PMID- 19378327
TI  - The use of vascularized fibular grafts for the reconstruction of spinal and
      sacral defects.
AB  - BACKGROUND: Large segmental defects of the spine may result from tumor resection
      as well as infection. The surrounding soft tissue in these situations is often
      compromised due to radiation exposure or infection. In these situations, in which
      conventional bone grafting has often failed, we have found vascularized fibular
      grafts an effective method of achieving bony union. The purpose of this study was
      to review the results of vascularized bone grafting for complex spinal
      reconstruction using free fibular transfer. METHODS: We performed a retrospective
      chart review of all patients who underwent multisegmental spinal reconstruction
      and pelvic reconstruction using posterior instrumentation and free fibula
      vascularized bone transfer. RESULTS: Twelve patients underwent 14 free fibula
      transfers (7 anterior and 5 posteriorly placed) for reconstruction of lumbosacral
      spinal defects. Preoperative diagnoses included tumor, osteomyelitis, and
      nonunion. Average number of vertebral body resections was four and posterior
      instrumentation was used for all arthrodeses. Average duration of follow up was
      45 months. Two flaps failed (14%), one resulting in nonunion and the other
      required salvage with an external hemipelvectomy. All remaining flaps healed at a
      mean time of 4.5 months (range, 3-10 months). CONCLUSION: Free fibula transfer
      for complex spinal reconstruction is a reliable means of obtaining bony union for
      complex lumbar or sacral resections where traditional bone grafting techniques
      may not be technically feasible.

PMID- 19378328
TI  - Correlation of three sciatic functional indices with histomorphometric findings
      in a rat sciatic nerve allograft repair model.
AB  - Walking track analysis was used to measure global functional recovery following
      sciatic nerve injury. The correlation of morphologic outcome and different
      sciatic functional indices (SFIs) depends on different variables. The objective
      of this study was to compare three different SFIs and their correlation with
      histomorphometric findings in a sciatic nerve allograft repair model in the rat
      without (group I, n = 8) or with (group II, n = 8) daily intramuscular
      administration of 0.1 mg/kg FK 506. The correlation of SFIs with each other and
      with the myelin basic protein (MBP) density of nerve sections proximal, median,
      and distal to sciatic nerve grafts (1.5 cm) at 4, 8, 12, and 16 weeks
      postoperation (p.o.) was calculated, and unoperated animals served as controls (n
      = 8). Significant differences between SFIs calculated for experimental groups I
      and II at 12 and 16 weeks p.o. suggested that superior functional nerve recovery
      occurred in group II. However, there were significant differences between all
      SFIs at 16 weeks p.o. in group II, whereas only differences between SFI 1 and SFI
      2 + 3 occurred in group I. SFIs of group II did not reach the values of the
      unoperated group. There were significant differences between the
      histomorphometric outcomes of groups I and II. There was no significant
      difference of MBP density between group II and the unoperated group, suggesting
      complete morphologic recovery. In conclusion, we found significant correlation
      between the MBP densities of groups I and II and all SFIs, suggesting a close
      relationship between histomorphometric and functional findings. (c) 2009 Wiley
      Liss, Inc. Microsurgery, 2009.

PMID- 19378329
TI  - Vascularized free fibular bone graft in the management of congenital tibial
      pseudarthrosis.
AB  - Congenital pseudarthrosis of the tibia (CPT) remains one of the most challenging
      problems confronting the orthopaedic surgeon. The operative results are
      frequently less than successful; many cases require several surgical procedures,
      and a significant number of them ending in amputation. The purpose of this study
      was to access the surgical results, complications, secondary procedures, and long
      term results of free vascularized fibular graft (FVFG) in the treatment of
      congenital pseudarthrosis of the tibia. Between 1992 and 2007, nine patients with
      CPT were treated consecutively at our clinic with free fibula transfer. There
      were six females and three males. The mean age at the time of operation was 6.5
      years (range, 1-12 years). Stability, after reconstruction with FVFG, was
      maintained with internal fixation in five patients, unilateral frame external
      fixation in three patients, and intramedullary pin in one patient. Average
      postoperative follow-up time was 9 years (range, 2-15 years). In seven patients,
      both ends of the graft healed primarily within 3.7 months (range, 1.5-6 months).
      In one patient, the distal end of the graft did not unit. This patient required
      three subsequent operations to achieve union. Stress fracture occurred in the
      middle of the grafted fibula in one patient, who underwent four additional
      operations before union, was achieved. Despite the relatively high-complication
      rate, FVFG remains a valid method for the treatment of CPT. However, even
      achieving union of pseudarthrosis is not enough for the resolution of the
      disease. This is only half of the problem; the other half is to maintain union.
      Long-term follow-up beyond skeletal maturity, if possible, is necessary to
      evaluate surgical results.

PMID- 19378330
TI  - Epidemic of plurality and contributions of assisted reproductive technology
      therein.
AB  - A commentary on contributions of ART to the pandemic of multiple gestations is
      presented and mechanistic aspects therein are explored.

PMID- 19378331
TI  - Twinning on the brain: the effect on neurodevelopmental outcomes.
AB  - Twinning is currently considered a complex multifactorial trait. Few studies have
      explored how the unique genetic and environmental influences that create twinning
      affect phenotypes and outcomes. Previous data has shown that twins account for a
      significant proportion of preterm and low-birth-weight infants, who are at risk
      for long-term neurodevelopmental disabilities such as cerebral palsy and
      cognitive impairment. More recently, it has been postulated that even without
      these co-morbidities, twinning in and of itself may incur a neurodevelopmental
      disadvantage even among term newborns. The purpose of this review is to report
      primarily on neuromotor outcomes of twins compared to singletons. In addition, we
      describe specific environmental risk factors among twins which are associated
      with poorer outcomes. Several putative neurodevelopmental modulators are
      explored, including death of a co-twin, chorionicity, birth weight discordance,
      and twin-twin transfusion. By teasing out environmental influences that
      potentially influence neurocognitive outcomes, families can receive more specific
      counseling and developmental services can be provided to those twins at
      especially high risk.

PMID- 19378332
TI  - Genetic drift. Two miracles, one year later.

PMID- 19378333
TI  - Clinical significance of chimerism.
AB  - Twins have been previously classified as either monozygotic or dizygotic. In
      recent years, fascinating, non-traditional mechanisms of twinning have been
      uncovered. We define chimerism versus mosaicism, touch on chimerism in the animal
      world, and explain timing of chimerism in humans. In addition, we discuss when to
      suspect chimerism in patients, and how to proceed with diagnostic evaluation and
      confirmation.

PMID- 19378334
TI  - Not really identical: epigenetic differences in monozygotic twins and
      implications for twin studies in psychiatry.
AB  - Classical twin studies in the field of psychiatry generally fall into one of two
      categories: (1) those designed to identify environmental risk factors causing
      discordance in monozygotic (MZ) twins and (2) those geared towards identifying
      genetic risk factors. However, neither environment nor differences in DNA
      sequence can fully account for phenotypic discordance among MZ twins. The field
      of epigenetics--DNA modifications that can affect gene expression--offers new
      models to understand discordance in MZ twins. In the past, MZ twins were regarded
      as genetically-identical controls for differing environmental conditions. In
      contrast, the evolving current concept is that epigenetic differences between MZ
      twins may modulate differences in diverse phenotype, from disease to personality.
      In this article, we review some twin studies, and discuss the dynamic
      interactions between stochastic, environmental, and epigenetic variables that
      influence neurobiological phenotypes.

PMID- 19378335
TI  - Selective inhibition of proliferation in colorectal carcinoma cell lines
      expressing mutant APC or activated B-Raf.
AB  - Tumor-derived cell lines are indispensable tools for understanding the
      contribution of activated signaling pathways to the cancer phenotype and for the
      design and testing of targeted signal therapies. In our study, we characterize 10
      colorectal carcinoma cell lines for the presence of mutations in the wnt,
      Ras/MAPK, PI3K and p53 pathways. The mutational spectrum found in this panel of
      cell lines is similar to that detected in primary CRC, albeit with higher
      frequency of mutation in the beta-catenin and B-Raf genes. We have monitored
      activation of the wnt and Ras/MAPK pathways in these cells and analyzed their
      sensitivity to selective signaling inhibitors. Using beta-catenin subcellular
      distribution as a marker, we show that cells harboring APC mutations have low
      level activated wnt signaling, which can be blocked by the extracellular wnt
      inhibitor DKK-1, suggesting autocrine activation of this pathway; proliferation
      of these cells is also blocked by DKK-1. In contrast, cells with beta-catenin
      mutations are unresponsive to extracellular wnt inhibition. Constitutive
      phosphorylation of MAPK is present in the majority of the cell lines and
      correlates with B-Raf but not K-Ras mutations; correspondingly, the proliferation
      of cells harboring mutations in B-Raf, but not K-Ras, is exquisitely sensitive
      inhibition of the MAPK pathway. We find no correlation between PI3K mutation or
      loss of PTEN expression and increased sensitivity to PI3K inhibitors. Our study
      discloses clear-cut differences in responsiveness to signaling inhibitors between
      individual mutations within an activated signaling pathway and suggests likely
      targets for signal-directed therapy of colorectal carcinomas.

PMID- 19378336
TI  - Identification of novel microRNA targets based on microRNA signatures in bladder
      cancer.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate protein
      coding genes. To identify miRNAs that have a tumor suppressive function in
      bladder cancer (BC), 156 miRNAs were screened in 14 BCs, 5 normal bladder
      epithelium (NBE) samples and 3 BC cell lines. We identified a subset of 7 miRNAs
      (miR-145, miR-30a-3p, miR-133a, miR-133b, miR-195, miR-125b and miR-199a*) that
      were significantly downregulated in BCs. To confirm these results, 104 BCs and 31
      NBEs were subjected to real-time RT-PCR-based experiments, and the expression
      levels of each miRNA were significantly downregulated in BCs (p < 0.0001 in all).
      Receiver-operating characteristic curve analysis revealed that the expression
      levels of these miRNAs had good sensitivity (>70%) and specificity (>75%) to
      distinguish BC from NBE. Our target search algorithm and gene-expression
      profiling in BCs (Kawakami et al., Oncol Rep 2006;16:521-31) revealed that
      Keratin7 (KRT7) mRNA was a common target of the downregulated miRNAs, and the
      mRNA expression levels of KRT7 were significantly higher in BCs than in NBEs (p =
      0.0004). Spearman rank correlation analysis revealed significant inverse
      correlations between KRT7 mRNA expression and each downregulated miRNA (p <
      0.0001 in all). Gain-of-function analysis revealed that KRT7 mRNA was
      significantly reduced by transfection of 3 miRNAs (miR-30-3p, miR-133a and miR
      199a*) in the BC cell line (KK47). In addition, significant decreases in cell
      growth were observed after transfection of 3 miRNAs and si-KRT7 in KK47,
      suggesting that miR-30-3p, miR-133a and miR-199a* may have a tumor suppressive
      function through the mechanism underlying transcriptional repression of KRT7.

PMID- 19378337
TI  - MFM/geneticist view on prenatal management of twins.
AB  - Twin pregnancies are associated with an increase in both fetal and maternal
      morbidity and mortality. Health care supervision is complex, increasingly
      requiring care from maternal-fetal medicine specialists. This review discusses
      optimal twin prenatal management, which includes recognizing increased twin
      pregnancy risks specific to twin-types; counseling families regarding fetal
      complications, ranging from prematurity to cerebral palsy; screening for
      aneuploidy and open neural tube defects; specific twin guidelines for diagnostic
      testing, including chorionic villus sampling and amniocentesis; and monitoring
      for maternal complications.

PMID- 19378338
TI  - NF-kappaB inhibition triggers death of imatinib-sensitive and imatinib-resistant
      chronic myeloid leukemia cells including T315I Bcr-Abl mutants.
AB  - The Bcr-Abl inhibitor imatinib is the current first-line therapy for all newly
      diagnosed chronic myeloid leukemia (CML). Nevertheless, resistance to imatinib
      emerges as CML progresses to an acute deadly phase implying that
      physiopathologically relevant cellular targets should be validated to develop
      alternative therapeutic strategies. The NF-kappaB transcription factor that
      exerts pro-survival actions is found abnormally active in numerous hematologic
      malignancies. In the present study, using Bcr-Abl-transfected BaF murine cells,
      LAMA84 human CML cell line and primary CML, we show that NF-kappaB is active
      downstream of Bcr-Abl. Pharmacological blockade of NF-kappaB by the IKK2
      inhibitor AS602868 prevented survival of BaF cells expressing either wild-type,
      M351T or T315I imatinib-resistant mutant forms of Bcr-Abl both in vitro and in
      vivo using a mouse xenograft model. AS602868 also affected the survival of LAMA84
      cells and of an imatinib-resistant variant. Importantly, the IKK2 inhibitor
      strongly decreased in vitro survival and ability to form hematopoietic colonies
      of primary imatinib resistant CML cells including T315I cells. Our data strongly
      support the targeting of NF-kappaB as a promising new therapeutic opportunity for
      the treatment of imatinib resistant CML patients in particular in the case of
      T315I patients. The T315I mutation escapes all currently used Bcr-Abl inhibitors
      and is likely to become a major clinical problem as it is associated with a poor
      clinical outcome.

PMID- 19378339
TI  - Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers.
AB  - Missense somatic mutations in IDH1 gene affecting codon 132 have recently been
      reported in glioblastoma multiforme (GBM) and other gliomas. The recurrent nature
      of the IDH1 mutations in the same amino acid strongly suggests that the mutations
      may play important roles in the pathogenesis of glial tumors. The aim of this
      study was to see whether the IDH1 codon 132 mutations occur in other human
      cancers besides glial tumors. We also attempted to confirm the occurrence of the
      IDH1 mutations in GBM of Korean patients. We have analyzed 1,186 cancer tissues
      from various origins, including carcinomas from breast, colon, lung, stomach,
      esophagus, liver, prostate, urinary bladder, ovary, uterine cervix, skin and
      kidney, and malignant mesotheliomas, primary GBM, malignant meningiomas, multiple
      myelomas and acute leukemias by single-strand conformation polymorphism analysis.
      We found four IDH1 codon 132 mutations in the GBM (4/25; 16.0%), two in the
      prostate carcinomas (2/75; 2.7%) and one in the B-acute lymphoblastic leukemias
      (B-ALL) (1/60; 1.7%), but none in other cancers. The IDH1 mutations consisted of
      five p.R132H and two p.R132C mutations. The data indicate that IDH1 codon 132
      mutations occur not only in GBM, but also in prostate cancers and B-ALL. This
      study suggests that despite the infrequent incidence of the IDH1 mutations in
      prostate cancers and B-ALL, mutated IDH1 could be therapeutically targeted in
      these cancers and in glial tumors with the IDH1 mutations.

PMID- 19378341
TI  - Interferon-gamma reverses the immunosuppressive and protumoral properties and
      prevents the generation of human tumor-associated macrophages.
AB  - Tumor-associated macrophages (TAM) are M2d-polarized cells (IL-10(high), IL
      12(low), ILT3(high), CD86(low)) that accumulate in tumor microenvironment. TAM
      inhibit antitumor T lymphocyte generation and function, contribute to tumor
      tolerance and are trophic for tumors. In this study, we investigated whether some
      immunological factors may reverse TAM immunosuppressive properties. Among 32
      cytokines, we have identified IFNgamma on its ability to switch immunosuppressive
      TAM into immunostimulatory cells. Upon IFNgamma exposure, TAM purified from
      ovarian cancer ascites recover a M1 phenotype (IL-10(low), IL-12(high)), express
      high levels of CD86 and low levels of ILT3, enhance the proliferation of CD4(+) T
      lymphocytes and potentiate the cytotoxic properties of a MelanA-specific CD8(+) T
      cell clone. IFNgamma-treated TAM also secreted reduced levels of mediators
      promoting suppressive T cell accumulation (CCL18) and trophic for tumors (VEGF
      and MMP9). As TAM derive from the local differentiation of peripheral blood
      monocytes, we investigated whether IFNgamma may also affect TAM generation. In
      the presence of ovarian ascites, IFNgamma skewed monocyte differentiation from
      TAM-like cells to M1-polarized immunostimulatory macrophages. Together, these
      data show that IFNgamma overcomes TAM-induced immunosuppression by preventing TAM
      generation and functions. These data highlight that IFNgamma used locally at the
      tumor site could potentiate the efficacy of antitumor immunotherapies based on
      the generation of effector T cells.

PMID- 19378340
TI  - Lifetime and baseline alcohol intake and risk of cancer of the upper aero
      digestive tract in the European Prospective Investigation into Cancer and
      Nutrition (EPIC) study.
AB  - Recent alcohol consumption is an established risk factor for squamous cell
      carcinoma (SCC) of the upper aero-digestive tract. In contrast, the role of
      lifetime exposure to alcohol with regard to risk of SCC is not well established.
      Historical data on alcohol use are available in 271,253 participants of the
      European Prospective Investigation into Cancer and Nutrition (EPIC). During
      2,330,381 person years, 392 incident SCC cases (279 men and 113 women) were
      identified. Cox regression was applied to model sex-specific associations between
      lifetime alcohol intake and SCC risk adjusting for potential confounders
      including smoking. Compared to men who drank 0.1-6.0 g/day alcohol at lifetime,
      the relative risks (RR) for developing SCC were significantly increased for men
      who drank 30.1-60.0 g/day (RR 1.65, 95% confidence interval:1.00-2.71), 60.1-96.0
      g/day (RR 2.20, 95%CI 1.23-3.95), and >96.0 g/day, (RR 4.63, 95% CI 2.52-8.48),
      and for former drinkers (RR 4.14, 95%CI 2.38-7.19). These risk estimates did not
      considerably change when baseline alcohol intake was analyzed. Compared to women
      who drank 0.1-6.0 g/day alcohol intake at lifetime, the RR were significantly
      increased for women who drank >30 g/d (RR 6.05, 95%CI 2.98-12.3). Applying
      similar categories, the relative risk for baseline alcohol intake was 3.26 (95%CI
      1.82-5.87). We observed a stronger association between alcohol intake at lifetime
      and risk of SCC in women compared to men (p for interaction = 0.045). The strong
      dose-response relation for lifetime alcohol use underscores that alcohol is an
      important risk factor of SCC of the upper aero-digestive tract throughout life.

PMID- 19378342
TI  - Micro-fabrication and monitoring of three-dimensional microstructures based on
      laser-induced thermoplastic formation.
AB  - This article reports a novel laser-induced micro-fabrication method and its
      monitoring system for three-dimensional (3D) microstructures. The mechanism of
      the method is that a small zone of thermoplastic material melted by laser heating
      grows in liquid surrounding environment, solidifying into a convex
      microstructure, such as micro-dot or micro-pillar. A laser diode (808 nm) with
      maximum power output of 130 mW is used as power source, and a kind of paraffin
      mixed with stearic acid and paint serves as the thermoplastic material for 3D
      microstructure formation experiments. A light microscope system consisting of a
      charge-coupled device (CCD) and a computer is utilized to realize real-time
      observation of the micro-fabricating process. The distribution of local
      temperature rise on material surface created by laser irradiation is simulated.
      The effects of liquid environment on microstructure formation have been
      theoretically analyzed and experimentally studied. Experiments are further
      carried out to investigate the relationship between laser spot and fabricated
      microstructures. The results indicate that the widths of micro-dots or micro
      pillars are mostly determined by the size of focal spot, and their heights
      increase with the enlargement of laser power density. With this method, a micro
      dot array of Chinese characters meaning "China" has been successfully fabricated
      through computer programming. This method has the advantages of implementing
      direct, mask-less, real-time and inexpensive 3D microstructure fabrication.
      Therefore, it would be widely applied in the fields of micro/nano-technology for
      practical fabrication of different kinds of 3D microstructures.

PMID- 19378343
TI  - Ultrastructural analysis of radicular dentine surface submitted to CO2 laser at
      different parameters.
AB  - BACKGROUND: There are no reported studies comparing different parameter settings
      of the CO(2) laser and irradiation direction considering their effect on the
      morphology of radicular dentine surface. PURPOSE: To evaluate the alterations of
      radicular dentine (cervical, middle, and apical thirds) irradiated with CO(2)
      laser at different potencies and irradiation directions. STUDY DESIGN: Roots of
      35 canines were prepared and randomly distributed according to the laser potency:
      GI: no laser treatment (control) (n = 5); GII, 2 W (n = 10); GIII: 4 W (n = 10);
      GIV: 6 W (n = 10). Each group (excepting GI) was divided in two subgroups
      according to the irradiation distance (n = 5): (A) parallel and (B) perpendicular
      to the root canal walls. The roots were splited longitudinally and analyzed by
      scanning electron microscopy in a qualiquatitative way. The scores were submitted
      to Kruskal-Wallis and Dunn's tests. RESULTS: No significant statistical
      differences were observed among root canal thirds (P > 0.05). The specimens
      irradiated with 2 W were statistically different (P < 0.05) from those irradiated
      with 4 and 6 W, which were statistically similar between themselves (P > 0.05).
      With 2, 4, and 6 W at in parallel irradiation and 2 W in perpendicular direction,
      the surface showed a fissured aspect. With 4 W in perpendicular direction and 6 W
      in parallel and perpendicular direction, surface was modified by laser action and
      exhibited fused areas. CONCLUSIONS: The intensity of the effects is dependent on
      the laser-irradiation dosimetries. Alterations were more intense when higher
      parameters were used.

PMID- 19378344
TI  - Role of adenosine monophosphate-activated protein kinase-p70 ribosomal S6 kinase
      1 pathway in repression of liver X receptor-alpha-dependent lipogenic gene
      induction and hepatic steatosis by a novel class of dithiolethiones.
AB  - Dithiolethiones, a novel class of adenosine monophosphate-activated protein
      kinase (AMPK) activators, prevent insulin resistance through AMPK-dependent p70
      ribosomal S6 kinase-1 (S6K1) inhibition. There is no known effect of S6K1 for
      liver X receptor-alpha (LXRalpha)-mediated lipogenic gene expression and
      steatosis, a cause of chronic liver disease. This study investigated the role of
      S6K1 in LXRalpha activation and the effects of oltipraz (prototype) and other
      dithiolethiones on LXRalpha-dependent lipogenesis in hepatocytes and high-fat
      diet animal model. Oltipraz prevented the ability of LXRalpha agonist (T0901317)
      to activate sterol regulatory element binding protein-1c (SREBP-1c), inhibiting
      its own mRNA and protein induction. Impaired SREBP-1c activity by oltipraz caused
      inhibition of LXRalpha-induced transcription of the fatty acid synthase,
      LXRalpha, acetyl-CoA carboxylase, stearoyl-CoA desaturase-1, and adenosine
      triphosphate-binding cassette transporter A1 genes. S6K1 activation antagonized
      the inhibitory effect of oltipraz on SREBP-1c activation, whereas dominant
      negative (DN) mutant S6K1 and rapamycin inhibited the T0901317-induced SREBP-1c
      expression. Oltipraz impaired LXRalpha DNA binding activity and LXR agonist
      induced CYP7A1-LXRE-luciferase (CYP7A1) transactivation. Moreover, in vitro S6K1
      directly phosphorylated LXRalpha at serine residues for gene transactivation,
      which was antagonized by its DN mutant. S6K1 inhibition antagonized CYP7A1
      induction promoted by AMPK inhibition, whereas AMPK activation abrogated S6K1
      dependent CYP7A1 induction, supporting the opposing role of S6K1 and AMPK in LXR
      activity. Finally, oltipraz was found to inhibit hepatic triglyceride
      accumulation and lipogenic gene induction in mice fed a high-fat diet. Other
      dithiolethiones also inhibited SREBP-1c induction by T0901317. CONCLUSION: Our
      findings showing the role of AMPK-S6K1 pathway in LXR activity and S6K1-dependent
      inhibition of LXRalpha-induced lipogenic gene transactivation by a novel class of
      dithiolethiones led to the identification of S6K1 as a particularly attractive
      target for intervention in hepatic steatosis.

PMID- 19378345
TI  - Long-term outcome of hepatitis B e antigen-negative hepatitis B surface antigen
      carriers in relation to changes of alanine aminotransferase levels over time.
AB  - The baseline alanine aminotransferase (ALT) level was reported to have prognostic
      value in chronic hepatitis B virus (HBV) infection, during which ALT may change
      over time. Instead of baseline ALT, this study aimed to study the prognostic
      value of the height of ALT during the course of chronic HBV infection. A total of
      4376 asymptomatic hepatitis B e antigen (HBeAg) negative, surface antigen (HBsAg)
      carriers with baseline ALT less than 2 times the upper limit of normal (ULN) were
      monitored with ALT measurement and ultrasonography every 3 to 12 month for over 3
      years. Maximal ALT levels during follow-up were correlated with long-term
      outcomes using morbidity and mortality data from hospital records, cancer
      registration, and national mortality database. Baseline ALT level was normal in
      3673 subjects and increased to abnormal level in 1720 (46.8%) during a mean
      follow-up period of 13.4 +/- 5.2 (3.0-28.7) years. The incidence of liver
      cirrhosis, hepatocellular carcinoma (HCC), and mortality increased with
      increasing maximal ALT level during follow-up, especially in those with maximal
      ALT of at least 2 times ULN, as compared with those who maintained normal ALT.
      Cox regression analysis indicated that age at entry, sex, and maximal ALT level
      during follow-up were significant independent factors associated with the
      development of cirrhosis, HCC, and mortality whereas cirrhosis was also an
      independent factor for HCC development and mortality. CONCLUSION: Persistently
      normal ALT was associated with excellent long-term prognosis, whereas increasing
      ALT levels of at least 2 times ULN during follow-up was associated with
      increasing morbidity and mortality. ALT of at least 2 times ULN is therefore an
      appropriate threshold for anti-HBV therapy, whereas those with ALT 1 to 2 times
      ULN require liver biopsy for decision.

PMID- 19378346
TI  - Mental capacity to consent to treatment and admission decisions in older adult
      psychiatric inpatients.
AB  - OBJECTIVES: There is little information about older adult psychiatric inpatients'
      capacity to consent to clinical decisions. In younger adults, lack of capacity is
      associated with poor insight and psychosis rather than cognitive impairment. We
      assessed the prevalence and predictors of mental capacity to make treatment and
      admission decisions in older psychiatric inpatients, and asked their views about
      who should make these decisions. METHODS: We interviewed 99 participants using
      the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) in three
      geographical locations. RESULTS: Fifty-two (52.5%) participants had capacity for
      admission and 38 (38.4%) for treatment decisions. Capacity was associated with
      not having dementia, and higher levels of insight and cognition. Those with
      depression were more likely to have capacity than those with psychosis. 75% of
      patients without capacity for admission were not detained legally. CONCLUSIONS:
      Patients can have capacity to make decisions in one area but not in others. Many
      people are admitted and treated in a way that is contrary to the human rights
      legislation. The new Deprivation of Liberty Safeguards in England and Wales are
      likely to apply to a significant proportion of older inpatients. Most people
      wanted doctors to make treatment and admission decisions and very few wanted
      their family to make decisions on their behalf.

PMID- 19378347
TI  - Extreme weight change behaviours: are overweight and normal weight adolescents
      different, and does this vary over time?
AB  - This study examined the nature of extreme weight loss behaviours among overweight
      and normal weight adolescents. Body mass index (BMI), body dissatisfaction, body
      importance, pubertal timing, negative affect, bulimic symptoms, food supplements
      and exercise dependence were evaluated at Time 1 and 16 months later at Time 2
      among 788 adolescents. There were a large number of differences in the strategies
      adopted by overweight adolescents, and these remained relatively stable over
      time. In addition, girls engaged in more bulimic symptoms than boys; particularly
      overweight girls. Negative affect was also a major predictor of health risk
      behaviours for overweight adolescent boys and girls. Implications of these
      findings for the treatment of extreme weight loss behaviours among overweight
      adolescents are discussed.

PMID- 19378348
TI  - An approach to sub-grouping the eating disorder population: adding attachment and
      coping style.
AB  - OBJECTIVE: To investigate whether clinically meaningful sub-groups of patients
      can be identified by clustering eating disorder features, attachment and coping
      styles. METHOD: 165 patients completed the Eating Disorder Examination (EDE),
      Attachment Style Questionnaire (ASQ) and Utrecht Coping List (UCL). Cluster
      analysis was used to identify sub-groups across the sample. RESULTS: Four
      clusters were identified. Cluster one had low levels of eating disorder
      behaviours and the most severe attachment and coping difficulties. Cluster two
      had high levels of dietary restriction and exercise, and a fearful/avoidant
      attachment style. Cluster three had high levels of binge eating and vomiting, and
      few attachment and coping difficulties. Cluster four had low levels of eating
      disorder features and positive attachment and coping styles. CONCLUSIONS:
      Clustering participants on the basis of eating disorder features, attachment and
      coping yields four sub-groups appearing to have clinical face validity.

PMID- 19378349
TI  - Risk and protective factors for disturbed eating in adolescent girls - aspects of
      perfectionism and attitudes to eating and weight.
AB  - The aim of this study was to longitudinally examine the role of personal
      standards, self-evaluation, perceived benefits of thinness and attitudes to
      eating and weight in the development of healthy versus disturbed eating in
      adolescent girls. In a longitudinal study, girls who participated in two
      assessments, four to five years apart, were divided into three groups according
      to the attitudes to eating that they manifested at the second evaluation: those
      with disturbed eating patterns (DE-group, n = 49), those with intermediate
      concerns about eating (IE-group, n = 260) and those with healthy eating attitudes
      (HE-group, n = 120). Variables concerning attitudes to eating and weight and
      physical self-evaluation emerged as risk factors, whereas personal standards or
      self-evaluation in general did not. Protective factors were a low BMI, healthy
      eating attitudes, an accepting attitude towards body size and a positive self
      evaluation, particularly with regard to physical and psychological
      characteristics. The results of this study contribute to the understanding of
      early risk and protective factors for eating disturbances in girls.

PMID- 19378350
TI  - Modulation of protein-ligand interactions by photocleavage of a cyclic peptide
      using phosphatidylinositol 3-kinase SH3 domain as model system.
AB  - To photomodulate the interaction of the phosphatidylinositol 3-kinase SH3 domain
      with a peptide ligand, a cyclic peptide (cyclic-1) with a photolabile side chain
      to-side chain linker was synthesized. The conformation of cyclic-1 differs from
      that of the parent linear peptide, but becomes identical by UV-irradiation.
      Accordingly, the binding affinity of cyclic-1 to the SH3 domain increased upon
      conversion of the cyclic to a linear flexible structure by irradiation (K(d): 3.4
      +/- 1.7 and 0.9 +/- 0.3 mM, respectively). These results confirm the usefulness
      of a photocleavable peptide for photocontrol of peptide-protein interactions.

PMID- 19378351
TI  - The Norwegian version of the Mini-Mental Adjustment to Cancer Scale: factor
      structure and psychometric properties.
AB  - OBJECTIVE: The object of the study was to examine the factor structure and the
      psychometric properties of the Mini-Mental Adjustment to Cancer Scale (Mini-MAC)
      among a large sample of Norwegian breast cancer patients. METHODS: A total of 402
      patients with breast cancer completed the Mini-MAC. RESULTS: Principal component
      analysis with varimax rotion confirmed four factors. Three had psychometric
      properties to the original Mini-MAC Helpless-Hopeless (HH), Anxious Preoccupation
      (AP) and Cognitive Avoidance (CA) subscales. The fourth, named Positive Attitude
      (PA) combined the Fighting Spirit (FS) and the Fatalism subscales of the original
      Mini-MAC. Construct validities were assessed by examining the interscale
      correlations as well as the correlations between the Mini-MAC subscales and the
      HADS subscales scores. Internal consistency of the five subscales was
      satisfactory for the original (HH, AP, CA, FA, coefficients=0.60-0.83), except
      for the FS subscale (coefficient=21). CONCLUSION: In view of the low internal
      reliability for the Norwegian Mini-MAC FS subscale coefficient; it appears to be
      more appropriate to use the Norwegian Mini-MAC as a four-factor model. If
      researcher or clinicians in Norway use the five-factor model, they should take
      great care when interpreting the fighting spirit subscale.

PMID- 19378352
TI  - A DFT and AIM analysis of the spin-spin couplings across the hydrogen bond in the
      2-fluorobenzamide and related compounds.
AB  - In 1975 a large number of coupling constants were measured in 2-fluorobenzamide
      labeled with (15)N. Some of them were assigned to couplings through
      intramolecular N-H...F hydrogen bonds (HBs). These couplings change dramatically
      when CDCl(3) is replaced by DMSO-d(6). In this theoretical paper we provide
      density functional theory (DFT) calculations that justify the existence of a weak
      HB in the absence of solvent, while solvents that act as HB acceptors break down
      the intramolecular hydrogen bond (IMHB) of 2-fluorobenzamide. Atoms in molecules
      (AIM) analyses and Steiner-Limbach plots were used to analyze the structure of
      the compounds.

PMID- 19378353
TI  - Non-parametric methods for cost-effectiveness analysis: the central limit theorem
      and the bootstrap compared.
AB  - Cost-effectiveness analyses (CEA) alongside randomised controlled trials commonly
      estimate incremental net benefits (INB), with 95% confidence intervals, and
      compute cost-effectiveness acceptability curves and confidence ellipses. Two
      alternative non-parametric methods for estimating INB are to apply the central
      limit theorem (CLT) or to use the non-parametric bootstrap method, although it is
      unclear which method is preferable. This paper describes the statistical
      rationale underlying each of these methods and illustrates their application with
      a trial-based CEA. It compares the sampling uncertainty from using either
      technique in a Monte Carlo simulation. The experiments are repeated varying the
      sample size and the skewness of costs in the population. The results showed that,
      even when data were highly skewed, both methods accurately estimated the true
      standard errors (SEs) when sample sizes were moderate to large (n>50), and also
      gave good estimates for small data sets with low skewness. However, when sample
      sizes were relatively small and the data highly skewed, using the CLT rather than
      the bootstrap led to slightly more accurate SEs. We conclude that while in
      general using either method is appropriate, the CLT is easier to implement, and
      provides SEs that are at least as accurate as the bootstrap.

PMID- 19378354
TI  - Systematic reviews of economic evaluations: utility or futility?
AB  - Systematic reviews of studies of effectiveness are the centrepiece of evidence
      based medicine and policy making. Increasingly, systematic reviews of economic
      evaluations are also an expected input into much evidence-based policy making,
      with some health economists even calling for 'an economics approach to systematic
      review'. This paper questions the value of conducting systematic reviews of
      economic evaluations to inform decision making in health care. It argues that the
      value of systematic reviews of economic evaluations is usually undermined by
      three things. Firstly, compared with effectiveness studies, there is a much wider
      range of factors that limit the generalisability of cost-effectiveness results,
      over time and between health systems and service settings, including the context
      dependency of resource use and opportunity costs, and different decision contexts
      and budget constraints. Secondly, because economic evaluations are more
      explicitly intended to be decision-informing, the requirements for
      generalisability take primacy, and considerations of internal validity become
      more secondary. Thirdly, since one of the two main forms of economic evaluation -
      decision analytic modelling - is itself a well-developed method of evidence
      synthesis, in most cases the need for a comprehensive systematic review of
      previous economic evaluations of a particular health technology or policy choice
      is unwarranted. I conclude that apparent 'meta-analytic expectations' for clear
      and widely applicable cost-effectiveness conclusions from systematic reviews of
      economic evaluations are optimistic and generally futile. For more useful
      insights and knowledge from previous economic studies in evidence-based policy
      making, a more limited range of reasons for conducting systematic reviews of
      health economic studies is proposed.

PMID- 19378355
TI  - Aspartic acid scaffold in bradykinin B1 antagonists.
AB  - Several novel bradykinin B1 receptor (B1R) antagonists were synthesized utilizing
      a new aspartic acid scaffold. This core is derived from the highly potent
      dihydroquinoxalinone scaffold published recently by researchers at Merck (Ha et
      al. Biochem. Biophys. Res. Commun. 2005, 331, 159-166). Despite the considerably
      limited chemical space of B1 antagonists, the synthesized compounds still showed
      significant biological activity. None of the four most potent compounds showed
      significant activity on the bradykinin B2 receptor (B2R), consequently they can
      be considered as valuable starting points for designing more potent and selective
      B1 antagonists. Furthermore, the synthesis of these aspartic acid derivatives is
      much simpler than that of the original Merck compounds suggesting efficient
      parallel synthesis approaches during their optimization. Docking known and novel
      B1 antagonists into the refined B1R homology model including the second
      extracellular loop (EC2) underlined the importance of this loop in ligand
      binding. Comparative binding mode analysis revealed that our novel compounds bind
      similar to the dihydroquinoxalinone template. Our results indicate that the rigid
      core of the dihydroquinoxalinone containing B1 antagonists is not crucial for
      maintaining B1 activity.

PMID- 19378356
TI  - Arthroscopic visualisation of the distal radioulnar joint.
AB  - The diagnosis of chronic wrist pain is challenging and wrist arthroscopy has been
      recognised as the "gold standard". The present study investigated the efficacy of
      adding distal radioulnar joint (DRUJ) arthroscopy to routine wrist arthroscopy.
      The records of 67 patients who underwent DRUJ arthroscopy were reviewed, and the
      success rates for visualisation of intra-articular structures were determined.
      Pathological findings were correlated with ulnar-side wrist pain. In seven
      patients, pre-operative diagnoses were altered after DRUJ arthroscopy. The ulnar
      head and proximal surface of the triangular fibrocartilage complex (TFCC) were
      visualised in 100% and 99% of patients, respectively, while the foveal insertion
      of TFCC and sigmoid notch were visualised in 57% and 69%, respectively.
      Pathological findings of the proximal surface of TFCC tended to relate to ulnar
      wrist pain (p = 0.06). DRUJ arthroscopy should be included in routine wrist
      arthroscopy to enhance the accuracy of diagnosis.

PMID- 19378357
TI  - Closed intramedullary fixation for metacarpal fractures using J-shaped nail.
AB  - The purpose of this study is to present the results of a new intramedullary
      fixation technique for metacarpal fractures. A J-shaped nail, which is a curved
      2.0 mm diameter Kirschner wire sharply bent at the proximal end, was inserted
      from the dorsal aspect of the metacarpal base. Twenty-one metacarpal fractures
      (five transverse shaft fractures and 16 neck fractures) in 19 hands of 18
      patients with were operated by this technique. All fractures had successful
      unions. Clinical and radiographic results were excellent in all ten hands that
      had excluded concomitant injuries. There was no mechanical irritation of the skin
      or extensor tendons in any patient. This intramedullary fixation technique is
      very useful for neck or transverse shaft fractures of the metacarpals without
      concomitant injuries such as severe soft tissue damage.

PMID- 19378358
TI  - A comparison of endoscopic and open trigger finger release.
AB  - The main complaint of the patients after an open trigger finger release is a
      discomfort at the incision site. In this prospective study, we compared the two
      consecutive groups of patients with trigger fingers. One was treated by an open
      approach and the other by the endoscopic release of the A1 pulley. Pre- and post
      operative evaluation at seven, 30 and 90 days showed a faster recovery from the
      discomfort with a faster return to daily and working activities, after the
      endoscopic procedure.

PMID- 19378359
TI  - Early functional improvement after a modified ligament reconstruction tendon
      interposition arthroplasty for thumb basal joint arthritis.
AB  - Many modifications to trapeziectomy have been proposed for the treatment of thumb
      basal joint arthritis. Their final outcomes have been discussed intensively,
      whereas functional changes in the early post-operative period have not been fully
      documented. The purpose of the present study is to evaluate an early functional
      change following our modified ligament reconstruction with tendon interposition
      (LRTI) arthroplasty. Nine patients (ten thumbs) were included in this study. Pain
      levels, strength, and mobility were assessed before and after surgery at
      intervals of two months. Pain level significantly improved at two months after
      surgery. Grip and pinch strengths had increased gradually after a temporal
      decrease at two-month follow-up, and were significantly stronger at six months
      after surgery. Palmar abduction improved significantly at six months after
      surgery, whereas opposition did not change significantly. A modified LRTI is an
      effective procedure in terms of early functional improvement of pain, strength,
      and mobility.

PMID- 19378360
TI  - Minimally invasive management of trans-scaphoid perilunate fracture-dislocations.
AB  - This retrospective study evaluates the functional and radiological results of a
      series of acute trans-scaphoid dorsal perilunate fracture-dislocations treated
      operatively by minimally invasive technique. Twenty-one patients had surgery
      performed by one of three surgeons between 1994 and 2006, and all cases involved:
      (1) closed reduction of the carpus; (2) closed reduction and percutaneous screw
      fixation of the scaphoid fracture; and (3) closed reduction and multiple
      Kirschner wire stabilisation of the carpal dissociation. Seventeen males and four
      females with an average age of 29 years were evaluated. Ninety five per cent of
      internally fixed scaphoid healed at a mean time of 16 weeks. Radiographic
      alignment of the carpus was satisfactory in 17 cases. The average Mayo wrist
      score was 80 with three excellent and two poor results. There was one patient
      with asymptomatic DISI deformity. Two patients had radiographic evidence of mid
      carpal arthritis. One patient with a scaphoid nonunion required surgical repair
      with bone grafting. The results of this study suggest that a minimally invasive
      technique for treating acute trans-scaphoid perilunate fracture-dislocations can
      be considered as an alternative to open approaches.

PMID- 19378361
TI  - Treatment of intraosseous ganglia and bone cysts of the carpal bones with
      injectable calcium phosphate bone cement.
AB  - This article documents the outcome of treatment of intraosseous ganglia and
      simple bone cysts of the carpal bones by curettage and injectable calcium
      phosphate bone cement (CPC) grafting. The patients consisted of five men and
      three women. One had a cystic lesion in the scaphoid, one in the hamate, and five
      in the lunate. Curettage of the lesions was performed, and CPC was injected into
      the cavity. Five patients were diagnosed with a ganglion and three with a simple
      bone cyst. Among the five patients with wrist pain, the pain disappeared
      completely in four. Radiographs showed apparent partial absorption of CPC in four
      patients and no absorption in other four. There were no recurrence of tumours and
      no other complications were encountered. We conclude that calcium phosphate bone
      cement is a useful material for repairing bone defect after curettage of an
      intraosseous ganglion or bone cyst of a carpal bone.

PMID- 19378362
TI  - Full-thickness skin grafting in pseudosyndactily with recessive dystrophic
      epidermolysis bullosa.
AB  - Two 17- and 11-year-old brothers appeared with mitten pseudosyndactily of both
      hands. They have been suffering from recessive dystrophic epidermolysis bullosa
      with recurrent cutaneous blister formation either spontaneously or due to minor
      trauma. Surgeries were performed to release and widen the first web space. Full
      thickness skin graft which was used to cover the resulting raw surface appears
      stable as normal skin to them. The two brothers have improvement in range of
      motion of their thumbs and index fingers.

PMID- 19378363
TI  - Aneurysm of the superficial palmar arch: a case report.
AB  - Aneurysms of the hand are uncommon lesions. The most common location is the ulnar
      artery. We present a case of a young female who consulted us for a hand mass with
      a history of trauma to the hand. Pre-operative arteriogram showed a superficial
      palmar arch aneurysm. The mass was excised and the arch was reconstructed using a
      reversed Y-shaped vein graft. Fourteen months after surgery, there was no
      recurrence of the aneurysm and the patient only reported occasional cold
      intolerance.

PMID- 19378364
TI  - Delayed rupture of extensor digitorum communis tendon following volar plating of
      distal radius fracture.
AB  - We present a case of delayed rupture of extensor digitorum communis tendon seven
      years after volar plating of distal radius fracture. Drill bit penetration during
      surgery and prominent screw tips into the fourth extensor compartment have a
      potential risk to damage the tendons. Careful and accurate use of internal
      fixation instruments is necessary to avoid this complication.

PMID- 19378365
TI  - Extensor carpi radialis longus avulsion: a literature review and case report.
AB  - Extensor Carpi Radialis Longus (ECRL) avulsion is a rare injury which follows
      resisted wrist hyperflexion. Treatment of this condition with open reduction and
      internal fixation is not previously described in the literature, and treatment
      with plaster immobilisation or k-wire fixation requires a prolonged period of
      immobilisation. We believe that open reduction and internal fixation of these
      fractures with early mobilisation will result in the best possible wrist
      function. We describe a sign to raise the index of suspicion for this injury: a
      palpable bone lump on the dorsum of the hand in the presence of wrist extensor
      pain or weakness after wrist hyperflexion injury is a sign of wrist extensor
      avulsion.

PMID- 19378366
TI  - Metastasis of gastric cancer to the fifth metacarpal bone.
AB  - We present a rare case of a 72-year-old woman who had a metastatic bone tumour on
      the fifth metacarpal of the left hand from gastric cancer. It had occurred in the
      patient, two years after subtotal gastrectomy and partial resection of a liver
      for advances gastric cancer with metastasis to the liver. A number of
      investigations and the needle biopsy confirmed the diagnosis of the metastatic
      malignant tumour of fifth metacarpal bone and an amputation was performed.
      Although our patient died 12 months after hand surgery, amputation was effective
      in providing relief from pain in the affected hand for the remainder of her life.
      It is necessary to consider rare acrometastasis to the hand if a patient
      complains of swelling and pain of the hand without a trigger if there is a
      history of malignancy, including gastric cancer.

PMID- 19378367
TI  - Acute carpal tunnel syndrome secondary to calcific tendinitis: case report.
AB  - Acute carpal tunnel syndrome (CTS) secondary to calcific deposition is rarely
      reported. In this article we describe a case of acute CTS in the dominant hand of
      a 94-year-old female patient secondary to calcific tendinitis within the carpal
      tunnel. Diagnosis was difficult clinically and radiologically. Urgent complete
      median nerve decompression led to a good clinical recovery.

PMID- 19378368
TI  - Mast cell versus cancer cell: who is in the trap?

PMID- 19378369
TI  - KRAS mutation in metastatic colorectal cancer and its impact on the use of EGFR
      inhibitors.
AB  - As with many malignancies, cytogenetic information has become increasingly
      important to the diagnosis and proper treatment of colorectal cancer. In
      particular, several recent studies have confirmed that KRAS is not only one of
      the most commonly mutated genes in colorectal cancer, but also essential to
      treatment decision-making. Several key studies have demonstrated that patients
      with mutant KRAS do not respond to treatment with epidermal growth factor
      inhibitors. This finding has several implications for clinicians who treat
      patients with metastatic colorectal cancer. The following monograph includes
      discussions on the key issues surrounding the integration of recent data on KRAS
      status into the care of patients with this disease.

PMID- 19378370
TI  - Peanut butter found to be the cause of Salmonella outbreak.

PMID- 19378371
TI  - Vicks Vapo-Rub--How dangerous for children?

PMID- 19378372
TI  - Stuttering--what predicts it?

PMID- 19378373
TI  - Updated immunization recommendations for children.

PMID- 19378374
TI  - Croup: which children are most likely to get it?

PMID- 19378375
TI  - Dealing with childhood anxiety.

PMID- 19378376
TI  - Product recalls. Recalls: Fisher-Price Simplicity's Rainforest Portable Play
      Yards...and Infantino Infant Rattles.

PMID- 19378377
TI  - Quantitative analysis of the loss of muscarinic receptors in various peripheral
      tissues in M1-M5 receptor single knockout mice.
AB  - BACKGROUND AND PURPOSE: To compare loss in binding to muscarinic receptor (mAChR)
      subtypes with their known functions, the total density of muscarinic receptors
      was measured in peripheral tissues from wild type (WT) and mAChR knockout (KO)
      mice. EXPERIMENTAL APPROACH: Binding parameters of [N-methyl-3H]scopolamine
      methyl chloride ([3H]NMS) were determined in 10 peripheral tissues of WT and M1
      M5 receptor KO mice. Competition between [3H]NMS and darifenacin (selective M3
      receptor antagonist) was also measured. KEY RESULTS: There was an extensive loss
      of [3H]NMS-binding sites (maximal number of binding sites, Bmax) in heart and
      smooth muscle from M2KO mice, compared with WT mice. Smooth muscle from M3KO mice
      also showed a moderate loss of Bmax. Bmax fell in pancreas and bladder of M4KO
      mice and in prostate in M1KO and M3KO mice. There was a large loss of Bmax in
      exocrine and endocrine glands of M3KO mice with a moderate decrease in M2KO mice.
      Darifenacin inhibited specific [3H]NMS binding in submandibular gland and bladder
      of WT, M2KO and M3KO mice. Ki (inhibition constant) values for darifenacin in the
      submandibular gland were the same in WT and M2KO mice but increased in M3KO mice.
      However, Ki values in bladder were decreased in M2KO mice and increased in M3KO
      mice. CONCLUSIONS AND IMPLICATIONS: Single mAChR KO mice exhibit a loss of mAChR
      in peripheral tissues that generally paralleled the reported loss of function.
      Quantitative analysis of data, however, also suggested that, in some instances,
      normal expression of a receptor subtype depended on expression of other subtypes.

PMID- 19378378
TI  - Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic
      properties in fasted and non-fasted mice.
AB  - BACKGROUND AND PURPOSE: Obesity is a severe health problem in the modernized
      world and understanding the central nervous mechanisms underlying food-seeking
      behaviour and reward are at the forefront of medical research. Cannabinoid
      receptors have proven an efficient target to suppress hunger and weight gain by
      their pharmacological inactivation. EXPERIMENTAL APPROACH: A standard fasted
      protocol and a novel long-term home-cage observation system with free-feeding
      animals were used to assess the feeding behaviour of mice treated with the CB1
      antagonist AM251. Similarly, the effects of the phytocannabinoid Delta9
      tetrahydrocannabivarin (Delta9-THCV), which behaves like a CB1 antagonist, were
      also determined in free-feeding animals. KEY RESULTS: AM251 suppressed food
      intake and weight gain in fasted and non-fasted animals. The suppression of food
      intake by AM251 (10 mg.kg-1) endured for a period of 6-8 h when administered
      acutely, and was continuous when injected for four consecutive days. Pure Delta9
      THCV also induced hypophagia and weight reduction at doses as low as 3 mg.kg-1.
      No rebound was observed on the following day with all drug groups returning to
      normal activity and feeding regimes. However, a Delta9-THCV-rich cannabis-extract
      failed to suppress food intake and weight gain, possibly due to residual Delta9
      tetrahydrocannabinol (Delta9-THC) in the extract. This Delta9-THC effect was
      overcome by the co-administration of cannabidiol. CONCLUSIONS AND IMPLICATIONS:
      The data strongly suggest (i) the long-term home-cage observation system is a
      sensitive and obesity-relevant tool, and (ii) the phytocannabinoid Delta9-THCV is
      a novel compound with hypophagic properties and a potential treatment for obesity

PMID- 19378379
TI  - Roles of purines in synaptic modulation evoked by hypercapnia in isolated spinal
      cord of neonatal rat in vitro.
AB  - BACKGROUND AND PURPOSE: The purine compounds, adenosine 5'-triphosphate (ATP) and
      adenosine, are known to accumulate in the extracellular space and to elicit
      various cellular responses during hypoxia/ischemia, whereas the roles of purines
      during hypercapnia are poorly understood. In this study, we examined the effects
      of various drugs affecting purine turnover on the responses to hypercapnia in the
      spinal cord. EXPERIMENTAL APPROACH: Electrically evoked reflex potentials were
      measured in an in vitro preparation of the isolated spinal cord of the neonatal
      rat by extracellular recording. Extracellular adenosine concentrations were
      assayed by high performance liquid chromatography (HPLC) methods. KEY RESULTS:
      Hypercapnia (20% CO2) depressed the reflex potentials, which were partially
      reversed by an adenosine A1 receptor antagonist, 8-cyclopentyl theophylline, but
      not by a P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'
      disulphonic acid. Exogenous adenosine and ATP also depressed the reflex
      potentials via adenosine A1 receptors. The hypercapnia-evoked depression was not
      reversed by inhibitors of gap junction hemichannels, anion channels, P2X7
      receptors or equilibrative nucleoside transporters, all of which might be
      involved in purine efflux pathways. The adenosine accumulation evoked by
      hypercapnia was not inhibited by tetrodotoxin, ethylene glycol-bis(beta-amino
      ethyl ether) tetraacetic acid (EGTA) or an ecto-ATPase inhibitor, ARL 67156.
      Homocysteine thiolactone, used to trap intracellular adenosine, significantly
      reduced extracellular adenosine accumulation during hypercapnia. CONCLUSIONS AND
      IMPLICATIONS: These results suggest that hypercapnia released adenosine itself
      from intracellular sources, using pathways different from the conventional
      exocytotic mechanism, and that this adenosine depressed spinal synaptic
      transmission via adenosine A1 receptors.

PMID- 19378380
TI  - Quality of life and substance use: concepts and recent tendencies.
AB  - PURPOSE OF REVIEW: Quality of life (QoL) has become an important clinical and
      research outcome in clinical drug and alcohol studies. Yet, further advancement
      in this field is hindered by the lack of a consensual definition of QoL in that
      often investigators use the constructs of health status and QoL interchangeably.
      This article reviews the conceptual definitions of QoL as a researchable
      construct. It also presents the most commonly used questionnaires to evaluate QoL
      in the context of substance use. RECENT FINDINGS: In the area of substance use
      research, the evaluation of QoL has been conducted mainly via generic
      instruments. Most of the studies reporting results of QoL measurements have
      obtained their data from opiate users receiving different treatment modalities at
      various healthcare agencies. Recent studies have used the Injection Drug User QoL
      Scale as a specific assessment tool. Specific QoL instruments have also been
      developed in the area of alcohol and nicotine dependence. SUMMARY: QoL is an
      important clinical and research outcome in the context of substance use. However,
      the indiscriminate use of nonspecific measurement tools may produce questionable
      results. A new generation of specific tools takes into particular consideration
      the life areas that have a greater influence on the QoL of substance users. It is
      hoped that the new impetus toward a specific QoL assessment in the context of
      substance use will promote further scientific advancement in this area.

PMID- 19378381
TI  - Health consequences of illegal drug use.
AB  - PURPOSE OF REVIEW: The aim of this article is to review recent research on the
      health consequences of illegal drug use and possible risk factors, with a
      particular focus on prospective evidence. RECENT FINDINGS: Mortality studies have
      revealed qualitative and quantitative changes in causes of death among heroin and
      injecting drug users (IDUs), probably due to increasing exposure to harm
      reduction programs, the introduction of highly active antiretroviral therapy
      (HAART), the aging of drug users, and rising concurrent use of illegal drugs and
      prescription drugs. For morbidity, nonfatal overdose is still one of the most
      important concerns; likewise the higher prevalence of hepatitis C among non-IDUs
      and hepatitis A, B, C coinfection. Cannabis use has been consistently reported to
      be associated with the emergence of psychotic symptoms, yet that seems not to be
      the case for anxiety and depressive disorders. Use of 3,4
      methylenedioxymethamphetamine (MDMA) has been linked with short-term negative
      effects on cognitive performance (i.e. visual memory). A series of longitudinal
      studies have shown enduring unfavorable effects of prenatal cocaine and marijuana
      exposure on children's physical, cognitive, and language development. SUMMARY:
      Prospective evidence on illegal drug use in particular subpopulations may be
      needed to better understand health problems among users at different life stages
      and the possible long-term effects.

PMID- 19378382
TI  - Akathisia and second-generation antipsychotic drugs.
AB  - PURPOSE OF REVIEW: Akathisa is one of the most common and distressing neuroleptic
      induced extrapyramidal side effects. Although it is well recognized in the
      context of conventional antipsychotic medications, there have been recent
      concerns raised by clinicians and researchers that this syndrome is overlooked in
      relation to second-generation or atypical antipsychotics. This review examines
      the recent literature relevant to second-generation antipsychotic (SGA)-induced
      akathisia. RECENT FINDINGS: Recent studies using large databases clearly indicate
      that extrapyramidal side effects, in particular akathisia, do occur with the
      SGAs, although the frequency is not as high as with the conventional
      antipsychotics. Risk factors include use of high doses, high potency SGAs, or
      combinations of SGAs with other psychotropic drugs, bipolar depression,
      palliative care settings, and comorbid substance abuse in psychosis. The dopamine
      hypothesis remains plausible for understanding the pathophysiology of akathisia.
      There is emerging evidence that mirtazapine may be useful in the treatment of
      acute akathisia. SUMMARY: Even though akathisia is less prevalent with SGAs than
      with the first-generation drugs, it remains clinically important and all
      clinicians should be conversant with its recognition and management.

PMID- 19378383
TI  - Impaired hippocampus-dependent and -independent learning in IL-6 deficient mice.
AB  - Interleukin-6 (IL-6) is a cytokine that, in addition to its essential role in the
      function of the immune system, is present in the central nervous system (CNS). In
      particular, pathologically increased CNS IL-6 has been linked to impairments in
      memory performance. Thus, the aim of our present study was to investigate
      hippocampus-dependent and -independent memory, in combination with exploratory
      and anxiety related behaviour in IL-6 knock-out (IL-6KO) mice. The experiments
      were performed with 9 male IL-6KO and 9 age matched male wild-type (CTRL) mice.
      Hippocampus-dependent learning was assessed with the Morris water maze (MWM),
      hippocampus-independent learning with the novel object recognition memory test
      (NORM). The test-battery for additional behavioural assessments included open
      field (OF), elevated plus maze (EPM) and forced swim test (FST). IL-6KO mice
      showed impaired memory processes in the NORM as well in the MWM test. This could
      not be explained by reduced general activity or increased baseline anxiety. But,
      there was evidence for a higher susceptibility for stress and reduced exploratory
      behaviour in IL-6KO mice. In conclusion, absent CNS IL-6 does not lead to an
      improvement in memory function, but instead to an impairment. As "too little and
      too much spoils everything", our findings do not contradict the hypothesis of an
      involvement of IL-6 in memory processes. However, it remains unclear if
      impairments of memory are a specific result of disturbed IL-6 signalling, or
      rather an epiphenomenon associated with reduced exploratory behaviour and stress
      resistance.

PMID- 19378384
TI  - High precision liquid chromatography analysis of dopaminergic and serotoninergic
      responses to acute alcohol exposure in zebrafish.
AB  - Zebrafish is gaining popularity in behavioral neuroscience in general and in
      alcohol research in particular. Alcohol is known to affect numerous molecular
      mechanisms depending on dose and administration regimen. Prominent among these
      mechanisms are several neurotransmitter systems. Here we analyze the responses of
      the dopaminergic and serotoninergic neurotransmitter systems of zebrafish to
      acute alcohol treatment (1 h long exposure of adult fish to 0.00%, 0.25%, 0.50%,
      or 1.00% ethyl alcohol) by testing the concentration of dopamine, its metabolite
      DOPAC, and serotonin and its metabolite 5-HIAA from whole brain extracts. We
      utilize a sensitive HPLC method and describe significant alcohol induced changes
      in zebrafish for the first time. We show that dopamine significantly increased in
      a quasi-linear dose dependent manner, DOPAC showed a smaller apparent increase
      which was non-significant, while both serotonin and 5-HIAA showed a significant
      increase only in the highest acute dose group. We discuss the methodological
      novelty of our work and theorize about the implications of the neurotransmitter
      level changes from a behavioral perspective.

PMID- 19378385
TI  - Evidence of multistability in a realistic computer simulation of hippocampus
      subfield CA1.
AB  - The manner in which hippocampus processes neural signals is thought to be central
      to the memory encoding process. A theoretically oriented literature has suggested
      that this is carried out via "attractors" or distinctive spatio-temporal patterns
      of activity. However, these ideas have not been thoroughly investigated using
      computational models featuring both realistic single-cell physiology and detailed
      cell-to-cell connectivity. Here we present a 452 cell simulation based on Traub
      et al.'s pyramidal cell [Traub RD, Jefferys JG, Miles R, Whittington MA, Toth K.
      A branching dendritic model of a rodent CA3 pyramidal neurone. J Physiol (Lond)
      1994;481:79-95] and interneuron [Traub RD, Miles R, Pyramidal cell-to-inhibitory
      cell spike transduction explicable by active dendritic conductances in inhibitory
      cell. J Comput Neurosci 1995;2:291-8] models, incorporating patterns of synaptic
      connectivity based on an extensive review of the neuroanatomic literature. When
      stimulated with a one second physiologically realistic input, our simulated
      tissue shows the ability to hold activity on-line for several seconds;
      furthermore, its spiking activity, as measured by frequency and interspike
      interval (ISI) distributions, resembles that of in vivo hippocampus. An
      interesting emergent property of the system is its tendency to transition from
      stable state to stable state, a behavior consistent with recent experimental
      findings [Sasaki T, Matsuki N, Ikegaya Y. Metastability of active CA3 networks. J
      Neurosci 2007;27:517-28]. Inspection of spike trains and simulated blockade of
      K(AHP) channels suggest that this is mediated by spike frequency adaptation. This
      finding, in conjunction with studies showing that apamin, a K(AHP) channel
      blocker, enhances the memory consolidation process in laboratory animals,
      suggests the formation of stable attractor states is central to the process by
      which memories are encoded. Ways that this methodology could shed light on the
      etiology of mental illness, such as schizophrenia, are discussed.

PMID- 19378388
TI  - John Maddox 1925-2009.

PMID- 19378387
TI  - Comparison of the effects of the synthetic pyrethroid Metofluthrin and
      phenobarbital on CYP2B form induction and replicative DNA synthesis in cultured
      rat and human hepatocytes.
AB  - High doses of Metofluthrin (MTF) have been shown to produce liver tumours in rats
      by a mode of action (MOA) involving activation of the constitutive androstane
      receptor leading to liver hypertrophy, induction of cytochrome P450 (CYP) forms
      and increased cell proliferation. The aim of this study was to compare the
      effects of MTF with those of the known rodent liver tumour promoter phenobarbital
      (PB) on the induction CYP2B forms and replicative DNA synthesis in cultured rat
      and human hepatocytes. Treatment with 50 microM MTF and 50 microM PB for 72 h
      increased CYP2B1 mRNA levels in male Wistar rat hepatocytes and CYP2B6 mRNA
      levels in human hepatocytes. Replicative DNA synthesis was determined by
      incorporation of 5-bromo-2'-deoxyuridine over the last 24 h of a 48 h treatment
      period. Treatment with 10-1000 microM MTF and 100-500 microM PB resulted in
      significant increases in replicative DNA synthesis in rat hepatocytes. While
      replicative DNA synthesis was increased in human hepatocytes treated with 5-50
      ng/ml epidermal growth factor or 5-100 ng/ml hepatocyte growth factor, treatment
      with MTF and PB had no effect. These results demonstrate that while both MTF and
      PB induce CYP2B forms in both species, MTF and PB only induced replicative DNA
      synthesis in rat and not in human hepatocytes. These results provide further
      evidence that the MOA for MTF-induced rat liver tumour formation is similar to
      that of PB and some other non-genotoxic CYP2B form inducers and that the key
      event of increased cell proliferation would not occur in human liver.

PMID- 19378389
TI  - Author's reply to: Vandijck et al. Enterobacteriaceae bacteremia after liver
      transplantation.

PMID- 19378390
TI  - The clinical utility of biomarkers and the nonalcoholic  steatohepatitis CRN
      liver biopsy scoring system in patients  with nonalcoholic fatty liver disease.
AB  - BACKGROUND AND AIMS: We identified patients with nonalcoholic fatty liver disease
      (NAFLD) to determine the predictive value of serum markers to diagnose
      histological steatohepatitis (NASH). METHODS: Demographic, serological,
      radiological and histological variables on 95 consecutive patients with NAFLD
      were recorded. The serum markers studied were CK18, Hyaluronic acid, TIMP 1 and
      YKL 40. The NAS score and the metavir score were the histological scoring systems
      used. RESULTS: CK18 levels were higher in the NASH group compared to the simple
      steatosis group (394 +/- 53 micro/L vs 194 +/- 26 micro/L; P < 0.05). In
      assessing clinical effectiveness, CK18 yielded an AUC of 0.8 for NASH (cut-off
      value 300 micro/L gives PPV 81% and NPV 85%).The fibrosis markers showed no
      differences between groups. We stratified the same cohort according to liver
      fibrosis (F0 vs F1-F4). Fibrosis was associated with advanced age, high body mass
      index and type 2 diabetes. The biomarkers performed relatively poorly at
      identifying liver fibrosis (F1-F4), with HA performing the best (AUC 0.73);
      performance improved for advanced fibrosis (F3/F4) - (HA: AUC 0.77). The NAS
      score performed the best overall at identifying liver fibrosis (AUC 0.79).
      DISCUSSION: CK18 is the only biomarker studied that can identify NASH.
      Additionally, liver biopsy should be performed in all high risk patients to
      determine the standardised NAS score to identify patients at high risk of disease
      progression.

PMID- 19378391
TI  - Trends of ulcerative colitis-associated colorectal cancer in  Korea: A KASID
      study.
AB  - BACKGROUND AND AIM: The number of patients with ulcerative colitis (UC) in Korea
      has increased. In addition, the number of patients with colorectal cancer (CRC)
      associated with UC has also increased. Therefore, this population-based
      nationwide study was conducted to investigate the incidence of CRC in patients
      with UC in Korea and compare these results to those of studies conducted in other
      countries. METHODS: The Korean Association for the Study of Intestinal Diseases
      (KASID) reviewed 7061 cases of UC that occurred between 1970 and 2005 and found a
      total of 26 cases of CRC. RESULTS: The overall prevalence of CRC in patients with
      UC was 0.37%. In addition, the estimated cumulative risk of UC-associated CRCs
      was 0.7% for patients that had UC for 10 years, 7.9% for patients that had UC for
      20 years, and 33.2% for patients that had UC for 30 years. The mean age at the
      time of diagnosis with CRC was 49.6 years, and the mean duration of UC prior to
      the development of CRC was 11.5 years. Most UC-associated CRCs were diagnosed
      after they were already in advanced stages; however, the stage at diagnosis was
      lower in patients that had good compliance with medical treatment. CONCLUSION:
      The cumulative incidence of UC-associated CRCs in Korea was found to be
      comparable to that of western countries. The overall occurrence of UC-associated
      CRC in Korea may be growing, therefore, intensive surveillance colonoscopy and
      constructive chemoprevention should be encouraged to enable early detection and
      treatment of UC-associated CRCs in Korea.

PMID- 19378392
TI  - Opening Pandora's box: comparative studies of genetic mating systems reveal
      reproductive complexity.
AB  - Genetic analyses of realized reproductive success have fundamentally changed our
      understanding of mating behaviour in natural systems. While behavioural
      ecologists have long been interested in what factors influence mating behaviour,
      early studies were limited to direct observations of matings and thus provided an
      incomplete picture of reproductive activity. Genetic assessments of parentage
      have revolutionized the study of reproductive behaviour, revealing that many
      individuals engage in extra-pair copulations (Griffith et al. 2002) and that
      social mating partners frequently invest substantial resources into raising
      offspring that are unrelated to one or both of them (Avise et al. 2002). While
      these findings have changed the way we think about reproductive behaviour, most
      investigations of genetic parentage have been restricted to single populations at
      a single point in time, obscuring spatial and/or temporal variation in mating
      behaviour and limiting our ability to determine how environmental changes can
      lead to shifts in mating strategies. In this issue of Molecular Ecology, Mobley &
      Jones (2009) compare genetic mating behaviour across five populations of
      Syngnathus floridae (Fig. 1), a widespread species of pipefish distributed along
      the Gulf- and Atlantic Coasts of North America. The authors document how genetic
      mating behaviour varies across space in S. floridae and identify correlations
      between reproductive variation and particular ecological characteristics. Mobley
      & Jones' paper is one of an increasing number of studies which address the
      question of how ecological variables influence mating behaviour, and highlights
      how our understanding of mating system variation and evolution is likely to
      expand through the wider application of high-throughput parentage assessment in a
      comparative context.

PMID- 19378393
TI  - From 4S to IDEAL: the health economics of the statin trials.
AB  - The introduction of statins led to much interest in their health economic aspects
      as they were initially perceived as efficacious but potentially expensive.
      Consequently, abundant literature exists examining the cost effectiveness of
      various statins, with analyses estimating the costs of preventing a single
      cardiovascular event using trial-based data, as well as long-term modelling
      studies using standardized outcomes such as cost per life-years gained or cost
      per quality-adjusted life-years. Economic evaluations based on clinical trials
      with hard endpoints indicate that the improved care associated with statin
      therapy came at a reasonable price in most risk groups. Variations between study
      results can largely be explained by differences in drug prices and absolute risk
      in the studied populations. This holds true for both within-trial analyses and
      modelling studies. The introduction of generic statins has led to sharp price
      reductions. Consequently, statin use today would be associated with greater cost
      savings in the indications that were first studied in clinical trials. New
      therapies entering the field must now compare favourably with statin therapy,
      whereas earlier a comparison versus placebo would have been sufficient to
      demonstrate cost effectiveness.

PMID- 19378394
TI  - Six-minute walking test after cardiac surgery: instructions  for an appropriate
      use.
AB  - The 6-min walking test is a practical, simple, inexpensive test, which does not
      require any exercise equipment or advanced training. The test has been proposed
      both as a functional status indicator and as an outcome measure in various
      categories of patients (postmyocardial infarction, heart failure, postcardiac
      surgery) admitted to rehabilitation programs. The purpose of this study is to
      review the literature regarding the usefulness of 6-min walking test for the
      evaluation of patients entering a cardiac rehabilitation program early after
      cardiac/thoracic surgery. The test is feasible and safe, even in elderly and
      frail patients, shortly after admission to an in-hospital rehabilitation program.
      The results of the test is influenced by many demographic and psychological
      variables, such as age, sex (with women showing lower functional capacity),
      comorbidity (particularly diabetes mellitus, arthritis, and other musculoskeletal
      diseases), disability, self-reported physical functioning, and general health
      perceptions; contrasting data correlate walked distance with left ventricular
      ejection fraction. Practical suggestions for test execution and results
      interpretation in this specific clinical setting are given according to current
      evidence.

PMID- 19378395
TI  - Prevalence of children with blood pressure measurements  exceeding adult cutoffs
      for optimal blood pressure  in Germany.
AB  - BACKGROUND: Despite a growing interest in the epidemiology of paediatric
      hypertension, data on how often blood pressure in children and adolescents
      already exceeds adult thresholds for optimal blood pressure are scarce. The aim
      of this study was to estimate the prevalence of higher-than-optimal and
      hypertensive blood pressure values according to adult cutoffs in an unselected
      representative sample of children and adolescents living in Germany. METHODS:
      Standardized oscillometric blood pressure measurements were performed in 14 730
      children aged 3-17 years (7203 girls and 7527 boys) participating in a nationally
      representative examination survey of children and adolescents living in Germany
      (The German Health Interview and Examination Survey for Children and Adolescents,
      KiGGS, response rate 67%). The mean of two measurements was used for this
      analysis. RESULTS: The prevalences of higher-than-optimal blood pressure values
      by adult criteria (>or=120/80 mmHg) increased with age and was 52.2% in boys aged
      14-17 years and 26.2% in girls aged 14-17 years (including 6.0% of boys and 1.4%
      of girls with hypertensive values >or=140/90 mmHg). More than half of these
      adolescents with nonoptimal blood pressure values had additional cardiovascular
      risk factors (overweight defined as body mass index >or=90th percentile for sex
      and age, dyslipidaemia defined as total cholesterol >5.0 mmol/l or high-density
      lipoprotein cholesterol less than 1.0 mmol/l or smoking). CONCLUSION: These
      results suggest the need for routine blood pressure measurements in children and
      adolescents as required by clinical guidelines, for more attention to coexisting
      other cardiovascular risk factors and for a sustained focus on healthy lifestyles
      that can be learned best at a young age.

PMID- 19378396
TI  - Parent's conceptions of intensive group training. The case of cerebral palsy.
AB  - PURPOSE: The aim was to explore what wants and needs intensive group training
      (IGT) fulfil for parents of children with cerebral palsy (CP) and what problems
      that may arise due to participation. METHODS: A phenomenograpical approach was
      used. Semi-structured interviews were conducted to elicit information about what
      participation means to parents. RESULTS: Five overarching categories expressing
      positive functions of IGT were identified: IGT as knowledge promotion, as a
      complementary training resource, as a bracket to ordinary life, as a means to
      promote relations with therapists, and as a leisure-activity. One category: IGT
      as risk for ill-being expresses perceived problems. Each category is in turn
      divided into a number of subconceptions - 13 conceptions of this kind were
      identified. CONCLUSIONS: The conceptions express positive and negative functions
      of IGT as perceived by parents. These functions in turn can be considered as
      reflections of basic wants and needs. The results demonstrate that IGT have a
      potential to contribute to feelings of enhanced care competence among parents, of
      being supported and of increased strength and vitality. All parents did not have
      needs of participation in IGT for themselves. There is also a risk that IGT is
      experienced as an additional burden and may have negative effects on family
      functioning.

PMID- 19378397
TI  - Interaction of antitumor platinum complexes with human liver  microsomal
      cytochromes P450.
AB  - Interaction of nine human hepatic cytochromes P450 (CYP1A2, CYP2A6, CYP2B6,
      CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) with six platinum complexes
      was studied using pooled human microsomes. The compounds used were cisplatin,
      oxaliplatin, carboplatin, transplatin, and trans-[PtCl2(NH3) (Am)], where Am=2
      methylbutylamine or sec-butylamine. No significant inhibition of all CYP
      activities by carboplatin was observed. With cisplatin and oxaliplatin, a minor
      inhibition of CYP2C9 enzyme (75% of control at 400 miromol/l of these complexes)
      was seen; cisplatin also inhibited slightly the CYP2B6 activity (85% of control).
      With respect to plasma levels of cisplatin obtained in clinical applications,
      these effects are probably not important. In contrast, clinically ineffective
      transplatin, inhibited the CYP2B6 as well as CYP2C9 activities significantly (to
      50-35% of control at 100 micromol/l); also, an inhibition of CYP2E1 activity was
      found here (to 70% at 100 micromol/l). Two other derivatives of transplatin (new
      antitumor agents with trans geometry), inhibited CYP activities more strongly
      reaching nearly a complete inhibition of the respective CYP activities at
      concentration of 200 micromol/l. Half maximal inhibitory concentration values
      were found in the range of tens of micromol/l indicating that there is a
      possibility of potential interactions of these compounds with drugs metabolized
      by CYP3A4, CYP2E1, CYP2D6, CYP2C19, CYP2B6, CYP2A6, and CYP1A2. Interestingly,
      clinically non-significant inhibition was found with the CYP2C9 and CYP2C8
      indicating low probability of interactions with, for example, warfarin. The
      results document that the new antitumor agents based on the transplatin should be
      more thoroughly tested for interactions with liver microsomal drug-metabolizing
      cytochromes P450.

PMID- 19378398
TI  - Hitching a lift on the road to speciation.
AB  - Understanding how speciation can take place in the presence of homogenizing gene
      flow remains a major challenge in evolutionary biology. In the early stages of
      ecological speciation, reproductive isolation between populations occupying
      different habitats is expected to be concentrated around genes for local
      adaptation. These genomic regions will show high divergence while gene exchange
      in other regions of the genome should continue relatively unimpaired, resulting
      in low levels of differentiation. The problem is to explain how speciation
      progresses from this point towards complete reproductive isolation, allowing
      genome-wide divergence. A new study by Via and West (2008) on speciation between
      host races of the pea aphid, Acyrthosiphon pisum, introduces the mechanism of
      'divergence hitchhiking' which can generate large 'islands of differentiation'
      and facilitate the build-up of linkage disequilibrium, favouring increased
      reproductive isolation. This idea potentially removes a major stumbling block to
      speciation under continuous gene flow.

PMID- 19378399
TI  - Homoploid hybrid speciation in animals.
AB  - Among animals, evidence for homoploid hybrid speciation (HHS, i.e. the creation
      of a hybrid lineage without a change in chromosome number) was limited until
      recently to the virgin chub, Gila seminuda, and some controversial data in
      support of hybrid status for the red wolf, Canis rufus. This scarcity of
      evidence, together with pessimistic attitudes among zoologists about the
      evolutionary importance of hybridisation, prompted the view that HHS is extremely
      rare among animals, especially as compared with plants. However, in recent years,
      the literature on animal HHS has expanded to include several new putative
      examples in butterflies, ants, flies and fishes. We argue that this evidence
      suggests that HHS is far more common than previously thought and use it to
      provide insights into some of the genetic and ecological aspects associated with
      this type of speciation among animals.

PMID- 19378400
TI  - Evidence for multiple introductions of Centaurea stoebe micranthos (spotted
      knapweed, asteraceae) to North America.
AB  - Invasive species' success may depend strongly on the genetic resources they
      maintain through the invasion process. We ask how many introductions have
      occurred in the North American weed Centaurea stoebe micranthos (Asteraceae), and
      explore whether genetic diversity and population structure have changed as a
      result of introduction. We surveyed individuals from 15 European native range
      sites and 11 North American introduced range sites at six polymorphic
      microsatellite loci. No significant difference existed in the total number of
      alleles or in the number of private alleles found in each range. Shannon-Weaver
      diversity of phenotype frequencies was also not significantly different between
      the ranges, while expected heterozygosity was significantly higher in the
      invasive range. Population structure was similar between the native range and the
      invasive range, and isolation by distance was not significant in either range.
      Traditional assignment methods did not allocate any North American individuals to
      the sampled European populations, while Bayesian assignment methods grouped
      individuals into nine genetic clusters, with three of them shared between North
      America and Europe. Invasive individuals tended to have genetically admixed
      profiles, while natives tended to assign more strongly to a single cluster. Many
      North American individuals share assignment with Romania and Bulgaria, suggesting
      two separate invasions that have undergone gene flow in North America. Samples
      from three other invasive range sites were genetically distinct, possibly
      representing three other unique introductions. Multiple introductions and the
      maintenance of high genetic diversity through the introduction process may be
      partially responsible for the invasive success of C. stoebe micranthos.

PMID- 19378401
TI  - Contrasting demographic and genetic estimates of dispersal in the endangered
      Coahuilan box turtle: a contemporary approach to conservation.
AB  - The evolutionary viability of an endangered species depends upon gene flow among
      subpopulations and the degree of habitat patch connectivity. Contrasting
      population connectivity over ecological and evolutionary timescales may provide
      novel insight into what maintains genetic diversity within threatened species. We
      employed this integrative approach to evaluating dispersal in the critically
      endangered Coahuilan box turtle (Terrapene coahuila) that inhabits isolated
      wetlands in the desert-spring ecosystem of Cuatro Cienegas, Mexico. Recent
      wetland habitat loss has altered the spatial distribution and connectivity of
      habitat patches; and we therefore predicted that T. coahuila would exhibit
      limited movement relative to estimates of historic gene flow. To evaluate
      contemporary dispersal patterns, we employed mark-recapture techniques at both
      local (wetland complex) and regional (intercomplex) spatial scales. Gene flow
      estimates were obtained by surveying genetic variation at nine microsatellite
      loci in seven subpopulations located across the species' geographical range. The
      mark-recapture results at the local spatial scale reveal frequent movement among
      wetlands that was unaffected by interwetland distance. At the regional spatial
      scale, dispersal events were relatively less frequent between wetland complexes.
      The complementary analysis of population genetic substructure indicates strong
      historic gene flow (global F(ST) = 0.01). However, a relationship of genetic
      isolation by distance across the geographical range suggests that dispersal
      limitation exists at the regional scale. Our approach of contrasting direct and
      indirect estimates of dispersal at multiple spatial scales in T. coahuila conveys
      a sustainable evolutionary trajectory of the species pending preservation of
      threatened wetland habitats and a range-wide network of corridors.

PMID- 19378402
TI  - Range-wide genetic homogeneity in the California sea mussel (Mytilus
      californianus): a comparison of allozymes, nuclear DNA markers, and mitochondrial
      DNA sequences.
AB  - We tested for genetic differentiation among six populations of California sea
      mussels (Mytilus californianus) sampled across 4000 km of its geographical range
      by comparing patterns of variation at four independent types of genetic markers:
      allozymes, single-copy nuclear DNA markers, and DNA sequences from the male and
      female mitochondrial genomes. Despite our extensive sampling and genotyping
      efforts, we detected no significant differences among localities and no signal of
      isolation by distance suggesting that M. californianus is genetically homogeneous
      throughout its range. This concordance differs from similar studies on other
      mytilids, especially in the role of postsettlement selection generating
      differences between exposed coastal and estuarine habitats. To assess if this
      homogeneity was due to M. californianus not inhabiting estuarine environments, we
      reviewed studies comparing allozymes with other classes of nuclear DNA markers.
      Although both types of markers gave broadly consistent results, there was a bias
      favouring studies in which allozymes were more divergent than DNA markers (nine
      to three) and a disproportionate number of these cases involved marine taxa
      (seven). Furthermore, allozymes were significantly more heterogeneous than DNA
      markers in three of the four studies that sampled coastal and estuarine habitats.
      We conclude that the genetic uniformity exhibited by M. californianus may result
      from a combination of extensive gene flow and the lack of exposure to strong
      selective gradients across its range.

PMID- 19378403
TI  - High connectivity on a global scale in the pelagic wahoo, Acanthocybium solandri
      (tuna family Scombridae).
AB  - The population genetic structure and phylogeography of wahoo, Acanthocybium
      solandri, were investigated on a global scale with intron six of lactate
      dehydrogenase-A (ldhA6, 8 locations, N = 213) and mtDNA cytochrome b (Cytb, 10
      locations, N = 322). Results show extensive sharing of haplotypes across the
      wahoo's entire global range, and analyses were unable to detect significant
      structure (nuclear F(ST) = 0.0125, P = 0.106; mtDNA Phi(ST) < 0.0001, P = 0.634).
      Power analyses indicated 95% confidence in detecting nuclear F(ST) > or = 0.0389
      and mtDNA Phi(ST) > or = 0.0148. These findings appear unique, as most other
      tunas, billfishes, and oceanic sharks exhibit significant population structure on
      the scale of East-West Atlantic, Atlantic vs. Indian-Pacific, or East-West
      Pacific. Overall nuclear heterozygosity (H = 0.714) and mtDNA haplotype diversity
      (h = 0.918) are both high in wahoo, while overall mtDNA nucleotide diversity (pi
      = 0.006) and nuclear nucleotide diversity (pi = 0.004) are uniformly low,
      indicating a recent increase in population size. Coalescence analyses yield an
      estimate of effective female population size (NeF) at approximately 816,000, and
      a population bottleneck approximately 690,000 years ago. However, conclusions
      about population history from our Cytb data set are not concordant with a control
      region survey, a finding that will require further investigation. This is the
      first example of a vertebrate with a single globally distributed population, a
      finding we attribute to extensive dispersal at all life stages. The indications
      of a worldwide stock for wahoo reinforce the mandate for international
      cooperation on fisheries issues.

PMID- 19378404
TI  - Historical divergence vs. contemporary gene flow: evolutionary history of the
      calcicole Ranunculus alpestris group (Ranunculaceae) in the European Alps and the
      Carpathians.
AB  - Although many species have similar total distributional ranges, they might be
      restricted to very different habitats and might have different phylogeographical
      histories. In the European Alps, our excellent knowledge of the evolutionary
      history of silicate-dwelling (silicicole) plants is contrasted by a virtual lack
      of data from limestone-dwelling (calcicole) plants. These two categories exhibit
      fundamentally different distribution patterns within the Alps and are expected to
      differ strongly with respect to their glacial history. The calcicole Ranunculus
      alpestris group comprises three diploid species of alpine habitats. Ranunculus
      alpestris s. str. is distributed over the southern European mountain system,
      while R. bilobus and R. traunfellneri are southern Alpine narrow endemics. To
      explore their phylogenetic relationships and phylogeographical history, we
      investigated the correlation between information given by nuclear and chloroplast
      DNA data. Analyses of amplified fragment length polymorphism fingerprints and
      matK sequences gave incongruent results, indicative for reticulate evolution. Our
      data highlight historical episodes of range fragmentation and expansion,
      occasional long-distance dispersal and on-going gene flow as important processes
      shaping the genetic structure of the group. Genetic divergence, expressed as a
      rarity index ('frequency-down-weighted marker values') seems a better indicator
      of historical processes than patterns of genetic diversity, which rather mirror
      contemporary processes as connectivity of populations and population sizes. Three
      phylogeographical subgroups have been found within the R. alpestris group,
      neither following taxonomy nor geography. Genetic heterogeneity in the Southern
      Alps contrasts with Northern Alpine uniformity. The Carpathians have been
      stepwise-colonised from the Eastern Alpine lineage, resulting in a marked
      diversity loss in the Southern Carpathians. The main divergence within the group,
      separating the ancestor of the two endemic species from R. alpestris s. str.,
      predates the Quaternary. Therefore, range shifts produced by palaeoclimatic
      oscillations seem to have acted on the genetic structure of R. alpestris group on
      a more regional level, e.g. triggering an allopatric separation of R.
      traunfellneri from R. bilobus.

PMID- 19378405
TI  - Phylogeography of Pinus tabulaeformis Carr. (Pinaceae), a dominant species of
      coniferous forest in northern China.
AB  - How coniferous trees in northern China changed their distribution ranges in
      response to Quaternary climatic oscillations remains largely unknown. Here we
      report a study of the phylogeography of Pinus tabulaeformis, an endemic and
      dominant species of coniferous forest in northern China. We examined sequence
      variation of maternally inherited, seed-dispersed mitochondrial DNA (mtDNA) (nad5
      intron 1 and nad4/3-4) and paternally inherited, pollen- and seed-dispersed
      chloroplast DNA (cpDNA) (rpl16 and trnS-trnG) within and among 30 natural
      populations across the entire range of the species. Six mitotypes and five
      chlorotypes were recovered among 291 trees surveyed. Population divergence was
      high for mtDNA variation (G(ST) = 0.738, N(ST) = 0.771) indicating low levels of
      seed-based gene flow and significant phylogeographical structure (N(ST) > G(ST),
      P < 0.05). The spatial distribution of mitotypes suggests that five distinct
      population groups exist in the species: one in the west comprising seven
      populations, a second with a north-central distribution comprising 15
      populations, a third with a southern and easterly distribution comprising five
      populations, a fourth comprising one central and one western population, and a
      fifth comprising a single population located in the north-central part of the
      species' range. Each group apart from the fourth group is characterized by a
      distinct mitotype, with other mitotypes, if present, occurring at low frequency.
      It is suggested, therefore, that most members of each group apart from Group 4
      are derived from ancestors that occupied different isolated refugia in a previous
      period of range fragmentation of the species, possibly at the time of the Last
      Glacial Maximum. Possible locations for these refugia are suggested. A comparison
      of mitotype diversity between northern and southern subgroups within the north
      central group of populations (Group 2) showed much greater uniformity in the
      northern part of the range both within and between populations. This could
      indicate a northward migration of the species from a southern refugium in this
      region during the postglacial period, although alternative explanations cannot be
      ruled out. Two chlorotypes were distributed across the geographical range of the
      species, resulting in lower levels of among-population chlorotype variation. The
      geographical pattern of variation for all five chlorotypes provided some
      indication of the species surviving past glaciations in more than one refugium,
      although differentiation was much less marked, presumably due to the greater
      dispersal of cpDNA via pollen.

PMID- 19378406
TI  - Host-driven divergence in the parasitic plant Orobanche minor Sm.
      (Orobanchaceae).
AB  - Many parasitic angiosperms have a broad host range and are therefore considered
      to be host generalists. Orobanche minor is a nonphotosynthetic root parasite that
      attacks a range of hosts from taxonomically disparate families. In the present
      study, we show that O. minor sensu lato may comprise distinct, genetically
      divergent races isolated by the different ecologies of their hosts. Using a three
      pronged approach, we tested the hypothesis that intraspecific taxa O. minor var.
      minor and O. minor ssp. maritima parasitizing either clover (Trifolium pratense)
      or sea carrot (Daucus carota ssp.gummifer), respectively, are in allopatric
      isolation. Morphometric analysis revealed evidence of divergence but this was
      insufficient to define discrete, host-specific taxa. Intersimple sequence repeat
      (ISSR) marker-based data provided stronger evidence of divergence, suggesting
      that populations were isolated from gene flow. Phylogenetic analysis, using
      sequence-characterized amplified region (SCAR) markers derived from ISSR loci,
      provided strong evidence for divergence by clearly differentiating sea carrot
      specific clades and mixed-host clades. Low levels of intrapopulation SCAR marker
      sequence variation and floral morphology suggest that populations on different
      hosts are probably selfing and inbreeding. Morphologically cryptic Orobanche taxa
      may therefore be isolated from gene flow by host ecology. Together, these data
      suggest that host specificity may be an important driver of allopatric speciation
      in parasitic plants.

PMID- 19378407
TI  - Social constraint and an absence of sex-biased dispersal drive fine-scale genetic
      structure in white-winged choughs.
AB  - This study used eight polymorphic microsatellite loci to examine the relative
      effects of social organization and dispersal on fine-scale genetic structure in
      an obligately cooperative breeding bird, the white-winged chough (Corcorax
      melanorhamphos). Using both individual-level and population-level analyses, it
      was found that the majority of chough groups consisted of close relatives and
      there was significant differentiation among groups (F(ST) = 0.124). However,
      spatial autocorrelation analysis revealed strong spatial genetic structure among
      groups up to 2 km apart, indicating above average relatedness among neighbours.
      Multiple analyses showed a unique lack of sex-biased dispersal. As such, choughs
      may offer a model species for the study of the evolution of sex-biased dispersal
      in cooperatively breeding birds. These findings suggest that genetic structure in
      white-winged choughs reflects the interplay between social barriers to dispersal
      resulting in large family groups that can remain stable over long periods of
      times, and short dispersal distances which lead to above average relatedness
      among neighbouring groups.

PMID- 19378408
TI  - Group composition affects male reproductive partitioning in a cooperatively
      breeding cichlid.
AB  - Individuals within groups of cooperatively breeding species may partition
      reproduction, with the dominant pair often taking the largest share. The
      dominant's ability to reproductively control subordinates may depend on
      differences in competitive ability, due to, e.g. body size differences, but may
      also depend on the number of same-sex competitors inside the group. We tested
      experimentally whether subordinates reproduce more when these subordinates are
      large or when a second subordinate of the same sex need to be controlled by the
      dominants, using the cooperatively breeding cichlid Neolamprologus pulcher.
      Dominant pairs were assisted by a large and a small unrelated subordinate; sexes
      of these fish were varied in a full-factorial design (giving four treatments).
      Dominant males lost significantly more parentage to the large subordinate male
      when a small subordinate male was also present, compared to when a small
      subordinate female was present. However, subordinate paternity was generally low
      and did not significantly curb total dominant male reproductive output, which was
      more affected by the sizes and numbers of reproductive females present inside his
      group. Dominant female maternity, clutch sizes and total output did not depend on
      the treatments. Subordinate-subordinate reproduction was virtually absent (one
      out of 874 offspring). Female subordinates were more likely to provide care for
      their own broods. In contrast, male subordinates did not adjust their level of
      care to their parentage. Variability in female subordinate alloparental brood
      care was particularly high, with females showing more care than males in general.
      We also detected effects of growth rate and food ration on parentage independent
      of the treatments, most notably: (i) a trade-off between dominant male growth
      rate and paternity; (ii) a decrease in dominant male paternity with increasing
      food ration; (iii) a positive effect of growth rate on paternity in small males.
      We conclude that dominant males should be sensitive to the number and sizes of
      subordinate males present in their group, particularly when these subordinates
      are not helpful or grow fast, and food is plentiful. Dominant females should be
      less sensitive, because female subordinates do not appear to impose reproductive
      costs and can be helpful through alloparental brood care.

PMID- 19378409
TI  - Microbial communities and interactions in the lone star tick, Amblyomma
      americanum.
AB  - To quantify microbial composition and interactions, we identified prokaryotic
      communities in the lone star tick (Amblyomma americanum) based on 16S rRNA gene
      sequences and direct probing. The lone star tick is the vector of emerging
      diseases and host to additional symbionts of unknown activity, and is
      representative of other blood-sucking arthropods. We evaluated the potential for
      vertical (transovarial) transmission by molecular analysis of microbial symbionts
      from egg and larval clutches. Direct probing of adults (N = 8 populations from
      the southeastern and midwestern USA, 900 ticks total) revealed three vertically
      transmitted symbionts: a Coxiella symbiont occurred at 100% frequency, Rickettsia
      species occurred in 45-61% of all ticks in every population and an Arsenophonus
      symbiont occurred in 0-90% of ticks per population. Arsenophonus and Rickettsia
      exhibited significant heterogeneity in frequency among populations. The human
      pathogens Ehrlichia chafeensis and Borrelia lonestari were rare in most
      populations. Additional microbes were detected sporadically. Most ticks (78%)
      were co-infected by two or three microbes but statistical analysis indicated no
      significant deviation from random co-occurrence. Our findings indicate that
      microbial communities within lone star ticks are diverse, and suggest that direct
      probing for a wider range of prokaryotes and application of quantitative
      polymerase chain reaction (PCR) may provide further insights into microbial
      interactions within disease vectors. Our results also emphasize the close
      phylogenetic relationship between tick symbionts and human pathogens, and
      consistent differences in their prevalence.

PMID- 19378410
TI  - Patterns and rates of nucleotide substitution, insertion and deletion in the
      endosymbiont of ants Blochmannia floridanus.
AB  - Genome reduction is a general process that has been studied in numerous symbiotic
      bacteria associated with insects. We investigated the last stages of genome
      degradation in Blochmannia floridanus, a mutualistic bacterial endosymbiont of
      the ant Camponotus floridanus. We determined the tempo (rates of insertion and
      deletion) and mode (size and number of insertion-deletion events) of the process
      in the last 200,000 years by analysing a total of 16 intergenic regions in
      several strains of this endosymbiont from different ant populations. We provide
      the first calculation of the reduction rate for noncoding DNA in this
      endosymbiont (2.2 x 10(-8) lost nucleotides/site/year) and compare it with the
      rate of loss in other species. Our results confirm, as it has been observed in
      other organisms like Buchnera aphidicola or Rickettsia spp., that deletions
      larger than one nucleotide can still appear in advanced stages of genome
      reduction and that a substitutional deletion bias exists. However, this bias is
      not due to a higher proportion of deletion over insertion events but to a few
      deletion events being larger than the rest. Moreover, we detected a
      substitutional AT bias that is probably responsible for the increase in the
      number of the small and moderate indel events in the last stages of genome
      reduction. Accordingly, we found intrapopulational polymorphisms for the detected
      microsatellites in contrast to the stability associated with these in free-living
      bacteria such as Escherichia coli.

PMID- 19378411
TI  - Integrating perception and action through cognitive neuropsychology (broadly
      conceived).

PMID- 19378412
TI  - Grasping visual illusions: consistent data and no dissociation.
AB  - The finding that the Ebbinghaus/Titchener illusion deceives perception but not
      grasping is usually seen as strong evidence for Goodale and Milner's (1992)
      notion of two parallel visual systems, one being conscious and deceived by the
      illusion (vision-for-perception) and the other being unconscious and not deceived
      (vision-for-action). However, this finding is controversial and led to studies
      with seemingly contradictory results. We argue that these results are not as
      contradictory as it might seem. Instead, studies consistently show similar
      effects of the illusion on grasping. The perceptual effects are strongly
      dependent on the specific perceptual measure employed. If, however, some
      methodological precautions are used, then these diverse perceptual results can be
      reconciled and point to a single internal size estimate that is used for
      perception and for grasping. This suggests that the Ebbinghaus illusion deceives
      a common representation of object size that is used by perception and action.

PMID- 19378413
TI  - Grasping Weber's illusion: the effect of receptor density differences on grasping
      and matching.
AB  - Weber found that distances between tactile stimuli on a high-receptor-density
      area are perceived as being larger than identical distances on a low-receptor
      density area (Weber's illusion). Previous studies of visual illusions suggest
      that illusion effects vary with the type of response given. Here we tested a
      modified version of Weber's illusion in which a solid object was placed on the
      forearm or hand. Blindfolded participants were required either to give a size
      estimation or to grasp the object. The results showed that size estimation of
      solid objects was consistent with Weber's illusion, whereas grasping responses
      showed an opposite pattern (e.g., larger hand opening for objects on the
      forearm). A second experiment showed that this pattern is not due to
      biomechanical differences induced by the difference in spatial position of the
      target objects on the hand and arm. We suggest that the larger grip aperture when
      grasping objects on the arm were due to an increase in safety margin as a
      response to greater uncertainty about the object dimensions due to reduced
      receptor density.

PMID- 19378414
TI  - Context influences on the preparation and execution of reaching movements.
AB  - The ability of rapidly adapting our motor behaviour in order to face the
      unpredictable changes in the surrounding environment is fundamental for survival.
      To achieve such a high level of efficiency our motor system has to assess
      continuously the context in which it acts, gathering all available information
      that can be relevant for planning goal-oriented movements. One still-debated
      aspect of movement organization is the nature and timing of motor planning. While
      motor plans are often taken to be concerned with the setting of kinematic
      parameters as a function of perceptual and motor factors, it has been suggested
      that higher level, cognitive factors may also affect planning. To explore this
      issue further, we asked 18 right-handed human participants to perform speeded
      hand-reaching movement toward a visual target in two different experimental
      settings, a reaction time (RT) paradigm (go-only task) and a countermanding
      paradigm. In both tasks participants executed the same movements, but in the
      countermanding task no-stop trials were randomly intermixed with stop trials. In
      stop trials participants were required to withhold the ongoing movement whenever
      a stop signal was shown. It is known that the presence of stop trials induces a
      consistent increase of the RTs of no-stop trials with respect to the RTs of go
      only trials. However, nothing is known about a similar effect for movement times
      (MTs). We found that RTs and MTs exhibit opposing tendencies, so that a decrease
      in the RT correspond to an increase in the MT and vice versa. This tendency was
      present in all our participants and significant in 90% of them. Furthermore we
      found a moderate, but again very consistent, anticorrelation between RTs and MTs
      on a trial-by-trial base. These findings are consistent with strategic changes in
      movement programmes for the very same movements under different cognitive
      contexts, requiring different degrees of feedback-driven control during movement.

PMID- 19378415
TI  - Threat perception and targeting: the brainstem-amygdala-cortex alarm system in
      action?
AB  - Optimizing our responses to physical threats is of clear adaptive value, yet
      influences of threat perception specific to visual guidance of action have
      received little attention. Here, we assess effects of threat perception on a
      targeting task, finding improved performance for peripheral targets relative to
      central targets. These effects of threat were absent either when the task did not
      involve targeting or when targeting followed high-arousal, positive-valence
      stimuli. Additionally, the effects of threat showed a nasal- versus temporal
      visual hemifield asymmetry and were absent when target stimuli isolated S-cone
      photoreceptor function. These findings suggest that the superior colliculus,
      which is activated following threat perception, shows clear visual-field
      asymmetry, receives no direct S-cone-based inputs from the retina, and forms part
      of a hypothesized direct brainstem-amygdala-cortex alarm system, mediates this
      effect.

PMID- 19378416
TI  - Action-dependent plasticity in peripersonal space representations.
AB  - The space immediately around the body is represented by multisensory integrative
      processes implemented in frontal and parietal lobes. This network has basically a
      motor function--that is, planning an approaching or defensive motor response to
      stimuli presented close to the body. Peripersonal space representations are
      highly plastic as a function of experience. Indeed, using a tool to act in far
      space can drive an elongation of peripersonal space representation towards the
      acting space. In this review functional and dynamic properties of such plasticity
      are reviewed in light of recent experimental findings from our own group and
      other laboratories.

PMID- 19378417
TI  - Reversal of streptozotocin-induced hyperglycemia by continuous supply of
      betacellulin in mice.
AB  - Previous studies have shown the efficacy of betacellulin (BTC) to promote beta
      cell regeneration. Because of its short half-life, however, the effect of BTC may
      have been underestimated. This study was conducted to assess the effect of
      continuous administration of BTC on beta-cell regeneration. Adenovirus vectors
      encoding proBTC (Ad-proBTC) and mature BTC (Ad-mBTC) were prepared, and the
      efficacy of secretion of BTC was compared in AML12 hepatocytes. When AML12 cells
      were infected with Ad-proBTC or Ad-mBTC, cells infected with Ad-mBTC secreted
      considerably larger amount of BTC. We then infused Ad-mBTC into the mouse tail
      vein. Expression of BTC was detected in the liver for at least 21 days, and serum
      BTC was maintained at approximately 1 ng/ml for 7 days. When Ad-mBTC was infused
      immediately after administration of STZ (170 mg/kg), elevation of the plasma
      glucose induced by STZ was markedly inhibited, and the plasma glucose
      concentration remained at less than 200 mg/dl for 21 days. The insulin content
      and the beta-cell mass were significantly increased in Ad-mBTC-infused mice.
      These results indicate that continuous administration of BTC is quite effective
      in promoting regeneration of beta-cells.

PMID- 19378418
TI  - MRNA expression of members of the IGF system in the organ of Corti, the modiolus
      and the stria vascularis of newborn rats.
AB  - We analyzed the mRNA expression of the insulin-like growth factor (IGF) family
      genes and of selected downstream pathway genes using the Affymetrix microarray
      system and confirmatory RT-PCR in the freshly prepared organ of Corti (OC),
      modiolus (MOD) and stria vascularis (SV) from neonatal rats (3-5 days old) and
      after 24h in culture. Among the seven members of the IGF family analyzed in this
      paper, IGF1, IGF2 and IGF-binding protein (IGFBP2) had the highest basal
      expression in all regions. Preparatory stress and culture increased the
      expression of IGF2, IGFBP2, IGFBP3, IGFBP5, glucose transporterl (GLUT1), signal
      transducer, and activator of transcription3 (STAT3), phosphoinositide-3-kinase
      regulatory subunit (Pik3r1), Jun oncogene (c-jun) and decreased that of mitogen
      activated protein kinases MAPK3 and MAPK14 in all regions. Region-specific
      changes were observed in OC (GLUT1), MOD (IGFBP3 and c-jun) and SV (IGF2 and
      IGFBP2).

PMID- 19378419
TI  - Signal transduction involved in CTGF-induced production of chemokines in
      mesangial cells.
AB  - OBJECTIVE AND DESIGN: This study investigates the regulatory role of connective
      tissue growth factor (CTGF) on production of fractalkine, monocyte
      chemoattractant protein-1 (MCP-1) and regulated on activation, normal T cell
      expressed and secreted (RANTES) in human mesangial cells, and explore the
      mechanisms of CTGF action. METHODS: Cultured human mesangial cells were treated
      with CTGF. Expressions of mRNA and proteins of fractalkine, MCP-1 and RANTES were
      analyzed by real-time polymerase chain reaction (PCR) and by enzyme-linked
      immunosorbent assay, respectively. Expressions of phosphorylated extracellular
      signal-regulated kinase 1/2 (ERK1/2), phosphoinositide 3-kinase (PI3-K) and
      protein kinase B (PKB) were assessed by Western blotting. Activities of nuclear
      factor-KB (NF-KB) were determined by NF-kappaB luciferase reporter assay.
      RESULTS: CTGF enhanced the mRNA expressions and protein release of fractalkine,
      MCP-1 and RANTES, and the expressions of phosphorylated ERK1/2, PI3-K and PKB,
      and activities of NF-KB. Blockade of ERK1/2 inhibited the CTGF-induced expression
      ofphosphorylated ERK1/2 and NF-kappaB, and partially decreased the expressions of
      the above chemokines. PI3-K blockade downregulated the CTGF-stimulated
      expressions of phosphorylated PI3-K, PKB and NF-kappaB but not phosphorylated
      ERK1/2, partially decreased the expressions of the above chemokines. NF-kappaB
      blockade abrogated the CTGF-activated NF-kappaB and partially decreased the
      expressions of the above chemokines. Soluble heparin and K252a, an inhibitor of
      Trk, blocked CTGF-induced production of the above chemokines and the activation
      of the above signaling proteins. CONCLUSION: These results demonstrated that CTGF
      induces production of fractalkine, MCP-1 and RANTES via ERK1/2 and PI3-K/PKB/NF
      kappaB-dependent signal pathway mediated by cell surface heparin sulfate
      proteoglycans and the tyrosine kinase receptor TrkA in human mesangial cells.

PMID- 19378420
TI  - Troponin I concentrations in heparinized plasma and serum differ when measured
      with the Advia Centaur TnI-Ultra assay.

PMID- 19378421
TI  - Lifestyles and oxidative stress in type 2 diabetic patients.

PMID- 19378422
TI  - Usefulness of long-distance inverse polymerase chain reaction for molecular
      detection of 14q32 translocation in a clinical setting.
AB  - All mature B-cell leukaemias and lymphomas have a clonal Ig gene recombination,
      and half of them have a reciprocal chromosomal translocation involving the 14q32
      locus. The 14q32 translocation partners are variable, such as BCL-2, BCL-1 and
      BCL-6, thus accounting for the difficulty in molecular detection by the current
      genomic polymerase chain reaction (PCR) method. To identify B-cell clones
      efficiently with an Ig gene rearrangement and reciprocal inter-chromosomal
      translocation, we verified the usefulness, in a practical laboratory setting, of
      our modified long-distance inverse (LDI) PCR method for detecting IgH gene
      rearrangements involving inter- and intra-chromosomal segments. The total run
      time of this LDI PCR method was 5.5 h. Using 24 samples of mature B-cell
      leukaemias and lymphomas, the modified LDI PCR gave clonally rearranged amplicons
      in 83 % (20/24) of cases. Direct sequencing results of the amplicons revealed
      inter-chromosomal translocations in 5 cases (25 %) and intra-chromosomal
      rearrangements in the remaining 15 cases (75 %). The partners of the inter
      chromosomal translocation consisted of the 11q13.3 segment containing a partial
      BCL1 sequence in 3 cases; 18q21.3 segment containing a partial BCL2 sequence in
      one case; and a segment of 7ql1.2 in one case. We present an LDI PCR-based
      methodology for the efficient identification of 14q32 translocations, with
      modifications to reduce the total run time to within one day.

PMID- 19378423
TI  - Effect of antioxidant supplementation on leucocyte expression of reactive oxygen
      species in athletes.
AB  - OBJECTIVE: Previous studies have shown that leucocytes, in particular
      granulocytes, have an enormous capacity for reactive oxygen species (ROS)
      production, and that this can be influenced by the physical activity of the
      individual. Theoretically, endurance-trained athletes could profit by increasing
      their intake of antioxidants, thus neutralizing increased ROS production. The aim
      of the present investigation was to study the effect of dietary antioxidant
      supplementation on leucocyte ROS expression and total plasma antioxidant status
      (TAS) in endurance-trained athletes over the course of 4 weeks. METHODS: Eighteen
      athletes were recruited for the study. A randomized, double-blinded, placebo
      controlled crossover study of 4 weeks of antioxidant supplementation (BiO
      Antioxidant 2.1 (400 mg vitamin C and 180 mg vitamin E d(-1)) and BiO-Quinon Q10
      (200 mg d(-1) was performed. Flow cytometry was applied to examine the leucocyte
      expression of ROS using the ROS-sensitive probes dihydroethidium and
      dihydrorhodamine 123. The Randox Total Antioxidant Status kit was used to measure
      the plasma TAS of the athletes. RESULTS: After 4 weeks of antioxidant
      supplementation, we observed no significant differences in ROS levels in
      granulocytes and monocytes either basally or after in vitro stimulation with
      phorbol myristate acetate. Plasma TAS did not change significantly during the
      intervention period. CONCLUSIONS: We observed no influence of 4 weeks of dietary
      antioxidant supplementation on oxidative stress status. Based on these findings,
      there is no rationale advising athletes to ingest antioxidant supplements in
      addition to their regular diet if that includes daily recommended doses of
      vitamins.

PMID- 19378424
TI  - C-reactive protein and tumor necrosis factor-alpha in relation to insulin
      mediated glucose uptake, smoking and atherosclerosis.
AB  - OBJECTIVES: To examine the hypothesis that serum concentration of C-reactive
      protein (CRP) is inversely associated with insulin sensitivity and obesity, and
      that this may by mediated by tumor necrosis factor-alpha (TNFalpha) and
      interleukin-6 (IL-6). MATERIAL AND METHODS: Cross-sectional, one-center study of
      a population-based sample of 58-year-old Swedish men (n = 98). Exclusion criteria
      were cardiovascular disease, clinical diabetes mellitus and/ or continuous
      cardiovascular medication. Glucose infusion-rate (euglycemic hyperinsulinemic
      clamp), adjusted for fat-free mass, which together with total body fat was
      measured by dual-energy X-ray absorptiometry. Serum concentrations of CRP,
      TNFalpha, soluble TNFalpha receptor 2 (sTNFAR2), IL-6 determined by ELISA.
      Ultrasound was used to measure intima-media thickness (IMT) in both common
      carotid arteries, carotid bulbs and in the right femoral artery. RESULTS: CRP was
      inversely associated with insulin sensitivity (r = -0.28, p < 0.01) and with
      total body fat (r = 0.31, p < 0.01), but not independently of the TNFalpha and
      sTNFAR2 product. Serum CRP, TNFalpha, sTNFAR2, but not IL-6, were associated with
      low insulin sensitivity, total body fat, abdominal obesity, hyperinsulinemia,
      hypertriglyceridemia, low HDL cholesterol and small LDL particles, i.e. the
      metabolic syndrome. These associations were independent of smoking and carotid
      and femoral artery IMT. CONCLUSIONS: Serum concentrations of CRP were related to
      insulin sensitivity and accompanying factors constituting the metabolic syndrome.
      The results indicate that this association may be mediated by adipose tissue and
      TNFalpha effects, the latter measured as the product of TNFalpha and sTNFAR2.
      This was a cross-sectional study and causality cannot be proven.

PMID- 19378425
TI  - Carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 19
      (CYFRA 21-1) levels in induced sputum of lung cancer patients.
AB  - OBJECTIVES: The diagnosis of lung cancer is usually based on the histological and
      cytological examination of material obtained by bronchoscopy. Tumour markers in
      serum are of little use as a diagnostic tool for lung cancer. We hypothesized
      that induced sputum could be a suitable material for measuring tumour markers
      and, accordingly, attempted to evaluate the diagnostic value of such measurements
      in lung cancer. Induced sputum is minimally invasive and readily obtainable.
      MATERIAL AND METHODS: Fifty patients with lung cancer and 24 subjects with
      chronic obstructive pulmonary disease (COPD) were included in the study. CEA, NSE
      and CYFRA 21-1 levels in serum and induced sputum were measured by
      immunoradiometric assays. RESULTS: Serum and sputum CEA, serum and sputum NSE and
      serum CYFRA 21-1 did not differ significantly between lung cancer and COPD
      patients. Sputum CYFRA 21-1 was 7 times greater in the lung cancer group than in
      the COPD group. This finding was true in both small cell (SCLC) and non-small
      cell (NSCLC) lung cancer. The sensitivity, specificity, positive and negative
      predictive values were 86, 75, 88 and 72%, respectively. CONCLUSION: Of tumour
      markers in induced sputum, sputum CYFRA 21-1 offered the best predictive values,
      although not sufficiently satisfactory to suggest its routine use in lung cancer
      diagnosis.

PMID- 19378426
TI  - Inflammatory responses after percutaneous coronary intervention in patients with
      acute myocardial infarction or stable angina pectoris.
AB  - OBJECTIVE: To investigate the profile of circulating inflammatory markers after
      percutaneous coronary intervention (PCI) in patients with AMI or stable angina
      pectoris (AP). MATERIAL AND METHODS: Twenty patients with AMI and 10 with stable
      AP were treated with PCI of a central coronary artery. Blood samples were drawn
      immediately before PCI, in the AP group and after 3 and 12 h, days 1, 3, 5, 7 and
      14 in both groups. RESULTS: Interleukin 6 increased in both groups to time-point
      12 h and day 1 (peak), being significantly higher in the AMI group compared to
      the AP group at 3 and 12 h, and also at days 1 and 3. A similar profile was
      demonstrated for CRP with significantly higher levels in the AMI group at days 1,
      3 and 5 compared to the AP group. A slightly different pattern was shown for
      Interleukin 10 (IL-10) with significantly higher levels in the AMI group at 3 and
      12 h, days 1 and 14 compared to the AP group. CONCLUSION: AMI patients treated
      with PCI experienced a marked short-term increase in pro-inflammatory mediators
      as well as IL-10 compared to patients with stable angina pectoris treated with
      PCI.

PMID- 19378427
TI  - Biochemical characterization of four novel mutations in the thyroid hormone
      receptor beta gene in patients with resistance to thyroid hormone.
AB  - In resistance to thyroid hormone (RTH), decreased tissue responsiveness to
      thyroid hormones is usually caused by mutations in the thyroid hormone receptor
      beta (THRB) gene. Subsequently, in serum the level of thyroid stimulating hormone
      (TSH) is not suppressed despite increased concentrations of thyroxine (T4) and
      triiodothyronine (T3). In our laboratory, DNA sequences of exon 7 to 10 in the
      THRB gene have been analysed in individuals with biochemical signs of RTH. Four
      novel point mutations were identified (I250T, A279E, T327A and L440P) and their
      effects on T3 binding activity characterized. The mutations were introduced into
      a vector carrying the wild-type THRB cDNA by in vitro mutagenesis. T3-binding
      activity was measured by a filter-binding assay procedure in receptors generated
      from the vector by in vitro transcription and translation. Specific binding was
      calculated as total activity subtracted by non-specific activity. The association
      constants (Ka) of the wildtype (WT) and mutant receptors were determined by
      Scatchard analysis. No specific T3-binding was observed for the receptor with the
      A279E mutation. The binding affinity was reduced by 74% in the T327A mutant and
      by about 50% in the I250T and L440P mutants compared to the WT receptor (Ka = 4.2
      x 10(10) L/mol). The reduction of T3-binding affinity caused by the four
      mutations in our study is comparable to the effects of THRB gene mutations found
      in other patients with RTH and supports the assumption that the signs of RTH
      observed in our patients are caused by the mutations.

PMID- 19378428
TI  - The Lund-Malmo creatinine-based glomerular filtration rate prediction equation
      for adults also performs well in children.
AB  - OBJECTIVE: To evaluate the clinical performance in a paediatric population of the
      Lund-Malmo creatinine-based glomerular filtration rate (GFR) prediction
      equations, primarily developed for adults. MATERIAL AND METHOD: Iohexol clearance
      was used as the gold standard in 85 paediatric Caucasian patients (0.3-17 years;
      37 F/48 M). One Lund-Malmo equation was based on age and gender (LM) and one
      included lean body mass (LM-LBM). Comparisons focused on correlation (adjusted
      R2), bias (median percent error) and accuracy (proportions of predicted GFR
      differing < or = 30% from measured GFR) (mL/min/1.73 m2). The performances were
      compared with those of the Modification of Diet in Renal Disease (MDRD) Study
      equation, a dedicated paediatric creatinine equation, Counahan-Barratt (CB) and a
      cystatin C-based equation. RESULTS: The MDRD equation performed poorly with a
      median bias of 96%. Of the remaining equations, only the LM-LBM produced
      significant bias (+10% in median) according to line of identity regression
      analysis. The LM equation yielded marginally higher accuracy (76%) than the LM
      LBM equation (74%) and the CB (73%), but lower than the cystatin C-based equation
      (82%). However, the estimated accuracy figures for these four equations were
      generally imprecise and none of the differences compared with the LM equation was
      statistically significant. CONCLUSION: In contrast to most creatinine-based GFR
      prediction equations, the LM equation performs adequately for both children and
      adults. This may be due to the unique model-building principles used when the LM
      equation was established. Further validation in a larger paediatric population is
      necessary.

PMID- 19378429
TI  - Use of capillary electrophoresis for accurate determination of CAG repeats
      causing Huntington disease. An oligonucleotide design avoiding shadow bands.
AB  - Huntington disease (HD) is a neurodegenerative disorder associated with the
      expansion of a polymorphic trinucleotide CAG repeat in the HD gene. We have
      developed an assay to accurately determine CAG repeats that combines a novel
      oligonucleotide design and the resolution of capillary electrophoresis. A
      mismatch in the second nucleotide from the 3' end enhanced specificity by
      avoiding mispriming and diminishing shadow bands and artifactual PCR products.
      The coupling of capillary electrophoresis analysis with the assay added the
      advantages of accuracy, high resolution, semi-automation, rapid analysis and low
      sample consumption. Analysis of 200 chromosomes in the Spanish population sample
      studied (control group) gave a peak frequency for 16 CAG repeats and of 7
      triplets for CCG repeats. Diagnosis of HD was confirmed in 22 of 34 individuals
      with a range of CAG repeats from 39 to 52. Predictive testing was also carried
      out for 19 relatives of the HD families diagnosed at our laboratory. The method
      proposed in this article provides an accurate sizing of DNA repeats that can be
      applied to the analysis of DNA size-related disorders.

PMID- 19378430
TI  - Cyclosporin A pre-incubation attenuates hypoxia/reoxygenation-induced apoptosis
      in mesenchymal stem cells.
AB  - Although mesenchymal stem cells (MSCs) are being tested for cardiac repair, the
      majority of transplanted cells undergo apoptosis in the ischaemic heart because
      of the effects of ischaemia/reperfusion, poor blood supply and other pro
      apoptotic factors. Several experimental and clinical studies have suggested that
      cyclosporin A (CsA) treatment reduces apoptosis in human endothelial cells and
      neurocytes. However, the effect of CsA on the apoptosis in MSCs is still unclear.
      In this study, we investigated whether CsA could inhibit hypoxia/ reoxygenation
      (H/R)-induced apoptosis in MSCs. MSCs pre-incubated with or without CsA were
      subjected to 6 h of hypoxia followed by 12 h of reoxygenation. Our data showed
      that pre-incubation with 0.5-5 microM CsA dose-dependently protected the MSCs
      from H/R injury, as evidenced by decreased apoptosis and increased cell
      viability. CsA inhibited the H/R-induced translocation of cytochrome c, increased
      bcl-2 expression and restored mitochondrial membrane potential. CsA also
      increased the expression of p-BAD. We propose that preincubation MSCs with CsA
      inhibits MSC apoptosis through the mitochondrial and BAD pathway.

PMID- 19378431
TI  - Inflammation and oxidative stress are associated differently with endothelial
      function and arterial stiffness in healthy subjects and in patients with
      atherosclerosis.
AB  - Inflammation and oxidative stress (OxS) play key roles in atherogenesis; however,
      their causal relationship is not yet completely understood. Much attention has
      been given to the possibility that inflammation is a primary process of
      atherosclerosis and that OxS may be a by-product of the inflammatory process. We
      hypothesized, accordingly, that chronic systemic inflammation affects endothelial
      vasomotor function in the subclinical condition, whereas oxidative modifications
      are more involved in the structural stiffening of the arteries in
      atherosclerosis. The aim of our study was to test this hypothesis. Endothelial
      function and arterial stiffness were assessed non-invasively by pulse wave
      analysis, and blood/urinary samples were taken in 39 patients with peripheral
      arterial disease as well as in 34 controls. The patients showed significantly
      reduced endothelial function index (EFI) and increased augmentation index (AIx),
      as well as higher estimated aortic pulse wave velocity (PWV) and elevated values
      of the intercellular adhesion molecule-1 (ICAM-1), high sensitivity C-reactive
      protein, myeloperoxidase and urinary 8-iso-prostaglandin F2a (F2-IsoPs). There
      was an inverse association between EFI and ICAM-1 (R = -0.44, p = 0.009) in the
      controls, but not in the patients. Augmentation index and estimated aortic PWV
      correlated with F2-IsoPs only in the patients (R = 0.5, p = 0.001; R = -0.43, p =
      0.006, respectively). After controlling for potential confounders, these
      associations remained significant. The study demonstrates that impairment of
      endothelial vasomotor capacity is affected by degree of inflammation in the
      subclinical condition, whereas arterial stiffening is determined by level of
      oxidative modifications in atherosclerosis.

PMID- 19378432
TI  - Peritumoral TNFalpha administration influences tumour stroma structure and
      physiology independently of growth in DMBA-induced mammary tumours.
AB  - BACKGROUND: Systemic treatment of malignancies with high doses of tumour necrosis
      factor-alpha (TNFalpha) has an anticancer effect, but also serious side effects.
      The aim of the present study was to elucidate the effects of local TNFalpha
      administration alone or in combination with chemotherapy on tumour stroma
      structure and physiology in di-methyl-benz-anthracene (DMBA)-induced mammary
      carcinomas in rats. METHODS: TNFalpha (500 ng/mL in a volume of 5 microL) was
      given s.c. around the carcinoma and 5-fluorouracil (5-FU) (1.5 mg/kg, volume of
      0.2 mL) was given i.p on days 1, 4, 7 and 10. RESULTS: Treatment with TNFalpha
      resulted in a significant reduction of tumour interstitial fluid pressure (TIFP:
      75-87%, p < 0.02-0.001), as well as in the number of tumour-infiltrating
      macrophages, extracellular volume (ECV) and collagen fibril density in carcinoma.
      In addition, pH was lowered in tumours treated with TNFalpha, suggesting
      decreased aerobic metabolism. Treatment with TNFalpha, however, had no effect on
      tumour growth, arterial blood pressure, tumour vessel density, plasma volume or
      body weight. Concentrations of locally produced VEGF and IL-1beta in carcinoma
      interstitial fluid or in serum were not affected by TNFalpha. The study
      demonstrated that these cytokines are produced locally in the tumour.
      Furthermore, TNFalpha had no effect on efficacy of treatment with 5-FU.
      CONCLUSIONS: Locally administered TNFalpha did not affect DMBA-induced mammary
      tumour growth or vasculature, but reduced inflammation and ECM structure,
      suggesting the latter to be of importance in the observed reduction in TIFP.

PMID- 19378433
TI  - D-dimer as a predictor of the need for laparotomy in patients with unclear non
      traumatic acute abdomen. A preliminary study.
AB  - OBJECTIVE: The acute onset of intense abdominal pain requires rapid evaluation,
      and since D-dimer level is reported to be useful in the diagnosis of patients
      with suspected acute superior mesenteric artery occlusion, our aim was to
      evaluate the value of D-dimer testing in the diagnosis of acute surgical abdomen
      with no precise diagnosis. MATERIAL AND METHODS: Between July 2004 and June 2006,
      93 patients with acute abdomen who required surgical exploration without precise
      diagnosis were admitted to this prospective clinical study. After surgery, the
      patients were divided into two groups: group 1 (n=52), patients who needed
      immediate laparotomy, and group 2 (n=41), patients without the need for
      laparotomy. Blood samples were taken to analyse D-dimer, white blood cell count
      and pH level. P-values of <0.05 were considered statistically significant.
      RESULTS: There was a positive correlation between the plasma D-dimer level and
      leucocyte count. Leucocyte counts > 16,800/mm3 (p < 0.01) and D-dimer levels >4.7
      microg FEU/mL were more sensitive (p < 0.001). Sensitivity was 97.6% and
      specificity 61.5% for D-dimer level, and 82.9% and 42.3%, respectively, for
      leucocyte count. Metabolic acidosis at admission was the most important factor
      for mortality (p < 0.001). CONCLUSIONS: In a patient with acute abdomen without
      precise diagnosis, a D-dimer level above the cut-off value (4.7 microg fibrinogen
      equivalent units/mL) may be an indicator with high sensitivity for surgical
      pathology requiring laparotomy.

PMID- 19378434
TI  - Transient elevation of neutrophil proteinases in induced sputum during COPD
      exacerbation.
AB  - OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) are prone
      to acute exacerbations associated with increased morbidity and mortality. One
      potential group of enzymes causing tissue destruction in this disease includes
      neutrophil proteinase elastase (NE), collagenase-2 (matrix metalloproteinase-8
      (MMP-8)) and gelatinase B (MMP-9). We investigated the activity of NE and the
      levels of MMP-8 and MMP-9 in a longitudinal setting at and after COPD
      exacerbation using a non-invasive technique, i.e., induced sputum, to ascertain
      whether these proteinases play a role in COPD exacerbation. MATERIAL AND METHODS:
      The study included healthy non-smokers (n=32), healthy smokers (n=28), patients
      with stable COPD (n=15), COPD patients with acute exacerbations (exa) (n=10) and
      their recovery (n=8) after 4 weeks. NE activity by synthetic peptide substrate
      and spectrophotometry, MMP-8 levels by immunofluorometry and MMP-9 levels by
      ELISA were analysed from induced sputum supernatants. RESULTS: NE activity and
      the level of MMP-8 increased highly significantly in patients with COPD
      exacerbation compared to stable COPD and controls (NE: p = 0.001 and p < 0.0001;
      MMP-8: p < 0.001 and p < 0.0001). Paired samples showed a decrease of these
      proteinases during the recovery period after exacerbation (p = 0.03, p = 0.04).
      The proteinase levels correlated not only with the percentage and number of
      neutrophils but also with the lung function parameters (FEV1/FVC and diffusion
      capacity). CONCLUSIONS: COPD exacerbations are associated with neutrophil
      recruitment into the airways but also transient activation and/or elevation of
      tissue destruction proteinases, such as NE and MMP-8, which can be detected from
      the induced sputum supernatants of these COPD patients.

PMID- 19378435
TI  - Variations in prostate-specific antigen free/total ratio in acute stress.
AB  - Serum prostate-specific antigen complexed to alpha2-macroglobulin is occult and
      is not detected by conventional immunoassays. Conditions affecting alpha2
      macroglobulin levels may alter the specificity of prostate-specific antigen
      free/total ratio in predicting prostate cancer. A group of patients (n=24)
      undergoing surgical stress due to a coronary artery bypass grafting was followed
      pre- and postoperatively up to 6 days. Total and free prostate-specific antigen,
      alpha2-macroglobulin, and C-reactive protein were measured by
      electrochemiluminescence, immunonephelometry, and immunoturbidimetry,
      respectively. Total prostate-specific antigen and C-reactive protein increased
      significantly postsurgery and remained elevated. Free/total ratio correlated
      negatively with C-reactive protein only (p = 0.000) using xtgee panel data
      analysis, after correction for plasma volume changes using albumin. Increased C
      reactive protein may reflect falsely decreased free/total ratio. Therefore,
      prostate-specific antigen free/total ratio would be more reliable if interpreted
      in combination with information about CRP. However, it is recommended to defer
      the measurement of free/total ratio if CRP is highly elevated.

PMID- 19378436
TI  - Sustained postprandial decrease in plasma levels of LDL cholesterol in patients
      with type-2 diabetes mellitus.
AB  - OBJECTIVE: Low density lipoprotein cholesterol (LDL-C) is an independent and
      modifiable risk factor for development of cardiovascular disease (CVD).
      Postprandial lipid metabolism has been linked to CVD, but little is known about
      the postprandial LDL-C profile in patients with type-2 diabetes (T2DM). We aimed
      to study the postprandial levels of LDL-C in T2DM patients. MATERIAL AND METHODS:
      After an overnight fast, 74 T2DM patients, mean age approximately 60 years, were
      served a standard fat-rich meal of 3515 kJ containing 54% fat, 13 % protein and
      33 % carbohydrates. Only drinking water was allowed postprandially. Blood samples
      were drawn at times 0 (fasting), 1.5, 3.0, 4.5 and 6.0 h (postprandial). In all
      samples, LDL-C was measured with modified beta quantification (separation by
      ultracentrifugation followed by measurement of infranate high density lipoprotein
      cholesterol (HLD-C) using a homogeneous assay). RESULTS: At all postprandial
      times, levels of LDL-C showed highly significant (p < 0.005) decreases compared
      to time 0 (mean [95% CI] maximum change in LDL-C levels at 3.0 h: -0.16 mmol/L [
      0.12; -0.20]; p < 0.001). Independently of fasting LDL-C levels and ongoing
      statin therapy, LDL-C decreased significantly more in female compared to male
      patients postprandially (mean [95% CI] maximum unadjusted change versus time 0 in
      LDL-C for men [n=56] at 3.0 h: -0.14 mmol/L [-0.19; -0.10], p < 0.001; for women
      [n=18] at 4.5 h: -0.26 mmol/L [-0.35; -0.18], p < 0.001; -0.14 mmol/L [-0.24; 
      0.05], p = 0.005 between genders for the mean [95% CI] fasting adjusted
      difference at 4.5 h in the change versus time 0 in LDL-C; gender by time
      interaction: p = 0.007 (repeated measures mixed model)). CONCLUSIONS: In T2DM
      patients served a fat-rich meal, levels of LDL-C decreased significantly more in
      women compared to men postprandially, irrespective of fasting levels or ongoing
      statin therapy. This might have implications in the atherosclerotic process and
      on any difference in the risk of CVD between genders.

PMID- 19378437
TI  - Impact of testosterone treatment on postprandial triglyceride metabolism in
      elderly men with subnormal testosterone levels.
AB  - OBJECTIVE: To investigate the impact of testosterone supplementation on
      postprandial triglycerides in elderly men with subnormal endogenous testosterone.
      MATERIAL AND METHODS: Twenty-six men with subnormal testosterone levels (< or =
      11.0 nmol/L) were randomly assigned to treatment with intramuscular testosterone
      or placebo for one year in a double-blinded study. The participants underwent an
      oral fat load before and after the treatment period, and serum and chylomicron
      triglyceride levels were measured fasting and 2, 4, 6 and 8 h afterwards,
      together with total fat mass and fat-free mass. RESULTS: Total testosterone rose
      to low-normal levels in the testosterone-treated group. No differences in waist
      circumference, body mass index, serum levels of total cholesterol, low-density
      lipoprotein cholesterol, high density lipoprotein cholesterol, fasting
      triglyceride concentrations or lipase activity between the groups were observed
      during testosterone treatment. Testosterone treatment did not affect postprandial
      serum and chylomicron triglyceride levels assessed by area under the curve,
      incremental area under the curve or triglyceride response. Total fat mass was
      significantly reduced (p <0.001) while fat-free mass was significantly increased
      (p < 0.001) in the testosterone-treated group. CONCLUSION: Normalizing
      testosterone levels in elderly men does not seem to affect the postprandial lipid
      metabolism to any great extent, but has favourable effects on body composition.

PMID- 19378438
TI  - Increased plasma levels of beta2-microglobulin, cystatin C and beta-trace protein
      in term pregnancy are not due to utero-placental production.
AB  - OBJECTIVE: To study concentration gradients of the low molecular mass proteins,
      beta2-microglobulin, cystatin C and beta-trace protein, between the uterine and
      ante-cubital veins, the umbilical artery and vein and in the amniotic fluid
      compartment. MATERIALS AND METHODS: The study comprised 27 healthy women with
      uncomplicated pregnancies undergoing caesarean section at term. Samples were
      collected simultaneously and paired t-tests were used to compare mean plasma
      concentrations. RESULTS: There was no significant concentration gradient in the
      plasma levels of beta2-microglobulin, cystatin C or beta-trace protein between
      the uterine and antecubital veins. There were no correlations between the protein
      levels in the compartments. CONCLUSION: The utero-placental unit does not
      contribute significantly to the maternal levels of beta2-microglobulin, cystatin
      C and beta-trace protein in normal pregnancy, and the proteins are not likely to
      be transferred across the placental barrier.

PMID- 19378439
TI  - A combined abnormality in heart rate variation and QT corrected interval is a
      strong predictor of cardiovascular death in type 1 diabetes.
AB  - OBJECTIVE: Long-term diabetes is associated with excess morbidity and mortality,
      and cardiovascular autonomic neuropathy and QTc interval abnormalities are both
      predictive of early cardiovascular death in diabetes. We aimed to investigate the
      effect of these risk factors in a large cohort of type 1 diabetic patients
      followed prospectively for 10 years. MATERIAL AND METHODS: Three-hundred-and
      ninety-one type 1 diabetic mellitus patients (240 M and 151 F, age 41.8 years +/-
      9.9 (mean +/-SD), duration of DM 27.3 years +/- 8.2) were followed in an
      outpatient setting. RESULTS: Patients with decreased heart rate variability had
      an excess overall mortality that diminished after adjusting for conventional
      cardiovascular risk factors; hazard ratio 2.5 (0.9-6.8; p = 0.071) compared to
      patients with normal heart rate variability. Likewise, prolonged QTc interval was
      associated with premature death with an adjusted hazard ratio of 2.3 (1.3-4.0; p
      = 0.005). In a combined analysis, patients with abnormal values for heart rate
      variability and QTc had a poorer prognosis compared to patients with normal test
      values for both parameters (adjusted hazard ratio 6.7 (1.8-25; p = 0.005)). Of
      the 34 patients with both test values abnormal, 15 died and 14 of these from
      cardiovascular causes. CONCLUSIONS: We conclude that combined abnormality in
      heart rate variability and QTc is a strong predictor of mortality in type 1
      diabetes independently of conventional risk factors. These results have
      implications for future screening and treatment programmes for cardiovascular
      disease in type 1 diabetes.

PMID- 19378440
TI  - Cardiac structure and function in a mouse model of uraemia without hypertension.
AB  - Kidney dysfunction is often associated with cardiac left ventricular hypertrophy
      and increased cardiovascular mortality. OBJECTIVE: The aim of this study was to
      find out whether this reflects direct effects of uraemia on the heart or is
      dependent on accompanying hypertension. MATERIAL AND METHODS: Apolipoprotein-E
      (apoE)-deficient C57BL/6 mice are resistant to development of hypertension after
      renal mass reduction. To evaluate the impact of uraemia without hypertension on
      the heart, apoE-deficient mice underwent 5/6 nephrectomy (NX) or sham operation
      (Sh) and were randomized to treatment with the angiotensin converting enzyme
      inhibitor enalapril (12 mg kg(-1) d(-1)) or no medication. RESULTS: NX did not
      affect systolic blood pressure (BP), but reduced mean creatinine clearance, body
      weight and blood haemoglobin to 27% (p < 0.01), 82% (p < 0.0001) and 73% (p <
      0.0001), respectively, of the values in Sh mice. Thirty-six weeks after NX, heart
      wet weight, echocardiographic estimates of left ventricular mass and left
      ventricular diastolic and systolic functions were similar in NX and Sh mice. NX
      did not increase cardiac fibrosis or cardiac mRNA expression of biglycan, whereas
      it decreased the mRNA expression of procollagen (p < 0.01). Enalapril reduced BP
      (p < 0.001), heart wet weight and estimated left ventricular mass in both NX (p <
      0.01) and Sh mice (p < 0.05), but did not affect cardiac diastolic or systolic
      function. Conclusions. The results suggest that uraemia does not impair cardiac
      structure or function in apoE-deficient mice. Since NX has no effect on BP in
      apoE-deficient mice, the results may indicate that hypertension is important for
      development of left ventricular disease in uraemia.

PMID- 19378441
TI  - Unhygienic male circumcision procedures and HIV transmission.

PMID- 19378442
TI  - Why are alcohol-related emergency department presentations under-detected? An
      exploratory study using nursing triage text.
AB  - INTRODUCTION AND AIMS: This study examined two methods of detecting alcohol
      related emergency department (ED) presentations, provisional medical diagnosis
      and nursing triage text, and compared patient and service delivery
      characteristics to determine which patients are being missed from formal
      diagnosis in order to explore why alcohol-related ED presentations are under
      detected. DESIGN AND METHODS: Data were reviewed for all ED presentations from
      2004 to 2006 (n = 118,881) for a major teaching hospital in Sydney, Australia.
      Each record included two nursing triage free-text fields, which were searched for
      over 60 alcohol-related terms and coded for a range of issues. Adjusted odds
      ratios were used to compare diagnostically coded alcohol-related presentations to
      those detected using triage text. RESULTS: Approximately 4.5% of ED presentations
      were identified as alcohol-related, with 24% of these identified through
      diagnostic codes and the remainder identified by triage text. Diagnostic coding
      was more likely if the patient arrived by ambulance [odds ratio (OR) = 2.35] or
      showed signs of aggression (OR = 1.86). Failure to code alcohol-related issues
      was more than three times (OR = 3.23) more likely for patients with injuries.
      DISCUSSION AND CONCLUSIONS: Alcohol-related presentations place a high demand on
      ED staff and less than one-quarter have an alcohol-related diagnosis recorded by
      their treating doctor. In order for routine ED data to be more effective for
      detecting alcohol-related ED presentations, it is recommended that additional
      resources such as an alcohol health worker be employed in Australian hospitals.
      These workers can educate and support ED staff to identify more clearly and
      record the clinical signs of alcohol and directly provide brief interventions.

PMID- 19378443
TI  - The impact of a parent-directed intervention on parent-child communication about
      tobacco and alcohol.
AB  - INTRODUCTION AND AIM: Given the likelihood of engaging in the hazardous use of
      tobacco and alcohol increases during teenage years, pre-adolescence is a critical
      time to implement prevention programmes. While social factors other than those
      associated with parenting play a role in determining a child's risk for
      initiation of tobacco and alcohol use, parents can have a significant influence
      on their children's decisions about these issues. The aim of this study was to
      assess the impact of an in-home parent-directed drug education intervention on
      parent-child communication about tobacco and alcohol. DESIGN AND METHODS: A group
      randomised intervention trial was conducted in Perth, Western Australia. Schools
      were selected using stratified random sampling and randomised to three study
      conditions. A total of 1201 parents of 10- 11-year-old children were recruited
      from 20 schools. The impact of a self-help intervention, comprised of five
      communication sheets containing information and activities designed to encourage
      parents to talk with their 10- 11-year-old child about issues related to smoking
      cigarettes and drinking alcohol, was assessed. RESULTS: Intervention-group
      parents were more likely to have spoken with their children, to have spoken more
      recently, to have engaged the child during the discussion and to have addressed
      the topics identified as being protective of children's involvement in tobacco
      and alcohol. In addition, the duration of talks about alcohol was longer than for
      parents in the comparison group. DISCUSSION AND CONCLUSIONS: Parents of 10- 11
      year-old children appear to be receptive to participating in a home-based drug
      related educational intervention and the parent-directed intervention seems to
      have enhanced parent-child tobacco- and alcohol-related communication.

PMID- 19378444
TI  - Process and predictors of drug treatment referral and referral uptake at the
      Sydney Medically Supervised Injecting Centre.
AB  - INTRODUCTION AND AIMS: Low-threshold drug services such as drug consumption rooms
      (DCRs) have been posited as referral gateways to drug treatment for injecting
      drug users (IDUs). We examined the process and predictors of drug treatment
      referral and referral uptake at an Australian DCR. DESIGN AND METHODS: We
      undertook behavioural surveillance of the Sydney Medically Supervised Injecting
      Centre (MSIC) client cohort between May 2001 and October 2002. Data were
      collected for 3715 IDUs on demographics, injecting and drug use behaviours at
      registration and all subsequent MSIC service utilisation, including referrals.
      Referral uptake (defined as presentation for assessment at the relevant agency)
      was traced via reply-paid postcards included with written referrals. RESULTS:
      Sixteen per cent of clients who received written referrals to drug treatment had
      confirmed drug treatment referral uptake. Factors associated with drug treatment
      referral were frequent MSIC attendance [adjusted odds ratios (AOR = 9.4], receipt
      of written health (AOR = 4.8) or psychosocial (AOR = 4.3) referrals, heroin as
      main drug injected (AOR = 1.9) and completion of high school education (AOR =
      1.6). Factors associated positively with drug treatment referral uptake were
      recent sex work (AOR = 2.6) and at least daily injection (AOR = 2.3). Previous
      psychiatric illness or self-harm was associated negatively with drug treatment
      referral uptake (AOR = 0.2). DISCUSSION AND CONCLUSIONS: MSIC engaged IDUs
      successfully in drug treatment referral and this was associated with presentation
      for drug treatment assessment and other health and psychosocial services. To
      improve rates of drug treatment referral and uptake, those with a history of
      mental health issues may require more intensive referral and case management.

PMID- 19378445
TI  - Increasing socio-economic inequalities in drug-induced deaths in Australia: 1981
      2002.
AB  - INTRODUCTION AND AIMS: Since the 1990s illicit drug use death rates in Australia
      have increased markedly. There is a notable gap in knowledge about changing socio
      economic inequalities in drug use death rates. Some limited Australian and
      overseas data point to higher rates of drug death in the lowest socio-economic
      groups, but the paucity of available studies and their sometimes conflicting
      findings need to be addressed. DESIGN AND METHODS: This paper uses data obtained
      from the Australian Bureau of Statistics (ABS) to examine changes in age
      standardised drug-induced mortality rates for Australian males over the period
      1981-2002. Socio-economic status was categorised as manual or non-manual work
      status. RESULTS: With the rapid increase in drug-induced mortality rates in the
      1990s, there was a parallel increase in socio-economic inequalities in drug
      induced deaths. The decline in drug death rates from 2000 onwards was associated
      with a decline in socio-economic inequalities. By 2002, manual workers had drug
      death rates well over twice the rate of non-manual workers. DISCUSSION: Three
      factors are identified which contribute to these socio-economic inequalities in
      mortality. First, there has been an age shift in deaths evident only for manual
      workers. Secondly, there has been an increase in availability until 1999 and a
      relative decline in the cost of the drug, which most often leads to drug death
      (heroin). Thirdly, there has been a shift to amphetamine use which may lead to
      significant levels of morbidity, but few deaths.

PMID- 19378446
TI  - Comparing heroin users and prescription opioid users in a Canadian multi-site
      population of illicit opioid users.
AB  - INTRODUCTION AND AIMS: Recent data suggest increasing prescription opioid and
      decreasing heroin use among street drug users, yet little is known on possible
      differential use characteristics and outcomes associated with these drugs. [While
      we recognise that, correctly, these populations would need to be labelled as
      opioid 'abusers' or 'non-medical users', we rely on the simpler terms 'use' and
      'users' for the population under study within the wider context of them being
      engaged overall in illicit opioid use activities.] This study compared drug use,
      health, and socio-economic characteristics between heroin (H)-only, prescription
      opioid (PO)-only and mixed heroin and prescription (PO & H) users in a Canadian
      multi-site cohort of illicit opioid and other drug users (OPICAN). DESIGN AND
      METHODS: Data from the most recent (2005) multi-component assessment of the H
      only (n = 94), PO-only (n = 304) and PO & H (n = 86) cohort sub-samples were
      analysed. Based on bivariate analyses of variables of interest, a multinomial
      logistic regression analysis (MLRA) model was computed, comparing PO-only and PO
      & H groups to the H-only reference group, respectively. RESULTS: H-only users
      were found in two of the seven study sites. Based on the MLRA, PO-only and PO & H
      users, compared to H-only users, were more likely to: be older, use
      benzodiazepines and cocaine, use drop-in shelters and less likely to use walk-in
      clinics. PO-only users were also more likely to: be white; receive legal income;
      use drugs by non-injection; have physical health problems; and use private
      physician services. DISCUSSION AND CONCLUSIONS: Our study underscores the
      increasing prevalence of PO compared to heroin use in the study population.
      Differences between PO-only and H-only users were more pronounced than
      differences between PO-only and PO & H users. PO-only use may be associated with
      lowered health risks and social burdens, yet concerns regarding polysubstance use
      and drug sourcing arise. Challenges for targeted interventions are discussed.

PMID- 19378447
TI  - Patterns of benzylpiperazine/trifluoromethylphenylpiperazine party pill use and
      adverse effects in a population sample in New Zealand.
AB  - INTRODUCTION AND AIMS: A large legal market for party pills containing
      benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) developed in
      New Zealand after 2004. The use of these party pills has been associated with
      adverse health effects. The purpose of this paper was to assess a general
      population sample of party pill users to investigate the relationship between (1)
      patterns of use of BZP/TFMPP party pills and concurrent use of other drug types,
      and (2) adverse side effects from BZP/TFMPP party pill use. DESIGN: A national
      household survey of the use of BZP/TFMPP party pills was conducted using a
      computer-assisted telephone interviewing (CATI) facility. The quantity of BZP and
      TFMPP in each brand of party pill was obtained from the National Poisons Centre.
      Multiple logistic regression analysis was used to identify independent predictors
      of having experienced adverse side effects from party pills. RESULTS: The mean
      quantity of BZP/TFMPP taken on an occasion of greatest use was 533 mg (median 400
      mg, range 43-2500 mg). Being female, using cannabis and other drugs concurrently
      with BZP/TFMPP party pills, taking large quantities of party pills in a single
      session and taking 5-hydroxytryptophan (5-HTP) recovery pills at the same time as
      party pills were independent predictors of having experienced an adverse problem
      from party pills. CONCLUSIONS: Females may be at greater risk of experiencing
      problems from BZP/TFMPP party pills due to their smaller physical size. Taking 5
      HTP 'recovery' pills with party pills may increase the risk of adverse effects as
      both substances increase users' levels of serotonin.

PMID- 19378448
TI  - Gender equality in university sportspeople's drinking.
AB  - INTRODUCTION AND AIMS: In large population-based alcohol studies males are shown
      consistently to drink more, and more hazardously, than females. However, research
      from some countries suggests that gender differences in drinking are converging,
      with females drinking more than in the past. Large population-based research may
      miss gender-based changes in drinking behaviours that occur in sub-populations
      most at risk of hazardous drinking. We examine gender differences in a sub
      population where hazardous drinking is common and endorsed, namely university
      sportspeople. DESIGN AND METHODS: The Alcohol Use Disorders Identification Test
      (AUDIT) and a drinking motives measure were used to assess hazardous drinking
      behaviours and drinking motives in 631 university sportspeople (females = 331,
      52%). RESULTS: There were no gender differences in AUDIT scores. However,
      drinking motives differed between genders, with coping motives being a
      significant predictor of hazardous drinking in females but not males. Hazardous
      drinking, including binge drinking (46.3%) and frequent binge drinking (35%), in
      New Zealand university sportspeople is high for both males and females.
      DISCUSSION AND CONCLUSIONS: New Zealand university sportspeople are one
      population where gender differences in drinking are not apparent and run counter
      to European population based research and research in US sporting populations.
      Gender role equality in the university systems, and endorsement of drinking in
      sporting culture, may account for the lack of gender differences in this New
      Zealand sporting population. Future research on gender differences in drinking
      should examine sub-populations where gender role differentiation is low, and
      socio-cultural/structural factors supporting gender equality are high.

PMID- 19378449
TI  - Acceptability of hepatitis C virus testing methods among injecting drug users.
AB  - INTRODUCTION AND AIMS: The acceptability of testing methods and procedures has
      implications for uptake of blood-borne virus screening in sentinel samples of
      injecting drug users (IDUs) likely to participate in surveillance. The aim of the
      current study was to determine the acceptability of three methods of hepatitis C
      virus (HCV) testing among injecting drug users (IDUs): oral fluid, capillary
      blood and venous blood sampling. DESIGN AND METHODS: A cross-sectional survey of
      IDUs was conducted in inner-city Sydney in 2005 for a laboratory validation study
      of HCV antibody testing. Participants were tested using the three different
      specimen collection methods and asked about the acceptability of each method and
      a particular preference documented. RESULTS: Two-hundred and twenty-nine IDUs
      participated in the study. Before and after specimen collection, the
      acceptability of all three collection methods for HCV testing was high (> 85%).
      Oral fluid remained the preferred method after sample collection, with females
      (65%) significantly more likely than males (49%) to report a preference
      (unadjusted odds ratio 2.0; 95% confidence interval 1.1-3.5, p = 0.03) for that
      method. DISCUSSION AND CONCLUSIONS: Findings suggest that oral fluid testing is
      an acceptable and preferred alternative for HCV testing among IDUs. However,
      concerns reported by participants in the study indicate that information and
      education regarding the nature and diagnostic value of oral fluid testing is
      necessary prior to its implementation for surveillance purposes among this
      population.

PMID- 19378450
TI  - Satisfaction guaranteed? What clients on methadone and buprenorphine think about
      their treatment.
AB  - INTRODUCTION AND AIMS: A consumer satisfaction survey was conducted among clients
      receiving methadone or buprenorphine treatment for opioid dependence. The survey
      aimed to assess client perceptions across a number of treatment domains,
      including the clinic environment, service provision, clinical relationships,
      medication and treatment outcomes. DESIGN AND METHODS: Participants were 432
      clients receiving treatment at nine public clinics in New South Wales, Australia.
      An interviewer-administered questionnaire was utilised, designed by the
      researchers. Participation was voluntary and anonymous. All participants received
      $10 remuneration. RESULTS: Seventy-eight per cent of participants were on
      methadone treatment. Overall satisfaction with treatment was high (mean: 3.8;
      very satisfied = 5). Participants were mainly satisfied with service provided by
      the clinic, although had concerns over the inflexibility associated with the
      clinic atmosphere, frequency of clinic attendance, dosing hours and lack of
      takeaway doses. While relationships with prescribers and case managers were rated
      positively, 16% and 21% of participants wanted to see their prescriber and case
      manager more often, respectively; 53% reported that they did not have input into
      their care plan. Regarding the helpfulness of case managers in assisting clients
      with problems experienced in identified domains of case management (e.g. drug
      use, physical and mental health, psychosocial supports), the mean rating was 5.2
      (excellent = 10). DISCUSSION AND CONCLUSIONS: While participants reported being
      mainly satisfied with their treatment, results must be viewed within the context
      of what a consumer reasonably expects to receive from a service. The concept of
      'expectation' and 'relative experience' is crucial in measuring consumer
      satisfaction among pharmacotherapy consumers.

PMID- 19378451
TI  - Incarceration experiences in a cohort of active injection drug users.
AB  - BACKGROUND: Incarceration has been associated with a number of health-related
      harms among injection drug users (IDU). However, little is known about the
      prevalence and correlates of incarceration among community-based samples of IDU.
      METHODS: We examined the prevalence and correlates of recent incarceration among
      IDU in the Scientific Evaluation of Supervised Injecting (SEOSI) cohort examined
      between 1 July 2004 and 30 June 2006 using generalised estimating equations
      (GEE). RESULTS: A total of 902 individuals were included in the analysis, of whom
      255 (28.72%) were female and 536 (59.42%) reported a history of incarceration. In
      a multivariate GEE model, recent incarceration was associated positively and
      independently with a number of high-risk drug using behaviours, including syringe
      sharing. CONCLUSIONS: An alarmingly high proportion of active IDU reported recent
      incarceration and injecting while incarcerated. Recent incarceration was
      associated independently with syringe sharing. These findings add further
      evidence to repeated demands for an expansion of appropriate harm-reduction
      measures in Canada's prisons.

PMID- 19378452
TI  - Fighting infection fly-style.

PMID- 19378453
TI  - Integrating insulin signaling and stress responses.

PMID- 19378454
TI  - Insights into physiology of aging and novel ways to increase lifespan.

PMID- 19378455
TI  - New advances in signaling and pattern formation.

PMID- 19378456
TI  - We hold these truths to be self-evident, that all flies and men are created
      equal: Recent progress on human disease models.

PMID- 19378457
TI  - New tools, resources for gene regulatory analysis in Drosophila.

PMID- 19378458
TI  - Cell cycle regulation.

PMID- 19378459
TI  - Dissecting the lean, mean, breeding machine.

PMID- 19378460
TI  - Behavioral, physiological, and cellular responses following trophic transfer of
      toxic monoaromatic hydrocarbons.
AB  - The trophic transfer of monoaromatic hydrocarbons to predatory organisms feeding
      upon contaminated marine animals is not well reported within the scientific
      literature. Branched alkylbenzenes (BABs) unresolved by gas chromatography have
      been reported to be principal toxic components of bioaccumulated hydrocarbons in
      the tissues of some wild mussel, Mytilus edulis, populations with poor health
      status. Mussels, M. edulis, contaminated with a commercial mixture of BABs were
      fed to shore crabs, Carcinus maenas, for 7 d, and effects upon the behavior,
      heart rate, hemolymph cellular viability, and immune response of the crabs were
      assessed. Accumulation of BABs in crab midgut gland tissue was quantified by gas
      chromatography-mass spectrometry, and the presence of BABs in crab urine was
      detected spectrophotometrically using ultraviolet fluorescence spectroscopy.
      Analysis of crab tissues and urine revealed a proportion of the BABs was
      transferred from the mussel tissues to the crabs, but the majority was not
      present 3 d after consumption of the mussels and may have been metabolized,
      excreted, or both. The results do not support the hypothesis that BABs are likely
      to be biomagnified, at least by crabs, in the marine environment. Alterations to
      measured cellular and physiological responses of crabs fed BAB-exposed mussels
      were not significant. Consumption of contaminated mussels was shown to cause
      highly significant abnormal behavior that, in the wild, may affect the feeding
      ability of crabs and make them more vulnerable to predation.

PMID- 19378461
TI  - Omega-3 and BDNF regulation: eicosapentaenoic acid may play a key role in
      limitation of CNS injury.

PMID- 19378462
TI  - Time-dependent effects of global cerebral ischemia on anxiety, locomotion, and
      habituation in rats.
AB  - Although changes in emotionality represent common features of post-ischemic
      recovery in humans, little is known about the effects of global cerebral ischemia
      on standard behavioral measures of emotionality in rodents. The present study
      investigated anxiety, locomotor activity, and habituation in test-naive ischemic
      (subjected to 10 min global ischemia) and sham-operated rats tested 1, 5, 15, and
      30 days post-reperfusion in the elevated plus-maze and the open-field. Although
      rats tested on day 1 post-reperfusion showed increased anxiety relative to sham
      operated controls, they demonstrated decreased anxiety on day 5. Anxiety levels
      were normal on days 15 and 30 following ischemia. Similarly, time-dependent
      changes in locomotor activity were observed with ischemic rats showing increased
      activity level on days 1, 5, and 30 post-reperfusion. Surprisingly, locomotor
      activity was suppressed at day 15. Habituation deficits in the open-field were
      apparent only on day 1 despite the lack of CA1 neuronal degeneration at this time
      interval. These findings suggest that both the nature and extent of the effects
      of global ischemia on behavioral measures of emotionality, locomotion, and
      habituation in rats are time-dependent.

PMID- 19378463
TI  - Functional differentiation and cooperation among the hippocampal subregions in
      rats to effect spatial memory processes.
AB  - We investigated the roles of the hippocampal subregions and intrahippocampal
      networks in effecting spatial reference and working processes. The results showed
      that the dentate gyrus plays a key role in encoding both types of spatial memory.
      Lesions in the dentate gyrus caused severe impairment in the acquisition of the
      Morris water maze and delayed matching-to-place tasks as compared to those in the
      other hippocampal subregions (Exp. 1). Further, there was functional cooperation
      between CA3 and CA1 via the Schaffer collaterals and the hippocampal commissure
      in the performance of both types of spatial memory tasks. Among the rats with
      intact hippocampal commissure, those with both contralateral and ipsilateral
      CA1/CA3 lesions showed a similar performance (Exp. 2A); however, among the rats
      with transected hippocampal commissure, those with the contralateral CA1/CA3
      lesions showed a more disruptive performance than the rats with the ipsilateral
      CA1/CA3 lesions (Exp. 2B). This study suggests that the hippocampus is the
      functional unit for spatial reference and working memory processes, including
      differential functions and functional cooperation among the hippocampal
      subregions.

PMID- 19378464
TI  - Amphetamine-evoked rotation requires newly synthesized dopamine at 14 days but
      not 1 day after intranigral 6-OHDA and is consistently dissociated from
      sensorimotor behavior.
AB  - Immediately after unilateral, intranigral 6-hydroxydopamine (6-OHDA), amphetamine
      (AMPH) evokes "paradoxical" contraversive rotation, whereas 14 days later, AMPH
      evokes the traditional ipsiversive rotation used to model the chronic
      Parkinsonian state. In this study, the hypothesis was that accelerated dopamine
      (DA) synthesis ipsilateral to the lesion augments cytoplasmic DA to produce
      paradoxical rotation. Therefore, the sensitivity to synthesis inhibition of AMPH
      evoked rotation at 1 or 14 days after 6-OHDA was assessed. To determine the
      functional status that might be reflected by paradoxical rotation, sensorimotor
      abilities were examined at 1 and 14 days following unilateral 6-OHDA using the
      elevated swing, paw placement, grip strength, ladder walking, somatosensory
      neglect, and cylinder tests. At 14 days after 6-OHDA when AMPH-evoked ipsiversive
      rotation is mediated by the intact hemisphere, rotation was dose-dependently
      reduced by tyrosine hydroxylase (TH) inhibition with alpha-methyl-p-tyrosine
      (alpha-MPT) or dopa decarboxylase (DDC) inhibition with 3-hydroxybenzyl hydrazine
      (NSD-1015), indicating dependence upon newly synthesized DA. Conversely, at 1 day
      after 6-OHDA, paradoxical rotation, presumably mediated by the treated
      hemisphere, was completely resistant to synthesis blockade, indicating an
      abundant supply of intracellular DA that is independent from synthesis rates.
      Sensorimotor behaviors were not correlated with AMPH-evoked rotation. The present
      data do not support the hypothesis that enhanced DA synthesis is required to
      express paradoxical rotation. Therefore, alternative mechanisms that may enhance
      cytoplasmic DA to produce paradoxical rotation are discussed.

PMID- 19378465
TI  - Two new test methods to quantify motor deficits in a marmoset model for
      Parkinson's disease.
AB  - The validity of the common marmoset (Callithrix jacchus) as a model for human
      disease depends on the development of parameters with clinical relevance. We
      tested the effect of treatment with MPTP in two newly developed non-invasive
      motor behavioral paradigms in the context of Parkinson's disease. The "Tower" was
      designed to quantify the marmoset's natural jumping behavior as a measure for
      akinesia, the "Hourglass" to test the marmoset's natural righting reflex as
      measure for rigidity, analogous to axial motor behavior in humans. MPTP treatment
      affected marmoset behavior in both testing paradigms. The marmoset's righting
      reflex in the Hourglass remained significantly impaired during the full 3-week
      period after the MPTP intoxication. In the Tower, the marmosets were not able to
      jump the largest distances one week after MPTP and showed a persistent reduction
      in activity during the 3-week period after the MPTP intoxication. Because not all
      aspects of motor behavior are similarly affected by MPTP, a complete behavioral
      sketch of parkinsonian marmosets should preferably include a range of motor
      behavior functions to create an overview of the full range of motor impairments.
      Both the Hourglass and Tower test provide important behavioral parameters in a
      clinically relevant multiple testing approach in motor disorder models.

PMID- 19378466
TI  - Neonatal maternal separation alters reward-related ultrasonic vocalizations in
      rat dams.
AB  - We examined the effects of brief or long durations of repeated maternal
      separation (MS) on ultrasonic vocalizations (USVs) in rat dams. 50-kHz USVs
      putatively identified as maternal in origin were emitted only immediately after
      pups were returned following MS. Maternal USV emission also depended on
      separation duration and pup age. Given that 50-kHz USVs are emitted in response
      to rewarding stimuli, MS may induce duration-dependent effects on maternal
      positive affect.

PMID- 19378467
TI  - Assessment of the renal toxicity of novel anti-inflammatory compounds using 
      cynomolgus monkey and human kidney cells.
AB  - PF1, an anti-inflammatory drug candidate, was nephrotoxic in cynomolgus monkeys
      in a manner that was qualitatively comparable to that observed with the two
      previous exploratory drug candidates (PF2and PF3). Based on the severity of
      nephrotoxicity, PF1 ranked between the other two compounds, withPF2 inducing
      mortality at all doses and PF3 eliciting only mild nephrotoxicity. To further
      characterize nephrotoxicity in monkeys and enable direct comparisons with humans,
      primary cultures of proximal tubular (PT) cells from monkey and human kidneys
      were used as in vitro tools, using lactate dehydrogenase release as the biomarker
      of cytotoxicity. In both human and monkey PT cells, PF2was by far the most
      cytotoxic compound of the three drugs. PF1 exhibited modest cytotoxicity at the
      highest concentration tested in human PT cells but none in monkey kidney cells
      whereas PF3 exhibited the reverse pattern.Because these drugs are organic anions,
      mechanistic studies using human organic anion transporters 1 and 3 (hOAT1
      andhOAT3) transfected cell lines were pursued to evaluate the potential of these
      compounds to interact with these transporters. All three drugs exhibited high
      affinity for hOAT3 (PF1 exhibited the lowest IC50 of 6M) but only weakly
      interacted with hOAT1 (with no interaction found for PF2). PF2 was a strong hOAT3
      (not hOAT1) substrate, whereas PF1 and PF3 were substrates for both hOAT1 and
      hOAT3.Upon pretreatment of monkeys with the OAT substrate probenecid, PF3
      systemic exposure (AUC) and half-life (t1/2) increased approximately 2-fold
      whereas clearance (CL) and volume of distribution (Vdss) decreased, as compared
      to naive monkeys. This indicated that PF3 competed with probenecid for hOAT1
      and/or hOAT3mediated elimination of PF3. Thus, hOAT1 and/or hOAT3 may be
      responsible for the uptake of this series of drugs in renal PT cells, which may
      directly or indirectly lead to the observed nephrotoxicity in vivo.

PMID- 19378469
TI  - 'Sudden Cardiac Death' makes the headline, but 'Football for Health' is the
      message.

PMID- 19378470
TI  - 12 ways to cut health care costs.  How you can rein in health care bills--yours
      and society's.

PMID- 19378468
TI  - Underlying mechanism of actions of tefluthrin, a pyrethroid insecticide, on
      voltage-gated ion currents and on action currents in pituitary tumor (GH3) cells
      and GnRH-secreting (GT1-7) neurons.
AB  - Tefluthrin is a synthetic pyrethroid and involved in acute neurotoxic effects.
      How this compound affects ion currents in endocrine or neuroendocrine cells
      remains unclear. Its effects on membrane ion currents in pituitary tumor (GH3)
      cells and in hypothalamic (GT1-7) neurons were investigated. Application of Tef
      (10 microM) increased the amplitude of voltage-gated Na+ current (INa), along
      with a slowing in current inactivation and deactivation in GH3 cells. The current
      voltage relationship of INa was shifted to more negative potentials in the
      presence of this compound. Tef increased INa with an EC50 value of 3.2 +/- 0.8
      microM. It also increased the amplitude of persistent INa. Tef reduced the
      amplitude of L-type Ca2+ current. This agent slightly inhibited K+ outward
      current; however, it had no effect on the activity of large-conductance Ca2+
      activated K+ channels. Under cell-attached voltage-clamp recordings, Tef (10
      microM) increased amplitude and frequency of spontaneous action currents, along
      with appearance of oscillatory inward currents. Tef-induced inward currents were
      suppressed after further application of tetrodotoxin, riluzole or ranolazine. In
      GT1-7 cells, Tef also increased the amplitude and frequency of action currents.
      Taken together, the effects of Tef and its structural related pyrethroids on ion
      currents can contribute to the underlying mechanisms through which they affect
      endocrine or neuroendocrine function in vivo.

PMID- 19378471
TI  - The shoulds--and the shouldn'ts--of getting your shots.

PMID- 19378472
TI  - All the pretty pictures.  CT scans can speed a diagnosis and make it more
      accurate, but there's also cost and radiation to worry about.

PMID- 19378473
TI  - Weighing on our minds.  The abdominal fat we put on in middle age may wind up
      causing dementia when we're older.

PMID- 19378474
TI  - By the way, doctor. Within a three-month period, both my sister and her husband
      (both in their 40s) were hospitalized with pulmonary embolisms. Any thoughts on
      the cause? Could it be something in the air?

PMID- 19378475
TI  - Lifestyle prevention: does it work?  And why?

PMID- 19378476
TI  - Climate change and your health.

PMID- 19378477
TI  - Genetic screening for prostate cancer.

PMID- 19378478
TI  - On call.  I am 55 years old.  My cholesterol counts are normal, but my wife
      clipped a newspaper article about a study that found statin drugs prevent heart
      attacks even in people with normal cholesterol.  My golfing partners all take
      cholesterol medication-- should I join them?

PMID- 19378479
TI  - Monitoring the incidence and causes of diseases potentially transmitted by food
      in Australia: annual report of the OzFoodNet Network, 2007.
AB  - In 2007, OzFoodNet sites reported 27,332 notifications of 8 diseases or
      conditions that are commonly transmitted by food. The most frequently notified
      infections were Campylobacter (16,984 notifications) and Salmonella (9,484
      notifications). Public health authorities provided complete serotype and phage
      type information on 96% of all Salmonella infections in 2007. The most common
      Salmonella serotype notified in Australia during 2007 was Salmonella Typhimurium,
      and the most common phage type was Salmonella Typhimurium 135. During 2007,
      OzFoodNet sites reported 1,882 outbreaks of gastrointestinal illness; the
      majority of these were spread person to person but included those transmitted by
      contaminated food. In total, these outbreaks affected 37,474 people and resulted
      in 1,034 people being admitted to hospital. During these outbreaks there were 114
      deaths reported. Food was suspected or confirmed as the mode of transmission for
      149 of these outbreaks, which affected 2,290 persons, hospitalised 266 persons
      and 5 deaths were reported during these outbreaks. For these foodborne outbreaks,
      S. Typhimurium was the most common aetiological agent and restaurants were the
      most common setting where foods were prepared. Twenty-four of these foodborne
      outbreaks were related to the consumption of eggs; the majority (n = 22) of these
      outbreaks were due to various phage types of S. Typhimurium. This report
      summarises the incidence of disease potentially transmitted by food in Australia
      and details outbreaks associated with various food vehicles in 2007. These data
      assist agencies to identify emerging disease, develop food safety policies, and
      prevent foodborne illness.

PMID- 19378481
TI  - [Exercise, physical activities and public health (1) Exercise epidemiological
      study to meet the needs of society].

PMID- 19378480
TI  - [Patient information. Ischemic colitis].

PMID- 19378482
TI  - [The current status and future issues on anti-tuberculosis campaign in Japan (5)
      The status and problems related to molecular epidemiological studies on
      tuberculosis organisms].

PMID- 19378483
TI  - [Regional health in the 21st century (5) Public health administration in the
      United States, Germany and England].

PMID- 19378484
TI  - WHO Surgical Safety Checklist has value worldwide.

PMID- 19378485
TI  - Research vital to improve sexual health of refugees.

PMID- 19378486
TI  - Nanotechnology crucial in fighting infectious disease.

PMID- 19378487
TI  - [How do we deal with mild cognitive impairment?].

PMID- 19378488
TI  - [Is depression seen in the aged a risk factor for cognition disorder?].

PMID- 19378489
TI  - [Are there many patients with dementia with Lewy bodies in Japan?].

PMID- 19378490
TI  - The fate of Marmaduke Tunstall's collections.

PMID- 19378491
TI  - [The health worker shortage in Africa worse than supposed].

PMID- 19378492
TI  - J.W. Bennett's "Fishes of Ceylon," dates of publication from supplementary
      sources with notes on copies of the book, alleged original drawings, and the
      author's specimens.

PMID- 19378493
TI  - Retraction. The Fas/Fas ligand pathway and Bcl-2 regulate T cell responses to
      model self and foreign antigens.

PMID- 19378494
TI  - Sir James Edward Smith and the introduction of botany in Greece during the late
      eighteenth and early nineteenth centuries.

PMID- 19378495
TI  - Retraction. Autoimmunity as a consequence of retrovirus-mediated expression of C
      FLIP in lymphocytes.

PMID- 19378496
TI  - A review of some early testimony from the new world in respect of the great auk,
      "pinguinus impennis".

PMID- 19378497
TI  - [New groups of drugs for HIV infection therapy].

PMID- 19378498
TI  - An "uninteresting scrawl": some correspondence of Marmaduke Tunstall (1743-1790).

PMID- 19378499
TI  - [How long should drug therapy be continued for Alzheimer disease?].

PMID- 19378500
TI  - A note on the term "lichenologist" and its synonyms.

PMID- 19378501
TI  - [The institution of the "Buonuomini del Bigallo" and the subordination of the
      Florentine charitable organizations to the centralizing directive of the
      principate of Cosimo I de' Medici].

PMID- 19378502
TI  - [Problems of citizen provisioning and political measures of food provisioning in
      Florence during the 15th century (1430-1500)].

PMID- 19378503
TI  - [Drug therapy to treat behavioral and psychological symptoms of dementia--with
      special reference to anti-psychotic drugs].

PMID- 19378505
TI  - [Liaison psychotherapy in the management of cancer].

PMID- 19378504
TI  - Trisomy 12p and monosomy 4p: phenotype-genotype correlation.
AB  - 4p Monosomy and 12p trisomy have been discussed and redefined along with recently
      reviewed chromosomal syndromes. 12p Trisomy syndrome is characterized by normal
      or increased birth weight, developmental delay with early hypotonia, psychomotor
      delay, and typical facial appearance. Most likely, the observed phenotypic
      variability depends on the type and extent of the associated partial monosomy.
      Partial deletions of the short arm of one chromosome 4 cause the Wolf-Hirschhorn
      syndrome (WHS). Affected patients present Greek helmet face, growth and mental
      retardation, hypotonia, and seizures. The combination of these characteristics
      constitutes the phenotypic core of WHS. We present a clinical and molecular
      cytogenetic characterization of a 4-year old mentally retarded girl with
      macrosomy, facial dysmorphisms, and epilepsy, in whom an unbalanced
      t(4;12)(p16.3;p13.3) translocation was detected, giving rise to partial 4p
      monosomy and partial 12p trisomy. Because the patient shows most of the
      phenotypic characteristics of 12p trisomy, this case could contribute to a better
      definition of the duplicate critical region that determines the phenotype of the
      12p trisomy syndrome.

PMID- 19378506
TI  - A duplex allele-specific amplification PCR to detect SMN1 deletion.
AB  - Spinal muscular atrophy (SMA), the leading genetic cause of death in childhood,
      is an autosomal recessive neuromuscular disorder characterized by progressive
      muscle weakness, associated with deletions of the survival motor neuron (SMN)
      gene identified and mapped to chromosome 5q13. SMN is present in two highly
      homologous copies (SMN1 and SMN2). In the general population, normal individuals
      (noncarriers) have at least one telomeric (SMN1) copy, and 5% of them have no
      copies of SMN2. Approximately 95% of SMA patients carry homologous deletions of
      SMN1 exon(s) 7 (and 8). SMN1 and SMN2 exons 7 and 8 differ only by 1 bp each, and
      SMA diagnosis might be performed by single-strand conformational polymorphism,
      PCR amplification followed by restriction fragment length polymorphism (RFLP),
      multiple ligation-dependent probe amplification, or realtime PCR of SMNs exons 7
      and 8. We developed a simpler and cost-effective method to detect SMN1 exon 7
      deletion based on allele-specific amplification PCR.

PMID- 19378507
TI  - [Drug therapy intended for cancer patients].

PMID- 19378508
TI  - [Psychotherapy directed to cancer patients].

PMID- 19378509
TI  - [Dignity of cancer patients].

PMID- 19378510
TI  - [Current topics on dementia].

PMID- 19378511
TI  - [Higher nervous activity tests for dementia].

PMID- 19378512
TI  - [Automobile driving by dementia patients: a need for social support].

PMID- 19378513
TI  - [Diagnosis and treatment of dementia].

PMID- 19378514
TI  - Continuous infusion of remifentanil versus sufentanil in videolaparoscopic
      surgeries. A comparative study.
AB  - BACKGROUND AND OBJECTIVES: Continuous infusion (CI) of remifentanil is common in
      total intravenous anesthesia. On the other hand, CI of sufentanil for
      short/medium-term surgeries has not been widely used. The objective of this study
      was to compare two techniques of total intravenous anesthesia, using CI of
      remifentanil or sufentanil, regarding their intraoperative behavior and
      characteristics of recovery of patients undergoing videolaparoscopic surgeries.
      METHODS: Sixty patients, equally divided in 2 groups (RG, and SG), participated
      in this study. Continuous infusion of remifentanil was used for anesthetic
      induction in RG, while a bolus of sufentanil associated with CI of this drug was
      used in SG. The CI of remifentanil was discontinued at the end of the surgery,
      while the CI of sufentanil was discontinued 20 minutes before the end of the
      surgery. Patients received ketoprofen and dypirone intraoperatively. Tramadol was
      used for rescue analgesia in the recovery room. Variations of mean arterial
      pressure (MAP) and hard reate (HR), time for awakening, propofol consumption,
      intercurrences in the recovery room, and time of stay in the recovery room were
      analyzed. RESULTS: Mean MAP was greater in SG than in RG (91.9 x 77.6, p <
      0.0001). The incidence of pain was significantly greater in RG than on SG (22 x 1
      patient, p < 0.0001). The incidence of postoperative nausea and vomiting (PONV)
      was greater in RG than in SG (10 x 2 patients, p < 0.0098). The mean time of stay
      in the recovery room was greater in RG than in SG (76 x 49 min, p < 0.0001).
      CONCLUSIONS: Hemodynamic control was satisfactory in both groups. Continuous
      infusion of sufentanil promoted better postoperative pain control with decreased
      consumption of rescue analgesic and, consequently, reduced incidence of PONV and
      reduced time of stay in the recovery room.

PMID- 19378515
TI  - A comparative study between one and two effective doses (ED95) of rocuronium for
      tracheal intubation.
AB  - BACKGROUND AND OBJECTIVES: Neuromuscular blockers (NMB) are used to induce
      relaxation of skeletal muscles and facilitate tracheal intubation (TI). According
      to the literature, two effective doses (ED95) of NMB are ideal for TI. Rocuronium
      is a steroid-type, synthetic, non-depolarizing neuromuscular blocker of medium
      duration. The objective of this study was to evaluate and compare the conditions
      of tracheal intubation with one and two effective doses (ED95) of rocuronium,
      following the criteria of the Copenhagen Consensus Conference. METHODS: Sixty
      patients of both genders, ages 20 to 60 years, physical status ASA I and II,
      Mallampati 1 and 2, body mass index (BMI) < 35, who underwent general anesthesia,
      randomly divided in two groups of 30 patients, were evaluated. Group 1 (G1)
      received 0.3 mg kg(-1) of rocuronium (1 ED95, and Group 2 (G2) received 0.6 mg
      kg(-1) (2 DE95). Parameters used to evaluate TI were based on the criteria of the
      Copenhagen Consensus Conference (Good Clinical Research Practice): laryngoscopy,
      vocal cords (position and movements), reaction to the insertion of the tube
      and/or filling of the cuff (movements of limbs and cough). RESULTS: All
      intubations were considered excellent or good (acceptable); therefore, there were
      no cases of failure or any intubation considered bad (unacceptable). The results
      of the statistical analysis were not significant. Consequently, we did not
      observe any clinically significant differences in the parameters evaluated
      CONCLUSIONS: Both doses of rocuronium, 0.3 mg kg(-1) and 0.6 mg kg(-1) ED95,
      provided clinically satisfactory parameters of TI in elective procedures.

PMID- 19378516
TI  - Patients with sequelae of poliomyelitis. Does the anesthetic technique impose
      risks?
AB  - BACKGROUND AND OBJECTIVES: Several questions arise before performing neuro-axis
      block in patients with sequelae of poliomyelitis. Reports in the literature are
      scarce. The objective of this study was to describe the anesthetic techniques
      used in patients undergoing surgeries and possible complications. METHODS: We
      undertook a retrospective study of patients with sequelae of poliomyelitis who
      underwent surgeries during a five-year period. Demographic data, physical status
      (ASA), onset of the disease, body part affected, diagnosis of post-poliomyelitis
      syndrome, surgeries and type anesthesia used, postoperative analgesia, intra- and
      postoperative complications, outpatient follow-up, and development of
      neurological changes were evaluated. RESULTS: One-hundred and twenty-three
      patients who underwent 162 surgical procedures were evaluated. Most patients (n =
      82; 66.6%) had neurological sequela in a lower limb. Patients developed acute
      poliomyelitis at approximately 28 months of age. Orthopedic surgery was performed
      in 87.7% of patients. Neuro-axis block was used in 64.1% of the cases; epidural
      block was more frequent. Intraoperative complications reported included:
      accidental puncture of the dura-mater (n = 1; 0.61%), bradycardia (n = 1; 0.61%),
      hypotension (n = 2; 1.23%), and apnea and thoracic rigidity (n = 1; 0.61%).
      Postoperative complications included: vomiting (n = 2; 1.23%), urinary retention
      (n = 4; 2.64%), and complex regional pain syndrome type 1 (n = 2; 1.23%).
      Patients were followed for 22 months and worsening of the neurological disorder
      was not observed. CONCLUSIONS: Patients with sequelae of poliomyelitis who
      underwent neuro-axis block did not develop any postoperative complications or
      worsening of their neurological status that could be attributed to the anesthetic
      technique used.

PMID- 19378517
TI  - The intraoperative use of warming blankets in patients undergoing radical
      prostatectomy is related with a reduction in post-anesthetic recovery time.
AB  - BACKGROUND AND OBJECTIVES: Anesthesia and the surgeries cause substantial thermal
      changes, and hypothermia can lead to cardiovascular complications, clotting
      disorders, immunologic changes, and disruption of water and electrolyte balances,
      besides decreasing drug metabolism and, therefore, increasing post-anesthetic
      recovery time (PART). Circulation of warm air (forced-air warming blanket) is the
      most effective non-invasive warming method currently available. The objective of
      the present study was to compare the time spent in the recovery room of patients
      undergoing radical prostatectomy with and without the intraoperative use of a
      forced-air warming blanket. METHODS: Male patients between 45 and 75 years, ASA
      PS I, II, and III undergoing radical prostatectomy under general anesthesia
      during 2004 were studied. Data gathered included: age, weight, physical status,
      anesthetic technique, use of warming blanket, and time spent in the recovery
      room. The data was recorded on an Excel chart and analyzed by the Mann-Whitney
      test. RESULTS: Patients in whom the warming blanket was used intraoperatively
      remained a mean of 139.66 +/- 58.6 minutes in the recovery room, while patients
      without the warming blanket spent a mean of 208.28 +/- 65.8 minutes in the
      recovery room (p < 0.0001). CONCLUSIONS: We concluded that the intraoperative use
      of the warming blanket in patients undergoing radical prostatectomy was
      associated with a significant reduction in the time patients spent in the
      recovery room.

PMID- 19378518
TI  - Breakage of epidural catheters: etiology, prevention, and management.
AB  - BACKGROUND AND OBJECTIVES: The objective of this study was to review published
      cases of breakage of epidural catheters and, with the data gathered in the
      literature, to identify predisposing factors for catheter breakage, and list the
      recommended conducts to prevent and treat this complication. METHODS: The search
      included the data banks of Pubmed, Embase, and SciELO. RESULTS: A total of
      fifteen studies reporting 30 cases of breakage of epidural catheters were
      identified. Information regarding the catheterization and removal of the
      catheter, besides the type of catheter, were analyzed for each case.
      Complications related to the presence of retained catheter fragments, as well as
      the indications for exploratory laminectomy, were recorded. With the evidence
      gathered from the literature, recommendations for prophylaxis and treatment of
      this complication were elaborated. CONCLUSIONS: The catheter should not be
      inserted more than five centimeters into de epidural space. Exploratory
      laminectomy should be undertaken if the patient develops signs or symptoms of
      neurologic changes, if the catheter is inside the subarachnoid space, or whenever
      the tip of the catheter is emerging out of the skin. Due to the difficulty to
      localize retained fragments by imaging exams, catheters should be manufactured
      with materials that improve their visualization.

PMID- 19378519
TI  - Comparison of histologic spinal cord and neurologic changes in guinea pigs after
      subarachnoid block with large volumes of racemic bupivacaine, 50% enantiomeric
      excess bupivacaine (S75-R25), and levobupivacaine.
AB  - BACKGROUND AND OBJECTIVES: Levobupivacaine has less central nervous system side
      effects than racemic bupivacaine, but its anesthetic effect is not as intense.
      The objective of this experimental study was to compare the adverse effects of
      large volumes of bupivacaine, S75-R25 bupivacaine, and levobupivacaine injected
      in the subarachnoid space of guinea pigs. METHODS: Forty guinea pigs were divided
      in four groups. They were anesthetized with 100% O2 and 2% isoflurane, followed
      by puncture of the L6-S1 intervertebral space. In Group 1, 2 mL of normal saline
      were injected; in Group II, 2 mL of 0.5% bupivacaine; in Group III, 2 mL of 0.5%
      S75-R25 bupivacaine, and in Group IV, 2 mL of 0.5% levobupivacaine. After the
      animal awakened, neurological exam was done at 0, 60, 120, and 180 minutes, and
      daily for one week. Animals were killed and underwent perfusion with 4%
      paraformaldehyde. After fixation, the spinal cord was isolated by dissection and
      analyzed histologically to evaluate the degree of spinal cord lesions. RESULTS:
      Guinea pigs in the control group did not present nervous block. Those in Group II
      presented sensitive and motor block for more than 180 minutes. Animals in Groups
      III (S75-R25) and IV (levobupivacaine) developed sensitive and motor blockade at
      moment 0, but at 60 minutes the motor blockade was minimal. Histologic exam in
      Group I showed no changes. In Group II, severe spinal cord changes were observed.
      In Groups III and IV, spinal cord changes were mild. CONCLUSIONS: Large volumes
      of levobupivacaine caused little damage in the central nervous system when
      compared with bupivacaine. Statistically significant changes were not observed
      between levobupivacaine and S75-R25 bupivacaine.

PMID- 19378520
TI  - Anesthesia for Blalock-Taussig shunt and pacemaker placement in an adult patient
      with univentricular heart. Case report.
AB  - BACKGROUND AND OBJECTIVES: Univentricular heart is a complex, rare, and severe
      cardiopathy, with no possibility of curative surgical treatment, associated with
      a high mortality in the first years of life. The objective of this article was to
      describe a rare case of an adult patient with uncorrected single ventricle who
      was admitted for pulmonary valvuloplasty but was submitted to a modified Blalock
      Taussig and placement of an epicardic pacemaker. The complementary objective of
      this report was to address the anesthetic particularities of adult patients with
      uncorrected congenital cardiopathy. CASE REPORT A 34 years old female patient,
      weighing 60 kg, with a complex congenital cardiopathy with a single ventricle,
      important infundibular pulmonary stenosis and moderate pulmonary hypertension was
      admitted to the hospital without conditions to undergo surgical correction. The
      patient had a history several therapeutic bleedings to treat polycythemia. She
      was admitted due to worsening hypoxemia, an episode of syncope, and recent onset
      of third degree atrioventricular block. On admission, the patient was
      hemodynamically stable, heart rate of 42 bpm, SpO2 73%, central cyanosis and
      cyanosis of the extremities, and blood pressure 120 x 70 mmHg. Cardiac
      catheterization and pulmonary valvuloplasty were proposed. Due to the
      impossibility of success of this technique, Blalock-Taussig procedure with
      placement of a pacemaker was indicated. The procedure was performed in the
      following day without intercurrences, and the patient was discharged 7 days after
      the surgery, with SpO2 85%, hematocrit 49%, and improvement of the dyspnea.
      CONCLUSIONS: The success of anesthesia for surgical correction of complex
      congenital cardiopathy requires knowledge on the pathophysiology of the disorder,
      as well as the particularities inherent to the anesthetic technique used.

PMID- 19378521
TI  - Painful peripheral polyneuropathy after bariatric surgery. Case reports.
AB  - BACKGROUND AND OBJECTIVES: The number of patients undergoing bariatric surgery
      increases every year and the frequency of complications associated with this
      procedure has been increasing. The main complications reported are nutritional,
      metabolic, neurological, and psychological/psychiatric. Among the neurological
      complications, peripheral neuropathies are important due to their high incidence.
      The objective of this report was to stress the importance of this type of
      complication, in which the initial manifestation might be neuropathic pain
      followed or accompanied by motor involvement, and whose prognosis depends on
      early diagnosis and treatment. CASE REPORTS: The case of three patients were
      reported, two females and one male, who underwent bariatric surgery (restrictive
      method - Roux-en-Y gastric bypass) and developed, postoperatively, peripheral
      neuropathy with neuropathic pain as the initial symptom, with posterior or
      concomitant motor involvement. Electroneuromyography demonstrated in all three
      cases a sensitive-motor axonal peripheral neuropathy. In two patients, the
      fibular nerves were severely affected. In common, they all had an important
      weight loss in a short period of time before developing neurological symptoms.
      CONCLUSIONS: Neurological complications are one of the most feared complications
      of bariatric surgeries. Nutritional deficiencies secondary to the surgery are the
      most important factors in its pathogeny. Nutritional surveillance, avoidance of
      severe and fast weight loss, and nutritional supplements are fundamental to avoid
      complications, especially neurological complications.

PMID- 19378522
TI  - Critical reading of the statistical data in scientific studies.
AB  - BACKGROUND AND OBJECTIVES: Statistics are a valuable tool that validates the
      conclusions of scientific works. The objective of this review was to present some
      concepts related to statistic calculations that are fundamental for the critical
      reading and analysis of medical literature. CONTENTS: In general, authors present
      the results of their studies as charts, boxes, and tables with quantitative data,
      along with descriptive statistics (means, standard deviations, medians), and
      almost always mention the statistic tests used. After reviewing several studies,
      it was difficult to find the value attributed to the statistical test. Thus, it
      is up to the reader to evaluate the adequacy of the information, and to search
      for evidence that contradict possible mistakes that could threaten the validity
      of their conclusion. CONCLUSIONS: Examining the design of the studies one
      observes that, in many of them, excessive importance is given to statistical
      calculations as definitive factors, irrefutable evidence of arguable, or
      equivocal, conclusions.

PMID- 19378523
TI  - Cannabinoids in chronic pain and palliative care.
AB  - BACKGROUND AND OBJECTIVES: Several studies have focused on Cannabis sativa (Cs)
      due to its analgesic potential and its ability to alleviate symptoms of disorders
      of the central nervous system. However, since marijuana, one of its popular
      names, is the most common illicit drug throughout the world, it breeds prejudice
      both among lay people and health care professionals. The objective of this study
      was to determine the current level of knowledge about this drug and the
      perspectives for its use, to better understand its actions and effects, both in
      experimental studies and clinical use, in patients with degenerative neurological
      disorders or in those who do not have the possibility of cure and are being
      followed by palliative care programs. CONTENTS: The therapeutic use of Cannabis
      sativa is not recent. The present study presents the historical background and
      pharmacology of Cs, the development of its therapeutic use through synthetic
      cannabinoids, the current scientific knowledge, and its organic and psychological
      consequences, demonstrating the options for its clinical use and future
      perspectives. CONCLUSIONS: Pure delta-9-tetrahydrocannabinol (Delta9-THC) and its
      analogues have clinical applicability, being beneficial in selected individuals.
      The development of pure synthetic substances, in an attempt to attenuate
      undesirable psychoactive effects, indicates that perspectives for its use in the
      future are favorable. More detailed studies should be undertaken. Ample debates
      will be necessary to create standards for its formulation and clinical
      availability, since it is a substance that generates prejudice, due to its
      illegal commercialization and use, and also because its use has been attributed
      to mysticism.

PMID- 19378524
TI  - Mechanisms of analgesia of intravenous lidocaine.
AB  - BACKGROUND AND OBJECTIVES: Intravenous lidocaine has been used for several
      indications since the decade of 1960. Its multimodal mechanism of action was the
      objective of this review. CONTENTS: Mechanisms of action that diverge from the
      classical Na+ channel blockade, the differential action of intravenous lidocaine
      in central sensitization, and the analgesic and cytoprotective actions, as well
      as the different doses of intravenous lidocaine were reviewed. CONCLUSIONS: The
      final analgesic action of intravenous lidocaine is a reflection of its
      multifactorial action. It has been suggested that its central sensitization is
      secondary to a peripheral anti-hyperalgic action on somatic pain and central on
      neuropathic pain, which result on the blockade of central hyperexcitability. The
      intravenous dose should not exceed the toxic plasma concentration of 5 microg mL(
      1); doses smaller than 5 mg kg(-1), administered slowly (30 minutes), under
      monitoring, are considered safe.

PMID- 19378525
TI  - Depression in patients with advanced cancer and pain.
AB  - BACKGROUND AND OBJECTIVES: The importance of emotional symptoms in the context of
      the health-disease binomium, and efforts to spread information on Palliative
      Medicine motivated this article. The objective of this literature review was to
      propose a reflection on the diagnosis of depression in patients with advanced
      cancer with pain, based on existing concepts and definitions. CONTENTS: Pain and
      depression are prevalent symptoms in cancer patients. Considering the different
      points of intersection between physical and mental diseases, sometimes the
      diagnosis of depression in patients with cancer and pain is difficult. This datum
      is very important because depression decreases considerably the quality of life
      of patients, and should be diagnosed and treated properly CONCLUSIONS: After
      reviewing the literature, a few questions remained unanswered. This fact awakens
      the interest to undertake studies that propose precise diagnostic solutions and
      efficient treatment of this symptom in patients with advanced cancer.

PMID- 19378526
TI  - Intravenous regional anesthesia--first century (1908-2008). Beggining,
      development, and current status.
AB  - BACKGROUND AND OBJECTIVES: Intravenous regional block is celebrating its 10th
      anniversary in 2008. Since this is a widely used technique, this milestone should
      be recorded, the date celebrated, Brazilian anesthesiologists should be
      remembered of its evolutive process, especially in the last 40 years, and we
      should pay homage to the individual who started it: August Karl Gustav Bier.
      CONTENTS: This report describes the beginning of locoregional anesthesia in
      general and regional intravenous block in particular, since the introduction of
      garroting of the extremities to the discovery and improvement of needles,
      syringes, and local anesthetics. The technical details used initially by Bier,
      and the pathophysiological and clinical concepts enounced by him at the beginning
      of the 20th Century are described. It describes the initial evolution and that of
      the following decades of intravenous regional block, lists national and
      international pioneers, explains the reasons for the relatively late scientific
      studies on the technique, and describes the main contributions that made it an
      effective and safe technique. Finally, it describes the current state of the main
      knowledge acquired over the years, such as the mechanism and site of action of
      the anesthetic and ischemia, the use of modern anesthetic solutions, improvement
      of postoperative analgesia and motor block, pharmacokinetic and
      pathophysiological concepts, and the best interpretation of possible
      complications. CONCLUSIONS: Intravenous regional block is the anesthetic
      technique created by A. K. G Bier exactly 100 years ago. In the first half of the
      20th Centuty, it evolved little and slowly, but in the last several years, it has
      seen an accentuated improvement, thanks to countless technical,
      pathophysiological, pharmacological, pharmacokinetic, and clinical developments,
      for which Brazilian Anesthesiology has contributed considerably. Since it is
      celebrating its 100th anniversary in 2008, intravenous regional block deserves to
      have its story told, and the date should not go unnoticed, but should be
      remembered and celebrated.

PMID- 19378527
TI  - Ethics committee, conflict of interest, and registry of clinical assays.

PMID- 19378528
TI  - Effects of pudendal nerve, epidural and subarachnoid block on coagulation of
      pregnant women.
AB  - BACKGROUND AND OBJECTIVES: The significant reduction in postoperative
      thromboembolic complications has been attributed to the use of regional block,
      probably due to attenuation of the neuroendocrine-metabolic response. Pregnant
      women, who demonstrate important hypercoagulability, can in theory benefit from
      this effect during labor. The objective of this study was to determine the
      effects of regional block on coagulation of pregnant women. METHODS: Thirty
      patients in the 3rd trimester were enrolled; ten patients underwent epidural
      block for cesarean section with 150 mg of 0.5% bupivacaine without epinephrine
      and 2 mg of morphine (PD group); ten underwent subarachnoid block for cesarean
      section with 15 mg of 0.5% hyperbaric bupivacaine and 0.2 mg of morphine (SA
      group); and ten, pudendal block for vaginal delivery with up to 100 mg of 0.5%
      bupivacaine without epinephrine (BP group). Coagulation tests (prothrombin time,
      thrombin time, activated partial thromboplastin time) and thromboelastography (r
      time, k-time, r+k-time, alpha-angle, maximum amplitude) were performed in the
      following moments: before and after the blockade, after delivery, and 24 hours
      after the blockade in PD and SA groups. In the BP group, the evaluation was done
      before the blockade, after delivery, and 24 hours after the blockade. RESULTS:
      The results indicate that the anesthetic technique did not influence coagulation
      of pregnant women. They also demonstrate that coagulation is activated during
      labor, which is responsible for the changes seen in all the study groups.
      CONCLUSIONS: In the conditions of the present study, the sympathetic blockade and
      the local anesthetic did not have any influence on the coagulation of pregnant
      women at term undergoing epidural, subarachnoid, or pudendal nerve block.

PMID- 19378529
TI  - Simulation of ultrasound-guided peripheral nerve block: learning curve of CET
      SMA/HSL Anesthesiology residents.
AB  - BACKGROUND AND OBJECTIVES: The use of ultrasound imaging in peripheral nerve
      block has been increasing. However, there are few reports in the literature on
      the learning curve of the ultrasound technique. The objective of this report was
      to evaluate the learning curve of CET-SMA/HSL Anesthesiology residents of
      ultrasound-guided peripheral block using an experimental agar model. METHODS: An
      experimental model was developed by filling a bowl with agar and olives. Nine
      residents were randomly divided in three groups (G1, G2, and G3), each one with a
      R1, a R2, and a R3. All three groups received theoretical explanation. G1 also
      had two hours of practical training, G2 had one hour, and G3 had no training.
      Residents were then asked to place a needle at the middle of the olive wall, near
      the transducer and then reposition the needle between the olive and the bottom of
      the bowl, simulating the epidural injection of anesthetic. The speed and efficacy
      of the tasks, as well as technical flaws, were evaluated. RESULTS: The mean
      length of time to perform the tasks was 37.63 seconds for G1, without technical
      flaws; 64.40 seconds for G2, with two technical flaws; and 93.83 seconds for G3,
      with 12 technical flaws. CONCLUSIONS: This study allows us to conclude that the
      longer training of ultrasound-guided peripheral nerve block in an experimental
      model improved the learning curve of the technique.

PMID- 19378530
TI  - Hemodynamic impact of alveolar recruitment maneuver in patients evolving with
      cardiogenic shock in the immediate postoperative period of myocardial
      revascularization.
AB  - BACKGROUND AND OBJECTIVES: Alveolar recruitment maneuver (ARM) with pressures of
      40 cmH2O in the airways is effective in the reversal of atelectasis after
      myocardial revascularization (MR); however, there is a lack of studies evaluating
      the hemodynamic impact of this maneuver in patients who evolve with cardiogenic
      shock after MR. The objective of this study was to test the hemodynamic tolerance
      to ARM in patients who develop cardiogenic shock after MR. METHODS: Ten hypoxemic
      patients in cardiogenic shock after MR were evaluated after admission to the ICU
      and hemodynamic stabilization. Ventilatory adjustments included tidal volume of 8
      mL x kg(-1), PEEP 5 cmH2O, RR 12, and FiO2 0.6. Continuous pressure of 40 cmH2O
      was applied to the airways for 40 seconds in three cycles. Between cycles,
      patients were ventilated for 30 seconds, and after the last cycle, PEEP was set
      at 10 cmH2O. Hemodynamic measurements were obtained 1, 10, 30, and 60 minutes
      after ARM, and arterial and venous blood samples were drawn 10 and 60 minutes
      after the maneuver to determine lactate levels and blood gases. ANOVA and the
      Friedman test were used to analyze the data. A p of 0.05 was considered
      significant. RESULTS: Alveolar recruitment maneuver increased the ratio PaO2/
      FiO2 from 87 to 129.5 after 10 minutes and to 120 after 60 minutes (p < 0.05) and
      reduced pulmonary shunting from 30% to 20% (p < 0.05). Hemodynamic changes or
      changes in oxygen transport immediately after or up to 60 minutes after the
      maneuver were not detected. CONCLUSIONS: In patients who evolved to cardiogenic
      shock and hypoxemia after MR, ARM improved oxygenation and was well tolerated
      hemodynamically.

PMID- 19378531
TI  - Hypoxemia after myocardial revascularization: analysis of risk factors.
AB  - BACKGROUND AND OBJECTIVES: Severe hypoxemia is complication frequently seen in
      the immediate postoperative period of myocardial revascularization (MR),
      increasing the duration of mechanical ventilation, the incidence of pulmonary
      infections, hospital costs, and mortality. The objective of this study was to
      identify predictive factors of severe hypoxemia in patients undergoing MR.
      METHODS: Four-hundred and eighty-one adult patients undergoing elective MR
      between October 2003 and March 2004 were enrolled in this study. Severe hypoxemia
      was defined as PaO2/FiO2 < 150 upon admission to the ICU. The Chi-square test,
      Student's t or Wilcoxon test, followed by multivariate analysis and logistic
      regression (LR) for parameters with p < 0.25 in the univariate analysis, were
      used for the statistical analysis. A p > 0.2 was required to exclude the
      parameter from the LR model, and a p < 0.1 was considered significant. RESULTS:
      Time for extubation was greater in patients with severe hypoxemia (p < 0.001).
      Multivariate analysis identified age (p = 0.081), weight (p = 0.001), need of
      prolonged CBP (p = 0.033), and left ventricular dysfunction (p = 0.082) as
      independent predictors of severe hypoxemia. CONCLUSIONS: Older and overweighted
      patients, those with left ventricular dysfunction, and those who needed CPB
      presented an increased risk of severe hypoxemia after MR. In those patients, the
      use of perioperative ventilatory strategies, with elevated positive expiratory
      pressures and alveolar recruitment maneuver should be considered to prevent
      postoperative pulmonary dysfunction.

PMID- 19378532
TI  - In vitro and in vivo neuromuscular effects of atracurium and rocuronium in rats
      treated with carbamazepine for seven days.
AB  - BACKGROUND AND OBJECTIVES: This experimental study investigated the in vitro and
      in vivo neuromuscular blockade of rocuronium and atracurium in rats treated with
      carbamazepine and determined the concentration of cytochrome P450 and b5
      reductase in hepatic microsomes. METHODS: Rats were treated with carbamazepine
      (CBZ)--40 mg x kg(-1) by gavage and sacrificed on the eighth day under anesthesia
      with urethane. In vitro and in vivo preparations followed the techniques of
      Bulbring and Leeuwin and Wolters, respectively. Concentrations and doses of the
      neuromuscular blockers used in in vitro and in vivo preparations were,
      respectively, 20 microg x mL(-1) and 0.5 mg x kg(-1) for atracurium (ATC); and 4
      microg x kg(-1) and 0.6 mg x kg(-1) for rocuronium (ROC). Each protocol had an n
      = 5 and the response was observed for 60 minutes. The effects of ATC and ROC were
      evaluated in the preparations of rats treated with carbamazepine (CBZ(t)) and
      compared to those of non-treated rats (CBZ(st)). The concentration of cytochrome
      P450 and b5 reductase were determined in hepatic chromosomes of rats treated with
      carbamazepine (CBZ(t)) and non-treated rats (CBZ(st)). RESULTS: Carbamazepine did
      not change the amplitude of neuromuscular response; differences in the
      neuromuscular blockade produced by atracurium in CBZ1 preparations were not
      observed, in vitro or in vivo, when compared with CBZ(st); the neuromuscular
      blockade produced by rocuronium in CBZ(t) preparations was potentiated in vitro.
      Carbamazepine did not change the concentrations of cytochrome P450 and b5.
      CONCLUSIONS: Seven-day treatment with carbamazepine did not change the
      neuromuscular blockade produce by atracurium, but altered the in vitro effects of
      rocuronium. The duration of the treatment was not enough to cause enzymatic
      induction and decrease the sensitivity to rocuronium.

PMID- 19378533
TI  - Phrenic nerve block after interscalene brachial plexus block. Case report.
AB  - BACKGROUND AND OBJECTIVES: Phrenic nerve block is a common adverse event of
      brachial plexus block. However, in most cases it does not have any important
      clinical repercussion. The objective of this work was to report a case with
      phrenic nerve block with respiratory repercussions in a patient with chronic
      renal failure who had an extensive arteriovenous fistula created under
      perivascular interscalene brachial plexus block. CASE REPORT: A 50-year old male
      patient, smoker, with chronic renal failure on hemodialysis, hypertension,
      hepatitis C, diabetes mellitus, and chronic obstructive pulmonary disease, was
      scheduled for creation of an arteriovenous fistula in the right upper limb under
      interscalene brachial plexus block. The brachial plexus was identified by a
      peripheral nerve stimulator. Thirty-five milliliter of a local anesthetic mixture
      containing equal parts of 2% lidocaine with epinephrine at 1:200.000 and 0.75%
      ropivacaine were injected. After the injection, the patient was alert and
      oriented, but developed dyspnea and predominance of intercostal respiration on
      the side of the blockade. Breath sounds were not present in the right base. SpO2
      was maintained at 95% with oxygen through nasal cannula. Institution of invasive
      ventilatory support was not necessary. A chest X-ray showed the right
      hemidiaphragm on the 5th intecostal space. The patient returned to normal after
      three hours. CONCLUSION: In this case, the patient developed complete paralysis
      of the phrenic nerve with respiratory symptoms. Although invasive treatment was
      not necessary, it is necessary to alert anesthesiologists to restrict the
      indication of this technique.

PMID- 19378534
TI  - Accidental subarachnoid administration of 4 mg of morphine. Case report.
AB  - BACKGROUND AND OBJECTIVES: The subarachnoid administration of morphine is a well
      established anesthetic technique of postoperative analgesia due to its efficacy
      safety and low cost. The objective of this paper was to report the accidental
      subarachnoid administration of 4 mg of morphine complicated by atrial
      fibrillation after administration of naloxone. CASE REPORT: A 45-year old male
      patient with 75 kg, 1.72 m, physical status ASA II, hypertensive, was scheduled
      for reconstruction of the anterior cruciate ligament of the left knee. After
      spinal anesthesia, it was noticed that the vial of morphine had been changed
      resulting in the accidental subarachnoid administration of 4 mg of morphine (0.4
      mL of the 10 mg vial). Respiratory rate varied from 12 to 16 bpm and the patient
      remained hemodynamically stable without intraoperative complaints. Thirty minutes
      after admission to the post-anesthesia recovery unit the patient developed
      vomiting and diaphoresis being treated with 0.4 mg of naloxone followed by
      continuous infusion of 0.2 mg x (-1) until the symptoms had subsided. Continuous
      naloxone infusion was maintained in the Intensive Care Unit (ICU), where blood
      pressure, heart rate, respiratory rate and oxygen saturation were monitored as
      well as the presence of nausea, pruritus, vomiting, sedation, pain and urinary
      retention. Two hours after arriving at the ICU the patient developed acute atrial
      fibrillation without hemodynamic instability. Sinus rhythm was reestablished
      after the administration of 150 mg of amiodarone and discontinuation of the
      naloxone infusion. During the following 18 hours the patient remained
      hemodynamically stable and did not experience any other intercurrence until his
      discharge from the hospital. CONCLUSIONS: The present report is an alert for the
      risk of inadvertently switching of drugs during anesthesia, stressing the
      importance of referring patients being treated for opiate overdose to the ICU,
      due to the potential adverse reactions.

PMID- 19378535
TI  - Acute pulmonary edema associated with obstruction of the airways. Case report.
AB  - BACKGROUND AND OBJECTIVES: Negative pressure pulmonary edema has been defined as
      non-cardiogenic edema, with transudation of fluid to the interstitial space of
      the lungs due to an increase in negative intrathoracic pressure secondary to
      obstruction of the upper airways. This is the case of a healthy patient who
      underwent general anesthesia and developed acute pulmonary edema after
      extubation. CASE REPORT: A 23-year old female patient, physical status ASA II,
      underwent gynecologic videolaparoscopy under general anesthesia. The procedure
      lasted 3 hours without intercurrence. After extubation the patient developed
      laryngeal spasm and reduction in oxygen saturation. The patient improved after
      placement of an oral cannula and administration of oxygen under positive pressure
      with a face mask. Once the patient was stable she was transferred to the recovery
      room where, shortly after her arrival, she developed acute pulmonary edema with
      elimination of bloody serous secretion. Treatment consisted of elevation of the
      head, administration of oxygen via a face mask, furosemide and fluid restriction.
      Chest X-ray was compatible with acute pulmonary edema and normal cardiac area.
      Electrocardiogram (ECG), echocardiogram and cardiac enzymes were normal. The
      condition of the patient improved and she was discharged from the hospital the
      following day, asymptomatic. CONCLUSIONS: Acute pulmonary edema associated with
      obstruction of the upper airways can aggravate surgical procedures with low
      morbidity, affecting mainly young patients. Early treatment should be instituted
      because it has a fast evolution and, in most cases, resolves without lasting
      damages.

PMID- 19378536
TI  - Anesthesia in a patient with multiple endocrine abnormalities. Case report.
AB  - BACKGROUND AND OBJECTIVES: Insulinoma is the most common pancreatic endocrine
      tumor and it can be associated with multiple endocrine neoplasia (MEN). This is a
      report on a patient with multiple endocrine abnormalities, who did not fulfill
      the criteria of known syndromes (MEN) and the clinical-anesthetic particularities
      that influenced the anesthetic management. CASE REPORT A 23-year old female
      patient with episodes of hypoglycemia difficult to control, associated with
      Cushing's disease and prolactinoma without symptoms of pituitary compression and
      with normal thyroid and parathyroid. Investigation found a retroperitoneal mass
      of unknown origin which in face of the clinical presentation raised the
      hypothesis of insulinoma. The patient also referred to be a Jehovah's Witness.
      Biopsy of the mass by video-laparoscopy and enucleation of the insulinoma were
      proposed. On physical exam the patient was overweight, had protruding teeth, she
      was classified as Mallampati 3 and had symptoms of sleep apnea. Laboratorial
      exams revealed hematocrit 58%. Pre-anesthetic medication consisted of oral
      midazolam (7.5 mg) and clonidine (200 microg). Fentanyl (150 microg), clonidine
      (90 microg), propofol (150 mg) and pancuronium (8 mg) were used for anesthetic
      induction and she was intubated without intercurrences. Central venous access and
      invasive blood monitoring were instituted. Intravenous infusion of D5W with
      electrolytes was instituted and capillary glucose levels were monitored every 30
      minutes, which did not demonstrate any episodes of hypoglycemia during the
      surgery. The patient remained hemodynamically stable even during the
      pneumoperitoneum. She developed postoperative episodes of hypoglycemia, which
      motivated the re-operation. CONCLUSIONS: This case is unique due to the presence
      of multiple endocrine abnormalities and the particularities of the surgical
      anesthetic management. Intraoperative monitoring is mandatory during removal of
      an insulinoma to avoid incomplete tumor resection. Multiple challenges in one
      patient demand the knowledge, by the anesthesiologist, of each obstacle and its
      interactions in order to devise strategies to control them.

PMID- 19378537
TI  - Total intravenous anesthesia as a target-controlled infusion. An evolutive
      analysis.
AB  - BACKGROUND AND OBJECTIVES: Total intravenous anesthesia (TIVA) has seen several
      developments since it was first used. Since the synthesis of the first
      intravenous anesthetics, with the introduction of barbiturates (1921) and
      thiopental (1934), TIVA has evolved until the development of TIVA with target
      controlled infusion pumps (TCI). The first pharmacokinetic model for the use of
      TCI was described by Schwilden in 1981. From that moment on, it was demonstrated
      that it is possible to maintain the desired plasma concentration of a drug using
      an infusion pump managed by a computer. CONTENTS: The objective of this report
      was to describe the theoretical bases of TCI, propose the development of a common
      TCI vocabulary, which has not been done in Brazil and make a critical analysis of
      the current aspects of TCI in the world and in Brazil. CONCLUSIONS: The advent of
      new infusion pumps with pharmacokinetic models of remifentanil, sufentanil and
      propofol opens a new chapter in TIVA and aligns Brazil with the world tendency in
      TCI. Those systems will allow TCI of hypnotics and opioids concomitantly.
      However, the most important conclusion refers to the economy, since drugs used in
      those pumps will not be restricted to only one drug company, similar to what
      happened with propofol. Nowadays, TCI devices for the use of propofol and
      opioids, which accept any pharmaceutical presentation, with the advantage of
      changing the concentration of the drug in the syringe according to the dilution
      desired are available.

PMID- 19378538
TI  - Positioning of the anesthetized patient and cerebral perfusion: foreseeable
      catastrophes.

PMID- 19378539
TI  - A comparative study of 0.125% racemic bupivacaine (S50-R50) and 0.125% and 0.25%
      50% enantiomeric excess bupivacaine (S75-R25) in epidural anesthesia for labor
      analgesia.
AB  - BACKGROUND AND OBJECTIVES: Continuous epidural block is used for relief of labor
      pain and it is associated with a low incidence of complications. Studies with the
      levorotatory isomer of local anesthetics demonstrated that they are safer
      regarding the cardiotoxicity. The objective of this study was to compare
      analgesia and motor blockade of 0.125% bupivacaine (S50-R50) and 0.125% and 0.25%
      50% enantiomeric excess bupivacaine (S75-R25) in continuous epidural block for
      labor analgesia. METHODS: Seventy-five patients in labor participated in this
      randomized, double-blind study after signing an informed consent. Patients were
      divided in three groups: GI - 0.125% bupivacaine (S50-R50); GII - 0.125%
      bupivacaine (S75-R25) and GIII - 0.25% bupivacaine (S75-R25). RESULTS: The
      latency of analgesia, levels of sensorial blockade, volume of local anesthetic,
      duration of labor and analgesia, frequency of instrumental delivery, Apgar
      scores, or pH of umbilical cord blood showed no statistically significant
      differences. The length of time until the first rescue dose was greater and pain
      scores at 45 minutes were also greater in the 0.25% bupivacaine (S75-R25) group.
      The intensity of the motor blockade was greater in the 0.125% bupivacaine (S50
      R50) group. CONCLUSIONS: The motor blockade was less intense with bupivacaine
      (S75-R25) regardless the concentration, resulting in analgesia of better quality
      without interfering with the evolution of labor or the vitality of newborns.

PMID- 19378540
TI  - Preparation, characterization and in vitro evaluation of 50% enantiomeric excess
      bupivacaine (S75-R25)-loaded microspheres.
AB  - BACKGROUND AND OBJECTIVES: Microspheres can be used as a controlled delivery
      system to prolong the duration of action of local anesthetics. The objective of
      this study was the preparation, characterization and analysis of the in vitro
      release of 50% enantiomeric excess bupivacaine (S75-R25)-loaded microspheres.
      METHODS: Microspheres were prepared using the copolymer of polylactide-co
      glycolic acid by the spray-dryed method. RESULTS: Characterization of
      microspheres regarding their size and content were similar to the theoretical
      values. The in vitro release demonstrated a biphasic pattern. CONCLUSIONS:
      Manufacturing of 50% enantiomeric excess bupivacaine-loaded microspheres by the
      spray-dryed method with results similar to bupivacaine-loaded microspheres can be
      done.

PMID- 19378541
TI  - Topical anesthesia associated with sedation for phacoemulsification. Experience
      with 312 patients.
AB  - BACKGROUND AND OBJECTIVES: The use of topical anesthesia in cataract surgeries
      has been increasing, especially after the development of phacoemulsification. The
      objective of this study was to evaluate the efficacy of topical anesthesia
      associated with sedation for cataract extraction by phacoemulsification. METHODS:
      A prospective study was conducted with 312 patients, ASA I and II, ages 41 to 89
      years. Phacoemulsification was performed under topical anesthesia (5 minutes
      before surgery, by dripping 0.5% proximetacaine) associated with sedation
      (intravenous midazolam, 1 mg, administered 15 minutes before the surgery).
      Intravenous bolus of alfentanil, 125 microg, were administered under demand.
      Parameters, such as intraoperative pain, consumption of alfentanil, side effects,
      recovery time, and level of patient satisfaction were analyzed. RESULTS: In the
      intraoperative period, 8 (2.6%) cases of bradycardia, 4 (1.3%) of epithelial
      edema, 2 (0.65%) of nausea, and 2 (0.65%) ruptures of the posterior capsule were
      observed. In the postoperative period, 15 (4.8%) cases of nausea, 6 (1.9%) cases
      of dizziness, 2 (0.65%) of vomiting, and 1 (0.32%) case of bradycardia were
      observed. The mean time of postoperative recovery was 21.77 minutes. Consumption
      of alfentanil varied from 125 microg to 1250 microg, with a mean consumption of
      537 microg. Three hundred (96.2%) patients classified the technique as good and
      12 (3.8%), as regular. Forty-two patients complained of pain sometime during
      surgery, and 4 (1.3%) patients said that if they needed another
      phacoemulsification, they would not like to undergo the same anesthetic
      technique. CONCLUSIONS: In this study, topical anesthesia with sedation of
      patients undergoing cataract removal by phacoemulsification demonstrated to be
      effective, easy to apply, and had a very low incidence of complications.

PMID- 19378543
TI  - Anesthesia for cesarean section on a pregnant woman with hypoplasia of the distal
      aorta. Case report.
AB  - BACKGROUND AND OBJECTIVES: Maternal vascular anomalies, potentially severe for
      the fetus, can jeopardize uterine perfusion, which demands more caution by the
      anesthesiology team. The objective of this report was to demonstrate the
      anesthetic conduct for a cesarean section on a pregnant woman with hipoplasia of
      the distal aorta, just below the renal arteries, with stenosis of the renal
      artery and absence of the iliac arteries. CASE REPORT: This is a 30-year old
      patient, weighing 54 kg, on her second pregnancy, with a history of an
      uncomplicated cesarean section. During the gestational echocardiography on the
      12th week, it was observed an interruption of the distal aorta, just below the
      renal arteries. The patient was referred for coronary angiography, which
      demonstrated hypoplasia of the distal aorta, just below the renal arteries, and
      absence of the iliac arteries. During the clinical investigation, the patient
      remained asymptomatic, except for hypertension and claudication during great
      efforts. She underwent continuous epidural anesthesia and the dose of the
      anesthetic was titrated as needed for the cesarean section. Initially, 50 mg of
      0.5% bupivacaine without vasoconstrictor and 10 microg of sufentanil were
      administered. After 15 minutes, anesthesia was complemented with 25 mg of 0.5%
      bupivacaine, which was enough to achieve an adequate level of blockade. The
      cesarean section was performed without intercurrences, and the fetus was born in
      good clinical conditions. CONCLUSION: The use of continuous epidural block in
      fractionated doses demonstrated to be a safe anesthetic technique for this
      procedure because it reduces the risks of maternal hypotension, inherent to the
      spinal block, and also minimized the placentary transference of drugs, which is
      the case with general anesthesia. Titration of drugs through the epidural
      catheter allowed reaching an adequate anesthetic level for this type of surgery.

PMID- 19378542
TI  - Prophylactic antiemetic therapy for acute abdominal surgery. A comparative study
      of droperidol, metoclopramide, tropisetron, granisetron and dexamethasone.
AB  - BACKGROUND AND OBJECTIVES: It is calculated that the incidence of postoperative
      nausea and vomiting (PONV) is approximately 30%. The prophylaxis of PONV has been
      the subject of several studies, both to decrease this problem and to compare the
      cost-benefit ration of the treatment used. The objective of this study was to
      compare the efficacy of 5 antiemetic drugs with a control group in emergency
      appendectomy. METHODS: A controlled, double-blind, prospective study with 150
      patients, ASA I and II, BMI < 30, undergoing appendectomy, was undertaken.
      Patients were divided in six groups: Group 1 (n = 25): 5 mL of normal saline;
      Group 2 (n = 25): 0.625 mg of droperidol; Group 3 (n = 25): 20 mg of
      metoclopramide; Group 4 (n = 25): 5 mg of tropisetron; Group 5 (n = 25): 1 mg of
      granisetron; Group 6 (n = 25): 4 mg of dexamethasone. Monitoring included ECG non
      invasive blood pressure, O2 saturation, P(ET)CO2, anesthetic gas analyzer and
      peripheral nerve stimulator. The presence of PONV complications and the degree of
      satisfaction in the first 48 hours were evaluated. RESULTS: The incidence of PONV
      in the droperidol group was 4% while in the granisetron, tropisetron and
      metoclopramide groups it was 12% (p < 0.05). The dexamethasone group had a 24%
      incidence and the control group 28%. CONCLUSIONS: Low doses of droperidol were
      more effective in the prophylaxis of PONV in emergency appendectomy than the
      other drugs.

PMID- 19378544
TI  - Ultrasound-guided ileoinguinal and ileohypogastric nerve block associated with
      general anesthesia. Case report.
AB  - BACKGROUND AND OBJECTIVES: Outpatient surgeries are becoming more frequent.
      Ilioinguinal and iliohypogastric nerve block has been used in postoperative
      analgesia of patients undergoing outpatient inguinal herniorrhaphy. Ultrasound
      guided regional anesthesia increases the accuracy of deposition of the local
      anesthetic around the nerves. The objective of this report was to present a case
      of ultrasound-guided ilioinguinal and iliohypogastric nerve block for outpatient
      inguinal herniorrhaphy. CASE REPORT: A 36-year old male patient, 74 kg, physical
      status ASA I, was scheduled for inguinal herniorrhaphy. Ultrasound-guided
      iliohypogastric and ilioinguinal nerve block was accomplished with 0.5%
      ropivacaine, followed by total intravenous anesthesia. The patient was discharged
      from the hospital 4 hours after the procedure with a pain score of 3 in the
      Verbal Analogue Scale. CONCLUSION: Ultrasound-guided iliohypogastric and
      ilioinguinal nerve block in patients undergoing outpatient inguinal herniorrhaphy
      can be done as an aid to postoperative analgesia.

PMID- 19378545
TI  - Blind nasotracheal intubation in awaken patient scheduled for hemimandibulectomy.
      Case report.
AB  - BACKGROUND AND OBJECTIVES: Several resources can be used for the approach of the
      airways. Maintaining a patient awake when control of ventilation/oxygenation is
      uncertain is an option when intubation is doubtful. Blind nasotracheal intubation
      (NTI) is an alternative to fiberoptic endoscopy. CASE REPORT: A 75-year old
      patient, weighing 56 kg, was scheduled for hemimandibulectomy; she presented
      cervical immobility secondary to arthrodesis, mouth opening of 2.2 cm, moderate
      retrognatism, voluntary protrusion of the mandible was absent, mentostemal
      distance of 11 cm and mento-thyroid distance of 6 cm, therefore receiving a score
      of 5 on the Wilson scale. The patient signed an informed consent after being
      informed about the procedure. After monitoring and oxygenation, continuous
      infusion of dexmedetomidine was initiated. Superior and inferior laryngeal nerve
      block was performed with 2.0% lidocaine without vasoconstrictor and the
      hypopharinx was anesthetized with a lidocaine spray. Before NTI, ondansetron,
      midazolam, fentanyl, and droperidol were administered and the patient remained
      awake and cooperative. Nasal insertion of the tracheal tube was oriented by its
      opacification and respiratory sounds and the placement was confirmed by pulmonary
      auscultation and capnography. Continuous infusion of propofol and remifentanil
      was instituted, vecuronium was administered and controlled ventilation was
      initiated. The surgery lasted 60 minutes without intercurrences. At the end, the
      patient was breathing spontaneously, so she was extubated and transferred to the
      recovery room from where she was discharged without any complaints. CONCLUSION:
      Nasotracheal intubation is an alternative to fiberoptic endoscopy when safety and
      control of the airways is uncertain. Informing the patient about the procedure
      was essential. Safety was assured and respiratory depression and hemodynamic
      instability was not observed.

PMID- 19378546
TI  - Intraoperative pulmonary barotrauma during ophthalmologic surgery. Case report.
AB  - BACKGROUND AND OBJECTIVES: Nowadays, severe anesthetic complications caused by
      the improper use of mechanical ventilators are rare. However, technical details
      even in recent models can be a trap for the anesthesiologist and threaten patient
      safety. The objective of this report was to demonstrate the importance of a
      careful analysis of the device to be used, as well as to detect and treat
      intraoperative tension pneumothorax. CASE REPORT: A 16-year old female patient,
      physical status ASA I, underwent corneal conjunctival covering under general
      anesthesia. Anesthesia was maintained with isoflurane and controlled mechanical
      ventilation. No abnormalities were observed during anesthesia. At the final phase
      of the surgery, after mobilizing the anesthesia device to start the awakening
      process, the patient developed hypoxia, hypertension and ventilatory
      difficulties. After removal of the sterile drapes from the surgical field,
      subcutaneous emphysema was evident in the face, neck and upper limb. The tracheal
      cannula, which contained blood, was changed. A chest Xray confirmed the diagnosis
      of pneumothorax that was immediately drained. Inspection of the equipment
      revealed the presence of a kink in the tubing connecting the inferior portion of
      the canister to the equipment itself caused by mobilization of the articulated
      arm, blocking the normal flow of gases and leading to pulmonary barotrauma.
      CONCLUSIONS: The development of tension pneumothorax during general anesthesia
      with positive pressure ventilation should always be considered. Several factors
      can contribute to the development of this condition, which should be considered
      when they are present during surgeries. The anesthesia equipment should be
      examined carefully to detect potential causes of anesthetic complications.

PMID- 19378547
TI  - Right atrial myxoma associated with acute cor pulmonale. Case report.
AB  - BACKGROUND AND OBJECTIVES: Atrial myxomas are the most common type of primary
      intracardiac tumors. Although they are benign, it is recommended its immediate
      removal as soon as the diagnosis is confirmed, since they are associated with
      tumor embolization and their harmful consequences. The objective of this report
      was to present the case of an intracardiac tumor of rare location (right atrium)
      that developed intraoperative embolization and to alert anesthesiologists for the
      possibility of this complication, besides discussing the anesthetic conduct. CASE
      REPORT: A male patient, 42 years old, presented with a large mass in the right
      atrium, being scheduled for removal of the tumor. Anesthetic induction consisted
      of ethomidate, fentanyl and rocuronium bromide and it was maintained with
      isoflurane and fentanyl. Intraoperatively, the patient developed acute cor
      pulmonale secondary to tumor embolization, with the immediate institution of
      support measures and cardiopulmonary bypass. The remaining of the surgery was
      uneventful and the patient was discharged on the 7th postoperative day in good
      conditions. CONCLUSIONS: Although intracardiac myxoma is a benign tumor, it can
      be associated with severe and even fatal complications. Knowledge of the disease
      is important for the proper management of those patients by the anesthesiologist,
      as well as to diagnose and treat possible intraoperative complications.

PMID- 19378548
TI  - Atelectasis during anesthesia: pathophysiology and treatment.
AB  - BACKGROUND AND METHODS: The incidence of intraoperative pulmonary collapse is
      elevated in patients undergoing surgery under general anesthesia with muscle
      relaxation/paralysis. This complication is associated with worsening
      intraoperative gas exchange and, in some cases, the need for prolonged
      postoperative respiratory support. The objective of this report was to review the
      pathophysiological aspects of atelectasis during general anesthesia and possible
      therapeutic maneuvers that could prevent and treat this complication. CONTENTS:
      This review discusses the concepts about the incidence of intraoperative
      atelectasis, factors that influence their development, both mechanical and those
      related to mechanical ventilator settings during the surgery, diagnostic
      criteria, and strategies to prevent and treat this complication. CONCLUSIONS:
      Understanding of the mechanisms related with the development of intraoperative
      pulmonary collapse, as well as its treatment, can contribute to reduce the
      incidence of postoperative pulmonary complications, the length of recovery and
      hospital costs.

PMID- 19378550
TI  - Stereochemistry of free boranes and heteroboranes from electron scattering and
      model chemistries.
AB  - The development of modern computational methods, linked to improved methods for
      analysis of experimental gas-phase structural data, has allowed the
      stereochemistry of many boranes and heteroboranes to be determined with great
      accuracy over the past two decades. Many of these compounds have been prepared in
      the Institute of Inorganic Chemistry of the Academy of Sciences of the Czech
      Republic, and gas-phase electron diffraction (GED) data have been obtained mainly
      at the University of Edinburgh. Structural tools based on the concerted use of
      GED and computations of the geometries and "B chemical shifts (MOCED, SARACEN)
      have also been employed. The results of this extended programme of research are
      reviewed here. Many different closo-, nido-, arachno-, and hypho-geometrical
      shapes, as well as some that do not obey Wade's rules, are included. The outlook
      for the future of this type of structural chemistry research is assessed.

PMID- 19378549
TI  - Turner syndrome and anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Turner syndrome is a frequent and complex genetic
      abnormality affecting women, being associated with a wide variety of anatomical
      and physiological changes, especially related with the airways and cardiovascular
      system. The objective of this report was to review the anatomopathologic changes
      of this syndrome that concern the anesthesiologist the most, discuss the
      perioperative management and review the literature regarding the anesthetic
      conduct in those patients. CONTENTS: Turner syndrome is a genetic disorder
      characterized by an abnormality in the number or morphology of the sex
      chromosome. The most frequent abnormality is the absence of a sex chromosome,
      resulting in the 45X karyotype and a phenotype composed of gonadal dysgenesis.
      The main anatomo-physiological changes pertaining the anesthesiologist include a
      short neck, and maxillary and mandibular hipoplasia, which might be responsible
      for difficult airways. The shorter length of the trachea, as well as the higher
      location of its bifurcation, can predispose to bronchial intubation and
      accidental endotracheal extubation when the tracheal cannula is under traction.
      The presence of cardiopathies, endocrine and gastrointestinal disorders, liver
      and kidney changes, as well as osteoarticular involvement, besides ophthalmologic
      and hearing impairments, are very frequent, and should be detected during the pre
      anesthetic evaluation. General or regional anesthesia seems to be safe for those
      patients. CONCLUSIONS: Turner syndrome is a genetic abnormality with important
      anatomo-physiological abnormalities important to the anesthesiologist. The
      knowledge of this disorder allows for a safer anesthetic management with low
      perioperative morbimortality.

PMID- 19378551
TI  - The adsorbate structure of ferrocene inside [Al(OH)(bdc)]x (MIL-53): a powder X
      ray diffraction study.
AB  - Ferrocene is strongly adsorbed by the highly porous metal-organic framework
      compound [Al(OH)(bdc)l], (MIL-53; bdc = 1,4-benzenedicarboxylate). The structure
      of the crystalline phase {[Fe(eta5-C5H5)2][Al(OH)(bdc)]2}x, was determined by X
      ray powder diffraction and Rietveld methods. The ferrocene molecules are arranged
      in a 1D chain-like fashion and their cyclopentadienyl rings are oriented almost
      parallel to the O3Al faces of the {AlO6}) octahedra without pi-stacking to the
      bdc.

PMID- 19378552
TI  - Tris(pyrazolyl)methane 99mtc tricarbonyl complexes for myocardial imaging.
AB  - Novel ether-containing tris(pyrazolyl)methane chelators stabilize thefac
      [99mTc(CO)3]+ moiety providing complexes with significant, fast and stable heart
      uptake, together with a extremely fast liver clearance.

PMID- 19378553
TI  - Bifunctional dithiocarbamates: a bridge between coordination chemistry and
      nanoscale materials.
AB  - A dithiocarbamate-based methodology is employed to prepare linked
      heteromultimetallic complexes and then further exploited in the surface
      functionalisation of gold nanoparticles.

PMID- 19378554
TI  - Transition metal alkynyl complexes by transmetallation from Au(C[triple
      bond]CAr)(PPh3) (Ar = C6H5 or C6H4Me-4).
AB  - Facile acetylide transfer reactions take place between gold(I) complexes
      Au(C[triple bond]CAr)(PPh3) (Ar = C6H5 or C6H4Me-4) and a variety of
      representative inorganic and organometallic complexes MXL, (M = metal, X =
      halide, L, = supporting ligands) featuring metals from groups 8-11, to afford the
      corresponding metal-alkynyl complexes M(C[triple bond]CR)Ln in modest to good
      yield. Reaction products have been characterised by spectroscopic methods, and
      molecular structure determinations are reported for Fe(C[triple bond]CC6H4Me
      4)(dppe)Cp, Ru(C[triple bond]CC6H4Me-4)(dppe)Cp*, Ru(C=CCsF,)(l2-O2)(PPh3)Cp*,
      Ir(C-CC6H4Me-4)(eta2-O2)(CO)(PPh3), Ni(C[triple bond]CC6H4Me-4)(PPh3)Cp and trans
      Pt(C[triple bond]CAr)2L2 (Ar = C6H5, L = PPh3; Ar = C6H4Me-4, L = PPh3, PMe3).

PMID- 19378555
TI  - A novel hemilabile calix[4],quinoline-based P,N-ligand: coordination chemistry
      and complex characterisation.
AB  - The synthesis of the calix[4]arene-based P,N-ligand 3 (5,11,17,23-tetra-tert
      butyl-25-[(2-quinolylmethyl)oxy]-26,27,28-(mu3-phosphorustrioxy)calix[4]arene),
      in which the nitrogen atom-containing moiety has been introduced at the lower rim
      of the cavity prior to P-functionalisation, is described and its coordination
      properties investigated. In the crystal structure, the calix[4]-cavity adopts a
      cone conformation with an exo orientation of the phosphorus lone pair enabling P
      N chelation. 1H, 13C, 31P and 1H{15N} HMQC NMR spectra indicated that, in
      complexes [PdCl(CH3)(3)] (4) and [Rh(CO)Cl(3)] (5), ligand 3 coordinates in a
      chelating fashion, while in cis-[PtC12(3)2] (6) and [Rh(acac)(CO)(3)] (7) it
      behaves as a monodentate ligand, coordinating via the phosphorus atom only. X-Ray
      crystal structure determinations were performed for [PdCl(CH3)(3)] (4) and cis
      [PtCl2(3)2] (6). The cationic Pd complex [Pd(CH3)(CH3CN)(3)][PF5] (8) was found
      to be active in a CO/ethylene copolymerisation reaction. Good selectivities were
      observed for the Pd-catalysed allylic alkylation of cinnamyl acetate with in situ
      prepared catalysts. [Rh(acac)(CO)2] modified with ligand 3 catalyses the
      hydroformylation of 1-octene with low selectivities towards linear aldehydes.
      High-pressure NMR experiments on the hydrido carbonyl rhodium(3) were
      inconclusive, different species were formed.

PMID- 19378557
TI  - Azidoformamidinium and 5-aminotetrazolium dinitramide-two highly energetic
      isomers with a balanced oxygen content.
AB  - The highly energetic isomers azidoformamidinium dinitramide (1) and 5
      aminotetrazolium dinitramide (2) were synthesized by the reaction of potassium
      dinitramide and azidoformamidinium perchlorate and 5-aminotetrazolium
      perchlorate, respectively. Both compounds are characterized by an oxygen balance
      of omega=0. In addition, 1H-tetrazolium dinitramide (3) and 2-methyl-5
      aminotetrazolium dinitramide (4) were synthesized using 1H-tetrazolium
      perchlorate (5) and 2-methyl-5-aminotetrazolium perchlorate. A full
      characterization of the chemical properties (single-crystal X-ray diffraction, IR
      and Raman spectroscopy, multinuclear NMR spectroscopy, differential scanning
      calorimetry and mass spectrometry) as well as of the energetic characteristics is
      given in this work. The heats of formation were calculated (CBS-4M) in an
      extensive computational study. The detonation parameters of compounds 1-4 were
      computed using the EXPLO5 software resulting in auspicious values for potential
      applications as high explosives. For 2 this was confirmed by a "Koenen" steel
      sleeve test using a critical diameter of 10 mm. In addition, the sensitivities
      were tested using the BAM drop hammer, BAM friction tester and an electrical
      spark device. Finally, the synthesis and characterization, including the X-ray
      structure of the highly hygroscopic 1H-tetrazolium perchlorate (5), is given in
      this work.

PMID- 19378556
TI  - Weakly coordinating counter-ions for highly efficient catalysis of intramolecular
      hydroamination.
AB  - A series of cationic rhodium(I) and iridium(I) complexes of the type [M(L[symbol:
      see text]L)(C2)]BAr(F)24 (where M = Rh or Ir, L[symbol: see text]L = bis(pyrazol
      1-yl)methane (bpm), bis(N-methylimidazol-2-yl)methane (bim) or 1-(2
      (diphenylphosphino)ethyl)-3,5-diphenylpyrazole (Ph2PyP), C2 = 1,5-cyclooctadiene
      (COD) or (CO)2 and BAr(F)24 = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate)
      were synthesised in good yields. The solid-state structure of a number of
      complexes, including [Ir(Ph2PyP)(COD)]BAr(F)24, [Ir(bpm)(COD)]BAr(F)24 and
      [Ir(bim)(COD)]BAr(F)24 was determined using X-ray crystallography. The efficiency
      of the complexes as catalysts for the intramolecular hydroamination of 4-phenyl-3
      butyn-1-amine, 4-pentyn-1-amine and 2-(2-phenylethynyl)aniline was established.
      The incorporation of the BAr(F)24- counter-ion in the Rh(I) and Ir(I) complexes
      was found to significantly improve the catalytic activity of the complexes,
      compared to the analogous Rh(I) and Ir(I) complexes containing BPh4- as the
      counter-ion. Excellent conversions were achieved for the cyclisation of 2-(2
      phenylethynyl)aniline to 2-phenylindole using [Rh(bpm)(CO)2]BAr(F)24 as a
      catalyst. The use of a microwave reactor for enhancing the catalysed reactions
      was also investigated.

PMID- 19378558
TI  - Monomeric malonate precursors for the MOCVD of HfO2 and ZrO2 thin films.
AB  - New Hf and Zr malonate complexes have been synthesized by the reaction of metal
      amides with different malonate ligands (L = dimethyl malonate (Hdmml), diethyl
      malonate (Hdeml), di-tert-butyl malonate (Hdbml) and bis(trimethylsilyl) malonate
      (Hbsml)). Homoleptic eight-coordinated monomeric compounds of the type ML4 were
      obtained for Hf with all the malonate ligands employed. In contrast, for Zr only
      Hdmml and Hdeml yielded the eight-coordinated monomeric compounds of the type
      ML4, while using the bulky Hdbml and Hbsml ligands resulted into mixed alkoxo
      malonato six-coordinated compounds of the type [ML2(OR)2]. Single crystal X-ray
      diffraction studies of all the compounds are presented and discussed, and they
      are found to be monomeric. The complexes are solids and in solution, they retain
      their monomeric nature as evidenced by NMR measurements. Compared to the
      classical beta-diketonate complexes, [M(acac)4] and [M(thd)4] (M = Hf, Zr; acac:
      acetylacetonate; thd: tetramethylheptadione), the new malonate compounds are more
      volatile, decompose at lower temperatures and have lower melting points. In
      particular, the homoleptic diethyl malonate complexes of Hf and Zr melt at
      temperatures as low as 62 degrees C. In addition, the compounds are very stable
      in air and can be sublimed quantitatively. The promising thermal properties makes
      these compounds interesting for metal-organic chemical vapor deposition (MOCVD).
      This was demonstrated by depositing HfO2 and ZrO2 thin films successfully with
      two representative Hf and Zr complexes.

PMID- 19378559
TI  - Experimental charge density in an oxidized trinuclear iron complex using 15 K
      synchrotron and 100 K conventional single-crystal X-ray diffraction.
AB  - The experimental electron density distribution in a crystal consisting of the
      simplest conceivable trinuclear carboxylate-bridged iron-mu3-oxo dianion with two
      alpha-picolinium cations has been determined using both synchrotron (15 K) and
      conventional (100 K) X-ray diffraction data. The constituent trinuclear oxo
      centered molecule consists of six mu2-bridging formate groups between the iron
      pairs, while the axial ligand for all iron atoms is another formate group. The
      compound {[FeO(HCOO)5(HCOO)3]2-.H2O.2(alpha-CH3NC5H5)}, (1) crystallizes in the
      monoclinic space group P2(1)/m with charge assisted hydrogen bonds linking the
      alpha-picolinium cations to the trinuclear groups. The chemical bonding in the
      weakly asymmetric Fe3O-core of 1 has been examined through the use of the quantum
      theory of atoms in molecules, and in combination with experimental d-orbital
      populations, a significant electron sharing is observed between the Fe atoms and
      the central oxygen. The central oxygen exhibits clear sp2 hybridization, and the
      iron atoms have valence shell charge concentrations in all metal-ligand bond
      directions. The relative bond strengths are evaluated based upon the charge
      density distribution and found to be in accordance with the geometrical results.
      Integrated group charges follow expectations from formal chemical valences.

PMID- 19378560
TI  - Comparative study of the constitution and chiroptical properties of emissive
      terbium and europium complexes with a common tetraazatriphenylene sensitiser; the
      nature of the sensitiser determines quenching sensitivity and cellular uptake.
AB  - Six pairs of Eu(III) and Tb(III) complexes of macrocyclic ligands, incorporating
      a common tetraazatriphenylene sensitiser, have been examined in terms of their
      solution structure, sensitivity to excited state quenching, protein affinity,
      cell toxicity and preliminary cell localisation profiles. A complex with three
      (S)-phenylalanine-derived ligating groups possesses distinctive 1H NMR, Eu
      emission and circularly polarised emission properties, consistent with a unique A
      configuration in the 9-coordinate complex, where an amide carbonyl group occupies
      the capping position of the coordination polyhedron. Each complex possesses
      similar sensitivity to quenching by ascorbate, urate and iodide, has similar
      toxicity behaviour and shows a common intracellular localisation profile that is
      consistent with compartmentalisation in lysosomes or late endosomes. Such
      behaviour accords with the hypothesis that it is the nature of the sensitising
      moiety that determines each of these properties.

PMID- 19378561
TI  - Universal spectrochemical series of six-coordinate octahedral metal complexes for
      modifying the ligand field splitting.
AB  - We studied a novel universal spectrochemical series of six-coordinated octahedral
      3d transition metal complexes, which can be used for any combination of central
      metal atom and ligand molecules. A two dimensional spectrochemical series could
      be used to estimate the ligand field splitting energy of not only known compounds
      but also the unknown compounds. Therefore, it should be possible to control the
      physical properties, such as the electronic and magnetic properties and the
      optical phenomena of octahedral transition metal complexes by modifying the
      ligand field splitting.

PMID- 19378562
TI  - The N-terminal soluble domains of Bacillus subtilis CopA exhibit a high affinity
      and capacity for Cu(I) ions.
AB  - CopA from Bacillus subtilis is a Cu(I)-transporting P-type ATPase involved in
      resistance to high levels of environmental copper. At its N-terminus are two
      soluble domains, a and b, that, when generated in isolation from the membrane
      part, have previously been shown to exhibit unusual Cu(I)-binding behaviour: at
      >1 Cu(I) per CopAab the protein dimerises, resulting in the formation of a
      species with luminescence properties characteristic of a solvent-shielded Cu(I)
      cluster. Further insight into the Cu(I)-binding properties of CopAab are now
      reported. We demonstrate that the initial binding of Cu(I) occurs with very high
      affinity (K = -4 x 10(17) M(-1)) and that CopAab can accommodate up to 4 Cu(I)
      per protein and remains dimeric at higher Cu(I)-loadings. Fitting of UV-visible,
      near UV CD, fluorescence and luminescence spectroscopic titration data supports a
      model in which Cu(I) binds sequentially to CopAab, and also provides estimates of
      the association constants for Cu(I)-binding and dimerisation steps. Finally, low
      molecular weight thiols are shown not to affect the initial binding of Cu(I), but
      significantly influence binding at levels >1 Cu(I) per CopAab such that
      dimerisation is inhibited, though not abolished.

PMID- 19378563
TI  - Synthesis and reactivity of metal carbene complexes with heterobiaryl spacer
      substituents.
AB  - Mono- and binuclear Fischer carbene complexes, [M(CO)5{C(OR)Ar-ArX}], X = H,
      {C(OR)M'(CO)5}; M, M' = W or Cr; R = Me, Et or (CH2)4OMe; Ar = thiophene, N
      methylpyrrole or furan units 1-20, were synthesized. For this purpose, mono-, bi-
      or stepwise lithiated bithiophene, N,N'-dimethylbipyrrole, thienylfuran and N
      methyl(thienyl)pyrrole were reacted with chromium and tungsten hexacarbonyl
      precursors. Dilithiation in the 2- and 9-positions of N-methyl(thienyl)pyrrole
      could not be achieved. Alkylation of acyl metallates with triethyloxonium
      tetrafluoroborate or methyl trifluoromethanesulfonate in THF afforded not only
      the expected carbene complexes with ethoxy or methoxy substituents, but in the
      case of bithiophene with methyl trifluoromethanesulfonate, carbene complexes with
      alkoxy substituents incorporating a ring-opened tetrahydrofuran moiety. X-Ray
      crystallographic structure determinations were performed on
      [W(CO)5{C(OMe)(thienylfuran)}] (14), [W(CO)5{C(OMe)(N-methylthienylpyrrole)}]
      (20) and [{W(CO)5}2{mu-C(OEt)(N,N'-dimethylbipyrrolylC(OEt)}] (12) to assess the
      role of the heterobiaryl substituent on the structural features of the carbene
      ligand in the complexes. Complexes [{Cr(CO)5}2{mu-C(OMe)bithienylC(OEt)}] (3),
      [(CO)5Cr{mu-C(OMe)bithienylC(OMe)}W(CO)5] (5) and [{Cr(CO)5}2 {mu
      C(OMe)thienylfuranC-(OMe)}] (15) were reacted with 3-hexyne to study their
      behaviour in benzannulation reactions. The major products generated by the
      biscarbene complexes were regio-selectively determined by the nature of the metal
      site and that of the heteroatom in the arene rings. The monocarbene complexes
      [Cr(CO)5{C(OMe)thienylfuran] (13) and [Cr(CO)5{C(OEt)(N-methylthienylpyrrole)}]
      (19) were refluxed in THF for 2 hours in the presence of [Pd(PPh4)4] to afforded
      the carbene-carbene coupled olefinic products and small amounts of the
      corresponding 2-ethyl(biheteroaryl)acetate. By contrast, the biscarbene complex
      of thienylfuran (15), afforded only the 2,9-diester of thienylfuran.

PMID- 19378564
TI  - Luminescence color change of a platinum(II) complex solid upon mechanical
      grinding.
AB  - The mechanochemical behavior of Pt(5dpb)Cl (5dpbH = 1,3-di(5-methyl-2
      pyridyl)benzene) was investigated in terms of solid-state luminescence. The
      yellow luminescence of the crystalline complex changed to orange when grinding
      into fine powder on a glass substrate with a spatula. A broad emission band,
      which was not detected for the crystal, was observed at around 670 nm for the
      powder. The powder X-ray diffraction (XRD) pattern was the same as that
      calculated from X-ray crystallographic data of the single crystal. A broad band
      appeared within 100 ns after laser excitation accompanied by quenching of the
      s(pi,pi*) emission of Pt(5dpb)Cl, which was then weakened with decreasing
      temperature and disappeared below 120 K. The phenomenon was very similar to the
      excimer formation observed in solution. A related complex, Pt(dpb)Cl (dpbH = 1,3
      di(2-pyridyl)benzene), also exhibited luminescent mechanochromism. However, the
      broad emission that appeared upon grinding still remained at 77 K, and XRD showed
      that the ground sample of Pt(dpb)Cl was amorphous.

PMID- 19378565
TI  - Ruthenium xantphos complexes in hydrogen transfer processes: reactivity and
      mechanistic studies.
AB  - The in situ combination of [Ru(PPh3)3(CO)H2] with xantphos is catalytically
      active for the alkylation of alcohols with the ketonitrile (t)BuC(O)CH2CN in a
      model oxidation-Knoevenagel-reduction process. The precursor complex
      [Ru(xantphos)(PPh3)(CO)H2] was isolated and reacted with stoichiometric amounts
      of PhCH2OH and PhCHO. Under these conditions, the alcohol is decarbonylated to
      afford [Ru(xantphos)(CO)2H2] and finally [Ru(xantphos)(CO)3], both of which prove
      to be less active for catalysis than the starting complex. The reactivity of the
      xantphos system contrasts with that of [Ru(dppp)(PPh3)(CO)H2], which is
      catalytically inactive for the Knoevenagel reaction and fails to show any
      stoichiometric reactivity with alcohols.

PMID- 19378566
TI  - Foam-like, microstructural SnO2-carbon composite thin films synthesized via a
      polyol-assisted thermal decomposition method.
AB  - Foam-like, microstructural SnO2-carbon composite thin films were synthesized by
      refluxing SnCl2.2H2O in ethylene glycol (EG) at 195 degrees C for 4 h under
      vigorous stirring in air followed by thermal decomposition of the as-synthesized
      precursor solution, whereby the products were deposited onto stainless steel (SS)
      substrates. Subsequently, the decomposed product, which now consists only of the
      microstructural SnO2-carbon composite thin film, without the addition of any
      binder and carbon black conductive agent, was directly applied as an anode
      material for use in a Li-ion rechargeable battery. Physical and electrochemical
      characterizations of the as-synthesized thin films were carried out. The foam
      like, microstructural SnO2-carbon composite thin films that undergo thermal
      decomposition in air at 300 degrees C demonstrated the best cyclability,
      delivering a specific discharge capacity of approximately 496 mAh g(-1) beyond
      100 cycles. We believe that the presence of a uniform, SnO2-carbon network
      throughout the foam-like thin film, acts not only as an improved conducting
      network but also buffered the volume expansion upon Li-Sn alloying, resulting in
      a much improved cycling of the composite thin film electrode.

PMID- 19378567
TI  - Nitrene transfer reactions catalysed by copper(I) complexes in ionic liquid using
      chloramine-T.
AB  - The complex [Tpm(*,Br)Cu(NCMe)]BF4 (Tpm(*,Br) = HC(3,5-Me2-4-Br-pyrazolyl)3)
      catalyses the aziridination of alkenes and the amidation of cyclic ethers with
      chloramine-T as the nitrene source and the ionic liquid [bmim]PF6 as the reaction
      medium (bmim = 1-n-butyl-3-methylimidazolium). High conversions have been
      obtained over several cycles of catalyst recovery and reuse.

PMID- 19378568
TI  - SCHIP--leading off the 2009 health care legislation.

PMID- 19378569
TI  - Comparing three methods of assessing peripheral perfusion in critically ill
      children.
AB  - BACKGROUND: Evaluation of peripheral perfusion is a standard practice in
      pediatric intensive care units (PICUs), which includes the qualitative assessment
      of foot warmth. The perfusion indicator, derived from the pulse oximetry signal,
      is available, along with some bedside monitors. OBJECTIVES: To describe the
      correlation between RN qualitative assessment of foot warmth, measured foot
      temperature, and perfusion indicator. METHODS: Simultaneous measurements of
      qualitative foot warmth, measured foot temperature, and perfusion indicator value
      were obtained on 39 critically ill children ages newborn to 18 years, at least
      every 2 hours for 48 hours, with 859 measurements completed. RESULTS: There was a
      positive correlation between all three parameters (p = < 0.0001); however, there
      was a large amount of variability within groups. CONCLUSION: Qualitative
      assessment of foot warmth and peripheral perfusion indicator may be helpful in
      assessing the perfusion in critically ill pediatric patients, but neither is
      predictably specific as compared to measured foot temperature.

PMID- 19378570
TI  - Nasogastric tube placement verification in pediatric and neonatal patients.
AB  - This article reports an evidence-based practice project using the Iowa Model of
      Evidence-Based Practice to Promote Quality Care for a common nursing procedure,
      nasogastric tube placement verification in children. Little research exists
      regarding the care of nasogastric tubes in children, and traditional verification
      methods prevail. Auscultation of air insufflation over the abdomen is still used
      to check placement in many settings, despite research dating back to the 1980s
      questioning this approach. X-ray remains the only certain way to verify
      placement, but getting an X-ray before each feeding would be costly and
      impractical. Additional bedside methods are needed. Project results demonstrate a
      decrease (93.3% to 46.2%) in the use of auscultation and improved use of other,
      more reliable methods to determine nasogastric tube placement. Changing practice
      can be challenging. However, with persistence and re-infusion, this project
      provides an important example of how the evidence-based practice process leads to
      excellence and improves patient care.

PMID- 19378571
TI  - Everybody needs a break! Responses to a playgarden survey.
AB  - The role of outdoor activity in health and development warrants attention as an
      important feature of quality health care environments. This study of visitor
      perceptions of a playgarden located in a pediatric and women's health care
      facility resulted in 52 completed surveys from hospital staff and parents. Most
      respondents indicated high levels of agreement to questions related to their
      general experience. The main reason stated for visiting the playgarden revolved
      around the need for "a break". Time spent outdoors was appreciated relative to
      specific features, such as the natural environment, play equipment, furniture,
      and the atmosphere of the outdoors. Access to outdoor spaces and play are
      important features of the principle of normalization and also serve as an avenue
      for the promotion of healthy lifestyles.

PMID- 19378572
TI  - Spirituality in well and ill adolescents and their parents: the use of two
      assessment scales.
AB  - The literature supporting a relationship between religion/spirituality and
      physical/mental health has led to recommendations that health professionals
      attend to these issues in patient assessment and intervention. Many studies
      indicate that spiritual issues are important to adolescents, especially those
      with physical and/or psychological health concerns. Although several instruments
      have been developed to measure religion/spirituality in adults, no validated
      instrument currently exists for assessing this concept in children or
      adolescents. The applicability of two adult scales, the SIBS and the SWBS, were
      assessed to explore the spiritual well-being of adolescents by comparing
      spirituality scores of 38 chronically ill and 38 healthy adolescents and their
      parents. No significant difference was found between ill and well adolescents on
      either scale. Parents scored significantly higher than adolescents on both
      scales. Although this could indicate that parents have greater spiritual well
      being than their children, these two findings taken together suggest these
      measures may be insufficiently sensitive measures of spirituality in childhood.
      This is supported by the finding that most adolescents and their parents felt
      both scales to be ineffective measures of adolescent spirituality. The authors
      concluded that a more specific scale should be developed for measuring
      spirituality in the young, especially those with chronic illness. Such an
      instrument might best be developed through a combination of qualitative and
      quantitative research methods.

PMID- 19378573
TI  - Factors influencing the onset of childhood obsessive compulsive disorder.
AB  - Childhood obsessive compulsive disorder (OCD) was once considered a rare
      childhood condition, although recent epidemiological data rank OCD as the fourth
      most common psychiatric disorder, making it twice as common as panic disorder or
      schizophrenia (Barrett & Healy, 2003). The available literature indicates that
      OCD affects children and adolescents at a prevalence rate of up to 4%. Early
      onset of OCD is associated with a significant increase in the rate of persistence
      of this disorder (Geller, 2006). Among adults with OCD symptoms, one-third to one
      half develop symptoms before or during adolescence (March, Franklin, Nelson, &
      Foa, 2001). OCD, like most psychiatric disorders, is believed to be influenced by
      biological, psychological, and social interactions with regard to the onset and
      course of illness (Cromer, Schmidt, & Murphy, 2007). Exploring factors
      influencing the onset of symptoms is essential to early treatment and the
      reduction of suffering in children and adolescents (Douglass, Moffitt, Dar,
      McGee, & Silva, 1995). Early identification and treatment in childhood may also
      reduce adult morbidity related to this disorder (March et al., 2001). An overview
      of the predominant theories in biomedical, behavioral, and psycho-social models
      are presented, supporting an interdisciplinary approach to the treatment of OCD
      in children.

PMID- 19378574
TI  - Advising families on AD/HD: a multimodal approach.
AB  - Nurses who interact with families having children with attention deficit
      hyperactivity disorder (AD/HD) are perfectly poised to help them understand
      optimal AD/HD management. While medication can be important in managing AD/HD
      symptoms, many times it is not a sufficient treatment. A medical examination and
      a comprehensive neuropsychological or psycho-educational evaluation are important
      to establish the diagnosis and identify or rule out competing diagnoses and
      potential co-morbid conditions. A comprehensive evaluation will also lay the
      groundwork for planning accommodations in school and supports at home that will
      best facilitate an individual child's learning and development. Nurses can
      encourage comprehensive evaluations, educate parents about school advocacy, and
      assist families in understanding ways in which changes in parenting style and the
      home environment can benefit a child with AD/HD. Nurses can also educate families
      about the varied professionals and range of resources helpful in managing AD/HD
      and improving outcomes.

PMID- 19378575
TI  - Tinea capitis: diagnostic criteria and treatment options.
AB  - Tinea capitis is a fungal infection involving the hair shaft of the scalp. It is
      commonly referred to as ringworm and occurs primarily in children. Treatment with
      a systemic anti-fungal rather than topical treatment is required. Currently, two
      medications, griseofulvin (Grifulvin) and terbinafine (Lamisil Granules), are FDA
      approved to treat tinea capitis. Treatment with griseofulvin is usually 6 to 8
      weeks, while treatment with terbinafine requires 6 weeks. There are other
      medications currently not FDA-approved to treat tinea capitis that have similar
      cure rates and shorter durations of treatment for tinea capitis, and as a result,
      are being used off-label. This article reviews the research-based literature
      related to the treatment of tinea capitis with various pharmacologic agents.

PMID- 19378576
TI  - Nebraska Safe Haven Laws: a feminist historical analysis.
AB  - The Nebraska Safe Haven Laws have been a fervent topic of discussion during 2008.
      Rather than identifying that newborn infants (born to those women not wishing to
      parent) could be dropped off at a safe haven in the first day of life, there was
      inadvertently no specified end date in Nebraska law. To the surprise of many,
      children in teen years and from throughout the country were brought to Nebraska's
      doors. This article examines what that means for women and children through the
      lens of a feminist historian.

PMID- 19378577
TI  - Administration of hypotonic solutions vs. isotonic solutions in hospitalized
      children.

PMID- 19378578
TI  - Short stature in a 6-year-old female. Turner syndrome.

PMID- 19378579
TI  - Implementing evidence-based treatment plans: one health system's experience to
      standardize order sets.

PMID- 19378580
TI  - Comparison of the plasma levels of 50% enantiomeric excess (S75/R25) 0.5%
      bupivacaine combined with 1:200,000 epinephrine between the parasacral and
      infragluteal sciatic nerve blocks.
AB  - BACKGROUND AND OBJECTIVES: Local anesthetics (LA) are safe drugs when the proper
      dose and localization are used. The rate of absorption of the local anesthetic
      depends on its mass and blood flow at the site of the injection. The objective of
      this study was to analyze the plasma concentration of 50% enantiomeric excess
      (S75R25) 0.5% bupivacaine combined with 1:200,000 epinephrine in the parasacral
      (PS) and infragluteal (IG) sciatic nerve block (SNB). METHODS: Twenty-eight
      patients scheduled for ankle and foot surgeries were randomly divided into two
      groups in this prospective study. In Group 1, SNB was performed with IG
      neurostimulation, while in Group 2 the PS method was used. Both groups received
      30 mL of 0.5% bupivacaine (S75/R25) with 1:200,000 epinephrine. Arterial blood
      samples, 5 mL, were drawn at 0, 15, 30, 60, and 90 minutes after the
      administration of the LA. High-performance liquid chromatography was used to
      analyze the serum concentrations. Demographic data of both groups were compared
      using the Student t test for independent samples and Fisher's Exact test.
      Bifactorial Analysis of Variance for repeated samples was used for the data
      concerning the plasma concentrations. RESULTS: Groups 1 and 2 showed no
      significant demographic differences. The maximal concentration (Cmax) in Group 1
      (308 +/- 91 ng.mL(-1)) was obtained in samples number 5 (90 minutes), while in
      Group 2 (425 +/- 280 ng.mL(-1)) it was obtained in samples number 2 (15 minutes).
      Cases of systemic toxicity were not observed. CONCLUSIONS: Cmax of 0.5 %
      bupivacaine (S75/R25) with 1:200,000 in the parasacral approach was higher when
      compared with the infragluteal SNB.

PMID- 19378581
TI  - Evaluation of hemodynamic variations during anesthetic induction in treated
      hypertensive patients.
AB  - BACKGROUND AND OBJECTIVES: Due to the high prevalence of hypertension, the
      increase in life expectancy, and improvement of diagnostic methods and surgical
      techniques, this comorbidity will be increasingly more common in surgical
      patients. The objective of this study was to evaluate the behavior of the
      hemodynamic variables during anesthetic induction in treated hypertensive
      patients. METHODS: This is an observational study on the behavior of hemodynamic
      parameters (systolic blood pressure, diastolic blood pressure, and heart rate)
      during the anesthetic induction of hypertensive and normotensive patients
      scheduled for elective surgeries under general anesthesia, at four moments:
      preparation (MP), drug (MD), laryngoscopy/intubation (ML), and 5 minutes after
      laryngoscopy/intubation (ML5). RESULTS: The sample was composed of 128 patients
      divided into two groups: hypertensive (GH) and normotensive (GN). Diastolic blood
      pressure was reduced at MD in both groups, with a smaller percentage reduction in
      GH (18.3 +/- 14.0% versus 23.0 +/- 11.4%, p = 0.04). There was an increase in SBP
      and DBP at ML in both groups, with smaller percentage reductions in GH (8.2 +/-
      16.3% versus 18.2 +/- 21.2%, p < 0.01; 8.6 +/- 20.2% versus 25.0 +/- 27.9%, p <
      0.01, respectively for DBP and SBP). As for ML5, HR, SBP and DBP did not show
      significant differences between both groups. CONCLUSIONS: Hypertensive patients
      under treatment and with controlled blood pressure levels demonstrated greater
      hemodynamic stability during anesthetic induction.

PMID- 19378582
TI  - Preoperative intravenous clonidine in the surgical treatment of cataract:
      evaluation of the clinical benefits.
AB  - BACKGROUND AND OBJECTIVES: Clonidine has been used in anesthesia for its sedative
      and analgesic properties, and to achieve greater hemodynamic stability with
      reduction in intra-ocular pressure. This study evaluated the clinical effects of
      intravenous clonidine (2.5 microg.kg(-1)) on the intra-ocular pressure (IOP),
      hemodynamic parameters, and post-anesthetic recovery in the surgical treatment of
      cataract. METHODS: This is a randomized, double-blind, placebo-controlled study
      that included patients undergoing cataract surgery under peribulbar block. After
      placement of monitoring devices, baseline (M0) values of IOP, mean arterial
      pressure (MAP), heart rate (HR), SpO2, and the degree of sedation (Ramsay) were
      determined. Afterwards, placebo (Group P) or clonidine (Group C) was administered
      intravenously. After 30 minutes, at Moment 1 (M1), measurements were repeated,
      and once again at the end of the surgery, at Moment 2 (M2). RESULTS: The change
      in IOP between M0 and M1 was different for both groups, 14.5% in Group C and
      5.25% in Group P (p = 0.01), and the means remained reduced until M2. Mean
      arterial pressure in Group C showed a 17% reduction from M0 to M1 and increased
      3.5% in Group P (p < 0.001) and in Group C it showed a recovery at M2 (p = 0.17).
      The heart rate decreased 6.4% in Group C and 1% in Group P (p = 0.1) from M0 to
      M1. There was a greater sedation in Group C when compared with Group P (p <
      0.001) but there was no cases of respiratory depression. The relative risk of
      intraoperative hypertension was 0.657 (CI 95% 0.517 to 0.835) in Group C, p <
      0.01. Differences in the incidence of tachycardia, hypoxemia, hypotension, and
      increased hospital staying were not observed between both groups. CONCLUSIONS:
      Clonidine, under the conditions of the present study, showed to be a safe drug
      and decreased IOP and the intraoperative risk of hypertension without delaying
      hospital discharge.

PMID- 19378584
TI  - Standardization of anesthesia in swine for experimental cardiovascular surgeries.
AB  - BACKGROUND AND OBJECTIVES: Although dogs are the animals used more often in
      Experimental Surgeries, the use of sheep, bovine, and swine as models for
      scientific experiments has been growing. Thus, further learning on the treatment
      and basic standardization of more complex surgeries in swine are necessary. The
      objective of this study was to evaluate sedation and analgesia, obtained by the
      intramuscular administration of midazolam and ketamine, and local anesthetics
      with 2% lidocaine without vasoconstrictor, in tracheostomy and dissection of
      femoral artery and vein. METHODS: The heart rate and corneal-palpebral reflex
      were evaluated at the beginning of sedation, during the surgical procedures, and
      at the end of those procedures. Eight Large White swine, without prior treatment,
      weighing 35 to 42 kg were provided by local farms. They received intramuscular
      injections of 22 mg.kg of ketamine and 0.3 mg.kg(-1) of midazolam. RESULTS: The
      anesthetic approach on those animals, who present both difficult intubation and
      access to deep vessels, proved to be safe for sedation and analgesia by the
      method chosen: intramuscular administration. CONCLUSIONS: An adequate plane of
      anesthesia for the proposed procedure was achieved.

PMID- 19378583
TI  - Thoracic epidural block performed safely in anesthetized patients. A study of a
      series of cases.
AB  - BACKGROUND AND OBJECTIVES: The development of paraplegia following the insertion
      of epidural catheter in anesthetized patients raised questions by some authors
      about the procedure, even without the confirmation that the lesion occurred
      because the patient was anesthetized. For this reason, we designed this study,
      with the objective to evaluate the frequency of neurological complications and
      development of sequelae after thoracic epidural block in patients under general
      anesthesia. METHODS: Patients undergoing thoracic surgeries from 02/16/2004 to
      05/30/2006 participated in the study. After monitoring vital signs and the
      installation of general anesthesia, patients were placed in lateral decubitus for
      simple or continuous thoracic epidural block. Intercurrences, complications, and
      technical difficulties were recorded on a special form. Patients were followed
      postoperatively to detect the development of any signs and symptoms of
      neurological dysfunction. RESULTS: One hundred and thirteen patients were
      evaluated and the thoracic epidural catheter was placed in 108 patients. The
      puncture was considered traumatic, i.e., bleeding at the puncture site and
      multiple punctures, in 45 patients. Accidental perforation of the dura-mater
      occurred in two patients. In the immediate postoperative period, a patient
      complained of tingling in the lower limbs, another patient developed numbness in
      an upper limb, which resolved after the catheter was removed. Both patients had a
      single puncture. The other patients did not develop any signs or symptoms of
      neurologic changes. CONCLUSIONS: The cases studied here did not develop any
      neurologic complications. When performed judiciously and with specific care,
      thoracic epidural block can be safely done in the anesthetized patient.

PMID- 19378585
TI  - Local effect of tramadol on formalin evoked flinching behavior in rats.
AB  - BACKGROUND AND OBJECTIVES: Tramadol hydrochloride is known as a centrally acting
      analgesic drug, used for the treatment of moderate to severe pain. A local
      analgesic effect has been demonstrated, but its mechanism of action remains
      unclear. METHODS: In this study, we examined the effect of local, systemic and
      nerve block tramadol on the nociceptive flinching behavior elicited by injection
      of 50 microL of 1% formalin into the dorsal region of hind paw of rats.
      Nociceptive flinching behavior was observed for 60 minutes. RESULTS: Local
      tramadol in higher concentrations (2.5 and 5 mg) almost eliminated flinching
      behavior during the entire test. Systemic and neural block tramadol did not
      affect flinching behavior in phase I and partially decreased it in phase II.
      CONCLUSIONS: Tramadol presented a local analgesic effect in formalin nociceptive
      flinching behavior that is different from its central analgesic effect. This
      analgesic effect, in this model, seems not to be linked to a local anesthetic
      like effect.

PMID- 19378586
TI  - Neuropathic pain after epidural needle trauma.
AB  - BACKGROUND AND OBJECTIVES: Neurologic complications secondary to epidural block
      are uncommon. Direct mechanical trauma to nerve roots may cause neuropathic pain
      that, usually, has a favorable evolution; however, it is a potentially severe
      complication that can evolve into a chronic disorder. The objective of this study
      was to discuss acute traumatic neuropathic pain and, especially, its treatment.
      CASE REPORT: A male patient was admitted for surgical treatment of
      gastroesophageal reflux via laparoscopy and scheduled to be discharged on the
      first postoperative (PO) day. He underwent epidural block associated with general
      anesthesia. During the localization of the epidural space, the patient complained
      of severe pain in the left lower limb. The needle was repositioned and the
      epidural space was located. In the PO, the patient developed allodynia and
      hyperesthesia. Neuropathic pain was diagnosed. Treatment included antidepressant,
      anticonvulsant, corticosteroids, tramadol, and vitamin B complex. On the 28th PO
      the patient was asymptomatic and presented a normal physical exam, being
      discharged from the hospital. CONCLUSIONS: The patient presented a favorable
      evolution with the treatment instituted. Early diagnosis and treatment can avoid
      irreversible lesions, change the prognosis, and avoid social and medical-legal
      consequences.

PMID- 19378587
TI  - Subdural hematoma after inadvertent dura mater puncture. Case report.
AB  - BACKGROUND AND OBJECTIVES: Post-dural puncture headache is a well-known
      complication of epidural and subarachnoid blockades and the blood patch is the
      treatment used more often. In most patients, the blood patch relieves the
      headache completely, but for the remaining there is no improvement or only
      partial relief of the symptom. In those cases, it is prudent to look for other
      differential diagnosis, such as subdural hematoma or pneumoencephalus. In those
      situations, imaging exams are extremely useful. The objective of this report was
      to present the case of a patient who developed subdural hematoma after accidental
      puncture of the dura mater during epidural block. CASE REPORT A 47-year old male
      patient, 147 kg, 1.90 m, physical status ASA II, was admitted for abdominal
      dermolipectomy after undergoing gastroplasty. The dura mater was accidentally
      punctured during the epidural block. The patient developed postdural puncture
      headache treated with an epidural blood patch, with partial improvement of his
      symptoms. However, it was followed by worsening of the headache and an MRI showed
      the presence of an intracranial subdural hematoma, which was treated clinically
      The patient evolved with progressive improvement of the symptom and full recovery
      after 30 days. CONCLUSIONS: Subdural hematoma is a rare, but severe, complication
      of dura mater puncture. It is difficult to diagnose, but it should always be
      remembered when post-dural puncture headache shows no resolution or even worsens
      after an epidural blood patch. An imaging exam is fundamental for the diagnosis
      of this rare complication.

PMID- 19378588
TI  - Negative-pressure pulmonary edema after transsphenoidal hypophysectomy. Case
      report.
AB  - BACKGROUND AND OBJECTIVES: Negative-pressure pulmonary edema (NPPE) is a rare
      complication that evolves rapidly after acute or chronic obstruction of the
      airways. The objective of this report was to present a case of NPPE after upper
      airways obstruction in a patient with acromegaly who underwent transsphenoidal
      hypophysectomy. CASE REPORT: A 48 years old male patient, weighing 80 kg,
      physical status ASA III, with a tumor in the hypophysis, hypertension, and
      acromegaly, underwent transsphenoidal hypophysectomy under general balanced
      anesthesia. The surgery proceeded without intercurrences. The patient was
      extubated while in a superficial anesthetic plane. He developed difficulty
      breathing, retraction of the abdominal wall, severe hypoxemia (SpO2 30%),
      unconsciousness, and cardiac arrhythmia (PVCs and bradycardia). Positive-pressure
      ventilation with a face mask and oropharyngeal cannula was ineffective. The
      patient was intubated and, at this moment, there were bilateral pulmonary rales
      and frothy pinkish secretion inside the tracheal tube, compatible with NPPE. The
      patient was transferred to the ICU and remained on mechanical ventilation for 96
      hours. He was discharged to the regular ward on the 5th postoperative day without
      neurological sequelae. CONCLUSION: Negative-pressure pulmonary edema may occur in
      the immediate postoperative period of transsphenoidal hypophysectomy. Immediate
      diagnosis and treatment are essential for early resolution of the process and to
      decrease morbidity.

PMID- 19378589
TI  - Amniotic fluid embolism during vaginal delivery under analgesia. Case report.
AB  - BACKGROUND AND OBJECTIVES: Amniotic fluid embolism is a rare occurrence; it has a
      sudden onset and high morbidity. The objective of this report was to present a
      case of amniotic fluid embolism in a primipara undergoing analgesia for vaginal
      delivery. CASE REPORT This is a 38-year old pregnant woman with amniotic sac
      ruptured, cervix with 5-cm dilation, complaining of severe pain; the patient was
      agitated, diaphoretic, and with tachysystoly. After venipuncture, Ringer's
      lactate with 5 IU of oxytocin was infused slowly, blood pressure (BP) 110 x 70
      mmHg, heart rate (HR) 115 bpm with sinus rhythm, and SpO2 98%. It was decided to
      use a combined technique: 2.5 mg of heavy bupivacaine and 20 microg of fentanyl
      were administered in the subarachnoid space and a catheter was inserted into the
      epidural space. Twenty minutes after the institution of analgesia, the patient
      complained of sudden onset of severe pruritus, she was agitated, with nausea and
      vomiting, pale, HR 160 bpm, tachypneic, SpO2 80%, and BP could not be detected.
      Normal saline (500 mL) associated with hydrocortisone, ephedrine (50 mg), and
      oxygen with a face mask at 10 L.min(-1) were administered. At that moment, she
      presented BP 60 x 30 mmHg, HR 150 bpm, and SpO2 92%. Since BP tended to decrease,
      a total of 7 mg of metaraminol were administered divided in several doses. After
      vaginal delivety the patient was transferred to the ICU with BP90 x 60 mmHg, HR
      110, and tachypnea. Two hours later, she developed bleeding and hypotension;
      disseminated intravascular coagulation (DIC) was diagnosed and the patient
      treated with crystalloid solutions, packed red blood cells and fresh frozen
      plasma. She was discharged from the ICU in the 3rd postoperative day (PO).
      CONCLUSIONS: Due to the dramatic presentation, severity, and fast installation of
      the symptoms, the speed and objectivity of the measures instituted to maintain
      vital signs are fundamental and decisive for survival of pregnant patients. We
      alert for the importance of monitoring during labor analgesia.

PMID- 19378590
TI  - Ultrasound-guided central venous puncture in an obese patient with cervical
      adenomegaly.
AB  - BACKGROUND AND OBJECTIVES: Classical central venous techniques are based on
      superficial anatomical references and the knowledge of the vascular anatomy of
      the area to be punctured. The ultrasound allows direct vision of vascular and
      perivascular structures, and the needle during the procedure. The objective of
      this report was to describe an ultrasound-guided central venous catheter
      placement in an obese patient with adenomegaly. CASE REPORT: This is a 28 years
      old white male patient, with 1.70 m, weighing 120 kg, with the diagnosis of
      nodular sclerosis Hodgkin's lymphoma. An ultrasound-guided internal jugular vein
      catheter placement was requested to the Anesthesiology Department of the Hospital
      Governador Celso Ramos due to the presence of a supraclavicular node that would
      hinder the anatomical reference for the puncture in an obese patient. After
      obtaining the best image, the left internal jugular vein was punctured and a
      triple lumen catheter was introduced. It was necessary only a single puncture and
      the catheter was easily introduced; no complications developed during the
      procedure.

PMID- 19378591
TI  - Eulogy to August Karl Gustav Bier on the 100th anniversary of intravenous
      regional block and the 110th anniversary of the spinal block.
AB  - BACKGROUND AND OBJECTIVES: August Karl Gustav Bier introduced two important
      techniques in regional block: intravenous regional block and subarachnoid block,
      widely used nowadays. Since the first one celebrates its 100th anniversary and
      the second its 110th anniversary, it is only fair that we pay homage to this
      extraordinary physician who created them. CONTENTS: This report describes his
      family, school, academic course, and medical residency data, professional and
      university activities, personality, retirement, and death of A. K. G. Bier. It
      describes his countless contributions to Medicine and to Anesthesiology in
      particular. It discusses his research on intravenous regional block, many of them
      still valid nowadays or not completely explained. It mentions his initial studies
      and the controversies on his role in the creation of spinal block. It tells the
      experiences he had in both World Wars. It also mentions the great contributions
      of Bier to culture, sports, physical education and, especially, to ecology when
      he created the famous Sauen Forest. Finally, the well deserved honors he received
      in his home country and in other countries are mentioned. CONCLUSIONS: A. K. G.
      Bier created and introduced two notable and still current methods of regional
      blocks in Anesthesiology and was a great defender of the preservation of the
      environment. Therefore, since this year we celebrate the 100th anniversary of
      intravenous regional block, his biography deserves to be told as a tribute to
      this important German physician.

PMID- 19378592
TI  - Remifentanil can reduce the diameter of the bowel.

PMID- 19378593
TI  - Topical anesthesia associated with Phacoemulsification. Experience with 312
      patients.

PMID- 19378594
TI  - Intraoperative pulmonary barotrauma during ophthalmologic surgery. Case report.

PMID- 19378596
TI  - 'Nothing off the table' for supply chain.

PMID- 19378595
TI  - WHO surgical safety checklist linked to fewer deaths, complications.

PMID- 19378597
TI  - New no-incision weight-loss surgery.

PMID- 19378598
TI  - Set the clock for OR on-time starts.

PMID- 19378599
TI  - Are staff using compression hose correctly?

PMID- 19378600
TI  - Closing the revolving door for OR staff.

PMID- 19378602
TI  - Is your OR prepared for a natural disaster?

PMID- 19378601
TI  - Tips for taming the OR chargemaster.

PMID- 19378603
TI  - Building bridges between SPD and OR.

PMID- 19378604
TI  - ASCs question how to meet CMS rules.

PMID- 19378605
TI  - Ten tips to improve your ASC's coding.

PMID- 19378606
TI  - Why work with a financial professional?

PMID- 19378607
TI  - To provide "free" dental care to staff, family, and friends...or not?

PMID- 19378608
TI  - Orthodontic camouflaging of skeletal malocclusions: a clinical perspective.

PMID- 19378609
TI  - Revisiting the importance of the neck exam.

PMID- 19378610
TI  - Complex interdisciplinary treatment: two case reports.

PMID- 19378611
TI  - A clinico-pathologic correlation.

PMID- 19378612
TI  - Incidental finding on dental radiographs: odontoma.

PMID- 19378613
TI  - Minocycline-induced staining of the oral cavity.

PMID- 19378614
TI  - It's a "small" world after all.

PMID- 19378615
TI  - Chlorhexidine gluconate mouthwashes as a surfactant for addition-reaction
      silicone impressions.
AB  - Addition-reaction silicone impression (PVS) materials are hydrophobic.
      Hydrophobicity of the impression material may interfere with the wetting of the
      tooth, resulting in void formation. The study investigates whether conditioning
      teeth with Chlorhexidine-gluconate based mouthwashes can reduce the
      hydrophobicity and the number of voids on PVS impressions. Impression material
      contact angle specimens on bovine tooth surfaces were measured using a Reflex
      Microscope. PVS impressions (President) were made of untreated bovine teeth in
      three groups (1, 2 and 3) and fourth group used Impregum polyether impression
      material: Group I was used as a control group, and original and mint flavoured
      Corsodyl (Chlorhexidine) mouthwashes were used as clinical surfactants in Groups
      2 and 3, respectively. Contact angle readings were recorded on each side of every
      impression in each of the four groups and compared by an analysis of variance. In
      the second part of the study, the numbers of air voids on impression surfaces
      were visually recorded. The proportions of air voids in the groups were compared
      using a Chi-squared test. The mean angle for Group 3 with mint flavoured Corsodyl
      mouthwash was significantly smaller than that of any of the other groups (P <
      0.05). The only statistically significant (P < 0.01) comparisons of the
      proportions of air voids were between Group 4 and each of the other experimental
      groups, with the percentage of voids being significantly greater in Group 4.
      Although Corsodyl mint significantly reduced the mean contact angle it did not
      significantly reduce the percentage of voids on impression surfaces.

PMID- 19378616
TI  - Comparison of the effect of ovariectomy on bone mass in dentate and edentulous
      mandibles of adult rats.
AB  - We investigated the effect of ovariectomy (OVX) on bone changes in the edentulous
      and dentate mandibles and compared these to changes in tibiae and femorae using
      dual energy x-ray absorptiometry (DEXA) and histomorphometric measurements. One
      hundred and fifteen female rats had their molars and the incisor on one side of
      the mandible extracted at six months of age and allowed to heal for 4 months. At
      10 months of age, animals were divided into an experimental group, which
      underwent bilateral ovariectomy, and a control group of intact animals. Sixteen
      OVX and sixteen control animals were sacrificed at 6-weeks, and at 6- and 9
      months post-OVX. In addition 12 animals were sacrificed at the time of OVX to act
      as an internal control group. Bone mineral density measurements (BMD) using DEXA
      and bone volume measurements on undecalcified sections evaluated under
      backscattered electron microscopy were investigated in the edentulous and dentate
      mandibles as well as in tibiae and femorae. At 6-weeks post-OVX, there were no
      significant differences between the edentulous mandibles, dentate mandibles,
      tibiae and femorae of OVX and control groups. At 6 months post-OVX, BMD and
      cancellous bone volume were significantly decreased in the edentulous mandibles (
      15.9%; -21.8%), proximal tibiae (-15.6%; -38.5%) and proximalfemorae (-9.7%; 
      39.6%) of OVX group as compared to the control group. At 9 months post-OVX, BMD
      and cancellous bone volume were further decreased in the edentulous mandibles (
      17.2%; -24%), proximal tibiae (-16.1%; -58.9%) and proximal femorae (-10.3%; 
      49.9%) of the OVX group as compared to the control group. On the other hand, OVX
      had no effect on the BMD and cancellous bone volume of the dentate mandibles at 6
      weeks and at 6- and 9-months post-OVX. These results show that loss of bone mass
      in the edentulous mandible of OVX animals is similar to that occurring in the
      tibiae and femorae, while lack of a significant effect of OVX on bone mass in the
      dentate mandible suggests that functional loading related to biting force
      prevented bone loss in the dentate mandible.

PMID- 19378617
TI  - Resin-bonded cast splints for loosened abutment teeth to anchor a removable
      partial denture: a case report.
AB  - This case report describes a technique to stabilize loosened abutment teeth by
      seating resin-bonded cast splints with rest seats and surveyed guide planes to
      anchor a removable partial denture. This technique can achieve sufficient
      stability of the abutment teeth and proper support and bracing of the removable
      partial denture with minimal intervention.

PMID- 19378618
TI  - Computerised dental implant rehabilitation planning and execution following
      mandibular resection: a case report.
AB  - This paper discusses the merits of Computer Tomography (CT) based dental implant
      planning in the rehabilitation of patients following oral cancer This case report
      describes the process of prosthetic work-up, computerised implant planning,
      surgical treatment and successful prosthetic oral rehabilitation of a patient
      following segmental mandibulectomy and post-operative radiotherapy for intra
      osseous squamous cell carcinoma (SCC).

PMID- 19378619
TI  - A novel instrument to determine pulp proximity.
AB  - The aim was to determine whether extracted teeth could be used to test the
      Prepometer instrument, which indicates pulp proximity with green/amber/red light
      emitting diodes. Third molars were reduced to a plane in dentine and Prepometer
      readings made. Dentine was removed in 0.5 mm increments and readings made until
      only lights 9 or 10 (red) showed. The teeth were sectioned and the dentine
      thickness measured. Analysis permitted construction of a highly significant
      predictor-model (p < 0.01), the red/amber light boundary coinciding with a
      dentine thickness of 2.4 mm. The Prepometer was consistent in predicting pulp
      proximity but was more sensitive than specified.

PMID- 19378620
TI  - The prevalence of temporomandibular disorders among two different denture-wearing
      populations.
AB  - AIM: The aim of this clinicostatistical study was to profile the complete denture
      wearers of two different populations, to determine any possible relationship
      between the prevalence of temporomandibular disorders (TMDs) and factors involved
      in complete denture wearing and to compare this prevalence between the groups.
      MATERIALS AND METHODS: Denture wearers who attended the clinics of the Dental
      School and Hospital, University of Bristol, U.K. (group A) and the Dental School,
      University of Athens, Greece (group B), were examined. An approximately equal
      number of patients; 115 for group A and 136 for group B, were selected. The
      examination included: (a) a history record with reference to sex, age, years of
      complete denture experience, sets of dentures used, age of the current dentures,
      time period of every day denture wearing, any difficulties on opening the mouth,
      and/or pain at the temporomandibular joint (TMJ) region and (b) a
      craniomandibular clinical examination in relation to midline deviation, pain and
      sounds from the joints, pain in the related muscles and inspection of the
      vertical dimension of occlusion. Data collected were analyzed using the chi
      square test. RESULTS: Denture wearers of group A were older, presented with
      greater experience in complete denture wearing, used more sets of dentures, most
      wore dentures exhibiting decreased vertical dimension of occlusion and wore their
      dentures only in the day time. The TMDs prevalence was not statistically
      significantly different between A and B groups (34.8% and 41.2% respectively). In
      group B the TMDs prevalence was greater in females. There was a decreasing TMDs
      prevalence with increasing age. Neither of the groups showed significant TMDs
      prevalence in relation to the denture experience, the number of dentures used,
      the age of the present denture nor the vertical dimension of occlusion. Group B
      showed a decreasing TMDs prevalence in relation to continuous denture wearing.
      CONCLUSIONS: This clinicostatistical study showed that two different population
      groups of complete denture wearers who presented with different profiles have
      similar prevalence of TMDs.

PMID- 19378621
TI  - Investigation of the effect of a proprietary dental waterline disinfectant on
      shear bond strengths of Panavia 21 to enamel and dentine.
AB  - This study investigated the effect of 'Alpron mint', a dental unit waterline
      disinfectant, on shear bond strengths between 'Panavia 21' resin based cement and
      tooth tissue. Eighty-eight human premolar tooth specimens were prepared in either
      enamel (N=44) or dentine (N=44). Half the specimens within each group were
      irrigated with an Alpron mint solution and the other half with distilled water
      (control) prior to application of Panavia 21 resin luting cement. There was no
      significant difference in shear bond strengths for both enamel and dentine with
      Alpron mint irrigation compared with distilled water (P = 0.245).

PMID- 19378622
TI  - The nurse as a volunteer.

PMID- 19378623
TI  - The gift that keeps on giving.

PMID- 19378624
TI  - Temporary work reassignment for registered nurses.

PMID- 19378625
TI  - Predictors of a health-promoting lifestyle and behaviors among low-income African
      American mothers and white mothers of chronically ill children.
AB  - This study used Health Self-Empowerment (HSE) Theory as a framework for examining
      the predictors of engagement in both a health-promoting lifestyle and individual
      health-promoting behaviors among low-income African American mothers and non
      Hispanic white mothers (N = 96), each of whom is the primary caregiver for a
      chronically ill adolescent. The individual health-promoting behaviors
      investigated are eating a healthy diet, exercising consistently, stress
      management practices, and health responsibility behaviors. The examined HSE
      Theory-based predictor variables were health self-efficacy, active coping, health
      motivation, and health self-praise. Multiple regression analyses revealed that
      these predictor variables together accounted for a significant amount of variance
      (67%) in level of engagement in a health-promoting lifestyle. Additionally,
      active coping, health self-praise, health self-efficacy, and health motivation
      were significant individual predictors of 1 or more individual health-promoting
      behaviors. Findings from this study suggest that further research should be
      conducted to assess the usefulness of HSE Theory in predicting level of
      engagement in health-promoting behaviors and to examine the effectiveness of HSE
      Theory-based interventions for increasing health-promoting behaviors among women
      similar to those in this study. The findings also suggest that health care
      providers should promote active coping, health self-praise, health self-efficacy,
      and health motivation to increase health-promoting behaviors among patients who
      are similar to those in this study.

PMID- 19378626
TI  - Racial/ethnic disparity in kidney transplantation outcomes: influence of donor
      and recipient characteristics.
AB  - OBJECTIVE: The purpose of this study was to evaluate the basis for the
      racial/ethnic disparity in kidney allograft survival. METHODS: We conducted a
      retrospective study of 2130 patients who underwent kidney transplantation between
      January 1995 and December 2003. Patient and graft survivals were compared using
      Kaplan-Meier analysis. RESULTS: Black recipients were more likely than white
      recipients to have hepatitis C infection (24.6% vs 7.1%), current tobacco use
      (21.2% vs 13.1%), previous alcohol use (22.6% vs 9.7%), and past illicit drug use
      (13.6% vs 3.9%). Current employment was less common among blacks. Additionally,
      black recipients were more likely to have a prior kidney transplant (16.7% vs
      11.0%) and to have a cadaver kidney donor (74% vs 56.5%). The 5-year allograft
      survival rate was 72% for whites and 59% for blacks (p < .01). Previous kidney
      transplantation, cadaveric donor, donor age, recipient employment status, and
      recipient tobacco use were associated with allograft survival in a Cox
      proportional hazard model. CONCLUSIONS: Graft survival rate in black kidney
      transplant recipients is significantly lower than whites, and this disparity can
      be partially explained by the low rate of live donors and a higher previous
      transplantation rate in blacks.

PMID- 19378627
TI  - Cultural competency in medical education: demographic differences associated with
      medical student communication styles and clinical clerkship feedback.
AB  - PURPOSE: We tested the significance of associations among students' demographics,
      communication styles, and feedback received during clerkships. METHODS: US
      medical students who completed at least one required clinical clerkship were
      invited between April and July 2006 to complete an anonymous, online survey
      inquiring about demographics, communication styles (assertiveness and reticence),
      feedback (positive and negative), and clerkship grades. The effects of self
      identified race/ethnicity, gender, and generation (immigrant, first- or second
      generation American) and their 2-way interactions on assertiveness, reticence,
      total positive and total negative feedback comments were tested using factorial
      analysis of covariance, controlling for age, clerkship grades, and mother's and
      father's education; pairwise comparisons used simple contrasts. Two-sided P
      values < .05 were considered significant. RESULTS: Medical students from 105
      schools responded (N = 2395: 55% women; 57% white). Men reported more
      assertiveness than women (P = .001). Reticence (P < .001) and total positive
      comments (P = .006) differed by race/ethnicity; in pairwise contrasts, black,
      East Asian, and Native American/ Alaskan students reported greater reticence than
      white students (P < .001), and white students reported receiving more positive
      comments than black, and South and East Asian students. Race/ethnicity-by
      generation (P = .022) and gender-by-generation (P = .025) interaction effects
      were observed for total negative comments; white first-generation Americans
      reported receiving the fewest and male immigrants reported receiving the most
      negative comments. CONCLUSIONS: Demographic differences in students'
      communication styles and feedback they received highlight a need for cultural
      competency training to improve medical student-teacher interactions, analogous to
      training currently advocated to improve physician-patient interactions.

PMID- 19378628
TI  - The relationship between drivers and policy in the implementation of cultural
      competency training in health care.
AB  - In recent years, cultural competence has appeared on the agendas of the medical
      profession as well as other health care providers. Through semistructured
      interviews with staff at different types of health care institutions, we explored
      the motivation for and barriers against the implementation of cultural competence
      training. The findings show that while some progress has been made, there is
      still work to be done in making cultural competency an integral part of the
      organizational fabric of health care. National organizations need to consider
      their leadership role in helping health care organizations translate broad
      statements of cultural competence into meaningful action.

PMID- 19378629
TI  - Age-related macular degeneration: a guide for the primary care physician.
AB  - Age-related macular degeneration (AMD) is the leading cause of visual loss in
      Americans over the age of 50 years. AMD often results in profound disability due
      to the disease destroying the macula, the part of the retina responsible for
      central visual acuity and color vision. Risk factors for AMD include age greater
      than 50, female gender, Caucasian race, cigarette smoking, and family history of
      AMD. African Americans and other racial or ethnic groups can be affected by AMD.
      Although there is no cure for AMD, early diagnosis and treatment may slow disease
      progression and minimize irreversible visual dysfunction. Individuals suffering
      from central vision loss from AMD often retain peripheral vision. These affected
      individuals can benefit from low vision therapy, visual rehabilitation, or both
      to maintain or enhance activities of daily living.

PMID- 19378630
TI  - Physical and mental health in adults hospitalized with sickle cell disease:
      impact on resource use.
AB  - BACKGROUND: It is commonly perceived that patients with sickle cell disease have
      increased hospital length of stay (LOS) because of mental health issues,
      including depression and drug-seeking behavior. However, the effect of mental and
      physical functional status on acute care resource use is unknown. OBJECTIVE: To
      assess Short Form (SF)-12 physical and mental health scores in adults with sickle
      cell disease and their impact on hospital LOS and costs. DESIGN: We identified
      145 adults with sickle cell disease admitted to the general medicine ward at the
      University of Chicago Medical Center between July 1997 and June 2003. Seventy
      nine patients (54%), with a total of 103 admissions, completed the SF-12 for at
      least one admission. Administrative data were used to obtain demographic
      information, LOS, and costs. Multivariate regression was used to measure the
      association between SF-12 physical and mental composite scores (by quartile), and
      LOS and costs. RESULTS: Twenty-five percent of patients accounted for nearly 80%
      of total hospital days and costs. The mean SF-12 physical score was 40 (SD, 12),
      and mental score 49 (SD, 12). Adjusted for age, gender, race, and comorbidities,
      admissions in the lowest quartile of the SF-12 physical composite score had an
      average LOS of 7.11 days and costs of $9060, compared to 4.6 days and $5520 in
      the highest quartile (p < .03, < .05). The SF-12 mental compositive score was not
      significantly associated with LOS or costs. CONCLUSIONS: Poor physical function
      rather than poor mental function independently predicts greater use of acute
      health care resources in adults with sickle cell disease.

PMID- 19378631
TI  - Osteoporosis awareness protocol for patients with fragility fractures.
AB  - OBJECTIVE: To develop and implement a protocol that improves recognition of
      osteoporosis in patients with fragility fractures. METHODS: The awareness
      protocol included 6 meetings with the clinical staff of the emergency department
      (ED) and the orthopedic department to discuss osteoporosis awareness, a poster
      placed in the ED triage and orthopedic residents' rooms, monthly verbal awareness
      reminders, and distribution of pocket-sized poster copies to the residents.
      RESULTS: Two hundred ninety-one patients with fractures were admitted to Howard
      University Hospital from June 2005 - December 2005. Fractures were evident in 11%
      (n = 32). All were admitted from the ED. Of the patients with fractures, 81% were
      African American--62.5% were women with a mean age of 73.3 +/- 15.8 years; the
      mean age of the men, 59.3 +/- 14.9 years. The orthopedists requested an endocrine
      consult for 8 patients. Osteoporosis was evident in 25% of the fracture patients
      (n = 8). One of these patients was diagnosed on the basis of risk factors, thus
      22% were diagnosed on the basis of dual-energy x-ray absorptiometry and
      pathological findings. As compared with a prior study, this is a significant
      increase (13%, p = .02) in the diagnostic rate at this institution.
      Bisphosphonates were prescribed for 3 of the 32 patients (9%) prior to discharge.
      CONCLUSION: This pilot study presents an easy-to-execute awareness protocol that
      significantly improved the diagnosis of osteoporosis in a predominantly African
      American population with fractures. The diagnosis of osteoporosis may be enhanced
      by cooperative efforts among ED, orthopedics, endocrinology, and other
      disciplines.

PMID- 19378632
TI  - Fatty liver and hyperlipidemia in a cohort of HIV-positive Africans on highly
      active antiretroviral therapy.
AB  - AIM: To determine the prevalence of fatty liver and to assess its association
      with hyperlipidemia and other metabolic risk factors in HIV/AIDS patients on long
      term antiretroviral therapy. METHODS: A prospective cross-sectional study of 113
      adults attending an urban outpatient HIV clinic in Lagos, Nigeria. Demographic
      characteristics were obtained using interviewer administered questionnaires, and
      serum levels of fasting glucose, total cholesterol, high-density lipoprotein (HDL
      C) and low-density lipoprotein cholesterol (LDL-C), and alanine transaminase were
      determined. Ultrasound scan imaging was used to identify hepatic steatosis.
      RESULTS: One hundred thirteen subjects, mean age (SD), 38.7 (9.9) years on highly
      active antiretroviral therapy (HAART) therapy for 6 to 42 months were evaluated.
      Sixty-six (58.4%) were female and 47 (41.6) were male. Fifteen (13.3%) had
      hepatic steatosis. Total cholesterol > 200 mg/dL, LDL-C > 130 mg/dL, and fasting
      serum triglycerides > 150 mg/dL were seen in 28%, 24% and 35%, respectively. The
      presence of fatty liver was significantly associated with hepatomegaly (p = .03)
      and elevated LDL-C (p = .01). CONCLUSION: The prevalence of hepatic steatosis is
      lower than reported in Caucasian populations, but strongly associated with
      hepatomegaly and hyperlipidemia in subjects on long-term HAART. Early recognition
      of fatty liver and regular screening for lipid are warranted in Africans
      receiving long-term HAART.

PMID- 19378633
TI  - Stress of caring for children: the role of perceived racism.
AB  - PURPOSE: Regardless of race, most mothers experience stress related to concerns
      about their children. African American mothers may experience the additional
      stress of their child (ren) experiencing racism. We describe the stress that
      African American women have about their children experiencing racism. METHODS:
      The Telephone-Administered Perceived Racism Scale (TPRS) was administered to 476
      African American women ages 36 to 53 who were members of a prepaid health plan.
      The 8-item Concern for Children scale, 1 of the 5 TPRS scales, was completed by
      382 women and assessed the level of concern women have about their children
      experiencing racism. The responses ranged from "not at all concerned" to "very
      concerned." RESULTS: For 6 of the 8 items, more than 60% reported being "very
      concerned" for their children. Items of highest concern involved
      institutionalized racism with more than 70% reported being very concerned about
      their children being harmed or harassed by the police or getting stopped in a
      predominantly white neighborhood. Respondents were less concerned about their
      children being considered less attractive than their white counterparts and/or
      being excluded from social events, activities, or groups. Level of concern was
      not related to income or education. Unsurprisingly, respondents who reported high
      levels of perceived racism also reported greater concern for their child(ren).
      CONCLUSIONS: These findings highlight an additional stressor related to
      childrearing in a "race-conscious" society. Future research on stress and African
      American women's health should include this additional stressor.

PMID- 19378634
TI  - Disparities in influenza immunization among US adults.
AB  - In the United States, health disparities exist among ethnic minority groups, the
      uninsured, and those with other barriers to health care access. Health
      disparities exist for many diseases, but are especially pronounced for preventive
      health services and preventable diseases. Persons affected by disparities
      experience higher incidences of vaccine-preventable diseases, such as influenza,
      and are more likely to die from those diseases as well. Although influenza
      vaccines are relatively safe, inexpensive, and effective in reducing infection
      and disease complications, many groups in the United States do not yet benefit
      from this potentially lifesaving intervention. Possible explanations for
      disparities in influenza vaccination include: (1) barriers to access such as
      cost, insurance status, and language differences; (2) underestimation of personal
      risk and misunderstanding of vaccination risks; (3) mistrust toward the health
      care system. Proposed strategies to minimize these disparities include: (1)
      changes to health care system structural factors that serve as access barriers,
      (2) education to increase awareness and improve demand for vaccines, (3)
      involvement of community-based organizations to assess local needs and design
      responsive solutions.

PMID- 19378635
TI  - Cross-border purchase of medications and health care in a sample of residents of
      El Paso, Texas, and Ciudad Juarez, Mexico.
AB  - BACKGROUND: We examined data from a US-Mexico bi-national survey conducted among
      adult residents of El Paso, Texas, and Ciudad Juarez, Mexico, to assess frequency
      of purchase of medications and use of health care services across the border.
      METHODS: We analyzed questionnaire data from face-to-face interviews of 1000
      randomly selected adults on both sides of the border to assess prevalence and
      prevalence ratios using log binomial logistic regression analysis. RESULTS: One
      third of adult residents of El Paso and 5% of those in Ciudad Juarez reported
      crossing the border to purchase medications (P < .001). Lack of health insurance
      in the United States was associated with crossing the border to purchase
      medications. Nine percent and 7% of US residents traveled to Mexico seeking
      dental and medical care, respectively. Mexican nationals traveling to the United
      States to purchase medications or health care services were more likely to be
      uninsured and more-educated men. CONCLUSION: US residents of areas along the
      border in close proximity to Mexico often travel south to purchase medications.
      Other health care services are also utilized, although at lower rates. These
      patterns may be attributed to a number of barriers to health care in the United
      States.

PMID- 19378636
TI  - Quality of life before and after laparoscopic Heller procedures--a Caribbean
      perspective.
AB  - BACKGROUND: The aim of this study was to compare the symptoms and quality of life
      before and after laparoscopic Heller myotomy within a Caribbean population.
      METHOD: Sixteen patients who were treated by the same surgeon were polled. The
      procedure was laparoscopic Heller myotomy with or without concomitant
      fundoplication. A specifically constructed questionnaire that assessed
      symptomatology and the quality of life (via social and emotional functioning
      scores) was administered. RESULTS: The mean age of the patients was 38.4 years;
      11 were female and 5 were male. The mean preoperative duration of symptoms was
      5.5 years (range, 1-13). All patients complained of dysphagia (liquids and
      solids), odynophagia, and preoperative regurgitation. Follow-up was completed
      with a mean postoperative duration of 16.7 months. Overall, symptoms improved by
      an average of 71.2%; social and emotional functioning improved by an average of
      42.2% (p < .001). CONCLUSION: Laparoscopic Heller myotomy is extremely effective
      in improving the overall quality of life among achalasia patients within the
      Caribbean.

PMID- 19378637
TI  - Exploring the "legacy" of the Tuskegee Syphilis Study: a follow-up study from the
      Tuskegee Legacy Project.
AB  - The purpose of this follow-up 2003 3-City Tuskegee Legacy Project (TLP) Study was
      to validate or refute our prior findings from the 1999-2000 4 City TLP Study,
      which found no evidence to support the widely acknowledged "legacy" of the
      Tuskegee Syphilis Study (TSS), ie, that blacks are reluctant to participate in
      biomedical studies due to their knowledge of the TSS. The TLP Questionnaire was
      administered in this random-digit-dial telephone survey to a stratified random
      sample of 1162 black, white, and Puerto Rican Hispanic adults in 3 different US
      cities. The findings from this current 3-City TLP Study fail to support the
      widely acknowledged "legacy" of the TSS, as awareness of the TSS was not
      statistically associated with the willingness to participate in biomedical
      studies. These findings, being in complete agreement with our previous findings
      from our 1999-2000 4-City TLP, validate those prior findings.

PMID- 19378638
TI  - The Quigless Clinic: its impact on the lives of African Americans living in
      Tarboro, North Carolina, in the 1950s.
AB  - Dr Milton Douglas Quigless, a graduate of Meharry Medical College, arrived in
      Tarboro, North Carolina, in 1936 to practice medicine. For 10 years, he tried to
      obtain hospital privileges at the Edgecombe General Hospital, but segregation
      laws prevented him from performing surgery and admitting ill patients to this
      local facility. After years of frustration, Dr Quigless decided to establish his
      own hospital so that he could adequately care for his patients. In 1946, the
      doors of the Quigless Hospital-Clinic opened--the first hospital for blacks in
      Tarboro. As a noted family physician and distinguished community leader, Dr
      Quigless had an enormous impact on the lives of multiple generations of North
      Carolinians.

PMID- 19378639
TI  - A surgeon's and son's perspective on his father's career in medicine.

PMID- 19378640
TI  - Journal reading: a menu of keywords or a surprising feast.

PMID- 19378641
TI  - Introduction to the special section--gendered power in cultural contexts:
      capturing the lived experience of couples.

PMID- 19378642
TI  - Gendered power in cultural contexts: Part I. Immigrant couples.
AB  - Immigration is a world-wide phenomenon and practitioners are increasingly called
      on to work with issues related to it. The authors examine the experience of
      couples who are immigrants to the United States in regard to gender and power
      issues. Although the study limited participation to one religious group in order
      to hold that aspect of culture and gender attitudes constant, the experiences of
      these couples help to make visible the link between microlevel couple interaction
      and larger social processes. The results show how the couples manage a delicate
      balance between the push for gender change and avoiding too much conflict as male
      power is challenged.

PMID- 19378643
TI  - Gendered power in cultural contexts: Part II. Middle class African American
      heterosexual couples with young children.
AB  - When race and gender intersect, understanding gendered power may be complicated.
      The authors first describe the historical context that serves as important
      background for understanding gender and power in heterosexual African American
      relationships. Then they show how family solidarity in the face of social
      injustices often overrides gender equality as a goal for middle class African
      American couples with young children. The findings illustrate pragmatic equality
      within couple relationships and the willful suspension of gender roles for the
      well-being of the family as a whole. However, gendered power impacts couples in a
      variety of ways. Sometimes a woman's fear that the man might leave, for example,
      diminished her power in the relationship. Often a woman accommodated a man's
      greater power in the family because of her perception that he was often denied
      power in the larger society. Societal discrimination of women was less visible to
      couples. Implications for practice are provided.

PMID- 19378644
TI  - Gendered power in cultural contexts: Part III. Couple relationships in Iran.
AB  - Sometimes therapists assume that gender equality is not relevant when working
      with couples from traditional cultures. This study of couples in Iran suggests
      more complexity. The authors identify a variety of views and practices regarding
      equality between men and women in relationships. Some aspired to traditional
      roles; others attempted to create mutually supportive relationships. Yet others
      were somewhere in-between. This study helps identify important dimensions that
      may be overlooked when we define couple equality only by American standards or
      understand it only through a Western lens. The study provides insight into the
      dilemmas couples face when ideals of equality intersect with societal structures
      that maintain gendered power and offers suggestions for addressing gender when
      working with couples with traditional cultural backgrounds.

PMID- 19378645
TI  - Affective synchrony in dual- and single-smoker couples: further evidence of
      "symptom-system fit"?
AB  - Couples in which one or both partners smoked despite one of them having a heart
      or lung problem discussed a health-related disagreement before and during a
      period of laboratory smoking. Immediately afterwards, the partners in these 25
      couples used independent joysticks to recall their continuous emotional
      experience during the interaction while watching themselves on video. A couple
      level index of affective synchrony, reflecting correlated moment-to-moment change
      in the two partners' joystick ratings, tended to increase from baseline to
      smoking for 9 dual-smoker couples but decrease for 16 single-smoker couples.
      Results suggest that coregulation of shared emotional experience could be a
      factor in smoking persistence, particularly when both partners in a couple smoke.
      Relationship-focused interventions addressing this fit between symptom and system
      may help smokers achieve stable cessation.

PMID- 19378646
TI  - Multidimensional family therapy HIV/STD risk-reduction intervention: an
      integrative family-based model for drug-involved juvenile offenders.
AB  - Drug and juvenile justice involved youths show remarkably high rates of human
      immunodeficiency virus (HIV)/sexually transmitted disease (STD) risk behaviors.
      However, existing interventions aimed at reducing adolescent HIV risk behavior
      have rarely targeted these vulnerable young adolescents, and many approaches
      focus on individual-level change without attention to family or contextual
      influences. We describe a new, family-based HIV/ STD prevention model that embeds
      HIV/STD focused multifamily groups within an adolescent drug abuse and
      delinquency evidence-based treatment, Multidimensional Family Therapy (MDFT). The
      approach has been evaluated in a multisite randomized clinical trial with
      juvenile justice involved youths in the National Institute on Drug Abuse Criminal
      Justice Drug Abuse Treatment Studies (www.cjdats.org). Preliminary baseline to 6
      month outcomes are promising. We describe research on family risk and protective
      factors for adolescent problem behaviors, and offer a rationale for family-based
      approaches to reduce HIV/STD risk in this population. We describe the development
      and implementation of the Multidimensional Family Therapy HIV/STD risk-reduction
      intervention (MDFT-HIV/ STD) in terms of using multifamily groups and their
      integration in standard MDFT and also offers a clinical vignette. The potential
      significance of this empirically based intervention development work is high;
      MDFT-HIV/STD is the first model to address largely unmet HIV/STD prevention and
      sexual health needs of substance abusing juvenile offenders within the context of
      a family-oriented evidence-based intervention.

PMID- 19378647
TI  - Cultural, gender, and socioeconomic contexts in therapeutic and social policy
      work.
AB  - The contention of this paper is that the context of social and therapeutic
      problems is critical to their resolution, and that many of them stem from
      historical and structural injustice. It focuses on the contextual issues of
      cultural, gender, and socioeconomic equity as providing important insights into
      authentic notions of social inclusion and well-being, and encourages therapists,
      service providers, researchers, and policy makers to take responsibility to
      ensure that these injustices are addressed, and become part of the public
      discourse about the sources and solutions of endemic social problems. Critique
      and deconstruction of institutional power in our public, private, and voluntary
      services is encouraged in a manner that honors diversity and enables sensitive
      therapy, other forms of service delivery and policy making that genuinely reflect
      the range of cultural, gender, and socioeconomic experiences of citizens.

PMID- 19378648
TI  - Collaborative helping: a practice framework for family-centered services.
AB  - This article offers a framework for collaborative family-centered practice that
      can rein-vigorate our work with families who have not responded to more
      traditional approaches. Collaborative Helping is grounded in family-centered
      principles that include: striving for cultural curiosity, believing in
      resourcefulness, working in partnership, and making our work more accountable to
      the clients we serve. The article introduces collaborative inquiry as an
      organizing metaphor for clinical practice and offers a five-step practice
      framework with clinical illustrations and sample questions. The framework draws
      from appreciative inquiry, motivational interviewing, the signs of safety
      approach to child protection work, and solution-focused and narrative therapies.

PMID- 19378649
TI  - Relational drawings in couple therapy.
AB  - In couple therapy sessions, partners often get into long and drawn-out
      discussions, heavy with pain, resentment, and blame. It is vital for the
      therapist to avoid becoming entangled in these escalating interactions. In this
      article, as one way of avoiding these interactions, a protocol is proposed of
      using relational drawings in couple therapy for opening space for new stories.
      This approach is strongly rooted in extensive therapeutic experience, as well as
      in dialogical ideas. Not the content of the partners' imagery is central, but
      rather the dialogical exchange about the drawings. In particular, the focus of
      the therapist is on the partners' interactions, their hesitations and their
      surprises. Working in this way opens space for the partners to reflect on what
      they experience as crucial in their bond. The protocol is illustrated with two
      detailed case examples.

PMID- 19378650
TI  - Empathic family stress as a sign of family connectedness in Haitian immigrants.
AB  - Research on familial experiences has documented the important role of receiving
      family support, but has not examined the effects of providing such support.
      Empathic family stress refers to the stress that individuals experience in
      response to difficult life circumstances of family members. The current study
      took a first step in examining the empathic family stress of 134 Haitian
      immigrants. Results from hierarchical regressions indicate that empathic family
      stress is a significant predictor of depressive symptoms, but not acculturative
      stress, for Haitian immigrants. Findings from the study are examined from a
      strengths-based perspective, where empathic family stress is viewed as a sign of
      strong family connections among Haitian immigrants. Recommendations are provided
      for clinicians working with Haitian immigrants to help them experience empathic
      family stress in a healthy manner.

PMID- 19378651
TI  - Portuguese immigrant families: the impact of acculturation.
AB  - Portuguese immigrants to North America represent a large ethnic group with unique
      family therapy needs. The present study investigates acculturation and the family
      lives of Portuguese (Azorean) immigrants in Canada. Methods of analytic induction
      and constant comparison from grounded theory were used to examine transcripts of
      interviews with 21 Azorean immigrant women and 28 Azorean immigrant men. A model
      emerged wherein (a) immigration and acculturation act as stressors on the family
      unit, as described by the categories Process of Change and Family Relationships;
      (b) family members adopt generation- and gender-specific acculturative
      strategies, as illustrated by the categories Duas Culturas (Two Cultures) and
      Falando Portuges (Speaking Portuguese); and (c) as family members acculturate,
      discords arise and are resolved according to the cultural traits different
      members have adopted. The categories Discord Resolution and Preocupacao
      (Preoccupations) illustrate this last dynamic. Implications for family therapy
      with immigrant families include an indication for community-level interventions,
      emphasis on confidentiality, awareness of acculturation stress and different
      acculturative strategies within the family, and aiding the family in the
      negotiation and integration of a new bicultural reality.

PMID- 19378652
TI  - Comparison of performance and operation of side-by-side integrated fixed-film and
      conventional activated sludge processes at demonstration scale.
AB  - A full-scale demonstration of an integrated fixed-film activated sludge (IFFAS)
      process with floating carriers has been conducted in Ontario, Canada, since
      August 2003. In this study, data collected on-site from July 2005 to December
      2006 are analyzed and compared with the performance of a conventional activated
      sludge train operated in parallel. Both trains received similar loadings and
      maintained comparable mixed liquor concentrations; however, the IFFAS had 50%
      more biomass when the attached growth was considered. In the winter, the
      conventional train operated at the critical solids retention time (SRT) and had
      fluctuating partial nitrification. The IFFAS nitrified more consistently and had
      a doubled average capacity. In the summer, the suspended SRT was less limiting,
      and the benefit of IFFAS for nitrification was marginal. The lessons learned from
      the operational requirements and challenges of the IFFAS process (air flow,
      carrier management, and seasonal foaming) are discussed, and design
      recommendations are proposed for whole plant retrofit.

PMID- 19378653
TI  - Development of a low-cost wastewater treatment system for small-scale wineries.
AB  - A pilot-scale winery wastewater treatment system was developed to treat
      wastewater produced by a small winery (approximately 1200 metric tons of grapes
      crushed). The pilot system consisted of a sedimentation/aerobic process combined
      with a bioremediation wastewater cell planted with Juncus ingens. The main design
      specifications, detailed descriptions of the plant, and analysis of the influent
      and effluent characteristics (pH, electrical conductivity, total suspended
      solids, chemical oxygen demand [COD], etc.) are reported for each segment of the
      system. Over the study period, the mean winery wastewater flowrate was 3.5 m3/d
      at organic loads of 5000 to 14 000 mg-COD/L. The study measured average removal
      rates of 72% for COD and 65% for total organic carbon and dissolved carbon. The
      application of wastewater to the soil increased the soil salinity in the top 30
      cm, but remained stable below this. The system also seemed to be effective at
      neutralizing the pH of the acidic winery wastewater and at removing the
      phosphorus pool (65%) in the wastewater, whereas the levels of nitrogen and most
      of the cations increased in the treated effluent. The absorbing/adsorbing and
      degradation capacity of the soil of the wastewater bioremediation cell did not
      appear to be exhausted after one vintage. Juncus ingens appeared to grow
      moderately well, until the end of the vintage, when dieback began to occur. An
      infilling with organic matter of the surface soil layer under the root zone was
      observed, which reduced water infiltration and hence system treatment capacity.
      The data provide evidence that this is a potentially effective wastewater
      treatment approach for small wineries located in rural areas.

PMID- 19378654
TI  - Biological denitrification using corncobs as a carbon source and biofilm carrier.
AB  - In this research, agricultural waste--in particular, comcobs--was investigated
      for use as the sole carbon source and biofilm carrier to remove nitrate from
      wastewater in up-flow laboratory reactors. An artificial wastewater with a
      temperature range of 27 to 33 degrees C was used. Fast startup of the reactor and
      a high nitrate removal efficiency were observed. The highest denitrification rate
      of 0.203kg/(m3 x d) was achieved when flow rate and nitrate concentration were
      153 L/d and 25.3 mgN/L, respectively. The accumulation of nitrite was not
      observed in this process. Moreover, flow rate and nitrate concentration of the
      influent were observed to have a significant effect on nitrate removal
      efficiency. A sharp decline of nitrate removal efficiency was observed when the
      flow rate was greater than 50 L/d. The reactor had the ability to accommodate a
      wide range of pH levels (6.5 to 8.5) and dissolved oxygen (1.5 mg/L to 4 mg/L). A
      time-dependent decrease in nitrate removal efficiency was observed after 67 days
      of operation. The addition of fresh corncobs brought about a rapid increase of
      nitrate removal efficiency. Results showed that corncobs could be used as an
      economical and effective carbon source for denitrification.

PMID- 19378655
TI  - A preliminary investigation on the occurrence and distribution of antibiotics in
      the Yellow River and its tributaries, China.
AB  - This study investigated the residues of antibiotics present in the Yellow River
      and its tributaries. Ofloxacin, norfloxacin, roxithromycin, erythromycin, and
      sulfamethoxazole, were found in the river with mean concentrations from 25 to 152
      ng/L, and in certain tributaries from 44 to 240 ng/L. The other four analytes
      were all below the limits of quantification. The results indicated that the
      detected antibiotics in the middle and lower Yellow River were primarily from its
      tributaries and ambient wastewater discharge. The concentrations of the
      antibiotics detected in the river were greater than that in other rivers in
      Europe. The antibiotics in the river and its tributaries at ng/L concentrations
      found in this study are unlikely to induce lethal toxicity to aquatic organism
      but could cause chronic ecological effects.

PMID- 19378656
TI  - Changes in mixed liquor and organic foulant properties affect membrane fouling
      for non-nitrifying and nitrifying biological conditions.
AB  - A submerged membrane bioreactor treated settled municipal wastewater at a non
      nitrifying solids retention time (SRT) condition (2 days) and a nitrifying SRT
      condition (10 days), to determine the effect of nitrification on mixed liquor
      properties and membrane fouling. Membrane fouling rates were almost 10 times
      greater at the 2-day SRT compared with the 10-day SRT, and results showed
      increased concentrations of high-molecular-weight organic molecules at the 2-day
      SRT. The Fourier transform infrared spectroscopy (FTIR) results of the fouled
      membrane from the 2-day SRT exhibited strong peaks for carbohydrates, while the
      fouled membrane from the 10-day SRT did not. This is consistent with the fact
      that, although the total carbohydrate soluble microbial product concentration was
      highest at the 10-day SRT, the carbohydrate consisted of mostly low-molecular
      weight (< 1 kDa) molecules, and 97% of this carbohydrate passed through the
      membrane at the 10-day SRT.

PMID- 19378657
TI  - Effect of sulfide inhibition and organic shock loading on anaerobic biofilm
      reactors treating a low-temperature, high-sulfate wastewater.
AB  - To assess the long-term treatment of sulfate- and carbon-rich wastewater at low
      temperatures, anaerobic biofilm reactors were operated for over 900 days at 20
      degrees C and fed wastewater containing lactate and sulfate. Results showed the
      reactors could be operated at 20 degrees C with a load rate of 1.3 g-chemical
      oxygen demand (COD)/L x d or less and a sulfur loading rate (SLR) of 0.2 g-S/L x
      d, with no significant deterioration in performance. With acclimation periods,
      load rates of 3.4 g-COD/L x d and SLR of 0.3 g/L x d could be tolerated. Effluent
      dissolved sulfide and hydrogen sulfide levels were approximately 600 and 150 mg
      S/L, respectively, during this period. The effect of organic shock loading was
      also assessed. Reactors appeared to recover from one, but not two, lactate spikes
      of approximately 5000 mg-COD/L. Long-term stability was achieved in reactors
      containing large, stable populations of lactate- and propionate-degrading sulfate
      reducing bacteria and aceticlastic methanogens.

PMID- 19378658
TI  - Effect of oxygen partial pressure and chemical oxygen demand loading on the
      biofilm properties in membrane-aerated bioreactors.
AB  - Membrane-aerated biofilms with oxygen and nutrients diffusing from the opposite
      sides possess distinct properties, including the ability to couple aerobic and
      anaerobic processes. The objective of this study was to examine the effects of
      oxygen partial pressure and chemical oxygen demand (COD) loading on biofilm
      properties. Two laboratory-scale membrane-aerated bioreactors were operated for a
      total of 283 days, with one reactor operated at 42, 60, and 89 kPa (0.41, 0.59,
      and 0.88 atm) oxygen, and the other reactor at 25 kPa (0.25 atm) oxygen (air
      control). The biofilm detached at the oxygen partial pressures of 60 and 89 kPa
      (0.59 and 0.88 atm) at a COD loading of 11.3 kg COD/1000 m2/d, but was sustained
      at the oxygen partial pressures of 25 and 42 kPa (0.25 and 0.41 atm), with a
      porous structure at the membrane interface at the COD loading of 11.3 kg COD/1000
      m2/d. Biofilm formation was improved at a higher COD loading. It is proposed that
      the loss of extracellular polymeric substances at the biofilm bottom is the cause
      for the biofilm detachment subjected to a higher oxygen partial pressure.

PMID- 19378659
TI  - Biodegradation and detoxification of reactive textile dye by isolated Pseudomonas
      sp. SUK1.
AB  - An isolated bacterium from a textile disposal site, Pseudomonas sp. SUK1, has the
      ability to decolorize the reactive textile dyes and methyl orange. This bacterium
      showed the potential to decolorize the textile dye Reactive Blue 59 at a high
      concentration (5 g/L(-1)), which is frequently used in the textile industry of
      Solapur, India. Induction in the activities of lignin peroxidase, azoreductase,
      and dichlorophenol indophenol reductase was observed during the decolorization of
      Methyl Orange and Reactive Blue 59. Methyl Orange (as model azo dye) was used to
      understand the mechanism of biodegradation by Pseudomonas sp. SUK1. The final
      product was identified as 1,4-benzenediamine, N, N-dimethyl by gas chromatography
      mass spectroscopy. Microbial and phytotoxicity studies revealed the nontoxic
      nature of the products of Reactive Blue 59.

PMID- 19378660
TI  - Characteristics of highway stormwater runoff in Los Angeles: metals and
      polycyclic aromatic hydrocarbons.
AB  - Stormwater runoff from three highway sites in Los Angeles, California, was
      monitored, during the 2000 to 2003 wet seasons. Correlations among heavy metals,
      polycyclic aromatic hydrocarbons (PAHs), and storm characteristics were performed
      using datasets collected for 62 storm events. Statistical correlation analyses of
      the event mean concentrations (EMCs) and mass first-flush ratios (MFFs) with
      storm characteristics were conducted to determine if the first flush is related
      to site or storm characteristics. This study agreed with other highway runoff
      characterization studies, in that strong correlations were observed among the
      heavy metals and between heavy metals and total PAHs, and total suspended solids
      were well correlated with most heavy metals. Only antecedent dry days among storm
      characteristics were reasonably well-correlated with the EMCs of heavy metals and
      total PAHs, and dissolved and total metals exhibited similar MFFs, with
      approximately 30 to 35% of the mass being discharged in the first 20% of the
      runoff volume.

PMID- 19378661
TI  - Effect of sonication on electro-oxidation of organic pollutants in saline
      wastewater.
AB  - The aim of this work is to study the effect of ultrasound in pollution
      attenuation during electro-oxidation. Attenuation of chemical oxygen demand (COD)
      and total Kjeldahl nitrogen (TKN) with and without sonication during electro
      oxidation was studied. Further, the power of ultrasound during electro-sonication
      was varied, and its effect on attenuation of COD and TKN was studied. It was
      found that introduction of sonication could enhance pollution attenuation. It was
      also observed that pollution attenuation was proportional to the power of
      ultrasound. A significant level of pollution attenuation was attained during
      first 15 minutes of electro-sonication. Total current efficiency and anode
      efficiency were found to be proportional to the power of ultrasound, up to 100 W.
      Increasing the power more than 100 W did not render a significant increase in the
      total current efficiency and anode efficiency. Energy consumption for electro
      oxidation was found to be inversely proportional to the power of ultrasound, up
      to 100 W.

PMID- 19378662
TI  - Research note: modeling of the water quality of Buyuksu Stream, Bolu, Turkey.
AB  - The QUAL2E model was applied to the Buyuksu Stream, Bolu, Turkey, to predict the
      effect of conventional and industrial pollutant sources on stream quality. The
      model parameters were conditioned using data from eight sampling stations on a 24
      km stretch of the stream during a steady-state period between May 2003 and June
      2004. The higher biochemical oxygen demand (> 50 mg/L) and lower dissolved oxygen
      concentrations measured (< 4.0 mg/L), with their expected values, indicated that
      the water quality of the Buyuksu Stream was threatened by industrial and domestic
      pollution. The oxygen-sag curves obtained by the model calculations proved that
      discharges of the Bolu City wastewater and wood-processing plant effluent were
      the two primary pollutant sources affecting the stream. Results suggested that
      the conditioned model can be used as a tool to show the effects of pollutant
      sources on the Buyuksu Stream and to assess improvements expected by reducing the
      contribution of pollutant sources.

PMID- 19378663
TI  - "Social worth" will not affect allocation of scarce resources in a pandemic or
      disaster: political correctness, sophistry, or reality?

PMID- 19378664
TI  - Bioterrorism versus radiological terrorism: notes from a bio/nuclear
      epidemiologist.
AB  - The antiterrorism and disaster planning communities often speak of the high
      potential for bioterrorism and possible potential for radioterrorism,
      specifically the explosion of a fission device on US soil. Information gained
      from an epidemiologist's work in the national and international scene, which
      inevitably involves Intel regarding the cultures and subcultures being studied,
      suggest that bioterrorism is far less likely to be a major threat, that has been
      over-emphasized at the state level due to warnings from Homeland Security, and
      that Homeland Security itself appears biased toward bioterrorism of late with
      very little available rational basis.

PMID- 19378666
TI  - Emergency drills and exercises in healthcare organizations: assessment of
      pediatric population involvement using after-action reports.
AB  - BACKGROUND: Although the Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO) requires healthcare organizations to demonstrate disaster
      preparedness through the use of disaster exercises, the evaluation of pediatric
      preparations is often lacking. Our investigation identified, described, and
      assessed pediatric victim involvement in healthcare organizations' disaster
      drills and exercises using data from after-action reports. METHODS: Following the
      IRB approval, the authors reviewed the after-action reports generated by
      healthcare organizations after a disaster drill and exercise, as a self-assessed
      reporting tool for JCAHO regulations. Forty-nine of these reports that were
      voluntarily supplied to the emergency medical services agency were collected. The
      authors analyzed the data using quantitative and qualitative analytic approaches.
      RESULTS: Only nine reports suggested pediatric involvement. Hospitals with large
      bed capacity (M = 465.6) tended to include children in exercises compared with
      smaller facilities (M = 350.8). Qualitative content analysis revealed themes such
      as lack of parent-child identification and family reunification systems,
      ineffective communication strategies, lack of pediatric resources and specific
      training, and unfamiliarity with altering standards of pediatric care during a
      disaster. CONCLUSIONS: Although many organizations are performing disaster
      exercises, most are not including pediatric concerns. Further work is needed to
      understand the basis for this gap in emergency preparedness. Overall, pediatric
      emergency planning should be a high priority for this vulnerable population.

PMID- 19378665
TI  - Mortality and injury following the 2007 Ica earthquake in Peru.
AB  - OBJECTIVE: To quantify earthquake injury and mortality from the 2007 Ica
      earthquake in Peru and to assess earthquake-related risk and vulnerability.
      DESIGN: A population-based cluster survey of households in the region most
      affected by the earthquake. A stratified cluster survey design was used to allow
      for comparison between urban, periurban, and rural areas, where different
      outcomes were anticipated as a result of variation in building practices and
      access to post-earthquake assistance. A total of 42 clusters of 16 households
      were planned to allow for comparison between the location types and to ensure
      adequate spatial coverage. SETTING: The four affected provinces in Southern Peru:
      Ica, Pisco, Chincha, and Canete. PARTICIPANTS: A total of 672 randomly selected
      households with a combined population of 3,608 individuals, of which 3,484 (97
      percent) were reported as household members on the day of the earthquake.
      RESULTS: Mortality and injury rates in the four most affected provinces were
      estimated at 1.4 deaths/ 1,000 exposed (95 CI: 0.5-3.3) and 29 injuries/1,000
      exposed (95 CI: 6-52). Older adults and members of households of lower
      socioeconomic status faced increased risk of injury. No significant differences
      in injury rates were observed between rural, urban, and peri-urban residence
      areas. CONCLUSIONS: Populations of lower socioeconomic status faced increased
      risk of injury; however, no differences in injury rates were observed between
      rural, urban, and peri-urban communities. Study findings suggest that earthquake
      preparedness and mitigation efforts should focus on population subgroups of lower
      socioeconomic in both rural and urban areas of earthquake-prone regions.

PMID- 19378667
TI  - Humanitarian assistance and disaster relief: changing the face of defense.
AB  - The US Department of Defense (DOD) is evolving to meet new security challenges in
      the twenty-first century. Today's challenges result from growing political,
      environmental, and economic instability in important areas of the globe that
      threaten national and global security. Immediate outreach to foreign nations in
      times of violent instability or natural disaster fosters security and stability
      both for the affected country and for the United States. Foreign humanitarian
      assistance (FHA) is a rapidly evolving military mission that addresses conflict
      prevention, conflict, postconflict, and natural disasters. With DOD's extensive
      global medical resources, it is often uniquely qualified to execute a critical
      role in relief and/or public health efforts. When and how the American military
      will act in FHA and disaster relief is a still evolving doctrine with three
      issues deserving particular attention: aligning operations with host government
      leadership, preserving humanitarian space, and tailoring the US military's unique
      resources to the specific political and medical situation at hand. The DOD's
      response to a large-scale earthquake in Peru suggests useful approaches to these
      three issues, provides a template for future FHA mission, and points to strategic
      decisions and operational capabilities that need further development to establish
      the FHA mission firmly within DOD's repertoire of security engagement activities.

PMID- 19378668
TI  - Multiple information sources in the analysis of a disaster.
AB  - OBJECTIVE: Disasters are complex events making epidemiologic studies and
      determination of accurate denominators difficult due to the poor nature of
      available records. However, these data are essential to perform useful
      calculations and accurate descriptions of disaster medical impacts. This study
      was undertaken to identify the availability and utility of various information
      sources in the analysis of a mass casualty disaster. In addition, characteristics
      of cases presenting for care are described. DESIGN: This is a retrospective
      cohort study abstracting medical records and other documents relating to an
      explosion and fire. Public domain documents are obtained by written request or by
      filing a Freedom of Information Act (FOIA) request. SETTING: A rural EMS and
      tertiary hospital. CASES: Individuals directly exposed to the forces of the
      explosion. OUTCOME MEASURES: The number of cases detected by various information
      sources. In addition, the demographics, dispositions, and nature of the physical
      injuries of the cases are reported. RESULTS: Seven sources of case information
      were identified. The most cases were identified by investigative agencies (33)
      and the fewest by medical records (18). Rates include; injury 0.68, admission
      0.20, and operative 0.14, with no deaths. Case locations during the explosion
      were determined for all cases. No association was noted between admission and
      location in the building. CONCLUSIONS: This study demonstrates the availability
      and usefulness of data in the public domain. Using FOIA requests or partnerships
      with public or private agencies may more clearly define denominator data in
      epidemiologic evaluations of disasters.

PMID- 19378669
TI  - A decision framework for coordinating bioterrorism planning: lessons from the
      BioNet program.
AB  - BACKGROUND: Effective disaster preparedness requires coordination across multiple
      organizations. This article describes a detailed framework developed through the
      BioNet program to facilitate coordination of bioterrorism preparedness planning
      among military and civilian decision makers. METHODS: The authors and colleagues
      conducted a series of semistructured interviews with civilian and military
      decision makers from public health, emergency management, hazardous material
      response, law enforcement, and military health in the San Diego area. Decision
      makers used a software tool that simulated a hypothetical anthrax attack, which
      allowed them to assess the effects of a variety of response actions (eg, issuing
      warnings to the public, establishing prophylaxis distribution centers) on
      performance metrics. From these interviews, the authors characterized the
      information sources, technologies, plans, and communication channels that would
      be used for bioterrorism planning and responses. The authors used influence
      diagram notation to describe the key bioterrorism response decisions, the
      probabilistic factors affecting these decisions, and the response outcomes.
      RESULTS: The authors present an overview of the response framework and provide a
      detailed assessment of two key phases of the decision-making process: (1) pre
      event planning and investment and (2) incident characterization and initial
      responsive measures. The framework enables planners to articulate current
      conditions; identify gaps in existing policies, technologies, information
      resources, and relationships with other response organizations; and explore the
      implications of potential system enhancements. CONCLUSIONS: Use of this framework
      could help decision makers execute a locally coordinated response by identifying
      the critical cues of a potential bioterrorism event, the information needed to
      make effective response decisions, and the potential effects of various decision
      alternatives.

PMID- 19378670
TI  - The current state of affairs for disaster planning for a nuclear terrorist
      attack.
AB  - The author presents current thinking on the effects of an atomic bomb blast from
      a medical point of view and will argue that current US Federal plans for a
      nuclear disaster are simply crude, insufficient, disarticulated, and principally
      relies on martial law as a means of crowd control. The simple physics of a fusion
      reaction bomb is discussed along with the plans of other countries, apparently
      "secret"American plans, which show a poor knowledge of the physics of nuclear
      bombs as well as poor insight into what will be needed to help the maximum number
      of citizens. An alternative plan involving computer modeling and educating the
      public to the effects of a fission explosion are presented. The key issue of
      statewide planning is discussed, as the Federal government has dumped medical
      problems on "the local level."

PMID- 19378671
TI  - A rich and varied offering.

PMID- 19378672
TI  - The CTTO registry: is the CT really necessary?

PMID- 19378673
TI  - "Stent 4 Life" targeting PCI at all who will benefit the most. A joint project
      between EAPCI, Euro-PCR, EUCOMED and the ESC Working Group on Acute Cardiac Care.

PMID- 19378674
TI  - Keynote address--EuroPCR 2008, Barcelona, May 14th, 2008. Transcatheter aortic
      valve implantation: state of the art.

PMID- 19378675
TI  - First-in-man (FIM) study of the Stentys bifurcation stent--30 days results.
AB  - AIMS: We report the acute and 30 day results of the OPEN I study, a multicentre
      prospective single arm study evaluating the safety and feasibility of the Stentys
      bifurcation stent. METHODS AND RESULTS: The Stentys stent is a provisional, self
      expanding nitinol drug eluting or bare metal stent with small interconnections
      that can be disconnected by balloon angioplasty to provide access to the side
      branch and full ostium coverage. Forty patients with de novo coronary bifurcation
      lesions were enrolled to be clinically followed-up over four years. In addition
      to angiographic QCA evaluation, documentary IVUS and/or OCT were used in all
      cases to assess the stent's deployment. The patient population consisted of 85%
      males with an average age of 62 years. Almost half had previous PCI, 31% previous
      MI and 5% previous CABG. The majority of lesions (80%) involved the LAD-D, 42% of
      the patients had disease affecting the side-branch, with all three arms diseased
      in 24% of the cases. The average lesion length in the main branch was 12.95 +/-
      3.63 mm with a bifurcation angle of 55 degrees (range 30 degrees - 80 degrees).
      Procedural success was achieved in 39/40 cases (95.5%) due to inability to track
      the stent in one patient with an extremely tortuous vessel. In total 6 (15%)
      paclitaxel eluting and 33 (85%) BMS Stentys stents were successfully implanted,
      and simple disconnection of the stent mesh overlying the SB ostium was achieved
      in 37/39 cases (94.9%); in two cases, disconnection was not attempted. The MACE
      at 30 days was 5.1% as a result of one non Q-wave MI following the procedure and
      one ischemia-driven revascularisation six days after the procedure. CONCLUSIONS:
      This first-in-man (FIM) study demonstrates that the Stentys stent is safe and
      feasible resulting in an excellent procedural success rate and a low MACE rate.
      The struts can be easily and safely disconnected to perform provisional stenting.

PMID- 19378676
TI  - TAXUS VI final 5-year results: a multicentre, randomised trial comparing polymer
      based moderate-release paclitaxel-eluting stent with a bare metal stent for
      treatment of long, complex coronary artery lesions.
AB  - AIMS: To assess the long-term safety and efficacy of the paclitaxel-eluting TAXUS
      moderate-release (MR) investigation-only stent for the treatment of long, complex
      coronary artery lesions. METHODS AND RESULTS: TAXUS VI was a prospective, double
      blind, multicentre trial wherein 446 patients were randomised between a TAXUS
      Express MR stent and an uncoated Express Control stent. At 5-years, the overall
      rate of major adverse cardiac events (MACE) was similar in the two groups at
      27.8% in control and 31.3% in TAXUS (P = 0.61), including similar rates for stent
      thrombosis. The target vessel revascularisation (TVR) rate was 23.7% in control
      and 22.2% in TAXUS (P = 0.45) with a non-target lesion revascularisation (non
      TLR) rate of 5.1% in control and 10.9% in TAXUS (P = 0.0274) and a TLR rate of
      21.4% in control and 14.6% in TAXUS (relative reduction, 32%; P = 0.0325).
      Furthermore, subgroup analysis revealed that the TLR benefit of TAXUS was
      preserved among study groups including small vessels, long lesions and patients
      receiving multiple overlapping stents. CONCLUSIONS: Treatment of complex coronary
      lesions with the TAXUS MR stent demonstrated similar MACE, similar TVR, and
      reduced TLR rates compared with control through five years. Based on these
      positive results, the aetiology of increased non-TLR TVR rate in TAXUS remains
      unclear.

PMID- 19378677
TI  - Interventional treatment in diabetics in the era of drug-eluting stents and
      compliance to the ESC guidelines: lessons learned from the Euro Heart Survey
      Programme.
AB  - AIMS: The objective of the study is to determine the demographics and the in
      hospital outcome of diabetic and non-diabetic patients treated with percutaneous
      coronary interventions (PCI) in Europe, to report the type of equipment and
      technology used for PCI procedures in diabetics and to clarify whether the
      treatment of diabetic patients complies with current European Society of
      Cardiology (ESC) guidelines. METHODS AND RESULTS: A total of 14,458 patients
      treated with PCI were enrolled from 29 member countries of the ESC between June
      2005 and January 2006. Data were collected on patient characteristics and
      treatment, using new Cardiology Audit and Registration Data standards. In total,
      3603 patients (24.9%) were diabetic. Diabetics were older, more often female and
      had a higher body mass index than non-diabetics. Diabetics had higher rates of
      hypercholesterolaemia and hypertension, while current smokers were more frequent
      in the non-diabetics. Diabetics also had significantly higher rates of previous
      cardiovascular events. Clopidogrel was administered only in 48.1% of diabetic
      patients before PCI, while IIb/IIIa inhibitors were 22.9% during PCI. At
      discharge, there was a major adjustment of treatment with increases in the use of
      Beta-blocker (80.4%), angiotensin converting enzyme inhibitor (ACEI, 71.3%) and
      statins (89.8%) compared with on admission (Beta-blocker 60.9%, ACEI 55.0%,
      statin 63.1%). In-hospital mortality was higher in diabetics (1.8% vs 1.2%)
      although the in-hospital MACCE rate was not significantly different (3.6% vs.
      3.0%, p = 0.09). CONCLUSIONS: Diabetic patients treated with PCI were older with
      more comorbidity. According to ESC guideline, the under-usage of clopidogrel, GP
      IIb/IIIa inhibitors should be improved. PCI is now taken as a good opportunity to
      adjust the use of appropriate medication.

PMID- 19378678
TI  - Impact of atherosclerotic disease progression on mid-term clinical outcome in
      diabetic patients in the drug-eluting stent era.
AB  - AIMS: To determine whether repeat revascularisation (RR) in diabetic patients
      treated with prior drug-eluting stents (DES) is the result of either DES
      restenosis or native progression of atherosclerotic disease in the coronary
      vasculature, and to evaluate the impact of atherosclerotic disease progression on
      the midterm clinical outcome. METHODS AND RESULTS: We followed 316 consecutive
      diabetic patients (227 men, age 69 +/- 9 years) treated between June 2005 and
      September 2006 with at least one DES. During the follow-up (mean 590 +/- 194
      days) the cumulative incidence of major adverse clinical events (MACE; death, non
      fatal myocardial infarction [MI] and target vessel revascularisation [TVR]) was
      17.1%. Thirty-eight patients underwent RR (37 PCI, 1 coronary artery bypass graft
      [CABG]). In 22 patients RR was performed for restenosis (18 after DES
      implantation and 4 after BMS implantation); four of these patients also required
      treatment for atherosclerotic disease progression (ADP). In 16 patients, PCI was
      performed for symptomatic ADP without restenosis. Thus ADP contributed to 53% of
      RR procedures and to 42% of TVR. Furthermore, in 6 of 10 patients (60%) admitted
      for MI, the culprit lesion was the result of ADP. Only history of PCI and PCI of
      the left main before the index procedure were found to be independent predictors
      for development of significant de novo lesion at follow-up (OR 4.1, 95% CI 1.6
      10.4, p = 0.002 and OR 4.7, 95% CI 0.003, p = 0.003). No traditional risk factors
      were found to be predictors. CONCLUSIONS: Atherosclerotic disease progression was
      the cause of repeat revascularisation in more than 50% of diabetic patients
      treated previously with DES and had an important impact on their mid-term
      clinical outcome. MACE rates in clinical trials with long-term follow-up of
      diabetic patients can thus be influenced by native disease progression rather
      than DES failure and therefore should be interpreted with caution when addressing
      comparison of DES efficacy in diabetic patients.

PMID- 19378679
TI  - Incidence of stent thrombosis in patients with drug eluting stents and short-term
      dual antiplatelet therapy.
AB  - AIMS: This study sought to investigate the incidence of stent thrombosis (ST) in
      patients treated with drug-eluting stents (DES) and clearly defined short-term
      dual antiplatelet therapy (DAT) for three or six months for sirolimus-eluting
      stents (SES) or paclitaxel-eluting stents (PES), respectively. METHODS AND
      RESULTS: A series of 1023 consecutive patients with 1,414 stented lesions and
      prescribed short-term DAT were followed for at least two years after DES
      implantation. The individual durations of DAT, the rate of ischaemic events, and
      survival status were assessed. Follow-up was completed for 1017 patients (99.4%)
      with a mean follow-up of 3.0 +/- 0.7 years. DAT duration was 2.8 +/- 0.4 and 5.9
      +/- 0.8 months in patients with SES and PES, respectively. Adherence to continued
      single antiplatelet therapy was 98.4%. We identified 14 patients with definite ST
      (1.4%) and no patients with probable ST with a cumulative incidence of 0.6% at 30
      days, of 0.8% at one year, of 1.2% at 2 years, and of 1.4% at three years.
      CONCLUSIONS: Definite or probable ST after DES implantation and short DAT occurs
      with a cumulative incidence of 1.4% at 3 years if excellent patient adherence to
      the continued single antiplatelet therapy can be achieved.

PMID- 19378680
TI  - Percutaneous coronary intervention for chronic total occlusions: the role of side
      branch obstruction.
AB  - AIMS: The aim of this study was to review all percutaneous coronary interventions
      (PCI) performed in our department for chronic total occlusions (CTO) over the
      last three years, and analyse the success rate and complications. METHODS AND
      RESULTS: We retrospectively studied all PCls for total occlusions of more than
      four weeks duration, performed between 2004 and 2006, after excluding multivessel
      PCI, venous grafts and in-stent restenosis (n=106 cases). The in-hospital
      complications were recorded; periprocedural myocardial infarction (MI) was
      defined as elevation of troponin I more than 3 times the upper reference limit.
      Procedural success was defined as angiographic success and absence of major
      adverse cardiac events (MACE: death, large MI, emergency bypass). Logistic
      regression analysis was used to determine predictors of success and
      complications. The procedural success was 77%, and was mainly associated with
      duration of occlusion less than three months (OR 4.17, 95% CI 1.23-14.28, p =
      0.02), preprocedural TIMI 1 coronary flow (OR 3.29, 95% CI 1.00-10.82, p = 0.05)
      and absence of ipsilateral collaterals (OR 4.54, 95% CI 1.35-16.67, p = 0.01).
      Periprocedural MI occurred in 12 cases (12%), while MACE occurred in 3 (3%). The
      only parameter significantly associated with periprocedural MI was the
      obstruction of side-branches (with diameter >1 mm) within 5 mm of the CTO (OR
      10.00, 95% CI 1.76-56.67, p < 0.01). CONCLUSIONS: In our CTO cohort the success
      rate was 77%, with a low complication rate. Periprocedural MI was mainly due to
      obstruction of side-branches.

PMID- 19378681
TI  - Computed tomography in total coronary occlusions (CTTO registry): radiation
      exposure and predictors of successful percutaneous intervention.
AB  - AIMS: There is no mention in the current "appropriateness criteria for CTCA" of
      the need of CTCA investigation prior to an attempt at recanalisation of a CTO. To
      define better the role of CTCA in the treatment of patients with CTOs, we
      performed CTCA in a consecutive cohort of eligible patients who were scheduled
      for percutaneous recanalisation of a CTO. METHODS AND RESULTS: Symptomatic
      patients due to a CTO suitable for percutaneous treatment were included. One
      hundred and thirty-nine (142 CTOs) patients were studied. Overall success rate
      was 62.7%. By CTCA, the occlusion length was 24.9 +/- 18.3 vs. 30.7 +/- 20.7 mm
      in successful and failed cases (p = 0.1), but the frequency of patients with an
      occlusion length >15 mm was different, i.e., 63.2% vs. 82.7%, respectively (p =
      0.02). Severe calcification, (> 50% CSA) was more prevalent in failed cases
      (54.7% vs. 35.9%, p = 0.03). Calcification at the entry of the occlusion was
      present in 58.5% of the failures vs. 41.6% of the successful cases (p = 0.04),
      while calcium at the exit was not different. The length of calcification was 8.5
      +/- 8.4 vs. 5.5 +/- 6.6 mm in the failed and successful cases respectively (p =
      0.027). By multivariable analysis, the only independent predictor of procedural
      success was the absence of severe calcification as defined by CTCA. The mean
      effective radiation dose of the PCI was 39.3 +/- 30.1 mSv. The mean effective
      radiation dose of CT scan was 22.4 mSv: 19.2 +/- 6.5 mSv for contrast-enhanced
      scan, 3.2 +/- 1.7 mSv for calcium scoring scan. CONCLUSIONS: More severe
      calcified patterns, as assessed by CTCA, are seen in failed cases. The radiation
      exposure during a CT scan prior to a CTO PCI is considerable, and further studies
      are required to determine whether this extra diagnostic study is warranted.

PMID- 19378682
TI  - Primary percutaneous coronary intervention for acute myocardial infarction
      secondary to acute left main coronary occlusion in an institution without on-site
      cardiothoracic surgical support.
AB  - AIMS: There is no consensus on the optimal management of acute myocardial
      infarction due to acute left main coronary occlusion (LMCO). We evaluated the
      feasibility of primary percutaneous coronary intervention (PCI) for acute LMCO in
      an institution without on-site cardiothoracic surgical (CTS) support. METHODS AND
      RESULTS: We retrospectively identified 20 patients, median age 67 years (range 38
      to 81). Sixteen patients presented with cardiogenic shock. All patients required
      intra-aortic balloon pump counterpulsation and inotropic support. Sixteen
      patients underwent stenting and four had balloon angioplasty only. Thrombolysis
      In Myocardial Infarction 3 flow was restored in 13 patients. Post-PCI, six
      patients were transferred to a tertiary institution for further care: three
      underwent extracorporeal membrane oxygenation (ECMO), one underwent both ECMO and
      coronary artery bypass grafting (CABG), one died before ECMO initiation and one
      stabilised without further intervention. Thirteen patients died in-hospital.
      There was one subsequent death out of the seven hospital survivors, with median
      follow-up 390 days (range 60 to 660 days). There was a trend towards survival
      with a shorter door-to-balloon time (p = 0.07). CONCLUSIONS: Primary PCI may be a
      feasible initial revascularisation strategy for acute LMCO in centres without on
      site CTS support.

PMID- 19378683
TI  - Cheatham platinum (CP) and Palmaz stents for cardiac and vascular lesions
      treatment in patients with congenital heart disease.
AB  - AIMS: To compare Cheatham Platinum (CP) stent and Palmaz stent for the treatment
      of native and postoperative lesions of congenital heart disease (CHD) patients.
      METHODS AND RESULTS: From January 1998 to December 2007, 96 CP stents and 77
      Palmaz stents were implanted in 89 and 64 CHD patients. All stents could be
      deployed. Decrease in pressure gradient was higher with the CP than with the
      Palmaz stent (36.1 +/- 23 and 23.4 +/- 18.3 mmHg, p = 0.004). The procedure was
      more often successful with a CP than with a Palmaz stent (96% and 88% of
      patients, p = 0.03). Stent-related complications were more rarely observed with
      the CP than with the Palmaz stent (9% and 27%, p = 0.007). The incidence of
      vascular dissection was lower with CP than with Palmaz stent (1% and 6%), the
      incidence of stent migration was similar in the two groups (8% and 6%). Balloon
      burst, never observed in the CP stent group, was frequent in the Palmaz group (0%
      and 11%, p = 0.001). There were no procedural deaths. The need for urgent surgery
      was similar in the two groups (2% and 1%). CONCLUSIONS: Our findings show a
      superiority of the CP over the Palmaz stent concerning efficacy and reduction of
      complications rate for the treatment of cardiac and vascular lesions of children
      and young adults with CHD.

PMID- 19378684
TI  - In vivo characterisation of coronary plaques with conventional grey-scale
      intravascular ultrasound: correlation with optical coherence tomography.
AB  - AIMS: Although intravascular ultrasound (IVUS) is widely used, there is limited
      published data on its accuracy in defining plaque characteristics in vivo.
      Optical coherence tomography (OCT) is a high-resolution imaging technique that
      takes advantage of the pronounced optical contrast between the components of
      normal and diseased vessels. The aim of this study was to evaluate the ability of
      conventional grey-scale IVUS in identifying in vivo coronary plaque
      characteristics, in particular lipid content as a marker of the vulnerable
      plaque, when compared to OCT. METHODS AND RESULTS: In patients undergoing cardiac
      catheterisation, IVUS and OCT imaging was performed. Detailed qualitative
      analysis of lipid-rich plaque, calcific plaque, and plaque disruption were
      performed at corresponding sites using both modalities. A total of 146 matched
      sites were available for analysis. When compared to OCT, sensitivity of IVUS for
      identification of lipid pools was low (24.1%) but specificity was high (93.9%).
      The sensitivity and specificity of IVUS for detection of calcific plaque and
      plaque disruption were respectively 92.9%; 66.4%, and 66.7%; 96.1%. CONCLUSIONS:
      Conventional grey-scale IVUS may not be a reliable imaging modality for detection
      of lipid-rich and hence vulnerable plaques. This has important implications in
      using conventional grey-scale IVUS to identify the vulnerable plaque.

PMID- 19378685
TI  - Re-examining minimal luminal diameter relocation and quantitative coronary
      angiography--intravascular ultrasound correlations in stented saphenous vein
      grafts: methodological insights from the randomised RRISC trial.
AB  - AIMS: Angiographic parameters (such as late luminal loss) are common endpoints in
      drug-eluting stent trials, but their correlation with the neointimal process and
      their reliability in predicting restenosis are debated. METHODS AND RESULTS:
      Using quantitative coronary angiography (QCA) data (49 bare metal stent and 44
      sirolimus-eluting stent lesions) and intravascular ultrasound (IVUS) data (39
      bare metal stent and 34 sirolimus-eluting stent lesions) from the randomised
      Reduction of Restenosis In Saphenous vein grafts with Cypher stent (RRISC) trial,
      we analysed the "relocation phenomenon" of QCA-based in-stent minimal luminal
      diameter (MLD) between post-procedure and follow-up and we correlated QCA-based
      and IVUS-based restenotic parameters in stented saphenous vein grafts. We
      expected the presence of MLD relocation for low late loss values, as MLD can
      "migrate" along the stent if minimal re-narrowing occurs, while we anticipated
      follow-up MLD to be located close to post-procedural MLD position for higher late
      loss. QCA-based MLD relocation occurred frequently: the site of MLD shifted from
      post-procedure to follow-up an "absolute" distance of 5.8 mm [2.5-10.2] and a
      "relative" value of 29% [10-46]. MLD relocation failed to correlate with in-stent
      late loss (rho = 0.14 for "absolute" MLD relocation [p = 0.17], and rho=0.03 for
      "relative" relocation [p = 0.811). Follow-up QCA-based and IVUS-based MLD values
      well correlated in the overall population (rho = 0.76, p < 0.001), but QCA
      underestimated MLD on average 0.55 +/- 0.49 mm, and this was mainly evident for
      lower MLD values. Conversely, the location of QCA-based MLD failed to correlate
      with the location of IVUS-based MLD (rho = 0.01 for "absolute" values--in mm [p =
      0.911, rho = 0.19 for "relative" values--in % [p = 0.111). Overall, the ability
      of late loss to "predict" IVUS parameters of restenosis (maximum neointimal
      hyperplasia diameter, neointimal hyperplasia index and maximum neointimal
      hyperplasia area) was moderate (rho between 0.46 and 0.54 for the 3 IVUS
      parameters). CONCLUSIONS: These findings suggest the need for a critical re
      evaluation of angiographic parameters (such as late loss) as endpoints for drug
      eluting stent trials and the use of more precise techniques to describe
      accurately and properly the restenotic process.

PMID- 19378686
TI  - Prevalence and characteristics of major and minor coronary artery anomalies in an
      adult population assessed by computed tomography coronary angiography.
AB  - AIMS: There is conflicting data regarding the prevalence and characteristics of
      coronary artery anomalies (CAAs). We sought to explore the prevalence and
      characteristics of major and minor CAAs using computed tomography coronary
      angiography (CCTA). METHODS AND RESULTS: We prospectively studied 577 patients in
      sinus rhythm referred for control of stents or for screening due to the presence
      of multiple risk factors (53%), or due to chest pain, equivalent symptoms or
      inconclusive stress tests (47%). 40 and 64 slice CT scanners were used. The mean
      age was 61 +/- 11 years and 81% were male. We identified CAAs in 121 (21.0%)
      patients. Anomalous origination of a coronary artery from the opposite sinus
      (ACAOS) were identified in 6/577 (1%) patients. Coronary ectasia or aneurysm was
      present in 10/577 (1.7%) patients. One-hundred and nine intramuscular segments
      (MB) were found in 100/577 (17.3%) patients. Coronary hypoplasia was identified
      in 3/577 (0.5%) patients, all involving the RCA, and 3/577 (0.5%) patients had an
      absent left main coronary artery. None of the segments with ACAOS (proximal
      segment) or MB had atherosclerotic plaque. CONCLUSIONS: CAAs were highly
      prevalent along the coronary tree and anatomical characteristics that might help
      stratify the risk and guide therapy of CAAs could be easily identified with CCTA.

PMID- 19378687
TI  - Novel method for real-time hybrid cardiac CT and coronary angiography image
      registration: visualising beyond luminology, proof-of-concept.
AB  - AIMS: During coronary angiography and percutaneous coronary interventions (PCI)
      only the lumen of the coronary vessel is imaged. The complete pathology of the
      vessel wall--namely the extent of calcification, structure of non-calcified
      plaque and lesion length--cannot be accurately determined. These can be imaged
      using coronary CT angiography (CTCA). We aimed to investigate the accuracy,
      feasibility, safety and value of a novel hybrid method encapsulating real-time
      registration of CTCA to coronary angiography images. The method is designed to
      seamlessly integrate into the routine catheterisation procedures and provide
      information to assist in decision making during the interventional procedure.
      METHODS AND RESULTS: Phantoms simulating the coronary tree were used to test the
      accuracy and potential of co-registration of information. Precision of the
      imaging system was tested using radio-opaque markers and distance between
      bifurcations. We included patients who underwent CTCA and also underwent cardiac
      catheterisation. Analysis and feasibility was performed offline in the first
      twenty patients and online in the following 19 patients. The online CTCA and
      angiography co-registration was performed by the AngioCt software program. The
      registration result was displayed on a separate screen in the catheterisation
      laboratory as a three-dimensional coronary tree and a curved multi-planar
      reformat (MPR) view. Preclinical validation showed that the co-registration of
      the coronary tree is feasible, and measurements of length and diameter are
      precise for all standard working angulations during coronary angiography. Real
      time registration was successful in all cases and aided in selection of the view
      that will provide the least foreshortening and no vessel overlapping, the length
      of balloons and stent to use and assisted in crossing chronic total occlusions
      (CTO). CONCLUSIONS: This is the first report of a novel method for online real
      time hybrid CTCA and angiography registration. In this pilot study we found that
      this method is feasible, accurate, and easy to use. It can be used for selecting
      the best working angulations for minimising foreshortening and vessel
      overlapping, determining stent size and location, and providing a reference
      vessel path and structure in cases of CTO.

PMID- 19378688
TI  - Plaque and shear stress distribution in human coronary bifurcations: a multislice
      computed tomography study.
AB  - AIMS: Early atherosclerosis is located in low wall shear-stress (WSS) regions,
      however plaques are also found in the high WSS sensing flow divider walls of
      coronary bifurcations. We assessed the plaque distribution and morphology near
      bifurcations non-invasively with 64-slice computed tomography in relation to the
      WSS distribution. METHODS AND RESULTS: We inspected 65 cross-sections near
      coronary bifurcations for the presence of plaque. Cross-sections were divided
      into four equal parts, which we numbered according to expected levels of WSS,
      with part I the lowest WSS (outer wall) and increasing WSS's in part II (inner
      bend), III (outer bend) and IV (flow divider). Of the cross-sections 88% had
      plaque. Of all parts I, 72% contained plaque. This was 62%, 38% and 31% in parts
      II, III and IV. In cross-sections with only 1 or 2 parts inflicted, plaque was
      found in part I and/or II in 94%. In 93% of the cross-sections with the flow
      divider inflicted, parts I and/or II were also inflicted. Plaque was never found
      exclusively in the flow divider part IV. CONCLUSIONS: We demonstrated that plaque
      is mostly present in low WSS regions, whereas plaque in high WSS regions is
      accompanied by plaque in adjacent low WSS regions. It is therefore plausible that
      plaque grows from the outer wall (low WSS) of the bifurcation towards the flow
      divider (high WSS).

PMID- 19378689
TI  - Incidence, patient characteristics and predictors of aborted myocardial
      infarction in patients undergoing primary PCI: prospective study comparing pre-
      and in-hospital abciximab pretreatment.
AB  - AIMS: This study was performed to assess the incidence, patient characteristics
      and predictors of aborted myocardial infarction (MI) in patients with ST-segment
      elevation MI (STEMI) undergoing primary percutaneous coronary intervention
      (PPCI). METHODS AND RESULTS: We enrolled 179 consecutive patients with STEMI
      within a fixed protocol for PPCI (Leiden MISSION! project); 90 patients received
      abciximab bolus in the hospital (in-hospital group) and 89 patients received
      abciximab bolus in the ambulance (pre-hospital group). Thirty-two patients (18%)
      fulfilled the criteria for an aborted MI. The incidence of aborted MI was four
      times higher in the pre-hospital abciximab group compared to the in-hospital
      group (OR = 4.2, 95% CI = 1.7-10.3). The median time between symptoms onset and
      abciximab bolus administration was significantly shorter in the aborted MI
      compared to established MI patients (70 vs. 115 min, p = 0.005). Multivariable
      analysis identified prehospital abciximab administration as the main predictor of
      aborted MI (OR = 2.86, 95% CI = 1.1-7.5). CONCLUSIONS: In patients with STEMI
      treated with PPCI, the incidence of aborted MI was 18%. Pre-hospital abciximab
      administration was the main predictor of aborted MI, and this effect was related
      to the initiation of treatment within the first two hours after symptoms onset
      and to the higher infarct related artery patency at presentation.

PMID- 19378690
TI  - The use of self-expanding stents in coronary bifurcations and beyond: a paradigm
      revisited.
AB  - Conventional tubular balloon expandable (BE) stent designs are poorly suited to
      coronary bifurcations, yielding highly variable results. For this reason, intense
      interest remains and industry development continues for dedicated bifurcation
      coronary stents to make treatment of such lesions more straightforward.
      Innovative designs have emerged, some balloon expandable, but also self
      expandable, based on the premise that nitinol based designs may conform more
      favourably than other metals to non-tubular vascular structures such as
      bifurcations. Through discussion of one of the early implantations of the first
      of these new age self-expanding designs, the Devax coronary bifurcation system,
      we outline the state-of-the-art use of self-expanding designs in percutaneous
      intervention to coronary bifurcations, and revisit an old paradigm with
      contemporary applications. The Devax system was the first of a new generation of
      self-expanding coronary stents after a more than 15 year lull in their
      development and was also the first dedicated drug eluting stent (DES) for
      bifurcations. It was first used in man in 2003. Other self-expanding designs have
      followed and shown promise in this setting, including Stentys and the Capella
      Sideguard. New indications have also emerged, including small vessels, addressed
      by the Cardiomind Sparrow and soft, unstable lesions, treated by the vProtect
      luminal shield. Of note, all the novel devices presented have a relative paucity
      of clinical data with no randomised clinical trials to date, but--if the
      contemporary results continue to be favourable--their indications may become more
      widespread in the future of coronary intervention.

PMID- 19378691
TI  - Information systems for mental health.

PMID- 19378692
TI  - Innovations in the utilization of health information technology in psychiatric
      services.
AB  - There is ever-increasing activity in applying information technology to various
      areas of healthcare, including mental health. Examples of innovations include
      applications in screening, treatment, clinical decision support, communication
      and coordination, telemedicine, Internet-based education and services, public
      health research, training and education, and bioinformatics. Issues and
      challenges include protection of privacy, managing narrative free text, assessing
      the reliability of information found online, and mitigating impact on clinical
      workflow. While many of the innovations described will not be fully realized
      until national information systems reach a larger scale, many are having a
      positive impact on mental healthcare today.

PMID- 19378693
TI  - The implementation of mental health information systems in developing countries:
      challenges and opportunities.
AB  - The aims are to examine the challenges and opportunities in the implementation of
      mental health information systems (MHIS) in developing countries as suggested by
      the World Health Organization (WHO) and explored by Gulbinat et al. (2008).
      Special recommendations for developing countries are: 1) MHIS should be linked to
      the general medical information system; 2) there is need for adoption, adaptation
      and validation of preferably self-administered instruments that are appropriate
      for different levels within the health care system; 3) developing countries must
      adopt innovative and "unconventional" approaches through utilization of community
      members, traditional doctors/healers and mid-cadre health workers, in addition to
      general doctors, for the delivery of mental health services.

PMID- 19378694
TI  - Outcome reporting bias in clinical trials.

PMID- 19378695
TI  - Interhemispheric communication in schizophrenia.

PMID- 19378697
TI  - [Towards a history of the family care of psychiatric patients].
AB  - INTRODUCTION: Inserting adults with psychic problems into families has recently
      been practiced in various European countries and also in Italy, where some mental
      health departments support such families. Beyond the well known story of Gheel,
      the etero and omofamily care of psychiatric patients has a forgotten history.
      METHODS: On the basis of unexplored and exceptionally rich sources from the
      archives of the asylums in Florence, as well as of the Province di Florence,
      which funded assistance to the mentally ill--this research focuses on the
      subsidized "domestic custody" of hundreds of psychiatric patients, who had
      already been institutionalized. Beginning in 1866, outboarding was supported by
      the provincial administration in Florence with the collaboration of the asylum
      medical direction. RESULTS: In the late 19th C. and in the early 20th C.
      prestigious psychiatrists sought alternatives to the institutionalisation. These
      alternatives involved varied participants in a community (the patients and their
      families, the administrators and the medical specialists, the neighborhood and
      the police). The families played a special role that historians of the psychiatry
      exclusively dedicated to the insane asylums have not really seen. CONCLUSIONS:
      The role of the families in the interaction with the psychiatric staff is not,
      even on a historiographical level, simply an additional and marginal chapter of
      the practices and of the culture of the mental health. These archival evidence
      contradicts some common places on the past of the Italian psychiatry before 1978,
      and provokes new reflections of possible relevance to the present.

PMID- 19378696
TI  - The global burden of mental disorders: an update from the WHO World Mental Health
      (WMH) surveys.
AB  - AIMS: The paper reviews recent findings from the WHO World Mental Health (WMH)
      surveys on the global burden of mental disorders. METHODS: The WMH surveys are
      representative community surveys in 28 countries throughout the world aimed at
      providing information to mental health policy makers about the prevalence,
      distribution, burden, and unmet need for treatment of common mental disorders.
      RESULTS: The first 17 WMH surveys show that mental disorders are commonly
      occurring in all participating countries. The inter-quartile range (IQR: 25th
      75th percentiles) of lifetime DSM-IV disorder prevalence estimates (combining
      anxiety, mood, externalizing, and substance use disorders) is 18.1-36.1%. The IQR
      of 12-month prevalence estimates is 9.8-19.1%. Prevalence estimates of 12-month
      Serious Mental Illness (SMI) are 4-6.8% in half the countries, 2.3-3.6% in one
      fourth, and 0.8-1.9% in one-fourth. Many mental disorders begin in childhood
      adolescence and have significant adverse effects on subsequent role transitions
      in the WMH data. Adult mental disorders are found to be associated with such high
      role impairment in the WMH data that available clinical interventions could have
      positive cost-effectiveness ratios. CONCLUSIONS: Mental disorders are commonly
      occurring and often seriously impairing in many countries throughout the world.
      Expansion of treatment could be cost-effective from both employer and societal
      perspectives.

PMID- 19378698
TI  - Employment status, aspirations and perceptions of support amongst psychiatric
      service users in Pavia, Italy.
AB  - AIMS: To describe the employment status of people using mental health service in
      Pavia, Italy; to explore their employment aspirations and perceptions of support
      to achieve these; and to test the feasibility of working with service users as
      researchers. METHOD: Face to face interviews carried out by two service user
      researchers with a consecutive sample of 200 service users attending the local
      psychiatric outpatient department using a translated version of a questionnaire
      developed for previous UK surveys. RESULTS: A higher proportion of survey
      participants (42.5%) were in paid work compared to the UK, but 62.4% of those in
      work were dissatisfied with their employment. Amongst unemployed participants,
      65.2% were interested in gaining employment but only 29.3% were receiving support
      to do so. Support was mainly limited to referral on to a generic disability
      organisation. The service user researchers carried out the survey to a high
      standard and reported benefits from undertaking the work. CONCLUSIONS: The
      results indicate a need in Pavia for specialist employment support using the
      Individual Placement and Support approach. Further development of service user
      involvement in research is indicated.

PMID- 19378699
TI  - What people with schizophrenia think about the causes of their disorder.
AB  - AIMS: To describe what users with schizophrenia think about the causes of their
      disorder. METHODS: In each of the 10 participating Italian mental health centres,
      25 users with schizophrenia were consecutively recruited and asked to complete
      the Users' Opinions Questionnaire (UOQ). RESULTS: 150 out of 198 respondents
      mentioned at least one social cause for their mental disorder, and 114 reported
      exclusively social causes. Family conflicts were the most frequently reported
      social cause (21%), followed by traumas (20%), work and study difficulties (17%),
      and psychological disturbances (17%). Ten percent of the respondents mentioned
      biological causes. Biological causes were more frequently reported by users who
      were aware of their diagnosis of schizophrenia, whereas social causes by those
      who just knew they suffered from a psychosis. Difficulties in social
      relationships were more frequently pointed out by respondents with an earlier
      onset of the illness and a higher number of compulsory admissions in the previous
      12 months. These users expressed more scepticism about the usefulness of the
      treatments they received, and perceived a greater social distance. CONCLUSIONS:
      Users' beliefs about the causes of their disorder should be taken into account by
      psychiatrists in order to improve their working alliance with them.

PMID- 19378700
TI  - Economic evaluation of a crisis resolution service: a randomised controlled
      trial.
AB  - AIMS: The use of specialised services to avoid admission to hospital for people
      experiencing mental health crises is seen as an integral part of psychiatric
      services in some countries. The aim of this paper is to assess the impact on
      costs and cost-effectiveness of a crisis resolution team (CRT). METHODS: Patients
      who were experiencing mental health crises sufficient for admission to be
      considered were randomised to either care provided by a CRT or standard services.
      The primary outcome measure was inpatient days over a six-month follow-up period.
      Service use was measured, costs calculated and cost-effectiveness assessed.
      RESULTS: Patients receiving care from the CRT had non-inpatient costs pounds
      sterling 768 higher than patients receiving standard care (90% CI, pounds
      sterling 153 to pounds sterling 1375). With the inclusion of inpatient costs the
      costs for the CRT group were pounds sterling 2438 lower for the CRT group (90%
      CI, pounds sterling 937 to pounds sterling 3922). If one less day spent as an
      inpatient was valued at pounds sterling 100, there would be a 99.5% likelihood of
      the CRT being cost-effective. CONCLUSION: This CRT was shown to be cost-effective
      for modest values placed on reductions in inpatient stays.

PMID- 19378701
TI  - [Child premorbid impairments in adult psychiatric patients attending Centres for
      Mental Health of Udine and Alto Friuli, Italy].

PMID- 19378702
TI  - Panic agoraphobic spectrum in psychiatrically healthy subjects: impact on quality
      of life.

PMID- 19378703
TI  - Teamwork, cooperation, innovation: clues in the Canadian success of stroke care.

PMID- 19378704
TI  - Managing unruptured intracranial aneurysms.

PMID- 19378705
TI  - Managing unruptured aneurysms: the ethical solution to the dilemma.

PMID- 19378706
TI  - Central nervous system imaging in mitochondrial disorders.
AB  - Imaging of central-nervous-system (CNS) abnormalities is important in patients
      with mitochondrial disorders (MCDs) since the CNS is the organ second most
      frequently affected in MCDs and some of them are potentially treatable.
      Clinically relevant imaging techniques for visualization of CNS abnormalities in
      MCDs are computed tomography, magnetic resonance imaging, and MR-spectroscopy.
      The CNS abnormalities in MCDs visualized by imaging techniques include stroke
      like lesions with cytotoxic or vasogenic edema, laminar cortical necrosis, basal
      ganglia necrosis, focal or diffuse white matter lesions, focal or diffuse
      atrophy, intra-cerebral calcifications, cysts, lacunas, hypometabolisation,
      lactacidosis, hemorrhages, cerebral hypo- or hyperperfusion, intra-cerebral
      artery stenoses, or moyamoya syndrome. The CNS lesions may proceed with or
      without clinical manifestations, why neuroimaging should be routinely carried out
      in all MCDs to assess the degree of CNS involvement. Some of these lesions may
      remain unchanged for years, some may show contiguous spread and progression, but
      some may even disappear, spontaneously or in response to medication. Dynamics of
      Stroke-like lesions may be positively influenced by L-arginine, dichloracetate,
      steroids, edavarone, or antiepileptics. Symptomatic treatment of CNS
      abnormalities in MCD patients may positively influence their outcome.

PMID- 19378707
TI  - Movements in brain death: a systematic review.
AB  - Brain death is the irreversible lost of function of the brain including the
      brainstem. The presence of spontaneous or reflex movements constitutes a
      challenge for the neurological determination of death. We reviewed historical
      aspects and practical implications of the presence of spontaneous or reflex
      movements in individuals with brain death and postulated pathophysiological
      mechanisms. We identified and reviewed 131 articles on movements in individuals
      with confirmed diagnosis of brain death using Medline from January 1960 until
      December 2007, using 'brain death' or 'cerebral death' and 'movements' or 'spinal
      reflex' as search terms. There was no previous systematic review of the
      literature on this topic. Plantar withdrawal responses, muscle stretch reflexes,
      abdominal contractions, Lazarus's sign, respiratory-like movements, among others
      were described. For the most part, these movements have been considered to be
      spinal reflexes. These movements are present in as many as 40-50% of heart
      beating cadavers. Although limited information is available on the determinants
      and pathophysiological mechanisms of spinal reflexes, clinicians and health care
      providers should be aware of them and that they do not preclude the diagnosis of
      brain death or organ transplantation.

PMID- 19378708
TI  - Intravenous thrombolysis for acute ischaemic stroke in young adult patients.
AB  - BACKGROUND: Intravenous tissue plasminogen activator (IV tPA) has been studied
      primarily in patients over age 50. We sought to describe baseline differences in
      adult patients < or = 50 years-old taken from a large prospective cohort of acute
      stroke patients treated with intravenous tPA (IV tPA) and to determine whether
      outcomes differed for this population. METHODS: Data (n = 1120) prospectively
      collected from the Canadian Alteplase for Stroke Effectiveness Study (CASES) were
      reviewed and patients aged < or = 50 years-old (n = 99) were compared with those
      aged > 50 years (n = 1021) with regards to baseline characteristics, symptomatic
      intracerebral haemorrhage (sICH), functional outcome at 90 days and death.
      RESULTS: Nine percent of patients were < or = 50 years-old. Among patients aged <
      or = 50 years, 40.4% were women and median age was 42 +/- 6.1 years (range 20 to
      50). They had significantly more current cigarette use but fewer other vascular
      risk factors than older patients (p < 0.05) and their baseline median NIHSS score
      was lower (13 versus 15, P = 0.001). Although this group was more likely to have
      a favourable 90-day outcome, multivariable regression confirmed that age < or =
      50 years, while independently associated with a decreased risk of death (RR 0.36,
      95% CI 0.14 to 0.95), was not itself predictive of favourable 90-day outcome or
      decreased risk of sICH. CONCLUSIONS: Adult patients < or = 50 years-old had fewer
      medical co-morbidities and a modestly lower baseline median NIHSS score than
      their older counterparts. Age < or = 50 years was independently associated with a
      decreased risk of death but not with favourable outcome or risk of sICH.

PMID- 19378710
TI  - Comparison of CTA to DSA in determining the etiology of spontaneous ICH.
AB  - BACKGROUND AND PURPOSE: To compare the efficacy of computed tomographic
      angiography (CTA) to that of digital subtraction angiography (DSA) in the
      detection of secondary causes of intracerebral hemorrhage (ICH). METHODS: Between
      January 2001 and February 2007 there were 286 patients that had both CTA and DSA
      for intracranial hemorrhage of all types. Those with primarily subarachnoid
      hemorrhage or recent trauma were excluded. Fifty-five patients formed the study
      cohort. Three reviewers independently analyzed the CTAs in a blinded protocol and
      classified them based on presence or absence of a secondary etiology. Results
      were compared with the reference standard DSA and kappa values determined for
      interobserver variability. RESULTS: The overall sensitivity, specificity,
      positive predictive value, negative predictive value and accuracy of CTA were
      89%, 92%, 91%, 91% and 91%, respectively. Kappa value for interobserver agreement
      ranged from 0.78 to 0.89. Two of four dural arteriovenous fistulas (dAVF) were
      missed on CTA by all three reviewers. CONCLUSION: CTA is nearly as effective as
      DSA at determining the cause of secondary intracerebral hemorrhage, but with a
      lower sensitivity for dAVFs. This supports the use of CTA as the first screening
      test in patients presenting with spontaneous ICH.

PMID- 19378709
TI  - Arterial Onyx embolisation of intracranial DAVFs with cortical venous drainage.
AB  - PURPOSE: To present our experience with the endovascular management of
      intracranial dural arteriovenous fistulas with direct cortical venous drainage by
      trans-arterial embolisation using Onyx. MATERIALS & METHODS: Between January 2004
      and April 2008, 12 consecutive high grade intracranial dural arteriovenous
      fistulas (Cognard type III (eight patients) or IV (three patients)) were treated
      by trans-arterial embolisation with Onyx. The majority of cases were treated by
      Onyx embolisation alone. One case had additional embolisation with n-butyl-2
      cyanoacrylate at the same session. Imaging follow-up was obtained in all but one
      patient (mean 3.6 months). RESULTS: Nine patients had a technical success at the
      end of the embolisation procedure with complete angiographic exclusion of the
      fistula. Two patients had a small residual fistula at the end of embolisation,
      one of which had residual mild cortical venous drainage. Both were stable at
      follow-up angiography. One patient had a residual fistula supplied by the
      ophthalmic artery, which was thought to be unsafe to embolise and was sent for
      surgery, which was curative. In one patient the microcatheter ruptured, with a
      fragment of the distal microcatheter left in the occipital artery. No clinical
      complications were observed in this series at clinical follow-up (mean 3.3
      months). Two patients were noted to have significant radiation dose. CONCLUSION:
      Endovascular management of intracranial dural arteriovenous fistulas with direct
      venous cortical drainage by trans-arterial Onyx embolisation is a safe and
      effective treatment according to our experience. Fluoroscopy times and radiation
      dose may be a concern.

PMID- 19378711
TI  - Early ischemic stroke presentation in Pakistan.
AB  - INTRODUCTION: There are no studies from Pakistan that describe stroke
      presentation rates or factors associated with early or delayed presentation. This
      is important to know because current clinical protocols limit the use of
      recombinant tissue plasminogen activator (rtPA), the only available therapy for
      acute ischemic stroke, to a three-hour window from symptom onset. METHODS: All
      patients aged 14 years or above with acute ischemic stroke of < or = 48 hours
      duration were prospectively identified from the Aga Khan University Stroke Data
      Bank over a 22-month period ending May 2001. RESULTS: 269 ischemic stroke
      patients presented within 48 hours of stroke onset. 55 out of 269 (21%) presented
      within first three hours and 110 out of 269 (41%) within first six hours.
      Unawareness of treatment options (p < 0.001) and inappropriate diagnosis and
      field triage (p = 0.005) were associated with delayed presentation. Small vessel
      occlusion or lacunar stroke in the TOAST (Trial of ORG 10172 in Acute Stroke
      Treatment) ischemic stroke subtype was associated with delayed presentation (p =
      0.047) and cardioembolic stroke was associated with earlier presentation (p =
      0.048). Stroke severity assessed with the National Institutes of Health Stroke
      Scale at a cut off score of > or = 15 was not associated with earlier time to
      presentation at three hours (p = 0.114) but there was some tendency at six hours
      (p = 0.097). CONCLUSIONS: The rate of early stroke presentation in a Pakistani
      tertiary care facility is comparable to certain developed countries. To increase
      the proportion of patients who can benefit from thrombolytic therapy, programs
      need to be instituted to increase public awareness of treatment options for
      stroke and expedited referral by the primary care provider.

PMID- 19378712
TI  - Selective amygdalohippocampectomy: surgical outcome in children versus adults.
AB  - INTRODUCTION: The objective of the study was to review our experience with
      selective amygdalohippocampectomy (SAH) in children and adults with intractable
      temporal lobe epilepsy. METHODS: A retrospective case series was used in the
      setting of a tertiary care hospital which provides epilepsy care to both children
      and adults. All patients underwent a selective amygdalohippocampectomy procedure
      and had at least one year of follow-up. Adults and children were divided into two
      groups and the data was compared between children and adults. RESULTS: Twenty
      three patients, 9 children and 14 adults were studied. Age of surgery varied from
      6 to 58 years. Surgical outcome was variable between the two groups. Amongst the
      children, three patients (33%) were seizure-free (Engel Class I), two patients
      (22%) had rare seizures (Engel Class II), one patient (11%) had a worthwhile
      decrease in seizures (Engel class III) and three patients (32%) had refractory
      seizures that required re-operation with an anterior temporal lobectomy. This
      differed from the adults, who all had a good outcome. Ten patients (71%) were
      seizure-free (Engel Class I) and the remainder (29%) had rare seizures (Engel
      Class II). CONCLUSION: Selective amygdalohippocampectomy can lead to excellent
      seizure surgical outcome in adults with refractory temporal lobe epilepsy.
      However, preliminary results show less favorable results in children. The
      difference is probably related to the different pathology between the two groups.
      Anterior temporal lobe resection may prove to be a more successful operation than
      SAH in children with intractable temporal lobe epilepsy.

PMID- 19378713
TI  - Is temperature regulation different in children susceptible to febrile seizures?
AB  - OBJECTIVE: To examine the relationship between the presence and magnitude of
      fever and susceptibility to febrile seizures, defined as a known family history
      of febrile seizures. METHODS: Reanalysis of a case-control study dataset (Am J
      Dis Child. 1993; 147: 35-39). The magnitude of presenting fever was examined
      between the incident febrile seizure group (N = 75) and febrile control group (N
      = 150) for a family history of febrile seizures. The presence of fever was
      examined between the febrile control group (N = 150) and the afebrile control
      group (N = 150) for a family history of febrile seizures. RESULTS: Children with
      incident febrile seizures had a higher temperature in the emergency department
      than febrile controls (39.3 degrees C vs 39.0 degrees C, p = .004). Febrile
      control children with a known family history of febrile seizures had higher
      temperatures than those without a known family history (39.5 degrees C vs 38.9
      degrees C, p = .04). A model of fever magnitude within the febrile group
      (seizures and controls) suggested that most of this relationship was on the basis
      of family history of febrile seizures rather than seizure or control status, with
      a possibility of interaction. Within the control children (febrile and afebrile),
      a known family history of febrile seizures was associated with fever (OR 3.4, 95%
      CI: 1.1,10.7). CONCLUSIONS: Children susceptible to febrile seizures through a
      known family history of febrile seizures appear more likely to present to
      emergency departments with fever, and when compared to their febrile
      counterparts, a fever of higher magnitude. This data supports Rantala's assertion
      "It may be that regulation of temperature is different in children susceptible to
      febrile seizures".

PMID- 19378714
TI  - Lumbar discectomy: a national survey of neurosurgeons and literature review.
AB  - BACKGROUND: To ascertain neurosurgical practices in the surgical management of
      one-level lumbar discectomies in the Canadian adult population. METHODS: One page
      questionnaire faxed to each Neurosurgeon in Canada with questions relating to
      their practice in the management of this common neurosurgical procedure. All data
      analyzed using Chi-square statistics. RESULTS: 112 completed surveys were
      returned hence, giving a 64% response rate with the respondents being
      predominantly adult neurosurgeons. Of the respondents, 88% perform lumbar
      discectomy in adults. Only 15% of respondents had a Spine Fellowship. For
      preoperative imaging, 44% use BOTH CT and MRI whereas 28% use only MRI and 15%
      use only CT. Prior to initial skin incision, 57% use a localization X-ray image.
      Preoperative antibiotics are prescribed by 92% of respondents. Majority of
      respondents (60%) use a pre-incision local anesthetic, whereas only a minority
      (44%) of respondents employ pre-closure intramuscular injection. With respect to
      magnification, 70% use microscope, 19% loupes, and 8% neither. Only 12% use
      minimally invasive tubular retractors. 68% remove "as much disc as possible",
      while 31% remove "ONLY herniated part". In the case of dural tears, 77% of
      respondents use fibrin glue (Tisseel). Prior to skin closure, majority of
      neurosurgeons do NOT use a fat graft (72%), whereas 61% of respondents use
      epidural steroids. With respect to discharge from the hospital, 58% are
      discharged on the next day, 18% on the same day, and 23% in two days. Return to
      work is not recommended until at least six weeks post-op (96%). Most
      neurosurgeons (93%) would not operate on an individual with a chief complaint of
      low back pain. CONCLUSIONS: Our survey has identified variations in practice
      patterns amongst Canadian Neurosurgeons with respect to performing one-level
      lumbar discectomies. This survey is expected to form a basis for the design of a
      randomized controlled trial in the evaluation of the best management approach for
      this common neurosurgical procedure.

PMID- 19378715
TI  - Percutaneous muscle biopsies: review of 900 consecutive cases at London Health
      Sciences Centre.
AB  - OBJECTIVE: In the present study we review our experience with 900 consecutive
      percutaneous muscle biopsies over the period 1993 to 2007. We examined the
      advantages and limitations of the procedure, biopsy site preferences, diagnostic
      range, frequency of diagnoses and quality of histopathology. Demographics,
      referral patterns and patients' perceptions of the procedure were also assessed.
      METHODS: Cases were identified through the London Health Sciences Centre
      Department of Pathology database. Standard biopsy procedures were followed using
      a manual trocar style instrument. With a neuropathology technologist in
      attendance at all biopsies, biopsies were oriented in the fresh state and snap
      frozen. RESULTS: Most referrals for muscle biopsy were from neuromuscular
      neurologists. The procedure was found to be efficient, well-tolerated and
      produced high quality specimens in all diagnostic categories. No major
      complications occurred. Failure to obtain an adequate tissue sample, although
      uncommon (< 2%), was usually due to marked obesity, edema or muscle wasting.
      Bleeding at the site was rarely problematic and no wound infections were
      reported. CONCLUSIONS: Needle muscle biopsies represent an efficient alternative
      to open biopsies when peripheral nerve sampling is not required and when large
      tissue samples are not needed for extensive biochemical analyses.

PMID- 19378716
TI  - Concussion in hockey: compliance with return to play advice and follow-up status.
AB  - OBJECTIVES: To determine the compliance rate among hockey players with concussion
      or other head injuries who were advised by a physician about return to play. To
      assess compliance of hockey players with return to play advice and to assess the
      incidence of long-term post-concussion symptoms. METHODS: A retrospective chart
      review, telephone questionnaire and follow-up analysis of income, level of
      education and professional aspirations. The study examined 40 hockey players with
      concussion or other head injury treated at a neurosurgical ambulatory clinic, who
      had initial visits between 1995 and 2003, and had been seen at least two years
      prior to completing the questionnaire. RESULTS: There was a 58% (23 of 40)
      participation rate in the study. Fifteen (65%) of the 23 participants were
      advised to never return to play, and 5 (33%) were non-compliant and returned to
      play. Four (80%) of the five noncompliant players continued to suffer from post
      concussion symptoms. Overall, 15 (65%) of the 23 players participating in the
      study continued to suffer post concussion symptoms at least two years after the
      clinic visit. CONCLUSIONS: Five (33%) of 15 hockey players advised to never
      return to play were non-compliant and returned to play, and four continued to
      suffer from post concussion symptoms two or more years later. After repeated
      concussions, 65% of hockey players had long-term sequelae that prevented return
      to play and produced long-term post-concussion symptoms.

PMID- 19378717
TI  - High dose oral steroids commonly used to treat relapses in Canadian MS clinics.
AB  - BACKGROUND: Glucocorticoid treatment improves the speed of functional recovery of
      acute multiple sclerosis (MS) relapses but has not been shown to provide any long
      term functional benefit. There is currently no convincing evidence that the
      clinical benefit is influenced by the route of administration or the dosage of
      glucocorticoid, or the particular glucocorticoid prescribed. Recent studies
      support similarities in the bioequivalence and in the clinical effect of high
      dose oral corticosteroids for MS relapses. OBJECTIVE: This survey aimed to
      determine the relapse treatment preferences of clinicians in Canadian MS clinics.
      METHODS: Members of the Canadian Network of MS Clinics are linked by an email
      server. A one page survey was distributed to the group to determine and report
      use of corticosteroids to manage MS relapses amongst Canadian MS specialists.
      RESULTS: Fifty-one clinicians from 17 MS clinics were surveyed. 32 (63%) surveys
      were returned representing 16 clinics. Five doses are most commonly prescribed,
      usually without a taper. Three or four doses and the use of a corticosteroid
      taper, however, are not uncommon. Gastric cytoprotection and sedatives are often
      prescribed for use as needed. CONCLUSION: This survey illustrates that when
      Canadian clinicians with expertise in managing MS treat MS relapses they choose
      high dose corticosteroids, either oral or i.v. The results therefore represent
      Canadian practice as these clinicians provide direct patient care and influence
      care by community neurologists. Until evidence clearly identifies a superior
      practice all options should be available to clinicians and their patients.

PMID- 19378718
TI  - Migraine: prevalence and associated disability among Nigerian undergraduates.
AB  - BACKGROUND: Studies on migraine in Nigeria are scanty while the disability
      associated with the disease has not been determined. We aimed at determining the
      lifetime prevalence of migraine and its associated disability among the students
      of a Nigerian university. METHOD: Using a multi-stage sampling method,
      undergraduates of Ambrose Alli University, Nigeria were screened with the
      International Headache Society (IHS) criteria. Those who satisfied the criteria
      for migraine were then assessed with the Migraine Disability Assessment
      questionnaire to ascertain the level of disability resulting from migraine in the
      three months preceding the study. Information was also obtained on the use of
      preventive and abortive medications. RESULTS: Out of the 1513 respondents
      screened, 145 satisfied the IHS criteria for the diagnosis of migraine giving an
      overall lifetime prevalence of 9.6% (females 10.3%, males 8.9%, p > 0.05).
      Migraine associated disability was little or none in 53.1% (males 55.2%, females
      51.3%, p > 0.05), mild in 10.3% (males 11.9%, females 9.0%, p > 0.05), moderate
      in 20.7% (males 20.9%, females 20.5%, p > 0.05) and severe in 15.9% (males 11.9%,
      females 19.2%, p > 0.05). In spite of the fact that 53 (36.6%) of the migraineurs
      had moderate-severe disability, only 19/53 (35.8%) reported being on preventive
      treatment while none had ever used a triptan. CONCLUSION: Prevalence of migraine
      among our respondents falls within the range reported from similar studies among
      university students outside Africa. In spite of the high disability associated
      with the disease, use of effective preventive and abortive therapies is very
      poor.

PMID- 19378719
TI  - Neuroleptic-induced tardive cervical dystonia: clinical series of 20 patients.
AB  - BACKGROUND: Cervical dystonia (CD) may be classified according to the underlying
      cause into primary or secondary CD. Previous exposure to neuroleptics is one of
      the main causes of adult-onset secondary dystonia. There are few reports that
      characterize the clinical features of primary CD and secondary neuroleptic
      induced CD. Herein our aim was to investigate a series of patients with
      neuroleptic induced tardive CD and to describe their clinical and demographic
      features. PATIENTS AND METHODS: We retrospectively evaluated 20 patients with
      neuroleptic-induced tardive CD and compared clinical, demographic and therapeutic
      characteristics to another 77 patients with primary CD. All patients underwent
      Botulinum toxin type-A therapy. RESULTS: We did not identify any relevant
      clinical and demographic characteristics in our group of patients that could be
      used to distinguish tardive and primary CD. CONCLUSION: Patients with tardive CD
      presented demographic characteristics and disease course similar to those with
      primary CD.

PMID- 19378720
TI  - Precentral knob corresponds to the primary motor and premotor area.
AB  - PURPOSE: Cortical mapping during awake surgery assesses intraoperative
      neurological change in response to electrical stimulation to provide direct
      information regarding the anatomical localization of the primary motor area (M1).
      The goal of the present study was to analyze the reliability of the
      identification of the precentral knob in the axial image of magnetic resonance
      imaging or functional MRI (fMRI) for the detection of M1. MATERIALS AND METHODS:
      Among patients with brain tumors within or near M1 in whom awake surgery was
      employed from April 2004 through March 2007, 14 cases were analyzed in which
      either the M1 or premotor area (PMA) was successfully detected by mapping during
      awake surgery. RESULTS: The precentral knob was localized to the PMA in 4 cases
      and to M1 in 10 cases. By contrast, the gyrus activated by hand clenching in fMRI
      on the affected side at least partially corresponded to M1 in all cases, while
      those on the unaffected side corresponded to M1 in 12 of 12 cases. CONCLUSION:
      These results indicate that the precentral knob corresponds to PMA as well as to
      M1, whereas the gyrus activated in fMRI corresponds to M1 on the affected and
      unaffected side.

PMID- 19378721
TI  - Resiniferatoxin mediated ablation of TRPV1+ neurons removes TRPA1 as well.
AB  - OBJECTIVES: Resiniferatoxin, the most potent agonist of inflammatory
      pain/vanilloid receptor/cation channel (TRPV1) can be used for neuron subtype
      specific ablation of pain generating cells at the level of the peripheral nervous
      system by Ca(2+)-excytotoxicity. Molecular neurosurgery is an emerging technology
      either to alleviate severe pain in cancer or treat/prevent different local
      neuropathies. Our aim was determining sensory modalities that may be lost after
      resiniferatoxin treatment. METHODS: Newborn or adult mice were treated with
      resiniferatoxin, then changes in chemical and heat sensitivity were correlated
      with alterations of the cell composition of sensory ganglions. RESULTS: Only mice
      treated at adult age became less sensitive to heat stimuli, while both treatment
      groups lost sensitivity to specific vanilloid agonists of TRPV1 and,
      interestingly, to allyl-isothiocyanate, a selective agonist of TRPA1. Our in vivo
      and post mortem analytical results confirmed that TRPV1 and TRPA1 function
      together and resiniferatoxin-mediated neurosurgery removes both sensor molecules.
      DISCUSSION: In adult mice resiniferatoxin causes: i) desensitization to heat and
      ii) sensitization to cold. Cold hyperalgesia, an imbalance in thermosensation,
      might be conferred by a prominent cold receptor that is expressed in surviving
      resiniferatoxin-resistant sensory neurons and compensates for pain signals lost
      with TRPA1 and TRPV1 double positive cells in the peripheral nervous system.

PMID- 19378722
TI  - Cerebral proliferative angiopathy.

PMID- 19378723
TI  - Cerebral schistosomiasis--an unusual presentation of an intracranial mass lesion.

PMID- 19378724
TI  - In-stent stenosis following covered stent-graft placement.

PMID- 19378725
TI  - Intracranial hypotension causing reversible frontotemporal dementia and coma.

PMID- 19378726
TI  - Extradural middle fossa approach to a clear cell meningioma in a child.

PMID- 19378727
TI  - Cranial nerve palsies associated with influenza B.

PMID- 19378728
TI  - Point/Counterpoint. Intensity modulated electronic brachytherapy will soon become
      the brachytherapy treatment of choice for irregularly shaped tumor cavities or
      those closely bounded by critical structures.

PMID- 19378729
TI  - Radiotherapy margin design with particular consideration of high curvature CTVs.
AB  - In applying 3D conformal radiation therapy to a tumor clinical target volume
      (CTV), a margin is added around the CTV to account for any sources of error in
      the application of treatment which may result in misalignment between the CTV and
      the dose distribution actually delivered. The volume enclosed within the CTV plus
      the margin is known as the PTV, or planning target volume. The larger the errors
      are anticipated to be, the wider the margin will need to be to accommodate those
      errors. Based on the approach of van Herk et al. ["The probability of correct
      target dosage: Dose-population histograms for deriving treatment margins in
      radiotherapy," Int. J. Radiat. Oncol. Biol., Phys. 47(4), 1121-1135 (2000)] this
      paper develops the mathematical theory behind the calculation of the margin width
      required to ensure that the entire CTV receives sufficiently high dose with
      sufficiently high probability. The margin recipe developed not only considers the
      magnitude of the errors but also includes a term to adjust for curved CTV
      surfaces. In doing so, the accuracy of the margin recipe is enhanced yet remains
      mathematically concise enough to be readily implemented in the clinical setting.
      The results are particularly relevant for clinical situations in which the
      uncertainties in treatment are large relative to the size of the CTV.

PMID- 19378730
TI  - Determination of electron energy, spectral width, and beam divergence at the exit
      window for clinical megavoltage x-ray beams.
AB  - Monte Carlo simulations of x-ray beams typically take parameters of the electron
      beam in the accelerating waveguide to be free parameters. In this paper, a
      methodology is proposed and implemented to determine the energy, spectral width,
      and beam divergence of the electron source. All treatment head components were
      removed from the beam path, leaving only the exit window. With the x-ray target
      and flattener out of the beam, uncertainties in physical characteristics and
      relative position of the target and flattening filter, and in spot size, did not
      contribute to uncertainty in the energy. Beam current was lowered to reduce
      recombination effects. The measured dose distributions were compared with Monte
      Carlo simulation of the electron beam through the treatment head to extract the
      electron source characteristics. For the nominal 6 and 18 MV x-ray beams, the
      energies were 6.51 +/- 0.15 and 13.9 +/- 0.2 MeV, respectively, with the
      uncertainties resulting from uncertainties in the detector position in the
      measurement and in the stopping power in the simulations. Gaussian spectral
      distributions were used, with full widths at half maximum ranging from 20 +/- 4%
      at 6 MV to 13 +/- 4% at 18 MV required to match the fall-off portion of the
      percent-depth ionization curve. Profiles at the depth of maximum dose from
      simulations that used the manufacturer-specified exit window geometry and no beam
      divergence were 2-3 cm narrower than measured profiles. Two simulation
      configurations yielding the measured profile width were the manufacturer
      specified exit window thickness with electron source divergences of 3.3 degrees
      at 6 MV and 1.8 degrees at 18 MV and an exit window 40% thicker than the
      manufacturer's specification with no beam divergence. With the x-ray target in
      place (and no flattener), comparison of measured to simulated profiles sets upper
      limits on the electron source divergences of 0.2 degrees at 6 MV and 0.1 degrees
      at 18 MV. A method of determining source characteristics without mechanical
      modification of the treatment head, and therefore feasible in clinics, is
      presented. The energies and spectral widths determined using this method agree
      with those determined with only the exit window in the beam path.

PMID- 19378731
TI  - Characterization of a fiber-coupled Al2O3:C luminescence dosimetry system for
      online in vivo dose verification during 192Ir brachytherapy.
AB  - A prototype of a new dose-verification system has been developed to facilitate
      prevention and identification of dose delivery errors in remotely afterloaded
      brachytherapy. The system allows for automatic online in vivo dosimetry directly
      in the tumor region using small passive detector probes that fit into applicators
      such as standard needles or catheters. The system measures the absorbed dose rate
      (0.1 s time resolution) and total absorbed dose on the basis of radioluminescence
      (RL) and optically stimulated luminescence (OSL) from aluminum oxide crystals
      attached to optical fiber cables (1 mm outer diameter). The system was tested in
      the range from 0 to 4 Gy using a solid-water phantom, a Varian GammaMed Plus
      192Ir PDR afterloader, and dosimetry probes inserted into stainless-steel
      brachytherapy needles. The calibrated system was found to be linear in the tested
      dose range. The reproducibility (one standard deviation) for RL and OSL
      measurements was 1.3%. The measured depth-dose profiles agreed well with the
      theoretical expectations computed with the EGSNRC Monte Carlo code, suggesting
      that the energy dependence for the dosimeter probes (relative to water) is less
      than 6% for source-to-probe distances in the range of 2-50 mm. Under certain
      conditions, the RL signal could be greatly disturbed by the so-called stem signal
      (i.e., unwanted light generated in the fiber cable upon irradiation). The OSL
      signal is not subject to this source of error. The tested system appears to be
      adequate for in vivo brachytherapy dosimetry.

PMID- 19378732
TI  - A noninvasive eye fixation monitoring system for CyberKnife radiotherapy of
      choroidal and orbital tumors.
AB  - A new noninvasive monitoring system for fixing the eye has been developed to
      treat orbital and choroidal tumors with CyberKnife-based radiotherapy. This
      device monitors the eye during CT/MRI scanning and during treatment. The results
      of this study demonstrate the feasibility of the fixation light system for
      CyberKnife-based treatments of orbital and choroidal tumors and supports the idea
      that larger choroidal melanomas and choroidal metastases could be treated with
      CyberKnife without implanting fiducial markers.

PMID- 19378733
TI  - Biological equivalent dose studies for dose escalation in the stereotactic
      synchrotron radiation therapy clinical trials.
AB  - Synchrotron radiation is an innovative tool for the treatment of brain tumors. In
      the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose
      enhancement specific to the tumor is obtained. The tumor is loaded with a high
      atomic number (Z) element and it is irradiated in stereotactic conditions from
      several entrance angles. The aim of this work was to assess dosimetric properties
      of the SSRT for preparing clinical trials at the European Synchrotron Radiation
      Facility (ESRF). To estimate the possible risks, the doses received by the tumor
      and healthy tissues in the future clinical conditions have been calculated by
      using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have
      been determined for different iodine concentrations in the tumor, several tumor
      positions, tumor sizes, and different beam sizes. A scheme for the dose
      escalation in the various phases of the clinical trials has been proposed. The
      biological equivalent doses and the normalized total doses received by the skull
      have been calculated in order to assure that the tolerance values are not
      reached.

PMID- 19378734
TI  - Integral dose conservation in radiotherapy.
AB  - Treatment planners frequently modify beam arrangements and use IMRT to improve
      target dose coverage while satisfying dose constraints on normal tissues. The
      authors herein analyze the limitations of these strategies and quantitatively
      assess the extent to which dose can be redistributed within the patient volume.
      Specifically, the authors hypothesize that (1) the normalized integral dose is
      constant across concentric shells of normal tissue surrounding the target
      (normalized to the average integral shell dose), (2) the normalized integral
      shell dose is constant across plans with different numbers and orientations of
      beams, and (3) the normalized integral shell dose is constant across plans when
      reducing the dose to a critical structure. Using the images of seven patients
      previously irradiated for cancer of brain or prostate cancer and one idealized
      scenario, competing three-dimensional conformal and IMRT plans were generated
      using different beam configurations. Within a given plan and for competing plans
      with a constant mean target dose, the normalized integral doses within concentric
      "shells" of surrounding normal tissue were quantitatively compared. Within each
      patient, the normalized integral dose to shells of normal tissue surrounding the
      target was relatively constant (1). Similarly, for each clinical scenario, the
      normalized integral dose for a given shell was also relatively constant
      regardless of the number and orientation of beams (2) or degree of sparing of a
      critical structure (3). 3D and IMRT planning tools can redistribute, rather than
      eliminate dose to the surrounding normal tissues (intuitively known by planners).
      More specifically, dose cannot be moved between shells surrounding the target but
      only within a shell. This implies that there are limitations in the extent to
      which a critical structure can be spared based on the location and geometry of
      the critical structure relative to the target.

PMID- 19378735
TI  - Noise suppression in scatter correction for cone-beam CT.
AB  - Scatter correction is crucial to the quality of reconstructed images in x-ray
      cone-beam computed tomography (CBCT). Most of existing scatter correction methods
      assume smooth scatter distributions. The high-frequency scatter noise remains in
      the projection images even after a perfect scatter correction. In this paper,
      using a clinical CBCT system and a measurement-based scatter correction, the
      authors show that a scatter correction alone does not provide satisfactory image
      quality and the loss of the contrast-to-noise ratio (CNR) of the scatter
      corrected image may overwrite the benefit of scatter removal. To circumvent the
      problem and truly gain from scatter correction, an effective scatter noise
      suppression method must be in place. They analyze the noise properties in the
      projections after scatter correction and propose to use a penalized weighted
      least-squares (PWLS) algorithm to reduce the noise in the reconstructed images.
      Experimental results on an evaluation phantom (Catphan600) show that the proposed
      algorithm further reduces the reconstruction error in a scatter corrected image
      from 10.6% to 1.7% and increases the CNR by a factor of 3.6. Significant image
      quality improvement is also shown in the results on an anthropomorphic phantom,
      in which the global noise level is reduced and the local streaking artifacts
      around bones are suppressed.

PMID- 19378736
TI  - Autoregressive moving average modeling for spectral parameter estimation from a
      multigradient echo chemical shift acquisition.
AB  - The authors investigated the performance of the iterative Steiglitz-McBride (SM)
      algorithm on an autoregressive moving average (ARMA) model of signals from a
      fast, sparsely sampled, multiecho, chemical shift imaging (CSI) acquisition using
      simulation, phantom, ex vivo, and in vivo experiments with a focus on its
      potential usage in magnetic resonance (MR)-guided interventions. The ARMA signal
      model facilitated a rapid calculation of the chemical shift, apparent spin-spin
      relaxation time (T2*), and complex amplitudes of a multipeak system from a
      limited number of echoes (< or equal 16). Numerical simulations of one- and two
      peak systems were used to assess the accuracy and uncertainty in the calculated
      spectral parameters as a function of acquisition and tissue parameters. The
      measured uncertainties from simulation were compared to the theoretical Cramer
      Rao lower bound (CRLB) for the acquisition. Measurements made in phantoms were
      used to validate the T2* estimates and to validate uncertainty estimates made
      from the CRLB. We demonstrated application to real-time MR-guided interventions
      ex vivo by using the technique to monitor a percutaneous ethanol injection into a
      bovine liver and in vivo to monitor a laser-induced thermal therapy treatment in
      a canine brain. Simulation results showed that the chemical shift and amplitude
      uncertainties reached their respective CRLB at a signal-to-noise ratio (SNR) > or
      =5 for echo train lengths (ETLs) > or =4 using a fixed echo spacing of 3.3 ms.
      T2* estimates from the signal model possessed higher uncertainties but reached
      the CRLB at larger SNRs and/or ETLs. Highly accurate estimates for the chemical
      shift (<0.01 ppm) and amplitude (<1.0%) were obtained with > or =4 echoes and for
      T2*(<1.0%) with > or =7 echoes. We conclude that, over a reasonable range of SNR,
      the SM algorithm is a robust estimator of spectral parameters from fast CSI
      acquisitions that acquire < or =16 echoes for one- and two-peak systems.
      Preliminary ex vivo and in vivo experiments corroborated the results from
      simulation experiments and further indicate the potential of this technique for
      MR-guided interventional procedures with high spatiotemporal resolution
      approximately 1.6 x 1.6 x 4 mm3 in < or =5 s.

PMID- 19378737
TI  - Evaluation of clinical image processing algorithms used in digital mammography.
AB  - Screening is the only proven approach to reduce the mortality of breast cancer,
      but significant numbers of breast cancers remain undetected even when all quality
      assurance guidelines are implemented. With the increasing adoption of digital
      mammography systems, image processing may be a key factor in the imaging chain.
      Although to our knowledge statistically significant effects of manufacturer
      recommended image processings have not been previously demonstrated, the
      subjective experience of our radiologists, that the apparent image quality can
      vary considerably between different algorithms, motivated this study. This
      article addresses the impact of five such algorithms on the detection of clusters
      of microcalcifications. A database of unprocessed (raw) images of 200 normal
      digital mammograms, acquired with the Siemens Novation DR, was collected
      retrospectively. Realistic simulated microcalcification clusters were inserted in
      half of the unprocessed images. All unprocessed images were subsequently
      processed with five manufacturer-recommended image processing algorithms (Agfa
      Musica 1, IMS Raffaello Mammo 1.2, Sectra Mamea AB Sigmoid, Siemens OPVIEW v2,
      and Siemens OPVIEW v1). Four breast imaging radiologists were asked to locate and
      score the clusters in each image on a five point rating scale. The free-response
      data were analyzed by the jackknife free-response receiver operating
      characteristic (JAFROC) method and, for comparison, also with the receiver
      operating characteristic (ROC) method. JAFROC analysis revealed highly
      significant differences between the image processings (F = 8.51, p < 0.0001),
      suggesting that image processing strongly impacts the detectability of clusters.
      Siemens OPVIEW2 and Siemens OPVIEW1 yielded the highest and lowest performances,
      respectively. ROC analysis of the data also revealed significant differences
      between the processing but at lower significance (F = 3.47, p = 0.0305) than
      JAFROC. Both statistical analysis methods revealed that the same six pairs of
      modalities were significantly different, but the JAFROC confidence intervals were
      about 32% smaller than ROC confidence intervals. This study shows that image
      processing has a significant impact on the detection of microcalcifications in
      digital mammograms. Objective measurements, such as described here, should be
      used by the manufacturers to select the optimal image processing algorithm.

PMID- 19378738
TI  - A detailed radiobiological and dosimetric analysis of biochemical outcomes in a
      case-control study of permanent prostate brachytherapy patients.
AB  - The purpose of this study is to determine dosimetric and radiobiological
      predictors of biochemical control after recalculation of prostate implant
      dosimetry using updated AAPM Task Group 43 (TG-43) parameters and the
      radiobiological parameters recommended by TG-137. All biochemical failures among
      patients implanted with 125I Or 103Pd sources between 1994 and March 2006 were
      matched 2:1 with nonfailure controls. The individual matching was by risk group,
      radionuclide, prescribed dose, and time of implant (one match before and one
      after the failed patient) resulting in a median follow-up of 10.9 years. Complete
      dose volume histogram (DVH) data were recalculated for all 55 cases and 110
      controls after updating the original source strength by the retrospectively
      determined ratios of TG-43. Differential DVH data were acquired in 179 increments
      of prostate volume versus percentage prescribed dose. At each incremental dose
      level i, the biologically equivalent dose BEDi, equivalent uniform dose EUDi, and
      tumor control probability TCPi were calculated from the implant dose plus any
      external beam delivered to the patient. Total BED, EUD, and TCP were then derived
      from the incremental values for comparison with single point dosimetric quality
      parameters and DVH-based averages. There was no significant difference between
      failures and controls in terms of total BED (143 vs 142 Gy), EUD (95 vs 94 Gy),
      or TCP (0.87 vs 0.89). Conditional logistic regression analysis factored out the
      matching variables and stratified the cohort into each case and its controls, but
      no radiobiological parameter was predictive of biochemical failure. However,
      there was a significant difference between radiobiological parameters of 125I and
      103Pd due to less complete coverage of the target volume by the former isotope.
      The implant BED and TCP were highly correlated with the D90 and natural
      prescription doses and a series of mean DVH-based doses such as the harmonic mean
      and expressions of the generalized EUD. In this case-control study of prostate
      brachytherapy biochemical failures and nonfailures, there were no radiobiological
      parameters derived from detailed DVH-based analysis that predicted for
      biochemical control. This may indicate that in our approach, implant dosimetry is
      at or near the limits of clinically effective dose escalation.

PMID- 19378739
TI  - Simulated scatter performance of an inverse-geometry dedicated breast CT system.
AB  - The purpose of this work was to quantify the effects of scatter for inverse
      geometry dedicated breast CT compared to cone-beam breast CT through simulations.
      The inverse geometry was previously proposed as an alternative to cone-beam
      acquisition for volumetric CT. The inverse geometry consists of a large-area
      scanned-source opposite a detector array that is smaller in the transverse
      direction. While the gantry rotates, the x-ray beam is rapidly sequenced through
      an array of positions, acquiring a truncated projection image at each position.
      Inverse-geometry CT (IGCT) is expected to detect less scatter than cone-beam
      methods because only a fraction of the object is irradiated at any time and the
      fast detector isolates the measurements from sequential x-ray beams. An
      additional scatter benefit is the increased air gap due to the inverted geometry.
      In this study, we modeled inverse-geometry and cone-beam dedicated breast CT
      systems of equivalent resolution, field of view, and photon fluence. Monte Carlo
      simulations generated scatter and primary projections of three cylindrical
      phantoms of diameters 10, 14, and 18 cm composed of 50% adipose/50% glandular
      tissue. The scatter-to-primary ratio (SPR) was calculated for each breast
      diameter. Monte Carlo simulations were combined with analytical simulations to
      generate inverse-geometry and cone-beam images of breast phantoms embedded with
      tumors. Noise reprehenting the photon fluence of a realistic breast CT scan was
      added to the simulated projections. Cone-beam data were reconstructed with and
      without an ideal scatter correction. The CNR between breast tumor and background
      was compared for the inverse and cone-beam geometries for the three phantom
      diameters. Results demonstrated an order of magnitude reduction in SPR for the
      IGCT system compared to the cone-beam system. For example, the peak IGCT SPRs
      were 0.05 and 0.09 for the 14 and 18 cm phantoms, respectively, compared to 0.42
      and 1 for the cone-beam system. For both geometries, the effects of scatter on
      contrast-to-noise ratio (CNR) were small for the 10 cm diameter phantom. The
      inverse-geometry improved the CNR by factors of 1.16 for the 14 cm phantom and
      1.48 for the 18 cm phantom compared to a cone-beam acquisition without scatter
      correction. When an ideal scatter correction was applied to the cone-beam
      acquisition, the IGCT CNR improvements were 1.03 and 1.25 for the 14 and 18 cm
      phantoms. Overall, the results suggest that the inverse geometry may be
      advantageous for dedicated breast CT, an application that requires high-contrast
      resolution, spatial resolution, and dose efficiency.

PMID- 19378740
TI  - The delta envelope: a technique for dose distribution comparison.
AB  - The gamma index is a tool that compares a dose distribution with a reference
      distribution by combining dose-difference and distance-to-agreement criteria. It
      has been widely used for ten years despite its high computational cost. This cost
      is due to both a search process for each reference point and the necessity to
      remove overestimations caused by the discrete nature of dose grids. The method
      proposed in this paper is much faster since it avoids both these problems. It
      consists in computing the delta envelope formed by the gamma ellipsoids around
      the points of the reference distribution. This delta envelope provides dose
      difference tolerances that are then used to create new indices, called the delta
      indices, that provide useful information to interpret the deviations. Applied to
      both 1D and 2D test cases and compared to the gamma index, the S indices proved
      to be very accurate and intuitive. Their computational efficiency was evaluated
      on a 3D case: the delta envelope can be computed in 8 s on a 250 x 250 x 50 grid.
      Moreover it can be precomputed if the reference dose is known in advance. Then
      the delta indices are obtained in less than 2 s.

PMID- 19378741
TI  - Monte Carlo simulations and radiation dosimetry measurements of peripherally
      applied HDR 192Ir breast brachytherapy D-shaped applicators.
AB  - Conformal dose coverage for accelerated partial breast irradiation or
      radiotherapy boost can be obtained with AccuBoost D-shaped brachytherapy
      applicators using a flattened surface positioned near the patient. Three D-shaped
      applicators (D45/D53/D60) were dosimetrically characterized using Monte Carlo
      methods (MCNP5), air ionization chambers (Farmer and Markus), and radiochromic
      film (GafChromic EBT) in polystyrene and ICRU 44 breast tissue. HDR 192Ir source
      dwell times were either constant or optimized to improve skin dose uniformity.
      Scatter dose decreased as depth decreased. 10 mm beyond the applicator aperture,
      dose reductions of 90% and 51% were observed at depths of 0 and 30 mm,
      respectively. Similarly, planar dose uniformity improved as depth decreased and
      was also due to scatter and applicator geometry. Dose uniformity inside the
      applicator aperture was approximately 11% and 15% for all three applicators at
      the skin and 30 mm deep, respectively. Depth dose measurements in polystyrene
      using ion chamber and radiochromic film agreed with Monte Carlo results within
      2%. Discrepancies between film and Monte Carlo dose profiles at 30 mm depth were
      within 1%.

PMID- 19378742
TI  - Static and rotational output variation of a tomotherapy unit.
AB  - A simple device to check the machine output in rotational mode is described.
      Integral and instantaneous beam output in absolute dose can be measured and
      analyzed in a very simple manner. A method to correlate the results with the
      value obtained during the machine calibration in static beam and the reference
      value used by the treatment planning system for dose calculation in rotation beam
      is also described. Using this method and device, the daily output can be
      performed in rotational conditions which are closer to the treatment conditions.
      Measurement results using this device show differences in the beam output between
      static and rotational delivery which have to be considered carefully during the
      calibration process.

PMID- 19378743
TI  - Evaluation of clip localization for different kilovoltage imaging modalities as
      applied to partial breast irradiation setup.
AB  - Surgical clip localization and image quality were evaluated for different types
      of kilovoltage cone beam imaging modalities as applied to partial breast
      irradiation (PBI) setup. These modalities included (i) clinically available
      radiographs and cone beam CT (CB-CT) and (ii) various alternative modalities
      based on partial/sparse/truncated CB-CT. An anthropomorphic torso-breast phantom
      with surgical clips was used for the imaging studies. The torso phantom had
      artificial lungs, and the attached breast phantom was a mammographic phantom with
      realistic shape and tissue inhomogeneities. Three types of clips of variable size
      were used in two orthogonal orientations to assess their in-/cross-plane
      characteristics for image-guided setup of the torso-breast phantom in supine
      position. All studies were performed with the Varian on-board imaging (OBI,
      Varian) system. CT reconstructions were calculated with the standard Feldkamp
      Davis-Kress algorithm. First, the radiographs were studied for a wide range of
      viewing angles to characterize image quality for various types of body anatomy in
      the foreground/background of the clips. Next, image reconstruction quality was
      evaluated for partial/sparse/truncated CB-CT. Since these modalities led to
      reconstructions with strong artifacts due to insufficient input data, a knowledge
      based CT reconstruction method was also tested. In this method, the input data to
      the reconstruction algorithm were modified by combining complementary data sets
      selected from the treatment and reference projections. Different
      partial/sparse/truncated CB-CT scan types were studied depending on the total are
      angle, angular increment between the consequent views (CT projections),
      orientation of the arc center with respect to the imaged breast and chest wall,
      and imaging field size. The central angles of the viewing arcs were either
      tangential or orthogonal to the chest wall. Several offset positions of the
      phantom with respect to the reference position were studied. The acquired and
      reconstructed image data sets were analyzed using home-built software focusing on
      the ability to localize clips in 3D. Streaking and leakage reconstruction
      artifacts and spatial distortions of breast surface were analyzed as well.
      Advantages and disadvantages of each kilovoltage CB imaging modality as applied
      to partial breast setup evaluation based on clips are presented. Because clips
      were found to be difficult to recognize in radiographs, 3D reconstructions were
      preferred. Even though it was possible to localize clips with about +/-1 mm
      accuracy based on reconstructions for short arcs of 40 degrees and incremental
      angle up to about 5 degrees, identification of clips in such reconstructions is
      difficult. Reconstructions obtained for arcs of as low as 80 degrees and
      incremental angle of as high as 3 degrees were suggested for easier clip
      identification. For more severely undersampled data, iterative CB-CT
      reconstruction is recommended to decrease the artifacts.

PMID- 19378744
TI  - JPEG2000 3D compression vs. 2D compression: an assessment of artifact amount and
      computing time in compressing thin-section abdomen CT images.
AB  - To assess the advantages of the Joint Photographic Experts Group (JPEG)2000 3D
      (part 2) over JPEG2000 in compressing thin-section abdomen CT data sets, 60 thin
      section (0.67 mm) scans from 35 males and 25 females, ranging from 23 to 95 years
      of age (mean, 58 years), were compressed reversibly (as a negative control) and
      irreversibly to 4:1, 6:1, 8:1, 10:1, and 12:1 using JPEG2000 3D and JPEG2000
      algorithms. Encoding and decoding times and peak signal-to-noise ratios (PSNRs)
      were measured. For 60 (one image per scan) representative sections containing
      abnormalities, three radiologists independently compared original and compressed
      images and graded compression artifacts as 0 (none, indistinguishable), 1 (barely
      perceptible), 2 (subtle), or 3 (significant). According to pooled radiologists'
      responses, the range of visually lossless threshold (VLT, the highest compression
      ratio at which a compressed image is indistinguishable from its original) was
      determined as one of <4:1, 4:1-6:1, 6:1-8:1, 8:1-10:1, 10:1-12:1, and >12:1.
      Wilcoxon signed rank tests and exact tests for paired proportions were used for
      the comparisons between the two compressions. At each irreversible compression
      ratio, compared to JPEG2000, JPEG2000 3D required two- or threefold greater
      computing times (p < 0.001) and introduced less artifacts in terms of PSNR (p
      <0.001) and the grade (p < 0.02 at 6:1 or higher) and the presence of perceived
      artifacts (p <0.008, at 6:1 for all readers and at 8:1 for two readers).
      According to PSNR and readers' responses, 6:1 and 8:1 JPEG2000 3D compressions
      showed more artifacts than 4:1 and 6:1 JPEG2000 compressions, respectively, and
      10:1 and 12:1 JPEG2000 3D compressions showed similar artifacts to those of 8:1
      and 10:1 JPEG2000 compressions, respectively. The determined VLT range was higher
      for JPEG2000 3D than for JPEG2000 (p < 0.001): the 3D compression showed the VLT
      ranges of 4:1-6:1, 6:1-8:1, and 8:1-10:1 for 24 (40%), 30 (50%), and 6 (10%) of
      the 60 original images, respectively, while the 2D compression showed the VLT
      ranges of <4:1, 4:1-6:1, and 6:1-8:1 for 1 (1.7%), 40 (66.7%), and 19 (31.6%)
      images, respectively. Compared to JPEG2000, JPEG2000 3D increased the VLT range
      in 23 of the 60 original images by one (n=22) or two ranges (n=1), while the
      remaining 37 images had the same VLT range between the two compressions. In
      conclusion, compared to JPEG2000 compression, JPEG2000 3D compression yields less
      artifacts in compressing thin-section abdomen CT images but requires
      significantly greater computing times. For the tested data set compressed to the
      range from 4:1 to 12:1, JPEG2000 3D could increase compression level reasonably
      (by 2 or less in terms of compression ratio) compared to JPEG2000 for the same
      amount of artifacts.

PMID- 19378745
TI  - Design of optimal collimation for dedicated molecular breast imaging systems.
AB  - Molecular breast imaging (MBI) is a functional imaging technique that uses
      specialized small field-of-view gamma cameras to detect the preferential uptake
      of a radiotracer in breast lesions. MBI has potential to be a useful adjunct
      method to screening mammography for the detection of occult breast cancer.
      However, a current limitation of MBI is the high radiation dose (a factor of 7-10
      times that of screening mammography) associated with current technology. The
      purpose of this study was to optimize the gamma camera collimation with the aim
      of improving sensitivity while retaining adequate resolution for the detection of
      sub-10-mm lesions. Square-hole collimators with holes matched to the pixilated
      cadmium zinc telluride detector elements of the MBI system were designed. Data
      from MBI patient studies and parameters of existing dual-head MBI systems were
      used to guide the range of desired collimator resolutions, source-to-collimator
      distances, pixel sizes, and collimator materials that were examined. General
      equations describing collimator performance for a conventional gamma camera were
      used in the design process along with several important adjustments to account
      for the specialized imaging geometry of the MBI system. Both theoretical
      calculations and a Monte Carlo model were used to measure the geometric
      efficiency (or sensitivity) and resolution of each designed collimator. Results
      showed that through optimal collimation, collimator sensitivity could be improved
      by factors of 1.5-3.2, while maintaining a collimator resolution of either < or
      =5 or < or = 7.5 mm at a distance of 3 cm from the collimator face. These gains
      in collimator sensitivity permit an inversely proportional drop in the required
      dose to perform

PMID- 19378746
TI  - Characterization of scatter in cone-beam CT breast imaging: comparison of
      experimental measurements and Monte Carlo simulation.
AB  - It is commonly understood that scattered radiation in x-ray computed tomography
      (CT) degrades the reconstructed image. As a precursor to developing scatter
      compensation methods, it is important to characterize this scatter using both
      empirical measurements and Monte Carlo simulations. Previous studies
      characterizing scatter using both experimental measurements and Monte Carlo
      simulations have been reported in diagnostic radiology and conventional
      mammography. The emerging technology of cone-beam CT breast imaging (CTBI)
      differs significantly from conventional mammography in the breast shape and
      imaging geometry, aspects that are important factors impacting the measured
      scatter. This study used a bench-top cone-beam CTBI system with an indirect flat
      panel detector. A cylindrical phantom with equivalent composition of 50%
      fibroglandular and 50% adipose tissues was used, and scatter distributions were
      measured by beam stop and aperture methods. The GEANT4-based simulation package
      GATE was used to model x-ray photon interactions in the phantom and detector.
      Scatter to primary ratio (SPR) measurements using both the beam stop and aperture
      methods were consistent within 5% after subtraction of nonbreast scatter
      contributions and agree with the low energy electromagnetic model simulation in
      GATE. The validated simulation model was used to characterize the SPR in
      different CTBI conditions. In addition, a realistic, digital breast phantom was
      simulated to determine the characteristics of various scatter components that
      cannot be separated in measurements. The simulation showed that the scatter
      distribution from multiple Compton and Rayleigh scatterings, as well as from the
      single Compton scattering, has predominantly low-frequency characteristics. The
      single Rayleigh scatter was observed to be the primary contribution to the
      spatially variant scatter component.

PMID- 19378747
TI  - Field size effect of radiation quality in carbon therapy using passive method.
AB  - The authors have investigated the dependency of radiation quality and absorbed
      dose on radiation field size in therapeutic carbon beams. The field size of the
      broad beam, formed using the passive technique, was controlled from 20 to 100 mm
      per side with a multileaf collimator. The absorbed dose and radiation quality on
      the beam center were evaluated at several depths in a water phantom using
      microdosimetric technique in experiments and Monte Carlo simulations. With an
      increase in the field size, the radiation quality was reduced, although the
      absorbed dose grew at the center of the field. This indicates that the dose and
      radiation quality at the center of the broad beam are influenced by particles
      from the off-center region via large-angle scattering and that such particles
      have relatively low radiation quality and mainly consist of fragment particles.
      Because such a tendency appeared to be more remarkable in the deeper region of
      the water phantom, it is likely that fragment particles that are born in a water
      phantom have a marked role in determining the field size effect.

PMID- 19378748
TI  - Electromagnetic tracking in the clinical environment.
AB  - When choosing an electromagnetic tracking system (EMTS) for image-guided
      procedures several factors must be taken into consideration. Among others these
      include the system's refresh rate, the number of sensors that need to be tracked,
      the size of the navigated region, the system interaction with the environment,
      whether the sensors can be embedded into the tools and provide the desired
      transformation data, and tracking accuracy and robustness. To date, the only
      factors that have been studied extensively are the accuracy and the
      susceptibility of EMTSs to distortions caused by ferromagnetic materials. In this
      paper the authors shift the focus from analysis of system accuracy and stability
      to the broader set of factors influencing the utility of EMTS in the clinical
      environment. The authors provide an analysis based on all of the factors
      specified above, as assessed in three clinical environments. They evaluate two
      commercial tracking systems, the Aurora system from Northern Digital Inc., and
      the 3D Guidance system with three different field generators from Ascension
      Technology Corp. The authors show that these systems are applicable to specific
      procedures and specific environments, but that currently, no single system
      configuration provides a comprehensive solution across procedures and
      environments.

PMID- 19378749
TI  - Dosimetric evaluations of the interplay effect in respiratory-gated intensity
      modulated radiation therapy.
AB  - The interplay between a mobile target and a dynamic multileaf collimator can
      compromise the accuracy of intensity-modulated radiation therapy (IMRT). Our goal
      in this study is to investigate the dosimetric effects caused by the respiratory
      motion during IMRT. A moving phantom was built to simulate the typical breathing
      motion. Different sizes of the gating windows were selected for gated deliveries.
      The residual motions during the beam-on period ranged from 0.5 to 3 cm. An IMRT
      plan with five treatment fields from different gantry angles were delivered to
      the moving phantom for three irradiation conditions: Stationary condition, moving
      with the use of gating system, and moving without the use of gating system. When
      the residual motion was 3 cm, the results showed significant differences in dose
      distributions between the stationary condition and the moving phantom without
      gating beam control. The overdosed or underdosed areas enclosed about 33% of the
      treatment area. In contrast, the dose distribution on the moving phantom with
      gating window set to 0.5 cm showed no significant differences from the stationary
      phantom. With the appropriate setting of the gating window, the deviation of dose
      from the respiratory motion can be minimized. It appeals that limiting the
      residual motion to less than 0.5 cm is critical for the treatments of mobile
      structures.

PMID- 19378750
TI  - Calculation of the biological effective dose for piecewise defined dose-rate
      fits.
AB  - An algorithmic solution to the biological effective dose (BED) calculation from
      the Lea-Catcheside formula for a piecewise defined function is presented. Data
      from patients treated for metastatic thyroid cancer were used to illustrate the
      solution. The Lea-Catcheside formula for the G-factor of the BED is integrated
      numerically using a large number of small trapezoidal fits to each integral. The
      algorithmically calculated BED is compatible with an analytic calculation for a
      similarly valued exponentially fitted dose-rate plot and is the only resolution
      for piecewise defined dose-rate functions.

PMID- 19378751
TI  - MRI endoscopy using intrinsically localized probes.
AB  - Magnetic resonance imaging (MRI) is traditionally performed with fixed externally
      applied gradient magnetic fields and is hence intrinsically locked to the
      laboratory frame of reference (FoR). Here a method for high-resolution MRI that
      employs active, catheter-based, tiny internal probes that utilize the spatial
      properties of the probe itself for localization is proposed and demonstrated at 3
      T. Because these properties are intrinsic to the probe, they move with it,
      transforming MRI from the laboratory FoR to the FoR of the device itself,
      analogous to an endoscope. The "MRI endoscope" can utilize loop coils and
      loopless antennas with modified sensitivity, in combination with adiabatic
      excitation by the device itself, to restrict the MRI sensitivity to a disk-shaped
      plane a few mm thick. Excitation with the MRI endoscope limits the eddy currents
      induced in the sample to an excited volume whose size is orders of magnitude
      below that excited by a conventional body MRI coil. Heat testing shows maximum
      local temperature increases of <1 degrees C during MRI, within regulatory
      guidelines. The method is demonstrated in a kiwifruit, in intact porcine and
      rabbit aortas, and in an atherosclerotic human iliac artery specimen, with in
      plane resolution as small as 80 microm and 1.5-5 mm slice thickness.

PMID- 19378752
TI  - The effect of scatter and glare on image quality in contrast-enhanced breast
      imaging using an a-Si/CsI(TI) full-field flat panel detector.
AB  - The purpose of this study is to evaluate the performance of an antiscatter grid
      and its potential benefit on image quality for a full-field digital mammography
      (FFDM) detector geometry at energies typical for temporal subtraction contrast
      enhanced (CE) breast imaging. The signal intensities from primary, scatter, and
      glare were quantified in images acquired with an a-Si/CsI(T1) FFDM detector using
      a Rh target and a 0.27 mm Cu filter at tube voltages ranging from 35 to 49 kV.
      Measurements were obtained at the center of the irradiation region of 20-80 mm
      thick breast-equivalent phantoms. The phantoms were imaged with and without an
      antiscatter grid. Based on these data, the performance of the antiscatter grid
      was determined by calculating the primary and scatter transmission factors (T(P)
      and T(S)) and Bucky factors (Bf). In addition, glare-to-primary ratios (GPRs) and
      scatter-to-primary ratios (SPRs) were quantified. The effect of the antiscatter
      grid on the signal-difference-to-noise ratio (SDNR) was also assessed. It was
      found that T(P) increases with kV but does not depend on the phantom thickness;
      T(P) values between 0.81 and 0.84 were measured. T(S) increases with kV and
      phantom thickness; T(S) values between 0.13 and 0.21 were measured. Bf decreases
      with kV and increases with phantom thickness; Bf ranges from 1.4 to 2.1. GPR is
      nearly constant, varying from 0.10 to 0.11. SPR without an antiscatter grid (SPR
      ) ranges from 0.35 to 1.34. SPR- decreases by approximately 9% from 35 to 49 kV
      for a given phantom thickness and is 3.5 times larger for an 80 mm thick breast
      equivalent phantom than for a 20 mm thick breast-equivalent phantom. SPR with an
      antiscatter grid (SPR+) ranges from 0.06 to 0.31. SPR+ increases by approximately
      23% from 35 to 49 kV for a given phantom thickness; SPR+ is four times larger for
      an 80 mm breast-equivalent phantom than for a 20 mm breast-equivalent phantom.
      When imaging a 25 mm PMMA plate at the same mean glandular dose with and without
      an antiscatter grid, the SDNR is 4% greater with a grid than without. For an 75
      mm PMMA plate, the SDNR is 20% greater with a grid. In conclusion, at the higher
      x-ray energy range used for CE-DM and CE-DBT, an antiscatter grid significantly
      reduces SPR and improves SDNR. These effects are most pronounced for thick
      breasts.

PMID- 19378753
TI  - Clinic based transfer of the N(D,W)(60Co) calibration coefficient using a linear
      accelerator.
AB  - Ionization chambers used for reference dosimetry require a local secondary
      standard ionization chamber with a 60Co absorbed dose to water calibration
      coefficient N(D,W)(60Co) traceable to a national primary standards dosimetry
      laboratory or an accredited secondary dosimetry calibration laboratory. Clinic
      based (in-house) transfer of this coefficient to tertiary reference ionization
      chambers has traditionally been accomplished with chamber cross calibration in
      water using a 60Co beam; however, access to 60Co teletherapy machines has become
      increasingly limited for clinic based physicists. In this work, the accuracy of
      alternative methods of transferring the N(D,W)(60Co) calibration coefficient
      using 6 and 18 MV photon beams from a linear accelerator in lieu of 60Co has been
      investigated for five different setups and four commonly used chamber types.

PMID- 19378754
TI  - Sensitivity of molecular target detection by multispectral optoacoustic
      tomography (MSOT).
AB  - Optoacoustic imaging is emerging as a noninvasive imaging modality that can
      resolve optical contrast through several millimeters to centimeters of tissue
      with the resolution achieved by ultrasound imaging. More recently, applied at
      multiple illumination wavelengths, multispectral optoacoustic tomography (MSOT)
      offered the ability to effectively visualize tissue biomarkers by resolving their
      distinct spectral signatures. While the imaging potential of the method has been
      demonstrated, little is known on the sensitivity performance in resolving
      chromophoric and fluorescent substances, such as optical functional and molecular
      reporters. Herein the authors investigate the detection capacity and physical
      limits of tomographic optoacoustic imaging by simulating signals originating from
      absorbing spheres in tissue-mimicking media. To achieve this, a modified
      optoacoustic equation is employed to incorporate wavelength-dependent propagation
      and attenuation of diffuse light and ultrasound. The theoretical predictions are
      further validated in phantom experiments involving Cy5.5, a common near-infrared
      fluorescent molecular agent.

PMID- 19378755
TI  - Portal dose image prediction for in vivo treatment verification completely based
      on EPID measurements.
AB  - A high dosimetric accuracy is required for radiotherapy treatments where IMRT in
      combination with narrow treatment margins is applied to achieve optimally
      conformal dose distributions. In order to routinely verify the in vivo fluence
      delivery (i.e., during the actual patient treatment), our method for predicting
      portal dose images with a patient in the beam was validated. A unique feature of
      this method is that it is fully based on calibration measurements with an EPID.
      The portal dose image (PDI) behind a patient is dependent on the transmission of
      primary radiation through the patient and a contribution of scattered radiation
      from the patient. To derive both components, the patient geometry as observed in
      the planning CT scan is converted into an equivalent homogeneous phantom. A
      limited set of EPID measurements is required to derive the input parameters of
      this model. The accuracy of the in vivo PDI prediction was verified using
      measurements behind phantoms and four prostate cancer patients treated with IMRT.
      Behind homogeneous slab phantoms, the local differences between measured and
      predicted PDIs were within 2% inside the field, while behind a lung and a pelvic
      phantom, the agreement was within 3% or within 3 mm in regions with steep
      gradients. Outside the fields, the PDIs agreed within 2% of the global dose
      maximum. Evaluation of the in vivo PDI measurements behind patients showed that,
      on average, 87% of the pixels inside the field fulfilled the 3% local dose and 3
      mm distance-to-agreement criteria. For half of the failing pixels the differences
      occurred due to changes in patient geometry with respect to the planning CT or
      due to beam attenuation by the treatment couch that was not accounted for. A
      fully EPID-based method for predicting portal dose images using the planning CT
      scan has been implemented and validated for phantoms and clinical patients.

PMID- 19378756
TI  - Air kerma standard for calibration of well-type chambers in Brazil using 192Ir
      HDR sources and its traceability.
AB  - In Brazil there are over 100 high dose rate (HDR) brachytherapy facilities using
      well-type chambers for the determination of the air kerma rate of 192Ir sources.
      This paper presents the methodology developed and extensively tested by the
      Laboratorio de Ciencias Radiologicas (LCR) and presently in use to calibrate
      those types of chambers. The system was initially used to calibrate six well-type
      chambers of brachytherapy services, and the maximum deviation of only 1.0% was
      observed between the calibration coefficients obtained and the ones in the
      calibration certificate provided by the UWADCL. In addition to its traceability
      to the Brazilian National Standards, the whole system was taken to the University
      of Wisconsin Accredited Dosimetry Calibration Laboratory (UWADCL) for a direct
      comparison and the same formalism to calculate the air kerma was used. The
      comparison results between the two laboratories show an agreement of 0.9% for the
      calibration coefficients. Three Brazilian well-type chambers were calibrated at
      the UWADCL, and by LCR, in Brazil, using the developed system and a clinical HDR
      machine. The results of the calibration of three well chambers have shown an
      agreement better than 1.0%. Uncertainty analyses involving the measurements made
      both at the UWADCL and LCR laboratories are discussed.

PMID- 19378757
TI  - Coverage-based treatment planning: optimizing the IMRT PTV to meet a CTV coverage
      criterion.
AB  - This work demonstrates an iterative approach-referred to as coverage-based
      treatment planning-designed to produce treatment plans that ensure target
      coverage for a specified percentage of setup errors. In this approach the
      clinical target volume to planning target volume (CTV-to-PTV) margin is
      iteratively adjusted until the specified CTV coverage is achieved. The advantage
      of this approach is that it automatically compensates for the dosimetric margin
      around the CTV, i.e., the extra margin that is created when the dose distribution
      extends beyond the PTV. When applied to 27 prostate plans, this approach reduced
      the average CTV-to-PTV margin from 5 to 2.8 mm. This reduction in PTV size
      produced a corresponding decrease in the volume of normal tissue receiving high
      dose. The total volume of tissue receiving > or =65 Gy was reduced on average by
      19.3% or about 48 cc. Individual reductions varied from 8.7% to 28.6%. The volume
      of bladder receiving > or =60 Gy was reduced on average by 5.6% (reductions for
      individuals varied from 1.7% to 10.6%), and the volume of periprostatic rectum
      receiving > or =65 Gy was reduced on average by 4.9% (reductions for individuals
      varied from 0.9% to 12.3%). The iterative method proposed here represents a step
      toward a probabilistic treatment planning algorithm which can generate dose
      distributions (i.e., treated volumes) that closely approximate a specified level
      of coverage in the presence of geometric uncertainties. The general principles of
      coverage-based treatment planning are applicable to arbitrary treatment sites and
      delivery techniques. Importantly, observed deviations between coverage implied by
      specified CTV-to-PTV margins and coverage achieved by a given treatment plan
      imply a generic need to perform coverage probability analysis on a per-plan basis
      to ensure that the desired level of coverage is achieved.

PMID- 19378758
TI  - Diagnostic detection of diffuse glioma tumors in vive with molecular fluorescent
      probe-based transmission spectroscopy.
AB  - The diffuse spread of glioma tumors leads to the inability to image and properly
      treat this disease. The optical spectral signature of targeted fluorescent probes
      provides molecular signals from the diffuse morphologies of glioma tumors, which
      can be a more effective diagnostic probe than standard morphology-based magnetic
      resonance imaging (MRI) sequences. Three orthotopic xenograft glioma models were
      used to examine the potential for transmitted optical fluorescence signal
      detection in vivo, using endogenously produced protoporphyrin IX (PpIX) and
      exogenously administered fluorescently labeled epidermal growth factor (EGF).
      Accurate quantification of the fluorescent signals required spectral filtering
      and signal normalization, and when optimized, it was possible to improve
      detection of sparse diffuse glioma tumor morphologies. The signal of endogenously
      produced PpIX provided similar sensitivity and specificity to MRI, while
      detection with fluorescently labeled EGF provided maximal specificity for tumors
      with high EGF receptor activity. Optical transmitted fluorescent signal may add
      significant benefit for clinical cases of diffuse infiltrative growth pattern
      glioma tumors given sufficient optimization of the signal acquisition for each
      patient.

PMID- 19378759
TI  - A simple approach to using an amorphous silicon EPID to verify IMRT planar dose
      maps.
AB  - A simplified method of verifying intensity modulated radiation therapy (IMRT)
      fields using a Varian aS500 amorphous silicon electronic portal imaging device
      (EPID) is demonstrated. Unlike previous approaches, it does not involve time
      consuming or complicated analytical processing of the data. The central axis
      pixel response of the EPID, as well as the profile characteristics obtained from
      images acquired with a 6 MV photon beam, was examined as a function of field
      size. Ion chamber measurements at various depths in a water phantom were then
      collected and it was found that at a specific depth d(ref), the dose response and
      profile characteristics closely matched the results of the EPID analysis. The
      only manipulation required to be performed on the EPID images was the
      multiplication of a matrix of off axis ratio values to remove the effect of the
      flood field calibration. Similarly, d(ref) was found for 18 MV. Planar dose maps
      at d(ref) in a water phantom for a bar pattern, a strip pattern, and 14 clinical
      IMRT fields from two patient cases each being from a separate anatomical region,
      i.e., head and neck as well as the pelvis, for both energies were generated by
      the Pinnacle planning system (V7.4). EPID images of these fields were acquired
      and converted to planar dose maps and compared directly with the Pinnacle planar
      dose maps. Radiographic film dosimetry and a MapCHECK dosimetry device (Sun
      Nuclear Corporation, Melbourne, FL) were used as an independent verification of
      the dose distribution. Gamma analysis of the EPID, film, and Pinnacle planar dose
      maps generated for the clinical IMRT fields showed that approximately 97% of all
      points passed using a 3% dose/3 mm DTA tolerance test. Based on the range of
      fields studied, the author's results appear to justify using this approach as a
      method to verify dose distributions calculated on a treatment planning system,
      including complex intensity modulated fields.

PMID- 19378760
TI  - Application- and patient size-dependent optimization of x-ray spectra for CT.
AB  - Although x-ray computed tomography (CT) has been in clinical use for over 3
      decades, spectral optimization has not been a topic of great concern; high
      voltages around 120 kV have been in use since the beginning of CT. It is the
      purpose of this study to analyze, in a rigorous manner, the energies at which the
      patient dose necessary to provide a given contrast-to-noise ratio (CNR) for
      various diagnostic tasks can be minimized. The authors used cylindrical water
      phantoms and quasianthropomorphic phantoms of the thorax and the abdomen with
      inserts of 13 mm diameter mimicking soft tissue, bone, and iodine for simulations
      and measurements. To provide clearly defined contrasts, these inserts were made
      of solid water with a 1% difference in density (DD) to represent an energy
      independent soft-tissue contrast of 10 Hounsfield units (HU), calcium
      hydroxyapatite (Ca) representing bone, and iodine (I) representing the typical
      contrast medium. To evaluate CT of the thorax, an adult thorax phantom (300 x 200
      mm2) plus extension rings up to a size of 460 x 300 mm2 to mimic different
      patient cross sections were used. For CT of the abdomen, we used a phantom of 360
      x 200 mm2 and an extension ring of 460 x 300 mm2. The CT scanner that the authors
      used was a SOMATOM Definition (Siemens Healthcare, Forchheim, Germany) at 80,
      100, 120, and 140 kV. Further voltage settings of 60, 75, 90, and 105 kV were
      available in an experimental mode. The authors determined contrast for the
      density difference, calcium, and iodine, and noise and 3D dose distributions for
      the available voltages by measurements. Additional voltage values and
      monoenergetic sources were evaluated by simulations. The dose-weighted contrast
      to-noise ratio (CNRD) was used as the parameter for optimization. Simulations and
      measurements were in good agreement with respect to absolute values and trends
      regarding the dependence on energy for the parameters investigated. For soft
      tissue imaging, the standard settings of 120-140 kV were found as adequate
      choices with optimal values increasing for larger cross sections, e.g., for large
      abdomens voltages higher than 140 kV may be indicated. For bone and iodine
      imaging the optimum values were generally found at significantly lower voltages
      of typically below 80 kV. This offers a potential for dose reduction of up to
      50%, but demands significantly higher power values in most cases. The authors
      concluded that voltage settings in CT should be varied more often than is common
      in practice today and should be chosen not only according to patient size but
      also according to the substance imaged in order to minimize dose while not
      compromising image quality. A reduction from 120 to 80 kV, for example, would
      yield a reduction in patient dose by more than half for coronary CT angiography.
      The use of lower voltages has to be recommended for contrast medium studies in
      cardiac and pediatric CT.

PMID- 19378761
TI  - A bone composition model for Monte Carlo x-ray transport simulations.
AB  - In the megavoltage energy range although the mass attenuation coefficients of
      different bones do not vary by more than 10%, it has been estimated that a simple
      tissue model containing a single-bone composition could cause errors of up to 10%
      in the calculated dose distribution. In the kilovoltage energy range, the
      variation in mass attenuation coefficients of the bones is several times greater,
      and the expected error from applying this type of model could be as high as
      several hundred percent. Based on the observation that the calcium and phosphorus
      compositions of bones are strongly correlated with the bone density, the authors
      propose an analytical formulation of bone composition for Monte Carlo
      computations. Elemental compositions and densities of homogeneous adult human
      bones from the literature were used as references, from which the calcium and
      phosphorus compositions were fitted as polynomial functions of bone density and
      assigned to model bones together with the averaged compositions of other
      elements. To test this model using the Monte Carlo package DOSXYZnrc, a series of
      discrete model bones was generated from this formula and the radiation-tissue
      interaction cross-section data were calculated. The total energy released per
      unit mass of primary photons (terma) and Monte Carlo calculations performed using
      this model and the single-bone model were compared, which demonstrated that at
      kilovoltage energies the discrepancy could be more than 100% in bony dose and 30%
      in soft tissue dose. Percentage terma computed with the model agrees with that
      calculated on the published compositions to within 2.2% for kV spectra and 1.5%
      for MV spectra studied. This new bone model for Monte Carlo dose calculation may
      be of particular importance for dosimetry of kilovoltage radiation beams as well
      as for dosimetry of pediatric or animal subjects whose bone composition may
      differ substantially from that of adult human bones.

PMID- 19378762
TI  - Image quality optimization and evaluation of linearly mixed images in dual
      source, dual-energy CT.
AB  - In dual-source dual-energy CT, the images reconstructed from the low- and high
      energy scans (typically at 80 and 140 kV, respectively) can be mixed together to
      provide a single set of nonmaterial-specific images for the purpose of routine
      diagnostic interpretation. Different from the material-specific information that
      may be obtained from the dual-energy scan data, the mixed images are created with
      the purpose of providing the interpreting physician a single set of images that
      have an appearance similar to that in single-energy images acquired at the same
      total radiation dose. In this work, the authors used a phantom study to evaluate
      the image quality of linearly mixed images in comparison to single-energy CT
      images, assuming the same total radiation dose and taking into account the effect
      of patient size and the dose partitioning between the low-and high-energy scans.
      The authors first developed a method to optimize the quality of the linearly
      mixed images such that the single-energy image quality was compared to the best
      case image quality of the dual-energy mixed images. Compared to 80 kV single
      energy images for the same radiation dose, the iodine CNR in dual-energy mixed
      images was worse for smaller phantom sizes. However, similar noise and similar or
      improved iodine CNR relative to 120 kV images could be achieved for dual-energy
      mixed images using the same total radiation dose over a wide range of patient
      sizes (up to 45 cm lateral thorax dimension). Thus, for adult CT practices, which
      primarily use 120 kV scanning, the use of dual-energy CT for the purpose of
      material-specific imaging can also produce a set of non-material-specific images
      for routine diagnostic interpretation that are of similar or improved quality
      relative to single-energy 120 kV scans.

PMID- 19378763
TI  - Variability of surface and center position radiation dose in MDCT: Monte Carlo
      simulations using CTDI and anthropomorphic phantoms.
AB  - The larger coverage afforded by wider z-axis beams in multidetector CT (MDCT)
      creates larger cone angles and greater beam divergence, which results in
      substantial surface dose variation for helical and contiguous axial scans. This
      study evaluates the variation of absorbed radiation dose in both cylindrical and
      anthropomorphic phantoms when performing helical or contiguous axial scans. The
      approach used here was to perform Monte Carlo simulations of a 64 slice MDCT.
      Simulations were performed with different radiation profiles (simulated beam
      widths) for a given collimation setting (nominal beam width) and for different
      pitch values and tube start angles. The magnitude of variation at the surface was
      evaluated under four different conditions: (a) a homogeneous CTDI phantom with
      different combinations of pitch and simulated beam widths, (b) a heterogeneous
      anthropomorphic phantom with one measured beam collimation and various pitch
      values, (c) a homogeneous CTDI phantom with fixed beam collimation and pitch, but
      with different tube start angles, and (d) pitch values that should minimize
      variations of surface dose-evaluated for both homogeneous and heterogeneous
      phantoms. For the CTDI phantom simulations, peripheral dose patterns showed
      variation with percent ripple as high as 65% when pitch is 1.5 and simulated beam
      width is equal to the nominal collimation. For the anterior surface dose on an
      anthropomorphic phantom, the percent ripple was as high as 40% when the pitch is
      1.5 and simulated beam width is equal to the measured beam width. Low pitch
      values were shown to cause beam overlaps which created new peaks. Different x-ray
      tube start angles create shifts of the peripheral dose profiles. The start angle
      simulations showed that for a given table position, the surface dose could vary
      dramatically with minimum values that were 40% of the peak when all conditions
      are held constant except for the start angle. The last group of simulations
      showed that an "ideal" pitch value can be determined which reduces surface dose
      variations, but this pitch value must take into account the measured beam width.
      These results reveal the complexity of estimating surface dose and demonstrate a
      range of dose variability at surface positions for both homogeneous cylindrical
      and heterogeneous anthropomorphic phantoms. These findings have potential
      implications for small-sized dosimeter measurements in phantoms, such as with
      TLDs or small Farmer chambers.

PMID- 19378764
TI  - Comment on "Monte Carlo simulation of an x-ray volume imaging cone beam CT unit"
      [Med. Phys. 36, 127-136 (2009)].

PMID- 19378766
TI  - [Study on the blood concentration and clinical efficacy of ceftazidime, a cephem
      antibiotic at dose of one gram q.i.d, for adult hospital-acquired pneumonia
      patients].
AB  - Ceftazidime (CAZ), a cephem antibiotic for injection, was administered at dose of
      one gram q.i.d. to adult hospital-acquired pneimonia patients, and the clinical
      efficacy and blood concentration of CAZ was studied in five cases. The assessment
      of clinical efficacy was "efficacy" in all cases, and early improvement of
      examination value including body temperature, the value of CRP, and white blood
      cell counts were obtained. Abnormality of hepatic function as adverse effect was
      noted in two cases. However, the severity was mild and didn't affect the
      treatment in both cases. The maximum drug concentration immediately after the end
      of infusion was 72.1-176.5 microg/mL (median, 82.7 microg/mL) and the trough
      level was 5.1-72.1 microg/mL (median, 26.6 microg/mL), therefore the blood
      concentration was maintained a higher level than the MIC of bacteria estimated to
      be causative. From these results, administration method of ceftazidime one gram
      q.i.d. was considered to be a good way with increase of drug efficacy by
      maintaining highly blood concentration over prolonged period, and expected to be
      a good effect for hospital-acquired pneumonia.

PMID- 19378765
TI  - [Dosing regimen rationalization of biapenem in pediatric patients: use of Monte
      Carlo simulation].
AB  - Biapenem has been used in pediatric patients as well as adult patients; however,
      little information is available on dosing regimens for pediatric patients. This
      study examined biapenem pharmacokinetics in pediatric population and performed
      pharmacokinetic-pharmacodynamic analysis. Biapenem plasma concentrations from 10
      pediatric patients were pharmacokinetically analyzed. A multi-regression analysis
      showed the pharmacokinetic parameters were affected by body weight and creatinine
      clearance of the patients. Using the pharmacokinetic parameters, a Monte Carlo
      simulation predicted the probabilities of attaining the pharmacodynamic target
      (40% of the time above the minimum inhibitory concentration for the bacterium).
      In the case of about 20 kg, biapenem regimens of 5 mg/kg b.i.d. and 10 mg/kg
      b.i.d. provided sufficient target attainment probabilities against Streptococcus
      pneumoniae and Pseudomonas aeruginosa isolates, respectively. Our results should
      provide a PK-PD-based guidance for rationalizing biapenem regimen according to
      the body weight and renal function of a pediatric patient and the specific
      bacterium suspected.

PMID- 19378767
TI  - [Development of treatment adherence by jellification of itraconazole oral
      solution].
AB  - There have been some reports on the efficacy and tolerability of itraconazole
      (ITCZ) as prophylaxis for fungal infection after HSCT, and guidelines recommend
      itraconazole as a standard drug for prophylaxis of fungal infection in HSCT
      patients. However, it is not uncommon for patients undergoing HSCT to develop
      anorexia and taste disturbance. There are some cases where the bitter taste of
      ITCZ oral solution leads to interruption of administration because the patient
      refuses to take this medicine. Therefore, we investigated the clinical utility
      and influence on continuing treatment adherence by jellification of ITCZ.
      Compared with ITCZ oral solution, jellified ITCZ was extremely easy for most
      patients to take, and it was suggested that jellified ITCZ can make it easier for
      patients to continue treatment if they have difficulty with administration
      because of the bitter taste of ITCZ oral solution. Furthermore, it was confirmed
      that the plasma concentration of ITCZ was suitable for prophylaxis even with
      jellified ITCZ. This also suggested that the efficacy of ITCZ would be maintained
      by using jellified formation. For long-term antifungal therapy in patients with a
      high risk of fungal infection such as those having HSCT, it is very important for
      successful prophylaxis to maintain good adherence.

PMID- 19378768
TI  - [The 1st Kantou Symposium on Respiratory Mycosis: Autopsy case of invasive
      mucormycoses manifested as breakthrough infection].

PMID- 19378769
TI  - [Paroxysmal perceptual alteration in comparison with hallucination--a review of
      its clinical reports and discussion of its pathophysiological mechanism in the
      present day, when second generation antipsychotics are widely used].
AB  - The syndrome of paroxysmal perceptual alteration (PPA) was first described by
      Yamaguchi in 1985. Since then, many PPA cases have been reported, and its
      pathophysiological mechanism has been proposed: a suppressed (blocked) mesolimbic
      and mesocortical dopaminergic system and sequential compensatory increase of
      noradrenergic neuronal activity are crucial for the occurrence of PPA. PPA is
      characterized by hypersensitivity of perception, psychedelic experience
      (brightening of colors, sharpening of contrast, visual distortion, etc.), and
      somatic schema disorder (one feels that one is floating, one's extremities are
      being pulled and elongated, etc.). PPA in chronic schizophrenic patients occurs
      abruptly like an attack mainly in the evening, often precipitated by fatigue.
      During the attack, patients also suffer from mood and thought alteration
      (anxiety, agitation, depressive mood, and inability to distract their thoughts
      from one thing), but they are aware that symptoms of PPA are not real and
      apprehensive about them. The attack ceases gradually and spontaneously while the
      patient rests or sleeps. These clinical features are clearly different from those
      of schizophrenic hallucinations. It is believed that PPA is closely related to
      neuroleptic treatment by conventional antipsychotics. I reported the prevalence
      of PPA as 4.0% in 1991 when high potential D2 blocking agents were prevailing.
      The occurrence of PPA has been significantly reduced to the present, when second
      generation (atypical) antipsychotics are prevailing. However, in my inquiry in
      2004, the prevalence of PPA was 3.6% in cases treated with risperidone (RIS),
      while the rates were 0 in cases treated with olanzapine (OLZ), quetiapine (QTP),
      and perospirone (PRS). Several cases of PPA have been reported in patients who
      were treated with OLZ and PRS. Until now, no cases of PPA have been reported who
      were treated with QTP and aripiprazole (APZ). The prevalence of PPA among cases
      treated with these second generation antipsychotics might be related to the
      differences in these agents regarding their affinity for the D2 receptor: RIS has
      a sustained and close binding affinity, which might be similar to those of
      conventional antipsychotics, OLZ shows a sustained and loose binding affinity,
      PRS exhibits a transient and close binding affinity, whereas QTP has a transient
      and loose binding affinity. APZ is a partial agonist of the D2 receptor; APZ acts
      as an agonist under the condition of intrinsic dopaminergic dysfunction, which
      might prevent the occurrence of PPA.

PMID- 19378770
TI  - [Two adolescent cases of pseudoseizure with mental retardation].
AB  - We experienced two cases of complicated pseudoseizure, whose diagnosis and
      treatment were based on Kretschmer's concept of "primitive hysteria". The first
      case was a 16-year-old boy who experienced a convulsion before a swimming class
      which he disliked. He was immediately brought to the emergency department of our
      hospital. Initially, he was treated as a true epileptic patient, and his
      convulsion continued for hours. We monitored the patient by video, which aided in
      making a precise diagnosis. He also showed a pain disorder. The second case was a
      16-year-old girl who developed hyperventilation and convulsion during her
      graduation ceremony. The characteristics of her convulsion were similar to the
      first case. Four days after her admission to our hospital, we concluded that her
      symptoms were a part of primitive hysteria. After her discharge, she experienced
      some intermittent episodes of convulsion. There was also a possibility of sexual
      abuse from her father. Both patients had a family history of mental retardation
      and an unstable home life, as well as similar symptoms. Even in a modern general
      hospital, there is a lack of understanding about pseudoseizure, thus, medication
      may be unnecessary for undiagnosed patients. DSM-IV-TR as well as ICD-10 criteria
      do not mention anything about primitive hysteria. However, we recommend
      revitalization of this concept because it is a useful, appropriate, and necessary
      description of pseudoseizure with complications.

PMID- 19378771
TI  - [Recent topics in development and progression of atherosclerosis].

PMID- 19378772
TI  - [Histopathology and molecular biological behaviors in human malignant neoplasms].

PMID- 19378773
TI  - Retrospective analysis: concurrent chemoradiotherapy and adjuvant chemotherapy
      for T2N0 glottic squamous cell carcinoma.
AB  - This study aimed to evaluate the efficacy and toxicity of concurrent
      chemoradiotherapy and adjuvant chemotherapy for T2N0 glottic squamous cell
      carcinoma. Between May 1993 and March 2004, 32 patients with T2N0 glottic
      squamous cell carcinoma received concurrent chemoradiotherapy as the primary
      treatment modality for larynx preservation. Radiotherapy was delivered five days
      a week using a once-daily fractionation of 2.0 Gy (median total dose: 70 Gy). The
      chemotherapy regimen comprised carboplatin in 4 patients, carboplatin and tegafur
      and uracil in 7, carboplatin and futraful in 2, and futraful in 19 patients.
      Twenty-four patients received adjuvant chemotherapy with tegafur and uracil.
      Initial local tumor control was achieved in 30 patients (94%). The 5-year overall
      survival and 5-year local control rates were 97% and 70%, respectively.
      Univariate analysis revealed adjuvant chemotherapy as a significant prognostic
      factor for the local control rate (P = 0.038). The 5-year local control rate in
      patients treated or not treated with adjuvant chemotherapy was 82% and 42%,
      respectively. No significant differences in the local control rate were noted in
      overall treatment time, total radiation dose, age, and disease extension to the
      subglottis. With regard to adverse reactions, grade 3 neutropenia and grade 3
      hepatotoxicity were observed in 1 and 2 patients, respectively. We observed no
      severe late complications (RTOG/EORTC criteria Grade 3-4) related to this
      combination therapy. Concurrent chemoradiotherapy and adjuvant chemotherapy was
      effective but with mild toxicity, and adjuvant chemotherapy significantly
      improved local control. We suggest the use of this combination therapy for
      achieving a local control of T2N0 glottic squamous cell carcinoma.

PMID- 19378774
TI  - [Research of transcutaneous and transmucosal drug delivery and its perspective].

PMID- 19378775
TI  - [Radiotherapy for oral tumors and translational research].

PMID- 19378776
TI  - [Changing trend over time of psychological states and quality of life of oral
      cancer patients with surgery].
AB  - This study examines the psychological states and QOL in oral cancer patients
      during the perioperative and postoperative survival periods. Those patients who
      were scheduled for and had undergone primary surgery at the Oral and
      Maxillofacial Surgery Section, Tokyo Medical and Dental University Hospital,
      Tokyo, Japan were selected for this study. They took two different kinds of
      tests, i. e. the Hospital Anxiety and Depression Scale (HADS) and the Japanese
      language version of the Functional Assessment of Cancer Therapy Head and Neck
      (FACT-H & N) version 4. In a longitudinal study, interval assessments were done
      at one day before surgery, one week after surgery and one month and six months
      each after being discharged from the hospital, respectively. In a cross-sectional
      study, outpatients during the postoperative follow-up periods were evaluated.
      Statistically, before surgery psychological anxiety became highest, while after
      surgery depression grew and QOL in the somatic and specific domains decreased.
      After discharge from the hospital, the patients with longer-term postoperative
      survival had better psychological states and QOL. These results provide important
      information regarding psychological states and QOL in oral cancer patients for
      caring and supporting based on perioperative and postoperative periods.

PMID- 19378777
TI  - [Effectiveness and difficulty of education on nosocomial infection control for
      pre-clinical practice in the clinic, so-called inclusive clinical practice phase
      I, for students in the Faculty of Dentistry, Tokyo Medical and Dental
      University].
AB  - It has been planned to give pre-clinical practice in the clinic, so-called
      inclusive clinical practice phase I, for fifth-grade students in the School of
      Dentistry, Faculty of Dentistry, Tokyo Medical and Dental University, to give
      them the clinical training needed to perform dental practice and clinical
      practicum for comprehensive patient care, namely inclusive clinical practice
      phase II. This study analyzed the educative efficiency of the class on nosocomial
      infection control (NIC) by comparing achievements pre- and post-test, and
      discussed appropriate education planning on the NIC for dental students. Sixty
      two fifth-grade students in the 2007 academic year sat the pre- and post-tests;
      the mean score and standard deviation of these tests were 5.30 +/- 1.26 (n = 56)
      and 8.59 +/- 1.18 (n = 59), respectively. There was a statistically significant
      difference between them (paired t-test, p < 0.01). Another finding was that
      students with high scores in the post-test did not necessarily achieve high
      ratings in the pre-test. It is suggested that the introduction of pre- and post
      tests and the clarification of main points in the class as a theme of NIC could
      be a useful tool for increasing the comprehension of students on the theme. Since
      students at lower grades will attend clinical practice in the university
      hospital, it is thought that students should be given NIC training early in the
      clinical course, and the current curriculum should be improved to increase the
      opportunity for students to study this important issue.

PMID- 19378778
TI  - [Fluorescence analysis of oral squamous cell carcinoma with 5-aminolevulinic acid
      labeling].
AB  - Photodynamic diagnosis (PDD) is a form of cancer detection based on the
      administration of an exogenous photoactivated compound that accumulates in
      malignant cells, followed by appropriate photo-irradiation. 5-aminolevulinic acid
      (5-ALA), which is one of these compounds, is a prodrug of the photosensitizer
      protoporphyrin IX (PpIX). This report describes a spectroscopic study of 5-ALA
      generated PpIX fluorescence in human oral cancer cell lines. After transplanting
      five human oral squamous carcinoma cell lines into scid mice, the degree of tumor
      differentiation was evaluated by hematoxylin-and-eosin staining. Two, one, and
      two cell lines were poorly, moderately, and well differentiated, respectively.
      Under cell culture conditions, well and moderately differentiated cancer cells
      showed higher positive staining rates of AE1/AE3 than poorly differentiated ones
      in immunohistochemistry. 5-ALA-induced PpIX fluorescence intensities of five cell
      lines, which were cultured in Dulbecco's Modified Eagle's Medium (DMEM) treated
      with or without deferoxamine mesylate (DFO), were measured. In all cell lines,
      the maximum 5-ALA-generated fluorescence intensity was found in the presence of
      DFO. The fluorescence intensity varied with the degree of tumor differentiation
      in the following order: poorly differentiated, moderately differentiated, well
      differentiated. These results suggest that the fluorescence intensity of oral
      cancer cells differs according to the degree of tumor differentiation. However,
      even with well differentiated cancer cells, addition of DFO could increase the
      photodynamic sensitivity of 5-ALA as a result of greater cellular accumulation of
      PpIX.

PMID- 19378779
TI  - [Observation of pulpal blood flow and bone mineralization after alveolar
      distraction osteogenesis in a canine cleft model].
AB  - OBJECTIVE: Distraction osteogenesis has been widely used for the craniofacial
      region and even applied to alveolar bones to reduce the cleft width of cleft lip
      and/or palate patients. However, there have been no reports on the limitations on
      the total amount of lengthening that can be accomplished by distraction
      osteogenesis in this area. Therefore, we investigated how different extents of
      distraction osteogenesis affect the healing process using a canine cleft palate
      model. METHODS: Six beagle dogs were used in this study. A bony segment including
      the canine was prepared and translocated into a 10-mm bone defect area, imitating
      a cleft, at a rate of 1 mm/day for six or ten days, resulting in two groups (6-
      and 10-mm groups). Canine pulpal blood flow was monitored for 100 days by Doppler
      flowmetry. The animals were then sacrificed and the regenerated bone area was
      evaluated using peripheral quantitative computed tomography (pQCT) and a
      histological process. Statistical significance was confirmed by the Mann-Whitney
      rank sum test. RESULTS: Pulpal blood flow recovered to the original levels
      significantly earlier in the 6-mm group. It was shown by pQCT evaluation that
      cortical bone density in the regenerated bone was significantly higher in the 6
      mm group. The amount of regenerated bone in histological sections was also
      significantly higher in the 6-mm group than in the 10-mm group. CONCLUSION: We
      revealed that the amount of bone lengthening affects the progress of healing.
      These results suggest the importance of limited distraction osteogenesis in the
      maxillofacial area.

PMID- 19378781
TI  - [Generation of T-lineage cells and their functions].

PMID- 19378780
TI  - [Molecular basis of immune defense mechanism].

PMID- 19378782
TI  - [Role of Toll-like receptors in innate and adaptive immune responses].

PMID- 19378783
TI  - [Nucleic acid sensors in innate immunity].

PMID- 19378784
TI  - [Innate immune functions of pulmonary collectins].

PMID- 19378785
TI  - [Structure and function of non-classical MHC class I molecules].

PMID- 19378786
TI  - [Novel mechanism of herpes simplex virus type-I infection].

PMID- 19378787
TI  - [Perspective of prevention and treatment for allergic diseases].

PMID- 19378788
TI  - [Single molecule imaging of molecular dynamics in immune cells].

PMID- 19378789
TI  - [Regulation of immune response by ubiquitin-like molecule ISG15].

PMID- 19378790
TI  - [Present status and future perspective of RPGN in Japan].

PMID- 19378791
TI  - [Epidemiology of rapidly progressive glomerulonephritis (RPGN) and ANCA
      associated vasculitis].

PMID- 19378792
TI  - [ANCA associated vasculitis and PRGN].

PMID- 19378793
TI  - [Anti-GBM glomerulonephritis and RPGN].

PMID- 19378794
TI  - [Immune complex glomerulonephritis and rapidly progressive glomerulonephritis].

PMID- 19378795
TI  - [RPGN in children].

PMID- 19378796
TI  - [Treatment of rapidly progressive glomerulonephritis].

PMID- 19378797
TI  - [Strategy of immunosuppressants usage for subjects with loss of renal function
      and infection control on RPGN].

PMID- 19378798
TI  - [Effect of oral adsorbent AST-120 under standard treatment of care in patients
      with chronic renal failure].
AB  - BACKGROUND: Oral adsorbent AST-120 reduces uremic toxins, such as indoxyl
      sulfate, and retards the progression of chronic kidney disease (CKD). The present
      study was conducted to elucidate the association between the progression of CKD
      and the combined effect of AST-120 and standard care based on diet therapy and
      medications such as ACE inhibitor and ARB. METHOD: Retrospective analysis was
      performed using forty-four CKD patients (chronic glomerular nephritis 16,
      diabetic nephropathy 9, nephrosclerosis 13, and others 6) who were treated by AST
      120 during the period from October, 2001 through December, 2004 and followed up
      for more than 6 months. The selection criteria were an estimated creatinine
      clearance (eCCr) of 30 mL/min or under at the initiation of treatment and a
      negative change in eCCr over time (DeltaeCCr (mL/min/year)) before AST-120
      treatment. The eCCr was calculated using the Cockcroft-Gault equation and the
      DeltaeCCr was evaluated as a marker for the progression of chronic renal failure.
      RESULT: Overall DeltaeCCr before and after AST-120 treatment significantly
      improved from -7.28 +/- 6.33 to -4.29 +/- 5.09 (paired Wilcoxon test, p < 0.05).
      AST-120 led to greater improvement of DeltaeCCr in patients with an DeltaeCCr of
      less than -10 mL/min/year before AST-120 treatment and who had higher blood uric
      acid, urinary protein, and urinary specific gravity valves. CONCLUSION: This
      finding suggests that AST-120 treatment is effective in slowing the progression
      of chronic kidney disease, especially, in patients who exhibit a poor response to
      standard care.

PMID- 19378799
TI  - [Minimal change nephrotic syndrome complicated with recurrence of malignant
      thymoma: an interesting case with remission due to steroid therapy of both
      nephrotic syndrome and thymoma].
AB  - A 65-year-old man was admitted to our hospital with abdominal fullness and leg
      edema in April 2005. Diabetes mellitus and hypertension that had been diagnosed
      in 1990 were well-controlled with oral hypoglucemic drug. He presented with
      malignant thymoma accompanied by multiple metastases in the right thoracic space
      in December 2000. He was treated with total thymectomy, combined with
      chemotherapy (cisplatin + vinorelbin) and hyperthermia. This strategy obviously
      reduced the tumor mass. However, CT scans showed multiple recurrences of thymoma
      in December 2004 and abdominal fullness and leg edema appeared shortly
      thereafter. Laboratory findings revealed proteinuria (over 10 g/day),
      hypoalbuminemia, hyperlipidemia and renal dysfunction. A kidney biopsy revealed
      minor glomerular abnormality. He was diagnosed with minimal change nephrotic
      syndrome (MCNS) complicated with the recurrence of malignant thymoma.
      Corticosteroid therapy was started, but dialysis was transiently required to
      protect against oliguric acute renal failure. Three weeks after the initiation of
      steroid therapy, the proteinuria was improved to less than 1.0 g/day and renal
      function returned to within the normal range. Subsequent corticosteroid combined
      with immunosuppressive therapy resulted in good control of his nephrotic syndrome
      (NS) without recurrence. There have been a few case reports showing NS
      complicated with malignant thymoma. Among these, several cases with MCNS occurred
      after thymectomy for malignant thymoma. Interestingly, both the thymoma mass and
      high pre-treatment vascular endothelial growth factor (VEGF) levels decreased as
      NS improved with steroid therapy. These findings suggest that VEGF also might
      have been associated with the onset of NS in this patient.

PMID- 19378800
TI  - [Nephrotic syndrome associated with lung adenocarcinoma: report of an autopsy
      case].
AB  - A 73-year-old male with nephrotic syndrome was admitted to our hospital. He was
      empirically treated with prednisolone, which resulted in the alleviation of
      proteinuria, hypoproteinemia, and pleural effusion. Thereafter, a computed
      tomographic scan revealed a mass lesion in the right-lower lung field. Finally,
      the patient died of multiple organ failure induced by disseminated intravascular
      coagulation. Adenocarcinoma of the lung and membranous nephropathy (MN) were
      revealed by autopsy. MN tends to occur in the elderly, and is also occasionally
      associated with solid tumors, such as lung and gastrointestinal cancer.
      Therefore, a malignancy survey may be useful in the management of cases with
      nephrotic syndrome in which MN is pathologically defined. However, the initiation
      of empirical treatment without a pathological diagnosis is not an exceptional
      phenomenon. Physicians should, therefore, bear in mind the potential association
      of malignancy and immediately and carefully investigate the potential presence of
      a malignancy in elderly patients with a new onset of nephrotic syndrome.

PMID- 19378801
TI  - [Case of Henoch-Schonlein purpura nephritis associated with IgA monoclonal
      gammopathy of undetermined significance].
AB  - We report the case of a 72-year-old man with nephritic syndrome and rapidly
      progressive renal failure due to Henoch-Schonlein purpura nephritis (HSPN). He
      was successfully treated with methylprednisolone pulse therapy, followed by oral
      prednisolone at the dose of 30 mg per day. He was also diagnosed by
      immunoelectrophoresis as IgA-lambda monoclonal gammopathy of undetermined
      significance (IgA-MGUS). Renal biopsy revealed the diffuse crescentic
      glomerulonephritis associated with mesangial deposition of IgA and C3. Since an
      immunofluorescence examination failed to show the deposition of lambda, the
      significance of IgA paraproteinemia on the HSPN was obscure in the present case.
      However, we must bear in mind the latent presence of IgA-MGUS in cases of HSPN.

PMID- 19378802
TI  - [Recent advances in research on basal ganglia. Introduction].
AB  - The basal ganglia consist of the striatum, globus pallidus, substantia nigra, and
      subthalamic nucleus. Further, the striatum is classified into the caudate nucleus
      and the putamen; the globus pallidus, into the external (GPe) and internal
      segments (GPi); and the substantia nigra, into the pars compacta (SNc) and pars
      reticulata (SNr). With regard to the framework of information flow, the striatum
      constitutes the input station of the basal ganglia, and both the GPi and SNr
      constitute the output stations. Dopaminergic input from the SNc modulates the
      activity of striatal neurons. In the basal ganglia, there is a direct pathway
      that links the input and output stations and an indirect pathway that connects
      these stations by way of the GPe and the subthalamic nucleus. These 2 pathways
      regulate the net activity of the basal ganglia, thus providing the processed
      information to output targets, such as the thalamus.

PMID- 19378803
TI  - [Anatomical connections of the basal ganglia].
AB  - The basal ganglia consist of the striatum, which includes the caudate-putamen and
      the core of the nucleus accumbens, the external segment of the globus pallidus
      (GPe), the subthalamic nucleus, the internal segment of the globus pallidus
      (GPi), and the substantia nigra (SN). The major input to the basal ganglia is
      glutamatergic striatopetal projections from nearly all areas of the neocortex and
      the intralaminar and midline nuclei. The striatofugal projection neurons are
      divided into 2 groups; one includes neurons projecting to the SN and GPi, and the
      other includes those projecting to the GPe. The former neurons are called 'direct
      pathway' neurons in the basal ganglia circuit, since they directly extend their
      axons to the output nuclei of the basal ganglia, i.e. pars reticulata of the SN
      (SNr) and GPi. On the other hand, the latter striato-GPe neurons are called
      'indirect pathway' neurons and contain striato-GPe, GPe-subthalamic, and
      subthalamo-GPi/SNr projections. The output of the basal ganglia is the projection
      of GABAergic neurons in the GPe and SNr. In addition to the 2 segregated
      striatofugal groups, the neostriatum possesses a mosaic organization composed of
      patch and matrix compartments. The patch compartment occupies 10-15% of the
      neostriatal volume and is characterized by its projection to the pars compacta of
      the SN (SNc). The basal ganglia output targets the thalamic nuclei, which are
      part of cortico-basal ganglia circuits, the intermediate layers of the superior
      colliculus, and the pedunculopontine nucleus. The basal ganglia possess not only
      the topographic organization that provides parallel and functionally defined
      loops but also the divergence and convergence connections, which may reflect the
      organizational features of the basal ganglia.

PMID- 19378804
TI  - [Cortico-basal ganglia circuits--parallel closed loops and convergent/divergent
      connections].
AB  - The basal ganglia play important roles not only in motor control but also in
      higher cognitive functions such as reinforcement learning and procedural memory.
      Anatomical studies on the neuronal connections between the basal ganglia,
      cerebral cortex, and thalamus have demonstrated that these nuclei and cortical
      areas are interconnected via independent parallel loop circuits. The association,
      motor, and limbic cortices project to specific domains in the striatum, which, in
      turn, project back to the corresponding cortical areas via the substantia
      nigra/globus pallidus and the thalamus. Likewise, subregions in the motor cortex
      representing different body parts project to specific regions in the putamen,
      which project back to the original motor cortical regions. These parallel loops
      have been thought to be the basic anatomical structures involved in the basal
      ganglia functions. Furthermore, neuronal projections communicating between
      different loops (or functional domains) have also been discovered. A considerable
      number of corticostriatal projections from functionally interrelated cortical
      areas (e. g., hand representations of the motor cortex and somatosensory cortex)
      converge at the striatum. It has also been suggested that the location of the
      substantia nigra is in such that it can transmit information from the 'limbic
      loop' to the 'association loop', and from the 'association loop' to the 'motor
      loop'. Furthermore, a recent transsynaptic neuronal tracing study conducted at
      our laboratory demonstrated that the ventral (limbic) striatum sends divergent
      outputs to multiple regions in the frontal cortex. These 'inter-loop' connections
      would be important for the integration of information to achieve goal-directed
      behaviors.

PMID- 19378805
TI  - [Functions of direct, indirect and hyperdirect pathways].
AB  - The 'direct and indirect pathways model' that was proposed almost 20 years ago
      revolutionarily changed our understanding of the basal ganglia and was successful
      in explaining certain aspects of the pathophysiology of movement disorders.
      However, many evidences and results that contradict this model have emerged
      during the last decade. In this article, I will introduce the 'cortico-subthalamo
      pallidal hyperdirect pathway' that has become a focus of attention recently and
      discuss the functions of the basal ganglia with the emphasis on the following
      four topics: first, effectiveness and limitations of the classical 'direct and
      indirect pathways model'; second, focused selection of movements and motor
      learning; third, firing rate model versus firing pattern model on the
      pathophysiology of movement disorders; and lastly, mechanisms of stereotaxic
      surgery.

PMID- 19378806
TI  - [Physiological interaction between acetylcholine and dopamine in the striatum].
AB  - The breakdown of the balance between acetylcholine and dopamine in the striatum
      is known to cause a variety of neurological diseases. Physiologically, the
      association between sensory cues and reward during behavioral learning gradually
      forms a conditional pause response in the firing of the tonically active
      cholinergic interneurons in the striatum. Simultaneous recordings of striatal
      cholinergic interneurons and midbrain dopaminergic neurons during the task
      revealed that the pause response was well synchronized with the increase in the
      firing frequency of the dopaminergic neurons. Recent studies have indicated that
      the content of released dopamine is proportional to the firing frequency of the
      dopaminergic neurons unless the nicotinic receptors are activated, but it remains
      unaltered if the receptors are bound by acetylcholine. Therefore, dopamine
      release would be dramatically increased during the pause response of the
      cholinergic neurons. The pause response is composed of an initial depolarization
      phase, a pause phase, and a rebound facilitation phase. Dopamine D5 receptor
      dependent long-term potentiation underlies the initial depolarization phase,
      which causes the ensuing pause phase. The termination of the pause is further
      delayed by suppression of Ih and sodium channels through dopamine D2 receptor
      activation. This facilitates the synaptic efficacy of the striatal medium spiny
      projection neurons, which enables the execution of action commands with an
      improved signal-to-noise ratio.

PMID- 19378807
TI  - [Glucose metabolism in the basal ganglia].
AB  - GABAergic neurons in the substantia nigra pars reticulata (SNr) -a major output
      nucleus of the basal ganglia- are involved in sensing severe hypoglycemic and
      hypoxic conditions in the brain via the ATP-sensitive potassium (KATP) channels
      that are abundantly expressed in these neurons. However, these neurons are also
      sensitive to mild changes in extracellular glucose concentrations through KATP
      channel-independent, yet unknown mechanisms. Lenard et al. reported that globus
      pallidus (GP) -another output nucleus of the basal ganglia- also senses glucose
      concentrations in the brain. It is unclear why these two major output nuclei
      sense glucose concentrations. It has been reported that some SNr and GP neurons
      respond to feeding-related, jaw or hand movement. Interestingly, Nishino
      demonstrated that SNr neurons responded oppositely, i.e., increased or decreased
      in their firings, to the same sweet food depending on blood glucose levels. Thus,
      glucose levels might influence feeding-related information processing in the
      basal ganglia through SNr and GP. Other issues reviewed are regarding
      associations between glucose metabolism and motor diseases in the basal ganglia.
      These include mutation in glucose transporter (GLUT) 1 causing paroxysmal
      kinesigenic choreoarthetosis, abnormal glycolysis in Huntington's disease, and a
      study showing increased glucose metabolism in SNr and GP in Parkinson's disease
      using high-resolution research positron emission tomography (HRRT). Although
      glucose is the sole energy source for the brain, its utilization at the single
      cell level remains elusive. Modern methods for investigating intercellular
      metabolic communication might help understanding the selective vulnerability seen
      in the basal ganglia of patients suffering from such neurodegenerative disorders
      in near future.

PMID- 19378808
TI  - [Role of the lateral habenula and dopamine neurons in reward processing].
AB  - Dopamine neurons in the substantia nigra pars compacta and ventral tegmental area
      have been implicated in reward-related functions. These neurons are excited by
      reward and sensory stimuli that predict reward and inhibited by reward omission.
      These excitatory and inhibitory responses are thought to guide reward-seeking
      behaviors. Indeed, reward-seeking behaviors can be impaired by injecting dopamine
      antagonists into the brain areas targeted by dopamine neurons (e.g., caudate
      nucleus). However, it was unknown which parts of the brain provide dopamine
      neurons with reward-related signals necessary to induce their responses. Recent
      studies showed evidence that the lateral habenula, a part of the structure called
      the epithalamus, is a good candidate for a source of reward-related signals in
      dopamine neurons. The lateral habenula projects to midbrain structures such as
      the substantia nigra pars compacta and ventral tegmental area which contain
      dopamine neurons. Electrical stimulation of the lateral habenula inhibits the
      activity of dopamine neurons. Neurons in the lateral habenula also encode reward
      related signals but in a manner opposite to that obeerved for dopamine neurons
      (i.e., lateral habenula neurons are inhibited by reward and sensory stimuli
      predicting reward and excited by reward omission). These anatomical and
      physiological findings suggest that the lateral habenula transmits reward-related
      signals to dopamine neurons by inhibiting them. Thereby, the lateral habenula
      could contribute to reward-seeking behaviors through its projections to the
      dopaminergic systems.

PMID- 19378809
TI  - [Reward processing of the basal ganglia--reward function of pedunculopontine
      tegmental nucleus].
AB  - We address the role of neuronal activity in the pathways of the brainstem
      midbrain circuit in reward and the basis for the hypothesis that this circuit
      provides advantages over previous reinforcement learning theories. Several lines
      of evidence support the reward-based learning theory proposing that midbrain
      dopamine (DA) neurons emit a teaching signal (the reward prediction error signal)
      to control synaptic plasticity of the projection area. However, the underlying
      mechanism of the location and manner in which the reward prediction error signal
      is computed remains unclear. Since the pedunculopontine tegmental nucleus (PPTN)
      in the brainstem is one of the strongest excitatory input sources to DA neurons,
      we hypothesized that the PPTN may play an important role in activating the DA
      neurons and reinforce learning by relaying necessary signals for reward
      prediction error computation to those neurons. To investigate the involvement of
      PPTN neurons in reward prediction error computation, we employed a visually
      guided saccade task while recording the neuronal activity in monkeys. Here, we
      predict that PPTN neurons may relay the excitatory component of tonic reward
      prediction and phasic primary reward signals, and derive a new computational
      theory of reward prediction error in DA neurons.

PMID- 19378810
TI  - [Reinforcement learning by striatum].
AB  - Recently, computational models of reinforcement learning have been applied for
      the analysis of neuroimaging data. It has been clarified that the striatum plays
      a key role in decision making. We review the reinforcement learning theory and
      the biological structures such as the brain and signals such as neuromodulators
      associated with reinforcement learning. We also investigated the function of the
      striatum and the neurotransmitter serotonin in reward prediction. We first
      studied the brain mechanisms for reward prediction at different time scales. Our
      experiment on the striatum showed that the ventroanterior regions are involved in
      predicting immediate rewards and the dorsoposterior regions are involved in
      predicting future rewards. Further, we investigated whether serotonin regulates
      both the reward selection and the striatum function are specialized reward
      prediction at different time scales. To this end, we regulated the dietary intake
      of tryptophan, a precursor of serotonin. Our experiment showed that the activity
      of the ventral part of the striatum was correlated with reward prediction at
      shorter time scales, and this activity was stronger at low serotonin levels. By
      contrast, the activity of the dorsal part of the striatum was correlated with
      reward prediction at longer time scales, and this activity was stronger at high
      serotonin levels. Further, a higher proportion of small reward choices, together
      with a higher rate of discounting of delayed rewards is observed in the low
      serotonin condition than in the control and high-serotonin conditions. Further
      examinations are required in future to assess the relation between the
      disturbance of reward prediction caused by low serotonin and mental disorders
      related to serotonin such as depression.

PMID- 19378811
TI  - [Functional analysis of the roles of direct and indirect pathways by using
      immunotoxin-mediated cell targeting approach].
AB  - The neural circuit connecting the cerebral cortex and the basal ganglia mediates
      a variety of brain functions including voluntary movement, motor learning, and
      reinforcement learning. These functions are dependent on midbrain dopamine
      systems that innervate the prefrontal cortex and the striatum. The pathogenesis
      of certain neurological and neuropsychiatric diseases involves the dysfunction of
      these dopamin systems; some of these diseases include Parkinson's disease,
      schizophrenia, and attention deficit hyperactivity disorder. To understand the
      physiology and pathology of brain functions, the mechanisms of neural circuitry
      that controls behaviors should be studied. Immunotoxin-mediated cell targeting is
      an approach employed in transgenic animals to eliminated specific neuronal types
      from a neuronal circuitry. This approach has been used to study the neural
      circuit mechanism in the central and peripheral nervous systems. Here, we
      describe the use of immunotoxin-mediated cell targeting for studying the neural
      circuitry that underlies the motor behavior demonstrated in response to systemic
      dopamine stimulation; further, we propose the potential mechanism that controls
      direct and indirect striatal pathway-dependent behavior.

PMID- 19378812
TI  - [Functions of the septin cytoskeleton and its roles in dopaminergic
      neurotransmission].
AB  - Cytoskeletal polymers are component of cellular infrastructure that are required
      for fundamental biological processes ranging from cell division to brain
      functions. Unlike the knowledge available for tubulin and actin, our
      understanding of unconventional cytoskeletal structures composed of GTP-binding
      proteins belonging to the septin family is limited, despite their ubiquity and
      implications in human diseases. Recent studies have revealed that septin plays
      unique modulatory roles as an accessory component of microtubules and the actin
      cytoskeleton. Morphological analyses of the mammalian brain and neural cells have
      revealed that septins preferentially cluster beneath the extra-synaptic membrane
      domains in dendritic shafts and spine necks, presynaptic terminals of major
      neurons, and astroglial processes. Live imaging analysis revealed that septin
      polymers are remarkably stable in these clusters, which may serve as local
      cytoskeleton and/or scaffold for the organization of specialized cortical domains
      in neurons and glia. This hypothesis has been supported by the hypo-dopaminergic
      phenotype of mice that lack the Sept4 subunit and the hyper-dopaminergic
      phenotype of those with excess Sept4. In these cases, the septin scaffold in the
      dopamine neurons is considered as a determinant of the quantity of a subset of
      presynaptic molecules, including tSNAREs (membrane-fusion machinery) and the
      dopamine transporters. This finding in mouse models is in agreement with the
      recent findings that qualitative and/or quantitative dysregulation of septins is
      involved in neurodegenerative disorders such as Parkinson disease and
      psychological disorders such as schizophrenia and bipolar disorder. Studies on
      tubulin/actin indicate that a better understanding of the septin family of
      proteins will improve our insight into neuropathological phenomena in
      neurodegenerative and psychological disorders, which may help develop diagnostic
      markers and therapeutic strategies for such diseases.

PMID- 19378813
TI  - [Pathology of basal ganglia in neurodegenerative diseases].
AB  - Intra- and/or extracellular proteinaceous inclusions in the brain tissue are
      characteristic pathological markers of many neurodegenerative diseases. Tau
      protein in neurofibrillary tangles and beta-amyloid in senile plaques are
      associated with Alzheimer's disease. Tau is associated with various neurological
      conditions, which are collectively referred to as tauopathies. Alpha
      synucleinopathy is a term that collectively refers to a set of diseases in which
      neurodegeneration is accompanied by intracellular accumulation of alpha-synuclein
      in neurons or glial cells. Recently, TDP-43 has been identified as a major
      disease protein in the ubiquitinated inclusions in deseases such as amyotrophic
      lateral sclerosis and frontotemporal lobar degeneration with tau-negative,
      ubiquitin-positive inclusions. Thus, these neurodegenerative disorders comprise a
      new disease class, namely, TDP-43 proteinopathy. In this article, we review the
      present understanding of histopathological features of basal ganglia lesions in
      protein conformation disorders, including tauopathy, alpha-synucleinopathy, and
      TDP-43 proteinopathy.

PMID- 19378814
TI  - [Pathological mechanisms of Parkinson's disease].
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease. It
      is associated with the degeneration of dopaminergic neurons in the substantia
      nigra pars compacta and other areas of the brain. The pathology of PD is
      characterized by the accumulation of a cytoplasmic fibrillar structure, wherein
      alpha-synuclein is the major component. Most occurrences of PD were believed to
      be sporadic and associated with aging and environmental stress. However, there is
      now strong evidence for genetic inheritance in a small number of families.
      Although the pathological mechanisms of PD are still largely unknown, we present
      the major hypotheses and discuss the future directions of studies in this area.

PMID- 19378815
TI  - [Causative gene and its associated gene for Parkinson disease and dystonia].
AB  - Parkinson disease (PD) and dystonia are two major part of neurodegenerative
      disorders. The underlying cause of PD development has been considered to be a
      combination of genetic factors and environmental substrates. In case of dystonia,
      which includes primary sporadic dystonia, such as task specific dystonia,
      cervical dystonia and so on, are also considered to associate with unknown
      vulnerable genetic factors. In this paper, the clinical features and causative
      genes for PD and dystonia were described; especially in particular, the
      description of those genes associated with the PARK and DYT series were provided.
      Most of the identified causative genes for PD are associated with the protein
      degradation and cell death process via convergent mechanisms such as ubiquitin
      proteasome system, mitochondrial dysfunction, oxidative stress, and lysosomal
      system (autophagia). On the other hand, the pathogenic mechanism for dystonia is
      gradually discovered to be divergent suggested by identified genes, such as
      torsinA, GCH1, etc, which is compatible and well understood with the divergent
      expression of dystonia phenotype. Another breakthroughs are required to
      investigate the treatment of both PD and dystonia based on the pathogenic
      mechanisms.

PMID- 19378816
TI  - [Pharmacologic treatment of Parkinson disease].
AB  - In this paper, I have discussed a modification in the current treatment strategy
      for Parkinson disease (PD) and the application of a new drug, zonisamide, for the
      treatment of PD. At the beginning of the 21st century, the following views were
      held strongly regarding the treatment of PD (1) L-dopa may be toxic, (2) dopamine
      agonist may exert neuroprotective effects, (3) dopamine agonists should be used
      as the initial treatment for parkinsonian patients without dementia or psychosis.
      However, the paradigm has now been modified to state (1) L-dopa does not
      accelerate disease progression, (2) no treatment modality exerts neuroprotective
      effects, (3) L-dopa is more effective than dopamine agonists in alleviating motor
      symptoms and improving the activities of daily living (ADL) score, in
      parkinsonian patients. Treatment with dopamine agonist is associated with fewer
      motor complications than L-dopa. Dopamine agonist therapy is associated with more
      frequent adverse events than L-dopa therapy, such as hallucinations and
      somnolence. There is no evidence of a long-term benefit with initial dopamine
      agonist therapy. Therefore, the treatment should be determined on a case-by-case
      basis. Furthermore, some clinical trials have indicated that early dopaminergic
      support for the degenerating dopaminergic system offers significant long-term
      clinical benefits for parkinsoninan patients. Zonisamide (25-50mg/day) improves
      motor functions and wearing-off without worsening dyskinesia in advanced cases of
      Parkinson disease. Furthermore, zonisamide affects an increases in the levels of
      glutathione and manganese superoxide dismutase expression and, it ameliorates
      reduction in the number of dopaminergic neurons in mice treated with
      6hydroxydopamine (6-OHDA). Zonisamide may exert neuroprotective effects in
      parkinsonian patients.

PMID- 19378817
TI  - [Deep brain stimulation for Parkinson's disease and dystonia].
AB  - Deep brain stimulation (DBS) has proved highly effective in the treatment for
      Parkinson's disease and dystonia. Presently, many types of dopamine agonists,
      monoamine oxidase B (MAOB) inhibitors, catechol-O-methyltransferase (COMT)
      inhibitor or other antiparkinsonian drugs are being developed. However, it is
      still very difficult to medically treat motor complications associated with
      levodopa therapy. Surgical intervention using DBS was possible to stimulate the
      subthalamic nucleus as the treatment of Parkinson's disease. Stimulation of the
      subthalamic nucleus improves the cardinal parkinsonian symptoms and motor
      complication associated with levodopa treatment. DBS is a reversible treatment
      and the original status could be observed by turning off the stimulation. This
      procedure enables the observation of clinical outcomes or brain mechanisms under
      both the conditions of turned on and turned off stimulations. On the other hand,
      dystonia is heterogeneous and refractory and hence, it has been difficult to
      medically treat it. Since there was no effective treatment available for patients
      with generalized dystonia, these patients became disabled. However, recently,
      bilateral pallidal DBS has been shown to markedly improve the conditions of
      patients with generalized dystonia, and it has proven to be a reliable treatment.
      There are two characteristic clinical effects of pallidal DBS on dystonia. It
      improves primary hereditary generalized dystonia, particularly DYT 1, more
      prominently than secondary dystonia and its beneficial effects are observed over
      a period of time course. The beneficial effects of pallidal DBS in patients with
      dystonia are not immediate but progress over weeks to months. The brain mechanism
      underlying the improvement of pallidal DBS in dystonia has been unclear. Many
      studies on DBS in Parkinson's disease and dystonia have been carried out to
      elucidate the clinical outcomes and/or the underlying neurophysiological
      mechanisms. In this review, the clinical outcomes of DBS for Parkinson's disease
      and dystonia will be focused on.

PMID- 19378818
TI  - [Current status of gene therapy for Parkinson disease].
AB  - Gene therapy is particularly appropriate for Parkinson disease (PD) since this
      condition exclusively affects the dopaminergic neurons projecting from the
      substantia nigra pars compacta (SNc) to the putamen. Currently, 4 ongoing phase I
      clinical trials are utilizing recombinant adeno-associated viral vectors (rAAv)
      or lentivirus vectors for the treatment of PD. In this article, we describe
      recent progress in the development of gene therapy methods for PD by reviewing
      clinical trials in this field. Parkin-associated PD is recessively inherited,
      that is, loss of function of parkin leads to the development of parkin 
      associated PD; hence, substrates for parkin (for its E3 function) are expected to
      accumulate in the brain. Therefore, the replacement of parkin function in such
      patients would decrease the toxicity of these substrates. We previously found
      that the transfer of parkin, encoding a familial PD-linked E3 ubiquitin ligase,
      in rats with PD could prevent the degeneration of nigral dopaminergic neurons. In
      addition, we recently reported the case report of a preclinical examination of
      rAAV vector-mediated retrograde delivery of parkin into nigrostriatal
      dopaminergic neurons in a non-human primate. In this article, we also review the
      potential of parkin gene therapy for the treatment of PD patients.

PMID- 19378819
TI  - [Case of callosal disconnection syndrome with a chief complaint of right-hand
      disability, despite presence of left-hand diagonistic dyspraxia].
AB  - e report the case of 48-year-old right-handed male patient with an infarction
      affecting most part of the body and the splenium of the left half of the corpus
      callosum. Neuropsychological examination revealed typical signs of callosal
      disconnection including left-sided apraxia, diagonistic dyspraxia, left-sided
      agraphia, left-hand tactile anomia, left hemialexia, and right-sided
      constructional disability. Moreover, he complained of impairment in activities
      involving the right hand disability and agraphia. He could not stop behaving with
      his right hand when he had a vague idea. For example, he involuntarily picked up
      a tea bottle with his right hand when he had a desire to drink, although the
      action was not appropriate to that occasion. The imitation and utilization
      behavior did not imply this case, because his right hand behaviors were not
      exaggerated in response to external stimuli, such as the gestures of the examiner
      or the subjects in front of the patient. Unexpectedly, he complained about
      impairment of the activity of his right hand and was unaware of left hand apraxia
      or diagonistic dyspraxia; this trend continued for 6 months, at the time of this
      writing. We argue that the patient may have been subconsciouly aware of the
      symptoms of his left hand but had not verbalized them.

PMID- 19378820
TI  - [One hundred books which built up neurology (28)--Hermann Boerhaave "Opera Omnia
      Medica" (1735)].

PMID- 19378821
TI  - [Severe hypoglycemia after resection of adrenal pheochromocytoma: a case report].
AB  - A 55-year-old female presented with subarachnoid hemorrhage and was admitted to
      the department of neurosurgery. Because she had severe hypertension, systemic
      evaluation was performed. Computed tomography showed a right adrenal tumor which
      was suspected to be a pheochromocytoma because catecholamine levels were very
      high in both serum and 24-hour urine. She did not awaken from anesthesia after
      laparoscopic adrenalectomy and laboratory tests showed that her blood sugar
      concentration was 33 mg/dl. This hypoglycemia was controlled by continuous
      infusion of a 50% glucose solution at 40 ml/h and she became conscious the next
      morning. We gradually decreased the amount of glucose infused and stopped the
      infusion on postoperative day 4. The tumor was pathologically diagnosed as a
      pheochromocytoma.

PMID- 19378822
TI  - [A case of retroperitoneal schwannoma treated by laparoscopic resection].
AB  - We report a case of retroperitoneal schwannoma treated by laparoscopic surgery. A
      32-year-old woman presented with a mass in the retroperitoneal space that was
      incidentally revealed by abdominal echography. Computed tomography and magnetic
      resonance imaging showed a mass 95 mm in diameter in the retroperitoneal cavity
      which had a cystic component. With a diagnosis of retroperitoneal tumor,
      laparoscopic resection was performed. Pathological diagnosis was retroperitoneal
      benign schwannoma consisting of Antoni A and B types. Our case is the largest
      retroperitoneal schwannoma tumor which was removed by laparoscopic surgery.

PMID- 19378823
TI  - [Solitary metastasis of renal cell carcinoma to the contralateral ureter: a case
      report].
AB  - A 79-year-old woman presented with gross hematuria. She had undergone a right
      radical nephrectomy 2 years previously for G2 pT2 renal cell carcinoma, clear
      cell variant. Intravenous pyelography showed a filling defect in the left ureter.
      Systemic work-up demonstrated no evidence of other metastases. Partial uretectomy
      and end-to-end ureteroureterostomy were performed. Histology showed metastatic
      clear cell carcinoma consistent with the primary renal tumor. Six months after
      surgery, her serum creatinine was stable at 1.6 mg/dl and she was doing well
      without evidence of recurrent disease. Solitary metastasis of renal cell
      carcinoma to the contralateral renal pelvis or ureter is extremely rare, with
      only 7 cases having been reported. We herein describe the present case and review
      the relevant literature.

PMID- 19378824
TI  - [Gastric metastasis from renal cell carcinoma 20 months after radical
      nephrectomy: a case report].
AB  - Metastatic lesions from renal cell carcinoma (RCC) commonly occur in the lung and
      bone, gastric metastasis has rarely been reported in the literature. We present
      herein a case of a man with gastric metastasis from RCC. A 49-year-old male was
      admitted to our hospital complaining of dyspnea on exercise. He had undergone
      right radical nephrectomy due to RCC two years ago (T3a NO MI), followed by
      postoperative immunotherapy with interferon-alpha and interleukin 2.
      Gastrointestinal endoscopy revealed a solitary polypoid lesion about 20 mm in
      diameter in the greater curvature of the middle gastric body. Endoscopic needle
      biopsy revealed poorly differentiated adenocarcinoma. Partial gastrectomy was
      performed and histologic examination of the resected specimen confirmed diagnosis
      of clear cell renal carcinoma. Metastasis of any cancer to the stomach is quite
      uncommon. In particular, gastric metastasis from RCC is extremely rare. To our
      knowledge, this is the 15th case of gastric metastasis from RCC reported in
      Japan.

PMID- 19378825
TI  - [Port-site metastasis of an upper urinary tract urothelial carcinoma after
      laparoscopic nephroureterectomy: a case report].
AB  - We report here a case of ureteral cancer in which port-site metastasis was
      suspected after a nephroureterectomy. The patient was a male in his fifties with
      a chief complaint of asymptomatic gross hematuria. A tumor was found in his left
      renal pelvis and ureter by a computed tomographic (CT) scan. The patient was
      diagnosed with a left upper urinary tract cancer with a clinical stage of T2N0M0.
      A left laparoscopic nephroureterectomy was performed through a retroperitoneal
      approach. Lymph node dissection was performed with an ultrasonic surgical knife.
      The pathological diagnosis was an urothelial carcinoma, grade 2 > 3, INFbeta,
      pT3, pV1, pN2. He received two courses of MVAC chemotherapy (methotrexate 50 mg,
      vinblastine 5 mg, adriamycin 50mg, cisplatin 120 mg) postoperatively. Since
      retroperitoneal lymph node metastasis was observed three months later on a CT
      scan, the MVAC chemotherapy was repeated for three courses. Nine months later, a
      tumor was found in the hypodermic beside the port-site, and a needle biopsy
      confirmed a metastatic urothelial carcinoma. He received two courses of GP
      chemotherapy (gemcitabine 4,250 mg, paclitaxel 225 mg). He died of multiple
      metastases five months later.

PMID- 19378826
TI  - [An adenocarcinoma arising from the urinary bladder 37 years after bladder
      augmentation using the ileum].
AB  - A 57-year-old man had undergone right nephrectomy at 10 years of age and bladder
      augmentation using the ileum at 20 years for treatment of urinary tract
      tuberculosis. He also had undergone intermittent catheterization after a traffic
      accident at 49 years of age. He presented at another hospital with a complaint of
      asymptomatic macroscopic hematuria. Cystoscopy revealed a lobulated tumor in the
      bladder. Transurethral resection of bladder tumor was performed, but complete
      resection was difficult. Histopathological examination of the specimen revealed a
      well differentiated adenocarcinoma. He was referred to our hospital for total
      cystectomy and percutaneous left nephrostomy. The tumor arose from the bladder
      wall near the anastomotic site between the bladder and the ileal segment.
      Histopathological examination revealed a well differentiated adenocarcinoma
      infiltrating into the muscle layer (pT2a). Postoperatively, he has been free of
      recurrence for one year. This is the 19th case of adenocarcinoma following
      bladder augmentation using the ileum reported in the Japanese literature.

PMID- 19378827
TI  - [A case of penile metastasis of malignant melanoma with priapism].
AB  - A metastatic penile tumor of malignant melanoma is very rare. The patient had
      priapism caused by metastatic penile tumor and the primary cancer was in the end
      stage. However, in this case, we could relieve the dysuria and pain by
      percutaneous cystostomy and partial penectomy. The corpus spongiosumcorpus
      cavernosum shunt could not relieve the priapism and might have accelerated the
      metastasis.

PMID- 19378828
TI  - [Localized Fournier's gangrene of the penis: a case report].
AB  - Fournier's gangrene is a rare disease with rapidly progressive necrotising
      fasciitis of the genital, perineal and perianal regions and leads to sepsis and
      death. We reported a case of localized Fournier's gangrene of the penis. A 23
      year-old man suffered an abrasion of the penis during oral sex with a commercial
      sex worker. Because pain as well as redness and swelling appeared on the penile
      surface, he consulted the nearest hospital. Since Fournier's gangrene was
      suspected, he was admitted to our hospital. According to the clinical symptoms
      and diagnostic imaging by using magnetic resonance imaging, we diagnosed
      Fournier's gangrene. Immediately, we started broad-spectrum antibacterial
      chemotherapy and performed debridement. The postoperative course was good and
      then the open wound was closed with artificial corium and full thickness skin
      graft to avoid erectile disturbance.

PMID- 19378829
TI  - [Segmental testicular infarction--a case report].
AB  - A 31-year-old male visited our hospital with a complaint of left scrotal pain
      that began suddenly one week before the visit. The results of scrotal
      examination, blood cell count and biochemical examination were normal. Enhanced
      magnetic resonance imaging (MRI) showed a well-defined avascular lesion of the
      left testis with rim enhancement. With the suspicion of a segmental testicular
      infarction, left testicular biopsy and bilateral orchiopexy were performed.
      Pathological examination demonstrated a testicular infarction. One month after
      surgery, enhanced MRI showed normal testis.

PMID- 19378830
TI  - [Testicular cavernous hemangioma associated with intrascrotal testicular torsion:
      a case report].
AB  - A 22-year-old man consulted our hospital with a left intrascrotal mass and a six
      day history of dull pain in the left lower abdomen. Serum levels of tumor markers
      were normal. Testicular ultrasonography demonstrated a heterogeneous isoechoic
      mass in the left testis. Computed tomography revealed a left testicular mass with
      high density. A diagnosis of probable testicular malignancy was made, and left
      radical orchiectomy was performed. Intraoperative findings indicated torsion of
      the left testis. The testis was necrotic and the mass including the testis was
      extirpated. The histopathological diagnosis was testicular cavernous hemangioma.
      To our knowledge, only 20 cases of cavernous hemangioma of the testis have been
      reported to date, and this is the first report of testicular hemangioma
      presenting with torsion of the testis.

PMID- 19378831
TI  - Risk factors associated with symptomatic hypoglycemia in type 2 diabetes mellitus
      patients.
AB  - OBJECTIVE: To identify risk factors associated with symptomatic hypoglycemia (SH)
      (< or = 72 mg/dL) in patients with type 2 diabetes mellitus (t2DM) treated at a
      general hospital during July 2003 to December 2004. MATERIAL AND METHODS: Ninety
      four t2DM patients (incident cases) with a primary diagnosis of SH matched with
      188 t2DM patients (incident controls) with a diagnosis other than hypoglycemia
      were included in a case-control study. Demographic and clinical variables entered
      into an automated binary logistic regression model from which odds ratio (OR) and
      95% confidence intervals (95% CI) for variables with a p value < 0.05 were
      obtained. RESULTS: The binary logistic model determined that age had a
      "protective" effect, while duration of t2DM, educational level (Illiteracy
      primary education, OR 3.7, [95% CI 1.4 to 10]; p = 0.009), attending physicians'
      specialty (family physician, OR 2.8, [1.02 to 7.9]; p = 0.04), chronic renal
      failure presence (OR 3.0, [1.2 to 7.7]; p = 0.01), antihyperglycemic treatment
      (combined therapy, OR 5.2, [2.3 to 11.8]; p < 0.01), fasting (OR 19.8, [9.1 to
      43.1]; p < 0.001) and history of hypoglycemia (OR 2.9, [1.3 to 6.5]; p = 0.01)
      were all risk factors associated with SH. The variable "exposure to polypharmacy"
      was excluded from the logistic model (OR 4.86; [0.7 to 35.1]; p = 0.11).
      CONCLUSIONS: According to our results, physicians should be cognizant of the
      possibility that the odds of SH might be increased when treating patients with
      t2DM fulfilling factors, such as those identified in this investigation.

PMID- 19378832
TI  - [Acute lymphoblastic leukemia: experience in adult patients treated with
      hyperCVAD and 0195 Protocol, at the Instituto Nacional de Ciencias Medicas y
      Nutricion Salvador Zubiran. Cohort 2003-2007].
AB  - INTRODUCTION: Despite therapeutic advances, acute lymphoblastic leukemia (ALL) in
      adults remains a disease with poor long term outcome and survival rates.
      Developing countries lack of information about this disease. On the other hand,
      infections are frequent complications related to mortality and some research
      studies do not show accurate rates of septic shock or other related factors.
      OBJECTIVE: To describe characteristics of adults with acute lymphoblastic
      leukemia, response to treatment, complications and to evaluate further survival
      related factors and to compare our experience with other reports of literature.
      MATERIAL AND METHODS: Between September 2003 to November 2007, the entire cohort
      of patients with diagnosis of ALL was included. The treatment regimens used were
      MDACC HyperCVAD (HCVAD) and 0195 (institutional regimen). RESULTS: Of 40 patients
      included with the diagnosis of ALL, 92% was B phenotype and 8%, T phenotype, with
      a median age of 27 years. The median follow up was 28.5 months. Initially, 14%
      showed central nervous system infiltration; of 51% with available cytogenetics,
      16.7% was Philadelphia chromosome positive. There were 36 patients who received
      treatment: 13 received HCVAD and 23 the 0195 protocol; 78% achieved global
      complete remission, 85% for the patients with HCVAD and 74% with 0195. The
      induction death rate was 2.8%. The median disease-free survival was 11.6 months
      (IC 95%, 2.5-20.8 months) and overall survival was 15 months (IC 95%, 10.6-19.4
      months). In 95% of patients, no prophylactic antibiotic therapy was used and
      treatment related death was 8.4% (2.8% during induction and 5.6% during the rest
      of treatment). Factors associated with worse survival rate were
      hyperleukocytosis, T phenotype and lack of early complete remission. During
      induction, grade 3 to 4 non hematopoietic toxicity was 17%. Incidence of
      neutropenic febrile episodes was 61% and septic shock was 11%. CONCLUSIONS: With
      HCVAD, we observed worse complete remission, disease-free survival and overall
      survival rates compared with the original MDACC reports. Chemotherapy related
      death rates are similar to other early reports, despite prophylactic antibiotic
      was not used during myelosuppression.

PMID- 19378833
TI  - A primary Helicobacter pylori infection does not protect against reinfection in
      children after eradication therapy.
AB  - BACKGROUND: Helicobacter pylori infection is one of the most common chronic
      infections in the world, and is acquired mainly during childhood. It is not clear
      to which extent a primary infection protects the child from reinfection. Our aim
      was to determine the possible protection conferred by a primary infection against
      H. pylori reinfection in children. METHODS: A follow-up study with 120 children
      distributed in two cohorts; the first included 80 children without previous H.
      pylori infection (primo-infection cohort); the second included 40 infected
      children successfully eradicated (reinfection cohort). Cohorts were monitored
      during 2 years with urea-breath-test (UBT) at 3, 6, 9, 12, 18 and 24 months for
      the acquisition of H. pylori infection. We compared the rate of reinfection in
      eradicated children with the rate of infection in children without previous
      infection. H. pylori infection during the follow-up was analyzed and compared
      between cohorts using chi2 and survival curves. A questionnaire was performed for
      the evaluation of possible risk factors for infection in both cohorts. RESULTS:
      No significant differences in rates of primo-infection or reinfection were found;
      17 (21.2%) primo-infections and 10 (25%) reinfections were documented. Most of
      the primo-infections (14/17) occurred in the first year of follow-up. In
      contrast, reinfection episodes occurred more frequently during the second year
      (6/10). In both cohorts, most infections were transient. Risk factors were
      similar for both, primo and reinfection cohorts. CONCLUSION: A primary infection
      does not protect from reinfection in the population of children studied.

PMID- 19378834
TI  - [Menstrual cycle perception and psychological distress in a sample of Mexican
      women].
AB  - OBJECTIVE: To evaluate the association between psychological distress and
      menstrual bleeding perception, in order to design a psychological intervention
      for women in reproductive age. MATERIAL AND METHODS: Ex post facto and
      retrospective study in a random sample of women living in Mexico City with ages
      between 15 to 35 years. The following instruments were administered after reading
      the informed consent form: demographic and social questionnaire, gyneco-obstetric
      clinical history, menstrual bleeding diagnostic scale, menstrual bleeding
      analogical scale and the Goldberg's General Health Questionnaire. RESULTS: 909
      women were interviewed and 776 completed the study. A significant statistic
      association existed between the presence of menorrhagia and the symptoms of
      psychological distress. CONCLUSIONS: Our results suggest a temporary interaction
      between physiological and psychological symptoms that produce an intense sense of
      distress in the women.

PMID- 19378835
TI  - [The educational reach of discussion in small groups. The role of the professor's
      differential experience].
AB  - INTRODUCTION: The teachers' formation program at IMSS includes the methodological
      diplomate in teaching level I (DMDI) and level II (DMDII). This program is based
      in educational strategies that promote the participation (guide towards knowledge
      elaboration). The importance of discussion in small groups (subgroups) to
      increase learning has been showed as part of such strategies. OBJECTIVE: To
      evaluate the influence in learning of the professors' experience in coordinating
      the subgroup discussion. MATERIAL AND METHODS: Three groups of students were
      included (professors in teaching formation) that had consecutively studied the
      DMDI: DMDIa, DMDIb, and DMDIc. There was also included a group of DMDII whose
      students had participated in DMDI as coordinators of the subgroup discussion of
      DMDIb and DMDIc (DMDIa did not count with coordinators). Two instruments
      previously validated were used to evaluate the development of a position about
      education and scientific work (indicator of both: % of consequence). Evaluations
      were made at the beginning and end of each DMDI. RESULTS: Position in education:
      at the beginning DMDIa = 36; DMDIb = 30, DMDIc = 31, without differences among
      them (p 0.65). After the interventions the increases were: DMDIa from 36 to 75 (p
      < 0.01), DMDIb from 30 to 91 (p < 0.01), DMDIc from 31 to 90 (p < 0.01). When
      comparing the groups among themselves, differences were found between DMDIa and
      DMDIb, DMDIa and DMDIc, and no differences were found between DMDIb and DMDIc.
      Position about scientific work: at the beginning DMDIa = 20; DMDIb = 14; DMDIc =
      15 (p. 0.35). After the interventions the increases were: DMDIa from 20 to 35 (p
      < 0.05); DMDIb from 14 to 53 (p < 0.02), DMDIc from 15 to 79 (p < 0.001). When
      comparing the groups among themselves, difference was found between DMDIb and
      DMDIc (p < 0.02) and from these two and DMDIa. DISCUSSION: The results support
      the hypothesis that the professor's experience in the coordination of subgroup
      discussion has a notorious influence in learning. The DMDIa group that did not
      have this support showed lower advances with both instruments. The DMDIb group
      that had coordinating professors with little experience had equivalent advances
      to DMDIc in position about education, and lower advances in the position about
      scientific work. The DMDIc group whose coordinating professors had a previous
      experience with the DMDIb group showed the greatest increases. Features of
      educational strategy promoting the participation are described as well as the
      importance of the experience of the professor in coordinating the discussion, to
      increase learning.

PMID- 19378836
TI  - [Osteogenesis of human vascular endothelial cells in culture].
AB  - INTRODUCTION: Mesenchymal stem cells have the potential to differentiate into
      several types of cells including osteoblasts. These stem cells have cell surface
      markers found on cells of endothelial and subendothelial origin of the umbilical
      cord vein. Taking this into consideration we have postulated that human umbilical
      vein endothelial cells (HUVEC) could present osteogenic differentiation as well.
      Gene activation that could drive osteogenic differentiation is regulated by
      exogenous and endogenous factors. OBJECTIVE: The induction osteogenesis in HUVEC.
      MATERIAL AND METHODS: We used: a) an osteogenic medium containing 0.1 microM
      dexamethasone, 10 microM beta-glycerophosphate, 50 microM L-ascorbic-acid 2
      phosphate, 20% MCGS serum; and b) a treatment with DNA demethylating agents
      hydralazine and 5'-aza-2'-deoxycytidine (0.39-200 microM). Phenotypic
      characteristics of HUVEC were their spindle and stellate shapes with fine
      homogenous cytoplasm, typically associated with fibroblast-like cells. RESULTS:
      The control cells (without osteogenic treatment) exhibited little extracellular
      matrix, whereas the osteogenically treated cells appeared shortened and
      flattened, and they were surrounded by extracellular matrix that subsequently
      became mineralized in vitro. After 28 days in culture, morphologic and
      histochemical studies confirmed that osteogenic medium had a strong stimulatory
      effect on the alkaline phosphatase activity of endothelial cells, a very early
      marker of cell differentiation into the osteogenic lineage. Hydralazine and 5'
      aza-2'-deoxycytidine, two drugs utilized in chromatin remodeling leading to gene
      re-expression of inactivated DNA hypermethylated islands, did not favor
      osteoblast differentiation. CONCLUSION: Our study shows that HUVEC can
      differentiate along an osteogenic lineage and thus provide an alternative source
      for cell-based therapies and tissue engineering strategies.

PMID- 19378837
TI  - [Mechanisms of cardiovascular damage in obstructive sleep apnea].
AB  - Obstructive sleep apnea syndrome (OSAS) is an independent and modifiable risk
      factor for cardiovascular diseases; however, the pathophysiological mechanisms
      underlying this association are not yet fully understood. Intermittent hypoxemia,
      one of the physiological markers of OSAS, is characterized by transient periods
      of oxygen desaturation followed by reoxygenation. The cycles of hypoxia
      reoxygenation are associated with oxidative stress that, in turn, triggers the
      activation of pathways that lead to cardiovascular damage. These pathways include
      an increased chemoreflex sensitivity that induces the over-activation of the
      sympathetic nervous system, decreased baroreflex sensitivity, the activation of
      systemic inflammation pathways mediated primarily by the nuclear transcriptional
      factor kappaB that favors the development of atherosclerosis through the
      synthesis of cytokines and the expression of adhesion molecules, endothelial
      dysfunction with a decreased availability of nitric oxide, dyslipidemia, insulin
      resistance and stimulation of the renin-angiotensin system. Other mechanisms
      proposed include arousals that increase sympathetic activity and exaggerated
      intrathoracic pressure changes that generate high transmural pressure. Most of
      these mechanisms respond favorably to treatment with CPAP. A better understanding
      of the mechanisms of cardiovascular damage opens the possibility of instituting
      new treatments that will contribute to limiting the cardiovascular consequences
      associated with OSAS.

PMID- 19378838
TI  - [The role of primary physicians in the early detection and treatment of chronic
      renal disease: challenges and opportunities].

PMID- 19378839
TI  - [The cultural history of disease].
AB  - In this essay the concept of Cultural History of Disease (CHD) is proposed as an
      alternative to Natural History of Disease (NHD). A brief historic recapitulation
      of the concept of disease is made, and the present idea is given a detailed
      account which is the basis of the nosological theory of the health/disease
      paradigm. The main aspects of the NHD are specified, its limitations and
      restrictive consequences in health care are highlighted. It is proposed the idea
      of disease as particular and differential ways of being from human beings. It is
      showed how culture (everything that make us human) "takes the reins of evolution"
      in our species and determines, in every period, our ways of being, of living, and
      getting sick. Some distinctive qualities of life are showed to take a distance
      from the idea of machine and the dominant mechanism of health care in our time.
      The concept of CHD is developed as a proposal that "lightens" aspects ignored by
      NHD. An account is made of how, by cultural effect, a number of diseases no
      longer exist; others have appeared or increased their presence, have changed
      their features or varied their distribution. The every time more and more
      unsupported congenital/acquired dichotomy is discussed. It is showed how the
      epigenetic inheritance is a strong evidence against the separation between
      genetic and environmental. The mechanist causality, in its different
      characteristics, proper of the health/disease paradigm and of NHD, is contrasted
      to contextual causality proper of CHD. The implications of CHD in the way of
      approaching to diseases, in restating the patients', physicians' and health care
      institutions' role are discussed. As well as in recognizing that health care has
      no sense without life care in its different manifestations, from which derives
      the need to fight for more proper conditions and circumstances for a dignified,
      satisfactory, serene, fraternal life in including societies.

PMID- 19378840
TI  - [Comments to the manuscript; HIV in Mexican blood donors and estimated
      transfusional risk].

PMID- 19378841
TI  - Autologous bone marrow stem cell transplantation in patients with end-stage
      chronical critical limb ischemia and diabetic foot.
AB  - A total 37 patients suffering from end stage-IV Fontaine (CLI and diabetic foot)
      with an ulcerated limb in whom all previous therapeutic strategies failed (e.g.
      surgical revascularization and endovascular repair) were selected and underwent
      local transplantation of Autologous Bone Marrow Stem Cells (ABMSCs). The
      efficacy/safety ofthis therapy was assessed by using several endpoints such as
      (a) prevention of amputation, (b) wound healing and (c) degree of angiogenesis.
      In order to assess the limb ischemia and hypoxia the several tests and
      measurements were performed pre- and post transplantation at a variety of time
      intervals. The measurements include: TP-toe pressure measurements (by Periflux
      5000 Laser Doppler and Oxymetry system), SPP-skin perfusion pressure, ABI-ankle
      brachial index, LDP-Laser Doppler baseline and heat perfusion assessment, TcpO2
      without and with O2 provocation inhalation test. In addition, a battery of
      biochemical and hematological tests of peripheral venous blood samples and bone
      marrow analysis were performed. Limb salvage was 81% in 30 patients, 7 patients
      (19%) were amputated for terminal severe ischemia and gangrene progression. In
      the group of limb salvage patients initial Toe pressure 23.119 (std. error 5.358)
      increased in 90 days follow-up into 29.888 (std. error 5.99), Toe brachial index
      increased from 0.1469 (std. 0.0326) to 0.1991(std. 0.401). In LASER doppler and
      TcpO2, TcpCO2 tissue perfusion examination TcpO2% Increase after O2 provocation
      inhalation test was elevated from 162.95 (%) to 229.86% which confirmed a very
      good tissue vasoreactivity after BMSC transplantation.

PMID- 19378842
TI  - [The salvage of ischaemic limb by therapeutical angiogenesis].
AB  - BACKGROUND: Critical limb ischaemia (CLI) is defined as a chronic rest pain,
      lasting more than 2 weeks, requiring analgesics and/or with present skin defects.
      Autologous transplantation of bone marrow mononuclear cells has been used
      successfully in CLI. AIM: The salvage of critically ischaemic limb by endotel
      progenitory cells (EPCs) from patient's bone marrow. To assess efficacy and
      safety of critical lower limb ischaemia treatment with marrow stem cell
      autotransplantation. METHODS: 9 patients suffering from CLI have been enrolled.
      They did not require emergency amputation and had previously been unsuccessfully
      treated with conventional therapy. Mononuclear cells were isolated from the bone
      marrow taken from illiac crest and injected in the gastrocnemius muscle and pedal
      region of the affected limb. Patients have had evaluated: local finding, pain
      index, quality of life index, ABI, fotopletysmography, markers of endothelium and
      trombocytes' activation and digital subtractive angiography. RESULTS: Pain
      severity decreased in all of patients. Three of them are with no pain and no
      claudication. Lesions resolved in two patients, partially in three patients.
      Crural amputation was required in two patients, amputation of leg in 1 patient.
      No side effects of the therapy were observed. One patient died without connection
      with procedure. CONCLUSIONS: Marrow stem cell autotransplantation into the
      ischaemic lower limb seems to be a potentially effective method of peripheral
      perfusion enhancement. Further studies are needed to clarify the underlying
      mechanisms of such improvement.

PMID- 19378843
TI  - [The use of adult human bone marrow stem cells in the treatment of spinal
      injury].
AB  - The spectrum of stem cells therapeutic uses broadens with advancing knowledge
      about this biological material. Treatment of spinal injury is one of the areas of
      stem cell use. Many pre-clinical studies have shown that some cells can, for
      example, transdifferentiate into neuronal cells and replace those that are
      damaged. Through secretion of many growth and neuroprotective factors, stem cells
      prevent, to some extent, progressive cell death, form an environment suitable for
      regeneration of damaged tissue, facilitate neovascularization, remyelinization
      etc., and in consequence may improve post-spinal injury neurological deficit.
      Several clinical studies have been conducted using stem cells in the treatment of
      spinal injury. The present paper provides a brief overview of potential uses of
      stem cells in spinal injury treatment.

PMID- 19378844
TI  - [Our first experiences with autologous transplantation of bone marrow stem cells
      to treat pseudarthrosis, delayed fracture healing and long bone defects
      fracture].
AB  - Traumatology and orthopaedics have undergone substantial progress in the use of
      new, sophisticated techniques, implants and navigation methods. Nevertheless,
      these new methods continue to fail in some instances. Regenerative medicine using
      the growth potential of stem cells that posses the ability to regenerate damaged
      tissues represent one of the possible ways forward. There is a potential for more
      comprehensive utilization of bone marrow stem cells that had for many years been
      used in transplant medicine. Traumatology and orthopaedics could utilise stem
      cells in the treatment of bone defects, i.e. in the treatment of pseudarthrosis,
      delayed fracture healing, defect fractures and aseptic bone necroses. Bone
      formation and growth is a complex, predominantly anabolic, process with a range
      of feedbacks. Nevertheless, it is the bone marrow where the necessary progenitors
      of bone growth are located. These are mesenchymal stem cells (MSCs),
      haematopoietic stem cells (HSCs) as well as thrombocytes containing a range of
      necessary growth factors. A number of studies showed positive results for stem
      cells treatment of pseudarthrosis, with only a fraction, however, being
      statistically significant in human medicine. This method was used in 11 patients
      of the Traumatology Centre of the Faculty Hospital in Ostrava, Czech Republic in
      2008. The researched patients were treated for pseudarthrosis of long bones,
      delayed multifragmentary fracture haling and defect fractures of long bones.
      Autologous concentrate of bone marrow stem cells was applied in one session into
      the area of bone defect in a patient lightly anaesthetised with propofol. The
      results from this small sample of patients are not yet available. However, we are
      sharing our first experiences with this treatment option.

PMID- 19378845
TI  - [Venous thromboembolism prophylaxis in internal medicine].
AB  - Many of medical patients are significant risk of venous thromboembolism (VTE).
      VTE is the most common cause of preventable death in hospitalized patients.
      Prophylaxis is highly effective in reducing the risk of deep vein thrombosis and
      pulmonary embolism and should be used in most hospitalized patients. Various
      strategies improve adherence to evidence-based guidelines on the use of
      prophylaxis, including audit and feedback, and automatic reminders. The important
      clinical risk factors for PE (or venous thromboembolism VTE) include advanced
      age, general anaesthesia, prolonged immobility or paralysis, previous VTE,
      cancer, duration of surgery, orthopaedic surgery of lower limb leg, hip or pelvic
      fracture, major trauma, stroke, obesity, varicose veins, postoperative infection
      and heart failure. Medical patients ad bed rest or who are sick are in moderate
      risk of VTE and evidence based guidelines recommended thromboprophylaxis with low
      molecular weight heparin, or low dose of unfractionated heparin or Fondaparinux.
      For all situations both guidelines recommended against the use of aspirin for VTE
      prevention.

PMID- 19378846
TI  - [Prevention of venous thromboembolism in surgery, laparoscopic surgery and
      urology].
AB  - Deep venous thrombosis and pulmonary embolism are major health problems with
      potential serious outcomes. Acutely, pulmonary embolism may be fatal. In the long
      term, pulmonary hypertension can develop from recurrent pulmonary embolism. Often
      overlooked is post-thrombotic chronic venous insufficiency occurring as a result
      of deep venous thrombosis causing deep venous reflux or obstruction with skin
      changes and ulceration with adverse impact on quality of life and escalation of
      health care costs. Almost all hospitalized patients have at least one risk factor
      for venous thrombosis and approximately 40% have three or more risk factors.
      Without thromboprophylaxis, the incidence of objectively confirmed, hospital
      acquired deep venous thrombosis is approximately 10 to 40% among medical or
      general surgical patients and 40 to 60% following major orthopedic surgery.
      Abundant data from metaanalysis and blinded, randomized clinical trials have
      demonstrated strong evidence that primary thromboprophylaxis reduces deep venous
      thrombosis and pulmonary embolism and little or no increase in the rates of
      clinically important bleeding with prophylactic doses of low-dose unfractionated
      heparin, low-molecular-weight heparin or fondaparinuxem.

PMID- 19378847
TI  - [Venous thromboembolism prophylaxis in orthopaedics and traumatology].
AB  - The paper formulates the following recommendations: 1. Patients with total hip or
      knee replacement should be prescribed higher prophylactic dose of low molecular
      weight heparin (LMWH) or fondaparinux or rivaroxaban or dabigatran, patients with
      proximal femur fracture should be prescribed higher prophylactic dose of LMWH or
      fondaparinux. Pharmacological prophylaxis should in patients with knee
      replacement be administered for at least 14 days and longer in patients with
      increased risk of venous thromboembolism (VTE). It is recommended that the
      prophylaxis lasts 28 to 35 days in patients with hip replacement or with a
      proximal femur fracture. Changeover to warfarin and its subsequent administration
      for 6-8 weeks can be used as an alternative where well-functioning anticoagulant
      treatment infrastructure is available. Intermittent pneumatic compression with
      subsequent pharmacological prophylaxis represents an alternative in bleeding
      patients or in patients with a high risk of bleeding. 2. Pharmacological
      prophylaxis is not needed in patients after knee arthroscopy without VTE risk
      factors in whom tourniquet was applied for < 60 min. Administration of LMWH for 5
      7 days is suitable in patients after knee arthroscopy with VTE risk factors or in
      whom tourniquet was applied for > 60 min., administration of LMWH for 3 weeks is
      recommended in patients after the arthroscopic anteriorcruciate ligament surgery.
      3. Administration of LMWH for 7-10 days is indicated in patients with lower limb
      (LL) fractures treated with osteosynthesis. LMWH administration for the period of
      the fixation is indicated in patients with LL injury requiring plaster cast or
      other fixation above the knee. Administration of LMWH for the period of the
      fixation is indicated in patients with LL injury requiring plaster cast fixation
      below the knee that have increased VTE risk. 4. IPC or leg pump is recommended in
      patients with severe trauma who are bleeding or have a high risk of extensive
      bleeding. Administration of LMWH should be started as soon as the risk of
      extensive bleeding dissipates. Computer tomography (CT) or nuclear magnetic
      resonance imagining (NMRI) should be performed in patients with spinal injury
      with incomplete spinal lesion to exclude perispinal haematoma. Should haematoma
      occur, IPC should be used and CT or NMRI repeated after a few days; it is
      recommended to commence LMWH administration only when the haematoma had been
      stabilized. In case of persisting immobility, continuing LMWH or warfarin
      prophylaxis is recommended.

PMID- 19378848
TI  - [Antithrombotic prophylaxis during pregnancy].
AB  - Coagulation disturbances with their symptoms of thromboembolic--especially venous
      -disease play the most important role in the incidence of maternal mortality. The
      attention is focused on precise diagnostic procedures and on the treatment of all
      the disorders generally accompanied by coagulopathies. First-degree step is
      prevention of above mentioned complications, and the aim of its treatment is
      prevention of longterm complication or consequences. Actually is VTE resolved
      under the condition of the recommendation of 8th ACCP Conference.

PMID- 19378849
TI  - [The profylaxis of venous thromboembolism in gynecology].
AB  - The venous thromboembolism is a serious disease, but it is possible to some
      extend eliminate it by properthromboprophylaxis. The recommendations in
      gynecology result from guidelines not only in surgery and the internal medicine,
      but also from specific gynecologic conditions. The early and frequent
      mobilization is recommended for minor gynecological surgery and laparoscopic
      procedures. For major gynecological surgery and laparoscopic procedures in whom
      additional VTE risk factors are present, low molecular weight heparin is
      indicated. In major gynecological surgery for malignancy, low molecular heparin
      is needed in dose at least 4,000 antiXa IU. The prolonged prophylaxis for 28 days
      is also suitable in this setting.

PMID- 19378850
TI  - [Prophylaxis and treatment of thromboembolism in oncology].
AB  - In this article, following guidelines for clinical practice are formulated. 1.
      For patients undergoing cancer surgery, pharmacological thromboprophylaxis is
      recommended. Low molecular weight heparins (LMWH), unfractionated heparin (UFH)
      5,000 U three times daily, or fondaparinux are recommended; in the Czech
      Republic, LMWH are most frequently used. For patients undergoing major cancer
      surgery extended prophylaxis for 4 weeks is recommended. For patients with a high
      risk of bleeding, intermittent pneumatic compression presents a reasonable
      alternative. 2. For cancer patients, who are bedridden, or hospitalized with an
      acute illness, thromboprophylaxis with LMWH is recommended. Patients with
      multiple myeloma, undergoing induction therapy, including at least 2 thrombogenic
      drugs (thalidomide, lenalidomide, dexamethasone, prednison, and anthracyclines)
      should be treated with LMWH. In other cancer patients, pharmacological
      thromboprophylaxis is not generally recommended, however, its application should
      be considered namely in patients with a history of venous thromboembolism (VTE),
      or in the presence of multiple risk factors. The cancer patients with VTE should
      be treated with LMWH for the first 6 months; the initial dose being 200 IU/kg
      daily, this can be reduced to 2/3-3/4 after one month. The therapy should be
      reevaluated after 6 month and subsequent therapy using LMWH or warfarin is
      recommended indefinitely, unless the cancer is resolved or any major
      contraindications arise.

PMID- 19378851
TI  - Thrombotic complications in children with cancer.
AB  - The last decade has seen advances in treatment of life-threatening disease in
      children--especially cancer where the overall cure rate is now in the region of
      80%. Similar to adults, children with cancer are at a substantial risk of
      developing thromboembolism (TE). One of the costs of achieving this has been more
      children developing thrombotic disease, the majority of which are related to
      indwelling vascular catheters and as a resultTE is being diagnosed with
      increasing frequency in these younger patients. In the Canadian Paediatric
      Thrombophilia Registry, 20% of the patients with TE had cancer. This figure is in
      contrast to only 2.3 cases of malignancy/1000 children and an estimated incidence
      of thrombosis of 0.7/100,000 in the general paediatric population. However, the
      true prevalence of TE in children with cancer is unknown as rates can vary from
      1% to as high as 44% [5] and this reflects the heterogeneity of such studies in
      terms of; (i) type of cancer, (ii) was the TE, symptomatic or asymptomatic and
      (iii) were the studies prospective or retrospective. Happening alongside these
      advances have been an explosion in our knowledge of the understanding at the
      molecular level of blood coagulation in particular how the natural anticoagulant
      and fibrinolytic pathways work and how they differ in children and adults.
      Stemming from these discoveries new anticoagulant therapeutics have become
      available to the paediatrian and over the next decade their true place in the
      treatment of childhood thrombotic disease will be established.

PMID- 19378853
TI  - [Cardiac surgery as a significant interference with a patient coagulation
      status].
AB  - Cardiac surgery has been advancing intensively in recent years. However, it is
      often forgotten that cardiac surgery interventions represent a significant
      interference with patient's coagulation status. This paper summarizes the main
      processes in the course cardiac surgery that lead to coagulation disorder. These
      include: * haemodilution resulting from extracorporeal circuits crystalloid
      priming and the use of cardioplegic solutions leading to the reduction in
      coagulation factors concentration and the thrombocytes count * full
      heparinisation during extracorporeal circulation that represents a significant
      interference with coagulation that may persist for some time even after all
      heparin has been bound * contact of the blood with inorganic surface that results
      in an activation of the coagulation cascade and subsequent consumption of
      coagulation factors and thrombocytes * surgery-related trauma with activation of
      the external coagulation pathway leading to activation of the coagulation cascade
      and subsequent consumption of coagulation factors and thrombocytes * blood re
      transfusion from the pericardial cavity and subsequent activation of the external
      coagulation pathway leading to consumption of coagulation factors and
      thrombocytes * hypothermia leading to thrombocyte dysfunction and initiation of
      fibrinolysis * blood loss furthering the haemodilution and reduction in
      coagulation factors concentration and thrombocytes count. The overview provided
      suggests that cardiac surgery conducted with the support of extracorporeal
      circuit represents a significant interference with the coagulation status of the
      patient. Awareness of the above listed changes is necessary to secure correct
      post-operative management of coagulation disorders.

PMID- 19378852
TI  - Treatment of deep vein thrombosis with continuous intravenous infusion of LMWH in
      children--an alternative to subcutaneous application when needed.
AB  - Incidence of thrombosis is age dependent with the lowest risk in the childhood.
      Children mostly suffer from vein thrombosis. Incidence of thrombosis in children
      is only 0.07/10,000, but it increases among hospitalized children (3.5/10,000).
      Subcutaneous administration of low molecular weight heparin (LMWH) is preferred
      treatment of deep vein thrombosis in children. In this study we present group of
      33 children with deep vein thrombosis, who were treated with LMWH for their first
      thrombosis from 2003 till 2006. Twenty-one (63.6%) patients were treated with
      LMWH by continuous infusion and 12 (36.3%) patients by subcutaneous injection.
      Duration of the treatment with LMWH was modified in accordance with the course of
      thrombosis (monitored by Doppler ultrasound with compression) with median of 15
      days in patients treated by continuous infusion and 18.5 days when treated
      subcutaneously. Median dose of LMWH for intravenous and subcutaneous application
      was 240 IU/kg/24 h and 215 IU/kg/24 h respectively. The administered dose of LMWH
      was modified to achieve and maintain required therapeutic antiXa level within the
      range of 0.5-1 IU/ml. The treatment with continuous infusion led to total
      recanalisation of the occluded vein in 3 cases (14.3%), partial recanalisation
      was achieved in 15 (71.4%) patients. Three (14.3%) patients were without any
      recanalisation. The treatment by subcutaneous injection led to total
      recanalisation of the vein in 4 cases (33.3%), partial recanalisation was seen in
      4 (33.3%) patients. Four (33.3%) patients were without any recanalisation. The
      difference in the outcomes of the therapy between both groups appears to be
      statistically significant (p = 0.041, nonparametric Mann-Whitney test). We have
      not noticed any severe adverse event of the treatment in any of our patients. Our
      results support the hypothesis that the treatment of DVT with continuous infusion
      of LMWH might be efficient and safe alternative to subcutaneous application in
      those children in whom we want to avoid subcutaneous administration from certain
      reasons.

PMID- 19378854
TI  - [Pre-operative care for cardiac surgery patients with cold antibody disorder,
      cryoglobulinaemia and cryofibrinogenemia].
AB  - We present an example of a patient with confirmed cold agglutinin disease who
      underwent cardiac surgery in hypothermia to illustrate a known fact that, when
      exposed to cold, cold agglutinins induce haemolysis of erythrocytes and that
      cryoglobulins and cryofibrinogens may, upon exposition to cold during a surgery
      under hypothermia, precipitate or gelify and thus increase plasma viscosity and
      damage microcirculation. Detailed immunological and haematological investigations
      in all patients awaiting cardiac surgery with a risk of developing hypothermia is
      not advantageous considering the low number of patients with clinical and
      laboratory signs of cold agglutinin disease, autoimmune haemolytic anaemia or
      paroxysmal cold haemoglobinuria and considering that these investigations, in
      addition, might not detect cryoglobulinaemia and cryofibrinogenemia.
      Identification of in-risk patients from the warning signs in the medical history,
      physical or basal laboratory testing who would subsequently undergo confirmatory
      investigations to verify the presence of these entities and define them
      accurately might be a potential solution to this clinical issue. Cardiac surgery
      strategy and peri-operative care should be tailored to the results of these
      investigations. Well-structured, practiced and functional cooperation between
      clinicians and laboratory personnel is a prerequisite for success in these
      circumstances.

PMID- 19378855
TI  - [Thrombophilic states: their relevance in prevention and treatment of venous
      thromboembolism].
AB  - Thrombophilic states are congenital or acquired haemostasis disorders with
      pathophysiological and statistical association to increased risk of thrombosis.
      Venous thromboembolism is their most important clinical manifestation. More than
      50% of patients with unprovoked thrombosis have one of the known thrombophilias.
      Patients with congenital thrombophilias have, in comparison to those without
      thrombophilia, increased risk of the first thromboembolic event, while the impact
      of genetically defined thrombophilic states on recurrence is less evident. The
      risk of recurrence in patients with idiopathic thrombosis is 7-10% per year even
      in the absence of a known thrombophilia. The risk of recurrent event is affected
      by a range of other factors (persisting or undiagnosed precipitating factor,
      proximal thrombosis and pulmonary embolism, incomplete recanalization, vessel
      thrombosis, presence of some thrombophilias, high D-dimmer levels after
      anticoagulant therapy discontinuation). Identification and subsequent monitoring
      of these factors is crucial for optimal selection of the treatment to be used as
      a secondary prevention of venous thromboembolism and its duration. Primary
      prevention of venous thromboembolism requires good knowledge of general
      precipitating factors as well as the specific risks in each patient and thus also
      means an early investigation of thrombophilic states in patients who will benefit
      from their identification and in whom there is at least medium probability of
      their identification. Universal long-term prevention in so far asymptomatic
      carriers of congenital thrombophilias is not indicated considering the potential
      complications of anticoagulant treatment. Women with thrombophilic disorders have
      an increased risk of thromboembolic event if using hormonal contraception and
      during pregnancy. They also have an increased risk of pregnancy complications
      related to placental circulation blood flow disorders.

PMID- 19378856
TI  - [Antiphospholipid syndrome in the year 2009].
AB  - Antiphospholipid syndrome is a prothrombotic disorder characterized by vascular
      occlusions and/or pregnancy morbidity in the presence of antiphospholipid
      antibodies. These autoantibodies represent a large and heterogenous family of
      circulating immunoglobulins usually identified as anticardiolipin antibodies and
      antibodies directed against beta2-glykoprotein I or as lupus anticoagulant. A
      number of criteria for diagnosis of antiphospholipid syndrome have been proposed.
      In this review, we focused on long-term process of diagnostic procedures
      development and future directions in scientific research in this field.

PMID- 19378857
TI  - [Blood platelets metabolic and activation processes and options for their
      inhibition].
AB  - A range of activation processes and confirmatory and metabolic changes take place
      in blood platelets following their activation. The paper discusses some of the
      blood platelet activation steps and describes the specific processes that take
      place on this level. Furthermore, the points at which it is possible to actively
      interfere with the blood platelet metabolism or activation processes are
      described. Antiplatelet treatment focuses on these points and there are efforts
      to identify active substances that either inhibit access to certain receptors or
      targets or, alternatively, inhibit the enzymes participating in these processes.

PMID- 19378858
TI  - [Inferior vena cava filters in pulmonary embolism prevention].
AB  - Pulmonary embolism (PE) is the most serious sign of venous thromboembolism and
      the 3rd most frequent cause of cardiovascular death. Therapy with anticoagulants
      represents, among other measures, the mainstay of PE treatment. However,
      anticoagulant therapy does not prevent recurrence of pulmonary embolism in 3-20%
      of patients. Most frequently, the source of pulmonary embolism is in venous
      circulation of lower limbs and pelvis. Interception of the inferior vena cava,
      originally surgical, later using inferior vena cava filters, is used as a
      preventive measure. Indications and contraindications of inferior vena cava
      filters have been redressed and modified several times; the paper provides their
      list. Older filters used to be retained within the inferior vena cava (so called
      permanent filters). This was one of the causes of relatively high incidence of
      complications related to the use of these filters, particularly venous
      thromboses, as confirmed by so far the only randomised study PREPIC.
      Consequently, retrievable filters that are currently preferred have been
      developed. The authors also provide an overview of studies in progress, describe
      the process of implantation and describe own patient group.

PMID- 19378859
TI  - [Preparation of patients on anticoagulant treatment for invasive surgery].
AB  - The management of warfarin therapy in patients undergoing surgery or other
      invasive procedures involves a balance between the risk of hemorrhage, and the
      risk of thrombosis. Risk of hemorrhage and the trombosis depends on the type of
      procedure and on pre-existing conditions. Procedures with low risk of hemorrhage
      (dental, dermatologic or ophtalmologic procedures, endoscopy) can be provided
      with continuing anticoagulant therapy. Surgery with high hemorrhagic risk need
      stop warfarin and start bridging anticoagulant therapy, such as unfractionated
      heparin or low molecular weight heparin, prior and after surgery. In patients
      requiring emergency surgery, vitamin K, prothrombin complex concentrate or fresh
      frozen plasma can be used to improve coagulation.

PMID- 19378861
TI  - [Laboratory procedures following thrombocytopenia diagnosis].
AB  - Thrombocytopenia--decrease in the blood platelets count below 100 x 10(9)/L--may
      represent a significant clinical complication--bleeding. A risk of haemorrhagic
      complications increases with the severity of thrombocytopenia. Even severe
      thrombocytopenia, however, may be a sign of a condition with predominant symptoms
      of thrombosis where bleeding is on the background (thrombotic microangiopathy,
      for example) or where bleeding occurs concurrently with symptoms of thrombosis
      (so called thrombohaemorrhagic syndromes). It is necessary to exclude
      pseudothrombocytopenia when thrombocytopenia is first diagnosed. It is then
      recommended to follow a standardized differential diagnosis algorithm that should
      be available at each clinical site. We summarize the general rules of
      thrombocytopenia differential diagnosis with a specific focus on laboratory
      processes.

PMID- 19378860
TI  - [Bleeding complications of anticoagulant therapy].
AB  - Anticoagulant therapy is one of the most common forms of medical intervention. It
      is the mainstay of prevention and treatment of thrombotic events. Omission of
      adequate anticoagulant prophylaxis at least for moderate-risk and high-risk
      patients is a widely recognized medical error. Bleeding is one of the most feared
      complications of anticoagulant therapy, and is a risk of all anticoagulants.
      Whereas unfractionated heparin and warfarin, the oldest and most widely used
      anticoagulants, have specific antidotes for their anticoagulant effect, many of
      the newer agents (direct and indirect inhibitors of coagulation factors Xa and/or
      IIa) do not have specific antidotes to reverse their actions. The use of novel
      anticoagulants is further complicated by a lack of easily available laboratory
      tests to measure their levels and thereby optimize their benefit and safety in
      clinical practice. In this review, we evaluate the risk of bleeding associated
      with current anticoagulants, review the data available on current and
      experimental agents used for the reversal of anticoagulation, and provide
      recommendations for the management of major bleeding associated with
      anticoagulant therapy and for the management of asymptomatic overdosing of the
      anticoagulants.

PMID- 19378862
TI  - [Advances in antithrombotic treatment--antithrombotics with anti-Xa effect].
AB  - The use of anticoagulants in the prophylaxis and treatment of arterial and venous
      thrombosis has substantially expanded during the last years. Increasing knowledge
      about the inherited and acquired thrombophilia and the risk factors predisposing
      to the recurrency of thromboembolic events result in a new indications for
      primary and secondary thromboprophylaxis with prolonged or even life-long
      duration. The limitations of classical anticoagulans, heparin and vitamin K
      antagonists support the development of medicaments with a specific antithrombotic
      action. The new generation anticoagulants inhibit in a specific way either
      particular coagulation enzyme or hemostasis activation step. Based on the in
      vitro studies and extensive clinical observations the activated factor Xa (FXa)
      seems to be one of the most advantageous targets for a specific action of
      perspective antithrombotic agents. Two selective F Xa inhibitors have been
      approved for clinical use: fondaparinux is an indirect parenteral F Xa inhibitor,
      and most recently approved rivaroxaban is the first oral anti-Xa inhibitor. Other
      anti-Xa molecules are under development for either parenteral (idraparinux, DX
      9065a) or oral use (razaxaban, apixaban, rivaroxaban, LY-51, 7717, BMS-56247 a DU
      176b).

PMID- 19378863
TI  - [Molecular methods in thrombophilic states diagnostics].
AB  - Molecular genetic methods passed into the field of investigation of thrombophilic
      states in 90th years of last century, along with the first discoveries of
      coagulation inhibitors (AT III, protein C and protein S). They have acquired a
      widespread use above all with the detection of the molecular basis of activated
      protein C (APC) resistance in 1994 by prof. Bertina. At the present time, a wide
      range of molecular genetic markers, linked with a clearly documented increased
      risk of thrombophilia are adapted. They include mutations of factor V Leiden
      506R/Q, of protrombin 20210G/A, MTHFR 677C/T in homozygous form, mutation of PAI
      1 4G/5G, mutations of different coagulation inhibitors and finally a range of
      polymorphisms with still not precisely defined increased risk for thrombophilia
      (F XIII Val34leu, platelets glycopeproteins, endothelial protein C receptor and
      trombomodulin). From the methodological viewpoint, all these techniques are based
      on the principle polymerase chain reaction (PCR). In the last period of time,
      however there was a rapid evolution, allowing a significant improvement in their
      laboriousness. Nowadays, splitting with the aid of restriction endonucleases,
      real time PCR or allel specific primers for PCR. The second, where molecular
      genetic methods are currently under use, is pathophysiological investigation of
      the single coagulation processes. Here, in a fact, most significant progress has
      been in the field of APC resistance made elucidation. Although still in the 90th
      years of the past century the genetical cause of these coagulation disturbance
      was unequivocally documented its clinically heterozygous appears not yet fully
      understood at the moment. Similarly, in prothrombin mutation, only the latest
      investigations have outlined the probable mechanism of expression. Concerning the
      future evolution of molecular genetic methods, there can be observed a clear cut
      tendency to better understanding the pathophysiologic cause of thrombophilia in
      comparison with the searching for new coagulation defects which consecutively
      bear lesser a relative risk of thrombosis.

PMID- 19378864
TI  - [First angiologic facility--35th anniversary of the founding of the first
      clinical angiologic facility in the Slovak Republic].

PMID- 19378865
TI  - [Savants and cultutal boundaries. Thermalism in Savoy and the work of Joseph
      Daquin (1732-1815)].
AB  - The essay sets out to explain the general orientation of the studies, the
      problems, the perspectives and the research that were done by Joseph Daquin (1732
      1815), a physician born in Chambery (Savoy, Kingdom of Sardinia). He had a
      secular education at the Faculty of Medicine of Turin, where he earned his degree
      under Ignazio Somis and Vitaliano Donati. The aim of this essay is to give a
      critical contribution to cultural history and examine the origins of thermalism
      with particular emphasis on therapy, physics experiments, and its relation to
      political and social structure. Daquin was a witness of the advancement of
      science beyond the boundaries of scientific Enlightenment. His overriding
      intellectual concern was with the meaning and impact of chemistry theories on
      medical practices. The author has published an interesting Analyse des eaux
      thermales d'Aix en Savoie (1773), a natural experimental history of mineral
      waters in Aix-les-Bains.

PMID- 19378866
TI  - [Making offspring from act and substance. Experimenting with procreation and
      paternity in reproductive medicine and fiction].
AB  - As an experimental medical practice artificial insemination in humans dates back
      to the end of the 18th century. Efforts intensified in the second half of the
      19th century, when, especially in France, the number of reports in scientific
      publications increased and the topic became the subject of heated debates. I
      trace this emergence of reproductive medicine avant la lettre by reviewing the
      relevant medical publications. Hereby, I focus on how experiments in artificial
      insemination presupposed a new conceptualisation of procreation which detaches
      procreation from the doings of human actors by reducing it to the fusion of germ
      cells. This "biologisation" of procreation entailed a series of irritations with
      regard to the determination of "natural" paternity and the impact and relevance
      of the procreative act's nature. These irritations are dealt with in a novel that
      appears in Paris in 1884, entitled The Man-Maker. This novel thus attests to the
      cultural uncertainties that went along with the emergence of what laid the
      epistemological ground for the reproductive medicine to come.

PMID- 19378867
TI  - [Tarentism and its ethnographic fictions: the epistemology of the other's
      disease].
AB  - Tarantism is a cultural syndrome caused by a symbolic spider bite that was
      treated in Southern Italy by means of a musical and religious ritual. At the
      frontiers of theories of insanity this "disease" is the source of a rich and
      centuries-old scientific literature. This article proposes an epistemological
      analysis of the medical paradigms that have built the scientific representations
      of this phenomenon and that make it an anthropological mediation of cultural
      alterity of the Apulian territory and Southern Italy in general. Geographical or
      social determinism, popular irrationality, simulation and imitation appear as
      recurrent categories sounding the psychology of a "meridional soul" explained,
      till the studies of the 20th century about the south-European immigrants'
      diseases, in terms such as social anomy and mental alienation.

PMID- 19378868
TI  - [Research on surgeries (1500-1900)].

PMID- 19378869
TI  - Long-term benefits of a vegetarian diet.

PMID- 19378870
TI  - Listening for signals.

PMID- 19378871
TI  - Heparins for unstable angina and non-ST segment elevation myocardial infarction.

PMID- 19378872
TI  - Aerobic activity for cognitive function.

PMID- 19378873
TI  - Infant formula.
AB  - Although the American Academy of Pediatrics and the American Academy of Family
      Physicians recommend breast milk for optimal infant nutrition, many parents still
      choose formula as an acceptable alternative. The wide variety of available
      formulas is confusing to parents and physicians, but formulas can be classified
      according to three basic criteria: caloric density, carbohydrate source, and
      protein composition. Most infants require a term formula with iron. There is
      insufficient evidence to recommend supplementation with docosahexaenoic acid or
      arachidonic acid. Soy formulas are indicated for congenital lactase deficiency
      and galactosemia, but are not recommended for colic because of insufficient
      evidence of benefit. Hypoallergenic formulas with extensively hydrolyzed protein
      are effective for the treatment of milk protein allergy and the prevention of
      atopic disease in high-risk infants. Antireflux formulas decrease emesis and
      regurgitation, but have not been shown to affect growth or development. Most
      infants with reflux require no treatment. Family physicians can use these
      guidelines to counsel parents about infant formula, countering consumer
      advertising that is not evidence-based.

PMID- 19378874
TI  - Diets for cardiovascular disease prevention: what is the evidence?
AB  - Patients often initiate commercial dietary plans to reduce obesity and prevent
      cardiovascular disease. Such plans include very low-carbohydrate, low
      carbohydrate, very low-fat, and Mediterranean diets. Published evidence on
      several popular diets has made it easier for physicians to counsel patients about
      the health benefits and risks of such plans. Although the Atkins, Zone, Sugar
      Busters!, and South Beach diets have data proving that they are effective for
      weight loss and do not increase deleterious disease-oriented outcomes, they have
      little evidence of patient-oriented benefits. In contrast, the Mediterranean diet
      has extensive patient-oriented outcome data showing a significant risk reduction
      in mortality rates and in rates of fatal and nonfatal myocardial infarction. The
      American Heart Association released guidelines in 2006 that integrate
      recommendations from a variety of diets into a single plan. Physicians should
      emphasize diets that are rich in fruits, vegetables, and healthful fatty acids
      and that limit saturated fat intake. A stepwise individualized patient approach,
      with incorporation of one or two dietary interventions every three to six months,
      may be a practical way to help reduce a patient's cardiovascular disease risk.

PMID- 19378875
TI  - Epididymitis and orchitis: an overview.
AB  - Epididymitis and orchitis are commonly seen in the outpatient setting. Men
      between 14 and 35 years of age are most often affected, and Chlamydia trachomatis
      and Neisseria gonorrhoeae are the most common pathogens in this age group. In
      other age groups, coliform bacteria are the primary pathogens. Men with
      epididymitis and orchitis typically present with a gradual onset of scrotal pain
      and symptoms of lower urinary tract infection, including fever. This presentation
      helps differentiate epididymitis and orchitis from testicular torsion, which is a
      surgical emergency. Typical physical findings include a swollen, tender
      epididymis or testis located in the normal anatomic position with an intact
      ipsilateral cremasteric reflex. Laboratory studies, including urethral Gram
      stain, urinalysis and culture, and polymerase chain reaction assay for C.
      trachomatis and N. gonorrhoeae, help guide therapy. Initial outpatient therapy is
      empirical and targets the most common pathogens. When C. trachomatis and N.
      gonorrhoeae are suspected, ceftriaxone and doxycycline are recommended. When
      coliform bacteria are suspected, ofloxacin or levofloxacin is recommended.

PMID- 19378876
TI  - Green tea: potential health benefits.
AB  - Green tea has been used widely and in high doses for centuries as a health tonic
      in many societies. Evidence suggests that green tea is effective for treating
      genital warts. There is some supportive evidence for the use of green tea in
      cancer prevention. Drinking green tea is associated with a decrease in all-cause
      mortality, but not in cancer-related mortality. Small clinical studies have found
      that green tea may also be helpful in losing and managing weight, and lowering
      cholesterol. Epidemiologic evidence suggests that green tea may prevent stroke
      and cardiovascular disease. Green tea appears to be safe, although there have
      been case reports of hepatotoxicity possibly related to a specific extract in
      pill or beverage form. Green tea seems to be a low-risk complementary therapy for
      a number of conditions, but more studies are needed.

PMID- 19378877
TI  - Chronic neck pain. Diffuse idiopathic skeletal hyperostosis.

PMID- 19378878
TI  - Tactile spatial working memory activates the dorsal extrastriate cortical pathway
      in congenitally blind individuals.
AB  - In sighted individuals, both the visual and tactile version of the same spatial
      working memory task elicited neural responses in the dorsal "where" cortical
      pathway (Ricciardi et al., 2006). Whether the neural response during the tactile
      working memory task is due to visually-based spatial imagery or rather reflects a
      more abstract, supramodal organization of the dorsal cortical pathway remains to
      be determined. To understand the role of visual experience on the functional
      organization of the dorsal cortical stream, using functional magnetic resonance
      imaging (fMRI) here we examined brain response in four individuals with
      congenital or early blindness and no visual recollection, while they performed
      the same tactile spatial working memory task, a one-back recognition of 2D and 3D
      matrices. The blind subjects showed a significant activation in bilateral
      posterior parietal cortex, dorsolateral and inferior prefrontal areas, precuneus,
      lateral occipital cortex, and cerebellum. Thus, dorsal occipito-parietal areas
      are involved in mental imagery dealing with spatial components in subjects
      without prior visual experience and in response to a non-visual task. These data
      indicate that recruitment of the dorsal cortical pathway in response to the
      tactile spatial working memory task is not mediated by visually-based imagery and
      that visual experience is not a prerequisite for the development of a more
      abstract functional organization of the dorsal stream. These findings, along with
      previous data indicating a similar supramodal functional organization within the
      ventral cortical pathway and the motion processing brain regions, may contribute
      to explain how individuals who are born deprived of sight are able to interact
      effectively with the surrounding world.

PMID- 19378880
TI  - The role of cholinergic system in neuronal plasticity: focus on visual cortex and
      muscarinic receptors.

PMID- 19378879
TI  - Psychophysiological aspects of voluntary skilled movement after stroke: a follow
      up study.
AB  - OBJECTIVES: The aim of the study was to follow the psychophysiological evolution
      of a self-paced voluntary skilled movement in hemiparetic subjects after ischemic
      stroke by means of a skilled performance task (SPT). The task consisted in
      starting a sweep of an oscilloscope trace by pushing one button with the left
      index finger (trigger point), and in stopping it within a central area on the
      oscilloscope screen, between 40 and 60 ms (correct performance) after the start
      of the sweep, by pushing the other button with the right index finger. A SPT
      yields a considerable amount of information on the electrophysiological
      components, which reflect pre-programming activity (Bereitschaftspotential--BP),
      control strategies (Skilled Performance Positivity--SPP) and behavioural response
      (Correct Performances). The study was also aimed at detecting any longitudinal
      changes in the psychophysiological pattern, as evaluated by the clinical
      examination and specific motility scales, that parallel motor recovery. METHODS:
      Movement related potentials (MRPs) were recorded in 12 control subjects and 9
      patients in the acute phase, before the start of neurorehabilitation (time 0),
      when the patients were able to execute an index finger press with the affected
      hand. The patients (mean age = 62.33 years, SD = 8.17) presented a mild to
      moderate central arm paresis caused by a first-ever unilateral supratentorial and
      subcortical ischemic lesion. The subsequent recordings were carried out
      respectively 3, 9 and 12 months later. RESULTS: At the first recording,
      hemiparetic patients achieved a significantly lower percentage of correct
      performances and had a lower BP amplitude than controls (p < 0.001); SPP was
      absent. The number of correct performances did not improve significantly during
      the subsequent recordings. BP amplitude showed a mild increase in the second,
      third and fourth recordings (p < 0.05), while SPP amplitude revealed a slight
      improvement at the second and a marked improvement at the third and fourth
      recordings, when there was no longer a statistically significant difference from
      controls. CONCLUSIONS: Our findings point to an early recovery of pre-programming
      activity and a delayed improvement in control activity. The delayed development
      of control activity in the absence of procedural learning, i.e. skill learning
      through practice, forces patients to exploit attentional strategies to compensate
      for their procedural learning impairment. SPT shows that the efficacy of physical
      therapy aimed at motor ability recovery in hemiparetic patients does not keep up
      with the slow recovery process of an automatic motor level.

PMID- 19378881
TI  - Brain representation of phonological processing in Italian: individual
      variability and behavioural correlates.
AB  - Neuroimaging literature on phonological processing during reading lacks of
      studies taking into account orthographic differences across languages and
      behavioural variability across subjects. The present study aimed at investigating
      brain representation of phonological processing in reading Italian, a language
      with regular orthography, with particular regard to inter-individual variability
      and brain-behavioural correlates. Ten Italian adults performed a rhyme generation
      and a rhyme judgment task during fMRI acquisition and were tested with
      behavioural measures of phonological processing. Results for both tasks showed
      activations of the left Inferior Frontal Gyrus and Dorsolateral Prefrontal
      Cortex, likely underlying output sublexical strategies, for all or most of the
      subjects, while a minority of subjects activated the Superior Temporal Sulcus and
      the Temporo-Parietal-Occipital Junction. These results suggest that phonological
      processing of written Italian is based on the prevalent use of frontal
      structures. However, it is of interest that the activation of the Superior
      Temporal Sulcus, involved in phonological input, was associated to better
      behavioural performances in tasks of phonological processing. Our findings may
      contribute to understand neural correlates of phonological processing of
      languages with regular orthography.

PMID- 19378882
TI  - Ribosomal RNA characterization in the leech Hirudo medicinalis.
AB  - In the present study the ribosomal RNA of the leech Hirudo medicinalis has been
      characterized at the aim of identifying possible analogies with other
      invertebrates. Upon electrophoresis on denaturating gels, ribosomal RNA fraction
      of H. medicinalis exhibited a remarkable thermal instability by dissociating into
      two hydrogen-bonded components when heated at 60 degrees C, at variance with the
      behaviour of the rat rRNA, which does not show this process. This result suggests
      a functional role in leech ribosome organisation that requires deeper structural
      studies.

PMID- 19378883
TI  - Visceral childhood leishmaniasis in southern Turkey: experience of twenty years.
AB  - One hundred and one children with visceral leishmaniasis (VL) who admitted to
      Akdeniz University Hospital during a 20-year period were analyzed. Median age of
      the patients was 3 years (range: 5.5 months-13 years). The most common symptoms
      at presentation were fever, pallor and abdominal distension. Splenomegaly was
      found in all of the patients while hepatomegaly was present in 98%. Anemia (96%),
      leukopenia (74%) and thrombocytopenia (56%) were the main laboratory
      abnormalities. Thirty-three (33%) of the patients were pancytopenic on admission.
      Bone marrow smear was positive for leishmania in 91% of the patients. Seventy
      four patients were treated with antimony +/- pentamidine and 27 with amphotericin
      B. Three of our patients died because of secondary infections and hemorrhage.
      Relapse was observed in two patients. No patient showed post kala-azar dermal
      leishmaniasis findings. We conclude that VL should be considered in patients with
      prolonged fever, hepatosplenomegaly and cytopenia who live in an endemic region.
      Amphotericin B is a therapeutic agent as effective as pentavalent antimony
      compounds and could be preferred.

PMID- 19378884
TI  - Reference values for urinary calcium, sodium and potassium in healthy newborns,
      infants and children.
AB  - The urinary calcium/creatinine ratio (UCa/Cr) in spot urine samples has been used
      extensively for screening and diagnosis of hypercalciuria (HC). The aim of this
      study was to determine the normal values for UCa/Cr, urinary sodium/creatinine
      (UNa/Cr), urinary potassium/creatinine (UK/Cr) and urinary sodium/potassium
      (UNa/K) ratios in healthy Turkish children aged 0-5 years. A total of 425
      children were enrolled in the study. The urine samples were obtained from the
      second morning urine in children after breakfast and the first urine after
      feeding in infants. Urine Ca, Cr, Na and K levels were studied. A positive
      correlation was found between the UCa/Cr, UNa/Cr, UK/Cr and UNa/K ratios. Our
      results suggest that UCa/Cr is age-related and declines in the first five years
      of life except for in the newborn period. It might be concluded that
      determination of the upper limit of UCa/Cr in children less than five years old
      for every population can prevent unnecessary laboratory investigations and
      misdiagnosis of hypercalciuria.

PMID- 19378885
TI  - The effect of kangaroo care on pain in premature infants during invasive
      procedures.
AB  - A total of 50 premature infants (25 in KC group, 25 in control group) were
      included in this comparative, randomized, controlled study. Gestational and
      postnatal ages of the infants were between 26-36 weeks and 0-28 days,
      respectively. Infants with congenital abnormalities or sepsis and those who
      needed mechanical ventilation or surgical intervention were not included in the
      study. None of the infants received narcotic analgesics. Behavioral and
      physiologic responses to pain were recorded and Premature Infant Pain Profile
      (PIPP) was used to evaluate the severity of pain. Collected data was evaluated
      using SPSS for Windows 11.5 program. Premature Infant Pain Profile scores were
      significantly lower at each measurement during or soon after the invasive
      procedure in infants in the KC group compared to controls. In conclusion, KC
      starting 30 minutes before and continuing 10 minutes after an invasive procedure
      was found to be effective in decreasing pain during and after the invasive
      procedure in premature infants.

PMID- 19378886
TI  - Pediatricians' knowledge about recent advances in anaphylaxis treatment in
      Istanbul, Turkey.
AB  - Severe anaphylactic reactions are medical emergencies in children and require
      immediate recognition and treatment. Many advances have been reported recently in
      the treatment of anaphylaxis. Despite this, little is known about whether or not
      these advances are known by all pediatricians. To evaluate the knowledge of
      pediatricians on the recent advances in the treatment of anaphylaxis, some
      pediatricians from istanbul were asked to complete an anonymous questionnaire. A
      total of 124 pediatricians agreed to participate in the study. Most attendants
      (92%) knew epinephrine as the first drug in the treatment of anaphylaxis, but
      more pediatricians (65%) also preferred subcutaneous route as the most effective
      route for injection. In addition, more than 80% did not know the trademarks of
      epinephrine autoinjectors or the amount of the drug in the autoinjectors. Our
      data show that the level of pediatricians' knowledge about recent advances in the
      management of anaphylaxis is unsatisfactory. Pediatricians' failure to know
      recent advances in the management of anaphylaxis may endanger children when
      assistance is required. Educational programs aimed at improving the general
      knowledge of pediatricians on recent advances in anaphylaxis are urgently needed.

PMID- 19378887
TI  - Carvedilol therapy in pediatric patients with dilated cardiomyopathy.
AB  - Carvedilol reduces mortality and hospitalization in adults with congestive heart
      failure. Limited information is available about its use in children. The
      objective of this study was to determine the dosing, efficacy and side effects of
      carvedilol for the management of dilated cardiomyopathy in children. Sixteen
      children with idiopathic dilated cardiomyopathy, aged 7 months to 138 months and
      with an ejection fraction less than 40%, were treated with carvedilol. The
      average initial dose was 0.1 mg/kg/day and it was uptitrated to 0.4 mg/kg/day.
      After six months on carvedilol, there were improvements in clinical scoring
      system from an average of 2.94 to 2.50 (p<0.05), in mean fractional shortening
      from 17.2 +/- 6.1% to 22.7 +/- 5.1% (p<0.05), and in ejection fraction from 35.2
      +/- 6.8% to 43.1 +/- 11.2% (p<0.05). No side effect was observed during the study
      period. Two patients died due to serious infection. Carvedilol in addition to
      standard therapy for dilated cardiomyopathy in children improves cardiac function
      and symptoms. It is well tolerated, with minimal adverse effects, but close
      monitoring is necessary.

PMID- 19378888
TI  - Characterization of extended-spectrum beta-lactamase-producing Salmonella
      isolates in a children's hospital in Ankara--first report of SHV-2a and SHV-9 in
      Salmonella spp. from Turkey.
AB  - The rate of in vitro resistance to various antimicrobials in 179 consecutive
      isolates of Salmonella spp., which included serogroups D (109), B (52), C1 (10)
      and C2 (8) isolated from children, was investigated. Production of extended
      spectrum beta-lactamase (ESBL) was studied in ampicillin-resistant isolates.
      Antimicrobial susceptibilities were determined by disk diffusion tests and by
      BIOMIC video reader system. Overall resistance rates to ampicillin and
      amoxicillin/clavulanate were 26.3% and 10.6%, respectively. Resistance to
      ceftriaxone and ceftazidime was 3.3%. Resistance rates for chloramphenicol,
      trimethoprim-sulfamethoxazole, ciprofloxacin, amikacin and gentamicin were 40.7%,
      31.3%, 2.2%, 2.2% and 6.1%, respectively. beta-lactamase production was detected
      in 42 isolates. Mating out experiments, isoelectric focusing, dot blot
      hybridization, polymerase chain reaction (PCR) and sequencing were performed on
      two S. paratyphi B isolates that produced ESBLs. One isolate produced SHV-2 and
      TEM-1 and the other produced SHV-2a, SHV-5a (SHV-9) and TEM-1. This is the first
      report of SHV-2a and SHV-5a (SHV-9) in S. paratyphi B in Turkey.

PMID- 19378889
TI  - Effect of pacifier use on exclusive and any breastfeeding: a meta-analysis.
AB  - The objective of this meta-analysis was to determine with cross-sectional and
      cohort trails whether the use of pacifier increases the risk of early weaning
      from exclusive breastfeeding before six months of age or cessation of
      breastfeeding from any breastfeeding before 24 months of age. Additionally, the
      effect of the age for starting pacifier use on breastfeeding duration was
      analyzed in the cohort trails. The Medline database was searched (1980 to 2006)
      with "breastfeed, breastfeeding, or breast feed" and "pacifier, dummy, or
      soother" as individual keywords. Only human studies published in English were
      included. Unpublished data were not sought. Twelve trials with weaning from
      exclusive breastfeeding and 19 trials with cessation of any breastfeeding were
      included in the meta-analysis. The meta-analysis was performed with Stata 6.0
      statistical package. Summary risk ratio for early weaning before six months of
      age in exclusive breastfeeding trails was 2.016 (95% CI: 1.619-2.511) for
      pacifier users compared with nonusers in studies with univariate analysis and
      1.792 (95% CI: 1.452-2.212) in studies with multivariate analysis. Similarly,
      pacifier usage compared with nonusers reduced the duration of any breastfeeding
      in both univariate (2.760, 95% CI: 2.083-3.657) and multivariate trials (1.952,
      95% CI: 1.662-2.293). The use of pacifiers was associated with shortened duration
      of exclusive and of any breastfeeding. Given the increase in the benefits with
      duration of breastfeeding, parents should be informed of the link between
      pacifier use and shortened breastfeeding duration in order to help them make
      informed decisions about their children's care.

PMID- 19378890
TI  - Pilomatricoma: a review of six pediatric cases with nine lesions.
AB  - Pilomatricoma, although rare, is the second most frequent benign skin tumor in
      childhood. It is a hard, painless, slowly progressing subcutaneous tumor that is
      commonly located in the head-neck region, especially periorbital, and in the
      upper extremities. Histopathologic characteristics are distinctive. In this
      study, we performed a retrospective review of the records of our pediatric
      patients with pilomatricoma. We discuss herein the diagnosis and management of
      this uncommon skin tumor, and compare our experience with the previous
      literature. Pilomatricoma should be included in the differential diagnosis of
      superficial pediatric head and neck masses by any physician involved with
      pediatric tumors.

PMID- 19378891
TI  - Factors affecting onset of puberty in Denizli province in Turkey.
AB  - The relationship between the possible factors affecting pubertal onset and
      pubertal timing was investigated in the Denizli province in Turkey. A total
      number of 3311 subjects (1562 girls, 1749 boys) aged 6-16.5 years participated in
      this study. Body mass index (BMI) was calculated. Pubertal stages were assessed
      according to methods of Marshall and Tanner. Testicular volume was determined
      using Prader orchidometer. Menarcheal age was recorded. All parents and students
      completed different questionnaires on demographic variables affecting pubertal
      timing such as socioeconomic conditions, psychosocial factors, exercise,
      nutritional status, chronic diseases, migration and birth weight. Using
      distribution percentiles of pubertal stages according to age, the relation
      between pubertal timing and factors affecting puberty was investigated. There was
      no significant association between exercise, birth weight, migration, chronic
      disease, and socioeconomic status and age of puberty onset. Menarcheal age of
      overweight and obese girls was significantly lower than that of girls with normal
      weight. In-family stress was the cause of early puberty in girls and of delayed
      puberty in boys.

PMID- 19378892
TI  - Interactions between exhaled CO, smoking status and nicotine dependency in a
      sample of Turkish adolescents.
AB  - The aim of this study was to show the interactions between nicotine dependency,
      exhaled carbon monoxide (CO) and smoking status including environmental passive
      tobacco smoke exposure in a sample of Turkish adolescents. This study was a cross
      sectional research conducted among high school students of Erzurum province
      (n=536). The level of exhaled CO of all participants who accepted to participate
      in the study was measured by Microbio CO Analyzer (Microbio Med). Nicotine
      dependency was measured by a six-item version of the Fagerstrom Tolerance
      Questionnaire. Mean age of the adolescents was 17.0 +/- 1.6 (median: 17) and
      77.1% were male. Of the study population, 30.2% and 11.4% of the students were
      regular and occasional smokers, respectively. Non-smokers who were exposed to
      environmental tobacco smoke had significantly (p<0.01) higher exhaled CO levels
      (2.8 +/- 2.6 ppm) than not-exposed non- smokers (1.8 +/- 1.9 ppm). Only 8.6% of
      adolescents who reported themselves to be a regular smoker had 7 ppm and higher
      exhaled CO. There was a statistically significant and positive correlation
      between exhaled CO levels and nicotine dependency after controlling for
      environmental tobacco smoke exposure and cigarettes per day (partial correlation,
      r=0.334, p=0.004). Exhaled CO can be used as a predictor of smoking status and
      environmental tobacco smoke exposure and an indicator of nicotine dependency in
      adolescents.

PMID- 19378893
TI  - Laryngeal foreign body mistreated as recurrent laryngitis and croup for one year.
AB  - Foreign body aspiration (FBA) is a common, dangerous problem among children of
      all ages. Laryngeal foreign bodies may present with less severe symptoms compared
      to lower respiratory tract foreign bodies, resulting in misdiagnosis, confusion
      and delay. We present the case of a 20-month-old girl with laryngeal foreign body
      unrecognized for one year. She was treated for recurrent laryngitis and
      infectious croup several times. A triangular-shaped, red plastic material with
      sharp edges was removed from the larynx by direct laryngoscopy. The clinical
      presentation and management are discussed.

PMID- 19378894
TI  - Animal carcass and eyelid anthrax: a case report.
AB  - Anthrax is a worldwide zoonosis of herbivores, which is caused by the spore
      forming bacteria Bacillus anthracis, and humans become infected when they are
      exposed to infected animals and their tissues or the organism directly. In this
      report, we present a 13-year-old boy who developed eyelid anthrax after contact
      with a sheep carcass during his summer holiday that resulted in eyelid anthrax
      and cicatricial ectropion.

PMID- 19378895
TI  - Successful treatment with gemtuzumab ozogamicin monotherapy in a pediatric
      patient with resistant relapse of acute myeloid leukemia.
AB  - There are few therapeutic options in relapsed or refractory acute myeloid
      leukemia patients. CD33 antigen is expressed on approximately 90% of myeloblasts,
      and gemtuzumab ozogamicin, as a monoclonal antibody directed against the CD33
      surface antigen, may be a good target for these patients. Herein, we present a 15
      year-old acute myeloid leukemia patient who was resistant at relapse and could
      achieve remission with gemtuzumab ozogamicin at a total dose of 9 mg/m2, divided
      into three doses and delivered to hematopoietic stem-cell transplantation;
      however, the patient relapsed in a short time without application of
      transplantation.

PMID- 19378896
TI  - Cerebral vasculitis and obsessive-compulsive disorder following varicella
      infection in childhood.
AB  - Varicella is largely a childhood disease, with more than 90% of cases occurring
      in children younger than 10 years. The primary infection is characterized by
      generalized vesicular dermal exanthemas, which are extremely contagious.
      Secondary bacterial infection and varicella pneumonia, usually seen in the
      immunocompromised or adult populations, may have high morbidity and mortality.
      Varicella in childhood is a generally benign and self-limited disorder; however,
      severe, life-threatening neurological complications may occur. We report a
      previously healthy eight-year-old boy who presented with acute hemiplegia and
      obsessive-compulsive disorder secondary to a lesion in lentiform nuclei
      associated with a history of recent varicella infection. The child was treated
      with sertraline for obsessive-compulsive disorder symptoms and made a full
      recovery.

PMID- 19378897
TI  - Antiepileptic hypersensitivity and DRESS syndrome due to phenytoin in two
      pediatric cases.
AB  - Antiepileptic hypersensitivity syndrome (AHS) is a potentially life-threatening
      syndrome, especially in pediatric cases. Drug rash with eosinophilia and systemic
      symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs.
      We report here two children with AHS due to phenytoin. Both cases were under
      treatment with phenytoin: the first case was a seven-year-old boy who was
      referred with the classic form of AHS. The second patient was a five-year-old
      girl who manifested with DRESS. The manifestations in both cases improved after
      withholding the phenytoin. Clinical presentations of adverse drug reactions are
      highly variable and must therefore be suspected in any patient who develops any
      unusual manifestation after taking antiepileptic drugs. Early recognition of AHS
      and withholding and/or changing the medication are necessary to prevent
      potentially fatal outcomes.

PMID- 19378898
TI  - A case report with type II pleuropulmonary blastoma: successful treatment with
      surgery and chemotherapy.
AB  - Pleuropulmonary blastoma (PPB) is a very rare intrathoracic malignancy in
      childhood. It is an aggressive embryonal or blastemic neoplasm usually occurring
      in children younger than five years of age. PPB is treated with aggressive
      multimodal therapies consisting of surgery and chemotherapy. We present a case
      with PPB type II successfully treated with complete surgical resection following
      neoadjuvant chemotherapy. She has been free of disease for 33 months of follow
      up. Complete surgical resection of the tumor at the time of diagnosis is the
      cornerstone of PPB management, but in the majority of patients, initial surgery
      is incomplete because a large tumor may involve vital structures. For this
      reason, patients with initially unresectable tumors should be treated with
      neoadjuvant chemotherapy to reduce the lesion to the point that it becomes
      resectable.

PMID- 19378899
TI  - Aneurysmal bone cyst of rib presenting as a huge chest wall mass.
AB  - Aneurysmal bone cyst is a rare benign tumor of the bone that can be difficult to
      distinguish from malignant tumors, especially when it presents in an unusual
      location. Herein, we report a six-year-old girl with a primary aneurysmal bone
      cyst in an uncommon location. It originated from the 4th rib and she presented
      with a huge chest wall mass. Despite the large size of the cyst, the only symptom
      was persistent cough. She was successfully treated with total excision of tumor
      without any complication. The patient has been followed up for 56 months without
      any recurrence.

PMID- 19378900
TI  - Postherpetic pruritus in a child with retinoblastoma.
AB  - Herpes zoster is a painful neurocutaneous disease caused by the reactivation of
      the varicella zoster virus, and it can develop any time after a primary
      infection, which usually occurs during childhood. A variety of immunocompromised
      patient populations are known to be at increased risk for herpes zoster.
      Postherpetic pruritus is a serious complication, which may last after the
      infection, and has the potential to cause injury and disability. The medical
      literature on postherpetic pruritus is very limited. This is a case report of a
      six-year-old child who developed postherpetic pruritus lasting three months,
      which responded to topical urea treatment.

PMID- 19378901
TI  - Management of central diabetes insipidus with oral desmopressin in a patient with
      ectrodactyly and cleft lip/palate (ECP) syndrome.
AB  - We present a female infant with facial abnormalities such as bilateral cleft lip
      and palate, ectrodactyly and central diabetes insipidus. She had a history of
      recurrent hypernatremic attacks and she was treated successfully with oral
      desmopressin. As an alternative to the nasal route, long-term management was
      achieved using oral route and she had a favorable growth and development during
      infancy.

PMID- 19378902
TI  - A case of Hirschsprung disease: does thyroid hormone have any effect?
AB  - Hirschsprung disease, the colonization defect of neural crest cells through the
      colon, is one of the reasons for functional obstruction in neonates. Furthermore,
      hypothyroidism has been known to be one of the causes of bowel hypomotility and
      pseudoobstruction. These two diseases are generally considered in the
      differential diagnosis. Although defective thyroid function has been found to be
      responsible for inappropriate neuronal migration in the brain, the effect of
      thyroid hormone on neural crest cell migration to the bowel has not yet been
      evaluated. Here, we report a case with Hirschsprung disease and congenital
      hypothyroidism, which may point to the need for future studies evaluating the
      interaction of colonic neural crest cell colonization and thyroid hormone.

PMID- 19378903
TI  - History of space medicine: the formative years at NASA.
AB  - Almost nothing was known about the effects of spaceflight on human physiology
      when, in May of 1961, President John F. Kennedy committed the United States to
      land a man on the Moon and return him safely to Earth within the decade. There
      were more questions than answers regarding the effects of acceleration,
      vibration, cabin pressure, CO2 concentration, and microgravity. There were known
      external threats to life, such as solar and ultraviolet radiation, meteorites,
      and extreme temperatures as well as issues for which the physicians and
      scientists could not even formulate the questions. And there was no time for
      controlled experiments with the required numbers of animal or human subjects. Of
      necessity, risks were evaluated and mitigated or accepted based on minimal data.
      This article summarizes presentations originally given as a panel at the 79th
      Annual Scientific Meeting of the Aerospace Medical Association in Boston in 2008.
      In it, five pioneers in space medicine at NASA looked back on the development of
      their field. The authors related personal anecdotes, discussed the roles of
      various people and presented examples of contributions to emerging U.S.
      initiatives for human spaceflight. Topics included the development of quarantine
      facilities for returning Apollo astronauts, the struggles between operational
      medicine and research personnel, and observations from the first U.S. medical
      officer to experience weightlessness on orbit. Brief biographies of the authors
      are appended to document their participation in these historic events.

PMID- 19378904
TI  - Ventilated vest and tolerance for intermittent exercise in hot, dry conditions
      with military clothing.
AB  - INTRODUCTION: Recent research has focused on developing air-ventilated garments
      to improve evaporative cooling in military settings. This study assessed a
      ventilated vest (Vest) in hot (45 degrees C), dry (10% RH) ambient conditions
      over 6 h of rest and exercise. It was hypothesized that the Vest would lower the
      thermal strain and increase the amount of exercise done by subjects. METHODS:
      Eight healthy heat-acclimated men, wearing combat clothing, body armor, and a 19
      kg load in webbing walked on a treadmill at 5 km h(-1) at a 2% incline until
      rectal temperature (T(rec)) reached 38.5 degrees C. They then rested until T(re)
      reached 38 degrees C, at which point they recommenced walking. On one occasion
      the subjects wore a Vest, blowing ambient air around the torso. On the second
      occasion subjects did not wear the vest (NoVest). Exercise/rest ratio, T(rec),
      skin temperature (T(sk)), sweat responses, rating of perceived exertion (RPE),
      and thermal comfort (TC) were measured. RESULTS: Subjects wearing theVest
      exercised for significantly longer (18%; 11 min/h) as a percentage of total
      exposure time, stopped exercise significantly less often [Mean (SD); NoVest: 3
      (2) stops; Vest: 1 (2) stops], and maintained significantly lower skin
      temperature under the body armor [T(chest): NoVest 37.55 (0.51) degrees C; Vest:
      35.33 (1.00) degrees C; T(back): NoVest: 36.85 (0.83) degrees C; Vest: 35.84
      (0.88) degrees C]. The Vest provided 28 W of cooling during exercise and 73 W
      when at rest as estimated by thermometry. CONCLUSION: A ventilated vest can
      provide cooling, and thereby reduce thermal strain and increase exercise done in
      dry environmental temperatures up to 45 degrees C, without causing skin
      irritation and discomfort.

PMID- 19378905
TI  - Changes in visual function during the Coriolis illusion.
AB  - BACKGROUND: The Coriolis illusion produces spatial disorientation and is,
      therefore, dangerous for pilots. It is not known whether it also affects visual
      function (visual acuity and stereopsis). METHODS: There were 18 subjects (15 men
      and 3 women, mean age 24.7 yr) enrolled in the study. A spatial disorientation
      simulator was used to produce Coriolis stimulation. The visual acuity of the
      subjects was evaluated with the Rosenbaum Vision Card before and during Coriolis
      stimulation. Stereopsis was measured with the Titmus stereo test. Throughout the
      experiments, eyeball movements were observed on a television monitor.
      Electrooculography (EOG) and electroencephalography (EEG) were also documented.
      RESULTS: Before Coriolis stimulation, the visual acuity and stereopsis of all
      subjects were 20/20 and 40 s of arc, respectively. During the Coriolis illusion,
      the visual acuity of nine subjects (50%) remained 20/20, whereas the visual
      acuity of the others (50%) dropped by two lines. The stereopsis of most subjects
      (77.8%) decreased to 800 arc-seconds or less. Rhythmic nystagmus was observed,
      while EOG amplitudes were significantly elevated compared with those at baseline
      (9.41 +/- 0.26 microv2 and 8.45 +/- 0.36 microv2, respectively). EEG activity
      (frequency) was also greater than at baseline (13.15 +/- 0.84 Hz and 11.94 +/-
      1.20 Hz, respectively; P < 0.05). CONCLUSIONS: During Coriolis stimulation, the
      visual acuity of the subjects remained stable, but their stereopsis was reduced.
      Further study is warranted.

PMID- 19378906
TI  - Pilot workload during approaches: comparison of simulated standard and noise
      abatement profiles.
AB  - INTRODUCTION: A new noise-reduced landing approach was tested--a Segmented
      Continuous Descent Approach (SCDA)-with regard to the resulting workload on
      pilots. METHODS: Workload of 40 pilots was measured using physiological (heart
      rate, blood pressure, blink frequency, saliva cortisol concentration) and
      psychological (fatigue, sleepiness, tension, and task load) parameters.
      Approaches were conducted in A320 and A330 full-flight simulators during night
      shift. SCDA was compared to the standard Low Drag Low Power (LDLP) procedure as
      reference. RESULTS: Mean heart rate and blood pressure during the SCDA were not
      elevated, but were partly, even significantly, reduced (on average by 5 bpm and 4
      mmHg from the flying captain). Cortisol levels did not change significantly with
      mean values of 0.9 to 1.2 ng ml(-1). Landing was the most demanding segment of
      both approaches as indicated by significant increases in heart rate and decreases
      in blink frequency. Subjective task load was low. DISCUSSION: Both approach
      procedures caused a similar workload level. Interpreting the results,
      methodological limitations have to be considered, e.g., the artificial and
      controlled airspace situation in the flight simulator. Nevertheless, it can be
      concluded that under these ideal conditions, the SCDA is operable without a
      higher workload for pilots compared to the common LDLP.

PMID- 19378907
TI  - Pulmonary barotrauma in divers during emergency free ascent training: review of
      124 cases.
AB  - INTRODUCTION: Experience from treating diving accidents indicates that a large
      proportion of divers suffering from pulmonary barotraumas (PBT) or arterial gas
      embolism (AGE) were engaged in training dives, specifically emergency free ascent
      (EFA). We tried to verify this relationship and to calculate, if possible, the
      risk associated with normal recreational dives, training dives, and EFA training
      dives. METHODS: All diving accidents treated at the Centre for Hyperbaric Oxygen
      Therapy (Brussels, Belgium) from January 1995 until October 2005 were reviewed.
      Data on the average number of dives performed and the proportion of in-water
      skills training dives were obtained from the major Belgian dive associations.
      RESULTS: A total of 124 divers were treated, of whom 34 (27.4%) were diagnosed
      with PBT. Of those, 20 divers (58.8%) had symptoms of AGE. In 16 of those, EFA
      training exercise was deemed responsible for the injury. The association between
      EFA training and PBT proved to be very significant, with an odds ratio of 11.33
      (95% confidence interval: 2.186 to 58.758). It was possible to calculate that a
      training dive (0.456 to 1.36/10,000) carries a 100 to 400 times higher risk, and
      an ascent training dive (1.82 to 5.46/10,000 dives) a 500 to 1500 times higher
      risk for PBT than a non-training dive (0.0041 to 0.0043/10,000 dives).
      DISCUSSION: This study confirms a significant association between EFA training
      dives and the occurrence of PBT.

PMID- 19378908
TI  - Catecholamine levels in hypoxia-lnduced acute mountain sickness.
AB  - Enhanced sympathoadrenal activity has been implicated in the pathogenesis of
      acute mountain sickness (AMS). This study was designed to examine the time course
      of circulating catecholamines in individuals with and without AMS. METHODS:
      Subjects were low-altitude residents (10 men, 8 women) who had not been exposed
      to altitude within the previous 2 mo. They breathed 12% O2 (hypoxia equivalent to
      4600 m altitude) for 8 h while seated at rest. AMS was evaluated using Lake
      Louise scores (LLS) at 0, 1, 3, 5, and 7 h of exposure using a threshold of 3 to
      define AMS. Blood samples were collected to measure arterial blood gases and
      oxygen saturation as well as arterial and venous epinephrine (A-EPI and V-EPI)
      and norepinephrine (A-NE and V-NE). RESULTS: Eight subjects (44%) developed AMS
      at some time during the experiment. Blood gases showed no significant difference
      between subjects with or without symptoms (AMS+ and AMS-, respectively). However,
      AMS+ subjects showed significantly greater concentrations of A-EPI over the 8 h
      without any between-group difference in V-EPI. Levels of A-NE were significantly
      higher at baseline and during the first hour of hypoxia in subjects who later
      developed AMS. V-NE increased significantly over time among all participants with
      no difference between groups. CONCLUSIONS: These findings suggest a possible
      physiological marker for individuals who may be relatively susceptible to AMS and
      provide additional insight into the sympathoadrenal response to acute hypoxia.

PMID- 19378909
TI  - Crash rates of scheduled commuter and air carrier flights before and after a
      regulatory change.
AB  - INTRODUCTION: In 1997, in an effort to reduce the crash rate of scheduled
      commuter flights, the FAA required aircraft with 10-30 passenger seats to operate
      under stricter rules. Training and other requirements of 14 CFR Part 121 rules
      were applied to these midsize commuters, which previously had operated under the
      less strict Part 135 rules. Published crash rates obscured changes related to
      aircraft size. This research was undertaken to determine whether the rule change
      affected crash rates of aircraft with 10-30 passenger seats. METHOD: We
      determined the number of passenger seats on each Part 135 or Part 121 aircraft
      that crashed between 1983 and 2007. For aircraft with < 10, 10-30, and > 30
      seats, we estimated the numbers of departures and crash rates, adjusting for
      changes in total departures and numbers of in-service aircraft. RESULTS: The Part
      135 crash rate tripled in 1997 when commuters with 10-30 seats were excluded,
      reflecting the administrative change. However, the crash rate of aircraft with 10
      30 passenger seats began to decline 4 yr before the rule change; thereafter,
      their rate was lower than for larger aircraft. The fleet size of aircraft with 10
      30 passenger seats increased from 1983 to 1997, then declined as they were
      replaced with larger aircraft in response to the rule change. DISCUSSION: No
      effect of the rule change on crash rates of 10-30-seat aircraft was apparent. The
      decline in their crash rates began before the rule change and may have been
      related to the 1992 requirement for ground proximity warning devices.

PMID- 19378910
TI  - Geographic region, weather, pilot age, and air carrier crashes: a case-control
      study.
AB  - BACKGROUND: Information about risk factors of aviation crashes is crucial for
      developing effective intervention programs. Previous studies assessing factors
      associated with crash risk were conducted primarily in general aviation, air
      taxis, and commuter air carriers. METHODS: A matched case-control design was used
      to examine the associations of geographic region, basic weather condition, and
      pilot age with the risk of air carrier (14 CFR Part 121) crash involvement. Cases
      (N = 373) were air carrier crashes involving aircraft made by Boeing, McDonnell
      Douglas, and Airbus recorded in the National Transportation Safety Board's
      aviation crash database during 1983 through 2002, and controls (N = 746) were air
      carrier incidents involving aircraft of the same three makes selected at random
      from the Federal Aviation Administration's aviation incident database. Each case
      was matched with two controls on the calendar year when the index crash occurred.
      Conditional logistic regression was used for statistical analysis. RESULTS: With
      adjustment for basic weather condition, pilot age, and total flight time, the
      risk of air carrier crashes in Alaska was more than three times the risk for
      other regions ladjusted odds ratio (OR) 3.18, 95% confidence interval (CI) 1.35
      7.49]. Instrument meteorological conditions were associated with an increased
      risk for air carrier crashes involving pilot error (adjusted OR 2.26, 95% CI 1.15
      4.44) and a decreased risk for air carrier crashes without pilot error (adjusted
      OR 0.60, 95% CI 0.37-0.96). Neither pilot age nor total flight time were
      significantly associated with the risk of air carrier crashes. CONCLUSIONS: The
      excess risk of air carrier crashes in Alaska and the effect of adverse weather on
      pilot-error crashes underscore the importance of environmental hazards in flight
      safety.

PMID- 19378911
TI  - Focused ultrasound: concept for automated transcutaneous control of hemorrhage in
      austere settings.
AB  - BACKGROUND: High intensity focused ultrasound (HIFU) is being developed for a
      range of clinical applications. Of particular interest to NASA and the military
      is the use of HIFU for traumatic injuries because HIFU has the unique ability to
      transcutaneously stop bleeding. Automation of this technology would make possible
      its use in remote, austere settings by personnel not specialized in medical
      ultrasound. Here a system to automatically detect and target bleeding is tested
      and reported. METHODS: The system uses Doppler ultrasound images from a clinical
      ultrasound scanner for bleeding detection and hardware for HIFU therapy. The
      system was tested using a moving string to simulate blood flow and targeting was
      visualized by Schlieren imaging to show the focusing of the HIFU acoustic waves.
      RESULTS: When instructed by the operator, a Doppler ultrasound image is acquired
      and processed to detect and localize the moving string, and the focus of the HIFU
      array is electronically adjusted to target the string. Precise and accurate
      targeting was verified in the Schlieren images. CONCLUSIONS: An automated system
      to detect and target simulated bleeding has been built and tested. The system
      could be combined with existing algorithms to detect, target, and treat clinical
      bleeding.

PMID- 19378912
TI  - Ventilatory responses to exercise and hypercapnia following 18 days of head-down
      rest.
AB  - INTRODUCTION: The effects of head-down rest (HDR) and microgravity on
      cardiovascular control have been widely studied; however, their effects on
      ventilatory control are less clear. An increased ventilatory response to exercise
      and/or to hypercapnia (HCVR) could cause significantly increased ventilatory
      demand and/or dyspnea, and thus limit the ability of flight crew to perform high
      intensity exercise during or after spaceflight. Based on limited previous
      studies, we hypothesized that the ventilatory response to exercise would be
      increased, while the HCVR would be decreased after HDR. METHODS: In 21 healthy
      subjects, ventilatory responses to submaximal exercise and to hypercapnia were
      tested before and immediately after 18 d of HDR. Subjects were randomly assigned
      to either daily supine cycle exercise (Exercise group; N = 14, 2 women) or no
      exercise (Rest group; N = 7, 1 woman) during HDR. RESULTS: The exercise
      ventilatory response (DeltaV(E)/DeltaV(CO2)) and the HCVR were unchanged
      following HDR in both groups. However, ventilation was significantly elevated
      after HDR at rest, during submaximal exercise, and while breathing 6% CO2. End
      tidal P(CO2) was significantly reduced at rest, during submaximal exercise, and
      while breathing 3% CO2, indicating a decrease in the CO2 set point. DISCUSSION:
      Although HDR had no effect on the ventilatory responses to exercise and
      hypercapnia, the CO2 set point appeared to be reduced, suggesting an increase in
      drive to breathe that occurred regardless of whether or not subjects undertook
      exercise during HDR. These preliminary results indicate that further study of the
      effects of HDR on ventilatory control is warranted.

PMID- 19378913
TI  - Aircraft mishap investigation with radiology-assisted autopsy: helicopter crash
      with control injury.
AB  - Radiology-assisted autopsy traditionally has been plain film-based, but now is
      being augmented by computed tomography (CT). The authors present a two-fatality
      rotary wing crash scenario illustrating application of advanced radiographic
      techniques that can guide and supplement the forensic pathologist's physical
      autopsy. The radiographic findings also have the potential for use by the
      aircraft mishap investigation board. Prior to forensic autopsy, the two crash
      fatalities were imaged with conventional two-dimensional radiographs (digital
      technique) and with multidetector CT The CT data were used for multiplanar two
      dimensional and three-dimensional (3D) image reconstruction. The forensic
      pathologist was provided with information about skeletal fractures, metal
      fragment location, and other pathologic findings of potential use in the physical
      autopsy. The radiologic autopsy served as a supplement to the physical autopsy
      and did not replace the traditional autopsy in these cases. Both individuals
      sustained severe blunt force trauma with multiple fractures of the skull, face,
      chest, pelvis, and extremities. Individual fractures differed; however, one
      individual showed hand and lower extremity injuries similar to those associated
      with control of the aircraft at the time of impact. The concept of "control
      injury" has been challenged by Campman et al., who found that control surface
      injuries have a low sensitivity and specificity for establishing who the pilot
      was in an accident. The application of new post mortem imaging techniques may
      help to resolve control injury questions. In addition, the combination of
      injuries in our cases may contribute to further understanding of control surface
      injury patterns in helicopter mishaps.

PMID- 19378914
TI  - AED use in a passenger during a long-haul flight: repeated defibrillation with a
      successful outcome.
AB  - INTRODUCTION: Sudden cardiac arrest is one of the leading causes of death, and
      early defibrillation of ventricular fibrillation (VF) is the single most
      important intervention for improving survival. The automated external
      defibrillator (AED) and the concept of public access defibrillation provide a
      solution to shorten defibrillation delays. Commercial aircraft create a unique
      environment for the use of the AED since an emergency medical service system
      (EMS) response is not available. We review published studies on this subject and
      describe the case of a passenger who developed VF during an intercontinental
      flight and was successfully resuscitated despite recurrent episodes of VF. CASE
      REPORT: A 60-yr-old man developed VF during a flight from Tokyo to Helsinki. VF
      frequently recurred and shocks were delivered 21 times altogether. The aircraft
      was diverted to the city of Kuopio. When the local EMS crew encountered the
      patient 3 h after the onset of the cardiac arrest, the rhythm again converted to
      VF and three further shocks were delivered. The patient recovered, and 3 wk later
      he was transported to his home country, fully alert. DISCUSSION: There are three
      large studies reporting placing AEDs on commercial aircraft. No harm for co
      passengers or malfunctions were reported. Survival rates have been higher than
      those obtained by well-performing EMS. According to previous studies, placing
      AEDs on commercial aircraft is also cost effective. The absence of a suitable
      diversion destination should not influence the rescuers' decision to attempt CPR
      on board.

PMID- 19378915
TI  - Visual display angles of conventional and a remotely piloted aircraft.
AB  - INTRODUCTION: Instrument display separation and proximity are important human
      factor elements used in the design and grouping of aircraft instrument displays.
      To assess display proximity in practical operations, the viewing visual angles of
      various displays in several conventional aircraft and in a remotely piloted
      vehicle were assessed. METHODS: The horizontal and vertical instrument display
      visual angles from the pilot's eye position were measured in 12 different types
      of conventional aircraft, and in the ground control station (GCS) of a remotely
      piloted aircraft (RPA). A total of 18 categories of instrument display were
      measured and compared. RESULTS: In conventional aircraft almost all of the
      vertical and horizontal visual display angles lay within a "cone of easy eye
      movement" (CEEM). Mission-critical instruments particular to specific aircraft
      types sometimes displaced less important instruments outside the CEEM. For the
      RPA, all horizontal visual angles lay within the CEEM, but most vertical visual
      angles lay outside this cone. DISCUSSION: Most instrument displays in
      conventional aircraft were consistent with display proximity principles, but
      several RPA displays lay outside the CEEM in the vertical plane. Awareness of
      this fact by RPA operators may be helpful in minimizing information access cost,
      and in optimizing RPA operations.

PMID- 19378916
TI  - Sponge divers of the Aegean and medical consequences of risky compressed-air dive
      profiles.
AB  - Historically, Turkey once had a substantial number of professional sponge divers,
      a population known for a relatively high incidence of diving-related conditions
      such as decompression sickness (DCS) and dysbaric osteonecrosis (DON). Sponge
      diving ended in the mid-1980s when nearly all of the sponges in the Aegean and
      Mediterranean Seas contracted a bacterial disease and the occupation became
      unprofitable. We reviewed the records of Turkish sponge divers for information on
      their level of knowledge, diving equipment, dive profiles, and occupational
      health problems. Information was collected by: 1) interviewing former sponge
      divers near Bodrum, where most of them had settled; 2) reviewing the relevant
      literature; and 3) examining the medical records of sponge divers who underwent
      recompression treatment. These divers used three types of surface-supplied
      equipment, including hard helmets, Fernez apparatus, and hookahs; the latter were
      preferred because they allowed divers the greatest freedom of movement while
      harvesting sponges underwater. These divers used profiles that we now know
      involved a high risk for DCS and DON. We were able to access the records of 58
      divers who had received recompression treatment. All of the cases involved severe
      DCS and delays from dive to recompression that averaged 72 h. Complete resolution
      of symptoms occurred in only 11 cases (19%). Thus, we were able to document the
      several factors that contributed to the risks in this occupational group,
      including unsafe dive profiles, resistance to seeking treatment, long delays
      before recompression, and the fact that recompression treatment used air rather
      than oxygen.

PMID- 19378917
TI  - Fatigue countermeasures and the use of hypnotics in aircrew.

PMID- 19378918
TI  - Automatic Dependent Surveillance-Broadcast (ADS-B)--the first step in the FAA's
      next-generation air transportation system.

PMID- 19378919
TI  - Type of cell death and the role of acetylcholinesterase activity in neurotoxicity
      induced by paraoxon in cultured rat hippocampal neurons.
AB  - Organophosphate (Ops) neurotoxicity is attributed both to its well-known
      cholinergic and non-cholinergic effects. In the present study we compared
      enzymatic and morphologic changes in neurons exposed to paraoxon during one day
      and one week. The effect of exposure time is important in neurotoxicity of Ops.
      The longer the exposure time is the more damage is observed in neurons, although
      there are few investigations about the effect in the post-exposure period.
      Hippocampal cells were obtained from rat neonates and cultured in Neurobasal/B27.
      Paraoxon at 50 and 100 microM were added. Inverted microscope and electron
      microscope were used to study cell morphology and Neutral Red staining was used
      to measure viability. We also assayed caspase-3 and (acetylcholinesterase) AChE
      activity. Hoechst staining was utilized to determine the type of cell death.
      Culture medium was replaced after 24 h in one-day group, however, tests were all
      carried out at the end of the first week in both group. The results indicate that
      paraoxon reduced the viability in a dose-dependent manner. Our results do not
      confirm apoptosis in either group; it seems that the cell death in one-day
      exposure group was not AChE dependent. In conclusion, present data imply that the
      toxicity of paraoxon is both dose and duration dependent, which may even remain
      after the cessation of exposure.

PMID- 19378920
TI  - Introducing tetraCys motifs at two different sites results in a functional
      dopamine transporter.
AB  - We have introduced tetracysteine motifs into different positions of the dopamine
      transporter (DAT) for specific FlAsH labeling. Two of the constructs expressed at
      the cell surface and were functional as determined by [3H] dopamine uptake
      experiments. The N-terminally modified transporter showed uptake levels
      comparable to the wild-type DAT, while the construct with tetracysteine motif at
      position 511 displayed an uptake level about 1/3 of its wild-type counterpart. In
      addition, these two transporter constructs were visualized on the cell surface
      following labeling with a fluorescent cocaine analog. YFP introduced into the
      same N-terminal position was also shown to have surface staining in agreement
      with activity tests. We propose that these two sites are suitable targets for
      tetracysteine labeling to be used in FlAsH staining studies, while p134, p342,
      p427, p433 and p517 sites are not.

PMID- 19378921
TI  - Ultrastructure of the mature spermatozoon of the bivalve Estellarca olivacea
      (Mollusca: Bivalvia: Arcidae) and its phylogenetic implications.
AB  - Ultrastructure of mature spermatozoa of Estellarca olivacea was studied by
      transmission electron microscopy and its phylogenetic implications are discussed
      for the first time in this paper. The mature spermatozoon is composed of a head
      which contains a cone-shaped acrosome, a round nucleus and a tail region. The
      subacrosomal space is less electron dense which contains a homogeneous material.
      No axial rod and a basal plate were observed in subacrosomal space. No anterior
      invagination exists in the nucleus, but an inverted shallow V-shaped posterior
      invagination is visible. Nuclear lacunae could be seen clearly although the
      nucleus is highly condensed. Within the mid-piece of the spermatozoon there exist
      five spherical mitochondria while the long whip-like end portion is composed of
      an axoneme with the typical 9+2 structure. The spermatozoon of Estellarca
      olivacea is a product of the evolution of the reproductive system of the family
      Arcidae. Whether the particular acrosome, subacrosomal space, or the highly
      condensed nucleus might be adaptations of high fertilization rate in the
      particular environment of this species is discussed.

PMID- 19378922
TI  - The effects of prometryne on subchronically treated mice evaluated by SCGE assay.
AB  - Prometryne is a methylthio-s-triazine herbicide used to control annual broadleaf
      and grass weeds in many cultivated plants. Significant traces are documented in
      environment, mainly water, soil and plants used for human and domestic animal
      nutrition. Data on the toxic effects of prometryne and other methylthio-s
      triazine have scorcely been published. The goal of this study was to investigate
      if prometryne, applied orally, could induce DNA damage in mouse leukocytes, in
      subchronical in vivo experimental design. Three different doses of prometryne
      were applied per os repeatedly every 48 hours. After the 7th dose (day 14) and
      the 14th dose (day 28) blood leucocytes were analyzed by alkaline Single Cell Gel
      Electrophoresis (Comet) assay. The results of three different comet parameters
      showed general increase in Olive tail moment, tail length and tail intensity
      values in treated groups of animals. The increase in measured values was almost
      proportional to the dose received and the time of exposure. We conclude that
      prometryne or its metabolic residues have the potential to induce processes that
      cause genotoxic effects on leukocytes on mice in in vivo repeated exposure.

PMID- 19378923
TI  - The another toxic effect of carbamate insecticides.
AB  - The activities of the antioxidant and detoxifying enzymes, superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GSHPx), glutathione reductase
      (GR), glutathione-S-transferase (GST), and the content of thiobarbituric acid
      reactive substances (TBARS) were determined in the liver and kidney of rabbits
      after exposure to bendiocarb. In the liver, the activities of SOD, CAT and GR
      were not affected by bendiocarb. The induction or inhibition of isoenzymes of SOD
      (mainly MnSOD) were observed in the experimental groups. The activities of GSHPx
      cum and GSHPx-H2O2 significantly decreased on the days 3 and 10 of the
      experiment. The activity of GST significantly increased on the day 9 of the
      experiment. In the kidney, the activity of SOD was significantly increased and
      the new MnSOD isoenzymes were detected. The activities of CAT and GSHPx-H2O2 were
      significantly decreased in the experimental groups. The activity of GR
      significantly increased on days 3 and 10, and the activity of GST was
      significantly increased on days 3, 10, and 30. Exposure of rabbit to bendiocarb
      did not affect the content of TBARS in the kidney. In the liver, the content of
      TBARS was significantly increased in the experimental groups as compared to the
      control. Our results showed that the response of organs to bendiocarb is
      different and may depend on the specific organ damage and their protective
      abilities. The alterations in the activities of the antioxidant defence system,
      increased TBARS values, and changes in the SOD isoenzyme pattern showed that the
      toxic effect of bendiocarb is not only in the acetylcholine esterase inhibition,
      but also in ROS production.

PMID- 19378924
TI  - Preliminary studies on the effect of zinc and selenium on vanadium-induced
      cytotoxicity in vitro.
AB  - In the present work, we investigated the cytotoxicity of vanadium and the
      influence of zinc and selenium on vanadium-dependent cell damage in the BALB/c
      3T3 cell culture. Treatment of cells for 24 hours with medium containing 50, 100
      and 200 microM NaVO3 caused a significant decrease in the cell viability as
      measured by MTT test. Furthermore, the assays for reactive oxygen species (NBT
      reduction and phenol red oxidation) demonstrated the increase in superoxide and
      hydrogen peroxide production. In the cotreatment studies, the cells were exposed
      to NaVO3 (50, 100 and 200 microM) in the presence of nontoxic concentrations of
      ZnCl2 (5 microM) or Na2SeO3 (0.5 microM). Following 24 h incubation, the cell
      viability (assessed in MTT assay) and reactive oxygen species generation were
      evaluated. Our data suggest that zinc and selenium, in the concentrations
      mentioned above, provide no protection against adverse actions induced by sodium
      metavanadate at concentration levels of 50, 100 and 200 microM. To our knowledge,
      this is the first report from in vitro studies on interaction between pentavalent
      vanadium and trace elements that function as antioxidants: zinc and selenium.

PMID- 19378925
TI  - Antioxidant and antiapoptotic activities of deprenyl and estradiol co
      administration in aged rat kidney.
AB  - Aging is a progressive degeneration process in living organisms. Deprenyl is an
      irreversible monoamine-oxidase B inhibitor which has antioxidant, antiapoptotic
      and neuroprotective effects. Estradiol is also a neuroprotective and antioxidant
      hormone. The objective of this study was to determine whether the antioxidative
      effects of deprenyl can suppress apoptotic activity, with or without estradiol,
      in aged female rat kidney. Wistar Albino female rats were divided into six groups
      as follows; young (3 months old) control, aged (24 months old) control, aged
      deprenyl treated, aged estradiol treated, aged deprenyl plus estradiol treated
      and sham. All rats except for the sham group were injected for 21 days.
      Determination of oxidative stress parameter was performed spectrophotometrically.
      To detect apoptotic cells, TUNEL staining and caspase-3 immunohistochemistry were
      performed. Deprenyl and estradiol administration, alone or in combination,
      decreased significantly the levels of lipid peroxidation relative to aged control
      and sham-injected rats. The number of TUNEL positive cells decreased
      significantly in deprenyl and estradiol-treated rats compared with aged control
      and sham rats. Deprenyl and estradiol replacement attenuated age-related changes
      in renal morphology. The results indicate that deprenyl treatment alone, or in
      combination with estradiol, may modulate age-related apoptotic changes in rat
      kidney by decreasing oxidative stress.

PMID- 19378926
TI  - Changes in antioxidant status and biochemical parameters after orally cadmium
      administration in females rats.
AB  - The research was conducted to investigate the toxic effects of cadmium chloride
      (CdCl2), administered during gestation period on female Wistar rats. Pregnant
      rats received CdCl2 (20 mg/l, orally) from Day 6 to Day 19 of pregnancy. Results
      showed that Cd treatment induced a decrease in body weight gain. The relative
      liver weight increased significantly, with a marked decrease of glycogen and
      total lipids content. The administration of Cd induced hepatotoxicity as
      indicated by elevations in plasma alanine aminotransferase (ALT), aspartate
      aminotransferase and lactate dehydrogenase (LDH) activities (p < 0.05). Treatment
      with CdCl2 caused a significant (p < 0.05) increase in glucose. A significant
      increase was observed in the level of MDA and 8-oxodGuo tissues in the cadmium
      exposed group compared to the control group (p < 0.05). Results showed that
      cadmium given to dams led to an oxidative stress and DNA damage in tissues of
      pregnant rats.

PMID- 19378927
TI  - Comparison of murine fibroblast cell response to fluor-hydroxyapatite composite,
      fluorapatite and hydroxyapatite by eluate assay.
AB  - Fluorapatite (FA) is one of the inorganic constituents of bone or teeth used for
      hard tissue repairs and replacements. Fluor-hydroxyapatite (FHA) is a new
      synthetic composite that contains the same molecular concentration of OH(-)
      groups and F(-) ions. The aim of this experiment was to evaluate the cellular
      responses of murine fibroblast NIH-3T3 cells in vitro to solid solutions of FHA
      and FA and to compare them with the effect of hydroxyapatite (HA). We studied 24,
      48 and 72 h effects of biomaterials on cell morphology, proliferation and cell
      cycle of NIH-3T3 cells by eluate assay. Furthermore, we examined the ability of
      FHA, FA and HA to induce cell death and DNA damage. Our
      cytotoxic/antiproliferative studies indicated that any of tested biomaterials did
      not cause the total inhibition of cell division. Biomaterials induced different
      antiproliferative effects increasing in the order HA < FHA < FA which were time-
      and concentration-dependent. None of the tested biomaterials induced
      necrotic/apoptotic death of NIH-3T3 cells. On the other hand, after 72 h we found
      that FHA and FA induced G0/G1 arrest of NIH-3T3 cells, while HA did not affect
      any cell cycle phases. Comet assay showed that while HA demonstrated weaker
      genotoxicity, DNA damage induced by FHA and FA caused G0/G1 arrest of NIH-3T3
      cells. Fluoridation of hydroxyapatite and different FHA and FA structure caused
      different cell response of NIH-3T3 cells to biomaterials.

PMID- 19378928
TI  - A comparative analysis of fatty acid composition of root and shoot lipids in Zea
      mays under copper and cadmium stress.
AB  - A comparative analysis of fatty acid composition was conducted in maize (Zea mays
      L.) under copper and cadmium stress. The unsaturation level (double-bond index)
      of phosphatidylethanolamine (PE) and digalactosyldiacylglycerol (DGDG) was
      increased in response to both metal treatments, whereas the phosphatidylinositol
      (PI), the phosphatidylcholine (PC) showed no significant changes. The Cu-treated
      roots showed a marked increase (about 2-fold) in the phospholipid (PL) content,
      while the Cd-treated roots showed a slight but insignificant increase. The steryl
      lipid SL/PL ratio was markedly decreased in response to Cu stress, and therefore,
      may indicate an activated phospholipid biosynthesis and turnover, in response to
      damage caused by Cu stress. The double bond indices of chloroplastic lipids:
      phosphatidylglycerol (PG), monogalactosyldiacylglycerol (MGDG),
      digalactosyldiacylglycerol (DGDG) and sulfoquinovosyldiacylglycerol (SQDG)
      revealed a similar but not identical pattern of change. The PG and MGDG contents
      in shoots were markedly decreased under Cu (by 53 and 48%) and Cd (by 78 and 65%)
      stress. The increase in the malondialdehyde (MDA) content in roots induced by
      both metals indicates lipid peroxidation. Generally, in the presence of Cu fatty
      acid composition was markedly modulated but to lesser extent under Cd stress.
      These results suggest that changes in the fatty acid composition under Cu and Cd
      stress conditions are metal-specific and may therefore result in differential
      metal tolerance.

PMID- 19378929
TI  - Thermal inactivation kinetics of Lactococcus lactis subsp. lactis bacteriophage
      pll98-22.
AB  - Survival curves of Lactococcus lactis subsp. lactis bacteriophage pll98
      inactivated by heat were obtained at seven temperature values (50-80 degrees C)
      in M17 broth and skim milk. Deviations from first-order kinetics in both media
      were observed as sigmoidal shapes in the survival curves of pll98. An empirical
      model with four parameters was used to define the thermal inactivation. Number of
      parameters of the model was reduced from four to two in order to increase the
      robustness of the model. The reduced model produced comparable fits to the full
      model. Both the survival data and the calculations done using the reduced model
      (time necessary to reduce the number of phage pll98 six- or seven- log10)
      indicated that skim milk is a more protective medium than M17 broth within the
      assayed temperature range.

PMID- 19378930
TI  - Catalytic asymmetric syntheses of alpha-amino and alpha-hydroxyl acid
      derivatives.
AB  - Herein we report the first room temperature Heck reaction of aryl bromides and
      CH(2)=C(NHP)CO(2)Me (P = Boc or CBz) to form ArCH=C(NHP)CO(2)Me, which are then
      used for the asymmetric syntheses of alpha-amino acids. We also report the first
      syntheses of ArCH=C(OCOAr(1))CO(2)Me (Ar(1) = Ph, 4-Cl-Ph) from ArBr and
      CH(2)=C(OCOAr(1))CO(2)Me by the Heck reaction and subsequent successful
      asymmetric hydrogenation to afford alpha-hydroxyl esters in excellent chemical
      yields and good-to-excellent enantioselectivities.

PMID- 19378931
TI  - Route to smooth silica-based surfaces decorated with novel self-assembled
      monolayers (SAMs) containing glycidyl-terminated very long hydrocarbon chains.
AB  - Novel glycidyl-terminated organosilicon coupling agents possessing a
      trialkoxysilyl head group and a very long hydrocarbon chain (C22) were
      synthesized. Their ability to afford densely packed self-assembled monolayers
      (SAMs) grafted on silica-based surfaces was investigated. Transmission FT-IR
      spectra showed that the most regular films were obtained by using trichloracetic
      acid as the catalyst (10 M%). Atomic force microscopy (AFM) and optical
      ellipsometry were consistent with well ordered monolayers exhibiting a marked
      decrease of the surface roughness. Epifluorescence microscopy revealed that these
      SAMs possessed a better surface reactivity than monolayers obtained with the
      commercially available (3-glycidoxypropyl) trimethoxysilane (GPTS) upon grafting
      of a fluorescent probe (dansylcadaverin). Moreover, direct attachment of
      fluorescent antibodies (RAG-TRITC) through covalent binding led to higher mean
      fluorescence intensities, showing that these new SAMs possess high potential for
      the immobilization of biological molecules.

PMID- 19378933
TI  - Neutron diffraction study of liquid N-methylformamide using EPSR simulation.
AB  - The structure of N-methylformamide (NMF) in liquid state has been investigated
      using a combination of neutron diffraction measurements augmented with isotopic
      substitution and empirical potential structure refinement computer simulations.
      The reference potential used was optimized previously and consisted of Coulomb
      and 6-12 Lennard-Jones interactions for the atoms. The results show that the
      three-dimensional model of the liquid structure constructed at the correct atomic
      number density is consistent with the diffraction experimental data. The liquid
      structure is orientated by the hydrogen bonds among the molecules. Each NMF
      molecule is, on average, hydrogen bonded to two others. The findings indicate
      that dimers and "linear" trimers are very stable species in the liquid bulk.
      Because of that, the liquid is strongly structured into a chain-like structure.
      Neighboring chains are stabilized with respect to each other by weak O...H(C)
      hydrogen bonds. The results are consistent with the known physicochemical
      properties of the liquid.

PMID- 19378934
TI  - Photophysics and photochemistry of an asymmetrically substituted diazene: a
      suitable cage effect probe.
AB  - The photophysics and photochemistry of (1-biphenyl-4-yl-1-methyl-ethyl)-tert
      butyl diazene were thoroughly studied by laser flash photolysis from the
      picosecond to the microsecond time domain. The compound has favorable features as
      a radical photoinitiator and as a probe for cage effect studies in liquids,
      supercritical fluids, and compressed gases. The biphenyl moiety acts as an
      antenna efficiently transferring electronic energy to the dissociative (1)n,pi*
      state centered on the azo moiety. By picosecond experiments irradiating at the
      biphenyl- and at the azo-centered transitions, we were able to demonstrate this
      fact as well as determine a lifetime of 0.7 ps for the buildup of 1-biphenyl-4-yl
      1-methyl-ethyl radicals (BME*). The sum of in-cage reaction rate constants of
      BME* radicals by combination and disproportionation is 5 x 10(10) s(-1). The free
      radical quantum yield in solution is 0.21 (phi(BME*)) in n-hexane at room
      temperature, whereas the dissociation quantum yield approaches 50%. The symmetric
      ketone, 2,4-bis-biphenyl-4-yl-2,4-dimethyl-pentan-2-one, was used as a reference
      compound for the production and reaction of BME* radicals. Transient IR
      measurements show CO stretching bands of the excited (3)pi,pi* and (1)n,pi*
      states but no dissociation up to 0.5 ns. A fluorescence lifetime of 1 ns for this
      ketone is consistent with this observation. By transient actinometry and kinetic
      decays in the microsecond time range, we measured epsilon(BME*) = (2.3 +/- 0.2) x
      10(4) M(-1) cm(-1) at 325 nm and a second-order rate constant of 5.8 x 10(9) M(
      1) s(-1) for the consumption of BME* radicals.

PMID- 19378936
TI  - Structural and photoluminescence studies of a europium(III) tetrakis(beta
      diketonate) complex with tetrabutylammonium, imidazolium, pyridinium and silica
      supported imidazolium counterions.
AB  - Tetrakis(naphthoyltrifluoroacetonato)lanthanate(III) complexes (Ln = Eu, Gd)
      containing the cations tetrabutylammonium, [NBu(4)](+); 1-butyl-3
      methylimidazolium, [C(4)mim](+); and 1-butyl-3-methylpyridinium, [C(4)mpyr](+),
      have been prepared and structurally characterized by single-crystal X-ray
      diffraction. The {EuO(8)} coordination sphere in [NBu(4)][Eu(NTA)(4)] is best
      described as a distorted dodecahedron, where the metal ion is located at the 4
      fold inversion axis with only one crystallographically independent NTA residue.
      In [C(4)mim][Eu(NTA)(4)] and [C(4)mpyr][Gd(NTA)(4)], the central Ln(3+) ions are
      coordinated by eight oxygen atoms from four distinct beta-diketonate ligands, in
      an overall distorted square-antiprismatic geometry. Besides electrostatic
      interactions, the crystal packing in all three structures is stabilized by offset
      pi-pi interactions involving the naphthyl rings of neighboring complexes (and,
      for [C(4)mim][Eu(NTA)(4)] and [C(4)mpyr][Gd(NTA)(4)], neighboring
      naphthyl/imidazolium and naphthyl/pyridinium rings) and C-H...pi contacts. The
      photoluminescence properties of the three Eu(III) complexes were studied at room
      temperature and -259 degrees C by measuring emission and excitation spectra,
      (5)D(0) emission decay curves, and absolute emission quantum yields. Under ligand
      excitation (lambda(ex) = 290-395 nm), the quantum yields (room temperature) were
      in the range 0.72-0.77 for the 1-butyl-3-methylimidazolium salt. An immobilized
      analogue of this complex was prepared by supporting [Eu(NTA)(4)](-) on an ordered
      mesoporous silica derivatized with 1-propyl-3-methylimidazolium groups. The
      disappearance of the intra-4f(6) lines in the excitation spectrum of the
      supported material indicated an increase in the ligand's sensitization process of
      the Eu(3+) ions, relative to direct intra-4f(6) excitation. The emission quantum
      yield measured for the supported material (0.32-0.40, for excitations between 265
      and 360 nm) is the highest so far reported for lanthanide-containing ordered
      mesoporous silicas.

PMID- 19378935
TI  - Comparison of synthetic high density lipoprotein (HDL) contrast agents for MR
      imaging of atherosclerosis.
AB  - Determining arterial macrophage expression is an important goal in the molecular
      imaging of atherosclerosis. Here, we compare the efficacy of two synthetic, high
      density lipoprotein (HDL) based contrast agents for magnetic resonance imaging
      (MRI) of macrophage burden. Each form of HDL was labeled with gadolinium and
      rhodamine to allow MRI and fluorescence microscopy. Either the 37 or 18 amino
      acid peptide replaced the apolipoprotein A-I in these agents, which were termed
      37pA-Gd or 18A-Gd. The diameters of 37pA-Gd and 18A-Gd are 7.6 and 8.0 nm,
      respectively, while the longitudinal relaxivities are 9.8 and 10.0 (mM s)(-1).
      37pA has better lipid binding properties. In vitro tests with J774A.1 macrophages
      proved the particles possessed the functionality of HDL by eliciting cholesterol
      efflux and were taken up in a receptor-like fashion by the cells. Both agents
      produced enhancements in atherosclerotic plaques of apolipoprotein E knockout
      mice of approximately 90% (n = 7 per agent) and are macrophage specific as
      evidenced by confocal microscopy on aortic sections. The half-lives of 37pA-Gd
      and 18A-Gd are 2.6 and 2.1 h, respectively. Despite the more favorable lipid
      interactions of 37pA, both agents gave similar, excellent contrast for the
      detection of atherosclerotic macrophages using MRI.

PMID- 19378938
TI  - New crystalline layered zinc phosphate with 10-membered-ring channels
      perpendicular to layers.
AB  - A novel layered zinc phosphate, [N(2)C(6)H(12)](2)[Zn(7)H(3)(HPO(4
      x))(5)(PO(4))(3)]H(2)O, with unique 10-membered-ring ellipsoidal channels running
      perpendicularly to ladder-shaped tetrahedral layers, has been synthesized
      ionothermally via in situ generation of 1,4-diazabicyclo[2.2.2]octane.

PMID- 19378939
TI  - Palladium diselenolenes: a new group of near-infrared lumophores.
AB  - We describe the photochemical characteristics of two phosphorescent palladium
      diselenolenes [Pd(2)(Se(2)C(8)H(12))(2)(PBu(3))(2)] (1) and
      [Pd(2)(Se(2)C(8)H(12))(2)(PPh(3))(2)] (2) which, to the best of our knowledge,
      are the first reported examples of luminescent Pd-Se compounds. Both compounds
      exhibit broadband near-infrared phosphorescence in the solid state, with
      lambda(max) of 717 nm for 1 and 792 nm for 2 at 298 K, and 752 nm for 1 and 785
      nm for 2 at 77 K. No phosphorescence was detected for either compound when they
      were dissolved in nitrogen-purged acetonitrile or toluene solution at 298 K but
      they do phosphoresce at 77 K in organic glasses with emission quantum yields of
      0.12 (+/-0.01) for 1 and 0.13 (+/-0.01) for 2 in an ethanol/diethylether/toluene
      (1:2:1) (EDT) glass. Emission lifetimes at 77 K are the same whether in the solid
      state or in an organic glass with first order fit lifetimes of tau = 18.8 (+/
      0.7) micros and 11.5 (+/-0.3) micros for 1 and 2, respectively. Combination of
      these lifetimes with quantum yields gives radiative lifetimes of 151 (+/-13)
      micros and 86 (+/-7) micros for compounds 1 and 2, respectively, at 77 K in EDT
      glass. At 77 K solid state quantum yields are estimated to be of the same order
      of magnitude as those in glasses, and these decrease by a factor of about 3-5 in
      going from 77 to 298 K. In the solid state at 298 K emission lifetimes are 1.83
      (+/-0.02) micros and 7.0 (+/-0.3) micros for 1 and 2, respectively. We could
      detect no transients by nanosecond flash photolysis which could be assigned to
      the triplet state in room temperature solution, and no emission assignable to
      singlet oxygen across the wavelength range 1200-1350 nm upon 550 nm excitation of
      either 1 or 2 in acetonitrile solution. We estimate the quantum yield of singlet
      oxygen formation to be less than about 5 x 10(-4), which is also an upper limit
      for the yield of triplet states of any significant lifetime in fluid solution.
      Density functional theory (DFT) calculations of the S(0) to S(1) and T(1)
      transitions show a shift in molecular orbital character from one with significant
      -ene pi involvement but very little P involvement in the ground-state to one with
      less -ene pi but greater P involvement in the excited states; there is also a
      significant shift in the distribution of involvement of atomic orbitals on the
      four Se atoms.

PMID- 19378941
TI  - Copper coordination polymers based on single-chain or sheet structures involving
      dinuclear and tetranuclear copper(II) units: synthesis, structures, and
      magnetostructural correlations.
AB  - Reactions between the potentially pentadentate (N(2)O(3)), trianionic double
      Schiff-base ligand 2,6-bis[[(2-hydroxyethyl)imino]methyl]-4-methylphenol (H(3)L)
      and Cu(CH(3)CO(2))(2) or Cu(ClO(4))(2), in the presence of NaN(3), give novel
      coordination polymers with chain {[Cu(2)(H(2)L)(N(3))(3)](2).H(2)O}(n) (1) or
      sheet [Cu(2)(H(2)L)(N(3))(3)](n) (2) and [Cu(2)(HL)(N(3))](n)[ClO(4)](n) (3)
      structures, respectively. These clusters are comprised of repeating dinuclear
      units (1) or their dimers (2 and 3). In these compounds, H(3)L acts as a
      tridentate (N(2)O) monoanionic (1), tetradentate (ON(2)O) monoanionic (2), or
      pentadentate (O(3)N(2)) dianionic (3) ligand. Compound
      [Cu(2)(HL)(N(3))(2)(H(2)O)].0.5CH(3)OH (4) formed from the reaction of
      Cu(CH(3)CO(2))(2) with H(3)L under reflux, which did not afford crystals suitable
      for X-ray studies. X-ray structure determinations have revealed that the basic
      building block in 1-3 comprises two copper centers bridged through one mu
      phenolate O atom from H(2)L(-) or HL(2-) and one mu-azido(N1,N1) ion. Compounds 1
      3 unveil three different ways in which this Cu(2) basic unit may be organized in
      the crystalline phase at the supramolecular level through a variety of bridging
      interactions involving additional azide ligands or alkoxide groups from the side
      arms of the ligand H(3)L. Bulk magnetization measurements have served to
      demonstrate that the magnetic interactions are completely dominated by the strong
      antiferromagnetic coupling occurring within the Cu(2) building block, with
      coupling constants ranging from 330 to 560 cm(-1) (in the H = -JS(1)S(2)
      convention). These results together have been incorporated with data from the few
      related copper dimers reported exhibiting the same bridging pattern into a study
      aimed at extracting possible magnetostructural correlations within this Cu(2)
      unit. An earlier predicted correlation between J and the angle formed by the
      phenoxide bridge and the Cu(2) core has been identified for the first time.

PMID- 19378940
TI  - Optical signatures of molecular dissymmetry: combining theory with experiments to
      address stereochemical puzzles.
AB  - Modern chemistry emerged from the quest to describe the three-dimensional
      structure of molecules: van't Hoff's tetravalent carbon placed symmetry and
      dissymmetry at the heart of chemistry. In this Account, we explore how modern
      theory, synthesis, and spectroscopy can be used in concert to elucidate the
      symmetry and dissymmetry of molecules and their assemblies. Chiroptical
      spectroscopy, including optical rotatory dispersion (ORD), electronic circular
      dichroism (ECD), vibrational circular dichroism (VCD), and Raman optical activity
      (ROA), measures the response of dissymmetric structures to electromagnetic
      radiation. This response can in turn reveal the arrangement of atoms in space,
      but deciphering the molecular information encoded in chiroptical spectra requires
      an effective theoretical approach. Although important correlations between ECD
      and molecular stereochemistry have existed for some time, a battery of accurate
      new theoretical methods that link a much wider range of chiroptical
      spectroscopies to structure have emerged over the past decade. The promise of
      this field is considerable: theory and spectroscopy can assist in assigning the
      relative and absolute configurations of complex products, revealing the structure
      of noncovalent aggregates, defining metrics for molecular diversity based on
      polarization response, and designing chirally imprinted nanomaterials. The
      physical organic chemistry of chirality is fascinating in its own right: defining
      atomic and group contributions to optical rotation (OR) is now possible. Although
      the common expectation is that chiroptical response is determined solely by a
      chiral solute's electronic structure in a given environment, chiral imprinting
      effects on the surrounding medium and molecular assembly can, in fact, dominate
      the chiroptical signatures. The theoretical interpretation of chiroptical markers
      is challenging because the optical properties are subtle, resulting from the
      strong electric dipole and the weaker electric quadrupole and magnetic dipole
      perturbations by the electromagnetic field. Moreover, OR arises from a
      combination of nearly canceling contributions to the electronic response. Indeed,
      the challenge posed by the chiroptical properties delayed the advent of even
      qualitatively accurate descriptions for some chiroptical signatures until the
      past decade when, for example, prediction of the observed sign of experimental OR
      became accessible to theory. The computation of chiroptical signatures, in close
      coordination with synthesis and spectroscopy, provides a powerful framework to
      diagnose and interpret the dissymmetry of chemical structures and molecular
      assemblies. Chiroptical theory now produces new schemes to elucidate structure,
      to describe the specific molecular sources of chiroptical signatures, and to
      assist in our understanding of how dissymmetry is templated and propagated in the
      condensed phase.

PMID- 19378942
TI  - Simultaneous extraction and cleanup method based on pressurized solvent
      extraction for multiresidue analysis of pesticides in complex feed samples.
AB  - The development of a multiresidue method based on pressurized solvent extraction
      (PSE) to determine a large number of pesticides (mostly pyrethroids and
      organochlorines) in cattle feed is described. As far as we know, this is the
      first work dedicated to the PSE of many of the target pesticides from animal
      feed. A mixed level fraction design was performed to investigate the influence of
      several operational variables on the PSE procedure; integrated cleanup strategies
      were also assessed allowing the direct chromatographic analysis of the extracts.
      Method accuracy was evaluated by the analysis of a certified reference material
      (BCR-115) and different fortified cattle feed samples. Most analytes were
      recovered in the range of 70-110%, with relative standard deviations generally
      lower than 15%. Limits of detection (LODs) were below the maximum residue levels
      (MRLs) set by the European Union for animal feed and main crops used in the
      preparation of feedingstuffs. The applicability of the proposed method was
      demonstrated by the analysis of real cattle feed samples collected from 23 dairy
      farms located in Galicia (NW Spain).

PMID- 19378943
TI  - Multiresidue determination and uncertainty analysis of 87 pesticides in mango by
      liquid chromatography-tandem mass spectrometry.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method was
      optimized and validated for the multiresidue analysis of 87 pesticides in mango
      at the <= 10 ng g(-1) level. The method involves extraction of 10 g of
      homogenized mango samples (+10 mL of water + 1 g of sodium acetate + 10 g of
      sodium sulfate) with 10 mL of ethyl acetate; cleanup by dispersive solid-phase
      extraction with a combination of primary secondary amine (PSA, 50 mg),
      graphitized carbon black (GCB, 25 mg), and anhydrous sodium sulfate (150 mg); and
      final estimation by LC-MS/MS with multiple reaction monitoring. Direct analysis
      (no clean up) resulted in significant suppression in ionization of the majority
      of the test compounds over the electrospray ionization probe. However, clean up
      with the above combination of PSA + GCB reduced the matrix-induced signal
      suppressions significantly, and the signals in the cleaned extracts were nearly
      equivalent to the corresponding solvent standards. Substitution of PSA with
      florisil also gave equivalent clean up effects. The method was quite rugged as
      evident from a low Horwitz ratio (mostly <0.5) and low measurement uncertainties
      at 10 ng g(-1). The limit of quantification was <10 ng g(-1) for all of the
      pesticides with recoveries within 70-120% for most pesticides even at 2.5 ng g(
      1). The method offers a significantly effective, sensitive, cheaper, and safer
      alternative to the existing methods of multiresidue analysis.

PMID- 19378944
TI  - Effect of Chokeberry (Aronia melanocarpa) juice on the metabolic activation and
      detoxication of carcinogenic N-nitrosodiethylamine in rat liver.
AB  - Chokeberry is a rich source of polyphenols, which may counteract the action of
      chemical carcinogens. The aim of this study was to examine the effect of
      chokeberry juice alone or in combination with N-nitrosodiethylamine (NDEA) on
      phase I and phase II enzymes and DNA damage in rat liver. The forced feeding with
      chokeberry juice alone decreased the activities of enzymatic markers of
      cytochrome P450, CYP1A1 and 1A2. NDEA treatment also decreased the activity of
      CYP2E1 but enhanced the activity of CYP2B. Pretreatment with chokeberry juice
      further reduced the activity of these enzymes. Modulation of P450 enzyme
      activities was accompanied by the changes in the relevant proteins levels. Phase
      II enzymes were increased in all groups of animals tested. Chokeberry juice
      augmented DNA damage and aggravated the effect of NDEA. These results indicate
      that chokeberry may protect against liver damage; however, in combination with
      chemical carcinogens it might enhance their effect.

PMID- 19378945
TI  - Lipoxygenase activity is involved in the regeneration of volatile ester
      synthesizing capacity after ultra-low oxygen storage of 'Fuji' apple.
AB  - An extra period under cold air after ultra-low oxygen storage has been shown to
      increase the concentration of some volatile compounds emitted by stored 'Fuji'
      apples. The purpose of this work was to assess the role, if any, of lipoxygenase
      and hydroperoxide lyase activities in the regeneration of fruit capacity for
      volatile production after ultra-low oxygen storage. Fruits were stored at 1 
      degrees C and 92% relative humidity under ultra-low oxygen (1 kPa of O2/1 kPa of
      CO2); one lot was kept under hypoxia for 19 or 30 weeks, a second lot was
      maintained for 17 or 28 weeks under these conditions and then stored for 2 weeks
      in cold air, and a third lot remained for either 15 or 26 weeks under ultra-low
      oxygen followed by 4 weeks under cold air. Samples were placed subsequently at 20
      degrees C, and analyses of volatile emission and enzyme activities were
      undertaken 1 and 7 days thereafter. Fruit stored during 4 weeks in cold air after
      ultra-low oxygen storage showed the highest capacity for volatile regeneration.
      Higher emission of volatiles by these samples was concomitant with higher levels
      of lipoxygenase activity. Results suggest that lipoxygenase activity,
      particularly in the flesh tissue, was strongly related to the regeneration of the
      emission of volatile compounds allowed by the extra period in cold air after
      ultra-low oxygen storage and, thus, appears to be a key control point for
      successful recovery of fruit ability for volatile compound production.

PMID- 19378946
TI  - Yam storage protein dioscorins from Dioscorea alata and Dioscorea japonica
      exhibit distinct immunomodulatory activities in mice.
AB  - The aim of this study was to elucidate the effect of the major storage protein
      dioscorin isolated from two different yam species, Tainong No. 1 (TN1-dioscorins)
      and Japanese yam (Dj-dioscorins), on the immune activities of mice. Dj
      dioscorins, like TN1-dioscorins, could induce expression of the pro-inflammatory
      cytokines and stimulate phagocytosis of RAW 264.7. Intraperitoneal injection of
      the TN1-dioscorins into mice stimulated phagocytosis of bone marrow, spleen, and
      thymic cells. In contrast, the T and B cells in bone marrow, spleen, and thymus
      isolated from mice injected with Dj-dioscorins had higher proliferative responses
      to mitogens. Furthermore, Dj-dioscorins enhanced proliferation of CD4(+), CD8(+),
      and Tim3(+) (Th1) cells in spleen and CD19(+) cells in both spleen and thymus.
      Supplement of Dj-dioscorins in the lymphoid cells isolated from Dj-dioscorins
      primed mice induced cell proliferation of both spleen and thymic cells. These
      findings indicated that TN1-dioscorins have a higher ability to stimulate the
      phagocytic activity of the lymphoid cells than Dj-dioscorins, whereas Dj
      dioscorins possess more abilities than TN1-dioscorins to enhance the
      proliferation of the lymphoid cells.

PMID- 19378949
TI  - Capturing and analyzing the excited-state structure of a Cu(I) phenanthroline
      complex by time-resolved diffraction and theoretical calculations.
AB  - Time-resolved crystallography and density functional theory calculations are used
      to analyze the geometric and electronic changes that occur upon photoexcitation
      of [Cu(I)(dmp)(dppe)](+) in crystalline [Cu(I)(dmp)(dppe)][PF(6)] [dmp = 2,9
      dimethyl-1,10-phenanthroline; dppe = 1,2-bis(diphenylphosphino)ethane]. In the
      pump-probe experiment, laser and X-ray pulses are synchronized to capture an
      image of the instantaneous molecular distortions in the transient triplet state.
      Parallel theoretical calculations, with the phenyl groups replaced by methyl
      groups, yield information on the distortion of the isolated cation and the change
      in electron density upon excitation. The experimental distortions are
      significantly less than the calculated values and are different for the two
      independent molecules in the asymmetric unit; these findings are attributed to
      the constraining influence of the crystal matrix. The calculations indicate that
      the electron transfer upon excitation is mostly from the dmpe ligand to the dmp
      ligand, while the Cu atomic charge changes by only approximately +0.1e, although
      the charge distribution on Cu is significantly affected. As found for homoleptic
      [Cu(I)(dmp)(2)](+), the change in the population of the Cu atom is close to the
      calculated difference between the corresponding Cu(II) and Cu(I) complexes.
      Charge density difference maps confirm these conclusions and show a large
      rearrangement of the electron density on the Cu atom upon excitation.

PMID- 19378948
TI  - NMR analysis of the architecture and functional remodeling of a modular
      multidomain protein, RPA.
AB  - Modular proteins with multiple domains tethered by flexible linkers have variable
      global architectures. Using the eukaryotic ssDNA binding protein, Replication
      Protein A (RPA), we demonstrate that NMR spectroscopy is a powerful tool to
      characterize the remodeling of architecture in different functional states. The
      first direct evidence is obtained for the remodeling of RPA upon binding ssDNA,
      including an alteration in the availability of the RPA32N domain that may help
      explain its damage-dependent phosphorylation.

PMID- 19378950
TI  - Unusual interchromophoric interactions in beta,beta' directly and doubly linked
      corrole dimers: prohibited electronic communication and abnormal singlet ground
      states.
AB  - Directly and doubly beta,beta'-linked corrole dimers (DH(3)CD, DH(2)CD, and
      DZnCD) are excellent platforms for the investigation of intercorrole interactions
      because of their enforced coplanar geometries and short edge-to-edge distances.
      Through the use of these molecules along with the reference monomer H(3)CM and
      the singly beta,beta'-linked corrole dimer SH(3)CD, the intercorrole interactions
      have been systematically studied by density functional theory calculations,
      ultrafast photophysical measurements, and two-photon absorption measurements. A
      particular focus was placed on revealing factors that are important for the
      induced photophysical properties of the doubly linked corrole dimers compared
      with corrole monomer. In the doubly linked corrole dimers, strong molecular
      orbital interactions caused by the coplanar geometry and the short
      interchromophoric distance give rise to perturbations of the electronic states
      that are responsible for the red-shifted and intensified Q-like band in DH(3)CD
      and the broad NIR absorption bands and fast excitation-energy relaxation
      processes in DH(2)CD and DZnCD. On the other hand, electronic communication
      between corrole units is prohibited by the structurally constrained octagonal
      core in the center, so each constituent corrole unit in the doubly linked corrole
      dimers maintains an intrinsic pi-conjugation system. Consequently, the overall
      aromaticity of the directly linked corrole dimers can be explained in terms of a
      linear sum of two constituent corrole monomers, and the singlet biradical
      character of DH(2)CD and DZnCD can be understood in terms of two unpaired
      electrons (one from each constituent oxidized corrole monomer) and their
      appropriate interaction. In addition, the nonlinear optical properties of DH(2)CD
      and DZnCD with singlet biradical character have been confirmed to be
      significantly enhanced compared with those of closed-shell DH(3)CD. Collectively,
      double beta,beta'-linkages of corroles provide the coplanar geometry with a short
      interchromophoric distance and the strained octagonal core that play key roles in
      allowing the strong molecular orbital interactions and restricting the electronic
      communication between the two corroles, respectively.

PMID- 19378951
TI  - Quadruply bonded dimetal units supported by 2,4,6-triisopropylbenzoates
      MM(TiPB)(4) (MM = Mo(2), MoW, and W(2)): preparation and photophysical
      properties.
AB  - The preparation and characterization (elemental analysis, (1)H NMR, and cyclic
      voltammetry) of the new compounds MM(TiPB)(4), where MM = MoW and W(2) and TiPB =
      2,4,6-triisopropylbenzoate, are reported. Together with Mo(2)(TiPB)(4),
      previously reported by Cotton et al. (Inorg. Chem. 2002, 41, 1639), the new
      compounds have been studied by electronic absorption, steady-state emission, and
      transient absorption spectroscopy (femtosecond and nanosecond). The compounds
      show strong absorptions in the visible region of the spectrum that are assigned
      to MMdelta to arylcarboxylate pi* transitions, (1)MLCT. Each compound also shows
      luminescence from two excited states, assigned as the (1)MLCT and
      (3)MMdeltadelta* states. The energy of the emission from the (1)MLCT state
      follows the energy ordering MM = Mo(2) > MoW > W(2), but the emission from the
      (3)MMdeltadelta* state follows the inverse order: MM = W(2) > MoW > Mo(2).
      Evidence is presented to support the view that the lower energy emission in each
      case arises from the (3)MMdeltadelta* state. Lifetimes of the (1)MLCT states in
      these systems are approximately 0.4-6 ps, whereas phosphorescence is dependent on
      the MM center: Mo(2) approximately 40 micros, MoW approximately 30 micros, and
      W(2) approximately 1 micros.

PMID- 19378952
TI  - Formation and reactivity of [(tacn)-N-CO-Re(III)Br(CO)(2)](+) in water: a
      theoretical and experimental study.
AB  - The chemistry of [(tacn)-N-CO-Re(III)(CO)(2)Br]X (X = Cl or Br), obtained in good
      yield from the reaction of fac-[(tacn)Re(I)(CO)(3)]Br (1, tacn = 1,4,7
      triazacyclononane) with X(2) in water, is described. The [(tacn)-N-CO
      Re(III)(CO)(2)Br]X complex (2 with X = Br(-); 2a with X = BrCl(2)(-)), which we
      have previously communicated, is characterized by an unusual three-membered ring
      acyl amide bond. Complex 2 is stable as a solid but is reactive in aqueous
      solution. Under basic conditions (1 M NaOH), reductive decarbonylation was
      observed, and the bis-carbonyl complex [(tacn)Re(I)(CO)(2)Br] (3) was obtained in
      quantitative yield. The Br(-) ligand in 3 could be replaced by CN(-), giving the
      neutral complex [(tacn)Re(I)(CO)(2)(CN)] (4). In acidic media (1 M HBr), complex
      2 partially converted to the monocarbonyl mu-oxo bridged dinuclear complex
      {[(tacn)Re(III)(CO)Br](2)O}(2+) (5 as [PF(6)](-) salt). Under mild oxidative
      conditions the trioxo [(tacn)Re(VII)O(3)](ReO(4)(-)) (6) was formed almost
      quantitatively, and small amounts of the uncommon Re(VI) complex
      [(tacn)Re(VI)O(2)Br](ReO(4)(-)) (7) were identified. Mechanistic investigations
      at the density functional level of theory (DFT) showed that the elementary steps
      in the formation of 2 from 1 and 3 from 2 involved reactions of the complexes
      with hydroxide. The calculated pathway is strongly exothermic (ca. -137
      kcal/mol), confirming the energetically and kinetically highly favored formation
      of 3. The X-ray structures of 2a and 3-5 are reported and discussed.

PMID- 19378953
TI  - Vanadium octacyanoniobate-based magnet with a Curie temperature of 138 K.
AB  - In this work, we prepared a three-dimensional vanadium octacyanoniobate-based
      magnet, K(0.10)V(II)(0.54)V(III)(1.24)[Nb(IV)(CN)(8)].(SO(4))(0.45).6.8H(2)O.
      This compound exhibits ferrimagnetism with a Curie temperature of 138 K, in which
      the sublattice magnetizations of V(II) (S = (3)/(2)) and V(III) (S = 1) are
      antiparallelly ordered to that of Nb(IV) (S = (1)/(2)). The estimated
      superexchange interaction constants of V(II)-Nb(IV) and V(III)-Nb(IV) are -51 and
      -25 cm(-1), respectively.

PMID- 19378954
TI  - Humanin structural versatility and interaction with model cerebral cortex
      membranes.
AB  - Humanin (HN) is a recently identified neuroprotective peptide able to inhibit
      neurotoxicity induced by various insults which can be related to Alzheimer
      disease (AD) as well as to cell death induced by other stimuli. Previous CD and
      NMR studies demonstrated that HN adopts an unordered conformation in water, a
      alpha-helix conformation in 30% TFE, and a beta-sheet structure in PBS.
      Furthermore, other studies clearly indicated HN as a secreted peptide, able to
      prevent neuronal cell death caused by amyloid beta (Abeta) derivatives. Although
      Abeta was found to interact with neuronal membranes, currently there is not
      experimental evidence unveiling HN interaction with membranes. In this paper a
      spin labeling technique coupled with electron paramagnetic resonance (EPR) and
      circular dichroism (CD) has been used to study the structure and dynamics of HN
      in solution and for the first time in the presence of model cerebral cortex
      membranes (CCM). We have demonstrated that HN has a great tendency to aggregate
      even at low concentrations in water solutions at different ionic strengths and
      monomerizes in the TFE apolar environment. We also showed that HN slightly
      perturbs model CCM at the surface assuming a clear beta-sheet conformation. In
      addition, HN increases the fluidity of the bilayer core without penetrating into
      the membrane.

PMID- 19378955
TI  - Effective transition probability for the Faraday effect of lanthanide(III) ion
      solutions.
AB  - The Faraday effects of 14 lanthanide(III) ion solutions were systematically
      analyzed on the basis of the Faraday C term. The effective transition
      probability, K, which measures the magneto-optical contribution of the 4f(n) -->
      4f(n-1)5d transition to the molar Verdet constant, was determined. Linear
      correlations between K and the square root of the molar magnetic susceptibility
      of the lanthanide(III) ions, chi(m)(1/2), were obtained. From the observed new
      regularity, K for promethium(III) was estimated.

PMID- 19378957
TI  - Systems biological responses to chronic perfluorododecanoic acid exposure by
      integrated metabonomic and transcriptomic studies.
AB  - Perfluorocarboxylic acids (PFCAs) have been widely used in consumer and
      industrial products, such as food packaging, and found in the blood of both
      humans and wildlife. Although studies showed a high tendency toward biological
      accumulation and a variety of toxic effects for PFCAs, the mechanistic aspects of
      their toxicity remain unknown. In present study, we investigated the dosage
      dependent metabonomic and transcriptomic responses of male rats to the exposure
      to perfluorododecanoic acid (PFDoA) over 110 days. Our NMR-based metabonomics
      results for both liver tissues and serum demonstrated that PFDoA exposure led to
      hepatic lipidosis, which was characterized by a severe elevation in hepatic
      triglycerides and a decline in serum lipoprotein levels. The results from
      transcriptomic changes induced by PFDoA corroborated these results with changes
      in gene transcript levels associated with fatty acid homeostasis. These results
      demonstrate that PFDoA induces hepatic steatosis via perturbations to fatty acid
      uptake, lipogenesis, and fatty acid oxidation. Several serum metabolites
      exhibited dose-dependences, providing thorough descriptions of changes induced by
      PFDoA exposure. These observations yielded novel insights regarding the
      toxicological mechanism of PFCAs at the systems level.

PMID- 19378959
TI  - Modeling K+ and Ag+ complexation by thiacalix[4]arene amides using DFT: the role
      of intramolecular hydrogen bonding.
AB  - Complexation of methyl-glycine-amide functionalized thiacalix[4]arene with K(+)
      and Ag(+) has been studied using density functional theory (DFT) in the gas
      phase. To account for the conformational possibilities of the ligand, the free
      ligand and its potassium complexes were subjected to global minima searches on
      the molecular mechanics (MM) level of theory with the OPLS (optimized potentials
      for liquid simulations) force field. For the free ligand, the order of the
      energies and geometries of the ligand conformers is in agreement between MM and
      DFT; however, the position of K(+) in the ligand's cavity was predicted
      differently by these methods. Hydrogen bonding of amide hydrogens in the ligands'
      podand arms was found to take place predominantly with the ether oxygens of the
      same arm rather than the other arms' carbonyls. According to DFT calculations,
      the silver cation preferred to coordinate with one sulfur bridge and three
      carbonyl groups, whereas potassium cation favored interaction with the four
      carbonyl oxygens of the podand amide arms. Neither cation preferred the N-mode of
      coordination. For all obtained conformers, intramolecular hydrogen bonds disfavor
      complexation, increasing the preorganizational energy to be paid.

PMID- 19378958
TI  - DFT/TDDFT exploration of the potential energy surfaces of the ground state and
      excited states of Fe2(S2C3H6)(CO)6: a simple functional model of the [FeFe]
      hydrogenase active site.
AB  - Fe(2)(S(2)C(3)H(6))(CO)(6) (a) is a simple model of the [FeFe] hydrogenase
      catalytic site. The topology of the potential energy surface (PES) of this
      complex, of its cationic and anionic species (a(+) and a(-)), and of its lowest
      triplet state was studied using density functional theory (DFT) with BP86 and
      B3LYP functionals, while selected low- and high-lying singlet excited states were
      studied with the time-dependent density functional theory (TDDFT). The global
      minima of a and a(-) PESs are characterized by an all-terminal CO ligand
      arrangement, while the two rotated forms are transition states (TS). On the
      contrary, for the a(+) and lowest triplet state PES, the three forms considered
      are local minima, and the syn rotated form is the global minimum. The relative
      stability of the rotated forms and the all-terminal CO form on the a, a(+), and
      a(-) PESs is discussed in light of the Quantum Theory of Atoms in Molecules
      (QTAIM) analysis of the electron density. By comparing the Fe-Fe bond features of
      the three forms for each PES, we found that the global minimum structure is
      characterized by the shortest Fe-Fe bond distance and highest electron density at
      the Fe-Fe critical point. This approach gave evidence that in the a rotated
      forms, the weak Fe-C(mu) interaction between the Fe atom of the unrotated
      Fe(CO)(3) and the C atom of the semibridged CO is formed to the detriment of the
      Fe-Fe bond interaction. These results suggest that the stabilization of the
      rotated forms on the cationic PES might be due to the formation of the weak Fe
      C(mu) interaction minimizing the weakening of the Fe-Fe bond. The low-lying and
      lowest triplet excited-state PES investigated are characterized by the
      stabilization of the rotated forms over the all-terminal CO ligand arrangement.
      On the first singlet 1(1)A'' excited-state PES, an Fe(CO)(3) semirotated
      structure is the lowest-energy stationary point, while the exploration of the
      1(1)A' and 2(1)A'' singlet excited PESs evidences the stabilization of the
      rotated over the all-terminal CO forms. Singlet excited-state optimized geometry
      results are compared with excited-state nuclear distortions recently obtained
      from resonance Raman excitation profiles. Finally, the results of the exploration
      of the 6(1)A' and 9(1)A' high-lying excited PESs are discussed in light of the
      recent ultraviolet photolysis experiments on a.

PMID- 19378960
TI  - Characterization of multifunctional reverse micelles' interfaces using
      hemicyanines as molecular probes. II: Effect of the surfactant.
AB  - In this work, we have investigated the behavior of the cationic hemicyanine trans
      4-[4-(dimethylamino)-styryl]-N-methylpyridinium iodide (HC) in benzene/benzyl-n
      hexadecyl dimethylammonium chloride (BHDC)/water reverse micelle media using
      absorption and emission spectroscopy in addition to the steady-state and time
      resolved fluorescence emission techniques and compare the results to those
      obtained in benzene/sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT)/water reverse
      micelle media (Moyano, F.; et al. J. Phys. Chem. B 2009, 113, 4284.) in order to
      gain more insight about reverse micelle interface properties. Our results show
      that HC spectroscopic behavior is completely different when dissolved in AOT or
      in BHDC reverse micelle media. While the dye experiences an intramolecular charge
      transfer process upon excitation in the former media, in BHDC, this process is
      inhibited because of the cationic nature of the surfactant. Interestingly, we
      also show that the water properties are different for water molecules
      sequestrated inside of an anionic and cationic reverse micelle system. This come
      out because the water molecules entrapped inside of the BHDC reverse micelle
      media appear to be non-electron-donating because of its interaction with the
      cationic surfactant polar head group. On the other hand, the water molecules
      sequestrated inside of the AOT reverse micelle systems show its electron-donor
      ability enhanced in comparison with its water bulk structure. These results could
      also explain the lack of nucleophilicity shown by the water molecules entrapped
      in BHDC reverse micelle media reported in previous kinetic studies.

PMID- 19378961
TI  - Solvation of a spherical cavity in simple liquids: interpolating between the
      limits.
AB  - Dissolution of a solute molecule into a solvent necessitates the creation of a
      cavity devoid of solvent molecules. The cavity solvation free energy is exactly
      known at both very small and large length scales, but in between it can only be
      estimated by various approximations. Guided by simulation results for the
      solvation of small cavities and density functional theory, we analyze the size
      dependence of the solvation free energy, contact density of solvent molecules,
      and the interfacial tension for a spherical cavity in a Lennard-Jones fluid or a
      system of hard spheres. Unlike cavity formation in the hard-sphere system, a
      quadratic curvature expansion is insufficient to connect smoothly the exact
      results in the microscopic and macroscopic limits for the cavity surface tension
      (or equivalently, the contact solvent density) in Lennard-Jones fluids.
      Considering the sensitivity of solvation to molecular details at small length
      scales, we conjecture that, for practical purposes, a heuristic approach may be
      sufficient to link the thermodynamic limit at large length scales and the exact
      results of cavity formation at very small length scales.

PMID- 19378963
TI  - Cyanoesterification of 1,2-dienes catalyzed by nickel.
AB  - Cyanoformate esters add across 1,2-dienes in the presence of a nickel/PMe(2)Ph
      catalyst to afford beta-cyano-alpha-methylenealkanoates regioselectively, which
      are kinetically favored and readily isomerize to thermodynamically favored alpha
      cyanomethyl-alpha,beta-unsaturated carboxylates at high temperature under the
      nickel catalysis, possibly through oxidative addition of the C-CN bond. Similar
      cyanoesterification products are produced from chloroformate esters,
      trimethylsilyl cyanide, and 1,2-dienes in the presence of a nickel/dppp catalyst.
      The resulting cyanoesterification products have a structure of allylic cyanide
      and thus undergo further allyl cyanation reaction across alkynes with the aid of
      a nickel/P(4-CF(3)-C(6)H(4))(3) catalyst to afford highly substituted
      acrylonitrile derivatives.

PMID- 19378962
TI  - Computational methods for predicting sites of functionally important dynamics.
AB  - Understanding and controlling biological function of proteins at the atomic level
      is of great importance; allosteric mechanisms provide such an interface.
      Experimental and computational methods have been developed to search for residue
      mutations that produce changes in function by altering sites of correlated
      motion. These methods are often observational in that altered motions are
      achieved by random sampling without revealing the underlying mechanism(s). We
      present two deterministic methods founded on structure-function relationships
      that predict dynamic control sites (i.e., locations that experience correlated
      motions as a result of altered dynamics). The first method ("static") is based on
      a single structure conformation (e.g., the wild type (WT)) and utilizes a graph
      description of atomic connectivity. The local atomic interactions are used to
      compute the propagation of contact paths. This description of structure
      connectivity reveals flexible locations that are susceptible to altered dynamics.
      The second method ("dynamic") is a comparative analysis between the normal modes
      of a WT structure and a mutant structure. A mapping function is defined that
      quantifies the significance of the motions in one structure projected onto the
      motions of the other. Each mode is considered up- or down-regulated according to
      its change in relative significance. This description of altered dynamics is the
      basis for a motion correlation analysis, from which the dynamic control sites are
      readily identified. The methods are theoretically derived and applied using the
      canonical system dihydrofolate reductase (DHFR). Both methods demonstrate a very
      high predictive value (p<0.005) in identifying known dynamic control sites. The
      dynamic method also produces a new hypothesis regarding the mechanism by which
      the DHFR mutant achieves hyperactivity. These tools are suitable for allosteric
      investigations and may greatly enhance the speed and effectiveness of other
      computational and experimental methods.

PMID- 19378964
TI  - CuBr-catalyzed oxidative difluoromethylation of tertiary amines with difluoroenol
      silyl ethers.
AB  - CuBr-catalyzed oxidative difluoromethylation of readily available tertiary amines
      with difluoroenol silyl ethers was performed under mild conditions to afford beta
      amine-alpha,alpha-difluoro ketones.

PMID- 19378965
TI  - Aspects of structure and bonding in copper-amino acid complexes revealed by
      single-crystal EPR/ENDOR spectroscopy and density functional calculations.
AB  - This work deduces from a series of well-defined copper-doped amino acid crystals,
      relationships between structural features of the copper complexes, and ligand
      bound proton hyperfine parameters. These were established by combining results
      from electron paramagnetic resonance (EPR)/electron-nuclear double resonance
      (ENDOR) studies, crystallography, and were further assessed by quantum mechanical
      (QM) calculations. A detailed evaluation of previous studies on Cu(2+) doped into
      alpha-glycine, triglycine sulfate, alpha-glycylglycine, and L-alanine crystals
      reveal correlations between geometric features of the copper sites and proton
      hyperfine couplings from amino-bound and carbon-bound hydrogens. Experimental
      variations in proton isotropic hyperfine coupling values (a(iso)) could be fit to
      cosine-square dependences on dihedral angles, namely, for C(alpha)-bound
      hydrogens, a(iso) = -1.09 + 8.21 cos(2) theta MHz, and for amino hydrogens,
      a(iso) = -6.16 + 4.15 cos(2) phi MHz. For the C(alpha) hydrogens, this dependency
      suggests a hyperconjugative-like mechanism for transfer of spin density into the
      hydrogen 1s orbital. In the course of this work, it was also necessary to
      reanalyze the ENDOR measurements from Cu(2+)-doped alpha-glycine because the
      initial study determined the (14)N coupling parameters without holding its
      nuclear quadrupole tensor traceless. This new treatment of the data was needed to
      correctly align the (14)N hyperfine tensor principal directions in the molecular
      complex. To provide a theoretical basis for the coupling variations, QM
      calculations performed at the DFT level were used to compute the proton hyperfine
      tensors in the four crystal complexes as well as in a geometry-optimized
      Cu(2+)(glycine)(2) model. These theoretical calculations confirmed systematic
      changes in couplings with dihedral angles but greatly overestimated the
      experimental geometric sensitivity to the amino hydrogen isotropic coupling.

PMID- 19378966
TI  - Nonadiabatic molecular dynamics simulations of the energy transfer between
      building blocks in a phenylene ethynylene dendrimer.
AB  - The ultrafast dynamics of electronic and vibrational energy transfer between two-
      and three-ring linear poly(phenylene ethynylene) units linked by meta
      substitution is studied by nonadiabatic molecular dynamics simulations. The
      molecular dynamics with quantum transitions (1, 2) method is used including an
      "on the fly" calculation of the potential energy surfaces and electronic
      couplings. The results show that during the first 40 fs after a vertical
      photoexcitation to the S(2) state, the nonadiabatic coupling between S(2) and
      S(1) states causes a fast transfer of the electronic populations. A rapid
      decrease of the S(1)-S(2) energy gap is observed, reaching a first conical
      intersection at approximately 5 fs. Therefore, the first hopping events take
      place, and the S(2) state starts to depopulate. The analysis of the structural
      and energetic properties of the molecule during the jumps reveals the main role
      that the ethynylene triple bond plays in the unidirectional energy transfer
      process.

PMID- 19378967
TI  - Cleavage of [4Fe-4S]-type clusters: breaking the symmetry.
AB  - The cleavage of [4Fe-4S]-type clusters is thought to be important in proteins
      such as Fe-S scaffold proteins and nitrogenase. However, most [4Fe-4S](2+)
      clusters in proteins have two antiferromagnetically coupled high-spin layers in
      which a minority spin is delocalized in each layer, thus forming a symmetric
      Fe(2.5+)-Fe(2.5+) pair, and how cleavage occurs between the irons is puzzling
      because of the shared electron. Previously, we proposed a novel mechanism for the
      fission of a [4Fe-4S] core into two [2Fe-2S] cores in which the minority spin
      localizes on one iron, thus breaking the symmetry and creating a transition state
      with two Fe(3+)-Fe(2+) pairs. Cleavage first through the weak Fe(2+)-S bonds
      lowers the activation energy. Here, we propose a test of this mechanism: break
      the symmetry of the cluster by changing the ligands to promote spin localization,
      which should enhance reactivity. The cleavage reactions for the homoligand
      [Fe(4)S(4)L(4)](2-) (L = SCH(3), Cl, H) and heteroligand
      [Fe(4)S(4)(SCH(3))(2)L(2)](2-) (L = Cl, H) clusters in the gas phase were
      examined via broken-symmetry density functional theory calculations. In the
      heteroligand clusters, the minority spin localized on the iron coordinated by the
      weaker electron-donor ligand, and the reaction energy and activation barrier of
      the cleavage were lowered, which is in accord with our proposed mechanism and
      consistent with photoelectron spectroscopy and collision-induced dissociation
      experiments. These studies suggest that proteins requiring facile fission of
      their [4Fe-4S] cluster in their biological function might have spin-localized
      [4Fe-4S] clusters.

PMID- 19378968
TI  - Intermolecular ab initio potential and spectroscopy of the ground state of HeI2
      complex revisited.
AB  - The structure, energetics, and spectroscopy of ground-state HeI(2) molecule are
      analyzed from first principles. Ab initio methodology at CCSD(T) level of theory
      was employed, and large basis sets were used to compute the interaction energies.
      Scalar relativistic effects were accounted for by relativistic effective core
      potentials for the iodine atoms. Recent experimental investigations of the HeI(2)
      rovibronic spectra have estimated the ground-state binding energies of 16.6 +/-
      0.6 and 16.3 +/- 0.6 cm(-1) for the T-shaped and linear isomers, respectively.
      Given the extremely small difference between the two conformers, special
      attention was paid in the choice of basis sets used and the extrapolation schemes
      employed, as well as the fitting process for its analytical representation. The
      complete analytical form is provided, and variational fully quantum mechanical
      calculations were carried out by using the new parametrized surface, to evaluate
      vibrationally averaged structures and binding energies for the different
      conformers. The results obtained are in good accord with recent data available
      from experimental investigations of the He-I(2) rovibronic spectra.

PMID- 19378970
TI  - Stereoselective construction of seven-membered rings with an all-carbon
      quaternary center by direct Tiffeneau-Demjanov-type ring expansion.
AB  - Insertion of one methylene unit into the C-C bond of cyclohexanones is a
      potentially useful, straightforward method for the construction of seven-membered
      carbocycles. An especially appealing but largely unexplored method in this arena
      is the nucleophilic addition of diazoalkanes to the Lewis acid-activated
      cyclohexanones and subsequent ring expansion accompanied by the extrusion of
      nitrogen (direct Tiffeneau-Demjanov-type ring expansion). Our primary finding is
      the unprecedented insertion of alpha-alkyldiazoacetates to cyclohexanone and its
      heteroanalogues, generating seven-membered rings with one all-carbon quaternary
      center. On the basis of this finding, highly diastereoselective ring expansion of
      substituted cyclohexanones was developed, furnishing seven-membered rings with
      1,4-quaternary-tertiary, 1,4-quaternary-quaternary, or 1,3,5-quaternary-tertiary
      tertiary stereogenic centers in a single operation starting from readily
      available materials. The stereochemical outcome of the product can be easily
      predicted from the conformation of starting cyclohexanones. Enantioenriched
      products could be also accessed by the use of (-)-phenylmenthyl alpha
      alkyldiazoacetates.

PMID- 19378969
TI  - Water dynamics in salt solutions studied with ultrafast two-dimensional infrared
      (2D IR) vibrational echo spectroscopy.
AB  - Water is ubiquitous in nature, but it exists as pure water infrequently. From the
      ocean to biology, water molecules interact with a wide variety of dissolved
      species. Many of these species are charged. In the ocean, water interacts with
      dissolved salts. In biological systems, water interacts with dissolved salts as
      well as charged amino acids, the zwitterionic head groups of membranes, and other
      biological groups that carry charges. Water plays a central role in a vast number
      of chemical processes because of its dynamic hydrogen-bond network. A water
      molecule can form up to four hydrogen bonds in an approximately tetrahedral
      arrangement. These hydrogen bonds are continually being broken, and new bonds are
      being formed on a picosecond time scale. The ability of the hydrogen-bond network
      of water to rapidly reconfigure enables water to accommodate and facilitate
      chemical processes. Therefore, the influence of charged species on water hydrogen
      bond dynamics is important. Recent advances in ultrafast coherent infrared
      spectroscopy have greatly expanded our understanding of water dynamics. Two
      dimensional infrared (2D IR) vibrational echo spectroscopy is providing new
      observables that yield direct information on the fast dynamics of molecules in
      their ground electronic state under thermal equilibrium conditions. The 2D IR
      vibrational echoes are akin to 2D nuclear magnetic resonance (NMR) but operate on
      time scales that are many orders of magnitude shorter. In a 2D IR vibrational
      echo experiment (see the Conspectus figure), three IR pulses are tuned to the
      vibrational frequency of interest, which in this case is the frequency of the
      hydroxyl stretching mode of water. The first two pulses "label" the initial
      molecular structures by their vibrational frequencies. The system evolves between
      pulses two and three, and the third pulse stimulates the emission of the
      vibrational echo pulse, which is the signal. The vibrational echo pulse is
      heterodyne, detected by combining it with another pulse, the local oscillator.
      Heterodyne detection provides phase and amplitude information, which are both
      necessary to perform the two Fourier transforms that take the data from the time
      domain to a two-dimensional frequency domain spectrum. The time dependence of a
      series of 2D IR vibrational echo spectra provides direct information on system
      dynamics. Here, we use two types of 2D IR vibrational echo experiments to examine
      the influence that charged species have on water hydrogen-bond dynamics.
      Solutions of NaBr and NaBF(4) are studied. The NaBr solutions are studied as a
      function of the concentration using vibrational echo measurements of spectral
      diffusion and polarization-selective IR pump-probe measurements of orientational
      relaxation. Both types of measurements show the slowing of hydrogen-bond network
      structural evolution with an increasing salt concentration. NaBF(4) is studied
      using vibrational echo chemical-exchange spectroscopy. In these experiments, it
      is possible to directly observe the chemical exchange of water molecules
      switching their hydrogen-bond partners between BF(4)(-) and other water
      molecules. The results demonstrate that water interacting with ions has slower
      hydrogen-bond dynamics than pure water, but the slowing is a factor of 3 or 4
      rather than orders of magnitude.

PMID- 19378971
TI  - Recent applications of oxazoline-containing ligands in asymmetric catalysis.

PMID- 19378972
TI  - In vitro heavy-atom effect of palladium(II) and platinum(II) complexes of
      pyrrolidine-fused chlorin in photodynamic therapy.
AB  - Introduction of a heavy atom into photosensitizers generally facilitates
      intersystem crossing and improves the quantum yield (Phi(Delta)) of singlet
      oxygen ((1)O(2)), which is a key species in photodynamic therapy (PDT). However,
      little information is available about the physiological importance of this heavy
      atom effect. The aim of this study is to examine the heavy-atom effect in simple
      metallochlorins in vitro at the cellular level. 1,3-Dipolar cycloaddition of
      azomethine ylide to 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato
      palladium(II) and platinum(II) afforded metallochlorins 4b and 4c in yields of
      17.1 and 12.9%, respectively. The Phi(Delta) values increased in the order of 4a
      (0.28) < 4b (0.89) < 4c (0.92) in C(6)D(6). The photocytotoxicity of 4a, 4b, and
      4c was evaluated in HeLa cells at a light dose of 16 J x cm(-2) with lambda > 500
      nm and increased in the order of 4a < 4b < 4c at the concentration of 0.5 microM.
      The photocytotoxicity of 4b and 4c was significantly inhibited by addition of
      sodium azide, but not D-mannitol, suggesting that (1)O(2) is the major species
      causing cell death. Our results clearly indicate that 4b and 4c act as efficient
      (1)O(2) generators due to the heavy-atom effect in a cellular microenvironment as
      well as in nonphysiological media.

PMID- 19378974
TI  - First-principles study of the electronic structure and cluster formation in
      expanded liquid boron.
AB  - The electronic structure of liquid boron and cluster formation in expanded liquid
      boron have been investigated with first-principles molecular dynamics
      simulations. The calculated electronic density of states (DOS) exhibits a
      metallic feature, while liquid boron is known experimentally to be
      semiconductive. Since the DOS is not very sensitive to density, the electronic
      states near the Fermi level will consist mainly of dangling bonds, which explains
      the difference between the calculated and experimental results. Many types of
      clusters are formed in expanded liquid boron. This formation occurs in a very
      different way from that at low temperatures because expanded liquid boron has a
      high temperature and pressure that are close to the liquid-gas critical point. As
      the density is reduced, the coordination number in boron clusters decreases to
      about 2, indicating that the cluster geometry tends to be one- rather than two
      dimensional, which is the most stable form at low temperatures. In fact, the
      analysis of small clusters proved that one-dimensional forms are dominant over
      two- and three-dimensional forms. This is because one-dimensional geometries have
      a more flexible structure and a high entropy value that consequently reduces the
      free energy at high temperatures.

PMID- 19378973
TI  - Membrane-dependent interaction of factor Xa and prothrombin with factor Va in the
      prothrombinase complex.
AB  - Because all three protein components of prothrombinase, factors (f) Xa and Va and
      prothrombin, bind to negatively charged membrane phospholipids, the exact role of
      the membrane in the prothrombinase reaction has not been fully understood. In
      this study, we prepared deletion derivatives of fXa and prothrombin in which both
      the Gla and first EGF-like domains of the protease (E2-fXa) as well as the Gla
      and both kringle domains of the substrate (prethrombin-2) had been deleted. The
      fVa-mediated catalytic activity of E2-fXa toward prethrombin-2 was analyzed in
      both the absence and presence of phospholipids composed of 80%
      phosphatidylcholine (PC) and 20% phosphatidylserine (PS). PCPS markedly
      accelerated the initial rate of prethrombin-2 activation by E2-fXa, with the
      cofactor exhibiting saturation only in the presence of phospholipids (apparent
      K(d) of approximately 60 nM). Competitive kinetic studies in the presence of the
      two exosite-1-specific ligands Tyr(63)-sulfated hirudin(54-65) and TM456
      suggested that while both peptides are highly effective inhibitors of the fVa
      mediated activation of prethrombin-2 by E2-fXa in the absence of PCPS, they are
      ineffective competitors in the presence of phospholipids. Since neither E2-fXa
      nor prethrombin-2 can interact with membranes, these results suggest that
      interaction of fVa with PCPS improves the affinity of the activation complex for
      proexosite-1 of the substrate. Direct binding studies employing OG(488)-EGR
      labeled fXa and E2-fXa revealed that the interaction of the Gla domain of fXa
      with PCPS also induces conformational changes in the protease to facilitate its
      high-affinity interaction with fVa.

PMID- 19378975
TI  - Observation of "ionic lock" formation in molecular dynamics simulations of wild
      type beta 1 and beta 2 adrenergic receptors.
AB  - G protein coupled receptors (GPCRs) are a large family of integral membrane
      proteins involved in signal transduction pathways, making them appealing drug
      targets for a wide spectrum of diseases. The recently crystallized structures of
      two engineered adrenergic receptors have opened new avenues for the understanding
      of the molecular mechanisms of action of GPCRs. Taking the two crystal structures
      as a starting point, we carried out submicrosecond molecular dynamics simulations
      of wild-type beta(1) and beta(2) adrenergic receptors in a lipid bilayer under
      physiological conditions. These simulations give access to structural and dynamic
      properties of the receptors in pseudo in vivo conditions. For both systems the
      overall fold properties of the transmembrane region as well as the binding pocket
      remain close to the crystal structure of the engineered systems, thus suggesting
      that the ligand binding mode is not affected by the introduced modifications.
      Both simulations indicate the presence of one or two internal water molecules
      absent in both crystal structures and essential for the stabilization of the
      binding pocket at the interface between transmembrane helices III, IV, and V. The
      different interactions arising from the substitution of Tyr308 in beta(2)AR into
      Phe325 in beta(1)AR induce different conformations of the homologous Asn(6.55)
      inside the binding pockets of the two receptors, suggesting a possible origin of
      receptor specificity in agonist binding. The equilibrated structures of both
      receptors recover all of the previously suggested features of inactive GPCRs
      including formation of a salt bridge between the cytoplasmatic moieties of
      helices III and VI ("ionic lock") that is absent in the crystal structures.

PMID- 19378976
TI  - Nature of PO bonds in phosphates.
AB  - Making use of a combination of ab initio calculated geometries, orbital energies,
      and orbital spatial distributions as well as experimental information about bond
      lengths, bond energies, vibrational frequencies, and dipole moments, the nature
      of the terminal PO bond in phosphates such as (MeO)(3)PO was probed and compared
      to the case in MeO-P=O where P is trivalent and a PO pi bond is thus assumed to
      exist. We find that the MeO-P and terminal PO bond lengths in (MeO)(3)PO are
      essentially the same as in MeO-P=O and the terminal PO lengths are substantially
      shorter than single P-OMe bond lengths. We also find that the HOMO orbital
      energies in the two compounds are within 0.1 eV of one another and that these
      orbitals have spatial characteristics much like one would expect of a bonding pi
      orbital connecting two atoms from different rows of the periodic table. Using
      this data, making a comparison to the more familiar bonding arising in N(2), CO,
      and BF, and taking note of the dipole moments in compounds known to possess
      dative bonds, we conclude that it is best to represent the terminal PO bond in
      phosphates in terms of valence-bond structures such as (MeO)(3)P=O in which the
      formal charges are P(0)O(0) and where a single PO pi bond exists. However, when
      it comes to characterizing the PO antibonding pi* orbitals, significant
      differences arise. Electronic structure methods were able to identify the pi*
      orbital of MeO-P=O and to determine its energy (the MeO-P=O(-) anion is even
      bound). Similar attempts to identify the PO pi* orbital in the unbound
      (MeO)(3)P=O(-) anion lead us to conclude that this anion state is probably so
      strongly coupled to the continuum (i.e., to states corresponding to (MeO)(3)P=O
      plus a free electron) that it is so short lived as to be undetectable in
      experiments.

PMID- 19378977
TI  - Asymmetric kinetics of protein structural changes.
AB  - Thermodynamic and kinetic understanding of structural transformations in proteins
      is critical to new developments in medicine and biotechnology. These fields often
      require the design of mechanism-based modulators of protein function. Researchers
      increasingly consider these structural changes-such as folding/unfolding or
      shuttling between active and inactive states-within the energy landscape concept
      that supposes a high-dimensional, rugged conformational surface. The unevenness,
      or asperity, of this conformational surface results from energetic barriers and
      kinetic traps. However, for a large number of protein reactions, such as
      reversible folding/unfolding, the literature only reports simple two-state
      transitions, which calls into question the use of a more complex energy landscape
      model. The question is: are these reactions really that simple, or are we misled
      by a biased experimental approach? In this Account, we argue in favor of the
      latter possibility. Indeed, the frequently employed temperature-jump method only
      allows recording protein structure changes in the heating direction. Under those
      conditions, it might not be possible to detect other kinetic pathways that could
      have been taken in the cooling direction. Recently, however, we have developed
      bidirectional pressure- and temperature-jump methods, which can offer new
      insights. Here, we show the potential of these methods both for studying protein
      folding/unfolding reactions, taking ribonuclease A as model, and for studying
      functionally relevant protein conformational changes, using the open/closed
      allosteric transition of tryptophan synthase. For example, the heating and
      cooling temperature-jump induced kinetics involved in the folding/unfolding
      conformational surface of ribonuclease A is illustrated above. In both of our
      model systems, the kinetic transition states of several reaction steps were path
      dependent, i.e. the rates and thermodynamic activation parameters depend on the
      direction of the applied pressure and temperature perturbation. This asymmetry
      suggests that proteins cope with external stress by adapting their structure to
      form different ensembles of conformational substates. These states are
      distinguished by their activation enthalpy and entropy barriers, which can be
      strongly negative in the folding direction. Based on our analysis of activation
      compressibility and heat capacity, hydration and packing defects of the kinetic
      transition states are also very important for determining the reaction path. We
      expect that a more generalized use of this experimental approach should allow
      researchers to obtain greater insight into the mechanisms of physiologically
      relevant protein structural changes.

PMID- 19378978
TI  - Synthesis and photocytotoxicity of S-glucosylated 5,10,15,20
      Tetrakis(tetrafluorophenyl)porphyrin metal complexes as efficient (1)O(2)
      generating glycoconjugates.
AB  - 5,10,15,20-Tetrakis(4-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosylthio)-2,3,5,6
      tetrafluorophenyl)porphyrin 2a and its Zn(II), Pd(II), and Pt(II) complexes 2b,
      2c, and 2d were prepared in excellent yields by nucleophilic substitution of the
      corresponding free-base porphyrin and metalloporphyrins with acetyl 2,3,4,6-tetra
      O-acetyl-1-thio-beta-d-glucopyranoside. Deprotection of 2a, 2b, 2c, and 2d by
      alkaline hydrolysis afforded the corresponding S-glucosylated porphyrin 3a and
      its metal complexes 3b, 3c, and 3d. The structures and purity of all new
      photosensitizers were confirmed by elemental analysis and (1)H, (13)C, and (19)F
      NMR, UV-vis, and steady-state luminescence spectroscopy. The relative efficiency
      of singlet oxygen ((1)O(2)) production increased in the order of free-base
      fluoroporphyrins (2a and 3a) < Zn(II) complexes (2b and 3b) < Pd(II) complexes
      (2c and 3c), which can be explained in terms of the heavy-atom effect, while the
      (1)O(2)-producing efficiency of Pt(II) complexes (2d and 3d) were exceptionally
      low. In vitro photocytotoxicity of these eight S-glucosylated photosensitizers
      was examined in HeLa cells. Although all protected photosensitizers 2a, 2b, 2c,
      and 2d showed no photocytotoxicity, the photosensitizers 3a, 3b, and 3c exerted
      potent photocytotoxicity. These results clearly indicated that the sugar moieties
      of 3a, 3b, and 3c act as not only water-solubility-enhancing functionalities but
      also cellular-uptake-enhancing elements. Photocytotoxicity testing of 3a, 3b, and
      3c in the presence of reactive oxygen species inhibitors suggested that (1)O(2)
      is the major mediator of cell death. Hence, the Zn(II) and Pd(II) complexes 3b
      and 3c are promising photosensitizers having cellular uptake-facilitating units
      (sugar moieties) and enhanced (1)O(2) generation due to the heavy-atom effect.

PMID- 19378979
TI  - Charge-transfer excitons at organic semiconductor surfaces and interfaces.
AB  - When a material of low dielectric constant is excited electronically from the
      absorption of a photon, the Coulomb attraction between the excited electron and
      the hole gives rise to an atomic H-like quasi-particle called an exciton. The
      bound electron-hole pair also forms across a material interface, such as the
      donor/acceptor interface in an organic heterojunction solar cell; the result is a
      charge-transfer (CT) exciton. On the basis of typical dielectric constants of
      organic semiconductors and the sizes of conjugated molecules, one can estimate
      that the binding energy of a CT exciton across a donor/acceptor interface is 1
      order of magnitude greater than k(B)T at room temperature (k(B) is the Boltzmann
      constant and T is the temperature). How can the electron-hole pair escape this
      Coulomb trap in a successful photovoltaic device? To answer this question, we use
      a crystalline pentacene thin film as a model system and the ubiquitous image band
      on the surface as the electron acceptor. We observe, in time-resolved two-photon
      photoemission, a series of CT excitons with binding energies < or = 0.5 eV below
      the image band minimum. These CT excitons are essential solutions to the atomic H
      like Schrodinger equation with cylindrical symmetry. They are characterized by
      principal and angular momentum quantum numbers. The binding energy of the lowest
      lying CT exciton with 1s character is more than 1 order of magnitude higher than
      k(B)T at room temperature. The CT(1s) exciton is essentially the so-called
      exciplex and has a very low probability of dissociation. We conclude that hot CT
      exciton states must be involved in charge separation in organic heterojunction
      solar cells because (1) in comparison to CT(1s), hot CT excitons are more weakly
      bound by the Coulomb potential and more easily dissociated, (2) density-of-states
      of these hot excitons increase with energy in the Coulomb potential, and (3)
      electronic coupling from a donor exciton to a hot CT exciton across the D/A
      interface can be higher than that to CT(1s) as expected from energy resonance
      arguments. We suggest a design principle in organic heterojunction solar cells:
      there must be strong electronic coupling between molecular excitons in the donor
      and hot CT excitons across the D/A interface.

PMID- 19378980
TI  - The Cl + H2 --> HCl + H reaction induced by IR + UV irradiation of Cl2 in solid
      para-H2: experiment.
AB  - We report IR + UV coirradiation photolysis experiments conducted on Cl(2)-doped
      para-hydrogen (p-H(2)) crystals at 1.8 K, using pulsed 355 nm UV radiation and cw
      broad-band near-IR light from a FTIR tungsten source. The amount of HCl
      photoproduct is monitored using FTIR spectroscopy as a function of the IR + UV
      exposure time. Detailed analysis of the HCl growth kinetics reveals that the
      reaction Cl + H(2)(v=1,J=0) --> HCl + H is playing a significant (15%) role in
      the in situ photochemistry. In contrast, UV-only photolysis experiments conducted
      under similar conditions produce almost exclusively (99%) isolated Cl atom
      photofragments, indicating the reaction Cl + H(2)(v=0,J=0) --> HCl + H is not
      readily occurring. This combination of photolysis experiments confirms that under
      these conditions, the Cl + H(2) reaction probability increases by a factor
      greater than 25 for Cl atom reactions with H(2)(v=1) versus H(2)(v=0). These
      results are therefore consistent with the expectation that vibrational excitation
      of the H(2) reagent lowers the reaction threshold and increases the reaction
      cross section for the Cl + H(2) reaction. These experimental studies were
      motivated by and are compared to the quantum model simulations reported by
      Korolkov, Manz, and Schild in the accompanying paper.

PMID- 19378981
TI  - The Cl + H2 --> HCl + H reaction induced by IR + UV irradiation of Cl2 in solid
      para-H2: quantum model simulation.
AB  - Recent experimental investigations by the group of D. T. Anderson (Kettwich, S.
      C.; Raston, P. L.; Anderson, D. T. J. Phys. Chem. A 2009, 113, DOI
      10.1021/jp811206a) show that the reaction Cl + H(2) --> HCl + H in the para-H(2)
      crystal can be induced by infrared (IR) + ultraviolet (UV) coirradiations causing
      vibrational pre-excitation of the molecular reactant, H(2)(v=1), and generation
      of the atomic reactant, Cl((2)P(3/2)), by near-resonant photodissociation of a
      matrix-isolated Cl(2) molecule in the C (1)Pi(u) state, respectively. The
      corresponding reaction probability P(v=1) for the reactants Cl + H(2)(v=1) is
      approximately 0.15; this is approximately 25 times larger than P(v=0) for Cl +
      H(2)(v=0) (as initiated by pure UV irradiation). We present a simple three-step
      quantum model which accounts for some important parts of the experimental results
      and allows predictions for other scenarios, for example, UV photodissociation of
      the Cl(2) molecule by a laser pulse. The first step, vibrational pre-excitation
      of H(2), yields the molecular initial state which is described using the Einstein
      model of the para-H(2) crystal. The second step, photodissociation of Cl(2),
      generates the Cl((2)P(3/2)) atom approaching H(2)(v=1). In the third step, Cl
      reacts with H(2)(v=1) much more efficiently than with H(2)(v=0) close to
      threshold. The ultrashort time domains (approximately 100 fs) of steps 2 plus 3
      support one- and then two-dimensional models of photodissociation of Cl(2) by
      short laser pulses and of the subsequent reaction of the system Cl-H-H embedded
      in frozen environments. The widths of the corresponding wave function describing
      the translational motion of the reactants is revealed as a significant parameter
      which is determined not only by the duration of the laser pulse but, even more
      importantly, by the width of the Gaussian-type distribution of the center of mass
      of the H(2) molecule in its Einstein cell. As a consequence, the resulting P(v)
      are quite robust versus variations of the UV pulse durations, allowing
      extrapolations to continuous wave irradiation. Quantum dynamics simulations of
      the reaction reveal that the experimental results are due to energetic and
      dynamical effects.

PMID- 19378982
TI  - Molecularly mediated processing and assembly of nanoparticles: exploring the
      interparticle interactions and structures.
AB  - The harnessing of the nanoscale properties of nanoparticles in most technological
      applications requires the abilities of controlled processing and assembly, which
      has been an important challenge because of the difficulty in manipulating
      interparticle properties. Molecularly mediated processing and assembly of
      nanoparticles have emerged as an important strategy for addressing this
      challenge. The capability of this strategy in manipulating size, shape,
      composition, and interparticle properties has significant implications for
      designing sensing, biosensing, nanoprobing, and many other functional
      nanostructures. This Account highlights some of the important findings in
      investigating both interparticle and collective properties as a forum for
      discussing new opportunities in exploiting nanoparticle-based designs and
      applications. The concept of mediator-template assembly of nanoparticles explores
      the combination of the forces from a mediator and a templating molecule for
      designing and controlling the interparticle interactions. The manipulation of the
      interparticle interaction properties and the detection of the molecular
      signatures are two of the key elements in this concept. A series of well-defined
      molecular mediators ranging from inorganic, organic, supramolecular, to
      biological molecules have been explored to ascertain how these two elements can
      be achieved in nanoparticle assemblies. The emphasis is the fundamental
      understanding of interparticle molecular interactions, such as covalent,
      electrostatic, hydrogen bonding, multidentate coordination, pi-pi interactions,
      etc. Each of these molecular interactions has been examined using specific
      molecules, such as multifunctional ligands, tunable sizes, shapes, or charges,
      well-defined molecular rigidity and chirality, or spectroscopic signatures, such
      as fluorescence and Raman scattering. Examples included thiols, thioethers,
      carboxylic acids, fullerenes, dyes, homocysteines, cysteines, glutathiones,
      proteins, and DNAs as molecular mediators for the assembly of gold, alloy, and
      magnetic nanoparticles. The understanding of these systems provided insights into
      how the unique electrical, optical, magnetic, and spectroscopic properties of the
      nanoparticle assemblies can be exploited for potential applications. This Account
      also highlights a few examples in chemical sensing and bioprobing to illustrate
      the importance of interparticle interactions and structures in exploiting these
      properties. One example involves thin-film assemblies of metal nanoparticles as
      biomimetic ion channels or chemiresistor sensing arrays by exploiting the
      nanostructured ligand framework interactions. Other examples explore the surface
      enhanced Raman scattering signature as nanoprobes for the detection of protein
      binding or the enzyme-based cutting of interparticle DNAs. The detailed
      understanding of the design and control parameters in these and other systems
      should have a profound impact on the exploration of nanoparticles in a wide range
      of technological applications.

PMID- 19378983
TI  - Reaction force analysis of solvent effects in the addition of HCl to propene.
AB  - We have investigated computationally, via reaction force analyses, the addition
      of HCl to propene, both Markovnikov and anti-Markovnikov, in the gas phase and in
      chloroform solution. The calculations were carried out at the CCSD(T)/aug
      pVTZ//B3LYP/aug-cc-pVDZ level. A particular interest was in the magnitudes of the
      two components of the activation energies that are defined by the minimum of the
      reaction force for each process. The total activation energies for Markovnikov
      and anti-Markovnikov addition are found to be, respectively, 39.7 and 45.9
      kcal/mol in the gas phase and 27.1 and 34.9 kcal/mol in chloroform solution. In
      solution, the first portion of the reaction (prior to the reaction force minimum)
      involves substantial stretching of the H-Cl bond, which makes that contribution
      to the total activation energy greater than in the gas phase. However the second
      part of the activation is much less energy demanding in solution for both the
      Markovnikov and anti-Markovnikov additions. The overall preference for
      Markovnikov addition is due to the electrostatic potential of propene favoring
      the initial approach of the HCl hydrogen to the terminal carbon.

PMID- 19378984
TI  - Effect of nanoparticle and aggregate size on the relaxometric properties of MR
      contrast agents based on high quality magnetite nanoparticles.
AB  - Colloidal dispersions of monodispersed and high-crystalline magnetite
      nanoparticles have been used to establish a relationship between magnetic
      properties and magnetic resonance (MR) relaxometric parameters in vitro.
      Magnetite nanoparticles with diameters between 4 and 14 nm were synthesized by
      thermal decomposition of Fe(acac)3 in different organic solvents and transformed
      to hydrophilic by changing oleic acid for dimercaptosuccinic acid (DMSA). A final
      treatment in alkaline water was critical to make the suspension stable at pH 7
      with xi-potential values of -45 mV and hydrodynamic sizes as low as 50 nm.
      Samples showed superparamagnetic behavior at room temperature, which is an
      important parameter for biomedical applications. Susceptibility increased with
      both particle and aggregate size, and for particles larger than 9 nm, the
      aggregate size was the key factor controlling the susceptibility. Relaxivity
      values followed the same trend as the suspension susceptibilities, indicating
      that the aggregate size is an important factor above a certain particle size
      governing the proton relaxation times. The highest relaxivity value, r2=317 s(-1)
      mM(-1), much higher than those for commercial contrast agents with similar
      hydrodynamic size, was obtained for a suspension consisting of 9 nm particles and
      70 nm of hydrodynamic size, and it was assigned to the higher particle
      crystallinity in comparison to particles prepared by coprecipitation. Therefore,
      it can be concluded that in addition to the sample crystallinity, both particle
      size and aggregate size should be considered in order to explain the magnetic and
      relaxivity values of a suspension.

PMID- 19378985
TI  - Fully uncomplexed cyclodextrin in mixed systems of vesicle-cyclodextrin:
      solvolysis of benzoyl chlorides.
AB  - In this contribution the influence of beta-cyclodextrin (CD) on the behavior of
      aqueous systems containing vesicles of dipalmitoyl phosphatidyl choline (DPPC)
      has been studied by determining the kinetics of the solvolysis reaction of
      substituted benzoyl chlorides whose solvolysis reactivity entails a high
      sensitivity on media properties. The application of the pseudophase formalism
      allowed us to obtain the thermodynamic and kinetic coefficients characteristic of
      the reaction, which are essentially independent of the concentration of CD. We
      were able to determine the percentages of uncomplexed cyclodextrin in equilibrium
      with the vesicular system which were in all cases compatible with 100%. The
      obtained results led us to conclude that the properties of DPPC vesicles are not
      affected by the presence of CD in the medium and there is no type of interaction
      between the CD and the vesicular surfactant monomers and, therefore, all
      cyclodextrin is present in the mixed system as uncomplexed cyclodextrin.

PMID- 19378986
TI  - Isothermal titration calorimetry studies of neutral salt effects on the
      thermodynamics of micelle formation.
AB  - Isothermal titration calorimetry, ITC, was used to determine the enthalpy and
      heat capacity changes that accompany micelle formation of decyldimethylphosphine
      oxide, APO10, from 15-79 degrees C in the presence of representative neutral
      salts from the Hofmeister series. The solutions investigated were water, 0.2,
      0.5, and 1.0 NaCl, 0.5 M NaF, KCl, KI, guanidinium chloride (GuHCl) and mannitol,
      and 0.333 M Na2SO4. The heat capacity change at 25 degrees C (but not the cmc)
      and the parameter that describes the temperature dependence of the heat capacity
      change, B (cal/(mol K2)), appear to be correlated. Calculated values of the ion
      effects on micelle formation from a recent salt ion partitioning model (SPM) of
      Pegram and Record [J. Phys. Chem. B 2007, 111, 5411-5417] were quantitatively
      related to the experimental value of the solute free energy increment (SFEI). Use
      of this model requires a calculation of the solvent accessible area (ASA), which
      yields values for the extent of hydration of the micelle interior. An alternate
      method to determine the ASA based on the heat capacity change for micelle
      formation at 25 degrees C of APO8-12 yielded values for the number of buried
      carbon atoms (5-12) versus previous estimates (4-8) from analysis of the B
      parameter.

PMID- 19378987
TI  - Microcalorimetric studies on chemical oscillation of microgels.
AB  - By use of isothermal titration calorimetry (ITC) and ultrasensitive differential
      scanning calorimetry (US-DSC), we have investigated the energy change in the
      periodic swelling-to-deswelling of thermally sensitive poly(N
      isopropylacrylamide) (PNIPAM) microgels containing ruthenium(II) tris(2,2'
      bipyridine) (Ru(bpy)3) which is a catalyst for Belousov-Zhabotinsky (BZ)
      reaction. As temperature increases, the induction period and oscillation period
      of BZ reaction decrease because the reaction rate increases. However, the
      oscillation disappears at a temperature above the lower critical solution
      temperature (LCST) of the microgels since Ru(bpy)3 is trapped in the microgels
      and cannot react with BZ substrates. As microgel size increases or the cross
      linking density decreases, the restriction of polymer networks on Ru(bpy)3
      decreases, so that Ru(bpy)3 can readily contact with BZ substrates, leading the
      oscillation amplitude to increase. In addition, the so-called transient chaos
      occurs at a low stirring speed, and it wanes with the increasing stirring speed.
      All the facts indicate that the contact between Ru(bpy)3 and BZ substrates
      determines the oscillation of the microgels.

PMID- 19378988
TI  - Probing ligand effects on the redox energies of [4Fe-4S] clusters using broken
      symmetry density functional theory.
AB  - A central issue in understanding redox properties of iron-sulfur proteins is
      determining the factors that tune the reduction potentials of the Fe-S clusters.
      Recently, Solomon and coworkers have shown that the Fe-S bond covalency of
      protein analogs measured by %L, the percent ligand character of the Fe 3d
      orbitals, from ligand K-edge X-ray absorption spectroscopy (XAS) correlates with
      the electrochemical redox potentials. Also, Wang and coworkers have measured
      electron detachment energies for iron-sulfur clusters without environmental
      perturbations by gas-phase photoelectron spectroscopy (PES). Here the
      correlations of the ligand character with redox energy and %L character are
      examined in [Fe(4)S(4)L(4)](2-) clusters with different ligands by broken
      symmetry density functional theory (BS-DFT) calculations using the B3LYP
      functional together with PES and XAS experimental results. These gas-phase
      studies assess ligand effects independently of environmental perturbations and
      thus provide essential information for computational studies of iron-sulfur
      proteins. The B3LYP oxidation energies agree well with PES data, and the %L
      character obtained from natural bond orbital analysis correlates with XAS values,
      although it systematically underestimates them because of basis set effects. The
      results show that stronger electron-donating terminal ligands increase %L(t), the
      percent ligand character from terminal ligands, but decrease %S(b), the percent
      ligand character from the bridging sulfurs. Because the oxidized orbital has
      significant Fe-L(t) antibonding character, the oxidation energy correlates well
      with %L(t). However, because the reduced orbital has varying contributions of
      both Fe-L(t) and Fe-S(b) antibonding character, the reduction energy does not
      correlate with either %L(t) or %S(b). Overall, BS-DFT calculations together with
      XAS and PES experiments can unravel the complex underlying factors in the redox
      energy and chemical bonding of the [4Fe-4S] clusters in iron-sulfur proteins.

PMID- 19378989
TI  - Synthesis and biological evaluation of 3,3-difluoropyridine-2,4(1H,3H)-dione and
      3-deaza-3-fluorouracil base and nucleoside derivatives.
AB  - New 3-deaza-3-halouracil nucleosides including 3-deaza-3-fluorouridine and its 2'
      deoxy and arabino analogues have been prepared by fluorination of protected
      precursors. The resulting 3,3-difluoropyridine-2,4(1H,3H)-dione derivatives
      underwent palladium-catalyzed hydrogenolysis of one C-F bond at atmospheric
      pressure, and deprotection gave the 3-deaza-3-fluorouracil compounds. Selective
      reaction of a stabilized Wittig reagent at C4 of the 3,3-difluoro-2,4-dione
      intermediates gave exocyclic alkenes that underwent hydrogenation accompanied by
      spontaneous elimination of hydrogen fluoride. Ammonolysis of the exocyclic
      carbethoxymethyl substituent and ester protecting groups gave 4
      (carboxamidomethyl)-3-deaza-3-fluorouridine and its analogues. Grignard additions
      at C4 of the ribo and 2'-deoxy 3,3-difluoro-2,4-dione intermediates followed by
      deprotection gave the 3-deaza-3,3-difluoro-4-hydroxy-4-(substituted)uracil
      nucleosides. The cytostatic activity of 3-fluoro-3-deazauridine (CC(50) = 4.4-9.6
      microM) in three cancer cell lines paralleled that of 3-deazauridine, whereas no
      significant inhibitory activity was observed with a variety of virus-infected
      cell cultures.

PMID- 19378990
TI  - Mapping adverse drug reactions in chemical space.
AB  - We present a novel method to better investigate adverse drug reactions in
      chemical space. By integrating data sources about adverse drug reactions of drugs
      with an established cheminformatics modeling method, we generate a data set that
      is then visualized with a systems biology tool. Thereby new insights into
      undesired drug effects are gained. In this work, we present a global analysis
      linking chemical features to adverse drug reactions.

PMID- 19378991
TI  - Chalcones: a valid scaffold for monoamine oxidases inhibitors.
AB  - A large series of substituted chalcones have been synthesized and tested in vitro
      for their ability to inhibit human monoamine oxidases A and B (hMAO-A and hMAO
      B). While all the compounds showed hMAO-B selective activity in the micro- and
      nanomolar ranges, the best results were obtained in the presence of chlorine and
      hydroxyl or methoxyl substituents. To better understand the enzyme-inhibitor
      interaction and to explain the selectivity of the most active compounds toward
      hMAO-B, molecular modeling studies were carried out on new, high resolution, hMAO
      B crystallographic structures. For the only compound that also showed activity
      against hMAO-A as well as low selectivity, the molecular modeling study was also
      performed on the hMAO-A crystallographic structure. The docking technique
      provided new insight on the inhibition mechanism and the rational drug design of
      more potent/selective hMAO inhibitors based on the chalcone scaffold.

PMID- 19378992
TI  - Gamma-aminobutyric acid amides of nortriptyline and fluoxetine display improved
      pain suppressing activity.
AB  - The GABA amides of the antidepressants nortriptyline and fluoxetine, 1 and 2,
      were compared to their respective parent compounds in rodent models of pain. The
      amides significantly reduced early nociceptive and late inflammatory responses
      compared to nortriptyline or fluoxetine, where 1 exhibited overall better
      efficacy than 2. Amide 1 was most efficacious in lowering cytokine secretion,
      edema and hyperalgesia induced by formalin and lambda-carrageenan, respectively.
      Thus, 1 is a promising candidate for the treatment of pain.

PMID- 19378993
TI  - First principles dynamics and minimum energy pathways for mechanochemical ring
      opening of cyclobutene.
AB  - We use ab initio steered molecular dynamics to investigate the mechanically
      induced ring opening of cyclobutene. We show that the dynamical results can be
      considered in terms of a force-modified potential energy surface (FMPES). We show
      how the minimal energy paths for the two possible competing conrotatory and
      disrotatory ring-opening reactions are affected by external force. We also locate
      minimal energy pathways in the presence of applied external force and show that
      the reactant, product, and transition state geometries are altered by the
      application of external force. The largest effects are on the transition state
      geometries and barrier heights. Our results provide a framework for future
      investigations of the role of external force on chemical reactivity.

PMID- 19378994
TI  - Si3C2-rings: from a nonconjugated trisilacyclopentadiene to an aromatic
      trisilacyclopentadienide and cyclic disilenide.
AB  - 1,2,3-Trisilacyclopenta-1,4-diene 2, featuring three skeletal Si atoms in the
      five-membered ring, was synthesized by the thermolysis of the 1,2,3
      trisilabicyclo[1.1.0]butane derivative 1 at 130 degrees C in the presence of hex
      3-yne. Possessing the properties of nonconjugated cyclopentadiene, 2 readily
      underwent reduction with KC(8), which was followed by treatment with LiBr to form
      the lithium salt of 1,2,3-trisilacyclopentadienide 3(-)*[Li(+)(thf)], from which
      the ketone-coordinated derivative 3(-)*[Li(+)(O=C(t)Bu(2))] was prepared. Both 3(
      )*[Li(+)(L)] (L = thf, O=C(t)Bu(2)) are classified as novel 6pi-electron aromatic
      systems based on their characteristic X-ray crystal and NMR spectral data.
      Addition of 12-crown-4 to 3(-)*[Li(+)(thf)] resulted in the unexpected formation
      of 4(-)*[Li(+)(12-crown-4)(2)], featuring the unprecedented cyclic disilenide ion
      4(-).

PMID- 19378995
TI  - Synthesis of methyl halides from biomass using engineered microbes.
AB  - Methyl halides are used as agricultural fumigants and are precursor molecules
      that can be catalytically converted to chemicals and fuels. Plants and
      microorganisms naturally produce methyl halides, but these organisms produce very
      low yields or are not amenable to industrial production. A single methyl halide
      transferase (MHT) enzyme transfers the methyl group from the ubiquitous
      metabolite S-adenoyl methionine (SAM) to a halide ion. Using a synthetic
      metagenomic approach, we chemically synthesized all 89 putative MHT genes from
      plants, fungi, bacteria, and unidentified organisms present in the NCBI sequence
      database. The set was screened in Escherichia coli to identify the rates of
      CH(3)Cl, CH(3)Br, and CH(3)I production, with 56% of the library active on
      chloride, 85% on bromide, and 69% on iodide. Expression of the highest activity
      MHT and subsequent engineering in Saccharomyces cerevisiae results in
      productivity of 190 mg/L-h from glucose and sucrose. Using a symbiotic co-culture
      of the engineered yeast and the cellulolytic bacterium Actinotalea fermentans, we
      are able to achieve methyl halide production from unprocessed switchgrass
      (Panicum virgatum), corn stover, sugar cane bagasse, and poplar (Populus sp.).
      These results demonstrate the potential of producing methyl halides from non-food
      agricultural resources.

PMID- 19378996
TI  - Mechanistic approach by which polysaccharides inhibit alpha-amylase/procyanidin
      aggregation.
AB  - The present work studies the inhibition of aggregation of alpha-amylase and
      procyanidin fractions by different polysaccharides (arabic gum, beta
      cyclodextrin, and pectins). Several analytical approaches, namely, fluorescence
      quenching, nephelometry, and dynamic light scattering (DLS), were used. In
      general, nephelometry showed that the presence of the polysaccharides in solution
      reduced the formation of insoluble aggregates. The fluorescence quenching
      measurements showed two effects: arabic gum and beta-cyclodextrin reduce the
      quenching effect of procyanidin fractions on alpha-amylase fluorescence, whereas
      pectins do not affect the quenching of alpha-amylase fluorescence by procyanidin
      fractions. DLS measurements have revealed that the polysaccharides studied induce
      a decrease in aggregates size, which probably is due to the formation of smaller
      aggregates resulting from the disruption and reorganization of the procyanidin
      fractions/alpha-amylase aggregates. Overall, the results obtained for arabic gum
      and beta-cyclodextrin strongly suggest that the main mechanism by which these two
      compounds inhibit protein/polyphenol aggregation is by molecular association
      between these polysaccharides and polyphenols, competing with protein
      aggregation. In the case of pectins, the results obtained provide evidence that
      the main mechanism by which they reduce protein/polyphenol aggregation is by
      forming a protein/polyphenol/polysaccharide complex, enhancing its solubility in
      aqueous medium.

PMID- 19378997
TI  - Regulation of lysozyme activity based on thermotolerant protein/smart polymer
      complex formation.
AB  - Proteins have evolved to acquire highly specialized biological functions and are
      ideal for various applications in both medicine and biotechnology, although
      denaturation is one of the major problems in protein chemistry. Here, we show a
      novel strategy for the regulation and preservation of the enzymatic activity even
      after heat treatment by the complex formation with a cationic smart copolymer,
      poly(N,N-diethylaminoethyl methacrylate)-graft-poly(ethylene glycol) (PEAMA-g
      PEG). PEAMA-g-PEG suppressed the enzymatic activity of lysozyme completely
      without any conformational change, indicating complex formation and the capping
      of the active site of lysozyme by PEAMA-g-PEG. The addition of an anionic
      polymer, poly(acrylic acid) (PAAc), recovered the inhibited enzymatic activity of
      the lysozyme/PEAMA-g-PEG complex completely. Surprisingly, even after heating the
      lysozyme with PEAMA-g-PEG for 20 min at 98 degrees C, the addition of PAAc
      recovered 80% enzymatic activity of lysozyme. Circular dichroism (CD) spectral
      analysis clearly indicated that the irreversible inactivation of lysozyme induced
      by the heat treatment was suppressed by the complex formation with PEAMA-g-PEG.

PMID- 19378998
TI  - Ligand-controlled access to [4 + 2] and [4 + 3] cycloadditions in gold-catalyzed
      reactions of allene-dienes.
AB  - By adjustment of the electronic properties of the ancilliary ligands, high
      selectivity can be achieved for either [4 + 2] or [4 + 3] cycloaddition reactions
      of allene-dienes catalyzed by gold(I). Triarylphosphitegold(I) complexes are
      employed as catalysts for a [4 + 2] cycloaddition reaction leading to
      alkylidenecyclohexenes. Conversely, di-tert-butylbiphenylphosphinegold(I)
      catalyzed reactions afford cycloheptadienes via [4 + 3] cycloaddition reactions.

PMID- 19378999
TI  - Imaging of mRNA in live cells using nucleic acid-templated reduction of
      azidorhodamine probes.
AB  - Nucleic acid-templated reactions leading to a fluorescent product represent an
      attractive strategy for the detection and imaging of cellular nucleic acids.
      Herein we report the use of a Staudinger reaction to promote the reduction of
      profluorescent azidorhodamine. The use of two cell-permeable GPNA probes, one
      labeled with the profluorescent azidorhodamine and the other with
      trialkylphosphine, enabled the detection of the mRNA encoding O-6-methylguanine
      DNA methyltransferase in intact cells.

PMID- 19379000
TI  - Nanomechanics of biocompatible hollow thin-shell polymer microspheres.
AB  - The nanomechanical properties of biocompatible thin-shell hollow polymer
      microspheres with approximately constant ratio of shell thickness to microsphere
      diameter were measured by nanocompression tests in aqueous conditions. These
      microspheres encapsulate an inert gas and are used as ultrasound contrast agents
      by releasing free microbubbles in the presence of an ultrasound field as a result
      of free gas leakage from the shell. The tests were performed using an atomic
      force microscope (AFM) employing the force-distance curve technique. An optical
      microscope, on which the AFM was mounted, was used to guide the positioning of
      tipless cantilevers on top of individual microspheres. We performed a systematic
      study using several cantilevers with spring constants varying from 0.08 to 2.3
      N/m on a population of microspheres with diameters from about 2 to 6 microm. The
      use of several cantilevers with various spring constants allowed a systematic
      study of the mechanical properties of the microsphere thin shell at different
      regimes of force and deformation. Using thin-shell mechanics theory for small
      deformations, the Young's modulus of the thin wall material was estimated and was
      shown to exhibit a strong size effect: it increased as the shell became thinner.
      The Young's modulus of thicker microsphere shells converged to the expected value
      for the macroscopic bulk material. For high applied forces, the force-deformation
      profiles showed a reversible and/or irreversible nonlinear behavior including
      "steps" and "jumps" which were attributed to mechanical instabilities such as
      buckling events.

PMID- 19379001
TI  - Preparation and gas adsorption studies of three mesh-adjustable molecular sieves
      with a common structure.
AB  - Solvothermal reactions of a predesigned amphiphilic ligand, 4'-tert-butyl
      biphenyl-3,5-dicarboxylate (BBPDC), with Zn(NO(3))(2), Co(NO(3))(2), and
      Cu(NO(3))(2) gave rise to three isostructural mesh-adjustable molecular sieves
      (MAMSs), MAMS-2, MAMS-3, and MAMS-4, respectively. The three new MAMSs all
      exhibit temperature-tuned molecular sieving effect. There exists a linear
      relationship between mesh size and temperature, D = D(0) + alphaT (D, mesh size
      at temperature T K; D(0), mesh size at 0 K; and alpha, constant). Constants D(0)
      and alpha are characteristics of a ligand in a certain structure, independent of
      the choice of metal. As a result, all of the three MAMSs based on the BBPDC
      ligand have a D(0) of 2.83 and an alpha of 0.0073.

PMID- 19379002
TI  - Nucleotide-promoted morphogenesis in amphiphile assemblies: kinetic control of
      micrometric helix formation.
AB  - Anionic nucleotides adenosine monophosphate or guanosine monophosphate interact
      with cationic vesicles, exchange with the counteranions of the amphiphiles in
      situ, and organize themselves at the membrane surfaces. Such organized
      nucleotides reciprocally transfer their chirality to membranes of nonchiral
      amphiphiles to induce the formation of right-handed micrometric helices on the
      time scale of hours. The kinetics of the nucleotide molecular organization and
      the formation of supramolecular helices was followed. We have shown that helix
      formation is a kinetic-dependent process that does not primarily result from ion
      exchange but from conformational reorganization and formation of weak
      interactions between confined nucleotides.

PMID- 19379003
TI  - Clavatadines C-E, guanidine alkaloids from the Australian sponge Suberea clavata.
AB  - Three new marine alkaloids, clavatadines C-E (1-3), together with the three known
      compounds aerophobin 1 (4), purealdin L (5), and aplysinamisine II (6) were
      isolated from extracts of the sponge Suberea clavata by bioassay-guided
      fractionation using a serine protease factor XIa assay. Their structures were
      determined by 1D and 2D NMR spectroscopy. Compounds 1-6 exhibited weak inhibition
      of factor XIa.

PMID- 19379004
TI  - Anisotropy of water droplets on single rectangular posts.
AB  - We report results of extensive experimental and numerical studies of the
      anisotropy of water drops deposited on single rectangular posts of mesoscopic
      size sculpted on different materials. Drops of different volume deposited on the
      top face of the posts assume an elongated shape along the post direction.
      Systematic investigations show that while the angle measured along the direction
      parallel to the post does not change, the one measured across them increases
      monotonically with the drop volume. The difference in these two angles is found
      to be proportional to the contact line eccentricity even for very elongated
      drops, regardless of the post size and material. Results obtained with the
      lattice Boltzmann method are consistent with these observations and indicate
      useful trends on the evolution of the drop shape with the system main parameters.
      We argue that drops deposited on single posts having a very sharp profile
      represent an ideal model system to investigate anisotropic wetting.

PMID- 19379005
TI  - Selective anodic desorption for assembly of different thiol monolayers on the
      individual electrodes of an array.
AB  - The close proximity of two individually addressable electrodes in an
      interdigitated array provides a unique platform for electrochemical study of
      multicatalytic processes. Here, we report a "plug-and-play" approach to control
      the underlying self-assembled monolayer and the electroactive species on each
      individually addressable electrode of an interdigitated array. The method
      presented here uses selective anodic desorption of a monolayer from one of the
      individually addressable electrodes and rapid formation of a different self
      assembled monolayer on the freshly cleaned electrode. We illustrate this strategy
      by introducing variations in the length of the linker to the electroactive
      species in the self-assembled monolayer, which determines the rate of electron
      transfer. In order to separate the assembly of the monolayer from the choice of
      the electroactive species, we use CuI-catalyzed triazole formation ("click"
      chemistry) to covalently attach an acetylene-terminated electroactive species to
      an azide-terminated thiol monolayer selectively on each electrode. The resulting
      variations in the electron-transfer rate to surface-attached ferrocene and in the
      rate of catalytic oxidation of ascorbate by the ferrocenium/ferrocene couple
      demonstrate an application of this approach.

PMID- 19379006
TI  - Water-soluble BODIPY derivatives.
AB  - New, water-soluble BODIPY dyes have been readily obtained from various BODIPY
      cores by reactions involving the introduction of novel sulfonated peptide chains
      by either coupling or substitution to give dimethylpropargylamine derivatives
      subsequently quaternized by reaction with propanesultone.

PMID- 19379007
TI  - Cu(I)-catalyzed intramolecular hydroamination of unactivated alkenes bearing a
      primary or secondary amino group in alcoholic solvents.
AB  - The Cu-Xantphos system [Cu(O-t-Bu)-Xantphos, 10-15 mol %] catalyzes the
      intramolecular hydroamination of unactivated terminal alkenes bearing an
      unprotected aminoalkyl substituent in alcoholic solvents, giving pyrrolidine and
      piperidine derivatives in excellent yields. This system is applicable to both
      primary and secondary amines and tolerates a variety of functional groups.

PMID- 19379008
TI  - Dynamic behaviors of droplet impact and spreading: water on five different
      substrates.
AB  - The dynamic wetting behaviors, especially the droplet morphology, of a water
      droplet impinging on five substrate surfaces were investigated. A water drop was
      released from 13.6 mm above a solid surface and impinged on substrates. The
      images (the silhouette and 45 degrees top view) were sequentially recorded from
      the moment that the droplet impacted the solid surface until it reached
      equilibrium. The entire profile of each of the water droplets during spreading
      was obtained from the digitized recorded images. The digitized droplets were then
      used to detail the spreading mechanism, including information on the relaxations
      of the wetting diameter, droplet height, contact angle, and spreading velocity. A
      comparison of the full droplet profiles allows us to clarify the independent
      motion of two related but independent components, the central region and rim, of
      an impinging droplet. An interesting plateau region in the droplet height
      relaxation curve was observed in the first cycle for all substrate surfaces. For
      hydrophobic surfaces (paraffin and Teflon), three particular growth modes in the
      droplet height relaxation curve were detected in every oscillation cycle during
      the early spreading stages. It only took three and four oscillation cycles for a
      water droplet on the glass and quartz substrates, respectively, to dissipate its
      energy and reach its equilibrium state. However, it took 72 and 28 oscillation
      cycles for a water droplet on the Teflon and paraffin substrates, respectively.
      Moreover, several other new phenomena were also observed.

PMID- 19379009
TI  - How to make the ionic Si-O bond more covalent and the Si-O-Si linkage a better
      acceptor for hydrogen bonding.
AB  - Variation of a bond angle can tune the reactivity of a chemical compound. To
      exemplify this concept, the nature of the siloxane linkage (Si-O-Si), the most
      abundant chemical bond in the earth's crust, was examined using theoretical
      calculations on the molecular model compounds H(3)SiOSiH(3), (H(3)Si)(2)OHOH, and
      (H(3)Si)(2)OHOSiH(3) and high-resolution synchrotron X-ray diffraction
      experiments on 5-dimethylhydroxysilyl-1,3-dihydro-1,1,3,3-tetramethyl-2,1,3
      benzoxadisilole (1), a molecular compound that gives rise to the formation of
      very rare intermolecular hydrogen bonds between the silanol groups and the
      siloxane linkages. For theoretical calculations and experiment, electronic
      descriptors were derived from a topological analysis of the electron density (ED)
      distribution and the electron localization function (ELF). The topological
      analysis of an experimentally obtained ELF is a newly developed methodology.
      These descriptors reveal that the Si-O bond character and the basicity of the
      siloxane linkage strongly depend on the Si-O-Si angle. While the ionic bond
      character is dominant for Si-O bonds, covalent bond contributions become more
      significant and the basicity increases when the Si-O-Si angle is reduced from
      linearity to values near the tetrahedral angle. Thus, the existence of the
      exceptional intermolecular hydrogen bond observed for 1 can be explained by its
      very small strained Si-O-Si angle that adopts nearly a tetrahedral angle.

PMID- 19379010
TI  - Purification and functional characterization of phiX174 lysis protein E.
AB  - Two classes of bacteriophages, the single-stranded DNA Microviridae and the
      single-stranded RNA Alloleviviridae, accomplish lysis by expressing "protein
      antibiotics", or polypeptides that inhibit cell wall biosynthesis. Previously, we
      have provided genetic and physiological evidence that E, a 91-amino acid membrane
      protein encoded by the prototype microvirus, varphiX174, is a specific inhibitor
      of the translocase MraY, an essential membrane-embedded enzyme that catalyzes the
      formation of the murein precursor, Lipid I, from UDP-N-acetylmuramic acid
      pentapeptide and the lipid carrier, undecaprenol phosphate. Here we report the
      first purification of E, which has been refractory to overexpression because of
      its lethality to Escherichia coli. Moreover, using a fluorescently labeled
      analogue of the sugar-nucleotide substrate, we demonstrate that E acts as a
      noncompetitive inhibitor of detergent-solubilized MraY, with respect to both
      soluble and lipid substrates. In addition, we show that the E sensitivity of five
      MraY mutant proteins, produced from alleles selected for resistance to E, can be
      correlated to the apparent affinities determined by in vivo multicopy suppression
      experiments. These results are inconsistent with previous reports that E
      inhibited membrane-embedded MraY but not the detergent-solubilized enzyme, which
      led to a model in which E functions by binding MraY and blocking the formation of
      an essential heteromultimeric complex involving MraY and other murein
      biosynthesis enzymes. We discuss a new model in which E binds to MraY at a site
      composed of the two transmembrane domains within which the E resistance mutations
      map and the fact that the result of this binding is a conformational change that
      inactivates the enzyme.

PMID- 19379011
TI  - Monitoring supported-nanocluster heterogeneous catalyst formation: product and
      kinetic evidence for a 2-step, nucleation and autocatalytic growth mechanism of
      Pt(0)n formation from H2PtCl6 on Al2O3 or TiO2.
AB  - A pressing problem in supported-metal-nanoparticle heterogeneous catalysis-
      despite the long history and considerable fundamental as well as industrial
      importance of such heterogeneous catalysts--is how to monitor such catalysts'
      formation more routinely, rapidly, and in real time. Such information is needed
      to better control the size, shape, composition, and thus resultant catalytic
      activity, selectivity, and lifetime of these important catalysts. To this end, a
      study is reported of the formation of supported Pt(0)(n) nanoparticles by H(2)
      reduction of H(2)PtCl(6) on Al(2)O(3) (or TiO(2)) to give 6 equivalents of HCl
      plus supported Pt(0)(n)/Al(2)O(3) (or Pt(0)(n)/TiO(2)), all while in contact with
      a solution of EtOH and cyclohexene. The HCl and Pt(0)(n) products were confirmed,
      respectively, by the stoichiometry of HCl formation using pH(apparent)
      measurements, appropriate standards, and by TEM and EDX measurements. The
      hypothesis of this research is that the kinetics of formation of this supported
      heterogeneous catalyst could be successfully monitored by a fast cyclohexene
      hydrogenation catalytic reporter reaction method first worked out for monitoring
      transition-metal nanoparticle formation in solution (Watzky, M. A. and Finke, R.
      G. J. Am. Chem. Soc. 1997, 119, 10382-10400). Significantly, sigmoidal kinetics
      of Pt(0)(n)/Al(2)O(3) catalyst formation were in fact successfully monitored by
      the catalytic hydrogenation reporter reaction method and then found to be well
      fit to the Finke-Watzky (hereafter F-W) 2-step, slow continuous nucleation and
      then autocatalytic surface growth mechanism, A --> B (rate constant k(1)) and A +
      B --> 2B (rate constant k(2)), respectively, in which A is the H(2)PtCl(6) and B
      is the growing, catalytically active Pt(0) nanoparticle surface. The finding that
      the F-W mechanism is applicable is significant in that it, in turn, suggests that
      the > or = 8 insights from studies of the mechanisms of soluble nanocluster
      formation can likely also be applied to supported heterogeneous catalyst
      synthesis, including a recent equation that gives nanocluster size vs time in
      terms of k(1), k(2), [A](o) and other parameters (Watzky, M. A., Finney, E. E.
      and Finke, R. G. J. Am. Chem. Soc. 2008, 130, 11959-11969 ). Also presented are
      the use of the catalytic reporter reaction to reveal H(2) gas to-solution mass
      transfer-limitations (MTL) in the system of H(2)PtCl(6) on TiO(2), results
      relevant to a recent communication in this journal. The use of the F-W 2-step
      nucleation and autocatalytic growth kinetic model to fit 3 literature examples of
      heterogeneous catalyst formation, involving H(2) reduction of both supported or
      bulk M(x)O(y) (i.e., and in gas-solid reactions), are also presented as part of
      the Supporting Information. A conclusion section is then provided summarizing the
      insights and caveats from the present work, as well as some needed future
      studies.

PMID- 19379012
TI  - Probing the structure and charge state of glutathione-capped Au25(SG)18 clusters
      by NMR and mass spectrometry.
AB  - Despite the recent crystallographic determination of the crystal structure of
      Au(25)(SCH(2)CH(2)Ph)(18) clusters, the question--whether all thiolate-capped, 25
      atom gold clusters adopt the same structure, regardless of the types of thiols
      (e.g., long-chain alkylthiols, aromatic thiols, or other functionalized ones)-
      still remains unanswered. To crystallize long-chain or bulky ligand (e.g.,
      glutathione)-capped Au(25)(SR)(18) clusters has proven to be difficult due to the
      major amorphousness caused by such ligands; therefore, one needs to seek other
      strategies to probe the structural information of such gold clusters. Herein, we
      report a strategy to probe the Au(25) core structure and surface thiolate ligand
      distribution by means of NMR in combination with mass spectrometry. We use
      glutathione-capped Au(25)(SG)(18) clusters as an example to demonstrate the
      utility of this strategy. One-dimensional (1D) and two-dimensional (2D)
      correlation NMR spectroscopic investigation of Au(25)(SG)(18) reveals fine
      spectral features that explicitly indicate two types of surface binding modes of
      thiolates, which is consistent with the ligand distribution in the
      Au(25)(SCH(2)CH(2)Ph)(18) cluster. Laser desorption ionization (LDI) mass
      spectrometry analysis shows that Au(25)(SG)(18) exhibits an identical ionization
      and core fragmentation pattern with phenylethylthiolate-capped Au(25) clusters.
      The charge state of the native Au(25)(SG)(18) clusters was determined to be -1 by
      comparing their optical spectrum with those of [Au(25)(SCH(2)CH(2)Ph)(18)](q) of
      different charge states (q = -1, 0). Taken together, our results led to the
      conclusion that glutathione-capped Au(25)(SG)(18) clusters indeed adopt the same
      structure as that of Au(25)(SCH(2)CH(2)Ph)(18). This conclusion is also valid for
      other types of thiolate-capped Au(25) clusters, including hexyl- and
      dodecylthiolates. Interestingly, the chiral optical responses (e.g., circular
      dichroism (CD) signals in the visible wavelength region) from the Au(25)(SG)(18)
      clusters seem to be imparted by the chiral glutathione ligands because no similar
      CD signals were observed in Au(25)(SCH(2)CH(2)Ph)(18).

PMID- 19379013
TI  - Solubilization of poly{1,4-phenylene-[9,9-bis(4-phenoxy-butylsulfonate)]fluorene
      2,7-diyl} in water by nonionic amphiphiles.
AB  - In the presence of the nonionic alkyloxyethylene surfactant n
      dodecylpentaoxyethylene glycol ether (C12E5), the anionic conjugated
      polyelectrolyte (CPE) poly{1,4-phenylene-[9,9-bis(4-phenoxy
      butylsulfonate)]fluorene-2,7-diyl} (PBS-PFP) dissolves in water, leading to a
      blue shift in fluorescence and dramatic increases in fluorescence quantum yields
      above the surfactant critical micelle concentration (cmc). No significant changes
      were seen with a poly(ethylene oxide) of similar size to the surfactant
      headgroup, confirming that specific surfactant-polyelectrolyte interactions are
      important. From UV-visible and fluorescence spectroscopy, dynamic light
      scattering (DLS), small-angle X-ray scattering (SAXS), cryogenic transmission
      electron microscopy (cryo-TEM), and electrical conductivity, together with our
      published NMR and small-angle neutron scattering (SANS) results, we provide a
      coherent model for this behavior in terms of breakup of PBS-PFP clusters through
      polymer-surfactant association leading to cylindrical aggregates containing
      isolated polymer chains. This is supported by molecular dynamics simulations,
      which indicate stable polymer-surfactant structures and also provide indications
      of the tendency of C12E5 to break up polymer clusters to form these mixed polymer
      surfactant aggregates. Radial electron density profiles of the cylindrical cross
      section obtained from SAXS results reveal the internal structure of such
      inhomogeneous species. DLS and cryo-TEM results show that at higher surfactant
      concentrations the micelles start to grow, possibly partially due to formation of
      long, threadlike species. Other alkyloxyethylene surfactants, together with
      poly(propylene glycol) and hydrophobically modified poly(ethylene glycol), also
      solubilize this polymer in water, and it is suggested that this results from a
      balance between electrostatic (or ion-dipole), hydrophilic, and hydrophobic
      interactions. There is a small, but significant, dependence of the emission
      maximum on the local environment.

PMID- 19379014
TI  - An innovative method to study target protein-drug interactions by mass
      spectrometry.
AB  - We report the combination of chemical cross-linking and high-resolution mass
      spectrometry for analyzing conformational changes in target proteins that are
      induced by drug binding. With this approach conformational changes in the
      peroxisome proliferator-activated receptor alpha (PPARalpha) upon binding of low
      molecular weight compounds were readily detected, proving that the strategy
      provides a basis to efficiently characterize target protein-drug interactions.

PMID- 19379016
TI  - Genetic erosion and population resilience in Daphnia longispina O.F. Muller under
      simulated predation and metal pressures.
AB  - This study investigated the effects of nonselective predation (culling) and metal
      toxicity on the genetic diversity of laboratory populations of the cladoceran
      Daphnia longispina. Populations, comprising five clones differing in their
      sensitivity to lethal concentrations of a metal-rich mine drainage effluent, were
      subjected to all possible combinations of three levels (absent, weak, and strong)
      of each stressor. Observed population densities were compared to those expected
      from a life history experiment, and clone frequencies were determined by allozyme
      profiling. Culling did not affect population density, although clonal diversity
      was higher than the control. Populations stressed by mine drainage recovered to
      their initial densities within 12 days, though the most sensitive genotypes
      disappeared under both weak and strong metal stress levels. Because the surviving
      resistant clones were shown to be the most sensitive ones to other chemicals (Cd
      and H+), it is suggested that successive inputs of partially lethal
      concentrations of different chemicals can lead to the disappearance of the
      population, even if the time between inputs is large enough to allow density
      recovery. These results suggest that changes in abundance are not enough to
      evaluate ecological effects of chemicals on the environment and information on co
      tolerance and multiple tolerance within populations is highly valuable to prevent
      their extinction. Moreover, populations exposed to low levels of both stressors
      showed clonal diversity levels identical to controls, highlighting the importance
      of low level effects of nonselective stressors in the maintenance of high clonal
      diversity levels in Daphnia populations, and thus further supporting the
      intermediate disturbance hypothesis.

PMID- 19379015
TI  - Conformationally constrained analogues of diacylglycerol (DAG). 31. Modulation of
      the biological properties of diacylgycerol lactones (DAG-lactones) containing
      rigid-rod acyl groups separated from the core lactone by spacer units of
      different lengths.
AB  - Diacylglycerol lactones built with a rigid 4-[(methylphenyl)ethynyl]phenyl rod
      that is separated from the exocyclic acylcarbonyl of the DAG-lactone core by a
      spacer unit of variable length were synthesized and studied. Binding affinities
      for a panel of classical and novel PKC isozymes in two different phospholipid
      environments, one corresponding to the plasma membrane of cells, were determined.
      The kinetics and site of translocation for the PKC isozymes alpha and delta upon
      treatment with the compounds were also studied as well as the early response of
      ERK phosphorylation and the late response of induction of apoptosis in the human
      prostatic carcinoma cell line LNCaP. Finally, the compounds were evaluated in
      terms of their interaction with biomimetic lipid/polydiacetylene membranes by the
      associated chromatic response. The different spatial disposition of the rigid
      structural motif on the DAG-lactones contributes to differential activity.

PMID- 19379017
TI  - Arsenate toxicity for wheat and lettuce in six Chinese soils with different
      properties.
AB  - To assess soil arsenic (As, in the form of arsenate) toxicity to plants, 6-d root
      elongation tests on wheat (Triticum aestivum L.) and lettuce (Lactuca sativa)
      were conducted in six Chinese soils freshly spiked with As. Plants were treated
      with 7 or 10 levels of As to establish concentration-effect curves. Median
      effective concentration and 10% effective concentration values were derived with
      regression analysis to measure As toxic potencies, and no-observed-effect
      concentration was determined by comparison with a control to elucidate thresholds
      of As to the two plant species. The median effective concentration values for As
      varied from 159 to 683 mg/kg for wheat and 59 to 426 mg/kg for lettuce, and the
      10% effective concentration values varied from 79 to 270 mg/kg for wheat and 20
      to 156 mg/kg for lettuce. The result suggests that lettuce is a more sensitive
      species for monitoring soil As contamination. With the same level of As spiked,
      soil toxicity for a plant showed a tendency of fluvoaquic soil toward red soil or
      black soil toward paddy soil. The phytotoxicity of As was negatively correlated
      with soil amorphous iron content extracted with ammonium oxalate. The overall
      results from the present work illustrate the necessity of considering soil
      properties in assessing soil As contamination.

PMID- 19379018
TI  - Implicit measures: A normative analysis and review.
AB  - Implicit measures can be defined as outcomes of measurement procedures that are
      caused in an automatic manner by psychological attributes. To establish that a
      measurement outcome is an implicit measure, one should examine (a) whether the
      outcome is causally produced by the psychological attribute it was designed to
      measure, (b) the nature of the processes by which the attribute causes the
      outcome, and (c) whether these processes operate automatically. This normative
      analysis provides a heuristic framework for organizing past and future research
      on implicit measures. The authors illustrate the heuristic function of their
      framework by using it to review past research on the 2 implicit measures that are
      currently most popular: effects in implicit association tests and affective
      priming tasks. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 19379019
TI  - Methodological issues in the validation of implicit measures: comment on De
      Houwer, Teige-Mocigemba, Spruyt, and Moors (2009).
AB  - J. De Houwer, S. Teige-Mocigemba, A. Spruyt, and A. Moors's normative analysis of
      implicit measures provides an excellent clarification of several conceptual
      ambiguities surrounding the validation and use of implicit measures. The current
      comment discusses an important, yet unacknowledged, implication of J. De Houwer
      et al.'s analysis, namely, that investigations addressing the proposed
      implicitness criterion (i.e., does the relevant psychological attribute influence
      measurement outcomes in an automatic fashion?) will be susceptible to fundamental
      misinterpretations if they are conducted independently of the proposed what
      criterion (i.e., is the measurement outcome causally produced by the
      psychological attribute the measurement procedure was designed to assess?). As a
      solution, it is proposed that experimental validation studies should be combined
      with a correlational approach in order to determine whether a given manipulation
      influenced measurement scores via variations in the relevant psychological
      attribute or via secondary sources of systematic variance. (PsycINFO Database
      Record (c) 2009 APA, all rights reserved).

PMID- 19379020
TI  - (Part of) the case for a pragmatic approach to validity: comment on De Houwer,
      Teige-Mocigemba, Spruyt, and Moors (2009).
AB  - In their review of validity of the Implicit Association Test and affective
      priming, J. De Houwer, S. Teige-Mocigemba, A. Spruyt, and A. Moors identified
      validity with establishment of "basic theoretical understanding" of the measures.
      It is agreed that theoretical understanding has an important role in making
      measures more valid and useful. Nevertheless, the authors conclude that
      scientific advancement will more often be well served by prioritizing pragmatic
      goals of establishing the predictive validity of the measures and their adequate
      sensitivity to individual differences. (PsycINFO Database Record (c) 2009 APA,
      all rights reserved).

PMID- 19379021
TI  - Theoretical claims necessitate basic research: reply to Gawronski, Lebel, Peters,
      and Banse (2009) and Nosek and Greenwald (2009).
AB  - The authors of this reply article note that B. Gawronski, E. P. LeBel, K. R.
      Peters, and R. Banse (a) expressed agreement in their comment with the analysis
      put forward in the target article (J. De Houwer, S. Teige-Mocigemba, A. Spruyt, &
      A. Moors) and (b) pointed to a further implication for the way in which the
      implicitness of a measure should be examined. The current authors note that B. A.
      Nosek and A. G. Greenwald, on the other hand, raised questions in their comment
      about the definition of the concept "implicit" in the target article, arguing for
      a fundamentally different approach to measurement that emphasizes not theoretical
      understanding but usefulness for predicting behavior. In this reply, the current
      authors respond to these comments and argue that when theoretical claims are made
      about measures, these claims should be backed up with appropriate evidence. In
      the absence of basic research, measures and their relation to behavior can only
      be described. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 19379022
TI  - The cognitive and neural correlates of tactile memory.
AB  - Tactile memory systems are involved in the storage and retrieval of information
      about stimuli that impinge on the body surface and objects that people explore
      haptically. Here, the authors review the behavioral, neuropsychological,
      neurophysiological, and neuroimaging research on tactile memory. This body of
      research reveals that tactile memory can be subdivided into a number of
      functionally distinct neurocognitive subsystems, just as is the case with
      auditory and visual memory. Some of these subsystems are peripheral and short
      lasting and others are more central and long lasting. The authors highlight
      evidence showing that the representation of tactile information interacts with
      information about other sensory attributes (e.g., visual, auditory, and
      kinaesthetic) of objects/events that people perceive. This fact suggests that at
      least part of the neural network involved in the memory for touch might be shared
      among different sensory modalities. In particular, multisensory/amodal
      information-processing networks seem to play a leading role in the storage of
      tactile information in the brain. (PsycINFO Database Record (c) 2009 APA, all
      rights reserved).

PMID- 19379024
TI  - Internal and external moderators of the effect of variety on food intake.
AB  - Many factors contribute to how much we eat. One such factor is the variety of
      different foods available. The current article reviews the variety literature
      with a specific focus on the factors that moderate the effects of variety on food
      intake and that moderate the processes that may underlie the variety effect
      (i.e., sensory-specific satiety and monotony). The moderators have been
      categorized as being of either an internal nature or an external nature. The
      literature suggests that internal moderators, including characteristics such as
      gender, weight, and dietary restraint, do not act as moderators of the variety
      effect. One possible exception to the absence of internal moderators is old age.
      Alternatively, external moderators, such as particular properties of food and the
      eater's perception of the situation, appear to affect the strength of the variety
      effect on intake to some degree. An evolutionary hypothesis may account for the
      distinct roles that internal and external variables play in moderating the
      variety effect. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 19379025
TI  - Mechanisms of masked priming: a meta-analysis.
AB  - The extent to which unconscious information can influence behavior has been a
      topic of considerable debate throughout the history of psychology. A frequently
      used method for studying subliminal processing is the masked priming paradigm.
      The authors focused on studies in which this paradigm was used. Their aim was
      twofold: first, to assess the magnitude of subliminal priming across the
      literature and to determine whether subliminal primes are processed semantically,
      and second, to examine potential moderators of priming effects. The authors found
      significant priming in their analyses, indicating that unconsciously presented
      information can influence behavior. Furthermore, priming was observed under
      circumstances in which a nonsemantic interpretation could not fully explain the
      effects, suggesting that subliminally presented information can be processed
      semantically. Nonetheless, the nonsemantic processing of primes is enhanced and
      priming effects are boosted when the experimental context allows the formation of
      automatic stimulus-response mappings. This quantitative review also revealed
      several moderators that influence the strength of priming. (PsycINFO Database
      Record (c) 2009 APA, all rights reserved).

PMID- 19379026
TI  - Moral agency and the sexual transmission of HIV.
AB  - Sexual transmission of HIV occurs because an infected person has unprotected sex
      with a previously uninfected person. The majority of HIV infections are
      transmitted by individuals who are unaware of their infection, and most persons
      who are diagnosed with HIV significantly reduce or eliminate risk behaviors once
      they learn they have HIV. However, a minority of known-infected individuals
      engage in transmission risk behavior, sometimes without disclosure to their
      partners. Such behavior may involve a breakdown or temporary suspension of moral
      mechanisms, such as personal responsibility beliefs and anticipatory self
      evaluative reactions to one's behavior. The present article reviews the
      literature on sexual transmission risk behavior within A. Bandura's (1999)
      theoretical framework of moral agency. The article first reviews evidence for the
      operation of moral agency in transmission risk behavior and HIV status
      disclosure. Next, suggestive evidence is presented for the operation of
      mechanisms of moral disengagement described by Bandura. Finally, the article
      reviews a small number of interventions that have been shown to be effective in
      reducing transmission risk behavior, through the lens of moral agency, and make
      recommendations for future intervention research. (PsycINFO Database Record (c)
      2009 APA, all rights reserved).

PMID- 19379023
TI  - The relationship between eating disorder not otherwise specified (EDNOS) and
      officially recognized eating disorders: meta-analysis and implications for DSM.
AB  - Eating disorder not otherwise specified (EDNOS) is the most prevalent eating
      disorder (ED) diagnosis. In this meta-analysis, the authors aimed to inform
      Diagnostic and Statistical Manual of Mental Disorders revisions by comparing the
      psychopathology of EDNOS with that of the officially recognized EDs: anorexia
      nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). A
      comprehensive literature search identified 125 eligible studies (published and
      unpublished) appearing in the literature from 1987 to 2007. Random effects
      analyses indicated that whereas EDNOS did not differ significantly from AN and
      BED on eating pathology or general psychopathology, BN exhibited greater eating
      and general psychopathology than EDNOS. Moderator analyses indicated that EDNOS
      groups who met all diagnostic criteria for AN except for amenorrhea did not
      differ significantly from full syndrome cases. Similarly, EDNOS groups who met
      all criteria for BN or BED except for binge frequency did not differ
      significantly from full syndrome cases. Results suggest that EDNOS represents a
      set of disorders associated with substantial psychological and physiological
      morbidity. Although certain EDNOS subtypes could be incorporated into existing
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American
      Psychiatric Association, 1994) categories, others-such as purging disorder and
      non-fat-phobic AN-may be best conceptualized as distinct syndromes. (PsycINFO
      Database Record (c) 2009 APA, all rights reserved).

PMID- 19379028
TI  - Implicit misattribution as a mechanism underlying evaluative conditioning.
AB  - Evaluative conditioning (EC) refers to the formation or change of an attitude
      toward an object, following that object's pairing with positively or negatively
      valenced stimuli. The authors provide evidence that EC can occur through an
      implicit misattribution mechanism in which an evaluative response evoked by a
      valenced stimulus is incorrectly and implicitly attributed to another stimulus,
      forming or changing an attitude toward this other stimulus. In 5 studies, the
      authors measured or manipulated variables related to the potential for the
      misattribution of an evaluation, or source confusability. Greater EC was observed
      when participants' eye gaze shifted frequently between a valenced and a neutral
      stimulus (Studies 1 & 2), when the 2 stimuli appeared in close spatial proximity
      (Study 3), and when the neutral stimulus was made more perceptually salient than
      was the valenced stimulus, due to the larger size of the neutral stimulus (Study
      4). In other words, conditions conducive to source confusability increased EC.
      Study 5 provided evidence for multiple mechanisms of EC by comparing the effects
      of mildly evocative valenced stimuli (those evoking responses that might more
      easily be misattributed to another object) with more strongly evocative stimuli.

PMID- 19379029
TI  - Multiple social identities and stereotype threat: imbalance, accessibility, and
      working memory.
AB  - In 4 experiments, the authors showed that concurrently making positive and
      negative self-relevant stereotypes available about performance in the same
      ability domain can eliminate stereotype threat effects. Replicating past work,
      the authors demonstrated that introducing negative stereotypes about women's math
      performance activated participants' female social identity and hurt their math
      performance (i.e., stereotype threat) by reducing working memory. Moving beyond
      past work, it was also demonstrated that concomitantly presenting a positive self
      relevant stereotype (e.g., college students are good at math) increased the
      relative accessibility of females' college student identity and inhibited their
      gender identity, eliminating attendant working memory deficits and contingent
      math performance decrements. Furthermore, subtle manipulations in questions
      presented in the demographic section of a math test eliminated stereotype threat
      effects that result from women reporting their gender before completing the test.
      This work identifies the motivated processes through which people's social
      identities became active in situations in which self-relevant stereotypes about a
      stigmatized group membership and a nonstigmatized group membership were
      available. In addition, it demonstrates the downstream consequences of this
      pattern of activation on working memory and performance.

PMID- 19379030
TI  - Priming and authorship ascription: when nonconscious goals turn into conscious
      experiences of self-agency.
AB  - The conscious experience of self-agency (i.e., the feeling that one causes one's
      own actions and their outcomes) is fundamental to human self-perception. Four
      experiments explored how experienced self-agency arises from a match between
      nonconsciously activated outcome representations and the subsequent production of
      the outcome and explored specifically how implicit motivation to produce the
      outcome may impinge on this process. Participants stopped a rapidly presented
      sequence of colors on a computer screen. Subsequently, they were presented with
      what could be the color on which they had stopped the sequence or a color that
      was randomly chosen by the computer. Agency ratings after each trial revealed
      that priming outcomes (a specific color) just before the outcome was produced
      enhanced experienced self-agency. Importantly, priming outcomes relatively far in
      advance also augmented self-agency, but only if the outcome was attached to
      positive affect and thus operating as a nonconscious goal maintaining the outcome
      representation active over time. As such, these studies show how the mechanisms
      underlying nonconscious goal pursuit promote experiences of self-agency, thus
      integrating 2 lines of research that so far have led separate lives.

PMID- 19379027
TI  - A biosocial developmental model of borderline personality: Elaborating and
      extending Linehan's theory.
AB  - Over the past several decades, research has focused increasingly on developmental
      precursors to psychological disorders that were previously assumed to emerge only
      in adulthood. This change in focus follows from the recognition that complex
      transactions between biological vulnerabilities and psychosocial risk factors
      shape emotional and behavioral development beginning at conception. To date,
      however, empirical research on the development of borderline personality is
      extremely limited. Indeed, in the decade since M. M. Linehan initially proposed a
      biosocial model of the development of borderline personality disorder, there have
      been few attempts to test the model among at-risk youth. In this review, diverse
      literatures are reviewed that can inform understanding of the ontogenesis of
      borderline pathology, and testable hypotheses are proposed to guide future
      research with at-risk children and adolescents. One probable pathway is
      identified that leads to borderline personality disorder; it begins with early
      vulnerability, expressed initially as impulsivity and followed by heightened
      emotional sensitivity. These vulnerabilities are potentiated across development
      by environmental risk factors that give rise to more extreme emotional,
      behavioral, and cognitive dysregulation. (PsycINFO Database Record (c) 2009 APA,
      all rights reserved).

PMID- 19379031
TI  - Aggress to impress: hostility as an evolved context-dependent strategy.
AB  - Given the high costs of aggression, why have people evolved to act aggressively?
      Comparative biologists have frequently observed links between aggression, status,
      and mating in nonhuman animals. In this series of experiments, the authors
      examined the effects of status, competition, and mating motives on men's and
      women's aggression. For men, status motives increased direct aggression (face-to
      face confrontation). Men's aggression was also boosted by mating motives, but
      only when observers were other men. For women, both status and mating motives
      increased indirect aggression (e.g., socially excluding the perpetrator).
      Although neither status nor mating motives increased women's direct aggression,
      women did become more directly aggressive when motivated to compete for scarce
      resources. These context- and sex-specific effects on human aggression contribute
      to a broader understanding of the functional nature of aggressive behavior.

PMID- 19379032
TI  - Identity fusion: the interplay of personal and social identities in extreme group
      behavior.
AB  - The authors propose that when people become fused with a group, their personal
      and social identities become functionally equivalent. Two hypotheses follow from
      this proposition. First, activating either personal or social identities of fused
      persons should increase their willingness to endorse extreme behaviors on behalf
      of the group. Second, because personal as well as social identities support group
      related behaviors of fused persons, the 2 forms of identity may combine
      synergistically, fostering exceptionally high levels of extreme behavior. Support
      for these hypotheses came from 5 preliminary studies and 3 experiments. In
      particular, fused persons were more willing to fight or die for the group than
      nonfused persons, especially when their personal or social identities had been
      activated. The authors conclude that among fused persons, both the personal and
      social self may energize and direct group-related behavior. Implications for
      related theoretical approaches and for conceptualizing the relationship between
      personal identities, social identities, and group processes are discussed.

PMID- 19379033
TI  - Evidence that a simpatico self-schema accounts for differences in the self
      concepts and social behavior of Latinos versus Whites (and Blacks).
AB  - On the basis of the assumption that Latino Americans use a simpatico self-schema
      more than White Americans do, the authors predicted that the effects of this
      difference would be evident in the participants' self-concepts and social
      behavior. As predicted, Studies 1 and 2 revealed that Latino participants
      reported significantly more simpatico-related terms in their spontaneous self
      concepts than did White participants. Complementing these findings, Study 3a
      revealed that the level of interactional involvement and the perceived quality of
      initial same-sex interactions was significantly enhanced by the presence of
      Latino dyad members. Study 3b tested the prediction that the content of the dyad
      members' thoughts and feelings would reveal a greater use of the simpatico self
      schema by the Latino participants. This prediction was confirmed, and follow-up
      analyses indicated that a simpatico self-schema plays an important mediating role
      in the subjective experience and social behavior of Latino individuals.

PMID- 19379034
TI  - Liberals and conservatives rely on different sets of moral foundations.
AB  - How and why do moral judgments vary across the political spectrum? To test moral
      foundations theory (J. Haidt & J. Graham, 2007; J. Haidt & C. Joseph, 2004), the
      authors developed several ways to measure people's use of 5 sets of moral
      intuitions: Harm/care, Fairness/reciprocity, Ingroup/loyalty, Authority/respect,
      and Purity/sanctity. Across 4 studies using multiple methods, liberals
      consistently showed greater endorsement and use of the Harm/care and
      Fairness/reciprocity foundations compared to the other 3 foundations, whereas
      conservatives endorsed and used the 5 foundations more equally. This difference
      was observed in abstract assessments of the moral relevance of foundation-related
      concerns such as violence or loyalty (Study 1), moral judgments of statements and
      scenarios (Study 2), "sacredness" reactions to taboo trade-offs (Study 3), and
      use of foundation-related words in the moral texts of religious sermons (Study
      4). These findings help to illuminate the nature and intractability of moral
      disagreements in the American "culture war."

PMID- 19379035
TI  - Cultural borders and mental barriers: the relationship between living abroad and
      creativity.
AB  - Despite abundant anecdotal evidence that creativity is associated with living in
      foreign countries, there is currently little empirical evidence for this
      relationship. Five studies employing a multimethod approach systematically
      explored the link between living abroad and creativity. Using both individual and
      dyadic creativity tasks, Studies 1 and 2 provided initial demonstrations that
      time spent living abroad (but not time spent traveling abroad) showed a positive
      relationship with creativity. Study 3 demonstrated that priming foreign living
      experiences temporarily enhanced creative tendencies for participants who had
      previously lived abroad. In Study 4, the degree to which individuals had adapted
      to different cultures while living abroad mediated the link between foreign
      living experience and creativity. Study 5 found that priming the experience of
      adapting to a foreign culture temporarily enhanced creativity for participants
      who had previously lived abroad. The relationship between living abroad and
      creativity was consistent across a number of creativity measures (including those
      measuring insight, association, and generation), as well as with masters of
      business administration and undergraduate samples, both in the United States and
      Europe, demonstrating the robustness of this phenomenon.

PMID- 19379036
TI  - Need for cognition, task difficulty, and the formation of performance
      expectancies.
AB  - In the present article, the authors analyze how performance expectancies are
      generated and how they affect actual performance. The authors predicted that task
      difficulty would affect performance expectancies only when cognitive motivation
      (i.e., need for cognition [NFC]) and cognitive capacity are high. This should be
      the case because analyzing task difficulty is a process requiring cognitive
      capacity as well as cognitive motivation. The findings supported the expected NFC
      x Difficulty interaction for the formation of performance expectancies (Study 1,
      Study 2), but only when cognitive capacity was high (Study 2). The authors also
      predicted that expectancies would affect actual performance only if the task is
      difficult and if task difficulty is taken into account when the expectancy is
      generated. This hypothesis was supported: Significant relations between
      performance expectancies and actual performance were found only for difficult
      tasks and for participants higher in NFC. Studies 5 and 6 showed clear evidence
      that the NFC x Difficulty interaction could not be explained by differences in
      the use of task-specific self-concepts. The findings were robust across academic,
      social, and physical tasks.

PMID- 19379037
TI  - Terror management theory and self-esteem revisited: the roles of implicit and
      explicit self-esteem in mortality salience effects.
AB  - Three studies tested the roles of implicit and/or explicit self-esteem in
      reactions to mortality salience. In Study 1, writing about death versus a control
      topic increased worldview defense among participants low in implicit self-esteem
      but not among those high in implicit self-esteem. In Study 2, a manipulation to
      boost implicit self-esteem reduced the effect of mortality salience on worldview
      defense. In Study 3, mortality salience increased the endorsement of positive
      personality descriptions but only among participants with the combination of low
      implicit and high explicit self-esteem. These findings indicate that high
      implicit self-esteem confers resilience against the psychological threat of
      death, and therefore the findings provide direct support for a fundamental tenet
      of terror management theory regarding the anxiety-buffering role of self-esteem.

PMID- 19379038
TI  - Recognition ROCs are curvilinear-or are they? On premature arguments against the
      two-high-threshold model of recognition.
AB  - Recent reviews of recognition receiver operating characteristics (ROCs) claim
      that their curvilinear shape rules out threshold models of recognition. However,
      the shape of ROCs based on confidence ratings is not diagnostic to refute
      threshold models, whereas ROCs based on experimental bias manipulations are.
      Also, fitting predicted frequencies to actual data is a more sensitive method for
      model comparisons than ROC regressions. In a reanalysis of 59 published data
      sets, the 2-high-threshold model (2HTM) fit the data better than an unequal
      variance signal detection model in about half of the cases. Three recognition
      experiments with experimental bias manipulation were conducted that yielded
      linear ROCs and a better fit of the 2HTM in all cases. On the basis of actual
      data and a simulation, the authors argue that both models are at least equally
      valid as measurement tools and can perhaps be integrated theoretically.

PMID- 19379039
TI  - The role of item strength in retrieval-induced forgetting.
AB  - In 3 experiments, the role of item strength in the retrieval-induced forgetting
      paradigm was tested. According to the inhibition theory of forgetting proposed by
      M. C. Anderson, R. A. Bjork, and E. L. Bjork (1994), retrieval-induced forgetting
      should be larger for items that are more strongly associated with the category
      cue. In the present experiments, the authors varied item strength on the study
      list by manipulating the position of an item within its category (Experiments 1
      and 2) and by the number of presentations in the study phase (Experiment 3).
      Contrary to the predictions from inhibition theory, in all 3 experiments,
      stronger items did not show more retrieval-induced forgetting than weaker items.

PMID- 19379040
TI  - Sandwich priming: a method for overcoming the limitations of masked priming by
      reducing lexical competitor effects.
AB  - An orthographically similar masked nonword prime facilitates responding in a
      lexical decision task (Forster & Davis, 1984). Recently, this masked priming
      paradigm has been used to evaluate models of orthographic coding--odels that
      attempt to quantify prime-target similarity. One general finding is that priming
      effects often do not occur when prime-target similarity is moderate, a result
      that the authors interpret as being due to uncontrolled effects of lexical
      inhibition. In the present research, a new version of the masked priming
      paradigm, sandwich priming, was introduced in an effort to minimize the impact of
      lexical inhibition. Masked sandwich priming involves briefly presenting the
      target itself prior to the presentation of each prime. Results indicate that the
      new paradigm was successful. The predicted priming effects were observed for
      Guerrera and Forster's (2008) T-All primes (e.g., avacitno-VACATION) and for
      primes differing from their targets at 3 letter positions (e.g., coshure-CAPTURE)
      effects that are not found with the conventional masked priming paradigm. In
      addition to demonstrating the usefulness of the sandwich priming technique, these
      results also support the assumption that inhibitory processes play an important
      role in lexical processing.

PMID- 19379042
TI  - Effects of spatial cueing on representational momentum.
AB  - Effects of a spatial cue on representational momentum were examined. If a cue was
      present during or after target motion and indicated the location at which the
      target would vanish or had vanished, forward displacement of that target
      decreased. The decrease in forward displacement was larger when cues were present
      after target motion than when cues were present during target motion. If a cue
      was present during target motion, high-relevant cues (that indicated the final
      location of the target) led to larger decreases in forward displacement than did
      low-relevant cues (that indicated only the horizontal coordinate of the final
      location of the target). If a cue was present after target motion, there was a
      trend for low-relevant cues to lead to larger decreases in forward displacement
      than did high-relevant cues. Possible explanations involving displacement of the
      cue or landmark attraction are considered. Implications for the relationship of
      attention and representational momentum, and for whether representational
      momentum reflects an automatic process, are discussed.

PMID- 19379043
TI  - Causal learning with local computations.
AB  - The authors proposed and tested a psychological theory of causal structure
      learning based on local computations. Local computations simplify complex
      learning problems via cues available on individual trials to update a single
      causal structure hypothesis. Structural inferences from local computations make
      minimal demands on memory, require relatively small amounts of data, and need not
      respect normative prescriptions as inferences that are principled locally may
      violate those principles when combined. Over a series of 3 experiments, the
      authors found (a) systematic inferences from small amounts of data; (b)
      systematic inference of extraneous causal links; (c) influence of data
      presentation order on inferences; and (d) error reduction through pretraining.
      Without pretraining, a model based on local computations fitted data better than
      a Bayesian structural inference model. The data suggest that local computations
      serve as a heuristic for learning causal structure.

PMID- 19379041
TI  - Should I stay or should I switch? A cost-benefit analysis of voluntary language
      switching in young and aging bilinguals.
AB  - Bilinguals spontaneously switch languages in conversation even though laboratory
      studies reveal robust cued language switching costs. The authors investigated how
      voluntary-switching costs might differ when switches are voluntary. Younger
      (Experiments 1-2) and older (Experiment 3) Spanish-English bilinguals named
      pictures in 3 conditions: (a) dominant-language only, (b) nondominant-language
      only, and (c) using "whatever language comes to mind" (in Experiment 2, "using
      each language about half the time"). Most bilinguals, particularly balanced
      bilinguals, voluntarily mixed languages even though switching was costly. Unlike
      with cued switching, voluntary switching sometimes facilitated responses, switch
      costs were not greater for the dominant language, and age effects on language
      mixing and switching were limited. This suggests that the freedom to mix
      languages voluntarily allows unbalanced and older bilinguals to function more
      like balanced and younger bilinguals. Voluntary switch costs reveal an expanded
      role for inhibitory control in bilingual language production and imply a
      mandatory separation by language in bilingual lexical selection.

PMID- 19379044
TI  - Blocking of goal-location learning based on shape.
AB  - Using desktop, computer-simulated virtual environments (VEs), the authors
      conducted 5 experiments to investigate blocking of learning about a goal location
      based on Shape B as a consequence of preliminary training to locate that goal
      using Shape A. The shapes were large 2-dimensional horizontal figures on the
      ground. Blocking of spatial learning was found when the initially trained Shape A
      was presented in the context of auxiliary shapes that were anticipated to be
      irrelevant to goal localization. When Shape A was initially presented in the
      absence of these auxiliary shapes, no evidence of blocking between shapes was
      apparent. The results are discussed in terms of the similarity between spatial
      and other forms of contingency learning, the operation of a specialized geometric
      module, and changes in attention as a consequence of discrimination learning.

PMID- 19379045
TI  - Affective and deliberative processes in risky choice: age differences in risk
      taking in the Columbia Card Task.
AB  - The authors investigated risk taking and underlying information use in 13- to 16-
      and 17- to 19-year-old adolescents and in adults in 4 experiments, using a novel
      dynamic risk-taking task, the Columbia Card Task (CCT). The authors investigated
      risk taking under differential involvement of affective versus deliberative
      processes with 2 versions of the CCT, constituting the most direct test of a dual
      system explanation of adolescent risk taking in the literature so far. The "hot"
      CCT was designed to trigger more affective decision making, whereas the "cold"
      CCT was designed to trigger more deliberative decision making. Differential
      involvement of affective versus deliberative processes in the 2 CCT versions was
      established by self-reports and assessment of electrodermal activity. Increased
      adolescent risk taking, coupled with simplified information use, was found in the
      hot but not the cold condition. Need-for-arousal predicted risk taking only in
      the hot condition, whereas executive functions predicted information use in the
      cold condition. Results are consistent with recent dual-system explanations of
      risk taking as the result of competition between affective processes and
      deliberative cognitive-control processes, with adolescents' affective system
      tending to override the deliberative system in states of heightened emotional
      arousal.

PMID- 19379046
TI  - Learning mode and exemplar sequencing in unsupervised category learning.
AB  - Exemplar sequencing effects in incidental and intentional unsupervised category
      learning were investigated to illuminate how people form categories without an
      external teacher. Stimuli were perfectly separable into 2 categories based on 1
      of 2 dimensions of variation. Sequencing of the first 20 training stimuli was
      manipulated. In the blocked condition, 10 Category A stimuli were followed by 10
      Category B stimuli. In the intermixed condition, these 20 stimuli were ordered
      randomly. Experiment 1 revealed an interaction between learning mode and
      sequence, with better intentional learning for intermixed sequences but better
      incidental learning for blocked sequences. Experiment 2 showed that manipulating
      trial-to-trial variability along each dimension can impact intentional learning.
      Training sequences that emphasized variation along the category-relevant
      dimension resulted in better performance than sequences that emphasized variation
      along the category-irrelevant dimension. The results suggest that unsupervised
      category learning is influenced by the mode of learning and the order and nature
      of encountered exemplars.

PMID- 19379047
TI  - Perceive-decide-act, perceive-decide-act: how abstract is repetition-related
      decision learning?
AB  - Recent encounters with a stimulus often facilitate or "prime" future responses to
      the same or similar stimuli. However, studies are inconclusive as to whether
      changing the response that is required attenuates priming only for identical
      stimuli, or also for categorically related items. In 2 object priming
      experiments, the authors show that priming was eliminated if the initial decision
      associated with a stimulus changed on a later trial. This disruption of priming
      extended to perceptually and conceptually similar object exemplars and was found
      even when the classification tasks were uncorrelated with one another, many other
      items had intervened, and after only 1 prior encounter with a given stimulus.
      These outcomes are consistent with the rapid and automatic binding of a stimulus
      with a response into an episodic "instance" or "event file" and demonstrate that
      repetition-related decision learning is not hyperspecific but generalizes to new
      stimuli.

PMID- 19379048
TI  - Bindings between stimuli and multiple response codes dominate long-lag repetition
      priming in speeded classification tasks.
AB  - Repetition priming is often thought to reflect the facilitation of 1 or more
      processes engaged during initial and subsequent presentations of a stimulus.
      Priming can also reflect the formation of direct, stimulus-response (S-R)
      bindings, retrieval of which bypasses many of the processes engaged during the
      initial presentation. Using long-lag repetition priming of semantic
      classification of visual stimuli, the authors used task switches between study
      and test phases to reveal several signatures of S-R learning in Experiments 1
      through 5. Indeed, the authors found surprisingly little, if any, evidence of
      priming that could not be attributed to S-R learning, once they considered the
      possibility that stimuli are simultaneously bound to multiple, different response
      codes. Experiments 6 and 7 provided more direct evidence for independent
      contributions from at least 3 levels of response representation: the action
      (e.g., specific finger used), the decision (e.g., yes-no), and the task-specific
      classification (e.g., bigger-smaller). Although S-R learning has been discussed
      previously in many contexts, the present results go beyond existing theories of S
      R learning. Moreover, its dominant role brings into question many interpretations
      of priming during speeded classification tasks in terms of perceptual-conceptual
      processing.

PMID- 19379049
TI  - Strategies for revising judgment: how (and how well) people use others' opinions.
AB  - A basic issue in social influence is how best to change one's judgment in
      response to learning the opinions of others. This article examines the strategies
      that people use to revise their quantitative estimates on the basis of the
      estimates of another person. The authors note that people tend to use 2 basic
      strategies when revising estimates: choosing between the 2 estimates and
      averaging them. The authors developed the probability, accuracy, redundancy (PAR)
      model to examine the relative effectiveness of these two strategies across
      judgment environments. A surprising result was that averaging was the more
      effective strategy across a wide range of commonly encountered environments. The
      authors observed that despite this finding, people tend to favor the choosing
      strategy. Most participants in these studies would have achieved greater accuracy
      had they always averaged. The identification of intuitive strategies, along with
      a formal analysis of when they are accurate, provides a basis for examining how
      effectively people use the judgments of others. Although a portfolio of
      strategies that includes averaging and choosing can be highly effective, the
      authors argue that people are not generally well adapted to the environment in
      terms of strategy selection.

PMID- 19379050
TI  - Phonological typicality does not influence fixation durations in normal reading.
AB  - Using a word-by-word self-paced reading paradigm, T. A. Farmer, M. H.
      Christiansen, and P. Monaghan (2006) reported faster reading times for words that
      are phonologically typical for their syntactic category (i.e., noun or verb) than
      for words that are phonologically atypical. This result has been taken to suggest
      that language users are sensitive to subtle relationships between sound and
      syntactic function and that they make rapid use of this information in
      comprehension. The present article reports attempts to replicate this result
      using both eyetracking during normal reading (Experiment 1) and word-by-word self
      paced reading (Experiment 2). No hint of a phonological typicality effect emerged
      on any reading-time measure in Experiment 1, nor did Experiment 2 replicate
      Farmer et al.'s finding from self-paced reading. Indeed, the differences between
      condition means were not consistently in the predicted direction, as
      phonologically atypical verbs were read more quickly than phonologically typical
      verbs, on most measures. Implications for research on visual word recognition are
      discussed.

PMID- 19379051
TI  - Investigating the cause of language regularization in adults: memory constraints
      or learning effects?
AB  - When language learners are exposed to inconsistent probabilistic grammatical
      patterns, they sometimes impose consistency on the language instead of learning
      the variation veridically. The authors hypothesized that this regularization
      results from problems with word retrieval rather than from learning per se. One
      prediction of this, that easing the demands of lexical retrieval leads to less
      regularization, was tested. Adult learners were exposed to a language containing
      inconsistent probabilistic patterns and were tested with either a standard
      production task or one of two tasks that reduced the demands of lexical
      retrieval. As predicted, participants tested with the modified tasks more closely
      matched the probability of the inconsistent items than did those tested with the
      standard task.

PMID- 19379052
TI  - Metamemory judgments and the benefits of repeated study: improving recall
      predictions through the activation of appropriate knowledge.
AB  - Correspondence between judgments of learning (JOLs) and actual recall tends to be
      poor when the same items are studied and recalled multiple times (e.g., A.
      Koriat, L. Sheffer, & H. Ma'ayan, 2002). The authors investigated whether making
      relevant metamemory knowledge more salient would improve the association between
      actual and predicted recall as a function of repeated exposure to the same study
      list. In 2 experiments, participants completed 4 study-recall phases involving
      the same list of items. In addition to having participants make item-by-item JOLs
      during each study phase, after the 1st study-recall phase participants also
      generated change-in-recall estimates as to how many more or fewer words they
      would recall given another exposure to the same study list. This estimation
      procedure was designed to highlight repeated study as a factor that can
      contribute to recall performance. Activating metamemory knowledge about the
      benefits of repeated study for recall in this way allowed participants to
      accurately express this knowledge in a free-recall context (Experiment 2), but
      less so when the memory test was cued recall (Experiment 1).

PMID- 19379054
TI  - Bilingualism reduces native-language interference during novel-word learning.
AB  - The goal of the present work was to examine the effects of bilingualism on
      adults' ability to resolve cross-linguistic inconsistencies in orthography-to
      phonology mappings during novel-word learning. English monolinguals and English
      Spanish bilinguals learned artificially constructed novel words that overlapped
      with English orthographically but diverged from English phonologically. Native
      language orthographic information presented during learning interfered with
      encoding of novel words in monolinguals but not in bilinguals. In general,
      bilinguals outperformed monolinguals on the word-learning task. These findings
      indicate that knowledge of 2 languages facilitates word learning and shields
      English-Spanish bilinguals from interference associated with cross-linguistic
      inconsistencies in letter-to-phoneme mappings.

PMID- 19379055
TI  - Treatment of acute ischemic stroke: role of ischemic tolerance in intravenous and
      endovascular therapies.

PMID- 19379056
TI  - Challenges in the diagnosis and management of transient ischemic attack.

PMID- 19379057
TI  - Unraveling the paradoxical link between obesity and heart failure: the role of
      adipocytokines.

PMID- 19379059
TI  - Angiotensin-converting enzyme inhibition by perindopril in the treatment of
      cardiovascular disease.
AB  - The angiotensin-converting enzyme (ACE) inhibitor perindopril (Coversyl) is a
      long-acting lipophilic drug with a high-tissue affinity for the ACE. ACE
      inhibition by perindopril has two main effects: it inhibits the angiotensin II
      formation and potentiates bradykinin. Perindopril is one of the ACE inhibitors
      that has been extensively studied in randomized clinical trials within various
      patient populations. The clinical efficacy has been demonstrated in patients with
      hypertension, diabetes mellitus, cerebrovascular disease, stable coronary artery
      disease (CAD) and heart failure. Perindopril has a positive safety and
      tolerability profile. Therefore, perindopril, as an ACE inhibitor, has an
      established place in the major clinical treatment guidelines. This article
      discusses several studies that have shown that an antihypertensive treatment with
      perindopril reduces and prevents cardiovascular events in a large range of
      patients with established vascular disease. The observed cardioprotective
      benefits of perindopril were independent of blood pressure. The outcome of these
      and other trials support the concept of specific cardioprotective properties of
      ACE inhibition by perindopril in addition to the blood pressure-lowering effects,
      such as anti-atherosclerotic, anti-inflammatory and antithrombotic properties. In
      addition, the observed consistency of the treatment benefit across subgroups
      indicates that the absolute benefits conferred by treatment are mainly
      established by each patient's future risk of vascular complications, rather than
      their initial blood pressure level or other risk factors. This article describes
      these issues according to the main studies with perindopril or perindopril-based
      regimens, concluding that the blood pressure-dependent and -independent
      cardioprotective effects extend to all patients with vascular disease. This
      concept supports the provision of ACE inhibitor-based treatment, not on the basis
      of arbitrary cut-off points for blood pressure but rather on assessment of
      vascular risk, which is raised in patients with stable CAD, diabetes and stroke.

PMID- 19379061
TI  - Clinical outcomes of acute stroke patients with atrial fibrillation.
AB  - Evaluation of: Kazumi K, Yasuyuki I, Kensaku S, Takeshi I, Shinji Y, Junya A. IV
      tPA therapy in acute stroke patients with atrial fibrillation. J. Neurol. Sci.
      276(1-2), 6-8 (2009). Stroke is the leading cause of disability and the second
      most common cause of death worldwide. The care and treatment of stroke patients
      have evolved over the last two decades, with increasing use of thrombolysis
      (e.g., intravenous tissue plasminogen activator in acute stroke patients), which
      has improved survival and recovery following stroke. The article under evaluation
      offers a greater insight into the relationship of clinical outcome of stroke and
      atrial fibrillation after tissue plasminogen activator infusion.

PMID- 19379060
TI  - Prasugrel in acute coronary syndrome patients undergoing percutaneous coronary
      intervention.
AB  - Currently, dual antiplatelet therapy with aspirin and clopidogrel represents the
      key treatment strategy for the prevention of ischemic events in patients with
      acute coronary syndrome (ACS) and/or undergoing percutaneous coronary
      intervention (PCI). However, there is a broad inter-individual response
      variability to such treatment strategy, and a considerable number of patients
      persist with inadequate platelet inhibition, which has been associated with an
      increased risk of ischemic events. Overall, these findings underscore the need
      for novel antiplatelet agents able to achieve greater platelet inhibition; this
      can potentially reduce ischemic event rates. Prasugrel (CS-747; LY 640315), a
      novel third-generation oral thienopyridine, is a specific, irreversible
      antagonist of the platelet adenosine diphosphate P2Y(12) receptor. Laboratory
      studies have shown prasugrel to be associated with more prompt, potent and
      predictable degrees of platelet inhibition compared with clopidogrel. In a large
      scale clinical study, which was comprised of high-risk ACS patients undergoing
      PCI, prasugrel was shown to significantly reduce the short- and long-term risk of
      ischemic events, including stent thrombosis. However, such significant reduction
      in ischemic events occurred at the expense of a higher risk of bleeding. Recent
      clinical trial data analyses have led to a better understanding of the efficacy
      and safety of prasugrel. This article reviews the currently available data
      regarding the efficacy and safety of prasugrel in ACS patients.

PMID- 19379062
TI  - Treatment of acute ischemic stroke: intravenous and endovascular therapies.
AB  - Stroke is the third most common cause of death in the USA, following heart
      disease and cancer. Intravenous recombinant tissue plasminogen activator is the
      only US FDA-approved pharmacological treatment available today for acute ischemic
      stroke. Despite the approval of this drug, it has been underutilized in the
      community. The limited time window of 3 h disqualifies many patients from
      receiving the drug. In addition, fears of intracranial hemorrhage have resulted
      in underutilization of the drug in the community setting. Efforts to increase the
      time window of treatment include utilization of the intra-arterial route for
      delivery of a thrombolytic drug and interventional mechanical strategies. In this
      article, we review the major intravenous and intra-arterial thrombolysis trials
      and review the mechanical strategies being developed to treat patients with acute
      ischemic stroke.

PMID- 19379063
TI  - Potential biomarkers for the diagnosis of stroke.
AB  - Stroke is common, with a high rate of disability and death, and current therapies
      are both highly time sensitive and carry some risk, making rapid diagnosis
      important. Many cases of stroke are difficult to diagnose clinically during the
      acute phase, and there are limitations to the ability of diagnostic imaging to
      help with the necessary speed. A reliable and valid biomarker would be invaluable
      for this common clinical situation, as it has been with myocardial infarction. A
      large number of molecules have been evaluated for this role, both in the
      laboratory and in patients, but the results to date have been disappointing. In
      this article, we review the operative concepts in the search for a diagnostic
      biomarker of stroke, a few of the promising candidates and the current challenges
      to validation.

PMID- 19379064
TI  - Racial/ethnic differences in poststroke rehabilitation utilization in the USA.
AB  - Longstanding racial/ethnic disparities exist in the USA in the areas of
      healthcare access, healthcare utilization and health-related outcomes of chronic
      health conditions, such as stroke. Regarding stroke specifically, significant
      racial/ethnic disparities in stroke incidence, severity and outcomes have been
      reported. Despite these differences, little attention has been given to potential
      racial/ethnic differences in the utilization of rehabilitation services for
      patients after stroke. To date, only a few studies have been specifically
      designed to examine racial/ethnic differences in rehabilitation service
      utilization. A review of these studies and related studies suggests that
      racial/ethnic differences may be present in the utilization of poststroke
      rehabilitation services. Consequently, new studies are needed to delineate how
      race/ethnicity influences utilization of poststroke rehabilitation services and
      to determine how a reduction in this disparity gap could improve stroke-related
      outcomes among racial/ethnic minorities in the USA.

PMID- 19379065
TI  - Impact of gender in patients with acute coronary syndrome.
AB  - In this article, we review the impact of gender on the pathophysiology,
      management and outcomes after acute coronary syndrome (ACS). We searched the
      English-language literature indexed in MEDLINE, Scopus and EBSCOhost Research
      databases from 1988 through January 2009 using the indexing terms 'gender',
      'short- and long-term outcomes' and 'acute coronary syndrome' and 'myocardial
      infarction'. Data comparing gender differences in outcomes after ACS showed that
      females have a higher mortality rate than males. Observational studies showed
      that guideline-recommended management strategies are used significantly less
      frequently in females than males. The undertreatment and worse outcome of female
      patients with ACS are probably multifactorial and have been reported in different
      ethnicities and cultures. However, there are conflicting data regarding to the
      impact of gender on early versus long-term outcomes, the benefit of early
      intervention in low- and high-risk females and the influence of unmeasured
      selection biases in the use of therapies in the observational data. These gender
      discrepancy trends warrant close follow-up, as this might reflect changes in
      primary and secondary prevention in the community. Furthermore, gender
      discrepancy gives an indication of healthcare quality and whether care is given
      in an unbiased manner. All high-risk females, and males with ACS, should receive
      optimal medical management, coronary angiography and revascularization whenever
      indicated.

PMID- 19379066
TI  - Management of hypertension in chronic heart failure.
AB  - Chronic heart failure (CHF) is associated with frequent hospitalizations and high
      mortality. It affects more than 5 million individuals in the USA, and another
      660,000 new cases are diagnosed each year; overall, heart failure (HF) now
      accounts for 7% of all deaths from cardiovascular disease. Hypertension (HTN)
      increases the risk of development of HF and it precedes it in 75% of cases. HF
      patients are nearly evenly divided between those with reduced left ventricular
      (LV) function or systolic dysfunction and those with preserved LV systolic
      function or diastolic dysfunction. The management of HTN in patients with CHF is
      challenging. Drugs such as beta-blockers, angiotensin-converting enzyme
      inhibitors, angiotensin receptor blockers, aldosterone receptor blockers,
      hydralazine and nitrates, which have shown mortality benefit in CHF and exert
      antihypertensive effects, should be used as first-line agents to control HTN in
      CHF. In addition, antihypertensive drugs such as alpha-receptor blockers that can
      increase mortality in HF should be avoided. The dihydropyridine group of calcium
      channel blockers are good antihypertensive medications with a neutral effect on
      mortality in patients with CHF. These may be used in CHF patients with refractory
      HTN. In patients with HF with reduced ejection fraction, HTN is treated
      differently in comparison to patients with HF with normal ejection fraction. This
      article reviews the treatment of essential HTN in patients at risk for developing
      HF, in the presence of HF and the latest developments in treatment that might
      benefit both HTN and HF management.

PMID- 19379068
TI  - Modern imaging of the infarct core and the ischemic penumbra in acute stroke
      patients: CT versus MRI.
AB  - Thrombolysis has become an approved therapy for acute stroke. However, many
      stroke patients do not benefit from such treatment, since the presently used
      criteria are very restrictive, notably with respect to the accepted time window.
      Even so, a significant rate of intracranial hemorrhage still occurs. Conventional
      cerebral computed tomography (CT) without contrast has been proposed as a
      selection tool for acute stroke patients. However, more-modern MRI and CT
      techniques, referred to as diffusion- and perfusion-weighted imaging and
      perfusion-CT, have been introduced, which afford a comprehensive noninvasive
      survey of acute stroke patients as soon as their emergency admission, with
      accurate demonstration of the site of arterial occlusion and its hemodynamic and
      pathophysiological repercussions for the brain parenchyma. The objective of this
      article is to present the advantages and drawbacks of CT and MRI in the
      evaluation of acute stroke patients.

PMID- 19379070
TI  - Chemotaxis-like regulatory systems: unique roles in diverse bacteria.
AB  - Bacteria sense the chemical world using a variety of mechanisms that include the
      frequently described two-component system (TCS), which comprises a sensor kinase
      and response regulator, to regulate gene expression in response to environmental
      cues. One of the best and most widely studied versions of the TCS is the system
      that controls chemotaxis in Escherichia coli. The chemotaxis machinery includes
      components not found in other TCS to regulate motility and is therefore an
      exception to the rule for two-component signaling. The hallmark feature of the
      chemotaxis system is the presence of an adaptation module in which the sensor
      receptor protein is posttranslationally modified to attenuate ligand-induced
      signaling, a mechanism not yet identified for the more widely distributed
      prototypical TCS. More recently, variations on the chemotaxis system itself have
      been identified and they are termed chemosensory systems and are the subject of
      this review. Extensive research has provided a perspective on TCS signaling and
      indicates that variation and diversity for the standard two-component system are
      predominant in the microbial world.

PMID- 19379069
TI  - Aminoacyl-tRNA synthesis and translational quality control.
AB  - Translating the 4-letter code of RNA into the 22-letter alphabet of proteins is a
      central feature of cellular life. The fidelity with which mRNA is translated
      during protein synthesis is determined by two factors: the availability of
      aminoacyl-tRNAs composed of cognate amino acid:tRNA pairs and the accurate
      selection of aminoacyl-tRNAs on the ribosome. The role of aminoacyl-tRNA
      synthetases in translation is to define the genetic code by accurately pairing
      cognate tRNAs with their corresponding amino acids. Synthetases achieve the amino
      acid substrate specificity necessary to keep errors in translation to an
      acceptable level in two ways: preferential binding of the cognate amino acid and
      selective editing of near-cognate amino acids. Editing significantly decreases
      the frequency of errors and is important for translational quality control, and
      many details of the various editing mechanisms and their effect on different
      cellular systems are now starting to emerge.

PMID- 19379077
TI  - Carrier analysis for hemophilia A: ideal versus acceptable.

PMID- 19379078
TI  - Vascular biomarkers in the metabolic syndrome.

PMID- 19379079
TI  - Mea Culpa with cancer-targeted therapy: new thinking and new agents design for
      novel, causal networks-based, personalized biomedicine.

PMID- 19379081
TI  - Personalized cancer diagnostics and therapeutics.

PMID- 19379082
TI  - mTOR in renal cell cancer: modulator of tumor biology and therapeutic target.
AB  - Elucidation of the crucial role of the PI3K/Akt/mTOR pathway in the pathogenesis
      of cancer has led to the development of various drugs targeting this signaling
      cascade at distinct levels. mTOR, a serine/threonine kinase plays a pivotal role
      in coupling growth stimuli to cell cycle progression. There are two distinct
      macromolecular complexes of mTOR: mTORC1, which is rapamycin-sensitive and
      contains raptor; and mTORC2, which is rapamycin-insensitive and contains rictor.
      However, in recent preclinical studies a sustained exposure of cancer cells to
      rapamycin has been shown to inhibit the function of both mTORC1 and mTORC2
      complexes. Downstream targets of these complexes, which involve HIF-1alpha and
      HIF-2alpha, cyclin D1 and PKC-alpha, are responsible for the activation of
      various intracellular processes leading to the activation of cell proliferation,
      and induction of angiogenesis, metastasis or chemoresistance. Since the biology
      of renal cell cancer (RCC) is tightly controlled by mTOR, targeted inhibition of
      mTOR function appeared to be a promising therapeutic approach for RCC patients.
      To date, results of two, large, Phase III clinical trials evaluating the efficacy
      of rapamycin derivatives (i.e., temsirolimus and everolimus) in the treatment of
      RCC have been published. First-line temsirolimus (CCI-779) administered to
      metastatic, poor-prognosis RCC patients significantly prolonged overall and
      progression-free survival when compared with IFN-alpha. Treatment of metastatic
      RCC patients refractory to tyrosine kinase inhibitors with everolimus (RAD-001)
      significantly prolonged progression-free survival when compared with placebo.
      Therapeutic strategies based on mTOR inhibition in RCC demonstrated a significant
      clinical activity. However, there are still patients refractory to mTOR
      inhibitors. Various molecular mechanisms of resistance to rapalogues have been
      identified and will have to be targeted simultaneously with mTOR in order to
      achieve a complete inhibition of signaling pathways crucial for the pathogenesis
      of RCC. Such clinical trials evaluating a combination of mTOR inhibitors with
      other targeted therapies are ongoing.

PMID- 19379084
TI  - Epigenetic biomarkers in urothelial bladder cancer.
AB  - Bladder cancers comprise heterogeneous cell populations, and numerous factors are
      likely to be involved in dictating recurrence, progression and patient survival.
      While several molecular markers that are used to evaluate the development and
      prognosis of bladder cancer have been studied, the limited value of these
      established markers has created the need for new molecular indicators of bladder
      cancer prognosis. Of particular interest is the silencing of tumor-suppressor
      genes by epigenetic alteration. Recent progress in understanding epigenetic
      modification and gene silencing has led to new opportunities for the
      understanding, detection, treatment and prevention of cancer. Moreover,
      epigenetic silencing of tumor-suppressor genes is interesting from a clinical
      standpoint, because of the possibility of reversing epigenetic changes and
      restoring gene function in a cell. This review focuses on the prognostic
      relevance of epigenetic markers in bladder cancer.

PMID- 19379085
TI  - Blood-based transcriptomics: leukemias and beyond.
AB  - In 1999, Golub et al. proposed for the first time microarray-based
      transcriptional profiling to be used as a new technology for the differential
      diagnosis of acute myeloid leukemias and acute lymphocytic leukemias. This very
      preliminary study sparked great enthusiasm beyond the leukemias. Over the last 10
      years, numerous studies addressed the use of gene expression profiling of
      peripheral blood from patients with malignancies, infectious diseases,
      autoimmunity and even cardiovascular diseases. Despite this great effort, no
      single test has yet been established using microarray-based transcriptional
      profiling of peripheral blood. Here we highlight the advances in the field of
      blood transcriptomics during the last 10 years and also critically discuss the
      issues that need to be resolved before blood transcriptomics will become part of
      daily diagnostics in the leukemias, as well as in other diseases showing
      involvement of peripheral blood.

PMID- 19379083
TI  - DNA methylation changes in prostate cancer: current developments and future
      clinical implementation.
AB  - Promoter hypermethylation is associated with the loss of expression of tumor
      suppressor genes in cancer. Currently, several genome-wide technologies are
      available and have been utilized to examine the extent of DNA methylation in
      discovery-based studies involving several physiological and disease states.
      Although early in the process, aberrant DNA methylation is gaining strength in
      the fields of cancer risk assessment, diagnosis and therapy monitoring in
      different cancer types. There is a need to improve existing methods for early
      diagnosis of prostate cancer and to identify men at risk for developing
      aggressive disease. Because of the ubiquity of DNA methylation changes and the
      ability to detect methylated DNA in several body fluids (e.g., blood and urine),
      this specifically altered DNA may serve, on one hand, as a possible new screening
      marker for prostate cancer and, on the other hand, as a tool for therapy
      monitoring in patients having had neoplastic disease of the prostate. Since many
      prostate cancer patients present with advanced disease and some present with
      nonspecific elevation of prostate-specific antigen without prostate cancer, early
      detection with high specificity and sensitivity is considered to be one of the
      most important approaches to reduce mortality and unwanted tension of the men
      with high prostate-specific antigen. Therefore, an effective screening test would
      have substantial clinical benefits. Furthermore, methylation markers of risk of
      progression of disease in patients having prostate cancer permits immediate
      commencement of specific treatment regimens and probably longer survival and
      better quality of life. This review illustrates the current benefits and
      limitations of potentially useful prostate cancer methylation markers that have
      considerable existing data and touches upon other future markers as well as the
      field of methylation in prostate cancer.

PMID- 19379086
TI  - Recent perspectives on the genetic background of neural tube defects with special
      regard to iniencephaly.
AB  - Iniencephaly is a rare and mostly lethal type of neural tube defect. The pattern
      of inheritance of this group of malformations is multifactorial, rendering the
      identification of the underlying causes. Numerous studies have been conducted to
      elucidate the genetic basis of human neurulation. Essential signaling pathways of
      the development of the CNS include the planar cell polarity pathway, which is
      important for the initiation of neural tube closure, as well as the sonic
      hedgehog pathway, which regulates the neural plate bending. Genes influencing the
      different stages of neurulation have been investigated for their eventual role in
      the development of these malformations. Among the environmental factors, folic
      acid seems to be the most important modifier of the risk of human neural tube
      defects. Genes of the folate metabolism pathways have also been investigated to
      identify mutations resulting in increased risk of neural tube defects. In this
      review we have attempted to summarize the knowledge on iniencephaly and neural
      tube defects, with special regard to genetic factors of the etiology.

PMID- 19379089
TI  - Identity style in patients with borderline personality disorder and normal
      controls.
AB  - Identity diffusion is one of the essential diagnostic criteria for borderline
      personality disorder. Diffuse-avoidant identity style (as conceptualized by
      Berzonsky, 1989), diffuse identity status (as conceptualized by Marcia, 1966) and
      Structural identity diffusion (as conceptualized by Erikson, 1959; Kernberg,
      1984, 2006; and Akhtar, 1992), are theoretically and to some extent empirically
      related. In this study, identity style in a group of female borderline patients
      (n = 66), measured by using the Identity Style Inventory (ISI) developed by
      Berzonsky, was compared with identity style in a control group of female
      psychology students (n = 65). Findings revealed that the mean score for diffuse
      avoidant identity style was significantly higher in the borderline group: more
      than half the borderline patients (59%) were classified as primarily diffuse
      avoidant in identity style, compared with only 12% in the control group.
      Similarly, ISI-scores for the more mature and more adaptive information-oriented
      identity style and for the normative identity style were significantly higher in
      the control group compared with the group of borderline patients. Finally, the
      level of commitment in identity functioning was significantly lower in the
      borderline group than in the group of psychology students.

PMID- 19379090
TI  - Defense mechanisms associated with borderline personality disorder.
AB  - This study assessed the defensive functioning of 290 criteria-defined borderline
      patients and compared it to that of 72 patients with other forms of axis II
      psychopathology. The Defense Style Questionnaire (DSQ), a self-report measure
      with demonstrated criterion validity and internal consistency, was administered
      to 362 axis II inpatients diagnosed using semistructured interviews of proven
      reliability. Borderline patients had significantly higher scores than axis II
      comparison subjects on three of the four defense styles assessed by the DSQ: self
      sacrificing, maladaptive action, and image-distorting defenses. They also had
      significantly higher scores than axis II comparison subjects on eight of the 19
      defense mechanisms studied. More specifically, borderline patients had
      significantly higher scores on one neurotic-level defense (undoing), four
      immature defenses (acting out, emotional hypochondriasis, passive aggression, and
      projection), and two image-distorting/borderline defenses (projective
      identification and splitting). In contrast, axis II comparison subjects had a
      significantly higher score than borderline patients on one mature defense
      (suppression). When all significant defenses were considered together, three were
      found to be significant predictors of a borderline diagnosis: acting out,
      emotional hypochondriasis, and undoing. This model has both good sensitivity
      (.95) and positive predictive power (.86). Taken together, the results of this
      study suggest that the defensive profile of borderline patients is distinct from
      that of patients with other forms of axis II pathology. They also suggest that
      the defensive triad of acting out, emotional hypochondriasis, and undoing may
      serve as a useful clinical marker for the borderline diagnosis, particularly in
      settings where the base rate of the disorder is high.

PMID- 19379091
TI  - Temperament as a prospective predictor of self-injury among patients with
      borderline personality disorder.
AB  - This study examined the association of novelty seeking, harm avoidance, and
      reward dependence with different types (suicide attempts vs. nonsuicidal self
      injury) and aspects (medical risk, impulsiveness, suicide intent) of self-injury
      over a 12-month period. Fifty-five female patients with borderline personality
      disorder enrolled in clinical trials completed Cloninger's Temperament and
      Character Inventory at pretreatment as well as the Suicide Attempt Self-Injury
      Interview at four-month intervals starting from the pretreatment assessment.
      Regression analyses indicated that the reward dependence subscale of attachment,
      a protective factor, was most consistently and uniquely associated with aspects
      of self-injury, including prestudy and prospective nonsuicidal self-injury and
      suicide intent, and prospective suicide attempts. After controlling for prestudy
      self-injury, few temperament variables predicted prospective self-injury. Higher
      scores on both the novelty seeking subscale of impulsiveness and the reward
      dependence attachment subscale were associated with lower prospective suicide
      intent even after controlling for pre-study suicide intent.

PMID- 19379092
TI  - Attentional bias to personally relevant words in borderline personality disorder
      is strongly related to comorbid posttraumatic stress disorder.
AB  - Current research indicates altered inhibitory functioning in borderline
      personality disorder (BPD). The emotional stroop task is a widely used method for
      investigating inhibition of interference. In the present study we used an
      individualized version of the emotional stroop task to investigate inhibitory
      functioning in BPD with respect not only to valence but also to personal
      relevance of the stimuli. Thirty-one BPD patients and 49 healthy controls
      performed the individual emotional stroop task that consisted of (1) words
      related to personal negative life events that were currently relevant (2) words
      related to personal negative life events that were not currently relevant, (3)
      negative words that were not personally relevant, and (4) neutral words. BPD
      patients showed greater interference only for words related to personal negative
      life events with current relevance. A comparison between BPD patients with and
      without posttraumatic stress disorder (PTSD) revealed reduced inhibitory
      functioning only in BPD patients with PTSD. Inhibition of interference in BPD
      patients seems not to be altered in general but is exclusively disturbed in those
      with comorbid PTSD when highly relevant personal factors are the focus of
      attention.

PMID- 19379093
TI  - Meta-analyses of mood stabilizers, antidepressants and antipsychotics in the
      treatment of borderline personality disorder: effectiveness for depression and
      anger symptoms.
AB  - The objective of our study was to complete separate meta-analyses of randomized
      controlled trials of mood stabilizers, antidepressants and antipsychotics to
      determine whether these medications are efficacious for depression and anger
      symptoms in borderline personality disorder (BPD). Studies were obtained from
      OVID Medline, Cochrane Central Register of Controlled Trials, and PsychInfo.
      References of all original papers and reviews were searched for additional
      studies. Index terms included: BPD, randomized controlled trials, drug therapy,
      medication, and treatment. Studies were included if they were randomized double
      blind placebo-controlled trials, published in a peer reviewed journal, had a
      majority of patients with BPD or included patients with BPD where anger was a
      target of treatment. Preference was given to studies using outcome measures that
      were well known, validated, objective, and based on intent-to-treat data. Where
      available, measures of anger that incorporated verbal and other indirect forms of
      aggression were utilized. The StatsDirect meta-analysis program was used to
      calculate an effect size and 95% confidence interval for each study. Mood
      stabilizers, with the exception of divalproic acid, were found to have a large
      pooled effect size (-1.75, 95% CI = -2.77 to -0.74) for anger. Divalproic acid
      and carbamazepine had a moderate effect on depression. Antidepressants had a
      moderate effect on anger reduction, but a small effect on depression.
      Antipsychotics had a moderate effect on anger; however aripiprazole had a much
      larger effect-size than other antipsychotics. Antipsychotics did not have an
      effect for depression. Sources of variation between studies included length of
      treatment (5-24 weeks), drop out rates (5% to 65%), proportion of patients in
      psychotherapy (0-100%) and with comorbid mood disorders (0-100%). Unfortunately
      most studies excluded patients with alcohol and substance abuse, suicidality, and
      self-harm behaviors. This may limit the ability to generalize our findings to
      usual clinical practice.

PMID- 19379094
TI  - A cross-cultural study of the higher-order structures underlying personality
      disorders in French-speaking Africa and Switzerland.
AB  - Most studies about the higher-order dimensions to be considered in order to
      parsimoniously describe Personality Disorders (PDs) have identified between two
      and four factors but there is still no consensus about their exact number. In
      this context, the cultural stability of these structures might be a criterion to
      be considered. The aim of this study was to identify stable higher-order
      structures of PD traits in a French-speaking African and Swiss sample (N =
      2,711). All subjects completed the IPDE screening questionnaire. Using Everett's
      criterion and conducting a series of principal component analyses, a cross
      culturally stable two- and four-factor structure were identified, associated with
      a total congruence coefficient of .98 and .94, respectively, after Procrustes
      rotation. Moreover, these two structures were also highly replicable across the
      four African regions considered, North Africa, West Africa, Central Africa, and
      Mauritius, with a mean total congruence coefficient of .97 and .87, respectively.
      The four-factor structure presented the advantage of being similar to Livesely's
      four components and of describing the ten PDs more accurately.

PMID- 19379095
TI  - The age distribution of self-reported personality disorder traits in a household
      population.
AB  - Stability over time is an essential criterion for the diagnosis of a personality
      disorder (PD) according to DSM-IV and ICD-10. However, both longitudinal and
      cross-sectional studies have demonstrated considerable changes of personality
      disorder traits during life-span, an observation which challenges this
      assumption. We measured self-reported DSM-IV personality disorder traits in a
      nationally representative community sample using a cross-sectional design. We
      investigated the association of dimensional PD scores with age. Our analyses
      confirmed a decreasing prevalence of personality disorder mean scores across age
      groups in the population, particularly Cluster B, with an increase in self
      reported schizoid and obsessive-compulsive scores. Furthermore, specific
      interactions of demographic characteristics and age were identified. Analyses of
      transition points in the distribution of personality disorders across different
      age groups did not demonstrate increasing stability after age 30 as previously
      observed for normal personality traits. Significant changes occurred primarily
      after the third decade.

PMID- 19379096
TI  - Dimensions of psychopathy in relation to suicidal and self-injurious behavior.
AB  - Externalizing psychopathology is associated with an increased risk for suicidal
      behavior. Within the externalizing domain, psychopathy may be an important
      construct for the understanding of which individuals are at particularly high
      risk. However, prior studies of psychopathy and suicidal behavior have not
      distinguished between suicide attempts and nonsuicidal self-injurious behavior
      (NSIB). The present study used data on 810 civil psychiatric patients from the
      MacArthur Violence Risk Assessment Project to examine the relationships between
      scores on the four dimensions of the Psychopathy Checklist: Screening Version
      (PCL: SV) and suicide attempts and nonsuicidal self-injurious behavior (NSIB).
      Results indicate that only the antisocial dimension of psychopathy is associated
      with suicide attempts. With regard to NSIB, an interaction was found such that,
      among African-Americans, NSIB was more prevalent at higher levels of
      antisociality. Present findings refine previous results from studies using the
      two-factor PCL:SV model and have important implications for the assessment of
      suicide risk.

PMID- 19379097
TI  - New approaches to decontamination of rooms after patients are discharged.

PMID- 19379098
TI  - Comparison of the efficacy of a hydrogen peroxide dry-mist disinfection system
      and sodium hypochlorite solution for eradication of Clostridium difficile spores.
AB  - OBJECTIVE: To compare a hydrogen peroxide dry-mist system and a 0.5% hypochlorite
      solution with respect to their ability to disinfect Clostridium difficile
      contaminated surfaces in vitro and in situ. DESIGN: Prospective, randomized,
      before-after trial. SETTING: Two French hospitals affected by C. difficile.
      INTERVENTION: In situ efficacy of disinfectants was assessed in rooms that had
      housed patients with C. difficile infection. A prospective study was performed at
      2 hospitals that involved randomization of disinfection processes. When a patient
      with C. difficile infection was discharged, environmental contamination in the
      patient's room was evaluated before and after disinfection. Environmental
      surfaces were sampled for C. difficile by use of moistened swabs; swab samples
      were cultured on selective plates and in broth. Both disinfectants were tested in
      vitro with a spore-carrier test; in this test, 2 types of material, vinyl
      polychloride (representative of the room's floor) and laminate (representative of
      the room's furniture), were experimentally contaminated with spores from 3 C.
      difficile strains, including the epidemic clone ribotype 027-North American
      pulsed-field gel electrophoresis type 1. RESULTS: There were 748 surface samples
      collected (360 from rooms treated with hydrogen peroxide and 388 from rooms
      treated with hypochlorite). Before disinfection, 46 (24%) of 194 samples obtained
      in the rooms randomized to hypochlorite treatment and 34 (19%) of 180 samples
      obtained in the rooms randomized to hydrogen peroxide treatment showed
      environmental contamination. After disinfection, 23 (12%) of 194 samples from
      hypochlorite-treated rooms and 4 (2%) of 180 samples from hydrogen peroxide
      treated rooms showed environmental contamination, a decrease in contamination of
      50% after hypochlorite decontamination and 91% after hydrogen peroxide
      decontamination (P < .005). The in vitro activity of 0.5% hypochlorite was time
      dependent. The mean (+/-SD) reduction in initial log(10) bacterial count was 4.32
      +/- 0.35 log(10) colony-forming units after 10 minutes of exposure to
      hypochlorite and 4.18 +/- 0.8 log(10) colony-forming units after 1 cycle of
      hydrogen peroxide decontamination. CONCLUSION: In situ experiments indicate that
      the hydrogen peroxide dry-mist disinfection system is significantly more
      effective than 0.5% sodium hypochlorite solution at eradicating C. difficile
      spores and might represent a new alternative for disinfecting the rooms of
      patients with C. difficile infection.

PMID- 19379099
TI  - Outbreak of Pseudomonas aeruginosa infection associated with contamination of a
      flexible bronchoscope.
AB  - BACKGROUND: A cluster of patients with respiratory cultures positive for
      Pseudomonas aeruginosa with a unique antibiogram was observed during June and
      July 2007 at a 1,000-bed urban teaching hospital in Atlanta, Georgia. These P.
      aeruginosa isolates were recovered from bronchoscopically obtained specimens.
      METHODS: A cross-sectional study was performed to assess whether the cluster was
      associated with exposure to a particular bronchoscope (B1); cultures from
      specimens from the bronchoscopes and the environment were obtained, and the P.
      aeruginosa isolate type was determined using pulsed-field gel electrophoresis
      (PFGE). Records of patients exposed to B1 during the cluster period were
      reviewed. RESULTS: Twelve patients with a culture positive for P. aeruginosa with
      the unique susceptibility pattern were identified in June-July 2007. No cases
      were documented from March 1 through May 31, 2007. Culture specimens obtained
      from B1 after high-level disinfection revealed P. aeruginosa, prompting removal
      of B1 from service on July 23, 2007. No cases occurred after that date. Eleven
      (55%) of 20 patients who were exposed to B1 during the cluster period had a
      culture positive for P. aeruginosa, compared with 1 (2%) of 53 patients who were
      exposed to other bronchoscopes (P < .001). PFGE patterns for P. aeruginosa
      isolates obtained from case patients and from B1 were identical. An engineering
      evaluation of B1 documented several internal damages. Two (10.5%) of 19 patients
      exposed to B1 during the cluster period may have developed P. aeruginosa
      infection following exposure to B1. CONCLUSIONS: An outbreak or pseudo-outbreak
      of P. aeruginosa infection occurred in association with use of a damaged
      bronchoscope. Periodic engineering maintenance may be needed to prevent
      bronchoscope contamination that is resistant to high-level disinfection.

PMID- 19379101
TI  - Robert P. Kadlec, MD, former Special Assistant to the President and Senior
      Director for Biodefense Policy, Homeland Security Council. Interview by Madeline
      Drexler.

PMID- 19379102
TI  - The legal landscape for school closures in response to pandemic flu or other
      public health threats.
AB  - Together with other nonpharmaceutical interventions in response to pandemic
      influenza or other public health emergencies, communitywide closure of schools
      (grades K-12) for up to several weeks may mitigate the impacts of pandemic flu or
      other public health threats across populations. Though debatable, the public
      health premise is that closing schools could limit the spread of influenza (or
      other communicable conditions), consistent with social distancing theories. This
      presumes that laws support school closures for extended time periods during each
      wave of an influenza pandemic. However, government agencies and others have
      incomplete and inconsistent information about whether laws authorize long-term
      school closure for public health purposes in routine and emergency circumstances.
      As a result, the Centers for Law and the Public's Health: A Collaborative at
      Johns Hopkins and Georgetown Universities examined laws that expressly authorize
      school closure due to pandemic flu or other public health threats in 52 U.S.
      jurisdictions. While school closure is legally possible in most jurisdictions
      during routine and emergency circumstances, significant legal issues remain. When
      can schools be closed for public health purposes, and under what standards? Which
      levels and departments of government are actually responsible for closing
      schools? How does an emergency declaration affect government authority to close
      schools? This article explains the Center's study methodology, presents major
      findings on express laws allowing for school closure, and discusses legal issues
      underlying school closures during nonemergencies and declared emergencies.

PMID- 19379103
TI  - Update on emergency liability protection for volunteer entities.

PMID- 19379104
TI  - Early warning infectious disease surveillance.
AB  - The Early Warning Infectious Disease Surveillance program (EWIDS) is part of the
      Cooperative Agreement on Public Health Preparedness and Response for Bioterrorism
      administered by the Centers for Disease Control and Prevention (CDC). The purpose
      of EWIDS is to develop and implement a program to collaborate with states or
      provinces across international borders, to provide rapid and effective laboratory
      confirmation, and to expand surveillance capabilities. Prior to September 11,
      2001, funds were not allocated to states for improving cross-border epidemiologic
      and laboratory surveillance activities that would increase cross-border
      preparedness. States were required through the Cooperative Agreement to self
      report data twice a year in progress reports to the Division of State and Local
      Readiness Management Information System (MIS). An analysis of self-reported
      activities was conducted to determine the activities that states most frequently
      chose to implement based on existing public health infrastructure along the U.S.
      borders, since analysis of preparedness activities on the border has not
      previously been conducted. This article discusses how states chose to address
      expanding infrastructure capacity with the EWIDS supplemental funding, the
      challenges that have prevented U.S. border states from addressing all suggested
      activities, and the importance of sustained funding for the investment of
      continued capacity building and collaboration with international partners.

PMID- 19379105
TI  - Biosecurity policies at international life science journals.
AB  - The prospect of bioterrorism has raised concerns about the potential abuse of
      scientific information for malign purposes and the pressure on scientific
      publishers to prevent the publication of "recipes" for weapons of mass
      destruction. Here we present the results of a survey of 28 major life science
      journals--20 English-language international journals and 3 Chinese and 5 Russian
      journals--with regard to their biosecurity policies and procedures. The survey
      addressed the extent to which life science journals have implemented biosecurity
      procedures in recent years, how authors and reviewers are advised about these
      procedures and the underlying concerns, and what the practical experiences have
      been. Few of the English-language publishers and none of the Russian and Chinese
      publishers surveyed implement formal biosecurity policies or inform their authors
      and reviewers about potentially sensitive issues in this area.

PMID- 19379106
TI  - Biodefense and public health preparedness in Virginia.
AB  - Since 2001, much research has examined national- and state-level preparedness
      against bioterrorism or naturally occurring epidemics. Few studies, however, have
      adequately addressed preparedness at the local level, and research to date
      indicates the difficulty of accurately assessing preparedness at any level. This
      study examined preparedness across the 35 health districts of Virginia in 4
      defined categories of preparedness: personnel, services, technology, and
      emergency preparedness. Preparedness indicators were examined with respect to
      demographic, geographic, and critical infrastructure characteristics at the
      county and city levels. In all 4 categories of preparedness, the models obtained
      statistically significant results relating factors of demography, geography, and
      critical infrastructure to higher or lower levels of preparedness across
      Virginia. This study presents a methodology for public health researchers who
      wish to determine the preparedness of local health districts across the United
      States. It is intended that the combination of such research, based on local
      data, with larger, more general studies will paint a more accurate and
      constructive picture of preparedness.

PMID- 19379107
TI  - PrepLink: a novel web-based tool for healthcare emergency planning and response.
AB  - Effective planning and response to bioterrorism or other disasters, natural or
      manmade, requires timely and effective communication as well as situational
      awareness. During a catastrophic event, decision makers--including first
      responders, hospital workers, and command center emergency workers--will have a
      short time to make crucial decisions. Preparing to receive and treat patients,
      especially when there are mass casualties, requires immediate access to large
      amounts of integrated health data from disparate sources. This article describes
      PrepLink, a novel comprehensive web-based healthcare-related all-hazards
      electronic disaster management system. Over the past 3 years, PrepLink has been
      developed and tested at the University of Pittsburgh Medical Center in
      partnership with the Pennsylvania National Guard. It can be deployed in multiple
      sites across a region or state or more broadly. The system includes pages for
      public awareness about planning for and responding to disasters, as well as
      secure, password-protected private pages that can be used by many types of
      emergency and healthcare personnel who are involved in such events. Timely
      information related to public health, safety, planning, preparation, and response
      can be accessed from both sets of pages. The system permits rapid communication
      and sharing of team plans across disparate locations; it stores multiple key
      documents and contains asset inventories, a GIS, patient tracking, and a command
      and-control module. Each function is directly related to providing healthcare
      treatment for victims. PrepLink's comprehensive and user friendly approach to
      health-related disaster management holds promise for future progress in this
      challenging arena.

PMID- 19379108
TI  - Sustaining progress in the life sciences: strategies for managing dual use
      research of concern--progress at the national level.

PMID- 19379109
TI  - Maximizing state and local medical countermeasure stockpile investments through
      the Shelf-Life Extension Program.

PMID- 19379110
TI  - Probabilistic risk analysis and bioterrorism risk.

PMID- 19379112
TI  - Evaluation of clinical practice improvement programs for nurses for the
      management of alcohol withdrawal in hospitals.
AB  - The most common alcohol-related chronic condition for hospitalisation is alcohol
      dependence which can lead to an alcohol withdrawal syndrome (AWS). The aim of
      this paper is to report on a quality improvement program in an Australian rural
      area health service for the screening and management of alcohol withdrawal and
      the effect of two types of nursing education and training approaches: a self
      directed competency training package and a more traditional in-service program.
      The measure of improvement was compliance to nine clinical standards or core
      competencies for the assessment and treatment of the AWS derived from the
      Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale and
      the NSW drug and alcohol withdrawal clinical practice guidelines. An audit of
      medical records using a standardised protocol for the nine standards was
      conducted at baseline (n=100) and follow-up (n=340) across eleven hospitals in
      the area. Results indicated that in three hospitals, where 70 nurses completed
      the self-directed competency training, there was a higher total compliance score
      across the nine standards compared to eight hospitals where 238 nurses received
      the in-service program. The self-directed competency program was also rated
      highly by nurses who participated in the program. The benefits of self-directed
      competency training are discussed as well as future recommendations for improving
      nurse education strategies for managing alcohol withdrawal.

PMID- 19379113
TI  - Nurses in abortion care: identifying and managing stress.
AB  - The psychological impact of abortion on the women undergoing the procedure is
      well researched, but little is known about the potential psychological impact on
      nurses working in abortion care. The proportion of medical abortions in the UK is
      rising compared to surgical abortions. A recent research study found that being
      more directly involved in the procedure places more emotional demands on the
      nurses. This emotional labour required by nurses working in abortion care may
      increase their stress levels. This paper examines the potential increase in
      stress in nurses caused by medical abortions. A model of stress comprising
      stressors, moderators and stress outcomes was used as a framework for this
      examination. Research on abortion and mental health nursing was applied to
      managing stress in abortion care; this included coping mechanisms, prevention and
      intervention strategies. This showed that stress, burnout and coping are
      important issues in abortion care. On this basis, recommendations for practice
      have been formulated to inform practice for nurses and managers in abortion care.

PMID- 19379114
TI  - Factors affecting compliance with eye drop therapy for glaucoma in a
      multicultural outpatient setting.
AB  - Ophthalmic nurses at Sydney Hospital Sydney Eye Hospital aimed to assess and
      evaluate the knowledge and resulting behaviours of patients using eye drop
      therapy for glaucoma and the effect that using interpreters or English speaking
      family members had on patients' understanding and compliance. Non-compliance is
      known to lead to progression of the disease with resulting loss of vision. The
      study showed that patients undergoing long-term therapy for glaucoma have areas
      of non-compliance that may not be apparent to staff who see them in a clinic
      setting. It also showed that ineffectual use or missed doses of eye drops occur
      in both male and female groups, young and older groups and those from non-English
      and English speaking backgrounds. This is in spite of the same patients'
      assurances that they have received clear instructions. It has been shown that the
      use of interpreters or English speaking family members has not affected
      compliance. This study has shown that even patients who have been on therapy for
      over 12 months are likely to benefit from continuing education and reinforcement
      of good technique. Poor understanding of glaucoma in the over 65 age group was
      not associated with a higher rate of non-compliance.

PMID- 19379115
TI  - The expectations of two New Zealand health services of the role of Clinical
      Chairs in Nursing and Midwifery.
AB  - Clinical Professoriate positions within nursing or midwifery in New Zealand are a
      relatively recent development. One New Zealand University worked collaboratively
      to establish two joint clinical Professorial appointments with different District
      Health Boards. Each position had unique mandates around research platforms, and
      differing operational responsibilities. This paper reports on the qualitative
      component of a larger study that aimed to examine the research culture, and the
      role of Clinical Chairs, within the two District Health Boards. This phase of the
      research involved semi-structured interviews with senior staff from the DHB to
      explore their experiences of working with the Clinical Professor. Themes that
      emerged revolved around expectations of the role during its development, and the
      subsequent perceived outcomes. The need for objective measures of the roles'
      impact on clinical outcomes emerged as a key impression from the participants.
      Future research that focuses on measurements of outcomes attributable to the
      roles will ensure their sustainability over time.

PMID- 19379116
TI  - Graduate nurses experiences of developing trust in the nurse-patient
      relationship.
AB  - This paper presents the findings of a qualitative exploratory descriptive study
      that aimed to explore and describe graduate nurses' perceptions and experiences
      of establishing trust in the nurse-patient relationship. Trust has been
      identified in the literature to be a crucial element in establishing an effective
      nurse- patient relationship. There is little in the literature, however, about
      the development of trust in the new graduate nurse-patient relationship. This
      research attempts to address this deficit. With this in mind, in depth interviews
      were conducted with seven first year registered nurses participating in graduate
      year programs. These first year nurses were asked to describe what their
      knowledge, understanding and experience of trust was in the nurse-patient
      relationship. From the data the themes that emerged were building a rapport,
      communication, being professional and confidence. The results of this study
      indicate that before a graduate nurse can achieve a trusting relationship with a
      patient, they first have to develop a rapport with them. More emphasis,
      therefore, on teaching communication skills in undergraduate and graduate
      programs may help to increase the knowledge and skills of new graduate nurses. In
      addition, including discussions on the factors that are important to building
      rapport and trust, what being a professional entails and strategies for caring
      for patients in situations where rapport has not been achieved. This research was
      undertaken as part of a Bachelor of Nursing Honors program.

PMID- 19379117
TI  - Uncovering knowing in practice during the graduate year: an exploratory study.
AB  - Becoming a graduate nurse is both a complex and stressful transition. Graduates
      must socialise into the context of nursing practice while developing their own
      clinical expertise and knowledge as novice registered nurses. This paper
      describes a study that explored graduate nurses' development of knowing and
      reflectivity during their graduate programs. This study used a series of audio
      taped focus groups and anecdotes collected from participants during the first
      eighteen months of being a nurse. Anecdotes were submitted as word files,
      electronically to the chief researcher and thematically analysed using Carper's
      (1978) ways of knowing as a framework. Four ways of knowing were identified
      through the anecdotes: knowing self, empirical, personal, and ethical.
      Substantiation of these was further enhanced from focus group data. Development
      of practical knowledge as a novice is influenced by the degree of engagement
      afforded to the graduate nurse and their skills of critical reflectivity. .

PMID- 19379118
TI  - Job stressors and social support behaviors: comparing intensive care units to
      wards in Jordan.
AB  - Studies about nurses' stressors and social support behaviors are limited. This
      study explored differences between Intensive Care Units (ICUs) and wards in
      regard to Jordanian nurses' job stressors and social support behaviors as well as
      predictors of the two concepts. A quantitative research design using a survey
      method was used. The Nursing Stress Scale (NSS) (Gray-Toft & Anderson 1981) and
      the Inventory of Social Supportive Behaviors (ISSB) (Barrera, Sandler & Ramsay
      1981) were used to collect data from a convenience sample of 228 nurses who were
      working in 12 ICUs and 235 nurses who were working in nine wards of 13 hospitals,
      with a total response rate of 66.2%. Stressors in ICUs were higher than those in
      wards. The ICUs scored higher than wards in 'conflict with physicians' subscale
      of NSS. The ICUs scored higher than wards in 'emotional support' and 'tangible
      assistance' subscales of ISSB. Shift worked, model of nursing care, and level of
      education predicted nurses' job stressors in ICUs and wards. 'Model of nursing
      care' was a shared predictor of social support behaviors in ICUs and wards. High
      job stressors and low social support behaviors were evidenced in Jordan. Job
      stressors were higher in ICUs than those in wards, thus more social support
      behaviors should be provided to nurses in ICUs. Nurses' stressors should be
      assessed and managed. In all settings in general and in ICUs in particular, nurse
      managers should use various social support behaviors to buffer the influence of
      job stressors on nurses.

PMID- 19379119
TI  - Prevalence, risk factors, consequences and strategies for reducing medication
      errors in Australian hospitals: a literature review.
AB  - The purpose of this paper is to examine medication errors in Australian hospitals
      from a nursing perspective. This paper provides a detailed review of past and
      current literature to examine prevalence rates and risk factors for medication
      errors. It also describes unintended injury or harm, also known as adverse
      events, associated with a medication error, and proposes strategies to counteract
      them. According to the literature, approximately two percent of patients in an
      acute hospital setting will experience a medication error. Administration of
      medications has remained a high risk task for registered nurses, and for this
      reason, the strategies to reduce error discussed in this paper will be
      predominantly nursing focussed. The occurrence of a medication error is a
      significant issue in the health care setting, and although the relative risk of
      an individual error occurring is low, the rate of error remains perceivably high
      in clinical practice today. With continual technological and pharmaceutical
      advances, the medication administration environment is becoming increasingly
      complex. Given the nature of medication therapy, it is near impossible to avoid
      all error, human and otherwise.

PMID- 19379120
TI  - Current situation of zalutumumab.
AB  - BACKGROUND: Increased EGFR expression has been observed in many tumours. This
      overexpression usually correlates with a more advanced disease stage, a poorer
      prognosis and a worse chemotherapy response. EGFR inhibition has been considered
      an attractive approach in cancer treatment. Various strategies to intervene in
      EGFR signalling have been developed, mainly receptor inhibition of extracellular
      domain using anti-EGFR monoclonal antibodies and receptor inhibition on the
      intracytoplasmic domain using small-molecule tyrosine kinase inhibitors.
      Cetuximab and panitumumab are the most developed anti-EGFR monoclonal antibodies,
      and there is plenty of published information about their current status
      Objective/methods: In this review we focus on Zalutumumab, an IgG1 completely
      human anti-EGFR monoclonal antibody. RESULTS/CONCLUSIONS: Apart from EGFR
      inhibition, another anti-neoplastic effect of zalutumumab has also been
      postulated, mediated by immune mechanisms, specifically by antibody-dependent
      cell cytotoxicity. Zalutumumab is under clinical development, mainly for squamous
      cell cancer of head and neck and there are also ongoing trials in NSCLC and
      colorectal cancer.

PMID- 19379121
TI  - Recombinant FSH in the treatment of oligozoospermia.
AB  - BACKGROUND: FSH plays a crucial role in human reproduction. Treatment with
      gonadotrophins has been shown to be effective in males affected by
      hypogonadotrophic hypogonadism. The success of this treatment has brought about
      the utilization of the same therapy in infertile oligozoospermic subjects, aimed
      at obtaining increased sperm count. This physiological role in spermatogenesis
      has induced various attempts to treat idiopathic oligozoospermic men with FSH,
      often inducing the restoration of normal spermatogenesis and spontaneous
      pregnancy. OBJECTIVE: To evaluate clinical efficacy of recombinant FSH in male
      infertility. METHODS: Evaluation of pharmacokinetic, pharmacodynamic properties,
      efficacy and safety of this hormone preparation, on the basis of the data
      published in literature. CONCLUSIONS: Recombinant FSH is effective, safe and well
      tolerated. Treatment with this hormone may represent a valid tool for infertile
      men. However it should be performed on selected patients utilizing some
      predictive parameters able to identify a priori responder subjects with high
      probability.

PMID- 19379122
TI  - Spinal cord injury and neural repair: focus on neuroregenerative approaches for
      spinal cord injury.
AB  - BACKGROUND: This review discusses the urgent need for improved therapeutic
      approaches aimed at restoring function following traumatic spinal cord injury
      (SCI). The focus of this paper is neuroregenerative approaches for SCI, with a
      highlighted comparison of recent advances in the field and comparisons to that
      made by Cethrin (Alseres Pharmaceuticals, Inc.), the leading nerve repair
      product. OBJECTIVE: This review first provides the reader with an understanding
      of SCI. The market for promising therapeutics that can either intervene in
      secondary etiological mechanisms or ameliorate symptoms associated with SCI are
      then discussed. The reader will also learn about Cethrin and its current status
      in clinical evaluation. METHODS: Review of the preclinical literature and
      clinical SCI trials relevant to the discovery and current development of Cethrin.
      RESULTS/CONCLUSION: In a recently concluded Phase I/IIa clinical trial involving
      37 patients with either cervical or thoracic SCIs, the evidence for Cethrin
      indicates that topical administration of either 0.3, 1, 3 or 6 mg of the
      recombinant rho inhibitor following surgical decompression is safe. Alseres has
      announced that planning is underway for a Phase IIB trial of Cethrin to include a
      placebo arm to assess better the drugs' clinical efficacy.

PMID- 19379123
TI  - The therapeutic potential of gamma-hydroxybutyric acid for alcohol dependence:
      balancing the risks and benefits. A focus on clinical data.
AB  - There is an increasing interest in studying the role of GABAergic medications in
      the treatment of alcohol dependence. The GABAergic drug gamma-hydroxybutyric acid
      (GHB) has been investigated in Europe as a possible treatment for alcohol
      dependence. In some European Countries, GHB has been approved as a treatment for
      alcohol dependence. However, this drug has also shown addictive properties,
      therefore raising questions about its safety in treating alcohol-dependent
      subjects. More recent research is focusing on the possibility of identifying
      alcohol-dependent subtypes without risk of developing GHB abuse. Finally, GHB and
      naltrexone combined together represent a possible approach deserving future
      investigations.

PMID- 19379124
TI  - Lixivaptan: a novel vasopressin receptor antagonist.
AB  - Arginine vasopressin, also known as antidiuretic hormone, is a neuropeptide that
      functions in the maintenance of body water homeostasis. Inappropriate secretion
      of vasopressin has been implicated in the pathophysiology of multiple diseases,
      including polycystic kidney disease, syndrome of inappropriate antidiuretic
      hormone (SIADH) secretion, and the hyponatremia commonly associated with
      cirrhosis and congestive heart failure. Vasopressin receptor antagonists are
      novel agents that block the physiologic actions of vasopressin. Lixivaptan is a
      vasopressin receptor antagonist with high V2 receptor affinity and is now
      undergoing Phase III clinical trials. Studies so far have demonstrated that
      lixivaptan is efficacious in the correction of hyponatremia in SIADH, heart
      failure and liver cirrhosis with ascites, and few adverse effects have been
      noted. Thus, lixivaptan remains a promising therapeutic modality for the
      treatment of multiple diseases and prevention of the associated morbidity and
      mortality associated with hyponatremia.

PMID- 19379126
TI  - Antisense oligonucleotide pharmacokinetics and metabolism.
AB  - BACKGROUND: The use of oligonucleotides as therapeutic agents has elicited a
      great deal of interest. Basic understanding and evaluation of the pharmacokinetic
      properties of oligonucleotides is foundational to their appropriate design and
      application. OBJECTIVE: To review the primary pharmacokinetic properties that
      drive successful use and delivery of oligonucleotides. METHODS: The primary data
      set available in the published literature for summarizing the pharmacokinetic
      properties of oligonucleotides exists for single strand phosphorothioate
      antisense oligonucleotides and their chimeric chemical modifications (second
      generation). Where possible, data from other classes of compounds are contrasted
      with this base class. RESULTS/CONCLUSION: Although there are several different
      classes of oligonucleotides being developed as therapeutic agents, their
      pharmacokinetic properties by class are primarily a function of their backbone
      chemistry and the resulting chemical relationship to biological stability and
      plasma protein binding properties.

PMID- 19379125
TI  - N-acetyltransferase SNPs: emerging concepts serve as a paradigm for understanding
      complexities of personalized medicine.
AB  - Arylamine N-acetyltransferase 1 and 2 exhibit single nucleotide polymorphisms in
      human populations that modify drug and carcinogen metabolism. This paper updates
      the identity, location and functional effects of these single nucleotide
      polymorphisms and then follows with emerging concepts for understanding why
      pharmacogenetic findings may not be replicated consistently. Using this paradigm
      as an example, laboratory-based mechanistic analyses can reveal complexities such
      that genetic polymorphisms become biologically and medically relevant when
      confounding factors are more fully understood and considered. As medical care
      moves to a more personalized approach, the implications of these confounding
      factors will be important in understanding the complexities of personalized
      medicine.

PMID- 19379127
TI  - The clinical pharmacology of eplerenone.
AB  - Eplerenone is an aldosterone receptor antagonist indicated for the treatment of
      hypertension and congestive heart failure. Eplerenone contains an epoxy group,
      which offers greater mineralocorticoid receptor specificity. It is an effective
      antihypertensive that has been shown to reduce morbidity and mortality in
      individuals with left ventricular dysfunction post myocardial infarction. Studies
      are continuing to determine whether the benefit of mineralocorticoid receptor
      blockade in advanced congestive heart failure is also observed when eplerenone
      treatment is initiated in earlier stages of the disease. The most common side
      effect is hyperkalemia necessitating close monitoring in individuals with
      diabetes and proteinuria, heart failure or in those who are taking moderate
      CYP450 3A4 inhibitors. It is category B in pregnancy.

PMID- 19379128
TI  - Clinical role of diosmectite in the management of diarrhea.
AB  - BACKGROUND: Diosmectite (DS), an antidiarrheal absorbent natural clay, was
      proposed for treatment of acute gastroenteritis and more recently considered for
      diarrhea within the functional bowel disorder syndrome. OBJECTIVE: To review
      pharmacology efficacy, mechanisms of action and safety of DS. METHODS: We
      consulted PubMed/Medline using the keywords of smectite and diarrhea or
      gastroenteritis, and reviewed most recent recommendations by scientific
      societies. CONCLUSIONS: Solid data show that DS is effective in infectious
      diarrhea, mainly as an ion antisecretory agent and in preventing intestinal
      damage. Despite clinical data being consistent and convincing, DS is not
      considered as first-line treatment because of the presence of alternative
      therapeutic options. However, it definitely may play a role in infectious
      colitis, where treatment options are less convincing. Some available evidences
      demonstrate a role of DS in functional diarrhea.

PMID- 19379129
TI  - Identification of a pancreatic stellate cell population with properties of
      progenitor cells: new role for stellate cells in the pancreas.
AB  - Numerous studies conducted in a diversity of adult tissues have shown that
      certain stem cells are characterized by the expression of a protein known as the
      ABCG2 transporter (where ABC is ATP- binding cassette). In the adult pancreas,
      although various multipotent progenitors have been proposed, the ABCG2 marker has
      only been detected in the so-called 'side population' (a primitive haematopoietic
      cell population with a multipotential capacity). In the present study we sought
      to identify new ABCG2+ pancreatic cell populations and to explore whether they
      exhibit the properties of progenitor cells. We isolated and expanded mitoxantrone
      resistant cells from pancreata of lactating rats by drug selection. These cells
      were characterized and maintained in different stages of differentiation using
      several media 'cocktails' plus Matrigel (BD Biosciences). Differentiation was
      assessed by RT-PCR (reverse transcription-PCR), immunocytochemistry, electron
      microscopy and ELISA. The expanded cell population demonstrated a phenotype of
      PaSCs (pancreatic stellate cells). Spontaneous cell clusters occurred during cell
      expansion and they showed weak expression of the transcription factor Pdx1
      (pancreatic and duodenal homeobox 1). Moreover, the presence of inductive factors
      in the Matrigel plus exendin-4 led to an increase in Pdx1 and endocrine genes,
      such as insulin, islet amyloid polypeptide, glucagon, the glucose transporter
      GLUT2, chromogranin A and the convertases PC1/3 and PC2 were also detected.
      Immunocytochemical analysis showed co-localization of insulin and C-peptide,
      whereas ultrastructural studies revealed the presence of granules. Insulin
      secretion from cell clusters was detected in the cell culture medium. We
      identified a population of PaSCs that express the ABCG2+ transporter and have the
      capacity to transdifferentiate into insulin-producing cells. Although the
      potential therapeutic application remains to be tested, PaSCs could represent a
      future option for insulin replacement in diabetes research.

PMID- 19379132
TI  - Towards an integration of ecological stoichiometry and the metabolic theory of
      ecology to better understand nutrient cycling.
AB  - Ecologists have long recognized that species are sustained by the flux, storage
      and turnover of two biological currencies: energy, which fuels biological
      metabolism and materials (i.e. chemical elements), which are used to construct
      biomass. Ecological theories often describe the dynamics of populations,
      communities and ecosystems in terms of either energy (e.g. population-dynamics
      theory) or materials (e.g. resource-competition theory). These two classes of
      theory have been formulated using different assumptions, and yield distinct, but
      often complementary predictions for the same or similar phenomena. For example,
      the energy-based equation of von Bertalanffy and the nutrient-based equation of
      Droop both describe growth. Yet, there is relatively little theoretical
      understanding of how these two distinct classes of theory, and the currencies
      they use, are interrelated. Here, we begin to address this issue by integrating
      models and concepts from two rapidly developing theories, the metabolic theory of
      ecology and ecological stoichiometry theory. We show how combining these
      theories, using recently published theory and data along with new theoretical
      formulations, leads to novel predictions on the flux, storage and turnover of
      energy and materials that apply to animals, plants and unicells. The theory and
      results presented here highlight the potential for developing a more general
      ecological theory that explicitly relates the energetics and stoichiometry of
      individuals, communities and ecosystems to subcellular structures and processes.
      We conclude by discussing the basic and applied implications of such a theory,
      and the prospects and challenges for further development.

PMID- 19379130
TI  - Inhibition of myeloperoxidase-mediated hypochlorous acid production by
      nitroxides.
AB  - Tissue damage resulting from the extracellular production of HOCl (hypochlorous
      acid) by the MPO (myeloperoxidase)-hydrogen peroxide-chloride system of activated
      phagocytes is implicated as a key event in the progression of a number of human
      inflammatory diseases. Consequently, there is considerable interest in the
      development of therapeutically useful MPO inhibitors. Nitroxides are well
      established antioxidant compounds of low toxicity that can attenuate oxidative
      damage in animal models of inflammatory disease. They are believed to exert
      protective effects principally by acting as superoxide dismutase mimetics or
      radical scavengers. However, we show here that nitroxides can also potently
      inhibit MPO-mediated HOCl production, with the nitroxide 4-aminoTEMPO inhibiting
      HOCl production by MPO and by neutrophils with IC50 values of approx. 1 and 6
      microM respectively. Structure-activity relationships were determined for a range
      of aliphatic and aromatic nitroxides, and inhibition of oxidative damage to two
      biologically-important protein targets (albumin and perlecan) are demonstrated.
      Inhibition was shown to involve one-electron oxidation of the nitroxides by the
      compound I form of MPO and accumulation of compound II. Haem destruction was also
      observed with some nitroxides. Inhibition of neutrophil HOCl production by
      nitroxides was antagonized by neutrophil-derived superoxide, with this attributed
      to superoxide-mediated reduction of compound II. This effect was marginal with 4
      aminoTEMPO, probably due to the efficient superoxide dismutase-mimetic activity
      of this nitroxide. Overall, these data indicate that nitroxides have considerable
      promise as therapeutic agents for the inhibition of MPO-mediated damage in
      inflammatory diseases.

PMID- 19379133
TI  - Resilience of tropical rain forests: tree community reassembly in secondary
      forests.
AB  - Understanding the recovery dynamics of ecosystems presents a major challenge in
      the human-impacted tropics. We tested whether secondary forests follow
      equilibrium or non-equilibrium dynamics by evaluating community reassembly over
      time, across different successional stages, and among multiple life stages. Based
      on long-term and static data from six 1-ha plots in NE Costa Rica, we show that
      secondary forests are undergoing reassembly of canopy tree and palm species
      composition through the successful recruitment of seedlings, saplings, and young
      trees of mature forest species. Such patterns were observed over time within
      sites and across successional stages. Floristic reassembly in secondary forests
      showed a clear convergence with mature forest community composition, supporting
      an equilibrium model. This resilience stems from three key factors co-occurring
      locally: high abundance of generalist species in the regional flora, high levels
      of seed dispersal, and local presence of old-growth forest remnants.

PMID- 19379134
TI  - A novel method for identifying behavioural changes in animal movement data.
AB  - A goal of animal movement analysis is to reveal behavioural mechanisms by which
      organisms utilize complex and variable environments. Statistical analysis of
      movement data is complicated by the fact that the data are multidimensional,
      autocorrelated and often marked by error and irregular measurement intervals or
      gappiness. Furthermore, movement data reflect behaviours that are themselves
      heterogeneous. Here, we model movement data as a subsampling of a continuous
      stochastic processes, and introduce the behavioural change point analysis (BCPA),
      a likelihood-based method that allows for the identification of significant
      structural changes. The BCPA is robust to gappiness and measurement error,
      computationally efficient, easy to implement and reveals structure that is
      otherwise difficult to discern. We apply the analysis to a GPS movement track of
      a northern fur seal (Callorhinus ursinus), revealing an unexpectedly complex
      diurnal behavioural profile, and demonstrate its robustness to the greater errors
      associated with the ARGOS tracking system. By informing empirical interpretation
      of movement data, we suggest that the BCPA can eventually motivate the
      development of mechanistic behavioural models.

PMID- 19379135
TI  - Plant-pollinator networks: adding the pollinator's perspective.
AB  - Pollination network studies are based on pollinator surveys conducted on focal
      plants. This plant-centred approach provides insufficient information on flower
      visitation habits of rare pollinator species, which are the majority in
      pollinator communities. As a result, pollination networks contain very high
      proportions of pollinator species linked to a single plant species (extreme
      specialists), a pattern that contrasts with the widely accepted view that plant
      pollinator interactions are mostly generalized. In this study of a Mediterranean
      scrubland community in NE Spain we supplement data from an intensive field survey
      with the analysis of pollen loads carried by pollinators. We observed 4265
      contacts corresponding to 19 plant and 122 pollinator species. The addition of
      pollen data unveiled a very significant number of interactions, resulting in
      important network structural changes. Connectance increased 1.43-fold, mean plant
      connectivity went from 18.5 to 26.4, and mean pollinator connectivity from 2.9 to
      4.1. Extreme specialist pollinator species decreased 0.6-fold, suggesting that
      ecological specialization is often overestimated in plant-pollinator networks. We
      expected a greater connectivity increase in rare species, and consequently a
      decrease in the level of asymmetric specialization. However, new links
      preferentially attached to already highly connected nodes and, as a result, both
      nestedness and centralization increased. The addition of pollen data revealed the
      existence of four clearly defined modules that were not apparent when only field
      survey data were used. Three of these modules had a strong phenological
      component. In comparison to other pollination webs, our network had a high
      proportion of connector links and species. That is, although significant, the
      four modules were far from isolated.

PMID- 19379136
TI  - Projected impacts of climate change on a continent-wide protected area network.
AB  - Despite widespread concern, the continuing effectiveness of networks of protected
      areas under projected 21st century climate change is uncertain. Shifts in
      species' distributions could mean these resources will cease to afford protection
      to those species for which they were originally established. Using modelled
      projected shifts in the distributions of sub-Saharan Africa's entire breeding
      avifauna, we show that species turnover across the continent's Important Bird
      Area (IBA) network is likely to vary regionally and will be substantial at many
      sites (> 50% at 42% of IBAs by 2085 for priority species). Persistence of
      suitable climate space across the network as a whole, however, is notably high,
      with 88-92% of priority species retaining suitable climate space in >or= 1 IBA(s)
      in which they are currently found. Only 7-8 priority species lose climatic
      representation from the network. Hence, despite the likelihood of significant
      community disruption, we demonstrate that rigorously defined networks of
      protected areas can play a key role in mitigating the worst impacts of climate
      change on biodiversity.

PMID- 19379137
TI  - Biodiversity maintenance mechanisms differ between native and novel exotic
      dominated communities.
AB  - In many systems, native communities are being replaced by novel exotic-dominated
      ones. We experimentally compared species diversity decline between nine-species
      grassland communities under field conditions to test whether diversity
      maintenance mechanisms differed between communities containing all exotic or all
      native species using a pool of 40 species. Aboveground biomass was greater in
      exotic than native plots, and this difference was larger in mixtures than in
      monocultures. Species diversity declined more in exotic than native communities
      and declines were explained by different mechanisms. In exotic communities,
      overyielding species had high biomass in monoculture and diversity declined
      linearly as this selection effect increased. In native communities, however,
      overyielding species had low biomass in monoculture and there was no relationship
      between the selection effect and diversity decline. This suggests that, for this
      system, yielding behaviour is fundamentally different between presumably co
      evolved natives and coevolutionarily naive exotic species, and that native-exotic
      status is important to consider.

PMID- 19379138
TI  - Biodiversity, productivity and the temporal stability of productivity: patterns
      and processes.
AB  - Theory predicts that the temporal stability of productivity, measured as the
      ratio of the mean to the standard deviation of community biomass, increases with
      species richness and evenness. We used experimental species mixtures of grassland
      plants to test this hypothesis and identified the mechanisms involved.
      Additionally, we tested whether biodiversity, productivity and temporal stability
      were similarly influenced by particular types of species interactions. We found
      that productivity was less variable among years in plots planted with more
      species. Temporal stability did not depend on whether the species were planted
      equally abundant (high evenness) or not (realistically low evenness). Greater
      richness increased temporal stability by increasing overyielding, asynchrony of
      species fluctuations and statistical averaging. Species interactions that
      favoured unproductive species increased both biodiversity and temporal stability.
      Species interactions that resulted in niche partitioning or facilitation
      increased both productivity and temporal stability. Thus, species interactions
      can promote biodiversity and ecosystem services.

PMID- 19379139
TI  - A slow life in hell or a fast life in heaven: demographic analyses of contrasting
      roe deer populations.
AB  - 1. Environmental conditions shape population growth through their impact on
      demographic parameters. While knowledge has accumulated concerning the effects of
      population density and climatic conditions, a topical question now concerns how
      predation and harvest influence demographic parameters and population growth
      (lambda). 2. We performed a comparative demographic analysis based on projection
      matrix models for female roe deer. Population-specific matrices were
      parameterized based on longitudinal data from five intensively monitored
      populations in Norway and France, spanning a large variability in environmental
      characteristics such as densities of large predators, hunter harvest and
      seasonality. 3. As expected for a large iteroparous vertebrate, temporal
      variation was invariably higher in recruitment than in adult survival, and the
      elasticity of adult survival was consistently higher than that of recruitment.
      However, the relative difference in elasticity of lambda to recruitment and adult
      survival varied strongly across populations, and was closely correlated with
      adult survival. 4. Different traits accounted for most of the variance in lambda
      in different ecological settings. Adult survival generally contributed more in
      populations with low mean adult survival and low mean growth rate during the
      study period. Hunters and predators (Eurasian lynx and red foxes) occurred in two
      of our study populations and contributed substantially to the variance in lambda,
      accounting for a total of 35% and 70% in the two populations respectively. 5.
      Across populations, we did not find any evidence that roe deer increased their
      reproductive output when faced with harsh conditions, resulting in some
      populations having negative growth rates. 6. Generation time, a measure of the
      speed of the life-history cycle, increased from less than 4 years in the most
      productive population ('roe deer heaven') to more than 6 years in declining
      populations facing predation from lynx, red fox and hunters ('roe deer hell'),
      and was tightly and inversely correlated with lambda. Such a deceleration of the
      life cycle in declining populations might be a general feature in large
      herbivores. 7. Our results shows that the plethora of environmental conditions
      faced by populations of large herbivores also induce high intraspecific variation
      in their ranking along the 'fast-slow' continuum of life-history tactics.

PMID- 19379140
TI  - Maturation trends in red deer females over 39 years in harvested populations.
AB  - 1. There is increasing awareness that heavy harvesting can lead to rapid
      evolution towards earlier sexual maturation. With increased harvest pressure,
      individuals that begin reproduction at light weights have a greater chance of
      reproducing at least once compared with individuals that begin reproduction at
      heavier weights and hence later in life. Although well documented in fish, this
      has not been empirically tested for harvested populations of mammals in
      terrestrial ecosystems differing in many environmental aspects. 2. Using data
      from 3856 female red deer (Cervus elaphus L.) from three harvested populations,
      we tested whether red deer maturity changed from 1967 to 2006. In these
      populations, density has increased markedly over the time period reducing body
      mass of deer, which has decreased the proportion of females maturing as
      yearlings. We therefore assessed trends in maturation as yearlings after
      controlling for body mass. Long-lived iteroparous ungulate females are expected
      to have a prudent life history not risking their future survival and reproduction
      under harsh conditions (e.g. at high density). An alternative to the harvest
      induced evolution hypothesis is that maturation is driven mainly by phenotypic
      responses to increased density, and we predicted later maturation even after
      controlling for the reduction in body mass. 3. There was a marked trend towards
      later age at maturation in one out of three populations (after controlling for
      the effect of reduced body mass due to increased density), while there was no
      marked trend in the two other populations. The harvesting-induced evolution
      hypothesis was therefore not supported. However, although the decline was
      predicted from the prudent life-history tactic hypothesis, the estimate for the
      density effect was positive rather than negative after accounting for the year
      trend. Although we did not find support for the harvest-induced earlier
      maturation hypothesis, evidence was not clearly in favour of the alternative
      hypothesis. 4. Our study contrasts results from trophy-hunting traditions
      targeting large males, and points to a potential role of the cultural tradition.
      Harvesting in Scandinavia mainly aims for meat targeting calves and yearlings
      (and males), which is less likely to yield an evolutionary response in maturation
      of females. Our results, although being on a plastic trait and not directly on
      genetic make-up, are indicative that harvesting-induced evolution is weak on age
      at maturation in these populations under the current management regime.

PMID- 19379143
TI  - Polymorphisms in p53 and the p53 pathway: roles in cancer susceptibility and
      response to treatment.
AB  - The p53 tumour suppressor protein lies at the crossroads of multiple cellular
      response pathways that control the fate of the cell in response to endogenous or
      exogenous stresses and inactivation of the p53 tumour suppressor signalling
      pathway is seen in most human cancers. Such aberrant p53 activity may be caused
      by mutations in the TP53 gene sequence producing truncated or inactive mutant
      proteins, or by aberrant production of other proteins that regulate p53 activity,
      such as gene amplification and overexpression of MDM2 or viral proteins that
      inhibit or degrade p53. Recent studies have also suggested that inherited genetic
      polymorphisms in the p53 pathway influence tumour formation, progression and/or
      response to therapy. In some cases, these variants are clearly associated with
      clinico-pathological variables or prognosis of cancer, whereas in other cases the
      evidence is less conclusive. Here, we review the evidence that common
      polymorphisms in various aspects of p53 biology have important consequences for
      overall tumour susceptibility, clinico-pathology and prognosis. We also suggest
      reasons for some of the reported discrepancies in the effects of common
      polymorphisms on tumourigenesis, which relate to the complexity of effects on
      tumour formation in combination with other oncogenic changes and other
      polymorphisms. It is likely that future studies of combinations of polymorphisms
      in the p53 pathway will be useful for predicting tumour susceptibility in the
      human population and may serve as predictive biomarkers of tumour response to
      standard therapies.

PMID- 19379142
TI  - Drug releasing systems in cardiovascular tissue engineering.
AB  - Heart disease and atherosclerosis are the leading causes of morbidity and
      mortality worldwide. The lack of suitable autologous grafts has produced a need
      for artificial grafts; however, current artificial grafts carry significant
      limitations, including thrombosis, infection, limited durability and the
      inability to grow. Tissue engineering of blood vessels, cardiovascular structures
      and whole organs is a promising approach for creating replacement tissues to
      repair congenital defects and/or diseased tissues. In an attempt to surmount the
      shortcomings of artificial grafts, tissue-engineered cardiovascular graft
      (TECVG), constructs obtained using cultured autologous vascular cells seeded onto
      a synthetic biodegradable polymer scaffold, have been developed. Autologous
      TECVGs have the potential advantages of growth, durability, resistance to
      infection, and freedom from problems of rejection, thrombogenicity and donor
      scarcity. Moreover polymers engrafted with growth factors, cytokines, drugs have
      been developed allowing drug-releasing systems capable of focused and localized
      delivery of molecules depending on the environmental requirements and the milieu
      in which the scaffold is placed. A broad range of applications for compound
      releasing, tissue-engineered grafts have been suggested ranging from drug
      delivery to gene therapy. This review will describe advances in the development
      of drug-delivery systems for cardiovascular applications focusing on the
      manufacturing techniques and on the compounds delivered by these systems to date.

PMID- 19379144
TI  - Circulating endothelial cells, microparticles and progenitors: key players
      towards the definition of vascular competence.
AB  - The balance between lesion and regeneration of the endothelium is critical for
      the maintenance of vessel integrity. Exposure to cardiovascular risk factors
      (CRF) alters the regulatory functions of the endothelium that progresses from a
      quiescent state to activation, apoptosis and death. In the last 10 years,
      identification of circulating endothelial cells (CEC) and endothelial-derived
      microparticles (EMP) in the circulation has raised considerable interest as non
      invasive markers of vascular dysfunction. Indeed, these endothelial-derived
      biomarkers were associated with most of the CRFs, were indicative of a poor
      clinical outcome in atherothrombotic disorders and correlated with established
      parameters of endothelial dysfunction. CEC and EMP also behave as potential
      pathogenic vectors able to accelerate endothelial dysfunction and promote disease
      progression. The endothelial response to injury has been enlarged by the
      discovery of a powerful physiological repair process based on the recruitment of
      circulating endothelial progenitor cells (EPC) from the bone marrow. Recent
      studies indicate that reduction of EPC number and function by CRF plays a
      critical role in the progression of cardiovascular diseases. This EPC-mediated
      repair to injury response can be integrated into a clinical endothelial phenotype
      defining the 'vascular competence' of each individual. In the future, provided
      that standardization of available methodologies could be achieved, multimarker
      strategies combining CEC, EMP and EPC levels as integrative markers of 'vascular
      competence' may offer new perspectives to assess vascular risk and to monitor
      treatment efficacy.

PMID- 19379146
TI  - Target for glycemic control in type 2 diabetic patients on hemodialysis: effects
      of anemia and erythropoietin injection on hemoglobin A(1c).
AB  - In hemodialysis (HD) patients the glycated hemoglobin (Hb(A1c)) level may
      underestimate glycemic control. The aim of this study is to estimate accurate
      glycemic control in type 2 diabetic patients on HD. Type 2 diabetes patients (N =
      87) who had been receiving maintenance HD for at least one year were enrolled.
      Hb(A1c) and the percentage of glycated albumin relative to total the serum
      albumin (%GA) were measured in blood samples and the factors that affected the
      %GA/Hb(A1c) ratio were examined. There were significant and positive correlations
      between the plasma glucose and either the Hb(A1c) levels (r = 0.539, P < 0.01) or
      the %GA level (r = 0.520, P < 0.01). No relationship between the serum albumin
      levels and %GA levels was observed. A weekly dose of erythropoietin (EPO) was
      positively correlated with the ratio of %GA/Hb(A1c) and hematocrit (Ht)
      correlated negatively. There was no significant correlation between the
      %GA/Hb(A1c) level and the EPO dose in patients with Ht > or = 30%, although a
      significant correlation was found between those parameters in the Ht < 30% group.
      The mean of the %GA/Hb(A1c) ratios in patients with Ht > or = 30%, with Ht < 30%
      and treated with EPO < 100 IU/kg/week, and with Ht < 30% and treated with EPO >
      or = 100 IU/kg/week were 3.41, 3.56 and 4.13, respectively. In HD patients,
      accurate glycemic control may be estimated as: Hb(A1c) x 1.14 if Ht > or = 30%;
      Hb(A1c) x 1.19 if Ht < 30% and treated with low dosages of EPO; and Hb(A1c) x
      1.38 if Ht < 30% and treated with high dosages of EPO.

PMID- 19379147
TI  - Hypoglycemia in diabetic patients undergoing chronic hemodialysis.
AB  - The aim of our study was to determine if different hypoglycemic therapies are
      associated with more frequent episodes of hypoglycemia in diabetes patients
      undergoing long-term hemodialysis. We conducted a prospective cohort study that
      included 102 diabetes patients who were undergoing long-term hemodialysis. The
      frequency of symptomatic hypoglycemic episodes, intradialytic hypotension,
      antihypertension medication, hypoglycemic therapy regimens, dialysate contents,
      and laboratory data were reviewed. The duration of follow-up was three months.
      Fifty-four (52.9%) patients were categorized as hypoglycemic and 48 (47.1%)
      patients as non-hypoglycemic. The serum albumin levels of the hypoglycemic and
      non-hypoglycemic patients were 3.18 +/- 0.34 g/dL and 3.44 +/- 0.33 g/dL
      respectively (P < 0.001). The prevalence of intradialytic hypotension is
      significantly higher in the hypoglycemic patients (44.4%) than in the non
      hypoglycemic patients (20.8%) (P = 0.012). The risk of hypoglycemia differed
      significantly between the patients taking oral hypoglycemic agents (OHAs) and
      those receiving purely insulin therapy (P = 0.035). Multivariate analysis
      revealed that the serum albumin (odds ratio [OR] 0.093, 95% confidence interval
      [CI] 0.021-0.409), intradialytic hypotension (OR 2.755, 95% CI 1.048-7.228), and
      OHA therapy (OR 0.337, 95% CI 0.128-0.888) were independent factors of
      hypoglycemia. The patients treated only with meglitinides as hypoglycemic therapy
      had a significantly lower risk of hypoglycemia than those receiving mixed insulin
      therapy (P = 0.016). Frequent episodes of intradialytic hypotension and
      hypoalbuminemia are powerful clinical predictors of hypoglycemia in diabetes
      patients undergoing hemodialysis. It was also found that OHAs do not pose a
      higher risk of hypoglycemia than insulin in diabetic patients undergoing
      hemodialysis.

PMID- 19379148
TI  - Risk factors of normal ankle-brachial index and low toe-brachial index in
      hemodialysis patients.
AB  - The prevalence of peripheral arterial occlusive disease is high in patients with
      terminal renal failure, and it is a major problem in those on dialysis. A low
      ankle-brachial index (ABI) suggests the presence of arterial stenotic lesions
      between the aorta and the ankle joint, while a low toe-brachial index (TBI)
      suggests stenotic lesions between the aorta and the toes. Therefore, a normal ABI
      (> or =0.9) and a low TBI (<0.6) may indicate the presence of stenotic lesions
      located only on the peripheral side of the ankle joint. In the present study,
      risk factors of normal ABI/low TBI were investigated. In 115 patients on
      maintenance dialysis, the ABI and TBI were simultaneously measured, and the
      background factors and laboratory data of patients with normal ABI/low TBI (L
      group) and those with normal ABI/normal TBI (> or =0.6) (N group) were compared.
      Low ankle-brachial and toe-brachial indices were detected in 13% and 22% of the
      patients, respectively. Comparison of the background factors and laboratory data
      between the N and L groups showed that the ratio of diabetes mellitus,
      interdialytic body weight gain, and Hb(A1c) values were significantly higher in
      the L group than in the N group. It was clarified that diabetes and excess body
      weight gain are involved as risk factors in dialysis patients with normal ABI/low
      TBI.

PMID- 19379145
TI  - Slow and steady is the key to beta-cell replication.
AB  - The beta-cells of the pancreas are responsible for insulin production and their
      destruction results in type I diabetes. beta-cell maintenance, growth and
      regenerative repair is thought to occur predominately, if not exclusively,
      through the replication of existing beta-cells, not via an adult stem cell. It
      was recently found that all beta-cells contribute equally to islet growth and
      maintenance. The fact that all beta-cells replicate homogeneously makes it
      possible to set up straightforward screens for factors that increase beta-cell
      replication either In vitro or in vivo. It is possible that a circulating factor
      may be capable of increasing beta-cell replication or that intrinsic cell cycle
      regulators may affect beta-cell growth. An improved understanding of the in vivo
      maintenance and growth of beta-cells will facilitate efforts to expand beta-cells
      In vitro and may lead to new treatments for diabetes.

PMID- 19379149
TI  - Plasmapheresis and intravenous immunoglobulin in early antibody-mediated
      rejection of the renal allograft: a single-center experience.
AB  - Antibody-mediated rejection (AMR) is a rare complication which often results in
      the loss of the kidney graft. The objective of this retrospective single center
      study was to evaluate two different approaches to AMR. We retrospectively
      evaluated data files from 936 patients who had undergone renal transplantation in
      2002-2006. In 2002-2003, patients with AMR were treated with five plasmapheresis
      sessions (PP group, N = 13), and in 2004-2006 they received five plasmapheresis
      session along with intravenous immunoglobulin 0.5 g/kg (PP+IVIg group, N = 11).
      Twelve months of follow-up data was analyzed. First year graft survival was
      significantly higher in the PP+IVIg group than in the PP group (90.9% vs. 46.2%;
      P = 0.044); similarly, patient survival was higher in the PP+IVIg group (100% vs.
      76.9%; P = 0.056). The incidence of infectious complications was similar in both
      groups. In re-biopsies, patients in the PP group often suffered from cellular
      rejection. The deposition of C4d complement was similar in re-biopsies in both
      groups. In this large single center study we proved the superiority of
      plasmapheresis with intravenous immunoglobulin administration in the treatment of
      early AMR of renal allografts.

PMID- 19379150
TI  - Malnutrition-inflammation complex syndrome and hepatitis C in maintenance
      hemodialysis patients.
AB  - Protein-energy malnutrition and inflammation are among the leading causes of poor
      outcome in hemodialysis patients. Hepatitis C virus (HCV) infection is
      accompanied by elevated proinflammatory mediators, also found in dialysis
      patients with malnutrition-inflammation complex syndrome. We aimed to study the
      rate and characteristics of malnutrition-inflammation complex syndrome (MICS) in
      hemodialysis patients, especially those with hepatitis C. The study included 147
      patients (mean age 55.1 +/- 12.9 years), 24.5% of whom were HCV-positive,
      undergoing adequate hemodialysis three times a week for the last 52.7 +/- 52.5
      months. Parameters of nutrition and inflammation were investigated to evaluate
      MICS. HCV-positive vs. HCV-negative patients had significantly higher hematocrit
      (29.6 +/- 4.5 g/dL vs. 28.1 +/- 4.3, P < 0.05), uric acid (345.8 +/- 96.5 vs.
      321.3 +/- 118.8 micromol/mL, P < 0.05), aspartate aminotransferase (AST, also
      known as serum glutamic oxaloacetic transaminase [SGOT]) (23.3 +/- 14.9 vs. 17.8
      +/- 9 U/L, P < 0.008), alanine aminotransferase (ALT, also known as serum
      glutamic pyruvic transaminase [SGPT]) (41.2 +/- 28.7 vs. 26.6 +/- 17.1 U/L, P <
      0.0003), serum creatinine (980.4 +/- 219.1 vs. 888.4 +/- 202.9 micromol/mL, P <
      0.022), intact parathyroid hormone (329.7 +/- 630.5 vs. 110.2 +/- 145.3 pg/mL, P
      < 0.002), malnutrition-inflammation score (7.4 +/- 5.2 vs. 5.6 +/- 4.1, P <
      0.038), and Charlson comorbidity index (4.5 +/- 1.5 vs. 4 +/- 1.4, P < 0.05).
      MICS had a prevalence of 20-40% in our study. HCV-positive patients had a
      significantly higher prevalence of MICS than HCV-negative patients (30-40% vs. 20
      30%).

PMID- 19379151
TI  - Low density lipoprotein apheresis in pediatric patients with homozygous familial
      hypercholesterolemia.
AB  - The aim of the present study is to clarify the low density lipoprotein apheresis
      procedure for pediatric patients with homozygous familial hypercholesterolemia
      (FH) in terms of efficacy, adverse effects and difficulties. The follow-up was
      carried out using an open, prospective uncontrolled clinical design. Data were
      collected from 10 patients (with an average age of 8.4 +/- 4.7 years) with FH
      treated with double filtration plasmapheresis. The total time span of follow-up
      covered five years (30.2 +/- 17.8 months [range 9-60 months]) and more than 600
      sessions (62.1 +/- 35.5 sessions per patient [range 18-120 sessions]) were
      evaluated. The mean low density lipoprotein cholesterol (LDL-C) pre-treatment
      value was 375.5 +/- 127.5 mg/dL, and the post-treatment value was 147.5 +/- 73.9
      mg/dL. This corresponded to a 62.8 +/- 10.3% (43-73%) acute reduction of LDL-C,
      while the mean high density lipoprotein cholesterol losses amounted to 41%. The
      chronic reduction in LDL-C ranged from 18 to 52%, with a mean level of 36.4 +/-
      11.7%. The most frequently occurring technical problems were related to blood
      lines: puncture difficulties (4.5%), insufficient blood flow (3.5%), and
      obturation of the blood lines (2.4%). The main clinical adverse effects were
      hypotension (0.2%), chills/feeling cold (0.1%), and nausea and vomiting (0.2%).
      We observed that the low pediatric patient tolerance is the main problem in
      compliance with treatment. In conclusion, LDL apheresis, started under the age of
      eight years, combined with lipid-lowering drugs, provides a safe and effective
      lowering of the mean LDL-C levels in pediatric homozygous FH; and there are more
      problems with compliance for pediatric LDL apheresis than in the adult
      population.

PMID- 19379152
TI  - Single lipoprotein apheresis session improves cardiac microvascular function in
      patients with elevated lipoprotein(a): detection by stress/rest perfusion
      magnetic resonance imaging.
AB  - The aim of this study was to explore the effects of a single lipoprotein
      apheresis session on myocardial stress/rest (S/R) perfusion in patients with
      elevated lipoprotein(a) (Lp(a)) and coronary artery disease using cardiac
      magnetic resonance imaging. Twenty patients with Lp(a) > 60 mg/dL and coronary
      artery disease were randomized into a control or a treatment group. Both groups
      underwent cardiac magnetic resonance imaging with assessment of left ventricular
      function, perfusion and viability, and the treatment group underwent lipoprotein
      apheresis immediately afterwards. Repeat magnetic resonance imaging was performed
      at 24 h for both groups and at 96 h for just the treatment group. The
      transmyocardial perfusion gradient (i.e. endo-epi ratio [EER]) was determined and
      a comprehensive parameter of resting and adenosine-induced stress perfusion was
      derived (EER-S/R). While the hematocrit remained unchanged, apheresis reduced
      lipoproteins and rheological parameters: Lp(a) - 55.1%, total cholesterol -
      34.5%, low density lipoprotein (LDL) - 54.6%, Lp(a)-corrected LDL - 54.3%, high
      density lipoprotein - 17.4%, apolipoprotein B - 39.2%, plasma viscosity - 10.7%,
      and fibrinogen - 30.6% at 24 h (P < 0.05 for all). At 96 h these parameters,
      except for plasma viscosity, apolipoprotein B and Lp(a)-corrected LDL, recovered
      but did not reach baseline values (P < 0.05 for all). The EER-S/R at 24 h was
      lowered by therapy (DeltaEER-S/R 5%; P < 0.03), whereas this effect disappeared
      at 96 h. The ejection fraction (EF) was slightly improved at 24 h (67.07 +/-
      6.28% vs. 64.89 +/- 6.39%; DeltaEF 2.2%, P < 0.05) and returned to baseline at 96
      h. In the control group no corresponding changes were detected. In conclusion,
      cardiac magnetic resonance imaging detects subtle treatment-related changes in
      regional myocardial perfusion in patients with elevated Lp(a) and coronary artery
      disease undergoing lipoprotein apheresis.

PMID- 19379153
TI  - Granulocyte and monocyte adsorption apheresis therapy modulates monocyte-derived
      dendritic cell function in patients with ulcerative colitis.
AB  - The aim of this study was to elucidate the molecular mechanisms responsible for
      the therapeutic effects of granulocyte and monocyte adsorption apheresis (GMA).
      We investigated the alterations in circulating monocyte subsets and monocyte
      derived dendritic cell (moDC) function after GMA therapy in ulcerative colitis
      (UC) patients. Eighteen patients with UC were enrolled: 14 patients were
      responders, and 4 patients were non-responders. Peripheral venous blood was
      obtained within 5 min before and 5 min after GMA therapy. Flow cytometric
      analysis for monocyte markers (CD14/CD16) was then performed. Monocyte-derived
      dendritic cells were obtained and alterations in their phenotype were analyzed by
      flow cytometry. Their function was also analyzed in a mixed lymphocyte reaction
      assay between allo-naive T lymphocytes. Flow cytometric analysis for
      intracellular interferon (IFN)-gamma (T-helper 1 cells) and interleukin (IL)-4 (T
      helper 2 cells) was then performed for the stimulated T lymphocytes. In patients
      who responded to GMA, the average numbers of monocytes, especially CD16(+)
      monocytes, were significantly decreased after therapy (P < 0.05). In responders,
      post-GMA moDCs expressed significantly lower CD80 and B7-DC, which are one of the
      stimulation and maturation markers of dendritic cells, compared to pre-GMA moDCs.
      CD83, CD86 and human leukocyte antigen-DR also showed a tendency to decrease. In
      responders, naive T lymphocytes stimulated with post-GMA moDCs produced
      significantly less IFN-gamma and IL-4 compared to those stimulated with pre-GMA
      moDCs. The results of our study show that some of the immunosuppressive effects
      of GMA therapy may be associated with the modulation of monocyte subsets and moDC
      function.

PMID- 19379154
TI  - A case report of amitriptyline poisoning successfully treated with the
      application of plasma exchange.
AB  - Amitriptyline is a very frequently prescribed antidepressant agent and is very
      often involved in attempted suicides. Amitriptyline intoxication necessitates
      primary therapeutic approaches that include gastric irrigation and recurrent
      administration of activated charcoal. In the case of pronounced anticholinergic
      findings, physostigmine is of proven benefit and hypertonic sodium bicarbonate
      can be used to shorten the QRS duration and AV interval. In cases of a comatosed
      state, hemoperfusion and plasma exchange can be used. In this case report we
      present a case of severe amitriptyline poisoning that we successfully managed
      with plasma exchange. We confirmed a 59.5% reduction in the amitriptyline plasma
      level in our patient after a single plasma exchange session. She was discharged
      by the third day of admission without any complications. According to current
      literature, our patient is the fifth patient treated with plasma exchange to be
      the subject of a publication.

PMID- 19379155
TI  - A case report of successful long-term relapse control by protein-a
      immunoadsorption in an immunosuppressive-treated patient with end-stage renal
      disease due to Wegener's granulomatosis.
AB  - A long-term female hemodialysis patient with end-stage renal disease due to
      Wegener's granulomatosis (WG) experienced a severe relapse when immunosuppressive
      therapy was switched from prednisone and cyclophosphamide to azathioprine
      maintenance therapy. Ten courses of protein A immunoadsorption therapy and
      switching immunosuppressive therapy to mycophenolate mofetil have proved to be
      very successful and free of side effects. The patient has fully recovered from
      all clinical WG symptoms and is still in remission ten months after the
      treatment.

PMID- 19379156
TI  - Case reports of the use of immunoadsorption or plasma exchange in high-risk
      pregnancies of women with antiphospholipid syndrome.
AB  - Conventional treatment of antiphospholipid syndrome (APS) pregnancies with
      aspirin and/or heparin is sometimes unable to counteract maternal and/or fetal
      complications. In this article we report the cases of two patients who were
      unresponsive to conventional treatment for APS during their first pregnancy, and
      who were treated in the following pregnancy with plasma exchange and
      immunoadsorption respectively, in addition to conventional therapy. Both patients
      had a history of thrombotic events, a previous pregnancy loss at the 11th week of
      gestation and the same antiphospholipid antibody profile (lupus anticoagulant
      activity and high titers of immunoglobulin G (IgG) anti-beta2 glycoprotein I and
      IgG anticardiolipin antibodies). Patient 1 was treated from the fourth week of
      her second pregnancy with weekly plasma exchange. Due to fetal growth restriction
      and oligohydramnios in the 26th week she delivered, by cesarean section, a
      healthy female infant weighing 730 g who survived. Patient 2 was treated from the
      seventh week of her second pregnancy with twice a week protein A
      immunoadsorption. The pregnancy proceeded normally until the 36th week, when, due
      to slight intrauterine growth restriction, she delivered a healthy baby girl
      weighing 2375 g by cesarean section. Anti-beta2 glycoprotein I antibody trends
      were similar during both types of treatment. On the basis of our findings
      obtained from only two cases it is impossible to define the best aphaeretic
      treatment of APS high risk pregnancies. Nevertheless, as a whole these data
      suggest better disease control using the immunoadsorption technique as compared
      to plasma exchange, despite their apparently similar anti-beta2 glycoprotein I
      antibody removal capabilities.

PMID- 19379157
TI  - Standard on microbiological management of fluids for hemodialysis and related
      therapies by the Japanese Society for Dialysis Therapy 2008.
AB  - The Committee of Scientific Academy of the Japanese Society for Dialysis Therapy
      (JSDT) proposes a new standard on microbiological management of fluids for
      hemodialysis and related therapies. This standard is within the scope of the
      International Organization for Standardization (ISO), which is currently under
      revision. This standard is to be applied to the central dialysis fluid delivery
      systems (CDDS), which are widely used in Japan. In this standard, microbiological
      qualities for dialysis water and dialysis fluids are clearly defined by endotoxin
      level and bacterial count. The qualities of dialysis fluids were classified into
      three levels: standard, ultrapure, and online prepared substitution fluid. In
      addition, the therapeutic application of each dialysis fluid is clarified. Since
      high-performance dialyzers are frequently used in Japan, the standard recommends
      that ultrapure dialysis fluid be used for all dialysis modalities at all dialysis
      facilities. It also recommends that the dialysis equipment safety management
      committee at each facility should validate the microbiological qualities of
      online prepared substitution fluid.

PMID- 19379164
TI  - Ratio of platelet reduction is an early predictive factor for the effectiveness
      of leukocytapheresis for ulcerative colitis patients.
AB  - Leukocytapheresis is effective for ulcerative colitis (UC), and both peripheral
      leukocyte and platelet counts decrease during apheresis. While leukocyte counts
      increase and overshoot after finishing the apheresis procedure, platelet
      reduction continues even after apheresis. The aim of this study is to elucidate
      the impact of the overshoot of leukocyte and continuous platelet reduction on the
      efficacy of leukocytapheresis for UC. Leukocyte and platelet counts before and
      one hour after each leukocytapheresis session of 43 UC cases were examined (31
      entered remission, but 12 did not). The correlation between the efficacy of
      leukocytapheresis and leukocyte overshoot or platelet reduction was examined. The
      average increase ratio of leukocytes in the initial five sessions of the
      responders was not significantly different from that of the non-responders (95%
      vs. 92%, P = 0.28). In contrast, the average decrease ratio of platelets in the
      initial five sessions of the responders was significantly higher than that of the
      non-responders (34% vs. 27%, P = 0.0041). Moreover, the platelet reduction at the
      third and fourth apheresis sessions in the responders was remarkably greater than
      that in the non-responders (33% vs. 20%, P = 0.0018). The efficiency of platelet
      reduction could be a predictive factor for the efficacy of leukocytapheresis.

PMID- 19379165
TI  - Feasibility of five days of consecutive leukocytapheresis for the treatment of
      ulcerative colitis: a preliminary study.
AB  - Leukocytapheresis (LCAP) has been applied for the treatment of steroid refractory
      ulcerative colitis (UC). A standard protocol employs one or two sessions of LCAP
      per week. Our aim was to determine whether five consecutive LCAP sessions can be
      performed safely and effectively for UC patients. Six patients with moderately
      active UC were enrolled. The patients received five days of consecutive LCAP in
      which the processing volume of blood was limited to 1500 mL per session. The
      hemoglobin levels in each patient gradually decreased, and the platelet count by
      the fifth session reached half of the value before the first session. The
      clinical activity index in two patients improved daily, and they went into
      remission with an improvement in the colonic endoscopic appearance after one
      week. This preliminary study showed that five consecutive LCAP sessions are safe
      and feasible for active UC patients. The therapeutic efficacy and suitable
      patients for this treatment protocol should be confirmed by further studies.

PMID- 19379166
TI  - Selective removal of bisphenol A from serum using molecular imprinted polymer
      membranes.
AB  - Bisphenol A (BPA)-imprinted membranes were prepared by hybridization of a porous
      polysulfone (PSu) scaffold with a BPA-imprinted polymer powder copolymerized with
      dimethacrylate BPA and divinylbenzene. When exposed to a donor calf serum (DCS)
      solution containing 0.05-100 microM of BPA, the imprinted hybrid membrane (10 x
      10 mm(2)) bound BPA at a capacity of 6.0 x 10(-9)-20 x 10(-6) mol/g-membrane. In
      contrast, a similar sized powder-free PSu membrane bound BPA at a capacity of
      only 1.5 x 10(-9)-1.9 x 10(-6) mol/g-membrane. The difference in the binding
      capacities of the two membranes was attributed to the BPA-imprinted powder
      hybridized in the PSu membrane. Clinical analyses confirmed that the DCS
      parameters remained nearly constant before and after the BPA binding. This
      observation suggests that BPA was removed selectively from the DCS solution by
      the imprinted hybrid membrane. Together, these results demonstrate that the
      molecular imprinting technique is very useful as a novel medical material
      adsorbent that can reduce exposure to the endocrine disruptor, BPA.

PMID- 19379167
TI  - Direct hemoperfusion with a beta2-microglobulin-selective adsorbent column
      eliminates inflammatory cytokines and improves pulmonary oxygenation.
AB  - Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are
      characterized by a high mortality rate; therefore, ARDS/ALI in humans is a
      leading cause of morbidity and mortality in critically ill patients. As
      previously reported, cytokines play a critical role as signaling molecules that
      initiate, amplify, and perpetuate inflammatory responses on a local and systemic
      basis, and the polymyxin-B immobilized direct hemoperfusion system (PMX-DHP) is
      effective for the treatment of ARDS/ALI. Furthermore, another direct
      hemoperfusion system using the beta2-microglobulin-selective adsorbent column,
      Lixelle, the direct hemoperfusion treatment (Lixelle-DHP), has been applied in
      some cases to patients who are affected with systemic inflammatory response
      syndrome. The aim of this study is to evaluate the therapeutic efficacy of
      Lixelle-DHP in the treatment of ARDS/ALI. Four patients, aged 67-79 years old
      (mean 72 +/- 6.2 years), diagnosed with ARDS/ALI were treated with Lixelle-DHP.
      The P(a)O(2)/fraction of inspired oxygen (F(i)O(2)) ratio (PF ratio) was 90.0 +/-
      22.9 before the treatment, and it increased to 129.9 +/- 5.6 at 72 h afterward
      the start of treatment. Inflammatory cytokines such as interleukin (IL)-1 beta,
      IL-6, soluble intercellular adhesion molecule 1 (sICAM-1) decreased significantly
      after the treatment. All patients were still alive after one month. However,
      while IL-2 had decreased significantly after the treatment, it had returned by
      the next treatment. It is possible that Lixelle-DHP might be able to improve the
      PF ratio and mortality rate as a result of decreased cytokines, and it has been
      suggested that Lixelle-DHP has a beneficial influence in the treatment of
      ARDS/ALI.

PMID- 19379168
TI  - Nanobiotechnology for the prevention of dialysis-related amyloidosis.
AB  - Dialysis-related amyloidosis is related to the inefficient removal of beta(2)
      microglobulin (beta(2)-m) that is mainly responsible for the formation of amyloid
      fibrils deposited on the joints and in the heart, blood vessels and digestive
      system. Magnetically assisted hemodialysis (MAHD) can be used for the prevention
      of dialysis-related amyloidosis. MAHD is based on ferromagnetic nanoparticle
      targeted binding substance conjugates (FN-TBS Cs) that should be administered to
      the patient before the dialysis session. The TBS should have a high affinity for
      beta(2)-m so that the conjugates bind with the beta(2)-m in the bloodstream. The
      complex FN-TBS-beta(2)-m will be selectively removed during dialysis by means of
      a "magnetic dialyzer" that is installed at the dialysis machine in series to the
      conventional dialyzer. We have examined the in vitro applicability of MAHD by
      employing biocompatible Fe(3)O(4) and bovine serum albumin (BSA) as constituents
      of the FN-TBS Cs. We evaluated the binding capacity of both bare Fe(3)O(4) FNs
      and Fe(3)O(4)-BSA Cs for beta(2)-m concentrations ranging from mild to severe
      conditions. Finally, we conducted mock-dialysis experiments for the evaluation of
      several technical issues related to MAHD. beta(2)-m is adsorbed onto the
      Fe(3)O(4)-BSA Cs not only almost instantly, but also very efficiently. The
      employed Cs do not chemically interact with the materials used in standard
      dialyzers, as agglomerates were not observed in the capillaries of the
      conventional dialyzers. MAHD may become an efficient modality for the prevention
      of dialysis-related amyloidosis because beta(2)-m concentrations ranging from
      mild to severe conditions can be adequately handled.

PMID- 19379169
TI  - Effect of sevelamer hydrochloride on bone in experimental uremic rats.
AB  - Hyperphosphatemia in dialysis patients is known to cause secondary
      hyperparathyroidism and high-turnover bone disease. Sevelamer hydrochloride
      (sevelamer) is a nonabsorbed, calcium-free phosphate-binder. We determined the
      effect of sevelamer on parathyroid hormone (PTH)-induced high bone turnover. Rats
      were sham-operated or 5/6-nephrectomized (Nx) and fed a phosphate loading diet
      for 16 weeks or 5/6-nephrectomized and fed a phosphate loading diet for 8 weeks
      and then fed the same diet containing 3% sevelamer for the subsequent 8 weeks (Nx
      S). Sevelamer significantly reduced serum PTH. The relative osteoid volume
      (OV/BV), osteoid surface (OS/BS), eroded surface (ES/BS), mineral appositional
      rate (MAR), volume-referent bone formation rate (BFR/TV), and bone-referent bone
      formation rate (BFR/BV) were measured for vertebral bone histomorphometric
      analysis. All parameters were statistically higher in the Nx rats than in the
      sham-operated control rats. The administration of sevelamer attenuated increases
      in OV/BV, ES/BS, BFR/TV, and BFR/BV. For femur histomorphometric analysis, the
      porosity area (%) (PoAr/CtAr), osteoid surface on the periosteal surface, osteoid
      surface on the endocortical surface (OS/Es), mineral appositional rate on the
      periosteal surface, mineral appositional rate on the endocortical surface, bone
      formation rate on the periosteal surface, and bone formation rate on the
      endocortical surface (Es BFR) were calculated. All parameters were higher in the
      Nx group than in the control group. Sevelamer inhibited the elevation of
      PoAr/CtAr, OS/Es, and Es BFR. Our findings suggest that the decrease in PTH by
      sevelamer may be beneficial in the treatment of high PTH-induced bone disease.

PMID- 19379170
TI  - Regulatory effect of parathyroid hormone on sRANKL-osteoprotegerin in
      hemodialysis patients with renal bone disease.
AB  - Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin
      are newly identified molecules that contribute to the modulation of bone
      remodeling. RANKL activates osteoclast function by binding to RANK in either a
      soluble or membrane-bound form, whereas osteoprotegerin (OPG) neutralizes its
      effects. The aim of this study is the evaluation of soluble RANKL (sRANKL)-OPG in
      cohorts of hemodialysis patients and the establishment of possible correlations
      between their serum levels and those of other biochemical markers. We measured
      intact parathyroid hormone (iPTH), osteocalcin (OC), OPG, alkaline phosphatase
      (ALP), tartrate-resistant acid phosphatase (TRAP) and sRANKL in 104 hemodialysis
      patients. The patients were studied as a whole and in two subgroups according to
      their bone turnover state. In patients with low serum levels of bone turnover
      markers (intact parathyroid hormone [iPTH] < 100 pg/mL, ALP < 100 U/L, TRAP < 4
      U/L; 33 patients), the following correlations were found: (i) positive
      correlations of iPTH with RANKL (r = 0.394, P = 0.023) and RANKL/OPG ratio (r =
      0.49, P = 0.004); (ii) a negative correlation between iPTH and OPG (r = -0.365, P
      = 0.037). The subgroup of patients with normal or high serum levels of bone
      turnover markers (iPTH >or= 150 pg/mL, ALP >or= 100 U/L, OC >or= 40 ng/mL; 19
      patients) exhibited the following significant correlations: (i) a positive
      correlation between OPG and iPTH serum level (r = 0.649, P = 0.003); and (ii) a
      negative correlation between RANKL/OPG ratio and iPTH (r = -0.464, P = 0.045). In
      conclusion, the observation that PTH favors RANKL and inhibits OPG production was
      only demonstrated in the serum of hemodialysis patients in a low turnover state.
      The positive correlation between serum OPG and iPTH in normal or high turnover
      rates implies a homeostatic mechanism to limit bone resorption, probably
      associated with skeletal resistance to PTH.

PMID- 19379171
TI  - On-line hemodiafiltration in Southeast Asia: a three-year prospective study of a
      single center.
AB  - Growing evidence suggests the superiority of on-line hemodiafiltration (HDF)
      compared with the conventional hemodialysis technique in many aspects; however,
      on-line HDF is still not used worldwide, including in Southeast Asia. The purpose
      of this study is to compare various clinical outcomes between on-line HDF and
      high-flux hemodialysis (HFHD). This was a single-center three-year prospective
      observational study that demonstrated the clinical parameters after switching
      from HFHD to on-line HDF in 22 HDF patients, whose average age was 58.1 +/- 13.3
      years. The incidence of intradialytic undesired events, including hypotension,
      decreased and an apparent increase in appetite and an improvement in overall well
      being were recorded by most patients after switching to on-line HDF. The data for
      dry weight, body mass index, and normalized protein nitrogen appearance, which
      represent nutritional status, showed a significant improvement while still
      maintaining a satisfactory albumin level. The adequacy in terms of urea reduction
      ratio significantly increased. The serum predialysis beta(2)-microglobulin levels
      were reduced by 25.7% from 31.1 +/- 3.1 to 23.1 +/- 4.8 mg/L (P < 0.05) at six
      months and remained constant during the three years of follow-up. The patients'
      lipid profile was well controlled, and the mean C-reactive protein value was
      still maintained in the normal range. In conclusion, our three-year experience
      showed that on-line HDF is a well-tolerated treatment with a lower incidence of
      intradialytic undesired events. The potential benefits may include the effective
      removal of higher molecular weight uremic toxins and an improved nutritional
      status, along with a low inflammatory state.

PMID- 19379172
TI  - Hemofiltration with the Cascade system in an experimental porcine model of septic
      shock.
AB  - High-volume hemofiltration (HVHF) has been suggested as an adjuvant treatment of
      septic shock because of its capacities to remove inflammatory mediators from
      blood. Nevertheless, HVHF presents some important drawbacks, such as the
      depletion of low molecular weight molecules (nutriments, vitamins, trace elements
      and antibiotics) due to the high ultrafiltration rate, or the significant
      financial cost and nursing workload due to the frequent changes of large amounts
      of expensive sterile substitution fluids. A new hemofiltration system called
      "Cascade" has been developed, allowing very high ultrafiltration rates (120
      mL/kg/h) limiting these drawbacks by using a special extracorporeal circuit. The
      objective of this study was to assess the technical feasibility of the Cascade
      system and to compare its hemodynamic impact to that of the standard HVHF system.
      Twenty sepsis-induced pigs were randomized in two groups: one group was
      hemofiltered with the standard HVHF system and the other with the Cascade system
      during a six-hour session. No technical problems were observed with the Cascade
      system during the experiment. At the end of the experiment, colloid requirements
      (989 +/- 355 mL vs. 1913 +/- 538 mL, P = 0.006), epinephrine requirements (0.82
      +/- 0.42 mg vs. 3.27 +/- 3.02 mg, P < 0.001), lactic acidosis (pH = 7.33 +/- 0.08
      vs. 7.10 +/- 0.07, P < 0.001) and mean pulmonary arterial pressure were less
      pronounced in the Cascade group. These results suggest that Cascade
      hemofiltration is technically feasible and safe. Moreover, compared with standard
      HVHF, it can reduce the severity of porcine septic shock.

PMID- 19379173
TI  - A case report of successful treatment with plasma exchange for hemophagocytic
      syndrome associated with severe systemic juvenile idiopathic arthritis in an
      infant girl.
AB  - An infantile case of hemophagocytic syndrome (HPS) with systemic juvenile
      idiopathic arthritis (s-JIA), refractory to methylprednisolone pulse therapy and
      cyclosporine A administration, was successfully treated by plasma exchange. The
      patient was a one-year-old Japanese girl who had developed recurrent steroid
      dependent signs, including fever, skin eruption, and hepatopathy, while in
      France, where she had been diagnosed as having s-JIA at eight months of age. As a
      high fever and rheumatoid rash were evident on arrival at our hospital, she was
      admitted and given intravenous methylprednisolone pulse therapy and cyclosporine
      A. She developed pancytopenia with a generalized clonic seizure, high fever, and
      liver dysfunction after her cytomegalovirus (CMV) titer became positive during
      the course of treatment; therefore, she was treated with ganciclovir. She was
      subsequently diagnosed as having HPS complicating s-JIA from the findings of a
      bone marrow aspirate. At this time, her blood examination data including a high
      level of C-reactive protein and hyperferritinemia, suggested that her s-JIA was
      very active, and the pancytopenia continued after her CMV titer became negative.
      Therefore, CMV infection against a background of active s-JIA could have
      triggered the HPS in this case. Because the HPS was resistant to an
      immunosuppressive regime of methylprednisolone pulse therapy and cyclosporine A,
      plasma exchange therapy was started. After three sessions of this therapy, the
      patient's symptoms and laboratory data were markedly improved. Our experience
      suggests that plasma exchange should be considered as a therapeutic tool for HPS
      refractory to conventional therapy.

PMID- 19379174
TI  - A case report of steroid-resistant antineutrophil cytoplasmic antibody-related
      vasculitis successfully treated by mizoribine in a hemodialysis patient.
AB  - Mizoribine (MZR) has shown to be effective against antineutrophil cytoplasmic
      antibody (ANCA)-related vasculitis; however, no reports have described the
      successful treatment of steroid-resistant ANCA-related vasculitis with MZR in
      patients with renal insufficiency requiring hemodialysis. We herein report the
      case of a 39-year-old man undergoing hemodialysis in whom MZR successfully
      lowered the myeloperoxidase (MPO)-ANCA titer accompanied by remission of
      interstitial pneumonia, together with the pharmacokinetics of MZR. The patient
      developed severe renal insufficiency and interstitial pneumonia, and was started
      on hemodialysis. Although prednisolone was administered followed by azathioprine,
      the MPO-ANCA level and interstitial pneumonia showed insufficient improvement.
      Azathioprine was replaced by MZR and the administered dose of MZR was determined
      by measuring serum concentrations of MZR at the start of the dialysis session;
      this was because we confirmed that MZR could only be removed via dialysis, and
      that the serum concentration of MZR was maintained until the next dialysis
      session. The maintenance dose was finally set at MZR 75 mg after each dialysis.
      Subsequently, the ANCA titer decreased and interstitial pneumonia resolved
      without any MZR-related side effects. This case demonstrates that MZR is safe and
      effective, even in patients with steroid-resistant ANCA-related vasculitis
      undergoing hemodialysis, and can be monitored by measuring serum concentrations
      of MZR.

PMID- 19379175
TI  - A case report of darbepoetin treatment in a patient with sickle cell disease and
      chronic renal failure undergoing regular hemodialysis procedures that induce a
      dose-dependent extension of blood transfusion intervals.
AB  - In this case, a female Nigerian patient suffered from sickle cell disease (SCD,
      hemoglobin SS)-induced chronic renal failure and was undergoing hemodialysis
      treatment. Due to SCD crisis and renal anemia the patient received regular blood
      transfusions when the hemoglobin concentration fell below 5.0 g/L. Blood
      transfusion associated iron-overload was noticed. To reduce the iron-overload
      side effects, we started an erythropoietin therapy (darbepoetin) to extend the
      blood transfusion interval, using 30-150 microg/week. As a result of our
      investigation we observed that darbepoetin can significantly extend blood
      transfusion intervals without increasing SCD crisis. To substantiate our
      observation, further investigations are needed with more SCD patients undergoing
      regular hemodialysis treatment.

PMID- 19379176
TI  - A case report of a bone histomorphometrical analysis after a total
      parathyroidectomy.
AB  - A patient with secondary hyperparathyroidism (2 degrees HPT) underwent a total
      parathyroidectomy (PTx) without autotransplantation and showed interesting
      changes in the morphology of his iliac bone before and after the surgery. A 70
      year-old man had been on hemodialysis for chronic glomerulonephritis since 1987.
      He had been administered calcium carbonate 6.0 g daily to prevent reabsorption of
      phosphorus and alfacalcidol 1.0 microg three times weekly at the end of
      hemodialysis. In September 2000, his intact parathyroid hormone (iPTH; 1-84 PTH)
      was 610 pg/mL; therefore, from 2.5 microg to 10 microg 22-oxacalcitriol
      (maxacalcitol, a derivative of active vitamin D) was administered intravenously
      three times weekly at the end of hemodialysis. This compound is used in Japan for
      2 degrees HPT. However, the iPTH progressed, and hypercalcemia and
      hyperphosphatemia were observed. Ultrasonography of the neck illustrated three
      enlarged parathyroid glands that were each over 1.0 cm in diameter. On 14 July
      2004, a PTx without autotransplantation (PTx alone) and an iliac crest bone
      biopsy were performed. Bone specimens showed mild lesions of hyperparathyroidism,
      but did not meet the criteria for osteitis fibrosa. One year after the procedure,
      a second biopsy was obtained to investigate the bone turnover in response to a
      lack of parathyroid hormone. The bone specimen showed tetracycline labeling at
      the time of PTx alone, and new bone apposition on the surface without
      tetracycline labeling. This adynamic bone disease (ABD) suggested that new bone
      apposition in the absence of tetracycline labeling had occurred after the PTx
      alone, and it had likely occurred over the course of one year.

PMID- 19379177
TI  - International Veterinary Cancer Meetings 2003.

PMID- 19379178
TI  - Treatment of vascular and soft-tissue sarcomas in dogs using an alternating
      protocol of ifosfamide and doxorubicin.
AB  - A retrospective analysis was done to assess the toxicity and efficacy associated
      with an alternating chemotherapy protocol of ifosfamide (375 mg m(-2)) and
      doxorubicin (30 mg m(-2)) for adjuvant treatment of 39 dogs with sarcomas. Twelve
      dogs had various soft-tissue sarcomas and 27 dogs had hemangiosarcoma (HSA).
      Complete blood counts were evaluated 7 days after the first dose of ifosfamide
      and doxorubicin. One dog had grade 4 neutropenia (<500 microL(-1)) after
      treatment with ifosfamide and one dog had grade 3 neutropenia (500-1000 microL(
      1)) after treatment with doxorubicin. One dog treated with doxorubicin was
      hospitalized for 24 h due to vomiting. The median survival time (ST) for the 27
      dogs with HSA treated by surgery and with doxorubicin/ifosfamide was 149 days
      (mean 366 days). Although the protocol of alternating ifosfamide and doxorubicin
      was well tolerated, it failed to result in a statistically significant
      improvement in the ST when compared to a historical population of dogs with stage
      2 splenic HSA treated by surgery alone.

PMID- 19379179
TI  - A combination chemotherapy protocol with MOPP and CCNU consolidation (Tufts
      VELCAP-SC) for the treatment of canine lymphoma.
AB  - A chemotherapy protocol using a consolidation phase of alkylating agents was used
      for treating 94 dogs with lymphoma. Fifty-seven percent of dogs were in stage V,
      63% were ill and 38% had T-cell lymphoma. The complete remission (CR) rate was
      70% and is comparable to results achieved with previously published chemotherapy
      protocols. Anorexia predicted the remission; of the 40 dogs without anorexia, 35
      (88%) achieved CR whereas of 52 dogs with anorexia, 30 (58%) achieved CR. Median
      first CR duration was 168 days and 1- and 2-year CR rates were 17.4 and 15.5%,
      respectively. Platelet count affected length of first CR, with a 53.2% reduced
      chance of coming out of remission with each log increase in platelet count.
      Median survival time was 302 days. One and 2-year survival rates were 44 and 13%,
      respectively. Anorexia and no dose reduction of any drug were independent
      negative variables. Of 93 dogs with toxicity data, 65 dogs (70%) required a dose
      reduction. Cyclophosphamide was most commonly reduced with reductions in 31 (38%)
      of 82 dogs. A dose reduction was significantly more likely in dogs with B-cell
      lymphoma than in those with T-cell lymphoma.

PMID- 19379180
TI  - Treatment of unresectable hepatocellular adenoma in dogs with transarterial
      iodized oil and chemotherapy with and without an embolic agent: a report of two
      cases.
AB  - Transarterial iodized oil with chemotherapy was evaluated in two dogs with large,
      surgically unresectable hepatocellular adenoma. A single cycle of therapy was
      used in each dog. Chemoembolic mixtures varied: doxorubicin emulsified with
      iodized oil radiographic contrast (case 1), doxorubicin and mitomycin C
      emulsified with iodized oil radiographic contrast (case 2). In addition, dog 2
      underwent arterial embolization with polyvinyl alcohol granules. Response was
      assessed by computed tomography at 1 and 3 months after treatment. Superselective
      catheterization of the hepatic arterial branch supplying the tumour was not
      achieved in either case. In the immediate post-operative period, both dogs
      developed mild clinical signs that may have been consistent with post
      embolization syndrome, but neutropenia and reduced liver function were not
      observed. Tumour response was minimal: stable disease at 1 month and progressive
      disease at 3 months was observed in both cases.

PMID- 19379181
TI  - Breed incidence of lymphoma in a UK population of insured dogs.
AB  - Canine lymphoma is one of the commonest forms of spontaneous canine neoplasia.
      Improved understanding of the genetic and environmental risk factors for canine
      lymphoma, including breed differences, may have comparative benefits for the
      study of non-Hodgkin's lymphoma in humans. In this study, data from a pet
      insurance company were used to estimate the incidences of canine lymphoma for
      pedigree breeds in the UK. Out of a total of 130,684 insured dogs, 103 had a
      diagnosis of lymphoma recorded. A significant breed effect was found with the
      boxer, bulldog and bull mastiff breeds, all having a high incidence of lymphoma.
      The small number of lymphoma cases recorded may have limited our ability to
      detect other breeds with an elevated risk. Incidence of lymphoma was found to
      increase with age, peaking at 10 years of age.

PMID- 19379182
TI  - The bisphosphonates alendronate and zoledronate are inhibitors of canine and
      human osteosarcoma cell growth in vitro.
AB  - Bisphosphonates (BPs) are a class of non-hydrolysable analogues of pyrophosphate
      that have high affinity for bone mineral and are inhibitors of bone resorption.
      The in vitro effects of two nitrogen-containing BPs, alendronate (ALE) and
      zoledronate (ZOL), on growth, induction of apoptosis and effects on cell-cycle
      distribution in two canine and two human osteosarcoma (OSA) cell lines are
      investigated here. Both significantly (P < 0.001) reduced cell growth in all cell
      lines, as assessed by a colorimetric assay with IC(50) values in the range of 7.3
      61.4 microM and 7.9-36.3 microM for ALE and ZOL, respectively. Both BPs caused a
      significant (P < 0.001) dose-dependent increase in the proportion of cells
      undergoing apoptosis, as assessed both by cell-cycle analysis and by annexin-V
      binding. Both ALE and ZOL altered the proportion of cells in each phase of the
      cell cycle, but the extent and proportion was both drug and cell line dependent.
      These data indicate that the nitrogen-containing BPs have direct anti-tumour
      activity against canine and human OSA cells.

PMID- 19379183
TI  - Influence of honey bee products on transplantable murine tumours.
AB  - The effect of propolis [it is a water-soluble derivative (WSDP)] and related
      polyphenolic compounds of propolis (caffeic acid, caffeic acid phenethyl ester
      and quercetin), honey, royal jelly and bee venom on tumour growth, metastasizing
      ability and induction of apoptosis and necrosis in murine tumour models (mammary
      carcinoma and colon carcinoma) was investigated. WSDP and related polyphenolic
      compounds showed significant anti-metastatic effect (P < 0.01 and P < 0.001)
      given either before or after tumour-cell inoculation. Oral or systemic
      application of WSDP or caffeic acid significantly reduced subcutaneous tumour
      growth and prolonged the survival of mice. Honey also exerted pronounced anti
      metastatic effect (P < 0.05) when applied before tumour-cell inoculation (peroral
      2 g kg(-1) for mice or 1 g kg(-1) for rats, once a day for 10 consecutive days).
      Royal jelly did not affect metastasis formation when given intraperitoneally or
      subcutaneously. However, intravenous administration of royal jelly before tumour
      cell inoculation significantly (P < 0.05) inhibited metastasis formation. When
      mice were given 10(5) tumour cells intravenously immediately after bee venom
      injection, the number of tumour nodules in the lung was significantly lower (P <
      0.001) than in untreated mice or mice treated with bee venom subcutaneously.
      Local presence of bee venom in the tissue caused significant delay in
      subcutaneous tumour formation. These findings clearly demonstrate that anti
      tumour and anti-metastatic effects of bee venom are highly dependent on the route
      of injection and on close contact between components of the bee venom and tumour
      cells. These data show that honey bee products given orally or systemically may
      have an important role in the control of tumour growth and tumour metastasizing
      ability.

PMID- 19379184
TI  - Hypertrophic osteopathy secondary to pulmonary sarcoma in a cat.
AB  - A case of hypertrophic osteopathy secondary to a pulmonary spindle cell sarcoma
      is described. The 9-year-old male cat presented with a 1-month history of
      decreased appetite, decreased activity and progressive lameness with swelling and
      pain of all four limbs. Thoracic radiographs showed a soft tissue opaque mass in
      the left caudal lung lobe. Radiographs of all limbs showed extensive periosteal
      new bone formation of uniform opacity demonstrating a 'palisading' pattern. The
      lung mass was removed at exploratory thoracotomy; histopathological examination
      diagnosed a low-grade spindle cell sarcoma. Prior to surgery, the cat had a non
      specific conjunctivitis that resolved spontaneously following lobectomy raising
      the possibility of a paraneoplastic association. The lameness also resolved; six
      months after surgery, the periosteal palisading of new bone on the long bones had
      remodelled, and there was no evidence of pulmonary metastases.

PMID- 19379185
TI  - Ocular metastasis of a vaccine-associated fibrosarcoma in a cat.
AB  - A 6-year-old, neutered male domestic shorthair cat was evaluated for a recurrent
      vaccine-associated fibrosarcoma. The cat had three excisions of the tumour prior
      to presentation and was referred for radiation therapy. Ten months following
      treatment with radiation therapy, the cat was presented again for a cloudy
      appearance to the eye. An exenteration was performed, and biopsy revealed
      fibrosarcoma. At the same time, two discrete pulmonary nodules were identified on
      thoracic radiographs. Two doses of doxorubicin (20 mg/m(2)) and cyclophosphamide
      (100 mg/m(2)) were administered intravenously 3 weeks apart. Despite treatment,
      the pulmonary nodule doubled in size. This case represents the first antemortem
      report of ocular metastasis of a vaccine-associated sarcoma and supports the
      highly aggressive nature of these tumours.

PMID- 19379186
TI  - Trends in veterinary cancer imaging.
AB  - With the recent advances in diagnostic imaging technology, cancer imaging in
      veterinary medicine has become more specific for disease diagnosis, more accurate
      for determining tumour margins and more sensitive for detecting metastatic
      disease. Ultrasound provides highly detailed images of parenchymal masses and
      infiltrative lesions while providing a means for aspiration or biopsy using real
      time image guidance. Computed tomography and magnetic resonance-imaging
      techniques provide exquisite anatomical resolution that improves diagnostic
      accuracy, provides an accurate means of radiation or surgical treatment planning
      and a quantitative means for monitoring response to therapy. In addition to
      traditional anatomic imaging, new techniques are being developed for estimating
      functional parameters such as tumour perfusion, cell metabolism and gene
      expression. While conventional planar scintigraphy has been available for some
      time, newer nuclear imaging modalities such as positron emission tomography
      promise to further improve the accuracy of initial tumour diagnosis and staging
      and determination of response to therapy. Although many of these functional
      techniques are not yet clinically available, it is highly likely that some will
      be integrated into routine clinical practice in the near future.

PMID- 19379187
TI  - Results from the treatment of advanced stage squamous cell carcinoma of the nasal
      planum in cats, using a combination of intralesional carboplatin and superficial
      radiotherapy: a pilot study.
AB  - Six cats with an advanced stage squamous cell carcinoma (SCC) of the nasal planum
      were treated with a combination of superficial radiotherapy and intralesional
      carboplatin therapy. This multimodality protocol was well tolerated by the
      majority of cats and resulted in complete responses in all cats (100%). Median
      follow-up for all cats is 268 days, and the median time-to-recurrence, time-to
      progression and overall survival have not yet been reached. Our study, although
      limited in number of animals and with a relatively short median follow-up
      compared to other studies for this disease, suggests that a combination of
      radiotherapy and intralesional carboplatin is a useful treatment option for an
      advanced stage SCC of the nasal planum in cats and warrants further application
      of the multimodality approach presented here.

PMID- 19379188
TI  - Development of a two-antibody model for the evaluation of copper-64
      radioimmunotherapy.
AB  - Copper-64 emits beta(+) and beta(-) particles suitable for positron emission
      tomography and radioimmunotherapy (RIT) of cancer. Copper-64-labelled antibodies
      have caused complete responses in laboratory animal RIT studies at far lower
      radiation doses than traditionally prescribed. The intracellular localization of
      copper radioisotopes may lead to cytotoxic effects by mechanisms beyond ionizing
      radiation damage. The purpose of this research was to develop a model using both
      internalizing and non-internalizing antibodies for direct comparison in future
      RIT studies using the same animal model of cancer. The monoclonal antibodies,
      cBR96 and cT84.66, were conjugated with N-hydroxysulfosuccinimidyl DOTA. All
      conjugates retained high immunoreactivity and labelled efficiently with (64)Cu
      with high specific activity and radiochemical purity. Twenty-four hour
      biodistributions determined in LS174T tumour-bearing nude mice demonstrated low
      organ and high tumour uptakes for both monoclonal antibodies. This model
      constitutes a promising system for elucidating whether internalization of (64)Cu
      is responsible for an enhanced tumour cytotoxicity in vivo.

PMID- 19379189
TI  - Feline epitheliotrophic T-cell lymphoma with paraneoplastic eosinophilia -
      immunochemotherapy with vinblastine and human recombinant interferon alpha(2b).
AB  - A cat with epitheliotrophic T-cell lymphoma with paraneoplastic eosinophilia is
      described. Initial attempts to control the disease with conventional therapies
      failed. The addition of recombinant human interferon alpha(2b) (rhINFalpha(2b))
      resulted in a clinical, haematogenous and sonographic improvement for 49 days.
      The overall survival time from initial diagnosis was 100 days. Relapse was
      correlated with the development of serum antibodies directed against
      rhINFalpha(2b). To our knowledge, this is the first report describing the
      clinical use of IFNalpha in the treatment of neoplasia in the cat.

PMID- 19379208
TI  - Curative-intent radiation therapy as a treatment modality for appendicular and
      axial osteosarcoma: a preliminary retrospective evaluation of 14 dogs with the
      disease.
AB  - Canine osteosarcoma is a common bone malignancy associated with aggressive local
      disease and rapid metastasis. Current local therapeutic modalities do not provide
      curative-intent options for dogs with significant orthopaedic or neurologic
      disease, dogs which are denied amputation or dogs with non-resectable lesions.
      The goals of this retrospective study included the evaluation of local control,
      survival, and time to the development of metastases in 14 dogs treated with
      curative-intent radiation therapy and chemotherapy. Median local disease control
      was 202 days (79-777). Median survival was 209 days (79-781). Median time to
      metastasis was 314 days (7-645). No significant correlation was found between the
      outcome and pre-treatment alkaline phosphatase levels, radiographic appearance,
      tumour site, radiation dose or chemotherapeutics administered. In these dogs,
      full-course radiation therapy in conjunction with chemotherapy was not found to
      yield equivalent results to the standard of care options.

PMID- 19379209
TI  - Immunohistochemical detection of HER-2/neu expression in spontaneous feline
      mammary tumours.
AB  - Mammary gland tumours (MGT) are the third most common tumours in the cat. At
      least 85% are malignant and metastasis is common. The HER-2/neu protooncogene
      encodes a 185-kDa transmembrane tyrosine receptor kinase protein. Approximately
      25-30% of human MGT demonstrate HER-2/neu protein overexpression in the malignant
      cells, and overexpression has been associated with an increased metastatic
      propensity and a decreased prognosis. No reports have been published, to date,
      investigating the expression of Her-2/neu in cats or cats with spontaneous
      mammary tumours. Based on the increased percentage of malignant mammary cancers
      in cats, compared to that in dogs, and the correlation of an increased malignancy
      and a decreased prognosis with Her-2 overexpression in human mammary cancer, we
      hypothesized that cats with spontaneous malignant mammary adenocarcinoma
      overexpress Her-2/neu in the neoplastic mammary epithelial cells. Thirty cats
      with MGT were assayed for Her-2/neu immunohistochemical expression. The median
      percentage of cells from feline MGT expressing Her-2/neu by utilizing the Dako
      polyclonal and CB11 monoclonal antibodies was 85 and 92.5, respectively. Her
      2/neu expression intensity grades 2 and 3 consistent with the overexpression by
      utilizing the Dako polyclonal and CB11 monoclonal antibodies were observed in 90
      and 76.7% of cats with MGT, respectively. The level of overexpression concordance
      across the two antibodies was 70%. The results from this study suggest that Her
      2/neu overexpression is common in cats with spontaneous MGT, and therefore
      appears to represent an excellent model for Her-2/neu-overexpressing human breast
      cancer.

PMID- 19379210
TI  - Piroxicam and carboplatin as a combination treatment of canine oral non-tonsillar
      squamous cell carcinoma: a pilot study and a literature review of a canine model
      of human head and neck squamous cell carcinoma.
AB  - Results of the treatment with a combination of carboplatin and piroxicam in seven
      dogs with advanced non-tonsillar oral squamous cell carcinoma (SCC) were
      retrospectively analysed. This multi-agent protocol was well tolerated by all
      dogs and resulted in a complete regression of the tumour without additional
      surgery in four of seven patients. Additional surgery was necessary to remove a
      metastatic lymph node in one dog and residual tumour in a second dog, which
      achieved a partial response following medical therapy. Median follow-up for all
      the dogs was 534 days, while the time-to-recurrence, time-to-progression and
      overall survival for this group of patients have not yet been reached. Our study,
      although limited in number of animals, suggests that this multiagent approach is
      a useful treatment option for oral non-tonsillar SCC in dogs and warrants wider
      application.

PMID- 19379211
TI  - Canine PHA-stimulated adherent cell enhance interferon-gamma production and
      proliferation of autologous peripheral blood mononuclear cells.
AB  - Dendritic cells are specialized antigen-presenting cells with immuno-modulating
      functions that are attractive for clinical applications for cancer immunotherapy.
      This study examined immunostimulatory functions of phytohemagglutinin (PHA)
      stimulated adherent cells (PHA-Ad cells) from peripheral blood mononuclear cells
      (PBMCs) in dogs. PHA-Ad cells enhanced interferon-gamma from autologous PBMC in
      vitro. PHA-Ad cells also stimulated antigen-independent proliferation of
      peripheral blood lymphocytes. These results suggest that PHA-Ad cells from PBMC
      possess a stimulatory function to evoke anti-tumour immunity and that they
      demonstrate potential for therapeutic applications in dogs.

PMID- 19379214
TI  - Characterization, expression and function of c-Met in canine spontaneous cancers.
AB  - Aberrant expression of the proto-oncogene c-Met has been noted in a variety of
      human cancers. To better define the potential role of Met dysregulation in canine
      cancer, the canine Met, hepatocyte growth factor (HGF) and HGF activator were
      cloned. Inappropriate expression of Met was present in canine tumour cell lines
      derived from a wide variety of cancers. Furthermore, both HGF and HGF activator
      were also expressed in several of these cell lines, providing evidence of a
      possible autocrine loop of Met activation. Stimulation of tumour cell lines with
      recombinant human HGF induced Met autophosphorylation, as well as activation of
      the downstream signalling elements Gab-1, Akt and Erk1/2. Scattering of tumour
      cells and migration across a defect occurred in response to HGF stimulation. The
      Met inhibitor PHA665752 blocked both HGF-induced phosphorylation of canine Met
      and HGF-mediated cell cycling, scattering and migration. These studies provide
      evidence that Met dysregulation may play a role in the biology of canine cancer
      and lay the groundwork for future studies employing Met inhibitors.

PMID- 19379215
TI  - Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of
      the urinary bladder.
AB  - Invasive transitional cell carcinoma (TCC) of the urinary bladder responds poorly
      to medical therapy. Combining platinum chemotherapy with a cyclooxygenase (cox)
      inhibitor has shown promise against canine TCC, where the disease closely mimics
      the human condition. A phase II clinical trial of carboplatin combined with the
      cox inhibitor, piroxicam, was performed in 31 dogs with naturally occurring,
      histopathologically confirmed, measurable TCC. Complete tumour staging was
      performed before and at 6-week intervals during therapy. Tumour responses in 29
      dogs included 11 partial remissions, 13 stable disease and five progressive
      disease. Two of the 31 dogs were withdrawn prior to the re-staging of the tumour.
      Gastrointestinal toxicity was observed in 23 dogs. Hematologic toxicity was noted
      in 11 dogs. The median survival was 161 days from first carboplatin treatment to
      death. In conclusion, carboplatin/piroxicam induced remission in 40% of dogs
      providing evidence that a cox inhibitor enhances the antitumour activity of
      carboplatin. The frequent toxicity and limited survival, however, do not support
      the use of this specific protocol against TCC.

PMID- 19379216
TI  - Survival analysis of one versus two treatments of local delivery cisplatin in a
      biodegradable polymer for canine osteosarcoma.
AB  - The purpose of this study was to evaluate one versus two doses of local delivery
      cisplatin in a biodegradable polymer (OPLA-Pt) for the treatment of osteosarcoma
      (OSA) after amputation in dogs. Medical records were reviewed retrospectively,
      and 105 dogs were included in the study; 39% of dogs received one treatment
      (surgical implantation) of OPLA-Pt and 61% of dogs received two treatments of
      OPLA-Pt after amputation. Administration of two doses of OPLA-Pt did not have a
      significant effect on disease-free interval or survival time compared to one
      dose. The anatomic site of the tumour was identified as a prognostic factor, and
      dogs with proximal humeral OSA had the shortest disease-free interval and
      survival times. There was no advantage to giving a second dose of local delivery
      cisplatin following amputation for the treatment of OSA in dogs.

PMID- 19379217
TI  - Different biological behaviour of Waldenstrom Macroglobulinemia in two dogs.
AB  - Waldenstrom Macroglobulinemia is a low-grade immunosecretory disorder associated
      with lymphoid tumours, which is rarely reported in veterinary medicine. In this
      study, we describe two clinical cases of this rare syndrome in dogs, each
      characterized by a different onset and clinical course. In one case, a hyperacute
      onset and aggressive behaviour of the neoplasm was observed. Absolute serum
      viscosity (SV) was retrospectively evaluated in order to explain clinical
      findings. Rotational viscosimetry showed good precision in measuring SV. Both
      dogs had SV values higher than a control groups of healthy dogs although only one
      subject developed hyperviscosity symptoms and complications. At high paraprotein
      concentrations, a slight reduction of the M-component was associated with a
      marked decrease in SV. Thus, this work suggests that SV assessment is a relevant
      tool for managing monoclonal gammopathies, whose usefulness should be further
      confirmed in larger cohorts of dogs.

PMID- 19379218
TI  - Parathyroid hormone-related peptide and hypercalcaemia in a dog with functional
      keratinizing ameloblastoma.
AB  - This case report describes a 6-year-old dog with oral ameloblastoma and
      hypercalcaemia. Serum parathyroid hormone-related peptide (PTH-rp) levels were
      high. No other cause for hypercalcaemia was found. The hypercalcaemia resolved
      after hemimandibulectomy. We are not aware of the previous description of canine
      oral ameloblastoma and hypercalcaemia mediated by PTH-rp. This case report
      suggests that PTH-rp stimulation of the PTH receptor may result in hypercalcaemia
      in dogs with oral ameloblastoma or other odontogenic neoplasms.

PMID- 19379219
TI  - SAHA and hemangiosarcoma: another view.

PMID- 19379227
TI  - Self and systems explorations in contemporary self psychology. Introduction.

PMID- 19379228
TI  - Some key features in the evolution of self psychology and psychoanalysis.
AB  - Psychoanalysis, as every science and its application, has continued to evolve
      over the past century, especially accelerating over the last 30 years. Self
      psychology has played a constitutive role in that evolution and has continued to
      change itself. These movements have been supported and augmented by a wide range
      of emergent research and theory, especially that of cognitive psychology, infant
      and attachment research, rapid eye movement and dream research, psychotherapy
      research, and neuroscience. I present schematically some of what I consider to be
      the key features of the evolution of self psychology and their interconnection
      with that of psychoanalysis at large, including the revolutionary paradigm
      changes, the new epistemology, listening/experiencing perspectives, from
      narcissism to the development of the self, the new organization model of
      transference, the new organization model of dreams, and the implicit and explicit
      dimensions of analytic work. I conclude with a focus on the radical ongoing
      extension of the analyst's participation in the analytic relationship, using, as
      an example, the co-creation of analytic love, and providing several brief
      clinical illustrations. The leading edge question guiding my discussion is "How
      does analytic change occur?"

PMID- 19379229
TI  - One case, four theories: finding Matthew.
AB  - In this chapter, clinical material illustrates key theoretical concepts and
      underscores the value of Heinz Kohut's radical approach to psychoanalysis. The
      psychodynamic treatment of "Matthew" spans over a decade and traces the
      therapist's immersion in four clinical modalities. The transition from Kleinian
      and British object relations orientations to a therapeutic style informed by
      psychoanalytic self psychology and intersubjective systems theory broke through
      impasses generated in the earlier chapters of Matthew's therapy. The empathic
      listening stance, the impact of the analyst's subjectivity on the treatment's
      progress, and the vital role of selfobject experiences in the development,
      restoration, and maintenance of an individual's sense of self constitute a few of
      the crucial and enduring curative elements brought to the field of psychoanalysis
      and psychodynamic therapy by Kohut's pioneering efforts.

PMID- 19379230
TI  - The evolution of the psychology of the self: toward a mature narcissism.
AB  - Since the publication of Heinz Kohut's last book in 1984, "self psychology" has
      become much more diverse in its perspectives and even fragmented in its
      applications. Perhaps due in large part to Kohut's own inconsistencies and lack
      of clarity on certain major points of theory and technique, self psychology
      currently lacks a clear definition and has become increasingly marginalized in
      the larger psychoanalytic community, even as some concepts have been absorbed
      into more general psychoanalytic usage. Major theoretical and clinical concepts
      in self psychology remain foggy in their definition and in their clinical
      application. This article will outline an essential paradigm for a psychoanalytic
      self psychology, given the author's background in social science, and its
      connection to particular psychoanalytic values. Focal changes in post-Kohutian
      self psychology that conflict with these views are briefly reviewed; changes that
      I saw at odds with not only the basic orientation of self psychology but also
      with psychoanalysis itself. Changes in the selfobject concept and in how the role
      of early trauma is understood in the context of Kohut's concept of optimal
      frustration are discussed. A clinical illustration demonstrates my concern that
      the introduction of the relational perspective in self psychology appears to
      interfere with psychoanalytic goals per se; that heavy reliance on present
      reality and "optimal gratification" is at the expense of access to the
      unconscious and interferes with achievement of specific analytic goals regarding
      the acquisition of maturity in the narcissistic realm. These conclusions relocate
      self psychology within the fabric of psychoanalysis and its emphasis on the self
      as internal.

PMID- 19379232
TI  - Empathic understanding: the foundation of self-psychological psychoanalysis.
AB  - Empathy is the theoretical and philosophical foundation of self-psychological
      treatment. By emphasizing empathy as the primary methodology for collecting data
      about our patients, Kohut subtly, but dramatically, shifted psychoanalysis from
      Freud's theory-based treatment to a patient-centered treatment in which there is
      a profound shift in the analyst's listening perspective. This chapter explores
      the implications of such a shift in our listening perspective for both
      psychoanalytic treatment and developmental understanding. Using verbatim dialogue
      from both patient-therapist interactions and parent-child interactions, it
      delineates empathy's important role in therapeutic healing as well as its growth
      promoting functions in a child's development.

PMID- 19379231
TI  - Trauma-centered psychoanalysis: transforming experiences of unbearable
      uncertainty.
AB  - By destroying the certainties that pattern psychological life, trauma plunges a
      relational system into chaos and exposes its victims to experiences of unbearable
      uncertainty. When viewed from this perspective, trauma regains its original
      position at the heart of psychoanalysis. To show how this conceptualization grows
      out of and improves upon her earlier writings, the author traces the evolution of
      three ideas that have informed her work for over 20 years: (1) trauma is
      relational, (2) trauma is a complex phenomenon involving both a shattering
      experience and efforts at restoration, and (3) trauma goes hand in hand with
      dissociation. The chapter focuses on ways in which the systemic transformation of
      experiences of existential uncertainty affects posttraumatic life. Special
      attention is paid to reductions of complexity by means of relational patterns
      involving denials of sameness and difference and the emergence of rigid
      dualities. Insofar as analysts are no more strangers to trauma than are their
      patients, these patterns often come to organize treatment. An illustrative
      clinical example describes the treatment of a woman who was severely traumatized
      by incestuous abuse and emotional abandonment in early life. A crisis in the
      analytic relationship arose when the patient's pattern of relating to men revived
      painful memories of trauma in the author's own life. The chapter concludes with a
      discussion of analytic treatment as a "a tyranny of hope" and the bilateral
      nature of healing.

PMID- 19379233
TI  - On ideals and idealization.
AB  - This chapter repositions ideals away from their role as defensive structures
      restraining aggressive and lustful drives (as traditionally viewed) toward their
      place in shaping creativity and love. We select and mold our particular ideals in
      providing meaning and in this manner help to create those selfobjects needed to
      resolve or soothe our needs. This creative process may include "reshaping" of the
      available object to represent the "idealized other." From this perspective,
      Kohut's view of idealization and the idealized parental imago will be considered,
      including my own notion of a one-and-a-half person psychology. Our ideals
      inevitably conflict and clash, leading to internal self-conflicts that generate
      what I call the dialectic of narcissism. Narcissism is here considered broadly,
      reflecting all attributes of self-experience. Shame plays an important role in
      this dialectic, relating to failure with regard to ideals and to falling short of
      cherished goals. Ultimately, it is the shaping of, and approximation to, flexible
      and meaningful ideals that comprise that lofty, ineffable, human ideal--wisdom.
      Clinical vignettes will be offered to illustrate these themes.

PMID- 19379234
TI  - Psychoanalytic self psychology and its conceptual development in light of
      developmental psychology, attachment theory, and neuroscience.
AB  - The chapter starts with a historical overview of the subject of narcissism in
      psychoanalysis. Some sociophilosophical definitions of narcissism are explained
      and the connection to self psychology is described. It is especially referred to
      Honneth's Struggle for Recognition, which is related to the need for selfobject
      experiences. An outline of different concepts concerning narcissism, especially
      in the European psychoanalytic tradition, follows and leads to a clearer
      understanding of Kohut's conception of the self and its selfobjects. Because self
      psychology can often be understood as applied developmental psychology, useful
      links to attachment research are described and the move to the level of
      representation by mentalization is clarified. Further development of self
      psychology in the direction of intersubjectivity helps to supply connections to
      systems theory. Recently developed theories of empathy with reference to
      neurobiological findings provide a dynamic perspective of the activation of
      empathy. Thus, empathy seems to be better understood as a sort of contagion on
      which cognitive cortical processes are superimposed. Finally, the therapeutic
      process in psychoanalytic self psychology is portrayed. This process implies a
      disruption and repair process by which transmuting internalization can take
      place. More current theories of self psychology view this process in its essence
      intersubjectively as a co-construction between patient and analyst. The paper
      concludes with some hints for a paradigm shift in the direction of a more
      holistic understanding of the self.

PMID- 19379235
TI  - From selfobjects to dialogue: a journey through the intersubjective field.
AB  - The intersubjective field concept is a doorway to a dialogical sensibility. A
      dialogical attitude recognizes just how thoroughly and intimately any effort to
      understand another implicates both parties in the dialogue. The therapist's task
      is to engage in a dialogue that stands the greatest chance of enabling the
      therapist to understand how our patients' experiences--and ours--make perfect
      sense at this time in this situation together, even when our patients' statements
      challenge our equilibrium or raise our defenses. In addition, many patients also
      struggle toward an engagement with their analyst not just as a repetitive figure
      (and not even as someone who merely serves their developmental needs). I think
      they strive for a more complex experience of the analyst in his or her
      subjectivity. Our ability to welcome them into our experiential worlds is often
      transformative in restoring a sense of dignity to emotionally alienated patients.
      An extended case example demonstrates these ideas.

PMID- 19379236
TI  - My relational self psychology.
AB  - In this article, I suggest recent sources of influence on psychoanalysis and
      describe a contemporary relational self psychology that is my personal attempt at
      integration. Even with this integration, I struggle to find the right
      "therapeutic" balance between my essential but imperfect instrument for empathic
      listening, on the one hand, and the risks of authentic engagement, on the other.
      These dialectical tensions in me mirror those in the psychoanalytic community as
      a whole, poised between a scientifically based practice and a healing "art"--or
      between a complex but teachable methodology or discipline-and an ordinary (yet
      extraordinary) human relationship in which spontaneity and even improvisation
      play a role. Complicating this balancing act, there is new evidence from
      neuroscientists, attachment theorists, and infant-caregiver researchers that,
      from birth onward, bidirectional influences on brain and psychic development
      create contingent and unpredictable outcomes in every intimately related dyad.
      Thus, the contemporary analyst must expect to be changed by the work and--while
      taking full responsibility for his or her own contribution--must recognize
      patient and analyst as co-creators of the psychoanalytic project. At the same
      time that we now recognize contingency, complexity, and chaos at the heart of
      human minds and relationships, we also acknowledge the central importance of a
      sense of continuity and coherence as the individual undertakes the pursuit of
      goals and relationships in life. What kind of relationship can facilitate these
      qualities in the sense of self? That is the question that this article undertakes
      to answer.

PMID- 19379238
TI  - Embracing the limits of psychoanalysis: a dialogic approach to healing.
AB  - This article outlines my essential paradigm as it relates to self psychology, how
      I arrived at it, and how I would position my perspective in the context of the
      larger psychoanalytic and scientific community. My dialogic complexity systems
      model is most closely aligned with the intersubjective systems theory of Atwood
      and Stolorow and was shown to have acquired its defining shape in the context of
      an in-depth exploration of the connection between the latter theory and Kohut's
      self psychology. My paradigm is part of the wider relational turn in contemporary
      psychoanalysis. I have characterized the evolution of my perspective as my
      continuous preoccupation with the deepening and refinement of my understanding of
      the limits of psychoanalytic theory and practice and the cultivation of a
      clinical attitude that allows me to fully embrace those limits, an attitude that
      combines the caring ambience of genuine dialogue with the spiritual calmness of
      nondual awareness. My perspective can, therefore, be understood as my ongoing
      attempt at unifying my intellect, my heart, and my spirit into one experiential
      whole. A dialogic complexity systems model grounded in a post-Cartesian nondual
      philosophy constitutes the explanatory reduction of my theory and philosophy as
      lived in real time.

PMID- 19379237
TI  - A self-psychological approach to the study of biography: the interplay of
      narratives in psychoanalysis and biography.
AB  - This chapter is an exploration of the psychoanalytic aspects of biography and the
      biographical aspects of psychoanalysis. The narratives that emerge from biography
      and psychoanalytic treatment incorporate elements of empathy, ideology (theory),
      and transference/countertransference and are co-constructed within an
      intersubjective field involving the subjectivities of both participants, the
      biographer and her subject and the analyst and her analysand. I will provide
      examples that demonstrate the way in which these processes play out in the
      biographical realm. Correspondingly, I will illustrate the way in which the
      analyst's biography and analysand's autobiography change in the course of the
      psychoanalytic treatment. Salient differences between biographical and
      psychoanalytic endeavors are also discussed.

PMID- 19379239
TI  - Art and self: a new psychoanalytic perspective on creativity and aesthetic
      experience.
AB  - The following article presents a contemporary self-psychological perspective on
      aesthetic experience, art, and creativity. The author argues that aesthetics is
      as important to human life as sex, hunger, aggression, love, and hate. Although
      we may rarely be conscious of it, aesthetic experience gives form, meaning, and,
      most importantly, value to everything we are, all we experience, and everything
      we do. Theoretically without it, life would be a shapeless, meaningless, and
      colorless series of sensations, events, and reactions. Aesthetic experience
      achieves its most refined form in the fine arts. However, we can also see its
      most archaic manifestation in the curve of the mother's shoulder during nursing,
      her heartbeat and breath, the melody of her voice, the balance of her eyes and
      smile--all embedded in the warmth, nourishment, and security of the mother-infant
      interaction. This article reviews recent analytic writings on psychoanalytic
      aesthetics that emphasize the central role of early childhood relational
      experiences in the emergence and structuralization of the sense of aesthetic
      form. The author argues that as a result of developmentally based processes of
      idealization, the child's aesthetic sense takes on a profound and lifelong
      concern with form and quality. The author extends this model and proposes a new
      definition of creativity and the nature of art. He argues that the creative
      artist is concerned not just with articulation of subjective states of feeling
      but also with the most refined and perfect expression possible of his or her
      internal vision. Although a major application of this model is to art and
      creativity, it is argued that aesthetic experience is a pervasive human trait
      that impacts on our entire experience of life, self, and relationships.

PMID- 19379240
TI  - Selfobject as dramatis personae: cultivating the improvisational in self
      psychological psychoanalysis.
AB  - This chapter discusses the influence of drama in the author's background in
      conceptualizing psychoanalytic theory and practice. The history of ideas relevant
      to a dramaturgical analysis from Freud to Kohut's revolution, with additional
      modifications by relational psychoanalysis, is explored. The author poses a
      trimodal model of a dramatrugically informed improvisational play in
      psychoanalytic treatment, with an accompanying case illustration.

PMID- 19379241
TI  - Relational trauma and the developing right brain: an interface of psychoanalytic
      self psychology and neuroscience.
AB  - Psychoanalysis, the science of unconscious processes, has recently undergone a
      significant transformation. Self psychology, derived from the work of Heinz
      Kohut, represents perhaps the most important revision of Freud's theory as it has
      shifted its basic core concepts from an intrapsychic to a relational unconscious
      and from a cognitive ego to an emotion-processing self. As a result of a common
      interest in the essential, rapid, bodily based, affective processes that lie
      beneath conscious awareness, a productive dialogue is now occurring between
      psychoanalysis and neuroscience. Here I apply this interdisciplinary perspective
      to a deeper understanding of the nonconscious brain/mind/body mechanisms that lie
      at the core of self psychology. I offer a neuropsychoanalytic conception of the
      development and structuralization of the self, focusing on the experience
      dependent maturation of the emotion-processing right brain in infancy. I then
      articulate an interdisciplinary model of attachment trauma and pathological
      dissociation, an early forming defense against overwhelming affect that is a
      cardinal feature of self-psychopathologies. I end with some thoughts on the
      mechanism of the psychotherapeutic change process and suggest that self
      psychology is, in essence, a psychology of the unique functions of the right
      brain and that a rapprochement between psychoanalysis and neuroscience is now at
      hand.

PMID- 19379242
TI  - The interface of self psychology, infant research, and neuroscience in clinical
      practice.
AB  - This article focuses on the integration of self psychology with findings from
      infant research and neuroscience. While Kohut's psychology of the self provides a
      useful theoretical model for psychoanalytic practice, aspects of infant research
      and neuroscience offer specificity and nuance to basic self-psychological
      concepts. Kohut proposed that self-psychological psychoanalysis ameliorates
      derailed development through patient-analyst interaction, while a listening
      stance of empathic immersion begins the curative process of derailed development
      and sets the stage for reparative psychoanalytic work. Findings from infant
      research delineate much more specifically the nature of attunement both in early
      mother-infant and analyst-patient interactions. Findings from neuroscientific
      research delineate how early mother-infant experiences are encoded in implicit
      memory and explicates the emotional substrate of affects and feelings. This
      emotional substrate exists at birth and provides a means of communication both in
      infancy and adulthood. Additionally, infant research delineates the mutuality of
      the interactive process. Thus, both infant research and neuroscience add subtlety
      and nuance to basic self-psychological concepts. This subtlety opens up new ways
      of understanding patients and expands the clinical repertoire. Three clinical
      vignettes demonstrate how this nuance and expansion of self-psychological
      concepts are applied in the context of an ongoing psychoanalytic treatment.

PMID- 19379243
TI  - Self psychology and the modern dance choreographer.
AB  - Theory and research methodology of self psychology are integrated with the
      experiences of modern dance choreographers to investigate the importance of
      creativity, art making, and aesthetics in mental health and our everyday lives.
      Empathy, as aesthetically based, is explored to understand the capacity of the
      arts to unite us in our humanity. Connections between aesthetic development,
      creativity, and infant patterns of learning are drawn. The influence of sensual
      and exploration/assertion motivational systems upon the contemporary
      choreographer are highlighted, leading to an understanding of the selfobject
      function of sensation and movement for the dance artist. Through an examination
      of the moment to moment ritualized experiences of studio work, the creative
      process in making dances is discussed. Ultimately understanding creativity and
      aesthetically based empathy inform our delineation of mental health and the need
      for aesthetic experience in everyday life.

PMID- 19379244
TI  - My life with self psychology.
AB  - In this very personal writing, I describe my experiences with self psychology in
      general and with Heinz Kohut in particular, from its beginnings in the early
      1970s until Kohut's death and my own subsequent development. The discovery of
      self psychology in the context of my beginnings as a new, rather disillusioned,
      candidate in a classical institute affiliated with the American Psychoanalytic
      Association is described, with the sense of relief that comes with finding a
      theoretical perspective that matched my own views about human beings. My
      experiences as a member of the small study group that met in Chicago under the
      leadership of Kohut, what that was like for me, and how I came to both grow under
      his influence and then to find my own voice from within that influence forms the
      majority of this essay of deep appreciation for Kohut the man and Kohut the
      founder of a psychoanalytic theory.

PMID- 19379245
TI  - Intersubjective systems theory: a fallibilist's journey.
AB  - Intersubjective systems theory is the view that personal experience always
      emerges, maintains itself, and transforms in relational contexts. It is held for
      reasons of personal inclinations, philosophical belief, and clinical conviction.
      As a clinical sensibility, it primarily includes an emphasis on the emotional
      convictions or organizing principles that systematize experience, the personal
      engagement of the analyst, and the refusal to argue about reality.

PMID- 19379246
TI  - The road to my (self) psychology.
AB  - This chapter describes how I developed my self-psychological perspective. It
      provides the reader with a short summary of my personal history--how I grew up in
      New York City and now live and work as a psychoanalyst in Munich, Germany.
      Included is a description of important mentors in my life who have provided me
      with invaluable support. At the end of the chapter there are two cases presented.
      The first describes the case of Mrs. A. She entered analysis with a great
      difficulty in her ability to speak (i.e., a deficit in her narrative self). The
      second case of Mr. B provides the reader with two complete analytic sessions. I
      do not comment on the content and intent of my interventions or interpretations
      but leave it open to the readers to develop their own thoughts, and, if they
      like, they can send me personal feedback to my e-mail address.

PMID- 19379247
TI  - From self psychology to selves in relationship: a radical process of micro and
      macro expansion in conceptual experience.
AB  - This article traces four shifts in conceptualization marking the
      theoretical/clinical journey of this author's developmental movement from a self
      psychologist to a selves-in-relationship psychoanalyst. It commences with a
      recognition that the analyst's conceptualizations, building blocks of organizing
      activity, are actions that impact self and other. Psychoanalysis was initiated as
      a practice in open-systems thinking, the hallmark of scientific observation and
      meaning making. Continuing in this tradition requires careful attention to
      clinical experiences anomalous to what a particular conceptualization might lead
      one to expect or to how that conceptualization might inform one's response. Such
      anomalous experiences, as Kohut demonstrated, can require expansion or emendation
      in conceptualization as central to the analyst's clinical activity. Four key
      concepts emerging in the self-psychological tradition are revisited for
      conceptual expansion: mirroring, self, attunement, and rupture repair. Each
      reformulation impacts on and is constituted, in part, by the other, hence the
      nonlinear relationship between these concepts. Each reformulation is grounded in
      a clinical illustration and marks a shift from structural conceptualization to
      process conceptualization characterized by attention to, and narration of, the
      analyst's as well as the analysand's subjective experience and contribution to
      the clinical interaction. Furthermore, clinical attention is expanded to the
      micro dimensions of nonsymbolic-embodied experiences and the macro dimensions of
      how different cultural beliefs and customs, shaped by both local as well as
      professional identifications, can influence the meaning-making process of the
      analyst's subjective organizations of self, other, and intersubjective processes.
      In the clinical illustrations narrated, these reconceptualizations are
      demonstrated to have significant impact on how analyst and analysand interact.

PMID- 19379248
TI  - How self psychology found me.
AB  - The author describes the evolution of self psychology from Kohut's early work to
      the present through the lens of her own life and work.

PMID- 19379249
TI  - Theory is personal.
AB  - In "Theory Is Personal," Allen Siegel MD, a Chicago psychoanalyst and Assistant
      Professor of Clinical Psychiatry at Rush University Medical Center, shares the
      very personal story of how he came to his theory. Sometimes we find our theory.
      Other times, Siegel argues, it is our theory that finds us. In this article
      Siegel catalogues his early encounters with figures--contemporary and real--from
      Sigmund Freud to influential department chairs to an analyst who would become
      legendary for introducing a bold new theory into the psychoanalytic canon.
      Charting key experiences that shaped his adoption of this new approach--a
      depression in response to his first patient, a clinical treatment with Heinz
      Kohut, and exposure to others who dared to challenge Freud--Siegel describes the
      theory that brought both himself and his patients to life. After outlining the
      principles that guide the new theory and practice known as self psychology,
      Siegel tells of the empathic ambiance that can now emerge in the consulting room.
      Finally, he shows how this new theory of human motivation provides not merely a
      rationale for psychotherapy but an explanatory apparatus for understanding human
      action in the world beyond the consulting room. He turns to a brief study of
      aggression and war, as expressed in a 1932 correspondence between Albert Einstein
      and Sigmund Freud, to illustrate how the understanding of aggression and war
      changes significantly when empathy is the field's data collecting instrument.

PMID- 19379250
TI  - Peeling the onion: understanding layers of treatment.
AB  - How can a psychoanalyst account for and recount the process of understanding the
      therapeutic endeavor? What happens in those moments, co-created by patient and
      analyst, when the consultation room comes "alive" in ways that defy easy or
      simplistic answers? How does an analyst come to understand psychoanalytic
      treatment as a bidirectional, dyadic, dynamic, interactively regulated
      relationship? Understanding the psychoanalytic treatment process from a
      disciplined, yet spontaneous, nonlinear perspective is the focus of this chapter.
      The overarching treatment process will be considered through the presentation of
      vignette of a treatment with a school-aged child.

PMID- 19379251
TI  - The journey of a psychoanalyst.
AB  - This chapter discusses the author's involvement with contemporary self
      psychology. Beginning from a traditional Freudian background, the author's
      history is traced to her current psychoanalytic interest in applying infant
      research to adult treatment. A case example is provided illustrating the
      interweaving of the verbal/explicit and nonverbal/implicit dimensions of working
      with a patient traumatized following the World Trade Center disaster.

PMID- 19379261
TI  - Treatment for Leigh syndrome by monitoring dichloroacetate concentration.

PMID- 19379262
TI  - Hyperkalemia in a neonate with congenital myotonic dystrophy.

PMID- 19379263
TI  - Dizygotic twins with neonatal alloimmune neutropenia associated with maternal
      anti-human neutrophil antigen-1B antibody.

PMID- 19379264
TI  - Role of varicella virus and anticardiolipin antibodies in the development of
      stroke in a patient with Down syndrome associated with Moyamoya syndrome.

PMID- 19379265
TI  - Functional and anatomic correlation of splenic regeneration following
      embolization.

PMID- 19379266
TI  - Hyperammonemia and positive allopurinol test in hyperinsulinism-hyperammonemia
      syndrome: Taiwanese case report.

PMID- 19379267
TI  - Intrapleural streptokinase treatment for postoperative coagulated hemothorax in a
      newborn.

PMID- 19379268
TI  - Interleukin-12/-23 receptor beta 1 deficiency in an infant with draining BCG
      lymphadenitis.

PMID- 19379269
TI  - Asthma and lung function at school age after bronchiolitis in infancy.

PMID- 19379270
TI  - Mean platelet volume in neonatal respiratory distress syndrome.
AB  - The aim of this study was to investigate the differences in mean platelet volume
      (MPV) between neonates with and without neonatal respiratory distress syndrome
      (RDS). Eighty-three premature infants who were admitted to the neonatal intensive
      care unit were included in the study. Forty-four of these infants were diagnosed
      as having RDS and the other 39 infants were non-RDS patients. Infants born to
      mothers with pre-eclampsia, or a drug history that had negative effects on
      platelet count, perinatal hypoxia, sepsis and necrotizing enterocolitis were
      excluded. Blood collection was done on the first and third days of life. There
      were no demographic, gestational or platelet count differences between groups,
      but MPV was higher in RDS patients and this difference was statistically
      significant (P= 0.011). High platelet volumes in RDS patients is probably related
      to young platelet production and may be a result of increased platelet
      consumption in pulmonary damage due to RDS.

PMID- 19379273
TI  - Fate map of the chick embryo neural tube.
AB  - Fate-map studies have provided important information in relation to the regional
      topology of brain areas in different vertebrate species. Moreover, these studies
      have demonstrated that the distribution of presumptive territories in neural
      plate and neural tube are highly conserved in vertebrates. The aim of this review
      is to re-examine and correlate the distribution of presumptive neuroepithelial
      domains in the chick neural tube with molecular information and discuss recent
      data. First, we review descriptive fate map studies of neural plate in different
      vertebrate species that have been studied using diverse fate-mapping methods.
      Then, we summarize the available data on the localization of neuroepithelial
      progenitors for the brain subregions in the chick neural tube at stage HH10-11,
      the most used stage for experimental embryology. This analysis is mainly focused
      on experimental fate mapping results using quail-chick chimeras.

PMID- 19379274
TI  - Cnidarians and the evolutionary origin of the nervous system.
AB  - Cnidarians are widely regarded as one of the first organisms in animal evolution
      possessing a nervous system. Conventional histological and electrophysiological
      studies have revealed a considerable degree of complexity of the cnidarian
      nervous system. Thanks to expressed sequence tags and genome projects and the
      availability of functional assay systems in cnidarians, this simple nervous
      system is now genetically accessible and becomes particularly valuable for
      understanding the origin and evolution of the genetic control mechanisms
      underlying its development. In the present review, the anatomical and
      physiological features of the cnidarian nervous system and the interesting
      parallels in neurodevelopmental mechanisms between Cnidaria and Bilateria are
      discussed.

PMID- 19379275
TI  - Evolution and regeneration of the planarian central nervous system.
AB  - More than 100 years ago, early workers realized that planarians offer an
      excellent system for regeneration studies. Another unique aspect of planarians is
      that they occupy an interesting phylogenetic position with respect to the nervous
      system in that they possess an evolutionarily primitive brain structure and can
      regenerate a functional brain from almost any tiny body fragment. Recent
      molecular studies have revisited planarian regeneration and revealed key
      information about the cellular and molecular mechanisms underlying brain
      regeneration in planarians. One of our great advances was identification of a
      gene, nou-darake, which directs the formation of a proper extrinsic environment
      for pluripotent stem cells to differentiate into brain cells in the planarian
      Dugesia japonica. Our recent findings have provided mechanistic insights into
      stem cell biology and also evolutionary biology.

PMID- 19379276
TI  - Cell type and function of neurons in the ascidian nervous system.
AB  - Ascidians, or sea squirts, are primitive chordates, and their tadpole larvae
      share a basic body plan with vertebrates, including a notochord and a dorsal
      tubular central nervous system (CNS). The CNS of the ascidian larva is formed
      through a process similar to vertebrate neurulation, while the ascidian CNS is
      remarkably simple, consisting of about 100 neurons. Recent identification of
      genes that are specifically expressed in a particular subtype of neurons has
      enabled us to reveal neuronal networks at single-cell resolution. Based on the
      information on neuron subtype-specific genes, different populations of neurons
      have been visualized by whole-mount in situ hybridization, immunohistochemical
      staining using specific antibodies, and fluorescence labeling of cell bodies and
      neurites by a fluorescence protein reporter driven by neuron-specific promoters.
      Neuronal populations that have been successfully visualized include
      glutamatergic, cholinergic, gamma-aminobutyric acid/glycinergic, and dopaminergic
      neurons, which have allowed us to propose functional regionalization of the CNS
      and a neural circuit for locomotion. Thus, the simple nervous system of the
      ascidian larva can serve as an attractive model system for studying the
      development, function, and evolution of the chordate nervous system.

PMID- 19379277
TI  - Basal process and cell divisions of neural progenitors in the developing brain.
AB  - The basal process is an extension of certain types of neural progenitors during
      brain development; that is, the neuroepithelial and radial glial cells, which
      show radial orientation, emanating from their cell body. Originally, the basal
      process was considered to serve as a scaffold for the migration of newborn
      neurons, but recent observations obtained by advanced genetic manipulations and
      microscopic methods show that the basal process has additional roles. In this
      review, we first summarize the role of the radial glial basal process for
      neuronal migration and signaling and for the proper organization of the
      developing brain. We then focus on the emerging roles of the basal process during
      the division of neural progenitor cells, specifically the various modes of
      division of neuroepithelial and radial glial cells.

PMID- 19379278
TI  - Developmental anatomy of reeler mutant mouse.
AB  - The reeler mouse is one of the most famous spontaneously occurring mutants in the
      research field of neuroscience, and this mutant has been used as a model animal
      to understand mammalian brain development. The classical observations emphasized
      that laminar structures of the reeler brain are highly disrupted. Molecular
      cloning of Reelin, the gene responsible for reeler mutant provided insights into
      biochemistry of Reelin signal, and some models had been proposed to explain the
      function of Reelin signal in brain development. However, recent reports of reeler
      found that non-laminated structures in the central nervous system are also
      affected by the mutation, making function of Reelin signal more controversial. In
      this review, we summarized reported morphological and histological abnormalities
      throughout the central nervous system of the reeler comparing to those of the
      normal mouse. Based on this overview of the reeler abnormalities, we discuss
      possible function of Reelin signal in the neuronal migration and other
      morphological events in mouse development.

PMID- 19379279
TI  - Fibroblast growth factor signaling in development of the cerebral cortex.
AB  - Despite substantial and exciting recent progress in our understanding of
      developmental processes in the cerebral cortex, there is still much to be learned
      about the molecular and cellular mechanisms that account for formation of the
      cortical structures, and in turn, how the regulation of these mechanisms is
      linked to cortical functions and behaviors in animals and humans. Fibroblast
      growth factors (FGFs) are a classic family of growth factors that are important
      in neural development and whose structures and signaling have been well-studied
      molecularly and biochemically. Recent advances have revealed their diverse but
      specific functions in patterning and neurogenesis during cortical development, as
      evidenced by multiple experimental approaches using in vivo models. Importantly,
      changes in FGF signaling during development have been shown to influence
      structure and function of the cerebral cortex as well as animal behavior, and
      have been implicated in disorders of nervous system function and intellectual
      development in humans. For example, disturbance of FGF pathways during
      development has been implicated in the pathogenesis of autism spectrum disorders.
      Experimental models with altered cortical structure due to perturbations of FGF
      signaling present a unique opportunity whereby molecular and cellular mechanisms
      that underlie cortical function and animal behavior can be directly studied and
      linked to each other.

PMID- 19379282
TI  - Marathon of eponyms: 2 Bell palsy (idiopathic facial palsy).
AB  - The use of eponyms has long been contentious, but many remain in common use, as
      discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185-186). The use of
      eponyms in diseases of the head and neck is found mainly in specialties dealing
      with medically compromised individuals (paediatric dentistry, special care
      dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology,
      oral and maxillofacial radiology and oral and maxillofacial surgery) and
      particularly by hospital-centred practitioners. This series has selected some of
      the more recognised relevant eponymous conditions and presents them
      alphabetically. The information is based largely on data available from MEDLINE
      and a number of internet websites as noted below: the authors would welcome any
      corrections. This document summarises data about Bell paralysis.

PMID- 19379283
TI  - New tools for single nucleotide polymorphism (SNP) discovery and analysis
      accelerating plant biotechnology.

PMID- 19379284
TI  - A high-throughput assay for rapid and simultaneous analysis of perfect markers
      for important quality and agronomic traits in rice using multiplexed MALDI-TOF
      mass spectrometry.
AB  - The application of single nucleotide polymorphisms (SNPs) in plant breeding
      involves the analysis of a large number of samples, and therefore requires rapid,
      inexpensive and highly automated multiplex methods to genotype the sequence
      variants. We have optimized a high-throughput multiplexed SNP assay for eight
      polymorphisms which explain two agronomic and three grain quality traits in rice.
      Gene fragments coding for the agronomic traits plant height (semi-dwarf, sd-1)
      and blast disease resistance (Pi-ta) and the quality traits amylose content
      (waxy), gelatinization temperature (alk) and fragrance (fgr) were amplified in a
      multiplex polymerase chain reaction. A single base extension reaction carried out
      at the polymorphism responsible for each of these phenotypes within these genes
      generated extension products which were quantified by a matrix-assisted laser
      desorption ionization-time of flight system. The assay detects both SNPs and
      indels and is co-dominant, simultaneously detecting both homozygous and
      heterozygous samples in a multiplex system. This assay analyses eight functional
      polymorphisms in one 5 microL reaction, demonstrating the high-throughput and
      cost-effective capability of this system. At this conservative level of
      multiplexing, 3072 assays can be performed in a single 384-well microtitre plate,
      allowing the rapid production of valuable information for selection in rice
      breeding.

PMID- 19379285
TI  - High-throughput single nucleotide polymorphism genotyping in wheat (Triticum
      spp.).
AB  - Over the past few years, considerable progress has been made in high-throughput
      single nucleotide polymorphism (SNP) genotyping technologies, largely through the
      investment of the human genetics community. These technologies are well adapted
      to diploid species. For plant breeding purposes, it is important to determine
      whether these genotyping methods are adapted to polyploidy, as most major crops
      are former or recent polyploids. To address this problem, we tested the capacity
      of the multiplex technology SNPlex with a set of 47 wheat SNPs to genotype DNAs
      of 1314 lines that were organized in four 384-well plates. These lines
      represented different taxa of tetra- and hexaploid Triticum species and their
      wild diploid relatives. We observed 40 markers which gave less than 20% missing
      data. Different methods, based on either Sanger sequencing or the MassARRAY
      genotyping technology, were then used to validate the genotypes obtained by
      SNPlex for 11 markers. The concordance of the genotypes obtained by SNPlex with
      the results obtained by the different validation methods was 96%, except for one
      discarded marker. Furthermore, a mapping study on six markers showed the expected
      genetic positions previously described. To conclude, this study showed that high
      throughput genotyping technologies developed for diploid species can be used
      successfully in polyploids, although there is a need for manual reading. For the
      first time in wheat species, a core of 39 SNPs is available that can serve as the
      basis for the development of a complete SNPlex set of 48 markers.

PMID- 19379286
TI  - Multiplex single nucleotide polymorphism (SNP)-based genotyping in allohexaploid
      wheat using padlock probes.
AB  - Single nucleotide polymorphisms are the most common polymorphism in plant and
      animal genomes and, as such, are the logical choice for marker-assisted
      selection. However, many plants are also polyploid, and marker-assisted selection
      can be complicated by the presence of highly similar, but non-allelic,
      homoeologous sequences. Despite this, there is practical and academic demand for
      high-throughput genotyping in several polyploid crop species, such as
      allohexaploid wheat. In this paper, we present such a system, which utilizes
      public single nucleotide polymorphisms previously identified in both
      agronomically important genes and in randomly selected, mapped, expressed
      sequence tags developed by the wheat community. To achieve relatively high levels
      of multiplexing, we used non-amplified genomic DNA and padlock probe pairs,
      together with high annealing temperatures, to differentiate between similar
      sequences in the wheat genome. Our results suggest that padlock probes are
      capable of discriminating between homoeologous sequences and hence can be used to
      efficiently genotype wheat varieties.

PMID- 19379287
TI  - Preventing cerebral palsy: hidden improvements.

PMID- 19379288
TI  - Walking function, pain, and fatigue in adults with cerebral palsy.

PMID- 19379289
TI  - Exogenous melatonin for sleep problems in individuals with intellectual
      disability: a meta-analysis.
AB  - Recent meta-analyses on melatonin has raised doubts as to whether melatonin is
      effective in treating sleep problems in people without intellectual disabilities.
      This is in contrast to results of several trials on melatonin in treating sleep
      problems in individuals with intellectual disabilities. To investigate the
      efficacy of melatonin in treating sleep problems in individuals with intellectual
      disabilities, we performed a meta-analysis of placebo-controlled randomized
      trials of melatonin in individuals with intellectual disabilities and sleep
      problems. Data were selected from articles published on PubMed, Medline, and
      Embase between January 1990 and July 2008. We examined the influence of melatonin
      on sleep latency, total sleep time, and number of wakes per night. Quality of
      trials was assessed using the Downs and Black checklist. Nine studies (including
      a total of 183 individuals with intellectual disabilities) showed that melatonin
      treatment decreased sleep latency by a mean of 34 minutes (p<0.001), increased
      total sleep time by a mean of 50 minutes (p<0.001), and significantly decreased
      the number of wakes per night (p<0.05). Melatonin decreases sleep latency and
      number of wakes per night, and increases total sleep time in individuals with
      intellectual disabilities.

PMID- 19379290
TI  - Airway clearance in neuromuscular weakness.
AB  - Impaired airway clearance leads to recurrent chest infections and respiratory
      deterioration in neuromuscular weakness. It is frequently the cause of death.
      Cough is the major mechanism of airway clearance. Cough has several components,
      and assessment tools are available to measure the different components of cough.
      These include measuring peak cough flow, respiratory muscle strength, and
      inspiratory capacity. Each is useful in assessing the ability to generate an
      effective cough, and can be used to guide when techniques of assisting airway
      clearance may be effective for the individual and which are most effective.
      Techniques to assist airway clearance include augmenting inspiration by air
      stacking, augmenting expiration by assisting the cough, and augmenting both
      inspiration and expiration with the mechanical insufflator-exsufflator or by
      direct suctioning via a tracheostomy. Physiotherapists are invaluable in
      assisting airway clearance, and in teaching patients and their families how to
      use these techniques. Use of the mechanical insufflator-exsufflator has gained
      popularity in recent times, but several simpler, more economical methods are
      available to assist airway clearance that can be used effectively alone or in
      combination. This review examines the literature available on the assessment and
      management of impaired airway clearance in neuromuscular weakness.

PMID- 19379291
TI  - Spectrum of epilepsy and electroencephalogram patterns in Wolf-Hirschhorn
      syndrome: experience with 87 patients.
AB  - To define the spectrum of epilepsy in Wolf-Hirschhorn syndrome (WHS) better, we
      studied 87 patients (54 females, 33 males; median age 5.6 years; age range 1-25.6
      years) with confirmed 4p16.3 deletion. On the basis of clinical charts, we
      retrospectively analyzed the evolution of the electroencephalogram (EEG) findings
      and seizures. Epilepsy occurred in 81 patients (93%) within the first 3 years of
      life. Sixty out of 81 (74%) had generalized tonic-clonic seizures, which was the
      only seizure pattern in 32. Tonic spasms occurred in 15 out of 81 (18%), complex
      partial seizures in 10 out of 81 (12%), and clonic seizures in 6 out of 81 (7%).
      Seizures were frequently triggered by fever (59 out of 81; 73%), and occurred in
      clusters in 36 out of 72 (50%). In the same 36 (50%), unilateral or generalized
      clonic or tonic-clonic status epilepticus occurred during the first 3 years of
      life. Twenty-seven out of 81 patients (33%) developed atypical absences between 1
      and 6 years, accompanied by a myoclonic component involving the eyelids and the
      hands. Distinctive EEG abnormalities were observed in 73 out of 81 (90%).
      Epilepsy was well controlled in 65 out of 81 (81%), mainly with valproate and
      phenobarbital, and improved with age in all. Thirty-two out of 58 (55%) are
      currently seizure-free. Seizures stopped at a median age of 4 years 6 months.
      Epilepsy represents a major clinical challenge in WHS; however, it has a good
      prognosis. Early diagnosis and treatment of atypical absences, subtle and often
      misdiagnosed, is mandatory.

PMID- 19379292
TI  - Kinase inhibitors in cancer therapy.
AB  - Over the past few years, protein kinases have arisen as promising targets for
      therapeutic intervention in cancer therapy. This is due to a combination of
      several key events, including the identification of common kinase dysfunction in
      particular tumours and the recent success of such targeted kinase inhibitors as
      Gleevec (imatinib mesylate) and Iressa (Gefatinib). Ultimately, the success of
      this novel approach will be dependent on the careful identification and
      characterization of protein kinase dysregulation in particular forms of cancer.
      This review focuses on the function of protein kinases in normal cells, the
      mechanisms through which these kinases contribute to tumorigenesis, and the
      development and application of agents designed to inhibit dysfunctional kinases.

PMID- 19379293
TI  - Veterinary Co-operative Oncology Group.

PMID- 19379294
TI  - Veterinary Co-operative Oncology Group - Common Terminology Criteria for Adverse
      Events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy
      in dogs and cats v1.0.

PMID- 19379295
TI  - Evaluation of telomerase-targeted therapies in canine cancer cell lines.
AB  - Despite advances in conventional therapeutics, cancer remains an invariably fatal
      disease, the major challenge being to develop tumour-specific cancer treatment
      strategies. Current treatments such as chemotherapy and radiotherapy rely on a
      crude distinction between cancer cells and normal cells. However, with an
      increased understanding of the molecular events in the development of cancer, it
      is possible that far more innovative and targeted approaches can be developed.
      From studies on humans and dogs, the enzyme telomerase has emerged as a central
      unifying mechanism underlying the immortal phenotype of cancer and has thus
      become a candidate for differentiating between normal and cancer cells. The level
      and frequency of telomerase activity and component gene expression in cancers
      reinforces this as a potential target for cancer therapies. This article
      describes two approaches to target cancer by capitalizing on the expression of
      this enzyme. In the first approach, we target the enzyme itself, the goal being
      to cause cancer cell death. In the second approach, we utilize the respective
      gene promoters for telomerase component enzymes to drive expression of a reporter
      gene in cancer cell lines. The results demonstrated that targeted gene expression
      using promoter elements can be achieved specifically in telomerase-positive cell
      lines. However, targeting the enzyme itself proved less successful and warrants
      investigations into alternative approaches.

PMID- 19379296
TI  - Expression and regulation of cyclooxygenase-2 in normal and neoplastic canine
      keratinocytes.
AB  - Squamous cell carcinoma (SCC) is one of the most common cancers in dogs, yet
      relatively little is known about the molecular events involved in its
      development. Increasing evidence implicates cyclooxygenase-2 (COX-2) in the
      pathogenesis of various cancers in humans and animals. COX-2 overexpression has
      recently been demonstrated in canine SCCs. The objective of our study was to
      characterize the expression and regulation of COX-2 in normal and neoplastic
      canine keratinocytes (CKs) to provide an in vitro system to investigate the
      implication of COX-2 in SCC oncogenesis in dogs. Cell lines derived from normal
      CKs and neoplastic CKs (SCCs) were cultured in the absence or presence of
      agonists, and immunoblots, immunocytochemistry, radioimmunoassays and a cell
      proliferation assay were used to characterize COX-2 expression and action.
      Results showed that neoplastic keratinocytes had a higher basal COX-2 expression
      than normal keratinocytes. In both cell lines, stimulation with the tumour
      promoter phorbol 12-myristate 13-acetate induced a time-dependent increase in COX
      2 protein, with COX-2 induction being stronger in cancerous SCC than in normal CK
      cells. Moreover, SCC cells produced significantly more PGE(2) than CK cells,
      under both baseline and stimulated conditions (P < 0.05). NS-398, a selective COX
      2 inhibitor, inhibited prostaglandin (PG)E(2) synthesis and decreased
      proliferation of CK and SCC cells (P < 0.05). Collectively, our results indicate
      that the canine neoplastic keratinocyte SCC cell line expresses more COX-2 and
      produces more PGE(2) than the normal keratinocyte CK cell line, thus providing an
      in vitro system to study the molecular basis of elevated COX-2 expression in SCCs
      in dogs.

PMID- 19379297
TI  - Middle ear tumours with brainstem extension treated by ventral bulla osteotomy
      and craniectomy in two cats.
AB  - Two geriatric domestic shorthaired cats (DSH) were treated surgically with a
      ventral bulla osteotomy and craniectomy for middle ear tumours that invaded the
      calvarium. Both cats had a history of vestibular disease. One cat had a normal
      neurological examination. Both cats underwent computed tomographic imaging of the
      head. After intravenous injection of an iodinated contrast material, one cat had
      a ring-enhancing intracranial lesion and the other had a uniform contrast
      enhancing intracranial lesion, which either communicated with the bulla or was
      associated with bulla osseous lysis/production. One cat had a papillary adenoma
      and the other had an adenocarcinoma. Both cats had prolonged survivals (630 days;
      alive and lost to follow-up at 840 days), which is longer than reported in cats
      with middle ear neoplasia. Craniectomy, in addition to ventral bulla osteotomy,
      may be part of the treatment plan for middle ear tumours that invade the
      calvarium.

PMID- 19379298
TI  - Treatment of canine haemangiosarcoma with suberoylanilide hydroxamic acid, a
      histone deacetylase inhibitor.
AB  - A case report is presented by describing the treatment of a 12-year-old dog -
      diagnosed with haemangiosarcoma (HSA) - with suberoylanilide hydroxamic acid
      (SAHA), a histone deacetylase (HDAC) inhibitor. The drug was administered orally,
      on a daily basis, approximately 2 weeks post-splenectomy at a dose of 3 mg kg(
      1). HSA is a lethal malignancy of the endothelium, which is usually disseminated
      by the time it is diagnosed. Median survival time, usually, is no longer than 80
      days. Following treatment with SAHA, no sign of malignant growth could be
      discerned by means of diagnostic abdominal ultrasound, chest X-ray or with the
      help of clinical symptoms, over a period of >1000 days. The precise mechanism by
      which HDAC inhibitors exert their anti-cancer effects is uncertain, but evidence
      suggests that exposure to SAHA generates hyperacetylated chromosomal histones,
      which, in turn, facilitates the expression of tumour suppressor genes turned off
      by epigenetic mechanisms during neoplastic transformation of the endothelium.

PMID- 19379299
TI  - Characterization of spindle cell component of ferret (Mustela putorius furo)
      adrenal cortical neoplasms - correlation to clinical parameters and prognosis.
AB  - Adrenal cortical epithelial tumours are common in ferrets. A variant tumour type
      with prominent spindle cell proliferation has been identified. We characterized
      these variant tumours with light microscopy and immunohistochemical analysis and
      correlate these features to clinical parameters and prognosis. We classified 24
      ferret adrenal cortical masses with recognizable spindle cell proliferation
      obtained from the AMC and AFIP databases, based on percentage of spindle cells
      present and features of malignancy. These masses were separated into hyperplastic
      nodules and adenomas (both with 1-24% spindle cells), 'mixed' adenomas (>or=25%
      spindle cells), adenocarcinomas (1-24%) and 'mixed' adenocarcinomas (>or=25%
      spindle cells). Tumours were evaluated immunohistochemically for smooth muscle
      actin (SMA) and estrogen receptor (ER) expression. Disease-free interval (DFI)
      and survival time (ST) were calculated using Kaplan-Meier product limit method.
      Of 24 cases of spindle cell variant adrenal tumours, one was a hyperplastic
      nodule, 10 were adenomas, three were 'mixed' adenomas, six were adenocarcinomas
      and four were 'mixed' adenocarcinomas. The proliferative spindle cell cytoplasm
      was SMA-positive (smooth muscle myocyte origin). ER positivity, seen in nine of
      24 cases, was restricted to adenocarcinomas, 'mixed' adenomas and 'mixed'
      adenocarcinomas. DFI and ST were significantly reduced in 'mixed' adenocarcinomas
      or tumours with ER expression. DFI was significantly reduced in tumours with
      marked smooth muscle. The spindle cell component of these variant adrenal tumours
      is smooth muscle in origin. The presence of abundant smooth muscle, a more
      malignant histologic grade ('mixed' adenocarcinomas) and ER expression are
      significantly positively correlated to both decreased DFI and decreased ST.

PMID- 19379300
TI  - A preliminary assessment of whole-body radiotherapy interposed within a
      chemotherapy protocol for canine lymphoma.
AB  - Six dogs with spontaneously occurring, previously untreated lymphoma were treated
      with half-body radiation therapy (RT) doses interposed in a CHOP-based 25-week
      chemotherapy regimen. Chemotherapy-related toxicities were as expected and were
      mildly increased in severity post-RT compared with pre-RT. Treatment was delayed
      by 1-2 weeks per delay in four dogs due to chemotherapy-related neutropenia.
      Radiation therapy was administered in two consecutive day fractions of 4 Gray to
      the cranial and caudal halves of the body 4 weeks apart. Radiation-related
      toxicities consisted of lethargy, alopecia, diarrhoea of less than 2-day duration
      and average decreases in neutrophil counts of 50%. Late effects from RT were not
      evident. Median remission and survival times for the six dogs were 455 and 560
      days, respectively. The protocol was well tolerated and should be studied further
      to evaluate the potential therapeutic gain of the addition of RT to chemotherapy
      for the treatment of canine lymphoma.

PMID- 19379301
TI  - Treatment of canine mast cell tumours with prednisolone and radiotherapy.
AB  - This retrospective study describes 35 dogs with non-resectable, grade I-III mast
      cell tumours on the head or limb treated with prednisolone (40 mg m(-2) daily)
      for 10-14 days prior to radiotherapy (4 x 800 cGy fractions at 7-day intervals)
      from a 4 MV linear accelerator. Prednisolone was continued at a reduced dose rate
      (20 mg m(-2)) during radiotherapy and for 2 months or longer afterwards. Eighteen
      of 24 tumours (75%) decreased in size in response to prednisolone treatment. By 6
      8 weeks following radiotherapy, 12 dogs had achieved a complete remission and 19
      a partial response. Two tumours remained static and two progressed during the
      course of treatment. The overall response rate was 88.5%. With long-term follow
      up, 11 dogs experienced local recurrence (n = 4), metastasis (n = 5) or both (n =
      2). The median progression-free interval was 1031 days (95% CI 277.44-1784.56,
      Kaplan-Meier), with 1- and 2-year progression-free rates of 60 and 52%,
      respectively. Tumour grade did not predict the prognosis for this group of dogs,
      but tumour location did affect the outcome. Dogs with tumours located on the limb
      survived longer than those with tumours on the head. The combination of
      prednisolone with radiotherapy appears to have a useful role in the management of
      measurable mast cell tumours sited on the head and distal extremities.

PMID- 19379302
TI  - Cardiac troponin I in canine patients with lymphoma and osteosarcoma receiving
      doxorubicin: comparison with clinical heart disease in a retrospective analysis.
AB  - The cumulative cardiotoxicity that occurs as a result of doxorubicin chemotherapy
      is irreversible and can affect both quality and quantity of life for the cancer
      patient. Cardiac troponin I (cTnI) is a sensitive and specific marker of
      cardiomyocyte death. The purpose of this retrospective study was to evaluate
      serum concentrations of cTnI in dogs with lymphoma or osteosarcoma given
      doxorubicin chemotherapy, and with known cardiac outcome, based on a minimum
      assessment by physical examination and thoracic radiography. Serum samples were
      also available for cTnI measurement from seven healthy dogs given intracoronary
      doxorubicin. Serial serum samples obtained before, during and after doxorubicin
      chemotherapy showed increased cTnI concentrations in some clinical patients
      following chemotherapy (P = 0.0083 compared to baseline), but this did not
      correlate with clinical signs of cardiomyopathy. In dogs that subsequently
      developed cardiomyopathy however, serum cTnI concentrations were elevated before
      clinical signs became evident (confirmed with echocardiography).

PMID- 19379303
TI  - Non-coherent light for photodynamic therapy of superficial tumours in animals.
AB  - Cultured 9L cells were incubated with varying concentrations of pheophorbide-a
      hexyl ether (HPPH) and then exposed to 665-nm red light from a non-coherent light
      source or a dye laser. Cell death was produced by both light sources, with the
      non-coherent light being most effective at the highest HPPH concentrations. To
      assess the feasibility of using the non-coherent light source for clinical
      photodynamic therapy (PDT), four dogs and three cats presenting with spontaneous
      superficial tumours were injected intravenously with 0.15 mg kg(-1) of HPPH, 1 h
      before their tumours were irradiated with 665-nm non-coherent light (50 mW cm(
      2), 100 J cm(-2)). Of the nine tumours treated, there were eight complete
      responses, all occurring in animals with squamous cell carcinoma. After 68 weeks
      of follow-up, the median initial disease-free interval had not been reached.
      These data suggest that non-coherent light sources may be efficacious for
      photodynamic therapy of spontaneous superficial tumours in animals, representing
      a cost-effective alternative to medical lasers in both veterinary and human
      oncology.

PMID- 19379304
TI  - Metastatic synovial cell sarcoma in two cats.
AB  - Synovial cell sarcoma (SCS) with metastasis to the regional lymph node was
      diagnosed in two cats. Synovial cell sarcomas are rare in cats and metastatic SCS
      has not previously been reported. In both cases, treatment consisted of limb
      amputation and adjuvant doxorubicin. Local tumour recurrence and pulmonary
      metastases were diagnosed in one cat 316 days postoperatively. This cat died of
      chronic renal failure 444 days after limb amputation. The second cat died of an
      acute pulmonary thromboembolism 41 days postoperatively without evidence of local
      tumour recurrence or metastatic disease.

PMID- 19379305
TI  - T-cell-derived malignant lymphoma in the boxer breed.
AB  - The boxer breed of dog is at high risk for a variety of neoplasms including
      lymphoma. In this observational study, tissue sections from boxer dogs with
      lymphoma were immunostained for T and B lymphocyte distinction, and the results
      compared with similar studies carried out on lymphoma tissues from temporally
      selected cohorts of golden retriever and rottweiler dogs. The frequency of T-cell
      lymphomas was significantly (P < 0.001 for all comparisons) higher in the boxers
      than in the rottweilers or golden retrievers. We are unaware of other reports
      linking immunotype of canine lymphoma with breed; whether other brachycephalic
      breeds of dogs have a similar preponderance of T-cell lymphoma awaits further
      study.

PMID- 19379306
TI  - Pulmonary metastatectomy in the management of four dogs with hypertrophic
      osteopathy.
AB  - The efficacy and outcome of pulmonary metastatectomy in the management of
      hypertrophic osteopathy (HO) secondary to metastatic osteosarcoma was
      retrospectively evaluated in four dogs. Metastatectomy was performed by
      subpleural enucleation, partial lung lobectomy or complete lung lobectomy through
      either a median sternotomy or thoracoscopically. Perioperative morbidity was
      minimal. Clinical signs associated with HO resolved within 24 h of pulmonary
      metastatectomy in all dogs. Durable remission of symptomatic HO was achieved in
      all dogs (range, 50-294 days), although recurrence of HO was noted in one dog,
      246 days post metastatectomy due to metastasis to the lungs and chest wall.
      Pulmonary metastatectomy resulted in a rapid and prolonged resolution of HO, and
      the clinical benefits of metastatectomy potentially exceed the morbidity
      associated with the surgical procedure.

PMID- 19379307
TI  - Evaluation of cyclooxygenase-1 and cyclooxygenase-2 expression and the effect of
      cyclooxygenase inhibitors in canine prostatic carcinoma.
AB  - Prostatic carcinoma occurs primarily in older castrated male dogs and is
      typically a fatal disease (most dogs die within few months after the initial
      diagnosis). Surgery, i.e., total prostatectomy, or radiation therapy is often not
      pursued due to risks of complications and a high rate of distant metastasis.
      Cyclooxygenase-2 (Cox-2) expression has been documented in several malignancies,
      including canine prostatic carcinoma. Cox-2 inhibition has been reported to have
      preventative effects on several human malignancies and has therapeutic effects on
      both laboratory and spontaneous tumour models. The purpose of this retrospective
      study was to evaluate Cox expression and the effects of Cox inhibitors on
      survival in dogs with prostatic carcinoma. 94.1 and 88.2% of the tumours
      expressed Cox-1 and Cox-2, respectively. Furthermore, dogs treated with Cox
      inhibitors (piroxicam or carprofen) lived significantly longer than untreated
      dogs, 6.9 versus 0.7 months (P < 0.0001), suggesting that Cox inhibitors may have
      an important role in canine prostate cancer therapy.

PMID- 19379308
TI  - Calponin expression and myoepithelial cell differentiation in canine, feline and
      human mammary simple carcinomas.
AB  - Calponin is a 34-kDa smooth muscle-specific protein that has been shown to be a
      highly sensitive marker of myoepithelial cells in canine, feline and human
      mammary tissue and tumours. The expression of calponin was studied in 15 canine,
      32 feline and 28 human simple mammary carcinomas using a monoclonal mouse
      antihuman calponin antibody and the avidin-biotin peroxidase complex (ABC)
      immunohistochemical technique. Calponin expression was compared with the
      expression of cytokeratin 14, a marker of normal mammary myoepithelial cells in
      the three species. Four different types of calponin-positive cells were
      identified: (1) Type 1: cytokeratin-14-positive pre-existing myoepithelial cells
      forming a continuous layer with images of focal disruptions; (2) Type 2:
      cytokeratin-14-positive isolated nests of fusiform, polygonal or round cells
      without atypia; (3) Type 3: cytokeratin-14-positive atypical cells
      indistinguishable from non-reactive atypical cells, which should have never been
      detected in haematoxylin and eosin-stained sections and (4) Type 4: cytokeratin
      14-negative stromal fusiform cells around the neoplastic growth or cell nests,
      identified as myofibroblasts. Calponin-negative and cytokeratin-14-positive
      atypical neoplastic cells were observed in three canine, 28 feline and two human
      carcinomas. The latter were indicative of altered expression of high-molecular
      weight cytokeratins in luminal epithelial-type simple carcinomas. Our findings
      show that calponin is a good marker of myoepithelial cell differentiation in
      feline, human and, particularly, canine simple carcinomas. The high number (six
      out of 15) of canine tumours with type 3 cells points to the need of both
      introducing calponin examination in the routine diagnostic schedule and
      performing further studies on its prognostic significance.

PMID- 19379309
TI  - Progression of a solitary, malignant cutaneous plasma-cell tumour to multiple
      myeloma in a cat.
AB  - An 11-year-old male domestic shorthair cat was examined because of a soft-tissue
      mass on the left tarsus previously diagnosed as a malignant extramedullary
      plasmacytoma. Findings of further diagnostic tests carried out to evaluate the
      patient for multiple myeloma were negative. Five months later, the cat developed
      clinical evidence of multiple myeloma based on positive Bence Jones proteinuria,
      monoclonal gammopathy and circulating atypical plasma cells. This case represents
      an unusual presentation for this disease and documents progression of an
      extramedullary plasmacytoma to multiple myeloma in the cat.

PMID- 19379310
TI  - Chronic lymphocytic leukaemia in a pot-bellied pig.
AB  - An 11-year-old, neutered male, Vietnamese pot-bellied pig was admitted for
      routine dental and foot care. As a part of routine geriatric evaluation, blood
      was submitted for a complete blood count and serum biochemical analysis. The
      blood count revealed a marked leucocytosis due to lymphocytosis. Further
      diagnostic evaluation, including abdominal and thoracic radiography, abdominal
      ultrasonography and blood lymphocyte immunophenotyping confirmed a diagnosis of
      chronic lymphocytic leukaemia of T-cell origin. Treatment was initiated with oral
      prednisone and cyclophosphamide. The pig did well on treatment for about 1 month
      after discharge but was then euthanized.

PMID- 19379311
TI  - A review of Doppler sonography for the assessment of tumour vascularity.
AB  - During the past decade, the vascular biology of cancer has become a highly
      interesting research field. To assess tumour vascularity and perfusion, various
      strategies such as computed tomography, magnetic resonance imaging and positron
      emission tomography have been investigated. Over the last years, important
      advances have taken place in the Doppler technology which dramatically improved
      its ability to evaluate the vascular system, even small and deep vessels. Doppler
      sonography provides a non-invasive means to assess the extent and morphology of
      tumour vascularity. This information is clinically important regarding diagnosis,
      prognosis and response to treatment, particularly in connection with the
      development of novel angiogenesis inhibitors. This article describes the
      different Doppler technologies most commonly used in human and experimental
      animal oncology. Based on in vivo tumour models and extensive clinical experience
      in humans, their significance and potential clinical applications are
      illustrated. First clinical reports in veterinary medicine are also reviewed.

PMID- 19379312
TI  - The comparative biology of skeletal metastasis.
AB  - Bone metastasis, a very common sequelae of cancer, is often associated with great
      morbidity. Understanding the biology of bone metastases may lead to therapeutic
      interventions to target the metastases. In addition to replacing bone marrow
      elements, the presence of tumour cells in bone modulates the normal bone
      remodelling process. Some tumours result in primarily osteolytic bone lesions,
      whereas others are associated with osteoblastic bone lesions. In either case, the
      resulting changes in the bone structure result in weakened bone that induces pain
      and is predisposed to fracture. The mechanisms through which cancer cells
      modulate bone remodelling are not clearly defined, but ongoing research using a
      variety of animal models will hopefully provide clues to prevent or slow the
      progress of bone metastases.

PMID- 19379313
TI  - Telomerase activity and related properties of normal canine lymph node and canine
      lymphoma.
AB  - Telomerase activity (TA) and the expression of p16(INK4), telomerase reverse
      transcriptase catalytic subunit (TERT) and proliferating cell nuclear antigen
      (PCNA) were analysed in lymph nodes from clinically normal dogs and from dogs
      with lymphoma. Telomere lengths were measured in 12 histologically normal lymph
      nodes. These data were related to the overall survival time of the lymphoma
      patients given chemotherapy, in an effort to identify prognostic significance of
      the measured variables. There was no significant difference between TA of normal
      lymph nodes (n = 16) and lymphoma lymph nodes (n = 6). PCNA expression was
      significantly higher in lymphoma (n = 30) than in normal lymph nodes (n = 10),
      but TERT expression was not. Expression of p16(INK4) was not significantly
      different between normal and lymphoma lymph nodes. TA and p16(INK4) expression
      were inversely correlated within the normal lymph nodes studied. Telomere lengths
      in normal lymph nodes were consistent with previous studies. No variables
      examined had any correlation with survival of the lymphoma patients given
      chemotherapy. The role of p16(INK4) in the regulation of TA warrants further
      investigation.

PMID- 19379314
TI  - Nuclear scanning with 99mTc-HDP for the initial evaluation of osseous metastasis
      in canine osteosarcoma.
AB  - The purpose of this retrospective analysis was to evaluate the use of nuclear
      scintigraphy in determining the rate of secondary sites of osseous malignancy at
      initial presentation in dogs with osteosarcoma. Radiographs of suspicious
      secondary lesions were reviewed and placed into four separate categories: benign
      lesions; no lesion seen on radiographs; subtle radiographic changes suggestive
      of, but not conclusive for, metastasis; and metastatic lesions highly suspected
      on radiographs. Three hundred and ninety-nine dogs were evaluated by technetium
      nuclear scanning for suspected osteosarcoma. Three hundred and twenty-six of 399
      dogs (82%) had only one apparent site on the nuclear scan, whereas 72 dogs (18%)
      had more than one suspicious site on the nuclear scans. Highly suspected
      secondary metastatic lesions were detected by nuclear scans in 7.8% of cases.
      Although interpretation of nuclear scans is subjective, this study showed a 7.8%
      chance of detecting unsuspected osseous metastasis with nuclear scans in canine
      osteosarcoma patients on initial presentation.

PMID- 19379315
TI  - In vitro effects of 2-methoxyestradiol on canine tumour cells.
AB  - The in vitro antiproliferative, apoptotic and cell-cycle effects of 2
      methoxyestradiol (2ME(2)), an endogenous oestrogen metabolite, were investigated
      using a variety of canine tumour cell lines. The cells were cultured under
      standard conditions and incubated with varying concentrations of 2ME(2).
      Inhibition of tumour cell proliferation was evaluated using a tetrazolium-based
      colorimetric assay. DNA content analysis was performed using propidium iodide
      staining and flow cytometry. Cytologic analysis with Leukostat staining solution
      and Hoechst 33342 staining and Annexin V-fluorescein isothiocyanate (FITC)
      fluorescence were used to quantify cell-cycle distribution and apoptosis
      induction. Tumour cell proliferation was inhibited by 50% at concentrations of
      2ME(2) ranging from 0.88 to 7.67 microM, depending on the cell line tested.
      Profound G(2)/M phase arrest, an increase in binucleate cells and induction of
      apoptosis were observed in all cell lines tested, in a dose-dependent manner.
      Based on these results, this compound has potential as an agent for the treatment
      of canine cancer and warrants further investigation. The canine lymphoma cell
      line, 1771, was inhibited at concentrations that may be achievable in vivo.

PMID- 19379317
TI  - Comparative oncology--new and expanding opportunities for research.

PMID- 19379318
TI  - Dexamethasone treatment of a canine, but not human, tumour cell line increases
      chemoresistance independent of P-glycoprotein and multidrug resistance-related
      protein expression.
AB  - Glucocorticoids are often used in veterinary cancer patients because of their
      anti-inflammatory actions, appetite-stimulating effects, ability to decrease
      nausea and vomiting associated with some chemotherapy agents, and, in some
      instances, for their cytotoxic actions on susceptible tumour cells. Veterinary
      oncologists may not consider the possibility that the use of glucocorticoids may
      adversely affect response to chemotherapy. There is evidence that glucocorticoids
      can up-regulate the expression of multidrug resistance genes in some tissues.
      Whether or not glucocorticoid-induced expression of multidrug resistance proteins
      occurs in tumour cells is not presently known. The purpose of this study was to
      determine if dexamethasone induces P-glycoprotein (P-gp) or multidrug resistance
      related protein 1 (MRP1) in tumour cell lines. A canine osteosarcoma cell line
      (OS2.4) and a human myeloid leukaemia cell line 60 (HL60) were treated in culture
      with dexamethasone. The presence of a glucocorticoid receptor was confirmed in
      both cell lines by reverse-transcriptase polymerase chain reaction. Western blots
      for P-gp and MRP1 expression were performed on vehicle-treated and dexamethasone
      treated cells. Sensitivity towards several chemotherapeutic drugs (cisplatin (cis
      diamminedichloroplatinum), doxorubicin, methotrexate and vincristine) was
      determined by 3-(4,5-dimthylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay. While dexamethasone treatment of OS2.4 cells increased the resistance to
      cisplatin and methotrexate, an increase in P-gp or MRP1 expression was not
      observed. Dexamethasone-treated HL60 cells did not develop chemoresistance and
      did not show increased expression of P-gp or MRP1.

PMID- 19379319
TI  - Preclinical evaluation of 5-aminolevulinic acid-based photodynamic therapy for
      canine transitional cell carcinoma.
AB  - As a prelude to photodynamic therapy, 5-aminolevulinic acid (ALA) was given
      orally to healthy dogs. ALA-induced protoporphyrin IX (PpIX) fluorescence
      significantly increased in the mucosa of the urinary bladder in an ALA dose
      dependent fashion. Vomiting occurred after ALA administration in 70% of the dogs
      but did not affect PpIX fluorescence. ALA-based photodynamic therapy (PDT) of the
      urinary bladder in healthy dogs caused only submucosal oedema within the bladder
      wall. No haematologic or serum biochemistry abnormalities were observed after ALA
      administration. Microscopic haematuria was observed in all the dogs after PDT but
      was mild and self limiting. ALA-based PDT was administered to six dogs with
      transitional cell carcinoma (TCC) of the lower urinary tract. ALA-based PDT
      resulted in tumour progression-free intervals from 4 to 34 weeks in five dogs;
      one dog with pre-existing hydronephrosis died shortly after PDT. Dogs with TCC
      represent an outbred, spontaneous, tumour model for developing PDT protocols for
      humans with bladder cancer.

PMID- 19379320
TI  - Intravenous administration of 9-aminocamptothecin to dogs with lymphoma.
AB  - A colloidal dispersion formulation of 9-aminocamptothecin (9-AC) was administered
      intravenously to 10 dogs with previously untreated, spontaneously occurring,
      multicentric lymphoma. The dogs received a 72-h infusion of 9-AC at a rate of
      46.5-51.25 microg m(-2) h(-1) (total dose range 3.35-3.69 mg m(-2)). This dose
      range was associated with myelosuppression, consisting principally of neutropenia
      with a nadir at 7 days following the start of infusion. Neutropenia and
      thrombocytopenia were the most common toxicoses and are most likely to be dose
      limiting toxicities; low-grade gastrointestinal signs were rarely seen.
      Concentrations of 9-AC lactone, as well as clinical toxicities, compare
      favourably with those found in humans. Tumour responses were seen in all treated
      dogs. Response to other chemotherapy, following cessation of 9-AC treatment, was
      not obviously compromised even in dogs clinically resistant to 9-AC. 9-AC is a
      novel treatment drug for canine lymphoma, which appears to show great promise.

PMID- 19379321
TI  - Postoperative radiotherapy and mitoxantrone for anal sac adenocarcinoma in the
      dog: 15 cases (1991-2001).
AB  - The medical records of 15 dogs with anal sac adenocarcinoma (ASAC) treated with
      concurrent curative-intent radiotherapy and mitoxantrone (MX) after surgical
      removal of the primary tumour were reviewed retrospectively. Radiation was
      prescribed at 15 daily fractions of 3.2 Gy for a total dose of 48 Gy. MX was
      given intravenously at a dosage of 5 mg m(-2) every 3 weeks for five treatment
      sessions. Twelve dogs received pelvic irradiation to include the regional lymph
      nodes (LNs) and three received radiation only to the perineum. At the time of
      diagnosis, four dogs were hypercalcaemic and seven dogs presented with regional
      LN metastasis. All the dogs with regional LN metastasis received pelvic
      irradiation, and in three cases, metastatic LNs were treated in the macroscopic
      disease setting. The median event-free survival was 287 days, and the median
      overall survival was 956 days. Acute and chronic radiation complications were
      common and non-life threatening, although chronic complications contributed to
      the decision to euthanize two dogs. The results observed in this retrospective
      analysis compare favourably with cases of ASAC in the literature related to
      treatment with surgery and/or chemotherapy.

PMID- 19379322
TI  - Enhanced bioavailability of oral docetaxel by co-administration of cyclosporin A
      in dogs and rats.
AB  - Pharmacokinetic and pharmacodynamic endpoints of intravenously and orally
      administered docetaxel (DT) with or without oral cyclosporine were characterized
      in rats and dogs. Plasma samples were analysed for DT using liquid chromatography
      mass spectrometry. DT area-under-the-concentration-time curve, plasma clearance
      and maximum serum clearance were significantly affected by cyclosporine in rats
      (P <or= 0.0005). Bioavailability of DT alone and DT combined with cyclosporine
      was 1.3 and 82%, respectively, in rats. In dogs, cyclosporine resulted in a 14-17
      fold increase in peak DT concentrations (P < 0.0005) and area-under-the-curve (P
      < 0.0005), and a 17-fold reduction in DT clearance (P < 0.005). Bioavailability
      of DT alone was 18 +/- 16% and statistically exceeded 100% (251 +/- 104%) when
      combined with cyclosporine in dogs. Two of the six dogs receiving DT plus
      cyclosporine developed neutropenia, and one of the six dogs experienced vomiting
      and diarrhoea. Cyclosporine significantly alters the disposition of oral DT in
      dogs and rats, such that clinically relevant serum concentrations are achievable.

PMID- 19379323
TI  - Sarcoma development after radiotherapy in two dogs.
AB  - Two dogs were treated with a hypofractionated course of radiotherapy following
      surgical excision of an intermediate grade mast cell tumour and a round cell
      tumour, respectively. Both dogs developed a sarcoma of the bone, within the
      irradiated site, several years after the initial radiotherapy treatment. Bone
      tumours arising within a previously irradiated area are well-recognized late
      radiotherapy side-effect in humans but have been reported infrequently in dogs.
      These are the first case reports to describe bone sarcomas in the appendicular
      skeleton at a site, which had been previously treated by a hypofractionated
      course of radiotherapy for an unrelated tumour.

PMID- 19379324
TI  - A landmark in Veterinary and Comparative Oncology.

PMID- 19379325
TI  - Papillomavirus and disease in humans and animals.
AB  - Papillomavirus (PV) induces exophytic lesions (papillomas, warts) and flat
      lesions (flat warts, cervical intraepithelial neoplasia) in cutaneous and mucosal
      epithelia. The lesions are usually benign and generally regress without eliciting
      any serious clinical problems in a host but occasionally persist. Persistent
      lesions can be debilitating and can also provide a focus for malignant
      transformation to squamous cell carcinoma, particularly in the presence of
      environmental or genetic cofactors. This has been experimentally demonstrated in
      animals, particularly in cattle, where bovine PV (BPV)-induced papillomas
      progress to cancer of the upper gastrointestinal (GI) tract and the urinary
      bladder in animals exposed to bracken fern in the pasture, and in rabbits, where
      the progression of skin papillomas to squamous cell carcinoma depends on a
      particular variant of cottontail rabbit PV (CRPV) and on the major
      histocompatibility complex (MHC) class II haplotype of the animal. In this
      review, various aspects of the biology of BPV and CRPV are described and compared
      with those of human PV, including viral genome structure, regulation of
      transcription of the viral oncogenes, function of the viral oncoproteins, co
      operation between virus and cofactors, virus latency, immunity and vaccination.

PMID- 19379326
TI  - Quercetin induces structural chromosomal aberrations and uncommon rearrangements
      in bovine cells transformed by the E7 protein of bovine papillomavirus type 4.
AB  - Bovine papillomavirus type 4 (BPV-4) and bracken fern are cofactors in the
      carcinogenesis of the upper gastrointestinal (GI) tract of cattle. An
      experimental in vitro model system has been developed to analyse the co-operation
      between the viral transforming protein E7, the cellular ras oncogene and
      quercetin, one of the mutagens of bracken fern, during neoplastic progression of
      primary bovine cells. We now report cytogenetic studies of these cells at
      different stages of malignant transformation: parental primary non-transformed
      PalF cells; E7R cells transformed by BPV-4 E7 and activated ras but not
      tumorigenic, and tumorigenic E7Q cells derived from E7R cells after treatment
      with quercetin. All cell lines presented increased numbers of aneuploid cells.
      The rate of structural chromosomal aberrations observed was increased in
      transformed cells. In addition, E7Q cells showed chromosomes with peculiar
      rearrangements, which resulted in metacentric and submetacentric marker
      chromosomes, with an increase in the mean chromosome arm number. These markers
      were the products of possible centric fusions. These aberrations and
      rearrangements were distributed throughout the karyotype, no specific chromosome
      was involved and the heterochromatic centromeric regions appeared to be
      preserved.

PMID- 19379327
TI  - Clastogenic effect of bracken fern (Pteridium aquilinum v. arachnoideum) diet in
      peripheral lymphocytes of human consumers: preliminary data.
AB  - Ingestion of bracken fern (Pteridium aquilinum v. arachnoideum) is associated
      with digestive tract cancer in different regions of Japan, Venezuela and Brazil.
      In view of reports that dietary bracken fern causes chromosomal instability in
      cattle, the clastogenic effect of bracken fern was investigated, in a preliminary
      study, in peripheral lymphocytes obtained from habitual consumers and a control
      group of non-consumers, which were carefully investigated about cancer history or
      family cancer history, negative in both cases, using protocols comparable to
      those previously described in studies in cattle raised on bracken pastures.
      Cytogenetic analysis showed significant increased levels of chromosomal
      abnormalities, such as chromatid breaks, in cultured peripheral lymphocytes of
      the consumer group. There was no correlation with subjects, gender, smoking
      habits or alcohol consumption, and the only correlation was with prolonged
      exposure to dietary bracken.

PMID- 19379328
TI  - Sequence and structural analysis of the presumed downstream promoter of the
      canine mdr1 gene.
AB  - The product of the canine mdr1 gene, P-glycoprotein (P-gp), plays an important
      role in chemotherapeutic drug resistance of several canine tumours. Increased
      expression of P-gp by tumour cells is associated with the multidrug-resistant
      phenotype. Because of its importance in cancer chemotherapy, a great deal is
      known about the regulation of mdr1 gene expression in human cancer patients and
      rodent cancer models. In contrast, there is no information regarding the
      regulation of P-gp expression in dogs. Initial information regarding the
      regulation of mdr1 gene expression can be gained by evaluating the mdr1 promoter.
      The downstream promoter of the canine mdr1 gene was sequenced. Several regulatory
      elements were identified, including an AP-1 site, AP-2 site and SP-1 site. The
      presumed canine mdr1 promoter was similar to that of other species; however, low
      overall sequence homology may suggest that aspects of P-gp regulation are
      distinctive in dogs.

PMID- 19379329
TI  - Cloning, expression and in vitro evaluation of recombinant canine Tum5, an
      angiostatic domain of mammalian type IV collagen.
AB  - The process of new blood vessel formation within and around neoplastic tissue,
      termed angiogenesis, is a significant factor in the development, progression and
      metastasis of malignant tumours in all species. A major cause of death in cancer
      patients is the development of treatment-resistant metastatic disease, which may
      be avoided by therapies that target the genetically stable population of vascular
      endothelial cells within tumours. Tumstatin is a small protein formed by the
      cleavage of the alpha-3 subunit of the non-collagenous domain of mammalian type
      IV collagen. Recombinant human Tumstatin has been shown to have potent
      angiostatic properties in vitro and in vivo. Tumstatin is a potent initiator of
      apoptosis and inhibits the proliferation and migration of vascular endothelial
      cells in cell culture. Recently, a fragment of Tumstatin, termed Tum5, has been
      shown to have biologic activity similar to the parent compound. The systemic
      administration of angiostatic proteins like Tum5 may result in the remission of
      established tumours, while preventing or delaying the onset of clinically
      detectable metastasis. Recombinant canine Tum5 (cTum5) was cloned and its protein
      expression induced in a prokaryotic vector. The resulting cTum5 protein caused
      dose-dependent inhibition of vascular endothelial cells in vitro, which appears
      to be mediated through apoptosis.

PMID- 19379330
TI  - Immunohistochemical characterization of canine prostatic carcinoma and
      correlation with castration status and castration time.
AB  - The purpose of this study was to characterize canine prostate cancer using
      immunohistochemical staining specific for acinar and urothelial/ductal tissue and
      correlate these results with the dogs' castration status/castration time. Seventy
      dogs with prostate cancer were included, 71% were castrated and 29% were intact.
      Compared with an age-matched control population, castrated dogs were at increased
      risk of prostate cancer, odds ratio 3.9. Immunohistochemical staining was
      performed on 58 cases. Forty-six of the 58 stained positive for cytokeratin 7 (CK
      7) (ductal/urothelial origin) and one of the 58 stained positive for prostate
      specific antigen. Dogs with CK 7-positive tumours were younger when castrated
      than dogs with CK 7-negative tumours, 2 versus 7 years (P = 0.03); dogs castrated
      at <or=2 years of age were more likely to be CK 7-positive (P = 0.009). These
      results show that most canine prostatic carcinomas are of ductal/urothelial,
      androgen-independent origin. This is consistent with the epidemiological
      findings, showing increased risk in castrated dogs. Canine prostate cancer may,
      therefore, not be a realistic model for the human disease.

PMID- 19379331
TI  - Resolution of persistent oral papillomatosis in a dog after treatment with a
      recombinant canine oral papillomavirus vaccine.
AB  - This report describes a 16-month-old female, otherwise seemingly healthy,
      Siberian husky dog with severe oral papillomatosis that did not regress
      spontaneously and was refractory to surgical treatment over a 6-month period.
      Regression of the papillomas was achieved by administering a series of
      experimental vaccinations starting at the time of the last surgery. The vaccine
      consisted of systemically administered canine oral papillomavirus major coat
      protein L1 that has been shown to self-assemble into virus-like particles. They
      cause a humoral response that has been shown to prevent the onset and development
      of papillomas. In this case, however, following unsuccessful surgical treatment,
      the vaccine acted therapeutically, causing the papillomas that had regrown to
      shrink. No side-effects were noted.

PMID- 19379336
TI  - We should strive for optimal hemodialysis: a criticism of the hemodialysis
      adequacy concept.
AB  - Adequacy of hemodialysis is frequently equated with Kt/V(urea) , the amount of
      urea clearance (K) multiplied by time (t) and divided by urea distribution volume
      (V). Several formulas have been developed to calculate Kt/V(urea) from the pre-
      and post-dialysis urea concentrations. In three-times-weekly hemodialysis, a
      single pool (spKt/V(urea)) value of 1.3 per treatment is commonly considered to
      indicate adequate therapy. Despite providing the recommended spKt/V(urea) of 1.3
      per treatment, short dialysis with rapid ultrafiltration is associated with
      multiple intradialytic and interdialytic complications. Patients experience
      cramps, nausea, vomiting, headaches, fatigue, hypotensive episodes during
      dialysis, and hangover after dialysis; patients remain fluid overloaded with
      subsequent poor blood pressure control, left ventricular hypertrophy, diastolic
      dysfunction, and high cardiovascular mortality. According to Webster's
      dictionary, "optimal" means most desirable or satisfactory; "adequate" means
      sufficient for a specific requirement or barely sufficient or satisfactory.
      Optimal dialysis is the method of dialysis yielding results that cannot be
      further improved. New approaches, including hemeral quotidian or long nocturnal
      dialysis, provide opportunities to abandon the notion that adequate dialysis is
      "good enough" for our patients. Optimal dialysis should be our goal. Dialysis
      sessions should be long and frequent enough to provide excellent intra- and
      interdialytic tolerance of hemodialysis, normalization of serum calcium and
      phosphorus, blood pressure control, normal myocardial morphology and function,
      and hormonal balance, and to eliminate all, even subtle, uremic symptoms.

PMID- 19379338
TI  - The decline in residual renal function in hemodialysis is slow and age dependent.
AB  - BACKGROUND: Persons on peritoneal dialysis and hemodialysis with preserved
      residual renal function experience lower mortality rates than those without.
      Previous studies have shown slower rates of decline of residual renal function
      for peritoneal dialysis (PD)(2 to 3% decrease/month), compared with hemodialysis
      (HD)(6 to 7% decrease/month). However, our clinical observations suggested a
      lower rate of decline in hemodialysis patients. METHODS: We evaluated data in 174
      hemodialysis patients cared for from January 2000 through October 2001. Eighty
      seven (50%) patients had at least two timed quarterly urine collections to
      estimate the rate of change of residual renal function over time (urea clearance,
      or KrU). All patients underwent thrice-weekly hemodialysis using polysulfone
      dialyzers with formaldehyde reprocessing. The rate of decline of residual renal
      function and the effect of KrU on laboratory variables were estimated using a
      random effects (MIXED) model, adjusting for the effects of age, sex, race,
      diabetes, and dialysis vintage. RESULTS: The mean KrU at baseline was 3.5 mL/min.
      Men (P < 0.001) and persons of shorter vintage (P < 0.0001) had more residual
      renal function at baseline. The estimated rate of decline of residual renal
      function was - 0.07 mL/min/month (- 1.9% decrease/month). The rate of decline in
      residual renal function was unaffected by sex, race, diabetes, or vintage,
      although the rate of decline was significantly attenuated among older individuals
      (age x time interaction, P = 0.01). Serum phosphorus (P = 0.03) and the calcium x
      phosphorus product (P = 0.009) increased over time and were influenced by the
      level of residual renal function (P = 0.06 and P = 0.006, respectively). Residual
      renal function did not influence the rate of change of other laboratory
      variables. CONCLUSIONS: In an ethnically diverse cohort of hemodialysis patients,
      the rate of decline of residual renal function was relatively slow and age
      dependent, as well as consistent with values others have reported for patients on
      peritoneal dialysis. Universal use of biocompatible dialyzers and bicarbonate
      dialysate may have contributed to differences discussed in prior reports.
      Residual renal function attenuated the increase in calcium-phosphorus product
      over time. A better understanding of the determinants of the rate of decline in
      residual renal function, and the specific benefits afforded to patients via
      maintenance of residual renal function, would help to inform the debates on
      timing of initiation and various dosing strategies in hemodialysis.

PMID- 19379339
TI  - Relationship between vascular access flow and hemodynamically significant
      stenoses in arteriovenous grafts.
AB  - BACKGROUND: Vascular access dysfunction is a major source of hemodialysis patient
      morbidity. The NKF K/DOQI Guidelines promote access flow monitoring as the most
      preferred access surveillance method and have established access flow thresholds
      for fistulography: an absolute threshold of 600 ml/min and a dynamic threshold of
      flow less than 1000 ml/min that has decreased by more than 25% over 4 months. The
      Guidelines apply universally to accesses of different types, sizes, locations,
      and initial flow rates. METHODS: This article studies the application of access
      flow guidelines with human experimental data, animal experimental data, and a
      mathematical model of the arteriovenous graft system. RESULTS AND CONCLUSIONS:
      Analysis of experimental data and the mathematical model shows that a 20 to 30%
      and greater decrease in graft flow generally suggests the appearance of
      hemodynamically significant stenosis as defined by flow criteria. The model
      suggests that not all 50 to 60% stenoses may be hemodynamically significant or
      the most flow limiting. The mathematical model also suggests that positive
      predictive value of access surveillance may be increased for high-flow upper arm
      grafts by increasing the dynamic K/DOQI threshold from 1000 ml/min to 1200
      ml/min.

PMID- 19379340
TI  - Toward a continuous quality improvement paradigm for hemodialysis providers with
      preliminary suggestions for clinical practice monitoring and measurement.
AB  - BACKGROUND: Consensus processes using the clinical literature as the primary
      source for information generally drive projects to draft clinical practice
      guidelines (CPGs). Most such literature citations describe special projects that
      are not part of an organized quality management initiative, and the
      publication/review/consensus process tends to be long. This project describes an
      initiative to develop and explore a flexible and dedicated data-driven paradigm
      for deciding new CPGs that could be rapidly responsive to changing medical
      knowledge and practice. METHODS: Candidate Clinical Practice Monitoring Measures
      (CPMM) were selected using a large, national database according to the natures
      and strengths of their associations with mortality risk among patients during
      1994. Thresholds above or below which risk of death increased were evaluated for
      each CPMM using risk profile charts and spline functions. The fractions of
      patients outside of those thresholds in each dialysis unit (the %Var) were
      determined for the years 1993, 1994, and 1995. A standardized mortality ratio
      (SMR) was also determined for each year for each facility. The associations
      between the %Var and SMR were evaluated in several single-variable and
      multivariable statistical models. RESULTS: Eleven CPMM were selected and
      evaluated based on their associations with death risk. These included the urea
      clearance x dialysis time product (Kt); the concentrations of albumin, potassium,
      phosphate, bicarbonate, hemoglobin, neutrophils, and lymphocytes in the blood;
      the body weight/height ratio; diastolic blood pressure; and vascular access type.
      Even though the CPMM were strongly associated with death risk among patients, the
      %Var were weakly and inconsistently associated with SMR among facilities.
      CONCLUSIONS: The paradigm was flexible, easy to implement, quickly executed, and
      potentially able to accommodate evolving medical practice assuming the
      availability of large database systems such as this. The primary associates of
      death risk were easily identified and the thresholds easily adopted. The SMR and
      %Var from the CPMM were only weakly associated, however, suggesting that one
      cannot be reliably predicted from the other. As such, quality management programs
      should likely monitor both the processes and outcomes of care among dialysis
      facilities.

PMID- 19379341
TI  - Back to the future: middle molecules, high flux membranes, and optimal dialysis.
AB  - Middle molecules can be defined as compounds with a molecular weight (MW) above
      500 Da. An even broader definition includes those molecules that do not cross the
      membranes of standard low-flux dialyzers, not only because of molecular weight,
      but also because of protein binding and/or multicompartmental behavior. Recently,
      several of these middle molecules have been linked to the increased tendency of
      uremic patients to develop inflammation, malnutrition, and atheromatosis. Other
      toxic actions can also be attributed to the middle molecules. In the present
      publication we will consider whether improved removal of middle molecules by
      large pore membranes has an impact on clinical conditions related to the uremic
      syndrome. The clinical benefits of large pore membranes are reduction of uremia
      related amyloidosis; maintenance of residual renal function; and reduction of
      inflammation, malnutrition, anemia, dyslipidemia, and mortality. It is concluded
      that middle molecules play a role in uremic toxicity and especially in the
      processes related to inflammation, atherogenesis, and malnutrition. Their removal
      seems to be related to a better outcome, although better biocompatibility of
      membranes might be a confounding factor.

PMID- 19379342
TI  - Comparison between United States and Japanese dialysis mortality rates: useless
      or useful?

PMID- 19379343
TI  - International comparisons of survival on dialysis: are they reliable?
AB  - Sharp discrepancies between reported survivals on maintenance hemodialysis in the
      United States compared with Europe and Japan have provoked broad criticism of the
      American system of treating irreversible uremia. Although this negative view of
      renal therapy in the United States is supported by the National Kidney Foundation
      (NKF), consensus conferences of the National Institutes of Health (NIH), and
      numerous social critics of the American health care system, the contention has
      not been sustained by appropriate statistical analysis. The United States has the
      world's highest treatment rate for incident kidney failure - double that in
      Europe. This is mainly due to universal acceptance for uremia therapy. In
      comparisons with Japan, studies have not taken into account unique aspects of
      Japanese health care and genetic differences between sampled cohorts of studied
      kidney patients. In fact, no properly conducted analysis has found that the
      quality of uremia therapy in the U.S. has been inferior to that of anywhere else.
      While the allegation may yet be proven true, thus far there is no scientific
      basis for indicting dialysis in the United States as lacking in quality or
      quantity when ranked with other industrialized nations.

PMID- 19379344
TI  - Differences in dialysis practice are the main reasons for the high mortality rate
      in the United States compared to Japan.
AB  - The cumulative survival of Japanese hemodialysis patients is more than 2.5 times
      better than that of dialysis patients in the United States (U.S.). The difference
      is particularly pronounced in older patients, being 4 times better in patients
      over the age of 50 years. The mortality in U.S. patients has increased from 10 to
      25% over the last three decades, but has remained stable at around 10% in Japan.
      There is no obvious difference in patient selection. The Japanese accept almost
      as high a proportion of diabetic patients as does the United States, and the mean
      age of incident patients is higher in Japan. Renal transplantation, virtually
      absent in Japan, should increase mortality in U.S. dialysis patients by removing
      patients with the highest probability of survival, but even if one adds surviving
      transplant patients and studies prevalent populations, the survival rate is much
      better in Japan. Genetic factors are unlikely to explain differences in
      mortality, as older Americans live much longer than older Japanese. We speculate
      that the difference lies in the practice of dialysis. Patients in the United
      States are generally treated by much faster and shorter dialysis than in Japan.
      This puts a severe burden on the cardiovascular system of older patients, leading
      to the poorer survival rate. Japanese physicians also appear to be better trained
      in dialysis and to spend more time with their patients. The nursing shortage in
      the United States may also contribute to the increased mortality. Whatever the
      explanations, the U.S. dialysis community must work to equal and, hopefully,
      surpass the now superior survival of Japanese dialysis patients.

PMID- 19379345
TI  - Hemodialysis quiz: questions.

PMID- 19379346
TI  - Hemodialysis abstracts from the 23rd annual dialysis conference.

PMID- 19379347
TI  - Hemodialysis quiz: answers.

PMID- 19379349
TI  - Fallacies of high-speed hemodialysis.
AB  - Chronic hemodialysis sessions, as developed in Seattle in the 1960s, were long
      procedures with minimal intra- and interdialytic symptoms. Financial and
      logistical pressures related to the overwhelming number of patients requiring
      hemodialysis created an incentive to shorten dialysis time to four, three, and
      even two hours per session in a thrice weekly schedule. This method spread
      rapidly, particularly in the United States, after the National Cooperative
      Dialysis Study suggested that time of dialysis is of minor importance as long as
      urea clearance multiplied by dialysis time and scaled to total body water
      (Kt/V(urea)) equals 0.95-1.0. This number was later increased to 1.3, but the
      assumption remained unchanged that hemodialysis time is of minimal importance as
      long as it is compensated by increased urea clearance. Patients accepted short
      dialysis as a godsend, believing that it would not be detrimental to their well
      being and longevity. However, Kt/V(urea) measures only removal of low molecular
      weight substances and does not consider removal of larger molecules. Besides, it
      does not correlate with the other important function of hemodialysis, namely
      ultrafiltration. Whereas patients with substantial residual renal function may
      tolerate short dialysis sessions, the patients with little or no urine output
      tolerate short dialyses poorly because the ultrafiltration rate at the same
      interdialytic weight gain is inversely proportional to dialysis time. Rapid
      ultrafiltration is associated with cramps, nausea, vomiting, headache, fatigue,
      hypotensive episodes during dialysis, and hangover after dialysis; patients
      remain fluid overloaded with subsequent poor blood pressure control, left
      ventricular hypertrophy, diastolic dysfunction, and high cardiovascular
      mortality. Short, high-efficiency dialysis requires high blood flow, which
      increases demands on blood access. The classic wrist arteriovenous fistula, the
      access with the best longevity and lowest complication rates, provides
      "insufficient" blood flow and is replaced with an arteriovenous graft fistula or
      an intravenous catheter. Moreover, to achieve high blood flows, large diameter
      intravenous catheters are used; these fit veins "too tightly," so predispose the
      patient to central-vein thrombosis. Longer hemodialysis sessions (5-8 hrs, thrice
      weekly), as practiced in some centers, are associated with lower complication
      rates and better outcomes. Frequent dialyses (four or more sessions per week)
      provide better clinical results, but are associated with increased cost. It is my
      strong belief that a wide acceptance of longer, gentler dialysis sessions, even
      in a thrice weekly schedule, would improve overall hemodialysis results and
      decrease access complications, hospitalizations, and mortality, particularly in
      anuric patients.

PMID- 19379350
TI  - Choice reaction time and adequacy of dialysis: a new application of an old
      method.
AB  - BACKGROUND: Choice Reaction Time (CRT) is the time it takes for a subject to
      accurately respond to a flashing panel of lights. The CRT has been used to assess
      the quality of dialysis in hemodialysis patients and to assess the neurological
      impairments in patients with Parkinson's disease. METHODS: Three groups of end
      stage renal disease (ESRD) patients on three different renal replacement
      therapies were tested using CRT: intermittent peritoneal dialysis (IPD, n = 11),
      thrice weekly hemodialysis (HD, n = 22), and well-functioning kidney transplant
      (Tx, n = 6). A group of volunteers with normal renal function (NL, n = 12) was
      also tested. RESULTS: The CRT was significantly longer in IPD patients (618 +/-
      89 ms) than observed in the other three groups (p < 0.0001). CRT in HD patients
      was 461 +/- 50 ms, which was significantly longer than in Tx patients (396 +/- 25
      ms, p = 0.05). However, the CRT in the Tx patients was no different from the NL
      (382 +/- 22, p = 0.32). There was a strong negative correlation between CRT and
      weekly creatinine clearance in the IPD group (r =- .96) and between the dialysis
      index and CRT in HD (r =- 0.79). CONCLUSIONS: CRT may be a useful tool in
      assessing the adequacy of dialysis.

PMID- 19379351
TI  - Severe cortical and trabecular osteopenia in secondary hyperparathyroidism.
AB  - BACKGROUND: Peripheral quantitative computed tomography (pQCT) provides real
      volumetric bone density values, not only of the total, but also of trabecular and
      cortical bone, separately. In addition, it provides data on bone geometry that
      can be related to the risk of fracture. METHODS: Total, cortical, and trabecular
      volumetric bone mineral densities (BMD), as well as the main geometric parameters
      (cross-sectional area, cortical area, trabecular area, and cortical thickness)
      were assessed by pQCT at the distal radius in 24 hemodialysis patients affected
      by severe secondary hyperparathyroidism (PTH, mean +/- SD: 1444 +/- 695 pg/mL).
      The strength-strain index (SSI), a biomechanical parameter describing bone
      fragility, was also determined. RESULTS: Compared with a control group of 64
      healthy age-matched subjects, volumetric BMD (mg/cm(3)) was significantly reduced
      in all patients (total BMD: 243 +/- 87 vs. 405 +/- 138, cortical BMD: 605 +/- 218
      vs. 856 +/- 204, trabecular BMD: 95 +/- 51 vs. 182 +/- 75). Cortical area and
      cortical thickness showed significant modifications, while cross-sectional area
      did not. SSI was significantly reduced (547 +/- 125 vs. 927 +/- 306 mm(3)). PTH
      levels showed a significant inverse correlation with cortical BMD (r = -0.56),
      cortical thickness (r = -0.46), cortical area (r = -0.61), and SSI (r = -0.54).
      Quantitative analysis of bone demonstrated cortical porosity. CONCLUSIONS: In
      dialysis patients with severe secondary hyperparathyroidism, pQCT showed a
      significant cortical osteopenia, associated with geometric and mechanical bone
      impairment. Interestingly, we also found a comparable deficit of trabecular bone,
      which may be related to the very high PTH levels. Generalized cortical thinning,
      intracortical porosity and cortical-endosteal resorption ("trabecularization" of
      the cortical bone) are major determinants of reduced bone strength, which may be
      quantitated by pQCT.

PMID- 19379352
TI  - Efficacy of tissue plasminogen activator for thrombolysis in central venous
      dialysis catheters.
AB  - BACKGROUND: Low blood flow is a frequent complication of central-vein (CV)
      dialysis catheters. Since thrombotic occlusion accounts for many cases of reduced
      blood flow, it is common practice to administer empiric thrombolytic therapy in
      an attempt to restore catheter patency and improve function. METHODS: We prepared
      tissue plasminogen activator (tPA) from 50 mg lyophilized powder, which was
      diluted (1 mg/mL) in sterile water for injection. A volume of 1 mL was frozen in
      3 cc polystyrene syringes at -20 degrees C and thawed at room temperature when
      needed. tPA was then administered into the arterial and venous ports of the
      central venous catheter in a volume equal to the manufacturer's stated luminal
      volume and was allowed to dwell for 30 minutes. RESULTS: tPA was administered 62
      times in 25 patients with 30 catheters (11 Tesio, 17 PermCath, 2 Shiley) for
      treatment of low blood flow (pump speed < 250 mL/min). Complete restoration of
      patency was achieved in 23 episodes (mean blood flow pre-tPA 130 mL/min; post-tPA
      320 mL/min); partial restoration of patency was achieved in 20 episodes (mean
      blood flow pre-tPA 69 mL/min; post-tPA 233 mL/min). tPA was just as likely to be
      effective in patients with complete catheter occlusion (i.e., no blood flow) as
      it was when some initial blood flow was present. Nineteen episodes failed to
      respond to tPA. These episodes occurred in 13 catheters, 12 of which ultimately
      underwent radiologic evaluation; an extraluminal cause for low blood flow was
      found in all 12 catheters (6 malpositioned, 6 fibrin sheaths). CONCLUSIONS: tPA
      at a dose of 1 mg/mL is effective for restoring patency in CV dialysis catheters.
      Failure to respond to tPA strongly suggests an extraluminal cause of catheter
      malfunction.

PMID- 19379353
TI  - Extracellular volume changes and blood pressure levels in hemodialysis patients.
AB  - BACKGROUND: Despite the use of highly efficient antihypertensive drugs (AHD),
      blood pressure (BP) is poorly controlled in the vast majority of hemodialysis
      (HD) patients. Many of them show no reduction in nocturnal BP, a finding that is
      associated with left ventricular hypertrophy. The aim of the study was to
      investigate the effect of the removal of a fluid overload on BP by monitoring the
      ambulatory BP during 48 hours in 16 hypertensive HD patients treated with AHD.
      Our aim was to obtain a gradual reduction in post-HD body weight (BW) over a
      period of 3 to 4 months. METHODS: During a period of 3-4 months, the postdialysis
      BW was reduced as the minimal tolerable BW was gradually achieved by slightly
      increasing the ultrafiltration volume. The Na concentration in the dialysate was
      reduced from 143-141 mmol/L to 139-138 mmol/L. Extracellular volume (ECV) was
      measured with a multiple-frequency bioimpedance analyzer (Xitron 4000B, Xitron
      Technologies Inc., San Diego, CA, USA). Based on the change in ECV, the patients
      were subdivided into two groups: group 1 with a reduction in ECV (n = 10), and
      group 2 with no reduction (n = 6). At the start of the study, BW, BP, and AHD in
      group 1 and group 2 were virtually identical. RESULTS: Group 1 showed a
      significant reduction during the entire 48-hour period in systolic (156 +/- 16
      mmHg vs. 140 +/- 14 mmHg, P = 0.030) and diastolic BP (97 +/- 12 mmHg vs. 87 +/-
      9 mmHg, P = 0.026) as well as in mean arterial pressure (MAP, 117 +/- 13 vs. 105
      +/- 10 mmHg, P = 0.027). This reduction was more marked during the night
      (systolic BP 156 +/- 15 mmHg vs. 138 +/- 14 mmHg, P = 0.007; diastolic BP 97 +/-
      12 mmHg vs. 85 +/- 9 mmHg, P = 0.009) than during the day (157 +/- 18 mmHg vs.
      142 +/- 15 mmHg, P = 0.067; diastolic BP 97 +/- 13 mmHg vs. 90 +/- 9 mmHg, P =
      0.126). A significant reduction in systolic load also occurred during the entire
      48-hour period (76 +/- 24% vs. 46 +/- 28%, P = 0.043) as well as in night
      systolic load (75 +/- 21% vs. 41 +/- 30%, P = 0.015) and night diastolic load (67
      +/- 32% vs. 39 +/- 31%, P = 0.030). AHD were stopped in eight and reduced in two
      patients. There were no significant reductions in BP and AHD in group 2.
      CONCLUSIONS: The removal of excess fluid is necessary for adequate BP control and
      especially for the reduction in elevated BP during the night.

PMID- 19379354
TI  - Predicting acute renal failure after cardiac surgery: validation and re
      definition of a risk-stratification algorithm.
AB  - BACKGROUND: Acute renal failure (ARF) after cardiac surgery is associated with
      significant morbidity and mortality, irrespective of the need for dialysis.
      Previous studies have attempted to identify predictors of ARF and develop risk
      stratification algorithms. This study aims to validate the algorithm in an
      independent cohort of patients that includes a significant proportion of female
      and black patients and compares two different definitions of renal outcome.
      METHODS: A large single center cardiac surgery database was examined (n, 24,660;
      1993-2000) which included 29.9% females and 3.7% black patients. Post-operative
      ARF was defined as: a) ARF requiring dialysis, b) > 50% reduction in creatinine
      clearance relative to baseline or requiring dialysis. Clinical variables related
      to baseline renal function and cardiovascular disease were used in recursive
      partitioning analysis for both outcome definitions. Chi-square goodness of fit
      analysis was performed to validate the algorithm. RESULTS: The frequency of post
      operative ARF requiring dialysis ranged between 0.5 and 15.5% based on the risk
      categories with the area under the receiver operating characteristic (ROC) curve
      of 0.78. Using the more inclusive definition of ARF, the frequency was
      significantly higher ranging from 2.6 to 25%(P < 0.001) with an area under ROC
      curve of 0.65. CONCLUSIONS: The renal risk stratification algorithm is valid in
      predicting post-operative ARF in an independent cohort of patients, well
      represented by differences in gender and race. Since the need for dialysis
      remains subjective, a more objective and inclusive definition of ARF may help in
      identifying a larger number of patients 'at-risk'.

PMID- 19379355
TI  - Phosphorus-enriched hemodialysates: formulations and clinical use.
AB  - Although hyperphosphatemia is a cardinal feature of renal failure, the occasional
      patient suffering from end-stage renal disease (ESRD) may present with
      hypophosphatemia. For example, hypophosphatemia can develop in ESRD patients if
      they suffer from malnutrition or if they are aggressively dialyzed.
      Hypophosphatemia is commonly prevented or treated with the oral or the
      intravenous administration of soluble phosphate salts; however, determination of
      the required oral or intravenous dose is difficult. Under appropriate
      circumstances, phosphorus-enriched dialysates can also be employed for the
      purpose of phosphorus administration. Various preparations of soluble phosphate
      salts can be used to enrich hemodialysates.

PMID- 19379356
TI  - An overview of uremic toxicity.
AB  - About 100 uremic retention solutes have been identified at present, but not all
      of these compounds are necessarily toxic. They can be defined as uremic toxins if
      they exert biochemical/biological actions. Based on their physicochemical
      characteristics, there are three major groups of uremic retention solutes: 1) the
      small water-soluble compounds (<500 Da), which are easily removed by standard low
      pore-size dialyzer membranes; 2) the protein-bound solutes (also mostly <500 Da),
      whose dialytic removal is hampered by their protein binding, irrespective of the
      membrane type; and 3) the so-called middle molecules (>500 Da), which can be
      removed only by membranes with a large pore size and/or adsorptive capacity. In
      the present review, we will summarize the currently known information about the
      toxicity of the uremic retention solutes. Although removal of small water-soluble
      urea has been recognized for many years as a current measure of dialysis
      adequacy, data on its toxicity are very scanty. Almost 50 other water-soluble
      compounds are known to be retained in uremia, but only a few exert biological
      effects. Most of the toxic water-soluble moieties, such as the guanidines,
      phosphate, xanthine, and hypoxanthine show an intra-dialytic compartmental
      behavior, which is different from urea. A substantial number of uremic solutes
      are protein bound, and most of them exert biological action. Among them are the
      phenols, indoles, homocysteine, and carboxy-methyl-propyl-furanpropionic acid.
      Recent data suggest that protein binding acts as a buffer against the toxic
      effects of these compounds, and that hypoalbuminemia increases both their free
      fraction and their toxicity. In addition, many middle molecules, such as ss(2)
      microglobulin, leptin, and advanced glycation end products, have been related to
      biological/clinical effects. Our current knowledge of the biological impact of
      the middle molecules is very likely incomplete. It is concluded that many of the
      water-soluble compounds exert little or no toxicity, and that urea removal
      pattern per se is not identical to that of many biologically active molecules.
      Hence, in dialysis, more than urea removal alone should be pursued.

PMID- 19379357
TI  - Uremic toxins: removal with different therapies.
AB  - A convenient way to classify uremic solutes is to subdivide them according to the
      physicochemical characteristics influencing their dialytic removal into small
      water-soluble compounds (<500 Da), protein-bound compounds, and middle molecules
      (>500 Da). The prototype of small water-soluble solutes remains urea although the
      proof of its toxicity is scanty. Only a few other water-soluble compounds exert
      toxicity (e.g., the guanidines, the purines), but most of these are characterized
      by an intra-dialytic behavior, which is different from that of urea. In addition,
      the protein-bound compounds and the middle molecules behave in a different way
      from urea, due to their protein binding and their molecular weights,
      respectively. Because of these specific removal patterns, it is suggested that
      new approaches of influencing uremic solute concentration should be explored,
      such as specific adsorptive systems, alternative dialytic timeframes, removal by
      intestinal adsorption, modification of toxin, or general metabolism by drug
      administration. Middle molecule removal has been improved by the introduction of
      large pore, high-flux membranes, but this approach seems to have come close to
      its maximal removal capacity, whereas multicompartmental behavior might become an
      additional factor hampering attempts to decrease toxin concentration. Hence,
      further enhancement of uremic toxin removal should be pursued by the introduction
      of alternative concepts of elimination.

PMID- 19379358
TI  - Anticoagulation options for pediatric hemodialysis.
AB  - Blood coagulation in the extracorporeal hemodialysis circuit is one of the
      manifestations of bio-incompatibility that is related to the activation of
      monocytes, platelets, and the coagulation cascades. Compared to adults, in
      pediatric patients, the surface area of the extracorporeal circuit is increased
      relative to blood volume. This is due to the patient's smaller blood volume and
      the combination of the higher relative surface area of the dialyzer, smaller
      lumen lines, and small-bore vascular catheters, potentially increasing contact
      activation of coagulation proteins, platelets, and inflammatory cells. Although
      unfractionated heparin remains the most commonly used anticoagulant, low
      molecular weight heparin offers the advantages of a single bolus, less fibrin and
      platelet deposition in the dialyzer, and perhaps more importantly, less
      osteoporosis, hyperkalemia, and abnormal lipoprotein profile. Although regional
      anticoagulants are available, these are often prohibitively expensive or require
      increased complexity of the dialysis procedure (e.g., citrate), but have the
      advantage of reducing the risk of bleeding when compared to heparin. Thrombin
      inhibitors are now available, and with the advent of argatroban, which is
      metabolized in the liver, have become the anticoagulants of choice for the few
      patients who develop heparin-induced thrombocytopenia type II.

PMID- 19379359
TI  - Temperature and thermal balance monitoring and control in dialysis.
AB  - Temperature and thermal balance have been studied in an effort to explain better
      tolerance of ultrafiltration during isolated ultrafiltration and other convective
      techniques as compared to conventional hemodialysis. The large number of
      published studies has led to the conclusion that negative thermal balance of the
      extracorporeal circuit ameliorates hemodynamic stability by increased
      vasoreactivity and increased peripheral resistance. On the other hand,
      measurement of dialysis efficiency (urea removal) did not unequivocally confirm
      the theoretically predicted decrease in efficiency of "cool" dialysis. Another
      suggested application of temperature and thermal balance for assessing
      bioincompatibility is currently hampered by the ability of existing technology to
      evaluate thermal parameters of the extracorporeal circuit only. Publications on
      impact of negative thermal balance of the extracorporeal circuit on
      ultrafiltration-induced changes in blood volume give contradictory results.
      Further studies are needed for elucidation of the impact of thermal balance on
      overall biological response to dialysis.

PMID- 19379361
TI  - Hemodialysis quiz: questions.

PMID- 19379360
TI  - Vascular access in the hemodialysis patient--personal experience and review of
      the literature.
AB  - There is consensus that arteriovenous (AV) fistulae represent the best choice for
      initial vascular access in patients suffering from chronic renal insufficiency
      (CRI) or end-stage renal disease (ESRD) approaching the need of initiating
      hemodialysis therapy. However, this is a challenging task in the rapidly growing
      population of diabetic, aged, and hypertensive patients. The preexisting damage
      of the vascular anatomy and the high cardiovascular comorbidity hinder
      construction of a well functioning arteriovenous fistula. Late referrals to the
      nephrologist delay access surgery and increase the use of temporary and cuffed
      tunneled catheters with all their potential risks. Nevertheless, various
      strategies and tools exist to overcome these problems. Early referral results in
      venous preservation and early selection of side, site, and type of initial
      vascular access. Ultrasound findings are essential components of preoperative
      investigations. Special attention should be paid to the quality of the arteries
      at each section along the forearm, the elbow region, and the upper arm.
      Dedicated, meticulous surgery is mandatory. Fistula monitoring and elective
      revision of the failing AV fistula will result in increasing longevity of the
      blood access, and will reduce morbidity and costs.

PMID- 19379362
TI  - Successful treatment of tuberculous and nocardial arthritis in a hemodialysis
      patient with subsequent kidney transplant.
AB  - A 42-year-old physician on maintenance hemodialysis for chronic renal failure
      presented with intermittent fever and arthritis of the right knee. Synovectomy
      specimen of the right knee showed caseating granuloma, consistent with
      tuberculosis, which was successfully treated with a four-drug regimen of anti
      tuberculous therapy. Subsequently, he had a recurrent effusion of the same joint,
      which on aspiration showed nocardial infection. He was treated with a combination
      therapy (sulfamethoxazole-trimethoprim and amoxicillin) for four months. He
      underwent a successful living-related transplant two months later, and was doing
      well on triple immunosuppression one year after transplantation.

PMID- 19379363
TI  - Hemodialysis quiz: answers.

PMID- 19379365
TI  - Revisiting autonomic dysfunction in end-stage renal disease patients.
AB  - BACKGROUND: Autonomic dysfunction is frequent in end-stage renal disease (ESRD)
      patients, but both the relative involvement of the parasympathetic and
      sympathetic branches and the role of antihypertensive drugs in this setting are
      still controversial. The present study addressed these issues employing a battery
      of standard noninvasive cardiovascular autonomic tests. METHODS: Sympathetic (S)
      function was evaluated by responses of both systolic blood pressure (BP) to
      passive tilting and diastolic BP to handgrip; parasympathetic (P) function,
      through the respiratory sinus arrhythmia test and the heart rate response to the
      4-s unloaded exercise test. Additional tests influenced by both branches of the
      autonomic system (P + S) were accomplished by the assessment of heart rate
      response to the Valsalva maneuver, handgrip, and tilting. RESULTS: Studied
      subjects belonged to one of the three groups: ESRD patients not requiring BP
      medications (n = 11; 8 men, 3 women); ESRD patients receiving antihypertensive
      therapy (n = 36; 21 men, 15 women); and apparently healthy controls (n = 15; 10
      men, 5 women). When the variables grouped according to the branch of the
      autonomic nervous system predominantly probed were analyzed, only the frequency
      of impaired sympathetic autonomic responses was higher in ESRD patients not
      receiving BP drugs compared to controls (55 vs. 23%, P = 0.040). In contrast,
      when ESRD patients receiving BP drugs were compared to controls, the differences
      became significant in S, P, and P + S tests (46 vs. 23%, P = 0.045; 22 vs. 3%, P
      = 0.020; and 34 vs. 13%, P = 0.010, respectively). With the criterion of more
      than one positive finding in any of the variables examined for diagnosing
      autonomic dysfunction, the prevalence of autonomic dysfunction was 20% in
      controls, 64% in ESRD patients not receiving BP drugs (P = 0.005 vs. controls),
      and 67% in ESRD patients receiving BP drugs (P = 0.043 vs. controls).
      CONCLUSIONS: ESRD continues to be associated with a high prevalence of autonomic
      dysfunction. ESRD patients receiving BP drugs were found to have detectable
      impairment in the entire autonomic system in contrast to those not receiving BP
      drugs in whom inadequate responses were restricted to the sympathetic branch.

PMID- 19379366
TI  - Hemodynamic and volume changes during hemodialysis.
AB  - BACKGROUND: Volume overload is a factor in the hypertension of hemodialysis (HD)
      patients. Fluid removal is therefore integral to the hemodialysis treatment.
      Fluid removal by hemodialysis ultrafiltration (UF) may cause intradialytic
      hypotension and leg cramps. Understanding blood pressure (BP) and volume changes
      during UF may eliminate intradialytic hypotension and cramps. Studies (S1, S2,
      and S3) were carried out to determine the amount and direction of changes in body
      fluid compartments following UF and to determine the relationships between BP,
      changes in blood volume (DeltaBV), central blood volume (CBV), cardiac output
      (CO), peripheral vascular resistance (PVR) plus total body water (TBW), and intra
      and extracellular fluid volumes (ICF, ECF) in both the whole body and body
      segments (arms, legs, trunk). METHODS: Indicator dilution technology (Transonic)
      was used for CBV, CO, and PVR; hematocrit monitoring (Crit-Line) was used for
      DeltaBV segmental bioimpedance (Xitron) for TBW, ICF, and ECF. RESULTS: S1 (n =
      21) showed UF sufficient to cause DeltaBV of -7% and lead to minor changes (same
      direction) in CBV and CO, and with cessation of UF, vascular refilling was
      preferential to CBV. S2 (n = 20) showed that predialysis HD patients are ECF
      expanded (ECF/ICF ratio = 0.96, controls = 0.74 [P < 0.0001]) and BP correlates
      with ECF (r = 0.47, P = 0.35). UF to cause DeltaBV of -7% was associated with a
      decrease in ECF (P < 0.0001) and BP directly (r = 0.46, P = 0.04) plus DeltaBV
      indirectly (r = -0.5, P = 0.024) correlated with PVR, while CBV and CO were
      maintained. S3 (n = 11) showed that following UF, total-body ECF changes were
      correlated with leg ECF (r = 0.94) and arm ECF (r = 0.72) but not trunk ECF.
      Absolute ECF reduction was greatest from the legs. CONCLUSIONS: Predialysis ECF
      influences BP and UF reduces DeltaBV and ECF, but CBV and BP are conserved by
      increasing PVR. ECF reduction is mainly from the legs, hence may cause cramps.
      Intradialytic hypotension is caused by failure of PVR response.

PMID- 19379367
TI  - Epidemiology and blood flow surveillance of the native arteriovenous fistula: a
      review of the recent literature.
AB  - Vascular access placement is a key management issue for hemodialysis patients.
      Despite being well regarded as the access of first choice, the native
      arteriovenous fistula (AVF) remains underutilized in the United States. The first
      part of this review examines recent epidemiology studies addressing patient
      factors associated with the use of the synthetic arteriovenous graft as opposed
      to the native fistula. Female gender and older age are consistently associated
      with a higher frequency of graft use. Diabetes, peripheral vascular disease, and
      body mass index were associated with graft use in some but not all of the
      studies. Recent evidence also suggests an independent survival advantage for
      patients dialyzing via native fistulae especially for infection-related
      mortality. The second part reviews evidence surrounding the recommendations for
      blood flow surveillance of the native fistula. The hemodynamic features of the
      native fistula are examined and differences from synthetic grafts are
      highlighted. Clinical studies assessing the use of blood flow surveillance to
      prevent the sudden thrombosis of native fistulae are reviewed. Blood flow
      thresholds for further investigation are yet to be determined definitely for AVF
      and randomized studies should be performed to assesses the impact on AVF
      thrombosis rates.

PMID- 19379368
TI  - Iron management in hemodialysis patients: optimizing outcomes in Vicenza, Italy.
AB  - The management of anemia in uremic patients undergoing hemodialysis requires the
      appropriate combination of erythropoietin treatment, iron supplementation, and on
      occasion androgen therapy. Identifying and correcting functional iron deficiency
      is crucial to optimizing erythropoietin efficiency. Recently, however, the trend
      to administer maintenance iron with resultant high serum ferritin and high
      transferrin saturation has led to an increase in reports of iron overload. Oral
      iron supplementation is inexpensive and safe, but poor patient compliance and
      reduced intestinal absorption may limit its efficacy. Intravenous iron, on the
      other hand, is effective, and its safety is related to the iron salt used.
      Currently available data suggest that iron saccharate may be the safest iron salt
      available for intravenous administration, although iron gluconate is safer than
      the dextran forms of intravenous iron. It should be kept in mind, however, that
      all forms of intravenous iron may have the potential of inducing iron overload.
      At this time, the levels of ferritin that define iron overload are not clearly
      established. The side effects of iron overload are well recognized (infections,
      malignancies, vascular diseases); however, no guidelines exist for safe practice.
      There are many markers of iron deficiency, with serum ferritin and hypochromic
      red cell percentage currently the best markers available in clinical practice.

PMID- 19379369
TI  - Cardiovasoactive peptides in hemodialysis patients: diagnostic tools and
      predictors of outcome: a review of present knowledge and future directions.
AB  - The main cardiovasoactive peptides involved in cardiovascular adaptation to renal
      failure and dialysis are reviewed with a special focus on their possible role in
      pathophysiology, diagnosis of cardiovascular and fluid volume abnormalities, and
      prognostic information. The role of vasoactive peptides in cardiovascular
      stability during hemodialysis (HD) are best seen in sequential HD, where the
      release of vasoconstrictors is stimulated by volume reduction during
      ultrafiltration, but is blunted during isovolemic HD, whereas plasma vasodilators
      increase. Plasma levels of the natriuretic peptides atrial natriuretic peptide
      (ANP) and brain natriuretic peptide (BNP) are elevated in fluid volume overload
      and heart failure and decrease during dialysis. Neuropeptide Y (NPY) is elevated
      in severe volume overload and hypertension and calcitonin gene-related peptide in
      large-volume overload. Plasma BNP increases with left ventricular failure and
      improves during dialysis. Activation of the sympathetic nervous system as
      reflected by increased plasma levels of NPY is associated with poor prognosis.
      High levels of the natriuretic peptides ANP and BNP are likewise predictors of
      poor prognosis. Determinations of plasma levels of cardiovasoactive peptides may
      be helpful in clinical practice to diagnose volume overload and heart failure and
      to assess the severity of heart failure and of hypertension, as a guide to the
      choice of dialysis treatment and pharmacotherapy and to monitor treatment.
      Clinical studies will be needed in HD patients to establish the value of
      measurement of plasma cardiovasoactive peptides in clinical practice. The
      research in this field is still in its infancy and promises to be exciting in the
      future. There appears to be a balance of vasomotor tone and cardiac response to
      meet any emergency and stress such as intermittent dialysis. Further knowledge
      will increase our chances for major therapeutic interventions.

PMID- 19379370
TI  - Physiologic inhibitors of coagulation in patients on chronic hemodialysis.
AB  - Patients on hemodialysis are at increased risk for bleeding and thromboses. The
      intriguing balance between these risks is more complex than once thought, as
      endogenous clotting factors and their regulators come into contact with
      bioincompatible dialyzer membranes, in the setting of an extracorporeal circuit
      of blood flow, in the face of the uremic state. In this review, we summarize the
      current data on the interaction between the physiologic inhibitors of coagulation
      and hemodialysis. Data sources and study selection were obtained from research
      and review articles related to the endogenous anticoagulation pathway published
      in English on MEDLINE from 1972 to 2002. While protein C activity and protein S
      antigen concentrations are increased, there is no change in antithrombin III
      levels during hemodialysis in relation to predialysis levels. Plasma protein Z,
      which has only recently been studied in uremic subjects, is increased as well. In
      addition, hemodialysis leads to elevated tissue factor plasminogen inhibitor,
      thrombomodulin, tissue plasminogen activator, and plasminogen activator inhibitor
      1 activities. The potential functional significance of these observations is
      discussed. Finally, as erythropoietin is commonly prescribed to uremic patients
      and is recognized to be prothrombotic, an appraisal of its interaction with the
      naturally occurring anticoagulants is presented. It is apparent that we are only
      beginning to realize the complexity of the interplay between this myriad of serum
      factors and hemodialysis. Further research is needed to shed light on this
      underexplored area of hemodialysis.

PMID- 19379371
TI  - The practice of dialysis in the developing countries.
AB  - There are few organized data on the practice of dialysis in developing countries,
      mostly because of a lack of renal registries. The economic, human, and technical
      resources required for long-term dialysis make it a major economical and
      political challenge. Most countries do not have not well-formed policies for
      treatment of end-stage renal disease. The dialysis facilities are grossly
      inadequate, and there are no reimbursement schemes to fund long-term dialysis.
      Hemodialysis units are mostly in the private sector and consist of small numbers
      of refurbished machines. Water treatment is frequently suboptimal, and this
      problem has led to a number of complications. Hepatitis B and C infections are
      widespread in dialysis units. Continuous ambulatory peritoneal dialysis (CAPD)
      seems to be the ideal dialysis option for patients living in remote areas, but
      high costs preclude its widespread usage. The Mexican experience suggests that
      even after it becomes affordable, CAPD needs to be used judiciously. Inadequate
      dialysis, infections, and malnutrition account for the high mortality among the
      dialysis population in developing countries. Acute peritoneal dialysis using
      rigid stylet-based catheters is the main form of dialysis in remote areas.
      Pediatric dialysis units are almost nonexistent. A significant lack of resources
      exists in developing countries, making the provision of highly technical and
      expensive care like dialysis a challenge.

PMID- 19379372
TI  - Management of the surgical patient with end-stage renal disease.
AB  - For health providers guiding the end-stage renal disease patient's care,
      conventional surgical and anesthetic principles may demand substantial
      modifications to optimize both the immediate outcome and long-term survival.
      Elective operation is conducted in the setting of optimized acid/base balance,
      volume status and potassium management with pre-operative dialysis completed
      within 24 hours of the procedure (either hemodialysis or peritoneal dialysis).
      When peripheral intravenous access is inadequate, central venous access is
      obtained preferentially through the internal jugular veins because of the
      catastrophic consequences of catheter-induced subclavian stenosis. Infectious
      prophylaxis incorporates antibiotic selection considering the lack of native
      renal drug clearance, the potential for drug loss across dialysis membranes and
      potential interactions with immunosuppressive medications. Judicious
      intraoperative blood and fluid replacement should not be so restricted as to
      permit inadequate end organ perfusion, even if post-operative dialysis is
      necessitated. Hemostasis may be facilitated by the use of desmopressin to correct
      uremic platelet dysfunction. Wound closure techniques should accommodate the
      delayed healing associated with kidney failure and/or iatrogenic
      immunosuppression.

PMID- 19379373
TI  - Extracorporeal support for patients with hepatic failure.
AB  - Extracorporeal support has been advocated for patients with acute and chronic
      liver failure. Patients with acute liver failure and those with decompensated
      cirrhosis can be broadly divided into two groups. The first group comprises those
      with acute liver failure and ongoing hepatic necrosis, and the second, those with
      long-standing chronic decompensation admitted with one or more complications of
      liver failure, such as encephalopathy without any evidence of a precipitating
      factor or accompanying acute deterioration of liver function. This second group
      includes patients with acute liver failure, where the insult causing hepatic
      necrosis has been resolved, and those patients with chronic decompensation who
      suffer another insult to the liver, such as acute infection or variceal
      hemorrhage that causes further liver injury in the setting of multiorgan failure.
      These two groups are likely to have different outcomes and may need to be managed
      differently. In the first group, liver transplantation is the only possible long
      term therapeutic option, whereas in the second group, other possibilities such as
      extracorporeal liver support systems and/or medical therapy may allow these
      patients to return to their previous state before the acute insult. Over time
      extracorporeal support has expanded from simple peritoneal dialysis and
      hemodialysis, to the development of circuits designed primarily to remove both
      water and lipid-soluble toxins and, in addition, bioartificial devices to provide
      replacement synthetic hepatic function. Because many of the patients with an
      acute liver insult have ongoing chronic liver disease and develop hepatorenal
      syndrome, this group of patients has been targeted by several groups to study the
      role of liver support systems.

PMID- 19379374
TI  - Preface.

PMID- 19379377
TI  - Nocturnal hemodialysis in australia.
AB  - BACKGROUND: Because home hemodialysis has long been a common Australian support
      modality, the advent of home-based nocturnal hemodialysis (NHD) in Canada
      stimulated the extension of our existing home- and satellite-based conventional
      hemodialysis (CHD) programs to NHD. As a result, the first government-funded,
      home-based, 6-nights-per-week NHD program in Australia began in July 2001.
      METHODS: Sixteen patients have been trained for NHD; 13 dialyzed at home 8 to 9
      hr per night for 6 nights per week, whereas 3 preferred to train for NHD at home
      using an 8- to 9-hr alternate-night regime. RESULTS: The program experience to
      March 1, 2003, was 655 patient-weeks. Two patients had withdrawn for
      transplantation and 2 for social reasons, although 1 continues on alternate-night
      NHD. There hade been no deaths. Ten patients had dialyzed without partners. All
      patients ceased phosphate binders at entry. Thirteen of 16 discontinued all
      antihypertensive drugs. There were no fluid or dietary restrictions. Phosphate
      was added to the dialysate to prevent hypophosphatemia. Pre- and postdialysis
      urea and phosphate levels were broadly within the normal ranges. All patients
      reported restorative sleep; similarly partners reported stable sleep patterns and
      noted improved mood, cognitive function, and marital relationships in their NHD
      partners. Preliminary cost analyses show that whereas consumables had doubled,
      and epoetin and iron expenditures had risen by 28.9%, other pharmaceutical costs
      had fallen by 47%, and nursing wage costs were 48% of the notional cost had these
      patients remained on CHD. Three patients on NHD were retired, 7 worked full-time,
      3 worked part-time, and 3 drew disability support, whereas previously on CHD, 3
      were retired, 3 had worked full-time, 3 had worked part-time, and 7 had drawn
      disability support. CONCLUSION: We believe that NHD is viable, safe, effective,
      and well accepted with significant lifestyle benefits and reemployment outcomes.
      Although initial setup costs are significant, NHD cost advantage over CHD
      progressively accrues as program numbers exceed 12 to 15 patients.

PMID- 19379378
TI  - Intensive in-center hemodialysis for children: a case for longer dialysis
      duration.
AB  - BACKGROUND: Children with renal failure need their dialysis time optimized.
      Although traditional surrogate markers of outcome in pediatric patients have been
      growth and development, increasing attention is being focused on cardiovascular
      risk factors, such as hypertension, volume overload, malnutrition, and elevated
      calcium (Ca) and phosphorus (P) levels. We have previously shown catch-up growth
      without growth hormone, in children undergoing long intermittent hemodialysis.
      Recently we analyzed retrospectively cardiovascular risk factors in patients
      treated with this regimen. METHODS: Patients starting dialysis between 1997 and
      2001 and on dialysis at least 6 months were evaluated. Charts were reviewed for
      Ca, P, parathyroid hormone (PTH), albumin, hemoglobin and blood pressure levels,
      Ca intake, blood pressure medications, dialysis time, and clearance and
      ultrafiltration rates. Means were calculated for 6- month intervals, up to 36
      months. RESULTS: Mean equilibrated dialyzer Kt/V(urea)ranged from 1.9 to 2.1, and
      mean weekly dialysis time for oliguric patients varied from 14.8 to 16.3 hr, with
      average hourly ultrafiltration rates from 0.3 to 0.4 L. Mean values for P and Ca
      x P were below 1.8 mM and 4.4 mmol (2)/L(2), respectively. Mean hemoglobin levels
      were 115 to 126 g/L, albumin 39 to 41 g/L, and PTH 156 to 231 pg/mL. Most
      patients had normal predialysis blood pressures. CONCLUSIONS: In this pediatric
      cohort, intensive center hemodialysis was associated with excellent growth,
      nutrition, Ca, P, and anemia control and reasonable blood pressure values. Large
      multicenter studies are needed to better determine optimal dialysis therapy for
      children.

PMID- 19379379
TI  - Hepatitis B virus vaccine response in hemodialysis: baseline patient
      characteristics.
AB  - BACKGROUND: Hepatitis B virus (HBV) vaccination is recommended for all
      individuals with renal failure. Nevertheless, the response rate for this vaccine
      in hemodialysis (HD) patients is low, ranging from 50% to 80%. The goal of this
      study was to determine patient characteristics at the initiation of HD that
      influence HBV vaccine response. METHODS: Patients new to HD in an urban
      population in the United States were retrospectively examined. Analyzed patients
      were HBV antibody and antigen negative and hepatitis C virus antibody negative at
      the start of HD, who received HBV recombinant vaccine. Nonresponse was defined as
      failure to seroconvert (>10 UI/L) after six deltoid intramuscular injections of
      vaccine. Response was defined as a lasting seroconversion (at least two
      consecutive positive titers) with </=6 injections. Demographic, laboratory, and
      kinetic modeling data were examined. RESULTS: A total of 33 nonresponders and 64
      responders were identified. Univariate analysis demonstrated that nonresponders
      were older (59 vs. 51 years), had a higher prevalence of diabetes mellitus (DM)
      (70 vs. 39%), had lower serum albumin levels (3.2 vs. 3.3 g/dL), and had higher
      dry weights (84 vs. 71 kg) than responders at HD start. In addition,
      nonresponders had lower normalized protein catabolic rates (0.74 vs. 0.85
      g/kg/day) and lower (single-pool) spKt/V(urea)values (0.95 vs. 1.19).
      Nonresponders had lower serum creatinine levels than responders, despite the
      greater dry weights. In a multiple logistic analysis model, the presence of DM,
      age >/= 55 years, body weight >/=80 kg, and normalized protein catabolic rate
      </=0.75 g/kg/day were associated with HBV vaccination nonresponse. At the end of
      the vaccination period, nonresponders versus responders continued to have lower
      serum albumin (3.5 vs. 3.8 g/dL) and creatinine levels (7.8 vs. 10.0 mg/dL) and
      spKt/V(urea)(1.27 vs. 1.39). CONCLUSION: Hepatitis B vaccine nonresponders on HD
      are older, are more likely to have DM, are more malnourished, and have lower
      spKt/V(urea) than responders. Nonresponders may also have a different body
      composition with a lower ratio of lean to total body mass.

PMID- 19379380
TI  - Relation between access-related Infection and preinfection serum albumin
      concentration in patients on chronic hemodialysis.
AB  - BACKGROUND: Hemodialysis (HD) access-related infection is a major cause of
      morbidity and mortality in HD patients. We tested whether hypoalbuminemia is a
      risk factor for HD access infection and whether mortality of HD catheter
      infection is affected by removal of the infected catheter. METHODS: We analyzed
      the records of 87 patients on chronic HD who were hospitalized for HD access
      related infection. We obtained data on age, sex, preinfection serum albumin
      level, comorbidities, complications, infecting organism, type of infection, mode
      of management, and mortality. We compared preinfection serum albumin levels in 79
      patients with HD access infection with the serum albumin levels of 198 control
      patients on chronic HD without HD access infection admitted to the hospital
      during the same time for other reasons. In the HD catheter infection subgroup, we
      compared mortalities between patients treated with catheter removal plus
      antibiotics as the primary mode of management and those treated initially with
      antibiotics alone. RESULTS: Preadmission serum albumin level was lower in the HD
      access infection group (2.4 +/- 0.6 g/dL) than in the control group (3.2 +/- 0.6
      g/dL, P < 0.0001). Logistic regression identified preadmission serum albumin
      level as a strong independent predictor of HD access infection. In a logistic
      regression model, with age, sex, HIV status, diabetes, and type of HD vascular
      access (excluding arterovenous fistula) as the covariates, the odds ratio of HD
      access infection was 9.8 (95% confidence interval [CI] 4.9-19.7) for a serum
      albumin level </= 3.0 g/dL (P < 0.0001), 10.4 (95% CI 4.97-21.6) for a serum
      albumin level </= 2.5 g/dL (P < 0.0001), and 28.0 (95% CI 5.8-135.9) for a serum
      albumin level </= 2.0 g/dL (P < 0.0001). Case mortality was 25.0% (4/16) in
      patients with tunneled HD catheter infection initially treated with antibiotics
      alone and 2.8% (2/71) in those treated with catheter removal plus antibiotics at
      the time of presentation (P = 0.0096). CONCLUSION: Hypoalbuminemia is associated
      with increased risk of HD access infection. Treatment of HD access infection with
      antibiotics alone is associated with increased risk of death.

PMID- 19379381
TI  - The air-bubble method of locking central-vein catheters with acidified,
      concentrated sodium chloride as a bactericidal agent: in vitro studies.
AB  - BACKGROUND: Soft, cuffed indwelling catheters are used for hemodialysis access
      and intravenous infusions. The majority of these catheters are removed as a
      result of infection caused by contamination of the catheter hub during the
      connection/disconnection procedures. To prevent clot formation in the lumen,
      these catheters are routinely "locked" with heparin or some other anticoagulant.
      None of the anticoagulants commonly used as locking solutions demonstrates any
      significant bactericidal properties. The primary goal of this study was the
      development of a catheter locking method that retains anticoagulant properties at
      the catheter tip and bactericidal properties at the catheter hub. The second goal
      was to find a solution that possesses excellent bactericidal properties but is
      not detrimental in the event of injection into the patient's blood stream. The
      bactericidal properties of acidified, concentrated saline (ACS) were compared to
      concentrated trisodium citrate and to commonly used bactericidal agents such as
      povidone iodine, sodium hypochlorite, and chlorhexidine. METHODS: In preliminary
      studies, the rate of diffusion of solutes was measured in glass tubes. In another
      set of experiments, the mixing of two solutions (anticoagulant and bactericide)
      separated by an air bubble ("air-bubble method") was observed in stationary and
      moving systems. The final series of studies compared the bactericidal properties
      of ACS to other bactericidal solutions mentioned above. RESULTS: The solutions
      diffused swiftly in the glass tubes, and by the third day, both solutions were
      mixed. The air-bubble method prevented mixing in both stationary and moving
      systems. The bactericidal properties of ACS were superior to all other tested
      solutions. CONCLUSIONS: The proposed method of catheter locking with
      anticoagulant at the catheter tip and ACS at the catheter hub separated by an air
      bubble is a promising technique and clinical studies are warranted.

PMID- 19379382
TI  - Air-bubble method of locking central-vein catheters for prevention of hub
      colonization: a pilot study.
AB  - BACKGROUND: The major source of catheter-associated bacteremia is contamination
      of the catheter hub during connection-disconnection procedures. A new method of
      catheter locking has been developed wherein anticoagulant is injected first,
      followed by a 0.1-mL air bubble and 0.9 mL of bactericidal solution. The
      anticoagulant is then located at the catheter tip and the bactericidal solution
      is located at the catheter hub. The air bubble prevents mixing of the two
      solutions. The bactericidal solution was acidified concentrated saline (ACS). The
      27% saline solution has a pH of 2.0. ACS was chosen because it is theoretically
      harmless if injected in the amount used to lock the catheter lumens. The goals of
      this pilot study were to determine whether the new method of catheter locking is
      easy to perform with available syringes and whether eventual injection of the
      experimental solution is well tolerated. METHODS: Ten patients were randomly
      assigned, either to heparin lock (5 patients, 62 treatments) or air-bubble method
      (5 patients, 56 treatments). In the control group, the catheters were locked with
      heparin, 5000 U/mL. In the experimental group, the catheters were locked with
      heparin, air bubble, and ACS. Altogether, the lumens were overfilled by 0.2 mL.
      RESULTS: Compared to the routine method, the experimental method required a 1- to
      2-min-longer procedure time. There were no errors in proper sequence of
      injections into the lumina. There were no episodes of bacteremia related to hub
      contamination in either group. In the air-bubble group, there was one case of
      bacteremia associated with purulent drainage from the exit and the same organism
      in both cultures. In three instances in each group, the locking solution could
      not be aspirated and was injected without any subjective symptoms or objective
      signs. CONCLUSION: We conclude that the air-bubble method of locking central-vein
      catheters is easy to perform. In three instances of air-bubble and ACS injection,
      there were no adverse effects. A full-scale prospective randomized study is
      feasible and warranted.

PMID- 19379383
TI  - Lipoprotein (a) in chronic renal failure: effect of maintenance hemodialysis.
AB  - BACKGROUND: Coronary artery disease accounts for significant morbidity and
      mortality in patients with chronic kidney disease (CKD). Besides the higher
      prevalence of traditional risk factors, several uremia-related factors may play a
      role in accelerated atherosclerosis, such as elevated levels of lipoprotein (a)
      (Lp(a)). The effect of maintenance hemodialysis (MHD) on Lp(a) levels is not well
      understood. The present work was carried out to study the Lp(a) levels in Stage 4
      and Stage 5 CKD patients as well as the effect of MHD on Lp(a) levels in patients
      with Stage 5 CKD. METHODS: The study subjects included 15 patients with Stage 4
      CKD, 15 patients with Stage 5 CKD, and 15 age- and sex-matched healthy controls.
      Plasma Lp(a) was measured by ELISA in all the subjects at the time of entry into
      the study and after 4 weeks of MHD in patients with Stage 5 CKD. Patients on MHD
      were dialyzed two to three times weekly for 4 hr during each session. RESULTS:
      Mean Lp(a) levels were significantly higher in patients with CKD than in control
      patients. In patients with Stage 4 CKD, the Lp(a) level was 34.0 +/- 19.5 mg/dL,
      whereas in Stage 5 CKD the level was 49.0 +/- 30.9 and in healthy controls it was
      22.2 +/- 16.4. In patients with Stage 5 CKD, 4 weeks of MHD led to a significant
      fall in Lp(a) levels by 23.6% (P < 0.001). CONCLUSIONS: The results of this study
      show that increases in Lp(a) levels start early during the course of CKD and
      become more pronounced with increased severity of disease. Initiation of MHD
      lowers Lp(a) levels and may have a long-term beneficial effect on cardiovascular
      morbidity and mortality.

PMID- 19379384
TI  - Psychological symptoms are greater in caregivers of patients on hemodialysis than
      those of peritoneal dialysis.
AB  - BACKGROUND: The purpose of this study was to evaluate and compare psychosocial
      characteristics in caregiving relatives (caregivers) of hemodialysis (HD) and
      peritoneal dialysis (PD) patients. METHODS: Thirty-three caregivers (17 women, 16
      men) of HD patients, 27 caregivers (11 women, 16 men) of PD patients, and a
      control group of 49 subjects who do not care for family members with chronic
      illness (23 women, 26 men) are included in this study. The brief symptom
      inventory (BSI), social disability schedule (SDS), and brief disability
      questionnaire (BDQ) were used for the psychosocial evaluation. RESULTS: The mean
      age, men-to-women ratios, duration of education, and distribution of marital
      status did not differ significantly among the three groups. In addition, dialysis
      duration and distribution of caregiver type were not different between the HD and
      PD groups. Although the mean global severity index scores of the three groups
      were similar, somatization and depression scores from BSI subitems were greater
      in the HD group than the scores of the PD and control groups. Although the mean
      SDS and BDQ scores were higher in the HD group, the differences did not achieve
      statistical significance. BSI subitems such as somatization, obsession
      compulsion, interpersonal sensitivity, depression, and anxiety were positively
      correlated among themselves. Hostility and somatization were negatively
      correlated with age and education, respectively. Nevertheless, somatization was
      positively correlated with age. Social disability was negatively correlated with
      duration of education. CONCLUSION: Somatization and depression are greater in the
      caregivers of center HD patients compared to PD and control groups. According to
      the findings of this study, we suggest that caregiving family members of dialysis
      patients especially on HD also should be evaluated for psychosocial problems and
      supported as needed. Further studies are needed to explore whether psychosocial
      parameters of caregivers predict outcomes for caregivers and patients.

PMID- 19379385
TI  - Impact of predialysis care on clinical outcomes.
AB  - INTRODUCTION: A structured predialysis multidisciplinary team program is
      beneficial in improving quality of life in patients with end-stage renal disease
      (ESRD). Educating pre-ESRD patients about their disease is vital in their care.
      Patients who can identify signs and symptoms of impending problems can seek help
      and avoid complications that may lead to hospital admissions. Our dialysis center
      offers two predialysis classes in a structured format. The first class is for
      those patients with mild to moderate renal disease, whereas the second class is
      for those with advanced renal disease who are expected to need dialysis in 3 to 6
      months. The patients are followed by a multidisciplinary team once they are
      enrolled in our chronic kidney disease program. METHODS: We retrospectively
      reviewed all the charts of patients who started dialysis at our center between
      1997 and 2000. We identified 68 patients who participated in the predialysis
      education program and 35 patients who did not because of late referral or refusal
      to participate. We compared these two groups over a 100-day period (10 days
      before initial dialysis and 90 days after), for hospitalizations, emergency room
      (ER) visits, and dialysis access placement. Patients' comorbid conditions,
      complications, and length of hospitalizations were extracted from the medical
      records. RESULTS: The 68 patients who completed the predialysis program had an
      average age of 60.3 years, a total of 96 hospital days, and 39 ER visits. Average
      length of hospital stay for these patients was 1.4 days. Three patients (4.4%)
      required placement of temporary catheters for the initial dialysis. Fifty-one
      percent of these patients had diabetes mellitus. The 35 patients of average age
      of 54.9 years who did not go through the program had 347 total hospital days and
      39 ER visits. Average length of hospitalization was 9.9 days. Thirteen patients
      (37%) required temporary catheters for initial dialysis. This group included 16
      patients (45.7%) with diabetes. CONCLUSION: Patients who participated in a
      multidisciplinary predialysis education program had fewer complications, ER
      visits, and hospitalizations. They also had fewer temporary catheter placements,
      shorter hospital stays, and reduced costs associated with initial dialysis.

PMID- 19379386
TI  - The neglect of sodium restriction in dialysis patients: a short review.
AB  - In end-stage renal failure, natriuresis decreases, sodium accumulates, and
      extracellular volume (ECV) excess develops. In 1962, Scribner, reporting about
      the first maintenance hemodialysis (HD) patient, observed that ECV control using
      a low-salt diet and ultrafiltration led to blood pressure (BP) normalization.
      Thus, the concept of dry weight, the ideal postdialysis weight allowing for a
      stable normal BP, was born. Achieving dry weight requires a combination of
      negative diffusive sodium balance, adequate ultrafiltration, and a low-salt diet.
      Unfortunately, the low-salt diet is very often neglected today. In the late
      1960s, BP control was achieved in 90% of HD patients using low-sodium dialysis
      and a low-salt diet. As time passed and HD duration was reduced, there was a
      worsening BP control and subsequent increasing in morbidity and mortality. In
      recent years, interventional studies have examined the effects of reducing sodium
      in dialysate, in diet, or in both. All of them show that low-salt diet is
      essential for BP control in HD. While the healthy population is advised to eat a
      reasonably low-salt diet (5 g of NaCl), the K/DOQI Guidelines and the European
      Best Practice Guidelines surprisingly do not even mention salt restriction. To
      achieve dry weight under the present conditions, with short HD duration and a
      frail population, it is mandatory to reduce the interdialytic weight gain. A low
      salt diet is, more than ever, a necessity.

PMID- 19379387
TI  - Continuous renal replacement therapy for liver disease.
AB  - Continuous renal replacement therapy (CRRT) is becoming the treatment of choice
      for critically ill patients with acute renal failure around the world. In
      particular, CRRT is used for patients with combined liver and acute renal
      failure, because they are often hemodynamically unstable. The question arises as
      to whether the use of CRRT should be extended to those patients with acute and
      chronic liver failure who do not have dialysis-dependent renal failure. CRRT
      could potentially allow some detoxification by removing water-soluble toxins and
      also allow regulation of intravascular volume and correction of sodium and other
      electrolyte and acid-base imbalances. By providing homeostatic control, CCRT
      could potentially help support patients by bridging to liver transplantation and
      managing those who eventually recover with hepatic regeneration.

PMID- 19379388
TI  - Evolution of home hemodialysis monitoring systems.
AB  - Systems for monitoring hemodialysis patients at home have evolved during the past
      30 years. They consist of hardware and software to record dialysis events from
      the home hemodialysis machine and transmit them to a server, which in turn sends
      the data to a remote central monitoring center. Most of the parameters monitored
      are related to machine function and events. At present, the only commonly
      monitored patient vital functions are pulse and blood pressure. The early systems
      used direct telephone lines and modem for telecommunication. The use of Internet
      links reduces the cost of the service and provides fast and safe transmission of
      the data. The actual value of these monitoring systems, the need for additional
      monitoring options, indications for specific groups of patients dialyzing at
      home, and acceptance by patients, physicians, and regulators will require further
      evaluation.

PMID- 19379389
TI  - Unusual marine pathogens causing cellulitis and bacteremia in hemodialysis
      patients: report of two cases and review of the literature.
AB  - Cellulitis in immunocompetent hosts is usually caused by skin organisms and
      responds to oral antibiotics. In immunocompromised hosts, such as end-stage renal
      disease (ESRD) patients, unusual organisms with unpredictable pathogenicity can
      cause infections. We present two cases with isolates that are usually encountered
      in coastal waters. The first case describes a 71-year-old African-American ESRD
      patient who presented with bacteremia secondary to a wound infection after
      exposure to flood waters in a tropical storm. The second case describes a 70-year
      old Caucasian male ESRD patient who developed septic shock after a trivial wound
      inflicted while on a shrimp boat. Both patients were successfully treated with
      appropriate antibiotics and supportive measures. The infective agents in both
      cases belong to the halophilic Vibrio species. The causative agent of cellulitis
      and bacteremia in the first hemodialysis patient was identified as Vibrio
      alginolyticus, a non-lactose-fermenting gram-negative bacillus that is rarely
      isolated from blood. The second patient presented with septic shock owing to
      Vibrio vulnificus, which is a lactose-fermenting bacillus known to produce severe
      localized or systemic illness. In both cases, the common features were ESRD
      related immunocompromised state and exposure to marine environments. These two
      cases of life-threatening cellulitis and bacteremia are presented as examples of
      environmental pathogens common to a marine environment in coastal areas and the
      imperative need of rapid identification and prompt initiation of treatment in
      immunocompromised hosts.

PMID- 19379390
TI  - The debate regarding the reliability of international comparisons of survival on
      dialysis continues.

PMID- 19379393
TI  - "In search of optimal renal replacement therapy" symposium.

PMID- 19379395
TI  - Cannulation of blood vessels for prolonged hemodialysis.

PMID- 19379396
TI  - Blood purification by ultrafiltration and fluid replacement (diafiltration).

PMID- 19379397
TI  - A new automatic coil dialyzer system for 'daily' dialysis.

PMID- 19379398
TI  - The "unphysiology" of dialysis: a major cause of dialysis side effects?

PMID- 19379399
TI  - Effect of long-term increase in the frequency and/or prolongation of dialysis
      duration on certain clinical manifestations and results of laboratory
      investigations in patients with chronic renal failure.
AB  - The effects of dialysis frequency increase by one weekly and prolongation of
      dialysis duration by a mean of 17.5% on certain clinical manifestation and
      results of laboratory investigations were studied in a group of 14 patients
      treated with haemodialyses because of chronic renal failure caused by isolated
      renal diseases. Haemodialyses were carried out using a RSP Travenol artificial
      kidney and Ultra Flo 145 dialysers. The blood flow was always 200 ml/min and the
      flow of dialysing fluid was 500 ml/min. One dialyser was used repeatedly during 3
      weeks in the same patients. After increasing the frequency or duration of
      dialyses the patients were not given transfusions of blood donors. The mean
      length of observation after increasing the frequency of dialyses was 6.4 months
      and after increasing their duration this length was 6.9 months. The change in the
      mode of dialysis had no significant effect on the concentration of urea and
      creatinine before as well as after dialysis. The increase in the frequency of
      dialyses caused a significant rise in the value of haematocrit by nearly 4%, a
      rise in the serum albumin concentration by a mean of 0.45 g/100 ml; a mean rise
      in the velocity of nerve conduction by over 6% of the lower normal range, and a
      mean rise in dry body weight by nearly 3.5 kg. Prolongation of dialysis time
      caused a significant mean rise in the haematorcrit value by over 1% before
      dialysis and in the serum albumin level by a mean of 0.30 g/100 ml. Both, the
      increase in the frequency and in the duration of dialyses caused a fall in the
      arterial blood pressure in hypertensive patients. The very favourable effects of
      increased frequency of dialyses on the clinical state of patients and on
      important laboratory parameters suggests that in near future the basic form of
      treatment of chronic renal failure may be daily short-lasting haemodialysis.

PMID- 19379400
TI  - Physiology in daily hemodialysis in terms of the time average concentration/time
      average deviation concept.
AB  - Quotidian or "daily" hemodialysis (DHD) is practiced in widely differing
      schedules. Yet all those schedules are reported to significantly ameliorate
      clinical outcome of patients. It is, however, not clear what is the actual cause
      of this amelioration. Rational possibilities include increased overall dialysis
      dose and increased weekly time. Conventional mathematical approaches (Kt/V(urea)
      concept, equivalent renal clearance) cannot be used to study those issues because
      they do not consider number of dialysis per week and thus ignore the issue of
      treatment schedule "unphysiology." The time average concentration/time average
      deviation (TAC/TAD) concept may well be used to visualize impact of treatment
      schedule on both plasma urea profile statics (TAC) and dynamics (TAD). The
      concept may further help to stratify studies for elucidation of the key factors
      of clinical outcome improvement seen on DHD. Actual physiologic mechanisms
      responsible for this improvement are to be sought among those with having
      derivative component (i.e., reacting to the rate of a change rather than to the
      magnitude of the change). It should, however, be kept in mind that the TAC/TAD
      concept is able to assess unphysiology of a treatment schedule, not unphysiology
      of a single treatment session.

PMID- 19379401
TI  - Daily (quotidian) nocturnal home hemodialysis: nine years later.
AB  - Daily nocturnal home hemodialysis was developed to satisfy the need for a highly
      effective, smooth, and cost-effective home dialysis therapy. It combines the
      benefits of the following dialysis methods: long, frequent, and home
      hemodialysis. It provides a high dialysis dose for small, as well as large,
      molecules including beta(2)-microglobulin; improves quality if life; and leads to
      control of hyperphosphatemia without the need for phosphate binders, as well as
      dissolution for extraosseous calcifications. Furthermore, it controls blood
      pressure often without medications, is associated with regression of left
      ventricular hypertrophy, improves cardiac function, improves anemia as well as
      nutrition, allows an unrestricted diet, and corrects sleep apnea. Finally, it
      decreases the overall cost of patient care and improves cost utility when
      compared to conventional hemodialysis. The main obstacle to its wider utilization
      is the structure of the current reimbursement system. Along with short daily
      hemodialysis, long intermittent dialysis, and the convective dialysis techniques,
      daily nocturnal hemodialysis promises to improve dialysis outcomes.

PMID- 19379402
TI  - Intensive dialysis and blood pressure control: a review.
AB  - The prevalence of hypertension in hemodialysis (HD) patients has increased over
      the years. In the early days of maintenance HD blood pressure (BP) control was
      achieved in most patients. As sessions were shortened, the prevalence of
      hypertension increased. Yet, in principle, dialysis is able to control
      hypertension. Today, in programs using long HD, most patients are normotensive
      without antihypertensive medication. The same is true for patients on daily
      dialysis, but not for those on short thrice-weekly HD. In all studies reporting
      BP normalization, dry weight is regularly achieved. Why the poor control of
      hypertension now? At first sight the shortened session duration is the culprit.
      This is suggested by several epidemiologic observations and strongly supported by
      a prospective experience of changing the HD schedule (short to long HD or
      conversely) in the same group of patients. Recent studies, however, using strict
      volume control show that BP normalization can be obtained in conventional 3 x 4
      hr/week dialysis with relatively low delivered Kt/V(urea). Therefore, prolonging
      the dialysis time and/or increasing the dialysis dose are not required to achieve
      BP control. Intensive dialysis most probably normalizes BP by getting the
      extracellular volume and the amount of sodium in the body back to normal. It acts
      in conjunction with a moderate dietary sodium restriction and the use of
      reasonably low dialysate sodium. With this approach improved BP control can be
      achieved in the vast majority of HD patients.

PMID- 19379403
TI  - Nightly home hemodialysis: five and one-half years of experience in Lynchburg,
      Virginia.
AB  - BACKGROUND: Lynchburg Nephrology Dialysis Incorporated initiated a nightly home
      hemodialysis (NHHD) program in September 1997. As of April 30, 2003, 40 patients
      had completed training; 28 patients were at home and 2 patients were in training.
      The average age of the patients at the initiation of the home-based therapy was
      50 years, with a range of 23 to 81 years. There have been 24,239 treatments at
      home with a total of 84.86 patient-years on NHHD, the longest patient for 66.7
      months and the shortest for 1 month. METHODS: Patients dialyzed using the
      Fresenius 2008H machine, 6 to 10 hr, 5 to 6 nights per week. Treatment parameters
      included a blood flow rate of 200 to 250 mL/min; a dialysis flow rate of 200 to
      300 mL/min; and a standard dialysis solution with 2.0 mEq/L potassium, 3.0 to 3.5
      mEq/L calcium concentrations, 35 mEq/L HCO(3), and 140 mEq/L sodium. The
      longitudinal data of each patient in the program for 1, 2, 3, 4, and 5 years were
      compared to the same patient's pre-NHHD data. There were 25 patients in the
      program for 1 year, 19 patients for 2 years, 14 patients for 3 years, 6 patients
      for 4 years, and 4 patients for 5 years. RESULTS: Statistically significant
      improvement occurred in all five groups' need for antihypertensive medications
      and phosphate binders, SF36 scores, calcium/phosphorus product, blood pressure,
      number of hospital admissions, and number of days of stay in the hospital. The
      mortality rate was 2.4% deaths per patient-year with a 95% confidence interval of
      0.9% to 9.4%. CONCLUSIONS: In a longitudinal study, NHHD showed significant
      improvements in patient secondary outcomes. The improvement in these secondary
      outcomes was associated with an improvement in mortality rate.

PMID- 19379405
TI  - Hemodialysis abstracts from the 24th annual dialysis conference.

PMID- 19379404
TI  - Blood access in daily hemodialysis.
AB  - Frequent dialyses are sometimes perceived as increasing the risk of blood access
      malfunction and decreased longevity. This review of the literature, however,
      indicates that the failure rates and overall fistula survival appear to be better
      with more frequent dialyses than with routine dialysis frequency, although the
      reasons for this phenomenon are not clear. One of the possible explanations is
      that frequent dialyses are associated with fewer intradialytic hypotensive
      episodes, which are very detrimental to the blood access. Another possible
      explanation is the generally lower blood flow used with more frequent
      hemodialyses, particularly long nocturnal hemodialysis. Finally, a decreased
      clotting tendency and decreased rates of hematoma formation at the puncture sites
      are additional possible explanations. Complication rates with bridge grafts are
      not higher with more frequent compared to routine thrice-weekly hemodialysis
      sessions. No such comparative data are available, however, for central-vein
      catheters. This lack of comparisons seems to stem from the intuitive assumption
      by nephrologists that hemodialyses that are more frequent should not adversely
      impact catheter complication rates and survival. No data at all are available on
      the use of the Dialock(R) hemodialysis system (Biolink Corp., Norwell, MA, USA)
      and LifeSite hemodialysis access system (Vasca, Inc., Tewksbury, MA, USA), two
      newer forms of hybrid access in patients undergoing frequent hemodialyses.
      Current evidence shows that the perceived risk of blood access malfunction and
      decreased longevity when patients undergo more frequent hemodialysis is not
      supported by the current literature.

PMID- 19379407
TI  - Inflammation as a cause of malnutrition, atherosclerotic cardiovascular disease,
      and poor outcome in hemodialysis patients.
AB  - Cardiovascular disease (CVD) remains the major cause of morbidity and mortality
      in end-stage renal disease (ESRD) patients treated by hemodialysis (HD). Although
      traditional risk factors are common in dialysis patients, they may not alone be
      sufficient to account for the unacceptable high prevalence of CVD in this patient
      group. Recent evidence demonstrates that chronic inflammation, a nontraditional
      risk factor that is commonly observed in HD patients, may cause malnutrition and
      progressive atherosclerotic CVD by several pathogenetic mechanisms. The cause(s)
      of inflammation in HD patients is multifactorial and includes both dialysis
      related (such as graft and fistula infections, bioincompatibility, impure
      dialysate, and back-filtration) and dialysis-unrelated factors. Although
      inflammation may reflect underlying CVD, an acute-phase reaction may also be a
      direct cause of vascular injury. Available data suggest that proinflammatory
      cytokines play a central role in the genesis of both malnutrition and CVD in
      ESRD. Thus, it could be speculated that suppression of the vicious cycle of
      malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve
      survival in dialysis patients. As there is not yet any recognized, or even
      proposed, targeted treatment for ESRD patients with chronic inflammation; it
      would be of considerable interest to study the long-term effect of various anti
      inflammatory treatment strategies on nutritional and cardiovascular status as
      well as outcome in these patients.

PMID- 19379409
TI  - The inadequacy of Kt/V(urea): a brief history of time.

PMID- 19379408
TI  - Worsening of soft tissue calcifications in a hemodialysis patient following
      parathyroidectomy.
AB  - Hemodialysis patients with soft tissue calcifications present unique challenges
      to nephrologists who play an integral role in their long-term management.
      Although disorders of soft tissue calcification are rare in the general
      population, calciphylaxis and tumoral calcinosis are encountered in up to 4% of
      the end-stage renal disease population. Although they are both associated with
      the deposition of calcium in the soft tissue, they are distinct entities that
      differ markedly in respect to their clinical presentation, morbidity, and
      mortality. It is therefore exceedingly important that the nephrologist be aware
      of these disorders, be able to recognize them, and be able to differentiate them
      from each other to diagnose and treat patients appropriately. To achieve this it
      is necessary that the nephrologist be familiar with the diagnostic tools and the
      treatment modalities that are available. A case of a patient with soft tissue
      calcifications is presented followed by an overview of these disorders including
      a comparison of the clinical, laboratory, radiologic, and histologic findings, as
      well as treatment.

PMID- 19379410
TI  - Remote monitoring in nocturnal home hemodialysis 2003.
AB  - Over the past several years there has been growth in the number of dialysis units
      performing remote monitoring in nocturnal home hemodialysis, there has been
      growth in the technical options available for remote monitoring, and there have
      been more creative approaches to overcoming previous limitations. This article
      will review this growth and the diverse factors driving the innovations
      internationally.

PMID- 19379411
TI  - Six years' experience with short daily hemodialysis: do the early improvements
      persist in the mid and long term?
AB  - Observational studies from several groups have shown consistent beneficial
      effects in patients treated with short daily hemodialysis (SDHD). The
      cardiovascular and nutritional changes appear during the first few months after
      the initiation of SDHD. An extensive review of 17 patients from a group of 36
      ESRD patients treated for up to 6 years with SDHD was undertaken to compare the
      clinicobiologic results during the initial period of standard hemodialysis (3 x 4
      hr/week) and the short daily hemodialysis period at 1 year (SDHD(1)) and
      subsequent years (SDHD(2)). The statistical analysis of the clinicobiologic data
      clearly shows that the initial favorable results obtained during the first year
      of SDHD do persist in the mid and long term, which shows the more physiologic
      nature of this dialytic approach. The amelioration of left ventricular
      hypertrophy is of particular interest, showing a regression of ventricular
      dilation during the first year followed by a reduction of interventricular septum
      and posterior wall thickness during the subsequent years.

PMID- 19379412
TI  - Ultrapure dialysis fluid: improving conventional and daily dialysis.
AB  - Dialysis fluid of standard quality contains a certain amount of bacteria and
      endotoxin. This has been considered acceptable because the dialysis membrane was
      believed to be a protective barrier to blood. However, improved methods for
      detection of cellular activation have demonstrated that bacterial products in the
      dialysate may stimulate monocytes to produce cytokines with most dialysis
      membranes. Ultrapure dialysis fluid is practically free from bacteria and
      endotoxin (< 0.1 CFU/mL and < 0.03 EU/mL) and can be prepared from standard
      quality dialysis fluid using a single step of controlled ultrafiltration. The
      European guidelines for hemodialysis (HD) set the use of ultrapure dialysis fluid
      as the goal for all dialysis modalities. Several clinical studies report improved
      inflammatory status in HD patients when ultrapure dialysis fluid is used,
      compared with standard-quality dialysate. The benefits include less frequent
      occurrence of carpal tunnel syndrome, lower C-reactive protein values, reduced
      need for erythropoietin, better nutritional status, and even better preservation
      of residual renal function. For patients on daily dialysis, dialysate quality is
      especially important because such patients are often treated at home where
      quality control of incoming water may be less rigorous, and increased treatment
      frequency leads to exposure to larger volumes of dialysis fluid than with
      conventional dialysis. The use of ultrapure dialysis fluid together with low
      complement-activating membranes maximizes the biocompatibility of a dialysis
      treatment, a goal of treatment, although there is a lack of evidence to date
      supporting a beneficial effect on mortality. From a physiologic point of view the
      reduced inflammatory stimulus that can be achieved with ultrapure dialysis fluid
      is highly desirable. In addition, achieving ultrapure dialysis fluid is
      realistic, because today it can be practically and economically prepared using
      modern equipment and applying appropriate microbiologic surveillance techniques.

PMID- 19379413
TI  - Daily dialysis in pregnancy.

PMID- 19379414
TI  - Definitions of dialysis dose suitable for comparison of daily hemodialysis and
      continuous ambulatory peritoneal dialysis to conventional thrice weekly dialysis
      therapy.

PMID- 19379415
TI  - Hemofiltration as a treatment for end-stage renal disease.
AB  - Patients treated for end-stage renal disease (ESRD) have a poorer quality of life
      and a higher mortality rate than patients in the general population. In addition,
      the cost to provide ESRD care is tremendous. Daily hemodialysis programs have
      been associated with improvements in the patient's quality of life, anemia
      management, blood pressure, nutrition, and left ventricular hypertrophy. In
      addition, especially when treated at home, cost savings are possible. Daily
      hemofiltration may offer additional benefits with enhanced middle-molecule
      clearance, improved cardiovascular stability, and perhaps a further reduction in
      cost. Finally, ease of use of the NxStage System One may encourage patients to
      undergo their treatment at home.

PMID- 19379416
TI  - Why thrice weekly dialysis?

PMID- 19379417
TI  - Urea standard Kt/V(urea) for assessing dialysis treatment adequacy.
AB  - Urea standard Kt/V(urea) (stdKt/V(urea)) has been proposed as a dose measure to
      assess the adequacy of dialysis treatments of arbitrary length and frequency. It
      is based on two fundamental assumptions: 1) that clinical outcomes for
      hemodialysis and peritoneal dialysis patients are equivalent and 2) that the
      equivalency of such clinical outcomes is achieved when the mean predialysis blood
      urea nitrogen or urea concentration is identical for both therapies. The
      relationships among urea stdKt/V(urea), equilibrated Kt/V(urea), and single-pool
      Kt/V(urea) are reviewed, and the assumptions required for the validity of urea
      stdKt/V(urea) as a universal dose measure to describe dialysis treatment adequacy
      are discussed. It is proposed that urea stdKt/V(urea) is a dose measure for both
      water-soluble and protein-bound toxin clearances; therefore, this parameter may
      be a practical dose measure for assessing the adequacy of dialysis during
      treatments of arbitrary length and frequency.

PMID- 19379418
TI  - Improving arteriovenous fistula construction: fistula first initiative.

PMID- 19379419
TI  - Exploring the paradoxical relationship of hypertension with mortality in chronic
      hemodialysis.

PMID- 19379420
TI  - Percutaneous ethanol injection treatment of severe hyperparathyroidism in
      maintenance dialysis: risks and benefits.
AB  - Renal hyperparathyroidism is one of the main and serious complications that occur
      in chronic kidney disease and particularly during long-term maintenance dialysis.
      Several recent trials indicate that a high calcium phosphorus product is
      correlated with high cardiovascular morbidity and mortality and poor outcome.
      Thus, it is important to improve the control of hyperparathyroidism in chronic
      renal failure patients. Several methods have been reported for treating severe
      hyperparathyroidism resistant to medical therapy. Total parathyroidectomy and
      transplantation or excision of tumor is considered as the treatment of choice.
      More recently, interventional methods with percutaneous ethanol or calcitriol
      injection have been developed. These latter techniques have been reported as an
      alternative to surgical treatment for patients with high perioperative risk. We
      report the occurrence of laryngeal recurrent nerve palsy, vocal fold paralysis,
      and hemiplegia after a successful injection of ethanol in a left parathyroid
      adenoma in a maintenance hemodialysis patient and discuss the restrictions of the
      procedure and alternative treatments in view of the available studies.

PMID- 19379421
TI  - Serum matrix metalloproteinase-3 in hemodialysis patients with dialysis-related
      amyloidosis.
AB  - BACKGROUND: Matrix metalloproteinase-3 (MMP-3) has been linked to osteoarticular
      destruction in rheumatic arthritis. To investigate the role of MMP-3 in dialysis
      related amyloidosis (DRA), we determined serum MMP-3 in long-term hemodialysis
      (HD) patients with and without clinical manifestations of DRA. METHODS: Thirty
      three subjects (63% female, 3% diabetic) enrolled in the study between September
      2001 and June 2003. All patients underwent standard HD three times per week,
      using high-flux dialyzers. Four patients had active DRA complications (DRA
      patients), whereas the others (n = 29) had no evidence of DRA. We determined
      serum concentrations of MMP-3, C-reactive protein (CRP), beta(2)-microglobulin
      (beta(2)M), and interleukin-6 (IL-6). We also studied the effects of
      hemodiafiltration (HDF) on inflammatory measures by transferring the DRA patients
      from regular HD to predilution HDF. RESULTS: The DRA group had been on dialysis
      significantly longer than the control group. Significant positive correlations
      were observed between MMP-3 and IL-6 (R(2) = 0.5143, p < 0.0001) and MMP-3 and
      CRP (R(2) = 0.6492, p < 0.0001). IL-6 levels increased after a single dialysis
      treatment, but this effect was minimal with predilution HDF (the increment of IL
      6 levels did not exceed 10 pg/mL). Serum MMP-3 levels decreased in parallel with
      the decrease of IL-6. CONCLUSIONS: MMP-3 serum levels increase in accordance with
      clinical manifestations of DRA and elevated circulating levels of IL-6. For the
      evaluation of the pathophysiologic state of DRA, serum MMP-3 may be a useful
      predictor indicative of chronic inflammation and osteoarticular disorders in DRA
      patients.

PMID- 19379422
TI  - Iron storage indices and risk of bacterial infections in hemodialysis patients.
AB  - BACKGROUND: Infection is the second leading cause of death among hemodialysis
      (HD) patients. Because iron overload may be a risk factor for bacterial
      infection, concerns about excessive use of intravenous (IV) iron have arisen. In
      this retrospective analysis, we explored the relationship between target iron
      storage indices, as outlined in the Dialysis Outcomes Quality Initiative (DOQI)
      guidelines, and the incidence of bacterial infections. METHODS: We reviewed the
      charts of 87 HD patients who received their first course of IV iron at our
      dialysis unit between 1997 and 2001. Transferrin saturation (TSAT) rate, ferritin
      level, and other clinical/laboratory measures were recorded at baseline. Patients
      were followed for up to 2 years for the outcomes of bacteremia and bacterial
      pneumonia and censored at death, end-of-study observation, or kidney
      transplantation. Cox proportional hazards regression was used to evaluate the
      relationship of bacterial infections to iron storage indices. RESULTS: Thirty-two
      patients had at least one episode of bacterial infections. In multivariate
      analyses, after adjusting for sex and venous catheter use, iron-replete state
      (ferritin > 100 ng/mL and TSAT > 20%) was associated with a threefold higher risk
      of bacterial infections (95% CI 1.3-6.6; p = 0.01). Although diabetes mellitus
      and lower serum albumin had a nonsignificant trend toward an increased risk of
      bacterial infections, no such relationship was seen with the first 3-month
      cumulative IV iron dose. CONCLUSIONS: This study suggests an increased risk for
      bacterial infections at modest levels of iron stores (ferritin > 100 ng/mL and
      TSAT > 20%) among HD patients initiating IV iron. Large prospective studies are
      needed to confirm these relationships.

PMID- 19379423
TI  - Timely referral to the nephrologist: essential to optimizing patient outcomes.
AB  - Annual mortality on renal replacement therapy is about 10% in Western Europe and
      reaches 20% in the United States. The reasons responsible for this excess
      mortality include among others advanced age, high prevalence of diabetes and
      comorbid conditions, susceptibility to infections, and cancer. An additional
      cause that should be considered is late referral to overall renal care and for
      renal replacement therapy. It has been demonstrated recently that early referral
      may provide many advantages for the patient, such as prevention of organ damage
      secondary to uremia and even delay the onset of end-stage renal disease. These
      benefits prompted numerous recommendations for timely referral, both for dialysis
      and for long-term renal follow-up. Despite available guidelines for nephrology
      referral the current practice is still suboptimal, resulting in delayed
      initiation of dialysis and clinical outcomes that are not ideal. There is an
      urgent need in the renal community to change the current practice of referral.
      Beyond the benefits for patients, society may also expect potential cost
      effectiveness from early renal care.

PMID- 19379424
TI  - A new Bayesian method to forecast and fine tune individual hemodialysis dose.
AB  - BACKGROUND: The most commonly used formulas for hemodialysis dose are based on
      single-pool urea kinetics; i.e., they consider the body as a single compartment
      and use an ad hoc adjustment for postdialysis urea rebound. We present a new urea
      kinetic modeling approach, individualized Bayesian urea kinetic modeling (IBKM),
      which incorporates prior knowledge. This method uses measurements made during
      previous treatments to forecast a patient's postdialysis urea rebound and
      clearance and provides a choice of possible dialysis parameters to achieve a
      desired clearance goal. METHODS: We used data from 18 patients (a total of 38
      hemodialysis sessions) to build the model. All patients had been on thrice-weekly
      hemodialysis for at least 1 year before enrollment, and their dialysis
      prescription remained unchanged during the study period. Recorded variables
      included blood urea nitrogen (BUN) measurements and dialysis prescription
      parameters (dialyzer size, KoA, treatment time, blood and dialysis flow). The
      population distribution of urea kinetic parameters-derived from the 18 patients'
      data-and individual urea kinetic data (i.e., pre- and postdialysis BUN) are used
      in the IBKM method to make individual predictions. RESULTS: Estimates (mean+/-SE)
      of population urea kinetic parameters are generation rate 0.17+/-0.01 mmol/min,
      clearance between extracellular and intracellular compartments 646+/-60 mL/min,
      and total volume of distribution 31.5+/-1.5 L, of which the extracellular volume
      is 36+/-4%. The effective dialysis clearance is estimated to be 9.0+/-1.7%, less
      than the expected dialyzer clearance. IBKM predictions of postdialysis
      equilibrated BUN concentrations are accurate: a root mean squared error of 3.4%
      of the "postrebound" BUN concentration at 30 min, a value in the range of urea
      measurement error itself. CONCLUSIONS: IBKM can estimate not only the urea
      kinetics of an actual hemodialysis, but it can also predict a patient's target
      hemodialysis dose for any desired, flexible hemodialysis treatment. The method
      should prove useful for bedside monitoring, forecasting, and fine tuning of
      hemodialysis dose.

PMID- 19379425
TI  - Erythropoietic agents, iron and hemoglobin--What happens beyond the trial
      setting: observational data from the ANZDATA registry.
AB  - BACKGROUND: The issues surrounding anemia management in patients receiving
      dialysis therapy are complex and widely debated. Although numerous trials have
      been published, clinical practice patterns may differ, particularly in the
      presence of uncertainty about the optimal management of anemia in this setting.
      METHODS: We examined data from the Australia and New Zealand Dialysis and
      Transplant Registry (ANZDATA) regarding use of erythropoietic agents (EA),
      hemoglobin, and ferritin concentrations and transferrin saturation in 8476
      prevalent dialysis patients in Australia and New Zealand during the 6 months
      preceding March 31, 2001. From this cross-sectional survey, we examined the
      distribution of reported hemoglobin concentration, transferrin saturation, and
      ferritin concentration. Among hemodialysis patients, other predictors of
      hemoglobin examined included urea reduction ratio (URR), age, sex, and the
      presence of comorbidities. RESULTS: In Australia, 87% of dialysis patients
      received an EA; in contrast, only 42% of New Zealand patients received an EA.
      Hemoglobin concentrations were significantly higher in Australia, where 16% of
      reported values were <100 g/L, compared to New Zealand where 37% reported values
      were <100 g/L. Transferrin saturation and serum ferritin concentrations were
      significantly correlated, but less strongly among those receiving EA than those
      not receiving these agents. Both transferrin saturation and serum ferritin were
      significantly and independently associated with hemoglobin concentration, as were
      age and sex. The association with ferritin was inverse: higher serum ferritin
      concentrations were associated with lower hemoglobin concentrations. There was
      poor agreement (kappa = 0.15) between categories of low transferrin saturation
      (<20%) and low ferritin concentrations (<200 ng/mL). Among the Australian
      hemodialysis patients, there was no significant variation in Hb between
      categories where reported URR was >/=65%, whereas the group with a reported URR
      <65% had a significantly lower hemoglobin concentration. CONCLUSIONS: There was a
      wide variation in reported hemoglobin concentrations in this population.
      Potential contributing factors include variable patient responsiveness to EA and
      iron, differing regulations in Australia and New Zealand regarding government
      subsidy of EA, and the lack of consensus among physicians regarding hemoglobin
      target values. Although a cross-sectional study cannot directly address the
      predictive value of iron indices for iron deficiency, it appears likely that
      transferrin and ferritin have different relationships with hemoglobin, and
      measurement of both may have greater clinical utility than either parameter
      alone.

PMID- 19379426
TI  - Coronary and aortic calcifications in patients new to dialysis.
AB  - BACKGROUND: Vascular calcification has been associated with all cause and
      cardiovascular mortality in patients with end-stage kidney disease (ESRD).
      Whether vascular calcification is present in persons with advanced chronic kidney
      disease starting dialysis or develops in patients on dialysis is unknown. The
      purpose of this study was to examine the prevalence of vascular and coronary
      calcification in patients new to hemodialysis. METHODS: A total of 129 subjects
      new to dialysis were evaluated using electron beam computed tomography. The
      primary outcome was the presence and extent of coronary artery, aortic, and
      valvular calcification. RESULTS: Forty-three percent of subjects had no
      significant coronary artery calcification (total score </= 30) and 27% had no
      detectable aortic calcification. Thirty-four percent had coronary artery scores
      that placed them above the 90th percentile for age and sex. Coronary artery
      calcification was significantly associated with a history of coronary artery
      disease and atherosclerotic vascular disease (ASVD) whereas aortic calcification
      was significantly associated with ASVD. Age (p < 0.0001), pulse pressure (p =
      0.004), diabetes mellitus (p = 0.009), and a history of smoking (p = 0.026) were
      independently associated with the extent of coronary artery calcification. Age (p
      < 0.0001) and pulse pressure (p = 0.0003) were independently associated with the
      extent of aortic calcification. CONCLUSIONS: A large fraction of patients new to
      hemodialysis had no evidence of coronary artery or aortic calcification. Coupled
      with the extensive vascular calcification reported by others in prevalent
      dialysis patients these findings suggest that dialysis-specific factors
      contribute to calcific vascular disease in ESRD.

PMID- 19379427
TI  - The advanced practice nurse-nephrologist care model: effect on patient outcomes
      and hemodialysis unit team satisfaction.
AB  - The tertiary care nurse practitioner/clinical nurse specialist (NP/CNS) is an
      advanced practice nurse with a relatively new role within the health-care system.
      It is stated that care provided by the NP/CNS is cost-effective and of high
      quality but little research exists to document these outcomes in an acute-care
      setting. The clinical coverage pattern by nephrologists and NP/CNS of a
      hemodialysis unit in a large academic center allowed such a study. Two NP/CNS
      plus a nephrologist followed two of three hemodialysis treatment shifts per day;
      only a nephrologist followed the third shift. The influence of this care pattern
      of patients was examined using a cross-sectional review of outcomes such as
      adequacy of delivered dialysis, anemia management, phosphate control,
      hospitalizations, etc. In addition, the level of satisfaction of the dialysis
      team and perceptions of care delivered with the care models was assessed. The
      care model staff-to-patient-number ratio was similar in both groups (1:27 for
      NP/CNS plus nephrologist; 1:29 for nephrologist alone). Patient demographics were
      similar in both groups but the NP/CNS-nephrologist group had patients with more
      comorbidities. No statistically significant (p < 0.05) differences existed
      between the groups in patient laboratory data, adherence to standards,
      medications, inter- and intradialytic blood pressure, achievement of target
      postdialysis weights, and hospitalizations or emergency room visits.
      Significantly more adjustments were made to target weights and medications and
      more investigations were ordered by the NP/CNS-nephrologist team. Team
      satisfaction and perceptions of care delivery were higher with the NP/CNS
      nephrologist model. It is concluded that the NP/CNS-nephrologist care model may
      increase the efficiency of the care provided by nephrologists to chronic
      hemodialysis patients. The model may also be a solution to the problem of
      providing nephrologic care to an ever-growing hemodialysis population.

PMID- 19379428
TI  - Prevention of hemodialysis-related muscle cramps by intradialytic use of
      sequential compression devices: a report of four cases.
AB  - BACKGROUND: Hemodialysis (HD)-related lower extremity (LE) muscle cramps are a
      common cause of morbidity in end-stage renal disease patients on maintenance HD.
      Numerous pharmacologic and physical measures have been tried with variable
      success rates. METHODS: Sequential compression devices (SCD) improve venous
      return (VR) and are commonly used to prevent LE deep venous thrombosis in
      hospitals. We hypothesized that LE cramps are triggered by stagnant venous flow
      during HD and are preventable by improving VR. We prospectively studied four
      adult patients (mean age 61 +/- 14 years) on thrice-weekly HD who experienced two
      or more episodes of LE cramping weekly in the month before the study. SCD were
      applied before each HD on both legs and compressions were intermittently applied
      at 40 mmHg during treatment. RESULTS: All four patients reported complete
      resolution of cramping during the study period that lasted 1 month or 12
      consecutive dialysis treatments. CONCLUSION: Application of SCD to LE may prevent
      the generation of LE HD-related cramping in a select group of patients. Larger,
      controlled studies are needed to establish the utility of this noninvasive
      alternative for the prevention of LE HD-related cramps.

PMID- 19379429
TI  - Early readmission and length of hospitalization practices in the Dialysis
      Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: Rising hospital care costs have created pressure to shorten hospital
      stays and emphasize outpatient care. This study tests the hypothesis that shorter
      median length of stay (LOS) as a dialysis facility practice is associated with
      higher rates of early readmission. METHODS: Readmission within 30 days of each
      hospitalization was evaluated for participants in the Dialysis Outcomes and
      Practice Patterns Study, an observational study of randomly selected hemodialysis
      patients in the United States (142 facilities, 5095 patients with
      hospitalizations), five European countries (101 facilities, 2281 patients with
      hospitalizations), and Japan (58 facilities, 883 patients with hospitalizations).
      Associations between median facility LOS (estimated from all hospitalizations at
      the facility and interpreted as a dialysis facility practice pattern) and odds of
      readmission were assessed using logistic regression, adjusted for patient
      characteristics and the LOS of each index hospitalization. RESULTS: Risk of
      readmission was directly and significantly associated with LOS of the index
      hospitalization (adjusted odds ratio [AOR] 1.005 per day in median facility LOS,
      p = 0.007) and inversely associated with median facility LOS (AOR = 0.974 per
      day, p = 0.016). This latter association was strongest for US hemodialysis
      centers (AOR = 0.954 per day, p = 0.015). CONCLUSIONS: Dialysis facilities with
      shorter median hospital LOS for their patients have higher odds of readmission,
      particularly in the United States, where there is greater pressure to shorten
      LOS. The determinants and consequences of practices related to hospital LOS for
      hemodialysis patients should be further studied.

PMID- 19379430
TI  - Heparin-induced thrombocytopenia during renal replacement therapy.
AB  - There is increasing awareness that antibodies to heparin/platelet factor 4
      complex can develop in both those with acute renal failure treated with
      continuous forms of renal replacement therapy and, to a lesser extent, regular
      hemodialysis patients. Clinical manifestations include premature clotting of the
      extracorporeal circuit and increased central venous thrombosis with indwelling
      venous dialysis catheters, associated with thrombocytopenia and increased
      platelet activation. Nevertheless, a minority of patients who develop
      heparin/platelet factor 4 antibodies do not have thrombocytopenia or thrombosis.
      When systemic anticoagulation is also required to treat venous thrombosis, then
      synthetic heparinoids or the direct thrombin inhibitors argatroban or recombinant
      hirudins are the agents of choice. Neither the synthetic heparinoids nor hirudin,
      however, are without their own problems, in that a minority of patients may have
      cross-reacting antibodies against the currently available heparinoids, and
      antibodies may similarly develop against recombinant hirudin, in this case
      leading to a potentiation of anticoagulant activity and increased risk of
      hemorrhage.

PMID- 19379435
TI  - Dialysis overdose: fact or reality?

PMID- 19379431
TI  - Diffusion study.

PMID- 19379436
TI  - Early start on continuous hemodialysis therapy improves survival rate in patients
      with acute renal failure following coronary bypass surgery.
AB  - Acute renal failure requiring dialysis therapy after cardiac surgery occurs in 1%
      to 5% of patients; however, the optimal timing for initiation of dialysis therapy
      still remains undetermined. To assess the validity of early start of dialysis
      therapy, we studied the comparative survival between 14 patients who started to
      receive dialysis therapy when urine volume decreased to less than 30 mL/hr and
      another group of 14 patients who waited to begin dialysis therapy until the level
      of urine volume was less than 20 mL/hr for 14 days following coronary bypass
      graft surgery. Twelve of 14 patients who received early intervention survived. In
      contrast, only 2 of 14 patients in the late-dialysis group survived. There was a
      significant difference in survival between the two groups (p < 0.01). There were
      no significant differences between the two groups with respect to age, sex ratio,
      the APACHE (Acute Physiologic and Chronic Health Evaluation) II score, and the
      levels of serum creatinine at the start of dialysis therapy (2.9 +/- 0.2 mg/dL
      vs. 3.1 +/- 0.2 mg/dL), as well as the levels of serum creatinine at admission.
      We propose that the timing of the start for treatment of acute renal failure
      following cardiac surgery should be determined by the decrease of urine volume
      and not the levels of serum creatinine. Early start of dialysis therapy may help
      improve the survival of patients with acute renal failure following cardiac
      surgery.

PMID- 19379437
TI  - Kinetic analysis of daily hemofiltration.
AB  - BACKGROUND: Daily hemofiltration (D-HF) is a new treatment modality that shows
      unique solute removal characteristics and possibly provides a high quality of
      life for patients with end-stage renal disease. We evaluated solute removal
      characteristics of D-HF for five patients by kinetic modeling analysis. METHODS:
      Five patients treated with normal 3 x 4 hr/week hemodialysis (HD) were switched
      to D-HF (6 x 2 hr/week). Ultrafiltration rates (Q(F)) or small-solute clearances
      ranged from 63 to 106 mL/min. All the necessary kinetic parameters were
      determined from patients' physical data and HD portion of the clinical
      measurements. The two-compartment kinetic model predicted the concentration
      changes after switching from normal HD to D-HF. RESULTS: Concentrations of small
      solutes such as urea nitrogen (UN) increased, whereas that of beta(2)
      microglobulin (beta(2)-MG) decreased after switching from normal HD to D-HF in
      all five patients. Predicted solute concentrations and clinical measurements for
      UN and beta(2)-MG were in good agreement with mean error less than 10%. The model
      predicted that Q(F) = 155 mL/min may be necessary for time-averaged concentration
      (TAC) of UN to be unchanged. The model also predicted that the 7 times/week D-HF
      should not increase the pretreatment concentration of UN, expecting even much
      lower beta(2)-MG concentration after switching from normal HD to D-HF.
      CONCLUSION: D-HF is superior to normal HD for removing larger solutes but may
      increase the TAC of small solutes. Seven-day (7 times/week) D-HF may improve the
      solute removal capacity of small solutes.

PMID- 19379438
TI  - Cardiac troponin-I and its prognostic significance in a dialysis population.
AB  - BACKGROUND: The objective was to study the prevalence and specificity of elevated
      levels of cardiac troponin-I (cT-I) in patients on maintenance hemodialysis in
      relation to creatine kinase (CK), the CK-MB fraction, and the ratio CK-MB of
      total CK and to assess its significance for the long-term prognosis in these
      patients, compared to other parameters known to influence the outcome. METHODS:
      Predialysis blood samples were taken from 93 asymptomatic hemodialysis patients
      for cT-I, total CK, the CK-MB fraction, and the ratio of CK-MB to total CK. cT-I
      was measured by a microparticle enzyme immunoassay. The patients were followed
      for 1 year, after which baseline levels of cT-I and age, duration of dialysis,
      and the presence of diabetes mellitus and ischemic heart disease were correlated
      by linear regression analysis with the outcome parameter all-cause mortality.
      RESULTS: None of the patients had a cT-I level higher than the manufacturer's
      indicated cutoff point of 2.0 ng/mL for myocardial infarction, indicating a
      specificity of 100%. Nine of the 93 patients (9.7%) had detectable cT-I levels
      (>0.0 ng/mL). Twelve patients died within 1 year, among which 4 had baseline cT-I
      levels above 0 ng/mL. From the study variables, an elevated baseline cT-I was
      found to be the only factor that significantly correlated with the outcome all
      cause mortality (p = 0.029). CONCLUSIONS: cT-I has a high specificity for the
      diagnosis of myocardial infarction in dialysis patients. Despite the relatively
      low number of positive test results, cT-I was found to be significantly
      correlated with the outcome all-cause mortality at 1 year.

PMID- 19379439
TI  - Thrombotic events and markers of oxidation and inflammation in hemodialysis.
AB  - The goal of this study was to determine whether antioxidant therapy with vitamin
      E would alter the rate of vascular access complications or other macrovascular
      complications in hemodialysis (HD) patients. A secondary goal of the study was to
      explore the relationship between baseline pretreatment markers of oxidative
      stress (the advanced glycation end product pentosidine and basal levels of
      vitamin Ealpha and gamma) and the subsequent development of access failure.
      Thirty-five stable patients treated by HD were recruited for the study. Patients
      were provided with vitamin E (800 IU) or placebo capsules to be taken daily.
      Clinical variables, vascular access function (flow meter access flow
      measurements), and circulating blood markers were obtained initially and every 3
      months throughout the study. Vitamin Ealpha levels rose in treated patients from
      12.7 +/- 4.4 to 25.1 +/- 15.1 microg/mL at 3 months and 28.6 +/- 14.8 microg/mL
      at 6 months. Vitamin Egamma levels fell in treated patients from 3.9 +/- 1.7 to
      2.3 +/- 1.5 microg/mL at 3 months and 1.7 microg/mL at 6 months. Patients who
      subsequently developed repeated thrombotic vascular access events were
      characterized by higher baseline pentosidine content of circulating proteins.
      Patients who developed a myocardial infarction had higher pentosidine, lower
      vitamin Ealpha, and much lower vitamin Egamma than patients who did not develop
      thrombotic events. These findings lead to the speculation that the anti
      inflammatory effects of vitamin Egamma may play a more important role in
      thrombotic vascular events than the antioxidant effects of vitamin Ealpha.
      Additional studies of these interactions are in progress.

PMID- 19379440
TI  - Associations with home hemodialysis modality failure and mortality.
AB  - BACKGROUND: Limited data exist on risk factors for home hemodialysis (HH) failure
      and mortality. We sought to determine whether age, helper status, or ethnicity
      was associated with home dialysis failure or mortality. METHODS: We conducted a
      retrospective cohort study of all prevalent and incident patients from a regional
      dialysis unit who initiated HH training from December 2000 to September 2002.
      Baseline demographics, program entry and exit dates, and mortality were
      ascertained. Characteristics of those more likely to remain in the program were
      assessed using logistic regression; survival was determined using Cox
      proportional hazards models. RESULTS: Of the 1117 patients enrolled for dialysis,
      116 patients were trained in the HH program (6.8%). Of those, 45.7% remained in
      the program, 10.3% received a transplant, 10.3% returned to in-center dialysis,
      1.7% were lost to follow-up, and 31.7% expired. Compared to patients who returned
      to center or received a transplant, patients who remained on HH were more likely
      to be older, to have been on dialysis longer, and to have diabetes as their
      primary renal disease. Ethnicity, sex, or type of helper did not affect home
      program status. Among those who remained in the HH program, those with
      hypertension or other renal diseases had better survival than those with
      diabetes, as did those who had related helpers compared to those with unrelated
      helpers. CONCLUSIONS: Older and younger ages, but not ethnicity, helper status,
      or sex, were associated with home dialysis failure. Diabetes remained an
      independent risk factor for increased mortality. HH remains a viable option for
      many patients.

PMID- 19379441
TI  - Six years of experience with nightly home hemodialysis access.
AB  - BACKGROUND: Lynchburg Nephrology Dialysis Incorporated started its nightly home
      hemodialysis (NHHD) program in September 1997. PURPOSE: The purpose of this study
      was to evaluate episodes of exit-site infections, catheter sepsis, and safety and
      longevity of accesses for patients doing NHHD. METHOD: If internal jugular (IJ)
      catheter was chosen, the patient was started on 2 mg coumadin per day when
      catheter was placed. If catheter malfunctioned, it was blocked with a
      thrombolytic agent and coumadin was adjusted to meet a goal international
      normalized ratio (INR) of 1.5 to 2.25. If the problem persisted, the catheter was
      exchanged. For catheters, a threaded lock cannula (BD InterLink device, BD) was
      used to prevent air emboli and infections and a locking device was used to
      prevent disconnects. If arteriovenous (AV) fistula was used, four buttonholes
      were established using 16-gauge needles. If AV graft was used, patients were
      taught the rope ladder cannulation technique using 16-gauge needles. RESULTS: As
      of September 1, 2003, 45 patients have completed training and have performed
      27,063 treatments at home. Total catheter time at home was 930 months. Total AV
      fistula and AV graft times at home were 190 and 20 months, respectively. Upon
      completion of training, 34 patients were using tunneled IJ catheters, 10 were
      using AV fistulas, and 1 was using an AV graft. The IJ catheter exit-site and
      sepsis infection rates were 0.35 and 0.52 episodes per 1000 patient-days,
      respectively. Mean catheter life was 8.5 months with the longest being 66.7
      months and the shortest being 0.2 months. The AV fistula and graft exit-site and
      sepsis infection rates were 0.16 and 0 episodes per 1000 patient-days,
      respectively. Catheter complications included one episode of disconnect due to
      patient's failure to use the locking device, one episode of central stenosis, and
      one episode of intracranial hemorrhage, due to prolonged INR, with resolution of
      symptoms. CONCLUSION: Data support the fact that tunneled IJ catheters, AV
      fistulas, and AV grafts are effective and safe permanent accesses for patients on
      NHHD.

PMID- 19379442
TI  - The International quotidian hemodialysis registry: rationale and methods.
AB  - The HEMO study has provided evidence that a higher dialysis dose per session does
      not improve survival in conventional three times a week hemodialysis (HD).
      Attention has therefore shifted to HD schedules that vary in frequency and/or
      duration of dialysis. Although observational data favoring the use of frequent
      dialysis are steadily accumulating, compelling evidence supporting its
      superiority is still lacking. Several advances have recently been made with a
      view to put this form of therapy on much more solid footing. Upcoming research
      initiatives including clinical trials of frequent HD and the quotidian HD
      registry will provide a wealth of analytic and descriptive data that will help
      define the role for frequent HD regimens as a therapy for end-stage renal
      disease.

PMID- 19379443
TI  - Peptide-coated vascular grafts: an in vivo study in sheep.
AB  - The data on function and patency of prosthetic vascular grafts in various
      clinical settings are limited. The purpose of this in vivo study was to compare
      the function and patency of P15-coated expanded polytetrafluoroethylene (ePTFE)
      vascular grafts to uncoated ePTFE grafts in sheep. The P15 cell-binding peptide
      was covalently immobilized onto the surface of ePTFE grafts by a novel
      atmospheric plasma coating method. We evaluated the amount of neointimal tissue
      ingrowth present at the arterial and venous sides of the anastomoses and the
      degree of endothelial cell resurfacing of the luminal surface of the graft. Four
      P15-coated grafts and two control grafts were implanted as arteriovenous grafts
      between the femoral artery and vein and the carotid artery and jugular vein in
      two sheep (n = 6). One animal was euthanized after 14 days and the other after 28
      days. The study showed the intimal ingrowth was significantly less. The average
      intimal thickness of P15-coated grafts (658 microm) was approximately two and a
      half times less than that of uncoated samples (1657 microm). The newly formed
      endothelial cell lining was thicker and its coverage was more uniform for P15
      coated grafts compared to the uncoated controls.

PMID- 19379444
TI  - Blood compatibility and filtration characteristics of a newly developed polyester
      polymer alloy membrane.
AB  - BACKGROUND: Many synthetic polymeric membranes have been widely used for blood
      purification therapies for removing larger solutes and for better blood
      compatibility. METHODS: Five different filters with polyester polymer alloy
      (PEPA) membrane (Nikkiso) that included polyvinylpyrrolidone (PVP), that is,
      standard-pore-size FLX (PEPA with PVP(-)), standard-pore-size FDX (PEPA with
      PVP(+)), new FDX (PEPA with PVP(++)), larger-pore-size FDY (PEPA with PVP(+)),
      and new FDY (PEPA with PVP(++)), were evaluated in terms of in vivo blood
      compatibility and aqueous in vitro sieving coefficient (s.c.) for albumin.
      RESULTS: FDY showed excellent small changes in C3a concentration during the
      treatment right after switching from polysulfone membrane, leaving no significant
      changes in other blood-compatible indices. New FDY, in contrast, showed less
      biocompatible characteristics in terms of C3a, which may be caused by increased
      use of PVP. FLX (no PVP) showed the highest s.c. for albumin. With a hydrophilic
      agent (PVP), the s.c. was greatly reduced in FDX. By enlarging the pore diameter
      in FDY, the s.c. increased in accordance with the enlargement. Generally
      speaking, polysulfone filters with PVP(+++) reach the peak s.c. value
      approximately 10 min after starting the experiment. The s.c. of the PEPA membrane
      with no or small amount of PVP, which showed excellent blood compatibility, never
      showed peaks, whereas the peak s.c. values were found in new PEPA with increased
      amount of PVP that showed higher C3a changes. CONCLUSIONS: The separation
      characteristics of aqueous albumin may be related to its blood compatibility.

PMID- 19379445
TI  - The opposing actions of the two parathyroid hormones, 1-84 PTH and 7-84 PTH:
      improvement in renal bone and calcium metabolism management.
AB  - Bone biopsy, while invasive, is the gold standard for assessing bone status.
      According to published bone biopsy studies, half of the end-stage renal disease
      patients have adynamic bone disease. Compared to high-bone-turnover disease,
      adynamic bone disease has the higher mortality and is associated with arterial
      calcification. The treatment for high-bone-turnover disease is divergent from the
      treatment for adynamic bone disease. The parathyroid hormone (PTH) assay has been
      relied on as the routine, noninvasive diagnostic method to assess bone status.
      According to bone biopsy studies, the intact PTH assay has been demonstrated as
      ineffective at differentiating adynamic bone disease from normal and high-bone
      turnover disease. For example, bone biopsy studies found the normal range for
      iPTH to be 451 to 1339 pg/mL and the range for adynamic bone disease to be 400 to
      919 pg/mL. Intact PTH measures the sum of the two PTH hormones 1-84 PTH and 7-84
      PTH. Specific 1-84 PTH assays neglect the role of the 7-84 PTH hormone, which is
      to lower bone turnover. According to independent bone biopsy studies, the 1-84
      PTH/7-84 PTH ratio is 94% accurate in identifying adynamic bone disease and 94%
      accurate in assessing bone-turnover status.

PMID- 19379446
TI  - Convective renal replacement therapies for acute renal failure and end-stage
      renal disease.
AB  - Although hemodialysis remains the primary treatment modality for the management
      of patients with end-stage renal disease (ESRD), its clearance of relatively
      large-sized uremic toxins is limited due to its primarily diffusive nature.
      Moreover, recent studies suggesting conventional, diffusion-based therapies may
      be limited in their ability to influence outcome in ESRD patients indicate the
      need for alternative chronic dialysis approaches, an example of which is
      convective therapies. In an analogous manner, a reassessment of the dialytic
      management of critically ill patients with acute renal failure (ARF) has also
      occurred recently based on clinical evidence that high-dose continuous
      hemofiltration improves survival. These recent clinical results suggest the
      utilization of convective therapies in both ARF and ESRD will increase in the
      future. This article provides a review of convective therapies, with an initial
      discussion of the determinants of convective solute removal. This is followed by
      a comprehensive overview of the manner in which hemofiltration and
      hemodiafiltration are applied clinically.

PMID- 19379447
TI  - Differences in cardiovascular mortality rates among hemodialysis patients in the
      United States and Japan: the importance of background cardiovascular mortality.
AB  - Mortality rates among hemodialysis patients differ greatly among the United
      States, Europe, and Japan and it has been hypothesized that this is mainly due to
      differences in practice patterns. Results from the international DOPPS study,
      however, indicate that differences in practice patterns among the United States,
      Japan, and Europe are small and not alone explanatory for the differences in
      mortality rates. Ethnic variability in predisposition to atherosclerotic
      cardiovascular disease in the general population may lead to significant
      differences in background cardiovascular mortality in the United States, Japan,
      and Europe. It is our hypothesis that cardiovascular mortality in dialysis
      patients is to a great extent dependent on cardiovascular background mortality of
      the general population. We are currently studying the relationship between all
      cause and cardiovascular death rates in countries worldwide using the WHO
      database. Preliminary data from 35 countries show that all-cause and
      cardiovascular death rates differ significantly among regions, with Eastern
      European countries reporting four- to sevenfold higher death rates than Asian
      countries. A strong linear relationship between cardiovascular and all-cause
      death rates is observed among these countries. The next step of our study will be
      to compare country-specific cardiovascular death rates of dialysis populations
      with those of the respective general populations. Ethnic differences in
      cardiovascular morbidity and mortality may be explained by genetic variability
      based upon polymorphism of genes involved in the pathogenesis of atherosclerosis
      and myocardial infarction.

PMID- 19379448
TI  - Cuffed-catheter-related Lemierre syndrome.
AB  - Sepsis is a common problem in patients who have cuffed catheters for
      hemodialysis. Line sepsis, however, has not often been associated with septic
      thrombophlebitis as seen in Lemierre syndrome. Thrombophlebitis of a central vein
      associated with catheter placement is extremely rare and when encountered is
      known to affect the femoral or the subclavian vein. Thrombophlebitis of the
      internal jugular vein after hemodialysis catheter placement has not been
      reported. We present the case of a woman with line sepsis who developed Lemierre
      syndrome, a serious complication of which the medical community should be aware.
      Lemierre syndrome requires a high index of suspicion for diagnosis and can have a
      fatal outcome if not treated with appropriate antibiotics.

PMID- 19379449
TI  - A report on four new cases of nephrogenic fibrosing dermopathy in chronic
      hemodialysis patients.
AB  - Nephrogenic fibrosing dermopathy (NFD) is a rare clinical entity affecting
      patients with renal failure, often on chronic dialysis or after transplantation.
      The patient profile at risk for this debilitating condition is undefined. Lack of
      awareness of the condition has hampered epidemiologic work in identifying the
      etiology. We present four chronic hemodialysis (HD) patients who developed this
      disease. The patients' ages ranged from 26 to 75 years, and they had received HD
      from between 20 months and 10 years before the diagnosis of NFD. Two patients had
      a history of renal transplantation. All patients had progressive thickening and
      woody induration of the skin associated with contractures, leading to difficult
      ambulation, and permanent disability within weeks of the diagnosis. In one case,
      the diaphragm, psoas muscle, and pericardium were involved. The latter is likely
      the first report of pericardial involvement of NFD. In all four patients, the
      skin findings were restricted to the extremities, sparing the trunk and face.
      Skin biopsy findings included thickened dermis with particularly thickened
      collagen bundles, fibroblast proliferation, minimal mucin deposition, and nearly
      absent inflammation. The pathologic findings were distinct from scleromyxedema
      and scleroderma. We found no laboratory evidence of autoimmune disease or thyroid
      dysfunction to account for alternate etiologies. CD34-positive cells were
      documented in the skin biopsies as well as in the diaphragm, psoas muscle, and
      pericardial tissue of the concerned case. NFD is a novel fibrosing disorder of
      progressively debilitating nature which needs further clinical characterization
      and recognition to guide investigation of its pathogenesis.

PMID- 19379451
TI  - Time-dependent changes in B-type natriuretic peptide after heart transplantation:
      correlation with allograft rejection and function.
AB  - Endomyocardial biopsy is the gold standard to diagnose cardiac allograft
      rejection, although a noninvasive modality such as brain natriuretic peptide
      (BNP) is attractive. The authors examined the correlation of BNP levels with
      rejection patterns and allograft function in cardiac allograft recipients
      followed up to 8 years. One hundred forty-four consecutive patients underwent
      endomyocardial biopsy, right heart catheterization, and blood sampling. BNP
      levels decreased during the first 6 months after transplant but then reached a
      plateau. Time-dependent correlations were made between BNP levels and allograft
      rejection, left ventricular ejection fraction, pulmonary capillary wedge
      pressure, right atrial pressure, and serum creatinine. BNP levels were not
      different between patients with any rejection pattern and no rejection prior to
      or after 6 months following transplant. BNP levels did not correlate with
      ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, or
      creatinine in the first 6 months after transplant. Statistically significant
      correlations existed between BNP and these parameters after 6 months following
      transplant. In cardiac transplant recipients, BNP levels decrease in the first 6
      months following transplant and then reach a plateau regardless of the presence,
      type, or severity of allograft rejection. BNP levels do predict allograft
      rejection but correlate with allograft function after 6 months following
      transplant.

PMID- 19379450
TI  - Racial and gender trends in the use of implantable cardioverter-defibrillators
      among Medicare beneficiaries between 1997 and 2003.
AB  - Differences in the use of implantable cardioverter-defibrillators (ICDs) have
      been reported, but the extent to which they have widened after the publication of
      major clinical trials supporting their use is unclear. Using data on Medicare
      beneficiaries, the authors determined annual age-standardized population-based
      utilization rates of ICDs for white men, black men, white women, and black women
      from 1997 to 2003. During the study period, overall use of ICDs increased most
      for white men (81.7-254.7 procedures per 100,000 from 1997 to 2003) and black men
      (38.0-151.7 procedures per 100,000), with white women (28.9-98.4 procedures per
      100,000) and black women (18.2-77.3 procedures per 100,000) showing smaller
      increases in comparison. After adjustment with multivariable regression models,
      differences in utilization rates between whites and men widened compared with
      blacks and women between 1997 and 2003, a period when indications for ICD therapy
      have expanded.

PMID- 19379453
TI  - Prognostic value of natriuretic peptides in Chagas' disease: a head-to-head
      comparison of the 3 natriuretic peptides.
AB  - To determine the diagnostic and prognostic value of natriuretic peptides in
      patients with Chagas' disease (CD), the authors first measured atrial (ANP), B
      type (BNP), and C-type natriuretic peptide (CNP) and compared their diagnostic
      and prognostic capacity with that in other dilated cardiomyopathies (DCM). The CD
      and DCM patients were subdivided according to their New York Heart Association
      (NYHA) classification. Circulating ANP and more pronounced BNP, but not CNP, were
      increased in CD and DCM patients in relation to NYHA class. Importantly, ANP and
      BNP were already significantly elevated in CD patients without systolic
      ventricular dysfunction. All 3 natriuretic peptides were correlated with
      echocardiographic parameters in CD patients. While ANP and BNP have high
      predictive value for mortality and necessity for heart transplant in CD, CNP can
      not predict them. Thus, ANP and BNP rather than CNP could be used as valuable
      molecular markers to identify asymptomatic CD patients for early therapy and
      predict clinical outcomes.

PMID- 19379454
TI  - The impact of smoking status on the health status of heart failure patients.
AB  - Smoking is a major risk factor for the development of heart failure (HF). Yet,
      little is known about smoking's effects on the health status of established HF
      patients. HF patients were recruited from outpatient clinics across North
      America. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was used to assess
      disease-specific health status. Smoking behaviors were classified as never having
      smoked, prior smoker, and as having smoked within the past 30 days. Risk-adjusted
      multivariable regression was used to evaluate the association of smoking status
      with baseline and 1-year KCCQ overall summary scores. Smoking was not associated
      with baseline health status. However, a significant effect was observed on 1-year
      health status among outpatients with HF with current smokers reporting
      significantly lower KCCQ scores than never smokers or ex-smokers. These findings
      highlight an additional adverse consequence of smoking in HF patients not
      previously discussed.

PMID- 19379452
TI  - Effect of aldosterone antagonism on exercise tolerance, Doppler diastolic
      function, and quality of life in older women with diastolic heart failure.
AB  - Optimal therapy for diastolic heart failure (DHF), the most common form of heart
      failure in older persons, is unclear. To determine the effect of aldosterone
      antagonism in DHF, the authors conducted an open-label preliminary trial of
      spironolactone 25 mg/d in 11 women with DHF. Cardiopulmonary exercise testing,
      Doppler echocardiography, and a quality-of-life survey were administered at
      baseline and after 4 months. Peak exercise VO(2) increased by 8.3% (P=.001), the
      ratio of Doppler diastolic early filling velocity to mitral annulus velocity
      decreased by 25% (P=.02), quality-of-life score improved by 21% (P=.16 for
      trend), and median New York Heart Association class improved from class III to
      class II (P=.004). Findings from this preliminary study confirm the role of
      aldosterone in the pathophysiology of DHF and suggest that aldosterone antagonism
      may benefit such patients. These hypotheses are currently being tested in two
      separated National Institutes of Health-funded, randomized trials, the
      Spironolactone for Failure in the Elderly (SPIFFIE) and the Treatment of
      Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)
      trials.

PMID- 19379455
TI  - Anemia in chronic heart failure.
AB  - Anemia is frequently observed in patients with chronic heart failure and is
      increasingly recognized as an important and treatable condition. The present
      review will summarize the current knowledge of the prevalence, causative factors,
      and pathophysiologic correlates of anemia in chronic heart failure. Despite
      increasing knowledge of anemia there are very few evidence-based recommendations
      for treatment. Potential benefits of therapy with supplemental hematinics such as
      iron, subcutaneous erythropoiesis-stimulating agents, or both will also be
      discussed.

PMID- 19379456
TI  - Cardiac manifestations of Fabry's disease: a story of mother and son.

PMID- 19379457
TI  - Critical bilateral renal arterial stenosis presenting as cardio-renal syndrome:
      isolated ultrafiltration preceding percutaneous transluminal revascularization.

PMID- 19379460
TI  - Historical vignettes in heart failure.

PMID- 19379461
TI  - Prevention of diverticulitis.

PMID- 19379463
TI  - Effects of in vitro culture of mouse fetal gonads on subsequent ovarian
      development in vivo and oocyte maturation in vitro.
AB  - Under organ culture, female fetal gonads in mice cannot develop beyond the
      preantral follicle stage unless the follicles are individually isolated and
      cultured again. In this study, we investigated the effect of in vitro culture of
      female fetal gonads before transplantation on subsequent in vivo development. The
      gonads derived from female fetuses 12.5 days postcoitum were organ-cultured for
      0, 7 and 14 days, and then were grafted underneath the kidney capsules of severe
      combined immunodeficient mice and recovered at 21, 14 and 7 days post
      transplantation, respectively. The histological analysis of the grafts showed
      that the in vitro culture of the fetal gonads restricted follicular development
      to the antral follicle stage post-transplantation. In the grafts cultured for 14
      days, particularly, no antral follicle was observed. However, the oocytes in
      these follicles had grown to around 65 microm in diameter and had competence to
      resume meiosis in vitro. When the fetal gonads were grafted after culture for 7
      and 14 days, 13.0% and 6.8% of the oocytes progressed to the metaphase II stage,
      respectively. These data showed significant differences (P < 0.05) in comparison
      with the control group (25.3%). Our results indicate that the in vitro culture of
      female fetal gonads before transplantation affects the subsequent in vivo
      development of both follicular cells and oocytes, and in vitro oocyte maturation.
      However, this effect seems to be more severe in terms of follicular development
      when compared with oocyte growth and maturation.

PMID- 19379464
TI  - Murine double-minute 2 homolog single nucleotide polymorphism 309 and the risk of
      gynecologic cancer.
AB  - A functional T to G germline polymorphism in the promoter region of murine double
      minute 2 homolog single nucleotide polymorphism 309 (MDM2-SNP309) has been
      reported to profoundly accelerate tumor formation, suggesting that it may also
      represent a powerful cancer predisposing allele. In this study, MDM2-SNP309 was
      examined in a total of 400 blood samples from 108 normal, 88 cervical, 119
      endometrial and 85 ovarian cancer cases using two independent polymerase chain
      reaction assays for each allele. When the MDM2-SNP309 genotype was classified
      into two subgroups of TT+TG and GG, the GG genotype was associated with an
      increased risk for the development of endometrial cancer (odds ratio [OR]= 1.91,
      95% confidence interval [CI] = 1.05 to 3.47) compared with the TT+TG genotype (P
      = 0.0353). The G allele also increased the risk of endometrial cancer (OR = 1.20,
      95% CI = 0.83 to 1.74) compared with the T allele, but no statistical difference
      was found (P = 0.3333). The homozygous GG genotype was also associated with
      postmenopausal status and type I endometrial cancer (P = 0.0306 and 0.0326,
      respectively). There was no significant difference in the genotype or allele
      prevalence between control subjects and cervical or ovarian cancer patients.
      These results suggest that homozygous GG genotype of MDM2-SNP309 may be a risk
      factor for postmenopausal and type I endometrial cancer in a Japanese population.

PMID- 19379465
TI  - The world belongs to the brave.

PMID- 19379466
TI  - Perspective on bifurcation PCI.
AB  - Coronary bifurcation lesion is a complex lesion with suboptimal angiographic and
      clinical results. There has been no satisfactory classification of the lesion
      that can guide selection of strategies and predict short- and long-term outcomes.
      The difference between left main (LM) bifurcation lesions and non-LM bifurcation
      is striking. So many stenting strategies have been proposed and tried in trials.
      They include the V, T, Y, one-stent, two-stent, crush, mini-crush, DK, and SKS
      techniques. However, because these techniques are time and labor intensive,
      dedicated bifurcated stents have been invented and trialed in humans. This review
      presents a historical perspective of interventions in bifurcated lesions, with
      the strengths and weaknesses of the major strategies and of the new dedicated
      stents.

PMID- 19379467
TI  - Physiologic evaluation of bifurcation lesions using fractional flow reserve.
AB  - Functional evaluation of bifurcation lesions is more difficult than usual lesions
      due to their complex anatomy. Angiographic and intravascular ultrasound criteria
      for main branch intervention cannot be directly applied to side branch lesions
      due to the difference in underlying lesion characteristics, geometric changes
      during intervention, and the size of myocardial territory. Fractional flow
      reserve is a physiologic parameter which reflects both the degree of stenosis and
      the area of perfusion supplied by a specific coronary artery. The present review
      will focus on using fractional flow reserve in bifurcation lesions.

PMID- 19379468
TI  - Stent thrombosis after percutaneous coronary intervention for bifurcation
      lesions.
AB  - Percutaneous coronary intervention of bifurcation lesions is known to be
      associated with higher risk of complications than non-bifurcation lesions. In the
      drug-eluting stent (DES) era, the risk of stent thrombosis (ST) is of particular
      concern because of its catastrophic consequences and late occurrence. The risk of
      ST in PCI of bifurcation lesions remains low even with the use of a two-stent
      strategy compared with a provisional side branch stenting strategy. Also, the use
      of DES has no higher risk of ST compared with bare metal stents. Prevention of ST
      in PCI of bifurcation lesions remains pivotal and must include appropriate
      duration of dual antiplatelet therapy, meticulous attention to stent deployment
      techniques, and use of intravascular ultrasound for guidance whenever needed.

PMID- 19379469
TI  - Importance of kissing balloon inflation in bifurcation stenting.
AB  - Percutaneous bifurcation intervention is usually sufficient with a single-stent
      strategy. When the double-stent strategy is employed, higher restenosis and
      target lesion revascularization (TLR) rates are observed, especially at the side
      branch ostium. The results may be improved, however, with refinement in
      techniques, for example, final kissing balloon inflation and double kissing
      balloon inflation.

PMID- 19379470
TI  - Twenty-four-month update on double-kissing crush stenting of bifurcation lesions.
AB  - A group of 312 patients who underwent percutaneous coronary intervention for
      bifurcation lesions at 12 centers in China, Singapore, Thailand, Israel, India,
      and Japan were enrolled in a prospective, randomized DKCRUSH-1 trial. The goal of
      the study was to compare the double kissing (DK) crush technique with the
      classical crush stenting technique. This study was carried out to determine the
      differences in the rates of final kissing balloon inflations (FKBI) and the long
      term clinical outcomes. The 8-month results of the DKCRUSH-1 study have been
      previously reported. Here, we present several subgroups analysis and a 24-month
      clinical update. The results confirmed a sustained, lower MACE rate at 24 months
      with the double kissing (DK) crush stenting technique compared with that for the
      classical crush stenting technique (18.1% vs. 29.9%, p = 0.044).

PMID- 19379471
TI  - Benefits and limitations of cypher stent-based bifurcation approaches: in vitro
      evaluation using micro-focus CT scan.
AB  - Intervention for bifurcated lesions is a complex procedure. It could involve a
      simple main vessel stenting to a comprehensive double stenting of the main vessel
      and side branch. The clinical outcomes of these different strategies were
      evidenced by recent results of many randomized trials. However, the mechanisms of
      technical success or failure from these stenting strategies were not
      investigated. In this bench study, in vitro silicone bifurcated vessel models
      were constructed. Stenting from various technical strategies was studied in
      detail by micro-focus computer tomography.

PMID- 19379472
TI  - Examination of stent deformation and gap formation after complex stenting of left
      main coronary artery bifurcations using microfocus computed tomography.
AB  - BACKGROUND: Fluoroscopy and intravascular ultrasound (IVUS) lack sufficient
      resolution for assessing the results of complex stenting in true bifurcation
      lesions. OBJECTIVES: After diverse bifurcation stenting at the left main coronary
      artery (LM) bifurcation model, the results were examined using microfocus
      computed tomography (MFCT). METHODS: The strut distribution of three kinds of
      stents deployed on a straight vessel segment was investigated. Classical crush,
      double kissing (DK)-double crush, and culotte stenting were performed on a three
      dimensional (3D) LM model. The results were assessed using cross-sectional,
      longitudinal, and 3D reconstruction views of MFCT. RESULTS: Nonuniform strut
      distribution was observed in a corrugated stent design deployed on a straight
      vessel segment. Following classical crush stenting, a relatively large gap at the
      nonmyocardial site was observed in the corrugated stents. When the guidewire
      recrossed outside the ostium of the crushed side branch stent, kissing balloon
      inflation caused further crushing of the stent at the more distal segment. The
      dilated strut rose up from the main vessel bed after the first kissing balloon
      inflation in DK crush stenting; the advantage of DK would be cancelled after main
      vessel stenting due to recrushing the raised strut. The culotte stenting with
      closed-cell stents showed the restriction of the expansion at the branch ostium
      when it was dilated with a 3.5-mm balloon. The culotte stenting with open-cell
      based stents showed a good stent apposition except for a tiny gap and small
      metallic carina at the distal bifurcation. CONCLUSION: MFCT analysis in the 3D
      phantom model is useful to assess the structural deformation of the stents and
      gap on vessel wall coverage after complex stenting at the LM bifurcation.

PMID- 19379473
TI  - Novel side branch ostial stent.
AB  - Bifurcation lesions are technically challenging and plagued by a high incidence
      of restenosis, especially at the side branch orifice, which results in a more
      frequent need for revascularization during the follow-up period. This report
      discusses two clinical experiences with a novel side branch ostial stent, the
      BIGUARD stent, designed for the treatment of bifurcation lesions; procedural
      success with no in-hospital complications was observed in types IVb and Ia
      lesions.

PMID- 19379474
TI  - Update on dedicated bifurcation stents.
AB  - Coronary bifurcation lesions represent an area of ongoing challenge in
      interventional cardiology. Contemporary studies using drug-eluting stents report
      a reduction in main vessel (MV) restenosis; however, residual stenosis and
      restenosis at side-branch ostium remain an issue. Multiple two-stent bifurcation
      strategies exist, including T-stenting, V-stenting, simultaneous kissing
      stenting, culotte stenting, and crush stenting technique. Each strategy has its
      own advantages and disadvantages, but on the basis of results of numerous
      randomized trials, the provisional approach of implanting one stent on the main
      branch has became the default approach to most bifurcation lesions. Dedicated
      bifurcation stents have been designed to specifically address some of the
      shortcomings of the conventional percutaneous approach to bifurcation
      intervention. The majority of the devices are aimed at facilitating the
      provisional approach. Dedicated bifurcation stents should enable all operators to
      treat the side-branch ostium simultaneously with the main branch, preserving a
      safe, permanent access to side branch during the procedure. In the future, the
      use of these new devices will probably enhance the interaction between adequate
      mechanical scaffolding and accurate delivery of the appropriate dosage of any new
      antirestenosis drugs. There are currently 11 devices available that either have
      completed or are undergoing first-in-man trials. The development of further drug
      eluting platforms and larger controlled studies should demonstrate their clinical
      applicability, efficacy, and safety before they are widely incorporated into
      daily practice.

PMID- 19379475
TI  - A new pan-nitinol occluder for transcatheter closure of ventricular septal
      defects in a canine model.
AB  - BACKGROUND: The Amplatzer ventricular septal defect (VSD) occluder has a fixed
      stainless steel pin bottom protruding out of the surface at the center of the
      discs on both sides. Theoretically, this protruding bottom may interfere with
      epithelialization or, in some cases, cause thrombosis. OBJECTIVE: To evaluate a
      new type of pan-nitinol VSD occluder without the protruding stainless steel pin
      bottom on both sides in a canine VSD model designed to ensure safety,
      effectiveness, and feasibility. METHODS AND RESULTS: VSDs were successfully
      created by transseptal ventricular septal puncture with a Brockenbrough needle
      and dilation with an 8-mm-diameter balloon via the right jugular vein in 9 out of
      12 canines. The new type VSD occluder was successfully implanted in 8 of the 9
      modeled canines. No procedure- or device-related complication was observed.
      Transthoracic echocardiography and MRI 2 months after device implantations showed
      that there was no device dislocation or heart valve dysfunction in 6 of the 8
      tested canines. In addition, gross and pathological examinations 3-6 months after
      implantation showed no corrosion of the devices or serious inflammatory reactions
      in the modeled animals. Complete endothelialization was seen over the surface of
      the discs. CONCLUSIONS: The new pan-nitinol VSD device can be successfully
      implanted in a canine VSD model via a transcatheter approach featuring high
      success rate, low risk of procedure-related complications, and sound
      biocompatibility. The result suggests that this new VSD occluder could be used
      safely in future clinical trials for further test.

PMID- 19379477
TI  - Pain in the lumbar, thoracic or cervical regions: do age and gender matter? A
      population-based study of 34,902 Danish twins 20-71 years of age.
AB  - BACKGROUND: It is unclear to what extent spinal pain varies between genders and
      in relation to age. It was the purpose of this study to describe the self
      reported prevalence of 1) pain ever and pain in the past year in each of the
      three spinal regions, 2) the duration of such pain over the past year, 3) pain
      radiating from these areas, and 4) pain in one, two or three areas. In addition,
      5) to investigate if spinal pain reporting is affected by gender and 6) to see if
      it increases gradually with increasing age. METHOD: A cross-sectional survey was
      conducted in 2002 on 34,902 twin individuals, aged 20 to 71 years, representative
      of the general Danish population. Identical questions on pain were asked for the
      lumbar, thoracic and cervical regions. RESULTS: Low back pain was most common,
      followed by neck pain with thoracic pain being least common. Pain for at least 30
      days in the past year was reported by 12%, 10%, and 4%, respectively. The one-yr
      prevalence estimates of radiating pain were 22% (leg), 16% (arm), and 5% (chest).
      Pain in one area only last year was reported by 20%, followed by two (13%) and
      three areas (8%).Women were always more likely to report pain and they were also
      more likely to have had pain for longer periods. Lumbar and cervical pain peaked
      somewhat around the middle years but the curves were flatter for thoracic pain.
      Similar patterns were noted for radiating pain. Older people did not have pain in
      a larger number of areas but their pain lasted longer. CONCLUSION: Pain reported
      for and from the lumbar and cervical spines was found to be relatively common
      whereas pain in the thoracic spine and pain radiating into the chest was much
      less common. Women were, generally, more likely to report pain than men. The
      prevalence estimates changed surprisingly little over age and were certainly not
      more common in the oldest groups, although the pain was reported as more long
      lasting in the older group.

PMID- 19379478
TI  - Occupational voice demands and their impact on the call-centre industry.
AB  - BACKGROUND: Within the last decade there has been a growth in the call-centre
      industry in the UK, with a growing awareness of the voice as an important tool
      for successful communication. Occupational voice problems such as occupational
      dysphonia, in a business which relies on healthy, effective voice as the primary
      professional communication tool, may threaten working ability and occupational
      health and safety of workers. While previous studies of telephone call-agents
      have reported a range of voice symptoms and functional vocal health problems,
      there have been no studies investigating the use and impact of vocal performance
      in the communication industry within the UK. This study aims to address a
      significant gap in the evidence-base of occupational health and safety research.
      The objectives of the study are: 1. to investigate the work context and vocal
      communication demands for call-agents; 2. to evaluate call-agents' vocal health,
      awareness and performance; and 3. to identify key risks and training needs for
      employees and employers within call-centres. METHODS AND DESIGN: This is an
      occupational epidemiological study, which plans to recruit call-centres
      throughout the UK and Ireland. Data collection will consist of three components:
      1. interviews with managers from each participating call-centre to assess their
      communication and training needs; 2. an online biopsychosocial questionnaire will
      be administered to investigate the work environment and vocal demands of call
      agents; and 3. voice acoustic measurements of a random sample of participants
      using the Multi-dimensional Voice Program (MDVP). Qualitative content analysis
      from the interviews will identify underlying themes and issues. A multivariate
      analysis approach will be adopted using Structural Equation Modelling (SEM), to
      develop voice measurement models in determining the construct validity of
      potential factors contributing to occupational dysphonia. Quantitative data will
      be analysed using SPSS version 15. Ethical approval is granted for this study
      from the School of Communication, University of Ulster. DISCUSSION: The results
      from this study will provide the missing element of voice-based evidence, by
      appraising the interactional dimensions of vocal health and communicative
      performance. This information will be used to inform training for call-agents and
      to contribute to health policies within the workplace, in order to enhance vocal
      health.

PMID- 19379479
TI  - Semi-automated quantification of left ventricular volumes and ejection fraction
      by real-time three-dimensional echocardiography.
AB  - BACKGROUND: Recent studies have shown that real-time three-dimensional (3D)
      echocardiography (RT3DE) gives more accurate and reproducible left ventricular
      (LV) volume and ejection fraction (EF) measurements than traditional two
      dimensional methods. A new semi-automated tool (4DLVQ) for volume measurements in
      RT3DE has been developed. We sought to evaluate the accuracy and repeatability of
      this method compared to a 3D echo standard. METHODS: LV end-diastolic volumes
      (EDV), end-systolic volumes (ESV), and EF measured using 4DLVQ were compared with
      a commercially available semi-automated analysis tool (TomTec 4D LV-Analysis ver.
      2.2) in 35 patients. Repeated measurements were performed to investigate inter-
      and intra-observer variability. RESULTS: Average analysis time of the new tool
      was 141s, significantly shorter than 261s using TomTec (p < 0.001). Bland Altman
      analysis revealed high agreement of measured EDV, ESV, and EF compared to TomTec
      (p = NS), with bias and 95% limits of agreement of 2.1 +/- 21 ml, -0.88 +/- 17
      ml, and 1.6 +/- 11% for EDV, ESV, and EF respectively. Intra-observer variability
      of 4DLVQ vs. TomTec was 7.5 +/- 6.2 ml vs. 7.7 +/- 7.3 ml for EDV, 5.5 +/- 5.6 ml
      vs. 5.0 +/- 5.9 ml for ESV, and 3.0 +/- 2.7% vs. 2.1 +/- 2.0% for EF (p = NS).
      The inter-observer variability of 4DLVQ vs. TomTec was 9.0 +/- 5.9 ml vs. 17 +/-
      6.3 ml for EDV (p < 0.05), 5.0 +/- 3.6 ml vs. 12 +/- 7.7 ml for ESV (p < 0.05),
      and 2.7 +/- 2.8% vs. 3.0 +/- 2.1% for EF (p = NS). CONCLUSION: In conclusion, the
      new analysis tool gives rapid and reproducible measurements of LV volumes and EF,
      with good agreement compared to another RT3DE volume quantification tool.

PMID- 19379480
TI  - Comparison of 2D and 3D calculation of left ventricular torsion as
      circumferential-longitudinal shear angle using cardiovascular magnetic resonance
      tagging.
AB  - PURPOSE: To compare left ventricular (LV) torsion represented as the
      circumferential-longitudinal (CL) shear angle between 2D and 3D quantification,
      using cardiovascular magnetic resonance (CMR). METHODS: CMR tagging was performed
      in six healthy volunteers. From this, LV torsion was calculated using a 2D and a
      3D method. The cross-correlation between both methods was evaluated and
      comparisons were made using Bland-Altman analysis. RESULTS: The cross-correlation
      between the curves was r2 = 0.97 +/- 0.02. No significant time-delay was observed
      between the curves. Bland-Altman analysis revealed a significant positive linear
      relationship between the difference and the average value of both analysis
      methods, with the 2D results showing larger values than the 3D. The difference
      between both methods can be explained by the definition of the 2D method.
      CONCLUSION: LV torsion represented as CL shear quantified by the 2D and 3D
      analysis methods are strongly related. Therefore, it is suggested to use the
      faster 2D method for torsion calculation.

PMID- 19379482
TI  - Functional annotation of the human retinal pigment epithelium transcriptome.
AB  - BACKGROUND: To determine level, variability and functional annotation of gene
      expression of the human retinal pigment epithelium (RPE), the key tissue involved
      in retinal diseases like age-related macular degeneration and retinitis
      pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63
      78 years) were laser dissected and used for 22k microarray studies (Agilent
      technologies). Data were analyzed with Rosetta Resolver, the web tool DAVID and
      Ingenuity software. RESULTS: In total, we identified 19,746 array entries with
      significant expression in the RPE. Gene expression was analyzed according to
      expression levels, interindividual variability and functionality. A group of
      highly (n = 2,194) expressed RPE genes showed an overrepresentation of genes of
      the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group
      of moderately expressed genes (n = 8,776) genes of the phosphatidylinositol
      signaling system and aminosugars metabolism were overrepresented. As expected,
      the top 10 percent (n = 2,194) of genes with the highest interindividual
      differences in expression showed functional overrepresentation of the complement
      cascade, essential in inflammation in age-related macular degeneration, and other
      signaling pathways. Surprisingly, this same category also includes the genes
      involved in Bruch's membrane (BM) composition. Among the top 10 percent of genes
      with low interindividual differences, there was an overrepresentation of genes
      involved in local glycosaminoglycan turnover. CONCLUSION: Our study expands
      current knowledge of the RPE transcriptome by assigning new genes, and adding
      data about expression level and interindividual variation. Functional annotation
      suggests that the RPE has high levels of protein synthesis, strong energy
      demands, and is exposed to high levels of oxidative stress and a variable degree
      of inflammation. Our data sheds new light on the molecular composition of BM,
      adjacent to the RPE, and is useful for candidate retinal disease gene
      identification or gene dose-dependent therapeutic studies.

PMID- 19379481
TI  - A transcriptional sketch of a primary human breast cancer by 454 deep sequencing.
AB  - BACKGROUND: The cancer transcriptome is difficult to explore due to the
      heterogeneity of quantitative and qualitative changes in gene expression linked
      to the disease status. An increasing number of "unconventional" transcripts, such
      as novel isoforms, non-coding RNAs, somatic gene fusions and deletions have been
      associated with the tumoral state. Massively parallel sequencing techniques
      provide a framework for exploring the transcriptional complexity inherent to
      cancer with a limited laboratory and financial effort. We developed a deep
      sequencing and bioinformatics analysis protocol to investigate the molecular
      composition of a breast cancer poly(A)+ transcriptome. This method utilizes a
      cDNA library normalization step to diminish the representation of highly
      expressed transcripts and biology-oriented bioinformatic analyses to facilitate
      detection of rare and novel transcripts. RESULTS: We analyzed over 132,000 Roche
      454 high-confidence deep sequencing reads from a primary human lobular breast
      cancer tissue specimen, and detected a range of unusual transcriptional events
      that were subsequently validated by RT-PCR in additional eight primary human
      breast cancer samples. We identified and validated one deletion, two novel ncRNAs
      (one intergenic and one intragenic), ten previously unknown or rare transcript
      isoforms and a novel gene fusion specific to a single primary tissue sample. We
      also explored the non-protein-coding portion of the breast cancer transcriptome,
      identifying thousands of novel non-coding transcripts and more than three hundred
      reads corresponding to the non-coding RNA MALAT1, which is highly expressed in
      many human carcinomas. CONCLUSION: Our results demonstrate that combining 454
      deep sequencing with a normalization step and careful bioinformatic analysis
      facilitates the discovery and quantification of rare transcripts or ncRNAs, and
      can be used as a qualitative tool to characterize transcriptome complexity,
      revealing many hitherto unknown transcripts, splice isoforms, gene fusion events
      and ncRNAs, even at a relatively low sequence sampling.

PMID- 19379483
TI  - Prophylaxis of heterotopic ossification - an updated review.
AB  - Heterotopic ossification (HO) is defined as the process by which trabecular bone
      forms outside of the skeletal structure, occupying space in soft tissue where it
      does not normally exist. The current popular prophylactic treatment modalities
      include non-steroidal anti-inflammatory drugs (NSAIDs) and radiation therapy,
      although the literature remains inconclusive as to which is superior.
      Additionally, both treatments can lead to adverse effects to the patient.
      Recently there have been several studies attempting to identify new aspects of
      the etiology of heterotopic bone formation and introduce new prophylactic
      modalities with increased efficacy and fewer side effects. For this review, we
      selectively retrieved articles from Medline published from 1958-2008 on the
      prophylaxis of HO with the aim of assisting readers in quickly grasping the
      current status of research and clinical aspects of HO prophylaxis.

PMID- 19379484
TI  - The p53HMM algorithm: using profile hidden markov models to detect p53-responsive
      genes.
AB  - BACKGROUND: A computational method (called p53HMM) is presented that utilizes
      Profile Hidden Markov Models (PHMMs) to estimate the relative binding affinities
      of putative p53 response elements (REs), both p53 single-sites and cluster-sites.
      These models incorporate a novel "Corresponded Baum-Welch" training algorithm
      that provides increased predictive power by exploiting the redundancy of
      information found in the repeated, palindromic p53-binding motif. The predictive
      accuracy of these new models are compared against other predictive models,
      including position specific score matrices (PSSMs, or weight matrices). We also
      present a new dynamic acceptance threshold, dependent upon a putative binding
      site's distance from the Transcription Start Site (TSS) and its estimated binding
      affinity. This new criteria for classifying putative p53-binding sites increases
      predictive accuracy by reducing the false positive rate. RESULTS: Training a
      Profile Hidden Markov Model with corresponding positions matching a combined
      palindromic p53-binding motif creates the best p53-RE predictive model. The
      p53HMM algorithm is available on-line: (http://tools.csb.ias.edu). CONCLUSION:
      Using Profile Hidden Markov Models with training methods that exploit the
      redundant information of the homotetramer p53 binding site provides better
      predictive models than weight matrices (PSSMs). These methods may also boost
      performance when applied to other transcription factor binding sites.

PMID- 19379486
TI  - Edible aquatic Coleoptera of the world with an emphasis on Mexico.
AB  - Anthropoentomophagy is an ancient culinary practice wherein terrestrial and
      aquatic insects are eaten by humans. Of these species of insects, terrestrial
      insects are far more commonly used in anthropoentomophagy than aquatic insects.
      In this study we found that there are 22 genera and 78 species of edible aquatic
      beetles in the world. The family Dytiscidae hosts nine genera, Gyrinidae one,
      Elmidae two, Histeridae one, Hydrophilidae six, Haliplidae two and Noteridae one.
      Of the recorded species, 45 correspond to the family Dytiscidae, 19 to
      Hydrophilidae, three to Gyrinidae, four to Elmidae, two to Histeridae, four to
      Haliplidae and one to Noteridae. These beetles are the most prized organisms of
      lentic waters. The family that has the highest number of edible food insect
      genera and species is Dytiscidae. Here, the global geographic distribution of
      species in these organisms is shown, and a discussion is presented of its
      importance as a renewable natural resource widely used for food in various
      countries.

PMID- 19379485
TI  - Mouse H6 Homeobox 1 (Hmx1) mutations cause cranial abnormalities and reduced body
      mass.
AB  - BACKGROUND: The H6 homeobox genes Hmx1, Hmx2, and Hmx3 (also known as Nkx5-3;
      Nkx5-2 and Nkx5-1, respectively), compose a family within the NKL subclass of the
      ANTP class of homeobox genes. Hmx gene family expression is mostly limited to
      sensory organs, branchial (pharyngeal) arches, and the rostral part of the
      central nervous system. Targeted mutation of either Hmx2 or Hmx3 in mice disrupts
      the vestibular system. These tandemly duplicated genes have functional overlap as
      indicated by the loss of the entire vestibular system in double mutants. Mutants
      have not been described for Hmx1, the most divergent of the family. RESULTS:
      Dumbo (dmbo) is a semi-lethal mouse mutation that was recovered in a forward
      genetic mutagenesis screen. Mutants exhibit enlarged ear pinnae with a
      distinctive ventrolateral shift. Here, we report on the basis of this phenotype
      and other abnormalities in the mutant, and identify the causative mutation as
      being an allele of Hmx1. Examination of dumbo skulls revealed only subtle changes
      in cranial bone morphology, namely hyperplasia of the gonial bone and
      irregularities along the caudal border of the squamous temporal bone. Other
      nearby otic structures were unaffected. The semilethality of dmbo/dmbo mice was
      found to be ~40%, occured perinatally, and was associated with exencephaly.
      Surviving mutants of both sexes exhibited reduced body mass from ~3 days
      postpartum onwards. Most dumbo adults were microphthalmic. Recombinant animals
      and specific deletion-bearing mice were used to map the dumbo mutation to a 1.8
      Mb region on Chromosome 5. DNA sequencing of genes in this region revealed a
      nonsense mutation in the first exon of H6 Homeobox 1 (Hmx1; also Nkx5-3). An
      independent spontaneous allele called misplaced ears (mpe) was also identified,
      confirming Hmx1 as the responsible mutant gene. CONCLUSION: The divergence of
      Hmx1 from its paralogs is reflected by different and diverse developmental roles
      exclusive of vestibular involvement. Additionally, these mutant Hmx1 alleles
      represent the first mouse models of a recently-discovered Oculo-Auricular
      syndrome caused by mutation of the orthologous human gene.

PMID- 19379487
TI  - Behavioural and electrophysiological characterisation of experimentally induced
      osteoarthritis and neuropathy in C57Bl/6 mice.
AB  - BACKGROUND: Osteoarthritis is a widespread condition affecting the elderly where
      approximately 70-90% of over 75 year olds are affected, representing one of the
      largest cost burdens to healthcare in the western world. The monosodium
      iodoacetate (MIA) osteoarthritis model has been well described in the rat
      especially in terms of the pathological progression of the disease and more
      recently pain behaviour. In this study, we characterise, for the first time, MIA
      induced osteoarthritis in mice and compare it with nerve-injured mice (partial
      sciatic nerve injury), using both behavioural and in vivo electrophysiological
      measurements. These approaches uniquely allow the threshold and suprathreshold
      measures to many modalities to be quantified and so form a basis for improving
      and expanding transgenic studies. RESULTS: Significant mechanical
      hypersensitivity was observed in the ipsilateral hindpaw in MIA injected mice at
      all observed time points following infrapetellar MIA injection (p < 0.05). The
      mechanical hypersensitivity exhibited a partial biphasic temporal pattern, but
      thermal hypersensitivity was absent. Electrically-evoked dorsal horn neuronal
      responses in MIA injected mice were significantly elevated (p < 0.05) with
      respect to A- and C-fibre firing, input, pinch and noxious von Frey (26 and 60
      g). No significant changes in A- or C-fibre thresholds were observed. Nerve
      injured mice displayed significant behavioural thermal and mechanical
      hypersensitivity (p < 0.05) and evoked dorsal horn responses were significantly
      increased with respect to C-fibre firing, pinch and wind-up (p < 0.05).
      CONCLUSION: The MIA model of osteoarthritic pain in mice displays behavioural
      characteristics similar to those observed in rats. Changes in both behavioural
      measures and neuronal activity from the paw, suggest that central changes are
      involved in this pain state, although a role for peripheral drives is also
      likely. Moreover, the behavioural and neuronal measures in these two pain models
      showed overlapping alterations in terms of certain neuronal measures and
      mechanical sensitivity despite their very different pathologies and a loss of
      input in neuropathy, suggesting some commonalities in the central processing of
      different peripheral pain states. This murine model of osteoarthritis will allow
      the exploitation of knock out animals to better understand underlying mechanisms
      and identify novel molecular targets.

PMID- 19379488
TI  - Enhanced release of IgE-dependent early phase mediators from nasal polyp tissue.
AB  - BACKGROUND: The mast cell is a crucial effector cell in allergic rhinitis and
      other inflammatory diseases. During the acute allergic reaction preformed
      mediators such as histamine, but also de novo produced mediators such as
      leukotrienes (LTC4/D4/E4) and prostaglandins (PGD2) are released. Mast cells
      represent targets for therapeutic intervention, and thus a human ex-vivo model to
      stimulate mast cells taken from mucosal sites would be instrumental for drug
      intervention studies. We have aimed to activate mast cells within ex-vivo human
      nasal tissue by IgE/anti-IgE specific (epsilon chain specific) stimulations and
      in this respect to test the usability of nasal polyps versus inferior turbinates
      METHODS: Biopsy samples were collected from patients with nasal polyps and
      inferior turbinates from patients who underwent sinus or septal surgery. Tissue
      fragments were primed with IgE 1 mug/ml for 60 minutes and then stimulated for 30
      minutes with tissue culture medium (negative control), anti-IgE 10 mug/ml, anti
      IgE 30 mug/ml and ionomycin 10 muM (positive control). Histamine, leukotrienes
      and PGD2 were measured in supernatants. To help provide an understanding of the
      extent of the response, the number of tryptase and FcepsilonRIalpha positive
      cells was evaluated by means of immunohistochemistry and the FcepsilonRIalpha
      chain was measured by means of quantitative PCR in the nasal polyp and inferior
      turbinate tissues. Finally, the correlation between IgE concentrations in the
      nasal tissue and the release of mediators was analysed. RESULTS: Stimulations
      with anti-IgE on IgE-primed nasal tissue fragments lead to a concentration
      dependent release of histamine, leukotrienes and PGD2. The release of these early
      phase mediators was significantly higher in nasal polyps compared to inferior
      turbinates, although tryptase, FcepsilonRIalpha positive cells and
      FcepsilonRIalpha-chain transcripts were equally present in both groups. No
      correlation was found between baseline concentrations of IgE, and the release of
      histamine, LTC4/LTD4/LTE4 and PGD2 after stimulation. CONCLUSION: This human
      nasal challenge model mimics the allergic early phase reaction. The release of
      histamine, cys-leukotrienes and PGD2 was significantly higher in nasal polyps
      versus inferior turbinates, however, this observation could not be explained by
      differences in mast cell or FcepsilonRI+ cell numbers.

PMID- 19379489
TI  - Small noncoding RNA GcvB is a novel regulator of acid resistance in Escherichia
      coli.
AB  - BACKGROUND: The low pH environment of the human stomach is lethal for most
      microorganisms; but not Escherichia coli, which can tolerate extreme acid stress.
      Acid resistance in E. coli is hierarchically controlled by numerous regulators
      among which are small noncoding RNAs (sncRNA). RESULTS: In this study, we
      individually deleted seventy-nine sncRNA genes from the E. coli K12-MG1655
      chromosome, and established a single-sncRNA gene knockout library. By
      systematically screening the sncRNA mutant library, we show that the sncRNA GcvB
      is a novel regulator of acid resistance in E. coli. We demonstrate that GcvB
      enhances the ability of E. coli to survive low pH by upregulating the levels of
      the alternate sigma factor RpoS. CONCLUSION: GcvB positively regulates acid
      resistance by affecting RpoS expression. These data advance our understanding of
      the sncRNA regulatory network involved in modulating acid resistance in E. coli.

PMID- 19379490
TI  - Invasive Haemophilus influenzae infections in Germany: impact of non-type b
      serotypes in the post-vaccine era.
AB  - BACKGROUND: Haemophilus influenzae type b (Hib) vaccination led to a significant
      decrease in invasive bacterial infections in children. The aim of this study was
      to assess a potential shift to more non-type b invasive infections in a
      population with high Hib vaccination coverage and to compare the burden of
      suffering between children with Hib, capsulated non-b and non-capsulated Hi
      infections. METHODS: Cases with confirmed invasive Hi infections were ascertained
      through two independent nationwide active surveillance systems in 1998-2005.
      Information on possible predisposing conditions and clinical information was
      available from 2001 onwards. RESULTS: The total number of reported non-type b Hi
      cases varied between 10 cases in 1998, 27 in 2000 and 14 in 2005. In each year,
      non-capsulated serotypes outnumbered capsulated non-type b ones. 192 cases were
      detected in 2001-2005, more than one half was non-type b and 88% of the non-type
      b cases were non-capsulated. For cases with Hib/capsulated non-type b infections
      the most common clinical presentation was meningitis (67% each); 89%/78% had no
      potential predisposing condition, 75%/72% completely recovered from disease and
      6% (each) died. In contrast, meningitis was diagnosed in 34% of the non
      capsulated Hi infections, septicaemia in 28% and pneumonia 21%; 62% had no
      potential predisposing condition, 83% completely recovered and 3% died.
      CONCLUSION: There was no increase in non-type b Hi invasive infections during 8
      years of active surveillance in Germany. Invasive disease due to non-type b Hi is
      not confined to children with risk factors. In patients with capsulated non-type
      b Hi infections the proportion of meningitis cases is similar to Hib, but double
      as high as in non-capsulated Hi.

PMID- 19379491
TI  - Head to head comparisons of two modalities of perfusion adenosine stress
      echocardiography with simultaneous SPECT.
AB  - BACKGROUND: Real-time perfusion (RTP) contrast echocardiography can be used
      during adenosine stress echocardiography (ASE) to evaluate myocardial ischemia.
      We compared two different types of RTP power modulation techniques, angiomode
      (AM) and high-resolution grayscale (HR), with 99mTc-tetrofosmin single-photon
      emission computed tomography (SPECT) for the detection of myocardial ischemia.
      METHODS: Patients with known or suspected coronary artery disease (CAD), admitted
      to SPECT, were prospectively invited to participate. Patients underwent RTP
      imaging (SONOS 5500) using AM and HR during Sonovue(R) infusion, before and
      throughout the adenosine stress, also used for SPECT. Analysis of myocardial
      perfusion and wall motion by RTP-ASE were done for AM and HR at different time
      points, blinded to one another and to SPECT. Each segment was attributed to one
      of the three main coronary vessel areas of interest. RESULTS: In 50 patients, 150
      coronary areas were analyzed by SPECT and RTP-ASE AM and HR. SPECT showed
      evidence of ischemia in 13 out of 50 patients. There was no significant
      difference between AM and HR in detecting ischemia (p = 0.08). The agreement for
      AM and HR, compared to SPECT, was 93% and 96%, with Kappa values of 0.67 and
      0.75, respectively (p < 0.001). CONCLUSION: There was no significant difference
      between AM and HR in correctly detecting myocardial ischemia as judged by SPECT.
      This suggests that different types of RTP modalities give comparable data during
      RTP-ASE in patients with known or suspected CAD.

PMID- 19379492
TI  - Constitutive basal and stimulated human small bowel contractility is enhanced in
      obesity.
AB  - Small bowel contractility may be more prominent in obese subjects, such that
      there is enhanced nutrient absorption and hunger stimulation. However, there is
      little evidence to support this. This study examined in vitro small bowel
      contractility in obese patients versus non-obese patients. Samples of
      histologically normal small bowel were obtained at laparoscopic Roux-en-Y gastric
      bypass from obese patients. Control specimens were taken from non-obese patients
      undergoing small bowel resection for benign disease or formation of an ileal
      pouch-anal anastomosis. Samples were transported in a pre-oxygenated Krebs
      solution. Microdissected circular smooth muscle strips were suspended under 1 g
      of tension in organ baths containing Krebs solution oxygenated with 95% O2/5% CO2
      at 37 degrees C. Contractile activity was recorded using isometric transducers at
      baseline and in response to receptor-mediated contractility using prostaglandin
      F2a, a nitric oxide donor and substance P under both equivocal and non
      adrenergic, non-cholinergic conditions (guanethidine and atropine). Following
      equilibration, the initial response to the cholinergic agonist carbachol (0.1
      mmol/L) was significantly increased in the obese group (n = 63) versus the lean
      group (n = 61) with a mean maximum response: weight ratio of 4.58 +/- 0.89 vs
      3.53 +/- 0.74; (p = 0.032). Following washout and re-calibration, cumulative
      application of substance P and prostaglandin F2a produced concentration-dependent
      contractions of human small bowel smooth muscle strips. Contractile responses of
      obese small bowel under equivocal conditions were significantly increased
      compared with non-obese small bowel (p < 0.05 for all agonists). However, no
      significant differences were shown between the groups when the experiments were
      performed under NANC conditions. There were no significant differences found
      between the groups when challenged with nitric oxide, under either equivocal or
      NANC conditions. Stimulated human small bowel contractility is increased in obese
      patients suggesting faster enteric emptying and more rapid intestinal transit.
      This may translate into enhanced appetite and reduced satiety.

PMID- 19379493
TI  - MHCBN 4.0: A database of MHC/TAP binding peptides and T-cell epitopes.
AB  - BACKGROUND: Many databases housing the information about MHC binders and non
      binders have been developed in the past to help the scientific community working
      in the field of immunology, immune-informatics or vaccine design. As the
      information about these MHC binding and non-binding peptides continues to grow
      with the time and there is a need to keep the databases updated. So, in order to
      provide the immunological fraternity with the most recent information we need to
      maintain and update our database regularly. In this paper, we describe the
      updated version of 4.0 of the database MHCBN. FINDINGS: MHCBN is a comprehensive
      database comprising over 25,857 peptide sequences (1053 TAP binding peptides),
      whose binding affinity with either MHC or TAP molecules has been assayed
      experimentally. It is a manually curated database where entries are collected &
      compiled from published literature and existing immunological public databases.
      MHCBN has a number of web-based tools for the analysis and retrieval of
      information like mapping of antigenic regions, creation of allele specific
      dataset, BLAST search, various diseases associated with MHC alleles etc. Further,
      all entries are hyper linked to major databases like SWISS-PROT, PDB etc. to
      provide the information beyond the scope of MHCBN. The latest version 4.0 of
      MHCBN has 6080 more entries than previously published version 1.1. CONCLUSION:
      MHCBN database updating is meant to facilitate immunologist in understanding the
      immune system and provide them the latest information. We feel that our database
      will complement the existing databases in serving scientific community.

PMID- 19379494
TI  - Competency, confidence and conflicting evidence: key issues affecting health
      visitors' use of research evidence in practice.
AB  - BACKGROUND: Health visitors play a pivotal position in providing parents with up
      to-date evidence-based care on child health. The recent controversy over the
      safety of the MMR vaccine has drawn attention to the difficulties they face when
      new research which raises doubts about current guidelines and practices is
      published. In the aftermath of the MMR controversy, this paper investigates the
      sources health visitors use to find out about new research evidence on
      immunisation and examines barriers and facilitators to using evidence in
      practice. It also assesses health visitors' confidence in using research
      evidence. METHODS: Health visitors were recruited from the 2007 UK Community
      Practitioners' and Health Visitors' Association conference. All delegates were
      eligible to complete the questionnaire if in their current professional role they
      advise parents about childhood immunisation or administer vaccines to children.
      Of 228 who were eligible, 185 completed the survey (81.1%). RESULTS: These health
      visitors used a wide range of resources to find out about new research evidence
      on childhood immunisation. Popular sources included information leaflets and
      publications, training days, nursing journals and networking with colleagues. A
      lack of time was cited as the main barrier to searching for new evidence. The
      most common reason given for not using research in practice was a perception of
      conflicting research evidence. Understanding the evidence was a key facilitator.
      Health visitors expressed less confidence about searching and explaining research
      on childhood immunisation than evidence on weaning and a baby's sleep position.
      CONCLUSION: Even motivated health visitors feel they lack the time and, in some
      cases, the skills to locate and appraise research evidence. This research
      suggests that of the provision of already-appraised research would help to keep
      busy health professionals informed, up-to-date and confident in responding to
      public concerns, particularly when there is apparently conflicting evidence.
      Health visitors' relative lack of confidence about research on immunisation
      suggests there is still a job to be done in rebuilding confidence in evidence on
      childhood immunisation. Further research on what makes evidence more
      comprehensible, convincing and useable would contribute to understanding how to
      bridge the gulf between evidence and practice.

PMID- 19379495
TI  - Molecular ageing in progeroid syndromes: Hutchinson-Gilford progeria syndrome as
      a model.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder
      that belongs to a group of conditions called laminopathies which affect nuclear
      lamins. Mutations in two genes, LMNA and ZMPSTE24, have been found in patients
      with HGPS. The p.G608G LMNA mutation is the most commonly reported mutation. The
      aim of this work was to compile a comprehensive literature review of the clinical
      features and genetic mutations and mechanisms of this syndrome as a contribution
      to health care workers. This review shows the necessity of a more detailed
      clinical identification of Hutchinson-Gilford progeria syndrome and the need for
      more studies on the pharmacologic and pharmacogenomic approach to this syndrome.

PMID- 19379496
TI  - Malaria transmission in non-endemic areas: case report, review of the literature
      and implications for public health management.
AB  - In non-endemic areas, malaria is rare and locally acquired infections,
      particularly with Plasmodium falciparum, are exceptional events. The diagnosis
      is, therefore, likely to be delayed or missed in patients without a relevant
      travel history. This report describes a case of falciparum malaria in Berlin,
      Germany, in a patient who had not been to an endemic area for more than a decade.
      Potential routes of vector-related and direct transmission were evaluated,
      particularly with regard to a possible danger to the public. A review of the
      literature was conducted regarding possible routes of transmission and their
      probability assessed. Genotyping of parasite isolates of this and another patient
      with malaria admitted 16 days before revealed homology between the two strains.
      In a local entomological survey, anopheline vectors on the hospital grounds as
      well as in the residential area of both patients were found. Despite intensive
      investigations, the mode of transmission remained obscure. In this context,
      possible routes of vector-borne and direct occupational/accidental transmission
      in a major European city are reviewed and discussed, providing information and
      guidance in case other similar events occur elsewhere. Examples for
      investigations and measures to be taken in such a situation are provided. When
      local malaria transmission within a large non-immune population cannot be ruled
      out, genotyping of parasite isolates, local entomological surveys, preparedness
      for secondary cases, expert consultations in a multidisciplinary team and careful
      information management are essential. Malaria acquired in non-endemic areas
      remains an unlikely, but possible event for which awareness needs to be
      maintained.

PMID- 19379497
TI  - A comparison of synthetic oligodeoxynucleotides, DNA fragments and AAV-1 for
      targeted episomal and chromosomal gene repair.
AB  - BACKGROUND: Current strategies for gene therapy of inherited diseases consist in
      adding functional copies of the gene that is defective. An attractive alternative
      to these approaches would be to correct the endogenous mutated gene in the
      affected individual. This study presents a quantitative comparison of the repair
      efficiency using different forms of donor nucleic acids, including synthetic DNA
      oligonucleotides, double stranded DNA fragments with sizes ranging from 200 to
      2200 bp and sequences carried by a recombinant adeno-associated virus (rAAV-1).
      Evaluation of each gene repair strategy was carried out using two different
      reporter systems, a mutated eGFP gene or a dual construct with a functional eGFP
      and an inactive luciferase gene, in several different cell systems. Gene
      targeting events were scored either following transient co-transfection of
      reporter plasmids and donor DNAs, or in a system where a reporter construct was
      stably integrated into the chromosome. RESULTS: In both episomal and chromosomal
      assays, DNA fragments were more efficient at gene repair than oligonucleotides or
      rAAV-1. Furthermore, the gene targeting frequency could be significantly
      increased by using DNA repair stimulating drugs such as doxorubicin and
      phleomycin. CONCLUSION: Our results show that it is possible to obtain repair
      frequencies of 1% of the transfected cell population under optimized transfection
      protocols when cells were pretreated with phleomycin using rAAV-1 and dsDNA
      fragments.

PMID- 19379499
TI  - Gender differences in health and health care utilisation in various ethnic groups
      in the Netherlands: a cross-sectional study.
AB  - BACKGROUND: To determine gender differences in health and health care utilisation
      within and between various ethnic groups in the Netherlands. METHODS: Data from
      the second Dutch National Survey of General Practice (2000-2002) were used. A
      total of 7,789 persons from the indigenous population and 1,512 persons from the
      four largest migrant groups in the Netherlands -- Morocco, Netherlands Antilles,
      Turkey and Surinam -- aged 18 years and older were interviewed. Self-reported
      health outcomes studied were general health status and the presence of acute
      (past 14 days) and chronic conditions (past 12 months). And self-reported
      utilisation of the following health care services was analysed: having contacted
      a general practitioner (past 2 months), a medical specialist, physiotherapist or
      ambulatory mental health service (past 12 months), hospitalisation (past 12
      months) and use of medication (past 14 days). Gender differences in these
      outcomes were examined within and between the ethnic groups, using logistic
      regression analyses. RESULTS: In general, women showed poorer health than men;
      the largest differences were found for the Turkish respondents, followed by
      Moroccans, and Surinamese. Furthermore, women from Morocco and the Netherlands
      Antilles more often contacted a general practitioner than men from these
      countries. Women from Turkey were more hospitalised than Turkish men. Women from
      Morocco more often contacted ambulatory mental health care than men from this
      country, and women with an indigenous background more often used over the counter
      medication than men with an indigenous background. CONCLUSION: In general the
      self-reported health of women is worse compared to that of men, although the size
      of the gender differences may vary according to the particular health outcome and
      among the ethnic groups. This information might be helpful to develop policy to
      improve the health status of specific groups according to gender and ethnicity.
      In addition, in some ethnic groups, and for some types of health care services,
      the use by women is higher compared to that by men. More research is needed to
      explain these differences.

PMID- 19379498
TI  - Analysis of the Rickettsia africae genome reveals that virulence acquisition in
      Rickettsia species may be explained by genome reduction.
AB  - BACKGROUND: The Rickettsia genus includes 25 validated species, 17 of which are
      proven human pathogens. Among these, the pathogenicity varies greatly, from the
      highly virulent R. prowazekii, which causes epidemic typhus and kills its
      arthropod host, to the mild pathogen R. africae, the agent of African tick-bite
      fever, which does not affect the fitness of its tick vector. RESULTS: We
      evaluated the clonality of R. africae in 70 patients and 155 ticks, and
      determined its genome sequence, which comprises a circular chromosome of
      1,278,540 bp including a tra operon and an unstable 12,377-bp plasmid. To study
      the genetic characteristics associated with virulence, we compared this species
      to R. prowazekii, R. rickettsii and R. conorii. R. africae and R. prowazekii
      have, respectively, the less and most decayed genomes. Eighteen genes are present
      only in R. africae including one with a putative protease domain upregulated at
      37 degrees C. CONCLUSION: Based on these data, we speculate that a loss of
      regulatory genes causes an increase of virulence of rickettsial species in ticks
      and mammals. We also speculate that in Rickettsia species virulence is mostly
      associated with gene loss.The genome sequence was deposited in GenBank under
      accession number [GenBank: NZ_AAUY01000001].

PMID- 19379500
TI  - Island method for estimating the statistical significance of profile-profile
      alignment scores.
AB  - BACKGROUND: In the last decade, a significant improvement in detecting remote
      similarity between protein sequences has been made by utilizing alignment
      profiles in place of amino-acid strings. Unfortunately, no analytical theory is
      available for estimating the significance of a gapped alignment of two profiles.
      Many experiments suggest that the distribution of local profile-profile alignment
      scores is of the Gumbel form. However, estimating distribution parameters by
      random simulations turns out to be computationally very expensive. RESULTS: We
      demonstrate that the background distribution of profile-profile alignment scores
      heavily depends on profiles' composition and thus the distribution parameters
      must be estimated independently, for each pair of profiles of interest. We also
      show that accurate estimates of statistical parameters can be obtained using the
      "island statistics" for profile-profile alignments. CONCLUSION: The island
      statistics can be generalized to profile-profile alignments to provide an
      efficient method for the alignment score normalization. Since multiple island
      scores can be extracted from a single comparison of two profiles, the island
      method has a clear speed advantage over the direct shuffling method for
      comparable accuracy in parameter estimates.

PMID- 19379501
TI  - Growth inhibition and ultrastructural alterations induced by Delta24(25)-sterol
      methyltransferase inhibitors in Candida spp. isolates, including non-albicans
      organisms.
AB  - BACKGROUND: Although Candida species are commensal microorganisms, they can cause
      many invasive fungal infections. In addition, antifungal resistance can
      contribute to failure of treatment.The purpose of this study was to evaluate the
      antifungal activity of inhibitors of Delta24(25)-sterol methyltransferase (24
      SMTI), 20-piperidin-2-yl-5alpha-pregnan-3beta-20(R)-diol (AZA), and 24(R,S),25
      epiminolanosterol (EIL), against clinical isolates of Candida spp., analysing the
      ultrastructural changes. RESULTS: AZA and EIL were found to be potent growth
      inhibitors of Candida spp. isolates. The median MIC50 was 0.5 microg.ml-1 for AZA
      and 2 microg.ml-1 for EIL, and the MIC90 was 2 microg.ml-1 for both compounds.
      All strains used in this study were susceptible to amphotericin B; however, some
      isolates were fluconazole- and itraconazole-resistant. Most of the azole
      resistant isolates were Candida non-albicans (CNA) species, but several of them,
      such as C. guilliermondii, C. zeylanoides, and C. lipolytica, were susceptible to
      24-SMTI, indicating a lack of cross-resistance. Reference strain C. krusei (ATCC
      6258, FLC-resistant) was consistently susceptible to AZA, although not to EIL.
      The fungicidal activity of 24-SMTI was particularly high against CNA isolates.
      Treatment with sub-inhibitory concentrations of AZA and EIL induced several
      ultrastructural alterations, including changes in the cell-wall shape and
      thickness, a pronounced disconnection between the cell wall and cytoplasm with an
      electron-lucent zone between them, mitochondrial swelling, and the presence of
      electron-dense vacuoles. Fluorescence microscopy analyses indicated an
      accumulation of lipid bodies and alterations in the cell cycle of the yeasts. The
      selectivity of 24-SMTI for fungal cells versus mammalian cells was assessed by
      the sulforhodamine B viability assay. CONCLUSION: Taken together, these results
      suggest that inhibition of 24-SMT may be a novel approach to control Candida spp.
      infections, including those caused by azole-resistant strains.

PMID- 19379502
TI  - The genome and proteome of a virulent Escherichia coli O157:H7 bacteriophage
      closely resembling Salmonella phage Felix O1.
AB  - Based upon whole genome and proteome analysis, Escherichia coli O157:H7-specific
      bacteriophage (phage) wV8 belongs to the new myoviral genus, "the Felix O1-like
      viruses" along with Salmonella phage Felix O1 and Erwinia amylovora phage phiEa21
      4. The genome characteristics of phage wV8 (size 88.49 kb, mol%G+C 38.9, 138
      ORFs, 23 tRNAs) are very similar to those of phage Felix O1 (86.16 kb, 39.0
      mol%G+C, 131 ORFs and 22 tRNAs) and, indeed most of the proteins have their
      closest homologs within Felix O1. Approximately one-half of the Escherichia coli
      O157:H7 mutants resistant to phage wV8 still serotype as O157:H7 indicating that
      this phage may recognize, like coliphage T4, two different surface receptors:
      lipopolysaccharide and, perhaps, an outer membrane protein.

PMID- 19379503
TI  - Single puncture percutaneous nephrolithomy for management of complex renal
      stones.
AB  - BACKGROUND: The purpose of this report is to assess the safety and efficacy of
      single lower pole access for multiple and branched renal calculi. A prospective
      non randomized clinical study included 26 patients with complex renal stones (9
      patients had branched renal stones and the other 17 had multiple renal stones) in
      the period from May 2003 to May 2004. Mean patient age was 42 years +/- 13.2
      (range 18 to 67 years). All patients underwent percutaneous nephrolithotomy
      (PCNL) via a single lower calyceal puncture. Small stones were intactly extracted
      by a range of stone graspers while large stones (smallest diameter more than 1
      cm) were disintegrated using either the pneumatic EMS Swiss lithoclast or Holmium
      YAG laser. Flexible nephroscope was used for stones inaccessible by the rigid
      instruments. FINDINGS: Overall stone-free rate was 74.8%. Patients with residual
      stones were managed by one session of shock wave lithotripsy (SWL). Mean
      operative time was (80 minutes +/- 27.4) for branched stones and (49.1 minutes +/
      15.9) for multiple stones. No significant blood loss reported. Perforation of
      pelvicalyceal system occurred in 2 patients (11.5%) with no serious sequelae.
      Only 1 patient developed secondary hemorrhage which necessitated blood
      transfusion and selective angio-embolization. CONCLUSION: In our hands, the
      efficacy and safety of single lower calyceal puncture PCNL in management of
      complex renal stones are comparable to those of the general procedure stated in
      literature.

PMID- 19379504
TI  - Obituary: hidesaburo hanafusa 1929-2009.

PMID- 19379505
TI  - Metallic nickel nano- and fine particles induce JB6 cell apoptosis through a
      caspase-8/AIF mediated cytochrome c-independent pathway.
AB  - BACKGROUND: Carcinogenicity of nickel compounds has been well documented.
      However, the carcinogenic effect of metallic nickel is still unclear. The present
      study investigates metallic nickel nano- and fine particle-induced apoptosis and
      the signal pathways involved in this process in JB6 cells. The data obtained from
      this study will be of benefit for elucidating the pathological and carcinogenic
      potential of metallic nickel particles. RESULTS: Using 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we found that metallic nickel
      nanoparticles exhibited higher cytotoxicity than fine particles. Both metallic
      nickel nano- and fine particles induced JB6 cell apoptosis. Metallic nickel
      nanoparticles produced higher apoptotic induction than fine particles. Western
      blot analysis showed an activation of proapoptotic factors including Fas (CD95),
      Fas-associated protein with death domain (FADD), caspase-8, death receptor 3
      (DR3) and BID in apoptotic cells induced by metallic nickel particles.
      Immunoprecipitation (IP) western blot analysis demonstrated the formation of the
      Fas-related death-inducing signaling complex (DISC) in the apoptotic process.
      Furthermore, lamin A and beta-actin were cleaved. Moreover, we found that
      apoptosis-inducing factor (AIF) was up-regulated and released from mitochondria
      to cytoplasm. Interestingly, although an up-regulation of cytochrome c was
      detected in the mitochondria of metallic nickel particle-treated cells, no
      cytochrome c release from mitochondria to cytoplasm was found. In addition,
      activation of antiapoptotic factors including phospho-Akt (protein kinase B) and
      Bcl-2 was detected. Further studies demonstrated that metallic nickel particles
      caused no significant changes in the mitochondrial membrane permeability after 24
      h treatment. CONCLUSION: In this study, metallic nickel nanoparticles caused
      higher cytotoxicity and apoptotic induction than fine particles in JB6 cells.
      Apoptotic cell death induced by metallic nickel particles in JB6 cells is through
      a caspase-8/AIF mediated cytochrome c-independent pathway. Lamin A and beta-actin
      are involved in the process of apoptosis. Activation of Akt and Bcl-2 may play an
      important role in preventing cytochrome c release from mitochondria to the
      cytoplasm and may also be important in the carcinogenicity of metallic nickel
      particles. In addition, the results may be useful as an important reference when
      comparing the toxicities of different nickel compounds.

PMID- 19379506
TI  - Breast cancer therapy for BRCA1 carriers: moving towards platinum standard?
AB  - Recently Byrski et al. reported the first-ever breast cancer (BC) study, which
      specifically selected BRCA1-carriers for the neoadjuvant treatment and used
      monotherapy by cisplatin instead of conventional schemes. Although the TNM
      staging of the recruited patients was apparently more favorable than in most of
      published neoadjuvant trials, the results of Byrski et al. clearly outperform any
      historical data. Indeed, 9 of 10 BRCA1-associated BC demonstrated complete
      pathological response to the cisplatin treatment, i.e. these women have good
      chances to be ultimately cured from the cancer disease. High sensitivity of BRCA1
      related tumors to platinating agents has been discussed for years, but it took
      almost a decade to translate convincing laboratory findings into first clinical
      observations. With increasing stratification of tumor disease entities for
      molecular subtypes and rapidly growing armamentarium of cancer drugs, it is
      getting technically and ethically impossible to subject all promising treatment
      options to the large randomized prospective clinical trials. Therefore,
      alternative approaches for initial drugs evaluation are highly required, and one
      of the choices is to extract maximum benefit from already available collections
      of biological material and medical charts. For example, many thousands of BC
      patients around the world have already been subjected to second- or third-line
      therapy with platinum agents, but the association between BRCA status and
      response to the treatment has not been systematically evaluated in these women.
      While potential biases of retrospective studies are widely acknowledged, it is
      frequently ignored that the use of archival collections may provide preliminary
      answers for long-standing questions within days instead of years. However, even
      elegantly-designed, small-sized, hypothesis-generating retrospective studies may
      require multicenter efforts and somewhat cumbersome logistics, that may explain
      the surprising lack of historical data on the platinum-based treatment of BC in
      BRCA1 carriers.

PMID- 19379507
TI  - Natural variation of outcrossing in the hermaphroditic nematode Pristionchus
      pacificus.
AB  - BACKGROUND: Evolution of selfing can be associated with an increase in fixation
      of deleterious mutations, which in certain conditions can lead to species
      extinction. In nematodes, a few species evolved self-fertilization independently,
      making them excellent model systems to study the evolutionary consequences of
      this type of mating system. RESULTS: Here we determine various parameters that
      influence outcrossing in the hermaphroditic nematode Pristionchus pacificus and
      compare them to the better known Caenorhabditis elegans. These nematode species
      are distinct in terms of genetic diversity, which could be explained by
      differences in outcrossing rates. We find that, similarly to C. elegans, P.
      pacificus males are generated at low frequencies from self-fertilizing
      hermaphrodites and are relatively poor mating partners. Furthermore, crosses
      between different isolates reveal that hybrids have lower brood sizes than the
      pure strains, which is a sign of outbreeding depression. In contrast to C.
      elegans, P. pacificus has lower brood sizes and the male X-bearing sperm is able
      to outcompete the X-nullo sperm. CONCLUSION: The results indicate that there is
      no evidence of any selection acting very strongly on P. pacificus males.

PMID- 19379508
TI  - Rodent malaria-resistant strains of the mosquito, Anopheles gambiae, have slower
      population growth than -susceptible strains.
AB  - BACKGROUND: Trade-offs between anti-parasite defence mechanisms and other life
      history traits limit the evolution of host resistance to parasites and have
      important implications for understanding diseases such as malaria. Mosquitoes
      have not evolved complete resistance to malaria parasites and one hypothesis is
      that anti-malaria defence mechanisms are costly. RESULTS: We used matrix
      population models to compare the population growth rates among lines of Anopheles
      gambiae that had been selected for resistance or high susceptibility to the
      rodent malaria parasite, Plasmodium yoelii nigeriensis. The population growth
      rate of the resistant line was significantly lower than that of the highly
      susceptible and the unselected control lines, regardless of whether mosquitoes
      were infected with Plasmodium or not. The lower population growth of malaria
      resistant mosquitoes was caused by reduced post blood-feeding survival of females
      and poor egg hatching. CONCLUSION: With respect to eradicating malaria, the
      strategy of releasing Plasmodium-resistant Anopheles mosquitoes is unlikely to be
      successful if the costs of Plasmodium-resistance in the field are as great as the
      ones measured in this study. High densities of malaria-resistant mosquitoes would
      have to be maintained by continuous release from captive breeding facilities.

PMID- 19379510
TI  - Longitudinal trends in organophosphate incidents reported to the National
      Pesticide Information Center, 1995-2007.
AB  - BACKGROUND: Regulatory decisions to phase-out the availability and use of common
      organophosphate pesticides among the general public were announced in 2000 and
      continued through 2004. Based on revised risk assessments, chlorpyrifos and
      diazinon were determined to pose unacceptable risks. To determine the impact of
      these decisions, organophosphate (OP) exposure incidents reported to the National
      Pesticide Information Center (NPIC) were analyzed for longitudinal trends.
      METHODS: Non-occupational human exposure incidents reported to NPIC were grouped
      into pre- (1995-2000) and post-announcement periods (2001-2007). The number of
      total OP exposure incidents, as well as reports for chlorpyrifos, diazinon and
      malathion, were analyzed for significant differences between these two periods.
      The number of informational inquiries from the general public was analyzed over
      time as well. RESULTS: The number of average annual OP-related exposure incidents
      reported to NPIC decreased significantly between the pre- and post-announcement
      periods (p < 0.001). A significant decrease in the number of chlorpyrifos and
      diazinon reports was observed over time (p < 0.001). No significant difference in
      the number of incident reports for malathion was observed (p = 0.4), which was
      not phased-out of residential use. Similar to exposure incidents, the number of
      informational inquiries received by NPIC declined over time following the phase
      out announcement. CONCLUSION: Consistent with other findings, the number of
      chlorpyrifos and diazinon exposure incidents reported to NPIC significantly
      decreased following public announcement and targeted regulatory action.

PMID- 19379509
TI  - Activation of P2X(7)-mediated apoptosis Inhibits DMBA/TPA-induced formation of
      skin papillomas and cancer in mice.
AB  - BACKGROUND: The study tested the hypothesis that apoptosis can prevent and
      control growth of neoplastic cells. Previous studies in-vitro have shown that the
      pro-apoptotic P2X(7) receptor regulates growth of epithelial cells. The specific
      objective of the present study was to understand to what degree the P2X(7) system
      controls development and growth of skin cancer in vivo, and what cellular and
      molecular mechanisms are involved in the P2X(7) action. METHODS: Skin neoplasias
      in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced
      by local application of DMBA/TPA. Experiments in-vitro utilized cultured
      epidermal keratinocytes generated from wild-type or from P2X(7)-null mice. Assays
      involved protein immunostaining and Western blots; mRNA real-time qPCR; and
      apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as
      solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide
      influx (P2X(7) pore formation) were determined by confocal laser microscopy.
      RESULTS: (a) Co-application on the skin of the P2X7 specific agonist BzATP
      inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the
      completion of study (week 28) the proportion of living animals with cancers in
      the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In
      the normal skin BzATP affected mainly P2X(7)-receptor - expressing proliferating
      keratinocytes, where it augmented apoptosis without evoking inflammatory changes.
      (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in
      normal or papilloma keratinocytes. (d) Levels of P2X(7) receptor, protein and
      mRNA were 4-5 fold lower in cancer tissues than in normal mouse tissues. (e) In
      cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the
      plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced
      apoptosis, pore-formation and augmented calcium influx had similar dose
      dependence for BzATP. (g) Pore formation and the augmented calcium influx were
      depended on the expression of the P2X(7) receptor, while the BzATP-induced
      apoptosis depended on calcium influx. (h) The BzATP-induced apoptosis could be
      blocked by co-treatment with inhibitors of caspase-9 and caspase-3, but not of
      caspase-8. CONCLUSION: (a) P2X(7)-dependent apoptosis is an important mechanism
      that controls the development and progression of epidermal neoplasia in the
      mouse. (b) The P2X(7)-dependent apoptosis is mediated by calcium influx via
      P2X(7) pores, and involves the caspase-9 (mitochondrial) pathway. (c) The
      diminished pro-apoptotic effect of BzATP in mouse cancer keratinocytes is
      possibly the result of low expression of the P2X(7) receptor. (d) Activation of
      P2X(7)-dependent apoptosis, e.g. with BzATP could be a novel chemotherapeutic
      growth-preventive modality for papillomas and epithelial cancers in vivo.

PMID- 19379511
TI  - Serum proteomic profiling and haptoglobin polymorphisms in patients with GVHD
      after allogeneic hematopoietic cell transplantation.
AB  - We studied serum proteomic profiling in patients with graft versus host disease
      (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) by two
      dimensional gel electrophoresis (2-DE) and mass spectrometry analysis. The
      expression of a group of proteins, haptoglobin (Hp), alpha-1-antitrypsin,
      apolipoprotein A-IV, serum paraoxonase and Zn-alpha-glycoprotein were increased
      and the proteins, clusterin precursor, alpha-2-macroglobulin, serum amyloid
      protein precursor, sex hormone-binding globulin, serotransferrin and complement
      C4 were decreased in patients with extensive chronic GVHD (cGVHD). Serum
      haptoglobin (Hp) levels in patients with cGVHD were demonstrated to be
      statistically higher than in patients without cGVHD and normal controls (p <
      0.01). We used immunoblotting and PCR in combination with 2-DE gel image analysis
      to determine Hp polymorphisms in 25 allo-HCT patients and 16 normal donors. The
      results demonstrate that patients with cGVHD had a higher incidence of HP 2-2
      phenotype (43.8%), in comparison to the patients without cGVHD (0%) and normal
      donors (18.7%), suggesting the possibility that specific Hp polymorphism may play
      a role in the development of cGVHD after allo-HCT. In this study, quantitative
      serum Hp levels were shown to be related to cGVHD development. Further, the data
      suggest the possibility that specific Hp polymorphisms may be associated with
      cGVHD development and warrant further investigation.

PMID- 19379512
TI  - Detection of discriminative sequence patterns in the neighborhood of proline cis
      peptide bonds and their functional annotation.
AB  - BACKGROUND: Polypeptides are composed of amino acids covalently bonded via a
      peptide bond. The majority of peptide bonds in proteins is found to occur in the
      trans conformation. In spite of their infrequent occurrence, cis peptide bonds
      play a key role in the protein structure and function, as well as in many
      significant biological processes. RESULTS: We perform a systematic analysis of
      regions in protein sequences that contain a proline cis peptide bond in order to
      discover non-random associations between the primary sequence and the nature of
      proline cis/trans isomerization. For this purpose an efficient pattern discovery
      algorithm is employed which discovers regular expression-type patterns that are
      overrepresented (i.e. appear frequently repeated) in a set of sequences. Four
      types of pattern discovery are performed: i) exact pattern discovery, ii) pattern
      discovery using a chemical equivalency set, iii) pattern discovery using a
      structural equivalency set and iv) pattern discovery using certain amino acids'
      physicochemical properties. The extracted patterns are carefully validated using
      a specially implemented scoring function and a significance measure (i.e. log
      probability estimate) indicative of their specificity. The score threshold for
      the first three types of pattern discovery is 0.90 while for the last type of
      pattern discovery 0.80. Regarding the significance measure, all patterns yielded
      values in the range [-9, -31] which ensure that the derived patterns are highly
      unlikely to have emerged by chance. Among the highest scoring patterns, most of
      them are consistent with previous investigations concerning the neighborhood of
      cis proline peptide bonds, and many new ones are identified. Finally, the
      extracted patterns are systematically compared against the PROSITE database, in
      order to gain insight into the functional implications of cis prolyl bonds.
      CONCLUSION: Cis patterns with matches in the PROSITE database fell mostly into
      two main functional clusters: family signatures and protein signatures. However
      considerable propensity was also observed for targeting signals, active and
      phosphorylation sites as well as domain signatures.

PMID- 19379514
TI  - Outcomes of vaginal hysterectomy for uterovaginal prolapse: a population-based,
      retrospective, cross-sectional study of patient perceptions of results including
      sexual activity, urinary symptoms, and provided care.
AB  - BACKGROUND: Vaginal hysterectomy is often used to correct uterovaginal prolapse,
      however, there is little information regarding outcomes after surgery in routine
      clinical practice. The objective of this study was to investigate complications,
      sexual activity, urinary symptoms, and satisfaction with health care after
      vaginal hysterectomy due to prolapse. METHODS: We analyzed data from the Swedish
      National Register for Gynecological Surgery (SNRGS) from January 1997 to August
      2005. Women participating in the SNRGS were asked to complete surveys at two and
      six months postoperatively. Of 941 women who underwent vaginal hysterectomy for
      uterovaginal prolapse, 791 responded to questionnaires at two months and 682 at
      six months. Complications during surgery and hospital stay were investigated. The
      two-month questionnaire investigated complications after discharge, and patients'
      satisfaction with their health care. Sexual activity and urinary symptoms were
      reported and compared in preoperative and six-month postoperative questionnaires.
      RESULTS: Almost 60% of women reported normal activity of daily life (ADL) within
      one week of surgery, irrespective of their age. Severe complications occurred in
      3% and were mainly intra-abdominal bleeding and vaginal vault hematomas. Six
      months postoperative, sexual activity had increased for 20% (p = 0.006) of women
      and urinary urgency was reduced for 50% (p = 0.001); however, 14% (n = 76) of
      women developed urinary incontinence, 76% (n = 58) of whom reported urinary
      stress incontinence. Patients were satisfied with the postoperative result in 93%
      of cases and 94% recommended the surgery. CONCLUSION: Vaginal hysterectomy is a
      patient-evaluated efficient treatment for uterovaginal prolapse with swift
      recovery and a low rate of complication. Sexual activity and symptoms of urinary
      urgency were improved. However, 14% developed incontinence, mainly urinary stress
      incontinence (11%). Therefore efforts to disclose latent stress incontinence
      should be undertaken preoperatively.

PMID- 19379513
TI  - Decreasing incidence of peptic ulcer complications after the introduction of the
      proton pump inhibitors, a study of the Swedish population from 1974-2002.
AB  - BACKGROUND: Despite a decreasing incidence of peptic ulcer disease, most previous
      studies report a stabile incidence of ulcer complications. We wanted to
      investigate the incidence of peptic ulcer complications in Sweden before and
      after the introduction of the proton pump inhibitors (PPI) in 1988 and compare
      these data to the sales of non-steroid anti-inflammatory drugs (NSAID) and
      acetylsalicylic acid (ASA). METHODS: All cases of gastric and duodenal ulcer
      complications diagnosed in Sweden from 1974 to 2002 were identified using the
      National hospital discharge register. Information on sales of ASA/NSAID was
      obtained from the National prescription survey. RESULTS: When comparing the time
      periods before and after 1988 we found a significantly lower incidence of peptic
      ulcer complications during the later period for both sexes (p < 0.001). Incidence
      rates varied from 1.5 to 7.8/100000 inhabitants/year regarding perforated peptic
      ulcers and from 5.2 to 40.2 regarding peptic ulcer bleeding. The number of sold
      daily dosages of prescribed NSAID/ASA tripled from 1975 to 2002. The number of
      prescribed sales to women was higher than to males. Sales of low-dose ASA also
      increased. The total volume of NSAID and ASA, i.e. over the counter sale and sold
      on prescription, increased by 28% during the same period. CONCLUSION: When
      comparing the periods before and after the introduction of the proton pump
      inhibitors we found a significant decrease in the incidence of peptic ulcer
      complications in the Swedish population after 1988 when PPI were introduced on
      the market. The cause of this decrease is most likely multifactorial, including
      smoking habits, NSAID consumption, prevalence of Helicobacter pylori and the
      introduction of PPI. Sales of prescribed NSAID/ASA increased, especially in
      middle-aged and elderly women. This fact seems to have had little effect on the
      incidence of peptic ulcer complications.

PMID- 19379515
TI  - CYP17, GSTP1, PON1 and GLO1 gene polymorphisms as risk factors for breast cancer:
      an Italian case-control study.
AB  - BACKGROUND: Estrogens, environmental chemicals with carcinogenic potential, as
      well as oxidative and carbonyl stresses play a very important role in breast
      cancer (BC) genesis and progression. Therefore, polymorphisms of genes encoding
      enzymes involved in estrogen biosynthesis pathway and in the metabolic activation
      of pro-carcinogens to genotoxic intermediates, such as cytochrome P450C17alpha
      (CYP17), endogenous free-radical scavenging systems, such as glutathione S
      transferase (GSTP1) and paraoxonase 1 (PON1), and anti-glycation defenses, such
      as glyoxalase I (GLO1), could influence individual susceptibility to BC. In the
      present case-control study, we investigated the possible association of CYP17
      A1A2, GSTP1 ILE105VAL, PON1 Q192R or L55M, and GLO1 A111E polymorphisms with the
      risk of BC. METHODS: The above-said five polymorphisms were characterized in 547
      patients with BC and in 544 healthy controls by PCR/RFLP methods, using DNA from
      whole blood. To estimate the relative risks, Odds ratios and 95% confidence
      intervals were calculated using unconditional logistic regression after adjusting
      for the known risk factors for BC. RESULTS: CYP17 polymorphism had no major
      effect in BC proneness in the overall population. However, it modified the risk
      of BC for certain subgroups of patients. In particular, among premenopausal women
      with the A1A1 genotype, a protective effect of later age at menarche and parity
      was observed. As to GSTP1 and PON1 192 polymorphisms, the mutant Val and R
      alleles, respectively, were associated with a decreased risk of developing BC,
      while polymorphisms in PON1 55 and GLO1 were associated with an increased risk of
      this neoplasia. However, these findings, while nominally significant, did not
      withstand correction for multiple testing. CONCLUSION: Genetic polymorphisms in
      biotransformation enzymes CYP17, GSTP1, PON1 and GLO1 could be associated with
      the risk for BC. Although significances did not withstand correction for multiple
      testing, the results of our exploratory analysis warrant further studies on the
      above mentioned genes and BC.

PMID- 19379516
TI  - Differential gene expression in the salivary gland during development and onset
      of xerostomia in Sjogren's syndrome-like disease of the C57BL/6.NOD-Aec1Aec2
      mouse.
AB  - INTRODUCTION: Recently, we reported the development of the C57BL/6.NOD-Aec1Aec2
      mouse that carries two genetic intervals derived from the non-obese diabetic
      (NOD) mouse capable of conferring Sjogren's syndrome (SjS)-like disease in SjS
      non-susceptible C57BL/6 mice. In an attempt to define the molecular bases
      underlying the onset of stomatitis sicca (xerostomia) in this C57BL/6.NOD
      Aec1Aec2 mouse model, we have carried out a study using genomic microarray
      technology. METHODS: By means of oligonucleotide microarrays, gene expression
      profiles of salivary glands at 4, 8, 12, 16, and 20 weeks of age were generated
      for C57BL/6.NOD-Aec1Aec2 male mice. Using Linear Models for Microarray Analysis
      and B-statistics software, 480 genes were identified as being differentially
      expressed (P < 0.01 and Q < 0.0001) during the development of SjS-like disease in
      the salivary glands. RESULTS: The 480 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
      biological functions. By means of pair-wise analysis, temporal changes in
      transcript expressions provided profiles indicating that many additional genes
      are differentially expressed at specific time points during the development of
      disease. Multiple genes reportedly showing an association with autoimmunity
      and/or SjS, in either humans or mouse models, were found to exhibit differential
      expressions, both quantitatively and temporally. Selecting various families of
      genes associated with specific functions (for example, antibody production,
      complement, and chemokines), we noted that only a limited number of family
      members showed differential expressions and these correlated with specific phases
      of disease. CONCLUSIONS: Taking advantage of known functions of these genes,
      investigators can construct interactive gene pathways, leading to modeling of
      possible underlying events inducing salivary gland dysfunction. Thus, these
      different approaches to analyzing microarray data permit the 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.

PMID- 19379518
TI  - Development of a fingerprinting panel using medically relevant polymorphisms.
AB  - BACKGROUND: For population based biorepositories to be of use, rigorous quality
      control and assurance must be maintained. We have designed and validated a panel
      of polymorphisms for individual sample identification consisting of 36 common
      polymorphisms that have been implicated in a wide range of diseases and an
      additional sex marker. This panel uniquely identifies our biorepository of
      approximately 20,000 samples and would continue to uniquely identify samples in
      biorepositories of over 100 million samples. METHODS: A panel of polymorphisms
      associated with at least one disease state in multiple populations was
      constructed using a cut-off of 0.20 or greater confirmed minor allele frequency
      in a European Caucasian population. The fingerprinting assay was tested using the
      MALDI-TOF mass spectrometry method of allele determination on a Sequenom platform
      with a panel of 28 Caucasian HapMap samples; the results were compared with known
      genotypes to ensure accuracy. The frequencies of the alleles were compared to the
      expected frequencies from dbSNP and any genotype that did not achieve Hardy
      Weinberg equilibrium was excluded from the final assay. RESULTS: The final assay
      consisted of the AMG sex marker and 36 medically relevant polymorphisms with
      representation on each chromosome, encompassing polymorphisms on both the
      Illumina 550K bead array and the Affymetrix 6.0 chip (with over a million
      polymorphisms) platform. The validated assay has a P(ID) of 6.132 x 10(-15) and a
      Psib(ID) of 3.077 x 10(-8). This assay allows unique identification of our
      biorepository of 20,000 individuals as well and ensures that as we continue to
      recruit individuals they can be uniquely fingerprinted. In addition, diseases
      such as cancer, heart disease diabetes, obesity, and respiratory disease are well
      represented in the fingerprinting assay. CONCLUSION: The polymorphisms in this
      panel are currently represented on a number of common genotyping platforms making
      QA/QC flexible enough to accommodate a large number of studies. In addition, this
      panel can serve as a resource for investigators who are interested in the effects
      of disease in a population, particularly for common diseases.

PMID- 19379517
TI  - Rationale and design: telepsychology service delivery for depressed elderly
      veterans.
AB  - BACKGROUND: Older adults who live in rural areas experience significant
      disparities in health status and access to mental health care. "Telepsychology,"
      (also referred to as "telepsychiatry," or "telemental health") represents a
      potential strategy towards addressing this longstanding problem. Older adults may
      benefit from telepsychology due to its: (1) utility to address existing
      problematic access to care for rural residents; (2) capacity to reduce stigma
      associated with traditional mental health care; and (3) utility to overcome
      significant age-related problems in ambulation and transportation. Moreover,
      preliminary evidence indicates that telepsychiatry programs are often less
      expensive for patients, and reduce travel time, travel costs, and time off from
      work. Thus, telepsychology may provide a cost-efficient solution to access-to
      care problems in rural areas. METHODS: We describe an ongoing four-year
      prospective, randomized clinical trial comparing the effectiveness of an
      empirically supported treatment for major depressive disorder, Behavioral
      Activation, delivered either via in-home videoconferencing technology
      ("Telepsychology") or traditional face-to-face services ("Same-Room"). Our
      hypothesis is that in-homeTelepsychology service delivery will be equally
      effective as the traditional mode (Same-Room). Two-hundred twenty-four (224) male
      and female elderly participants will be administered protocol-driven individual
      Behavioral Activation therapy for depression over an 8-week period; and subjects
      will be followed for 12-months to ascertain longer-term effects of the treatment
      on three outcomes domains: (1) clinical outcomes (symptom severity, social
      functioning); (2) process variables (patient satisfaction, treatment credibility,
      attendance, adherence, dropout); and (3) economic outcomes (cost and resource
      use). DISCUSSION: Results from the proposed study will provide important insight
      into whether telepsychology service delivery is as effective as the traditional
      mode of service delivery, defined in terms of clinical, process, and economic
      outcomes, for elderly patients with depression residing in rural areas without
      adequate access to mental health services. TRIAL REGISTRATION: National
      Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier#
      NCT00324701).

PMID- 19379519
TI  - Thermal behaviour of Anopheles stephensi in response to infection with malaria
      and fungal entomopathogens.
AB  - BACKGROUND: Temperature is a critical determinant of the development of malaria
      parasites in mosquitoes, and hence the geographic distribution of malaria risk,
      but little is known about the thermal preferences of Anopheles. A number of other
      insects modify their thermal behaviour in response to infection. These
      alterations can be beneficial for the insect or for the infectious agent. Given
      current interest in developing fungal biopesticides for control of mosquitoes,
      Anopheles stephensi were examined to test whether mosquitoes showed thermally
      mediated behaviour in response to infection with fungal entomopathogens and the
      rodent malaria, Plasmodium yoelii. METHODS: Over two experiments, groups of An.
      stephensi were infected with one of three entomopathogenic fungi, and/or P.
      yoelii. Infected and uninfected mosquitoes were released on to a thermal gradient
      (14 - 38 degrees C) for "snapshot" assessments of thermal preference during the
      first five days post-infection. Mosquito survival was monitored for eight days
      and, where appropriate, oocyst prevalence and intensity was assessed. RESULTS AND
      CONCLUSION: Both infected and uninfected An. stephensi showed a non-random
      distribution on the gradient, indicating some capacity to behaviourally
      thermoregulate. However, chosen resting temperatures were not altered by any of
      the infections. There is thus no evidence that thermally-mediated behaviours play
      a role in determining malaria prevalence or that they will influence the
      performance of fungal biopesticides against adult Anopheles.

PMID- 19379521
TI  - Amphioxus encodes the largest known family of green fluorescent proteins, which
      have diversified into distinct functional classes.
AB  - BACKGROUND: Green fluorescent protein (GFP) has been found in a wide range of
      Cnidaria, a basal group of metazoans in which it is associated with pigmentation,
      fluorescence, and light absorbance. A GFP has been recently discovered in the
      pigmentless chordate Branchiostoma floridae (amphioxus) that shows intense
      fluorescence mainly in the head region. RESULTS: The amphioxus genome encodes 16
      closely-related GFP-like proteins, all of which appear to be under purifying
      selection. We divide them into 6 clades based on protein sequence identity and
      show that representatives of each clade have significant differences in
      fluorescence intensity, extinction coefficients, and absorption profiles.
      Furthermore, GFPs from two clades exhibit antioxidant capacity. We therefore
      propose that amphioxus GFPs have diversified their functions into fluorescence,
      redox, and perhaps just light absorption in relation to pigmentation and/or
      photoprotection. CONCLUSION: The rapid radiation of amphioxus GFP into clades
      with distinct functions and spectral properties reveals functional plasticity of
      the GFP core. The high sequence similarities between different clades provide a
      model system to map sequence variation to functional changes, to better
      understand and engineer GFP.

PMID- 19379520
TI  - The effect of comorbidity on the use of adjuvant chemotherapy and survival from
      colon cancer: a retrospective cohort study.
AB  - BACKGROUND: Comorbidity has a well documented detrimental effect on cancer
      survival. However it is difficult to disentangle the direct effects of
      comorbidity on survival from indirect effects via the influence of comorbidity on
      treatment choice. This study aimed to assess the impact of comorbidity on colon
      cancer patient survival, the effect of comorbidity on treatment choices for these
      patients, and the impact of this on survival among those with comorbidity.
      METHODS: This retrospective cohort study reviewed 589 New Zealanders diagnosed
      with colon cancer in 1996-2003, followed until the end of 2005. Clinical and
      outcome data were obtained from clinical records and the national mortality
      database. Cox proportional hazards and logistic regression models were used to
      assess the impact of comorbidity on cancer specific and all-cause survival, the
      effect of comorbidity on chemotherapy recommendations for stage III patients, and
      the impact of this on survival among those with comorbidity. RESULTS: After
      adjusting for age, sex, ethnicity, area deprivation, smoking, stage, grade and
      site of disease, higher Charlson comorbidity score was associated with poorer all
      cause survival (HR = 2.63 95%CI:1.82-3.81 for Charlson score > or = 3 compared
      with 0). Comorbidity count and several individual conditions were significantly
      related to poorer all-cause survival. A similar, but less marked effect was seen
      for cancer specific survival. Among patients with stage III colon cancer, those
      with a Charlson score > or = 3 compared with 0 were less likely to be offered
      chemotherapy (19% compared with 84%) despite such therapy being associated with
      around a 60% reduction in excess mortality for both all-cause and cancer specific
      survival in these patients. CONCLUSION: Comorbidity impacts on colon cancer
      survival thorough both physiological burden of disease and its impact on
      treatment choices. Some patients with comorbidity may forego chemotherapy
      unnecessarily, increasing avoidable cancer mortality.

PMID- 19379522
TI  - Complete mitochondrial genome of Bugula neritina (Bryozoa, Gymnolaemata,
      Cheilostomata): phylogenetic position of Bryozoa and phylogeny of lophophorates
      within the Lophotrochozoa.
AB  - BACKGROUND: The phylogenetic position of Bryozoa is one of the most controversial
      issues in metazoan phylogeny. In an attempt to address this issue, the first
      bryozoan mitochondrial genome from Flustrellidra hispida (Gymnolaemata,
      Ctenostomata) was recently sequenced and characterized. Unfortunately, it has
      extensive gene translocation and extremely reduced size. In addition, the
      phylogenies obtained from the result were conflicting, so they failed to assign a
      reliable phylogenetic position to Bryozoa or to clarify lophophorate phylogeny.
      Thus, it is necessary to characterize further mitochondrial genomes from slowly
      evolving bryozoans to obtain a more credible lophophorate phylogeny. RESULTS: The
      complete mitochondrial genome (15,433 bp) of Bugula neritina (Bryozoa,
      Gymnolaemata, Cheilostomata), one of the most widely distributed cheliostome
      bryozoans, is sequenced. This second bryozoan mitochondrial genome contains the
      set of 37 components generally observed in other metazoans, differing from that
      of F. hispida (Bryozoa, Gymnolaemata, Ctenostomata), which has only 36 components
      with loss of tRNAser(ucn) genes. The B. neritina mitochondrial genome possesses
      27 multiple noncoding regions. The gene order is more similar to those of the two
      remaining lophophorate phyla (Brachiopoda and Phoronida) and a chiton Katharina
      tunicate than to that of F. hispida. Phylogenetic analyses based on the
      nucleotide sequences or amino acid residues of 12 protein-coding genes showed
      consistently that, within the Lophotrochozoa, the monophyly of the bryozoan class
      Gymnolaemata (B. neritina and F. hispida) was strongly supported and the bryozoan
      clade was grouped with brachiopods. Echiura appeared as a subtaxon of Annelida,
      and Entoprocta as a sister taxon of Phoronida. The clade of Bryozoa + Brachiopoda
      was clustered with either the clade of Annelida-Echiura or that of Phoronida +
      Entoprocta. CONCLUSION: This study presents the complete mitochondrial genome of
      a cheliostome bryozoan, B. neritina. The phylogenetic analyses suggest a close
      relationship between Bryozoa and Brachiopoda within the Lophotrochozoa. However,
      the sister group of Bryozoa + Brachiopoda is still ambiguous, although it has
      some attractions with Annelida-Echiura or Phoronida + Entoprocta. If the latter
      is a true phylogeny, lophophorate monophyly including Entoprocta is supported.
      Consequently, the present results imply that Brachiozoa (= Brachiopoda +
      Phoronida) and the recently-resurrected Bryozoa concept comprising Ectoprocta and
      Entoprocta may be refuted.

PMID- 19379523
TI  - POINeT: protein interactome with sub-network analysis and hub prioritization.
AB  - BACKGROUND: Protein-protein interactions (PPIs) are critical to every aspect of
      biological processes. Expansion of all PPIs from a set of given queries often
      results in a complex PPI network lacking spatiotemporal consideration. Moreover,
      the reliability of available PPI resources, which consist of low- and high
      throughput data, for network construction remains a significant challenge. Even
      though a number of software tools are available to facilitate PPI network
      analysis, an integrated tool is crucial to alleviate the burden on querying
      across multiple web servers and software tools. RESULTS: We have constructed an
      integrated web service, POINeT, to simplify the process of PPI searching,
      analysis, and visualization. POINeT merges PPI and tissue-specific expression
      data from multiple resources. The tissue-specific PPIs and the numbers of
      research papers supporting the PPIs can be filtered with user-adjustable
      threshold values and are dynamically updated in the viewer. The network
      constructed in POINeT can be readily analyzed with, for example, the built-in
      centrality calculation module and an integrated network viewer. Nodes in global
      networks can also be ranked and filtered using various network analysis formulas,
      i.e., centralities. To prioritize the sub-network, we developed a ranking
      filtered method (S3) to uncover potential novel mediators in the midbody network.
      Several examples are provided to illustrate the functionality of POINeT. The
      network constructed from four schizophrenia risk markers suggests that EXOC4
      might be a novel marker for this disease. Finally, a liver-specific PPI network
      has been filtered with adult and fetal liver expression profiles. CONCLUSION: The
      functionalities provided by POINeT are highly improved compared to previous
      version of POINT. POINeT enables the identification and ranking of potential
      novel genes involved in a sub-network. Combining with tissue-specific gene
      expression profiles, PPIs specific to selected tissues can be revealed. The
      straightforward interface of POINeT makes PPI search and analysis just a few
      clicks away. The modular design permits further functional enhancement without
      hampering the simplicity. POINeT is available at
      (http://poinet.bioinformatics.tw/).

PMID- 19379524
TI  - Age distribution and gender differences in psychogenic fever patients.
AB  - Psychogenic fever is one of the most common psychosomatic diseases. In Japan,
      psychogenic fever has generally been reported to occur in adolescents, with a
      peak seen at age 13. However, in our department we have encountered many adults
      with psychogenic fever. Therefore, we investigated all outpatients who visited
      the Psychosomatic Department of the University of Occupational and Environmental
      Health between April 2003 and March 2007. Of the 2705 outpatients that were seen,
      55 patients (2.0%) were diagnosed with psychogenic fever. The patients ranged in
      age from 11 to 82 years old, with a mean age of 33.6 +/- 17.9 (mean +/- SD)
      years. In addition to the adolescents, many of the patients were in their 20 s
      and 30 s, and the male:female ratio was 1:2.2. This study suggests that
      psychogenic fever commonly occurs not only in adolescents but also in adults.

PMID- 19379525
TI  - Intramucosal adenocarcinoma of the ileum originated 40 years after
      ileosigmoidostomy.
AB  - BACKGROUND: Small bowel adenocarcinomas (SBAs) are rare carcinomas. They are
      asymptomatic and usually neither endoscopy nor contrast studies are performed for
      screening CASE PRESENTATION: A 72-year-old Japanese male had a positive fecal
      occult blood test at a regular check-up in 2006. He suffered appendicitis and
      received an ileosigmoidostomy in 1966. A colonoscopy revealed an irregular
      mucosal lesion with an unclear margin at the ileum side of the anastomosis. A
      mucosal biopsy specimen showed adenocarcinoma histopathologically. Excision of
      the anastomosis was performed for this patient. The resected specimen showed a
      flat mucosal lesion with a slight depression at the ileum adjacent to the
      anastomosis. Histological examination revealed a well differentiated intramucosal
      adenocarcinoma (adenocarcinoma in situ). Immunohistological staining demonstrated
      the overexpression of p53 protein in the adenocarcinoma. CONCLUSION:
      Adenocarcinoma of the ileum at such an early stage is a very rare event. In this
      case, there is a possibility that the ileosigmoidostomy resulted in a back flow
      of colonic stool to the ileum that caused the carcinogenesis of the small
      intestine.

PMID- 19379526
TI  - CO2 assimilation, ribulose-1,5-bisphosphate carboxylase/oxygenase, carbohydrates
      and photosynthetic electron transport probed by the JIP-test, of tea leaves in
      response to phosphorus supply.
AB  - BACKGROUND: Although the effects of P deficiency on tea (Camellia sinensis (L.)
      O. Kuntze) growth, P uptake and utilization as well as leaf gas exchange and Chl
      a fluorescence have been investigated, very little is known about the effects of
      P deficiency on photosynthetic electron transport, photosynthetic enzymes and
      carbohydrates of tea leaves. In this study, own-rooted 10-month-old tea trees
      were supplied three times weekly for 17 weeks with 500 mL of nutrient solution at
      a P concentration of 0, 40, 80, 160, 400 or 1000 microM. This objective of this
      study was to determine how P deficiency affects CO2 assimilation, Rubisco,
      carbohydrates and photosynthetic electron transport in tea leaves to understand
      the mechanism by which P deficiency leads to a decrease in CO2 assimilation.
      RESULTS: Both root and shoot dry weight increased as P supply increased from 0 to
      160 microM, then remained unchanged. P-deficient leaves from 0 to 80 muM P
      treated trees showed decreased CO2 assimilation and stomatal conductance, but
      increased intercellular CO2 concentration. Both initial and total Rubisco
      activity, contents of Chl and total soluble protein in P-deficient leaves
      decreased to a lesser extent than CO2 assimilation. Contents of sucrose and
      starch were decreased in P-deficient leaves, whereas contents of glucose and
      fructose did not change significantly except for a significant increase in the
      lowest P leaves. OJIP transients from P-deficient leaves displayed a rise at the
      O-step and a depression at the P-step, accompanied by two new steps at about 150
      mus (L-step) and at about 300 mus (K-step). RC/CSo, TRo/ABS (or Fv/Fm), ETo/ABS,
      REo/ABS, maximum amplitude of IP phase, PIabs and PItot, abs were decreased in P
      deficient leaves, while VJ, VI and dissipated energy were increased. CONCLUSION:
      P deficiency decreased photosynthetic electron transport capacity by impairing
      the whole electron transport chain from the PSII donor side up to the PSI, thus
      decreasing ATP content which limits RuBP regeneration, and hence, the rate of CO2
      assimilation. Energy dissipation is enhanced to protect P-deficient leaves from
      photo-oxidative damage in high light.

PMID- 19379527
TI  - Exhaled nitric oxide in a population-based study of southern California
      schoolchildren.
AB  - BACKGROUND: Determinants of exhaled nitric oxide (FeNO) need to be understood
      better to maximize the value of FeNO measurement in clinical practice and
      research. Our aim was to identify significant predictors of FeNO in an initial
      cross-sectional survey of southern California schoolchildren, part of a larger
      longitudinal study of asthma incidence. METHODS: During one school year, we
      measured FeNO at 100 ml/sec flow, using a validated offline technique, in 2568
      children of age 7-10 yr. We estimated online (50 ml/sec flow) FeNO using a
      prediction equation from a separate smaller study with adjustment for offline
      measurement artifacts, and analyzed its relationship to clinical and demographic
      characteristics. RESULTS: FeNO was lognormally distributed with geometric means
      ranging from 11 ppb in children without atopy or asthma to 16 ppb in children
      with allergic asthma. Although effects of atopy and asthma were highly
      significant, ranges of FeNO for children with and without those conditions
      overlapped substantially. FeNO was significantly higher in subjects aged > 9,
      compared to younger subjects. Asian-American boys showed significantly higher
      FeNO than children of all other sex/ethnic groups; Hispanics and African
      Americans of both sexes averaged slightly higher than non-Hispanic whites.
      Increasing height-for-age had no significant effect, but increasing weight-for
      height was associated with decreasing FeNO. CONCLUSION: FeNO measured offline is
      a useful biomarker for airway inflammation in large population-based studies.
      Further investigation of age, ethnicity, body-size, and genetic influences is
      needed, since they may contribute to substantial variation in FeNO.

PMID- 19379528
TI  - Most parsimonious haplotype allele sharing determination.
AB  - BACKGROUND: The "common disease--common variant" hypothesis and genome-wide
      association studies have achieved numerous successes in the last three years,
      particularly in genetic mapping in human diseases. Nevertheless, the power of the
      association study methods are still low, in particular on quantitative traits,
      and the description of the full allelic spectrum is deemed still far from reach.
      Given increasing density of single nucleotide polymorphisms available and
      suggested by the block-like structure of the human genome, a popular and
      prosperous strategy is to use haplotypes to try to capture the correlation
      structure of SNPs in regions of little recombination. The key to the success of
      this strategy is thus the ability to unambiguously determine the haplotype allele
      sharing status among the members. The association studies based on haplotype
      sharing status would have significantly reduced degrees of freedom and be able to
      capture the combined effects of tightly linked causal variants. RESULTS: For
      pedigree genotype datasets of medium density of SNPs, we present two methods for
      haplotype allele sharing status determination among the pedigree members.
      Extensive simulation study showed that both methods performed nearly perfectly on
      breakpoint discovery, mutation haplotype allele discovery, and shared chromosomal
      region discovery. CONCLUSION: For pedigree genotype datasets, the haplotype
      allele sharing status among the members can be deterministically, efficiently,
      and accurately determined, even for very small pedigrees. Given their excellent
      performance, the presented haplotype allele sharing status determination programs
      can be useful in many downstream applications including haplotype based
      association studies.

PMID- 19379529
TI  - Evaluation sensitivity as a moderator of communication disorder in schizophrenia.
AB  - BACKGROUND: Communication disturbance (thought disorder) is a central feature of
      schizophrenia that predicts poor functioning. We investigated the hypothesis that
      memory and attention deficits interact with beliefs about the gravity of being
      rejected (i.e. evaluation sensitivity) to produce the symptoms of communication
      disorder. METHOD: Seventy-four individuals diagnosed with schizophrenia or schizo
      affective disorder completed a battery of tests assessing neurocognition
      (attention, working and verbal memory, abstraction), symptomatology (positive,
      negative and affective), functioning, and dysfunctional beliefs. RESULTS:
      Patients with communication deviance (n=33) performed more poorly on the
      neurocognitive tests and reported a greater degree of sensitivity to rejection
      than patients with no thought disorder (n=41). In a logistic regression analysis,
      evaluation sensitivity moderated the relationship between cognitive impairment
      and the presence of communication disorder. This finding was independent of
      hallucinations, delusions, negative symptoms, depression and anxiety.
      CONCLUSIONS: We propose that negative appraisals about acceptance instigate
      communication anomalies in individuals with a pre-existing diathesis for
      imperfect speech production.

PMID- 19379530
TI  - Patterns of co-morbidity of eating disorders and substance use in Swedish
      females.
AB  - BACKGROUND: Little is known about the association of eating disorder subtypes
      across multiple categories of substance use in population-based samples. We
      examined the association between eating disorders and substance use in a large
      population-based sample. METHOD: Female participants (n=13 297) were from the
      Swedish Twin Registry [Lichtenstein et al., Twin Research and Human Genetics
      (2006) 9, 875-882]. Substance use was examined in four defined groups - (1)
      anorexia nervosa (AN); (2) bulimia nervosa (BN); (3) AN and BN (ANBN); and (4)
      binge eating disorder (BED) as well as a referent group without eating disorder
      (no ED). Secondary analyses examined differences between restricting AN (RAN) and
      binge and/or purge AN (ANBP). RESULTS: In general, eating disorders were
      associated with greater substance use relative to the referent. The AN group had
      significantly increased odds for all illicit drugs. Significant differences
      emerged across the RAN and ANBP groups for alcohol abuse/dependence, diet pills,
      stimulants, and polysubstance use with greater use in the ANBP group. Across
      eating disorder groups, (1) the BN and ANBN groups were more likely to report
      alcohol abuse/dependence relative to the AN group, (2) the ANBN group was more
      likely to report diet pill use relative to the AN, BN and BED groups, and (3) the
      BN group was more likely to report diet pill use relative to the no ED, AN and
      BED groups. CONCLUSIONS: Eating disorders are associated with a range of
      substance use behaviors. Improved understanding of how they mutually influence
      risk could enhance understanding of etiology and prevention.

PMID- 19379531
TI  - Building consensus for moving forward.

PMID- 19379532
TI  - The denial of a psychosis epidemic.

PMID- 19379533
TI  - Brain volume changes in schizophrenia: how do they arise? What do they mean?

PMID- 19379534
TI  - Maladaptive mood repair responses distinguish young adults with early-onset
      depressive disorders and predict future depression outcomes.
AB  - BACKGROUND: Clinical depression involves persistent dysphoria, implicating
      impaired affect regulation or mood repair failure. However, there is
      comparatively little information about the mood repair repertoires of individuals
      with histories of clinical depression, how their repertories differ from that of
      never-depressed people, and whether particular types of mood repair responses
      differentially contribute to depression risk. METHOD: Adult probands who had
      childhood-onset depressive disorder (n=215) and controls with no history of major
      mental disorder (n=122) reported which specific (cognitive, behavioral,
      interpersonal and somatic-sensory) responses they typically deploy when
      experiencing sad affect, including responses known to appropriately attenuate
      dysphoria ('adaptive' responses) and those known to exacerbate dysphoria in the
      short or long run ('maladaptive' responses). Subjects were longitudinally
      followed and evaluated. RESULTS: Remitted probands and probands in depressive
      episodes both reported a greater number of maladaptive responses and fewer
      adaptive responses to their own sadness than did controls, although probands did
      not have an absolute deficiency of adaptive responses. Maladaptive (but not
      adaptive) mood repair responses predicted future increases in depression symptoms
      and an increased probability of a recurrent depressive episode among probands
      (even after controlling for several clinical predictors of course). Post-hoc
      analyses revealed that maladaptive non-cognitive and maladaptive cognitive mood
      repair response sets each predicted depression outcomes. CONCLUSIONS: Individuals
      with past and present episodes of depressive disorder report an array of
      cognitive and non-cognitive responses to their own sadness that are likely to
      exacerbate that affect, and this pattern predicts a worse course of the disorder.

PMID- 19379535
TI  - Mortality and cause of death among psychiatric patients: a 20-year case-register
      study in an area with a community-based system of care.
AB  - BACKGROUND: Most mortality studies of psychiatric patients published to date have
      been conducted in hospital-based systems of care. This paper describes a study of
      the causes of death and associated risk factors among psychiatric patients who
      were followed up over a 20-year period in an area where psychiatric care is
      entirely provided by community-based psychiatric services. METHOD: All subjects
      in contact with the South Verona Community-based Mental Health Service (CMHS)
      over a 20-year period with an ICD-10 psychiatric diagnosis were included. Of
      these 6956 patients, 938 died during the study period. Standardized mortality
      ratios (SMRs) and Poisson multiple regressions were used to assess the excess of
      mortality in the sample compared with the general population. RESULTS: The
      overall SMR of the psychiatric patients was 1.88. Mortality was significantly
      high among out-patients [SMR 1.71, 95% confidence interval (CI) 1.6-1.8], and
      higher still following the first admission (SMR 2.61, 95% CI 2.4-2.9). The SMR
      for infectious diseases was higher among younger patients and extremely high in
      patients with diagnoses of drug addiction (216.40, 95% CI 142.5-328.6) and
      personality disorders (20.87, 95% CI 5.2-83.4). CONCLUSIONS: This study found
      that psychiatric patients in contact with a CMHS have an almost twofold higher
      mortality rate than the general population. These findings demonstrate that,
      since the closure of long-stay psychiatric hospitals, the physical health care of
      people with mental health problems is often neglected and clearly requires
      greater attention by health-care policymakers, services and professionals.

PMID- 19379536
TI  - Diagnostic alterations for post-traumatic stress disorder: examining data from
      the National Comorbidity Survey Replication and National Survey of Adolescents.
AB  - BACKGROUND: Two alternative models of post-traumatic stress disorder (PTSD)
      appear to represent the disorder's latent structure better than the traditional
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) three
      factor PTSD model. The present study examines the impact of using these
      structural models for the diagnosis of lifetime PTSD while retaining the DSM-IV
      PTSD's six-symptom diagnostic requirement. METHOD: Data were gathered from large
      scale, epidemiological datasets collected with adults (National Comorbidity
      Survey Replication) and adolescents (National Survey of Adolescents). Two
      alternative, empirically supported four-factor models of PTSD were compared with
      the DSM-IV three-factor PTSD diagnostic model. RESULTS: Results indicated that
      the diagnostic alterations resulted in substantially improved structural
      validity, downward adjustments of PTSD's lifetime prevalence (roughly 1
      percentage point decreases in adults, 1-2.5 percentage point decreases in
      adolescents), and equivalent psychiatric co-morbidity and sociodemographic
      associations. CONCLUSIONS: Implications for modifying PTSD diagnostic criteria in
      future editions of DSM are discussed.

PMID- 19379537
TI  - Intensive practice of a cognitive task is associated with enhanced functional
      integration in schizophrenia.
AB  - BACKGROUND: There is increasing evidence that the frequently reported working
      memory impairments in schizophrenia might be partly due to an alteration in the
      functional connectivity between task-relevant areas. However, little is known
      about the functional connectivity patterns in schizophrenia patients during
      learning processes. In a previous study, Koch et al. [Neuroscience (2007) 146,
      1474-1483] have demonstrated stronger exponential activation decreases in
      schizophrenia patients during overlearning of short-term memory material. The
      question arises whether these differential temporal patterns of activation in
      schizophrenia patients and controls are going along with changes in task-related
      functional connectivity. METHOD: Therefore, in the current study, 13 patients
      with schizophrenia and 13 controls were studied while performing a short-term
      memory task associated with increasing overlearning of verbal stimulus material.
      Functional connectivity was investigated by analyses of psychophysiological
      interactions (PPI). RESULTS: Results revealed significant task-related modulation
      of functional connectivity between the left dorsolateral prefrontal cortex
      (DLPFC) and a network including the right DLPFC, left ventrolateral prefrontal
      cortex, premotor cortex, right inferior parietal cortex, left and right
      cerebellum as well as the left occipital lobe in patients during the course of
      overlearning and practice. No significant PPI results were detectable in
      controls. CONCLUSIONS: Activation changes with practice were associated with high
      functional connectivity between task-relevant areas in schizophrenia patients.
      This could be interpreted as a compensatory resource allocation and network
      integration in the context of cortical inefficiency and may be a specific
      neurophysiological signature underlying the pathophysiology of schizophrenia.

PMID- 19379538
TI  - Attitudes that determine willingness to seek psychiatric help for depression: a
      representative population survey applying the Theory of Planned Behaviour.
AB  - BACKGROUND: Many people suffering from mental disorders do not seek appropriate
      help. We have examined attitudes that further or hinder help-seeking for
      depression with an established socio-psychological model, the Theory of Planned
      Behaviour (TPB), comparing models for respondents with and without depressive
      symptoms. METHOD: A qualitative preparatory study (n=29) elicited salient
      behavioural (BB), normative (NB) and control beliefs (CB) that were later
      included in the TPB questionnaire. Telephone interviews with a representative
      population sample in Germany (n=2303) started with a labelled vignette describing
      symptoms of a major depression, followed by items covering the components of the
      TPB. Intention to see a psychiatrist for the problem described was elicited at
      the beginning and at the end of the interview. We screened participants for
      current depressive symptoms using the mood subscale of the Patient Health
      Questionnaire (PHQ-9). RESULTS: In non-depressed respondents (n=2167), a TPB path
      model predicted 42% of the variance for the first and 51% for the second question
      on intention. In an analogous model for depressed respondents (n=136), these
      values increased to 50% and 61% respectively. Path coefficients in both models
      were similar. In both depressed and non-depressed persons, attitude towards the
      behaviour was more important than the subjective norm, whereas perceived
      behavioural control was of minor influence. CONCLUSIONS: Willingness to seek
      psychiatric help for depression can largely be explained by a set of attitudes
      and beliefs as conceptualized by the TPB. Our findings suggest that changing
      attitudes in the general population are likely to effect help-seeking when people
      experience depressive symptoms.

PMID- 19379539
TI  - Outbreak of measles and rubella in refugee transit camps.
AB  - In 2004, concurrent measles and rubella outbreaks occurred in four camps hosting
      2767 Liberian refugees in Cote d'Ivoire. Sixty rash and fever cases were
      identified. From 19 January to 23 February 2004 (weeks 8-13), measles IgM testing
      showed that 61.1% were positive. The highest incidence rate (18.5%) of measles
      was observed in children aged <9 months. Ninety-three percent of children aged
      between 6 months and 15 years received a measles vaccine during week 13, but the
      rash and fever cases continued to occur. This prompted a systematic test for both
      measles and rubella IgM antibodies. Rubella IgM testing revealed 74.0% positive
      cases between 14 February and 25 April (weeks 11-21). The highest incidence rate
      (3.88%) of rubella was found in children aged between 5 and 15 years.
      Supplemental immunization with a measles-mumps-rubella (MMR) vaccine was
      conducted during week 20. This study illustrates the importance of testing for
      both measles and rubella in outbreaks of rash and fever in refugee settings.

PMID- 19379540
TI  - Is driving a car a risk for Legionnaires' disease?
AB  - Legionnaires' disease (LD) is a major cause of severe community-acquired
      pneumonia but the source and mode of transmission are not always apparent,
      especially in sporadic cases. We hypothesized that LD can be acquired from the
      air-conditioning systems of motor cars. Swabs were taken from the evaporator
      compartments of the air-conditioning system of scrapped cars. Healthy subjects
      who were mainly employees of regional transportation companies were tested for
      antibody to Legionella pneumophila serogroups 1-6; they also completed a
      questionnaire. Legionella species were detected in 11/22 scrapped cars by the
      loop-mediated isothermal amplification method. The prevalence of microplate
      agglutination titres > or =1:32 was significantly higher in subjects who
      sometimes used car air-conditioning systems. Although we did not prove a direct
      link between Legionella spp. in the car evaporator and LD, our findings point to
      a potential risk of car air-conditioning systems in LD, which needs further
      investigation.

PMID- 19379541
TI  - Prevalence of Bartonella infection in cats and dogs in a metropolitan area,
      Thailand.
AB  - The prevalence of Bartonella infection was studied in 312 cats and 350 dogs in
      the Bangkok metropolitan areas, Thailand, between June 2001 and February 2003.
      Bartonella was isolated from 47 (16.3%) of 288 stray cats, but from none of the
      24 pet cats studied. Of the 47 Bartonella-positive cats, 45 animals were infected
      with only B. henselae, one was infected with only B. clarridgeiae, and one with
      both B. henselae and B. clarridgeiae. 16S rRNA typing showed that 40 cats were
      infected with B. henselae type I, four with B. henselae type II, and one with
      both B. henselae types I and II. These results indicated that B. henselae,
      especially type I, was prevalent in stray cats that constituted a large
      Bartonella reservoir in Bangkok. B. clarridgeiae was isolated for the first time
      in Asia from one of 350 dogs.

PMID- 19379542
TI  - Comparison of the prevalence of bacterial enteropathogens, potentially zoonotic
      bacteria and bacterial resistance to antimicrobials in organic and conventional
      poultry, swine and beef production: a systematic review and meta-analysis.
AB  - The prevalences of zoonotic and potentially zoonotic bacteria or bacteria
      resistant to antimicrobials in organic and conventional poultry, swine and beef
      production were compared using systematic review and meta-analysis methodology.
      Thirty-eight articles were included in the review. The prevalence of
      Campylobacter was higher in organic broiler chickens at slaughter, but no
      difference in prevalence was observed in retail chicken. Campylobacter isolates
      from conventional retail chicken were more likely to be ciprofloxacin-resistant
      (odds ratio 9.62, 95% confidence interval 5.67-16.35). Bacteria isolated from
      conventional animal production exhibited a higher prevalence of resistance to
      antimicrobials; however, the recovery of some resistant strains was also
      identified in organic animal production, where there is an apparent reduced
      antimicrobial selection pressure. Limited or inconsistent research was identified
      in studies examining the prevalence of zoonotic and potentially zoonotic bacteria
      in other food-animal species. There is a need for further research of sufficient
      quality in this area.

PMID- 19379543
TI  - Human Dirofilaria repens infection in Serbia.
AB  - Human infection by Dirofilaria repens in Serbia has been increasing steadily. The
      first case was reported in 1971, presented in the form of a single subcutaneous
      nodule on the back of a young boy. As established by a literature search, eight
      additional cases were reported until mid-2001. The most frequent site of
      infection was subcutaneous tissue, with the exception of two cases, in which
      parasites were found in subconjunctiva and epididymis. Our study, conducted from
      2001 to 2008, encompasses 19 new cases. Most of them (63.1%) presented as ocular
      or periocular infections, in which the parasite was typically found under the
      conjunctiva. In other cases a parasitic nodule was localized in the temporal
      region of the head, epididymis, testicle, abdomen, breast or arm. The diagnosis
      was made by morphological and histological analysis of the extracted intact worms
      and parasite sections from the tissue. Morphology of the filarial worms was well
      preserved in more than half of the cases (12/19) and there was never more than
      one parasite found inside the lesions. Adult worms and immature nematodes were
      observed in nine and seven cases, respectively. Furthermore, in two cases
      microfilariae were discovered inside the pseudocoelom, sections of the female
      reproductive tubes filled with clearly visible larval stages. Dirofilaria repens
      infection was diagnosed by its morphological features (17/19) or by performing
      polymerase chain reactions (PCR) using paraffin-embedded tissues (2/19) in the
      cases where the morphology was insufficient for identification and the parasites
      had been determined initially as Dirofilaria spp. The amplified 246 bp PCR
      product showed that the worms were D. repens.

PMID- 19379544
TI  - New insights into the biology of filarial infections.
AB  - Recent successes in the control of lymphatic filariasis and onchocerciasis need
      continuing research in order to sustain the achievements and to develop further
      tools to tackle the new questions that arise when only reduced infection
      prevalences prevail. In this regard, in a symposium held at the Xth European
      Multicolloquium of Parasitology (August 2008, Paris) questions such as the impact
      of filarial immunosuppression, and its lack following filarial control, on the
      outcome of co-infections were addressed, as were new approaches to treatment with
      promising drugs such as moxidectin or the antibiotic chemotherapy against
      Wolbachia endosymbionts in filariae. In particular, longer treatment courses of
      doxycycline could be carried out by community-directed treatment at high
      coverage, thus potentially allowing its use in restricted areas with suboptimal
      responses to ivermectin against onchocerciasis, or in areas with co-infection by
      loiasis where onchocerciasis or lymphatic filariasis need to be controlled. New,
      more potent drugs, or eventually vaccines, will be of importance because in many
      vector-filarial parasite relationships worldwide, transmission efficacy increases
      with low numbers of ingested microfilariae, and since ivermectin may render
      treated hosts more susceptible to new infection.

PMID- 19379545
TI  - Food intake and prevalence of obesity in Brazil: an ecological analysis.
AB  - OBJECTIVE: To investigate the correlation between the consumption of refined
      carbohydrates and fats and the prevalence of obesity in the state capitals of
      Brazil. DESIGN: An ecological evaluation of obesity and dietary risk factors was
      carried out in twenty-six state capitals of Brazil. SETTING: Analysis was based
      on the age-standardized prevalence of obesity (BMI >or= 30.0 kg/m2) among adults
      aged 20-59 years. Both intake and obesity prevalence were obtained from the last
      National Family Household Budget Survey (HBS). The survey was conducted from July
      2002 to June 2003, based on a probabilistic national sample of 48 470 households.
      In each household, during seven consecutive days, all monetary and non-monetary
      expenses for food and beverages for family consumption were transformed into
      energy. The relative contribution of foods and food groups was expressed as the
      proportion (%) of total energy. Fruits and vegetables were also measured by the
      quantity bought in grams. RESULTS: Prevalence of obesity varied from 5.1 % to
      13.6 % among women and from 5.2 % to 17.6 % among men. For women, there were
      statistically significant correlations between obesity and intake of sugar and
      soft drinks (rS = 0.60; P = 0.001), ready-to-eat meals (rS = 0.39; P = 0.05) and
      potatoes (rS = 0.40; P = 0.04). For men there were no such associations.
      CONCLUSIONS: Increasing intake of refined carbohydrates, mainly soft drinks, may
      play a role in the prevalence of obesity among women in Brazil. Effecting changes
      in family purchase patterns may be a strategy to reduce obesity.

PMID- 19379546
TI  - Randomised, double-blinded, placebo-controlled, clinical trial of ozone therapy
      as treatment of sudden sensorineural hearing loss.

PMID- 19379547
TI  - [Detection of Bcr/Abl gene rearrangement in chronic myelogenous leukemia patients
      by dual-color dual-fusion fluorescence in situ hybridization].
AB  - This study was aimed to explore the value of dual-color dual-fusion fluorescence
      in situ hybridization (DC-DF-FISH) for the detection of bcr/abl fusion gene in
      chronic myeloid leukemia (CML). The karyotypes of chromosomes and bcr/abl fusion
      gene in 41 cases of CML including 18 cases of de-novo CML, 18 treated CML cases
      and 5 cases of CML received PBSCT were detected by conventional R-banding
      technique, DC-DF-FISH and RT-PCR. The results indicated that the Ph chromosome
      was found in 17 out of 18 cases of de novo CML by R-banding technique, with
      positive rate of 94.4%; DC-DF-FISH detection showed same result (94.4%). The R
      banding technique was adopted to detect 18 treated patients and showed that 14
      cases had metaphase for analysis, the Ph chromosome existed in 11 out of 14 cases
      with positive rate of 78.6% (11/14), however, DC-DF-FISH detection also showed
      positive rate of 94.4% (17/18) for these treated patients. The Ph chromosome in 5
      cases after PBSCT did not found by R-banding technique, meanwhile FISH detection
      indicated that 1 case had bcr/abl gene, RT-PCR assay confirmed the result of FISH
      detection. It is concluded that the DC-DF-FISH technique is an accurate and
      reliable method for detecting bcr/abl gene which can be used in diagnosis of CML,
      evaluation of therapeutic efficacy and detection of minimal residual disease.

PMID- 19379548
TI  - [Effect of silencing bmi-1 by RNA interference on function of K562 cell line].
AB  - Bmi-1 is a transcriptional repressor, which belongs to the polycomb group family.
      It has been demon- started that over-expression of Bmi-1 occurs in a variety of
      cancers, including several types of leukemia. Bmi-1 gene plays a key role in
      regulation of self-renewal in normal and leukemic stem cells. Acute myeloid
      leukemic cells lacking Bmi-1 undergo proliferation arrest and show signs of
      differentiation and apoptosis, which leads to the proposal of Bmi-1 as a
      potential target for therapeutic intervention in leukemia. The purpose of this
      study was to investigate the effect of short hairpin RNA (shRNA) targeting Bmi-1
      on functions of K562 cell line. The shRNA eukaryotic expression vector targeting
      Bmi-1 was constructed and transfected into K562 cells through lipofectamine 2000.
      The mRNA and protein levels of Bmi-1 were detected by PCR and Western blot
      respectively. The proliferation of K562 after Bmi-1 silencing was measured by
      using MTT assay and clone formation assay. The cell cycle was detected by flow
      cytometry. The results indicated that among the four shRNA designed, there was a
      shRNA which efficiently interfered with the expression of Bmi-1. The results of
      PCR and Western blot validated that the Bmi-1 gene of K562 cells transfected with
      such a Bmi-1 shRNA was suppressed successfully. Although levels of Bmi-1 mRNA and
      protein were significantly reduced, delivery of this siRNAs had no effect on cell
      viability or growth. Flow cytometry analysis suggested that Bmi-1 inhibition did
      not affect the cell cycle. It is concluded that the suppression of Bmi-1
      expression is not able to reduce proliferation of K562 cells, suggesting
      existence of some other parallel signaling pathways, which are fundamental for
      leukemic transformation and are independent of Bmi-1 over-expression. Bmi-1 over
      expression may play a secondary role in chronic myeloid leukemia transformation.

PMID- 19379549
TI  - [Relationship of immunophenotypic features with minimal residual disease
      detection and gene types in 221 cases of acute promyelocytic leukemia].
AB  - This study was aimed to investigate the relationship of immunophenotypic features
      with minimal residual disease (MRD) detection and gene types in APL patients.
      Immunophenotypes were analyzed in 221 newly diagnosed APL patients by using four
      color flow cytometry. Among of them, CD123 antibody was examined in 87 patients
      and the fused gene pml-raralpha were detected by PCR in 196 specimens
      simultaneously. The results of immunophenotyping demonstrated that the positive
      percentages of CD123, CD33 and CD9 in newly diagnosed APL patients were 100%,
      99.1% and 96.0% respectively, and mean percentages of positive cells in positive
      patients were all around 90%. Although the positive rates of CD117, CD13, CD38
      and CD64 were all above 96%, but the mean percentages of positive cells in
      different positive patients were diverse and average percentages of positive
      cells were about 70%. CD15, CD56 and CD11b were expressed in some patients, but
      CD34 and HLA-DR were rarely expressed in the majority of patients, and average
      positive percentages were all lower. Among 196 newly diagnosed APL patients,
      bcr1, bcr2 and bcr3 expressions were 63.3%, 4.6% and 32.1% respectively. The
      results showed a strong correlation of positive expression of CD34 with bcr3
      isoform. When cut-off value was chosen as 20%, the proportions of CD34 positive
      patients in bcr3 and bcr1 cases were 15.4% (10/65) and 3.3% (4/121) separately,
      which had a significant difference (p < 0.05). When cut-off value was 10%, bcr3
      cases had a significantly higher percentage of CD34 positive, compared with bcr1
      cases (p < 0.001), which was 47.7% (31/65) and 5.8% (7/121) respectively.
      However, there was no statistically significant difference on the other antigens
      between the two groups. Bcr3 isoform was highly indicated when CD34 was positive
      and non- large side scatter (NL-SSC) was shown in APL cells. It is concluded that
      there is a unique characteristics of immunophenotyping, and antigens such as
      CD123, CD33 and CD9 are more applicable to the detection of MRD in APL patients.
      The positive expression of CD34 and NL-SSC are associated with bcr3 isoform, and
      the relationship between gene type and antigen expression can be suggested more
      accurately when the cut-off value is chosen as 10%.

PMID- 19379550
TI  - [Role of mitochondria pathway in signal transduction of chronic myeloid
      leukemia].
AB  - This study was aimed to investigate the role of mitochondria pathway in signal
      transduction of chronic myeloid leukemia (CML). After bcr3/abl2 antisense
      oligodeoxynucleotide (ASO) was introduced into CML cell line K562 cells by
      liposomal transfection, the cell viability was detected by MTT assay, the cell
      apoptosis was determined by flow cytometry (FCM), the mitochondrial membrane
      potential (DeltaPsi) was labeled by Rhodamine 123 and examined by FCM, and the
      expression of mitochondrial apoptosis signal transduction pathway related
      proteins cytochrome C was analyzed by Western blot. The results showed that after
      K562 cells were exposed to 2 micromol/L of bcr3/abl2 ASO for 24 hours, bcr3/abl2
      ASO significantly inhibited cell viability with inhibitory rate of 65.7%, induced
      the apoptosis of K562 cell line with apoptotic rate of 16.9%, and decreased
      mitochondrial Deltapsi of K562 cells with the reducing rate of 38.33%, enhanced
      the expression of cytochrome C with increase of optical density value from 2.33
      +/- 0.3 to 4.78 +/- 0.1 by laser photometric scanning. It is concluded that
      mitochondria pathway plays an important role in signal transduction of chronic
      myeloid leukemia by directing apoptotic signal transduction.

PMID- 19379551
TI  - [Deletions of derivative chromosome 9 in 138 patients with chronic myeloid
      leukemia].
AB  - To investigate the frequency of derivative chromosome 9 [der (9)] deletions in
      patients with chronic myelogenous leukemia (CML), karyotype analysis in 138
      patients with CML was performed with R-banding technique, and dual fusion
      fluorescence in situ hybridization (FISH) was used to detect der (9) deletion.
      The results showed that among 138 cases, 126 cases were Ph positive (91.3%) from
      which 122 cases were typical Ph translocation, 12 cases were Ph negative (8.7%).
      FISH detection revealed 23 with der (9) deletions out of 138 cases (16.7%), 20
      out of 122 cases with typical Ph translocation showed typical Ph translocation
      (16.4%) and 3 out of 4 cases with variant Ph translocation had variant Ph
      translocation (75%). 20 cases were in chronic phase (CP) (17.2%), 3 cases were in
      blast crisis (BC) (17.6%), there was no significant difference in the frequency
      of the der (9) deletions between the cases in CP and in BC (p < 0.05). It is
      concluded that incidence of der (9) partial deletions in CML patients is 16.7%,
      FISH can effectively detect the der (9) deletions, and there is no correlation of
      der (9) deletion frequency between cases in different phases of CML.

PMID- 19379552
TI  - [Signal pathways of leukemia cell proliferation induced by ouabain].
AB  - The aim of this study was to investigate the effects of ouabain and some specific
      signal pathway inhibitors on growth regulation in various kinds of leukemia cell
      lines and to explore the role of signal pathways participating in proliferation
      or apoptosis of leukemia cells induced by ouabain. By using MTT, the survival
      rates of leukemia cell lines were observed after utilizing ouabain and the
      specific signal pathway inhibitors. The expressions of Na(+), K(+)-ATPase alpha1
      subunit of leukemia cells were evaluated by RT-PCR and Western blot. The results
      showed that low concentration of ouabain (10 nmol/L) could increase the survival
      rates of lymphocytic leukemia Jhhan cell line and megakaryocytic leukemia M07e
      cell line, and could up-regulate the expression of Na(+), K(+)-ATPase alpha1
      subunit. Proliferation of these leukemia cells induced by ouabain could be
      inhibited by PP2 and PD98059 with different extents. It is concluded that Na(+),
      K(+)-ATPase plays an important role in signal transductions through binding to
      CTS (ouabain), and they can activate complex signal pathways regulating the
      growth of leukemia cells. The proliferation effects of cells promoted by ouabain
      are mediated by activation of Src kinase and ERK1/2 dependent signaling pathway.

PMID- 19379553
TI  - [Bcl-6 expression in K562 cells and its role in mechanism underlying induced
      differentiation into various myelocytic lineages].
AB  - This study was purposed to investigate the changes of bcl-6 expression in K562
      cells and the mechanism inducing differentiation into different myelocyte
      lineages. Models of K562 cells inducing differentiation to lineages of
      megakaryocyte, erythrocyte and macrophagocyte were established with inducers TPA
      (tetradecanoylphorbol 13-acetate), Hu (hydroxyurea) and HMBA (hexamethylene
      bisacetamide) respectively. Western blot assay was applied to detect the
      expression of bcl-6 in K562 cells before and after the induction. Meanwhile, PCR,
      cloning and direct DNA sequencing were used to identify mutations in the 5'
      regulatory region of bcl-6 in K562 cells before and after induction with TPA. The
      results indicated that up-regulation of bcl-6 expression was found only in K562
      cells being induced differentiating into megakaryocyte-lineage, while mutation of
      5' regulatory region of bcl-6 gene was not found. It is concluded that expression
      of bcl-6 increases only when K562 cells differentiate into megakaryocyte lineage
      and bcl-6 expression may play an important role in K562 cells induced
      differentiation into megakaryocyte lineage. The up-regulation of bcl-6 expression
      may not be related with the mutation of 5' regulatory regions of the gene.

PMID- 19379554
TI  - [Analysis of NPM1 gene mutations in acute myeloid leukemia].
AB  - The aim of this study was to evaluate the nucleophosmin (NPM1) gene exon 12
      mutation in patients with acute myelogenous leukemia (AML) and its clinical
      characteristics. Genomic DNAs from 33 AML patients were amplified by PCR and
      sequencing for NPM1 mutations. The results showed that the NPM1 exon 12 mutations
      were found is 8 patients from 33 AML patients (24.2%) including 1 of M(1), 3 of
      M(2), 1 of M(4) and 3 of M(5). The NPM1 gene mutations were found in 7 out of 19
      patients with normal karyotype and their incidence was significantly higher than
      that in patients with karyotype abnormalities (1/14, 7.1%, p < 0.005). The
      proportion of bone marrow blast cells and the count of peripheral white blood
      cells in patients with NPMI exon 12 mutation were higher than that in patients
      with wild type NPMI gene. It is concluded that the occurrence of NPM1 exon 12
      mutations is observed more in AML patients with normal karyotype. NPM1 mutant
      cases are associated with more high amount of boon marrow blast cells and
      peripheral white blood cell count.

PMID- 19379555
TI  - [Expression of 5 genes in CD7 positive acute myeloid leukemia stem/progenitor
      cells from bone marrow].
AB  - This study was aimed to investigate abca5, mdr-1, kdr, dapk and irf-1 expressions
      in leukemia stem/progenitor cells (LSC) from CD7 positive acute myeloid leukemia,
      the expression of these 5 genes in mononuclear cells (MNC) from 15 normal bone
      marrow (NBM) and 16 AML patients bone marrow (AML BM) specimen were detected by
      real-time quantitative PCR (RQ-PCR). CD34(+)CD38(+) progenitor cells and
      CD34(+)CD38(-)Lin(-) stem cells were sorted by flow cytometry (FCM) from the MNCs
      of 10 NBM and 21 AML BM specimen. These 5 gene expressions in the sorted cells
      were detected by small amount cell RQ-PCR. The results showed that these 5 genes
      above mentioned all expressed in NBM-MNC, in which the expression levels of irf-1
      and dapk were highest with the relative expression levels 4.08 and 3.86, the
      expression levels of abca 5 and mdr-1 were in the middle with the relative
      expression 0.49 and 0.84 respectively, the kdr expression was lowest with the
      relative expression level 0.02. In CD34(+)CD38(+) progenitor cells, the
      expression level of kdr increased dramatically (p < 0.05) while irf-1 and dapk
      dramatically decreased (p < 0.05). There was no obvious change of expression in
      the rest 2 genes. In CD34(+)CD38(-) stem cells the expression level of these 5
      genes all increased nearly 2 times as much as that in CD34(+)CD38(+) progenitor
      cells, but kdr increased 3 times as much, and the increase of kdr and irf-1
      expressions was of statistical significance (p < 0.05). Compared with the NBM,
      expression levels of 5 genes in AML-MNC decreased, and out of them abca 5, mdr-1,
      kdr and dapk were decreased most remarkably (p < 0.05). Comparison between AML
      CD34(+)CD38(+) cells and AML MNC showed that the expression level of irf-1 and
      dapk were decreased dramatically (p < 0.05) while the rest 3 genes increased
      their expression with statistical significance (p < 0.05). The expression levels
      of these 5 genes were higher in CD34(+)CD38(-) cells than those in CD34(+)CD38(+)
      stem cells, and the increase of kdr and irf-1 expressions showed statistical
      difference (p < 0.05). These 5 genes expression levels were all higher than those
      in CD34(+)CD38(+) cells whether in AML CD34(+)CD38(-)CD7(+) cells or CD34(+)CD38(
      )CD7(-) cells. The increase of kdr expression in CD34(+)CD38(-)CD7(+) cells as
      well as kdr and irf-1 expressions in CD34(+)CD38(-)CD7(-) cells were all of
      statistical significance (p < 0.05). In conclusion the expression level of kdr in
      NBM was highest in stem cells while dapk and irf-1 were highest in differentiated
      cells. The expression levels of these 5 genes in CD34(+)CD38(-)Lin(-) stem cells
      were higher than those in CD34(+)CD38(+) progenitor cells. The gene expressions
      in AML CD34(+)CD38(-)CD7(+) cells and CD34(+)CD38(-)CD7(-) cells are in
      accordance with the characteristics of stem cells.

PMID- 19379556
TI  - [Beta-catenin and cyclin D1 mRNA levels in newly diagnosed patients with acute
      myeloid leukemia and their significance].
AB  - This study was aimed to quantitatively detect the levels of beta-catenin and
      cyclin D1 mRNA in various subgroups of acute myeloid leukemia (AML) and to
      analyze their potential relationship, so as to provide theoretical basis for
      exploring the role of Wnt/beta-catenin pathway in the pathogenesis of AML. Real
      time fluorescent quantitative RT-PCR was used to detect the relative expression
      levels of beta-catenin and cyclin D1 mRNA, to analyze changes of the two gene
      expressions and their relationship. The results showed that the beta-catenin mRNA
      expression level in BMMNC of AML patients was significantly higher than that in
      benign blood disease patients (p < 0.05), but no statistical difference was found
      among the various subgroups of AML (p > 0.05). In AML there was overexpression of
      cyclin D1 mRNA, and its expression level was significantly higher than that in
      benign blood disease group (p < 0.05), but there was no statistical difference
      among the subtypes of AML. The expression levels of beta-catenin and cyclin D1
      were correlated each other in AML-M(1), M(2) and M(4) (r values were 0.822,
      0.627, 0.712 respectively; p values were 0.001, 0.020, 0.002 respectively). It is
      concluded that the over-expressions of beta-catenin and cyclin D1 exit in AML
      patients, and the significant correlation appears in part of the subgroups, which
      means that the Wnt/beta-catenin pathway is aberrantly activated in AML, probably
      activating the downstream target gene cyclin D1 and participating in the
      regulation of cell cycle disturbance and abnormal proliferation of leukemic
      cells.

PMID- 19379557
TI  - [Effect of a methylation inhibitor 5-aza-2'-deoxycytidine on SHP-1 gene
      expression, proliferation and apoptosis in K562 cells].
AB  - The aim of this study was to investigate the regulation of 5-aza-CdR on
      transcription of SHP-1 gene and effects on the proliferation and apoptosis of
      K562 cells. Methylation-specific PCR (MSP) was used to detect CpG island
      methylation in SHP-1 promoter. MTT and flow cytometry were used to detect the
      growth and apoptosis of K562 cells after treatment with different concentration
      of 5-aza-CdR. The expressions of SHP-1 mRNA and protein were determined by FQ-PCR
      and Western blot. The expression of p-JAK2 was assayed by Western blot. The
      result showed that methylation of SHP-1 gene promoter was detected in K562 cells,
      and the SHP-1 mRNA and protein were expressed again in K562 cells after treatment
      with 5-aza-CdR, meanwhile the expression of phosphorylated P-JAK2 was down
      regulated; 5-aza-CdR significantly inhibited the cell growth in dose and time
      dependent manners. AG490 inhibited the cell proliferation. 5-aza-CdR increased
      the apoptosis rate of K562 cells also in dose- and time-dependent manners. The
      apoptosis rates of K562 cells treated with 5-aza-CdR for 1, 3 and 5 days were
      9.3%, 24.2% and 37.7% respectively. After treatment with 2 micromol/L 5-aza-CdR
      for 24 hours, cells in G(0)/G(1) phase increased gradually, cells in G(2)/M phase
      decreased gradually, cells were arrested in G(0)/G(1) phase. The cell ratios in
      G(2)/M phase at 1, 3 and 5 days after treatment with 5-aza-CdR were 30.7%, 23.45
      and 19.3% respectively. It is concluded that the 5-aza-CdR, inhibitor of specific
      methylation transferase, can re-express the silent SHP-1 gene in K562 cells,
      inhibits the proliferation of leukemia cells and induces cell apoptosis by
      activating JAK/STAT pathway.

PMID- 19379558
TI  - [Mechanism of leukemia cell apoptosis induced by sodium butyrate activating TRAIL
      pathway].
AB  - This study was aimed to investigate the mechanism of leukemia cell apoptosis
      induced by histone deacetylase inhibitor (HDACI). Flow cytometry was used to
      detect the apoptosis of leukemia cell lines NB4, U937 and Jurkat, and the changes
      of mRNA and protein expressions of TRAIL, DR4 and DR5 were detected by Western
      blot and RT-PCR respectively. The results showed that both TRAIL and DR5 protein
      and mRNA expressions in NB4, U937 and Jurkat cells increased after treated with
      sodium butyrate (SB) and in time-dependent manner. However, DR4 mRNA in leukemia
      cells was not significantly changed after treated with SB. It is concluded that
      the apoptosis mechanism of leukemic cell lines NB4, U937 and Jurkat induced by SB
      is closely related to the protein and mRNA expressions up-regulating TRAIL and
      DR5, but the DR4 may not participate in the apoptosis induced by SB.

PMID- 19379559
TI  - [Effects of silent nucleostemin gene expression on apoptosis of HL-60 cells in
      vitro].
AB  - This study was aimed to explore whether the apoptosis of leukemia cells can be
      induced by targeting silencing nucleostemin gene in vitro. HL-60 cells were taken
      as the model, and were directly transfected with nucleostemin short hairpin RNA
      (NS-shRNA). Sequences unrelated with NS gene were taken as control. The blocking
      effect of NS-shRNA was detected by RT-PCR, the morphology changes in living cells
      were observed under inverted microscope, and the changes of cell shape and
      nucleus were detected by Wright-Giemsa staining. The amount of apoptotic cells
      were assayed by flow cytometer (FCM) and TUNEL technique, and the positive rate
      of apoptosis was determined meanwhile. The results showed that two NS-shRNA were
      synthesized in vitro, and the more effective one was selected to be transfected
      into HL-60 cells. The blocking rate of NS-mRNA reached to 74.94%. After
      transfection for 48 hours, Wright-Giemsa staining showed nuclear fragmentations
      and "apoptosis body" in cells. The apoptosis rate in transfected group detected
      by flow cytometry and TUNEL method were (25.32 +/- 3.06)% and (27.3 +/- 3.21)%
      respectively, but were only (3.12 +/- 0.38)% and (3.30 +/- 1.52)% in control
      group, the difference between the transfected group and the control group was
      significant (p < 0.01). It is concluded that the apoptosis of HL-60 leukemia
      cells can be induced by the silencing NS gene expression in vitro, which provides
      a theoretical basis for using NS gene as a candidate target gene in therapy of
      malignant tumor.

PMID- 19379560
TI  - [Role of P27(Kip1) and TGF-beta1 in APL cell apoptosis induced by As(2)O(3)].
AB  - The aim of study was to investigate the effects of arsenic trioxide (As(2)O(3))
      on cell cycle and apoptosis of APL cells, as well as changes of P27(Kip1),
      endogenous TGF-beta1, cyclin E and bcl-2, and to explore the relationship between
      expression of P27(Kip1) and apoptosis induced by As(2)O(3). The apoptosis and
      cell cycle changes of APL cells treated with As(2)O(3) were detected by
      morphology and flow cytometry respectively, the protein and mRNA expressions of
      P27(Kip1), TGF-beta1, cyclin E and BCL-2 were measured by immunohistochemistry
      and RT-PCR. The results indicated that As(2)O(3) induced APL cell apoptosis in
      vitro, and cell cycle was arrested at G(1) phase. Apoptotic cells induced by
      As(2)O(3) 1, 5 and 10 micromol/L for 24 hours were 1.42%, 4.57% and 10.67%
      respectively; the proportion of apoptotic cells induced by As(2)O(3) of same
      concentrations for 48 hours increased to 8.92%, 16.07% and 18.90% respectively;
      the cells induced by As(2)O(3) for 72 hours were mainly in debris. Protein and
      mRNA expressions of P27(Kip1) and TGF-beta1 of APL cells after treatment with
      As(2)O(3) increased, accompanying with decrease of cyclin E, bcl-2 protein and
      mRNA expressions. Apoptotic cells were related to the expressions of P27(Kip1)
      (r(mRNA) = 0.55, p < 0.05) and TGF-beta1 (r(mRNA) = 0.51, p < 0.05). There was
      positive correlation between the expression of TGF-beta1 and of P27(Kip1)
      (r(mRNA) = 0.31, p < 0.05). It is concluded that the apoptosis of APL cells is
      induced by As(2)O(3), and the cell cycle is arrested at G(1) phase. The
      expression of P27(Kip1) is closely related to the extent of apoptosis induced by
      As(2)O(3). Apoptosis of APL cells induced by As(2)O(3) may be caused by up
      regulating TGF-beta1 and P27(Kip1), which is antagonistic to cyclin E and BLC-2,
      leading to arrest of cell cycle at G(1) phase.

PMID- 19379561
TI  - [Apoptosis of human myeloid leukemia cell line HL-60 cells induced by siRNA
      targeting gene c-myc].
AB  - This study was purposed to investigate the effects of siRNA targeting c-myc on
      apoptosis induction, proliferation in inhibition as well as c-myc protein and
      mRNA expression in human myeloid leukemia cell line HL-60 cells. C-myc siRNA
      synthesized in vitro was transfected into HL-60 cells by liposome. Changes of
      cell morphology were observed. Growth inhibition was detected by MTT assay and
      colony formation assay, and cell apoptosis was determined by DNA ladder. The
      expressions of c-myc mRNA and protein were detected by RT-PCR and Western-blot
      respectively. The results indicated that c-myc siRNA remarkably inhibited the
      cell proliferation, with an IC(50) value of 150 nmol/L. Data of DNA ladder showed
      that HL-60 cells apoptosis could be efficiently induced by c-myc siRNA, the
      apoptosis rate positively correlated with the time duration of treatment with
      drugs. The c-myc mRNA and protein expressions on HL-60 cells decreased after
      treatment with c-myc siRNA, which negatively correlated with time duration of
      treatment. It is concluded that c-myc siRNA can efficiently induce growth
      inhibition, decrease the expressions of c-myc mRNA and protein, and induce
      apoptosis in HL-60 cells.

PMID- 19379562
TI  - [Effects of 2-methoxyestradiol on the expression of caspase-3 and survivin in
      chronic myelocytic leukemia K562 cells].
AB  - The aim of this study was to investigate the effects of 2-methoxyestradiol (2-ME)
      on expressions of caspase-3 and survivin in chronic myelocytic leukemia (CML)
      K562 cells. The experiment was divided into 3 groups: control group, in which
      K562 cells were cultured in medium without 2-ME; the experimental group, in which
      K562 cells were cultured in medium containing different concentrations of 2-ME
      (1, 2, 4, 8 and 16 micromol/L) for 36 hours; the negative control group, in which
      K562 cells were replaced by distilled water without RNase in medium. The
      apoptosis rate, the protein and its mRNA expressions of caspase-3 and survivin of
      K562 cells was detected by TUNEL, flow cytometry (FCM), half-quantitative RT-PCR
      respectively. The results showed that the apoptosis rate of K562 cells in
      experimental group was significantly higher than that in control group (p <
      0.05). The apoptosis rate of K562 cells detected by FCM was almost the same as
      that detected by TUNEL method (p < 0.01). The result detected by TUNEL methods
      was positively correlated with that detected by FCM (gamma = 0.845, p = 0.034).
      The expression of caspase-3 protein increased in a concentration-dependent
      manner, and also this expression level in the experimental group was higher than
      that in the control group (p < 0.05); the expression of survivin protein
      decreased along with the increasing of 2-ME concentration. and the difference
      between the experimental group and the control group was statistically
      significant (p < 0.05). The expression of caspase-3 mRNA was higher in the
      experimental group than that in the control group (p < 0.01), and the expression
      of survivin mRNA was lower in the experimental group than that in the control
      group (p < 0.01). The expression level of caspase-3 mRNA was negatively
      correlated with that of survivin (gamma = -0.966, p = 0.001). It is concluded
      that the 2-ME can induce apoptosis of K562 cells in a concentration-dependent
      manner and indicate its promising potential in the treatment of CML patients.

PMID- 19379563
TI  - [Mechanism underlying 2-methoxyestradiol inducing apoptosis of K562 cells].
AB  - The aim of this study was to investigate apoptotic effect of 2-methoxyestradiol
      (2-ME2) on K562 cells and its mechanism. K562 cells were treated with different
      concentrations of 2-ME2. MTT assay was used to examine the effect inducing growth
      inhibition. DNA fragmentation assay and Annexin V-FITC/PI staining were used to
      detect the effect of apoptosis. The change of mitochondrial transmembrane
      potential was analyzed by flow cytometry. The expressions of related gene mRNA
      and/or proteins were detected by RT-PCR and Western blot respectively. The
      results indicated that the 2-ME2 inhibited proliferation of K562 cells in a time-
      and dose-dependent manners and the concentration of 50% growth inhibition
      (IC(50)) was 2 micromol/L at 48 hours. 2-ME2 induced DNA ladder and significantly
      increased apoptosis in K562 cells when exposed to 2 micromol/L of 2-ME2 for 24,
      48 and 72 hours, the result of Annexin-V/PI staining showed that rates of the
      apoptotic cells were 13.78%, 22.32% and 29.43% respectively, which was remarkably
      higher than that of control (1.78%) (p < 0.05). The FCM analysis showed that the
      mitochondrial transmembrane potential in K562 cells lowered after exposed to 1, 2
      and 4 micromol/L of 2-ME2 for 24 hours. 2-ME2 down-regulated the expression of
      bcr/abl and bcl-2, up-regulated the expression of bax mRNA, and down-regulated
      protein expressions of bcl-2, procaspase-3, procaspase-9, PARP (116 kD) and p
      Akt, and up-regulated expression of cytoplasmic Cyto-C and PARP 85 kD apoptosis
      related cleavage fragment protein, but had no effect on total Akt protein in K562
      cells after treated with 2 micromol/L of 2-ME2 for 24, 48 and 72 hours. It is
      concluded that the 2-ME2 can induce the apoptosis and inhibit the proliferation
      of K562 cells by increasing the ratio of bax/bcl-2, reducing the mitochondrial
      transmembrane potential, releasing cytochrome C to cytoplasm, initiating the
      mitochondrial apoptosis pathway and leading in turn to caspase-3 activation.
      These findings suggest that interfere PI3K/Akt signal pathway via down-regulating
      the expression of bcr/abl mRNA is implicated in the effect of 2-ME2 on K562
      cells.

PMID- 19379564
TI  - Daunorubicin-loaded magnetic nanoparticles of Fe(3)O(4) greatly enhance the
      responses of multidrug-resistant K562 leukemic cells in a nude mouse xenograft
      model to chemotherapy.
AB  - Multidrug resistance (MDR) plays a major role in the failure of cancer
      chemotherapy. Since Fe(3)O(4)-magnetic nanoparticle loaded with daunorubicin
      (DNR) can overcome multidrug-resistance of K562 cells in vitro, the effect of
      Fe(3)O(4)-magnetic nanoparticle loaded with DNR on multidrug-resistant K562 cells
      was studied in vivo, the K562-n and its MDR counterpart K562-n/VCR cells were
      inoculated subcutaneously into both sides of the back of nude mice to establish a
      human leukemia xenograft model. The mice were randomly divided into group A
      receiving normal saline, group B receiving DNR, group C receiving Fe(3)O(4)
      magnetic nanoparticle, group D receiving Fe(3)O(4)-magnetic nanoparticle loaded
      with DNR and group E receiving Fe(3)O(4)-magnetic nanoparticle containing DNR
      with a magnetic field built on the surface of the tumor tissue. The tumor volume
      was measured on the day 1, 5, 9, 13, 17 and 21 after the first treatment. Tumor
      tissues were isolated for examination of the expression of mdr-1 by reverse
      transcription polymerase chain reaction and Western blotting. The results showed
      that for K562-n/VCR tumor, the tumor volume was markedly lower in groups D and E
      than that in groups A, B and C. Pathological observation revealed that the tumor
      cells of group A and B grew well, some disseminated necrosis and some cells with
      karyorrhexis and karyopyknosis existed in group C. However, significant fracture,
      necrosis of cell and subsequently fibrosis were seen in group D and E. The
      transcription of mdr-1 gene in groups D and E was significantly lower than that
      in groups A, B and C (group D and E vs group A, B or C, p < 0.05). However, there
      were no differences about the protein expression of P-gp between these groups.
      The tumor volume of K562-n in groups C, D and E was markedly lower than that in
      groups A and B (group C, D and E vs group A or B, p < 0.05). Pathological
      observation showed that the tumor cell of group A and B grew well, and no obvious
      necrosis was observed. Significant fracture, necrosis of cell and subsequently
      fibrosis were seen in group C, D and E. It is concluded that DNR-loaded Fe(3)O(4)
      magnetic nanoparticles can suppress the growth of the MDR K562-n/VCR tumor in
      vivo, but can not further enhance its efficacy on the sensitive K562-n tumor as
      compared to DNR alone. The additional external magnetic field failed to further
      improve the antitumor effect in vivo.

PMID- 19379565
TI  - [Effect of phenylhexyl isothiocyanate on adriamycin resistance of K562/A02 cell
      line].
AB  - This study was to investigate the effect of phenylhexyl isothiocyanate (PHI) on
      drug resistance and sensitivity on K562/A02 cell line to adriamycin (ADM) and to
      elucidate the possible mechanisms. The inhibition rates of ADM and PHI + ADM on
      growth of K562/A02 cell line were measured by MTT assay, and K562/A02 cell
      resistant multiple was calculated. The apoptosis rate of K562/A02 cell line, the
      changes of intracellular ADM concentrations and MRP1 protein level were detected
      by flow cytometry (FCM). Intracellular reoxidized GSH level was determined by
      spectrometric enzyme assay and MRP1 mRNA was assayed by semiquantitative RT-PCR
      before and after using PHI. The results indicated that the survival rate of
      K562/A02 cell line decreased with the increasing concentration of PHI. Apoptosis
      rate increased after treatment in combination with two above drugs, the changes
      of drug resistance multiple and intracellular ADM level had statistical
      significance between K562/A02 and K562 cells (p < 0.05), when the concentration
      of PHI was more than 20 micromol/L. Intracellular GSH level in K562/A02 cell line
      reduced 5% when 1 microg/ml ADM was used alone, and it increased slightly at
      first, then decreased when more than 10 micromol/L PHI was used. When more than
      20 micromol/L PHI was used in combination with 1 microg/ml ADM, intracellular GSH
      level in K562/A02 cell line decreased progressively with increasing the
      concentration of PHI. The expressions of MRP1 mRNA and protein had no statistical
      significance between K562/A02 and K562 cells (p > 0.05) after or before PHI was
      used. It is concluded that the cyto-toxicity of PHI to K562/A02 cell line does
      not associate with the depletion of the intracellular GSH. PHI not only enhances
      the sensitivity of K562/A02 cell line to ADM, but also partially reverses effect
      of K562/A02 cell resistance to ADM. ADM combined with PHI can diminish side
      effect and dosage of ADM.

PMID- 19379566
TI  - [Cell cycle arrest at M phase induced by vinblastine in MOLT-4 cells].
AB  - This study was purposed to investigate the biological effect of vinblastine
      (VLS), usually known as inductor of mitotic arrest, on MOLT-4 of ALL cells and to
      evaluate its significance. The cell arrest in M phase and/or cell apoptosis were
      induced by treatment of MOLT-4 cells with 0.05 microg/ml VLS for 0 - 12 hours;
      the DNA histogram was detected by flow cytometry; the morphological changes of
      cells were observed by confocal microscopy; the cell cycle distribution, cell
      apoptosis and morphological changes of cells before and after arrest were
      analyzed by using arrest increasing rate (AIR), arrest efficiency (AE), apoptosis
      rate (AR) and morphologic parameters respectively. The results indicated that the
      cell arrest did not accompanied by significant increase of apoptosis rate; the
      DNA histogram of cell arrest showed dynamic change of cell cycle in time
      dependent manner; the arrest efficiency could be quantified. The cell arrest at M
      phase was accompanied by cell stack in S phase, the cell proliferation rate
      dropped after cell arrest occurred. The cells arrested at M phase possessed of
      characteristic morphologic features in cell mitosis. It is concluded that the
      vinblastine can solely induce arrest of MOLT-4 cells at M phase. This study
      provides experimental basis for further investigating the relation of cell cycle
      arrest to apoptosis, mechanism of checkpoint and development of new anticancer
      drugs.

PMID- 19379567
TI  - [Reversed effect of valproic acid on transcription inhibition of AML1-ETO fusion
      protein of kasumi-1 leukemic cell line].
AB  - This study was aimed to investigate the mechanism of histone deacetylase (HDAC)
      inhibitor, valproic acid (VPA), reversing transcription inhibition of AML1-ETO
      fusion protein in Kasumi-1 cell line. The mRNA expressions of AML1-ETO, AML1 and
      cyclin D2 were detected by semi-quantitation RT-PCR after treating kasumi-1 cells
      with VPA at different doses/and different time points. The results indicated that
      the mRNA expression of AML1-ETO showed no obvious change, when kasumi-1 cells
      were treated with VPA. Compared with control group, the expression level of AML1
      mRNA significantly increased in a dose-dependent manner. Compared with control
      group, the expression level of cyclin D2 mRNA significantly decreased when kasumi
      1 cells had been treated with 3 mmol/L VPA as well as kasumi-1 cells were treated
      with different concentrations of VPA for 3 days. In conclusion, VPA could remove
      transcription inhibition of AML1-ETO fusion protein, increase transcription of
      AML1 and down-regulate mRNA expression of AML1 target gene cyclin D2 through HDAC
      inhibiting activity.

PMID- 19379568
TI  - [Detection of bcl-2/IgH fusion gene in lymphoma by real-time polymerase chain
      reaction and its clinical significance].
AB  - The aim of this study was to investigate the bcl-2/IgH expression levels in
      patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)
      and its clinical significance. The bcl-2/IgH expression levels in bone marrow
      (BM) and/or peripheral blood (PB) of 20 patients were detected by using SYBR
      Green I real-time polymerase chain reaction, and the dynamic monitoring for bcl
      2/IgH expression level in 4 of these patients was performed. The results showed
      that in patients with bcl-2/IgH-positive there was no statistically significant
      difference in the relative copy-numbers of bcl-2/IgH fusion gene in BM and PB
      (4.23 and 2.73 respectively, p = 0.107), but the difference was significant
      before and after treatment (3.61 and 2.69 respectively, p = 0.000), the
      expression level of bcl-2/IgH fusion gene in newly diagnosed and relapsed group
      was remarkably higher than that in remission group (p = 0.008). The bcl-2/IgH
      expression level in PB increased evidently 3 months prior to the clinical relapse
      in one case out of dynamically monitored 4 cases. It is concluded that the bcl
      2/IgH expression level is associated with the disease status, the expression
      level is high in newly diagnosed and relapsed patients and low in those who
      achieved remission, the bcl-2/IgH fusion gene expression level decreased
      evidently after therapy, this change may be related to the clinical disease
      progression, the results suggest that peripheral blood can be regarded as the
      resource for detection of bcl-2/IgH fusion gene.

PMID- 19379569
TI  - [Inhibition effect of gambogic acid on MUTZ-1 cell line and its possible
      mechanism].
AB  - This study was aimed to investigate the effects of gambogic acid on the cells of
      high-risk patients with myelodysplastic syndrome (MDS) in vitro and its
      mechanism. The inhibition effect of gambogic acid on growth of MUTZ-1 cell line
      of MDS-RAEB was detected by MTT method. Apoptosis and cell cycle were detected by
      morphological observation and flow cytometry respectively. The expressions of
      bax/bcl-2 gene at mRNA level were detected by RT-PCR. The results indicated that
      the Gambogic acid inhibited the growth of MUTZ-1 cells, the inhibitory rate of
      gambogic acid with the range of 0.2 - 0.8 microg/ml was enhanced along with
      increasing of drug concentration. Flow cytometric assay showed that the apoptotic
      rate of MUTZ-1 cells treated by gambogic acid also was enhanced along with
      increasing of drug concentration, the apoptotic rates resulting from gambogic
      acid (0, 0.4, 0.6, 0.8 microg/ml) were (5 +/- 0.5)%, (13 +/- 0.5)%, (37 +/- 0.7)%
      and (56 +/- 0.6)% respectively. The characteristic changes of apoptosis emerged
      in MUTZ-1 cells after being exposed to gambogic acid. Gambogic acid could
      significantly down-regulate the expressions of bcl-2 gene in a dose dependent
      manner, however, it had no effects on bax gene. It is concluded that within the
      range of concentration from 0.4 to 0. 8 microg/ml, gambogic acid can inhibit the
      growth of MUTZ-1 cells by inducing their apoptosis and down-regulating the
      expression of bcl-2 gene, which may be one of the main mechanisms underlying its
      antitumor effects.

PMID- 19379570
TI  - [Expression of cyclin A1 mRNA in patients with myelodysplastic syndrome and its
      clinical significance].
AB  - The purpose of this study was to evaluate the expression of cyclin A1 mRNA in
      patients with myelodysplastic syndrome (MDS) and its clinical significance. The
      expression of cyclin A1, cdk2 and p21(cip1) mRNA in the bone marrow from 56
      patients with MDS and 10 normal control were measured by using reverse
      transcription polymerase chain reaction (RT-PCR) technique. The results indicated
      that the positive rate and the expression level of cyclin A1 in MDS patients
      (69.64%; 0.964 +/- 1.879) were significantly higher than those in normal control
      (0%; 0.012 +/- 0.014) (p < 0.01). Among de-novo MDS patients, the expression
      level of cyclin A1 mRNA in the MDS-RAEB group (1.895 +/- 1.769) was higher than
      that in MDS-RA group (0.629 +/- 1.583) (p < 0.01). The expression level of cyclin
      A1 mRNA in post-treatment group was significantly lower than that in prior
      treatment group (p < 0.01). It is concluded that the mRNA expression of cyclin A1
      in MDS patients is higher than that in normal control, the abnormal expression of
      cyclin A1 may be used as a prognostic marker in MDS patients.

PMID- 19379571
TI  - [Expression of vascular cell adhesion molecule-1 in patients with multiple
      myeloma and its significance].
AB  - In order to investigate the expression of vascular cell adhesion molecule-1 (VCAM
      1) in patients with multiple myeloma and its significance, the expression of VCAM
      1 in 23 patients were detected by reverse transcription-PCR (RT-PCR) and then
      compared with that in normal control. The results showed that the expression of
      VCAM-1 in patients with newly diagnosed and relapsed/refractory multiple myeloma
      was much higher than that in normal control and in patients reached plateau stage
      (p < 0.05). There was no statistically significant difference between newly
      diagnosed and relapsed/refractory patients (p > 0.05). It is concluded that the
      expression of VCAM-1 in patients with multiple myeloma is abnormal, which may be
      an important factor for the pathogenesis of multiple myeloma.

PMID- 19379572
TI  - [Effect of rapamycin on proliferation, apoptosis and regulation of chemokine
      receptor CXCR4 in RPMI8226 cells].
AB  - This study was purposed to investigate the effect of rapamycin on proliferation,
      apoptosis, cell cycle progression and the regulation of chemokine receptor CXCR4
      on RPMI8226 cells. Different concentrations of rapamycin were used to treat the
      multiple myeloma cell line RPMI8226 for different times. The proliferation of the
      cells was detected by MTT assay; the apoptosis rate and cell cycle were
      determined by flow cytometry (FCM); apoptosis of cells was observed by inverted
      microscopy; the cylin D1, CXCR4 and mTOR mRNA expressions were detected by RT-PCR
      or FQ-PCR after treating RPMI8226 cells with different concentrations of
      rapamycin. The results indicated that the rapamycin could inhibit the
      proliferation of RPMI8226 cells and induce their apoptosis. The cell cycle was
      arrested at the G(0)/G(1) phase. PCR results showed the down-regulation of mTOR,
      cyclin D1 and mTOR mRNA expressions after treating RPMI8226 cells with different
      concentrations of rapamycin for 24 hours. It is concluded that the rapamycin
      significantly inhibits the growth of RPMI8226 cells in a dose-and time-dependent
      mannes and induce cell apoptosis. Cell cycle arrests at the G(0)/G(1) phase, may
      be due to the down-regulation of the mTOR and cyclin D1 expressions. In
      additions, the down-regulation of CXCR4 mRNA expression is correlated with the
      reduction of adhesion between myeloma cells and stromal cells.

PMID- 19379573
TI  - [Ameliorative effect of rat bone marrow mesenchymal stem cell transplantation on
      infracted heart function].
AB  - This study was purposed to investigate the effects of rat marrow mesenchymal stem
      cell (rMSC) transplantation on left ventricular (LV) function in a rat myocardial
      infarction model. Myocardial infarction was performed in male Lewis rats by
      ligating the proximal left coronary artery. Rats were randomly divided into 3
      groups: sham operation group (only thoracotomy, n = 8), AMI group (DF12
      injection, n = 10), rMSC group (Dil-Labeled rMSC transplantation). At 8 weeks
      later, the cardiac functions including left ventricular ejection fraction (LVEF),
      left ventricular end systolic pressure (LVESP), left ventricular end diastolic
      pressure (LVEDP), +dp/dtmax and -dp/dtmax were evaluated by echocardiography and
      cardiac catheterization. The presence and differentiation of engrafted cells were
      assessed. CD31 was detected by immunohistochemical staining to demonstrate
      neovascular formation. The results indicated that the cultured in vitro rMSC
      expressed CD90, CD44, CD105, CD54; did not express CD34, CD45, CD31, as compared
      with AMI group, rMSC group showed a significant increase of LVEF, LVESP,
      +dp/dtmax, -dp/dtmax and a significant decrease of LVEDP. Immunofluorescence
      demonstrated that some transplanted rMSCs were positive for myosin, suggesting
      that small number of transplanted rMSCs differentiated into cardiac-like cells.
      Immunostaining showed marked augmentation of capillary density in the rMSC group
      than that of AMI group. It is concluded that transplanted rMSCs can differentiate
      into cardiac-like cells and rMSC transplantation can improve LV function after
      myocardial infarction in rats.

PMID- 19379574
TI  - [Comparison of biological characteristics of bone marrow mesenchymal stem cells
      in acute myeloid leukemia with those from non-leukemia].
AB  - This study was aimed to compare partial biological characteristics of bone marrow
      mesenchymal stem cells (BMMSCs) in AML patients, AML patients with complete
      remission (CR) and non-leukemia patients. The bone marrow (BM) MSCs were divided
      into 3 groups: group of MSCs from AML patients, group of MSCs from AML patients
      with CR, group of MSCs from non-leukemia patients. The morphologic features of
      MSCs were observed by light microscopy; CFU-F numbers of MSCs were counted after
      Wright-Giemsa staining in situ; the fusion times of MSCs were determined; the
      growth curves of MSCs were drawn by counting cell numbers; the immunophenotypes
      and cell cycle of MSCs were detected by flow cytometry; the DI values of MSCs
      were calculated. The results showed that the morphologic features of MSCs in 3
      groups did not display difference; there was significant difference (p < 0.01) of
      CFU-F numbers in 3 groups, while CFU-F number of MSCs in AML group was minimal;
      there was significant difference of MSC fusion time in 3 groups, while fusion
      time of MSCs in AML group was most long; the growth curves of MSCs in 3 groups
      were similar; MSCs in 3 groups highly expressed CD105 and CD106, but not
      expressed CD45; the cell distribution ratios at phase of G(0)/G(1) for MSCs in 3
      groups were 89.9 +/- 4.0%, 90.2 +/- 3.0% and 91.0 +/- 3.0% respectively; the DI
      values of MSCs in 3 groups were between 0.9 and 1.1. It is concluded that no
      significant difference of biological characteristics of the second generations of
      MSCs is found between those in leukemia and non-leukemia patients.

PMID- 19379575
TI  - [Differentiation potential of EGFP gene-modified mesenchymal stem cells
      transfected by lentiviral vector].
AB  - This study was aimed to investigate the differentiation potential after EGFP gene
      modified mesenchymal stem cells (MSCs) transfected by lentiviral vector (LV).
      After isolated, cultured and identified, MSCs were transfected with the
      lentiviral vector carrying EGFP gene in vitro. The transfection efficiency was
      measured by observing the expression of green fluorescence protein. At last, the
      transfected MSCs were induced into adipocytes in adipogenesis supplement medium,
      the induction level was detected by Sudan fat stain. The results indicated that
      after transfection for 72 hours, weak fluorescence in MSCs was observed under
      fluorescence microscope. After 21 days, many lipid droplets with high
      refractivity occurred in cytoplasm of transfected MSCs, and showed orange in
      Sudan black stain. There were no significantly differences between transfected
      and non-transfected cells (p > 0.05). It is concluded that MSCs were successfully
      transfected by LV carrying EGFP gene. The transfected MSCs maintain multiple
      differentiation and proliferation potential. In the adipogenesis supplement
      medium, transfected MSCs also can be induced to differentiate into adipocytes.
      MSCs can act as target cells for gene therapy.

PMID- 19379576
TI  - [Comparison of migration characteristics of MSCs in different assay systems].
AB  - The aim of this study was to explore the difference of MSC migration mediated by
      SDF-1/CXCR4 axis through Boyden chamber in vitro migration assay. The SDF-1
      density-dependence of MSC migration was observed. Subsequently, the effects of
      different blocking agents on hSDF-MSC migration were observed after MSC were
      treated with 50 nmol/L wortmannin, 10 micromol/L LY294002, 50 micromol/L PD98059,
      10 micromol/L U73122, 126 micromol/L AMD3100 and 50 nmol/L verapamil
      respectively. The results showed the efficiency of MSC migration increased
      gradually with the increasing of hSDF-1 density. And after MSCs treatment with 50
      nmol/L wortmannin, 10 micromol/L LY294002, 50 micromol/L PD98059, 10 micromol/L
      U73122 and 126 micromol/L AMD3100 respectively, the ability of MSC migration
      decreased. The ability of MSCs migration obviously decreased when MSCs were
      treated with U73122, AMD3100. It is concluded that the SDF-1/CXCR4-mediated MSC
      migration may be related to mitogen-activated protein kinase (MAPK),
      phosphatidylinositol phospholipase C (PI-PLC) and protein kinase (PKC) signal
      pathways.

PMID- 19379577
TI  - [Effects of SDF-1/CXCR4 on the chemotaxis of cord blood AC133(+) cells].
AB  - The aim of this study was to explore the effects of the stromal cell-derived
      factor (SDF-1) and chemokine receptors (CXCR4) on chemotaxis of cord blood
      AC133(+) cells. The optimal SDF-1 concentration was determined in Transwell
      System. The cell migration was calculated from the number of cells passing
      through polycarbonate membrane with 8 microm pore. The expressions of CXCR4 in
      fresh and cultured cord blood AC133(+) cells were analyzed by flow cytometry with
      two-color direct immunofluorescence. The results showed that the chemotactic rate
      of fresh cord blood AC133(+) cells increased along with increasing concentrations
      of SDF-1, however, it tended to be stable when the concentration of SDF-1 reached
      150 ng/ml. There was no difference in the chemotactic rate of cord blood AC133(+)
      cells between the group with SDF-1 adding CXCR4-blocking antibody and the group
      without SDF-1. When AC133(+) cells were cultured in vitro with hemopoietic growth
      factors, the expression of CXCR4 increased at the early stage, but decreased
      gradually along with time extending. In conclusion, there was correlation between
      the chemotactic rate of AC133(+) cells and the expression of chemokine receptor
      CXCR4.

PMID- 19379578
TI  - [Contribution of SDF-1/CXCR4 axis on proliferation of megakaryocyte co-cultured
      with human umbilical cord blood-derived stromal cells].
AB  - In order to investigate the effect of stromal cell derived factor-1 (SDF-1)/CXCR4
      on the proliferation of megakaryocytic line-HEL cells co-cultured with human
      umbilical cord blood-derived stromal cells (hUCBSCs) and to further elucidate the
      mechanism of SDF-1/CXCR4-mediated functions, the HEL cells were co-cultured with
      hUCBSCs or human bone marrow stromal cells (hBMSCs), the suspended HEL was used
      as control. The concentrations of SDF-1 in supernatant of hUCBSCs and hBMSCs were
      detected by ELISA assay. The expression of CXCR4 membrane-bound protein of HEL
      cells was detected by laser confocal scanning microscopy and flow cytometry, and
      the expression of CXCR4 mRNA was detected by RT-PCR. The result showed that the
      concentrations of SDF-1 in different groups were the same at the early stage of
      culturing. But at 6 days after seeding, the concentrations of SDF-1 increased
      significantly in the hUCBSCs group, even though the passage was done. By means of
      laser confocal microscopy, the expression of CXCR4 protein and also red dots of
      fluorescence could be detected in cytoplasm of HEL cells co-cultured with
      hUCBSCs. However, there was no significant differences of the CXCR4 mRNA level
      between different groups (p > 0.05). It is concluded that hUCBSCs may play
      important roles in secreting high level of SDF-1 and regulating megakaryocyte
      expression of CXCR4.

PMID- 19379579
TI  - [Effect of doxorubicin induced GM-CSF gene expression regulated by Egr-1 promoter
      on recovery of hematopoietic function in bearing-melanoma mice].
AB  - This study was purposed to investigate the effect of hematopoietic growth factor
      expression regulated by Egr-1 promoter on the recovery of hematopoietic function
      in bearing-melanoma mice after chemotherapy with doxorubicin (ADM). The human GM
      CSF cDNA and enhanced green fluorescence protein (GFP) cDNA were linked together
      with internal ribozyme entry site (IRES) and then were inserted into the
      expression vector pCI-neo under control of the Egr-1 promoter (Egr-EG). This
      vector was transduced into human bone marrow stromal cell lines HFCL by
      lipofectamine and was transfused in severe combined immunodeficiency (SCID) mice.
      The experimental mice were randomly divided into 4 groups (6 mice in each group):
      (1) HFCL/EG + ADM group in which the HFCL/EG cells were transplanted
      intravenously in SCID mice bearing melanoma, ADM was given intraperitoneally
      after 3 days; (2) HFCL + ADM group in which the HFCL cells were transplanted
      intravenously, ADM was given intraperitoneally after 3 days; (3) HPCL/EG group in
      which HFCL/EG cells were transplanted alone; (4) HFCL group in which HFCL cells
      were transplanted alone. The dynamic change of peripheral blood picture was
      assayed by hemocytometer; the eGFP(+) human stromal cells were detected by flow
      cytometry; the expression of GM-CSF mRNA and protein were determined by RT-PCR
      and Western blot respectively. The results indicated that as compared with
      HFCL/EG and HFCL groups, the leukocyte count in HFCL/EG + ADM group decreased,
      but decrease level was weaker than that in HFCL + ADM group, meanwhile the
      recovery of leukocyte count was earlier than that in HFCL + ADM group. The CFU-GM
      amount between 4 groups showed no significant difference. The detection results
      showed that the inhibitory rate of tumor was related to chemotherapy, but not to
      expression of exogenous gene; the eGFP(+) stromal cells existed in bone marrow of
      mice treated with ADM. The RT-PCR and Western blot assays revealed enhancement of
      GM-CSF mRNA and protein. It is concluded that the ADM-inducible GM-CSF gene
      therapy regulated by Egr-1 promoter may promote the hematopoietic recovery after
      chemotherapy.

PMID- 19379580
TI  - [Influence of high mobility group box 1 on migration of human cord blood CD34(+)
      cells].
AB  - The objective of study was to explore the influence of high mobility group box 1
      (HMGB1) on migration of cord blood CD34(+) cells and their mechanism of
      migration. The expressions of receptor for advanced glycation end products
      (RAGE), toll-like receptor-2 (TLR2) and TLR4 were detected by flow cytometry. The
      CD34(+) cells in umbilical cord blood (CB) were enriched by MiniMACS and were
      exposed to various concentration of HMGB1 (10, 50, 100, 1, 000 ng/ml), then the
      migration effect of HMGB1 on umbilical cord blood (UCB) CD34(+) cell count was
      determined by microscopy, the chemotactic index was calculated. The CD34(+) cells
      untreated with HMGB1 were used as control. The results indicated that the purity
      of the isolated CD34(+) cells was more than 98%. The HMGB1 could promote the
      migration of CD34(+) cells, and the migration effect of HMGB1 on CD34(+) cells in
      certain concentrations gradually increased along with raise of concentration, the
      strongest effect was observed in concentration of 100 ng/ml, there was
      significant difference as compared with control (p < 0.01). Anti-RAGE antibody
      partially inhibited the migration effect of HMGB1 on CD34(+) cells. It is
      concluded that the HMGB1 in certain concentration can enhance migration of
      CD34(+) cells, which may be mediated through RAGE.

PMID- 19379581
TI  - [Reconstitution of NK cells and their receptors in patients with acute leukemia
      following unrelated cord blood stem cell transplantation].
AB  - This study was to investigate the reconstitution of NK cells and their receptors
      after unrelated cord blood stem cell transplantation (UCBT) and its clinical
      importance. 11 cases of acute leukemia underwent UCBT were enrolled in this
      study. The reconstitution of NK cells and their surface receptors as well as the
      the recovery of T and B cells within 90 days after clinical engraftment following
      UCBT were measured and analysed by flow cytometry. The results indicated that the
      recovery of NK cells appears to be relatively early. CD3(-)56(+) NK cell count
      was (35.12 +/- 18.66)% of peripheral blood (PB) lymphocytes on the day of
      clinical engraftment and higher than that in normal. The peak of the NK cells
      reached to (37.8 +/- 17.52)% of lymphocyte at 30 days after clinical engraftment.
      NK count was (30.4 +/- 19.14)% at 60 days after clinical engraftment when the
      absolute NK cell count reached to the peak (up to 544 cells/microl) in PB. The
      activated receptor NKG2D was reconstituted fast and high expressed [(79.58 +/-
      8.71)%] at the time of clinical engraftment with a tendency of gradual elevation,
      which reached to peak value (82.55 +/- 9.10)% at day 60. Another activated
      receptor NKp46 also reconstituted fast, and maintained at a high level even at 90
      days after clinical engraftment. The expression of NKG2A was lower than that of
      the activated receptor of NK cells, which tendency lasted for at least 90 days
      after clinical engraftment. The reconstitution of T cells in PB after UCBT was
      relatively slow with lower expression rate. It is concluded that the
      reconstitution of NK cells in patients with acute leukemia is earlier following
      UCBT. The earlier recovery of activated receptor of NK cells, especially NKG2D,
      suggests that the activation of NK cells may play a role in graft versus leukemia
      (GVL) effect in the early period after UCBT.

PMID- 19379582
TI  - [Expression and clonal proliferation of TCR Vbeta subfamilies of peripheral T
      cells in acute myeloid leukemia patients].
AB  - This study was purposed to investigate the expression and clonal proliferation of
      receptor (TCR) Vbeta subfamilies of the T-cells in acute leukemic patients at
      different disease status (onset, complete remission or relapse) and to analyze
      the influence of the leukemic cell load on anti-leukemic effect of peripheral T
      lymphocytes of the patients. Gene sequences of peripheral TCR Vbeta 24 families
      from 11 leukemic patients and 3 normal donors were expanded by RT-PCR. Genescan
      technique was applied to evaluate clonal expression of the TCRVbeta subfamilies,
      clonal characteristics of the CDR3 from peripheral blood of AML patients at
      different disease status. The application, clonal proliferation, cellular
      complexity of T-cells, and the variation of immunotypes of T-cells were compared.
      The results indicated that the lower and partial distribution of TCR Vbeta
      subfamily was found in all 11 patients when firstly diagnosed; the expression of
      TCR Vbeta subfamilies after induction in vitro increased; obvious elevation of
      TCR Vbeta subfamilies was observed in patients at complete remission although
      expression level was still lower than normal, whereas the significant descent of
      TCR Vbeta subfamilies was detected in 4 relapsed patients. Only 1 - 2 clonal
      proliferation of TCR Vbeta subfamilies existed in 9 out of 11 patients at initial
      diagnosis which increased at remission. The status of clonal proliferation of
      Vbeta subfamily T-cells continued regardless of any different disease status in
      most patients. There was an obvious decrease of CDR3 complexity at initial
      diagnosis or relapse, while CDR3 complexity would be partially improved at
      remission. It is concluded that the restrict distribution and expression of TCR
      Vbeta subfamilies were found in AML patients. Clonal proliferation of T-cells
      Vbeta subfamily continuously exists regardless of any different disease status in
      most patients. Some Vbeta subfamilies sustain clonal proliferation at different
      disease status. Some clonal proliferations of Vbeta subfamilies are associated
      with the effects of leukemic cells, CDR3 complexity obviously decreases under
      disease status which can be partially improved at remission.

PMID- 19379583
TI  - [In vitro investigation on specific anti-leukemia cell effect of CTL induced by
      sensitized dendritic cells from umbilical cord blood].
AB  - This study was aimed to investigate the specific anti-leukemia cell effect of
      cytotoxic T lymphocytes (CTLs) induced by HL-60 or K562 cell-sensitized dendritic
      cells (DCs) from umbilical cord blood. 12 units of human umbilical cord blood
      (UCB) were collected and the mononuclear cells (MNCs) were isolated from UCB,
      then cultured with granulocyte monocyte colony- stimulating factor (GM-CSF),
      interleukin 3 (IL-3), recombinant human stem cell factor (SCF) and EPO for 3 - 4
      weeks. Flow cytometry was used to determine the number of DCs and cell surface
      antigens before and after culture with monoclonal antibodies including CD83,
      CD1a, CD11c and CDw123. HL-60 and K562 were frozen-thawed, and released their
      tumor antigen peptides (TAP). The CTLs were produced by sensitizing T lymphocytes
      with DC-loaded HL-60 and K562 cell antigens. The test of (3)H-TdR incorporation
      was used to detect the immunostimulation activity of DCs. MTT assay was applied
      to evaluate specific cytotoxicity of CTL on leukaemia cells. The results
      indicated that the MNCs of UCBs cultured with GM-CSF, IL-3, EPO and SCF were
      shown to differentiate into CD1a(+) CD11c(+) CD83(+) CDw123(+) DCs. Numbers of
      DCs from UCBs remarkably increased in 2 - 4 weeks and then decreased. After
      culture with cytokines DCs increased (10.6 - 28.2) x 10(5)/ml in actual numbers.
      The CTL induced by DC pulsed with HL-60, K562 frozen-thawed lysates were
      effective to kill HL-60 and K562. Cytotoxicity of CTL to HL60 and K562 were
      (42.04 +/- 8.46)% and (31.25 +/- 11.07)% respectively. It is concluded that the
      MNCs of UCBs cultured with cytokines of GM-CSF, SCF, EPO and IL-3 can
      differentiate into CD1a(+), CD83(+), CD11c(+) and CDw123(+) DCs. The CTL induced
      by DCs pulsed with HL-60, K562 frozen-thawed lysates can effectively kill HL-60
      and K562. These DCs as antigen presenting cells play an important role in cancer
      immunotherapy.

PMID- 19379584
TI  - [Analysis of immunophenotypes of acute lymphoblastic leukemia by three color flow
      cytometry].
AB  - This study was purposed to investigate the immunophenotype characteristics and
      their significance in subtypes of acute lymphoblastic leukemia (ALL). The
      immunophenotypes in 40 cases of ALL were analyzed with three color flow cytometry
      using CD45/SSC two-parametric gating. The results showed that the three color
      flow cytometry assay using CD45/SSC two-parametric gating could accurately
      distinguish each other from lymphocytes, monocytes, granulocytes, erythroblasts
      and primitive cells in bone marrow and/or peripheral blood. Among 40 cases of
      ALL, B-ALL was 26 cases, T-ALL was 11 cases, HAL was 3 cases. All of the 26 cases
      of B-ALL expressed CD19 with positive rate of 100%, meanwhile 11 cases of T-ALL
      most highly expressed CD17 with positive rate of 100%. 12 cases of ALL with
      myeloid antigen expression (My-ALL) were involved in ALL, the incidence of these
      cases was almost 30% (12/40). The CD13 was expressed most highly in myeloid
      antigens. All 3 cases of HAL coexpressed myeloid and B-lineage antigens, among
      them CD34 was expressed in 2 cases with positive rate of 66.67%. It is concluded
      that three color flow cytometry assay using CD45/SSC two-parametric gating can
      exclude the interference of normal cells, thereby the results are more reliable
      and more accurate.

PMID- 19379585
TI  - [Expression and function of Ahi-1 gene in Jurkat cells].
AB  - This study was aimed to investigate the expression, protein localization and
      function of Ahi-1 gene and its encoding protein in Jurkat cells. The expression
      of Ahi-1 mRNA and protein were measured by Northern and Western blot
      respectively. The plasmid containing prototype Ahi-1 was constructed and
      transfected into Jurkat cells. The Jurkat-A and Jurkat-C cells which either over
      expressed the prototype Ahi-1 or not were obtained by selection with G418. The
      proliferation of the cells was assayed by XTT. The colony formation potential of
      the leukemia cells was checked by semisolid agarose culture. The results showed
      that three different transcripts of Ahi-1 (6.5,4.2 and 2 kb) were expressed in
      peripheral blood lymphocytes (PBLs), Jurkat and HUT78 cells. Ahi-1 protein with
      140 kD localized in the cytoplasm majorly while traceless in the nucleus of
      Jurkat cells and PBLs from normal donor. Ahi-1 protein with 120 kD could be
      detected in the nucleus fraction of PBLs. Very low level of Ahi-1 protein with
      120 kD was expressed in Jurkat cells. Up-regulating expression of Ahi-1 protein
      with 140 kD in the nucleus was found in Jurkat cells after exposure to
      meisoindigo, cytarabine, homoharringtonine, methotrexate and etoposide, down
      regulating expression of Ahi-1 with 140 kD in the cytoplasm was observed after
      treatment with meisoindigo. The growth and colony formation potential were
      inhibited in the Jurkat-A cells, as compared to Jurkat-C cells. Total c-myb and
      phosphorylated AKT protein were continuously expressed in the Jurkat-C and Jurkat
      A cells at similar level, but more phosphorylated c-myb was observed in Jurkat-A
      cells. It is concluded that three different transcripts of Ahi-1 at 6.5, 4.2 and
      2 kb are detected in Jurkat cells; the Ahi-1 protein with 140 kD majorly
      expresses in the cytoplasm fraction and exposure to multiple chemotherapeutic
      compounds increased its expression in nucleus fraction. Over-expression of
      exogenous Ahi-1 can not only inhibit the growth and colony formation potential of
      Jurkat cells, but also induce the phosphorylation of c-myb in Jurkat cells.

PMID- 19379586
TI  - [Construction, identification of human B7.1 eukaryotic expressing vector and its
      expression on leukemic cells].
AB  - The aim of study was to investigate the construction, identification and
      expression of human B7.1 (CD80) eukaryotic expressing vector on HL-60 cells. B7.1
      gene was subcloned from the cloning vector using PCR. The PCR products and
      eukaryotic expressing vector (pHook) both were separately digested with ApaI,
      SalI and were ligated using T4 DNA ligase. The ligases products were transduced
      into DH-5alpha. B7.1 gene containing clones was selected by digestion with ApaI
      and SalI, and were further confirmed by sequencing of DNA. HL-60 cells were
      transfected with B7.1 by using lipofectamine and detected by immunofluorescence,
      SABC and FACS methods. The results showed that the size of PCR products was about
      620 bp. Five clones were ampicillin-resistant and all could be digested by ApaI
      and SalI to produce 620 bp gene fragment that had the same size of B7.1, which
      means that the B7.1 recombinant vector has been constructed successfully. Further
      sequencing confirmed the validity of the construction. No nucleotide mutation was
      found, B7.1 effectively expressed on HL-60 cells with 70%, 65% and 92.7% by
      immunofluorescence, SABC and FACS respectively. It is concluded that the human
      B7.1 (CD80) eukaryotic expressing vector can be successfully constructed by
      molecular cloned methods and can stably effectively express on the membrane of
      B7.1-negative acute myelocytic leukemia (AML) cell line HL-60. It is inferred
      that the vaccine prepared by using this method may have immunotherapeutic and
      immuno-protective effects.

PMID- 19379587
TI  - [Investigation on MS-PCR as a method for detecting minimal residual disease in
      acute leukemia].
AB  - The aim of this study was to investigate the feasibility of monitoring minimal
      residual disease (MRD) of leukemia with methylation specified-polymerase chain
      reaction (MS-PCR). The HL-60 cells with Id4 gene complete methylation and Hek937
      cells with Id4 gene complete unmethylation were mixed in accordance with
      different ratios of cells and were divided into 3 groups: group A (10% HL-60 +
      90% Hek937), group B (1% HL-60 + 99% Hek937) and group C (0.1% HL-60 + 99.9%
      Hek937). The MS-PCR technique was used to detect the methylation status of Id4
      gene in different ratios of leukemia cells. The results indicated that the
      methylation specific amplification of Id4 gene with 155 bp was observed in HL-60
      cells showing complete methylation of Id4 gene; while the unmethylation specific
      amplication of Id4 gene with 156 bp was found in Hek937 cells, showing complete
      unmethylation. The methylation specific amplification of Id4 gene with 155 bp and
      unmethylation specific amplification of Id4 gene with 156 bp were simultaneously
      detected in A, B and C groups, which showed the expression of Id4 gene
      methylation. In conclusion, the MS-PCR technique can detect the Id4 gene
      methylation in leukemia cell sample containing 0.1% of HL-60 cells, moreover the
      Id4 gene methylation in various leukemia cells shows no significant difference,
      thereby use of MS-PCR to detect the Id4 methylation level may be a potential
      approach for monitoring of MRD. Id4 gene promoter methylation is a candidate of
      biomarker for MRD detection in acute leukemias.

PMID- 19379588
TI  - [Efficacy of induction chemotherapy for patients with high-risk myelodysplastic
      syndrome (MDS) or MDS-transformed acute myeloid leukemia with CHG regimen and its
      comparison with regimen GAG and HA].
AB  - This study was aimed to investigate the efficacy of moderate intensity regimen,
      CHG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor (G
      CSF)) on the patients with high-risk MDS or MDS-transformed acute myeloid
      leukemia. 30 newly diagnosed adult patients with high-risk MDS or MDS-transformed
      AML were enrolled in this clinical trial to evaluate the efficacy of sequential
      low-dose homoharringtonine/cytarabine chemotherapy combined with G-CSF priming.
      Homoharringtonine and Ara-C were injected intravenously at doses of 1 mg and 25
      mg daily for 14 consecutive days respectively, G-CSF was injected subcutaneously
      once daily at a dose of 300 microg on 12 hours prior to chemotherapy and
      continued given until the end of chemotherapy or when the peripheral WBC count
      reached > 20 x 10(9)/L. This regimen was given only for one course, and followed
      by conventional chemotherapy as maintenance or consolidation therapy when CR
      achieved. 33 patients with high- risk MDS and MDS-transformed AML were injected
      aclarubicin/Ara-C intravenously at doses of 10 mg and 25 mg for 8 and 14
      consecutive days respectively, G-CSF was used at the same dose and the same way
      as the CHG regimen. 33 patients with high-risk MDS and MDS-transformed AML were
      treated with HHT/Ara-C intravenously at doses of 2 - 3 mg and 100 - 150 mg daily
      for 7 consecutive days respectively, G-CSF was injected when WBC count was below
      4 x 10(9)/L, and it was stopped to be used when WBC count was > 4 x 10(9)/L. The
      results showed that (1) 14 patients achieved complete remission (CR) (46.67 %)
      and 7 patients achieved partial remission (PR) (23.33 %) with one course of CHG
      regimen, total effective rate was 70%; 14 patient achieved CR (42.4%) and 9
      patients achieved PR (27.3%) with one course of CAG regimen, total effective rate
      was 69.7%; 7 patient achieved CR (33.3%) and 3 patients achieved PR (9.1%) with
      one course of HA regimen, total effective rate was 42.4%. There was no
      statistical difference between the effective rate of CHG and CAG, but difference
      was significant between CHG and HA. (2) Agranulocytosis (neutrophil < 0.5 x
      10(9)/L) occurred in 12 cases (40%) of CHG-treated patients with a mean 8 days of
      agranulocytic period, so the infectious complications were less serious and
      tolerable without treatment-related death. (3) Among 14 out of 30 patients with
      CR, 9 relapsed, the mean duration from CR to replace was 8.2 months. All relapsed
      patients reusing CHG regimen did not achieved CR again. (4) Among 13 cases with
      CR, 6 patients just received HA or DA regimens as consolidatory and intensive
      chemotherapy after CR have relapsed, the mean CR time was only 6.1 months.
      Otherwise, the mean CR time of 7 CR patients received alternative succeeded
      chemotherapy containing
      mitoxantrone/idarubicin/THP/homoharringtonine/daunorubicin/aclarubicin after CR
      was 10.6 months; and among them 4 are still in continuous CR. It is concluded
      that the CHG chemotherapy regimen has a similar effect with CAG but better than
      HA, and in a saft chemotherapy regimen with slight myelosuppression in clinical
      application, strong and alternative succeeded chemotherapy is necessary for CR
      patients to keep longer CR and survival.

PMID- 19379589
TI  - [IDA-FLAG regimen in treatment of patients with refractory or relapsed acute
      leukemia].
AB  - The objective of this study was to evaluate the efficacy and toxicity of the
      fludarabine combination with high-dose cytarabine (Ara C), idarubicin and
      granulocyte colony-stimulating factor (G-CSF) (IDA-FLAG regimen) in treatment of
      refractory/relapsed acute leukemia (AL) patients. 4 patients were male aged from
      32 to 44 years, consisted of 3 cases of acute myeloid leukaemia (AML) and 1 cases
      of acute lymphocytic leukaemia (ALL). All the patients were treated with
      idarubicin (10 - 12 mg/m(2)/d, days 1 to 3), fludarabine (50 mg/d, days 1 to 5),
      cytarabine (2 g/m(2)/d, days 1 to 5) and granulocyte colony-stimulating factor (G
      CSF, 300 microg/d, days 0 to 5). The results showed that after one course of
      induction therapy, 4 patients all achieved complete remission (CR), in which 2
      patients were in continuous CR after a follow-up of 3 and 4 months; 1 patient
      relapsed after 10 months and another one patient died of thrombotic
      thrombocytopenic purpura at 4 months after allogeneic peripheral blood stem cell
      transplantation. Myelosuppression and infections due to neutropenia were the most
      frequent adverse effects, severe nonhematologic toxicity and the early death were
      not observed in these patients. In conclusion, the IDA-FLAG regimen is effective
      in treatment of patients with refractory and relapsed AL, the adverse effects
      from this regimen were well tolerated by patients, which gains time for further
      treatment.

PMID- 19379590
TI  - [Clinical significance of flow cytometry in diagnosis of immunorelated
      pancytopenia].
AB  - This study was purposed to explore the diagnostic role of flow cytometry in
      immunorelated pancytopenia (IRP). After 50 IRP patients were hospitalized, the
      concentration of serum ferritin, folic acid and vitamin B(12), immunologic test,
      platelet antibody, test of hepatitis A, B and C, haemolysis test and bone marrow
      smear examination were carried out, meanwhile the chromosome karyotype analysis
      and some routine examinations were performed. The 50 patients were divided into
      group A and group B. Group A consisted of 22 patients who were undefinedly
      diagnosed and intended to diagnosed as IRP, group B consisted of 28 definedly
      diagnosed patients with hematologic malignancies, including 7 cases of aplastic
      anemia, 2 of paroxysmal nocturnal hemoglobinuria, 10 of myelodysplastic syndrome,
      9 of megaloblastic anemia. In addition, 30 normal people were used as normal
      control group (group C). For groups A and B, the binding autoantibodies of bone
      marrow stem/progenitor cells, erythroblasts and myelocytes were detected by flow
      cytometry, meantime the ratio of total B-(CD10(+)) and CD5(+) B-lymphocytes in
      peripheral blood was assayed. For control group, the ratios of CD19(+) and CD5(+)
      B lymphocytes in peripheral blood were determined alone. The results indicated
      that the detection of bone marrow autoantibodies in 20 patients of group A showed
      positive with 90.90%. The IgG type was found mostly in antibody binding types,
      next the IgM type, the IgA type was fewer. The detection of bone marrow
      autoantibodies of 2 patients in group B showed positive with 7.14%. The positive
      rate in group A was obviously higher than that in group B (p < 0.01). The ratios
      of CD19(+) and CD5(+) B lymphocyte in peripheral blood were significant higher in
      group A than that in group B and control group (p < 0.01), but there was no
      significant difference between groups B and control. It is concluded that the
      application of flow cytometry in detecting the autoantibodies of bone marrow
      cells and CD19(+) B-and CD5(+) B-lymphocyte in peripheral blood can provide
      reliable diagnostic evidence and detection measure for diagnosis and differential
      diagnosis of IRP, as well as may contribute to draw up more effective therapeutic
      strategy.

PMID- 19379591
TI  - [Acute pancreatitis induced by cyclosporine a following allogeneic hematopoietic
      stem cell transplant].
AB  - Pancreatitis has not been reported in allogeneic stem cell transplant (allo-SCT)
      recipients with cyclosporine in China. This article presented a case of acute
      pancreatitis in a 49-year-old patient with AML-M2a who received allogeneic stem
      cell transplant from her HLA identical sister. The preparative regimen consisted
      of busulfan and cyclophosphamide. The cyclosporine A, short-term methotrexate and
      antilymphocyte globulin (ATG), were used to prevent the graft-versus-host disease
      (GVHD). Clinical and laboratory signs of acute pancreatitis were found in the
      patient on day 20 post-transplant. A diagnosis of acute pancreatitis was made
      although the pancreas was apparently normal at abdominal contrast-enhanced
      tomography and ultrasonography. She recovered with supportive care and reduction
      of cyclosporine dose. In conclusion, cyclosporine is the probable cause of
      pancreatitis in this patient.

PMID- 19379592
TI  - [Detection of factor IX gene mutation in patients with hemophilia B by DNA
      sequencing].
AB  - In order to investigate the patterns of FIX gene mutation in 3 unrelated
      hemophilia B (HB) patients, the activated partial thromboplastin time (APTT) and
      FIX activity (FIX: C) tests were adopted for phenotype diagnosis. All of the
      eight exons and their flank of FIX gene were amplified by polymerase chain
      reaction (PCR), the nucleic acid sequences were detected by dideoxymediated chain
      termination method. The results indicated that as compared with normal control,
      the APTT value significantly increased, FIX: C value obviously decreased, PT
      value was normal. Sequencing results showed that all of 3 HB patients had the
      changes of gene sequences, among 3 patients the G22119A point mutation of exon 6
      existed in case No.1, the G7932C point mutation of exon 2 was detected in case
      No.2 and the T32685C point mutation of exon 8 was found in case No.3. In
      conclusion, the relevant changes of gene sequences in all of 3 HB patients were
      detected, which provides some evidences for molecular mechanism of gene
      deficiency in HB patients.

PMID- 19379593
TI  - [Effects of TNF-alpha on MCP-1 and IL-8 mRNA expression in human umbilical vein
      endothelial cells].
AB  - This study was aimed to explore monocyte chemotactic protein 1 (MCP-1) and
      interleukin 8 (IL-8) expressions in human umbilical vein endothelial cells
      (HUVECs) affected by TNF-alpha and its molecular mechanism. RT-PCR assay was used
      to detect the expression of MCP-1 and IL-8 mRNA in HUVECs at various times
      following stimulation with TNF-alpha; the nuclear factor-kappa B (NF-kappaB)
      activation in HUVECs were detected by immunofluorescence. The results showed that
      after stimulation with NF-kappaB, the expression levels of MCP-1 and IL-8 mRNA in
      HUVECs increased, and changed along with different time; the expression of IL-8
      mRNA reached to peak level at 8 hours and the expression of MCP-1 mRNA reached to
      peak level at 12 hours; the expression of NF-kappaB p65 protein began increasing
      at 30 minutes and reached to peak level at 1 hour; then the staining of cytoplasm
      gradually weakened, while staining of nuclei was enhanced, which indicated
      significant nuclear translocation of NF-kappaB p65. It is concluded that the TNF
      alpha induces expressions of IL-8 mRNA, MCP-1 mRNA and NF-kappaB in HUVECs, and
      NF-kappaB activities signal pathway may play a role in IL-8 mRNA and MCP-1 mRNA
      expressions.

PMID- 19379594
TI  - [Expression of co-stimulatory molecules in peripheral blood of patients with
      idiopathic thrombocytopenic purpura in relation with platelet antibodies].
AB  - This study was aimed to detect the expression of co-stimulatory molecules CD80,
      CD86 and CD137 in peripheral blood of patients with idiopathic thrombocytopenic
      purpura (ITP), the content of platelet antibodies in serum (PAIgG), and to
      analyze the relationship between them and their correlation with the number of
      platelet in peripheral blood, so as to clarify the roles of co-stimulatory
      molecules in pathogenesis of idiopathic thrombocytopenic purpura and evaluation
      of disease status. The co-stimulatory molecules CD80, CD86 and CD137 in
      peripheral blood mononuclear cells (PBMNCs) of 48 ITP patients and 40 normal
      persons were detected by immunofluorescence and flow cytometry (FACS), PAIgG
      content in serum was detected by enzyme-linked immunosorbent assay (ELISA). The
      results showed that CD80, CD86 and CD137 expression levels in ITP patients were
      (4.92 +/- 2.02)%, (8.68 +/- 4.25)%, (5.32 +/- 2.67)% respectively, PAIgG content
      was 210 +/- 3.02 ng/10(7) PA, all these of which were significantly higher than
      these in normal control group (2.01 +/- 0.75)%, (4.56 +/- 2.06)%, (1.37 +/-
      1.25)%, PAIgG 20 +/- 1.13 ng/10(7) PA (p < 0.01). Correlation of co-stimulatory
      molecule expression with PAIgG content were positive (r = 0.302, p < 0.05), but
      correlation of co-stimulatory molecule expression with platelet number was
      negative (r = -0.369, p < 0.05). It is concluded that the co-stimulatory
      molecules CD80, CD86 and CD137 are involved in immune response and the incidence
      of ITP. Their over-expression closely associates with the pathogenesis of ITP and
      clinical status, so that correcting the abnormal expression and regulating the
      immune status may be one therapeutic strategy and have important clinical
      significance.

PMID- 19379595
TI  - [Application value of allele frequencies in direct identification of ambiguous
      HLA genotypes].
AB  - This study was aimed to investigate the application value of allele frequencies
      in direct identification of the ambiguous HLA genotypes. The HLA-A, HLA-B and
      HLADRB1 loci in 658 Chinese Han donor were detected by PCR-SBT method, the
      ambiguous genotyping samples were identified by using high resolution PCR-SSP and
      heterozygous ambiguity resolution primers (HAPRs) methods. The relative
      probability of true genotypes was calculated by using allele frequencies and was
      compared with true results. The results indicated that the relative probability
      of true genotype > 95% in 220 HLA-A ambiguous samples, 238 HLA-B ambiguous
      samples and 107 HLA-DRB1 ambiguous samples were 99.5% (221/222), 95.8% (228/238)
      and 97.7% (104/107) respectively. As compared with phenotyping results detected
      by PCR-SSP and HARP methods, the matching ratios for HLA-A, HLA-B and HLA-DRB1
      loci were 100% (222/222), 99.6% (237/238) and 99.1% (106/107) respectively, while
      the mismatch genotypes were observed only in B*3501/5501 and DRB1*1241/1504, the
      relative probability of them were 40.3% and 2.1% respectively. It is concluded
      that the detection method using allele frequencies to directly identify the
      ambiguous HLA genotypes in large scale PCR-SBT genotyping of donors not only can
      give higher accurate and reliable results, but also is a simple, rapid and cost
      saving method. This method has to be used with great care in the identify-test of
      patient-donor pair before the transplantation.

PMID- 19379596
TI  - [Identification of a novel HLA allele DRB1*1462 by sequence-based typing].
AB  - This study was to identify a novel HLA-DRB1 allele in Chinese population by
      nucleotide sequence ana- lysis. The HLA typing of genes was performed by PCR-SSO
      and PCR-SSP, the ambiguous novel allele was identified by DNA sequence analysis.
      The results showed that the sequence of this new allele differed from DRB1*140101
      by one nucleotide substitution at position 256 in exon 2 (G- > A), resulting in
      an amino acid change from Ala to Thr at codon 57. In conclusion, this allele is a
      novel one, which has been officially given the name DRB1*1462 by the WHO
      nomenclature committee in January 2006.

PMID- 19379597
TI  - [Application of SNP-arrays in hematological malignancies - review].
AB  - Single Nucleotide Polymorphism (SNP) is a DNA sequence variation caused by the
      mutation at the level of genomic nucleotides. It has been reported as the third
      generation of genetic markers. The SNP-arrays, based on the principle of SNP,
      plays an important role in disease research mainly for genomic detection of
      predisposing genes. As a convenient, confident, sensitive and efficient
      technique, SNP arrays could be applicable for the multiple-point interaction
      analysis of candidate genes, making it a promising and powerful method for DNA
      analysis. Hematological malignancies consist of various categories and their
      incidence is rising significantly. A multiple-point gene interaction has been
      reported as the essential pathogenetic mechanism of these diseases. This review
      illustrates the process of SNP-arrays in genome-wide assay and the application of
      this technique to the pathogenesis, clinical manifestation, therapeutic response
      and the prognosis of the hematological malignancies, including leukemia,
      malignant lymphoma, juvenile myelo-monocytic leukemia, myelodysplastic syndrome,
      multiple myeloma and so on.

PMID- 19379598
TI  - [New member miRNA in p53 gene signal pathway - review].
AB  - Mutations in p53 signal pathway are found in nearly all types of cancers,
      indicating its close relationship with human malignant tumors. Wide type p53 is a
      potent tumor suppressor, whose biological effects are largely due to its function
      as a transcriptional regulator. MicroRNAs (miRNAs) is an important class of
      noncoding regulatory RNA molecules, with profound impact on a wide array of
      biological processes, regulating both messenger RNA (mRNA) translation and decay
      by the combination of target mRNA. The latest studies found that miRNAs are
      important molecules during the modulation of protein expression by activation of
      p53. The miRNA biosynthesis, function and the research progress in p53 gene
      signal pathway are reviewed.

PMID- 19379599
TI  - [Advance of study on MN1 gene in acute myeloid leukemia - review].
AB  - The transcriptional coactivator MN1 has been identified as a gene overexpressed
      in certain types of human acute myeloid leukemia. Overexpression of this gene is
      associated with all inv (16) AML, retinoic acid-resistance, a worse prognosis as
      well as a shorter survival in AML patients with a normal karyotype. This article
      reviews the role of MN1 in acute myeloid leukemia including MN1 gene structure
      and action mechanism, MN1-TEL and AML with normal karyotype, MN1 and inv (16)
      AML, MN1 and retinoic ocid-resistance, and so on.

PMID- 19379600
TI  - [Progress of study on relationship between Mcl-1 gene and hematologic
      malignancies - review].
AB  - Mcl-1 (myeloid cell leukemia-1) is a member of Bcl-2 (B cell leukemia-2) family,
      which may play an important role in cell apoptosis regulation, occurrence and
      development of tumors. This paper reviews advance of studies on the function of
      the mcl-1 gene and MCL-1 protein, the signal transduction pathways (JAK/STAT,
      MAPK, PI-3K) regulating the expression of mcl-1 gene, and the relationship
      between mcl-1 gene and hematologic malignancies.

PMID- 19379601
TI  - [Advance of research on relationship between ABCG2 and drug resistance in
      hematologic malignancies - review].
AB  - ABCG2, a half-transporter concerning with the endo and exon-toxin-efflux, plays
      an important role in protecting the normal tissues from the toxin-hurt as well as
      mediating the multidrug resistance, because many of the chemotherapeutic drugs
      are the substrate of ABCG2. In this paper, the advance of research about this
      gene's single nucleotide polymorphisms (SNPs) was explained concisely. The
      relationship among ABCG2, the stem cells and the tyrosine kinase inhibitor (TKI)
      was reviewed. The research about drug resistance related-progress in hematologic
      malignancies was analyzed retrospectively and the present problems and the
      perspective in the future were discussed.

PMID- 19379602
TI  - [Mechanism of donor T cell migration and homing in the pathophysiology of acute
      graft-versus-host disease - review].
AB  - Migration of donor T cells to the host second lymphoid organs and homing of
      activated donor T cells into the target tissues play crucial role in the
      pathophysiology of acute graft-versus-host disease (aGVHD). More deep
      understanding of the mechanisms for donor T cell migration and homing reveals an
      important significance in preventing the initiation of aGVHD. In this review, the
      migration of donor T cells to host second lymphoid organs, homing of donor
      activated T cells into the target organs, homing of regulating T cells into
      target organs, the mechanisms of T cell migration and homing in process of aGVHD
      and its study prospects were summarised.

PMID- 19379603
TI  - The Journal gets a facelift and a new name.

PMID- 19379604
TI  - Deleterious effect of smoking and nasal septal deviation on mucociliary clearance
      and improvement after septoplasty.
AB  - OBJECTIVES: To investigate the effect of septal deviation, septoplasty, and
      smoking upon nasal mucociliary clearance by using saccharine test. METHODS:
      Included in this study were 40 patients (15 women and 25 men) who had septal
      deviation and septoplasty surgery performed between March and June 2006. Patients
      are classified into three groups: group I (n = 20) nonsmoking patients who had
      septoplasty surgery, group II (n = 20) smoking patients who had septoplasty
      surgery, and the control (n = 20) group. None of the control group has nasal
      breathing problem or smoking history. For determining preoperative and
      postoperative nasal mucociliary clearance (MCC) time, a saccharine test was
      performed on the patients 1 day before surgery and at the third month of
      postoperative control. RESULTS: Preoperative and postoperative nasal MCC time in
      patients of group I are statistically significantly lower than the group II (p <
      0.01). Postoperative MCC time in group I and II is significantly decreased
      compared with preoperative MCC time, statistically (p < 0.01). Preoperative and
      postoperative MCC time of group I and group II is significantly higher than MCC
      time of the control group (p < 0.01). CONCLUSION: Nasal septal deviation and
      smoking deteriorates nasal MCC time and this result can be shown easily with the
      saccharine test. Properly performed septoplasty surgery decreases nasal MCC time
      during the late postoperative period but MCC times are still longer than normal.
      The saccharine test can be used for following up the effect of septoplasty upon
      nasal mucosa.

PMID- 19379605
TI  - Chitin stimulates expression of acidic mammalian chitinase and eotaxin-3 by human
      sinonasal epithelial cells in vitro.
AB  - BACKGROUND: Sinonasal epithelial cells participate in host defense by initiating
      innate immune mechanisms against potential pathogens. Antimicrobial innate
      mechanisms have been shown to involve Th1-like inflammatory responses. Although
      epithelial cells can also be induced by Th2 cytokines to express proeosinophilic
      mediators, no environmental agents have been identified that promote this effect.
      METHODS: Human sinonasal epithelial cells from patients with chronic
      rhinosinusitis with nasal polyps (CRSwNPs) and controls were harvested and grown
      in primary culture. Cell cultures were exposed to a range of concentrations of
      chitin for 24 hours, and mRNA for acidic mammalian chitinase (AMCase), eotaxin-3,
      and thymic stromal-derived lymphopoietin (TSLP) were assessed. Other cultures
      were exposed to interleukin 4 (IL- 4) alone and in combination with dust-mite
      antigen (DMA) for 36 hours. Extracted mRNA and cell culture supernatant were
      analyzed for expression of AMCase and eotaxin-3. RESULTS: Chitin induced a dose
      dependent expression of AMCase and eotaxin-3 mRNA but not TSLP. Patients with
      recalcitrant CRSwNPs showed lower baseline expression of AMCase when compared
      with treatment-responsive CRSwNP and less induction of AMCase expression by
      chitin. DMA did not directly induce expression of AMCase or eotaxin-3. Expression
      of eotaxin-3 was stimulated by IL-4 and further enhanced with the addition of
      DMA. Levels of AMCase were not significantly affected by either IL-4 or DMA
      exposure. In some cases, the combination of IL-4 and DMA was able to induce
      AMCase expression in cell cultures not producing AMCase at baseline. CONCLUSION:
      The abundant biopolymer chitin appears to be recognized by a yet uncharacterized
      receptor on sinonasal epithelial cells. Chitin stimulates production of AMCase
      and eotaxin-3, two pro-Th2 effector proteins. This finding suggests the existence
      of a novel innate immune pathway for local defense against chitin-containing
      organisms in the sinonasal tract. Dysregulation of this function could
      precipitate or exacerbate Th2 inflammation, potentially acting as an underlying
      factor in recalcitrant CRSwNP.

PMID- 19379606
TI  - Proinflammatory impact of Staphylococcus aureus enterotoxin B on human nasal
      epithelial cells and inhibition by dexamethasone.
AB  - BACKGROUND: The pathophysiology and etiology of chronic rhinosinusitis with nasal
      polyps (CRSwNP) are poorly understood. Although a potential role of
      staphylococcal enterotoxins (SE) in the pathogenesis of CRSwNP has been detected,
      additional studies are needed on the impact of SE on nasal epithelial cells. The
      purpose of this study was to evaluate the impact of Staphylococcus aureus
      enterotoxin B (SEB) on proinflammatory cytokine/chemokine releases in primary
      human nasal epithelial cells (HNEC) of subjects with and without CRSwNP and the
      inhibitory effect of glucocorticoid on it. METHODS: Epithelial cells of NP and
      inferior turbinate (IT) were cultured serum free under stimulus of SEB, and
      interleukin (IL)-1beta, respectively. Furthermore, the inhibitory effect of
      glucocorticoid on the proinflammatory response was investigated by addition of
      dexamethasone. In situ hybridization and Western immunoblot assays were used to
      investigate the proinflammatory impact of SEB on IL-5 and granulocyte macrophage
      colony-stimulating factor (GM-CSF) mRNA levels and protein production in HNEC.
      RESULTS: Results indicate (1) stimulation of HNEC with SEB resulted in increased
      IL-5 and GM-CSF expression, which could be suppressed by dexamethasone (p <
      0.05), and SEB at concentrations of 1-100 ng/mL effectively promoted IL-5 and GM
      CSF release by HNEC (p < 0.05); (2) patients with CRSwNP showed a significantly
      increased expression of IL-5 and GM-CSF in HNEC than patients without CRSwNP (p <
      0.05); and (3) the expression of IL-5 and GM-CSF was significantly up-regulated
      under the stimulus of SEB compared with IL-1beta (p < 0.05). CONCLUSION: SEB acts
      as a superantigen and exhibits a dramatic proinflammatory impact on HNEC, which
      can be inhibited by the addition of glucocorticoid.

PMID- 19379607
TI  - Mucosal eosinophils and l-selectin ligands are associated with invasive and
      noninvasive sinus surgery outcomes.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by persistent
      inflammation of the nasal and paranasal mucosa with numerous emigrated
      leukocytes. L-Selectin on leukocytes and its endothelial glycosylated ligands
      initiate leukocyte infiltration into inflamed tissues. Endoscopic sinus surgery
      (ESS) is the major approach for restoring sinus physiology after failure of
      conservative therapy; however, the effect of enlarging the maxillary sinus ostium
      is still unknown. Here, we compared two histological markers of local
      inflammation, the number of mucosal eosinophils, and the expression of
      endothelial L-selectin ligands, with clinical outcomes after enlarging or saving
      the maxillary sinus ostium. METHODS: Twenty-three patients with CRS underwent
      uncinectomy on one side and additional middle meatal antrostomy on the other
      side. Maxillary sinus mucosa biopsy specimens from these patients and nine
      healthy subjects were taken for immunohistochemical evaluations of the number of
      mucosal eosinophils and endothelial L-Selectin ligands. Also, symptoms and
      mucociliary clearance were measured. RESULTS: The postoperative reduction of the
      endothelial L-Selectin ligands was independent of the operation technique. There
      was a correlation between postoperative number of mucosal eosinophils and symptom
      score, which was also independent of the surgical technique. The postoperative
      decrease of mucosal eosinophils, as well as the correlation of the intraoperative
      eosinophils with the postoperative symptom score, was found only on antrostomy
      side. CONCLUSION: ESS decreases the expression of endothelial L-Selectin ligands,
      which might lead to decreased eosinophil traffic into maxillary sinus mucosa,
      putatively more when enlarging the maxillary sinus ostium. Both intra- and
      postoperative low number of eosinophils seem to be indicators of good subjective
      recovery.

PMID- 19379608
TI  - Down-regulation of gp130 in nasopharyngeal carcinoma.
AB  - BACKGROUND: The purpose of this study was to explore the expression and
      biological functions of glycoprotein 130 (gp130) in Epstein-Barr virus (EBV)
      associated nasopharyngeal carcinoma (NPC). A prospective study was performed.
      METHODS: Ten patients with NPC and 10 patients with nasopharyngeal lymphoid
      hyperplasia (LH) were enrolled in this study. The transcripts of IL-27 receptors
      (gp130 and WSX-1) in the biopsy specimens derived from NPC were compared with
      that from LH by using reverse-transcription polymerase chain reaction. Cell lines
      including EBV(-), Burkitt-like lymphoma (BJAB) cells, human adult peripheral
      blood mononuclear cells, and lymphoblastoid cell lines were used to provide
      evidence of the biological function of gp130. In addition, killing assay for
      natural killer (NK) cells was performed in the presence of gp130. RESULTS: There
      was significantly stronger expression of gp130 on the LH specimens than on the
      NPC specimens. The levels of gp130 mRNA were reduced in the EBV-transformed
      cells. The cytotoxicity ratio against gp130-deficient B cells was diminished
      compared with gp130-existent B cells. CONCLUSION: The expression of gp130 is down
      regulated in patients with NPC. We presume that EBV controls the functions of NK
      cells through regulation of gp130 cytokine receptor.

PMID- 19379609
TI  - Validating the use of report-derived Lund-MacKay scores.
AB  - BACKGROUND: The Lund-MacKay score (LMS) is the standard for communicating
      radiological extent of chronic rhinosinusitis in research. However, retrospective
      analyses are often hindered by a substantial lack of radiological data.
      Calculating LMS from radiologists' reports may overcome this but has not been
      formally validated. METHODS: Twenty South Australian and 20 Texan patients with
      varying degrees of sinus disease were randomly chosen to undergo analysis. CT
      derived LMSs were calculated directly by two expert rhinologists at each
      institution and compared with scores derived solely from accompanying radiology
      reports by two blinded reviewers. RESULTS: The total LMS obtained via the expert
      rhinologists correlated very highly with that obtained from radiology reports
      (Spearman rank correlation, 0.75-0.88; p < 0.001). However, when individual
      sinuses were specifically analyzed, the correlation was highly variable.
      CONCLUSION: The results show that in both South Australian and Texan tertiary
      rhinology centers, radiologists' reports can be reliably used to calculate the
      total LMS.

PMID- 19379610
TI  - Diagnostic and staging accuracy of magnetic resonance imaging for the assessment
      of sinonasal disease.
AB  - BACKGROUND: Concerns over radiation exposure with paranasal sinus computed
      tomography (CT) have recently evolved. Magnetic resonance imaging (MRI) may be
      more advantageous in this regard, but the diagnostic assessment of MRI in chronic
      rhinosinusitis (CRS) has not been reported. The purpose of this study was to
      determine the correlation between CT- and MRI-based staging and diagnosis of CRS.
      METHODS: Paired CT and MRI scans of 89 adult patients who were imaged by both
      modalities within a 3-month time period for evaluation of pituitary disease were
      scored for sinus disease using the Lund-Mackay system in a randomized and blinded
      fashion. The Lund scores were compared for similarity, correlation, and
      diagnostic classification between modalities. RESULTS: The mean Lund scores were
      2.3 +/- 0.6 (95% CI) for CT-based staging and 2.1 +/- 0.5 for MRI-based staging
      with a median time interval between scans of 3 days. The difference means was not
      statistically significant (p = 0.444, paired t-test). Correlation analysis
      revealed a significant association between CT- and MRI-based scores (Pearson's r
      = 0.837, p < 0.001). Disease classification agreement analysis using published
      Lund score cutoffs (3 versus 4) for the likelihood of true sinus disease revealed
      that CT- and MRI-based scoring agreed on 76 cases (85.4%). Disagreement occurred
      in 13 cases (kappa: 0.557, p < 0.001). Sensitivity, specificity, positive
      predictive value, and negative predictive value were 66.7, 90.1, 63.2, and 91.4%,
      respectively. CONCLUSION: Lund-Mackay staging of sinus disease by MRI is closely
      correlated to corresponding staging based on CT. MRI does not significantly
      overstage or overclassify patients with sinus disease.

PMID- 19379611
TI  - Validation of the Sino-Nasal Outcome Test 20 (SNOT-20) domains in nonsurgical
      patients.
AB  - BACKGROUND: The objectives of this study were, first, to confirm the presence of
      multiple domains within the Sino-Nasal Outcome Test 20 (SNOT-20) using a
      medically treated population, and, second, to reanalyze data from this population
      to reveal incremental information. A prospective, randomized controlled trial was
      performed. METHODS: One hundred twenty-seven adults with chronic rhinitis or
      rhinosinusitis symptoms were treated with nasal saline irrigation or spray.
      Treatment outcome was quality of life measured with SNOT-20 scores, which were
      reanalyzed for this study with a factor analysis. Differences in change scores
      were compared. RESULTS: Factor analysis confirmed the presence of four domains:
      psychological function, sleep function, rhinological symptoms, and ear and/or
      facial symptoms. At 8 weeks after randomization, saline irrigation had
      significant effects on the rhinological symptom (p = 0.01) and sleep (p = 0.01)
      compared with saline spray, but no between-group difference was seen in
      psychological function or ear and/or facial symptom domains. CONCLUSION:
      Subscales identified differences in the impact of two medical interventions on
      chronic sinonasal symptoms. Reporting subscale scores might improve the precision
      of the SNOT-20 instrument, allowing discrimination between various treatments and
      their differential impact on sinonasal quality of life.

PMID- 19379612
TI  - Effects of an LL-37-derived antimicrobial peptide in an animal model of biofilm
      Pseudomonas sinusitis.
AB  - BACKGROUND: LL-37, an innate immunity protein expressed within sinonasal mucosa,
      has in vitro antibacterial and antifungal properties as well as efficacy against
      preformed Pseudomonas aeruginosa biofilms. We hypothesize that a 24 amino acid
      peptide derivative of LL-37 will show efficacy against biofilm-forming P.
      aeruginosa in an established animal model of sinusitis. METHODS: Five groups of
      six New Zealand rabbits were each infected with P. aeruginosa (PAO-1) and fitted
      with irrigating catheters 7 days later. Each group was instilled with either one
      of three different concentrations of peptide, a positive control of topical
      tobramycin, or the carrier solution without the peptide once a day for 10 days.
      Nasal diluent was collected throughout the irrigation period to assess for
      persistence or resolution of infection by determining colony-forming units (CFU).
      At study end, sinus mucosa was harvested for histological assessment of
      inflammation and SEM evaluation for ciliary integrity and presence of biofilms.
      RESULTS: Topical tobramycin at 400x minimum inhibitory concentration and 2.5
      mg/mL of peptide were effective in significantly lowering CFUs after 10 days of
      irrigation. Histological evaluation showed increased signs of inflammation in a
      dose-dependent manner within mucosa and bone of the groups receiving the peptide.
      SEM analysis showed ciliary loss in a dose-dependent manner. Biofilms were
      present in all groups except for the highest concentration of peptide and
      tobramycin. CONCLUSION: High concentrations of LL-37-derived peptide showed in
      vivo ability to eradicate Pseudomonas biofilms and decrease bacterial counts.
      However, increasing concentrations of peptide showed proinflammatory and
      ciliotoxic effects on sinus mucosa.

PMID- 19379613
TI  - Correlation of severity of epistaxis with nasal telangiectasias in hereditary
      hemorrhagic telangiectasia (HHT) patients.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu
      Osler-Weber syndrome, is an autosomal dominant disease that leads to
      multiregional angiodysplasia. The presence of telangiectasias in nasal mucosa
      leads to recurrent epistaxis that affects up to 96% of patients but with
      unpredictable severity. Some authors have previously explained that endonasal
      morphology and distribution of telangiectasias can be variable too. The purpose
      of this study was to evaluate any possible relationship between the severity of
      epistaxis and the different morphology and distribution of nasal telangiectasias
      in HHT patients. METHODS: A review was performed of nasal endoscopy records of 76
      consecutive HHT patients treated for epistaxis between 2003 and 2007 at our
      institution. An evaluation was performed of severity of epistaxis in the same
      patient group using a questionnaire and considering frequency, intensity,
      duration of nosebleeds, and need for blood transfusions. Comparison of data
      collected on morphology and distribution of nasal telangiectasias with data
      collected on severity of epistaxis was performed. RESULTS: Morphology and
      distribution of nasal telangiectasias showed a statistically significant
      correlation with frequency and intensity of epistaxis. Presence of
      telangiectasias endoscopically appearing as large and prominent correlates with
      higher frequency of epistaxis. An increase in number of nasal subsites involved
      correlates with higher intensity of nosebleeds. CONCLUSION: Our data suggest that
      to reduce frequency and intensity of epistaxis in HHT patients, treatments should
      be directed also at lesions located in the posterior part of nasal fossae and
      especially on telangiectasias endoscopically appearing as large and prominent.

PMID- 19379614
TI  - Use of complementary and alternative medicine by patients attending a rhinology
      outpatient clinic.
AB  - BACKGROUND: There are 50,000 practitioners of complementary and alternative
      medicine (CAM) within the United Kingdom. The current U.K. prevalence of CAM use
      is reported to be 25% and is rising. The national expenditure on CAM is an
      estimated pound1.6 billion. The aim of this study was to explore the pattern of
      CAM use in patients attending a rhinology outpatient clinic in Aberdeen. METHODS:
      Questionnaires were provided to 100 patients over a 2-month period. The
      questionnaire consisted of demographic sections and whether they had ever used
      CAM from a list of 49 herbal and nonherbal alternative therapies. Subjects were
      also asked why they used CAM, where they learned of CAM, whether they found it
      efficacious, and whether their general practitioner was aware they were using it.
      RESULTS: One hundred subjects completed questionnaires. Patients attending the
      clinic were suffering from the most common rhinological complaints including
      rhinosinusitis and nasal polyps. Sixty-five percent of patients had ever used
      CAM. Women were statistically significantly more likely to use CAM than men (p =
      0.012). Patients who were employed were more likely to use CAM, but there was no
      significant difference in CAM usage depending on marital status, social class,
      and age. Only 6% of patients felt CAM use was definitely ineffective. Only 43% of
      users of CAM had informed their doctor about its use. CONCLUSION: CAM usage is
      growing in popularity. All health care professionals should be aware of this and
      of the potential for adverse drug reactions occurring. The dangers of
      noncompliance with conventional medications should be emphasized to CAM users.

PMID- 19379615
TI  - Preoperative prognostic factors for olfactory change after functional endoscopic
      sinus surgery.
AB  - BACKGROUND: Functional endoscopic sinus surgery (FESS) has been considered to
      improve the olfactory function in patients with chronic rhinosinusitis. However,
      which factors might affect the olfactory outcome after FESS has not been well
      investigated. METHODS: A total of 70 patients with chronic rhinosinusitis who
      underwent FESS were enrolled in the study. The potential prognostic factors for
      improvement in olfaction after FESS were evaluated in these patients. On the day
      before FESS, the olfactory function was evaluated by a symptom score, a phenyl
      ethyl alcohol odor detection threshold test, the University of Pennsylvania Smell
      Identification Test, and a short-term odor memory/discrimination test, and were
      reevaluated by the same methods 6 months after FESS. RESULTS: The degree of nasal
      obstruction, the second minimal cross-sectional area measured by acoustic
      rhinometry, computed tomography scores before FESS, the degree of preoperative
      olfactory loss indicated by threshold and identification scores, and coexistence
      of nasal polyps or allergic rhinitis were not significantly reliable to influence
      the rates of olfactory improvement after FESS. CONCLUSION: Degree of nasal
      obstruction, extent of rhinosinusitis disease, and coexistence of nasal polyps or
      allergic rhinitis did not predicate the overall possibility of any olfactory
      improvement after FESS.

PMID- 19379616
TI  - The efficacy of a novel chitosan gel on hemostasis after endoscopic sinus surgery
      in a sheep model of chronic rhinosinusitis.
AB  - BACKGROUND: Postoperative bleeding remains a major problem after endoscopic sinus
      surgery (ESS). Patients who continue to bleed after ESS are at risk of airway
      compromise from inhalation of blood clots or from aspiration of blood-stained
      vomitus. The aim of this study was to determine the in vivo efficacy of a novel
      gel on hemostasis after ESS in a sheep model of chronic rhinosinusitis. METHODS:
      Twenty-one sheep infested with Oestrus ovus underwent ESS with standardized
      mucosal injuries created at the anterior ethmoid region using a microdebrider.
      Immediately after injury a baseline bleeding time was taken using the Boezaart
      Surgical Field Grading Scale. Computer randomization was performed to either
      receive chitosan/dextran (CD) gel or no treatment (control). Boezaart bleeding
      scores were calculated for each side every 2 minutes. Each postoperative day
      videoendoscopy was performed to document crusting/CD gel dissolution. RESULTS:
      The CD gel side was significantly more hemostatic at 2, 4, and 6 minutes after
      injury. Average time to hemostasis was significantly better for the intervention
      side versus control side, 4.09 (+/-1.61) versus 6.57 (+/-2.20), respectively (p =
      0.049). Complete hemostasis occurred by 6 minutes for all CD gel sides; however,
      control side bleeding was noted on three sides at 8 minutes and on one side at 10
      minutes. There was no significant difference in crusts scores at days 1, 3, 7,
      and 14. CONCLUSION: In the sheep model of ESS, CD gel significantly improved
      hemostasis compared with the control at 2, 4, and 6 minutes after mucosal injury.

PMID- 19379617
TI  - Chitosan glycerophosphate-based semirigid dexamethasone eluting biodegradable
      stent.
AB  - BACKGROUND: Chitosan is a polysaccharide derived from chitin deacetylation, which
      can form a biodegradable matrix capable of reversibly binding dexamethasone. The
      purpose of this study was to optimize the chitosan formulation to produce a
      pliable sheet, to assess the innate longevity and inflammatory potential of the
      polymer, and to study the in vivo rate of dexamethasone release over time.
      METHODS: Chitosan glycerophosphate (CGP) sheets were produced with varying
      degrees of deacetylation (70-100%) and analyzed for structural integrity. Two
      squared centimeter sheets of 91.7% deacetylated CGP were mixed with dexamethasone
      and implanted in 12 rabbit maxillary sinuses. Nasal lavage and peripheral blood
      samples were tested for dexamethasone levels by enzyme-linked immunosorbent assay
      (ELISA) over 15 days. Sinuses were examined histologically on postoperative days
      3, 7, and 15 for persistence of the stent and degree of inflammation when
      compared with CGP alone. RESULTS: The 91.7% deacetylated CGP formulation was
      found to have optimal mechanical properties and remained present with moderate
      degradation and negligible inflammation through postoperative day 15.
      Dexamethasone levels were detectable in nasal lavage and blood samples through
      postoperative day 15 and decayed over time (lavage: day 0, 7.70 +/- 0.97 ng/mL,
      and day 15, 2.53 +/- 1.71 ng/mL; blood: day 3, 2.51 +/- 0.14 ng/mL, and day 15,
      1.70 +/- 0.36 ng/mL). CONCLUSION: CGP may be used to create a semirigid sheet
      that is malleable, inert, and capable of eluting steroid over 15 days when
      implanted intranasally. This material may be used to create a pharmacologically
      active stent that spontaneously degrades over time.

PMID- 19379618
TI  - Effect of carboxymethylcellulose nasal packing on wound healing after functional
      endoscopic sinus surgery.
AB  - BACKGROUND: Functional endoscopic sinus surgery (FESS) has become the treatment
      of choice for patients with medically resistant chronic rhinosinusitis. Nasal
      packing is usually placed after the surgery to support wound healing and prevent
      adhesions. The purpose of this study was to investigate the effect of carboxy
      methylated cellulose (CMC) nasal packing on wound healing after FESS compared
      with no nasal packing. METHODS: Twenty-six patients underwent bilateral FESS. The
      patients were randomized to receive CMC mesh or gel packing on one side and no
      packing on the opposite side. The patients were followed at 2, 4, and 12 weeks
      after surgery. Endoscopically visible CMC, crusting, mucosal integrity, synechia
      formation, granulation tissue formation, and adverse side effects were assessed
      and documented. RESULTS: No adverse side effects were observed. No significant
      differences were found between the CMC-packed side and the unpacked side with
      respect to the outcome measure of wound healing. No difference was found between
      two different forms of CMC in terms of wound healing. Two weeks after surgery,
      endoscopically visible CMC was detected in four patients of the CMC mesh group,
      whereas none of the patients in the CMC gel group had endoscopically visible CMC
      (p = 0.040). CONCLUSION: As we were unable to establish an effect, we must
      question the efficacy of this packing material and the necessity of its use after
      FESS based on the technique of the Graz University Medical School. The mesh form
      of CMC could be potentially useful as a vehicle for extended drug delivery owing
      to its longer retention time in the nose.

PMID- 19379619
TI  - Efficacy of different techniques of sinonasal irrigation after modified Lothrop
      procedure.
AB  - BACKGROUND: Postoperative irrigation after endoscopic sinus surgery and
      endoscopic modified Lothrop procedure is used to remove nasal crusts and to
      improve wound healing. To evaluate the optimal application protocol for
      irrigation of the frontal sinus, a prospective cadaver study was performed.
      METHODS: An endoscopic modified Lothrop procedure and complete
      sphenoethmoidectomy were performed in 19 heads. Each was irrigated with a 1.5%
      solution of water and different colors using nasal spray and a squeeze bottle
      filled with 50, 100, and 200 mL. Intensity of local staining and percentage of
      area were documented using standardized videoendoscopy after irrigation in
      "bending over the sink" or "vertex to floor" position. Grading was performed by
      two independent observers for 23 anatomic regions, including the stained
      circumference of maxillary and frontal ostia. To evaluate the influence of the
      anatomy, acoustic rhinometry was performed. ANOVA was used to evaluate effects of
      application methods and head positions using GenStat 8.2 (Lawes Agricultural
      Trust, Rothamsted Experimental Station, Harpenden, U.K.) using an appropriate
      block structure. RESULTS: With regard to the frontal sinus, we were able to show
      clear superiority of the squeeze bottle technique filled with 200 mL and applied
      in the "vertex to floor position." CONCLUSION: In a relatively fit and flexible
      patient the vertex to floor position using a squeeze bottle technique is
      advocated. There may be some patients, however, for whom this position is not
      feasible. In these patients "bending over the sink," while inferior to the
      "vertex to floor" position, still ensures some irrigation of the frontal sinus.

PMID- 19379620
TI  - Endoscopic endonasal resection of esthesioneuroblastoma: a multicenter study.
AB  - BACKGROUND: This study reports the combined experience of the University of Miami
      and University of Pittsburgh with endoscopic endonasal resection of
      esthesioneuroblastoma (ENB). A retrospective case series review was performed in
      a tertiary care university hospital. METHODS: Twenty-three patients, 16 men and 7
      women, were reviewed. Mean age was 56.6 years (15-79 years). Nineteen patients
      received primary endoscopic endonasal anterior skull base resection. Of these,
      the modified Kadish stage at presentation was A in 2 patients, B in 11 patients,
      C in 5 patients, and D in 1 patient. Three patients had revision surgeries for
      recurrent tumors. The main outcome measures were complete resection and margin
      assessment, short-term and long-term complications, and recurrence rate. RESULTS:
      Complete resection and negative intraoperative resection margins were achieved
      endoscopically in 17 of the primarily treated cases. The two other cases had one
      patient that required an additional craniotomy approach to complete the resection
      of a positive lateral dual margin, another patient had positive margins at the
      orbital apex. All patients tolerated the endoscopic procedure very well with no
      meningitis. There were four cerebral spinal fluid leaks. Mean follow-up period
      for the primarily treated cases was 45.2 months (11-152 months), all were disease
      free at the most recent available follow-up. CONCLUSION: In experienced hands and
      carefully selected patients, endoscopic resection of ENB respects the principles
      of oncologic surgery, providing an adequate exposure for margin assessment as
      well as reliable reconstruction of the anterior skull defect with a relatively
      low morbidity.

PMID- 19379621
TI  - Juvenile nasopharyngeal angiofibroma: The expanded endonasal approach.
AB  - BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a benign but locally
      aggressively vascular tumor that may involve the skull base and extend
      intracranially. Endoscopic excision has become the new standard for smaller
      tumors but remains a challenge for large tumors, leading some to advocate
      radiation therapy. We reviewed our experience managing JNA, specifically with
      respect to utility of the expanded endonasal approach (EEA) for lesions with
      skull base and intracranial extension. METHODS: All cases of JNA at the
      University of Pittsburgh Medical Center from 1995 to 2006 were reviewed with
      respect to tumor size and location, vascular supply and results of embolization,
      skull base involvement and intracranial extension, surgical approach, blood loss,
      intraoperative and postoperative complications, and recurrence. RESULTS: Thirty
      one cases of JNA were identified. The majority of tumors were completely excised
      using the EEA, regardless of size or extension into adjacent compartments.
      Surgical excision of some tumors with intracranial blood supply was staged.
      Recurrence rates were not associated with extent of tumor or surgical technique.
      Long-term morbidity was minimal. CONCLUSION: Most JNA, regardless of tumor
      extent, may be completely excised using EEA alone or in combination with minor
      sublabial incisions avoiding the morbidity associated with larger open approaches
      or postoperative radiation therapy.

PMID- 19379622
TI  - Endoscopic approach to the infratemporal fossa for treatment of invasive fungal
      sinusitis.
AB  - BACKGROUND: Invasive fungal sinusitis is a progressive disease that can often
      extend beyond the nasal cavities and paranasal sinuses into surrounding soft
      tissue and bone. Aggressive antifungal therapy and surgical debridement are the
      mainstays of management. The pterygopalatine fossa and infratemporal fossa are
      two regions that are commonly involved in patients with invasive fungal
      sinusitis. When fungal disease extends to the infratemporal fossa, surgical
      debridement can be challenging. Traditionally, open approaches have been used for
      the management of disease in these areas. Advances in endoscopic skull base
      surgery may allow for less invasive approaches for the management of disease in
      the infratemporal fossa. This article describes a transnasal endoscopic approach
      to the infratemporal fossa for debridement of invasive fungal sinusitis. METHODS:
      Patients with invasive fungal sinusitis extending into the infratemporal fossa
      were treated with endoscopic debridement. Records of these patients were
      reviewed. RESULTS: Endoscopic debridement was performed in four patients with
      infratemporal fossa extension of invasive fungal sinusitis. Responsible organisms
      included Aspergillus, Mucor, and Candida. Adequate access and excellent
      visualization of the infratemporal fossa were obtained in all patients. The
      endoscopic anatomy and surgical technique are presented. CONCLUSION: Endoscopic
      approaches have been used to manage a variety of disease processes that extend
      beyond the confines of the paranasal sinuses. Invasive fungal sinusitis disease
      with extension into the infratemporal fossa can be safely debrided via a
      transnasal endoscopic technique. The approach provides excellent visualization
      with low morbidity.

PMID- 19379623
TI  - Ultrasonographic monitoring of implant thickness after augmentation rhinoplasty
      with expanded polytetrafluoroethylene.
AB  - BACKGROUND: Expanded polytetrafluoroethylene (ePTFE), or Gore-Tex (W.L. Gore &
      Associates, Flagstaff, AZ), is widely used in augmentation rhinoplasty, and the
      histological changes that it undergoes in the human body have been studied for
      decades. However, changes in the thickness of ePTFE after its use in augmentation
      rhinoplasty with a noninvasive object method are not well understood. METHODS: We
      report the results of 19 patients (10 male and 9 female patients) who had
      undergone an uncomplicated augmentation rhinoplasty with Gore-Tex.
      Ultrasonography was used to evaluate changes in the thickness of Gore-Tex
      implants and to detect inflammatory reactions around the implants 9-67 months
      after surgery. RESULTS: Gore-Tex implants were clearly distinguishable from the
      surrounding tissue with ultrasonography. The postoperative thickness of the
      implant was decreased by 29%. There was no significant correlation between the
      degree of change in implant thickness and the length of time after surgery.
      However, the amount of thickness reduction was associated with the implant's
      initial thickness at the time of the surgery (R = 0.448; p = 0.001). In addition,
      four patients (21%) showed fibrosis or granuloma formation around the implant
      that was detectable via ultrasonography. CONCLUSION: Gore-Tex implants lost
      thickness after nasal dorsal augmentation in proportion to their initial
      thickness, and ultrasonography was useful for evaluating changes in Gore-Tex
      thickness.

PMID- 19379624
TI  - In-office surgical repair of nasal valve stenosis.
AB  - BACKGROUND: Nasal valve (NV) stenosis is a well-known cause of nasal obstruction
      (NO) and congestion but it is often overlooked because the typical surgical
      therapies are complex and often associated with cosmetic changes. A simplified
      surgical procedure is needed to address straightforward stenosis of the NV in
      patients with no need of cosmetic improvement or cartilage grafting. The purpose
      of this article is to describe a simplified surgical procedure to relieve
      symptoms of NO without extensive surgical dissection, sedation, cartilage
      grafting, or cosmetic change. METHODS: This article describes a retrospective
      consecutive case series of patients that underwent a surgical procedure to
      correct NV stenosis in the office setting. The procedure is described in detail
      along with patient outcome assessment using a visual analog scale of patient
      satisfaction and a questionnaire regarding perceived postoperative cosmetic
      changes. RESULTS: Of 190 patients that underwent the procedure, 36 were done in
      the office setting and 28 completed the questionnaires. Six patients (21%)
      reported an improvement score of 10, a score of maximal improvement in breathing.
      The mean breathing score was 4.4, indicating an overall improvement in breathing
      ability after correction. No patient reported a major cosmetic change and three
      patients reported a subtle change. The remainder (89%) reported no perceived
      change in cosmesis. CONCLUSION: In-office surgical correction of the NV
      specifically targeting the mucosa, fibrous tissue, and caudal upper lateral
      cartilage was feasible, safe, and reliable in relieving complaints of NO due to
      uncomplicated NV stenosis.

PMID- 19379625
TI  - Rural health under attack.

PMID- 19379626
TI  - President's message. Reflections from Laos.

PMID- 19379627
TI  - Brief smoking cessation interventions by family physicians in northwestern
      Ontario rural hospitals.
AB  - INTRODUCTION: We report on physicians' beliefs, confidence and clinical practice
      relative to the provision of smoking cessation interventions in northwestern (NW)
      Ontario, where tobacco use and tobacco-related disease prevalence are high and
      smoking cessation services are scarce. METHODS: Physicians working at the 12
      rural hospitals in NW Ontario were eligible for inclusion in the study. Survey
      items included clinical practices based on the "5 A's" protocol for tobacco
      intervention, and beliefs about, confidence in, and barriers and facilitators to
      intervention. RESULTS: Physicians from 8 of the 12 hospitals responded. Almost
      all (> 91%) reported positive beliefs about providing smoking cessation
      interventions and were confident intervening. Relative to the 5 A's protocol for
      tobacco intervention, 100% of respondents ask, advise, assess and assist patients
      to quit smoking, and 89% arrange follow-up. The most frequent methods of
      assistance included pharmacotherapy, suggestions of specific actions to make it
      easier to quit and recommendations for alternatives to tobacco use. The most
      frequent barrier to intervenion was lack of time. DISCUSSION: Based on
      respondents' positive beliefs, confidence and current clinical practice relative
      to tobacco interventions, physicians in NW Ontario seem well positioned to play a
      key role in helping to reduce the high rates of tobacco use and tobacco-related
      diseases by providing smoking cessation interventions to patients who have been
      admitted to hospital.

PMID- 19379628
TI  - How important are out-of-pocket costs to rural patients' cancer care decisions?
AB  - OBJECTIVE: We examined the importance of 5 items (stage of illness, personal
      feelings, travel costs, drug costs and child care costs) in the cancer treatment
      decisions of urban and rural residents after they had started treatment for their
      cancer. METHODS: We surveyed 484 adults who presented for care at cancer clinics
      in Newfoundland and Labrador from September 2002 to June 2003. Respondents rated
      the importance of each of the 5 items in their cancer care decisions on a 5-point
      Likert scale, which was later collapsed into 2 categories, "important" and "not
      important." We used chi2 tests and multiple logistic regression to compare the
      responses of urban and rural residents. RESULTS: In our sample of 484
      respondents, there were 258 (53.3%) urban and 226 (46.7%) rural residents. After
      controlling for other significant predictors, we found that rural residents were
      more likely to report that travel costs (odds ratio [OR] 1.79, 95% confidence
      interval [CI] 1.21-2.63), drug costs (OR 1.69, 95% CI 1.13-2.23) and child care
      costs (OR 2.33, 95% CI 1.09-4.96) were "important" in cancer treatment decisions
      compared with urban residents. Stage of disease and personal feelings were
      equally important to urban and rural residents. CONCLUSION: Financial impediments
      disproportionately affect rural residents' decisions about cancer care and
      highlight the need to ensure that centralized specialist care, such as cancer
      treatment, is accessible.

PMID- 19379629
TI  - Prevalence of impaired glucose tolerance and the components of metabolic syndrome
      in Canadian Tsimshian Nation youth.
AB  - INTRODUCTION: Canadian Aboriginal people have been disproportionately affected by
      obesity and type 2 diabetes (T2D). Our objective was to determine the prevalence
      of obesity, glucose intolerance and the components of metabolic syndrome (MetS)
      in Tsimshian Nation youth living in 3 remote coastal communities. METHODS: A
      medical history, anthropometric measurements and an oral glucose tolerance test
      were performed in youth aged 6-18 years. We defined "overweight" by a body mass
      index (BMI) at the 85th percentile or higher and "obese" by a BMI at the 95th
      percentile or higher, by age and sex. We used the International Diabetes
      Federation criteria for MetS. RESULTS: Of the 224 eligible youth, 192 (85%)
      participated in the study. Nineteen percent were overweight, 26% were obese and
      36% had central obesity (waist circumference > or = 90th percentile for age and
      sex). No new cases of T2D were identified. The prevalence of impaired fasting
      glucose (IFG 5.6-6.9 mmol/L) and impaired glucose tolerance (IGT 2-hr glucose 7.8
      11.0 mmol/L) were 19.3% and 5.2%, respectively. Five of the 10 youth with IGT had
      a fasting glucose less than 5.6 mmol/L. The prevalence of MetS was 4.7% and
      increased to 8.3% when pediatric hypertension norms were applied. CONCLUSION:
      Tsimshian Nation youth have a high prevalence of central obesity, impaired
      glucose homeostasis and other components of MetS. The oral glucose tolerance test
      may be a more appropriate screening test to identify IGT in Aboriginal youth.

PMID- 19379630
TI  - The occasional acute application of continuous positive airway pressure.

PMID- 19379631
TI  - Country cardiograms case 33.

PMID- 19379632
TI  - Rural and remote obstetric care close to home: program description, evaluation
      and discussion of Sioux Lookout Meno Ya Win Health Centre obstetrics.
AB  - PROBLEM BEING ADDRESSED: Aboriginal and non-Aboriginal women in rural and remote
      settings struggle to access obstetric care close to home. Objective of the
      program: To deliver a full range of modern and safe obstetric care to 28 remote
      Aboriginal communities served by rural-based health care. PROGRAM DESCRIPTION:
      Rural family physicians provide intrapartum, cesarean delivery and anesthesia
      services to 350 rural, primarily Aboriginal women in a collegial, supportive
      environment. CONCLUSION: Rural and remote obstetric services need support before
      they fail. Patient volume, remote location and organizational culture are key
      elements. Evidence teaches us that outcomes are best when women deliver closer to
      home.

PMID- 19379634
TI  - The use of echocardiography in predicting heart failure in patients with coronary
      artery disease.

PMID- 19379635
TI  - Invasive monitoring in patients with heart failure.
AB  - The syndrome of heart failure is characterized by symptoms that are relatively
      insensitive and nonspecific. Physical diagnosis may be unreliable even in the
      hands of experienced clinicians, despite the presence of significantly elevated
      filling pressures or a significantly depressed cardiac output. Instrumentation
      and devices such as the insertion of a pulmonary artery catheter and the
      implantable hemodynamic monitor have a major role in the diagnosis and management
      of cardiovascular disease. They provide a means of measuring intracardiac
      pressures for point-in-time measurements (cardiac catheterization), short term in
      an acute situation (insertion of a pulmonary arterial catheter), and, more
      recently, a long-term assessment increasing our understanding of the nuances of
      the hemodynamic derangements associated with heart failure and other conditions.
      With improved ability to accurately assess and monitor filling pressures,
      clinicians can more precisely adjust therapy with the goal of improving patient
      symptoms and possibly outcomes.

PMID- 19379636
TI  - Cardiac dysfunction induced by novel targeted anticancer therapy: an emerging
      issue.
AB  - Increasing use of targeted anticancer agents that inhibit tyrosine kinase
      signaling (monoclonal antibodies or tyrosine kinase inhibitors) has dramatically
      improved the survival of patients with malignancies. However, cardiotoxicity,
      including heart failure, left ventricular dysfunction, hypertension, myocardial
      infarction, and thromboembolism, has occurred. Importantly, these
      cardiotoxicities are at least partially reversible and responsive to medical
      management. Early recognition of cardiovascular side effects is vital to allow
      long-term, continuous therapy with these life-prolonging agents. This article
      reviews potential cardiovascular side effects of frequently used inhibitors of
      tyrosine kinase activity (eg, trastuzumab, sunitinib) and discusses the diagnosis
      and management of cardiotoxicity associated with targeted therapy.

PMID- 19379637
TI  - Cardiac resynchronization therapy in NYHA class IV heart failure.
AB  - Clinical practice guidelines recommend cardiac resynchronization therapy (CRT)
      for ambulatory New York Heart Association (NYHA) class IV patients with a QRS
      duration >or= 120 ms and a left ventricular ejection fraction <or= 35%. Only two
      prospective, randomized trials have compared outcomes after CRT in NYHA class III
      and IV patients. CRT improved mortality, exercise capacity, and quality of life
      in class IV patients, but the 1-year mortality remained high. Patients in these
      trials were in sinus rhythm at randomization and most patients had a left bundle
      branch block. Less data are available for NYHA class IV patients with atrial
      fibrillation, right bundle branch block, and previous ventricular pacing. No
      prospective randomized data are available for the use of CRT as rescue therapy in
      inotrope-dependent patients, but several case series have reported promising
      results. It is likely that "rescue therapy" with CRT will be most beneficial when
      patients improve enough with CRT to allow reinstitution of angiotensin-converting
      enzyme inhibitors and beta blockers.

PMID- 19379638
TI  - End-of-life care in heart failure.
AB  - The clinical syndrome of heart failure is increasing in prevalence, as is the
      number of elderly persons with heart failure. Increasing frailty and progression
      of heart failure in large numbers of patients means clinicians are increasingly
      challenged to provide end-of-life care for heart failure patients. End-of-life
      care has been little studied, but management can be understood from early
      clinical trials of advanced heart failure. Evidence-based heart failure
      medications, including angiotensin-converting enzyme inhibitors and beta
      blockers, improve symptoms in patients with advanced heart failure and depressed
      ejection fraction and should usually be continued in end-stage disease. Patients
      also should have ongoing meticulous management of fluid status to maximize
      quality of life. End-of-life care should be planned with the patient and family
      and should incorporate comprehensive symptom management, bereavement support, and
      spiritual support. Ongoing communication with patients and families about
      prognosis can ease the planning of care when the end of life nears.

PMID- 19379639
TI  - Therapy for acute heart failure syndromes.
AB  - The pharmacologic management of acute heart failure syndromes (AHFS) has changed
      little over the past 15 years. Traditional therapies, such as nitrates and loop
      diuretics, remain the mainstay of therapy, with inotropes reserved for patients
      who present in shock or an advanced low-output state. We review the use of these
      therapies in AHFS with added insights from recent clinical trials and registry
      data.

PMID- 19379640
TI  - Added value of real-time three-dimensional echocardiography in assessing cardiac
      masses.
AB  - Echocardiography is the most common noninvasive tool used in assessing cardiac
      masses. Real-time three-dimensional echocardiography expands the diagnostic
      capabilities of cardiac ultrasound in assessing the location, composition, size,
      and relationship to other structures of cardiac masses. The improved
      characterization of the anatomy of the mass, in conjunction with the accurate
      calculation of the left ventricular ejection fraction, makes this new technology
      the imaging modality of choice in assessing cardiac masses.

PMID- 19379641
TI  - Intracardiac echocardiography for the guidance of percutaneous procedures.
AB  - Interventional cardiology has seen great advances in the past decade. A wide
      range of interventional procedures has been established as standard therapeutic
      modalities and more are yet to come. Multiple imaging modalities have been used
      to guide these procedures. Intracardiac echocardiography (ICE) provides an
      accurate imaging tool to guide the appropriate performance of many of these
      procedures. Early studies compared ICE as a new imaging modality to guide
      interventional closure of atrial communications with other more established
      imaging techniques, such as transesophageal echocardiography, with excellent
      accuracy. In this article, we discuss the value of using ICE in guiding some
      percutaneous interventional procedures. We also discuss the imaging protocol for
      using ICE to guide atrial level shunt device closure. Our experience in using ICE
      for guiding percutaneous valve placement is also discussed.

PMID- 19379642
TI  - Contrast echocardiography: an update.
AB  - Despite the advent of tissue harmonic imaging, echocardiography fails to produce
      diagnostically useful images in a significant proportion of patients. This often
      leads to inaccurate assessment of left ventricular function, necessitating the
      use of other, more expensive and laborious imaging techniques, purely for
      diagnostic purposes. This has facilitated the development of microbubbles, which
      together with ultrasound, produce opacification of the left ventricular cavity,
      thus enabling clear visualization and accurate quantification of left ventricular
      function. Contrast agents have also facilitated the development of myocardial
      contrast echocardiography. This allows assessment of cardiac anatomy, function,
      and perfusion, all in one sitting, by the bedside. Contrast ultrasound imaging
      also has now been applied to newer techniques (eg, real-time three-dimensional
      echocardiography) and is also showing promise in other cardiovascular scans (eg,
      carotid ultrasound for intima-media thickness). Thus, contrast agents play a
      pivotal role in noninvasive cardiovascular imaging and its use worldwide is
      likely to increase.

PMID- 19379643
TI  - Evaluation of left ventricular function using left ventricular twist and torsion
      parameters.
AB  - The left ventricular (LV) twist/torsion, wringing motion of the heart is a key
      element for regulating LV systolic and diastolic mechanics. Until recently, the
      evaluation of LV twist was limited to the research arena because of the
      requirement of invasive techniques or low availability of tagged MRI. The recent
      development of two-dimensional speckle tracking echocardiography enables the
      noninvasive measurement of LV rotation in humans. This article constitutes a
      practical guide for the measurement and interpretation of LV twist parameters
      using two-dimensional speckle tracking echocardiography and discusses its
      clinical usefulness for the evaluation of LV function.

PMID- 19379644
TI  - Modern evaluation of left ventricular diastolic function using Doppler
      echocardiography.
AB  - The evaluation of left ventricular (LV) diastolic function is an essential
      component of the echocardiographic examination for dyspneic patients with
      impaired or preserved LV systolic function. Doppler echocardiography in
      combination with two-dimensional echocardiographic findings can assist the
      diagnosis of underlying cardiac dysfunction, give an estimate of LV filling
      pressures, guide heart failure treatment, and provide important prognostic
      information. This article reviews the essentials of modern Doppler assessment of
      diastolic function and highlights recent updates, areas of controversy, and
      future applications.

PMID- 19379645
TI  - The cutaneous epidermal growth factor network: Can it be translated clinically to
      stimulate hair growth?
AB  - The influences exerted by the epidermal growth factor receptor (EGFR) on the skin
      act at multiple levels, which involve compartments that normally express EGFR.
      These include the basal and suprabasal layers of the epidermis, sebaceous glands,
      and the outer root sheath of the hair follicles. The physiological roles of EGFR
      ensure epidermal renewal and integrity, along with a gatekeeping and function and
      hair growth stimulation functions. Important cellular functions that are altered
      during EGF receptor blocking therapy consist of epidermal differentiation,
      proliferation, apoptosis, and migration, with an overall dominating effect of
      inducing growth arrest and terminal differentiation of the keratinocytes in the
      basal layers. The effects of EGFR blockage on the hair cycle include terminal
      differentiation of the hair follicle, which in certain cases may be associated
      with trichomegaly. Trichomegaly of the eyelashes may occur as an isolated
      occurrence or, frequently, as part of a generalized phenomenon that may be
      associated with the use of the EGFR inhibitors. Molecular changes associated with
      EGFR blockage are discussed, relevant to their association with hair growth.
      Modulation of Akt, AP2alpha, CDK4, Notch-1, p27KIP1, and Hedgehog expression are
      involved in the initiation of the hair cycle and inducement of the anagen phase,
      followed by proliferation and differentiation of the hair follicles. Epidermal
      growth factor receptor inhibitors have been developed as therapeutic molecules
      directed against cancer; in these regimens the knowledge of EGF receptor
      signaling functions has been translated into significant clinical results.
      However, among their various collateral effects on the skin, hair growth is
      observed to occur in certain patients. A particular "wavy" hair phenotype is
      observed during the pharmacological EGFR receptor blockade, just as in murine
      transgenic models that carry loss of function of TGF-alpha or EGFR genes. A
      better characterization of the individual roles pertaining to the EGF family
      ligands and receptors, has the potential provide new strategies for the
      management of hair loss.

PMID- 19379646
TI  - Cutaneous epithelioid angiomatous nodule: different views or interpretations in
      the analysis of ten new cases.
AB  - Classification schemes proposed for vascular lesions are the subjects of
      significant controversy. Cutaneous epithelioid angiomatous nodule (CEAN) was
      described in 2004, but there is no agreement as to whether this is a distinct
      entity or a type of either epithelioid hemangioma or angiolymphoid hyperplasia
      with eosinophilia. We present a typical case of CEAN and discuss nine other cases
      from our institution. We then provide two opposing viewpoints concerning its
      classification.

PMID- 19379647
TI  - Atypical histopathology in bowel-associated dermatosis-arthritis syndrome: A case
      report.
AB  - Bowel-associated dermatosis-arthritis syndrome (BADAS) is characterized by a
      prodrome of fever, chills, and flu-like symptoms with subsequent skin eruptions,
      myalgias, and polyarthralgias. The syndrome was initially described following
      jejunoileal bypass surgery for weight loss. Histopathology of the skin lesions
      present in BADAS is described in the literature as identical to that of Sweet
      syndrome. We present a patient whose clinical history and physical exam were
      consistent with the diagnosis of BADAS. Dermatopathology in this case
      demonstrated a large subcorneal pustule without a significant dermal neutrophilic
      infiltrate. The histologic differential included subcorneal pustular dermatosis,
      bullous impetigo, or IgA pemphigus. The histology in BADAS may not necessarily be
      identical to Sweet syndrome, and the clinical picture alone plays an important
      role in diagnosis. The correct diagnosis of BADAS prevents a myriad of laboratory
      tests and allows for more effective symptom management in this chronic condition.

PMID- 19379648
TI  - Persistent hair growth during treatment with the EGFR inhibitor erlotinib.
AB  - Medications belonging to the group of epidermal growth factor (EGFR) inhibitors
      are currently in widespread use for the treatment of epithelial malignancies.
      Many cutaneous side effects are known to develop as a result of the use of these
      agents. Trichomegaly is a newly described side effect, consisting of premature
      maturation (terminal differentiation) of the hair of the eyelashes and the scalp,
      which is characterized by a hairy phenotype. Although occurrence of the acneiform
      skin rash is clearly associated with favorable tumor responses and improvement in
      patient survival during the use of EGFR inhibitors for the treatment of cancer,
      the significance of trichomegaly is less clear. A review of all published cases
      is provided, leading to the observation that trichomegaly also developed in
      patients whose tumors had a positive response to anti-EGFR therapy. The apparent
      lack of the development of tolerance to this medication effect and, therefore,
      the continued clinical sign of trichomegaly is in contrast to the time-limited
      nature of other cutaneous side effects of EGFR inhibitors, such as the classical
      papulo-pustular rash. The persistence of trichomegaly in some patients brings
      into question the precise mechanism of this phenomenon and suggests the
      possibility of using EGFR inhibition therapeutically to stimulate hair growth.

PMID- 19379649
TI  - Subcorneal pustular dermatosis in a patient with rheumatoid arthritis and diffuse
      scleroderma.
AB  - We report a case of subcorneal pustular dermatosis (SPD) in a patient with
      rheumatoid arthritis (RA) and diffuse scleroderma. Although SPD has been
      described in association with RA, it has not been reported in association with
      diffuse scleroderma to our knowledge. This observation supports the hypothesis
      linking immune dysfunction as a common pathogenesis of these three entities.

PMID- 19379650
TI  - Atypical leiomyoma: An unusual variant of cutaneous pilar leiomyoma.
AB  - Cutaneous atypical leiomyoma is an unusual benign tumor arising from arrector
      pili muscle that shares histological features with uterine atypical or symplastic
      leiomyoma: atypical cellularity with pleomorphic nuclei but minimal or no
      mitosis. Six other cases have been reported so far and, in spite of its name and
      of being a smooth muscle proliferation, no recurrences nor metastasis have been
      reported.

PMID- 19379652
TI  - Sarcoidosis involving the lacrimal, submandibular, and parotid glands with panda
      sign.
AB  - Sarcoidosis is a granulomatous inflammation of unknown origin that varies in
      severity and distribution. We present a case of sarcoidosis with involvement of
      the skin, lacrimal, parotid, and submandibular glands. The patient had been
      previously misdiagnosed as having angioedema and allergic contact dermatitis; he
      had the rare finding of panda sign on gallium scintigraphy.

PMID- 19379651
TI  - Unilateral taxane-induced onychopathy in a patient with a brain metastasis.
AB  - Chemotherapy using taxanes have been useful in the treatment of several types of
      solid tumors. Nail abnormalities have been reported primarily with the use of
      docetaxel, but also with low dose, weekly paclitaxel. We report a patient with 20
      nail onycolysis associated with the use of paclitaxel that resolved after
      stopping the medication and then recurred after the use of docetaxel, but spared
      all the nails of a paretic hand.

PMID- 19379653
TI  - Non-healing perianal ulcer: A rare presentation of cutaneous tuberculosis.
AB  - Perianal tuberculosis is an extremely rare form of tubercular disease. We report
      here a case of chronic non-healing perianal tubercular ulcer associated with,
      asymptomatic pulmonary tuberculosis in a 16-year-old boy for its rarity and to
      emphasize the importance of considering tubercular etiology in the work up of
      persistent perianal ulcer.

PMID- 19379654
TI  - Rhinophymous leishmaniasis: A new variant.
AB  - Cutaneous leishmaniasis is known for its wide clinical spectrum. The nose is one
      of the usual sites where the disease can present in many forms, such as
      psoriasiform plaques, furunculoid nodules, lupoid plaques, and erysipeloid or
      mucocutaneous types. We present a new morphology, i.e. rhinophyma-like plaque in
      an elderly male patient who presented with a large infiltrated plaque involving
      his nose and the adjoining area of his upper lip. It appeared to be rhinophyma of
      the nose but was diagnosed as cutaneous leishmaniasis after the demonstration of
      leishmania parasites in a skin smear preparation; he was treated satisfactorily
      with antimonials.

PMID- 19379655
TI  - Success of prednisone in the treatment of a patient with sarcoidosis and systemic
      sclerosis: Report of a case.
AB  - We report a case of a man with sarcoidosis and diffuse systemic sclerosis who
      showed improvement of both diseases after prednisone therapy and remains
      asymptomatic after three years of follow-up. The association of these two
      diseases is rare and it is controversial whether this is a chance association or
      if there is a relationship between the two autoimmune diseases. Despite the poor
      prognosis and response to therapy of the patients with diffuse systemic
      sclerosis, our patient had a marked improvement of the disease with prednisone.

PMID- 19379656
TI  - Paramedian forehead flap thinning using a flexible razor blade.
AB  - Paramedian forehead flaps are sometimes required to resurface large or deep nasal
      defects. The flap often needs to be thinned to match the contour of the
      surrounding skin at the recipient site. We describe a technique to thin the
      distal potion of the paramedian forehead flap using a flexible razor blade, the
      Dermablade. Once familiar with it, this same technique may be applied to thin
      other interpolation flaps.

PMID- 19379657
TI  - Unknown: Erythematous nodules on the right cheek and chin.
AB  - Cutaneous metastases from internal malignancies are uncommon. We report on a 55
      year-old man who presented with cutaneous metastases from a squamous cell
      carcinoma of the lung. Chest x-ray and chest Computerized Axial Tomography (CT)
      revealed the lung tumor.

PMID- 19379658
TI  - Parable: from the gospel according to Saint Matthew.

PMID- 19379659
TI  - Case report: Fluocinonide-induced perioral dermatitis in a patient with
      psoriasis.
AB  - Topical corticosteroids are the primary treatment for psoriasis. A patient with
      psoriasis being treated with topical fluocinonide for lesions on the extremities
      developed an erythematous facial eruption consistent with perioral dermatitis.
      When topical agents are applied, they often end up in unintended areas. The
      potential for drug-induced perioral dermatitis should be considered in psoriasis
      patients treated with potent topical corticosteroids.

PMID- 19379660
TI  - Habit tic deformity secondary to guitar playing.
AB  - A 29-year-old man exhibited linear ridges of the right thumbnail that had been
      present for ten years. After he stopped playing the guitar for three months, the
      proximal portion of the abnormality cleared. Nail changes similar to the habit
      tic deformity may be produced by guitar playing.

PMID- 19379661
TI  - Pancreatic panniculitis: A rare form of panniculitis.
AB  - Pancreatic panniculitis is rare form of panniculitis with associated pancreatic
      disease. The skin manifestations can occur at any time of the pancreatic
      pathology. Here we report a case of pancreatic panniculitis associated with
      underlying chronic pancreatitis. The patient presented with painful subcutaneous
      nodules and the histology revealed the characteristic features of pancreatic
      panniculitis.

PMID- 19379662
TI  - Babesia and its hosts: adaptation to long-lasting interactions as a way to
      achieve efficient transmission.
AB  - Babesia, the causal agent of babesiosis, are tick-borne apicomplexan protozoa.
      True babesiae (Babesia genus sensu stricto) are biologically characterized by
      direct development in erythrocytes and by transovarial transmission in the tick.
      A large number of true Babesia species have been described in various vertebrate
      and tick hosts. This review presents the genus then discusses specific
      adaptations of Babesia spp. to their hosts to achieve efficient transmission. The
      main adaptations lead to long-lasting interactions which result in the induction
      of two reservoirs: in the vertebrate host during low long-term parasitemia and
      throughout the life cycle of the tick host as a result of transovarial and
      transstadial transmission. The molecular bases of these adaptations in vertebrate
      hosts are partially known but few of the tick-host interaction mechanisms have
      been elucidated.

PMID- 19379663
TI  - Perpetuation of Leishmania: some novel insight into elegant developmental
      programs.
AB  - Leishmania spp. are polarized single-celled eukaryotic parasites, the
      perpetuation of which relies on two other organisms they "use" as hosts. One of
      the Leishmania host organisms is a blood-feeding female sand fly, the second host
      being a mammal that acts as a blood source for the female sand fly. Leishmania
      hosting sand flies transmit the metacyclic promastigote developmental stage to
      the mammal skin. While many mammals are known to act as sand fly blood sources,
      only some of these mammals are/ will be "used" as Leishmania hosts. This host
      status means that skin as well as skin-distant tissues and cell lineages
      (mononuclear phagocytes and fibroblasts) of these mammals are rapidly and
      continuously remodelled as niches where Leishmania will deploy its developmental
      programs: it is noteworthy that without the deployment of the developmental
      program underlying Leishmania transmission from the mammal to the blood-searching
      and blood-feeding sand flies, the perpetuation of Leishmania will be suspended.
      While post genomic approaches are providing insight about some features of
      Leishmania major, Leishmania infantum/chagasi and Leishmania braziliensis, such
      approaches are not yet available for the natural hosts (wild rodents, wild sand
      flies) these Leishmania species "use" as hosts.

PMID- 19379664
TI  - Evidence of long distance airborne transport of porcine reproductive and
      respiratory syndrome virus and Mycoplasma hyopneumoniae.
AB  - The ability of porcine reproductive and respiratory syndrome virus (PRRSV) and
      Mycoplasma hyopneumoniae to be transported over long distances via the airborne
      route was evaluated. A source population of 300 grow-finish pigs was
      experimentally inoculated with PRRSV MN-184 and M. hyopneumoniae 232 and over a
      50-day period, air samples were collected at designated distances from the source
      herd using a liquid cyclonic collector. Samples were tested for the presence of
      PRRSV RNA and M. hyopneumoniae DNA by PCR and if positive, further characterized.
      Of the 306 samples collected, 4 (1.3%) were positive for PRRSV RNA and 6 (1.9%)
      were positive for M. hyopneumoniae DNA. The PRRSV-positive samples were recovered
      4.7 km to the northwest (NW) of the source population. Four of the M.
      hyopneumoniae-positive samples were obtained at the NW sampling point; 2 samples
      at approximately 2.3 km and the other 2 samples approximately 4.7 km from the
      source population. Of the remaining 2 samples, one sample was obtained at the
      southeast sampling point and the other at the southwest sampling point, with both
      locations being approximately 4.7 km from the source. The four PRRSV-positive
      samples contained infectious virus and were >/= 98.8% homologous to the MN-184
      isolate used to inoculate the source population. All 6 of the M. hyopneumoniae
      positive samples were 99.9% homologous to M. hyopneumoniae 232. These results
      support the hypothesis that long distance airborne transport of these important
      swine pathogens can occur.

PMID- 19379666
TI  - Proteomics makes progress in cartilage and arthritis research.
AB  - Understanding biology at the systems level is a powerful method for discovery of
      previously unrecognized molecular pathways and mechanisms in human disease. The
      application of proteomics to arthritis research has lagged behind many other
      clinical targets, partly due to the unique biochemical properties of cartilage
      and associated biological fluids such as synovial fluid. In recent years,
      however, proteomic-based studies in cartilage and arthritis research have risen
      sharply and have started to make a significant impact on our understanding of
      joint disease, including the discovery of new and promising biomarkers of
      cartilage degeneration, a hallmark of arthritis. In this review we will make the
      case for the ongoing proteomic analysis of cartilage and other tissues affected
      by joint disease, overview some of the core proteomic techniques and discuss how
      the challenge of cartilage proteomics has been met through technical innovation.
      The major outcomes and information obtained from recent proteomic analysis of
      synovial fluid, cartilage and chondrocytes will also be described. In addition,
      we present some novel insights into post-translational regulation of cartilage
      proteins, through proteomic identification of proteolytic fragments in mouse
      cartilage extracts and explant culture media. We conclude with our prediction of
      how emerging proteomic technologies that have yet to be applied in arthritis
      research are likely to contribute further important information.

PMID- 19379665
TI  - Genetic evidence for key roles of decorin and biglycan in dentin mineralization.
AB  - Targeted disruption of the dentin sialophosphoprotein (DSPP) gene in the mice
      (Dspp(-/-)) results in dentin mineralization defects with enlarged predentin
      phenotype similar to human dentinogenesis imperfecta type III. Using
      DSPP/biglycan (Dspp(-/-)Bgn(-/0)) and DSPP/decorin (Dspp(-/-)Dcn(-/-)) double
      knockout mice, here we determined that the enlarged predentin layer in Dspp(-/-)
      teeth is rescued in the absence of decorin, but not in the absence of biglycan.
      However, Fourier transform infrared (FTIR) spectroscopy analysis reveals similar
      hypomineralization of dentin in both Dspp(-/-)Bgn(-/0) and Dspp(-/-)Dcn(-/-)
      teeth. Atomic force microscopy (AFM) analysis of collagen fibrils in dentin shows
      subtle differences in the collagen fibril morphology in these genotypes. The
      reduction of enlarged predentin in Dspp(-/-)Dcn(-/-) mice suggests that the
      elevated level of decorin in Dspp(-/-) predentin interferes with the
      mineralization process at the dentin mineralization front. On the other hand, the
      lack of DSPP and biglycan leads to the increased number of calcospherites in
      Dspp(-/-)Bgn(-/0) predentin, suggesting that a failure in coalescence of
      calcospherites was augmented in Dspp(-/-)Bgn(-/0) teeth as compared to Dspp(-/-)
      teeth. These findings indicate that normal expression of small leucine rich
      proteoglycans, such as biglycan and decorin, plays an important role in the
      highly orchestrated process of dentin mineralization.

PMID- 19379667
TI  - Regulation of p38 MAP kinase by anastellin is independent of anastellin's effect
      on matrix fibronectin.
AB  - Anastellin is an angiogenesis inhibitor derived from the first type III repeat of
      fibronectin (FN). Anastellin binds to fibronectin and promotes the polymerization
      of soluble fibronectin into a highly polymerized form termed superfibronectin. In
      addition, anastellin also causes remodeling of pre-existing fibronectin matrix
      and modulates cell signaling pathways in both endothelial cells and fibroblasts.
      In the present study, we address the relationship of anastellin's effects on
      fibronectin matrix to its effects on p38 MAP kinase (MAPK) activation. Using a
      mutant form of anastellin which binds to fibronectin matrix, but does not
      stimulate formation of superfibronectin, we demonstrate that the activation of
      p38 MAPK by anastellin is not dependent on the formation of superfibronectin. The
      mutant form of anastellin does stimulate matrix remodeling, but experiments using
      FN(-/-) cells show that the effect of anastellin on p38-MAPK activation is
      completely independent of fibronectin. Anastellin was able to activate p38 MAPK
      on cells in suspension as well as on cells null for beta1 integrins, suggesting
      that anastellin activity did not require ligation of integrins. These data
      suggest that the activation of p38 MAPK by anastellin is independent of
      anastellin's effects on fibronectin matrix organization.

PMID- 19379668
TI  - Mice that lack matrix metalloproteinase-9 display delayed wound healing
      associated with delayed reepithelization and disordered collagen fibrillogenesis.
AB  - Matrix metalloproteinase- (MMP-9) is involved in processes that occur during
      cutaneous wound healing such as inflammation, matrix remodeling, and
      epithelialization, To investigate its role in healing, full thickness skin wounds
      were made in the dorsal region of MMP-9-null and control mice and harvested up to
      14 days post wounding. Gross examination and histological and immunohistochemical
      analysis indicated delayed healing in MMP-9-null mice. Specifically, MMP-9-null
      wounds displayed compromised reepithelialization and reduced clearance of fibrin
      clots. In addition, they exhibited abnormal matrix deposition, as evidenced by
      the irregular alignment of immature collagen fibers. Despite the presence of
      matrix abnormalities, MMP-9-null wounds displayed normal tensile strength.
      Ultrastructural analysis of wounds revealed the presence of large collagen
      fibrils, some with irregular shape. Keratinocyte proliferation, inflammation, and
      angiogenesis were found to be normal in MMP-9-null wounds. In addition, VEGF
      levels were similar in control and MMP-9-null wound extracts. To investigate the
      importance of MMP-9 in wound reepithelialization we tested human and murine
      keratinocytes in a wound migration assay and found that antibody-based blockade
      of MMP-9 function or MMP-9 deficiency retarded migration. Collectively, our
      observations reveal defective healing in MMP-9-null mice and suggest that MMP-9
      is required for normal progression of wound closure.

PMID- 19379669
TI  - Epilysin (MMP-28) is deposited to the basolateral extracellular matrix of
      epithelial cells.
AB  - Epilysin (MMP-28) is a conserved member of the matrix metalloproteinase (MMP)
      family. It is expressed in various normal tissues, and induced in wounds and in
      developing and regenerating nerves. Epilysin induces TGF-beta mediated epithelial
      to mesenchymal transition, but its other functions are largely unknown. We have
      characterized the localization of both catalytically active and mutated inactive,
      overexpressed epilysin in established epithelial cell lines. We found that
      epilysin was localized abundantly to the basolateral side of the cells and
      associated with the extracellular matrix (ECM) as verified by immunoblotting and
      confocal microscopy. Overexpression of epilysin in MDCK cells resulted in a
      drastic reduction of basolateral ECM, as observed by the disappearance of
      collagen type IV, laminin and fibronectin. Cultivation of epilysin expressing
      MDCK cells in defined serum free medium resulted in the restoration of these
      proteins to the ECM. The levels of fibronectin and collagen IV were, however,
      reduced in epilysin expressing cells under the serum free conditions, and
      degradation fragments of collagen IV were detected supporting the activation of
      proteolysis by epilysin. Epilysin was observed in its unprocessed 50 kDa active
      form in the ECM of MDCK cells under serum free conditions whereas in cells
      cultured in serum containing it was processed to the 48 kDa form. Current results
      indicate that epilysin associates with the basolateral ECM of cultured epithelial
      cells, where it plausibly plays a role in the regulation of matrix composition
      and turnover.

PMID- 19379681
TI  - The BAR domain superfamily: membrane-molding macromolecules.
AB  - Membrane-shaping proteins of the BAR domain superfamily are determinants of
      organelle biogenesis, membrane trafficking, cell division, and cell migration. An
      upsurge of research now reveals new principles of BAR domain-mediated membrane
      remodeling, enhancing our understanding of membrane curvature-mediated
      information processing.

PMID- 19379682
TI  - Altered GLUT1 substrate selectivity in human erythropoiesis?

PMID- 19379684
TI  - Fallen immortals.
AB  - The memory of somatic cell gene expression is reset in the germline in a process
      that is accompanied by dramatic changes in chromatin modifications. In this
      issue, Katz et al. (2009) show that the histone demethylase Lsd1/Spr-5 may
      participate in this resetting process in the worm, thereby preventing a decline
      in germ cell epigenetic stability and viability over ensuing generations.

PMID- 19379685
TI  - The nucleus inside out--through a rod darkly.
AB  - In the nuclei of eukaryotic cells, euchromatin is located at the center, whereas
      heterochromatin is found at the periphery and is interspersed in the nucleoplasm.
      Solovei et al. (2009) now reveal that this normal pattern is reversed in the
      retinal rod cells of mice. This inversion might serve to maximize light
      transmission to photoreceptors in nocturnal mammals.

PMID- 19379686
TI  - Neurite extension: starting at the finish line.
AB  - The outgrowth of axons and dendrites from neuronal cell bodies to their
      appropriate targets is the canonical means of creating new processes. Heiman and
      Shaham (2009) now show that neuronal processes can also be made by anchoring
      dendrite tips at their target locations while the cell body pulls away, a process
      termed retrograde extension.

PMID- 19379687
TI  - Ubiquitin connects with planar cell polarity.
AB  - Planar cell polarity (PCP) regulates the orientation of cells in epithelia and of
      mesenchymal cells during gastrulation. In this issue, Narimatsu et al. (2009)
      report that the Smurf E3 ubiquitin ligases are required for localized protein
      degradation of a core PCP factor to generate cellular asymmetry.

PMID- 19379688
TI  - DNA replication reaches the breaking point.
AB  - DNA strand breaks that result in stalled or damaged replication forks can be
      detrimental to the DNA replication process. In this issue, Doksani et al. (2009)
      examine the impact of a single double-stranded DNA break on replication in the
      budding yeast, Saccharomyces cerevisiae.

PMID- 19379689
TI  - VMA21 deficiency: a case of myocyte indigestion.
AB  - The Vma21p protein in yeast is an essential assembly chaperone for the vacuolar
      ATPase, the major proton pump of cellular membranes. In this issue, Ramachandran
      et al. (2009) report that mutations in the gene encoding the human homolog VMA21
      cause the disease X-linked myopathy with excessive autophagy through an
      unexpected mechanism.

PMID- 19379691
TI  - VMA21 deficiency causes an autophagic myopathy by compromising V-ATPase activity
      and lysosomal acidification.
AB  - X-linked myopathy with excessive autophagy (XMEA) is a childhood-onset disease
      characterized by progressive vacuolation and atrophy of skeletal muscle. We show
      that XMEA is caused by hypomorphic alleles of the VMA21 gene, that VMA21 is the
      diverged human ortholog of the yeast Vma21p protein, and that like Vma21p it is
      an essential assembly chaperone of the V-ATPase, the principal mammalian proton
      pump complex. Decreased VMA21 raises lysosomal pH, which reduces lysosomal
      degradative ability and blocks autophagy. This reduces cellular free amino acids,
      which upregulates the mTOR pathway and mTOR-dependent macroautophagy, resulting
      in proliferation of large and ineffective autolysosomes that engulf sections of
      cytoplasm, merge together, and vacuolate the cell. Our results uncover
      macroautophagic overcompensation leading to cell vacuolation and tissue atrophy
      as a mechanism of disease.

PMID- 19379690
TI  - The canonical Notch signaling pathway: unfolding the activation mechanism.
AB  - Notch signaling regulates many aspects of metazoan development and tissue
      renewal. Accordingly, the misregulation or loss of Notch signaling underlies a
      wide range of human disorders, from developmental syndromes to adult-onset
      diseases and cancer. Notch signaling is remarkably robust in most tissues even
      though each Notch molecule is irreversibly activated by proteolysis and signals
      only once without amplification by secondary messenger cascades. In this Review,
      we highlight recent studies in Notch signaling that reveal new molecular details
      about the regulation of ligand-mediated receptor activation, receptor
      proteolysis, and target selection.

PMID- 19379692
TI  - Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5'
      transcribed regions.
AB  - Cotranscriptional histone methylations by Set1 and Set2 have been shown to affect
      histone acetylation at promoters and 3' regions of genes, respectively. While
      histone H3K4 trimethylation (H3K4me3) is thought to promote nucleosome
      acetylation and remodeling near promoters, we show here that H3K4 dimethylation
      (H3K4me2) by Set1 leads to reduced histone acetylation levels near 5' ends of
      genes. H3K4me2 recruits the Set3 complex via the Set3 PHD finger, localizing the
      Hos2 and Hst1 subunits to deacetylate histones in 5' transcribed regions. Cells
      lacking the Set1-Set3 complex pathway are sensitive to mycophenolic acid and have
      reduced polymerase levels at a Set3 target gene, suggesting a positive role in
      transcription. We propose that Set1 establishes two distinct chromatin zones on
      genes: H3K4me3 leads to high levels of acetylation and low nucleosome density at
      promoters, while H3K4me2 just downstream recruits the Set3 complex to suppress
      nucleosome acetylation and remodeling.

PMID- 19379693
TI  - A microRNA imparts robustness against environmental fluctuation during
      development.
AB  - The microRNA miR-7 is perfectly conserved from annelids to humans, and yet some
      of the genes that it regulates in Drosophila are not regulated in mammals. We
      have explored the role of lineage restricted targets, using Drosophila, in order
      to better understand the evolutionary significance of microRNA-target
      relationships. From studies of two well characterized developmental regulatory
      networks, we find that miR-7 functions in several interlocking feedback and
      feedforward loops, and propose that its role in these networks is to buffer them
      against perturbation. To directly demonstrate this function for miR-7, we
      subjected the networks to temperature fluctuation and found that miR-7 is
      essential for the maintenance of regulatory stability under conditions of
      environmental flux. We suggest that some conserved microRNAs like miR-7 may enter
      into novel genetic relationships to buffer developmental programs against
      variation and impart robustness to diverse regulatory networks.

PMID- 19379694
TI  - Diversification of a Salmonella virulence protein function by ubiquitin-dependent
      differential localization.
AB  - Many bacterial pathogens and symbionts utilize type III secretion systems to
      deliver bacterial effector proteins into host cells. These effector proteins have
      the capacity to modulate a large variety of cellular functions in a highly
      regulated manner. Here, we report that the phosphoinositide phosphatase SopB, a
      Salmonella Typhimurium type III secreted effector protein, diversifies its
      function by localizing to different cellular compartments in a ubiquitin
      dependent manner. We show that SopB utilizes the same enzymatic activity to
      modulate actin-mediated bacterial internalization and Akt activation at the
      plasma membrane and vesicular trafficking and intracellular bacterial replication
      at the phagosome. Thus, by exploiting the host cellular machinery, Salmonella
      Typhimurium has evolved the capacity to broaden the functional repertoire of a
      virulence factor to maximize its ability to modulate cellular functions.

PMID- 19379695
TI  - Regulation of planar cell polarity by Smurf ubiquitin ligases.
AB  - Planar cell polarity (PCP) is critical for morphogenesis in metazoans. PCP in
      vertebrates regulates stereocilia alignment in neurosensory cells of the cochlea
      and closure of the neural tube through convergence and extension movements (CE).
      Noncanonical Wnt morphogens regulate PCP and CE in vertebrates, but the molecular
      mechanisms remain unclear. Smurfs are ubiquitin ligases that regulate signaling,
      cell polarity and motility through spatiotemporally restricted ubiquitination of
      diverse substrates. Here, we report an unexpected role for Smurfs in controlling
      PCP and CE. Mice mutant for Smurf1 and Smurf2 display PCP defects in the cochlea
      and CE defects that include a failure to close the neural tube. Further, we show
      that Smurfs engage in a noncanonical Wnt signaling pathway that targets the core
      PCP protein Prickle1 for ubiquitin-mediated degradation. Our work thus uncovers
      ubiquitin ligases in a mechanistic link between noncanonical Wnt signaling and
      PCP/CE.

PMID- 19379696
TI  - A C. elegans LSD1 demethylase contributes to germline immortality by
      reprogramming epigenetic memory.
AB  - Epigenetic information undergoes extensive reprogramming in the germline between
      generations. This reprogramming may be essential to establish a developmental
      ground state in the zygote. We show that mutants in spr-5, the Caenorhabditis
      elegans ortholog of the H3K4me2 demethylase LSD1/KDM1, exhibit progressive
      sterility over many generations. This sterility correlates with the misregulation
      of spermatogenesis-expressed genes and transgenerational accumulation of the
      histone modification dimethylation of histone H3 on lysine 4 (H3K4me2). This
      suggests that H3K4me2 can serve as a stable epigenetic memory, and that erasure
      of H3K4me2 by LSD/KDM1 in the germline prevents the inappropriate transmission of
      this epigenetic memory from one generation to the next. Thus, our results provide
      direct mechanistic insights into the processes that are required for epigenetic
      reprogramming between generations.

PMID- 19379697
TI  - A general O-glycosylation system important to the physiology of a major human
      intestinal symbiont.
AB  - The Bacteroides are a numerically dominant genus of the human intestinal
      microbiota. These organisms harbor a rare bacterial pathway for incorporation of
      exogenous fucose into capsular polysaccharides and glycoproteins. The infrequency
      of glycoprotein synthesis by bacteria prompted a more detailed analysis of this
      process. Here, we demonstrate that Bacteroides fragilis has a general O
      glycosylation system. The proteins targeted for glycosylation include those
      predicted to be involved in protein folding, protein-protein interactions,
      peptide degradation as well as surface lipoproteins. Protein glycosylation is
      central to the physiology of B. fragilis and is necessary for the organism to
      competitively colonize the mammalian intestine. We provide evidence that general
      O-glycosylation systems are conserved among intestinal Bacteroides species and
      likely contribute to the predominance of Bacteroides in the human intestine.

PMID- 19379698
TI  - Platelet matrix metalloprotease-1 mediates thrombogenesis by activating PAR1 at a
      cryptic ligand site.
AB  - Matrix metalloproteases (MMPs) play important roles in normal and pathological
      remodeling processes including atherothrombotic disease, inflammation,
      angiogenesis, and cancer. MMPs have been viewed as matrix-degrading enzymes, but
      recent studies have shown that they possess direct signaling capabilities.
      Platelets harbor several MMPs that modulate hemostatic function and platelet
      survival; however their mode of action remains unknown. We show that platelet MMP
      1 activates protease-activated receptor-1 (PAR1) on the surface of platelets.
      Exposure of platelets to fibrillar collagen converts the surface-bound proMMP-1
      zymogen to active MMP-1, which promotes aggregation through PAR1. Unexpectedly,
      MMP-1 cleaves PAR1 at a distinct site that strongly activates Rho-GTP pathways,
      cell shape change and motility, and MAPK signaling. Blockade of MMP1-PAR1
      curtails thrombogenesis under arterial flow conditions and inhibits thrombosis in
      animals. These studies provide a link between matrix-dependent activation of
      metalloproteases and platelet-G protein signaling and identify MMP1-PAR1 as a
      potential target for the prevention of arterial thrombosis.

PMID- 19379699
TI  - Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian
      evolution.
AB  - We show that the nuclear architecture of rod photoreceptor cells differs
      fundamentally in nocturnal and diurnal mammals. The rods of diurnal retinas
      possess the conventional architecture found in nearly all eukaryotic cells, with
      most heterochromatin situated at the nuclear periphery and euchromatin residing
      toward the nuclear interior. The rods of nocturnal retinas have a unique inverted
      pattern, where heterochromatin localizes in the nuclear center, whereas
      euchromatin, as well as nascent transcripts and splicing machinery, line the
      nuclear border. The inverted pattern forms by remodeling of the conventional one
      during terminal differentiation of rods. The inverted rod nuclei act as
      collecting lenses, and computer simulations indicate that columns of such nuclei
      channel light efficiently toward the light-sensing rod outer segments. Comparison
      of the two patterns suggests that the conventional architecture prevails in
      eukaryotic nuclei because it results in more flexible chromosome arrangements,
      facilitating positional regulation of nuclear functions.

PMID- 19379700
TI  - A functional screen to identify novel effectors of hematopoietic stem cell
      activity.
AB  - Despite tremendous progress made toward the identification of the molecular
      circuitry that governs cell fate in embryonic stem cells, genes controlling this
      process in the adult hematopoietic stem cell have proven to be more difficult to
      unmask. We now report the results of a novel gain-of-function screening approach,
      which identified a series of 18 nuclear factors that affect hematopoietic stem
      cell activity. Overexpression of ten of these factors resulted in an increased
      repopulating activity compared to unmanipulated cells. Interestingly, at least
      four of the 18 factors, Fos, Tcfec, Hmgb1, and Sfpi1, show non-cell-autonomous
      functions. The utilization of this screening method together with the creation of
      a database enriched for potential determinants of hematopoietic stem cell self
      renewal will serve as a resource to uncover regulatory networks in these cells.

PMID- 19379701
TI  - SnapShot: endocytic trafficking.

PMID- 19379702
TI  - In vitro analysis of cell metabolism using a long-decay pH-sensitive lanthanide
      probe and extracellular acidification assay.
AB  - Metabolic perturbations play a critical role in a variety of disease states and
      toxicities. Therefore, knowledge of the interplay between the two main cellular
      ATP generating pathways, glycolysis and oxidative phosphorylation, is
      particularly informative when examining such perturbations. Here we describe a
      new fluorescence-based screening assay for the assessment of glycolytic flux and
      demonstrate the value of such analysis in assessing the cellular "energy budget."
      The assay employs a long-decay pH-sensitive lanthanide probe to monitor
      extracellular acidification (ECA) in standard 96- or 384-well plates on a time
      resolved fluorescence plate reader. The simple mix-and-measure procedure and
      fluorescence lifetime-based pH sensing allow the use of standard adherent cell
      culture techniques, providing high sample throughput and excellent assay
      performance. The assay also facilitates multiplexed or parallel analysis with
      existing oxygen consumption and ATP assays, thereby providing a detailed
      multiparametric assessment of cell metabolism. Data on cellular CO(2) production
      can also be obtained by comparing sealed and unsealed samples. The utility of the
      approach in assessing perturbed cell metabolism is demonstrated using a panel of
      metabolic effectors with known mechanisms of action. More complex metabolic
      stimuli, such as G protein-coupled receptor (GPCR) activation and perturbed ion
      homeostasis, are also examined.

PMID- 19379703
TI  - Preparation of genome-wide DNA fragment libraries using bisulfite in
      polyacrylamide gel electrophoresis slices with formamide denaturation and quality
      control for massively parallel sequencing by oligonucleotide ligation and
      detection.
AB  - Bisulfite sequencing is widely used for analysis of DNA methylation status (i.e.,
      5-methylcytosine [5mC] vs. cytosine [C]) in CpG-rich or other loci in genomic DNA
      (gDNA). Such methods typically involve reaction of gDNA with bisulfite followed
      by polymerase chain reaction (PCR) amplification of specific regions of interest
      that, overall, converts C-->T (thymine) and 5mC-->C and then capillary sequencing
      to measure C versus T composition at CpG sites. Massively parallel sequencing by
      oligonucleotide ligation and detection (SOLiD) has recently enabled relatively
      low-cost whole genome sequencing, and it would be highly desirable to apply such
      massively parallel sequencing to bisulfite-converted whole genomes to determine
      DNA methylation status of an entire genome, which has heretofore not been
      reported. As an initial step toward achieving this goal, we have extended our
      ongoing interest in improving bisulfite conversion sample preparation to include
      a human genome-wide fragment library for SOliD. The current article features
      novel use of formamide denaturant during bisulfite conversion of a suitably
      constructed library directly in a band slice from polyacryamide gel
      electrophoresis (PAGE). To validate this new protocol for 5mC-protected fragment
      library conversion, which we refer to as Bis-PAGE, capillary-based size analysis
      and Sanger sequencing were carried out for individual amplicons derived from
      single-molecule PCR (smPCR) of randomly selected library fragments.
      smPCR/Capillary Sanger sequencing of approximately 200 amplicons unambiguously
      demonstrated greater than 99% C-->T conversion. All of these approximately 200
      Sanger sequences were analyzed with a previously published web-accessible
      bioinformatics tool (methBLAST) for mapping to human chromosomes, the results of
      which indicated random distribution of analyzed fragments across all chromosomes.
      Although these particular Bis-PAGE conversion and quality control methods were
      exemplified in the context of a fragment library for SOLiD, the concepts can be
      generalized to include other genome-wide library constructions intended for DNA
      methylation analysis by alternative high-throughput or massively parallelized
      methods that are currently available.

PMID- 19379704
TI  - Evaluation of a biosensor immunoassay for simultaneous characterization of
      isotype and binding region of human anti-tocilizumab antibodies with control by
      surrogate standards.
AB  - This article describes the simultaneous Biacore analysis of human anti-human
      antibodies (HAHAs) with respect to the binding region and the isotype by a
      combination of 11 single measurements per sample. The multiplexing single assay
      setup made efficient use of the four parallel flow cells on one biosensor chip by
      immobilization of full-length antibody and its constant (Fc) and antigen binding
      (Fab) fragments for differential binding analysis of anti-drug antibodies (ADAs).
      Thereby, a complete time-specific immunogenicity profile (intensity, isotype,
      specificity, and kinetics) of a patient could be obtained by assessing the
      response patterns of serially collected samples analyzed in a single measurement
      run. The use of functionally active standard conjugates allowed control of the
      assay performance throughout the whole procedure. The positive control standard
      conjugates mimicking polyclonal human ADAs of different isotypes were obtained by
      conjugating polyclonal rabbit antibodies against the therapeutic antibody to
      human immunoglobulin (Ig) M, IgG, or IgE. In this article, the qualification of
      the assay is demonstrated and the application of the methodology to six
      representative rheumatoid arthritis patients treated with the therapeutic
      humanized IgG1 antibody tocilizumab (anti-IL-6R) is shown to illustrate the
      versatility of the assay. The presented method allows one to differentiate
      specific ADAs from drug-unspecific responses (e.g., rheumatoid factors). In
      addition, the method can be used to discriminate between isotype responses of the
      IgG, IgM, and IgE types and, thereby, allows one to describe the time course of
      specific ADA formation and its disappearance on the single patient level.

PMID- 19379705
TI  - Analysis of 3-(acetylamino)-6-aminoacridine-derivatized oligosaccharides from
      recombinant monoclonal antibodies by liquid chromatography-mass spectrometry.
AB  - Glycosylation has been established as playing a pivotal role in various aspects
      of recombinant monoclonal antibodies (MAbs), ranging from pharmacokinetics to
      enhancement of effector function. Consequently, characterization of these
      oligosaccharides is of great importance and requires sensitive analytical
      techniques. Here we present a method for the rapid elucidation of 3-(acetylamino)
      6-aminoacridine-labeled N-glycans present on MAbs using liquid chromatography
      mass spectrometry. The technique uses the benefits of ultra-performance liquid
      chromatography systems in conjunction with small-particle-size amide columns
      capable of generating a fluorescence glycan profile of a MAb in 30 min, reducing
      the current run time by a factor of 6. The method is also compatible with online
      electrospray mass spectrometry, permitting the identification of glycans present.
      Overall, this strategy allows the confident determination of N-glycans present on
      recombinant MAbs in a significantly reduced amount of time.

PMID- 19379706
TI  - A three-phase liquid chromatographic method for delta13C analysis of amino acids
      from biological protein hydrolysates using liquid chromatography-isotope ratio
      mass spectrometry.
AB  - We report a three-phase chromatographic method for the separation and analysis of
      delta(13)C values of underivatized amino acids from biological proteins (keratin,
      collagen, and casein) using liquid chromatography-isotope ratio mass spectrometry
      (LC-IRMS). Both precision and accuracy of delta(13)C values for standard amino
      acid mixtures over the range of approximately 8 to 1320 ng of carbon per amino
      acid on the column were assessed. The precision of delta(13)C values of amino
      acids was found to be better at higher concentrations, whereas accuracy improved
      at lower concentrations. The optimal performance for this method was achieved
      with between 80 and 660 ng of carbon of each amino acid on the column. At amino
      acid amounts lower than 20 ng of carbon on the column, precision and accuracy may
      become compromised. The application of this new three-phase chromatographic
      technique will allow the analysis of delta(13)C of amino acids to be carried out
      as a routine method and benefit fields of research such as biomedicine,
      forensics, ecology, nutrition, and palaeodiet reconstruction in archaeology.

PMID- 19379707
TI  - Effect of the ATPase inhibitor protein IF1 on H+ translocation in the
      mitochondrial ATP synthase complex.
AB  - The H(+) F(o)F(1)-ATP synthase complex of coupling membranes converts the proton
      motive force into rotatory mechanical energy to drive ATP synthesis. The F(1)
      moiety of the complex protrudes at the inner side of the membrane, the F(o)
      sector spans the membrane reaching the outer side. The IF(1) component of the
      mitochondrial complex is a basic 10 kDa protein, which inhibits the F(o)F(1)-ATP
      hydrolase activity. The mitochondrial matrix pH is the critical factor for the
      inhibitory binding of the central segment of IF(1) (residue 42-58) to the F(1)
      alpha/beta subunits. We have analyzed the effect of native purified IF(1) the
      IF(1)-(42-58) synthetic peptide and its mutants on proton conduction, driven by
      ATP hydrolysis or by [K(+)] gradients, in bovine heart inside-out
      submitochondrial particles and in liposome-reconstituted F(o)F(1) complex. The
      results show that IF(1), and in particular its central 42-58 segment, displays
      different inhibitory affinity for proton conduction from the F(1) to the F(o)
      side and in the opposite direction. Cross-linking of IF(1) to F(1)-alpha/beta
      subunits inhibits the ATP-driven H(+) translocation but enhances H(+) conduction
      in the reverse direction. These observation are discussed in terms of the rotary
      mechanism of the F(o)F(1) complex.

PMID- 19379708
TI  - Microtubule-independent regulation of neurofilament interactions in vitro by
      neurofilament-bound ATPase activities.
AB  - Neurofilaments (NFs), the major neuronal intermediate filaments, form networks in
      vitro that mimic the axonal NF bundles. This report presents evidence for
      previously unknown regulation of the interactions between NFs by NF-associated
      ATPases. Two opposite effects on NF gelation in vitro occur at low and high ATP
      concentration. These findings support the hypothesis that NF bundles in situ are
      dynamic structures, and raise the possibility that ATP-hydrolyzing mechanoenzymes
      regulate their organization.

PMID- 19379709
TI  - Apical localization of PMCA2w/b is lipid raft-dependent.
AB  - Alternative splicing of the first intracellular loop differentially targets
      plasma membrane calcium ATPase (PMCA) isoform 2 to the apical or basolateral
      membrane in MDCK cells. To determine if the targeting is affected by lipid
      interactions, we stably expressed PMCA2w/b and PMCA2z/b in MDCK cells, and
      analyzed the PMCA distribution by confocal fluorescence microscopy and membrane
      fractionation. PMCA2w/b showed clear apical and lateral distribution, whereas
      PMCA2z/b was mainly localized to the basolateral membrane. A significant fraction
      of PMCA2w/b partitioned into low-density membranes associated with lipid rafts.
      Depletion of membrane cholesterol by methyl-beta-cyclodextrin resulted in reduced
      lipid raft association and a striking loss of PMCA2w/b from the apical membrane,
      whereas the lateral localization of PMCA2z/b remained unchanged. Our data
      indicate that alternative splicing differentially affects the lipid interactions
      of PMCA2w/b and PMCA2z/b and that the apical localization of PMCA2w/b is lipid
      raft-dependent and sensitive to cholesterol depletion.

PMID- 19379710
TI  - Molecular mechanisms controlling E-cadherin expression in breast cancer.
AB  - Disruption of cell-cell adhesion, which is essential for the maintenance of
      epithelial plasticity and is mediated by a class of proteins called cadherins, is
      an initial event in the progression of cancer. Cadherins are Ca(2+)-dependent
      transmembrane proteins that are associated with actin via other cytoplasmic
      proteins. Disruption of cell-cell adhesion during cancer progression is an
      important event during cancer initiation and metastasis. E-cadherin, one of the
      most widely studied tumor suppressors in breast cancer, belongs to a family of
      calcium-dependent cell adhesion molecules. Various signaling molecules and
      transcription factors regulate the expression of E-cadherin. Loss of E-cadherin
      has been reported to induce epithelial-mesenchymal transition in several cancers.
      This review highlights recent advances in defining the mechanisms that regulate E
      cadherin expression in breast cancer.

PMID- 19379711
TI  - Activating mutations of N-WASP alter Shigella pathogenesis.
AB  - The pathogenesis of Shigella requires binding to the host protein N-WASP. To
      examine the roles of structural conformation and phospho-regulation of N-WASP
      during Shigella pathogenesis, mutant N-WASP constructs predicted to result in a
      constitutively open conformation (L229P and L232P) or either a phospho-mimicking
      (Y253E) or phospho-disruptive (Y253F) structure were constructed. Pyrene actin
      assays demonstrated that the N-WASP L229P and L232P constructs are constitutively
      active. Despite the increase in actin polymerization seen in vitro, cell lines
      expressing N-WASP L229P and L232P supported shorter actin tails when infected
      with Shigella. Shigella actin tails were unchanged in cells expressing N-WASP
      phospho-regulation mutant proteins. Shigella invasion, intracellular, and
      intercellular motility were not altered in cells expressing N-WASP L229P or
      L232P. However, plaque numbers were increased in cells expressing N-WASP L229P
      and L232P. These data demonstrate that N-WASP structural conformation is an
      important regulator of Shigella pathogenesis in distinct segments of its
      lifecycle.

PMID- 19379712
TI  - The effect of hypusine modification on the intracellular localization of eIF5A.
AB  - Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein
      essential for eukaryotic cell proliferation and is the only protein containing
      hypusine, [N(epsilon)-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the
      post-translational synthesis of hypusine. eIF5A also undergoes an acetylation at
      specific Lys residue(s). In this study, we have investigated the effect of
      hypusine modification and acetylation on the subcellular localization of eIF5A.
      Immunocytochemical analyses showed differences in the distribution of non
      hypusinated eIF5A precursor and the hypusine-containing mature eIF5A. While the
      precursor is found in both cytoplasm and nucleus, the hypusinated eIF5A is
      primarily localized in cytoplasm. eIF5A mutant proteins, defective in hypusine
      modification (K50A, K50R) were localized in a similar manner to the eIF5A
      precursor, whereas hypusine-modified mutant proteins (K47A, K47R, K68A) were
      localized mainly in the cytoplasm. These findings provide strong evidence that
      the hypusine modification of eIF5A dictates its localization in the cytoplasmic
      compartment where it is required for protein synthesis.

PMID- 19379713
TI  - Ral GTPase interacts with the N-terminal in addition to the C-terminal region of
      PLC-delta1.
AB  - Previously, we have shown that RalA, a calmodulin (CaM)-binding protein, binds to
      the C2 region in the C-terminal of PLC-delta1, and increases its enzymatic
      activity. Since PLC-delta1 contains a CaM-like region in its N-terminus, we have
      investigated if RalA can also bind to the N-terminus of PLC-delta1. Therefore, we
      created a GST-PLC-delta1 construct consisting of the first 294 amino acids of PLC
      delta1 (GST-PLC-delta1(1-294)). In vitro binding experiments confirmed that PLC
      delta1(1-294) was capable of binding directly to RalA. W-7 coupled to
      polyacrylamide beads bound pure PLC-delta1, demonstrating that PLC-delta1
      contains a CaM-like region. Competition assays with W-7, peptides representing
      RalA and the newly identified RalB CaM-binding regions, or the IQ peptide from
      PLC-delta1 were able to inhibit RalA binding to PLC-delta1(1-294). This study
      demonstrates that there are two binding sites for RalA in PLC-delta1 and provides
      further insight into the role of Ral GTPase in the regulation of PLC-delta1
      function.

PMID- 19379714
TI  - Characterization of a PutCAX1 gene from Puccinellia tenuiflora that confers Ca2+
      and Ba2+ tolerance in yeast.
AB  - The gene for a novel cation/H+ antiporter from Puccinellia tenuiflora, PutCAX1,
      was cloned from a cDNA library. The PutCAX protein was localized in the vacuolar
      membrane using a GFP marker. Several yeast transformants were created using full
      length and truncated form of PutCAX1 and their growths in the presence of various
      cations (Mg2+, Ca2+, Mn2+, Ni2+, Cu2+, Zn2+, Se2+, and Ba2+) were analyzed.
      PutCAX1 expression was found to affect the response to Ca2+ and Ba2+ in yeast.
      The PutCAX1 and C-terminally truncated PutCAX1 (DeltaCPutCAX1) transformants grew
      in the presence of 70 mM Ca2+ as well as in the presence of 8 mM Ba2+. However,
      the DeltaCPutCAX1 transformant was able to grow in the presence of 20 mM Ba2+
      while the PutCAX1 transformant could not. On the other hand, expression of the N
      terminally truncated form and the N- and C-terminally truncated form failed to
      suppress the Ca2+ or Ba2+ sensitivity of yeast. These results suggest that
      PutCAX1 can complement the active Ca2+ transporters at some level and confer
      yeast Ba2+ tolerance, and that the N- and C-terminal regions of PutCAX1 play
      important roles in increasing the Ca2+ or Ba2+ tolerance of yeast.

PMID- 19379715
TI  - Modulation effect of filamentous phage on alpha-synuclein aggregation.
AB  - Conversion of soluble peptides and proteins into amyloid fibrils and/or
      intermediate oligomers is believed to be the central event in the pathogenesis of
      most human neurodegenerative diseases, including Parkinson's disease (PD). Here
      we describe the modulating effect of filamentous phages on aggregation of alpha
      synuclein (AS) in vitro and in a PD cellular model. Filamentous phages, well
      understood at both structural and genetic levels, have a nanotubular appearance,
      showing conformational similarities to amyloid fibrils. Since filamentous phages
      can infect only bacteria and have no tropism to mammalian cells, we utilized the
      f88 system to present a peptide containing a cyclic RGD (arg-gly-asp), which
      enabled phage internalization into the cells. Detection of intracellular AS
      oligomers, in differentiated SH-SY5Y cells, stably transfected with wild type AS
      gene, was performed using Western blot and ELISA measurements. Data presented
      here show reduced levels of AS soluble aggregates in phage treated cells compared
      to non-treated cells, suggesting new therapeutics for PD.

PMID- 19379716
TI  - Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell
      death in ischemic neuronal injury in PC12 cells.
AB  - High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is
      massively released into the extracellular space from neuronal cells after
      ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a
      semisynthetic second-generation tetracycline antibiotic which has recently been
      shown to be a promising neuroprotective agent. In this study, we found that
      minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated
      PC12 cells and triggered the activation of p38mitogen-activated protein kinase
      (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase
      (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in
      response to OGD. Furthermore, HMGB1 triggered cell death in a dose-dependent
      fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose
      dependent manner. In light of recent observations as well as the good safety
      profile of minocycline in humans, we propose that minocycline might play a potent
      neuroprotective role through the inhibition of HMGB1-induced neuronal cell death
      in cerebral infarction.

PMID- 19379717
TI  - A neurocomputational model of classical conditioning phenomena: a putative role
      for the hippocampal region in associative learning.
AB  - Some existing models of hippocampal function simulate performance in classical
      conditioning tasks using the error backpropagation algorithm to guide learning
      (Gluck, M.A., and Myers, C.E., (1993). Hippocampal mediation of stimulus
      representation: a computational theory. Hippocampus, 3(4), 491-516.). This
      algorithm is not biologically plausible because it requires information to be
      passed backward through layers of nodes and assumes that the environment provides
      information to the brain about what correct outputs should be. Here, we show that
      the same information-processing function proposed for the hippocampal region in
      the Gluck and Myers (1993) model can also be implemented in a network without
      using the backpropagation algorithm. Instead, our newer instantiation of the
      theory uses only (a) Hebbian learning methods which match more closely with
      synaptic and associative learning mechanisms ascribed to the hippocampal region
      and (b) a more plausible representation of input stimuli. We demonstrate here
      that this new more biologically plausible model is able to simulate various
      behavioral effects, including latent inhibition, acquired equivalence, sensory
      preconditioning, negative patterning, and context shift effects. In addition, the
      newer model is able to address some new phenomena including the effect of the
      number of training trials on blocking and overshadowing.

PMID- 19379718
TI  - Reversible inactivation of the auditory thalamus disrupts HPA axis habituation to
      repeated loud noise stress exposures.
AB  - Although habituation to stress is a widely observed adaptive mechanism in
      response to repeated homotypic challenge exposure, its brain location and
      mechanism of plasticity remains elusive. And while habituation-related plasticity
      has been suggested to take place in central limbic regions, recent evidence
      suggests that sensory sites may provide the underlying substrate for this
      function. For instance, several brainstem, midbrain, thalamic, and/or cortical
      auditory processing areas, among others, could support habituation-related
      plasticity to repeated loud noise exposures. In the present study, the auditory
      thalamus was tested for its putative role in habituation to repeated loud noise
      exposures, in rats. The auditory thalamus was inactivated reversibly by muscimol
      injections during repeated loud noise exposures to determine if brainstem or
      midbrain auditory nuclei would be sufficient to support habituation to this
      specific stressor, as measured during an additional and drug-free loud noise
      exposure test. Our results indicate that auditory thalamic inactivation by
      muscimol disrupts acute HPA axis response specifically to loud noise.
      Importantly, habituation to repeated loud noise exposures was also prevented by
      reversible auditory thalamic inactivation, suggesting that this form of
      plasticity is likely mediated at, or in targets of, the auditory thalamus.

PMID- 19379719
TI  - Effect of thyroid hormone T3 on myosin-Va expression in the central nervous
      system.
AB  - Thyroid hormones (THs) are essential for brain development, where they regulate
      gliogenesis, myelination, cell proliferation and protein synthesis.
      Hypothyroidism severely affects neuronal growth and establishment of synaptic
      connections. Triiodothyronine (T3), the biologically active form of TH, has a
      central function in these activities. So, Myosin-Va (Myo-Va), a molecular motor
      protein involved in vesicle and RNA transport, is a good candidate as a target
      for T3 regulation. Here, we analyzed Myo-Va expression in euthyroid and
      hypothyroid adult rat brains and synaptosomes. We observed a reduction of Myo-Va
      expression in cultured neural cells from newborn hypothyroid rat brain, while
      immunocytochemical experiments showed a punctate distribution of this protein in
      the cytoplasm of cells. Particularly, Myo-Va co-localized with microtubules in
      neurites, especially in their varicosities. Myo-Va immunostaining was stronger in
      astrocytes and neurons of controls when compared with hypothyroid brains. In
      addition, supplementation of astrocyte cultures with T3 led to increased
      expression of Myo-Va in cells from both euthyroid and hypothyroid animals,
      suggesting that T3 modulates Myo-Va expression in neural cells both in vivo and
      in vitro. We have further analyzed Myo-Va expression in U373 cells, a human
      glioblastoma line, and found the same punctate cytoplasmic protein localization.
      As in normal neural cells, this expression was also increased by T3, suggesting
      that the modulatory mechanism exerted by T3 over Myo-Va remains active on
      astrocyte tumor cells. These data, coupled with the observation that Myo-Va is
      severely affected in hypothyroidism, support the hypothesis that T3 activity
      regulates neural motor protein expression, taking Myo-Va as a model. As a
      consequence, reduced T3 activity could supposedly affect axonal transport and
      synaptic function, and could therefore explain disturbances seen in the
      hypothyroid brain.

PMID- 19379720
TI  - We don't need another hero--is there a role for ischemia biomarkers in patients
      with chest pain?

PMID- 19379721
TI  - Multi-locus interactions of vascular homeostasis genes in essential hypertension:
      a gender-based study.
AB  - BACKGROUND: Studies on genes of endothelial and vascular homeostasis are
      inadequate in females. METHODS: We investigated the role of 7 variants of ACE,
      AGT and NOS3 and their correlation with NO(x) levels and ACE activity in
      hypertension susceptibility in 910 case-controls of both genders. RESULTS:
      Prevalence of alleles D of ACE I/D; -6A of AGT -6G/A; -786C, 894T and 4a of NOS3 
      786T/C, 894G/T and 4b/4a polymorphisms was observed in patients (P< or =0.05).
      The 3 genotypes-combinations containing 6+5 wild-type alleles of AGT and NOS3
      were significantly less prevalent in patients (P< or =0.0003). The haplotypes
      235T/174T/-6A of AGT (P=4E-3) and -786T/894G/4a and -786C/894G/4a of NOS3 (P=2E
      3, P=0.011, respectively) were significantly more prevalent in patients. The AGT
      and NOS3 findings were similar in males. Genotypes-combinations with 6+5 wild
      type alleles of AGT correlated with higher NO(x) levels (P=0.03). The NOS3
      genotypes-combinations having 6 and 6+5 wild-type alleles correlated with
      decreased ACE activity (P=0.025, P=0.0015, respectively) and increased NO(x)
      levels (P=0.001, P=0.0001, respectively) in patients. In gene-gene interactions,
      ACE D allele associated with < or =4 wild-type alleles containing genotypes
      combinations of AGT and NOS3 in patients (P< or =0.04). CONCLUSION: Within gene
      and between genes interactions of variants influence ACE activity and NO(x)
      levels and associate with EH.

PMID- 19379722
TI  - Spinal mechanisms of antinociceptive action caused by guanosine in mice.
AB  - It is well known that adenine-based purines exert multiple effects on pain
      transmission. Recently, we have demonstrated that intracerebroventricular
      (i.c.v.) administered guanine-based purines are antinociceptive against chemical
      and thermal pain models in mice. The present study was designed to further
      investigate the antinociceptive effects of guanosine in mice. Animals received an
      intrathecal (i.t.) injection of vehicle (0.1 mN NaOH) or guanosine (10 to 400
      nmol). Measurements of cerebrospinal fluid (CSF) purine levels and spinal cord
      glutamate uptake were performed. Guanosine produced dose-dependent
      antinociceptive effects against tail-flick, hot-plate, intraplantar (i.pl.)
      capsaicin, and i.pl. glutamate tests. Additionally, i.t. guanosine produced
      significant inhibition of the biting behavior induced by i.t. injection of
      glutamate (175 nmol/site), AMPA (135 pmol/site), kainate (110 pmol/site), trans
      ACPD (50 nmol/site), and substance P (135 ng/site), with mean ID(50) values of
      140 (103-190), 136 (100-185), 162 (133-196), 266 (153-461) and 28 (3-292) nmol,
      respectively. However, guanosine failed to affect the nociception induced by NMDA
      (450 pmol/site) and capsaicin (30 ng/site). Intrathecal administration of
      guanosine (200 nmol) induced an approximately 120-fold increase on CSF guanosine
      levels. Guanosine prevented the increase on spinal cord glutamate uptake induced
      by i.pl. capsaicin. This study provides new evidence on the mechanism of action
      of guanosine presenting antinociceptive effects at spinal sites. This effect
      seems to be at least partially associated with modulation of glutamatergic
      pathways by guanosine.

PMID- 19379723
TI  - ASB16165, a phosphodiesterase 7A inhibitor, reduces cutaneous TNF-alpha level and
      ameliorates skin edema in phorbol ester 12-O-tetradecanoylphorbol-13-acetate
      induced skin inflammation model in mice.
AB  - Possible role of phosphodiesterase 7A (PDE7A) in skin inflammation was examined
      using ASB16165, a specific inhibitor for PDE7A. Epicutaneous application of
      phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ear resulted in
      induction of skin edema, and topical treatment with ASB16165 inhibited the
      induction of skin edema in a dose-dependent manner. The TPA challenge also
      increased the level of TNF-alpha at the application site, and the ASB16165
      treatment reduced the TNF-alpha level in the skin. In addition, ASB16165
      suppressed the production of TNF-alpha by human keratinocytes stimulated in vitro
      with TPA and calcium ionophore. Forskolin, an activator of adenylyl cyclase, as
      well as dibutyryl cAMP also showed inhibitory effect on the TNF-alpha production
      in the cells, suggesting involvement of cAMP in TNF-alpha generation. These
      results demonstrate that PDE7A might regulate TNF-alpha production in
      keratinocytes in a cAMP-dependent fashion. As immunostaining analysis revealed
      that PDE7A is expressed in the epidermis and TNF-alpha is known to contribute to
      the TPA-induced edema, it is possible that the inhibitory effect of ASB16165 on
      skin edema in mouse TPA-induced dermatitis model is mediated by suppression of
      TNF-alpha production. This is the first report suggesting the association of
      PDE7A with the function of keratinocytes. ASB16165 will be useful as an agent for
      skin inflammation in which TNF-alpha plays a pathogenic role (e.g. psoriasis).

PMID- 19379724
TI  - Food restriction and streptozotocin differentially modify sensitivity to the
      hypothermic effects of direct- and indirect-acting serotonin receptor agonists in
      rats.
AB  - Food restriction and experimentally-induced diabetes (streptozotocin) can modify
      serotonin (5-HT) neurotransmission and sensitivity to drugs acting on 5-HT
      systems. This study examined the effects of food restriction and streptozotocin
      on the hypothermic effects of the 5-HT(1A) receptor agonist (+)-8-hydroxy-2
      (dipropylamino)tetralin hydrobromide (8-OH-DPAT), the 5-HT(2) receptor agonist
      (+/-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (DOM), the 5-HT releaser
      fenfluramine, and the selective 5-HT reuptake inhibitor (SSRI) fluoxetine. All
      four drugs significantly decreased body temperature in free feeding rats.
      Limiting rats to 10 g/day of food for 7 days decreased body weight and
      sensitivity to 8-OH-DPAT induced hypothermia, without affecting sensitivity to
      DOM, fenfluramine, or fluoxetine induced hypothermia. Subsequently, 7 days of
      free feeding restored body weight and sensitivity to 8-OH-DPAT. Sensitivity to
      all drugs was significantly decreased 7 days after 50 mg/kg streptozotocin;
      subsequently, 10 days of insulin replacement restored sensitivity to all drugs.
      These results extend to body temperature the observation that food restriction
      and experimentally-induced diabetes differentially modify sensitivity to drugs
      acting on 5-HT systems and they further suggest that the clinical response to
      therapeutic drugs acting on 5-HT systems might be impacted by nutritional and
      insulin status.

PMID- 19379725
TI  - Preventive effects of raloxifene, a selective estrogen receptor modulator, on
      monocrotaline-induced pulmonary hypertension in intact and ovariectomized female
      rats.
AB  - We investigated whether the chronic treatment with raloxifene, a selective
      estrogen receptor modulator, prevents the development of monocrotaline-induced
      pulmonary hypertension in ovary-intact and ovariectomized female rats. Four weeks
      after a single subcutaneous injection of monocrotaline (60 mg/kg), right
      ventricular systolic pressure, right ventricle-to-left ventricle plus septal
      weight ratio, pulmonary arterial medial thickening and endothelin-1 levels in
      right ventricular tissue increased significantly in both female rats, compared
      with saline-treated control rats. These monocrotaline-induced alterations were
      much greater in ovariectomized rats than the changes in intact females. Daily
      oral administration of raloxifene (10 mg/kg/day for 4 weeks) significantly
      attenuated the increase in right ventricular systolic pressure to the same levels
      in both groups of animals, but raloxifene suppressed the increases in right
      ventricle-to-left ventricle plus septal weight ratio and pulmonary arterial
      medial thickness more efficiently in ovariectomized females than the case with
      intact females. In addition, raloxifene completely suppressed the increase in
      right ventricular endothelin-1 levels in ovariectomized rats, but not in intact
      females. These data suggest that chronic treatment with raloxifene effectively
      prevents the development of monocrotaline-induced pulmonary hypertension in
      ovariectomized female rats than in intact females, at least in part, by
      suppressing right ventricular endothelin-1 overproduction.

PMID- 19379726
TI  - Pyrrolidine dithiocarbamate, a NF-kappaB inhibitor, upregulates MMP-1 and MMP-13
      in IL-1beta-stimulated rheumatoid arthritis fibroblast-like synoviocytes.
AB  - Activated NF-kappaB plays an important role in the expression of matrix
      metalloproteinase (MMP)-1 and MMP-13 in rheumatoid arthritis and osteoarthritis.
      The objective of this study was to determine the effects of the NF-kappaB
      inhibitor pyrrolidine dithiocarbamate (PDTC) on the expression of MMPs in IL
      1beta-stimulated fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis
      patients. FLSs were treated with IL-1beta (10 ng/ml) for 24 h in the presence or
      absence of PDTC. The level of MMP-1 and MMP-13 increased in response to PDTC in
      time- and dose-dependent manners in IL-1beta-stimulated FLSs; the expressions of
      IL-6 and vascular endothelial growth factor (VEGF) decreased in a PDTC
      concentration-dependent manner. However, PDTC-mediated repression of IL-6 and
      VEGF expression was not observed in TNF-alpha-stimulated rheumatoid arthritis
      FLSs. In contrast, other NF-kappaB inhibitors, such as fenofibrate, N
      acetylcysteine and MG132, decreased MMP expression in IL-1beta-stimulated FLSs.
      The stimulatory effect of PDTC on MMP expression was not mimicked by specific
      inhibitors of the mitogen-activated protein kinase (MAPK) signaling pathway.
      Treatments with 100 muM PDTC did not inhibit the phosphorylation of p-ERK1/2, p
      P38, and p-JNK, or the transnuclear migration of NF-kappaB through degradation of
      IkappaB-alpha in IL-1beta-stimulated FLSs. These results suggest that the
      increase of MMP expression may occur in a stimuli-specific manner or by an NF
      kappaB independent mechanism. Therefore, therapeutic NF-kappaB inhibitors should
      be thoroughly studied before their clinical use in treating rheumatoid arthritis,
      as undesirable genes may be upregulated through unknown mechanisms, possibly
      resulting in worse symptoms.

PMID- 19379727
TI  - DP7, a novel dihydropyridine multidrug resistance reverter, shows only weak
      inhibitory activity on human CYP3A enzyme(s).
AB  - The aim of this study was to investigate the effects of 3,5-dibenzoyl-4-(3
      phenoxy-phenyl)-1,4-dihydro-2,6-dimethylpyridine (DP7), a novel multidrug
      resistance (MDR) reverter, on cytochrome P450 (CYP)-activities by human and rat
      liver microsomes. Effects of DP7 were assessed with use of selective substrates,
      markers of CYP activities. With rat microsomes, ethoxyresorufin (ETR) was used as
      substrate for CYP1A1, penthoxyresorufin (PTR) for 2B, benzyloxyresorufin (BZR)
      for 1A1/2, 2B, 2C, 3A. CYP3A enzyme activities of rat (3A2) and human (3A4) liver
      microsomes, were assessed fluorimetrically using either 7-benzyloxy-quinoline
      (BQ) or [3-[3(3,4-difluorobenzyl)oxy]-5,5-dimethyl-4-[4-(methylsulfonyl)
      phenyl]furan-2-(5H)-one] (DFB). When rat microsomes were incubated with DP7,
      concentration-inhibition curves were obtained. DP7 inhibitions gave IC(50) values
      of 3.8 microM for PTR, 3.8 microM for ETR and 10.4 microM for BZR and were not
      competitive in nature; moreover, they were reversible. When BQ was used as
      substrate of rat microsomes, DP7 inhibited its oxidation with an IC(50) value of
      4.17 microM, while this oxidation was inhibited by only 25% at the highest DP7
      concentration used (75 microM) with human microsomes. On the contrary, when DFB
      was used as substrate, DP7 showed identical IC(50) values (34.67 microM) with
      microsomal preparations from either species. The moderate inhibition of CYP
      isoforms of rat liver microsomes and the weak inhibition of human CYP3A4 enzyme
      activity operated by DP7, suggest that DP7 in man should not give rise to
      important, unpredictable pharmacokinetic interactions. This conclusion supports
      the role of this compound as a lead for the development of novel MDR reverterting
      dihydropyridines of therapeutic interest.

PMID- 19379728
TI  - Inhibitory effect of nonsteroidal anti-inflammatory drugs on adenosine transport
      in vascular smooth muscle cells.
AB  - It is generally accepted that the clinical efficacy of nonsteroidal anti
      inflammatory drugs (NSAIDs) arises mainly from the inhibition of cyclooxygenase
      (COX). However, more evidence has suggested that certain pharmacological actions
      of NSAIDs may be mediated by COX-independent mechanisms. The present study
      investigated the effects of NSAIDs on adenosine uptake in human aortic smooth
      muscle cells (HASMCs). Among the NSAIDs tested (all at 100 microM), aspirin,
      ibuprofen and naproxen had no effect on [(3)H]adenosine uptake. Piroxicam
      inhibited [(3)H]adenosine uptake by 30%, while etodolac, indomethacin,
      ketoprofen, mefenamic acid and sulindac inhibited [(3)H]adenosine by 13-18%.
      Sulindac sulfide, an active metabolite of sulindac, inhibited [(3)H]adenosine
      uptake and [(3)H]nitrobenzylmercaptopurine ribonucleoside (NBMPR) binding of
      HASMCs with IC(50) values of 40.67+/-4.82 and 24.19+/-3.76 muM, respectively.
      Kinetic studies revealed that sulindac sulfide was a competitive inhibitor of
      adenosine uptake. Using the nucleoside-transporter-deficient PK15NTD cells that
      stably express equilibrative nucleoside transport (ENT) 1 and ENT2, it was found
      that the inhibitory effect of sulindac sulfide on ENT1 was greater than that on
      ENT2. Sulindac sulfide increased the extracellular adenosine level. In addition,
      it inhibited the proliferation of HASMCs and this anti-proliferative effect could
      be abolished by adenosine A(2B) receptor antagonist. Our results suggest that
      sulindac sulfide may exert pharmacological effects through the inhibition of
      adenosine uptake, which modulates the availability of adenosine in the vicinity
      of adenosine receptors.

PMID- 19379729
TI  - Morroniside protects human neuroblastoma SH-SY5Y cells against hydrogen peroxide
      induced cytotoxicity.
AB  - Oxidative stress-induced cell damage has been implicated in a variety of
      neurodegenerative disorders. Morroniside, an iridorid glycoside isolated from
      Cornus officinalis Sieb. Et Zucc., has shown potent antioxidant properties. The
      present study investigated the protective actions of morroniside against the
      cytotoxicity produced by exposure to H(2)O(2) (300-500 microM) in SH-SY5Y cells.
      Intracellular accumulation of Ca(2+), and decreases in mitochondrial membrane
      potential (MMP) caused by added H(2)O(2) were reduced by morroniside. Incubation
      of cells with H(2)O(2) caused a marked decrease in superoxide dismutase (SOD)
      activity; this decrease was significantly inhibited by morroniside. In addition,
      the percentage of cells undergoing H(2)O(2)-induced apoptosis was decreased, dose
      dependently, in the presence of morroniside. These results suggest that
      morroniside has protective effects against oxidative stress-induced neurotoxic
      processes.

PMID- 19379730
TI  - Increased protein carbonylation of red blood cell membrane in diabetic
      retinopathy.
AB  - We investigated the protein carbonylation of red blood cell (RBC) membrane in
      type 2 diabetic patients and the potential implication of carbonyl/oxidative
      stress in reflecting disease severity. Sixty-four diabetic patients with or
      without retinopathy of variable clinical severity (Groups DR and DM,
      respectively) and 20 healthy controls were included in the study. Protein
      carbonyls were determined in RBC membranes by immunoblotting. Compared to healthy
      volunteers, the RBC membranes of diabetic patients were characterized by
      significantly increased levels of carbonylated proteins. The carbonylation of
      Group DR was higher compared to that of Group DM. The subgroup of patients with
      proliferative retinopathy exhibited a trend towards a significant increase in
      protein carbonyls, compared to both free-of-retinopathy diabetic cases and non
      proliferative diabetic retinopathy cases. The correlation between the chemical
      modifications of the erythrocyte membrane proteins and the clinical severity of
      diabetic retinopathy suggests a potential utility of membrane carbonylation as a
      marker and risk factor in the development of retinopathy.

PMID- 19379731
TI  - PLC-gamma1 regulates fibronectin assembly and cell aggregation.
AB  - Phospholipase C-gamma1 (PLC-gamma1) mediates cell adhesion and migration through
      an undefined mechanism. Here, we examine the role of PLC-gamma1 in cell-matrix
      adhesion in a hanging drop assay of cell aggregation. Plcg1 Null (-/-) mouse
      embryonic fibroblasts formed aggregates that were larger and significantly more
      resistant to dissociation than cells in which PLC-gamma1 is re-expressed (Null+
      cells). Aggregate formation could be disrupted by inhibition of fibronectin
      interaction with integrins, indicating that fibronectin assembly may mediate
      aggregate formation. Fibronectin assembly was mediated by integrin alpha5beta1 in
      both cell lines, while assays measuring fibronectin assembly revealed increased
      assembly in the Null cells. Null and Null+ cells exhibited equivalent fibronectin
      mRNA levels and equivalent levels of fibronectin protein in pulse-labeling
      experiments. However, levels of secreted fibronectin in the conditioned medium
      were increased in Null cells. The data implicates a negative regulatory role for
      PLC-gamma1 in cell aggregation by controlling the secretion of fibronectin into
      the media and its assembly into fibrils.

PMID- 19379732
TI  - Topological studies of hSVCT1, the human sodium-dependent vitamin C transporter
      and the influence of N-glycosylation on its intracellular targeting.
AB  - The Na(+)-dependent transporters, hSVCT1 and hSVCT2, were assessed in COS-1 cells
      for their membrane topology. Antibodies to N- and C-termini of hSVCT1 and C
      terminus of hSVCT2 identified positive immunofluorescence only after
      permeabilisation, suggesting these regions are intracellular. PNGase F treatment
      confirmed that WT hSVCT1 (approximately 70-100 kDa) is glycosylated and site
      directed mutagenesis of the three putative N-glycosylation sites, Asn138, Asn144,
      Asn230, demonstrated that mutants N138Q and N144Q were glycosylated
      (approximately 68-90 kDa) with only 31-65% of WT l-ascorbic acid (AA) uptake
      while the glycosylation profile of N230Q remained unaltered (approximately 98% of
      WT activity). However, the N138Q/N144Q double mutant displayed barely detectable
      membrane expression at approximately 65 kDa, no apparent glycosylation and
      minimal AA uptake (<10%) with no discernible improvement in expression or
      activity when cultured at 28 degrees C or 37 degrees C. Marker protein
      immunocytochemistry with N138Q/N144Q identified intracellular aggregates with
      hSVCT1 localised at the nuclear membrane but absent at the plasma membrane thus
      implicating its role as a possible intracellular transporter and suggesting N
      glycosylation is required for hSVCT1 membrane targeting. Also, Lys242 on the same
      putative hydrophilic loop as Asn230 after biotinylation was inaccessible from the
      extracellular side when analysed by MALDI-TOF MS. A new hSVCT1 secondary
      structure model supporting these findings is proposed.

PMID- 19379733
TI  - Dehydroepiandrosterone protects human keratinocytes against apoptosis through
      membrane binding sites.
AB  - Although the epidermis is importantly affected by steroid hormones, little is
      known about the effects of dehydroepiandrosterone (DHEA) on human keratinocytes,
      in spite of its abundance in human serum. Here, we demonstrate for the first time
      a protective role of DHEA against apoptosis in keratinocytes, using non-cancerous
      immortalized human HaCaT cells. We show that DHEA transmits its signal via
      specific G protein-coupled, membrane binding sites and inhibits apoptosis,
      through prevention of mitochondrial disruption and altered balance of Bcl-2
      proteins. DHEA conjugated to the membrane impermeable molecule BSA, as well as
      DHEA-S, the most abundant form of DHEA in human serum exhibit similar anti
      apoptotic effect. Our data provide new insights in the treatment of the epidermis
      with steroid hormones in apoptosis-related conditions.

PMID- 19379734
TI  - Calcium-independent phospholipase A2 regulates retinal pigment epithelium
      proliferation and may be important in the pathogenesis of retinal diseases.
AB  - Calcium-independent phospholipase A2, group VIA (iPLA2-VIA) is involved in cell
      proliferation. This study aimed to evaluate the role of iPLA2-VIA in retinal
      pigment epithelium (RPE) cell proliferation and in retinal diseases involving RPE
      proliferation. A human RPE cell line (ARPE-19) was used to explore this role in
      vitro. Proliferating ARPE-19 cells had increased expression and activity of iPLA2
      VIA. iPLA2-VIA was found in the nuclei of proliferating ARPE-19 cells, whereas in
      confluent ARPE-19 cells, with limited proliferation, iPLA2-VIA was primarily
      found in the cytosol. Inhibition of iPLA2-VIA decreased the rate of
      proliferation, whereas over expression of iPLA2-VIA increased the rate of
      proliferation. Using an experimental porcine model of RPE proliferation we
      demonstrated significant nuclear upregulation of iPLA2-VIA in proliferating RPE
      cells in vivo. We furthermore evaluated the expression of iPLA2-VIA in
      proliferative vitreoretinopathy (PVR). PVR membranes revealed nuclear expression
      of iPLA2-VIA in the RPE cells which had migrated and participated in the
      formation of the membranes. Overall, the present results point to an important
      role of iPLA2-VIA in the regulation of RPE proliferation suggesting that iPLA2
      VIA may be considered as a possible pharmaceutical target in retinal diseases
      involving RPE proliferation and migration.

PMID- 19379735
TI  - Cell differentiation in the retina of an epibenthonic teleost, the Tench (Tinca
      tinca, Linneo 1758).
AB  - Here we present a detailed study of the major events in the retinal histogenesis
      in a freshwater epibenthonic fish species, the Tench (Tinca tinca, Linneo 1758)
      during embryonic, prolarval, larval, and juvenile stages, using classical
      histological and immunohistological methods, providing a complete neurochemical
      characterization of retinal cells. We find a morphologically undifferentiated
      retina during embryonic stages and even at the hatching stage (postnatal day 0,
      P0). However, the emergence of the different retinal layers occurs in the first
      postnatal day (P1). Proliferating PCNA-positive cells are found in the retina of
      all postnatal individuals included in the present study, located in the
      circumferential germinal zone (CGZ), and in sparse cells dispersed throughout the
      inner nuclear layer (INL) and the outer nuclear layer (ONL). All neurochemical
      markers used start to express between P0 and P2. Anti-opsin, -alpha-protein
      kinase C, -alpha-tyrosine hydroxylase, -glutamine synthetase antibodies stain
      selectively different subpopulations of photoreceptor, bipolar, amacrine, and
      Muller cells respectively. Parvalbumin immunoreactivity is detected in amacrine
      and displaced amacrine cells. Several subpopulations of calretinin-positive
      ganglion, amacrine, and bipolar cells are detected in tench retina. Islet1
      expression is confined to the nuclei of subpopulations of ganglion, amacrine,
      bipolar, and horizontal cells. All the maturational events described are first
      detected in the central retina and, as development progresses, they spread to the
      rest of the retina following a central-to-peripheral gradient. Therefore, tench
      postnatal retinal differentiation is a remarkable process not observed in the
      more common models of teleosts used in developmental biology.

PMID- 19379736
TI  - Distribution of Muller stem cells within the neural retina: evidence for the
      existence of a ciliary margin-like zone in the adult human eye.
AB  - Much interest has been generated by the identification of neural stem cells in
      the human neural retina and ciliary body. However, it is not clear whether stem
      cells identified in these ocular compartments are of the same origin or whether
      they ontogenically derive from different cell populations. This study examined
      the in situ anatomical distribution of these cells within the neural retina and
      ciliary body, as well as their ability to proliferate in response to EGF. Human
      retinae and ciliary body were examined for co-expression of Nestin, cellular
      retinaldehyde binding (CRALBP) or Vimentin, and the stem cell markers SOX2,
      CHX10, NOTCH1 and SHH. Retinal explants were cultured with epidermal growth
      factor (EGF) to assess retinal cell proliferation. Intense Nestin and CRALBP
      staining was observed in the neural retinal margin, where cells formed bundles of
      spindle cells (resembling glial cells) that lacked lamination and co-stained for
      SOX2, CHX10 and SHH. This staining differentiated the neural retina from the
      ciliary epithelium, which expressed SOX2, CHX10 and NOTCH1 but not Nestin or
      CRALBP. Nestin and CRALBP expression decreased towards the posterior retina,
      where it anatomically identified a population of Muller glia. All Vimentin
      positive Muller glia co-stained for SOX2, but only few Vimentin positive cells
      expressed Nestin and SOX2. Cells of the retinal margin and the inner nuclear
      layer (INL), where the soma of Muller glia predominate, re-entered the cell cycle
      upon retinal explant culture with EGF. Lack of lamination and abundance of Muller
      glia expressing stem cell markers in the marginal region of the adult human
      retina resemble the ciliary marginal zone (CMZ) of fish and amphibians. The
      findings that cells in this CM-like zone, as well in the inner nuclear layer
      proliferate in response to EGF suggest that the adult human retina has
      regenerative potential. Identification of factors that may promote retinal
      regeneration in the adult human eye would provide efficient treatments for
      retinal degenerative conditions for which treatments are not yet available.

PMID- 19379737
TI  - Nr2e3-directed transcriptional regulation of genes involved in photoreceptor
      development and cell-type specific phototransduction.
AB  - The retinal transcription factor Nr2e3 plays a key role in photoreceptor
      development and function. In this study we examine gene expression in the retina
      of Nr2e3(rd7/rd7) mutants with respect to wild-type control mice, to identify
      genes that are misregulated and hence potentially function in the Nr2e3
      transcriptional network. Quantitative candidate gene real time PCR and
      subtractive hybridization approaches were used to identify transcripts that were
      misregulated in Nr2e3(rd7/rd7) mice. Chromatin immunoprecipitation assays were
      then used to determine which of the misregulated transcripts were direct targets
      of NR2E3. We identified 24 potential targets of NR2E3. In the developing retina,
      NR2E3 targets transcription factors such as Ror1, Rorg, and the nuclear hormone
      receptors Nr1d1 and Nr2c1. In the mature retina NR2E3 targets several genes
      including the rod specific gene Gnb1 and cone specific genes blue opsin, and two
      of the cone transducin subunits, Gnat2 and Gnb3. In addition, we identified 5
      novel transcripts that are targeted by NR2E3. While mislocalization of proteins
      between rods and cones was not observed, we did observe diminished concentration
      of GNB1 protein in adult Nr2e3(rd7/rd7) retinas. These studies identified novel
      transcriptional pathways that are potentially targeted by Nr2e3 in the retina and
      specifically demonstrate a novel role for NR2E3 in regulating genes involved in
      phototransduction.

PMID- 19379738
TI  - Human iris pigment epithelial cells suppress T-cell activation via direct cell
      contact.
AB  - The purposes of the present study were to investigate whether cultured human iris
      pigment epithelial (hIPE) cells acquire the ability to modify T-cell activation,
      and if so, to identify the mechanism. Human IPE cells were prepared from patients
      who underwent glaucoma surgery, and were cultured in RPMI 1640 medium containing
      10% fetal calf serum for 4-7 days. Expression of MHC molecules and co-stimulatory
      molecules on cultured hIPE cells either unstimulated or stimulated with IFN-gamma
      was examined by FACS. In addition, peripheral blood T cells were incubated with
      cultured hIPE cells prepared from the same patients and anti-CD3 antibody in a
      transwell culture system, or in the presence of anti-PD-L1 and PD-L2 antibodies,
      and T cell proliferation was assessed by [3H]-thymidine incorporation. The hIPE
      cells inhibited anti-CD3-driven T-cell activation but the inhibition was
      diminished when tested in the transwell culture system, indicating that a contact
      dependent mechanism is important in the immunoregulatory roles of hIPE. Although
      cultured hIPE cells expressed Class I and PD-L1 but not Class II or PD-L2, all
      these molecules were observed on hIPE cells cultured in the presence of IFN
      gamma. Blocking antibodies against both PD-L1 and PD-L2 reduced the
      immunoregulatory activity of hIPE cells. Our data indicates that cultured hIPE
      cells inhibit T-cell activation by T-cell receptor ligation, which is mediated by
      cell-to-cell contact in part via the PD-L1 and PD-L2 pathways.

PMID- 19379739
TI  - Changes in the expression of Pax6 RNA transcripts in the retina during periods of
      altered ocular growth in chickens.
AB  - Genome-wide mapping studies have suggested a possible role for Pax6 in the
      development of myopia. We therefore investigated the expression of Pax6 RNA
      transcripts in the chicken retina during periods of increased ocular growth,
      induced by form-deprivation and negative lens-wear, and during periods of
      decreased ocular growth, induced by diffuser removal from previously form
      deprived eyes, and plus lens-wear. Levels of Pax6 RNA transcripts in the chicken
      retina were measured using semi-quantitative real-time RT-PCR, at times between 1
      h and 10 days after the fitting of diffusers or negative lenses, and at times
      between 1h and 3 days following the removal of diffusers from previously form
      deprived eyes, or the addition of plus lenses. Pax6 expression was unaffected
      during the initial 3 days of the response to form-deprivation or negative lens
      wear, when rapid rates of growth are well-established. Alterations in the
      expression of Pax6 RNA transcripts were only observed after 7-10 days of form
      deprivation (7 days, -15.7 +/- 5.3%; 10 days, -32.0 +/- 10.3%), with a similar
      response not seen during negative lens-wear, when eye growth also increases,
      suggesting that these alterations are specific to form-deprivation, rather to
      changes in the rate of eye growth. The late changes in Pax6 expression observed
      during form-deprivation were rapidly reversed after diffuser removal, with the
      levels of Pax6 RNA transcripts returning to those seen in control birds by 3 days
      (1 h, -27.8 +/- 4.7%; 1 day, -16.9 +/- 4.8%; 3 days + 1.0 +/- 8.6%). Analogous
      changes were not seen in response to positive lenses in which eye growth is also
      slowed. Overall, the findings of this study do not support a role for Pax6 in the
      modulation of ocular growth during visual manipulation.

PMID- 19379740
TI  - Increased sensitivity of myoblasts to oxidative stress in amyotrophic lateral
      sclerosis peripheral tissues.
AB  - We compared mitochondrial respiratory chain function, mitochondrial DNA (mtDNA)
      integrity, and oxidative stress levels in muscle, myoblasts, fibroblasts and
      cybrids, from 12 amyotrophic lateral sclerosis (ALS) patients with 28 control
      samples. Mitochondrial respiratory chain enzyme activities were normal in muscle,
      myoblast and fibroblast cultures from ALS patients, as were levels of mtDNA in
      muscle. Rearranged muscle mtDNA species were not detected by Southern blot
      hybridization in any of the samples and no difference was found in the number of
      deleted mtDNA species detected by long-range PCR. Platelet-derived cybrid studies
      confirmed the absence of a systemic mtDNA abnormality. Aconitase activity
      measurements did not indicate increased oxidative damage in muscle tissue, or in
      myoblasts or fibroblasts from ALS patients cultured under basal conditions. We
      did, however, find an increased sensitivity to oxidative stress in myoblasts from
      ALS patients exposed to paraquat. This altered sensitivity appears to be due to a
      nuclear rather than a mtDNA abnormality. Motor neurons have a large relative size
      and metabolic activity, and would be expected to be exposed to a greater degree
      of oxidative stress than most tissues throughout life. In addition, neurons are
      postmitotic cells, with poor regenerative potential. We do not have a ready
      method to study this in neural tissue of living patients, but the oxidative
      stress identified in myoblasts would translate into oxidative damage more readily
      in motor neurons than in other tissues.

PMID- 19379741
TI  - Activation of glucocorticoid receptors increases 5-HT2A receptor levels.
AB  - Major depression is associated with both dysregulation of the hypothalamic
      pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A
      receptor. However, how these phenomena are linked to each other, and whether a
      low 5-HT2A receptor level is a state or a trait marker of depression is unknown.
      In mice with altered glucocorticoid receptor (GR) expression we investigated 5
      HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin
      fibre density was analyzed by stereological quantification of serotonin
      transporter immunopositive fibers. To establish an effect of GR activation on 5
      HT2A levels, mature organotypic hippocampal cultures were exposed to
      corticosterone with or without GR antagonist mifepristone and mineralocorticoid
      receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal
      5-HT2A receptor protein levels were decreased (26.3 +/- 1.6%, p < 0.05) and
      frontal 5-HT2A receptor binding was decreased (20 +/- 15%, p < 0.01) as compared
      to wild-type mice. Conversely, in over-expressing GR mice hippocampal 5-HT2A
      receptor protein levels were increased (60.8 +/- 4.0%, p = 0.0001) and 5-HT2A
      receptor binding was increased in dorsal hippocampus (77 +/- 35%, p < 0.05) as
      compared to wild-type mice. No difference in serotonin fibre density was observed
      in the GR over-expressing mice, while the GR under-expressing mice showed lower
      serotonergic innervation in the frontal cortex area. An effect of GR activation
      on 5-HT2A receptor levels was further corroborated by the culture studies as long
      term exposure of 3 microM corticosterone to organotypic hippocampal cultures
      increased 5-HT2A receptor levels (p < 0.05). The corticosterone-induced 5-HT2A
      receptor up-regulation was blocked by addition of either spironolactone or
      mifepristone.

PMID- 19379742
TI  - Hydrolysis of the phosphoanhydride linkage of cyclic ADP-ribose by the Mn(2+)
      dependent ADP-ribose/CDP-alcohol pyrophosphatase.
AB  - Cyclic ADP-ribose (cADPR) metabolism in mammals is catalyzed by NAD
      glycohydrolases (NADases) that, besides forming ADP-ribose, form and hydrolyze
      the N(1)-glycosidic linkage of cADPR. Thus far, no cADPR phosphohydrolase was
      known. We tested rat ADP-ribose/CDP-alcohol pyrophosphatase (ADPRibase-Mn) and
      found that cADPR is an ADPRibase-Mn ligand and substrate. ADPRibase-Mn activity
      on cADPR was 65-fold less efficient than on ADP-ribose, the best substrate. This
      is similar to the ADP-ribose/cADPR formation ratio by NADases. The product of
      cADPR phosphohydrolysis by ADPRibase-Mn was N(1)-(5-phosphoribosyl)-AMP,
      suggesting a novel route for cADPR turnover.

PMID- 19379743
TI  - BS69 negatively regulates the canonical NF-kappaB activation induced by Epstein
      Barr virus-derived LMP1.
AB  - Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) activates NF-kappaB
      signaling pathways through the two C-terminal regions, CTAR1 and CTAR2. BS69 has
      previously been shown to be involved in LMP1-induced c-Jun N-terminal kinase
      activation through CTAR2 by interacting with tumor necrosis factor (TNFR)
      receptor-associated factor 6. In the present study, our manipulation of BS69
      expression clearly indicates that BS69 negatively regulates LMP1-mediated NF
      kappaB activation and up-regulates IL-6 mRNA expression and IkappaB degradation.
      Our immunoprecipitation experiments suggest that BS69 decreases complex formation
      between LMP1 and TNFR-associated death domain protein (TRADD).

PMID- 19379744
TI  - Next-generation sequencing approaches in genetic rodent model systems to study
      functional effects of human genetic variation.
AB  - Rapid advances in DNA sequencing improve existing techniques and enable new
      approaches in genetics and functional genomics, bringing about unprecedented
      coverage, resolution and sensitivity. Enhanced toolsets can facilitate the
      untangling of connections between genomic variation, environmental factors and
      phenotypic effects, providing novel opportunities, but may also pose challenges
      in data interpretation, especially in highly heterogeneous human populations.
      Laboratory rodent strains, however, offer a variety of tailored model systems
      with controlled genetic backgrounds, facilitating complex genotype/phenotype
      relationship studies. In this review we discuss the advent of massively parallel
      sequencing, its methodological advantage for molecular analysis in model
      organisms and the expectation of increased understanding of biologically relevant
      consequences of human genetic variation.

PMID- 19379745
TI  - Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and
      locomotive behavior.
AB  - Pathological modifications in the highly conserved and ubiquitously expressed
      heterogeneous ribonucleoprotein TDP-43 were recently associated to
      neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a late
      onset disorder that affects predominantly motoneurons [Neumann, M. et al. (2006)
      Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral
      sclerosis. Science 314, 130-133, Sreedharan, J. et al. (2008) TDP-43 mutations in
      familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672,
      Kabashi, E. et al. (2008) TARDBP mutations in individuals with sporadic and
      familial amyotrophic lateral sclerosis. Nat. Genet. 40, 572-574]. However, the
      function of TDP-43 in vivo is unknown and a possible direct role in
      neurodegeneration remains speculative. Here, we report that flies lacking
      Drosophila TDP-43 appeared externally normal but presented deficient locomotive
      behaviors, reduced life span and anatomical defects at the neuromuscular
      junctions. These phenotypes were rescued by expression of the human protein in a
      restricted group of neurons including motoneurons. Our results demonstrate the
      role of this protein in vivo and suggest an alternative explanation to ALS
      pathogenesis that may be more due to the lack of TDP 43 function than to the
      toxicity of the aggregates.

PMID- 19379746
TI  - From transcriptome analysis to immunogenomics: current status and future
      direction.
AB  - In 1994, we pioneered a complementary DNA (cDNA) sequencing project that aimed to
      predict the primary structures of unknown human proteins. Although our cDNA
      project was focused on the sequencing of large cDNAs, the following cDNA
      sequencing projects conducted by other groups have more extensively characterized
      mammalian transcriptome. In parallel, many groups have made a tremendous amount
      of effort to develop various resources for functional human genomics. In this
      context, to demonstrate the power of functional genomic approaches in practice,
      we have applied them for a comprehensive understanding of the immune system,
      which we term 'immunogenomics'. This mini-review first describes the historical
      background of our cDNA project and then provides perspectives on the present and
      future of immunogenomics based on our experiences.

PMID- 19379748
TI  - Next-generation stool DNA testing: expanding the scope.

PMID- 19379751
TI  - New insights into the mechanisms of pancreatitis.

PMID- 19379753
TI  - Transfection of Eimeria and Toxoplasma using heterologous regulatory sequences.
AB  - Eimeriatenella and Toxoplasmagondii are Apicomplexan protozoa and share many
      similarities in biology and genomics. While the latter parasites are easily
      cultured in vitro and genetically manipulated, many Eimeria species are difficult
      to grow in vitro. We hypothesised that molecular tools for the genetic
      manipulation of T. gondii could be applied to the study of Eimeria parasites.
      Here we show that three different promoter sequences originating from E. tenella
      could function effectively not only in other species of the Eimeria genus
      (histone H4) but also in T. gondii (histone H4, actin and tubulin). Similarly,
      promoters of the "housekeeping" gene (tubulin) and differentially regulated gene
      (surface antigen gene, sag1) of T. gondii were effective in driving the
      expression of the yellow fluorescent protein (YFP) maker gene in E. tenella. The
      transfection efficiency with heterologous regulatory sequences was similar to
      that with homologous promoters; while the promoter strength of heterologous
      vectors is slightly weaker than the homologous vectors in both E. tenella and T.
      gondii. The results suggest that 5' regulatory sequences are functionally
      conserved not only among the Eimeria species, but also between T. gondii and E.
      tenella, and that T. gondii could be used as a novel transfection check system
      for Eimeria-rooted vectors, accelerating the development of reverse genetics in
      Eimeria spp.

PMID- 19379754
TI  - Study on nonspecificity of an immuoassay using Eu-doped polystyrene nanoparticle
      labels.
AB  - Nanoparticle labels have been shown to improve the sensitivity of a sandwich
      immunoassay significantly. Further improvement in sensitivity is limited by
      nonspecific binding of the nanoparticle labels. Here, an experimental
      characterization of assay performance was carried out using clinically important
      analytes thyroid stimulating hormone and prostate-specific antigen. Particular
      attention was paid to characterization of nonspecific binding properties of
      nanoparticle labels. Therefore, different particle sizes and high affinity
      monoclonal antibodies (Mab) and their Fab and scFv recombinant antibody fragments
      were investigated. Combination of Fab fragment as a capture antibody and Mab as a
      detector antibody on a nanoparticle label resulted in high signal-to-background
      ratio consistently. Against the expectations no significant difference in
      nonspecific binding was found using fragmented antibodies compared to Mabs. The
      results also suggested that nonspecific binding was independent of the particle
      size. The particle size had a significant effect on the specific signal favouring
      the use of small particles giving a high specific signal. This study indicated
      that nonspecific binding is not readily affected by the physical size of the
      nanoparticle label or antibodies used in the assay.

PMID- 19379755
TI  - Ontogeny of hemocyanin in the ovoviviparous cockroach Blaptica dubia suggests an
      embryo-specific role in oxygen supply.
AB  - For a long time it had been assumed that specific oxygen transport proteins are
      absent in insects. Only recently it has been demonstrated that hemocyanins occur
      in the hemolymph of many ametabolous and hemimetabolous insect taxa, but not in
      the Eumetabola (Hemiptera+Holometabola). Therefore, the loss of respiratory
      hemocyanin in insects is not correlated with the evolution of an efficient
      tracheal system. The specific contribution of hemocyanin to oxygen supply in
      insects, however, has remained uncertain. Here we investigate the stage-specific
      expression of hemocyanin in the ovoviviparous cockroach Blaptica dubia
      (Blattaria), which consists of two distinct subunit types (Hc1 and Hc2).
      Employing quantitative real-time RT-PCR and Western blotting, we showed that the
      expression of hemocyanin is restricted to late embryos, thus being detectable
      also in whole female extracts and oothecae. Hemocyanin protein is also present in
      1st instar nymphs, but not in later developmental stages. The ontogeny of
      hemocyanin in cockroaches is distinct from that known from Zygentoma and
      Plecoptera, in which hemocyanin occurs in both nymphal and adult stages. Our
      findings suggest a specific role of hemocyanin in embryonic cockroaches, which
      may be related to an enhanced oxygen supply in the oothecae. For some reason, the
      fundamental physiological changes associated to the evolution of holometaboly
      have made hemocyanin unnecessary.

PMID- 19379756
TI  - Ca2+-dependent photocrosslinking of tropomyosin residue 146 to residues 157-163
      in the C-terminal domain of troponin I in reconstituted skeletal muscle thin
      filaments.
AB  - The Ca(2+)-dependent interaction of troponin I (TnI) with actin.tropomyosin (Tm)
      in muscle thin filaments is a critical step in the regulation of muscle
      contraction. Previous studies have suggested that, in the absence of Ca(2+), TnI
      interacts with Tm and actin in reconstituted muscle thin filaments, maintaining
      Tm at the outer domain of actin and blocking myosin-actin interaction. To obtain
      direct evidence for this Tm-TnI interaction, we performed photochemical
      crosslinking studies using Tm labeled with 4-maleimidobenzophenone at position
      146 or 174 (Tm*146 or Tm*174, respectively), reconstituted with actin and
      troponin [composed of TnI, troponin T (TnT), and troponin C] or with actin and
      TnI. After near-UV irradiation, SDS gels of the Tm*146-containing thin filament
      showed three new high-molecular-weight bands determined to be crosslinked
      products Tm*146-TnI, Tm*146-troponin C, and Tm*146-TnT using fluorescence-labeled
      TnI, mass spectrometry, and Western blot analysis. While Tm*146-TnI was produced
      only in the absence of Ca(2+), the production of other crosslinked species did
      not show Ca(2+) dependence. Tm*174 mainly crosslinked to TnT. In the absence of
      actin, a similar crosslinking pattern was obtained with a much lower yield. A
      tryptic peptide from Tm*146-TnI with a molecular mass of 2601.2 Da that was not
      present in the tryptic peptides of Tm*146 or TnI was identified using HPLC and
      matrix-assisted laser desorption/ionization time-of-flight. This was shown, using
      absorption and fluorescence spectroscopy, to be the 4-maleimidobenzophenone
      labeled peptide from Tm crosslinked to TnI peptide 157-163. These data, which
      show that a region in the C-terminal domain of TnI interacts with Tm in the
      absence of Ca(2+), support the hypothesis that a TnI-Tm interaction maintains Tm
      at the outer domain of actin and will help efforts to localize troponin in
      actin.Tm muscle thin filaments.

PMID- 19379758
TI  - Thermal response with exothermic effects of beta2-microglobulin amyloid fibrils
      and fibrillation.
AB  - Calorimetric measurements were carried out using a differential scanning
      calorimeter to characterize the thermal response of beta(2)-microglobulin amyloid
      fibrils, the deposition of which results in dialysis-related amyloidosis. The
      fibril solution showed a large decrease in heat capacity (exothermic effect)
      before the temperature-induced depolymerization of the fibrils, which was
      characterized by a definite dependence on heating rate. To understand the factors
      that determine the heating-rate-dependent thermal response, the concentration
      dependence of polyethylene glycol, which inhibits the association of amyloid
      fibrils with heating, on exothermic effect was examined in detail and showed a
      causal link between the exothermic effect and fibril association. The results
      suggest that the transient association driven by a spatial approach and the
      concomitant dehydration of hydrophobic areas of amyloid fibrils may be
      significant factors determining the thermal response with exothermic effect,
      which has not been observed in calorimetric studies of monomolecular globular
      proteins. The heating-rate-dependent thermal response with the exothermic effect
      was observed not only for other amyloid fibrils formed from amyloid beta-peptides
      but also during the processes of the temperature-induced conversion of beta(2)
      microglobulin protofibrils and hen egg-white lysozyme into amyloid fibrils. These
      results highlight the physics related to the heating-rate-dependent behaviors of
      heat capacity in terms of interactions between the specific structures of amyloid
      fibrils and water molecules.

PMID- 19379757
TI  - X-ray fluorescence microscopy reveals the role of selenium in spermatogenesis.
AB  - Selenium (Se) is a trace element with important roles in human health. Several
      selenoproteins have essential functions in development. However, the cellular and
      tissue distribution of Se remains largely unknown because of the lack of
      analytical techniques that image this element with sufficient sensitivity and
      resolution. Herein, we report that X-ray fluorescence microscopy (XFM) can be
      used to visualize and quantify the tissue, cellular, and subcellular topography
      of Se. We applied this technique to characterize the role of Se in
      spermatogenesis and identified a dramatic Se enrichment specifically in late
      spermatids, a pattern that was not seen in any other elemental maps. This
      enrichment was due to elevated levels of the mitochondrial form of glutathione
      peroxidase 4 and was fully dependent on the supplies of Se by selenoprotein P.
      High-resolution scans revealed that Se concentrated near the lumen side of
      elongating spermatids, where structural components of sperm are formed. During
      spermatogenesis, maximal Se associated with decreased phosphorus, whereas Zn did
      not change. In sperm, Se was primarily in the midpiece and colocalized with Cu
      and Fe. XFM allowed quantification of Se in the midpiece (0.8 fg) and head (0.2
      fg) of individual sperm cells, revealing the ability of sperm cells to handle the
      amounts of this element well above its toxic levels. Overall, the use of XFM
      allowed visualization of tissue and cellular Se and provided important insights
      in the role of this and other trace elements in spermatogenesis.

PMID- 19379759
TI  - Mapping of the lipid-binding and stability properties of the central rod domain
      of human dystrophin.
AB  - Dystrophin is a cytoskeletal protein that confers resistance to the sarcolemma
      against the stress of contraction-relaxation cycles by interacting with
      cytoskeletal and membrane partners. Apart from several proteins, membrane
      phospholipids are a partner of the central rod domain made up of 24 spectrin-like
      repeats, separated into sub-domains by four hinges. We previously showed that
      repeats 1 to 3 bind to membrane anionic phospholipids, while repeats 20 to 24 are
      not able to do so. We focus here on the phospholipid-binding properties of the
      major part of the central rod domain, namely, the sub-domain delineated by hinges
      2 and 3 comprising 16 repeats ranging from repeat 4 to 19 (R4-19). We designed
      and produced multirepeat proteins comprising three to five repeats and report
      their lipid-binding properties as well as their thermal stabilities. When these
      proteins are mixed with liposomes including the anionic lipid phosphatidylserine,
      they form stable protein-vesicle complexes as determined by gel-filtration
      chromatography. The absence of an anionic lipid precludes the formation of such
      complexes. Spectroscopic analyses by circular dichroism and tryptophan
      fluorescence show that, while the alpha-helical secondary structures are not
      modified by the binding, protein trans conformation leads to the movement of
      tryptophan residues into more hydrophobic environments. In addition, the decrease
      in the molar ellipticity ratio at 222/208 nm as observed by circular dichroism
      indicates that lipid binding reduces the inter-helical interactions of
      multirepeat proteins, thus suggesting partly "opened" coiled-coil structures.
      Combining these results with data from our previous studies, we propose a new
      model of the dystrophin molecule lying along the membrane bilayer, in which the
      two sub-domains R1-3 and R4-19 interact with lipids and F-actin, while the distal
      sub-domain R20-24 does not exhibit any interaction. These lipid-binding domains
      should thus maintain a structural link between cytoskeletal actin and sarcolemma
      via the membrane phospholipids.

PMID- 19379760
TI  - Impairment in protein expression profile of testicular steroid receptor
      coregulators in male rat offspring perinatally exposed to Bisphenol A.
AB  - AIMS: Steroid hormones and steroid receptors (SRs) play a crucial role in
      spermatogenesis. Steroid receptor coregulators are the major determinants of SR
      functioning, and any alteration in their expression is known to be associated
      with impaired spermatogenesis. Since Bisphenol A (BPA) exposure leads to an
      impairment of spermatogenesis, we hypothesized that this effect could be
      associated with the altered expression of steroid receptors and their
      coregulators in the testes. The present study describes the effect of perinatal
      exposure of rats to BPA on the expression profile of testicular steroid receptor
      coregulators in the F(1) generation. These effects were further studied in the
      F(2) and F(3) generations to determine vertical transmission. MAIN METHODS:
      Pregnant female rats (F(0)) were gavaged daily with BPA (1.2 and 2.4 microg/kg
      bw) (or vehicles for controls) from gestation day 12 through postnatal day (PND)
      21 to obtain the F(1) and subsequent F(2) and F(3) generations.
      Immunohistochemical localization of steroid receptor coactivator-1 (SRC-1), G
      receptor integrating protein-1 (GRIP-1), p300/CBP/cointegrator-associated protein
      (p/CIP) and nuclear corepressor (NCoR) was carried out in the testes of F(1),
      F(2) and F(3) generation adult rats. KEY FINDINGS: A significant reduction in the
      expression of SRC-1 and NCoR, with a parallel increase in the expression of p/CIP
      and GRIP-1, was observed in the testes of rats exposed perinatally to BPA.
      Surprisingly, a similar pattern was observed in the testes of F(2) and F(3) rats.
      SIGNIFICANCE: Perinatal exposure of male rats to BPA leads to transgenerational
      perturbations in the expression profile of testicular steroid receptor
      coregulators.

PMID- 19379761
TI  - Upregulation of mRNA of retinoid binding protein and fatty acid binding protein
      by cholesterol enriched-diet and effect of ginger on lipid metabolism.
AB  - AIMS: We investigated whether a cholesterol enriched-diet upregulated mRNA
      expression of the lipid metabolism related-proteins, retinoid binding protein
      (RBP), heart fatty acid binding protein (H-FABP), and cutaneous fatty acid
      binding protein (C-FABP), in liver and adipose tissue, and examined the effect of
      ginger on the expression of these genes. MAIN METHODS: The male rats were divided
      into 3 groups. Control rats were fed a standard diet, the cholesterol enriched
      diet group (Chs) was fed a cholesterol enriched-diet, and the cholesterol
      enriched-diet and ginger group (ChGs) was fed a cholesterol enriched-diet and
      ginger (500 mg/day) diet, respectively for 12 weeks. Each mRNA expression level
      was measured as the ratio of each gene relative to the beta-actin expression
      level, using semi-quantitative RT-PCR method. KEY FINDINGS: Cholesterol enriched
      diet developed hepatic steatosis with hyperlipidemia and increased RBP mRNA
      expression in the liver, as well as mRNA expression of RBP, H-FABP, and C-FABP in
      adipose tissue around the left kidney (P<0.05). This is the first report to show
      the upregulation of H-FABP mRNA in adipose tissue in hyperlipidemic rats. RBP
      mRNA was expressed in the liver on ChGs slightly lower than Chs (P=0.078).
      SIGNIFICANCE: These lipid metabolism genes are important indicators of
      hyperlipidemia. Ginger tends to reduce RBP mRNA expression levels in the liver
      and visceral fat in hyperlipidemia, and may improve lipid metabolism.

PMID- 19379762
TI  - Calpain-1 induces apoptosis in pulmonary microvascular endothelial cells under
      septic conditions.
AB  - This study was to investigate the role of calpain in the apoptosis of pulmonary
      microvascular endothelial cells (PMEC) during septic plasma stimulation. Septic
      plasma was collected from endotoxemic mice. In cultured PMEC, incubation with
      septic plasma stimulated calpain activation, increased caspase-3 activity and
      induced apoptotic cell death. These effects of septic plasma were abrogated by
      knockdown of calpain-1 but not calpain-2 using specific siRNA. Consistently,
      treatment with calpain inhibitor-III, or over-expression of calpastatin, an
      endogenous calpain inhibitor significantly decreased apoptosis induced by septic
      plasma. Septic plasma also induced NADPH oxidase activation and reactive oxygen
      species (ROS) production. Inhibiting NADPH oxidase or scavenging ROS attenuated
      calpain activity and decreased apoptosis in PMEC during septic plasma
      stimulation. In summary, our study demonstrates that ROS produced from NADPH
      oxidase stimulates calpain-1 activation, which induces apoptosis under septic
      conditions. Thus, targeting calpain-1/calpastatin may represent a potential
      strategy to protect against endothelial injury in sepsis.

PMID- 19379764
TI  - Synthesis of spiroannulated oligopyrrole macrocycles derived from lithocholic
      acid.
AB  - Two new steroidal spiroannulated calix[4]pyrroles 5 and 10, derived from bile
      acids (lithocholate), were prepared by the acid catalyzed condensation of methyl
      3,3-bis(pyrrol-2-yl)-5beta-cholan-24-oate 3 with carbonyl compounds and with 2,2'
      propane-2,2-diylbis(1H-pyrrole), respectively. The new compounds were fully
      characterized by physicochemical methods.

PMID- 19379763
TI  - FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA.
AB  - Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder
      characterized by aplastic anemia, cancer susceptibility and cellular sensitivity
      to DNA-crosslinking agents. Eight FA proteins (FANCA, -B, -C, -E, -F, -G, -L and 
      M) and three non-FA proteins (FAAP100, FAAP24 and HES1) form the FA nuclear core
      complex that is required for monoubiquitination of the FANCD2-FANCI dimer upon
      DNA damage. The other three FA proteins, FANCD1/BRCA2, FANCJ/BACH1/BRIP1 and
      FANCN/PALB2, act in parallel or downstream of the FANCD2-FANCI dimer. Despite the
      isolation and characterization of several FA proteins, the mechanism by which
      these proteins protect cells from DNA interstrand crosslinking agents has been
      unclear. This is because a majority of the FA proteins lack any recognizable
      functional domains that can provide insight into their function. The recently
      discovered FANCM (Hef) and FANCJ (BRIP1/BACH1) proteins contain helicase domains,
      providing potential insight into the role of FA proteins in DNA repair. FANCM
      with its partner, FAAP24, and FANCJ bind and metabolize a variety of DNA
      substrates. In this review, we focus on the discovery, structure, and function of
      the FANCM-FAAP24 and FANCJ proteins.

PMID- 19379765
TI  - Steroids from the leaves of Chinese Melia azedarach and their cytotoxic effects
      on human cancer cell lines.
AB  - Three new (1-3) and several known (4-6) steroids were isolated from the leaves of
      Chinese Melia azedarach. The structures of the new compounds were elucidated by
      means of spectroscopic methods including 2D NMR techniques and mass spectrometry
      to be (20S)-5,24(28)-ergostadiene-3beta,7alpha,16beta,20-tetrol (1), (20S)-5
      ergostene-3beta,7alpha,16beta,20-tetrol (2), and 2alpha,3beta-dihydro-5-pregnen
      16-one (3). The cytotoxicities of the isolated compounds against three human
      cancer cell lines (A549, H460, U251) were evaluated; only compounds 1, 2, and
      (20S)-5-stigmastene-3beta,7alpha,20-triol (4) were found to show significant
      cyctotoxic effects with IC(50)s from 12.0 to 30.1 microg/mL.

PMID- 19379766
TI  - Effect of short-term exposure to dichlorvos on synaptic plasticity of rat
      hippocampal slices: involvement of acylpeptide hydrolase and alpha(7) nicotinic
      receptors.
AB  - Dichlorvos is the active molecule of the pro-drug metrifonate used to revert the
      cognitive deficits associated with Alzheimer's disease. A few years ago it was
      reported that dichlorvos inhibits the enzyme acylpeptide hydrolase at lower doses
      than those necessary to inhibit acetylcholinesterase to the same extent.
      Therefore, the aim of our investigation was to test the hypothesis that
      dichlorvos can enhance synaptic efficacy through a mechanism that involves
      acylpeptide hydrolase instead of acetylcholinesterase inhibition. We used long
      term potentiation induced in rat hippocampal slices as a model of synaptic
      plasticity. Our results indicate that short-term exposures (20 min) to 50 microM
      dichlorvos enhance long-term potentiation in about 200% compared to the control
      condition. This effect is correlated with approximately 60% inhibition of
      acylpeptide hydrolase activity, whereas acetylcholinesterase activity remains
      unaffected. Paired-pulse facilitation and inhibition experiments indicate that
      dichlorvos does not have any presynaptic effect in the CA3-->CA1 pathway nor
      affect gabaergic interneurons. Interestingly, the application of 100 nM
      methyllicaconitine, an alpha(7) nicotinic receptor antagonist, blocked the
      enhancing effect of dichlorvos on long-term potentiation. These results indicate
      that under the exposure conditions described above, dichlorvos enhances long-term
      potentiation through a postsynaptic mechanism that involves (a) the inhibition of
      the enzyme acylpeptide hydrolase and (b) the modulation of alpha(7) nicotinic
      receptors.

PMID- 19379767
TI  - Cadmium-containing nanoparticles: perspectives on pharmacology and toxicology of
      quantum dots.
AB  - The field of nanotechnology is rapidly expanding with the development of novel
      nanopharmaceuticals that have potential for revolutionizing medical treatment.
      The rapid pace of expansion in this field has exceeded the pace of
      pharmacological and toxicological research on the effects of nanoparticles in the
      biological environment. The development of cadmium-containing nanoparticles,
      known as quantum dots, show great promise for treatment and diagnosis of cancer
      and targeted drug delivery, due to their size-tunable fluorescence and ease of
      functionalization for tissue targeting. However, information on pharmacology and
      toxicology of quantum dots needs much further development, making it difficult to
      assess the risks associated with this new nanotechnology. Further, nanotechnology
      poses yet another risk for toxic cadmium, which will now enter the biological
      realm in nano-form. In this review, we discuss cadmium-containing quantum dots
      and their physicochemical properties at the nano-scale. We summarize the existing
      work on pharmacology and toxicology of cadmium-containing quantum dots and
      discuss perspectives in their utility in disease treatment. Finally, we identify
      critical gaps in our knowledge of cadmium quantum dot toxicity, and how these
      gaps need to be assessed to enable quantum dot nanotechnology to transit safely
      from bench to bedside.

PMID- 19379768
TI  - Cloning and characterization of cDNA sequences encoding for new venom peptides of
      the Brazilian scorpion Opisthacanthus cayaporum.
AB  - Scorpion venom glands produce a large variety of bioactive peptides. This
      communication reports the identification of venom components obtained by
      sequencing clones isolated from a cDNA library prepared with venomous glands of
      the Brazilian scorpion Opisthacanthus cayaporum (Ischnuridae). Two main types of
      components were identified: peptides with toxin-like sequences and proteins
      involved in cellular processes. Using the expressed sequence tag (EST) strategy
      118 clones were identified, from which 61 code for unique sequences (17 contigs
      and 44 singlets) with an average length of 531 base-pairs (bp). These results
      were compared with those previously obtained by the proteomic analysis of the
      same venom, showing a considerable degree of similarity in terms of the molecular
      masses expected and DNA sequences found. About 36% of the ESTs correspond to
      toxin-like peptides and proteins with identifiable open reading frames (ORFs).
      The cDNA sequencing results also show the presence of sequences whose putative
      products correspond to a scorpine-like component; three short antimicrobial
      peptides; three K(+)-channel blockers; and an additional peptide containing 78
      amino acid residues, whose sequence resembles peptide La1 from another
      Ischnuridae scorpion Liocheles australiasiae, thus far with unknown function.

PMID- 19379769
TI  - Sleep and rest facilitate implicit memory in a visual search task.
AB  - Several forms of learning have been demonstrated to show improvements with sleep.
      Based on rodent models, it has been suggested that replay of waking events in the
      hippocampus during sleep may underlie memory consolidation in humans. However,
      behavioral data for the role of sleep in human hippocampal-related memory have
      been inconsistent. To further investigate the role of sleep in hippocampal
      mediated learning, we tested subjects in two sessions of a contextual cueing
      paradigm, a form of hippocampus-dependent implicit learning, separated by
      intervals of sleep, active wake, or carefully controlled quiet rest. Participants
      completed a visual search task, and unbeknownst to them, some search displays
      were occasionally repeated in the experiment. Contextual cueing was revealed by
      faster search speed on repeated trials (Old) than unrepeated ones (New), even
      though subjects were unaware of the trial repetition. Notably, performance in a
      second testing session was equivalent for participants who underwent quiet
      resting, daytime sleep, or nocturnal sleep between the two sessions. These four
      groups showed equivalent transfer of learning from Session 1. Notably, learning
      of New configurations in Session 2 was absent in the active wake group, but was
      equally strong among the other three groups. These results indicate that this
      form of hippocampal learning is independent of sleep, and vulnerable to proactive
      interference during active wake. They prompt a reevaluation of the hippocampal
      replay hypothesis as a general model of sleep-dependent learning.

PMID- 19379770
TI  - Effects of mecamylamine on nicotine-induced conditioned hyperactivity and
      sensitization in differentially reared rats.
AB  - Rats reared in an enriched condition (EC) display less sensitization to nicotine
      than rats reared in an impoverished condition (IC). However, it is unknown what
      effect differential rearing has on nicotine-induced conditioned hyperactivity.
      The present study determined whether differential rearing affects nicotine
      induced conditioned hyperactivity. This study also examined the effects of
      mecamylamine on conditioned hyperactivity and sensitization. EC, IC, and social
      condition (SC) rats were reared from 21 to 51 days of age before receiving
      repeated nicotine injections (.4 mg/kg) prior to 1-h locomotor sessions.
      Following the conditioned-hyperactivity test, rats received additional training
      sessions followed by a drug-free rest period before the sensitization test.
      Mecamylamine (1.0 mg/kg) was administered prior to the conditioned-hyperactivity
      test and sensitization test. Nicotine treatment resulted in sensitization and
      conditioned hyperactivity in all differential rearing groups. EC rats displayed
      less locomotor activity in response to nicotine than both IC and SC rats.
      Pretreatment with mecamylamine blocked the expression of conditioned
      hyperactivity only in EC and SC rats and attenuated sensitization in all three
      rearing groups. These findings suggest that environmental enrichment may alter
      nicotinic acetylcholine receptors during development and may be a protective
      factor in the initiation and relapse of smoking behavior.

PMID- 19379771
TI  - Sex differences in sleep and sleep-dependent learning in abstinent cocaine users.
AB  - Sleep and sleep-dependent learning are impaired in male cocaine users during
      abstinence, but for female users little is known. Cocaine dependent men (n=12)
      and women (n=14), and control participants (n=19) participated in this study of
      sleep and sleep-dependent learning. Cocaine users were assessed at 3, 10 and 20
      days of abstinence and controls were studied over one night. Total sleep time,
      sleep efficiency and overnight motor learning were the main outcome measures.
      Cocaine dependent men compared to women exhibited deteriorations in sleep time,
      sleep efficiency, and overnight learning as abstinence progressed from 3 to 20
      days. At abstinence day 3, cocaine dependent men and women were no different than
      control participants in the main outcomes. However, there were significant
      differences between cocaine men at abstinence day 20 and controls in sleep time
      and sleep-dependent learning, but no differences between controls and cocaine
      dependent women. There is growing evidence that sleep disturbances are associated
      with cocaine abuse and abstinence and have functional consequences that may be
      relevant to the development of effective treatments. The absence of sleep
      disturbances in women suggests a need to understand the mechanisms underlying
      these differences, as such knowledge could lead to novel therapies in cocaine
      dependence.

PMID- 19379772
TI  - A minimally invasive displacement sensor for measuring brain micromotion in 3D
      with nanometer scale resolution.
AB  - Electrophysiological recordings from a single or population of neurons are
      currently the standard method for investigating neural mechanisms with high
      spatio-temporal resolution. It is often difficult or even impossible to obtain
      stable recordings because of brain movements generated by the cardiac and
      respiratory functions and/or motor activity. An alternative approach to extensive
      surgical procedures aimed to reduce these movements would be to develop a control
      system capable of compensating the relative movement between the recording site
      and the electrode. As a first step towards such a system, an accurate method
      capable of measuring brain micromotion, preferably in 3D, in a non-invasive
      manner is required. A wide variety of technical solutions exist for displacement
      measurement. However, increased sensitivity in the measurement is often
      accompanied by strict limitations to sensor handling, implementation and external
      environment. In addition, majority of the current methods are limited to
      measurement along only one axis. We present a novel, minimally invasive, 3D
      displacement sensor with displacement resolution exceeding 70 nm along each axis.
      The sensor is based on optoelectronic detection of movements of a spring-like
      element with three degrees of freedom. It is remarkably compact with needle-like
      probe and can be packaged to withstand considerable mishandling, which allow easy
      implementation to existing measurement systems. We quantify the sensor
      performance and demonstrate its capabilities with an in vivo measurement of
      blowfly brain micromotion in a preparation commonly used for electrophysiology.

PMID- 19379773
TI  - Induction of tolerogenic vs immunogenic dendritic cells (DCs) in the presence of
      GM-CSF is regulated by the strength of signaling from monophosphoryl lipid A
      (MPLA) in association with glutathione and fetal hemoglobin gamma-chain.
AB  - Previous studies showed a fetal sheep liver extract (FSLE), in association with
      monophosphoryl lipid A, MPLA (a bioactive component of lipid A of LPS), could
      interact to induce the development of dendritic cells (DCs) which regulated
      production of Foxp3+ Treg. This interaction was associated with an altered gene
      expression both of distinct subsets of TLRs and of CD200Rs. Prior studies had
      suggested that major interacting components within FSLE were gamma-chain of fetal
      hemoglobin (Hgbgamma) and glutathione (GSH). We investigated whether
      differentiation/maturation of DCs in vitro in the presence of either GM-CSF or
      Flt3L to produce preferentially either immunogenic or tolerogenic DCs was itself
      controlled by an interaction between MPLA, GSH and Hgbgamma. At low
      (approximately 10 microg/ml) Hgbgamma concentrations, DCs developing in culture
      with GSH and MPLA produced optimal stimulation of allogeneic CTL cell responses
      in vitro (and enhanced skin graft rejection in vivo). At higher concentrations
      (>40 microg/ml Hgbgamma) and equivalent concentrations of MPLA and GSH, the DCs
      induce populations of Treg which can suppress the induction of allogeneic CTL and
      graft rejection in vivo. These different populations of DCs express different
      patterns of mRNAs for the CD200R family. Addition of anti-TLR or anti-MD-1 mAbs
      to DCs developing in this mixture (Hgbgamma+GSH+MPLA), suggests that one effect
      of (GSH+Hgbgamma) on MPLA stimulation may involve altered signaling through TLR4.

PMID- 19379774
TI  - Circadian rhythms of basal orexin levels in the hypothalamus are not influenced
      by an impaired corticotropin-releasing hormone receptor type 1 system.
AB  - Wake-promoting effects of orexins and corticotropin-releasing hormone (CRH) are
      well documented. Neuronal interactions between these two systems and anatomical
      data point to a reciprocal influence of these neuropeptides. We examined in how
      far an impaired CRH system may influence the circadian rhythm of extracellular
      orexin levels in mice. The basal levels of orexin were collected unilaterally
      from the lateral hypothalamus over 24 h in conditional CNS-specific CRH receptor
      type 1 (CRH-R1) knockout animals and control littermates. No significant
      differences were obtained between both groups suggesting that under basal
      conditions the circadian variation of hypothalamic orexin is not mediated by CRH,
      at least not via CRH-R1.

PMID- 19379775
TI  - Blue but not red light stimulation in the dark has antidepressant effect in
      behavioral despair.
AB  - The present study investigated potential antidepressant effect of light exposure
      in the dark phase of a 12:12 L/D cycle on behavioral despair. In Exp.1, male
      Wistar rats were administered a single, 10 min broadband light pulse (1300lx)
      either 3h (ZT15) or 9h (ZT21) after dark onset (ZT12) and tested in two
      consecutive swim tests separated by 24 h. Photic stimulation at ZT21 but not ZT15
      significantly reduced immobility in the second swim test relative to the first
      test compared to controls that were treated similarly except for light pulse
      administration (p<0.05). In Exp.2, groups were exposed to a single 10-min light
      pulse (1300lx) either in the blue or red end of the spectrum at ZT21 or were
      treated similarly except for photic exposure (controls). Exposure to blue light
      resulted in significantly reduced duration of immobility in the second swim test
      relative to that of the first test compared to the red light and control groups
      (p<0.05). The present findings suggest a critical role in the antidepressant
      effect of blue light stimulation for the melanopsin-containing ganglion cells in
      the retina that are sensitive to wavelengths in the blue but not red end of the
      visible spectrum.

PMID- 19379777
TI  - Detection of social approach in inbred mice.
AB  - An experiment was designed to automatically assess the relative level of social
      interaction during encounters involving trios of inbred mice consisting of two
      familiar cage mate males plus an unfamiliar third male. The automation of the
      spatial positioning was obtained by using a video-tracking program. In addition
      social behaviours were manually scored. To evaluate the influence of basic motor
      properties on the evaluation of the level of social interaction, we analysed two
      strains (C57BL/6J and 129S2/Sv) that are frequently employed in transgenic
      research, and show very different levels of motor activity. Correlations between
      manual and automated parameters showed that spatial parameters correctly fitted
      the level of social interaction between mice. In both strains C57BL/6J and
      129S2/Sv, a proximity parameter (duration of bouts during which two individuals
      were close to each other) defined the social approach and correctly assessed the
      discrimination of social novelty.

PMID- 19379778
TI  - Use of molecular beacons and multi-allelic real-time PCR for detection of and
      discrimination between virulent Bacillus anthracis and other Bacillus isolates.
AB  - The awareness of the threat of Bacillus anthracis, the causative agent of the
      disease anthrax, as a biowarfare and bioterrorism weapon has revived the
      development of new technologies for rapid and accurate detection of virulent
      isolates in environmental and clinical samples. Here we explore the utility of
      molecular beacon real-time PCR technology for detection of virulent Bacillus
      anthracis strains. Molecular beacons are nucleic acid probes with high
      specificity, that act as switches by emitting fluorescence when bound to their
      nucleotide sequence targets by means of altering their conformation. In this
      study, five molecular beacons targeting Bacillus anthracis capA, capB, capC, lef,
      and pag alleles were designed and used in five uniplex assays. Another molecular
      beacon targeting the Bacillus group chromosomal 16s rRNA allele was designed for
      use in a duplex assay with an internal PCR amplification control. The molecular
      beacons were used in a real-time PCR assay for the detection of and
      differentiation between virulent B. anthracis and other members of the B. cereus
      group at the molecular level. Various B. anthracis samples as well as other
      bacterial and human samples were used to demonstrate the sensitivity and
      specificity of this assay. Use of the molecular beacon real-time PCR technology
      should accelerate current efforts to swiftly detect B. anthracis strains and its
      virulence plasmids in clinical and environmental samples and may extend to the
      development of additional molecular beacon-based assays for the identification of
      other pathogenic agents or the identification of B. anthracis directly from
      clinical samples.

PMID- 19379776
TI  - Animal models of gene-environment interactions in schizophrenia.
AB  - The pathogenesis of schizophrenia and related mental illnesses likely involves
      multiple interactions between susceptibility genes of small effects and
      environmental factors. Gene-environment interactions occur across different
      stages of neurodevelopment to produce heterogeneous clinical and pathological
      manifestations of the disease. The main obstacle for mechanistic studies of gene
      environment interplay has been the paucity of appropriate experimental systems
      for elucidating the molecular pathways that mediate gene-environment interactions
      relevant to schizophrenia. Recent advances in psychiatric genetics and a plethora
      of experimental data from animal studies allow us to suggest a new approach to
      gene-environment interactions in schizophrenia. We propose that animal models
      based on identified genetic mutations and measurable environment factors will
      help advance studies of the molecular mechanisms of gene-environment interplay.

PMID- 19379779
TI  - Angiopoietin-1 induces neurite outgrowth of PC12 cells in a Tie2-independent,
      beta1-integrin-dependent manner.
AB  - Overexpression of angiopoietin (Ang) 1 in the brain results in increased
      vascularization and altered neuronal dendrite configuration. We hypothesized that
      Ang1 acts directly on neurons inducing neurite outgrowth. We stimulated PC12
      cells with Ang1 and observed outgrowth levels comparable to nerve growth factor
      (NGF). Western blotting and RT-PCR demonstrated the absence of the Ang1 receptor,
      Tie2 and the presence of beta1-integrin. Downstream of beta1-integrin, Ang1
      stimulation led to a approximately 2.6 fold increase in focal adhesion kinase
      (FAK) phosphorylation and no change in the activation of mitogen-activated
      protein kinase (MAPK) nor c-Jun N-terminal kinase (JNK). Conversely, NGF
      stimulation had no effect on FAK phosphorylation but led to a approximately 3.1
      and approximately 2 fold increase in phosphorylation of MAPK and JNK. Ang1, but
      not NGF-mediated outgrowth was attenuated following functional inhibition of
      beta1-integrin and FAK, and Wortmannin inhibited neurite outgrowth mediated by
      both. Our results suggest that Ang1 induces neurite outgrowth in PC12 cells in a
      Tie2-independent, beta1-integrin-FAK-PI3K-Akt-dependent manner and that NGF and
      Ang1 mediate neurite outgrowth via two independent signaling mechanisms.

PMID- 19379780
TI  - Angiotensin II type-2 (AT2) receptor antagonism alters cardiovascular responses
      to static exercise and simultaneously changes glutamate/GABA levels within the
      ventrolateral medulla.
AB  - Angiotensin II receptors (Ang II), classified into AT1 and AT2 subtypes, are
      located in different regions of the central nervous system, including the
      cardiovascular control centers in the medulla oblongata. We previously reported
      the role of Ang II AT1 receptors within the medulla on cardiovascular responses
      and glutamate/GABA neurotransmission during the exercise pressor reflex [Patel,
      D., Bohlke, M., Phattanarudee, S., Kabadi, S., Maher, T.J., Ally, A., 2008.
      Cardiovascular responses and neurotransmitter changes during blockade of
      angiotensin II receptors within the ventrolateral medulla. Neurosci. Res. 60 (3),
      340-348]. In this study, we investigated the role of the AT2 receptor subtype
      within the ventrolateral medullary region (VLM) in modulating increases in mean
      arterial pressure (MAP) and heart rate (HR) in response to static skeletal muscle
      contraction. METHODS: Using microdialysis methods in anesthetized rats, we
      administered AR-AT2 antagonists into the rostral (RVLM) and caudal (CVLM) VLM and
      determined its effects on cardiovascular responses and glutamate/GABA
      neurotransmission following muscle contraction. Bilateral microdialysis of a
      selective AT2 antagonist, PD 123319 (10 microM), for 30 min into the RVLM
      augmented MAP and HR responses during a static muscle contraction.
      Simultaneously, the drug increased glutamate and decreased GABA levels within the
      RVLM. After 60 min of discontinuation of the drug, only MAP and HR values but not
      the neurotransmitter levels in response to a muscle contraction returned to
      baseline. In contrast, bilateral microdialysis of the drug into the CVLM
      attenuated cardiovascular responses during a static muscle contraction, decreased
      glutamate and increased GABA. However, only the cardiovascular responses
      recovered after 60 min of discontinuation of the drug. These results demonstrate
      that AT2 within both RVLM and CVLM plays important differential roles in
      modulating neurotransmission and cardiovascular function during the exercise
      pressor reflex.

PMID- 19379781
TI  - Genetic interaction between Neurexin and CAKI/CMG is important for synaptic
      function in Drosophila neuromuscular junction.
AB  - Neurexins are neuron-specific cell surface molecules thought to localize to
      presynaptic membranes. Recent genetic studies using Drosophila melanogaster have
      implicated an essential role for a single Drosophila neurexin (dnrx) in the
      proper architecture, development and function of synapses in vivo. However, the
      precise mechanisms underlying these actions are not fully understood. To
      elucidate the molecular mechanism of Neurexin in vivo, we employed dnrx and caki
      mutant flies, combined with various methods, and analyzed the animals'
      locomotion, synaptic vesicle cycling and neurotransmission of neuromuscular
      junctions. We found that Dneurexin (DNRX) is important for locomotion through a
      genetic interaction with the scaffold protein, CAKI/CMG, the Drosophila homolog
      of vertebrate CASK. Similar to its mammalian counterparts, DNRX is essential for
      synaptic vesicle cycling, which plays critical roles in neurotransmission at
      neuromuscular junctions (NMJ). However, this interaction appears not to be
      required for the synaptic targeting of DNRX, but may instead be needed for proper
      synaptic function, possibly by regulating the synaptic vesicle cycling process.

PMID- 19379782
TI  - alphaB-crystallin suppresses oxidative stress-induced astrocyte apoptosis by
      inhibiting caspase-3 activation.
AB  - alphaB-crystallin is a member of the small heat shock proteins, which is
      abundantly expressed in various vertebrate tissues including the central nervous
      system. In our previous report, we showed alphaB-crystallin induction in
      activated astrocytes in the postischemic brain and in H2O2-treated primary
      astrocyte cultures. To investigate the functional significance of alphaB
      crystallin induction in astrocytes, we generated a stable C6 astroglioma cell
      line overexpressing alphaB-crystallin. In these cells, hydrogen peroxide-induced
      apoptosis was reduced by 60% compared to parent cells. Furthermore, the
      repression of alphaB-crystallin expression by alphaB-crystallin siRNA
      transfection suppressed this protective effect, indicating that alphaB-crystallin
      is responsible for the protection against H2O2-induced apoptosis in C6
      astroglioma cells. Similar level of aggravation in H2O2-induced apoptosis was
      observed in primary astrocyte cultures when alphaB-crystallin expression was
      suppressed by alphaB-crystallin siRNA transfection, confirming the importance of
      alphaB-crystallin. In addition, the induction of caspase-3 activity after H2O2
      treatment was markedly suppressed in alphaB-crystallin-overexpressing cells, and
      immunoprecipitation proved binding between alphaB-crystallin and partially
      processed caspase-3 (a p24 intermediate). These results indicate that alphaB
      crystallin confers protection against hydrogen peroxide-induced astrocytes
      apoptosis in part by inhibiting caspase-3 activation.

PMID- 19379783
TI  - Highly active, citrate inhibition resistant form of Aspergillus niger 6
      phosphofructo-1-kinase encoded by a modified pfkA gene.
AB  - In Aspergillus niger cells spontaneous posttranslational modification of 6
      phosphofructo-1-kinase (PFK1) occurs. In a two step process the native enzyme
      (85kDa) is first cleaved to an inactive fragment (49kDa) that regains its
      activity after phosphorylation of the protein. The shorter PFK1 fragment exhibits
      changed kinetics, such as resistance to citrate inhibition. In order to avoid
      spontaneous complex posttranslational modification, modified gene was prepared
      encoding an active shorter PFK1 fragment. Since no appropriate microbial strains
      with disrupted native pfkA genes were available, Aspergillus niger strain with
      reduced likelihood for spontaneous posttranslational modification of PFK1 has
      been chosen for in vivo tests. First, the appropriate length of a truncated gene
      was defined after a number of enzymes encoded by genes of different lengths had
      been tested. After adding sodium azide to the medium, phosphorylation was induced
      in the transformed hyphae to activate the shorter fragments which were
      subsequently screened for changed PFK1 kinetics. In the second step the
      responsible threonine residue was replaced with glutamic acid to elude the need
      for phosphorylation. An active shorter PFK1 fragment, resistant to citrate
      inhibition and activated to a higher level by fructose-2,6-bisphosphate with
      respect to the native enzyme was encoded directly from the modified gene.

PMID- 19379784
TI  - Papillomavirus DNA complementation in vivo.
AB  - Recent phylogenic studies indicate that DNA recombination could have occurred in
      ancient papillomavirus types. However, no experimental data are available to
      demonstrate this event because of the lack of human papillomavirus infection
      models. We have used the cottontail rabbit papillomavirus (CRPV)/rabbit model to
      study pathogenesis and immunogenicity of different mutant genomes in vivo.
      Although the domestic rabbit is not a natural host for CRPV infection, it is
      possible to initiate infection with naked CRPV DNA cloned into a plasmid and
      monitor papilloma outgrowth on these animals. Taking advantage of a large panel
      of mutants based on a CRPV strain (Hershey CRPV), we tested the hypothesis that
      two non-viable mutant genomes could induce papillomas by either recombination or
      complementation. We found that co-infection with a dysfunctional mutant with an
      E2 transactivation domain mutation and another mutant with an E7 ATG knock out
      generated papillomas in rabbits. DNA extracted from these papillomas contained
      genotypes from both parental genomes. Three additional pairs of dysfunctional
      mutants also showed similar results. Individual wild type genes were also shown
      to rescue the function of corresponding dysfunctional mutants. Therefore, we
      suggest that complementation occurred between these two non-viable mutant PV
      genomes in vivo.

PMID- 19379785
TI  - Biosynthesis and characterization of a novel genetically engineered polymer for
      targeted gene transfer to cancer cells.
AB  - A novel multi-domain biopolymer was designed and genetically engineered with the
      purpose to target and transfect cancer cells. The biopolymer contains at precise
      locations: 1) repeating units of arginine and histidine to condense pDNA and lyse
      endosome membranes, 2) a HER2 targeting affibody to target cancer cells, 3) a pH
      responsive fusogenic peptide to destabilize endosome membranes and enhance
      endosomolytic activity of histidine residues, and 4) a nuclear localization
      signal to enhance translocation of pDNA towards the cell nucleus. The results
      demonstrated that the biopolymer was able to condense pDNA into nanosize
      particles, protect pDNA from serum endonucleases, target HER2 positive cancer
      cells but not HER2 negative ones, efficiently disrupt endosomes, and effectively
      reach the cell nucleus of target cells to mediate gene expression. To reduce
      potential toxicity and enhance biodegradability, the biopolymer was designed to
      be susceptible to digestion by endogenous furin enzymes inside the cells. The
      results revealed no significant biopolymer related toxicity as determined by
      impact on cell viability.

PMID- 19379786
TI  - Antibodies to squalene in US Navy Persian Gulf War veterans with chronic
      multisymptom illness.
AB  - Since the end of the 1991 Gulf War, there have been reports of unexplained,
      multisymptom illnesses afflicting veterans who consistently report more symptoms
      than do nondeployed veterans. One of the many possible exposures suspected of
      causing chronic multisymptom illnesses Gulf War veterans is squalene, thought to
      be present in anthrax vaccine. We examined the relationship between squalene
      antibodies and chronic symptoms reported by Navy construction workers (Seabees),
      n=579. 30.2% were deployers, 7.4% were defined as ill, and 43.5% were positive
      for squalene antibodies. We found no association between squalene antibody status
      and chronic multisymptom illness (p=0.465). The etiology of Gulf War syndrome
      remains unknown, but should not include squalene antibody status.

PMID- 19379787
TI  - One dose of a porcine circovirus 2 (PCV2) sub-unit vaccine administered to 3-week
      old conventional piglets elicits cell-mediated immunity and significantly reduces
      PCV2 viremia in an experimental model.
AB  - The immunogenicity and efficacy generated by one dose of a PCV2 sub-unit vaccine
      (Porcilis PCV) were evaluated in 3-week-old conventional piglets. Vaccination
      induced both humoral and cell-mediated responses against PCV2, which were
      increased after the challenge with a PCV2 genotype "b" isolate. High levels of
      maternally derived antibodies (IPMA >or= 10 log(2)) at the time of vaccination
      were found to interfere with the active seroconversion, whereas titres below 8
      log(2) allowed the development of a proper antibody response. Nevertheless, the
      immunity induced by one dose of the product was partly protective against PCV2
      infection, since viremia, shedding and viral load in tissues were significantly
      reduced in vaccinated pigs compared to controls.

PMID- 19379788
TI  - Neonatal vaccination with Mycobacterium bovis BCG: potential effects as a priming
      agent shown in a heterologous prime-boost immunization protocol.
AB  - In general prime-boost immunization including Mycobacterium bovis bacille
      Calmette-Guerin (BCG) as a priming agent has been a recent successful strategy in
      animal models. However, the effects of BCG as a priming vaccine have not been
      investigated systematically. Thus, we modelled a heterologous prime-boost
      immunization in mice with BCG administered at the neonatal period and
      mycobacterial heparin-binding hemagglutinin (HBHA) at adult ages. Mice were
      challenged with a high dose of BCG (10(7) colony forming units) via intranasal
      (i.n.) route. We addressed whether the route of administration and addition of
      adjuvants could be of importance in HBHA-immunizations while animals were primed
      with BCG. Our results showed that prime-boost immunization induced significantly
      higher levels of protection in animals compared to the group vaccinated with BCG
      alone. Most importantly, the levels of protection were comparable between the
      i.n. and subcutaneous (s.c.) boostings with native (n) HBHA and the
      coadministration of adjuvant was not necessary. Moreover, priming with BCG
      improved also the protection promoted by the recombinant form of HBHA, even if to
      a lower degree to that observed after nHBHA boosting. In general, vaccination
      with BCG prior to the HBHA administration was found to contribute in two ways: it
      primed the immune system and provided adjuvant effect. We discuss the several
      outcomes following neonatal BCG priming and HBHA boosting for better protection
      against tuberculosis.

PMID- 19379789
TI  - Effects of particulate matter (PM(10), PM(2.5) and PM(1)) on the cardiovascular
      system.
AB  - Several studies have demonstrated that exposure to particulate matter (PM) of
      different size fractions is associated with an increased risk of cardiovascular
      disease (CVD). In this review, we have taken into consideration the possible
      correlation between the "short term" and "long term" effects of PM exposure and
      the onset of CVDs as well as the possible molecular mechanisms by which PM
      elicits the development of these events. Particularly, it is here underlined that
      these adverse health effects depend not only on the level of PM concentration in
      the air but also on its particular internal composition. Furthermore, we have
      also synthesized the findings gleaned from those few studies indicating that PM
      produced by tobacco smoke can give rise to cardiovascular injury.

PMID- 19379790
TI  - Effect of different regions of Nogo-A on the differentiation of neural
      progenitors.
AB  - Nogo-A is an inhibitor of neurite outgrowth and axonal regeneration after CNS
      injury. Several functional regions including Nogo-66 were identified to mediate
      the inhibitory effect of Nogo-A. We have reported that Nogo-66 could promote
      neural progenitors to differentiate into glial cells. Here we exam three other
      regions of Nogo-A and show two of them also mediate the differentiation of neural
      progenitors. A 172-residues N-terminal region and a 37-residues C-terminal region
      of Nogo-A both could inhibit neuronal differentiation and promoted glial cell
      formation. This study illustrated that Nogo-A had multiple functional domains on
      the behavior of neuronal cells. The inhibitory effect of neural differentiation
      of Nogo-A may also contribute to its restraint of CNS repair.

PMID- 19379791
TI  - Mislocalization of TDP-43 in the G93A mutant SOD1 transgenic mouse model of ALS.
AB  - Previous evidence demonstrates that TAR DNA binding protein (TDP-43)
      mislocalization is a key pathological feature of amyotrophic lateral sclerosis
      (ALS). TDP-43 normally shows nuclear localization, but in CNS tissue from
      patients who died with ALS this protein mislocalizes to the cytoplasm. Disease
      specific TDP-43 species have also been reported to include hyperphosphorylated
      TDP-43, as well as a C-terminal fragment. Whether these abnormal TDP-43 features
      are present in patients with SOD1-related familial ALS (fALS), or in mutant SOD1
      over-expressing transgenic mouse models of ALS remains controversial. Here we
      investigate TDP-43 pathology in transgenic mice expressing the G93A mutant form
      of SOD1. In contrast to previous reports we observe redistribution of TDP-43 to
      the cytoplasm of motor neurons in mutant SOD1 transgenic mice, but this is seen
      only in mice having advanced disease. Furthermore, we also observe rounded TDP-43
      immunoreactive inclusions associated with intense ubiquitin immunoreactivity in
      lumbar spinal cord at end stage disease in mSOD mice. These data indicate that
      TDP-43 mislocalization and ubiquitination are present in end stage mSOD mice.
      However, we do not observe C-terminal TDP-43 fragments nor TDP-43
      hyperphosphorylated species in these end stage mSOD mice. Our findings indicate
      that G93A mutant SOD1 transgenic mice recapitulate some key pathological, but not
      all biochemical hallmarks, of TDP-43 pathology previously observed in human ALS.
      These studies suggest motor neuron degeneration in the mutant SOD1 transgenic
      mice is associated with TDP-43 histopathology.

PMID- 19379792
TI  - In vivo micro-CT imaging of rat brain glioma: a comparison with 3T MRI and
      histology.
AB  - The aim of this study was to evaluate the potential of a novel micro-CT system to
      image in vivo the extent of tumor in a rat model of malignant glioma compared to
      3T magnetic resonance imaging (MRI) and histology. Fourteen animals underwent
      double dose contrast-enhanced imaging with micro-CT and 3T MRI using a clinical
      machine at day 10 after stereotactic F98 glioma cell implantation. Calculation of
      the volume of the contrast-uptaking part of the tumor was done by manually
      outlining the tumor contours by two experienced neuroradiologists. The micro-CT-
      and MRI-derived tumor volumes were compared to histology as gold standard
      (hematoxylin and eosin staining and fluorescence staining). There was high
      interobserver reability regarding the tumor volumes (Crombach's alpha>0.81).
      Also, there was good correlation of micro-CT- and high-field MRI-derived tumor
      volumes compared to histology: 72+/-21 mm3 and 69+/-23 mm3 compared to 81+/-14
      mm3, respectively (r>0.76). Both the micro-CT- and MRI-derived tumor volumes were
      not significantly smaller compared to histology (P>0.14). In conclusion, micro-CT
      allows in vivo imaging of the contrast-enhancing part of experimental gliomas
      with an accuracy comparable to high-field MRI.

PMID- 19379793
TI  - Natural split-brain? Lateralized memory for task contingencies in pigeons.
AB  - The motion aftereffect (MAE) is an illusory motion in the opposite direction
      after the sudden halt of a prolonged visual moving stimulus. Birds could perceive
      the MAE as humans and other mammals. The present study was to investigate whether
      hemispheric asymmetries of visual processes affect this illusion. To this end,
      pigeons were trained to discriminate grating patterns which moved up, or down or
      stood still. The transfer tests were conducted under the binocular or monocular
      viewing condition. The choice behaviors of pigeons under the binocular and right
      eye viewing condition (left hemisphere) were highly indicative for the perception
      of a MAE. However, the animals under the left-eye viewing condition (right
      hemisphere) did not change their choice patterns according to the different task
      displayed on the central stimulus key, but always stuck to the default option of
      pecking the response key ipsilateral to the open eye. We assume that memory for
      task contingencies were confined to the left hemisphere and could not be reached
      by the right half brain due to the absence of the corpus callosum.

PMID- 19379794
TI  - The process of inducing GFAP aggregates in astrocytoma-derived cells is different
      between R239C and R416W mutant GFAP. A time-lapse recording study.
AB  - Alexander disease (ALX) is a rare neurodegenerative disease caused by the gene
      mutations encoding glial fibrillary acidic protein (GFAP). The formation of
      aggregates in the cytoplasm of astrocytes, which mainly consists of GFAP, is
      characteristic of ALX. To examine the dynamic process of aggregates between the
      different domains of GFAP, we performed time-lapse recording on two different
      mutant GFAP. R239C and R416W GFAP mutations located in the rod domain and tail
      domain, respectively, were transfected into astrocytoma-derived cells, and their
      real-time dynamics were observed using time-lapse recording. Our time-lapse
      recording study indicated that the process of inducing aggregates would be
      different between R239C and R416W. In GFP-R239C cells, 32.4% first appeared as
      aggregates, and clusters of aggregates in the cytoplasm tended to move inward and
      form amorphous aggregates. On the other hand, 82.0% of GFP-R416W cells first
      showed disrupted GFAP, with a bubble-like or ring-like structure; however, most
      cells maintained their structure and were capable of cell division. Our result
      indicates that the mechanism of GFAP aggregation depends on the domain in which
      the point mutation is located. A different approach to ALX therapy should be
      considered according to the domain of GFAP.

PMID- 19379795
TI  - Generation of retinal cells from mouse and human induced pluripotent stem cells.
AB  - We previously reported a technique for generating retinal pigment epithelia (RPE)
      and putative photoreceptors from embryonic stem (ES) cells. Here we tested
      whether our procedure can promote retinal differentiation of mouse and human
      induced pluripotent stem cells (iPSCs). Treating iPSCs with Wnt and Nodal
      antagonists in suspension culture induced expression of markers of retinal
      progenitor cells and generated RPE cells. Subsequently, treatment with retinoic
      acid and taurine generated cells positive for photoreceptor markers in all but
      one human cell lines. We propose that iPSCs can be induced to differentiate into
      retinal cells which have a possibility to be used as patient-specific donor cells
      for transplantation therapies.

PMID- 19379797
TI  - Composition and biological activity of essential oil of Achillea ligustica All.
      (Asteraceae) naturalized in central Italy: ideal candidate for anti-cariogenic
      formulations.
AB  - Essential oil from flowers (FL) and vegetative parts (VP) of Achillea ligustica
      (Asteraceae), naturalized after cultivation in central Italy, was investigated by
      GC-FID and GC-MS. The most abundant components were linalool, viridiflorol, beta
      pinene, 1,8-cineole and terpinen-4-ol. The antioxidant assays (DPPH and ABTS
      radical scavenging assays, and beta-carotene bleaching test) demonstrated a
      moderate activity of essential oils. The antimicrobial activity was evaluated by
      the broth micro-dilution method on 6 microbial strains and showed to be quite
      strong against the cariogenic Gram-positive Streptococcus mutans, suggesting that
      this essential oil could be a valid candidate for anti-cariogenic formulations.
      Moderate cytotoxic activity was observed in assays on four tumour cell lines by
      MTT assay.

PMID- 19379796
TI  - Rodent models of glaucoma.
AB  - Glaucoma is a progressive, age-related optic neuropathy and a leading cause of
      irreversible blindness in the world. Animal models of glaucoma are essential to
      our continued efforts of elucidating the natural course of the disease and to
      developing therapeutic interventions to halt or reverse the progression of the
      condition. Over the past 10-15 years, rodents have become a popular model
      organism to study glaucoma, because of their high degree of availability,
      relatively low cost, short life-span, and amenability to experimental and genetic
      manipulation. In this review, we examine the numerous in vivo and in vitro rodent
      models of glaucoma, discuss the methods used to generate them, summarize some of
      the major findings obtained in these models, and identify individual strengths
      and weaknesses for the various systems.

PMID- 19379798
TI  - Sex recognition by male Andrew's toad Bufo andrewsi in a subtropical montane
      region.
AB  - Sex recognition is important for successful reproduction and species usually have
      efficient systems of signals and responses to find the optimal potential mate. In
      the present study, we investigated the ability of males to recognize between
      sexes for two stimulus animals in Andrew's toad Bufo andrewsi, a species widely
      distributed in western China. When a male was placed with a gravid female and a
      similar-sized male, the male did not discriminate between them. When two males
      with distinct size differences were provided with a male, the male chose the
      larger one. In an experiment in which a gravid female and a different-sized male
      were offered a test male, males preferred the larger gravid females than smaller
      males. If a test male clasped a stimulus male, the stimulus male uttered a
      specific release call that caused the test male to release the stimulus male.
      These findings suggest that male B. andrewsi can recognize between the sexes
      probably based on male release calls, and prefer to mate with larger individuals
      with visual cues.

PMID- 19379799
TI  - Spontaneous alternation in marine crabs: invasive versus native species.
AB  - Organisms ranging from paramecia to humans tend to explore places that have been
      least recently explored, which is referred to as spontaneous alternation.
      Although organisms rely on different sources of information in alternating
      between places, the emergent behavioral pattern is likely advantageous during
      exploration and foraging. Under this rationale, continuous spontaneous
      alternation performance of the invasive green crab, Carcinus maenas was assessed
      and compared with the native blue crab, Callinectes sapidus in a plus-maze
      submerged in seawater. For the first time spontaneous alternation behavior was
      demonstrated in Crustacea (i.e., C. maenas) and significant interspecific
      differences in alternation performance were observed between the invasive versus
      the native species. Carcinus maneas exhibited a pronouncedly higher spontaneous
      alternation performance than C. sapidus. Carcinus maneas on average alternated at
      levels higher than chance, which was not the case for C. sapidus. These
      observations point to an additional behavioral mechanism that might result in the
      competitive success of green crabs over blue crabs in areas where they co-occur.
      Most of the subjects exhibited asymptotic alternation performance from the onset;
      there was no improvement in their performance over the course of the experimental
      session. This finding implies the innate nature of this behavioral policy.

PMID- 19379800
TI  - Activation of antioxidant defense during dehydration stress in the African clawed
      frog.
AB  - The glutathione S-transferase (GST) and aldo-keto reductase (AKR) families of
      proteins are major groups of detoxifying enzymes that are known to be regulated
      by the NF-E2 related factor 2 (Nrf2) transcription factor via the antioxidant
      response element that is present in the promoter regions of GST and AKR genes.
      Expression of Nrf2, GST and AKR proteins was analyzed in the African clawed frog,
      Xenopus laevis, focusing on their responses to dehydration stress.
      Dehydration/rehydration cycles can generate oxidative stress and this could be
      ameliorated by enhancing antioxidant defenses. Dehydration to 28% of total body
      water lost triggered organ-specific changes in nrf2 mRNA expression (a 2-fold
      increase in liver), total Nrf2 protein (2-4-fold elevation in lung, heart, skin
      and liver), and a 4.3-fold increase in the content of Nrf2 in the nucleus in
      muscle. Protein levels of six GST and three AKR family members were assessed and
      showed organ-specific patterns of expression during dehydration. In particular,
      GSTP1 was strongly induced in liver, heart and skin, levels rising by 9-, 2.6-
      and 1.7-fold, respectively, whereas GSTM1 and M3 rose in skeletal muscle, kidney
      and skin. Selective expression of GSTK1, A3 and T1 also occurred. Dehydration
      also stimulated organ-specific increases in the levels of AKR family members
      (AKR1B4, AKR1A3, AFAR1) by 1.5-2-fold. The results show that metabolic responses
      to dehydration include activation of the Nrf2 transcription factor and selective
      up-regulation of genes under Nrf2 control.

PMID- 19379801
TI  - Cadmium exposure during pregnancy reduces birth weight and increases maternal and
      foetal glucocorticoids.
AB  - Cadmium exposure induces low birth weight through unknown mechanisms. Since low
      birth weight is associated to foetal exposure to high glucocorticoids (GC)
      concentrations, we hypothesized that low birth weight induced by prenatal
      exposure to Cd(2+) is, at least in part, mediated by higher foetal exposure to
      GC, specifically corticosterone, the main active GC in rodents. Pregnant rats
      were exposed to different dose of CdCl(2) administered in drinking water during
      the whole pregnancy period. At term, corticosterone was measured by enzyme
      immunoassay in maternal and foetal blood and in placental tissues. Cadmium was
      determined in placentas, maternal tissues (liver and kidney) and foetuses by
      inductively coupled plasma-mass spectrometry (ICP-MS). Placental 11beta
      hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity and expression were
      determined by a radiometric conversion assay and quantitative RT-PCR
      respectively. Results demonstrated that 50 ppm of Cd(2+), which was accumulated
      in different maternal tissues but not in the foetus, reduced pup birth weights
      and increased plasma corticosterone concentrations, both in mother and foetus.
      Placental 11beta-HSD2 activity and expression did not change by the treatment. We
      conclude that 50 ppm of Cd(2+) administered during pregnancy, increase foetal
      corticosterone concentrations due, probably, to alterations of the regulatory
      mechanisms of placental barrier to GC causing a mild but significant reduced
      birth weight.

PMID- 19379803
TI  - Comparison of the thermogravimetric analysis (TGA) and Franz cell methods to
      assess dermal diffusion of volatile chemicals.
AB  - Recent work in our laboratory shows that it is possible to measure the minute
      weight changes of skin during exposure to chemical vapor using the
      thermogravimetric analysis (TGA) method. Further, the TGA weight curves can be
      analyzed with a two-compartment diffusion model, yielding two sets of diffusion
      and skin:air partition coefficients. In this study, the dermal diffusion of six
      chemical vapors (n-butanol, cyclohexanone, ethyl benzene, n-hexane, styrene and m
      xylene) were studied by the TGA method using neonatal pig skin. The penetration
      of the six substances was also studied using conventional Franz diffusion cells
      and neat, liquid chemical. A combined analysis of the data, along with previously
      published data on four additional substances (n-butyl acetate, methanol, 2
      propanol and toluene) suggest a good agreement between the TGA and the Franz cell
      methods with respect to diffusion coefficients. An interesting observation is
      that correction of the TGA-derived diffusion coefficients by the octanol:water
      partition coefficient improves the agreement with the Franz cell-derived
      coefficients. TGA-data for seven of the substances were further compared with
      dermal diffusion studies on chemical vapor reported by other investigators. The
      comparisons show good agreement with respect to permeability as well as skin:air
      partition coefficients. In conclusion, it appears that good estimates of
      diffusion coefficients as well as skin:air and permeability coefficients can be
      derived for volatile chemicals with the TGA technique.

PMID- 19379802
TI  - Estradiol promotes proliferation of dopaminergic precursors resulting in a higher
      proportion of dopamine neurons derived from mouse embryonic stem cells.
AB  - Estradiol protects dopamine neurons of the substantia nigra from toxic insults.
      Such neurons succumb in Parkinson's disease; one strategy for restoring dopamine
      deficiency is cell therapy with neurons differentiated from embryonic stem cells.
      We investigated the effects of 17beta-estradiol on dopaminergic induction of
      embryonic stem cells using the 5-stage protocol. Cells were incubated with
      different steroid concentrations during the proliferation (stage 4) or
      differentiation (stage 5) phases. Estradiol added at nM concentrations only
      during stage 4 increases the proliferation of dopaminergic precursors expressing
      Lmx1a, inducing a higher proportion of dopamine neurons at stage 5. These actions
      were mediated by activation of estrogen receptors, because co-incubation of cells
      with estradiol and ICI 182,780 completely abolished the positive effect on both
      proliferation of committed precursors, and subsequent differentiation to
      dopaminergic neurons. Our results suggest that estradiol should be useful in
      producing higher proportions of dopamine neurons from embryonic stem cells aimed
      for treating Parkinson's disease.

PMID- 19379804
TI  - Estimating the age of retrotransposon subfamilies using maximum likelihood.
AB  - We present a maximum likelihood model to estimate the age of retrotransposon
      subfamilies. This method is designed around a master gene model which assumes a
      constant retrotransposition rate. The statistical properties of this model and an
      ad hoc estimation procedure are compared using two simulated data sets. We also
      test whether each estimation procedure is robust to violation of the master gene
      model. According to our results, both estimation procedures are accurate under
      the master gene model. While both methods tend to overestimate ages under the
      intermediate model, the maximum likelihood estimate is significantly less
      inflated than the ad hoc estimate. We estimate the ages of two subfamilies of
      human-specific LINE-I insertions using both estimation procedures. By calculating
      confidence intervals around the maximum likelihood estimate, our model can both
      provide an estimate of retrotransposon subfamily age and describe the range of
      subfamily ages consistent with the data.

PMID- 19379805
TI  - ROS in the aging male: model diseases with ROS-related pathophysiology.
AB  - The aging process is a complex biological phenomenon that can be attributed to
      several mechanisms. ROS (reactive oxygen species) activity is widely considered
      one of them, as it is associated with extensive damage in a variety of cells. For
      example, the gradual decrease in fertility often accompanying aging males can be
      traced back to oxidative stress, since ROS are released throughout life from the
      mitochondrial respiratory chain. Cumulative intracellular damage as a result of
      the increased ROS concentration affects all tissues that perform aerobic
      metabolism and, owing to blood circulation, anaerobic tissues as well. Naturally,
      other mechanisms such as cell inflammation and lack or incapacity of antioxidant
      enzymes also contribute to the variety of systematic distortions that
      characterize aging. Finally, the particularly elevated number of adult men that
      show, among others, a gradual deterioration in reproductive functions suggests a
      central role of ROS generation in senescence in general and male aging, in
      particular.

PMID- 19379806
TI  - Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor
      affecting prenatal development.
AB  - PURPOSE: Treatment-related signs of maternal toxicity, intrauterine growth
      retardation, increased skeletal developmental variations, and decreased bone
      ossification have been reported previously in rats exposed to high doses of non
      selective cyclooxygenase (COX) inhibitors (ibuprofen, piroxicam, and tolmetin),
      also known as nonsteroidal anti-inflammatory drugs (NSAID). On the other hand,
      decrease in fetal length has been the only sign of toxicity found after exposure
      to selective COX-2 inhibitor (DFU). The aim of the study was to evaluate maternal
      effects on selected developmental abnormalities. METHODS: Data on
      postimplantation loss, fetal weight and length, placental weight, external and
      skeletal malformations and developmental variations were examined in the control
      and common COX-inhibitors-exposed groups, in relation to selected maternal blood
      biochemical parameters. RESULTS: Abnormal maternal urea level was found in
      mothers that gave birth to litters with low fetal weights and high incidence of
      skeletal malformations. Increased incidence of developmental variations and
      higher placental weights were also noted in this group. The number of litters
      with postimplantation loss, external malformations, external and skeletal
      variations was higher for dams with abnormal urea levels. A high incidence of
      external developmental variations was also seen in the offspring of dams with
      abnormal protein level. The highest embryo and/or fetal mortality were revealed
      in litters of dams with high urea and low total protein levels, simultaneously.
      In utero exposure to the examined COX-inhibitors increased the risk of
      developmental skeletal variations (OR=1.74). CONCLUSION: Maternal toxicity is an
      important factor affecting prenatal development during in utero exposure to
      nonsteroidal anti-inflammatory drugs.

PMID- 19379807
TI  - Developmental toxicity testing of monoclonal antibodies: an enhanced pre- and
      postnatal study design option.
AB  - For many monoclonal antibodies (mAb), the preferred species for general and
      reproductive safety testing is often the cynomolgus monkey. This article
      describes the rationale for combining the traditional "segmented" embryofetal
      development study with the pre- and postnatal development (PPND) study into a
      single "enhanced" PPND study design in the cynomolgus monkey where a single
      cohort of animals is exposed throughout gestation and allowed to give birth
      naturally. The proposed "enhanced" PPND study design evaluates all the stages of
      the traditional two study design using fewer animals. It also assesses the
      functional consequences of mid to late gestational exposure. This is of
      particular relevance to the risk assessment of monoclonal antibodies where fetal
      exposure to maternal IgG increases as pregnancy progresses and where morphologic
      examination of a pre-term fetus may not be adequate to reveal the presence of
      adverse effects on functional development of key target organs.

PMID- 19379808
TI  - Interplay between the heat shock response and translation in Escherichia coli.
AB  - It is widely accepted that the heat shock response is critical for quality
      control of mature proteins. This function is carried out mainly by chaperones and
      proteases. Recently, a new group of conserved heat shock proteins essential for
      growth at high temperature has been characterized. These proteins are involved in
      regulating and maintaining efficient translation under heat shock.

PMID- 19379809
TI  - Genomic analysis of the adenylate cyclase-hemolysin C-terminal region of
      Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.
AB  - Adenylate cyclase-hemolysin plays an important role in the virulence of
      Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica
      species. Its C-terminal region carries protective epitopes and receptor binding
      site for human cells. Genomic analyses of this region indicate no polymorphism in
      B. pertussis and B. parapertussis regions, but substantial variability in B.
      bronchiseptica that might be linked to the various niches of this species.

PMID- 19379810
TI  - Editorial: an update on the bacterial stress response.

PMID- 19379811
TI  - Classification of the flow regimes in the flow-through cell.
AB  - This paper examines the dissolution apparatus referred to as the flow-through
      cell from an engineering fluid mechanics viewpoint. The analysis demonstrates
      that laminar flow predominantly occurs in the standard operation of this
      apparatus. It is argued that fully turbulent conditions are unlikely.
      Consequently, the phrases 'open column' and 'packed column' are suggested as
      technically more accurate terms for its operational characteristics than the
      conventionally referenced 'turbulent mode' and 'laminar mode'. Examples of flow
      profiles are given to show that the criterion of a "sinusoidal" input flow
      profile required by USP is not a sufficiently accurate characterization at the
      inlet as numerous profiles can be conceived which have the same average flow
      rate. The rationale of pulsating flows versus constant, steady flows is
      discussed. Examples of how references to turbulence in the dissolution-related
      literature can lead to ambiguities and/or inconsistencies are highlighted.

PMID- 19379812
TI  - Quantifying drug release from PLGA nanoparticulates.
AB  - The objective of this work was to investigate the mechanism of release of active
      pharmaceutical ingredients (APIs) both small molecules (ketoprofen, indomethacin,
      coumarin-6) and macromolecules (human serum albumin, ovalbumin), from PLGA
      (50:50) nanoparticulates (400-700nm), having drug loadings less than 10%. The
      nanoparticulates were prepared by emulsification/solvent evaporation methods and
      release determined in phosphate buffer pH 7.4 at 37 degrees C. The release
      profiles exhibited an initial burst release phase, a slower lag phase and a
      second increased release rate phase. The profiles were consistent with a model in
      which the first phase of the release reflects diffusion controlled dissolution of
      drug accessible to the solid/dissolution medium interface and the second phase
      reflects release of drug entrapped in the polymer, the release of which was
      dependent on the bulk degradation of the polymer. The burst phase tended to
      increase with increase in API loading and solubility. The polymer erosion related
      parameters also indicated that increased drug loading accelerated this phase of
      API release. Small acidic hydrophobic actives such as ketoprofen and indomethacin
      had a much greater effect on these parameters than the larger hydrophilic more
      neutral proteins, HSA and ovalbumin.

PMID- 19379813
TI  - Glutamine inhibits ammonia-induced accumulation of cGMP in rat striatum limiting
      arginine supply for NO synthesis.
AB  - Brain L-glutamine (Gln) accumulation and increased activity of the NO/cGMP
      pathway are immediate consequences of acute exposure to ammonia. This study
      tested whether excess Gln may influence NO and/or cGMP synthesis. Intrastriatal
      administration of the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine or the
      system A-specific Gln uptake inhibitor methylaminoisobutyrate increased
      microdialysate Gln concentration and reduced basal and ammonia-induced NO and
      cGMP accumulation. Gln applied in vivo (via microdialysis) or in vitro (to rat
      brain cortical slices) reduced NO and cGMP accumulation in the presence and/or
      absence of ammonia, but not cGMP synthesis induced by the NO donor sodium
      nitroprusside. Attenuation of cGMP synthesis by Gln was prevented by
      administration of L-arginine (Arg). The L-arginine co-substrates of y(+)LAT2
      transport system, L-leucine and cyclo-leucine, mimicked the effect of exogenous
      Gln, suggesting that Gln limits Arg supply for NO synthesis by interfering with
      y+LAT2-mediated Arg uptake across the cell membrane.

PMID- 19379814
TI  - GSK3beta, a centre-staged kinase in neuropsychiatric disorders, modulates long
      term memory by inhibitory phosphorylation at serine-9.
AB  - Accumulating evidence implicates deregulation of GSK3ss as a converging
      pathological event in Alzheimer's disease and in neuropsychiatric disorders,
      including bipolar disorder and schizophrenia. Although these neurological
      disorders share cognitive dysfunction as a hallmark, the role of GSK3ss in
      learning and memory remains to be explored in depth. We here report increased
      phosphorylation of GSK3ss at Serine-9 following cognitive training in two
      different hippocampus dependent cognitive tasks, i.e. inhibitory avoidance and
      novel object recognition task. Conversely, transgenic mice expressing the
      phosphorylation defective mutant GSK3ss[S9A] show impaired memory in these tasks.
      Furthermore, GSK3ss[S9A] mice displayed impaired hippocampal L-LTP and
      facilitated LTD. Application of actinomycin, but not anisomycin, mimicked
      GSK3ss[S9A] induced defects in L-LTP, suggesting that transcriptional activation
      is affected. This was further supported by decreased expression of the immediate
      early gene c-Fos, a target gene of CREB. The combined data demonstrate a role for
      GSK3ss in long term memory formation, by inhibitory phosphorylation at Serine-9.
      The findings are fundamentally important and relevant in the search for
      therapeutic strategies in neurological disorders associated with cognitive
      impairment and deregulated GSK3ss signaling, including AD, bipolar disorder and
      schizophrenia.

PMID- 19379815
TI  - The importance of getting a good start: gestational nutrition interacts with
      adult nutrition to affect function of the aging brain.

PMID- 19379816
TI  - Characterization, kinetics, and possible function of Kazal-type proteinase
      inhibitors of Chinese white shrimp, Fenneropenaeus chinensis.
AB  - Serine proteinase inhibitor plays an essential role in arthropods by restraining
      the activities of endogenic or exogenic serine proteinases. Four Kazal-type
      serine proteinase inhibitors, Fcspi-1-4, from the hepatopancreas of Chinese white
      shrimp, Fenneropenaeus chinensis, were cloned and identified. The open reading
      frames (ORFs) of Fcspis are 1389, 1236, 1080, and 939 base pairs, encode the pre
      proteins of 462, 411, 359, and 312 amino acids and form the 9, 8, 7, and 6
      typical Kazal domains, respectively. When analyzing the amino acid sequences of
      the four inhibitors, it was found that they might have been derived from the same
      transcript, which was subjected to alternative splicing, and none of the Kazal
      domains were identical within each inhibitor. Multiple alignments showed that the
      Kazal inhibitors were homologous with a conserved motif of
      Cx(3)Cx(6)VCGSDGxTYx(3)CxLx(5)Cx(5)ITx(6)GC. The results from RT-PCR indicated
      that the expression of Fcspis as a whole was upregulated by bacterial challenge,
      no obvious change was noticed after viral challenge, and Fcspi-1 had a similar
      expression pattern with that of Fcspis. Recombinant FcSPIs were successfully
      expressed in bacteria and purified for further study. Recombinant FcSPI-1 was
      sensitive to DTT and had thermal stability. The inhibitory kinetics assay
      suggested that rFcSPI-1 was a mixed-type fast tight binding inhibitor with
      inhibitory activities against subtilisin A at a molar ratio of 1:1, 1:2 against
      proteinase K, and 2:1 against elastase. It can firmly bound to two Gram-positive
      and one Gram-negative bacteria but without anti-bacterial ability. In addition,
      it inhibited the activities of both bacterial-secreted proteinases and natural
      chymotrypsin of Chinese white shrimp, suggesting that FcSPI-1 may participate in
      the immune defence response by inhibition of bacterial pathogen proteinases and
      possibly be involved in the regulation of shrimp proteinase activity.

PMID- 19379817
TI  - Cortical depth dependence and implications on the neuronal specificity of the
      functional apparent diffusion coefficient contrast.
AB  - Although the blood oxygenation level-dependent (BOLD) contrast is widely used in
      functional MRI (fMRI), its spatial specificity is compromised by the diversity of
      the participating vasculature, including large draining veins. Previous studies
      have shown that an alternative contrast mechanism based on functional changes of
      the apparent diffusion coefficient (ADC) can be sensitized to small vessels more
      closely tied to the sites of neural activity. Such an improved functional
      localization, however, has not yet been demonstrated at the cortical level in
      humans. Here, we investigate the cortical depth dependence and neuronal
      specificity of the functional ADC contrast in the human primary visual cortex by
      performing high-resolution BOLD and ADC imaging during visual stimulation at 4 T.
      Our results show that, by using optimal parameters, the functional ADC changes
      are significantly higher in the middle cortical layers, whereas the BOLD signal
      changes are higher at the cortical surface and vary much less significantly
      across the cortex. These results are in good agreement with previous studies
      performed in anesthetized cats at 9.4 T and demonstrate the improved spatial
      specificity of the functional ADC contrast as compared to the BOLD contrast.

PMID- 19379818
TI  - Response of the somatotropic axis to alterations in feed intake of channel
      catfish (Ictaluruspunctatus).
AB  - To better understand the effects of reduced feeding frequency on the GH-IGF-I
      axis, channel catfish (Ictaluruspunctatus), were either fed (Fed control,
      commercial diet fed daily), fed every other day (FEOD, commercial diet fed every
      other day), or not fed (Unfed, no feed). Pituitary GH mRNA increased whereas
      hepatic growth hormone receptor (GHR), IGF-I mRNA, and plasma IGF-I decreased in
      the FEOD and Unfed fish (P<0.05). In another study, fish were either continually
      fed (Fed) or fasted and then re-fed (Restricted) to examine the physiological
      regulation of somatostatin-14 (SS-14) and SS-22 mRNA. Fasting increased (P<0.05)
      levels of SS-14 mRNA in the hypothalamus and pancreatic islets (Brockmann bodies)
      at d 30 while re-feeding decreased SS-14 mRNA to control values in all tissues
      examined by d 45. Fasting had no effect on levels of SS-22 mRNA in the pancreatic
      islets whereas SS-22 mRNA was not detected in the stomach or hypothalamus. The
      results demonstrate that feeding every other day has similar negative impacts on
      components of the GH-IGF-I axis as fasting. The observed increase in SS-14 mRNA
      in the hypothalamus and pancreatic islets suggests a role for SS-14 in modulating
      the GH-IGF-I axis in channel catfish.

PMID- 19379819
TI  - Two highly diverged New World Artemia species, A. franciscana and A. persimilis,
      from contrasting hypersaline habitats express a conserved stress protein
      complement.
AB  - The brine shrimp Artemia is a well known animal extremophile adapted to survive
      in very harsh hypersaline environments. We compared the small stress proteins
      artemin and p26, and the chaperone hsc70 in encysted embryos (cysts) of the New
      World species, A. franciscana and A. persimilis. Cysts of the former, from San
      Francisco Bay, USA (SFB), were used essentially as a reference for these
      proteins, while both species were from locations in Chile where they occur in
      habitats at latitudinal extremes, the Atacama desert and Patagonia. These two
      species are phylogenetically distant, A. persimilis being closer to the Old World
      species, whilst A. franciscana is considered younger and undergoing evolutionary
      expansion. Using western blotting we found all three stress proteins in cysts
      from these five populations in substantial although variable amounts. The protein
      profiles revealed by Coomassie staining after electrophoresis (SDS-PAGE) were
      similar qualitatively, in spite of marked differences in the habitats from which
      these populations originated, and the long time since they diverged. We interpret
      these findings as further evidence for the adaptive importance of these three
      conserved proteins in coping with the variable, but severe stresses these
      encysted embryos endure.

PMID- 19379820
TI  - Ensemble modeling for strain development of L-lysine-producing Escherichia coli.
AB  - One of the main strategies to improve the production of relevant metabolites has
      been the manipulation of single or multiple key genes in the metabolic pathways.
      This kind of strategy requires several rounds of experiments to identify enzymes
      that impact either yield or productivity. The use of mathematical tools to
      facilitate this process is desirable. In this work, we apply the Ensemble
      Modeling (EM) framework, which uses phenotypic data (effects of enzyme
      overexpression or genetic knockouts on the steady-state production rate) to
      screen for potential models capable of describe existing data and thus gaining
      insight to improve strains for l-lysine production. Described herein is a
      strategy to generate a set of kinetic models that describe a set of enzyme
      overexpression phenotypes previously determined in an Escherichia coli strain
      that produces increased levels of l-lysine in an industrial laboratory. This
      final ensemble of models captures the kinetic characteristics of the cell through
      screening of phenotypes after sequential overexpression of enzymes. Furthermore,
      these models demonstrate some predictive capability, as starting from the
      reference producing strain (overexpressing desensitized dihydrodipicolinate
      synthetase (dapA*)) this set of models is able to predict that the
      desensitization of aspartate kinase (lysC*) is the next rate-controlling step in
      the l-lysine pathway. Moreover, this set of models allows for the generation of
      further targets for testing, for example, phosphoenolpyruvate (Ppc), aspartate
      aminotransferase (AspC), and glutamate dehydrogenase (GdhA). This work
      demonstrates the usefulness, applicability, and scope that the Ensemble Modeling
      framework offers to build production strains.

PMID- 19379821
TI  - Development of strains of the thermotolerant yeast Hansenula polymorpha capable
      of alcoholic fermentation of starch and xylan.
AB  - The thermotolerant yeast Hansenula polymorpha ferments glucose and xylose to
      ethanol at high temperatures. However, H. polymorpha cannot utilize starchy
      materials or xylans. Heterologous amylolytic and xylanolytic enzymes have to be
      expressed in this yeast to provide for utilization and growth on starch and
      xylan. Genes SWA2 and GAM1 from the yeast Schwanniomyces occidentalis, encoding
      alpha-amylase and glucoamylase, respectively, were expressed in H. polymorpha.
      The expression was achieved by integration of the SWA2 and GAM1 genes under the
      strong constitutive promoter of the H. polymorpha glyceraldehyde-3-phosphate
      dehydrogenase gene (HpGAP) into H. polymorpha genome. Resulting transformants
      acquired the ability to grow on a minimal medium containing soluble starch as a
      sole carbon source. Ethanol production at high-temperature fermentation from
      starch by the recombinant strains was up to 10 g/L. The XYN2 gene encoding
      endoxylanase of the fungus Trichoderma reseei was expressed in H. polymorpha. Co
      expression of xlnD gene coding for beta-xylosidase of the fungus Aspergillus
      niger and the XYN2 gene in H. polymorpha was achieved by integration of these
      genes under control of the HpGAP promoter. Resulting transformants were capable
      of growth and alcoholic fermentation on a minimal medium supplemented with
      birchwood xylan as a sole carbon source at 48 degrees C.

PMID- 19379822
TI  - Myelin, DIGs, and membrane rafts in the central nervous system.
AB  - Over the past 40 years our understanding of the organization of cell membranes
      has changed dramatically. Membranes are no longer viewed as a homogenous sea of
      phospholipids studded with randomly positioned islands of proteins. Our current
      view of the membrane involves the formation of small lipid clusters, comprised
      mainly of cholesterol and sphingolipids, known as membrane rafts. These lipid
      clusters apparently include and exclude specific proteins leading to the
      hypothesis that these domains (1) regulate cellular polarity and
      compartmentalization through trafficking and sorting, (2) provide platforms for
      cellular signaling and adhesion, and (3) function as cellular gate keepers.
      Tremendous controversy surrounds the concept of membrane rafts primarily because
      these small, highly dynamic entities are too small to be observed with
      traditional microscopic methods and the most utilized approach for raft analysis
      relies on poorly quantified, inconsistent biochemical extractions. New analytical
      approaches are being developed and applied to the study of membrane rafts and
      these techniques provide great promise for furthering our understanding of these
      enigmatic domains. In this review we will provide a brief summary of the current
      understanding of membrane rafts, utilizing the CNS myelin literature for
      illustrative purposes, and present caveats that should be considered when
      studying these domains.

PMID- 19379823
TI  - Orphan endogenous lipids and orphan GPCRs: a good match.
AB  - A large and growing family of over 70 endogenous lipids of the basic structure N
      acyl amide has been identified during the last 10 years. Only a few of these
      lipids have been characterized for biological activity, however, those that have
      shown a wide-range of activity may act at G-protein coupled receptors (GPCRs).
      Like orphan GPCRs that are identified as being in the genome and expressed in
      tissue, the majority of these endogenous lipids many produced throughout the
      body, some predominately in nervous tissue, remain orphaned. Here, we give a
      brief history of these orphan lipids and highlight the activity of N-arachidonoyl
      glycine, and farnesyl pyrophosphate at the orphan receptors GPR18 and GPR92,
      respectively, as well as summarizing the biological and pharmacological data for
      the recently identified N-palmitoyl glycine that suggests activity at a novel
      GPCR. Working to deorphanize both lipids and GPCRs together provides a unique
      opportunity for a greater understanding of cellular signaling and a challenge to
      find them all a home.

PMID- 19379824
TI  - Inhibition of the human neutrophil NADPH oxidase by Coxiella burnetii.
AB  - Coxiella burnetii is an obligate intracellular Gram-negative pathogen. A notable
      feature of C. burnetii is its ability to replicate within acidic phagolysosomes;
      however, the mechanisms utilized in evading host defenses are not well defined.
      Here, we investigated human neutrophil phagocytosis of C. burnetii (Nine Mile,
      phase II; NMII) and the effect of phagocytosed organisms on neutrophil reactive
      oxygen species (ROS) production. We found that opsonization with immune serum
      substantially enhanced phagocytosis of NMII. Human neutrophils phagocytosing
      opsonized NMII generated very little ROS compared to cells phagocytosing
      opsonized Staphylococcus aureus, Escherichia coli, or zymosan. However,
      phagocytosis of NMII did not affect the subsequent ROS response to a soluble
      agonist, indicating inhibition was localized to the phagolysosome and was not a
      global effect. Indeed, analysis of NADPH oxidase assembly in neutrophils after
      phagocytosis showed that translocation of cytosolic NADPH oxidase proteins,
      p47(phox) and p67(phox), to the membrane was absent in cells phagocytosing NMII,
      as compared to cells phagocytosing S. aureus or activated by phorbol myristate
      acetate. Thus, phagocytosed NMII is able to disrupt assembly of the human
      neutrophil NADPH oxidase, which represents a novel virulence mechanism for this
      organism and appears to be a common mechanism of virulence for many intracellular
      pathogens.

PMID- 19379826
TI  - Th17 cells.

PMID- 19379827
TI  - Study of the effects of a new pyrazolecarboxamide: changes in mitochondria and
      induction of apoptosis.
AB  - Drug resistance of cancer cells is often correlated with the evasion of
      apoptosis, thus a major goal in cancer research is to search for compounds able
      to counteract cancer by promoting apoptosis. A variety of compounds with
      anticancer activity are characterised by the presence of the pyrazole as core
      nucleus. We synthesised a panel of pyrrolyl-pyrazole-carboxamides and we focused
      on the new compound RS 2780 (N-2-phenylethyl 1-(4-chlorophenyl)-3-methyl-5
      pyrrolylpyrazole-4-carboxamide). The biological effects of RS 2780 on cell
      proliferation and viability were first evaluated on human HeLa cancer cells. As
      revealed by cell growth and viability experiments, a 24-h treatment of HeLa cells
      with increasing concentrations of RS 2780 (ranging from 0.1 to 100 microM) proved
      to inhibit cell proliferation and to affect cell viability. Notably, the new
      compound was effective also on colon carcinoma SW613-B3 cells, which are
      extremely resistant to most drugs, while it does not alter the proliferation of
      normal fibroblasts. We observed that RS 2780 interferes with the structural and
      functional properties of mitochondria, leading to the activation of the
      mitochondria-dependent apoptotic pathway. Apoptosis occurrence was supported by a
      number of morphological and biochemical hallmarks, including chromatin
      condensation, internucleosomal DNA fragmentation, PARP-1 cleavage and caspase
      activation. In conclusion, our results demonstrate for the first time the
      antiproliferative properties of the new compound RS 2780 on HeLa and SW613-B3
      cancer cells and show that its effects on mitochondria lead to apoptosis.

PMID- 19379825
TI  - Signal transduction and Th17 cell differentiation.
AB  - The paradigm of effector T helper cell differentiation into either Th1 or Th2
      lineages has been notably shaken by the discovery of a third lineage of cells
      that selectively produce interleukin (IL)-17. Characterization of this new
      subset, referred to as Th17, has provided exciting new insights into
      immunoregulation, host defense and the pathogenesis of autoimmune diseases.
      Additionally, the discovery of this T cell subset has offered a fresh look at
      such concepts as lineage commitment and terminal differentiation. The
      transcriptional regulatory events and epigenetic modifications that control these
      processes are diverse and complex, and despite the rapid pace at which data
      continue to accumulate, many questions remain to be answered. Here we review our
      current understanding of the signaling pathways, molecular interactions and
      transcriptional events that lead to Th17 differentiation and effector function,
      as well as the epigenetic modifications that accompany them.

PMID- 19379828
TI  - Particularities of mitochondrial structure in parasitic protists (Apicomplexa and
      Kinetoplastida).
AB  - Without mitochondria, eukaryotic cells would depend entirely on anaerobic
      glycolysis for ATP generation. This also holds true for protists, both free
      living and parasitic. Parasitic protists include agents of human and animal
      diseases that have a huge impact on world populations. In the phylum Apicomplexa,
      several species of Plasmodium cause malaria, whereas Toxoplasma gondii is a
      cosmopolite parasite found on all continents. Flagellates of the order
      Kinetoplastida include the genera Leishmania and Trypanosoma causative agents of
      human leishmaniasis and (depending on the species) African trypanosomiasis and
      Chagas disease. Although clearly distinct in many aspects, the members of these
      two groups bear a single and usually well developed mitochondrion. The single
      mitochondrion of Apicomplexa has a dense matrix and many cristae with a circular
      profile. The organelle is even more peculiar in the order Kinetoplastida,
      exhibiting a condensed network of DNA at a specific position, always close to the
      flagellar basal body. This arrangement is known as Kinetoplast and the name of
      the order derived from it. Kinetoplastids also bear glycosomes, peroxisomes that
      concentrate enzymes of the glycolytic cycle. Mitochondrial volume and activity is
      maximum when glycosomal is low and vice versa. In both Apicomplexa and
      trypanosomatids, mitochondria show particularities that are absent in other
      eukaryotic organisms. These peculiar features make them an attractive target for
      therapeutic drugs for the diseases they cause.

PMID- 19379829
TI  - Complexity of mitochondrial dynamics in neurons and its control by ADP produced
      during synaptic activity.
AB  - This review focuses on different aspects of dynamics of mitochondria in neuronal
      cytoplasm which play an important role in the life and fate of neurons. It starts
      with description of the energy supply in the brain; considers the typical
      patterns of mitochondrial movements; relates them to the neuronal activity and in
      particular at the synapses; extends to the analysis of the origin of local ATP
      changes in the cytoplasm; considers main features of motor-assisted movements of
      mitochondria and their role in determining a transport velocity; describes the
      measurements of ATP gradients in neuronal processes and relates them to spatial
      variations in the mobility of mitochondria that occur in the vicinity of synapses
      due to the local ADP increases; considers the influence of hypoxia and
      intracellular signalling pathways on mitochondria movements. Finally, the recent
      views on the mechanisms and possible functional role of mitochondrial network as
      a whole in neurons are discussed and unresolved issues and future perspectives in
      this field of research are delineated.

PMID- 19379830
TI  - Immunoinformatics: current trends and future directions.
AB  - Immunoinformatics has recently emerged as a critical field for accelerating
      immunology research. Although still an evolving process, computational models now
      play instrumental roles, not only in directing the selection of key experiments,
      but also in the formulation of new testable hypotheses through detailed analysis
      of complex immunologic data that could not be achieved using traditional
      approaches alone. Immunomics, which combines traditional immunology with computer
      science, mathematics, chemistry, biochemistry, genomics and proteomics for the
      large-scale analysis of immune system function, offers new opportunities for
      future bench-to-bedside research. In this article, we review the latest trends
      and future directions of the field.

PMID- 19379831
TI  - The corticotropin-releasing factor system in inflammatory bowel disease:
      prospects for new therapeutic approaches.
AB  - Mounting evidence suggests that stress is implicated in the development of
      inflammatory bowel disease (IBD), via initial nervous disturbance and subsequent
      immune dysfunction through brain-gut interactions. The corticotropin-releasing
      factor (CRF) system, being the principal neuroendocrine coordinator of stress
      responses, is involved in the inflammatory process within the gastrointestinal
      tract, via vagal and peripheral pathways, as implied by multiple reports reviewed
      here. Blocking of CRF receptors could theoretically exert beneficial anti
      inflammatory effects in colonic tissues. The recently synthesised small-molecule
      CRF(1) antagonists or alternatively non-peptide CRF(2) antagonists when
      available, may become new reliable options in the treatment of IBD.

PMID- 19379833
TI  - How to assess the mutagenic potential of cosmetic products without animal tests?
AB  - Animal experiments (in vivo tests) currently play a key role in genotoxicity
      testing. Results from in vivo tests are, in many cases, decisive for the
      assessment of a mutagenic potential of a test compound. The Seventh Amendment to
      the European Cosmetics Directive will, however, ban the European marketing of
      cosmetic/personal care products that contain ingredients that have been tested in
      animal experiments. If genotoxicity testing is solely based on the currently
      established in vitro tests, the attrition rate for chemicals used in cosmetic
      products will greatly increase due to irrelevant positive in vitro test results.
      There is urgent need for new and/or improved in vitro genotoxicity tests and for
      modified test strategies. Test strategies should consider all available
      information on chemistry of the test substance/the chemical class (e.g. SAR,
      metabolic activation and dermal adsorption). Test protocols for in vitro
      genotoxicity tests should be sensitive and robust enough to ensure that negative
      results can be accepted with confidence. It should be excluded that positive in
      vitro test results are due to high cytotoxicity or secondary genotoxic effects
      which may be thresholded and/or only occur under in vitro test conditions.
      Consequently, further research is needed to establish the nature of thresholds in
      in vitro assays and to determine the potential for incorporation of mode of
      action data into future risk assessments. New/improved tests have to be
      established and validated, considering the use of (metabolically competent)
      primary (skin) cells, 3D skin models and cells with defined capacity for
      metabolic activation (e.g. genetically engineered cell lines). The sensitivity
      and specificity of new and improved genotoxicity tests has to be determined by
      testing a battery of genotoxic and non-genotoxic chemicals. New or adapted
      international guidelines will be needed for these tests. The establishment of
      such a new genotoxicity testing strategy will take time and the new in vitro
      genotoxicity testing will become much more complex and will require greater
      mechanistic understanding to build a weight of evidence decision, which will be
      demanding and time-consuming. At present, no validated alternative methods for
      the follow-up of positive results from the standard genotoxicity battery are
      available and an appropriate evaluation of the mutagenic potential of cosmetic
      ingredients without animal experiments is therefore not possible in many cases.

PMID- 19379832
TI  - Piplartine induces genotoxicity in eukaryotic but not in prokaryotic model
      systems.
AB  - Piplartine {5,6-dihydro-1-[(2E)-1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propen-1-yl]
      2(1H)-pyridinone} is an alkamide present in Piper species that exhibits promising
      anticancer properties. It was previously shown that piplartine is mutagenic in
      yeast and cultured mammalian cells. This study was performed to increase the
      knowledge on the mutagenic potential of piplartine using the Salmonella/microsome
      assay, V79 cell micronucleus and chromosome aberration assays, and mouse bone
      marrow micronucleus tests. Piplartine was isolated from the roots of Piper
      tuberculatum. This extracted compound was unable to induce a mutagenic response
      in any Salmonella typhimurium strain either in the presence or absence of
      metabolic activation. Piplartine showed mutagenic effects in V79 cells, as there
      was an increased frequency of aberrant cells and micronuclei formation. In
      addition, piplartine administered at 50mg/kg did not induce micronucleus
      formation in vivo, but a dose of 100mg/kg induced an increase in the levels of
      micronucleus polychromatic erythrocytes (MNPCEs). Overall, these results provide
      further support that piplartine induces in vivo and in vitro mutagenicity in
      eukaryotic models.

PMID- 19379834
TI  - Morphological comparison of Lophotaspis from freshwater mollusks and turtles in
      Japan and China, with the correction of original description of Lophotaspis
      orientalis Faust and Tang, 1936 (Aspidogastrea: Aspidogasteridae).
AB  - The morphology of a type specimen of Lophotaspis orientalis Faust and Tang, 1936
      (Aspidogastrea: Aspidogasteridae) was compared with the morphology of the
      original description of L. corbiculae Moriya, 1944 and of newly collected
      specimens from Corbicula species in China and Japan. The original description of
      L. orientalis was revised by the re-examination of the type specimen.
      Consequently, some key characteristics of these two species described by Moriya
      (1944) became invalid. The gonad size of the L. orientalis type specimen was out
      of the range of all other investigated specimens and past records, suggesting
      that the L. orientalis type specimen (host: soft-shell turtle) is a different
      species from the other investigated specimens (host: freshwater clam).

PMID- 19379835
TI  - Effect of oxcarbazepine on sleep architecture.
AB  - The most common side effects following administration of antiepileptic drugs
      involve alterations in sleep architecture and varying degrees of daytime
      sleepiness. Oxcarbazepine is a drug that is approved as monotherapy for the
      treatment of partial seizures and generalized tonic-clonic seizures. However,
      there is no information about its effects on sleep pattern organization;
      therefore, the objective of this work was to analyze such effects. Animals
      (Wistar rats) exhibited three different behavioral and electrophysiological
      states of vigilance: wakefulness, slow wave sleep (SWS), and rapid eye movement
      (REM) sleep. Oral treatment with oxcarbazepine (100 mg/kg) produced an increment
      in total sleep time throughout the recording period. This increment involved both
      SWS and REM sleep. Mean duration of the REM sleep phase was not affected. In
      contrast, the frequency of this sleep phase increased significantly across the 10
      hour period. REM sleep latency shortened significantly. Results obtained in this
      work indicate that oxcarbazepine's acute effects point to hypnotic properties.

PMID- 19379836
TI  - Executive dysfunction in children and adolescents with temporal lobe epilepsy: is
      the Wisconsin Card Sorting Test enough?
AB  - The Wisconsin Card Sorting Test (WCST) is the gold standard in the evaluation of
      executive dysfunction (ED) in patients with temporal lobe epilepsy (TLE). We
      evaluated 35 children with TLE and 25 healthy controls with the WCST and with a
      more comprehensive battery. Among the children with TLE, 77.14% showed impairment
      on the WCST. On other tests (Wechsler Intelligence Scale for Children-Digit
      Forward, Matching Familiar Figures Test, Trail Making Test, Word Fluency, Finger
      Windows, and Number-Letter Memory), impairment was demonstrated in 94.29%. The
      authors concluded that the WCST is a good paradigm to measure executive
      impairment in children with TLE; however, it may be not enough. Evaluation
      performed only with the WCST not only underestimated the number of patients with
      ED, but also missed relevant information regarding the type of ED.

PMID- 19379837
TI  - Purification of peptides with differential cytolytic activities from the skin
      secretions of the Central American frog, Lithobates vaillanti (Ranidae).
AB  - Peptide-based defenses of ranid frogs from Mexico and Central America have been
      studied in much less detail than those from North America. Peptides belonging to
      the brevinin-1 (5 peptides), palustrin-2 (1 peptide), and ranatuerin-2 (3
      peptides) families were isolated from norepinephrine-stimulated skin secretions
      of the Costa Rican frog, Lithobates vaillanti (Ranidae) and characterized
      structurally. Brevinin-1VLa (FLGAIAGVAAKFLPKVFCFITKKC) and brevinin-1VLc
      (FLPVIASVAAKVLPK VFCFITKKC) showed particularly high growth-inhibitory potency
      (MIC < or =3 microM) against a Gram-positive microorganism Staphylococcus aureus
      and the opportunistic yeast pathogen Candida albicans and potent cytolytic
      activity (LC(50)< or =8 microM) against both human erythrocytes and HepG2
      hepatoma-derived cells. The peptides were also active against a Gram-negative
      microorganism Escherichia coli (MIC< or =50 microM). Substitutions in brevinin
      1VLd (Lys(11) --> Asn) and brevinin-1VLe (Lys(11) --> Ser) that decrease
      cationicity result in loss of activity against E. coli. Ranatuerin-2VLb
      (GIMDTIKGAAKDLAGQLLDKLKCKITKC) showed relatively weak antimicrobial activity
      (MIC> or =75 microM) but selective cytolytic activity against HepG2 tumor cells
      (LC(50)=30 microM) compared with erythrocytes (LC(50)>200 microM). In addition, a
      dodecapeptide (RICYAMWIPYPC) were isolated from the secretions that were devoid
      of antimicrobial activity. This component contains an Ala-Met bond that
      constitutes the scissile bond in the selective elastase inhibitor, elafin but the
      peptide did not inhibit pancreatic elastase at concentrations up to 100 microM.

PMID- 19379838
TI  - Effects of environmental relevant doses of pollutants from offshore oil
      production on Atlantic cod (Gadus morhua).
AB  - The release of produced water (PW), a by-product of offshore oil production, has
      increased in Norwegian waters in recent years. Alkylphenols (AP), a major
      component of PW, have been shown to have endocrine disrupting effects on several
      fish species. In the present study, four groups of female Atlantic cod (Gadus
      morhua) were orally exposed for 20 weeks to two different concentrations of a
      mixture of C4-C7 APs, PW or 17beta-estradiol. The transcriptional responses in
      the liver of Atlantic female cod were studied using a custom-made cDNA
      microarray. The largest transcriptional effects were seen in cod exposed to the
      lowest dose of APs. Several biological processes such as glycolysis, apoptosis
      and the general stress response were affected by exposure to APs. In addition,
      genes coding for the detoxification enzymes CYP1A and sulfotransferase 2 were up
      regulated in the low exposure group. Significant reduction in gonadosomatic index
      (GSI) and the concentration of plasma vitellogenin were seen in both AP and
      17beta-estradiol exposed cod. Exposure to PW had little effect on GSI and the
      regulation of stress responsive genes. The findings indicate that chronic
      exposure to low levels of APs may cause a stress response and delayed maturation
      in female cod.

PMID- 19379839
TI  - Distinct expression of two foxg1 paralogues in zebrafish.
AB  - The forkhead proteins (Fox) act as transcription factors in many biological
      processes in a wide range of species. One member of this superfamily, Foxg1, has
      essential roles in the development of eyes, telencephalon, ears and olfactory
      system. Zebrafish foxg1 has been reported to have similar roles as the mouse
      orthologue Foxg1. However, no data has been reported about possible zebrafish
      foxg1 paralogues. In this study we identified one zebrafish foxg1 paralogue by
      enhancer trapping, which we designate foxg1b. A more diverged paralogue, foxg1c,
      was identified by homology searches. Sequence comparisons indicate that both
      foxg1b and foxg1c are less related to mouse than the previously characterized
      foxg1. We report that foxg1b is expressed in a regionally restricted pattern
      within the developing eye, mainly in the dorsal-nasal retina, which is similar to
      the retinal expression of mouse Foxg1. By contrast, foxg1c is only expressed
      transiently in the eyes and forebrain between 14 and 20h post-fertilization,
      while expression was detected exclusively in the developing inner ear at later
      stages. Our results suggest that foxg1b and foxg1c have undergone expression
      pattern divergence during evolution that has resulted in functional
      specialization.

PMID- 19379840
TI  - Phylogenetics, evolution, and medical importance of polyomaviruses.
AB  - The increasing frequency of tissue transplantation, recent progress in the
      development and application of immunomodulators, and the depressingly high number
      of AIDS patients worldwide have placed human polyomaviruses, a group of pathogens
      that can become reactivated under the status of immunosuppression, suddenly in
      the spotlight. Since the first description of a polyomavirus a half-century ago
      in 1953, a multiplicity of human and animal polyomaviruses have been discovered.
      After reviewing the history of research into this group, with a special focus is
      made on the clinical importance of human polyomaviruses, we conclude by
      elucidating the phylogenetic relationships and thus evolutionary history of these
      viruses. Our phylogenetic analyses are based on all available putative
      polyomavirus species as well as including all subtypes, subgroups, and
      (sub)lineages of the human BK and JC polyomaviruses. Finally, we reveal that the
      hypothesis of a strict codivergence of polyomaviruses with their respective hosts
      does not represent a realistic assumption in light of phylogenetic findings
      presented here.

PMID- 19379841
TI  - Water-borne transmission drives avian influenza dynamics in wild birds: the case
      of the 2005-2006 epidemics in the Camargue area.
AB  - Transmission and persistence of avian influenza viruses (AIV) among wildlife
      remains an unresolved issue because it depends both on the ecology of the host
      (e.g. population density, migration) and on the environment (e.g. AIV persistence
      in water). We have developed a mathematical model that accounts for both AIV
      epidemics and bird community dynamics. The model is parameterized using bird
      counts and AIV prevalence data. Results suggest that the transmission patterns
      driving the dynamics of infection at our study site (Camargue, South of France)
      involved both a density-dependent and a water-borne transmission processes. Water
      borne transmission is, however, the main determinant of the disease dynamics and
      observed prevalence level. This pattern of transmission highlights the importance
      of the persistence of viral particles in water in AIV dynamics in wild birds.

PMID- 19379842
TI  - Population genetic tests suggest that the epidemiologies of JCV and BKV are
      strikingly different.
AB  - The JCV and BKV viruses have been used as markers for the study of human
      evolution by assuming that these viruses coevolved with their host. However, it
      is currently unclear whether the details of the population expansion of these
      viruses and humans agree. To study this in more detail, large numbers of complete
      genomes were used for population genetic tests to detect evidence for population
      expansion. Relative to the neutral expectation of no selective forces and no
      demographic changes, the JCV data set contained a striking excess of synonymous
      and non-synonymous mutations that occur only once in the data set. The same was
      found for non-synonymous mutations of BKV, but not at all for synonymous
      mutations of BKV. The different frequency spectra of mutations in JCV and BKV do
      not result from the inclusion of patients with clinical symptoms associated with
      BKV and JCV, such as nephropathy or progressive multifocal leucoencefalopathy,
      nor from the different numbers of genomes available for JCV and BKV. Instead, the
      distribution of unique mutations and population genetic models that use older
      mutation classes indicate a striking difference of the historical demographies of
      JCV and BKV with only the former virus exhibiting the evidence of demographic
      expansion. Our analyses expand on recent population genetic analyses that
      document a global population expansion of JCV by taking into account the impact
      of deleterious mutations and by comparing both human viruses. The striking
      difference between the demographics of BKV and JCV suggests that important
      aspects of their epidemiology remain to be discovered.

PMID- 19379843
TI  - Distinct haplotypes of dhfr and dhps among Plasmodium falciparum isolates in an
      area of high level of sulfadoxine-pyrimethamine (SP) resistance in eastern Sudan.
AB  - Typing of polymorphic microsatellites that are linked to drug resistance genes
      has shed light on the origin and pattern of spread of some anti-malarial drugs.
      Recent surveys revealed spread of a high-level pyrimethemine resistant lineage of
      Plasmodium falciparum, of Asian origin, across Africa. Here, we examined
      mutations in dihydrofolate reductase, dhfr [chromsosome 4], the dihydropteroate
      synthase, dhps [chromosome 8] associated with resistance to sulfadoxine
      pyrimethamine (SP), and neighboring microsatellites among P. falciparum isolates
      in Asar village, eastern Sudan. This area lies at the fringes of malaria
      endemicity, where the remote P. falciparum parasites have some distinct genetic
      characteristics. Overall, 89% (84/94) of the examined isolates carried double
      mutations at dhfr (N51I and S108N), but the 59R and I164L mutations were not
      seen. Similarly, the majority, 43% (35/81) of the isolates carried double
      mutations at dhps (437G, 540E). Analysis of neighboring microsatellites revealed
      one major dhfr haplotype with mutations (51I, 108N) and one dhps haplotype with
      mutations (436S, 437G, 540E). These haplotypes differ from the major ones thought
      to drive resistance to SP across Africa. The resistant haplotypes of dhfr and
      dhps, in Asar, share some microsatellites with the wild genotypes suggesting that
      they were generated locally. Among isolates successfully examined, 40% shared
      identical haplotypes of the 2 loci, comprising a dominant resistant lineage.
      Undoubtedly, this lineage plays an important role in clinical failure to SP in
      this area.

PMID- 19379844
TI  - Neural autonomic control in orthostatic intolerance.
AB  - Inability to maintain the upright position is manifested by a number of symptoms
      shared by either human pathophysiology and conditions following weightlessness or
      bed rest. Alterations of the neural sympathetic cardiovascular control have been
      suggested to be one of the potential underlying etiopathogenetic mechanisms in
      these conditions. We hypothesize that the study of the autonomic profile of human
      orthostatic intolerance syndromes may furnish a valuable insight into the
      complexity of the sympathetic alterations leading to a reduced gravitational
      tolerance. In the present paper we describe abnormalities both in the magnitude
      and in the pattern of the sympathetic neural firing observed in patients affected
      by orthostatic intolerance, attending the upright position. Also, we discuss
      similarity and differences in the neural sympathetic mechanisms regulating the
      cardiovascular system during the gravitational stimulus both in clinical
      syndromes and in subjects returning from space.

PMID- 19379845
TI  - Cardiovascular deconditioning: From autonomic nervous system to microvascular
      dysfunctions.
AB  - Weightlessness induces an acute syndrome called the cardiovascular
      deconditioning, associating orthostatic intolerance with syncope, increase in
      resting heart rate and decrease in physical capability. Orthostatic intolerance
      occurs after short term and long term head down bed rest and after long term
      space flight. Both head down bed rest and space flight induce a significant
      decrease of the spontaneous baroreflex sensitivity. However, spontaneous
      baroreflex sensitivity only characterizes the cardiac baroreflex loop. To go
      further with the analysis of cardiovascular deconditioning we were interested in
      the microcirculation. As the endothelium plays a crucial role in the regulation
      of vascular homeostasis and local blood flow, we hypothesized that endothelial
      dysfunction is associated with bed rest induced changes. We investigated
      endothelial properties before and after 56 days of bed rest in 8 women of control
      group and in 8 women who regularly performed physical exercise as countermeasure.
      Our study shows that prolonged bed rest causes impairment of endothelium
      dependent functions at the microcirculation level, along with an increase in
      circulating endothelial cells. Endothelium should be a target for countermeasures
      during periods of prolonged bed rest or exposure to weightlessness.

PMID- 19379846
TI  - Cardio-postural deconditioning: A model for post-flight orthostatic intolerance.
AB  - Post-flight astronauts experience temporary but sometimes severe postural control
      dysfunction and decreased orthostatic tolerance. Research points to a possible
      link between cardiovascular and postural controls and orthostatic tolerance
      [Claydon,V.E., Hainsworth, R., 2006. Postural sway in patients with syncope and
      poor orthostatic tolerance. Heart 92, 1688-1689], for which a neurophysiological
      model has been presented [Souvestre, P.A., Blaber A.P., Landrock C.K., 2008.
      Space motion sickness: the sensory-motor controls and cardiovascular correlation.
      Acta Astronautica 63, 745-757]. To validate this model, young and elderly
      subjects (n=12) were compared with respect to postural mediolateral sway (ML
      sway) and blood pressure (BP) during quiet standing. Both groups had a peak in
      the low frequency region (0.03-0.07Hz) of cross-spectral power between ML sway
      and BP; however, only the young subjects had signal coherence greater than 0.5.
      Short-range Hurst coefficient from Stabilogram Dynamic Analysis was significantly
      lower for ML sway in young (0.694+/-0.068) compared to elderly subjects (0.812+/
      0.10) (p=0.028). Young subjects were better able to command a closed-loop
      strategy of motor-control providing a more efficient postural control. Further
      application of this model with astronauts could lead to further understanding of
      post-flight orthostatic intolerance.

PMID- 19379847
TI  - Characterization of a de novo balanced translocation in a patient with moderate
      mental retardation and dysmorphic features.
AB  - Moderate mental retardation (MR) could affect up to 3% of the general population.
      A proportion of these cases has a genetic origin. Genes responsible for mental
      retardation can be identified taking advantage of familial cases or patients
      carrying a chromosomal rearrangement. We have studied a female patient with mild
      mental retardation and dysmorphic features. Cytogenetic and molecular
      investigations revealed a de novo balanced translocation 46, XX,
      t(5;18)(q21.3;q21.32) in the patient. The karyotypes of the parents are normal.
      We mapped the breakpoints of the translocation on chromosomes 5 and 18 by
      fluorescence in situ hybridization (FISH). The characterization of the
      chromosomal breakpoints helped us identify a new candidate region containing a
      portion of a gene. This gene is called FER. It is a tyrosine kinase located on
      the chromosome 5q21.3. We found no known genes in the genomic region
      corresponding to the BAC spanning the 18q21.32 breakpoint. Molecular analysis
      showed that the FER gene was not interrupted by the translocation breakpoint on
      chromosome 5. Real-time quantitative PCR performed using RNA from the patient,
      compared to her parents and controls, showed no significant modification of FER
      expression ruling out a putative position effect, at least in the tissue tested.
      Our data suggest that FER is not implicated in the mental retardation phenotype
      observed in the reported patient. Therefore the MR phenotype might not be caused
      by the translocation.

PMID- 19379848
TI  - Cortical bone mineralization differences between hip-fractured females and
      controls. A microradiographic study.
AB  - The strength of bone depends on both bone quantity and bone quality. One
      determinant of bone quality is the degree of mineralization of bone tissue (DMB).
      To assess the role for DMB in osteoporotic hip fractures, we compared the degree
      of mineralization in femoral neck cortex from 23 women with hip fractures (age,
      65-96 years) and 14 female controls (age, 75-103 years) using quantitative
      microradiography calibrated with an aluminum step wedge. Variables were DMB in
      osteons (oDMB(Al)mean) and interstitial tissue (exDMB(Al)mean). Wilcoxon signed
      rank tests were used to compare oDMB(Al)mean to exDMB(Al)mean in each group, and
      Mann-Whitney tests to compare oDMB(Al)mean and exDMB(Al)mean between hip-fracture
      patients and controls. DMB was significantly lower in the osteons than in the
      interstitial tissue in both groups (hip-fracture group, P=0.000; control group,
      P=0.001). DMB values in osteons and interstitial tissue were significantly
      greater in the hip-fracture patients than in the controls (P=0.007 and P=0.005,
      respectively). These cross-sectional data suggest that bone fragility may be
      related to a higher degree of tissue mineralization.

PMID- 19379850
TI  - Treatment of a recurrent aneurysmal bone cyst with bioactive glass in a child
      allows for good bone remodelling and growth.
AB  - A recurrent aneurysmal bone cyst of the proximal phalanx of the index finger of a
      three-year-old child, treated with bioactive glass, is presented. Over a two-year
      follow-up, the treated area appeared dense on X-rays. At two years, no cavity was
      observed and the homogenous region resembled normal trabecular bone. The phalanx
      had grown in length and remodelled to an almost normal shape.

PMID- 19379849
TI  - Contributions of trabecular rods of various orientations in determining the
      elastic properties of human vertebral trabecular bone.
AB  - Trabecular bone networks consist of two basic microstructural types: plates and
      rods. Although trabecular rods represent only a small fraction of total bone
      volume, their existence has important roles in failure initiation and
      progression. The goal of this study was to quantitatively examine the
      contributions of trabecular rods in various orientations to the anisotropic
      elastic moduli of human vertebral trabecular bone. Twenty-one human vertebral
      trabecular bone specimens were scanned by microcomputed tomography (microCT). A
      coordinate system of orthotropic axes representing the best elastic orthotropic
      symmetry was determined for each sample. Individual trabeculae segmentation
      (ITS), a 3D image analysis technique, was performed to identify each individual
      trabecular rod and determine its orientation in the orthotropic coordinate
      system. Next, three rod-removed images were created where longitudinal, oblique,
      or transverse trabecular rods were removed, respectively, from the original
      microCT images. The original and three categories of rod-removed images were then
      converted to finite element (FE) models for evaluation of their elastic moduli
      and anisotropy. Both the transverse and oblique rod-removal caused significant
      decreases in all six elastic moduli. However, the removal of longitudinal rods
      only caused significant changes in E(33), G(23), and G(31) but not in any
      transverse/in-plane elastic properties (E(11), E(22), and G(12)). The analysis of
      covariance (ANCOVA) with repeated measures was applied to detect the moduli
      change in the different models caused by the effects beyond just bone volume
      loss. The results suggested that the loss of transverse rods induced a
      significant decrease in in-plane mechanical competence, which was greater than
      what could be explained only by the associated bone volume loss. In contrast, the
      reduction in the axial Young's modulus caused by the loss of transverse rods was
      proportional to the bone volume decrease. Furthermore, the loss of longitudinal
      rods affected the axial Young's modulus through both bone volume loss and
      architectural change. With aging, the reduction in in-plane mechanical competence
      would be magnified by the preferential loss of transverse rods. The predictive
      ability of bone mineral density, a surrogate of BV/TV in clinical measurements,
      may reduce more quickly for transverse mechanical properties than for the axial
      mechanical properties.

PMID- 19379852
TI  - Use of initial biventricular mechanical support in a case of postinfarction
      ventricular septal rupture as a bridge to surgery.
AB  - The incidence of postinfarction ventricular septal rupture is declining as
      coronary revascularization techniques have become available for a large number of
      patients. However, morbidity and mortality rates associated with this
      complication remain high. We report the case of a patient suffering from acute
      myocardial infarction who developed a postinfarction ventricular septal defect.
      Instead of attempting surgical closure, he was placed on biventricular mechanical
      support. After 2 weeks, surgical closure of the defect and concomitant
      explantation of the assist device were successfully performed. This approach may
      represent a new treatment option restoring hemodynamic stability and avoiding
      surgery on freshly infarcted myocardium.

PMID- 19379851
TI  - Substance P stimulates bone marrow stromal cell osteogenic activity, osteoclast
      differentiation, and resorption activity in vitro.
AB  - INTRODUCTION: SP is a neuropeptide distributed in the sensory nerve fibers that
      innervate the medullar tissues of bone, as well as the periosteum. Previously we
      demonstrated that inhibition of neuropeptide signaling after capsaicin treatment
      resulted in a loss of bone mass and we hypothesized that SP contributes to bone
      integrity by stimulating osteogenesis. MATERIALS AND METHODS: Osteoblast
      precursors (bone marrow stromal cells, BMSCs) and osteoclast precursors (bone
      marrow macrophages, BMMs) derived from C57BL/6 mice were cultured. Expression of
      the SP receptor (NK1) was detected by using immunocytochemical staining and PCR.
      Effects of SP on proliferation and differentiation of BMSCs were studied by
      measuring BrdU incorporation, gene expression, alkaline phosphatase activity, and
      osteocalcin and Runx2 protein levels with EIA and western blot assays,
      respectively. Effects of SP on BMMs were determined using a BrdU assay, counting
      multinucleated cells staining positive for tartrate-resistant acid phosphatase
      (TRAP(+)), measuring pit erosion area, and evaluating RANKL protein production
      and NF-kappaB activity with ELISA and western blot. RESULTS: The NK1 receptor was
      expressed in both BMSCs and BMMs. SP stimulated the proliferation of BMSCs in a
      concentration-dependent manner. Low concentrations (10(-12) M) of SP stimulated
      alkaline phosphatase and osteocalcin expression, increased alkaline phosphatase
      activity, and up-regulated Runx2 protein levels, and higher concentrations of SP
      (10(-8) M) enhanced mineralization in differentiated BMSCs. SP also stimulated
      BMSCs to produce RANKL, but at concentrations too low to evoke osteoclastogenesis
      in co-culture with macrophages in the presence of SP. SP also activated NF-kappaB
      in BMMs and directly facilitate RANKL-induced macrophage osteoclastogenesis and
      bone resorption activity. CONCLUSIONS: NK1 receptors are expressed by osteoblast
      and osteoclast precursors and SP stimulates osteoblast and osteoclast
      differentiation and function in vitro. SP neurotransmitter release from sensory
      neurons could potentially regulate local bone turnover in vivo.

PMID- 19379853
TI  - Bailout after failed biventricular management of critical aortic stenosis:
      another application of the hybrid approach.
AB  - The decision between a single-ventricle and biventricular strategy can be
      particularly difficult in patients with critical left ventricular outflow
      obstruction who have marginal left ventricular size or function. Overzealous
      pursuit of a biventricular strategy in borderline cases can lead to death or
      require conversion to a single-ventricle physiology at increased risk. We
      describe novel use of the hybrid approach as a bailout option for a patient with
      critical aortic stenosis who, despite balloon valvuloplasty, exhibited persistent
      severe left ventricular dysfunction. This approach provides a simple and
      effective pathway to treat patients with a failed biventricular circulation, at a
      considerably lower risk, while keeping all therapeutic options open.

PMID- 19379854
TI  - Postpneumonectomy-like syndrome in an infant with right lung agenesis and left
      main bronchus hypoplasia.
AB  - We report a 1-year-old child born with agenesis of the right lung who sustained
      an episode of acute respiratory failure related to a postpneumonectomy-like
      syndrome, with severe mediastinal shift and subsequent stretching and stenosis of
      the left main bronchus. The insertion of an expandable prosthesis in the right
      empty pleural space markedly improved the patient's clinical condition.

PMID- 19379855
TI  - A novel titanium rib bridge system for chest wall reconstruction.
AB  - Chest wall resection for liposarcoma was performed. To reconstruct the chest wall
      we used a novel titanium rib bridge system and preserved anatomically equivalent
      layers.

PMID- 19379856
TI  - Immediate regression of thrombosed false lumen in ascending aorta of retrograde
      type A aortic dissection.

PMID- 19379857
TI  - Dual-source computed tomography assessment of malfunctioning mechanical
      prosthetic valve.

PMID- 19379858
TI  - Treatment selection for coronary artery disease: the collision of a belief system
      with evidence.

PMID- 19379859
TI  - Aortic dissection endovascular stenting: less pain, survival gain?

PMID- 19379860
TI  - Relations between cardiothoracic surgeons and industry.

PMID- 19379861
TI  - What is the value of a p value?
AB  - Successful publication of a research study usually requires a small p value,
      typically p < 0.05. Many clinicians believe that a p value represents the
      probability that the null hypothesis is true, so that a small p value means the
      null hypothesis must be false. In fact, the p value provides very weak evidence
      against the null hypothesis, and the probability that the null hypothesis is true
      is usually much greater than the p value would suggest. Moreover, even
      considering "the probability that the null hypothesis is true" is not possible
      with the usual statistical setup and requires a different (Bayesian) statistical
      approach. We describe the Bayesian approach using a well-established diagnostic
      testing analogy. Then, as a practical example, we compare the p-value result of a
      study of aprotinin-associated operative mortality with the more illuminative
      interpretation of the same study data using a Bayesian approach.

PMID- 19379863
TI  - Factors affecting interest in cardiothoracic surgery: survey of North American
      general surgery residents.
AB  - BACKGROUND: Applications to cardiothoracic surgery (CTS) training programs have
      declined precipitously. The viewpoints of potential applicants, general surgery
      residents, have not yet been assessed. Their perceptions are crucial to
      understanding the cause and formulating appropriate changes in our educational
      system. METHODS: An initial survey instrument was content-validated, and the
      final instrument was distributed electronically between March 24 and May 2, 2008
      through 251 general surgery program directors to all Accreditation Council for
      Graduate Medical Education-accredited general surgery residents (7,508). RESULTS:
      The response rate was 29% (2153 residents; 89% programs). Respondent's
      demographics matched existing data; 6% were committed to CTS, and 26% reported
      prior or current interest in CTS. Interest waned after postgraduate year 3.
      Interest correlated with CTS rotation duration. Of the respondents committed to
      CTS, 76% had mentors (71% were cardiothoracic surgeons). CTS had the most
      shortcomings among 9 subspecialties. Job security and availability accounted for
      46% of reported shortcomings (3 to 14 times higher than other subspecialties).
      Work schedule accounted for 25%. Length of training was not a very important
      factor, although it was identified as an option to increase interest in CTS.
      Residents who were undecided or uninterested in CTS were twice as likely to cite
      the ability to balance work and personal life as important than residents who
      chose CTS. CONCLUSIONS: The dominant concern documented in the survey is job
      security and availability. The importance of mentorship and exposure to CTS
      faculty in promoting interest was also evident. Decision makers should consider
      these findings when planning changes in education and the specialty.

PMID- 19379862
TI  - Aortic root replacement in 372 Marfan patients: evolution of operative repair
      over 30 years.
AB  - BACKGROUND: We reviewed the evolution of practice and late results of aortic root
      replacement (ARR) in Marfan syndrome patients at our institution. METHODS: A
      retrospective clinical review of Marfan patients undergoing ARR at our
      institution was performed. Follow-up data were obtained from hospital and office
      records and from telephone contact with patients or their physicians. RESULTS:
      Between September 1976 and September 2006, 372 Marfan syndrome patients underwent
      ARR: 269 had a Bentall composite graft, 85 had valve-sparing ARR, 16 had ARR with
      homografts, and 2 had ARR with porcine xenografts. In the first 24 years of the
      study, 85% received a Bentall graft; during the last 8 years, 61% had a valve
      sparing procedure. There was no operative or hospital mortality among the 327
      patients who underwent elective repair; there were 2 deaths among the 45 patients
      (4.4%) who underwent emergent or urgent operative repair. There were 74 late
      deaths (70 Bentalls, 2 homograft, and 2 valve-sparing ARRs). The most frequent
      causes of late death were dissection or rupture of the residual aorta (10 of 74)
      and arrhythmia (9 of 74). Of the 85 patients who had a valve-sparing procedure,
      40 had a David II remodeling operation; there was 1 late death in this group, and
      5 patients required late aortic valve replacement for aortic insufficiency. A
      David I reimplantation procedure using the De Paulis Valsalva graft has been used
      exclusively since May 2002. All 44 patients in this last group have 0 to 1+
      aortic insufficiency. CONCLUSIONS: Prophylactic surgical replacement of the
      ascending aorta in patients with Marfan syndrome has low operative risk and can
      prevent aortic catastrophe in most patients. Valve-sparing procedures,
      particularly using the reimplantation technique with the Valsalva graft, show
      promise but have not yet proven as durable as the Bentall.

PMID- 19379864
TI  - Endovascular treatment of type B aortic dissection: the challenge of late
      success.
AB  - BACKGROUND: Thoracic endovascular aortic repair of type B aortic dissection is a
      therapeutic option for selected patients. However, late outcomes of this
      intervention are virtually unknown, and the series already published are
      heterogenous regarding demographics, indications, and type of devices. METHODS:
      From 1997 to 2004, 106 patients exclusively with classic complicated or
      symptomatic type B aortic dissection were treated with thoracic endovascular
      aortic repair, using the same device. We present in-hospital outcomes and late
      follow-up for 73 patients. RESULTS: Technical success was achieved for 99% of
      patients, and the clinical success rate was 83% (exclusion of the false lumen, no
      early death or surgical conversion). In-hospital death occurred in 5 patients, 2
      of them after surgical conversion. Three patients required urgent surgical
      conversion. Neurologic complications occurred in 5 patients (1 case of
      paraplegia). The average time of follow-up was 35.9 +/- 28.5 months. During
      follow-up, 37% of patients initially successfully treated reached a failure
      criterion (new endovascular or surgical intervention in the same aortic segment
      or death due to aortic or unknown cause). Kaplan-Meier curve showed late survival
      rates higher than 80% in 2 years. CONCLUSIONS: Patients with both acute and
      chronic type B aortic dissection had excellent initial results with thoracic
      endovascular aortic repair. Although event-free survival rates decreased
      gradually with time owing to the frequent need for new interventions, survival
      curves were comparable to those for less complex patients undergoing clinical or
      surgical treatment. Randomized studies are required to establish the actual
      benefit of this new approach.

PMID- 19379865
TI  - Late outcomes of endovascular aortic repair for the infected thoracic aorta.
AB  - BACKGROUND: Untreated infectious thoracic aortic pathology (ITAP) has a dismal
      prognosis. Despite its high rates of morbidity in this setting, conventional open
      repair remains the gold standard therapy. Understanding the limitations of open
      repair, we describe outcomes for one of the largest series of ITAP treated with
      thoracic endovascular repair. METHODS: Of 170 patients undergoing thoracic
      endovascular repair (1993 to 2008), 20 presenting with ITAP were identified.
      Indications for intervention included aortobronchial (n = 10), aortoesophageal (n
      = 2), or aortocutaneous fistulae (n = 1), or mycotic aneurysms (n = 7).
      Underlying disease included fusiform aneurysm (n = 1), saccular aneurysm or
      pseudoaneurysm (n = 18), or dissection (n = 1). Four patients had ITAP from
      infected grafts. Follow-up was 100% complete (mean, 28.6 months). RESULTS: Median
      age was 73 years. A history of immunosuppression was present in 4; concurrent
      malignancy was present in 5. Arch repair was needed in 8; total descending, in 6.
      Three patients underwent hybrid thoracic endovascular repair or debranching
      procedures. Causes of in-hospital mortality (n = 3; 15.0%) included refractory
      hypoxemia (n = 1) and sepsis from tracheoesophageal fistula (n = 1) or pneumonia
      (n = 1). Dialysis was needed in 2; none sustained postoperative stroke or
      paraplegia. Mean Kaplan-Meier survival was 39.0 months. Late mortality was seen
      in 13 patients, with 3 attributed to recurrent ITAP. There was a trend for
      recurrence of ITAP when thoracic endovascular repair was originally performed in
      an infected graft (p = 0.08). At last imaging follow-up, 14 patients had a healed
      aorta. CONCLUSIONS: Treatment with thoracic endovascular repair for ITAP can be
      accomplished with acceptable results. Late mortality is frequently related to
      underlying comorbidities, rather than complications from the aortic disease
      itself, suggesting that thoracic endovascular repair is an appropriate palliative
      therapeutic option in this high-risk cohort.

PMID- 19379866
TI  - Augmentation index is elevated in aortic aneurysm and dissection.
AB  - BACKGROUND: The augmentation index, the ratio of the ejection pressure from the
      heart to the reflection pressure from the arterial system, has recently been
      recognized as one of the indexes of left ventricular afterload. We studied it in
      patients with aortic aneurysm and dissection, using carotid artery diameter
      waveform obtained from an echo-tracking system. METHODS: Forty-six patients were
      divided into the following three groups based on pathology: group A, 21 patients
      with thoracic aortic aneurysm; group B, 15 patients with chronic aortic
      dissection; and group C, 10 patients without any aortic diseases. Using an echo
      tracking system on the carotid artery, we measured stiffness parameter beta,
      arterial compliance, and the augmentation index. RESULTS: There was no
      significant difference in stiffness parameter beta and arterial compliance among
      the three groups. The augmentation index was significantly higher in groups A and
      B than group C (22 +/- 10%, 22 +/- 13% vs 8 +/- 17%; p = 0.012). Female (p =
      0.028) and heart rate (p = 0.005) were significantly associated with the
      augmentation index and the significance of aortic diseases was marginal (p =
      0.056). CONCLUSIONS: The carotid augmentation index is elevated in patients with
      aortic aneurysm and dissection.

PMID- 19379867
TI  - Invited commentary.

PMID- 19379868
TI  - Cardiac reoperation in patients aged 80 years and older.
AB  - BACKGROUND: The benefit of cardiac surgery in octogenarians is well described.
      Today, nearly every second patient who undergoes cardiac surgery is older than 70
      years. The time between primary cardiac surgery and reoperation is 7 to 13 years.
      Therefore, in the future we can expect to see an increasing number of
      reoperations in octogenarians. METHODS: We studied 71 patients (41 male) with a
      mean age of 83 +/- 2.8 years, who underwent cardiac reoperation between 1994 and
      2006. These patients were compared with 71 octogenarians who underwent primary
      cardiac operation. Patients were matched for age, sex, year of operation, and
      surgical procedure. Demographic profiles, operative data, long-term survival, and
      quality of life by the Short-Form 36-Item Health Survey questionnaire were
      analyzed. RESULTS: Average time between previous operation and reoperation was
      10.8 +/- 5.6 years (range: 1.7 to 30.6). The 30-day mortality rate was 14.7% in
      the reoperation group and 8.5% (p = 0.43) in the control group. Actuarial
      survival at 1, 3, and 6 years was 71% +/- 5.5%, 60.5% +/- 6.1%, and 30% +/- 8.1%
      for patients who underwent cardiac reoperation; and 77.2% +/- 5%, 58.3% +/- 6.3%,
      and 36.3% +/- 7.8% for matched octogenarians who underwent primary cardiac
      surgery (p = 0.68). No significant differences were found between groups
      regarding the physical health summarized score (40.7 +/- 9.4 versus 39.1 +/- 10;
      p = 0.55) and the mental health summarized score (51.9 +/- 10.9 versus 48 +/-
      12.9; p = 0.24) of the Short-Form 36-Item Health Survey questionnaire.
      CONCLUSIONS: Octogenarians exhibit a similar long-term survival and quality of
      life after primary and redo cardiac surgery. Therefore, cardiac reoperation
      should not be a contraindication per se in octogenarians.

PMID- 19379869
TI  - Invited commentary.

PMID- 19379870
TI  - Contemporary results show repeat coronary artery bypass grafting remains a risk
      factor for operative mortality.
AB  - BACKGROUND: Reoperative coronary artery bypass grafting (redo CABG) shows
      improving outcomes, but with varying degrees of improvement. We assessed
      contemporary outcomes after redo CABG to determine if redo status is still a risk
      factor for early postoperative complications and midterm survival. METHODS:
      Isolated CABG procedures (June 1, 2001 to May 31, 2008) within the Australasian
      Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database were included.
      Redo status as a predictor for early outcomes was assessed with logistic
      regression analysis. Midterm survival was determined from the National Death
      Index. Effect of redo status on midterm survival was assessed using a Cox
      proportional hazards model. RESULTS: Inclusion criteria were met by 13,436
      patients, and 458 (3.4%) underwent redo CABG. Operative mortality was 4.8% for
      redo CABG and 1.8% for first-time CABG (p < 0.001). After adjustment, redo status
      remained a predictor for operative mortality (odds ratio [OR], 2.1; 95%
      confidence interval [CI], 1.3 to 3.6), myocardial infarction (OR, 2.8; 95% CI,
      1.6 to 6.0), and prolonged ventilation (OR, 1.5; 95% CI, 1.1 to 2.0). Unadjusted
      survival was lower for the redo CABG group vs the first-time CABG group at up to
      6 years (p = 0.01, log-rank test. After adjusting for differences in patient
      variables, redo status was not a predictor of midterm survival (OR, 1.03; 95% CI,
      0.78 to 1.35; p = 0.85). CONCLUSIONS: Early postoperative outcomes of redo CABG
      are encouraging. Midterm survival is excellent; however, redo remains a
      significant risk factor for operative mortality in contemporary practice.

PMID- 19379871
TI  - Invited commentary.

PMID- 19379872
TI  - Decision-making for patients with patent left internal thoracic artery grafts to
      left anterior descending.
AB  - BACKGROUND: It is unknown whether coronary reintervention confers a survival
      advantage when a previously placed left internal thoracic artery graft to the
      left anterior descending coronary artery (LAD) is patent. We compared survival
      after medical therapy, percutaneous intervention, and reoperative coronary artery
      bypass grafting in such patients who developed non-LAD territory jeopardy.
      METHODS: From 1971 to 2000, 4,640 patients with prior coronary artery bypass
      grafting that included left internal thoracic artery to LAD grafting were found
      on angiography during active follow-up to have a patent left internal thoracic
      artery to LAD graft, but at least 50% stenosis of non-LAD territories or grafts
      to them. Two survival analyses were performed: (1) intent-to-treat, which
      included patients undergoing reoperative coronary artery bypass grafting (n =
      731) or percutaneous intervention (n = 994) within 6 weeks of angiography or
      medical management (n = 2,782), and (2) competing risk/crossover, in which
      patients were classified as medically managed until crossover to coronary artery
      bypass grafting or percutaneous intervention. RESULTS: In the intent-to-treat
      analysis, propensity-adjusted early (<1 year) survival was similar for all
      patients, but late survival was slightly better after percutaneous intervention
      than with medical management (p < or = 0.05). In the competing risk/crossover
      analysis, adjusted survival was best for medically treated patients early;
      however, late survival was similar among all three groups. CONCLUSIONS: Patients
      with patent left internal thoracic artery to LAD grafts who develop non-LAD
      territory jeopardy derive no survival benefit from reintervention, consistent
      with previous observations that for coronary reintervention to improve survival,
      the LAD territory must be jeopardized. Reintervention in patients with a patent
      left internal thoracic artery to LAD graft may be warranted to relieve symptoms,
      without expecting a survival benefit.

PMID- 19379874
TI  - Invited commentary.

PMID- 19379873
TI  - Long-term outcome of coronary artery bypass grafting in patients with left
      ventricular dysfunction.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is a well-accepted therapeutic
      strategy for patients with multivessel coronary artery disease and left
      ventricular dysfunction. The aim of the study was to evaluate long-term results
      after CABG in patients with preoperative left ventricular ejection fraction
      (LVEF) of 0.35 or less. METHODS: Data from 302 consecutive patients (mean age, 62
      +/- 8.7 years) with LVEF of 0.35 or less who had undergone CABG were analyzed.
      Epinephrine and enoximone with or without norepinephrine were used to increase
      cardiac index. Intra-aortic balloon pump or left ventricular assist devices, or
      both, were used in case of postoperative low output syndrome. RESULTS: Complete
      revascularization was achieved in 298 of 302 patients (98.7%); internal thoracic
      artery was used in 294 (97.4%). Operative mortality was 5.3%; independent
      predictors of operative mortality were emergency CABG (p = 0.005), history of
      ventricular arrhythmias (p = 0.007), and previous anterior myocardial infarction
      (p = 0.05). At follow-up, all-cause mortality was 30.8%, and 10-year survival was
      63% +/- 4%; independent predictors of late all-cause mortality were history of
      ventricular arrhythmias (p < 0.0001), chronic renal dysfunction (p = 0.0004), and
      diabetes mellitus (p = 0.04). Cardiac death was 20.4%, and 10-year freedom from
      cardiac death was 73% +/- 3.3%; independent predictors of cardiac death were
      history of ventricular arrhythmias (p = 0.004), chronic renal dysfunction (p =
      0.03), and more than one previous anterior myocardial infarction (p = 0.004). At
      80 +/- 44 months of follow-up, echocardiography showed significant LVEF
      improvement (0.43 +/- 0.09 versus 0.28 +/- 0.06, p < 0.0001). Ten-year freedom
      from myocardial infarction was 87% +/- 3%. CONCLUSIONS: Excellent long-term
      results after CABG can be expected for patients with LVEF of 0.35 or less.
      Complete revascularization and internal thoracic artery grafting are associated
      with high freedom from myocardial infarction. Careful treatment of arrhythmias,
      diabetes, and renal dysfunction is necessary to improve long-term survival.

PMID- 19379875
TI  - Transit-time blood flow measurements in sequential saphenous coronary artery
      bypass grafts.
AB  - BACKGROUND: Little information is available on transit-time flow measurements of
      sequential saphenous vein grafts. The aim of the study was evaluation of mean
      blood flow and pulsatility index of sequential saphenous vein grafts in a large
      population of patients operated on with coronary artery bypass grafting. METHODS:
      In 581 patients 1,390 grafts were nested into left internal mammary artery to
      left anterior descending artery, single vein grafts, or double and triple
      sequential vein grafts, and analyzed. RESULTS: Within the single vein graft group
      there were no differences between flow of grafts to different target vessels
      except for diagonals (diagonal versus obtuse marginal, p < 0.001; versus
      posterior descending artery, p = 0.035; versus right coronary artery, p = 0.003).
      Flows measured in single vein grafts were significantly lower than in double (p <
      0.001) and triple sequential vein grafts (p < 0.001). Flows were lower in double
      versus triple sequential vein grafts (p = 0.017) and higher in men versus women
      (p < 0.001). Mean pulsatility index of vein grafts were lower in the left versus
      the right coronary system, 2.0 +/- 0.01 and 2.4 +/- 0.06, respectively (p <
      0.001). Between sex and groups of vein grafts within each coronary system, mean
      pulsatility index had similar values. CONCLUSIONS: Blood flow increases from
      single to double and up to triple sequential grafts. Single grafts directed to
      diagonals have the lowest flow. Graft blood flows are higher in male versus
      female patients. Single, double, and triple saphenous vein grafts have similar
      pulsatility indexes. Pulsatility index of grafts to the right coronary system is
      significantly higher than that of grafts to the left coronary system.

PMID- 19379876
TI  - Invited commentary.

PMID- 19379877
TI  - Intermediate-term patency of saphenous vein graft with a clampless hand-sewn
      proximal anastomosis device after off-pump coronary bypass grafting.
AB  - BACKGROUND: To avoid complications related to aortic manipulation, devices were
      developed to perform clampless anastomosis. However, there are few studies
      concerning the late patency of the graft. The aims of this study were to
      investigate the patency rate of saphenous vein (SV) graft after off-pump coronary
      artery bypass grafting (OPCAB) and to evaluate the influence of a clampless hand
      sewn proximal anastomosis on late graft patency. METHODS: Patients (n = 232) were
      enrolled who underwent OPCAB with SV grafts from 2004 to 2007 and had follow-up
      angiography. For proximal anastomoses, a clampless device was used in 73 (group
      A; HEARTSTRING [Guidant Corporation, Santa Clara, CA] in 54, Enclose II [Novare
      Surgical Systems, Inc, Cupertino, CA] in 19), and partial clamping was used in
      159 (group B). The proximal anastomosis procedure was modified according to the
      results of epiaortic ultrasonography. Coronary angiography was performed early
      (11.8 +/- 10.4 days) and one-year postoperatively (n = 180, 371.5 +/- 102.6
      days). RESULTS: There were no significant differences in patient characteristics
      between the two groups except for a higher reoperation rate in group A. The
      overall SV patency rate at the early and one-year postoperative angiography was
      95.7% and 83.0%, respectively. The patency rates were similar between the two
      groups (early: 97.3% vs 98.1%, p = 0.729; 1 year: 87.0% vs 81.3%, p = 0.316).
      There was also no significant difference in the target vessel revascularization
      rate during follow-up (6.8% vs 10.1%, p = 0.623). CONCLUSIONS: Intermediate-term
      angiographic follow-up demonstrate an acceptable SV patency rate after OPCAB. The
      SV patency rate with a clampless device for proximal anastomosis is comparable
      with that with partial clamping during the first postoperative year.

PMID- 19379878
TI  - Long-term results after surgical repair of postinfarction ventricular septal
      rupture by infarct exclusion technique.
AB  - BACKGROUND: Ventricular septal defect (VSD) is one of the most serious and life
      threatening complications of acute myocardial infarction. The aim of this study
      was to evaluate the early and long-term results of the patients after surgical
      repair of postinfarction VSD by infarct exclusion technique. METHODS: A total of
      32 consecutive patients (mean age, 62.5 +/- 10.5 years) underwent postinfarction
      VSD repair using a standardized technique in our department. A retrospective
      analysis of clinical and operative data, predictors of early mortality, and long
      term survival was performed. The localization of VSD was posterior in 50% and
      anterior in 50% of the patients. RESULTS: The hospital mortality was 31.2% (10
      patients). The most common cause of hospital death was persistent low cardiac
      output. The mortality of the posterior VSD group was significantly lower than
      that of the anterior VSD group (18.7% and 43.7%, respectively, p = 0.01). Intra
      aortic balloon pump support and absence of cardiac shock were significantly
      associated with a lower risk of hospital mortality (p = 0.0001 and p = 0.0009,
      respectively). The actuarial survival rates of in-hospital survivors at 5 and 10
      years were 79% +/- 2% and 51% +/- 3%, respectively. CONCLUSIONS: The repair of
      postinfarction VSD by the infarct exclusion is feasible and safe. This technique
      seems to offer sufficient favorable early and long-term results compared with
      other techniques. Early indication, preoperative intra-aortic balloon pump
      support may improve the surgical results. Preoperative cardiogenic shock carries
      a poor prognosis for this patient group.

PMID- 19379879
TI  - Invited commentary.

PMID- 19379880
TI  - Reoperative mitral valve surgery by the port access minithoracotomy approach is
      safe and effective.
AB  - BACKGROUND: Reoperative mitral valve (MV) surgery through sternotomy can be
      technically challenging. Limited exposure and injury to the right ventricle or
      patent grafts (previous coronary artery bypass graft surgery [CABG]) are
      potential complications upon sternal reentry. The purpose of this study was to
      examine the results of port access MV surgery through right minithoracotomy in
      patients with previous cardiac surgery performed through median sternotomy.
      METHODS: From 1998 through July 2007, 651 port access MV procedures were
      performed. In 107 patients (16.4%), previous cardiac surgery had been performed
      through midline sternotomy. Mean age was 67.5 +/- 11.2 years, and 60.7% (n = 65)
      were male. Previous surgery included CABG (n = 45, 42.1%), aortic valve
      replacement (n = 9, 8.4%), aortic valve replacement/MV repair (n = 2, 1.9%), MV
      repair (n = 21, 19.6%), MV replacement (n = 5, 4.7%), CABG/MV replacement (n = 1,
      0.9%), CABG/MV repair (n = 8, 7.5%), CABG/aortic valve replacement (n = 2, 1.9%),
      and others (n = 14, 13.1%). New York Heart Association functional classes were I
      (n = 2, 1.9%), II (n = 28, 26.2%), III (n = 50, 46.7%), and IV (n = 27, 25.2%).
      The endoaortic balloon was used in 75 patients (70.1%) and the Chitwood clamp in
      11 patients (10.2%). In the remaining patients (n = 21, 19.6%), fibrillatory
      arrest was employed. RESULTS: Mitral valve repair and MV replacement were
      performed in 60 patients (56.1%) and 47 patients (43.9%), respectively. The 30
      day mortality was 4.7% (n = 5). The mean cardiopulmonary bypass and aortic cross
      clamp times were 140.8 +/- 43.7 minutes and 77.0 +/- 49.7 minutes, respectively.
      Complications included 6 reoperations for bleeding (5.6%), 1 stroke (0.9%), and 2
      wound infections (1.9%). Conversion to sternotomy was required in 1 patient
      (0.9%) because of an acute type A dissection secondary to aortic occlusion with
      Chitwood clamp. The mean hospital stay was 9.6 days. During follow-up,
      reoperation for failure of MV repair was performed in 4 patients (3.7%).
      CONCLUSIONS: Reoperative port access MV surgery can be performed with minimal
      morbidity and mortality. This approach may be the preferred technique for
      patients who require MV procedures after previous cardiac surgery performed
      through median sternotomy.

PMID- 19379881
TI  - Trends in mitral valve surgery in the United States: results from the Society of
      Thoracic Surgeons Adult Cardiac Surgery Database.
AB  - BACKGROUND: The purpose of this study is to examine trends in mitral valve (MV)
      repair and replacement surgery using The Society of Thoracic Surgeons Adult
      Cardiac Surgery Database (STS ACSD). METHODS: The study population included
      isolated mitral valve operations performed between January 2000 and December 2007
      at 910 hospitals participating in the STS ACSD. Patients with endocarditis, prior
      cardiac operation, shock, emergency operation, and concomitant coronary artery
      bypass graft or aortic valve surgery were excluded. RESULTS: During the 8-year
      study period, 58,370 patients underwent isolated primary MV operations. For
      patients with isolated mitral regurgitation (n = 47,126), the rate of MV repair
      (versus replacement) increased from 51% to 69% (p < 0.0001). Among patients
      having replacement (n = 24,404), there has been a pronounced decline in the use
      of mechanical valves: 68% to 37% (p < 0.0001). The operative mortality for MV
      replacement was consistently higher than that for repair (3.8% versus 1.4%), a
      finding that persisted after risk-adjustment (adjusted odds ratio 0.52, 95%
      confidence interval: 0.45 to 0.59; p < 0.0001). Among patients having elective
      isolated MV repair (n = 28,140), the operative mortality was 1.2%. For
      asymptomatic (class I) patients, operative mortality was 0.6%. CONCLUSIONS: This
      study documents several important trends in MV surgery, including the progressive
      adoption of mitral valve repair and increasing use of bioprosthetic replacement
      valves. Operative risks of MV repair are significantly lower than those for MV
      replacement. Operative mortality for isolated elective mitral valve repair is 1%
      in contemporary clinical practice.

PMID- 19379882
TI  - Aortic valve replacement in octogenarians: utility of risk stratification with
      EuroSCORE.
AB  - BACKGROUND: With the advent of percutaneous valve implantation, an increasing
      amount of interest is being expressed in outcomes of conventional aortic valve
      replacement (AVR) in elderly patients. We evaluated characteristics and outcomes
      of elderly patients undergoing isolated AVR with a particular focus on the
      European System for Cardiac Operative Risk Evaluation (EuroSCORE) risk
      stratification. METHODS: All patients aged 80 years or older (n = 282) undergoing
      isolated AVR between November 1995 and June 2006 at our institution were reviewed
      according to logistic EuroSCORE (ES(log)) risk stratification. Surgical risk was
      defined as low risk (ES(log) < or = 10% [n = 107]), moderate risk (10% < ES(log)
      < 20% [n = 103]), and high risk (ES(log) > or = 20% [n = 72]). Patient age was 82
      +/- 2 years (low risk), 82.7 +/- 2.7 years (moderate risk), and 83.6 +/- 3.1
      years (high risk), respectively (p < 0.05). Mean ES(log) predicted risk of
      mortality was 7.3% +/- 1.4% (low risk), 13.7% +/- 2.5% (moderate risk), and 33.0%
      +/- 11.5% (high risk; p < 0.05). Follow-up was 99.7% complete. RESULTS: In
      hospital mortality was 7.5% (low risk), 12.6% (moderate risk), and 12.5% (high
      risk; p = 0.4). One-year survival was 90%, 78%, and 69% (p = 0.002); 5-year
      survival was 70%, 53%, and 38% (p = 0.05); and 8-year survival was 38%, 33%, and
      21% (p = 0.017), for low-, moderate-, and high-risk patients, respectively.
      Independent predictors for in-hospital mortality were pulmonary hypertension and
      urgent indication for surgery. Cox regression predictors of medium-term survival
      were congestive heart failure, urgent timing, previous stroke or transient
      ischemic attack, and EuroSCORE stratum. CONCLUSIONS: Aortic valve replacement can
      be performed in the elderly population with acceptable outcomes. EuroSCORE risk
      stratification is imprecise for prediction of perioperative mortality among
      octogenarian AVR patients, but may be useful for predicting mortality during
      medium-term follow-up.

PMID- 19379883
TI  - Laser-assisted extraction of pacemaker and defibrillator leads: the role of the
      cardiac surgeon.
AB  - BACKGROUND: The development of laser-assisted extraction techniques for
      chronically implanted pacemaker and defibrillator leads has reduced the need for
      open surgical removal. Reports of the mortality from laser-assisted extraction
      range from 1.9% to 3.4%. The purpose of this study was to determine the rate of
      major cardiovascular injury and emphasize the need for cardiothoracic surgical
      participation in this procedure. METHODS: A retrospective cohort study was
      performed of 112 consecutive laser-assisted lead extractions at a single
      university medical center during a 6-year period. Patient and lead
      characteristics were analyzed as well as indications, outcomes, and major
      complications. RESULTS: Successful lead extraction was accomplished in 103 (92%)
      of the 112 patients. Elective sternotomy after failure of laser-assisted lead
      removal was successfully performed in 4 patients. Emergent surgical intervention
      was required in 4 patients for caval perforation (n = 2), subclavian vein injury
      (n = 1), or right atrial injury (n = 1). Three of the 4 patients requiring
      emergent intervention died, for an overall series mortality of 2.6%. In July of
      2006, a policy of cardiothoracic surgeon presence during the laser-assisted
      extraction was instituted. Since that time, there has been one emergent
      sternotomy and one elective sternotomy for lead removal with no procedure-related
      deaths. CONCLUSIONS: Despite recent advances in laser technology for the removal
      of pacemaker and defibrillator leads, the potential for major cardiovascular
      injury and death remains. Involvement of the cardiothoracic surgeon in both the
      preoperative decision-making process as well as the laser-assisted lead
      extraction is critical to prevent or emergently treat any major complications.

PMID- 19379884
TI  - Intermediate-term outcomes of surgical atrial fibrillation correction with the
      CryoMaze procedure.
AB  - BACKGROUND: Few studies have reported long-term outcomes of surgical atrial
      fibrillation (AF) correction. We perform the Cox-Maze III lesion set with argon
      powered cryoenergy (CryoMaze procedure) on all patients with AF presenting for
      cardiac operations. This study reports long-term clinical results and heart
      rhythm status. METHODS: Between July 2002 and November 2005, 119 consecutive
      patients underwent surgical AF correction with the CryoMaze procedure. Mitral
      valve disease was the primary indication for operation in 66%. AF was continuous
      in 65%. Rhythm assessment was with 2-week continuous electrocardiographic (ECG)
      monitoring in 75% of patients and by noncontinuous ECG in the remainder. Median
      follow-up was 3.2 years and was 98% complete. RESULTS: There was one hospital
      (0.8%) death. Survival at 3 years was 84%. One perioperative stroke resolved
      completely. No late strokes occurred. In 4 of 119 patients (4 (3.4%), pacemakers
      were inserted during the index hospitalization. Median length of stay was 7 days.
      Overall freedom from AF more than 3 years after operation was 60%. Among patients
      with preoperative intermittent AF, 85% (28 of 33) were in normal sinus rhythm,
      and 47% (27 of 58) with continuous AF were in normal sinus rhythm (p < 0.001).
      CONCLUSIONS: CryoMaze AF correction is safe and is associated with a very low
      risk of stroke. Rates of normal sinus rhythm at more than 3 years postoperatively
      were high for patients with intermittent AF and acceptable for those with
      continuous AF. This experience supports wider application of the CryoMaze to all
      patients with AF who need cardiac operations.

PMID- 19379885
TI  - Model for end-stage liver disease predicts mortality for tricuspid valve surgery.
AB  - BACKGROUND: Patients undergoing tricuspid valve surgery have a mortality of 9.8%,
      which is higher than expected given the complexity of the procedure. Despite
      liver dysfunction seen in many patients with tricuspid disease, no existing risk
      model accounts for this. The Model for End-Stage Liver Disease (MELD) score
      accurately predicts mortality for abdominal surgery. The objective of this study
      was to determine if MELD could accurately predict mortality after tricuspid valve
      surgery and compare it to existing risk models. METHODS: From 1994 to 2008, 168
      patients (mean age, 61 +/- 14 years; male = 72, female = 96) underwent tricuspid
      repair (n = 156) or replacement (n = 12). Concomitant operations were performed
      in 87% (146 of 168). Patients with history of cirrhosis or MELD score 15 or
      greater (MELD = 3.8*LN [total bilirubin] + 11.2*log normal [international
      normalized ratio] + 9.6*log normal [creatinine] + 6.4) were compared with
      patients without liver disease or MELD score less than 15. Preoperative risk,
      intraoperative findings, and complications including operative mortality were
      evaluated. Statistical analyses were performed using chi(2), Fisher's exact test,
      and area under the curve (AUC) analyses. RESULTS: Patients with a history of
      liver disease or MELD score of 15 or greater had significantly higher mortality
      (18.9% [7 of 37] versus 6.1% [8 of 131], p = 0.024). To further characterize the
      effect of MELD, patients were stratified by MELD alone. No major differences in
      demographics or operation were identified between groups. Mortality increased as
      MELD score increased, especially when MELD score of 15 or greater (p = 0.0015). A
      MELD score less than 10, 10 to 14.9, 15 to 19.9, and more than 20 was associated
      with operative mortality of 1.9%, 6.8%, 27.3%, and 30.8%, respectively. By
      multivariate analysis, MELD score of 15 or greater remained strongly associated
      with mortality (p = 0.0021). The MELD score predicted mortality (AUC = 0.78) as
      well as the European System for Cardiac Operative Risk Evaluation logistic risk
      calculator (AUC = 0.78, p = 0.96). CONCLUSIONS: The MELD score predicts mortality
      in patients undergoing tricuspid valve surgery and offers a simple and effective
      method of risk stratification in these patients.

PMID- 19379886
TI  - The long-term cognitive and functional outcomes of postoperative delirium after
      cardiac surgery.
AB  - BACKGROUND: Delirium or acute confusion is a temporary mental disorder, which
      occurs frequently among hospitalized elderly patients. Patients who undergo
      cardiac surgery have an increased risk of developing delirium. This is associated
      with many negative consequences such as prolonged hospital stay, nursing home
      placement, and reduced cognitive and functional recovery. METHODS: In this
      prospective follow-up study, a questionnaire was used 1 to 1.5 years after
      cardiac surgery in our earlier cohort of 112 patients who underwent elective
      cardiac surgery, of which 24 patients (21%) developed postoperative delirium as
      diagnosed by a single psychiatrist. RESULTS: Postoperative delirium after cardiac
      surgery may be associated with increased mortality (12.5% in patients with
      delirium versus 4.5% in patients without delirium; p = 0.16), more readmissions
      to the hospital (47.6% vs 32.6%; p = 0.19), dysfunction in memory (31.6% vs
      22.6%; p = 0.39), and concentration problems (36.8% vs 20.2%; p = 0.13); and is
      associated with sleep disturbance (47.4% vs 23.8%; p = 0.03). CONCLUSIONS:
      Postoperative delirium after cardiac surgery may be associated with increased
      mortality and readmissions to the hospital, as well as poorer cognitive and
      functional outcomes. Therefore, prevention and (or) early recognition of delirium
      must be improved. In addition, patients and caregivers (family and general
      practitioner) must be better informed about the long-term consequences of
      delirium and what they can do about it.

PMID- 19379887
TI  - Invited commentary.

PMID- 19379888
TI  - Superior vena cava to pulmonary artery anastomosis as an adjunct to biventricular
      repair: 38-year follow-up.
AB  - BACKGROUND: The working hypothesis for a one and a half ventricle repair has been
      that the benefits of a pulsatile pulmonary circulation may negate some of the
      late complications of the Fontan procedure. Those benefits are thought to
      outweigh the downside risk of having retrograde pulsatility in the superior vena
      cava. We sought to define the long-term fate of this strategy. METHODS: One
      hundred fourteen patients who underwent a superior vena cava to pulmonary artery
      anastomosis as an adjunct to biventricular repair were identified for the years
      1965 to 2003. Median follow-up was 92.3 months (range, 1 month to 38 years).
      RESULTS: The long-term outcome for operative survivors was 83.4%, 80.1%, and
      69.3% at 5, 10, and 20 years, respectively. The survival in the most recent 10
      years is 91.8% (p = 0.063). Of the late deaths, 69.6% (16 of 23) were known
      cardiac deaths or sudden. Patients with chronic right ventricular dysfunction
      demonstrated the best 10-year survival (91.6%). Of the late survivors, 98.8% of
      patients are in New York Heart Association class I or II. Arterial O(2)
      saturation increased significantly from before to late after repair. (83.5% to
      94.5%, p < 0.001; n = 82). Freedom from new atrial arrhythmia was 92.2% at 20
      years. The superior vena cava to pulmonary artery anastomosis was taken down in
      3. There was no patient with clinically evident protein-losing enteropathy.
      CONCLUSIONS: The most common cause of late mortality is cardiac. Atrial and
      ventricular arrhythmias occur, but no protein-losing enteropathy was identified.
      The serious complication risk related to pulsatility in the superior vena cava
      was 2.6%.

PMID- 19379889
TI  - Perioperative risks and outcomes of atrioventricular valve surgery in conjunction
      with Fontan procedure.
AB  - BACKGROUND: Long-term outcomes of staged single-ventricle palliation can be
      impaired by atrioventricular valve (AVV) regurgitation. Atrioventricular valve
      repair or replacement has been shown to improve late outcomes, but little data
      exist regarding the associated perioperative morbidity. This study aimed to
      evaluate the additional perioperative risks associated with single-ventricle AVV
      surgery. METHODS: Two hundred thirty-six consecutive Fontan procedures were
      retrospectively reviewed. Group 1 (n = 21, with concomitant AVV repair [n = 19]
      or replacement [n = 2]) was compared with group 2 (n = 215, no AVV surgery) with
      regard to preoperative characteristics and perioperative outcomes.
      Atrioventricular valve regurgitation was graded as 1 (none or trivial) to 4
      (severe). RESULTS: Group 1 patients were older (4.3 +/- 3.7 versus 3.0 +/- 2.6
      years; p = 0.04) and had longer cardiopulmonary bypass (118 +/- 38 versus 85 +/-
      28 minutes; p < 0.001) and aortic cross-clamp times (33 +/- 32 versus 14 +/- 21
      minutes; p < 0.001). There were no differences between groups regarding
      diagnosis, weight, hospital or intensive care unit length of stay, ventilator
      time, or 12-hour chest tube output. Postoperative complications were similar
      between groups, including bleeding (0 of 21 versus 8 of 215; p = 0.8), neurologic
      injury (1 of 21 versus 9 of 215; p = 0.7), arrhythmias (1 of 21 versus 24 of 215;
      p = 0.6), and operative mortality (0 of 21 versus 1 of 215; p = 0.1). Group 1 AVV
      regurgitation significantly decreased after surgery (3.0 +/- 0.9 preoperatively
      versus 1.7 +/- 0.9 postoperatively; p < 0.001). CONCLUSIONS: Atrioventricular
      valve surgery has been shown to improve late outcomes for single-ventricle
      patients. This study demonstrates that AVV surgery performed with the Fontan
      procedure increased operative times, but did not significantly increase
      perioperative morbidity or mortality. This information supports appropriate
      utilization of AVV surgery for single-ventricle patients.

PMID- 19379890
TI  - Postoperative cerebral oxygenation in hypoplastic left heart syndrome after the
      Norwood procedure.
AB  - BACKGROUND: Cerebral near-infrared spectroscopy (NIRS) is being used with
      increasing frequency in the care of pediatric patients after surgery for
      congenital heart disease. Near-infrared spectroscopy provides a means of
      evaluating regional cerebral oxygen saturation (cSaO(2)) noninvasively, with
      correlations to cardiac output and central venous saturation. Prior studies have
      demonstrated that systemic venous saturation can predict outcome after the
      Norwood procedure. With this in mind, we sought to determine whether regional
      cSaO(2) by NIRS technology could predict risk of adverse outcome after the
      Norwood procedure. METHODS: We reviewed the first 48 hours of postoperative
      hemodynamic data on 50 patients with hypoplastic left heart syndrome at our
      institution who underwent the Norwood procedure. Cerebral oxygen saturation data
      within 48 hours of surgery were analyzed for association with subsequent adverse
      outcome, which was defined as intensive care unit length of stay greater than 30
      days, need for extracorporeal membrane oxygenation, or hospital death after 48
      hours. RESULTS: There were 18 adverse events among the 50 subjects. The mean
      cSaO(2) for the entire cohort at 1 hour, 4 hours, and 48 hours after surgery was
      51% +/- 7.5%, 50% +/- 9.4%, and 59% +/- 8.1%, respectively. Mean cSaO(2) for the
      first 48 postoperative hours of less than 56% was a risk factor for subsequent
      adverse outcome (odds ratio 11.9, 95% confidence interval: 2.5 to 55.8). Mean
      cerebral NIRs of less than 56% over the first 48 hours after surgery yielded a
      sensitivity of 75.0% and a specificity of 79.4% to predict those at risk for
      subsequent adverse events. CONCLUSIONS: Low regional cerebral oxygen saturation
      by NIRS in the first 48 hours after the Norwood procedure has a strong
      association with subsequent adverse outcome. Monitoring of cerebral saturation
      can serve as a valuable monitoring tool and can identify patients at risk for
      poor outcome.

PMID- 19379891
TI  - Invited commentary.

PMID- 19379892
TI  - Common arterial trunk with atrioventricular septal defect: new observations
      pertinent to repair.
AB  - BACKGROUND: The coexistence of abnormalities in both atrioventricular and
      ventriculoarterial junctions occasionally represents a formidable challenge to
      the surgeon. The association of common arterial trunk with atrioventricular
      septal defect is such an example. To date, only two reports have described
      successful operative outcome. This paucity of success might reflect the
      anatomical complexity that could prevent favorable results. METHODS: We reviewed
      six specimens with common arterial trunk and atrioventricular septal defect,
      focusing on how to establish a nonobstructed connection between the left
      ventricle and the truncal valve. RESULTS: In all cases, the common trunk arose
      exclusively from the right ventricle, and the only exit from the left ventricle
      was the ventricular component of the septal deficiency. In particular, the
      preferential route was limited to a space below the superior bridging leaflet
      that did not have any tendinous cords inserting onto the ventricular crest, in
      contrast to the inferior bridging leaflets that were always tethered to the crest
      with many short cords. Accordingly, the size of potential left ventricular
      outflow depended on the shape of the anterosuperior margin of the ventricular
      crest below the superior bridging leaflet. The potential outflow was narrower
      than the truncal valvar area in all hearts but one having extensive
      anterosuperior excavation of the ventricular crest, suggesting the necessity of
      septal enlargement had anatomical repair been attempted during life. CONCLUSIONS:
      Owing to the unique ventriculoarterial connection, the surgeon, considering
      anatomical repair, needs to pay attention to the anterosuperior margin of the
      ventricular scoop, which determines the adequacy of left ventricular outflow
      size.

PMID- 19379893
TI  - Invited commentary.

PMID- 19379894
TI  - Twenty-year surgical experience with congenital supravalvar aortic stenosis.
AB  - BACKGROUND: Congenital supravalvar aortic stenosis (SVAS) is an arteriopathy
      associated with Williams-Beuren syndrome and other elastin gene deletions. Our
      objectives were to review outcomes of congenital SVAS repair and to compare
      prosthetic patch repair techniques to all-autologous slide aortoplasty. METHODS:
      Congenital SVAS repairs from 1988 to 2008 were retrospectively reviewed. Peak
      instantaneous gradients were estimated by Doppler interrogation. Variables were
      compared by either Student's t test or Fisher's exact test. Risk factors were
      analyzed by chi(2) test. Survival was estimated by the Kaplan-Meier method.
      RESULTS: Of 25 primary SVAS repairs, there were 10 all-autologous slide
      aortoplasties and 15 prosthetic patch aortoplasties. The prosthetic patch group
      included the Doty technique (n = 9), patch-augmented slide aortoplasty (n = 3),
      modified Brom technique (n = 1), interposition graft (n = 1), and two-sinus patch
      with transverse arch augmentation (n = 1). There was 1 early and 1 late death.
      Cumulative survival for all patients was 96% at 5 and 10 years. Event-free
      survival did not differ between groups (p = 0.481). There were 2 late
      reoperations (both were prosthetic patch patients with bicuspid aortic valve: 1
      with recurrent aortic valve stenosis and 1 with aortic insufficiency). Bicuspid
      aortic valve was the only risk factor for reoperation (p = 0.003). Three patients
      weighing less than 10 kg with diffuse disease underwent attempted slide
      aortoplasty: 2 required patch augmentation and 1 had a recurrent gradient in less
      than 1 year postoperatively. CONCLUSIONS: Outcomes after SVAS repair were good by
      any technique. No advantage to all-autologous slide aortoplasty was apparent at
      current follow-up. Based on our experience, slide aortoplasty is not recommended
      for small patients with diffuse disease.

PMID- 19379895
TI  - Is there an optimal timing for surgical ligation of patent ductus arteriosus in
      preterm infants?
AB  - BACKGROUND: We sought to define the variables associated with hospital outcome in
      preterm infants with patent ductus arteriosus (PDA) and identify the optimal
      timing for PDA closure to improve hospital outcome. METHODS: Included were 201
      premature babies (< or = 32 weeks gestational age), from January 2001 to June
      2007, with PDA who received primary medical treatment with ibuprofen. Number of
      ibuprofen cycles, gestational age, body weight, and presence of symptomatic
      hypotension requiring vasoactive/inotropic drugs were related to hospital
      outcome, including hospital mortality, presence of necrotizing enterocolitis,
      acute renal failure, intraventricular hemorrhage, retinopathy and
      bronchopulmonary dysplasia at week 36. Data were analyzed with a logistic
      regression model. RESULTS: Medical treatment was effective in 149 patients (75%),
      but 52 (25%) required surgical ligation after medical treatment failed. They had
      younger gestational age (25 weeks [IQR, 24 to 27 weeks] vs 27 weeks [IQR, 25 to
      28 weeks], p < 0.0001), lower body weight at birth (730 g [IQR, 595 to 915 g] vs
      840 g [IQR, 670 to 1016], p = 0.05), and a higher incidence of symptomatic
      hypotension (38 of 52 [73%] vs 56 of 149 [38%], p < 0.0001) than patients who
      responded to ibuprofen. More than two cycles of ibuprofen was significantly
      associated with an increased risk for bronchopulmonary dysplasia (odds ratio
      [OR], 2.81; p = 0.03) and acute renal failure (OR, 3.81; p = 0.09). CONCLUSIONS:
      The prolonged patency of the ductus arteriosus in preterm infants is related to
      an increased morbidity. Surgical ligation of PDA is a safe and effective
      treatment and should be done soon after two complete cycles of ibuprofen,
      especially in selected patients, to improve clinical outcome.

PMID- 19379896
TI  - Pediatric cardioplegia strategy results in enhanced calcium metabolism and lower
      serum troponin T.
AB  - BACKGROUND: Pediatric myocardium is unique from mature myocardium; thus, the use
      of adult cardioplegia for pediatric cardiac operations may provide suboptimal
      myocardial protection. We evaluated our standard adult cardioplegia (AC; modified
      Buckberg) and a pediatric cardioplegia (PC) solution (del Nido solution, Baxter)
      in vitro in rat cardiomyocytes and compared short-term outcomes in pediatric
      cardiac surgical patients. METHODS: Contractions, intracellular calcium, and
      action potentials were recorded from isolated rat cardiomyocytes exposed to PC or
      AC, followed by reperfusion. Pediatric patients (n = 118) undergoing cardiac
      operations using PC (group PC, n = 59) or AC (group AC, n = 59) were matched 1:1
      for age, diagnosis, and duration of cardiopulmonary bypass. RESULTS: PC-perfused
      rat ventricular cardiomyocytes had lower diastolic calcium during cardioplegia
      and early reperfusion than AC-perfused cardiomyocytes. Cardiomyocytes remained
      excitable despite introduction of AC but not PC. The mean age in each pediatric
      group was 3.7 years (range, 3 days to 17 years; p = 0.95). Median serum troponin
      T levels at intensive care admission were significantly lower in group PC (0.83
      +/- 0.25 microg/L) than in group AC (13.8 +/- 12.7 microg/L, p = 0.0001), which
      persisted at 24 hours postoperatively. There were no significant differences in
      duration of intubation or length of stay in intensive care or the hospital.
      CONCLUSIONS: Pediatric cardioplegia is associated with reduced intracellular
      diastolic calcium during arrest and reperfusion and more complete arrest during
      exposure in rat cardiomyocytes. Pediatric patients receiving pediatric
      cardioplegia had reduced troponin T release compared with those receiving adult
      cardioplegia.

PMID- 19379897
TI  - Invited commentary.

PMID- 19379898
TI  - Choice of first intervention is related to outcomes in the management of empyema.
AB  - BACKGROUND: The study determined whether the first procedure; simple drainage
      (tube thoracostomy, pigtail catheter) or operation (video-assisted thoracic
      surgery [VATS], thoracotomy) was related to outcomes in the management of
      empyema. METHODS: Data were collected from 104 consecutive patients with empyema.
      Primary outcomes were additional procedures and death. Predictor variables
      included age, delay, Karnofsky performance status (KPS), Charlson comorbidity
      index (CCI), serum albumin, malignancy, Acute Physiology and Chronic Health
      Evaluation II score, loculations on computed tomography scan, empyema stage, and
      first procedure choice. RESULTS: Advanced empyema (> or = stage IIA) was present
      in 84% of patients. Overall treatment success rates (no death, no additional
      drainage procedures) among evaluable patients for pigtail drainage, tube
      thoracostomy, VATS, and thoracotomy were 40% (4 of 10), 38% (14 of 37), 81% (13
      of 16), and 89% (32 of 36), respectively. Five patients underwent miscellaneous
      procedures. Univariate variables associated with hospital death included KPS,
      CCI, and drainage as the first procedure. In multivariate analyses, KPS
      (coefficient, -0.06, p = 0.002) and failure of the first procedure (odds ratio
      [OR], 6.76; 95% confidence interval [CI], 1.45 to 31.4, p = .01) were independent
      predictors of death. Simple drainage as the first procedure was a strong,
      independent predictor of failure of the first procedure (OR, 11.1; 95% CI, 3.51
      to 34.9; p = .00004). CONCLUSIONS: The choice of the first procedure is critical
      in the outcome for treatment of empyema, even with adjustment for confounding
      variables. VATS or thoracotomy as initial therapy for advanced empyema is
      associated with better outcomes.

PMID- 19379899
TI  - Surgical management of invasive pulmonary fungal infection in hematology
      patients.
AB  - BACKGROUND: The purpose of this study was to analyze our institutional results
      with pulmonary resection in neutropenic patients with hematologic malignancies
      and suspected invasive pulmonary fungal infections. METHODS: We performed a
      retrospective medical record review of 25 immunocompromised patients with
      hematologic malignancies who underwent pulmonary resection between 2000 and 2007.
      We analyzed preoperative diagnostic technique, degree of pulmonary resection, and
      postoperative morbidity and mortality to determine whether surgery is a viable
      treatment option in this subset of patients. RESULTS: Twenty-three of 25 patients
      had a minithoracotomy compared with 2 who had video-assisted thorascopic surgery
      resection only. Thirteen had wedge resections, 9 had lobectomies, and 3 had
      segmentectomies. Early surgical morbidity was 2 of 25, involving 1 pneumothorax
      and 1 empyema. In-hospital mortality was 2, with 1 death primarily related to
      surgery. Median survival was 342 days, and survival was significantly better in
      patients with only one lesion. No patient experienced late recurrence of invasive
      pulmonary fungal infection. Resected pulmonary tissue also provided the best
      chance for a proven diagnosis in 19 of 25 (76%). CONCLUSIONS: This study confirms
      that pulmonary resection in high-risk immunocompromised patients with suspected
      invasive fungal infection can be carried out with excellent operative morbidity
      and mortality.

PMID- 19379900
TI  - Fluid drainage and air evacuation characteristics of Blake and conventional
      drains used after pulmonary resection.
AB  - BACKGROUND: The Blake drain (BD) has recently begun to be used as a chest tube
      after pulmonary resection; however, its fluid drainage and air evacuation
      characteristics remain unclear. We compared the performance of the 19F BD with
      that of the 32F conventional drain (CD). METHODS: We studied 148 consecutive
      patients (74 with BD; 74 with CD) who underwent pulmonary resection.
      Postoperative drainage rates (daily drainage and total drainage) were analyzed to
      assess fluid drainage. Air evacuation was evaluated to determine whether
      subcutaneous emphysema or insufficient residual lung expansion developed when air
      leakage occurred. The BD group was initially managed with water seal or suction,
      whereas the CD group was managed with water seal. Furthermore, we experimentally
      measured the evacuation pressure required to expel a constant volume of air
      through various chest tubes to determine basic air evaluation performance of the
      tubes. RESULTS: Drainage rates on the operative day were significantly lower in
      the BD group than in the CD group, but were similar in both groups on the
      following day with greater variation in the water-sealed BD group. Among cases
      with air leakage, air evacuation insufficiency was more frequent in the BD group
      (16 of 22, 73%) than in the CD group (4 of 17, 24%; p = 0.004). The experiment
      revealed that air evacuation performance of the 19F BD was equivalent to that of
      the 12F CD, indicating that the BD requires higher intrathoracic pressure for air
      evacuation. CONCLUSIONS: Suction is required for the BD to obtain fluid drainage
      performance comparable to that of the water-sealed CD. When air leakage occurs,
      air evacuation by the BD tends to be insufficient, irrespective of suction
      conditions.

PMID- 19379901
TI  - Invited commentary.

PMID- 19379902
TI  - Open lobectomy simulator is an effective tool for teaching thoracic surgical
      skills.
AB  - BACKGROUND: Simulation has long been appreciated and used in professional
      industry training. The effectiveness of high-fidelity, low-cost simulators in
      such settings has led to its integration into surgical education for skill
      development. Simulation may possibly have a role in surgical specialty training.
      METHODS: Replicas of a human torso with a posterolateral thoracotomy incision
      were constructed from poultry netting and casting fiberglass, and used to house a
      previously prepared bovine lung. After reviewing computerized instructional
      material, student volunteers were asked to perform a lobectomy with the
      assistance of a thoracic surgeon, who also evaluated the subjects. Objective data
      were collected from knowledge-based examinations and technical skills evaluation
      scales. Statistical analysis was performed with the Student's t test. RESULTS:
      The initial success rate was 88.9% (16 of 18). Significant improvements were
      appreciated in both subjective and objective measures by the third week with
      weekly repetition. The average operative time was reduced to 34.8 +/- 5 minutes
      from 48.5 +/- 4.9 minutes (p = 0.01). The average task-specific score was 7.8 +/-
      0.8 (versus 5.6 +/- 2.1; p = 0.05), and students achieved an average global
      performance score of 28.6 +/- 3.8 (p = 0.01). Scores on knowledge-based
      examinations also significantly improved. CONCLUSIONS: This open lobectomy
      simulation can be used to effectively teach thoracic surgery techniques. Our
      results prove the effectiveness of simulation training in thoracic surgery.
      Additional studies will determine whether simulation is effective for different
      training levels in thoracic surgery.

PMID- 19379903
TI  - Prognostic features of long-term survivors after surgical management of malignant
      pleural mesothelioma.
AB  - BACKGROUND: The primary aim of this study was to evaluate prognostic features of
      long-term survivors with pleural mesothelioma. METHODS: Overall survival outcome
      was analyzed in 456 patients with malignant pleural mesothelioma who underwent
      extrapleural pneumonectomy (EPP), pleurectomy/decortications, or
      pleurodesis/biopsy with at least 18 months of follow-up. Prospectively collected
      clinicopathologic and treatment data were assessed for their correlations with
      actual 18-month survivors in both univariate and multivariate analyses. RESULTS:
      The actual 18-month survival was 28%. Epithelial subtype was present in 185
      patients (41%) and nonepithelial subtype in 183 (40%). Procedures were EPP in 59
      patients (13%), pleurectomy/decortication in 250 (55%), and pleurodesis/biopsy in
      147 (32%). Forty-two patients (9%) underwent positron emission tomography (PET)
      scanning. Forty patients (9%) received adjuvant radiotherapy and 45 (10%)
      received postoperative pemetrexed combination chemotherapy. In univariate
      analysis, age 65 years or younger (p < 0.001), malignant pleural effusion (p =
      0.041), epithelial subtype (p < 0.001), EPP (p < 0.001), PET scan (p = 0.012),
      adjuvant radiotherapy (p = 0.042), and postoperative pemetrexed combination
      chemotherapy (p = 0.035) were strongly associated with 18-month survivors. In
      multivariate analysis, epithelial histopathologic subtype (p < 0.001) and EPP (p
      < 0.001) were independently associated with 18-month survivors. CONCLUSIONS: The
      actual 18-month survival was 28% in 456 pleural mesothelioma patients who
      underwent operation. Epithelial histologic subtype and EPP were identified as
      independent predictors for 18-month survivors.

PMID- 19379904
TI  - Invited commentary.

PMID- 19379905
TI  - The risk of esophageal resection after esophagomyotomy for achalasia.
AB  - BACKGROUND: Esophagomyotomy is the mainstay of treatment for achalasia with
      proven long-term success. However, in patients with a significantly dilated
      esophagus, many advocate esophageal resection thus forgoing an esophagomyotomy.
      The purpose of this study is to determine the esophagomyotomy failure rate in
      patients with achalasia. METHODS: A retrospective review of all patients with
      achalasia who underwent an esophagomyotomy from 1996 to 2006; 272 patients were
      divided into three groups based on their preoperative degree of esophageal
      dilation for comparison. The endpoint for esophagomyotomy failure was persistent
      symptoms requiring any intervention. RESULTS: The preoperative characteristics
      were comparable except for the severely dilated esophagus patients who had a
      longer duration of preoperative symptoms. Group I (mild dilatation) had 162
      patients with 7 failures requiring intervention. Group II (moderate dilatation)
      had 74 patients with 4 failures and group III (severe dilatation) had 36 patients
      with 5 patients requiring intervention. For the entire cohort, median follow-up
      was 37 months (range, 8 to 144 months). There was no statistically significant
      difference among the groups in the number of patients requiring reintervention.
      The overall esophagectomy rate was only 2%. However, there was a significantly
      higher (p = 0.02) esophagectomy rate in the severely dilated patients.
      CONCLUSIONS: The degree of esophageal dilatation associated with achalasia does
      not influence the success of an esophagomyotomy. Of the entire patient population
      in this study, only 6 patients required an esophagectomy. The majority of
      patients with the most severely dilated esophagus did not require an
      esophagectomy. Esophagomyotomy should be the first treatment option for patients
      with achalasia no matter what the degree of esophageal dilatation.

PMID- 19379906
TI  - Positron emission tomography-computed tomography in predicting locoregional
      invasion in esophageal squamous cell carcinoma.
AB  - BACKGROUND: In order to clarify the role of positron emission tomography-computed
      tomography (PET/CT) in thoracic esophageal squamous cell carcinoma we
      investigated its value in predicting locoregional invasion. METHODS: Forty-five
      patients receiving curative esophagectomy and lymph node dissection were
      included. The relationship between PET/CT findings and pathology results were
      studied. Correlation between nodal uptake and the modified lymph node staging,
      which is based on number of involved nodes (N0 = no nodes; N1 = 1 to 3 nodes; N2
      = more than 3 nodes), was evaluated. RESULTS: The mean maximal standardized
      uptake value (SUV(max)) was 5.09 +/- 4.00 in T1, 14.17 +/- 2.46 in T2, 13.32 +/-
      3.96 in T3, and 10.37 +/- 1.94 in T4 primary tumor. The SUV(max) was
      significantly lower in stage T1 tumors than in stage T2 and T3 tumors. For
      regional nodal involvement, PET/CT findings significantly correlated with
      pathology results. However, the sensitivity, specificity, and accuracy of PET/CT
      were only 57.1%, 83.3%, and 71.1%, respectively, and even lower for detecting
      nonregional lymph node metastasis. When stratified by the modified staging
      system, the mean SUV(max) was 0.64 +/- 1.60 in N0, 1.43 +/- 2.08 in N1, and 4.67
      +/- 4.32 in N2 regional lymph node metastases, and was significantly higher in
      patients with N2 metastasis than in patients with N0 and N1 metastases.
      CONCLUSIONS: Locoregional invasion in esophageal cancer can be predicted by
      PET/CT. The SUV(max) of the primary tumor helped identify T1 tumor, and the
      SUV(max) of the regional lymph nodes correlated with the severity of nodal
      involvement.

PMID- 19379907
TI  - Surgical resection of esophageal gastrointestinal stromal tumors.
AB  - BACKGROUND: Due to the rarity of esophageal gastrointestinal stromal tumors
      (GISTs), their clinical course and treatment are poorly understood. We have
      assessed our experience in the diagnosis and management of esophageal GISTs.
      METHODS: We performed a retrospective chart review of patients diagnosed with
      esophageal GISTs who underwent surgical resection. RESULTS: We identified 7
      patients (6 males and 1 female) who underwent surgical procedures due to
      esophageal GISTs between 2001 and 2003; their median age was 46 years (range, 39
      to 68 years). Four patients presented with dysphagia. Two patients were diagnosed
      with GIST by endoscopic biopsy before surgery. Five patients underwent
      enucleation, and two underwent esophagectomy. All tumors were resected completely
      and no patient received perioperative imatinib therapy. Median postoperative
      follow-up was 4.4 years (range, 2.2 to 7.0 years), during which two patients were
      diagnosed with recurrences. CONCLUSIONS: Esophageal GIST is a rare disease, and
      complete surgical resection is the standard treatment. Regular follow-up is
      needed even if resection is complete and negative margins are achieved.

PMID- 19379908
TI  - Invited commentary.

PMID- 19379909
TI  - Complete right atrial ablation with bipolar radiofrequency.
AB  - PURPOSE: Although it is deemed important, right atrial ablation is not considered
      feasible with bipolar radiofrequency alone. Normally, unipolar devices are used
      to complete the tricuspid connecting lines. We describe a simple technique to
      achieve a complete maze-like set of right ablations using a standard bipolar
      radiofrequency device. DESCRIPTION: Thirty-four patients underwent concomitant
      ablation with a right set of lines performed using bipolar radiofrequency only.
      The epicardium adjacent to the right atriotomy was entered and after separating
      the sulcus fat from the atrial wall, the deepest portion of the atrioventricular
      groove was developed bluntly with the scissors down to the tricuspid annulus. The
      tricuspid connecting lines were then performed with bipolar radiofrequency in an
      endo-epicardial fashion. EVALUATION: No ablation-related complications occurred.
      No patient died. Three patients required pacemaker implantation. At a mean follow
      up of 8 +/- 5, 85% of the patients were free from arrhythmias. At 6 months 20 of
      24 patients (83%) were in stable sinus rhythm. CONCLUSIONS: All the maze III
      right atrial ablations can be performed using a bipolar radiofrequency device
      alone. The procedure is safe and easily reproducible on a regular basis.

PMID- 19379910
TI  - Implementation of real-time ultrasound in a thoracic surgery practice.
AB  - PURPOSE: The purpose of this study was to implement real-time transthoracic
      ultrasound in a thoracic surgery and lung transplant practice. DESCRIPTION:
      Ultrasound units that are light, small, robust, and portable are now available.
      Obstacles to use include demarcation issues between specialties, training, and a
      perception that basic ultrasound may be difficult to use. The experience of
      implementing this is described. EVALUATION: After a training period, 62 studies
      were performed in 4 months. Patients and clinicians gave positive feedback. The
      learning time was short, and with ultrasonic guidance, all interventional
      procedures were successful at the first attempt, without any complications.
      CONCLUSIONS: Basic transthoracic ultrasound was found to be easy to learn and use
      by thoracic surgeons, fellows, and specialist nurses. Patients were appreciative.
      Real-time use may have genuine advantages to patient care.

PMID- 19379911
TI  - Endograft collapse after thoracic stent-graft repair for traumatic rupture.
AB  - Endovascular stent grafting has emerged as a new strategy for repair of traumatic
      aortic disruptions; however, this technique is not without complications. In this
      report, we describe a case of endograft collapse after a traumatic aortic
      rupture.

PMID- 19379912
TI  - Alternative approach for endovascular treatment of aortic aneurysms.
AB  - Endovascular treatment of thoracic aortic aneurysms is limited in patients with
      small or calcified femoral arteries, with the most serious complication being
      rupture at the insertion site or distal sections of the artery. To overcome this,
      an iliac conduit is normally created by surgical exposure. We used an original
      access in a patient with a thoracoabdominal aortic aneurysm and narrow femoral
      artery to introduce the endovascular prosthesis directly into the surgically
      exposed iliac artery by a small laparotomy and abdominal wall tunnel without
      iliac conduit. The endoprosthesis was easily implanted, and complete hemostasis
      was achieved with minimal blood loss.

PMID- 19379913
TI  - Aortic valve infective endocarditis: could multi-detector CT scan be proposed for
      routine screening of concomitant coronary artery disease before surgery?
AB  - Usefulness of the coronary artery study has been questioned in patients with
      infective valve endocarditis. Fatal events are reported in the literature due to
      embolization of endocarditic vegetations during cardiac catheterization. For this
      reason, many authors do not recommend preoperative invasive coronary studies in
      these patients. We report the case of a 56-year-old patient with prosthetic valve
      endocarditis with vegetations, and concomitant risk factors for coronary disease.
      We did preoperative coronary screening using multi-detector computed tomographic
      scan imaging, which may be useful for noninvasive imaging of the coronary
      arteries in these patients with high risk of embolization.

PMID- 19379914
TI  - Severe calcified saccular pulmonary artery aneurysm.
AB  - Pulmonary artery aneurysm is a very rare entity. Severe calcified saccular
      pulmonary artery aneurysm is not reported in the literature. A 19-year-old man
      with a severe calcified saccular pulmonary artery aneurysm is described.

PMID- 19379915
TI  - Diagnostic and surgical issues in emergency presentation of a pelvic leiomyoma in
      the right heart.
AB  - A computed tomography scan in a 43-year-old woman with a nonsignificant previous
      medical history demonstrated an inferior caval mass prolapsing through the right
      atrium and the tricuspid valve. The mass was misdiagnosed as a thrombus-in
      transit, and heparin was started. The clinical picture suddenly evolved into
      cardiogenic shock, and the patient underwent an emergency resection of the
      intracardiac portion of the mass. Macroscopic and microscopic features were
      consistent with leiomyoma. In the presence of an inferior caval mass, historical
      elements and computed tomography imaging that do not corroborate the hypothesis
      of caval thrombosis should raise the suspicion of intracaval tumor originating
      from an abdominal or pelvic organ. The preferred treatment strategy is an
      elective combined thoracic and abdominal resection.

PMID- 19379916
TI  - Epicardial electrical isolation of the right atrial appendage on the beating
      heart with an infrared coagulator.
AB  - To determine the clinical efficacy of application of infrared energy to the
      beating heart as a means of creating electrical blocks, an original infrared
      coagulator (KIRC-119; Phomec Inc, Tokyo, Japan) was applied to the atrium of a
      patient with atrial fibrillation. A postoperative electrophysiologic study was
      performed to confirm its efficacy. The coagulator was applied epicardially to the
      beating heart concomitant with an on-pump beating heart coronary artery bypass
      graft procedure. Sinus rhythm was restored during the operation, and the
      electrophysiologic study revealed that a bidirectional block had been created on
      the right atrial appendage. The infrared coagulator may facilitate performance of
      the epicardial Maze procedure on the beating heart.

PMID- 19379917
TI  - Spontaneous chylopericardium: delineation of the underlying anatomic pathology by
      CT lymphangiography.
AB  - Primary isolated chylopericardium is a rare condition with little known cause.
      This is the case of a 22-year-old woman in whom idiopathic chylopericardium
      developed. A lymphangiogram followed by a computed tomographic scan demonstrated
      occlusion of the thoracic duct and multiple lymphatic collaterals abutting the
      pericardial sac. Thoracic duct ligation resulted in the complete cure of the
      patient's condition. We theorized that the development of the pathologic
      lymphatic ducts in close proximity to the pericardium resulted in the development
      of the slowly accumulating chylopericardium.

PMID- 19379918
TI  - Constrictive pericarditis presenting as a calcified anterior cardiac mass.
AB  - Constrictive pericarditis is an infrequent disorder. We report the case of a 52
      year-old man with constrictive pericarditis with an uncommon anterior associated
      pericardial mass. Upon diagnosis of constrictive pericarditis, the patient
      underwent pericardectomy and resection of the mass. He is well 6 months
      postoperatively, with complete resolution of his heart failure symptoms.

PMID- 19379919
TI  - Total anomalous systemic venous drainage to the left atrium.
AB  - We present an unusual case of total anomalous systemic venous drainage in which
      the right superior vena cava, persistent left superior vena cava, inferior vena
      cava, and coronary sinus were present and unusually connected to the left atrium.
      Successful surgical correction was achieved, and the patient's recovery was
      uneventful. Various types of total anomalous systemic venous drainage are
      discussed, and classification of total anomalous systemic venous drainage is made
      under the consideration of creation of cardiopulmonary bypass.

PMID- 19379920
TI  - Peritoneoatrial shunting for intractable chylous ascites complicating thoracic
      duct ligation.
AB  - Thoracic duct ligation for chylothorax is considered a safe and efficient
      procedure. However, we observed two cases that were complicated by intractable
      chylous ascites. Refractory chylous ascites are usually cured by surgical
      peritoneovenous shunting, but in both patients successful treatment required
      peritoneoatrial shunting. Actually, a peritoneovenous shunt was impossible
      because of extensive venous thrombosis in jugular and superior vena cava in one
      patient and failed because of constrictive pericarditis requiring pericardectomy
      in the other, both underlying diseases also accounting for the thoracic duct
      ligation complications.

PMID- 19379921
TI  - Enucleation of a giant esophageal gastrointestinal stromal tumor.
AB  - Despite development of novel chemotherapy for gastrointestinal stromal tumors
      (GISTs), complete resection remains the gold standard treatment. Because of the
      small number of reported esophageal gastrointestinal stromal tumors, the optimal
      extent of resection is not well defined. We present a case of an 82-year-old man
      with an 11-cm esophageal gastrointestinal stromal tumor who was successfully
      treated with enucleation.

PMID- 19379922
TI  - Skin tube reconstruction for esophageal defect due to postoperative complication.
AB  - The occurrence of esophageal conduit necrosis after esophagectomy in patients
      with esophageal cancer is rare, but it is associated with severe and fatal
      complications, and the subsequent surgical reconstruction required by such
      patients is challenging. We reconstructed the esophagus using a skin tube
      prepared from a myocutaneous flap of the anterior chest wall in a patient whose
      entire thoracic esophagus was missing due to reconstructed conduit necrosis after
      surgery for esophageal cancer. Four years after skin tube reconstruction, the
      patient remains free of cancer recurrence with good oral intake and has resumed
      routine activities. Thus, the skin tube is considered very useful for salvage
      esophageal reconstruction.

PMID- 19379923
TI  - Macrocystic lymphatic malformation in the pulmonary parenchyma.
AB  - We present a young girl with a diffuse, macrocystic lymphatic malformation with
      associated venous dilation involving the left lower pulmonary lobe and
      mediastinum. Recurrent hemoptysis necessitated left lower lobectomy. This is the
      first reported case of a macrocystic lymphatic lesion with venous anomalies
      located within the parenchyma of the lung.

PMID- 19379924
TI  - Pneumocephalus after resection of a lung cancer with posterior chest wall
      involvement.
AB  - Pneumocephalus after resection of intrathoracic tumors is an extremely rare
      event. A delayed presentation of iatrogenic subarachnoid pleural fistula resulted
      in symptomatic pneumocephalus after resection of a locally recurrent T4N0
      nonsmall cell lung cancer involving the chest wall, T2 to T4 rib heads, and
      intercostal vertebral foramina. Progressive neurologic decline was noted 3 weeks
      after discharge. Computed tomography of the head and chest confirmed the presence
      of an apical pleural space, thoracic subarachnoid air, and pneumocephalus.
      Immediate clinical improvement followed chest tube decompression of the pleural
      space.

PMID- 19379925
TI  - Successful treatment of multi-drug resistant tuberculosis by double lung
      transplantation.
AB  - A 24-year-old man suffering from end-stage, multi-drug, resistant tuberculosis
      and right heart failure underwent bilateral, single-lung transplantation with
      extracorporeal membrane oxygenator support. He was successfully weaned and
      discharged from the hospital 30 days later. Sputum cultures have been negative
      for tuberculosis since discharge, and for almost 2 years thereafter. Anti
      tuberculosis medication was discontinued 4 months postoperatively.

PMID- 19379926
TI  - Adjunctive use of superoxidized solution in chest wall necrotizing soft tissue
      infection.
AB  - A 39-year-old Indian man presented with necrotizing soft tissue infection of his
      right forearm and previously undiagnosed diabetes mellitus. The infection
      progressively worsened to involve his right lateral chest wall despite multiple
      debridements and systemic antibiotics. His right arm was eventually
      disarticulated along with wide debridement of the surrounding tissue. Aggressive
      wound debridement, mechanical scrubbing, and irrigation were then initiated every
      8 hours. A superoxidized solution was later introduced as a wound irrigant and
      dressing agent. The large defect was suitable for split-thickness skin grafting
      after 16 days of a strict wound management routine with the superoxidized
      solution.

PMID- 19379927
TI  - Obliteration of empyema space by vascularized anterolateral thigh flaps.
AB  - Closure of the fistula and an appropriate choice of obliterating agents are
      crucial for the treatment of empyema with bronchopleural fistula. The choice of
      the material to be used for obliteration of the pleural space is a difficult one
      in some patients, such as those with empyema, developing after omentectomy,
      laparotomy, posterolateral thoracotomy, and so forth. The use of free
      anterolateral thigh flaps for obliteration of the pleural space generally needs a
      satisfactory vascular network around the thorax. We report two successfully
      treated cases of empyema with bronchial fistula, which were otherwise difficult
      to manage, in which a free anterolateral thigh musculocutaneous flap anastomosed
      to the superior thyroid vessels used to obliterate the pleural space.

PMID- 19379928
TI  - Intracardiac invasive thymoma presenting as superior vena cava syndrome.
AB  - A case of invasive thymoma with intra-caval and intracardiac extension presenting
      as superior vena cava syndrome is reported. The tumor is excised on
      cardiopulmonary bypass, and superior vena cava is bypassed using a Dacron graft
      (DuPont, Wilmington, DE). Five-year follow-up of the patient showed a patent
      graft.

PMID- 19379929
TI  - Unruptured sinus of Valsalva aneurysm suspected to be a cardiac tumor.

PMID- 19379930
TI  - Perforated esophagus or large diverticulum?

PMID- 19379931
TI  - Severe tracheal compression due to a seroma: a rare cause of respiratory
      insufficiency after a modified Blalock-Taussig shunt.

PMID- 19379932
TI  - Arterial air embolism: a rare but life-threatening complication of percutaneous
      needle biopsy of the lung.

PMID- 19379933
TI  - Use of an inexpensive blue band during ventricular assist device and total
      artificial heart placement facilitates and expedites explantation during heart
      transplant.
AB  - Ventricular assist devices and total artificial hearts are now being used
      routinely as a bridge to heart transplantation. Reoperation is often weeks to
      months from implantation. Difficulty dissecting mediastinal and cardiac
      structures is often encountered due to adhesion formation that prolongs operative
      time. A temporary, flexible, rectangular-shaped polyisoprene blue band is used to
      encircle major vascular structures. We have found that this facilitates
      identification, reduces adhesion formation, and expedites device removal at the
      time of heart transplantation.

PMID- 19379934
TI  - Building a new annulus: a technique for mitral valve replacement in heavily
      calcified annulus.
AB  - We describe the rationale, methodology, and our preliminary experience with a new
      surgical technique for mitral valve replacement in patients with severe
      calcification of the mitral annulus in which the conventional techniques can not
      be applied. In contrast with other procedures published in the literature for
      these patients, in which the placement of the prosthesis is supra-annular, we
      plicate both mitral leaflets and the atrial wall creating a new annulus that
      allows the intra-annular placement of the prosthesis.

PMID- 19379935
TI  - A novel side graft holder for coronary artery bypass grafting.
AB  - We describe the construction and use of a novel side graft holder for coronary
      artery bypass grafting. The device is a hammer head-shaped clip used to hold the
      graft side securely but atraumatically during sequential or composite graft
      anastomosis. The side graft holder provides gentle stabilization and excellent
      visualization of the side of the graft without causing graft injury.

PMID- 19379936
TI  - Extrapleural pneumonectomy with reconstruction of diaphragm and pericardium using
      autologous materials.
AB  - The procedures and results for extrapleural pneumonectomy through a lower door
      open thoracotomy with reconstruction of the diaphragm and the pericardium using a
      reversed latissimus dorsi muscle flap and a fascia lata graft, respectively, for
      the treatment of malignant pleural mesothelioma are reported. A posterolateral
      thoracotomy was extended along the anterior costal arch with cutting of the sixth
      to ninth costal cartilages. Defects of the diaphragm and the pericardium were
      reconstructed using reversed latissimus dorsi muscle flaps and fascia lata
      grafts, respectively. We conducted this procedure for seven patients with
      malignant pleural mesothelioma, with successful outcome.

PMID- 19379937
TI  - Heparin-induced thrombocytopenia in patients with ventricular assist devices: are
      new prevention strategies required?
AB  - Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating
      antiplatelet factor 4/heparin antibodies. However, clinical HIT (thrombocytopenia
      or thrombosis, or both) develops in only a minority of patients who form
      antibodies. It is difficult to distinguish HIT from non-HIT thrombocytopenia in
      patients after ventricular assist device (VAD) implantation. Further, the risks
      of heparin-induced immunization and clinical HIT approach 65% and 10%,
      respectively, in this patient population, with a particularly high risk of
      cerebrovascular ischemia/infarction. Given the apparent high risk of HIT and its
      complications, and the diagnostic challenges, we suggest that the VAD patient
      population be evaluated using alternative, nonheparin agents for routine
      postimplantation anticoagulation.

PMID- 19379938
TI  - Adjuvant radiotherapy for thymic epithelial tumors: a systematic review and meta
      analysis.
AB  - Adjuvant radiotherapy after complete resection of localized, invasive thymic
      epithelial tumors is considered by many to be the standard of care, despite
      little supporting literature. We hypothesized that individual studies may lack
      statistical power to demonstrate a reduction in recurrence with this approach,
      but meta-analysis of published data may allow for more adequate statistical
      evaluation. Analysis of data from 592 patients with completely resected stage II
      or III thymic epithelial tumors, however, revealed no statistically significant
      reduction in recurrence after adjuvant radiotherapy (odds ratio 1.05; 95%
      confidence interval: 0.63 to 1.75; p = 0.840). Additionally, the majority of
      publications suggest that the most common sites of recurrence are the lung,
      pleura, and diaphragm, even when incompletely resected patients are included.

PMID- 19379940
TI  - Behcet's inflammatory vessels for cannulation in inflammatory aortic repair.

PMID- 19379942
TI  - Technique of cannulation and body perfusion during aortic arch repair.

PMID- 19379944
TI  - Intraluminal shunts at off-pump surgery: friend or foe?

PMID- 19379945
TI  - Unprotected left main coronary artery stenting versus coronary artery bypass
      graft surgery.

PMID- 19379947
TI  - Angiotensin-converting enzyme inhibitors and risk of acute kidney injury after
      cardiac surgery.

PMID- 19379950
TI  - CMS standards in reviewing low-volume cardiac transplant centers.

PMID- 19379951
TI  - New research on medically unexplained symptoms--much remains to be done before
      DSM V and ICD-10 can provide a satisfactory new classification.

PMID- 19379953
TI  - The outcome of medically unexplained symptoms--will DSM-V improve on DSM-IV
      somatoform disorders?

PMID- 19379952
TI  - Medically unexplained symptoms, somatisation disorder and hypochondriasis: course
      and prognosis. A systematic review.
AB  - OBJECTIVE: To study the course of medically unexplained symptoms (MUS),
      somatisation disorder, and hypochondriasis, and related prognostic factors.
      Knowledge of prognostic factors in patients presenting persistent MUS might
      improve our understanding of the naturalistic course and the identification of
      patients with a high risk of a chronic course. METHODS: A comprehensive search of
      Medline, PsycInfo, CINAHL, and EMBASE was performed to select studies focusing on
      patients with MUS, somatisation disorder, and hypochondriasis, and assessing
      prognostic factors. Studies focusing on patients with single-symptom unexplained
      disorder or distinctive functional somatic syndromes were excluded. A best
      evidence synthesis for the interpretation of results was used. RESULTS: Only six
      studies on MUS, six studies on hypochondriasis, and one study on abridged
      somatisation could be included. Approximately 50% to 75% of the patients with MUS
      improve, whereas 10% to 30% of patients with MUS deteriorate. In patients with
      hypochondriasis, recovery rates vary between 30% and 50%. In studies on MUS and
      hypochondriasis, we found some evidence that the number of somatic symptoms at
      baseline influences the course of these conditions. Furthermore, the seriousness
      of the condition at baseline seemed to influence the prognosis. Comorbid anxiety
      and depression do not seem to predict the course of hypochondriasis. CONCLUSIONS:
      Due to the limited numbers of studies and their high heterogeneity, there is a
      lack of rigorous empirical evidence to identify relevant prognostic factors in
      patients presenting persistent MUS. However, it seems that a more serious
      condition at baseline is associated with a worse outcome.

PMID- 19379954
TI  - The role of physical injury in motor and sensory conversion symptoms: a
      systematic and narrative review.
AB  - OBJECTIVES: Conversion symptoms are currently conceptualized as physical symptoms
      induced by psychological trauma, conflict, or stress. Historical accounts also
      included physical injury as an important precipitant. We aimed to determine (a)
      the frequency of reported physical injury prior to onset in published studies of
      patients with motor or sensory conversion symptoms and (b) the clinical
      characteristics of patients in whom onset was associated with physical injury.
      METHODS: Firstly, we employed a systematic review of all reports of adults with
      motor or sensory conversion symptoms published between 1965 and 2005. Secondly,
      we used a narrative review of the literature on this topic, especially possible
      mechanisms. RESULTS: A total of 133 eligible studies, which recorded
      precipitating factors, including 869 patients, were found. Physical injury prior
      to symptom onset was reported in 324 patients (37%). Clinical features associated
      with physical injury included younger age, weakness (vs. movement disorder),
      paraparesis (vs. hemiparesis), and neurological versus psychiatric study
      settings. CONCLUSIONS: Despite the current dominance of a psychological view of
      conversion symptoms, physical injury prior to onset has been frequently reported
      in papers published since 1965. While the data are of low quality, they
      nevertheless suggest that physical trauma has a role in many patients in the
      onset of motor and sensory conversion symptoms. We discuss possible mechanisms
      for this association.

PMID- 19379955
TI  - Effects of placebo interventions on gastric motility and general autonomic
      activity.
AB  - OBJECTIVE: The study aimed to investigate placebo effects on gastric motility and
      to examine possible autonomic mediating mechanisms. METHODS: Eighteen healthy
      volunteers received a placebo pill on three occasions together with the verbal
      suggestion that it would stimulate, relax, or not affect gastric activity.
      Electrogastrogram, electrocardiogram, and electrodermal activity recordings were
      conducted for 30 min prior to and following intervention. RESULTS: Dominant
      frequency of the gastric slow wave decreased in the stimulant condition, and
      increased in the relaxant condition, the difference among conditions being
      significant. No differential effects of the interventions on cardiac interbeat
      intervals, heart rate variability, and skin conductance levels were observed.
      CONCLUSION: Stomach relaxant and stimulant placebo interventions modulated
      gastric motility independently from changes in general autonomic activity.

PMID- 19379956
TI  - Hypervigilance in irritable bowel syndrome compared with organic gastrointestinal
      disease.
AB  - OBJECTIVE: Irritable bowel syndrome (IBS) patients are suggested to selectively
      attend to gastrointestinal (GI) sensations compared with healthy controls.
      However, it remains unclear whether there are differences between IBS and other
      chronic GI disorders. We aimed to evaluate the presence of hypervigilance towards
      the GI tract in IBS compared with patients with organic GI diseases. METHODS: We
      included 36 IBS patients and 40 age- and gender-matched patients with organic GI
      disease. They completed the Hospital Anxiety and Depression Scale (HADS) and
      underwent three tests: (1) word association-write down as many words as possible
      representing signs of disease; (2) word recognition (tachistoscope)-four
      categories of words (positive affects, non-GI symptoms, GI symptoms, negative
      affects) displayed for increasing time until identified; (3) word recollection
      memorize words (10 GI symptoms, 10 positive affects, 10 negative affects).
      RESULTS: The word-association task did not show group differences. IBS patients
      were significantly faster than organic GI patients at recognizing words
      representing GI symptoms (21 vs. 26 ms; P=.04) and negative affects (27 vs. 34
      ms; P=.03), but also tended to be faster at recognizing positive affects (24 vs.
      29 ms; P=.08) and non-GI symptoms (22 vs. 27 ms; P=.2). Both groups remembered a
      similar number of words, but IBS patients tended to recall more incorrect GI
      words than organic patients (1.3 vs. 1.0; P=.06). There were no group differences
      in HADS scores. CONCLUSION: Compared to patients with organic GI disease, IBS
      patients seem to be hypervigilant for information regarding GI sensations and
      maybe also negative information.

PMID- 19379957
TI  - Attention bias and sensitization in chemical sensitivity.
AB  - OBJECTIVE: We investigated whether persons with self-reported chemical
      sensitivity (CS) have an attention bias and enhanced sensitization to chemical
      exposure. METHODS: Chemosomatosensory, olfactory, and auditory event-related
      potentials (ERPs) were recorded from 21 CS subjects and 17 controls in attend and
      ignore conditions. Reaction times (RTs) and magnitude estimations of perceived
      intensity were collected in the attend condition. ERPs were averaged over
      attention conditions and during the first/second part of the testing. RESULTS:
      ERP patterns indicated that CS subjects did not habituate to the same extent as
      the controls and had difficulties ignoring the chemical exposure. CS subjects had
      faster overall RT, and the perceived intensities for the chemosomatosensory
      stimuli did not decrease with time in the CS group, which was the case for the
      controls. CONCLUSIONS: These results indicating attention bias and enhanced
      sensitization in CS suggest alterations in central, cognitive responses to
      chemical exposure.

PMID- 19379958
TI  - Dizziness: anxiety, health care utilization and health behavior--results from a
      representative German community survey.
AB  - BACKGROUND: Due to the lack of epidemiological data on the relation of dizziness
      and anxiety, we investigated the prevalence of dizziness and anxiety in a
      representative sample of the German population. We explored the consequences of
      comorbid anxiety for emotional distress, functional impairment, health care
      utilization, and health behavior in dizziness. METHODS: By the end of 2006, we
      surveyed a total of 1287 persons between 14 and 90 years of age in their homes by
      trained interviewers with standardized self-rating questionnaires on anxiety
      (Patient Health Questionnaire, Generalized Anxiety Disorder Scale, Mini-Social
      Phobia Inventory) and dizziness (Vertigo Symptom Scale). The sample was
      representative for the German population in terms of age, sex, and education.
      RESULTS: Symptoms of dizziness were reported by 15.8% of the participants. Of the
      participants with dizziness, 28.3% reported symptoms of at least one anxiety
      disorder (generalized anxiety, social phobia, panic). Persons with dizziness
      reported more somatic problems such as hypertension, migraine, diabetes, etc.
      Comorbid anxiety was associated with increased health care use and impairment.
      CONCLUSION: Dizziness is a highly prevalent symptom in the general population. A
      subgroup with comorbid anxiety is characterized by an increased subjective
      impairment and health care utilization due to their dizziness. Because treatment
      options for distinct neurotologic disorders are also known to reduce
      psychological symptoms, and in order to avoid unnecessary medical treatment,
      early neurologic and psychiatric/psychotherapeutic referral may be indicated.

PMID- 19379959
TI  - Alexithymia in fibromyalgia syndrome: associations with ongoing pain,
      experimental pain sensitivity and illness behavior.
AB  - OBJECTIVE: Alexithymia, a lack of emotional awareness, is common in chronic pain
      patients. The aim of the study was to investigate the relationship of alexithymia
      to ongoing pain, experimental pain sensitivity, and illness behavior in patients
      with chronic musculoskeletal pain. METHODS: Sixty-eight women with fibromyalgia
      (age: average, 43.4 years; range, 19-72 years) completed self-report measures on
      alexithymia (20-Item Toronto Alexithymia Scale), ongoing pain [Visual Analogue
      Scale, Questionario Italiano del Dolore (QUID), Margolis], psychological distress
      (Center for Epidemiology Studies-Depression Scale, State-Trait Anxiety Inventory
      Form Y), and illness behavior (Illness Behavior Questionnaire). Psychophysical
      tests were performed to assess experimental pain sensitivity, including pain
      thresholds for mechanical (von Frey, tender point count) and thermal (heat, cold)
      stimuli, and cold pressor pain threshold and tolerance. RESULTS: Alexithymia
      "difficulty identifying feelings" (DIF) was related to higher ratings of the
      affective-but not the sensory-dimensions of ongoing pain (QUID) and to a lower
      cold pressor pain tolerance, while alexithymia scores were independent of all
      pain thresholds. Multiple regression demonstrated that alexithymia DIF ceased to
      uniquely predict affective ongoing pain when psychological distress or illness
      behavior was separately controlled for. Higher alexithymia DIF scores were
      predictive of hypochondriacal illness behavior, over and above what was explained
      by psychological distress and affective pain. CONCLUSION: Alexithymia is
      associated with increased affective pain and hypochondriacal illness behavior.
      The former relationship is better explained, and possibly mediated, by
      psychological distress and illness behavior. The hypothesis of a generally
      increased sensitivity to unpleasant stimuli in alexithymic chronic pain patients
      is not supported by the data.

PMID- 19379960
TI  - How are memory complaints in functional memory disorder related to measures of
      affect, metamemory and cognition?
AB  - OBJECTIVE: Memory complaints are a common finding in outpatients, especially in
      psychosomatic and neurological practice. In a substantial group of patients
      persistent memory complaints are found in the absence of abnormal
      neuropsychology. Different labels such as "functional memory complaint" have been
      suggested for this phenomenon. We characterise a group of patients with such
      memory complaints, which we termed functional memory disorder (FMD). The aim of
      the present study is to describe patients with FMD. METHODS: Thirty-nine patients
      with FMD were compared to 38 control subjects. Data were collected on the German
      version of the Rey Auditory Verbal Learning test and the Zahlenverbindungstest
      (cognitive speed), subscales of the Metamemory in Adulthood questionnaire (MIA),
      the Perceived Stress Questionnaire (PSQ), the Global Severity Index (GSI) of the
      Symptom Checklist, the Beck Depression Inventory (BDI), and other psychological
      questionnaire measures. RESULTS: We found significant group differences on all
      psychological questionnaire measures, with more pathological scores in the
      patient group. GSI and PSQ were the best predictors of memory self-efficacy. MIA
      Memory Self-Efficacy (MSE), MIA-Achievement, and BDI were the best predictors of
      group membership (FMD vs. control group). When MSE was excluded, MIA-Achievement
      and BDI or GSI were the only predictors of group membership. Neuropsychological
      measures predicted neither MSE nor group membership. CONCLUSIONS: Pathological
      scores on measures of metamemory, stress, and depression are typical of FMD. Low
      MSE and a high memory-related achievement motivation seem to be key features of
      FMD. Other important features are increased perceived stress, general
      psychosomatic complaint, and elevated depression scores. Neuropsychological test
      performance is not associated with FMD symptoms.

PMID- 19379961
TI  - The relationship between fatigue and psychiatric disorders: evidence for the
      concept of neurasthenia.
AB  - OBJECTIVE: Fatigue and psychiatric disorders frequently occur comorbidly and
      share similar phenomenological features. There has been debate as to whether
      chronic fatigue, or neurasthenia, should be considered an independent syndrome
      distinct from psychiatric disorders. We aimed to establish whether persistent
      fatigue can occur independently from psychiatric disorders and to test the
      hypothesis that fatigue without comorbid psychiatric symptoms has unique
      premorbid risk factors. We also aimed to investigate the psychological outcome of
      any individuals with fatigue. METHODS: The MRC National Survey of Health and
      Development was used to prospectively follow 5362 participants from birth. A
      sample of nonfatigued individuals without psychiatric disorder was selected at
      age 36 and followed until age 43 years (n=2714). At age 43, the presence of new
      onset fatigue and/or psychiatric disorder was assessed. Information on a number
      of potential premorbid risk factors was collected between ages 0 and 36 years.
      Individuals with fatigue but no comorbid psychiatric disorder were then followed
      up at age 53 years. RESULTS: At age 43 years, 201 (7.4%) participants reported
      significant levels of new onset fatigue in the absence of comorbid psychiatric
      disorder. Despite the absence of case level psychiatric disorder, these
      individuals did report increased levels of some psychological symptoms. Excessive
      childhood energy (adjusted OR 2.63, 95% CI 1.55-4.48, P<.001) and being
      overweight at age 36 (adjusted OR 1.62, 95% CI 1.05-2.49, P=.03) were specific
      risk factors for fatigue without psychiatric disorder but not fatigue with
      comorbid psychiatric illness. Neuroticism was a risk factor for fatigue both with
      and without comorbid psychiatric disorder. Negative life events and a family
      history of psychiatric illness were only risk factors for fatigue when it
      occurred comorbidly with psychiatric illness. CONCLUSIONS: A significant
      proportion of the adult population will suffer from fatigue without comorbid
      psychiatric disorder. While fatigue and psychiatric disorders share some risk
      factors, excessive energy in childhood and being overweight as an adult appear to
      be specific risk factors for fatigue. Our results confirm the significant overlap
      between fatigue and psychiatric disorders, while also providing evidence for
      neurasthenia as a separate diagnosis.

PMID- 19379962
TI  - The Soma Assessment Interview: new parent interview on functional somatic
      symptoms in children.
AB  - OBJECTIVE: Medically unexplained or functional somatic symptoms (FSS) in children
      constitute a major clinical problem. Epidemiological studies of this phenomenon
      are, however, hampered by a lack of good standardized measures. The objective of
      this study was therefore to (1) develop a parent-report measure of FSS in
      children aged 5-10 years and (2) perform an initial validation. METHODS: A parent
      interview, the Soma Assessment Interview (SAI), for FSS detection in young
      children was developed for lay interviewers with subsequent clinical assessment.
      A preliminary validation was based on interview tests of the parents of 54
      children with well-defined physical disease, 59 with likely functional disorder
      and 105 from the community. Independent measures of the somatic complaints were
      completed before the interview, and children from the clinical samples were also
      assigned independent FSS diagnoses based on medical record review. RESULTS: The
      Kappa value for two clinical assessors' agreement on FSS recognition was 0.86.
      Good discrimination was obtained between a community sample and a clinical sample
      with an expected high prevalence of FSS. In the former convergent validity with
      independent measures of somatic complaints was found. In the latter substantial
      agreement (89%) appeared between a medical record diagnosis of FSS and SAI
      detection of FSS. CONCLUSION: The SAI offers comprehensive description of FSS in
      young children in population-based studies and may also prove useful in clinical
      settings. It is readily accepted and relatively quickly completed, and
      preliminary assessment of its validity is promising.

PMID- 19379963
TI  - Headache sufferers' drawings reflect distress, disability and illness
      perceptions.
AB  - OBJECTIVE: Drawings have recently been used with patients with heart problems to
      assess their perceptions of their illness. This study aimed to investigate
      whether drawings could be a useful way to assess headache patients' perceptions
      of their headaches and their reactions. METHODS: In a cross-sectional study, 65
      university students who experienced persistent headaches were asked to draw a
      picture of how their headaches usually affected them. Drawings were assessed in
      three ways: they were categorized based on content; their size was measured; and
      image analysis software assessed their darkness. Associations between drawings,
      illness perceptions, mood, and health outcomes were assessed. RESULTS: Twenty
      seven people drew an external force to the head and these people had greater
      ratings of average pain and were more likely to attribute their headache to
      stress. Darker drawings were associated with greater emotional distress and lower
      vitality. Larger drawing size was associated with perceptions of worse
      consequences, worse symptoms, worse emotional representations, lower vitality,
      higher pain, and more days of restricted activity, lower happiness, and higher
      sadness. CONCLUSION: Drawings offer an additional way to assess peoples'
      experience of their headaches and reflect illness perceptions and distress.
      People draw how they see themselves experiencing their headache and often include
      expressions and reactions. The inclusion of force to the head, darker drawings,
      and larger drawings are associated with worse perceptions of the headache and
      higher pain. Drawings may be a useful way for clinicians to understand patients'
      experience of pain.

PMID- 19379964
TI  - Relations between cardiothoracic surgeons and industry.

PMID- 19379965
TI  - Treatment selection for coronary artery disease: The collision of a belief system
      with evidence.

PMID- 19379966
TI  - Factors affecting interest in cardiothoracic surgery: Survey of North American
      general surgery residents.
AB  - BACKGROUND: Applications to cardiothoracic surgery (CTS) training programs have
      declined precipitously. The viewpoints of potential applicants, general surgery
      residents, have not yet been assessed. Their perceptions are crucial to
      understanding the cause and formulating appropriate changes in our educational
      system. METHODS: An initial survey instrument was content-validated, and the
      final instrument was distributed electronically between March 24 and May 2, 2008
      through 251 general surgery program directors to all Accreditation Council for
      Graduate Medical Education-accredited general surgery residents (7508). RESULTS:
      The response rate was 29% (2153 residents; 89% programs). Respondent's
      demographics matched existing data; 6% were committed to CTS, and 26% reported
      prior or current interest in CTS. Interest waned after postgraduate year 3.
      Interest correlated with CTS rotation duration. Of the respondents committed to
      CTS, 76% had mentors (71% were cardiothoracic surgeons). CTS had the most
      shortcomings among 9 subspecialties. Job security and availability accounted for
      46% of reported shortcomings (3 to 14 times higher than other subspecialties).
      Work schedule accounted for 25%. Length of training was not a very important
      factor, although it was identified as an option to increase interest in CTS.
      Residents who were undecided or uninterested in CTS were twice as likely to cite
      the ability to balance work and personal life as important than residents who
      chose CTS. CONCLUSIONS: The dominant concern documented in the survey is job
      security and availability. The importance of mentorship and exposure to CTS
      faculty in promoting interest was also evident. Decision makers should consider
      these findings when planning changes in education and the specialty.

PMID- 19379967
TI  - Regional wall motion abnormalities and scarring in severe functional ischemic
      mitral regurgitation: A pilot cardiovascular magnetic resonance imaging study.
AB  - OBJECTIVES: To relate cardiovascular magnetic resonance-derived segmental wall
      motion and myocardial scarring and determine whether they are associated with
      postoperative mitral regurgitation following coronary artery bypass grafting and
      annuloplasty for severe functional ischemic mitral regurgitation. METHODS: From
      January 2001 to October 2006, 29 patients with grade >or=3+ chronic functional
      ischemic mitral regurgitation were studied using cardiovascular magnetic
      resonance. Wall motion abnormality was graded for 17 standard left ventricular
      myocardial segments (0 = none, 1+ = hypokinesis, 2+ = severe hypokinesis, 3+ =
      akinesis, 4+ = dyskinesis), as was degree of hyperenhancement (scarring).
      Postoperative mitral regurgitation was assessed longitudinally by 71
      transthoracic echocardiograms. RESULTS: Wall motion abnormalities grade >or=2+
      were present in most myocardial segments (median 13). Scar >25% was present in a
      median of 3 segments, and 44% of those were in the territory of the posterior
      papillary muscle. Nearly all segments (95%) with >25% scar had >or=2+ wall motion
      abnormality. Although 90% of patients had no mitral regurgitation at hospital
      discharge, by 6 months, 34% had mitral regurgitation grade >or=2+. There was
      little association between wall motion abnormality and recurrence of mitral
      regurgitation (P > .1). Seventy percent of patients with scar >25% in the
      posterior papillary muscle region exhibited postoperative mitral regurgitation of
      grade >or=2+ by 6 months, compared with 15% with score <or=25% (P = .07).
      CONCLUSIONS: In a pilot study of cardiovascular magnetic resonance imaging in
      severe functional ischemic mitral regurgitation, severity of posterior papillary
      muscle region scarring correlated with decreased segmental wall motion and mitral
      regurgitation early after coronary revascularization and annuloplasty. Routinely
      assessing scar burden may identify patients for whom annuloplasty alone is
      insufficient to eliminate mitral regurgitation.

PMID- 19379969
TI  - Recovery of left ventricular function after surgical correction of mitral
      regurgitation caused by leaflet prolapse.
AB  - OBJECTIVE: Recovery of ventricular function after surgical correction of mitral
      regurgitation is often incomplete. We studied clinical and echocardiographic
      factors influencing return of normal left ventricular ejection fraction after
      mitral valve repair or replacement for mitral regurgitation caused by leaflet
      prolapse. METHODS: We evaluated 1063 patients who had mitral valve repair or
      replacement between January 1, 1980, and December 31, 2000. A total of 2488
      echocardiograms with follow-up ejection fractions were available for analysis.
      RESULTS: Of the patients, 761 were men, 924 had valve repair, and 85% underwent
      surgery during the study's second decade. Compared with patients who had the
      operation in the 1980s, patients who had surgery in the 1990s had significantly
      smaller preoperative left heart dimensions and a 2.4-fold greater likelihood of
      an ejection fraction more than 60% during follow-up. Factors independently
      associated with higher ejection fraction at follow-up included valve repair (vs
      replacement), freedom from preoperative myocardial infarction, operation in the
      1990s, greater preoperative ejection fraction, and smaller left ventricular
      dimensions. Patients with an ejection fraction of less than 50% at discharge were
      3.5-fold less likely to recover normal ejection fraction during long-term follow
      up (P < .001). Patients had a greater likelihood of a follow-up ejection fraction
      more than 60% if preoperative ejection fraction was more than 65% (hazard ratio,
      1.7) or left ventricular end-systolic dimension was less than 36 mm (hazard
      ratio, 2.0). CONCLUSION: Early repair of mitral regurgitation caused by leaflet
      prolapse, before deterioration in left heart size or function, increases the
      likelihood of subsequent normalization of left ventricular ejection fraction.

PMID- 19379970
TI  - Mitral leaflet anatomy revisited.
AB  - OBJECTIVE: The aims of this work were to employ functional imaging capabilities
      of the Visible Heart laboratory and endoscopic visualization of mitral valves in
      perfusion-fixed specimens to better characterize variability in mitral valve
      leaflet anatomy and to provide a method to classify mitral leaflets that varies
      from the current nomenclature. METHODS: We gathered functional endoscopic video
      footage (11 isolated reanimated human hearts) and static endoscopic anatomical
      images (38 perfusion-fixed specimens) of mitral leaflets. Commissure and cleft
      locations were charted using Carpentier's accepted description. RESULTS: All
      hearts had 2 commissures separating anterior and posterior leaflets. "Standard"
      clefts separating P1/P2 were found in 66% of hearts (n = 25), and standard clefts
      separating P2/P3 were present in 71% of hearts (n = 27). "Deviant" clefts
      occurred in each region of the anterior leaflet (A1, A2, A3), and their relative
      occurrences were 5%, 8%, and 13% (n = 2, 3, 5), respectively. Deviant clefts were
      found in posterior leaflets: 13.2% in P1 (n = 5), 32% in P2 (n = 12), and 21% in
      P3 (n = 8). CONCLUSIONS: Humans elicit complex and highly variable mitral valve
      anatomy. We suggest a complementary, yet simple nomenclature to address variation
      in mitral valve anatomy by describing clefts as either standard or deviant and
      locating regions in which they occur (A1 to A3 or P1 to P3).

PMID- 19379971
TI  - Re-creation of a sinuslike graft expansion in Bentall procedure reduces stress at
      the coronary button anastomoses: A finite element study.
AB  - OBJECTIVE: The Bentall procedure is routinely performed using a straight Dacron
      graft coupled with a mechanical or a biologic valve. Creation of coronary ostia
      buttons significantly reduces tension on the coronary anastomoses and
      consequently the incidence of pseudoaneurysm formation. We sought to evaluate if
      the use of a specifically designed graft with a sinuslike root portion that
      bulges out upon pressurization can reduce stress on coronary anastomoses. A
      finite element computer-assisted stress analysis was used to simulate these 2
      different anatomic conditions and to analyze tension in computed tomographic
      scans obtained from patients operated on with either a straight or a "sinus"
      graft. METHODS: Theoretical models of the procedures with finite element computer
      aided design technique were created and tested with the Abaqus Standard Suite,
      verifying the pattern of stress and strain when a uniform pressure of 200 mm Hg
      was applied to the model. Next, using SimpleWare SCanIP technology, computed
      tomographic scans of patients having both procedures were used to obtain finite
      element mesh models. A uniform pressure of 200 mm Hg was then applied, and the
      distribution of stress and strain was analyzed. RESULTS: Von Mises Charts are
      color-coded, computational, 3-dimensional stress-pattern graphics that show that
      stress around the coronary ostia in a standard straight graft model is nearly
      double compared with the model with sinuses (peak stress of 0.4 Mpa for the sinus
      model and 0.7 Mpa for the traditional straight model). In computed tomographic
      scan reconstructions, the stress contour is uniformly distributed in the graft
      with sinuses, and it is highly concentrated around the ostia in the straight
      graft. Accordingly, higher-peak stress values are registered in the straight
      configuration (1.8 MPa for the sinus graft and 2.5 MPa for standard graft).
      CONCLUSION: Even though finite elements technique is necessarily a simplification
      of a real biologic environment, all tests seem to indicate that a standard
      tubular graft gives a higher stress to coronary sutures. Relieving the stress on
      the coronary anastomoses by using a graft with preformed sinuses of Valsalva may
      decrease the incidence of postoperative complications such as bleeding and late
      pseudoaneurysm formation.

PMID- 19379972
TI  - Short- and midterm outcomes of coronary artery bypass surgery performed by
      surgeons in training.
AB  - OBJECTIVE: The effect of training on outcomes in cardiac surgery is poorly
      studied. We aimed to study the results of coronary artery bypass grafting
      procedures performed by surgeons in training across our state with respect to
      short- and midterm postoperative outcomes. METHODS: All coronary artery bypass
      grafting surgeries performed by trainee surgeons between July 2001 and December
      2006 were compared with those performed by consultant surgeons using mandatory
      prospectively collected statewide data. Early mortality; prolonged ventilation or
      intensive care unit stay; return to operating theater for bleeding, stroke,
      myocardial infarction, or renal failure; and 5-year survival were compared using
      propensity score analysis. RESULTS: A total of 7745 surgeries were included in
      this study. Trainees performed 983 (13%) surgeries. Trainee surgeries had longer
      perfusion and crossclamp times. Crude early postoperative outcomes were similar
      between trainee and consultant surgeries. After propensity score adjustment,
      early outcomes remained similar, with the exception of myocardial infarction
      (0.8% in trainee surgeries vs 0.4% in consultant surgeries, P = .046). Adjusted 1
      , 3-, and 5-year survivals were similar between trainee and consultant surgeries:
      95.3% versus 95.5%, 90.8% versus 92.0%, and 86.3% versus 87.1%, respectively.
      CONCLUSION: Coronary artery bypass grafting performed by trainee surgeons within
      a supervised program is safe with acceptable short- and midterm outcomes.

PMID- 19379973
TI  - Arterial revascularization in primary coronary artery bypass grafting: Direct
      comparison of 4 strategies--results of the Stand-in-Y Mammary Study.
AB  - OBJECTIVE: It is unclear (1) whether the use of 2 arterial conduits rather than a
      single conduit in multivessel coronary artery bypass grafting significantly
      improves results despite the concomitant use of saphenous vein grafts and (2)
      whether any among different configurations of composite grafts (left/right
      thoracic arteries and radial artery) offers an advantage over the others.
      METHODS: Eight hundred fifteen patients were randomized to one of 3 different
      strategies of revascularization by using the left thoracic artery plus the right
      thoracic artery or using the left thoracic artery plus the radial artery. Venous
      grafts were used for the remaining targets. Patients randomized to receive 1
      arterial graft served as control subjects. Operative mortality and morbidity were
      comparable among groups. RESULTS: The rate of cerebrovascular complications was
      not statistically lower among patients receiving 2 arterial grafts. At 2 years,
      overall survival was not significantly different among groups (P = .59). Cardiac
      event-free survival was significantly better in patients receiving 2 arterial
      grafts versus control subjects (P < .0001), even among elderly patients (P =
      .022). The 3 investigated strategies using 2 arterial conduits were similar
      concerning early and midterm results. CONCLUSIONS: Revascularization with 2
      arterial conduits offers better midterm event-free survival than a single
      arterial graft, irrespective of which second-choice arterial conduit is used
      (radial artery or right thoracic artery), the simultaneous use of saphenous vein
      grafts, and the patient's age.

PMID- 19379974
TI  - Dimensional analysis of human saphenous vein grafts: Implications for external
      mesh support.
AB  - OBJECTIVE: Constrictive external mesh support of vein grafts was shown to
      mitigate intimal hyperplasia in animal experiments. To determine the degree of
      constriction required for the elimination of dimensional irregularities in
      clinically used vein grafts, a detailed anatomic study of human saphenous veins
      was conducted. METHODS: In 200 consecutive patients having coronary artery bypass
      grafting, harvested saphenous veins (length 34.4 +/- 10.8 cm) were analyzed
      regarding diameter irregularities, side branch distribution, and microstructure.
      RESULTS: The mean outer diameter of surgically distended saphenous veins was 4.2
      +/- 0.6 mm (men, 4.3 +/- 0.6 mm vs women, 3.9 +/- 0.5 mm; P < .0001). Although
      the outer diameter significantly decreased over the initial 18 cm (-7.6%; P <
      .0001), the overall increase between malleolus and thigh was not significant
      (+11.2%). Smaller-diameter veins (<3.5 mm) had more pronounced diameter
      fluctuations than larger veins (31.8% +/- 11.0% vs 21.2% +/- 8.8%; P < .0001),
      with more than 71% of all veins showing caliber changes of more than 20%. There
      was 1 side branch every 5.4 +/- 4.3 cm, with a significantly higher incidence
      between 20 and 32 cm from the malleolus (P < .0001 to distal, P < .0004 to
      proximal). Generally, women had more side branches than men (0.30 +/- 0.15 cm(-1)
      vs 0.25 +/- 0.12 cm(-1); P = .0190). Thick-walled veins (565.7 +/- 138.4 mum) had
      a significantly higher number of large side branches (P < .0001), and thin-walled
      veins (398.7 +/- 123.2 mum) had significantly more small side branches (P <
      .0001). Pronounced intimal thickening ("cushions") was found in 28% of vessels
      (119.8 +/- 28.0 mum vs 40.1 +/- 18.2 mum; P < .0001). CONCLUSION: Although the
      preferential location of side branches may be addressed by the deliberate
      discarding of infragenicular vein segments, a diameter constriction of 27% on
      average would eliminate diameter irregularities in 98% of vein grafts.

PMID- 19379975
TI  - Seven-year results with the St Jude Medical Silzone mechanical prosthesis.
AB  - OBJECTIVE: The Artificial Valve Endocarditis Reduction Trial was stopped on
      January 21, 2000, due to a higher incidence of paraprosthetic leak in the St Jude
      Medical Silzone prosthesis compared with the conventional prosthesis. The
      Artificial Valve Endocarditis Reduction Trial investigators reported the 2-year
      results in 2002. This retrospective study assessed the influence on
      thromboembolism and paraprosthetic leak to 7 years. METHODS: A total of 253
      patients had 254 operations: 80 aortic valve replacements, 139 mitral valve
      replacements, and 35 multiple replacements with placement of Silzone prostheses.
      The mean age was 58.6 years (range 21-84 years, median age 59.8 years), and there
      were 126 women (49.8%) and 74 concomitant procedures (coronary artery bypass
      28.9%). RESULTS: Major paraprosthetic leak (repair, re-replacement, or mortality)
      occurred in 10 of the original procedures after 30 days (3 aortic valve
      replacements, 3 mitral valve replacements, 4 multiple replacements). Nine
      occurrences in 8 patients-5 early (<or=2 years) and 4 late (>2 years)-were
      managed. Seven were managed with definitive re-replacement. One was an early
      nonoperative fatality. There was 1 late fatality after the second late
      paraprosthetic leak reoperation. One of the 10 procedures occurring after 2 years
      had mild to moderate aortic valve replacement paraprosthetic leak managed as an
      incidental re-replacement at the time of correction of supra valvular patch
      stenosis. One additional occurrence, in addition to the 8 patients (<30 days),
      was considered a technical error and not related to the Silzone prosthesis and
      was replaced with a Silzone prosthesis. The linearized rate of paraprosthetic
      leak within the first 2 years of follow-up was 1.3%/patient-year and after 2
      years was 0.4%/patient-year. The linearized occurrence rate for major
      thromboembolism was 0.42%/patient-year for aortic valve replacement and
      1.71%/patient-year for mitral valve replacement. CONCLUSIONS: Paraprosthetic leak
      with the St Jude Medical Silzone prosthesis was managed both during the early
      (<or=2 years) and late (>2years) intervals with re-replacement. Late managed
      events may be manifestations of earlier occurring paraprosthetic leak. Follow-up
      echocardiograms should meet standards of care, 6 to 12 months after surgery and
      at the slightest suspicion of dysfunction. There is no advanced continuing risk
      of the St Jude Medical Silzone prosthesis.

PMID- 19379976
TI  - Surgical volume and outcomes of off-pump coronary artery bypass graft surgery:
      Does it matter?
AB  - OBJECTIVES: Coronary artery bypass grafting performed off-pump has emerged in
      recent years as a less morbid alternative to on-pump bypass grafting. However,
      the impact of hospital volume on the outcomes of off-pump relative to on-pump
      bypass grafting has not been evaluated. METHODS: We conducted a retrospective
      study of patients undergoing off-pump (n = 26,011) and on-pump (n = 99,344)
      coronary artery bypass grafting during 2000 through 2004 in 124 California
      hospitals, using the California Patient Discharge Database. Generalized linear
      mixed models were used to compare in-hospital mortality and postoperative
      complications in patients undergoing on-pump versus off-pump bypass grafting,
      accounting sequentially for differences in patient characteristics and hospital
      level effects. The relative mortality and complication rates for patients
      undergoing on-pump versus off-pump coronary bypass were evaluated across hospital
      volume quartiles. RESULTS: Mean length of stay was lower for patients who
      underwent off-pump compared with on-pump bypass grafting (8.7 vs 9.6 days; P <
      .001), as were unadjusted mortality and complication rates (2.2% vs 3.3%; 10.1%
      vs 11.6%, respectively; P < .001). For hospitals in the highest percent off-pump
      bypass quartile, adjusted mortality and complication rates for patients having
      off-pump bypass were significantly lower than for the on-pump group (odds ratio
      [OR] = 0.50; 95% confidence intervals [CI], 0.41-0.61; OR = 0.73; 95% CI, 0.66
      0.81, respectively; P < .001); by contrast, for hospitals in the lowest percent
      off-pump bypass quartile, mortality and complications were similar in off-pump
      and on-pump groups (OR = 1.10; 95% CI, 0.75-1.63; OR = 0.92; 95% CI, 0.72-1.16,
      respectively; P > .05). CONCLUSIONS: Outcomes were significantly better for off
      pump compared with on-pump coronary artery bypass grafting. Although the benefit
      of off-pump bypass grafting increased as the relative use of the procedure at a
      hospital increased, off-pump bypass grafting can be safely implemented across
      numerous hospitals.

PMID- 19379977
TI  - Valve-sparing and valve-replacing techniques for aortic root replacement in
      patients with Marfan syndrome: Analysis of early outcome.
AB  - OBJECTIVE: A prospective, international registry study was initiated to provide
      contemporary comparative data on short-term clinical outcomes after aortic valve
      sparing and aortic valve-replacing root operations in patients with Marfan
      syndrome. The purpose of this initial report is to describe the study design and
      to compare early outcomes in the first 151 enrolled patients. METHODS: We
      assessed 30-day outcomes in 151 patients who met strict Ghent diagnostic criteria
      for Marfan syndrome and underwent aortic root replacement with either valve
      replacing (n = 46) or valve-sparing techniques (n = 105) at one of 18
      participating centers. In the valve replacement group, a mechanical composite
      valve graft was used in 39 (85%) patients and a bioprosthetic valve in 7 (15%).
      In the valve-sparing group, David V procedures were performed in 57 (54%)
      patients, David I in 38 (36%), David IV in 8 (8%), Florida sleeve in 1 (1%), and
      Yacoub remodeling in 1 (1%). RESULTS: No in-hospital or 30-day deaths occurred.
      Despite longer crossclamp and cardiopulmonary bypass times in the valve-sparing
      group, there were no significant between-group differences in postoperative
      complications. Thirty-day valve-related complications occurred in 2 (4%) patients
      undergoing valve replacement and in 3 (3%) undergoing valve-sparing procedures (P
      = .6). CONCLUSIONS: The analysis of early outcomes revealed that valve-sparing
      techniques were the most common approach to root replacement in patients with
      Marfan syndrome in these centers. The complexity of valve-sparing root
      replacement did not translate into any demonstrable adverse early outcomes.
      Subsequent analysis will compare the 3-year durability of these two surgical
      approaches.

PMID- 19379979
TI  - The complex relationship between pediatric cardiac surgical case volumes and
      mortality rates in a national clinical database.
AB  - OBJECTIVE: We sought to determine the association between pediatric cardiac
      surgical volume and mortality using sophisticated case-mix adjustment and a
      national clinical database. METHODS: Patients 18 years of age or less who had a
      cardiac operation between 2002 and 2006 were identified in the Society of
      Thoracic Surgeons Congenital Heart Surgery Database (32,413 patients from 48
      programs). Programs were grouped by yearly pediatric cardiac surgical volume
      (small, <150; medium, 150-249; large, 250-349; and very large, >or=350 cases per
      year). Logistic regression was used to adjust mortality rates for volume,
      surgical case mix (Aristotle Basic Complexity and Risk Adjustment for Congenital
      Heart Surgery, Version 1 categories), patient risk factors, and year of
      operation. RESULTS: With adjustment for patient-level risk factors and surgical
      case mix, there was an inverse relationship between overall surgical volume as a
      continuous variable and mortality (P = .002). When the data were displayed
      graphically, there appeared to be an inflection point between 200 and 300 cases
      per year. When volume was analyzed as a categorical variable, the relationship
      was most apparent for difficult operations (Aristotle technical difficulty
      component score, >3.0), for which mortality decreased from 14.8% (60/406) at
      small programs to 8.4% (157/1858) at very large programs (P = .02). The same was
      true for the subgroup of patients who underwent Norwood procedures (36.5% [23/63]
      vs 16.9% [81/479], P < .0001). After risk adjustment, all groups performed
      similarly for low-difficulty operations. Conversely, for difficult procedures,
      small programs performed significantly worse. For Norwood procedures, very large
      programs outperformed all other groups. CONCLUSION: There was an inverse
      association between pediatric cardiac surgical volume and mortality that became
      increasingly important as case complexity increased. Although volume was not
      associated with mortality for low-complexity cases, lower-volume programs
      underperformed larger programs as case complexity increased.

PMID- 19379981
TI  - Experimental off-pump transventricular pulmonary valve replacement using a self
      expandable valved stent: A new approach for pulmonary incompetence after repaired
      tetralogy of Fallot?
AB  - OBJECTIVE: Off-pump valve replacement using self-expandable stents is an emerging
      technique for pulmonary valve disease. However, significant limitations are the
      lack of easily available valve substitute to be inserted within the stent and, in
      the setting of repaired tetralogy of Fallot, the existence of huge pulmonary
      trunk. We report the first experimental results of a transventricular approach
      using a decellularized porcine xenograft mounted in a self-expandable stent.
      METHODS: Pulmonary valve replacement was realized in 15 lambs by direct access of
      the infundibulum through a left thoracotomy, combined with pulmonary artery
      banding. Animals were followed by transthoracic echocardiography and, after
      control hemodynamic study, were electively killed either at day 7, month 1, or
      month 4 after implantation. RESULTS: Implantation succeeded in all lambs. Two
      animals died after implantation (1 pneumothorax and 1 endocarditis). Doppler
      echocardiographic follow-up did not show any significant transvalvular gradient
      and showed only mild pulmonary regurgitation. The hemodynamic control before
      termination revealed a systolic pulmonary valve gradient of 18.5 +/- 12.4 mm Hg
      at 1 week (n = 4), 13.5 +/- 10.6 mm Hg at 1 month (n = 4), and 4.3 +/- 4.9 mm Hg
      at 4 months (n = 5). Gross examination demonstrated the presence of connective
      tissue between the valved stent and pulmonary wall, which increased with time.
      CONCLUSION: Fifteen lambs underwent successful deployment of a self-expandable
      valved stent in the pulmonary position using a transventricular approach. This
      technique combined with pulmonary artery banding could be a therapeutic option
      for pulmonary insufficiency after repair of tetralogy of Fallot with a
      transannular patch.

PMID- 19379982
TI  - Right ventricular hypertrophy with early dysfunction: A proteomics study in a
      neonatal model.
AB  - OBJECTIVE: Right ventricular hypertrophy and subsequent dysfunction is common in
      patients with congenital heart defects, but the molecular mechanisms underlying
      change from adaptive hypertrophy to dysfunction remain elusive. We used the novel
      technique of proteomics to characterize protein changes in right ventricular
      myocardium in a neonatal model of right ventricular hypertrophy and early
      dysfunction. METHODS: Twelve neonatal piglets were equally randomized to
      pulmonary artery banding (PAB group), or sham operation (thoracotomy without
      banding). After 4 weeks, right ventricular morphology and function were assessed
      in vivo using magnetic resonance imaging. Animals were humanely killed.
      Proteomics of right ventricular myocardium was performed. Purified right
      ventricular proteins were separated by 2-dimensional difference gel
      electrophoresis using fluorescent cyanine dyes. After gel imaging, software
      analysis revealed protein spots differentially expressed between the 2 groups;
      these spots were excised and identified by mass spectrometry. RESULTS: On
      magnetic resonance imaging, animals with pulmonary artery banding demonstrated
      significant right ventricular hypertrophy, cavity dilatation, and mild systolic
      impairment (right ventricular ejection fraction 39.8% +/- 15% vs 56.7% +/- 10%
      controls; P < .05). Right ventricular free wall mass on harvest confirmed right
      ventricular hypertrophy. Proteomic analysis revealed 18 proteins that were
      significantly differentially expressed: 5 structural proteins, 6 metabolic
      enzymes, 2 stress proteins, and 5 miscellaneous proteins. Expression of calsarcin
      1 and vinculin was increased, as were certain metabolic enzymes, although F(1)
      ATPase beta-chain and heat shock protein 70 decreased. CONCLUSIONS: This is the
      first study characterizing right ventricular protein changes in a large animal
      model specifically capturing the change from compensated to maladaptive
      hypertrophy. These findings can guide future work at elucidating the mechanisms
      in the pathophysiology of neonatal right ventricular hypertrophy and dysfunction.

PMID- 19379983
TI  - Myocardial membrane injury in pediatric cardiac surgery: An animal model.
AB  - OBJECTIVE: Reduced myocardial performance invariably follows pediatric cardiac
      surgery and is manifested by a low cardiac output state in its severest form. The
      role of myocardial membrane proteins in this setting is unknown. Dystrophin and
      dysferlin are involved in membrane integrity, whereas aquaporins selectively
      transport water. These proteins were examined in a model of pediatric cardiac
      surgery, together with a trial of poloxamer 188, which may reduce membrane
      injury. METHODS: Eight lambs were randomized to saline with or without poloxamer
      188. Lambs underwent 2 hours of cardiopulmonary bypass and aortic crossclamping.
      After a further 9 hours of monitoring, the hearts were assessed for water
      content, capillary leak, and protein expression. RESULTS: Dystrophin expression
      was unaffected by ischemia/reperfusion, but dysferlin expression was reduced.
      Aquaporin 1 protein increased after ischemia/reperfusion. Poloxamer 188
      administration was associated with supranormal levels of dystrophin, preservation
      of dysferlin expression, and normalization of aquaporin 1 expression. Poloxamer
      188 was associated with less capillary leak, maintained colloid osmotic pressure,
      and less hemodilution. Poloxamer 188 was associated with an improved hemodynamic
      profile (higher blood pressure, higher venous saturation, and lower lactate),
      although the heart rate tended to be higher. CONCLUSIONS: Changes in protein
      expression within the myocardial membrane were found in a clinically relevant
      model of pediatric cardiac surgery. Indicators of reduced performance, such as
      lower blood pressure and lower oxygen delivery, were lessened in association with
      the administration of the membrane protecting poloxamer 188. Poloxamer 188 was
      also associated with potentially beneficial changes in membrane protein
      expression, reduced capillary leakage, and less hemodilution.

PMID- 19379984
TI  - Factors associated with arch reintervention and growth of the aortic arch after
      coarctation repair in neonates weighing less than 2.5 kg.
AB  - OBJECTIVES: Neonates weighing less than 2.5 kg with aortic coarctation are
      challenging. We sought to find the prevalence of death or aortic arch
      reintervention and their determinants after coarctation repair. We also sought to
      define growth trajectories for postrepair aortic arch dimensions and identify
      factors associated with accelerated longitudinal growth. METHODS: We reviewed
      neonates weighing less than 2.5 kg undergoing coarctation repair between 1993 and
      2004. Competing-risks methods determined time-related prevalences of death, arch
      reintervention, and survival without subsequent reintervention. Mixed regression
      analysis modeled longitudinal growth trajectories of echocardiographically
      derived aortic arch dimensions. RESULTS: Thirty-six neonates underwent
      coarctation repair. Initial repair type was simple end to end (n = 3), extended
      end to end (n = 16), subclavian flap aortoplasty (n = 15), and patch aortoplasty
      (n = 2). Median initial repair age was 11 days (range 2-69 days) and mean weight
      was 2.01 +/- 0.33 kg. Overall 1-year survival was 76%. After 1 year from initial
      repair, 19% had died without subsequent reintervention, 14% underwent arch
      reintervention, and 67% remained alive without arch reintervention. Neonates with
      extended end-to-end repairs had increased transverse aortic arch Z-scores (P =
      .004). Although patients with larger initial transverse aortic arch Z-scores had
      higher scores across all time points (P < .001), neonates with the smallest
      transverse aortic arch Z-scores had accelerated growth trajectories (P < .001).
      Aortic isthmus growth was likewise accelerated in neonates with the smallest
      initial aortic isthmus Z-score (P < .001). CONCLUSIONS: Mortality and arch
      reintervention are common after initial repair of coarctation of the aorta in
      neonates weighing less than 2.5 kg. Catch-up growth of both the transverse arch
      and isthmus occurs after coarctation repair, especially in those with the
      smallest arch parameters, and may be increased by using an extended end-to-end
      technique.

PMID- 19379985
TI  - The role of enucleation with or without septal myectomy for discrete subaortic
      stenosis.
AB  - OBJECTIVE: Substantial controversy persists regarding the need and efficacy of a
      routine myectomy in the treatment of discrete subaortic stenosis. Although some
      believe myectomy more effectively relieves subaortic narrowing, this is
      uncertain, and complications, including heart block and aortic valve injury, are
      concerns. The aims of the study were as follows: (1) to analyze the role of
      enucleation for relief of subaortic stenosis and the risk factors associated with
      recurrence and reoperation and (2) to delineate the characteristics of the
      patients who might benefit from enucleation alone. METHODS: From January 1990
      through May 2007, 221 patients with subaortic stenosis underwent biventricular
      repair. Of those, 106 patients had discrete subaortic stenosis. The preoperative
      peak left ventricular outflow tract gradient, as determined by means of
      transthoracic echocardiographic analysis, was 67.3 +/- 29 mm Hg. Forty patients
      had previous operations for other intracardiac anomalies. Mean age at repair was
      7 years. Sixty-one patients underwent isolated enucleation, and 45 patients
      underwent concomitant myectomy. Patients with recurrent subaortic stenosis whose
      first operation was performed elsewhere were excluded from analysis. RESULTS:
      There was 1 early death and 1 late death. The postoperative peak left ventricular
      outflow gradient decreased to 12.5 +/- 12.9 mm Hg (P < .001). No patient had
      development of heart block or required a pacemaker. A recurrent gradient of
      greater than 30 mm Hg was found in 26 (27%) patients, and 8 (7.5%) patients had
      reoperations. Actuarial freedom from reoperation rates at 5, 10, and 15 years
      were 94.7% +/- 1.8%, 89.6% +/- 3.5%, and 84.8% +/- 4.9%, respectively.Of those
      patients who had not undergone a previous cardiac operation, there were no
      significant differences in the rates of recurrence (28% vs 27%) or reoperation
      (4.7% vs 4.4%) between the enucleation group and the concomitant myectomy group.
      For the patients who had a previous cardiac operation, the concomitant myectomy
      group had a significantly lower rate of recurrence (44% for enucleation vs 13%
      for enucleation plus myectomy, P = .031). CONCLUSIONS: For those patients
      undergoing primary operations for discrete subaortic stenosis, routine myectomy
      does not offer superior relief of left ventricular outflow tract obstruction;
      enucleation alone provides good results in this selected population. However, in
      those patients with associated cardiac anomalies, concomitant additional myectomy
      is recommended.

PMID- 19379986
TI  - The analysis of a prospective surgical database improves postoperative fast
      tracking algorithms after pulmonary resection.
AB  - OBJECTIVE: We evaluated our results from our prospective database to identify
      possible modifications that may improve our fast-tracking protocols in selected
      high-risk patients. METHODS: We conducted a retrospective study of a prospective
      database. Using multivariable regression, we identified several patient
      characteristic that predicted failure to fast-track owing to increased morbidity.
      We modified our fast-tracking algorithm by substituting pain pumps for epidurals
      in elderly patients (>70 years). In addition, patients with a body mass index
      greater than 35 had increased aspiration precautions. Patients with poor
      pulmonary function (ratio of forced expiratory volume in 1 second to forced vital
      capacity and/or diffusing capacity/alveolar volume < 45%) underwent increased
      respiratory treatments and more aggressive ambulation. Differences in outcomes
      between groups were compared after adjusting for differing baseline patient
      characteristics, including use of a propensity score. RESULTS: A total of 2895
      patients underwent elective pulmonary resection before the algorithm
      modifications (January 1997-December 2001) and 3252 patients afterward (January
      2002-July 2007) by one surgeon. The length of stay was reduced by the protocol
      changes from 6.7 to 4.9 days (P = .024) in elderly patients, from 5.7 to 4.8 days
      in obese patients, and from 6.2 to 4.3 days (P = .008) in those with poor
      pulmonary function. Morbidity was reduced from 26% to 17% in elderly patients (P
      = .046), from 29% to 20% (P = .027) in obese patients, and from 45% to 23% in
      those with poor pulmonary function. Overall mortality was also reduced 4.0% to
      2.1% (P = .014). CONCLUSION: A prospective database provides important
      information that can lead to improvement in patient care by identifying specific
      complications. High-risk patients such as the elderly, the obese, and those with
      poor pulmonary function can safely undergo pulmonary resection and have a shorter
      hospital stay.

PMID- 19379988
TI  - Evaluation of the new TNM staging system proposed by the International
      Association for the Study of Lung Cancer at a single institution.
AB  - OBJECTIVE: The seventh TNM Classification of Malignant Tumours will be published
      in 2009. The International Association for the Study of Lung Cancer has proposed
      a revision of the current pathologic staging system. We illustrated the effects
      of this new system and pointed out potential problems using a retrospective study
      of surgical cases of non-small cell lung cancer at our institution. METHODS:
      Subjects were 1532 patients for whom current pathologic staging was possible.
      These data were migrated into the new staging system. The numbers of patients at
      various stages determined by using the current and new staging systems were,
      respectively, as follows: IA (n = 700, n = 700), IB (n = 338, n = 249), IIA (n =
      49, n = 164), IIB (n = 129, n = 116), IIIA (n = 204, n = 234), IIIB (n = 77, n =
      17), and IV (n = 35, n = 52). Prognoses were compared by using the current and
      the new systems. RESULTS: By using the new staging system, 5-year survivals by T
      classifications were as follows: T1a, 82.6%; T1b, 73.3%; T2a, 63.5%; T2b, 50.1%;
      T3, 40.6%; and T4, 34.6%. There were significant differences between the new T1a
      and T1b (P = .0026), T1b and T2a (P = .0027), and T2a and T2b (P = .0062)
      classifications. In the current system 5-year survivals based on pathologic
      stages were as follows: IA, 84.8%; IB, 72.9%; IIA, 53.8%; IIB, 53.7%; IIIA,
      31.8%; IIIB, 34.0%; and IV, 27.1%. There were significant differences between
      stages IA and IB (P < .0001) and stages IIB and IIIA (P = .0006). In the new
      system these were as follows: IA, 84.8%; IB, 75.2%; IIA, 62.4%; IIB, 52.1%; IIIA,
      32.4%; IIIB, 15.2%; and IV, 30.6%. There were significant differences between
      stages IA and IB (P = .0004), IB and IIA (P = .0195), IIA and IIB (P = .0257),
      IIB and IIIA (P = .0040), and IIIA and IIIB (P = .0399). CONCLUSION: Although the
      outcomes for stages IIIB and IV were reversed, the new pathologic staging system
      was considered valid based on our single-institution evaluation.

PMID- 19379989
TI  - Management of pleural recurrence after curative resection of thymoma.
AB  - OBJECTIVE: A complete surgical resection is the cornerstone of therapy of thymic
      tumors. Unfortunately, there is no standard treatment for pleural recurrence.
      This article describes our overall experience with the surgical treatment of
      pleural implants in patients who previously underwent resection of a thymoma.
      MATERIAL AND METHODS: From January 1980 to June 2006, 20 patients previously
      operated on for a thymoma were operated on for the surgical resection of pleural
      implants. Patients with the initial Masaoka stage IVA were excluded from our
      analysis. Our sample comprised 10 male and 10 female patients (12-65 years old).
      The surgical approach to the resection of the thymoma was as follows: video
      assissted thoracic surgery in 2 patients, sternotomy in 13 patients, thoracotomy
      in 2 patients, and sternothoracotomy in 3 patients. The initial Masaoka stage of
      the thymoma was IIA in 2 patients, IIB in 7 patients, and III in 11 patients.
      RESULTS: The interval between resection of the thymoma and pleural implants
      ranged from 11 to 156 (median 60) months. Fifteen patients had a thymus-related
      syndrome (in 13 patients it resulted myasthenia gravis), and in 11 patients it
      improved or remitted after treatment of the pleural recurrence. All the
      resections were performed through a posterolateral thoracotomy. Three patients
      underwent an iterative resection of new pleural implants. At the latest follow
      up, 10 patients are still alive (8 disease-free) and 10 have died (9 of a relapse
      and 1 of the complications of red cell aplasia). From the pleural recurrence
      resection, the overall 5- and 10-year survivals are 43.1% and 25.8%,
      respectively. CONCLUSIONS: Repeat operation on patients with thymoma pleural
      recurrences is feasible and safe. It can produce satisfactory results in terms of
      overall survival and paraneoplastic syndrome control. Moreover, the multimodality
      treatment could improve the results of surgical treatment.

PMID- 19379990
TI  - Stability of an autologous platelet clot in the pericardial sac: An experimental
      and clinical study.
AB  - OBJECTIVE: Autologous platelet clots serve as slow-release delivery systems for
      platelet-derived growth factors and cytokines. Their application to the
      pericardial sac might facilitate salvage and repair of ischemically injured
      myocardium. However, little is known about platelet clot stability in the
      pericardial sac. We investigated the stability of platelet clots in vitro and
      after administration to the pericardial sac in pigs and patients. METHODS: In 5
      Yorkshire-Landrace pigs and 10 patients, in vitro manufactured autologous
      platelet gel (Medtronic Magellan Platelet Separator) and platelet-rich fibrin
      (Vivolution Vivostat System) were administered to the pericardial sac for 30
      minutes. Two antifibrinolytics (tranexamic acid and aprotinin) were tested for
      their capacity to stabilize autologous platelet gel. In vitro clots, incubated at
      37 degrees C for 48 hours, served as controls. Clot weight was measured before
      and after administration. RESULTS: In vitro, autologous platelet gel clots of
      either formula liquefied almost entirely within 60 minutes whereas platelet-rich
      fibrin clots remained intact. In the pig, platelet clot weight decreased to 16.7%
      +/- 7.8% (P < .05) and 66.4% +/- 3.2% (P < .05) of initial clot weight for
      autologous platelet gel and platelet-rich fibrin, respectively. Addition of
      antifibrinolytics to autologous platelet gel did not reduce clot degradation
      significantly. In patients, autologous platelet gel and platelet-rich fibrin clot
      weight remained 9.0% +/- 1.5% (P < .05) and 73.7% +/- 2.6% (P < .05) of initial
      clot weight, respectively. CONCLUSIONS: Autologous platelet gel is unstable both
      in vitro and in vivo, whereas platelet-rich fibrin remains intact in vitro and,
      compared with autologous platelet gel, is less subject to degradation in pigs and
      in patients.

PMID- 19379991
TI  - Pediatric empyema: Outcome analysis of thoracoscopic management.
AB  - OBJECTIVE: Thoracoscopy has become a favored modality in treating pediatric
      empyema. However, the factors affecting the outcome of thoracoscopic management
      remain unclear. In this study, we report our experience using thoracoscopy to
      treat empyema in pediatric patients and investigate the factors affecting
      outcome. METHODS: We retrospectively reviewed the demographic data, clinical
      presentation, radiographic findings, laboratory studies, and hospital course of
      101 pediatric patients who underwent thoracoscopy for empyema between 1995 and
      2008. RESULTS: Empyema was due to pneumococcus infection in 64 patients (63.4%),
      and 69% of the cultured microorganisms were penicillin nonsusceptible. Chest
      computed tomography scan was performed in 96 patients, in whom necrotizing
      pneumonia was noted in 35 (36.5%). Preoperative intensive care unit admission was
      required for 33 patients (32.7%). Preoperative chest tube drainage was performed
      in 36 patients (35.6%), and thoracoscopy was used as the primary treatment in the
      remaining 65 patients. Complications occurred in 10 patients (9.9%); there were
      no mortalities. The median postoperative hospital stay was 13 days. Multivariate
      analyses showed that necrotizing pneumonia was significantly associated with the
      presence of complications, and that necrotizing pneumonia, preoperative intensive
      care unit admission, and preoperative chest tube drainage were independent risk
      factors for a longer postoperative hospital stay. CONCLUSION: The clinical
      presentations of empyema in children requiring thoracoscopy are diverse. Patients
      with necrotizing pneumonia and those requiring preoperative intensive care unit
      admission and undergoing preoperative chest tube drainage are at high risk for
      developing complications and requiring longer hospital stay after thoracoscopy.

PMID- 19379992
TI  - Quantification of the impact of segmentectomy on pulmonary function by perfusion
      single-photon-emission computed tomography and multidetector computed tomography.
AB  - OBJECTIVE: The impact of segmentectomy for preservation of pulmonary function was
      quantified by using a co-registered perfusion single-photon-emission computed
      tomography and multidetector computed tomography (SPECT/CT). METHODS: Pulmonary
      function tests and perfusion SPECT/CT were conducted before and after
      segmentectomy in 56 patients. Actual values of forced expiratory volume in 1
      second (FEV(1)) after segmentectomy were compared with the FEV(1) after virtual
      lobectomy, which was calculated by SPECT/CT. The preoperative and postoperative
      FEV(1) of each lobe that had undergone segmentectomy was measured by SPECT/CT.
      RESULTS: The mean percent of FEV(1) preserved after segmentectomy was
      significantly higher than the value after virtual lobectomy (88% +/- 9% vs 77% +/
      7%; P < .001). Whereas the mean value of the preoperative FEV(1) of each lobe
      that was undergoing segmentectomy was 0.51+/-0.21 L, segmentectomy could preserve
      41% +/- 24% of it. The FEV(1) of each lobe after the resection of more than three
      segments (n = 4) was preserved in 17% +/- 12% of the preoperative values, which
      was significantly less than 49% +/- 23% and 35% +/- 22% after the resection of
      one (n = 29) and two (n = 23) segments (P = .02 and .08, respectively). The
      FEV(1) of the left upper lobe after the upper division segmentectomy (n = 8) was
      preserved in 21% +/- 11% of the preoperative values, which was significantly less
      than 35% +/- 12% after the lingular segmentectomy (n = 7) (P = .03). CONCLUSION:
      Segmentectomy can preserve the pulmonary function more significantly than
      lobectomy, except for the resection of more than three segments or the left upper
      division segmentectomy.

PMID- 19379993
TI  - Myocardial revascularization with miniaturized extracorporeal circulation versus
      off pump: Evaluation of systemic and myocardial inflammatory response in a
      prospective randomized study.
AB  - OBJECTIVE: This prospective randomized study sought to verify the systemic
      inflammatory response, inflammatory myocardial damage, and early clinical outcome
      in coronary surgery with the miniaturized extracorporeal circulation system or on
      the beating heart. METHODS: Sixty consecutive patients were randomized to
      miniaturized extracorporeal circulation (n = 30) or off-pump coronary
      revascularization (off-pump coronary artery bypass grafting, n = 30).
      Intraoperative and postoperative data were recorded. Plasma levels of interleukin
      6 and tumor necrosis factor-alpha were measured from systemic blood
      intraoperatively, at the end of operation, and 24 and 48 hours thereafter. Levels
      of the same markers and blood lactate were measured from coronary sinus blood
      intraoperatively to evaluate myocardial inflammation. Markers of myocardial
      damage were also analyzed. RESULTS: One patient died in the off-pump coronary
      artery bypass grafting group. There was no statistical difference in early
      clinical outcome in both groups. Release of interleukin-6 was higher in the off
      pump coronary artery bypass grafting group 24 hours after the operation (P =
      .03), whereas levels of tumor necrosis factor-alpha were not different in both
      groups. Cardiac release of interleukin-6, tumor necrosis factor-alpha, and blood
      lactate were not different in both groups. Release of troponin T was not
      significantly different in both groups. Levels of creatine kinase mass were
      statistically higher in the miniaturized extracorporeal circulation group than in
      the off-pump coronary artery bypass grafting group, but only at the end of the
      operation (P < .0001). Hemoglobin levels were significantly higher in the
      miniaturized extracorporeal circulation group than in the off-pump coronary
      artery bypass grafting group after 24 hours (P = .01). CONCLUSION: Miniaturized
      extracorporeal circulation can be considered similar to off-pump surgery in terms
      of systemic inflammatory response, myocardial inflammation and damage, and early
      outcome.

PMID- 19379994
TI  - Dynamic computed tomography to determine cardiac output in patients with left
      ventricular assist devices.
AB  - OBJECTIVE: The purpose of this study was to develop and test a novel, noninvasive
      means of estimating cardiac output in patients with continuous-flow left
      ventricular assist devices. METHODS: Based on the indicator dilution principle,
      we estimated cardiac output from signal intensity versus time recordings during
      first-pass imaging with contrast-enhanced computed tomography. To account for
      recirculation, a gamma variate function was modified to model the indicator
      concentration curve. A proportionality constant for 64-slice computed tomography
      data acquisition was derived relating computed tomography Hounsfield units to
      indicator concentration. Validity of the equation was tested in ambulatory
      patients with continuous-flow left ventricular assist devices who underwent
      simultaneous computed tomography and Swan-Ganz catheter thermodilution-based
      measurement of cardiac output at various left ventricular assist device rpm
      settings. Agreement between measurements was testing using kappa statistic.
      RESULTS: Pairwise comparison of calculated output using the dynamic computed
      tomography test bolus technique versus thermodilution output measurements yielded
      good agreement (P = .03). The output calculated using dynamic computed tomography
      underestimated the thermodilution output measurement by 0.54 +/- 0.37 L/min (95%
      confidence interval, 0.66-0.94). CONCLUSIONS: Noninvasive estimation of cardiac
      output from left ventricular assist devices is feasible using first-pass dynamic
      computed tomography. By affording simultaneous good visualization of the device
      in situ, computed tomography may be useful for noninvasive assessment of location
      and function of ambulatory patients with left ventricular assist devices.

PMID- 19379995
TI  - A differential release of matrix metalloproteinases 9 and 2 during coronary
      artery bypass grafting and off-pump coronary artery bypass surgery.
AB  - OBJECTIVES: Extracorporeal circulation is associated with the systemic
      inflammatory response syndrome. The objective of this study was to measure plasma
      and myocardial matrix metalloproteinase 2 and 9 levels in patients undergoing off
      pump coronary artery bypass and coronary artery bypass grafting. METHODS: Twenty
      patients subjected to coronary artery bypass grafting and 20 subjected to off
      pump coronary artery bypass surgery were included in this study. In both
      procedures blood was collected in 7 equivalent time points up to 12 hours after
      grafting. The myocardial biopsy specimens were collected before and after
      extracorporeal circulation in the coronary artery bypass grafting group and after
      harvesting and completion of proximal anastomoses in the off-pump coronary artery
      bypass group. Matrix metalloproteinase levels were measured by means of
      zymography. Myeloperoxidase and tissue inhibitor of metalloproteinase 1 and 2
      levels were measured with an enzyme-linked immunosorbent assay. RESULTS: Coronary
      artery bypass grafting but not off-pump coronary artery bypass led to a 700- to
      900-fold increase of plasma matrix metalloproteinase 9 levels. A small but
      significant increase in matrix metalloproteinase 2 levels was detected in both
      procedures. Myocardial matrix metalloproteinase 9 levels significantly increased
      at the end of coronary artery bypass grafting and off-pump coronary artery
      bypass. Increased matrix metalloproteinase 9 activity at the end of
      extracorporeal circulation was accompanied by augmentation of the endogenous
      matrix metalloproteinase inhibitors tissue inhibitor of metalloproteinase 1 and 2
      in plasma, but its magnitude was unable to balance the plasma matrix
      metalloproteinase 9 increase. The matrix metalloproteinase 9 content in plasma at
      the end of extracorporeal circulation correlated with the myeloperoxidase plasma
      concentration (r(2) = 0.8212, P < 0.05). CONCLUSION: We propose that release of
      matrix metalloproteinase 9 might contribute to the extracorporeal circulation
      induced inflammatory reactions.

PMID- 19379996
TI  - Tracking cardiac engraftment and distribution of implanted bone marrow cells:
      Comparing intra-aortic, intravenous, and intramyocardial delivery.
AB  - OBJECTIVES: Cell therapy improved cardiac function after a myocardial infarction
      in several preclinical studies; however, the functional benefits were limited in
      the initial clinical trials, perhaps because of inadequate cell engraftment. We
      used noninvasive molecular imaging to compare the distribution and myocardial
      retention of cells implanted by using clinical delivery routes. METHODS: Bone
      marrow stromal cells isolated from male rats and transfected with a firefly
      luciferase reporter gene were injected by using 3 increasingly invasive
      techniques (ie, intravenous, intra-aortic, and intramyocardial) into female rats
      3 or 28 days after coronary ligation. Whole-body bioluminescence imaging was
      performed 2, 24, and 48 hours later; implanted cells were quantified at 48 hours
      in explanted organs by means of bioluminescence and real-time polymerase chain
      reaction. RESULTS: Variations in cell distribution among groups were profound,
      with nearly complete trapping of the injected cells in the lungs after
      intravenous delivery. Cell delivery into the aortic root (with the distal aorta
      occluded) produced minimal cell retention in the heart. Direct intramyocardial
      injection facilitated the best early targeting of the cells (P < .05 vs
      intravenous and intra-aortic injection). Rapid signal loss over 48 hours
      indicated very poor cell survival in all 3 groups, although implanted cell
      retention was greater in mature compared with acute infarcts. CONCLUSIONS: This
      is the first study to correlate live cell imaging with quantitative genetic and
      histologic techniques. Noninvasive molecular imaging tracked delivered cells and
      will permit the evaluation of new and improved delivery platforms designed to
      increase cell homing, retention, and engraftment.

PMID- 19379997
TI  - Matching donor to recipient in lung transplantation: How much does size matter?
AB  - OBJECTIVE: The impact of size matching between donor and recipient is unclear in
      lung transplantation. Therefore, we determined the relation of donor lung size to
      1) posttransplant survival and 2) pulmonary function as measured by forced
      expiratory volume in 1 second. METHODS: From 1990 to 2006, 469 adults underwent
      lung transplantation with lungs from donors aged 7 to 70 years. Donor and
      recipient total lung capacities were calculated using established formulae
      (predicted total lung capacity), and actual recipient lung size was measured in
      the pulmonary function laboratory. Disparity between donor and recipient lung
      size was expressed as a ratio of donor predicted total lung capacity to recipient
      predicted total lung capacity-the predicted total lung capacity ratio-and
      predicted donor total lung capacity to actual recipient total lung capacity-the
      actual total lung capacity ratio. Survival was measured by multiphase hazard
      methodology and repeated measures of National Health and Nutrition Examination
      Survey-normalized forced expiratory volume in 1 second analyzed by temporal
      decomposition. RESULTS: Predicted total lung capacity ratio and actual total lung
      capacity ratio ranged widely, from 0.55 to 1.59 and 0.52 to 4.20, respectively.
      Overall survival was unaffected by predicted total lung capacity ratio (P = .3)
      or actual total lung capacity ratio (P = .5). Patients with emphysema and an
      actual total lung capacity ratio of 0.67 or less or 1.03 or greater had higher
      predicted mortality (P = .01). During the first posttransplant year, forced
      expiratory volume in 1 second increased and then gradually declined. Predicted
      total lung capacity ratio and actual total lung capacity ratio had a small impact
      on forced expiratory volume in 1 second, primarily in the late phase after
      transplant in a disease-specific manner. CONCLUSION: Size matching between donor
      and recipient using predicted total lung capacity ratio and actual total lung
      capacity ratio is an effective technique. Wide discrepancies in lung sizing do
      not affect overall posttransplant survival or pulmonary function. Therefore, a
      greater degree of lung size mismatch can likely be accepted, thereby improving
      patients' odds of undergoing transplantation.

PMID- 19379998
TI  - Enhanced fibrinolysis protects against lung ischemia-reperfusion injury.
AB  - OBJECTIVE: Ischemia-reperfusion injury continues to plague the field of lung
      transplantation, resulting in suboptimal outcomes. In acute lung injury,
      processes such as ventilator-induced injury, sepsis, or acute respiratory
      distress syndrome, extravascular fibrin has been shown to promote lung
      dysfunction and the acute inflammatory response. This study investigates the role
      of the fibrinolytic cascade in lung ischemia-reperfusion injury and investigates
      the interplay between the fibrinolytic system and the inflammatory response.
      METHODS: Mice lacking the plasminogen activator inhibitor-1 gene (PAI-1 knock
      out, PAI-1 KO; and thus increased lysis of endogenous fibrin) and wild-type mice
      underwent in situ left lung ischemia and reperfusion. Fibrin content in the lung
      was evaluated by immunoblotting. Reperfusion injury was assessed by histologic
      and physiologic parameters. Proinflammatory mediators were measured in
      bronchoalveolar lavage fluid and plasma using enzyme-linked immunosorbent assays.
      RESULTS: Ischemia-reperfusion causes fibrin deposition in murine lungs. Less
      fibrin was seen in PAI-1 KO mice than in wild-type mice subjected to the same
      ischemia-reperfusion conditions. By histologic criteria, more evidence of
      ischemia-reperfusion injury was noted (thickening of the interstium, cellular
      infiltration in the alveoli) in the wild-type than in PAI-1 KO mice. Physiologic
      parameters also revealed more ischemia-reperfusion injury in the wild-type than
      in PAI-1 KO mice. Cytokine and chemokines were elevated more in the wild-type
      group than the PAI-1 KO group. CONCLUSIONS: Lung ischemia-reperfusion injury
      triggers fibrin deposition in the murine lungs and fibrin creates a
      proinflammatory environment. Preventing fibrin deposition may reduce ischemia
      reperfusion injury and inflammation. This finding may lead to novel treatment
      strategies for ischemia-reperfusion.

PMID- 19379999
TI  - Long-acting oral phosphodiesterase inhibition preconditions against reperfusion
      injury in an experimental lung transplantation model.
AB  - OBJECTIVES: Ischemia-reperfusion injury remains a devastating complication of
      lung transplantation. Phosphodiesterase inhibitors have been shown to
      precondition tissues against ischemia-reperfusion injury. Little is known,
      however, about the utility of phosphodiesterase inhibition in reperfusion injury
      after lung transplantation. We evaluated the long-acting phosphodiesterase-5
      inhibitor, tadalafil, in an ex vivo lung transplant model. METHODS: New Zealand
      White rabbits (4 kg), were given oral tadalafil (n = 11) 24 hours before lung
      harvest and compared with rabbits given oral vehicle alone (n = 11). Lungs were
      recovered with Perfadex solution (Vitrolife, Kungsbacka, Sweden) and cold stored
      for 18 hours. After storage, lung blocks were reperfused with donor rabbit blood
      in an ex vivo apparatus. Pulmonary artery pressures were recorded with serial
      arterial and venous blood gas sampling and animals served as their own controls.
      Phosphodiesterase-5 and protein kinase G tissue activity assays confirmed drug
      effects. Luminol chemiluminescence assay was used to measure reactive oxygen
      species and levels of endothelial and inducible nitric oxide synthase were
      measured. RESULTS: Extended cold storage, followed by reperfusion produced a
      consistent reproducible decrease in oxygenation and increase in pulmonary
      pressure. Tadalafil-treated animals exhibited greater Pao(2) throughout the
      course of reperfusion (P = .001) Mean pulmonary artery pressure was lower in
      tadalafil-treated animals (22 vs 40 mm Hg; P = .04). Phosphodiesterase-5 activity
      was decreased (143 +/- 8 vs 205 +/- 32 mP; P < .001) with protein kinase G
      activity increased (25 +/- 12 vs 12 +/- 2.4 fU/microg; P = .01) in the
      experimental group confirming that oral pretreatment resulted in active
      phosphodiesterase inhibition in the lung tissue. Reactive oxygen species (as
      measured by luminol activity) were decreased in tadalafil-treated animals (7.8 +/
      1.5 vs 10.2 +/- 1.2 relative light units; P = .003). CONCLUSIONS: Our
      experimental model demonstrates that oral donor pretreatment with a long-acting
      phosphodiesterase inhibitor is an effective strategy for improving pulmonary
      performance after reperfusion. Importantly, phosphodiesterase enzymes and their
      downstream effectors may play a critical role in reperfusion injury after lung
      transplantation.

PMID- 19380001
TI  - Prevalence of significant peripheral artery disease in patients evaluated for
      percutaneous aortic valve insertion: Preprocedural assessment with multidetector
      computed tomography.
AB  - OBJECTIVES: Percutaneous aortic valve insertion is an emerging treatment option
      for selected patients with severe aortic stenosis and may be done from a
      transfemoral or transapical approach. Concomitant atherosclerotic peripheral
      artery disease limits transfemoral access. We evaluated the potential role of
      multidetector computed tomography in preoperative assessment of vascular anatomy.
      METHODS: Consecutive patients with severe aortic stenosis were included. Contrast
      enhanced computed tomographic angiography of the thoracic and abdominal aorta and
      iliofemoral arteries was performed. Criteria of unfavorable iliofemoral anatomy
      were defined as a minimal luminal diameter of the common iliac, external iliac,
      or common femoral arteries of less than 8 mm, presence of greater than 60%
      circumferential calcification at the external-internal iliac bifurcation, and
      severe angulation between the common and external iliac arteries (< 90 degrees ).
      The prevalence of these criteria was evaluated and infrarenal aortic and
      iliofemoral arterial anatomy was compared in the groups with and without
      peripheral artery disease for any of these criteria. RESULTS: One hundred
      patients (79 +/- 9 years, 59% male) were included. A total of 35 (35%) patients
      had at least one criterion of unsuitable iliofemoral anatomy, including 27
      patients with small minimal luminal diameter (<8 mm), 12 patients with severe
      circumferential calcification at the iliac bifurcation (>60%), and 4 with severe
      angulation of the iliac arteries (<90 degrees ). CONCLUSIONS: Significant
      atherosclerotic peripheral artery disease is common in the high-risk patient
      population currently evaluated for percutaneous aortic valve insertion. Computed
      tomography allows identification of patients with iliofemoral anatomy unfavorable
      for the transfemoral approach to percutaneous aortic valve insertion.

PMID- 19380002
TI  - Epicardial off-pump pulmonary vein isolation and vagal denervation improve long
      term outcome and quality of life in patients with atrial fibrillation.
AB  - OBJECTIVES: The limited information available on thoracoscopic pulmonary vein
      isolation combined with ganglionated plexi ablation and the lack of studies
      regarding its effect on quality of life and physical capacity urged us to study
      its acute and long-term results in patients with atrial fibrillation. METHODS:
      Forty-three patients (mean age 57.1 years) with symptomatic atrial fibrillation
      referred for thoracoscopic off-pump epicardial pulmonary vein isolation and
      ganglionated plexi ablation using radiofrequency energy were included. RESULTS:
      The physical capacity improved significantly at 6-month follow-up compared with
      baseline (mean +/- standard deviation, 165.2 +/- 65 Watt versus 155.9 +/- 57
      Watt, P = .02). Quality of life (Short Form-36 health survey) significantly
      improved 12 months after surgery compared with baseline in all subscales except
      for bodily pain. The symptom severity questionnaire score decreased significantly
      from mean 15.2 +/- 4.0 points to 10.7 +/- 4.8 points (P = .02). Overall, 25 of 33
      patients (76%) followed up for 12 months had no symptomatic atrial fibrillation
      recurrences or atrial fibrillation episodes on 24-hour Holter recordings. The
      corresponding figures were 79% (19/24) for patients with paroxysmal atrial
      fibrillation, 100% (2/2) for persistent atrial fibrillation, and 57% (4/7) for
      permanent atrial fibrillation. The most common complication was bleeding events
      (9%) during pulmonary vein dissection. CONCLUSIONS: Epicardial off-pump pulmonary
      vein isolation combined with ganglionated plexi ablation improved quality of
      life, symptoms, and exercise capacity and therefore may be considered for
      patients with atrial fibrillation who fail endocardial pulmonary vein ablation or
      as a first-line procedure if left atrial appendage exclusion is warranted.

PMID- 19380003
TI  - Cavernous hemangioma of the bronchial wall: A systemic-pulmonary vessel fistula.

PMID- 19380004
TI  - Early calcification of a stentless pericardial bioprosthesis in the elderly.

PMID- 19380005
TI  - Acute rupture of both papillary muscles after aortic valve replacement for
      infective endocarditis.

PMID- 19380006
TI  - Spontaneous regression of a mediastinal thymoma.

PMID- 19380007
TI  - Acute myocardial infarction and limb ischemia as manifestation of nonbacterial
      thrombotic endocarditis.

PMID- 19380008
TI  - Multiple papillary fibroelastoma with quadricuspid aortic valve.

PMID- 19380009
TI  - Pulmonary venous obstruction in a patient with Marfan syndrome: Rare presentation
      of an expanding dissecting descending thoracic aortic aneurysm with annuloaortic
      ectasia.

PMID- 19380010
TI  - Ascending aortic pseudoaneurysm after aortic valve replacement: Watch the tip of
      the cardioplegia cannula!

PMID- 19380011
TI  - Dual left ventricular restorations in a patient with cardiac sarcoidosis.

PMID- 19380012
TI  - Potential role of the Impella Recover left ventricular assist device in the
      management of postinfarct ventricular septal defect.

PMID- 19380013
TI  - Aortic dissection type A after supra-aortic debranching and implantation of an
      endovascular stent-graft for type B dissection: A word of caution.

PMID- 19380014
TI  - Why are the results reported from this center inconsistant with the general
      experience of 4000 implants and 10 years of follow-up?

PMID- 19380016
TI  - Shelhigh bioprosthesis in active infective endocarditis.

PMID- 19380018
TI  - Distal axillary artery cannulation can be useful to achieve arterial inflow in
      descending aortic surgery.

PMID- 19380021
TI  - Genetic alterations detected by comparative genomic hybridization and recurrence
      rate in epithelial ovarian carcinoma.
AB  - To assess the putative correlation between comparative genomic hybridization
      (CGH)-detectable genetic alterations in epithelial ovarian cancer and disease
      recurrence, conventional CGH was performed on 45 epithelial ovarian cancers: 26
      tumors from sporadic, BRCA mutation noncarriers and 11 and 8 tumors from BRCA1
      and BRCA2 mutation carriers, respectively. Relevant clinical data, including
      histology, grade, stage, size of residual tumor, recurrence, and survival, were
      obtained from outpatient and inpatient charts. Among the 45 cases, the most
      common regions involving gain of DNA copy number were 3q (n = 23; 51%), 8q (n =
      21; 47%), and 1q (n = 14; 31%), and the most common regions with loss were 19 and
      22 at 9 cases (20%) each, followed by 5q (n = 6; 13%). In multivariate analysis,
      the total number of genetic alterations was not associated with risk of
      recurrence, but gain in 5p was associated with a higher risk of recurrence
      (hazard ratio HR = 6.06, P = 0.0399), and gain in 1p as well as loss in 5q were
      associated with a significant decrease in recurrence (HR = 0.08, P = 0.0079, and
      HR = 0.10, P = 0.0143, respectively). Recurrence rate in patients with epithelial
      ovarian cancer is seemingly associated with specific genetic alterations detected
      by CGH, but the specific genes involved and the implications of these findings
      await further studies.

PMID- 19380020
TI  - Preoperative chemoradiotherapy in locally advanced rectal cancer: correlation of
      a gene expression-based response signature with recurrence.
AB  - Preoperative chemoradiotherapy is recommended for locally advanced rectal cancer
      (UICC stage II/III). We recently demonstrated that responsive and nonresponsive
      tumors showed differential expression levels of 54 genes. In this follow-up
      study, we investigated the relationship between this gene set and disease-free
      (DFS) and overall survival (OS). Pretherapeutic biopsies from 30 participants in
      the CAO/ARO/AIO-94 trial of the German Rectal Cancer Study Group were analyzed
      using gene expression microarrays. Statistical analysis was performed to identify
      differentially expressed genes between recurrent and nonrecurrent tumors and to
      correlate these changes with disease recurrence and outcome. After a median
      follow-up of 59 months, seven of eight patients with recurrent disease was a
      nonresponder, and one responsive tumor recurred. Response to chemoradiotherapy
      was significantly correlated with an improved DFS (log rank P=0.028), whereas OS
      did not differ significantly (P=0.11). Applying a class comparison analysis, we
      identified 20 genes that were differentially expressed between recurrent and
      nonrecurrent tumors (P<0.001). Analyzing the first two principal components of
      the 54 genes previously identified to predict response, we observed that this
      response signature correlated with an increased risk of cancer recurrence. These
      data suggest that the genetic basis of local response also affects the genetic
      basis of tumor recurrence. Genes that are indicative of nonresponse to
      preoperative chemoradiotherapy might also be linked to an increased risk of tumor
      recurrence.

PMID- 19380022
TI  - A functional promoter polymorphism in the TERT gene does not affect inherited
      susceptibility to breast cancer.
AB  - Telomere dysfunction is a key mechanism in cancer development. The human
      telomerase reverse transcriptase (TERT) is the rate-limiting catalytic subunit of
      the telomerase enzyme, which is necessary for the maintenance of telomere DNA
      length, chromosomal stability, and cellular immortality. In our attempt to
      identify functional polymorphisms in the TERT gene and their effect on breast
      cancer risk, we sequenced the promoter of the gene and identified three single
      nucleotide polymorphisms (SNPs) with a frequency of at least 10%. One of these
      SNPs, rs2853669 (-244 T > C), has been shown to affect telomerase activity and
      telomere length. Recently, this SNP has been suggested to affect familial breast
      cancer risk. In our case-control study using two large breast cancer sample
      series, including one with 841 cases with inherited susceptibility to breast
      cancer, we did not find any association with familial or sporadic breast cancer
      risk. This well-powered study excludes an effect of the functional -244 T > C SNP
      and two other correlated SNPs on breast cancer risk.

PMID- 19380023
TI  - Molecular analyses of cell origin and detection of circulating tumor cells in the
      peripheral blood in alveolar soft part sarcoma.
AB  - Alveolar soft part sarcoma (ASPS) is a distinct, rare soft tissue tumor with an
      unknown histogenesis and a tendency for late widespread metastases to lung, bone,
      and brain. It is now clear that they are caused by a specific unbalanced
      translocation, der(17)t(X;17)(p11;q25), which results in the formation of an
      ASPSCR1-TFE3 (alias ASPL-TFE3) fusion gene. The rearrangement results in the
      expression of chimeric transcripts, which can be identified by means of reverse
      transcriptase-polymerase chain reaction (RT-PCR). We investigated the
      histogenesis of ASPS and attempted to detect circulating ASPS tumor cells in
      peripheral blood. The immunohistochemical and genetic details of four cases and
      one cell line of ASPS were examined. An immunohistochemical analysis and RT-PCR
      did not detect myogenic differentiation gene MYOD1. The sensitivity of nested RT
      PCR for detection of circulating ASPS cells was assessed by demonstrating that
      the tumor cell-associated gene translocation could be detected in 50 tumor
      cells/2 mL of blood. Clinically, it was detectable in a peripheral blood sample
      (2 mL) of ASPS patient with distant metastases. The findings suggest that ASPS is
      not of skeletal muscle origin. ASPS tumor cells in the peripheral blood could be
      monitored by RT-PCR.

PMID- 19380024
TI  - Adrenaline induces chemoresistance in HT-29 colon adenocarcinoma cells.
AB  - Psychological distress and its ensuing chronic elevation of plasma catecholamines
      (adrenaline and noradrenaline) lead to poor response of tumors to chemotherapy,
      and constitute a poor prognostic factor for survival. Colorectal cancer patients
      suffer from various forms of psychological stress reflected in elevated plasma
      catecholamines, and their cancer cells express adrenergic receptors. Our
      objective was to investigate whether adrenergic activation contributes to the
      chemoresistance of colon cancers, and to explore the signal transduction pathway
      involved in the activation. The mRNA expression of the ABCB1 gene (previously
      MDR1) in human colon carcinoma HT-29 cell line was measured after treatment with
      an adrenergic receptor agonist (adrenaline) and various antagonists (propranolol,
      prazosin, and yohimbine). The function of P-glycoprotein, the protein product of
      the ABCB1 gene, was assessed by rhodamine 123 (Rh123)-retention assay, and
      chemosensitivity was determined by evaluating the cytotoxicity of 5-fluorouracil
      (5-FU) on the tumor cells. Increased ABCB1 mRNA expression and P-glycoprotein
      function levels in HT-29 cells by adrenaline was dose-dependent. This was
      accompanied by promotion of Rh123 efflux, and resistance to the growth-inhibiting
      effect of 5-FU in the tumor cells. The alpha2-adrenergic receptor antagonist
      yohimbine completely abolished the induction of ABCB1 mRNA, the stimulatory
      effect of adrenaline on Rh123 efflux, and the growth-inhibiting effect of 5-FU.
      The alpha1-adrenergic receptor and beta-adrenergic receptor antagonists did not
      inhibit the induction of ABCB1. The stimulating effects were coupled with
      extracellular receptor kinase 1/2 (Erk1/2) phosphorylation, but were not
      associated with protein kinase A activity. We conclude that adrenaline induces
      multidrug resistance in colon cancer cells by upregulating ABCB1 gene expression
      via alpha2-adrenergic receptors, and such effects were associated with the
      mitogen activated protein kinase (MAPK) pathway.

PMID- 19380025
TI  - The association between Toll-like receptor 4 (TLR4) polymorphisms and the risk of
      prostate cancer in Korean men.
AB  - The Toll-like receptor 4 (TLR4) has a wide spectrum of bacteria recognition
      receptors that may be involved in the signaling of the immune responses in the
      prostate. A few association studies have assessed the relationship between the
      risk of prostate cancer (PC) and the polymorphism in the TLR4 gene in European
      ancestry populations. To evaluate the association of TLR4 polymorphisms and the
      risk for PC in Korean men, we genotyped five single-nucleotide polymorphisms
      (SNPs) of the TRL4 gene (rs11536858, rs1927914, 1927911, rs11536891, and
      rs11536897) by PCR-restriction fragment length polymorphism from unrelated 157 PC
      patients and 143 age-matched controls. The rs1927911 SNP increased the risk of PC
      (adjusted odds ratio ORadj=2.73, 95% CI=1.54-4.87 for the TC genotype;
      ORadj=6.68, 95% CI=3.27-13.66 for the CC genotype). The GG genotype of the
      rs11536858 SNP also carried increased risk (ORadj=2.296, 95% CI=1.07-4.93). There
      was no statistically significant correlation between any of the SNPs of TRL4 and
      such PC prognostic factors as Gleason grade, initial prostate-specific antigen
      level, or tumor stage. In conclusion, inherited differences in the TLR4 gene
      influence the risk of PC in Korean men.

PMID- 19380026
TI  - Allelic status of 1p and 19q in oligodendrogliomas and glioblastomas: multiplex
      ligation-dependent probe amplification versus loss of heterozygosity.
AB  - Identification of the 1p/19q allelic status in gliomas, primarily those with a
      major oligodendroglial component, has become an excellent molecular complement to
      tumor histology in order to identify those cases sensitive to chemotherapy. In
      addition to loss of heterozygosity (LOH), fluorescence in situ hybridization
      (FISH), or comparative genomic hybridization (CGH), multiplex ligation-dependent
      probe amplification (MLPA) has been shown to be an alternative methodology to
      identify deletions of those chromosome arms. We used MLPA to explore the 1p and
      19q allelic constitution in a series of 76 gliomas: 41 tumors with a major
      oligodendroglial component, 34 glioblastomas, and one low-grade astrocytoma. We
      compared the MLPA findings of the oligodendroglial cases with those previously
      obtained using LOH in the same samples. Thirty-eight of 41 oligodendrogliomas
      displayed identical findings by both LOH and MLPA, and losses at either 1p and/or
      19q were identified in 12 of 35 (34%) astrocytic tumors. These findings agree
      with data previously reported comparing MLPA versus FISH or CGH in gliomas and
      suggest that MLPA can be used in the identification of the 1p/19q allelic
      deletions on these brain neoplasms.

PMID- 19380027
TI  - Acute myeloid leukemia and diabetes insipidus with monosomy 7.
AB  - The predisposition of monosomy 7 to diabetes insipidus (DI) in acute myeloid
      leukemia (AML) led us to ask whether AML associated with monosomy 7 and DI will
      differ from AML associated with other karyotype aberrations and DI and whether
      the outcome of patients with AML and DI will differ from those without DI. We
      describe 2 patients from Roswell Park Cancer Institute and discuss 29 additional
      cases from the literature. AML with monosomy 7 and DI (n = 25) had a trend
      towards a lower complete remission (p = 0.0936) and worse survival (p = 0.0480)
      than AML with other karyotype changes and DI (n = 6). Further, AML with monosomy
      7 and DI had worse complete remission rate and overall survival than AML with
      monosomy 7 but without DI. In conclusion, it appears that AML with monosomy 7 and
      DI is a disease entity with specifically poor outcome.

PMID- 19380028
TI  - Combined effect of smoking and inherited polymorphisms in arylamine N
      acetyltransferase 2, glutathione S-transferases M1 and T1 on bladder cancer in a
      Tunisian population.
AB  - Cigarette smoking is the predominant risk factor for bladder cancer in males and
      females. The tobacco carcinogens are metabolized by various xenobiotic
      metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT)
      and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter
      the ability of these enzymes to metabolize carcinogens. We have conducted this
      case-control study to assess the role of smoking, slow NAT2 variants, and GSTM1
      and GSTT1 null genotypes in bladder cancer development in North Tunisia. In all
      groups of patients, we have shown that GSTM1 and GSTT1 null genotypes did not
      appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow
      acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased
      risk of bladder (OR=7.14; 95% CI: 1.30-51.41). Furthermore, we found that NAT2
      slow acetylator individuals temporarily carrying wild-type GSTT1 or GSTM1 null
      genotypes have a strong increased risk of bladder cancer (OR= 26 and 22.17,
      respectively). This cumulative effect was estimated at 12 for smokers harboring
      slow or an intermediate NAT2, GSTM1 null, and wild-type GSTT1 genotypes compared
      to non-smokers carrying rapid NAT2, wild-type GSTM,1 and GSTT1 null genotypes
      (p=0.02; OR=12; CI 95% 1-323.76).

PMID- 19380029
TI  - NUP98-NSD3 fusion gene in radiation-associated myelodysplastic syndrome with
      t(8;11)(p11;p15) and expression pattern of NSD family genes.
AB  - Chromosomal 11p15 abnormality of therapy-related myelodysplastic syndrome (t-MDS)
      acute myeloid leukemia (AML) is rare. NUP98-NSD3 fusion transcripts have been
      detected previously in one patient with AML and one patient with t-MDS having
      t(8;11)(p11;p15). Here we present the case of a 60-year-old man with radiation
      associated MDS (r-MDS) carrying chromosome abnormalities, including
      t(8;11)(p11;p15) and del(1)(p22p32). Fluorescence in situ hybridization analysis
      demonstrated that the NUP98 gene at 11p15 was split by the translocation.
      Southern blot analysis of bone marrow cells showed both rearrangements of NUP98
      and NSD3 genes. Reverse transcriptase-polymerase chain reaction (RT-PCR) followed
      by sequence analysis revealed the presence of both NUP98-NSD3 and NSD3-NUP98
      fusion transcripts. Expression analysis by RT-PCR showed that NSD3 as well as
      NSD1 and NSD2 was ubiquitously expressed in leukemic cell lines and Epstein-Barr
      virus transformed B lymphocyte cell lines derived from the normal adult
      lymphocytes examined. Two isoforms of NSD3, NSD3S and NSD3L (but not NSD3L2),
      were expressed in leukemic cell lines and were fused to NUP98 in our patient,
      suggesting that qualitative change of these two isoforms of NSD3 by fusion with
      NUP98 might be related to leukemogenesis, although the function of each isoform
      of the NSD3 gene remains unclear.

PMID- 19380030
TI  - Cryptic insertion into 11q23 of MLLT10 not involved in
      t(1;15;11;10)(p36;q11;q23;q24) in infant acute biphenotypic leukemia.
AB  - The MLL gene, located on chromosomal band 11q23, is fused to a large number of
      different partner genes in hematological malignancies. This report describes a
      case of infant acute biphenotypic leukemia with t(1;15;11;10)(p36;q11;q23;q24).
      Panhandle polymerase chain reaction (PCR) using cDNA demonstrated the formation
      of an MLL-MLLT10 fusion transcript, although the 10p12 segment, at which the
      MLLT10 gene is located, was not involved in the breakpoint of the four-way
      translocation according to G-banding and spectral karyotyping analyses. Long
      distance inverse PCR using genomic DNA revealed that intron 7 of MLL was fused
      with intron 8 of MLLT10, which was connected with a DNA segment of noncoding
      region on 15q. In fluorescence in situ hybridization analyses, the duplicated 3'
      part of MLLT10 was inserted into the component of chromosome 15 on der(11)(q23).
      In real-time quantitative PCR with primers that recognized the DNA sequence of
      the two sites of fusion point, the minimal residual disease (MRD) levels changed
      in parallel with other clinical markers. Furthermore, the level of MRD had
      already increased before hematologic relapse. The identification and
      characterization of MLL rearrangement at the genomic DNA level may be useful for
      MRD quantification.

PMID- 19380031
TI  - Hyperdiploidy with trisomy 9 and deletion of the CDKN2A locus in T-cell acute
      lymphoblastic leukemia.
AB  - We describe the rare finding of a T-cell acute lymphoblastic leukemia (T-ALL) and
      a pretreatment bone marrow karyotype mosaic for four distinct cell lines in a 4
      year-old boy. G-banding analysis of metaphase cells identified a hyperdiploid
      cell line (52 chromosomes) trisomic for chromosomes 6, 9, 11, 13, 19, and 22.
      Fluorescence in situ hybridization (FISH) analysis demonstrated that these
      hyperdiploid cells were missing all three copies of the CDKN2A locus (alias
      p16/Ink4) at 9p21. FISH analysis of interphase nuclei identified two abnormal
      cell lines: the majority of cells with homozygous deletions of the CDKN2A locus
      and some with a heterozygous deletion. In addition, a normal signal pattern was
      identified in a few cells. This case represents a rare case of hyperdiploidy in T
      ALL, and characterizes the clonal evolution of the 9p21 deletion leading to the
      abnormal karyotype.

PMID- 19380034
TI  - Images in emergency medicine. Knotting of a urinary catheter.

PMID- 19380032
TI  - Long-term persistence of nonpathogenic clonal chromosome abnormalities in donor
      hematopoietic cells after allogeneic stem cell transplantation.
AB  - We describe the cases of two unrelated patients who exhibited multiple
      chromosomal abnormalities in donor cells after allogeneic peripheral blood stem
      cell transplantation (PBSCT). The patients were diagnosed with chronic myeloid
      leukemia and chronic lymphocytic leukemia, respectively, and both underwent
      nonmyeloablative conditioning with cyclophosphamide and fludarabine followed by
      PBSCT from their HLA-matched opposite-sex siblings. Post-transplant bone marrow
      cytogenetics showed full engraftment, and the early post-transplant studies
      demonstrated only normal donor metaphases. Subsequent studies of both patients,
      however, revealed a population of metaphase cells with abnormal, but apparently
      balanced, donor karyotypes. Chromosome studies performed on peripheral blood
      cells collected from both donors after transplantation were normal. Both patients
      remained in clinical remission during follow-up of approximately 8 years in one
      case, and 6 years in the other case, despite the persistence of the abnormal
      clones. Chromosomal abnormalities in residual recipient cells after bone marrow
      or PBSCT are not unusual. In contrast, only rare reports of chromosome
      abnormalities in donor cells exist, all of which have been associated with post
      bone marrow transplant myelodysplastic syndrome or acute leukemias. The present
      cases demonstrate the rare phenomenon of persistent clonal nonpathogenic
      chromosome aberrations in cells of donor origin.

PMID- 19380033
TI  - A novel missense mutation of the XBP1 gene in diffuse large B-cell lymphoma.
AB  - The differentiation of B cells into immunoglobulin-secreting plasma cells is
      controlled by two transcription factors, B lymphocyte-induced maturation protein
      1 (BLIMP1) and X-box-binding protein 1 (XBP1). XBP1 is a positively acting
      transcription factor in the CREB/ATF family that is expressed at a high level in
      plasma cells, and Xbp1-deficient mice were devoid of plasma cells, demonstrating
      that XBP1 is crucial for plasmacytic differentiation. XBP1 acts downstream of
      BLIMP1 and regulates a variety of genes encoding endoplasmic reticulum-associated
      proteins. We have previously reported mutations in the PRDM1 gene (previously
      BLIMP1) in 2 of 15 cases of B-cell lymphoma. Here, we describe a novel mutation
      in the XBP1 gene in 1 of 5 cases of B-cell lymphoma. A single-base substitution
      was found in exon 1 (227G>A) of the XBP1 gene in a patient with diffuse large B
      cell lymphoma, resulting in a somatic missense mutation (R76K). To date, no
      mutations in the XBP1 gene in B-cell lymphoma have been reported. Taken together
      with previous reports, the present results suggest that two key transcription
      factors for the plasmacytic differentiation, XBP1 and BLIMP1, are involved in the
      pathogenesis in diffuse large B-cell lymphoma.

PMID- 19380035
TI  - Images in emergency medicine. Acute airway obstruction as a result of esophageal
      herniation.

PMID- 19380036
TI  - Annals of Emergency Medicine Journal Club. Journal club: Frequent fliers,
      internal and external validity, and the problem with making continuous variables
      binary.

PMID- 19380037
TI  - Sickle cell anemia and pain: will data prevail over beliefs?

PMID- 19380038
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Anaplasma phagocytophilum transmitted through blood transfusion -
      Minnesota 2007.

PMID- 19380039
TI  - Report of the Task Force on Residency Training Information (2008-2009), American
      Board of Emergency Medicine.
AB  - The American Board of Emergency Medicine (ABEM) gathers extensive background
      information on emergency medicine residency training programs and the residents
      in those programs. We present the 2009 annual report on the status of US
      emergency medicine residency programs.

PMID- 19380040
TI  - Evidence-based emergency medicine/rational clinical examination abstract. Is this
      patient clinically depressed?

PMID- 19380041
TI  - Evidence-based emergency medicine/rational clinical examination abstract. Does
      this patient with diabetes have osteomyelitis of the lower extremity?

PMID- 19380042
TI  - Evidence-based emergency medicine/rational clinical examination abstract. Does
      this child have a urinary tract infection?

PMID- 19380043
TI  - Evidence-based emergency medicine/systematic review abstract. Continuing
      education meetings and workshops: effects on professional practice and health
      care outcomes.

PMID- 19380044
TI  - Mama's rules.

PMID- 19380045
TI  - Images in emergency medicine. Lateral rectus palsy from subarachnoid hemorrhage.

PMID- 19380046
TI  - Electrocardiographic research on left bundle branch block must use angiographic
      outcomes and proportionality if it is to guide reperfusion therapy.

PMID- 19380049
TI  - Response to "failure to validate the San Francisco Syncope Rule in an independent
      emergency department population".

PMID- 19380050
TI  - Diagnosis of pulmonary embolism in the emergency department.

PMID- 19380051
TI  - In response to "a prospective, randomized trial of an emergency department
      observation unit for acute onset atrial fibrillation".

PMID- 19380054
TI  - Filming in the emergency department.

PMID- 19380055
TI  - Motor vehicle safety.

PMID- 19380056
TI  - Hand Clinics. Preface.

PMID- 19380057
TI  - Congenital hand differences: embryology and classification.
AB  - Congenital hand differences affect approximately 1 in 500 persons and present
      unique diagnostic and classification challenges. The embryology of the hand and
      upper extremity is discussed, including the molecular basis for patterning of the
      upper limb. The Swanson/International Federation of Societies for Surgery of the
      Hand classification system is described, along with a discussion of the
      difficulties in classifying congenital hand differences based on morphology or
      etiology.

PMID- 19380058
TI  - Congenital failure of formation of the upper limb.
AB  - This article provides an overview of the various classification systems for
      radial longitudinal, central longitudinal, and ulnar longitudinal deficiencies.
      It looks specifically at radius deficiency, hypoplastic thumb, index finger
      pollicization, narrowed thumb web, forearm-elbow deformities, and hand
      abnormalities. Various surgical approaches to these conditions and their results
      are explored. The authors conclude that longitudinal failure of formation
      deformities comprises a substantial portion of the anomalies of the upper limb.
      Although much of the past and current congenital hand literature has been devoted
      to these conditions, they continue to be a reconstructive challenge to hand
      surgeons involved in their care.

PMID- 19380059
TI  - Failure of differentiation part I: Syndactyly.
AB  - Syndactyly is one of the two most common congenital hand anomalies, the other
      being polydactyly. Traditionally, syndactyly is considered simple when only skin
      is involved; complex when there is bone connection; complete when the web
      involvement includes the nail folds; incomplete or partial when the nail folds
      are not involved, but when the web depth is distal to its normal position; and
      complicated when there are multiple tissue abnormalities. This article discusses
      the various types of syndactyly, the current state of known genetic mechanisms,
      and the author's preferred surgical techniques for correction.

PMID- 19380060
TI  - Failure of differentiation: Part II (arthrogryposis, camptodactyly, clinodactyly,
      madelung deformity, trigger finger, and trigger thumb).
AB  - The term "failure of differentiation" describes the phenotypes of a large number
      of otherwise unrelated conditions. The six conditions described here
      (arthrogryposis, camptodactyly, clinodactyly, Madelung deformity, trigger finger,
      and trigger thumb) are believed to occur because various structures failed to
      differentiate normally; however, they have neither common features nor a common
      cause. We have included information about the history and diagnosis of these
      conditions, the cause (if known), and the current concepts of treatment and
      expected outcomes.

PMID- 19380061
TI  - Duplication.
AB  - Congenital limb duplications include pre- and post-axial polydactyly, central
      polydactyly, and the mirror-hand spectrum. Treatment of these duplications
      constitutes a significant functional and aesthetic challenge for the
      reconstructive hand surgeon. This article provides an inclusive review of the
      embryologic and molecular mechanisms underlying these deformities and focuses on
      their clinical treatment. The anatomic variation, classification, surgical
      treatment, and outcomes of surgical intervention are reviewed for each of the
      disorders of duplication.

PMID- 19380062
TI  - Overgrowth conditions: a diagnostic and therapeutic conundrum.
AB  - Over the past five decades, one of the major problems in the treatment of
      overgrowth syndromes of the hand has been classification. Currently, a number of
      specific conditions with known natural histories have been delineated and
      reviewed. Treatment is highly individualized. Amputation is still recommended for
      grotesque deformities of the upper limb. Early aggressive surgery, when
      indicated, will improve contour, function, and appearance. Specific therapeutic
      techniques include radical debulking, microvascular neurolysis, vascular
      reconstruction, epiphysiodesis, and, in some cases, thumb or digit replacement.
      Long-term outcomes remain in the good-to-fair range and are dependent upon the
      condition, reconstructive techniques employed, age of patient, and the severity
      of deformity.

PMID- 19380063
TI  - Undergrowth: brachydactyly.
AB  - Brachydactyly simply means "short finger", but it has a clinical spectrum ranging
      from minor digital hypoplasia to complete aplasia. The index and small fingers
      are the most commonly affected digits, and the middle phalanx is the most
      commonly affected bone. Presentation of brachydactyly is highly variable-a digit
      may be just slightly shorter because of reduced growth of one phalanx or the
      metacarpal, or there may be complete absence of one or more phalanges, or there
      may be complete aplasia of the digit or multiple digits. This article discusses
      the results of conventional reconstruction using nonvascularized toe phalangeal
      bone grafting and distraction lengthening and the newer technique of
      microsurgical toe-to-hand transfers.

PMID- 19380064
TI  - Constriction band syndrome.
AB  - Constriction band syndrome is an uncommon congenital abnormality with multiple
      disfiguring and disabling manifestations. Early amnion rupture with subsequent
      entanglement of fetal parts by amniotic strands is currently the primary theory
      for the development of this syndrome. Management of constriction band syndrome is
      focused on improving function and development while providing a more acceptable
      esthetic appearance. The treatment should be tailored to the individual. Timing
      of repair and surgical planning are important to provide the best functional
      results for affected hands.

PMID- 19380065
TI  - Generalized skeletal abnormalities.
AB  - Given the complexity and diversity of congenital differences, a separate and
      broad category of generalized skeletal abnormalities was proposed to include all
      conditions that are unable to be neatly packaged into the other categories. Some
      of the conditions included in this category are obscure, whereas others are more
      common. Some conditions listed in this section may fit into other categories but
      may be considered as part of the overall classification scheme. This article
      presents congenital trigger finger, congenital clasped thumb, Madelung's
      deformity, and other skeletal hand deformities that are characteristic of
      generalized bone and connective tissue disorders, including achondroplasia and
      Marfan syndrome.

PMID- 19380066
TI  - Congenital differences about the elbow.
AB  - The elbow is frequently affected by congenital differences that limit flexion
      extension and supination-pronation. The limitation can occur in utero or develop
      over time. Delayed causes usually gradually disrupt the anatomy and function of
      the paired bone forearm. Accurate diagnosis is based on a careful examination and
      perusal of radiographs. Certain diagnoses can be helped by surgery and will
      result in improved limb usage and function. In contrast, other diagnoses are
      recalcitrant to modern operative techniques but will benefit from occupational
      therapy and adaptive equipment to enhance independence and activities essential
      to daily life. This article discusses diagnosis and treatment of synostosis,
      arthrogryposis, pterygium, multiple hereditary exostosis, and the unsalvageable
      forearm.

PMID- 19380067
TI  - Congenital hand surgery: what's new and what's coming.
AB  - Congenital hand surgery has advanced during the last 10 years with surgical
      technique improvements, the incorporation of new technologies, and an enhanced
      understanding of the basic pathology of upper extremity anomalies. This article
      reviews the literature with a survey of 70 articles from seven leading journals
      published in the last 12 years. The author concludes that the next decade should
      be even more exciting with the incorporation of an improved understanding of
      tissue engineering and molecular genetics into classification and treatment
      algorithms. Understanding the genetic pathways of normal, and therefore abnormal,
      development should allow improved classification schemes and intervention to
      prevent, modify, or remedy these birth abnormalities.

PMID- 19380068
TI  - Human fetal brain chemistry as detected by proton magnetic resonance
      spectroscopy.
AB  - Magnetic resonance spectroscopy represents an invaluable tool for the in vivo
      study of brain development at the chemistry level. Whereas magnetic resonance
      spectroscopy has received wide attention in pediatric and adult settings, only a
      few studies were performed on the human fetal brain. They revealed changes
      occurring throughout gestation in the levels of the main metabolites detected by
      proton magnetic resonance spectroscopy (N-acetylaspartate, choline, myo-inositol,
      creatine, and glutamate), providing a reference for the normal metabolic brain
      development. Throughout the third trimester of gestation, N-acetylaspartate
      gradually increases, whereas choline undergoes a slow reduction during the
      process of myelination. Less clear are the modifications in creatine, myo
      inositol, and glutamate levels. Under conditions of fetal distress, the meaning
      of lactate detection is unclear, and further studies are needed. Another field
      for investigation involves the possibility of early detection of glutamate levels
      in fetuses at risk for hypoxic-ischemic encephalopathy, because the role of
      glutamate excitotoxicity in this context is well-established. Because metabolic
      modifications may precede functional or morphologic changes in the central
      nervous system, magnetic resonance spectroscopy may likely serve as a powerful,
      noninvasive tool for the early diagnosis and prognosis of different pathologic
      conditions.

PMID- 19380069
TI  - Benign neonatal sleep myoclonus: history and semiology.
AB  - Benign neonatal sleep myoclonus is a condition characterized by myoclonus
      occurring during sleep. Reported here are 18 cases of infants who had
      electroencephalographic monitoring, with myoclonic events recorded in 17 cases.
      In all cases, onset was within days to a few weeks of birth. In no case was the
      diagnosis of sleep myoclonus considered by the referring primary care physician.
      Myoclonus was evident during sleep in all 18 infants, but in two of them it was
      observed also during the transition from sleep to awakening. The behavioral
      features of the disorder were more varied than previously described: four of the
      infants had lateralized myoclonus and two had myoclonus involving the head and
      face. In most of the children, the duration of myoclonus was brief, but in two
      cases the paroxysmal events lasted more than 30 minutes. None of the children had
      electroencephalographic abnormalities during the myoclonus. The condition was
      short-lived, with the myoclonus resolving in most children within 3 months of
      onset. Benign neonatal sleep myoclonus is an under-recognized condition but one
      that has a consistently favorable outcome. Infants with the condition should not
      be treated with antiepileptic drugs.

PMID- 19380070
TI  - Pregabalin: preliminary experience in intractable childhood epilepsy.
AB  - Pregabalin is a new antiepileptic drug that acts at presynaptic calcium channels,
      modulating neurotransmitter release. We report on treating consecutive children
      with severe drug-resistant epilepsy in a prospective, open-label, add-on trial.
      Nineteen children (63% male) aged 4-15 years (mean, 9.7; S.D., 2.9) were
      included. Most (74%) had daily seizures that failed multiple drugs (mean, 5).
      Epilepsy was symptomatic in 58%, and 74% exhibited associated cognitive deficits.
      Seizures were mixed in nine (47%), and four (21%) manifested Lennox-Gastaut
      syndrome. Pregabalin was maintained at 150-300 mg/day. On pregabalin, one (6%)
      child became seizure-free, and seven (37%) had >50% seizure reduction. The
      percentage of children with daily seizures was reduced from 74% before pregabalin
      to 37% afterward (P < 0.002). Side effects were evident in six (32%) with
      somnolence, weight gain, dizziness, or behavioral change. The drug was withdrawn
      in five (26%) children for lack of efficacy, and in two (11%) for worsening of
      myoclonic epilepsy. We conclude that pregabalin is a useful addition in the
      treatment of refractory childhood epilepsy. The drug should be used with caution
      in myoclonic epilepsy. Controlled studies are needed to establish long-term
      efficacy and tolerability.

PMID- 19380071
TI  - Pediatric mitochondrial respiratory chain disorders in the Centro region of
      Portugal.
AB  - The present study reviewed mitochondrial respiratory chain disorders diagnosed at
      the sole tertiary pediatric hospital in the Centro region of Portugal and
      estimated incidence and prevalence in this region. The Bernier criteria were used
      to retrospectively classify 200 children investigated from 1997 to 2006. A total
      of 78 patients were assigned with definite primary mitochondrial disorder, two
      thirds presenting in the first year of life. At presentation, 61 children had
      neuromuscular symptoms. Neurologic, ophthalmologic, growth retardation, muscular,
      cardiac, respiratory, hepatic, hematologic, and digestive symptoms were the most
      frequent clinical features. A classic mitochondrial syndrome was identified in 12
      children, 6 of them with Leigh syndrome. Major respiratory chain enzymatic
      defects were detected in 73 cases. Pathogenic mitochondrial DNA or nuclear DNA
      mutations (or both) were observed in 9 children. Mortality was 29.5%, with median
      age of death at 8 months. Survival was shorter for patients with onset at infancy
      or children with liver or cardiac involvement, or with lactic acidosis. Estimated
      incidence of mitochondrial disorders in children less than 10-years-old was
      1.5/10,000, and point prevalence was 5.4/100,000, respectively. These disorders
      seem to have a high incidence and poor prognosis in the Centro region of
      Portugal.

PMID- 19380072
TI  - A clinical study of Sotos syndrome patients with review of the literature.
AB  - Sotos syndrome is characterized by tall stature, advanced bone age, typical
      facial abnormalities, and developmental delay. The associated gene is NSD1. The
      study involved 22 patients who fulfilled the clinical criteria. Phenotypic
      characteristics, central nervous system findings, and cardiovascular and urinary
      tract abnormalities were evaluated. Meta-analysis on the incidence of cardinal
      clinical manifestations from the literature was also performed. Macrocephaly was
      present in all patients. Advanced bone age was noted in 14 of 22 patients (63%),
      and its incidence presented significant statistical difference in the meta
      analysis of previous studies. Some patients had serious clinical manifestations,
      such as congenital heart defects, dysplastic kidneys, psychosis, and leukemia.
      Clinical and laboratory examinations should be performed to prevent and manage
      any unusual medical aspect of the syndrome. Facial gestalt and macrocephaly,
      rather than advanced bone age, are the strongest indications for clinical
      diagnosis.

PMID- 19380073
TI  - Early-onset neurodegenerative disease of the cerebellum and motor axons.
AB  - We describe a novel hereditary neurodegenerative disease of infancy affecting an
      Aboriginal family from northern Manitoba, Canada. The parents are
      nonconsanguineous, without a family history of neurodegenerative diseases. Four
      of 10 siblings (three males and one female) presented with neurologic
      abnormalities including arthrogryposis, seizures, and severe developmental delay
      shortly after birth. In two children, cerebellar atrophy and mild cerebral
      atrophy were documented on neuroimaging. Two children, a boy who died at age 40
      months and a girl who died at age 22 months, underwent muscle biopsies at 3 weeks
      and 4 months of age, respectively. The biopsies revealed fiber-size variability
      in the boy, and grouped atrophy with fiber-type grouping in the girl. Two boys
      who died at ages 7.5 and 37 months underwent autopsies that indicated severe
      atrophy of the cerebellar hemispheres (especially the inferior lobules and
      vermis), hypomyelination of white-matter fascicles in the striatum, severe
      atrophy of corticospinal tracts in the brainstem and spinal cord, and atrophy of
      the anterior spinal roots. In the spinal cord, motor neuron cell bodies and the
      posterior columns were spared. This clinical entity likely represents a novel
      neurodegenerative disease of the cerebellum and long motor axons.

PMID- 19380074
TI  - Pseudotumor cerebri secondary to subacute sclerosing panencephalitis.
AB  - Unusual presentations are not rare in subacute sclerosing panencephalitis. Five
      patients initially diagnosed with pseudotumor cerebri were ultimately determined
      to have pseudotumor cerebri secondary to subacute sclerosing panencephalitis. The
      present study retrospectively reviewed 56 cases history, neurologic symptoms, and
      clinical and laboratory data, as well as the outcomes. On admission, five
      patients (group 1) presenting with pseudotumor cerebri exhibited bilateral
      papilledema, and in each of them cranial magnetic resonance imaging revealed
      small lateral ventricles, effacement of the subarachnoid space, and no mass
      lesion. On admission, 51 patients (group 2) had no pseudotumor cerebri findings.
      The year of original measles infection, the interval between measles and onset of
      subacute sclerosing panencephalitis, and initial neurologic symptoms were
      similar, but length of symptoms before diagnosis of subacute sclerosing
      panencephalitis was shorter in group 1, and the clinical stage of subacute
      sclerosing panencephalitis on admission was more advanced in group 2.
      Cerebrospinal fluid mean open pressure was 378 +/- 22 H(2)O in group 1 and 146 +/
      28 H(2)O in group 2; cerebrospinal fluid antibody was 2038 +/- 768 U/L in group
      1 and was 664 +/- 214 U/L in group 2. Only three of the five patients with
      pseudotumor cerebri had typical periodic discharges on electroencephalographic
      examination. These findings suggest that subacute sclerosing panencephalitis can
      cause pseudotumor cerebri.

PMID- 19380075
TI  - MRI of pneumorachis in a newborn infant with open myelomeningocele.
AB  - Pneumorachis, or air within the spinal canal, is a very rare radiographic
      finding, frequently of traumatic origin. A newborn infant with an open
      lumbosacral myelomeningocele presented with severe paraparesis and an unexpected
      dysfunction of the brainstem with somnolence, irregular respiration, and motor
      deficits of the upper extremities. Magnetic resonance imaging revealed hypoplasia
      of the brainstem and cerebellum and low-signal lesions on T(2)-weighted images at
      the cervicocranial junction, in the lateral ventricles, and in the spinal canal.
      Computed tomography confirmed the presence of intracranial and intraspinal air.
      The air disappeared 2 weeks later according to magnetic resonance imaging, but no
      clinical improvement occurred, even after 6 months. Pneumorachis and
      pneumocephalus can occur in newborn infants as an unexpected complication of an
      open myelomenigocele, with or without signs. The radiographic appearance of
      intraspinal air on magnetic resonance imaging was not described previously.

PMID- 19380076
TI  - Isolated cranial nerve enhancement in metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy is a lysosomal storage disorder with an estimated
      incidence of 1:40,000. Magnetic resonance imaging at time of diagnosis often
      shows symmetric white matter involvement, sparing the arcuate fibers. A 25-month
      old female child presented with a cranial neuropathy, a spastic gait, decreased
      leukocyte arylsulfatase-A activity, and elevated urinary sulfatides. Magnetic
      resonance imaging revealed multiple cranial nerve enhancement, without
      intraparenchymal white matter involvement.

PMID- 19380077
TI  - Pigmentary mosaicism, subcortical band heterotopia, and brain cystic lesions.
AB  - A 10-year-old boy presented with a severe and diffuse mosaic skin
      hypopigmentation running (in narrow bands) along the lines of Blaschko associated
      with mosaic areas of alopecia, facial dysmorphism with midface hypoplasia,
      bilateral punctate cataract, microretrognathia, short neck, pectus excavatum,
      joint hypermobility, mild muscular hypotonia, generalized seizures, and mild
      mental retardation. Cranial magnetic resonance imaging revealed hypoplastic
      corpus callosum (primarily posterior), subcortical band heterotopia, and diffuse
      subcortical, periventricular cystic-like lesions. Similar dysmorphic features
      were observed in the child's mother, but with no imaging abnormalities. The
      facial phenotype coupled with the cysts in the brain was strongly reminiscent of
      the oculocerebrorenal Lowe syndrome. Full chromosome studies in the parents and
      the proband and mutation analysis on peripheral blood lymphocytes (and on skin
      cultured fibroblasts from affected and unaffected skin areas in the child) in the
      genes for subcortical band heterotopia (DCX (Xq22.3-q23)], lissencephaly
      (PAFAH1B1, alias LIS1, at 17p13.3), and oculocerebrorenal syndrome of Lowe (OCRL
      at Xq23-q24)] were unrevealing. This constellation of multiple congenital
      anomalies including skin hypopigmentation and eye, musculoskeletal, and nervous
      system abnormalities was sufficiently characterized to be regarded as a novel
      example of pigmentary mosaicism of the Ito type (i.e., hypomelanosis of Ito).

PMID- 19380078
TI  - Benign familial neonatal convulsions: novel mutation in a newborn.
AB  - Benign familial neonatal convulsions are a rare, autosomal-dominant form of
      neonatal epileptic syndrome. It can occur 1 week after birth, and usually
      involves frequent episodes, but with a benign course. The diagnosis depends on
      family history and clinical features. The mutant gene locates at 20q13, a voltage
      gated potassium-channel gene (KCNQ2). Our patient exhibited an uneventful
      delivery course and onset of seizures at age 2 days. The general tonic seizures
      were unique and asymmetric, with frequencies of >20 per day. Results of
      examinations were within normal limits, including biochemistry and brain magnetic
      resonance imaging. Abnormalities included a small ventricular septum defect on
      cardiac sonography unrelated to the seizures, and nonspecific, multiple, high
      voltage sharp waves and spike waves occurring infrequently in the central region
      on electroencephalogram. After phenobarbital and phenytoin use, the seizures
      persisted. On day 12, another antiepileptic drug, vigabatrin (unavailable in the
      United States), was used, and seizures decreased. A novel mutation of KCNQ2 was
      identified from a blood sample. The baby had occasional seizures with drug
      treatment at age 3 months. Benign familial neonatal convulsion should be
      considered in a baby with a unique seizure pattern and positive family history.
      Genetic counseling and diagnosis are mandatory.

PMID- 19380079
TI  - Life-threatening organ failure after lamotrigine therapy.
AB  - We describe an 11-year-old girl with a seizure disorder who developed fever,
      rash, rhabdomyolysis, and multiorgan failure 2 weeks after commencing a
      transition from sodium valproate to lamotrigine therapy. To our knowledge, this
      patient represents the most severe life-threatening hypersensitivity lamotrigine
      reaction described in the pediatric literature. We recommend caution when
      prescribing lamotrigine to children on concomitant sodium valproate, and
      immediate discontinuation of lamotrigine and the provision of aggressive
      supportive care in patients with features of lamotrigine hypersensitivity.

PMID- 19380080
TI  - Hypomelanosis of Ito and Sturge-Weber syndrome without facial nevus: an
      association or a new syndrome?
AB  - Sturge-Weber syndrome without facial nevus is rare. Twenty-four cases were
      previously reported. Although hypomelanosis of Ito is a relatively common
      disorder, there was only one previous case in association with Sturge-Weber
      syndrome. We describe an 11-year-old boy with Sturge-Weber syndrome without
      facial nevus, coexistent with hypomelanosis of Ito.

PMID- 19380081
TI  - Pneumocephalus: a rare presentation of Candida sphenoid sinusitis.
AB  - Pneumocephalus is uncommon and usually evident after head trauma or surgery. It
      is a rare complication of acute, isolated sphenoid sinusitis caused by fungus
      pathogens in an immunocompetent patient. We report on a 14-year-old healthy boy
      with acute, isolated sphenoid sinusitis caused by Candida albicans.
      Pneumocephalus was the initial overlooked presentation. Although uncommon, fungal
      disease should be considered in acute, isolated sphenoid sinusitis when
      pneumocephalus is discovered, even in immunocompetent patients. Failure to
      diagnose and treat this entity promptly usually results in rapid progression and
      death.

PMID- 19380082
TI  - Neurobrucellosis: a partially treatable cause of vision loss.
AB  - Involvement of the central nervous system due to brucellosis is rare and has a
      broad range of clinical manifestations. Reported here is a case of
      neurobrucellosis in a 13-year-old boy leading to visual impairment and unilateral
      hearing loss. Cranial magnetic resonance imaging revealed a suprasellar mass with
      extension to the optic chiasm. This case represents a novel finding of pediatric
      neurobrucellosis involving the optic chiasm. The patient's visual acuity, but not
      hearing, improved after initiation of antibiotic therapy.

PMID- 19380083
TI  - Epileptic spasms after stem cell transplantation for chronic Epstein-Barr virus
      infection.
AB  - Stem cell transplantation has been performed for various diseases, contributing
      to a markedly improved prognosis in some cases. However, several complications,
      including posterior reversible encephalopathy syndrome, have been evident.
      Although posterior reversible encephalopathy syndrome was originally defined as a
      reversible disease, it has become clear that it is not reversible in all
      patients. Epstein-Barr virus causes a wide spectrum of neurologic disorders,
      including epilepsy. To our knowledge, Epstein-Barr virus was not previously
      reported to cause epileptic spasms. We describe a girl with epileptic spasms
      after posterior reversible encephalopathy syndrome associated with stem cell
      transplantation for chronic Epstein-Barr virus infection. Although direct
      correlation was not clarified, this is a rare case that may contribute to our
      understanding of the neurologic complications of stem cell transplantation for
      chronic Epstein-Barr virus infection.

PMID- 19380084
TI  - MRS is the test of choice for detecting and monitoring disorders of creatine
      metabolism.

PMID- 19380085
TI  - Meningiomas in children.

PMID- 19380086
TI  - Health economic decision making in Europe--a new priority for breast cancer
      advocacy.
AB  - The lay public, patients and advocates are not usually aware of how decisions are
      made by health systems, insurers, or governments concerning the availability of
      medicines provided through national health systems. Today a variety of health
      economic analyses are undertaken to determine if a particular therapy is cost
      effective and meets specific criteria to be covered under the national health
      service programmes. This decision making process is complicated, and in some
      countries the methodology used is not transparent; these decisions are not
      adopted in the same way in all countries and often there is no communication or
      approval required by the public or patient representatives. This is not
      acceptable from the patient's perspective as effectiveness must remain the
      criteria and these decisions must be understood and shared in such a way that all
      stakeholders agree on guidelines for the approval and delivery of new medicines.
      Other solutions that impact cost need to be explored--new methods of raising
      funds for research, public health prevention programmes to reduce the burden in
      future years and increasing health budgets by taxing items that contribute to the
      cancer burden such as tobacco and alcohol.

PMID- 19380087
TI  - Trends in sexual experience, contraceptive use, and teenage childbearing: 1992
      2002.
AB  - PURPOSE: To examine how cohort trends in family, individual, and relationship
      characteristics are linked to trends in adolescent reproductive health outcomes
      to provide a better understanding of factors behind recent declines in teenage
      birth rates. METHODS: We examine a sample of three cohorts of females and males
      aged 15-19 in 1992, 1997, and 2002, based on retrospective information from the
      2002 National Survey of Family Growth. We identify how family, individual, and
      relationship characteristics are associated with the transition to sexual
      intercourse, contraceptive use at first sex, and the transition to a teen birth.
      RESULTS: Cohort trends and multivariate analyses indicate changes in family and
      relationship characteristics among American teens have been associated with
      positive trends in reproductive health since the early 1990s. Factors associated
      with improvement in adolescent reproductive health include positive changes in
      family environments (including increases in parental education and a reduced
      likelihood of being born to a teen mother) and positive trends in sexual
      relationships (including an increasing age at first sex and reductions in older
      partners). These positive trends may be offset, in part, by negative changes in
      family environments (including an increased likelihood of being born to unmarried
      parents) and the changing racial/ethnic composition of the teen population.
      CONCLUSIONS: Recent increases in the U.S. teen birth rate highlight the continued
      importance of improving reproductive health outcomes. Our research suggests that
      it is important for programs to take into consideration how family, individual,
      and relationship environments influence decision-making about sex, contraception,
      and childbearing.

PMID- 19380088
TI  - Self-weighing and weight control behaviors among adolescents with a history of
      overweight.
AB  - PURPOSE: To assess the relationships between self-weighing frequency, weight
      control behaviors, and weight status among male and female adolescents who have a
      history of being overweight. METHODS: This study compared weight control
      behaviors between two groups of adolescents with a history of being overweight
      (body mass index [BMI] >85th percentile): those who weighed themselves weekly or
      more (frequent self-weighers) and those who weighed themselves monthly or less
      (infrequent self-weighers). Participants completed a survey on weight control
      behaviors, dietary intake, physical activity, and sedentary activity. Height and
      weight were also measured. Logistic regression analyses were used for categorical
      outcomes and linear regressions for continuous outcomes. RESULTS: Of the 130
      adolescents, 43% were frequent weighers and 57% were infrequent weighers. In
      comparison to infrequent self-weighers, frequent self-weighers were more likely
      to report using behavior change strategies, following a structured diet, and
      engaging in healthy weight control behaviors, especially decreasing caloric
      intake, high fat food intake, and "junk food" intake. Also, more frequent self
      weighers reported engaging in more strenuous physical activity and spending less
      time playing videogames than infrequent self-weighers. Although not significant,
      a trend resulted indicating lower average BMI percentile among frequent self
      weighers. No significant differences were found between the two groups in
      unhealthy weight control behaviors. CONCLUSIONS: These results suggest that
      adolescents with a history of overweight who self-weigh at least weekly are more
      likely to report using healthy weight control behaviors than adolescents who self
      weigh monthly or less frequently. Self-monitoring of weight may be a useful
      component of a comprehensive weight management plan for some overweight
      adolescents.

PMID- 19380089
TI  - Associations between family dinner frequency and specific food behaviors among
      grade six, seven, and eight students from Ontario and Nova Scotia.
AB  - PURPOSE: Family dinner frequency has recently been associated in the literature
      with improved dietary profiles and healthy body weight in children and
      adolescents. However, it is not known whether family dinners are associated with
      other commonly reported food behaviors (fast food and soft drink consumption,
      breakfast skipping, and dieting) and attitudes (body weight concerns and self
      efficacy for healthy eating) among Canadian students in grades 6, 7, and 8.
      METHODS: A total of 3223 participants from Northern Ontario (Porcupine Region),
      Southern Ontario (Peel Region, Region of Waterloo, Toronto District), and Nova
      Scotia completed the Food Behavior Questionnaire during the 2005-2006 academic
      school year. Ordinal logistic regression analyses were used to determine the
      associations between family dinner frequency and food behaviors and attitudes.
      RESULTS: Higher family dinner frequency was significantly associated with less
      soft drink consumption, consuming breakfast on the day of the survey, the absence
      of a high body weight concern, having higher self-efficacy for healthy eating
      when at home with family, and during social times with friends. CONCLUSIONS:
      Researchers and clinicians should be aware of these associations when planning
      family based healthy eating strategies.

PMID- 19380090
TI  - Acceptance of the HPV vaccine for adolescent girls: analysis of state-added
      questions from the BRFSS.
AB  - PURPOSE: Previous research regarding human papillomavirus (HPV) awareness and
      vaccine acceptance has relied on convenience or other selected samples of the
      population. To assess the prevalence of HPV awareness and vaccine acceptance in
      Kentucky we added questions to the 2006 Kentucky Behavioral Risk Factor Survey
      System (BRFSS), a population-based survey of health behaviors. METHODS: Women who
      participated in the statewide BRFSS were asked two HPV-related questions: one
      assessed previous awareness of HPV, and another assessed vaccine acceptance for
      girls 10 to 15 years old. We used crosstabulations and multivariate logistic
      regression to determine which factors were associated with HPV awareness and
      vaccine acceptance. Because the HPV vaccine Gardasil was approved in June 2006,
      we conducted an analysis of pre- and postapproval HPV awareness and vaccine
      acceptance. We also compared results across Appalachian and non-Appalachian
      counties, two distinct regions of Kentucky. RESULTS: Overall, 57.6% of women had
      heard of HPV, and 70.2% accepted vaccination for girls. HPV awareness increased
      after Gardasil's approval, but the increase was much smaller among Appalachian
      women. Prevalence of vaccine acceptance was unchanged in both regions. Awareness
      of HPV was not associated with vaccine acceptance, and factors significantly
      associated with vaccine acceptance in multivariate analysis differed by
      Appalachian status. CONCLUSIONS: This population-based survey of Kentucky women
      found relatively high vaccine acceptance for girls. Also, many respondents
      reported not knowing whether they accept vaccination, and factors associated with
      vaccine acceptance varied by Appalachian status. These findings suggest that
      acceptance of the HPV vaccine for girls may improve with targeted interventions.

PMID- 19380092
TI  - Bummed out now, feeling sick later: weekday versus weekend negative affect and
      physical symptom reports in high school freshmen.
AB  - PURPOSE: This study examined adolescent negative affect (NA) in daily life on
      school days and weekend days during the spring and associations with physical
      symptoms during the following summer. METHODS: Using experience sampling
      methodology (ESM), participants provided electronic diary (eDiary) reports of NA
      on weekdays (Thursday and Friday) and weekend days during their 9th grade year.
      In telephone interviews during the winter and summer months they reported
      physical symptoms. Multiple regression analyses were conducted to examine
      associations between weekday NA, weekend NA, and their interaction and four
      constellations of physical symptoms reported in summer (pain, respiratory,
      gastrointestinal, and immune symptoms). RESULTS: Findings indicated that weekend
      NA was associated with later reports of pain, respiratory, and immune symptoms.
      For gastrointestinal symptoms only adolescents who reported low NA on both
      weekend and school days reported fewer gastric symptoms than other adolescents.
      CONCLUSIONS: Mapping the predictors and correlates of weekend NA may be important
      not only for understanding teenage mood patterns but also for enhancing the
      interpretation of physical symptom reporting by adolescents.

PMID- 19380091
TI  - Mothers' and adolescents' beliefs about risk compensation following HPV
      vaccination.
AB  - PURPOSE: To examine the prevalence and predictors of the belief that human
      papillomavirus (HPV) vaccination will result in "risk compensation," that is,
      will increase risky sexual behavior. METHODS: Two surveys were carried out: with
      332 mothers (Study 1) and 360 adolescent girls (Study 2). The outcome measure was
      the score on a risk compensation scale tapping beliefs that HPV vaccination would
      increase risky sexual behavior. RESULTS: Among mothers, those from the lowest
      income group (F = 4.38, p < .01), from ethnic minority backgrounds (F = 7.41, p <
      .01), and who did not attend cervical screening (F = 9.96, p < .01), had the
      highest risk compensation scores. Among adolescents, girls with lower educational
      attainment (F = 4.14, p < .05), from ethnic minority backgrounds (F = 6.60, p <
      .001), and who felt themselves to be less sexually experienced than their peers
      (F = 3.31, p < .05), had the highest scores. Girls showed lower belief in risk
      compensation in relation to their own behavior (personal compensation) than for
      "girls in general" (general compensation; t = 13.68, p < .001). Lower knowledge
      of HPV was associated with higher personal risk compensation beliefs (F = 4.26, p
      < .05). CONCLUSIONS: A significant minority of mothers and adolescents themselves
      say that HPV vaccination would increase the chance of risky sexual behavior.
      Because risk compensation beliefs are likely to predict HPV vaccine acceptance,
      identifying the basis for these beliefs and providing appropriate information and
      education to parents and adolescents will be vital. Following the introduction of
      vaccination, it will be important to discover whether risk compensation actually
      takes place, and every effort should be made to ensure it does not.

PMID- 19380093
TI  - Transitions in suicide risk in a nationally representative sample of adolescents.
AB  - PURPOSE: Suicide is the third leading cause of death among older adolescents, and
      represents a significant public health problem. Preventing suicidal behavior
      depends on an understanding of the developmental transitions in suicide risk and
      whether the likelihood of a suicide attempt can be predicted prospectively.
      METHODS: Data from the National Longitudinal Study of Adolescent Health were used
      for the study. The sample is nationally representative, and includes 10,424 youth
      assessed over three time points spanning 7 years. MPLUS was used to analyze the
      data. RESULTS: Latent class analysis showed that youth could be classified into
      three latent classes representing degree of suicide risk. Indicators of risk
      included depressive symptoms, hopelessness, suicidal ideation, having a family
      history of suicidal behavior, and having a friend history of suicidal behavior.
      Latent transition analyses showed that youth in the low-risk group remained at
      low risk both 1 and 7 years later. Although some youth who were classified as
      high-risk transitioned to a lower risk group 7 years later, a significant
      proportion remained at high risk. Analyses also revealed that the probability of
      making a suicide attempt was higher for youth in the high-risk latent class 1 and
      7 years earlier. CONCLUSIONS: Findings indicate that suicide prevention efforts
      should be targeted primarily at youth at high risk for suicide; most youth
      classified as "low risk" remained at low risk as they transitioned to young
      adulthood.

PMID- 19380094
TI  - Mental disorders in self-cutting adolescents.
AB  - PURPOSE: Self-cutting as a form of self-harm is common in general population
      adolescents. The aim of this study was to investigate the prevalence of mental
      disorders and associated factors among self-cutting community-dwelling
      adolescents. METHODS: A sample of adolescents who reported current self-cutting
      (n = 80) was drawn from a large sample of community adolescents (n = 4205). Of
      these 80 individuals, 44 consented to further detailed assessment. An age- and
      gender-matched control subject was selected for each study subject. Data
      collection included Structured Clinical Interviews for DSM-IV-TR, the Beck
      Depression Inventory, the Alcohol Use Disorders Identification Test (AUDIT), and
      the Youth Self-Report for adolescents aged 11-18 years (YSR). RESULTS: Major
      depressive disorder (63% vs. 5%), anxiety disorders (37% vs. 12%), and eating
      disorders (15% vs. 0%) were more common among self-cutting girls (n = 41) than
      among controls. None of the self-cutting boys (n = 3) had a DSM-IV-TR Axis I
      mental disorder. In multivariate model, the presence of major depressive
      disorder, the AUDIT score and the YSR internalizing subscale score were the
      factors that were independently associated with the presence of self-cutting in
      girls. CONCLUSIONS: Major depressive disorder, signs of alcohol misuse, and
      internalizing behavior strongly associate with self-cutting in community-dwelling
      adolescents, especially in girls.

PMID- 19380095
TI  - Gender differences in socioemotional factors during adolescence and effects of a
      violence prevention program.
AB  - PURPOSE: The study had two aims: 1) to analyze the existence of gender
      differences in socioemotional developmental factors, and 2) to apply a program of
      education for peace and prevention of violence to determine whether the pretest
      posttest change in socioemotional developmental factors differs as a function of
      gender. METHODS: The sample comprised 285 adolescents, aged 15-16 years,
      including 162 experimental subjects and 123 control subjects. An experimental
      design of repeated pre-posttest measures with a control group was used, and four
      assessment instruments were administered. RESULTS: Analyses of variance confirmed
      significantly higher scores in the female adolescents in cognitions of rejection
      of violence, prosocial cognitions, cooperative conflict solving, positive
      strategies for coping with violence, and positive social behaviors. Male
      adolescents obtained significantly higher scores in cognitions of acceptance of
      violence, aggressive conflict solving, aggressive strategies for coping with
      violence, and negative social behaviors. The pre-post change in most of the
      factors of socioemotional development assessed was similar in both sexes.
      CONCLUSIONS: Results suggest the need to reflect on and modify the type of
      childrearing and socialization patterns that are promoted in males so that they
      will favor the development of skills oriented toward warm interpersonal
      relations, nonaggressive communication, positive social behaviors, internal
      control of anger, empathy, etc. Results also suggest including supplementary
      modules for males when designing interventions to prevent violence.

PMID- 19380096
TI  - A prospective study of perception in adolescent smoking.
AB  - PURPOSE: This prospective study examined how environmental smoking affects the
      perception of lifetime smoking prevalence and thereby the likelihood of
      subsequent regular smoking. METHODS: A longitudinal design (N = 6769) with three
      waves was used to test our research questions. Exposure to smoking by peers, best
      friends, and parents were assessed at T1. Perception of lifetime smoking
      prevalence was calculated at T2. Adolescent smoking was assessed at three waves.
      RESULTS: Overestimation of lifetime smoking prevalence was predicted by having a
      predominantly smoking peer group, having a best friend who smokes, and by having
      at least one parent who smokes. In consistency with a false consensus effect,
      smokers were more susceptible to overestimate lifetime smoking prevalence than
      nonsmokers. Subsequently, while controlling for smoking at T2, overestimating
      lifetime smoking prevalence was predictive of regular smoking at T3 (in
      accordance with the conformity hypothesis). Specifically, overestimation of
      lifetime smoking appeared to mediate the effects of environmental smoking (peers,
      best friends, and parents) on adolescent smoking. No support was found for a
      moderation effect of exposure to environmental smoking on the link between
      misperception of lifetime smoking prevalence and regular smoking. CONCLUSIONS:
      The study offers a rare and needed theoretical and empirical research examining
      environmental and individual predictors of regular smoking. Besides direct
      prevention of exposure to smoking, cognitions that are a product of exposure to
      smoking need to be addressed in prevention campaigns.

PMID- 19380097
TI  - Spiritual well-being and mental health outcomes in adolescents with or without
      inflammatory bowel disease.
AB  - PURPOSE: The purpose of this study was threefold: 1) to describe spiritual well
      being (existential and religious well-being) in adolescents with inflammatory
      bowel disease (IBD) versus healthy peers; 2) to examine associations of spiritual
      well-being with mental health outcomes (emotional functioning and depressive
      symptoms); and 3) to assess the differential impact of existential versus
      religious well-being on mental health. METHODS: A total of 155 adolescents aged
      11-19 years from a children's hospital and a university hospital filled out
      questionnaires including the Spiritual Well-Being Scale, the Children's
      Depression Inventory-Short Form, and the Pediatric Quality of Life Inventory.
      Covariates in multivariable models included demographics, disease status, and
      interactions. RESULTS: Participants' mean (SD) age was 15.1 (2.0) years; 80 (52%)
      were male; and 121 (78%) were of white ethnicity. Levels of existential and
      religious well-being were similar between adolescents with IBD and healthy peers.
      In multivariable analyses, existential well-being was associated with mental
      health (partial R(2) change = .08-.11, p < .01) above and beyond other
      characteristics (total R(2) = .23, p < .01). Presence of disease moderated both
      the relationship between existential well-being and emotional functioning and
      that between religious well-being and depressive symptoms: that is, the
      relationships were stronger in adolescents with IBD as compared with healthy
      peers. Religious well-being was only marginally significantly associated with
      mental health after controlling for other factors. CONCLUSIONS: Although both
      healthy adolescents and those with IBD had high levels of spiritual well-being,
      having IBD moderated the relationship between spiritual well-being and mental
      health. Meaning/purpose was related to mental health more than was connectedness
      to the sacred.

PMID- 19380099
TI  - Early markers of pubertal onset: height and foot size.
AB  - This longitudinal study compared the timing of foot and height velocities with
      pubertal onset in girls. There was no difference between ages of increased foot
      and height growth velocities; both occurred before onset of secondary sexual
      characteristics. Change in foot size may represent an early marker for transition
      to puberty.

PMID- 19380098
TI  - Patterns of adolescent physical activity, screen-based media use, and positive
      and negative health indicators in the U.S. and Canada.
AB  - PURPOSE: To examine: (1) how adolescent physical activity (PA) and screen-based
      media use (SBM) relate to physical and social health indicators, and (2)
      crossnational differences in these relationships. METHODS: Essentially identical
      questions and methodologies were used in the Health Behavior in School-Aged
      Children cross-sectional surveys of nationally representative samples of American
      (N = 14,818) and Canadian (N = 7266) students in grades 6 to 10. Items included
      questions about frequency of PA, SBM, positive health indicators (health status,
      self-image, quality of life, and quality of family and peer relationships), and
      negative health indicators (health complaints, physical aggression, smoking,
      drinking, and marijuana use). RESULTS: In regression analyses controlling for age
      and gender, positive health indicators were uniformly positively related to PA
      while two negative health indicators were negatively related to PA. However, PA
      was positively related to physical aggression. The pattern for SBM was generally
      the opposite; SBM was negatively related to most positive health indices and
      positively related to several of the negative health indicators. The notable
      exception was that SBM was positively related to the quality of peer
      relationships. Although there were crossnational differences in the strength of
      some relationships, these patterns were essentially replicated in both countries.
      CONCLUSIONS: Surveys of nationally representative samples of youth in two
      countries provide evidence of positive physical and social concomitants of PA and
      negative concomitants of SBM. These findings suggest potential positive
      consequences of increasing PA and decreasing SBM in adolescents and provide
      further justification for such efforts.

PMID- 19380100
TI  - Assessment of body mass index and association with adolescent preventive care in
      U.S. outpatient settings.
AB  - Using data from the latest National Ambulatory Care Surveys, this study finds
      that the importance of assessment of overweight and obesity and preventive
      counseling in adolescents is underappreciated in outpatient practices throughout
      the United States. The room for improvement remains considerable, and
      interventions to promote quality preventive care are needed for all adolescents.

PMID- 19380101
TI  - Misuse of over-the-counter cough or cold medications among adolescents:
      prevalence and correlates in a national sample.
AB  - The current research examines the misuse of over-the-counter cough/cold
      medications among adolescents with data from the 2006 National Survey on Drug Use
      and Health. Findings indicate that age, gender, family income, physical and
      mental health, and the use of alcohol and other drugs are correlates of the
      misuse of over-the-counter cough/cold medications.

PMID- 19380102
TI  - Sexual violence and reproductive health among youth in Port-au-Prince, Haiti.
AB  - We examine sexual violence and reproductive health outcomes among sexually
      experienced youth in Port-au-Prince, Haiti, using the Priorities for Local AIDS
      Control methodology to identify participants in locations where sexual
      partnerships are formed. Our findings indicated that sexual violence is common
      and is significantly associated with condom use, pregnancy experience, and recent
      sexually transmitted infection symptoms.

PMID- 19380104
TI  - Gender identity disorder in children and adolescents. Foreword.

PMID- 19380103
TI  - Chemical crosslinking studies with the mouse Kcc1 K-Cl cotransporter.
AB  - Oligomerization, function, and regulation of unmodified mouse Kcc1 K-Cl
      cotransporter were studied by chemical crosslinking. Treatment of Xenopus oocytes
      and 293T cells expressing K-Cl cotransporter Kcc1 with several types of chemical
      cross-linkers shifted Kcc1 polypeptide to higher molecular weight forms. More
      extensive studies were performed with the amine-reactive disuccinyl suberate
      (DSS) and with the sulfhydryl-reactive bis-maleimidohexane (BMH). Kcc1 cross
      linking was time-dependent in intact oocytes, and was independent of protein
      concentration in detergent lysates from oocytes or 293T cells. Kcc1 cross-linking
      by the cleavable cross-linker DTME was reversible. The N-terminal and C-terminal
      cytoplasmic tails of Kcc1 were not essential for Kcc1 crosslinking. PFO-PAGE and
      gel filtration revealed oligomeric states of uncrosslinked KCC1 corresponding in
      mobility to that of cross-linked protein. DSS and BMH each inhibited KCC1
      mediated (86)Rb(+) uptake stimulated by hypotonicity or by N-ethylmaleimide (NEM)
      without reduction in nominal surface abundance of KCC1. These data add to
      evidence supporting the oligomeric state of KCC polypeptides.

PMID- 19380105
TI  - Gender identity disorder in children and adolescents.

PMID- 19380106
TI  - Mechanisms of drug efflux and strategies to combat them. Preface.

PMID- 19380107
TI  - Ubiquitination - a bacterial effector's ticket to ride.
AB  - Ubiquitination has many important cellular functions, including regulation of
      plasma membrane endocytosis. In their recent article in Cell, Patel et al. (2009)
      show that the activity of the multifunctional Salmonella virulence protein SopB
      is controlled by ubiquitin-dependent delivery from the plasma membrane to the
      Salmonella-containing vacuole.

PMID- 19380108
TI  - Th17 cells bounce off the fungal wall.
AB  - Th17 cells are thought to play a pivotal role in defenses against Candida
      albicans. van de Veerdonk et al. (2009) investigate components of the fungal cell
      wall and their cognate receptors on human peripheral blood mononuclear cells
      (PBMCs) responsible for IL-17 production and find a predominant role for mannan
      stimulation of the mannose receptor.

PMID- 19380109
TI  - The tangled web of signaling in innate immunity.
AB  - Similarities in innate immune signaling exist between mammals and the nematode
      Caenorhabditis elegans. Now, Ziegler et al. (2009) and Ren et al. (2009)
      demonstrate that a protein kinase C delta homolog in C. elegans is involved in
      innate immunity, providing evidence that the conservation of immune signaling
      networks extends further than previously thought.

PMID- 19380110
TI  - All for one and one for all: herpesviral microRNAs close in on their prey.
AB  - Herpesviruses subvert immune cell activation by inhibiting NK cell receptor
      (NKG2D)-activating ligands such as MICB. A human cytomegalovirus microRNA was
      recently shown to repress MICB expression. Nachmani et al. (2009) extend this
      finding to two other human herpesviruses, providing evidence for a conserved
      functional role of viral microRNAs despite no sequence conservation among them.

PMID- 19380111
TI  - Pathogenesis of flavivirus infections: using and abusing the host cell.
AB  - Flaviviruses, such as the dengue virus and the West Nile virus, are emerging
      arthropod-borne viruses that represent an immense global health problem.
      Considerable progress has been made in understanding flavivirus structure and
      replication strategies, but only now are the complex molecular interactions
      between the virus and host cell starting to be unraveled. In this Review, we
      discuss the ongoing efforts toward elucidating the molecular mechanisms that
      allow flaviviruses to manipulate host cell functions for successful infection. We
      draw attention to the importance of these studies in defining the pathogenesis of
      flaviviral diseases.

PMID- 19380112
TI  - The macrophage mannose receptor induces IL-17 in response to Candida albicans.
AB  - The cytokine IL-17 controls neutrophil-mediated inflammatory responses. The
      pattern recognition receptor(s) that induce Th17 responses during infection, in
      the absence of artificial mitogenic stimulation with anti-CD3/anti-CD28
      antibodies, remain obscure. We investigated the innate immune receptors and
      pathogen-associated molecular patterns involved in triggering Th17 responses
      during pathogen-specific host defense. The prototypic fungal pathogen Candida
      albicans was found to induce IL-17 more potently than Gram-negative bacteria.
      Candida mannan, but not zymosan, beta-glucans, Toll-like receptor (TLR) agonists,
      or the NOD2 ligand MDP, induced IL-17 production in the absence of anti-CD3/anti
      CD28 antibodies. Candida-induced IL-17 response was dependent on antigen
      presenting cells and the macrophage mannose receptor (MR), demonstrating that
      Candida mannan is not simply a mitogenic stimulus. The TLR2/dectin-1 pathway, but
      not TLR4 or NOD2, amplified MR-induced IL-17 production. This study identifies
      the specific pattern recognition receptors that trigger the Th17 response induced
      by a human pathogen in the absence of mitogenic stimulation.

PMID- 19380113
TI  - Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and
      a conserved p38 MAPK cascade.
AB  - Like other multicellular organisms, the model nematode C. elegans responds to
      infection by inducing the expression of defense genes. Among the genes
      upregulated in response to a natural fungal pathogen is nlp-29, encoding an
      antimicrobial peptide. In a screen for mutants that fail to express nlp-29
      following fungal infection, we isolated alleles of tpa-1, homologous to the
      mammalian protein kinase C (PKC) delta. Through epistasis analyses, we
      demonstrate that C. elegans PKC acts through the p38 MAPK pathway to regulate nlp
      29. This involves G protein signaling and specific C-type phospholipases acting
      upstream of PKCdelta. Unexpectedly and unlike in mammals, tpa-1 does not act via
      D-type protein kinases, but another C. elegans PKC gene, pkc-3, functions
      nonredundantly with tpa-1 to control nlp-29 expression. Finally, the tribbles
      like kinase nipi-3 acts upstream of PKCdelta in this antifungal immune signaling
      cascade. These findings greatly expand our understanding of the pathways involved
      in C. elegans innate immunity.

PMID- 19380114
TI  - Aldolase is essential for energy production and bridging adhesin-actin
      cytoskeletal interactions during parasite invasion of host cells.
AB  - Apicomplexan parasites rely on actin-based motility to drive host cell invasion.
      Prior in vitro studies implicated aldolase, a tetrameric glycolytic enzyme, in
      coupling actin filaments to the parasite's surface adhesin microneme protein 2
      (MIC2). Here, we test the essentiality of this interaction in host cell invasion.
      Based on in vitro studies and homology modeling, we generated a series of
      mutations in Toxoplasma gondii aldolase (TgALD1) that delineated MIC2 tail domain
      (MIC2t) binding function from its enzyme activity. We tested these mutants by
      complementing a conditional knockout of TgALD1. Mutations that affected
      glycolysis also reduced motility. Mutants only affecting binding to MIC2t had no
      motility phenotype, but were decreased in their efficiency of host cell invasion.
      Our studies demonstrate that aldolase is not only required for energy production
      but is also essential for efficient host cell invasion, based on its ability to
      bridge adhesin-cytoskeleton interactions in the parasite.

PMID- 19380115
TI  - Composition and three-dimensional architecture of the dengue virus replication
      and assembly sites.
AB  - Positive-strand RNA viruses are known to rearrange cellular membranes to
      facilitate viral genome replication. The biogenesis and three-dimensional
      organization of these membranes and the link between replication and virus
      assembly sites is not fully clear. Using electron microscopy, we find Dengue
      virus (DENV)-induced vesicles, convoluted membranes, and virus particles to be
      endoplasmic reticulum (ER)-derived, and we detect double-stranded RNA, a presumed
      marker of RNA replication, inside virus-induced vesicles. Electron tomography
      (ET) shows DENV-induced membrane structures to be part of one ER-derived network.
      Furthermore, ET reveals vesicle pores that could enable release of newly
      synthesized viral RNA and reveals budding of DENV particles on ER membranes
      directly apposed to vesicle pores. Thus, DENV modifies ER membrane structure to
      promote replication and efficient encapsidation of the genome into progeny virus.
      This architecture of DENV replication and assembly sites could explain the
      coordination of distinct steps of the flavivirus replication cycle.

PMID- 19380116
TI  - Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to
      escape recognition by natural killer cells.
AB  - Herpesviruses are known for their persistent lifelong latent infection, which is
      made possible by their vast repertoire of immune-evasion strategies. We have
      previously shown that a human cytomegalovirus (HCMV) microRNA represses
      expression of the stress-induced Natural Killer (NK) cell ligand, MICB, to escape
      recognition and consequent elimination by NK cells. Here, we show functional
      conservation among diverse microRNAs derived from different herpesviruses,
      including HCMV, Kaposi's sarcoma-associated herpesvirus (KSHV), and Epstein-Barr
      virus (EBV), in their ability to directly target MICB mRNA and reduce its
      expression. Although the various viral microRNAs share no sequence homology, they
      are functionally similar and target MICB at different yet adjacent sites during
      authentic viral infection. The finding that different herpesvirus microRNAs
      target MICB indicates that MICB plays a pivotal role in the clash between
      herpesviruses and humans.

PMID- 19380117
TI  - Clonal conditional mutagenesis in malaria parasites.
AB  - We describe here an efficient method for conditional gene inactivation in malaria
      parasites that uses the Flp/FRT site-specific recombination system of yeast. The
      method, developed in Plasmodium berghei, consists of inserting FRT sites in the
      chromosomal locus of interest in a parasite clone expressing the Flp recombinase
      via a developmental stage-specific promoter. Using promoters active in mosquito
      midgut sporozoites or salivary gland sporozoites to drive expression of Flp or
      its thermolabile variant, FlpL, we show that excision of the DNA flanked by FRT
      sites occurs efficiently at the stage of interest and at undetectable levels in
      prior stages. We applied this technique to conditionally silence MSP1, a gene
      essential for merozoite invasion of erythrocytes. Silencing MSP1 in sporozoites
      impaired subsequent merozoite formation in the liver. Therefore, MSP1 plays a
      dual role in the parasite life cycle, acting both in liver and erythrocytic
      parasite stages.

PMID- 19380118
TI  - Host cell interactome of tyrosine-phosphorylated bacterial proteins.
AB  - Selective interactions between tyrosine-phosphorylated proteins and their
      cognate, SH2-domain containing ligands play key roles in mammalian signal
      transduction. Several bacterial pathogens use secretion systems to inject
      tyrosine kinase substrates into host cells. Upon phosphorylation, these effector
      proteins recruit cellular binding partners to manipulate host cell functions. So
      far, only a few interaction partners have been identified. Here we report the
      results of a proteomic screen to systematically identify binding partners of all
      known tyrosine-phosphorylated bacterial effectors by high-resolution mass
      spectrometry. We identified 39 host interactions, all mediated by SH2 domains,
      including four of the five already known interaction partners. Individual
      phosphorylation sites recruited a surprisingly high number of cellular
      interaction partners suggesting that individual phosphorylation sites can
      interfere with multiple cellular signaling pathways. Collectively, our results
      indicate that tyrosine-phosphorylation sites of bacterial effector proteins have
      evolved as versatile interaction modules that can recruit a rich repertoire of
      cellular SH2 domains.

PMID- 19380119
TI  - The prognostic role of uterine artery Doppler studies in patients with late-onset
      preeclampsia.
AB  - OBJECTIVE: To evaluate the usefulness of uterine artery Doppler in the prediction
      of outcome in patients with late-onset preeclampsia. STUDY DESIGN: Patients with
      late-onset preeclampsia underwent Doppler interrogation of the uterine arteries.
      Patients with abnormal uterine artery Doppler were compared with those who had a
      normal uterine artery Doppler. RESULTS: Ninety-nine patients were included in the
      study group. Abnormal uterine artery Doppler group presented significantly lower
      gestational age at admission (36.1 +/- 2.1 weeks vs 37.2 +/- 1.9 weeks; P <
      .005), lower gestational age at delivery (36.5 +/- 1.9 weeks vs 37.7 +/- 1.7
      weeks; P < .005), lower birthweight (2429 +/- 590 g vs 3013 +/- 597 g; P <
      .0001), and a higher admission rate to neonatal intensive care unit (17/51 vs
      6/48; odds ratio, 3.5; 95% confidence interval, 1.2-9.5). No significant
      difference in the occurrence of maternal complications (10/51 vs 6/48; odds
      ratio, 1.7; 95% confidence interval, 0.5-4.9) was registered. CONCLUSION: Women
      with late-onset preeclampsia show a higher risk of perinatal complications if
      uterine resistance is increased although maternal outcome does not seem to be
      related to Doppler findings.

PMID- 19380120
TI  - Who is at risk for prolonged and postterm pregnancy?
AB  - OBJECTIVE: The objective of the study was to examine risk factors for postterm
      (gestational age >or= 42 weeks) or prolonged (gestational age >or= 41 weeks)
      pregnancy. STUDY DESIGN: We conducted a retrospective cohort study of all term,
      singleton pregnancies delivered at a mature, managed care organization. The
      primary outcome measures were the rates of pregnancies greater than 41 or 42
      weeks' gestation. Multivariable logistic regression models were used to control
      for potential confounding and interaction. RESULTS: Specific risk factors for
      pregnancy beyond 41 weeks of gestation include obesity (adjusted odds ratio
      [aOR], 1.26; 95% confidence interval [CI], 1.16-1.37), nulliparity (aOR, 1.46;
      95% CI 1.42-1.51), and maternal age 30-39 years (aOR, 1.06; 95% CI, 1.02-1.10)
      and 40 years or older (aOR, 1.07; 95% CI, 1.02-1.12). Additionally, African
      American, Latina, and Asian race/ethnicity were all associated with a lower risk
      of reaching 41 or 42 weeks of gestation. CONCLUSION: Our findings suggest that
      there may be biological differences that underlie the risk for women to progress
      to 41 or 42 weeks of gestation. In particular, obesity is a modifiable risk
      factor and could potentially be prevented with prepregnancy or interpregnancy
      interventions.

PMID- 19380121
TI  - Cost-effectiveness analysis of annual screening strategies for endometrial
      cancer.
AB  - OBJECTIVE: The objective of the study was to determine the cost-effectiveness of
      annual screening tests for endometrial cancer. STUDY DESIGN: Markov state
      transition model of the natural history of endometrial cancer used as the design
      for the study. Incidence was modeled for the general population and high risk
      groups (obese, body mass index [BMI] of >or= 30 kg/m(2); tamoxifen users).
      Strategies evaluated were no screening, annual endometrial biopsy, annual
      endovaginal ultrasound, and annual serum screening. Serum screening was based on
      a recently described biomarker panel (sensitivity of 0.98, specificity of 0.98).
      RESULTS: In the general population model, no screening was least expensive,
      whereas annual serum screening age at 50-75 years had incremental cost
      effectiveness ratio (ICER) of $60,363 per year of life saved (YLS) compared with
      no screening. In a high-risk population (obesity, BMI of >or= 30 kg/m(2)), annual
      serum screening at age 45-80 years had ICER of $41,226 per YLS compared with no
      screening. Annual endometrial biopsy and annual transvaginal ultrasound were
      dominated. CONCLUSION: Annual serum screening for endometrial cancer has the
      potential to be cost effective when applied to high-risk populations.

PMID- 19380122
TI  - Epidemiology and risk factors for early onset sepsis among very-low-birthweight
      infants.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence, causative
      pathogens, and risk factors for early onset sepsis (EOS) among very-low
      birthweight (VLBW) infants. STUDY DESIGN: This was a population based
      observational study. Data were prospectively collected by the Israel Neonatal
      Network between 1995 and 2005. Multivariable analyses identified independent risk
      factors for EOS. RESULTS: EOS developed in 383 of 15,839 infants (2.42%). Fifty
      five percent of pathogens isolated were gram-negative bacteria. Lack of prenatal
      care (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.32-2.86), delivery
      room resuscitation (OR, 2.49; 95% CI, 1.91-3.24), membrane rupture > 24 hours
      without amnionitis (OR, 2.10; 95% CI, 1.53-2.88), amnionitis with membrane
      rupture < 24 hours (OR, 4.28; 95% CI, 2.97-6.16), and amnionitis with membrane
      rupture >or= 24 hours (OR, 8.15; 95% CI, 5.98-11.10) were associated with EOS,
      but not antenatal steroids or gestational age. CONCLUSION: EOS was caused mainly
      by gram-negative bacteria. Prolonged rupture of membranes and amnionitis have an
      additive effect on EOS with an above 8-fold excess risk when both were present.

PMID- 19380123
TI  - Knowledge and attitudes regarding preconception care in a predominantly low
      income Mexican American population.
AB  - OBJECTIVE: The objective of the study was to determine knowledge and attitudes
      regarding preconception care in a low-income Mexican American population. STUDY
      DESIGN: This was a cross-sectional survey of 305 reproductive-age women at an
      urban public hospital. RESULTS: The sample was mostly Hispanic (88%) and pregnant
      (68%); 35% had not completed high school. Eighty-nine percent agreed that
      improving preconception health benefits pregnancy. Seventy-seven percent
      expressed some interest in preconception health care with the obstetrics
      gynecology office at the preferred location. The average knowledge of
      preconception care score was 76% (higher score more favorable). Areas of higher
      knowledge included the effects on pregnancy of folic acid; alcohol use; substance
      use; and verbal, physical, and sexual abuse; lower knowledge was found for the
      effects of cat litter and fish products. CONCLUSION: There was interest in
      preconception education and agreement that preconception health has a positive
      effect on pregnancy. Fewer respondents agreed that it had a good effect than a
      suburban sample in the same region (89% vs 98%).

PMID- 19380124
TI  - A randomized controlled trial of cervical scanning vs history to determine
      cerclage in women at high risk of preterm birth (CIRCLE trial).
AB  - OBJECTIVE: We sought to compare history-indicated placement of cervical cerclage
      based on history- vs ultrasound-indicated placement in women at risk of preterm
      birth. STUDY DESIGN: We conducted a randomized controlled trial of history
      indicated cervical cerclage suture based on history (clinician preference) vs
      ultrasound (< 20 mm cervical length) indicated in women at increased risk.
      RESULTS: The incidence of the primary outcome, preterm delivery between 24(+0)
      and 33(+6) weeks, was similar: 19/125 (15%) in the history-indicated group vs
      18/122 (15%) in the ultrasound-indicated group (relative risk [RR], 0.97; 95%
      confidence interval [CI], 0.54-1.76). Those women randomized to the ultrasound
      indicated arm were significantly more likely to receive a cerclage (32% vs 19%;
      RR, 1.66; 95% CI, 1.07-2.47) and progesterone (39% vs 25%; RR, 1.55; 95% CI, 1.06
      2.25). CONCLUSION: Screening women at high risk with cervical ultrasound to
      determine cerclage placement results in more intervention but similar outcome
      compared with history-indicated placement.

PMID- 19380125
TI  - EEG-based classification for elbow versus shoulder torque intentions involving
      stroke subjects.
AB  - The ultimate aim for classifying elbow versus shoulder torque intentions is to
      develop robust brain-computer interface (BCI) devices for patients who suffer
      from movement disorders following brain injury such as stroke. In this paper, we
      investigate the advanced classification approach classifier-enhanced time
      frequency synthesized spatial pattern algorithm (classifier-enhanced TFSP) in
      classifying a subject's intent of generating an isometric shoulder abduction
      (SABD) or elbow flexion (EF) torque using signals obtained from 163 scalp
      electroencephalographic (EEG) electrodes. Two classifiers, the support vector
      classifier (SVC) and the classification and regression tree (CART), are
      integrated in the TFSP algorithm that decomposes the signal into a weighted time,
      frequency and spatial feature space. The resulting high-performing methods (SVC
      TFSP and CART-TFSP) are then applied to experimental data collected in four
      healthy subjects and two stroke subjects. Results are compared with the original
      TFSP, and significantly higher reliability in both healthy subjects (92% averaged
      over four healthy subjects) and stroke subjects (75% averaged over two subjects)
      are achieved. The accuracies of classifier-enhanced TFSP methods are further
      improved after a rejection scheme is applied (approximately 100% in healthy
      subjects and >80% in stroke subjects). The results are among the highest
      reliability reported in literature for tasks with spatial representations on the
      motor cortex as close as shoulder and elbow. The paper also discusses the impact
      of applying rejection strategy in detail and reports the existence of an optimal
      rejection rate on a stroke subject. The results indicate that the proposed
      algorithms are promising for future use of rehabilitative BCI applications in
      neurologically impaired patients.

PMID- 19380126
TI  - The exponential decay characteristic of the spectral distribution of blood
      pressure wave in radial artery.
AB  - This study analyzed the exponential decay characteristic of the harmonic peaks in
      the spectrum of blood pressure wave (BPW) from radial artery at wrist. Low-order
      harmonic deviation (LHD), high-order harmonic deviation (HHD), total harmonic
      deviation (THD) and exponent (alpha) were developed to assess the exponential
      decay feature of normal subjects (N group) and the patients with palpitation (P
      group). The statistical results indicate that only the HHD (p value=0.01<0.05) of
      N group is significantly less than that of P group while LHD (p value=0.08>0.05),
      THD (p value=0.22>0.05) and alpha (p value=0.23>0.05) make no significant
      differences. The results imply that the spectral harmonic peaks for patient
      subjects exhibit more severe deviations in high-order harmonics along the
      exponential decay curve than those for normal subjects. In conclusion, this paper
      proposes a novel viewpoint to observe how the heart distributes blood into
      arterial system under normal and abnormal situations in spectral domain.

PMID- 19380127
TI  - Clomiphene citrate-induced severe hypertriglyceridemia.
AB  - OBJECTIVE: To report a case of severe hypertriglyceridemia associated with
      clomiphene citrate (CC) treatment. DESIGN: Case report. SETTING: A patient
      referred to an endocrinology clinic of a state hospital. PATIENT(S): A 29-year
      old, overweight woman with a history of polycystic ovary syndrome who had been
      given clomiphene citrate (CC) for ovulation induction and presented with severe
      hypertriglyceridemia. She had a family history of type 2 diabetes and
      hyperlipidemia. INTERVENTION(S): Clomiphene citrate treatment was discontinued,
      and gemfibrozil treatment at a dose of 1,200 mg/d was started. MAIN OUTCOME
      MEASURE(S): Serum lipid levels. RESULT(S): With the discontinuation of CC
      treatment and start of a specific lipid-lowering agent, the patient's lipid
      profile improved. After 3 months, CC therapy was restarted, and again severe
      hypertriglyceridemia developed, which resolved with the previous treatment
      strategies. CONCLUSION(S): Clomiphene citrate should be used cautiously in women
      having risk factors for dyslipidemia, and, even in the presence of a normal lipid
      profile, lipid levels should be closely monitored when CC treatment is
      instituted.

PMID- 19380128
TI  - Splitting plaster with a scalpel blade: a safe way to allow easy splitting of a
      plaster [Injury 2008;39 (3):368-70].

PMID- 19380129
TI  - Platelet-rich plasma: new clinical application: a pilot study for treatment of
      jumper's knee.
AB  - This study describes a simple, low-cost, minimally invasive way to apply PRP
      growth factors to chronic patellar tendinosis; 20 male athletes with a mean
      history of 20.7 months of pain received treatment, and outcomes were
      prospectively evaluated at 6 months follow-up. No severe adverse events were
      observed, and statistically significant improvements in all scores were recorded.
      The results suggest that this method may be safely used for the treatment of
      jumper's knee, by aiding the regeneration of tissue which otherwise has low
      healing potential.

PMID- 19380130
TI  - Stabilisation of articular fractures of the distal humerus: early experience with
      a novel perpendicular plate system.
AB  - INTRODUCTION: The treatment of fractures of the distal humerus is difficult and
      involves the risk of bad functional results, particularly with articular
      fractures or impaired bone quality. Anatomical reconstruction and stable fixation
      allowing early mobilisation of the elbow are the basic prerequisites for good
      clinical outcomes. The aim of our study was to evaluate whether the Distal
      Humerus Plate (DHP, Synthes), a novel, perpendicular, fixed-angle plate system,
      fulfils the requirements for this treatment goal. METHODS: From 2004 to 2007, 46
      consecutive patients (19 men and 21 women; mean age of 60.5 years) underwent open
      reduction and internal fixation with the new DHP system. Six patients were lost
      to follow up. The remaining 40 patients were followed up for 11 months (range 4
      24 months). Follow up involved assessment of functional outcome using the Mayo
      Elbow Performance Score (MEPS) and Liverpool Elbow Score (LES), reduction results
      and complication rates. Subgroup analyses involved comparisons of younger (<60
      years) to elderly (> or =60 years) patients and type C3 injuries versus other
      fracture patterns. RESULTS: Only six cases received primary internal fixation,
      whilst 31 patients were temporarily stabilised by either external fixation or
      cast before ORIF could be performed. Three patients were treated for implant
      failure (systems other than DHP) after surgery in other hospitals. The mean time
      from injury to internal fixation was 7 days. Open fractures were present in 10
      cases. Olecranon osteotomy was required for reduction in 35 cases. Mean operation
      time was 215 min. 'Good' or 'excellent' results were observed in 29/40 patients.
      Median MEPS and LES were 84 and 8.1 points, respectively. Mean ROM was 100
      degrees. We found no significant differences in the subgroup analyses; however,
      there was a tendency towards better functional results in younger patients and
      injuries without comminution of the articular surface. Complications comprised
      two superficial wound infections, two cases of heterotopic ossification, one case
      of delayed union and five cases of transient ulnar neuropathy. Implant failure
      was observed twice in one patient. CONCLUSION: Open reduction and internal
      fixation with the DHP system provides reliable, stable fixation allowing early
      functional mobilisation of the elbow joint, even in complex fractures and
      impaired bone quality, resulting in good outcomes for the majority of patients.
      The complication rate reported here is comparable to that of other implants, but
      the low number of implant failures is promising and warrants further
      investigation.

PMID- 19380131
TI  - Use of the trauma pelvic orthotic device (T-POD) for provisional stabilisation of
      anterior-posterior compression type pelvic fractures: a cadaveric study [Injury,
      Int J Care Injured 2008;39:903-6].

PMID- 19380132
TI  - The percutaneous antegrade scaphoid fracture fixation--a safe method?
AB  - INTRODUCTION: The object of this study was to assess the risk of injury to
      tendons, nerves and vessels in percutaneous antegrade scaphoid fracture fixation.
      METHODS: Forty cadaveric forearms were used in this study. A guide wire for
      cannulated headless compression screws was inserted percutaneously in each
      scaphoid according to established surgical technique. RESULTS: No nerve or vessel
      injuries were observed. Tendons however were injured in 5 out of the 40
      specimens. This included the extensor pollicis longus tendon in two specimens,
      the extensor carpi radialis tendon in two specimens and the extensor digitorum
      tendon in one specimen. CONCLUSIONS: Soft tissue injuries may be avoided by
      extending the skin incision and performing blunt dissection down to guide wire
      and screw entry point. In this manner, dorsal antegrade fixation of scaphoid
      fractures by using cannulated headless compression screws can be considered to be
      a safe and reliable technique for fixation of scaphoid fractures.

PMID- 19380133
TI  - Significant impact of chromosomal locus 1p13.3 on serum LDL cholesterol and on
      angiographically characterized coronary atherosclerosis.
AB  - OBJECTIVES: Recently, a significant impact of a new locus on chromosome 1p13.3 on
      serum LDL (low-density lipoprotein) cholesterol and clinical events of coronary
      artery disease (CAD) was described. Potential associations between variants on
      this locus and angiographically characterized coronary atherosclerosis are
      unknown. We therefore aimed at investigating the association of variants of locus
      1p13.3 with coronary atherosclerosis. METHODS: We performed genotyping of
      variants rs599839, rs646776, and rs4970834 on chromosome 1p13.3 in a large cohort
      of 1610 consecutive Caucasian patients undergoing coronary angiography, where
      lesions of 50% or more were classified as significant. RESULTS: Compared to the
      homozygous common allele the rare alleles of variants rs599839, rs646776, and
      rs4970834 were significantly associated with decreased serum LDL cholesterol
      (132+/-40mg/dl vs. 125+/-36mg/dl, P=0.003, 132+/-40mg/dl vs. 124+/-36mg/dl,
      P<0.001, and 131+/-40mg/dl vs. 125+/-37mg/dl, P=0.005, respectively). Further,
      carriers of the rare alleles of variants rs599839 and rs646776 were at a
      significantly lower risk of significant coronary stenoses than subjects who were
      homozygous for the frequent alleles, with odds ratios (ORs) of 0.78 [0.63-0.96];
      P=0.019 and 0.74 [0.60-0.91]; P=0.004, respectively. After multivariate
      adjustment including LDL cholesterol, the protective effect of the rare allele of
      variant rs646776, but not of variant rs599839, on CAD risk remained significant
      (OR=0.77 [0.61-0.98], P=0.034). CONCLUSIONS: We conclude that chromosomal locus
      1p13.3 is significantly associated with both, serum LDL cholesterol and coronary
      atherosclerotic lesions.

PMID- 19380134
TI  - Intracoronary versus intravenous abciximab administration in patients with ST
      elevation myocardial infarction undergoing thrombus aspiration during primary
      percutaneous coronary intervention--effects on soluble CD40 ligand
      concentrations.
AB  - INTRODUCTION: CD40 ligand has been suggested to play a pathogenic role in
      atherogenesis and coronary artery disease progression. Clinical studies suggest
      that intravenous (IV) abciximab administration attenuates the acute inflammatory
      response associated with percutaneous coronary intervention (PCI). The anti
      inflammatory effects of intracoronary (IC) versus IV administration of abciximab
      have not been systematically investigated. We assessed changes in soluble CD40
      ligand (sCD40L) concentrations in response to IC versus IV abciximab in patients
      with ST-elevation myocardial infarction (STEMI) undergoing thrombus-aspirating
      device during primary PCI. METHODS: Patients were randomized to receive IC (n=25)
      or IV (n=25) bolus abciximab followed in every case by a 12-h IV abciximab
      infusion. sCD40L was measured immediately before the administration of abciximab
      (baseline) and 60min post bolus administration. RESULTS: Clinical baseline and
      angiographic characteristics were similar in both patient groups. Similarly,
      there were no significant differences in baseline serum sCD40L levels in the IC
      group compared to IV group (116.6+/-42.13pg/mL vs 124.9+/-43.04pg/mL, P=0.49). At
      60min post PCI, however, sCD40L levels decreased by 23% (P<0.001) in the IC group
      and by 11% (P<0.001) in the IV group. sCD40L levels 60min post PCI were
      significantly reduced, particularly in the IC group compared to the IV group
      (73.04+/-12.21pg/mL vs 99.92+/-25.89pg/mL, P<0.001). CONCLUSION: In STEMI
      patients undergoing primary PCI, IC bolus administration of abciximab was
      associated with a larger reduction in sCD40L levels compared to standard IV
      bolus. Whether this more powerful anti-inflammatory effect of IC abciximab
      translates into improved clinical outcomes deserves investigation.

PMID- 19380135
TI  - Mannose binding lectin deficiency and triglyceride-rich lipoprotein metabolism in
      normolipidemic subjects.
AB  - Mannose binding lectin (MBL) is one of the three initiators of complement
      activation and is therefore closely linked to inflammation. MBL deficiency has
      been associated with the generation of atherosclerosis. Since atherosclerosis,
      the complement system and postprandial lipemia are linked to inflammation, we
      studied postprandial lipoprotein metabolism in MBL deficiency. An observational
      study was carried out in 107 volunteers (21% MBL deficient). Classical
      cardiovascular risk factors were not different between subjects with and without
      MBL deficiency. Oral fat loading tests in 8 MBL deficient and 14 MBL sufficient
      subjects showed similar postprandial triglyceride, free fatty acid,
      hydroxybutyric acid and complement component 3 concentrations. MBL deficient
      subjects had 2.4 times lower postprandial Sf>400 (chylomicron)-apoB48
      concentrations, but in contrast a 2-3.5 times increased Sf 60-400 (VLDL1-TG) and
      Sf 60-400-apoB100 response. MBL activity was inversely related to the
      postprandial Sf 60-400-TG increase. Despite lower postprandial Sf>400-apoB48
      concentrations, MBL deficient subjects show an accumulation of Sf 60-400
      lipoproteins.

PMID- 19380137
TI  - An investigation of the effect of conformity of knee hemiarthroplasty designs on
      contact stress, friction and degeneration of articular cartilage: a tribological
      study.
AB  - Hemiarthroplasty is a potentially attractive alternative to knee replacement for
      young, active patients, as it allows preservation of more bone stock for
      potential revisions. However, there has been limited success with
      hemiarthroplasty or spacers to date. The wear and degradation of the biomaterial
      cartilage interface is of paramount importance in the design and success of
      hemiarthroplasties. A comprehensive understanding of the tribological performance
      of hemiarthroplasty implants in the natural joint is required. The objective of
      this study was to investigate the tribological response of bovine medial
      compartmental knees, both natural and hemiarthroplasty replaced, under
      physiological loads and motion. The conformity of these metallic
      hemiarthroplasties was varied (conforming plates with radius of 50 mm and radius
      of 100 mm and a flat plate design), in order to examine the effects of conformity
      and contact stress, on the friction, friction shear stress and cartilage
      degeneration. With decreasing conformity of hemiarthroplasty bearings, an
      increase in contact stress was found, which resulted in elevated friction,
      elevated friction shear stress and increased cartilage degeneration. A strong
      correlation was found between contact stress and wear and between friction shear
      stress and wear. This new and unique in vitro tribological simulation has shown
      the direct elevation of friction, surface fibrillation and biomechanical wear of
      cartilage, upon replacing the tibia with a hemiarthroplasty, particularly when
      using low conformity hemiarthroplasty designs.

PMID- 19380136
TI  - Physical inactivity interacts with an endothelial lipase polymorphism to modulate
      high density lipoprotein cholesterol in the GOLDN study.
AB  - BACKGROUND: Plasma high density lipoprotein (HDL) cholesterol (HDL-C)
      concentration is highly heritable but is also modifiable by environmental factors
      including physical activity. HDL-C response to exercise varies among individuals,
      and this variability may be associated with genetic polymorphisms in the key
      regulators of HDL metabolism including endothelial lipase (LIPG). METHODS: We
      examined associations between variants LIPG T111I (rs2000813) and LIPG i24582
      (rs6507931), HDL and television viewing/computer use ("screen time") as a marker
      for physical inactivity in a population with high prevalence of metabolic
      syndrome. Subjects consisted of 539 White men and 584 women (mean+/-S.D., 49+/-16
      years) participating in the GOLDN study. RESULTS: We did not observe an
      association with either LIPG SNP or HDL independently of screen time. In multi
      adjusted linear regression models, HDL interacted significantly with screen time
      as a continuous variable in LIPG i24582 subjects with TT genotype (P<0.05). By
      dichotomizing screen time into high and low levels, we found significant genotype
      associated differences in HDL in women but not men. When screen time was
      >or=2.6h/day, the concentrations of total HDL-C, large HDL, large low density
      lipoprotein (LDL) were lower, the concentration of small LDL was higher and HDL
      and LDL particle sizes were smaller in subjects with LIPG i24582 TT compared to
      CT and CC subjects (P<0.05). CONCLUSIONS: We found a significant gene-physical
      inactivity interaction for HDL and some LDL measures for the LIPG i24582
      polymorphism. Higher levels of physical activity may be protective for HDL-C
      concentrations and low activity detrimental in LIPG i24582 TT individuals,
      especially in women.

PMID- 19380138
TI  - Kinematics and kinetics of unanticipated misstep conditions: femoral fracture
      implications in the elderly.
AB  - Most hip fractures are thought to occur after falling during everyday activities.
      We speculated that hip fractures might also occur because of excessive loading of
      the hip joint during an unexpected misstep consequently leading to a fall. The
      aims of this study were to explore the kinematics and kinetics of the lower
      extremity joints during missteps as compared with regular stepping, as well as to
      compare the magnitude of forces acting upon the hip joint with the threshold
      forces expected to fracture the hip. Fourteen healthy adults performed two
      forward steps on a 17.8 cm high platform under the following four conditions:
      forward with and without vision, as well as a misstep (the box for the final step
      unexpectedly removed without participant awareness), and regular stepping down
      with eyes open. The results revealed no differences between stepping forward with
      and without vision. When compared with both stepping forward and regular stepping
      down, the misstep revealed altered joint positions accompanied by increased
      forces and moments acting upon the hip joint. For example, the peak vertical
      proximal thigh segment force was 3.05+/-0.55 BW vs. 1.23+/-0.14 BW and 0.91+/
      0.09 BW (p<.001; misstep vs. regular stepping down and stepping forward,
      respectively), while the proximal thigh segment moment in frontal plane was
      1.39+/-0.70 Nm/kg vs. 0.18+/-0.32 Nm/kg of adduction and 0.16+/-0.19 Nm/kg of
      abduction (p<.001). When compared with the literature data, the forces during
      misstep were within the range of those forces that could result in hip fractures
      in the elderly. Therefore, it may be possible for the elderly to experience
      hip/proximal femur fractures during missteps prior to falling.

PMID- 19380139
TI  - Prediction of bone density around orthopedic implants delivering bisphosphonate.
AB  - The fixation of an orthopedic implant depends strongly upon its initial
      stability. Peri-implant bone may resorb shortly after the surgery. This
      resorption is directly followed by new bone formation and implants fixation
      strengthening, the so-called secondary fixation. If the initial stability is not
      reached, the resorption continues and the implant fixation weakens, which leads
      to implant loosening. Studies with rats and dogs have shown that a solution to
      prevent peri-implant resorption is to deliver bisphosphonate from the implant
      surface. The aims of the study were, first, to develop a model of bone remodeling
      around an implant delivering bisphosphonate, second, to predict the
      bisphosphonate dose that would induce the maximal peri-implant bone density, and
      third to verify in vivo that peri-implant bone density is maximal with the
      calculated dose. The model consists of a bone remodeling equation and a drug
      diffusion equation. The change in bone density is driven by a mechanical stimulus
      and a drug stimulus. The drug stimulus function and the other numerical
      parameters were identified from experimental data. The model predicted that a
      dose of 0.3 microg of zoledronate on the implant would induce a maximal bone
      density. Implants with 0.3 microg of zoledronate were then implanted in rat
      femurs for 3, 6 and 9 weeks. We measured that peri-implant bone density was 4%
      greater with the calculated dose compared to the dose empirically described as
      best. The approach presented in this paper could be used in the design and
      analysis processes of experiments in local delivery of drug such as
      bisphosphonate.

PMID- 19380140
TI  - Comparison of different state space definitions for local dynamic stability
      analyses.
AB  - Measures of local dynamic stability, such as the local divergence exponent
      (lambda*(s)) quantify how quickly small perturbations deviate from an attractor
      that defines the motion. When the governing equations of motion are unknown, an
      attractor can be reconstructed by defining an appropriate state space. However,
      state space definitions are not unique and accepted methods for defining state
      spaces have not been established for biomechanical studies. This study first
      determined how different state space definitions affected lambda*(s) for the
      Lorenz attractor, since exact theoretical values were known a priori. Values of
      lambda*(s) exhibited errors <10% for 7 of the 9 state spaces tested. State spaces
      containing redundant information performed the poorest. To examine these effects
      in a biomechanical context, 20 healthy subjects performed a repetitive sawing
      like task for 5 min before and after fatigue. Local stability of pre- and post
      fatigue shoulder movements was compared for 6 different state space definitions.
      Here, lambda*(s)decreased post-fatigue for all 6 state spaces. Differences were
      statistically significant for 3 of these state spaces. For state spaces defined
      using delay embedding, increasing the embedding dimension decreased lambda*(s) in
      both the Lorenz and experimental data. Overall, our findings suggest that direct
      numerical comparisons between studies that use different state space definitions
      should be made with caution. However, trends across experimental comparisons
      appear to persist. Biomechanical state spaces constructed using positions and
      velocities, or delay reconstruction of individual states, are likely to provide
      consistent results.

PMID- 19380141
TI  - Tensile and shear properties of fingernails as a function of a changing humidity
      environment.
AB  - The mechanical properties of fingernails are important because of their impact in
      preventing damage and in maintaining their appearance. In particular, knowing the
      effect of local environmental conditions can tell us how they might best be
      protected. In order to better understand this, tensile tests were carried out to
      characterise the properties of fingernails at different relative humidities.
      Cyclic tests were also conducted to investigate the ability of the structure to
      recover deformation at different moisture contents. Torsional tests were
      performed to determine the shear modulus of the keratinous matrix material which
      binds together the fibrous components of the fingernails. This enabled an
      analysis of how the material may resist bending, torsion and permanent
      deformation in a natural environment. In particular, it is shown that at low
      relative humidity the nails are more brittle, and at high moisture contents they
      are more flexible. Increasing relative humidity lowers torsional stiffness much
      more than tensile stiffness, suggesting that moisture plasticises the matrix
      rather than affecting the fibres. The twist to bend ratio is minimised at 55% RH,
      close to the natural condition of nails which should minimise susceptibility to
      torsional damage due to plasticisation and a disruption of the matrix material
      binding the keratin fibres.

PMID- 19380143
TI  - Repeated application of incremental landing impact loads to intact knee joints
      induces anterior cruciate ligament failure and tibiofemoral cartilage deformation
      and damage: A preliminary cadaveric investigation.
AB  - Anterior cruciate ligament (ACL) injury is a major problem worldwide and prevails
      during high-impact activities. It is not well-understood how the extent and
      distribution of cartilage damage will arise from repetitive landing impact loads
      that can lead to ACL failure. This study seeks to investigate the sole effect of
      repetitive incremental landing impact loads on the induction of ACL failure, and
      extent and distribution of tibiofemoral cartilage damage in cadaveric knees. Five
      cadaveric knees were mounted onto a material testing system at 70 degrees flexion
      to simulate landing posture. A motion-capture system was used to track rotational
      and translational motions of the tibia and femur, respectively. Each specimen was
      compressed at a single 10Hz haversine to simulate landing impact. The compression
      trial was successively repeated with increasing actuator displacement till a
      significant compressive force drop was observed. All specimens underwent ACL
      failure, which was confirmed via magnetic resonance scans and dissection. Volume
      analysis, thickness measurement and histological techniques were employed to
      assess cartilage lesion status. For each specimen, the highest peak compressive
      force (1.9-7.8kN) was at the final trial in which ACL failure occurred;
      corresponding posterior femoral displacement (7.6-18.0mm) and internal tibial
      rotation (0.6 degrees -4.7 degrees ) were observed. Significant compressive force
      drop (79.8-90.9%) was noted upon ACL failure. Considerable cartilage deformation
      and damage were found in exterior, posterior and interior femoral regions with
      substantial volume reduction in lateral compartments. Repeated application of
      incremental landing impact loads can induce both ACL failure and cartilage
      damage, which may accelerate the risk of developing osteoarthritis.

PMID- 19380142
TI  - Relationship between nutrition factors and osteopenia: Effects of experimental
      diets on immature bone quality.
AB  - To investigate the influence of experimental diets on morphological and
      mechanical characteristics of immature bone, this study thoroughly examined the
      nutrition-bone connection. A non-destructive evaluation method involving high
      resolution in-vivo micro-computed tomography and finite element (FE) analysis was
      used to investigate the relationship between obesity and osteopenia-two disorders
      of body composition. Correlation of nutritional deficiency with bone
      characteristics was also investigated. Some recent studies have shown that both
      obesity and osteopenia share several common genetic and environmental factors.
      However, there have been few studies correlating these pathologies in-vivo from a
      structural and biomechanical point of view. In the present study, detailed
      changes in morphological and mechanical characteristics of trabecular bone
      architecture were detected and tracked by longitudinal studies of morphometric
      parameters and simulated compression testing. Rats were randomized into three
      groups: overeaten diet (OD) for formation of obesity, normal diet (ND), and
      restricted diet (RD) in which rats received 65% of the normal diet. In the OD and
      ND groups, all structural parameters changed significantly (p<0.05). The degree
      of alteration in the structural parameters of the ND group was similar to that of
      the RD group (p<0.05). In simulated compression tests using FE models, the
      effective modulus of the OD group significantly decreased, depending on measuring
      time (p<0.05), whereas that of the ND and RD groups significantly increased
      (p>0.05). The key finding of the present study is that fat mass is
      morphologically and mechanically inversely correlated with bone mass when the
      mechanical loading effects of greater body weight on bone mass are applied.

PMID- 19380144
TI  - Estimating uncertainty in analytical procedures based on chromatographic
      techniques.
AB  - Chromatographic techniques are very frequently used in analytical procedures for
      the separation, determination and identification of a wide spectrum of analytes
      present in samples with complex and sometimes variable matrices. However, the
      estimation of uncertainty of the final results does not include the uncertainties
      associated with the actual chromatographic process. In effect, such results
      cannot always be treated as a reliable source of analytical information. In this
      paper we present the basic terms, sources of uncertainty, and methods of
      calculating the combined uncertainty that any presentation of final
      determinations should include.

PMID- 19380145
TI  - One-step synthesis to photoelectric hybrid composite of N-vinylcarbazole-methyl
      acrylate copolymer and ZnO nanocrystals via nanocrystals-initiated
      polymerization.
AB  - This study designs a polymerization, in which ZnO colloids are used to initiate a
      copolymerization of N-vinylcarbazole and methyl acrylate, to synthesize
      functional composites for fabricating photoelectric devices. It is proved that a
      block copolymer is synthesized and a nanocomposite consisting of the ZnO and
      copolymer is obtained simultaneously. As a result, the ZnO nanocrystals are
      finely dispersed in the polymer matrix. A film-device is prepared from the
      obtained nanocomposite which has good film-forming ability and measured about
      photocurrents under illumination.

PMID- 19380146
TI  - Facile synthesis of polyaniline "sunflowers" with arrays of oriented nanorods.
AB  - Polyaniline (PANI) "sunflowers" made of arrays of oriented nanorods were
      synthesized by chemical oxidative polymerization of aniline in the presence of
      cetyltrimethylammonium bromide (CTAB) and suitable concentration of HNO3 at about
      0 degrees C (ice bath). The reaction conditions, such as the concentration of
      reagents and reaction temperature were systematically investigated and controlled
      on the preparation of PANI "sunflowers". The results also suggest that HNO3
      probably plays a key role in forming PANI "sunflowers". A possible forming
      mechanism of the PANI nanostructures is offered.

PMID- 19380147
TI  - A cauliflower-like gold structure for superhydrophobicity.
AB  - We present a two-step route to produce a hierarchical cauliflower-like gold
      structure that involves the adsorption of gold nanoparticles described by the
      random sequential adsorption (RSA) model, followed by the electrochemical growth
      on the surfaces of the primary gold nanoparicles. The structure was confirmed
      using scanning electron microscopy (SEM), energy dispersive spectrometer analysis
      (EDS), and X-ray diffraction (XRD). After fluoroalkylsilane modification, the
      cauliflower-like structured surface exhibits a high contact angle and a low
      sliding angle.

PMID- 19380148
TI  - Ripening of a draining foam bubble.
AB  - A forced Ostwald ripening experiment is performed on a single foam bubble. The
      bubble size is followed as the system is wetted with a constant liquid flow rate
      delivered from one of the bubble Plateau borders. Obtained ripening velocities
      cannot be described with a model based on a constant film thickness assumption.
      Within these well-controlled experimental conditions, the film thickness is
      measured and found to depend on the imposed liquid flow rate. It is shown that
      the bubble growth rate is well predicted as the films thickness evolution is
      explicitly introduced in the ripening model. Finally, it is suggested that
      existing results for the coarsening of draining foams could be understood
      following the approach validated on the bubble scale.

PMID- 19380149
TI  - Effect of surfactant surface coverage on formation of solid lipid nanoparticles
      (SLN).
AB  - The effect of surfactant surface coverage on formation and stability of Tween 20
      stabilized tripalmitin solid lipid nanoparticles (SLN) was investigated. A lipid
      phase (10% w/w tripalmitin) and an aqueous phase (2% w/w Tween 20, 10 mM
      phosphate buffer, pH 7) were heated to 75 degrees C and then homogenized using a
      microfluidizer. The resulting oil-in-water emulsion was kept at a temperature (37
      degrees C) above the crystallization temperature of the tripalmitin to prevent
      solidification of emulsion droplets, and additional surfactant at various
      concentrations (0-5% w/w Tween 20) was added. Droplets were then cooled to 5
      degrees C to initiate crystallization and stored at 20 degrees C for 24 h.
      Particle size and/or aggregation were examined visually and by light scattering,
      and crystallization behavior was examined by differential scanning calorimetry
      (DSC). Excess Tween 20 concentration remaining in the aqueous phase was measured
      by surface tensiometry. Emulsion droplets after homogenization had a mean
      particle diameter of 134.1+/-2.0 nm and a polydispersity index of 0.08+/-0.01.
      After cooling to 5 degrees C at low Tween 20 concentrations, SLN dispersions
      rapidly gelled due to aggregation of particles driven by hydrophobic attraction
      between insufficiently covered lipid crystal surfaces. Upon addition of 1-5% w/w
      Tween 20, SLN dispersions became increasingly stable. At low added Tween 20
      concentration (<1% w/w) the SLN formed gels but only increased slightly at higher
      surfactant concentrations (>1% w/w). The Tween 20 concentration in the aqueous
      phase decreased after tripalmitin crystallization suggesting additional
      surfactant adsorption onto solid surfaces. At higher Tween 20 concentrations, SLN
      had increasingly complex crystal structures as evidenced by the appearance of
      additional thermal transition peaks in the DSC. The results suggest that
      surfactant coverage at the interface may influence crystal structure and
      stability of solid lipid nanoparticles via surface-mediated crystal growth.

PMID- 19380151
TI  - Speech perception deficits by Chinese children with phonological dyslexia.
AB  - Findings concerning the relation between dyslexia and speech perception deficits
      are inconsistent in the literature. This study examined the relation in Chinese
      children using a more homogeneous sample-children with phonological dyslexia. Two
      experimental tasks were administered to a group of Chinese children with
      phonological dyslexia, a group of age-matched control children, and a group of
      adults. In addition to a categorical perception task, a selective adaptation task
      was carried out. The results indicated that Chinese children with phonological
      dyslexia were less consistent than both the child and adult control groups in
      identifying stimuli within a given phonetic category. Furthermore, they did not
      show any significant adaptation effects in the selective adaptation task even
      when the adapting stimulus was identical to an endpoint stimulus in the test
      continuum. It seems that children with phonological dyslexia have a general
      deficiency in representing and processing speech stimuli.

PMID- 19380152
TI  - Levels of the potential biomarker p11 in peripheral blood cells distinguish
      patients with PTSD from those with other major psychiatric disorders.
AB  - Posttraumatic stress disorder (PTSD) is a severely debilitating anxiety disorder.
      Over 80% of patients with PTSD also exhibit other psychiatric condition, such as
      bipolar disorder (BP) or major depression (MDD). Previously, it has been found
      that p11 mRNA expression was significantly changed in post mortem cortex of
      patients with PTSD and depression. We hypothesize that p11 mRNA levels in the
      peripheral blood cells will be a potential biomarker for PTSD with heterogeneity
      in terms of type of trauma, time since trauma and duration of illness. We
      examined the peripheral blood mononuclear cell (PBMC) P11 mRNA of patients with
      PTSD (n=13), major depressive disorder (MDD, n=16), bipolar disorder (BP, n=24),
      and schizophrenia (SCZ, n=12) or controls (n=14) using quantitative real-time PCR
      and the circulating levels of cortisol in blood plasma and saliva of PTSD using
      radioimmunoassay kit CORT-CT2. The Hamilton Rating Scale for Depression (HAMD)
      and Anxiety (HARS), the Chinese version of the Davidson Trauma Scale-Frequency
      (CDTS-F) and the Chinese version of the Davidson Trauma Scale-Severity (CDTS-S),
      and Impact of Event Scale-Revised (IES-R) were administered. We found that
      patients with PTSD had lower levels of p11 mRNA than control subjects, while
      those with MDD, BP and SCZ had significantly higher p11 levels than the controls.
      P11 mRNA levels were positively correlated with the scores of HAMD (r=0.62,
      p<0.05), CDTS-F (r=0.71, p<0.05) and CDTS-S (r=0.62, p<0.05), while they did not
      correlate with scores of HARS and IES-R. Basal levels of plasma and salivary
      cortisol of PTSD patients were not statistically different from those of
      controls. Our findings suggest that PBMC p11 mRNA expression levels may serve as
      a potential biomarker to distinguish PTSD from BP, MDD and SCZ.

PMID- 19380150
TI  - Cortical development, plasticity and re-organization in children with cochlear
      implants.
AB  - A basic tenet of developmental neurobiology is that certain areas of the cortex
      will re-organize, if appropriate stimulation is withheld for long periods.
      Stimulation must be delivered to a sensory system within a narrow window of time
      (a sensitive period) if that system is to develop normally. In this article, we
      will describe age cut-offs for a sensitive period for central auditory
      development in children who receive cochlear implants. We will review de-coupling
      and re-organization of cortical areas, which are presumed to underlie the end of
      the sensitive period in congenitally deaf humans and cats. Finally, we present
      two clinical cases which demonstrate the use of the P1 cortical auditory evoked
      potential as a biomarker for central auditory system development and re
      organization in congenitally deaf children fitted with cochlear implants.
      LEARNING OUTCOMES: Readers of this article should be able to (i) describe the
      importance of the sensitive period as it relates to development of central
      auditory pathways in children with cochlear implants; (ii) discuss the hypothesis
      of de-coupling of primary from higher-order auditory cortex as it relates to the
      end of the sensitive period; (iii) discuss cross-modal re-organization which may
      occur after long periods of auditory deprivation; and (iv) understand the use of
      the P1 response as a biomarker for development of central auditory pathways.

PMID- 19380153
TI  - Antiplatelet therapy in ischemic stroke: variability in clinical trials and its
      impact on choosing the appropriate therapy.
AB  - Antiplatelet therapy is an integral component of effective secondary prevention
      after non-cardioembolic ischemic stroke. Numerous clinical trials have tested the
      efficacy and safety of different antiplatelet regimens, including aspirin
      monotherapy, clopidogrel monotherapy, the combination of aspirin plus
      clopidogrel, and the combination of aspirin plus dipyridamole, in patients with a
      history of arterial ischemic stroke and transient ischemic attack (TIA). Although
      competing, head-to-head comparisons between aspirin plus dipyridamole and
      clopidogrel were not previously available, various professional societies have
      outlined evidence-based recommendations for antiplatelet therapy in patients with
      ischemic stroke or TIA. Based on these guidelines, many experts in the field
      implicitly assumed that aspirin plus extended-release dipyridamole was the most
      effective antiplatelet treatment for stroke patients. However, these assumptions
      were called into question upon publication of the results from the Prevention
      Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The results of
      PRoFESS thus highlight the pitfalls of making conclusions of relative therapy
      efficacy in the absence of head-to-head comparisons. This article presents an
      overview of the factors that differ between clinical trials and "real-world"
      patient populations, as well as factors that differ among clinical trials
      themselves. The article also addresses the potential impact these differences may
      have on clinical trial results and subsequent clinical decision making.

PMID- 19380154
TI  - Intrinsic innervation of the horse ileum.
AB  - This paper describes the morphology and distribution of the enteric nervous
      system (ENS) cells and fibres immunoreactive for choline acetyltransferase
      (ChAT), neuronal nitric oxide synthase (nNOS), substance P (SP), calcitonin gene
      related peptide (CGRP), NF200kDa (NF200), and S100 protein. The percentages of
      subclasses of enteric neurons in the total neuronal population were investigated
      by the use of anti-PGP 9.5 or anti-NSE antibodies. ChAT-IR myenteric plexus (MP)
      and submucosal plexus (SMP) neurons were 66+/-7% and 74+/-15%, respectively,
      whereas those cells expressing nNOS-IR were 38+/-7% and 5+/-1%, respectively. MP
      and SMP neurons expressing both phenotypes were also present. SP-IR was expressed
      by 14+/-13% of MP and 66+/-8% of SMP neurons whereas CGRP-IR was observed only in
      the SMP (43+/-6%). NF200-IR was expressed by 61+/-15% and 91+/-10% of the MP and
      SMP neurons, respectively. The majority of the CGRP-IR SMP neurons expressed also
      SP-IR. Almost all SP-IR neurons in both the plexuses were cholinergic. The
      present study quantifies the main neuronal subpopulations of the ENS of the horse
      ileum; these data might be utilized to understand the neuronal modifications
      which occur in several gastrointestinal tract disorders.

PMID- 19380155
TI  - Hematology and serum biochemistry comparison in wild and captive Central American
      river turtles (Dermatemys mawii) in Tabasco, Mexico.
AB  - Hematological and serum biochemistry analyses were determined on 51 Central
      American river turtles (Dermatemys mawii) during the dry and rainy seasons of
      2006. Turtles came from two sites: Pantanos de Centla Biosphere Reserve and a
      turtle breeding farm, both located in Tabasco State, Mexico. Physical examination
      and body measures of animals were performed. Incidence and prevalence of
      hemoparasites were explored. Captive organisms were in poor physical condition
      while wild turtles were apparently healthy. There were differences in several
      hematological parameters related with the condition and the season. During the
      dry season captive turtles exhibited higher levels of uric acid and urea, as well
      as lower levels of glucose. Haemogregarina sp. was detected in 100% of the wild
      individuals, but not in captive individuals. Its incidence was greater during the
      rainy season. This is the first health assessment and hematology study of this
      critically endangered species.

PMID- 19380156
TI  - Energy recovery in wastewater decontamination: simultaneous photocatalytic
      oxidation of an organic substrate and electricity generation.
AB  - The contemporary removal of organic pollutants from aqueous solution and
      electricity generation is studied in the present work by means of an experimental
      device resulting from the combination of a photocatalytic reactor and an
      electrochemical cell. The proposed system relies on the capability of Cu2+ ions
      to reduce in the presence of TiO2, (solar) UV radiations and a sacrificial
      organic agent. In the anodic solution of the combined photoreactor-cell, Cu0 is
      oxidized to Cu2+ and the latter is reduced again to the lowest oxidation state.
      The use of different sacrificial agents ranging from formic acid (FA) to glycerol
      (GLY) to glucose (GLU) is investigated along with the adoption of two different
      cathodes for the cell, the first based again on the couple Cu2+/Cu0 and the
      second on the couple O2/H2O.

PMID- 19380157
TI  - Temperature effects on glycogen accumulating organisms.
AB  - Glycogen accumulating organisms (GAO) compete for substrate with polyphosphate
      accumulating organisms (PAO), which are the microorganisms responsible for the
      enhanced biological phosphorus removal (EBPR) in activated sludge wastewater
      treatment systems. This can lead to the deterioration of the EBPR process. In
      this paper, the long-term temperature effects on the anaerobic and aerobic
      stoichiometry and conversion rates on adapted enriched cultures of Competibacter
      (a known GAO) were evaluated from 10 to 40 degrees C. The anaerobic stoichiometry
      of Competibacter was constant from 15 to 35 degrees C, whereas the aerobic
      stoichiometry was insensitive to temperature changes from 10 to 30 degrees C. At
      10 degrees C, likely due to the inhibition of the anaerobic conversions of
      Competibacter, a switch in the dominant bacterial population to an enriched
      Accumulibacter culture (a known PAO) was observed. At higher temperatures (35 and
      40 degrees C), the aerobic processes limited the growth of Competibacter. Due to
      the inhibition or different steady-state (equilibrium) conditions reached at long
      term by the metabolic conversions, the short- and long-term temperature
      dependencies of the anaerobic acetate uptake rate of Competibacter differed
      considerably between each other. Temperature coefficients for the various
      metabolic processes are derived, which can be used in activated sludge modeling.
      Like for PAO cultures: (i) the GAO metabolism appears oriented at restoring
      storage pools rather than fast microbial growth, and (ii) the aerobic growth rate
      of GAO seems to be a result of the difference between PHA consumption and PHA
      utilization for glycogen synthesis and maintenance. It appears that the
      proliferation of Competibacter in EBPR systems could be suppressed by adjusting
      the aerobic solids retention time while, aiming at obtaining highly enriched PAO
      cultures, EBPR lab-scale reactors could be operated at low temperature (e.g. 10
      degrees C).

PMID- 19380158
TI  - Imposex and gender-independent butyltin accumulation in the gastropod Nassarius
      reticulatus from the Cantabrian coast (N Atlantic Spain).
AB  - The gastropod Nassarius reticulatus has been used as a tributyltin (TBT)
      biomonitor over the last two decades, and it is now endorsed by Atlantic Europe
      environmental agencies. However, there is one important question debated by the
      earliest studies still unresolved, namely whether butyltin accumulation in
      tissues is sex-dependent or not. Thus, a field survey was conducted along the
      Cantabrian coast: samples were subject to both customary imposex and modern
      chemical analyses. No significant bioaccumulation differences between sexes were
      found for any of the three butyltin species examined (i.e. TBT plus derivatives
      di- and mono-butyltin). In addition, both lower-than-expected absolute butyltins
      and minor relative TBT proportions in tissues conform with decreasing pollution
      in nearby areas. Imposex, though, is generally still considerable due to a lesser
      responsiveness of population indexes. Finally, one sample showed no sign of
      imposex but quantifiable butyltins; these are good news indicating that TBT is
      getting back down to levels around the induction threshold of this specific
      biological effect.

PMID- 19380159
TI  - Comparison of high specificity with standard versions of a quantitative latex D
      dimer test in the assessment of community pulmonary embolism: HaemosIL D-dimer HS
      and pulmonary embolism.
AB  - BACKGROUND: D-dimer assays are sensitive but have poor specificity. False
      positive results lead to extra imaging and hospital admissions. OBJECTIVES: To
      make a pilot comparison of the diagnostic accuracy of the standard quantitative
      latex HemosIL D-dimer assay with a newer HemosIL D-dimer HS version designed to
      have improved specificity. PATIENTS / METHODS: Consecutive patients presenting
      from the community to an Emergency Department that were investigated for
      suspected pulmonary embolism using a D-dimer test were included in the study.
      Standard and D-dimer HS tests were performed. Pulmonary Embolism was diagnosed on
      the basis of imaging studies or post-mortem at any time from presentation to 90
      days thereafter. RESULTS: The prevalence of Pulmonary Embolism was 4.5% (18/402).
      The sensitivity, specificity, negative predictive value, and positive predictive
      value for the standard quantitative D-dimer test was 100% (81.5 - 100.0), 49.2%
      (44.1 - 54.3),100% (98.1 - 100.0), and 8.5% (5.1 - 13.0), respectively, and 100%
      (81.5 - 100.0), 58.3% (53.2 - 63.3),100% (98.4 - 100.0), and 10.1% (6.1 - 15.5),
      for the D-dimer HS test. There were 35 (16%) fewer 'false positives' using the D
      dimer HS assay compared with the standard assay. CONCLUSIONS: D-dimer HS has
      superior specificity to the standard quantitative D-dimer test without any loss
      of sensitivity. The generation of fewer false positive results should lead to
      less unnecessary diagnostic imaging; the use of which is associated with
      increased hospital admissions and length of stay. The HS assay may therefore have
      significant health economic benefits.

PMID- 19380160
TI  - Development of vitrified porcine primordial follicles in xenografts.
AB  - The objective was to cryopreserve porcine primordial follicles by vitrification
      and to assess the development of these follicles in xenografts. Ovarian tissues
      containing primordial follicles were collected from neonatal (15-d-old) piglets.
      They were vitrified in modified tissue culture medium (TCM)-199 containing 15%
      (v/v) ethylene glycol, 15% (v/v) dimethylsulfoxide, 20% (v/v) fetal calf serum,
      and 0, 0.25, or 0.5M sucrose. After 1 wk of storage in liquid nitrogen (LN(2)),
      the tissues were warmed, and the morphology of follicles and oocytes was examined
      histologically. After vitrification in sucrose-free medium, there were 50+/-2
      (mean+/-SEM; n=10) follicles per tissue, in contrast with 108+/-10 (n=10) in
      fresh tissues. Losses were attributed to puncturing oocytes during the
      vitrification-warming process, as oocytes were apparently normal after treatment
      of the sucrose-free vitrification solution without plunging into LN(2). When
      tissues were vitrified in sucrose-supplemented medium, loss of oocytes decreased
      (P<0.05). However, the number of abnormal oocytes having nuclear shrinkage was
      increased (P<0.05) by the addition of 0.5M sucrose; this occurred in a small
      number of oocytes treated with sucrose-supplemented vitrification solutions
      without vitrification. After 2 mo of xenografting of vitrified-warmed tissues in
      SCID (severe combined immune deficiency) mice, primordial follicles developed to
      the secondary stage (accompanied by oocyte growth), whereas there was development
      to the antral stage in xenografts of fresh tissues. In conclusion, primordial
      follicles from neonatal pigs maintained their developmental ability after
      vitrification and warming, although their developmental rate was slower than that
      of the fresh control in xenografts.

PMID- 19380161
TI  - The influence of the pure metal components of four different casting alloys on
      the electrochemical properties of the alloys.
AB  - OBJECTIVES: The aim of this study was to investigate the influence of the pure
      metal components of the four different casting alloys on the corrosion behaviors
      of these alloys tested. METHODS: Potentiodynamic polarization tests were carried
      out on four different types of casting alloys and their pure metals at 37 degrees
      C in an artificial saliva solution. The ions released from the alloys into the
      solutions during the polarization test were also determined quantitatively using
      inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Ni-Cr (M1) and Co
      Cr (M2) alloys had a more homogenous structure than palladium based (M3) and gold
      based (M4) alloys in terms of the pitting potentials of the casting alloys and
      those of the pure metals composing the alloys. The total ion concentration
      released from M3 and M4 was less than from M1 and M2. This may be because M3 and
      M4 alloys contained noble metals. It was also found that the noble metals in the
      M3 and M4 samples decreased the current density in the anodic branch of the
      potentiodynamic polarization curves. In other words, noble metals contributed
      positively to dental materials. SIGNIFICANCE: Corrosion resistance of the casting
      alloys can be affected by the pure metals they are composed of. Au and Pd based
      noble alloys dissolved less than Ni-Cr and Co-Cr based alloys.

PMID- 19380162
TI  - Gene expression in the lamellar dermis-epidermis during the developmental phase
      of carbohydrate overload-induced laminitis in the horse.
AB  - OBJECTIVE: Gene expression in the lamellar dermis and epidermis was compared
      between healthy horses and horses in the developmental phase of carbohydrate
      overload-induced laminitis, in order to better understand the local biochemical
      and cellular events involved in the pathogenesis of laminitis. ANIMALS: Six
      healthy adult horses, with no history or clinical evidence of laminitis.
      PROCEDURES: Horses were randomly divided into two groups: control (n=3) and
      laminitis (n=3). Control horses received no treatment and were humanely
      euthanatized at the same time as the laminitis group. Horses in the laminitis
      group were given oligofructose (10g/kg bwt by nasogastric tube) and humanely
      euthanatized 24-30h later, before any clinical signs of laminitis were apparent.
      Sections of lamellar dermis and epidermis were harvested from the dorsal hoof
      wall of each horse immediately after death and cryopreserved until analysis. A
      bovine microarray chip, comprising approximately 15,000 genes, was used to
      compare gene expression between laminitis and control groups. RESULTS: A total of
      155 genes were up-regulated in the laminitis group. No genes were down-regulated.
      Genes coding for the production of pro-inflammatory biochemical or cellular
      processes and those involved in protein degradation/turnover predominated.
      Several regulatory or anti-inflammatory genes were also up-regulated. CONCLUSIONS
      AND CLINICAL RELEVANCE: Generation of inflammatory mediators within the lamellar
      tissues occurred before the development of substantial dermal-epidermal
      separation, inflammatory infiltrate, or vascular changes, and before the horses
      began showing signs of foot pain. While further studies are needed, early and
      targeted anti-inflammatory therapy may halt or prevent the development of
      laminitis in at-risk individuals.

PMID- 19380163
TI  - Pediatric endonasal endoscopic dacryocystorhinostomy.
AB  - Dacryocystorhinostomy (DCR) in children is indicated in cases of common
      congenital nasolacrimal duct obstruction (CNLDO) unresponsive to medical therapy,
      probing or intubation. The purpose of this manuscript is to evaluate the
      effectiveness of endonasal endoscopic pediatric DCR. The authors present a series
      of eight children (seven boys and one girl) who underwent a pediatric endonasal
      DCR between September 2007 and December 2008. The mean age was: 4.3 years (range:
      8 months to 9 years old). Three children had a craniofacial abnormality. There
      were ten primary DCRs and one revision DCR. In nine cases, the indication was a
      pure primary low mechanical obstruction persistent after one or more probings. In
      the 10th case there was also a stenosis of the inferior canaliculus diagnosed
      during the DCR. The revision DCR was indicated because of the closure of the
      stoma created 3 years ago. A silicone intubation was put in place only in two
      cases: in case of a stenosis of the inferior canaliculus (3 months) and the other
      in case of revision DCR (1 month). The follow-up for primary DCRs was 10.5 months
      (range: 6-15) and for revision surgery 6 months (after the retrieve of the
      stent). In primary DCRs, there was a complete resolution of symptoms in nine out
      of 10 cases. The 10th case experienced a transient slight epiphora during a viral
      rhinitis. In case of revision DCR, the child was free of symptoms. In conclusion
      pediatric DCR is a very effective and safe procedure for the treatment of a low
      mechanical obstruction of the lacrimal pathway in children unresponsive to
      previous probings. Stenosis of the inferior canaliculus can give some slight
      intermittent epiphora despite a wide and patent stoma. Moreover craniofacial
      abnormalities are more common in children than in adults undergoing a DCR.

PMID- 19380164
TI  - Evaluation of children with lymphatic malformations of the head and neck using
      the Cologne Disease Score.
AB  - OBJECTIVES: To assess the disease-related impairments of children with lymphatic
      malformations of the head and neck and their changes after therapy using the
      Cologne Disease Score (CDS). METHODS: 29 children with lymphatic malformations of
      the head and neck were evaluated regarding their symptoms before and after
      therapy using the CDS. The Wilcoxon test for dependent groups was used to compare
      the CDS at initial visit before treatment and last visit after treatment.
      RESULTS: The CDS of patients belonging to the moderate (initial CDS: more than
      eight points) and advanced disease group (initial CDS: five, six or seven points)
      significantly increased after therapy while the patients in the severe disease
      group (initial CDS: lower than four points) showed no significant improvement of
      CDS. Patients with stage IV and especially stage V lymphatic malformations
      according to de Serres showed considerably lower pre- and posttherapeutic CDS
      levels than those of stage I and II. CONCLUSIONS: The visual impairment is not
      mapped by the CDS, therefore item vision should be added to the CDS to make an
      evaluation of all lymphatic malformations of the head and neck possible. The
      present series could show that especially patients with a moderate or advanced
      disease according to the CDS may profit from therapeutic interventions.

PMID- 19380165
TI  - Sialodochostomy as treatment for imperforate submandibular duct: a systematic
      literature review and report of two cases.
AB  - OBJECTIVE: To better understand the diagnosis, treatments, and outcomes of
      congenitally imperforate salivary ducts. METHODS: A systematic literature review
      was performed using the following terms: imperforate submandibular duct,
      imperforate Wharton's duct, congenital atresia submandibular duct, congenital
      atresia sublingual duct, and congenital ranula. Only papers focusing on
      congenital floor of mouth cysts arising from imperforate salivary ducts were
      included. Two additional patients from our own experience are also discussed.
      RESULTS: Seventeen papers published since 1950 met inclusion criteria. A total of
      26 patients underwent therapy ranging from mere observation to complete excision
      of the cyst with the sublingual gland. Both of our 2 additional patients both
      underwent simple sialodochostomy (excision of the imperforate sublingual
      caruncle) with cyst decompression. For all 28 patients, there have been no
      reported recurrences, with mean follow-up of 24.8 months and median follow-up of
      14.8 months. CONCLUSIONS: Congenital floor of mouth cysts arising from
      imperforate salivary ducts are rare, but they may mimic the appearance of a
      ranula. Unlike ranulas, these cysts may be safely and effectively cured by simple
      sialodochostomy. To date, 26 other cases have been described in the literature,
      and nearly all have been successfully treated with simple incision or
      marsupialization without recurrence. Care should be taken to exclude ranula as a
      diagnosis, as incomplete excision may likely result in recurrence.

PMID- 19380166
TI  - Behavioral and electrophysiological measures of auditory change detection in
      children following late cochlear implantation: a preliminary study.
AB  - OBJECTIVE: The purpose of the current study was to longitudinally assess the
      development of automatic sound feature discrimination and compare it to
      behavioral discrimination in late-implanted cochlear implant users. METHODS:
      Scalp-recorded auditory evoked potentials (AEPs) and behavioral discrimination of
      frequency, duration and intensity differences within an oddball paradigm using
      complex stimuli were recorded in three late-implanted cochlear implant subjects
      beginning on turn-on day. RESULTS: Variable results were obtained in behavioral
      and AEPs that were consistent with the amount of pre-implant auditory experience
      each subject had. The best user showed rapid development of neurophysiologic
      indices of change detection along with improvement in behavioral and real-world
      auditory skills. In contrast, there were no recordable AEPs in the poorer CI user
      and there was little change in behavioral outcomes. CONCLUSION: There is evidence
      of utilization of usual auditory processing pathways in the AEPs of some children
      who receive cochlear implants late in their childhood. Some plasticity in the
      auditory cortical pathways may be present despite prolonged auditory deprivation
      in school-aged children who are late-implanted cochlear implant recipients.

PMID- 19380168
TI  - Computed tomography unmasks a phantom tumour.
AB  - We describe a patient with left sided congestive heart failure and a round-shaped
      mass on the chest X-ray. Using computed tomography, the mass is diagnosed as a
      phantom tumour consisting of loculated effusion in the interlobular fissure that
      vanishes after treatment for heart failure is initiated.

PMID- 19380169
TI  - Analysis of the method for conversion between levels of HbA1c and glycated
      albumin by linear regression analysis using a measurement error model.
AB  - AIM: To establish a method for conversion between HbA(1c) and glycated albumin
      (GA) using a measurement error model (MEM). METHODS: Type 2 diabetic patients,
      without complications that might affect either HbA(1c) or GA, were enrolled in
      the study (n=154, age 68.4+/-9.9). HbA(1c), GA and postprandial plasma glucose
      (PPG) levels were measured simultaneously on >or=3 occasions. RESULTS: PPG showed
      a significant correlation with HbA(1c) and GA (p<0.001 for both). Correlation
      between HbA(1c) and GA was very high (r=0.747, p<0.001). When the independent
      variable was assumed to be GA, common regression analysis yielded a regression
      line HbA(1c)=2.59+0.204GA. When the independent variable was changed to HbA(1c),
      the regression line became GA=2.26+2.74HbA(1c). The y-intercept of the first line
      was significantly positive, whereas that of the second was not. The regression
      line using MEM was HbA(1c)=1.73+0.245GA. The y-intercept was 1.73+/-0.38
      (p<0.001) and the slope was 0.245+/-0.018 (p<0.001), showing that 1% increase in
      HbA(1c) level corresponds to 4% increase in GA level. CONCLUSIONS: The
      relationship between HbA(1c) and GA was examined by regression analysis using
      MEM. HbA(1c) levels in Japan appear to have a positive shift of approximately
      1.7%. Incremental ratio 4 of GA vs. HbA(1c) showed good consistency with values
      derived from in vitro data.

PMID- 19380167
TI  - Decision by division: making cortical maps.
AB  - In the past three decades, mounting evidence has revealed that specification of
      the basic cortical neuronal classes starts at the time of their final mitotic
      divisions in the embryonic proliferative zones. This early cell determination
      continues during the migration of the newborn neurons across the widening
      cerebral wall, and it is in the cortical plate that they attain their final
      positions and establish species-specific cytoarchitectonic areas. Here, the
      development and evolutionary expansion of the neocortex is viewed in the context
      of the radial unit and protomap hypotheses. A broad spectrum of findings gave
      insight into the pathogenesis of cortical malformations and the biological bases
      for the evolution of the modern human neocortex. We examine the history and
      evidence behind the concept of early specification of neurons and provide the
      latest compendium of genes and signaling molecules involved in neuronal fate
      determination and specification.

PMID- 19380170
TI  - Correction of insulin resistance in chronic hepatitis C patients not responding
      to the standard of care: more questions than answers.

PMID- 19380171
TI  - Liver biopsy: the best standard...when everything else fails.

PMID- 19380172
TI  - Feature selection and syndrome prediction for liver cirrhosis in traditional
      Chinese medicine.
AB  - Traditional Chinese medicine (TCM) treatment is one of the safe and effective
      methods for liver cirrhosis. In the process of its treatment, a very important
      step, syndrome prediction is generally performed by physicians at present, which
      actually hinders the application prospects of TCM. Based on the data mining
      algorithm, a novel method called TCMSP (traditional Chinese medicine syndrome
      prediction) is proposed, which consists of two phases. In the first phase, based
      on an improved information gain method in multi-view, the critical features are
      filtered from the original features. In the second phase, the class label of a
      new case is predicted automatically based on accuracy-weighted majority voting.
      The proposed method is evaluated by the liver cirrhosis dataset, 20 critical
      features are selected from original 105 features and the corresponding syndromes
      of 138 new cases are identified respectively. The critical features are in sound
      agreement with those used by the physicians in making their clinical decisions.
      Finally, this new method is also demonstrated on three standard datasets (SPECT
      Heart, Lung Cancer and Iris) and the results are compared with some other
      methods. The experimental results show that TCMSP method performs well in the
      field of TCM diagnosis.

PMID- 19380173
TI  - Malignant pleural mesothelioma: genome-wide expression patterns reflecting
      general resistance mechanisms and a proposal of novel targets.
AB  - Malignant pleural mesothelioma is an asbestos-related multi-resistant tumour with
      increasing incidence worldwide. Well-characterized snap-frozen normal parietal,
      visceral pleura and mesothelioma samples were analysed with Affymetrix Human
      Genome U133 Plus 2.0 GeneChip oligoarray of 38500 genes. We discovered a close
      relation between gene profile and resistance towards topoisomerase poisons,
      alkylating agents, antitubulines, antifolates, platinum compounds and radiation
      therapy. Target genes of chemo- (e.g. TOP2A, BIRC5/Survivin and proteasome) and
      radiotherapy (e.g. BRCA2, FANCA, FANCD2, CCNB1 and RAD50) were significantly
      overexpressed. The Fanconi anemia/BRCA2 pathway, responsible for homologous
      recombination DNA repair appears as a key pathway in both chemo- and radio
      resistance of mesothelioma. Leukocyte trans-endothelial migration gene down
      regulation could partly explain resistance against immunological therapies. Gene
      expression features found in other resistant cancer types related to DNA repair
      and replication are shared by mesothelioma and could represent general features
      of tumour resistance. Targeted suppression of some of those key genes and
      pathways combined with chemotherapy or radiation could improve the outcome of
      mesothelioma therapy. We propose CHEK1, RAD21, FANCD2 and RAN as new co-targets
      for mesothelioma treatment. The pro-angiogenic AGGF1 mRNA and protein was highly
      overexpressed in all tumours and may serve as a target for anti-angiogenic
      treatment. Overexpression of NQO1 may render mesothelioma sensitive to the novel
      compound beta-Lapachone.

PMID- 19380174
TI  - FOXO3a elicits a pro-apoptotic transcription program and cellular response to
      human lung carcinogen nicotine-derived nitrosaminoketone (NNK).
AB  - Long-term carcinogen exposure exerts continuous pressure on key mechanisms that
      repair or eliminate carcinogen-damaged cells giving rise to selective failures
      that contribute to lung cancer. FOXO3a is a transcription factor that elicits a
      protective response to diverse cellular stresses. Although implicated as a tumor
      suppressor, its role in sporadic cancer is uncertain. We recently observed that
      FOXO3a gene inactivation occurs frequently in carcinogen-induced lung
      adenocarcinoma (LAC). This suggests that FOXO3a may play a role in LAC
      suppression by eliciting a protective response to carcinogenic stress. Here we
      investigated this possibility by examining the role of FOXO3a in the cellular
      response to nicotine-derived nitrosaminoketone (NNK), a lung carcinogen
      implicated as a cause of human LAC. We show that restoration of FOXO3a in FOXO3a
      deficient LAC cells increases sensitivity to apoptosis caused by a DNA-damaging
      intermediate of NNK. Prior to this cellular outcome, FOXO3a is functionally
      activated and mediates a large-scale transcription program in response to this
      damage involving a significant modulation of 440 genes. Genes most significantly
      represented in this program are those with roles in cell growth and
      proliferation>protein synthesis>gene expression>cell death>cell cycle. The
      results of this study show that FOXO3a directs an anti-carcinogenic transcription
      program that culminates in the elimination of carcinogen-damaged cells. This
      suggests that FOXO3a is a potential suppressor of carcinogenic damage in LAC.

PMID- 19380175
TI  - Cetuximab and gemcitabine in elderly or adult PS2 patients with advanced non
      small-cell lung cancer: The cetuximab in advanced lung cancer (CALC1-E and CALC1
      PS2) randomized phase II trials.
AB  - BACKGROUND: Two parallel randomized phase 2 trials were performed to choose the
      optimal way of combining cetuximab with gemcitabine in the first-line treatment
      of elderly (CALC1-E) and adult PS2 (CALC1-PS2) patients with advanced NSCLC.
      METHODS: Stage IV or IIIB NSCLC patients, aged > or =70 years with PS 0-2 for
      CALC1-E or aged <70 with PS2 for CALC1-PS2, not selected for EGFR expression,
      were eligible. Patients were randomized to concomitant (gemcitabine, for a
      maximum of 6 cycles, plus cetuximab until progression) or sequential
      (gemcitabine, for a maximum of 6 cycles, followed by cetuximab) strategy. A
      selection design, with 1-year survival rate as the primary endpoint, was applied,
      requiring 58 elderly and 42 PS2 patients. RESULTS: All planned patients were
      randomized. In sequential arms, 34.5% and 60.0% patients were not able to receive
      cetuximab after gemcitabine in CALC1-E and CALC1-PS2, respectively. Survival
      rates (95% CI) at 1-year for concomitant and sequential arms were 41.4% (23.5
      61.1) and 31.0% (15.3-50.8) in CALC1-E and 27.3% (10.7-50.2) and 35.0% (15.4
      59.2) in CALC1-PS2. In both studies, survival curves crossed at about 10 months
      and the worse arm until that time became the better one at 1-year. Toxicity was
      similar across treatment groups. In concomitant arm of CALC1-E (but not of CALC1
      PS2), survival was longer for patients who developed skin toxicity within the
      first two cycles of treatment. CONCLUSION: In both groups of patients, sequential
      strategy cannot be proposed for future trials because of low compliance.
      Inconsistency of survival outcomes makes also concomitant treatment not a
      candidate for further testing in unselected elderly and PS2 NSCLC patients.

PMID- 19380176
TI  - Phenolic metabolism of Matricaria chamomilla plants exposed to nickel.
AB  - We examined accumulation of phenolic acids, total soluble phenolics and
      flavonoids, and activities of phenolic metabolism-related enzymes (shikimate
      dehydrogenase (SKDH), phenylalanine ammonia-lyase (PAL), cinnamyl alcohol
      dehydrogenase (CAD), polyphenol oxidase (PPO)) in Matricaria chamomilla plants
      exposed to 3, 60 and 120 microM of nickel (Ni) for 10 days. Ni showed low
      toxicity as indicated by unaltered content of total soluble phenolics in the leaf
      rosettes. In the roots, the effects of Ni were more visible, including increased
      total phenolics and PAL activity, but a decrease in PPO activity was observed.
      CAD activity was not affected by any of the Ni concentrations. Cinnamic acid
      derivatives were affected more than benzoic acid derivatives. Accumulation of
      chlorogenic acid, an important antioxidant compound, was enhanced by Ni treatment
      (ca. 4-fold in 120 microM Ni). Accumulation of protocatechuic acid, a phenol with
      high chelating strength, even decreased in the leaf rosettes. These observations
      are discussed in connection to antioxidative properties of phenolic metabolites
      and previously tested metals (cadmium and copper).

PMID- 19380177
TI  - Bactericidal efficacy of a 1.5min surgical hand-rubbing protocol under in-use
      conditions.
AB  - In healthy volunteers, surgical hand rubbing with Sterillium for 1.5min has been
      shown to be as effective as a 3min procedure. The aim of this study was to assess
      whether this result was reproducible under in-use conditions. During nine weeks
      in the ambulatory surgery theatre of a 750-bed tertiary care university hospital,
      the two surgical hand-rubbing procedures were compared with each other, and with
      a hand-scrubbing procedure using a povidone-iodine (4%) scrub prior to and after
      25 different surgical operations for each. Imprints of the surgeon's dominant
      hand were taken on culture plates before and within 1min following the end of the
      hand-rubbing/scrubbing procedures (immediate effect) and at the end of surgery
      (sustained effect). Plates were incubated aerobically at 37 degrees C for 48h.
      Colonies were counted at 24h and 48h. Results were expressed as the number of
      colony-forming units per hand. No significant difference in baseline hand
      bacterial load was found before the hand-rubbing/scrubbing procedures among the
      three groups (P=0.19). With respect to immediate and sustained antimicrobial
      effects, a significantly greater reduction in microbial loads on the hands was
      achieved with the 3min hand-rubbing protocol as opposed to hand-scrubbing
      protocol (P=0.04 and P=0.02, respectively), but there was no difference between
      the reductions obtained with 1.5 and 3min rubbing protocols (P=0.41 and P=0.36,
      respectively). Surgical hand rubbing with Sterillium using a 1.5min protocol
      should be considered as an attractive alternative method for surgical hand
      disinfection.

PMID- 19380178
TI  - Norovirus infection as a cause of sporadic healthcare-associated diarrhoea.

PMID- 19380179
TI  - Analysis of neonatal nosocomial infection rates across the Australian and New
      Zealand Neonatal Network.
AB  - This paper describes the variation in neonatal nosocomial infection rates across
      26 contributing units of the Australian and New Zealand Neonatal Network. Data
      collected during the years 2002-2004 have been analysed comprising a total of
      3180 infants of <1000g birthweight and 260,694 hospital-days. Overall infection
      rates of 5.02 [95% confidence interval (CI): 4.75, 5.30] infections per 1000 days
      total admission for infants of <1000g birthweight are comparable with other
      published data. Censoring data to the first 35 days of admission demonstrated an
      infection rate of 13.88 (95% CI: 13.14, 14.65) infections per 1000 days. A
      standardised, expected, infection rate for each unit was calculated by correcting
      for gestational age and gender. Analysis of the difference between observed and
      expected infection rates demonstrated considerable variation in nosocomial
      infection rates between participating units. Three units demonstrated a
      nosocomial infection rate significantly (P<0.005) below the population value.
      Further analysis of clinical practice variations within these units may uncover
      potential beneficial practices for the network.

PMID- 19380180
TI  - Survey of gut colonisation with Stenotrophomonas maltophilia among neonates.

PMID- 19380182
TI  - Infection control: a hospice perspective.
AB  - Infection prevention and control is paramount to securing patient safety within a
      healthcare establishment. Independent sector hospices in the south east of
      England provide specialist palliative care and must be able to demonstrate risk
      reducing strategies in order to comply with their registering body and the UK
      Health Act (2006). Using the clinical governance framework ensures that policies,
      processes and procedures are in place. Universal practices should be standard and
      ensure that current evidenced-based knowledge is imparted toward these aims. This
      is achieved through educational programmes and regular updates for new and
      existing staff. The ultimate aim is to reduce the spread of cross-infection from
      healthcare staff to patients.

PMID- 19380181
TI  - Reducing surgical site infection incidence through a network: results from the
      French ISO-RAISIN surveillance system.
AB  - Surgical-site infections (SSIs) are a key target for nosocomial infection control
      programmes. We evaluated the impact of an eight-year national SSI surveillance
      system named ISO-RAISIN (infection du site operatoire - Reseau Alerte
      Investigation Surveillance des Infections). Consecutive patients undergoing
      surgery were enrolled during a three-month period each year and surveyed for 30
      days following surgery. A standardised form was completed for each patient
      including SSI diagnosis according to standard criteria, and several risk factors
      such as wound class, American Society of Anesthesiologists (ASA) score, operation
      duration, elective/emergency surgery, and type of surgery. From 1999 to 2006,
      14,845 SSIs were identified in 964,128 patients (overall crude incidence: 1.54%)
      operated on in 838 participating hospitals. The crude overall SSI incidence
      decreased from 2.04% to 1.26% (P<0.001; relative reduction: -38%) and the
      National Nosocomial Infections Surveillance system (NNIS)-0 adjusted SSI
      incidence from 1.10% to 0.74% (P<0.001; relative reduction: -33%). The most
      significant SSI incidence reduction was observed for hernia repair and caesarean
      section, and to a lesser extent, cholecystectomy, hip prosthesis arthroplasty,
      and mastectomy. Active surveillance striving for a benchmark throughout a network
      is an effective strategy to reduce SSI incidence.

PMID- 19380183
TI  - Biological hazards among police workers: a hospital-based prevention programme.

PMID- 19380184
TI  - Synthesis and antimicrobial properties of polymerizable quaternary ammoniums.
AB  - Introduction of biocide monomers during the process of polymerization is a
      promising approach in the development of new permanent non leaching biocide
      materials. Two series of surfactants monomers, with a quaternary ammonium group
      as polar head and an acrylic function as the polymerizable moiety, were
      synthesized and tested to evaluate their surface active properties alongside with
      their antibacterial and antifungal properties. Four microbial strains were used
      to perform the study: Pseudomonas aeruginosa, Staphylococcus aureus, Candida
      albicans and Aspergillus niger. The biocidal efficacy measured by bacterial and
      fungal growth inhibition expressed as MIC (Minimal Inhibitory Concentration) and
      MLC (Minimal Lethal Concentration) values was discussed as a function of
      molecular parameters. All the synthesized surfactant monomers presented
      bactericidal and fungicidal activities. Increasing the spacer between the acrylic
      part and the ammonium group has a favourable effect on the MIC and MLC results.

PMID- 19380185
TI  - A new approach to estimate nuclide ratios from measurements with activities close
      to background.
AB  - Measurements of low-level radioactivity often give results of the order of the
      detection limit. For many applications, interest is not only in estimating
      activity concentrations of a single radioactive isotope, but focuses on multi
      isotope analyses, which often enable inference on the source of the activity
      detected (e.g. from activity ratios). Obviously, such conclusions become
      questionable if the measurement merely gives a detection limit for a specific
      isotope. This is particularly relevant if the presence of an isotope, which shows
      a low signal only (e.g. due to a short half-life or a small transition
      probability), is crucial for gaining the information of interest. This paper
      discusses a new approach which has the potential to solve these problems. Using
      Bayesian statistics, a method is presented which allows statistical inference on
      nuclide ratios taking into account both prior knowledge and all information
      collected from the measurements. It is shown that our method allows quantitative
      conclusion to be drawn if counts of single isotopes are low or become even
      negative after background subtraction. Differences to the traditional statistical
      approach of specifying decision thresholds or detection limits are highlighted.
      Application of this new approach is illustrated by a number of examples of
      environmental low-level radioactivity measurements. The capabilities of our
      approach for spectrum interpretation and source identification are demonstrated
      with real spectra from air filters, sewage sludge and soil samples.

PMID- 19380186
TI  - Temporal variation of (7)Be concentrations in atmosphere for 8y from 2000 at
      Yamagata, Japan: solar influence on the (7)Be time series.
AB  - We have been continuously observing the daily (7)Be concentrations in surface air
      at Yamagata, Japan (38.25 degrees N, 140.35 degrees E) since 2000. The yearly
      profile of the (7)Be concentration indicates the variation in galactic cosmic
      rays owing to solar modulation. Over 8y, the (7)Be concentration, cosmic
      neutrons, and number of sunspots varied by 37.4%, 12.2%, and 92.8%, respectively.
      The influence of precipitation on the (7)Be variability was approximately 5%.
      Hence, the yearly (7)Be concentration was mainly varied by the solar modulation
      of the (7)Be production rates. Based on the production rates found in an EXPACS
      simulation, the observed variability indicates (7)Be transport from high
      latitudes. The daily (7)Be concentrations have two significant periodic
      components of 19d and 36d. The 36-d component implies a relationship between the
      sun's rotation and the vertical transport of air masses under quiet solar
      activity.

PMID- 19380187
TI  - Influence of molar support loss on stress and strain in premolar periodontium: a
      patient-specific FEM study.
AB  - OBJECTIVES: To test the hypothesis that loss of molar support causes increased
      stress and strain in the periodontal structures surrounding the premolars, and to
      assess the influence of denture use on stress distribution. METHODS: Subjects
      included female patients with unilateral and bilateral loss of mandibular molar
      teeth and controls with complete dentition (n=7 in each group). The subjects
      included had normal dentition mesial to the edentulous region and use of a lower
      free-end saddle removable partial denture. Occlusal contacts were registered in
      vivo, and a patient-specific finite element model was constructed for each
      subject based on morphological measurements of the diagnostic cast and
      radiographs. The maximum bite force on each tooth was then used to calculate the
      stress and strain on the cortical and the cancellous bone. RESULTS: Mean maximum
      bite force and maximum principal stress and strain on periodontal tissues of the
      second premolars were significantly higher in the bilateral molar loss group than
      those in the other groups (p<0.05). The increase in stress could not be prevented
      by wearing dentures. The mean maximum stress and strain per bite force were
      relatively constant among the groups, indicating that the increased maximum
      stress and strain in the bilateral molar loss group was attributed to the higher
      maximum bite force. CONCLUSIONS: The results suggest that the periodontium
      surrounding the most posteriorly located occluding premolars may become sensitive
      to bilateral loss of molar support when patients exhibit higher maximum bite
      forces.

PMID- 19380188
TI  - Randomized study of bipolar vessel sealing system versus conventional suture
      ligature for vaginal hysterectomy.
AB  - OBJECTIVE: This study was undertaken to compare the use of bipolar vessel sealing
      system (BVSS) with conventional suture ligature in vaginal hysterectomy (VH) on a
      non-prolapsed uterus. STUDY DESIGN: Women referred for VH for uterine myoma were
      randomized to BVSS (n=45) or conventional suture ligature VH (n=45). Exclusion
      criteria were uterine prolapse and indication associated surgical procedures.
      Main outcome measures were operative time, blood loss, hospital stay, pain
      status, peri and post-operative complications. Data of patients were collected
      prospectively. Statistical analysis was performed using chi-square and Student's
      t-test as appropriate. RESULTS: There were no differences in patients' mean age,
      parity and uterine size between groups. Patients in the BVSS group had a
      significantly reduced operating time (29.2+/-2.1 min vs. 75.2+/-5 min; p<0.001),
      operative blood loss (84+/-5.9 mL vs. 136.4+/-89.1 mL; p=0.001), requirement of
      surgical sutures (1.2+/-0.6 units vs. 7.4+/-0.3 units; p<0.001), pain status
      (1.6+/-0.4 vs. 3.6+/-0.4; p<0.001) and hospital stay (25.6+/-0.9h vs. 33.2+/
      1.7h; p<0.001) compared to the control group. The overall complication rate in
      the study was 7.8% (7/90), and did not differ between patients of the BVSS and
      control group. CONCLUSION: Bipolar vessel sealing for vaginal hysterectomy
      appears to be an effective and safe haemostatic control method, with reduced
      operating time, peri-operative blood losses, post-operative pain and hospital
      stay.

PMID- 19380189
TI  - Conformation and dynamics of DNA molecules during photoreversible condensation.
AB  - Direct observation of the mechanism and dynamics of photo-initiated DNA
      compaction and re-expansion using a light-responsive cationic surfactant has been
      achieved with fluorescence microscopy. The surfactant undergoes a reversible
      photoisomerization upon exposure to visible (trans isomer, relatively
      hydrophobic) or UV (cis isomer, relatively hydrophilic) light. Thus, surfactant
      binding to DNA and the DNA condensation that result can both be initiated and
      controlled with light illumination. The inherent kinetics of DNA conformational
      changes, directly visualized following the in situ light "trigger" of surfactant
      photoisomerization, are found to occur at rates of approximately 9 microm/s or
      240 kbp/s, at or near rates that can be achieved in natural processes.
      Furthermore, observation of photo-initiated DNA compaction, free of the effects
      of shear or mixing, provides evidence of a condensation mechanism that nucleates
      at the ends of the macromolecule. Ethidium bromide displacement studies, employed
      to gain insight on the mode of interaction between the photo-surfactant and DNA,
      also reveal the importance of both electrostatic and hydrophobic forces in
      surfactant binding and DNA condensation.

PMID- 19380190
TI  - Overexpression of DLC-1 induces cell apoptosis and proliferation inhibition in
      the renal cell carcinoma.
AB  - The lack of effective anti-tumor therapy for renal cell carcinoma (RCC) has
      stimulated the search for novel target whose inhibition could block
      tumorigenesis. Recently, reduced DLC-1 has been shown to be associated with
      aggressive and highly metastatic renal cell carcinoma. In this study, the
      biological role of DLC-1 on cell growth, migration and cell cycle progression in
      RCC cells was investigated. Over-expression of DLC-1 was associated with a marked
      inhibition of cell growth (P<0.01). The inhibitory effect was partly due to the
      induction of apoptosis and cell cycle arrest in G(0)/G(1) accompanied by up
      regulation of the intracellular signal proteins of p27 and down-regulation of
      cyclin D1 and cyclin E. Furthermore, DLC-1 induced FAK dephosphorylation of focal
      adhesion proteins inhibited cell migration (P<0.05). Decreased DLC-1 expression
      strongly correlated with proliferative activity, as indicated by the elevated
      levels of Ki67. Restoration of DLC-1 expression in RCC cells led to Bcl-2 and
      caspase-3 mediated apoptosis as well as attenuated the ability of the cells to
      form RCC tumors in athymic nude mice (P<0.05). Taken together, these results
      suggest that DLC-1 plays a crucial role in signal transduction pathway regulating
      the cell proliferation, migration, and carcinogenesis of human RCC.

PMID- 19380191
TI  - Epidermal growth factor competes with EGF receptor inhibitors to induce cell
      death in EGFR-overexpressing tumor cells.
AB  - Epidermal growth factor receptor (EGFR) signaling plays an important role in cell
      growth and differentiation. Mutations in the EGFR gene and EGFR gene
      amplifications have been associated with increased responsiveness to selective
      EGFR tyrosine kinase inhibitors (EGFR-TKIs). By contrast, EGF may also stimulate
      apoptosis in tumor cells, depending on EGFR and Her2 (erbB-2) expression levels.
      In the present study, we investigated cellular responses after EGFR activation by
      EGF, or inhibition by cetuximab and gefitinib. EGF treatment induced a near
      immediate increase in p38 MAPK phosphorylation together with inactivation of
      ERK1/2. In contrast, gefitinib- and cetuximab-induced phosphorylation of p38 MAPK
      was much delayed, and gefitinib also induced a delayed activation of ERK1/2. EGF
      induced progressive cell death of A431 cells with prolonged treatment, whereas
      cetuximab- or gefitinib-treated cells showed temporary growth arrest and
      subsequent re-growth. Moreover, in combination treatment experiments, cetuximab
      or gefitinib competitively inhibited EGF-induced cell death. Normal WI38-VA13
      cells did not display any noticeable changes in cell proliferation in response to
      EGF, gefitinib or cetuximab. EGF-induced death signaling is apparently
      irreversible: EGF induced significant EGFR phosphorylation/internalization and
      activated caspase-3, -8 and -9, effects that were not observed in cetuximab- or
      gefitinib-treated cells. Collectively, these results indicate that EGF may be a
      more potent cytotoxic agent than EGFR blockers in EGFR-overexpressing cancer
      cells.

PMID- 19380192
TI  - Anti-survivin antibody responses in lung cancer.
AB  - Existing evidence regarding spontaneous anti-survivin humoral responses in lung
      cancer is inconclusive. Moreover, despite that cancer cell death elicited by
      radiotherapy and some chemotherapeutic agents seems to be immunogenic,
      information about the possible effect of treatment on these responses, is
      lacking. Serum samples from 33 small cell lung cancer (SCLC) and 117 non-small
      cell lung cancer (NSCLC) patients upon diagnosis, and from 100 controls, were
      tested by ELISA for anti-survivin antibodies. Cutoff was set to the mean+2SD of
      controls. 7.7% of NSCLC, none of the SCLC patients and 2% of the controls
      appeared with elevated antibody levels (OR 3.6, 95% CI 0.7-17.3 for NSCLC, OR
      0.6, 95% CI 0.03-12.6 for SCLC). Measurement of antibodies in 76 NSCLC patients
      post therapies and during their follow-up, revealed that in 12 NSCLC patients the
      antibody levels increased up to 2-38 times, and in seven others, they decreased
      by 2-8 times. No significant correlation was uncovered between either the
      antibody levels upon diagnosis or their changes post therapies and during follow
      up, and any clinicopathological parameter, their response to therapy and
      survival. Survivin does not induce considerable humoral responses in lung cancer.
      Potentially, however, strong anti-survivin antibody responses can be elicited
      during the post therapy and follow-up of the patients, whose clinical
      significance remains to be elucidated. These findings, together with our previous
      data concerning survivin expression and the related cytolytic T cell responses in
      lung cancer, signify a high tolerogenic potential of this tumor-associated
      antigen.

PMID- 19380193
TI  - Removal of transition metal ions from aqueous solutions by adsorption onto a
      novel silica gel matrix composite adsorbent.
AB  - This paper presented the synthesis of a novel composite adsorbent silica gel
      microspheres encapsulated with 5-sulfosalicylic acid functionalized polystyrene
      (SG-PS-azo-SSA). It was characterized by titration method, FT-IR (Fourier
      transform infrared spectrometer), SEM (scanning electron microscope), EDXAS
      (energy dispersive X-ray analysis system), etc. SG-PS-azo-SSA has been used to
      investigate the adsorption of Mn(II), Fe(III), Co(II), Ni(II), Zn(II), Cd(II),
      Hg(II), Pd(II), Cu(II), Ag(I) and Au(III) from aqueous solutions. The research
      results revealed that SG-PS-azo-SSA has the better adsorption capacity for
      Cu(II), Ag(I) and Au(III). Langmuir and Freundlich isotherm models were applied
      to analyze the experimental data and the adsorption of Cu(II), Ag(I) and Au(III)
      on SG-PS-azo-SSA fitted well to the Langmuir isotherm equation. The obtained
      maximum adsorption capacity for Cu(II), Ag(I), and Au(III) is 0.472 mmol/g, 0.822
      mmol/g and 0.810 mmol/g, respectively. Thus, silica gel encapsulated by 5
      sulfosalicyclic acid functionalized polystyrene (SG-PS-azo-SSA) is favorable and
      useful for the removal of Cu(II), Ag(I) and Au(III) metal ions.

PMID- 19380194
TI  - Layered double hydroxides as adsorbents and carriers of the herbicide (4-chloro-2
      methylphenoxy)acetic acid (MCPA): systems Mg-Al, Mg-Fe and Mg-Al-Fe.
AB  - Hydrotalcite-like compounds [Mg(3)Al(OH)(8)]Cl x 4H(2)O; [Mg(3)Fe(OH)(8)]Cl x
      4H(2)O; [Mg(3)Al(0.5)Fe(0.5)(OH)(8)]Cl x 4H(2)O (LDHs) and calcined product of
      [Mg(3)Al(OH)(8)]Cl x 4H(2)O, Mg(3)AlO(4.5) (HT500), were studied as potential
      adsorbents of the herbicide MCPA [(4-chloro-2-methylphenoxy)acetic acid] as a
      function of pH, contact time and pesticide concentration, and also as support for
      the slow release of this pesticide, with the aim to reduce the hazardous effects
      that it can pose to the environment. The information obtained in the adsorption
      study was used for the preparation of LDH-MCPA complexes. The results showed high
      and rapid adsorption of MCPA on the adsorbents as well as that MCPA formulations
      based on LDHs and HT500 as pesticide supports displayed controlled release
      properties and reduced herbicide leaching in soil columns compared to a standard
      commercial MCPA formulation. Thereby, we conclude that the LDHs employed in this
      study can be used not only as adsorbents to remove MCPA from aqueous solutions,
      but also as supports for the slow release of this highly mobile herbicide, thus
      controlling its immediate availability and leaching.

PMID- 19380195
TI  - Sorption of Cr(VI) by Amberlite XAD-7 resin impregnated with brilliant green and
      its determination by quercetin as a selective spectrophotometric reagent.
AB  - A new chelating polymeric sorbent as an extractant-impregnated resin (EIR) has
      been developed using brilliant green (BG) and Amberlite XAD-7 resin. The BG
      impregnated resin showed superior binding affinity for Cr(VI) in the presence of
      many co-existing ions and no considerable interference was observed. The
      influence of various physicochemical parameters on the recovery of Cr(VI) were
      optimized by both static and dynamic methods. The Langmuir adsorption isotherm
      gave a satisfactory fit of the equilibrium data. The kinetic studies performed
      for Cr(VI) sorption revealed that <45 min was sufficient for reaching equilibrium
      metal ion sorption. A preconcentration factor of 100 was found for the column
      mode extraction. The spectrophotometric determination of eluted Cr(VI) was
      carried out using quercetin as a selective reagent. The calibration graphs were
      linear in the range 5.0 x 10(-8) to 4.0 x 10(-7)M with a detection limit of 8 x
      10(-9)M. The proposed method has been successfully employed for the analysis of
      natural water. The recoveries for the Cr(VI) amounts spiked to the samples were
      >93%, which confirmed accuracy of the measurements.

PMID- 19380197
TI  - Template-free fabrication of hierarchically flower-like tungsten trioxide
      assemblies with enhanced visible-light-driven photocatalytic activity.
AB  - Hierarchically flower-like tungsten trioxide assemblies were fabricated on a
      large scale by a simple hydrothermal treatment of sodium tungstate in aqueous
      solution of nitric acid. The as-prepared samples were characterized by X-ray
      diffraction, scanning electron microscopy and N(2) adsorption-desorption
      measurements. The photocatalytic activity was evaluated by photocatalytic
      decolorization of rhodamine B aqueous solution under visible-light irradiation.
      It was found that the three-dimensional tungsten trioxide assemblies were
      constructed from two-dimensional layers, which were further composed of a large
      number of interconnected lathy nanoplates with different sizes. Such flower-like
      assemblies exhibited hierarchically porous structure and higher visible-light
      photocatalytic activity than the samples without such hierarchical structures due
      to their specific hierarchical pores that served as the transport paths for light
      and reactants. After five recycles for the photodegradation of RhB, the catalyst
      did not exhibit any great loss in activity, confirming hierarchically flower-like
      tungsten trioxide was stability and not photocorroded. This study may provide new
      insight into environmentally benign preparation and design of novel
      photocatalytic materials and enhancement of photocatalytic activity.

PMID- 19380196
TI  - Cloud point extraction and flame atomic absorption spectrometric determination of
      cadmium(II), lead(II), palladium(II) and silver(I) in environmental samples.
AB  - The phase-separation phenomenon of non-ionic surfactants occurring in aqueous
      solution was used for the extraction of cadmium(II), lead(II), palladium(II) and
      silver(I). The analytical procedure involved the formation of understudy metals
      complex with bis((1H-benzo [d] imidazol-2yl)ethyl) sulfane (BIES), and
      quantitatively extracted to the phase rich in octylphenoxypolyethoxyethanol
      (Triton X-114) after centrifugation. Methanol acidified with 1molL(-1) HNO(3) was
      added to the surfactant-rich phase prior to its analysis by flame atomic
      absorption spectrometry (FAAS). The concentration of BIES, pH and amount of
      surfactant (Triton X-114) was optimized. At optimum conditions, the detection
      limits of (3 sdb/m) of 1.4, 2.8, 1.6 and 1.4 ng mL(-1) for Cd(2+), Pb(2+), Pd(2+)
      and Ag(+) along with preconcentration factors of 30 and enrichment factors of 48,
      39, 32 and 42 for Cd(2+), Pb(2+), Pd(2+) and Ag(+), respectively, were obtained.
      The proposed cloud point extraction has been successfully applied for the
      determination of metal ions in real samples with complicated matrix such as
      radiology waste, vegetable, blood and urine samples.

PMID- 19380198
TI  - Dechlorination reaction of hexachlorobenzene with calcium oxide at 300-400
      degrees C.
AB  - Hexachlorobenzene (HCB) was thermally treated with calcium oxide (CaO) at 300-400
      degrees C. Analyses of chloride ions and residual HCB confirmed that a
      dechlorination reaction had occurred. The dechlorination mechanism was
      investigated with a series of analytical methods including X-ray fluorescence
      (XRF), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron
      spectroscopy (XPS). The final products detected were CaCO(3) by XRD and Raman
      spectroscopy, amorphous carbon by Raman spectroscopy, and CaCl(2) by XPS. The
      newly produced species of CaCO(3) and amorphous carbon were thought to be the
      ultimate fate of the C element of HCB. After identification of the final
      dechlorination products, we can conclude that the reaction of HCB with CaO at 300
      400 degrees C is through a dechlorination/polymerization pathway, which is
      induced by electron transfer. An overall reaction formula for HCB reaction with
      CaO was proposed and was energetically quite favorable. The results are helpful
      for the further comprehension of the reaction mechanism for thermal
      dechlorination of PCDD/Fs in CaO rich matrices.

PMID- 19380199
TI  - Accumulation and tolerance characteristics of cadmium in a potential
      hyperaccumulator--Lonicera japonica Thunb.
AB  - Phytoremediation using hyperaccumulators is a promising technique of removing
      soil pollutants. In the study, growth responses, cadmium (Cd) accumulation
      capability and physiological mechanisms of Lonicera japonica Thunb. under Cd
      stress were investigated. Exposed to 5 and 10 mg L(-1) Cd, the plants did not
      show any visual symptoms, furthermore, the height, dry biomass of leaves, roots
      and total and the chlorophyll (CHL) content were obtained different grade
      increase. When the concentration of Cd was up to 50 mg L(-1), the height, dry
      biomass of leaves and roots had not significant differences compared with the
      control. The indexes of tolerance (IT) were all above 0.8. The maintenance of
      high superoxide dismutase (SOD) and catalase (CAT) activities was observed along
      with the increased Cd concentration, suggesting strong internal detoxification
      mechanisms inside plant cells. After 21 days exposure to 25 mg L(-1) Cd, stem and
      shoot Cd concentrations reached 344.49+/-0.71 and 286.12+/-9.38 microg g(-1) DW,
      respectively and the plant had higher bioaccumulation coefficient (BC) and
      translocation factor (TF). According to these results, it was shown L. japonica
      had strong tolerance and accumulation capability to Cd, therefore it is a
      potential Cd-hyperaccumulator.

PMID- 19380200
TI  - Biosorptive removal of mercury(II) from aqueous solution using lichen
      (Xanthoparmelia conspersa) biomass: kinetic and equilibrium studies.
AB  - The potential use of the lichen biomass (Xanthoparmelia conspersa) to remove
      mercury(II) ions from aqueous solution by biosorption was evaluated using the
      batch method. Effects of pH, contact time, biomass concentration and temperature
      on the removal of Hg(II) ions were studied. The Langmuir isotherm models defined
      the equilibrium data precisely compared to Freundlich model and the maximum
      biosorption capacity obtained was 82.8 mg g(-1). From the D-R isotherm model, the
      mean free energy was calculated as 9.5 kJ mol(-1). It shows that the biosorption
      of Hg(II) ions onto X. conspersa biomass was taken place by chemical ion
      exchange. Experimental data were also performed to the pseudo-first-order and
      pseudo-second-order kinetic models. The results indicated that the biosorption of
      Hg(II) on the lichen biomass followed well the second-order kinetics.
      Thermodynamic parameters, DeltaG(o), DeltaH(o) and DeltaS(o) indicated the Hg(II)
      sorption to be exothermic and spontaneous with decreased randomness at the solid
      solution interface. Furthermore, the lichen biomass could be regenerated using 1M
      HCl, with up to 85% recovery, which allowed the reuse of the biomass in ten
      biosorption-desorption cycles without any considerable loss of biosorptive
      removal capacity.

PMID- 19380201
TI  - Mineralogy and heavy metal leachability of magnetic fractions separated from some
      Chinese coal fly ashes.
AB  - Magnetic fractions (MFs) in fly ashes from eight coal-burning power plants were
      extracted by magnetic separation procedure. Their mineralogy and potential
      leachability of heavy metals were analyzed using rock magnetism, X-ray
      diffraction (XRD), scanning electron microscopy equipped with energy-dispersive X
      ray spectroscopy (SEM/EDX) and leaching procedures (toxicity characteristics
      leaching procedure by the United States Environmental Protection Agency, TCLP,
      and gastric juice simulation test, GJST). Results show that the MFs in the fly
      ashes range between 2.2 and 16.3wt%, and are generally composed of magnetite,
      hematite, quartz and mullite. Thermomagnetic analysis and SEM/EDX indicate that
      the main magnetic carrier magnetite is substituted with small amounts of impure
      ions, and its structures are featured by rough, dendritic and granular iron
      spherules. The MFs are found to be rich in Fe, Mn, Cr, Cu, Cd and Pb. Compared
      with the non-magnetic fractions (NMFs), the MFs have about 5 times higher iron,
      and 1.6 times higher Mn, Cr, Cu and Cd concentrations. The TCLP test shows that
      the TCLP-extractable Cr, Cu, and Pb concentrations in the MFs are higher than
      those in the NMFs, while the TCLP-extractable Cd concentration in the MFs and
      NMFs is below the detection limit (<0.1mg/L). The GJST-extractable Cd, Cr, Cu,
      and Pb concentrations in the MFs are higher those in the NMFs. No significant
      difference in the leachability ratio of Cr, Cu and Pb with TCLP and GJST is found
      in the MFs and NMFs. However, the GJST test showed that Pb has higher
      leachability in MFs than that in NMFs. The leachability ratio of heavy metals has
      an order of Cu>Cr>Pb>Cd. The heavy metals of fly ashes have a great potential to
      be released into the environment under acid environment.

PMID- 19380202
TI  - Random ionic mobility on blended cements exposed to aggressive environments.
AB  - It is known that the partial replacement of cement by pozzolanic admixtures
      generally leads to modifications in the diffusion rates of harmful ions. Recent
      research has centred on obtaining new pozzolanic materials from industrial waste
      and industrial by-products and on the way that such products can influence the
      performance of blended cements. This paper reports the behaviour of cements
      blended with calcined paper sludge (CPS) admixtures under exposure to two
      different field conditions: sea water and cyclic changes in temperature and
      humidity. Cement mortars were prepared with 0% and 10% paper sludge calcined at
      700 degrees C. The penetration of ions within the microstructure of cement
      matrices was studied using X-ray diffraction (XRD) and scanning electron
      microscopy equipped with an energy dispersive X-ray analyser (SEM/EDX) analytical
      techniques. The results show that ionic mobility varies substantially according
      to the type of exposure and the presence of the calcined paper sludge. The
      incorporation of 10% CPS is shown to assist the retention and diffusion of the
      ions.

PMID- 19380203
TI  - Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO)
      compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee
      osteoarthritis.
AB  - While topical non-steroidal anti-inflammatory drugs are considered safe, their
      long-term efficacy for osteoarthritis has been suspect. We conducted a 12-week,
      double-blind, double-dummy, randomized controlled trial of topical diclofenac
      (TDiclo) in a vehicle solution containing dimethyl sulfoxide (DMSO) in 775
      subjects with radiologically confirmed, symptomatic primary osteoarthritis of the
      knee. This 5-arm study compared TDiclo with a placebo solution, the DMSO vehicle,
      oral diclofenac (ODiclo) and the combination of TDiclo+ODiclo for relieving the
      signs and symptoms of knee osteoarthritis. Subjects applied study solution, 40
      drops four times daily, and took one study tablet daily for 12 weeks. Co-primary
      efficacy variables were WOMAC pain and physical function and a patient overall
      health assessment. Secondary variables were WOMAC stiffness and patient global
      assessment (PGA) of the knee osteoarthritis. TDiclo was superior to placebo for
      pain (-6.0 vs. -4.7, P=0.015), physical function (-15.8 vs. -12.3, P=0.034),
      overall health (-0.95 vs. -0.37, P<0.0001), and PGA (-1.36 vs. -1.01, P=0.016),
      and was superior to DMSO vehicle for all efficacy variables. No significant
      difference was observed between DMSO vehicle and placebo or between TDiclo and
      ODiclo. The commonest adverse event associated with TDiclo was dry skin (18.2%).
      Fewer digestive system and laboratory abnormalities were observed with TDiclo
      than with ODiclo. Addition of TDiclo to ODiclo did not increase the incidence of
      systemic adverse events. TDiclo in DMSO vehicle is an effective treatment option
      for knee osteoarthritis with efficacy similar to, but tolerability better than
      ODiclo. DMSO vehicle was no more efficacious than placebo.

PMID- 19380204
TI  - Local work function control of indium tin oxide by micro-contact printing for
      electroluminescent devices.
AB  - We demonstrate here that light emission of an electroluminescent (EL) device was
      enhanced on chemically modified ITO areas over a patterned ITO anode with a self
      assembled monolayer (SAM) of 4-chlorophenylphosphoryl dichloride
      (ClC(6)H(4)OPOCl(2): CPPDC) prepared by micro-contact printing (mu-CP). The EL
      device was fabricated by vapor-depositing a hole transport layer, a light
      emitting and electron transport layer, and a C(6)H(5)COOLi/Al bilayer cathode on
      the patterned ITO anode. The enhanced light emission under lower drive voltages
      on the modified areas can be interpreted by the increase in the work function of
      the ITO covered with the SAM measured with a Kelvin probe force microscope (KPFM)
      and thus the decrease in the hole injection barrier height. In addition, we could
      demonstrate the much smaller pattern images than the previously reported ones [F.
      Nuesch, Y. Li, L.J. Rothberg, Appl. Phys. Lett. 75 (1999) 1799] by the use of ink
      pads.

PMID- 19380205
TI  - Viability assays of intra-erythrocytic organisms using fluorescent dyes.
AB  - Three intra-erythrocytic tick fever organisms of cattle (Babesia bovis, Babesia
      bigemina and Anaplasma centrale) were subjected to a range of stressors,
      including heat, storage over time, specific chemotherapy and cryopreservation.
      Various stains, both alone and in combination, were used in an attempt to assess
      viability of these organisms before and after the stressors were applied.
      Carboxyfluorescein diacetate succinimidyl ester (CFSE) stained live Babesia spp.
      very well while fluorescein diacetate (FDA) stained A. centrale successfully.
      Propidium iodide (PI) and ethidium-homodimer-1 (Eth-D) were used as counter
      stains to identify dead organisms. Stain combinations allowed differentiation
      between living and dead Babesia organisms after exposure to heat and after
      chemotherapy. PI and Eth-D as counter stains were of little value after
      deglycerolisation of cryopreserved organisms. Possible reasons for this limited
      success in determining death or viability of tick fever organisms after some
      treatments include the impermeability of red blood cells to PI and Eth-D counter
      stains or the loss of live and/or dead organisms during sample processing.

PMID- 19380206
TI  - Serological detection of anti-Trichinella antibodies in wild foxes and
      experimentally infected farmed foxes in Norway.
AB  - Trichinella surveillance in wildlife has relied on the detection of muscle larvae
      using digestion techniques. Serology has been proposed as more suitable for large
      scale epidemiological studies in wildlife. In this study, 328 individual sera
      from wild red foxes and 16 sera from experimentally infected farmed foxes were
      serologically tested with both excretory/secretory antigen (E/S) and the
      synthetic beta-tyvelose glycan antigen, in indirect ELISA tests. The wild red
      foxes (Vulpes vulpes) had previously been examined for muscle larvae, using
      muscle digestion, whilst the experimentally infected farmed foxes were inoculated
      per os with either a low dose, 500 larvae, or a high dose, 10,000 of Trichinella
      nativa muscle larvae. Western blot (WB) was carried out on all seropositive
      samples using crude larval antigen. The present study found both beta-tyvelose
      and E/S antigen suited for the detection of antibodies to Trichinella spp., and
      T. nativa in particular, in foxes. Both ELISA antigens performed well, although,
      the E/S antigen was superior to the beta-tyvelose antigen, with sera that had
      been stored at -20 degrees C for more than 10 years. Neither antigen, however,
      detected all of the samples proven seropositive by WB: E/S detected 21 of the 27
      wild red fox sera positive by WB; beta-tyvelose detected 22 positive sera; and in
      total 24 of the 27 positive WB sera were identified using both antigens. Serology
      alone, without WB or muscle digestion, led to a two- to threefold higher
      seroprevalence estimate, respectively. The use of E/S antigen in conjunction with
      the WB was the method of choice for the screening of wild red fox populations for
      Trichinella. Antibody persistence to T. nativa was short in the low dose group
      where antibody levels were not different from background by 32 wpi. In total,
      7.3% (24/328) of the wild red fox population had antibodies to Trichinella on
      ELISA and WB. Antibodies were identified in foxes from a further two regions in
      Norway compared to the original muscle digestion results.

PMID- 19380207
TI  - Specific medical intervention for diabetic retinopathy.
AB  - Diabetes is a global epidemic and the major complication of diabetes in the eye,
      diabetic retinopathy, is a leading cause of blindness in several countries.
      Medical and surgical interventions have been formally investigated for over half
      a century, but currently only surgical interventions are the standard of care and
      these treatments are not without significant side effects. Several clinical
      trials have investigated a protein kinase C (PKC) beta inhibitor as a possible
      medical intervention for diabetic retinopathy. Though successful in animal
      studies and smaller clinical studies, the drug showed only marginal success in
      clinical trials. It is likely that the clinical trials failed for two reasons:
      (1) enrolling patients with too severe a disease state at baseline and (2)
      utilizing conventional outcome measures that essentially require severe disease
      states at baseline for evaluation after a standard follow-up time. Additional
      clinical trials that enroll patients with earlier stages of diabetic retinopathy
      and/or utilizing more sensitive surrogate outcomes over a longer follow-up would
      likely show clinical success of PKC-beta inhibition for the treatment of the
      diabetic retinopathy.

PMID- 19380208
TI  - Numb--from flies to humans.
AB  - Numb carries the distinction of being the first molecule discovered to influence
      cell fate by being asymmetrically segregated during cell division. Originally
      identified from studies in Drosophila, further work has since demonstrated the
      importance of Numb in mammalian and, in particular, human systems, from diverse
      fields such as developmental neurobiology to cancer biology and neurodegenerative
      disease. This review surveys the body of knowledge concerning Numb, and discusses
      the relevance of Numb to human biology and disease.

PMID- 19380209
TI  - Radiation effects analysis in a group of interventional radiologists using
      biological and physical dosimetry methods.
AB  - Interventional radiologists and staff members are frequently exposed to
      protracted and fractionated low doses of ionizing radiation, which extend during
      all their professional activities. These exposures can derive, due to the effects
      of direct and scattered radiation, in deterministic effects (radiodermitis, aged
      skin, cataracts, telangiectasia in nasal region, vasocellular epitelioms, hands
      depilation) and/or stochastic ones (cancer incidence). A methodology has been
      proposed for estimating the radiation risk or detriment from a group of six
      exposed interventional radiologists of the Hospital Universitario La Fe
      (Valencia, Spain), which had developed general exposition symptoms attributable
      to deterministic effects of ionizing radiation. Equivalent doses have been
      periodically registered using TLD's and wrist dosimeters, H(p)(10) and
      H(p)(0.07), respectively, and estimated through the observation of translocations
      in lymphocytes of peripheral blood (biological methods), by extrapolating the
      yield of translocations to their respective dose-effect curves. The software
      RADRISK has been applied for estimating radiation risks in these occupational
      radiation exposures. This software is based on transport models from
      epidemiological studies of population exposed to external sources of ionizing
      radiation, such as Hiroshima and Nagasaki atomic bomb survivors [UNSCEAR, Sources
      and effects of ionizing radiation: 2006 report to the general assembly, with
      scientific annexes. New York: United Nations; 2006]. The minimum and maximum
      average excess ratio for skin cancer has been, using wrist physical doses, of
      [1.03x10(-3), 5.06x10(-2)], concluding that there is not an increased risk of
      skin cancer incidence. The minimum and maximum average excess ratio for leukemia
      has been, using TLD physical doses, of [7.84x10(-2), 3.36x10(-1)], and using
      biological doses, of [1.40x10(-1), 1.51], which is considerably higher than
      incidence rates, showing an excess radio-induced risk of leukemia in the group
      under study. Finally, the maximum radiological detriment in the group, evaluated
      as the total number of radio-induced cancers using physical dosimetry, has been
      of 2.18/1000 person-year (skin and leukemia), and using biological dosimetry of
      9.20/1000 PY (leukemia). As a conclusion, this study has provided an assessment
      of the non-deterministic effects (rate of radio-induced cancer incidence)
      attributable to the group under study due to their professional activity.

PMID- 19380210
TI  - A method to quantify and compare clinicians' assessments of patient understanding
      during counseling of standardized patients.
AB  - OBJECTIVE: To introduce a method for quantifying clinicians' use of assessment of
      understanding (AU) questions, and to examine medicine residents' AU usage during
      counseling of standardized patients about prostate or breast cancer screening.
      METHODS: Explicit-criteria abstraction was done on 86 transcripts, using a data
      dictionary for 4 AU types. We also developed a procedure for estimating the
      "load" of informational content for which the clinician has not yet assessed
      understanding. RESULTS: Duplicate abstraction revealed reliability kappa=0.96.
      Definite criteria for at least one AU were found in 68/86 transcripts (79%). Of
      these, 2 transcripts contained a request for a teach-back ("what is your
      understanding of this?"), 2 contained an open-ended AU, 46 (54%) contained only a
      close-ended AU, and 18 (21%) only contained an "OK?" question. The load
      calculation identified long stretches of conversation without an AU. CONCLUSION:
      Many residents' transcripts lacked AUs, and included AUs were often ineffectively
      phrased or inefficiently timed. Many patients may not understand clinicians, and
      many clinicians may be unaware of patients' confusion. PRACTICE IMPLICATIONS:
      Effective AU usage is important enough to be encouraged by training programs and
      targeted by population-scale quality improvement programs. This quantitative
      method should be useful in population-scale measurement of AU usage.

PMID- 19380211
TI  - Attentional capture and trait anxiety: evidence from inhibition of return.
AB  - Attentional biases regarding attentional capture by threat-related stimuli in
      anxious people were investigated by using a standard spatial cueing procedure
      suitable to measure inhibition of return (IOR). In two experiments, participants
      categorized the emotional valence of either emotional (positive and negative
      words) or non-emotional (neutral words in both experiments and sets of 'xxx' in
      Experiment 1) targets that were preceded by a peripheral non-predictive cue. The
      typical IOR effect (slower responses for words presented at previously cued
      locations) was observed for non-emotional and positive stimuli, with similar
      results being observed for both low and high trait anxiety groups. For negative
      stimuli, however, the high trait anxiety group did not show the IOR effect, while
      it was present in the low trait anxiety group. This general pattern of results
      suggests that, in individual with high trait anxiety, threatening stimuli can
      capture attention at the locations whether attentional capture is hindered by
      other cognitive effects such as IOR.

PMID- 19380212
TI  - Outcome of epilepsy surgery in patients investigated with subdural electrodes.
AB  - Invasive intracranial electrodes (IE) are an important part of the work-up in
      many patients being considered for epilepsy surgery. Because IE are usually
      reserved for cases where seizure localization is ambiguous, one might expect that
      the eventual outcome of epilepsy surgery in these patients would be worse than in
      patients who did not require IE as part of their work-up. The purpose of this
      study was to specifically examine those patients who underwent insertion of
      subdural electrodes, to determine how many of these patients eventually underwent
      resective surgery of any type and to assess the eventual outcome. All cases
      admitted for subdural electrodes between January 2000 and June 2005 were
      reviewed. Surgical outcomes were reported using the Engel classification and a
      multivariate analysis was used to determine which factors were associated with
      successful surgery. 177 IE implantations were performed in 172 patients. Of
      these, 130 patients went on to have surgery. In the 113 of the 130 surgical
      patients in whom 1-year follow-up was available, 47% were seizure free at 1 year.
      Age was a major predictor of outcome with only 21% of patients over age 40
      becoming seizure free with surgery compared to 58% in patients aged under 40
      years (p=0.0004). Other predictors of an Engel I outcome included having a
      temporal lobectomy or supplementary motor area resection. Good results from
      eventual resective surgery can be achieved in patients needing invasive
      recordings. Younger patients with temporal lobe epilepsy seem to have the highest
      likelihood of seizure freedom.

PMID- 19380213
TI  - Resistance to tetracycline, erythromycin and clindamycin in Streptococcus suis
      serotype 2 in Hong Kong.

PMID- 19380214
TI  - Multiple-dose pharmacokinetics of telithromycin in peripheral soft tissues.
AB  - Based on clinicians' expectations of high concentrations of telithromycin (TEL)
      in tissues, combined with its excellent in vitro antimicrobial characteristics,
      TEL is casually considered as a potential therapeutic option for the therapy of
      minor cases of soft tissue or bite-wound infections. To clarify this clinically
      important issue, the present investigation was carried out to measure the
      pharmacokinetic profile of TEL in the interstitial space fluid (ISF) of skeletal
      muscle and subcutaneous adipose tissue by means of the microdialysis technique in
      10 healthy subjects following repetitive daily doses of 800 mg TEL. These data
      were compared with free concentrations of TEL determined in plasma. External
      controls for the present examination were the use of historic, single-dose data
      collected by our study group utilising identical methods and the same trial
      subjects. Despite an increase in the median half-life from ca. 3 h after a single
      dose to ca. 10h at steady-state conditions in all compartments, accumulation of
      TEL in ISF of soft tissues and plasma was clinically non-relevant. Median free
      peak concentrations in plasma, skeletal muscle and subcutis were 0.52, 0.13 and
      0.19 mg/L, respectively. The median ratios of the tissue to plasma free areas
      under the concentration-time curves from 0 to 24 h (fAUC(0-24) tissue/fAUC(0-24)
      plasma) were 0.27 and 0.58 for muscle and subcutis, respectively (P>0.05). The
      present multiple-dose investigation of TEL is in line with a previous single-dose
      study confirming that TEL 800 mg/day may not be optimally effective in the
      therapy of soft tissue infections.

PMID- 19380215
TI  - Solution properties and vesicle formation of rhamnolipid biosurfactants produced
      by Pseudomonas aeruginosa SP4.
AB  - A biosurfactant produced by Pseudomonas aeruginosa strain SP4 was previously
      reported as a mixture of 11 types of rhamnolipid compounds. Among them, the major
      component in the biosurfactant was characterized as l-rhamnosyl-3-hydroxydecanoyl
      3-hydroxydecanoate, or monorhamnolipid (Rha-C(10)-C(10)). In this present study,
      solution properties of the biosurfactant were investigated in a phosphate-buffer
      saline (PBS) solution (pH 7.4) by using surface tension, turbidity, electrical
      conductivity, and dynamic light scattering (DLS) measurements. It was found that
      spherical biosurfactant vesicles of various sizes (ranging from 50 to larger than
      250 nm) were spontaneously formed at a biosurfactant concentration greater than
      its critical micelle concentration (CMC), which was 200mg/l. The encapsulation
      efficiency (E%) of the biosurfactant vesicles was preliminarily studied by using
      Sudan III, a water-insoluble dye, as a model hydrophobic substance. The obtained
      results showed that the vesicle formed in the PBS solution at a biosurfactant
      concentration of 1280 mg/l could entrap about 10% of the initial hydrophobic dye
      concentration. The effects of salt and alcohol on the vesicle formation of the
      biosurfactant and its encapsulation efficiency were also observed by using sodium
      chloride (NaCl) and ethanol (C(2)H(5)OH), respectively. In the presence of either
      NaCl or C(2)H(5)OH, the vesicle size was reduced from larger than 250 nm to 50
      250 nm. The encapsulation efficiency of the biosurfactant vesicle was slightly
      influenced by the addition of NaCl, but was significantly increased, up to nearly
      30%, in the presence of C(2)H(5)OH.

PMID- 19380216
TI  - The interactions between phosphatidylglycerol and phosphatidylethanolamines in
      model bacterial membranes: the effect of the acyl chain length and saturation.
AB  - In this work the Langmuir monolayer technique was applied to study the
      interactions between phosphatidylglycerol (PG) and phosphatidylethanolamines
      (PEs). Since the technique of monomolecular layers is useful method of modeling
      of biomembranes and the investigated lipids are the major components of Gram
      negative bacteria bilayers the results obtained were discussed in the context of
      the properties of bacterial membranes. To investigate the influence of the
      phosphatidylethanolamine acyl chain structure on its miscibility and interactions
      with dipalmitoylphosphatidylglycerol (DPPG) the chosen phosphatidylethanolamines
      differed both in the length (dipalmitoylphosphatidylethanolamine (DPPE),
      distearoylphosphatidylethanolamine (DSPE)), and saturation
      (dioleoylphosphatidylethanolamine (DOPE)) of the hydrocarbon chains. The obtained
      results prove non ideal behaviour of all of the mixed systems studied. It was
      found that in monolayers between DPPG and phosphatidylethanolamines with
      saturated acyl chains (DPPE, DSPE) strong attractions resulting from the
      formation of hydrogen bonds exist. These attractions are the strongest for
      equimolar mixtures indicating that PG and PE molecules form the "complexes" of
      1:1 proportion. In DOPE/DPPG mixed system the distance between phospholipids is
      larger, due to the presence of the cis double bonds in the acyl chains of DOPE
      molecule, which makes the formation of the hydrogen bonds more difficult. The
      interactions between molecules, the molecular packing and the stability of the
      investigated mixed systems were thoroughly discussed from the point of view of
      the effect of polar head and PEs acyl chain structure. Basing on the obtained
      results it was suggested that PG molecules play in bacterial membranes similar
      role as cholesterol in mammalian bilayers.

PMID- 19380217
TI  - A cross-over response to sequential use of sunitinib after sorafenib in a patient
      with metastatic renal cell carcinoma.

PMID- 19380218
TI  - Inhibitory effect of methanol extract of Rosa damascena Mill. flowers on alpha
      glucosidase activity and postprandial hyperglycemia in normal and diabetic rats.
AB  - The effect of a methanol extract of Rosa damascena Mill. flowers was studied, in
      comparison to the alpha-glucosidase inhibitor acarbose, in normal and diabetic
      rats. The inhibition mode of this extract was examined by measuring enzyme
      activity in different concentrations of substrate for Lineweaver-Burk plot
      analysis. The results show that Rosa damascena extract has an intensive
      inhibitory effect on alpha-glucosidase. Its inhibition was found to be
      noncompetitive. Oral administration of this plant extract (100 to 1000 mg/kg body
      wt.) significantly decreased blood glucose after maltose loading in normal and
      diabetic rats in a dose-dependent manner. These results suggest that Rosa
      damascena might exert an anti-diabetic effect by suppressing carbohydrate
      absorption from the intestine and can reduce the postprandial glucose level.

PMID- 19380220
TI  - Effect of commercial mineral-based additives on composting and compost quality.
AB  - The effectiveness of two commercial additives meant to improve the composting
      process was studied in a laboratory-scale experiment. Improver A (sulphates and
      oxides of iron, magnesium, manganese, and zinc mixed with clay) and B (mixture of
      calcium hydroxide, peroxide, and oxide) were added to source-separated
      biowaste:peat mixture (1:1, v/v) in proportions recommended by the producers. The
      composting process (T, emissions of CO(2), NH(3), and CH(4)) and the quality of
      the compost (pH, conductivity, C/N ratio, water-soluble NH(4)-N and NO(3)-N,
      water- and NaOH-soluble low-weight carboxylic acids, nutrients, heavy metals and
      phytotoxicity to Lepidium sarivum) were monitored during one year. Compared with
      the control, the addition of improver B increased pH by two units, led to an
      earlier elimination of water-soluble ammonia, an increase in nitrates, a 10-fold
      increase in concentrations of acetic acid, and shortened phytotoxicity period by
      half; as negative aspect it led to volatilization of ammonia. The addition of
      improver A led to a longer thermophilic stage by one week and lower
      concentrations of low-weight carboxylic acids (both water- and NaOH-extractable)
      with formic and acetic of similar amounts, however, most of the aspects claimed
      by the improver's producer were not confirmed in this trial.

PMID- 19380219
TI  - Associations of maternal prenatal dietary intake of n-3 and n-6 fatty acids with
      maternal and umbilical cord blood levels.
AB  - Maternal n-3 and n-6 polyunsaturated fatty acid (PUFA) status may influence birth
      outcomes and child health. We assessed second trimester maternal diet with food
      frequency questionnaires (FFQs) (n=1666), mid-pregnancy maternal erythrocyte PUFA
      concentrations (n=1550), and umbilical cord plasma PUFA concentrations (n=449).
      Mean (SD) maternal intake of total n-3 PUFA was 1.17 g/d (0.43), docosahexaenoic
      and eicosapentaenoic acids (DHA+EPA) 0.16 g/d (0.17), and total n-6 PUFA 12.25
      g/d (3.25). Mean maternal erythrocyte and cord plasma PUFA concentrations were
      7.0% and 5.2% (total n-3), 5.0% and 4.6% (DHA+EPA), and 27.9% and 31.4% (total n
      6). Mid-pregnancy diet-blood and blood-blood correlations were strongest for
      DHA+EPA (r=0.38 for diet with maternal blood, r=0.34 for diet with cord blood,
      r=0.36 for maternal blood with cord blood), and less strong for n-6 PUFA. The FFQ
      is a reliable measure of elongated PUFA intake, although inter-individual
      variation is present.

PMID- 19380221
TI  - Hazardous healthcare waste management in the Kingdom of Bahrain.
AB  - Hazardous healthcare waste has become an environmental concern for many
      developing countries including the Kingdom of Bahrain. There have been several
      significant obstacles facing the Kingdom in dealing with this issue including;
      limited documentation regarding generation, handling, management, and disposal of
      waste. This in turn hinders efforts to plan better healthcare waste management.
      In this paper, hazardous waste management status in the Kingdom has been
      investigated through an extensive survey carried out on selected public and
      private healthcare premises. Hazardous waste management practices including:
      waste generation, segregation, storage, collection, transportation, treatment,
      and disposal were determined. The results of this study along with key findings
      are discussed and summarized. In addition; several effective recommendations and
      improvements of hazardous waste management are suggested.

PMID- 19380222
TI  - Integrated microring resonator biosensors for monitoring cell growth and
      detection of toxic chemicals in water.
AB  - Integrated microring resonators fabricated on silicon wafers were used as signal
      transducers to detect alterations in physical traits of attached live mammalian
      cells. Cell adhesion and growth events could be monitored by the shift in
      resonance frequency of the microring resonator. Toxic chemical-induced changes in
      cell motility were rapidly detected based on variations in the fluctuation of
      resonance frequency. Microring resonators modified with an endothelial cell line
      (MS1) adhered onto its surface were used to detect the presence of two toxic
      chemicals, viz. sodium pentachlorophenate and Aldicarb at concentrations above
      the military exposure guideline levels within a duration of 1 h.

PMID- 19380223
TI  - Fabrication and testing of polyimide-based microelectrode arrays for cortical
      mapping of evoked potentials.
AB  - Modern microfabrication techniques make it possible to develop microelectrode
      arrays that may be utilized not only in neurophysiological research but also in
      the clinic, e.g. in neurosurgery and as elements of neural prostheses. The aim of
      this study was to test whether a flexible microelectrode array is suitable for
      recording cortical surface field potentials in rats. Polyimide-based
      microelectrode arrays were fabricated by utilizing microfabrication techniques
      e.g. photolithography and magnetron sputter deposition. The present
      microelectrode array consists of eight platinum microelectrodes (round-shaped, O:
      200 microm), transmission lines and connector pads sandwiched between two thin
      layers of biocompatible polyimide. The microelectrode arrays were
      electrochemically characterized by impedance spectroscopy in physiological saline
      solution and successfully tested in vivo by conducting acute and chronic
      measurements of evoked potentials on the surface of rat cortex. The arrays proved
      excellent flexibility and mechanical strength during handling and implantation
      onto the surface of cortex. The excellent electrochemical characteristics and
      stable in vivo recordings with high spatiotemporal resolution highlight the
      potential of these arrays. The fabrication protocol described here allows
      implementation of several other neural interfaces with different layouts,
      material selections or target areas either for recording or stimulation purposes.

PMID- 19380224
TI  - Membrane fouling control and enhanced phosphorus removal in an aerated submerged
      membrane bioreactor using modified green bioflocculant.
AB  - This study aims at developing a modified green bioflocculant (GBF) for membrane
      fouling control and enhanced phosphorus removal in a conventional aerated
      submerged membrane bioreactor (SMBR) to treat a high strength domestic wastewater
      (primary sewage treated effluent) for reuse. The GBF was evaluated based on long
      term operation of a lab-scale SMBR. These results showed that SMBR system could
      achieve nearly zero membrane fouling at a very low dose of GBF addition (500
      mg/day) with less backwash frequency (2 times/day with 2-min duration). The
      transmembrane pressure only increased by 2.5 kPa after 70 days of operation. The
      SMBR could also remove more than 95% and 99.5% dissolved organic carbon and total
      phosphorus, respectively. From the respiration tests, it was evident that GBF not
      only had no negative impact on biomass but also led to high oxygen uptake rate
      (OUR) (>30 mg O(2)/L h) and stable specific oxygen uptake rate (SOUR). These
      results also indicated that GBF had no effect on nitrogen removal and
      nitrification process.

PMID- 19380225
TI  - Rapid identification of improved protein ligands using peptoid microarrays.
AB  - A rapid array-based protocol is presented by which a modest affinity protein
      binding small molecule can be appended to a library of peptoids via click
      chemistry. The array can then be screened for improved ligands that exhibit a
      higher affinity for the protein target.

PMID- 19380226
TI  - Efficient syntheses of chiral myo-inositol derivatives--key intermediates in
      glycosylphosphatidylinositol (GPI) syntheses.
AB  - A facile and effective method was developed for large-scale syntheses of myo
      inositol derivatives with the 1,2,6-O-positions differentiated from each other
      and from other positions as well. The syntheses started from methyl alpha-D
      glucopyranoside, and the key steps are Ferrier rearrangement and a series of
      other regioselective and stereoselective reactions. The target compounds are key
      intermediates in the synthesis of GPIs.

PMID- 19380228
TI  - Rare genetic disorders in certain populations.

PMID- 19380227
TI  - Valosin-containing protein disease: inclusion body myopathy with Paget's disease
      of the bone and fronto-temporal dementia.
AB  - Mutations in valosin-containing protein (VCP) cause inclusion body myopathy (IBM)
      associated with Paget's disease of the bone (PDB) and fronto-temporal dementia
      (FTD) or IBMPFD. Although IBMPFD is a multisystem disorder, muscle weakness is
      the presenting symptom in greater than half of patients and an isolated symptom
      in 30%. Patients with the full spectrum of the disease make up only 12% of those
      affected; therefore it is important to consider and recognize IBMPFD in a
      neuromuscular clinic. The current review describes the skeletal muscle phenotype
      and common muscle histochemical features in IBMPFD. In addition to myopathic
      features; vacuolar changes and tubulofilamentous inclusions are found in a subset
      of patients. The most consistent findings are VCP, ubiquitin and TAR DNA-binding
      protein 43 (TDP-43) positive inclusions. VCP is a ubiquitously expressed
      multifunctional protein that is a member of the AAA+ (ATPase associated with
      various activities) protein family. It has been implicated in multiple cellular
      functions ranging from organelle biogenesis to protein degradation. Although the
      role of VCP in skeletal muscle is currently unknown, it is clear that VCP
      mutations lead to the accumulation of ubiquitinated inclusions and protein
      aggregates in patient tissue, transgenic animals and in vitro systems. We suggest
      that IBMPFD is novel type of protein surplus myopathy. Instead of accumulating a
      poorly degraded and aggregated mutant protein as seen in some myofibrillar and
      nemaline myopathies, VCP mutations disrupt its normal role in protein homeostasis
      resulting in the accumulation of ubiquitinated and aggregated proteins that are
      deleterious to skeletal muscle.

PMID- 19380229
TI  - Synthesis, antiplatelet and in silico evaluations of novel N-substituted
      phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides.
AB  - This paper describes the synthesis, antiplatelet and theoretical evaluations of
      10 N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides (2a-j).
      These compounds were synthesized, characterized and screened for their in vitro
      antiplatelet profile against human platelet aggregation using arachidonic acid,
      adrenaline and ADP as agonists. Among NAH derivatives 2a-j, the compounds 2a, 2c,
      2e, 2g and 2h were the most promising molecules with significant antiplatelet
      activity.

PMID- 19380230
TI  - Evaluation of all dose components in the LVR-15 reactor epithermal neutron beam
      using Fricke gel dosimeter layers.
AB  - Fricke gel dosimeters in the form of layers are suitable to reconstruct
      bidimensional distributions of the absorbed dose; in accordance with their
      chemical composition and applying suitably developed algorithms, they can provide
      dose images of the different radiation components in a BNCT field. After the
      description of the applied method, this work presents the results obtained at the
      epithermal column of the BNCT facility at the NRI in Rez (CZ). The measured dose
      distributions are shown in comparison with data taken by means of other
      dosimeters thermoluminescence dosimeters (TLDs) and with calculations carried out
      with the Monte Carlo code MCNP5. The agreement with the results obtained by means
      of the different techniques is satisfying.

PMID- 19380231
TI  - A detailed Monte Carlo accounting of radiation transport in the brain during
      BNCT.
AB  - The collision type central to BNCT is (10)B(n, alpha)(7)Li, however, other types
      of nuclear reactions also take place in the patient. In addition to the major
      elements (H, C, N, O), minor elements such as Na, Mg, P, S, Cl, K, Ca and Fe
      present in body tissues also interact in neutron collisions. Detailed accounting
      of the above not only provides a better understanding of radiation transport in
      the human body during BNCT, but such knowledge affects the design of the
      facility, as well as treatment planning, imaging and verification for a given
      BNCT agent. Of the methods of investigation currently available, only Monte Carlo
      simulation could provide the detailed accounting and breakdown of the quantities
      required. We report Monte Carlo simulation of an anthropomorphic voxel phantom,
      the VIP-Man and show how these quantities change with different (10)B
      concentrations in the tumour, the blood and the remaining tissues. The (10)B
      biodistribution has been chosen to be the variable of interest, since it is not
      accurately known, is frequently approximated and is a crucial quantity upon which
      dose calculations are based.

PMID- 19380232
TI  - Dynamic infrared imaging of cutaneous melanoma and normal skin in patients
      treated with BNCT.
AB  - We recently initiated a program aimed to investigate the suitability of dynamic
      infrared imaging for following-up nodular melanoma patients treated with BNCT.
      The reason that makes infrared imaging attractive is the fact that it constitutes
      a functional and non-invasive imaging method, providing information on the normal
      and abnormal physiologic response of the nervous and vascular systems, as well as
      the local metabolic rate and inflammatory processes that ultimately appear as
      differences in the skin temperature. An infrared camera, with a focal plane array
      of 320 x 240 uncooled ferroelectric detectors is employed, which provides a video
      stream of the infrared emission in the 7-14 microm wavelength band. A double
      blackbody is used as reference for absolute temperature calibration. After
      following a protocol for patient preparation and acclimatization, a basal study
      is performed. Subsequently, the anatomic region of interest is subjected to a
      provocation test (a cold stimulus), which induces an autonomic vasoconstriction
      reflex in normal structures, thus enhancing the thermal contrast due to the
      differences in the vasculature of the different skin regions. Radiation erythema
      reactions and melanoma nodules possess typically a faster temperature recovery
      than healthy, non-irradiated skin. However, some other non-pathological
      structures are also detectable by infrared imaging, (e.g. scars, vessels,
      arteriovenous anastomoses and injuries), thus requiring a multi-study comparison
      in order to discriminate the tumor signal. Besides the superficial nodules, which
      are readily noticeable by infrared imaging, we have detected thermal signals that
      are coincident with the location of non-palpable nodules, which are observable by
      CT and ultrasound. Diffuse regions of fast temperature recovery after a cold
      stimulus were observed between the third and sixth weeks post-BNCT, concurrent
      with the clinical manifestation of radiation erythema. The location of the
      erythematous visible and infrared regions is consistent with the 3D dosimetry
      calculations.

PMID- 19380233
TI  - Dosimetry and radiobiology at the new RA-3 reactor boron neutron capture therapy
      (BNCT) facility: application to the treatment of experimental oral cancer.
AB  - The National Atomic Energy Commission of Argentina (CNEA) constructed a novel
      thermal neutron source for use in boron neutron capture therapy (BNCT)
      applications at the RA-3 research reactor facility located in Buenos Aires. The
      aim of the present study was to perform a dosimetric characterization of the
      facility and undertake radiobiological studies of BNCT in an experimental model
      of oral cancer in the hamster cheek pouch. The free-field thermal flux was 7.1 x
      10(9) n cm(-2)s(-1) and the fast neutron flux was 2.5 x 10(6) n cm(-2)s(-1),
      indicating a very well-thermalized neutron field with negligible fast neutron
      dose. For radiobiological studies it was necessary to shield the body of the
      hamster from the neutron flux while exposing the everted cheek pouch bearing the
      tumors. To that end we developed a lithium (enriched to 95% in (6)Li) carbonate
      enclosure. Groups of tumor-bearing hamsters were submitted to BPA-BNCT, GB-10
      BNCT, (GB-10+BPA)-BNCT or beam only treatments. Normal (non-cancerized) hamsters
      were treated similarly to evaluate normal tissue radiotoxicity. The total
      physical dose delivered to tumor with the BNCT treatments ranged from 6 to 8.5
      Gy. Tumor control at 30 days ranged from 73% to 85%, with no normal tissue
      radiotoxicity. Significant but reversible mucositis in precancerous tissue
      surrounding tumors was associated to BPA-BNCT. The therapeutic success of
      different BNCT protocols in treating experimental oral cancer at this novel
      facility was unequivocally demonstrated.

PMID- 19380234
TI  - Determination of the irradiation field at the research reactor TRIGA Mainz for
      BNCT.
AB  - For the application of the BNCT for the excorporal treatment of organs at the
      TRIGA Mainz, the basic characteristics of the radiation field in the thermal
      column as beam geometry, neutron and gamma ray energies, angular distributions,
      neutron flux, as well as absorbed gamma and neutron doses must be determined in a
      reproducible way. To determine the mixed irradiation field thermoluminescence
      detectors (TLD) made of CaF(2):Tm with a newly developed energy-compensation
      filter system and LiF:Mg,Ti materials with different (6)Li concentrations and
      different thicknesses as well as thin gold foils were used.

PMID- 19380235
TI  - Monte Carlo simulation of the response of ESR dosimeters added with gadolinium
      exposed to thermal, epithermal and fast neutrons.
AB  - Monte Carlo numerical calculations of the response of alanine and ammonium
      tartrate ESR (electron spin resonance) dosimeters exposed to neutron fields with
      different energy spectra are reported. Results have been obtained for various
      gadolinium concentrations inside the dosimeters. Furthermore, in order to
      simulate the in-phantom response we have carried out calculations by varying the
      depth of the dosimeter. We have found that a large enhancement is obtained for
      thermal neutrons, because of the very high capture cross section of gadolinium to
      thermal neutrons. A good enhancement was obtained for epithermal neutrons,
      whereas the sensitivity improvement in the case of fast neutron irradiation is
      poor. Furthermore, the simulations carried out by varying the depth suggests that
      an appreciable sensitivity to thermal and epithermal neutrons could be observed
      for in-phantom measurements in the 2-3 cm depth range. These results can provide
      useful insight for future experiments with epithermal neutron beams (such as
      those used in neutron capture therapy) and for future applications in neutron
      capture therapy dosimetry.

PMID- 19380236
TI  - Is nitric oxide important in photodynamic therapy?
AB  - Photodynamic therapy (PDT) involves the use of photochemical reactions mediated
      through the interaction of photosensitizing agents, light and oxygen to destroy
      abnormal tissue. The transfer of energy from the activated photosensitizer to
      available oxygen results in the formation of toxic reactive oxygen species, such
      as singlet oxygen and free radicals, which can damage proteins, lipids, nucleic
      acids, and other cellular components. PDT is now commonly used in ophthalmology,
      dermatology and oncology however the therapeutic response to PDT exhibits
      variability, ranging from highly sensitive to extremely resistant. Over the last
      10 years it has been suggested that nitric oxide (NO) may play a role in PDT,
      with evidence that NO is produced by both tumour and normal cells in addition to
      controlling important functions in tumour progression. NO may also influence the
      outcome of cancer therapies, such as PDT. PDT induces oxidative stress, vascular
      mediated damage and leukocyte recruitment, processes all sensitive to NO. This
      review outlines the role of nitric oxide in PDT primarily focusing on vascular
      damage and how this may be modulated to improve therapeutic outcome.

PMID- 19380237
TI  - Interaction of cucurbitacins with human serum albumin: Thermodynamic
      characteristics and influence on the binding of site specific ligands.
AB  - Cucurbitacins (Cuc) are cytotoxic oxygenated triterpenes. Their binding to
      albumin may control their diffusion and consequently their biological effects.
      The specific binding site of Cuc to albumin is important to be defined as it
      could determine some of the drug interactions of the compounds. This paper deals
      with the interaction between human serum albumin and a series of four
      cucurbitacins (B, D, E and I) measured by fluorescence and circular dichroism
      spectroscopies. Cuc B and E at C25, are the acetylated forms of Cuc D and I. The
      binding parameters (K(a) and n) of Cuc B, D and E to albumin were determined at
      288, 293, 298 and 303K. Cuc B possesses the higher binding constant (K(a)) values
      followed by Cuc E and D. The thermodynamic parameters DeltaH, DeltaG and DeltaS
      were calculated. They indicated hydrophobic and electrostatic interactions for
      Cuc B, hydrophobic interaction for Cuc E, hydrophobic and hydrogen bond
      interactions for Cuc D. In addition to bilirubin, Cuc B, D, and E increased the
      binding constant values for warfarin to albumin, whereas they did not affect the
      binding of other ligands of site I such as chloroform and salicylate. The
      increase of the K(a) values of warfarin and bilirubin was associated with an
      increase of the binding constant value of cucurbitacin to albumin. Cuc I did not
      bind to albumin and could be considered less capable to affect the interaction of
      ligands to albumin than Cuc B, D and E. CD spectra indicated that Cuc binding to
      HSA was not associated with substantial structural changes of the protein.

PMID- 19380238
TI  - The flight and fight of Philippine nursing: soaring the fields of specialisation.

PMID- 19380239
TI  - Regulation of costimulation in the era of butyrophilins.
AB  - The butyrophilin and butyrophilin-like superfamily of molecules has garnered
      attention in the immunology world in the past few years as a result of the
      observation that the butyrophilin-like 2 molecule, BTNL2, can alter T cell
      responsiveness. Additional interest in this superfamily solidified following the
      discovery that genetic polymorphisms in BTNL2 are associated with predisposition
      to many human diseases. In this review, we will provide an overview of the
      members comprising the butyrophilin superfamily of molecules. We will then
      discuss BTNL2 immunomodulatory function, and BTNL2 structural associations with
      other costimulatory molecules. We will then draw your attention to some of the
      lesser-known butyrophilin superfamily members by describing the expression
      patterns of these molecules in human tissues and cells. And we will finish by
      hypothesizing on the potential influence on general immune homeostasis that might
      be mediated by this, thus-far little-studied, family of molecules.

PMID- 19380240
TI  - Tremor modulation in patients with Parkinson's disease compared to healthy
      counterparts during loaded postural holding.
AB  - Through examining tremor dynamics, the study sought to investigate the effects of
      load characteristics upon control strategies in patients with Parkinson's disease
      (PD) during postural holding. Eleven untreated patients and eleven healthy adults
      conducted a static pointing task with an outstretched arm, with a manipulated
      load of 100 g on the index finger. Oscillatory activities in the upper limb were
      contrasted between the unloaded and loaded conditions. The results showed that PD
      patients demonstrated abnormal modulation of tremor amplitude in the finger,
      hand, and upper arm in the opposing load condition. When the load was applied,
      the PD patients presented a nearly opposite pattern of tremor coupling between
      limb segments, contrary to the normal release and enhancement of tremor coupling
      in the finger-hand and hand-forearm complexes, respectively. Principal component
      analysis suggested that normal postural tremors could be explained by a load
      dependent component that had high communality with tremors of the distal
      segments. In contrast, major principal components of PD tremor were invariant to
      load addition. Multi-segment tremors in PD were atypically organized during
      loaded postural holding, signifying that coordinative control of the upper limb
      in the patients was impaired in the absence of exploitation of a germane distal
      strategy against inertial perturbation.

PMID- 19380241
TI  - Patterns of misinterpretation of adnexal masses on CT and MR in an academic
      radiology department.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to assess potential quality
      assurance (QA) issues in the diagnosis and characterization of adnexal masses on
      pelvic computed tomographic (CT) and magnetic resonance (MR) imaging studies.
      MATERIALS AND METHODS: Images from 128 women who had oophorectomies during a 16
      month period with CT and/or MR studies within 5 years of surgery (145 CT scans
      from 103 women and 49 MR studies from 42 women, with 17 having both MR and CT
      studies) were reviewed by three radiologists who assigned QA scores of 0 (no QA
      issue), 1 (minor issue with minimal impact on clinical care), or 2 (major issue
      with potential impact on clinical care). The difficulty of diagnosis was assigned
      a score of 0 (very difficult diagnosis to make), 1 (difficult but possible to
      make the diagnosis), or 2 (diagnosis should be made). The incidence of adnexal QA
      issues was calculated using total CT and MR pelvic examinations performed on
      women during the interval. RESULTS: Twenty-nine QA issues were identified in 28
      women in 17 of 145 CT studies (11.7%) and 12 of 49 MR examinations (24.5%) in
      women having adnexal surgery (17 of 11,194 [0.15%] of female pelvic CT studies
      and 12 of 603 [2.0%] of female pelvic MR studies performed in the time interval).
      Issues included missed lesions, lesions misidentified as leiomyomas, fat
      described in the lesion but not seen histologically, postmenopausal status of
      patient not considered, ultrasound correlation not recommended, and confusion of
      right and left sides. CONCLUSION: Errors in CT and MR studies regarding the
      diagnosis and characterization of adnexal masses in a highly enriched population
      of women undergoing adnexal surgery are common. Knowledge of the types of QA
      issues found in CT and MR studies of adnexal masses should aid in decreasing
      future errors.

PMID- 19380242
TI  - Impaired IL-10 transcription and release in animal models of Gaucher disease
      macrophages.
AB  - A number of studies have shown altered cytokine levels in serum from Gaucher
      disease patients, including changes in levels of the anti-inflammatory cytokine,
      interleukin-10 (IL-10). However, the source of IL-10, or the mechanisms leading
      to changes in IL-10 serum levels are not known. We now show that mouse
      macrophages treated with an active site-directed inhibitor of glucocerebrosidase,
      or macrophages from a mouse model of Gaucher disease, the L444P mouse, release
      significantly less IL-10 than their untreated counterparts, but that TNFalpha
      release is unaffected. These changes are due to reduced transcription of IL-10
      mRNA in macrophages. The reduction in IL-10 secretion observed in animal models
      of Gaucher disease macrophages may be of relevance to explain the increase in
      inflammation that is often observed in Gaucher disease.

PMID- 19380243
TI  - Dynamics and longevity of maternally-acquired antibodies to Taenia solium in
      piglets born to naturally infected sows.
AB  - This study was designed to investigate the longevity of maternally-acquired
      specific antibody (Ab) isotypes in piglets born to sows with Taenia solium
      cysticercosis. Four isotypes of anti-cysticercal immunoglobulins (IgG(total),
      IgG1, IgG2 and IgA), were assessed in sows naturally infected with T. solium
      (n=5) and their piglets (5/sow). Specific IgG2 and IgA responses were not
      detected in piglets at any sampling point. However, IgG(total) and IgG1 responses
      were detectable in sera from piglets from day 0 but not at 2months of age.
      Antibody profiles differed significantly over time between littermates and
      between piglets from different sows. These findings raise important questions as
      to the optimal timing of mass vaccination of piglets as a method of controlling
      cysticercosis in humans. The observed variations in the level of maternally
      acquired Abs amongst piglets will pose a major challenge to the implementation of
      vaccination programmes against T. solium cysticercosis.

PMID- 19380244
TI  - Theoretical studies on the interaction of modified pyrimidines and purines with
      purine riboswitch.
AB  - Recent experimental study [S.D. Gilbert, S.J. Mediatore, R.T. Batey, Modified
      pyrimidine specifically bind the purine riboswitch, J. Am. Chem. Soc. 128 (2006)
      14214-14215] demonstrated that the purine riboswitch could specifically bind some
      ligands other than purines such as amino-pyrimidines, and the authors proposed
      that the five-membered ring of purine was not required for recognition. To get
      insight into the interaction details, we used molecular docking method to
      investigate the interactions of a mutant form of guanine riboswitch with a series
      of amino-purines, amino-pyrimidines and imidazole derivatives, and employed
      molecular simulation method to study the dynamic behavior of the selected
      complexes. The calculation results reveal that (1) all the amino-purines and
      amino-pyrimidines bind in a same cavity composed of four nucleobases including
      U22, U47, U51 and U74, which is consistent with the experimental results, while
      the two imidazole derivatives adopt other binding modes; (2) the purines are
      engulfed within three-way junction motifs, but most pyrimidines only form two-way
      junctions with the riboswitch; (3) the number and position of amino substituents
      could seriously affect the binding of pyrimidines. As riboswitches are
      potentially excellent candidates for antibiotic therapeutics, these findings may
      be useful for understanding the range of compounds that riboswitch can
      specifically recognize.

PMID- 19380245
TI  - Synthesis of dendritic silver nanostructures by means of ultrasonic irradiation.
AB  - In this paper, a simple and effective route for the synthesis of silver dendritic
      nanostructures by means of ultrasonic irradiation has been developed. Well
      defined silver dendritic nanostructures were obtained by sonicating the aqueous
      solution of 0.04mol/L silver nitrate with 4.0mol/L isopropanol as reducing agent
      and 0.01mol/L PEG400 as disperser for 2h. The effects of the irradiation time,
      the concentration of Ag(+) and the molar ratio of PEG to AgNO(3) on the
      morphology of silver nanostructures were discussed. The structures of the
      obtained samples were characterized by transmission electron microscopy (TEM),
      selected area electron diffraction (SAED) and X-ray powder diffraction (XRD), and
      the chemical composition of the dendrites was examined by energy-dispersive X-ray
      spectrum (EDS).

PMID- 19380246
TI  - Positive patient outcome after spinal manipulation in a case of cervical angina.

PMID- 19380247
TI  - Determination of berberine and the study of fluorescence quenching mechanism
      between berberine and enzyme-catalyzed product.
AB  - A new method for determining berberine has been established based on the
      principle of fluorescence quenching. The calibration curve was found to be linear
      between F(0)/F and the concentration of berberine with the range of 3.00-20.0
      microg mL(-1). The detection limit was 0.51 microg mL(-1) and the relative
      standard derivative was 0.18%. Effects of pH, foreign ions and the optimization
      of variables on the determination of berberine have been examined. The mechanism
      of the fluorescence quenching has been discussed. The binding constant and the
      number of binding sites were 1.70x10(6) L mol(-1) and 1.14, respectively. The
      data, DeltaH = 42.71 kJ mol(-1), DeltaS = 264.3 J K(-1) mol(-1) and the mean
      value DeltaG = -39.65 kJ mol(-1) were estimated which showed that the reaction
      was spontaneous and endothermic. The main binding force was hydrophobic force
      because both DeltaH and DeltaS were positive.

PMID- 19380248
TI  - 1H NMR titration and quantum calculation for the inclusion complexes of cis
      cyclooctene, cis, cis-1, 3-cyclooctadiene and cis, cis-1, 5-cyclooctadiene with
      beta-cyclodextrin.
AB  - The inclusion behavior of cis-cyclooctene, cis, cis-1, 3-cyclooctadiene and cis,
      cis-1, 5-cyclooctadiene with beta-cyclodextrin (beta-CD) was studied by using
      (1)H NMR method in D(2)O/CD(3)OD solution and PM3 quantum-chemical simulation in
      vacuum. The experimental results indicate that each guest molecule penetrates
      deeply into beta-CD cavity and forms equimolecular inclusion complex with the
      host. The association constants of the complexes were determined by non-linear
      least-square method on the bases of the conversion-dependent chemical shift of
      two protons of the host molecule. The inclusion process and the most probable
      structure of the inclusion complexes were simulated using PM3 energy scanning and
      optimization. The trend of stability of the three inclusion complexes deduced
      from their calculated stabilization energies agrees well with the order of their
      association constants obtained from NMR experiments.

PMID- 19380249
TI  - Effect of solvent hydrogen bonding on the photophysical properties of
      intramolecular charge transfer probe trans-ethyl p-(dimethylamino) cinamate and
      its derivative.
AB  - Intramolecular charge transfer (ICT) behavior of trans-ethyl p-(dimethylamino)
      cinamate (EDAC) and 4-(dimethylamino) cinnamic acid (DMACA) were studied by
      steady state absorption and emission, picosecond time-resolved fluorescence
      experiments in various pure and mixed solvent systems. The large fluorescence
      spectral shift in more polar solvents indicates an efficient charge transfer from
      the donor site to the acceptor moiety in the excited state compared to the ground
      state. The energy for 0,0 transition (nu(0,0)) for EDAC shows very good linear
      correlation with static solvent dielectric property; however, fluorescence
      emission maximum, stokes shift and fluorescence quantum yield show significant
      deviation from linearity in polar protic solvents, indicating a large
      contribution of solvent hydrogen bonding on the excited state relaxation
      mechanism. A quantitative estimation of contribution from different
      solvatochromic parameters was made using linear free energy relationship based on
      Kamlet-Taft equation.

PMID- 19380250
TI  - Studies on best dose of X-ray for Hep-2 cells by using FTIR, UV-vis absorption
      spectroscopy and flow cytometry.
AB  - We report here the use of Fourier transform infrared spectroscopy (FTIR),
      ultraviolet-visible (UV-vis) absorption spectroscopy, and flow cytometry (FCM) to
      analysis the best dose of X-ray for human laryngeal squamous cell carcinoma cell
      lines (Hep-2). Our analysis indicates specific FTIR and UV-vis spectral
      differences between X-irradiated and normal Hep-2 cells. In addition, striking
      spectral differences are seen in FTIR spectra in the ratios at 2925/2958 and
      1654/1542 cm(-1). These two ratios of the X-irradiated cells for 8 Gy dose group
      with value of 1.07+/-0.025 and 1.184+/-0.013, respectively, were more notable
      (mean+/-S.D., n=5, P<0.05) compared with that of the cells for the controls. UV
      vis absorption spectra analysis shows X-ray irradiation disturbed the metabolism
      of phenylalanine and tyrosine intracellular, maybe, which was caused by cell
      cycle arrest. Spectroscopy analysis suggests 8 Gy is a better dose of X-ray for
      lowering the canceration degree of Hep-2 cells. Moreover, FCM analysis shows the
      apoptosis of X-irradiated cells depended on the radiation dose to some extent,
      but it was not linear. The total apoptosis ratio with value of (20.793+/-1.133)%
      (P<0.01, n=5) for the 12 Gy dose group was the maximum, however, the maximum
      apoptosis ratio per Gray (total apoptosis ratio/radiation dose) was the cells of
      the 2 Gy dose group with value of (4.887+/-0.211)% (P<0.05, n=5). Our data
      suggest that Hep-2 cells are given 2 Gy radiation of X-ray once a time, 8 Gy per
      week (accumulatively), the effect for lowering the canceration degree and
      restraining the proliferation of Hep-2 cells will be better.

PMID- 19380251
TI  - Attentional cortical responses to enlarged faces are related to body fat in
      normal weight subjects: an electroencephalographic study.
AB  - OBJECTIVE: Here we tested the hypothesis that in normal weight subjects,
      attentional cortical responses to the enlargement of faces are related to
      features of body weight, as a basis for future studies on the role of
      neurocognitive mechanisms in eating and weight disorders. METHODS:
      Electroencephalographic data were recorded in 15 normal weight adults during a
      visual "oddball" paradigm. The subjects were given frequent (70%) and rare (30%)
      stimuli depicting faces (FACE), food (FOOD), and landscapes (CONTROL). The task
      was to click the mouse after the rare stimuli. These stimuli depicted the same
      frequent stimuli graphically dilated by 25% along the horizontal axis. Analysis
      of bioelectrical impedance indexed subjects' body fat percentage. Cortical
      attentional responses were probed by the difference between positive event
      related potentials peaking around 200-600 ms post-stimulus for the frequent minus
      rare stimuli (P300). LORETA estimated P300 cortical sources. RESULTS: Main
      results showed that in the FACE condition, there was a negative correlation
      between the body fat percentage and the reaction time to the rare stimuli, and a
      positive correlation between the body fat percentage and the amplitude of
      prefrontal P300 sources (p<0.05). CONCLUSIONS: These results disclose a
      relationship between body fat and prefrontal attentional processes to body image
      in normal weight adults. SIGNIFICANCE: The present study motivates future
      research testing the hypothesis that this relationship might be altered in
      patients with eating and weight disorders.

PMID- 19380253
TI  - Regulation of the aging process by autophagy.
AB  - Autophagy is involved in cellular protein and organelle degradation, which is
      mediated by the lysosomal pathway. Autophagocytosis has a key role in cellular
      housekeeping by removing damaged organelles. During aging, the efficiency of
      autophagic degradation declines and intracellular waste products accumulate. In
      Caenorhabditis elegans, there is clear evidence that lifespan is linked to the
      capacity to regulate autophagy. Recent studies have revealed that the same
      signaling factors regulate both aging and autophagocytosis, thus highlighting the
      role of autophagy in the regulation of aging and age-related degenerative
      diseases. Here, we examine in detail the interactions of the signaling network
      involving longevity factors SIRT1, mTOR, FoxO3, NF-kappaB and p53 in the
      regulation of autophagy. We discuss the possibility that these well-known stress
      resistance and longevity factors regulate the aging process via autophagy.

PMID- 19380252
TI  - The PI3K-PTEN tug-of-war, oxidative stress and retinal degeneration.
AB  - The retinal pigment epithelium (RPE) is indispensable for photoreceptor function,
      not only because it provides functional photopigments to photoreceptors, but also
      because it eliminates oxidatively damaged materials from photoreceptors.
      Maintaining homeostatic antioxidative programs that support a healthy RPE is
      therefore important for the normal functioning of the eye. These homeostatic
      mechanisms, however, often fail in aged RPE cells that have been exposed
      repeatedly to excessive oxidative stress. When RPE cells succumb to oxidative
      stress, their death contributes to the development of retinal degenerative
      diseases such as age-related macular degeneration. Recent studies have
      highlighted the importance of reciprocal phosphoinositide signaling events
      orchestrated by phosphoinositide 3-kinase (PI3K) and phosphatase and tensin
      homolog (PTEN) in the homeostatic programs that protect RPE cells against
      oxidative stress. Here, we discuss the role of PI3K signaling pathways in RPE
      cells and suggest that they might be crucial targets of oxidative molecules that
      initiate early pathological events in retinal degenerative diseases.

PMID- 19380254
TI  - Plasma levels of FL and SDF-1 and expression of FLT-3 and CXCR4 on CD34+ cells
      assessed pre and post hematopoietic stem cell mobilization in patients with
      hematologic malignancies and in healthy donors.
AB  - Peripheral blood stem cells (PBSC) became the main source of cells for autologous
      transplantation. Alterations in the expression of adhesion molecules are
      essential in the CD34+ cells mobilization process. These molecules are involved
      in the interaction between hematopoietic and stromal cells and they have been
      disclosed as a considerable factor to the trafficking and homing of the CD34+
      progenitor cells. This is a non-randomized PBSC mobilization study designed to
      evaluate the influence and behavior of FL and SDF-1 and their receptors in two
      different moments, prior and after HPCs mobilization, with the yield of CD34+
      cells collected by apheresis. There was higher concentration of FL and lower of
      SDF-1 plasma level at post than pre PBSC mobilization (p=0.001 and p=0.012,
      respectively) regarding all individuals searched, but without any correlation
      with a good yield of CD34+ cells. However, CXCR4 expressions on the CD34+ cells
      from bone marrow aspirates (BMA), at pre and post mobilization showed a
      difference statistical significant for those individuals with good yield of CD34+
      cells (p=0,036), but not achieved for poor yield (p=0,156). There was a higher
      expression of CXCR4 in steady-state for the successfully individuals than for
      those unsuccessfully (529.84+/-54.68 and 496.31+/-97.51, respectively). In
      conclusion, we confirmed the important role of CXCR4/SDF-1 axis in the process of
      PBSC mobilization.

PMID- 19380256
TI  - Experimental and clinical applications of quantitative sensory testing applied to
      skin, muscles and viscera.
AB  - Quantification of the human painful sensory experience is an essential step in
      the translation of knowledge from animal nociception to human pain. Translational
      models for assessment of pain are very important, as such models can be used in:
      1) basic mechanistic studies in healthy volunteers; 2) clinical studies for
      diagnostic and monitoring purposes; 3) pharmacological studies to evaluate
      analgesic efficacy of new and existing compounds. Quantitative pain assessment,
      or quantitative sensory testing (QST), provides psychophysical methods that
      systematically document alterations and reorganization in nervous system function
      and, in particular, the nociceptive system. QST is defined as the determination
      of thresholds or stimulus response curves for sensory processing under normal and
      pathophysiological conditions. The modern concept of advanced QST for
      experimental pain assessment is a multimodality, multitissue approach where
      different pain modalities (thermal, mechanical, electrical, and chemical) are
      applied to different tissues (skin, muscles, and viscera) and the responses are
      assessed by psychophysical methods (thresholds and stimulus-response functions).
      Many new and advanced technologies have been developed to help relieve evoked,
      standardized, and painful reactions. Assessing pain has become a question of
      solving a multi-input, multi-output problem, with the solution providing the
      possibility of teasing out which pain pathways and mechanisms are involved,
      impaired, or affected. PERSPECTIVE: Many methodologies have been developed for
      quantitative assessment of pain perception and involved mechanisms. This paper
      describes the background for the different methods, the use in basic pain
      experiments on healthy volunteers, how they can be applied in drug profiling, and
      the applications in clinical practice.

PMID- 19380255
TI  - Leptin replacement restores supraspinal cholinergic antinociception in leptin
      deficient obese mice.
AB  - A single gene deletion causes lack of leptin and obesity in B6.V-Lep(ob) (obese;
      ob) mice compared with wild-type C57BL/6J (B6) mice. This study compared the
      phenotype of nociception and supraspinal antinociception in obese and B6 mice by
      testing 2 hypotheses: (1) microinjection of cholinomimetics or an adenosine
      receptor agonist, but not morphine, into the pontine reticular formation (PRF) is
      antinociceptive in B6 but not obese mice, and (2) leptin replacement in obese
      mice attenuates differences in nociceptive responses between obese and B6 mice.
      Adult male mice (n = 22) were implanted with microinjection guide tubes aimed for
      the PRF. The PRF was injected with neostigmine, carbachol, nicotine, N(6)-p
      sulfophenyladenosine (SPA), morphine, or saline (control), and latency to paw
      withdrawal (PWL) from a thermal stimulus was recorded. B6 and ob mice did not
      differ in PWL after saline microinjection into the PRF. Neostigmine, carbachol,
      and SPA caused PWL to increase significantly in B6 but not obese mice. An
      additional 15 obese mice were implanted with osmotic pumps that delivered leptin
      for 7 days. Leptin replacement in obese mice restored the analgesic effect of PRF
      neostigmine to the level displayed by B6 mice. The results show for the first
      time that leptin significantly alters supraspinal cholinergic antinociception.
      PERSPECTIVE: This study specifies a brain region (the pontine reticular
      formation), cholinergic neurotransmission, and a protein (leptin) modulating
      thermal nociception. The results are relevant for efforts to understand the
      association between obesity, disordered sleep, and hyperalgesia.

PMID- 19380257
TI  - Testing traditional cupping therapy.

PMID- 19380258
TI  - Effects of intramuscular anesthesia on the expression of primary and referred
      pain induced by intramuscular injection of hypertonic saline.
AB  - Intramuscular injection of hypertonic saline produces pain in the belly of the
      injected muscle (primary pain) and, often, pain that projects distally (referred
      pain). While it is known that referred pain can be induced during complete
      sensory block of the distal site, there is little evidence as to whether the
      perception of referred pain depends on ongoing input from the primary stimulus.
      We assessed whether blocking the noxious input following the induction of pain
      blocks the primary but not the referred pain. A cannula was inserted into the
      tibialis anterior muscle in 15 subjects (8 male, 7 female). In a quasi-random
      crossover design conducted over 2 experimental sessions, each subject received a
      bolus intramuscular injection of .5 mL of 5% hypertonic saline, followed 90
      seconds later by either: A) A second bolus injection or; B) An injection of 2 mL
      lignocaine through the same cannula. Protocol A was followed 60 seconds later by
      either a sham injection or an injection of lignocaine, while protocol B was
      followed 60 seconds later by either a sham injection or an injection of
      hypertonic saline. Subjects mapped the areas of primary and referred pain, and
      rated the intensities at these sites every 30 seconds until the cessation of
      pain. In all subjects, the area and intensity of primary pain rapidly disappeared
      within 7.5 minutes of intramuscular lignocaine injection (P < .02 relative to the
      nonanesthesia condition). With the exception of 2 subjects, in whom the referred
      pain continued in the absence of primary pain, the referred pain declined in
      parallel with local pain: the mean total pain intensity declined by 74% in both
      regions. We conclude that the maintenance of referred muscle pain usually depends
      on ongoing noxious inputs from the site of primary muscle pain. PERSPECTIVE:
      Referred pain is a significant clinical problem, and commonly occurs with pain
      originating in muscle but not from skin. It is important to know the primary
      source of the pain so that treatment can be directed to this site rather to the
      site of referral.

PMID- 19380259
TI  - Effects of traditional cupping therapy in patients with carpal tunnel syndrome: a
      randomized controlled trial.
AB  - We investigated the effectiveness of cupping, a traditional method of treating
      musculoskeletal pain, in patients with carpal tunnel syndrome (CTS) in an open
      randomized trial. n = 52 outpatients (58.5 +/- 8.0 years) with neurologically
      confirmed CTS were randomly assigned to either a verum (n = 26) or a control
      group (n = 26). Verum patients were treated with a single application of wet
      cupping, and control patients with a single local application of heat within the
      region overlying the trapezius muscle. Patients were followed up on day 7 after
      treatment. The primary outcome, severity of CTS symptoms (VAS), was reduced from
      61.5 +/- 20.5 to 24.6 +/- 22.7 mm at day 7 in the cupping group and from 67.1 +/-
      20.2 to 51.7 +/- 23.9 mm in the control group [group difference -24.5mm (95%CI 
      36.1; -2.9, P < .001)]. Significant treatment effects were also found for the
      Levine CTS-score (-.6 pts: 95%CI -.9; -.2, P = .002), neck pain (-12.6mm; 95%CI 
      18.8; -6.4, P < .001), functional disability (DASH-Score) (-11.1 pts; 95%CI 
      17.1; -5.1, P < .001), and physical quality of life (.3; 95%CI .0; .3, P = .048).
      The treatment was safe and well tolerated. We conclude that cupping therapy may
      be effective in relieving the pain and other symptoms related to CTS. The
      efficacy of cupping in the long-term management of CTS and related mechanisms
      remains to be clarified. PERSPECTIVE: The results of a randomized trial on the
      clinical effects of traditional cupping therapy in patients with carpal tunnel
      syndrome are presented. Cupping of segmentally related shoulder zones appears to
      alleviate the symptoms of carpal tunnel syndrome.

PMID- 19380260
TI  - [Bilateral cholesteatoma: a rare cause of hearing loss and chronic otorrhea].

PMID- 19380261
TI  - [Tuberculosis during pregnancy and congenital tuberculosis].

PMID- 19380262
TI  - Preparation and characterization of a novel strontium-containing calcium
      phosphate cement with the two-step hydration process.
AB  - A novel Sr-containing calcium phosphate cement (CPC) with excellent compressive
      strength, good radiopacity and suitable setting time was developed in this work.
      The two-step hydration reaction resulted in a high compressive strength, with a
      maximum of up to 74.9MPa. Sr was doped into the calcium-deficient hydroxyapatite
      as a hydrated product during the hydration reaction of the CPC. Because of the
      existence of Sr element and the compact microstructure after hydration, the Sr
      containing CPC shows good radiopacity. It is expected to be used in orthopedic
      and maxillofacial surgery for bone defects repairing.

PMID- 19380263
TI  - Free posterior interosseous artery perforator flap for finger reconstruction.
AB  - We successfully transplanted two free posterior interosseous artery perforator
      flaps that had been harvested simultaneously from a single posterior interosseous
      artery system to the index and middle fingers of a 19-year-old man. Our case
      suggests that multiple free perforator flaps can be prepared from a single
      posterior interosseous artery system.

PMID- 19380264
TI  - Efficacy of 'rugby-ball shape' skin grafting using external wire frame fixation
      without tarsorrhaphy for lower eyelid reconstruction.

PMID- 19380265
TI  - Muscle stimulation waveform timing patterns for upper and lower leg muscle groups
      to increase muscular endurance in functional electrical stimulation pedaling
      using a forward dynamic model.
AB  - Functional electrical stimulation (FES) of pedaling provides a means by which
      individuals with spinal cord injury can obtain cardiorespiratory exercise.
      However, the early onset of muscle fatigue is a limiting factor in the
      cardiorespiratory exercise obtained while pedaling an FES ergometer. One
      objective of this study was to determine muscle excitation timing patterns to
      increase muscle endurance in FES pedaling for three upper leg muscle groups and
      to compare these timing patterns to those used in a commercially available FES
      ergometer. The second objective was to determine excitation timing patterns for a
      lower leg muscle group in conjunction with the three upper leg muscle groups. The
      final objective was to determine the mechanical energy contributions of each of
      the muscle groups to drive the crank. To fulfill these objectives, we developed a
      forward dynamic simulation of FES pedaling to determine electrical stimulation on
      and off times that minimize the muscle stress-time integral of the stimulated
      muscles. The computed electrical stimulation on and off times differed from those
      utilized by a commercially available FES ergometer and resulted in 17% and 11%
      decrease in the muscle stress-time integral for the three upper leg muscle groups
      and four upper and lower leg muscle groups, respectively. Also, the duration of
      muscle activation by the hamstrings increased by 5% over a crank cycle for the
      computed stimulation on and off times, and the mechanical energy generated by the
      hamstrings increased by 20%. The lower leg muscle group did not generate
      sufficient mechanical energy to reduce the energy contributions of the upper leg
      muscle groups. The computed stimulation on and off times could prolong FES
      pedaling, and thereby provide improved cardiorespiratory and muscle training
      outcomes for individuals with spinal cord injury. Including the lower leg muscle
      group in FES pedaling could increase cardiorespiratory demand while not affecting
      the endurance of the muscles involved in the pedaling task.

PMID- 19380266
TI  - Nonlinear mixed effects to improve glucose minimal model parameter estimation: a
      simulation study in intensive and sparse sampling.
AB  - Intravenous glucose tolerance test (IVGTT) minimal model parameters are commonly
      estimated by weighted least squares (WLSs) on each subject data. Sometimes, with
      sparse data, individual parameters cannot be satisfactorily obtained. In such
      cases, a population approach could be preferable. These methods allow borrowing
      information across all subjects simultaneously, quantifying population features
      directly, and subsequently, deriving individual parameter estimates. In this
      paper, we assessed different estimation methods on simulated datasets. Besides
      the standard WLS approach, we applied iterative procedures (iterative two-stage
      (ITS) and global two-stage (GTS) methods) as well as nonlinear mixed-effects
      models (NLMEMs), where the likelihood is based on model linearization: first
      order (FO), FO conditional estimation (FOCE), and Laplace (LAP) approximations.
      The synthetic dataset, initially very rich, was progressively reduced (by 50% and
      75%) in order to assess the robustness of the results in sparsely sampled
      situations. Our results show that, even with intensive sampling, population
      approaches provide more reliable parameter estimates. Moreover, these estimates
      are remarkably more robust when the data become scarce. ITS and GTS encounter
      critical problems when single subjects have very poor sampling schedules, whereas
      the NLMEM (excluding FO) methods are more versatile and able to cope with such
      situations. FOCE appears as the most satisfactory approach.

PMID- 19380267
TI  - Comments on "phase-shifting for nonseparable 2-D Haar wavelets".
AB  - In their recent paper, Alnasser and Foroosh derive a wavelet-domain (in-band)
      method for phase-shifting of 2-D "nonseparable" Haar transform coefficients.
      Their approach is parametrical to the (a priori known) image translation. In this
      correspondence, we show that the utilized transform is in fact the separable Haar
      discrete wavelet transform (DWT). As such, wavelet-domain phase shifting can be
      performed using previously-proposed phase-shifting approaches that utilize the
      overcomplete DWT (ODWT), if the given image translation is mapped to the phase
      component and in-band position within the ODWT.

PMID- 19380268
TI  - Active mask segmentation of fluorescence microscope images.
AB  - We propose a new active mask algorithm for the segmentation of fluorescence
      microscope images of punctate patterns. It combines the (a) flexibility offered
      by active-contour methods, (b) speed offered by multiresolution methods, (c)
      smoothing offered by multiscale methods, and (d) statistical modeling offered by
      region-growing methods into a fast and accurate segmentation tool. The framework
      moves from the idea of the "contour" to that of "inside and outside," or masks,
      allowing for easy multidimensional segmentation. It adapts to the topology of the
      image through the use of multiple masks. The algorithm is almost invariant under
      initialization, allowing for random initialization, and uses a few easily tunable
      parameters. Experiments show that the active mask algorithm matches the ground
      truth well and outperforms the algorithm widely used in fluorescence microscopy,
      seeded watershed, both qualitatively, as well as quantitatively.

PMID- 19380269
TI  - Video event classification and image segmentation based on noncausal
      multidimensional hidden Markov models.
AB  - In this paper, we propose a novel solution to an arbitrary noncausal,
      multidimensional hidden Markov model (HMM) for image and video classification.
      First, we show that the noncausal model can be solved by splitting it into
      multiple causal HMMs and simultaneously solving each causal HMM using a fully
      synchronous distributed computing framework, therefore referred to as distributed
      HMMs. Next we present an approximate solution to the multiple causal HMMs that is
      based on an alternating updating scheme and assumes a realistic sequential
      computing framework. The parameters of the distributed causal HMMs are estimated
      by extending the classical 1-D training and classification algorithms to multiple
      dimensions. The proposed extension to arbitrary causal, multidimensional HMMs
      allows state transitions that are dependent on all causal neighbors. We, thus,
      extend three fundamental algorithms to multidimensional causal systems, i.e., 1)
      expectation-maximization (EM), 2) general forward-backward (GFB), and 3) Viterbi
      algorithms. In the simulations, we choose to limit ourselves to a noncausal 2-D
      model whose noncausality is along a single dimension, in order to significantly
      reduce the computational complexity. Simulation results demonstrate the superior
      performance, higher accuracy rate, and applicability of the proposed noncausal
      HMM framework to image and video classification.

PMID- 19380270
TI  - On color texture normalization for active appearance models.
AB  - The extension of the standard grayscale active appearance model (AAM) techniques
      to color images is investigated. Prior work in this field has mainly focused on
      RGB color models which did not demonstrate noticeable benefits over grayscale
      models from the point of view of convergence accuracy. We improve on previous
      work by normalizing the color texture vector separately for intensity and
      chromaticity components. Where an appropriate color space is chosen, we
      demonstrate improvements in convergence accuracy as well as image synthesization
      quality for AAMs. Optimal results are achieved when a color space in which the
      image channels are strongly decorrelated is chosen. Our best results are achieved
      using the I1I2I3 color space, originally proposed by Ohta.

PMID- 19380271
TI  - Sparse image reconstruction for molecular imaging.
AB  - The application that motivates this paper is molecular imaging at the atomic
      level. When discretized at subatomic distances, the volume is inherently sparse.
      Noiseless measurements from an imaging technology can be modeled by convolution
      of the image with the system point spread function (psf). Such is the case with
      magnetic resonance force microscopy (MRFM), an emerging technology where imaging
      of an individual tobacco mosaic virus was recently demonstrated with nanometer
      resolution. We also consider additive white Gaussian noise (AWGN) in the
      measurements. Many prior works of sparse estimators have focused on the case when
      H has low coherence; however, the system matrix H in our application is the
      convolution matrix for the system psf. A typical convolution matrix has high
      coherence. This paper, therefore, does not assume a low coherence H. A discrete
      continuous form of the Laplacian and atom at zero (LAZE) p.d.f. used by Johnstone
      and Silverman is formulated, and two sparse estimators derived by maximizing the
      joint p.d.f. of the observation and image conditioned on the hyperparameters. A
      thresholding rule that generalizes the hard and soft thresholding rule appears in
      the course of the derivation. This so-called hybrid thresholding rule, when used
      in the iterative thresholding framework, gives rise to the hybrid estimator, a
      generalization of the lasso. Estimates of the hyperparameters for the lasso and
      hybrid estimator are obtained via Stein's unbiased risk estimate (SURE). A
      numerical study with a Gaussian psf and two sparse images shows that the hybrid
      estimator outperforms the lasso.

PMID- 19380272
TI  - Opti-acoustic stereo imaging: on system calibration and 3-D target
      reconstruction.
AB  - Utilization of an acoustic camera for range measurements is a key advantage for 3
      D shape recovery of underwater targets by opti-acoustic stereo imaging, where the
      associated epipolar geometry of optical and acoustic image correspondences can be
      described in terms of conic sections. In this paper, we propose methods for
      system calibration and 3-D scene reconstruction by maximum likelihood estimation
      from noisy image measurements. The recursive 3-D reconstruction method utilized
      as initial condition a closed-form solution that integrates the advantages of two
      other closed-form solutions, referred to as the range and azimuth solutions.
      Synthetic data tests are given to provide insight into the merits of the new
      target imaging and 3-D reconstruction paradigm, while experiments with real data
      confirm the findings based on computer simulations, and demonstrate the merits of
      this novel 3-D reconstruction paradigm.

PMID- 19380273
TI  - A multifaceted perspective at data analysis: a study in collaborative intelligent
      agents.
AB  - Multiagent systems are inherently associated with their distributivity, which
      enforces a great deal of communication mechanisms. To effectively arrive at
      meaningful solutions in a vast array of problem-solving tasks, it becomes
      imperative to establish a sound machinery of reconciling findings which might
      form partial solutions to an overall problem. In this paper, we focus on a broad
      category of problems of collaborative data analysis realized by a collection of
      agents having access to their individual data and exchanging findings through
      their collaboration activities. Such problems of data analysis arise in the
      context of building a global view at a certain phenomenon (process) by viewing it
      from different perspectives (and thus engaging various collections of attributes
      by various agents). Our goal is to develop some interaction between the agents so
      that they could form an overall perspective, where the knowledge available
      locally is shared and reconciled. The underlying format of knowledge built by the
      agents is that of information granules and fuzzy sets in particular. We develop a
      comprehensive optimization scheme and discuss its two-phase nature in which the
      communication phase of the granular findings intertwines with the local
      optimization being realized by the agents at the level of the individual datasite
      and exploits the evidence collected from other sites. We show how the mechanism
      of fuzzy granulation realized in the form of a well-known fuzzy c-means (FCM)
      clustering can be augmented to support collaborative activities required by the
      agents. For this purpose, we introduce augmented versions of the original
      objective function used in the FCM and derive algorithmic details. We also
      discuss an issue of optimizing the strength of collaborative linkages, so that
      the reconciled findings attain the highest level of consistency (agreement). The
      presented experimental studies include some synthetic data and selected data sets
      coming from the Machine Learning repository.

PMID- 19380274
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- 19380275
TI  - Software engineering and scale-free networks.
AB  - Complex-network theory is a new approach in studying different types of large
      systems in both the physical and the abstract worlds. In this paper, we have
      studied two kinds of network from software engineering: the component dependence
      network and the sorting comparison network (SCN). It is found that they both show
      the same scale-free property under certain conditions as complex networks in
      other fields. These results suggest that complex-network theory can be a useful
      approach to the study of software systems. The special properties of SCNs provide
      a more repeatable and deterministic way to study the evolution and optimization
      of complex networks. They also suggest that the closer a sorting algorithm is to
      the theoretical optimal limit, the more its SCN is like a scale-free network.
      This may also indicate that, to store and retrieve information efficiently, a
      concept network might need to be scale-free.

PMID- 19380276
TI  - A pheromone-rate-based analysis on the convergence time of ACO algorithm.
AB  - Ant colony optimization (ACO) has widely been applied to solve combinatorial
      optimization problems in recent years. There are few studies, however, on its
      convergence time, which reflects how many iteration times ACO algorithms spend in
      converging to the optimal solution. Based on the absorbing Markov chain model, we
      analyze the ACO convergence time in this paper. First, we present a general
      result for the estimation of convergence time to reveal the relationship between
      convergence time and pheromone rate. This general result is then extended to a
      two-step analysis of the convergence time, which includes the following: 1) the
      iteration time that the pheromone rate spends on reaching the objective value and
      2) the convergence time that is calculated with the objective pheromone rate in
      expectation. Furthermore, four brief ACO algorithms are investigated by using the
      proposed theoretical results as case studies. Finally, the conclusions of the
      case studies that the pheromone rate and its deviation determine the expected
      convergence time are numerically verified with the experiment results of four one
      ant ACO algorithms and four ten-ant ACO algorithms.

PMID- 19380277
TI  - A new phase-correlation-based iris matching for degraded images.
AB  - In this paper, we present a new phase-correlation-based iris matching approach in
      order to deal with degradations in iris images due to unconstrained acquisition
      procedures. Our matching system is a fusion of global and local Gabor phase
      correlation schemes. The main originality of our local approach is that we do not
      only consider the correlation peak amplitudes but also their locations in
      different regions of the images. Results on several degraded databases, namely,
      the CASIA-BIOSECURE and Iris Challenge Evaluation 2005 databases, show the
      improvement of our method compared to two available reference systems, Masek and
      Open Source for Iris (OSRIS), in verification mode.

PMID- 19380278
TI  - Current concepts in stereotactic radiosurgery - a neurosurgical and
      radiooncological point of view.
AB  - Stereotactic radiosurgery is related to the history of "radiotherapy" and
      "stereotactic neurosurgery". The concepts for neurosurgeons and radiooncologists
      have been changed during the last decade and have also transformed neurosurgery.
      The gamma knife and the stereotactically modified linear accelerator (LINAC) are
      radiosurgical equipments to treat predetermined intracranial targets through the
      intact skull without damaging the surrounding normal brain tissue. These
      technical developments allow a more precise intracranial lesion control and offer
      even more conformal dose plans for irregularly shaped lesions. Histological
      determination by stereotactic biopsy remains the basis for any otherwise
      undefined intracranial lesion. As a minimal approach, it allows functional
      preservation, low risk and high sensitivity. Long-term results have been
      published for various indications. The impact of radiosurgery is presented for
      the management of gliomas, metastases, brain stem lesions, benign tumours and
      vascular malformations and selected functional disorders such as trigeminal
      neuralgia. In AVM's it can be performed as part of a multimodality strategy
      including resection or endovascular embolisation. Finally, the technological
      advances in radiation oncology as well as stereotactic neurosurgery have led to
      significant improvements in radiosurgical treatment opportunities. Novel
      indications are currently under investigation. The combination of both, the
      neurosurgical and the radiooncological expertise, will help to minimize the risk
      for the patient while achieving a greater treatment success.

PMID- 19380279
TI  - Neurofibromatosis.
AB  - Neurofibromatosis (NF) is one of the most common genetic disorders. Inherited in
      an autosomal dominant fashion, this phacomatosis is classified into two
      genetically distinct subtypes characterized by multiple cutaneous lesions and
      tumors of the peripheral and central nervous system. Neurofibromatosis type 1
      (NF1), also referred to as Recklinghausen's disease, affects about 1 in 3500
      individuals and presents with a variety of characteristic abnormalities of the
      skin and the peripheral nervous system. Neurofibromatosis type 2 (NF2),
      previously termed central neurofibromatosis, is much more rare occurring in less
      than 1 in 25 000 individuals. Often first clinical signs of NF2 become apparent
      in the late teens with a sudden loss of hearing due to the development of bi- or
      unilateral vestibular schwannomas. In addition NF2 patients may suffer from
      further nervous tissue tumors such as meningiomas or gliomas. This review
      summarizes the characteristic features of the two forms of NF and outlines
      commonalities and distinctions between NF1 and NF2.

PMID- 19380280
TI  - The effects of physical exercise on plasma levels of relaxin, NTproANP, and
      NTproBNP in patients with ischemic heart disease.
AB  - The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as
      a pregnancy hormone, has gained interest as a potential humoral mediator in human
      heart failure. Controversy exists about the relation between plasma levels of RLX
      and the severity of heart failure. The present study was designed to determine
      the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT
      proBNP) during physical exercise in patients with ischemic heart disease (IHD)
      and to relate hormone levels to peak cardiac power output (CPO) as a measure of
      cardiopulmonary function with prognostic relevance. 40 patients with IHD were
      studied during right-heart-catheterization at rest and during supine bicycle
      ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise,
      and after recovery. NT-proANP and NT-proBNP levels increased during maximal
      charge, and recovery while RLX levels decreased. Cardiac power output at maximal
      charge correlated inversely with NTproANP and NTproBNP but positively with RLX.
      Patients with high degree heart failure (CPO<1.96 W) had higher NTproANP and
      NTproBNP and lower RLX levels than patients with low degree heart failure. While
      confirming the role of NTproANP and NTproBNP as markers for the severity of heart
      failure, the present data do not support the concept that plasma levels of RLX
      are related to the severity of myocardial dysfunction and that systemic RLX acts
      as a compensatory vasodilatatory response hormone in ischemic heart disease.

PMID- 19380281
TI  - Differential number of CD34+, CD133+ and CD34+/CD133+ cells in peripheral blood
      of patients with congestive heart failure.
AB  - BACKGROUND: Endothelial progenitor cells (EPC) which are characterised by the
      simulateous expression of CD34, CD133 and vascular endothelial growth receptor 2
      (VEGF 2) are involved in the pathophysiology of congestive heart failure (CHF)
      and their number and function is reduced in CHF. But so far our knowledge about
      the number of circulating hematopoietic stem/ progenitor cells (CPC) expressing
      the early hematopoietic marker CD133 and CD34 in CHF is spares and therefore we
      determined their number and correlated them with New York Heart Association
      (NYHA) functional class. METHODS: CD34 and CD133 surface expression was
      quantified by flow cytometry in the peripheral venous blood of 41 healthy adults
      and 101 patients with various degrees of CHF. RESULTS: CD34+, CD133+ and
      CD34+/CD133+ cells correlated inversely with age. Both the number of CD34+ and of
      CD34+/CD133+ cells inversely correlated with NYHA functional class. The number of
      CD133+ cells was not affected by NYHA class. Furthermore the number of CD133+
      cells did not differ between control and CHF patients. CONCLUSION: In CHF the
      release of CD34+, CD133+ and CD34+/CD133+ cells from the bone marrow seems to be
      regulated differently. Modulating the releasing process in CHF may be a tool in
      CHF treatment.

PMID- 19380282
TI  - Determinants of Exocrine Pancreatic Function as Measured by Fecal Elastase-1
      Concentrations (FEC) in Patients with Diabetes mellitus.
AB  - OBJECTIVE: Recently it has been shown that there is not only endocrine
      insufficiency in diabetic patients, but a frequent co-morbidity of both, the
      endocrine and exocrine pancreas. The present study was performed to further
      analyse the determinants of exocrine pancreatic function in patients with
      diabetes mellitus. METHODS: The records of 1992 patients with diabetes mellitus
      who had been treated in our hospital during a 2-year period were re-evaluated.
      Defined parameters were documented in standardized data sheets. Records were
      further checked for the results of imaging procedures of the pancreas. In 307
      patients FEC had been performed and documented. Only these patients were included
      in further evaluation. RESULTS: FEC was inversely correlated with diabetes
      duration and HbA1c-levels but not with age. C-peptide levels correlated
      positively with FEC. BMI and FEC were also significantly correlated. There was no
      correlation between diabetes therapy and exocrine pancreatic function as there
      was no correlation with any concomitant medication. The presence of diabetes
      associated antibodies was not related to FEC. According to the documented data 38
      were classified as type-1 diabetes (12.4%), 167 as type-2 (54.4%), and 88
      patients met the diagnostic criteria of type-3 (28.7%). Fourteen patients could
      not be classified because of lacking information (4.6%). CONCLUSIONS: Exocrine
      insufficiency might be explained as a complication of diabetes mellitus. However,
      it is more likely that type-3 diabetes is much more frequent than previously
      believed. Consequently the evaluation of exocrine function and morphology should
      be included into the clinical workup of any diabetic patient at least at the time
      of manifestation.

PMID- 19380283
TI  - Effects of maleimide-polyethylene glycol-modified human hemoglobin (MP4) on
      tissue necrosis in SKH1-hr hairless mice.
AB  - OBJECTIVE: Tissue hypoxia after blood loss, replantation and flap reperfusion
      remains a challenging task in surgery. Normovolemic hemodilution improves
      hemorheologic properties without increasing oxygen carrying capacity. Red blood
      cell transfusion is the current standard of treatment with its attendant risks.
      The aim of this study was to investigate the potential of the chemically modified
      hemoglobin, MP4, to reduce skin flap necrosis and its effect on selected blood
      markers and kidneys. MATERIALS AND METHODS: Tissue ischemia was induced in the
      ear of hairless mice (n=26). Hemodilution was performed by replacing one third of
      blood volume with the similar amount of MP4, dextran, or blood. The extent of non
      perfused tissue was assessed by intravital fluorescent microscopy. RESULTS: Of
      all groups, MP4 showed the smallest area of no perfusion (in percentage of the
      ear +/- SEM: 16.3% +/- 2.4), the control group the largest (22.4% +/- 3.5).
      Leukocytes showed a significant increase in the MP4 and dextran group (from 8.7
      to 13.6 respectively 15.4*109/l). On histology no changes of the kidneys could be
      observed. CONCLUSION: MP4 causes an increase of leukocytes, improves the oxygen
      supply of the tissue and shows no evidence of renal impairment.

PMID- 19380284
TI  - Systemic inflammatory mediators in post-traumatic complex regional pain syndrome
      (CRPS I) - longitudinal investigations and differences to control groups.
AB  - OBJECTIVES: The Complex Regional Pain Syndrome I (CRPS I) is a disease that might
      affect an extremity after trauma or operation. The pathogenesis remains yet
      unclear. It has clinical signs of severe local inflammation as a result of an
      exaggerated inflammatory response but neurogenic dysregulation also contributes
      to it. Some studies investigated the role inflammatory mediators and cytokines;
      however, few longitudinal studies exist and control groups except healthy
      controls were not investigated yet. METHODS: To get further insights into the
      role of systemic inflammatory mediators in CRPS I, we investigated a variety of
      pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP),
      White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon
      gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II,
      soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide
      (CGRP) at different time points in venous blood from patients with acute (AC) and
      chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE),
      and from healthy volunteers (C). RESULTS: No significant changes for serum
      parameters investigated in CRPS compared to control groups were found except for
      CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II
      p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra-
      or interindividual correlation of parameters with clinical course (e.g.
      chronification) or outcome was detectable. CONCLUSION: Although clinically
      appearing as inflammation in acute stages, local rather than systemic
      inflammatory responses seem to be relevant in CRPS. Variable results from
      different studies might be explained by unpredictable intermittent release of
      mediators from local inflammatory processes into the blood combined with high
      interindividual variabilities. A clinically relevant difference to various
      control groups was not notable in this pilot study. Determination of systemic
      inflammatory parameters is not yet helpful in diagnostic and follow-up of CRPS I.

PMID- 19380285
TI  - Efficacy and safety of darunavir and etravirine in an antiretroviral multi
      experienced youth with vertically HIV-1 infection.
AB  - Multiclass-drug resistance, often caused by poor treatment compliance, is a
      challenging problem in all categories of HIV-infected patients. Selective
      pressure is higher in youth for both biological and behavioral reasons. We report
      the case of a 15-year-old Caucasian male, with vertically acquired HIV-1
      infection, who failed several lines of antiretroviral therapy and was
      successfully treated with darunavir/ritonavir and etravirine.

PMID- 19380286
TI  - HIV or HIV-therapy? Causal attributions of symptoms and their impact on treatment
      decisions among women and men with HIV.
AB  - OBJECTIVES: Among people with HIV, we examined symptom attribution to HIV or HIV
      therapy, awareness of potential side effects and discontinuation of treatment, as
      well as sex/gender differences. METHODS: HIV-patients (N=168, 46% female)
      completed a comprehensive symptom checklist (attributing each endorsed symptom to
      HIV, HIV-therapy, or other causes), reported reasons for treatment
      discontinuations and potential ART-related laboratory abnormalities. RESULTS:
      Main symptom areas were fatigue/sleep/energy, depression/mood, lipodystrophy, and
      gastrointestinal, dermatological, and neurological problems. Top HIV-attributed
      symptoms were lack of stamina/energy in both genders, night sweats, depression,
      mood swings in women; and fatigue, lethargy, difficulties concentrating in men.
      Women attributed symptoms less frequently to HIV than men, particularly fatigue
      (p<.01). Top treatment-attributed symptoms were lipodystrophy and
      gastrointestinal problems in both genders. Symptom attribution to HIV-therapy did
      not differ between genders. Over the past six months, 22% switched/interrupted
      ART due to side effects. In women, side effect-related treatment decisions were
      more complex, involving more side effects and substances. Remarkably, women took
      predominantly protease inhibitor-sparing regimens (p=.05). Both genders reported
      only 15% of potential ART-related laboratory abnormalities but more than 50% had
      laboratory abnormalities. Notably, women had fewer elevated renal parameters
      (p<.01). CONCLUSIONS: Men may attribute symptoms more often to HIV and maintain a
      treatment-regimen despite side effects, whereas women may be more prudent in
      avoiding treatment side effects. Lacking awareness of laboratory abnormalities in
      both genders potentially indicates gaps in physician-patient communication.
      Gender differences in causal attributions of symptoms/side effects may influence
      treatment decisions.

PMID- 19380287
TI  - Proinflammatory and prothrombotic effects on human vascular endothelial cells of
      immune-cell-derived LIGHT.
AB  - OBJECTIVE: LIGHT (TNFSF 14) belongs to the tumor necrosis factor superfamily and
      is expressed by activated T cells as well as various types of antigen presenting
      cells. LIGHT binds to its cellular receptors TR2 and LTbetaR and has a co
      stimulatory role in T cell activation. Here, we compared the relative expression
      of LIGHT in different immune cells and the biological activity of immune cell
      derived LIGHT on endothelial cells. METHODS AND RESULTS: Surface expression of
      LIGHT and mRNA production by PBMC and isolated T cells (CD4+ or CD8+)
      significantly increased after stimulation with PMA (Phorbolester-12- Myristat-13
      Acetat)+ionomycin. No LIGHT expression on PMA stimulated monocytes or monocytic
      like THP-1 cells could be detected; differentiation of monocytes and THP-1 cells
      into macrophages, however, resulted in up-regulation of LIGHT. Supernatants of
      stimulated T cells contained higher concentrations of soluble LIGHT than
      macrophage supernatants normalized to cell numbers; release of soluble LIGHT was
      found to be dependent on metalloproteinase activity. Size determination of
      released soluble LIGHT by size exclusion chromatography revealed a molecular mass
      of approximately 60 kDa, suggesting a trimeric form. Released soluble LIGHT
      induced expression of proinflammatory antigens ICAM-1, tissue factor and IL-8 in
      human endothelial cells and caused apoptosis of IFN-g pretreated endothelial
      cells. Soluble LIGHT was detected at low levels in sera of healthy controls and
      was significantly enhanced in sera of patients with chronic hepatitis C and
      rheumatoid arthritis (24.93+/-9.41 vs. 129.53+/-49.14 and 172.13+/-77.64;
      p<0.0005). CONCLUSION: These findings suggest that among immune cells activated T
      lymphocytes are the main source of soluble LIGHT with released amounts of soluble
      LIGHT markedly higher compared to platelets. Immune cell-derived membrane-bound
      and soluble trimeric LIGHT is biologically active, inducing proinflammatory
      changes in endothelial cells. Enhanced plasma levels of soluble LIGHT in patients
      with chronic infections suggest a role of LIGHT in systemic inflammatory
      activation.

PMID- 19380288
TI  - Gait patterns after intraarticular treatment of patients with osteoarthritis of
      the knee--hyaluronan versus triamcinolone: a prospective, randomized,
      doubleblind, monocentric study.
AB  - OBJECTIVE: Evaluation of gait performance and muscle activity patterns as well as
      clinical efficacy and safety after single intraarticular injection with
      hyaluronan compared with triamcinolone in patients with knee osteoarthritis.
      MATERIALS AND METHODS: This trial evaluated the influence of a single injection
      of hyaluronan or triamcinolone on gait pattern and muscle activity. For clinical
      evaluation a visual analogue scale for pain, Lequesne index, and Knee Society
      Score were used. Quality of life was assessed with the SF-36. RESULTS: The
      complete analysis was performed in 50 of 60 patients. 26 patients were treated
      with triamcinolone and 24 with hyaluronan. Hyaluronan treatment led to
      significant improvement of range of motion at hip and knee. Significant
      improvement could be either demonstrated for the pain scale, Lequesne and Knee
      Society score in both groups. Quality of life showed greater improvement in the
      triamcinolone group. CONCLUSION: Single application of high-viscosity hyaluronan
      shows superior range of motion and pain reduction as well as improvement in
      clinical results. Even if there was a lack of significant differences compared to
      triamcinolone, this therapy classified as safe and effective in the short follow
      up.

PMID- 19380289
TI  - Surgical management of splenic echinococcal disease.
AB  - BACKGROUND: Infection of the spleen with echinococcus is a rare clinical entity.
      Because the diagnosis of a splenic infestation with echinococcus is sometimes
      delayed, large hydatid cysts or pseudotumors may develop, demanding a
      differential surgical approach to cure the disease. METHODS: In a retrospective
      study 10 patients out of 250 with abdominal echinococcosis (4%) were identified
      to have splenic infestation, either limited to the spleen (n=4) or with
      synchronous involvement of the liver (n=4), major omentum (n=1), or the liver and
      lung (n=1). Only one patient had alveolar echinococcosis whereas the others
      showed hydatid cysts of the spleen. Surgical therapy included splenectomy in 7
      patients or partial cyst excision combined with omentoplasty in 3 patients. In
      case of liver involvement, pericystectomy was carried out simultaneously.
      RESULTS: There was no mortality. Postoperative complications were observed in 4
      patients. Hospital stay and morbidity were not influenced when splenic procedures
      were combined with pericystectomies of the liver. Mean follow-up was 8.8 years
      and all of the patients are free of recurrence at this time. CONCLUSIONS:
      Splenectomy should be the preferred treatment of hydatid cysts but partial
      cystectomy is suitable when the cysts are located at the margins of the spleen.
      Due to low morbidity rates, simultaneous treatment of splenic and liver hydatid
      cysts is recommended.

PMID- 19380290
TI  - Validation of the brief multidimensional life satisfaction scale in patients with
      chronic diseases.
AB  - OBJECTIVE: We intended to determine the reliability of a brief life satisfaction
      scale in a sample of patients with chronic diseases, and to analyze its external
      validity. METHODS: Reliability and factor analysis of the 8-item "Brief
      Multidimensional Life Satisfaction Scale" (BMLSS) were performed according to
      standard procedures. The test sample contained 979 individuals (mean age 54+/-11
      years). Forty-two percent had cancer, 22% chronic pain conditions, 10% depressive
      disorders, 6% other chronic diseases, and 20% were healthy. RESULTS: Reliability
      analysis of the 8-item pool revealed a good internal consistency coefficient
      (Cronbach's alpha=.869), and a single-factor structure which explains 53% of
      variance. The BMLSS sum scores significantly differed with respect to the
      underlying disease, family status, duration of disease, and age. The highest
      scores were found in healthy individuals, and the lowest in patients with chronic
      pain conditions and depressive disorders. In cancer patients, the BMLSS
      correlated negatively with Depression/Anxiety (HADS), Fatigue (CFS-D), and
      positively with SF-12's mental health and to a weaker content also with physical
      health. Stepwise regression analyses revealed that life satisfaction can be
      predicted best by (the absence of) depression, but also by Conscious Living
      (AKU), which is an active cognitive-behavioral style in terms of adaptive coping.
      CONCLUSIONS: The evaluation of the BMLSS revealed that the instrument has good
      psychometric properties and can be regarded as a brief, reliable and valid
      measure of LS in patients with chronic diseases. The instrument can be an
      important additive to existing health-related quality of life questionnaires,
      since it captures dimensions that contribute to quality of life but are not
      health related.

PMID- 19380291
TI  - The dark side of the moon: impact of moon phases on long-term survival, mortality
      and morbidity of surgery for lung cancer.
AB  - OBJECTIVE: Superstition is common and causes discomfiture or fear, especially in
      patients who have to undergo surgery for cancer. One superstition is, that moon
      phases influence surgical outcome. This study was performed to analyse lunar
      impact on the outcome following lung cancer surgery. METHODS: 2411 patients
      underwent pulmonary resection for lung cancer in the past 30 years at our
      institution. Intra- and postoperative complications as well as long-term follow
      up data were entered in our lung-cancer database. Factors influencing mortality,
      morbidity and survival were analyzed. RESULTS: Rate of intra-operative
      complications as well as rate of post-operative morbidity and mortality was not
      significantly affected by moon phases. Furthermore, there was no significant
      impact of the lunar cycle on long-term survival. CONCLUSION: In this study there
      was no evidence that outcome of surgery for lung cancer is affected by the moon.
      These results may help the physician to quiet the mind of patients who are
      somewhat afraid of wrong timing of surgery with respect to the moon phases.
      However, patients who strongly believe in the impact of moon phase should be
      taken seriously and correct timing of operations should be conceded to them as
      long as key-date scheduling doesn't constrict evidence based treatment regimens.

PMID- 19380292
TI  - Coinheritance of hereditary spherocytosis and reversibility of cirrhosis in a
      young female patient with hereditary hemochromatosis.
AB  - Here we report a 33-years-old woman with hereditary spherocytosis and
      hemochromatosis due to homozygosity for the C282Y mutation of the HFE gene. The
      coinheritance of both conditions led to severe iron overload and liver cirrhosis
      at young age. The patient was treated by repeated phlebotomy, and reversibility
      of cirrhosis was documented by transient elastography. This report discusses the
      pathophysiology of iron accumulation in patients with hemolytic anemia combined
      with HFE C282Y homozygosity. The case indicates that patients with hematological
      disorders characterized by increased erythropoetic activity should be screened
      for HFE mutations.

PMID- 19380293
TI  - Continuing medical education (CME) or continuing professional development (CPD):
      a need, a challenge, but also a must.

PMID- 19380294
TI  - Vegetal memory.

PMID- 19380295
TI  - Genetic alterations in chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL), the commonest form of leukaemia in adults in
      Western countries, is a genetically heterogeneous disease. The most frequent
      genetic alterations are deletions in 13q14, 17p13 (TP53) and 11q22-q23 (ATM), and
      trisomy of chromosome 12. Furthermore, additional alterations have been
      described. The most relevant techniques used for detection of genetic alterations
      in CLL include comparative genomic hybridisation (CGH) and fluorescence in situ
      hybridisation (FISH). Recently, PCR-based techniques, such as multiplex ligation-
      dependent probe amplification (MLPA), have been used to detect genetic
      alterations in CLL. This review summarises the genetic alterations described in
      CLL and the techniques used for their detection.

PMID- 19380296
TI  - Hedgehog signalling as a target in cancer stem cells.
AB  - Hedgehog (Hh) is one of the most important signalling pathways. Together with the
      Wnt, TGF-Beta/BMP and Notch pathways, it is involved in both embryonic
      development and adult tissue homeostasis. This is because Hh plays a central role
      in the proliferative control and differentiation of both embryonic stem cells and
      adult stem cells. In this way, an alteration in the Hh pathway, either by
      misexpression of components of that pathway or by changes in the expression of
      other cellular components that interfere with the Hh signalling system, may
      trigger the development of several types of cancer. This occurs because normal
      stem cells or their intermediaries toward differentiated mature cells are not
      part of the normal proliferative/ differentiation balance and begin to expand
      without control, triggering the generation of the so-called cancer stem cells. In
      this review, we will focus on the molecular aspects and the role of Hh signalling
      in normal tissues and in tumour development.

PMID- 19380297
TI  - Genetically modified animal models recapitulating molecular events altered in
      human hepatocarcinogenesis.
AB  - New advancements have been made in recent years in the understanding of the
      molecular mechanisms that govern human liver tumorigenesis. Experimental animal
      models have been widely used, especially mouse models. In this review we
      highlight some of the genetically engineered mouse models that have proved to be
      excellent tools to study the intracellular signalling pathways altered in
      hepatocarcinogenesis and establish potential correlations with data from humans,
      with special focus on hepatocellular carcinoma (HCC), the most common type of
      primary liver cancer. Information obtained from these animal models will help to
      design future therapeutic approaches to HCC, particularly those that explore
      drugs that specifically target the altered molecular pathways.

PMID- 19380298
TI  - Pralatrexate, a new hope for aggressive T-cell lymphomas?
AB  - Aggressive T-cell lymphomas represent a particularly poor-prognosis subgroup of
      lymphomas. This is especially true for patients with recurrent or refractory
      disease who typically have a limited response to salvage therapy and an extremely
      poor overall survival. There is thus a strong need to develop potentially active
      drugs for these malignancies. Pralatrexate is a novel antifolate designed to have
      high affinity for the reduced folate carrier type 1. Preclinical and clinical
      studies have demonstrated that pralatrexate has significant activity against T
      cell lymphomas.The dose-limiting toxicity for pralatrexate is mucositis,which
      could be abrogated with folic acid and vitamin B12 supplementation. Pralatrexate
      is now being evaluated in phase II clinical trials for the treatment of
      peripheral T-cell lymphoma, and in a phase I/II trial in combination with
      gemcitabine for the treatment of non-Hodgkin's lymphoma. Because of the limited
      therapies available for aggressive T-cell lymphoma, pralatrexate could secure a
      niche for the treatment of this condition, provided on going clinical trials and
      future phase III trials confirm the efficacy of the drug.

PMID- 19380300
TI  - Screening practice and misplaced priorities.
AB  - PURPOSE: To estimate cancer screening coverage among a large sample of Greek
      individuals. METHODS: 7012 adults from 30 Hellenic areas were surveyed. Tests
      included: faecal occult blood test, sigmoidoscopy,chest X-ray, urine test,
      testicular examination,trans-rectal ultrasound, full blood count, skin
      examination,digital rectal examination, PSA, Pap test, mammography,clinical
      breast examination (CBE), self breast examination and breast ultrasound. RESULTS:
      Eighty-eight percent of males and 93% of females declared being interested in
      cancer screening; 37.8% of men and 37.9% of women had had a medical consultation
      for screening purpose in the previous 2 years. Less than 2%reported having
      received screening for colorectal cancer or skin malignancies. Screening for
      cervical cancer, mammography and CBE was reported by 39.6%, 22.8% and 27.9% of
      females respectively. Twenty percent of males reported screening for prostate
      cancer. CONCLUSION: The actual opportunistic screening approach presents
      important deficiencies with displaced priorities in test performance and a low
      proportion of individuals undergoing recommended tests.

PMID- 19380301
TI  - The EORTC cancer in-patient satisfaction with care questionnaire: EORTC IN
      PATSAT32 Validation study for Spanish patients.
AB  - OBJECTIVES: The EORTC Quality of Life (QL) Group has developed a questionnaire
      (the EORTC IN-PATSAT32) to assess the satisfaction of cancer inpatients with
      hospitalbased care. In this study we assess the psychometric properties of the
      EORTC IN-PATSAT32 applied to a sample of Spanish patients. MATERIALS AND METHODS:
      Eighty cancer patients with different tumour sites completed the EORTC QLQ-C30
      and EORTC IN-PATSAT32 questionnaires. Psychometric evaluation of the structure,
      reliability and validity was conducted. RESULTS: Multitrait scaling analysis
      showed that most itemscale correlation coefficients met the standards of
      convergent and discriminant validity. Cronbach's coefficients were good (0.77
      0.97) for all scales except hospital access. Correlations between the scales and
      single items of the QLQ-C30 and EORTC IN-PATSAT32 were generally low.
      Correlations between the Oberst scales and an item on intention to recommend the
      hospital or ward to others with the EORTC IN-PATSAT32 were moderate. Patients
      with higher scores on the Oberst scales and the item on intention to recommend
      the hospital or ward showed higher satisfaction with care levels in all EORTC IN
      PATSAT32 areas but one. CONCLUSIONS: The EORTC IN-PATSAT32 appears to be a
      reliable and valid instrument when applied to a sample of Spanish cancer
      patients. These results are in line with those of the EORTC validation study.

PMID- 19380299
TI  - Epidemiologic study to assess patient involvement in choice of adjuvant
      chemotherapy for breast cancer (PROSA Study).
AB  - INTRODUCTION: The objective of the current study was to assess patient
      involvement in adjuvant chemotherapy choice, reasons for treatment choice and
      satisfaction with the chosen treatment, given that improvement in breast cancer
      survival has been accompanied by a greater demand for disease information from
      patients. MATERIAL AND METHODS: An epidemiologic, prospective, multicentre study
      was conducted with patients aged over 18 diagnosed with breast cancer stages I,
      II and III. The study, which was conducted prior to these patients initiating
      adjuvant chemotherapy, was based on a baseline visit and a follow-up visit. Data
      on sociodemographic and clinical variables were collected and a survey was
      administered to assess both the reasons for choosing particular treatments and
      ultimate satisfaction with the chosen treatment. Statistical procedures included
      a descriptive analysis, bivariate tests and logistic regression. RESULTS: A total
      of 613 patients were recruited with a mean (SD) age of 53.3 (10.8) years. Most
      patients had stage II breast cancer (53.9%) and an Eastern Cooperative Oncology
      Group (ECOG) performance status of 0 (82.8%). Of these patients, 58.3% were
      treated with taxanes (48.2% docetaxel, doxorubicin and cyclophosphamide) and
      41.7% without (43.5% 5-fluorouracil, epirubicin and cyclophosphamide). At the
      baseline visit and final visit, 73.8% and 72.6% of patients, respectively, were
      aware of their diagnosis and prognosis. A total of 77.1% patients (64.7% who had
      followed their physician's advice) were involved in treatment choice and this
      involvement was directly related to improved ECOG performance status and
      information. A total of 78.7% of patients were very satisfied or satisfied with
      their treatment and 5.4% of patients refused to continue treatment (with 39.3%
      giving toxicity as the reason). CONCLUSIONS: Although a high proportion of
      patients were involved in choosing their treatment, this involvement was not
      related to greater treatment satisfaction. Further research in routine clinical
      settings is needed in order to assess other factors related to choice of adjuvant
      chemotherapy, treatment satisfaction and long-term effectiveness (3-5 years).

PMID- 19380302
TI  - Chemopreventive efficacies of rosiglitazone, fenretinide and their combination
      against rat mammary carcinogenesis.
AB  - INTRODUCTION: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and
      retinoic acid receptors (RAR/RXR) belong to the nuclear steroid receptor family.
      In vitro studies have suggested that PPAR-gamma ligands are highly effective in
      preventing mammary tumours and these effects are enhanced by some retinoids.
      However, in vivo anti-initiator and anti-promoter efficacies of this combination
      are not clear. AIM AND METHODS: The present study aimed to investigate the
      chemopreventive efficacies of the PPAR-gamma ligand rosiglitazone (200
      microg/kg/day), synthetic retinoid fenretinide (0.3 mg/kg/day) and their
      combination on a DMBA-induced rat mammary carcinogenesis model. RESULTS: In the
      rosiglitazone group, no malignant tumour developed, apart from the lowest
      proliferative mammary lesions. In the fenretinide group, 30% developed a
      malignant tumour but there were no benign tumours. Cancer incidences were 61.5%
      and 10% in the control and combination groups respectively. CONCLUSIONS: Our
      results showed that the PPAR-gamma ligand rosiglitazone and synthetic retinoid
      fenretinide have potent chemopreventive properties against in vivo mammary
      carcinogenesis; however, the efficacies were not enhanced by their combination.

PMID- 19380303
TI  - Peritoneal solitary fibrous tumour (SFT): long-term survival of recurrent and
      metastasised SFT treated with cytoreductive surgery and intraperitoneal
      chemotherapy.
AB  - This study reports a case of a SFT of the peritoneum in a 44-year-old white man
      that recurred 3 years after the initial surgical removal of the tumour. The
      patient recurred diffusely, developing a pattern of sarcomatosis and hepatic
      metastasis and was treated by surgical cytoreduction followed by intraoperative
      peritoneal hyperthermic chemotherapy (IPHC). Subsequently, he developed pulmonary
      metastases and was treated with palliative chemotherapy. The patient persisted
      with recurrent and distant disease, although it was reduced and stabilised,
      allowing his survival for the last 3 years since the extended surgery. New
      treatment strategies for a rare disease such as this one have first to be
      described in order to improve patient follow-up.

PMID- 19380304
TI  - Retroperitoneal tumour radiotherapy: clinical improvements using kilovoltage cone
      beam computed tomography.
AB  - We present a clinical case of a patient diagnosed with a retroperitoneal sarcoma,
      which received preoperative treatment with daily verification via computed
      tomography obtained with kilovoltage cone beam. We compare the benefit of this
      treatment compared to other conventional treatment without image guiding,
      reporting quantitative results.

PMID- 19380305
TI  - Synchronous isolated adrenal metastasis from rectum adenocarcinoma.

PMID- 19380306
TI  - Pinacidil induces vascular dilation and hyperemia in vivo and does not impact
      biophysical properties of neurons and astrocytes in vitro.
AB  - Vascular and neural systems are highly interdependent, as evidenced by the wealth
      of intrinsic modulators shared by the two systems. We tested the hypothesis that
      pinacidil, a selective agonist for the SUR2B receptor found on smooth muscles,
      could serve as an independent means of inducing vasodilation and increased local
      blood volume to emulate functional hyperemia. Application of pinacidil induced
      vasodilation and increased blood volume in the in vivo neocortex in anesthetized
      rats and awake mice. Direct application of this agent to the in vitro neocortical
      slice had no direct impact on biophysical properties of neurons or astrocytes
      assessed with whole-cell recording. These findings suggest that pinacidil
      provides an effective and selective means for inducing hyperemia in vivo, and may
      provide a useful tool in directly testing the impact of hemodynamics on neural
      activity, as recently predicted by the hemo-neural hypothesis.

PMID- 19380307
TI  - Concurrent dual allergen exposure and its effects on airway hyperresponsiveness,
      inflammation and remodeling in mice.
AB  - Experimental mouse models of asthma have broadened our understanding of the
      mechanisms behind allergen-induced asthma. Typically, mouse models of allergic
      asthma explore responses to a single allergen; however, patients with asthma are
      frequently exposed to, and tend to be allergic to, more than one allergen. The
      aim of the current study was to develop a new and more relevant mouse model of
      asthma by measuring the functional, inflammatory and structural consequences of
      chronic exposure to a combination of two different allergens, ovalbumin (OVA) and
      house dust mite (HDM), in comparison with either allergen alone. BALB/c mice were
      sensitized and exposed to OVA, HDM or the combination of HDM and OVA for a period
      of 10 weeks. Following allergen exposure, airway responsiveness was measured
      using the flexiVent small animal ventilator, and mice were assessed for indices
      of airway inflammation and remodeling at both 24 hours and 4 weeks after the
      final allergen exposure. Mice exposed to the HDM-OVA combination exhibited
      increased numbers of inflammatory cells in the bronchoalveolar lavage (BAL) when
      compared with mice exposed to a single allergen. Mice exposed to HDM-OVA also
      exhibited an elevated level of lung tissue mast cells compared with mice exposed
      to a single allergen. Following the resolution of inflammatory events, mice
      exposed to the allergen combination displayed an elevation in the maximal degree
      of total respiratory resistance (Max R(RS)) compared with mice exposed to a
      single allergen. Furthermore, trends for increases in indices of airway
      remodeling were observed in mice exposed to the allergen combination compared
      with a single allergen. Although concurrent exposure to HDM and OVA resulted in
      increased aspects of airway hyperresponsiveness, airway inflammation and airway
      remodeling when compared with exposure to each allergen alone, concurrent
      exposure did not result in a substantially more robust mouse model of allergic
      asthma than exposure to either allergen alone.

PMID- 19380308
TI  - Ethanol induces embryonic malformations by competing for retinaldehyde
      dehydrogenase activity during vertebrate gastrulation.
AB  - Human embryos exposed to alcohol (ethanol) develop a complex developmental
      phenotype known as fetal alcohol spectrum disorder (FASD). In Xenopus embryos,
      ethanol reduces the levels of retinoic acid (RA) signaling during gastrulation.
      RA, a metabolite of vitamin A (retinol), is required for vertebrate
      embryogenesis, and deviation from its normal levels results in developmental
      malformations. Retinaldehyde dehydrogenase 2 (RALDH2) is required to activate RA
      signaling at the onset of gastrulation. We studied the effect of alcohol on
      embryogenesis by manipulating retinaldehyde dehydrogenase activity in ethanol
      treated embryos. In alcohol-treated embryos, we analyzed RA signaling levels,
      phenotypes induced and changes in gene expression. Developmental defects that
      were characteristic of high ethanol concentrations were phenocopied by a low
      ethanol concentration combined with partial RALDH inhibition, whereas Raldh2
      overexpression rescued the developmental malformations induced by high ethanol.
      RALDH2 knockdown resulted in similar RA signaling levels when carried out alone
      or in combination with ethanol treatment, suggesting that RALDH2 is the main
      target of ethanol. The biochemical evidence that we present shows that, at the
      onset of RA signaling during early gastrulation, the ethanol effect centers on
      the competition for the available retinaldehyde dehydrogenase activity. In light
      of the multiple regulatory roles of RA, continued embryogenesis in the presence
      of abnormally low RA levels provides an etiological explanation for the
      malformations observed in individuals with FASD.

PMID- 19380310
TI  - A new optical low coherence reflectometry device for ocular biometry in cataract
      patients.
AB  - BACKGROUND: A new commercially available optical low coherence reflectometry
      device (Lenstar, Haag-Streit or Allegro Biograph, Wavelight) provides high
      resolution non-contact measurements of ocular biometry. The study evaluates the
      validity and repeatability of these measurements compared with current clinical
      instrumentation. METHOD: Measurements were taken with the LenStar and IOLMaster
      on 112 patients aged 41-96 years listed for cataract surgery. A subgroup of 21
      patients also had A-scan applanation ultrasonography (OcuScan) performed.
      Intersession repeatability of the LenStar measurements was assessed on 32
      patients. RESULTS: LenStar measurements of white-to-white were similar to the
      IOLMaster (average difference 0.06 (SD 0.03) D; p = 0.305); corneal curvature
      measurements were similar to the IOLMaster (average difference -0.04 (0.20) D; p
      = 0.240); anterior chamber depth measurements were significantly longer than the
      IOLMaster (by 0.10 (0.40) mm) and ultrasound (by 0.32 (0.62) mm; p<0.001);
      crystalline lens thickness measurements were similar to ultrasound (difference
      0.16 (0.83) mm, p = 0.382); axial length measurements were significantly longer
      than the IOLMaster (by 0.01 (0.02) mm) but shorter than ultrasound (by 0.14
      (0.15) mm; p<0.001). The LensStar was unable to take measurements due to dense
      media opacities in a similar number of patients to the IOLMaster (9-10%). The
      LenStar biometric measurements were found to be highly repeatable (variability <
      or = 2% of average value). CONCLUSIONS: Although there were some statistical
      differences between ocular biometry measurements between the LenStar and current
      clinical instruments, they were not clinically significant. LenStar measurements
      were highly repeatable and the instrument easy to use.

PMID- 19380309
TI  - Inactivation of Drosophila Huntingtin affects long-term adult functioning and the
      pathogenesis of a Huntington's disease model.
AB  - A polyglutamine expansion in the huntingtin (HTT) gene causes neurodegeneration
      in Huntington's disease (HD), but the in vivo function of the native protein
      (Htt) is largely unknown. Numerous biochemical and in vitro studies have
      suggested a role for Htt in neuronal development, synaptic function and axonal
      trafficking. To test these models, we generated a null mutant in the putative
      Drosophila HTT homolog (htt, hereafter referred to asdhtt) and, surprisingly,
      found that dhtt mutant animals are viable with no obvious developmental defects.
      Instead, dhtt is required for maintaining the mobility and long-term survival of
      adult animals, and for modulating axonal terminal complexity in the adult brain.
      Furthermore, removing endogenous dhtt significantly accelerates the
      neurodegenerative phenotype associated with a Drosophila model of polyglutamine
      Htt toxicity (HD-Q93), providing in vivo evidence that disrupting the normal
      function of Htt might contribute to HD pathogenesis.

PMID- 19380311
TI  - Assessing the performance of the Whisperflow continuous positive airway pressure
      generator: a bench study.
AB  - BACKGROUND: There are few data describing the performance of the Whisperflow
      continuous positive airway pressure (CPAP) generator. METHODS: (i) (a) A static
      test of 11 Whisperflow devices examining maximum flow generation with no load and
      with 2.5, 5, 7.5, 10, 15, and 20 cm H2O valve loading, at varying Fi(O2). (b)
      CPAP valves (Accu-peep(R), Vital Signs, Totowa, NJ, USA) were tested by measuring
      mean upstream pressure at varying flows in five valves (2.5, 5, 7.5, 10, 15, and
      20 cm H2O). (ii) We measured the mean and minimum inspiratory mask pressure
      generated by a representative Whisperflow device in a model of spontaneous
      respiration. Measurements were made with combinations of Fi(O2), ventilatory
      frequency, tidal volume, and valve loading similar to those encountered in
      clinical practice. RESULTS: (i) (a) The flow generated by the Whisperflow valves
      decreases with increasing valve load and increasing Fi(O2) (from 140 to 20 litre
      min(-1)). (b) The CPAP valves maintain the required pressure within acceptable
      limits against varying flow. (ii) At all permutations, the mean inspiratory mask
      pressure was significantly lower than that required. At high inspiratory flow
      rates, the minimum inspiratory pressure approached atmospheric pressure.
      CONCLUSIONS: The Whisperflow may not perform as expected. Clinicians should be
      cautious when using this device, particularly with high Fi(O2) and CPAP valve
      load. The flow setting should be set at maximum. Failure of CPAP therapy may be
      due to failure of the generator. Further in vivo data are required.

PMID- 19380313
TI  - The virtual physiological human: tools and applications I.

PMID- 19380312
TI  - Practical anatomic landmarks for determining the insertion depth of central
      venous catheter in paediatric patients.
AB  - BACKGROUND: Various methods have been recommended to decide a proper insertion
      depth of central venous catheter (CVC). The carina is recommended as a useful
      target level for the CVC tip position. We evaluated the sternal head of a right
      clavicle and the nipples as anatomic landmarks for determining the optimal depth
      of CVC in paediatric patients. METHODS: Ninety children, <5 yr, undergoing
      catheterization through the right internal jugular vein were enrolled. The
      insertion depth was determined as follows. The insertion point was designated as
      'Point I'. The sternal head of the right clavicle was called 'Point A' and the
      midpoint of the perpendicular line drawn from Point A to the line connecting both
      nipples was called 'Point B'. The insertion depth of CVC was determined by adding
      the two distances (from I to A and from A to B) and subtracting 0.5 cm from this.
      A chest radiography was taken and the distance of the CVC tip from the carina
      level was measured by the Picture Archiving and Communicating System. RESULTS:
      The mean distance of the CVC tip from the carina level was 0.1 (1.0) (P=0.293) cm
      above the carina (95% CI 0.1 cm below the carina-0.3 cm above the carina). There
      was no specific relationship between the distance of the CVC tip from the carina
      level and the patients' age, height, and weight. CONCLUSIONS: The CVC tip could
      be placed near the carina by using the external landmarks without any formulae,
      images, and devices in children in our study.

PMID- 19380314
TI  - A physiome standards-based model publication paradigm.
AB  - In this era of widespread broadband Internet penetration and powerful Web
      browsers on most desktops, a shift in the publication paradigm for physiome-style
      models is envisaged. No longer will model authors simply submit an essentially
      textural description of the development and behaviour of their model. Rather,
      they will submit a complete working implementation of the model encoded and
      annotated according to the various standards adopted by the physiome project,
      accompanied by a traditional human-readable summary of the key scientific goals
      and outcomes of the work. While the final published, peer-reviewed article will
      look little different to the reader, in this new paradigm, both reviewers and
      readers will be able to interact with, use and extend the models in ways that are
      not currently possible. Here, we review recent developments that are laying the
      foundations for this new model publication paradigm. Initial developments have
      focused on the publication of mathematical models of cellular electrophysiology,
      using technology based on a CellML- or Systems Biology Markup Language (SBML)
      encoded implementation of the mathematical models. Here, we review the current
      state of the art and what needs to be done before such a model publication
      becomes commonplace.

PMID- 19380315
TI  - CellML metadata standards, associated tools and repositories.
AB  - The development of standards for encoding mathematical models is an important
      component of model building and model sharing among scientists interested in
      understanding multi-scale physiological processes. CellML provides such a
      standard, particularly for models based on biophysical mechanisms, and a
      substantial number of models are now available in the CellML Model Repository.
      However, there is an urgent need to extend the current CellML metadata standard
      to provide biological and biophysical annotation of the models in order to
      facilitate model sharing, automated model reduction and connection to biological
      databases. This paper gives a broad overview of a number of new developments on
      CellML metadata and provides links to further methodological details available
      from the CellML website.

PMID- 19380316
TI  - FieldML: concepts and implementation.
AB  - The field modelling language FieldML is being developed as a standard for
      modelling and interchanging field descriptions in software, suitable for a wide
      range of computation techniques. It comprises a rich set of operators for
      defining generalized fields as functions of other fields, starting with basic
      domain fields including sets of discrete objects and coordinate systems. It is
      extensible by adding new operators and by their arbitrary combination in
      expressions, making it well suited for describing the inherent complexity of
      biological materials and organ systems. This paper describes the concepts behind
      FieldML, including a simple example of a spatially varying finite-element field.
      It outlines current implementations in established, open source computation and
      visualization software, both drawing on decades of bioengineering modelling
      software development experience.

PMID- 19380317
TI  - CELLULAR OPEN RESOURCE (COR): current status and future directions.
AB  - The need for tools to aid the description and sharing of biological models was
      highlighted at the launch of the International Union of Physiological Sciences
      Physiome Project in 1997. This has resulted in the release, in 2001, of the
      CellML specifications (http://www.cellml.org/specifications/). CELLULAR OPEN
      RESOURCE (COR) was among the early adopters of this standard, eventually forming
      the first publicly available CellML-based modelling and collaboration
      environment. From the onset, COR was designed to provide an environment that
      could not only be used by experienced modellers, but also by experimentalists,
      teachers and students. It therefore tries to combine a user-friendly interface
      with a computationally efficient numerical engine. In this paper, we introduce
      the philosophy behind COR, explain its user interface and current functionality,
      including the editing and running of CellML files, highlight lessons learned from
      user feedback and problems experienced during the development of COR and conclude
      by exploring future development potential.

PMID- 19380318
TI  - CHASTE: incorporating a novel multi-scale spatial and temporal algorithm into a
      large-scale open source library.
AB  - Recent work has described the software engineering and computational
      infrastructure that has been set up as part of the Cancer, Heart and Soft Tissue
      Environment (CHASTE) project. CHASTE is an open source software package that
      currently has heart and cancer modelling functionality. This software has been
      written using a programming paradigm imported from the commercial sector and has
      resulted in a code that has been subject to a far more rigorous testing procedure
      than that is usual in this field. In this paper, we explain how new functionality
      may be incorporated into CHASTE. Whiteley has developed a numerical algorithm for
      solving the bidomain equations that uses the multi-scale (MS) nature of the
      physiology modelled to enhance computational efficiency. Using a simple geometry
      in two dimensions and a purpose-built code, this algorithm was reported to give
      an increase in computational efficiency of more than two orders of magnitude. In
      this paper, we begin by reviewing numerical methods currently in use for solving
      the bidomain equations, explaining how these methods may be developed to use the
      MS algorithm discussed above. We then demonstrate the use of this algorithm
      within the CHASTE framework for solving the monodomain and bidomain equations in
      a three-dimensional realistic heart geometry. Finally, we discuss how CHASTE may
      be developed to include new physiological functionality--such as modelling a
      beating heart and fluid flow in the heart--and how new algorithms aimed at
      increasing the efficiency of the code may be incorporated.

PMID- 19380320
TI  - Simulation of cardiac electrophysiology on next-generation high-performance
      computers.
AB  - Models of cardiac electrophysiology consist of a system of partial differential
      equations (PDEs) coupled with a system of ordinary differential equations
      representing cell membrane dynamics. Current software to solve such models does
      not provide the required computational speed for practical applications. One
      reason for this is that little use is made of recent developments in adaptive
      numerical algorithms for solving systems of PDEs. Studies have suggested that a
      speedup of up to two orders of magnitude is possible by using adaptive methods.
      The challenge lies in the efficient implementation of adaptive algorithms on
      massively parallel computers. The finite-element (FE) method is often used in
      heart simulators as it can encapsulate the complex geometry and small-scale
      details of the human heart. An alternative is the spectral element (SE) method, a
      high-order technique that provides the flexibility and accuracy of FE, but with a
      reduced number of degrees of freedom. The feasibility of implementing a parallel
      SE algorithm based on fully unstructured all-hexahedra meshes is discussed. A
      major computational task is solution of the large algebraic system resulting from
      FE or SE discretization. Choice of linear solver and preconditioner has a
      substantial effect on efficiency. A fully parallel implementation based on
      dynamic partitioning that accounts for load balance, communication and data
      movement costs is required. Each of these methods must be implemented on next
      generation supercomputers in order to realize the necessary speedup. The problems
      that this may cause, and some of the techniques that are beginning to be
      developed to overcome these issues, are described.

PMID- 19380319
TI  - Numerical solution of the bidomain equations.
AB  - Knowledge of cardiac electrophysiology is efficiently formulated in terms of
      mathematical models. However, most of these models are very complex and thus
      defeat direct mathematical reasoning founded on classical and analytical
      considerations. This is particularly so for the celebrated bidomain model that
      was developed almost 40 years ago for the concurrent analysis of extra- and
      intracellular electrical activity. Numerical simulations based on this model
      represent an indispensable tool for studying electrophysiology. However, complex
      mathematical models, steep gradients in the solutions and complicated geometries
      lead to extremely challenging computational problems. The greatest achievement in
      scientific computing over the past 50 years has been to enable the solving of
      linear systems of algebraic equations that arise from discretizations of partial
      differential equations in an optimal manner, i.e. such that the central
      processing unit (CPU) effort increases linearly with the number of computational
      nodes. Over the past decade, such optimal methods have been introduced in the
      simulation of electrophysiology. This development, together with the development
      of affordable parallel computers, has enabled the solution of the bidomain model
      combined with accurate cellular models, on geometries resembling a human heart.
      However, in spite of recent progress, the full potential of modern computational
      methods has yet to be exploited for the solution of the bidomain model. This
      paper reviews the development of numerical methods for solving the bidomain
      model. However, the field is huge and we thus restrict our focus to developments
      that have been made since the year 2000.

PMID- 19380321
TI  - Robust modelling, measurement and analysis of human and animal metabolic systems.
AB  - Modelling human and animal metabolism is impeded by the lack of accurate
      quantitative parameters and the large number of biochemical reactions. This
      problem may be tackled by: (i) study of modules of the network independently;
      (ii) ensemble simulations to explore many plausible parameter combinations; (iii)
      analysis of 'sloppy' parameter behaviour, revealing interdependent parameter
      combinations with little influence; (iv) multiscale analysis that combines
      molecular and whole network data; and (v) measuring metabolic flux (rate of flow)
      in vivo via stable isotope labelling. For the latter method, carbon transition
      networks were modelled with systems of ordinary differential equations, but we
      show that coloured Petri nets provide a more intuitive graphical approach.
      Analysis of parameter sensitivities shows that only a few parameter combinations
      have a large effect on predictions. Model analysis of high-energy phosphate
      transport indicates that membrane permeability, inaccurately known at the
      organellar level, can be well determined from whole-organ responses. Ensemble
      simulations that take into account the imprecision of measured molecular
      parameters contradict the popular hypothesis that high-energy phosphate transport
      in heart muscle is mostly by phosphocreatine. Combining modular, multiscale,
      ensemble and sloppy modelling approaches with in vivo flux measurements may prove
      indispensable for the modelling of the large human metabolic system.

PMID- 19380322
TI  - Computer-aided design and finite-element modelling of biomaterial scaffolds for
      bone tissue engineering.
AB  - Scaffold biomaterials for tissue engineering can be produced in many different
      ways depending on the applications and the materials used. Most research into new
      biomaterials is based on an experimental trial-and-error approach that limits the
      possibility of making many variations to a single material and studying its
      interaction with its surroundings. Instead, computer simulation applied to tissue
      engineering can offer a more exhaustive approach to test and screen out
      biomaterials. In this paper, a review of the current approach in biomaterials
      designed through computer-aided design (CAD) and through finite-element modelling
      is given. First we review the approach used in tissue engineering in the
      development of scaffolds and the interactions existing between biomaterials,
      cells and mechanical stimuli. Then, scaffold fabrication through CAD is presented
      and characterization of existing scaffolds through computed images is reviewed.
      Several case studies of finite-element studies in tissue engineering show the
      usefulness of computer simulations in determining the mechanical environment of
      cells when seeded into a scaffold and the proper design of the geometry and
      stiffness of the scaffold. This creates a need for more advanced studies that
      include aspects of mechanobiology in tissue engineering in order to be able to
      predict over time the growth and differentiation of tissues within scaffolds.
      Finally, current perspectives indicate that more efforts need to be put into the
      development of such advanced studies, with the removal of technical limitations
      such as computer power and the inclusion of more accurate biological and genetic
      processes into the developed algorithms.

PMID- 19380323
TI  - In silico biology of bone modelling and remodelling: adaptation.
AB  - Modelling and remodelling are the processes by which bone adapts its shape and
      internal structure to external influences. However, the cellular mechanisms
      triggering osteoclastic resorption and osteoblastic formation are still unknown.
      In order to investigate current biological theories, in silico models can be
      applied. In the past, most of these models were based on the continuum
      assumption, but some questions related to bone adaptation can be addressed better
      by models incorporating the trabecular microstructure. In this paper, existing
      simulation models are reviewed and one of the microstructural models is extended
      to test the hypothesis that bone adaptation can be simulated without particular
      knowledge of the local strain distribution in the bone. Validation using an
      experimental murine loading model showed that this is possible. Furthermore, the
      experimental model revealed that bone formation cannot be attributed only to an
      increase in trabecular thickness but also to structural reorganization including
      the growth of new trabeculae. How these new trabeculae arise is still an
      unresolved issue and might be better addressed by incorporating other levels of
      hierarchy, especially the cellular level. The cellular level sheds light on the
      activity and interplay between the different cell types, leading to the effective
      change in the whole bone. For this reason, hierarchical multi-scale simulations
      might help in the future to better understand the biomathematical laws behind
      bone adaptation.

PMID- 19380324
TI  - In silico biology of bone modelling and remodelling: regeneration.
AB  - Bone regeneration is the process whereby bone is able to (scarlessly) repair
      itself from trauma, such as fractures or implant placement. Despite extensive
      experimental research, many of the mechanisms involved still remain to be
      elucidated. Over the last decade, many mathematical models have been established
      to investigate the regeneration process in silico. The first models considered
      only the influence of the mechanical environment as a regulator of the healing
      process. These models were followed by the development of bioregulatory models
      where mechanics was neglected and regeneration was regulated only by biological
      stimuli such as growth factors. The most recent mathematical models couple the
      influences of both biological and mechanical stimuli. Examples are given to
      illustrate the added value of mathematical regeneration research, specifically in
      the in silico design of treatment strategies for non-unions. Drawbacks of the
      current continuum-type models, together with possible solutions in extending the
      models towards other time and length scales are discussed. Finally, the demands
      for dedicated and more quantitative experimental research are presented.

PMID- 19380325
TI  - A mathematical approach to bone tissue engineering.
AB  - Tissue engineering is becoming consolidated in the biomedical field as one of the
      most promising strategies in tissue repair and regenerative medicine. Within this
      discipline, bone tissue engineering involves the use of cell-loaded porous
      biomaterials, i.e. bioscaffolds, to promote bone tissue regeneration in bone
      defects or diseases such as osteoporosis, although it has not yet been
      incorporated into daily clinical practice. The overall success of a particular
      bone tissue engineering application depends strongly on scaffold design
      parameters, which do away with long and expensive clinical protocols. Computer
      simulation is a useful tool that may reduce animal experiments and help to
      identify optimal patient-specific designs after concise model validation. In this
      paper, we present a novel mathematical approach to bone regeneration within
      scaffolds, based on a multiscale framework. Results are presented over an actual
      scaffold microstructure, showing the potential of computer simulation, and how it
      can aid in the task of making bone tissue engineering a reality in clinical
      practice.

PMID- 19380326
TI  - Multi-level patient-specific modelling of the proximal femur. A promising tool to
      quantify the effect of osteoporosis treatment.
AB  - Preventing femoral fractures is an important goal in osteoporosis research. In
      order to evaluate a person's fracture risk and to quantify response to treatment,
      bone competence is best assessed by bone strength. Finite-element (FE) modelling
      based on medical imaging is considered a very promising technique for the
      assessment of in vivo femoral bone strength. Over the past decades, a number of
      different FE models have been presented focusing on the effect of several
      methodological aspects, such as mesh type, material properties and loading
      conditions, on the precision and accuracy of these models. In this paper, a
      review of this work is presented. We conclude that moderate to good predictions
      can be made, especially when the models are tuned to specific loading scenarios.
      However, there is room for improvement when multiple loading conditions need to
      be evaluated. We hypothesize that including anisotropic material properties is
      the first target. As a proof of the concept, we demonstrate that the main
      orientation of the femoral bone structure can be calculated from clinical
      computed tomography scans. We hypothesize that this structural information can be
      used to estimate the anisotropic bone material properties, and that in the future
      this could potentially lead to a greater predictive value of FE models for
      femoral bone strength.

PMID- 19380327
TI  - Numerical modelling of the shoulder for clinical applications.
AB  - Research activity involving numerical models of the shoulder is dramatically
      increasing, driven by growing rates of injury and the need to better understand
      shoulder joint pathologies to develop therapeutic strategies. Based on the type
      of clinical question they can address, existing models can be broadly categorized
      into three groups: (i) rigid body models that can simulate kinematics, collisions
      between entities or wrapping of the muscles over the bones, and which have been
      used to investigate joint kinematics and ergonomics, and are often coupled with
      (ii) muscle force estimation techniques, consisting mainly of optimization
      methods and electromyography-driven models, to simulate muscular action and joint
      reaction forces to address issues in joint stability, muscular rehabilitation or
      muscle transfer, and (iii) deformable models that account for stress-strain
      distributions in the component structures to study articular degeneration,
      implant failure or muscle/tendon/bone integrity. The state of the art in
      numerical modelling of the shoulder is reviewed, and the advantages, limitations
      and potential clinical applications of these modelling approaches are critically
      discussed. This review concentrates primarily on muscle force estimation
      modelling, with emphasis on a novel muscle recruitment paradigm, compared with
      traditionally applied optimization methods. Finally, the necessary benchmarks for
      validating shoulder models, the emerging technologies that will enable further
      advances and the future challenges in the field are described.

PMID- 19380328
TI  - Growth hormone resistance in severe heart failure resolves after cardiac
      transplantation.
AB  - AIMS: Severe heart failure (HF) is associated with cachexia; this is often
      reversed post cardiac transplantation (HTx) with frequent development of obesity.
      Growth hormone (GH) resistance is common in HF and may contribute to cachexia.
      Whether GH resistance resolves post HTx is unknown. We aimed to confirm that HF
      is associated with GH resistance and to test the hypothesis that GH resistance
      resolves post HTx. METHODS AND RESULTS: We measured GH, insulin-like growth
      factor-1 (IGF-1), and body composition in 10 HF patients awaiting HTx, in 18
      patients 11 +/- 8 months post HTx, and seven controls. Body mass index was 23.5
      +/- 3.2 in HF patients and 29.3 +/- 5.7 post HTx. HTx patients had gained 14 +/-
      8 kg since HTx. GH was elevated in HF (control: 0.21 +/- 0.25; HF: 1.13 +/- 1.19;
      HTx: 0.11 +/- 0.13 ng/mL; P < 0.007), while IGF-1 was higher in HTx (control: 114
      +/- 57; HF: 94 +/- 52; HTx: 190 +/- 106 ng/mL; P < 0.02). HTx had higher total
      body and abdominal fat %. CONCLUSION: GH resistance is present in severe HF and
      resolves post HTx. These findings should be confirmed through larger trials.

PMID- 19380329
TI  - Baseline factors associated with congestive heart failure in patients receiving
      etoricoxib or diclofenac: multivariate analysis of the MEDAL program.
AB  - AIMS: Non-steroidal anti-inflammatory drugs have been associated with increased
      risk of congestive heart failure (CHF). We aimed to assess the impact of
      treatment with etoricoxib or diclofenac on risk of CHF relative to baseline risk
      factors. METHODS AND RESULTS: We performed a multivariate analysis of 34 701
      patients with arthritis receiving etoricoxib 60 or 90 mg, or diclofenac 150 mg,
      daily for a mean of 18 months, to assess the incidence of confirmed, adjudicated
      CHF events resulting in emergency room visit or hospitalization. Analyses were
      performed using a Cox proportional hazard model to evaluate the hazard ratio (HR)
      between the levels of each risk marker for the incidence of CHF. Significant risk
      markers included history of CHF (HR: 6.69, 95% CI 3.59-12.47; P <0.0001), age >
      or = 65 years (2.56, 1.65-3.98; P <0.0001), and history of hypertension (1.83,
      1.16-2.89; P = 0.0094) or diabetes (1.83, 1.15-2.94; P = 0.0116). Etoricoxib vs.
      diclofenac was a significant risk factor only when pooling the etoricoxib 90 mg
      cohorts (1.88; 1.13-3.10; P = 0.0143). Etoricoxib 60 mg did not significantly
      increase risk vs. diclofenac. CONCLUSION: History of CHF was highly associated
      with risk for CHF hospitalization. Hypertension, diabetes, and older age also
      increased risk modestly. There appeared to be a dose-related increase in CHF with
      etoricoxib compared with diclofenac, which reached statistical significance when
      the etoricoxib 90 mg groups (osteoarthritis and rheumatoid arthritis) were
      pooled.

PMID- 19380330
TI  - Health technology assessment and public health: a time for convergence.

PMID- 19380331
TI  - Assisted suicide on TV--the public 'License to Kill'?

PMID- 19380332
TI  - Suicides in public places: findings from one English county.
AB  - Little is known about where suicides take place. We collected data from coroners'
      files on all suicides and undetermined deaths in one large English county from
      2000 to 2004. The data show that >30% of suicides occurred in public places. A
      quarter of these involved jumping from a height and nearly a quarter involved car
      exhaust poisoning. Several sites were associated with multiple methods of
      suicide. Identifying and managing high-risk locations should be an important part
      of an overall suicide prevention strategy and is best tackled at local level.

PMID- 19380333
TI  - Personality and health as predictors of income decrease in old age: findings from
      the longitudinal SMILE study.
AB  - BACKGROUND: There is much evidence for the influence of low socio-economic status
      on poor health. It is, however, also important to study the ways in which people
      attain and retain their socio-economic status and the factors that predict
      changes in socio-economic status, such as a decrease in income. Such mobility
      also occurs in older populations, in which financial and health-related changes
      are very common, especially after retirement. METHODS: Three years of follow-up
      data from 1443 Dutch men and women aged 55 years and older who participated in
      the Study on Medical Information and Lifestyles Eindhoven (SMILE) were gathered.
      Logistic regression analyses were used to study the independent effects of
      physical and mental dysfunction and severity of chronic diseases and adverse
      personality factors on decrease in income. RESULTS: Social anxiety (OR = 1.62,
      95% CI: 1.09-2.40), physical dysfunction (OR = 1.71, 95% CI: 1.07-2.74) and
      severe diseases (OR = 1.37, 95% CI: 1.05-1.78) were significant predictors of
      decrease in income. These contributions were independent of each other, and
      remained robust after controlling for other confounding factors, such as gender,
      age and educational level and change in employment status. Mental dysfunction and
      other personality characteristics, such as hostility and mastery, did not
      contribute to decrease in income. CONCLUSION: Social anxiety and poor physical
      health are relevant factors associated with decrease in income in old age. The
      findings suggest that these factors are important in retaining one's socio
      economic status. Future longitudinal research is necessary to further disentangle
      the mechanisms and pathways related to socio-economic health inequalities along
      the life-course.

PMID- 19380334
TI  - Molecular dynamics studies on the interactions of PTP1B with inhibitors: from the
      first phosphate-binding site to the second one.
AB  - Protein tyrosine phosphatases 1B (PTP1B) is a major negative regulator of both
      insulin and leptin signaling pathways. In view of this, it becomes an important
      target for drug development against cancers, diabetes and obesity. The aim of the
      current study is to use the long time-scale molecular dynamics (MD) simulations
      to investigate the structural and dynamic factors that cause its inhibition by
      INTA and INTB, the two most potent and highly selective PTP1B inhibitors known so
      far. In order to investigate the mode of collective motions that is vitally
      important to the biological function, the covariance matrix of C(alpha) atoms was
      introduced for performing the dynamic analysis of the inhibition systems. It has
      been observed that the conformational and dynamic features of WPD-Loop, R-Loop
      and S-Loop play a key role in providing a smooth entrance for the inhibitors
      moving into the binding pocket as well as a favorable microenvironment to
      stabilize them. Furthermore, the hydrogen bonding networks formed around the
      active site with INTA and INTB may be the main reason of why the inhibition of
      PTP1B by the two ligands is so potent and selective. All these findings might
      provide useful insights for developing novel and effective drugs to treat cancer,
      diabetes and obesity.

PMID- 19380335
TI  - Aprotinin increases mortality as compared with tranexamic acid in cardiac
      surgery: a meta-analysis of randomized head-to-head trials.
AB  - To determine whether aprotinin increases mortality as compared with tranexamic
      acid in cardiac surgery, we performed a meta-analysis of randomized head-to-head
      trials. All prospective randomized head-to-head trials of aprotinin vs.
      tranexamic acid enrolling patients undergoing cardiac surgery were identified
      using a web-based search engine (PubMed). For each study, data regarding
      mortality in both the aprotinin and tranexamic acid groups were used to generate
      risk ratios (RRs) and 95% confidence intervals (CIs). Study-specific estimates
      were combined using inverse variance-weighted averages of logarithmic RRs in
      random-effects models. Our search identified nine trials (eight trials included
      in the previous meta-analysis and the blood conservation using antifibrinolytics
      in a randomized trial [BART] study). Seven trials were composed of low-risk
      patients (n=1291) and two trials consisted of low-risk patients (n=1628). Pooled
      analysis of the nine trials demonstrated a statistically significant 45% increase
      in mortality with aprotinin relative to tranexamic acid therapy (RR, 1.45; 95%
      CI, 1.00 [1.0002]-2.11; P=0.05 [0.0499]). The present meta-analysis of updated
      all randomized head-to-head trials, the best evidence, demonstrated a
      statistically significant increase in mortality with aprotinin relative to
      tranexamic acid therapy in cardiac surgery.

PMID- 19380336
TI  - Single high-dose intramyocardial administration of erythropoietin promotes early
      intracardiac proliferation, proves safety and restores cardiac performance after
      myocardial infarction in rats.
AB  - Various studies demonstrate erythropoietin (EPO) as a cardioprotective growth
      hormone. Recent findings reveal EPO in addition might induce proliferation
      cascades inside myocardium. We aimed to evaluate whether a single high-dose
      intramyocardial EPO administration safely elevates early intracardiac cell
      proliferation after myocardial infarction (MI). Following permanent MI in rats
      EPO (3000 U/kg) in MI EPO-treatment group (n=99) or saline in MI control group
      (n=95) was injected along the infarction border. Intramyocardial EPO injection
      activated the genes of cyclin D1 and cell division cycle 2 kinase (cdc2) at 24 h
      after MI (n=6, P<0.05) evaluated by real time-PCR. The number of Ki-67+
      intracardiac cells analyzed following immunohistochemistry was significantly
      enhanced by 45% in the peri-infarction zone at 48 h after EPO treatment (n=6,
      P<0.001). Capillary density was significantly enhanced by 17% as early as seven
      days (n=6, P<0.001). After six weeks, left ventricular performance assessed by
      conductance catheters was restored under baseline and dobutamine induced stress
      conditions (n=11-14, P<0.05). No thrombus formation was observed in the heart and
      in distant organs. No deleterious systemic adverse effects were apparent. Single
      high-dose intramyocardial EPO delivery proved safety and promoted early
      intracardiac cell proliferation, which might in part have contributed to an
      attenuated myocardial functional decline.

PMID- 19380337
TI  - A randomised controlled trial comparing Mediwrap heat retention and forced air
      warming for maintaining normothermia in thoracic surgery.
AB  - Hypothermia is one of the common complications in the perioperative period.
      Currently, normothermia is maintained with forced air warming (FAW) or passive
      heat retention methods. We compared the efficacy of the Mediwrap blanket with FAW
      in maintaining normothermia during intra-operative period in thoracic surgery in
      a prospective randomised controlled trial on 30 patients. Core temperature was
      measured at 30-min intervals in the perioperative period and the time taken to
      attain baseline in the postoperative periods in the two groups was compared.
      There was no difference in core temperatures between the groups during pre- and
      intra-operative period, with mean+/-S.D. final core temperatures of 36.2+/-0.6
      degrees C with Mediwrap and 36+/-0.9 degrees C with the FAW blanket. However, the
      postoperative core temperatures were significantly higher in the Mediwrap group.
      The time required to reach baseline temperature was lower in the Mediwrap group
      with a mean+/-S.D. of 66+/-66 min as compared to 161+/-108 min in the FAW group.
      The Mediwrap blanket is as effective as the FAW blanket in maintaining core body
      temperature during thoracotomy when applied thirty minutes before the surgery.

PMID- 19380338
TI  - Sudden hemothorax following lobectomy caused by staple.
AB  - A 74-year-old female with lung cancer underwent a right lower lobectomy by video
      assisted thoracic surgery (VATS), and suddenly developed hemothorax soon after
      discharge. The bleeding point was an intercostal artery which faced a stump of
      the right lower vein divided by a stapler. Operative finding suggested that it
      was caused by an incidental injury of the artery by a staple.

PMID- 19380339
TI  - eComment: Individualization of blood cardioplegia administration mode.

PMID- 19380340
TI  - eComment: Re: Is repeated administration of blood-cardioplegia really necessary?

PMID- 19380343
TI  - eComment: CorBeat trileaflet mechanical full-flow heart valve prosthesis versus
      native human aortic valves - evaluation of functional performance.

PMID- 19380344
TI  - eComment: Vacuum-assisted closure in thoracic surgery - an alternative to
      pedicled latissimus dorsi flap?

PMID- 19380345
TI  - eComment: Spontaneous coronary artery dissection: a fatal cause of myocardial
      infarction in pregnancy.

PMID- 19380346
TI  - eComment: Under representation of Germany's specialized thoracic surgery units in
      maximum service hospitals impacts treatment.

PMID- 19380347
TI  - eComment: Aortic root replacement using the reimplantation technique: tips and
      tricks.

PMID- 19380348
TI  - Prediction of fatal or near fatal arrhythmias in patients with a depressed left
      ventricular function after an acute myocardial infarction.

PMID- 19380349
TI  - Non-conventional markers of atherosclerosis before and after gastric banding
      surgery.
AB  - AIMS: Obesity and type 2 diabetes are associated with increased cardiovascular
      risk and elevation of traditional and non-traditional risk markers. As bariatric
      surgery reduces overweight and improves metabolic derangement, we examined a
      cluster of established and emerging cardiovascular risk factors, such as soluble
      CD40 ligand (sCD40L) and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)),
      which might improve prediction of future cardiovascular events because of their
      more direct involvement in plaque destabilization. METHODS AND RESULTS: Obese
      patients [n = 32, body mass index (BMI) 46.1 +/- 5.9 kg/m(2)] underwent clinical
      examinations and blood sampling for measurement of glucose and lipid parameters
      as well as non-traditional cardiovascular risk markers, i.e. high-sensitivity C
      reactive protein, plasminogen activator inhibitor-1 (PAI-1), soluble cellular
      adhesion molecules (CAM), MMP-2, MMP-9, CD40L, and Lp-PLA(2) before and after 1
      year following laparoscopic adjustable gastric banding (LAGB), respectively. In
      patients undergoing LAGB, blood pressure (P < 0.0001) and blood glucose (P =
      0.02) were significantly lowered by approximately 16% as well as triglyceride
      levels by approximately 29% (P = 0.002). In addition to a decrease of the
      inflammatory and pro-thrombotic marker PAI-1 (P = 0.001), CAMs, and MMP-9 (P =
      0.004) were reduced, whereas no change was observed for plasma levels of MMP-2,
      sCD40L, and Lp-PLA(2) after LAGB, respectively. Individual changes in (ICAM-1)
      intercellular adhesion molecule-1 (DeltaICAM-1) were related to changes in
      insulin (Deltafasting insulin) before and after LAGB (r = 0.36 and r = 0.38; both
      P = 0.04). E-selectin correlated positively with changes in BMI (r = 0.38; P =
      0.04 and r = 0.36; P = 0.05), while Lp-PLA(2) concentration was negatively
      correlated with BMI (r =-0.41; P = 0.02) after 1 year. Changes were comparable in
      both overweight diabetic and non-diabetic subjects. CONCLUSION: LAGB not only
      induced weight loss but also an improvement in the subclinical pro-inflammatory
      state. However, concentrations of most of the non-traditional risk factors for
      plaque instability, i.e. MMP-9, sCD40L, and Lp-PLA(2) remained unchanged.

PMID- 19380350
TI  - Light-dependent intracellular positioning of mitochondria in Arabidopsis thaliana
      mesophyll cells.
AB  - Mitochondria, the power house of the cell, are one of the most dynamic cell
      organelles. Although there are several reports on actin- or microtubule-dependent
      movement of mitochondria in plant cells, intracellular positioning and motility
      of mitochondria under different light conditions remain open questions.
      Mitochondria were visualized in living Arabidopsis thaliana leaf cells using
      green fluorescent protein fused to a mitochondrion-targeting signal. In darkness,
      mitochondria were distributed randomly in palisade cells. In contrast,
      mitochondria accumulated along the periclinal walls, similar to the accumulation
      response of chloroplasts, when treated with weak blue light (470 nm, 4 micromol
      m(-2) s(-1)). Under strong blue light (100 micromol m(-2) s(-1)), mitochondria
      occupied the anticlinal positions similar to the avoidance response of
      chloroplasts and nuclei. While strong red light (660 nm, 100 micromol m(-2) s(
      1)) induced the accumulation of mitochondria along the inner periclinal walls,
      green light exhibited little effect on the distribution of mitochondria. In
      addition, the mode of movement of individual mitochondria along the outer
      periclinal walls under different light conditions was precisely analyzed by time
      lapse fluorescence microscopy. A gradual increase in the number of static
      mitochondria located in the vicinity of chloroplasts with a time period of blue
      light illumination clearly demonstrated the accumulation response of
      mitochondria. Light-induced co-localization of mitochondria with chloroplasts
      strongly suggested their mutual metabolic interactions. This is the first
      characterization of the light-dependent redistribution of mitochondria in plant
      cells.

PMID- 19380351
TI  - Chlorella starch branching enzyme II (BEII) can complement the function of BEIIb
      in rice endosperm.
AB  - In monocots, starch branching enzyme II (BEII) was functionally differentiated
      into BEIIa and BEIIb after separation from the dicots, and in cereals BEIIb plays
      a distinct role in amylopectin biosynthesis in the endosperm. The present study
      was conducted to examine to what extent a green algal BEII has an overlapping
      function with BEIIb in starch biosynthesis by introducing the Chlorella BEII gene
      into an amylose-extender (ae) mutant of rice. Chlorella BEII was found to
      complement the contribution of the rice endosperm BEIIb to the structures of
      amylopectin and starch granules because these mutated phenotypes were recovered
      almost completely to those of the wild type by the expression of Chlorella BEII.
      When the recombinant BE enzymes were incubated with the rice ae amylopectin, the
      branching pattern of Chlorella BEII was much more similar to that of rice BEIIb
      rather than rice BEIIa. Detailed analyses of BE reaction products suggests that
      BEIIb and Chlorella BEII only transfer chains with a degree of polymerization
      (DP) of 6 and 7, whereas BEIIa preferably transfers short chains with a DP of
      about 6-11. These results show that the Chlorella BEII is functionally similar to
      rice BEIIb rather than BEIIa.

PMID- 19380352
TI  - Temperament and character profiles of sasang typology in an adult clinical
      sample.
AB  - The purpose of this study was to examine the biopsychological personality
      profiles of traditional Korean Sasang typology based on the Temperament and
      Character Inventory (TCI) in a Korean adult clinical sample. A total of 97 adults
      completed the Korean version of the TCI. The participants were classified as one
      of three traditional Korean Sasang types (31 So-Yang, 41 Tae-Eum, 25 So-Eum) by
      three specialists in Sasang typology. The seven dimensions of TCI were compared
      between the different Sasang types using analysis of variance (ANOVA) and profile
      analysis. There were no significant differences in age, gender and education
      across the Sasang types. The TCI profile for each of the Sasang types was
      significantly different (profile analysis, df = 5.038, F = 3.546, P = .004).
      There were significant differences in the temperament dimensions of Novelty
      Seeking (F = 3.43, P = .036) and Harm Avoidance (F = 5.43, P = .006) among the
      Sasang types. The Novelty Seeking score of the So-Yang type (31.90 +/- 9.87) was
      higher than that of the So-Eum type (25.24 +/- 9.21; P = .019) while the So-Eum
      type (44.64 +/- 8.47) scored higher on the Harm Avoidance score compared to the
      So-Yang type (35.16 +/- 11.50; P = .003). There were no significant differences
      in the temperament dimension of Reward Dependence and Persistence, and the three
      character dimensions of Self-Directedness, Cooperativeness and Self
      Transcendence. Results demonstrated distinct temperament traits associated with
      traditional Korean Sasang types using an objective biopsychological personality
      inventory. With further study, the Sasang typology may lead to enhanced clinical
      safety and efficacy as part of personalized medicine with traditional medicine.

PMID- 19380353
TI  - Tradition, teamwork, and tailored treatment: surgical oncology in the genomic
      era.

PMID- 19380354
TI  - Clinical predictors of quality of life in patients with initial differentiated
      thyroid cancers.
AB  - BACKGROUND: Patients with differentiated thyroid cancer (DTC) usually have a good
      prognosis. Traditionally, treatment success in patients with cancer has been
      evaluated by survival time. Recently, it has been observed that the diagnosis and
      treatment of cancer also have a strong effect on the quality of life (QOL) of
      these patients. OBJECTIVE: To assess the QOL of patients with DTC and its
      potential clinical predictors. DESIGN: Cross-sectional analysis. SETTING: A
      tertiary cancer institution. PATIENTS: One hundred fifty-four patients submitted
      to thyroidectomy (1997-2006) were evaluated using the University of Washington
      Quality of Life questionnaire. MAIN OUTCOME MEASURES: Descriptive analysis of the
      results was done, as bivariate and multivariate analyses to compare each
      independent variable with each of 13 QOL domains. RESULTS: Patients 45 years or
      younger had better recreation scores than did patients older than 45 years (P =
      .04). Thirty-eight patients were submitted to neck dissection. Patients submitted
      to modified radical neck dissection reported worse chewing and shoulder scores
      than did patients submitted to selective paratracheal lymph node dissection only
      and those without neck dissection (P = .003 and P = .004, respectively). Patients
      who received more than 150 mCi of radioactive iodine therapy (RIT) reported
      significantly worse pain, swallowing, chewing, speech, taste, anxiety, and
      composite scores. Comorbidities showed significant effect on recreation,
      activity, speech, saliva, and composite scores (P = .02, P = .046, P = .02, P =
      .01, and P = .008, respectively). In multivariate analysis, RIT is the only
      variable associated with a worse composite score (P = .003). CONCLUSION: Although
      QOL after treatment of thyroid cancer can be considered good for most patients,
      those submitted to RIT at doses higher than 150 mCi are at risk for poor QOL and,
      therefore, may need more intensive follow-up and treatment.

PMID- 19380355
TI  - Inhibition of the growth of papillary thyroid carcinoma cells by CI-1040.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC), the most common type of thyroid
      malignancy, usually possesses mutations, either RET/PTC rearrangement or BRAF
      mutation. Both mutations can activate the mitogen-activated protein kinase
      kinase/extracellular signal-related kinase signaling transduction pathway, which
      results in activation of transcription factors that regulate cellular
      proliferation, differentiation, and apoptosis. OBJECTIVE: To test the effects of
      CI-1040 (PD184352), a specific MEK1/2 inhibitor, on PTC cells carrying either an
      RET/PTC1 rearrangement or a BRAF mutation. DESIGN: The effects of CI-1040 on PTC
      cells were evaluated in vitro and in vivo. MAIN OUTCOME MEASURES: The effects of
      CI-1040 on PTC cells were evaluated in vitro using a cell proliferation assay,
      cell cycle analysis, and immunoblotting. The antitumor effects of CI-1040 in vivo
      were evaluated in an orthotopic mouse model. RESULTS: The concentrations of CI
      1040 needed to inhibit 50% cell growth were 0.052microM for PTC cells with a BRAF
      mutation and 1.1microM for PTC cells with the RET/PTC1 rearrangement. After 3
      weeks of oral administration of CI-1040 (300 mg/kg/d) to mice with orthotopic
      tumor implants of PTC cells, the mean tumor volume of implants bearing the
      RET/PTC1 rearrangement (n = 5) was reduced 47.5% compared with untreated mice
      (from 701.9 to 368.5 mm(3)), and the mean volume of implants with a BRAF mutation
      (n = 8) was reduced 31.3% (from 297.3 to 204.2 mm(3)). CONCLUSIONS: CI-1040
      inhibits PTC cell growth in vitro and in vivo. Because RET/PTC rearrangements are
      unique to thyroid carcinomas and a high percentage of PTCs possess either
      mutation, these findings support the clinical evaluation of CI-1040 for patients
      with PTC.

PMID- 19380356
TI  - Influence of previous radiation exposure on pathologic features and clinical
      outcome in patients with thyroid cancer.
AB  - OBJECTIVE: To determine whether previous radiation exposure to the head and neck
      is related to less favorable pathologic and clinical outcome in patients after
      surgical management of thyroid cancer. DESIGN: Retrospective chart review.
      SETTING: Academic teaching hospital (referral center). PATIENTS: All patients
      with diagnosed thyroid cancer who had been exposed to radiation before surgical
      treatment were retrospectively identified from the thyroid cancer database at our
      institution (1963-2007). One hundred twenty-five patients (95 women and 30 men)
      were included. Inclusion criteria included surgical treatment for thyroid cancer
      and a history of exposure to radiation at least 3 years before diagnosis of the
      disease. MAIN OUTCOME MEASURES: Pathologic features and data related to disease
      recurrence, distant metastasis, and survival. RESULTS: Mean (range) age at first
      exposure to radiation was 19.4 (1-65) years, and mean lag time to diagnosis of
      disease was 28.7 (3-60) years. Patients were treated surgically with either total
      or near-total thyroidectomy (83%) or partial or subtotal thyroidectomy (17%).
      Pathologic diagnoses included 111 papillary carcinomas (89%). Sixty-three percent
      of patients had multifocal disease, 12% had lymphovascular tumor invasion, and
      26% had direct extrathyroid extension of disease. Twenty-five percent of patients
      had metastases to cervical lymph nodes, and 9% had distant metastases. Sixteen
      percent of patients experienced local recurrence of disease. At last follow-up,
      86% of patients were alive and free of disease, 8% were alive with disease, 4%
      had died of thyroid cancer, and 2% had died of an unrelated cause. Compared with
      other patients with thyroid cancer, this radiation-exposed cohort was more likely
      to undergo total thyroidectomy, multiple operative procedures, and external
      radiotherapy. A higher percentage had multifocal disease, extrathyroid extension,
      stage IV disease, and distant metastases. At follow-up, fewer patients were free
      of disease, and more patients had died of thyroid disease. CONCLUSION: Patients
      who have been exposed to radiation have more aggressive disease and worse
      clinical outcome than other patients with thyroid cancer.

PMID- 19380357
TI  - Identification of the external branch of the superior laryngeal nerve during
      thyroidectomy.
AB  - OBJECTIVES: To determine the feasibility of identification of the external branch
      of the superior laryngeal nerve (EBSLN) during routine thyroidectomy and to
      describe the EBSLN position according to the Cernea classification system.
      DESIGN: Prospective case series. SETTING: Academic tertiary care center.
      PATIENTS: One hundred twelve consecutive patients undergoing hemithyroidectomy or
      total thyroidectomy by the senior author between August 15 and December 31, 2007.
      INTERVENTIONS: None. MAIN OUTCOME MEASURE: Proportion of EBSLNs identified.
      Secondary outcome measures included EBSLN position according to Cernea
      classification and correlation with patient and gland characteristics. RESULTS:
      Three of 178 EBSLNs (1.7%) could not be identified using the routine technique.
      The EBSLN was found in the highest-risk position (Cernea type 2b, crossing the
      superior vascular pedicle below the upper border of the gland) in 48.3% of cases,
      and in the lowest-risk position (Cernea type 1, crossing more than 1 cm above the
      upper border) in 7.3%. Specimens larger in weight and in dimension were
      correlated with type 2b nerves. CONCLUSIONS: The EBSLN can be routinely
      identified during thyroidectomy. Moreover, many EBSLNs are in position to be at
      high risk of injury during ligation of the superior vascular pedicle.

PMID- 19380358
TI  - Voice-related quality of life after treatment of laryngeal cancer.
AB  - OBJECTIVE: To determine patient-perceived voice-related quality of life in
      patients treated with various methods based on the results of Voice-Related
      Quality of Life (VRQOL) and Voice Handicap Index-10 (VHI-10) questionnaires.
      DESIGN: The VRQOL and VHI-10 questionnaires. SETTING: University hospital.
      PATIENTS: One hundred thirty-seven patients who had received definitive treatment
      of laryngeal cancer were followed-up at Hokkaido University Hospital, Sapporo,
      Japan, and were alive with no evidence of malignancy at the time of the survey.
      MAIN OUTCOME MEASURE: Patient-perceived voice-related quality of life based on
      the results of the VRQOL and VHI-10 questionnaires. RESULTS: The mean VRQOL
      scores for patients who had undergone radiotherapy (n = 63), chemoradiotherapy (n
      = 29), laser surgery (n = 14), or total laryngectomy (n = 27) as final treatment
      of laryngeal cancer were 92.6, 92.9, 85.5, and 68.4, respectively; the mean VHI
      10 scores were 2.87, 2.34, 5.43, and 11.26, respectively. CONCLUSION: The VRQOL
      and VHI-10 questionnaires are important in judging the overall effectiveness of
      treatment options for laryngeal cancer.

PMID- 19380359
TI  - Screening for dysfunction to promote multidisciplinary intervention by using the
      University of Washington Quality of Life Questionnaire.
AB  - OBJECTIVE: To investigate the potential of the University of Washington Quality
      of Life Questionnaire (UW-QOL) in routine clinics as a quick screening tool for
      possible dysfunction in patients after treatment of head and neck cancer. DESIGN:
      Retrospective analysis. SETTING: Regional Maxillofacial Unit, Aintree University
      Hospitals National Health Service Foundation Trust Liverpool, a National Health
      Service teaching hospital. PATIENTS: Consecutive disease-free patients with oral
      or oropharyngeal squamous cell carcinoma, who had undergone primary surgery with
      or without adjuvant radiotherapy, for whom UW-QOL version 4 data from 2000 to May
      2006 were available in our research database; and consecutive patients from
      previous studies (4 postal surveys of disease-free patients with oral or
      oropharyngeal squamous cell carcinoma, 1 clinic-based study that targeted speech
      and swallowing in patients with oropharyngeal disease, 1 that evaluated shoulder
      function in patients with various diagnoses, and 1 that recruited patients
      without cancer attending a general dental practice). MAIN OUTCOME MEASURES:
      Cutoff strategies for further evaluation/intervention derived from studies using
      the UW-QOL in parallel with 13 other established questionnaires. Effects of
      preferred cutoffs on trigger variation were assessed with the use of all
      available UW-QOL version 4 data (615 patients). RESULTS: Trigger rates for
      further intervention fell between 9% (recreation and speech) and 16%
      (swallowing). Eighty-one percent of patients with free-flap surgery and adjuvant
      therapy for T3 or T4 tumors met the trigger criteria at around 2 years, with 42%
      meeting the trigger on 3 or more domains. CONCLUSION: The fourth version of the
      UW-QOL is suitable for routine screening in clinical practice.

PMID- 19380360
TI  - Acceptance of major surgical procedures and quality of life among long-term
      survivors of advanced head and neck cancer.
AB  - OBJECTIVE: To evaluate the acceptance of major surgical procedures and quality of
      life among long-term survivors of advanced head and neck cancer treated at a
      single institution. DESIGN: Cross-sectional analysis of a consecutive series of
      patients. SETTING: Tertiary care cancer center. PATIENTS: Participants had
      advanced (T3 and T4) head and neck cancer, had undergone a surgical procedure
      with or without postoperative radiotherapy, and had a minimum disease-free
      survival duration of 1 year. Eligible participants completed a questionnaire
      about their attitudes toward long-term outcomes and the University of Washington
      Quality of Life Questionnaire (UW-QOL). MAIN OUTCOME MEASURE: Descriptive
      analyses of the results and comparisons of the scores for each UW-QOL domain.
      RESULTS: A total of 273 patients were included in the study. Most were men
      (74.4%), with a median age of 56 years. The tumor site was the oral cavity in 101
      patients (37.0%), larynx in 91 (33.3%), oropharynx in 64 (23.4%), and hypopharynx
      in 17 (6.2%). There were 167 patients (61.2%) with T3 tumors and 106 (38.8%) with
      T4 tumors. Adjuvant radiotherapy was performed in 153 patients (56.0%). Global
      quality of life was considered good to excellent by 162 patients (59.3%), and the
      mean UW-QOL composite score was 79.3. Most patients (91.2%) reported that they
      would undergo the same treatment if they had it to do again, and 95.6% reported
      that they would not like to exchange their present outcome for another treatment
      option with a lower chance of cure but with a possibly improved quality of life.
      CONCLUSION: In this series, the vast majority of patients considered a radical
      surgical procedure an acceptable treatment and reported a good quality of life.

PMID- 19380361
TI  - Influences and predictors of long-term quality of life in head and neck cancer
      survivors.
AB  - OBJECTIVE: To examine the impact of clinical predictors (pretreatment variables)
      and other influences (treatment and posttreatment variables) on long-term quality
      of life (QOL) in patients treated for squamous cell carcinoma of the upper
      aerodigestive tract. We hypothesized that baseline QOL and comorbidity would be
      predictors of QOL 1 year after treatment. DESIGN: Retrospective cohort study.
      SETTING: Academic Medical Center in Seattle, Washington. PATIENTS: Patients (N =
      173) with baseline (pretreatment) and 1-year posttreatment QOL data. MAIN OUTCOME
      MEASURE: Head and neck-specific QOL scores at 1 year after treatment (as measured
      by the University of Washington Quality of Life [UW-QOL] scale). RESULTS: We
      identified strong relationships between 1-year UW-QOL scores and baseline UW-QOL
      scores (correlation coefficient [Pearson r] = 0.58; P < .001) and pretreatment
      comorbidity (as measured by the Adult Comorbidity Evaluation scale) (Spearman rho
      = 0.23; P < .001). T stage and N stage were also predictive. Although not a
      predictive variable, the presence of a gastrostomy tube at 1 year also strongly
      influenced 1-year UW-QOL scores. Patients with gastrostomy tubes had UW-QOL
      scores 11.5 points worse than those without (P < .001), when a 7-point difference
      is considered clinically significant. In predictive multivariate regression
      models, pretreatment QOL scores, comorbidity, and T stage had the strongest
      prognostic impact on 1-year UW-QOL scores. CONCLUSIONS: In bivariate analyses,
      the presence of a gastrostomy tube worsens UW-QOL scores at 1 year and requires
      further investigation. When considering predictive variables only, baseline QOL
      and comorbidity appear to have strong influences on posttreatment QOL and have
      greater impact than treatment modality. Greater attention to these baseline
      predictors should be given when counseling patients about long-term function
      after treatment.

PMID- 19380362
TI  - Laser surgery for early glottic cancer: impact of margin status on local control
      and organ preservation.
AB  - OBJECTIVE: To assess the impact of margin status on disease-free survival,
      overall survival, and organ preservation in early glottic cancer treated by
      endoscopic laser surgery. DESIGN: Prospective nonrandomized study. SETTING:
      Tertiary referral center. PATIENTS: A total of 274 patients with untreated
      (possibly biopsied) cTis, cT1a/b, cT2, cN0 glottic cancer; adequate exposure of
      the glottic region; no contraindications to general anesthesia; and the ability
      to give informed consent. INTERVENTIONS: European Laryngological Society laser
      cordectomy. Patients with negative margins (>1 mm) were followed, patients with
      close margins (< or =1 mm) or 1 positive margin (tumor on margin) had another
      operation, and patients with more than 1 positive margin had postoperative
      radiotherapy. Median follow-up was 58 months. MAIN OUTCOME MEASURES: Eight-year
      disease-free survival, 5-year overall survival, and organ preservation rate.
      RESULTS: Margins were negative in 180 patients, close in 40, and positive in 54.
      A second laser resection was performed in 36 of 94 patients with close or
      positive margins. Radiotherapy was administered to 36 patients. Patients with
      close or positive margins who did not undergo further treatment had a greater
      recurrence risk (hazard ratio, 2.53; 95% confidence interval, 0.97-6.59, P = .06)
      than did those with negative margins, mainly owing to relapses in 5 of the 8
      protocol breakers with positive margins not treated further. Eight-year relapse
      free survival was 88.2%, 5-year overall survival was 90.9%, and the larynx was
      preserved in 97.1%. CONCLUSIONS: Laser removal of early glottic cancer is
      oncologically adequate with margins greater than 1 mm from the tumor edge.
      Positive margins require further treatment; close margins may require further
      treatment depending on tumor characteristics.

PMID- 19380363
TI  - Chronic periodontitis-human papillomavirus synergy in base of tongue cancers.
AB  - OBJECTIVE: To assess whether chronic periodontitis history predicts human
      papillomavirus (HPV) status in patients with base of tongue cancers. DESIGN: Case
      control study using existing patient data. SETTING: Roswell Park Cancer
      Institute. PATIENTS: Thirty patients newly diagnosed with base of tongue squamous
      cell carcinoma between 1999 and 2005 for whom both tumor samples and periodontal
      records were available. Patients younger than 21 years, edentulous,
      immunocompromised, and those with a history of cancer were excluded.
      Periodontitis history was assessed on the basis of alveolar bone loss (in
      millimeters) from panoramic radiographs by one examiner who was blinded to cancer
      status. MAIN OUTCOME MEASURE: HPV-16 and HPV-18 DNA were identified on paraffin
      embedded tumor samples by polymerase chain reaction. Multiple logistic regression
      was used to estimate odds ratios and 95% confidence intervals. RESULTS: The
      prevalence of tumors positive for HPV-16 DNA was 21 of 30 (70%). None of the
      samples were positive for HPV-18 DNA. Compared with participants with HPV
      negative tumors, patients with HPV-positive tumors had significantly higher mean
      alveolar bone loss (3.90 mm vs 2.85 mm, P = .01). After adjustment for age at
      diagnosis, sex, race/ethnicity, alcohol use, smoking status, and number of
      missing teeth, every millimeter of alveolar bone loss was associated with an
      approximately 4-fold (odds ratio, 3.96; 95% confidence interval, 1.18-13.36)
      increased risk of HPV-positive tumor status. Number of missing teeth was not
      associated with tumor HPV status (odds ratio, 0.95; 95% confidence interval, 0.74
      1.21). CONCLUSIONS: Chronic periodontitis may be a significant factor in the
      natural history of HPV infection in patients with base of tongue cancers.
      Additional confirmation in larger studies is required.

PMID- 19380365
TI  - Bidirectional association of anogenital and oral cavity/pharyngeal carcinomas in
      men.
AB  - OBJECTIVE: To test the hypothesis of a bidirectional association of anogenital
      and oral cavity/pharyngeal human papillomavirus (HPV)-associated cancers in men.
      DESIGN: Population-based epidemiological study using the Surveillance,
      Epidemiology, and End Results cancer database. SETTING: Population-based cancer
      study involving patients receiving care in the United States. PARTICIPANTS: The
      study included 47,308 men 20 years and older with an index oral cavity/pharyngeal
      or anogenital cancer. MAIN OUTCOME MEASURE: Second primary HPV-associated cancers
      (anogenital or oral cavity/pharyngeal) or HPV-unrelated cancers (prostate,
      bladder, or colon). RESULTS: The standardized incidence ratio (SIR) was elevated
      for both anogenital cancer following oral cavity/pharyngeal cancer (SIR, 1.9; 95%
      confidence interval [CI], 1.2-2.7) and oral cavity/pharyngeal cancer following
      anogenital cancer (SIR, 3.0; 95% CI, 2.1-4.2). The increase in SIR was most
      pronounced for tonsillar cancer following anal cancer (SIR, 8.4; 95% CI, 2.7
      19.6). The risk of second primary HPV-associated cancers did not vary
      significantly by age, race, year of diagnosis, or geographic location but was
      greater among never-married men, particularly for anal cancer following oral
      cavity/pharyngeal cancer (SIR, 6.5; 95% CI,1.8-16.7 in never-married men, but
      SIR, 1.6; 95% CI, 0.7-3.1 in ever-married men) and for tonsillar cancer following
      anogenital cancer (SIR, 13.0; 95% CI, 3.5-33.2 in never-married men, but SIR,
      3.8; 95% CI, 1.0-9.7 in ever-married men). Other than a slightly increased risk
      of tongue cancer following colon cancer (SIR, 1.3; 95% CI, 1.1-1.6), there was no
      increased risk of oral cavity/pharyngeal or anogenital cancer following HPV
      unrelated cancers or vice versa. CONCLUSION: The association between index and
      second primary anogenital and oral cavity/pharyngeal cancers, strongest in never
      married men, supports the influence of sexual behavior on the risk of HPV
      associated head and neck cancers.

PMID- 19380364
TI  - Robot-assisted surgery for upper aerodigestive tract neoplasms.
AB  - OBJECTIVES: To assess the feasibility and safety of performing robot-assisted
      resections of head and neck tumors, and to predict which variables lead to
      successful robot-assisted resection and better functional outcome. DESIGN:
      Prospective nonrandomized clinical trial. SETTING: Academic tertiary referral
      center. PATIENTS: Thirty-six patients with oral cavity, oropharyngeal,
      hypopharyngeal, or laryngeal tumors. INTERVENTION: Robot-assisted resection of
      indicated tumors. MAIN OUTCOME MEASURES: Ability to perform robot-assisted
      resection, final pathologic margin status, ability to extubate postoperatively,
      need for tracheotomy tube, and need for gastrostomy tube. Any clinically
      significant complications were recorded. RESULTS: Thirty-six patients
      participated in the study. Eight patients had previously been treated for head
      and neck cancer. Twenty-nine patients (81%) underwent successful robotic
      resection. Negative margins were obtained in all 29 patients. Twenty-one of 29
      patients were safely extubated prior to leaving the operating room. One patient
      required short-term tracheotomy tube placement. A total of 9 patients were
      gastrostomy tube dependent (2 preoperatively, 7 postoperatively). Factors
      associated with successful robotic resection were lower T classification (P =
      .01) and edentulism (P = .07). Factors associated with gastrostomy tube
      dependence were advanced age (P = .02), tumor location in the larynx (P < .001),
      higher T classification (P = .02), and lower preoperative M. D. Anderson
      Dysphagia Inventory score (P = .04). CONCLUSIONS: Robot-assisted surgery is
      feasible and safe for the resection of select head and neck tumors. This clinical
      series demonstrates that robotic surgery can be utilized successfully in patients
      with T1 to T4 lesions located in the oral cavity, oropharynx, hypopharynx, and
      larynx with good preservation of swallow function.

PMID- 19380366
TI  - Double free-flap reconstruction: indications, challenges, and prospective
      functional outcomes.
AB  - OBJECTIVE: To investigate the increasing use of double free flaps in the
      reconstruction of large head and neck defects. DESIGN: A 5-year retrospective
      medical record review in a large tertiary care head and neck oncology program.
      Prospectively collected functional data were also analyzed. SETTING: Academic
      research. PATIENTS: A consecutive series of 35 patients (24 men and 11 women;
      mean age, 57.7 years). MAIN OUTCOME MEASURES: The use of double free flaps in the
      reconstruction of large head and neck defects and prospective functional
      outcomes. RESULTS: The most common indication for surgery (n = 25 [71.4%]) was
      squamous cell carcinoma. The most common double free-flap combination (n = 22
      [62.9%]) included an osteocutaneous fibular free flap with a fasciocutaneous
      radial forearm free flap. Objective evaluation by naive listeners demonstrated a
      mean single-word intelligibility score of 66.2% and a mean sentence
      intelligibility score of 84.8% in this group of patients. Modified barium swallow
      study results revealed no evidence of laryngeal penetration for swallowing liquid
      consistencies in 21 patients (60.0%), pudding consistencies in 30 patients
      (85.7%), and cookie consistencies in 32 patients (91.4%). CONCLUSIONS: With
      proper patient selection and planning and the use of 2 surgical teams, the length
      of surgery and complication rates are not significantly increased in double free
      flap reconstruction. Furthermore, by using 2 free flaps, the best osseous and
      soft-tissue elements may be independently selected, yielding appropriate tissue
      characteristics for ideal defect reconstruction.

PMID- 19380367
TI  - The effect of combination anti-endothelial growth factor receptor and anti
      vascular endothelial growth factor receptor 2 targeted therapy on lymph node
      metastasis: a study in an orthotopic nude mouse model of squamous cell carcinoma
      of the oral tongue.
AB  - OBJECTIVE: To evaluate the therapeutic effect of treatment with a combination of
      the monoclonal antibodies to the vascular endothelial growth factor receptor
      (DC101) and the epidermal growth factor receptor (cetuximab) in an orthotopic
      nude mouse model of metastatic squamous cell carcinoma of the oral tongue
      (SCCOT). DESIGN: In vivo study. SETTING: A translational research laboratory at a
      comprehensive cancer center. SUBJECTS: Male athymic nude mice aged 8 to 12 weeks.
      INTERVENTION: To develop orthotopic nude mouse models of SCCOT, OSC-19 cells or
      luciferase (Luc)-expressing OSC-19-Luc and JMAR-Luc cells were injected into the
      tongues of nude mice. Animals were randomly divided into 4 groups: DC101 alone,
      cetuximab alone, DC101 plus cetuximab, or placebo, and all treatments were
      administered twice per week for 4 weeks. The in vivo antitumor activity was
      monitored noninvasively by bioluminescence imaging. Tumors were resected at
      necropsy, and immunohistochemical and immunofluorescent staining were performed.
      MAIN OUTCOME MEASURES: Tumor size, bioluminescence, animal survival, and
      percentage of animals with lymph node metastasis. RESULTS: At the conclusion of
      the treatment period, the mean tumor volumes in the cetuximab alone and the DC101
      plus cetuximab groups had decreased significantly compared with those that
      received the placebo control (68% [P = .002] and 84% [P < .001], respectively).
      Significant effects of the treatment were also observed in bioluminescence
      imaging. Mice treated with DC101 plus cetuximab also lived longer and had a lower
      incidence of neck lymph node metastases compared with the control group (P =
      .003). CONCLUSIONS: Treatment with DC101 plus cetuximab inhibited the growth of
      SCCOT and decreased the incidence of the neck lymph node metastases in vivo.
      These results suggest that this combination treatment may be an effective
      strategy against metastatic SCCOT and warrants further preclinical trials.

PMID- 19380368
TI  - Commentary: Metabolic syndrome as a result of shift work exposure?

PMID- 19380369
TI  - Light-at-night, circadian disruption and breast cancer: assessment of existing
      evidence.
AB  - BACKGROUND: Breast cancer incidence is increasing globally for largely unknown
      reasons. The possibility that a portion of the breast cancer burden might be
      explained by the introduction and increasing use of electricity to light the
      night was suggested >20 years ago. METHODS: The theory is based on nocturnal
      light-induced disruption of circadian rhythms, notably reduction of melatonin
      synthesis. It has formed the basis for a series of predictions including that non
      day shift work would increase risk, blind women would be at lower risk, long
      sleep duration would lower risk and community nighttime light level would co
      distribute with breast cancer incidence on the population level. RESULTS:
      Accumulation of epidemiological evidence has accelerated in recent years,
      reflected in an International Agency for Research on Cancer (IARC) classification
      of shift work as a probable human carcinogen (2A). There is also a strong rodent
      model in support of the light-at-night (LAN) idea. CONCLUSION: If a consensus
      eventually emerges that LAN does increase risk, then the mechanisms for the
      effect are important to elucidate for intervention and mitigation. The basic
      understanding of phototransduction for the circadian system, and of the molecular
      genetics of circadian rhythm generation are both advancing rapidly, and will
      provide for the development of lighting technologies at home and at work that
      minimize circadian disruption, while maintaining visual efficiency and
      aesthetics. In the interim, there are strategies now available to reduce the
      potential for circadian disruption, which include extending the daily dark
      period, appreciate nocturnal awakening in the dark, using dim red light for
      nighttime necessities, and unless recommended by a physician, not taking
      melatonin tablets.

PMID- 19380371
TI  - Cohort Profile: The Metabolic syndrome and Cancer project (Me-Can).

PMID- 19380370
TI  - Dietary patterns and the risk of mortality: impact of cardiorespiratory fitness.
AB  - BACKGROUND: While dietary patterns that are both predictive of chronic disease
      and mortality have been identified, the confounding effects of cardiorespiratory
      fitness have not been properly addressed. The primary objective was to assess the
      relation between dietary patterns with all-cause mortality, while controlling for
      the potentially confounding effects of fitness. METHODS: This was a prospective
      cohort study. Participants consisted of 13 621 men and women from the Aerobics
      Center Longitudinal Study (ACLS). Participants completed a clinical exam and 3
      day diet record between 1987 and 1999. Participants were followed for mortality
      until 2003. Reduced rank regression (RRR) was used to identify dietary patterns
      that predicted unfavourable total and high-density lipoprotein-cholesterol,
      triglyceride, glucose, blood pressure, uric acid, white blood cell and body mass
      index values. RESULTS: One primary dietary pattern emerged and was labelled the
      Unhealthy Eating Index. This pattern was characterized by elevated consumption of
      processed and red meat, white potato products, non-whole grains, added fat and
      reduced consumption of non-citrus fruits. The hazard ratio for all-cause
      mortality in the fifth vs the first quintile of the Unhealthy Eating Index was
      1.40 (1.02-1.91). This risk estimate was reduced by 13.5 and 55.0% after
      controlling for self-reported physical activity and fitness, respectively.
      CONCLUSION: In this study the association between diet and overall mortality was,
      in large part, confounded by fitness.

PMID- 19380372
TI  - Oxidative stress and antioxidant status in neonates born to pre-eclamptic mother.
AB  - OBJECTIVE: Pre-eclampsia is a significant health problem and is the leading cause
      of maternal and perinatal mortality and morbidity. Low birth weight and
      prematurity are very common in pre-eclamptic mothers. Pre-eclampsia is associated
      with oxidative stress in the maternal circulation. To observe the effect of pre
      eclampsia on neonates, this study was designed to explore oxidative stress and
      anti-oxidant status in the fetal circulation in pre-eclampsia. MATERIALS AND
      METHODS: For this purpose, we collected cord bloods during delivery from
      Bangabandhu Sheikh Mujib Medical University. Twenty samples were collected from
      uncomplicated (normotensive) mothers and 15 samples were collected from pre
      eclamptic mothers (maternal age matched). Thiobarbituric acid reactive substances
      (TBARS), lipid hydroperoxide, protein carbonyl value, lipid profile, total anti
      oxidant status (TAS), vitamin C, serum total protein and albumin were measured.
      RESULTS: It was observed that TBARS and lipid hydroperoxide were significantly (P
      < 0.001) increased, protein carbonyl content were also significantly (P < 0.001)
      increased but total anti-oxidant status (P < 0.001) and vitamin C level were
      significantly (P < 0.05) decreased in cord blood from pre-eclamptic mother
      compared to control group. Cholesterol, TG, LDL level was elevated and HDL were
      lowered in cord blood in pre-eclamptic group compared to normotensive group. In
      pre-eclamptic group, cord blood total protein, albumin and globulin level were
      significantly decreased compared to control group. CONCLUSIONS: As pre-eclampsia
      is associated with increased oxidative stress and decreased anti-oxidant status,
      the results of these investigations suggest that oxidative stress and antioxidant
      status are altered towards proatherogenic level in cord blood of pre-eclamptic
      women which may ultimately be responsible for different complications of newborn
      babies of pre-eclamptic mothers.

PMID- 19380373
TI  - Subtyping and env C2/V3 sequence analysis of HIV-1 isolated from HIV-infected
      children hospitalized in Children Hospital 1, Vietnam during 2004-2005.
AB  - A molecular epidemiological study was conducted on 104 HIV-1 strains isolated
      from HIV-infected children hospitalized in Children Hospital 1 in Ho Chi Minh
      City, Vietnam during 2004-2005. Genetic subtyping based on env C2/V3 sequences
      revealed that CRF01-AE was the sole circulating recombinant form found in this
      study. Sequence analysis of the V3 loop showed that GPGQ tetramer was the most
      common V3 loop core motif identified in the HIV-1 strains studied (89.5%). The
      findings raise great concern about HIV-infected children in Vietnam and provide
      up-to-date molecular epidemiological information of HIV-1 circulating in Vietnam
      during the study period.

PMID- 19380374
TI  - Composite RNA aptamers as functional mimics of proteins.
AB  - Individual RNA aptamers are often used to modulate the function of their target
      proteins, and multi-valent aptamers have been constructed to enhance their
      activity. To expand the utility of aptamers in manipulating and controlling
      biological processes, here we advance a general method for the design and
      construction of composite aptamers. The resulting molecular constructs resemble
      proteins in that they can form specific interactions with three or more different
      partners and be readily integrated into existing protein regulatory networks. As
      the first embodiment of this method, we created a tetra-valent aptamer that
      simultaneously binds to two molecules of the Drosophila protein B52 and two
      copies of streptavidin, thus mimicking the function of an antibody in
      immunochemical assays. We demonstrated that the performance of this 'aptabody'
      rivals that of a monoclonal antibody against B52 in these assays. While this
      study was performed in vitro and the composite aptamer we made was intended to
      mimic an existing protein, the same method can be used to accommodate arbitrary
      combinations of individual aptamers in composite molecular contexts, and these
      constructs can be delivered into living cells, where they are able to utilize
      existing cellular infrastructure for their production and processing.

PMID- 19380375
TI  - Crystal structure of the beta beta alpha-Me type II restriction endonuclease
      Hpy99I with target DNA.
AB  - The beta beta alpha-Me restriction endonuclease (REase) Hpy99I recognizes the
      CGWCG target sequence and cleaves it with unusual stagger (five nucleotide 5'
      recessed ends). Here we present the crystal structure of the specific complex of
      the dimeric enzyme with DNA. The Hpy99I protomer consists of an antiparallel beta
      barrel and two beta 4 alpha 2 repeats. Each repeat coordinates a structural zinc
      ion with four cysteine thiolates in two CXXC motifs. The beta beta alpha-Me
      region of the second beta 4 alpha 2 repeat holds the catalytic metal ion (or its
      sodium surrogate) via Asp148 and Asn165 and activates a water molecule with the
      general base His149. In the specific complex, Hpy99I forms a ring-like structure
      around the DNA that contacts DNA bases on the major and minor groove sides via
      the first and second beta 4 alpha 2 repeats, respectively. Hpy99I interacts with
      the central base pair of the recognition sequence only on the minor groove side,
      where A:T resembles T:A and G:C is similar to C:G. The Hpy99I-DNA co-crystal
      structure provides the first detailed illustration of the beta beta alpha-Me site
      in REases and complements structural information on the use of this active site
      motif in other groups of endonucleases such as homing endonucleases (e.g. I-PpoI)
      and Holliday junction resolvases (e.g. T4 endonuclease VII).

PMID- 19380376
TI  - Low-fidelity DNA synthesis by the L979F mutator derivative of Saccharomyces
      cerevisiae DNA polymerase zeta.
AB  - To probe Pol zeta functions in vivo via its error signature, here we report the
      properties of Saccharomyces cerevisiae Pol zeta in which phenyalanine was
      substituted for the conserved Leu-979 in the catalytic (Rev3) subunit. We show
      that purified L979F Pol zeta is 30% as active as wild-type Pol zeta when
      replicating undamaged DNA. L979F Pol zeta shares with wild-type Pol zeta the
      ability to perform moderately processive DNA synthesis. When copying undamaged
      DNA, L979F Pol zeta is error-prone compared to wild-type Pol zeta, providing a
      biochemical rationale for the observed mutator phenotype of rev3-L979F yeast
      strains. Errors generated by L979F Pol zeta in vitro include single-base
      insertions, deletions and substitutions, with the highest error rates involving
      stable misincorporation of dAMP and dGMP. L979F Pol zeta also generates multiple
      errors in close proximity to each other. The frequency of these events far
      exceeds that expected for independent single changes, indicating that the first
      error increases the probability of additional errors within 10 nucleotides. Thus
      L979F Pol zeta, and perhaps wild-type Pol zeta, which also generates clustered
      mutations at a lower but significant rate, performs short patches of processive,
      error-prone DNA synthesis. This may explain the origin of some multiple clustered
      mutations observed in vivo.

PMID- 19380377
TI  - Local and global effects of strong DNA bending induced during molecular dynamics
      simulations.
AB  - DNA bending plays an important role in many biological processes, but its
      molecular and energetic details as a function of base sequence remain to be fully
      understood. Using a recently developed restraint, we have studied the controlled
      bending of four different B-DNA oligomers using molecular dynamics simulations.
      Umbrella sampling with the AMBER program and the recent parmbsc0 force field
      yield free energy curves for bending. Bending 15-base pair oligomers by 90
      degrees requires roughly 5 kcal mol(-1), while reaching 150 degrees requires of
      the order of 12 kcal mol(-1). Moderate bending occurs mainly through coupled base
      pair step rolls. Strong bending generally leads to local kinks. The kinks we
      observe all involve two consecutive base pair steps, with disruption of the
      central base pair (termed Type II kinks in earlier work). A detailed analysis of
      each oligomer shows that the free energy of bending only varies quadratically
      with the bending angle for moderate bending. Beyond this point, in agreement with
      recent experiments, the variation becomes linear. An harmonic analysis of each
      base step yields force constants that not only vary with sequence, but also with
      the degree of bending. Both these observations suggest that DNA is mechanically
      more complex than simple elastic rod models would imply.

PMID- 19380378
TI  - Kinetics and thermodynamics of DNA hybridization on gold nanoparticles.
AB  - Hybridization of single-stranded DNA immobilized on the surface of gold
      nanoparticles (GNPs) into double stranded DNA and its subsequent dissociation
      into ssDNA were investigated. Melting curves and rates of dissociation and
      hybridization were measured using fluorescence detection based on hybridization
      induced fluorescence change. Two distribution functions, namely the state
      distribution and the rate distribution, were proposed in order to take
      interfacial heterogeneity into account and to quantitatively analyze the data.
      Reaction and activation enthalpies and entropies of DNA hybridization and
      dissociation on GNPs were derived and compared with the same quantities in
      solution. Our results show that the interaction between GNPs and DNA reduces the
      energetic barrier and accelerates the dissociation of adhered DNA. At low surface
      densities of ssDNA adhered to GNP surface, the primary reaction pathway is that
      ssDNA in solution first adsorbs onto the GNP, and then diffuses along the surface
      until hybridizing with an immobilized DNA. We also found that the secondary
      structure of a DNA hairpin inhibits the interaction between GNPs and DNA and
      enhances the stability of the DNA hairpin adhered to GNPs.

PMID- 19380379
TI  - Molecular genetics and comparative genomics reveal RNAi is not functional in
      malaria parasites.
AB  - Techniques for targeted genetic disruption in Plasmodium, the causative agent of
      malaria, are currently intractable for those genes that are essential for blood
      stage development. The ability to use RNA interference (RNAi) to silence gene
      expression would provide a powerful means to gain valuable insight into the
      pathogenic blood stages but its functionality in Plasmodium remains
      controversial. Here we have used various RNA-based gene silencing approaches to
      test the utility of RNAi in malaria parasites and have undertaken an extensive
      comparative genomics search using profile hidden Markov models to clarify whether
      RNAi machinery exists in malaria. These investigative approaches revealed that
      Plasmodium lacks the enzymology required for RNAi-based ablation of gene
      expression and indeed no experimental evidence for RNAi was observed. In its
      absence, the most likely explanations for previously reported RNAi-mediated
      knockdown are either the general toxicity of introduced RNA (with global down
      regulation of gene expression) or a specific antisense effect mechanistically
      distinct from RNAi, which will need systematic analysis if it is to be of use as
      a molecular genetic tool for malaria parasites.

PMID- 19380380
TI  - Hypoxic injury during neonatal development in murine brain: correlation between
      in vivo DTI findings and behavioral assessment.
AB  - Preterm birth results in significant neurodevelopmental disability. A neonatal
      rodent model of chronic sublethal hypoxia (CSH), which mimics effects of preterm
      birth, was used to characterize neurodevelopmental consequences of prolonged
      exposure to hypoxia using tissue anisotropy measurements from diffusion tensor
      imaging. Corpus callosum, cingulum, and fimbria of the hippocampus revealed
      subtle, yet significant, hypoxia-induced modifications during maturation (P15
      P51). Anisotropy differences between control and CSH mice were greatest at older
      ages (>P40) in these regions. Neither somatosensory cortex nor caudate putamen
      revealed significant differences between control and CSH mice at any age. We
      assessed control and CSH mice using tests of general activity and cognition for
      behavioral correlates of morphological changes. Open-field task revealed greater
      locomotor activity in CSH mice early in maturation (P16-P18), whereas by
      adolescence (P40-P45) differences between control and CSH mice were
      insignificant. These results may be associated with lack of cortical and
      subcortical anisotropy differences between control and CSH mice. Spatial-delayed
      alternation and free-swim tasks in adulthood revealed lasting impairments for CSH
      mice in spatial memory and behavioral laterality. These differences may correlate
      with anisotropy decreases in hippocampal and callosal connectivities of CSH mice.
      Thus, CSH mice revealed developmental and behavioral deficits that are similar to
      those observed in low birth weight preterm infants.

PMID- 19380381
TI  - How smoke-free laws improve air quality: a global study of Irish pubs.
AB  - INTRODUCTION: The present study examined indoor air quality in a global sample of
      smoke-free and smoking-permitted Irish pubs. We hypothesized that levels of
      respirable suspended particles, an important marker of secondhand smoke, would be
      significantly lower in smoke-free Irish pubs than in pubs that allowed smoking.
      METHODS: Indoor air quality was assessed in 128 Irish pubs in 15 countries
      between 21 January 2004 and 10 March 2006. Air quality was evaluated using an
      aerosol monitor, which measures the level of fine particle (PM(2.5)) pollution in
      the air. A standard measurement protocol was used by data collectors across study
      sites. RESULTS: Overall, the level of air pollution inside smoke-free Irish pubs
      was 93% lower than the level found in pubs where smoking was permitted.
      DISCUSSION: Levels of indoor air pollution can be massively reduced by enacting
      and enforcing smoke-free policies.

PMID- 19380382
TI  - Effects of acute nicotine on event-related potential and performance indices of
      auditory distraction in nonsmokers.
AB  - INTRODUCTION: Although nicotine has been purported to enhance attentional
      processes, this has been evidenced mostly in tasks of sustained attention, and
      its effects on selective attention and attentional control under conditions of
      distraction are less convincing. METHODS: This study investigated the effects of
      nicotine on distractibility in 21 (11 males) nonsmokers with event-related
      potentials (ERPs) and behavioral performance measures extracted from an auditory
      discrimination task requiring a choice reaction time response to short- and long
      duration tones, with and without imbedded deviants. Administered in a randomized,
      double-blind, placebo-controlled crossover design, nicotine gum (6 mg) failed to
      counter deviant-elicited behavioral distraction characterized by longer reaction
      times and increased response errors. RESULTS: Of the deviant-elicited ERP
      components, nicotine did not alter the P3a-indexed attentional switching to the
      deviant, but in females, it tended to diminish the automatic processing of the
      deviant as shown by a smaller mismatch negativity component, and it attenuated
      attentional reorienting following deviant-elicited distraction, as reflected by a
      reduced reorienting negativity ERP component. DISCUSSION: Results are discussed
      in relation to attentional models of nicotine and with respect to future research
      directions.

PMID- 19380383
TI  - Smoke-free policies and the social acceptability of smoking in Uruguay and
      Mexico: findings from the International Tobacco Control Policy Evaluation
      Project.
AB  - INTRODUCTION: Little research has been conducted to determine the psychosocial
      and behavioral impacts of smoke-free policies in middle-income countries.
      METHODS: Cross-sectional data were analyzed from the 2006 waves of the
      International Tobacco Control Policy Evaluation. Survey comparing adult smokers
      in Mexico (n = 1,080), where smoke-free legislation at that time was weak, and
      Uruguay (n = 1,002), where comprehensive smoke-free legislation was implemented.
      Analyses aimed to determine whether exposure to smoke-free policies and perceived
      antismoking social norms were associated with smokers' receiving cues about the
      bothersome nature of secondhand smoke (SHS), with smokers' reactance against such
      cues, and with smokers' level of support for smoke-free policies in different
      venues. RESULTS: In bivariate analyses, Uruguayan smokers were more likely than
      Mexican smokers to experience verbal anti-SHS cues, lower reactance against anti
      SHS cues, stronger antismoking societal norms, and stronger support for 100%
      smoke-free policies in enclosed workplaces, restaurants, and bars. In
      multivariate models for both countries, the strength of voluntary smoke-free
      policies at home was independently associated with support for smoke-free
      policies across all venues queried, except for in bars among Uruguayans.
      Perceived strength of familial antismoking norms was consistently associated with
      all indicators of the social acceptability of smoking in Uruguay but only with
      the frequency of receiving anti-SHS verbal cues in Mexico. DISCUSSION: These
      results are generally consistent with previous research indicating that
      comprehensive smoke-free policies are likely to increase the social
      unacceptability of smoking and that resistance against such policies is likely to
      diminish once such policies are in place.

PMID- 19380385
TI  - The effect of weight loss on anti-Mullerian hormone levels in overweight and
      obese women with polycystic ovary syndrome and reproductive impairment.
AB  - BACKGROUND: Anti-Mullerian hormone (AMH) has been proposed as a clinical
      predictor of improvements in reproductive function following weight loss in
      overweight and obese women with polycystic ovary syndrome (PCOS). This study
      aimed to assess whether baseline and/or change in AMH levels with weight loss
      predict improvements in reproductive function in overweight and obese women with
      PCOS. METHODS: Fifty-two overweight and obese women with PCOS and reproductive
      impairment (age 29.8 +/- 0.8 years, BMI 36.5 +/- 0.7 kg/m(2)) followed a 20-week
      weight loss programme. AMH, weight, menstrual cyclicity and ovulatory function
      were assessed at baseline and post-intervention. RESULTS: Participants who
      responded with improvements in reproductive function (n = 26) had lower baseline
      AMH levels (23.5 +/- 3.7 versus 32.5 +/- 2.9 pmol/l; P = 0.03) and experienced
      greater weight loss (-11.7 +/- 1.2 versus -6.4 +/- 0.9 kg; P = 0.001) compared
      with those who did not respond (n = 26). Logistic regression analysis showed that
      weight loss and baseline AMH were independently related to improvements in
      reproductive function (P = 0.002 and P = 0.013, respectively). AMH levels did not
      change with weight loss in both responders and non-responders. CONCLUSIONS: In
      overweight and obese women with PCOS and reproductive dysfunction, a 20-week
      weight loss intervention resulted in improvements in reproductive function but no
      change in AMH levels. CLINICAL TRIALS REGISTRATION NUMBER: ACTRN12606000198527.

PMID- 19380384
TI  - Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3+
      regulatory T cells.
AB  - Recent studies have suggested that statins, the inhibitors for 3-hydroxy-3
      methyglutaryl (HMG)-CoA reductase in the mevalonate pathway, exhibit anti
      inflammatory effects. However, the immune modulatory effects of statins on the
      differentiation of CD4(+) T cells and their underlying mechanisms are still
      largely unknown. To address these issues, we examined the effect of simvastatin
      and inhibitors for protein farnesylation and geranylgeranylation on the
      differentiation of IL-17-producing T cells (T(h)17 cells) and Foxp3(+) CD4(+) T
      cells. Simvastatin inhibited the differentiation of T(h)17 cells through the
      inhibition of HMG-CoA reductase activity but enhanced the differentiation of
      Foxp3(+) CD4(+) T cells. Geranylgeranyltransferase I inhibitor, GGTI-298, but not
      farnesyltransferase inhibitor, FTI-277, mimicked the effects of simvastatin,
      indicating that the inhibition of protein geranylgeranylation is responsible for
      the effects. Moreover, Foxp3(+) CD4(+) T cells developed in the presence of
      transforming growth factor-beta and GGTI-298 functioned as regulatory T cells
      (Tregs) in in vitro T cell proliferation assay as well as in an autoimmune
      colitis model. Finally, GGTI-298 induced SOCS3 expression and inhibited IL-6
      induced signal transducers and activators of transcription3 phosphorylation in
      CD4(+) T cells. Taken together, these results indicate that protein
      geranylgeranylation enhances the differentiation of T(h)17 cells and inhibits the
      differentiation of Foxp3(+) Tregs partly via the inhibition of SOCS3 expression.

PMID- 19380386
TI  - Centromere-specific multicolour fluorescence in situ hybridization on human
      spermatocyte I and II metaphases.
AB  - BACKGROUND: Most meiotic studies in metaphase spermatocytes have been carried out
      with classic cytogenetic techniques. The aim of this work was to adjust the
      centromere-specific multicolour fluorescence in situ hybridization (cenM-FISH)
      procedure to spermatocyte metaphases I and II in order to improve the
      identification of meiotic chromosome abnormalities. METHODS: A total of 168
      spermatocytes I and 66 spermatocytes II from two fertile males have been studied
      using cenM-FISH. RESULTS: The mean frequency of meiotic abnormalities (synaptic,
      numerical and structural errors) found in metaphases I and II was 22.1 and 3.0%,
      respectively. The cenM-FISH technique has not only enabled the individual
      identification of chromosomes involved in meiotic disorders, but also increased
      the number of analysable cells, principally at metaphase II stage. CONCLUSIONS:
      CenM-FISH is a useful tool to study the meiotic chromosomal disorders and
      mechanisms leading to chromosomally abnormal spermatozoa.

PMID- 19380387
TI  - Commentary on "EVAR for the treatment of ruptured AAA".

PMID- 19380388
TI  - Commentary on "fenestrated grafts or debranching procedures for complex abdominal
      aortic aneurysms".

PMID- 19380389
TI  - Commentary on "update on venous procedures performed in the office setting".

PMID- 19380390
TI  - Commentary on "femoral arterial access management for endovascular aortic
      aneurysm repair: evolution and outcome".

PMID- 19380391
TI  - Dialysis access steal syndromes.
AB  - Dialysis-associated steal syndromes remain a vexing problem for the busy vascular
      access surgeon. Those factors associated with ischemia include the elderly,
      diabetic, female, preexisting cardiac disease and brachial anastomosis, and
      previous ipsilateral access. A constellation of symptoms and findings based on
      underlying arterial disease and flow characteristics are necessary to provide
      prompt diagnosis and initiate treatment. Although a digital brachial index (DBI)
      >1 and transcutaneous oxygen tension (TCPO(2) ) measurements >60 mm Hg accurately
      predict a patient not at risk, no DBI or TCPO2 levels below that accurately
      predict if a patient will develop dialysis-associated ischemia. The goal of the
      vascular access surgeon is to provide prompt recognition and treatment of the
      disorder to maximize both limb salvage and access salvage. Continuation of angio
      access in the same extremity can be accomplished in most individuals.

PMID- 19380392
TI  - Techniques to enhance arteriovenous fistula maturation.
AB  - Maturation of an arteriovenous fistula remains an elusive step in obtaining a
      good functional hemodialysis access outcome. Considerable variability in the
      performance of access procedures exists between surgical practices that are not
      necessarily well justified. Herein, a brief overview of techniques is presented
      to help in maximize the potential for maturing an arteriovenous fistula. These
      include arm vein preservation, arm vein duplex mapping, branch ligation, staged
      transposition/ superficialization, and comprehensive follow-up and intervention
      program. Although definitive data may be lacking to show effectiveness in all
      areas reviewed, recommendations are made to help surgeons in working toward
      higher maturation rates. Further opportunities avail to developing clinical
      practice guidelines so as to give all end stage renal disease patients the best
      clinical experience.

PMID- 19380393
TI  - Endovascular abdominal aortic aneurysm repair versus open repair: why and why
      not?
AB  - Randomized clinical trials have documented clinical equipoise when comparing
      endovascular abdominal aortic aneurysm repair (EVAR) with open aneurysm repair
      (OAR). Studies using large administrative databases in the United States have
      documented a trend whereby the majority of patients undergoing elective abdominal
      aortic aneurysm (AAA) repair in the United States are being repaired using
      endovascular techniques. However, few specific guidelines, outside of anatomic
      criteria for EVAR, exist to aid the physician in determining which approach is
      best for the individual patient. Variables to be considered in order to determine
      which approach is best for the patient who requires an AAA repair include age and
      comorbidities, arterial anatomy, and provider characteristics.

PMID- 19380394
TI  - Commentary on "endovascular abdominal aortic aneurysm repair versus open repair:
      why and why not?".

PMID- 19380395
TI  - Differential display mediated cloning of anthocyanidin reductase gene from tea
      (Camellia sinensis) and its relationship with the concentration of epicatechins.
AB  - Tea [Camellia sinensis (L.) O. Kuntze] leaves are a major source of epicatechin
      (EC) and its gallolyl derivatives epicatechin gallate, epigallocatechin and
      epigallocatechin gallate, collectively known as epicatechins (ECs). Epicatechins
      are important factors determining tea quality, and they also possess many
      medicinal properties. To gain further information about the regulation of the
      biosynthesis of ECs, we cloned the gene encoding anthocyanidin reductase from tea
      (CsANR) by first quantifying changes in the concentrations of ECs in response to
      drought, gibberellic acid (GA(3)), abscisic acid (ABA) and wounding treatments,
      followed by differential display of mRNAs and analysis of those bands exhibiting
      a change in expression paralleling the treatment-induced changes observed in the
      EC data. Analysis of 133 bands yielded a partial cDNA of CsANR that was later
      cloned to the full length by rapid amplification of the cDNA ends. The full
      length CsANR (Accession No. AY641729) comprised 1233 bp with an ORF of 1014 bp
      (from 79 to 1092 bp) encoding a polypeptide of 337 amino acids. Expression of
      CsANR in an Escherichia coli expression vector yielded a functional protein that
      catalyzed the conversion of cyanidin to EC in the presence of NADPH. Analysis of
      ECs and gene expression in leaves at different developmental stages and across
      five tea clones exhibiting variable concentrations of ECs revealed a positive
      correlation between concentration of ECs and CsANR expression. Expression of
      CsANR was down-regulated in response to drought, ABA and GA(3) treatments and up
      regulated in response to wounding.

PMID- 19380396
TI  - Matching supply and demand for blood in Guizhou province, China: an unresolved
      challenge.
AB  - BACKGROUND: Problems with blood supply in China in the 1990s stimulated measures
      to achieve 100% voluntary donation but supply remains inadequate to meet demand.
      STUDY DESIGN AND METHODS: Review of official policies, supplemented with
      observation of practice and interviews with key informants (potential and actual
      donors and health workers) in Guizhou province in Southern China. RESULTS:
      Interviewees perceived the transfusion system as a mutual social contract.
      However, some individuals were unwilling to donate because of concerns about
      health risks, the idea of transferring blood between people, wastage or profits
      being made from blood. Inappropriate incentives, including cash, were used to
      encourage donation. Recent reforms have increased confidence in donation and
      transfusion safety although concerns persist about misuse. There is a need to
      reduce unnecessary use of blood and its products. CONCLUSION: China still relies
      heavily on blood supplies obtained through quota, purchase or use of incentives.
      There is scope to expand voluntary donation further. However, as a priority it
      will be necessary to reduce overuse.

PMID- 19380397
TI  - Communicable disease and health protection quarterly review: January to March
      2009.

PMID- 19380400
TI  - FDA puts restrictions on an institutional review board after secret
      investigation.

PMID- 19380401
TI  - New funding mechanism is launched to combat malaria.

PMID- 19380403
TI  - Assessing tumor response to therapy.
AB  - Most anticancer drugs are effective only in subgroups of patients, and our
      current understanding of tumor biology does not allow us to predict accurately
      which patient will benefit from a specific therapeutic regimen. Various
      techniques have, therefore, been developed for monitoring tumor response to
      therapy, but measuring tumor shrinkage on CT represents the current standard.
      Although response assessment on CT has been refined over many years, fundamental
      limitations remain. Interobserver variability in tumor size measurements is still
      high because of difficulties in delineating tumor tissue from secondary changes
      in the surrounding tissues. Furthermore, CT is inaccurate in differentiating
      viable tumor from necrotic or fibrotic tissue. Consequently, the degree of
      response may be underestimated on CT. Conversely, if tumor shrinkage is short
      lived and followed by rapid tumor regrowth, CT may overestimate the beneficial
      effects of a treatment. Finally, CT is limited in characterizing responses in
      tumors that do not change in size during therapy. Because the growth rate of
      untreated human tumors varies tremendously, an unchanged tumor size after some
      weeks of therapy may represent a drug effect but may also indicate a slowly
      growing tumor that was not affected by the applied therapy. Molecular imaging
      with PET and the glucose analogue (18)F-FDG PET has been shown to improve
      response assessment in several tumor types. In malignant lymphoma, international
      criteria for monitoring response to therapy have recently been revised, and the
      (18)F-FDG signal now plays a central role in defining tumor response. In a
      variety of solid tumors, single-center studies have indicated that (18)F-FDG PET
      may provide earlier or more accurate assessment of tumor response than CT,
      suggesting that (18)F-FDG PET could play a significant role in personalizing the
      treatment of malignant tumors. However, generally accepted criteria for response
      assessment in solid tumors are missing, which makes it frequently impossible to
      compare the results of different studies. International guidelines and criteria
      for response assessment by (18)F-FDG PET in solid tumors are, therefore, eagerly
      awaited.

PMID- 19380405
TI  - Standards for PET image acquisition and quantitative data analysis.
AB  - Quantitative (18)F-FDG PET is increasingly being recognized as an important tool
      for diagnosis, determination of prognosis, and response monitoring in oncology.
      However, PET quantification with, for example, standardized uptake values (SUVs)
      is affected by many technical and physiologic factors. As a result, some of the
      variations in the literature on SUV-based patient outcomes are explained by
      differences in (18)F-FDG PET study methods. Various technical and clinical
      studies have been performed to understand the factors affecting PET
      quantification. On the basis of the results of those studies, several
      recommendations and guidelines have been proposed with the aims of improving the
      image quality and the quantitative accuracy of (18)F-FDG PET studies. In this
      contribution, an overview of recommendations and guidelines for quantitative
      (18)F-FDG PET studies in oncology is provided. Special attention is given to the
      rationale underlying certain recommendations and to some of the differences in
      various guidelines.

PMID- 19380406
TI  - 18F-FDG PET and 18F-FDG PET/CT for assessing response to therapy in esophageal
      cancer.
AB  - In patients with locally advanced esophageal cancer, preoperative chemotherapy or
      chemoradiotherapy has been shown to improve outcome with respect to survival.
      Patients who respond to induction therapy have a significantly improved survival,
      compared with patients who do not respond to the therapy. However, surrogate
      markers that predict response or prognosis-especially early in the course of
      therapy-are not available in clinical routine. In patients with esophageal
      cancer, PET with the glucose analog (18)F-FDG can be used for assessing response
      to therapy. Therapy response can be assessed with (18)F-FDG PET and (18)F-FDG
      PET/CT late, that is, after completion of therapy, and early in the course of
      therapy. In adenocarcinomas of the esophagogastric junction, (18)F-FDG has been
      established and validated in several studies as a surrogate marker that allows
      prediction of response and prognosis, whereas in other studies (18)F-FDG PET was
      not predictive of response and prognosis. The MUNICON study was an initial
      unicenter trial showing that a PET-guided treatment algorithm was feasible in
      patients with adenocarcinomas of the esophagogastric junction. The results of
      this study are important toward individualization of multimodal treatment. The
      use of (18)F-FDG PET and PET/CT for therapy monitoring in esophageal cancer is
      the subject of intense discussion, underlining the need for randomized
      multicenter studies. From a methodologic point of view, the most important issue
      in therapy monitoring using (18)F-FDG PET and PET/CT is the standardization of
      patient preparation, data acquisition and processing, and data interpretation,
      especially for prospective randomized multicenter studies. In conclusion, single
      center studies investigating response assessment in patients with esophageal
      cancer have provided promising results. In the future, prospective randomized
      multicenter trials will have to be performed and research will address new
      imaging probes and innovative therapy regimens.

PMID- 19380404
TI  - Radiopharmaceuticals in preclinical and clinical development for monitoring of
      therapy with PET.
AB  - This review article discusses PET agents, other than (18)F-FDG, with the
      potential to monitor the response to therapy before, during, or after therapeutic
      intervention. This review deals primarily with non-(18)F-FDG PET tracers that are
      in the final stages of preclinical development or in the early stages of clinical
      application for monitoring the therapeutic response. Four sections related to the
      nature of the tracers are included: radiotracers of DNA synthesis, such as the 2
      most promising agents, the thymidine analogs 3'-(18)F-fluoro-3'-deoxythymidine
      and (18)F-1-(2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl)thymine; agents for PET
      imaging of hypoxia within tumors, such as (60/62/64)Cu-labeled diacetyl-bis(N(4)
      methylthiosemicarbazone) and (18)F-fluoromisonidazole; amino acids for PET
      imaging, including the most popular such agent, l-[methyl-(11)C]methionine; and
      agents for the imaging of tumor expression of androgen and estrogen receptors,
      such as 16beta-(18)F-fluoro-5alpha-dihydrotestosterone and 16alpha-(18)F-fluoro
      17beta-estradiol, respectively.

PMID- 19380407
TI  - PET/CT for therapy response assessment in lymphoma.
AB  - PET with (18)F-FDG is a standard staging procedure for most lymphoma subtypes.
      Performed during and after therapy for Hodgkin lymphoma (HL) and aggressive non
      Hodgkin lymphoma (NHL), (18)F-FDG PET results have a high prognostic value and
      correlate with survival. (18)F-FDG PET has been incorporated into revised
      response criteria for aggressive lymphomas, and several ongoing trials are under
      way to investigate the value of treatment adaptation based on early (18)F-FDG PET
      results for HL and aggressive NHL. There is little evidence to support the use of
      (18)F-FDG PET for monitoring of the treatment of indolent lymphomas and for
      routine use in the surveillance setting. So that trial results can be compared
      and translated easily into clinical practice, uniform and evidence-based
      guidelines for the interpretation and reporting of response monitoring scans are
      warranted. Because it is still not proven that the use of interim (18)F-FDG PET
      can improve patient outcomes, we recommend examination of the use of (18)F-FDG
      PET for response monitoring in appropriately designed clinical trials.

PMID- 19380408
TI  - PET monitoring of therapy response in head and neck squamous cell carcinoma.
AB  - In the Western world, more than 90% of head and neck cancers are head and neck
      squamous cell carcinomas (HNSCCs). The most appropriate treatment approach for
      HNSCC varies with the disease stage and disease site in the head and neck.
      Concurrent chemoradiotherapy has become a widely used means for the definitive
      treatment of locoregionally advanced HNSCC. Although this multimodality treatment
      provides higher response rates than radiotherapy alone, the detection of residual
      viable tumor after the end of therapy remains an important issue and is one of
      the major applications of (18)F-FDG PET. Studies have shown that negative (18)F
      FDG PET or PET/CT results after concurrent chemoradiotherapy have a high negative
      predictive value (>95%), whereas the positive predictive value is only about 50%.
      However, when applied properly, FDG PET/CT can exclude residual disease in most
      patients, particularly patients with residual enlarged lymph nodes who would
      otherwise undergo neck dissection. In contrast to other malignancies, data are
      limited on the utility of (18)F-FDG PET for monitoring the response to induction
      chemotherapy in HNSCC or for assessing treatment response early during the course
      of definitive chemoradiotherapy. The proliferation marker (18)F-3'-deoxy
      3'fluorothymidine is currently under study for this purpose. Beyond standard
      chemotherapy, newer treatment regimens in HNSCC take advantage of our improved
      understanding of tumor biology. Two molecules important in the progression of
      HNSCC are the epidermal growth factor receptor and the vascular endothelial
      growth factor (VEGF) and its receptor VEGF-R. Drugs attacking these molecules are
      now under study for HNSCC. PET probes have been developed for imaging the
      presence of these molecules in HNSCC and their inhibition by specific drug
      interaction; the relevance of these probes for response assessment in HNSCC will
      be discussed. Hypoxia is a common phenomenon in HNSCC and renders cancers
      resistant to chemo- and radiotherapy. Imaging and quantification of hypoxia with
      PET probes is under study and may become a prerequisite for overcoming chemo- and
      radioresistance using radiosensitizing drugs or hypoxia-directed irradiation
      techniques and for monitoring the response to these techniques in selected groups
      of patients. Although (18)F-FDG PET/CT will remain the major clinical tool for
      monitoring treatment in HNSCC, other PET probes may have a role in identifying
      patients who are likely to benefit from treatment strategies that include
      biologic agents such as epidermal growth factor receptor inhibitors or VEGF
      inhibitors.

PMID- 19380409
TI  - The role of 18F-FDG PET in assessing therapy response in cancer of the cervix and
      ovaries.
AB  - For locally advanced cervical cancer, the current literature supports the use of
      (18)F-FDG PET for assessing treatment response 3 mo after the completion of
      concurrent chemoradiation. (18)F-FDG PET can provide reliable long-term
      prognostic information for these patients and, in the future, may be used to
      guide additional therapy. Investigational areas include the use of (18)F-FDG PET
      for monitoring response during radiotherapy and chemotherapy in the metastatic
      and neoadjuvant settings. For ovarian masses, the performance of (18)F-FDG PET in
      the detection of borderline tumors is limited, and the presence of physiologic
      (18)F-FDG uptake in normal ovaries of premenopausal women poses another
      limitation. Preliminary data suggest that the performance of (18)F-FDG PET and
      (18)F-FDG PET/CT is superior to that of CT alone in initial staging, but the
      sensitivity of both in the detection of carcinomatosis is limited. Preliminary
      data also suggest that (18)F-FDG PET may be promising for early prediction of
      response to chemotherapy and for prediction of response after the completion of
      chemotherapy. (18)F-FDG PET and (18)F-FDG PET/CT are most helpful in the
      evaluation of patients with suspected recurrent ovarian carcinoma, especially
      when CA-125 levels are rising and CT findings are normal or equivocal. PET and CT
      are complementary, and PET/CT should be used when available. Preliminary data
      suggest that the addition of (18)F-FDG PET/CT to the evaluation of these patients
      changes management in approximately a third and reduces overall treatment costs
      by accurately identifying patients who will or will not benefit from surgery.

PMID- 19380410
TI  - Response to therapy in breast cancer.
AB  - Increasing numbers of patients with newly diagnosed breast cancer receive primary
      systemic therapy followed by surgery. Histopathology provides an accurate
      assessment of treatment efficacy on the basis of the extent of residual tumor and
      regressive changes within tumor tissue. However, only approximately 20% of breast
      cancer patients achieve a pathologic complete response, a fact that necessitates
      methods for monitoring therapeutic effectiveness early during therapy. (18)F-FDG
      PET and (18)F-FDG PET/CT provide essential information regarding a response to
      primary chemotherapy. Patients with low tumor metabolic activity on pretreatment
      (18)F-FDG PET are not likely to achieve a histopathologic response. The degree of
      changes in (18)F-FDG uptake after the initiation of therapy is correlated with
      the histopathologic response after the completion of therapy. Thus, tumor
      metabolic changes assessed early during therapy predict therapeutic effectiveness
      in individual patients. Early identification of ineffective therapy also might be
      helpful in patients with metastatic breast cancer because many palliative
      treatment options are available. Changes in metabolic activity generally occur
      earlier than changes in tumor size, which is the current standard for the
      assessment of a response. Although treatment stratification based on a metabolic
      response is an exciting potential application of PET, specific PET response
      assessment criteria still need to be developed and validated on the basis of
      patient outcomes before changes in treatment regimens can be implemented. There
      is increasing clinical evidence for metastatic breast cancer and other tumors
      that (18)F-FDG PET/CT is the most accurate imaging procedure for assessment of
      the response at the end of treatment when both CT information and tumor metabolic
      activity are considered. Importantly, in the setting of primary chemotherapy,
      neither PET/CT nor conventional imaging procedures can assess the extent of
      residual breast cancer as accurately as histopathology. Observation of changes in
      tumor blood flow or tumor cell proliferation is an additional encouraging
      approach for predicting a response. Ultimately, the prediction of therapeutic
      effectiveness by PET and PET/CT could help to individualize treatment and to
      avoid ineffective chemotherapies, with their associated toxicities.

PMID- 19380411
TI  - Role of 18F-FDG PET in assessment of response in non-small cell lung cancer.
AB  - Despite recognized limitations, structural imaging with CT remains the standard
      technique for evaluating the response of lung cancer to both chemotherapy and
      radiotherapy. This evaluation has become increasingly important with the advent
      of neoadjuvant therapy before surgery. The high uptake of (18)F-FDG in most lung
      cancers and the demonstration that successful treatment reduces uptake have led
      to increasing enthusiasm for the use of PET and PET/CT to assess the therapeutic
      response. In this review, theoretic considerations and current evidence
      supporting the role of (18)F-FDG PET are discussed.

PMID- 19380412
TI  - Excluding serious illness in feverish children in primary care: restricted rule
      out method for diagnosis.

PMID- 19380414
TI  - Diagnostic strategies used in primary care.

PMID- 19380416
TI  - The tight junction protein ZO-2 mediates proliferation of vascular smooth muscle
      cells via regulation of Stat1.
AB  - AIMS: Recent evidence suggests that the zonula occludens protein 2 (ZO-2) might
      have additional cellular functions, beyond regulation of paracellular
      permeability of epithelial and endothelial cells. Deregulation of ZO-2 in
      response to ischaemia, hypertensive stress, and vascular injury implies its
      involvement in cardiovascular disorders, most likely via regulating the
      functional behaviour of vascular smooth muscle cells (VSMC). However, a role of
      ZO-2 in VSMC biology has yet to be established. Our study was designed to
      understand the specific functions of ZO-2 in human VSMC. METHODS AND RESULTS: The
      expression of ZO-2 and Stat1 upon vascular injury was studied using ex vivo organ
      culture of coronary arteries combined with immunohistochemistry. ZO-2 silencing
      in human primary VSMC was achieved by means of lentiviral gene transfer. Cell
      proliferation was assessed by analysing DNA synthesis and by cell counting. Stat1
      expression was examined using immunoblotting, immunocytochemistry, TaqMan, and
      fluorescence activated cell sorting (FACS) analysis. Functional relevance of
      Stat1 up-regulation was studied using a Stat1 promoter-luciferase reporter assay
      and intracellular microinjections of a Stat1 specific antibody. ZO-2 was highly
      expressed in the media and neointima of dilated but not of control arteries,
      whereas expression of the transcription factor Stat1 was inversely regulated upon
      injury. Analysis of VSMC with down-regulated ZO-2 revealed increased expression
      of Stat1 in these cells, whereas Stat1 phosphorylation was not affected. Stat1 up
      regulation in VSMC with ZO-2 silencing resulted in a coordinate activation of
      Stat1-specific genes and consequently led to inhibition of cell proliferation.
      This effect was restored by microinjection of a Stat1 neutralising antibody.
      CONCLUSION: Our data suggest that the tight junction protein ZO-2 is involved in
      regulation of VSMC growth control upon vascular injury that is mediated by the
      transcription factor Stat1. Our findings point to a novel function of ZO-2 in
      VSMC and implicate ZO-2 as a novel important molecular target in pathological
      states of vascular remodelling in cardiovascular diseases.

PMID- 19380417
TI  - ACE inhibition promotes upregulation of endothelial progenitor cells and
      neoangiogenesis in cardiac pressure overload.
AB  - AIMS: Inhibition of the angiotensin-converting enzyme (ACE) prevents maladaptive
      cardiac remodelling. Endothelial progenitor cells (EPC) from the bone marrow
      contribute to endothelial repair and neovascularization, effects that are
      potentially important during cardiac remodelling. We hypothesized that ACE
      inhibitors may exert beneficial effects during pressure-induced myocardial
      hypertrophy by regulating progenitor cell function. METHODS AND RESULTS: In
      C57/Bl6 mice, development of cardiac hypertrophy induced by transaortic
      constriction (TAC) for 5 weeks was reduced by ramipril, 5 mg/kg p.o., independent
      of blood pressure lowering. Ramipril prevented TAC-induced apoptosis of cardiac
      myocytes and endothelial cells. On day 1 after TAC, upregulation of Sca
      1(pos)/KDR(pos) EPC was observed, which was further increased by ramipril. EPC
      were persistently elevated in the TAC mice receiving vehicle treatment but not in
      the ramipril group after 5 weeks. These effects were independent of hypoxia
      inducible factor-1alpha mRNA and protein expression. The ACE inhibitor but not
      TAC improved the migratory capacity of DiLDL(pos) EPC. Increased cardiac
      afterload induced upregulation of extracardiac neoangiogenesis. This effect was
      enhanced by ACE inhibition. Ramipril but not TAC markedly increased cardiac
      capillary density determined by the ratio of CD31(pos) cells to cardiomyocytes.
      Bone marrow transplantation studies revealed that TAC increased the percentage of
      bone marrow-derived GFP(pos) endothelial cells in the myocardium, and ramipril
      made this effect more pronounced. CONCLUSIONS: ACE inhibition prevents pressure
      induced maladaptive cardiac hypertrophy and increases intra- and extracardiac
      neoangiogenesis associated with the upregulation of EPC and amelioration of EPC
      migration. The regulation of progenitor cells from the bone marrow identifies a
      novel effect of ACE inhibitors during cardiac remodelling.

PMID- 19380418
TI  - Parstatin: a cryptic peptide involved in cardioprotection after ischaemia and
      reperfusion injury.
AB  - AIMS: Thrombin activates protease-activated receptor 1 by proteolytic cleavage of
      the N-terminus. Although much research has focused on the activated receptor,
      little is known about the 41-amino acid N-terminal peptide (parstatin). We
      hypothesized that parstatin would protect the heart against ischaemia-reperfusion
      injury. METHODS AND RESULTS: We assessed the protective role of parstatin in an
      in vivo and in vitro rat model of myocardial ischaemia-reperfusion injury.
      Parstatin treatment before, during, and after ischaemia decreased infarct size by
      26%, 23%, and 18%, respectively, in an in vivo model of ischaemia-reperfusion
      injury. Parstatin treatment immediately before ischaemia decreased infarct size
      by 65% and increased recovery in ventricular function by 23% in an in vitro
      model. We then assessed whether parstatin induced cardioprotection by activation
      of a Gi-protein-dependent pathway. Gi-protein inactivation by pertussis toxin
      completely abolished the cardioprotective effects. The cardioprotective effects
      were also abolished by inhibition of nitric oxide synthase (NOS), extracellular
      signal-regulated kinases 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38
      MAPK), and K(ATP) channels in vitro. Furthermore, parstatin increased coronary
      flow and decreased perfusion pressure in the isolated heart. The vasodilatory
      properties of parstatin were confirmed in rat coronary arterioles. CONCLUSION: A
      single treatment of parstatin administered prior to ischaemia confers immediate
      cardioprotection by recruiting the Gi-protein activation pathway including p38
      MAPK, ERK1/2, NOS, and K(ATP) channels. Parstatin exerts effects on both the
      cardiomyocytes and the coronary circulation to induce cardioprotection. This
      suggests a potential therapeutic role of parstatin in the treatment of cardiac
      injury resulting from ischaemia and reperfusion.

PMID- 19380419
TI  - Nitrogen affects cluster root formation and expression of putative peptide
      transporters.
AB  - Non-mycorrhizal Hakea actites (Proteaceae) grows in heathland where organic
      nitrogen (ON) dominates the soil nitrogen (N) pool. Hakea actites uses ON for
      growth, but the role of cluster roots in ON acquisition is unknown. The aim of
      the present study was to ascertain how N form and concentration affect cluster
      root formation and expression of peptide transporters. Hydroponically grown
      plants produced most biomass with low molecular weight ON>inorganic N>high
      molecular weight ON, while cluster roots were formed in the order no
      N>ON>inorganic N. Intact dipeptide was transported into roots and metabolized,
      suggesting a role for the peptide transporter (PTR) for uptake and transport of
      peptides. HaPTR4, a member of subgroup II of the NRT1/PTR transporter family,
      which contains most characterized di- and tripeptide transporters in plants,
      facilitated transport of di- and tripeptides when expressed in yeast. No
      transport activity was demonstrated for HaPTR5 and HaPTR12, most similar to less
      well characterized transporters in subgroup III. The results provide further
      evidence that subgroup II of the NRT1/PTR family contains functional di- and
      tripeptide transporters. Green fluorescent protein fusion proteins of HaPTR4 and
      HaPTR12 localized to tonoplast, and plasma- and endomembranes, respectively,
      while HaPTR5 localized to vesicles of unknown identity. Grown in heathland or
      hydroponic culture with limiting N supply or starved of nutrients, HaPTR genes
      had the highest expression in cluster roots and non-cluster roots, and leaf
      expression increased upon re-supply of ON. It is concluded that formation of
      cluster roots and expression of PTR are regulated in response to N supply.

PMID- 19380420
TI  - The diversity of (13)C isotope discrimination in a Quercus robur full-sib family
      is associated with differences in intrinsic water use efficiency, transpiration
      efficiency, and stomatal conductance.
AB  - (13)C discrimination in organic matter with respect to atmospheric CO(2)
      (Delta(13)C) is under tight genetic control in many plant species, including the
      pedunculate oak (Quercus robur L.) full-sib progeny used in this study.
      Delta(13)C is expected to reflect intrinsic water use efficiency, but this
      assumption requires confirmation due to potential interferences with mesophyll
      conductance to CO(2), or post-photosynthetic discrimination. In order to dissect
      the observed Delta(13)C variability in this progeny, six genotypes that have
      previously been found to display extreme phenotypic values of Delta(13)C [either
      very high ('high Delta') or low ('low Delta') phenotype] were selected, and
      transpiration efficiency (TE; accumulated biomass/transpired water), net CO(2)
      assimilation rate (A), stomatal conductance for water vapour (g(s)), and
      intrinsic water use efficiency (W(i)=A/g(s)) were compared with Delta(13)C in
      bulk leaf matter, wood, and cellulose in wood. As expected, 'high Delta'
      displayed higher values of Delta(13)C not only in bulk leaf matter, but also in
      wood and cellulose. This confirmed the stability of the genotypic differences in
      Delta(13)C recorded earlier. 'High Delta' also displayed lower TE, lower W(i),
      and higher g(s). A small difference was detected in photosynthetic capacity but
      none in mesophyll conductance to CO(2). 'High Delta' and 'low Delta' displayed
      very similar leaf anatomy, except for higher stomatal density in 'high Delta'.
      Finally, diurnal courses of leaf gas exchange revealed a higher g(s) in 'high
      Delta' in the morning than in the afternoon when the difference decreased. The
      gene ERECTA, involved in the control of water use efficiency, leaf
      differentiation, and stomatal density, displayed higher expression levels in 'low
      Delta'. In this progeny, the variability of Delta(13)C correlated closely with
      that of W(i) and TE. Genetic differences of Delta(13)C and W(i) can be ascribed
      to differences in stomatal conductance and stomatal density but not in
      photosynthetic capacity.

PMID- 19380415
TI  - Approaches to improve the diagnosis and management of infertility.
AB  - BACKGROUND Recent advances in our understanding of the causes of infertility and
      of assisted reproductive technology (ART) have led to the development of complex
      diagnostic tools, prognostic models and treatment options. The Third Evian Annual
      Reproduction (EVAR) Workshop Meeting was held on 26-27 April 2008 to evaluate
      evidence supporting current approaches to the diagnosis and management of
      infertility and to identify areas for future research efforts. METHODS Specialist
      reproductive medicine clinicians and scientists delivered presentations based on
      published literature and ongoing research on patient work-up, ovarian stimulation
      and embryo quality assessment during ART. This report is based on the expert
      presentations and subsequent group discussions and was supplemented with
      publications from literature searches and the authors' knowledge. RESULTS It was
      agreed that single embryo transfer (SET) should be used with increasing frequency
      in cycles of ART. Continued improvements in cryopreservation techniques, which
      improve pregnancy rates using supernumerary frozen embryos, are expected to
      augment the global uptake of SET. Adaptation and personalization of fertility
      therapy may help to optimize efficacy and safety outcomes for individual
      patients. Prognostic modelling and personalized management strategies based on
      individual patient characteristics may prove to represent real progress towards
      improved treatment. However, at present, there is limited good-quality evidence
      to support the use of these individualized approaches. CONCLUSIONS Greater
      quality control and standardization of clinical and laboratory evaluations are
      required to optimize ART practices and improve individual patient outcomes. Well
      designed, good-quality studies are required to drive improvements to the
      diagnosis and management of ART processes.

PMID- 19380421
TI  - Ethylene regulates phosphorus remobilization and expression of a phosphate
      transporter (PhPT1) during petunia corolla senescence.
AB  - The programmed degradation of macromolecules during petal senescence allows the
      plant to remobilize nutrients from dying to developing tissues. Ethylene is
      involved in regulating the timing of nucleic acid degradation in petunia, but it
      is not clear if ethylene has a role in the remobilization of phosphorus during
      petal senescence. To investigate ethylene's role in nutrient remobilization, the
      P content of petals (collectively called the corolla) during early development
      and senescence was compared in ethylene-sensitive wild type Petunia x hybrida
      'Mitchell Diploid' (MD) and transgenic petunias with reduced sensitivity to
      ethylene (35S::etr1-1). When compared to the total P content of corollas on the
      day of flower opening (the early non-senescing stage), P in MD corollas had
      decreased 74% by the late stage of senescence (advanced wilting). By contrast, P
      levels were only reduced by an average of 32% during etr1-1 corolla (lines 44568
      and Z00-35-10) senescence. A high-affinity phosphate transporter, PhPT1
      (PhPht1;1), was cloned from senescing petunia corollas by RT-PCR. PhPT1
      expression was up-regulated during MD corolla senescence and a much smaller
      increase was detected during the senescence of etr1-1 petunia corollas. PhPT1
      mRNA levels showed a rapid increase in detached corollas (treated at 1 d after
      flower opening) following treatment with low levels of ethylene (0.1 microl l(
      1)). Transcripts accumulated in the presence of the protein synthesis inhibitor,
      cycloheximide, indicating that PhPT1 is a primary ethylene response gene. PhPT1
      is a putative phosphate transporter that may function in Pi translocation during
      senescence.

PMID- 19380422
TI  - Pectin methylesterase NaPME1 contributes to the emission of methanol during
      insect herbivory and to the elicitation of defence responses in Nicotiana
      attenuata.
AB  - Pectin methylesterases (PMEs) catalyse the demethylation of pectin within plant
      cell walls, releasing methanol (MeOH) in the process. Thus far, PMEs have been
      found to be involved in diverse processes such as plant growth and development
      and defence responses against pathogens. Herbivore attack increases PME
      expression and activity and MeOH emissions in several plant species. To gain
      further insights into the role of PMEs in defence responses against herbivores,
      the expression of a Manduca sexta oral secretion (OS)-inducible PME in Nicotiana
      attenuata (NaPME1) was silenced by RNA interference (RNAi)-mediated gene
      silencing. Silenced lines (ir-pme) showed 50% reduced PME activity in leaves and
      70% reduced MeOH emissions after OS elicitation compared with the wild type (WT),
      demonstrating that the herbivore-induced MeOH emissions originate from the
      demethylation of pectin by PME. In the initial phase of the OS-induced jasmonic
      acid (JA) burst (first 30 min), ir-pme lines produced WT levels of this hormone
      and of jasmonyl-isoleucine (JA-Ile); however, these levels were significantly
      reduced in the later phase (60-120 min) of the burst. Similarly, suppressed
      levels of the salicylic acid (SA) burst induced by OS elicitation were observed
      in ir-pme lines even though wounded ir-pme leaves contained slightly increased
      amounts of SA. This genotype also presented reduced levels of OS-induced trypsin
      proteinase inhibitor activity in leaves and consistently increased M. sexta
      larvae performance compared with WT plants. These latter responses could not be
      recovered by application of exogenous MeOH. Together, these results indicated
      that PME contributes, probably indirectly by affecting cell wall properties, to
      the induction of anti-herbivore responses.

PMID- 19380423
TI  - Light-induced vegetative anthocyanin pigmentation in Petunia.
AB  - The Lc petunia system, which displays enhanced, light-induced vegetative
      pigmentation, was used to investigate how high light affects anthocyanin
      biosynthesis, and to assess the effects of anthocyanin pigmentation upon
      photosynthesis. Lc petunia plants displayed intense purple anthocyanin
      pigmentation throughout the leaves and stems when grown under high-light
      conditions, yet remain acyanic when grown under shade conditions. The coloured
      phenotypes matched with an accumulation of anthocyanins and flavonols, as well as
      the activation of the early and late flavonoid biosynthetic genes required for
      flavonol and anthocyanin production. Pigmentation in Lc petunia only occurred
      under conditions which normally induce a modest amount of anthocyanin to
      accumulate in wild-type Mitchell petunia [Petunia axillaris x (Petunia axillaris
      x Petunia hybrida cv. 'Rose of Heaven')]. Anthocyanin pigmentation in Lc petunia
      leaves appears to screen underlying photosynthetic tissues, increasing light
      saturation and light compensation points, without reducing the maximal
      photosynthetic assimilation rate (A(max)). In the Lc petunia system, where the
      bHLH factor Leaf colour is constitutively expressed, expression of the bHLH (Lc)
      and WD40 (An11) components of the anthocyanin regulatory system were not limited,
      suggesting that the high-light-induced anthocyanin pigmentation is regulated by
      endogenous MYB transcription factors.

PMID- 19380424
TI  - Integrating pests and pathogens into the climate change/food security debate.
AB  - While many studies have demonstrated the sensitivities of plants and of crop
      yield to a changing climate, a major challenge for the agricultural research
      community is to relate these findings to the broader societal concern with food
      security. This paper reviews the direct effects of climate on both crop growth
      and yield and on plant pests and pathogens and the interactions that may occur
      between crops, pests, and pathogens under changed climate. Finally, we consider
      the contribution that better understanding of the roles of pests and pathogens in
      crop production systems might make to enhanced food security. Evidence for the
      measured climate change on crops and their associated pests and pathogens is
      starting to be documented. Globally atmospheric [CO(2)] has increased, and in
      northern latitudes mean temperature at many locations has increased by about 1.0
      1.4 degrees C with accompanying changes in pest and pathogen incidence and to
      farming practices. Many pests and pathogens exhibit considerable capacity for
      generating, recombining, and selecting fit combinations of variants in key
      pathogenicity, fitness, and aggressiveness traits that there is little doubt that
      any new opportunities resulting from climate change will be exploited by them.
      However, the interactions between crops and pests and pathogens are complex and
      poorly understood in the context of climate change. More mechanistic inclusion of
      pests and pathogen effects in crop models would lead to more realistic
      predictions of crop production on a regional scale and thereby assist in the
      development of more robust regional food security policies.

PMID- 19380425
TI  - Expression and possible role of fibroblast growth factor family members in
      porcine antral follicles during final maturation.
AB  - The aim of this study was to investigate the possible participation of fibroblast
      growth factor (FGF) family members (FGF1, FGF2 and FGF7 and their receptors) in
      porcine follicles (polyovulatory species) under special consideration for FGF2
      during final growth. A classification of follicles was done by size and
      follicular fluid content of oestradiol-17beta, progesterone and prostaglandin
      F2alpha. The mRNA expression of examined factors was analysed by real-time PCR.
      The hormone concentration was estimated by enzyme immunoassay, protein
      characterisation by western blotting and localisation by immunohistochemistry.
      Follicle tissue separated in theca interna and granulosa cells was extracted and
      tested for mRNA of FGF1, FGF2, FGF7 and receptors (FGFR1IIIc, FGFRIIIb and
      FGFR2IIIc). Additionally, the mRNA expression of FSHR, LHR and aromatase
      cytochrome P450 for further characterisation of follicles was analysed.
      Significantly, higher FGF2 protein levels were measured in stroma when compared
      with total follicle or corpus luteum tissue. This result was confirmed by western
      blot with two strong bands. Immunological localisation of FGF2 only in stroma
      (fibroblasts) confirms the protein measurements. The results show a clear
      difference for FGF2 protein expression during final growth of follicles if
      monovulatory (bovine) and polyovulatory (porcine) species are compared. FGF2
      protein in porcine ovary may be (due to localisation and concentration in stroma)
      important for support of angiogenesis of more follicles (polyovulatory species)
      and not of a single follicle like in cows.

PMID- 19380426
TI  - Comparison of the production, quality, and in vitro maturation capacity of
      oocytes from untreated cycling and intermediate phase equine serum gonadotropin
      treated fat-tailed dunnarts (Sminthopsis crassicaudata).
AB  - This study describes ovarian changes during the natural and stimulated
      reproductive cycle of breeding (< or =12 month) and retired (>12 month) fat
      tailed dunnarts, Sminthopsis crassicaudata. Increased urinary cornified
      epithelial cells and the influx of leukocytes defined day 0, at which time the
      naturally cycling females had already ovulated; at day 16 females had no antral
      follicles, but by day 20 antral follicles had begun to develop. There was no
      difference between naturally cycling breeding and retired females. Females were
      stimulated with 1 IU equine serum gonadotropin (eSG) during the intermediate
      phase on day 16 and killed 3, 4, or 5 days later. Stimulation resulted in a
      significant increase in the number of growing antral follicles but retired
      females demonstrated a reduced response. Upon collection from breeding females 4
      days following eSG stimulation, 100% of oocytes were at the first polar body
      (PB1) stage, those collected from retired females were immature upon collection
      but within 48 h 98.2+/-1.9% were cultured to the PB1 stage. The rate of ovulation
      was high in breeding females 5 days following stimulation but retired females
      were less reliable, and in both groups all oocytes were degraded. This is the
      first study to describe a reliable technique, involving ovarian stimulation
      during the intermediate phase and segregation of age groups, allowing the
      collection of a large number of healthy PB1 stage oocytes from S. crassicaudata.
      This is important for the development of further assisted reproductive techniques
      for this species and threatened dasyurids.

PMID- 19380427
TI  - Lipid peroxidation, assessed with BODIPY-C11, increases after cryopreservation of
      stallion spermatozoa, is stallion-dependent and is related to apoptotic-like
      changes.
AB  - Lipid peroxidation (LPO) of stallion spermatozoa was assessed in fresh semen and
      in samples of the same ejaculates after freezing and thawing. Particular
      attention was paid to individual differences in the susceptibility to LPO and its
      possible relationship with freezability. Innate levels of LPO were very low in
      fresh spermatozoa but increased after thawing, a change that was largely stallion
      dependent. The level of LPO in fresh spermatozoa was not correlated with that of
      the thawed spermatozoa. Negative correlations existed between LPO and intact
      membranes post-thaw (r=-0.789, P<0.001), and also between LPO and spermatozoa
      with high mitochondrial membrane potential (Deltapsim) post-thaw (r=-0.689,
      P<0.001). LPO was also highly and significantly correlated with caspase activity.
      The correlation between caspase activity in ethidium positive cells and LPO was
      r=0.772, P<0.001. This LPO is unlikely to represent, per se, a sign of
      cryopreservation-induced injury, but it is apparently capable of triggering
      'apoptotic-like changes' that could result in the sub-lethal cryodamage often
      seen among surviving spermatozoa.

PMID- 19380428
TI  - Implementation of a respiratory therapist-driven protocol for neonatal
      ventilation: impact on the premature population.
AB  - OBJECTIVE: The purpose of this work was to evaluate the impact of the
      implementation of a ventilation protocol driven by registered respiratory
      therapists on respiratory outcomes of premature infants with birth weight < or
      =1250 g. METHODS: A ventilation protocol driven by a registered respiratory
      therapist was developed by a multidisciplinary group and implemented in our unit
      in July 2004. A retrospective review of 301 inborn infants with birth weight < or
      =1250 g who were mechanically ventilated was performed. Ninety-three infants were
      ventilated before the ventilation protocol (before), 109 in the first year (after
      1) and 99 during the second year (after 2) after the ventilation protocol
      implementation. Data were collected with a predefined form. RESULTS: The baseline
      characteristics of the population were similar among the 3 groups, except for a
      significant smaller number of male infants in the first year after the protocol
      implementation. The significant differences among the 3 periods were as follows:
      (1) time of first extubation attempt; (2) duration of mechanical ventilation; and
      (3) rate of extubation failure (40%, 26%, and 20%). There was no difference in
      the rate of air leaks, patent ductus arteriosus ligation, necrotizing
      enterocolitis, bronchopulmonary dysplasia, or death. There was a significant
      decrease in the combined rates of intraventricular hemorrhage grades III to IV
      and/or periventricular leukomalacia (31%, 18%, and 4%) after the protocol
      implementation. CONCLUSIONS: In this study, we were able to demonstrate for the
      first time a significant improvement on the weaning time and duration of
      mechanical ventilation with the implementation of a ventilation protocol driven
      by a registered respiratory therapist in the premature population. Based on our
      experience, other institutions can customize ventilation protocols to their local
      practice. However, a prospective, randomized, controlled study should be planned
      to evaluate long-term outcomes such as BPD and neurodevelopment.

PMID- 19380429
TI  - Effects through 24 months of an HIV/AIDS prevention intervention program based on
      protection motivation theory among preadolescents in the Bahamas.
AB  - OBJECTIVES: The purpose of this work was to report the intervention effects of
      Focus on Youth in the Caribbean (youth HIV intervention), an HIV prevention
      intervention based on protection motivation theory, through 24 months of follow
      up on sexual risk and protection knowledge, perceptions, intentions, and behavior
      among Bahamian sixth-grade youth. METHODS: We randomly assigned 1360 sixth-grade
      youth (and their parents) attending 15 government elementary schools in the
      Bahamas to 1 of 3 conditions: (1) youth HIV intervention plus a parental
      monitoring/communication/HIV education intervention; (2) youth HIV intervention
      plus a parental goal-setting intervention; or (3) an environmental protection
      intervention plus the parental goal-setting intervention. Baseline and 4 follow
      up surveys at 6-month intervals were conducted. Intervention effects were
      assessed using the mixed model for continuous outcome variables and the
      generalized linear mixed model for dichotomous outcome variables. RESULTS:
      Through 24 months of follow-up, youth HIV intervention, in combination with the
      parent interventions, significantly increased youths' HIV/AIDS knowledge,
      perceptions of their ability to use condoms, perception of the effectiveness of
      condoms and abstinence, and condom use intention and significantly lowered
      perceived costs to remaining abstinent. There was a trend for higher condom use
      among youth in the Focus on Youth in the Caribbean groups at each follow-up
      interval. CONCLUSIONS: Focus on Youth in the Caribbean, in combination with 1 of
      2 parent interventions administered to preadolescents and their parents in the
      Bahamas, resulted in and sustained protective changes on HIV/AIDS knowledge,
      sexual perceptions, and condom use intention. Although rates of sexual experience
      remained low, the consistent trend at all of the follow-up periods for higher
      condom use among youth who received youth intervention reached marginal
      significance at 24 months. Additional follow-up is necessary to determine whether
      the apparent protective effect is statistically significant as more youth
      initiate sex and whether it endures over time.

PMID- 19380431
TI  - Tumor lysis syndrome in solid tumors.

PMID- 19380432
TI  - Is immunohistochemistry less sensitive than quantitative reverse transcriptase
      polymerase chain reaction for hormone receptor status determination in breast
      cancer?

PMID- 19380435
TI  - CA 19-9 and Lewis antigens in pancreatic cancer.

PMID- 19380436
TI  - Cancer is heterogeneous.

PMID- 19380437
TI  - Cheaper, faster, better: chasing the elusive clinical trial end point.

PMID- 19380438
TI  - Breast cancer classification: time for a change.

PMID- 19380439
TI  - Are we hitting the right combination for hormonally sensitive breast cancer?

PMID- 19380440
TI  - The Blood of the Lamb.

PMID- 19380441
TI  - Single nucleotide polymorphism at rs1982073:T869C of the TGFbeta 1 gene is
      associated with the risk of radiation pneumonitis in patients with non-small-cell
      lung cancer treated with definitive radiotherapy.
AB  - PURPOSE: In search of reliable biologic markers to predict the risk of normal
      tissue damage by radio(chemo)therapy before treatment, we investigated the
      association between single nucleotide polymorphisms (SNPs) in the transforming
      growth factor 1 (TGFbeta1) gene and risk of radiation pneumonitis (RP) in
      patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Using 164
      available genomic DNA samples from patients with NSCLC treated with definitive
      radio(chemo)therapy, we genotyped three SNPs of the TGFbeta1 gene (rs1800469:C
      509T, rs1800471:G915C, and rs1982073:T869C) by polymerase chain reaction
      restriction fragment length polymorphism method. We used Kaplan-Meier cumulative
      probability to assess the risk of grade > or = 3 RP and Cox proportional hazards
      analyses to evaluate the effect of TGFbeta1 genotypes on such risk. RESULTS:
      There were 90 men and 74 women in the study, with median age of 63 years.
      Radiation doses ranging from 60 to 70 Gy (median = 63 Gy) in 30 to 58 fractions
      were given to 158 patients (96.3%) and platinum-based chemotherapy to 147
      (89.6%). Grade > or = 2 and grade > or = 3 RP were observed in 74 (45.1%) and 36
      patients (22.0%), respectively. Multivariate analysis found CT/CC genotypes of
      TGFbeta1 rs1982073:T869C to be associated with a statistically significantly
      lower risk of RP grades > or = 2 (hazard ratio [HR] = 0.489; 95% CI, 0.227 to
      0.861; P = .013) and grades > or = 3 (HR = 0.390; 95% CI, 0.197 to .774; P =
      0.007), respectively, compared with the TT genotype, after adjustment for
      Karnofsky performance status, smoking status, pulmonary function, and dosimetric
      parameters. CONCLUSION: Our results showed that CT/CC genotypes of TGFbeta1
      rs1982073:T869C gene were associated with lower risk of RP in patients with NSCLC
      treated with definitive radio(chemo)therapy and thus may serve as a reliable
      predictor of RP.

PMID- 19380442
TI  - Primary care physicians' views of routine follow-up care of cancer survivors.
AB  - PURPOSE: Routine follow-up of adult cancer survivors is an important clinical and
      health service issue. Because of a lack of evidence supporting advantages of long
      term follow-up care in oncology clinics, there is increasing interest for the
      locus of this care to be provided by primary care physicians (PCPs). However,
      current Canadian PCP views on this issue have been largely unknown. METHODS: A
      mail survey of a random sample of PCPs across Canada, stratified by region and
      proximity to urban centers, was conducted. Views on routine follow-up of adult
      cancer survivors and modalities to facilitate PCPs in providing this care were
      determined. RESULTS: A total of 330 PCPs responded (adjusted response rate,
      51.7%). After completion of active treatment, PCPs were willing to assume
      exclusive responsibility for routine follow-up care after 2.4 +/- 2.3 years had
      elapsed for prostate cancer, 2.6 +/- 2.6 years for colorectal cancer, 2.8 +/- 2.5
      years for breast cancer, and 3.2 +/- 2.7 years for lymphoma. PCPs already
      providing this care were willing to provide exclusive care sooner. The most
      useful modalities PCPs felt would assist them in assuming exclusive
      responsibility for follow-up cancer care were (1) a patient-specific letter from
      the specialist, (2) printed guidelines, (3) expedited routes of rereferral, and
      (4) expedited access to investigations for suspected recurrence. CONCLUSION: With
      appropriate information and support in place, PCPs reported being willing to
      assume exclusive responsibility for the follow-up care of adult cancer survivors.
      Insights gained from this survey may ultimately help guide strategies in
      providing optimal care to these patients.

PMID- 19380443
TI  - Phase III noninferiority trial comparing irinotecan with oxaliplatin,
      fluorouracil, and leucovorin in patients with advanced colorectal carcinoma
      previously treated with fluorouracil: N9841.
AB  - PURPOSE: The primary goal of this multicenter phase III trial was to determine
      whether overall survival (OS) of fluorouracil (FU) -refractory patients was
      noninferior when treated with second-line infusional fluorouracil, leucovorin,
      and oxaliplatin (FOLFOX4; arm B) versus irinotecan (arm A). Cross-over to the
      other treatment on disease progression was mandated. PATIENTS AND METHODS:
      Patients who experienced treatment failure with one prior FU-based therapy and
      had not received prior irinotecan or oxaliplatin, either for metastatic disease
      or within 6 months of adjuvant FU therapy, were randomly assigned to arm A
      (irinotecan 350 or 300 mg/m(2) every 3 weeks) or arm B (FOLFOX4). RESULTS: A
      total of 491 patients were randomly assigned (arm A, n = 245; arm B, n = 246);
      288 (59%) had experienced treatment failure with FU for metastatic colorectal
      cancer. Two hundred twenty-seven patients (46%) received protocol-mandated third
      line therapy (arm A, 43%; arm B, 57%). Median survival was 13.8 months (95% CI,
      12.2 to 15.0 months) for initial treatment with FOLFOX4 and 14.3 months (95% CI,
      12.0 to 15.9 months) for irinotecan (P = .38; hazard ratio = 0.92; 95% CI, 0.8 to
      1.1). Response rates (RR; 28% v 15.5%; P = .0009) and time to progression (TTP;
      6.2 v 4.4 months; P = .0009) were significantly superior with FOLFOX4. In the
      nonrandom subset of patients who crossed over, RR and TTP improvements with
      FOLFOX4 continued into third-line treatment. Irinotecan therapy was associated
      with more grade 3 nausea, vomiting, diarrhea, and febrile neutropenia; FOLFOX4
      was associated with more neutropenia and paresthesias. CONCLUSION: In patients
      who experienced treatment failure with front-line FU therapy, OS does not
      significantly differ whether second-line therapy begins with irinotecan or
      FOLFOX4. FOLFOX4 produces higher RR and longer TTP. Both arms had notable OS in
      patients who experienced treatment failure with first-line FU therapy.

PMID- 19380445
TI  - Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP
      751,871 in combination with paclitaxel and carboplatin in previously untreated,
      locally advanced, or metastatic non-small-cell lung cancer.
AB  - PURPOSE: We conducted a phase II study of combination of the anti-insulin-like
      growth factor 1 receptor antibody CP-751,871 with paclitaxel and carboplatin
      (PCI) in advanced treatment-naive non-small-cell lung cancer (NSCLC). PATIENTS
      AND METHODS: Patients were randomly assigned (2:1) to paclitaxel 200 mg/m(2),
      carboplatin (area under the plasma concentration-time curve of 6), and CP-751,871
      10 to 20 mg/kg (PCI(10), PCI(20)) or paclitaxel and carboplatin alone (PC) every
      3 weeks for up to six cycles. PCI(10-20) patients could continue CP-751,871
      (figitumumab) treatment after chemotherapy discontinuation. Patients treated with
      PC experiencing disease progression were eligible to receive CP-751,871 at
      investigator's discretion. An additional nonrandomized single-arm cohort of 30
      patients with nonadenocarcinoma tumor histology receiving PCI(20) was enrolled on
      completion of the randomized study. RESULTS: A total of 156 patients were
      enrolled onto the randomized portion of the study. Safety and efficacy
      information are available for 151 patients (98 patients treated with PCI and 53
      patients treated with PC). Forty-eight patients treated with PCI received PCI(10)
      and 50 patients received PCI(20) in two sequential stages. Twenty of 53 patients
      treated with PC received CP-751,871 after disease progression. PCI was well
      tolerated. Fifty-four percent of patients treated with PCI and 42% of patients
      treated with PC had objective responses. Sixteen of 23 patients assessable for
      efficacy in the nonrandomized single-arm extension cohort also responded to
      treatment. Of note, 14 of 18 randomly assigned and 11 of 14 nonrandomly assigned
      patients treated with PCI with squamous cell carcinoma histology had response to
      treatment, including nine objective responses in bulky disease. Responses were
      also observed in two patients with squamous histology receiving CP-751,871 on PC
      discontinuation. PCI(20)/PC hazard ratio for progression-free survival was 0.8 to
      0.56, according to censorship. CONCLUSION: These data suggest that PCI(20) is
      safe and effective in patients with NSCLC.

PMID- 19380444
TI  - Prostate-specific antigen progression predicts overall survival in patients with
      metastatic prostate cancer: data from Southwest Oncology Group Trials 9346
      (Intergroup Study 0162) and 9916.
AB  - PURPOSE: Prostate-specific antigen progression (PSA-P) is an indicator of
      progression in hormone-sensitive (HS) and castration-resistant (CR) prostate
      cancer (PC). We evaluated different definitions of PSA-P as predictors of overall
      survival (OS). PATIENTS AND METHODS: A total of 1,078 patients with HSPC who were
      on hormones (Southwest Oncology Group [SWOG] trial 9346 [S9346]) and 597 patients
      with CRPC who were treated with chemotherapy (SWOG trial 9916 [S9916]) were
      eligible for this analysis. PSA-P definitions tested included the following: PSA
      Working Group, Prostate Cancer Working Group (PCWG 2008), and other definitions.
      A time-varying approach analyzed associations between PSA-P at any time and OS. A
      landmark analysis examined the relationship between PSA-P status at 7 months for
      S9346, or 3 months for S9916, and subsequent OS. RESULTS: In the time-varying
      analysis, both working groups definitions were strongly associated with OS (P <
      .001) in both study settings. In patients enrolled onto S9346, both definitions
      predicted a 2.4-fold increased risk of death (ROD) and a greater than four-fold
      increased ROD if PSA-P occurred in the first 7 months. In S9916, they predicted a
      40% increase in ROD and a two-fold increase in ROD if PSA-P occurred at 3 months.
      In landmark analyses of patients on S9346 by using the PCWG 2008 definition of
      PSA-P, median subsequent OS was 10 months versus 44 months in patients who did or
      did not have PSA-P by 7 months, respectively; in S9916, data were 11 months
      versus 18 months for patients who did or did not have PSA-P by 3 months,
      respectively. CONCLUSION: PSA-P, defined as an increase of > or = 25% greater
      than the nadir and an absolute increase of at least 2 or 5 ng/mL, predicts OS in
      HSPC and CRPC and may be a suitable end point for phase II studies in these
      settings.

PMID- 19380446
TI  - Oxidative stress, obesity, and breast cancer risk: results from the Shanghai
      Women's Health Study.
AB  - PURPOSE: Increased reactive oxygen species may exhaust the antioxidant capability
      of human defense systems, leading to oxidative stress and cancer development.
      Urinary F2-isoprostanes, secondary end products of lipid peroxidation, are more
      accurate markers of oxidative stress than other available biomarkers. No
      prospective study has investigated whether levels of 15-F(2t)-isoprostane (15
      F(2t)-IsoP) and its metabolite 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP (15-F(2t)
      IsoPM) are related to breast cancer risk. PATIENTS AND METHODS: We conducted a
      nested case-control study within the Shanghai Women's Health Study, a population
      based cohort study of 74,942 Chinese women between 40 and 70 years of age.
      Prediagnostic urinary 15-F(2t)-IsoP and 15-F(2t)-IsoPM were measured by gas
      chromatography mass spectrometry for 436 breast cancer cases and 852 individually
      matched controls. RESULTS: Urinary excretion of isoprostanes was not
      significantly different between cases and controls. However, among overweight
      women, levels of isoprostanes were positively associated with breast cancer risk,
      which became stronger with increasing body mass index (BMI). Among women with a
      BMI > or = 29, the odds ratio (OR) increased to 10.27 (95% CI, 2.41 to 43.80) for
      the highest compared with the lowest tertile of 15-F(2t)-IsoPM (P for trend =
      .003; P for interaction = .0004). In contrast, 15-F(2t)-IsoP and 15-F(2t)-IsoPM
      were inversely associated with breast cancer risk among nonoverweight women.
      Among women with a BMI < or = 23, breast cancer risk was reduced with increasing
      15-F(2t)-IsoP levels in a dose-response manner (P for trend = .006), with an OR
      of 0.46 (95% CI, 0.26 to 0.80) for the highest tertile versus the lowest (P for
      interaction = .006). CONCLUSION: Our results suggest that the role of oxidative
      stress in breast cancer development may depend on adiposity.

PMID- 19380447
TI  - Pooled analysis of individual patient-level data from all randomized, double
      blind, placebo-controlled trials of darbepoetin alfa in the treatment of patients
      with chemotherapy-induced anemia.
AB  - PURPOSE: Although numerous clinical trials have demonstrated the efficacy and
      tolerability of erythropoiesis-stimulating agents (ESAs) in patients with
      chemotherapy-induced anemia (CIA), results of some recent trials and one meta
      analysis have suggested that ESAs may negatively impact survival and/or disease
      control in patients with cancer. METHODS: To assess the benefits and risks of
      ESAs in CIA, we conducted a pooled analysis of individual patient-level data from
      all randomized, double-blind, placebo-controlled trials in 2,122 patients with
      CIA receiving darbepoetin alfa (DA; n = 1,200) or placebo (n = 912). RESULTS: DA
      did not increase mortality (hazard ratio = 0.97; 95% CI, 0.85 to 1.1) and had no
      effect on progression-free survival (hazard ratio = 0.93; 95% CI, 0.84 to 1.04)
      and disease progression (hazard ratio = 0.92; 95% CI, 0.82 to 1.03), but, as
      expected, increased the risk for thromboembolic events (hazard ratio = 1.57; 95%
      CI, 1.10 to 2.26). Overall and progression-free survival were not affected by
      baseline hemoglobin and seemed better in patients who achieved hemoglobin more
      than 12 or more than 13 g/dL. Transfusions and rates of hemoglobin increase (> 1
      g/dL in 14 days; > 2 g/dL in 28 days) owing to transfusions were associated with
      an increased risk for death and disease progression in both treatment groups; in
      the absence of transfusions, rates of hemoglobin increase did not appear to
      increase the risk for adverse outcomes. Compared with placebo, DA significantly
      reduced the risk of receiving one or more transfusion. CONCLUSION: There seemed
      to be no association between DA and risk of death or disease progression in this
      meta-analysis of individual patient data from DA studies conducted in CIA, the
      approved indication for ESAs in oncology.

PMID- 19380448
TI  - Progression-free survival as a predictor of overall survival in men with castrate
      resistant prostate cancer.
AB  - PURPOSE: To explore whether progression-free survival (PFS) or biochemical PFS
      can be used as a predictor of overall survival (OS) and to investigate the
      dependence between PFS and OS in men with castrate-resistant prostate cancer.
      PATIENTS AND METHODS: Data from nine Cancer and Leukemia Group B trials that
      enrolled 1,296 men from 1991 to 2004 were pooled. Men were eligible if they had
      prostate cancer that had progressed during androgen deprivation therapy and did
      not receive prior treatment with chemotherapy, immunotherapy, or other
      nonhormonal therapy. Landmark analyses of PFS at 3 and 6 months from
      randomization/registration were performed to minimize lead time bias. The
      proportional hazards model was used to assess the significance effect of PFS rate
      at 3 and at 6 months in predicting OS. In addition, biochemical progression using
      the definitions of Prostate-Specific Antigen Working Group (PSAW) Criteria PSAWG1
      and PSAWG2 were analyzed as time-dependent covariates in predicting OS. RESULTS:
      The median survival time among men who experienced progression at 3 months was
      9.2 months (95% CI, 8.0 to 10.0 months) compared with 17.8 months in men who did
      not experience progression at 3 months (95% CI, 16.2 to 20.4 months; P < .0001).
      Compared with men who did not progress at 3 and at 6 months, the adjusted hazard
      ratios for death were 2.0 (95% CI, 1.7 to 2.4; P < .001) and 1.9 (95% CI, 1.6 to
      2.4; P < .001) for men who experienced progression at 3 and 6 months,
      respectively. In addition, biochemical progression at 3 months predicted OS. The
      association between PFS and OS was 0.30 (95% confidence limits = 0.26, 0.32).
      CONCLUSION: PFS at 3 and 6 months and biochemical progression at 3 months predict
      OS. These observations require prospective validation.

PMID- 19380449
TI  - Phase II randomized study of neoadjuvant everolimus plus letrozole compared with
      placebo plus letrozole in patients with estrogen receptor-positive breast cancer.
AB  - PURPOSE: Cross-talk between the estrogen receptor (ER) and the phosphoinositide-3
      kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathways is a mechanism of
      resistance to endocrine therapy, and blockade of both pathways enhances antitumor
      activity in preclinical models. This study explored whether sensitivity to
      letrozole was enhanced with the oral mTOR inhibitor, everolimus (RAD001).
      PATIENTS AND METHODS: Two hundred seventy postmenopausal women with operable ER
      positive breast cancer were randomly assigned to receive 4 months of neoadjuvant
      treatment with letrozole (2.5 mg/day) and either everolimus (10 mg/day) or
      placebo. The primary end point was clinical response by palpation. Mandatory
      biopsies were obtained at baseline and after 2 weeks of treatment (ie, day 15).
      Samples were assessed for PI3K mutation status (PIK3CA) and for pharmacodynamic
      changes of Ki67, phospho-S6, cyclin D1, and progesterone receptor (PgR) by
      immunohistochemistry. RESULTS: Response rate by clinical palpation in the
      everolimus arm was higher than that with letrozole alone (ie, placebo; 68.1% v
      59.1%), which was statistically significant at the preplanned, one-sided, alpha =
      0.1 level (P = .062). Marked reductions in progesterone receptor and cyclin D1
      expression occurred in both treatment arms, and dramatic downregulation of
      phospho-S6 occurred only in the everolimus arm. An antiproliferative response, as
      defined by a reduction in Ki67 expression to natural logarithm of percentage
      positive Ki67 of less than 1 at day 15, occurred in 52 (57%) of 91 patients in
      the everolimus arm and in 25 (30%) of 82 patients in the placebo arm (P < .01).
      The safety profile was consistent with historical results of everolimus
      monotherapy; grades 3 to 4 adverse events occurred in 22.6% of patients who
      received everolimus and in 3.8% of patients who received placebo. CONCLUSION:
      Everolimus significantly increased letrozole efficacy in neoadjuvant therapy of
      patients with ER-positive breast cancer.

PMID- 19380450
TI  - [18F]fluorodeoxyglucose positron emission tomography correlates with Akt pathway
      activity but is not predictive of clinical outcome during mTOR inhibitor therapy.
AB  - PURPOSE: Positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG
      PET) has increasingly been used to evaluate the efficacy of anticancer agents. We
      investigated the role of FDG-PET as a predictive marker for response to mammalian
      target of rapamycin (mTOR) inhibition in advanced solid tumor patients and in
      murine xenograft models. PATIENTS AND METHODS: Thirty-four rapamycin-treated
      patients with assessable baseline and treatment FDG-PET and computed tomography
      scans were analyzed from two clinical trials. Clinical response was evaluated
      according to Response Evaluation Criteria in Solid Tumors, and FDG-PET response
      was evaluated by quantitative changes and European Organisation for Research and
      Treatment of Cancer (EORTC) criteria. Six murine xenograft tumor models were
      treated with temsirolimus. Small animal FDG-PET scans were performed at baseline
      and during treatment. The tumors were analyzed for the expression of pAkt and
      GLUT1. RESULTS: Fifty percent of patients with increased FDG-PET uptake and 46%
      with decreased uptake had progressive disease (PD). No objective response was
      observed. By EORTC criteria, the sensitivity of progressive metabolic disease on
      FDG-PET in predicting PD was 19%. Preclinical studies demonstrated similar
      findings, and FDG-PET response correlated with pAkt activation and plasma
      membrane GLUT1 expression. CONCLUSION: FDG-PET is not predictive of proliferative
      response to mTOR inhibitor therapy in both clinical and preclinical studies. Our
      findings suggest that mTOR inhibitors suppress the formation of mTORC2 complex,
      resulting in the inhibition of Akt and glycolysis independent of proliferation in
      a subset of tumors. Changes in FDG-PET may be a pharmacodynamic marker for Akt
      activation during mTOR inhibitor therapy. FDG-PET may be used to identify
      patients with persistent Akt activation following mTOR inhibitor therapy.

PMID- 19380451
TI  - Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone
      responsive postmenopausal patients with early breast cancer: the HOBOE trial.
AB  - PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant
      letrozole versus tamoxifen in postmenopausal patients with hormone-responsive
      early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS
      Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole
      plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone
      (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate
      (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12
      months of treatment. For each hormone, changes from baseline at 6 and 12 months
      were compared between treatment groups, and differences over time for each group
      were analyzed. Results Hormonal data were available for 139 postmenopausal
      patients with a median age of 62 years, with 43 patients assigned to tamoxifen
      and 96 patients assigned to letrozole alone or combined with zoledronic acid.
      Baseline values were similar between the two groups for all hormones. Many
      significant changes were observed between drugs and for each drug over time.
      Namely, three hormones seemed significantly affected by one drug only: estradiol
      that decreased and progesterone that increased with letrozole and cortisol that
      increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and
      slightly increasing with letrozole), LH (decreasing more with tamoxifen than with
      letrozole), testosterone (slightly increasing with letrozole but not enough to
      differ from tamoxifen), and DHEA-S (increasing with both drugs but not
      differently between them). Zoledronic acid did not have significant impact on
      hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in
      significantly distinct endocrine effects. Such differences can explain the higher
      efficacy of letrozole as compared with tamoxifen.

PMID- 19380452
TI  - Ki67 expression and docetaxel efficacy in patients with estrogen receptor
      positive breast cancer.
AB  - PURPOSE The indications of adjuvant chemotherapy for patients with estrogen
      receptor (ER) -positive breast cancer are controversial. We analyzed the
      predictive value of Ki67, HER2, and progesterone receptor (PR) expression for the
      efficacy of docetaxel in patients with ER-positive, node-positive breast cancer.
      PATIENTS AND METHODS Expression of Ki67, HER2, and PR was measured by
      immunohistochemistry in tumor samples from 798 patients with ER-positive breast
      cancer who participated in PACS01, a randomized trial that evaluated the efficacy
      of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age,
      tumor size, nodal involvement, treatment arm, and biomarkers. The predictive
      value of biomarkers was assessed by an interaction test. Disease-free survival
      (DFS) was the primary end point. Results Ki67, HER2, and PR were expressed in
      21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated
      with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive
      tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio
      for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were
      81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER
      positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with
      docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients
      with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with
      fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed
      between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P
      = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47
      to 1.66; P = .71). CONCLUSION Ki67 expression identifies a subset of patients
      with ER-positive breast cancer who could be sensitive to docetaxel treatment in
      the adjuvant setting.

PMID- 19380453
TI  - Prognostic factors in adult patients up to 60 years old with acute myeloid
      leukemia and translocations of chromosome band 11q23: individual patient data
      based meta-analysis of the German Acute Myeloid Leukemia Intergroup.
AB  - PURPOSE: To identify risk factors for induction success and overall survival (OS)
      and relapse-free survival (RFS) and to evaluate the impact of allogeneic stem
      cell transplantation (alloSCT) in adult patients up to 60 years old with acute
      myeloid leukemia (AML) and reciprocal translocations involving chromosome band
      11q23 [t(11q23)]. PATIENTS AND METHODS: An individual patient data-based meta
      analysis was performed on 180 adult patients with AML and t(11q23). These
      patients were identified by cytogenetics and/or molecular techniques and treated
      within eight prospective multicenter trials of the German AML Intergroup. The
      median follow-up time was 53 months. RESULTS: Complete remission rate was 71%.
      Favorable factors for induction success were the presence of a t(9;11), t(11q23)
      as a sole aberration, and de novo leukemia. OS rate at 4 years was 29%.
      Translocations other than t(9;11), platelets less than the median, secondary
      leukemia, and peripheral blasts greater than the median were adverse risk factors
      for OS. RFS rate at 4 years was 29%. The presence of a t(6;11) and peripheral
      blasts greater than the median had a negative impact on RFS. Three risk groups
      for OS and RFS could be defined by the combination of these factors with 4-year
      OS rates of 50%, 28%, and 5% and 4-year RFS rates of 37%, 26%, and 5%. An alloSCT
      from matched related or unrelated donors in first complete remission was
      beneficial, especially in t(6;11)-negative patients. CONCLUSION: Risk
      stratification of AML patients with reciprocal translocations of chromosome band
      11q23 is feasible based on the translocation partner and clinical parameters.

PMID- 19380454
TI  - Domestic homicide followed by parasuicide: a comparison with homicide and
      parasuicide.
AB  - Homicide-suicides are a rare yet very serious form of interpersonal violence that
      occur mainly in partnerships and families. As both perpetrator and victim die in
      a homicide- suicide, data sources in previous studies typically lack detailed
      information. This study overcomes this limitation by making use of homicides
      followed by a suicide attempt of the perpetrator (homicide-parasuicides). The
      authors examine to what extent these homicide-parasuicides can be understood as
      being primarily an expression of homicidal or of suicidal behavior. In total, 77
      homicide-parasuicides are compared to 430 homicides and 161 parasuicides. The
      results show that homicide-parasuicides constitute a different category of lethal
      violence with regard to demographic, individual, and event-related
      characteristics. Subanalyses of homicide-parasuicides involving women and
      children reveal similar differences. The finding that a large majority of the
      perpetrators were mentally ill, dependent on the victim, and killed when faced
      with separation from the victim may suggest that increased monitoring of this
      group might have preventive value.

PMID- 19380455
TI  - Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in
      type 2 diabetes and obesity.
AB  - OBJECTIVE: Osteoprotegerin (OPG) is a soluble tumour necrosis factor-receptor
      like molecule present in connective tissues, especially bone and vasculature. It
      is known to accumulate in the arterial wall in diabetes. As its synthesis in
      vascular cells is decreased by insulin, we wanted to elucidate the acute effects
      of insulin on plasma OPG concentrations in individuals with type 2 diabetes and
      obese individuals compared with lean controls. DESIGN: The study population
      consisted of ten type 2 diabetic, ten obese subjects, and ten lean subjects with
      no family history of diabetes. METHODS: All subjects underwent a 4-h euglycemic
      hyperinsulinemic clamp. Plasma OPG, insulin, lactate, HbA1c, cholesterol,
      triglycerides, free fatty acids (FFA), and glucose disposal rate were measured
      before and at the end of the clamp. RESULTS: Baseline OPG concentrations did not
      differ significantly between groups. Insulin infusion decreased plasma OPG
      concentrations in all groups (P<0.01); however, the fall in OPG was 50% less in
      obese and type 2 diabetic individuals (P=0.007). Baseline OPG correlated with
      fasting insulin, baseline lactate, and low density lipoprotein cholesterol in the
      diabetic group, and with baseline FFA in the lean group. The relative change of
      OPG in response to insulin correlated inversely with HbA1c and baseline FFA in
      the lean group. CONCLUSIONS: Acute hyperinsulinemia decreases plasma OPG, but
      with diminished effect in individuals with type 2 diabetes and obesity. Increased
      levels of OPG in arteries and plasma in diabetes together with the capability of
      plasma OPG as a cardiovascular risk predictor may be related to the described
      effects of insulin.

PMID- 19380457
TI  - Dietary modulation of ghrelin and leptin and gorging behavior after weight loss
      in the obese Zucker rat.
AB  - In this study, we measured ghrelin and leptin in obese Zucker rats after weight
      loss induced by calorie restriction using either a low-fat (LF) or high-energy
      palatable (HEPa) diet. After weight loss, the animals were refed lab chow and
      offered one hour-palatable test meals on the second and fifteenth days of
      refeeding. Both LF and HEPa rats lost 10% of their initial body weight
      (P<0.0001). Plasma ghrelin increased with calorie restriction in both groups
      (P<0.002) with a tendency to a higher increase in the HEPa group while plasma
      leptin decreased only in the LF group (P<0.01). Both groups ate the same quantity
      of chow during refeeding and both groups gorged on palatable diet during test
      meals at a very high constant intensity in HEPa rats. After one week of
      refeeding, ghrelin levels remained elevated in HEPa rats (+33.2%; P<0.001) while
      returning to baseline in LF rats. Plasma leptin remained low in LF rats. We
      conclude that weight loss on a palatable diet is possible if total energy intake
      is controlled. After stopping restriction, when a palatable diet is available,
      observed gorging might be dependent on specific ghrelin and leptin changes.

PMID- 19380456
TI  - The chicken type III GnRH receptor homologue is predominantly expressed in the
      pituitary, and exhibits similar ligand selectivity to the type I receptor.
AB  - Two GnRH isoforms (cGnRH-I and GnRH-II) and two GnRH receptor subtypes (cGnRH-R-I
      and cGnRH-R-III) occur in chickens. Differential roles for these molecules in
      regulating gonadotrophin secretion or other functions are unclear. To investigate
      this we cloned cGnRH-R-III from a broiler chicken and compared its structure,
      expression and pharmacological properties with cGnRH-R-I. The broiler cGnRH-R-III
      cDNA was 100% identical to the sequence reported in the red jungle fowl and white
      leghorn breed. Pituitary cGnRH-R-III mRNA was approximately 1400-fold more
      abundant than cGnRH-R-I mRNA. Northern analysis indicated a single cGnRH-R-III
      transcript. A pronounced sex and age difference existed, with higher pituitary
      transcript levels in sexually mature females versus juvenile females. In
      contrast, higher expression levels occurred in juvenile males versus sexually
      mature males. Functional studies in COS-7 cells indicated that cGnRH-R-III has a
      higher binding affinity for GnRH-II than cGnRH-I (K(d): 0.57 vs 19.8 nM) with
      more potent stimulation of inositol phosphate production (ED(50): 0.8 vs 4.38
      nM). Similar results were found for cGnRH-R-I, (K(d): 0.51 vs 10.8 nM) and
      (ED(50): 0.7 vs 2.8 nM). The initial rate of internalisation was faster for cGnRH
      R-III than cGnRH-R-I (26 vs 15.8%/min). Effects of GnRH antagonists were compared
      at the two receptors. Antagonist #27 distinguished between cGnRH-R-I and cGnRH-R
      III (IC(50): 2.3 vs 351 nM). These results suggest that cGnRH-R-III is probably
      the major mediator of pituitary gonadotroph function, that antagonist #27 may
      allow delineation of receptor subtype function in vitro and in vivo and that
      tissue-specific recruitment of cGnRH-R isoforms has occurred during evolution.

PMID- 19380458
TI  - 17Beta-estradiol inhibits 11beta-hydroxysteroid dehydrogenase type 1 activity in
      rodent adipocytes.
AB  - 17Beta-estradiol (E(2)) serves as an anti-obesity steroid; however, the mechanism
      underlying this effect has not been fully clarified. The effect of E(2) on
      adipocytes opposes that of glucocorticoids, which potentiate adipogenesis and
      anabolic lipid metabolism. The key to the intracellular activation of
      glucocorticoid in adipocytes is 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1), which catalyses the production of active glucocorticoids (cortisol
      in humans and corticosterone in rodents) from inactive 11-keto steroids
      (cortisone in humans and 11-dehydrocorticosterone in rodents). Using
      differentiated 3T3-L1 adipocytes, we showed that E(2) inhibited 11beta-HSD1
      activity. Estrogen receptor (ER) antagonists, ICI-182 780 and tamoxifen, failed
      to reverse this inhibition. A significant inhibitory effect of E(2) on 11beta
      HSD1 activity was observed within 5-10 min. Furthermore, acetylation or alpha
      epimerization of 17-hydroxy group of E(2) attenuated the inhibitory effect on
      11beta-HSD1. These results indicate that the inhibition of 11beta-HSD1 by E(2)
      depends on neither an ER-dependent route, transcriptional pathway nor non
      specific fashion. Hexose-6-phosphate dehydrogenase, which provides the cofactor
      NADPH for full activation of 11beta-HSD1, was unaffected by E(2). A kinetic study
      revealed that E(2) acted as a non-competitive inhibitor of 11beta-HSD1. The
      inhibitory effect of E(2) on 11beta-HSD1 was reproduced in adipocytes isolated
      from rat mesenteric fat depots. This is the first demonstration that E(2)
      inhibits 11beta-HSD1, thereby providing a novel insight into the anti-obesity
      mechanism of estrogen.

PMID- 19380459
TI  - Thyroid hormone regulation of mRNAs encoding thyrotropin beta-subunit,
      glycoprotein alpha-subunit, and thyroid hormone receptors alpha and beta in
      brain, pituitary gland, liver, and gonads of an adult teleost, Pimephales
      promelas.
AB  - Thyroid hormones (THs) regulate growth, morphological development, and migratory
      behaviors in teleost fish, yet little is known about the transcriptional dynamics
      of gene targets for THs in these taxa. Here, we characterized TH regulation of
      mRNAs encoding thyrotropin subunits and thyroid hormone receptors (TRs) in an
      adult teleost fish model, the fathead minnow (Pimephales promelas). Breeding
      pairs of adult minnows were fed diets containing 3,5,3'-triiodo-L-thyronine
      (T(3)) or the goitrogen methimazole for 10 days. In males and females, dietary
      intake of exogenous T(3) elevated circulating total T(3), while methimazole
      depressed plasma levels of total thyroxine (T(4)). In both sexes, this
      methimazole-induced reduction in T(4) led to elevated mRNA abundance for
      thyrotropin beta-subunit (tshbeta) in the pituitary gland. Fish treated with T(3)
      had elevated transcript levels for TR isoforms alpha and beta (tralpha and
      trbeta) in the liver and brain, but reduced levels of brain mRNA for the
      immediate-early gene basic transcription factor-binding protein (bteb). In the
      ovary and testis, exogenous T(3) elevated gene transcripts for tshbeta,
      glycoprotein hormone alpha-subunit (gphalpha), and trbeta, while not affecting
      tralpha levels. Taken together, these results demonstrate negative feedback of
      T(4) on pituitary tshbeta, identify tralpha and trbeta as T(3)-autoinduced genes
      in the brain and liver, and provide new evidence that tshbeta, gphalpha, and
      trbeta are THs regulated in the gonad of teleosts. Adult teleost models are
      increasingly used to evaluate the endocrine-disrupting effects of chemical
      contaminants, and our results provide a systemic assessment of TH-responsive
      genes during that life stage.

PMID- 19380460
TI  - Chromatin analysis of occluded genes.
AB  - We recently described two opposing states of transcriptional competency. One is
      termed 'competent' whereby a gene is capable of responding to trans-acting
      transcription factors of the cell, such that it is active if appropriate
      transcriptional activators are present, though it can also be silent if
      activators are absent or repressors are present. The other is termed 'occluded'
      whereby a gene is silenced by cis-acting, chromatin-based mechanisms in a manner
      that blocks it from responding to trans-acting factors, such that it is silent
      even when activators are present in the cellular milieu. We proposed that gene
      occlusion is a mechanism by which differentiated cells stably maintain their
      phenotypic identities. Here, we describe chromatin analysis of occluded genes. We
      found that DNA methylation plays a causal role in maintaining occlusion for a
      subset of occluded genes. We further examined a variety of other chromatin marks
      typically associated with transcriptional silencing, including histone variants,
      covalent histone modifications and chromatin-associated proteins. Surprisingly,
      we found that although many of these marks are robustly linked to silent genes
      (which include both occluded genes and genes that are competent but silent), none
      is linked specifically to occluded genes. Although the observation does not rule
      out a possible causal role of these chromatin marks in occlusion, it does suggest
      that these marks might be secondary effect rather than primary cause of the
      silent state in many genes.

PMID- 19380461
TI  - Pneumorrhachis and pneumocephalus due to a sacral pressure sore after paraplegia.

PMID- 19380462
TI  - Accurate estimation of gene evolutionary rates using XRATE, with an application
      to transmembrane proteins.
AB  - XRATE implements algorithms for comparative annotation, ancestral reconstruction,
      evolutionary rate estimation, and simulation. Its modeling repertoire includes
      phylogenetic stochastic context-free grammars and phylo-hidden Markov models.
      Following earlier tests of XRATE as a machine-learning tool suitable for
      alignment annotation, we now report the first tests of XRATE as a precise
      quantitative instrument for estimating evolutionary rates. We implement a codon
      model similar to that of Goldman and Yang (1994) (A codon-based model of
      nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 11: 725
      736) and show that XRATE's parameter estimates are consistent with those of PAML.
      To demonstrate its utility, we apply the model to measure the difference in
      selective strength (omega) between intracellular and secreted regions of type I
      transmembrane proteins. In 215 of 303 instances, a complex model with individual
      omega for each region provides a better fit to the data than the simpler single
      omega value model. Secreted portions of type I transmembrane proteins show an
      elevation in omega similar to that seen for secreted protein genes. Less
      stringent purifying selection is thus a general property of the extracellular
      milieu, rather than being specific to only soluble and secreted proteins.

PMID- 19380463
TI  - Evolution of ultrasmall spliceosomal introns in highly reduced nuclear genomes.
AB  - Intron reduction and loss is a significant component of genome compaction in many
      eukaryotic lineages, including yeasts, microsporidia, and some nucleomorphs.
      Nucleomorphs are the extremely reduced relicts of algal endosymbiont nuclei found
      in two lineages, cryptomonads and chlorarachniophytes. In cryptomonads, introns
      are rare or even lost altogether. In contrast, the nucleomorph of the
      chlorarachniophyte Bigelowiella natans contains the smallest nuclear genome known
      but paradoxically also retained over 800 tiny spliceosomal introns, ranging from
      18 to 21 nt in length. Because introns have not been described in any other
      chlorarachniophyte nucleomorph, we do not know when these introns were reduced or
      whether they have been lost in other lineages. To gain insight into the evolution
      of these unique introns, we sequenced more than 150 spliceosomal introns in the
      nucleomorph of the chlorarachniophyte Gymnochlora stellata and compared size
      distribution, sequence features, and patterns of gain/loss. To clarify the
      possible relationship between intron size and splicing efficiency, we also
      analyzed the outcome of 580 splicing events. Overall, these data indicate that
      the radical intron size reduction took place in the ancestor of all extant
      chlorarachniophytes and that although most introns have been retained through
      this reductive process, intron loss has also occurred. We also show that intron
      size is not static, and splicing is not determined strictly by size, but that
      size does play a strong role in splicing efficiency, likely as part of a
      combination of sequence features and size.

PMID- 19380464
TI  - Holistic nurses' examinations: past, present, future.
AB  - Social and professional paradigm shifts of the 1990s moved holistic nursing into
      the mainstream of health care, resulting in the need for national certification
      of Holistic Nurses. Given the assumptions that certification examinations are
      based on the knowledge, skills, and abilities prerequisite for competent practice
      in a given specialty, and that the certification credential tells the public and
      peers that the certificant has such knowledge, The American Holistic Nurses
      Association's Leadership Council (AHNA-LC) initiated certification processes in
      1994. On the request of AHNA-LC, the American Holistic Nurses' Certification
      Corporation (AHNCC) assumed these responsibilities in April, 1997. Since then,
      AHNCC has overseen the revision of the first certification process for holistic
      nursing prepared at the baccalaureate level and development of a second one
      designed for holistic nurses prepared in graduate nursing programs. This article
      describe these developmental processes.

PMID- 19380465
TI  - Prolonged impact of antibiotics on intestinal microbial ecology and
      susceptibility to enteric Salmonella infection.
AB  - The impact of antibiotics on the host's protective microbiota and the resulting
      increased susceptibility to mucosal infection are poorly understood. In this
      study, antibiotic regimens commonly applied to murine enteritis models are used
      to examine the impact of antibiotics on the intestinal microbiota, the time
      course of recovery of the biota, and the resulting susceptibility to enteric
      Salmonella infection. Molecular analysis of the microbiota showed that antibiotic
      treatment has an impact on the colonization of the murine gut that is site and
      antibiotic dependent. While combinations of antibiotics were able to eliminate
      culturable bacteria, none of the antibiotic treatments were effective at
      sterilizing the intestinal tract. Recovery of total bacterial numbers occurs
      within 1 week after antibiotic withdrawal, but alterations in specific bacterial
      groups persist for several weeks. Increased Salmonella translocation associated
      with antibiotic pretreatment corrects rapidly in association with the recovery of
      the most dominant bacterial group, which parallels the recovery of total
      bacterial numbers. However, susceptibility to intestinal colonization and mucosal
      inflammation persists when mice are infected several weeks after withdrawal of
      antibiotics, correlating with subtle alterations in the intestinal microbiome
      involving alterations of specific bacterial groups. These results show that the
      colonizing microbiotas are integral to mucosal host protection, that specific
      features of the microbiome impact different aspects of enteric Salmonella
      pathogenesis, and that antibiotics can have prolonged deleterious effects on
      intestinal colonization resistance.

PMID- 19380466
TI  - Novel subtilase cytotoxin produced by Shiga-toxigenic Escherichia coli induces
      apoptosis in vero cells via mitochondrial membrane damage.
AB  - Subtilase cytotoxin (SubAB) is an AB(5) cytotoxin produced by some strains of
      Shiga-toxigenic Escherichia coli. The A subunit is a subtilase-like serine
      protease and cleaves an endoplasmic reticulum chaperone, BiP, leading to
      transient inhibition of protein synthesis and cell cycle arrest at G(1) phase.
      Here we show that SubAB, but not the catalytically inactive mutant SubAB(S272A),
      induced apoptosis in Vero cells, as detected by DNA fragmentation and annexin V
      binding. SubAB induced activation of caspase-3, -7, and -8. Caspase-3 appeared
      earlier than caspase-8, and by use of specific caspase inhibitors, it was
      determined that caspase-3 may be upstream of caspase-8. A general caspase
      inhibitor blocked SubAB-induced apoptosis, detected by annexin V binding. SubAB
      also stimulated cytochrome c release from mitochondria, which was not suppressed
      by caspase inhibitors. In HeLa cells, Apaf-1 small interfering RNA inhibited
      caspase-3 activation, suggesting that cytochrome c might form an apoptosome,
      leading to activation of caspase-3. These data suggested that SubAB induced
      caspase-dependent apoptosis in Vero cells through mitochondrial membrane damage.

PMID- 19380467
TI  - The K5 capsule of Escherichia coli strain Nissle 1917 is important in mediating
      interactions with intestinal epithelial cells and chemokine induction.
AB  - Escherichia coli strain Nissle 1917 has been widely used as a probiotic for the
      treatment of inflammatory bowel disorders and shown to have immunomodulatory
      effects. Nissle 1917 expresses a K5 capsule, the expression of which often is
      associated with extraintestinal and urinary tract isolates of E. coli. In this
      paper, we investigate the role of the K5 capsule in mediating interactions
      between Nissle 1917 and intestinal epithelial cells. We show that the loss of
      capsule significantly reduced the level of monocyte chemoattractant protein 1
      (MCP-1), RANTES, macrophage inflammatory protein 2alpha (MIP-2alpha), MIP-2beta,
      interleukin-8, and gamma interferon-inducible protein 10 induction by Nissle 1917
      in both Caco-2 cells and MCP-1 induction in ex vivo mouse small intestine. The
      complementation of the capsule-minus mutation confirmed that the effects on
      chemokine induction were capsule specific. The addition of purified K5, but not
      K1, capsular polysaccharide to the capsule-minus Nissle 1917 at least in part
      restored chemokine induction to wild-type levels. The purified K5 capsular
      polysaccharide alone was unable to stimulate chemokine production, indicating
      that the K5 polysaccharide was acting to mediate interactions between Nissle 1917
      and intestinal epithelial cells. The induction of chemokine by Nissle 1917 was
      generated predominantly by interaction with the basolateral surface of Caco-2
      cells, suggesting that Nissle 1917 will be most effective in inducing chemokine
      expression where the epithelial barrier is disrupted.

PMID- 19380468
TI  - Cellular tumor necrosis factor, gamma interferon, and interleukin-6 responses as
      correlates of immunity and risk of clinical Plasmodium falciparum malaria in
      children from Papua New Guinea.
AB  - The role of early to intermediate Plasmodium falciparum-induced cellular
      responses in the development of clinical immunity to malaria is not well
      understood, and such responses have been proposed to contribute to both immunity
      and risk of clinical malaria episodes. To investigate whether P. falciparum
      induced cellular responses are able to function as predictive correlates of
      parasitological and clinical outcomes, we conducted a prospective cohort study of
      children (5 to 14 years of age) residing in a region of Papua New Guinea where
      malaria is endemic Live, intact P. falciparum-infected red blood cells were
      applied to isolated peripheral blood mononuclear cells obtained at baseline.
      Cellular cytokine production, including production of interleukin-2 (IL-2), IL-4,
      IL-6, IL-10, tumor necrosis factor (TNF) (formerly tumor necrosis factor alpha),
      and gamma interferon (IFN-gamma), was measured, and the cellular source of key
      cytokines was investigated. Multicytokine models revealed that increasing P.
      falciparum-induced IL-6 production was associated with an increased incidence of
      P. falciparum clinical episodes (incidence rate ratio [IRR], 1.75; 95% confidence
      interval [CI], 1.20 to 2.53), while increasing P. falciparum-induced TNF and IFN
      gamma production was associated with a reduced incidence of clinical episodes
      (IRR for TNF, 0.55 [95% CI, 0.38 to 0.80]; IRR for IFN-gamma, 0.71 [95% CI, 0.55
      to 0.90]). Furthermore, we found that monocytes/macrophages and gammadelta-T
      cells are important for the P. falciparum-induced production of IL-6 and TNF.
      Early to intermediate cellular cytokine responses to P. falciparum may therefore
      be important correlates of immunity and risk of symptomatic malaria episodes and
      thus warrant detailed investigation in relation to the development and
      implementation of effective vaccines.

PMID- 19380469
TI  - Processing of Pseudomonas aeruginosa exotoxin A is dispensable for cell
      intoxication.
AB  - Exotoxin A is a major virulence factor of Pseudomonas aeruginosa. This toxin
      binds to a specific receptor on animal cells, allowing endocytosis of the toxin.
      Once in endosomes, the exotoxin can be processed by furin to generate a C
      terminal toxin fragment that lacks the receptor binding domain and is
      retrogradely transported to the endoplasmic reticulum for retrotranslocation to
      the cytosol through the Sec61 channel. The toxin then blocks protein synthesis by
      ADP ribosylation of elongation factor 2, thereby triggering cell death. A shorter
      intracellular route has also been described for this toxin. It involves direct
      translocation of the entire toxin from endosomes to the cytosol and therefore
      does not rely on furin-mediated cleavage. To examine the implications of
      endosomal translocation in the intoxication process, we investigated whether the
      toxin required furin-mediated processing in order to kill cells. We used three
      different approaches. We first fused to the N terminus of the toxin proteins with
      different unfolding abilities so that they inhibited or did not inhibit endosomal
      translocation of the chimera. We then assayed the amount of toxin fragments
      delivered to the cytosol during cell intoxication. Finally we used furin
      inhibitors and examined the fate and intracellular localization of the toxin and
      its receptor. The results showed that exotoxin cytotoxicity results largely from
      endosomal translocation of the entire toxin. We found that the C-terminal
      fragment was unstable in the cytosol.

PMID- 19380470
TI  - Glucose and glycolysis are required for the successful infection of macrophages
      and mice by Salmonella enterica serovar typhimurium.
AB  - Salmonella is a widespread zoonotic enteropathogen that causes gastroenteritis
      and fatal typhoidal disease in mammals. During systemic infection of mice,
      Salmonella enterica serovar Typhimurium resides and replicates in macrophages
      within the "Salmonella-containing vacuole" (SCV). It is surprising that the
      substrates and metabolic pathways necessary for growth of S. Typhimurium within
      the SCV of macrophages have not been identified yet. To determine whether S.
      Typhimurium utilized sugars within the SCV, we constructed a series of S.
      Typhimurium mutants that lacked genes involved in sugar transport and catabolism
      and tested them for replication in mice and macrophages. These mutants included a
      mutant with a mutation in the pfkAB-encoded phosphofructokinase, which catalyzes
      a key committing step in glycolysis. We discovered that a pfkAB mutant is
      severely attenuated for replication and survival within RAW 264.7 macrophages. We
      also show that disruption of the phosphoenolpyruvate:carbohydrate
      phosphotransferase system by deletion of the ptsHI and crr genes reduces S.
      Typhimurium replication within RAW 264.7 macrophages. We discovered that mutants
      unable to catabolize glucose due to deletion of ptsHI, crr, and glk or deletion
      of ptsG, manXYZ, and glk showed reduced replication within RAW 264.7 macrophages.
      This study proves that S. Typhimurium requires glycolysis for infection of mice
      and macrophages and that transport of glucose is required for replication within
      macrophages.

PMID- 19380471
TI  - The Staphylococcus aureus GGDEF domain-containing protein, GdpS, influences
      protein A gene expression in a cyclic diguanylic acid-independent manner.
AB  - Staphylococcus aureus is an important human pathogen that is the principal cause
      of a variety of diseases, ranging from localized skin infections to life
      threatening systemic infections. The success of the organism as a pathogen and
      its ability to cause such a wide range of infections are due to its extensive
      virulence factors. In this study, we identified the role of the only GGDEF domain
      protein (GdpS [GGDEF domain protein from Staphylococcus]) in the virulence of S.
      aureus NCTC8325. Inactivation of gdpS results in an alteration in the production
      of a range of virulence factors, such as serine and cysteine proteases,
      fibrinogen-binding proteins, and, specifically, protein A (Spa), a major surface
      protein of S. aureus. The transcript level of spa decreases eightfold in the gdpS
      mutant compared with the parental NCTC8325 strain. Furthermore, the transcript
      level of sarS, which encodes a direct positive regulator of spa, also decreases
      in the gdpS mutant compared with the wild type, while the transcript levels of
      agr, sarA, sarT, and rot display no apparent changes in the gdpS mutant,
      suggesting that GdpS affects the expression of spa through interaction with SarS
      by unknown mechanisms. Furthermore, the complementation assays show that the
      influences of GdpS on spa and sarS depend on its N-terminal domain, which is
      predicted to be the sensor of a two-component system, rather than its C-terminal
      GGDEF domain with conserved GGDEF, suggesting that GdpS functions in S. aureus by
      an unknown mechanism independent of 3',5'-cyclic diguanylic acid signaling.

PMID- 19380472
TI  - Glyceraldehyde-3-phosphate dehydrogenase is a surface-associated, fibronectin
      binding protein of Trichomonas vaginalis.
AB  - Trichomonas vaginalis colonizes the urogenital tract of humans and causes
      trichomonosis, the most prevalent nonviral sexually transmitted disease. We have
      shown an association of T. vaginalis with basement membrane extracellular matrix
      components, a property which we hypothesize is important for colonization and
      persistence. In this study, we identify a fibronectin (FN)-binding protein of T.
      vaginalis. A monoclonal antibody (MAb) from a library of hybridomas that
      inhibited the binding of T. vaginalis organisms to immobilized FN was identified.
      The MAb (called ws1) recognized a 39-kDa protein and was used to screen a cDNA
      expression library of T. vaginalis. A 1,086-bp reactive cDNA clone that encoded a
      protein of 362 amino acids with identity to glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) was obtained. The gapdh gene was cloned, and recombinant
      GAPDH (rGAPDH) was expressed in Escherichia coli cells. Natural GAPDH and rGAPDH
      bound to immobilized FN and to plasminogen and collagen but not to laminin. MAb
      ws1 inhibited binding to FN. GAPDH was detected on the surface of trichomonads
      and was upregulated in synthesis and surface expression by iron. Higher levels of
      binding to FN were seen for organisms grown in iron-replete medium than for
      organisms grown in iron-depleted medium. In addition, decreased synthesis of
      GAPDH by antisense transfection of T. vaginalis gave lower levels of organisms
      bound to FN and had no adverse effect on growth kinetics. Finally, GAPDH did not
      associate with immortalized vaginal epithelial cells (VECs), and neither GAPDH
      nor MAb ws1 inhibited the adherence of trichomonads to VECs. These results
      indicate that GAPDH is a surface-associated protein of T. vaginalis with
      alternative functions.

PMID- 19380473
TI  - The arginine catabolic mobile element is not associated with enhanced virulence
      in experimental invasive disease caused by the community-associated methicillin
      resistant Staphylococcus aureus USA300 genetic background.
AB  - USA300 has become the predominant community-associated methicillin (meticillin)
      resistant Staphylococcus aureus (CA-MRSA) genetic background in most U.S.
      communities. The reasons for the dominance of this genetic background are
      unclear, but the presence of the recently identified arginine catabolic mobile
      element (ACME) in the USA300 genome has been advocated as one possibility. CA
      MRSA clinical isolates (USA300) differing in the presence or absence of ACME and
      a USA300 wild-type/ACME deletion mutant pair were analyzed for in vitro
      expression of global regulatory genes and production of virulence factors. The
      virulence of these isolates was compared in rodent models of necrotizing
      pneumonia and skin infection. There was no significant difference in the
      expression of selected genes mediating virulence (hla, lukSF-PV, agr, saeRS)
      among the isolates tested, regardless of the presence of ACME. There was a higher
      abundance of alpha-hemolysin in culture supernatants among ACME-positive isolates
      than among ACME-negative isolates, but there was no significant difference in the
      levels of protein A. The presence of ACME was not associated with increased
      virulence in a rat model of necrotizing pneumonia, as assessed by mortality, in
      vivo bacterial survival, and severity of lung pathology. Nor was the presence of
      ACME associated with increased dermonecrosis in a model of skin infection. We
      conclude that ACME is not necessary for virulence in rodent models of CA-MRSA
      USA300 pneumonia or skin infection.

PMID- 19380474
TI  - Shiga toxin 2 is specifically released from bacterial cells by two different
      mechanisms.
AB  - Shiga toxin 1 (Stx1) is located in the periplasmic fraction, while Stx2 is found
      in the extracellular fraction, suggesting that enterohemorrhagic Escherichia coli
      (EHEC) contains a specific Stx2 release system. Both stx(1) and stx(2) are found
      within the late operons of Stx-encoding phages. Stx2 production is greatly
      induced by mitomycin C, suggesting that stx(2) can transcribe from the late phage
      promoter of the Stx2-encoding phage. However, the Stx1 promoter adjacent to
      stx(1) is a dominant regulatory element in Stx1 production. With the deletion of
      phage lysis genes of the Stx2-encoding phage, Stx2 remains in the bacterial
      cells. Further, we demonstrate that the Stx2-encoding phage, but not the Stx1
      encoding phage, is spontaneously induced at extremely low rates. These results
      indicate that spontaneously specific Stx2-encoding phage induction is involved in
      specific Stx2 release from bacterial cells. Furthermore, to examine whether
      another system for specific Stx2 release is present in EHEC, we analyze the stx
      replaced mutants. As expected, Stx2 derived from the Stx1 promoter is located in
      both the extracellular and cell-associated fractions, while mutant Stx2 (B
      subunit, S31N) derived from the Stx1 promoter is found only in the cell
      associated fraction. These results indicate that EHEC has another Stx2 release
      system that strictly recognizes the serine 31 residue of the B subunit. Overall,
      we present evidence that specific Stx2 release from bacterial cells is involved
      in both the Stx2-encoding phage induction system and another Stx2 release system.

PMID- 19380475
TI  - Anti-alpha-hemolysin monoclonal antibodies mediate protection against
      Staphylococcus aureus pneumonia.
AB  - Staphylococcus aureus pneumonia is one of the most common invasive diseases
      caused by this human pathogen. S. aureus alpha-hemolysin, a pore-forming
      cytotoxin, is an essential virulence factor in the pathogenesis of pneumonia.
      Vaccine-based targeting of this toxin provides protection against lethal
      staphylococcal pneumonia in a murine model system, suggesting that a monoclonal
      antibody-based therapy may likewise prove to be efficacious for prevention and
      treatment of this disease. We report the generation of two distinct anti-alpha
      hemolysin monoclonal antibodies that antagonize toxin activity, preventing human
      lung cell injury in vitro and protecting experimental animals against lethal S.
      aureus pneumonia. Each of these two monoclonal antibodies recognized an epitope
      within the first 50 amino acid residues of the mature toxin and blocked the
      formation of a stable alpha-hemolysin oligomer on the target cell surface. Active
      immunization with the first 50 amino acids of the toxin also conferred protection
      against S. aureus pneumonia. Together, these data reveal passive and active
      immunization strategies for prevention or therapy of staphylococcal pneumonia and
      highlight the potential role that a critical epitope may play in defining human
      susceptibility to this deadly disease.

PMID- 19380476
TI  - M-cell targeting of whole killed bacteria induces protective immunity against
      gastrointestinal pathogens.
AB  - As the majority of human pathogens infect via a mucosal surface, delivery of
      killed vaccines by mucosal routes could potentially improve protection against
      many such organisms. Our ability to develop effective killed mucosal vaccines is
      inhibited by a lack of adjuvants that are safe and effective in humans. The Ulex
      europaeus agglutinin I (UEA-I) lectin specifically binds M cells lining the
      murine gastrointestinal tract. We explored the potential for M-cell-targeted
      vaccination of whole, killed Helicobacter pylori, the main causative agent of
      peptic ulcer disease and gastric cancer, and Campylobacter jejuni, the most
      common cause of diarrhea. Oral delivery of UEA-I-agglutinated H. pylori or C.
      jejuni induced a significant increase in both serum and intestinal antibody
      levels. This elevated response (i) required the use of whole bacteria, as it did
      not occur with lysate; (ii) was not mediated by formation of particulate clumps,
      as agglutination with a lectin with a different glycan specificity had no effect;
      and (iii) was not due to lectin-mediated, nonspecific immunostimulatory activity,
      as UEA-I codelivery with nonagglutinated bacteria did not enhance the response.
      Vaccination with UEA-I-agglutinated, killed whole H. pylori induced a protective
      response against subsequent live challenge that was as effective as that induced
      by cholera toxin adjuvant. Moreover, vaccination against C. jejuni by this
      approach resulted in complete protection against challenge in almost all animals.
      We believe that this is the first demonstration that targeting of whole killed
      bacteria to mucosal M cells can induce protective immunity without the addition
      of an immunostimulatory adjuvant.

PMID- 19380477
TI  - Retraction: Cheng B-Q, et al. Chemoembolization combined with radiofrequency
      ablation for patients with hepatocellular carcinoma larger than 3 cm: a
      randomized controlled trial. JAMA. 2008;299(14):1669-1677.

PMID- 19380478
TI  - A genetic screen for suppressors of a mutated 5' splice site identifies factors
      associated with later steps of spliceosome assembly.
AB  - Many alleles of human disease genes have mutations within splicing consensus
      sequences that activate cryptic splice sites. In Caenorhabditis elegans, the unc
      73(e936) allele has a G-to-U mutation at the first base of the intron downstream
      of exon 15, which results in an uncoordinated phenotype. This mutation triggers
      cryptic splicing at the -1 and +23 positions and retains some residual splicing
      at the mutated wild-type (wt) position. We previously demonstrated that a
      mutation in sup-39, a U1 snRNA gene, suppresses e936 by increasing splicing at
      the wt splice site. We report here the results of a suppressor screen in which we
      identify three proteins that function in cryptic splice site choice. Loss-of
      function mutations in the nonessential splicing factor smu-2 suppress e936
      uncoordination through changes in splicing. SMU-2 binds SMU-1, and smu-1(RNAi)
      also leads to suppression of e936. A dominant mutation in the conserved C
      terminal domain of the C. elegans homolog of the human tri-snRNP 27K protein,
      which we have named SNRP-27, suppresses e936 uncoordination through changes in
      splicing. We propose that SMU-2, SMU-1, and SNRP-27 contribute to the fidelity of
      splice site choice after the initial identification of 5' splice sites by U1
      snRNP.

PMID- 19380479
TI  - Drosophila ISWI regulates the association of histone H1 with interphase
      chromosomes in vivo.
AB  - Although tremendous progress has been made toward identifying factors that
      regulate nucleosome structure and positioning, the mechanisms that regulate
      higher-order chromatin structure remain poorly understood. Recent studies suggest
      that the ISWI chromatin-remodeling factor plays a key role in this process by
      promoting the assembly of chromatin containing histone H1. To test this
      hypothesis, we investigated the function of H1 in Drosophila. The association of
      H1 with salivary gland polytene chromosomes is regulated by a dynamic, ATP
      dependent process. Reducing cellular ATP levels triggers the dissociation of H1
      from polytene chromosomes and causes chromosome defects similar to those
      resulting from the loss of ISWI function. H1 knockdown causes even more severe
      defects in chromosome structure and a reduction in nucleosome repeat length,
      presumably due to the failure to incorporate H1 during replication-dependent
      chromatin assembly. Our findings suggest that ISWI regulates higher-order
      chromatin structure by modulating the interaction of H1 with interphase
      chromosomes.

PMID- 19380480
TI  - Genetic analysis of zinc-finger nuclease-induced gene targeting in Drosophila.
AB  - Using zinc-finger nucleases (ZFNs) to cleave the chromosomal target, we have
      achieved high frequencies of gene targeting in the Drosophila germline. Both
      local mutagenesis through nonhomologous end joining (NHEJ) and gene replacement
      via homologous recombination (HR) are stimulated by target cleavage. In this
      study we investigated the mechanisms that underlie these processes, using
      materials for the rosy (ry) locus. The frequency of HR dropped significantly in
      flies homozygous for mutations in spnA (Rad51) or okr (Rad54), two components of
      the invasion-mediated synthesis-dependent strand annealing (SDSA) pathway. When
      single-strand annealing (SSA) was also blocked by the use of a circular donor
      DNA, HR was completely abolished. This indicates that the majority of HR proceeds
      via SDSA, with a minority mediated by SSA. In flies deficient in lig4 (DNA ligase
      IV), a component of the major NHEJ pathway, the proportion of HR products rose
      significantly. This indicates that most NHEJ products are produced in a lig4
      dependent process. When both spnA and lig4 were mutated and a circular donor was
      provided, the frequency of ry mutations was still high and no HR products were
      recovered. The local mutations produced in these circumstances must have arisen
      through an alternative, lig4-independent end-joining mechanism. These results
      show what repair pathways operate on double-strand breaks in this gene targeting
      system. They also demonstrate that the outcome can be biased toward gene
      replacement by disabling the major NHEJ pathway and toward simple mutagenesis by
      interfering with the major HR process.

PMID- 19380481
TI  - Novel types of Ca2+ release channels participate in the secretory cycle of
      Paramecium cells.
AB  - A database search of the Paramecium genome reveals 34 genes related to Ca(2+)
      release channels of the inositol-1,4,5-trisphosphate (IP(3)) or ryanodine
      receptor type (IP(3)R, RyR). Phylogenetic analyses show that these Ca(2+) release
      channels (CRCs) can be subdivided into six groups (Paramecium tetraurelia CRC-I
      to CRC-VI), each one with features in part reminiscent of IP(3)Rs and RyRs. We
      characterize here the P. tetraurelia CRC-IV-1 gene family, whose relationship to
      IP(3)Rs and RyRs is restricted to their C-terminal channel domain. CRC-IV-1
      channels localize to cortical Ca(2+) stores (alveolar sacs) and also to the
      endoplasmic reticulum. This is in contrast to a recently described true IP(3)
      channel, a group II member (P. tetraurelia IP(3)R(N)-1), found associated with
      the contractile vacuole system. Silencing of either one of these CRCs results in
      reduced exocytosis of dense core vesicles (trichocysts), although for different
      reasons. Knockdown of P. tetraurelia IP(3)R(N) affects trichocyst biogenesis,
      while CRC-IV-1 channels are involved in signal transduction since silenced cells
      show an impaired release of Ca(2+) from cortical stores in response to exocytotic
      stimuli. Our discovery of a range of CRCs in Paramecium indicates that protozoans
      already have evolved multiple ways for the use of Ca(2+) as signaling molecule.

PMID- 19380482
TI  - Alpha1-AMP-activated protein kinase regulates hypoxia-induced Na,K-ATPase
      endocytosis via direct phosphorylation of protein kinase C zeta.
AB  - Hypoxia promotes Na,K-ATPase endocytosis via protein kinase C zeta (PKC zeta)
      mediated phosphorylation of the Na,K-ATPase alpha subunit. Here, we report that
      hypoxia leads to the phosphorylation of 5'-AMP-activated protein kinase (AMPK) at
      Thr172 in rat alveolar epithelial cells. The overexpression of a dominant
      negative AMPK alpha subunit (AMPK-DN) construct prevented the hypoxia-induced
      endocytosis of Na,K-ATPase. The overexpression of the reactive oxygen species
      (ROS) scavenger catalase prevented hypoxia-induced AMPK activation. Moreover,
      hypoxia failed to activate AMPK in mitochondrion-deficient rho(0)-A549 cells,
      suggesting that mitochondrial ROS play an essential role in hypoxia-induced AMPK
      activation. Hypoxia-induced PKC zeta translocation to the plasma membrane and
      phosphorylation at Thr410 were prevented by the pharmacological inhibition of
      AMPK or by the overexpression of the AMPK-DN construct. We found that AMPK alpha
      phosphorylates PKC zeta on residue Thr410 within the PKC zeta activation loop.
      Importantly, the activation of AMPK alpha was necessary for hypoxia-induced AMPK
      PKC zeta binding in alveolar epithelial cells. The overexpression of T410A mutant
      PKC zeta prevented hypoxia-induced Na,K-ATPase endocytosis, confirming that PKC
      zeta Thr410 phosphorylation is essential for this process. PKC zeta activation by
      AMPK is isoform specific, as small interfering RNA targeting the alpha1 but not
      the alpha2 catalytic subunit prevented PKC zeta activation. Accordingly, we
      provide the first evidence that hypoxia-generated mitochondrial ROS lead to the
      activation of the AMPK alpha1 isoform, which binds and directly phosphorylates
      PKC zeta at Thr410, thereby promoting Na,K-ATPase endocytosis.

PMID- 19380483
TI  - Genome-wide mapping of boundary element-associated factor (BEAF) binding sites in
      Drosophila melanogaster links BEAF to transcription.
AB  - Insulator elements play a role in gene regulation that is potentially linked to
      nuclear organization. Boundary element-associated factors (BEAFs) 32A and 32B
      associate with hundreds of sites on Drosophila polytene chromosomes. We
      hybridized DNA isolated by chromatin immunoprecipitation to genome tiling
      microarrays to construct a genome-wide map of BEAF binding locations. A distinct
      difference in the association of 32A and 32B with chromatin was noted. We
      identified 1,820 BEAF peaks and found that more than 85% were less than 300 bp
      from transcription start sites. Half are between head-to-head gene pairs. BEAF
      associated genes are transcriptionally active as judged by the presence of RNA
      polymerase II, dimethylated histone H3 K4, and the alternative histone H3.3.
      Forty percent of these genes are also associated with the polymerase negative
      elongation factor NELF. Like NELF-associated genes, most BEAF-associated genes
      are highly expressed. Using quantitative reverse transcription-PCR, we found that
      the expression levels of most BEAF-associated genes decrease in embryos and
      cultured cells lacking BEAF. These results provide an unexpected link between
      BEAF and transcription, suggesting that BEAF plays a role in maintaining most
      associated promoter regions in an environment that facilitates high transcription
      levels.

PMID- 19380484
TI  - The active form of human aryl hydrocarbon receptor (AHR) repressor lacks exon 8,
      and its Pro 185 and Ala 185 variants repress both AHR and hypoxia-inducible
      factor.
AB  - The aryl hydrocarbon receptor (AHR) repressor (AHRR) inhibits AHR-mediated
      transcription and has been associated with reproductive dysfunction and
      tumorigenesis in humans. Previous studies have characterized the repressor
      function of AHRRs from mice and fish, but the human AHRR ortholog (AHRR(715))
      appeared to be nonfunctional in vitro. Here, we report a novel human AHRR cDNA
      (AHRRDelta8) that lacks exon 8 of AHRR(715). AHRRDelta8 was the predominant AHRR
      form expressed in human tissues and cell lines. AHRRDelta8 effectively repressed
      AHR-dependent transactivation, whereas AHRR(715) was much less active. Similarly,
      AHRRDelta8, but not AHRR(715), formed a complex with AHR nuclear translocator
      (ARNT). Repression of AHR by AHRRDelta8 was not relieved by overexpression of
      ARNT or AHR coactivators, suggesting that competition for these cofactors is not
      the mechanism of repression. AHRRDelta8 interacted weakly with AHR but did not
      inhibit its nuclear translocation. In a survey of transcription factor
      specificity, AHRRDelta8 did not repress the nuclear receptor pregnane X receptor
      or estrogen receptor alpha but did repress hypoxia-inducible factor (HIF)
      dependent signaling. AHRRDelta8-Pro(185) and -Ala(185) variants, which have been
      linked to human reproductive disorders, both were capable of repressing AHR or
      HIF. Together, these results identify AHRRDelta8 as the active form of human AHRR
      and reveal novel aspects of its function and specificity as a repressor.

PMID- 19380485
TI  - Dynamin reduces Pyk2 Y402 phosphorylation and SRC binding in osteoclasts.
AB  - Signaling via the Pyk2-Src-Cbl complex downstream of integrins contributes to the
      assembly, organization, and dynamics of podosomes, which are the transient
      adhesion complexes of highly motile cells such as osteoclasts and dendritic
      cells. We previously demonstrated that the GTPase dynamin is associated with
      podosomes, regulates actin flux in podosomes, and promotes bone resorption by
      osteoclasts. We report here that dynamin associates with Pyk2, independent of
      dynamin's GTPase activity, and reduces Pyk2 Y402 phosphorylation in a GTPase
      dependent manner, leading to decreased Src binding to Pyk2. Overexpressing
      dynamin decreased the macrophage colony-stimulating factor- and adhesion-induced
      phosphorylation of Pyk2 in osteoclastlike cells, suggesting that dynamin is
      likely to regulate Src-Pyk2 binding downstream of integrins and growth factor
      receptors with important cellular consequences. Furthermore, catalytically active
      Src promotes dynamin-Pyk2 association, and mutating specific Src-phosphorylated
      tyrosine residues in dynamin blunts the dynamin-induced decrease in Pyk2
      phosphorylation. Thus, since Src binds to Pyk2 through its interaction with
      phospho-Y402, our results suggest that Src activates a negative-feedback loop
      downstream of integrin engagement and other stimuli by promoting both the binding
      of dynamin to Pyk2-containing complexes and the dynamin-dependent decrease in
      Pyk2 Y402 phosphorylation, ultimately leading to the dissociation of Src from
      Pyk2.

PMID- 19380486
TI  - Caspase-10-mediated heat shock protein 90 beta cleavage promotes UVB irradiation
      induced cell apoptosis.
AB  - Heat shock protein 90 beta (Hsp90 beta) is involved in many cellular functions.
      However, the posttranslational modification of Hsp90 beta, especially in response
      to apoptotic stimulation, is not well understood. In this study, we found that
      Hsp90 beta was cleaved by activated caspase-10 under UVB irradiation. Caspase-10
      activation, in turn, depended on caspase-8, which cleaved caspase-10 directly.
      Autocrine secretion of FAS ligand and upregulated FAS expression induced by UVB
      irradiation contributed to activation of caspase-10, which cleaved Hsp90 beta at
      D278, P293, and D294. The downregulation of Hsp90 beta mediated by caspase-8
      dependent caspase-10 activation promoted UVB-induced cell apoptosis.

PMID- 19380488
TI  - Locally, meiotic double-strand breaks targeted by Gal4BD-Spo11 occur at discrete
      sites with a sequence preference.
AB  - Meiotic recombination is initiated by DNA double-strand breaks (DSBs) that are
      catalyzed by the type II topoisomerase-like Spo11 protein. Locally, at
      recombination hot spots, Spo11 introduces DSBs at multiple positions within
      approximately 75 to 250 bp, corresponding to accessible regions of the chromatin.
      The molecular basis of this multiplicity of cleavage positions, observed in a
      population of meiotic cells, remains elusive. To address this issue, we have
      examined the properties of the Gal4BD-Spo11 fusion protein, which targets meiotic
      DSBs to regions with Gal4 binding sites (UAS). By single-nucleotide resolution
      mapping of targeted DSBs, we found that DSB formation was restricted to discrete
      sites approximately 20 nucleotides from the UAS, defining a "DSB targeting
      window." Thus, the multiplicity of cleavage positions at natural Spo11 hot spots
      likely represents binding of Spo11 to different distinct sites within the
      accessible DNA region in each different meiotic cell. Further, we showed that
      mutations in the Spo11 moiety affected the DSB distribution in the DSB targeting
      window and that mutations in the DNA at the Spo11 cleavage site affected DSB
      position. These results demonstrate that Spo11 itself has sequence preference and
      contributes to the choice of DSB positions.

PMID- 19380487
TI  - Topoisomerase II alpha is required for embryonic development and liver
      regeneration in zebrafish.
AB  - Topoisomerases solve the topological problems encountered by DNA throughout the
      lifetime of a cell. Topoisomerase II alpha, which is highly conserved among
      eukaryotes, untangles replicated chromosomes during mitosis and is absolutely
      required for cell viability. A homozygous lethal mutant, can4, was identified in
      a screen to identify genes important for cell proliferation in zebrafish by
      utilizing an antibody against a mitosis-specific marker, phospho-histone H3.
      Mutant embryos have a decrease in the number of proliferating cells and display
      increases in DNA content and apoptosis, as well as mitotic spindle defects.
      Positional cloning revealed that the genetic defect underlying these phenotypes
      was the result of a mutation in the zebrafish topoisomerase II alpha (top2a)
      gene. top2a was found to be required for decatenation but not for condensation in
      embryonic mitoses. In addition to being required for development, top2a was found
      to be a haploinsufficient regulator of adult liver regrowth in zebrafish.
      Regeneration analysis of other adult tissues, including fins, revealed no
      heterozygous phenotype. Our results confirm a conserved role for TOP2A in
      vertebrates as well as a dose-sensitive requirement for top2a in adults.

PMID- 19380489
TI  - HIS-24 linker histone and SIR-2.1 deacetylase induce H3K27me3 in the
      Caenorhabditis elegans germ line.
AB  - HIS-24 linker histone and SIR-2.1 deacetylase are involved in chromatin silencing
      in Caenorhabditis elegans. Depletion of SIR-2.1 results in cytoplasmic retention
      of HIS-24 in oocytes. However, the molecular working mechanisms of HIS-24 and SIR
      2.1 are unclear. We show here a synergistic function of SIR-2.1 and HIS-24 that
      are together essential for maintenance of the H3K27me3 mark in the germ line of
      C. elegans. We demonstrate the synthetic effects of the two factors on brood
      size, embryogenesis, and fertility. SIR-2.1 and HIS-24 associate with the
      subtelomeric regions but apparently do not interact directly. We report that SIR
      2.1 deacetylates H3K9 at subtelomeric regions and suggest that deacetylation of
      H3K9 is a prerequisite for H3K27 methylation. In turn, we found that HIS-24
      specifically interacts with the histone H3 K27 region, when unmodified or in the
      trimethylated state. Overall, our data indicate that SIR-2.1 and HIS-24
      contribute to the propagation of a specialized chromatin state at the
      subtelomeric regions and elsewhere in the genome.

PMID- 19380490
TI  - ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to
      promote transformation.
AB  - Several ETS transcription factors, including ELF4/MEF, can function as oncogenes
      in murine cancer models and are overexpressed in human cancer. We found that
      Elf4/Mef activates Mdm2 expression; thus, lack of or knockdown of Elf4/Mef
      reduces Mdm2 levels in mouse embryonic fibroblasts (mef's), leading to enhanced
      p53 protein accumulation and p53-dependent senescence. Even though p53 is absent
      in Elf4(-/-) p53(-/-) mef's, neither oncogenic H-Ras(V12) nor c-myc can induce
      transformation of these cells. This appears to relate to the INK4a/ARF locus;
      both p19(ARF) and p16 are increased in Elf4(-/-) p53(-/-) mef's, and expression
      of Bmi-1 or knockdown of p16 in this context restores H-Ras(V12)-induced
      transformation. Thus, ELF4/MEF promotes tumorigenesis by inhibiting both the p53
      and p16/Rb pathways.

PMID- 19380491
TI  - Ubiquitin-regulated recruitment of IkappaB kinase epsilon to the MAVS interferon
      signaling adapter.
AB  - Induction of the antiviral interferon response is initiated upon recognition of
      viral RNA structures by the RIG-I or Mda-5 DEX(D/H) helicases. A complex
      signaling cascade then converges at the mitochondrial adapter MAVS, culminating
      in the activation of the IRF and NF-kappaB transcription factors and the
      induction of interferon gene expression. We have previously shown that MAVS
      recruits IkappaB kinase epsilon (IKKepsilon) but not TBK-1 to the mitochondria
      following viral infection. Here we map the interaction of MAVS and IKKepsilon to
      the C-terminal region of MAVS and demonstrate that this interaction is ubiquitin
      dependent. MAVS is ubiquitinated following Sendai virus infection, and K63-linked
      ubiquitination of lysine 500 (K500) of MAVS mediates recruitment of IKKepsilon to
      the mitochondria. Real-time PCR analysis reveals that a K500R mutant of MAVS
      increases the mRNA level of several interferon-stimulated genes and correlates
      with increased NF-kappaB activation. Thus, recruitment of IKKepsilon to the
      mitochondria upon MAVS K500 ubiquitination plays a modulatory role in the cascade
      leading to NF-kappaB activation and expression of inflammatory and antiviral
      genes. These results provide further support for the differential role of
      IKKepsilon and TBK-1 in the RIG-I/Mda5 pathway.

PMID- 19380492
TI  - The yeast GATA factor Gat1 occupies a central position in nitrogen catabolite
      repression-sensitive gene activation.
AB  - Saccharomyces cerevisiae cells are able to adapt their metabolism according to
      the quality of the nitrogen sources available in the environment. Nitrogen
      catabolite repression (NCR) restrains the yeast's capacity to use poor nitrogen
      sources when rich ones are available. NCR-sensitive expression is modulated by
      the synchronized action of four DNA-binding GATA factors. Although the first
      identified GATA factor, Gln3, was considered the major activator of NCR-sensitive
      gene expression, our work positions Gat1 as a key factor for the integrated
      control of NCR in yeast for the following reasons: (i) Gat1 appeared to be the
      limiting factor for NCR gene expression, (ii) GAT1 expression was regulated by
      the four GATA factors in response to nitrogen availability, (iii) the two
      negative GATA factors Dal80 and Gzf3 interfered with Gat1 binding to DNA, and
      (iv) Gln3 binding to some NCR promoters required Gat1. Our study also provides
      mechanistic insights into the mode of action of the two negative GATA factors.
      Gzf3 interfered with Gat1 by nuclear sequestration and by competition at its own
      promoter. Dal80-dependent repression of NCR-sensitive gene expression occurred at
      three possible levels: Dal80 represses GAT1 expression, it competes with Gat1 for
      binding, and it directly represses NCR gene transcription.

PMID- 19380493
TI  - Human DNA polymerase eta is required for common fragile site stability during
      unperturbed DNA replication.
AB  - Human DNA polymerase eta (Pol eta) modulates susceptibility to skin cancer by
      promoting translesion DNA synthesis (TLS) past sunlight-induced cyclobutane
      pyrimidine dimers. Despite its well-established role in TLS synthesis, the role
      of Pol eta in maintaining genome stability in the absence of external DNA damage
      has not been well explored. We show here that short hairpin RNA-mediated
      depletion of Pol eta from undamaged human cells affects cell cycle progression
      and the rate of cell proliferation and results in increased spontaneous
      chromosome breaks and common fragile site expression with the activation of ATM
      mediated DNA damage checkpoint signaling. These phenotypes were also observed in
      association with modified replication factory dynamics during S phase. In
      contrast to that seen in Pol eta-depleted cells, none of these cellular or
      karyotypic defects were observed in cells depleted for Pol iota, the closest
      relative of Pol eta. Our results identify a new role for Pol eta in maintaining
      genomic stability during unperturbed S phase and challenge the idea that the sole
      functional role of Pol eta in human cells is in TLS DNA damage tolerance and/or
      repair pathways following exogenous DNA damage.

PMID- 19380494
TI  - Errors in multi-digit arithmetic and behavioral inattention in children with math
      difficulties.
AB  - Errors in written multi-digit computation were investigated in children with math
      difficulties. Third- and fourth-grade children (n = 291) with coexisting math and
      reading difficulties, math difficulties, reading difficulties, or no learning
      difficulties were compared. A second analysis compared those with severe math
      learning difficulties, low average achievement in math, and no learning
      difficulties. Math fact errors were related to the severity of the math
      difficulties, not to reading status. Contrary to predictions, children with
      poorer reading, regardless of math achievement, committed more visually based
      errors. Operation switch errors were not systematically related to group
      membership. Teacher ratings of behavioral inattention were related to accuracy,
      math fact errors, and procedural bugs. The findings are discussed with respect to
      hypotheses about the cognitive origins of arithmetic errors and in relation to
      current discussions about how to conceptualize math disabilities.

PMID- 19380495
TI  - Working memory in children with developmental disorders.
AB  - The aim of the present study was to directly compare working memory skills across
      students with different developmental disorders to investigate whether the
      uniqueness of their diagnosis would impact memory skills. The authors report
      findings confirming differential memory profiles on the basis of the following
      developmental disorders: Specific Language Impairment, Developmental Coordination
      Disorder (DCD), Attention-Deficit/Hyperactivity Disorder, and Asperger syndrome
      (AS). Specifically, language impairments were associated with selective deficits
      in verbal short-term and working memory, whereas motor impairments (DCD) were
      associated with selective deficits in visuospatial short-term and working memory.
      Children with attention problems were impaired in working memory in both verbal
      and visuospatial domains, whereas the children with AS had deficits in verbal
      short-term memory but not in any other memory component. The implications of
      these findings are discussed in light of support for learning.

PMID- 19380496
TI  - Exposure to polybrominated diphenyl ethers 203 and 206 during the neonatal brain
      growth spurt affects proteins important for normal neurodevelopment in mice.
AB  - The period of rapid brain growth and development (BGS) is postnatal in mice and
      rats, spanning the first 3-4 weeks of life, reaching its peak around postnatal
      day 10, whereas in humans, the BGS is perinatal. CaMKII, GAP-43, synaptophysin,
      and tau play important roles during the BGS. One class of flame retardants,
      polybrominated diphenyl ethers (PBDEs), is present and increasing in the
      environment and in human milk. The only congener still in use, decabrominated
      diphenyl ether (PBDE 209), is thought to be debrominated into lower brominated
      congeners. In the present study, nona- and octabrominated PBDEs were examined.
      Neonatal mice were exposed to 21 mumol PBDE 203 or 206/kg bodyweight on postnatal
      day 10, and different brain regions were analyzed for CaMKII, GAP-43,
      synaptophysin, and tau, 24 h after exposure. The protein analysis showed that
      CaMKII and synaptophysin increased significantly in the hippocampus, but not in
      the cerebral cortex, after neonatal exposure to PBDE 203 or 206. Furthermore,
      there were no significant changes in the levels of GAP-43 and tau in the cerebral
      cortex or hippocampus after neonatal exposure to PBDE 203 or 206. This shows that
      PBDE 203 and 206 affect important proteins involved in normal maturation of the
      brain and strengthens our findings that highly brominated PBDEs cause
      developmental neurotoxicity. In addition, the increases in CaMKII and
      synaptophysin are the same changes seen after neonatal PBDE 209 exposure;
      supporting the suggestion that PBDE 209 must be metabolized, likely debrominated
      into lower brominated PBDEs, to exert its neurotoxic effects.

PMID- 19380497
TI  - "Going beyond your data," and other dilemmas of interpretation.

PMID- 19380498
TI  - How adolescents experience smoking cessation.
AB  - In this study we develop a model of how youth experience smoking cessation
      attempts. We followed 15 adolescent smokers twice monthly over three months.
      Through six semistructured interviews, we explored participants' subjective
      experiences of making a "quit" attempt. We analyzed transcript data using
      grounded theory procedures, beginning with open coding, axial coding,
      construction of matrices, and development of a preliminary theory or model of
      this phenomenon. We found that only emotionally compelling and inescapable quit
      reasons were truly motivating. Few parents actively supported their child during
      quit attempts; smoking friends and other peers undermined them. All successful
      quitters established new, nonsmoking friends and completely redefined themselves.
      The quit experience was physically uncomfortable, emotionally distressful, and
      socially isolating. Greater motivation, mature problem-solving skills, and a
      willingness to supplant their smoking friends characterized successful quitters.
      Further research is needed to test this model's efficacy in the adolescent
      population.

PMID- 19380499
TI  - Gaps between patients, media, and academic medicine in discourses on gender and
      depression: a metasynthesis.
AB  - For reasons that are not yet fully understood, depression affects women twice as
      often as men. In this article we describe an investigation of how depression is
      understood in relation to men and women by the patients themselves, the media,
      and the medical research establishment. We do this by undertaking a metasynthesis
      of data from three different sources: interviews with depressed patients, media
      portrayals of depressed individuals in Sweden, and international medical articles
      about depression. The findings reveal that there are differences in (a) the
      recognition of depression, (b) the understanding of the reasons for depression,
      and (c) the contextualization of depression. Although women and men describe
      different symptoms and reasons for falling ill, these gendered expressions are
      not acknowledged in articles coming from Western medical settings. We discuss the
      implications of these findings and conclude that an integrated model for
      understanding biological, gender, and cultural aspects of depression has yet to
      be developed.

PMID- 19380500
TI  - The role of the media in influencing children's nutritional perceptions.
AB  - Recently the mass media environment of children, in particular food advertising,
      has come under scrutiny as a contributing factor in the increasing prevalence of
      childhood obesity. Focus groups were used to explore how children's appraisals of
      various forms of media inform their health-related perceptions about eating and
      nutrition. Ninety participants aged 10 to 12 years were recruited from schools
      throughout Auckland, New Zealand. Schools were randomly selected from among those
      rated with low, medium, and high socioeconomic status. Results show that the
      media is a key factor shaping how young people conceptualize healthy eating and
      healthy bodies. Mass media food messages were not seen as a credible source of
      health information; rather, they assist in constructing and reinforcing dominant
      misconceptions about food, healthy eating, and nutrition. Nutritional messages
      embedded in both health promotion and advertising were perceived to be
      conflicting and ambiguous, and might serve to undermine the trustworthiness of
      health promotion initiatives.

PMID- 19380501
TI  - From feeling too little and too much, to feeling more and less? A nonparadoxical
      theory of the functions of self-harm.
AB  - It is widely agreed that one of the functions of self-harm by cutting or burning
      the body is to regulate emotion. There is an apparent paradox in the emotion
      regulative function of self-harm: some people are using self-harm to both
      increase and decrease affect. The aim of this study, which followed the
      principles of the grounded theory approach, was to generate a paradox-free theory
      of the functions of self-harm that is of immediate relevance to the participants
      themselves, who are often confused about the behavior and the experiences
      preceding it. We found that "feeling too little" and "feeling too much" share
      characteristics in three categories of experience: emotional awareness, sense of
      self/reality, and body-based experience. We explain the functions of self-harm in
      terms of body-based experience: Self-harm resolves a state of psychosomatic
      suspension and increases the extent to which the body is involved in the
      experience of emotion.

PMID- 19380502
TI  - Breast cancer patients' experience of external-beam radiotherapy.
AB  - Radiotherapy is a critical component of treatment for the majority of women with
      breast cancer, particularly those who receive breast conserving surgery. Although
      medically beneficial, radiotherapy can take a physical and psychological toll on
      patients. However, little is known about the specific thoughts and feelings
      experienced by women undergoing breast cancer radiotherapy. Therefore, the study
      aim was to use qualitative research methods to develop an understanding of these
      thoughts and feelings based on 180 diary entries completed during radiotherapy by
      15 women with stage 0 to stage III breast cancer. Thematic analysis identified
      four primary participant concerns: (a) a preoccupation with time, (b) fantasies
      (both optimistic and pessimistic) about life following radiotherapy, (c) the toll
      their side-effect experience takes on their self-esteem, and (d) feeling
      mystified by radiotherapy. These themes are consistent with previous literature
      on illness and identity. These findings have implications for the treatment and
      care of women undergoing breast cancer radiotherapy.

PMID- 19380503
TI  - Exploring resources for physical activity in Hispanic women, using photo
      elicitation.
AB  - Addressing cultural, social, and contextual resources to promote physical
      activity behavior among Hispanic women is necessary to establish effective
      intervention approaches. With this research we intended to (a) explore cultural,
      social, and contextual resources for physical activity among Hispanic women; and
      (b) evaluate the acceptability of visual methods as an innovative, formative
      method to enhance intervention relevance. A qualitative descriptive
      methodological design incorporating photo elicitation was used with 7 Hispanic
      women, aged 23 to 60 (X = 44.2). Results were varied, and themes captured
      cultural, social, and contextual resources. Culture provided an overarching
      perspective, guiding identification and choice of physical activity resources,
      support, and setting. Themes included being active as a way of life,
      acknowledging tradition, moving with me, creating place, and building resources.
      Photo elicitation was evaluated as an acceptable method. Data provide an initial
      step toward generating a more complete understanding of perceived resources for
      physical activity in Hispanic women, and support the acceptability of photo
      elicitation.

PMID- 19380504
TI  - Cultural changes in ICU sedation management.
AB  - The aim of this study was to explore physicians' views and perceptions of
      sedation, and offer a new approach to the understanding of issues of sedation. I
      used a qualitative, descriptive, and explorative multicenter design. Data were
      generated by seven key-informant interviews using a semistructured interview
      guide. One experienced doctor was selected at each of the seven largest intensive
      care units in Denmark. Interpretational analysis was performed by comprehensive
      overview, individual case analysis, cross-case analysis, and integrated thematic
      analysis and identification of emerging themes. The following themes emerged: a
      paradigm shift from sedated to more awake and comfortable patients, cultural
      changes toward intracollegial openness, increased interdisciplinary and
      staff/patient/family collaboration, patient and environmental normalization, and
      humanization. The study findings provide an understanding of contextual issues of
      sedation, safety, and comfort, and suggest that a cultural change in sedation
      strategies might reduce the duration of sedation and mechanical ventilation while
      containing cost and improving the well-being of the patients.

PMID- 19380505
TI  - Rethinking recovery from eating disorders: spiritual and political dimensions.
AB  - In this article, we portray women's experiences of long-term recovery from
      anorexia and compulsive overeating. Semistructured interviewing and an
      interpretive biographical method were used to coconstruct accounts of each
      participant's transition to wellness. Thick descriptions of self-identified
      turning points on the path to recovery are framed in terms of the concept of
      personal positioning in relation to cultural master narratives. The narratives
      suggest that long-term recovery involves spiritual or political commitment and
      purposeful engagement with communities larger than the self.

PMID- 19380506
TI  - The politics of conducting research on depression in a cross-cultural context.
AB  - Successful community engagement is often a crucial component of effective
      qualitative research. In this article we reflect on our experience of engaging
      with ethnic minority communities in a qualitative study of help seeking for
      depression. Community engagement emerges as a complex process that provides
      important insights into the way mental illness is constructed in various cultural
      contexts and from diverse perspectives. Contested notions of ethnicity, culture,
      community, and depression were the domains in which personal and public politics
      were played out. We worked with bilingual research assistants who provided an
      entree to the community. Despite this, disparate community subgroups and
      influential individuals vied for input into and control of the research agenda.
      We conclude that negotiating the politics of these processes requires great
      reflexivity and is itself a powerful seam of data, adding richness to findings
      about the experience of mental distress in a community seeking to locate itself
      within mainstream society.

PMID- 19380507
TI  - Stability of ecosystem: global properties of a general predator-prey model.
AB  - Establishing the conditions for the stability of ecosystems and for stable
      coexistence of interacting populations is a problem of the highest priority in
      mathematical biology. This problem is usually considered under specific
      assumptions made regarding the functional forms of non-linear feedbacks. However,
      there is growing understanding that this approach has a number of major
      deficiencies. The most important of these is that the precise forms of the
      functional responses involved in the model are unknown in detail, and we can
      hardly expect that these will be known in feasible future. In this paper, we
      consider the dynamics of two species with interaction of consumer-supplier (prey
      predator) type. This model generalizes a variety of models of population
      dynamics, including a range of prey-predator models, SIR and SIRS epidemic
      models, chemostat models, etc. We assume that the functional responses that are
      usually included in such models are given by unspecified functions. Using the
      direct Lyapunov method, we derive the conditions which ensure global asymptotic
      stability of this general model. It is remarkable that these conditions impose
      much weaker constraints on the system properties than that are usually assumed.
      We also identify the parameter that allows us to distinguish between existence
      and non-existence of the coexisting steady state.

PMID- 19380508
TI  - Patient-centered tinnitus management tool: a clinical audit.
AB  - PURPOSE: To evaluate the impact of an educational poster describing treatment
      options available to patients experiencing tinnitus. METHOD: A patient-centered
      tinnitus management tool (PCTMT) was developed in the form of an educational
      poster that encouraged patients to decide how they wanted to deal with their
      tinnitus from the following options: (a) ignore the tinnitus and forget about it,
      (b) use a sound generator, (c) undertake tinnitus counseling with an expert, or
      (d) deal with the tinnitus using hearing aids (in the case of tinnitus and
      hearing loss). Fifty-five patients who were referred to the audiology department
      of a London hospital from the ENT department for tinnitus counseling were asked
      to read the PCTMT and to choose the option(s) that suited them the best. RESULTS:
      Forty-two percent of the patients wished to undertake counseling, 9% decided to
      try to ignore their tinnitus without help, 26% wanted to deal with their tinnitus
      with the help of a sound generator, and 24% decided to use hearing aids.
      CONCLUSIONS: The PCTMT reduced the number of patients who would otherwise have
      been referred for tinnitus counseling by 58%. This reduced the length of the
      waiting list and increased the time available for counseling of those patients
      who wanted it.

PMID- 19380509
TI  - Do experienced hearing aid users know how to use their hearing AIDS correctly?
AB  - PURPOSE: To assess experienced hearing aid users' ability to use their hearing
      aids correctly. METHOD: In this study, we developed the Practical Hearing Aid
      Skills Test (PHAST) to objectively test a hearing aid user's ability to
      manipulate his or her hearing aids. The PHAST requires hearing aid users to
      perform 8 hearing aid care and use tasks that are basic skills typically taught
      to new hearing aid users at the time of their hearing aid fitting. The PHAST was
      administered to a group of 50 experienced hearing aid users. In addition,
      participants were administered questionnaires about hearing aid satisfaction
      (i.e., Satisfaction With Amplification in Daily Life; R. M. Cox & G. C.
      Alexander, 1999), benefit (i.e., Abbreviated Profile of Hearing Aid Benefit; R.
      M. Cox & G. C. Alexander, 1995), and use. RESULTS: Participants' performance on
      the PHAST ranged from 48% to 100%, and the scores were normally distributed
      around the mean (78.56%). No significant relationship was observed between the
      PHAST and any of the other tests administered in this study. The only variable
      significantly associated with participants' performance on the PHAST was age.
      CONCLUSIONS: Results from this study suggest that experienced hearing aid users
      range from having an excellent understanding of how to use their hearing aids to
      a poor understanding. The variability in performance among experienced hearing
      aid users highlights the importance of directly assessing a client's ability to
      use his or her hearing aids.

PMID- 19380510
TI  - An enzymatically inactivated hemoglobinase from Necator americanus induces
      neutralizing antibodies against multiple hookworm species and protects dogs
      against heterologous hookworm infection.
AB  - Hookworms digest hemoglobin from erythrocytes via a proteolytic cascade that
      begins with the aspartic protease, APR-1. Ac-APR-1 from the dog hookworm,
      Ancylostoma caninum, protects dogs against hookworm infection via antibodies that
      neutralize enzymatic activity and interrupt blood-feeding. Toward developing a
      human hookworm vaccine, we expressed both wild-type (Na-APR-1(wt)) and mutant (Na
      APR-1(mut)-mutagenesis of the catalytic aspartic acids) forms of Na-APR-1 from
      the human hookworm, Necator americanus. Refolded Na-APR-1(wt) was catalytically
      active, and Na-APR-1(mut) was catalytically inactive but still bound substrates.
      Vaccination of canines with Na-APR-1(mut) and heterologous challenge with A.
      caninum resulted in significantly reduced parasite egg burdens (P=0.034) and
      weight loss (P=0.022). Vaccinated dogs also had less gut pathology, fewer adult
      worms, and reduced blood loss compared to controls but these did not reach
      statistical significance. Vaccination with Na-APR-1(mut) induced antibodies that
      bound the native enzyme in the parasite gut and neutralized enzymatic activity of
      Na-APR-1(wt) and APR-1 orthologues from three other hookworm species that infect
      humans. IgG1 against Na-APR-1(mut) was the most prominently detected antibody in
      sera from people resident in high-transmission areas for N. americanus,
      indicating that natural boosting may occur in exposed humans. Na-APR-1(mut) is
      now a lead antigen for the development of an antihematophagy vaccine for human
      hookworm disease.

PMID- 19380511
TI  - CXCR3 activation by lentivirus infection suppresses neuronal autophagy:
      neuroprotective effects of antiretroviral therapy.
AB  - Previous studies have implicated CXCL12 in the neuropathogenesis of HIV
      infection. Proteolysis of CXCL12 generates a neurotoxic molecule, CXCL12(5-67),
      which engages and activates CXCR3, in addition to exhibiting increased expression
      in the brains of patients with HIV-associated dementia (HAD). Herein, we
      investigated CXCR3-mediated neuronal injury, particularly, its contribution to
      autophagy suppression and the concomitant effects of antiretroviral therapy using
      human brain samples and models of HIV neuropathogenesis. Neurons in the brains of
      HAD patients and feline immunodeficiency virus (FIV)-infected animals, as well as
      cultured human neurons, expressed CXCR3, which was modulated in a ligand-specific
      manner. Exposure of human neurons to CXCL12(5-67) caused a reduction in the
      autophagy-associated molecule LC3 (P<0.05) and neuronal survival (P<0.05), which
      recapitulated findings in FIV- and HIV-infected brains (P<0.05). Oral didanosine
      (ddI) treatment of FIV-infected animals reduced neurobehavioral abnormalities in
      conjunction with diminished plasma viral load (P<0.05). F4/80 transcript
      abundance and CXCL12(5-67) immunoreactivity were reduced with restored neuronal
      LC3 expression in the brains of FIV-infected animals after ddI treatment
      (P<0.05). ddI treatment also prevented microglial activation and depletion of
      synaptic proteins in the cortex of FIV-infected animals (P<0.05). These findings
      indicate that the beneficial effects of ddI might be a consequence of a reduced
      systemic viral burden and concurrent leukocyte activation, leading to diminished
      neuroinflammation with preservation of neuronal autophagy by regulating CXCR3
      activation.

PMID- 19380513
TI  - A national study on the development of visual attention using the cognitive
      assessment system.
AB  - OBJECTIVE: Developmental changes in the performance of children and adolescents
      are studied using the Cognitive Assessment System (CAS) which is an individually
      administered test of 4 basic cognitive processes. METHOD: The test measures the
      Planning, Attention, Simultaneous, and Successive (PASS) processes as a theory of
      intelligence that can provide the framework for an alternative to traditional IQ
      tests. The CAS, which includes a scale of attention comprising 3 subtests, each
      of which is presented visually, provides an opportunity to study the development
      of visual attention for 2,200 children and adolescents aged 5- to 17-years-old
      who participated in the national standardization sample. A subsample ( n = 1,395)
      is also administered the Woodcock-Johnson Tests of Achievement - Revised (WJ-R).
      RESULTS: On all 3 CAS attention subtests, the mean scores improve with age, and
      the rate of change between adjacent age groups is moderate-to-large up to 15
      years-old. At all ages the CAS Attention standard score is moderately related to
      WJ-R Achievement Cluster scores. CONCLUSION: The results are discussed in light
      of conclusions about the development of attention based on the standardization
      sample of the NEPSY-A Developmental Neuropsychological Assessment.

PMID- 19380512
TI  - Novel endogenous peptide agonists of cannabinoid receptors.
AB  - Hemopressin (Hp), a 9-residue alpha-hemoglobin-derived peptide, was previously
      reported to function as a CB(1) cannabinoid receptor antagonist (1) . In this
      study, we report that mass spectrometry (MS) data from peptidomics analyses of
      mouse brain extracts identified N-terminally extended forms of Hp containing
      either three (RVD-Hpalpha) or two (VD-Hpalpha) additional amino acids, as well as
      a beta-hemoglobin-derived peptide with sequence similarity to that of hemopressin
      (VD-Hpbeta). Characterization of the alpha-hemoglobin-derived peptides using
      binding and functional assays shows that in contrast to Hp, which functions as a
      CB(1) cannabinoid receptor antagonist, both RVD-Hpalpha and VD-Hpalpha function
      as agonists. Studies examining the increase in the phosphorylation of ERK1/2
      levels or release of intracellular Ca(2+) indicate that these peptides activate a
      signal transduction pathway distinct from that activated by the endocannabinoid,
      2-arachidonoylglycerol, or the classic CB(1) agonist, Hu-210. This finding
      suggests an additional mode of regulation of endogenous cannabinoid receptor
      activity. Taken together, these results suggest that the CB(1) receptor is
      involved in the integration of signals from both lipid- and peptide-derived
      signaling molecules.

PMID- 19380514
TI  - Attention deficit/hyperactivity disorder in children and adolescents with autism
      spectrum disorder: symptom or syndrome?
AB  - OBJECTIVE: This study aims to evaluate ADHD-like symptoms in children with autism
      spectrum disorder (ASD) based on single-item analysis, as well as the comparison
      of two ASD subsamples of children with ADHD (ASD+) and without ADHD (ASD-).
      METHODS: Participants are 83 children with ASD. Dimensional and categorical
      aspects of ADHD are evaluated using a diagnostic symptom checklist according to
      DSM-IV. RESULTS: Of the sample, 53% fulfill DSM-IV criteria for ADHD. The
      comparison of the ASD+ and the ASD- samples reveals differences in age and IQ.
      Correlations of ADHD and PDD show significant results for symptoms of
      hyperactivity with impairment in communication and for inattention with
      stereotyped behavior. Item profiles of ADHD symptoms in the ASD+ sample are
      similar to those in a pure ADHD sample. CONCLUSION: The results of our study
      reveal a high phenotypical overlap between ASD and ADHD. The two identified
      subtypes, inattentive-stereotyped and hyperactive-communication impaired, reflect
      the DSM classification and may theoretically be a sign of two different
      neurochemical pathways, a dopaminergic and a serotonergic.

PMID- 19380515
TI  - Attention deficit hyperactivity disorder erroneously diagnosed and treated as
      bipolar disorder.
AB  - OBJECTIVE: There is a dearth of literature on patients erroneously diagnosed and
      treated for bipolar disorder. METHOD: The authors report a case of an adult with
      attention deficit hyperactivity disorder erroneously diagnosed and treated for
      bipolar disorder for 6 years. At that point, methylphenidate was initiated. The
      patient was judged to be a good treatment responder with improvements noted in
      the clinical global impressions severity scale. It was seen that the improvement
      was maintained at a 6-month follow-up. CONCLUSION: The present case reflects the
      importance of careful differential diagnosis when evaluating for bipolar
      disorder.

PMID- 19380516
TI  - Comorbidity of enuresis in children with attention-deficit/hyperactivity
      disorder.
AB  - OBJECTIVE: To compare parental psychopathology and psychiatric disorders in ADHD
      children with and those without enuresis. METHOD: The participants of the
      clinical sample interviewed according to DSM-IV diagnostic criteria were 35
      children with ADHD and enuresis, 153 ADHD children without enuresis, 115 fathers,
      and 172 mothers. RESULTS: Only ODD comorbidity was the predictor of enuresis.
      Conduct disorder, tic disorder, major depressive disorder, separation anxiety
      disorder, bruxism, generalized anxiety disorder, obsessive compulsive disorder,
      and nail biting were not statistically more frequent in ADHD children with
      enuresis than in the ADHD children without enuresis. The only parental
      psychiatric disorder that was related to the groups was father's major depressive
      disorder. CONCLUSION: Enuresis in ADHD has a relationship with ODD. Physicians
      who treat patients with ADHD and enuresis should routinely inquire about the
      presence of major depression in the fathers. (J. of Att. Dis. 2010; 13(5) 464
      467).

PMID- 19380517
TI  - Testing the prediction error difference between 2 predictors.
AB  - We develop an inference framework for the difference in errors between 2
      prediction procedures. The 2 procedures may differ in any aspect and possibly
      utilize different sets of covariates. We apply training and testing on the same
      data set, which is accommodated by sample splitting. For each split, both
      procedures predict the response of the same samples, which results in paired
      residuals to which a signed-rank test is applied. Multiple splits result in
      multiple p-values. The median p-value and the mean inverse normal transformed p
      value are proposed as summary (test) statistics, for which bounds on the overall
      type I error rate under a variety of assumptions are proven. A simulation study
      is performed to check type I error control of the least conservative bound.
      Moreover, it confirms superior power of our method with respect to a one-split
      approach. Our inference framework is applied to genomic survival data sets to
      study 2 issues: compare lasso and ridge regression and decide upon use of both
      methylation and gene expression markers or the latter only. The framework easily
      accommodates any prediction paradigm and allows comparing any 2, possibly
      nonmodel-based, prediction procedures.

PMID- 19380518
TI  - What exactly are the benefits of stimulants for ADHD?

PMID- 19380519
TI  - A pilot study of working memory and academic achievement in college students with
      ADHD.
AB  - OBJECTIVE: To investigate working memory (WM), academic achievement, and their
      relationship in university students with attention-deficit/hyperactivity disorder
      (ADHD). METHOD: Participants were university students with previously confirmed
      diagnoses of ADHD (n = 16) and normal control (NC) students (n = 30).
      Participants completed 3 auditory-verbal WM measures, 2 visual-spatial WM
      measures, and 1 control executive function task. Also, they self-reported grade
      point averages (GPAs) based on university courses. RESULTS: The ADHD group
      displayed significant weaknesses on auditory-verbal WM tasks and 1 visual-spatial
      task. They also showed a nonsignificant trend for lower GPAs. Within the entire
      sample, there was a significant relationship between GPA and auditory-verbal WM.
      CONCLUSION: WM impairments are evident in a subgroup of the ADHD population
      attending university. WM abilities are linked with, and thus may compromise,
      academic attainment. Parents and physicians are advised to counsel university
      bound students with ADHD to contact the university accessibility services to
      provide them with academic guidance.

PMID- 19380521
TI  - Combined inhibition of MET and EGFR suppresses proliferation of malignant
      mesothelioma cells.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive neoplasm associated with
      asbestos exposure. Although expression and activation of receptor tyrosine
      kinases (RTKs), including MET, have been reported in most MPM, specific RTK
      inhibitors showed less than the expected response in MPM cells. To determine
      whether the lack of response of MET inhibitors was due to cooperation with other
      RTKs, we determined activation status of MET and other RTKs, including epidermal
      growth factor receptor (EGFR) family of 20 MPM cell lines, and tested whether
      dual RTK inhibition is an effective therapeutic strategy. We detected MET
      upregulation and phosphorylation (thus indicating activation) in 14 (70%) and 13
      (65%) cell lines, but treatment with MET-specific inhibitors showed weak or
      modest effect of suppression in most of the cell lines. Phospho-RTK array
      analysis revealed that MET was simultaneously activated with other RTKs,
      including EGFR, ErbB2, ErbB3 and platelet-derived growth factor receptor-beta.
      Combination of MET and EGFR inhibitors triggered stronger inhibition on cell
      proliferation and invasion of MPM cells than that of each in vitro. These results
      indicated that coactivation of RTKs was essential in mesothelioma cell
      proliferation and/or survival, thus suggesting that simultaneous inhibition of
      RTKs may be a more effective strategy for the development of molecular target
      therapy for MPM.

PMID- 19380520
TI  - Endocrine dysfunction in p27Kip1 deficient mice and susceptibility to Wnt-1
      driven breast cancer.
AB  - The cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) (p27) is a marker of
      prognosis in many cancers, including breast cancer. Low p27 expression correlates
      with poor prognosis, especially in hormone receptor positive breast tumors. This
      association suggests a role for p27 in hormone-dependent cancer. We used the Wnt
      1 transgenic mouse model to further explore the role of p27 in hormone-driven
      breast cancer. We found that p27 deficiency did not alter breast cancer rate in
      either male or female Wnt-1 mice. However, we did find p27-/- females had reduced
      levels of serum progesterone (P) and increased variability in estradiol (E),
      which could have affected their cancer susceptibility. To equalize hormone
      levels, an additional cohort of Wnt-1 female mice was ovariectomized and
      implanted with slow release pellets of E and P. Although this treatment did not
      alter the breast cancer rate, it did accelerate the development of pituitary and
      gastric tumors in p27-/- mice. This study shows that while not a significant
      inhibitor of Wnt-1-driven breast cancer, p27 inhibits gastric tumors, whose
      latency is modulated by sex steroids.

PMID- 19380522
TI  - A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with
      reduced survival in oral cancers.
AB  - MicroRNA (miRNA)-binding site polymorphisms that could contribute to disease risk
      and prognosis are rapidly being identified and investigated as this genetic
      variation may have a potentially profound impact on human health. A recently
      described variant allele in the KRAS 3' untranslated region that arises in the
      let-7 miRNA complementary site (KRAS-LCS6) and leads to increased KRAS expression
      in lung cancer was examined for its association with the occurrence of head and
      neck squamous cell carcinoma (HNSCC). We examined the prevalence of the KRAS-LCS6
      variant allele in a population-based case-control study of HNSCC to determine if
      this KRAS-LCS6 genotype was associated with disease occurrence and patient
      survival. Although the KRAS-LCS6 variant genotype was not associated with the
      overall risk of HNSCC, cases with the KRAS-LCS6 variant genotype had
      significantly reduced survival [hazard ratio (HR), 1.6; 95% confidence interval
      (CI), 1.0-2.5] in models controlled for confounders of survival. This risk was
      greatest in cases of oral cavity carcinoma (HR, 2.7; 95% CI, 1.4-5.3). These data
      demonstrate that cases with the KRAS-LCS6 variant have significantly reduced
      survival time and suggest that this variant may alter the phenotype or
      therapeutic response of this disease.

PMID- 19380524
TI  - MR voiding cystography for evaluation of vesicoureteral reflux.
AB  - OBJECTIVE: The purpose of our study is to present a real-time interactive
      continuous fluoroscopy MRI technique for vesicoureteral reflux (VUR) diagnosis.
      CONCLUSION: MR voiding cystography with a real-time interactive MR fluoroscopic
      technique on an open MRI magnet is feasible for the evaluation of VUR in
      children.

PMID- 19380525
TI  - Cardiac cysticercosis.

PMID- 19380523
TI  - Computer-assisted ultrasound analysis of liver echogenicity in obese and normal
      weight children.
AB  - OBJECTIVE: No simple computer-assisted method for assessing liver echogenicity
      has been developed to date. This study describes an accessible and reproducible
      computer-assisted method for measuring liver echogenicity in obese (body mass
      index [BMI] >/= 97th percentile) and normal-weight (BMI from 25th to 75th
      percentile) children and correlates the results with laboratory test results.
      SUBJECTS AND METHODS: Twenty-two children (age range, 6-11 years) were assigned
      to one of two groups of 11 children each and paired by sex and age. All children
      underwent ultrasound, anthropometric measurements, and laboratory tests. A
      hepatorenal index was calculated using software to analyze the difference in
      echogenicity between the liver parenchyma and kidney cortex. The Student's t test
      and Mann-Whitney U test were used for statistical analyses. RESULTS: The
      hepatorenal index was statistically different between the obese and normal-weight
      children (33.9 +/- 6.6 vs 14.1 +/- 6.1, p < 0.001). The analysis of laboratory
      tests of obese and normal-weight children revealed statistically significant
      differences in the values of glucose (p = 0.034), insulin (p = 0.008),
      triglycerides (p = 0.036), uric acid (p < 0.001), and alkaline phosphatase (p =
      0.045). CONCLUSION: Computer-assisted analysis of ultrasound liver echogenicity
      using the software is an accessible, reproducible, and easy-to-use diagnostic
      tool for calculating the hepatorenal index. This tool may be used for follow-up
      and control in the treatment of fat infiltration in the liver of obese children.

PMID- 19380526
TI  - IV contrast infusion for coronary artery CT angiography: literature review and
      results of a nationwide survey.
AB  - OBJECTIVE: The purpose of our study was to review investigations that evaluated
      contrast infusion using MDCT with submillimeter detector configuration for
      coronary artery CT angiography (CTA). Published data are supplemented with 2006
      survey results from centers practicing 64-MDCT coronary artery angiography.
      CONCLUSION: Literature and survey results suggest a consensus for the use of IV
      contrast volumes < 100 mL, infusion rate of 5 mL/s, and a saline chaser. A range
      of concentrations can be used to attain target coronary artery attenuation
      levels.

PMID- 19380527
TI  - Aortic diameter, true lumen, and false lumen growth rates in chronic type B
      aortic dissection.
AB  - OBJECTIVE: The objective of this study was to evaluate growth rates of the aorta,
      true lumen, and false lumen in chronic type B aortic dissections. MATERIALS AND
      METHODS: Nineteen consecutive patients with acute type B aortic dissection
      treated medically between 2000 and 2006 were followed with serial MDCT
      angiography and MR angiography scans during the chronic phase (mean, 5.3 scans
      per patient; mean follow-up, 17.9 months). Aortic diameter, true lumen diameter,
      true lumen area, false lumen diameter, and false lumen area were measured at
      baseline and at each subsequent follow-up study using 3D workstations. Growth
      rates were assessed with linear regression analyses. RESULTS: One hundred scans
      were analyzed. The maximum aortic diameter increased significantly over time at a
      mean rate of 7.1 mm/y (p = 0.004). False lumen diameter (mean, 6.5 mm/y; p =
      0.011), false lumen area (5.35 cm(2)/y, p = 0.013), true lumen diameter (0.79
      mm/y, p = 0.01), and logarithm true lumen area (0.13 cm(2)/y, p = 0.02) all
      increased significantly over time, with greater increases in the size of the
      false lumen than the true lumen. The overall aortic diameter growth rate was
      significantly higher in patients who ultimately underwent aortic repair or died
      (15.4 mm/y) than in patients who did not undergo an intervention (1.8 mm/y, p =
      0.008). CONCLUSION: Maximum aortic diameter in type B dissections increases
      significantly over time, primarily because of the increasing size of the false
      lumen. Patients with high aortic diameter growth rates are more likely to require
      endovascular or open surgical aortic repair during the chronic phase.

PMID- 19380528
TI  - CT hypotension complex (shock bowel) is not always due to traumatic hypovolemic
      shock.
AB  - OBJECTIVE: The purpose of our study was to review the clinical and CT findings in
      a substantial series of 41 patients with the shock bowel sign to determine if
      there is an association between shock bowel (and other CT signs of hypotension)
      and conditions other than post-traumatic hypovolemic shock. CONCLUSION: The shock
      bowel sign and the CT hypotension complex are frequently associated with
      hypotension from causes other than trauma-induced hypovolemic shock, such as
      severe head or spine injury, cardiac arrest, septic shock, bacterial
      endocarditis, and diabetic ketoacidosis. Other elements of the CT hypotension
      complex such as flattening of the inferior vena cava and aorta, abnormal
      pancreatic enhancement and peripancreatic fluid, and hypoperfusion of the spleen
      and liver are variably associated with shock bowel whether due to posttraumatic
      hypovolemia or other causes of hypotension. The CT hypotension complex (shock
      bowel) has important prognostic and therapeutic implications and can probably be
      distinguished from bowel trauma and other forms of bowel injury in most cases.

PMID- 19380529
TI  - Sclerosing angiomatoid nodular transformation.

PMID- 19380530
TI  - Errare humanum est: frequency of laterality errors in radiology reports.
AB  - OBJECTIVE: The purpose of our study was to determine the frequency of
      discrepancies in side of findings (side discrepancies) in the body and the
      impression sections of radiology reports. In addition, we determined the
      frequency of corrected side discrepancies between radiology reports and images in
      a larger database of radiology reports. MATERIALS AND METHODS: In this cross
      sectional study, all radiology reports from January 1, 2007, through December 31,
      2007 (n = 1,065,322), that had an addendum were assessed using a radiology
      reports search engine and searching for the words "left," "right," and "addendum"
      to locate laterality errors between the body of the report and the impression
      section. For reports with discrepancies, we recorded the patient's sex, true side
      of the lesion, and the imaging technique. All reports with an addendum (n =
      13,821) in January 2007 containing the words "left" and "right" were evaluated
      using the same search engine for similar discrepancies. Imaging studies of
      reports with errors were reviewed to determine the correct side of the lesion and
      the clinical significance of the errors. RESULTS: Of the 1,065,322 reports, 88
      side discrepancies were reported in addenda. The errors in mislabeling the side
      of the lesion were more common in female (n = 58) than in male (n = 30) patients.
      Of the 88 errors reported in addenda, 27 were labeled incorrectly in the body of
      the report, 29 in the impression section, and 32 in both the body and impression
      sections. In January 2007, 36 of 13,821 (0.26%) reports had no correction for
      mislabeling of side. Most errors (70.9%) were graded as clinically important.
      CONCLUSION: Clinically significant errors were found in reporting the body side
      of the lesion in radiology reports between the body and impression sections.

PMID- 19380531
TI  - Comprehensive evaluation of patients with suspected renal hypertension using
      MDCT: from protocol to interpretation.
AB  - OBJECTIVE: The objectives of this article are to, first, describe the reasons for
      and details of the MDCT protocol for patients with suspected renal hypertension;
      second, explain the importance of comprehensive evaluation by MDCT in patients
      with suspected renal hypertension; third, review the image appearances of
      important conditions that may be encountered in the reader's clinical practice;
      and, fourth, explain what information should be included in a comprehensive MDCT
      report for patients with suspected renal hypertension. CONCLUSION: MDCT is widely
      used for renal artery evaluation in patients with resistant hypertension. Because
      the regions outside the renal arteries might also have diseases that contribute
      to the symptoms, a comprehensive interpretation including the renal arteries,
      renal parenchyma, adrenal glands, and scanned abdomen is very important. The
      scanning parameters should be adjusted according to the patient's body habitus
      because some patients with suspected renal hypertension are children or young
      women. In this article, cases with illustrations showing the process from
      protocol to interpretation are provided.

PMID- 19380532
TI  - Centerline analysis of aortic CT angiographic examinations: benefits and
      limitations.
AB  - OBJECTIVE: The purpose of our study was to illustrate workflow, benefits, and
      limitations of centerline analysis compared with double oblique multiplanar
      reformations using aortic CT angiography data. CONCLUSION: Semiautomatic
      centerline analysis is beneficial for the assessment of aortic geometry and
      allows precise measurements of aortic diameters and lengths. It can be simple,
      fast, and reproducible, but it should be used with care considering its inherent
      limitations. Manually adjusted multiplanar reformations remain an essential tool
      for intuitive visualization of the vascular anatomy.

PMID- 19380533
TI  - Collateral transformation of the hepatic artery after liver transplantation:
      significance of the tardus-parvus waveform.

PMID- 19380534
TI  - Unenhanced CT in patients with chronic renal failure with clinical suspicion of
      small-bowel infarct.

PMID- 19380535
TI  - Disappearing colonic diverticulosis.

PMID- 19380536
TI  - Excision of high-risk breast lesions on needle biopsy: is there a standard of
      core?

PMID- 19380537
TI  - AJR special issue on pediatric radiology.

PMID- 19380538
TI  - Image Gently Vendor Summit: working together for better estimates of pediatric
      radiation dose from CT.
AB  - OBJECTIVE: Medical physicists currently use two standardized phantoms to estimate
      CT patient radiation dose. This "one-size-fits-all" adult model results in
      underestimates of displayed pediatric CT radiation dose on the console of current
      CT scanners. The purpose of this article is to discuss the Alliance for Radiation
      Safety in Pediatric Imaging Vendor Summit. CONCLUSION: Stakeholders were invited
      to discuss the development of better estimates of pediatric patient radiation
      dose. These stakeholders agreed to partner to improve CT radiation dose estimates
      for children.

PMID- 19380539
TI  - Image Gently: why we should talk to parents about CT in children.

PMID- 19380540
TI  - Imaging children with abdominal trauma.
AB  - OBJECTIVE: Trauma is a leading cause of morbidity and mortality in children. The
      abdomen is the second most common site of injury. This article discusses
      abdominal trauma in children. CONCLUSION: The clinical evaluation of children
      with potential blunt abdominal injury presents a challenging task. Therefore,
      imaging plays an essential role in the evaluation of such children.

PMID- 19380542
TI  - Vesicoureteral reflux and urinary tract infection: evolving practices and current
      controversies in pediatric imaging.
AB  - OBJECTIVE: Pediatric patients with urinary tract infection (UTI) undergo imaging
      tests to detect vesicoureteral reflux (VUR) in the belief that VUR correlates to
      risk of renal scarring. This article describes recent evolution and controversies
      in the management of UTI and VUR. CONCLUSION: Multitechnique imaging of UTI and
      VUR is complex and controversial. Evolution in practice patterns is motivated by
      the desire to rationally minimize unnecessary interventions and radiation
      exposure. Ongoing evidence-based research is needed to further improve practice
      guidelines.

PMID- 19380543
TI  - Evidence-based outcomes of studies addressing diagnostic accuracy of MRI of
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: Our objective was to semiquantitatively evaluate the diagnostic
      accuracy of MRI for evaluation of synovium and cartilage of peripheral joints in
      juvenile idiopathic arthritis (JIA) according to the levels of evidence and
      recommendations of the Canadian Task Force on Periodic Health Examination
      guidelines. CONCLUSION: Articles were screened using MEDLINE, EMBASE, DARE, and
      the Cochrane Library. Two independent reviewers assessed whether the currently
      available MRI techniques are accurate for diagnosis of synovial hypertrophy and
      cartilage degeneration in children with JIA. Overall, there is fair (grade B)
      strength of evidence that MRI is an accurate diagnostic method for evaluating
      synovium and cartilage and for assessing clinical responsiveness to treatment in
      peripheral joints in JIA.

PMID- 19380541
TI  - Language networks in children: evidence from functional MRI studies.
AB  - OBJECTIVE: The purpose of our study was to review functional MRI and other
      neuroimaging studies of language skills in children from infancy to adulthood.
      CONCLUSION: Functional MRI (fMRI) and other neuroimaging studies show
      developmental changes in the networks of brain regions supporting language, which
      can be affected by brain injuries or neurologic disorders. Particular aspects of
      language rely on networks that lateralize to the dominant hemisphere; others rely
      on bilateral or nondominant mechanisms. Multiple fMRI tasks for pediatric
      patients characterize functional brain reorganization that may accompany language
      deficits.

PMID- 19380544
TI  - Role of CT in the evaluation of congenital cardiovascular disease in children.
AB  - OBJECTIVE: The purpose of this review is to describe the role of CT in the
      evaluation of congenital cardiovascular disease in children. Clinical
      indications, imaging techniques, and illustrations of relevant conditions are
      presented. CONCLUSION: CT accurately depicts many forms of congenital
      cardiovascular disease in children. It is particularly valuable in the assessment
      of extracardiac vascular anomalies and in the evaluation of postoperative
      complications.

PMID- 19380545
TI  - Diagnosis of osteomyelitis in children: utility of fat-suppressed contrast
      enhanced MRI.
AB  - OBJECTIVE: The purpose of this study was to determine whether the use of fat
      suppressed contrast-enhanced MRI, compared with unenhanced MRI alone, increases
      reader confidence in the diagnosis of osteomyelitis and its complications in
      children. MATERIALS AND METHODS: MRI studies of 78 skeletally immature children
      and adolescents (median age, 3.6 years) with suspected nonspinal osteomyelitis
      were reviewed in consensus by two readers. Unenhanced images were evaluated first
      and then contrast-enhanced MR images. Images were scored for the presence or
      absence of osteomyelitis, abscess, septic arthritis, and physeal involvement on a
      5-point scale ranging from definitely absent to definitely present. Forty-two
      additional studies were evaluated to test interobserver agreement. RESULTS:
      Osteomyelitis was clinically diagnosed in 40 cases (51%). There was no
      significant difference between the sensitivity and specificity of unenhanced MRI
      (p = 1.0) and those of contrast-enhanced MRI (p = 0.77) for the diagnosis of
      osteomyelitis. Nonetheless, there was a significant (p < 0.001) increase in
      confidence in the diagnosis of osteomyelitis and its complications. This increase
      in confidence was most pronounced for the diagnosis of abscess (46%). The
      addition of contrast enhancement was least useful in findings deemed definitely
      absent on unenhanced MR images. CONCLUSION: Although it does not increase the
      sensitivity or specificity of the diagnosis, use of contrast-enhanced MRI does
      increase reader confidence in the diagnosis of osteomyelitis and its
      complications in cases in which bone or soft-tissue edema is found on unenhanced
      images. In the clear absence of edema on unenhanced images, however, contrast
      enhancement is not needed.

PMID- 19380546
TI  - MR small-bowel follow-through for investigation of suspected pediatric small
      bowel pathology.
AB  - OBJECTIVE: The purpose of our study was to evaluate the potential role of an MR
      small-bowel follow-through (SBFT) technique in the investigation of suspected
      pediatric small-bowel abnormalities. MATERIALS AND METHODS: Between September
      2003 and January 2008, 280 MR SBFT examinations were performed for investigation
      of known or suspected small-bowel abnormalities, including 19 of 280 examinations
      in 17 children (mean age, 13 years; age range 6-17 years), representing the
      current study population. A standardized technique was used in all cases,
      including axial and coronal steady-state free precession acquisitions at
      successive time intervals until completion. Retrospective analysis of the studies
      obtained was performed by two radiologists, who blindly and independently scored
      predefined small-bowel segments according to the degree of luminal distention
      achieved. Any pathologic lesions detected were also noted. Indicators of
      examination success as a whole (volume, tolerability, and side effects of oral
      contrast material) were also noted, as were details pertaining to examination
      duration (number of visits to the MR table, total table time). RESULTS: Oral
      contrast medium was ingested and subsequent imaging was possible in all patients;
      84.2% of patients tolerated the oral contrast material well and 15.8% showed
      moderate tolerance. The MR table time ranged from 2 to 4 minutes, without early
      termination of the examination in any case. The average number of visits to the
      MR table was 1.3 (range, 1-3). The mean duration for complete small-bowel
      evaluation was 25 minutes (range, 20-60 minutes). The mean distention scores were
      well within the diagnostic range in all small-bowel segments for both observers,
      with a substantial degree of interobserver agreement in score assignment (kappa =
      0.73). Pathologic lesions were identified in 53% of studies. CONCLUSION: MR SBFT
      represents a promising, and perhaps optimal, technique for pediatric small-bowel
      evaluation for a variety of reasons, including its high tolerability, lack of
      ionizing radiation, avoidance of duodenojejunal intubation, and excellent luminal
      distention achieved. Furthermore, this technique allows "pseudodynamic"
      functional imaging while also showing extraluminal disease, without known
      biologic risk.

PMID- 19380547
TI  - MDCT pulmonary angiography evaluation of pulmonary embolism in children.
AB  - OBJECTIVE: The purpose of our study was to determine the prevalence and anatomic
      distribution of pulmonary embolism (PE) in a group of consecutive pediatric
      patients with clinically suspected PE using MDCT pulmonary angiography (pulmonary
      CTA). MATERIALS AND METHODS: We used our hospital information system to
      retrospectively identify all consecutive pediatric patients (< 18 years of age)
      with clinically suspected PE who underwent pulmonary CTA from July 2004 to August
      2007. Two experienced pediatric radiologists retrospectively reviewed by
      consensus a series of 98 consecutive pulmonary CTA studies. Each examination was
      reviewed for the ability to visualize pulmonary arteries and the presence of PE.
      For positive cases, the level of involvement was classified as central, lobar,
      segmental, or subsegmental. Lobar location was also recorded using standard
      nomenclature. Pulmonary CTA results were compared with the results of lower
      extremity ultrasound studies in the subset of patients who underwent both
      procedures. RESULTS: The study population consisted of 84 children who underwent
      a total of 98 pulmonary CTA studies. All pulmonary CTA studies were technically
      successful in visualizing arteries to the level of segmental pulmonary arteries,
      but the evaluation of subsegmental pulmonary arteries was limited in 78 (80%)
      examinations. Thirteen (15.5%) of 84 children were found to have PE on pulmonary
      CTA. PE was localized in the lobar pulmonary artery in 12 (39%), the segmental
      pulmonary artery in 11 (35%), the subsegmental pulmonary artery in five (16%),
      and the main or central pulmonary artery in three (10%) patients. PE was
      distributed in the right lower lobe in 12 (37%), the left lower lobe in eight
      (24%), the right upper lobe in five (15%), the right middle lobe in four (12%),
      and the left upper lobe in four (12%) patients. Ten of 13 patients with PE
      underwent lower extremity Doppler ultrasound, of whom one (10%) was positive for
      deep venous thrombosis. CONCLUSION: The prevalence of PE may be more common among
      pediatric patients than previously reported and has a similar distribution to
      that in adult patients.

PMID- 19380548
TI  - Imaging in pediatric urinary tract infection: a 9-year local experience.
AB  - OBJECTIVE: Urinary tract infection (UTI) is a common disease entity in children,
      and a number of imaging options are offered for these patients. The purpose of
      our study was to retrospectively describe the (99m)Tc-labeled dimer captosuccinic
      acid (DMSA) renal scintigraphy, ultrasound, and micturating cystourethrography
      (MCU) findings over a 9-year period. MATERIALS AND METHODS: All children younger
      than 10 years old who presented to a local hospital in Hong Kong between July 1,
      1997, and June 30, 2006, with culture-confirmed UTI and who subsequently
      underwent DMSA scintigraphy, ultrasound, and MCU were identified. For the purpose
      of this study, patients with underlying major congenital urinary tract
      abnormalities were excluded. DMSA scintigraphy was regarded as the gold standard
      for the diagnosis of renal scarring. DMSA scintigraphy, ultrasound, and MCU
      findings and clinical outcomes were reviewed and analyzed. RESULTS: A total of
      583 children were included in the study. Of these, 432 children (74.1%) had
      normal findings on ultrasound and on MCU. Only 13 children (3%) of this group had
      renal scarring as shown on DMSA scintigraphy. The overall negative predictive
      value (NPV) for excluding renal scarring of combined ultrasound and MCU reached
      97%. The NPV was 97.7% in the subgroup of patients 0 to 2 years old. CONCLUSION:
      For children younger than 2 years with UTI in the absence of underlying major
      congenital urinary tract abnormalities, we recommend that DMSA scintigraphy may
      be withheld if findings on both ultrasound and MCU examinations are normal.

PMID- 19380549
TI  - Radiologist-supervised ketamine sedation for solid organ biopsies in children and
      adolescents.
AB  - OBJECTIVE: Pediatric interventional radiologists are frequently challenged when
      faced with organ biopsies. Because of the need for patient immobility and the
      potential risk of morbidity with patient movement during biopsies, many
      radiologists prefer general anesthesia to sedation. We present our experience
      with radiologist-supervised ketamine sedation in pediatric patients undergoing
      renal and hepatic biopsies. MATERIALS AND METHODS: Quality assurance data were
      accessed from a computerized database that prospectively collects demographics,
      outcome parameters, and adverse events on all patients who receive ketamine
      sedation. Patients received an IV ketamine bolus of 2 mg/kg followed by a
      continuous infusion of ketamine of up to 150 mcg/kg/min titrated to the
      responsiveness of the patient. RESULTS: Sixty-five children received ketamine for
      liver (n = 35) and renal (n = 30) biopsies. The mean age of the study group was
      7.0 +/- 2.7 (SD) years. The cohort included patients with an American Society of
      Anesthesiologists (ASA) physical status classification of ASA 1 (3%), ASA 2
      (78%), and ASA 3 (19%). The duration of ketamine sedation averaged 39 +/- 20 (SD)
      minutes, with an average procedure time of 32 +/- 19 (SD) minutes. All procedures
      were successfully completed, and there were no major adverse events. CONCLUSION:
      Interventional radiologists performing solid organ biopsies in the pediatric
      population often use general anesthesia to ensure immobility, adequate analgesia,
      and safe conditions. Our experience suggests that interventional radiologists may
      supervise a nurse-administered ketamine protocol to provide safe, effective
      analgesia and sedation for liver and renal biopsies.

PMID- 19380550
TI  - Metaphyseal fragmentation with physiologic bowing: a finding not to be confused
      with the classic metaphyseal lesion.
AB  - OBJECTIVE: The purpose of this study was to describe the varied appearances of
      metaphyseal fragmentation associated with physiologic bowing and to estimate
      their frequency in children undergoing radiographic evaluation. CONCLUSION: The
      results of this study suggest that metaphyseal fragmentation is occasionally
      encountered in children with physiologic bowing. Results of a systematic imaging
      assessment should minimize confusion of this innocent radiologic alteration with
      the classic metaphyseal lesion of child abuse.

PMID- 19380551
TI  - Neonatal malrotation with midgut volvulus mimicking duodenal atresia.
AB  - OBJECTIVE: The purpose of this study was to describe the clinical, imaging, and
      surgical findings in the cases of four neonates with radiographic findings
      suggesting duodenal atresia (double-bubble sign) who were subsequently found to
      have malrotation with midgut volvulus. CONCLUSION: When the surgical treatment of
      a patient with the double-bubble sign is to be delayed, an upper gastrointestinal
      radiographic or ultrasound study is needed to evaluate for malrotation with
      midgut volvulus.

PMID- 19380552
TI  - Imaging of pulmonary venous developmental anomalies.
AB  - OBJECTIVE: The purpose of this article is to review pulmonary venous embryology
      and to present the imaging findings of a variety of pulmonary venous
      developmental anomalies, including total anomalous pulmonary venous connection,
      partial anomalous pulmonary venous connection, pulmonary vein stenosis and
      hypoplasia/atresia, and cor triatriatum. CONCLUSION: There are numerous
      developmental pulmonary venous anomalies. Although these conditions have
      traditionally been evaluated with echocardiography and angiography, they can be
      accurately diagnosed using both MRI and MDCT.

PMID- 19380554
TI  - Pediatric CT radiation dose: how low can you go?
AB  - OBJECTIVE: There is a known risk from radiation. The objective of this article is
      to answer the following question regarding CT: Is there a risk of lowering the
      radiation exposure so low that the risk of missing a diagnosis from excessive
      noise in the image begins to exceed the risk of the radiation itself? CONCLUSION:
      When performing CT, adequate radiation dose must be used to make a confident and
      accurate diagnosis. The total population radiation exposure can be reduced
      effectively by numerous other means, including aggressively reducing the number
      of CT examinations performed for poor clinical indications, scanning only the
      anatomic region of interest, and not performing both unenhanced and contrast
      enhanced scanning unless absolutely necessary.

PMID- 19380553
TI  - Pain in the butt: spectrum of gluteal region abnormalities in children.
AB  - OBJECTIVE: The purpose of this study was to illustrate the spectrum of solitary
      gluteal lesions in children. The distinctive anatomic and radiologic features are
      discussed. CONCLUSION: Pathologic entities in the gluteal region reflect the
      diversity of tissue types present. Ultrasound is valuable for imaging of infants
      and young children and for evaluating superficial lesions. Cross-sectional
      imaging is most useful for defining the extent of disease and may show
      pathognomonic features, enabling a precise diagnosis.

PMID- 19380555
TI  - Childhood Burkitt lymphoma: abdominal and pelvic imaging findings.
AB  - OBJECTIVE: Burkitt lymphoma in children can be localized or disseminated and can
      involve various sites. Our objective is to review the clinical presentation and
      abdominopelvic imaging findings of Burkitt lymphoma in the pediatric population.
      CONCLUSION: Numerous abdominal and pelvic imaging findings are seen in Burkitt
      lymphoma affecting the gastrointestinal tract and solid organs. Recognition of
      the common and uncommon imaging findings is essential in the diagnosis and
      treatment of patients with Burkitt lymphoma because prompt therapy is critical.

PMID- 19380556
TI  - Do emergency physicians use serum D-dimer effectively to determine the need for
      CT when evaluating patients for pulmonary embolism? Review of 5,344 consecutive
      patients.
AB  - OBJECTIVE: The purpose of our study was to investigate whether D-dimer screening
      is being used effectively to determine the need for MDCT in diagnosing acute
      pulmonary embolism (PE) in emergency department patients. MATERIALS AND METHODS:
      We performed a retrospective review of all patients who underwent D-dimer testing
      or MDCT in the emergency department from January 1, 2003, through October 31,
      2005. A D-dimer value of > 0.43 microg/mL was considered positive. Diagnosis of
      PE was made on the basis of the MDCT. Clinical algorithms for diagnosing PE
      mandate that patients with a low clinical suspicion for PE undergo D-dimer
      testing, then MDCT if positive. For patients with a high clinical suspicion for
      PE, MDCT should be performed without D-dimer testing. RESULTS: Of 3,716 D-dimer
      tests, 1,431 (39%) were positive and 2,285 (61%) were negative. MDCT was
      performed in 166 (7%) patients with negative D-dimer results and in 826 (58%)
      patients with positive D-dimer results. The prevalence of PE in patients with a
      high clinical suspicion and no D-dimer testing was 9% (139/1,628), which was
      higher than the rate of PE in the positive D-dimer group at 2% (19/826) (p <
      0.0001). There was no significant difference in the prevalence of PE in the
      positive and negative D-dimer groups (2% vs 0.6%, respectively) (p = 0.23). The
      sensitivity and negative predictive value of D-dimer for PE were 95% (95% CI,
      73.1-99.7%) and 99% (95% CI, 96.2-99.9%), respectively. CONCLUSION: D-dimer
      screening is not used according to established diagnostic algorithms to determine
      the need for MDCT in diagnosing acute pulmonary embolism in our emergency
      department.

PMID- 19380557
TI  - Effect of slab thickness on the CT detection of pulmonary nodules: use of sliding
      thin-slab maximum intensity projection and volume rendering.
AB  - OBJECTIVE: The objective of this study was to evaluate the detection rates of
      pulmonary nodules on CT as a function of slab thickness using sliding thin-slab
      maximum intensity projection (MIP) and volume rendering (VR). SUBJECTS AND
      METHODS: Eighty-eight oncology patients (33 women, 55 men; mean age, 59 years;
      age range, 18-81 years) who routinely underwent chest CT examinations were
      prospectively included. Two radiologists independently evaluated each CT
      examination for the presence of pulmonary nodules using MIP and VR, with each
      image reconstructed using three different slab thicknesses (5, 8, 11 mm). The
      standard of reference was the maximum number of detected nodules, which were
      classified by localization and size, judged to be true-positives by a consensus
      panel. Interreader agreement was assessed by kappa value on a nodule-by-nodule
      basis. Sensitivities for both reconstruction techniques and for the three slab
      thicknesses were calculated using the proportion procedure for survey data with
      the patient as the primary sample unit and were compared using the Wilcoxon's
      signed rank test with Bonferroni correction for both readers separately. RESULTS:
      One thousand fifty-eight true-positive nodules were detected. Interreader
      agreement was fair to moderate. Sensitivity for pulmonary nodules was superior
      for 8-mm MIP (reader 1, 84%; reader 2, 81%) and was significantly better than the
      sensitivities of all other tested techniques for both readers (p < 0.001 each)
      independent of nodule localization and size (except for one reader's analysis of
      8-mm MIP versus 11-mm MIP for nodules > 8 mm). A higher sensitivity was achieved
      using MIP than VR. CONCLUSION: MIP with a slab thickness of 8 mm is superior in
      the detection of pulmonary nodules to all other tested techniques.

PMID- 19380558
TI  - CT colonography to screen for colorectal cancer and aortic aneurysm in the
      Medicare population: cost-effectiveness analysis.
AB  - OBJECTIVE: CT colonography (CTC) is a recommended test for colorectal cancer
      (CRC) screening according to the updated 2008 American Cancer Society guidelines.
      CTC can also accurately detect abdominal aortic aneurysm (AAA). This
      collaborative gastroenterology-radiology project evaluated the cost-effectiveness
      and clinical efficacy of CTC in the Medicare population. MATERIALS AND METHODS: A
      computerized Markov model simulated the development of CRC and AAA in a
      hypothetical cohort of 100,000 U.S. adults > or = 65 years old. Screening with
      CTC at 5- and 10-year intervals using a 6-mm size threshold for polypectomy was
      compared with primary optical colonoscopy screening every 10 years and with no
      screening. Base case costs for CTC and optical colonoscopy were $674 and $795,
      respectively. The costs of the imaging workup for extracolonic findings at CTC
      were also included. RESULTS: CTC resulted in 7,786 and 7,027 life-years gained at
      5- and 10-year intervals, respectively, compared with 6,032 life-years gained
      with 10-year optical colonoscopy. The increase in overall efficacy with CTC was
      primarily due to prevention of AAA rupture because CRC prevention and CRC
      detection rates were similar for CTC and optical colonoscopy. All three
      strategies were highly cost-effective compared with no screening, with an
      incremental cost-effectiveness ratio (ICER) of $6,088, $1,251, and $1,104 per
      life-year gained for 5-year CTC, 10-year CTC, and 10-year optical colonoscopy
      strategies, respectively. The ICER of 5-year CTC and 10-year CTC versus optical
      colonoscopy was $23,234 and $2,144 per life-year gained, respectively.
      CONCLUSION: Because of its ability to simultaneously screen for both CRC and AAA,
      CTC is a highly cost-effective and clinically efficacious screening strategy for
      the Medicare population.

PMID- 19380559
TI  - Focal confluent fibrosis in cirrhotic liver: natural history studied with serial
      CT.
AB  - OBJECTIVE: The objective of this study was to assess the long-term natural
      history of focal confluent fibrosis in cirrhotic liver with CT. MATERIALS AND
      METHODS: Two radiologists retrospectively reviewed in consensus 118 liver CT
      examinations in 26 patients (19 men, seven women; age range, 32-68 years; mean
      age, 50 years) performed over approximately 6 years. Helical CT scans were
      obtained before and 30-35 and 65-70 seconds after injection of 125-150 mL of
      contrast medium at a rate of 4-5 mL/s. Proof of cirrhosis was based on liver
      transplantation (n = 6), biopsy (n = 9), or imaging findings (n = 11). The
      number, location, and attenuation of fibrotic lesions and presence of trapped
      vessels were evaluated. Variation of hepatic retraction associated with the
      development of focal confluent fibrosis lesions was assessed using the ellipsoid
      volume formula and an arbitrary retraction index. RESULTS: Each radiologist
      identified 41 focal confluent fibrosis lesions. All lesions were identified by
      both radiologists. Twelve patients (46%) had a single lesion, 13 (50%) had two
      lesions, and one (4%) had three lesions. Thirty-four (83%) of 41 lesions were
      located in segment IV, VII, or VIII. Thirty-two lesions (78%) were
      hypoattenuating on unenhanced images, 25 lesions (61%) were hypoattenuating on
      hepatic arterial phase images, and 20 lesions (49%) were isoattenuating on portal
      venous phase images. Seven lesions (17%) were or became hyperattenuating at
      follow-up on portal venous phase images. Trapped vessels were found in six
      lesions (15%). The retraction index showed a significant increase over time (r =
      0.423, p < or = 0.0001). CONCLUSION: The degree of capsule retraction associated
      with focal confluent fibrosis evolves with time and relates to the natural
      evolution of cirrhosis.

PMID- 19380560
TI  - Effects of breath-hold and cardiac cycle on the MRI appearance of the aorta and
      inferior vena cava in t2 abdominal imaging.
AB  - OBJECTIVE: The purpose of this article is to review the MR principles of blood
      signal and normal flow-related phenomena seen in the aorta and inferior vena cava
      (IVC) on T2-weighted images of the abdomen and to discuss the physiologic and
      physical basis of signal alterations with breath-hold imaging. We define time-of
      flight (TOF) loss and list the factors that affect it; explain the physiologic
      effects of breath-hold imaging on both aortic and IVC waveforms and velocity;
      state which abdominal T2 imaging techniques are most susceptible to variable TOF
      effects and explain why based on physiologic effects and MR principles; and
      describe three trouble-shooting techniques to confirm that unexpected signal does
      not reflect pathology. CONCLUSION: T2 images customarily result in TOF loss and
      dark blood signal. Abdominal MRI relies extensively on breath-hold imaging
      techniques that may alter markedly the flow velocity in normal vessels. This
      marked flow change results in signal heterogeneity and variable TOF loss
      especially with faster sequences filling k-space in shorter time frames. Breath
      hold imaging decreases k-space fill time, and of the breath-hold T2 techniques,
      single-shot fast spin-echo decreases k-space fill time the most. Atypical blood
      signal during breath-hold imaging may mimic pathology, but abnormal findings can
      be verified by review of other sequences and planes of imaging.

PMID- 19380561
TI  - Preoperative T staging of urinary bladder cancer: does diffusion-weighted MRI
      have supplementary value?
AB  - OBJECTIVE: The objective of our study was to evaluate whether diffusion-weighted
      MRI has supplementary value in the preoperative T staging of urinary bladder
      cancer. MATERIALS AND METHODS: Nineteen consecutive patients (18 men and one
      woman; age range, 55-83 years; mean, 71 years) known to have or suspected of
      having urinary bladder cancer underwent MRI at our institution. Urinary bladder
      cancer was pathologically proven in 18 patients. The pathologic stages were T1 in
      14 patients, T2 in two, T3 in one, and T4 in one. Three separate MR image sets
      were retrospectively reviewed by two independent radiologists: unenhanced T1
      weighted images (TR/TE, 607/10) and T2-weighted images (TR(eff)/TE(eff),
      4,415/100); unenhanced T1-weighted, T2-weighted, and gadolinium-enhanced images
      (TR/TE, 10/4.2); and unenhanced T1-weighted, T2-weighted, and diffusion-weighted
      images (TR(eff)/TE(eff), 2,191/69; b factor, 1,000 s/mm(2)). The radiologists,
      who were blinded to the pathology findings, assigned T stages and confidence
      levels for tumors of stage T2 or greater. We used pathologic stages documented in
      the official pathologic reports as the standard of reference. Observer
      performance was tested using Spearman's rank correlation, the McNemar test, and
      receiver operating characteristic (ROC) curve analysis. RESULTS: The correlation
      between the radiologic and pathologic stages was greater with the diffusion
      sequence (rho = 0.66) than with the unenhanced (0.62) or gadolinium-enhanced
      (0.62) sequence (p = 0.34). The sensitivity, specificity, accuracy, and area
      under the ROC curve for tumors of stage T2 or greater were 80%, 79%, 79%, and
      0.71 for the unenhanced sequence; 80%, 79%, 79%, and 0.77 for the gadolinium
      sequence; and 40%, 93%, 79%, and 0.56 for the diffusion-weighted sequence,
      respectively (p > 0.05). CONCLUSION: Our results suggest that diffusion-weighted
      MRI might have high specificity for the detection of invasive urinary bladder
      tumors. Patients with suspected urinary bladder carcinomas may well be evaluated
      by MRI including diffusion-weighted imaging for better preoperative T staging.

PMID- 19380562
TI  - Clinical and radiologic features of cystic renal masses.
AB  - OBJECTIVE: The purpose of our study was to review the clinical correlates and
      imaging features of benign and malignant cystic renal masses. CONCLUSION: This
      article reviews the radiologic findings of cystic renal lesions. After completing
      this article, readers should be able to recognize the more common complex cystic
      renal lesions.

PMID- 19380563
TI  - Visibility of radiologists: helping to secure your future.
AB  - OBJECTIVE: The success of imaging services has been driven, in large part, by
      radiologists, who arguably became the most visible physicians within their
      organizations. But this success came at a price, and many groups have sought ways
      to reduce their traditional responsibilities. In doing so, they have given away
      one of their strongest assets, their visibility. They now risk being seen as
      commodities rather than peers--a position that may make them invisible
      altogether. This article addresses ways to improve these issues. CONCLUSION:
      Radiologists need to foster professional relationships with all clinical staff,
      not just physicians. They need to be seen as visible, active, collaborative, and
      positive participants by all members of the organization. In this way, they can
      ensure their visibility and continued demand for their services.

PMID- 19380564
TI  - Computers, conversation, utilization, and commoditization: the 2008 Herbert
      Abrams Lecture.

PMID- 19380565
TI  - Interaction between academic radiology and the news media: a potentially powerful
      and unpredictable process--five stories.
AB  - OBJECTIVE: Although articles have been published describing the relationship
      between news reports and the general medical literature, to our knowledge little
      has been published describing the relationship between radiology publications and
      news coverage. We present five instances of news stories centered on radiology
      publications or abstracts of presentations at national meetings and the effect of
      the media coverage within the medical community. CONCLUSION: The five examples
      show that news coverage can have a dramatic effect on advancing research findings
      and public health information published in radiology journals. Even when news
      coverage is inaccurate or sensationalized, the attention of the general public
      can drive change not only generally in medicine but also specifically in
      radiology.

PMID- 19380566
TI  - Continue drawing back the curtain: educating the community about radiology.

PMID- 19380567
TI  - Extraforaminal with or without foraminal disk herniation: reliable MRI findings.
AB  - OBJECTIVE: The purpose of our study was to evaluate spinal MR images for
      extraforaminal disk herniation with or without foraminal disk herniation to
      determine the reliable MRI findings. MATERIALS AND METHODS: Thirty-five patients
      with extraforaminal with or without foraminal disk herniation confirmed at
      radiculography or surgery between March 2005 and July 2007 underwent spinal MRI.
      We assessed the morphologic features of the disk, changes in nerve root
      thickness, epidural fat obliteration surrounding the nerve root, and displacement
      of the nerve root in the foraminal and extraforaminal zones. RESULTS: Mixed disk
      herniation was found in 23 patients, and purely extraforaminal herniation was
      found in 12 patients. Focal eccentricity of the disk contour was identified in 32
      patients (91%). Change in the nerve root thickness was found in 30 patients
      (86%). The nerve roots were displaced in 22 patients (63%), and the original
      location was maintained in nine patients (26%). Differentiation between the disk
      and the nerve root was poor in four of the 35 patients (11%). Obliteration of the
      epidural fat surrounding the nerve root was present in all patients. CONCLUSION:
      The presence of extraforaminal with or without foraminal disk herniation should
      be ascertained on the basis of the following MRI findings: focal eccentricity of
      the disk contour, obliteration of epidural fat surrounding the nerve root, change
      in the thickness of the nerve root, and displacement of the nerve root.

PMID- 19380568
TI  - Comparison of standard hip MR arthrographic imaging planes and sequences for
      detection of arthroscopically proven labral tear.
AB  - OBJECTIVE: The purpose of this study was to compare multiple imaging planes and
      two pulse sequences for detection of arthroscopically proven labral tears.
      MATERIALS AND METHODS: From March 2004 through June 2007, acetabular labral tear
      was diagnosed at hip arthroscopy of 189 patients. Preoperative MR arthrography of
      the affected hip was performed on 144 patients at our institution. These MR
      arthrograms were retrospectively reviewed by a musculoskeletal fellow and two
      musculoskeletal radiologists. The sequences used were coronal T1-weighted with
      fat saturation, coronal T2-weighted with fat saturation, sagittal T1-weighted
      with fat saturation, axial oblique T1-weighted with fat saturation, sagittal
      oblique T1-weighted with fat saturation, and axial T1-weighted. Using consensus,
      the reviewers evaluated images obtained with each sequence for the presence of a
      tear, number of slices on which a tear was seen, and the signal intensity of the
      tear. RESULTS: Among the 144 tears, 97.2% were identified as definitely present
      on images obtained with at least one of the sequences. The axial oblique sequence
      had the highest individual detection rate (85.0%). The detection rates for the
      sagittal T1-weighted (74.6%), coronal T1-weighted (67.4%), and coronal T2
      weighted (63.6%) sequences were intermediate. Detection rates with the axial T1
      weighted (29.9%) and sagittal oblique (18.2%) sequences were low. With the
      combination of three sequences (coronal T2-weighted with fat saturation, axial
      oblique T1-weighted with fat saturation, and sagittal T1-weighted with fat
      saturation), 95.8% of the 144 tears were identified as definitely present. Twenty
      eight percent of tears had a signal intensity less than that of gadolinium or
      fluid. CONCLUSION: Imaging in the axial oblique plane has the highest rate of
      detection of acetabular labral tears. More than 95% of tears were identified with
      the use of three imaging planes. Signal intensity within a tear does not have to
      be equal to that of gadolinium or fluid to confirm the diagnosis of labral tear.

PMID- 19380569
TI  - Musculocutaneous chronic graft-versus-host disease: MRI follow-up of patients
      undergoing immunosuppressive therapy.
AB  - OBJECTIVE: The purpose of this study was to use MRI and physical examination to
      assess the evolution of disabling musculocutaneous changes induced by chronic
      graft-versus-host disease in patients receiving immunosuppressive therapy.
      CONCLUSION: MRI monitoring appears to yield accurate information about the extent
      and activity of musculocutaneous abnormalities related to chronic graft-versus
      host disease during immunosuppressive therapy.

PMID- 19380570
TI  - Normal appearance and complications of double-bundle and selective-bundle
      anterior cruciate ligament reconstructions using optimal MRI techniques.
AB  - OBJECTIVE: Double-bundle and selective-bundle anterior cruciate ligament (ACL)
      reconstructions are increasingly performed to better reproduce the double-bundle
      anatomy of the native ACL and to improve knee stability and surgical outcomes.
      This article illustrates how to optimize visualization of the ACL bundle anatomy
      and the appearances of graft components and postoperative complications.
      CONCLUSION: It is important for the radiologist to be familiar with the
      appearance of double-bundle and selective-bundle ACL reconstructions and
      associated complications.

PMID- 19380571
TI  - Value of MDCT angiography in developing treatment strategies for critical limb
      ischemia.
AB  - OBJECTIVE: The purpose of this study was to assess the value of MDCT angiography
      in the development of strategies for the treatment of patients with critical limb
      ischemia. MATERIALS AND METHODS: During a 12-month period, 150 patients were
      referred to our department for CT angiography of the peripheral arteries. All
      patients (n = 28) with clinical stage IV peripheral arterial occlusive disease
      were included in this retrospective study. The treatment reports, discharge
      summaries, and follow-up examinations were reviewed to ascertain the number of
      patients correctly treated on the basis of the CT angiographic findings. RESULTS:
      After CT angiography, endovascular treatment was indicated for eight patients,
      surgical revascularization for four patients, and a combined endovascular and
      surgical approach for two patients. That the correct treatment decision had been
      made in all 14 cases was confirmed on the basis of successful endovascular or
      surgical revascularization. In eight patients, medical treatment was indicated,
      and one patient underwent amputation at the level of the thigh. Five patients
      were referred for complementary digital subtraction angiography, but no
      additional findings were made. During follow-up, three of the original 28
      patients were in grave general condition and died within 7 weeks after CT
      angiography. Thirteen patients needed no additional treatment during the follow
      up period through January 2008. After a median treatment-free interval of 381
      days, 12 patients underwent additional revascularization because of clinical
      progression of disease. CONCLUSION: MDCT angiographic findings lead to accurate
      recommendations for the management of critical limb ischemia. Thus CT angiography
      seems to be an important technique for the management of stage IV peripheral
      arterial occlusive disease in patients without absolute contraindications to CT
      angiography.

PMID- 19380572
TI  - Radiofrequency ablation of the spleen in patients with thalassemia intermedia: a
      pilot study.
AB  - OBJECTIVE: We investigated the efficacy and safety of radiofrequency ablation on
      the hematologic parameters in patients with thalassemia intermedia (TI).
      MATERIALS AND METHODS: Radiofrequency ablation of the spleen was performed in 15
      children with TI under general anesthesia using a cool-tip radiofrequency probe.
      These patients were regarded as the radiofrequency ablation group. Nine patients
      with TI who underwent partial splenectomy during the past 3 years and another 14
      patients with TI who underwent total splenectomy were also enrolled in this study
      as the first and second control groups (CG1 and CG2). RESULTS: In the
      radiofrequency ablation group, two (13%) patients showed a significant increase
      in the mean hemoglobin level compared with the year before (1.5 and 1.8 g/dL). In
      addition, three (20%) other patients became transfusion-free in the year after
      radiofrequency ablation. In CG1, one (11%) patient showed a significant increase
      in hemoglobin the year after partial splenectomy, and another two (22%) patients
      became transfusion-free. In CG2, six (43%) patients revealed a significant
      increase in hemoglobin in the year after total splenectomy, and another four
      (29%) revealed a significant decrease in the need for transfusions. The mean
      increase in hemoglobin and platelet count was more significant in CG2 than in the
      radiofrequency ablation group and CG1. The mean hospital stay was significantly
      shorter in the radiofrequency ablation group (1.7 days vs 7.5 and 8.2 days in CG1
      and CG2, respectively). CONCLUSION: We believe that radiofrequency ablation of
      the spleen can be a safe procedure in patients with TI and is at least as
      effective as partial splenectomy, having only minor self-limiting complications.

PMID- 19380573
TI  - Safety and effectiveness of analgesia with remifentanil for percutaneous
      transhepatic biliary drainage.
AB  - OBJECTIVE: The purpose of this study was to evaluate the safety and effectiveness
      of analgesia with remifentanil for percutaneous transhepatic biliary drainage.
      SUBJECTS AND METHODS: Analgesia for percutaneous transhepatic biliary drainage
      was induced with remifentanil in 186 patients over a 1-year period. Remifentanil
      was administered IV with an infusion pump at 0.1 microg/kg/min as the usual dose
      and 0.15 microg/kg/min as the maximal dose. Selected patients with severe anxiety
      also received a 1-mg bolus of midazolam. Vital signs, sedation levels, and side
      effects were checked every 5 minutes during the procedure and recovery. The
      patients scored their pain subjectively on an 11-point numerical rating scale.
      RESULTS: The mean total dose of remifentanil was 116.3 microg (range, 32.5-200
      microg). Midazolam was administered to 15 patients. Transient bradycardia
      occurred in 19 patients (10%). Hypotension did not develop in any patient.
      Respiratory depression occurred in four patients (2%). An appropriate level of
      sedation was obtained in 182 patients (98%), the modified Ramsay score being 2 (n
      = 164, 88%) or 3 (n = 18, 10%). Forty-nine of the patients (26%) indicated no
      pain (numeric rating, 0), 120 (64%) indicated mild pain (numeric rating, 1-3),
      and 16 (9%) indicated moderate pain (numeric rating, 4-6). One patient (1%)
      indicated severe pain (numeric rating, 7). CONCLUSION: Remifentanil is safe and
      highly effective for pain control during percutaneous transhepatic biliary
      drainage. This drug is a suitable option for analgesia during painful
      interventional radiology procedures.

PMID- 19380574
TI  - Role of breast MRI in the preoperative evaluation of patients with newly
      diagnosed breast cancer.
AB  - OBJECTIVE: The purpose of our study was to evaluate in a non-investigational
      setting the effect of preoperative breast MRI on the diagnosis of unsuspected
      additional malignant tumors and on surgical management choices. SUBJECTS AND
      METHODS: One hundred ninety-nine patients with a new diagnosis of breast cancer
      who underwent preoperative bilateral breast MRI were enrolled. Data included
      additional imaging and biopsies performed, final surgical management, and
      pathologic correlation. To reduce bias due to patient preference and variable
      surgical approaches, ipsilateral malignant lesions found on breast MR images were
      retrospectively reviewed by a surgeon blinded to final surgical treatment.
      RESULTS: MRI detected additional suspicious previously unsuspected lesions in 74
      patients (37%). Fifty-four of these lesions, in 38 patients (19%), were
      identified as malignant, of which 41 (76%) were invasive. Retrospective review of
      the MRI-identified ipsilateral malignant lesions resulted in hypothetical
      recommendations that would have altered the surgical treatment of 26 of the
      patients (13%), principally as mastectomy or wider excision. CONCLUSION: For
      patients with a new diagnosis of breast cancer, breast MRI in a mid-sized
      regional hospital depicts unsuspected malignant lesions in both the ipsilateral
      and contralateral breasts in proportions consistent with the results of earlier
      studies at larger institutions. Whether clinical outcome is improved by changes
      in surgical management consequent to MRI detection of unsuspected malignant
      lesions remains unproven.

PMID- 19380575
TI  - Greater transport efficiencies of the membrane fatty acid transporters FAT/CD36
      and FATP4 compared with FABPpm and FATP1 and differential effects on fatty acid
      esterification and oxidation in rat skeletal muscle.
AB  - In selected mammalian tissues, long chain fatty acid transporters (FABPpm,
      FAT/CD36, FATP1, and FATP4) are co-expressed. There is controversy as to whether
      they all function as membrane-bound transporters and whether they channel fatty
      acids to oxidation and/or esterification. Among skeletal muscles, the protein
      expression of FABPpm, FAT/CD36, and FATP4, but not FATP1, correlated highly with
      the capacities for oxidative metabolism (r>or=0.94), fatty acid oxidation
      (r>or=0.88), and triacylglycerol esterification (r>or=0.87). We overexpressed
      independently FABPpm, FAT/CD36, FATP1, and FATP4, within a normal physiologic
      range, in rat skeletal muscle, to determine the effects on fatty acid transport
      and metabolism. Independent overexpression of each fatty acid transporter
      occurred without altering either the expression or plasmalemmal content of other
      fatty acid transporters. All transporters increased fatty acid transport, but
      FAT/CD36 and FATP4 were 2.3- and 1.7-fold more effective than FABPpm and FATP1,
      respectively. Fatty acid transporters failed to alter the rates of fatty acid
      esterification into triacylglycerols. In contrast, all transporters increased the
      rates of long chain fatty acid oxidation, but the effects of FABPpm and FAT/CD36
      were 3-fold greater than for FATP1 and FATP4. Thus, fatty acid transporters
      exhibit different capacities for fatty acid transport and metabolism. In vivo,
      FAT/CD36 and FATP4 are the most effective fatty acid transporters, whereas FABPpm
      and FAT/CD36 are key for stimulating fatty acid oxidation.

PMID- 19380576
TI  - The polypyrimidine tract-binding protein is required for efficient dengue virus
      propagation and associates with the viral replication machinery.
AB  - The polypyrimidine tract-binding protein (PTB) functions primarily as an IRES
      trans-acting factor in the propagation of hepatitis C virus and picornaviruses.
      PTB interacts with secondary structures within the 3'- and 5'-untranslated
      regions of these viral genomes to mediate efficient IRES-mediated viral
      translation. PTB has also been reported to bind to the untranslated region of the
      single-stranded RNA dengue virus (DENV), suggesting a similar function for PTB in
      flaviviruses. Indeed small interfering RNA-mediated PTB knockdown inhibited the
      production of infectious DENV, and this inhibition was specific to PTB knockdown
      and not due to a nonspecific anti-viral state. In fact, PTB depletion did not
      inhibit the production infectious yellow fever virus, another flavivirus.
      Nevertheless, whereas PTB knockdown led to a significant decrease in the
      accumulation of DENV viral RNAs, it did not impair translation. Moreover, PTB was
      shown to interact with the DENV nonstructural 4A protein, a known component of
      the viral replication complex, and with the DENV genome during infection. These
      data suggest that PTB interacts with the replication complex of DENV and is
      acting at the level of viral RNA replication.

PMID- 19380577
TI  - Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains:
      identification of the RNA recognition loop in RIG-I-like receptors.
AB  - The RIG-I like receptor (RLR) comprises three homologues: RIG-I (retinoic acid
      inducible gene I), MDA5 (melanoma differentiation-associated gene 5), and LGP2
      (laboratory of genetics and physiology 2). Each RLR senses different viral
      infections by recognizing replicating viral RNA in the cytoplasm. The RLR
      contains a conserved C-terminal domain (CTD), which is responsible for the
      binding specificity to the viral RNAs, including double-stranded RNA (dsRNA) and
      5'-triphosphated single-stranded RNA (5'ppp-ssRNA). Here, the solution structures
      of the MDA5 and LGP2 CTD domains were solved by NMR and compared with those of
      RIG-I CTD. The CTD domains each have a similar fold and a similar basic surface
      but there is the distinct structural feature of a RNA binding loop; The LGP2 and
      RIG-I CTD domains have a large basic surface, one bank of which is formed by the
      RNA binding loop. MDA5 also has a large basic surface that is extensively flat
      due to open conformation of the RNA binding loop. The NMR chemical shift
      perturbation study showed that dsRNA and 5'ppp-ssRNA are bound to the basic
      surface of LGP2 CTD, whereas dsRNA is bound to the basic surface of MDA5 CTD but
      much more weakly, indicating that the conformation of the RNA binding loop is
      responsible for the sensitivity to dsRNA and 5'ppp-ssRNA. Mutation study of the
      basic surface and the RNA binding loop supports the conclusion from the structure
      studies. Thus, the CTD is responsible for the binding affinity to the viral RNAs.

PMID- 19380578
TI  - Defining contributions of paternally methylated imprinted genes at the Igf2-H19
      and Dlk1-Gtl2 domains to mouse placentation by transcriptomic analysis.
AB  - Parental genome functions in ontogeny are determined by interactions among
      transcripts from the maternal and paternal genomes, which contain many genes
      whose expression is strictly dependent on their parental origin as a result of
      genomic imprinting. Comprehensive recognition of the interactions between
      parental genomes is important for understanding genomic imprinting in mammalian
      development. The placenta is a key organ for exploring the biological
      significance of genomic imprinting. To decipher the unknown roles of paternally
      methylated imprinted genes on chromosomes 7 and 12 in mouse placentation, we
      performed a transcriptomic analysis on placentae in three types of bimaternal
      conceptuses that contained genomes derived from both non-growing and fully grown
      oocytes. Furthermore, we used the Ingenuity pathway analysis software to predict
      key networks and identify functions specific to paternally methylated imprinted
      genes regulated by the Igf2-H19 imprinting control region and Dlk1-Dio3
      imprinting control region. The data suggested that dynamic conversion of the gene
      expression profile by restoring the expression of paternally methylated imprinted
      genes resulted in phenotypic improvements in bimaternal placentae. These results
      provide a framework to further explore the role of epigenetic modifications in
      paternal genome during mouse placentation.

PMID- 19380579
TI  - The isomerase active site of cyclophilin A is critical for hepatitis C virus
      replication.
AB  - Cyclosporine A and nonimmunosuppressive cyclophilin (Cyp) inhibitors such as
      Debio 025, NIM811, and SCY-635 block hepatitis C virus (HCV) replication in
      vitro. This effect was recently confirmed in HCV-infected patients where Debio
      025 treatment dramatically decreased HCV viral load, suggesting that Cyps
      inhibitors represent a novel class of anti-HCV agents. However, it remains
      unclear how these compounds control HCV replication. Recent studies suggest that
      Cyps are important for HCV replication. However, a profound disagreement
      currently exists as to the respective roles of Cyp members in HCV replication. In
      this study, we analyzed the respective contribution of Cyp members to HCV
      replication by specifically knocking down their expression by both transient and
      stable small RNA interference. Only the CypA knockdown drastically decreased HCV
      replication. The re-expression of an exogenous CypA escape protein, which
      contains escape mutations at the small RNA interference recognition site,
      restored HCV replication, demonstrating the specificity for the CypA requirement.
      We then mutated residues that reside in the hydrophobic pocket of CypA where
      proline-containing peptide substrates and cyclosporine A bind and that are vital
      for the enzymatic or the hydrophobic pocket binding activity of CypA. Remarkably,
      these CypA mutants fail to restore HCV replication, suggesting for the first time
      that HCV exploits either the isomerase or the chaperone activity of CypA to
      replicate in hepatocytes and that CypA is the principal mediator of the Cyp
      inhibitor anti-HCV activity. Moreover, we demonstrated that the HCV NS5B
      polymerase associates with CypA via its enzymatic pocket. The study of the roles
      of Cyps in HCV replication should lead to the identification of new targets for
      the development of alternate anti-HCV therapies.

PMID- 19380580
TI  - Severe acute respiratory syndrome coronavirus M protein inhibits type I
      interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon
      complex.
AB  - Severe acute respiratory syndrome (SARS) coronavirus is highly pathogenic in
      humans and evades innate immunity at multiple levels. It has evolved various
      strategies to counteract the production and action of type I interferons, which
      mobilize the front-line defense against viral infection. In this study we
      demonstrate that SARS coronavirus M protein inhibits gene transcription of type I
      interferons. M protein potently antagonizes the activation of interferon
      stimulated response element-dependent transcription by double-stranded RNA, RIG
      I, MDA5, TBK1, IKKepsilon, and virus-induced signaling adaptor (VISA) but has no
      influence on the transcriptional activity of this element when IRF3 or IRF7 is
      overexpressed. M protein physically associates with RIG-I, TBK1, IKKepsilon, and
      TRAF3 and likely sequesters some of them in membrane-associated cytoplasmic
      compartments. Consequently, the expression of M protein prevents the formation of
      TRAF3.TANK.TBK1/IKKepsilon complex and thereby inhibits TBK1/IKKepsilon-dependent
      activation of IRF3/IRF7 transcription factors. Taken together, our findings
      reveal a new mechanism by which SARS coronavirus circumvents the production of
      type I interferons.

PMID- 19380581
TI  - Septin 11 is present in GABAergic synapses and plays a functional role in the
      cytoarchitecture of neurons and GABAergic synaptic connectivity.
AB  - Mass spectrometry and immunoblot analysis of a rat brain fraction enriched in
      type-II postsynaptic densities and postsynaptic GABAergic markers showed
      enrichment in the protein septin 11. Septin 11 is expressed throughout the brain,
      being particularly high in the spiny branchlets of the Purkinje cells in the
      molecular layer of cerebellum and in the olfactory bulb. Immunofluorescence of
      cultured hippocampal neurons showed that 54 +/- 4% of the GABAergic synapses and
      25 +/- 2% of the glutamatergic synapses had colocalizing septin 11 clusters.
      Similar colocalization numbers were found in the molecular layer of cerebellar
      sections. In cultured hippocampal neurons, septin 11 clusters were frequently
      present at the base of dendritic protrusions and at the bifurcation points of the
      dendritic branches. Electron microscopy immunocytochemistry of the rat brain
      cerebellum revealed the accumulation of septin 11 at the neck of dendritic
      spines, at the bifurcation of dendritic branches, and at some GABAergic synapses.
      Knocking down septin 11 in cultured hippocampal neurons with septin 11 small
      hairpin RNAs showed (i) reduced dendritic arborization; (ii) decreased density
      and increased length of dendritic protrusions; and (iii) decreased GABAergic
      synaptic contacts that these neurons receive. The results indicate that septin 11
      plays important roles in the cytoarchitecture of neurons, including dendritic
      arborization and dendritic spines, and that septin 11 also plays a role in
      GABAergic synaptic connectivity.

PMID- 19380582
TI  - Zebrafish eaf1 and eaf2/u19 mediate effective convergence and extension movements
      through the maintenance of wnt11 and wnt5 expression.
AB  - Studies have attributed several functions to the Eaf family, including tumor
      suppression and eye development. Given the potential association between cancer
      and development, we set forth to explore Eaf1 and Eaf2/U19 activity in vertebrate
      embryogenesis, using zebrafish. In situ hybridization revealed similar eaf1 and
      eaf2/u19 expression patterns. Morpholino-mediated knockdown of either eaf1 or
      eaf2/u19 expression produced similar morphological changes that could be reversed
      by ectopic expression of target or reciprocal-target mRNA. However, combination
      of Eaf1 and Eaf2/U19 (Eafs)-morpholinos increased the severity of defects,
      suggesting that Eaf1 and Eaf2/U19 only share some functional redundancy. The Eafs
      knockdown phenotype resembled that of embryos with defects in convergence and
      extension movements. Indeed, knockdown caused expression pattern changes for
      convergence and extension movement markers, whereas cell tracing experiments
      using kaeda mRNA showed a correlation between Eafs knockdown and cell migration
      defects. Cardiac and pancreatic differentiation markers revealed that Eafs
      knockdown also disrupted midline convergence of heart and pancreatic organ
      precursors. Noncanonical Wnt signaling plays a key role in both convergence and
      extension movements and midline convergence of organ precursors. We found that
      Eaf1 and Eaf2/U19 maintained expression levels of wnt11 and wnt5. Moreover, wnt11
      or wnt5 mRNA partially rescued the convergence and extension movement defects
      occurring in eafs morphants. Wnt11 and Wnt5 converge on rhoA, so not
      surprisingly, rhoA mRNA more effectively rescued defects than either wnt11 or
      wnt5 mRNA alone. However, the ectopic expression of wnt11 and wnt5 did not affect
      eaf1 and eaf2/u19 expression. These data indicate that eaf1 and eaf2/u19 act
      upstream of noncanonical Wnt signaling to mediate convergence and extension
      movements.

PMID- 19380583
TI  - Functional characterization of a Na+-dependent aspartate transporter from
      Pyrococcus horikoshii.
AB  - Excitatory amino acid transporters (EAATs) are crucial in maintaining
      extracellular levels of glutamate, the most abundant excitatory neurotransmitter,
      below toxic levels. The recent three-dimensional crystal structure of GltPh, an
      archaeal homolog of the EAATs, provides elegant structural details of this family
      of proteins, yet we know little about the mechanism of the bacterial transporter.
      Conflicting reports in the literature have described GltPh as an aspartate
      transporter driven by Na+ or a glutamate transporter driven by either Na+ or H+.
      Here we use purified protein reconstituted into liposomes to thoroughly
      characterize the ion and substrate dependence of the GltPh transport. We confirm
      that GltPh is a Na+-dependent transporter that is highly selective for aspartate
      over other amino acids, and we show that transport is coupled to at least two Na+
      ions. In contrast to the EAATs, transport via GltPh is independent of H+ and K+.
      We propose a kinetic model of transport in which at least two Na+ ions are
      coupled to the cotransport of each aspartate molecule by GltPh, and where an ion-
      and substrate-free transporter reorients to complete the transport cycle.

PMID- 19380584
TI  - Membrane repair defects in muscular dystrophy are linked to altered interaction
      between MG53, caveolin-3, and dysferlin.
AB  - Defective membrane repair can contribute to the progression of muscular
      dystrophy. Although mutations in caveolin-3 (Cav3) and dysferlin are linked to
      muscular dystrophy in human patients, the molecular mechanism underlying the
      functional interplay between Cav3 and dysferlin in membrane repair of muscle
      physiology and disease has not been fully resolved. We recently discovered that
      mitsugumin 53 (MG53), a muscle-specific TRIM (Tri-partite motif) family protein
      (TRIM72), contributes to intracellular vesicle trafficking and is an essential
      component of the membrane repair machinery in striated muscle. Here we show that
      MG53 interacts with dysferlin and Cav3 to regulate membrane repair in skeletal
      muscle. MG53 mediates active trafficking of intracellular vesicles to the
      sarcolemma and is required for movement of dysferlin to sites of cell injury
      during repair patch formation. Mutations in Cav3 (P104L, R26Q) that cause
      retention of Cav3 in Golgi apparatus result in aberrant localization of MG53 and
      dysferlin in a dominant-negative fashion, leading to defective membrane repair.
      Our data reveal that a molecular complex formed by MG53, dysferlin, and Cav3 is
      essential for repair of muscle membrane damage and also provide a therapeutic
      target for treatment of muscular and cardiovascular diseases that are linked to
      compromised membrane repair.

PMID- 19380585
TI  - Substituted cysteine accessibility method analysis of human concentrative
      nucleoside transporter hCNT3 reveals a novel discontinuous region of functional
      importance within the CNT family motif (G/A)XKX3NEFVA(Y/M/F).
AB  - The human SLC28 family of integral membrane CNT (concentrative nucleoside
      transporter) proteins has three members, hCNT1, hCNT2, and hCNT3. Na(+)-coupled
      hCNT1 and hCNT2 transport pyrimidine and purine nucleosides, respectively,
      whereas hCNT3 mediates transport of both pyrimidine and purine nucleosides
      utilizing Na(+) and/or H(+) electrochemical gradients. These and other eukaryote
      CNTs are currently defined by a putative 13-transmembrane helix (TM) topology
      model with an intracellular N terminus and a glycosylated extracellular C
      terminus. Recent mutagenesis studies, however, have provided evidence supporting
      an alternative 15-TM membrane architecture. In the absence of CNT crystal
      structures, valuable information can be gained about residue localization and
      function using substituted cysteine accessibility method analysis with thiol
      reactive reagents, such as p-chloromercuribenzene sulfonate. Using heterologous
      expression in Xenopus oocytes and the cysteineless hCNT3 protein hCNT3C-,
      substituted cysteine accessibility method analysis with p-chloromercuribenzene
      sulfonate was performed on the TM 11-13 region, including bridging
      extramembranous loops. The results identified residues of functional importance
      and, consistent with a new revised 15-TM CNT membrane architecture, suggest a
      novel membrane-associated topology for a region of the protein (TM 11A) that
      includes the highly conserved CNT family motif (G/A)XKX(3)NEFVA(Y/M/F).

PMID- 19380586
TI  - Role of SUMO in RNF4-mediated promyelocytic leukemia protein (PML) degradation:
      sumoylation of PML and phospho-switch control of its SUMO binding domain
      dissected in living cells.
AB  - Promyelocytic leukemia protein (PML) is a tumor suppressor acting as the
      organizer of subnuclear structures called PML nuclear bodies (NBs). Both covalent
      modification of PML by the small ubiquitin-like modifier (SUMO) and non-covalent
      binding of SUMO to the PML SUMO binding domain (SBD) are necessary for PML NB
      formation and maturation. PML sumoylation and proteasome-dependent degradation
      induced by the E3 ubiquitin ligase, RNF4, are enhanced by the acute promyelocytic
      leukemia therapeutic agent, arsenic trioxide (As2O3). Here, we established a
      novel bioluminescence resonance energy transfer (BRET) assay to dissect and
      monitor PML/SUMO interactions dynamically in living cells upon addition of
      therapeutic agents. Using this sensitive and quantitative SUMO BRET assay that
      distinguishes PML sumoylation from SBD-mediated PML/SUMO non-covalent
      interactions, we probed the respective roles of covalent and non-covalent
      PML/SUMO interactions in PML degradation and interaction with RNF4. We found
      that, although dispensable for As2O3-enhanced PML sumoylation and RNF4
      interaction, PML SBD core sequence was required for As2O3- and RNF4-induced PML
      degradation. As confirmed with a phosphomimetic mutant, phosphorylation of a
      stretch of serine residues, contained within PML SBD was needed for PML
      interaction with SUMO-modified protein partners and thus for NB maturation.
      However, mutation of these serine residues did not impair As2O3- and RNF4-induced
      PML degradation, contrasting with the known role of these phosphoserine residues
      for casein kinase 2-promoted PML degradation. Altogether, these data suggest a
      model whereby sumoylation- and SBD-dependent PML oligomerization within NBs is
      sufficient for RNF4-mediated PML degradation and does not require the
      phosphorylation-dependent association of PML with other sumoylated partners.

PMID- 19380587
TI  - Conserved glutamate residues Glu-343 and Glu-519 provide mechanistic insights
      into cation/nucleoside cotransport by human concentrative nucleoside transporter
      hCNT3.
AB  - Human concentrative nucleoside transporter 3 (hCNT3) utilizes electrochemical
      gradients of both Na(+) and H(+) to accumulate pyrimidine and purine nucleosides
      within cells. We have employed radioisotope flux and electrophysiological
      techniques in combination with site-directed mutagenesis and heterologous
      expression in Xenopus oocytes to identify two conserved pore-lining glutamate
      residues (Glu-343 and Glu-519) with essential roles in hCNT3 Na(+)/nucleoside and
      H(+)/nucleoside cotransport. Mutation of Glu-343 and Glu-519 to aspartate,
      glutamine, and cysteine severely compromised hCNT3 transport function, and
      changes included altered nucleoside and cation activation kinetics (all mutants),
      loss or impairment of H(+) dependence (all mutants), shift in Na(+):nucleoside
      stoichiometry from 2:1 to 1:1 (E519C), complete loss of catalytic activity
      (E519Q) and, similar to the corresponding mutant in Na(+)-specific hCNT1,
      uncoupled Na(+) currents (E343Q). Consistent with close-proximity integration of
      cation/solute-binding sites within a common cation/permeant translocation pore,
      mutation of Glu-343 and Glu-519 also altered hCNT3 nucleoside transport
      selectivity. Both residues were accessible to the external medium and inhibited
      by p-chloromercuribenzene sulfonate when converted to cysteine.

PMID- 19380588
TI  - ZBTB2, a novel master regulator of the p53 pathway.
AB  - We found that ZBTB2, a POK family transcription factor, is a potent repressor of
      the ARF-HDM2-p53-p21 pathway important in cell cycle regulation. ZBTB2 repressed
      transcription of the ARF, p53, and p21 genes, but activated the HDM2 gene. In
      particular, ZBTB2 repressed transcription of the p21 gene by acting on the two
      distal p53 binding elements and the proximal Sp1 binding GC-box 5/6 elements.
      ZBTB2 directly interacted with Sp1 via its POZ domain and zinc fingers, which was
      important in the repression of transcription activation by Sp1. ZBTB2 and Sp1
      competed with each other in binding to the GC-box 5/6 elements and the two p53
      binding elements. ZBTB2 directly interacted with p53 via its zinc fingers,
      inhibiting p53 binding and repressing transcription activation by p53. The POZ
      domain, required for transcription repression, interacted with corepressors such
      as BCoR, NCoR, and SMRT. The interactions deacetylated histones Ac-H3 and -H4 at
      the proximal promoter. Although ectopic ZBTB2 stimulated cell proliferation,
      knock-down of ZBTB2 expression decreased cell proliferation and DNA synthesis.
      Overall, our data suggest that ZBTB2 is a potential proto-oncogenic master
      control gene of the p53 pathway and, in particular, is a potent transcription
      repressor of the cell cycle arrest gene p21 by inhibiting p53 and Sp1.

PMID- 19380589
TI  - Two C-type lectins cooperate to defend Anopheles gambiae against Gram-negative
      bacteria.
AB  - C-type lectins (CTLs) are a family of proteins that share a common structural
      motif, the carbohydrate recognition domain, and may act as receptors in pathogen
      recognition. Indeed, some vertebrate CTLs, particularly the collectins, are
      unequivocally implicated in the innate immune response to certain microbes.
      Although studies in insects and other invertebrates have described CTL activation
      of effector immune responses in vitro, the contribution of these CTLs to immune
      defenses in vivo is still poorly understood. Here we report that two CTLs, CTL4
      and CTLMA2, which were shown previously to inhibit Plasmodium berghei ookinete
      melanization in the malaria vector Anopheles gambiae, are transcriptionally
      induced by bacterial challenge. Using in vivo reverse genetic analysis, we show
      that both CTLs are required for the clearance of Escherichia coli, but not
      Staphylococcus aureus, from adult female mosquitoes. Silencing either CTL
      dramatically reduces mosquito survival to Gram-negative but not to Gram-positive
      bacterial infections, suggesting a role in defense against Gram-negative
      bacteria. Furthermore, molecular characterization reveals that both CTLs are
      secreted into the mosquito hemolymph mainly in the form of a disulfide-linked
      heterodimer. This association explains the similar roles of these CTLs in
      bacterial defense as well as in the melanization response to P. berghei
      ookinetes. Apparently, CTL4 and CTLMA2 serve pleiotropic functions in the innate
      immune response of A. gambiae.

PMID- 19380590
TI  - In vitro activities of echinocandins against Candida krusei determined by three
      methods: MIC and minimal fungicidal concentration measurements and time-kill
      studies.
AB  - We evaluated the in vitro activities of anidulafungin, micafungin, and
      caspofungin against Candida krusei by determining MIC and minimum fungicidal
      concentration (MFC) measurements and by the time-kill method. The geometric mean
      (GM)-MIC/GM-MFC values were 0.1/0.34, 0.25/0.44, and 1/2.29, respectively. The
      mean times to reach 99.9% growth reduction were 19.1 +/- 18.2 h (mean +/-
      standard deviation) for 2 mg/liter anidulafungin, 37.4 +/- 8.8 h for 2 mg/liter
      caspofungin, and 30.7 +/- 12.2 h for 1 mg/liter micafungin. Anidulafungin
      exhibited the highest time-kill rate, followed by micafungin. The three
      echinocandins showed fungicidal activity at concentrations reached in serum.

PMID- 19380591
TI  - Simultaneous determination of voriconazole and posaconazole concentrations in
      human plasma by high-performance liquid chromatography.
AB  - A simple, sensitive, and selective high-performance liquid chromatographic method
      for the simultaneous determination of voriconazole and posaconazole
      concentrations in human plasma was developed and validated. Quantitative recovery
      following liquid-liquid extraction with diethyl ether was achieved. Linearity
      ranged from 0.10 to 20.0 microg/ml for voriconazole and from 0.05 to 10.0
      microg/ml for posaconazole. The intra- and interday coefficients of variation
      were less than 8.5%, and the lower limits of quantitation were <0.05 microg/ml.

PMID- 19380592
TI  - First detection of plasmid-encoded blaOXY beta-lactamase.
AB  - Three Klebsiella oxytoca isolates and one Klebsiella pneumoniae isolate from
      three children admitted to the Hematology Unit of Hospital Vall d'Hebron
      (Barcelona, Spain) exhibited a susceptibility pattern suggesting OXY beta
      lactamase hyperproduction. All the isolates contained a 95-kb plasmid that
      harbored bla(OXY-1), which was transferred by electrotransformation but could not
      be self-transferred by conjugation. A qnrS1 gene was also harbored in the bla(OXY
      1)-carrying plasmid. This is the first report of a plasmid-encoded OXY beta
      lactamase.

PMID- 19380593
TI  - Renal disposition of colistin in the isolated perfused rat kidney.
AB  - Nephrotoxicity is an important limitation to the clinical use of colistin against
      Pseudomonas aeruginosa and other gram-negative pathogens. Previous work reported
      net tubular reabsorption of colistin by the kidney in vivo, but there is no
      knowledge of its disposition within the kidney. This study investigated the renal
      disposition and potential transport mechanisms of colistin in the isolated
      perfused rat kidney (IPK) model by perfusing with colistin sulfate alone (2
      microg/ml) or in the presence of potential inhibitors (tetraethylammonium [TEA],
      glycine-glycine [Gly-Gly], or hydrochloric acid [HCl]) at three different
      concentrations. When perfused alone, the renal clearances (CL(R)) for colistin A
      and B (the major components of colistin) in control kidneys were constant and low
      (mean values < 0.05 ml/min throughout the perfusion). The mean clearance ratios
      [CR, defined as CL(R)/(f(u) x GFR), where f(u) is the fraction of drug unbound in
      perfusate and GFR is the glomerular filtration rate] were significantly less than
      1. It was concluded that there is net tubular reabsorption of colistin, and this
      exceeded the reabsorption of water. Less than 10% eliminated from perfusate was
      recovered in urine, suggesting considerable renal accumulation of colistin. The
      CR values for colistin were significantly increased when perfused with TEA (500
      microM), Gly-Gly (833 microM), and HCl (2,500, 5,000, and 10,000 microM). It is
      proposed that renal reabsorption of colistin may involve organic cation
      transporters (inhibited by TEA) and peptide transporters (inhibited by Gly-Gly)
      and that the process is sensitive to the pH of urine.

PMID- 19380594
TI  - Population modeling and Monte Carlo simulation study of the pharmacokinetics and
      antituberculosis pharmacodynamics of rifampin in lungs.
AB  - Little information exists on the pulmonary pharmacology of antituberculosis
      drugs. We used population pharmacokinetic modeling and Monte Carlo simulation to
      describe and explore the pulmonary pharmacokinetics and pharmacodynamics of
      rifampin (RIF; rifampicin). A population pharmacokinetic model that adequately
      described the plasma, epithelial lining fluid (ELF), and alveolar cell (AC)
      concentrations of RIF in a population of 34 human volunteers was made by use of
      the nonparametric adaptive grid (NPAG) algorithm. The estimated concentrations
      correlated well with the measured concentrations, and there was little bias and
      good precision. The results obtained with the NPAG algorithm were then imported
      into Matlab software to perform a 10,000-subject Monte Carlo simulation. The
      ability of RIF to suppress the development of drug resistance and to induce a
      sufficient bactericidal effect against Mycobacterium tuberculosis was evaluated
      by calculating the proportion of subjects achieving specific target values for
      the maximum concentration of drug (C(max))/MIC ratio and the area under the
      concentration-time curve from time zero to 24 h (AUC(0-24))/MIC ratio,
      respectively. At the lowest MIC (0.01 mg/liter), after the administration of one
      600-mg oral dose, the rates of target attainment for C(max)/MIC (> or =175) were
      95% in ACs, 48.8% in plasma, and 35.9% in ELF. Under the same conditions, the
      target attainment results for the killing effect were 100% in plasma (AUC(0
      24)/MIC > or = 271) but only 54.5% in ELF (AUC(0-24)/MIC > or = 665). The use of
      a 1,200-mg RIF dose was associated with better results for target attainment. The
      overall results suggest that the pulmonary concentrations obtained with the
      standard RIF dose are too low in most subjects. This work supports the need to
      evaluate higher doses of RIF for the treatment of patients with tuberculosis.

PMID- 19380595
TI  - Molecular characteristics of extended-spectrum-beta-lactamase-producing
      Escherichia coli isolates causing bacteremia in the Calgary Health Region from
      2000 to 2007: emergence of clone ST131 as a cause of community-acquired
      infections.
AB  - A study was designed to characterize extended-spectrum-beta-lactamase (ESBL)
      producing Escherichia coli isolates causing bacteremia over an 8-year period
      (2000 to 2007) in a large well-defined geographical region. Molecular
      characterization was done by using isoelectric focusing; PCR; and sequencing of
      the bla(CTX-M)-, bla(TEM)-, bla(OXA)-, bla(SHV)-, and plasmid-mediated quinolone
      resistance determinants. Genetic relatedness was determined by pulsed-field
      electrophoresis with XbaI and multilocus sequence typing. A total of 67 patients
      with incident bloodstream infections were identified, and the majority presented
      with community-acquired infections involving the urinary and biliary tracts. Of
      the 67 ESBL-producing E. coli isolates recovered, 60 (90%) were positive for
      bla(CTX-M) genes; 32 (48%) produced CTX-M-15, 25 (37%) produced CTX-M-14, 1 (2%)
      produced CTX-M-24, 1 (2%) produced CTX-M-2, and 1 (2%) produced CTX-M-3, while 2
      (3%) produced TEM-52 and 5 (7%) produced SHV-2. Twenty-four (36%) isolates were
      positive for aac(6')-Ib-cr. The majority of isolates were resistant to
      ciprofloxacin (60 [90%] isolates) and gentamicin (40 [60%] isolates). The
      occurrence of ESBL-producing isolates was stable during the first 5 years, but
      there was a substantial increase from 2005 to 2007, mostly due to clone ST131,
      which produces CTX-M-15 and CTX-M-14, in blood cultures submitted from the
      community. Our results illustrated that E. coli clone ST131, which coproduces CTX
      M-15, OXA-1, TEM-1, and aac(6')-Ib-cr, has emerged as an important cause of
      community-onset bacteremia caused by ESBL-producing E. coli isolates; and this is
      the first study to identify CTX-M-14 in E. coli clone ST131.

PMID- 19380596
TI  - Genetic and biochemical characterization of the first extended-spectrum CARB-type
      beta-lactamase, RTG-4, from Acinetobacter baumannii.
AB  - Acinetobacter baumannii isolate KAR was uncommonly more resistant to cefepime and
      cefpirome than to ceftazidime and cefotaxime. Cloning and expression of the beta
      lactamase gene content of this isolate into Escherichia coli TOP10 identified ss
      lactamase RTG-4 (or CARB-10), which corresponds to the first reported extended
      spectrum CARB-type enzyme. RTG-4 is a plasmid-encoded Ambler class A beta
      lactamase whose sequence differs by 4 amino acid substitutions from the narrow
      spectrum beta-lactamase RTG-3. RTG-4 hydrolyzes cefepime and cefpirome and weakly
      hydrolyzes ceftazidime due to the single Ser-to-Thr substitution at Ambler
      position 69. RTG-4 is less susceptible to inhibition by tazobactam and sulbactam
      than RTG-3. Expression of beta-lactamase RTG-4 in a wild-type A. baumannii
      reference strain showed that it conferred resistance to cefepime and cefpirome.
      The genetic environment of the bla(RTG-4) gene was made of a peculiar transposon
      located on a ca. 50-kb plasmid. ISAba9, located upstream of bla(RTG-4), may be
      responsible for its acquisition by recognizing a secondary right inverted repeat
      sequence, thus acting by a one-ended transposition process.

PMID- 19380597
TI  - Phase 1/2 double-blind, placebo-controlled, dose escalation, safety, and
      pharmacokinetic study of pagibaximab (BSYX-A110), an antistaphylococcal
      monoclonal antibody for the prevention of staphylococcal bloodstream infections,
      in very-low-birth-weight neonates.
AB  - Staphylococcal sepsis is a major cause of morbidity and mortality in very-low
      birth-weight (VLBW) infants. A human chimeric monoclonal antibody, pagibaximab,
      was developed against staphylococcal lipoteichoic acid. We evaluated the safety,
      tolerability, and pharmacokinetics of pagibaximab in VLBW neonates. A phase 1/2,
      randomized, double-blind, placebo-controlled, dose escalation study was conducted
      in VLBW infants (700 to 1,300 g) 3 to 7 days old. Patients received two doses 14
      days apart of intravenous pagibaximab (10, 30, 60, or 90 mg/kg of body weight) or
      placebo in a 2:1 ratio. Blood and urine samples were obtained pre- and
      postinfusion for analysis of safety and pharmacokinetics, and data on adverse
      events were gathered. Staphylococcal organisms causing sepsis were collected and
      evaluated. Fifty-three patients received at least one dose of pagibaximab or
      placebo. The average gestational age was 27.6 weeks; the average birth weight was
      1,003 g. All serious adverse events were deemed unrelated or probably not drug
      related. Morbidity and mortality were similar across treatment groups. No
      evidence of immunogenicity of pagibaximab was detected. Pagibaximab
      pharmacokinetics was linear. The mean clearance (CL), volume of distribution, and
      elimination half-life of pagibaximab were independent of dose. The serum half
      life was 20.5 +/- 6.8 days. Pagibaximab enhanced serum opsonophagocytic activity.
      All staphylococci causing sepsis were opsonizable by pagibaximab. Two infusions
      of pagibaximab, administered 2 weeks apart to high-risk neonates appeared safe
      and tolerable, and pharmacokinetics were linear. Evaluation of more frequent
      doses, at the highest doses tested, in neonates at high-risk of staphylococcal
      sepsis, is warranted.

PMID- 19380598
TI  - Hypersusceptibility to azole antifungals in a clinical isolate of Candida
      glabrata with reduced aerobic growth.
AB  - Petite mutations have been described in Saccharomyces cerevisiae and pathogenic
      yeasts. However, previous studies of the phenotypic traits of these petite
      mutants reported that they express azole resistance. We describe a clinical
      isolate of Candida glabrata with a striking association between increased
      susceptibility to azoles and respiratory deficiency. This isolate was obtained
      from a urine sample together with a respiration-competent C. glabrata isolate
      which exhibited azole resistance. The respiratory status of the two isolates was
      confirmed by cultivation on glycerol-containing agar and oxygraphy. Flow
      cytometry revealed the normal incorporation of rhodamine 123, and mitochondrial
      sections with typical cristae were seen by transmission electron microscopy for
      both isolates. Together, these results suggested a nuclear origin for the reduced
      respiratory capacity of the hypersusceptible isolate. The sterol contents of
      these isolates were similar to the sterol content of a reference strain.
      Sequencing of the ERG11 and PDR1 genes revealed that the sequences were identical
      in the two isolates, demonstrating their close relatedness. In addition to silent
      mutations, they carried a nonsense mutation in PDR1 that led to the truncation of
      transcription factor Pdr1p. They also overexpressed both PDR1 and one of its
      targets, CDR1, providing a possible explanation for the azole resistance of the
      respiration-competent isolate. In conclusion, in addition to azole resistance,
      which is a common feature of C. glabrata mitochondrial petite mutants, the
      mutation of a nuclear gene affecting aerobic growth may lead to azole
      hypersusceptibility; however, the mechanisms underlying this phenotype remain to
      be determined.

PMID- 19380599
TI  - Sitafloxacin activity against Helicobacter pylori isolates, including those with
      gyrA mutations.
AB  - Sitafloxacin showed MICs of less than or equal to 0.5 microg/ml against 105
      isolates of Helicobacter pylori, including 44 isolates with mutations in the gyrA
      gene. The highest MICs for garenoxacin and levofloxacin were 8 and 64 times,
      respectively, higher than the highest MICs observed for sitafloxacin.

PMID- 19380600
TI  - Piperaquine pharmacodynamics and parasite viability in a murine malaria model.
AB  - Piperaquine (PQ) is an important partner drug in antimalarial combination
      treatments, but the long half-life of PQ raises concerns about drug resistance.
      Our aim was to investigate the extended antimalarial effect of PQ in a study of
      drug efficacy, reinoculation outcomes, and parasite viability after the
      administration of a single dose of PQ in the murine malaria model. Initially,
      male Swiss mice were inoculated with Plasmodium berghei and at 64 h after
      parasite inoculation were given PQ phosphate at 90 mg/kg of body weight
      intraperitoneally. Parasite viability, drug efficacy, reinoculation responses,
      and parasite resistance were determined at 25, 40, 60, 90, and 130 days after
      drug administration. At each time point, six mice were reinoculated with 10(7) P.
      berghei parasites and blood was harvested from another four mice for viability
      passage into naive mice (n = 5 for each blood sample) and from another two mice
      for determination of the plasma PQ concentration. The efficacy study demonstrated
      that the residual PQ concentrations did not suppress the infection after 25 days.
      Viable parasites were present up to 90 days after PQ dosing, although only 50%
      and 25% of the passaged parasites remained viable at 60 and 90 days postdosing,
      respectively. Viable parasites passaged into the naive hosts were generally
      resistant to PQ when they were exposed to the drug for a second time. PQ was
      found to have a substantial antimalarial effect in this model, and the effect
      appears to be sufficient for a host immunological response to be established,
      resulting in the long-term survival of P. berghei-infected mice.

PMID- 19380601
TI  - Comparison of the pharmacodynamics of biapenem in bronchial epithelial lining
      fluid in healthy volunteers given half-hour and three-hour intravenous infusions.
AB  - The time above the MIC (T>MIC) is the pharmacokinetic/pharmacodynamic (PK/PD)
      parameter that correlates with the therapeutic efficacy of beta-lactam
      antibiotics. A prolonged infusion can provide plasma drug concentrations that
      remain above the MIC for a long period. The objective of this study was to
      compare the PK/PD parameters in bronchial epithelial lining fluid (ELF) of
      biapenem given as 0.5-h and 3-h infusions by using bronchoscopic microsampling
      (BMS). Six healthy adult volunteers received 0.5-h and 3-h infusions of 0.3 g of
      biapenem with a washout interval. BMS was performed repeatedly from 0.5 to 24 h
      after biapenem administration in order to determine the pharmacokinetics in
      bronchial ELF. The subjects received intravenous biapenem with the same regimens
      again and then underwent bronchoalveolar lavage (BAL) at the end of infusion in
      order to determine the concentration of the drug in alveolar ELF. The percentages
      (means +/- standard deviations) of T>MIC in bronchial ELF at MICs from 0.25 to 4
      microg/ml ranged from zero to 34.6% +/- 5.2% after the 0.5-h infusion and from
      5.1% +/- 5.6% to 52.2% +/- 17.0% after the 3-h infusion. The percentage of T>MIC
      in bronchial ELF after the 3-h infusion tended to be higher than that after the
      0.5-h infusion. The concentrations of the drug in alveolar ELF after 0.5-h and 3
      h infusions were 3.5 +/- 1.2 microg/ml and 1.3 +/- 0.3 microg/ml, respectively.
      The present results support the use of prolonged infusions of beta-lactam
      antibiotics and may provide critical information for successful treatment of
      lower respiratory tract infections based on PK/PD parameters in bronchial ELF.

PMID- 19380602
TI  - Single-channel analysis of ethanol enhancement of glycine receptor function.
AB  - The glycine receptor (GlyR) is a ligand-gated ion channel and member of the
      nicotinic acetylcholine receptor superfamily. Acting as allosteric modulators of
      receptor function, drugs such as alcohol and volatile anesthetics enhance the
      function of GlyRs. The actions of these drugs at inhibitory receptors in the
      brain and spinal cord are thought to produce many of the physiological effects
      associated with their use. The actions of ethanol on the GlyR have been well
      studied on the macroscopic, whole cell level. We examined the effects of 3 microM
      glycine +/- 50 or 200 mM ethanol on outside-out patches pulled from Xenopus
      laevis oocytes expressing wild-type alpha1 GlyR, to determine the effects of
      alcohol at the single-channel level. Alcohol enhanced GlyR function in a very
      specific manner. It had minimal effects on open and closed dwell times and
      likelihood. Instead, ethanol potentiated GlyR function almost exclusively by
      increasing burst durations and increasing the number of channel openings per
      burst, without affecting the percentage of open time within bursts. Kinetic
      modeling suggests that ethanol increases burst durations by decreasing the rate
      of glycine unbinding.

PMID- 19380603
TI  - Advanced glycation end products subspecies-selectively induce adhesion molecule
      expression and cytokine production in human peripheral blood mononuclear cells.
AB  - Advanced glycation end products (AGEs) are proteins or lipids that become
      glycated after exposure to diverse reducing sugars. Accumulation of AGEs induces
      diabetes complications. Microinflammation is a common major mechanism in the
      pathogenesis of diabetic vascular complications. Activation of
      monocytes/macrophages and T cells plays roles in the pathogenesis of
      atherosclerosis. The activation of T cells requires the enhanced expression of
      adhesion molecules on monocytes. AGEs activate monocytes by engaging the receptor
      for AGE (RAGE); however, little is known about the profile of agonist activity of
      diverse AGE moieties on monocytes. We investigated the effect of four distinct
      AGE subtypes (AGE-modified bovine serum albumin; AGE-2, AGE-3, AGE-4, and AGE-5)
      at concentrations ranging from 0.1 to 100 microg/ml on the expression of
      intercellular adhesion molecule-1, B7.1, B7.2, and CD40 on monocytes and its
      impact on the production of interferon-gamma and tumor necrosis factor-alpha in
      human peripheral blood mononuclear cells. Among the AGEs examined, AGE-2 and AGE
      3 selectively induced adhesion molecule expression and cytokine production.
      Antagonism experiments using antibodies against adhesion molecules demonstrated
      that cell-to-cell interaction between monocytes and T/natural killer cells was
      involved in AGE-2- and AGE-3-induced cytokine production. AGE-2 and AGE-3 up
      regulated the expression of RAGE on monocytes. The effects of AGE-2 and AGE-3
      were inhibited by nuclear factor-kappaB and p38 mitogen-activated protein kinase
      inhibitors. These results indicated that AGE-2 and AGE-3 activated monocytes via
      RAGE, leading to the up-regulation of adhesion molecule expression and cytokine
      production.

PMID- 19380604
TI  - Objective measures of listening effort: effects of background noise and noise
      reduction.
AB  - PURPOSE: This work is aimed at addressing a seeming contradiction related to the
      use of noise-reduction (NR) algorithms in hearing aids. The problem is that
      although some listeners claim a subjective improvement from NR, it has not been
      shown to improve speech intelligibility, often even making it worse. METHOD: To
      address this, the hypothesis tested here is that the positive effects of NR might
      be to reduce cognitive effort directed toward speech reception, making it
      available for other tasks. Normal-hearing individuals participated in 2 dual-task
      experiments, in which 1 task was to report sentences or words in noise set to
      various signal-to-noise ratios. Secondary tasks involved either holding words in
      short-term memory or responding in a complex visual reaction-time task. RESULTS:
      At low values of signal-to-noise ratio, although NR had no positive effect on
      speech reception thresholds, it led to better performance on the word-memory task
      and quicker responses in visual reaction times. CONCLUSIONS: Results from both
      dual tasks support the hypothesis that NR reduces listening effort and frees up
      cognitive resources for other tasks. Future hearing aid research should
      incorporate objective measurements of cognitive benefits.

PMID- 19380606
TI  - Does language influence the accuracy of judgments of stuttering in children?
AB  - PURPOSE: To determine whether stuttering judgment accuracy is influenced by
      familiarity with the stuttering speaker's language. METHOD: Audiovisual 7-min
      speech samples from nine 3- to 5-year-olds were used. Icelandic children who
      stutter (CWS), preselected for different levels of stuttering, were subdivided
      into 5-s intervals. Ten experienced Icelandic speech-language pathologists (ICE
      SLPs) and 10 experienced U.S. speech-language pathologists (US-SLPs), the latter
      being unfamiliar with the Icelandic language, independently judged each 5-s
      interval (n = 756) as stuttered or nonstuttered on 2 separate occasions. RESULTS:
      As in previous studies, intervals judged to contain stuttering showed wide
      variability within the ICE-SLP and US-SLP groups. However, both SLP groups (a)
      displayed satisfactory mean intrajudge agreement, (b) met an independent
      stuttering judgment accuracy criterion test using English-speaking CWS samples,
      and (c) met an agreement criterion on approximately 90% of their stuttering and
      nonstuttering judgments on the Icelandic-speaking CWS samples. CONCLUSION:
      Experienced SLPs were shown to be highly accurate in recognizing stuttering and
      nonstuttering exemplars from young CWS speaking in an unfamiliar language. The
      findings suggest that judgments of occurrences of stuttering in CWS are not
      generally language dependent, although some exceptions were noted.

PMID- 19380605
TI  - Prevalence of hearing loss in Black and White elders: results of the
      Cardiovascular Health Study.
AB  - PURPOSE: The goal of this study was to determine the impact of age, gender, and
      race on the prevalence and severity of hearing loss in elder adults, aged 72-96
      years, after accounting for income, education, smoking, and clinical and
      subclinical cardiovascular disease. Methods Air-conduction thresholds for
      standard and extended high-frequency pure-tones were obtained from a cohort of
      548 (out of 717) elderly adults (ages 72-96 years) who were recruited during the
      Year 11 clinical visit (1999-2000) of the Cardiovascular Health Study (CHS) at
      the Pittsburgh, Pennsylvania site. Participant smoking, income, education, and
      cardiovascular disease histories were obtained from the CHS database and were
      included as factors. RESULTS: Hearing loss was more common and more severe for
      the participants in their 80s than for those in their 70s-the men more than the
      women and the White participants more than the Black participants. The inclusion
      of education, income, smoking, and cardiovascular disease (clinical and
      subclinical) histories as factors did not substantively impact the overall
      results. CONCLUSION: Although the data reported in this article were cross
      sectional and a cohort phenomenon might have been operational, they suggested
      that hearing loss is more substantive in the 8th than the 7th decade of life and
      that race and gender influence this decline in audition. Given the high
      prevalence in the aging population and the differences across groups, there is a
      clear need to understand the nature and causes of hearing loss across various
      groups in order to improve prevention and develop appropriate interventions.

PMID- 19380607
TI  - The lexical restructuring hypothesis and graph theoretic analyses of networks
      based on random lexicons.
AB  - PURPOSE: The mental lexicon of words used for spoken word recognition has been
      modeled as a complex network or graph. Do the characteristics of that graph
      reflect processes involved in its growth (M. S. Vitevitch, 2008) or simply the
      phonetic overlap between similar-sounding words? METHOD: Three pseudolexicons
      were generated by randomly selecting phonological segments from a fixed set. Each
      lexicon was then modeled as a graph, linking words differing by one segment. The
      properties of those graphs were compared with those of a graph based on real
      English words. RESULTS: The properties of the graphs built from the
      pseudolexicons matched the properties of the graph based on English words. Each
      graph consisted of a single large island and a number of smaller islands and
      hermits. The degree distribution of each graph was better fit by an exponential
      than by a power function. Each graph showed short path lengths, large clustering
      coefficients, and positive assortative mixing. CONCLUSION: The results suggest
      that there is no need to appeal to processes of growth or language acquisition to
      explain the formal properties of the network structure of the mental lexicon.
      These properties emerged because the network was built based on the phonetic
      overlap of words.

PMID- 19380608
TI  - Defining spoken language benchmarks and selecting measures of expressive language
      development for young children with autism spectrum disorders.
AB  - PURPOSE: The aims of this article are twofold: (a) to offer a set of recommended
      measures that can be used for evaluating the efficacy of interventions that
      target spoken language acquisition as part of treatment research studies or for
      use in applied settings and (b) to propose and define a common terminology for
      describing levels of spoken language ability in the expressive modality and to
      set benchmarks for determining a child's language level in order to establish a
      framework for comparing outcomes across intervention studies. METHOD: The
      National Institute on Deafness and Other Communication Disorders assembled a
      group of researchers with interests and experience in the study of language
      development and disorders in young children with autism spectrum disorders. The
      group worked for 18 months through a series of conference calls and
      correspondence, culminating in a meeting held in December 2007 to achieve
      consensus on these aims. RESULTS: The authors recommend moving away from using
      the term functional speech, replacing it with a developmental framework. Rather,
      they recommend multiple sources of information to define language phases,
      including natural language samples, parent report, and standardized measures.
      They also provide guidelines and objective criteria for defining children's
      spoken language expression in three major phases that correspond to developmental
      levels between 12 and 48 months of age.

PMID- 19380609
TI  - Perceptual consequences of changes in vocoded speech parameters in various
      reverberation conditions.
AB  - PURPOSE: To study the perceptual consequences of changes in parameters of vocoded
      speech in various reverberation conditions. METHOD: The 3 controlled variables
      were number of vocoder bands, instantaneous frequency change rate, and
      reverberation conditions. The effects were quantified in terms of (a) nonsense
      words' recognition scores for young normal-hearing listeners, (b) ease of
      listening based on the time of response (response delay), and (c) the subjective
      measure of difficulty (10-degree scale). RESULTS: It has been shown that the fine
      structure of a signal is a relevant cue in speech perception in reverberation
      conditions. The results obtained for different number of bands, frequency
      modulation cutoff frequencies, and reverberation conditions have shown that all
      these parameters are important for speech perception in reverberation.
      CONCLUSIONS: Only slow variations in the instantaneous frequency (<50 Hz) seem to
      play a critical role in speech intelligibility in anechoic conditions. In
      reverberant enclosures, however, fast fluctuations of instantaneous frequency are
      also significant.

PMID- 19380610
TI  - Atorvastatin prevents endothelial dysfunction in mesenteric arteries from
      spontaneously hypertensive rats: role of cyclooxygenase 2-derived contracting
      prostanoids.
AB  - We investigated the effect of atorvastatin on cyclooxygenase (COX) contribution
      to endothelial dysfunction in spontaneously hypertensive rat (SHR) mesenteric
      resistance arteries. Atorvastatin (10 mg/kg per day, oral gavage) or its vehicle
      was administered for 2 weeks to male SHR or Wistar-Kyoto rats. Endothelial
      function of mesenteric arteries was assessed by pressurized myograph. In Wistar
      Kyoto rats, relaxation to acetylcholine was inhibited by N(G)-nitro-L-arginine
      methyl ester and unaffected by SC-560 (COX-1 inhibitor), DuP-697 (COX-2
      inhibitor), or ascorbic acid. In SHRs, the response to acetylcholine was
      attenuated, less sensitive to N(G)-nitro-L-arginine methyl ester, unaffected by
      SC-560, and enhanced by DuP-697 or SQ-29548 (thromboxane-prostanoid receptor
      antagonist) to a similar extent. Endothelium-dependent relaxation was normalized
      by ascorbic acid or apocynin (NADPH oxidase inhibitor), which also restored the
      inhibition by N(G)-nitro-L-arginine methyl ester. In atorvastatin-treated SHRs,
      relaxation to acetylcholine was normalized, fully sensitive to N(G)-nitro-L
      arginine methyl ester, and not affected by SC-560, DuP-697, SQ 29548, or
      antioxidants. Dihydroethidium assay showed an increased intravascular superoxide
      generation in SHRs, which was abrogated by atorvastatin. RT-PCR revealed a COX-2
      induction in SHR arteries, which was downregulated by atorvastatin. The release
      of prostacyclin and 8-isoprostane was higher from SHR than Wistar-Kyoto
      mesenteric vessels. COX-2 inhibition and apocynin decreased 8-isoprostane without
      affecting prostacyclin levels. Atorvastatin increased phosphorylated
      extracellular signal-regulated kinase 1/2, pAkt, peNOS(1177), and inducible NO
      synthase levels in SHR mesenteric vessels and decreased 8-isoprostane release. In
      conclusion, COX-2-derived 8-isoprostane contributes to endothelial dysfunction in
      SHR mesenteric arteries. Atorvastatin restores NO availability by increasing
      phosphorylated extracellular signal-regulated kinase 1/2, pAkt, peNOS(1177), and
      inducible NO synthase levels and by abrogating vascular NADPH oxidase-driven
      superoxide production, which also results in a downregulation of COX-2-dependent
      8-isoprostane generation.

PMID- 19380611
TI  - Retrograde flow and shear rate acutely impair endothelial function in humans.
AB  - Changes in arterial shear stress induce functional and structural vasculature
      adaptations. Recent studies indicate that substantial retrograde flow and shear
      can occur through human conduit arteries. In animals, retrograde shear is
      associated with atherogenic effects. The aim of this study was to examine the
      impact of incremental levels of retrograde shear on endothelial function in vivo.
      On 3 separate days, we examined bilateral brachial artery flow-mediated dilation,
      an index of NO-mediated endothelial function, in healthy men (24+/-3 years)
      before and after a 30-minute intervention consisting of cuff inflation to 25, 50,
      or 75 mm Hg. Cuff inflations resulted in "dose"-dependent increases in retrograde
      shear rate, compared with the noncuffed arm, within subjects (P<0.001). Flow
      mediated dilation in the cuffed arm did not change in response to the 25-mm Hg
      stimulus but decreased significantly after both the 50- and 75-mm Hg
      interventions (P<0.05). The decrease in flow-mediated dilation after the 75-mm Hg
      intervention was significantly larger than that observed after a 50-mm Hg
      intervention (P=0.03). In the noncuffed arm, no changes in shear rate or flow
      mediated dilation were observed. These results demonstrate that an increase in
      retrograde shear rate induces a dose-dependent attenuation of endothelial
      function in humans. This finding contributes to our understanding regarding the
      possible detrimental effects of retrograde shear rate in vivo.

PMID- 19380612
TI  - Programming of hypertension: associations of plasma aldosterone in adult men and
      women with birthweight, cortisol, and blood pressure.
AB  - Animal models suggest that explanations for the association of low birthweight
      with adult hypertension may include chronic activation of the hypothalamic
      pituitary-adrenal or renin-angiotensin-aldosterone axes. In humans, low
      birthweight predicts elevated plasma cortisol, but associations with aldosterone
      have not been reported. We measured aldosterone in serum samples from 205 men and
      106 women from 67 to 78 years of age, from Hertfordshire, UK, for whom
      birthweight was recorded. Participants underwent an overnight low-dose (0.25 mg)
      dexamethasone suppression test and a low-dose (1 mug) ACTH (corticotropin)
      stimulation test and were genotyped for the -344 C/T polymorphism of the CYP11B2
      gene encoding aldosterone synthase. Median aldosterone was 6.22 ng/dL (range 0.15
      to 38.74) and was higher in men than women (P<0.0001). Higher aldosterone levels
      after both dexamethasone and ACTH stimulation were associated with higher blood
      pressure (r=0.20, P=0.001; r=0.33, P<0.0001, respectively) and with lower
      birthweight (r=-0.16, P=0.008; r=-0.21, P=0.001, respectively). These
      associations remained significant after adjusting for age, gender, obesity, and
      genotype. Our findings supplement previous evidence that aldosterone is an
      important regulator of blood pressure and suggest that factors in early life that
      retard fetal growth and program activation of the hypothalamic-pituitary-adrenal
      axis in humans result not only in higher glucocorticoid activity but also in
      increased mineralocorticoid activity.

PMID- 19380613
TI  - Soluble form of the (pro)renin receptor generated by intracellular cleavage by
      furin is secreted in plasma.
AB  - The (pro)renin receptor [(P)RR] is a 35-kDa transmembrane protein that plays a
      pivotal role in angiotensin tissue generation and in nonproteolytic prorenin
      activation. We detected a soluble form of (P)RR [s(P)RR; 28 kDa] in the
      conditioned medium of cultured cells. The aims of our study were to identify the
      protease responsible for the generation of s(P)RR, the site of shedding, and to
      establish the existence of circulating s(P)RR in plasma. We identified furin as
      the protease responsible for the shedding of endogenous (P)RR based on the
      following: LoVo colon carcinoma cells devoid of active furin synthesize full
      length (P)RR but do not secrete s(P)RR; transfection of Chinese hamster ovary
      cells with a plasmid coding for alpha1-antitrypsin Portland variant, an inhibitor
      of furin, completely inhibited the generation of s(P)RR, whereas addition of
      GM6001, an inhibitor of metalloproteases or of tumor necrosis factor-alpha
      protease inhibitor-1, an inhibitor of ADAM17, in the culture medium has no
      effect; when the cDNA coding for (P)RR was translated in vitro and incubated with
      recombinant furin or ADAM17, only furin was able to generate the 28 kDa-s(P)RR,
      and mutagenesis in the potential furin cleavage R275A/KT/R278A site abolished
      s(P)RR generation. Immunofluorescence study in glomerular epithelial cells showed
      that (P)RR was cleaved in the trans-Golgi, and coprecipitation experiments with
      renin showed that s(P)RR was present in plasma. In conclusion, our results show
      that s(P)RR is generated intracellularly by furin cleavage, and that s(P)RR
      detected in plasma is able to bind renin.

PMID- 19380614
TI  - Does wave reflection dominate age-related change in aortic blood pressure across
      the human life span?
AB  - Aortic systolic and pulse pressure rise with age because of aortic stiffening.
      Two factors are responsible: a larger incident wave because of increased aortic
      characteristic impedance and premature return of wave reflection from peripheral
      sites. This study aimed to determine the relative contribution of each factor
      before and after age 60 years. Aortic pressure waveforms were generated for 3682
      healthy subjects using a generalized transfer function applied to radial pressure
      waveforms recorded by applanation tonometry. Linear regression and product of
      coefficient mediation analysis were performed in the cross-sectional cohort to
      determine the yearly contribution of the incident and reflected waves (waves
      measured as first systolic peak and augmented pressure, respectively) to aortic
      systolic and pulse pressure elevation with age. This was done separately for
      subjects <or=60 and >60 years of age, with both sexes initially pooled and
      subsequently separated. Analyses were repeated with correction for height,
      weight, heart rate, and mean arterial pressure. Before age 60 years, the
      reflected wave was a greater (P<0.05) contributor to age-related aortic systolic
      and pulse pressure elevations, with no significant contribution of the incident
      wave in this age group in sex-pooled analysis. After age 60 years, both incident
      and reflected waves were significant (P<0.05) and comparable contributors (P
      difference >0.05) to age-related aortic systolic and pulse pressure elevations.
      This general pattern was observed in both sexes and persisted after correction
      for confounders. Wave reflection is important across the life span, whereas
      aortic characteristic impedance contributes significantly only beyond age 60
      years.

PMID- 19380615
TI  - Prenatal cocaine exposure differentially causes vascular dysfunction in adult
      offspring.
AB  - Epidemiological studies have shown a clear association of adverse intrauterine
      environment and an increased risk of cardiovascular diseases and hypertension in
      adult life. The present study tested the hypothesis that prenatal cocaine
      exposure causes reprogramming of vascular reactivity, leading to an increased
      risk of hypertension in adult offspring. Pregnant rats received cocaine (30 mg
      kg(-1) day(-1)) or saline from days 15 to 21 of gestational age, and experiments
      were conducted in 3-month-old offspring. Cocaine had no effect on the baseline
      blood pressure but significantly increased norepinephrine-stimulated blood
      pressure and decreased the baroreflex sensitivity in male but not female
      offspring. The cocaine treatment significantly increased norepinephrine-induced
      contractions in pressurized resistance-sized mesenteric arteries but not in
      aortas, which was primarily because of a loss of endothelial NO synthase-mediated
      inhibition and an enhanced Ca(2+) sensitivity in mesenteric arteries. In
      addition, the cocaine treatment significantly attenuated the endothelium
      dependent relaxation in mesenteric arteries in male but not female offspring.
      Endothelial NO synthase protein levels in aortas but not mesenteric arteries were
      significantly increased in the cocaine-treated animals. However, cocaine
      significantly decreased phosphorylation levels of endothelial NO synthase in both
      aortas and mesenteric arteries. The results suggest that prenatal cocaine
      exposure programs vascular contractility via changes in endothelial NO synthase
      regulated Ca(2+) sensitivity of myofilaments in the sex- and tissue-dependent
      manners in resistance arteries leading to an increased risk of hypertension in
      male offspring.

PMID- 19380616
TI  - D1-like receptors regulate NADPH oxidase activity and subunit expression in lipid
      raft microdomains of renal proximal tubule cells.
AB  - NADPH oxidase (Nox)-dependent reactive oxygen species production is implicated in
      the pathogenesis of cardiovascular diseases, including hypertension. We tested
      the hypothesis that oxidase subunits are differentially regulated in renal
      proximal tubules from normotensive and spontaneously hypertensive rats. Basal
      Nox2 and Nox4, but not Rac1, in immortalized renal proximal tubule cells and
      brush border membranes were greater in hypertensive than in normotensive rats.
      However, more Rac1 was expressed in lipid rafts in cells from hypertensive rats
      than in cells from normotensive rats; the converse was observed with Nox4,
      whereas Nox2 expression was similar. The D(1)-like receptor agonist fenoldopam
      decreased Nox2 and Rac1 protein in lipid rafts to a greater extent in
      hypertensive than in normotensive rats. Basal oxidase activity was 3-fold higher
      in hypertensive than in normotensive rats but was inhibited to a greater extent
      by fenoldopam in normotensive (58+/-3.3%) than in hypertensive rats (31+/-5.2%;
      P<0.05; n=6 per group). Fenoldopam decreased the amount of Nox2 that
      coimmunoprecipitated with p67(phox) in cells from normotensive rats. D(1)-like
      receptors may decrease oxidase activity by disrupting the distribution and
      assembly of oxidase subunits in cell membrane microdomains. The cholesterol
      depleting reagent methyl-beta-cyclodextrin decreased oxidase activity and
      cholesterol content to a greater extent in hypertensive than in normotensive
      rats. The greater basal levels of Nox2 and Nox4 in cell membranes and Nox2 and
      Rac1 in lipid rafts in hypertensive rats than in normotensive rats may explain
      the increased basal oxidase activity in hypertensive rats.

PMID- 19380617
TI  - Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived
      hyperpolarizing factor vasodilator pathway and causes hypertension.
AB  - BACKGROUND: It has been proposed that activation of endothelial SK3 (K(Ca)2.3)
      and IK1 (K(Ca)3.1) K+ channels plays a role in the arteriolar dilation attributed
      to an endothelium-derived hyperpolarizing factor (EDHF). However, our
      understanding of the precise function of SK3 and IK1 in the EDHF dilator response
      and in blood pressure control remains incomplete. To clarify the roles of SK3 and
      IK1 channels in the EDHF dilator response and their contribution to blood
      pressure control in vivo, we generated mice deficient for both channels. METHODS
      AND RESULTS: Expression and function of endothelial SK3 and IK1 in IK1(-/
      )/SK3(T/T) mice was characterized by patch-clamp, membrane potential
      measurements, pressure myography, and intravital microscopy. Blood pressure was
      measured in conscious mice by telemetry. Combined IK1/SK3 deficiency in IK1(-/
      )/SK3(T/T) (+doxycycline) mice abolished endothelial K(Ca) currents and impaired
      acetylcholine-induced smooth muscle hyperpolarization and EDHF-mediated dilation
      in conduit arteries and in resistance arterioles in vivo. IK1 deficiency had a
      severe impact on acetylcholine-induced EDHF-mediated vasodilation, whereas SK3
      deficiency impaired NO-mediated dilation to acetylcholine and to shear stress
      stimulation. As a consequence, SK3/IK1-deficient mice exhibited an elevated
      arterial blood pressure, which was most prominent during physical activity.
      Overexpression of SK3 in IK1(-/-)/SK3(T/T) mice partially restored EDHF- and
      nitric oxide-mediated vasodilation and lowered elevated blood pressure. The IK1
      opener SKA-31 enhanced EDHF-mediated vasodilation and lowered blood pressure in
      SK3-deficient IK1(+/+)/SK3(T/T) (+doxycycline) mice to normotensive levels.
      CONCLUSIONS: Our study demonstrates that endothelial SK3 and IK1 channels have
      distinct stimulus-dependent functions, are major players in the EDHF pathway, and
      significantly contribute to arterial blood pressure regulation. Endothelial K(Ca)
      channels may represent novel therapeutic targets for the treatment of
      hypertension.

PMID- 19380618
TI  - Macrophage-specific expression of mannose-binding lectin controls atherosclerosis
      in low-density lipoprotein receptor-deficient mice.
AB  - BACKGROUND: With consideration of the central role of the innate immune system in
      atherogenesis and mannose-binding lectin (MBL) as an innate regulator of
      immunity, the role of MBL in experimental and human atherosclerosis was assessed.
      METHODS AND RESULTS: With the use of immunohistochemistry and polymerase chain
      reaction, deposition and gene expression of MBL-A and -C were assessed in murine
      atherosclerosis from mice deficient for the low-density lipoprotein receptor
      (LDLR(-/-)) after 10 or 18 weeks of high-fat feeding. MBL was present and was
      produced in 10-week-old lesions, whereas deposition and gene expression were
      minimal after 18 weeks of high-fat feeding and absent in healthy vasculature.
      Interestingly, deposition of MBL-A and -C differed: MBL-A predominantly localized
      in upper medial layers, whereas MBL-C was found in and around intimal
      macrophages. To further study the role of local MBL production by monocytic cells
      in atherosclerosis, LDLR(-/-) mice with MBL-A and -C(-/-) monocytic cells were
      construed by bone marrow transplantation. Mice carrying MBL-A and -C double
      deficient macrophages had increased (30%) atherosclerotic lesions compared with
      wild-type controls (P=0.015) after 10 weeks of high-fat diet. Subsequently,
      analysis of MBL deposition and gene expression in advanced human atherosclerotic
      lesions revealed the presence of MBL protein in ruptured but not stable
      atherosclerotic lesions. Putatively in agreement with murine data, no MBL gene
      expression could be detected in advanced human atherosclerotic lesions.
      CONCLUSIONS: These results are the first to show that MBL is abundantly present
      and locally produced during early atherogenesis. Local MBL expression, by myeloid
      cells, is shown to critically control development of atherosclerotic lesions.

PMID- 19380619
TI  - Peripheral arterial disease is associated with higher rates of hip bone loss and
      increased fracture risk in older men.
AB  - BACKGROUND: Peripheral arterial disease (PAD) and osteoporosis are chronic
      illnesses that increase in prevalence with aging and certain metabolic disorders.
      The association between PAD, rates of bone loss, and fracture risk in older men
      is uncertain. METHODS AND RESULTS: We sought to test the hypothesis that PAD is
      associated with higher rates of bone loss and increased fracture risk. We
      analyzed data from a prospective cohort study involving 6 US centers and 5781 men
      at least 65 years of age. We assessed ankle-brachial index and hip bone mineral
      density, followed up prospectively for changes in hip bone mineral density and
      fractures. PAD was defined as a baseline ankle-brachial index <0.9. Hip bone
      mineral density was measured with dual x-ray absorptiometry at baseline and again
      an average of 4.6 years later. Incident nonspine fractures were ascertained by
      self-report and confirmed with radiography reports during an average of 5.4 years
      of follow-up. At baseline, the prevalence of PAD was 6.2%. After adjustment for
      age, race, site, and baseline bone mineral density, the mean annualized rate of
      bone loss at the total hip was -0.66% per year (95% confidence interval -0.78 to 
      0.54) in men with PAD compared with -0.34% per year (95% confidence interval 
      0.36 to -0.31) in men without PAD (P<0.001). After further adjustment for
      multiple potential confounders, the difference was attenuated (-0.49% in men with
      PAD versus -0.35% in men without PAD) but remained significant (P=0.02). Findings
      were similar at hip subregions. Twelve percent of men with PAD and 7.9% of those
      without PAD experienced an incident nonspine fracture (hazard ratio adjusted for
      age, race, and site=1.47, 95% confidence interval 1.07 to 2.04); this association
      was not altered substantially by further adjustment for multiple confounders.
      CONCLUSIONS: In community-dwelling older men, PAD was associated with higher
      rates of hip bone loss and increased risk of nonspine fractures. Further research
      should examine the biological mechanisms underlying the association between
      reduced limb blood flow and fractures.

PMID- 19380620
TI  - MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury
      by targeting heat-shock protein 20.
AB  - BACKGROUND: Recent studies have identified critical roles for microRNAs (miRNAs)
      in a variety of cellular processes, including regulation of cardiomyocyte death.
      However, the signature of miRNA expression and possible roles of miRNA in the
      ischemic heart have been less well studied. METHODS AND RESULTS: We performed
      miRNA arrays to detect the expression pattern of miRNAs in murine hearts
      subjected to ischemia/reperfusion (I/R) in vivo and ex vivo. Surprisingly, we
      found that only miR-320 expression was significantly decreased in the hearts on
      I/R in vivo and ex vivo. This was further confirmed by TaqMan real-time
      polymerase chain reaction. Gain-of-function and loss-of-function approaches were
      employed in cultured adult rat cardiomyocytes to investigate the functional roles
      of miR-320. Overexpression of miR-320 enhanced cardiomyocyte death and apoptosis,
      whereas knockdown was cytoprotective, on simulated I/R. Furthermore, transgenic
      mice with cardiac-specific overexpression of miR-320 revealed an increased extent
      of apoptosis and infarction size in the hearts on I/R in vivo and ex vivo
      relative to the wild-type controls. Conversely, in vivo treatment with antagomir
      320 reduced infarction size relative to the administration of mutant antagomir
      320 and saline controls. Using TargetScan software and proteomic analysis, we
      identified heat-shock protein 20 (Hsp20), a known cardioprotective protein, as an
      important candidate target for miR-320. This was validated experimentally by
      utilizing a luciferase/GFP reporter activity assay and examining the expression
      of Hsp20 on miR-320 overexpression and knockdown in cardiomyocytes. CONCLUSIONS:
      Our data demonstrate that miR-320 is involved in the regulation of I/R-induced
      cardiac injury and dysfunction via antithetical regulation of Hsp20. Thus, miR
      320 may constitute a new therapeutic target for ischemic heart diseases.

PMID- 19380622
TI  - Conventional dendritic cells at the crossroads between immunity and cholesterol
      homeostasis in atherosclerosis.
AB  - BACKGROUND: Immunoinflammatory mechanisms are implicated in the atherogenic
      process. The polarization of the immune response and the nature of the immune
      cells involved, however, are major determinants of the net effect, which may be
      either proatherogenic or antiatherogenic. Dendritic cells (DCs) are central to
      the regulation of immunity, the polarization of the immune response, and the
      induction of tolerance to antigens. The potential role of DCs in atherosclerosis,
      however, remains to be defined. METHODS AND RESULTS: We created a mouse model in
      which the lifespan and immunogenicity of conventional DCs are enhanced by
      specific overexpression of the antiapoptotic gene hBcl-2 under the control of the
      CD11c promoter. When studied in either low-density lipoprotein receptor-deficient
      or apolipoprotein E-deficient backgrounds, DC-hBcl2 mice exhibited an expanded DC
      population associated with enhanced T-cell activation, a T-helper 1 and T-helper
      17 cytokine expression profile, and elevated production of T-helper 1-driven
      IgG2c autoantibodies directed against oxidation-specific epitopes. This
      proatherogenic signature, however, was not associated with acceleration of
      atherosclerotic plaque progression, because expansion of the DC population was
      unexpectedly associated with an atheroprotective decrease in plasma cholesterol
      levels. Conversely, depletion of DCs in hyperlipidemic CD11c-diphtheria toxin
      receptor/apolipoprotein E-deficient transgenic mice resulted in enhanced
      cholesterolemia, thereby arguing for a close relationship between the DC
      population and plasma cholesterol levels. CONCLUSIONS: Considered together, the
      present data reveal that conventional DCs are central to the atherosclerotic
      process, because they are directly implicated in both cholesterol homeostasis and
      the immune response.

PMID- 19380621
TI  - Aortic arch plaques and risk of recurrent stroke and death.
AB  - BACKGROUND: Aortic arch plaques are a risk factor for ischemic stroke. Although
      the stroke mechanism is conceivably thromboembolic, no randomized studies have
      evaluated the efficacy of antithrombotic therapies in preventing recurrent
      events. METHODS AND RESULTS: The relationship between arch plaques and recurrent
      events was studied in 516 patients with ischemic stroke who were double-blindly
      randomized to treatment with warfarin or aspirin as part of the Patent Foramen
      Ovale in Cryptogenic Stroke Study (PICSS), based on the Warfarin-Aspirin
      Recurrent Stroke Study (WARSS). Plaque thickness and morphology were evaluated by
      transesophageal echocardiography. End points were recurrent ischemic stroke or
      death over a 2-year follow-up. Large plaques (> or =4 mm) were present in 19.6%
      of patients; large complex plaques (those with ulcerations or mobile components)
      were seen in 8.5%. During follow-up, large plaques were associated with a
      significantly increased risk of events (adjusted hazard ratio [HR], 2.12; 95%
      confidence interval [CI], 1.04 to 4.32), especially those with complex morphology
      (HR, 2.55; 95 CI, 1.10 to 5.89). The risk was highest among cryptogenic stroke
      patients, both for large plaques (HR, 6.42; 95% CI, 1.62 to 25.46) and large
      complex plaques (HR, 9.50; 95% CI, 1.92 to 47.10). Event rates were similar in
      the warfarin and aspirin groups in the overall study population (16.4% versus
      15.8%; P=0.43). CONCLUSIONS: In patients with stroke, especially cryptogenic
      stroke, large aortic plaques remain associated with an increased risk of
      recurrent stroke and death at 2 years despite treatment with warfarin or aspirin.
      Complex plaque morphology confers a slight additional increase in risk.

PMID- 19380623
TI  - One-year clinical outcomes, midterm survival, and predictors of mortality after
      carotid stenting in elderly patients.
AB  - BACKGROUND: It has been demonstrated recently that carotid stenting can be
      performed safely in patients > or =80 years of age. However, it is uncertain
      whether these patients will derive benefit because longevity after
      revascularization is an important consideration. This study was conducted to
      determine survival and predictors of mortality of selected elderly patients after
      stenting. METHODS AND RESULTS: One hundred forty-two consecutive elderly patients
      who were non-high risk for stenting underwent 153 procedures. Patients had either
      symptomatic stenosis > or =50% or asymptomatic stenosis > or =70%. Demographics
      and in-hospital outcomes were entered into a database; subsequent outcomes and
      mortality data were obtained retrospectively. Mean+/-SD age was 83.3+/-3.1 years.
      Symptomatic patients accounted for 28%. Overall survival at 3 years was 76% (85%
      at 2 years). At 1 year, 1 fatal stroke had occurred, with 97% of survivors
      (n=114) free of neurological events (neurological status was undetermined in the
      remaining 3%). Predictors of mortality were remote (> or =6 months) transient
      ischemic attack or cerebrovascular accident, smoking history, and creatinine
      clearance (hemoglobin level showed a strong trend toward achieving significance);
      for the asymptomatic subgroup, predictors of mortality were smoking history,
      previous carotid endarterectomy, hemoglobin level, and increasing age. In
      particular, symptom status and sex were not independent predictors of mortality.
      CONCLUSIONS: This study demonstrates that in selected elderly patients, a high
      proportion (85%) survived 2 years and >75% survived 3 years after stenting.
      Carotid stenting may be considered a revascularization option in such patients.
      Better selection of patients using the predictors of mortality may help to reduce
      unwarranted procedures and to optimize survival likelihood.

PMID- 19380624
TI  - Unprotected left main stenting in the real world: two-year outcomes of the French
      left main taxus registry.
AB  - BACKGROUND: Cardiac surgery is the reference treatment for patients with left
      main (LM) disease, although percutaneous coronary intervention with drug-eluting
      stents is emerging as a possible alternative. The objective of this registry was
      to evaluate the 2-year outcome of elective percutaneous coronary intervention for
      unprotected LM disease with paclitaxel-eluting stents. METHODS AND RESULTS: A
      total of 291 patients were prospectively included from 4 centers. Acute
      myocardial infarction and cardiogenic shock were the only exclusion criteria.
      Patients were 69+/-11 years old, 29% were diabetic, and 25% had 3-vessel disease.
      For distal LM lesions (78%), the provisional side-branch T-stenting approach was
      used in 92% of cases and final kissing balloon inflation in 97%. Angiographic
      success was obtained in 99.7% of cases. At 2-year follow-up, the total cardiac
      death rate was 5.4% (1 EuroSCORE point was associated with a 15% [95% confidence
      interval 2.9% to 28.2%, P=0.013] higher risk of cardiac death), target-lesion
      revascularization was 8.7%, and incidence of Q-wave or non-Q-wave myocardial
      infarction was 0.9% and 3.1%, respectively. The combined end point occurred in
      15.8% of cases and stroke in 0.7%. The incidence of definite and probable LM
      stent thrombosis was 0.7%, whereas the incidence of any stent thrombosis was
      3.8%, with a higher risk in patients with side-branch stenting in the presence of
      LM bifurcation lesions (hazard ratio 9.6, 95% confidence interval 1.2 to 77.7,
      P=0.035). CONCLUSIONS: Unprotected LM stenting with paclitaxel-eluting stents,
      with a strategy of provisional side-branch T-stenting for distal lesions,
      provides excellent acute angiographic results and good mid-term clinical
      outcomes, with a 15.8% rate of major adverse cardiac events at 2-year follow-up.

PMID- 19380625
TI  - Evaluation of the novel myocardial perfusion positron-emission tomography tracer
      18F-BMS-747158-02: comparison to 13N-ammonia and validation with microspheres in
      a pig model.
AB  - BACKGROUND: Positron-emission tomography (PET) tracers for myocardial perfusion
      are commonly labeled with short-lived isotopes that limit their widespread
      clinical use. 18F-BMS-747158-02 (18F-BMS) is a novel pyridaben derivative that
      was evaluated for assessment of myocardial perfusion by comparison with 13N
      ammonia (13NH3) and with radioactive microspheres in a pig model. METHODS AND
      RESULTS: Fourteen pigs injected with 500 MBq of 13NH3 or 100 to 200 MBq of 18F
      BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of
      these pigs, 18F-BMS was injected during stress combined with transient, 2.5
      minute constriction of the left anterior descending coronary artery. Radioactive
      microspheres were coinjected with 18F-BMS. Ratios of myocardial tracer uptake to
      surrounding tissues were determined, and myocardial blood flow was quantified by
      compartmental modeling. Both tracers showed high and homogeneous myocardial
      uptake. Compared with 13NH3, 18F-BMS showed higher activity ratios between
      myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest
      1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress
      2.9 versus 6.4). Regional myocardial blood flow assessed with 18F-BMS PET showed
      good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th
      percentile -0.3, 75th percentile 0.1 mL x min(-1) x g(-1)]) with that measured
      with radioactive microspheres over a flow range from 0.1 to 3.0 mL x min(-1) x g(
      1). The extent of defects induced by left anterior descending coronary artery
      constriction measured by 18F-BMS and microspheres also correlated closely
      (r=0.63, slope=1.1). CONCLUSIONS: 18F-BMS-747158-02 is a very attractive new PET
      perfusion tracer that allows quantitative assessment of regional myocardial
      perfusion over a wide flow range. The long half-life of 18F renders this tracer
      useful for clinical PET/CT applications in the workup of patients with suspected
      or proven coronary artery disease.

PMID- 19380627
TI  - Cardiology patient pages. The Surgeon General's call to action to prevent deep
      vein thrombosis and pulmonary embolism.

PMID- 19380626
TI  - A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated
      with idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: Excessive proliferation of pulmonary artery smooth muscle cells
      (PASMCs) plays an important role in the development of idiopathic pulmonary
      arterial hypertension (IPAH), whereas a rise in cytosolic Ca2+ concentration
      triggers PASMC contraction and stimulates PASMC proliferation. Recently, we
      demonstrated that upregulation of the TRPC6 channel contributes to proliferation
      of PASMCs isolated from IPAH patients. This study sought to identify single
      nucleotide polymorphisms (SNPs) in the TRPC6 gene promoter that are associated
      with IPAH and have functional significance in regulating TRPC6 activity in
      PASMCs. METHODS AND RESULTS: Genomic DNA was isolated from blood samples of 237
      normal subjects and 268 IPAH patients. Three biallelic SNPs, -361 (A/T), 
      254(C/G), and -218 (C/T), were identified in the 2000-bp sequence upstream of the
      transcriptional start site of TRPC6. Although the allele frequencies of the -361
      and -218 SNPs were not different between the groups, the allele frequency of the 
      254(C-->G) SNP in IPAH patients (12%) was significantly higher than in normal
      subjects (6%; P<0.01). Genotype data showed that the percentage of -254G/G
      homozygotes in IPAH patients was 2.85 times that of normal subjects. Moreover,
      the -254(C-->G) SNP creates a binding sequence for nuclear factor-kappaB.
      Functional analyses revealed that the -254(C-->G) SNP enhanced nuclear factor
      kappaB-mediated promoter activity and stimulated TRPC6 expression in PASMCs.
      Inhibition of nuclear factor-kappaB activity attenuated TRPC6 expression and
      decreased agonist-activated Ca2+ influx in PASMCs of IPAH patients harboring the 
      254G allele. CONCLUSIONS: These results suggest that the -254(C-->G) SNP may
      predispose individuals to an increased risk of IPAH by linking abnormal TRPC6
      transcription to nuclear factor-kappaB, an inflammatory transcription factor.

PMID- 19380628
TI  - Images in cardiovascular medicine: Pentalogy of Cantrell associated with
      thoracoabdominal ectopia cordis.

PMID- 19380629
TI  - Letter by Singh regarding article, "Does sodium nitroprusside decrease the
      incidence of atrial fibrillation after myocardial revascularization? A pilot
      study".

PMID- 19380631
TI  - Lost in translation: modulation of the metabolic-functional relation in the
      diabetic human heart.

PMID- 19380632
TI  - Science of emergency medical dispatch.

PMID- 19380633
TI  - Images in cardiovascular medicine: Delayed right ventricular perforation by a
      transvenous active fixation implantable cardioverter-defibrillator lead:
      echocardiographic diagnosis and surgical management.

PMID- 19380635
TI  - The activation-induced cytidine deaminase (AID) efficiently targets DNA in
      nucleosomes but only during transcription.
AB  - The activation-induced cytidine deaminase (AID) initiates somatic hypermutation,
      class-switch recombination, and gene conversion of immunoglobulin genes. In
      vitro, AID has been shown to target single-stranded DNA, relaxed double-stranded
      DNA, when transcribed, or supercoiled DNA. To simulate the in vivo situation more
      closely, we have introduced two copies of a nucleosome positioning sequence, MP2,
      into a supercoiled AID target plasmid to determine where around the positioned
      nucleosomes (in the vicinity of an ampicillin resistance gene) cytidine
      deaminations occur in the absence or presence of transcription. We found that
      without transcription nucleosomes prevented cytidine deamination by AID. However,
      with transcription AID readily accessed DNA in nucleosomes on both DNA strands.
      The experiments also showed that AID targeting any DNA molecule was the limiting
      step, and they support the conclusion that once targeted to DNA, AID acts
      processively in naked DNA and DNA organized within transcribed nucleosomes.

PMID- 19380636
TI  - A20 takes on tumors: tumor suppression by an ubiquitin-editing enzyme.
AB  - Many B cell cancers are characterized in part by the dysregulation of the NF
      kappaB signaling pathway. A new study identifies somatic mutations in TNFAIP3,
      the gene encoding the NF-kappaB inhibitor A20, in Hodgkin lymphomas and primary
      mediastinal lymphomas. These data reveal the role of A20 as a tumor suppressor
      protein.

PMID- 19380637
TI  - T follicular helper cells differentiate from Th2 cells in response to helminth
      antigens.
AB  - The relationship of T follicular helper (TFH) cells to other T helper (Th)
      subsets is controversial. We find that after helminth infection, or immunization
      with helminth antigens, reactive lymphoid organs of 4get IL-4/GFP reporter mice
      contain populations of IL-4/GFP-expressing CD4(+) T cells that display the TFH
      markers CXCR5, PD-1, and ICOS. These TFH cells express the canonical TFH markers
      BCL6 and IL-21, but also GATA3, the master regulator of Th2 cell differentiation.
      Consistent with a relationship between Th2 and TFH cells, IL-4 protein
      production, reported by expression of huCD2 in IL-4 dual reporter (4get/KN2)
      mice, was a robust marker of TFH cells in LNs responding to helminth antigens.
      Moreover, the majority of huCD2/IL-4-producing Th cells were found within B cell
      follicles, consistent with their definition as TFH cells. TFH cell development
      after immunization failed to occur in mice lacking B cells or CD154. The
      relationship of TFH cells to the Th2 lineage was confirmed when TFH cells were
      found to develop from CXCR5(-) PD-1(-) IL-4/GFP(+) CD4(+) T cells after their
      transfer into naive mice and antigen challenge in vivo.

PMID- 19380638
TI  - IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are
      T follicular helper cells.
AB  - Interleukin (IL)-4 is the quintessential T helper type 2 (Th2) cytokine produced
      by CD4(+) T cells in response to helminth infection. IL-4 not only promotes the
      differentiation of Th2 cells but is also critical for immunoglobulin (Ig) G1 and
      IgE isotype-switched antibody responses. Despite the IL-4-mediated link between
      Th2 cells and B lymphocytes, the location of IL-4-producing T cells in the lymph
      nodes is currently unclear. Using IL-4 dual reporter mice, we examined the Th2
      response and IL-4 production in the draining mesenteric lymph nodes during
      infection with the enteric nematode Heligmosomoides polygyrus. We show that
      although IL-4-competent Th2 cells are found throughout the B and T cell areas, IL
      4-producing Th2 cells are restricted to the B cell follicles and associate with
      germinal centers. Consistent with their localization, IL-4 producers express high
      levels of CXCR5, ICOS, PD-1, IL-21, and BCL-6, a phenotype characteristic of T
      follicular helper (Tfh) cells. Although IL-4 was dispensable for the generation
      of Th2 and Tfh cells, its deletion resulted in defective B cell expansion and
      maturation. Our report reveals the compartmentalization of Th2 priming and IL-4
      production in the lymph nodes during infection, and identifies Tfh cells as the
      dominant source of IL-4 in vivo.

PMID- 19380639
TI  - TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary
      mediastinal B cell lymphoma.
AB  - Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the
      malignant cells of classical Hodgkin lymphoma (cHL), are dependent on
      constitutive activation of nuclear factor kappaB (NF-kappaB). NF-kappaB
      activation through various stimuli is negatively regulated by the zinc finger
      protein A20. To determine whether A20 contributes to the pathogenesis of cHL, we
      sequenced TNFAIP3, encoding A20, in HL cell lines and laser-microdissected HRS
      cells from cHL biopsies. We detected somatic mutations in 16 out of 36 cHLs
      (44%), including missense mutations in 2 out of 16 Epstein-Barr virus-positive
      (EBV(+)) cHLs and a missense mutation, nonsense mutations, and frameshift-causing
      insertions or deletions in 14 out of 20 EBV(-) cHLs. In most mutated cases, both
      TNFAIP3 alleles were inactivated, including frequent chromosomal deletions of
      TNFAIP3. Reconstitution of wild-type TNFAIP3 in A20-deficient cHL cell lines
      revealed a significant decrease in transcripts of selected NF-kappaB target genes
      and caused cytotoxicity. Extending the mutation analysis to primary mediastinal B
      cell lymphoma (PMBL), another lymphoma with constitutive NF-kappaB activity,
      revealed destructive mutations in 5 out of 14 PMBLs (36%). This report identifies
      TNFAIP3 (A20), a key regulator of NF-kappaB activity, as a novel tumor suppressor
      gene in cHL and PMBL. The significantly higher frequency of TNFAIP3 mutations in
      EBV(-) than EBV(+) cHL suggests complementing functions of TNFAIP3 inactivation
      and EBV infection in cHL pathogenesis.

PMID- 19380642
TI  - Development of an online morbidity, mortality, and near-miss reporting system to
      identify patterns of adverse events in surgical patients.
AB  - OBJECTIVES: To design a Web-based system to track adverse and near-miss events,
      to establish an automated method to identify patterns of events, and to assess
      the adverse event reporting behavior of physicians. DESIGN: A Web-based system
      was designed to collect physician-reported adverse events including weekly
      Morbidity and Mortality (M&M) entries and anonymous adverse/near-miss events. An
      automated system was set up to help identify event patterns. Adverse event
      frequency was compared with hospital databases to assess reporting completeness.
      SETTING: A metropolitan tertiary care center. MAIN OUTCOME MEASURES:
      Identification of adverse event patterns and completeness of reporting. RESULTS:
      From September 2005 to August 2007, 15,524 surgical patients were reported
      including 957 (6.2%) adverse events and 34 (0.2%) anonymous reports. The
      automated pattern recognition system helped identify 4 event patterns from M&M
      reports and 3 patterns from anonymous/near-miss reporting. After
      multidisciplinary meetings and expert reviews, the patterns were addressed with
      educational initiatives, correction of systems issues, and/or intensive quality
      monitoring. Only 25% of complications and 42% of inpatient deaths were reported.
      A total of 75.2% of adverse events resulting in permanent disability or death
      were attributed to the nature of the disease. Interventions to improve reporting
      were largely unsuccessful. CONCLUSIONS: We have developed a user-friendly Web
      based system to track complications and identify patterns of adverse events.
      Underreporting of adverse events and attributing the complication to the nature
      of the disease represent a problem in reporting culture among surgeons at our
      institution. Similar systems should be used by surgery departments, particularly
      those affiliated with teaching hospitals, to identify quality improvement
      opportunities.

PMID- 19380643
TI  - Results of Roux-en-Y gastric bypass in morbidly obese vs superobese patients:
      similar body weight loss, correction of comorbidities, and improvement of quality
      of life.
AB  - HYPOTHESIS: Gastric bypass corrects comorbidities and quality of life similarly
      in superobese (SO) and morbidly obese (MO) patients despite higher residual
      weight in SO patients. DESIGN: Prospective cohort study comparing results of
      primary laparoscopic gastric bypass in MO and SO patients. SETTING: University
      hospital and community hospital with common bariatric programs. PATIENTS: A total
      of 492 MO and 133 SO patients treated consecutively between January 1, 1999, and
      June 30, 2006. INTERVENTION: Primary laparoscopic Roux-en-Y gastric bypass. MAIN
      OUTCOME MEASURES: Operative morbidity, weight loss, residual body mass index
      (BMI) (calculated as weight in kilograms divided by height in meters squared),
      evolution of comorbidities, quality of life, and Bariatric Analysis and Reporting
      Outcome System score. RESULTS: Surgery was longer in SO patients, but operative
      morbidity was similar. The MO patients lost a maximum of 15 BMI units and
      maintained an average loss of 13 BMI units after 6 years, compared with 21 and 17
      in SO patients, which corresponds to a 30.1% and 30.7% total body weight loss,
      respectively. After 6 years, the BMI was less than 35 in more than 90% of MO
      patients but in less than 50% of SO patients. Despite these differences,
      improvements in quality of life and comorbidities were impressive and similar in
      both groups. CONCLUSION: Although many SO patients remain in the severely obese
      or MO category, equivalent improvements in quality of life and obesity-related
      comorbidities indicate that weight loss is not all that matters after bariatric
      surgery.

PMID- 19380644
TI  - Bariatric surgery outcomes at designated centers of excellence vs nondesignated
      programs.
AB  - OBJECTIVE: To compare outcomes of patients undergoing bariatric procedures in
      hospitals designated as centers of excellence compared with nondesignated
      hospitals. DESIGN: The 2005 National Inpatient Survey was used to compare
      outcomes at designated vs nondesignated hospitals. In addition to conventional
      null-hypothesis statistical testing to assess differences, effect sizes were
      calculated to estimate the clinical significance for observed differences.
      RESULTS: Centers of excellence performed substantially more operations than
      nondesignated centers. Despite this, outcomes were equivalent at centers of
      excellence and hospitals without this designation. Volume-outcome modeling
      attempting to identify the optimal number for a minimum volume threshold for
      bariatric operations revealed that annual procedure volume has a weak effect on
      outcomes. Similarly, many variables that were statistically significantly
      different between centers and noncenters proved to be clinically unimportant by
      effect size analysis. Risk adjustment was effectively achieved by using the
      Agency for Healthcare Research and Quality-supplied variables all-payer severity
      adjusted diagnostic related group expected charges and deaths. CONCLUSIONS:
      Designation as a bariatric surgery center of excellence does not ensure better
      outcomes. Neither does high annual procedure volume. Extra expenses associated
      with center of excellence designation may not be warranted.

PMID- 19380645
TI  - Expert consensus vs empirical estimation of injury severity: effect on quality
      measurement in trauma.
AB  - OBJECTIVE: To determine the extent to which the Injury Severity Score (ISS) and
      Trauma Mortality Probability Model (T-MPM), a new trauma injury score based on
      empirical injury severity estimates, agree on hospital quality. DESIGN, SETTING,
      AND PATIENTS: Retrospective cohort study based on 66,214 patients in 68
      hospitals. Four risk-adjustment models based on either ISS or T-MPM were
      constructed, with or without physiologic information. MAIN OUTCOME MEASURES:
      Hospital quality was measured using the ratio of the observed-to-expected
      mortality rates. Pairwise comparisons of hospital quality based on ISSaugmented
      vs T-MPMaugmented were performed using the intraclass correlation coefficient and
      the kappa statistic. RESULTS: There was almost perfect agreement for the ratios
      of the observed to expected mortality rates based on the T-MPM vs the ISS when
      physiologic information was included in the model (intraclass correlation
      coefficient, 0.93). There was substantial agreement on which hospitals were
      identified as high-, intermediate-, and low-quality hospitals (kappa = 0.79).
      Excluding physiologic information decreased the level of agreement between the T
      MPM and the ISS (intraclass correlation coefficient, 0.88 and kappa = 0.58).
      CONCLUSIONS: The choice of expert-based or empirical Abbreviated Injury Score
      severity scores for individual injuries does not seem to have a significant
      effect on hospital quality measurement when physiologic information is included
      in the prediction model. This finding should help to convince all stakeholders
      that the quality of trauma care can be accurately measured and has face validity.

PMID- 19380646
TI  - Contained anastomotic leaks after colorectal surgery: are we too slow to act?
AB  - HYPOTHESIS: Contained and free anastomotic leaks, which occur in a small
      percentage of patients after colorectal surgery, are different clinical entities
      and consequently should be managed differently. DESIGN: Retrospective medical
      record review. SETTING: Academic medical center. PATIENTS: Patients who underwent
      colectomy with primary anastomosis (N = 4019) between January 1, 1992, and
      December 13, 2004, were eligible for participation in the study. Fifty-eight
      patients (1.5%) with an anastomotic leak demonstrated by communication between
      the collection and the gastrointestinal tract were identified. Twenty-eight of
      the patients had free leaks and 30 had contained leaks. MAIN OUTCOME MEASURES:
      Time to presentation, symptoms at presentation, rates of reexploration, and in
      hospital mortality. RESULTS: Baseline characteristics, presenting symptoms,
      physical examination findings, and laboratory values were similar between
      patients with contained and free leaks. Almost all patients with free leaks were
      taken directly to the operating room, whereas those with contained leaks were
      initially more likely to be treated nonoperatively. However, 24 of the 28
      patients with contained leaks (86%) ultimately required surgical intervention. In
      hospital mortality was the same in both groups (18% in the contained leak group
      and 17% in the free leak group). CONCLUSIONS: In patients with contained leaks
      who have documented communication between the abscess cavity and the bowel, there
      is no difference in the rate of operative management or morbidity and mortality
      when compared with those with free leaks. This finding suggests that the
      categorization of leaks as free or contained may not be justified and argues for
      early operative intervention even in patients with contained leaks.

PMID- 19380647
TI  - Long-term survival after surgery for primary hepatic sarcoma in adults.
AB  - HYPOTHESIS: Patients with primary hepatic sarcomas benefit from resection, with
      possible long-term cure. DESIGN: Retrospective and prospective cohort study.
      SETTING: University hospitals of Hamburg-Eppendorf and Dusseldorf, Germany.
      PATIENTS: Between 1985 and 2006, 22 patients (8 men and 14 women; median age at
      initial diagnosis, 54 years [range, 19-80 years]) were surgically treated for
      primary hepatic sarcomas. INTERVENTION: Tumor resection with curative intent
      ranging from nonanatomical resection to liver transplant. MAIN OUTCOME MEASURES:
      Effects on overall survival were analyzed using the log-rank test. RESULTS: The
      majority of tumors were more than 5 cm (n = 19), with a median tumor size of 7 cm
      (range, 4-14 cm); of intermediate differentiation (G2; n = 15); and classified as
      leiomyosarcoma (n = 7). Ten patients received a hemihepatectomy. In 4 patients, a
      bisegmentectomy was performed and in 2 patients, a segmentectomy, while 4
      patients received a nonanatomical resection. Liver transplant was performed in 2
      patients. In 18 patients, complete tumor resection (R0) was achieved.
      Perioperative mortality was 0%. Median follow-up was 88 months (range, 6-246
      months). Local recurrence occurred in 6 patients. Distant metastases were
      diagnosed in 10 patients, predominantly in the lung (n = 6). The 5-year survival
      after surgery was 65%, with 41% of the patients living more than 10 years without
      disease. Patients with angiosarcoma had a poor prognosis (P = .03). CONCLUSIONS:
      Although primary hepatic sarcoma is a rare malignant tumor, no standard treatment
      is established. A long-term survival is possible after complete tumor resection
      in a preselected population with early-stage disease.

PMID- 19380648
TI  - Treatment strategy for intraductal papillary mucinous neoplasm of the pancreas
      based on malignant predictive factors.
AB  - BACKGROUND: Noninvasive intraductal papillary mucinous neoplasms (IPMNs) have a
      favorable prognosis; however, the prognosis of invasive intraductal papillary
      mucinous carcinoma (invasive IPMC) is poor. Identification of predictive factors
      for differentiating IPMC from benign IPMNs would assist in providing appropriate
      treatment. DESIGN: Retrospective study (1999-2006). SETTING: Wakayama Medical
      University Hospital, Wakayama, Japan. PATIENTS: Fifty-four patients with IPMN who
      underwent surgery; histologic examination showed benign adenomas in 29, carcinoma
      in situ in 14, and invasive carcinoma in 11 patients. MAIN OUTCOME MEASURES:
      Clinical data, preoperative imaging findings, cytologic findings, tumor markers
      in serum and pancreatic juice, and overall survival. RESULTS: Age of 70 years or
      older, presence of mural nodules, mural nodule size of 5 mm or larger, and
      carcinoembryonic antigen (CEA) level in pancreatic juice of 110 ng/mL or higher
      (as obtained by preoperative endoscopic retrograde pancreatography) were
      predictive of a malignant IPMN by univariate analysis, and a CEA level of 110
      ng/mL or higher in pancreatic juice was identified as the only independent
      predictive factor for the malignant entity. The presence of jaundice or body
      weight loss, main pancreatic duct type, presence of mural nodules, mural nodule
      size of 5 mm or larger, and CEA level in the pancreatic juice of 110 ng/mL or
      higher were all predictive of invasive IPMCs by univariate analysis. CONCLUSION:
      Measurement of the CEA level in pancreatic juice should be considered in the
      diagnosis of IPMC.

PMID- 19380649
TI  - Influence of overweight on patients with gastric cancer after undergoing curative
      gastrectomy: an analysis of 689 consecutive cases managed by a single center.
AB  - HYPOTHESIS: Overweight (body mass index [calculated as weight in kilograms
      divided by height in meters squared], > or =25.0) has an effect on surgical
      results, postoperative complications, and long-term survival in patients with
      gastric cancer who underwent curative gastrectomy. DESIGN: Retrospective study
      from January 1, 1992, through December 31, 2002. SETTING: Wakayama Medical
      University Hospital. PATIENTS: This study included 689 patients who underwent
      curative gastrectomy (R0). Patients who underwent laparoscopic gastrectomy,
      gastrectomy with pancreaticoduodenectomy, gastrectomy with another organ
      resection (liver, colon, or ovary), or gastrectomy with thoracotomy were not
      included. MAIN OUTCOME MEASURES: Duration of operation, amount of blood loss,
      incidence of postoperative complications, and survival analysis. RESULTS: The
      mean (SD) duration of the operation was longer in the overweight group (315 [75]
      minutes) than in the normal-weight group (277 [85] minutes) (P < .001). The mean
      (SD) intraoperative blood loss was larger in the overweight group (882 [764] mL)
      than in the normal-weight group (536 [410] mL) (P < .001). The rates of
      postoperative complications (anastomotic leakage, pancreatic fistula, and intra
      abdominal abscess) were significantly higher in the overweight group (P < .05).
      Multivariate logistic regression analysis identified that postoperative
      complications were significantly associated with being overweight (P = .01) and
      with undergoing pancreatectomy (P = .03). Disease-specific and overall survival
      did not show any significant difference between the 2 groups. CONCLUSIONS: Being
      overweight is not a poor risk factor for survival in patients with gastric
      cancer, although it is independently predictive of postoperative complications.

PMID- 19380650
TI  - Perioperative supplemental oxygen therapy and surgical site infection: a meta
      analysis of randomized controlled trials.
AB  - OBJECTIVE: To conduct a meta-analysis of randomized controlled trials in which
      high inspired oxygen concentrations were compared with standard concentrations to
      assess the effect on the development of surgical site infections (SSIs). DATA
      SOURCES: A systematic literature search was conducted using the MEDLINE, EMBASE,
      and Cochrane databases and included a manual search of references of original
      articles, poster presentations, and abstracts from major meetings ("gray"
      literature). STUDY SELECTION: Twenty-one of 2167 articles met the inclusion
      criteria. Of these, 5 randomized controlled trials (3001 patients) assessed the
      effect of perioperative supplemental oxygen use on the SSI rate. Studies used a
      treatment-inspired oxygen concentration of 80%. Maximum follow-up was 30 days.
      DATA EXTRACTION: Data were abstracted by 3 independent reviewers using a
      standardized data collection form. Relative risks were reported using a fixed
      effects model. Results were subjected to publication bias testing and sensitivity
      analyses. DATA SYNTHESIS: Infection rates were 12.0% in the control group and
      9.0% in the hyperoxic group, with relative risk reduction of 25.3% (95%
      confidence interval [CI], 8.1%-40.1%) and absolute risk reduction of 3.0% (1.1%
      5.3%). The overall risk ratio was 0.742 (95% CI, 0.599-0.919; P = .006). The
      benefit from increasing oxygen concentration was greater in colorectal-specific
      procedures, with a risk ratio of 0.556 (95% CI, 0.383-0.808; P = .002).
      CONCLUSIONS: Perioperative supplemental oxygen therapy exerts a significant
      beneficial effect in the prevention of SSIs. We recommend its use along with
      maintenance of normothermia, meticulous glycemic control, and preservation of
      intravascular volume perioperatively in the prevention of SSIs.

PMID- 19380651
TI  - Completion pancreatectomy for treatment of a Clostridium perfringens pancreatic
      infection.
AB  - Pancreatic infection is associated with high morbidity and mortality. Drainage of
      the infection is the usual therapeutic approach. Clostridium perfringens
      infection can cause fulminant sepsis, but it rarely occurs within the pancreas.
      The case of a 76-year-old man with cystic pancreatic lesions in which sepsis
      developed after endoscopic ultrasound with fine-needle aspiration biopsy is
      described. The sepsis was managed with pancreatic resection and antibiotics.
      Clostridium perfringens was isolated from blood cultures and microbiologic smears
      from the pancreas. Invasive intraductal papillary mucinous neoplasm with lymph
      node involvement was identified on histologic examination. The patient made a
      complete recovery from surgery without complications.

PMID- 19380652
TI  - Stress and burnout among surgeons: understanding and managing the syndrome and
      avoiding the adverse consequences.

PMID- 19380653
TI  - Image of the month. Wermer syndrome and Zollinger-Ellison syndrome.

PMID- 19380654
TI  - Image of the month. Gastrointestinal stromal tumor of the small bowel.

PMID- 19380655
TI  - Fluorescent cholangiography using indocyanine green for laparoscopic
      cholecystectomy: an initial experience.

PMID- 19380656
TI  - Asymptomatic carotid stenosis: criterion standard should be medical therapy.

PMID- 19380657
TI  - Sham-feed or sham?

PMID- 19380658
TI  - Chronic ulcers caused by injection of substances: healing aided by naltrexone.

PMID- 19380659
TI  - Psoriasis and the risk of diabetes and hypertension: a prospective study of US
      female nurses.
AB  - OBJECTIVE: To evaluate the independent association between psoriasis and risk of
      diabetes and hypertension. DESIGN: A prospective study of female nurses who were
      followed up from 1991 to 2005. SETTING: Nurses' Health Study II, a cohort of 116
      671 US women aged 27 to 44 years in 1991. PARTICIPANTS: The study included 78 061
      women who responded to a question about a lifetime history of physician-diagnosed
      psoriasis in 2005. Women who reported a diagnosis of diabetes or hypertension at
      baseline were excluded. Main Outcome Measure New diagnosis of diabetes or
      hypertension, obtained from biennial questionnaires. RESULTS: Of the 78 061
      women, 1813 (2.3%) reported a diagnosis of psoriasis. During the 14 years of
      follow-up, a total of 1560 incident cases (2%) of diabetes and 15 724 incident
      cases (20%) of hypertension were documented. The multivariate-adjusted relative
      risk of diabetes in women with psoriasis compared with women without psoriasis
      was 1.63 (95% confidence interval, 1.25-2.12). Women with psoriasis were also at
      an increased risk for the development of hypertension (multivariate relative
      risk, 1.17; 95% confidence interval, 1.06-1.30). Age, body mass index, and
      smoking status did not significantly modify the association between psoriasis and
      risk of diabetes or hypertension (P values for interaction, > or =.07).
      CONCLUSIONS: In this prospective analysis, psoriasis was independently associated
      with an increased risk of diabetes and hypertension. Future studies are needed to
      find out whether psoriasis treatment will reduce the risk of diabetes and
      hypertension.

PMID- 19380660
TI  - Efficacy and safety of combination Acitretin and Pioglitazone therapy in patients
      with moderate to severe chronic plaque-type psoriasis: a randomized, double
      blind, placebo-controlled clinical trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of combination therapy with
      acitretin and pioglitazone hydrochloride in patients with moderate to severe
      chronic plaque-type psoriasis. DESIGN: Randomized, double-blind, placebo
      controlled clinical trial. SETTING: A tertiary care referral hospital. Patients
      The study included patients of either sex (age range, 18-65 years) with moderate
      to severe chronic plaque-type psoriasis. Patients were excluded if they were of
      child-bearing potential or if they had impaired liver or renal function,
      hyperlipidemia, diabetes mellitus, coronary artery disease, or a body mass index
      greater than 30 (calculated as weight in kilograms divided by height in meters
      squared). Of the 62 patients screened, 41 were randomly assigned to 2 groups: 22
      to an acitretin (25 mg) plus placebo group and 19 to an acitretin (25 mg) plus
      pioglitazone hydrochloride (15 mg) group. Main Outcome Measure Change in
      Psoriasis Area and Severity Index score between the 2 groups from baseline to 12
      weeks. RESULTS: After 12 weeks of therapy, the percentage of reduction in the
      Psoriasis Area and Severity Index score was 64.2% in the acitretin plus
      pioglitazone group and 51.7% in the acitretin plus placebo group. The majority of
      the adverse events were mild to moderate except for 1 possibly unrelated episode
      of acute myocardial infarction in a 49-year-old woman in the acitretin plus
      placebo group. CONCLUSIONS: Pioglitazone has a potential beneficial antipsoriatic
      effect and may provide a convenient, efficacious, and relatively safe option to
      combine with acitretin, although further studies are needed. Trial Registration
      clinicaltrials.gov Identifier: NCT00395941.

PMID- 19380661
TI  - Melanoma in middle-aged and older men: a multi-institutional survey study of
      factors related to tumor thickness.
AB  - OBJECTIVES: To identify factors related to the detection of melanoma and to
      determine those that differ between thinner vs thicker tumors in middle-aged and
      older men. DESIGN: Survey. SETTING: Three institutional melanoma clinics.
      PARTICIPANTS: Men 40 years or older who had newly diagnosed invasive melanoma.
      MAIN OUTCOME MEASURES: Differences in melanoma awareness, skin examination
      practices, discovery patterns, and social/medical care factors relative to tumor
      thickness. RESULTS: Two hundred twenty-seven men completed surveys within 3
      months of melanoma diagnosis; 57 (25.1%) had thicker tumors (>2.00 mm). Thicker
      tumors were associated with nodular histologic features (43.9%), a lack of
      atypical nevi, having less than a high school education, and patient vs physician
      (dermatologist or nondermatologist) detection. Knowledge of melanoma (P = .007),
      attention to skin cancer detection information (P = .02), an interest in health
      topics (P = .003), and knowing the importance of physician skin examination (P =
      .05) were more common in those with thin tumors. Tumor thickness did not
      correlate with age, anatomic location, marital/cohabitation status, prior skin
      cancer, or sun sensitivity. Overall patient awareness of melanoma warning signs,
      skin self-examination practices, and Internet use were poor (<20%, <50%, and
      <14%, respectively). CONCLUSIONS: Physician discovery, the patient's higher level
      of education and detection-promoting awareness and attitudes, and the presence of
      clinically atypical nevi were related to thinner melanomas. Innovative outreach
      strategies and novel educational campaigns incorporating these factors, coupled
      with sharper messages regarding the importance of physician screening, are needed
      to improve early detection in middle-aged and older men.

PMID- 19380662
TI  - Factors associated with physician discovery of early melanoma in middle-aged and
      older men.
AB  - OBJECTIVE: To determine factors associated with physician discovery of early
      melanoma in middle-aged and older men. DESIGN: Survey. SETTING: Three
      institutional melanoma clinics. PARTICIPANTS: A total of 227 male participants
      (aged > or =40 years) with invasive melanoma who completed surveys within 3
      months of diagnosis. Intervention Survey. MAIN OUTCOME MEASURES: Factors
      associated with physician-detected thin melanoma. RESULTS: Patients with
      physician-detected melanoma were older, 57% were 65 years or older compared with
      34% for other-detected (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.19
      5.55) and 42% for patient-detected melanoma (P = .07). Physician-detected
      melanoma in the oldest patients (aged > or =65 years) had tumor thickness equal
      to that of self-detected melanoma or melanoma detected by other means in younger
      patients. Back lesions composed 46% of all physician-detected melanoma, 57% of
      those detected by other means, and 16% of self-detected lesions (physician- vs
      self-detected: OR, 4.25; 95% CI, 1.96-9.23). Ninety-two percent of all physician
      detected back-of-the-body melanomas were smaller than 2 mm compared with 63% of
      self-detected lesions (P = .004) and 76% of lesions detected by other means (P =
      .07). CONCLUSIONS: Skin screenings of at-risk middle-aged and older American men
      can be integrated into the routine physical examination, with particular emphasis
      on hard-to-see areas, such as the back of the body. "Watch your back"
      professional education campaigns should be promoted by skin cancer advocacy
      organizations.

PMID- 19380663
TI  - Risk factors in elderly people for lentigo maligna compared with other melanomas:
      a double case-control study.
AB  - OBJECTIVE: To assess lentigo maligna (LM) as an epidemiological entity separate
      from other melanomas (OMs) in elderly people. DESIGN: Double age- and sex-matched
      case-control study to compare the risk factors for LMs and OMs. SETTING: General
      community. Patients A total of 76 patients with LM were paired by age and sex
      with 76 patients with OMs and 152 controls. MAIN OUTCOME MEASURES: The
      association of melanoma risk with the following potential risk factors: sun
      exposure history by 10-year periods, frequency of sunburns, phenotypic traits,
      density of freckles and sun sensitivity at age 20 years, counts of nevi larger
      than 2 mm in diameter on the face and forearm, skin aging features (as assessed
      using a photographic scale), and history of basal and/or squamous cell
      carcinomas. RESULTS: Risk of LMs and OMs were similarly associated with history
      of sunburns, light skin type, and freckling. Cumulative chronic outdoor and
      occupational sun exposures were not risk factors in any of the 2 groups of
      melanomas. Lentigo maligna differed from OMs by the absence of a detectable
      association with the number of nevi and a greater association with nonmelanoma
      skin cancers. CONCLUSIONS: Although chronically sun-exposed skin is a
      prerequisite for LM, risk of LM does not increase with the cumulative dose of sun
      exposure, but LM is associated with sunburn history, like all other types of
      melanomas. The main epidemiological characteristic of LM is the absence of an
      apparent relation with the genetic propensity to develop nevi. This
      epidemiological profile is in accordance with recent molecular findings and may
      also account for the histoclinical and evolutive characteristics of LM.

PMID- 19380665
TI  - Treatment of refractory ulcerative necrobiosis lipoidica diabeticorum with
      infliximab: report of a case.
AB  - BACKGROUND: Necrobiosis lipoidica diabeticorum (NLD) is a rare, granulomatous
      inflammatory skin disease of unknown origin, sometimes associated with diabetes
      mellitus. Skin lesions usually develop on the lower extremities and can progress
      toward ulceration and scarring. Many treatments have been proposed, but few have
      demonstrated consistent efficacy, and no standard regimens have emerged to date.
      OBSERVATIONS: An 84-year-old woman with type 1 diabetes mellitus presented with a
      3-year history of chronic right-lower-extremity erythematous papules and plaques
      that had developed into confluent ulcers with prominent granulation tissue and an
      orange-yellow hue. The results of a biopsy of the lesion was consistent with a
      diagnosis of NLD. The wound did not respond to 4 months of intensive local wound
      care. After the first intravenous infusion of infliximab (5 mg/kg), there was
      rapid reduction in wound size, pain, and drainage. There was complete wound
      healing with excellent cosmesis at 6 weeks (total of 3 infusions). CONCLUSIONS:
      Infliximab should be considered in the treatment of refractory, ulcerative NLD.
      Its anti-tumor necrosis factor activity may underlie its efficacy in targeting
      this granulomatous process, and further investigation should be undertaken to
      confirm these results.

PMID- 19380664
TI  - Acral lentiginous melanoma: incidence and survival patterns in the United States,
      1986-2005.
AB  - OBJECTIVE: To examine incidence and survival patterns of acral lentiginous
      melanoma (ALM) in the United States. DESIGN: Population-based registry study. We
      used the Surveillance, Epidemiology, and End Results (SEER) Program of the
      National Cancer Institute to evaluate data from 17 population-based cancer
      registries from 1986 to 2005. PARTICIPANTS: A total 1413 subjects with
      histologically confirmed cases of ALM. Main Outcome Measure Incidence and
      survival patterns of patients with ALM. RESULTS: The age-adjusted incidence rate
      of ALM overall was 1.8 per million person-years. The proportion of ALM among all
      melanoma subtypes was greatest in blacks (36%). Acral lentiginous melanoma had 5-
      and 10-year melanoma-specific survival rates of 80.3% and 67.5%, respectively,
      which were less than those for all cutaneous malignant melanomas overall (91.3%
      and 87.5%, respectively; P < .001). The ALM 5- and 10-year melanoma-specific
      survival rates were highest in non-Hispanic whites (82.6% and 69.4%),
      intermediate in blacks (77.2% and 71.5%), and lowest in Hispanic whites (72.8%
      and 57.3%) and Asian/Pacific Islanders (70.2% and 54.1%). Acral lentiginous
      melanoma thickness and stage correlated with survival according to sex and in the
      different racial groups. CONCLUSIONS: Population-based data showed that ALM is a
      rare melanoma subtype, although its proportion among all melanomas is higher in
      people of color. It is associated with a worse prognosis than cutaneous malignant
      melanoma overall. Hispanic whites and Asian/Pacific Islanders have worse survival
      rates than other groups, and factors such as increased tumor thickness and more
      advanced stage at presentation are the most likely explanations.

PMID- 19380666
TI  - alpha-Melanocyte-stimulating hormone-induced eruptive nevi.
AB  - BACKGROUND: Synthetic peptides that target proopiomelanocortin receptors are
      being investigated as a novel and safe way to tan. It has been postulated that
      synthetic alpha-melanocyte-stimulating hormone (alpha-MSH) peptides may have
      protective effects against the development of melanoma because of their
      melanogenic activity. Their ultimate biological effect, however, especially in
      patients with dysplastic nevi or previous melanoma, has yet to be determined.
      OBSERVATIONS: A 40-year-old white man with a history of melanoma and multiple
      dysplastic nevi self-administered synthetic alpha-MSH. He developed crops of new
      pigmented nevi, many of which had atypical clinical and histopathologic features.
      The preexisting nevi became darker and acquired growth features. After alpha-MSH
      use was discontinued, the nevi progressively lightened and lost their growth
      features. CONCLUSIONS: Synthetic alpha-MSH peptides can drive proliferation of
      neoplastic melanocytic cells in predisposed patients. This could present an
      increased risk for melanoma development.

PMID- 19380667
TI  - Occurrence of nonmelanoma skin cancers on the hands after UV nail light exposure.
AB  - BACKGROUND: Exposure to tanning beds, which contain mostly high-dose UV-A
      emitters, is a known cause of photoaging. Evidence is also accumulating for an
      association between tanning bed use and the development of skin cancer. Another
      source of high-dose UV-A is UV nail lights, available for use in the home and in
      beauty salons. OBSERVATIONS: Two healthy middle-aged women with no personal or
      family history of skin cancer developed nonmelanoma skin cancers on the dorsum of
      their hands. Both women report previous exposure to UV nail lights. CONCLUSIONS:
      It appears that exposure to UV nail lights is a risk factor for the development
      of skin cancer; however, this observation warrants further investigation. In
      addition, awareness of this possible association may help physicians identify
      more skin cancers and better educate their patients.

PMID- 19380668
TI  - Calciphylaxis with normal renal and parathyroid function: not as rare as
      previously believed.
AB  - BACKGROUND: Calciphylaxis is a life-threatening form of metastatic calcification
      induced microvascular occlusion syndrome. Although traditionally observed in
      patients with end-stage renal disease and/or hyperparathyroidism, the development
      of calciphylaxis in "nontraditional" patients having both normal renal and
      parathyroid function has been reported. However, to date there has been no
      collective analysis identifying common patient characteristics potentially
      predisposing to the development of calciphylaxis in nontraditional patients.
      OBSERVATIONS: A 58-year-old woman with endometrial carcinoma developed extensive
      calciphylaxis despite the presence of normal renal and parathyroid function. The
      disease resolved with rapid diagnosis, supportive therapy, and medical
      management. Analysis of this case and the 13 previously reported cases of
      nontraditional calciphylaxis identified the following patient characteristics
      that highlight clinical situations potentially predisposing to calciphylaxis:
      hypoalbuminemia, malignant neoplasm, systemic corticosteroid use, anticoagulation
      with warfarin sodium or phenprocoumon, chemotherapy, systemic inflammation,
      hepatic cirrhosis, protein C or S deficiency, obesity, rapid weight loss, and
      infection. CONCLUSIONS: Calciphylaxis is becoming increasingly common in patients
      with normal renal and parathyroid function. The observations from this study may
      assist dermatologists in the rapid diagnosis and prompt initiation of therapy for
      this devastating disease.

PMID- 19380669
TI  - Psoriasis bench to bedside: genetics meets immunology.

PMID- 19380670
TI  - Dermatologic comorbidities of diabetes mellitus and related issues.

PMID- 19380672
TI  - Use of genetic tools to control tumor margins in melanoma.

PMID- 19380671
TI  - Engaging patients and their partners in preventive health behaviors: the
      physician factor.

PMID- 19380673
TI  - Tender papule of the nail fold--quiz case.

PMID- 19380674
TI  - Agminated papules and pustules on the flank--quiz case.

PMID- 19380675
TI  - Recurrent hypertrophic nodules on the bilateral arms--quiz case.

PMID- 19380676
TI  - Follicular spicules of the nose and ears--quiz case.

PMID- 19380677
TI  - Neuropathy and gait disturbances in patients with venous disease: a pilot study.

PMID- 19380678
TI  - Preventing diabetic skin ulcers in Latinos--no small feat: development of a
      Spanish and English survey for fast assessment of lower extremity skin care
      practices.

PMID- 19380679
TI  - Gender differences in melanoma awareness and detection practices between middle
      aged and older men with melanoma and their female spouses.

PMID- 19380680
TI  - Ulcers related to acupuncture and traditional chinese medicine: a case series and
      review of the literature.

PMID- 19380681
TI  - HAIR-AN syndrome in a male adolescent with concomitant vitiligo.

PMID- 19380682
TI  - Remission of extensive merkel cell carcinoma after electrochemotherapy.

PMID- 19380683
TI  - Cole disease: guttate hypopigmentation and punctate palmoplantar keratoderma.

PMID- 19380684
TI  - Annular blisters on the arm.

PMID- 19380685
TI  - Blepharochalasis: a rare condition misdiagnosed as recurrent angioedema.

PMID- 19380686
TI  - Localized contact urticaria caused by lidocaine/tetracaine peel.

PMID- 19380687
TI  - Treatment of delusional parasitosis with aripiprazole.

PMID- 19380688
TI  - Immediate diagnosis of cryptococcus fungal infection using touch preparation
      analysis.

PMID- 19380689
TI  - Dermoscopy of Cowden syndrome.

PMID- 19380690
TI  - T1 hyperintense renal lesions: characterization with diffusion-weighted MR
      imaging versus contrast-enhanced MR imaging.
AB  - PURPOSE: To compare the performance of apparent diffusion coefficient (ADC)
      measurement obtained with diffusion-weighted (DW) magnetic resonance (MR) imaging
      in the characterization of non-fat-containing T1 hyperintense renal lesions with
      that of contrast material-enhanced MR imaging, with histopathologic analysis and
      follow-up imaging as the reference standards. MATERIALS AND METHODS:
      Institutional review board approval was obtained for this HIPAA-compliant
      retrospective study, and the informed consent requirement was waived. Two
      independent observers retrospectively assessed MR images obtained in 41 patients
      with non-fat-containing T1 hyperintense renal lesions. The MR examination
      included acquisition of DW and contrast-enhanced T1-weighted images. For each
      index lesion, the observers assessed the (a) mean (+/- standard deviation) of
      ADC, (b) enhancement ratio, and (c) subtracted images for the presence of
      enhancement (confidence score, 1-5). Histopathologic analysis of renal cell
      carcinomas (RCCs) and follow-up imaging for benign lesions were the reference
      standards. ADCs of benign lesions and RCCs were compared. Receiver operating
      characteristic (ROC) curve analysis was performed to assess the accuracy of DW
      imaging, enhancement ratio, and subtraction for the diagnosis of RCC. RESULTS: A
      total of 64 lesions (mean diameter, 3.9 cm), including 38 benign T1 hyperintense
      cysts and 26 RCCs, were assessed. Mean ADCs of RCCs were significantly lower than
      those of benign cysts ([1.75 +/- 0.57] x 10(-3) mm(2)/sec vs [2.50 +/- 0.53] x
      10(-3) mm(2)/sec, P < .0001). ADCs of solid and cystic portions of complex cystic
      RCCs were significantly different ([1.37 +/- 0.55] x 10(-3) mm(2)/sec vs [2.45 +/
      0.63] x 10(-3) mm(2)/sec, P < .0001). When data from both observers were pooled,
      area under the ROC curve, sensitivity, and specificity were 0.846, 71%, and 91%,
      respectively, for DW imaging; 0.865, 65%, and 96%, respectively, for enhancement
      ratio (at the excretory phase); and 0.861, 83%, and 89%, respectively, for
      subtraction (P = .48 and P = .85, respectively). The combination of DW imaging
      and subtraction resulted in area under the ROC curve, sensitivity, and
      specificity of 0.893, 87%, and 92%, respectively, with significantly improved
      reader confidence compared with subtraction alone (P = .041). CONCLUSION: The
      performance of DW imaging was equivalent to that of enhancement ratio in the
      characterization of T1 hyperintense renal lesions, with both methods having lower
      sensitivity than image subtraction without reaching significance.

PMID- 19380691
TI  - Vertebral fracture assessment in supine position: comparison by using
      conventional semiquantitative radiography and visual radiography.
AB  - PURPOSE: To retrospectively evaluate the accuracy of vertebral fracture
      assessment (VFA) performed with the patient in the supine position and
      conventional semiquantitative radiography of the spine by using conventional
      visual radiography of the spine as the reference standard. MATERIALS AND METHODS:
      This retrospective study was approved by the institutional ethics review board;
      informed consent was obtained from the patients. A total of 250 consecutive
      patients (mean age, 62.0 years; range, 25-89 years) consisting of 190 women (mean
      age, 64 years; range, 25-89 years) and 60 men (mean age, 57.0 years; range, 27-83
      years) who were suspected of having osteoporosis and who underwent VFA in the
      supine position and radiography of the spine were evaluated. VFA and
      semiquantitative radiography were analyzed by using a six-marker point method to
      describe the shape and deformity of each vertebra. Visual radiography of the
      lateral spine was performed by an experienced radiologist. The agreement between
      VFA, visual radiography, and semiquantitative radiography of semiquantitative
      graded fractures was assessed by using weighted kappa statistics. RESULTS: Visual
      radiography helped identify 92 (36.8%) patients with at least one vertebral
      fracture (mean, 1.8 per patient). Most fractures were present in T7, T12, and L1.
      Excellent agreement was found between VFA and visual radiography, with 97.5%
      concordance and kappa = 0.82; VFA and semiquantitative radiography were in
      agreement in 97.4% of patients, with kappa = 0.83; and visual radiography and
      semiquantitative radiography were in agreement in 98.1%, with kappa = 0.87.
      Sensitivity, specificity, and positive and negative predictive values calculated
      by lesion level for VFA compared with visual assessment were 83.6%, 99.1%, 84.1%,
      and 99.1%, respectively. CONCLUSION: VFA performed with patients in the supine
      position is an accurate method to help detect vertebral fractures when compared
      with conventional spine radiography. VFA permits combination of fracture
      assessment with bone mineral density measurement in a single session.

PMID- 19380692
TI  - Pulmonary nodules: volume repeatability at multidetector CT lung cancer
      screening.
AB  - PURPOSE: To assess in vivo volumetric repeatability of an automated software
      algorithm in pulmonary nodules detected during a lung cancer screening trial.
      MATERIALS AND METHODS: This study was approved by an institutional review board.
      Written informed consent was obtained from all participants. Data were collected
      from the Multicentric Italian Lung Detection project, a randomized controlled
      lung cancer screening trial. The first 1236 consecutive baseline computed
      tomographic (CT) studies performed at the Istituto Nazionale Tumori of Milan were
      evaluated. Among the enrolled participants, those who underwent repeat low-dose
      CT after 3 months and had at least one indeterminate nodule with a volume of more
      than 60 mm(3) (diameter of 4.8 mm or greater) were considered. Nonsolid, part
      solid, and pleural-based nodules were excluded from this study. A descriptive
      analysis was performed by calculating means and standard deviations of nodule
      volumes at three assessment times (at baseline and 3 and 12 months later). The
      volume measurement repeatability was determined by using the approach described
      by Bland and Altman. RESULTS: One hundred one subjects (70 men, 31 women; mean
      age, 58 years) with 233 eligible nodules (mean volume, 98.3 mm(3); range, 5-869
      mm(3)) were identified. The 95% confidence interval for difference in measured
      volumes was in the range of +/-27%. About 70% of measurements had a relative
      difference in nodule volume of less than 10%. No malignant lesions were
      registered during the follow-up of these subjects. CONCLUSION: Semiautomatic
      volumetry is sufficiently accurate and repeatable and may be useful in assisting
      with lung nodule management in a lung cancer screening program.

PMID- 19380693
TI  - Comparison of 1.0-T extremity MR and 1.5-T conventional high-field-Strength MR in
      patients with rheumatoid arthritis.
AB  - PURPOSE: To prospectively determine the comparability of 1.0-T extremity magnetic
      resonance (MR) imaging and 1.5-T conventional MR for the evaluation of the hand
      and wrist in assessment of patients with rheumatoid arthritis (RA). MATERIALS AND
      METHODS: Institutional ethics approval and written informed consent were
      obtained. Thirty-two patients (30 women, two men; mean age, 52 years) with RA
      twice underwent MR of either the most symptomatic hand (n = 21) or wrist (n =
      11), once performed with a 1.0-T extremity MR system and once with a 1.5-T
      conventional MR system. The MR examinations were independently assessed by two
      radiologists blinded to imaging platform and patient clinical information for
      erosions, synovitis, and bone marrow edema (BME), according to the Rheumatoid
      Arthritis MR Imaging Score (RAMRIS). One radiologist reevaluated all cases a
      second time to determine the intraobserver variability for each system. Patient
      comfort was assessed with a questionnaire. Intraclass correlation coefficients
      (ICCs) and smallest detectable differences (SDDs) were measured. RESULTS: ICCs
      for intermachine agreement were 0.97-0.99 for erosions, 0.88-0.97 for synovitis,
      and 0.98-0.99 for BME for both readers. The SDDs between the two systems,
      expressed as a percentage of the maximum score, ranged from 3.3% to 12.2% for
      erosions, from 7.4% to 14.8% for synovitis, and from 5% to 9.9% for BME for both
      readers. ICCs for interreader agreement ranged from 0.69 to 0.99 and for
      intrareader agreement, from 0.88 to 0.99. There were substantial differences in
      the subjective patient assessment of confinement, system noise, and difficulty
      with immobilization, and 95.8% of patients preferred examinations performed with
      extremity MR. CONCLUSION: The 1.0-T extremity MR system demonstrates synovial and
      osseous changes in RA equally as well as a 1.5-T conventional MR system and is
      preferred by patients.

PMID- 19380694
TI  - Clinical reasoning: a 62-year-old woman with deafness, unilateral visual loss,
      and episodes of numbness.

PMID- 19380695
TI  - Teaching NeuroImages: diaschisis: is it always reversible?

PMID- 19380697
TI  - Spinocerebellar ataxia type 17 mutation as a causative and susceptibility gene in
      parkinsonism.
AB  - OBJECTIVE: To investigate the role of spinocerebellar ataxia type 17 (SCA17) in
      the development of parkinsonism. METHOD: We screened 1,155 parkinsonian patients
      (931 with Parkinson disease and 224 with multiple system atrophy) and 400 normal
      subjects for SCA17. 99mTc-TRODAT-1 SPECT was used to evaluate the striatal
      dopamine transporter (DAT) status. RESULTS: Trinucleotide expansion in the SCA17
      gene was found in 10 parkinsonian patients (8 with Parkinson disease, 2 with
      multiple system atrophy) using 42 repeats as an upper normal limit. The repeat
      sizes in the patients ranged from 43 to 46, which are considered to be low-range
      expansions. All patients had interrupted sequences. Three probands and three
      asymptomatic carriers underwent 99mTc-TRODAT-1 SPECT. Striatal DAT binding was
      markedly reduced in all probands and mildly decreased in one asymptomatic
      carrier. Among the 400 normal control subjects, there was one individual with an
      expansion of 44 repeats, another with 43 repeats, and two with 42 repeats.
      Striatal DAT binding was decreased not only in the control subjects with 44 or 43
      repeats, but in ones with 42 repeats, suggesting that an expansion as low as 42
      repeats might constitute a susceptibility gene for parkinsonism. CONCLUSIONS: Low
      range expansion of the SCA17 gene is not a rare genetic cause of parkinsonism
      without ataxia in our population. Reduced penetrance or variable expressivity in
      low-range expansion might be an explanation for the blurred cutoff point for
      normal expansion in SCA17.

PMID- 19380698
TI  - Striatal [11C]dihydrotetrabenazine and [11C]methylphenidate binding in Tourette
      syndrome.
AB  - OBJECTIVE: Tourette syndrome (TS) is a common neurodevelopmental disorder marked
      by tics and behavioral comorbidities. Clinical pharmacology suggests that
      dopaminergic signaling abnormalities are part of the pathophysiology of TS. Prior
      molecular imaging studies of nigrostriatal dopaminergic terminal markers report
      conflicting results. Our goal was to characterize the distribution of
      nigrostriatal dopaminergic terminals in subjects with TS. METHODS: Thirty-three
      adult subjects with TS were studied with PET using [11C]dihydrotetrabenazine
      (DTBZ), a ligand for the type 2 vesicular monoamine transporter, and with [11C]
      methylphenidate (MP), a ligand for the plasmalemmal dopamine transporter.
      Subjects were characterized with standard rating instruments for tic severity,
      obsessive-compulsive behaviors, and attentional deficits. RESULTS: We found no
      differences between subjects with TS and control subjects in DTBZ and MP binding
      in any striatal region. There was no correlation between binding measures and
      clinical variables. Ventral striatal DTBZ and MP binding distributions in
      subjects with TS were normal. CONCLUSIONS: We found no evidence of increased
      striatal dopaminergic innervation in Tourette syndrome (TS). Discrepancy between
      our present results and those of other studies may be explained by heterogeneity
      of TS.

PMID- 19380699
TI  - Severity of leukoaraiosis correlates with clinical outcome after ischemic stroke.
AB  - BACKGROUND: Leukoaraiosis (LA) is closely associated with aging, a major
      determinant of clinical outcome after ischemic stroke. In this study we sought to
      identify whether LA, independent of advancing age, affects outcome after acute
      ischemic stroke. METHODS: LA volume was quantified in 240 patients with ischemic
      stroke and MRI within 24 hours of symptom onset. We explored the relationship
      between LA volume at admission and clinical outcome at 6 months, as assessed by
      the modified Rankin Scale (mRS). An ordinal logistic regression model was
      developed to analyze the independent effect of LA volume on clinical outcome.
      RESULTS: Bivariate analyses showed a significant correlation between LA volume
      and mRS at 6 months (r = 0.19, p = 0.003). Mean mRS was 1.7 +/- 1.8 among those
      in the lowest (< or =1.2 mL) and 2.5 +/- 1.9 in the highest (>9.9 mL) quartiles
      of LA volume (p = 0.01). The unfavorable prognostic effect of LA volume on
      clinical outcome was retained in the multivariable model (p = 0.002), which
      included age, gender, stroke risk factors (hypertension, diabetes mellitus,
      atrial fibrillation), previous history of brain infarction, admission plasma
      glucose level, admission NIH Stroke Scale score, IV rtPA treatment, and acute
      infarct volume on MRI as covariates. CONCLUSIONS: The volume of leukoaraiosis is
      a predictor of clinical outcome after ischemic stroke and this relationship
      persists after adjustment for important prognostic factors including age, initial
      stroke severity, and infarct volume.

PMID- 19380700
TI  - Age-associated leukoaraiosis and cortical cholinergic deafferentation.
AB  - OBJECTIVE: To investigate the relationship between age-associated MRI
      leukoaraiosis or white matter hyperintensities (WMH) and cortical
      acetylcholinesterase (AChE) activity. BACKGROUND: One possible mechanism of
      cognitive decline in elderly individuals with leukoaraiosis is disruption of
      cholinergic fibers by strategically located white matter lesions. Periventricular
      lesions may have a higher chance of disrupting cholinergic projections compared
      with more superficial nonperiventricular white matter lesions because of anatomic
      proximity to the major cholinergic axonal projection bundles that originate from
      the basal forebrain. METHODS: Community-dwelling, middle-aged and elderly
      subjects without dementia (mean age 71.0 +/- 9.2 years; 55-84 years; n = 18)
      underwent brain MRI and AChE PET imaging. The severity of periventricular and
      nonperiventricular WMH on fluid-attenuated inversion recovery MRI images was
      scored using the semiquantitative rating scale of Scheltens et al. [11C]methyl-4
      piperidinyl propionate AChE PET imaging was used to assess cortical AChE
      activity. Age-corrected Spearman partial rank correlation coefficients were
      calculated. RESULTS: The severity of periventricular (R = -0.52, p = 0.04) but
      not nonperiventricular (R = -0.20, not significant) WMH was inversely related to
      global cortical AChE activity. Regional cortical cholinergic effects of
      periventricular WMH were most significant for the occipital lobe (R = -0.58, p =
      0.02). CONCLUSIONS: The presence of periventricular but not nonperiventricular
      white matter hyperintensities (WMH) is significantly associated with lower
      cortical cholinergic activity. These findings support a regionally specific
      disruption of cholinergic projection fibers by WMH.

PMID- 19380701
TI  - Horizontal head impulse test detects gentamicin vestibulotoxicity.
AB  - BACKGROUND: Parenteral antibiotic therapy with gentamicin, even in accepted
      therapeutic doses, can occasionally cause bilateral vestibular loss (BVL) due to
      hair cell toxicity. OBJECTIVE: To quantify in patients with gentamicin
      vestibulotoxicity (GVT) the extent of acceleration gain deficit of the horizontal
      vestibulo-ocular reflex at different accelerations with a graded head impulse
      test (HIT) in comparison with standard caloric and rotational testing. To
      characterize the corresponding HIT catch-up saccade pattern to provide the basis
      for its salience to clinicians. METHODS: Horizontal HIT of graded acceleration
      (750 degrees-6,000 degrees/sec2) was measured with binocular dual search coils in
      14 patients with GVT and compared with 14 normal subjects and a control subject
      with total surgical BVL. RESULTS: Patients showed mostly symmetric HIT gain
      deficits with a continuous spectrum from almost normal to complete BVL. Gain
      deficits were present even at the lowest head accelerations. HIT gain correlated
      better with caloric (Spearman rho = 0.85, p = 0.0001) than rotational testing
      (rho = 0.55, p = 0.046). Cumulative amplitude of overt saccades after head
      impulses was 5.6 times larger in patients than in normal subjects. Compared with
      previously published patients after unilateral vestibular deafferentation, GVT
      patients with BVL generated only approximately half the percentage of covert
      saccades during head rotation (23% at 750 degrees/sec2 to 46% at 6,000
      degrees/sec2). CONCLUSIONS: Head impulse testing is useful for early bedside
      detection of gentamicin vestibulotoxicity because most patients, even those with
      partial bilateral vestibular loss (BVL), have large overt saccades. Covert
      saccades, which can conceal the extent of BVL, are only approximately half as
      frequent as in unilateral patients, but may be present even in total BVL.

PMID- 19380702
TI  - Pathologic correlates of diffusion MRI changes in Creutzfeldt-Jakob disease.
AB  - OBJECTIVE: The cause of hyperintense magnetic resonance changes and reduced
      apparent diffusion coefficient (ADC) in specific brain regions of patients with
      Creutzfeldt-Jakob disease (CJD) is unknown. Our aim was to determine the
      neuropathologic correlates of antemortem water ADC and normalized T2-weighted
      changes in patients with CJD. METHOD: Ten patients with CJD and 10 sex- and age
      matched healthy controls were studied by DWI and T2-weighted echoplanar MRI. At
      postmortem, patients with CJD were evaluated for semiquantitative assessment of
      gliosis and neuronal loss, spongiform changes, and abnormal PrP protein
      deposition in four cortical regions (occipital, parietal, and temporal cortex,
      and cingulate gyrus), thalamus, and striatum for a total of 60 regions of
      interest (ROI). RESULTS: Gliosis and neuronal loss correlated very highly with
      each other in the 60 ROIs. Where status spongiosus was absent, spongiform change
      correlated very highly with gliosis and neuronal loss in the cortex, but not in
      deep gray matter. Spongiform change was also significantly correlated with PrPSc
      load in both cortical and deep gray ROIs. In deep gray matter, ADC decreased with
      increasing spongiform change (R2 = 0.78; p < 0.001) and PrPSc load (R2 = 0.51; p
      = 0.003). In the cortex, ADC decreased with increases in all three, highly
      correlated, pathologic scores. CONCLUSION: Antemortem reductions in ADC values,
      typically found in patients with Creutzfeldt-Jakob disease (CJD), are correlated
      with spongiform changes seen at autopsy. This could be clearly established in the
      striatum and thalamus of our patients with CJD where the extent of spongiform
      change was not significantly correlated with gliosis or neuronal loss.

PMID- 19380703
TI  - Frequency of LGMD gene mutations in Italian patients with distinct clinical
      phenotypes.
AB  - BACKGROUND: The frequency of various limb-girdle muscular dystrophy (LGMD)
      molecular diagnoses has previously been investigated only in cohorts of patients
      presenting LGMD phenotype. METHODS: A total of 550 muscle biopsies underwent
      multiple protein screening (including calpain-3 functional assay) and extensive
      gene mutation analysis to examine the frequency of LGMD subtypes in patients with
      distinct clinical phenotypes (severe childhood-onset LGMD, adult-onset LGMD,
      distoproximal myopathy, and asymptomatic hyperCKemia). RESULTS: The percentage of
      molecularly ascertained cases directly relates with the degree of clinical
      involvement: 60% of total LGMD (77% of childhood-onset, 46% of adult-onset, 66%
      of distoproximal myopathy) and 14% of hyperCKemia. The higher number of molecular
      diagnoses in severe phenotypes might suggest that genes selected for our
      screening are those more frequently associated with severe LGMD, and that the
      hyperCKemia group includes heterogeneous diagnoses. The probability of obtaining
      a molecular diagnosis increases when a protein defect is found in a muscle
      biopsy: in such cases, we diagnosed 87% of LGMD and 76% of hyperCKemia.
      CONCLUSIONS: Diagnosing 77% of childhood-onset limb-girdle muscular dystrophy
      (LGMD) and 60% of total LGMD is an important result. The missing identification
      of gene mutations in about 40% of patients with typical LGMD phenotype suggests
      that unknown genetic or nongenetic etiologies are still to be recognized.
      Dysferlin, caveolin-3, and emerin protein defects invariably corresponded to
      primary disorders (100%), whereas a lower correlation was found for sarcoglycans
      (77%) and calpain-3 (84%). The different efficiency of genetic diagnosis after
      the identification of a protein defect in the various disorders is possibly due
      to different pathogenetic effects of mutations.

PMID- 19380704
TI  - Brain iron homeostasis and neurodegenerative disease.

PMID- 19380705
TI  - The D216H variant in the DYT1 gene: a susceptibility factor for dystonia in
      familial cases?

PMID- 19380706
TI  - Dystonic tremor presenting as parkinsonism: long-term follow-up of SWEDDs.

PMID- 19380707
TI  - A vaginal CSF leak.

PMID- 19380708
TI  - Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in
      Cholesterol Levels study.

PMID- 19380709
TI  - Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in
      Cholesterol Levels study.

PMID- 19380711
TI  - Heterogeneous expression of the adhesion receptor CD226 on murine NK and T cells
      and its function in NK-mediated killing of immature dendritic cells.
AB  - The adhesion receptor CD226 (DNAM-1) is a member of the Ig superfamily possessing
      two extracellular V-like domains. In humans, CD226 was shown to be expressed by
      NK as well as T cells. During T cell priming, CD226-mediated costimulatory
      signals may skew the subsequent differentiation into the Th1 pathway. In
      addition, CD226 expressed on NK and cytotoxic T cells is engaged by its counter
      receptor CD155, present on target cells, thereby triggering their elimination. We
      established mAb specifically recognizing mCD226, demonstrating that CD226 is
      expressed by precursor and mature but not developing T cells. In contrast, NK
      cells are distinguished by a rather heterogeneous CD226 expression profile. In
      addition, expression of CD226 appears coupled to that of other NK cell receptors,
      as high expression of CD226 was found to correlate with decreased proportions of
      Ly49D and H positive NK cells. Upon injection into mice, the anti-CD226
      antibodies caused selective depletion of CD8(+) T cells. Moreover, these
      antibodies as well as a naturally occurring CD226 splice variant lacking the
      outermost V-like domain were instrumental in determining that CD226 adheres to
      CD155 via its first domain. In addition, antibodies were identified as capable of
      blocking the CD226/CD155 interaction and to prevent NK-driven killing of immature
      DC. CD226 is thus the first mNK receptor identified to be essential for the
      elimination of this particular cell type.

PMID- 19380712
TI  - A new function of the Fas-FasL pathway in macrophage activation.
AB  - Upon infection with the protozoan parasite Leishmania major, susceptible BALB/c
      mice develop unhealing lesions associated with the maturation of CD4(+)Th2 cells
      secreting IL-4. In contrast, resistant C57BL/6 mice heal their lesions, because
      of expansion and secretion of IFN-gamma of CD4(+) Th1 cells. The Fas-FasL
      pathway, although not involved in Th cell differentiation, was reported to be
      necessary for complete resolution of lesions. We investigate here the role of IFN
      gamma and IL-4 on Fas-FasL nonapoptotic signaling events leading to the
      modulation of macrophage activation. We show that addition of FasL and IFN-gamma
      to BMMo led to their increased activation, as reflected by enhanced secretion of
      TNF, IL-6, NO, and the induction of their microbicidal activity, resulting in the
      killing of intracellular L. major. In contrast, the presence of IL-4 decreased
      the synergy of IFN-gamma/FasL significantly on macrophage activation and the
      killing of intracellular L. major. These results show that FasL synergizes with
      IFN-gamma to activate macrophages and that the tight regulation by IFN-gamma
      and/or IL-4 of the nonapoptotic signaling events triggered by the Fas-FasL
      pathway affects significantly the activation of macrophages to a microbicidal
      state and may thus contribute to the pathogenesis of L. major infection.

PMID- 19380710
TI  - Extinction circuits for fear and addiction overlap in prefrontal cortex.
AB  - Extinction is a form of inhibitory learning that suppresses a previously
      conditioned response. Both fear and drug seeking are conditioned responses that
      can lead to maladaptive behavior when expressed inappropriately, manifesting as
      anxiety disorders and addiction, respectively. Recent evidence indicates that the
      medial prefrontal cortex (mPFC) is critical for the extinction of both fear and
      drug-seeking behaviors. Moreover, a dorsal-ventral distinction is apparent within
      the mPFC, such that the prelimbic (PL-mPFC) cortex drives the expression of fear
      and drug seeking, whereas the infralimbic (IL-mPFC) cortex suppresses these
      behaviors after extinction. For conditioned fear, the dorsal-ventral dichotomy is
      accomplished via divergent projections to different subregions of the amygdala,
      whereas for drug seeking, it is accomplished via divergent projections to the
      subregions of the nucleus accumbens. Given that the mPFC represents a common node
      in the extinction circuit for these behaviors, treatments that target this region
      may help alleviate symptoms of both anxiety and addictive disorders by enhancing
      extinction memory.

PMID- 19380713
TI  - Enterohemorrhagic Escherichia coli raises the I-BAR.

PMID- 19380714
TI  - Ancient farming in eastern North America.

PMID- 19380715
TI  - The prehistory of compassion.

PMID- 19380716
TI  - Complex systems: from chemistry to systems biology.

PMID- 19380718
TI  - Sustainable water deliveries from the Colorado River in a changing climate.
AB  - The Colorado River supplies water to 27 million users in 7 states and 2 countries
      and irrigates over 3 million acres of farmland. Global climate models almost
      unanimously project that human-induced climate change will reduce runoff in this
      region by 10-30%. This work explores whether currently scheduled future water
      deliveries from the Colorado River system are sustainable under different climate
      change scenarios. If climate change reduces runoff by 10%, scheduled deliveries
      will be missed approximately 58% of the time by 2050. If runoff reduces 20%, they
      will be missed approximately 88% of the time. The mean shortfall when full
      deliveries cannot be met increases from approximately 0.5-0.7 billion cubic
      meters per year (bcm/yr) in 2025 to approximately 1.2-1.9 bcm/yr by 2050 out of a
      request of approximately 17.3 bcm/yr. Such values are small enough to be
      manageable. The chance of a year with deliveries <14.5 bcm/yr increases to 21% by
      midcentury if runoff reduces 20%, but such low deliveries could be largely
      avoided by reducing scheduled deliveries. These results are computed by using
      estimates of Colorado River flow from the 20th century, which was unusually wet;
      if the river reverts to its long-term mean, shortfalls increase another 1-1.5
      bcm/yr. With either climate-change or long-term mean flows, currently scheduled
      future water deliveries from the Colorado River are not sustainable. However, the
      ability of the system to mitigate droughts can be maintained if the various users
      of the river find a way to reduce average deliveries.

PMID- 19380717
TI  - IFN-gamma receptor signaling mediates spinal microglia activation driving
      neuropathic pain.
AB  - Neuropathic pain, a highly debilitating pain condition that commonly occurs after
      nerve damage, is a reflection of the aberrant excitability of dorsal horn
      neurons. This pathologically altered neurotransmission requires a communication
      with spinal microglia activated by nerve injury. However, how normal resting
      microglia become activated remains unknown. Here we show that in naive animals
      spinal microglia express a receptor for the cytokine IFN-gamma (IFN-gammaR) in a
      cell-type-specific manner and that stimulating this receptor converts microglia
      into activated cells and produces a long-lasting pain hypersensitivity evoked by
      innocuous stimuli (tactile allodynia, a hallmark symptom of neuropathic pain).
      Conversely, ablating IFN-gammaR severely impairs nerve injury-evoked microglia
      activation and tactile allodynia without affecting microglia in the contralateral
      dorsal horn or basal pain sensitivity. We also find that IFN-gamma-stimulated
      spinal microglia show up-regulation of Lyn tyrosine kinase and purinergic P2X(4)
      receptor, crucial events for neuropathic pain, and genetic approaches provide
      evidence linking these events to IFN-gammaR-dependent microglial and behavioral
      alterations. These results suggest that IFN-gammaR is a key element in the
      molecular machinery through which resting spinal microglia transform into an
      activated state that drives neuropathic pain.

PMID- 19380719
TI  - Histone deacetylases 1 and 2 control the progression of neural precursors to
      neurons during brain development.
AB  - The molecular mechanism by which neural progenitor cells commit to a specified
      lineage of the central nervous system remains unknown. We show that HDAC1 and
      HDAC2 redundantly control neuronal development and are required for neuronal
      specification. Mice lacking HDAC1 or HDAC2 in neuronal precursors show no overt
      histoarchitectural phenotypes, whereas deletion of both HDAC1 and HDAC2 in
      developing neurons results in severe hippocampal abnormalities, absence of
      cerebellar foliation, disorganization of cortical neurons, and lethality by
      postnatal day 7. These abnormalities in brain formation can be attributed to a
      failure of neuronal precursors to differentiate into mature neurons and to
      excessive cell death. These results reveal redundant and essential roles for
      HDAC1 and HDAC2 in the progression of neuronal precursors to mature neurons in
      vivo.

PMID- 19380720
TI  - Phytochromes promote seedling light responses by inhibiting four negatively
      acting phytochrome-interacting factors.
AB  - PIF3 is a phytochrome-interacting basic helix-loop-helix transcription factor
      that negatively regulates light responses, including hypocotyl elongation,
      cotyledon opening, and hypocotyl negative gravitropism. However, the role of PIF3
      in chlorophyll biosynthesis has not been clearly defined. Here, we show that PIF3
      also negatively regulates chlorophyll biosynthesis by repressing biosynthetic
      genes in the dark. Consistent with the gene expression patterns, the etiolated
      pif3 mutant accumulated a higher amount of protochlorophyllide and was bleached
      severely when transferred into light. The photobleaching phenotype of pif3 could
      be suppressed by the gun5 mutation and mimicked by overexpression of GUN5. When 4
      negative phytochrome-interacting protein genes (PIF1, PIF3, PIF4, and PIF5) were
      mutated, the resulting quadruple mutant seedlings displayed constitutive
      photomorphogenic phenotypes, including short hypocotyls, open cotyledons, and
      disrupted hypocotyl gravitropism in the dark. Microarray analysis further
      confirmed that the dark-grown quadruple mutant has a gene expression pattern
      similar to that of red light-grown WT. Together, our data indicate that 4
      phytochrome-interacting proteins are required for skotomorphogenesis and
      phytochromes activate photomorphogenesis by inhibiting these factors.

PMID- 19380721
TI  - Epistasis among HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci determines multiple
      sclerosis susceptibility.
AB  - Multiple sclerosis (MS), a common central nervous system inflammatory disease,
      has a major heritable component. Susceptibility is associated with the MHC class
      II region, especially HLA-DRB5*0101-HLA-DRB1*1501-HLA-DQA1*0102-HLA-DQB1*0602
      haplotypes(hereafter DR2), which dominate genetic contribution to MS risk. Marked
      linkage disequilibrium (LD) among these loci makes identification of a specific
      locus difficult. The once-leading candidate, HLA-DRB1*15, localizes to risk,
      neutral, and protective haplotypes. HLA-DRB1*15 and HLA-DQB1*0602, nearly always
      located together on a small ancestral chromosome segment, are strongly MS
      associated. One intervening allele on this haplotype, viz. HLA-DQA1*0102, shows
      no primary MS association. Two Canadian cohorts (n = 830 and n = 438 trios)
      genotyped for HLA-DRB1, HLA-DQA1 and HLA-DQB1 alleles were tested for association
      using TDT. To evaluate epistasis involving HLA-DRB1*15, transmissions from HLA
      DRB1*15-negative parents were stratified by the presence/absence of HLA-DRB1*15
      in affected offspring. All 3 alleles contribute to MS susceptibility through
      novel epistatic interactions. HLA-DQA1*0102 increased disease risk when combined
      with HLA-DRB1*1501 in trans, thereby unambiguously implicating HLA-DQ in MS
      susceptibility. Three-locus haplotypes demonstrated that HLA-DRB1*1501 and HLA
      DQB1*0602 each influence risk. Transmissions of rare morcellated DR2 haplotypes
      showed no interaction with HLA-DQA1*0102. Incomplete haplotypes bearing only HLA
      DRB1*1501 or HLA-DQB1*0602 did not predispose to MS. Balanced reciprocal
      transmission distortion can mask epistatic allelic association. These findings
      implicate epistasis among HLA class II alleles in human immune responses
      generally, provide partial explanation for intense linkage disequilibrium in the
      MHC, have relevance to animal models, and demonstrate key roles for DR2-specific
      interactions in MS susceptibility. MHC disease associations may be more generally
      haplotypic or diplotypic.

PMID- 19380722
TI  - Degenerate evolution of the hedgehog gene in a hemichordate lineage.
AB  - The discovery of a set of highly conserved genes implicated in patterning during
      animal development represents one of the most striking findings from the field of
      evolutionary developmental biology. Existence of these "developmental toolkit"
      genes in diverse taxa, however, does not necessarily imply that they always
      perform the same functions. Here, we demonstrate functional evolution in a major
      toolkit gene. hedgehog (hh) encodes a protein that undergoes autocatalytic
      cleavage, releasing a signaling molecule involved in major developmental
      processes, notably neural patterning. We find that the hh gene of a colonial
      pterobranch hemichordate, Rhabdopleura compacta, is expressed in a dramatically
      different pattern to its ortholog in a harrimaniid enteropneust hemichordate,
      Saccoglossus kowalevskii. These represent two of the three major hemichordate
      lineages, the third being the indirect developing ptychoderid enteropneusts. We
      also show that the normally well-conserved amino acid sequence of the
      autoproteolytic cleavage site has a derived change in S. kowalevskii. Using
      ectopic expression in Drosophila, we find that this amino acid substitution
      reduces the efficiency of Hh autocatalytic cleavage and its signaling function.
      We conclude that the Hh sequence and expression in S. kowalevskii represent the
      derived state for deuterostomes, and we argue that functional evolution
      accompanied secondary reduction of the central nervous system in harrimaniids.

PMID- 19380724
TI  - Epithelial sodium channel regulated by differential composition of a signaling
      complex.
AB  - Hormonal control of transepithelial sodium (Na(+)) transport utilizes
      phosphatidylinositide 3'-kinase (PI3K) and Raf-MAPK/ERK kinase (MEK)-ERK
      dependent signaling pathways, which impact numerous cell functions. How signals
      transmitted by these pathways are sorted and appropriately transmitted to alter
      Na(+) transport without altering other physiologic processes is not well
      understood. Here, we report the identification of a signaling complex that
      selectively modulates the cell surface expression of the epithelial sodium
      channel (ENaC), an ion channel that is essential for fluid and electrolyte
      balance in mammals. Raf-1 and the ubiquitin ligase, Nedd4-2, are constitutively
      expressed inhibitory components of this ENaC regulatory complex, which interact
      with, and decrease the expression of, cell surface ENaC. The activities of Nedd4
      2 and Raf-1 are inhibited cooperatively by the PI3K-dependent kinase serum- and
      glucocorticoid-induced kinase 1 (SGK1), and the Raf-1-interacting protein
      glucocorticoid-induced leucine zipper (GILZ1), which are aldosterone-stimulated
      components of the complex. Together, SGK1 and GILZ1 synergistically stimulate
      ENaC cell surface expression. Interestingly, GILZ1 and SGK1 do not have
      synergistic, and in fact have opposite, effects on an unrelated activity, FKHRL1
      driven gene transcription. Together, these data suggest that GILZ1 and SGK1
      provide a physical and functional link between the PI3K- and Raf-1-dependent
      signaling modules and represent a unique mechanism for specifically controlling
      Na(+) transport without inappropriately activating other cell functions.

PMID- 19380723
TI  - Insights into pilus assembly and secretion from the structure and functional
      characterization of usher PapC.
AB  - Ushers constitute a family of bacterial outer membrane proteins responsible for
      the assembly and secretion of surface organelles such as the pilus. The structure
      at 3.15-A resolution of the usher pyelonephritis-associated pili C (PapC)
      translocation domain reveals a 24-stranded kidney-shaped beta-barrel, occluded by
      an internal plug domain. The dimension of the pore allows tandem passage of
      individual folded pilus subunits in an upright pilus growth orientation, but is
      insufficient for accommodating donor strand exchange. The molecular packing
      revealed by the crystal structure shows that 2 PapC molecules in head-to-head
      orientation interact via exposed beta-strand edges, which could be the preferred
      dimer interaction in solution. In vitro reconstitution of fiber assemblies
      suggest that PapC monomers may be sufficient for fiber assembly and secretion;
      both the plug domain and the C-terminal domain of PapC are required for filament
      assembly, whereas the N-terminal domain is mainly responsible for recruiting the
      chaperone-subunit complexes to the usher. The plug domain has a dual function:
      gating the beta-pore and participating in pilus assembly.

PMID- 19380725
TI  - Role of a distal pocket in the catalytic O2 reduction by cytochrome c oxidase
      models immobilized on interdigitated array electrodes.
AB  - Five iron porphyrins with different superstructures were immobilized on self
      assembled-monolayer (SAM)-coated interdigitated-array (IDAs) gold-platinum
      electrodes. The selectivity of the catalysts i.e., limited formation of partially
      reduced oxygen species (PROS) in the electrocatalytic reduction of dioxygen, is a
      function of 2 rates: (i) the rate of electron transfer from the electrode to the
      catalyst, which is controlled by the length, and conjugation of the linker from
      the catalyst to the electrode and (ii) the rate of bound oxygen (superoxide)
      hydrolysis, which correlates with the presence of a water cluster in the gas
      binding pocket influencing the rate of oxygen binding; these factors are
      controlled by the nature of the porphyrin superstructure. The structurally
      biomimetic Tris-imidazole model is the most selective.

PMID- 19380726
TI  - EphrinB2 coordinates the formation of a morphological boundary and cell
      epithelialization during somite segmentation.
AB  - During early morphogenesis, tissue segregation is often accompanied by changes in
      cell shape. To understand how such coordination is regulated, somitogenesis was
      used as a model. When a somite forms in the anterior end of the presomitic
      mesoderm, an intersomitic boundary (gap) emerges, and it is rapidly followed by
      cell epithelialization at this border. It has been known that the gap formation
      is regulated by intercellular signals. We here demonstrate that cMeso-1, the
      chicken homolog of mouse Mesp2, up-regulates EphA4 in the cells located
      posteriorly to a forming boundary. This in turn activates EphrinB2-reverse
      signals in the anteriorly juxtaposed cells, where the EphrinB2 signal is
      sufficient to cause a gap formation and cell epithelialization cell-autonomously.
      During these processes, Cdc42 needs to be repressed via tyrosine phosphorylation
      of EphrinB2. This is the first demonstration that Ephrin-reverse signal acts as a
      platform that couples distinct morphogenetic changes in cell polarity and tissue
      shape.

PMID- 19380727
TI  - Minimal molecular constraints for respiratory droplet transmission of an avian
      human H9N2 influenza A virus.
AB  - Pandemic influenza requires interspecies transmission of an influenza virus with
      a novel hemagglutinin (HA) subtytpe that can adapt to its new host through either
      reassortment or point mutations and transmit by aerosolized respiratory droplets.
      Two previous pandemics of 1957 and 1968 resulted from the reassortment of low
      pathogenic avian viruses and human subtypes of that period; however, conditions
      leading to a pandemic virus are still poorly understood. Given the endemic
      situation of avian H9N2 influenza with human-like receptor specificity in Eurasia
      and its occasional transmission to humans and pigs, we wanted to determine
      whether an avian-human H9N2 reassortant could gain respiratory transmission in a
      mammalian animal model, the ferret. Here we show that following adaptation in the
      ferret, a reassortant virus carrying the surface proteins of an avian H9N2 in a
      human H3N2 backbone can transmit efficiently via respiratory droplets, creating a
      clinical infection similar to human influenza infections. Minimal changes at the
      protein level were found in this virus capable of respiratory droplet
      transmission. A reassortant virus expressing only the HA and neuraminidase (NA)
      of the ferret-adapted virus was able to account for the transmissibility,
      suggesting that currently circulating avian H9N2 viruses require little
      adaptation in mammals following acquisition of all human virus internal genes
      through reassortment. Hemagglutinin inhibition (HI) analysis showed changes in
      the antigenic profile of the virus, which carries profound implications for
      vaccine seed stock preparation against avian H9N2 influenza. This report
      illustrates that aerosolized respiratory transmission is not exclusive to current
      human H1, H2, and H3 influenza subtypes.

PMID- 19380728
TI  - Neandertal birth canal shape and the evolution of human childbirth.
AB  - Childbirth is complicated in humans relative to other primates. Unlike the
      situation in great apes, human neonates are about the same size as the birth
      canal, making passage difficult. The birth mechanism (the series of rotations
      that the neonate must undergo to successfully negotiate its mother's birth canal)
      distinguishes humans not only from great apes, but also from lesser apes and
      monkeys. Tracing the evolution of human childbirth is difficult, because the
      pelvic skeleton, which forms the margins of the birth canal, tends to survive
      poorly in the fossil record. Only 3 female individuals preserve fairly complete
      birth canals, and they all date to earlier phases of human evolution. Here we
      present a virtual reconstruction of a female Neandertal pelvis from Tabun,
      Israel. The size of Tabun's reconstructed birth canal indicates that childbirth
      was about as difficult in Neandertals as in present-day humans, but the canal's
      shape indicates that Neandertals had a more primitive birth mechanism. A
      significant shift in childbirth apparently occurred quite late in human
      evolution, during the last few hundred thousand years. Such a late shift
      underscores the uniqueness of human childbirth and the divergent evolutionary
      trajectories of Neandertals and the lineage leading to present-day humans.

PMID- 19380730
TI  - Spatial and seasonal patterns in climate change, temperatures, and precipitation
      across the United States.
AB  - Changes in climate during the 20th century differ from region to region across
      the United States. We provide strong evidence that spatial variations in US
      temperature trends are linked to the hydrologic cycle, and we also present unique
      information on the seasonal and latitudinal structure of the linkage. We show
      that there is a statistically significant inverse relationship between trends in
      daily temperature and average daily precipitation across regions. This linkage is
      most pronounced in the southern United States (30-40 degrees N) during the May
      June time period and, to a lesser extent, in the northern United States (40-50
      degrees N) during the July-August time period. It is strongest in trends in
      maximum temperatures (T(max)) and 90th percentile exceedance trends (90PET), and
      less pronounced in the T(max) 10PET and the corresponding T(min) statistics, and
      it is robust to changes in analysis period. Although previous studies suggest
      that areas of increased precipitation may have reduced trends in temperature
      compared with drier regions, a change in sign from positive to negative trends
      suggests some additional cause. We show that trends in precipitation may account
      for some, but not likely all, of the cause point to evidence that shows that
      dynamical patterns (El Nino/Southern Oscillation, North Atlantic Oscillation,
      etc.) cannot account for the observed effects during May-June. We speculate that
      changing aerosols, perhaps related to vegetation changes, and increased strength
      of the aerosol direct and indirect effect may play a role in the observed
      linkages between these indices of temperature change and the hydrologic cycle.

PMID- 19380729
TI  - Phycomyces MADB interacts with MADA to form the primary photoreceptor complex for
      fungal phototropism.
AB  - The fungus Phycomyces blakesleeanus reacts to environmental signals, including
      light, gravity, touch, and the presence of nearby objects, by changing the speed
      and direction of growth of its fruiting body (sporangiophore). Phototropism,
      growth toward light, shares many features in fungi and plants but the molecular
      mechanisms remain to be fully elucidated. Phycomyces mutants with altered
      phototropism were isolated approximately 40 years ago and found to have mutations
      in the mad genes. All of the responses to light in Phycomyces require the
      products of the madA and madB genes. We showed that madA encodes a protein
      similar to the Neurospora blue-light photoreceptor, zinc-finger protein WC-1. We
      show here that madB encodes a protein similar to the Neurospora zinc-finger
      protein WC-2. MADA and MADB interact to form a complex in yeast 2-hybrid assays
      and when coexpressed in E. coli, providing evidence that phototropism and other
      responses to light are mediated by a photoresponsive transcription factor
      complex. The Phycomyces genome contains 3 genes similar to wc-1, and 4 genes
      similar to wc-2, many of which are regulated by light in a madA or madB dependent
      manner. We did not detect any interactions between additional WC proteins in
      yeast 2-hybrid assays, which suggest that MADA and MADB form the major
      photoreceptor complex in Phycomyces. However, the presence of multiple wc genes
      in Phycomyces may enable perception across a broad range of light intensities,
      and may provide specialized photoreceptors for distinct photoresponses.

PMID- 19380731
TI  - The most influential journals: Impact Factor and Eigenfactor.

PMID- 19380732
TI  - Feedback inactivation of D-serine synthesis by NMDA receptor-elicited
      translocation of serine racemase to the membrane.
AB  - D-serine is a physiological coagonist of N-methyl D-aspartate receptors (NMDARs)
      that plays a major role in several NMDAR-dependent events. In this study we
      investigate mechanisms regulating D-serine production by the enzyme serine
      racemase (SR). We now report that NMDAR activation promotes translocation of SR
      to the plasma membrane, which dramatically reduces the enzyme activity. Membrane
      bound SR isolated from rat brain is not extracted from the membrane by high
      detergent and salt concentration, indicating a strong association. Colocalization
      studies indicate that most membrane-bound SR is located at the plasma membrane
      and dendrites, with much less SR observed in other types of membrane. NMDAR
      activation promotes translocation of the cytosolic SR to the membrane, resulting
      in reduced D-serine synthesis, and this effect is averted by blockade of NMDARs.
      In primary neuronal cultures, SR translocation to the membrane is blocked by a
      palmitoylation inhibitor, indicating that membrane binding is mediated by fatty
      acid acylation of SR. In agreement, we found that SR is acylated in transfected
      neuroblastoma cells using [(3)H]palmitate or [(3)H]octanoic acid as precursors.
      In contrast to classical S-palmitoylation of cysteines, acylation of SR occurs
      through the formation of an oxyester bond with serine or threonine residues. In
      addition, we show that phosphorylation of Thr-227 is also required for steady
      state binding of SR to the membrane under basal, nonstimulated condition. We
      propose that the inhibition of D-serine synthesis caused by translocation of SR
      to the membrane provides a fail-safe mechanism to prevent NMDAR overactivation in
      vicinal cells or synapses.

PMID- 19380733
TI  - Retraction for Litovchick and Szostak. "Selection of cyclic peptide aptamers to
      HCV IRES RNA using mRNA display".

PMID- 19380735
TI  - Mangroves protected villages and reduced death toll during Indian super cyclone.
AB  - Protection against coastal disasters has been identified as an important service
      of mangrove ecosystems. Empirical studies on this service have been criticized,
      however, for using small samples and inadequately controlling for confounding
      factors. We used data on several hundred villages to test the impact of mangroves
      on human deaths during a 1999 super cyclone that struck Orissa, India. We found
      that villages with wider mangroves between them and the coast experienced
      significantly fewer deaths than ones with narrower or no mangroves. This finding
      was robust to the inclusion of a wide range of other variables to our statistical
      model, including controls for the historical extent of mangroves. Although
      mangroves evidently saved fewer lives than an early warning issued by the
      government, the retention of remaining mangroves in Orissa is economically
      justified even without considering the many benefits they provide to human
      society besides storm-protection services.

PMID- 19380734
TI  - Specific glycosphingolipids mediate epithelial-to-mesenchymal transition of human
      and mouse epithelial cell lines.
AB  - Epithelial-to-mesenchymal cell transition (EMT) is a basic process in embryonic
      development and cancer progression. The present study demonstrates involvement of
      glycosphingolipids (GSLs) in the EMT process by using normal murine mammary gland
      NMuMG, human normal bladder HCV29, and human mammary carcinoma MCF7 cells.
      Treatment of these cells with D-threo-1-(3',4'-ethylenedioxy)phenyl-2
      palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4), the glucosylceramide (GlcCer)
      synthase inhibitor, which depletes all GSLs derived from GlcCer, (i) down
      regulated expression of a major epithelial cell marker, E-cadherin; (ii) up
      regulated expression of mesenchymal cell markers vimentin, fibronectin, and N
      cadherin; (iii) enhanced haptotactic cell motility; and (iv) converted epithelial
      to fibroblastic morphology. These changes also were induced in these cell lines
      with TGF-beta, which is a well-documented EMT inducer. A close association
      between specific GSL changes and EMT processes induced by EtDO-P4 or TGF-beta is
      indicated by the following findings: (i) The enhanced cell motility of EtDO-P4
      treated cells was abrogated by exogenous addition of GM2 or Gg4, but not GM1 or
      GM3, in all 3 cell lines. (ii) TGF-beta treatment caused changes in the GSL
      composition of cells. Notably, Gg4 or GM2 was depleted or reduced in NMuMG, and
      GM2 was reduced in HCV29. (iii) Exogenous addition of Gg4 inhibited TGF-beta
      induced changes of morphology, motility, and levels of epithelial and mesenchymal
      markers. These observations indicate that specific GSLs play key roles in
      defining phenotypes associated with EMT and its reverse process (i.e.,
      mesenchymal-to-epithelial transition).

PMID- 19380736
TI  - PIF3 is a repressor of chloroplast development.
AB  - The phytochrome-interacting factor PIF3 has been proposed to act as a positive
      regulator of chloroplast development. Here, we show that the pif3 mutant has a
      phenotype that is similar to the pif1 mutant, lacking the repressor of
      chloroplast development PIF1, and that a pif1pif3 double mutant has an additive
      phenotype in all respects. The pif mutants showed elevated protochlorophyllide
      levels in the dark, and etioplasts of pif mutants contained smaller prolamellar
      bodies and more prothylakoid membranes than corresponding wild-type seedlings,
      similar to previous reports of constitutive photomorphogenic mutants. Consistent
      with this observation, pif1, pif3, and pif1pif3 showed reduced hypocotyl
      elongation and increased cotyledon opening in the dark. Transfer of 4-d-old dark
      grown seedlings to white light resulted in more chlorophyll synthesis in pif
      mutants over the first 2 h, and analysis of gene expression in dark-grown pif
      mutants indicated that key tetrapyrrole regulatory genes such as HEMA1 encoding
      the rate-limiting step in tetrapyrrole synthesis were already elevated 2 d after
      germination. Circadian regulation of HEMA1 in the dark also showed reduced
      amplitude and a shorter, variable period in the pif mutants, whereas expression
      of the core clock components TOC1, CCA1, and LHY was largely unaffected.
      Expression of both PIF1 and PIF3 was circadian regulated in dark-grown seedlings.
      PIF1 and PIF3 are proposed to be negative regulators that function to integrate
      light and circadian control in the regulation of chloroplast development.

PMID- 19380737
TI  - Coordinated regulation by Shp2 tyrosine phosphatase of signaling events
      controlling insulin biosynthesis in pancreatic beta-cells.
AB  - Intracellular signaling by which pancreatic beta-cells synthesize and secrete
      insulin in control of glucose homeostasis is not fully understood. Here we show
      that Shp2, a cytoplasmic tyrosine phosphatase possessing 2 SH2 domains,
      coordinates signaling events required for insulin biosynthesis in beta-cells.
      Mice with conditional ablation of the Shp2/Ptpn11 gene in the pancreas exhibited
      defective glucose-stimulated insulin secretion and impaired glucose tolerance.
      Consistently, siRNA-mediated Shp2-knockdown in rat insulinoma INS-1 832/13 cells
      resulted in decreased insulin production and secretion despite an increase in
      cellular ATP. Shp2 modulates the strength of signals flowing through Akt/FoxO1
      and Erk pathways, culminating in control of Pdx1 expression and activity on Ins1
      and Ins2 promoters, and forced Pdx1 expression rescued insulin production in Shp2
      knockdown beta-cells. Therefore, Shp2 acts as a signal coordinator in beta-cells,
      orchestrating multiple pathways controlling insulin biosynthesis to maintain
      glucose homeostasis.

PMID- 19380738
TI  - Simplified and effective motor control based on muscle synergies to exploit
      musculoskeletal dynamics.
AB  - The basic hypothesis of producing a range of behaviors using a small set of motor
      commands has been proposed in various forms to explain motor behaviors ranging
      from basic reflexes to complex voluntary movements. Yet many fundamental
      questions regarding this long-standing hypothesis remain unanswered. Indeed,
      given the prominent nonlinearities and high dimensionality inherent in the
      control of biological limbs, the basic feasibility of a low-dimensional
      controller and an underlying principle for its creation has remained elusive. We
      propose a principle for the design of such a controller, that it endeavors to
      control the natural dynamics of the limb, taking into account the nature of the
      task being performed. Using this principle, we obtained a low-dimensional model
      of the hindlimb and a set of muscle synergies to command it. We demonstrate that
      this set of synergies was capable of producing effective control, establishing
      the viability of this muscle synergy hypothesis. Finally, by combining the low
      dimensional model and the muscle synergies we were able to build a relatively
      simple controller whose overall performance was close to that of the system's
      full-dimensional nonlinear controller. Taken together, the results of this study
      establish that a low-dimensional controller is capable of simplifying control
      without degrading performance.

PMID- 19380739
TI  - Spatial ensemble statistics are efficient codes that can be represented with
      reduced attention.
AB  - There is a great deal of structural regularity in the natural environment, and
      such regularities confer an opportunity to form compressed, efficient
      representations. Although this concept has been extensively studied within the
      domain of low-level sensory coding, there has been limited focus on efficient
      coding in the field of visual attention. Here we show that spatial patterns of
      orientation information ("spatial ensemble statistics") can be efficiently
      encoded under conditions of reduced attention. In our task, observers monitored
      for changes to the spatial pattern of background elements while they were
      attentively tracking moving objects in the foreground. By using stimuli that
      enable us to dissociate changes in local structure from changes in the ensemble
      structure, we found that observers were more sensitive to changes to the
      background that altered the ensemble structure than to changes that did not alter
      the ensemble structure. We propose that reducing attention to the background
      increases the amount of noise in local feature representations, but that spatial
      ensemble statistics capitalize on structural regularities to overcome this noise
      by pooling across local measurements, gaining precision in the representation of
      the ensemble.

PMID- 19380740
TI  - Political complexity predicts the spread of ethnolinguistic groups.
AB  - Human languages show a remarkable degree of variation in the area they cover.
      However, the factors governing the distribution of human cultural groups such as
      languages are not well understood. While previous studies have examined the role
      of a number of environmental variables the importance of cultural factors has not
      been systematically addressed. Here we use a geographical information system
      (GIS) to integrate information about languages with environmental, ecological,
      and ethnographic data to test a number of hypotheses that have been proposed to
      explain the global distribution of languages. We show that the degree of
      political complexity and type of subsistence strategy exhibited by societies are
      important predictors of the area covered by a language. Political complexity is
      also strongly associated with the latitudinal gradient in language area, whereas
      subsistence strategy is not. We argue that a process of cultural group selection
      favoring more complex societies may have been important in shaping the present
      day global distribution of language diversity.

PMID- 19380741
TI  - Single-nucleotide discrimination in immobilized DNA oligonucleotides with a
      biological nanopore.
AB  - The sequencing of individual DNA strands with nanopores is under investigation as
      a rapid, low-cost platform in which bases are identified in order as the DNA
      strand is transported through a pore under an electrical potential. Although the
      preparation of solid-state nanopores is improving, biological nanopores, such as
      alpha-hemolysin (alphaHL), are advantageous because they can be precisely
      manipulated by genetic modification. Here, we show that the transmembrane beta
      barrel of an engineered alphaHL pore contains 3 recognition sites that can be
      used to identify all 4 DNA bases in an immobilized single-stranded DNA molecule,
      whether they are located in an otherwise homopolymeric DNA strand or in a
      heteropolymeric strand. The additional steps required to enable nanopore DNA
      sequencing are outlined.

PMID- 19380742
TI  - A continuum of genetic divergence from sympatric host races to species in the pea
      aphid complex.
AB  - Sympatric populations of insects adapted to different host plants, i.e., host
      races, are good models to investigate how natural selection can promote
      speciation in the face of ongoing gene flow. However, host races are documented
      in very few model systems and their gradual evolution into good species, as
      assumed under a Darwinian view of species formation, lacks strong empirical
      support. We aim at resolving this uncertainty by investigating host
      specialization and gene flow among populations of the pea aphid complex,
      Acyrthosiphon pisum. Genetic markers and tests of host plant specificity indicate
      the existence of at least 11 well-distinguished sympatric populations associated
      with different host plants in Western Europe. Population assignment tests show
      variable migration and hybridization rates among sympatric populations,
      delineating 8 host races and 3 possible species. Notably, hybridization
      correlates negatively with genetic differentiation, forming a continuum of
      population divergence toward virtually complete speciation. The pea aphid complex
      thus illustrates how ecological divergence can be sustained among many
      hybridizing populations and how insect host races blend into species by gradual
      reduction of gene flow.

PMID- 19380744
TI  - Depletion of interfering antibodies in chronic hepatitis C patients and
      vaccinated chimpanzees reveals broad cross-genotype neutralizing activity.
AB  - Using human immune globulins made from antihepatitis C virus (HCV)-positive
      plasma, we recently identified two antibody epitopes in the E2 protein at
      residues 412-426 (epitope I) and 434-446 (epitope II). Whereas epitope I is
      highly conserved among genotypes, epitope II varies. We discovered that epitope I
      was implicated in HCV neutralization whereas the binding of non-neutralizing
      antibody to epitope II disrupted virus neutralization mediated by antibody
      binding at epitope I. These findings suggested that, if this interfering
      mechanism operates in vivo during HCV infection, a neutralizing antibody against
      epitope I can be restrained by an interfering antibody, which may account for the
      persistence of HCV even in the presence of an abundance of neutralizing
      antibodies. We tested this hypothesis by affinity depletion and peptide-blocking
      of epitope-II-specific antibodies in plasma of a chronically HCV-infected patient
      and recombinant E1E2 vaccinated chimpanzees. We demonstrate that, by removing the
      restraints imposed by the interfering antibodies to epitope-II, neutralizing
      activity can be revealed in plasma that previously failed to neutralize viral
      stock in cell culture. Further, cross-genotype neutralization could be generated
      from monospecific plasma. Our studies contribute to understanding the mechanisms
      of antibody-mediated neutralization and interference and provide a practical
      approach to the development of more potent and broadly reactive hepatitis C
      immune globulins.

PMID- 19380743
TI  - Charting the molecular network of the drug target Bcr-Abl.
AB  - The tyrosine kinase Bcr-Abl causes chronic myeloid leukemia and is the cognate
      target of tyrosine kinase inhibitors like imatinib. We have charted the protein
      protein interaction network of Bcr-Abl by a 2-pronged approach. Using a
      monoclonal antibody we have first purified endogenous Bcr-Abl protein complexes
      from the CML K562 cell line and characterized the set of most tightly-associated
      interactors by MS. Nine interactors were subsequently subjected to tandem
      affinity purifications/MS analysis to obtain a molecular interaction network of
      some hundred cellular proteins. The resulting network revealed a high degree of
      interconnection of 7 "core" components around Bcr-Abl (Grb2, Shc1, Crk-I, c-Cbl,
      p85, Sts-1, and SHIP-2), and their links to different signaling pathways.
      Quantitative proteomics analysis showed that tyrosine kinase inhibitors lead to a
      disruption of this network. Certain components still appear to interact with Bcr
      Abl in a phosphotyrosine-independent manner. We propose that Bcr-Abl and other
      drug targets, rather than being considered as single polypeptides, can be
      considered as complex protein assemblies that remodel upon drug action.

PMID- 19380745
TI  - Transcriptome transfer produces a predictable cellular phenotype.
AB  - Cellular phenotype is the conglomerate of multiple cellular processes involving
      gene and protein expression that result in the elaboration of a cell's particular
      morphology and function. It has been thought that differentiated postmitotic
      cells have their genomes hard wired, with little ability for phenotypic
      plasticity. Here we show that transfer of the transcriptome from differentiated
      rat astrocytes into a nondividing differentiated rat neuron resulted in the
      conversion of the neuron into a functional astrocyte-like cell in a time
      dependent manner. This single-cell study permits high resolution of molecular and
      functional components that underlie phenotype identity. The RNA population from
      astrocytes contains RNAs in the appropriate relative abundances that give rise to
      regulatory RNAs and translated proteins that enable astrocyte identity. When
      transferred into the postmitotic neuron, the astrocyte RNA population converts
      44% of the neuronal host cells into the destination astrocyte-like phenotype. In
      support of this observation, quantitative measures of cellular morphology, single
      cell PCR, single-cell microarray, and single-cell functional analyses have been
      performed. The host-cell phenotypic changes develop over many weeks and are
      persistent. We call this process of RNA-induced phenotype changes, transcriptome
      induced phenotype remodeling.

PMID- 19380746
TI  - Phonon softening and crystallographic orientation of strained graphene studied by
      Raman spectroscopy.
AB  - We present a systematic study of the Raman spectra of optical phonons in graphene
      monolayers under tunable uniaxial tensile stress. Both the G and 2D bands exhibit
      significant red shifts. The G band splits into 2 distinct subbands (G(+), G(-))
      because of the strain-induced symmetry breaking. Raman scattering from the G(+)
      and G(-) bands shows a distinctive polarization dependence that reflects the
      angle between the axis of the stress and the underlying graphene crystal axes.
      Polarized Raman spectroscopy therefore constitutes a purely optical method for
      the determination of the crystallographic orientation of graphene.

PMID- 19380747
TI  - Rapid sensitive analysis of cysteine rich peptide venom components.
AB  - Disulfide-rich peptide venoms from animals such as snakes, spiders, scorpions,
      and certain marine snails represent one of nature's great diversity libraries of
      bioactive molecules. The various species of marine cone shells have alone been
      estimated to produce >50,000 distinct peptide venoms. These peptides have
      stimulated considerable interest because of their ability to potently alter the
      function of specific ion channels. To date, only a small fraction of this immense
      resource has been characterized because of the difficulty in elucidating their
      primary structures, which range in size between 10 and 80 aa, include up to 5
      disulfide bonds, and can contain extensive posttranslational modifications. The
      extraordinary complexity of crude venoms and the lack of DNA databases for many
      of the organisms of interest present major analytical challenges. Here, we
      describe a strategy that uses mass spectrometry for the elucidation of the mature
      peptide toxin components of crude venom samples. Key to this strategy is our use
      of electron transfer dissociation (ETD), a mass spectrometric fragmentation
      technique that can produce sequence information across the entire peptide
      backbone. However, because ETD only yields comprehensive sequence coverage when
      the charge state of the precursor peptide ion is sufficiently high and the m/z
      ratio is low, we combined ETD with a targeted chemical derivatization strategy to
      increase the charge state of cysteine-containing peptide toxins. Using this
      strategy, we obtained full sequences for 31 peptide toxins, using just 7% of the
      crude venom from the venom gland of a single cone snail (Conus textile).

PMID- 19380748
TI  - A gain in GABAA receptor synaptic strength in thalamus reduces oscillatory
      activity and absence seizures.
AB  - Neural inhibition within the thalamus is integral in shaping thalamocortical
      oscillatory activity. Fast, synaptic inhibition is primarily mediated by
      activation of heteropentameric GABA(A) receptor complexes. Here, we examined the
      synaptic physiology and network properties of mice lacking GABA(A) receptor
      alpha3, a subunit that in thalamus is uniquely expressed by inhibitory neurons of
      the reticular nucleus (nRT). Deletion of this subunit produced a powerful
      compensatory gain in inhibitory postsynaptic response in nRT neurons. Although,
      other forms of inhibitory and excitatory synaptic transmission in the circuit
      were unchanged, evoked thalamic oscillations were strongly dampened in alpha3
      knockout mice. Furthermore, pharmacologically induced thalamocortical absence
      seizures displayed a reduction in length and power in alpha3 knockout mice. These
      studies highlight the role of GABAergic inhibitory strength within nRT in the
      maintenance of thalamic oscillations, and demonstrate that inhibitory intra-nRT
      synapses are a critical control point for regulating higher order thalamocortical
      network activity.

PMID- 19380749
TI  - Retraction for Ma et al. "Glucose regulates the effects of leptin on hypothalamic
      POMC neurons".

PMID- 19380750
TI  - Flexible neural mechanisms of cognitive control within human prefrontal cortex.
AB  - A major challenge in research on executive control is to reveal its functional
      decomposition into underlying neural mechanisms. A typical assumption is that
      this decomposition occurs solely through anatomically based dissociations. Here
      we tested an alternative hypothesis that different cognitive control processes
      may be implemented within the same brain regions, with fractionation and
      dissociation occurring on the basis of temporal dynamics. Regions within lateral
      prefrontal cortex (PFC) were examined that, in a prior study, exhibited
      contrasting temporal dynamics between older and younger adults during performance
      of the AX-CPT cognitive control task. The temporal dynamics in younger adults fit
      a proactive control pattern (primarily cue-based activation), whereas in older
      adults a reactive control pattern was found (primarily probe-based activation).
      In the current study, we found that following a period of task-strategy training,
      these older adults exhibited a proactive shift within a subset of the PFC
      regions, normalizing their activity dynamics toward young adult patterns.
      Conversely, under conditions of penalty-based monetary incentives, the younger
      adults exhibited a reactive shift some of the same regions, altering their
      temporal dynamics toward the older adult baseline pattern. These experimentally
      induced crossover patterns of temporal dynamics provide strong support for dual
      modes of cognitive control that can be flexibly shifted within PFC regions, via
      modulation of neural responses to changing task conditions or behavioral goals.

PMID- 19380751
TI  - Complexity in bacterial cell-cell communication: quorum signal integration and
      subpopulation signaling in the Bacillus subtilis phosphorelay.
AB  - A common form of quorum sensing in gram-positive bacteria is mediated by peptides
      that act as phosphatase regulators (Phr) of receptor aspartyl phosphatases
      (Raps). In Bacillus subtilis, several Phr signals are integrated in sporulation
      phosphorelay signal transduction. We theoretically demonstrate that the
      phosphorelay can act as a computational machine performing a sensitive division
      operation of kinase-encoded signals by quorum-modulated Rap signals, indicative
      of cells computing a "food per cell" estimate to decide whether to enter
      sporulation. We predict expression from the rapA-phrA operon to bifurcate as
      relative environmental signals change in a developing population. We
      experimentally observe that the rapA-phrA operon is heterogeneously induced in
      sporulating microcolonies. Uninduced cells sporulate rather synchronously early
      on, whereas the RapA/PhrA subpopulation sporulates less synchronously throughout
      later stationary phase. Moreover, we show that cells sustain PhrA expression
      during periods of active growth. Together with the model, these findings suggest
      that the phosphorelay may normalize environmental signals by the size of the
      (sub)population actively competing for nutrients (as signaled by PhrA).
      Generalizing this concept, the various Phrs could facilitate subpopulation
      communication in dense isogenic communities to control the physiological
      strategies followed by differentiated subpopulations by interpreting
      (environmental) signals based on the spatiotemporal community structure.

PMID- 19380752
TI  - Nutrition intervention: a strategy against systemic inflammatory syndrome.
AB  - BACKGROUND: Sepsis and septic shock syndrome are the leading causes of death in
      critically ill patients. Lipopolysaccharide (LPS) released by the colonic
      microorganisms may translocate across a compromised lumen, leading to upregulated
      reactive oxidative stress, inflammation, and sepsis. The authors examined an
      enteral formula high in cysteine (antioxidant precursor), omega-3 fatty acids,
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and prebiotic
      fructooligosaccharides (FOS) against systemic inflammatory syndrome. METHODS:
      Rats were allocated to (1) standard soy-based diet high in cysteine and crude
      fiber and devoid of EPA-DHA (CHOW); (2) whey-peptide-based liquid diet high in
      cysteine, EPA-DHA, and FOS (CYSPUFA); or (3) casein-based liquid isonitrogenous
      diet, low in cysteine and devoid of EPA-DHA-FOS (CASN). Liquid diets provided 25%
      and CHOW, 23% of calories as protein. After 6 days on diets, rats received an
      intraperitoneal injection of LPS or saline. Animals gained weight on their
      respective diets and lost weight after LPS administration. The CYSPUFA group lost
      considerably less weight (vs CASN or CHOW, P < .05). Inflammatory cytokines
      significantly increased by 4 hours and subsided 18 hours after assault. The CASN
      group showed elevated liver enzyme alanine aminotransferase release from damaged
      hepatocytes and developed severe hepatic pathology with low hematocrit. The CHOW
      group developed more severe hepatic lesions compared with those on liquid diets.
      Concentration of liver enzyme and pathology were improved in rats receiving
      CYSPUFA. CONCLUSIONS: Data indicate that CYSPUFA, a diet rich in EPA-DHA-FOS,
      protects against LPS-induced systemic inflammatory responses and warrants
      clinical studies in critically ill patients.

PMID- 19380754
TI  - Comment on "Dendritic cells and monocyte/macrophages that create the IL-6/APRIL
      rich lymph node microenvironment where plasmablasts mature".

PMID- 19380753
TI  - Rationale and design of the pediatric critical illness stress-induced immune
      suppression (CRISIS) prevention trial.
AB  - Despite implementation of CDC recommendations and bundled interventions for
      preventing catheter-associated blood stream infection, ventilator-associated
      pneumonia, or urinary catheter-associated infections, nosocomial infections and
      sepsis remain a significant cause of morbidity and mortality in critically ill
      children. Recent studies suggest that acquired critical illness stress-induced
      immune suppression (CRISIS) plays a role in the development of nosocomial
      infection and sepsis. This condition can be related to inadequate zinc, selenium,
      and glutamine levels, as well as hypoprolactinemia, leading to stress-induced
      lymphopenia, a predominant T(H)2 monocyte/macrophage state, and subsequent immune
      suppression. Prolonged immune dysfunction increases the likelihood of nosocomial
      infections associated with invasive devices. Although strategies to prevent
      common complications of critical illness are routinely employed (eg, prophylaxis
      for gastrointestinal bleeding, thrombophlebitis), no prophylactic strategy is
      used to prevent stress-induced immune suppression. This is the authors' rationale
      for the pediatric CRISIS prevention trial (NCT00395161), designed as a
      randomized, double-blind, controlled clinical investigation to determine if daily
      enteral supplementation with zinc, selenium, and glutamine as well as parenteral
      metoclopramide (a dopamine 2 receptor antagonist that reverses hypoprolactinemia)
      prolongs the time until onset of nosocomial infection or sepsis in critically ill
      children compared to enteral supplementation with whey protein. If effective,
      this combined nutritional and pharmacologic approach may lessen the excess
      morbidity and mortality as well as resource utilization associated with
      nosocomial infections and sepsis in this population. The authors present the
      design and analytic plan for the CRISIS prevention trial.

PMID- 19380755
TI  - Comment on "Engineering antibody heavy chain CDR3 to create a phage display Fab
      library rich in antibodies that bind charged carbohydrates".

PMID- 19380757
TI  - Identification of the last cog in a ligand-independent signaling machine?

PMID- 19380758
TI  - Analysis and expression of a cloned pre-T cell receptor gene. Science. 1994. 266:
      1208-1212.

PMID- 19380759
TI  - World Malaria Day 2009: what malaria knows about the immune system that
      immunologists still do not.
AB  - Malaria kills >1 million children each year, and there is little doubt that an
      effective vaccine would play a central role in preventing these deaths. However,
      the strategies that proved so successful in developing the vaccines we have today
      may simply not be adequate to confront complex, persistent infectious diseases,
      including malaria, AIDS, and tuberculosis. We believe that the development of a
      highly effective vaccine will require a better understanding of several features
      of the immune response to malaria. At the top of the list is the complex and
      ancient relationship between the parasite that causes malaria and the immune
      system that enables the parasite to persist in an otherwise functional immune
      system. A close second is the antigenic targets in malaria and how to overcome
      the enormous polymorphism of these targets. Meeting these challenges represents a
      call to arms of basic immunologists to advance our knowledge of malaria immunity.

PMID- 19380760
TI  - Cutting edge: phosphatidylinositol 4,5-bisphosphate concentration at the APC side
      of the immunological synapse is required for effector T cell function.
AB  - Little is known about the signaling that occurs in an APC during contact with a T
      cell. In this article we report the concentration of the signaling lipid
      phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) at the APC side of the
      immunological synapse. In both human and mouse cells, a PI(4,5)P(2)-specific
      fluorescent reporter, PH-GFP (where PH is pleckstrin homology), detected an Ag
      dependent enrichment of PI(4,5)P(2) at the synapse between Ag-specific T cells
      and APC. When PIP(4,5)P(2) was sequestered by a high concentration of PH-GFP
      reporter, cells were less susceptible to CTL-mediated lysis than control cells.
      These findings suggest a new regulatory target for modulating immune function
      that may be exploited for immune escape by pathogens and tumors.

PMID- 19380761
TI  - Cutting edge: rescue of pre-TCR but not mature TCR signaling in mice expressing
      membrane-targeted SLP-76.
AB  - SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa)
      organizes signaling from immunoreceptors, including the platelet collagen
      receptor, the pre-TCR, and the TCR, and is required for T cell development. In
      this study we examine a mouse in which wild-type SLP-76 is replaced with a mutant
      constitutively targeted to the cell membrane. Membrane-targeted SLP-76 (MTS)
      supports ITAM signaling in platelets and from the pre-TCR. Signaling from the
      mature TCR, however, is defective in MTS thymocytes, resulting in failed T cell
      differentiation. Defective thymic selection by MTS is not rescued by a SLP-76
      mutant whose localization is restricted to the cytosol. Thus, fixed localization
      of SLP-76 reveals differential requirements for the subcellular localization of
      signaling complexes downstream of the pre-TCR vs mature TCR.

PMID- 19380762
TI  - Cutting edge: regulatory T cells do not require stimulation through their TCR to
      suppress.
AB  - The mechanism and stimulatory requirements of regulatory T cell (Treg)-mediated
      suppression are still unclear. To assess the requirement for Treg stimulation by
      cognate peptide:MHC, we used T cells from OTII and AND TCR transgenic mice that
      are specific for and restricted by distinct, noncrossreactive peptide:MHC
      combinations. This allowed us to independently activate Tregs and their
      conventional T cell (Tconv) targets. Surprisingly, we found that suppression can
      occur in the absence of peptide:MHC-mediated stimulation of Tregs. This
      suppression was Treg dependent and not due to cold target inhibition. Using Rag1(
      /-) TCR transgenic T cells, we show that regulation of Tconv proliferation by
      heterogeneous Tregs is not due to alloreactivity or crossreactivity. Finally,
      using anti-TCR-Vbeta8-coated microbeads and Vbeta8(-) Tregs, we show that TCR
      stimulation-independent suppression can occur in the absence of APCs. These data
      suggest that Tregs may possess constitutive regulatory activity that can be
      mediated in the absence of cognate peptide:MHC-TCR stimulation.

PMID- 19380763
TI  - Cutting edge: genetic characterization of IFN-producing killer dendritic cells.
AB  - The combined phenotypic expression of CD11c(low)B220(+)CD122(+)DX5(+) has been
      used to define a novel cell type termed IFN-producing killer dendritic cells
      (IKDC). IKDC readily produce IFN-gamma and demonstrate spontaneous cytotoxic
      activity toward tumors, suggesting that a modulation of IKDC number may be
      beneficial in cancer treatment. We examined various mouse strains and found that
      IKDC number was highly variable between the different strains. A linkage analysis
      associated the distal arm of chromosome 7 with variations in IKDC number. The
      genetic contribution of chromosome 7 to the regulation of IKDC number was
      confirmed through the use of congenic mice. We further demonstrate that IKDC
      proportion is regulated by intrinsic hematopoietic factors. We discuss the role
      of various candidate genes in the regulation of this newly described cell type
      and its implication in therapy.

PMID- 19380764
TI  - Cutting edge: shift in antigen dependence by an antiviral MHC class Ib-restricted
      CD8 T cell response during persistent viral infection.
AB  - The requirement for Ag in maintaining memory CD8 T cells often differs between
      infections that are acutely resolved and those that persist. Using the mouse
      polyoma virus (PyV) persistent infection model, we recently described a novel CD8
      T cell response directed to a PyV peptide presented by Q9, an MHC class Ib
      molecule. This antiviral Q9-restricted CD8 T cell response is characterized by a
      3-mo expansion phase followed by a long-term plateau phase. In this study, we
      demonstrate that viral Ag is required for this protracted inflation phase but is
      dispensable for the maintenance of this Q9-restricted CD8 T cell response.
      Moreover, proliferation by memory T cells, not recruitment of naive PyV-specific
      T cells, is primarily responsible for Q9-restricted, anti-PyV CD8 T cell
      inflation. These data reveal a dynamic shift in Ag dependence by an MHC class Ib
      restricted memory CD8 T cell response during a persistent viral infection.

PMID- 19380765
TI  - CD59 blockade enhances antigen-specific CD4+ T cell responses in humans: a new
      target for cancer immunotherapy?
AB  - CD59, a broadly expressed GPI-anchored molecule, regulates formation of the
      membrane attack complex of the complement cascade. We previously demonstrated
      that mouse CD59 also down-modulates CD4(+) T cell activity in vivo. In this
      study, we explored the role of CD59 on human CD4(+) T cells. Our data demonstrate
      that CD59 is up-regulated on activated CD4(+) T cells and serves to down-modulate
      their activity in response to polyclonal and Ag-specific stimulation. The
      therapeutic potential of this finding was explored using T cells isolated from
      colorectal cancer patients. The findings were striking and indicated that
      blockade of CD59 significantly enhanced the CD4(+) T cell response to two
      different tumor Ags. These data highlight the potential for manipulating CD59
      expression on T cells for boosting weak immune responses, such as those found in
      individuals with cancer.

PMID- 19380766
TI  - Ig-like transcript 3 regulates expression of proinflammatory cytokines and
      migration of activated T cells.
AB  - Ig-like transcript 3 (ILT3), an inhibitory receptor expressed by APC is involved
      in functional shaping of T cell responses toward a tolerant state. We have
      previously demonstrated that membrane (m) and soluble (s) ILT3 induce allogeneic
      tolerance to human islet cells in humanized NOD/SCID mice. Recombinant sILT3
      induces the differentiation of CD8(+) T suppressor cells both in vivo and in
      vitro. To better understand the molecular mechanisms by which ILT3 suppresses
      immune responses, we have generated ILT3 knockdown (ILT3KD) dendritic cells (DC)
      and analyzed the phenotypic and functional characteristics of these cells. In
      this study, we report that silencing of ILT3 expression in DC (ILT3KD DC)
      increases TLR responsiveness to their specific ligands as reflected in increased
      synthesis and secretion of proinflammatory cytokines such as IL-1alpha, IL-1beta,
      and IL-6 and type I IFN. ILT3KD-DC also secretes more CXCL10 and CXCL11
      chemokines in response to TLR ligation, thus accelerating T cell migration in
      diffusion chamber experiments. ILT3KD-DC elicit increased T cell proliferation
      and synthesis of proinflammatory cytokines IFN-gamma and IL-17A both in MLC and
      in culture with autologous DC pulsed with CMV protein. ILT3 signaling results in
      inhibition of NF-kappaB and, to a lesser extent, MAPK p38 pathways in DC. Our
      results suggest that ILT3 plays a critical role in the control of inflammation.

PMID- 19380767
TI  - Locally administered TLR7 agonists drive systemic antitumor immune responses that
      are enhanced by anti-CD40 immunotherapy.
AB  - Topical application of tumors with the TLR7 agonist imiquimod is an effective
      adjunct treatment for a range of primary dermatological cancers. However, for
      therapy to be effective against a broad range of solid tumor types, it must
      promote a strong systemic antitumor response that targets metastases in addition
      to primary tumor. We therefore investigated the potential of locally delivered
      imiquimod to stimulate an effective systemic antitumor response in a murine model
      of malignant mesothelioma (AB1-HA) with primary and distal tumors (dual tumor).
      Persistent delivery of imiquimod into primary tumor significantly retarded tumor
      growth in all treated mice compared with vehicle control. This local antitumor
      immune response required both CD8 T cells and NK cells, but not CD4 T cells, and
      was reliant on type I IFN induction. In vivo CTL studies and Ly6A/E staining of
      lymphocytes suggested that local imiquimod treatment had indeed induced a
      systemic, Ag-specific CD8 response. However, notably this response was not
      sufficient to retard the growth of an untreated distal tumor. Because local
      imiquimod treatment did not induce significant CD4 T cell responses, we
      investigated the efficacy of combining imiquimod with agonistic CD40 Ab (as a
      surrogate for CD4 T cell help). Combination of locally delivered imiquimod with
      systemic anti-CD40 immunotherapy not only significantly enhanced the local
      antitumor response, with 30% complete resolution, but it was also effective at
      significantly retarding growth of distal tumor. These results demonstrate that
      antitumor responses induced by locally delivered TLR7 agonists can be harnessed
      systemically for treating distal tumor.

PMID- 19380768
TI  - PI3K p110beta positively regulates lipopolysaccharide-induced IL-12 production in
      human macrophages and dendritic cells and JNK1 plays a novel role.
AB  - The PI3K family is thought to participate in TLR signaling, and it has been
      reported to be a negative regulator of TLR-mediated production of IL-12, a key
      inducer of Th1 responses. However, the role of individual PI3K subtypes in IL-12
      production remains obscure. We defined the distinct regulation of LPS-mediated IL
      12 production by p110alpha and p110beta catalytic subunits of PI3K in human APCs.
      We observed that knockdown of PI3K p110beta by small interfering RNA (siRNA)
      suppressed both LPS-induced IL-12 protein production and mRNA expression in
      monocyte-derived macrophages and dendritic cells (DCs). Knockdown of PI3K
      p110alpha by siRNA reduced LPS-induced IL-12 protein production in both cell
      types. Conversely, knockdown of PI3K p110alpha suppressed LPS-induced IL-12 mRNA
      expression in monocyte-derived macrophages but minimally affected monocyte
      derived DCs. PI3K p110beta siRNA inhibited JNK activation, but not p38 MAPK or
      ERK activation, stimulated by LPS, while PI3K p110alpha siRNA did not affect LPS
      induced JNK, p38 MAPK, or ERK activation in both cell types. Transfection of
      siRNA against JNK1, JNK2, and both decreased LPS-induced IL-12 production.
      Furthermore, PI3K p110beta siRNA attenuated LPS-induced JNK1 phosphorylation,
      while not affecting JNK2 phosphorylation. Our findings indicate that PI3K
      p110beta positively controls LPS-induced IL-12 production through the JNK1
      dependent pathway in human macrophages and DCs.

PMID- 19380769
TI  - The role of TCR specificity and clonal competition during reconstruction of the
      peripheral T cell pool.
AB  - Survival of peripheral CD8(+) T cells requires TCR interactions with peptide-MHC
      complexes (p-MHC). In the adult mouse, in the presence of homeostatic mechanisms
      that strictly control T cell numbers, it is likely that diverse T cell clones may
      compete for shared patterns of p-MHC. In the present study, we investigate
      whether the recognition of p-MHC overlaps between different T cell populations
      and what role does this process plays in the establishment of the peripheral T
      cell pools. Using an experimental strategy that follows the fate of adoptively
      transferred polyclonal T cells into RAG(0/0) or different TCR transgenic RAG(0/0)
      hosts, we demonstrate that T cells bearing different TCR specificities share
      identical TCR-specific requirements for survival and lymphopenia driven
      proliferation (LDP). This interclonal competition applies to both naive and
      activated/memory T cells and is partially determined by the clone size of the
      established/resident T cells. However, clonal competition with activated/memory
      resident T cells impacts differently on the fate of newly produced bone-marrow
      derived T cells or adoptively transferred peripheral T cells. Overall, our
      findings indicate that p-MHC define multiple diverse resource niches that can be
      shared by T cells from different compartments.

PMID- 19380770
TI  - PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma
      patients.
AB  - The programmed death 1 (PD-1) receptor is a negative regulator of activated T
      cells and is up-regulated on exhausted virus-specific CD8(+) T cells in
      chronically infected mice and humans. Programmed death ligand 1 (PD-L1) is
      expressed by multiple tumors, and its interaction with PD-1 resulted in tumor
      escape in experimental models. To investigate the role of PD-1 in impairing
      spontaneous tumor Ag-specific CD8(+) T cells in melanoma patients, we have
      examined the effect of PD-1 expression on ex vivo detectable CD8(+) T cells
      specific to the tumor Ag NY-ESO-1. In contrast to EBV, influenza, or Melan-A/MART
      1-specific CD8(+) T cells, NY-ESO-1-specific CD8(+) T cells up-regulated PD-1
      expression. PD-1 up-regulation on spontaneous NY-ESO-1-specific CD8(+) T cells
      occurs along with T cell activation and is not directly associated with an
      inability to produce cytokines. Importantly, blockade of the PD-1/PD-L1 pathway
      in combination with prolonged Ag stimulation with PD-L1(+) APCs or melanoma cells
      augmented the number of cytokine-producing, proliferating, and total NY-ESO-1
      specific CD8(+) T cells. Collectively, our findings support the role of PD-1 as a
      regulator of NY-ESO-1-specific CD8(+) T cell expansion in the context of chronic
      Ag stimulation. They further support the use of PD-1/PD-L1 pathway blockade in
      cancer patients to partially restore NY-ESO-1-specific CD8(+) T cell numbers and
      functions, increasing the likelihood of tumor regression.

PMID- 19380771
TI  - TRBP homolog interacts with eukaryotic initiation factor 6 (eIF6) in
      Fenneropenaeus chinensis.
AB  - The HIV transactivating response RNA-binding protein (TRBP) plays an important
      role in many biological processes. We have cloned three cDNAs from newly
      identified genes in the TRBP family from Fenneropenaeus chinensis. These genes
      have been designated Fc-TRBP1-3. Recombinant Fc-TRBP1, which was produced in
      Escherichia coli, was used for panning of a T7 phage display library of the
      Chinese shrimp hemocytes. From this panning, Fc-eukaryotic initiation factor 6
      (Fc-eIF6) was isolated and sequenced. Fc-eIF6 was then cloned, recombinantly
      expressed, and shown to interact with Fc-TRBP by the performance of pull-down
      assays and Far Western blot analysis. Expression of Fc-TRBP was detected in many
      tissues, with elevated expression in the heart, gill, and intestine in the early
      stages of infection by the white spot syndrome virus (WSSV), and enhanced
      expression in most tissues following challenge with Vibrio anguillarum. Western
      blot studies confirmed the increased expression of Fc-TRBP in the gill after WSSV
      infection. The expression pattern of eIF6 was also analyzed and its expression
      was also up-regulated in intestine of WSSV-challenged shrimp. The replication of
      WSSV was reduced after injection of Fc-TRBP. These results indicate that Fc-TRBP
      and Fc-eIF6 may be components of the RNA-induced silencing complex (RISC), and
      thereby play a crucial role in the antiviral defense response of shrimp.

PMID- 19380772
TI  - Regulation of NK cell function by human granulocyte arginase.
AB  - The arginine-hydrolyzing enzyme arginase is constitutively expressed by human
      polymorphonuclear granulocytes (PMN). Upon PMN cell death arginase is liberated
      and depletes arginine in the microenvironment. This amino acid depletion
      suppresses T cell proliferation and cytokine secretion and emerges as a key
      mechanism of immunosuppression during chronic inflammation and tumor growth. Here
      we show that PMN arginase also severely impairs key functions of primary human NK
      cells as well as IL-2-activated NK cells. In the absence of arginine, NK cell
      proliferation and IL-12/IL-18-induced secretion of IFN-gamma are severely
      diminished. In contrast, NK cell viability, granule exocytosis, and cytotoxicity
      are independent of extracellular arginine. The mechanism of NK cell suppression
      by arginine depletion is posttranscriptional since mRNA transcript frequency is
      unaffected upon NK cell activation in the absence of arginine. Finally, we
      demonstrate that human purulent exudate ex vivo inhibits NK cell functions
      exclusively due to liberated arginase. Arginase inhibitors are therefore
      promising pharmacological agents to treat unwanted suppression of the innate (NK
      cell) as well as the adaptive (T cell) immune system.

PMID- 19380773
TI  - Autoantigen immunization at different sites reveals a role for anti-inflammatory
      effects of IFN-gamma in regulating susceptibility to experimental autoimmune
      encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis is induced in B10.PL (H-2(u)) mice by
      immunization with the immunodominant N-terminal epitope of myelin basic protein,
      Ac1-9. In the present study, we show that the site of immunization impacts
      disease incidence and severity. This effect is more marked in female mice than in
      males. Although immunization in the flanks is effective in eliciting disease,
      delivery of Ag in the footpad and tailbase results in poor induction. Analyses of
      the immune responses in female mice following different immunization regimens
      indicates that resistance to disease is accompanied by higher levels of IFN-gamma
      and CD11b(+)Gr-1(int) myeloid cells. Such myeloid cells are known to have a
      suppressive function, and consistent with this knowledge, blockade of IFN-gamma
      results in increased disease activity and decreased levels of splenic CD11b(+)Gr
      1(int) cells. Conversely, injection of adjuvants (CFA or Pam(3)CSK(4)) in the
      footpad decreases experimental autoimmune encephalomyelitis incidence and
      severity. Our study indicates that the site of immunization can impact the
      magnitude of the ensuing inflammatory response, and that at a certain threshold a
      protective, regulatory circuit can be elicited.

PMID- 19380774
TI  - Liver X receptors control IgE expression in B cells.
AB  - B lymphocytes play a fundamental role in the development of IgE-dependent
      allergic immune reactions. Upon appropriate activation, IgE class switch
      recombination is initiated in B cells, followed by terminal differentiation to
      IgE-secreting plasmablasts. This process is controlled by different nuclear
      receptors, including receptors for vitamin D, retinoids, and peroxisome
      proliferator-activated receptor-gamma ligands. In this study, we show
      constitutive expression of the nuclear liver X receptor (LXR)alpha and LXRbeta in
      peripheral human B cells. Activation of LXRs reduced secreted IgE (-68% +/- 11)
      in CD40 and IL-4 activated B cells. The production of other isotypes, including
      IgG, IgM, IgA and B cell homeostatic parameters were not significantly altered by
      LXR activation. We identified inhibitory action of LXR activation on IgE
      production involving reduced phosphorylation of JNK and increased membrane CD23
      expression (38% +/- 11). The biological significance of our findings was
      validated by showing that systemic treatment of type I-sensitized BALB/c mice
      with LXR ligands reduced the serum concentrations of Ag-specific IgE in a dose
      dependent manner (maximum, -52% +/- 14). Thus, our data indicates that LXRs are
      involved in the control of IgE secretion by differentiating B cells.

PMID- 19380775
TI  - Galectin-1 tunes TCR binding and signal transduction to regulate CD8 burst size.
AB  - T cell burst size is regulated by the duration of TCR engagement and balanced
      control of Ag-induced activation, expansion, and apoptosis. We found that
      galectin-1-deficient CD8 T cells undergo greater cell division in response to TCR
      stimulation, with fewer dividing cells undergoing apoptosis. TCR-induced ERK
      signaling was sustained in activated galectin-1-deficient CD8 T cells and
      antagonized by recombinant galectin-1, indicating galectin-1 modulates TCR feed
      forward/feedback loops involved in signal discrimination and procession.
      Furthermore, recombinant galectin-1 antagonized binding of agonist tetramers to
      the TCR on activated OT-1 T cells. Finally, galectin-1 produced by activated Ag
      specific CD8 T cells negatively regulated burst size and TCR avidity in vivo.
      Therefore, galectin-1, inducibly expressed by activated CD8 T cells, functions as
      an autocrine negative regulator of peripheral CD8 T cell TCR binding, signal
      transduction, and burst size. Together with recent findings demonstrating that
      gal-1 promotes binding of agonist tetramers to the TCR of OT-1 thymocytes, these
      studies identify galectin-1 as a tuner of TCR binding, signaling, and functional
      fate determination that can differentially specify outcome, depending on the
      developmental and activation stage of the T cell.

PMID- 19380776
TI  - IL-23 drives pathogenic IL-17-producing CD8+ T cells.
AB  - IL-17-producing CD8(+) T cells (Tc17) appear to play a role in a range of
      conditions, such as autoimmunity and cancer. Thus far, Tc17 cells have been only
      marginally studied, resulting in a paucity of data on their biology and function.
      We demonstrate that Tc17 and Th17 cells share similar developmental
      characteristics, including the previously unknown promoting effect of IL-21 on
      Tc17 cell differentiation and IL-23-dependent expression of IL-22. Both STAT1 and
      STAT4 are required for optimal development of Tc17 cells and maximal secretion of
      cytokines. Tc17 cells are cytotoxic, and they can be either pathogenic or
      nonpathogenic upon adoptive transfer in the model of autoimmune diabetes. Tc17
      cells treated with TGF-beta1 plus IL-6 are not diabetogenic, whereas IL-23
      treated cells potently induce the disease. IL-17A and IL-17F are necessary but
      not sufficient for diabetes induction by Tc17 cells. Tc17 cells treated with TGF
      beta1 plus IL-6 or IL-23 likely differ in pathogenicity due to their disparate
      capacity to attract other immune cells and initiate inflammation.

PMID- 19380777
TI  - Id3 restricts the developmental potential of gamma delta lineage during
      thymopoiesis.
AB  - Most T cell progenitors develop into the alphabeta T cell lineage with the
      exception of a small fraction contributing to the gammadelta lineage throughout
      postnatal life. T cell progenitors usually commit to the alphabeta lineage upon
      the expression of a fully rearranged and functional TCRbeta gene, and most cells
      that fail to produce a functional TCRbeta-chain will die instead of adopting the
      alternative gammadelta T cell fate. What prevents these cells from continuing
      TCRgamma rearrangement and adopting the gammadelta T cell fate is not known. In
      this study, we show that functional loss of Id3 results in a significant increase
      of gammadelta T cell production from progenitor cells undergoing TCRbeta
      rearrangement. The enhanced gammadelta T cell development correlated with
      increased TCRgamma gene rearrangement involving primarily Vgamma1.1 in Id3
      deficient mice. We further show that Id3 deficiency promotes gammadelta T cell
      production in a manner independent of TCRbeta-chain expression. Our data
      indicates that Id3 suppresses Vgamma1.1 rearrangement and gammadelta lineage
      potential among T cell progenitors that have completed TCRbeta gene rearrangement
      without producing a functional TCRbeta protein.

PMID- 19380778
TI  - A functional IL-13 receptor is expressed on polarized murine CD4+ Th17 cells and
      IL-13 signaling attenuates Th17 cytokine production.
AB  - IL-17A is produced from Th17 cells, and is involved in many autoimmune and
      inflammatory diseases. IL-13R has not previously been reported to be functionally
      expressed on T cells; however, we found that purified BALB/c CD4(+) cells
      polarized to Th17 with TGF-beta, IL-6, and IL-23 have increased mRNA and protein
      expression of IL-13R alpha1 and mRNA expression of IL-4R alpha compared with Th0,
      Th1, or Th2 polarized cells. The addition of IL-13 at Th17 polarization
      negatively regulated IL-17A and IL-21 expression, and reduced the number of
      CD4(+) T cells producing IL-17A. Further, adding IL-13 at the time of Th17 cell
      restimulation attenuated IL-17A expression. CD4(+) Th17 polarized cells from IL-4
      knockout (KO) mice also had IL-13-induced inhibition of IL-17A production, but
      this was not observed in IL-4R KO and STAT6 KO mice. Addition of IL-13 at
      polarization increased IL-13R expression in wild-type Th17 cells. Further, IL-13
      administration during Th17 polarization down-regulated retinoic acid-related
      gammaT, the transcription required for Th17 development; increased STAT6
      phosphorylation, and up-regulated GATA3, the transcription factor activated
      during the development of Th2 cells. This IL-13-mediated effect was specific to
      Th17 cells as IL-13 neither decreased IFN-gamma expression by Th1 cells nor
      affected Th2 cell production of IL-4. Collectively, we have shown that Th17 cells
      express a functional IL-13R and that IL-13 negatively regulates IL-17A and IL-21
      production by decreasing retinoic acid-related-gammaT expression and while
      increasing phosphorylation of STAT6 and GATA3 expression. Therefore, therapeutic
      intervention inhibiting IL-13 production could have adverse consequences by up
      regulating Th17 inflammation in certain disease states.

PMID- 19380780
TI  - Experimental autoimmune encephalomyelitis in Lewis rats: IFN-beta acts as a
      tolerogenic adjuvant for induction of neuroantigen-dependent tolerance.
AB  - Cytokine-Ag fusion proteins represent a novel approach for induction of Ag
      specific tolerance and may constitute an efficient therapy for autoimmune
      disease. This study addressed whether a fusion protein containing rat IFN-beta
      and the encephalitogenic 73-87 determinant of myelin basic protein (i.e., the
      neuroantigen, or NAg) could prevent or treat experimental autoimmune
      encephalomyelitis (EAE) in Lewis rats. The optimal structure of the fusion
      protein was comprised of the rat IFN-beta cytokine as the N-terminal domain with
      an enterokinase (EK) linker to the NAg domain. Both cytokine and NAg domains had
      full biological activity. Subcutaneous administration of 1 nmol of IFNbeta-NAg
      fusion protein in saline on days -21, -14, and -7 before encephalitogenic
      challenge on day 0 resulted in a substantial attenuation of EAE. In contrast,
      administration of IFN-beta or NAg alone did not affect susceptibility to EAE. The
      covalent attachment of IFN-beta and NAg was not necessary, because separate
      injections of IFN-beta and NAg at adjacent sites were as effective as injection
      of IFNbeta-NAg for prevention of disease. When treatment was initiated after
      disease onset, the rank order of inhibitory activity was as follows: the IFNbeta
      NAg fusion protein > or = a mixture of IFN-beta plus NAg > IFN-beta > NAg. The
      novel finding that IFN-beta acts as a tolerogenic adjuvant as well as a
      tolerogenic fusion partner may have significance for development of tolerogenic
      vaccines.

PMID- 19380779
TI  - Lipopolysaccharide potentiates effector T cell accumulation into nonlymphoid
      tissues through TRIF.
AB  - LPS is a natural adjuvant that potentiates Ag-specific T cell survival and Th1
      differentiation by stimulating MyD88 and Toll/IL-1R domain-containing adaptor
      inducing IFN-beta (TRIF) signaling pathways. In this study, we reveal the TRIF
      pathway is critical for amplifying murine effector T cell accumulation into
      nonlymphoid tissues following immunization with Ag plus LPS. Although LPS
      increased the accumulation of splenic T cells in TRIF-deficient mice, markedly
      fewer T cells were recovered from liver and lung in comparison to wild type. Most
      of the T cells primed in TRIF-deficient mice failed to up-regulate CXCR3 and had
      an overall reduced capacity to produce IFN-gamma, demonstrating effector T cell
      differentiation was linked to their migration. To investigate the role of TRIF
      dependent cytokines, neutralization studies were performed in wild type mice.
      Although TNF neutralization reduced T cell numbers, its coneutralization with IL
      10 unexpectedly restored the T cells, suggesting the balance between pro- and
      anti-inflammatory cytokines influences T cell survival rather than their
      magnitude. To investigate a role for costimulatory molecules, we tested whether
      the T cell defect in TRIF-deficient mice could be corrected with enforced
      costimulation. Boosting with a CD40 agonist in addition to LPS restored the
      effector CD8 T cell response in livers of TRIF-deficient mice while only
      partially restoring CD4 T cells, suggesting that LPS primes CD8 and CD4 T cell
      immunity through different mechanisms. Overall, our data support targeting TRIF
      for vaccines aimed to direct immune responses to nonlymphoid tissues.

PMID- 19380781
TI  - Surface CD152 (CTLA-4) expression and signaling dictates longevity of CD28null T
      cells.
AB  - CD28(null) T cells are a highly enriched subset of proinflammatory T cells in
      patients with autoimmune diseases that are oligoclonal and autoreactive. In this
      study, we analyzed the role of CD152 signaling on the longevity of human
      CD28(null) T cells. Using a sensitive staining method for CD152, we show that
      human CD4(+)CD28(null) and CD8(+)CD28(null) T cells rapidly express surface
      CD152. Serological inactivation of CD152 using specific Fab or blockade of CD152
      ligands using CTLA-4Ig in CD4(+)CD28(null) and CD8(+)CD28(null) T cells enhances
      apoptosis in a Fas/FasL-dependent manner. CD152 cross-linking on activated
      CD28(null) cells prevents activation-induced cell death as a result of reduced
      caspase activity. Apoptosis protection conferred by CD152 is mediated by
      phosphatidylinositol 3'-kinase-dependent activation of the kinase Akt, resulting
      in enhanced phosphorylation and thereby inhibition of the proapoptotic molecule
      Bad. We show that signals triggered by CD152 act directly on activated CD28(null)
      T lymphocytes and, due to its exclusive expression as a receptor for CD80/CD86 on
      CD28(null) T cells, prevention of CD152-mediated signaling is likely a target
      mechanism taking place during therapy with CTLA-4Ig. Our data imply strongly that
      antagonistic approaches using CD152 signals for chronic immune responses might be
      beneficial.

PMID- 19380782
TI  - Protective CD8 T cell memory is impaired during chronic CD70-driven
      costimulation.
AB  - Chronic infection results in continuous formation and exhaustion of effector CD8
      T cells and in failure of memory CD8 T cell development. Expression of CD70 and
      other molecules that provide costimulation to T cells is maintained during
      chronic infection. To analyze the impact of constitutive CD70-driven
      costimulation, we generated transgenic mice expressing CD70 specifically on T
      cells. We show that CD70 promoted accumulation of CD8 T cells with
      characteristics strikingly similar to exhausted effector CD8 T cells found during
      chronic infection. CD70 on T cells provided costimulation that enhanced primary
      CD8 T cell responses against influenza. In contrast, memory CD8 T cell
      maintenance and protection against secondary challenge with influenza was
      impaired. Interestingly, we found no effect on the formation of either effector
      or memory CD4 T cells. We conclude that constitutive expression of CD70 is
      sufficient to deregulate the CD8 T cell differentiation pathway of acute
      infection reminiscent of events in chronic infection.

PMID- 19380784
TI  - ATLa, an aspirin-triggered lipoxin A4 synthetic analog, prevents the inflammatory
      and fibrotic effects of bleomycin-induced pulmonary fibrosis.
AB  - Despite an increase in the knowledge of mechanisms and mediators involved in
      pulmonary fibrosis, there are no successful therapeutics available. Lipoxins (LX)
      and their 15-epimers, aspirin-triggered LX (ATL), are endogenously produced
      eicosanoids with potent anti-inflammatory and proresolution effects. To date, few
      studies have been performed regarding their effect on pulmonary fibrosis. In the
      present study, using C57BL/6 mice, we report that bleomycin (BLM)-induced lung
      fibrosis was prevented by the concomitant treatment with an ATL synthetic analog,
      ATLa, which reduced inflammation and matrix deposition. ATLa inhibited BLM
      induced leukocyte accumulation and alveolar collapse as evaluated by histology
      and morphometrical analysis. Moreover, Sirius red staining and lung
      hydroxyproline content showed an increased collagen deposition in mice receiving
      BLM alone that was decreased upon treatment with the analog. These effects
      resulted in benefits to pulmonary mechanics, as ATLa brought to normal levels
      both lung resistance and compliance. Furthermore, the analog improved mouse
      survival, suggesting an important role for the LX pathway in the control of
      disease establishment and progression. One possible mechanism by which ATLa
      restrained fibrosis was suggested by the finding that BLM-induced myofibroblast
      accumulation/differentiation in the lung parenchyma was also reduced by both
      simultaneous and posttreatment with the analog (alpha-actin
      immunohistochemistry). Interestingly, ATLa posttreatment (4 days after BLM)
      showed similar inhibitory effects on inflammation and matrix deposition, besides
      the TGF-beta level reduction in the lung, reinforcing an antifibrotic effect. In
      conclusion, our findings show that LX and ATL can be considered as promising
      therapeutic approaches to lung fibrotic diseases.

PMID- 19380783
TI  - Pathogenic natural antibodies recognizing annexin IV are required to develop
      intestinal ischemia-reperfusion injury.
AB  - Intestinal ischemia-reperfusion (IR) injury is initiated when natural IgM Abs
      recognize neo-epitopes that are revealed on ischemic cells. The target molecules
      and mechanisms whereby these neo-epitopes become accessible to recognition are
      not well understood. Proposing that isolated intestinal epithelial cells (IEC)
      may carry IR-related neo-epitopes, we used in vitro IEC binding assays to screen
      hybridomas created from B cells of unmanipulated wild-type C57BL/6 mice. We
      identified a novel IgM mAb (mAb B4) that reacted with the surface of IEC by flow
      cytometric analysis and was alone capable of causing complement activation,
      neutrophil recruitment and intestinal injury in otherwise IR-resistant Rag1(-/-)
      mice. mAb B4 was found to specifically recognize mouse annexin IV. Preinjection
      of recombinant annexin IV blocked IR injury in wild-type C57BL/6 mice,
      demonstrating the requirement for recognition of this protein to develop IR
      injury in the context of a complex natural Ab repertoire. Humans were also found
      to exhibit IgM natural Abs that recognize annexin IV. These data in toto identify
      annexin IV as a key ischemia-related target Ag that is recognized by natural Abs
      in a pathologic process required in vivo to develop intestinal IR injury.

PMID- 19380785
TI  - Developmental acquisition of the Lyn-CD22-SHP-1 inhibitory pathway promotes B
      cell tolerance.
AB  - To better understand whether autoimmunity in Lyn-deficient mice arises from
      compromised central or peripheral B cell tolerance, we examined BCR signaling
      properties of wild-type and Lyn-deficient B cells at different stages of
      development. Wild-type mature follicular B cells were less sensitive to BCR
      stimulation than were immature transitional stage 1 B cells with regard to BCR
      induced calcium elevation and ERK MAPK activation. In the absence of Lyn, mature
      B cell signaling was greatly enhanced, whereas immature B cell signaling was
      minimally affected. Correspondingly, Lyn deficiency substantially enhanced the
      sensitivity of mature B cells to activation via the BCR, but minimally affected
      events associated with tolerance induction at the immature stage. The effects of
      CD22 deficiency on BCR signaling were very similar in B cells at different stages
      of maturation. These results indicate that the Lyn-CD22-Src homology region 2
      domain-containing phosphatase-1 inhibitory pathway largely becomes operational as
      B cell mature, and sets a threshold for activation that appears to be critical
      for the maintenance of tolerance in the B cell compartment.

PMID- 19380786
TI  - Ym1/2 promotes Th2 cytokine expression by inhibiting 12/15(S)-lipoxygenase:
      identification of a novel pathway for regulating allergic inflammation.
AB  - The Ym1/2 lectin is expressed abundantly in the allergic mouse lung in an IL-13
      dependent manner. However, the role of Ym1/2 in the development of allergic
      airways disease is largely unknown. In this investigation, we show that treatment
      of mice with anti-Ym1/2 Ab during induction of allergic airways disease
      attenuated mediastinal lymph node production of IL-5 and IL-13. Ym1/2 was found
      to be expressed by dendritic cells (DCs) in an IL-13-dependent manner and
      supplementation of DC/CD4(+) T cell cocultures with Ym1/2 enhanced the ability of
      IL-13(-/-) DCs to stimulate the secretion of IL-5 and IL-13. Affinity
      chromatography identified 12/15(S)-lipoxygenase (12/15-LOX) as a Ym1/2
      interacting protein and functional studies suggested that Ym1/2 promoted the
      ability of DCs to stimulate cytokine production by inhibiting 12/15-LOX-mediated
      catalysis of 12-hydroxyeicosatetraenoic acid (12(S)-HETE). Treatment of DC/CD4(+)
      T cell cultures with the 12/15-LOX inhibitor baicalein enhanced, whereas 12(S)
      HETE inhibited the production of Th2 cytokines. Notably, delivery of 12(S)-HETE
      to the airways of mice significantly attenuated the development of allergic
      airways inflammation and the production of IL-5 and IL-13. In summary, our
      results suggest that production of Ym1/2 in response to IL-13 promotes Th2
      cytokine production and allergic airways inflammation by inhibiting the
      production of 12(S)-HETE by 12/15-LOX.

PMID- 19380787
TI  - Chronic lymphocytic leukemia and B and T cells differ in their response to cyclic
      nucleotide phosphodiesterase inhibitors.
AB  - Phosphodiesterase (PDE)4 inhibitors, which activate cAMP signaling by reducing
      cAMP catabolism, are known to induce apoptosis in B lineage chronic lymphocytic
      leukemia (CLL) cells but not normal human T cells. The explanation for such
      differential sensitivity remains unknown. In this study, we report studies
      contrasting the response to PDE4 inhibitor treatment in CLL cells and normal
      human T and B cells. Affymetrix gene chip analysis in the three cell populations
      following treatment with the PDE4 inhibitor rolipram identified a set of up
      regulated transcripts with unusually high fold changes in the CLL samples,
      several of which are likely part of compensatory negative feedback loops. The
      high fold changes were due to low basal transcript levels in CLL cells,
      suggesting that cAMP-mediated signaling may be unusually tightly regulated in
      this cell type. Rolipram treatment augmented cAMP levels and induced ATF-1/CREB
      serine 63/133 phosphorylation in both B lineage cell types but not T cells. As
      treatment with the broad-spectrum PDE inhibitor 3-isobutyl-1-methylxanthine
      induced T cell CREB phosphorylation, we tested a series of family-specific PDE
      inhibitors for their ability to mimic 3-isobutyl-1-methylxanthine-induced ATF
      1/CREB phosphorylation. Whereas PDE3 inhibitors alone had no effect, the
      combination of PDE3 and PDE4 inhibitors induced ATF-1/CREB serine 63/133
      phosphorylation in T cells. Consistent with this observation, PDE3B transcript
      and protein levels were low in CLL cells but easily detectable in T cells.
      Combined PDE3/4 inhibition did not induce T cell apoptosis, suggesting that cAMP
      mediated signal transduction that leads to robust ATF-1/CREB serine 63/133
      phosphorylation is not sufficient to induce apoptosis in this lymphoid lineage.

PMID- 19380789
TI  - Galectin-2 suppresses contact allergy by inducing apoptosis in activated CD8+ T
      cells.
AB  - Galectins, a family of structurally related beta-galactoside-binding proteins,
      are expressed by various cells of the immune systems and seem to be important for
      the regulation of immune responses and immune cell homeostasis. Since it has been
      demonstrated that galectin-2 regulates cell-mediated inflammatory bowel disease
      and colitis in mice, we intended to investigate the role of galectin-2 in
      inflammatory cutaneous T cell-mediated immune responses. To address this issue,
      groups of naive mice were sensitized to the contact allergen 2,4-dinitro-1
      fluorobenzene and systemically treated with galectin-2 to analyze the effects of
      galectin-2 on contact allergy. Here we show that galectin-2 is expressed in
      murine skin and is up-regulated upon cutaneous inflammation. Interestingly,
      treatment of mice with galectin-2 significantly reduced the contact allergy
      response. This effect was long-lasting since rechallenge of galectin-2-treated
      mice after a 14-day interval still resulted in a decreased ear swelling. We were
      able to demonstrate that galectin-2 induced a reduction of MHC class I-restricted
      immune responses in the treated animals, which was mediated by the induction of
      apoptosis specifically in activated CD8(+) T cells. Additionally, we report that
      the galectin-2-binding protein CD29 is up-regulated on the surface of activated
      CD8(+) T cells compared with naive CD8(+) T cells or CD4(+) T cells, suggesting
      that increased galectin-2/CD29 signaling might be responsible for the
      proapoptotic effects of galectin-2 on activated CD8(+) T cells. Taken together,
      these data indicate that galectin-2 may represent a novel therapeutic alternative
      for the treatment of CD8-mediated inflammatory disorders such as contact allergy.

PMID- 19380788
TI  - The regulation of liver cell survival by complement.
AB  - Complement effectors are known to contribute to host cell injury in several
      inflammatory diseases. Contrary to this paradigm, in this study utilizing
      surgical liver resection (partial hepatectomy) in various complement-deficient
      mice as a model, we have demonstrated that complement anaphylatoxins C3a and C5a
      are required for the survival of liver cells during regeneration. The mechanisms
      of these cytoprotective functions of complement were related to the regulation of
      IL-6 and TNF production or release after liver resection. Disturbances in the
      cytokine milieu, induced by a loss of complement activity, were found to alter
      prosurvival signaling, including the IL-6/STAT3 and PI3K/Akt/mammalian target of
      rapamycin pathways. In conclusion, this study documents functions of complement
      proteins as prosurvival factors that, through their interactions with cytokines,
      inhibit apoptotic signaling in proliferating cells of epithelial origin.

PMID- 19380790
TI  - Target-dependent B7-H1 regulation contributes to clearance of central nervous
      system infection and dampens morbidity.
AB  - The neurotropic coronavirus JHM strain of mouse hepatitis virus persists in
      oligodendroglia despite the presence of virus-specific CD8 T cells. Expression of
      programmed death 1 (PD-1) and B7-H1 were studied during acute and persistent
      infection to examine whether this negative regulatory mechanism contributes to
      CNS viral persistence. The majority of CNS-infiltrating CD8 T cells expressed PD
      1, with the highest levels on virus-specific CD8 T cells. Moreover, despite
      control of infectious virus, CD8 T cells within the CNS of persistently infected
      mice maintained high PD-1 expression. Analysis of virus-susceptible target cells
      in vivo revealed that B7-H1 expression was regulated in a cell type-dependent
      manner. Oligodendroglia and microglia up-regulated B7-H1 following infection;
      however, although B7-H1 expression on oligodendroglia was prominent and
      sustained, it was significantly reduced and transient on microglia. Infection of
      mice deficient in the IFN-gamma or IFN-alpha/beta receptor demonstrated that B7
      H1 expression on oligodendroglia is predominantly regulated by IFN-gamma. Ab
      blockade of B7-H1 on oligodendroglia in vitro enhanced IFN-gamma secretion by
      virus-specific CD8 T cells. More efficient virus control within the CNS of B7-H1
      deficient mice confirmed inhibition of CD8 T cell function in vivo. Nevertheless,
      the absence of B7-H1 significantly increased morbidity without altering
      demyelination. These data are the first to demonstrate glia cell type-dependent
      B7-H1 regulation in vivo, resulting in adverse effects on antiviral CD8 T cell
      function. However, the beneficial role of PD-1:B7-H1 interactions in limiting
      morbidity highlights the need to evaluate tissue-specific intervention
      strategies.

PMID- 19380791
TI  - LTbetaR signaling induces cytokine expression and up-regulates lymphangiogenic
      factors in lymph node anlagen.
AB  - The formation of lymph nodes is a complex process crucially controlled through
      triggering of LTbetaR on mesenchymal cells by LTalpha(1)beta(2) expressing
      lymphoid tissue inducer (LTi) cells. This leads to the induction of chemokines to
      attract more hematopoietic cells and adhesion molecules to retain them. In this
      study, we show that the extravasation of the first hematopoietic cells at future
      lymph node locations occurs independently of LTalpha and that these cells,
      expressing TNF-related activation-induced cytokine (TRANCE), are the earliest LTi
      cells. By paracrine signaling the first expression of LTalpha(1)beta(2) is
      induced. Subsequent LTbetaR triggering on mesenchymal cells leads to their
      differentiation to stromal organizers, which now also start to express TRANCE, IL
      7, as well as VEGF-C, in addition to the induced adhesion molecules and
      chemokines. Both TRANCE and IL-7 will further induce the expression of
      LTalpha(1)beta(2) on newly arrived immature LTi cells, resulting in more LTbetaR
      triggering, generating a positive feedback loop. Thus, LTbetaR triggering by LTi
      cells during lymph node development creates a local environment to which
      hematopoietic precursors are attracted and where they locally differentiate into
      fully mature, LTalpha(1)beta(2) expressing, LTi cells. Furthermore, the same
      signals may regulate lymphangiogenesis to the lymph node through induction of
      VEGF-C.

PMID- 19380792
TI  - A single residue, arginine 65, is critical for the functional interaction of
      leukocyte-associated inhibitory receptor-1 with collagens.
AB  - ITIM-containing receptors play an essential role in modulating immune responses.
      Leukocyte-associated inhibitory receptor (LAIR)-1, also known as CD305, is an
      ITIM-containing inhibitory receptor, expressed by all leukocytes, that binds
      collagens. In this article, we investigate the effect of a conservative R65K
      mutation on LAIR-1 ligand binding and function. Compared with LAIR-1 wild-type
      (wt)-expressing cells, LAIR-1 R65K cells show markedly reduced binding to
      collagen, which correlates with a reduced level of LAIR-1 polarization to the
      site of interaction with collagens. Both LAIR-1 wt and R65K cells can generate
      intracellular signals when ligated by anti-LAIR-1 mAb, but only LAIR-1 wt cells
      respond to collagens or matrigel. In agreement, surface plasmon resonance
      analyses showed that LAIR-1 R65K protein has markedly reduced avidity for
      collagen type I compared with LAIR-1 wt. Likewise, LAIR-1 R65K protein has
      decreased avidity for cells expressing transmembrane collagen XVII. Thus, a
      single residue, Arg65, is critical for the interaction of LAIR-1 with collagens.

PMID- 19380793
TI  - Expression of CD226 antagonizes apoptotic cell death in murine thymocytes.
AB  - CD226 is known to be expressed on many types of peripheral lymphoid cells and
      involved in T cell differentiation, activation, and cytotoxicity. In this study,
      we report that CD226 is also expressed on mouse thymocytes at varying
      developmental stages, and its expression is associated with resistance of
      thymocytes to apoptosis. The levels of CD226 expression appeared to be closely
      coupled with thymocyte development, in that it was preferentially expressed on
      CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes at all stages during mouse development,
      and was markedly increased on the cells in neonatal mice. Of the CD4(+)CD8(+)
      population, CD226 was predominantly expressed by the cells also positive for
      CD69, suggesting that CD226 expression may be induced in thymocyte-positive
      selection. Inhibition of CD226 by short hairpin RNA in a fetal thymus organ
      culture model led to reduced thymus cellularity, which was associated with
      enhanced apoptotic cell death. In contrast, CD226-transgenic mice displayed
      enlarged thymus lobes resulting from increased thymus cellularity. CD226 on
      thymocytes seemed to play a role in regulating the expression of survivin, as
      inhibition of CD226 down-regulated survivin, but overexpression of CD226 rescued
      thymocytes from apoptosis through up-regulation of survivin. In addition,
      overexpression of CD226 reduced sensitivity of EL-4 thymoma cells to apoptosis by
      up-regulating the expression of survivin. Taken together, these results indicate
      that CD226 is an antiapoptotic molecule and may play an important role in murine
      thymocyte development.

PMID- 19380794
TI  - Conditional gene targeting in mouse high endothelial venules.
AB  - High endothelial venules (HEVs) are specialized blood vessels of secondary
      lymphoid organs composed of endothelial cells with a characteristic cuboidal
      morphology. Lymphocytes selectively adhere to and migrate across HEVs to initiate
      immune responses. In this study, we established a novel transgenic mouse line
      expressing Cre recombinase under the transcriptional control of the gene encoding
      HEV-expressed sulfotransferase, N-acetylglucosamine-6-O-sulfotransferase 2
      (GlcNAc6ST-2), using bacterial artificial chromosome recombineering. Crossing
      these transgenic mice with the ROSA26 reporter strain, which expresses lacZ
      following Cre-mediated recombination, and staining the resulting progeny with 5
      bromo-4-chloro-5-indolyl-beta-D-galactoside indicated that Cre recombinase was
      specifically expressed in mAb MECA79-reactive HEVs in secondary lymphoid organs
      but not in any other blood vessels of the transgenic mice. The expression of Cre
      recombinase correlated with a developmental switch, from immature, mAb MECA367
      reactive HEVs to mature, mAb MECA79-reactive HEVs in neonatal lymph nodes. In
      addition to the HEVs, Cre recombinase was also strongly expressed in the colonic
      villi, which recapitulated the intrinsic expression of GlcNAc6ST-2 as confirmed
      in GlcNAc6ST-2(GFP/GFP) knock-in mice and by RT-PCR. Furthermore, treatment with
      an antimicrobial agent revealed that the colonic expression of Cre recombinase in
      the transgenic mice was regulated by commensal bacteria in the colon. In
      addition, Cre recombinase was expressed in a small subset of cells in the brain,
      testis, stomach, small intestine, and lung. In view of the restricted expression
      of Cre recombinase, this transgenic mouse line should be useful for elucidating
      tissue-specific gene functions using the Cre/loxP system.

PMID- 19380795
TI  - IL-4 is proangiogenic in the lung under hypoxic conditions.
AB  - IL-4-mediated proangiogenic and proinflammatory vascular responses have been
      implicated in the pathogenesis of chronic lung diseases such as asthma. Although
      it is well known that hypoxia induces pulmonary angiogenesis and vascular
      alterations, the underlying mechanism of IL-4 on the pulmonary vasculature under
      hypoxic conditions remains unknown. In this context, we designed the present
      study to determine the functional importance of IL-4 for pulmonary angiogenesis
      under hypoxic conditions using IL-4 knockout (KO) animals. Our results show that
      hypoxia significantly increased IL-4R alpha expression in wild-type (WT) control
      lungs. Even though hypoxia significantly up-regulated vascular endothelial growth
      factor (VEGF) receptor expression in the lungs of both genotypes, hypoxia-induced
      VEGF, VCAM-1, HIF-1alpha, and ERK phosphorylation were significantly diminished
      in IL-4 KO lungs as compared with WT control lungs. In addition, hypoxia-induced
      pulmonary angiogenesis and proliferating activities in the airway and pulmonary
      artery were significantly suppressed in IL-4 KO lungs as compared with WT control
      lungs. We also isolated primary lung fibroblasts from these genotypes and
      stimulated these cells with hypoxia. Hypoxia-induced VEGF production was
      significantly suppressed in lung fibroblasts from IL-4 KO mice. These in vitro
      results are in accordance with the in vivo data. Furthermore, we observed a
      significant increase of hypoxia-induced pulmonary angiogenesis in STAT6 KO mice
      similar to that in WT controls. In conclusion, IL-4 has proangiogenic properties
      in the lung under hypoxic conditions via the VEGF pathway, and this is
      independent of the STAT6 pathway.

PMID- 19380796
TI  - Cross-presentation by osteoclasts induces FoxP3 in CD8+ T cells.
AB  - Bone is remodeled throughout the life of an animal by the action of osteoclasts,
      which resorb bone, and osteoblasts, which form new bone. It has recently been
      recognized that T cells regulate osteoclasts by secreting a number of cytokines
      including type I and II IFNs and receptor activator of NF-kappaB ligand. In this
      study, we show that osteoclasts produce chemokines that recruit CD8(+) T cells.
      Using transgenic OT-I mice, we found that in the presence of OVA, osteoclasts
      induced the secretion of IL-2, IL-6, and IFN-gamma as well as the proliferation
      of CD8(+) T cells. CD8(+) T cells activated by osteoclasts expressed FoxP3,
      CTLA4, and receptor activator of NF-kappaB ligand. The FoxP3(+)CD8(+) T cells
      were anergic and suppressed dendritic cell priming of naive responder CD8(+) T
      cells. These results provide two novel observations for osteoimmunology: first,
      we demonstrate that osteoclasts can cross-present Ags to CD8(+) T cells. Second,
      these data show that osteoclasts are not only regulated by T cells, but they also
      can regulate T cells forming a feedback control loop. The induction of FoxP3 in T
      cells through a MHC class I-dependent manner provides a new mechanism to
      peripherally produce a regulatory T cell. These observations open a new avenue of
      investigation for the pathogenesis of autoimmune-mediated inflammatory bone
      diseases.

PMID- 19380797
TI  - Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal
      interface during early human pregnancy.
AB  - Regulatory T cells (Treg) expand during pregnancy and are present at the fetal
      maternal interface at very early stages in pregnancy. The migration mechanisms of
      Treg to the pregnant uterus are still unclear. Human chorionic gonadotropin (hCG)
      is secreted by the blastocyst immediately after fertilization and has
      chemoattractant properties. Therefore, we sought to analyze whether hCG secreted
      by early trophoblasts attracts Treg to the uterus and hence contributes to
      maternal tolerance toward the fetus. Decidua and placenta tissue samples from
      patients having spontaneous abortions or ectopic pregnancies were employed to
      evaluate Treg and hCG levels. Age-matched samples from normal pregnant women
      served as controls. We further performed in vitro studies with primary first
      trimester trophoblast cells and a choriocarcinoma cell line (JEG-3) aiming to
      evaluate the ability of secreted hCG to attract Treg. Patients having
      miscarriages or ectopic pregnancy presented significantly decreased hCG mRNA and
      protein levels associated with decreased Foxp3, neuropilin-1, IL-10, and TGF-beta
      mRNA levels as compared with normal pregnant women. Using migration assays we
      demonstrated that Treg were attracted by hCG-producing trophoblasts or
      choriocarcinoma cells. Treg migration toward cells transfected with hCG
      expression vectors confirmed the chemoattractant ability of hCG. Our data clearly
      show that hCG produced by trophoblasts attracts Treg to the fetal-maternal
      interface. High hCG levels at very early pregnancy stages ensure Treg to migrate
      to the site of contact between paternal Ags and maternal immune cells and to
      orchestrate immune tolerance toward the fetus.

PMID- 19380798
TI  - Oncoprotein signaling mediates tumor-specific inflammation and enhances tumor
      progression.
AB  - The RET/PTC3 (RP3) fusion protein is an oncogene expressed during the development
      of thyroid cancer and in thyroid epithelial cells of patients with Hashimoto's
      thyroiditis. RP3 has two immunological properties: 1) it encodes a chimeric
      protein including peptides that may be targets of antitumor immune responses and
      2) it is a tyrosine kinase that can activate NF-kappaB transcriptional programs,
      induce secretion of proinflammatory mediators, and stimulate innate immunity. To
      distinguish the antigenic properties of the RP3 oncoprotein from its signaling
      function, a transplantable tumor system was developed. Tumors expressing the
      functional, but not mutant, form of RP3 show enhanced infiltration of CD8(+)
      lymphocytes, myeloid-derived CD11b(+)Gr1(+) cells, and enhanced growth in
      immunocompetent mice. In contrast, RP3 signaling mutant-expressing tumors
      maintained enhanced infiltration of CD8(+) lymphocytes did not enhance
      recruitment of CD11b(+)Gr1(+) cells and showed a decreased tumor incidence. These
      results implicate a role for RP3 function in enhancing a tumor-suppressive innate
      inflammatory response. These experiments support a mechanism whereby oncogenes
      can directly recruit and activate innate and adaptive immune cells, resulting in
      enhanced tumor progression.

PMID- 19380799
TI  - Bone marrow-derived mast cells accumulate in the central nervous system during
      inflammation but are dispensable for experimental autoimmune encephalomyelitis
      pathogenesis.
AB  - Reports showing that W/W(v) mice are protected from experimental autoimmune
      encephalomyelitis (EAE, a murine model of multiple sclerosis), have implicated
      mast cells as an essential component in disease susceptibility, but the role of
      mast cell trafficking has not been addressed. In this study, we have used both
      mast cell transplantation and genetic mutations (Cd34(-/-), W/W(v), W(sh)/W(sh))
      to investigate the role of mast cell trafficking in EAE in detail. We show, for
      the first time, that bone marrow-derived mast cells are actively recruited to the
      CNS during EAE. Unexpectedly, however, we found that EAE develops unabated in two
      independent genetic backgrounds in the complete absence of mast cells or bone
      marrow-derived mast cell reconstitution. We conclude that although mast cells do
      accumulate in the brain and CNS during demyelinating disease via peripheral mast
      cell trafficking, they are completely dispensable for development of disease.

PMID- 19380800
TI  - Impaired CD4 and CD8 effector function and decreased memory T cell populations in
      ICOS-deficient patients.
AB  - Interaction of ICOS with its ligand is essential for germinal center formation, T
      cell immune responses, and development of autoimmune diseases. Human ICOS
      deficiency has been identified worldwide in nine patients with identical ICOS
      mutations. In vitro studies of the patients to date have shown only mild T cell
      defect. In this study, we report an in-depth analysis of T cell function in two
      siblings with novel ICOS deficiency. The brother displayed mild skin infections
      and impaired Ig class switching, whereas the sister had more severe symptoms,
      including immunodeficiency, rheumatoid arthritis, inflammatory bowel disease,
      interstitial pneumonitis, and psoriasis. Despite normal CD3/CD28-induced
      proliferation and IL-2 production in vitro, peripheral blood T cells in both
      patients showed a decreased percentage of CD4 central and effector memory T cells
      and impaired production of Th1, Th2, and Th17 cytokines upon CD3/CD28
      costimulation or PMA/ionophore stimulation. The defective polarization into
      effector cells was associated with impaired induction of T-bet, GATA3, MAF, and
      retinoic acid-related orphan nuclear hormone receptor (RORC). Reduced CTLA
      4(+)CD45RO(+)FoxP3(+) regulatory T cells and diminished induction of inhibitory
      cell surface molecules, including CTLA-4, were also observed in the patients. T
      cell defect was not restricted to CD4 T cells because reduced memory T cells and
      impaired IFN-gamma production were also noted in CD8 T cells. Further analysis of
      the patients demonstrated increased induction of receptor activator of NF-kappaB
      ligand (RANKL), lack of IFN-gamma response, and loss of Itch expression upon
      activation in the female patient, who had autoimmunity. Our study suggests that
      extensive T cell dysfunction, decreased memory T cell compartment, and imbalance
      between effector and regulatory cells in ICOS-deficient patients may underlie
      their immunodeficiency and/or autoimmunity.

PMID- 19380801
TI  - Impact of intrinsic cooperative thermodynamics of peptide-MHC complexes on
      antiviral activity of HIV-specific CTL.
AB  - The antiviral activity of HIV-specific CTL is not equally potent but rather is
      dependent on their specificity. But what characteristic of targeted peptides
      influences CTL antiviral activity remains elusive. We addressed this issue based
      on HLA-B35-restricted CTLs specific for two overlapping immunodominant Nef
      epitopes, VY8 (VPLRPMTY) and RY11 (RPQVPLRPMTY). VY8-specific CTLs were more
      potently cytotoxic toward HIV-infected primary CD4(+) cells than RY11-specific
      CTLs. Reconstruction of their TCR revealed no substantial difference in their
      functional avidity toward cognate Ags. Instead, the decay analysis of the peptide
      MHC complex (pMHC) revealed that the VY8/HLA-B35 complex could maintain its
      capacity to sensitize T cells much longer than its RY11 counterpart.
      Corroboratively, the introduction of a mutation in the epitopes that
      substantially delayed pMHC decay rendered Nef-expressing target cells more
      susceptible to CTL killing. Moreover, by using differential scanning calorimetry
      and circular dichroism analyses, we found that the susceptible pMHC ligands for
      CTL killing showed interdependent and cooperative, rather than separate or
      sequential, transitions within their heterotrimer components under the thermally
      induced unfolding process. Collectively, our results highlight the significant
      effects of intrinsic peptide factors that support cooperative thermodynamics
      within pMHC on the efficient CTL killing of HIV-infected cells, thus providing us
      better insight into vaccine design.

PMID- 19380802
TI  - An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1
      Listeria monocytogenes anti-angiogenesis cancer vaccine for the treatment of
      primary and metastatic Her-2/neu+ breast tumors in a mouse model.
AB  - Thirty years after angiogenesis was shown to play an enabling role in cancer,
      modern medicine is still trying to develop novel compounds and therapeutics to
      target the tumor vasculature. However, most therapeutics require multiple rounds
      of administration and can have toxic side effects. In this study, we use anti
      angiogenesis immunotherapy to target cells actively involved in forming new blood
      vessels that support the growth and spread of breast cancer. Targeting a central
      cell type involved in angiogenesis, endothelial cells, we immunized against host
      vascular endothelial growth factor receptor 2 to fight the growth of Her-2/neu(+)
      breast tumors. Using the bacterial vector, Listeria monocytogenes (Lm), we fused
      polypeptides from the mouse vascular endothelial growth factor receptor 2
      molecule (fetal liver kinase-1) to the microbial adjuvant, listeriolysin-O, and
      used Lm to deliver the Ags and elicit potent antitumor CTL responses. Lm
      listeriolysin-O-fetal liver kinase-1 was able to eradicate some established
      breast tumors, reduce microvascular density in the remaining tumors, protect
      against tumor rechallenge and experimental metastases, and induce epitope
      spreading to various regions of the tumor-associated Ag Her-2/neu. Tumor
      eradication was found to be dependent on epitope spreading to HER-2/neu and was
      not solely due to the reduction of tumor vasculature. However, vaccine efficacy
      did not affect normal wound healing nor have toxic side effects on pregnancy. We
      show that an anti-angiogenesis vaccine can overcome tolerance to the host
      vasculature driving epitope spreading to an endogenous tumor protein and drive
      active tumor regression.

PMID- 19380803
TI  - TLR agonists prevent the establishment of allogeneic hematopoietic chimerism in
      mice treated with costimulation blockade.
AB  - Activation of TLR4 by administration of LPS shortens the survival of skin
      allografts in mice treated with costimulation blockade through a CD8 T cell
      dependent, MyD88-dependent, and type I IFN receptor-dependent pathway. The effect
      of TLR activation on the establishment of allogeneic hematopoietic chimerism in
      mice treated with costimulation blockade is not known. Using a costimulation
      blockade protocol based on a donor-specific transfusion (DST) and a short course
      of anti-CD154 mAb, we show that LPS administration at the time of DST matures
      host alloantigen-presenting dendritic cells, prevents the establishment of mixed
      allogeneic hematopoietic chimerism, and shortens survival of donor-specific skin
      allografts. LPS mediates its effects via a mechanism that involves both CD4(+)
      and CD8(+) T cells and results from signaling through either the MyD88 or the
      type I IFN receptor pathways. We also document that timing of LPS administration
      is critical, as injection of LPS 24 h before treatment with DST and anti-CD154
      mAb does not prevent hematopoietic engraftment but administration the day after
      bone marrow transplantation does. We conclude that TLR4 activation prevents the
      induction of mixed allogeneic hematopoietic chimerism through type I IFN receptor
      and MyD88-dependent signaling, which leads to the up-regulation of costimulatory
      molecules on host APCs and the generation of alloreactive T cells. These data
      suggest that distinct but overlapping cellular and molecular mechanisms control
      the ability of TLR agonists to block tolerance induction to hematopoietic and
      skin allografts in mice treated with costimulation blockade.

PMID- 19380804
TI  - Rapid up-regulation and granule-independent transport of perforin to the
      immunological synapse define a novel mechanism of antigen-specific CD8+ T cell
      cytotoxic activity.
AB  - CTL are endowed with the ability to eliminate pathogens through perforin-mediated
      cytotoxic activity. The mechanism for perforin-mediated Ag-specific killing has
      been solely attributed to cytotoxic granule exocytosis from activated CD8(+) T
      cells. In this study, we redefine this mechanism, demonstrating that virus
      specific CD8(+) T cells rapidly up-regulate perforin in response to stimulation
      temporally with IFN-gamma and CD107a expression. Following Ag-specific
      activation, newly synthesized perforin rapidly appears at the immunological
      synapse, both in association with and independent of cytotoxic granules, where it
      functions to promote cytotoxicity. Our work suggests a novel mechanism of CTL
      cytotoxicity and identifies a novel correlate of CD8(+) T cell-mediated immunity.

PMID- 19380805
TI  - Molecular dissection of antibody responses against pneumococcal surface protein
      A: evidence for diverse DH-less heavy chain gene usage and avidity maturation.
AB  - Immunization of human volunteers with a single dose of pneumococcal surface
      protein A (PspA) stimulates broad cross-reactive Abs to heterologous PspA
      molecules that, when transferred, protect mice from fatal infection with
      Streptococcus pneumoniae. In this study, we report the molecular characterization
      of 36 mouse mAbs generated against the extracellular domain of PspA (PspA(3-286))
      from strain R36A. Abs to PspA(3-286) were encoded by diverse V(H) and V(kappa)
      families/genes. The H chain CDR3 and L chain CDR3 lengths were 3-13 (7.8 +/- 0.5)
      and 8-9 (8.7 +/- 0.2) codons, respectively. Unexpectedly, seven hybridomas
      expressed H chains that lack D(H) gene-derived amino acids. Nontemplate-encoded
      addition(s) were observed in the H chain expressed in six of these seven
      hybridomas; Palindromic addition(s) were absent. Absence of D(H) gene-derived
      amino acids did not prevent anti-PspA(3-286) mAbs from attaining average relative
      avidity. Avidity maturation occurred during primary IgG anti-PspA(3-286)
      polyclonal Ab response in PspA(3-286)- and R36A-immunized mice. Compared with
      PspA(3-286)-immunized mice, the relative avidity of the primary polyclonal IgG
      Abs was higher in R36A immunized mice on days 72, 86, and 100. Two pairs of
      clonally related hybridomas were observed. D(H) genes expressed in the majority
      (75.9%) of the hybridomas used reading frame 3. Analysis of replacement/silent
      mutation ratio in the CDR and framework regions provided evidence for Ag-driven
      selection in 11 mAbs. Based on epitope localization experiments, the mAbs were
      classified into 12 independent groups. ELISA additivity assay indicated that
      members within a group recognized topographically related epitopes. This study
      provides molecular insights into the biology of D(H)-less Abs.

PMID- 19380806
TI  - Assembled DJ beta complexes influence TCR beta chain selection and peripheral V
      beta repertoire.
AB  - TCRbeta chain repertoire of peripheral alphabeta T cells is generated through the
      stepwise assembly and subsequent selection of TCRbeta V region exons during
      thymocyte development. To evaluate the influence of a two-step recombination
      process on Vbeta rearrangement and selection, we generated mice with a
      preassembled Dbeta1Jbeta1.1 complex on the Jbeta1(omega) allele, an endogenous
      TCRbeta allele that lacks the Dbeta2-Jbeta2 cluster, creating the Jbeta1(DJbeta)
      allele. As compared with Jbeta1(omega/omega) mice, both Jbeta1(DJbeta/omega) and
      Jbeta1(DJbeta/DJbeta) mice exhibited grossly normal thymocyte development and
      TCRbeta allelic exclusion. In addition, Vbeta rearrangements on Jbeta1(DJbeta)
      and Jbeta1(omega) alleles were similarly regulated by TCRbeta-mediated feedback
      regulation. However, in-frame VbetaDJbeta rearrangements were present at a higher
      level on the Jbeta1(DJbeta) alleles of Jbeta1(DJbeta/omega) alphabeta T cell
      hybridomas, as compared with on the Jbeta1(omega) alleles. This bias was most
      likely due to both an increased frequency of Vbeta-to-DJbeta rearrangements on
      Jbeta1(DJbeta) alleles and a preferential selection of cells with in-frame
      VbetaDJbeta exons assembled on Jbeta1(DJbeta) alleles during the development of
      Jbeta1(DJbeta/omega) alphabeta T cells. Consistent with the differential
      selection of in-frame VbetaDJbeta rearrangements on Jbeta1(DJbeta) alleles, the
      Vbeta repertoire of alphabeta T cells was significantly altered during alphabeta
      TCR selection in Jbeta1(DJbeta/omega) and Jbeta1(DJbeta/DJbeta) mice, as compared
      with in Jbeta1(omega/omega) mice. Our data indicate that the diversity of DJbeta
      complexes assembled during thymocyte development influences TCRbeta chain
      selection and peripheral Vbeta repertoire.

PMID- 19380807
TI  - The essential role of LAT in thymocyte development during transition from the
      double-positive to single-positive stage.
AB  - The linker for activation of T cells (LAT) is an adaptor protein that couples TCR
      engagement to downstream signaling cascades. LAT is important in early thymocyte
      development as LAT-deficient mice have a complete block at the double-negative
      (DN) 3 stage. To study the role of LAT beyond the DN3 stage, we generated mice in
      which the lat gene could be deleted by the Cre recombinase. Analysis of these
      mice showed that deletion of LAT after the DN3 stage allowed thymocytes to
      develop past the DN3 to DN4 checkpoint and to generate double-positive
      thymocytes. However, LAT-deficient DP thymocytes were severely defective in
      responding to stimulation via the TCR and failed to differentiate into single
      positive thymocytes efficiently. Consequently, few LAT-deficient mature T cells
      could be found in the periphery. These T cells had undergone extensive
      homeostatic proliferation and expressed low levels of the TCR on their surface.
      Collectively, our data indicate that in addition to its role in pre-TCR
      signaling, LAT also plays an essential role in thymocyte development during
      transition from the double-positive to single-positive stage.

PMID- 19380809
TI  - IL-6 modulates CD5 expression in B cells from patients with lupus by regulating
      DNA methylation.
AB  - B lymphocytes from patients with systemic lupus erythematosus (SLE) are
      characterized by reduced expression levels of membrane CD5. Recent studies from
      our laboratory have revealed that the level of membrane CD5 is determined by the
      relative level of two alternative CD5 isoforms; CD5-E1A, which is expressed on
      the membrane, and CD5-E1B, which is retained in the cytoplasm. Using bisulfite
      sequencing and methylation-sensitive endonuclease assays we show that the
      promoter for the alternative CD5-E1B isoform is demethylated in B cells from
      patients with SLE but not in healthy controls. We go on to show that differential
      methylation is more pronounced following BCR engagement. As a result of this
      demethylation, CD5-E1B mRNA is transcribed at the expense of CD5-E1A mRNA
      transcription. We provide further evidence that production of high IL-6 levels by
      SLE B cells abrogates the ability of SLE B cells to induce DNA methyl transferase
      (DNMT1) and then to methylate DNA, an effect that is reversed in the presence of
      a blocking Ab to the IL-6 receptor. The pattern of demethylation of CpG islands
      in the CD5-E1B promoter in SLE B cells is similar to those in B cells from
      healthy controls stimulated in the presence of IL-6, or treated with the
      methylation inhibitor PD98059. The study reveals that engagement of the BCR with
      constitutive IL-6 down-regulates the level of membrane CD5, which negatively
      regulates BCR signaling, in SLE B cells. This altered signaling could, in turn,
      promote the activation and expansion of autoreactive B cells in SLE patients.

PMID- 19380808
TI  - Patterns of receptor revision in the immunoglobulin heavy chains of a teleost
      fish.
AB  - H chain cDNA libraries were constructed from the RNA derived from seven different
      organs and tissues from the same individual catfish. Sequence analysis of >300
      randomly selected clones identified clonal set members within the same or
      different tissues, and some of these represented mosaic or hybrid sequences.
      These hybrids expressed V(H) members of the same or different V(H) families
      within different regions of the same clone. Within some clonal sets multiple
      hybrids were identified, and some of these represented the products of sequential
      V(H) replacement events. Different experimental methods confirmed that hybrid
      clones identified in the cDNA library from one tissue could be reisolated in the
      cDNA pool or from the total RNA derived from the same or a different tissue,
      indicating that these hybrids likely represented the products of in vivo receptor
      revision events. Murine statistical recombination models were used to evaluate
      cryptic recombination signal sequences (cRSS), and significant cRSS pairs in the
      predicted V(H) donor and recipient were identified. These models supported the
      hypothesis that seamless revisions may have occurred via hybrid joint formation.
      The heptamers of the cRSS pairs were located at different locations within the
      coding region, and different events resulted in the replacement of one or both
      CDR as well as events that replaced the upstream untranslated region and the
      leader region. These studies provide phylogenetic evidence that receptor revision
      may occur in clonally expanded B cell lineages, which supports the hypothesis
      that additional levels of somatic H chain diversification may exist.

PMID- 19380810
TI  - Direct hematological toxicity and illegitimate chromosomal recombination caused
      by the systemic activation of CreERT2.
AB  - The CreER(T2) for conditional gene inactivation has become increasingly used in
      reverse mouse genetics, which enables temporal regulation of Cre activity using a
      mutant estrogen binding domain (ER(T2)) to keep Cre inactive until the
      administration of tamoxifen. In this study, we present the severe toxicity of
      ubiquitously expressed CreER(T2) in adult mice and embryos. The toxicity of Cre
      recombinase or CreER(T2) in vitro or in vivo organisms are still less
      sufficiently recognized considering the common use of Cre/loxP system, though the
      toxicity might compromise the phenotypic analysis of the gene of interest. We
      analyzed two independent lines in which CreER(T2) is knocked-in into the Rosa26
      locus (R26CreER(T2) mice), and both lines showed thymus atrophy, severe anemia,
      and illegitimate chromosomal rearrangement in hematopoietic cells after the
      administration of tamoxifen, and demonstrated complete recovery of hematological
      toxicity in adult mice. In the hematopoietic tissues in R26CreER(T2) mice,
      reduced proliferation and increased apoptosis was observed after the
      administration of tamoxifen. Flow cytometric analysis revealed that CreER(T2)
      toxicity affected several hematopoietic lineages, and that immature cells in
      these lineages tend to be more sensitive to the toxicity. In vitro culturing of
      hematopoietic cells from these mice further demonstrated the direct toxicity of
      CreER(T2) on growth and differentiation of hematopoietic cells. We further
      demonstrated the cleavage of the putative cryptic/pseudo loxP site in the genome
      after the activation of CreER(T2) in vivo. We discussed how to avoid the
      misinterpretation of the experimental results from potential toxic effects due to
      the activated CreER(T2).

PMID- 19380811
TI  - Transcriptome profiling and functional analyses of the zebrafish embryonic innate
      immune response to Salmonella infection.
AB  - Due to the clear separation of innate immunity from adaptive responses, the
      externally developing zebrafish embryo represents a useful in vivo model for
      identification of innate host determinants of the response to bacterial
      infection. Here we performed a time-course transcriptome profiling study and gene
      ontology analysis of the embryonic innate immune response to infection with two
      model Salmonella strains that elicit either a lethal infection or an attenuated
      response. The transcriptional response to infection with both the lethal strain
      and the avirulent LPS O-Ag mutant strain showed clear conservation with host
      responses detected in other vertebrate models and human cells, including
      induction of genes encoding cell surface receptors, signaling intermediates,
      transcription factors, and inflammatory mediators. Furthermore, our study led to
      the identification of a large set of novel immune response genes and infection
      markers, the future functional characterization of which will support vertebrate
      genome annotation. From the time series and bacterial strain comparisons, matrix
      metalloproteinase genes, including mmp9, were among the most consistent infection
      responsive genes. Purified Salmonella flagellin also strongly induced mmp9
      expression. Using knockdown analysis, we showed that this gene was downstream of
      the zebrafish homologs of the flagellin receptor TLR5 and the adaptor MyD88.
      Additionally, flagellin-mediated induction of other inflammation markers,
      including il1b, il8, and cxcl-C1c, was reduced upon Tlr5 knockdown as well as
      expression of irak3, a putative negative TLR pathway regulator. Finally, we
      showed that induction of il1b, mmp9, and irak3 requires Myd88-dependent
      signaling, while ifn1 and il8 were induced Myd88 independently during Salmonella
      infection.

PMID- 19380812
TI  - Phagocytosis in macrophages lacking Cbl reveals an unsuspected role for Fc gamma
      receptor signaling and actin assembly in target binding.
AB  - Fc gamma receptor (Fc gammaR)-mediated phagocytosis is known to require tyrosine
      kinases (TKs). We identified c-Cbl and Cbl-b as proteins that undergo tyrosine
      phosphorylation during phagocytosis. Cbl-deficient macrophages displayed enhanced
      Fc gammaR-mediated signaling and phagocytosis. Surprisingly, binding of IgG
      coated targets (EIgG) was also enhanced. c-Cbl-deficient macrophages expressed
      less Fc gammaRIIb, the inhibitory Fc gamma receptor; however, this did not
      account for enhanced target binding. We isolated the function of one Fc receptor
      isoform, Fc gammaRI, using IgG2a-coated targets (EIgG2a). Cbl-deficient
      macrophages demonstrated a disproportionate increase in binding EIgG2a,
      suggesting that signal strength regulates binding efficiency toward opsonized
      targets. In resting cells, Fc gammaRI colocalized with the Src family TK Hck in F
      actin-rich structures, which was enhanced in Cbl-deficient macrophages. Target
      binding was sensitive to TK inhibitors, profoundly inhibited following depletion
      of cholesterol, and ablated at 4 degrees C or in the presence of inhibitors of
      actin polymerization. Sensitivity of EIgG binding to cytoskeletal disruption was
      inversely proportional to opsonin density. These findings challenge the view that
      Fc gammaR-mediated binding is a passive event. They suggest that dynamic
      engagement of TKs and the cytoskeleton enables macrophages to serve as cellular
      "Venus fly traps", with the capacity to capture phagocytic targets under
      conditions of limiting opsonin density.

PMID- 19380814
TI  - A proviral role for CpG in cytomegalovirus infection.
AB  - TLR9-dependent signaling in plasmacytoid dendritic cells is a key contributor to
      innate immune defense to mouse CMV infection. We aimed to study the expression
      and potential contribution of TLR9 signaling in human CMV (HCMV) infection of
      primary fibroblasts. HCMV infection strongly induced TLR9 expression in two of
      three fibroblast types tested. Furthermore, the TLR9 ligand CpG-B induced a
      strong proviral effect when added shortly after HCMV infection, enhancing virus
      production and cell viability. However, not all CpG classes displayed proviral
      activity, and this correlated with their IFN-beta-inducing ability. The proviral
      effect of CpG-B correlated completely with concurrent viral up-regulation of TLR9
      in fibroblasts. Importantly, the timing of CpG addition was a critical parameter;
      in striking contrast to the proviral effect, CpG addition at the time of
      infection blocked viral uptake and nearly abolished HCMV production. The
      contrasting and time-dependent effects of CpG on HCMV infectivity reveal a
      complex interplay between CpG, TLR9, and HCMV infection. Additionally, the data
      suggest a potentially harmful role for CpG in the promotion of HCMV infection.

PMID- 19380813
TI  - Gastrointestinal nematode infection exacerbates malaria-induced liver pathology.
AB  - Mixed parasite infections are common in many parts of the world, but little is
      known of the effects of concomitant parasite infections on the immune response or
      severity of clinical disease. We have used the nonlethal malaria infection model
      of Plasmodium chabaudi AS in combination with the gastrointestinal nematode
      Heligmosomoides bakeri polygyrus to investigate the impact of nematode infections
      on malarial morbidity and antimalarial immunity. The data demonstrate that wild
      type C57BL/6 mice coinfected with both parasites simultaneously exhibit a
      striking increase in mortality, while mice deficient in IFN-gamma or IL-23
      survive coinfection. The increase in mortality in wild-type mice was associated
      with severe liver pathology characterized by extensive coagulative necrosis and
      an increase in hepatic IFN-gamma, IL-17, and IL-22 mRNA expression. This is the
      first demonstration of increased malaria-associated pathology associated with a
      switch toward a proinflammatory environment, involving not only IFN-gamma but
      also the IL-17/IL-23 axis, as a result of coinfection with a gastrointestinal
      helminth.

PMID- 19380815
TI  - Actin and RIG-I/MAVS signaling components translocate to mitochondria upon
      influenza A virus infection of human primary macrophages.
AB  - Influenza A virus is one of the most important causes of respiratory infection.
      During viral infection, multiple cell signaling cascades are activated, resulting
      in the production of antiviral cytokines and initiation of programmed cell death
      of virus-infected cells. In the present study, we have used subcellular
      proteomics to reveal the host response to influenza A infection at the protein
      level in human macrophages. Macrophages were infected with influenza A virus,
      after which the cytosolic and mitochondrial cell fractions were prepared and
      analyzed by using two-dimensional electrophoresis for protein separation and mass
      spectrometry for protein identification. In cytosolic proteomes, the level of
      several heat shock proteins and fragments of cytoskeletal proteins was clearly up
      regulated during influenza A virus infection. In mitochondrial proteomes,
      simultaneously with the expression of viral proteins, the level of intact actin
      and tubulin was highly up-regulated. This was followed by translocation of the
      components of antiviral RNA recognition machinery, including RIG-I (retinoic acid
      inducible protein I), TRADD (TNFR1-associated death domain protein), TRIM25
      (tripartite motif protein 25), and IKKepsilon (inducible IkappaB kinase), onto
      the mitochondria. Cytochalasin D, a potent inhibitor of actin polymerization,
      clearly inhibited influenza A virus-induced expression of IFN-beta, IL-29, and
      TNF-alpha, suggesting that intact actin cytoskeleton structure is crucial for
      proper activation of antiviral response. At late phases of infection
      mitochondrial fragmentation of actin was seen, indicating that actin fragments,
      fractins, are involved in disruption of mitochondrial membranes during apoptosis
      of virus-infected cells. In conclusion, our results suggest that actin network
      interacts with mitochondria to regulate both antiviral and cell death signals
      during influenza A virus infection.

PMID- 19380816
TI  - Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived
      suppressor cells.
AB  - Myeloid-derived suppressor cells (MDSC) are a major component of the immune
      suppressive network described in cancer and many other pathological conditions.
      Recent studies have demonstrated that one of the major mechanisms of MDSC-induced
      immune suppression is mediated by reactive oxygen species (ROS). However, the
      mechanism of this phenomenon remained unknown. In this study, we observed a
      substantial up-regulation of ROS by MDSC in all of seven different tumor models
      and in patients with head and neck cancer. The increased ROS production by MDSC
      is mediated by up-regulated activity of NADPH oxidase (NOX2). MDSC from tumor
      bearing mice had significantly higher expression of NOX2 subunits, primarily
      p47(phox) and gp91(phox), compared with immature myeloid cells from tumor-free
      mice. Expression of NOX2 subunits in MDSC was controlled by the STAT3
      transcription factor. In the absence of NOX2 activity, MDSC lost the ability to
      suppress T cell responses and quickly differentiated into mature macrophages and
      dendritic cells. These findings expand our fundamental understanding of the
      biology of MDSC and may also open new opportunities for therapeutic regulation of
      these cells in cancer.

PMID- 19380817
TI  - IL-7 receptor expression provides the potential for long-term survival of both
      CD62Lhigh central memory T cells and Th1 effector cells during Leishmania major
      infection.
AB  - Infection with the intracellular protozoan parasite Leishmania major induces a
      state of concomitant immunity wherein secondary immunity is dependent upon the
      persistence of the original pathogen. Our laboratory has described two
      populations of Leishmania-induced CD4(+) T cells that contribute to immunity:
      CD62L(high) central memory T (T(CM)) cells and CD62L(low) effector T cells. To
      determine whether the prosurvival cytokine IL-7 contributes to maintaining these
      T cells, we examined expression of the IL7R on CD4(+) T cells activated during L.
      major infection. We found that T(CM) cells present in chronically infected mice
      expressed high levels of the IL7R. However, in addition to the expression of the
      IL7R by T(CM) cells, CD62L(low) cells responding to L. major infection expressed
      the IL7R. Additional experiments revealed that a large percentage of the
      IL7R(high)CD62L(low) cells were Th1 cells, based on transcription at the IFN
      gamma locus and up-regulation of the Th1-promoting transcription factor T-bet.
      The up-regulation of T-bet did not prevent IL7R expression by L. major-responding
      CD4(+) T cells, nor did the absence of T-bet result in increased IL7R expression.
      Finally, blockade of IL7R signaling decreased the number of T-bet(+)CD4(+) T
      cells, reduced IFN-gamma production, and inhibited delayed-type hypersensitivity
      responses in immune mice challenged with L. major, indicating that IL7R signaling
      contributes to the maintenance of Th1 effector cells. Thus, both T(CM) and Th1
      effector cells can express the IL7R during chronic L. major infection, which
      provides a potential means for their long-term survival in addition to the
      presence of persisting parasites.

PMID- 19380818
TI  - The innate immune response affects the development of the autoimmune response in
      Theiler's virus-induced demyelinating disease.
AB  - Multiple sclerosis (MS) is a human CNS autoimmune demyelinating disease.
      Epidemiological evidence has suggested a role for virus infection in the
      initiation and/or exacerbation of MS. Theiler's murine encephalomyelitis virus
      (TMEV)-induced demyelinating disease serves as a relevant mouse model for MS.
      TMEV-infected mice develop a demyelinating disease with clinical symptoms
      beginning around 35 days after infection, which is associated with development of
      myelin-specific, PLP(139-151), CD4(+) T cell responses. Viruses have been
      suggested to initiate autoimmune disease through bystander activation of immune
      cells or through bystander damage to tissue during infection. We examined the
      effect of the innate immune response on development of autoimmune demyelinating
      disease by altering the innate immune response through administration of innate
      immune cytokines, IFN-alpha or IFN-beta, or antiserum against the type I IFNs
      during the innate immune response to TMEV. Administration of IFN-beta, but not
      IFN-alpha, to TMEV- infected mice led to reduced myelin-specific CD4(+) T cell
      responses and reduced demyelinating disease, which was associated with decreased
      immune cell infiltration into the CNS and increased expression of IL-10 in the
      CNS. Conversely, administration of antiserum to IFN-beta led to a more severe
      demyelinating disease. In addition, administration of poly(I:C), which is an
      innate immune agonist, to TMEV-infected mice during the innate immune response
      resulted in decreased myelin-specific CD4(+) T cell responses and reduced
      demyelinating disease. These results demonstrate that activating or enhancing the
      innate immune response can reduce the subsequent initiation and progression of
      the autoimmune response and demyelinating disease.

PMID- 19380819
TI  - The avidity and lytic efficiency of the CTL response to HTLV-1.
AB  - In human T-lymphotropic virus type 1 (HTLV-1) infection, a high frequency of HTLV
      1-specific CTLs can co-exist stably with a high proviral load and the proviral
      load is strongly correlated with the risk of HTLV-1-associated inflammatory
      diseases. These observations led to the hypothesis that HTLV-1 specific CTLs are
      ineffective in controlling HTLV-1 replication but contribute to the pathogenesis
      of the inflammatory diseases. But evidence from host and viral immunogenetics and
      gene expression microarrays suggests that a strong CTL response is associated
      with a low proviral load and a low risk of HAM/TSP. Here, we quantified the
      frequency, lytic activity and functional avidity of HTLV-1-specific CD8(+) cells
      in fresh, unstimulated PBMCs from individuals with natural HTLV-1 infection. The
      lytic efficiency of the CD8(+) T cell response-the fraction of autologous HTLV-1
      expressing cells eliminated per CD8(+) cell per day-was inversely correlated with
      both the proviral load and the rate of spontaneous proviral expression. The
      functional avidity of HTLV-1-specific CD8(+) cells was strongly correlated with
      their lytic efficiency. We conclude that efficient control of HTLV-1 in vivo
      depends on the CTL lytic efficiency, which depends in turn on CTL avidity of Ag
      recognition. CTL quality determines the position of virus-host equilibrium in
      persistent HTLV-1 infection.

PMID- 19380820
TI  - Pertussis toxin signals through the TCR to initiate cross-desensitization of the
      chemokine receptor CXCR4.
AB  - Pertussis toxin (PTx) has been shown to exert a variety of effects on immune
      cells independent of its ability to ADP-ribosylate G proteins. Of these effects,
      the binding subunit of PTx (PTxB) has been shown to block signaling via the
      chemokine receptor CCR5, but the mechanism involved in this process is unknown.
      Here, we show that PTxB causes desensitization of a related chemokine receptor,
      CXCR4, and explore the mechanism by which this occurs. CXCR4 is the receptor for
      the chemokine stromal cell-derived factor 1alpha (SDF-1alpha) and elicits a
      number of biological effects, including stimulation of T cell migration. PTxB
      treatment causes a decrease in CXCR4 surface expression, inhibits G protein
      associated signaling, and blocks SDF-1alpha-mediated chemotaxis. We show that
      PTxB mediates these effects by activating the TCR signaling network, as the
      effects are dependent on TCR and ZAP70 expression. Additionally, the activation
      of the TCR with anti-CD3 mAb elicits a similar set of effects on CXCR4 activity,
      supporting the idea that TCR signaling leads to cross-desensitization of CXCR4.
      The inhibition of CXCR4 by PTxB is rapid and transient; however, the catalytic
      activity of PTx prevents CXCR4 signaling in the long term. Thus, the effects of
      PTx holotoxin on CXCR4 signaling can be divided into two phases: short term by
      the B subunit, and long term by the catalytic subunit. These data suggest that
      TCR crosstalk with CXCR4 is likely a normal cellular process that leads to cross
      desensitization, which is exploited by the B subunit of PTx.

PMID- 19380821
TI  - A role for Bid in eosinophil apoptosis and in allergic airway reaction.
AB  - Bid, a proapoptotic member of Bcl-2 family, is involved in Fas receptor
      signaling. Fas activation promotes human eosinophil cell death and is believed to
      accelerate the resolution of pulmonary Th2-driven allergic reaction in mice. We
      hypothesized that Bid would regulate eosinophil apoptosis and Ag-induced airway
      inflammation, particularly eosinophilia. C57BL/6 Bid(-/-) and wild-type mice were
      immunized and repeatedly challenged with OVA, and bronchoalveolar lavage (BAL)
      fluid, lung, and spleen were collected 4-240 h after the final challenge.
      Cultured BAL eosinophils from Bid-deficient mice showed resistance to Fas
      mediated apoptotic DNA fragmentation, phosphatidylserine exposure, mitochondria
      depolarization, and caspase-3 activity. In addition, OVA-challenged Bid(-/-) mice
      had higher BAL eosinophilia and a lower proportion of BAL apoptotic eosinophils
      than Bid(+/+) mice. This was accompanied by augmented BAL levels of the
      eosinophilotactic cytokine, IL-5, and of the eosinophil-associated mediators, TGF
      beta1 and fibronectin. Finally, cultured OVA-stimulated lung mononuclear cells
      and splenocytes from Bid-deficient mice showed increased release of the Th2-type
      cytokines, IL-4 and IL-5, but no change in cell number. We conclude that Bid
      modulates BAL eosinophilia by regulating both eosinophil apoptosis and Th2-type
      cytokine production.

PMID- 19380822
TI  - IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells.
AB  - IL-27 is secreted by APCs in response to inflammatory stimuli and exerts a
      proinflammatory Th1-enhancing activity but also has significant anti-inflammatory
      functions. We examined the molecular mechanism by which IL-27 regulates TGFbeta
      plus IL-6- or IL-23-dependent Th17 development in the mouse and human systems. IL
      27 inhibited the production of IL-17A and IL-17F in naive T cells by suppressing,
      in a STAT1-dependent manner, the expression of the Th17-specific transcription
      factor RORgamma t. The in vivo significance of the role of IL-27 was addressed in
      delayed-type hypersensitivity response and experimental autoimmune
      encephalomyelitis (EAE). By generating mice deficient for the p28 subunit of IL
      27, we showed that IL-27 regulated the severity of delayed-type hypersensitivity
      response and EAE through its effects on Th17 cells. Furthermore, up-regulation of
      IL-10 in the CNS, which usually occurs late after EAE onset and plays a role in
      the resolution of the disease, was notably absent in IL-27p28(-/-) mice. These
      results show that IL-27 acts as a negative regulator of the developing IL-17A
      response in vivo, suggesting a potential therapeutic role for IL-27 in autoimmune
      diseases.

PMID- 19380823
TI  - NF-kappa B p50 regulates C/EBP alpha expression and inflammatory cytokine-induced
      neutrophil production.
AB  - NF-kappaB is a key transcriptional inducer of the inflammatory response in mature
      myeloid cells, and also stimulates cell survival, but its role in immature
      myeloid cell development has not been well characterized. C/EBPalpha is required
      for the development of monocytic and granulocytic myeloid cells from early
      progenitors, and NF-kappaB and C/EBPbeta cooperatively induce several
      inflammatory mediators. Having found that C/EBPalpha binds NF-kappaB p50
      preferentially compared with NF-kappaB p65, we have now investigated myelopoiesis
      in nfkb1(-/-) mice lacking NF-kappaB p50. Absence of p50 leads to a significant
      reduction in the number of granulocytic progenitors, CFU-granulocyte, obtained
      with G-CSF or GM-CSF in vitro and reduces neutrophil production in vivo in
      response to G-CSF, with preservation of monopoiesis in vitro in response to
      cytokines or LPS. To gain insight into the mechanism underlying reduced
      granulopoiesis in the absence of NF-kappaB p50, we assessed the expression of
      several myeloid regulatory proteins in lineage-negative, immature myeloid cells.
      Although PU.1, C/EBPbeta, and STAT3 levels were unchanged, C/EBPalpha protein and
      RNA levels were reduced approximately 3-fold in the absence of NF-kappaB p50. In
      addition, NF-kappaB p50 and C/EBPalpha bound the endogenous C/EBPalpha promoter
      in a chromatin immunoprecipitation assay, and NF-kappaB p50 trans activated the
      C/EBPalpha promoter, alone or in cooperation with C/EBPalpha. Despite reduction
      of C/EBPalpha, G-CSFR and M-CSFR levels were maintained in total marrow and in
      lineage-negative cells. Together, these data indicate that acute inflammation not
      only activates mature myeloid cells, but also stimulates neutrophil production
      via NF-kappaB p50 induction of C/EBPalpha transcription.

PMID- 19380824
TI  - Differential regulation of Foxp3 and IL-17 expression in CD4 T helper cells by
      IRAK-1.
AB  - Host immune responses are finely regulated by the opposing effects of Th17 and T
      regulatory (Treg) cells. Treg cells help to dampen inflammatory processes and
      Th17 cells facilitate various aspects of immune activation. The differentiation
      of Th cells depends on a unique combination of stimulants and subsequent
      activation of diverse transcription factors. In particular, cooperative
      activation of NFAT and Smad3 leads to the induction of Treg cells, and
      cooperation among STAT3 and Smad3 switches to the induction of Th17 cells. We
      have previously shown that the IL-1 receptor associated kinase 1 (IRAK-1)
      selectively activates STAT3 and inactivates NFAT. Physiological studies have
      shown that IRAK-1(-/-) mice are protected from developing various inflammatory
      diseases, including experimental autoimmune encephalomyelitis and atherosclerosis
      with unknown mechanism. In this study, we demonstrate that IRAK-1 plays a
      critical modulatory role in the differentiation of Th17 and Treg cells. Following
      stimulation with TCR agonists and TGFbeta, IRAK-1(-/-) CD4 Th cells display
      elevated nuclear NFATc2 levels and increased interaction of NFATc2 and Smad3,
      resulting in increased expression of Foxp3, a key marker for Treg cells. IRAK-1(
      /-) mice have constitutively higher populations of Treg cells. In contrast, when
      stimulated with TCR agonists together with IL-6 and TGF-beta, IRAK-1(-/-) CD4 Th
      cells exhibit attenuated STAT3 Ser727 phosphorylation and reduced expression of
      IL-17 and RORgamma t compared with wild-type cells. Correspondingly, IRAK-1
      deletion results in decreased IL-17 expression and dampened inflammatory
      responses in acute and chronic inflammatory mice models. Our data provides
      mechanistic explanation for the anti-inflammatory phenotypes of IRAK-1(-/-) mice.

PMID- 19380825
TI  - Alpha 2-macroglobulin capture allows detection of mast cell chymase in serum and
      creates a reservoir of angiotensin II-generating activity.
AB  - Human chymase is a highly efficient angiotensin II-generating serine peptidase
      expressed by mast cells. When secreted from degranulating cells, it can interact
      with a variety of circulating antipeptidases, but is mostly captured by alpha(2)
      macroglobulin, which sequesters peptidases in a cage-like structure that
      precludes interactions with large protein substrates and inhibitors, like
      serpins. The present work shows that alpha(2)-macroglobulin-bound chymase remains
      accessible to small substrates, including angiotensin I, with activity in serum
      that is stable with prolonged incubation. We used alpha(2)-macroglobulin capture
      to develop a sensitive, microtiter plate-based assay for serum chymase, assisted
      by a novel substrate synthesized based on results of combinatorial screening of
      peptide substrates. The substrate has low background hydrolysis in serum and is
      chymase-selective, with minimal cleavage by the chymotryptic peptidases cathepsin
      G and chymotrypsin. The assay detects activity in chymase-spiked serum with a
      threshold of approximately 1 pM (30 pg/ml), and reveals native chymase activity
      in serum of most subjects with systemic mastocytosis. alpha(2)-Macroglobulin
      bound chymase generates angiotensin II in chymase-spiked serum, and it appears in
      native serum as chymostatin-inhibited activity, which can exceed activity of
      captopril-sensitive angiotensin-converting enzyme. These findings suggest that
      chymase bound to alpha(2)-macroglobulin is active, that the complex is an
      angiotensin-converting enzyme inhibitor-resistant reservoir of angiotensin II
      generating activity, and that alpha(2)-macroglobulin capture may be exploited in
      assessing systemic release of secreted peptidases.

PMID- 19380826
TI  - Amyloid beta interaction with receptor for advanced glycation end products up
      regulates brain endothelial CCR5 expression and promotes T cells crossing the
      blood-brain barrier.
AB  - How circulating T cells infiltrate into the brain in Alzheimer disease (AD)
      remains unclear. We previously reported that amyloid beta (Abeta)-dependent CCR5
      expression in brain endothelial cells is involved in T cell transendothelial
      migration. In this study, we explored the signaling pathway of CCR5 up-regulation
      by Abeta. We showed that inhibitors of JNK, ERK, and PI3K significantly decreased
      Abeta-induced CCR5 expression in human brain microvascular endothelial cells
      (HBMECs). Chromatin immunoprecipitation assay revealed that Abeta-activated JNK,
      ERK, and PI3K promoted brain endothelial CCR5 expression via transcription factor
      Egr-1. Furthermore, neutralization Ab of receptor for advanced glycation end
      products (RAGE; an Abeta receptor) effectively blocked Abeta-induced JNK, ERK,
      and PI3K activation, contributing to CCR5 expression in HBMECs. Abeta fails to
      induce CCR5 expression when truncated RAGE was overexpressed in HBMECs.
      Transendothelial migration assay showed that the migration of MIP-1alpha (a CCR5
      ligand)-expressing AD patients' T cells through in vitro blood-brain barrier
      model was effectively blocked by anti-RAGE Ab, overexpression of truncated RAGE,
      and dominant-negative PI3K, JNK/ERK, or Egr-1 RNA interference in HBMECs,
      respectively. Importantly, blockage of intracerebral RAGE abolished the up
      regulation of CCR5 on brain endothelial cells and the increased T cell
      infiltration in the brain induced by Abeta injection in rat hippocampus. Our
      results suggest that intracerebral Abeta interaction with RAGE at BBB up
      regulates endothelial CCR5 expression and causes circulating T cell infiltration
      in the brain in AD. This study may provide a new insight into the understanding
      of inflammation in the progress of AD.

PMID- 19380827
TI  - Inflammation recapitulates the ontogeny of lymphoid stromal cells.
AB  - Stromal cells in lymphoid tissues regulate lymphocyte recruitment and survival
      through the expression of specific chemokines and cytokines. During inflammation,
      the same signals recruit lymphocytes to the site of injury; however, the
      "lymphoid" stromal (LS) cells producing these signals remain poorly
      characterized. We find that mouse inflammatory lesions and tumors develop gp38(+)
      LS cells, in recapitulation of the development of LS cells early during the
      ontogeny of lymphoid organs and the intestine, and express a set of genes that
      promotes the development of lymphocyte-permissive tissues. These gp38(+) LS cells
      are induced by a robust pathway that requires myeloid cells but not known Toll-
      or NOD-like receptors, the inflammasome, or adaptive immunity. Parabiosis and
      inducible genetic cell fate mapping experiments indicate that local precursors,
      presumably resident fibroblasts rather that circulating precursors, massively
      proliferate and give rise to LS cells during inflammation. Our results show that
      LS cells are both programmed during ontogeny and reinduced during inflammation.

PMID- 19380828
TI  - HMGB1 is phosphorylated by classical protein kinase C and is secreted by a
      calcium-dependent mechanism.
AB  - High-mobility group box 1 protein (HMGB1) has been studied as a key mediator of
      inflammatory diseases, including sepsis. Regulating secretion is important in the
      control of HMGB1-mediated inflammation. Previously, it was shown that HMGB1 needs
      to be phosphorylated for secretion. In this study, we show that HMGB1 is
      phosphorylated by the classical protein kinase C (cPKC) and is secreted by a
      calcium-dependent mechanism. For this study, RAW264.7 cells and human peripheral
      blood monocytes were treated with PI3K inhibitors wortmannin, LY294002, and
      ZSTK474, resulting in inhibition of LPS-stimulated HMGB1 secretion, whereas
      inhibitors of NF-kappaB and MAPKs p38 and ERK showed no inhibition. Akt inhibitor
      IV and mammalian target of rapamycin inhibitor rapamycin did not inhibit HMGB1
      secretion. However, the PKC inhibitors Go6983 (broad-spectrum PKC), Go6976
      (cPKC), and Ro-31-7549 (cPKC) and phosphoinositide-dependent kinase 1 inhibitor,
      which results in protein kinase C (PKC) inhibition, inhibited LPS-stimulated
      HMGB1 secretion. PKC activators, PMA and bryostatin-1, enhanced HMGB1 secretion.
      In an in vitro kinase assay, HMGB1 was phosphorylated by recombinant cPKC and by
      purified nuclear cPKC from LPS-stimulated RAW264.7 cells, but not by casein
      kinase II or cdc2. HMGB1 secretion was also induced by the calcium ionophore
      A23187 and inhibited by the Ca(2+) chelators BAPTA-AM and EGTA. These findings
      support a role for Ca(2+)-dependent PKC in HMGB1 secretion. Thus, we propose that
      cPKC is an effector kinase of HMGB1 phosphorylation in LPS-stimulated monocytes
      and PI3K-phosphoinositide-dependent kinase 1 may act in concert to control HMGB1
      secretion independent of the NF-kappaB, p38, and ERK pathways.

PMID- 19380829
TI  - An atypical protein kinase C (PKC zeta) plays a critical role in
      lipopolysaccharide-activated NF-kappa B in human peripheral blood monocytes and
      macrophages.
AB  - We have reported that the bacterial LPS induces the activation of NF-kappaB and
      inflammatory cytokine gene expression and that this requires the activity of
      small GTPase, RhoA. In this study, we show that an atypical protein kinase C
      isozyme, PKCzeta, associates functionally with RhoA and that PKCzeta acts as a
      signaling component downstream of RhoA. Stimulation of monocytes and macrophages
      with LPS resulted in PKCzeta activation and that inhibition of PKCzeta activity
      blocks both LPS-stimulated activation of NF-kappaB and IL-1beta gene expression.
      Our results also indicate that transforming growth factor beta-activated kinase 1
      acts as a signaling component downstream of PKCzeta in cytokine gene
      transcription stimulated by LPS in human peripheral blood monocytes and
      macrophages. The specificity of this response suggests an important role for the
      Rho GTPase/PKCzeta/transforming growth factor beta-activated kinase 1/NF-kappaB
      pathway in host defense and in proinflammatory cytokine synthesis induced by
      bacterial LPS.

PMID- 19380830
TI  - Deletion of PPAR gamma in alveolar macrophages is associated with a Th-1
      pulmonary inflammatory response.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is constitutively
      expressed at high levels in healthy alveolar macrophages, in contrast to other
      tissue macrophages and blood monocytes. PPARgamma ligands have been shown to down
      regulate IFN-gamma-stimulated inducible NO synthase (iNOS) in macrophages.
      Because NO is an important inflammatory mediator in the lung, we hypothesized
      that deletion of alveolar macrophage PPARgamma in vivo would result in up
      regulation of iNOS and other inflammatory mediators. The loss of PPARgamma in
      macrophages was achieved by crossing floxed (+/+) PPARgamma mice and a transgenic
      mouse containing the CRE recombinase gene under the control of the murine M
      lysozyme promoter (PPARgammaKO). Alveolar macrophages were harvested by
      bronchoalveolar lavage (BAL). Lymphocytes (CD8:CD4 ratio = 2.8) were increased in
      BAL of PPARgammaKO vs wild-type C57BL6; p < or = 0.0001. Both iNOS and IFN-gamma
      expression were significantly elevated (p < or = 0.05) in BAL cells. Th-1
      associated cytokines including IL-12 (p40), MIP-1alpha (CCL3), and IFN inducible
      protein-10 (IP-10, CXCL10) were also elevated. IL-4 and IL-17A were not detected.
      To test whether these alterations were due to the lack of PPARgamma, PPARgamma KO
      mice were intratracheally inoculated with a PPARgamma lentivirus construct.
      PPARgamma transduction resulted in significantly decreased iNOS and IFN-gamma
      mRNA expression, as well as reduced BAL lymphocytes. These results suggest that
      lack of PPARgamma in alveolar macrophages disrupts lung homeostasis and results
      in a Th1-like inflammatory response.

PMID- 19380831
TI  - The major outer membrane protein of a periodontopathogen induces IFN-beta and IFN
      stimulated genes in monocytes via lipid raft and TANK-binding kinase 1/IFN
      regulatory factor-3.
AB  - Surface molecules of pathogens play an important role in stimulating host immune
      responses. Elucidation of the signaling pathways activated by critical surface
      molecules in host cells provides insight into the molecular pathogenesis
      resulting from bacteria-host interactions. MspTL is the most abundant outer
      membrane protein of Treponema lecithinolyticum, which is associated with
      periodontitis, and induces expression of a variety of proinflammatory factors.
      Although bacteria and bacterial components like LPS and flagellin are known to
      induce IFN-beta, induction by bacterial surface proteins has not been reported.
      In the present study, we investigated MspTL-mediated activation of signaling
      pathways stimulating up-regulation of IFN-beta and IFN-stimulated genes in a
      human monocytic cell line, THP-1 cells, and primary cultured human gingival
      fibroblasts. MspTL treatment of the cells induced IFN-beta and the IFN-stimulated
      genes IFN-gamma-inducible protein-10 (IP-10) and RANTES. A neutralizing anti-IFN
      beta Ab significantly reduced the expression of IP-10 and RANTES, as well as STAT
      1 activation, which was also induced by MspTL. Experiments using specific small
      interfering RNA showed that MspTL activated TANK-binding kinase 1 (TBK1), but not
      inducible IkappaB kinase (IKKi). MspTL also induced dimerization of IFN
      regulatory factor-3 (IRF-3) and translocation into the nucleus. The lipid rapid
      disrupting agents methyl-beta-cyclodextrin, nystatin, and filipin inhibited the
      MspTL internalization and cellular responses, demonstrating that lipid raft
      activation was a prerequisite for MspTL cellular signaling. Our results
      demonstrate that MspTL, the major outer protein of T. lecithinolyticum, induced
      IFN-beta expression and subsequent up-regulation of IP-10 and RANTES via TBK1/IRF
      3/STAT-1 signaling secondary to lipid raft activation.

PMID- 19380832
TI  - Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL
      23/IL-17 axis.
AB  - Topical application of imiquimod (IMQ), a TLR7/8 ligand and potent immune
      activator, can induce and exacerbate psoriasis, a chronic inflammatory skin
      disorder. Recently, a crucial role was proposed for the IL-23/IL-17 axis in
      psoriasis. We hypothesized that IMQ-induced dermatitis in mice can serve as a
      model for the analysis of pathogenic mechanisms in psoriasis-like dermatitis and
      assessed its IL-23/IL-17 axis dependency. Daily application of IMQ on mouse back
      skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These
      lesions showed increased epidermal proliferation, abnormal differentiation,
      epidermal accumulation of neutrophils in microabcesses, neoangiogenesis, and
      infiltrates consisting of CD4(+) T cells, CD11c(+) dendritic cells, and
      plasmacytoid dendritic cells. IMQ induced epidermal expression of IL-23, IL-17A,
      and IL-17F, as well as an increase in splenic Th17 cells. IMQ-induced dermatitis
      was partially dependent on the presence of T cells, whereas disease development
      was almost completely blocked in mice deficient for IL-23 or the IL-17 receptor,
      demonstrating a pivotal role of the IL-23/IL-17 axis. In conclusion, the sole
      application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely
      resembling human psoriasis, critically dependent on the IL-23/IL-17 axis. This
      rapid and convenient model allows further elucidation of pathogenic mechanisms
      and evaluation of new therapies in psoriasis.

PMID- 19380834
TI  - Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the
      mouse.
AB  - Systemic sclerosis (SSc) is a connective tissue disorder of great clinical
      heterogeneity. Its pathophysiology remains unclear. Our aim was to evaluate the
      relative roles of reactive oxygen species (ROS) and of the immune system using an
      original model of SSc. BALB/c and immunodeficient BALB/c SCID mice were injected
      s.c. with prooxidative agents (hydroxyl radicals, hypochlorous acid,
      peroxynitrites, superoxide anions), bleomycin, or PBS everyday for 6 wk. Skin and
      lung fibrosis were assessed by histological and biochemical methods.
      Autoantibodies were detected by ELISA. The effects of mouse sera on H(2)O(2)
      production by endothelial cells and on fibroblast proliferation, and serum
      concentrations in advanced oxidation protein products (AOPP) were compared with
      sera from patients with limited or diffuse SSc. We observed that s.c.
      peroxynitrites induced skin fibrosis and serum anti-CENP-B Abs that characterize
      limited SSc, whereas hypochlorite or hydroxyl radicals induced cutaneous and lung
      fibrosis and anti-DNA topoisomerase 1 autoantibodies that characterize human
      diffuse SSc. Sera from hypochlorite- or hydroxyl radical-treated mice and of
      patients with diffuse SSc contained high levels of AOPP that triggered
      endothelial production of H(2)O(2) and fibroblast hyperproliferation. Oxidized
      topoisomerase 1 recapitulated the effects of whole serum AOPP. SCID mice
      developed an attenuated form of SSc, demonstrating the synergistic role of the
      immune system with AOPP in disease propagation. We demonstrate a direct role for
      ROS in SSc and show that the nature of the ROS dictates the form of SSc.
      Moreover, this demonstration is the first that shows the specific oxidation of an
      autoantigen directly participates in the pathogenesis of an autoimmune disease.

PMID- 19380833
TI  - Luteinizing hormone-releasing hormone enhances T cell recovery following
      allogeneic bone marrow transplantation.
AB  - Posttransplant immunodeficiency, specifically a lack of T cell reconstitution, is
      a major complication of allogeneic bone marrow transplantation. This
      immunosuppression results in an increase in morbidity and mortality from
      infections and very likely contributes to relapse. In this study, we demonstrate
      that sex steroid ablation using leuprolide acetate, a luteinizing hormone
      releasing hormone agonist (LHRHa), increases the number of lymphoid and myeloid
      progenitor cells in the bone marrow and developing thymocytes in the thymus.
      Although few differences are observed in the peripheral myeloid compartments, the
      enhanced thymic reconstitution following LHRHa treatment and allogeneic bone
      marrow transplantation leads to enhanced peripheral T cell recovery,
      predominantly in the naive T cell compartment. This results in an increase in T
      cell function in vivo and in vitro. Graft-versus-host-disease is not exacerbated
      by LHRHa treatment and graft-versus-tumor activity is maintained. Because LHRHa
      allows for reversible (and temporary) sex steroid ablation, has a strong safety
      profile, and has been clinically approved for diseases such as prostate and
      breast cancer, this drug treatment represents a novel therapeutic approach to
      reversal of thymic atrophy and enhancement of immunity following
      immunosuppression.

PMID- 19380835
TI  - Matrix metalloproteinase-1 is regulated in tuberculosis by a p38 MAPK-dependent,
      p-aminosalicylic acid-sensitive signaling cascade.
AB  - Mycobacterium tuberculosis (M. tb) must cause lung disease to spread. Matrix
      metalloproteinases (MMPs) degrade the extracellular matrix and are implicated in
      tuberculosis-driven tissue destruction. We investigated signaling pathways
      regulating macrophage MMP-1 and -7 in human pulmonary tuberculosis and examine
      the hypothesis that the antimycobacterial drug p-aminosalicylic acid acts by
      inhibiting such pathways. In primary human macrophages, M. tb up-regulates gene
      expression and secretion of MMP-1 (interstitial collagenase) and MMP-7
      (matrilysin). In tuberculosis patients, immunohistochemical analysis of lung
      biopsies demonstrates that p38 MAPK is phosphorylated in macrophages surrounding
      granulomas. In vitro, M. tb drives p38 phosphorylation. p38 inhibition suppresses
      M. tb-dependent MMP-1 secretion by 57.8% and concurrently increases secretion of
      its specific inhibitor TIMP-1 by 243.7%, demonstrating that p38 activity
      regulates matrix degradation by macrophages. p38 signals downstream to the
      cyclooxygenase 2/PGE(2) pathway. p-Aminosalicyclic acid, an agent used to treat
      drug-resistant tuberculosis, inhibits M. tb-driven MMP-1 but not MMP-7 gene
      expression and secretion. PAS acts by blocking PGE(2) production without
      affecting M. tb growth. In summary, p-aminosalicyclic acid decreases MMP-1
      activity by inhibiting a p38 MAPK-PG signaling cascade, suggesting that this
      pathway is a therapeutic target to reduce inflammatory tissue destruction in
      tuberculosis.

PMID- 19380836
TI  - Tumor regression following DNA vaccination and regulatory T cell depletion in neu
      transgenic mice leads to an increased risk for autoimmunity.
AB  - Modulation of the immune system to amplify anti-tumor immunity carries the risk
      of developing autoimmune diseases, including hypothyroidism, as seen with cancer
      patients undergoing clinical trials for immunotherapeutic regimens. Although
      there is a tendency to view autoimmunity as a positive indicator for cancer
      immunotherapy, some autoimmune manifestations can be life-threatening and
      necessitate prolonged medical intervention or removal from trial. We have
      established murine test models to assess such risks by monitoring,
      simultaneously, the immune reactivity to tumor-associated rat erbB-2 (neu) and
      another self Ag, mouse thyroglobulin (mTg). We previously reported that in wild
      type, thyroiditis-resistant BALB/c mice that underwent regression of neu(+) TUBO
      tumors following regulatory T cell (Treg) depletion, immune responses to rat neu
      and mTg with resultant autoimmune thyroiditis (EAT) were both enhanced. In this
      study, we tested the balance between tumor immunity and autoimmunity in neu
      transgenic BALB NeuT female mice. First, growth and progression of neu(+) tumor
      were compared in neu tolerant mice treated with either CD25 mAb to deplete Tregs
      and/or DNA vaccination. Only Treg depletion followed by neu DNA vaccination
      abrogated tolerance to neu, resulting in complete regression of neu(+) tumors, as
      well as long-term protection from spontaneous tumorigenesis in 58% of mice. The
      risk of developing EAT was then assessed by incorporated mTg immunization with or
      without LPS as adjuvant. In mice with induced tumor regression, mTg response was
      enhanced with modest increases in EAT development. Therefore, tumor regression
      induced by Treg depletion and DNA vaccination can exacerbate autoimmunity, which
      warrants close monitoring during immunotherapy.

PMID- 19380837
TI  - Glycemic control in type 2 diabetes: time for an evidence-based about-face?
AB  - Some diabetes guidelines set low glycemic control goals for patients with type 2
      diabetes mellitus (such as a hemoglobin A(1c) level as low as 6.5% to 7.0%) to
      avoid or delay complications. Our review and critique of recent large randomized
      trials in patients with type 2 diabetes suggest that tight glycemic control
      burdens patients with complex treatment programs, hypoglycemia, weight gain, and
      costs and offers uncertain benefits in return. We believe clinicians should
      prioritize supporting well-being and healthy lifestyles, preventive care, and
      cardiovascular risk reduction in these patients. Glycemic control efforts should
      individualize hemoglobin A(1c) targets so that those targets and the actions
      necessary to achieve them reflect patients' personal and clinical context and
      their informed values and preferences.

PMID- 19380838
TI  - Regulatory forum.

PMID- 19380839
TI  - Discovery of metabolomics biomarkers for early detection of nephrotoxicity.
AB  - Drug-induced nephrotoxicity is a major concern, since many pharmacological
      compounds are filtered through the kidneys for excretion into urine. To discover
      biochemical biomarkers useful for early identification of nephrotoxicity,
      metabolomic experiments were performed on Sprague-Dawley Crl:CD (SD) rats treated
      with the nephrotoxins gentamicin, cisplatin, or tobramycin. Using a combination
      of gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass
      spectrometry (LC/MS), a global, nontargeted metabolomics analysis was performed
      on urine and kidney samples collected after one, five, and twenty-eight dosing
      days. Increases in polyamines and amino acids were observed in urine from drug
      treated rats after a single dose, and prior to observable histological kidney
      damage and conventional clinical chemistry indications of nephrotoxicity. Thus,
      these metabolites are potential biomarkers for the early detection of drug
      induced nephrotoxicity. Upon prolonged dosing, nephrotoxin-induced changes
      included a progressive loss of amino acids in urine, concomitant with a decrease
      in amino acids and nucleosides in kidney tissue. A nephrotoxicity prediction
      model, based on the levels of branched-chain amino acids in urine, distinguished
      nephrotoxin-treated samples from vehicle-control samples, with 100%, 93%, and 70%
      accuracy at day 28, day 5, and day 1, respectively. Thus, this panel of
      biomarkers may provide a noninvasive method to detect kidney injury long before
      the onset of histopathological kidney damage.

PMID- 19380841
TI  - Eosinophilic inclusions in rat Clara cells and the effect of an inhaled
      corticosteroid.
AB  - Large eosinophilic cytoplasmic inclusions (ECIs) are occasionally seen in
      untreated rat Clara cells. Following inhalation exposure to a corticosteroid, the
      number of ECIs was increased. This is the first histopathological description of
      rat ECIs and attempted characterization by immunohistochemistry, in situ
      hybridization, and electron microscopy. ECIs were strongly positive for
      surfactant protein D (SP-D) and weakly positive for Clara cell specific protein
      (CCSP). Clara cell cytoplasm was positive for CCSP mRNA regardless of ECIs, but
      not within ECIs. Corticosteroid treatment and ECI presence did not affect the
      immunohistochemistry and in situ hybridization staining intensities. Electron
      microscopy revealed large intracytoplasmic granules with an irregular limiting
      membrane. The ECI number was microscopically quantified in rats from three-, six
      , and twenty-four-month studies. The mean ECI counts in treated rats increased
      from three- to fifty-four-fold with a positive dose-related trend, when compared
      with vehicle controls. Although the mechanism is unclear, SP-D and to a lesser
      extent CCSP accumulate in the ECIs. As human bronchial epithelium does not appear
      to contain structures analogous to the ECI, it is suggested that the observation
      of an increased number of ECIs in the treated rats is not likely to be relevant
      for human clinical risk assessment.

PMID- 19380840
TI  - Strain-related differences in urine composition of male rats of potential
      relevance to urolithiasis.
AB  - In carcinogenicity studies with PPAR gamma and alpha/gamma agonists, urinary
      bladder tumors have been reported in Harlan Sprague-Dawley (HSD) and Charles
      River Sprague-Dawley (SD) but not Wistar (WI) rats, with urolithiasis purported
      to be the inciting event. In two 3-month studies, the authors investigated strain
      related differences in urine composition by sampling urine multiple times daily.
      Urine pH, electrolytes, creatinine, protein, citrate and oxalate levels, and
      serum citrate were assessed; urine sediment was analyzed by scanning electron
      microscopy and energy dispersive x-ray spectroscopy. HSD rats had significantly
      higher urine calcium than SD or WI rats, primarily as calcium phosphate
      containing precipitate. When compared to SD rats, HSD rats had lower urine
      volume, higher urine protein, and a comparable (week 4) to lower (week 13) burden
      of MgNH(4)PO(4) aggregates. Relative to WI rats, HSD rats had higher urine
      protein and magnesium and lower serum and urine citrate. Overall, the
      susceptibility to urolithiasis in male rats was HSD > SD > WI; this was likely
      due to strain-related differences in the amount of urine protein (a nidus for
      crystal formation), lithogenic ions, citrate (an inhibitor of lithogenesis),
      and/or volume. Strain-related differences in urine composition need to be
      considered when interpreting the outcome of studies with compounds that alter
      urine composition.

PMID- 19380842
TI  - Effects of chronic exposure to crack cocaine on the respiratory tract of mice.
AB  - Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory
      tract, including asthma exacerbations, lung edema and hemorrhage, and nasal
      mucosal alterations. Few studies, however, have assessed respiratory tract
      pathology in habitual users of crack cocaine. Here, we describe the histological
      alterations in the respiratory tract of mice caused by chronic inhalation of
      crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g
      crack cocaine in an inhalation chamber once a day for two months and compared to
      controls (n = 10). We then morphometrically analyzed nose and bronchiolar
      epithelial alterations, bronchiolar and alveolar macrophage cell density,
      alveolar hemosiderin content, and in addition determined the vasoconstriction
      index and the wall thickness of pulmonary arteries. The serum cocaine level was
      212.5 ng/mL after a single inhalation. The mucus content of the nasal epithelium
      increased in crack-exposed animals, and the nasal and bronchial epithelium
      thickness decreased significantly. The alveolar hemosiderin content and the
      alveolar and bronchiolar macrophage cell density increased in animals exposed to
      crack. The vasoconstriction index increased in the pulmonary arteries of the
      exposed group. Chronic crack cocaine inhalation causes extensive histological
      changes along the entire respiratory tract.

PMID- 19380843
TI  - Spontaneous ganglioneuroma possibly originating from the trigeminal ganglion in a
      B6C3F1 mouse.
AB  - In a carcinogenicity study, a neuronal tumor in the cranial cavity was observed
      in a 110-week-old female B6C3F1 mouse. At necropsy, the tumor was seen at the
      site of the pituitary gland. Histologically, the tumor consisted of well
      differentiated ganglion cells, nerve fiber/neuropil-like elements and ganglion
      like cells. The tumor was composed mainly of ganglion-like cells, which were
      arranged in solid sheets interspersed with thin fibrovascular stroma. Nissl
      substance was detected at the margin in the cytoplasm of well-differentiated
      ganglion cells, and nerve fibers were identified by the Kluever-Barrera method.
      Immunohistochemically, the well-differentiated ganglion cells were positive for S
      100, neurofilament protein (NF), neuron-specific enolase (NSE), synaptophysin,
      and chromogranin A. The nerve fiber/neuropil-like elements were positive for S
      100, NF, NSE, and glial fibrillary acidic protein (GFAP), and the ganglion-like
      cells were strongly positive only for NSE and synaptophysin. On the other hand,
      there were no pituitary cells, such as prolactin-positive or adrenocorticotropic
      hormone (ACTH)-positive cells in the tumor tissue. Detailed histopathological
      examination suggested that the tumor might be a ganglioneuroma arising from the
      trigeminal ganglion. This report provides additional histopathological evidence
      of peripheral nerve neoplasms in mice.

PMID- 19380844
TI  - Canine cardiac rhabdomyoma.
AB  - A well-circumscribed, expansile, and nonencapsulated cardiac rhabdomyoma composed
      of tightly arranged, large, variably sized, ovoid to irregular, swollen myocytes
      with deeply eosinophilic cytoplasm and varying degrees of cytoplasmic vacuolation
      was detected in an eight- to nine-month-old female beagle dog in a routine
      toxicology study. By histochemistry, the neoplasm was periodic acid-Schiff
      positive. By immunohistochemistry (IHC), neoplastic cells were positive for
      desmin and myoglobin and negative for vimentin and smooth muscle actin.
      Spontaneous lesions in the heart of young beagle dogs are rare in drug safety
      studies. On the basis of histopathology, histochemistry, and IHC findings, a
      diagnosis of cardiac rhabdomyoma was made. Cardiac rhabdomyoma is one of the most
      frequently occurring primary tumors of the heart and, by far, the most common
      neoplasm in human infants and children. To our knowledge, this is the first
      report of the canine cardiac rhabdomyoma.

PMID- 19380845
TI  - Apparent alveolar bronchiolar tumors arising in the mediastinum of F344 rats.
AB  - Rare tumors were observed in chronic studies in F-344 rats that were purely or
      largely free in the mediastinal cavity, yet had the histological architecture of
      alveolar bronchiolar tumors. They had originally been diagnosed as either
      pulmonary alveolar bronchiolar tumors, mediastinal mesotheliomas, or thymomas.
      The authors described these tumors, estimated the fraction of thoracic tumors
      that they represented, and carried out a preliminary immunohistochemical
      investigation of whether they were of pulmonary or mesothelial origin. Sections
      of 715 thoracic tumors originally diagnosed as alveolar bronchiolar tumors,
      mesotheliomas, or thymomas from control or treated F-344 rats in NTP two-year
      studies were reviewed. Thirty (4%) were found to be purely or largely
      mediastinal, yet to have an alveolar bronchiolar histological pattern. A subset
      of these tumors and some typical intrapulmonary alveolar bronchiolar carcinomas
      and pleural mesotheliomas were immunostained for Clara cell secretory protein
      (CCSP), beta-tubulin IV, and Wilm's tumor 1 susceptibility gene products (WT1).
      The tumors with the histological architecture of alveolar bronchiolar tumors
      immunostained positive for CCSP and negative for WT1, implying they might have
      been of alveolar bronchiolar origin, despite their predominantly mediastinal
      location, although more certain identification would require the use of a larger
      panel of antibodies.

PMID- 19380846
TI  - The ACVP/STP coalition responds to the continued shortage of veterinary
      pathologists.

PMID- 19380847
TI  - Regulatory Affairs introduction.

PMID- 19380848
TI  - Summaries for patients. Control of cardiovascular disease and diabetes in the
      United States: trends in disparities and effects of Medicare coverage.

PMID- 19380849
TI  - Summaries for patients. Re-treating patients with chronic hepatitis C who have
      not responded to peginterferon-alpha2b.

PMID- 19380850
TI  - Summaries for patients. Using genetic and other factors to predict risk for type
      2 diabetes.

PMID- 19380851
TI  - Summaries for patients. Preventing tobacco use and related diseases in adults and
      pregnant women: U.S. Preventive Services Task Force reaffirmation recommendation
      statement.

PMID- 19380852
TI  - Differences in control of cardiovascular disease and diabetes by race, ethnicity,
      and education: U.S. trends from 1999 to 2006 and effects of medicare coverage.
AB  - BACKGROUND: Efforts to improve the care of cardiovascular disease and diabetes or
      expand insurance coverage for adults with these conditions may reduce differences
      in clinical outcomes. OBJECTIVE: To assess recent national trends in disease
      control, trends in sociodemographic differences in control, and changes in
      sociodemographic differences after age 65 years associated with near-universal
      Medicare coverage. DESIGN: Observational and quasi-experimental analyses of
      repeated cross-sectional data. SETTING: National Health and Nutrition Examination
      Survey, 1999 to 2006. PARTICIPANTS: Adults age 40 to 85 years with relevant
      clinical conditions. MEASUREMENTS: Blood pressure control (<140/90 mm Hg) and
      mean systolic blood pressure among adults with hypertension (n = 4521); glycemic
      control (hemoglobin A(1c) levels <7.0%) and mean hemoglobin A(1c) levels among
      those with diabetes (n = 1733); and total cholesterol level control (<5.2 mmol/L
      [<200 mg/dL]) and mean total cholesterol levels among those with coronary heart
      disease, stroke, or diabetes (n = 2928). Temporal trends in these measures were
      compared by race, ethnicity, and education, and sociodemographic differences were
      compared above and below eligibility for Medicare at age 65 years. RESULTS:
      Disease control improved significantly between 1999 and 2006 for all 6 measures
      (P < 0.001). These trends did not differ by race or ethnicity or by education (P
      > or = 0.185 for group-time interactions), except that white-Hispanic differences
      in glycemic control widened (P = 0.042). Black-white differences in systolic
      blood pressure were smaller among adults age 65 to 85 years than among adults age
      40 to 64 years (reduction in difference, 4.2 mm Hg; P = 0.009). Black-white
      differences in hemoglobin A(1c) levels were also smaller after age 65 years
      (reduction in difference, 0.7%; P = 0.005), as were Hispanic-white differences
      (reduction in difference, 0.7%; P = 0.007) and differences between less and more
      educated adults (reduction in difference, 0.5%; P = 0.033). LIMITATION: Data were
      cross-sectional, and estimates may have been biased by coincidental events at age
      65 years, such as retirement, that may affect disease control. CONCLUSION:
      Control of blood pressure and glucose and cholesterol levels has improved since
      1999 for adults with cardiovascular disease and diabetes, but racial, ethnic, or
      socioeconomic differences have not narrowed significantly. Medicare coverage
      after age 65 years is associated with reductions in these differences. PRIMARY
      FUNDING SOURCE: The Commonwealth Fund.

PMID- 19380854
TI  - Joint effects of common genetic variants on the risk for type 2 diabetes in U.S.
      men and women of European ancestry.
AB  - BACKGROUND: Genome-wide association studies have identified novel type 2 diabetes
      loci, each of which has a modest impact on risk. OBJECTIVE: To examine the joint
      effects of several type 2 diabetes risk variants and their combination with
      conventional risk factors on type 2 diabetes risk in 2 prospective cohorts.
      DESIGN: Nested case-control study. SETTING: United States. PARTICIPANTS: 2809
      patients with type 2 diabetes and 3501 healthy control participants of European
      ancestry from the Health Professionals Follow-up Study and Nurses' Health Study.
      MEASUREMENTS: A genetic risk score (GRS) was calculated on the basis of 10
      polymorphisms in 9 loci. RESULTS: After adjustment for age and body mass index
      (BMI), the odds ratio for type 2 diabetes with each point of GRS, corresponding
      to 1 risk allele, was 1.19 (95% CI, 1.14 to 1.24) and 1.16 (CI, 1.12 to 1.20) for
      men and women, respectively. Persons with a BMI of 30 kg/m(2) or greater and a
      GRS in the highest quintile had an odds ratio of 14.06 (CI, 8.90 to 22.18)
      compared with persons with a BMI less than 25 kg/m(2) and a GRS in the lowest
      quintile after adjustment for age and sex. Persons with a positive family history
      of diabetes and a GRS in the highest quintile had an odds ratio of 9.20 (CI, 5.50
      to 15.40) compared with persons without a family history of diabetes and with a
      GRS in the lowest quintile. The addition of the GRS to a model of conventional
      risk factors improved discrimination by 1% (P < 0.001). LIMITATION: The study
      focused only on persons of European ancestry; whether GRS is associated with type
      2 diabetes in other ethnic groups remains unknown. CONCLUSION: Although its
      discriminatory value is currently limited, a GRS that combines information from
      multiple genetic variants might be useful for identifying subgroups with a
      particularly high risk for type 2 diabetes. PRIMARY FUNDING SOURCE: National
      Institutes of Health.

PMID- 19380853
TI  - Re-treatment of patients with chronic hepatitis C who do not respond to
      peginterferon-alpha2b: a randomized trial.
AB  - BACKGROUND: Many patients with chronic hepatitis C have not responded to therapy
      with pegylated interferon plus ribavirin. OBJECTIVE: To evaluate use of
      peginterferon-alpha2a plus ribavirin to re-treat nonresponders to peginterferon
      alpha2b plus ribavirin. DESIGN: Randomized, parallel-group trial conducted
      between September 2003 and February 2007. Patients and researchers were not
      blinded to intervention assignment. Random assignment was centralized, computer
      generated, and stratified by geographic region, hepatitis C virus (HCV) genotype,
      and histologic diagnosis. SETTING: 106 international centers. PATIENTS: 950
      nonresponders to 12 or more weeks of therapy with peginterferon-alpha2b plus
      ribavirin. INTERVENTION: Peginterferon-alpha2a, 360 microg/wk, for 12 weeks, then
      180 microg/wk to complete 72 weeks (group A) or 48 weeks (group B), or
      peginterferon-alpha2a, 180 microg/wk for 72 weeks (group C) or 48 weeks (group
      D). All patients received ribavirin, 1000 or 1200 mg/d. MEASUREMENTS: Sustained
      virologic response (SVR), defined as undetectable (<50 IU/mL) HCV RNA levels 24
      weeks after the end of treatment. RESULTS: The SVR rates in groups A (n = 317), B
      (n = 156), C (n = 156), and D (n = 313) were 16%, 7%, 14%, and 9%, respectively
      (relative risk [RR] for group A vs. group D [the primary comparison], 1.80 [95%
      CI, 1.17 to 2.77]; P = 0.006). Extended treatment duration increased SVR rates
      (16% for 72 weeks [groups A and C] vs. 8% for 48 weeks [groups B and D]; RR, 2.00
      [CI, 1.32 to 3.02]; P < 0.001). Complete viral suppression (HCV RNA level <50
      IU/mL)at week 12 was achieved in 21% of patients in groups A and B and 13% of
      those in groups C and D. Rates of SVR were 49% (77 of 157 patients) and 4% (32 of
      719 patients) among those with and without complete viral suppression at week 12,
      respectively. LIMITATION: Nonresponders to peginterferon-alpha2a plus ribavirin
      were not evaluated. CONCLUSION: Re-treating nonresponders to therapy with
      peginterferon-alpha2b plus ribavirin for 72 weeks significantly increases SVR
      rates compared with re-treating them for 48 weeks. The overall SVR rate was low,
      but patients who are most likely to respond to re-treatment can be identified at
      week 12. PRIMARY FUNDING SOURCE: Roche.

PMID- 19380855
TI  - Counseling and interventions to prevent tobacco use and tobacco-caused disease in
      adults and pregnant women: U.S. Preventive Services Task Force reaffirmation
      recommendation statement.
AB  - DESCRIPTION: Reaffirmation of the 2003 U.S. Preventive Services Task Force
      (USPSTF) recommendation on counseling to prevent tobacco use. METHODS: The USPSTF
      reviewed new evidence in the U.S. Public Health Service's 2008 clinical practice
      guideline and determined that the net benefits of tobacco cessation interventions
      in adults and pregnant women remain well established. RECOMMENDATIONS: Ask all
      adults about tobacco use and provide tobacco cessation interventions for those
      who use tobacco products. (Grade A recommendation) Ask all pregnant women about
      tobacco use and provide augmented, pregnancy-tailored counseling for those who
      smoke. (Grade A recommendation).

PMID- 19380856
TI  - Akhenaten and the strange physiques of Egypt's 18th dynasty.
AB  - Akhenaten was one of Egypt's most controversial pharaohs, in part because of his
      strange appearance in images produced after he had declared Aten, the Sun-disc,
      his one-and-only god. Whether these were symbolic representations or realistic
      ones that indicate a deforming genetic disorder is the subject of continuing
      debate. The authors present evidence that the bizarre physical features portrayed
      in these images are not only realistic but were shared by many members of Egypt's
      18th Dynasty. The features are best explained by either 2 different familial
      disorders-the aromatase excess syndrome and the sagittal craniosynostosis
      syndrome-or a variant of the Antley-Bixler syndrome caused by a novel mutation in
      one of the genes controlling the P450 enzymes, which regulate steroidogenesis and
      cranial bone formation.

PMID- 19380857
TI  - Universal health care as a health disparity intervention.

PMID- 19380858
TI  - Inshala.

PMID- 19380859
TI  - Composite outcomes can distort the nature and magnitude of treatment benefits in
      clinical trials.

PMID- 19380861
TI  - Screening strategies for hemochromatosis.

PMID- 19380862
TI  - Gallbladder carriage of Salmonella paratyphi A may be an important factor in the
      increasing incidence of this infection in South Asia.

PMID- 19380863
TI  - Isolation of Mycobacterium kyorinense in a patient with respiratory failure.

PMID- 19380864
TI  - Strongyloides hyperinfection: an unusual cause of respiratory failure.

PMID- 19380865
TI  - Cancer care: a microcosm of the problems facing all of health care.

PMID- 19380866
TI  - Differential efficacy of bortezomib plus chemotherapy within molecular subtypes
      of diffuse large B-cell lymphoma.
AB  - Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed
      distinct molecular subtypes that include germinal center B cell-like (GCB) and
      activated B cell-like (ABC) DLBCL. ABC DLBCL has a worse survival after upfront
      chemotherapy and is characterized by constitutive activation of the antiapoptotic
      nuclear factor-kappa B (NF-kappaB) pathway, which can inhibit chemotherapy. We
      hypothesized that inhibition of NF-kappaB might sensitize ABC but not GCB DLBCL
      to chemotherapy and improve outcome. As the proteasome inhibitor bortezomib can
      inhibit NF-kappaB through blocking IkappaBalpha degradation, we investigated
      bortezomib alone followed by bortezomib and doxorubicin-based chemotherapy in
      recurrent DLBCL. Tumor tissue was analyzed by gene expression profiling and/or
      immunohistochemistry to identify molecular DLBCL subtypes. As a control, we
      showed that relapsed/refractory ABC and GCB DLBCL have equally poor survivals
      after upfront chemotherapy. Bortezomib alone had no activity in DLBCL, but when
      combined with chemotherapy, it demonstrated a significantly higher response (83%
      vs 13%; P < .001) and median overall survival (10.8 vs 3.4 months; P = .003) in
      ABC compared with GCB DLBCL, respectively. These results suggest bortezomib
      enhances the activity of chemotherapy in ABC but not GCB DLBCL, and provide a
      rational therapeutic approach based on genetically distinct DLBCL subtypes. This
      trial is registered with http://www.ClinicalTrials.gov under identifier
      NCT00057902.

PMID- 19380867
TI  - Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme
      scavenging.
AB  - Haptoglobin, the haptoglobin-hemoglobin receptor CD163, and the heme oxygenase-1
      are proteins with a well-established function in the clearance and metabolism of
      "free" hemoglobin released during intravascular hemolysis. This scavenging system
      counteracts the potentially harmful oxidative and NO-scavenging effects
      associated with "free" hemoglobin, and, furthermore, elicits an anti-inflammatory
      response. In the late primate evolution, haptoglobin variants with distinct
      functions have arisen, including haptoglobin polymers and the haptoglobin-related
      protein. The latter associates with a subspecies of high-density lipoprotein
      (HDL) particles playing a crucial role in the innate immunity against certain
      trypanosome parasites. Recent studies have elucidated this fairly sophisticated
      immune defense mechanism that takes advantage of a trypanosomal haptoglobin
      hemoglobin receptor evolved to supply the parasite with heme. Because of the high
      resemblance between haptoglobin and haptoglobin-related protein, the receptor
      also takes up the complex of hemoglobin and the HDL-bound haptoglobin-related
      protein. This tricks the parasite into internalizing another HDL-associated
      protein and toxin, apolipoprotein L-I, that kills the parasite. In conclusion,
      variant human homologous hemoglobin-binding proteins that collectively may be
      designated the haptoglobins have diverted from the haptoglobin gene. On
      hemoglobin and receptor interaction, these haptoglobins contribute to different
      biologic events that go beyond simple removal from plasma of the toxic
      hemoglobin.

PMID- 19380869
TI  - CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein
      signaling.
AB  - The stromal cell-derived factor-1/CXCL12 chemokine engages the CXCR4 and CXCR7
      receptors and regulates homeostatic and pathologic processes, including
      organogenesis, leukocyte homeostasis, and tumorigenesis. Both receptors are
      widely expressed in mammalian cells, but how they cooperate to respond to CXCL12
      is not well understood. Here, we show that CXCR7 per se does not trigger
      G(alphai) protein-dependent signaling, although energy transfer assays indicate
      that it constitutively interacts with G(alphai) proteins and undergoes CXCL12
      mediated conformational changes. Moreover, when CXCR4 and CXCR7 are coexpressed,
      we show that receptor heterodimers form as efficiently as receptor homodimers,
      thus opening the possibility that CXCR4/CXCR7 heterodimer formation has
      consequences on CXCL12-mediated signals. Indeed, expression of CXCR7 induces
      conformational rearrangements within preassembled CXCR4/G(alphai) protein
      complexes and impairs CXCR4-promoted G(alphai)-protein activation and calcium
      responses. Varying CXCR7 expression levels and blocking CXCL12/CXCR7 interactions
      in primary T cells suggest that CXCR4/CXCR7 heterodimers form in primary
      lymphocytes and regulate CXCL12-promoted chemotaxis. Taken together, these
      results identify CXCR4/CXCR7 heterodimers as distinct functional units with novel
      properties, which can contribute to the functional plasticity of CXCL12.

PMID- 19380868
TI  - IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection.
AB  - Interleukin 7 (IL-7) is a common gamma chain receptor cytokine implicated in
      thymopoiesis and in peripheral expansion and survival of T lymphocytes. The
      safety and activity of recombinant human IL-7 (rhIL-7) administration were
      therefore examined in HIV-infected persons. In this prospective randomized
      placebo-controlled study, a single subcutaneous dose of rhIL-7 was well tolerated
      with biologic activity demonstrable at 3 microg/kg and a maximum tolerated dose
      of 30 microg/kg. Injection site reactions and transient elevations of liver
      function tests were the most notable side effects. Transient increases in plasma
      HIV-RNA levels were observed in 6 of 11 IL-7-treated patients. Recombinant hIL-7
      induced CD4 and CD8 T cells to enter cell cycle; cell-cycle entry was also
      confirmed in antigen-specific CD8 T cells. Administration of rhIL-7 led to
      transient down-regulation of the IL-7 receptor alpha chain (CD127) in both CD4(+)
      and CD8(+) T cells. Single-dose rhIL-7 increased the numbers of circulating
      CD4(+) and CD8(+) T cells, predominantly of central memory phenotype. The
      frequency of CD4(+) T cells with a regulatory T-cell phenotype (CD25(high)
      CD127(low)) did not change after rhIL-7 administration. Thus, rhIL-7 has a
      biologic and toxicity profile suggesting a potential for therapeutic trials in
      HIV infection and other settings of lymphopenia. This clinical trial has been
      registered at http://www.clinicaltrials.gov under NCT0099671.

PMID- 19380870
TI  - IL-15 produced and trans-presented by DCs underlies homeostatic competition
      between CD8 and {gamma}{delta} T cells in vivo.
AB  - Homeostatic mechanism by which peripheral T-cell subsets are maintained in vivo
      remains largely unknown. Using a T-cell proliferation model under lymphopenic
      settings, we now demonstrate that gammadelta T cells limit CD8 T-cell expansion
      but not the initial proliferation after transfer into lymphopenic recipients.
      Interleukin-15 (IL-15) produced by and trans-presented on the membrane of the
      CD11c(+) dendritic cells (DCs) is the key factor that mediates homeostatic
      competition between CD8 and gammadelta T cells, revealing previously unrecognized
      IL-15-dependent homeostatic mechanisms between different T-cell subsets in vivo.

PMID- 19380872
TI  - Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2
      macroglobulin in blood.
AB  - Hepcidin is a major regulator of iron metabolism. Hepcidin-based
      therapeutics/diagnostics could play roles in hematology in the future, and thus,
      hepcidin transport is crucial to understand. In this study, we identify alpha2
      macroglobulin (alpha2-M) as the specific hepcidin-binding molecule in blood.
      Interaction of 125I-hepcidin with alpha2-M was identified using fractionation of
      plasma proteins followed by native gradient polyacrylamide gel electrophoresis
      and mass spectrometry. Hepcidin binding to nonactivated alpha2-M displays high
      affinity (Kd 177 +/- 27 nM), whereas hepcidin binding to albumin was nonspecific
      and displayed nonsaturable kinetics. Surprisingly, the interaction of hepcidin
      with activated alpha2-M exhibited a classical sigmoidal binding curve
      demonstrating cooperative binding of 4 high-affinity (Kd 0.3 microM) hepcidin
      binding sites. This property probably enables efficient sequestration of hepcidin
      and its subsequent release or inactivation that may be important for its effector
      functions. Because alpha2-M rapidly targets ligands to cells via receptor
      mediated endocytosis, the binding of hepcidin to alpha2-M may influence its
      functions. In fact, the alpha2-M-hepcidin complex decreased ferroportin
      expression in J774 cells more effectively than hepcidin alone. The demonstration
      that alpha2-M is the hepcidin transporter could lead to better understanding of
      hepcidin physiology, methods for its sensitive measurement and the development of
      novel drugs for the treatment of iron-related diseases.

PMID- 19380871
TI  - Short-chain fatty acid-mediated effects on erythropoiesis in primary definitive
      erythroid cells.
AB  - Short-chain fatty acids (SCFAs; butyrate and propionate) up-regulate
      embryonic/fetal globin gene expression through unclear mechanisms. In a murine
      model of definitive erythropoiesis, SCFAs increased embryonic beta-type globin
      gene expression in primary erythroid fetal liver cells (eFLCs) after 72 hours in
      culture, from 1.7% (+/- 1.2%) of total beta-globin gene expression at day 0 to
      4.9% (+/- 2.2%) in propionate and 5.4% (+/- 3.4%) in butyrate; this effect was
      greater in butyrate plus insulin/erythropoietin (BIE), at 19.5% (+/- 8.3%)
      compared with 0.1% (+/- 0.1%) in ins/EPO alone (P < .05). Fetal gamma-globin gene
      expression was increased in human transgene-containing eFLCs, to 35.9% (+/- 7.0%)
      in BIE compared with 4.4% (+/- 4.2%) in ins/EPO only (P < .05). Embryonic globin
      gene expression was detectable in 11 of 15 single eFLCs treated with BIE, but in0
      of 15 ins/EPO-only treated cells. Butyrate-treated [65.5% (+/- 9.9%)] and 77.5%
      (+/- 4.0%) propionate-treated eFLCs were highly differentiated in culture,
      compared with 21.5% (+/- 3.5%) in ins/EPO (P < .005). Importantly, signaling
      intermediaries, previously implicated in induced embryonic/fetal globin gene
      expression (STAT5, p42/44, and p38), were not differentially activated by SCFAs
      in eFLCs; but increased bulk histone (H3) acetylation was seen in SCFA-treated
      eFLCs. SCFAs induce embryonic globin gene expression in eFLCS, which are a useful
      short-term and physiologic primary cell model of embryonic/fetal globin gene
      induction during definitive erythropoiesis.

PMID- 19380873
TI  - Peter Friedl: Painting a picture of cancer immunology. Interview by Caitlin
      Sedwick.

PMID- 19380874
TI  - New science - new ways to communicate it.

PMID- 19380875
TI  - The circuitry of cargo flux in the ESCRT pathway.
AB  - The endosomal sorting complex required for transport (ESCRT) complexes sort
      ubiquitinated membrane proteins into multivesicular bodies, which is a key step
      in the lysosomal degradation pathway. Shields et al. (Shields, S.B., A.J.
      Oestreich, S. Winistorfer, D. Nguyen, J.A. Payne, D.J. Katzmann, and R. Piper.
      2009. J. Cell Biol. 185:213-224) identify a new ubiquitin-binding site in ESCRT-I
      and provide evidence that the upstream ESCRT-I and -II complexes sort cargo in
      parallel rather than in series.

PMID- 19380876
TI  - Puma strikes Bax.
AB  - The commitment to programmed cell death via apoptosis is largely made upon
      activation of the proapoptotic mitochondrial proteins Bax or Bak. In this issue,
      Gallenne et al. (Gallenne, C., F. Gautier, L. Oliver, E. Hervouet, B. Noel, J.A.
      Hickman, O. Geneste, P.-F. Cartron, F.M. Vallette, S. Manon, and P. Juin. 2009.
      J. Cell Biol. 185:279-290) provide evidence that the p53 up-regulated modulator
      of apoptosis (Puma) protein can directly activate Bax.

PMID- 19380877
TI  - ESCRT ubiquitin-binding domains function cooperatively during MVB cargo sorting.
AB  - Ubiquitin (Ub) sorting receptors facilitate the targeting of ubiquitinated
      membrane proteins into multivesicular bodies (MVBs). Ub-binding domains (UBDs)
      have been described in several endosomal sorting complexes required for transport
      (ESCRT). Using available structural information, we have investigated the role of
      the multiple UBDs within ESCRTs during MVB cargo selection. We found a novel UBD
      within ESCRT-I and show that it contributes to MVB sorting in concert with the
      known UBDs within the ESCRT complexes. These experiments reveal an unexpected
      level of coordination among the ESCRT UBDs, suggesting that they collectively
      recognize a diverse set of cargo rather than act sequentially at discrete steps.

PMID- 19380878
TI  - Sam68 regulates translation of target mRNAs in male germ cells, necessary for
      mouse spermatogenesis.
AB  - Sam68 is a KH-type RNA-binding protein involved in several steps of RNA
      metabolism with potential implications in cell differentiation and cancer.
      However, its physiological roles are still poorly understood. Herein, we show
      that Sam68(-/-) male mice are infertile and display several defects in
      spermatogenesis, demonstrating an essential role for Sam68 in male fertility.
      Sam68(-/-) mice produce few spermatozoa, which display dramatic motility defects
      and are unable to fertilize eggs. Expression of a subset of messenger mRNAs
      (mRNAs) is affected in the testis of knockout mice. Interestingly, Sam68 is
      associated with polyadenylated mRNAs in the cytoplasm during the meiotic
      divisions and in round spermatids, when it interacts with the translational
      machinery. We show that Sam68 is required for polysomal recruitment of specific
      mRNAs and for accumulation of the corresponding proteins in germ cells and in a
      heterologous system. These observations demonstrate a novel role for Sam68 in
      mRNA translation and highlight its essential requirement for the development of a
      functional male gamete.

PMID- 19380879
TI  - Bax activation by the BH3-only protein Puma promotes cell dependence on
      antiapoptotic Bcl-2 family members.
AB  - It is still unclear whether the BH3-only protein Puma (p53 up-regulated modulator
      of apoptosis) can prime cells to death and render antiapoptotic BH3-binding Bcl-2
      homologues necessary for survival through its ability to directly interact with
      proapoptotic Bax and activate it. In this study, we provide further evidence,
      using cell-free assays, that the BH3 domain of Puma binds Bax at an activation
      site that comprises the first helix of Bax. We also show that, in yeast, Puma
      interacts with Bax and triggers its killing activity when Bcl-2 homologues are
      absent but not when Bcl-xL is expressed. Finally, endogenous Puma is involved in
      the apoptotic response of human colorectal cancer cells to the Bcl-2/Bcl-xL
      inhibitor ABT-737, even in conditions where the expression of Mcl-1 is down
      regulated. Thus, Puma is competent to trigger Bax activity by itself, thereby
      promoting cellular dependence on prosurvival Bcl-2 family members.

PMID- 19380880
TI  - Defining mechanisms of actin polymerization and depolymerization during dendritic
      spine morphogenesis.
AB  - Dendritic spines are small protrusions along dendrites where the postsynaptic
      components of most excitatory synapses reside in the mature brain. Morphological
      changes in these actin-rich structures are associated with learning and memory
      formation. Despite the pivotal role of the actin cytoskeleton in spine
      morphogenesis, little is known about the mechanisms regulating actin filament
      polymerization and depolymerization in dendritic spines. We show that the
      filopodia-like precursors of dendritic spines elongate through actin
      polymerization at both the filopodia tip and root. The small GTPase Rif and its
      effector mDia2 formin play a central role in regulating actin dynamics during
      filopodia elongation. Actin filament nucleation through the Arp2/3 complex
      subsequently promotes spine head expansion, and ADF/cofilin-induced actin
      filament disassembly is required to maintain proper spine length and morphology.
      Finally, we show that perturbation of these key steps in actin dynamics results
      in altered synaptic transmission.

PMID- 19380881
TI  - Dynein light chain regulates axonal trafficking and synaptic levels of Bassoon.
AB  - Bassoon and the related protein Piccolo are core components of the presynaptic
      cytomatrix at the active zone of neurotransmitter release. They are transported
      on Golgi-derived membranous organelles, called Piccolo-Bassoon transport vesicles
      (PTVs), from the neuronal soma to distal axonal locations, where they participate
      in assembling new synapses. Despite their net anterograde transport, PTVs move in
      both directions within the axon. How PTVs are linked to retrograde motors and the
      functional significance of their bidirectional transport are unclear. In this
      study, we report the direct interaction of Bassoon with dynein light chains
      (DLCs) DLC1 and DLC2, which potentially link PTVs to dynein and myosin V motor
      complexes. We demonstrate that Bassoon functions as a cargo adapter for
      retrograde transport and that disruption of the Bassoon-DLC interactions leads to
      impaired trafficking of Bassoon in neurons and affects the distribution of
      Bassoon and Piccolo among synapses. These findings reveal a novel function for
      Bassoon in trafficking and synaptic delivery of active zone material.

PMID- 19380883
TI  - Peanut allergies in children--a review.

PMID- 19380882
TI  - An 18-month-old with progressive vomiting and leg pain.

PMID- 19380884
TI  - A lethargic neonate and an infant with seizure.

PMID- 19380885
TI  - Implementation of an oral care protocol and its effects on oral mucositis.
AB  - Oral complications are commonly seen in pediatric oncology patients. Induced by
      chemotherapy or radiation, oral mucositis is a debilitating side effect that has
      much clinical significance. Oral mucositis may decrease the effectiveness of
      treatment as well as decrease the quality of life in the pediatric oncology
      patient. Therefore, it is our responsibility as health care professionals to
      reduce the incidence and/or severity of mucositis as much as possible. One
      intervention that has been proven to be successful is basic oral hygiene
      implemented through an oral care protocol. It is important that nurses are
      educated on the significance of adequate dental hygiene and the process and need
      for institutional change of protocols. Nurses and other health care professionals
      can positively influence patient care by incorporating the evidence-based
      practice of an oral care protocol- improving consistency of care while promoting
      an intervention of proven benefit against oral mucositis.

PMID- 19380887
TI  - Perceptions of perceptual learning. Editorial.

PMID- 19380886
TI  - The Hippocratic Oath, effect size, and utility theory.
AB  - To be consistent with the Hippocratic Oath, this article proposes that a
      physician choose that treatment that has the greatest chance of giving the
      patient an outcome no worse than the uncertain outcome an untreated patient would
      experience. As this article shows, this specifies the utility function that the
      physician should use in choosing among treatments. This utility function,
      although varying with the life circumstances of the patient, need not reflect the
      patient's utility function. This Hippocratic utility function can be estimated
      with an effect size measure similar to the stochastic superiority and common
      language effect size measures used in the statistical analysis of experiments.

PMID- 19380888
TI  - Varieties of perceptual learning.
AB  - Although most studies of perceptual learning in human participants have
      concentrated on the changes in perception assumed to be occurring, studies of
      nonhuman animals necessarily measure discrimination learning and generalization
      and remain agnostic on the question of whether changes in behavior reflect
      changes in perception. On the other hand, animal studies do make it easier to
      draw a distinction between supervised and unsupervised learning. Differential
      reinforcement will surely teach animals to attend to some features of a stimulus
      array rather than to others. But it is an open question as to whether such
      changes in attention underlie the enhanced discrimination seen after unreinforced
      exposure to such an array. I argue that most instances of unsupervised perceptual
      learning observed in animals (and at least some in human animals) are better
      explained by appeal to well-established principles and phenomena of associative
      learning theory: excitatory and inhibitory associations between stimulus
      elements, latent inhibition, and habituation.

PMID- 19380889
TI  - Roles of attention in perceptual learning from perspectives of psychophysics and
      animal learning.
AB  - The role of attention in perceptual learning has been a topic of controversy.
      Sensory psychophysicists/physiologists and animal learning psychologists have
      conducted numerous studies to examine this role; but because these two types of
      researchers use two very different lines of approach, their findings have never
      been effectively integrated. In the present article, we review studies from both
      lines and use exposure-based learning experiments to discuss the role of
      attention in perceptual learning. In addition, we propose a model in which
      exposure-based learning occurs only when a task-irrelevant feature is weak. We
      hope that this article will provide new insight into the role of attention in
      perceptual learning to the benefit of both sensory psychophysicists/physiologists
      and animal learning psychologists.

PMID- 19380890
TI  - Perceptual learning in human and nonhuman animals: a search for common ground.
AB  - Perceptual learning has been extensively studied in both human and nonhuman
      animals, but the two lines of research have, for the most part, developed
      independently, addressing seemingly rather different issues by rather different
      methods. It has been argued, however, that analysis of the disparate phenomena
      studied in experiments on perceptual learning reveals that in all the studies,
      the essential feature is that appropriate training allows behavior to come to be
      controlled by the unique features, rather than by the common features, of similar
      stimuli. It has further been argued that experiments with nonhuman animals have
      established the existence of a range of learning processes that allow this to
      occur, and that these processes have general relevance, applying to humans as
      well as to animals.

PMID- 19380891
TI  - Perceptual learning and representational learning in humans and animals.
AB  - Traditionally, perceptual learning in humans and classical conditioning in
      animals have been considered as two very different research areas, with separate
      problems, paradigms, and explanations. However, a number of themes common to
      these fields of research emerge when they are approached from the more general
      concept of representational learning. To demonstrate this, I present results of
      several learning experiments with human adults and infants, exploring how
      internal representations of complex unknown visual patterns might emerge in the
      brain. I provide evidence that this learning cannot be captured fully by any
      simple pairwise associative learning scheme, but rather by a probabilistic
      inference process called Bayesian model averaging, in which the brain is assumed
      to formulate the most likely chunking/grouping of its previous experience into
      independent representational units. Such a generative model attempts to represent
      the entire world of stimuli with optimal ability to generalize to likely scenes
      in the future. I review the evidence showing that a similar philosophy and
      generative scheme of representation has successfully described a wide range of
      experimental data in the domain of classical conditioning in animals. These
      convergent findings suggest that statistical theories of representational
      learning might help to link human perceptual learning and animal classical
      conditioning results into a coherent framework.

PMID- 19380892
TI  - Human and animal perceptual learning: some common and some unique features.
AB  - A selective summary of the four contributions to this special issue of Learning &
      Behavior on perceptual learning is presented. Mackintosh and Hall propose an
      associative analysis of perceptual learning. It is argued that Tsushima and
      Watanabe's psychophysical evidence and Fiser's Bayesian-modeling work represent
      (in different ways) challenges to the associative approach. Some tentative
      suggestions are explored with regard to how animal learning theorists might meet
      these challenges. Finally, the role of awareness in perceptual learning is
      briefly examined.

PMID- 19380893
TI  - A differential-outcomes effect using hedonically nondifferential outcomes with
      delayed matching to sample by pigeons.
AB  - When differential outcomes follow correct responses to each of two comparison
      stimuli in matching to sample, relative to the appropriate control condition,
      higher matching accuracy is typically found, especially when there is a delay
      between the sample and the comparison stimuli. In two experiments, we examined
      whether this differential-outcomes effect depends on using outcomes that differ
      in hedonic value (e.g., food vs. water). In Experiment 1, we found facilitated
      retention when a blue houselight followed correct responses to one comparison
      stimulus and a white houselight followed correct responses to the other, prior to
      nondifferential presentations of food. In Experiment 2, we found facilitated
      retention again when a blue houselight followed correct responses to one
      comparison stimulus and a tone followed correct responses to the other, prior to
      nondifferential presentations of food. The results of both experiments indicate
      that the differential-outcomes effect does not depend on a difference in hedonic
      value of the differential outcomes, and they suggest that outcome anticipations
      consisting of relatively arbitrary but differential stimulus representations can
      serve as cues for comparison choice.

PMID- 19380894
TI  - A landmark blocks searching for a hidden platform in an environment with a
      distinctive shape after extended pretraining.
AB  - In the blocking phase of three experiments, rats had to find a submerged platform
      beneath a spherical landmark in one corner of a triangular pool. Prior to this
      treatment, they were required to find the platform relative to either a sphere
      above it (blocking groups) or a rod attached to it (control groups). The position
      of the platform changed from trial to trial for the initial training. The sphere
      did not restrict learning about the geometric cues provided by the triangular
      arena in the blocking phase when 12 sessions of initial training took place in
      either the triangular (Experiment 1) or a circular (Experiment 3) pool. Blocking
      was observed, however, after 24 sessions of initial training in either the
      triangular (Experiment 2) or the circular (Experiment 3) pool. Thus, blocking of
      geometric cues by a landmark is possible after extended initial training with the
      blocking cue.

PMID- 19380895
TI  - Sensory-specific associations in flavor-preference reversal learning.
AB  - In two experiments, we examined the effect of reversal learning on the status of
      initially learned associations. In Experiment 1, thirsty rats were first taught
      to associate one flavor with sucrose and another flavor with Polycose. These
      relations were then reversed in a subsequent phase. One of the nutrients was then
      devalued by being paired with lithium chloride. The results of a two-bottle
      flavor-choice test revealed that the most recently learned associations governed
      performance. In Experiment 2, we aimed to discern whether the initially learned
      associations in Experiment 1 were weakened or masked by reversal learning. In
      order to address this question, either a 1-day (Group Immediate) or a 21-day
      (Group Delayed) retention interval was interpolated between the reversal and
      devaluation phases. Subsequent flavor-choice tests revealed that Group Immediate
      avoided the flavor most recently associated with the devalued nutrient but that
      Group Delayed avoided the flavor that was initially associated with the devalued
      nutrient. These findings suggest that the second-learned associations do not
      erase, but transiently mask, the first-learned associations, which subsequently
      recover over a retention interval. These results suggest a parallel in the
      mechanisms of extinction and reversal learning.

PMID- 19380896
TI  - The search for symmetry: 25 years in review.
AB  - It has been 25 years since the publication of Sidman et al.'s (1982) report on
      the search for symmetry in nonhuman animals. They attributed their nonhuman
      subjects' failure to the absence of some critical experiences (e.g., exemplar
      training, control of location variables, and generalized identity matching).
      Since then, species ranging from rats to chimpanzees have been tested on
      symmetry, and the results have been equivocal. Twenty-four investigations of
      symmetry in nonhumans are reviewed to determine whether the underlying factors
      first addressed by Sidman et al. (1982) have been verified and whether new
      factors have been identified. The emergent picture shows that the standard
      procedures as typically implemented on a three-key apparatus are insufficient by
      themselves to produce emergent symmetry in nonhumans. Recent successful
      demonstrations of symmetry in sea lions and pigeons have clarified certain
      important stimulus control variables (i.e., select and reject control) and
      suggest avenues for future research. Reliable symmetry may be achievable with
      nonhumans if training and test procedures that encourage compatible stimulus
      control topographies and relations are designed.

PMID- 19380897
TI  - Individual differences: either relational learning or item-specific learning in a
      same/different task.
AB  - Three pigeons were trained in a three-item simultaneous same/different task.
      Three of six stimulus combinations were not trained (untrained set) and were
      tested later. Following acquisition, the subjects were tested with novel stimuli,
      the untrained set, training-stimulus inversions, and object shape and color
      manipulations. There was no novel-stimulus transfer--that is, no abstract-concept
      learning. Two pigeons showed partial transfer to untrained pairs and good
      transfer to stimulus inversions, suggesting that they had learned the
      relationship between the stimuli. Lack of transfer by the third pigeon suggests
      item-specific learning. The somewhat surprising finding of relational learning by
      2 pigeons with only six training pairs suggests restricted-domain relational
      learning that was controlled more by color than by shape features. Individual
      differences of item-specific learning by 1 pigeon and relational learning by 2
      others demonstrate that this task can be learned in different ways and that
      relational learning can occur in the absence of novel-stimulus transfer.

PMID- 19380898
TI  - Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe
      and/or simvastatin in men.
AB  - This study evaluates changes in cholesterol balance in hypercholesterolemic
      subjects following treatment with an inhibitor of cholesterol absorption or
      cholesterol synthesis or coadministration of both agents. This was a randomized,
      double blind, placebo-controlled, four-period crossover study to evaluate the
      effects of coadministering 10 mg ezetimibe with 20 mg simvastatin
      (ezetimibe/simvastatin) on cholesterol absorption and synthesis relative to
      either drug alone or placebo in 41 subjects. Each treatment period lasted 7
      weeks. Ezetimibe and ezetimibe/simvastatin decreased fractional cholesterol
      absorption by 65% and 59%, respectively (P < 0.001 for both relative to placebo).
      Simvastatin did not significantly affect cholesterol absorption. Ezetimibe and
      ezetimibe/simvastatin increased fecal sterol excretion (corrected for dietary
      cholesterol), which also represents net steady state cholesterol synthesis, by
      109% and 79%, respectively (P < 0.001). Ezetimibe, simvastatin, and
      ezetimibe/simvastatin decreased plasma LDL-cholesterol by 20, 38, and 55%,
      respectively. The coadministered therapy was well tolerated. The decreases in net
      cholesterol synthesis and increased fecal sterol excretion yielded nearly
      additive reductions in LDL-cholesterol for the coadministration of ezetimibe and
      simvastatin.

PMID- 19380899
TI  - Introduction to special issue 'Alcohol, media and message'.

PMID- 19380900
TI  - The importance of keeping regular: accurate guidance to the public on low-risk
      drinking levels.
AB  - AIM: The aim of this study was to argue that recommendations to the general
      public on daily amounts for low-risk alcohol consumption must retain the word
      'regular' in order to avoid being rejected. METHOD: Narrative review of the
      evidence-base for daily limits to alcohol consumption, the guidance the public
      actually receives in the UK and media reactions to this guidance. RESULTS:
      Evidence for daily limits (not more than 3-4 units for men and 2-3 units for
      women) rests on epidemiological surveys that enquire about 'average' or 'usual'
      amounts of consumption and this is reflected by the use of 'regular' or
      'consistent' in the UK Government's Sensible Drinking report in 1995 and in
      guidance currently issued by the English Department of Health. In contrast,
      guidance the public actually receives often omits the word 'regular' and implies
      that the limits in question are maximum daily amounts. Media reactions to this
      inaccurate information suggest that the general public is likely to find these
      recommendations incredible and to reject them. CONCLUSION: If guidance to the
      public on daily drinking amounts is to stand any chance of being credible and
      effective, it must be accurate and must therefore retain the word 'regular'.

PMID- 19380901
TI  - Calcium-activated chloride currents prolongs the duration of contractions in
      pregnant rat myometrial tissue.
AB  - We investigated the importance of pharmacologically blocking calcium-activated
      chloride (I(Cl(Ca))) and L-type calcium currents on isometric contractions of
      strips of D21 pregnant rat myometrial tissue, while simultaneously measuring the
      electrical activity of the tissue strips with extracellular contact electrodes.
      When measured with contact electrodes, the duration of the spiking activity
      directly reflects the duration of the tissue-level plateau potential. We
      correlated the number of spikes, durations of spiking activity, and the spiking
      frequencies with changes of the area under the force curves as a function of
      exposure to low doses of anthracene-9-carboxylate (9-AC, a non-specific Cl
      channel blocker), chlorotoxin (a specific I(Cl(Ca)) blocker) and nifedipine (an L
      type calcium channel blocker). The area under the force curve was measured only
      during spiking electrical activity, thereby separating pharmacological effects on
      tissue relaxation from those that modulate force production. Blocking chloride
      channels reduced impulse, shortened the duration of spiking activity, and reduced
      the number of spikes generated in each contraction. This was observed without a
      change in the frequency of spike production or a reduction of peak force.
      Nifedipine reduced impulse, shortened the duration of spiking activity, and
      reduced the number of spikes. In contrast to chloride channel blockade,
      nifedipine reduced maximum spike frequency and peak force. Taken together, our
      data suggest that blocking L-type calcium channels reduces impulse directly by
      reducing peak force, and indirectly by reducing activation of I(Cl(Ca)) , which
      shortens the duration of the contraction.

PMID- 19380902
TI  - Review: luminescence as a tool to assess pelvic endometriosis development in
      murine models.
AB  - Classic murine endometriosis models may be insufficient to evaluate the effect of
      therapeutic agents on endometriosis development, because the process of
      identification and measurement of induced lesions is often impeded, as implants
      are small and embedded in murine tissue. In this context, as summarized in the
      current review, luminescence techniques have proved useful for identifying and
      visualizing or quantifying endometriotic transplants. They are also a valuable
      tool for endometrial cell tracking in live animals, yielding further information
      by adding spatial and temporal dimensions to biological processes in vivo. Such
      approaches involve transplanting luminescently labeled murine or human
      endometrium into animals. Two main strategies are applied to label endometrium
      before injection: use of genetically modified tissue or tissue labeled with a
      fluorescent dye. Each model has its advantages and disadvantages, the choice of
      model depends on the study objectives/design (long- or short-term studies,
      homologous or heterologous model).

PMID- 19380903
TI  - Placental and fetal hemodynamics after labetalol or pindolol in a sheep model of
      increased placental vascular resistance and maternal hypertension.
AB  - We investigated the effects of labetalol and pindolol on uterine, placental, and
      fetal hemodynamics following norepinephrine-induced maternal hypertension in a
      sheep model of increased placental vascular resistance. Also, we examined fetal
      and placental hemodynamic responses to acute hypoxemia after antihypertensive
      medication. Norepinephrine increased maternal heart rate (HR), mean arterial
      pressure (MAP) and uterine vascular resistance (R(UtA)), and decreased uterine
      volume blood flow (Q(UtA)). Both labetalol and pindolol decreased maternal HR,
      MAP, and R(UtA), but did not restore Q(UtA). Fetal MAP was unaffected while fetal
      HR and placental volume blood flow (Q(UA)) decreased and placental vascular
      resistance increased. During hypoxemia, which was induced by decreasing maternal
      inspiratory oxygen fraction, all these parameters remained unchanged in the
      labetalol group while fetal HR increased and Q(UA) further decreased in the
      pindolol group. We conclude that labetalol and pindolol may compromise uterine
      and placental hemodynamics. Hypoxemic stress provokes divergent hemodynamic
      responses in fetuses exposed to these differently acting adrenoceptor
      antagonists.

PMID- 19380904
TI  - Telomeric RNAs mark sex chromosomes in stem cells.
AB  - Telomeric regions are known to be transcribed in several organisms. Although
      originally reported to be transcribed from all chromosomes with enrichment near
      the inactive X of female cells, we show that telomeric RNAs in fact are enriched
      on both sex chromosomes of the mouse in a developmentally specific manner. In
      female stem cells, both active Xs are marked by the RNAs. In male stem cells,
      both the X and the Y accumulate telomeric RNA. Distribution of telomeric RNAs
      changes during cell differentiation, after which they associate only with the
      heterochromatic sex chromosomes of each sex. FISH mapping suggests that
      accumulated telomeric RNAs localize at the distal telomeric end. Interestingly,
      telomeric expression changes in cancer and during cellular stress. Furthermore,
      RNA accumulation increases in Dicer-deficient stem cells, suggesting direct or
      indirect links to RNAi. We propose that telomeric RNAs are tied to cell
      differentiation and may be used to mark pluripotency and disease.

PMID- 19380906
TI  - A morphological approach for the fovea location in color fundus images.
AB  - This paper presents a novel method for the detection of the fovea center in color
      fundus images. The method was evaluated using a set of 89 images from the
      DIARETDB1 project, which contains images presenting normal and pathological
      situations. Using the Mean Absolute Distance (MAD) as a metric, we report 7.37+/
      8.89 (mean +/- standard deviation) detection performance for the fovea center
      which represents an improvement in comparison to other state-of-the-art methods
      in the literature.

PMID- 19380905
TI  - Telomere maintenance and survival in saccharomyces cerevisiae in the absence of
      telomerase and RAD52.
AB  - Telomeres are essential features of linear genomes that are crucial for
      chromosome stability. Telomeric DNA is usually replenished by telomerase.
      Deletion of genes encoding telomerase components leads to telomere attrition with
      each cycle of DNA replication, eventually causing cell senescence or death. In
      the Saccharomyces cerevisiae strain W303, telomerase-null populations bypass
      senescence and, unless EXO1 is also deleted, this survival is RAD52 dependent.
      Unexpectedly, we found that the S. cerevisiae strain S288C could survive the
      removal of RAD52 and telomerase at a low frequency without additional gene
      deletions. These RAD52-independent survivors were propagated stably and exhibited
      a telomere organization typical of recombination between telomeric DNA tracts,
      and in diploids behaved as a multigenic trait. The polymerase-delta subunit Pol32
      was dispensable for the maintenance of RAD52-independent survivors. The incidence
      of this rare escape was not affected by deletion of other genes necessary for
      RAD52-dependent survival, but correlated with initial telomere length. If W303
      strains lacking telomerase and RAD52 first underwent telomere elongation, rare
      colonies could then bypass senescence. We suggest that longer telomeres provide a
      more proficient substrate for a novel telomere maintenance mechanism that does
      not rely on telomerase, RAD52, or POL32.

PMID- 19380907
TI  - Integrating evidence-based interventions into client care plans.
AB  - Within the mental health care system, there is an opportunity to improve patient
      safety and the overall quality of care by integrating clinical practice
      guidelines with the care planning process through the use of information
      technology. Electronic assessment tools such as the Resident Assessment Inventory
      - Mental Health (RAI-MH) are widely used to identify the health care needs and
      outcomes of clients. In this knowledge translation initiative, an electronic care
      planning tool was enhanced to include evidence-based clinical interventions from
      schizophrenia guidelines. This paper describes the development of a mental health
      decision support prototype, a field test by clinicians, and user experiences with
      the application.

PMID- 19380908
TI  - Anemia analyzer: algorithm and reflex testing in clinical practice leading to
      efficiency and cost savings.
AB  - Anemia is a common disease affecting about 3.5 million people in the United
      States. In present day clinical practice, a clinician makes a diagnosis of anemia
      based on low hemoglobin levels discovered during a complete blood count (CBC)
      test. If the etiology of the anemia is not readily apparent, the clinician orders
      additional testing to discover the cause of the anemia. Which tests are ordered,
      in what order these tests are run, and how the information gathered from the
      tests is used is based primarily on the individual physician's knowledge and
      expertise. Using this system to determine the cause of anemia is not only labor
      and resource intensive but it carries a potential for morbidity and an occasional
      mortality. Utilizing previously published data, we created an algorithmic
      approach to analyze the cause of anemia in the majority of cases. The algorithm
      accepts as input three parameters from a CBC test: (1) mean corpuscular volume,
      (2) red cell distribution width, and (3) reticulocyte count. With these three
      parameters, the algorithm generates a probable etiology of the anemia.
      Additionally, the algorithm will automatically order reflex tests needed to
      confirm the diagnosis. These reflex tests can be modified depending on the
      policies of the institution using the algorithm, as different institutions may
      order different tests based on availability and costs. This is a simple algorithm
      that could be integrated into the CBC test output. When a low hemoglobin level is
      found, the algorithm suggests the probable etiology and orders reflex tests if
      they are desired. Such an approach would not only provide cost efficiency and
      time savings but would also elevate the level of every clinician ordering a CBC
      to that of an expert hematologist.

PMID- 19380910
TI  - Benefits and challenges of health information systems for operations research: an
      illustrative example to improve surgical scheduling.
AB  - Operations research (OR) is playing an increasing role in the support of many
      health care initiatives. However one of the main challenges facing OR
      practitioners is the availability and the integrity of operations data. Hospital
      information systems (HIS) are often designed with a clinical or accounting focus
      and may lack the data necessary for operational studies. In this paper, we
      illustrate the data processing methods and data challenges faced by our team
      during a study of surgical scheduling practices at the Vancouver Island Health
      Authority. We also provide some general recommendations to improve HIS from an
      operations perspective. In general, more integration between operations
      researchers and HIS specialists are required to support ongoing operational
      improvements in the health care sector.

PMID- 19380909
TI  - Process data: a means to measure operational performance and implement advanced
      analytical models.
AB  - We present the case of an ambulatory clinic in which an operational review was
      conducted to identify opportunities for efficiency in appointment scheduling and
      capacity allocation. We required process data to compare that which was planned
      to that which actually happened and to develop advanced analytical models.
      Similar to other health care studies, these data proved to be limited or non
      existent. Consequently we had to conduct a time-consuming collection of
      operational metrics. We make recommendations for the perpetual collection of
      process data for modeling and simulation.

PMID- 19380911
TI  - Toward automatic detection and prevention of adverse drug events.
AB  - Adverse Drug Events (ADE) due to medication errors and human factors are a major
      public health issue. They endanger patient safety and cause considerable extra
      healthcare costs. The European project PSIP (Patient Safety through Intelligent
      Procedures in medication) aims to identify and prevent ADE. Data mining of the
      structured hospital data bases will give a list of observed ADE with frequencies
      and probabilities, thereby giving a better understanding of potential risks. The
      main objective of the project is to develop innovative knowledge based on the
      mining results and to deliver to professionals and patients, in the form of
      alerts and decision support functions, a contextualized knowledge fitting the
      local risk parameters.

PMID- 19380912
TI  - Modeling knowledge resource selection in expert librarian search.
AB  - Providing knowledge at the point of care offers the possibility for reducing
      error and improving patient outcomes. However, the vast majority of the
      physician's information needs are not met in a timely fashion. The research
      presented in this paper characterizes an expert librarian's search strategies as
      it pertains to the selection and use of various electronic information resources.
      The 10 searches conducted by the librarian to address the physician's information
      needs varied in terms of complexity and question type. The librarian employed a
      total of 10 resources and used as many as 7 in a single search. The longer term
      objective is to model the sequential process in sufficient detail as to be able
      to contribute to the development of intelligent automated search agents.

PMID- 19380913
TI  - Analysis of acuity trends using Resource Intensity Weights via the CIHI Portal.
AB  - One key to revolutionizing health care with informatics is the ability of
      decision-makers to access and analyze relevant data in a timely and efficient
      manner. Inspired by the demand for timely access to hospitalization data in
      Canada, CIHI Portal is an innovative web-based analytical tool which combines
      leading technology and data for decision support analysis. Hospitals, regional
      health authorities and ministries of health can use CIHI Portal to access
      comparable, pan-Canadian healthcare data for health data analysis, collaboration
      and dissemination. The goal of CIHI Portal is to support health care decision
      makers in their local and regional health care planning and to answer service
      delivery questions.The Capital Health region in Alberta used Resource Intensity
      Weights (RIW) to investigate claims that patients within their region were
      getting sicker over the past few years and that additional resources would be
      required in the future. Using the CIHI Portal, Capital Health conducted an
      analysis on historical trends in the average RIWs Average Resource Intensity
      Weight is calculated as the total Resource Intensity Weight (RIW) divided by the
      total number of inpatient separations. and found that although typical patients
      were not using a greater amount of resources, there was definitely an increase in
      the amount of resources consumed by atypical patients. Information contained in
      the analysis influenced budgeting, fund reallocation and health care planning.
      CIHI Portal has proven to be a reliable tool for data access, information sharing
      and knowledge exchange. It has enhanced decision support services within the
      Capital Health region.

PMID- 19380914
TI  - The University of Victoria Interdisciplinary Electronic Health Record Educational
      Portal.
AB  - Use of Electronic Health Record (EHR) systems is increasing globally. However,
      adoption rates of Health Information Systems (HISs) continue to remain poor. To
      improve adoption rates, there is need to provide greater HIS experience to health
      professionals and informaticians in health and biomedicine during their
      undergraduate and graduate education. A recent review of the health professional
      educational curricula (i.e., medicine, nursing, allied health and
      health/biomedical informatics) revealed that they provide only limited exposure
      to EHRs. In response to this educational need, the authors have developed the
      University of Victoria Interdisciplinary Electronic Health Record Educational
      Portal (UVicIED-EHR Portal). This unique, web-based portal allows students of the
      health professions and practicing professionals to access and interact with a set
      of representative EHR HIS solutions using the web. The portal, which links to
      several EMRs, EPRs and PHRs, has been used by several health professional
      educational programs in medicine, nursing and health informatics. It provides
      practicing health and health/biomedical informatics professionals, for example,
      managers and directors, with opportunities to access and review EHR systems. The
      portal has been used successfully in the classroom, laboratory and with distance
      education to give hands-on experience with a variety of HISs and their
      components.

PMID- 19380915
TI  - Integrating point-of-care technology into the midwifery curricula.
AB  - At the University of Technology, Sydney (UTS), Australia, a pilot study was
      conducted to introduce and integrate mobile point-of-care technologies into the
      clinical laboratory experiences of students in the Bachelor of Midwifery program.
      The pilot study was a collaborative project between Intel Healthcare and the
      Faculty of Nursing Midwifery and Health at UTS and was conducted using Intel's
      mobile clinical assistants (MCA). Through role playing, students were exposed to
      a number of case scenarios drawn from authentic midwifery practice. The MCA was
      used to gain information such as test results, clinical practice protocols, and
      best evidence guidelines. The students were expected to discuss the information
      with the woman. Following the activity, students completed an online survey to
      identify the impact of the MCA on the role-playing situations. They also
      participated in a focus group where they could discuss the use of the point-of
      care technology in relation to preparation for practice. Results from these
      evaluations indicated that the students were positive about using the MCA in
      simulation sessions and they also considered that this technology would be
      helpful in their practice. It is hoped that the use of such point-of-care
      technology will be integrated across the Faculty's pre-registration midwifery and
      nursing programs to provide students with access to the most recent information
      technology innovations in health care.

PMID- 19380916
TI  - Incorporation of medical informatics and information technology as core
      components of undergraduate medical education - time for change!
AB  - It is generally accepted that Information Technology (IT) is a highly desirable
      and a very necessary ingredient of modern health care. Review of available
      literature reveals a paucity of medical informatics and information technology
      courses in undergraduate medical curricula and a lack of research to assess the
      effectiveness of medical informatics in undergraduate medical education. The need
      for such initiatives is discussed and a pilot project is described that evaluated
      the effectiveness of education in the use of Electronic Medical Record (EMR)
      applications. Educational activities, for example, could be medical students
      conducting virtual medical encounters or interacting with EMR applications. An
      EMR application, which was used in several related projects, has been adapted to
      the educational environment: standardized patient records can be created and
      cloned so that individual students can interact with a "standard" patient and
      alter the patient's data.

PMID- 19380917
TI  - The Engineering 4 Health Challenge - an interdisciplinary and intercultural
      initiative to foster student engagement in B.C. and improve health care for
      children in under-serviced communities.
AB  - This paper describes the Engineering 4 Health (E4H) Challenge, an
      interdisciplinary and intercultural initiative that, on the one hand, seeks to
      improve health education of children in under-serviced communities and, on the
      other, seeks to attract students in British Columbia to professions in
      engineering and health. The E4H Challenge engages high school and university
      students in BC to cooperatively design and develop health information and
      communication technology (ICT) to educate children living in under-serviced
      communities. The E4H Challenge works with the One Laptop Per Child (OLPC) program
      to integrate applications for health awareness into the school programs of
      communities in developing countries. Although applications developed by the E4H
      Challenge use the low-cost, innovative XO laptop (the "$100 laptop" developed by
      the OLPC foundation) the software can also be used with other inexpensive
      hardware.

PMID- 19380918
TI  - An innovative learning experience for entry to eHealth careers.
AB  - We describe an innovative educational program that provides an easily-accessible
      introduction to Applied Health Informatics (AHI) in an effort to attract new
      trainees to this discipline. We call this program the AHI Bootcamp. It includes
      an intense, interactive, but brief on-site program, with the majority of its
      content delivered in approximately 80 hours of on-line presentations. The AHI
      Bootcamp introduces individuals, who have a broad spectrum of backgrounds but
      little or no knowledge of Health Informatics (HI), to the nature, concepts,
      methods, tools and applications of HI to address information-based challenges in
      health maintenance and health care delivery. AHI is the discipline that is
      concerned with the planning, procurement, deployment, implementation, management,
      effective use, and evaluation of informatics solutions in the health space. This
      program targets the high profile areas of AHI, orienting participants to the
      pursuit of broader and deeper explorations in the field.

PMID- 19380919
TI  - Information management framework; a model for clinical departments.
AB  - The information management system of Department of Critical Care Medicine in
      Calgary Health Region was modeled using a departmental information management
      framework. The clinical, administrative, research and educational, decision
      making and quality improvement information needs of the department are served by
      the system.

PMID- 19380920
TI  - Clinical support in primary and ambulatory care: Canadian lessons to be learned
      from the UK patient Summary Care Record (SCR) initiative.
AB  - There is an increasing requirement for interdisciplinary teams to share patient
      data to ensure optimal care. Healthcare providers in all settings from Emergency
      Medicine to long-term care management need access to patient information. In the
      UK, developments to address the need for information sharing have uncovered
      issues that the Canadian eHealth establishment would do well to heed when
      undertaking its own initiatives.

PMID- 19380921
TI  - Technical and architectural issues in deploying electronic health records (EHRs)
      over the WWW.
AB  - In this paper technical and architectural issues are described in deploying
      electronic health records (EHRs) over the WWW. The project described involved
      deployment of EHRs that have been designed to serve in the education of health
      professionals and health/biomedical informaticians. In order to allow for
      ubiquitous access to a range of EHRs remotely an architecture was designed with
      three layers: (a) the "Internet" or remote user access layer (2) the "Perimeter
      Network", or middle firewall security and authentication layer (3) the "HINF EHR
      Network", consisting of the internal servers hosting EHR applications and
      databases. The approaches allow for a large number of remote users running a
      range of operating systems to access the educational EHRs from any location
      remotely. Virtual machine (VM) technology is employed to allow multiple versions
      and platforms of operating systems to be installed side-by-side on a single
      server. Security, technical and budgetary considerations are described as well as
      past and current applications of the architecture for a number of projects for
      the education of health professionals in the area of electronic health records.

PMID- 19380922
TI  - Ontario's province-wide paediatric electronic health record.
AB  - The electronic Child Health Network (eCHN) is an advanced implementation of an
      electronic health record (EHR). This is a case study of the building of an
      integrated and shared EHR from multiple systems at multiple sites for the benefit
      of patients and clinicians. Optimal patient care requires that information about
      a person's overall health and interactions with the health care system be
      available to the appropriate providers when and where it is needed. eCHN is a
      pioneering response to the need for such shared records. A key to its success is
      that it is a flexible, scalable, open, multi-vendor solution designed to work
      with existing hospital systems and other networks. As Canada's largest
      functioning integrated EHR, eCHN is serving three million people and transforming
      the quality of health record keeping and clinical decision-making. eCHN enables
      health care providers across Ontario to share accurate patient data - in real
      time.

PMID- 19380923
TI  - Failure of electronic medical records in Canada: a failure of policy or a failure
      of technology?
AB  - This paper utilizes three frameworks described in the literature to better
      understand the reasons why Canada lags other OECD countries in EMR
      implementation. First, we use an EMR policy framework to evaluate three
      provincial EMR implementation programs across Canada. Second, we use an EMR
      implementation multi-theoretical framework that is predictive of EMR success to
      evaluate those same programs. Finally, we use a cost-benefit framework developed
      in the USA to compare the cost-benefits of EMR implementations in Canada compared
      to those in the USA. We draw conclusions and make recommendations based on our
      findings.

PMID- 19380924
TI  - Is it appropriate, or ethical, to use health data collected for the purpose of
      direct patient care to develop computerized predictive decision support tools?
AB  - The increasing use of clinical decision support systems (CDSS) to assist
      clinicians in decision-making is pushing the limits of information technology.
      The emergence of Electronic Health Records (EHR) coupled with enriched health
      information standards such as HL7 CDA, SNOMED, ICD-10 and LOINC have provided a
      rich environment for massive data collection and analysis by healthcare
      providers. This immense increase in data collection has also provided a gateway
      for the application of various data mining techniques on clinical datasets so as
      to measure health status (i.e. function, comfort and likelihood of dying) of
      patients. In measuring health status, many clinicians have opted to use CDSS to
      assist in decision-making and enhance clinical experience. However, even as the
      use of CDSS in clinicians' office continues to grow, the question that remains in
      the minds of many patients and the general public is whether it is appropriate,
      or ethical, for researchers to use health data collected for the purpose of
      direct patient care to develop computerized predictive decision support tool. In
      this paper, a systematic review is used to highlight the relevant technical
      barriers and ethical issues surrounding the secondary use of health data in
      developing CDSS.

PMID- 19380925
TI  - National health information management/information technology strategies in Hong
      Kong, Taiwan and Singapore.
AB  - A national health information management/information technology (IM/IT) strategy
      is crucially important for a country in planning and implementing healthcare
      priorities. However, little comparative research has been performed in this area,
      especially in Asian countries. This paper reviews, assesses and compares the
      healthcare systems, as well as the national health IM/IT initiatives and
      strategies in Hong Kong, Taiwan and Singapore. Although the proportion of public
      and private health services, IT infrastructure development, and government
      involvement in these three jurisdictions are different, they experience similar
      challenges with limited resources. By outlining the approaches being taken in the
      three Asian jurisdictions, this paper provides comparison, evaluation and
      insights that may be useful to other jurisdictions.

PMID- 19380926
TI  - Pharmacy information systems in Canada.
AB  - The goal of Canada Health Infoway is to provide at least 50% of all Canadians
      with an electronic health record (EHR) by 2010. The goal of the Infoway Drug
      Information Systems Program is to develop an interoperable drug information
      system that will keep each patient's medication history: prescribed and dispensed
      drugs, allergies, ongoing drug treatment, etc. Drug and drug-interaction checks
      will be performed automatically and added to the patients' drug profiles.
      Physicians and pharmacists will be supplied with data to support appropriate and
      accurate prescribing and dispensing, thereby avoiding adverse drug interactions
      and drug-related deaths [1]. This paper describes Canadian developments in
      pharmacy eHealth. It presents the results of the Pharmacy Informatics Pharmacy
      Special Networks (PSN) survey about computer systems used in hospital pharmacies
      across Canada including information concerning Computerized Provider Order Entry
      (CPOE) systems deployed; which may reduce the number of errors in orders.

PMID- 19380927
TI  - Findings from evaluations of the benefits of diagnostic imaging systems.
AB  - Canada Health Infoway and its partners in the provinces and territories have made
      significant investments in diagnostic imaging (DI) systems across Canada.
      Infoway's DI Investment Program is to implement storage for diagnostic digital
      images so that clinicians can view images regardless of where they are stored.
      Specifically, Infoway is investing in Picture Archiving and Communications
      Systems (PACS), which are those systems with the modern digital archiving
      capabilities used by DI systems.eHealth implementations in Canada are responsible
      for demonstrating the value of eHealth investments to users and stakeholders and
      driving benefit optimization. Canada has a rich set of results from British
      Columbia, Ontario, Nova Scotia, and Newfoundland and Labrador due to early
      Infoway investments in DI systems. The positive evaluation results are
      encouraging but they indicate that continued effort and investment are required
      to fully realize the benefits. This paper discusses findings from evaluation
      studies, the pan-Canadian aggregation study, and possibilities for benefit
      optimization from investments made in the Electronic Health Record (EHR).

PMID- 19380928
TI  - Availability and usage of ICT applications among European primary care
      physicians.
AB  - While differences in Information and Communication Technology (ICT)
      infrastructure in European general practices are decreasing more and more, actual
      use rates - in particular, for more advanced applications - are about as
      different as the languages spoken by GPs throughout the European Union. This is
      one finding of a representative survey among GPs in Europe carried out by
      empirica on behalf of the European Commission. The resulting patchwork pattern of
      eHealth use shows that there is still some distance to go before all the
      potential benefits of eHealth in general practice can be reaped by all the EU
      member states.

PMID- 19380929
TI  - How can we know whether short term trends in a hospital's HSMR are significant?
AB  - The Hospital Standardized Mortality Ratio (HSMR) has been chosen by CIHI as its
      primary mortality measure. The indirect standardization used in the calculation
      of HSMR does not allow for valid comparison between hospitals but it does invite
      the assessment of quarterly trends in hospital mortality. However, statistical
      methods for assessing HSMR trends are not well-developed. In 2007 one large
      hospital in our health authority had four consecutive quarters of apparently
      increasing HSMR. As a result, we needed to assess the significance of this trend
      which, if it were to continue into the next quarter, would lead to an HSMR that
      significantly exceeded 100. We explored four methods to assess statistical
      significance of time trends in HSMR data: the WINPEPI "Describe" module, the
      CUSUM representation of Observed-Expected differences, the Variable Life Adjusted
      Display (VLAD) plots with CUSUM overlays, and the Change Point Analysis using
      Monte Carlo simulation.

PMID- 19380930
TI  - An embarrassment of data: how e-assessments are supporting front line clinical
      decisions and quality management across Canada and around the world.
AB  - A unique collaboration between the Canadian Institute for Health Information
      (CIHI) and interRAI, an international research network, is supporting
      jurisdictions across Canada in collecting client-level clinical and
      administrative data for both primary and secondary uses. Standardized interRAI
      assessments, captured electronically and sent to CIHI, provide real-time decision
      support for clinicians as well as a rich longitudinal source of aggregate data
      for system planning, quality improvement and accountability. With over a million
      assessments in three CIHI-RAI data holdings, important benefits have already been
      realized at individual and organizational levels across eight Canadian
      jurisdictions. The evolution of a pan-Canadian interoperable EHR presents an
      exciting opportunity to optimize the value of these investments for the future.

PMID- 19380931
TI  - Capturing pan-Canadian Primary Health Care indicator data using multiple
      approaches for data collection.
AB  - The Canadian Institute for Health Information (CIHI), in collaboration with
      diverse stakeholders, led the development of pan-Canadian indicators to measure
      primary health care. In 2006, CIHI released a set of 105 pan-Canadian Primary
      Health Care (PHC) indicators that were developed with the assistance of national,
      provincial and territorial representatives, clinicians and researchers.
      Additionally, data gaps were identified in a series of reports. In 2006 and 2007,
      CIHI assessed options for closing the data gaps so that the indicators could be
      measured and reported. CIHI then began a program to build the data infrastructure
      needed for the PHC indicators. The program included the development of content
      standards for electronic medical records, a prototype of a voluntary reporting
      system, enhancements to surveys, and the development of reports. In 2006, fewer
      than 10% of the 105 indicators could be calculated with existing data sources.
      Now, four projects have begun and over 50% of the indicators are being captured.
      Important relationships have been established with key collaborators. These
      relationships will lead to the development of a reporting system prototype and to
      the refinement of PHC indicators and electronic medical record (EMR) content
      standards. The project for pan-Canadian PHC indicators has encouraged
      consultation and synergy. It has motivated CIHI to establish an information
      program to fill data gaps and to make PHC indicators available.

PMID- 19380932
TI  - Development of electronic medical record content standards to collect pan
      Canadian Primary Health Care indicator data.
AB  - In 2006 the Canadian Institute for Health Information (CIHI) released a set of
      105 pan-Canadian Primary Health Care (PHC) indicators. This was followed by an
      assessment of data gaps, which prevented the calculation of the indicators, and
      the data collection options available to close the gaps. A quality review of
      Electronic Medical Record (EMR) data indicated a requirement for content
      standards. In order to assist the provinces as they developed requests for
      proposal for PHC-based EMRs, the EMR content standards project was born.
      Considerable effort was made to identify standards for the Electronic Health
      Record (EHR) including existing national and international EHR content. As well,
      CIHI attempted to align the content standards with those of other projects such
      as the Physician Office System Requirements (POSR). The outcome of this project
      was a set of EMR content standards for 12 pan-Canadian PHC indicators. The
      standards will be used to develop a prototype of a PHC reporting system that
      collects and analyzes data to generate clinical quality indicators for regional
      and longitudinal comparisons. In late 2008, CIHI will release the pan-Canadian
      PHC Core Reporting Data Set. This project has developed EMR content standards to
      better understand PHC in Canada.

PMID- 19380933
TI  - Health information systems design to support a nursing model of care:
      opportunities and challenges.
AB  - The design and implementation of health information systems (HISs) in team-based
      settings is complex owing to the multiple users with different perspectives who
      interact with the system. We argue that such perspectives must be understood
      prior to designing and implementing HISs. One specific type of team-based model
      is a nursing care model. In such a model, care is provided through an
      interdisciplinary team that is lead by the nursing staff. We analyze a nursing
      based model of care according to the context of the organization, clinical unit,
      and individual as defined by the Contextual Implementation Model [1]. We then
      discuss how the nursing model will be affected by automation using different
      HISs.

PMID- 19380934
TI  - Understanding the impact on intensive care staff workflow due to the introduction
      of a critical care information system: a mixed methods research methodology.
AB  - The Intensive Care Unit (ICU) is a complex and dynamic tertiary care environment
      that requires health care providers to balance many competing tasks and
      responsibilities. Inefficient and interruption-driven workflow is believed to
      increase the likelihood of medical errors and, therefore, present a serious risk
      to patients in the ICU. The introduction of a Critical Care Information System
      (CCIS), is purported to result in fewer medical errors and better patient care by
      streamlining workflow. Little objective research, however, has investigated these
      assertions. This paper reports on the design of a research methodology to explore
      the impact of a CCIS on the workflow of Respiratory Therapists, Pediatric
      Intensivists, Nurses, and Unit Clerks in a Pediatric ICU (PICU) and a General
      Systems ICU (GSICU) in Northern Canada.

PMID- 19380935
TI  - Implementing an interdisciplinary electronic documentation system at two pilot
      units within an acute care setting.
AB  - An electronic interdisciplinary clinical documentation system that includes
      assessments and some clinical interventions was designed and implemented on two
      pilot units. This paper describes the procedures for designing the screens,
      implementing the system, and integrating the electronic documentation system with
      the workflow of nursing staff. The results of this pilot project are outlined and
      implications for future efforts are examined.

PMID- 19380936
TI  - Practical considerations for the implementation of health outcome measures.
AB  - The collection of health outcomes information is important for effective
      management of the health care system. The Health Outcomes for Better Information
      and Care (HOBIC) program is implementing a set of nurse-sensitive health outcome
      measures across the province of Ontario. This paper examines some of the
      opportunities and challenges of implementing measures across multiple
      organizations and multiple sectors of the health care system.

PMID- 19380937
TI  - Where is nursing in the electronic health care record?
AB  - The authors explore the possibilities for documenting professional nursing
      practice in an electronic health record. Recognizing that there are a variety of
      approaches to electronic documentation, the intent of this discussion is to
      generate a general rather than a particular approach to this issue. Nurses
      themselves must determine the ways in which professional nursing care will be
      captured in the electronic systems used in their facilities. Questions that arise
      from nursing include: How can nurses balance generalized care and protocol
      management with the need for documentation of each individual's nursing needs and
      particular experiences? How can the goals of nursing care be incorporated into
      the record? How can nursing actions/interventions be clearly communicated to all
      members of the health care team? In what ways can an electronic record document
      collaboration with the client to determine individualized outcomes of care and
      treatment? In considering these questions a number of issues arise: the selection
      of standardized languages to be used in the records, the title of the record, the
      tension between coding and text, the accessibility and transferability of the
      record, the ability to retrieve data on nursing outcomes through data mining
      techniques, ownership of the record, and privacy/security of the information
      stored. Although the paper will make no attempt to answer these questions it will
      draw on relevant journal articles to provide a context for this pivotal change in
      that way we account for health care practice.

PMID- 19380938
TI  - Genotypic Approaches to Therapy in Children (GATC): using information technology
      to improve drug safety.
AB  - Adverse drug reactions (ADRs) are a major cause of morbidity and mortality in
      children. Current models of ADR surveillance have repeatedly demonstrated little
      pragmatic value to practicing clinicians. ADR reporting rates in the US and
      Canada suggest that only 5% of ADRs are reported. The Genotypic Approaches to
      Therapy in Children (GATC) network was established to identify and solve drug
      safety problems in paediatrics. We hypothesized that genetic polymorphisms
      underlie a significant portion of concentration-dependent ADRs in children. Our
      objective was to establish an ADR active surveillance network in paediatric
      hospitals across Canada. Surveillance clinicians evaluate clinical information
      from ADR cases and drug-matched controls, and collected DNA samples from all
      patients. The surveillance network will enable the identification of predictive
      genomic-markers for ADRs. With this knowledge, children at risk can be identified
      before therapy is initiated and enable personalized adjustments to therapy based
      on genetic make-up.

PMID- 19380939
TI  - Overcoming the absence of tone and non-verbal elements of communication in text
      based cybercounselling.
AB  - Understanding is critical to productive interactions, good communication and
      therapeutic change. Clients may understand the meanings of words a professional
      uses but not what the professional intends. If both the client and the
      professional simply assume that the other will understand their intention because
      the words are understood, the meanings of the words may come into dispute. This,
      in turn, leads to failed communication and negative therapeutic outcomes. To
      counter this, we have developed and used the Presence Techniques in text-based
      cybercounselling for more than a decade. This paper describes these online
      counselling techniques and explores their use and effectiveness.

PMID- 19380940
TI  - A randomized clinical trial of clinical decision support in a rural community
      health network serving lower income individuals: study design and baseline
      characteristics.
AB  - Lower income individuals in the US frequently experience difficulties in
      obtaining access to needed health care services. We describe a randomized
      clinical trial that seeks to improve the quality of, and access to healthcare
      services for medically underserved populations in five rural counties of North
      Carolina. We propose to achieve these improvements by implementing system-to
      system integration via a telehealth network with an asynchronous clinical
      decision support system for health care providers.

PMID- 19380941
TI  - Patient self-management and chronic illness: evaluating outcomes and impacts of
      information technology.
AB  - Chronic illness is increasing in Australia and throughout the world. It is
      proving to be a large burden upon health systems. In response, a number of
      approaches are being tried including the introduction of self-management
      programmes to assist people in improving their health outcomes. There are also
      claims that the introduction of information and communications technology (ICT)
      tools can improve the management of these chronic conditions.This paper
      investigates the influence of ICT on the health outcomes and experiences of
      patients with chronic obstructive pulmonary disease (COPD) participating in a
      mentored self-management programme. It utilises a combined quantitative and
      qualitative methodology and introduces the use of triad interviews to provide a
      broader evaluation of the experiences of individuals within a controlled trial.
      Two sub-groups of participants within the controlled trial were examined, both
      received mentoring but one sub-group was also supported with access to an ICT
      symptom monitoring tool. This research highlights the need for more holistic
      perspectives on patients and towards the use of a variety of methodological
      approaches in designing and evaluating e-health projects. Critically, this
      research highlights the need to expand our understanding of participant's
      outcomes beyond conventional clinical or cohort based measures.

PMID- 19380942
TI  - Toyota A3 report: a tool for process improvement in healthcare.
AB  - It is proposed that the A3 problem solving process be used by hospital staff to
      improve its healthcare workflow. A hypothetical case study is given to
      demonstrate the applicability and benefits of the methodology. The research
      results show that A3 is a useful tool for healthcare organizations seeking to
      continuously improve their healthcare service quality.

PMID- 19380943
TI  - Mobile ICT support for the continuum of care.
AB  - The Wireless Wearable Physiological Monitor (WWPM) is designed to provide
      unobtrusive, regular, remote physiological monitoring of clients within their
      home environment. Its goal is to provide enough health support functions to
      enable its user to remain at home while being under a limited form of medical
      supervision. The WWPM solution will reduce the care burden on families and
      friends while providing a level of continuous care for the ill or elderly. The
      WWPM solution is a combination of non-invasive sensors that monitor a person's
      physiological data and a two-way communication system that allows the
      physiological data to be sent to a central computer application. The central
      application can interpret the data received and automatically prompt the client
      to take appropriate action or alert a care provider who can intervene with the
      needed support. The central application is intended for use by care providers
      within the traditional continuum, that is, as a component in a patient's health
      management or care plan. It is this combination of data, professional care and
      communication that will produce the medical and behavioral outcomes necessary for
      individuals to manage their health outside of traditional health service
      institutions.

PMID- 19380944
TI  - An EHR-based paradigm shift in the operation of mental health and addiction
      services.
AB  - This paper responds to a commonly expressed belief, or perhaps hope, that full
      implementation of the electronic health record (EHR) will promote a "paradigm
      shift" in the delivery of health services, enhancing both service system
      efficiency and effectiveness in ways that would not have otherwise been possible.
      A model is proposed that defines stages in the development of the EHR in terms of
      two sets of functional components: 1) information management tools used to
      support the delivery of care; and 2) decision support tools that use information
      drawn from the EHR to promote functional integration among the components of
      complex service systems. "Paradigm shift" is defined operationally within this
      framework in terms of evolution of the EHR through these stages. The concept of
      "clinical interoperability" (anchored in a semantically interoperable EHR) is
      elaborated upon and presented as the sine qua non for a distinctive form of
      paradigm change that centres on support for care delivery within any given
      location in the system, and on EHR-based support for client movement through the
      system. The Vancouver Island Health Authority/Infoway Bridges, now deployed
      across the full array of hospital and community-based mental health and addiction
      services, is an example of an EHR that leverages the semantically interoperable
      components of an EHR to support a paradigm shift in clinical interoperability for
      the mental health and addictions service system.

PMID- 19380945
TI  - Potential Return on Investment (RoI) on web-based diabetes education in UK.
AB  - The incidence of diabetes mellitus is growing in the UK. As most diabetes care is
      performed by the patients themselves, structured education is one way to
      encourage their responsible participation in delivering effective care.
      Continuous e-learning by Internet has proven to be a useful method of diabetes
      education. "Return on Investment" (RoI) can be used as an indicator of the cost
      benefit of web-based education. RoI is the ratio of money gained or lost on an
      investment relative to the amount of money invested. This report uses system
      dynamics modeling to predict the flow of patients in the educational system and
      the cost of their care. The analysis compared traditional and web-based
      education. Separate models were developed for each educational method and
      simulated until 2020 in one year intervals. The population of diabetic patients
      was adjusted at each cycle according to anticipated incidence and mortality
      rates. The population of educated diabetic patients was based on the educational
      capacity and literacy limits of each method. A report by the National Health
      Service (NHS) was used to calculate the cost of care by considering the cost
      difference between uneducated and educated patients. By 2020 with an annual rate
      of inflation of 3%, the annual cost of care is projected to increase to pound
      3.67 billion for the traditional model as compared to pound 3.39 billion for the
      web-based model. RoI is estimated to be a ratio of 32.33. Investment in web-based
      diabetes education is not only a health benefit but also a reduction in care
      cost.

PMID- 19380946
TI  - Breaking barriers to self-management of chronic diseases - the MaXi project.
AB  - The purpose of this study is to establish a foundation for participatory design
      between Information Technology (IT) professionals and people with chronic
      diseases resulting in IT-supported compensation in daily life. The paper presents
      the methods applied and results from a qualitative study to understand everyday
      life with diabetes. The participants are 8 families with one or more diabetic
      member. Our analysis outlines perspectives, activities, locations and information
      related to daily life with diabetes. On the basis of the analysis a number of
      artifacts are designed and tested in a living lab environment in Skagen, Denmark.
      It is concluded that participatory design and the use of the living lab concept
      yielded a richness of data adequate for iterative design cycles.

PMID- 19380947
TI  - Preventing technology-induced errors in healthcare: the role of simulation.
AB  - We describe a novel approach to the study and prediction of technology-induced
      error in healthcare. The objective of our approach is to identify and reduce the
      potential for error so that the benefits of introducing information technology,
      such as Computerized Physician Order Entry (CPOE) or Electronic Health Records
      (EHRs), are maximized. The approach involves four phases. In Phase 1, we
      typically conduct small scale clinical simulations to assess whether or not the
      use of a new information technology can introduce error. (Human subjects are
      involved and user-system interactions are recorded.) In Phase 2, we analyze the
      results from Phase 1 to identify statistically significant relationships between
      usability issues and the occurrence of error (e.g., medication error). In Phase
      3, we enter the results from Phase 2 into computer-based simulation models to
      explore the potential impact of the technology over time and across user
      populations. In Phase 4, we conduct naturalistic studies to examine whether or
      not the predictions made in Phases 2 and 3 apply to the real world. In closing,
      we discuss how the approach can be used to increase the safety of health
      information systems.

PMID- 19380948
TI  - Exploring the relationship between training and usability: a study of the impact
      of usability testing on improving training and system deployment.
AB  - The relationship between usability and training remains to be explored in health
      informatics. We examine the training given during the implementation of an
      institutional electronic medical record system, as well as the usability of the
      system from the perspective of new users who have been recently trained. We
      examine in which ways video-based usability testing with new users, who received
      classroom training one month earlier, can be used to a) indicate needed changes
      in the training program, and b) provide feedback to improve system customization
      and deployment. Usability testing methods were found to be an important adjunct
      to system deployment: they can improve the system implementation as well as
      suggest strategies for user education.

PMID- 19380949
TI  - Scenario-based testing of health information systems (HIS) in electronic and
      hybrid environments.
AB  - Researchers have identified sources of technology-induced errors involving health
      information systems (HIS) across the software development lifecycle. In this
      paper the authors review approaches to identifying technology-induced error and
      describe, compare and contrast the advantages and disadvantages of using
      predictive and post-implementation methodologies to identify technology-induced
      error. Following this, the authors focus upon clinical simulations using scenario
      based testing as a methodology for diagnosing technology-induced errors to assess
      HIS ability to respond to the stresses and strains of health professionals using
      such systems in real-world clinical settings.

PMID- 19380950
TI  - Security evaluation and assurance of electronic health records.
AB  - Electronic Health Records (EHRs) maintain information of sensitive nature.
      Security requirements in this context are typically multilateral, encompassing
      the viewpoints of multiple stakeholders. Two main research questions arise from a
      security assurance point of view, namely how to demonstrate the internal
      correctness of EHRs and how to demonstrate their conformance in relation to
      multilateral security regulations. The above notions of correctness and
      conformance directly relate to the general concept of system verification, which
      asks the question "are we building the system right?" This should not be confused
      with the concept of system validation, which asks the question "are we building
      the right system?" Much of the research in the medical informatics community has
      been concerned with the latter aspect (validation). However, trustworthy security
      requires assurances that standards are followed and specifications are met. The
      objective of this paper is to contribute to filling this gap. We give an
      introduction to fundamentals of security assurance, summarize current assurance
      standards, and report on experiences with using security assurance methodology
      applied to the EHR domain, specifically focusing on case studies in the Canadian
      context.

PMID- 19380951
TI  - Using heuristic evaluations to assess the safety of health information systems.
AB  - Health information systems (HISs) are typically seen as a mechanism for reducing
      medical errors. There is, however, evidence to prove that technology may actually
      be the cause of errors. As a result, it is crucial to fully test any system prior
      to its implementation. At present, evidence-based evaluation heuristics do not
      exist for assessing aspects of interface design that lead to medical errors. A
      three phase study was conducted to develop evidence-based heuristics for
      evaluating interfaces. Phase 1 consisted of a systematic review of the
      literature. In Phase 2 a comprehensive list of 33 evaluation heuristics was
      developed based on the review that could be used to test for potential technology
      induced errors. Phase 3 involved applying these healthcare specific heuristics to
      evaluate a HIS.

PMID- 19380952
TI  - Televaluation and usability assessment of the human-machine interface for a novel
      adaptive health knowledge translation system.
AB  - We describe results from usability assessment of a novel adaptive health
      knowledge translation system interface. Search or retrieval logic, navigation,
      and presentation elements are crucial to delivering best content. Design
      requirements have been enhanced by assessing participant needs and desired
      features.

PMID- 19380953
TI  - Assessing software impact on clinical workflow and resource utilization.
AB  - A usability study is described that compares a web-based capecitabine-prescribing
      and dispensing application to traditional manual methods. The behaviours of two
      small groups, oncologists and pharmacists, were recorded and analyzed using a
      case study of patient with metastatic colon cancer. The study indicated for the
      oncologists that workflow and resource utilization decreased due to the
      application, however, for the pharmacists the results were less positive. This
      type of case study simulation can be used to determine the impact of software
      applications on their users.

PMID- 19380954
TI  - Architectural and usability considerations in the development of a Web 2.0-based
      EHR.
AB  - In our previous work, we described an electronic health record (EHR) architecture
      based on Web 2.0 principles. With this architecture, users in healthcare and
      public health can select, configure, share and control the information and
      interfaces they use by means of simple techniques such as "drag-and-drop" without
      the intervention of programmers. We extend this work by discussing architectural
      and usability considerations important for creating such an EHR. These include:
      new affordances facilitating element creation, responsiveness while using rich
      client-side interaction, consistency versus flexibility, security, workflow and
      evaluation.

PMID- 19380955
TI  - Comparative study of heuristic evaluation and usability testing methods.
AB  - Usability methods, such as heuristic evaluation, cognitive walk-throughs and user
      testing, are increasingly used to evaluate and improve the design of clinical
      software applications. There is still some uncertainty, however, as to how those
      methods can be used to support the development process and evaluation in the most
      meaningful manner. In this study, we compared the results of a heuristic
      evaluation with those of formal user tests in order to determine which usability
      problems were detected by both methods. We conducted heuristic evaluation and
      usability testing on four major commercial dental computer-based patient records
      (CPRs), which together cover 80% of the market for chairside computer systems
      among general dentists. Both methods yielded strong evidence that the dental CPRs
      have significant usability problems. An average of 50% of empirically-determined
      usability problems were identified by the preceding heuristic evaluation. Some
      statements of heuristic violations were specific enough to precisely identify the
      actual usability problem that study participants encountered. Other violations
      were less specific, but still manifested themselves in usability problems and
      poor task outcomes. In this study, heuristic evaluation identified a significant
      portion of problems found during usability testing. While we make no assumptions
      about the generalizability of the results to other domains and software systems,
      heuristic evaluation may, under certain circumstances, be a useful tool to
      determine design problems early in the development cycle.

PMID- 19380956
TI  - The user-centered approach in the development of a complex hospital-at-home
      intervention.
AB  - We discuss the development of a comprehensive remote patient monitoring system
      that facilitates the self-care of patients undergoing nocturnal home hemodialysis
      (NHHD), a complex hospital-at-home therapy. The use of a continuous, iterative
      approach with user involvement for the validation of assumptions can avoid
      situations where the system serves a patient poorly. An ethnographic analysis was
      used to determine specific design principles, which were reviewed with the
      patients prior to development of the system. Iterative designs were tested
      through usability testing and further validation was done with a member-checking
      exercise. Patients expressed concern about the physical obtrusiveness of
      monitoring which, consequently, led to a lack of adherence. The need for
      monitoring the integrity of the bloodlines was identified as important because
      one of the most significant fears among patients was potential blood loss.
      Patients expressed a need for immediate human intervention in response to an
      alert. The use of ethnography, usability testing, and member-checking methods in
      a user-centered approach to design can result in systems that better meet the
      needs of the patients and caregivers alike.

PMID- 19380957
TI  - Applying a Human Factors Engineering approach to healthcare IT applications:
      example of a medication CPOE project.
AB  - This paper describes a Human Factors Engineering approach to a medication use
      system in the context of a hospital medication CPOE project. It presents the
      results obtained from the organizational analysis and describes the variations in
      the distribution of tasks among actors in the medication use process, which
      depend on the organization of the work system. It then focuses on nurses'
      medication administration tasks including the preparation and update of pill
      dispensers. This situation may be characterized according to the distributed
      cognition framework. The high level organizational features have an impact on the
      quality and safety of the coordination and communication procedures that
      characterize medication preparation and administration by nurses.

PMID- 19380958
TI  - Adopting and introducing new technology to improve patient care: a wedding of
      clinicians and informatics specialists.
AB  - The BC Cancer Agency sees 128,172 patients per year, of which 2,186 are referred
      to the Patient Symptom Management/Palliative Care (PSMPC) clinics for tertiary
      symptom management. Other than at the PSMPC clinics, screening for symptom
      distress is extremely variable because there is no systematic assessment
      protocol. In a recent audit of patients coming to the Cancer Agency,
      approximately 64% of patients reported experiencing a moderate to severe level of
      symptom distress. Of the total patients in the audit (n = 1,147), only 18 were
      seen by the PSMPC teams and it is unclear whether or not the remaining patients
      had their symptoms attended to by a health professional at the BCCA.The tool
      which the BCCA has chosen for screening and assessment is the Edmonton Symptom
      Assessment System (ESAS), which was developed by Dr. Eduardo Bruera. ESAS is a
      nine-item, self-reporting, visual analogue instrument used to measure pain and
      other symptoms using numeric ratings. Cancer Care Ontario (CCO) has developed an
      electronic means whereby patients' ESAS scores are entered and housed in an
      electronic health record and then used for triage. BCCA is in partnership with
      CCO to adapt this system for use in BC.

PMID- 19380959
TI  - Designing technology to support end of life decision making.
AB  - Despite being in existence for more than 15 years, the effectiveness of advanced
      directives has yet to be established. One possible reason for this is an
      inadequate level of shared understanding among stakeholders - the dying patient,
      family members and medical practitioners - regarding values and their
      implications for future actions at the end-of-life. Americans find it difficult
      and stressful to discuss death. This research investigates whether the
      articulation and alignment of values and meanings for the end of life can be
      promoted by framing them as acts of negotiation. This research uses
      ethnomethodology to examine the needs of this population, followed by grounded
      theory analysis of the interview data. The author concludes with three design
      guidelines for designing technology to aid in the exploration of options at the
      end of life.

PMID- 19380960
TI  - Structured data system for a breast cancer medical record.
AB  - We have developed software for an Electronic Medical Record (EMR) to be used by
      oncologists and researchers. It has rapid, structured data entry, visualization
      of clinical information and a searchable data base. Interactive, rules-based
      forms were designed for structured data entry. The web-based forms have been
      customized for the clinical staff who enter the data. The forms have been tested
      by oncologists and their office assistants. Modules have been added to upload
      images and add legends, metadata, and code classifications such as ICD and CPT.
      Other features include a search interface and a permission system that controls
      user access. Oncologists enter detailed information during a patient's visit to
      the clinic. The electronic forms capture diagnoses, stage and history, which
      includes social, family, and medical history. A time map provides a graphical
      summary of a patient's record. Visualization of complex clinical information with
      intuitive navigation increases clarity while retaining the detail necessary for
      clinical information. Customized data entry forms and automatic coding speed the
      workflow. The system can potentially interface with multi-institutional data
      sharing systems such as Cancer Bioinformatics Grid (CaBig).

PMID- 19380961
TI  - The eFOSTr PROJECT: design, implementation and evaluation of a web-based Personal
      Health Record to support health professionals and families of children undergoing
      transplants.
AB  - We describe the eFOSTr PROJECT, which has involved the design, implementation and
      testing of a unique Internet-based Personal Health Record (PHR) to support the
      families of transplant children and their healthcare providers. There are many
      gaps in the way that information is stored for children undergoing or about to
      undergo transplants. This group of children presents the most challenging
      exercise in information support between geographic and institutionally separated
      medical teams. They are, however, supported by highly motivated parents and
      families in life-threatening circumstances. A PHR was designed that allows for
      secure data entry, data storage, and easy controlled data access by the
      children's guardians or parents. The record includes contact and team member
      names, and medical data such as growth charts, immunizations, allergies,
      medications, lab values and scanned or digitized medical reports. Families can
      record the progress of their child as they would with a paper binder and
      customize their child's record with a photograph gallery and Internet link
      section for personal and general interest. Extensive computer-based testing of
      the PHR is complete. The system is being evaluated to determine the extent to
      which it meets the information needs of families and health providers in
      differing situations across Canada. The effectiveness of the system as a means
      for providing continuity of information and education is also being assessed. To
      conduct these evaluations, new users are being interviewed and tracked in a
      qualitative longitudinal study. Characteristics of the needs of the transplant
      families known to the David Foster Foundation (DFF) in Canada are described so
      that comparisons can be made to other patient groups who could benefit from their
      own adapted and specialized PHRs.

PMID- 19380962
TI  - A comprehensive infectious disease management system.
AB  - An efficient electronic management system is now an essential tool for the
      successful management and monitoring of those affected by communicable infectious
      diseases (Human Immunodeficiency Virus - HIV, hepatitis C - HEP C) during the
      course of the treatment. The current methods which depend heavily on manual
      collecting, compiling and disseminating treatment information are labor-intensive
      and time consuming. Clinics specialized in the treatment of infectious diseases
      use a mix of electronic systems that fail to interact with each other, result in
      data duplication, and do not support treatment of the patient as a whole. The
      purpose of the Infectious Disease Management System is to reduce the
      administrative overhead associated with data collection and analysis while
      providing correlation abilities and decision support in accordance with defined
      treatment guidelines. This Infectious Disease Management System was developed to:
      Ensure cost effectiveness by means of low software licensing costs, Introduce a
      centralized mechanism of collecting and monitoring all infectious disease
      management data, Automate electronic retrieval of laboratory findings, Introduce
      a decision support mechanism as per treatment guidelines, Seamlessly integrate of
      application modules, Provide comprehensive reporting capabilities, Maintain a
      high level of user friendliness.

PMID- 19380963
TI  - Application of House of Quality (HOQ) to health care management.
AB  - The House of Quality (HOQ) model is proposed to improve health care quality
      control. A hypothetical case study is given to demonstrate the applicability and
      benefits of using the proposed methodology. The benefit and drawback analysis of
      HOQ are also addressed. Concluding remarks and proposals for further research are
      presented at the end of this paper.

PMID- 19380964
TI  - Selecting electronic health record systems: development of a framework for
      testing candidate systems.
AB  - The process of selecting electronic health record systems is one of the most
      critical decisions in the journey towards automating and improving healthcare
      using information technology. However, there are a wide variety of problems
      associated with system selection and procurement processes in healthcare. Indeed
      the literature contains numerous examples of systems that were purchased and
      customized that failed to meet user needs, were implemented well behind schedule,
      which cost much more than expected and which in some cases failed completely. In
      this paper we describe a framework which we have developed and have begun to
      apply in considering key processes in the selection of electronic health records 
      i.e. the testing of potential candidate systems to determine if they meet user
      and institutional needs. The objective of our work is to improve our
      understanding of and the effectiveness of this critical decision making aspect of
      health informatics. In our work we consider system selection in terms of strength
      of evidence obtained from testing candidate systems.

PMID- 19380965
TI  - Getting to 100%: a framework to define and reach target order entry rates.
AB  - Following a detailed review of orders entered into a clinical information system,
      we propose a framework to define computerized physician order entry types and a
      more useful formula for calculating order entry rate.

PMID- 19380966
TI  - Evolution of a national approach to evaluating the benefits of the electronic
      health record.
AB  - Demonstrating the value of eHealth investments to users and other stakeholders,
      and driving ongoing optimization of benefits are increasingly important
      components of eHealth implementations in Canada. For these reasons, Canada Health
      Infoway is working with provincial partners to make research and evaluation an
      important component in Electronic Health Record (EHR) investments. Leading
      provinces working with Infoway, including British Columbia, the Province of
      Quebec, and Newfoundland and Labrador, are making evaluation a central part of
      their eHealth strategies and using evaluation results to optimize the benefits of
      investments. We provide an overview of benefits evaluation strategies and lessons
      learned. Examples of early evaluations completed and those currently underway
      provide insights into the challenges and benefits of investments in EHR.

PMID- 19380967
TI  - "Physicians' Adoption Score" - physicians are not a homogenous group.
AB  - The issue of "Physicians' Adoption" is one of the big challenges facing wide
      scale implementation of electronic health records (EHRs). An important question
      is why the number of physicians using EHRs in their practice has not reached the
      level expected. While this issue has been addressed widely in the literature, the
      term "physicians" is used generally to encompass a broad range of roles and
      responsibilities. Physicians are not a homogeneous group and, without a good
      understanding of the differences among physicians, it is not logical or feasible
      to come up with a universal blue print devised to convince all physicians to
      accept an EHR implementation in their practices. First we discuss the barriers to
      implementing an EHR based on the characteristics of different types of physicians
      and then introduce an "Adoption Score" for physicians and provide a tool to
      measure the barriers. We discuss the importance of this scoring system and how
      similar methods can be helpful to assign an adoption score at an organizational
      level.

PMID- 19380968
TI  - The development of a risk identification screening framework for healthcare
      information systems.
AB  - Health information systems are costly, especially when they are not used or when
      they impede workflow. Risk assessment is used to identify and remedy problem
      areas so that systems are safe. While there are discussions of design project
      risk management, for example, see McConnell [1], there is little information
      about screening the fit of a system with respect to its users, the task and the
      healthcare organization. Such analyses could be important in improving the fit of
      information systems in healthcare, thereby decreasing risk of system and project
      failure. A risk-screening framework for health informatics is presented.

PMID- 19380969
TI  - Extending the infoway benefits evaluation framework for health information
      systems.
AB  - A proposal is made that extends the current Canada Health Infoway Benefits
      Evaluation (BE) Framework for Health Information Systems (HIS) being deployed in
      Canada. The current BE framework takes a micro view of HIS quality, use and
      impact at the local level whereas the extended framework takes into account the
      broader socio-organizational and contextual aspects known as the meso and macro
      views of HIS deployment. The meso view addresses the people, organization,
      network and implementation dimensions. The macro view focuses on the contextual
      dimensions of technology standard, funding/incentive, legislation/policy and
      professional practice. Validation of this extended BE framework is being planned
      through a comparative review of recent HIS evaluation literature, a Delphi
      consensus process with HIS experts and users, and multiple validation studies
      with recent HIS implementation projects in British Columbia.

PMID- 19380970
TI  - eDoc evaluation - at eighteen months into the challenge.
AB  - We describe an evaluation plan for electronic clinical documentation. Guided by
      Canada Health Infoway Benefits Evaluation Framework, the evaluation was performed
      across a single organization with four health care sites and included reviews of
      documentation practices from the nursing and health disciplines. Data collection
      methods included chart audits, shadowing, surveys and focus group meetings. Key
      recommendations drawn from the data analysis will help to guide documentation
      format and practice improvements.

PMID- 19380971
TI  - Strategies to increase familiarization and acceptance of electronic health
      records among health professionals and consumers.
AB  - There are many reasons an organization may choose to implement electronic health
      records. The challenge is to acknowledge the benefits and deficiencies of the
      electronic health record, to understand the driving forces for implementation and
      the barriers to it, and to effect change in the workplace and consumer behaviour.
      Indeed, one challenge is the determination of the organizational stance with
      regard to these factors. If all of these factors are seriously considered and the
      risks to implementation measured, a successful implementation should ensue.

PMID- 19380972
TI  - IT for advanced life support in hospitals.
AB  - In this study we analyzed how IT support can be established for the treatment and
      documentation of advanced life support (ALS) in a hospital. In close
      collaboration with clinical researchers, a running prototype of an IT solution to
      support the clinical decisions in ALS was developed and tried out in a full scale
      simulation environment. We have named this IT solution the CardioData Prototype.

PMID- 19380973
TI  - Effective solutions in introducing Server-Based Computing into a hospital
      information system.
AB  - Server-Based Computing (SBC) is a technology for terminal administration that
      achieves higher security at lower expense. Use of SBC in large hospitals,
      however, is not widespread because methods to effectively implement the
      technology have not been fully established. We present a system design that uses
      SBC in a large-scale hospital and then discuss the implementation problems and
      their solutions. With the exception of network traffic estimates, the server size
      estimates were validated. Three results from an evaluation of an SBC
      implementation were: 1) security was re-enforced by applying multiple-policy
      adaptation to a single client terminal, 2) cost reduction was realized by having
      fewer PC failures and a lower power consumption, and 3) user-roaming was found to
      be effective in reducing the number of iterative operations performed by users.

PMID- 19380974
TI  - Applying natural language processing toolkits to electronic health records - an
      experience report.
AB  - A natural language challenge devised by Informatics for Integrating Biology and
      the Bedside (i2b2) was to analyze free-text health data to construct a multi
      class, multi-label classification system focused on obesity and its co
      morbidities. This report presents a case study in which a natural language
      processing (NLP) toolkit, called NLTK, was used in the challenge. This report
      provides a brief review of NLP in the context of EHR applications, briefly
      surveys and contrasts some existing NLP toolkits, and reports on our experiences
      with the i2b2 case study. Our efforts uncovered issues including the lack of
      human annotated physician notes for use as NLP training data, differences between
      conventional free-text and medical notes, and potential hardware and software
      limitations affecting future projects.

PMID- 19380975
TI  - Improving the efficiency and accuracy of a tablet PC interface for computerized
      provider order entry through usability evaluation and provision of data entry
      strategies.
AB  - Six nurses participated in usability testing sessions during which they entered
      35 physician orders using a tablet PC. Their performance was recorded and then
      replayed to code the user and system behaviours associated with order entry.
      Results indicate that problematic user navigational and data entry behaviours
      occur more frequently than system related behaviours but that the latter are
      associated with much higher error rates. Field-specific data entry strategies
      introduced during user training were adopted 77.6% of the time and resulted in
      improved efficiency.

PMID- 19380976
TI  - Mobile phones as mediators of health behavior change in cardiovascular disease in
      developing countries.
AB  - The global burden of cardiovascular diseases (CVD) is becoming a growing problem
      in developing countries. Successful self-management of CVD is dependent on a
      multitude of factors, including social support, communication with health care
      providers, careful monitoring, and other determinants. The growing market
      penetration and the communication properties of mobile phones create
      opportunities for innovation in promoting CVD self-management through support of
      lifestyle and behavior modification. Mobile phones support various modes of
      communication and interaction, have fewer adoption barriers, and are more
      prevalent than other available technologies in developing countries. However,
      mobile phone interventions are not without many challenges such as mobile
      infrastructure, electric infrastructure, access to mobile devices, and
      appropriate user interfaces for interaction. In this paper, we discuss current
      evidence as well as research opportunities to explore the role of mobile phones
      in supporting behavior modification in developing countries.

PMID- 19380977
TI  - Ongoing evaluation of ease-of-use and usefulness of wireless tablet computers
      within an ambulatory care unit.
AB  - This ongoing research is to assess user acceptance of wireless convertible tablet
      portable computers in their support of patient care within the clinic environment
      and to determine their impact on workload reduction for the information staff. A
      previous publication described our initial experience with a limited wireless
      environment. There, we tested the premise that wireless convertible tablet
      computers were equivalent to desktop computers in their support of user tasks.
      Feedback from users demonstrated that convertible tablet computers were not able
      to replace desktop computers. Poor network access was a weakness as well as the
      "cognitive overhead" encountered due to technical problems. This paper describes
      our further experience with a centre-wide wireless implementation while using a
      new wireless device. The new tablets, which have some unique functions that
      existing desktop computers do not provide, have been well received by the
      clinicians.

PMID- 19380978
TI  - Telematics in acute trauma care.
AB  - Each year, 20,000 people in Germany die because of a traffic accident.
      Altogether, yearly productivity loss caused by these injuries is estimated to be
      around 5 billion Euros. International and national studies revealed the trauma
      center level of the primary hospital as the major predictor for trauma related
      mortality. In 2006 the German Society for Trauma Surgery (DGU) called its members
      to form regionally based networks for the exchange of data among hospitals
      engaged in trauma care. In April 2008 the north-west region of Germany with 49
      hospitals, three hospitals in the Netherlands, and local emergency services
      founded the "TraumaNetwork NorthWest (TNNW). The major goals of the TNNW are: 1)
      to shorten the time between accident and admission to the appropriate hospital,
      2) to create effective means of communication, and 3) to implement common pre-
      and in-hospital standards for trauma care. Since the needed application software
      is not commercially available, a team of computer and medical specialists has
      been formed for its development. Once the software is in place, a pre- and post
      analysis will be performed to study the consequences of the application on
      transportation time and injury-related mortality within the region. The project
      is recognized as a pilot project by the DGU and if it is successful is meant to
      be adapted across Germany.

PMID- 19380979
TI  - Innovation in the North: are health service providers ready for the uptake of an
      internet-based chronic disease management platform?
AB  - Remote and rural regions in Canada are faced with unique challenges in the
      delivery of primary health services. The purpose of this study was to understand
      how patients and healthcare professionals in northern British Columbia might make
      use of the Internet to manage cardiovascular diseases. The study used a
      qualitative methodology. Eighteen health professionals and 6 patients were
      recruited for a semi-structured interview that explored their experience in
      managing patients with cardiovascular disease and their opinions and preferences
      about the use of the Internet in chronic disease management. Key findings from
      the data suggest that a) use of the Internet helps to maintain continuity of care
      while a patient moves through various stages of care, b) the Internet may
      possibly be used as an educational tool in chronic disease self-management, c)
      there is a need for policy development to support Internet-based consultation
      processes, and d) while health providers endorse the notion of electronic
      advancement in their practice, the need for secure and stable electronic systems
      is essential.

PMID- 19380980
TI  - Telehealth-based framework for supporting the treatment of obstructive sleep
      apnea.
AB  - We describe an application of a computer-based system and telehealth approach for
      support of the continuous positive airway pressure (CPAP) treatment for
      obstructive sleep apnea (OSA). A conceptual framework is introduced that has four
      major components: patients' education and communication, measurement of patients'
      adherence, CPAP unit test, and CPAP treatment evaluation. The measurement and
      evaluation processes are based on a fuzzy logic approach and they use a set of
      predefined fuzzy rules. The rules are utilized for the calculation of patient's
      adherence and treatment effectiveness using patients' records, self-reported
      adherence data, and automatically downloaded data from the CPAP machines.
      Further, we discuss the need for a telehealth support system for OSA patients in
      the rural communities and small cities of British Columbia.

PMID- 19380981
TI  - Optimizing standard patient management through order sets - impact on care (blood
      cultures).
AB  - We show that order set design and support must be thoughtful to result in
      improved quality of care and reduced waste and that order set use should be
      monitored to confirm expected impact and detect unanticipated consequences.

PMID- 19380982
TI  - Use of case mix tools for utilization management and planning.
AB  - An aging population, new technologies and drugs, and tightening constraints on
      financial and human resources have placed increased demands on hospitals to meet
      health care needs. Canadian hospitals, health regions, and ministries are placing
      a high priority on the evaluation of appropriateness and efficiency of medical
      care and on the proactive and targeted reduction of inefficiencies. The CMG+
      grouping methodology is a case mix tool produced by the Canadian Institute for
      Health Information (CIHI) to analyze the acute-care inpatient population in
      Canada. CMG+ methodology can be applied, for example, to utilization management.
      The expected length of stay (ELOS) indicator can be used as a benchmark for
      assessing the length-of-stay distribution of various subgroups of patient
      activity. It can also be used to compute potentially conservable days and to
      identify those patient subgroups where gains in efficiency may be realized. We
      describe CMG+ utilization management using this and other examples.

PMID- 19380983
TI  - A standard operating protocol (SOP) and minimum data set (MDS) for nursing and
      medical handover: considerations for flexible standardization in developing
      electronic tools.
AB  - As part of Australia's participation in the World Health Organization, the
      Australian Commission on Safety and Quality in Health Care (ACSQHC) is the
      leading federal government technical agency involved in the area of clinical
      handover improvement. The ACSQHC has funded a range of handover improvement
      projects in Australia including one at the Royal Hobart Hospital (RHH), Tasmania.
      The RHH project aims to investigate the potential for generalizable and
      transferable clinical handover solutions throughout the medical and nursing
      disciplines. More specifically, this project produced an over-arching minimum
      data set (MDS) and over-arching standardized operating protocol (SOP) based on
      research work on nursing and medical shift-to-shift clinical handover in general
      medicine, general surgery and emergency medicine. The over-arching MDS consists
      of five headings: situational awareness, patient identification, history and
      information, responsibility and tasks and accountability. The over-arching SOP
      has five phases: preparation; design; implementation; evaluation; and
      maintenance. This paper provides an overview of the project and the approach
      taken. It considers the implications of these standardized operating protocols
      and minimum data sets for developing electronic clinical handover support tools.
      Significantly, the paper highlights a human-centred design approach that actively
      involves medical and nursing staff in data collection, analysis, interpretation,
      and systems design. This approach reveals the dangers of info-centrism when
      considering electronic tools, as information emerges as the only factor amongst
      many others that influence the efficiency and effectiveness of clinical handover.

PMID- 19380984
TI  - Managing terminology assets in Electronic Health Records.
AB  - Electronic Health Record (EHR)systems rely on standard terminologies and
      classification systems that require both Information Technology (IT) and
      Information Management (IM) skills. Convergence of perspectives is necessary for
      effective terminology asset management including evaluation for use, maintenance
      and intersection with software applications. Multiple terminologies are necessary
      for patient care communication and data capture within EHRs and other information
      management tasks. Terminology asset management encompasses workflow and
      operational context as well as IT specifications and software application run
      time requirements. This paper identifies the tasks, skills and collaboration of
      IM and IT approaches for terminology asset management.

PMID- 19380985
TI  - Normalization of reported lab results.
AB  - It is possible for physicians to review electronic lab results in the format of
      the sending lab and, as well, to see them using advanced visualization
      techniques. When lab results for a particular patient are reviewed by a
      physician, they must be integrated with other lab results and other issues of the
      patient. Viewing the results can present a number of difficulties. One problem
      relates to normal ranges that can change over time and can be different when sent
      by different labs. This is not an issue when results are printed but when the
      results are graphed with their normal range displayed, distortions often prompt
      questions from patients who are shown the results. There are also situations were
      it is important to review a cluster of four or five different tests to properly
      understand the clinical situation. Tests in the cluster, however, can have
      interrelated result values that differ by orders of magnitude. Normalization,
      which can be used to scale the graphs, has been proposed in the past but not
      gained any popularity. The benefits of this approach are discussed.

PMID- 19380986
TI  - Medical text analytics tools for search and classification.
AB  - A text-analytic tool has been developed that accepts clinical medical data as
      input in order to produce patient details. The integrated tool has the following
      four characteristics. 1) It has a graphical user interface. 2) It has a free-text
      search tool that is designed to retrieve records using keywords such as "MI" for
      myocardial infarction. The result set is a display of those sentences in the
      medical records that contain the keywords. 3) It has three tools to classify
      patients based on the likelihood of being diagnosed for myocardial infarction,
      hypertension, or their smoking status. 4) A summary is generated for each patient
      selected. Large medical data sets provided by the Institute for Clinical
      Evaluative Sciences were used during the project.

PMID- 19380987
TI  - Evaluating the effectiveness of modeling principles for data models.
AB  - We evaluated the effectiveness of modeling principles intended to harmonize the
      information representation between terminology-ontology models and information
      models. Our study utilized dental clinical statements and sample dental record
      questions. We asked experts to define the equivalency (mapping) of these elements
      and measured their agreement. We modified the data elements and asked the experts
      to conduct subsequent mappings. We measured the agreement and compared the levels
      of agreement before and after changes, expecting that agreement would increase.
      The level of agreement (Kappa) before modeling was 0.3 to 0.4 and after was 0.5
      (p<0.05). The difference was small but statistically significant. Our results
      suggest that the modeling principles improve information representation since
      agreement increased.

PMID- 19380988
TI  - Boundary objects in the multidisciplinary care management of chronic conditions:
      multiple chemical sensitivity.
AB  - Chronic conditions such as Multiple Chemical Sensitivity (MCS) are a significant
      challenge to the health care system as they are poorly understood, poorly
      documented and lack accepted or standardized treatment strategies. Research has
      shown that the successful management of patients with such conditions requires a
      multidisciplinary team of clinicians and the comprehensive assessment of factors
      contributing to the ill health. Results from two studies that have shown
      reduction in health care costs and improvement in symptoms for patients with MCS
      are presented. We explore the use of a controlled clinical vocabulary as a
      boundary object in care documents to facilitate collaborative management of
      patients with MCS.

PMID- 19380989
TI  - Control of membrane fouling in membrane bioreactor process by coagulant addition.
AB  - The control of membrane fouling is an essential issue in membrane bioreactor
      (MBR) process. It has been recognized that the most important factors that affect
      membrane fouling are presence of soluble microbial products (SMP) and
      extracellular polymeric substances (EPS) in a reactor. The objective of this
      study was to examine the effect of the coagulant addition on the membrane fouling
      in the MBR process. Accordingly, laboratory scale batch experiments and MBR
      experiments were conducted using coagulant. In batch experiments, effective SMP
      removal and control of EPS release were observed by coagulant addition. Fe
      coagulant was slightly more effective than Al coagulant in the addition of same
      mole amount. Therefore, Fe was used as coagulant in MBR experiments. In MBR
      experiments, Fe solutions of 0 mg/L, 2,260 mg/L and 4,520 mg/L were added into
      the tanks (Run1, Run2 and Run3, respectively) with the flow rate of 200 mL/d. COD
      removal efficiencies of 97% and phosphorus removal efficiencies of 92% were
      observed by Fe addition in the MBR experiment. Membrane fouling occurred more
      often in Run1 than in the other two Runs. Membrane was cleaned 18, 9 and 5 times
      in Run1, Run2 and Run3, respectively during 40 days runs. This suggested that the
      membrane fouling was reduced by the coagulant addition. The protein and
      carbohydrate concentrations of the SMP in the fraction of 1 microm-0.4 microm in
      Run2 and Run3 were significantly lower than that in Run1 and the particle size of
      the activated sludge was obviously increased in Run2 and Run3. These results
      suggested that the coagulant addition is effective to control the membrane
      fouling.

PMID- 19380990
TI  - Measuring odour emission and biofilter efficiency in composting plants by proton
      transfer reaction-mass spectrometry.
AB  - PTR-MS (Proton Transfer Reaction-Mass Spectrometry) is an innovative technique
      that allows the rapid detection of most volatile organic compounds (VOCs) with
      high sensitivity (sub-ppb) and by direct injection. We describe here the possible
      use of PTR-MS in waste managements and composting plants both for the real time
      monitoring of volatile emissions and, after calibration with olfactometric
      assessments, for the instrumental determination of odour concentration. Beside a
      short description of the technique, we will report on the calibration of PTR-MS
      data with olfactometric assessment of odour concentration showing the possibility
      of a relatively good estimation of odour concentration by instrumental data. We
      will also show how the rapid PTR-MS fingerprint can be used to visualise the
      overall effect of a biofilter on the VOCs concentration and to calculate the
      reduction of the concentration of single masses and, finally, we will provide
      examples of the performances of a new implementation of this technique based on a
      time of flight (TOF) analyser. Instead of the usual quadrupole mass filter, the
      TOF provides an increase of analytical information and the possibility to
      separate important compounds that in the quadrupole version were not or only
      indirectly quantifiable. In conclusion we suggest that PTR-MS analysis can be a
      valuable tool for the rapid and on site monitoring of odour emission and plant
      operation.

PMID- 19380991
TI  - Extreme events: being prepared for the pitfalls with progressing sustainable
      urban water management.
AB  - It is widely accepted that new, more sustainable approaches to urban water
      management are required if cities and ecosystems are to become resilient to the
      effects of growing urban populations and global warming. Climate change
      predictions show that it is likely that cities around the world will be subject
      to an increasing number of extreme and less predictable events including flooding
      and drought. Historical transition studies have shown that major events such as
      extremes can expedite the adoption of new practices by destabilising existing
      management regimes and opening up new windows of opportunity for change. Yet,
      they can also act to reinforce and further entrench old practices. This case
      study of two Australian cities responding to extreme water scarcity reveals that
      being unprepared for extremes can undermine progress towards sustainable
      outcomes. The results showed that despite evidence of significant progress
      towards sustainable urban water management in Brisbane and Melbourne, the extreme
      water scarcity acted to reinforce traditional practices at the expense of
      emerging sustainability niches. Drawing upon empirical research and transitions
      literature, recommendations are provided for developing institutional mechanisms
      that are able to respond proactively to extreme events and be a catalyst for SUWM
      when such opportunities for change arise.

PMID- 19380992
TI  - Review of adverse health effects of odours in field studies.
AB  - Exposure to environmental odours from industrial and agricultural premises, in
      addition to inducing annoyance responses in a dose-dependent manner, have been
      shown to be either directly associated with gastric symptoms as well as general
      health-related complaints under extreme exposure conditions, or indirectly
      mediated through odour annoyance under moderate odour exposure conditions.
      OBJECTIVE: In order to examine the influence of hedonic tone (pleasantness
      unpleasantness) and perceived odour strength (intensity) on symptom reporting the
      results of two pertinent field studies were analysed. METHODS: In the vicinity of
      six industrial plants (sweets, rusk, textile, seed-oil, fat, cast iron) and
      eleven livestock operations (poultry, pig, cattle) assessment of odour exposure
      was done by means of systematic field inspections. Effect assessment was done by
      means of direct interviews (industrial: N=1456, agricultural: N=1053) using
      questionnaires covering odour annoyance, symptom reporting and relevant
      covariates. DATA ANALYSIS: Multiple logistic regression analysis was used to
      establish dose-response associations between odour frequency, intensity and
      hedonic tone as independent variables and symptom reporting as dependent
      variable. RESULTS: Exposure-symptom associations are strongly influenced by
      hedonic tone, whereas intensity has no additional predictive value. Adding odour
      annoyance to the regression model shows that symptom reporting is exclusively
      mediated by annoyance.

PMID- 19380993
TI  - On-line microwave total solids sensoring in sewage characterization.
AB  - We describe a novel application for a microwave on-line sensor to measure the
      total solids (TS) load entering a municipal wastewater treatment plant (WWTP)
      from slaughterhouse sewage and some sanitary wastewaters. Measuring this kind of
      wastewater stream is very challenging, because it contains a high, but varying
      organic load with nitrogen, phosphorus and microorganisms. The reliability of the
      measured signal was studied by comparison with laboratory analyses and a
      correlation is presented of TS-value with other parameters that are typically
      followed in a wastewater treatment process. The results suggest that on-line
      microwave sensoring could be used to monitor total solids in wastewater influent.
      Our results show that the on-line microwave sensor and laboratory reference
      analyses give similar results with a good correlation between the two techniques.
      Furthermore, we demonstrate that the total solids values correlate well with
      conductivity, total nitrogen and BOD(7) values but not with phosphorus, pH and
      temperature.

PMID- 19380994
TI  - Performance evaluation of UASB reactor systems with and without post-treatment.
AB  - This article evaluates and compares the actual behavior of 18 UASB reactor
      systems operating without (10 plants) and with (8 plants) post treatment,
      considering their performance and their reliability in terms of compliance with
      specified discharge standards. The following types of post-treatment processes
      were analyzed: aerated filter; anaerobic filter; trickling filter; dissolved air
      flotation unit; facultative pond and maturation pond. The effluent quality and
      the removal efficiencies were compared with typical values reported in the
      technical literature. A methodology developed by Niku et al. (1979) was used for
      the determination of the coefficients of reliability, in terms of the compliance
      of effluent BOD and TSS with discharge standards. The results showed that, in
      general, the inclusion of a post-treatment step, be it either aerobic, anaerobic
      or physical-chemical, can provide a substantial improvement of the effluent
      quality from UASB reactors in terms of BOD and TSS. In terms of the systems
      reliability, the actual effluent concentrations from UASB reactor followed by
      some post-treatment processes would meet more restrictive discharge standards
      than those considered in this study (60 mg L(-1) for both constituents-values
      prevailing in most states in Brazil).

PMID- 19380995
TI  - Shock loading in biofilters: impact on biodegradation activity distribution and
      resilience capacity.
AB  - A synthetic contaminated gas was generated, representative of gaseous emissions
      from sludge composting. It was composed of six volatile organic compounds
      (aldehyde, ketones, esters, sulphur compound) in an ammoniacal matrix. The
      gaseous stream was purified by biofiltration, in pilot scale biofilters filled
      with pine bark woodchips as organic carrier for biomass colonization. After
      reaching a constant high efficiency, with complete removal, the system was
      disturbed by transient loading shocks. The impact of perturbations was assessed
      by both performance evaluation (i.e. contaminant removal) and microbial
      behaviour. The microbial community was analysed in terms of density. The
      resilience of functional component following a perturbation was evaluated. This
      work highlighted the longitudinal distribution of both biodegradation activities
      and biomass density.

PMID- 19380996
TI  - Absorption and biodegradation of hydrophobic volatile organic compounds:
      determination of Henry's constants and biodegradation levels.
AB  - Biodegradation of three volatile organic compounds (VOCs) was studied. Toluene,
      dimethylsulphide (DMS), and dimethyldisulphide (DMDS) were introduced into flasks
      filled with emulsions of Di-2-EthylHexylAdipate (DEHA) in water, containing
      biomass (activated sludge). The VOC concentrations were analysed in the gas,
      organic and aqueous phases, and compared to the initial VOC quantities introduced
      in order to deduce their consumption by biomass. Toluene and DMDS were completely
      consumed, and then removed from the gas and the organic phases, except when DEHA
      and water are in the same volume ratio, which appears to be extreme environmental
      conditions for bacterial growth. The high DMS volatility resulted in an important
      gas loss, leading to a lower amount of DMS available for activated sludge growth.
      For all the VOC experiments, some components, characteristics of the DEHA
      degradation, including 2-ethylhexanal, 2-ethylhexanol, 2-ethylhexanoic acid and
      adipic acid, were identified.

PMID- 19380997
TI  - Development of a kinetic model for elemental sulfur and sulfate formation from
      the autotrophic sulfide oxidation using respirometric techniques.
AB  - A kinetic model for the elemental sulfur and sulfate production from the
      autotrophic sulfide oxidation has been proposed. It is based on two kinetic
      equations able to describe the simultaneous microbial consumption of oxygen and
      sulfide (OUR and SUR) as a function of a particular sulfide-oxidizing
      microorganism or its physiological state, these can be characterized by the
      assessment of their kinetic constants. The respirometric technique allowed to
      estimate the dynamic experimental OUR and SUR profiles, which were used to
      calibrate the kinetic model. The ratio OUR/SUR was proposed to predict the
      sulfide oxidation extent and then the fate of sulfide to elemental sulfur and
      sulfate.

PMID- 19380999
TI  - Difference in the odor concentrations measured by the triangle odor bag method
      and dynamic olfactometry.
AB  - 'The triangle odor bag method', which has been adopted for the offensive odor
      control law in Japan, and the dynamic olfactometry defined by EN 13725 have been
      compared. The odor concentration measured by the triangle odor bag method tends
      to be higher than that of the dynamic olfactometry in the forced choice mode,
      while well agreed in the Yes/No mode olfactometry when the panel is the same. The
      difference can be minimized by applying the panel selection criterion of EN13725
      to the triangle odor bag method. The European panel selection test is useful to
      negate the difference in the measurement equipments although the criteria seem to
      be strict considering the individual threshold data of n-butanol.

PMID- 19380998
TI  - Characterization of the bacterial community in a biotrickling filter treating
      high loads of H(2)S by molecular biology tools.
AB  - The diversity and spatial distribution of bacteria in a lab-scale biotrickling
      filter treating high loads of hydrogen sulfide (H(2)S) were investigated.
      Diversity and community structure were studied by terminal-restriction fragment
      length polymorphism (T-RFLP). A 16S rRNA gene clone library was established. Near
      Full-length 16S rRNA gene sequences were obtained, and clones were clustered into
      24 operational taxonomic units (OTUs). Nearly 74% and 26% of the clones were
      affiliated with the phyla Proteobacteria and Bacteroidetes, respectively. Beta-,
      epsilon- and gamma-proteobacteria accounted for 15, 9 and 48%, respectively.
      Around 45% of the sequences retrieved were affiliated to bacteria of the sulfur
      cycle including Thiothrix spp., Thiobacillus spp. and Sulfurimonas denitrificans.
      Sequences related to Thiothrix lacustris accounted for a 38%. Rarefaction curve
      demonstrated that clone library constructed can be sufficient to describe the
      vast majority of the bacterial diversity of this reactor operating under strict
      conditions (2,000 ppm(v) of H(2)S). A spatial distribution of bacteria was found
      along the length of the reactor by means of the T-RFLP technique. Although
      aerobic species were predominant along the reactor, facultative anaerobes had a
      major relative abundance in the inlet part of the reactor, where the sulfide to
      oxygen ratio is higher.

PMID- 19381000
TI  - Coagulation/flocculation of dye-containing solutions using polyaluminium chloride
      and alum.
AB  - This study aims to compare the performance of Polyaluminium Chloride (PAC) and
      alum as coagulants to remove a specific type of dye (Acid Blue 292 (AB292)) from
      dye-containing solution. For this purpose, the influence of pH, coagulant dosage,
      coagulant aids (kaolinite and bentonite), and initial dye concentration on dye
      removal efficiency were examined. According to the results, removal of AB292 was
      absolutely dependent on the pH variations. The maximum dye removal occurred when
      pH was 7 and 5 for PAC and alum, respectively. Both coagulants efficiently
      removed the dye (about 85%) with a relatively low dosage (40 mg/l) in their
      optimum pH range. By adding kaolinite as a coagulant aid, the removal
      efficiencies tended to increase, especially for lower dosages of PAC and alum.
      With the increase of initial dye concentration, PAC and alum represented
      different behaviors. In the case of PAC, Q (the amount of the removed dye per
      unit mass of coagulant) increased at first and reached to a maximum value, 2.1 mg
      dye/mg PAC, and then decreased rapidly. While for alum, Q steadily increased with
      the increase of dye concentration and reached to 2.8 mg dye/mg alum. No reduction
      of Q occurred for alum with the increase of dye concentration in the range of 25
      250 mg/l.

PMID- 19381001
TI  - Removal of hydrogen sulfide and ammonia from gas mixtures by co-immobilized cells
      using a new configuration of two biotrickling filters.
AB  - The simultaneous removal of H(2)S and NH(3) was investigated using two
      biotrickling filters packed with polyurethane foam cubes. One biotrickling filter
      was inoculated with Thiobacillus thioparus ATCC 23645 for the removal of H(2)S
      (BTT) and the other filter with Nitrosomonas europaea ATCC 19718 for the removal
      of NH(3) (BNE). Three different configurations were studied by modification of
      the gas line and recirculation medium line. The best results were obtained with
      the BNE biotrickling filter after the co-immobilization of the two bacteria. A
      removal efficiency of 100% for 230 ppmv of NH(3) and 129 ppmv of H(2)S was
      reached at an EBRT of 60 seconds. The results obtained show that it is possible
      to co-immobilize both microorganisms using the same recirculation medium and
      remove successfully H(2)S and NH(3) from a gas mixture.

PMID- 19381002
TI  - Multifactorial optimization of the decolorisation parameters of wastewaters
      resulting from dyeing flowers.
AB  - This work deals with the treatment of the wastewaters resulting from the process
      of dyeing flowers. In some local cases for growing flowers near to Medellin
      (Colombia), wastewater color was found to be one of the main problems in meeting
      local effluent standards. Wastewaters were treated by photodegradation process
      (which includes photocatalysis) to achieve the degradation of dyes mixture and
      organic matter in the wastewater. A multifactorial experimental design was
      proposed, including as experimental factors the following variables: pH, and the
      concentration of both catalyst (TiO(2)) and hydrogen peroxide (H(2)O(2)).
      According to the obtained results, at the optimized variables values, it is
      possible to reach a 99% reduction of dyes, a 76.9% of mineralization (TOC) and a
      final biodegradability of 0.834. Kinetic analysis allows proposing a pseudo first
      order reaction for the reduction, the mineralization, and the biodegradation
      processes.

PMID- 19381003
TI  - Removal of odour-causing compounds using carbonaceous adsorbents/catalysts
      prepared from sewage sludge.
AB  - This paper discusses H(2)S, NH(3) and VOCs removal by sewage-sludge-derived
      materials with outstanding chemical and textural properties. These materials were
      obtained from different precursors using different chemical and thermal
      treatments. Results show that the H(2)S removal process entailed a catalytic
      conversion of H(2)S to S or SO(4) (2-) species. On the other hand, adsorption is
      the main mechanism governing the performance of sludge-based materials for NH(3)
      and VOCs. Retention capacities (x/M values) obtained for some of the sludge-based
      adsorbents/catalysts are similar to those obtained with commercial activated
      carbons selected as reference materials.

PMID- 19381004
TI  - Odour, covering and ventilation.
AB  - A technique is described based on the decay in concentration of added SF(6) to
      measure L(0), the rate of leakage from an enclosure with no extraction of air. It
      is believed this measurement is much more precise than measurements of E(0), the
      minimum rate of extraction which just prevents leakage. Three out of four
      enclosures studied had L(0) values equating to residence times of air that were
      well under one hour. Relationships were developed between extraction rate and
      concentration and emission rate for enclosed odour sources based on mass transfer
      from water to air. These could be used to assess the benefits of minimising
      extraction rates while remaining within concentration limits set on the grounds
      of corrosion or toxicity. From these relationships a critical flow can be
      identified, termed Q(50), at which both the emission rate and concentration of a
      particular species are at 50% of their maximum value. In any particular system,
      Q50 for one species, such as H(2)S, will in general not be the same as for
      another species, nor for odour concentration. As a consequence the benefit of
      reducing extraction rates based on H(2)S may not appear as good as it would based
      on an assessment of odour concentration. A second consequence is that as the rate
      of air extraction is varied, the ratio between two species or between H(2)S and
      odour concentration, is likely to vary.

PMID- 19381005
TI  - The holistic prioritisation of proactive sewer maintenance.
AB  - In sewerage asset management, there has been a concerted move away from primarily
      assessing system capacity or physical performance, to focus on "serviceability"
      as a key performance indicator. After identifying flooding due to blockages as a
      key failure mode, this paper documents the development of a tool which can
      contribute towards efficient sewerage asset management within the context of
      maintaining "serviceability" to customers, the public and the environment.
      Against the background of poor availability of reliable data, the reported
      project provides a process based on FMECA which can be implemented with limited
      information and without the need for additional data gathering. Land use and
      network characteristics data have been used alongside a hydrodynamic model to
      determine critical points in a network. Based on this, a methodology for
      identifying where blockage likelihood lies is outlined alongside an approach
      which allows failure consequence to be quantified. The text then outlines a
      framework which allows failure likelihood and consequence to be combined to
      prioritise sewerage asset maintenance.

PMID- 19381006
TI  - The land use plan and water quality prediction for the Saemangeum reclamation
      project.
AB  - As the final closure of the world's longest sea dike of 33 km, the use of the
      Saemangeum reclaimed land becomes an issue in Korea. The Korean government has
      proclaimed that the Saemangeum Reclamation Project will be handled in an
      environmentally friendly manner but its effect on the water quality of reservoirs
      has always been controversial. This study was conducted to estimate the water
      quality of the Saemangeum reservoir using WASP5 according to the new land use
      plan adopted in 2007. Predictions on water quality shows that Dongjin reservoir
      would meet the standards for COD, T-P, and Chl-a if the wastewater from the
      Dongjin region was properly managed. However, T-P and Chl-a in Mangyeong
      reservoir would exceed the standards even without releasing the treated
      wastewater into the reservoir. With further reductions of 20% for T-P and Chl-a
      from the mouth of Mangyeong river, the water quality standards in the reservoir
      were achieved. This means that additional schemes, as well as water quality
      management programs established in the Government Master Plan in 2001, should be
      considered. Although the Saemangeum reservoir would manage to achieve the
      standards, it will enter a eutrophic state due to the high concentration of
      nutrients.

PMID- 19381007
TI  - Estimation of uncertainty in olfactometry.
AB  - Estimation of uncertainty in odour measurement is essential to the interpretation
      of the measurement results. The fundamental procedure for the estimation of
      measurement uncertainty comprises the specification of the measurement process,
      expression of the measurement model and all influences, evaluation of the
      standard uncertainty of each component, calculation of the combined standard
      uncertainty, determination of a coverage factor, calculation of the expanded
      uncertainty and reporting. Collaborative study such as interlaboratory comparison
      of olfactometry yields performance indicators of the measurement method including
      repeatability and reproducibility. Therefore, the use of collaborative test
      results for measurement uncertainty estimation according to ISO/TS 21748 and ISO
      20988 is effective and reasonable. Measurement uncertainty of the triangular
      odour bag method was estimated using interlaboratory comparison data from 2003 to
      2007 on the basis of the simplest model of statistical analysis, and the expanded
      uncertainty of odour index ranged between 3.1 and 6.7. On the basis of the
      establishment of the estimation procedure for uncertainty, a coherent
      interpretation method for the measurement results will be proposed and more
      effective and practical quality control of olfactometry will be available.

PMID- 19381008
TI  - Biological sulfide removal under alkaline and aerobic conditions in a packed
      recycling reactor.
AB  - The biological sulfide removal from wastewater caustic streams can be achieved
      without significant dilution by alkaliphilic microorganisms which usually show
      lower growth and oxidation rates as compared with acidic and neutral bacteria. To
      improve volumetric removal rates under alkaline condition (pH 10), an
      Alkaliphilic Sulfide-oxidizing Bacteria Consortium (ASBC) was studied in a Packed
      Recycling Reactor (PRR). A commercial Nylon fiber resulted to be a convenient
      packing support for biofilm development as it has high specific area and similar
      hydrophobic propertie. The PRR reached a maximum sulfide oxidation rate of 100
      mmol L(-1) d(-1) with efficiency close to 100%, representing an enhancement of
      56% from the maximum sulfide oxidation rate reached for a free cell continuous
      culture. Higher sulfide loading rates induced oxygen limiting conditions reducing
      the biological activity despite the considerable biofilm attached on the nylon
      fiber.

PMID- 19381009
TI  - Synthesis of Ag-ZnO nanoparticles for enhanced photocatalytic degradation of acid
      red 88 in aqueous environment.
AB  - Photocatalytic activities were found to be enhanced when noble metals were
      deposited on the semiconductors because the metal nanoparticles store electrons
      within them and in turn are recognized to act as a sink for photoinduced charge
      carriers, promoting interfacial charge transfer processes. This motivates us to
      modify the bare ZnO powder by doping with nano sized silver to yield metal
      semiconductor nanocomposites by simple material syntheses route to suppress
      detrimental recombination of the photogenerated charge carriers. The materials
      were characterized by different analytical techniques and it is potentially
      utilized for the photocatalytic degradation of an azo dye (Acid Red 88; AR88) in
      the visible region (lambda>400 nm). A possible mechanism for the photocatalytic
      degradation of AR88 by Ag-ZnO in the absence and presence of other oxidizing
      agents (peroxomonosulfate (PMS), peroxodisulfate (PDS) & hydrogen peroxide
      (H(2)O(2))) has been proposed. The extent of mineralization of the target
      pollutant was also evaluated using Total Organic Carbon (TOC) analysis.

PMID- 19381010
TI  - Development of compact UASB/trickling filter systems for treating domestic
      wastewater in small communities in Brazil.
AB  - The paper analyses the concept and performance of compact UASB/TF systems in
      relation to configuration, use of innovative packing media and operational
      conditions. For the conditions tested, the UASB/TF systems had consistently
      complied with the Brazilian discharge standard regarding to COD, BOD and TSS
      parameters. However, some enhancements are still necessary in order to increase
      nitrification in the process. The conditions to promote nitrification in shallow
      TF (packed bed up to 2.50 m height) seem to be compatible with the proposed
      simplification in the flowsheet, which is to operate the system without secondary
      clarifiers.

PMID- 19381011
TI  - Apparent hydrogen consumption in acid reactors: observations and implications.
AB  - Investigations of hydrogen production by dark fermentation have received
      increasing attention as a green fuel production process. Research focus is mainly
      on yields and rates of hydrogen production under different operation conditions.
      The importance of hydrogen consumption is addressed here, based on results from
      lab-scale reactors. Experiments were run using mixed cultures and a variety of
      operating conditions: HRT 6-40 hours; temperature 25-55 degrees C. Initial
      hydrogen yields between 0.8-1.5 mol H(2)/mol glucose and approximately 50% H(2)
      in headspace was observed, followed by a decrease in hydrogen production as the
      culture matures, resulting in hydrogen yields down to 0.02 mol H(2)/mol glucose.
      It is concluded that hydrogen or "hydrogen equivalents" consumption is
      significant, especially in reactors with high biomass concentration and/or high
      sludge age. Sustainable H(2) production by dark fermentation alone is therefore
      not likely to be developed. The results suggest that it is possible to control
      and avoid significant H(2) production in dark fermentation. Minimizing H(2)
      production can be useful in preparation of organic feed for other bio-fuel
      production processes, such as methanogenic processes and bio-electrochemical H(2)
      production.

PMID- 19381012
TI  - Anaerobic biodegradation of 2,4,6-trichlorophenol by methanogenic granular
      sludge: role of co-substrates and methanogenic inhibition.
AB  - The influence of several co-substrates in the anaerobic biodegradation of 2,4,6
      trichlorophenol (246TCP) by methanogenic granular sludge as well as in
      methanogenesis inhibition by 246TCP has been studied. 4 g-COD.L(-1) of lactate,
      sucrose, volatile fatty acids (VFA) acetate:propionate:butyrate 1:1:1, ethanol,
      methanol, yeast extract (YE), and 2 g-COD.L(-1) of formate and methylamine were
      tested. Two concentrations of 246TCP: 80 mg.L(-1) and 113 mg.L(-1) (this last
      corresponding to the EC(50) for acetotrophic methanogenesis) were tested. Three
      consecutive co-substrate and nutrient feedings were accomplished. 246TCP was
      added in the second feed, and the 246TCP removal rate increased considerably
      after the third feed. Accumulated metabolites after ortho-dechlorination, either
      4-chlorophenol (4CP) (when methanol, ethanol or VFA were used as co-substrates)
      or 2,4-dichlorophenol (24DCP) (with lactate) avoided the complete dechlorination
      of 246TCP. With methylamine and formate this compound was degraded only
      partially. Monochlorophenols biodegradation was partially achieved with YE, but
      both 24DCP and 2,6-dichlorophenol (26DCP) were accumulated. In the presence of
      sucrose para-dechlorination was observed. 246TCP was better tolerated by
      methanogens when ethanol and methanol were added because of the highest specific
      methanogenic activity achieved with these co-substrates. Methanol and ethanol
      were the best co-substrates in the anaerobic biodegradation of 246TCP.

PMID- 19381013
TI  - VEGF ameliorates pulmonary hypertension through inhibition of endothelial
      apoptosis in experimental lung fibrosis in rats.
AB  - Idiopathic pulmonary fibrosis (IPF) can lead to the development of secondary
      pulmonary hypertension (PH) and ultimately death. Despite this known association,
      the precise mechanism of disease remains unknown. Using a rat model of IPF, we
      explored the role of the proangiogenic and antiapoptotic growth factor VEGF in
      the vascular remodeling that underlies PH. In this model, adenoviral delivery of
      active TGF-beta1 induces pulmonary arterial remodeling, loss of the
      microvasculature in fibrotic areas, and increased pulmonary arterial pressure
      (PAP). Immunohistochemistry and mRNA analysis revealed decreased levels of VEGF
      and its receptor, which were inversely correlated with PAP and endothelial cell
      apoptosis in both the micro- and macrovasculature. Treatment of IPF rats with
      adenoviral delivery of VEGF resulted in reduced endothelial apoptosis, increased
      vascularization, and improved PAP due to reduced remodeling but worsened PF.
      These data show that experimental pulmonary fibrosis (PF) leads to loss of the
      microvasculature through increased apoptosis and to remodeling of the pulmonary
      arteries, with both processes resulting in PH. As administration of VEGF
      ameliorated the PH in this model but concomitantly aggravated the fibrogenic
      process, VEGF-based therapies should be used with caution.

PMID- 19381014
TI  - Self-regulation of inflammatory cell trafficking in mice by the leukocyte surface
      apyrase CD39.
AB  - Leukocyte and platelet accumulation at sites of cerebral ischemia exacerbate
      cerebral damage. The ectoenzyme CD39 on the plasmalemma of endothelial cells
      metabolizes ADP to suppress platelet accumulation in the ischemic brain. However,
      the role of leukocyte surface CD39 in regulating monocyte and neutrophil
      trafficking in this setting is not known. Here we have demonstrated in mice what
      we believe to be a novel mechanism by which CD39 on monocytes and neutrophils
      regulates their own sequestration into ischemic cerebral tissue, by catabolizing
      nucleotides released by injured cells, thereby inhibiting their chemotaxis,
      adhesion, and transmigration. Bone marrow reconstitution and provision of an
      apyrase, an enzyme that hydrolyzes nucleoside tri- and diphosphates, each
      normalized ischemic leukosequestration and cerebral infarction in CD39-deficient
      mice. Leukocytes purified from Cd39-/- mice had a markedly diminished capacity to
      phosphohydrolyze adenine nucleotides and regulate platelet reactivity, suggesting
      that leukocyte ectoapyrases modulate the ambient vascular nucleotide milieu.
      Dissipation of ATP by CD39 reduced P2X7 receptor stimulation and thereby
      suppressed baseline leukocyte alphaMbeta2-integrin expression. As alphaMbeta2
      integrin blockade reversed the postischemic, inflammatory phenotype of Cd39-/-
      mice, these data suggest that phosphohydrolytic activity on the leukocyte surface
      suppresses cell-cell interactions that would otherwise promote thrombosis or
      inflammation. These studies indicate that CD39 on both endothelial cells and
      leukocytes reduces inflammatory cell trafficking and platelet reactivity, with a
      consequent reduction in tissue injury following cerebral ischemic challenge.

PMID- 19381015
TI  - Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral
      adiposity and lipids and decreases insulin sensitivity in overweight/obese
      humans.
AB  - Studies in animals have documented that, compared with glucose, dietary fructose
      induces dyslipidemia and insulin resistance. To assess the relative effects of
      these dietary sugars during sustained consumption in humans, overweight and obese
      subjects consumed glucose- or fructose-sweetened beverages providing 25% of
      energy requirements for 10 weeks. Although both groups exhibited similar weight
      gain during the intervention, visceral adipose volume was significantly increased
      only in subjects consuming fructose. Fasting plasma triglyceride concentrations
      increased by approximately 10% during 10 weeks of glucose consumption but not
      after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and
      the 23-hour postprandial triglyceride AUC were increased specifically during
      fructose consumption. Similarly, markers of altered lipid metabolism and
      lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized
      LDL, and postprandial concentrations of remnant-like particle-triglyceride and 
      cholesterol significantly increased during fructose but not glucose consumption.
      In addition, fasting plasma glucose and insulin levels increased and insulin
      sensitivity decreased in subjects consuming fructose but not in those consuming
      glucose. These data suggest that dietary fructose specifically increases DNL,
      promotes dyslipidemia, decreases insulin sensitivity, and increases visceral
      adiposity in overweight/obese adults.

PMID- 19381016
TI  - Substance P stimulates human airway submucosal gland secretion mainly via a CFTR
      dependent process.
AB  - Chronic bacterial airway infections are the major cause of mortality in cystic
      fibrosis (CF). Normal airway defenses include reflex stimulation of submucosal
      gland mucus secretion by sensory neurons that release substance P (SubP). CFTR is
      an anion channel involved in fluid secretion and mutated in CF; the role of CFTR
      in secretions stimulated by SubP is unknown. We used optical methods to measure
      SubP-mediated secretion from human submucosal glands in lung transplant tissue.
      Glands from control but not CF subjects responded to mucosal chili oil.
      Similarly, serosal SubP stimulated secretion in more than 60% of control glands
      but only 4% of CF glands. Secretion triggered by SubP was synergistic with
      vasoactive intestinal peptide and/or forskolin but not with carbachol; synergy
      was absent in CF glands. Pig glands demonstrated a nearly 10-fold greater
      response to SubP. In 10 of 11 control glands isolated by fine dissection, SubP
      caused cell volume loss, lumen expansion, and mucus flow, but in 3 of 4 CF
      glands, it induced lumen narrowing. Thus, in CF, the reduced ability of mucosal
      irritants to stimulate airway gland secretion via SubP may be another factor that
      predisposes the airways to infections.

PMID- 19381017
TI  - Kidney dendritic cell activation is required for progression of renal disease in
      a mouse model of glomerular injury.
AB  - The progression of kidney disease to renal failure correlates with infiltration
      of mononuclear immune cells into the tubulointerstitium. These infiltrates
      contain macrophages, DCs, and T cells, but the role of each cell type in disease
      progression is unclear. To investigate the underlying immune mechanisms, we
      generated transgenic mice that selectively expressed the model antigens ovalbumin
      and hen egg lysozyme in glomerular podocytes (NOH mice). Coinjection of ovalbumin
      specific transgenic CD8+ CTLs and CD4+ Th cells into NOH mice resulted in
      periglomerular mononuclear infiltrates and inflammation of parietal epithelial
      cells, similar to lesions frequently observed in human chronic
      glomerulonephritis. Repetitive T cell injections aggravated infiltration and
      caused progression to structural and functional kidney damage after 4 weeks.
      Mechanistic analysis revealed that DCs in renal lymph nodes constitutively cross
      presented ovalbumin and activated CTLs. These CTLs released further ovalbumin for
      CTL activation in the lymph nodes and for simultaneous presentation to Th cells
      by distinct DC subsets residing in the kidney tubulointerstitium. Crosstalk
      between tubulointerstitial DCs and Th cells resulted in intrarenal cytokine and
      chemokine production and in recruitment of more CTLs, monocyte-derived DCs, and
      macrophages. The importance of DCs was established by the fact that DC depletion
      rapidly resolved established kidney immunopathology. These findings demonstrate
      that glomerular antigen-specific CTLs and Th cells can jointly induce renal
      immunopathology and identify kidney DCs as a mechanistic link between glomerular
      injury and the progression of kidney disease.

PMID- 19381018
TI  - Requirement for Ca2+/calmodulin-dependent kinase II in the transition from
      pressure overload-induced cardiac hypertrophy to heart failure in mice.
AB  - Ca2+/calmodulin-dependent kinase II (CaMKII) has been implicated in cardiac
      hypertrophy and heart failure. We generated mice in which the predominant cardiac
      isoform, CaMKIIdelta, was genetically deleted (KO mice), and found that these
      mice showed no gross baseline changes in ventricular structure or function. In WT
      and KO mice, transverse aortic constriction (TAC) induced comparable increases in
      relative heart weight, cell size, HDAC5 phosphorylation, and hypertrophic gene
      expression. Strikingly, while KO mice showed preserved hypertrophy after 6-week
      TAC, CaMKIIdelta deficiency significantly ameliorated phenotypic changes
      associated with the transition to heart failure, such as chamber dilation,
      ventricular dysfunction, lung edema, cardiac fibrosis, and apoptosis. The ratio
      of IP3R2 to ryanodine receptor 2 (RyR2) and the fraction of RyR2 phosphorylated
      at the CaMKII site increased significantly during development of heart failure in
      WT mice, but not KO mice, and this was associated with enhanced Ca2+ spark
      frequency only in WT mice. We suggest that CaMKIIdelta contributes to cardiac
      decompensation by enhancing RyR2-mediated sarcoplasmic reticulum Ca2+ leak and
      that attenuating CaMKIIdelta activation can limit the progression to heart
      failure.

PMID- 19381019
TI  - Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive
      multiple myeloma in mice.
AB  - Overexpression of FGF receptor 3 (FGFR3) is implicated in the development of
      t(4;14)-positive multiple myeloma. While FGFR3 is frequently overexpressed and/or
      activated through mutations in bladder cancer, the functional importance of FGFR3
      and its potential as a specific therapeutic target in this disease have not been
      elucidated in vivo. Here we report that inducible knockdown of FGFR3 in human
      bladder carcinoma cells arrested cell-cycle progression in culture and markedly
      attenuated tumor progression in xenografted mice. Further, we developed a unique
      antibody (R3Mab) that inhibited not only WT FGFR3, but also various mutants of
      the receptor, including disulfide-linked cysteine mutants. Biochemical analysis
      and 2.1-A resolution crystallography revealed that R3Mab bound to a specific
      FGFR3 epitope that simultaneously blocked ligand binding, prevented receptor
      dimerization, and induced substantial conformational changes in the receptor.
      R3Mab exerted potent antitumor activity against bladder carcinoma and t(4;14)
      positive multiple myeloma xenografts in mice by antagonizing FGFR3 signaling and
      eliciting antibody-dependent cell-mediated cytotoxicity (ADCC). These studies
      provide in vivo evidence demonstrating an oncogenic role of FGFR3 in bladder
      cancer and support antibody-based targeting of FGFR3 in hematologic and
      epithelial cancers driven by WT or mutant FGFR3.

PMID- 19381022
TI  - [Deep vein thrombosis in patients with cancer].
AB  - Malignancy can cause deep vein thrombosis(DVT)through: extrinsic compression;
      venous stasis due to intravenous invasion; secondary factors such as prolonged
      bed rest; and malignancy-induced abnormal coagulation and fibrinolysis. Various
      factors secreted from malignant tumors can reportedly cause systemic
      hypercoagulation, and tumor cells activate monocytes and macrophages to release
      tumor necrotic factor(TNF)-a and interleukin(IL)-6, which damage endothelial
      cells. Of the various onset factors for DVT, malignancy accounts for 15.6% in
      Japan, but discovery of malignancy at the onset of DVT or during follow-up is not
      rare, and malignancy is often involved with recurrent DVT or idiopathic DVT
      without a clear onset factor. Thorough testing must therefore be performed in
      patients with idiopathic or recurrent DVT while keeping malignancy in mind. As
      cancer patients are at risk for DVT, preventative management including
      hemorrhagic complication prevention is also required during surgery,
      chemotherapy, hormone therapy or prolonged bed rest.

PMID- 19381020
TI  - Susceptibility loci for murine HIV-associated nephropathy encode trans-regulators
      of podocyte gene expression.
AB  - Multiple studies have linked podocyte gene variants to diverse sporadic
      nephropathies, including HIV-1-associated nephropathy (HIVAN). We previously used
      linkage analysis to identify a major HIVAN susceptibility locus in mouse, HIVAN1.
      We performed expression quantitative trait locus (eQTL) analysis of podocyte
      genes in HIV-1 transgenic mice to gain further insight into genetic
      susceptibility to HIVAN. In 2 independent crosses, we found that transcript
      levels of the podocyte gene nephrosis 2 homolog (Nphs2), were heritable and
      controlled by an ancestral cis-eQTL that conferred a 3-fold variation in
      expression and produced reactive changes in other podocyte genes. In addition,
      Nphs2 expression was controlled by 2 trans-eQTLs that localized to the
      nephropathy susceptibility intervals HIVAN1 and HIVAN2. Transregulation of
      podocyte genes was observed in the absence of HIV-1 or glomerulosclerosis,
      indicating that nephropathy susceptibility alleles induce latent perturbations in
      the podocyte expression network. Presence of the HIV-1 transgene interfered with
      transregulation, demonstrating effects of gene-environment interactions on
      disease. These data demonstrate that transcript levels of Nphs2 and related
      podocyte-expressed genes are networked and suggest that the genetic lesions
      introduced by HIVAN susceptibility alleles perturb this regulatory pathway and
      transcriptional responses to HIV-1, increasing susceptibility to nephropathy.

PMID- 19381023
TI  - [Strategy for patients with GIST after failure of imatinib].
AB  - Sunitinib malate(SU11248)is an oral multitargeted receptor tyrosine kinase
      inhibitor(MTI)that has antitumor activities for patients with gastrointestinal
      stromal tumor; GIST after failure of Imatinib. Sunitinib has demonstrated
      significant clinical benefits, including PFS, RR and OS in the USA and Japan.
      However, cis-mutations in the activation loop of the KIT gene tend to develop
      Sunitinib-resistant GIST. Two clinical trials revealed that new multitargeted
      receptor tyrosine kinase inhibitors, Sorafenib and Nilotinib, had antitumor
      activities for Sunitinib-resistant GIST with longer PFS and a different spectrum.
      Now, clinical trials of several new MTIs are ongoing in Western countries.
      Inhibition of the KIT gene cis-mutations and antiangiogenesis activities may be
      essential for the strategy for Imatinib/Sunitinibresistant GIST.

PMID- 19381021
TI  - Anti-TNF immunotherapy reduces CD8+ T cell-mediated antimicrobial activity
      against Mycobacterium tuberculosis in humans.
AB  - The incidence of tuberculosis is increased during treatment of autoimmune
      diseases with anti-TNF antibodies. This is a significant clinical complication,
      but also provides a unique model to study immune mechanisms in human
      tuberculosis. Given the key role for cell-mediated immunity in host defense
      against Mycobacterium tuberculosis, we hypothesized that anti-TNF treatment
      impairs T cell-directed antimicrobial activity. Anti-TNF therapy reduced the
      expression in lymphocytes of perforin and granulysin, 2 components of the T cell
      mediated antimicrobial response to intracellular pathogens. Specifically, M.
      tuberculosis-reactive CD8+CCR7-CD45RA+ effector memory T cells (TEMRA cells)
      expressed the highest levels of granulysin, lysed M. tuberculosis, and infected
      macrophages and mediated an antimicrobial activity against intracellular M.
      tuberculosis. Furthermore, TEMRA cells expressed cell surface TNF and bound the
      anti-TNF therapeutic infliximab in vitro, making them susceptible to complement
      mediated lysis. Immune therapy with anti-TNF was associated with reduced numbers
      of CD8+ TEMRA cells and decreased antimicrobial activity against M. tuberculosis,
      which could be rescued by the addition of CD8+ TEMRA cells. These results suggest
      that anti-TNF therapy triggers a reduction of CD8+ TEMRA cells with antimicrobial
      activity against M. tuberculosis, providing insight into the mechanism whereby
      key effector T cell subsets contribute to host defense against tuberculosis.

PMID- 19381024
TI  - [Circumventing resistance to imatinib therapy in chronic myeloid leukemia].
AB  - In the emergence of resistance to imatinib, ABL-kinase inhibitor has become a
      significant problem despite the remarkable clinical results achieved with this
      drug in the treatment of chronic myeloid leukemia. The most common cause of
      imatinib resistance is the selection of leukemic clones with point mutation in
      the ABL-kinase domain. Persistent disease is another therapeutic challenge and
      may in part, be due to the inability of imatinib to eradicate primitive stem cell
      progenitors. A multitude of novel agents have been developed and shown efficacy
      in overcoming imatinib resistance.

PMID- 19381025
TI  - [Rituximab resistance in B-cell lymphoma and its elimination].
AB  - Rituximab is commonly incorporated into CD20-positive B-cell lymphoma therapy to
      improve response and prognosis. With increasing use, resistance to rituximab is a
      continuing concern, but CD20 mutation as a cause of resistance has not previously
      been reported. Freshly collected lymphoma cells from 50 patients with previously
      untreated or relapsed/resistant non-Hodgkin's B-cell lymphomas(diffuse large B
      cell, n=22; follicular, n=7; mucosa associated lymphoid tissue, n=16; chronic
      lymphocytic leukemia, n=2; small lymphocytic lymphoma, n=1; lymphoplasmacytic, n
      =1; mantle cell lymphoma, n=1)were assessed for CD20 expression by flow
      cytometry, and CD20 gene sequencing was performed on extracted DNA. CD20
      mutations were found in 11 of 50 patients(22.0%), and could be grouped as: C
      terminal deletion(8.0%), early termination(10.0%), and extracellular
      domain(2.0%)or transmembrane domain (2.0%)mutations. The mean fluorescence
      intensity of CD20 on fresh lymphoma cells was significantly lower for the
      Cterminal deletion mutation(3.26; 95% CI: 0.09-6.89)compared with wild type(30.8;
      95% CI: 22.4-39.2)(p<0.05). In contrast, early termination mutations did not show
      significant differences in CD20 expression compared with wild type (19.5; 95% CI:
      10.7-28.4)(p>0.05). It is possible that C-terminal deletion mutations of CD20 may
      be related to relapse/resistance after rituximab therapy. These mutations should
      be examined in patients showing progression of disease after partial remission.
      Other mechanisms are also discussed.

PMID- 19381026
TI  - [Overcoming resistance to EGFR-TKI in lung cancer].
AB  - Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor(TKI)as molecular
      targeted agents has given us an innovative strategy for treatment of patients
      with advanced non-small cell lung cancer(NSCLC). Patients with activating
      mutations of the EGFR generally respond to EGFR-TKI very well. HER3 has an
      essential role to enhance the EGFR signaling pathway, including the downstream
      pathway of PI3K/Akt pathway. The acquired resistance to EGFRTKI was clinically
      developed in patients with activating EGFR mutations. Recently, various
      mechanisms of acquired resistance have been developed, such as T790M, MET
      amplification, HGF increasing as a ligand of MET. We have to treat patients with
      NSCLC in the manor of individual medicine strategy today.

PMID- 19381027
TI  - [Molecular targeted therapy in colorectal cancer and its resistance].
AB  - The prognosis of advanced colorectal cancer has been improved by introduction of
      molecular targeting agents, such as bevacizumab and cetuximab. Several clinical
      trials revealed a median survival time of more than 2 years. However, the main
      purpose of chemotherapy for advanced colorectal cancer has not been cure but
      prolongation of life to date. One explanation of the difficulty of cure is the
      inherent and/or acquired resistance to chemotherapeutic agents and molecular
      targeting agents. A better understanding of the mechanisms of inherent resistance
      will make it possible to identify predictive markers of responder or non
      responder to select the optimal patients for a certain drug. Additionally,
      knowledge of the acquired mechanism will provide for the rational development of
      therapies that circumvent or overcome resistance. Although the mechanisms of the
      resistance of molecular targeting agents for colorectal cancer are still unclear,
      the inherent resistance to cetuximab or panitumumab by why of expression of KRAS
      mutation is the first breakthrough in this field. Further basic research and
      biomarker analysis of large clinical study are necessary to clarify the
      resistance to molecular targeting agents.

PMID- 19381028
TI  - [Drug resistance mediated by survival- and growth-promoting signaling pathways].
AB  - The serine/threonine kinases, Akt and Pim, are key molecules for cell signaling
      downstream of growth factors, cytokines and other stimuli. Akt and Pim kinases
      regulate cellular processes that are associated with the aggressiveness of a
      number of different cancers. They protect cells from undergoing apoptosis and
      promote cell growth by phosphorylating their downstream substrates, which lead to
      the occurrence of resistance to anti-cancer drugs and radiation. Activation of
      Akt and Pim by transfecting their expression plasmids or by modulating their
      regulators attenuated the cytotoxic effects of anti-tumor drugs. Thus, the
      pathways are attractive targets for enhancing the sensitivity to and overcoming
      resistance to anti-cancer drugs. Recently, several small molecular inhibitors
      targeting the components of the Akt and Pim signaling pathways have been
      developed, and some inhibitors have already entered clinical trials. Further,
      some interesting associated proteins and substrates of the pathways have been
      identified. In future, new therapy targeting Akt and Pim signaling pathways will
      be developed to selectively induce apoptosis in cancer cells and to overcome drug
      resistance.

PMID- 19381029
TI  - [Risk associated with severe hematological toxicity in patients with advanced or
      recurrent gastric cancer receiving primary combination chemotherapy of cisplatin
      and S-1 or cisplatin and irinotecan hydrochloride].
AB  - The purpose of this study was to analyze the risk factor for grade 3 to 4
      hematological toxicity after primary chemotherapy(cisplatin(CDDP)/tegafur,
      gimeracil, oteracil potassium(S1)or CDDP/irinotecan hydrochloride(CPT-11)) in 75
      patients with unresectable or recurrent gastric cancer between April 2005 and May
      2008. The rate of grade 3 to 4 hematological toxicity was 17.3%(13 patients).
      Grade 3 to 4 hematological toxicity was the endpoint selected for the analysis.
      At multivariate analysis, the most important pretreatment risk factors for grade
      3 to 4 hematological toxicity in patients receiving primary chemotherapy of
      unresectable or recurrent gastric cancer were found to be hemoglobin(OR 0.520;
      p=0.012)and treatment regimen(CDDP/CPT-11)(OR 0.101; p=0.002). Therefore,
      patients about to receive chemotherapy should be considered in these risk
      factors.

PMID- 19381030
TI  - [Administration of S-1 after gastrojejunostomy for unresectable gastric cancer
      with pyloric stenosis].
AB  - We evaluated the efficacy of chemotherapy using S-1 after gastrojejunostomy for
      unresectable gastric cancer with pyloric stenosis. We performed gastrojejunostomy
      to relieve obstruction in 40 patients from 1993 to 2007. After gastrojejunostomy,
      15 patients were treated with S-1(S-1 group), 12 patients were treated with
      another anticancer drug(non S-1 group)and the other 13 patients received no
      chemotherapy. After informed consent was obtained, S-1(80 mg/m(2)day)and another
      anticancer drug was administered. The mean period of administered was 16(range 2
      56)weeks in the S-1 group. In the non S-1 group, 5-FU was used in 1 patient, 5'
      DFUR in 2, UFT in 3, FP chemotherapy in 3, CPT- 11/CDDP chemotherapy in 1, and 5
      FU/PTX chemotherapy was conducted in 2 patients. The one-year survival rate was
      63% and the median survival time was 394 days in the S-1 group, against 33% and
      169 days, respectively, in the non S-1 group. Appetite loss of grade 3 was
      observed in one(7%)patient with nonhematological toxicity, but no patient
      suffered grade 3 hematological toxicity. We observed the course of all patients
      on an outpatient basis. In conclusion, S- 1 administration after
      gastrojejunostomy appears to be an effective treatment modality for far advanced
      gastric cancer patients with pyloric stenosis in view of toxicities, antitumor
      effects and QOL of the patients.

PMID- 19381031
TI  - [Treatment of leptomeningeal carcinomatosis from gastric cancer].
AB  - Leptomeningeal carcinomatosis is a serious complication leading to a fatal
      outcome in patients with gastric cancer. We tried to treat leptomeningeal
      carcinomatosis from gastric cancer with intrathecal chemotherapy using
      methotrexate (MTX)and cytosine arabinoside(Ara-C). We described and discussed the
      therapeutic strategy. Six patients with leptomeningeal carcinomatosis from
      gastric cancer were admitted in our institution from March 2004 to July 2007.
      Three of 6 patients were accepted for intrathecal chemotherapy. They received
      intraventricular injections of MTX(5 mg)and Ara-C(20 mg)through the Ommaya
      reservoir. The other 3 patients who rejected the therapy were conservatively
      treated with betamethasone, carbamazepine and glyceol. Two of the intrathecal
      chemotherapy group received whole-brain radiotherapy after the initial
      intrathecal chemotherapy. The mean survival time was 122.3 days(median survival
      time 35.0 days). The survival of the intrathecal chemotherapy group was from 39
      to 367 days, whereas the survival of the conservative treatment group was from 10
      to 31 days. The intrathecal chemotherapy improved not only survival but also
      clinical symptoms dramatically. Intrathecal chemotherapy is thus recommended for
      leptomeningeal carcinomatosis from gastric cancer.

PMID- 19381032
TI  - [Concurrent chemoradiation experience of the local relapse of rectal cancer
      patients].
AB  - We have reported the concurrent chemoradiation experience of local relapse of
      rectal cancer patients. From October 2004 to January 2007 we have treated
      consecutive 10 patients with radiation and the concurrent chemotherapy by CPT
      11+S-1. Of 10 lesions, 5(50%)had a complete response, 2(20%)a partial response,
      3(30%)a stable disease, yielding an overall response rate of 70%. Three year
      survival and relapse free survival was 64% and 22 months, respectively. Four
      patients live without cancers, 3 patients died with cancers and 2 patients live
      with cancers. Three patients had acute complication(more than Grade 2)including 3
      appetite losses. The concurrent chemoradiation is feasible for out-patients and
      seems to offer good results for the local relapse of rectal cancer patients.

PMID- 19381033
TI  - [Histoculture drug response assay guided adjuvant chemotherapy in patients with
      ERCC1-positive non-small cell lung cancer].
AB  - PURPOSE: A previous large randomized control study(IALT)revealed that
      cisplatin(CDDP)-based adjuvant chemotherapy was not effective for patients with
      ERCC1-positive non-small cell lung cancer(NSCLC). We evaluated the
      chemosensitivity of surgically resected specimens of NSCLC using in vitro
      chemosensitivity test and searched for promising adjuvant chemotherapy protocols
      in the ERCC1-positive subgroup of NSCLC. PATIENTS AND METHODS: Chemosensitivities
      of 10 anticancer agents including cisplatin were evaluated by histoculture drug
      response assay(HDRA) using 28 surgically resected NSCLC specimens. ERCC 1 status
      was evaluated by immunohistochemistry. RESULTS: ERCC1 was positive in 22 and
      negative in 6 specimens. All ERCC1-negative specimens were sensitive for CDDP in
      HDRA, and all CDDP-resistant specimens in HDRA showed positive ERCC1 staining.
      ERCC1 status was significantly correlated with CDDP sensitivity(p=0.01). HDRA
      showed average 3(0-6)sensitive anticancer agents except for CDDP even in ERCC1
      positive specimens. CONCLUSION: HDRA may provide effective non-platinum adjuvant
      chemotherapy protocols for patients with ERCC1-positive, i.e. CDDP resistant,
      NSCLC.

PMID- 19381034
TI  - [Examination about the influence for daily life that nail and skin disorders
      induced by docetaxel in patients with breast cancer].
AB  - Docetaxel is one of the most important chemotherapeutic agents for the breast
      cancer patients. However, it has also experienced as toxicities causing nail
      diformation and skin trouble, and is considered as adverse elements other than
      edema and neurotoxicity. It is expected to have tremendous influence on women's
      daily life-decrease in quality of life. Nail and skin toxicity might occur among
      patients treated with docetaxel more frequently than evidence in the clinical
      medical records. Therefore, we have conducted a questionnaire investigation,
      targeting the patients who had been treated with docetaxel. Between March, 2004
      and February, 2006, 52 patients, who had been prescribed docetaxel at the time of
      the surgery, or for their relapse, became subject to the evaluation. Skin
      impediments have found most during the second and the third courses; the contents
      include discomfort towards their beauty and housework. Influence to their daily
      life that the patients feel do not necessarily match the contents that doctors
      have recognized. In conclusion, this investigation evidenced that the troubles on
      quality of life such as nail and skin troubles, should be paid more attention, as
      well as major side effects such as edema, neutropenia, and neurotoxicity.

PMID- 19381035
TI  - [Correlations between hormonal receptor and HER2 status or nuclear grades and
      response rate in breast cancer treated with neoadjuvant chemotherapy of docetaxel
      alone].
AB  - BACKGROUND: Neoadjuvant chemotherapy has been considered the standard care in
      locally advanced breast cancer. However, about 10-35% of the patients don't
      benefit from this treatment. This study was designed to evaluate predictive
      values of biological markers in response of breast cancers treated with docetaxel
      alone as neoadjuvant chemotherapy. METHODS: 36 patients received the planned four
      courses of preoperative docetaxel(60-75 mg/m(2)) every 3 weeks. We evaluated the
      relationship between the response rate to neoadjuvant chemotherapy and hormonal
      receptor, HER2 status or nuclear grades. RESULTS: Clinical response rate was
      57.2%. Pathological complete response rate was 5.6%. Clinical response rate by
      each factors were as follows; 9(50%)in ER-positive tumors, 10(66.7%)in
      ERnegative( p=0.27), 7(50%)in PgR-positive, 12(63.3%)in PgR-negative(p=0.34),
      5(55.6%)in HER2-positive, 14 (58.3%)in HER2-negative(p=0.71), 4(50%)in tumors of
      low nuclear grade and 13(65%)in ones of high nuclear grade(p=0.38). CONCLUSION:
      The possibility that tumors with negative hormonal receptors or of high nuclear
      grade tend to respond to neoadjuvant chemotherapy with docetaxel alone more
      likely was suggested. It is thought breast cancers respond to neoadjuvant
      chemotherapy of docetaxel alone regardless of HER2 status.

PMID- 19381036
TI  - [Efficacy of mirtazapine for appetite loss and nausea of the cancer patient--from
      clinical experience in Memorial Sloan-Kettering Cancer Center].
AB  - Mirtazapine is a noradrenergic and specific serotonergic antidepressant(NaSSA).
      Some studies reported that mirtazapine has a receptor-binding profile that may be
      suitable for use in controlling appetite loss and nausea of cancer patients. We
      examined its efficacy for these symptoms in 9 cases administered mirtazapine for
      9 days. After administration for 4-6 days, the efficacy of nausea was shown at 15
      mg of the initial dosage; it was particularly useful in a mild stage. However,
      its efficacy for appetite loss was not clear for these cases. This study was
      performed by an open trial. Because of the small number of cases and follow-up
      period, future study is awaited.

PMID- 19381037
TI  - [Two cases of recurrent oral cancer responding to radiochemotherapy with
      selective intra-arterial infusion of nedaplatin].
AB  - Nedaplatin, a cisplatin derivative, has been reported to be an effective anti
      tumor agent for head and neck cancer. We experienced two patients with advanced
      recurrent oral cancers who received combination therapy of intra-arterial
      nedaplatin infusion and radiation therapy, and tumoricidal effects were obtained
      in these cases. At the end of 3 courses, a partial response(PR)was obtained with
      regression of the tumor in the first case, and FDGPET showed a complete
      regression of recurrent tumor for a complete response(CR)in another case. This
      combination therapy is quite safe and effective for the treatment of advanced
      oral cancers.

PMID- 19381038
TI  - [A long-term recurrence-free survivor after chemotherapy with 5-FU plus CDDP and
      surgery for small cell carcinoma of the esophagus].
AB  - We report a case of small cell carcinoma of the esophagus(SCEC)treated by
      chemotherapy with 5-fluorouracil(5- FU)plus cisplatin(CDDP)and operation. A 60
      year-old man was seen at the hospital because of a sensation of food sticking in
      his throat at meals. Gastrointestinal endoscopy revealed a type 2 tumor in the
      middle portion of the esophagus, which was pathologically diagnosed as small cell
      carcinoma. With a diagnosis of SCEC, preoperative chemotherapy with 5-FU plus
      CDDP was given. Primary lesion showed complete response. After chemotherapy, an
      operation was performed. The tumor had histopathologically disappeared, and the
      patient has been free of any signs of recurrence, as of 6 years 2 months after
      the operation. Primary small cell carcinoma of the esophagus is a rare disease
      with early systemic metastasis, and the prognosis remains poor. In a review of
      the literature, all patients with SCEC who had survived for 2 years or more had
      undergone combined therapies including operation, chemotherapy and radiotherapy.
      This study deals with a long-term surviving patient without any signs of
      recurrence after excision of the foci followed by chemotherapy.

PMID- 19381039
TI  - [Gastrojejunostomy for irresectable gastric cancer with pyloric stenosis-new role
      of surgery in the era of S-1].
AB  - We report a patient with an advanced gastric cancer complicated by pyloric
      stenosis who was effectively treated by S-1 mono-therapy after gastrojejunostomy.
      A 62-year-old man consulted a general practitioner for abdominal pain and
      anorexia. Gastric roentgenography and upper gastrointestinal endoscopy showed
      gastric cancer(Borrmann Type 3) with pyloric stenosis. He was referred to our
      department. He underwent laparotomy, which revealed a T4 tumor invading the
      pancreas head, but neither liver nor peritoneal metastasis. A gastrojejunostomy
      was made. After the operation, chemotherapy of S-1(120 mg/day, day 1
      21)+cisplatin(100 mg/day, day 8)was administered. After 2 courses, level of tumor
      marker decreased remarkably and abdominal enhanced computed tomography showed a
      significant size reduction of lymph nodes and that direct invasion to the
      pancreas was not clear any more. Second laparotomy was carried out and curative
      surgery was performed. After 4 courses of S-1(120 mg/day, day 1 approximately
      28)mono-therapy as adjuvant chemotherapy, bone metastasis was confirmed by
      scintigram. Then methotrexate+5-FU, irinotecan+cisplatin and cisplatin+paclitaxel
      were chosen as second-, third-and fourth-line chemotherapy, which were not
      effective for long. He died 572 a days after the initial surgery. In the past,
      gastrojejunostomy was regarded as useful palliative treatment for those with
      gastric outlet stenosis to ameliorate the QOL. As S-1 is taking major role in the
      chemotherapy for advanced gastric cancer recently, usefulness of bypass surgery
      for such patients is highlighted even for longer survival time.

PMID- 19381040
TI  - [A case of advanced gastric cancer effectively treated with paclitaxel/S-1 as
      neoadjuvant chemotherapy].
AB  - We report a patient with advanced gastric cancer responding remarkably to
      neoadjuvant combination chemotherapy consisting of paclitaxel and S-1. The
      patient was a 65-year-old female who had large type 2 advanced gastric cancer
      with severe lymph node metastasis(cT3, cN3, cH0, cP0, cM0, cStage IV), treated
      with paclitaxel/S-1 as neoadjuvant chemotherapy. After the second course,
      according to UGI, gastroscope and CT findings, a significant tumor reduction was
      obtained. Distal gastrectomy with D2 nodal dissection were performed. The
      histological diagnosis was pT1, pN1, pStage IB. The histological effect of main
      tumor was judged to be Grade 2. The patient has now been in good health without a
      recurrence for 10 months after surgery. This case suggests that neoadjuvant
      chemotherapy with paclitaxel/ S-1 is a potential regimen for advanced gastric
      cancer.

PMID- 19381041
TI  - [A case of drug induced interstitial pneumonitis after gemcitabine treatment for
      pancreatic carcinoma].
AB  - A 67-year-old male with pancreatic cancer(cStage IVb)was given gemcitabine on
      days 1, 8 and 15, and this was repeated on 29 days at dose of 800 mg/m(2) in
      outpatient clinic. After 2 courses, he suffered from dyspnea and fever.
      Laboratory examination showed that the serum levels of white cell count, C
      reactive protein, lactate dehydrogenase and KL-6 were elevated. Chest X-ray and
      CT revealed diffuse bilateral interstitial infiltrates. He was diagnosed with
      drug induced interstitial pneumonia due to gemcitabine. Corticosteroid therapy
      consisting of methylprednisolone(1,000 mg/day)for three days followed by
      prednisolone was effective and he was discharged on the 29th day after admission.
      Gemcitabine is an anti-cancer agent of first-line chemotherapy for patient with
      pancreatic carcinoma. Acute pulmonary toxicity induced by gemcitabine could lead
      to severe complication. We should consider the possibility of drug induced
      interstitial pneumonitis duringg emcitabine therapy.

PMID- 19381043
TI  - [A case of locally advanced rectal cancer responding to FOLFOX].
AB  - The 57-year-old man was underwent sigmoid colostomy due to unresectable rectal
      carcinoma. Then he was treated with chemotherapy of levofolinate/5
      fluorouracil/oxaliplatin(FOLFOX). After completion of 12 courses of chemotherapy,
      MR revealed responses. The patient underwent a low anterior resection.
      Preoperative chemotherapy with FOLFOX appears a promising regimen for patients
      with unresectable rectal cancer.

PMID- 19381042
TI  - [A case report of FOLFOX treatment for primary duodenal carcinoma with multiple
      liver metastases].
AB  - We report a case of a woman in her sixties having primary duodenal carcinoma with
      multiple liver metastases who was treated with oxaliplatin in combination with
      infusional 5-fluorouracil/Leucovorin(FOLFOX regimen). After completing 2 courses
      of the chemotherapy, computed tomography showed a partial response without any
      severe adverse events. Now at 8 months, the PR stage has been maintained. So far,
      no standard therapeutic strategy for metastatic duodenal carcinoma has been
      developed. However, we suggest a FOLFOX regimen can be highly effective as a safe
      approach for continuously maintaining the quality of life of patients with this
      rare type of cancer.

PMID- 19381044
TI  - [A successfully resected case of rectal cancer with liver metastases treated with
      mFOLFOX6 and bevacizumab].
AB  - A sixties-man had complained of melena. Colonoscopy revealed type 2 tumor at
      rectum. Computed tomography (CT)demonstrated lymph node metastasis in front of
      sacrum and two low density areas which were suspected metastases in the liver.
      The patient was diagnosed stageIV rectal cancer and resected primary focus and
      lymph node metastasis.[ Ra-RS, ant, type 2, moderately differentiated
      adenocarcinoma, ly1, v3, pSE, pN2, sH1(Grade C), sP0, pM1(No. 270)]without liver
      resection. It was due to high level of CEA and remote lymph node metastasis. The
      patient was treated with mFOLFOX6 and bevacizumab after the operation. The level
      of CEA decreased to normal level and CT revealed a partial response after 4
      cycles of systemic chemotherapy. Liver resection was performed safely.
      Histological response was Grade 2 at liver metastases.

PMID- 19381045
TI  - [A case report of complete response to RPMI regimen for multiple lymph node
      metastases following rectal cancer surgery].
AB  - A 78-year old man underwent low anterior resection for Stage IIIb rectal
      cancer(Ra). After surgery, he underwent the Roswell Park Memorial
      Institute(RPMI)regimen for 6 months followed by oral UFT for 8 months. Since
      liver metastasis(S6)recurred 2 years and 2 months after surgery, he underwent S6
      subsegmentectomy. Four years and 4 months later, he developed multiple lymph node
      metastases(the Virchow, paraaortic, and intrapelvic lymph nodes), for which
      FOLFIRI therapy was started, but converted to the RPMI regimen because of strong
      gastrointestinal side effects. After 3 courses of this regimen, tumor markers
      returned to normal, and imaging studies showed that the metastases had
      disappeared. This was interpreted as a complete response(CR). The patient has
      maintained the complete response for 1 year and 4 months since the start of the
      RPMI regimen.

PMID- 19381046
TI  - [A case of metastatic breast cancer resistant to anastrozole treatment responding
      to high-dose toremifene].
AB  - The patient was a 56-year-old female. At the age of 35 years, she had under gone
      left mastectomy and axillary lymph node dissection for breast cancer. After
      surgery, hormonal therapy was continued for 3 years. Then, no treatment was
      performed. In this study, single therapy with an AI agent was started to
      treatbilateral supraclavicular fossa/mediastinal lymphnode metastases. After 6
      months, a partial response(PR)was achieved. However, progression of the
      disease(PD)was noted after 1 year. Thereafter,the regimen was switched to single
      high-dose(120mg/day)TOR therapy. CT revealed the disappearance of the bilateral
      supraclavicular fossa lymphnodes and a marked reduction of the other lymphnodes.
      Currently, the patient is being treated, with an interval of 10 months from the
      start of TOR therapy.

PMID- 19381047
TI  - [A case of non-small cell lung cancer with EGFR mutation responding to S-1 after
      a therapy with gefitinib].
AB  - A 78-year-old man had underwent right upper lobectomy for lung adenocarcinoma in
      July 1998(pT1N0M0, pStage Ia). In January2003, computed tomography showed a tumor
      in right lower lobe of lung, which grew slowly. He was treated with UFT. In April
      2004, computed tomographyshowed multiple nodules in both lung, which was
      considered of metastasis of lung cancer. The increase of the nodules were
      observed, and treatment with gefitinib was started. Insertion mutation at EGFR in
      exon 20 was seen from the primarylung cancer. Since tumor growth occurred despite
      gefitinib administration, we converted gefitinib into S-1 using 80 mg/day for 28
      days, followed by 14 days rest. Chest computed tomographyshowed a partial
      response. No side effect was observed, and continued internal use of S-1 until
      January 2007 when it was impossible to continue, and meanwhile, the increase of
      the tumor was not seen.

PMID- 19381048
TI  - [A patient with multiple skin metastases from breast cancer responding to S-1
      effectively under treatment with trastuzumab].
AB  - We report a case of a 52-year-old female with multiple skin metastases from
      breast cancer who responded to S-1. She underwent surgery of her right breast in
      March 2000 and the left in June 2006. Multiple skin metastases were later
      detected. As there was no hormone sensitivity, chemotherapy was selected. We
      started treatment with administration of S-1 at 120mg/day(4 weeks)and
      trastuzumab. Thoracic CT at the end of the three courses revealed the
      disappearance of the multiple skin metastases. No major side effects were seen.
      It was concluded from these findings that S-1 could be safely and effectively
      administered to advanced breast cancer patients.

PMID- 19381049
TI  - [Significance of urinary uracil measurement following administration of DPD
      inhibitory fluoropyrimidine(DIF)products].
AB  - Individual differences in 5-FU metabolism are mainly attributed to individual
      differences in the activity of DPD, an enzyme that can metabolize more than 85%
      of 5-FU. Because urinary uracil is a reflection of DPD activity, it is measured
      to predict and prevent the occurrence of side effects caused by pyrimidine-type
      chemotherapeutic agents. From urinary uracil values measured in 84
      gastrointestinal cancer patients, 0-60 mmol/g.creatinine was set as a standard.
      In patients whose urinary uracil values exceeded the standard, 5-FU tended to be
      accumulated when S-1, a DIF product, was administered and side effects, such as
      anorexia, vomiting and diarrhea occurred immediately after the start of S-1
      administration. If an appropriate DIF product is selected and its dosage set
      based on the patient's urinary uracil value, the occurrence of side effects would
      be reduced. Subsequently, a continuation of medication would be possible.

PMID- 19381050
TI  - [Role of pharmaceutical company pharmacist in provision of drug information for
      cancer chemotherapy].
AB  - Recently, oxaliplatin(L-OHP)and irinotecan hydrochloride hydrate(CPT-11)have
      gained recognition as key drugs in the treatment of advanced colorectal cancer.
      In this article, we describe the results of a survey of medical institutions by
      pharmacists working at a pharmaceutical company. First, questions from medical
      institutions on L-OHP and CPT-11 were totaled and analyzed. The results showed
      that most of these questions concerned safety, with many of these addressing side
      effects. Next, a questionnaire on FOLFOX and FOLFIRI regimens was administered to
      medical institutions. The results indicated that staff are interested in the
      safety and critical path of these regimens. These results suggest that a lot of
      medical institutions require more information from pharmaceutical companies. This
      indicates that pharmacists should do more to take the needs of medical
      institutions into account in providing improved customer support.

PMID- 19381051
TI  - [Involvement of medical representatives in team medical care].
AB  - In recent years, chemotherapies have been further advanced because of successive
      launch of new drugs, introduction of molecular targeting, etc., and the concept
      of so-called Team Medical Care ,the idea of sharing interdisciplinary expertise
      for collaborative treatment, has steadily penetrated in the Japanese medical
      society. Dr. Naoto Ueno is a medical oncologist at US MD Anderson Cancer Center,
      the birthplace of the Team Medical Care. He has advocated the concept of ABC of
      Team Oncology by positioning pharmaceutical companies as Team C. Under such team
      practice, we believe that medical representatives of a pharmaceutical company
      should also play a role as a member of the Team Medical Care by providing
      appropriate drug use information to healthcare professionals, supporting post
      marketing surveillance of treated patients, facilitating drug information sharing
      among healthcare professionals at medical institutions, etc.

PMID- 19381052
TI  - [A case of gastric metaplasia of the duodenum].

PMID- 19381053
TI  - [Enhanced chemotherapeutic drug delivery to tumor tissue by high intensity
      focused ultrasound].
AB  - Cancer is the first leading cause of death in Korea. Systemic chemotherapy is
      currently the standard treatment for a wide variety of cancers; however, in the
      majority of cases, cure is not achieved, and the attendant side effects of the
      treatment are considerable. The effectiveness of chemotherapy in cancers depends
      on the adequate delivery of the chemotherapeutic agent to cancer cells. The
      achievement of uniform drug delivery of chemotherapeutic agents throughout tumors
      is limited by the anomalous vascularization and blood vessel permeability.
      Ultrasound has an ever-increasing role in the delivery of therapeutic agents
      including chemotherapeutic agents, proteins, and genetic materials. Ultrasound
      technology allows for the use of focused ultrasound energy for therapeutic
      purposes by delivering high-intensity focused ultrasound for applications such as
      tissue ablation, and enhanced drug delivery. We reviewed recent work in the
      emerging field of ultrasound-based therapeutics, with particular emphasis on the
      delivery of drugs to tumor tissue.

PMID- 19381054
TI  - [Inter-departmental differences in the eradication therapy for Helicobacter
      pylori infection: a single center study].
AB  - BACKGROUND/AIMS: Eradication rates of Helicobacter pylori (H. pylori) tend to
      decrease over the last few years. Apart from the antibiotic resistance and
      patients compliance, various factors have an influence on the efficacy of
      eradication therapy. We analyzed the inter-departmental differences in the
      eradication therapy for H. pylori infection. METHODS: Between January 2003 and
      June 2007, total 3,072 eradication regimens were prescribed to patients.
      Eradication rates according to departments - gastroenterology (GE), general
      internal medicine (IM) and family medicine (FM) - were analyzed retrospectively.
      RESULTS: The overall eradication rate of first-line triple therapy was 82.5% and
      second-line quadruple therapy was 71.2%. In the department of IM and FM, the
      eradication therapy was applied more frequently to the patients with erosion
      only, not ulcer. Overall eradication rates according to the departments were
      87.0% in GE, 81.1% in IM and 77.2% in FM (p=0.02 GE vs. IM and p<0.01 GE vs. FM,
      respectively). Eradication rate in patients with peptic ulcer was also
      significantly higher in GE compared with IM or FM. CONCLUSIONS: In primary clinic
      (IM and FM), the eradication therapy was frequently applied to erosion. The
      eradication rates of H. pylori in GE department were significantly higher than
      those of IM or FM. Inter-departmental differences of the eradication rate might
      be caused by patients' compliance to prescribed medication.

PMID- 19381055
TI  - [Effect of after-hours emergency endoscopy on the outcome of acute upper
      gastrointestinal bleeding].
AB  - BACKGROUND/AIMS: Gastrointestinal endoscopy is imperative for acute upper
      gastrointestinal bleeding (AUGIB) to find bleeding focus and stop bleeding. This
      study was designed to assess the necessity of emergency endoscopy and determine
      screening criteria for the patients who presented to emergency room (ER) with
      after-hours AUGIB. METHODS: The medical records of 383 patents with AUGIB who
      presented to ER at after-hours were reviewed. Patients were divided into 2
      groups: emergency endoscopy (EE) group (<12 hours after arrival) or delayed
      endoscopy (DE) group (12-24 hours after arrival). We compared the severity,
      hemostatic procedures, rebleeding rate, length of hospitalization and 30-day
      mortality between the two groups. RESULTS: Ninety-eight patients in EE group and
      137 patients in DE group were evaluated among patients with non-variceal upper
      gastrointestinal bleeding. No significant differences in clinical severity,
      finding the bleeding focus, hemostasis, 30-day mortality, hospital stay, and
      rebleeding rate were observed between the two groups. Among 148 patients with
      variceal upper gastrointestinal bleeding, 65 patients were in EE group and 83
      patients in DE group. Most clinical severity index were not different between the
      groups. In EE group, the rate of finding bleeding foci was lower (p=0.043), and
      30-day mortality was higher than in DE group (p=0.023). CONCLUSIONS: Emergency
      endoscopy within 12 hours after arrival at after-hours do not lead to better
      prognosis in AUGIB.

PMID- 19381056
TI  - [Is end stage renal disease a poor prognosis factor of ischemic colitis?].
AB  - BACKGROUND/AIMS: In general, ischemic colitis has a very good prognosis. However,
      there are a lot of controversies in relation to the prognostic factors. The aim
      of this study was to evaluate risk factors of severe ischemic colitis. METHODS: A
      retrospective study was undertaken of patients with ischemic colitis hospitalized
      at the Hanyang University Hospital during the interval 2004-2006. Patients were
      divided into two groups: those with mild course and those with severe course
      which led to operation, systemic inflammatory response syndrome, or death.
      RESULTS: A total of 41 cases (M/F=13/28, mean age=63.8 years) of biopsy proven
      ischemic colitis were included, of which 31 (75.6%) had a mild course and 10
      (24.4%) a severe course. Coexisting medical diseases of patients were
      hypertension (n=24), diabetes (n=14), end-stage renal disease (n=11),
      cardiovascular disease (n=5), and malignancy (n=5). Male (p=0.049), alcoholics
      (p=0.025), end-stage renal disease (p=0.013), LDH (p=0.002), CRP (p=0.014), and
      peritoneal irritation sign (p=0.001) were the significant risk factors of severe
      ischemic colitis in univariate analysis. In multivariate logistic regression
      analysis, end-stage renal disease (p=0.026) was the only significant risk factor
      of severe ischemic colitis. CONCLUSIONS: Careful attention must be paid to end
      stage renal disease patients having ischemic colitis.

PMID- 19381057
TI  - [Clinical characteristics of chronic pancreatitis according to the history of
      pancreatitis].
AB  - BACKGROUND/AIMS: Chronic pancreatitis (CP) is characterized clinically by a broad
      spectrum of variable features depending on many factors such as etiology, stage
      of the disease, and the presence of local complications. The aims of this study
      were to investigate the clinical aspect of CP and to analyze the characteristics
      according to the history of pancreatitis. METHODS: Eighty nine medical records
      from the patients who were diagnosed as CP at Korea University Ansan Hospital
      from January 1997 through December 2007 were reviewed retrospectively. After
      patients were divided into two groups according to the previous history of
      pancreatitis: the group I (n=34, no history of pancreatitis) and II (n=43,
      history of pancreatitis more than once), the clinical characteristics of two
      groups were compared. RESULTS: The mean age was 50+/-13.2 years and the male to
      female ratio was 5:1. Alcohol was the cause of CP in 71.9%, and 23.6% had no
      evident cause. Age (53.4+/-15.5 vs. 46.2+/-11.5, p=0.021), etiology (idiopathic
      41.2% vs. 11.6%, p=0.004), and the presence of abdominal pain (73.5% vs. 100%,
      p=0.030) were significantly different between group I and II. However, in
      comparison of other factors that reflected the advanced stage of CP such as
      presence of pancreatic calcification, complications, and Cambridge grade on ERCP,
      there was no significant difference. CONCLUSIONS: Since CP which present, as the
      first manifestation shows much an advanced stage, the method for early diagnosis
      of CP is particularly needed.

PMID- 19381058
TI  - [A case of small duodenal carcinoid tumor with liver metastasis].
AB  - Carcinoid tumors are slow growing submucosal tumors with metastatic potential
      that arise from enterochromaffin cell. The annual incidence of carcinoid tumor is
      2 to 3 per 100,000. Carcinoid tumor of duodenum is very rare with an incidence of
      about 8% among gastrointestinal carcinoid tumor. As a endoscopic examination and
      immunohistochemical stain are developed, an rate of detection is increasing.
      Among the possible factor of metastatic prediction, tumor size >10 mm, central
      depression or ulcer, invasion below submucosa, lymphatic or venous invasion are
      associated with higher metastatic potential. Specially, in case of tumor size <10
      mm, in duodenum, there is no report of metastasis to liver in Korea. But,
      recently, we experienced a rare care of duodenal carcinoid measured by less than
      10 mm with liver metastasis. Thus, we report here this case with a review of
      literature.

PMID- 19381059
TI  - [A case of idiopathic pancreatitis in a patient with Crohn's disease].
AB  - Pancreatitis has been occasionally associated with Crohn's disease (CD). A
      definite etiology of pancreatitis can be identified in most patients, but a very
      small proportion remain idiopathic. We report a case of idiopathic pancreatitis
      resolved along with the clinical improvement of CD in a 25-year-old man. He
      presented with abdominal pain and diarrhea for 8 years. Ileocolonoscopy and
      enteroclysis showed multiple, longitudinal ulcers and strictures at the
      ileojejunum. The laboratory findings showed elevated serum amylase (951 IU/L) and
      lipase (326 IU/L) without positive autoantibodies. Esophagogastroduodenoscopy,
      enhanced pancreatic CT, and MRCP showed no abnormalities at ampulla of Vater,
      pancrease, and pancreaticobiliary duct. With the treatment with antibiotics, 5
      aminosalicylic acid, steroid, and azathioprine, as a whole, decreasing pattern
      and intermittent fine coordinated fluctuation of the levels of amylase and lipase
      along with the decrease of Crohn's disease activity index (CDAI) and the CRP
      levels were observed. Then, three months after the start of the treatment,
      normalization of the pancreatic enzymes was observed, and there was recurrent
      elevation of pancreatic engyme during 12 months maintenance therapy. This report
      supports the concept of an association between idiopathic pancreatitis and CD,
      based on a significant and close relation between the levels of serum amylase and
      lipase, and CDAI.

PMID- 19381060
TI  - [A patient diagnosed as autoimmune pancreatitis 6 years after onset of jaundice].
AB  - The clinical manifestations of autoimmune pancreatitis (AIP) are diffuse
      pancreatic swelling, diffuse irregular narrowing of the main pancreatic duct, and
      increased serum IgG or positive serum autoantibody. Clinically, AIP can be
      improved dramatically with oral steroid therapy. In this report, we describe a 62
      year-old woman diagnosed as autoimmune pancreatitis six years after onset of
      jaundice, who presented with uncontrolled blood glucose levels. The laboratory
      tests revealed obstructive jaundice, and the computed tomography of the pancreas
      showed pancreatic swelling. After six years of onset, she was diagnosed with AIP
      and successfully treated with steroid treatment.

PMID- 19381061
TI  - [A case of actinomycosis of gallbladder presenting as acute cholecystitis].
AB  - Actinomycosis is a chronic suppurative and granulomatous disease, characterized
      by the formation of abscess, draining sinuses, abundant granulation, and dense
      fibrous tissue. Actinomycosis of the gallbladder is extremely rare. We report a
      case of an 56-years old man who abruptly presented with right upper quadrant
      abdominal pain. Abdominal CT showed that the gallbladder had 2 cm sized stone and
      an edematous thick wall. Our preoperative diagnosis was acute calculous
      cholecystitis. After the management of acute cholecystitis, laparoscopic
      cholecystectomy was performed but converted to open surgery due to severe
      adhesion to liver and greater omentum. Partial cholecystectomy was performed.
      Histologic section of the gallbladder showed sulfur granule with gram-positive
      branching bacilli compatible with actinomyces. After cholecystectomy, the patient
      received intravenous penicillin G for 2 weeks, followed by oral penicillin for 3
      months.

PMID- 19381062
TI  - [Prognostic value of emergency endoscopy in patient with upper gastrointestinal
      bleeding].

PMID- 19381064
TI  - Neuronal activation increases the density of eukaryotic translation initiation
      factor 4E mRNA clusters in dendrites of cultured hippocampal neurons.
AB  - Activity-dependent dendritic translation in CNS neurons is important for the
      synapse-specific provision of proteins that may be necessary for strengthening of
      synaptic connections. A major rate-limiting factor during protein synthesis is
      the availability of eukaryotic translation initiation factor 4E (eIF4E), an mRNA
      5-cap-binding protein. In this study we show by fluorescence in situ
      hybridization (FISH) that the mRNA for eIF4E is present in the dendrites of
      cultured rat hippocampal neurons. Under basal culture conditions, 58.7 +/-11.6%
      of the eIF4E mRNA clusters localize with or immediately adjacent to PSD-95
      clusters. Neuronal activation with KCl (60 mM, 10 min) very significantly
      increases the number of eIF4E mRNA clusters in dendrites by 50.1 and 74.5% at 2
      and 6 h after treatment, respectively. In addition, the proportion of eIF4E mRNA
      clusters that localize with PSD-95 increases to 74.4+/-7.7% and 77.8+/-7.6% of
      the eIF4E clusters at 2 and 6 h after KCl treatment, respectively. Our results
      demonstrate the presence of eIF4E mRNA in dendrites and an activity-dependent
      increase of these clusters at synaptic sites. This provides a potential mechanism
      by which protein translation at synapses may be enhanced in response to synaptic
      stimulation.

PMID- 19381065
TI  - Stimulatory heterotrimeric G protein augments gamma ray-induced apoptosis by up
      regulation of Bak expression via CREB and AP-1 in H1299 human lung cancer cells.
AB  - Stimulatory heterotrimeric GTP-binding proteins (Gs protein) stimulate cAMP
      generation in response to various signals, and modulate various cellular
      phenomena such as proliferation and apoptosis. This study aimed to investigate
      the effect of Gs proteins on gamma ray-induced apoptosis of lung cancer cells and
      its molecular mechanism, as an attempt to develop a new strategy to improve the
      therapeutic efficacy of gamma radiation. Expression of constitutively active
      mutant of the alpha subunit of Gs (GalphasQL) augmented gamma ray-induced
      apoptosis via mitochondrial dependent pathway when assessed by clonogenic assay,
      FACS analysis of PI stained cells, and western blot analysis of the cytoplasmic
      translocation of cytochrome C and the cleavage of caspase-3 and ploy(ADP-ribose)
      polymerase (PARP) in H1299 human lung cancer cells. GalphasQL up-regulated the
      Bak expression at the levels of protein and mRNA. Treatment with inhibitors of
      PKA (H89), SP600125 (JNK inhibitor), and a CRE-decoy blocked GalphasQL-stimulated
      Bak reporter luciferase activity. Expression of GalphasQL increased basal and
      gamma ray-induced luciferase activity of cAMP response element binding protein
      (CREB) and AP-1, and the binding of CREB and AP-1 to Bak promoter. Furthermore,
      prostaglandin E2, a Galphas activating signal, was found to augment gamma ray
      induced apoptosis, which was abolished by treatment with a prostanoid receptor
      antagonist. These results indicate that Galphas augments gamma ray-induced
      apoptosis by up-regulation of Bak expression via CREB and AP-1 in H1299 lung
      cancer cells, suggesting that the efficacy of radiotherapy of lung cancer may be
      improved by modulating Gs signaling pathway.

PMID- 19381066
TI  - Lysophosphatidylglycerol inhibits formyl peptide receptorlike-1-stimulated
      chemotactic migration and IL-1beta production from human phagocytes.
AB  - In this study, we observed that lysophosphatidylglycerol (LPG) completely
      inhibited a formyl peptide receptor like-1 (FPRL1) agonist (MMK-1)-stimulated
      chemotactic migration in human phagocytes, such as neutrophils and monocytes. LPG
      also dramatically inhibited IL-1beta production by another FPRL1 agonist serum
      amyloid A (SAA) in human phagocytes. However, LPG itself induced intracellular
      calcium increase and superoxide anion production in human phagocytes. Keeping in
      mind that phagocytes migration and IL-1beta production by FPRL1 are important for
      the induction of inflammatory response, our data suggest that LPG can be regarded
      as a useful material for the modulation of inflammatory response induced by FPRL1
      activation.

PMID- 19381067
TI  - Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic
      gluconeogenesis.
AB  - During fasting periods, hepatic glucose production is enhanced by glucagon to
      provide fuels for other organs. This process is mediated via cAMP-dependent
      induction of the CREB regulated transcriptional coactivator (CRTC) 2, a critical
      transcriptional activator for hepatic gluconeogenesis. We have previously shown
      that CRTC2 activity is regulated by AMP activated protein kinase (AMPK) family
      members. Here we show that adiponectin and thiazolidinedione directly regulate
      AMPK to modulate CRTC2 activity in hepatocytes. Adiponectin or thiazolidinedione
      lowered glucose production from primary hepatocytes. Treatment of both reagents
      reduced gluconeogenic gene expression as well as cAMP-mediated induction of CRE
      reporter, suggesting that these reagents directly affect CREB/CRTC2- dependent
      transcription. Furthermore, adiponectin or thiazolidinedione mediated repression
      of CRE activity is largely blunted by co-expression of phosphorylation defective
      mutant CRTC2, underscoring the importance of serine 171 residue of this factor.
      Taken together, we propose that adiponectin and thiazolidinedione promote the
      modulation of AMPK-dependent CRTC2 activity to influence hepatic gluconeogenesis.

PMID- 19381068
TI  - Angiotensin II-induced aortic ring constriction is mediated by
      phosphatidylinositol 3-kinase/L-type calcium channel signaling pathway.
AB  - Angiotensin II (AngII) is a crucial hormone that affects vasoconstriction and
      exerts hypertrophic effects on vascular smooth muscle cells. Here, we showed that
      phosphatidylinositol 3-kinase-dependent calcium mobilization plays pivotal roles
      in AngII-induced vascular constriction. Stimulation of rat aortic vascular smooth
      muscle cell (RASMC)-embedded collagen gel with AngII rapidly induced contraction.
      AngII-induced collagen gel contraction was blocked by pretreatment with a
      phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) whereas ERK inhibitor
      (PD98059) was not effective. AngII-induced collagen gel contraction was
      significantly blocked by extracellular calcium depletion by EGTA or by nifedipine
      which is an L-type calcium channel blocker. In addition, AngII-induced calcium
      mobilization was also blocked by nifedipine and EGTA, whereas intracellular
      calcium store-depletion by thapsigargin was not effective. Finally, pretreatment
      of rat aortic ring with LY294002 and nifedipine significantly reduced AngII
      induced constriction. Given these results, we suggest that PI3K-dependent
      activation of L-type calcium channels might be involved in AngII-induced vascular
      constriction.

PMID- 19381069
TI  - Ubiquitylation of Fe65 adaptor protein by neuronal precursor cell expressed
      developmentally down regulated 4-2 (Nedd4-2) via the WW domain interaction with
      Fe65.
AB  - Fe65 has been characterized as an adaptor protein, originally identified as an
      expressed sequence tag (EST) corresponding to an mRNA expressed at high levels in
      the rat brain. It contains one WW domain and two phosphotyrosine
      interaction/phosphotyrosine binding domains (PID1/PID2). As the neuronal
      precursor cell expressed developmentally down regulated 4-2 (Nedd4-2) has a
      putative WW domain binding motif ((72)PPLP(75)) in the N-terminal domain, we
      hypothesized that Fe65 associates with Nedd4-2 through a WW domain interaction,
      which has the characteristics of E3 ubiquitin-protein ligase. In this paper, we
      present evidence for the interaction between Fe65 WW domain and Nedd4-2 through
      its specific motif, using a pull down approach and co-immunoprecipitation.
      Additionally, the co-localization of Fe65 and Nedd4-2 were observed via confocal
      microscopy. Co-localization of Fe65 and Nedd4-2 was disrupted by either the
      mutation of Fe65 WW domain or its putative binding motif of Nedd4-2. When the
      ubiquitin assay was performed, the interaction of Nedd4-2 (wt) with Fe65 is
      required for the cell apoptosis and the ubiquitylation of Fe65. We also observed
      that the ubiquitylation of Fe65 (wt) was augmented depending on Nedd4-2
      expression levels, whereas the Fe65 WW domain mutant (W243KP245K) or the Nedd4-2
      AL mutant ((72)PPLP(75) was changed to (72)APLA(75)) was under-ubiquitinated
      significantly. Thus, our observations implicated that the protein-protein
      interaction between the WW domain of Fe65 and the putative binding motif of Nedd4
      2 down-regulates Fe65 protein stability and subcellular localization through its
      ubiquitylation, to contribute cell apoptosis.

PMID- 19381071
TI  - Protective effect of total aralosides of Aralia elata (Miq) Seem (TASAES) against
      diabetic cardiomyopathy in rats during the early stage, and possible mechanisms.
AB  - Total aralosides of Aralia elata (Miq) Seem (TASAES) from Chinese traditional
      herb Longya Aralia chinensis L was found to improve cardiac function. The present
      study was to determine the protective effects of TASAES on diabetic
      cardiomyopathy, and the possible mechanisms. Therefore, a single dose of
      streptozotocin was used to induce diabetes in Wister rats. Diabetic rats were
      immediately treated with low, medium and high doses of TASAES at 4.9, 9.8 mg/kg
      and 19.6 mg/kg body weight by gavage, respectively, for eight weeks. Cardiac
      function was evaluated by in situ hemodynamic measurements, and patch clamp for
      the L-type Ca2+ channel current I(Ca(2+)-L) and transient outward K+ channel
      current (I(to)). Histopathological changes were observed under light and electron
      microscope. The expression of pro-fibrotic factor, connective tissue growth
      factor (CTGF) was monitored using immunohistochemistry staining. Compared with
      diabetic group, medium and high doses, but not low dose, of TASAES showed a
      significant protection against diabetes-induced cardiac dysfunction, shown by
      increased absolute value of left ventricular systolic pressure (LVSP) and maximum
      rates of pressure development (+/-dp/dt(max)), and enhanced amplitude of I(Ca(2+)
      L) (P<0.05). Histological staining indicated a significant inhibition of diabetes
      caused pathological changes and up-regulation of CTGF expression (P< 0.05). The
      results suggest that TASAES prevents diabetes-induced cardiac dysfunction and
      pathological damage through up-regulating I(Ca(2+)-L) in cardiac cells and
      decreasing CTGF expression.

PMID- 19381070
TI  - Cordycepin inhibits UVB-induced matrix metalloproteinase expression by
      suppressing the NF-kappaB pathway in human dermal fibroblasts.
AB  - Cordycepin (3-deoxyadenosine) has been shown to exhibit many pharmacological
      activities, including anti-cancer, anti-inflammatory, and anti-infection
      activities. However, the anti-skin photoaging effects of cordycepin have not yet
      been reported. In the present study, we investigated the inhibitory effects of
      cordycepin on matrix metalloproteinase-1 (MMP-1) and -3 expressions of the human
      dermal fibroblast cells. Western blot analysis and real-time PCR revealed
      cordycepin inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent
      manner. UVB strongly activated NF-kappaB activity, which was determined by
      IkappaBalpha degradation, nuclear localization of p50 and p65 subunit, and NF
      kappaB binding activity. However, UVB-induced NF-kappaB activation and MMP
      expression were completely blocked by cordycepin pretreatment. These findings
      suggest that cordycepin could prevent UVB-induced MMPs expressions through
      inhibition of NF-kappaB activation. In conclusion, cordycepin might be used as a
      potential agent for the prevention and treatment of skin photoaging.

PMID- 19381074
TI  - Trends in three decades of HIV/AIDS epidemic in Thailand by nonparametric
      backcalculation method.
AB  - OBJECTIVES: To reconstruct the past HIV incidence and prevalence in Thailand from
      1980 to 2008 and predict the country's AIDS incidence from 2009 to 2011. METHODS:
      Nonparametric backcalculation was adopted utilizing 100 quarterly observed new
      AIDS counts excluding pediatric cases. The accuracy of data was enhanced through
      a series of data adjustments using the weight method to account for several
      surveillance reporting issues. The mixture of time-dependent distributions
      allowed the effects of age at seroconversion and antiretroviral therapy to be
      incorporated simultaneously. Sensitivity analyses were conducted to assess model
      variations that were subject to major uncertainties. Future AIDS incidence was
      projected for various predetermined HIV incidence patterns. RESULTS: HIV
      incidence in Thailand reached its peak in 1992 with approximately 115,000 cases.
      A steep decline thereafter discontinued in 1997 and was followed by another
      strike of 42,000 cases in 1999. The second surge, which happened concurrently
      with the major economic crisis, brought on 60,000 new infections. As of December
      2008, more than 1 million individuals had been infected and around 430,000 adults
      were living with HIV corresponding to a prevalence rate of 1.2%. The incidence
      rate had become less than 0.1% since 2002. The backcalculated estimates were
      dominated by postulated median AIDS progression time and adjustments to
      surveillance data. CONCLUSION: Our analysis indicated that, thus far, the 1990s
      was the most severe era of HIV/AIDS epidemic in Thailand with two HIV incidence
      peaks. A drop in new infections led to a decrease in recent AIDS incidence, and
      this tendency is likely to remain unchanged until 2011, if not further.

PMID- 19381076
TI  - Sexual transmission of HIV according to viral load and antiretroviral therapy:
      systematic review and meta-analysis.
AB  - OBJECTIVES: To synthesize the evidence on the risk of HIV transmission through
      unprotected sexual intercourse according to viral load and treatment with
      combination antiretroviral therapy (ART). DESIGN: Systematic review and meta
      analysis. METHODS: We searched Medline, Embase and conference abstracts from 1996
      2009. We included longitudinal studies of serodiscordant couples reporting on HIV
      transmission according to plasma viral load or use of ART and used random-effects
      Poisson regression models to obtain summary transmission rates [with 95%
      confidence intervals, (CI)]. If there were no transmission events we estimated an
      upper 97.5% confidence limit. RESULTS: We identified 11 cohorts reporting on 5021
      heterosexual couples and 461 HIV-transmission events. The rate of transmission
      overall from ART-treated patients was 0.46 (95% CI 0.19-1.09) per 100 person
      years, based on five events. The transmission rate from a seropositive partner
      with viral load below 400 copies/ml on ART, based on two studies, was zero with
      an upper 97.5% confidence limit of 1.27 per 100 person-years, and 0.16 (95% CI
      0.02-1.13) per 100 person-years if not on ART, based on five studies and one
      event. There were insufficient data to calculate rates according to the presence
      or absence of sexually transmitted infections, condom use, or vaginal or anal
      intercourse. CONCLUSION: Studies of heterosexual discordant couples observed no
      transmission in patients treated with ART and with viral load below 400
      copies/ml, but data were compatible with one transmission per 79 person-years.
      Further studies are needed to better define the risk of HIV transmission from
      patients on ART.

PMID- 19381075
TI  - Antiretroviral medication adherence and the development of class-specific
      antiretroviral resistance.
AB  - OBJECTIVE: To assess the association between antiretroviral adherence and the
      development of class-specific antiretroviral medication resistance. DESIGN AND
      METHODS: Literature and conference abstract review of studies assessing the
      association between adherence to antiretroviral therapy and the development of
      antiretroviral medication resistance. RESULTS: Factors that determine class
      specific adherence-resistance relationships include antiretroviral regimen
      potency, viral fitness or, more specifically, the interplay between the fold
      change in resistance and fold-change in fitness caused by drug resistance
      mutations, and the genetic barrier to antiretroviral resistance. During multidrug
      therapy, differential drug exposure increases the likelihood of developing
      resistance. In addition, antiretroviral medications with higher potency and
      higher genetic barriers to resistance decrease the incidence of resistance for
      companion antiretroviral medications at all adherence levels. CONCLUSION:
      Knowledge of class-specific adherence-resistance relationships may help
      clinicians and patients tailor therapy to match individual patterns of adherence
      in order to minimize the development of resistance at failure. In addition, this
      information may guide the selection of optimal drug combinations and regimen
      sequences to improve the durability of antiretroviral therapy.

PMID- 19381077
TI  - Sustained release of microbicides by newly engineered vaginal rings.
AB  - OBJECTIVE: An effective vaginal microbicide against sexual HIV transmission
      remains elusive, with requirements for adherence to appropriate application of
      effective, nontoxic products being a major deterrent. We explored methods to
      enable sustained release of combinations of antiretroviral microbicides,
      utilizing intravaginal rings composed of biosoluble Acacia gum or
      nonbiodegradable hydrogel of 2-hydroxyethyl methacrylate and sodium methacrylate,
      materials approved for use by the US Food and Drug Administration. DESIGN AND
      METHODS: The reverse transcriptase inhibitors TMC120, PMPA, 3'-azido-3'
      deoxythymidine, and a newly characterized anti-HIV agent, Boc-lysinated betulonic
      acid, were incorporated into vaginal rings with different combinations. Daily and
      cumulative release rates of these inhibitors in ring eluates were determined by
      high-performance liquid chromatography, gas chromatography, or immunoassay. Anti
      HIV effects were measured by assessment of p24 Gag antigen in T-cell cultures
      exposed to HIV-1 isolates. RESULTS: Drug release rates were sustained at
      concentrations higher than the minimum effective dose for HIV inhibition. The
      release was maintained for no less than 15 and 28 days from the Acacia gum and 2
      hydroxyethyl methacrylate and sodium methacrylate rings, respectively. Boc
      lysinated betulonic acid showed more than 90% inhibition of HIV-1 infection in H9
      cells, with little toxicity to normal cells. CONCLUSION: The intravaginal rings
      described here are capable of efficacious drug delivery. Incorporation of several
      antiretroviral agents, including betulinol derivatives, which act at multiple
      levels of the HIV life cycle, may provide a synergistic effect to achieve higher
      efficacy on the inhibition of HIV infection.

PMID- 19381079
TI  - Perineural invasion after preoperative chemotherapy predicts poor survival in
      patients with locally advanced gastric cancer: gene expression analysis with
      pathologic validation.
AB  - BACKGROUND: We examined gene expression profiles and clinicopathologic features
      (tumor location, stage, graded pathologic response, perineural invasion (PNI),
      Lauren's classification, and survival) of patients with gastric cancer who
      received preoperative chemotherapy to identify prognostic markers. METHODS:
      Thirty-eight patients with locally advanced gastric cancer received preoperative
      chemotherapy on a phase II trial. Twelve fresh-frozen tumor samples were
      available for RNA expression analysis. Differential gene expression between
      tumors with and without PNI was identified and correlated with clinicopathologic
      features. RESULTS: Preliminary hierarchical clustering suggested a separation
      between long- and short-term survivors. The close association between PNI and
      overall survival was identified and validated immunohistochemically in 31
      completely resected gastric tumors. Five-year survival for patients with PNI and
      without PNI was 5% and 65%, respectively (P < 0.01). PNI added significant
      prognostic value to posttreatment pathologic stage, (P < 0.01). Differential gene
      expression profile for PNI and non-PNI tumors identified 111 potentially relevant
      genes. CONCLUSIONS: Our results demonstrate that the presence of PNI after
      preoperative chemotherapy is associated with poor survival. These results need to
      be validated in prospective studies, to help establish whether patients with
      evidence of PNI would be candidates for more aggressive therapy or enrollment
      into clinical trials. The presence of PNI provides additional prognostic
      importance to posttreatment pathologic stage and may indicate treatment
      resistance. Understanding the molecular events associated with PNI, may provide
      insight into new therapeutic agents for this subset of patients with resistant
      tumors.

PMID- 19381080
TI  - Bladder conservation treatment in the elderly population: results and prognostic
      factors of muscle-invasive bladder cancer.
AB  - OBJECTIVES: To report the long-term results of bladder conservation strategies in
      elderly patients with muscle-invasive bladder cancer and evaluate the different
      factors affecting locoregional control and patient survival. METHODS: We reviewed
      the records of 39 elderly patients aged 70 or older, treated with curative intent
      with radiotherapy, with or without chemotherapy after transurethral resection of
      bladder for T2-T4aN0 carcinoma of the bladder. Twenty-seven men and 12 women were
      identified with a median age of 78 (range 70-87). Sixteen of the patients had a
      previous history of superficial bladder cancer. Twenty-five patients had T2
      lesions, 13 patients had T3 lesions, and 1 patient had T4a lesion. The majority
      of patients were unsuitable for surgery because of medical reasons (67%), whereas
      the others refused radical cystectomy (33%). Patients were treated with radical
      radiation therapy with or without chemotherapy. RESULTS: At a median follow-up
      time of 35.5 months for patients at risk, the 5-year overall survival is 28.9%
      for all stages, 31.9% for T2 lesions, and 26.8% for T3-T4a lesions. Significant
      prognostic factors for overall survival on univariate analysis were performance
      status and age. Five-year cause-specific survival is 37.5% for all stages, 41.5%
      for T2 lesions, and 34.7% for T3-T4a lesions. No significant prognostic factors
      for cause-specific survival were indentified on univariate analysis. Toxicity was
      acceptable. CONCLUSION: Younger age and good performance status were favorable
      prognostic factors for overall survival. Bladder conservation strategies achieved
      satisfactory results and were well-tolerated in this elderly population with
      invasive bladder cancer.

PMID- 19381078
TI  - Treatment of metastatic breast cancer: a large observational study on adherence
      to French prescribing guidelines and financial cost of the anti-HER2 antibody
      trastuzumab.
AB  - OBJECTIVE: This observational study aimed at analyzing adherence to prescribing
      guidelines of anti-HER2 monoclonal antibody trastuzumab treatment for metastatic
      breast cancer. Efficacy and costs were also evaluated. METHODS: The adherence to
      the trastuzumab treatment plan was analyzed according to both the French
      postlicensing guidelines published in 2001 and clinical guidelines from the
      regional cancer network in a cohort of 131 consecutive patients. RESULTS: The
      level of appropriateness to the molecular target was very high (92% of the
      patients showed a positive HER2 status, defined as HER2 3+ confirmed by
      immunohistochemistry or 2+ confirmed by fluorescent in situ hybridization). The
      treatment plan was made according to the French postlicensing guidelines in 41
      patients (31.3%) and to the regional clinical guidelines for 109 patients
      (83.2%). The main reason for the difference was the type of molecules authorized
      for combination to trastuzumab. The median overall survival of the studied
      population was 18.6 months and the median progression-free survival rate was 7.7
      months. Up to death or end of the study, the overall cost for the treatment of
      breast cancer with trastuzumab per patient and per year was 47,832 euro.
      CONCLUSION: This quite low adherence of clinicians to the French postlicensing
      guidelines is in contrast with the high level of adherence to the regional
      clinical guidelines. The reason is that the latter are less rigid about
      previously received treatments and enlarge the potential associated cytotoxics to
      vinorelbine. This supports the French National Cancer Institute decision to get
      expert clinicians involved together with the French agency for sanitary security
      of health products and the high health authority in a common elaboration of
      guidelines.

PMID- 19381081
TI  - Performance of a MedArray silicone hollow fiber oxygenator.
AB  - A silicone hollow fiber oxygenator was evaluated to characterize gas transfer and
      biocompatibility. The device's fiber bundle was composed of MedArray's silicone
      hollow fibers with a 320 microm outside diameter, a 50 microm wall thickness, a
      surface area of 0.45 m, and a 0.49 void fraction. An in vitro gas exchange study
      was performed comparing the MedArray device (n = 9) with the Medtronic 0600
      oxygenator (n = 6) using Association for the Advancement of Medical
      Instrumentation standards and blood flow rates of 0.5-1.75 L/min, and an oxygen
      to blood flow ratio of two. Biocompatibility and resistance studies were
      performed in vivo using a swine venovenous extracorporeal membrane oxygenation
      model (MedArray n = 5, Medtronic n = 5). Average O(2) transfer at 1 L/min was 86
      ml/min/m in the MedArray device and 101.1 ml/min/m in the Medtronic device. At
      0.5 L/min the MedArray and Medtronic device average resistance was 15.5 and 148.5
      mm Hg/(L/min), respectively. Both devices had similar platelet consumption and
      hemolysis. Results indicate that the MedArray device has lower O(2) transfer
      efficiency, similar biocompatibility, and lower resistance than the Medtronic
      0600 oxygenator. Optimization of the MedArray fiber bundle and housing design is
      necessary to improve O(2) transfer efficiency while maintaining lower device
      resistance than the Medtronic oxygenator.

PMID- 19381082
TI  - Design analysis and performance assessment of hybrid magnetic bearings for a
      rotary centrifugal blood pump.
AB  - A hybrid magnetic bearing system was designed for a rotary centrifugal blood pump
      being developed to provide long-term circulatory support for heart failure
      patients. This design consists of two compact bearings to suspend the rotor in
      five degrees-of-freedom with single axis active control. Permanent magnets are
      used to provide passive radial support and electromagnets to maintain axial
      stability of the rotor. Characteristics of the passive radial and active thrust
      magnetic bearing system were evaluated by the electromagnetic finite element
      analysis. A proportional-integral-derivative controller with force balance
      algorithm was implemented for closed loop control of the magnetic thrust bearing.
      The control position is continuously adjusted based on the electrical energy in
      the bearing coils, and thus passive magnetic forces carry static thrust loads to
      minimize the bearing current. Performance of the magnetic bearing system with
      associated control algorithm was evaluated at different operating conditions. The
      bearing current was significantly reduced with the force balance control method
      and the power consumption was below 0.5 W under various thrust loads. The bearing
      parameters predicted by the analysis were validated by the experimental data.

PMID- 19381083
TI  - Acute renal failure during extracorporeal support in the pediatric cardiac
      patient.
AB  - End-organ dysfunction is associated with increased mortality in pediatric cardiac
      patients requiring extracorporeal support. We sought to characterize the odds of
      developing acute renal failure (ARF) as well as associated increases in mortality
      in this population. Records of all cardiac patients in our pediatric intensive
      care unit receiving extracorporeal membrane oxygenation (ECMO) over a 24 month
      period were reviewed for data with respect to their course. Acute renal failure
      was defined as fluid retention or electrolyte disturbance resulting in
      institution of continuous renal replacement therapy (CRRT), or a glomerular
      filtration rate (GFR) of <35 ml/min/1.73 m. Analysis revealed 49 ECMO runs in 48
      patients, with ARF present in 71.7%, and CRRT initiated in 58.7%. Odds for
      developing ARF increased by 60% per day of ECMO support (beta 1.60, 95% CI 1.08
      2.37, p = 0.018). Acute renal failure during ECMO, after adjusting for patient
      age, remained associated with a decrease in odds of survival to discharge (OR
      4.7, 95% CI 1.10-20.4, p = 0.037). We conclude that ARF is more common among
      pediatric cardiac patients requiring extracorporeal support than previously
      recognized. Increasing duration of ECMO support is associated with development of
      ARF. Acute renal failure while on ECMO is associated with a significant decrease
      in the odds of survival in the pediatric cardiac patient.

PMID- 19381084
TI  - Hepatobiliary disease in patients with cystic fibrosis.
AB  - PURPOSE OF REVIEW: This review explores the recent advances in knowledge
      regarding hepatobiliary disease in patients with cystic fibrosis. RECENT
      FINDINGS: Hepatobiliary abnormalities associated with cystic fibrosis are varied
      in nature and range from defects attributable to the underlying genetic defect to
      those related to systemic disease and malnutrition. Novel research into the
      underlying pathogenesis of cystic fibrosis liver disease and the primary role of
      cystic fibrosis transmembrane conductance regulator in biliary secretory
      epithelium is presented. This work has been fostered by the development of new
      animal models of cystic fibrosis transmembrane conductance regulator dysfunction.
      Of the wide range of hepatobiliary complications associated with cystic fibrosis
      the most clinically relevant problem is progression of focal biliary cirrhosis to
      multilobular cirrhosis with its attendant complications of portal hypertension
      and potentially end-stage liver disease. However, recent studies suggest that
      liver transplantation may not improve survival in patients with cystic fibrosis
      and significant portal hypertension. SUMMARY: Hepatobiliary disease is a common
      finding in patients with cystic fibrosis; the pathogenesis is multifactorial in
      nature. As new therapeutic strategies emerge, life expectancy will continue to
      increase as will the impact of liver disease on quality of life and survival of
      patients with cystic fibrosis. This review will discuss novel insights into
      pathogenesis as well as diagnostic and management options.

PMID- 19381085
TI  - Cholangioscopy: where are we now?
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update on current
      technologies and clinical indications for cholangioscopy. The review also focuses
      on techniques, challenges and limitations of available devices. RECENT FINDINGS:
      Recent technological advances such as the introduction into clinical practice of
      video cholangioscopes as well as a single-operator semidisposable per oral
      cholangioscope are described. Novel clinical applications of cholangioscopy are
      also discussed. SUMMARY: The past several years have witnessed the emergence of
      new technologies, including video and semidisposable cholangioscopes, which have
      increased the availability and utilization of cholangioscopes. Although the most
      common indications for this technique remain investigation of indeterminate
      cholangiographic findings and management of large bile duct stones, technological
      advances in the devices and available accessories will invariably lead to
      expanded indications in the future.

PMID- 19381086
TI  - Clinical decision rules for evaluating meningitis in children.
AB  - PURPOSE OF REVIEW: Distinguishing between bacterial and aseptic meningitis in
      children is sometimes difficult. Guidelines recommend that patients with acute
      meningitis be systematically hospitalized and treated with antibiotics until the
      cerebrospinal fluid culture results are available. This strategy ensures rapid
      treatment for bacterial meningitis, but also involves unnecessary admissions and
      antibiotics for aseptic meningitis. Some authors have, therefore, proposed
      different combinations of predictors in clinical decision rules to distinguish as
      early as possible between bacterial and aseptic meningitis. To be useful, these
      rules must have near-100% sensitivity for bacterial meningitis, good specificity
      (to reduce unnecessary antibiotics and admissions), and easy bedside application.
      RECENT FINDINGS: The present review examines the performance and level of
      validation of decision rules proposed after the Haemophilus influenzae
      vaccination entered widespread use. Most of these rules have been validated
      incompletely, if at all. Only one rule incorporates the best single validated
      predictive marker for distinguishing between bacterial and aseptic meningitis in
      children: serum procalcitonin level. SUMMARY: Two rules are highly promising,
      meeting the three major conditions after a retrospective validation process in
      large samples. These rules can be applied cautiously to patients with the same
      inclusion and exclusion criteria as those in the derivation sets, while awaiting
      prospective multicenter validation studies.

PMID- 19381087
TI  - What predicts the change from episodic to chronic migraine?
AB  - PURPOSE OF REVIEW: Because migraine worsens in a sizeable subgroup of sufferers,
      but not in most, identifying factors that predict the change from episodic into
      chronic migraine is of extreme interest and should be seen as a priority in
      headache research. RECENT FINDINGS: Potentially remediable risk factors include
      frequency of migraine attacks, obesity, excessive use of medications containing
      opioids and barbiturates, caffeine overuse, stressful life events, depression,
      sleep disorders and cutaneous allodynia. SUMMARY: While we wait for evidence
      regarding the benefits of risk factor modifications in the prevention of chronic
      migraine, several interventions are justifiable based on their other established
      benefits. For example, decreasing headache frequency with behavioral and
      pharmacological interventions will decrease current disability even if it does
      not modify clinical course. Monitoring the body mass index and encouraging
      maintenance of normal body weight is good practice in patients with and without
      migraine. Avoiding overuse of caffeine is desirable apart from its potential
      benefit in preventing progression. Sleep problems should be investigated and
      treated. Psychiatric comorbidities should be identified and addressed.
      Medications containing opioids and barbiturates should be reserved for a few
      selected cases of migraine, and their use should be monitored. For these
      interventions, the possibility of preventing progression may motivate clinicians
      to offer good care and patients to engage in the treatment plan.

PMID- 19381088
TI  - Update on phototherapeutic keratectomy.
AB  - PURPOSE OF REVIEW: To review all recent publications on the use of
      phototherapeutic keratectomy (PTK). RECENT FINDINGS: Recent studies confirm the
      beneficial outcomes of PTK in a variety of anterior corneal disorder: anterior
      stromal scars, dystrophies of the corneal epithelium and the anterior stroma, and
      elevated corneal lesions. They also try to evaluate the biomechanical properties
      of eyes with granular corneal dystrophy undergoing PTK, in an effort to prevent
      iatrogenic ectasia. The different genotypes in patients with transforming growth
      factor, beta-induced linked corneal dystrophies have recently been correlated to
      the surgical outcome after PTK. An extensive review of recurrent corneal erosion
      syndrome identified PTK as the most effective treatment. In the developing world,
      the most common indication for PTK is still bullous keratopathy, as PTK can be
      successfully used while waiting for penetrating keratoplasty. SUMMARY: PTK can
      successfully treat a variety of conditions of the anterior cornea. New studies
      may further expand its use.

PMID- 19381089
TI  - Anti-vascular endothelial growth factor therapy for neovascular ocular diseases
      other than age-related macular degeneration.
AB  - PURPOSE OF REVIEW: Anti-vascular endothelial growth factor (anti-VEGF) therapies
      that arrest choroidal angiogenesis and reduce vascular permeability have
      revolutionized clinical practices for neovascular eye diseases. This review
      describes anti-VEGF strategies that are being evaluated in ocular diseases, other
      than neovascular age-related macular degeneration, in which neovascularization
      plays a critical role in pathogenesis. RECENT FINDINGS: Early studies of the anti
      VEGF agents, pegaptanib sodium, ranibizumab, bevacizumab, VEGF trap, and
      bevasiranib in the treatment of various neovascular diseases (e.g., diabetic
      macular edema, retinal vein occlusion, choroidal neovascularization) have shown
      promising results. The efficacy and safety of these agents, either alone or
      combined with standard treatments (e.g., laser photocoagulation), anti
      inflammatory agents, or other non-VEGF-based antiangiogenic therapies, is
      actively investigated. Non-VEGF-driven pathways and growth factors other than
      VEGF may play important roles in pathogenesis and are included in certain
      combination therapies with VEGF inhibitors. SUMMARY: The discovery of VEGF-A's
      role in the pathogenesis of neovascular ocular disease provided a strong
      rationale for the development of anti-VEGF-based therapies. There is now ample
      evidence that anti-VEGF therapies are viable treatment options for these
      diseases. Nevertheless, large, randomized controlled trials are still awaited to
      confirm early safety and efficacy findings from small, open-label prospective
      studies.

PMID- 19381090
TI  - The use of simulation for pediatric training and assessment.
AB  - PURPOSE OF REVIEW: Simulation has been widely adopted as a training and
      assessment tool in medical education. Conventional teaching methods may be
      inadequate to properly train healthcare providers for rare but potentially lethal
      events in pediatrics such as trauma and respiratory arrest. Recent studies
      suggest pediatric acute care providers have limited exposure to critically ill
      patients and also lack the skills to manage them. Simulation has the potential to
      fill this educational void. This review will highlight the role of simulation as
      an educational and assessment tool, with a particular emphasis on retention of
      knowledge and skills. RECENT FINDINGS: Simulation is currently used as an
      assessment tool to provide ongoing feedback during training (formative
      assessment) and is gaining popularity as an adjunctive method for demonstrating
      competency (summative assessment). Recent literature demonstrates increased
      retention of knowledge and skills after simulation-based training in the areas of
      resuscitation, trauma, airway management, procedural training, team training, and
      disaster management. SUMMARY: Simulation is an effective training tool for
      pediatric acute care providers. Further research is necessary to develop
      validated performance assessment tools and demonstrate improvement in clinical
      outcomes after simulation training.

PMID- 19381091
TI  - Recent advances in neuroblastoma.
AB  - PURPOSE OF REVIEW: Although there have been recent advances with multimodal
      therapy, treatment of neuroblastoma remains a clinical challenge. Despite the
      identification of several genetic features, there has not been a significant
      increase in 5-year survival in the last decade. This review will highlight the
      current operative strategies along with new research developments aimed at
      improving survival. RECENT FINDINGS: The goal of surgical intervention in the
      early stages of neuroblastoma is complete curative resection. In advanced-stage
      disease, tissue biopsy for staging is the initial goal. In recent years,
      minimally invasive surgery (MIS) is considered in carefully selected patients.
      Recent advances in neuroblastoma research have focused on tyrosine kinase
      inhibition, differentiation, pathway inhibition, and immunotherapy. Several of
      these targets have shown promising results in vivo and are currently under
      investigation for potential clinical trials. SUMMARY: New information on the
      importance of cell signaling and the targeting of specific genes of interest are
      providing key insights into neuroblastoma. Only through the discovery of novel
      treatment strategies made available through the advancement of research will
      neuroblastoma be survivable for patients with advanced-stage disease.

PMID- 19381092
TI  - Sedation for emergent diagnostic imaging studies in pediatric patients.
AB  - PURPOSE OF REVIEW: To review and summarize current literature regarding sedation
      for imaging studies in pediatric patients in the Emergency Department and acute
      care setting. RECENT FINDINGS: Multiple guidelines about preparation, monitoring,
      and appropriate training of personnel administering pediatric sedation have been
      published. Recommendations for fasting prior to sedation remain in flux. Agents
      such as chloral hydrate, barbiturates, and benzodiazepines that have been used
      for pediatric sedation for many years continue to be studied. These agents are
      compared with newer agents such as etomidate, propofol, and dexmedetomidine.
      SUMMARY: Although avoiding sedation for diagnostic imaging studies is optimal,
      there are multiple agents with reasonable safety profiles that can be utilized by
      personnel trained in pediatric airway management in order to obtain adequate
      emergent imaging studies.

PMID- 19381093
TI  - Antiemetics for acute gastroenteritis in children.
AB  - PURPOSE OF REVIEW: The alleviation of vomiting due to gastroenteritis in children
      can help promote oral rehydration and prevent medical visits for dehydration.
      RECENT FINDINGS: Recent randomized, placebo-controlled trials of newer
      antiemetics, such as serotonin antagonists like ondansetron, have demonstrated
      efficacy in relief of vomiting, decreased need for intravenous fluid therapy and
      hospitalizations, without serious adverse effects. SUMMARY: The ability to arrest
      further vomiting and prevent intravenous fluid therapy and hospitalization aids
      children with vomiting so they may tolerate oral fluids and be discharged from
      medical care. This can reduce the medical care burdens and enhance patient
      satisfaction. This new pharmaceutical therapy may change how gastroenteritis is
      managed as it is studied further.

PMID- 19381094
TI  - Facial pain: an update.
AB  - PURPOSE OF REVIEW: Review current literature in the field of chronic nondental
      facial pain as recent clinical research findings need to be put into practise.
      RECENT FINDINGS: The areas covered include epidemiology and risk factors for
      facial pain, management of temporomandibular disorders, burning mouth syndrome,
      atypical odontalgia and trigeminal neuralgia. SUMMARY: There is an increasing
      awareness that facial pain is common and has similar risk factors to other
      chronic pain conditions. Some oral pain conditions are now being recognized as
      being probably neuropathic in origin rather than being due to psychological
      factors. A more biopsychosocial approach to management of these conditions is
      essential. The first international guidelines on management of trigeminal
      neuralgia have now been published and should help all clinicians seeing these
      patients.

PMID- 19381095
TI  - Pulmonary rehabilitation for dyspnea in the palliative-care setting.
AB  - PURPOSE OF REVIEW: Although pulmonary rehabilitation has reproducibly improved
      dyspnea and quality of life indices in patients with chronic obstructive
      pulmonary disease (COPD), its suitability to the palliative-care setting is not
      well established. Evolutions in exercise design, self-monitored home-based
      programs, and understanding of the patient populations that may benefit are
      rendering pulmonary rehabilitation more feasible for patients with significant
      impairment. In this review, we focus on the recent developments that translate
      most successfully into the palliative-care setting. RECENT FINDINGS: Several
      lower intensity protocols--including interval training and single-leg ergometry-
      compare positively with the gold standard of high-intensity aerobic exercise in
      improving dyspnea and functional capacity. Passive strategies such as
      neuromuscular electrical stimulation have been demonstrated to improve muscle
      strength and mass and reduce exertional dyspnea. Home-based, self-monitored
      programs compare favorably with outpatient hospital-based programs. There is
      increasing evidence that pulmonary rehabilitation is well tolerated and effective
      for patients with severe COPD, and that other diseases associated with disabling
      dyspnea may improve symptomatically with pulmonary rehabilitation. SUMMARY:
      Recent innovations in pulmonary rehabilitation interventions and setting allow
      the flexibility to facilitate its incorporation into an individualized palliative
      plan of care. Appropriately tailored, pulmonary rehabilitation may provide
      additional opportunities to optimize functional capacity and reduce symptom
      burden.

PMID- 19381096
TI  - Octreotide for recurrent intestinal variceal bleeding in patients without portal
      hypertension.
AB  - We report on the efficacy of octreotide acetate in two patients with intestinal
      phlebectasia and no evidence of portal hypertension or mesenteric thrombosis.
      Patient 1 was a 46-year-old woman with primary pulmonary arterial hypertension.
      She required repeated transfusions for recurrent episodes of gastrointestinal
      bleeding (GIB). Intraoperative enteroscopy revealed wide-spread small bowel
      phlebectasia and intestinal resection was not performed. Blue rubber-bleb
      syndrome, portal hypertension and mesenteric thrombosis were ruled out.
      Octreotide acetate long-acting release was started. A transient interruption in
      treatment was followed by severe overt GIB. This was effectively controlled with
      continuous infusion of octreotide acetate. After this episode, octreotide acetate
      long-acting release was resumed and no further episodes of GIB have been reported
      until the most recent follow up (total duration of 74 months). Patient 2 was a 51
      year-old woman with a history of recurrent GIB requiring multiple blood
      transfusions since young adulthood with negative endoscopic investigations. An
      enteroscopy showed numerous submucosal serpiginous varices in the colon and the
      terminal ileum. All putative causes including portal hypertension or mesenteric
      thrombosis were ruled out. Monthly intramuscular injections of long-acting
      octreotide acetate were initiated, and no GIB occurred since then (27 months of
      follow up). Somatostatin analogues are known to reduce splanchnic blood flow, to
      increase vascular resistance, to enhance platelet aggregation; and are thus
      efficacious in preventing GIB secondary to various vascular lesions (portal
      hypertension, intestinal angiodysplasia and blue rubber-bleb syndrome). These
      case reports suggest that they are also effective in preventing GIB in intestinal
      phlebactasia without portal hypertension.

PMID- 19381097
TI  - Physiotherapy after stroke in Ireland: a qualitative insight into the patients'
      and physiotherapists' experience.
AB  - The study aimed to examine the experience of inpatient physiotherapy intervention
      delivered after stroke in Ireland from two different perspectives: that of the
      person with stroke and that of the physiotherapist. A qualitative study was
      conducted involving semi-structured interviews with 10 people with stroke and two
      focus groups with 10 senior physiotherapists working in the area of neurology.
      All transcriptions were analysed using the grounded theory approach. People with
      stroke and physiotherapists agreed that people with stroke could benefit from
      more physiotherapy than is routinely provided in the rehabilitation setting.
      However, the timing of the intervention was disputed. Family-mediated exercise
      therapy was identified as an acceptable adjunct to routine physiotherapy after
      stroke. People with stroke identified walking and lower-extremity exercises as
      the most important components of their programme. Furthermore, they identified
      honesty and encouragement as two important traits in a physiotherapist working
      with people with stroke. Obtaining the perspective of patients is an important
      and valuable way of evaluating healthcare services. Physiotherapists need to be
      cognizant of the elements of rehabilitation that are important to people with
      stroke. Methods of delivery of stroke care need to evolve and incorporate
      families not only for practical purposes but also from a psychological aspect.
      Family-assisted exercise therapy after stroke may enhance the carry-over outside
      formal physiotherapy, giving patients and their families the opportunity to
      maximize recovery.

PMID- 19381098
TI  - Higher dropout rate in non-native patients than in native patients in
      rehabilitation in The Netherlands.
AB  - Dropout from a rehabilitation programme often occurs in patients with chronic
      nonspecific low back pain of non-native origin. However, the exact dropout rate
      is not known. The objective of this study was to determine the difference in
      dropout rate between native and non-native patients with chronic nonspecific low
      back pain participating in a rehabilitation programme in The Netherlands. A
      retrospective study (n = 529) of patient files was performed in two
      rehabilitation centres and two rehabilitation departments of general hospitals in
      The Netherlands. Patient files were checked for diagnosis, status of origin, sex,
      age and outcome, that is, reason for finishing treatment. The difference in
      dropout rate between patients of Dutch and non-Dutch origin was tested by chi
      tests and logistic regression-analysis, controlling for age, sex, type of
      rehabilitation institute and phase of the rehabilitation programme. Dropout
      occurred among one fifth (18.7%) of the total patient population. Dropout among
      patients of non-Dutch origin was twice as high as among native Dutch patients (P
      < 0.001). In regression analyses dropout was related to status of non-Dutch
      origin, treatment in a rehabilitation centre and the diagnostic phase of a
      rehabilitation programme. In conclusion, patients of non-Dutch origin drop out
      considerably more frequently than native Dutch patients. Dropout is higher in the
      diagnostic phase than in the treatment phase and in rehabilitation centres than
      in hospitals. Future research should clarify the reasons for the high dropout
      rate in patients of non-native origin.

PMID- 19381099
TI  - Lopinavir/ritonavir in pregnancy.
AB  - OBJECTIVE: The Antiretroviral Pregnancy Registry was established in 1989 to
      collect data on birth defects after pregnancy exposures to antiretroviral
      therapy. Using Registry data, this study estimates the birth defect risk after
      pregnancy exposures to lopinavir/ritonavir. METHODS: The analysis population
      includes all prospective lopinavir/ritonavir-exposed pregnancies enrolled in the
      Registry from September 2000 through July 2007. Birth defect prevalence after
      pregnancy exposure is compared with rates from a population-based surveillance
      system, and first-trimester exposures are compared with combined second/third
      trimester exposures. RESULTS: Among 955 live births prenatally exposed to
      lopinavir/ritonavir, 23 cases with birth defects were reported [2.4%, 95%
      confidence interval (CI) = 1.5 to 3.6). Among 267 live births with first
      trimester exposures, 5 had birth defects (1.9%, 95% CI = 0.6 to 4.3). These rates
      are similar to the population-based comparator rate of 2.67% and the rate in
      infants with second/third-trimester exposures (2.6%, 95% CI = 1.6 to 4.1). No
      pattern of birth defects suggestive of a common etiology was seen. CONCLUSIONS:
      The prevalence of birth defects among infants prenatally exposed to
      lopinavir/ritonavir is not significantly different from internal or external
      comparison groups. These data provide reassuring information to patients and
      clinicians about the safety of lopinavir/ritonavir in the treatment of HIV
      positive pregnant women.

PMID- 19381100
TI  - BaS analysis: suggesting a new cephalometric model in follow-up of patients with
      craniostenosis who underwent craniofacial advancement surgery after 1 year from
      the end of the distraction protocol.
AB  - Evaluation of the relapse in patients with craniofacial malformation who
      underwent craniofacial advancement surgery is very difficult, and data are often
      unreliable. This is because common skeletal landmarks move from their original
      position, making standard cephalometries completely useless. To solve this
      problem, some authors proposed evaluations based on 2- and 3-dimensional computed
      tomographies, but the biologic risk and the economic outcome do not consent to
      repeat this kind of examination too often. In this paper, the authors propose a
      new cephalometric model based on the evaluation of facial skeletal landmarks on
      the BaS axis. This method, named BaS analysis, might be useful in evaluating
      improvements of the splanchnocranium in patients who underwent craniofacial
      advancement.

PMID- 19381101
TI  - On the origin of bitemporal hollowing.
AB  - INTRODUCTION: Long-term results after cranioplasty for trigonocephaly often show
      bitemporal hollowing and a residual hypotelorism. Both findings fuel the
      perception that the growth of the periorbital region and the forehead as a whole
      continues to be restricted, even after correction. The aim of this study was to
      evaluate the growth process of the periorbital region after correction for
      trigonocephaly in the long term. MATERIALS AND METHODS: From 1972 to 2004, 184
      patients underwent a cranioplasty for the correction of nonsyndromatic
      trigonocephaly. Cephalometric analysis was performed in 33 of these patients who
      had their radiographs taken on the same day as the photograph, at least 1 year
      postoperative and before the age of 6 years. Cephalic landmarks were used to
      analyze the growth of the forehead. Because of the lack of standardized
      cephalograms, growth ratios were used instead of absolute measurements. For
      visual analysis, normal anteroposterior photographs were used, which were taken
      on the same day as the radiograph. Two observers evaluated the anteroposterior
      photographs for the presence and level of temporal hollowing. A score of 0
      (normal), 1 (moderate deformity), or 2 (severe deformity) was assigned to each of
      the photographs. RESULTS: A significant relation was found between a severe
      deformation seen at postoperative photographic evaluation and a lower growth
      ratio. The preoperative photo score was not of predicting value for the
      postoperative growth ratio and therefore, indirectly, for the postoperative photo
      score. The mean preoperative photo score dropped 5% after surgery. The age at
      operation had no influence on this postoperative photo score. The experience of
      the surgeon, however, was a significant contributing factor. CONCLUSIONS:
      Temporal hollowing seems to be of bony origin and can be explained by skeletal
      growth inhibition in the affected area. When present immediately after operation,
      they seem to persist through the years, which makes surgical skill another factor
      of importance.

PMID- 19381102
TI  - Recurrent craniofacial dermatofibrosarcoma protuberans: long-term prognosis after
      close surgical removal.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant neoplasm of the
      dermis that rarely manifests in the craniofacial area. In this retrospective
      analysis, we investigated the long-term survival of 7 patients with recurrent
      craniofacial DFSP. This study includes all patients in our department with
      recurrences of DFSP between 1989 and 2006. All patients were treated by radical
      surgery with 1-cm free safety margin in every direction and remained in routine
      long-term follow-up for tumor patients. Two of the 7 patients showed a local
      recurrence, which was again successfully treated surgically with the same
      technique. Advanced reconstruction with free full-thickness skin transfers,
      regional flaps, and forearm flaps, respectively, was required in 5 of the 7
      patients. The other 2 patients were reconstructed locally. The long-term
      prognosis of craniofacial DFSP can be assessed optimistically even if the tumor
      already reoccurred. All 7 patients included in this study are still alive and so
      far not suffering from local recurrence. Advanced reconstructive techniques are
      often required in the management of reoccurring craniofacial DFSP. Late
      recurrences have been reported; therefore, a long-term follow-up for these
      patients should be considered.

PMID- 19381103
TI  - Photoelastic analysis of stress distribution in different retention systems for
      facial prosthesis.
AB  - The aim of this study was to assess the behavior and stress distribution of 3
      retention systems associated with implant for facial prosthesis by using the
      photoelasticity method. A photoelastic model was made from the replica of the
      orbital region on the left side of a dry skull with two 4-mm implants fixed in
      the superior orbital region. Three facial prosthetic retention systems were made
      for this study: O'ring, bar-clip, and magnets. The set (model/retention
      systems/prosthesis) was placed in a polariscope, and then traction began to be
      applied to the retention systems. The limit values for removal of the retention
      system were obtained by tests performed in an EMIC Universal test machine. The
      results were obtained by observation during the experiments and by photographic
      record of the stress behavior in the photoelastic model, resulting from the
      traction of the retention systems. In the magnet system, a lowest formation of
      fringes was verified both around and between the implants; in the O'ring system,
      the formation of photoelastic fringes was noted between the implants in the
      apical region; and in the bar-clip system, there was a greater concentration of
      colored fringes in the regions between the implants and cervical area. Based on
      the results obtained, it was concluded that the retention systems produced
      different stress distribution characteristics that, in general, were concentrated
      in the area around the implants, and the highest concentration of fringes, in
      increasing order, occurred in the retention systems of the magnets, O'ring, and
      bar-clip.

PMID- 19381104
TI  - Ultralong pedicled superficial temporal fascia island flaps for lower nasal
      defect.
AB  - OBJECTIVE: To explore the method of repairing nose defects of the apex, ala,
      septum, and even opposite ala nasi with ultralong pedicled superficial temporal
      fascia (STF) island flaps. METHODS: There were 29 cases of defects of the apex
      nasi, ala nasi, and nasal columella that were reconstructed, of which 12 cases
      were repaired with frontal-branched STF island flaps, 14 cases with apical
      branched STF postauricular island flaps, and 3 cases with prefabricated apical
      branched STF postauricular island flaps. The flap areas were arranged from 1.2 x
      2.3 to 2.0 x 2.8 cm2, the length more than 15 cm on average. Liners were
      reconstructed at the stage of the prefabricating flaps, with free skin graft in
      the cases of the alae nasi defects. The surfaces of the wound after flap
      prefabrications were covered by skin graft as well. RESULT: Twenty-seven cases
      were successfully taken without blood circulation blocks; the color, texture, and
      figure were good, and the outcomes were satisfying. Seven nonprefabricated flap
      cases have epidermis necrosis due to the lack of artery perfusion pressure and
      venous return handicap, and the epidermis fall off after 1 month; 2 cases of
      which required secondary surgeries because of partial necrosis. CONCLUSIONS: An
      ultralong pedicled STF island flap is an available way to repair defects of the
      apex nasi, ala nasi, and nasal columella. The benefits of a prefabricated flap
      are good blood circulation, primary made liner, and minute injury of the donor
      site. It is a good method of repairing defects of the apex nasi, ala nasi, nasal
      septum, and opposite ala nasi simultaneously.

PMID- 19381105
TI  - Treatment and outcome of advanced external auditory canal and middle ear squamous
      cell carcinoma.
AB  - This is a retrospective study to evaluate the outcomes and complications of
      combined treatment, surgery with or without adjunctive intraoperative
      radiotherapy, of locally advanced temporal bone squamous cell carcinoma. A series
      of 17 patients with locally advanced squamous cell carcinoma of the temporal bone
      were treated between September 2002 and February 2007. Eleven patients had
      primary tumors, and 6 patients had recurrences. According to the University of
      Pittsburgh staging system, 5 patients were stage II (T2 N0), 6 patients were
      stage III (5, T3 N0 and 1, T1 N1), and 6 patients were stage IV (5, T3 N2b and 1,
      T4 N0). All patients underwent lateral temporal bone resection and pedicle flap
      reconstruction. Eight patients received intraoperative and postoperative
      radiotherapies, 4 patients underwent postoperative radiation alone, whereas 5
      patients did not receive any adjunctive treatment. Median follow-up was 29.5
      months. No major complications were observed. No patients were found to have
      residual gross tumor. Disease-free survival was 73.3%, and overall survival was
      75.6%. Radical external auditory canal and/or middle ear canal resection is of
      utmost importance to obtain a good surgical outcome. Postoperative radiotherapy
      is necessary to obtain good local control; no major adverse effects were observed
      in the intraoperative radiotherapy patients. The incidence of major complication
      is minimal after pedicle flap reconstruction.

PMID- 19381106
TI  - Eplerenone does not attenuate diabetes-associated atherosclerosis.
AB  - BACKGROUND: It has been suggested that aldosterone, with its known pro
      inflammatory and profibrotic actions, may play a key role in the development and
      progression of atherosclerosis. METHOD: In this study, the ability of aldosterone
      antagonism to reduce atherosclerosis in experimental diabetes was assessed.
      Diabetes was induced in ApoE knockout mice with streptozotocin, and the mice were
      treated with the specific aldosterone antagonist, eplerenone, in their feed over
      20 weeks (approximately 200 mg/kg per day). RESULT: En face analysis revealed
      that eplerenone treatment was unable to attenuate atherosclerosis as assessed by
      percentage lesion area quantitation in the aortae of these mice compared with
      untreated diabetic mice (diabetic, 10.7 +/- 1.1; diabetic + eplerenone, 8.8 +/-
      1.2%). In contrast, we observed a significant, more than 50% decrease in
      percentage of plaque area in the nondiabetic control groups. Despite this lack of
      effect in the diabetic mice, eplerenone treatment was associated with reduced
      cytosolic superoxide production. However, aortic transcript levels of key
      molecules implicated in diabetes-associated atherogenesis, such as monocyte
      chemoattractant protein-1 and vascular cell adhesion molecule-1, were not
      significantly attenuated by eplerenone. CONCLUSION: These findings suggest that
      eplerenone treatment may not be as antiatherosclerotic in the diabetic context.

PMID- 19381107
TI  - When should antihypertensive drug treatment be initiated and to what levels
      should systolic blood pressure be lowered? A critical reappraisal.
AB  - The evidence for two recommendations of all major guidelines on hypertension is
      critically discussed. The first recommendation is that of initiating
      antihypertensive drug treatment when systolic blood pressure is at least 140 or
      diastolic blood pressure at least 90 mmHg in patients with grade 1 hypertension
      and low or moderate total cardiovascular risk, and even when blood pressure is in
      the high normal range in patients with diabetes and previous cardiovascular
      disease. The second recommendation is that of achieving systolic blood pressure
      levels below 140 mmHg in all hypertensive patients, including the elderly, and
      values below 130 mmHg in patients having diabetes and high/very-high-risk
      patients. Critical analyses of the results of available trials show that the
      evidence is scanty for both recommendations. Nonetheless, they can be accepted as
      prudent statements, as antihypertensive agents are very well tolerated and
      lowering systolic blood pressure below 130 mmHg appears well tolerated. However,
      wisdom should not be taken for evidence, and simple trials should be designed to
      look for more solid evidence in favour of current recommendations.

PMID- 19381109
TI  - The adverse prognostic significance of the metabolic syndrome with and without
      hypertension in patients who underwent complete coronary revascularization.
AB  - OBJECTIVES: The metabolic syndrome is associated with high risk for long-term
      coronary artery disease mortality. However, few studies have examined the
      prognostic importance of the metabolic syndrome with and without hypertension.
      METHODS: The data of 1133 nondiabetic patients who underwent complete
      revascularization were analyzed. The patients were categorized by the presence of
      the metabolic syndrome using the modified American Heart Association/National
      Heart, Lung, and Blood Institute statement and by the presence of hypertension.
      All patients were divided into four groups: neither the metabolic syndrome nor
      hypertension (group 1); the metabolic syndrome without hypertension (group 2);
      hypertension without the metabolic syndrome (group 3); and both the metabolic
      syndrome and hypertension (group 4). Cox proportional hazards were used in
      adjusted analyses for all-cause and cardiac mortality, as well as for the
      composite incidence of fatal and nonfatal stroke. RESULTS: The progress of 276
      (24.4%) patients in group 1, 413 (36.5%) in group 2, 105 (9.3%) in group 3, and
      339 (29.9%) in group 4 was analyzed. The mean follow-up was 10.4 +/- 3.4 years.
      Patients in group 4 had a higher risk of all-cause mortality (hazard ratio 1.78,
      P = 0.004). In addition, patients in groups 2 and 4 had a higher risk of cardiac
      mortality (group 2: hazard ratio 2.84, P = 0.04, group 4: hazard ratio 3.91, P =
      0.001) and stroke (group 2: hazard ratio 2.46, P = 0.03, group 4: hazard ratio
      2.09, P = 0.03). CONCLUSION: The metabolic syndrome both with and without
      hypertension is associated with increased risk of cardiac mortality and stroke
      incidence in patients who underwent complete coronary revascularization.

PMID- 19381108
TI  - Angiotensin II receptor blockers and myocardial infarction: an updated analysis
      of randomized clinical trials.
AB  - OBJECTIVE: To evaluate the effects of treatments based on angiotensin II receptor
      blockers (ARBs) on the risk of myocardial infarction (MI), cardiovascular and all
      cause death, as compared with conventional treatment or placebo. METHODS: We
      performed a meta-analysis of all available major international, randomized
      clinical trials (20 trials, n = 108 909 patients, mean age 66.5 +/- 4.1 years),
      published by 31 August 2008, comparing ARBs with other drugs or conventional
      therapies (placebo) and reporting MI incidence. RESULTS: During a mean follow-up
      of 3.3 +/- 1.1 years, a total of 2374/53 208 and 2354/53 153 cases of MI were
      recorded in ARB-based groups and in comparator arms, respectively [odds ratio
      (OR) 95% confidence interval (CI) 1.008 (0.950-1.069)]. Risks of MI were not
      different when tested in different clinical conditions, including hypertension,
      high cardiovascular risk, stroke, coronary disease, renal disease and heart
      failure. No significant differences in the risk of MI between treatment with ARBs
      versus placebo [OR 95% CI 0.944 (0.841-1.060)], beta-blockers and diuretics [OR
      95% CI 0.970 (0.804-1.170)], calcium channel blockers [OR 95% CI 1.112 (0.971
      1.272)], or angiotensin-converting enzyme (ACE) inhibitors [OR 95% CI 1.008
      (0.926-1.099)] were observed. Analysis of trials comparing combination therapy
      based on ARBs plus ACE inhibitors versus active treatments or placebo showed
      equivalent MI risk [OR 95% CI 0.996 (0.896-1.107)]. CONCLUSION: The present meta
      analysis indicates that the risk of MI is comparable with use of ARBs and other
      antihypertensive drugs in a wide range of clinical conditions.

PMID- 19381110
TI  - The development of patient safety in Turkey: constraints and limitations.
AB  - Patient safety is a complex multifaceted issue linked with quality management.
      Evidence reveals that nurses are pivotal to the success of quality management and
      patient safety initiatives. There are many studies about patient safety in
      developed countries, but less is known about nursing care and patient safety in
      developing or mid-level economies such as Turkey. The aim of this paper is to
      discuss the quality management and patient safety developments in the Turkish
      healthcare sector.

PMID- 19381111
TI  - Providing a healthy work environment for nurses: the influence on retention.
AB  - Differences in registered nurses' (RNs) perceptions of their work environment
      were measured with the Insel and Moos' Work Environment Scale to identify factors
      in the work environment that may influence retention. Statistically significant
      differences for perceptions of supervisor support and innovation were found
      between those RNs who left their unit or hospital during a 24-month period and
      those who stayed. Implementing strategies to promote retention of RNs to ensure
      safe, quality patient care is essential.

PMID- 19381112
TI  - AUA and WOCN Society joint position statement on the value of preoperative stoma
      marking for patients undergoing creation of an incontinent urostomy.

PMID- 19381113
TI  - Cutaneous melanoma in the elderly.
AB  - The aim of this review was to analyze the difficulties in diagnosing and treating
      elderly patients with cutaneous melanoma. It focused on the main causes for late
      diagnosis and relatively poor prognosis in these patients. Early detection of
      melanoma is vital to reduce mortality in these patients and surgery is often
      curative. Adequate treatment of elderly patients with melanoma requires knowledge
      of the clinical features and histopathology of the disease, and the therapeutic
      options. This review also examined the main surgical procedures for primary
      melanoma and regional lymph node staging, and the curative and palliative
      procedures indicated for those elderly patients with advanced disease. It is
      expected that several molecular genetic factors will soon provide further
      prognostic information of possible benefit for elderly patients with melanoma.

PMID- 19381114
TI  - Feedback-related negativity effects vanished with false or monetary loss choice.
AB  - Feedback-related negativity (FRN) is sensitive to both monetary loss and
      evaluation of the correctness of a response. This study used a gambling task that
      required participants to choose between two cards that were unpredictably
      associated with monetary gains or losses. Feedback stimuli then indicated gain or
      loss, and the correctness of the participant's choice. Greater FRN amplitudes for
      loss versus gain conditions were observed when participants guessed correctly, as
      well as for incorrect versus correct conditions when they made gain choices.
      Conversely, FRN effects were absent after either false choices or those that led
      to losses. Therefore, FRN may reflect an interaction between guess correctness
      and the utilitarian value of feedback.

PMID- 19381115
TI  - Assessment of dual-time-point 18F-FDG-PET imaging for pulmonary lesions.
AB  - OBJECTIVE: The objective of this study was to assess suitability of dual-time
      point 18F-FDG [(18F)-fluoro-2-deoxyglucose]-PET imaging for differentiating
      between malignant and benign pulmonary lesions, whose size and maximal
      standardized uptake values (SUVs) are greater than 10 mm and 2.5, respectively.
      METHODS: A total of 38 patients, 27 with malignant lesions (n = 30), and 11 with
      benign lesions (n = 22), were investigated by performing two static acquisitions
      started at mean times t = 79 and t = 158 min after the tracer injection. A model
      analysis involving tissue 18F-FDG uptake and release has been developed and
      applied. RESULTS: Malignant lesions showed a SUV increase between the two
      acquisitions for 27 of 30 lesions, and a SUV decrease or constancy for the other
      three. Benign lesions showed a SUV increase in 19 of 22 lesions, and a SUV
      decrease in three (both increase and decrease were observed for multiple benign
      lesions in two patients). CONCLUSION: It is recommended that dual-time-point 18F
      FDG-PET imaging is not indicated to differentiate between malignant and benign
      pulmonary lesions, whose size and maximal SUV are greater than 10 mm and 2.5,
      respectively. Furthermore, a model analysis suggests that the variation in SUV
      observed between early and delayed scans may be explained by different values of
      the 18F-FDG release/uptake ratio.

PMID- 19381116
TI  - Radioiodine therapy for thyroid volume reduction of large goitres.
AB  - OBJECTIVE: To evaluate the effect of radioiodine therapy for volume reduction in
      large goitres. METHODS: A retrospective study was performed involving 88 patients
      treated between 2001 and 2007 with radioiodine for toxic or nontoxic goitres. The
      goitres were between 80 and 250 ml in volume (median 127 ml+/-38.57). Activities
      of I to be administered were calculated individually through radioiodine testing
      with uptake measurements over 5 days, the mean activity being 1721+/-440 MBq I
      (714-2395 MBq I), equivalent to a mean of 14+/-4.19 MBq I/g of thyroid tissue (6
      24 MBq I/g of thyroid tissue). The designated dose was 150 Gy for the entire
      thyroid volume, and post-therapeutic dosimetry revealed a mean thyroid dose of
      175+/-45.92 Gy (64-300 Gy). Control examinations were performed, including
      thyroid blood testing and thyroid ultrasound at 6 weeks and at 3, 6, 12, 24, 36,
      48 and 72 months after radioiodine therapy. RESULTS: The mean volume reduction
      was 41.9% after 3 months and 65.9% after 1 year. Thyroid volume reduction was
      highly significant (P<0.001) in the first year after radioiodine therapy. No
      volume increase was observed in any patient during follow-up. Unfortunately, many
      patients were lost during follow-up (n = 84 after 3 months, n = 38 after 1 year).
      CONCLUSION: Radioiodine therapy is an effective treatment for both nontoxic and
      toxic goitres, resulting in a highly significant thyroid volume reduction of
      nearly 66% within 1 year.

PMID- 19381117
TI  - Non alcoholic fatty liver disease.

PMID- 19381118
TI  - Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD).
AB  - The authors summarize and update the most recent knowledge in the field of
      prevalence, natural history and incidence of Non Alcoholic Fatty Liver Disease
      (NAFLD) and Non Alcoholic Steatohepatitis (NASH). These novel diseases, firstly
      recognized at the beginning of the second millennium, arose suddenly to the
      attention of the clinicians, because they are the hepatic expression of the "so
      called" metabolic syndrome. Due to the epidemic burden of obesity, diabetes, and
      metabolic diseases, NAFLD and NASH will become soon probably the most common
      hepatic disease worldwide, and they surely will keep busy our future young
      hepatologists.

PMID- 19381119
TI  - New insights into the pathophysiology of nonalcoholic fatty liver disease.
AB  - The consequences of pathologic adipose tissue accumulation have been described
      for almost all organs. Nonalcoholic fatty liver disease (NAFLD) is considered the
      most relevant hepatic manifestation of obesity. There is great interest in the
      study of NAFLD, and new insights into its pathogenic process have been described.
      Currently, in addition to insulin resistance, which was considered the hallmark
      of this disease, endocrine, immunologic, and central nervous system factors are
      attracting interest as explanatory variables. In this review, new factors
      associated with the main theories on the pathophysiology of NAFLD are analyzed.

PMID- 19381120
TI  - Metabolic syndrome and non-alcoholic fatty liver disease.
AB  - The development of nonalcoholic fatty liver disease (NAFLD) is strongly
      associated with the metabolic syndrome as reflected by the fact that
      approximately 90% of the patients with NAFLD have more than one feature of
      metabolic syndrome and about 33% have three or more criteria. The
      physiopathology, epidemiology and therapeutic considerations of the disease are
      reviewed here. Lipotoxicity plays a predominant role in the pathophysiology of
      both entities. It leads to accumulation of triglycerides in the liver as a result
      of an imbalance among the uptake, synthesis, export, and oxidation of fatty
      acids. Both conditions are very common in Mexico. Using the Adult Treatment Panel
      diagnostic criteria, the 1994 prevalence of the metabolic syndrome was
      26.6%.Although the prevalence of NAFLD is not known, but it can be estimated from
      the prevalence of obesity (30%). Since NAFLD is found in over two thirds of the
      obese subjects, this condition may exist in 20% of the adult population. The
      treatment of both conditions should be based in an integral approach, including
      the adoption of a healthy lifestyle, weight loss and may be pharmacotherapy. In
      summary, NAFLD is the hepatic expression of the metabolic syndrome. The study and
      treatment of these disorders could not be viewed as separate issues.

PMID- 19381121
TI  - Noninvasive diagnosis of nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic
      liver disease, affecting approximately 30% of Western populations and a frequent
      indication for liver transplantation. The histologic spectrum of NAFLD includes
      simple steatosis, which has a benign prognosis, and nonalcoholic steatohepatitis,
      a more aggressive form of liver injury that may progress to cirrhosis and its
      complications. At present, the only widely accepted means of differentiating
      these lesions, including the severity of hepatic fibrosis, is liver biopsy.
      However, due to the invasiveness of this procedure, the rising prevalence of
      NAFLD, and the expected availability of effective therapies for this condition,
      the identification of noninvasive tools for the diagnosis and staging of NAFLD
      has emerged as a major clinical and research priority. This review summarizes
      important advances in this field during the past decade, including the
      development of biomarkers of hepatic fibrosis, apoptosis, and inflammation; novel
      imaging techniques such as transient elastography; and high-throughput
      technologies including proteomics and genomics. Future studies must focus on the
      development of accurate, inexpensive, and reliable tools that can differentiate
      the major histologic determinants of NAFLD; are responsive to changes in NAFLD
      severity due to therapeutic intervention and time; and have prognostic
      significance. Until such tools are developed, liver biopsy remains an important
      tool in the assessment of patients with NAFLD.

PMID- 19381122
TI  - Role of nonalcoholic fatty liver disease in hepatocellular carcinoma.
AB  - Obesity and related disorders are a common cause of morbidity worldwide.
      Nonalcoholic fatty liver disease is the most important hepatic consequence of
      adipose accumulation. There is strong evidence of obesity-related disorders as
      risk factors for hepatocellular carcinoma and of nonalcoholic fatty liver disease
      as a cause of hepatocellular carcinoma, but it is apparently less important than
      other chronic liver diseases. Unfortunately, preventive measures are not well
      validated in the population of patients with NAFLD. In this review, we analyze
      the available information supporting the increased risk of hepatocellular
      carcinoma in obese patients and patients with nonalcoholic fatty liver disease,
      considering the epidemiological and basic research-derived evidence.

PMID- 19381123
TI  - Nonalcoholic fatty liver disease and its association with cardiovascular disease.
AB  - An association between non-alcoholic fatty liver disease (NAFLD) and
      cardiovascular disease (CVD) has been recently suggested. Indeed, different
      studies have demonstrated that NAFLD patients present increased subclinical
      atherosclerosis compared to non-steatosic individuals, and are supported by the
      few follow-up studies revealing that CVD is the second most common cause of death
      in NAFLD patients. However, the nature of the relationship NAFLD/CVD is still
      under debate.

PMID- 19381124
TI  - Association between type two diabetes and non-alcoholic fatty liver disease in
      youth.
AB  - In the last three decades prevalence of insulin related diseases has been growing
      worldwide with epidemic obesity, type 2 diabetes mellitus and non alcoholic fatty
      liver disease. In children such epidemics are particularly worrisome, since
      metabolic abnormalities track to the adulthood with significant implications for
      the health care system. Epidemiological studies support a close association
      between type 2 diabetes and fatty liver disease. We review the most recent
      epidemiological data on prevalence of both diseases in youth and their
      association.

PMID- 19381125
TI  - Treatment regimens for non-alcoholic fatty liver disease.
AB  - With the growing epidemic of obesity and diabetes, more attention has been placed
      on metabolic syndrome and its associated hepatic manifestation, non-alcoholic
      fatty liver disease (NAFLD). Within the spectrum of clinico-pathologic conditions
      known as NAFLD, only a minority of patients has the histological features
      characteristic of non-alcoholic steatohepatitis (NASH), which has the potential
      to progress to cirrhosis and hepatocellular carcinoma. Therefore, diagnosis and
      therapy should target patients with NASH. Current treatment recommendations
      include weight loss and the reversal of other components of metabolic syndrome,
      but several other treatment modalities are under investigation. To date, no
      pharmacologic treatment has been reliably shown to be effective for NASH. This
      article reviews all available treatment modalities, including lifestyle changes,
      bariatric surgery, weight loss medications, insulin sensitizers, lipid lowering
      agents, antioxidants, cytoprotective agents, and other novel treatments.

PMID- 19381126
TI  - Is exercise an effective treatment for NASH? Knowns and unknowns.
AB  - Non-alcoholic steatohepatitis has emerged as one of the most common causes of
      chronic liver disease in many regions of the world. Exercise and dietary changes
      constitute cornerstones of overall therapy aimed at achieving weight loss in
      hopes of ameliorating lipid-induced hepatocellular injury by mobilizing fat out
      of the liver. Indeed weight loss is known to be effective as evident in several
      controlled trials and, in the extreme, with bariatric surgery. However, less is
      known about exercise in the absence of weight loss especially in terms of
      altering hepatic fat metabolism. As with steatosis, adipose tissue function and
      other targets of insulin activity, skeletal muscle physiology is closely
      integrated with overall energy homeostasis and calorie disposal. Although much
      remains to be learned, increased physical conditioning appears to be closely
      linked to improved hepatic metabolism independent of changes in body weight. This
      is of practical importance to patients attempting lifestyle changes who may
      become unnecessarily discouraged if there is not evidence of associated weight
      loss as a result of increased activity. Moreover, the degree of physical
      conditioning represents an unmeasured and potentially confounding variable in
      most clinical trials of pharmacological intervention in NASH. Clinical
      investigation is needed to better understand the effects of exercise on liver fat
      metabolism and on how best to measure the degree of physical conditioning both as
      a baseline indicator of overall energy homeostasis and an end-point of treatment.

PMID- 19381127
TI  - Insulin resistance and steatosis in chronic hepatitis C.
AB  - In chronic hepatitis C, insulin resistance (IR) and type 2 diabetes mellitus (DM)
      are more prevalent than in healthy controls or in chronic hepatitis B patients.
      HCV infection promotes IR mainly through increased TNF-a and cytokine suppressor
      (SOCS-3) production. Both events inhibit insulin receptor and IRS-1 (insulin
      receptor substrate) tyrosine phosphorylation. Hepatic steatosis is also 2.5 fold
      more frequent in hepatitis C virus (HCV) infected patients as compared to the
      general population. Metabolic factors play a crucial role in the etiology of
      hepatic steatosis genotype non-3 related, which are also the genotypes with a
      greater association to IR. However, genotype 3, and particularly 3a, has a
      greater direct steatogenic capacity, and consequently, in those patients, the
      association with metabolic factors is weaker. Instead, in genotype 3, steatosis
      associates with viral factors like viral load. Those metabolic factors influence
      not only the natural history of HCV infection, as well as associate to an
      accelerated hepatic fibrosis progression, to a worse prognosis when hepatic
      cirrhosis is present, namely an increased risk of hepatocellular carcinoma, and
      to a lower sustained viral response rate. On the other hand, in patients who
      achieve viral eradication, IR and hepatic steatosis may regress, and return if
      viral infection recurs, which once again indicates an intrinsic steatosis and IR
      promoter action by HCV.

PMID- 19381128
TI  - Verbal intelligence in Neglect: the role of anosognosia for hemiplegia.
AB  - AIM: General intelligence of patients with neglect has been poorly investigated
      and data at present are contrasting. Moreover it is not yet defined whether the
      presence of anosognosia for hemiplegia is associated with intellectual impairment
      in patients with neglect. METHODS: In this prospective study the authors
      evaluated the verbal intelligence quotient in neglect patients. This study was
      carried out on 33 patients with left hemiparesis: 11 patients had neglect (group
      N), 11 had neglect + anosognosia (group N+A) and 11 had neither neglect nor
      anosognosia (control group). RESULTS: Patients of group neglect + anosognosia had
      significantly lower verbal IQ (VIQ) and mini-mental state examination (MMSE)
      scores than those of neglect (respectively: P=0.004 and P=0.000) and control
      groups (respectively: P=0.041 and P=0.000). No significant differences were
      detected between neglect and control groups for VIQ and MMSE. In N+A group VIQ
      score was lower than 90 in 81.8% and MMSE score was lower than 24 in 100% of
      patients. Moreover, 18.2% of N+A patients had VIQ score lower than 80 and 45.4%
      had MMSE score lower than 18/30. Also 9.1% of neglect group had VIQ score lower
      than 90 and 36.4% MMSE scores less than 24/30, but none of these patients had VIQ
      and MMSE scores respectively lower than 80 and 18/30. Similar data were present
      in control group. CONCLUSIONS: This study focuses on mental impairment in neglect
      + anosognosia patients and indicates that A for hemiplegia is a condition that
      more often occurs when severe mental impairment is present.

PMID- 19381129
TI  - Micro-drive array for chronic in vivo recording: drive fabrication.
AB  - Chronic recording of large populations of neurons is a valuable technique for
      studying the function of neuronal circuits in awake behaving rats. Lightweight
      recording devices carrying a high density array of tetrodes allow for the
      simultaneous monitoring of the activity of tens to hundreds of individual
      neurons. Here we describe a protocol for the fabrication of a micro-drive array
      with twenty one independently movable micro-drives. This device has been used
      successfully to record from hippocampal and cortical neurons in our lab. We show
      how to prepare a custom designed, 3-D printed plastic base that will hold the
      micro-drives. We demonstrate how to construct the individual micro-drives and how
      to assemble the complete micro-drive array. Further preparation of the drive
      array for surgical implantation, such as the fabrication of tetrodes, loading of
      tetrodes into the drive array and gold-plating, is covered in a subsequent video
      article.

PMID- 19381131
TI  - Functional evaluation of pallid mice with genetic emphysema.
AB  - Studies on pallid mice models of genetic emphysema have conventionally focused on
      morphological or biochemical evaluations. However, it is important to consider
      the functional aspects. We evaluated the exercise capacity and respiratory
      function in male pallid mice and male C57BL/6J mice at 3, 6, 12, and 15 months of
      age. The functional evaluations were conducted using a treadmill and a pulmonary
      function analysis device. The morphology of the lungs was analyzed on the basis
      of mean linear intercept (Lm) values. The body weights of the pallid mice at 12
      and 15 months were significantly lower than those of the age-matched C57BL/6J
      mice. The pallid mice showed deterioration in exercise capacity from 6 months, as
      indicated by the trends in running distance. At 6, 12, and 15 months, the pallid
      mice showed significantly higher pulmonary compliance and significantly lower
      forced expiratory volume in 20 ms (FEV(20 ms))/vital capacity (VC) values in
      comparison with the corresponding values for the C57BL/6J mice. In the
      morphological analysis of the pallid mice, emphysema was detected from 12 months,
      and the mice showed a significantly larger Lm at 12 months. The exercise capacity
      and lung function in the pallid mice significantly deteriorated from 6 months, at
      which time no pathological changes in the lung were detected. The deterioration
      in the exercise capacity and pulmonary function preceded the microscopic
      morphological changes.

PMID- 19381130
TI  - Alteration of the PKC-mediated signaling pathway for smooth muscle contraction in
      obstruction-induced hypertrophy of the urinary bladder.
AB  - Normal urinary bladder function requires contraction and relaxation of the
      detrusor smooth muscle (DSM). The DSM undergoes compensatory hypertrophy in
      response to partial bladder outlet obstruction (PBOO) in both men and animal
      models. Following bladder hypertrophy, the bladder either retains its normal
      function (compensated) or becomes dysfunctional (decompensated) with increased
      voiding frequency and decreased void volume. We analyzed the contractile
      characteristics of DSM in a rabbit model of PBOO. The protein kinase C (PKC)
      agonist phorbol 12, 13-dibutyrate (PDBu) elicited similar levels of contraction
      of DSM strips from normal and compensated bladders. However, PDBu-induced
      contraction decreased significantly in DSM strips from decompensated bladders.
      The expression and activity of PKC-alpha were also lowest in decompensated
      bladders. The PKC-specific inhibitor bisindolylmaleimide-1 (Bis) blocked PDBu
      induced contraction and PKC activity in all three groups. Moreover, the
      phosphorylation of the phosphoprotein inhibitor CPI-17 (a 17-kDa PKC-potentiated
      inhibitory protein of protein phosphatase-1) was diminished in DSM from the
      decompensated bladder, which would result in less inhibitory potency of CPI-17 on
      myosin light chain phosphatase activity and contribute to less contractility.
      Immunostaining revealed the colocalization of PKC and phosphorylated CPI-17 in
      the DSM and confirmed the decreases of these signaling proteins in the
      decompensated bladder. Our results show a differential PKC-mediated DSM
      contraction with corresponding alterations of PKC expression, activity and the
      phosphorylation of CPI-17. Our finding suggests a significant correlation between
      bladder function and PKC pathway. An impaired PKC pathway appears to be
      correlated with severe bladder dysfunction observed in decompensated bladders.

PMID- 19381132
TI  - Reactive oxygen species modulate growth of cerebral aneurysms: a study using the
      free radical scavenger edaravone and p47phox(-/-) mice.
AB  - Cerebral aneurysm (CA) is a relatively common disease and can cause a
      catastrophic subarachnoid hemorrhage with a high mortality and morbidity rate.
      Despite its clinical and social importance, the detailed mechanism of CA
      formation remains to be elucidated, resulting in the absence of effective medical
      treatment against CAs. Recent studies revealed that chronic inflammation in
      arterial walls by hemodynamic force is implicated in CA formation. Reactive
      oxygen species (ROS) are a major mediator of inflammation and actively
      participate in the pathogenesis of various vascular diseases. In the present
      study, we first assessed the expression of ROS-producing and -eliminating genes
      in CA walls by immunohistochemistry and RT-PCR analysis. The ROS-producing gene,
      p47phox, was upregulated in infiltrating macrophages and medial smooth muscle
      cells in arterial walls. Upregulated ROS-producing genes and suppressed ROS
      eliminating genes suggested that ROS overproduction occurred in aneurysmal walls.
      In situ superoxide imaging by dihydroethidium, which showed ROS overproduction in
      aneurysmal walls, confirmed this hypothesis. Edaravone, a powerful free radical
      scavenger, effectively inhibited CA formation by suppressing inflammation-related
      gene expression in aneurysmal walls. Furthermore, CA formation was markedly
      inhibited by p47phox deletion in mice and was accompanied by decreased
      inflammation in aneurysmal walls. These data suggested the active participation
      of ROS and p47phox in CA formation and the therapeutic potential of an ROS
      eliminating agent against CA formation.

PMID- 19381134
TI  - The final push?

PMID- 19381133
TI  - Interleukin-18 predicts atherosclerosis progression in SIV-infected and
      uninfected rhesus monkeys (Macaca mulatta) on a high-fat/high-cholesterol diet.
AB  - Interleukin (IL)-18 levels have been identified as important predictors of
      cardiovascular mortality and are often elevated in human immunodeficiency virus
      (HIV)-infected individuals. To investigate a possible function for IL-18 in
      atherogenesis in the context of early HIV infection, we used the simian
      immunodeficiency model of HIV infection. Acutely simian immunodeficiency virus
      infected and uninfected rhesus monkeys (Macaca mulatta) on an atherogenic diet
      were evaluated prospectively for atherosclerotic lesion development relative to a
      panel of plasma markers including IL-18, IL-8, IL-1beta, IL-6, C-reactive
      protein, soluble vascular cell adhesion molecule-1, soluble E-selectin, and
      soluble intercellular adhesion molecule-1. Although no significant differences in
      lesion development were identified between groups after 35 days of infection,
      levels of plasma IL-18 measured 1 month before virus inoculation correlated
      significantly with atherosclerotic plaque cross-sectional area at the carotid
      bifurcation (P<0.001, R=0.946), common iliac bifurcation (P<0.01, R=0.789), and
      cranial abdominal aorta (P<0.01, R=0.747), as well as with extent of CD3+ and
      CD68+ cellular infiltration in vascular lesions (both P<0.001, R>or=0.835) in
      both groups. Atherosclerotic plaque area at the carotid and common iliac
      bifurcations also showed a weaker inverse correlation with baseline IL-8 levels,
      as did CD68+ signal area. Results implicate a strong role for IL-18 in early
      atherosclerosis progression and raise the possibility that the chronically
      elevated IL-18 levels seen in later stages of HIV infection may contribute
      significantly to accelerated atherogenesis in this population.

PMID- 19381135
TI  - Aimez-vous Brahms? A story capriccioso from the discovery of a cytokine family
      and its regulators.

PMID- 19381136
TI  - Local advantage: skin DCs prime; skin memory T cells protect.

PMID- 19381137
TI  - Gaining entry to an uninflamed brain.

PMID- 19381138
TI  - Crohn's disease-associated Nod2 mutants reduce IL10 transcription.

PMID- 19381139
TI  - The Foxo and the hound: chasing the in vivo regulation of T cell populations
      during infection.

PMID- 19381145
TI  - Drug delivery in the twenty-first century: a new paradigm.

PMID- 19381141
TI  - Autophagy genes in immunity.
AB  - In its classical form, autophagy is a pathway by which cytoplasmic constituents,
      including intracellular pathogens, are sequestered in a double-membrane-bound
      autophagosome and delivered to the lysosome for degradation. This pathway has
      been linked to diverse aspects of innate and adaptive immunity, including
      pathogen resistance, production of type I interferon, antigen presentation,
      tolerance and lymphocyte development, as well as the negative regulation of
      cytokine signaling and inflammation. Most of these links have emerged from
      studies in which genes encoding molecules involved in autophagy are inactivated
      in immune effector cells. However, it is not yet known whether all of the
      critical functions of such genes in immunity represent 'classical autophagy' or
      possible as-yet-undefined autophagolysosome-independent functions of these genes.
      This review summarizes phenotypes that result from the inactivation of autophagy
      genes in the immune system and discusses the pleiotropic functions of autophagy
      genes in immunity.

PMID- 19381148
TI  - Studies should be controlled, randomized, and blinded.
AB  - Rigorous assessment of the efficacy and safety of a new therapy requires a
      concurrent control group, randomization, and blinding. The control group allows
      comparison with a contemporaneous patient group. Randomization, properly done,
      avoids systematic bias between treatment groups and should balance other factors,
      reducing the likelihood of group differences due to patient characteristics.
      Blinding minimizes the risk of biases stemming from patients' and assessors'
      beliefs, actions, and hopes about the treatment received. This is critical given
      the substantial effect that such beliefs can have on outcome, often termed the
      "placebo effect." New and exciting technologies would probably be particularly
      susceptible to the placebo effect, making blinding even more critical when
      studying such treatments.

PMID- 19381149
TI  - How well does blinding work in randomized controlled trials?: a counterpoint.

PMID- 19381150
TI  - Nanomedicine and society.
AB  - Nanomedicine is a reality of medical research and clinical practice, and it
      offers new and promising approaches to fundamental problems in medicine. Most
      prominent are the early detection of neoplastic disease and the individualized
      treatment of metastases. These potentially transformational developments require
      careful scrutiny of the potential impact of nanomedicine on society, so that the
      community can guide its deployment in keeping with the fundamental tenets of
      medical ethics.

PMID- 19381151
TI  - Combination products regulation at the FDA.
AB  - The US Food and Drug Administration (FDA) is responsible for protecting the
      public health by assuring the safety, efficacy, and security of drugs, biological
      products, and medical devices. As single-entity products, drugs are generally
      regulated by the Center for Drug Evaluation and Research (CDER), devices by the
      Center for Devices and Radiological Health (CDRH), and biologics by the Center
      for Biologics Evaluation and Research (CBER). In recent years, technological
      advances have led to a blurring of the historical lines of separation between the
      centers.

PMID- 19381154
TI  - Differences and similarities in the serotonergic diathesis for suicide attempts
      and mood disorders: a 22-year longitudinal gene-environment study.
AB  - To investigate similarities and differences in the serotonergic diathesis for
      mood disorders and suicide attempts, we conducted a study in a cohort followed
      longitudinally for 22 years. A total of 1255 members of this cohort, which is
      representative of the French-speaking population of Quebec, were investigated.
      Main outcome measures included (1) mood disorders (bipolar disorder and major
      depression) and suicide attempts by early adulthood; (2) odds ratios and
      probabilities associated with 143 single nucleotide polymorphisms in 11
      serotonergic genes, acting directly or as moderators in gene-environment
      interactions with childhood sexual or childhood physical abuse (CPA), and in gene
      gene interactions; (3) regression coefficients for putative endophenotypes for
      mood disorders (childhood anxiousness) and suicide attempts (childhood
      disruptiveness). Five genes showed significant adjusted effects (HTR2A, TPH1,
      HTR5A, SLC6A4 and HTR1A). Of these, HTR2A variation influenced both suicide
      attempts and mood disorders, although through different mechanisms. In suicide
      attempts, HTR2A variants (rs6561333, rs7997012 and rs1885884) were involved
      through interactions with histories of sexual and physical abuse whereas in mood
      disorders through one main effect (rs9316235). In terms of phenotype-specific
      contributions, TPH1 variation (rs10488683) was relevant only in the diathesis for
      suicide attempts. Three genes contributed exclusively to mood disorders, one
      through a main effect (HTR5A (rs1657268)) and two through gene-environment
      interactions with CPA (HTR1A (rs878567) and SLC6A4 (rs3794808)). Childhood
      anxiousness did not mediate the effects of HTR2A and HTR5A on mood disorders, nor
      did childhood disruptiveness mediate the effects of TPH1 on suicide attempts. Of
      the serotonergic genes implicated in mood disorders and suicidal behaviors, four
      exhibited phenotype-specific effects, suggesting that despite their high
      concordance and common genetic determinants, suicide attempts and mood disorders
      may also have partially independent etiological pathways. To identify where these
      pathways diverge, we need to understand the differential, phenotype-specific gene
      environment interactions such as the ones observed in the present study, using
      suitably powered samples.

PMID- 19381155
TI  - The effect of obesity combined with low muscle strength on decline in mobility in
      older persons: results from the InCHIANTI study.
AB  - OBJECTIVE: Both obesity and muscle impairment are increasingly prevalent among
      older persons and negatively affect health and physical functioning. However, the
      combined effect of coexisting obesity and muscle impairment on physical function
      decline has been little studied. We examined whether obese persons with low
      muscle strength experience significantly greater declines in walking speed and
      mobility than persons with only obesity or low muscle strength. DESIGN: Community
      dwelling adults aged > or = 65 years (n = 930) living in the Chianti geographic
      area (Tuscany, Italy) were followed for 6 years in the population-based InCHIANTI
      study. MEASUREMENTS: On the basis of baseline measurements (1998-2000), obesity
      was defined as body mass index (BMI) > or = 30 kg/m(2) and low muscle strength as
      lowest sex-specific tertile of knee extensor strength. Walking speed and self
      reported mobility disability (ability to walk 400 m or climb one flight of
      stairs) were assessed at baseline and at 3- and 6-year follow-up. RESULTS: At
      baseline, obese persons with low muscle strength had significantly lower walking
      speed compared with all other groups (P < or = 0.05). In longitudinal analyses,
      obese participants with low muscle strength had steeper decline in walking speed
      and high risk of developing new mobility disability over the 6-year follow-up
      compared with those without obesity or low muscle strength. After the age of 80,
      the differences between groups were substantially attenuated. The differences
      seen in walking speed across combination of low muscle strength and obesity
      groups were partly explained by 6-year changes in muscle strength, BMI and waist
      circumference. CONCLUSIONS: Obesity combined with low muscle strength increases
      the risk of decline in walking speed and developing mobility disability,
      especially among persons < 80 years old.

PMID- 19381156
TI  - Control of a neuroprosthesis for grasping using off-line classification of
      electrocorticographic signals: case study.
AB  - STUDY DESIGN: Proof of concept study to control a neuroprosthesis for grasping
      using identification of arm movements from ECoG signals. OBJECTIVE: To test the
      feasibility of using electrocorticographic (ECoG) signals as a control method for
      a neuroprosthesis for grasping. SETTING: Acute care hospital, Toronto Western
      Hospital and spinal cord injury (SCI) rehabilitation centre, Toronto
      Rehabilitation Institute, Lyndhurst Centre. Both hospitals are located in
      Toronto, Canada. METHODS: Two subjects participated in this study. The first
      subject had subdural electrodes implanted on the motor cortex for the treatment
      of essential tremor (ET). ECoG signals were recorded while the subject performed
      specific arm movements. The second subject had a complete SCI at C6 level (ASIA B
      score) and was fitted with a neuroprosthesis, capable of identifying arm
      movements from ECoG signals off-line, for grasping. To operate the
      neuroprosthesis, subject 2 issued a command that would trigger the release of a
      randomly selected ECoG signal recorded from subject 1, associated with a
      particular arm movement. The neuroprosthesis identified which arm movement was
      performed at the time of recording and used that information to trigger the
      stimulation sequence. A correct ECoG classification resulted in the
      neuroprosthesis producing the correct hand function (that is grasp and release).
      RESULTS: The neuroprosthesis classified ECoG signals correctly delivering the
      correct stimulation strategy with 94.5% accuracy. CONCLUSIONS: The feasibility of
      using ECoG signals as a control strategy for a neuroprosthesis for grasping was
      shown.

PMID- 19381158
TI  - Competing for help: new insights into the function of follicular helper T cells.

PMID- 19381157
TI  - Outcome measures in spinal cord injury: recent assessments and recommendations
      for future directions.
AB  - STUDY DESIGN: Review by the spinal cord outcomes partnership endeavor (SCOPE),
      which is a broad-based international consortium of scientists and clinical
      researchers representing academic institutions, industry, government agencies,
      not-for-profit organizations and foundations. OBJECTIVES: Assessment of current
      and evolving tools for evaluating human spinal cord injury (SCI) outcomes for
      both clinical diagnosis and clinical research studies. METHODS: a framework for
      the appraisal of evidence of metric properties was used to examine outcome tools
      or tests for accuracy, sensitivity, reliability and validity for human SCI.
      RESULTS: Imaging, neurological, functional, autonomic, sexual health,
      bladder/bowel, pain and psychosocial tools were evaluated. Several specific tools
      for human SCI studies have or are being developed to allow the more accurate
      determination for a clinically meaningful benefit (improvement in functional
      outcome or quality of life) being achieved as a result of a therapeutic
      intervention. CONCLUSION: Significant progress has been made, but further
      validation studies are required to identify the most appropriate tools for
      specific targets in a human SCI study or clinical trial.

PMID- 19381159
TI  - SOCS1 negatively regulates the production of Foxp3+ CD4+ T cells in the thymus.
AB  - SOCS1 profoundly influences the development and peripheral homeostasis of CD8+ T
      cells but has less impact on CD4+ T cells. Despite the moderate influence of
      SOCS1 in the development of the total CD4 T-cell lineage, we show here that SOCS1
      deficiency resulted in a 10-fold increase in Foxp3(+) CD4(+) T cells in the
      thymus. Increased numbers of Foxp3+ thymocytes occurred in mice with T-cell
      specific ablation of SOCS1, suggesting that the effect is T-cell intrinsic. This
      increase in Foxp3+ CD4+cells in SOCS1-deficient mice also occurred in the absence
      of IFN-gamma or/and IL-7 signaling. Increase in CD25+CD4+ T cells in the absence
      of SOCS1 could be partly due to enhanced survival by CD25+CD4+cells, to a lesser
      degree CD25-CD4+ T cells, from SOCS1-deficient mice with or without T-cell growth
      factors.

PMID- 19381160
TI  - Development of prophylactic and therapeutic vaccines using the ISCOMATRIX
      adjuvant.
AB  - Adjuvants are components that when added to subunit antigen (Ag) vaccines boost
      their immunogenicity and thus immune efficacy. However, there are few adjuvants
      that are approved for clinical use resulting in a critical need for the
      development of safe and effective adjuvants for use in both prophylactic and
      therapeutic vaccines. The paucity of appropriate adjuvants is more chronic for
      the development of therapeutic vaccines for cancer and chronic infectious
      disease, which need to induce cytotoxic T-cell responses via cross-presentation
      of the vaccine Ag by dendritic cells. The ISCOMATRIX adjuvant represents a unique
      adjuvant system that facilitates Ag delivery and presentation as well as
      immunomodulation to provide enhanced and accelerated immune responses. The immune
      responses generated are of broad specificity to the vaccine Ag, and include
      robust antibody responses of multiple subclasses as well as both CD4(+) and
      CD8(+) T-cell responses. Here we discuss our understanding of the mechanisms of
      action by which ISCOMATRIX adjuvant may facilitate these integrated immune
      responses and touch on insights gained through its clinical experience.

PMID- 19381161
TI  - A genetic polymorphism of matrix metalloproteinase 9 (MMP-9) affects the changes
      in circulating MMP-9 levels induced by highly active antiretroviral therapy in
      HIV patients.
AB  - We examined whether two functional polymorphisms (g.-1562C>T and g.-90(CA)14-24)
      in the matrix metalloproteinase (MMP)-9 gene or MMP-9 haplotypes affect the
      circulating levels of pro-MMP-9 and pro-MMP-9/TIMP-1 (tissue inhibitor of
      metalloproteinase-1) ratios in AIDS patients, and modulate alterations in these
      biomarkers after highly active antiretroviral therapy (HAART). We studied 82
      patients commencing HAART. Higher pro-MMP-9 concentrations and pro-MMP-9/TIMP-1
      ratios were found in CT/TT patients compared with CC patients. HAART decreased
      pro-MMP-9 levels and pro-MMP-9/TIMP-1 ratios in CT/TT patients, it did not modify
      pro-MMP-9 levels and it increased pro-MMP-9/TIMP-1 ratios in CC patients. The g.
      90(CA)14-24 polymorphism, however, produced no significant effects. Moreover, we
      found no significant differences in HAART-induced changes in plasma pro-MMP-9,
      TIMP-1 and pro-MMP-9/TIMP-1 ratios when different MMP-9 haplotypes were compared.
      These findings suggest that the g.-1562C>T polymorphism affects pro-MMP-9 levels
      in patients with AIDS and modulates the alterations in pro-MMP-9 levels caused by
      HAART, thus possibly affecting the risk of cardiovascular complications.

PMID- 19381162
TI  - Global variation in CYP2C8-CYP2C9 functional haplotypes.
AB  - We have studied the global frequency distributions of 10 single nucleotide
      polymorphisms (SNPs) across 132 kb of CYP2C8 and CYP2C9 in approximately 2500
      individuals representing 45 populations. Five of the SNPs were in noncoding
      sequences; the other five involved the more common missense variants (four in
      CYP2C8, one in CYP2C9) that change amino acids in the gene products. One
      haplotype containing two CYP2C8 coding variants and one CYP2C9 coding variant
      reaches an average frequency of 10% in Europe; a set of haplotypes with a
      different CYP2C8 coding variant reaches 17% in Africa. In both cases these
      haplotypes are found in other regions of the world at <1%. This considerable
      geographic variation in haplotype frequencies impacts the interpretation of
      CYP2C8/CYP2C9 association studies, and has pharmacogenomic implications for drug
      interactions.

PMID- 19381163
TI  - Pharmacogenetics and biomarkers in colorectal cancer.
AB  - The prognosis of patients with colorectal cancer (CRC) is affected by various
      factors at the time of diagnosis, including location of the tumor, gender, age
      and overall performance status of the patient. Predicting response and limiting
      drug-induced toxicity for patients with CRC are also critical. Interpatient
      differences in tumor response and drug toxicity are common during chemotherapy.
      Genomic variability of key metabolic enzyme complexes, drug targets and drug
      transport molecules are important contributing factors. At present, there is
      inconsistent and rather low use of pharmacogenetic testing in the clinical
      setting because of a lack of robust evidence or of resources. Patients' selection
      and tailored treatments by the introduction of genetic testing will hopefully
      allow better response prediction and limit drug-induced toxicity leading to
      improved patient outcomes in the most cost-effective way. Here, we review the
      main genetic alterations observed in familial and sporadic CRC and their
      associations with the metabolism, efficacy and toxicities of drugs used in this
      disease.

PMID- 19381164
TI  - Prevalence of CYP2C9 polymorphisms in the south of Europe.
AB  - CYP2C9 is a major liver enzyme responsible of the metabolism of many clinically
      important drugs. The presence of CYP2C9 genetic polymorphisms has been associated
      with marked interindividual variability in its catalytic activity that could
      result in drug toxicity. Here we present frequencies of the most common CYP2C9
      coding variants CYP2C9*2 (C430T) and CYP2C9*3 (A1075C) in representative samples
      of four regions from Spain (Basque Country, n=358; Catalonia, n=240; Central
      Spain, n=190 and Galicia, n=288) and one northern Italian region, (Verona,
      n=164), which range between 0.125 and 0.165 in the case of CYP2C9*2 and between
      0.071 and 0.085 for CYP2C9*3. No significant differences between CYP2C9 allele
      frequencies were found comparing all the sampled populations. A more extensive
      comparative analysis using allele frequency data of populations widely spread
      over Europe was performed, showing significant differences in the CYP2C9*2 allele
      frequencies distribution between some of the regions, being quite homogeneous in
      the case of CYP2C9*3 variant. The results obtained show that above 40% of our
      samples carry a mutate allele, which can result in a poor metabolization of low
      therapeutic index drugs as oral anticoagulants (warfarin, acenocoumarol), oral
      antidiabetic drugs and some non-steroidal anti-inflammatory drugs. Our study
      constitutes both a large (n=1240) and robust allele frequency database on CYP2C9
      polymorphisms, which represents one of the most numerous CYP2C9*2 and *3 database
      existing to date.

PMID- 19381165
TI  - Genetic variation in the organic cation transporter 1 is associated with
      metformin response in patients with diabetes mellitus.
AB  - The organic cation transporter 1, encoded by the SLC22A1 gene, is responsible for
      the uptake of the anti-hyperglycaemic drug, metformin, in the hepatocyte. We
      assessed whether a genetic variation in the SLC22A1 gene is associated with the
      glucose-lowering effect of metformin. Incident metformin users in the Rotterdam
      Study, whose HbA1c measurements were available, were identified. Associations
      between 11 tagging single nucleotide polymorphisms in the SLC22A1 gene and change
      in the HbA1c level were analyzed. A total of 102 incident metformin users were
      included in this study sample. Except for the rs622342 A>C polymorphism, no
      significant differences in metformin response were observed. For each minor C
      allele at rs622342, the reduction in HbA1c levels was 0.28% less (95% CI 0.09
      0.47, P=0.005). After Bonferroni correction, the P-value was 0.050. To conclude,
      genetic variation at rs622342 in the SLC22A1 gene was associated with the glucose
      lowering effect of metformin in patients with diabetes mellitus.

PMID- 19381166
TI  - Human herpesvirus miRNAs statistically preferentially target host genes involved
      in cell signaling and adhesion/junction pathways.

PMID- 19381167
TI  - The involvement of hypoxia-inducible factor 1 alpha in Toll-like receptor 7/8
      mediated inflammatory response.
AB  - Toll-like receptors (TLRs) 7 and 8 are crucial in host defence against single
      stranded RNA (ssRNA) viruses. Such viruses cause severe illnesses, which remain a
      serious medical burden in both industrialised and developing countries. TLR7/8
      downstream signaling leads to a dramatic cellular stress associated with energy
      consumption. However, the molecular mechanisms of cell survival and adaptation to
      TLR7/8-induced stress, which give the cells an opportunity to initiate proper
      inflammatory reactions, are not clear at all. Here we report for the first time
      that ligand-induced activation of TLR7/8 leads to the accumulation of hypoxia
      inducible factor 1 alpha (HIF-1alpha) protein in THP-1 human myeloid macrophages
      via redox- and reactive nitrogen species-dependent mechanisms. MAP kinases and
      phosphoinositol-3K are not involved in TLR7/8-mediated HIF-1alpha accumulation.
      Experiments with HIF-1alpha knockdown THP-1 cells have clearly demonstrated that
      HIF-1alpha is important for the protection of these cells against TLR7/8-induced
      depletion of ATP. Thus, HIF-1alpha might support both cell survival and the
      production of pro-inflammatory cytokines upon TLR7/8 activation.

PMID- 19381168
TI  - Simulation comparison of aircraft landing performance in foggy conditions aided
      by different UV sensors.
AB  - In the atmosphere pointlike sources are surrounded by an aureole due to molecular
      and aerosol scattering. UV phase functions of haze droplets have a very important
      forward peak that limits signal angular spreading in relation to the clear
      atmosphere case where Rayleigh scattering predominates. This specific property
      can be exploited using solar blind UV source detection as an aircraft landing aid
      under foggy conditions. Two methods have been used to compute UV light
      propagation, based on the Monte Carlo technique and a semi-empirical approach.
      Results obtained after addition of three types of sensor and UV runway light
      models show that an important improvement in landing conditions during foggy
      weather could be achieved by use of a solar blind UV intensified CCD camera with
      two stages of microchannel plates.

PMID- 19381169
TI  - Polarization dynamics in optical ground wire network.
AB  - We report the polarization dynamics in an optical ground wire (OPGW) network for
      a summer period and a fall period for what is believed to be the first time. To
      better observe the surrounding magnetic fields contribution to modulating the
      state of polarization (SOP) we installed a Faraday rotating mirror to correct
      reciprocal birefringence from quasi-static changes. We also monitored the OPGW
      while no electrical current was present in the towers' electrical conductors. The
      spectral analysis, the arc length mapped out over a given time interval on a
      Poincare sphere, histograms of the arc length, and the SOP autocorrelation
      function are calculated to analyze the SOP changes. Ambient temperature changes,
      wind, Sun-induced temperature gradients, and electrical current all have a
      significant impact on the SOP drift in an OPGW network. Wind-generated cable
      oscillations and Sun-induced temperature gradients are shown to be the dominant
      slow SOP modulations, while Aeolian vibrations and electrical current are shown
      to be the dominant fast SOP modulations. The spectral analysis revealed that the
      electrical current gives the fastest SOP modulation to be 300 Hz for the sampling
      frequency of 1 KHz. This has set the upper speed limit for real-time polarization
      mode dispersion compensation devices.

PMID- 19381170
TI  - Numerical model of an Er3+-Tm3+-Pr3+-codoped fiber amplifier pumped with an 800
      nm laser diode.
AB  - We present a numerical model of an Er3+-Tm3+-Pr3+ codoped fiber amplifier pumped
      with an 800 nm laser for the first time to the best of our knowledge. The rate
      and power propagation equations are solved numerically, and the dependence of the
      gains at 1310, 1470, and 1530 nm windows on the active ion concentrations and
      fiber length are calculated. The results show that with pump power of 20 mW, when
      Pr(3+)-Tm(3+)-Er(3+) concentrations are around 2.0 x 10(24), 2.0 x 10(24), and
      2.26 x 10(24) (ions/m3), respectively, the signals at 1310, 1470, and 1530 nm
      windows may be equally amplified in the active fiber with a length of 1.3 m.

PMID- 19381171
TI  - Laser induced damage of fused silica polished optics due to a droplet forming
      organic contaminant.
AB  - We report on the effect of organic molecular contamination on single shot laser
      induced damage density at the wavelength of 351 nm, with a 3 ns pulse length.
      Specific contamination experiments were made with dioctylphthalate (DOP) in
      liquid or gaseous phase, on the surface of fused silica polished samples, bare or
      solgel coated. Systematic laser induced damage was observed only in the case of
      liquid phase contamination. Different chemical and morphological characterization
      methods were used to identify and understand the damage process. We demonstrate
      that the contaminant morphology, rather than its physicochemical nature, can be
      responsible for the decrease of laser induced damage threshold of optics.

PMID- 19381172
TI  - Sagnac-interferometer-based characterization of spatial light modulators.
AB  - A method for characterizing the phase response of spatial light modulators (SLMs)
      by using a Sagnac interferometer is proposed and demonstrated. The method
      represents an improvement over conventional diffraction-based or interferometric
      techniques by providing a simple and accurate phase measurement while taking
      advantage of the inherent phase stability of a Sagnac interferometer. As a
      demonstration, the phase response of a commercial liquid crystal on a silicon SLM
      is characterized and then linearized by using a programmable lookup table. The
      transverse phase profile over the SLM surface is also measured.

PMID- 19381173
TI  - Pulse compression in an electro-optic Q-switched diode-pumped YVO4/Nd:YVO4 laser
      with a Cr4+:YAG saturable absorber.
AB  - A diode end-pumped doubly Q-switched YVO4/Nd:YVO4 laser has been realized for the
      first time to our knowledge by using both an electro-optic (EO) modulator and a
      Cr4):YAG saturable absorber. A 3.8 ns pulse width is generated by this laser
      under a pump power of 15 W at 2 kHz, which is obviously compressed in comparison
      with that of 8.8 ns from a single actively EO Q-switched laser. Under the same
      conditions, peak power values of 174.7 and 93 kW are also obtained. A coupled
      equation is given to theoretically analyze the experimental data. The
      experimental and theoretical results show that the doubly Q-switched laser has
      the advantages of a shorter pulse width and higher pulse peak power in contrast
      with a singly Q-switched laser.

PMID- 19381174
TI  - Long-period grating and its application in laser beam shaping in the 1.0 microm
      wavelength region.
AB  - Laser beam shaping is an important subject for industrial and medical
      applications since different applications may require different laser intensity
      distributions. We present an all-fiber beam-shaping device that could transform a
      Gaussian-shaped laser beam into an intensity uniform beam in the 1.0 microm
      wavelength region using a long-period grating (LPG). The device can be used to
      shape the beam of a Yb-doped high-power fiber laser. The mode structure of the
      LPGs made of HI1060 fiber is analyzed. The design parameters that affect the beam
      shaping are discussed, and the results of the beam shaping using two cladding
      modes, LP(03) and LP(04), are presented.

PMID- 19381175
TI  - Silver-doped photopolymer media for holographic recording.
AB  - Incorporation of silver ions into a dye-sensitized poly(vinyl alcohol)/acrylamide
      photopolymer is observed to give better performance compared to other metal-ion
      doped photopolymer holographic recording media. Plane-wave transmission gratings
      were recorded in the photopolymer films using a He-Ne laser, and various
      holographic parameters were optimized so as to explore maximum potential of the
      material for various holographic applications. Silver-doped films showed good
      energy sensitivity, and gratings recorded in optimized film exhibited a
      diffraction efficiency of more than 75%. The potential of the material for
      holographic data storage applications is also studied using peristrophic
      multiplexing.

PMID- 19381176
TI  - Sensing the hygroscopicity of polymer and copolymer materials using terahertz
      time-domain spectroscopy.
AB  - We present the hygroscopicity of polymer and copolymer materials in the low
      terahertz (THz) frequency range using a linear absorption model. We identify COC
      6013 and COC 5013 as optimal THz window materials, possessing both low
      hygroscopicity and high transmission in the THz regime. The correct choice of
      window material is of significance for transmission THz spectroscopy and of
      particular interest for THz liquid spectroscopy.

PMID- 19381177
TI  - Submicrosecond regular and chaotic nonlinear dynamics in a pulsed picosecond
      Nd:YAG laser with millisecond pumping.
AB  - We propose and study both numerically and experimentally a feedback-controlled
      laser system capable of generating regular bursts with a submicrosecond period.
      Bursting is obtained in a laser that is controlled by a combination of feedbacks
      in which the negative feedback loop action is delayed by one cavity round trip
      with respect to the positive one, and the period is adjusted by relative feedback
      sensitivity. The proper combination of feedbacks is realized in a Nd:YAG laser
      with millisecond pumping by means of a single optoelectronic negative feedback
      unit that utilizes the signal reflected from an intracavity Pockels cell
      polarizer. Regular bursting (microgroups of picosecond pulses) with controlled
      periods from 25 to 75 cavity round trips is obtained experimentally. The
      development of chaotic dynamics displayed by the system at a higher pumping level
      differs from the Feigenbaum scenario.

PMID- 19381178
TI  - Achromatic digital speckle pattern interferometer with constant radial in-plane
      sensitivity by using a diffractive optical element.
AB  - We report on a digital speckle pattern interferometer that applies a binary
      diffractive optical element (DOE) to generate double illumination and radial in
      plane sensitivity. The application of the DOE ensures independence on the
      wavelength of the laser used as an illumination source. Furthermore, in-plane
      sensitivity only depends on the grating period of the DOE. An experimental setup
      was built allowing the measurement of a set of radial in-plane displacement
      fields either using a red laser as a light source or a green one. When
      displacement fields computed from the measured optical phase maps obtained with a
      red or a green laser were compared, two main results were observed: (a)
      deviations between mean values ranged only up to 7 nm and (b) phase maps
      presented the same amount of fringes. In addition, phase maps measured with the
      red laser were processed as they were obtained with green light. For this case,
      deviations have ranged only up to 0.5 nm. On the other hand, a set of
      measurements performed changing the DOE by a conical mirror showed clearly that
      radial in-plane sensitivity increased when the red laser was changed by the green
      one.

PMID- 19381179
TI  - Design of microcavity organic light emitting diodes with optimized electrical and
      optical performance.
AB  - A multivariable and multiobjective organic light emitting diode (OLED) design and
      optimization procedure is presented that produces a microcavity OLED with optimal
      optical and electrical characteristics. We propose here a design procedure that
      splits the design process into two design stages where each stage can be
      optimized independently. In the first stage we design the OLED with optimal
      electrical and optical performance, where the mirrors are specified by their
      optimal spectral reflectivity, transmissivity, absorptance, and the phase shift
      on reflection. In the second stage we synthesize the top and the bottom
      multilayer mirrors with a minimal number of layers that satisfy the required
      optimal spectral dependencies determined in the first part of the design process.
      As a case study we present an optimized design for a top-emitting OLED with a
      simple bilayered cavity consisting of N, N'-di(naphthalene-1-yl)-N, N'
      diphenylbenzidine (NPB) as the hole transport layer and tris(8
      hydroxyquinoline)aluminium (Alq3) as the electron transport layer. Conventional
      devices with an ITO-LiF/Al electrode pair and a Ag?Ag electrode pair are used as
      reference devices to benchmark the performance of our design. Electrical
      simulations using the drift-diffusion model and optical simulations employing the
      integrated dipole antenna approach are implemented to test the performance of the
      devices. The optimized device shows improved optical and electrical performance
      when compared with the reference devices.

PMID- 19381180
TI  - Atmospheric occultation of optical intersatellite links: coherence loss and
      related parameters.
AB  - The Rytov theory is applied to find the wave structure function of a laser beam
      transmitted from one satellite to another and propagating through the turbulent
      atmosphere. The phase-screen approximation is used. Taking into account
      refractive-index anisotropy, outer scale, and atmospheric mean-refraction
      defocusing, we provide expressions of the wave structure function for a spherical
      wave. The width and time of coherence at the receiver are evaluated. Expression
      for the beam spread is found using the extended Huygens-Fresnel principle, and
      beam wander is assessed. Beam wander occurs only for very narrow beams. Links
      involving low-Earth-orbit and geosynchronous satellites are studied as examples.
      Finally, conditions where optical tracking is perturbed by the atmosphere are
      examined.

PMID- 19381181
TI  - Temperature and strain discrimination based on a temperature-insensitive
      birefringent interferometer incorporating an erbium-doped fiber.
AB  - A simple configuration for simultaneous measurement of temperature and strain
      exploiting a temperature-insensitive birefringent interferometer based on a
      photonic crystal fiber incorporating an erbium-doped fiber (EDF) is investigated.
      The transmission peak power of the birefringent interferometer incorporating the
      EDF is changed by the temperature variation because the amplified spontaneous
      emission of the EDF strongly depends on temperature. The applied strain changes
      the peak wavelength of the birefringent interferometer connecting with the EDF,
      which can make it possible to discriminate concurrent sensitivities like
      temperature and strain. The temperature and strain sensitivities were -0.04 dB/
      degrees C and 1.3 pm/microepsilon, respectively.

PMID- 19381182
TI  - Optofluidic variable focus lenses.
AB  - Here we propose optofluidic spherical microlenses that can change their focal
      distance by varying the refractive index of the liquid that composes them. These
      lenses are fabricated in the bulk of a polymeric mixture. Results of a
      characterization study of the profile of the lenses, the image forming
      capability, and the behavior of the focal distance as a function of the
      refractive index are presented. Ionic liquids are suggested as a source of
      liquids useful for fabricating this type of lens.

PMID- 19381183
TI  - Indirect broadband optical monitoring with multiple witness substrates.
AB  - We present an indirect broadband optical monitoring approach based on using
      several witness substrates that are brought to a measurement position in a
      special sequence. Different witness substrates are used to monitor not groups of
      successive design layers but specially chosen design layers. An attractive
      feature of the presented monitoring approach is the ability to reliably control
      thin dielectric and metal layers. Considered examples demonstrate a good accuracy
      of the proposed approach.

PMID- 19381184
TI  - Performance evaluation of a dual fringe-imaging Michelson interferometer for air
      parameter measurements with a 355 nm Rayleigh-Mie lidar.
AB  - A new concept of spectrum analyzer is proposed for short-range lidar measurements
      in airborne applications. It implements a combination of two fringe-imaging
      Michelson interferometers to analyze the Rayleigh-Mie spectrum backscattered by
      molecules and particles at 355 nm. The objective is to perform simultaneous
      measurements of four variables: the air speed, the air temperature and density,
      and the particle scattering ratio. The Cramer-Rao bounds are calculated to
      evaluate the best expectable measurement accuracies. The performance optimization
      shows that a Michelson interferometer with a path difference of 3 cm is optimal
      for air speed measurements in clear air. To optimize density, temperature, and
      scattering ratio measurements, the second interferometer should be set to a path
      difference of 10 cm at least; 20 cm would be better to be less sensitive to the
      actual Rayleigh-Brillouin line shape.

PMID- 19381185
TI  - Principle and analysis of a polarization imaging spectrometer.
AB  - A polarization imaging spectrometer based on a modified Savart polariscope with a
      moving wedge prism is presented. The principle of the instrument is described,
      and the optical path difference as a function of the moving wedge prism's moving
      displacement is calculated and analyzed. It employs a common-path configuration
      and is not sensitive to the nonuniform variation of moving speed and
      environmental vibrations. In comparison with the polarization imaging
      spectrometer based on the Savart polariscope, this spectrometer is a framing
      instrument rather than a pushbrooming device. Only the transmission of
      birefringent materials and detector sensitivity limit the available spectral
      range of such an instrument.

PMID- 19381186
TI  - Opto-optical gain-clamped L-band erbium-doped fiber amplifier with C-band control
      signal.
AB  - We demonstrate an opto-optical gain-clamped L-band erbium-doped fiber amplifier
      by manipulating the C-band lasing wavelength as the control signal. The L-band
      gain-clamped value is achieved by tuning the control laser in the C-band
      wavelength range that propagates in the opposite direction to the L-band signal.
      Within the wavelength range of 1538 nm and 1560 nm, the L-band gain decreases
      linearly with the increment of the C-band lasing wavelength. The L-band gain
      dynamic range decreases with the increment of the cavity loss. By combining two
      different levels of cavity loss, the gain dynamic range of 10 dB from 11 dB to 21
      dB is achieved with an average noise figure of less than 5.9 dB. The whole gain
      spectrum of the L-band can be used for multiple-channel amplification because the
      laser is created outside its signal band.

PMID- 19381187
TI  - Precise wavelength calibration in continuous-wave cavity ringdown spectroscopy
      based on the HITRAN database.
AB  - We describe the wavelength calibration method of a narrowband laser diode in
      continuous-wave (CW) cavity ringdown spectroscopy (CRDS). The method uses known
      spectral lines as wavelength markers to calibrate and refine the wavelength
      current relation of laser diodes, and their spectral positions are taken directly
      from the HITRAN 2004 database. We built a compact CW CRDS apparatus with a 1.517
      microm (approximately 6594 cm-1) distributed feedback (DFB) laser diode as the
      light source and a 25 cm long glass ceramic as the cavity in which to demonstrate
      the method. A wavelength precision of approximately 0.8 x 10(-3) cm-1 was
      obtained by comparing the HITRAN 2004 database, which was approximately four
      times more precise than that of the conventional method.

PMID- 19381188
TI  - Blind deconvolution of a noisy degraded image.
AB  - We develop a unified algorithm for performing blind deconvolution of a noisy
      degraded image. By incorporating a low-pass filter into the asymmetric
      multiplicative iterative algorithm and extending it to multiframe blind
      deconvolution, this algorithm accomplishes the blind deconvolution and noise
      removal concurrently. We report numerical experiments of applying the algorithm
      to the restoration of short-exposure atmosphere turbulence degraded images. These
      experiments evidently demonstrate that the unified algorithm has both good blind
      deconvolution performance and high-resolution image restoration.

PMID- 19381189
TI  - Impulse attack-free four random phase mask encryption based on a 4-f optical
      system.
AB  - Optical encryption methods based on double random phase encryption (DRPE) have
      been shown to be vulnerable to different types of attacks. The Fourier plane
      random phase mask (RPM), which is the most important key, can be cracked with a
      single impulse function attack. Such an attack is viable because the Fourier
      transform of a delta function is a unity function. Formation of a unity function
      can be avoided if RPMs are placed in front of both lenses in a 4-f optical setup,
      thereby protecting the DRPE from an impulse attack. We have performed numerical
      simulations to verify the proposed scheme. Resistance of this scheme is checked
      against the brute force and the impulse function attacks. The experimental
      results validate the feasibility of the scheme.

PMID- 19381190
TI  - Scene-based nonuniformity correction technique for infrared focal-plane arrays.
AB  - A scene-based nonuniformity correction algorithm is presented to compensate for
      the gain and bias nonuniformity in infrared focal-plane array sensors, which can
      be separated into three parts. First, an interframe-prediction method is used to
      estimate the true scene, since nonuniformity correction is a typical blind
      estimation problem and both scene values and detector parameters are unavailable.
      Second, the estimated scene, along with its corresponding observed data obtained
      by detectors, is employed to update the gain and the bias by means of a line
      fitting technique. Finally, with these nonuniformity parameters, the compensated
      output of each detector is obtained by computing a very simple formula. The
      advantages of the proposed algorithm lie in its low computational complexity and
      storage requirements and ability to capture temporal drifts in the nonuniformity
      parameters. The performance of every module is demonstrated with simulated and
      real infrared image sequences. Experimental results indicate that the proposed
      algorithm exhibits a superior correction effect.

PMID- 19381191
TI  - Development of a temporal filtering technique for suppression of interferences in
      applied laser-induced fluorescence diagnostics.
AB  - A temporal filtering technique, complementary to spectral filtering, has been
      developed for laser-induced fluorescence measurements. The filter is applicable
      in cases where the laser-induced interfering signals and the signal of interest
      have different temporal characteristics. For the interfering-signal
      discrimination a picosecond laser system along with a fast time-gated intensified
      CCD camera were used. In order to demonstrate and evaluate the temporal filtering
      concept two measurement situations were investigated; one where toluene
      fluorescence was discriminated from interfering luminescence of an aluminum
      surface, and in the other one Mie scattering signals from a water aerosol were
      filtered out from acetone fluorescence images. A mathematical model was developed
      to simulate and evaluate the temporal filter for a general measurement situation
      based on pulsed-laser excitation together with time-gated detection. Using system
      parameters measured with a streak camera, the model was validated for LIF imaging
      of acetone vapor inside a water aerosol. The results show that the temporal
      filter is capable of efficient suppression of interfering signal contributions.
      The photophysical properties of several species commonly studied by LIF in
      combustion research have been listed and discussed to provide guidelines for
      optimum use of the technique.

PMID- 19381192
TI  - Analysis of long-term measurements of laser propagation over the Chesapeake Bay.
AB  - Parameters characterizing the atmospheric turbulence in a 16 km maritime optical
      link were measured for the months of January through June of 2007 on a continuous
      basis, as conditions allowed. Both the scintillation index sigmaI(2) and the
      atmospheric structure constant Cn(2) are found to have a strong dependence on the
      air-minus-water temperature difference. There is no obvious diurnal variation of
      Cn(2) or of sigmaI(2) akin to the reduction in turbulence level seen in
      terrestrial links in the hour before sunrise and the hour after sunset. Results
      from the analysis of these data highlight a need for new approaches to modeling
      beam propagation in a maritime environment.

PMID- 19381193
TI  - Steerable spatial phase shifting applied to single-image closed-fringe
      interferograms.
AB  - It is well known that spatial phase shifting interferometry (SPSI) may be used to
      demodulate two-dimensional (2D) spatial-carrier interferograms. In these cases
      the application of SPSI is straightforward because the modulating phase is a
      monotonic increasing function of space. However, this is not true when we apply
      SPSI to demodulate a single-image interferogram containing closed fringes. This
      is because using these algorithms, one would obtain a wrongly demodulated
      monotonic phase all over the 2D space. We present a technique to overcome this
      drawback and to allow any SPSI algorithm to be used as a single-image fringe
      pattern demodulator containing closed fringes. We make use of the 2D spatial
      orientation direction of the fringes to steer (orient) the one-dimensional SPSI
      algorithm in order to correctly demodulate the nonmonotonic 2D phase all over the
      interferogram.

PMID- 19381194
TI  - Introduction.
AB  - The past few years have seen remarkable developments in the ability to control
      atomic motion by optical techniques. Among the key tools that have been developed
      for this purpose are the techniques of laser cooling, the significance of which
      was recognized by the award of the 1997 Nobel Prize in Physics to Steven Chu,
      Claude Cohen-Tannoudji, and William Phillips. These techniques have made it
      possible to cool atoms to temperatures lower than have been produced in any other
      physical system - around 10(-8) degrees Kelvin above absolute zero - and to
      confine those in traps for extended periods of observation.

PMID- 19381195
TI  - Experimental studies of Bose-Einstein condensation.
AB  - We describe several experimental studies of Bose-Einstein condensation in a
      dilute gas of sodium atoms. These include studies of static and dynamic behavior
      of the condensate, and of its coherence properties.

PMID- 19381196
TI  - Doppler imaging of plasma modes in a Penning trap.
AB  - We describe a technique and present results for imaging the modes of a laser
      cooled plasma of 9 Be + ions in a Penning trap. The modes are excited by
      sinusoidally time-varying potentials applied to the trap electrodes. They are
      imaged by changes in the ion resonance fluorescence produced by Doppler shifts
      from the coherent ion velocities of the mode. For the geometry and conditions of
      this experiment, the mode frequencies and eigenfunctions have been calculated
      analytically. A comparison between theory and experiment for some of the
      azimuthally symmetric modes shows good agreement.

PMID- 19381197
TI  - Strong evaporative cooling of a trapped cesium gas.
AB  - Using forced radio-frequency evaporation, we have cooled cesium atoms prepared in
      the sublevel F = -m(F) = 3 and confined in a magnetic trap. At the end of the
      evaporation ramp, the sample contains ~ 7000 atoms at 80 nK, corresponding to a
      phase space density 3 x 10(-2). A molecular dynamics approach, including the
      effect of gravity, gives a good account for the experimental data, assuming a
      scattering length larger than 300 Angstrom.

PMID- 19381198
TI  - Studies of two-species Bose-Einstein condesation.
AB  - We describe our recent progress on the investigation of two-species Bose-Einstein
      condensation. From a theoretical analysis we show that there is a new rich
      phenomenology associated with two-species Bose-Einstein condensates which does
      not exist in a single-species condensate. We then describe results of a numerical
      model of the evaporative cooling process of a trapped two-species gas.

PMID- 19381199
TI  - Introduction.
AB  - Decoherence and decay of quantum states in open systems is the main obstacle
      towards the realization of quantum computing and communications and a major
      impediment for coherent control (of atomic, molecular and condensed-phase
      processes) and quantum state engineering (of fields and atoms in cavities and
      trapped ions). This Focus Issue is an attempt to highlight the development of
      schemes for the control of quantum decay and decoherence, by presenting the major
      trends in this area. To this end, I have solicited a number of articles from
      groups that have been particularly active in the pursuit of these trends.

PMID- 19381200
TI  - Quantum control by compensation of quantum fluctuations.
AB  - We show that the influence of quantum fluctuations in the electromagnetic field
      vacuum on a two level atom can be measured and consequently compensated by
      balanced homodyne detection and a coherent feedback field. This compensation
      suppresses the decoherence associated with spontaneous emissions for a specific
      state of the atomic system allowing complete control of the coherent state of the
      system.

PMID- 19381201
TI  - Multimode unravelling of master equation and decoherence problem.
AB  - An unravelling of master equation for a set of fields interfering with one
      another is developed and conditions are found under which decoherence can be
      avoided for conditional and unconditional evolution of one of these fields.

PMID- 19381202
TI  - Control of non-Markovian decay and decoherence by measurements and interference.
AB  - Novel methods are discussed for the state control of atoms coupled to multi-mode
      reservoirs with non-Markovian spectra: 1) Excitation decay control : we point out
      that the quantum Zeno effect, i.e., inhibition of spontaneous decay by frequent
      measurements, is observable in open cavities and waveguides using a sequence of
      evolution- interrupting pulses or randomly-modulated CW fields. 2) Location
      dependent interference of decay channels - nonadiabatic (resonant) control : We
      show that the control of populations and coherences of two metastable states is
      feasible via resonant single-photon absorption to an intermediate state, by
      controlled spontaneous emission in a cavity. 3) Decoherence control by
      conditionally interfering parallel evolutions: We demonstrate that an arbitrary
      internal atomic state can be completely protected from decoherence by
      interference of its interactions with the reservoir over many different time
      interals in parallel . Such interference is conditional upon the detection of
      appropriate atomic-momentum observables. Realization in cavities is suggested.
      The rich arsenal of control methods described above can improve the performance
      of single-atom devices. It can also advance the state-of-the-art of quantum
      information encoding and processing.

PMID- 19381203
TI  - Synthesis of arbitrary superposition of Zeeman states in an atom.
AB  - We present a general strategy of quantum state engineering. We describe how an
      arbitarily prescribed superposition of internal Zeeman levels of an atom can be
      prepared by Raman pulses.

PMID- 19381204
TI  - Characterization of decoherence processes in quantum computation.
AB  - We show how the dynamics of open quantum systems can be fully characterized by
      using quantum tomography methods. We apply these methods to the case of an ion
      trap quantum computer, which does not operate under ideal conditions due to
      coupling to several environments. We study the performance of a fundamental two-
      bit quantum gate as a function of various parameters related to the interaction
      of the ions with external laser fields.

PMID- 19381205
TI  - Weisskopf-Wigner decay of excited oscillator states.
AB  - We investigate the analogy between exponential decay of a quantum system into a
      continuum, and laser-induced excitation of a molecular wave packet. We find that
      the analogy exists, but it is not as clear-cut for the excited vibrational states
      of the electronic molecular ground state, as it is for the corresponding
      vibrational ground state.

PMID- 19381206
TI  - Optical Monte Carlo modeling of a true portwine stain anatomy.
AB  - A unique Monte Carlo program capable of accommodating an arbitrarily complex
      geometry was used to determine the energy deposition in a true port wine stain
      anatomy. Serial histologic sections taken from a biopsy of a dark red, laser
      therapy resistant stain were digitized and used to create the program input for
      simulation at wavelengths of 532 and 585 nm. At both wavelengths, the greatest
      energy deposition occurred in the superficial blood vessels, and subsequently
      decreased with depth as the laser beam was attenuated. However, more energy was
      deposited in the epidermis and superficial blood vessels at 532 nm than at 585
      nm.

PMID- 19381207
TI  - Circular anisotropy of a rotating Fabry-Perot cavity.
AB  - A theoretical investigation was done concerning the resonant properties of a
      rotating Fabry-Perot cavity with dielectric media inside. The frequency splitting
      of orthogonal circularly-polarized modes had been predicted. Formula for the
      frequency splitting was obtained taking into account refractive index dispersion,
      dynamic-optical effect and the transversal structure of the electromagnetic
      field. We represent a simplified analysis, based on the geometrical optical
      theory, and we also present an accurate analysis on the basis of the general
      theory of relativity.

PMID- 19381208
TI  - Non-stationary scattering of wave-packets.
AB  - Potential scattering of free-electron wave packets is considered in the framework
      of non-stationary quantum-mechanical theory. The general expression for the
      average angle of scattering is obtained. The traditional quantum-mechanical plane
      wave approximation and classical results are shown to be incorporated in the
      results derived.

PMID- 19381209
TI  - A novel method for fast imaging of brain function, non-invasively, with light.
AB  - Imaging of the human body by any non-invasive technique has been an appropriate
      goal of physics and medicine, and great success has been obtained with both
      Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) in brain
      imaging. Non-imaging responses to functional activation using near infrared
      spectroscopy of brain (fNIR) obtained in 1993 (Chance, et al. [1]) and in 1994
      (Tamura, et al. [2]) are now complemented with images of pre-frontal and parietal
      stimulation in adults and pre-term neonates in this communication (see also [3]).
      Prior studies used continuous [4], pulsed [3] or modulated [5] light. The
      amplitude and phase cancellation of optical patterns as demonstrated for single
      source detector pairs affords remarkable sensitivity of small object detection in
      model systems [6]. The methods have now been elaborated with multiple source
      detector combinations (nine sources, four detectors). Using simple back
      projection algorithms it is now possible to image sensorimotor and cognitive
      activation of adult and pre- and full-term neonate human brain function in times
      < 30 sec and with two dimensional resolutions of < 1 cm in two dimensional
      displays. The method can be used in evaluation of adult and neonatal cerebral
      dysfunction in a simple, portable and affordable method that does not require
      immobilization, as contrasted to MRI and PET.

PMID- 19381210
TI  - Spatio-spectral dynamics and spontaneous ultrafast optical switching in VCSEL
      arrays.
AB  - Microscopic simulations on the basis of semiconductor Maxwell-Bloch equations
      show that in the short-time spatio-temporal dynamics of large aspect vertical
      cavity surface emitting lasers (VCSEL) and coupled VCSEL-arrays microscopic and
      macroscopic effects are intrinsically coupled. The combination of microscopic
      spatial and spectral dynamics of the carrier distribution functions and the
      nonlinear polarization of the active semiconductor medium reveal spatio-spectral
      hole-burning effects as the origin of ultra-fast mode-switching effects. In
      coupled VCSEL-arrays the simulations predict the emergence of spontaneous ultra
      fast spatial switching.

PMID- 19381211
TI  - Introduction.
AB  - This issue of Optics Express deals with multiple quantum well optically addressed
      spatial light modulators (MQW-OASLM) . These devices were first demonstrated at
      Bell labs in Alistair Glass' group by Dave Nolte and Afshin Partovi.

PMID- 19381212
TI  - Transient dynamics during two-wave mixing in photorefractive quantum well diodes
      using moving gratings.
AB  - The temporal dynamics of photorefractive and absorptive gains during two-wave
      mixing in Stark geometry photorefractive quantum wells are investigated using
      moving gratings to break the symmetry of the photorefractive diodes to achieve
      nonreciprocal energy transfer between two coherent laser beams.

PMID- 19381213
TI  - Direct-to-video holographic 3-D imaging using photorefractive multiple quantum
      well devices.
AB  - Customised photorefractive quantum well devices have been developed for real-time
      video acquisition of coherence-gated, three-dimensional images. Holographic
      imaging with direct video capture has been demonstrated. The technique has been
      applied to 3-D imaging through turbid media with 50 mm transverse and 60 mm depth
      resolution being achieved using near infrared light through a phantom of 13 mean
      free paths scattering depth. Spectrally-resolved holographic imaging has also
      been demonstrated.

PMID- 19381214
TI  - Speckle photography using optically addressed multiple quantum well spatial light
      modulators.
AB  - We demonstrate speckle photography using an optically addressed multiple quantum
      well spatial light modulator. An optical Fourier transform is used to allow real
      time displacement measurements.

PMID- 19381215
TI  - Introduction.
AB  - Nonlinear and guided wave optics and photorefractive effects are matured
      sciences, and are playing an ever increasing role in various fundamental and
      applied research fields. In the spirit of the focused issues, we have
      deliberately narrowed our attention to novel, unusual but no less interesting
      areas of pursuits. Although this focus issue contains only six papers, the
      readers will notice that it covers quite a range of material systems and optical
      processes. The so-called guiding core materials include semiconductors, crystals,
      liquid crystals and liquids; understandably, gaseous cores are not included at
      this point in time. The nonlinear optical effects arise from quantum processes in
      semiconductors, electron-holes in photorefractive crystals and multi-photon and
      excited electronic-state absorptions in molecules, as well as from truly
      classical processes such as elastic torques and hydrodynamics in liquid crystals,
      and thermal and density fluctuations in liquids.

PMID- 19381216
TI  - Soliton-emitting AlGaAs waveguide.
AB  - Simulations of soliton emission and propagation in a linear AlGaAs waveguide with
      one nonlinear cladding are presented. The device, which has realistic parameters,
      operates below half the bandgap and emits light into the cladding for a given
      input power. The use of selective disordering of the MQW guiding layer to realize
      the linear/nonlinear sections is discussed.

PMID- 19381217
TI  - Surface emitted second-harmonic generation from a quasi-phase matched waveguide
      in an Al(x)Ga(1-x)As/Al(2)O(3) microcavity.
AB  - A nonlinear Al(x)Ga(1-x)As waveguide consisting of a quasi-phase matched
      heterostructure embedded in a microcavity has been designed and fabricated. The
      microcavity resonator is formed by Al(2)O(3)/Al(0.32)Ga(0.68)As multilayer
      mirrors located above and below the waveguide core. The cavity resonantly
      enhances the surface emitting second-harmonic generation. The SH conversion
      efficiency has been measured for wavelengths between l = 1525 and 1575 nm. A
      simple waveguide loss measurement technique based on the SH autocorrelation of
      short optical pulses in a III-V waveguide is also demonstrated.

PMID- 19381218
TI  - Nolinear optical liquid cored fiber array and liquid crystal film fo ps-cw
      frequency agile laser optical limiting application.
AB  - The molecular nonlinear photonic absorption processes of two nonlinear fiber core
      liquids are discussed in the context of nonlinear propagation and optical
      limiting of short pulses. These fiber arrays are capable of limiting threshold
      and clamped output below 1 micro J for picosecond and nanosecond pulses. We also
      discuss the observation of perhaps the largest optical nonlinearity in some dye
      doped nematic liquid crystal films. These films will provide limiting action with
      a threshold power of 100 nWatt and limited transmission of << 1 microJoule for ms
      - cw laser.

PMID- 19381219
TI  - Non linearly induced self waveguiding structure in dye doped nematic liquid
      crystals confined in capillaries.
AB  - We report on experiments dealing with the propagation of a collimated laser beam
      in a dye doped nematic confined in a capillary of optical fiber size. The nematic
      is aligned in a such a way that the source beam is self focused. The behavior of
      the beam - focusing, multifocus regime, filamentation and undulation - already
      observed in larger cylindrical geometry and pure nematic is shown here to be
      reproduced in the dye doped medium, at much lower powers. Another feature is
      reported here: a stable regime looking like a waveguide appears in certain
      conditions, in which the beam to propagate in a narrow tube. This regime is
      simply modeled in terms of saturated reorientation of the nematic.

PMID- 19381220
TI  - Holographic recording in specially doped lithium niobate crystals.
AB  - A set of twelve specially doped lithium niobate crystals were grown to test the
      effect of the dopant on holographic recording in the crystals via the
      photorefractive effect. The crystals were doped with Ce, Co, Cr, Cu, Fe, Mn, Ni,
      Rh, Tb, Fe:Ce, Fe:Cr, and Fe:Mn. The transmission spectra was measured for each
      crystal and holograms have been written in each of the crystals with wavelengths
      from 457 nm to 671 nm. The wavelength sensitivity, scattering, and stability of
      the holograms varied substantially among the crystals. A qualitative description
      of the hologram's properties and a comparison of sensitivities between the
      crystals will be presented.

PMID- 19381221
TI  - Fabricating micro-Bragg reflectors in 3-D photorefractive waveguides.
AB  - Bragg reflectors as small as optical waveguides can be used at the intersections
      of waveguides as spectral filters, beam splitters, or beam combiners. We present
      the concept of fabricating small Bragg reflectors in photorefractive waveguides
      and show the spectral selectivity of these micro-Bragg reflectors fabricated in a
      lithium niobate crystal. We also show that we can fabricate waveguide structures
      simultaneously with the micro-Bragg reflector, by using a crystal whose c-axis is
      directed 45 degree off the optical axis of the fabrication beam. The reflectivity
      of the micro-Bragg reflector was smaller than 0.01 and was not large enough for
      the immediate use.

PMID- 19381222
TI  - Enhanced diffiraction limited output powerof tapered gain semiconductor lasers.
AB  - The spatiotemporal dynamics of linearly and trumpet flared high brightness
      semiconductor lasers are compared and contrasted using a comprehensive model
      built up from the microscopic physics. While both devices display complex multi
      longitudinal mode dynamics, the trumpet flared device is less susceptible to
      transverse filamentation instabilities and, hence, displays superior time
      averaged far-field imaging properties.

PMID- 19381223
TI  - Introduction.
AB  - Finding defects in materials using optics has a long and glorious history. The
      very first optical detection method used by humans was, of course, based on
      simple visual inspection. After the invention of the microscope (possibly the
      greatest optical invention ever), material inspection techniques took a great
      leap forward. In recent decades, with the invention of the laser and other
      advances in science and technology, there have been dramatic improvements in
      existing optical inspection techniques and the creation of many new ones. In this
      issue, we have collected four papers from different areas of optics that
      highlight important advances that have been made in material inspection
      techniques.

PMID- 19381224
TI  - Optical interferometric technique for deformation analysis.
AB  - We have developed a unique optical interferometric technique for deformation
      analysis and have applied it to tensile analyses of aluminum based samples. Using
      a recent theory of plastic deformation, this technique is capable of diagnosing
      whether the sample is close to a fracture and where the fracture will occur. It
      is also capable of diagnosing the current degree of stress concentration being
      developed in the sample. The theoretical basis of this method and some
      experimental results are presented.

PMID- 19381225
TI  - Improved resolution and signal-to-noise ratio in laser-ultrasonics by SAFT
      processing.
AB  - Laser-ultrasonics is an emerging nondestructive technique using lasers for the
      generation and detection of ultrasound which presents numerous advantages for
      industrial inspection. In this paper, the problem of detection by laser
      ultrasonics of small defects within a material is addressed. Experimental results
      obtained with laser-ultrasonics are processed using the Synthetic Aperture
      Focusing Technique (SAFT), yielding improved flaw detectability and spatial
      resolution. Experiments have been performed on an aluminum sample with a
      contoured back surface and two flat-bottom holes. Practical interest of coupling
      SAFT to laser-ultrasonics is also discussed.

PMID- 19381226
TI  - Subsurface defect detection in materials using optical coherence tomography.
AB  - We have used optical coherence tomography to study the internal structure of a
      variety of non-biological materials. In particular, we have imaged internal
      regions from a commercial grade of lead zirconate titanate ceramic material, from
      a sample of single-crystal silicon carbide, and from a Teflon-coated wire. In
      each case the spatial positions of internal defects were determined.

PMID- 19381227
TI  - A high resolution, holographically corrected microscope with a Fresnel lens
      objective at large working distances.
AB  - We present details of a microscope which incorporates an inexpensive, high
      numerical aperture Fresnel lens objective. The system aberrations are corrected
      by the use of an image hologram of the lens recorded using a point source of
      coherent illumination. This device gives high resolution, real time imaging while
      maintaining a large working distance. The same microscope can be used for
      micromachining and photolithography in situations where close proximity to the
      sample is impossible or undesirable.

PMID- 19381228
TI  - Direct-to-video holographic 3-D imaging using photorefractive multiple quantum
      well devices: errata.
AB  - Due to an oversight during the revision process, one of the authors was not
      mentioned in this paper. The author list should read: R. Jones, M. Tziraki, D.
      Parsons Karavassilis, P. M. W. French, K. M. Kwolek, D. D. Nolte and M. R.
      Melloch.

PMID- 19381229
TI  - Editorial.
AB  - It's hard to believe, but a full year has passed since OSA launched Optics
      Express. From the start, we had several aims: 1). to be recognized as a peer
      reviewed optics journal at the level of quality associated with the OSA, 2). to
      publish the best in optics science and technology with minimal delay to authors,
      3). to provide convenient means through the Web for publishing material with
      video and audio-video and other multimedia components, and 4). to allow a world
      wide readership immediate access to the results of new research in optics. Now we
      can give an assessment of where we are, and say where we plan to go in the
      future.

PMID- 19381230
TI  - Introduction.
AB  - Photonic band structures or photonic crystals are periodic dielectric structures
      that have variations in two or three dimensions but also include the familiar one
      dimensional layered dielectric structures. Photonic crystals are developing
      potential technological solutions to some perplexing problems in optoelectronics,
      and in microwave or RF detection. The complex nature of the field dynamics in
      these structures necessitates the development of numerically intensive
      computations that can provide answers to design problems.

PMID- 19381231
TI  - Channel drop filters in photonic crystals.
AB  - We present a general analysis of channel drop filter structures composed of two
      waveguides and an optical resonator system. We show that 100% transfer between
      the two waveguides can occur by creating resonant states of different symmetry,
      and by forcing an accidental degeneracy between them. The degeneracy must exist
      in both the real and imaginary parts of the frequency. Based on the analysis we
      present novel photonic crystal channel drop filters. Numerical simulations
      demonstrate that these filters exhibit ideal transfer characteristics.

PMID- 19381232
TI  - Novel approach to photonic bands with frequency-dependent dielectric constants.
AB  - We formulated a novel method to calculate the dispersion relations of arbitrary
      photonic crystals with frequency-dependent dielectric constants based on the
      numerical simulation of dipole radiation. As an example, we applied this method
      to a two-dimensional square lattice of metallic cylinders and obtained a good
      agreement with the previous result by means of the plane-wave expansion method by
      Kuzmiak et al. [Phys. Rev. B 50, 16 835 (1994)]. In addition to the dispersion
      relations, we could obtain the symmetries and the wave functions of the
      eigenmodes.

PMID- 19381233
TI  - Eigenmode symmetry for simple cubic lattices and the transmission spectra.
AB  - The existence of uncoupled modes is identified by gaps in the transmission
      spectra when the density of states is nonzero. We use a group theoretic analysis
      of the photonic band structure for a simple cubic lattice to tag the symmetry and
      polarization of each band. The results are compared with transmission spectra
      calculated by the transfer matrix method.

PMID- 19381234
TI  - Dynamic cross-waveguide optical switching with a nonlinear photonic band-gap
      structure.
AB  - We present a numerical study of a two dimensional all- optical switching device
      which consists of two crossed waveguides and a nonlinear photonic band{gap
      structure in the center. The switching mechanism is based on a dynamic shift of
      the photonic band edge by means of a strong pump pulse and is modeled on the
      basis of a two dimensional finite volume time domain method. With our arrangement
      we find a pronounced optical switching effect in which due to the cross-waveguide
      geometry the overlay of the probe beam by a pump pulse is significantly reduced.

PMID- 19381235
TI  - Applications of holographic interferometryto structural and dynamic analysis of
      anadvanced graphite-epoxy compositecomponent.
AB  - It was undertaken to apply holographic techniques to char- acterize the dynamic
      behavior and structure of an advanced graphite-epoxy composite part and its
      ancillary mounting geometry. Holograms of the vibrational modes of the structure
      are used to accurately map the nodes, maxima, minima, and geometry of the induced
      motion. Holograms of the displacement patterns of mechanical and thermally
      induced stress in the structure are also used to map the location and extent of
      nonuniformities, discontinuities, and micro-structural defects in the volume and
      mounting of the composite material. Holographic data was imaged by a photo
      thermoplastic based holocamera system configured for off-axis holograms and
      coupled to high resolution video capture for subsequent image analysis.

PMID- 19381238
TI  - Introduction.
AB  - Homogeneous, periodic, quasiperiodic, irregular and disordered spatial structures
      have been at the heart of scientific interest and research for a long time and in
      many disciplines as diverse as chemistry, physics, biology and morphology. Some
      recent, spectacular achievements in experimental quantum optics have, however,
      made it possible to study quantum effects in a variety of spatial structures. The
      main aim of this Focus Issue is to present some of the most recent theoretical,
      numerical and experimental progresses in the area of Quantum Structures, i.e.
      spatial structures that display quantum features. A short background overview of
      Quantum Structures is provided at the beginning of this Focus Issue, in which
      individual authors' works are specifically commented. In brief, we can say that
      the articles can be catalogued into two main areas of research interest in
      Quantum Structures: quantum effects in spatial structures in nonlinear optics,
      and in atomic physics.

PMID- 19381239
TI  - Quantum structures in nonlinear optics and atomic physics: a background overview.
AB  - A brief overview of quantum effects in spatial structures such as nonlinear
      optical patterns, chains of trapped ions and atoms in optical lattices is
      presented. Some of the main results of the contributions to this Focus Issue are
      also briefly described.

PMID- 19381240
TI  - Growth dynamics of noise-sustained structures in nonlinear optical resonators.
AB  - The existence of macroscopic noise-sustained structures in nonlinear optics is
      theoretically predicted and numerically observed, in the regime of convective
      instability. The advection-like term, necessary to turn the instability to
      convective for the parameter region where advection overwhelms the growth, can
      stem from pump beam tilting or birefringence induced walk-off. The growth
      dynamics of both noise-sustained and deterministic patterns is exemplified by
      means of movies. This allows to observe the process of formation of these
      structures and to confirm the analytical predictions. The amplification of
      quantum noise by several orders of magnitude is predicted. The qualitative
      analysis of the near- and far-field is given. It suffices to distinguish noise
      sustained from deterministic structures; quantitative informations can be
      obtained in terms of the statistical properties of the spectra.

PMID- 19381241
TI  - Spatial patterns in optical parametric oscillators with spherical mirrors:
      classical and quantum effects.
AB  - We investigate the formation of transverse patterns in a doubly resonant
      degenerate optical parametric oscillator. Extending previous work, we treat the
      more realistic case of a spherical mirror cavity with a finite-sized input pump
      field. Using numerical simulations in real space, we determine the conditions on
      the cavity geometry, pump size and detunings for which pattern formation occurs;
      we find multistability of different types of optical patterns. Below threshold,
      we analyze the dependence of the quantum image on the width of the input field,
      in the near and in the far field.

PMID- 19381242
TI  - Spatial correlations of spontaneously down-converted photon pairs detected with a
      single-photon-sensitive CCD camera.
AB  - A single-photon-sensitive intensified charge-coupled-device (ICCD) camera has
      been used to simultaneously detect, over a broad area, degenerate and
      nondegenerate photon pairs generated by the quantum-optical process of
      spontaneous parametric down-conversion. We have developed a new method for
      determining the quantum fourth- order correlations in spatially extended
      detection systems such as this one. Our technique reveals the expected phase
      matching-induced spa- tial correlations in a 2-f Fourier-transform system.

PMID- 19381243
TI  - Coherent excitation of normal modes in a string of Ca+ ions.
AB  - Crystal structures of Calcium ions have been prepared in a linear Paul trap and
      their collective motion excited with resonant rf-fields. The trapped ions are
      laser-cooled and images of the fluorescing ions are obtained with a CCD camera
      and show high spatial resolution. Crystals with up to 15 ions arrange in a linear
      string and their eigenmodes can subsequently be selectively excited. The
      collective motion of the string can then be observed via the CCD images.ons
      arrange in a linear string and their eigen-modes can subsequently be selectively
      excited. The collective motion of the string can then be observed via the CCD
      images.

PMID- 19381244
TI  - Diffusion of a single ion in a one-dimensional optical lattice.
AB  - We present an experimental study of the spatial diffusion of a single ion in a
      polarization gradient field. A 24 Mg + ion was radially confined in a two
      dimensional radio-frequency (rf) trap, while an optical lattice superimposed to a
      weak electric potential was applied along the free axis. With the help of a
      statistical analysis of single ion trajectories, a spatial diffusion constant was
      obtained as a function of optical potential depth. The results are compared to
      semiclassical theoretical models for trapped ions and neutral atoms.

PMID- 19381245
TI  - Enhancement of laser CT image contrast by correction of artifacts due to surface
      effects.
AB  - Mismatched boundary conditions such as air-sample interface introduce artifacts
      that obscure internal information in the reconstructed laser computed tomographic
      (CT) images. Here, we demonstrate enhancement of target structure in the laser CT
      images by correcting the projection data using the experimentally determined
      angle dependence of sample surface attenuation. The images reconstructed with the
      corrected projection data are shown to have improved image contrast. Our proposed
      correction to laser CT reconstruction is effective for visualizing internal
      structure with small variations in the attenuation coefficients that would
      otherwise be masked by the dominant surface attenuation.

PMID- 19381246
TI  - A magneto-optical trap loaded from a pyramidal funnel.
AB  - We have demonstrated the transfer of 39 K and 40 K atoms from a magneto-optical
      funnel (a hollow pyramidal mirror) through a low (0:05 l/s) conductance hole and
      into a conventional magneto-optical trap (mot) 35 cm away, with an efficiency of
      approximately six percent. This simple scheme should be useful for experiments
      requiring high loading rates with minimal contamination from hot untrapped atoms.

PMID- 19381247
TI  - Diffuse optical reflection tomography using continuous wave illumination.
AB  - Diffuse optical reflection tomography is used to reconstruct absorption images
      from continuous-wave measurements of diffuse light re-emitted from a "semi
      infinite" medium. The imaging algorithm is simple and fast and permits psuedo-3D
      images to be reconstructed from measurements made with a single source of light.
      Truly quantitative three-dimensional images will require modifications to the
      algorithm, such as incorporating measurements from multiple sources.

PMID- 19381248
TI  - Quantum control of non-circular Trojan states in hydrogen.
AB  - Control of non-circular and non-spreading wave packet states by a resonant
      radiation field is predicted and numerically confirmed for hydrogen.

PMID- 19381250
TI  - Phoenix is required for mechanosensory hair cell regeneration in the zebrafish
      lateral line.
AB  - In humans, the absence or irreversible loss of hair cells, the sensory
      mechanoreceptors in the cochlea, accounts for a large majority of acquired and
      congenital hearing disorders. In the auditory and vestibular neuroepithelia of
      the inner ear, hair cells are accompanied by another cell type called supporting
      cells. This second cell population has been described as having stem cell-like
      properties, allowing efficient hair cell replacement during embryonic and
      larval/fetal development of all vertebrates. However, mammals lose their
      regenerative capacity in most inner ear neuroepithelia in postnatal life.
      Remarkably, reptiles, birds, amphibians, and fish are different in that they can
      regenerate hair cells throughout their lifespan. The lateral line in amphibians
      and in fish is an additional sensory organ, which is used to detect water
      movements and is comprised of neuroepithelial patches, called neuromasts. These
      are similar in ultra-structure to the inner ear's neuroepithelia and they share
      the expression of various molecular markers. We examined the regeneration process
      in hair cells of the lateral line of zebrafish larvae carrying a retroviral
      integration in a previously uncharacterized gene, phoenix (pho). Phoenix mutant
      larvae develop normally and display a morphologically intact lateral line.
      However, after ablation of hair cells with copper or neomycin, their regeneration
      in pho mutants is severely impaired. We show that proliferation in the supporting
      cells is strongly decreased after damage to hair cells and correlates with the
      reduction of newly formed hair cells in the regenerating phoenix mutant
      neuromasts. The retroviral integration linked to the phenotype is in a novel gene
      with no known homologs showing high expression in neuromast supporting cells.
      Whereas its role during early development of the lateral line remains to be
      addressed, in later larval stages phoenix defines a new class of proteins
      implicated in hair cell regeneration.

PMID- 19381251
TI  - Effective but costly, evolved mechanisms of defense against a virulent
      opportunistic pathogen in Drosophila melanogaster.
AB  - Drosophila harbor substantial genetic variation for antibacterial defense, and
      investment in immunity is thought to involve a costly trade-off with life history
      traits, including development, life span, and reproduction. To understand the way
      in which insects invest in fighting bacterial infection, we selected for survival
      following systemic infection with the opportunistic pathogen Pseudomonas
      aeruginosa in wild-caught Drosophila melanogaster over 10 generations. We then
      examined genome-wide changes in expression in the selected flies relative to
      unselected controls, both of which had been infected with the pathogen. This
      powerful combination of techniques allowed us to specifically identify the
      genetic basis of the evolved immune response. In response to selection,
      population-level survivorship to infection increased from 15% to 70%. The evolved
      capacity for defense was costly, however, as evidenced by reduced longevity and
      larval viability and a rapid loss of the trait once selection pressure was
      removed. Counter to expectation, we observed more rapid developmental rates in
      the selected flies. Selection-associated changes in expression of genes with dual
      involvement in developmental and immune pathways suggest pleiotropy as a possible
      mechanism for the positive correlation. We also found that both the Toll and the
      Imd pathways work synergistically to limit infectivity and that cellular immunity
      plays a more critical role in overcoming P. aeruginosa infection than previously
      reported. This work reveals novel pathways by which Drosophila can survive
      infection with a virulent pathogen that may be rare in wild populations, however,
      due to their cost.

PMID- 19381252
TI  - High throughput functional assays of the variant antigen PfEMP1 reveal a single
      domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high
      affinity and is targeted by naturally acquired neutralizing antibodies.
AB  - Plasmodium falciparum-infected erythrocytes bind endothelial receptors to
      sequester in vascular beds, and binding to ICAM1 has been implicated in cerebral
      malaria. Binding to ICAM1 may be mediated by the variant surface antigen family
      PfEMP1: for example, 6 of 21 DBLbetaC2 domains from the IT4 strain PfEMP1
      repertoire were shown to bind ICAM1, and the PfEMP1 containing these 6 domains
      are all classified as Group B or C type. In this study, we surveyed binding of
      ICAM1 to 16 DBLbetaC2 domains of the 3D7 strain PfEMP1 repertoire, using a high
      throughput Bioplex assay format. Only one DBL2betaC2 domain from the Group A
      PfEMP1 PF11_0521 showed strong specific binding. Among these 16 domains,
      DBL2betaC2(PF11_0521) best preserved the residues previously identified as
      conserved in ICAM1-binding versus non-binding domains. Our analyses further
      highlighted the potential role of conserved residues within predominantly non
      conserved flexible loops in adhesion, and, therefore, as targets for
      intervention. Our studies also suggest that the structural/functional DBLbetaC2
      domain involved in ICAM1 binding includes about 80 amino acid residues upstream
      of the previously suggested DBLbetaC2 domain. DBL2betaC2(PF11_0521) binding to
      ICAM1 was inhibited by immune sera from east Africa but not by control US sera.
      Neutralizing antibodies were uncommon in children but common in immune adults
      from east Africa. Inhibition of binding was much more efficient than reversal of
      binding, indicating a strong interaction between DBL2betaC2(PF11_0521) and ICAM1.
      Our high throughput approach will significantly accelerate studies of PfEMP1
      binding domains and protective antibody responses.

PMID- 19381253
TI  - A herpesvirus encoded deubiquitinase is a novel neuroinvasive determinant.
AB  - The neuroinvasive property of several alpha-herpesviruses underlies an uncommon
      infectious process that includes the establishment of life-long latent infections
      in sensory neurons of the peripheral nervous system. Several herpesvirus proteins
      are required for replication and dissemination within the nervous system,
      indicating that exploiting the nervous system as a niche for productive infection
      requires a specialized set of functions encoded by the virus. Whether initial
      entry into the nervous system from peripheral tissues also requires specialized
      viral functions is not known. Here we show that a conserved deubiquitinase domain
      embedded within a pseudorabies virus structural protein, pUL36, is essential for
      initial neural invasion, but is subsequently dispensable for transmission within
      and between neurons of the mammalian nervous system. These findings indicate that
      the deubiquitinase contributes to neurovirulence by participating in a previously
      unrecognized initial step in neuroinvasion.

PMID- 19381254
TI  - Deletions in the repertoire of Pseudomonas syringae pv. tomato DC3000 type III
      secretion effector genes reveal functional overlap among effectors.
AB  - The gamma-proteobacterial plant pathogen Pseudomonas syringae pv. tomato DC3000
      uses the type III secretion system to inject ca. 28 Avr/Hop effector proteins
      into plants, which enables the bacterium to grow from low inoculum levels to
      produce bacterial speck symptoms in tomato, Arabidopsis thaliana, and (when
      lacking hopQ1-1) Nicotiana benthamiana. The effectors are collectively essential
      but individually dispensable for the ability of the bacteria to defeat defenses,
      grow, and produce symptoms in plants. Eighteen of the effector genes are
      clustered in six genomic islands/islets. Combinatorial deletions involving these
      clusters and two of the remaining effector genes revealed a redundancy-based
      structure in the effector repertoire, such that some deletions diminished growth
      in N. benthamiana only in combination with other deletions. Much of the ability
      of DC3000 to grow in N. benthamiana was found to be due to five effectors in two
      redundant-effector groups (REGs), which appear to separately target two high
      level processes in plant defense: perception of external pathogen signals (AvrPto
      and AvrPtoB) and deployment of antimicrobial factors (AvrE, HopM1, HopR1).
      Further support for the membership of HopR1 in the same REG as AvrE was gained
      through bioinformatic analysis, revealing the existence of an AvrE/DspA/E/HopR
      effector superfamily, which has representatives in virtually all groups of
      proteobacterial plant pathogens that deploy type III effectors.

PMID- 19381255
TI  - Rapid and accurate multiple testing correction and power estimation for millions
      of correlated markers.
AB  - With the development of high-throughput sequencing and genotyping technologies,
      the number of markers collected in genetic association studies is growing
      rapidly, increasing the importance of methods for correcting for multiple
      hypothesis testing. The permutation test is widely considered the gold standard
      for accurate multiple testing correction, but it is often computationally
      impractical for these large datasets. Recently, several studies proposed
      efficient alternative approaches to the permutation test based on the
      multivariate normal distribution (MVN). However, they cannot accurately correct
      for multiple testing in genome-wide association studies for two reasons. First,
      these methods require partitioning of the genome into many disjoint blocks and
      ignore all correlations between markers from different blocks. Second, the true
      null distribution of the test statistic often fails to follow the asymptotic
      distribution at the tails of the distribution. We propose an accurate and
      efficient method for multiple testing correction in genome-wide association
      studies--SLIDE. Our method accounts for all correlation within a sliding window
      and corrects for the departure of the true null distribution of the statistic
      from the asymptotic distribution. In simulations using the Wellcome Trust Case
      Control Consortium data, the error rate of SLIDE's corrected p-values is more
      than 20 times smaller than the error rate of the previous MVN-based methods'
      corrected p-values, while SLIDE is orders of magnitude faster than the
      permutation test and other competing methods. We also extend the MVN framework to
      the problem of estimating the statistical power of an association study with
      correlated markers and propose an efficient and accurate power estimation method
      SLIP. SLIP and SLIDE are available at http://slide.cs.ucla.edu.

PMID- 19381256
TI  - Adventures in semantic publishing: exemplar semantic enhancements of a research
      article.
AB  - Scientific innovation depends on finding, integrating, and re-using the products
      of previous research. Here we explore how recent developments in Web technology,
      particularly those related to the publication of data and metadata, might assist
      that process by providing semantic enhancements to journal articles within the
      mainstream process of scholarly journal publishing. We exemplify this by
      describing semantic enhancements we have made to a recent biomedical research
      article taken from PLoS Neglected Tropical Diseases, providing enrichment to its
      content and increased access to datasets within it. These semantic enhancements
      include provision of live DOIs and hyperlinks; semantic markup of textual terms,
      with links to relevant third-party information resources; interactive figures; a
      re-orderable reference list; a document summary containing a study summary, a tag
      cloud, and a citation analysis; and two novel types of semantic enrichment: the
      first, a Supporting Claims Tooltip to permit "Citations in Context", and the
      second, Tag Trees that bring together semantically related terms. In addition, we
      have published downloadable spreadsheets containing data from within tables and
      figures, have enriched these with provenance information, and have demonstrated
      various types of data fusion (mashups) with results from other research articles
      and with Google Maps. We have also published machine-readable RDF metadata both
      about the article and about the references it cites, for which we developed a
      Citation Typing Ontology, CiTO (http://purl.org/net/cito/). The enhanced article,
      which is available at http://dx.doi.org/10.1371/journal.pntd.0000228.x001,
      presents a compelling existence proof of the possibilities of semantic
      publication. We hope the showcase of examples and ideas it contains, described in
      this paper, will excite the imaginations of researchers and publishers,
      stimulating them to explore the possibilities of semantic publishing for their
      own research articles, and thereby break down present barriers to the discovery
      and re-use of information within traditional modes of scholarly communication.

PMID- 19381257
TI  - Pre-micro RNA signatures delineate stages of endothelial cell transformation in
      Kaposi sarcoma.
AB  - MicroRNAs (miRNA) have emerged as key regulators of cell lineage differentiation
      and cancer. We used precursor miRNA profiling by a novel real-time QPCR method
      (i) to define progressive stages of endothelial cell transformation cumulating in
      Kaposi sarcoma (KS) and (ii) to identify specific miRNAs that serve as biomarkers
      for tumor progression. We were able to compare primary patient biopsies to well
      established culture and mouse tumor models. Loss of mir-221 and gain of mir-15
      expression demarked the transition from merely immortalized to fully tumorigenic
      endothelial cells. Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs
      increased linearly with the degree of transformation. Mir-24 emerged as a
      biomarker specific for KS.

PMID- 19381258
TI  - Early onset prion disease from octarepeat expansion correlates with copper
      binding properties.
AB  - Insertional mutations leading to expansion of the octarepeat domain of the prion
      protein (PrP) are directly linked to prion disease. While normal PrP has four
      PHGGGWGQ octapeptide segments in its flexible N-terminal domain, expanded forms
      may have up to nine additional octapeptide inserts. The type of prion disease
      segregates with the degree of expansion. With up to four extra octarepeats, the
      average onset age is above 60 years, whereas five to nine extra octarepeats
      results in an average onset age between 30 and 40 years, a difference of almost
      three decades. In wild-type PrP, the octarepeat domain takes up copper (Cu(2+))
      and is considered essential for in vivo function. Work from our lab demonstrates
      that the copper coordination mode depends on the precise ratio of Cu(2+) to
      protein. At low Cu(2+) levels, coordination involves histidine side chains from
      adjacent octarepeats, whereas at high levels each repeat takes up a single copper
      ion through interactions with the histidine side chain and neighboring backbone
      amides. Here we use both octarepeat constructs and recombinant PrP to examine how
      copper coordination modes are influenced by octarepeat expansion. We find that
      there is little change in affinity or coordination mode populations for
      octarepeat domains with up to seven segments (three inserts). However, domains
      with eight or nine total repeats (four or five inserts) become energetically
      arrested in the multi-histidine coordination mode, as dictated by higher copper
      uptake capacity and also by increased binding affinity. We next pooled all
      published cases of human prion disease resulting from octarepeat expansion and
      find remarkable agreement between the sudden length-dependent change in copper
      coordination and onset age. Together, these findings suggest that either loss of
      PrP copper-dependent function or loss of copper-mediated protection against PrP
      polymerization makes a significant contribution to early onset prion disease.

PMID- 19381259
TI  - A novel bocavirus associated with acute gastroenteritis in Australian children.
AB  - Acute gastroenteritis (AGE) is a common illness affecting all age groups
      worldwide, causing an estimated three million deaths annually. Viruses such as
      rotavirus, adenovirus, and caliciviruses are a major cause of AGE, but in many
      patients a causal agent cannot be found despite extensive diagnostic testing.
      Proposing that novel viruses are the reason for this diagnostic gap, we used
      molecular screening to investigate a cluster of undiagnosed cases that were part
      of a larger case control study into the etiology of pediatric AGE. Degenerate
      oligonucleotide primed (DOP) PCR was used to non-specifically amplify viral DNA
      from fecal specimens. The amplified DNA was then cloned and sequenced for
      analysis. A novel virus was detected. Elucidation and analysis of the genome
      indicates it is a member of the Bocavirus genus of the Parvovirinae, 23% variant
      at the nucleotide level from its closest formally recognized relative, the Human
      Bocavirus (HBoV), and similar to the very recently proposed second species of
      Bocavirus (HBoV2). Fecal samples collected from case control pairs during 2001
      for the AGE study were tested with a bocavirus-specific PCR, and HBoV2 (sequence
      confirmed) was detected in 32 of 186 cases with AGE (prevalence 17.2%) compared
      with only 15 controls (8.1%). In this same group of children, HBoV2 prevalence
      was exceeded only by rotavirus (39.2%) and astrovirus (21.5%) and was more
      prevalent than norovirus genogroup 2 (13.4%) and adenovirus (4.8%). In a
      univariate analysis of the matched pairs (McNemar's Test), the odds ratio for the
      association of AGE with HBoV2 infection was 2.6 (95% confidence interval 1.2
      5.7); P = 0.007. During the course of this screening, a second novel bocavirus
      was detected which we have designated HBoV species 3 (HBoV3). The prevalence of
      HBoV3 was low (2.7%), and it was not associated with AGE. HBoV2 and HBoV3 are
      newly discovered bocaviruses, of which HBoV2 is the thirdmost-prevalent virus,
      after rotavirus and astrovirus, associated with pediatric AGE in this study.

PMID- 19381260
TI  - A critical role for CD8 T cells in a nonhuman primate model of tuberculosis.
AB  - The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown,
      and studies of CD8 T cell-mediated protection against tuberculosis in mice have
      yielded controversial results. Unlike mice, humans and nonhuman primates share a
      number of important features of the immune system that relate directly to the
      specificity and functions of CD8 T cells, such as the expression of group 1 CD1
      proteins that are capable of presenting Mycobacterium tuberculosis lipids
      antigens and the cytotoxic/bactericidal protein granulysin. Employing a more
      relevant nonhuman primate model of human tuberculosis, we examined the
      contribution of BCG- or M. tuberculosis-elicited CD8 T cells to vaccine-induced
      immunity against tuberculosis. CD8 depletion compromised BCG vaccine-induced
      immune control of M. tuberculosis replication in the vaccinated rhesus macaques.
      Depletion of CD8 T cells in BCG-vaccinated rhesus macaques led to a significant
      decrease in the vaccine-induced immunity against tuberculosis. Consistently,
      depletion of CD8 T cells in rhesus macaques that had been previously infected
      with M. tuberculosis and cured by antibiotic therapy also resulted in a loss of
      anti-tuberculosis immunity upon M. tuberculosis re-infection. The current study
      demonstrates a major role for CD8 T cells in anti-tuberculosis immunity, and
      supports the view that CD8 T cells should be included in strategies for
      development of new tuberculosis vaccines and immunotherapeutics.

PMID- 19381261
TI  - A novel role for Stat1 in phagosome acidification and natural host resistance to
      intracellular infection by Leishmania major.
AB  - Intracellular parasites of the genus Leishmania generate severe diseases in
      humans, which are associated with a failure of the infected host to induce a
      protective interferon gamma (IFNgamma)-mediated immune response. We tested the
      role of the JAK/STAT1 signaling pathway in Leishmania pathogenesis by utilizing
      knockout mice lacking the signal transducer and activator of transcription 1
      (Stat1) and derived macrophages. Unexpectedly, infection of Stat1-deficient
      macrophages in vitro with promastigotes from Leishmania major and attenuated LPG1
      knockout mutants (lpg(-)) specifically lacking lipophosphoglycan (LPG) resulted
      in a twofold increased intracellular growth, which was independent of IFNgamma
      and associated with a substantial increase in phagosomal pH. Phagosomes in Stat1
      /- macrophages showed normal maturation as judged by the accumulation of the
      lysosomal marker protein rab7, and provided normal vATPase activity, but were
      defective in the anion conductive pathway required for full vesicular
      acidification. Our results suggest a role of acidic pH in the control of
      intracellular Leishmania growth early during infection and identify for the first
      time an unexpected role of Stat1 in natural anti-microbial resistance independent
      from its function as IFNgamma-induced signal transducer. This novel Stat1
      function may have important implications to studies of other pathogens, as the
      acidic phagolysosomal pH plays an important role in antigen processing and the
      uncoating process of many viruses.

PMID- 19381262
TI  - Retnla (relmalpha/fizz1) suppresses helminth-induced Th2-type immunity.
AB  - Retnla (Resistin-like molecule alpha/FIZZ1) is induced during Th2 cytokine immune
      responses. However, the role of Retnla in Th2-type immunity is unknown. Here,
      using Retnla(-/-) mice and three distinct helminth models, we show that Retnla
      functions as a negative regulator of Th2 responses. Pulmonary granuloma formation
      induced by the eggs of the helminth parasite Schistosoma mansoni is dependent on
      IL-4 and IL-13 and associated with marked increases in Retnla expression. We
      found that both primary and secondary pulmonary granuloma formation were
      exacerbated in the absence of Retlna. The number of granuloma-associated
      eosinophils and serum IgE titers were also enhanced. Moreover, when chronically
      infected with S. mansoni cercariae, Retnla(-/-) mice displayed significant
      increases in granulomatous inflammation in the liver and the development of
      fibrosis and progression to hepatosplenic disease was markedly augmented.
      Finally, Retnla(-/-) mice infected with the gastrointestinal (GI) parasite
      Nippostrongylus brasiliensis had intensified lung pathology to migrating larvae,
      reduced fecundity, and accelerated expulsion of adult worms from the intestine,
      suggesting Th2 immunity was enhanced. When their immune responses were compared,
      helminth infected Retnla(-/-) mice developed stronger Th2 responses, which could
      be reversed by exogenous rRelmalpha treatment. Studies with several cytokine
      knockout mice showed that expression of Retnla was dependent on IL-4 and IL-13
      and inhibited by IFN-gamma, while tissue localization and cell isolation
      experiments indicated that eosinophils and epithelial cells were the primary
      producers of Retnla in the liver and lung, respectively. Thus, the Th2-inducible
      gene Retnla suppresses resistance to GI nematode infection, pulmonary
      granulomatous inflammation, and fibrosis by negatively regulating Th2-dependent
      responses.

PMID- 19381263
TI  - Evidence for antisense transcription associated with microRNA target mRNAs in
      Arabidopsis.
AB  - Antisense transcription is a pervasive phenomenon, but its source and functional
      significance is largely unknown. We took an expression-based approach to explore
      microRNA (miRNA)-related antisense transcription by computational analyses of
      published whole-genome tiling microarray transcriptome and deep sequencing small
      RNA (smRNA) data. Statistical support for greater abundance of antisense
      transcription signatures and smRNAs was observed for miRNA targets than for
      paralogous genes with no miRNA cleavage site. Antisense smRNAs were also found
      associated with MIRNA genes. This suggests that miRNA-associated "transitivity"
      (production of small interfering RNAs through antisense transcription) is more
      common than previously reported. High-resolution (3 nt) custom tiling microarray
      transcriptome analysis was performed with probes 400 bp 5' upstream and 3'
      downstream of the miRNA cleavage sites (direction relative to the mRNA) for 22
      select miRNA target genes. We hybridized RNAs labeled from the smRNA pathway
      mutants, including hen1-1, dcl1-7, hyl1-2, rdr6-15, and sgs3-14. Results showed
      that antisense transcripts associated with miRNA targets were mainly elevated in
      hen1-1 and sgs3-14 to a lesser extent, and somewhat reduced in dcl11-7, hyl11-2,
      or rdr6-15 mutants. This was corroborated by semi-quantitative reverse
      transcription PCR; however, a direct correlation of antisense transcript
      abundance in MIR164 gene knockouts was not observed. Our overall analysis reveals
      a more widespread role for miRNA-associated transitivity with implications for
      functions of antisense transcription in gene regulation. HEN1 and SGS3 may be
      links for miRNA target entry into different RNA processing pathways.

PMID- 19381264
TI  - Inferring stabilizing mutations from protein phylogenies: application to
      influenza hemagglutinin.
AB  - One selection pressure shaping sequence evolution is the requirement that a
      protein fold with sufficient stability to perform its biological functions. We
      present a conceptual framework that explains how this requirement causes the
      probability that a particular amino acid mutation is fixed during evolution to
      depend on its effect on protein stability. We mathematically formalize this
      framework to develop a Bayesian approach for inferring the stability effects of
      individual mutations from homologous protein sequences of known phylogeny. This
      approach is able to predict published experimentally measured mutational
      stability effects (DeltaDeltaG values) with an accuracy that exceeds both a state
      of-the-art physicochemical modeling program and the sequence-based consensus
      approach. As a further test, we use our phylogenetic inference approach to
      predict stabilizing mutations to influenza hemagglutinin. We introduce these
      mutations into a temperature-sensitive influenza virus with a defect in its
      hemagglutinin gene and experimentally demonstrate that some of the mutations
      allow the virus to grow at higher temperatures. Our work therefore describes a
      powerful new approach for predicting stabilizing mutations that can be
      successfully applied even to large, complex proteins such as hemagglutinin. This
      approach also makes a mathematical link between phylogenetics and experimentally
      measurable protein properties, potentially paving the way for more accurate
      analyses of molecular evolution.

PMID- 19381265
TI  - Allosteric transitions of supramolecular systems explored by network models:
      application to chaperonin GroEL.
AB  - Identification of pathways involved in the structural transitions of biomolecular
      systems is often complicated by the transient nature of the conformations visited
      across energy barriers and the multiplicity of paths accessible in the
      multidimensional energy landscape. This task becomes even more challenging in
      exploring molecular systems on the order of megadaltons. Coarse-grained models
      that lend themselves to analytical solutions appear to be the only possible means
      of approaching such cases. Motivated by the utility of elastic network models for
      describing the collective dynamics of biomolecular systems and by the growing
      theoretical and experimental evidence in support of the intrinsic accessibility
      of functional substates, we introduce a new method, adaptive anisotropic network
      model (aANM), for exploring functional transitions. Application to bacterial
      chaperonin GroEL and comparisons with experimental data, results from action
      minimization algorithm, and previous simulations support the utility of aANM as a
      computationally efficient, yet physically plausible, tool for unraveling
      potential transition pathways sampled by large complexes/assemblies. An important
      outcome is the assessment of the critical inter-residue interactions
      formed/broken near the transition state(s), most of which involve conserved
      residues.

PMID- 19381266
TI  - Pedagogies of engagement in science: A comparison of PBL, POGIL, and PLTL*
AB  - Problem-based learning, process-oriented guided inquiry learning, and peer-led
      team learning are student-centered, active-learning pedagogies commonly used in
      science education. The characteristic features of each are compared and
      contrasted to enable new practitioners to decide which approach or combination of
      approaches will suit their particular situation.

PMID- 19381267
TI  - Design principles for riboswitch function.
AB  - Scientific and technological advances that enable the tuning of integrated
      regulatory components to match network and system requirements are critical to
      reliably control the function of biological systems. RNA provides a promising
      building block for the construction of tunable regulatory components based on its
      rich regulatory capacity and our current understanding of the sequence-function
      relationship. One prominent example of RNA-based regulatory components is
      riboswitches, genetic elements that mediate ligand control of gene expression
      through diverse regulatory mechanisms. While characterization of natural and
      synthetic riboswitches has revealed that riboswitch function can be modulated
      through sequence alteration, no quantitative frameworks exist to investigate or
      guide riboswitch tuning. Here, we combined mathematical modeling and experimental
      approaches to investigate the relationship between riboswitch function and
      performance. Model results demonstrated that the competition between reversible
      and irreversible rate constants dictates performance for different regulatory
      mechanisms. We also found that practical system restrictions, such as an upper
      limit on ligand concentration, can significantly alter the requirements for
      riboswitch performance, necessitating alternative tuning strategies. Previous
      experimental data for natural and synthetic riboswitches as well as experiments
      conducted in this work support model predictions. From our results, we developed
      a set of general design principles for synthetic riboswitches. Our results also
      provide a foundation from which to investigate how natural riboswitches are tuned
      to meet systems-level regulatory demands.

PMID- 19381268
TI  - A bipolar clamp mechanism for activation of Jak-family protein tyrosine kinases.
AB  - Most cell surface receptors for growth factors and cytokines dimerize in order to
      mediate signal transduction. For many such receptors, the Janus kinase (Jak)
      family of non-receptor protein tyrosine kinases are recruited in pairs and
      juxtaposed by dimerized receptor complexes in order to activate one another by
      trans-phosphorylation. An alternative mechanism for Jak trans-phosphorylation has
      been proposed in which the phosphorylated kinase interacts with the Src homology
      2 (SH2) domain of SH2-B, a unique adaptor protein with the capacity to homo
      dimerize. Building on a rule-based kinetic modeling approach that considers the
      concerted nature and combinatorial complexity of modular protein domain
      interactions, we examine these mechanisms in detail, focusing on the growth
      hormone (GH) receptor/Jak2/SH2-Bbeta system. The modeling results suggest that,
      whereas Jak2-(SH2-Bbeta)(2)-Jak2 heterotetramers are scarcely expected to affect
      Jak2 phosphorylation, SH2-Bbeta and dimerized receptors synergistically promote
      Jak2 trans-activation in the context of intracellular signaling. Analysis of the
      results revealed a unique mechanism whereby SH2-B and receptor dimers constitute
      a bipolar 'clamp' that stabilizes the active configuration of two Jak2 molecules
      in the same macro-complex.

PMID- 19381269
TI  - Relationships between specific airway resistance and forced expiratory flows in
      asthmatic children.
AB  - BACKGROUND: The earliest changes associated with airflow obstruction in asthmatic
      children are a proportionally greater reduction in FEF(50%) than in FEV(1) using
      spirometry, and an increase in specific airway resistance (sRaw) using body
      plethysmography. Consequently, we hypothesized that sRaw could be better linked
      to FEF(50%) than to FEV(1). The first aim was to assess the relationships between
      forced expiratory flows and sRaw in a large group of asthmatic children in a
      transversal study. We then performed a longitudinal study in order to determine
      whether sRaw of preschool children could predict subsequent impairment of forced
      expiratory flows at school age. METHODOLOGY: Pulmonary function tests (sRaw and
      forced expiratory flows) of 2193 asthmatic children were selected for a
      transversal analysis, while 365 children were retrospectively selected for
      longitudinal assessment from preschool to school age. PRINCIPAL FINDINGS: The
      transversal data showed that sRaw is differently related to FEF(50%) (-1/sRaw)
      and to FEV(1) (near linearly). These results were further explained by a simple
      one-compartment lung model, which justified the shape of the observed
      relationships. As hypothesized, sRaw correlated more strongly to FEF(50%) than to
      FEV(1) (r = -0.64 versus -0.39, respectively; p<0.001). In the longitudinal part
      of the study, sRaw at preschool age correlated with subsequent FEF(50%) (%
      predicted) (-0.31, 95% CI, -0.40 to -0.22), but weakly with subsequent FEV(1) (%
      predicted) (-0.09, 95% CI, -0.20 to 0). CONCLUSION: Specific Raw is more strongly
      related to FEF(50%) than to FEV(1) and could be used in preschool children to
      predict subsequent mild airflow limitation.

PMID- 19381270
TI  - Estimating the capacity for ART provision in Tanzania with the use of data on
      staff productivity and patient losses.
AB  - BACKGROUND: International targets for access to antiretroviral therapy (ART) have
      over-estimated the capacity of health systems in low-income countries in Sub
      Saharan Africa. The WHO target for number on treatment by end 2005 for Tanzania
      was 10 times higher than actually achieved. The target of the national Care and
      Treatment Plan (CTP) was also not reached. We aimed at estimating the capacity
      for ART provision and created five scenarios for ART production given existing
      resource limitations. METHODS: A situation analysis including scrutiny of staff
      factors, such as available data on staff and patient factors including access to
      ART and patient losses, made us conclude that the lack of clinical staff is the
      main limiting factor for ART scale-up, assuming that sufficient drugs and
      supplies are provided by donors. We created a simple formula to estimate the
      number of patients on ART based on availability and productivity of clinical
      staff, time needed to initiate vs maintain a patient on ART and patient losses
      using five different scenarios with varying levels of these parameters. FINDINGS:
      Our scenario assuming medium productivity (40% higher than that observed in 2002)
      and medium loss of patients (20% in addition to 15% first-year mortality)
      coincides with the actual reported number of patients initiated on ART up to
      2008, but is considerably below the national CTP target of 90% coverage for 2009,
      corresponding to 420,000 on ART and 710,000 life-years saved (LY's). Our analysis
      suggests that a coverage of 40% or 175,000 on treatment and 350,000 LY's saved is
      more achievable. CONCLUSION: A comparison of our scenario estimations and actual
      output 2006-2008 indicates that a simple user-friendly dynamic model can estimate
      the capacity for ART scale-up in resource-poor settings based on identification
      of a limiting staff factor and information on availability of this staff and
      patient losses. Thus, it is possible to set more achievable targets.

PMID- 19381271
TI  - End-tagging of ultra-short antimicrobial peptides by W/F stretches to facilitate
      bacterial killing.
AB  - BACKGROUND: Due to increasing resistance development among bacteria,
      antimicrobial peptides (AMPs), are receiving increased attention. Ideally, AMP
      should display high bactericidal potency, but low toxicity against (human)
      eukaryotic cells. Additionally, short and proteolytically stable AMPs are desired
      to maximize bioavailability and therapeutic versatility. METHODOLOGY AND
      PRINCIPAL FINDINGS: A facile approach is demonstrated for reaching high potency
      of ultra-short antimicrobal peptides through end-tagging with W and F stretches.
      Focusing on a peptide derived from kininogen, KNKGKKNGKH (KNK10) and truncations
      thereof, end-tagging resulted in enhanced bactericidal effect against Gram
      negative Escherichia coli and Gram-positive Staphylococcus aureus. Through end
      tagging, potency and salt resistance could be maintained down to 4-7 amino acids
      in the hydrophilic template peptide. Although tagging resulted in increased
      eukaryotic cell permeabilization at low ionic strength, the latter was
      insignificant at physiological ionic strength and in the presence of serum.
      Quantitatively, the most potent peptides investigated displayed bactericidal
      effects comparable to, or in excess of, that of the benchmark antimicrobial
      peptide LL-37. The higher bactericidal potency of the tagged peptides correlated
      to a higher degree of binding to bacteria, and resulting bacterial wall rupture.
      Analogously, tagging enhanced peptide-induced rupture of liposomes, particularly
      anionic ones. Additionally, end-tagging facilitated binding to bacterial
      lipopolysaccharide, both effects probably contributing to the selectivity
      displayed by these peptides between bacteria and eukaryotic cells. Importantly, W
      tagging resulted in peptides with maintained stability against proteolytic
      degradation by human leukocyte elastase, as well as staphylococcal aureolysin and
      V8 proteinase. The biological relevance of these findings was demonstrated ex
      vivo for pig skin infected by S. aureus and E. coli. CONCLUSIONS/SIGNIFICANCE:
      End-tagging by hydrophobic amino acid stretches may be employed to enhance
      bactericidal potency also of ultra-short AMPs at maintained limited toxicity. The
      approach is of general applicability, and facilitates straightforward synthesis
      of hydrophobically modified AMPs without the need for post-peptide synthesis
      modifications.

PMID- 19381272
TI  - Human herpesvirus replication and abnormal CD8+ T cell activation and low CD4+ T
      cell counts in antiretroviral-suppressed HIV-infected patients.
AB  - BACKGROUND: Most HIV-infected patients receiving virologically suppressive
      antiretroviral therapy continue to have abnormal, generalized T cell activation.
      We explored whether the degree of ongoing cytomegalovirus (CMV), Epstein-Barr
      virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) replication was associated
      with higher virus-specific T cell activation and the failure to achieve normal
      absolute CD4+ T cell counts in the face of long-term suppressive antiretroviral
      therapy. METHODOLOGY: Longitudinally collected PBMC and saliva specimens obtained
      from HIV-infected patients on effective antiretroviral therapy for at least one
      year (plasma HIV RNA <75 copies/mL) were examined using a multiplex CMV, EBV and
      KSHV DNA PCR assay. Eleven cases were chosen who had CD8+ T cell CD38+HLA-DR+
      expression >10% and plateau absolute CD4+ T cell counts <500 cells/microL. Five
      controls from the same study had CD8+ T cell CD38 expression <10% and plateau
      absolute CD4+ T cell counts >500 cells/microL. RESULTS AND CONCLUSIONS: Among all
      subjects combined, 18% of PMBC samples were positive for CMV DNA, and 27%, 73%
      and 24% of saliva samples were positive for CMV, EBV and KSHV DNA, respectively.
      No significant differences or trends were observed between cases and controls in
      proportions of all CMV, EBV or KSHV DNA positive specimens, proportions of
      subjects in each group that intermittently or continuously shed CMV, EBV or KSHV
      DNA in saliva, or the median number of genome copies of CMV, EBV and KSHV DNA in
      saliva. Overall, number of genome copies in saliva were lower for KSHV than for
      CMV and lower for CMV than for EBV. Although replication of CMV, EBV and KSHV
      persists in many antiretroviral-suppressed, HIV-infected patients, we observed no
      evidence in this pilot case-control study that the magnitude of such human
      herpesvirus replication is associated with abnormally increased CD8+ T cell
      activation and sub-normal plateau absolute CD4+ T cell counts following
      virologically suppressive antiretroviral therapy.

PMID- 19381273
TI  - Proteome serological determination of tumor-associated antigens in melanoma.
AB  - Proteome serology may complement expression library-based approaches as strategy
      utilizing the patients' immune responses for the identification pathogenesis
      factors and potential targets for therapy and markers for diagnosis. Melanoma is
      a relatively immunogenic tumor and antigens recognized by melanoma-specific T
      cells have been extensively studied. The specificities of antibody responses to
      this malignancy have been analyzed to some extent by molecular genetic but not
      proteomics approaches. We screened sera of 94 melanoma patients for anti-melanoma
      reactivity and detected seropositivity in two-thirds of the patients with 2-6
      antigens per case detected by 1D and an average of 2.3 per case by 2D Western
      blot analysis. For identification, antigen spots in Western blots were aligned
      with proteins in 2-DE and analyzed by mass spectrometry. 18 antigens were
      identified, 17 of which for the first time for melanoma. One of these antigens,
      galectin-3, has been related to various oncogenic processes including metastasis
      formation and invasiveness. Similarly, enolase has been found deregulated in
      different cancers. With at least 2 of 18 identified proteins implicated in
      oncogenic processes, the work confirms the potential of proteome-based antigen
      discovery to identify pathologically relevant proteins.

PMID- 19381274
TI  - Unc119 protects from Shigella infection by inhibiting the Abl family kinases.
AB  - BACKGROUND: Bacteria engage cell surface receptors and intracellular signaling
      molecules to enter the cell. Unc119 is an adaptor protein, which interacts with
      receptors and tyrosine kinases. Its role in bacterial invasion of cells is
      unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used biochemical, molecular and cell
      biology approaches to identify the binding partners of Unc119, and to study the
      effect of Unc119 on Abl family kinases and Shigella infection. We employed loss
      of-function and gain-in-function approaches to study the effect of Unc119 in a
      mouse model of pulmonary shigellosis. Unc119 interacts with Abl family kinases
      and inhibits their kinase activity. As a consequence, it inhibits Crk
      phosphorylation, which is essential for Shigella infection. Unc119 co-localizes
      with Crk and Shigella in infected cells. Shigella infectivity increases in Unc119
      deficient epithelial and macrophage cells. In a mouse model of shigellosis cell
      permeable TAT-Unc119 inhibits Shigella infection. Conversely, Unc119 knockdown in
      vivo results in enhanced bacterial invasion and increased lethality. Unc119 is an
      inducible protein. Its expression is upregulated by probacteria and bacterial
      products such as lipopolysacharide and sodium butyrate. The latter inhibits
      Shigella infection in mouse lungs but is ineffective in Unc119 deficiency.
      CONCLUSIONS: Unc119 inhibits signaling pathways that are used by Shigella to
      enter the cell. As a consequence it provides partial but significant protection
      from Shigella infections. Unc119 induction in vivo boosts host defense against
      infections.

PMID- 19381275
TI  - Uric acid is a mediator of the Plasmodium falciparum-induced inflammatory
      response.
AB  - BACKGROUND: Malaria triggers a high inflammatory response in the host that
      mediates most of the associated pathologies and contributes to death. The
      identification of pro-inflammatory molecules derived from Plasmodium is essential
      to understand the mechanisms of pathogenesis and to develop targeted
      interventions. Uric acid derived from hypoxanthine accumulated in infected
      erythrocytes has been recently proposed as a mediator of inflammation in rodent
      malaria. METHODS AND FINDINGS: We found that human erythrocytes infected with
      Plasmodium falciparum gradually accumulate hypoxanthine in their late stages of
      development. To analyze the role of hypoxanthine-derived uric acid induced by P.
      falciparum on the inflammatory cytokine response from human blood mononuclear
      cells, cultures were treated with allopurinol, to inhibit uric acid formation
      from hypoxanthine, or with uricase, to degrade uric acid. Both treatments
      significantly reduce the secretion of TNF, IL-6, IL-1beta and IL-10 from human
      cells. CONCLUSIONS AND SIGNIFICANCE: Uric acid is a major contributor of the
      inflammatory response triggered by P. falciparum in human peripheral blood
      mononuclear cells. Since the inflammatory reaction induced by P. falciparum is
      considered a major cause of malaria pathogenesis, identifying the mechanisms used
      by the parasite to induce the host inflammatory response is essential to develop
      urgently needed therapies against this disease.

PMID- 19381276
TI  - Mechanisms involved in alleviation of intestinal inflammation by bifidobacterium
      breve soluble factors.
AB  - OBJECTIVES: Soluble factors released by Bifidobacterium breve C50 (Bb) alleviate
      the secretion of pro-inflammatory cytokines by immune cells, but their effect on
      intestinal epithelium remains elusive. To decipher the mechanisms accounting for
      the cross-talk between bacteria/soluble factors and intestinal epithelium, we
      measured the capacity of the bacteria, its conditioned medium (Bb-CM) and other
      Gram(+) commensal bacteria to dampen inflammatory chemokine secretion. METHODS:
      TNFalpha-induced chemokine (CXCL8) secretion and alteration of NF-kappaB and AP-1
      signalling pathways by Bb were studied by EMSA, confocal microscopy and western
      blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS
      induced colitis in mice. RESULTS: Bb and Bb-CM, but not other commensal bacteria,
      induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial
      cells driven by both AP-1 and NF-kappaB transcription pathways and implying
      decreased phosphorylation of p38-MAPK and IkappaB-alpha molecules. In TNBS
      induced colitis in mice, Bb-CM decreased the colitis score and inflammatory
      cytokine expression, an effect reproduced by dendritic cell conditioning with Bb
      CM. CONCLUSIONS: Bb and secreted soluble factors contribute positively to
      intestinal homeostasis by attenuating chemokine production. The results indicate
      that Bb down regulate inflammation at the epithelial level by inhibiting
      phosphorylations involved in inflammatory processes and by protective
      conditioning of dendritic cells.

PMID- 19381277
TI  - Loss of the Synaptic Vesicle Protein SV2B results in reduced neurotransmission
      and altered synaptic vesicle protein expression in the retina.
AB  - The Synaptic Vesicle Protein 2 (SV2) family of transporter-like proteins is
      expressed exclusively in vesicles that undergo calcium-regulated exocytosis. Of
      the three isoforms expressed in mammals, SV2B is the most divergent. Here we
      report studies of SV2B location and function in the retina. Immunolabeling
      studies revealed that SV2B is detected in rod photoreceptor synaptic terminals
      where it is the primary isoform. In mice lacking SV2B, synaptic transmission at
      the synapse between photoreceptors and bipolar neurons was decreased, as
      evidenced by a significant reduction in the amplitude of the b-wave in
      electroretinogram recordings. Quantitative immunoblot analyses of whole eyes
      revealed that loss of SV2B was associated with reduced levels of synaptic vesicle
      proteins including synaptotagmin, VAMP, synaptophysin and the vesicular glutamate
      transporter V-GLUT1. Immunolabeling studies revealed that SV2B is detected in rod
      photoreceptor synaptic terminals where it is the primary isoform. Thus, SV2B
      contributes to the modulation of synaptic vesicle exocytosis and plays a
      significant role in regulating synaptic protein content.

PMID- 19381278
TI  - Tetrabenazine in the treatment of Huntington's disease.
AB  - Tetrabenazine (TBZ), a catecholamine-depleting agent initially developed for the
      treatment of schizophrenia, when tested for other indications, has proven to be
      more useful for the treatment of a variety of hyperkinetic movement disorders.
      These disorders include neurological diseases characterized by abnormal
      involuntary movements such as chorea associated with Huntington's disease, tics
      in Tourette's syndrome, dyskinesias and dystonias in tardive dyskinesia, also
      primary dystonias and myoclonus. This review will include and discuss studies
      published during the period of 1960-2006 regarding the clinical efficacy and
      tolerability of TBZ in Huntington's disease (HD). It will also review the
      chemistry, pharmacokinetics and dynamics of the drug and its mechanism of action
      compared to that of reserpine, the only similar compound. This review emphasizes
      the advantage of TBZ over dopamine-depleting compounds used in the treatment of
      chorea and reveals its clinical efficacy and side effects.

PMID- 19381279
TI  - Antigenic fingerprinting of H5N1 avian influenza using convalescent sera and
      monoclonal antibodies reveals potential vaccine and diagnostic targets.
AB  - BACKGROUND: Transmission of highly pathogenic avian H5N1 viruses from poultry to
      humans have raised fears of an impending influenza pandemic. Concerted efforts
      are underway to prepare effective vaccines and therapies including polyclonal or
      monoclonal antibodies against H5N1. Current efforts are hampered by the paucity
      of information on protective immune responses against avian influenza.
      Characterizing the B cell responses in convalescent individuals could help in the
      design of future vaccines and therapeutics. METHODS AND FINDINGS: To address this
      need, we generated whole-genome-fragment phage display libraries (GFPDL)
      expressing fragments of 15-350 amino acids covering all the proteins of
      A/Vietnam/1203/2004 (H5N1). These GFPDL were used to analyze neutralizing human
      monoclonal antibodies and sera of five individuals who had recovered from H5N1
      infection. This approach led to the mapping of two broadly neutralizing human
      monoclonal antibodies with conformation-dependent epitopes. In H5N1 convalescent
      sera, we have identified several potentially protective H5N1-specific human
      antibody epitopes in H5 HA[(-10)-223], neuraminidase catalytic site, and M2
      ectodomain. In addition, for the first time to our knowledge in humans, we
      identified strong reactivity against PB1-F2, a putative virulence factor,
      following H5N1 infection. Importantly, novel epitopes were identified, which were
      recognized by H5N1-convalescent sera but did not react with sera from control
      individuals (H5N1 naive, H1N1 or H3N2 seropositive). CONCLUSION: This is the
      first study, to our knowledge, describing the complete antibody repertoire
      following H5N1 infection. Collectively, these data will contribute to rational
      vaccine design and new H5N1-specific serodiagnostic surveillance tools.

PMID- 19381280
TI  - Unrecognized non-Q-wave myocardial infarction: prevalence and prognostic
      significance in patients with suspected coronary disease.
AB  - BACKGROUND: Unrecognized myocardial infarction (UMI) is known to constitute a
      substantial portion of potentially lethal coronary heart disease. However, the
      diagnosis of UMI is based on the appearance of incidental Q-waves on 12-lead
      electrocardiography. Thus, the syndrome of non-Q-wave UMI has not been
      investigated. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can
      identify MI, even when small, subendocardial, or without associated Q-waves. The
      aim of this study was to investigate the prevalence and prognosis associated with
      non-Q-wave UMI identified by DE-CMR. METHODS AND FINDINGS: We conducted a
      prospective study of 185 patients with suspected coronary disease and without
      history of clinical myocardial infarction who were scheduled for invasive
      coronary angiography. Q-wave UMI was determined by electrocardiography (Minnesota
      Code). Non-Q-wave UMI was identified by DE-CMR in the absence of
      electrocardiographic Q-waves. Patients were followed to determine the prognostic
      significance of non-Q-wave UMI. The primary endpoint was all-cause mortality. The
      prevalence of non-Q-wave UMI was 27% (50/185), compared with 8% (15/185) for Q
      wave UMI. Patients with non-Q-wave UMI were older, were more likely to have
      diabetes, and had higher Framingham risk than those without MI, but were similar
      to those with Q-wave UMI. Infarct size in non-Q-wave UMI was modest (8%+/-7% of
      left ventricular mass), and left ventricular ejection fraction (LVEF) by cine-CMR
      was usually preserved (52%+/-18%). The prevalence of non-Q-wave UMI increased
      with the extent and severity of coronary disease on angiography (p<0.0001 for
      both). Over 2.2 y (interquartile range 1.8-2.7), 16 deaths occurred: 13 in non-Q
      wave UMI patients (26%), one in Q-wave UMI (7%), and two in patients without MI
      (2%). Multivariable analysis including New York Heart Association class and LVEF
      demonstrated that non-Q-wave UMI was an independent predictor of all-cause
      mortality (hazard ratio [HR] 11.4, 95% confidence interval [CI] 2.5-51.1) and
      cardiac mortality (HR 17.4, 95% CI 2.2-137.4). CONCLUSIONS: In patients with
      suspected coronary disease, the prevalence of non-Q-wave UMI is more than 3-fold
      higher than Q-wave UMI. The presence of non-Q-wave UMI predicts subsequent
      mortality, and is incremental to LVEF. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT00493168.

PMID- 19381281
TI  - Mapping antibody epitopes of the avian H5N1 influenza virus.

PMID- 19381282
TI  - What is the significance of unrecognized non-Q-wave myocardial infarction?

PMID- 19381283
TI  - Marriage, sex, and hydrocele: an ethnographic study on the effect of filarial
      hydrocele on conjugal life and marriageability from Orissa, India.
AB  - BACKGROUND: Lymphatic filariasis (LF), a leading cause of permanent and long-term
      disability, affects 120 million people globally. Hydrocele, one of the chronic
      manifestations of LF among 27 million people worldwide, causes economic and
      psychological burdens on patients and their families. The present study explores
      and describes the impact of hydrocele on sexual and marital life as well as on
      marriageability of hydrocele patients from rural areas of Orissa, an eastern
      state of India. METHODOLOGY/PRINCIPAL FINDINGS: This paper is based on
      ethnographic data collected through focus group discussions and in-depth
      interviews with hydrocele patients, wives of hydrocele patients, and other
      participants from the community. The most worrisome effect of hydrocele for
      patients and their wives was the inability to have a satisfactory sexual life.
      The majority of patients (94%) expressed their incapacity during sexual
      intercourse, and some (87%) reported pain in the scrotum during intercourse. A
      majority of hydrocele patients' wives (94%) reported dissatisfaction in their
      sexual life. As a result of sexual dissatisfaction and physical/economic burden,
      communication has deteriorated between the couples and they are not living
      happily. This study also highlights the impact on marriageability. The wives of
      hydrocele patients said that a hydrocele patient is the "last choice" and that
      girls show reluctance to marry hydrocele patients. In some cases, the patients
      were persuaded by their wives to remove hydrocele by surgery (hydrocelectomy).
      CONCLUSIONS/SIGNIFICANCE: The objective of the morbidity management arm of the
      Global Programme to Eliminate LF should be to increase access to hydrocelectomy,
      as hydrocelectomy is the recommended intervention. Though the study area is
      covered by the programme, like in other endemic areas, hydrocelectomy has not
      been emphasised by the national LF elimination programme. The policy makers and
      programme managers should be sensitised by utilising this type of research
      finding.

PMID- 19381284
TI  - Filarial lymphedema is characterized by antigen-specific Th1 and th17
      proinflammatory responses and a lack of regulatory T cells.
AB  - BACKGROUND: Lymphatic filariasis can be associated with development of serious
      pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of
      infected patients. METHODS AND FINDINGS: To elucidate the role of CD4(+) T cell
      subsets in the development of lymphatic pathology, we examined specific sets of
      cytokines in individuals with filarial lymphedema in response to parasite antigen
      (BmA) and compared them with responses from asymptomatic infected individuals. We
      also examined expression patterns of Toll-like receptors (TLR1-10) and Nod-like
      receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly
      higher production of Th1-type cytokines-IFN-gamma and TNF-alpha-in patients with
      lymphedema compared with asymptomatic individuals. Notably, expression of the
      Th17 family of cytokines-IL-17A, IL-17F, IL-21, and IL-23-was also significantly
      upregulated by BmA stimulation in lymphedema patients. In contrast, expression of
      Foxp3, GITR, TGFbeta, and CTLA-4, known to be expressed by regulatory T cells,
      was significantly impaired in patients with lymphedema. BmA also induced
      significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in
      patients with lymphedema compared with asymptomatic controls. CONCLUSION: Our
      findings implicate increased Th1/Th17 responses and decreased regulatory T cells
      as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial
      lymphedema.

PMID- 19381285
TI  - Diagnosing schistosomiasis by detection of cell-free parasite DNA in human
      plasma.
AB  - INTRODUCTION: Schistosomiasis (bilharzia), one of the most relevant parasitoses
      of humans, is confirmed by microscopic detection of eggs in stool, urine, or
      organ biopsies. The sensitivity of these procedures is variable due to
      fluctuation of egg shedding. Serological tests on the other hand do not
      distinguish between active and past disease. In patients with acute disease
      (Katayama syndrome), both serology and direct detection may produce false
      negative results. To overcome these obstacles, we developed a novel diagnostic
      strategy, following the rationale that Schistosoma DNA may be liberated as a
      result of parasite turnover and reach the blood. Cell-free parasite DNA (CFPD)
      was detected in plasma by PCR. METHODOLOGY/PRINCIPAL FINDINGS: Real-time PCR with
      internal control was developed and optimized for detection of CFPD in human
      plasma. Distribution was studied in a mouse model for Schistosoma replication and
      elimination, as well as in human patients seen before and after treatment. CFPD
      was detectable in mouse plasma, and its concentration correlated with the course
      of anti-Schistosoma treatment. Humans with chronic disease and eggs in stool or
      urine (n = 14) showed a 100% rate of CFPD detection. CFPD was also detected in
      all (n = 8) patients with Katayama syndrome. Patients in whom no viable eggs
      could be detected and who had been treated for schistomiasis in the past (n = 30)
      showed lower detection rates (33.3%) and significantly lower CFPD concentrations.
      The duration from treatment to total elimination of CFPD from plasma was
      projected to exceed one year. CONCLUSIONS/SIGNIFICANCE: PCR for detection of CFPD
      in human plasma may provide a new laboratory tool for diagnosing schistosomiasis
      in all phases of clinical disease, including the capacity to rule out Katayama
      syndrome and active disease. Further studies are needed to confirm the clinical
      usefulness of CFPD quantification in therapy monitoring.

PMID- 19381286
TI  - A kernel for open source drug discovery in tropical diseases.
AB  - BACKGROUND: Conventional patent-based drug development incentives work badly for
      the developing world, where commercial markets are usually small to non-existent.
      For this reason, the past decade has seen extensive experimentation with
      alternative R&D institutions ranging from private-public partnerships to
      development prizes. Despite extensive discussion, however, one of the most
      promising avenues-open source drug discovery-has remained elusive. We argue that
      the stumbling block has been the absence of a critical mass of preexisting work
      that volunteers can improve through a series of granular contributions.
      Historically, open source software collaborations have almost never succeeded
      without such "kernels". METHODOLOGY/PRINCIPAL FINDINGS: HERE, WE USE A
      COMPUTATIONAL PIPELINE FOR: (i) comparative structure modeling of target
      proteins, (ii) predicting the localization of ligand binding sites on their
      surfaces, and (iii) assessing the similarity of the predicted ligands to known
      drugs. Our kernel currently contains 143 and 297 protein targets from ten
      pathogen genomes that are predicted to bind a known drug or a molecule similar to
      a known drug, respectively. The kernel provides a source of potential drug
      targets and drug candidates around which an online open source community can
      nucleate. Using NMR spectroscopy, we have experimentally tested our predictions
      for two of these targets, confirming one and invalidating the other.
      CONCLUSIONS/SIGNIFICANCE: The TDI kernel, which is being offered under the
      Creative Commons attribution share-alike license for free and unrestricted use,
      can be accessed on the World Wide Web at http://www.tropicaldisease.org. We hope
      that the kernel will facilitate collaborative efforts towards the discovery of
      new drugs against parasites that cause tropical diseases.

PMID- 19381287
TI  - Accurate real-time PCR strategy for monitoring bloodstream parasitic loads in
      chagas disease patients.
AB  - BACKGROUND: This report describes a real-time PCR (Q-PCR) strategy to quantify
      Trypanosoma cruzi (T. cruzi) DNA in peripheral blood samples from Chagas disease
      patients targeted to conserved motifs within the repetitive satellite sequence.
      METHODOLOGY/PRINCIPAL FINDINGS: The Q-PCR has a detection limit of 0.1 and 0.01
      parasites/mL, with a dynamic range of 10(6) and 10(7) for Silvio X10 cl1 (T.
      cruzi I) and Cl Brener stocks (T. cruzi IIe), respectively, an efficiency of 99%,
      and a coefficient of determination (R(2)) of 0.998. In order to express
      accurately the parasitic loads: (1) we adapted a commercial kit based on silica
      membrane technology to enable efficient processing of Guanidine Hydrochloride
      EDTA treated blood samples and minimize PCR inhibition; (2) results were
      normalized incorporating a linearized plasmid as an internal standard of the
      whole procedure; and (3) a correction factor according to the representativity of
      satellite sequences in each parasite lineage group was determined using a
      modified real-time PCR protocol (Lg-PCR). The Q-PCR strategy was applied (1) to
      estimate basal parasite loads in 43 pediatric Chagas disease patients, (2) to
      follow-up 38 of them receiving treatment with benznidazole, and (3) to monitor
      three chronic Chagas heart disease patients who underwent heart-transplantation
      and displayed events of clinical reactivation due to immunosupression.
      CONCLUSION/SIGNIFICANCE: All together, the high analytical sensitivity of the Q
      PCR strategy, the low levels of intra- and inter-assay variations, as well as the
      accuracy provided by the Lg-PCR based correction factor support this methodology
      as a key laboratory tool for monitoring clinical reactivation and etiological
      treatment outcome in Chagas disease patients.

PMID- 19381289
TI  - The Incidence of Molluscum contagiosum among American Indians and Alaska Natives.
AB  - BACKGROUND: The epidemiology of Molluscum contagiosum (MC) in the United States
      is largely unknown, despite the fact that the virus is directly communicable and
      large outbreaks occur. This study provides population-based estimates to describe
      the epidemiology of MC in the United States among American Indian and Alaska
      Native (AI/AN) persons. This population was selected because of the
      comprehensiveness and quality of available data describing utilization of out
      patient services. PRINCIPAL FINDINGS: Outpatient visits listing MC as a diagnosis
      in the Indian Health Service National Patient Information Reporting System during
      2001-2005 were analyzed to assess patient characteristics, visit frequency and
      concurrent skin conditions. Outpatient visit rates and incidence rates were
      calculated based on known population denominators (retrospective cohort). Overall
      outpatient visit rates were also calculated for the general US population using
      national data. The average annual rate of MC-associated outpatient visits was
      20.15/10,000 AI/AN persons for 2001-2005 (13,711 total visits), which was similar
      to the rate for the general US population (22.0/10,000 [95% CI: 16.9-27.1]). The
      incidence of MC-associated visits was 15.34/10,000. AI/AN children 1-4 years old
      had the highest incidence (77.12), more than twice that for children 5-14 years
      old (30.79); the incidence for infants (<1 year) was higher than that for adults.
      AI/AN persons living in the West region had the highest incidence, followed by
      those in the East and Alaska regions (26.96, 22.88 and 21.38, respectively).
      There were age-specific associations between MC and concurrent skin conditions
      (e.g., atopic dermatitis, eczema). CONCLUSIONS: This study highlights the need
      for periodic population-based measurements to assess trends in incidence and
      healthcare utilization for MC in the United States. High rates of MC were found
      among AI/AN persons, especially among children <15 years old. The AI/AN
      population would benefit from greater availability of effective strategies for
      prevention and treatment of MCV infection.

PMID- 19381288
TI  - The transcription factor NFAT5 is required for cyclin expression and cell cycle
      progression in cells exposed to hypertonic stress.
AB  - BACKGROUND: Hypertonicity can perturb cellular functions, induce DNA damage-like
      responses and inhibit proliferation. The transcription factor NFAT5 induces
      osmoprotective gene products that allow cells to adapt to sustained hypertonic
      conditions. Although it is known that NFAT5-deficient lymphocytes and renal
      medullary cells have reduced proliferative capacity and viability under
      hypertonic stress, less is understood about the contribution of this factor to
      DNA damage responses and cell cycle regulation. METHODOLOGY/PRINCIPAL FINDINGS:
      We have generated conditional knockout mice to obtain NFAT5(-/-) T lymphocytes,
      which we used as a model of proliferating cells to study NFAT5-dependent
      responses. We show that hypertonicity triggered an early, NFAT5-independent,
      genotoxic stress-like response with induction of p53, p21 and GADD45,
      downregulation of cyclins, and cell cycle arrest. This was followed by an NFAT5
      dependent adaptive phase in wild-type cells, which induced an osmoprotective gene
      expression program, downregulated stress markers, resumed cyclin expression and
      proliferation, and displayed enhanced NFAT5 transcriptional activity in S and
      G2/M. In contrast, NFAT5(-/-) cells failed to induce osmoprotective genes and
      exhibited poorer viability. Although surviving NFAT5(-/-) cells downregulated
      genotoxic stress markers, they underwent cell cycle arrest in G1/S and G2/M,
      which was associated with reduced expression of cyclins E1, A2 and B1. We also
      show that pathologic hypertonicity levels, as occurring in plasma of patients and
      animal models of osmoregulatory disorders, inhibited the induction of cyclins and
      aurora B kinase in response to T cell receptor stimulation in fresh NFAT5(-/-)
      lymphocytes. CONCLUSIONS/SIGNIFICANCE: We conclude that NFAT5 facilitates cell
      proliferation under hypertonic conditions by inducing an osmoadaptive response
      that enables cells to express fundamental regulators needed for cell cycle
      progression.

PMID- 19381290
TI  - Freeze-drying of mononuclear cells derived from umbilical cord blood followed by
      colony formation.
AB  - BACKGROUND: We recently showed that freeze-dried cells stored for 3 years at room
      temperature can direct embryonic development following cloning. However,
      viability, as evaluated by membrane integrity of the cells after freeze-drying,
      was very low; and it was mainly the DNA integrity that was preserved. In the
      present study, we improved the cells' viability and functionality after freeze
      drying. METHODOLOGY/PRINCIPAL FINDINGS: We optimized the conditions of
      directional freezing, i.e. interface velocity and cell concentration, and we
      added the antioxidant EGCG to the freezing solution. The study was performed on
      mononuclear cells (MNCs) derived from human umbilical cord blood. After freeze
      drying, we tested the viability, number of CD34(+)-presenting cells and ability
      of the rehydrated hematopoietic stem cells to differentiate into different blood
      cells in culture. The viability of the MNCs after freeze-drying and rehydration
      with pure water was 88%-91%. The total number of CD34(+)-presenting cells and the
      number of colonies did not change significantly when evaluated before freezing,
      after freeze-thawing, and after freeze-drying (5.4 x 10(4)+/-4.7, 3.49 x 10(4)+/
      6 and 6.31 x 10(4)+/-12.27 cells, respectively, and 31+/-25.15, 47+/-45.8 and
      23.44+/-13.3 colonies, respectively). CONCLUSIONS: This is the first report of
      nucleated cells which have been dried and then rehydrated with double-distilled
      water remaining viable, and of hematopoietic stem cells retaining their ability
      to differentiate into different blood cells.

PMID- 19381291
TI  - Targeting angiogenesis-dependent calcified neoplasms using combined polymer
      therapeutics.
AB  - BACKGROUND: There is an immense clinical need for novel therapeutics for the
      treatment of angiogenesis-dependent calcified neoplasms such as osteosarcomas and
      bone metastases. We developed a new therapeutic strategy to target bone
      metastases and calcified neoplasms using combined polymer-bound angiogenesis
      inhibitors. Using an advanced "living polymerization" technique, the reversible
      addition-fragmentation chain transfer (RAFT), we conjugated the
      aminobisphosphonate alendronate (ALN), and the potent anti-angiogenic agent TNP
      470 with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer through a Glycine
      Glycine-Proline-Norleucine linker, cleaved by cathepsin K, a cysteine protease
      overexpressed at resorption sites in bone tissues. In this approach, dual
      targeting is achieved. Passive accumulation is possible due to the increase in
      molecular weight following polymer conjugation of the drugs, thus extravasating
      from the tumor leaky vessels and not from normal healthy vessels. Active
      targeting to the calcified tissues is achieved by ALN's affinity to bone mineral.
      METHODS AND FINDING: The anti-angiogenic and antitumor potency of HPMA copolymer
      ALN-TNP-470 conjugate was evaluated both in vitro and in vivo. We show that free
      and conjugated ALN-TNP-470 have synergistic anti-angiogenic and antitumor
      activity by inhibiting proliferation, migration and capillary-like tube formation
      of endothelial and human osteosarcoma cells in vitro. Evaluation of anti
      angiogenic, antitumor activity and body distribution of HPMA copolymer-ALN-TNP
      470 conjugate was performed on severe combined immunodeficiency (SCID) male mice
      inoculated with mCherry-labeled MG-63-Ras human osteosarcoma and by modified
      Miles permeability assay. Our targeted bi-specific conjugate reduced VEGF-induced
      vascular hyperpermeability by 92% and remarkably inhibited osteosarcoma growth in
      mice by 96%. CONCLUSIONS: This is the first report to describe a new concept of a
      narrowly-dispersed combined polymer therapeutic designed to target both tumor and
      endothelial compartments of bone metastases and calcified neoplasms at a single
      administration. This new approach of co-delivery of two synergistic drugs may
      have clinical utility as a potential therapy for angiogenesis-dependent cancers
      such as osteosarcoma and bone metastases.

PMID- 19381292
TI  - Mapping brain response to pain in fibromyalgia patients using temporal analysis
      of FMRI.
AB  - BACKGROUND: Nociceptive stimuli may evoke brain responses longer than the
      stimulus duration often partially detected by conventional neuroimaging.
      Fibromyalgia patients typically complain of severe pain from gentle stimuli. We
      aimed to characterize brain response to painful pressure in fibromyalgia patients
      by generating activation maps adjusted for the duration of brain responses.
      METHODOLOGY/PRINCIPAL FINDINGS: Twenty-seven women (mean age: 47.8 years) were
      assessed with fMRI. The sample included nine fibromyalgia patients and nine
      healthy subjects who received 4 kg/cm(2) of pressure on the thumb. Nine
      additional control subjects received 6.8 kg/cm(2) to match the patients for the
      severity of perceived pain. Independent Component Analysis characterized the
      temporal dynamics of the actual brain response to pressure. Statistical
      parametric maps were estimated using the obtained time courses. Brain response to
      pressure (18 seconds) consistently exceeded the stimulus application (9 seconds)
      in somatosensory regions in all groups. fMRI maps following such temporal
      dynamics showed a complete pain network response (sensory-motor cortices,
      operculo-insula, cingulate cortex, and basal ganglia) to 4 kg/cm(2) of pressure
      in fibromyalgia patients. In healthy subjects, response to this low intensity
      pressure involved mainly somatosensory cortices. When matched for perceived pain
      (6.8 kg/cm(2)), control subjects showed also comprehensive activation of pain
      related regions, but fibromyalgia patients showed significantly larger activation
      in the anterior insula-basal ganglia complex and the cingulate cortex.
      CONCLUSIONS/SIGNIFICANCE: The results suggest that data-driven fMRI assessments
      may complement conventional neuroimaging for characterizing pain responses and
      that enhancement of brain activation in fibromyalgia patients may be particularly
      relevant in emotion-related regions.

PMID- 19381293
TI  - CD45RC isoform expression identifies functionally distinct T cell subsets
      differentially distributed between healthy individuals and AAV patients.
AB  - In animal models of anti-neutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis (AAV), the proportion of CD45RC T cell subsets is important for
      disease susceptibility. Their human counterparts are, however, functionally ill
      defined. In this report, we studied their distribution in healthy controls (HC),
      AAV patients and in Systemic lupus erythematous (SLE) patients as disease
      controls. We showed that CD45RC expression level on human CD4 and CD8 T cells
      identifies subsets that are highly variable among individuals. Interestingly, AAV
      patients exhibit an increased proportion of CD45RC(low) CD4 T cells as compared
      to HC and SLE patients. This increase is stable over time and independent of AAV
      subtype, ANCA specificity, disease duration, or number of relapses. We also
      analyzed the cytokine profile of purified CD4 and CD8 CD45RC T cell subsets from
      HC, after stimulation with anti-CD3 and anti-CD28 mAbs. The CD45RC subsets
      exhibit different cytokine profiles. Type-1 cytokines (IL-2, IFN-gamma and TNF
      alpha) were produced by all CD45RC T cell subsets, while the production of IL-17,
      type-2 (IL-4, IL-5) and regulatory (IL-10) cytokines was restricted to the
      CD45RC(low) subset. In conclusion, we have shown that CD45RC expression divides
      human T cells in functionally distinct subsets that are imbalanced in AAV. Since
      this imbalance is stable over time and independent of several disease parameters,
      we hypothesize that this is a pre-existing immune abnormality involved in the
      etiology of AAV.

PMID- 19381294
TI  - Phagocytosis of Staphylococcus aureus by macrophages exerts cytoprotective
      effects manifested by the upregulation of antiapoptotic factors.
AB  - It is becoming increasingly apparent that Staphylococcus aureus are able to
      survive engulfment by macrophages, and that the intracellular environment of
      these host cells, which is essential to innate host defenses against invading
      microorganisms, may in fact provide a refuge for staphylococcal survival and
      dissemination. Based on this, we postulated that S. aureus might induce
      cytoprotective mechanisms by changing gene expression profiles inside macrophages
      similar to obligate intracellular pathogens, such as Mycobacterium tuberculosis.
      To validate our hypothesis we first ascertained whether S. aureus infection could
      affect programmed cell death in human (hMDMs) and mouse (RAW 264.7) macrophages
      and, specifically, protect these cells against apoptosis. Our findings indicate
      that S. aureus-infected macrophages are more resistant to staurosporine-induced
      cell death than control cells, an effect partly mediated via the inhibition of
      cytochrome c release from mitochondria. Furthermore, transcriptome analysis of
      human monocyte-derived macrophages during S. aureus infection revealed a
      significant increase in the expression of antiapoptotic genes. This was confirmed
      by quantitative RT-PCR analysis of selected genes involved in mitochondria
      dependent cell death, clearly showing overexpression of BCL2 and MCL1.
      Cumulatively, the results of our experiments argue that S. aureus is able to
      induce a cytoprotective effect in macrophages derived from different mammal
      species, which can prevent host cell elimination, and thus allow intracellular
      bacterial survival. Ultimately, it is our contention that this process may
      contribute to the systemic dissemination of S. aureus infection.

PMID- 19381296
TI  - A fragile balance: perturbation of GABA mediated circuit in prefrontal cortex
      generates high intraindividual performance variability.
AB  - High intraindividual performance variability is one of the most robust findings
      to emerge in cognitive-experimental research of attention deficit hyperactivity
      disorder (ADHD). Evidences from studies incorporating structural or functional
      human brain mapping methods indicate that this increased intraindividual
      variability is not simply a sequel of general brain dysfunction, but is likely
      related to the functioning of neural circuits that engage the prefrontal cortex,
      particularly the dorsolateral areas (dlPFC). In order to examine further the
      anatomical and pharmacological substrate responsible for this high
      intraindividual variability disorder, we injected GABA(A) antagonist
      (bicuculline) or GABA(A) agonist (muscimol) in the dlPFC of monkeys performing a
      reflexive oculomotor task. Here we show that, whereas GABA(A) agonist injection
      induced no or minimal impairments, injection of GABA(A) antagonist dramatically
      increased the intraindividual variability of saccade response time and of saccade
      spatial accuracy (amplitude and direction). Overall, this study demonstrates that
      the balance between excitatory/inhibitory activities in the dlPFC is fragile but
      crucial, since local micro-injection of GABA(A) antagonist can induce marked
      behavioural effects. It also reveals that higher cognitive areas such as the
      dlPFC are markedly capable to influence the productions and metrics of reflexive
      movements. Altogether, this study provides promising perspectives for the
      development of new therapeutic strategies for the treatment of diseases in which
      high intravariability disorders are a prominent feature.

PMID- 19381295
TI  - Identification of novel genes and pathways regulating SREBP transcriptional
      activity.
AB  - BACKGROUND: Lipid metabolism in mammals is orchestrated by a family of
      transcription factors called sterol regulatory element-binding proteins (SREBPs)
      that control the expression of genes required for the uptake and synthesis of
      cholesterol, fatty acids, and triglycerides. SREBPs are thus essential for
      insulin-induced lipogenesis and for cellular membrane homeostasis and biogenesis.
      Although multiple players have been identified that control the expression and
      activation of SREBPs, gaps remain in our understanding of how SREBPs are
      coordinated with other physiological pathways. METHODOLOGY: To identify novel
      regulators of SREBPs, we performed a genome-wide cDNA over-expression screen to
      identify proteins that might modulate the transcription of a luciferase gene
      driven from an SREBP-specific promoter. The results were verified through
      secondary biological assays and expression data were analyzed by a novel
      application of the Gene Set Enrichment Analysis (GSEA) method.
      CONCLUSIONS/SIGNIFICANCE: We screened 10,000 different cDNAs and identified a
      number of genes and pathways that have previously not been implicated in SREBP
      control and cellular cholesterol homeostasis. These findings further our
      understanding of lipid biology and should lead to new insights into lipid
      associated disorders.

PMID- 19381298
TI  - Uncovering intrinsic modular organization of spontaneous brain activity in
      humans.
AB  - The characterization of topological architecture of complex brain networks is one
      of the most challenging issues in neuroscience. Slow (<0.1 Hz), spontaneous
      fluctuations of the blood oxygen level dependent (BOLD) signal in functional
      magnetic resonance imaging are thought to be potentially important for the
      reflection of spontaneous neuronal activity. Many studies have shown that these
      fluctuations are highly coherent within anatomically or functionally linked areas
      of the brain. However, the underlying topological mechanisms responsible for
      these coherent intrinsic or spontaneous fluctuations are still poorly understood.
      Here, we apply modern network analysis techniques to investigate how spontaneous
      neuronal activities in the human brain derived from the resting-state BOLD
      signals are topologically organized at both the temporal and spatial scales. We
      first show that the spontaneous brain functional networks have an intrinsically
      cohesive modular structure in which the connections between regions are much
      denser within modules than between them. These identified modules are found to be
      closely associated with several well known functionally interconnected subsystems
      such as the somatosensory/motor, auditory, attention, visual, subcortical, and
      the "default" system. Specifically, we demonstrate that the module-specific
      topological features can not be captured by means of computing the corresponding
      global network parameters, suggesting a unique organization within each module.
      Finally, we identify several pivotal network connectors and paths (predominantly
      associated with the association and limbic/paralimbic cortex regions) that are
      vital for the global coordination of information flow over the whole network, and
      we find that their lesions (deletions) critically affect the stability and
      robustness of the brain functional system. Together, our results demonstrate the
      highly organized modular architecture and associated topological properties in
      the temporal and spatial brain functional networks of the human brain that
      underlie spontaneous neuronal dynamics, which provides important implications for
      our understanding of how intrinsically coherent spontaneous brain activity has
      evolved into an optimal neuronal architecture to support global computation and
      information integration in the absence of specific stimuli or behaviors.

PMID- 19381299
TI  - In vitro recombination catalyzed by bacterial class 1 integron integrase IntI1
      involves cooperative binding and specific oligomeric intermediates.
AB  - Gene transfer via bacterial integrons is a major pathway for facilitating the
      spread of antibiotic resistance genes across bacteria. Recently the mechanism
      underlying the recombination catalyzed by class 1 integron recombinase (IntI1)
      between attC and attI1 was highlighted demonstrating the involvement of a single
      stranded intermediary on the attC site. However, the process allowing the
      generation of this single-stranded substrate has not been determined, nor have
      the active IntI1*DNA complexes been identified. Using the in vitro strand
      transfer assay and a crosslink strategy we previously described we demonstrated
      that the single-stranded attC sequences could be generated in the absence of
      other bacterial proteins in addition to IntI. This suggests a possible role for
      this protein in stabilizing and/or generating this structure. The mechanism of
      folding of the active IntI*DNA complexes was further analyzed and we show here
      that it involves a cooperative binding of the protein to each recombination site
      and the emergence of different oligomeric species specific for each DNA
      substrate. These findings provide further insight into the recombination reaction
      catalyzed by IntI1.

PMID- 19381297
TI  - Transgenerational stress memory is not a general response in Arabidopsis.
AB  - Adverse conditions can trigger DNA damage as well as DNA repair responses in
      plants. A variety of stress factors are known to stimulate homologous
      recombination, the most accurate repair pathway, by increasing the concentration
      of necessary enzymatic components and the frequency of events. This effect has
      been reported to last into subsequent generations not exposed to the stress. To
      establish a basis for a genetic analysis of this transgenerational stress memory,
      a broad range of treatments was tested for quantitative effects on homologous
      recombination in the progeny. Several Arabidopsis lines, transgenic for well
      established recombination traps, were exposed to 10 different physical and
      chemical stress treatments, and scored for the number of somatic homologous
      recombination (SHR) events in the treated generation as well as in the two
      subsequent generations that were not treated. These numbers were related to the
      expression level of genes involved in homologous recombination and repair. SHR
      was enhanced after the majority of treatments, confirming previous data and
      adding new effective stress types, especially interference with chromatin.
      Compounds that directly modify DNA stimulated SHR to values exceeding previously
      described induction rates, concomitant with an induction of genes involved in
      SHR. In spite of the significant stimulation in the stressed generations, the two
      subsequent non-treated generations only showed a low and stochastic increase in
      SHR that did not correlate with the degree of stimulation in the parental plants.
      Transcripts coding for SHR enzymes generally returned to pre-treatment levels in
      the progeny. Thus, transgenerational effects on SHR frequency are not a general
      response to abiotic stress in Arabidopsis and may require special conditions.

PMID- 19381300
TI  - Supplementing high-density SNP microarrays for additional coverage of disease
      related genes: addiction as a paradigm.
AB  - Commercial SNP microarrays now provide comprehensive and affordable coverage of
      the human genome. However, some diseases have biologically relevant genomic
      regions that may require additional coverage. Addiction, for example, is thought
      to be influenced by complex interactions among many relevant genes and pathways.
      We have assembled a list of 486 biologically relevant genes nominated by a panel
      of experts on addiction. We then added 424 genes that showed evidence of
      association with addiction phenotypes through mouse QTL mappings and gene co
      expression analysis. We demonstrate that there are a substantial number of SNPs
      in these genes that are not well represented by commercial SNP platforms. We
      address this problem by introducing a publicly available SNP database for
      addiction. The database is annotated using numeric prioritization scores
      indicating the extent of biological relevance. The scores incorporate a number of
      factors such as SNP/gene functional properties (including synonymy and promoter
      regions), data from mouse systems genetics and measures of human/mouse
      evolutionary conservation. We then used HapMap genotyping data to determine if a
      SNP is tagged by a commercial microarray through linkage disequilibrium. This
      combination of biological prioritization scores and LD tagging annotation will
      enable addiction researchers to supplement commercial SNP microarrays to ensure
      comprehensive coverage of biologically relevant regions.

PMID- 19381301
TI  - Chronic granulomatous disease: the European experience.
AB  - CGD is an immunodeficiency caused by deletions or mutations in genes that encode
      subunits of the leukocyte NADPH oxidase complex. Normally, assembly of the NADPH
      oxidase complex in phagosomes of certain phagocytic cells leads to a "respiratory
      burst", essential for the clearance of phagocytosed micro-organisms. CGD patients
      lack this mechanism, which leads to life-threatening infections and granuloma
      formation. However, a clear picture of the clinical course of CGD is hampered by
      its low prevalence (approximately 1:250,000). Therefore, extensive clinical data
      from 429 European patients were collected and analyzed. Of these patients 351
      were males and 78 were females. X-linked (XL) CGD (gp91(phox) deficient)
      accounted for 67% of the cases, autosomal recessive (AR) inheritance for 33%. AR
      CGD was diagnosed later in life, and the mean survival time was significantly
      better in AR patients (49.6 years) than in XL CGD (37.8 years), suggesting a
      milder disease course in AR patients. The disease manifested itself most
      frequently in the lungs (66% of patients), skin (53%), lymph nodes (50%),
      gastrointestinal tract (48%) and liver (32%). The most frequently cultured micro
      organisms per episode were Staphylococcus aureus (30%), Aspergillus spp. (26%),
      and Salmonella spp. (16%). Surprisingly, Pseudomonas spp. (2%) and Burkholderia
      cepacia (<1%) were found only sporadically. Lesions induced by inoculation with
      BCG occurred in 8% of the patients. Only 71% of the patients received antibiotic
      maintenance therapy, and 53% antifungal prophylaxis. 33% were treated with gamma
      interferon. 24 patients (6%) had received a stem cell transplantation. The most
      prominent reason of death was pneumonia and pulmonary abscess (18/84 cases),
      septicemia (16/84) and brain abscess (4/84). These data provide further insight
      in the clinical course of CGD in Europe and hopefully can help to increase
      awareness and optimize the treatment of these patients.

PMID- 19381302
TI  - How hepatitis D virus can hinder the control of hepatitis B virus.
AB  - BACKGROUND: Hepatitis D (or hepatitis delta) virus is a defective virus that
      relies on hepatitis B virus (HBV) for transmission; infection with hepatitis D
      can occur only as coinfection with HBV or superinfection of an existing HBV
      infection. Because of the bond between the two viruses, control measures for HBV
      may have also affected the spread of hepatitis D, as evidenced by the decline of
      hepatitis D in recent years. Since the presence of hepatitis D is associated with
      suppressed HBV replication and possibly infectivity, it is reasonable to
      speculate that hepatitis D may facilitate the control of HBV. METHODOLOGY AND
      PRINCIPAL FINDINGS: We introduced a mathematical model for the transmission of
      HBV and hepatitis D, where individuals with dual HBV and hepatitis D infection
      transmit both viruses. We calculated the reproduction numbers of single HBV
      infections and dual HBV and hepatitis D infections and examined the endemic
      prevalences of the two viruses. The results show that hepatitis D virus modulates
      not only the severity of the HBV epidemic, but also the impact of interventions
      for HBV. Surprisingly we find that the presence of hepatitis D virus may hamper
      the eradication of HBV. Interventions that aim to reduce the basic reproduction
      number of HBV below one may not be sufficient to eradicate the virus, as control
      of HBV depends also on the reproduction numbers of dual infections. CONCLUSIONS
      AND SIGNIFICANCE: For populations where hepatitis D is endemic, plans for control
      programs ignoring the presence of hepatitis D may underestimate the HBV epidemic
      and produce overoptimistic results. The current HBV surveillance should be
      augmented with monitoring of hepatitis D, in order to improve accuracy of the
      monitoring and the efficacy of control measures.

PMID- 19381303
TI  - Persistent hyperdopaminergia decreases the peak frequency of hippocampal theta
      oscillations during quiet waking and REM sleep.
AB  - Long-term changes in dopaminergic signaling are thought to underlie the
      pathophysiology of a number of psychiatric disorders. Several conditions are
      associated with cognitive deficits such as disturbances in attention processes
      and learning and memory, suggesting that persistent changes in dopaminergic
      signaling may alter neural mechanisms underlying these processes. Dopamine
      transporter knockout (DAT-KO) mice exhibit a persistent five-fold increase in
      extracellular dopamine levels. Here, we demonstrate that DAT-KO mice display
      lower hippocampal theta oscillation frequencies during baseline periods of waking
      and rapid-eye movement sleep. These altered theta oscillations are not reversed
      via treatment with the antidopaminergic agent haloperidol. Thus, we propose that
      persistent hyperdopaminergia, together with secondary alterations in other
      neuromodulatory systems, results in lower frequency activity in neural systems
      responsible for various cognitive processes.

PMID- 19381304
TI  - NMDA receptor stimulation induces reversible fission of the neuronal endoplasmic
      reticulum.
AB  - With few exceptions the endoplasmic reticulum (ER) is considered a continuous
      system of endomembranes within which proteins and ions can move. We have studied
      dynamic structural changes of the ER in hippocampal neurons in primary culture
      and organotypic slices. Fluorescence recovery after photobleaching (FRAP) was
      used to quantify and model ER structural dynamics. Ultrastructure was assessed by
      electron microscopy. In live cell imaging experiments we found that, under basal
      conditions, the ER of neuronal soma and dendrites was continuous. The smooth and
      uninterrupted appearance of the ER changed dramatically after glutamate
      stimulation. The ER fragmented into isolated vesicles in a rapid fission reaction
      that occurred prior to overt signs of neuronal damage. ER fission was found to be
      independent of ER calcium levels. Apart from glutamate, the calcium ionophore
      ionomycin was able to induce ER fission. The N-methyl, D-aspartate (NMDA)
      receptor antagonist MK-801 inhibited ER fission induced by glutamate as well as
      by ionomycin. Fission was not blocked by either ifenprodil or kinase inhibitors.
      Interestingly, sub-lethal NMDA receptor stimulation caused rapid ER fission
      followed by fusion. Hence, ER fission is not strictly associated with cellular
      damage or death. Our results thus demonstrate that neuronal ER structure is
      dynamically regulated with important consequences for protein mobility and ER
      luminal calcium tunneling.

PMID- 19381305
TI  - Function of retinoic acid receptors during embryonic development.
AB  - Retinoids, the active metabolites of vitamin A, regulate complex gene networks
      involved in vertebrate morphogenesis, growth, cellular differentiation and
      homeostasis. Studies performed in vitro, using either acellular systems or
      transfected cells, have shown that retinoid actions are mediated through
      heterodimers between the RAR and RXR nuclear receptors. However, in vitro studies
      indicate what is possible, but not necessarily what is actually occurring in
      vivo, because they are performed under non-physiological conditions. Therefore,
      genetic approaches in the animal have been be used to determine the physiological
      functions of retinoid receptors. Homologous recombination in embryonic stem cells
      has been used to generate germline null mutations of the RAR- and RXR-coding
      genes in the mouse. As reviewed here, the generation of such germline mutations,
      combined with pharmacological approaches to block the RA signalling pathway, has
      provided genetic evidence that RAR/RXR heterodimers are indeed the functional
      units transducing the RA signal during prenatal development. However, due to (i)
      the complexity in "hormonal" signalling through transduction by the multiple RARs
      and RXRs, (ii) the functional redundancies (possibly artefactually generated by
      the mutations) within receptor isotypes belonging to a given family, and (iii) in
      utero or early postnatal lethality of certain germline null mutations, these
      genetic studies have failed to reveal all the physiological functions of RARs and
      RXRs, notably in adults. Spatio-temporally-controlled somatic mutations generated
      in given cell types/tissues and at chosen times during postnatal life, will be
      required to reveal all the functions of RAR and RXR throughout the lifetime of
      the mouse.

PMID- 19381307
TI  - Catch-up growth following fetal growth restriction promotes rapid restoration of
      fat mass but without metabolic consequences at one year of age.
AB  - BACKGROUND: Fetal growth restriction (FGR) followed by rapid weight gain during
      early life has been suggested to be the initial sequence promoting central
      adiposity and insulin resistance. However, the link between fetal and early
      postnatal growth and the associated anthropometric and metabolic changes have
      been poorly studied. METHODOLOGY/PRINCIPAL FINDINGS: Over the first year of post
      natal life, changes in body mass index, skinfold thickness and hormonal
      concentrations were prospectively monitored in 94 infants in whom the fetal
      growth velocity had previously been measured using a repeated standardized
      procedure of ultrasound fetal measurements. 45 infants, thinner at birth, had
      experienced previous FGR (FGR+) regardless of birth weight. Growth pattern in the
      first four months of life was characterized by greater change in BMI z-score in
      FGR+ (+1.26+/-1.2 vs +0.58 +/-1.17 SD in FGR-) resulting in the restoration of
      BMI and of fat mass to values similar to FGR-, independently of caloric intakes.
      Growth velocity after 4 months was similar and BMI z-score and fat mass remained
      similar at 12 months of age. At both time-points, fetal growth velocity was an
      independent predictor of fat mass in FGR+. At one year, fasting insulin levels
      were not different but leptin was significantly higher in the FGR+ (4.43+/-1.41
      vs 2.63+/-1 ng/ml in FGR-). CONCLUSION: Early catch-up growth is related to the
      fetal growth pattern itself, irrespective of birth weight, and is associated with
      higher insulin sensitivity and lower leptin levels after birth. Catch-up growth
      promotes the restoration of body size and fat stores without detrimental
      consequences at one year of age on body composition or metabolic profile. The
      higher leptin concentration at one year may reflect a positive energy balance in
      children who previously faced fetal growth restriction.

PMID- 19381308
TI  - Linking joint commission inpatient core measures and national patient safety
      goals with evidence.
AB  - As an initiative of Baylor Health Care System's Best Care Committee, we
      summarized the association between the Joint Commission's hospital core
      measures/safety goals and patient outcomes. This summary (which will be formatted
      as a small, laminated card) can be used by change leaders to communicate the
      relevance of clinical quality goals. By disseminating this evidence broadly, we
      aim to further invest clinical staff in delivery of specific care processes,
      maximize care efforts related to core measures, and extend quality improvement
      efforts within our organization.

PMID- 19381309
TI  - Financial performance of primary care physician practices prior to electronic
      health record implementation.
AB  - While electronic health records (EHRs) are being widely implemented across the
      nation, few empirical data are currently available regarding their potential
      impact on financial performance and resource use. HealthTexas Provider Network is
      implementing a networkwide EHR, providing a unique opportunity to describe and
      evaluate fiscal effects. We conducted a retrospective, longitudinal observational
      study of financial performance related to inputs and income- and productivity
      related outputs for the 33 primary care practices (July 2002-April 2006). Models
      for each outcome were constructed to test for a linear trend over time, adjusted
      for practice characteristics. F tests based on these models were used to
      determine the effect of each adjustor and to determine existence of a trend in
      each outcome. The observed staff per physician full-time equivalent (FTE) (3.6)
      was similar to staffing ratios reported for other primary care-only practices,
      while observation of 4692 work relative value units per physician FTE annually
      was higher than reported nationally. Significant monthly trends were identified
      for three of the outcome measures. During the pre-EHR baseline period, staffing
      ratios were equivalent to and physician productivity greater than reports
      available for these measures nationally or in other settings. Identification of
      time trends in three measures will allow these to be accounted for in the model
      used to evaluate the financial performance impact of EHR implementation.

PMID- 19381310
TI  - Minimizing patient exposure to ionizing radiation from computed tomography scans.

PMID- 19381311
TI  - Predictive factors for early postoperative hypocalcemia after surgery for primary
      hyperparathyroidism.
AB  - The purpose of this study was to identify patients at risk for hypocalcemia after
      parathyroid surgery. The charts of 99 patients who underwent parathyroid surgery
      over a 2-year period using a rapid intraoperative parathyroid hormone (IOPTH)
      assay were retrospectively reviewed. Data for patient demographics, preoperative
      parathyroid hormone and calcium levels, IOPTH levels, and postoperative calcium
      levels were reviewed, and trends were analyzed for patients who had postoperative
      hypocalcemia. Of the 99 patients, 91 had one gland excised and 8 had two glands
      excised. Preoperative calcium levels ranged from 8.9 to 15.6 mg/dL. Sixty-seven
      of the patients had a >50% drop in IOPTH at 5 minutes, and 82 had a >50% drop in
      IOPTH by 10 minutes. Twelve patients had early hypocalcemia. Parathyroid weight
      and surgery type were not significant factors in predicting postoperative
      hypocalcemia. A drop of >80% in IOPTH at 10 minutes was a significant factor for
      postoperative hypocalcemia (P = 0.02). In addition, having normal or only
      minimally elevated preoperative calcium was an independent risk factor for
      postoperative hypocalcemia (P = 0.05). Our study has shown that postoperative
      calcium supplementation and in-hospital monitoring should be considered in
      patients with a preoperative calcium level in the normal range and with an IOPTH
      that has dropped by >80%.

PMID- 19381313
TI  - Invited commentary.

PMID- 19381312
TI  - Prevention of meconium aspiration syndrome: an update and the Baylor experience.
AB  - The approach to preventing meconium aspiration syndrome (MAS) in the newborn has
      changed markedly over the last 30 years. In the late 1970s, all infants born
      through meconium-stained amniotic fluid (MSAf) had upper-airway suctioning before
      delivery of the shoulders and then had tracheal intubation and suctioning in the
      delivery room. Now suctioning of the upper airway is no longer recommended, and
      only "depressed" infants are intubated for tracheal suctioning. The incidence of
      MAS and the associated high mortality rate have both declined significantly over
      time. This is due to improved antepartum and intrapartum obstetrical management
      as well as the postdelivery resuscitation of the neonate born through MSAf. MAS
      is no longer considered to be solely a postnatal disorder that is preventable
      with routine delivery room suctioning of the trachea; rather, it is considered a
      complex and multifactorial disorder with antenatal as well as intrapartum
      factors. The incidence and severity of MAS have been positively affected by a
      combined obstetrical and neonatal approach to the infant born through MSAf. In
      this article, we detail our experience at Baylor University Medical Center with
      MAS and its prevention and review the current literature.

PMID- 19381306
TI  - Retinoid-related orphan receptors (RORs): critical roles in development,
      immunity, circadian rhythm, and cellular metabolism.
AB  - The last few years have witnessed a rapid increase in our knowledge of the
      retinoid-related orphan receptors RORalpha, -beta, and -gamma (NR1F1-3), their
      mechanism of action, physiological functions, and their potential role in several
      pathologies. The characterization of ROR-deficient mice and gene expression
      profiling in particular have provided great insights into the critical functions
      of RORs in the regulation of a variety of physiological processes. These studies
      revealed that RORalpha plays a critical role in the development of the
      cerebellum, that both RORalpha and RORbeta are required for the maturation of
      photoreceptors in the retina, and that RORgamma is essential for the development
      of several secondary lymphoid tissues, including lymph nodes. RORs have been
      further implicated in the regulation of various metabolic pathways, energy
      homeostasis, and thymopoiesis. Recent studies identified a critical role for
      RORgamma in lineage specification of uncommitted CD4+ T helper cells into Th17
      cells. In addition, RORs regulate the expression of several components of the
      circadian clock and may play a role in integrating the circadian clock and the
      rhythmic pattern of expression of downstream (metabolic) genes. Study of ROR
      target genes has provided insights into the mechanisms by which RORs control
      these processes. Moreover, several reports have presented evidence for a
      potential role of RORs in several pathologies, including osteoporosis, several
      autoimmune diseases, asthma, cancer, and obesity, and raised the possibility that
      RORs may serve as potential targets for chemotherapeutic intervention. This
      prospect was strengthened by recent evidence showing that RORs can function as
      ligand-dependent transcription factors.

PMID- 19381314
TI  - Use of instructional video to prepare parents for learning infant cardiopulmonary
      resuscitation.
AB  - Parents of premature infants often receive infant cardiopulmonary resuscitation
      (CPR) training prior to discharge from the hospital, but one study showed that
      27.5% of parents could not demonstrate adequate CPR skills after completing an
      instructor-led class. We hypothesized that parents who viewed an instructional
      video on infant CPR before attending the class would perform better on a
      standardized skills test than parents who attended the class with no preparation.
      Parents randomized to the intervention (video) group viewed the video within 48
      hours of the CPR class. Parents in the control group attended the class with no
      special preparation. All parents completed the CPR skills checklist test, usually
      within 7 days after class and before the infant's hospital discharge. The test
      rated subjects' skills in the areas of assessment, ventilation, and chest
      compressions; each section was rated as good, fair, or fail. In this pass/fail
      test, students had to be rated good or fair on all three sections to pass. All 10
      subjects in the video group passed the test versus only 9 of 13 in the control
      group, but this difference was not significant (P = 0.08). However, 8 of 10 (80%)
      subjects in the video group were rated as good on all three sections, versus only
      3 of 13 (18.7%) in the control group, and this was a significant difference (P =
      0.012). We conclude that preparation of students using an instructional video
      prior to infant CPR class is associated with improvement in skills performance as
      measured by a standardized skills test. Video preparation is relatively
      inexpensive, eliminates the barrier of reading ability for preparation, and can
      be done at the convenience of the parent.

PMID- 19381317
TI  - Endovascular treatment of an aberrant right subclavian artery aneurysm with use
      of the Zenith iliac plug.
AB  - Aberrant right subclavian artery aneurysms are rare but demonstrate a propensity
      toward rupture; thus, early elective repair is mandated. Novel endovascular
      modalities are available to offer less-invasive treatment for a patient
      population with increasing comorbidities. We report a case of a 65-year-old woman
      with an aberrant right subclavian artery aneurysm causing dysphagia lusoria. The
      aneurysm was excluded proximally at Kommerell's diverticulum with a Zenith iliac
      plug and excluded distally by surgical ligation combined with a right carotid
      subclavian artery bypass to preserve extremity perfusion.

PMID- 19381316
TI  - Ciguatera poisoning: an unwelcome vacation experience.

PMID- 19381318
TI  - A patient reflects on chronic illness-and support from family and physicians.
AB  - Note: This editorial was a college essay; the assignment was to write an
      acceptance speech for an award given for something the student had accomplished.
      Tim Prevou has been treated since age 6 by Dr. Virginia Pascual, a pediatric
      rheumatologist and researcher at Baylor Research Institute. Dr. Pascual
      collaborated with Dr. Carol Wise, who found the mutated gene responsible for PAPA
      syndrome; she and her team later found that IL-1 blockade was an effective
      therapy. Dr. Pascual commented: "This therapy completely cured Tim's twin
      brothers and completely resolved Tim's arthritis. Tim's severe pyoderma lesions
      took more effort, but eventually we also got them under control. ... He is the
      only patient over 18 years old that I still see in the clinic. ... I am very
      proud of him."

PMID- 19381319
TI  - A suggestion for the stimulus.

PMID- 19381315
TI  - Acupuncture as a complementary therapy in chemotherapy-induced nausea and
      vomiting.
AB  - The effect of acupuncture on chemotherapy-induced nausea and vomiting has been
      studied over the past 20 years, and clinical evidence gathered to date has been
      favorable. Current practice guidelines recommend acupuncture as a complementary
      therapy for uncontrolled nausea and vomiting induced by chemotherapy.
      Nevertheless, a placebo effect may have been present in studies that had no
      control group, and unanswered questions remain-particularly since newer and more
      effective antiemetic medications have become available. A research study
      employing adjunctive electroacupuncture for both acute and delayed chemotherapy
      induced nausea and vomiting is proposed to address some of the unanswered
      questions.

PMID- 19381320
TI  - Mass in the neck after radiation exposure from Chernobyl disaster.

PMID- 19381321
TI  - Pustules and dystrophy of the nails.

PMID- 19381322
TI  - Abdominal pain, nausea, and vomiting in a 10-year-old girl.

PMID- 19381323
TI  - Wide-QRS tachycardia immediately after aortic valve replacement.

PMID- 19381325
TI  - Who is an expert? A quick primer on an evasive concept.

PMID- 19381326
TI  - Facts and ideas from anywhere.

PMID- 19381327
TI  - Hitting and missing targets by ambulance services for emergency calls: effects of
      different systems of performance measurement within the UK.
AB  - Following devolution, differences developed between UK countries in systems of
      measuring performance against a common target that ambulance services ought to
      respond to 75% of calls for what may be immediately life threatening emergencies
      (category A calls) within 8 minutes. Only in England was this target integral to
      a ranking system of 'star rating', which inflicted reputational damage on
      services that failed to hit targets, and only in England has this target been
      met. In other countries, the target has been missed by such large margins that
      services would have been publicly reported as failing, if they had been covered
      by the English system of star ratings. The paper argues that this case-study adds
      to evidence from comparisons of different systems of hospital performance
      measurement that, to have an effect, these systems need to be designed to inflict
      reputational damage on those that have performed poorly; and it explores
      implications of this hypothesis. The paper also asks questions about the adequacy
      of systems of performance measurement of ambulance services in UK countries.

PMID- 19381328
TI  - Bias modelling in evidence synthesis.
AB  - Policy decisions often require synthesis of evidence from multiple sources, and
      the source studies typically vary in rigour and in relevance to the target
      question. We present simple methods of allowing for differences in rigour (or
      lack of internal bias) and relevance (or lack of external bias) in evidence
      synthesis. The methods are developed in the context of reanalysing a UK National
      Institute for Clinical Excellence technology appraisal in antenatal care, which
      includes eight comparative studies. Many were historically controlled, only one
      was a randomized trial and doses, populations and outcomes varied between studies
      and differed from the target UK setting. Using elicited opinion, we construct
      prior distributions to represent the biases in each study and perform a bias
      adjusted meta-analysis. Adjustment had the effect of shifting the combined
      estimate away from the null by approximately 10%, and the variance of the
      combined estimate was almost tripled. Our generic bias modelling approach allows
      decisions to be based on all available evidence, with less rigorous or less
      relevant studies downweighted by using computationally simple methods.

PMID- 19381329
TI  - Accounting for uncertainty in health economic decision models by using model
      averaging.
AB  - Health economic decision models are subject to considerable uncertainty, much of
      which arises from choices between several plausible model structures, e.g.
      choices of covariates in a regression model. Such structural uncertainty is
      rarely accounted for formally in decision models but can be addressed by model
      averaging. We discuss the most common methods of averaging models and the
      principles underlying them. We apply them to a comparison of two surgical
      techniques for repairing abdominal aortic aneurysms. In model averaging,
      competing models are usually either weighted by using an asymptotically
      consistent model assessment criterion, such as the Bayesian information
      criterion, or a measure of predictive ability, such as Akaike's information
      criterion. We argue that the predictive approach is more suitable when modelling
      the complex underlying processes of interest in health economics, such as
      individual disease progression and response to treatment.

PMID- 19381330
TI  - A re-evaluation of random-effects meta-analysis.
AB  - Meta-analysis in the presence of unexplained heterogeneity is frequently
      undertaken by using a random-effects model, in which the effects underlying
      different studies are assumed to be drawn from a normal distribution. Here we
      discuss the justification and interpretation of such models, by addressing in
      turn the aims of estimation, prediction and hypothesis testing. A particular
      issue that we consider is the distinction between inference on the mean of the
      random-effects distribution and inference on the whole distribution. We suggest
      that random-effects meta-analyses as currently conducted often fail to provide
      the key results, and we investigate the extent to which distribution-free,
      classical and Bayesian approaches can provide satisfactory methods. We conclude
      that the Bayesian approach has the advantage of naturally allowing for full
      uncertainty, especially for prediction. However, it is not without problems,
      including computational intensity and sensitivity to a priori judgements. We
      propose a simple prediction interval for classical meta-analysis and offer
      extensions to standard practice of Bayesian meta-analysis, making use of an
      example of studies of 'set shifting' ability in people with eating disorders.

PMID- 19381331
TI  - High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma
      patients.
AB  - BACKGROUND: Metastatic melanoma is an untreatable cancer lacking reliable and non
      invasive markers of disease progression. Exosomes are small vesicles secreted by
      normal as well as tumor cells. Human tumor-derived exosomes are involved in
      malignant progression and we evaluated the presence of exosomes in plasma of
      melanoma patients as a potential tool for cancer screening and follow-up.
      METHODOLOGY/PRINCIPAL FINDINGS: We designed an in-house sandwich ELISA (Exotest)
      to capture and quantify exosomes in plasma based on expression of housekeeping
      proteins (CD63 and Rab-5b) and a tumor-associated marker (caveolin-1). Western
      blot and flow cytometry analysis of exosomes were used to confirm the Exotest
      based findings. The Exotest allowed sensitive detection and quantification of
      exosomes purified from human tumor cell culture supernatants and plasma from SCID
      mice engrafted with human melanoma. Plasma levels of exosomes in melanoma
      engrafted SCID mice correlated to tumor size. We evaluated the levels of plasma
      exosomes expressing CD63 and caveolin-1 in melanoma patients (n = 90) and healthy
      donors (n = 58). Consistently, plasma exosomes expressing CD63 (504+/-315) or
      caveolin-1 (619+/-310) were significantly increased in melanoma patients as
      compared to healthy donors (223+/-125 and 228+/-102, respectively). While the
      Exotest for CD63+ plasma exosomes had limited sensitivity (43%) the Exotest for
      detection of caveolin-1+ plasma exosomes showed a higher sensitivity (68%).
      Moreover, caveolin-1+ plasma exosomes were significantly increased with respect
      to CD63+ exosomes in the patients group. CONCLUSIONS/SIGNIFICANCE: We describe a
      new non-invasive assay allowing detection and quantification of human exosomes in
      plasma of melanoma patients. Our results suggest that the Exotest for detection
      of plasma exosomes carrying tumor-associated antigens may represent a novel tool
      for clinical management of cancer patients.

PMID- 19381332
TI  - Comparison of a flow assay for brucellosis antibodies with the reference cELISA
      test in West African Bos indicus.
AB  - Brucellosis is considered by the Food and Agricultural Organisation and the World
      Health Organisation as one of the most widespread zoonoses in the world. It is a
      major veterinary public health challenge as animals are almost exclusively the
      source of infection for people. It is often undiagnosed in both human patients
      and the animal sources and it is widely acknowledged that the epidemiology of
      brucellosis in humans and animals is poorly understood, particularly in sub
      Saharan Africa. It is therefore important to develop better diagnostic tools in
      order to improve our understanding of the epidemiology and also for use in the
      field for disease control and eradication. As with any new diagnostic test, it is
      essential that it is validated in as many populations as possible in order to
      characterise its performance and improve the interpretation of its results. This
      paper describes a comparison between a new lateral flow assasy (LFA) for bovine
      brucellosis and the widely used cELISA in a no gold standard analysis to estimate
      test performance in this West African cattle population. A Bayesian formulation
      of the Hui-Walter latent class model incorporated previous studies' data on
      sensitivity and specificity of the cELISA. The results indicate that the new LFA
      is very sensitive (approximately 87%) and highly specific (approximately 97%).
      The analysis also suggests that the current cut-off of the cELSIA may not be
      optimal for this cattle population but alternative cut-offs did not significantly
      change the estimates of the LFA. This study demonstrates the potential usefulness
      of this simple to use test in field based surveillance and control which could be
      easily adopted for use in developing countries with only basic laboratory
      facilities.

PMID- 19381333
TI  - The effect of high glucocorticoid administration and food restriction on rodent
      skeletal muscle mitochondrial function and protein metabolism.
AB  - BACKGROUND: Glucocorticoids levels are high in catabolic conditions but it is
      unclear how much of the catabolic effects are due to negative energy balance
      versus glucocorticoids and whether there are distinct effects on metabolism and
      functions of specific muscle proteins. METHODOLOGY/PRINCIPAL FINDINGS: We
      determined whether 14 days of high dose methylprednisolone (MPred, 4 mg/kg/d) Vs
      food restriction (FR, food intake matched to MPred) in rats had different effects
      on muscle mitochondrial function and protein fractional synthesis rates (FSR).
      Lower weight loss (15%) occurred in FR than in MPred (30%) rats, while a 15%
      increase occurred saline-treated Controls. The per cent muscle loss was
      significantly greater for MPred than FR. Mitochondrial protein FSR in MPred rats
      was lower in soleus (51 and 43%, respectively) and plantaris (25 and 55%) than in
      FR, while similar decline in protein FSR of the mixed, sarcoplasmic, and myosin
      heavy chain occurred. Mitochondrial enzymatic activity and ATP production were
      unchanged in soleus while in plantaris cytochrome c oxidase activity was lower in
      FR than Control, and ATP production rate with pyruvate + malate in MPred
      plantaris was 28% lower in MPred. Branched-chain amino acid catabolic enzyme
      activities were higher in both FR and MPred rats indicating enhanced amino acid
      oxidation capacity. CONCLUSION/SIGNIFICANCE: MPred and FR had little impact on
      mitochondrial function but reduction in muscle protein synthesis occurred in
      MPred that could be explained on the basis of reduced food intake. A greater
      decline in proteolysis may explain lesser muscle loss in FR than in MPred rats.

PMID- 19381334
TI  - The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation.
AB  - Translation fidelity is critical for protein synthesis and to ensure correct cell
      functioning. Mutations in the protein synthesis machinery or environmental
      factors that increase synthesis of mistranslated proteins result in cell death
      and degeneration and are associated with neurodegenerative diseases, cancer and
      with an increasing number of mitochondrial disorders. Remarkably, mRNA
      mistranslation plays critical roles in the evolution of the genetic code, can be
      beneficial under stress conditions in yeast and in Escherichia coli and is an
      important source of peptides for MHC class I complex in dendritic cells. Despite
      this, its biology has been overlooked over the years due to technical
      difficulties in its detection and quantification. In order to shed new light on
      the biological relevance of mistranslation we have generated codon misreading in
      Saccharomyces cerevisiae using drugs and tRNA engineering methodologies.
      Surprisingly, such mistranslation up-regulated the longevity gene PNC1. Similar
      results were also obtained in cells grown in the presence of amino acid analogues
      that promote protein misfolding. The overall data showed that PNC1 is a biomarker
      of mRNA mistranslation and protein misfolding and that PNC1-GFP fusions can be
      used to monitor these two important biological phenomena in vivo in an easy
      manner, thus opening new avenues to understand their biological relevance.

PMID- 19381336
TI  - Unexpected Hepatotoxicity of Rifampin and Saquinavir/Ritonavir in Healthy Male
      Volunteers.
AB  - OBJECTIVES: Rifampin is a potent inducer of the cytochrome P450 3A4 isoenzyme
      (CYP3A4) that metabolizes most protease inhibitor (PI) antiretrovirals. This
      study was designed to evaluate the steady-state pharmacokinetics and tolerability
      of the coadministration of the PIs saquinavir and ritonavir (a CYP3A4 inhibitor
      used as a pharmacoenhancer of other PIs) and rifampin when coadministered in
      healthy HIV-negative volunteers. METHODS: In an open-label, randomized, one
      sequence, two-period crossover study involving 28 healthy HIV-negative
      volunteers, arm 1 was randomized to receive saquinavir/ritonavir 1000/100 mg
      twice daily while arm 2 received rifampin 600 mg once daily for 14 days. Both
      arms were then to receive concomitant saquinavir/ritonavir and rifampin for 2
      additional weeks. Vital signs, electrocardiography, laboratory analyses, and
      blood levels of total saquinavir, ritonavir, rifampin, and desacetyl-rifampin,
      the primary metabolite of rifampin, were measured. RESULTS: In arm 1, 10/14 (71%)
      and, in arm 2, 11/14 (79%) participants completed the first study phase; eight
      participants in arm 1 and nine in arm 2 went on to receive both
      saquinavir/ritonavir and rifampin. Following substantial elevations (>/= grade 2)
      in hepatic transaminases in participants receiving the coadministered agents, the
      study was discontinued prematurely. Two participants in arm 1 displayed moderate
      elevations after five and four doses of rifampin, respectively. In arm 2, all
      participants experienced severe elevations within 4 days of initiating
      saquinavir/ritonavir. Clinical symptoms (e.g., nausea, vomiting, abdominal pain,
      and headache) were more common and severe in arm 2. Clinical symptoms abated and
      transaminases normalized following drug discontinuation. Limited pharmacokinetic
      data suggest a possible relationship between transaminase elevation and elevated
      rifampin and desacetyl-rifampin concentrations. CONCLUSIONS: Although not
      confirmed in HIV-infected patients, the data indicate that rifampin should not be
      coadministered with saquinavir/ritonavir.

PMID- 19381335
TI  - FRAP analysis on red alga reveals the fluorescence recovery is ascribed to
      intrinsic photoprocesses of phycobilisomes than large-scale diffusion.
AB  - BACKGROUND: Phycobilisomes (PBsomes) are the extrinsic antenna complexes upon the
      photosynthetic membranes in red algae and most cyanobacteria. The PBsomes in the
      cyanobacteria has been proposed to present high lateral mobility on the thylakoid
      membrane surface. In contrast, direct measurement of PBsome motility in red algae
      has been lacking so far. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we
      investigated the dynamics of PBsomes in the unicellular red alga Porphyridium
      cruentum in vivo and in vitro, using fluorescence recovery after photobleaching
      (FRAP). We found that part of the fluorescence recovery could be detected in both
      partially- and wholly-bleached wild-type and mutant F11 (UTEX 637) cells. Such
      partial fluorescence recovery was also observed in glutaraldehyde-treated and
      betaine-treated cells in which PBsome diffusion should be restricted by cross
      linking effect, as well as in isolated PBsomes immobilized on the glass slide.
      CONCLUSIONS/SIGNIFICANCE: On the basis of our previous structural results showing
      the PBsome crowding on the native photosynthetic membrane as well as the present
      FRAP data, we concluded that the fluorescence recovery observed during FRAP
      experiment in red algae is mainly ascribed to the intrinsic photoprocesses of the
      bleached PBsomes in situ, rather than the rapid diffusion of PBsomes on thylakoid
      membranes in vivo. Furthermore, direct observations of the fluorescence dynamics
      of phycoerythrins using FRAP demonstrated the energetic decoupling of
      phycoerythrins in PBsomes against strong excitation light in vivo, which is
      proposed as a photoprotective mechanism in red algae attributed by the PBsomes in
      response to excess light energy.

PMID- 19381337
TI  - Potential Hepatotoxicity of Efavirenz and Saquinavir/Ritonavir Coadministration
      in Healthy Volunteers.
AB  - OBJECTIVE: This study was designed to investigate the pharmacokinetic effects of
      coadministration of saquinavir/ritonavir with efavirenz at steady state. METHODS:
      Healthy volunteers in this open-label, two-arm, one-sequence, two-period
      crossover study (planned enrollment of 40 participants) were randomized to one of
      two treatment arms: those in Arm 1 were scheduled to receive saquinavir/ritonavir
      1,000/100 mg orally twice daily for 29 days and efavirenz 600 mg orally once
      daily starting on day 15 and continuing through day 29; participants randomized
      to Arm 2 were to receive efavirenz once daily for 29 days and
      saquinavir/ritonavir 1,000/100 mg twice daily starting on day 15 through day 29.
      Assessments included vital signs, laboratory analyses, electrocardiography, and
      blood levels of total saquinavir, ritonavir, and efavirenz. Pharmacokinetic
      parameters included C(max) (maximum observed plasma concentration), t(max) (time
      to reach the maximum observed plasma concentration), (apparent elimination half
      life), and AUC(0-tau) (area-under-the-plasma-concentration-time curve over one
      dosing interval). RESULTS: Eight participants (four in each arm) were enrolled;
      only two (one from each treatment arm) reached day 15 of the study and received
      the concurrent initial doses of saquinavir/ritonavir and efavirenz. The study was
      terminated prematurely after these two participants experienced nonserious
      adverse events. The participant in Arm 1 experienced mild abdominal discomfort,
      diarrhea, sleep disorder, and headache and the participant in Arm 2 experienced
      moderate-intensity abdominal pain and mild vomiting with leukocytosis accompanied
      by elevated pancreatic and hepatic enzymes (aspartate aminotransferase and
      alanine aminotransferase values of 2-fold and 3.5-fold the upper limit of normal,
      respectively). Both participants recovered completely following treatment
      discontinuation. Only limited pharmacokinetic data were generated on these two
      participants. CONCLUSIONS: The early termination of this study precluded drawing
      any definitive conclusions regarding the pharmacokinetics at steady state of
      coadministered saquinavir/ritonavir and efavirenz.

PMID- 19381338
TI  - Spectral preprocessing for clustering time-series gene expressions.
AB  - Based on gene expression profiles, genes can be partitioned into clusters, which
      might be associated with biological processes or functions, for example, cell
      cycle, circadian rhythm, and so forth. This paper proposes a novel clustering
      preprocessing strategy which combines clustering with spectral estimation
      techniques so that the time information present in time series gene expressions
      is fully exploited. By comparing the clustering results with a set of
      biologically annotated yeast cell-cycle genes, the proposed clustering strategy
      is corroborated to yield significantly different clusters from those created by
      the traditional expression-based schemes. The proposed technique is especially
      helpful in grouping genes participating in time-regulated processes.

PMID- 19381340
TI  - An attempt to understand kidney's protein handling function by comparing plasma
      and urine proteomes.
AB  - BACKGROUND: With the help of proteomics technology, the human plasma and urine
      proteomes, which closely represent the protein compositions of the input and
      output of the kidney, respectively, have been profiled in much greater detail by
      different research teams. Many datasets have been accumulated to form "reference
      profiles" of the plasma and urine proteomes. Comparing these two proteomes may
      help us understand the protein handling aspect of kidney function in a way,
      however, which has been unavailable until the recent advances in proteomics
      technology. METHODOLOGY/PRINCIPAL FINDINGS: After removing secreted proteins
      downstream of the kidney, 2611 proteins in plasma and 1522 in urine were
      identified with high confidence and compared based on available proteomic data to
      generate three subproteomes, the plasma-only subproteome, the plasma-and-urine
      subproteome, and the urine-only subproteome, and they correspond to three groups
      of proteins that are handled in three different ways by the kidney. The available
      experimental molecular weights of the proteins in the three subproteomes were
      collected and analyzed. Since the functions of the overrepresented proteins in
      the plasma-and-urine subproteome are probably the major functions that can be
      routinely regulated by excretion from the kidney in physiological conditions,
      Gene Ontology term enrichment in the plasma-and-urine subproteome versus the
      whole plasma proteome was analyzed. Protease activity, calcium and growth factor
      binding proteins, and coagulation and immune response-related proteins were found
      to be enriched. CONCLUSION/SIGNIFICANCE: The comparison method described in this
      paper provides an illustration of a new approach for studying organ functions
      with a proteomics methodology. Because of its distinctive input (plasma) and
      output (urine), it is reasonable to predict that the kidney will be the first
      organ whose functions are further elucidated by proteomic methods in the near
      future. It can also be anticipated that there will be more applications for
      proteomics in organ function research.

PMID- 19381339
TI  - Influence of epinastine hydrochloride, an H1-receptor antagonist, on the function
      of mite allergen-pulsed murine bone marrow-derived dendritic cells in vitro and
      in vivo.
AB  - There is established concept that dendritic cells (DCs) play essential roles in
      the development of allergic immune responses. However, the influence of H(1)
      receptor antagonists on DC functions is not well defined. The aim of the present
      study was to examine the effect of epinastine hydrochloride (EP), the most
      notable histamine H(1) receptor antagonists in Japan, on Dermatophagoides farinae
      (Der f)-pulsed mouse bone marrow-derived DCs in vitro and in vivo. EP at more
      than 25 ng/mL could significantly inhibit the production of IL-6, TNF-alpha and
      IL-10 from Der f-pulsed DCs, which was increased by Der f challenge in vitro. On
      the other hand, EP increased the ability of Der f-pulsed DCs to produce IL-12.
      Intranasal instillation of Der f-pulsed DCs resulted in nasal eosinophilia
      associated with a significant increase in IL-5 levels in nasal lavage fluids. Der
      f-pulsed and EP-treated DCs significantly inhibited nasal eosinophila and reduced
      IL-5. These results indicate that EP inhibits the development of Th2 immune
      responses through the modulation of DC functions and results in favorable
      modification of clinical status of allergic diseases.

PMID- 19381341
TI  - A practical platform for blood biomarker study by using global gene expression
      profiling of peripheral whole blood.
AB  - BACKGROUND: Although microarray technology has become the most common method for
      studying global gene expression, a plethora of technical factors across the
      experiment contribute to the variable of genome gene expression profiling using
      peripheral whole blood. A practical platform needs to be established in order to
      obtain reliable and reproducible data to meet clinical requirements for biomarker
      study. METHODS AND FINDINGS: We applied peripheral whole blood samples with
      globin reduction and performed genome-wide transcriptome analysis using Illumina
      BeadChips. Real-time PCR was subsequently used to evaluate the quality of array
      data and elucidate the mode in which hemoglobin interferes in gene expression
      profiling. We demonstrated that, when applied in the context of standard
      microarray processing procedures, globin reduction results in a consistent and
      significant increase in the quality of beadarray data. When compared to their pre
      globin reduction counterparts, post-globin reduction samples show improved
      detection statistics, lowered variance and increased sensitivity. More
      importantly, gender gene separation is remarkably clearer in post-globin
      reduction samples than in pre-globin reduction samples. Our study suggests that
      the poor data obtained from pre-globin reduction samples is the result of the
      high concentration of hemoglobin derived from red blood cells either interfering
      with target mRNA binding or giving the pseudo binding background signal.
      CONCLUSION: We therefore recommend the combination of performing globin mRNA
      reduction in peripheral whole blood samples and hybridizing on Illumina BeadChips
      as the practical approach for biomarker study.

PMID- 19381342
TI  - Telephone triage service data for detection of influenza-like illness.
AB  - BACKGROUND: Surveillance for influenza and influenza-like illness (ILI) is
      important for guiding public health prevention programs to mitigate the morbidity
      and mortality caused by influenza, including pandemic influenza. Nontraditional
      sources of data for influenza and ILI surveillance are of interest to public
      health authorities if their validity can be established. METHODS/PRINCIPAL
      FINDINGS: National telephone triage call data were collected through automated
      means for purposes of syndromic surveillance. For the 17 states with at least
      500,000 inhabitants eligible to use the telephone triage services, call volume
      for respiratory syndrome was compared to CDC weekly number of influenza isolates
      and percentage of visits to sentinel providers for ILI. The degree to which the
      call data were correlated with either CDC viral isolates or sentinel provider
      percentage ILI data was highly variable among states. CONCLUSIONS: Telephone
      triage data in the U.S. are patchy in coverage and therefore not a reliable
      source of ILI surveillance data on a national scale. However, in states
      displaying a higher correlation between the call data and the CDC data, call data
      may be useful as an adjunct to state-level surveillance data, for example at
      times when sentinel surveillance is not in operation or in areas where sentinel
      provider coverage is considered insufficient. Sufficient population coverage, a
      specific ILI syndrome definition, and the use of a threshold of percentage of
      calls that are for ILI would likely improve the utility of such data for ILI
      surveillance purposes.

PMID- 19381344
TI  - Epithelioid sarcoma of the forearm arising from perineural sheath of median nerve
      mimicking carpal tunnel syndrome.
AB  - We report here a case of epithelioid sarcoma in the forearm of a 33-year-old male
      presenting with symptoms and signs of carpal tunnel syndrome originating from the
      direct involvement of the median nerve. Due to the slow growing of the tumor, the
      patient noticed the presence of tumor mass in his forearm after several months
      from the initial onset of the symptoms. Magnetic resonance imaging showed an 8 x
      4 cm mass involving the median nerve in the middle part of the forearm, and
      histological analysis of the biopsy specimen revealed the diagnosis of
      epithelioid sarcoma. Radical surgical resection was performed in conjunction with
      adjuvant chemotherapy. The function of the flexors were restored by the multiple
      tendon transfers (EIP --> FDS; ECRL --> FDP; BrR --> FPL; EDM --> opponens) with
      superficial cutaneous branch of radial nerve transfer to the resected median
      nerve. The function of the affected hand showed excellent with the DASH
      disability/symptom score of 22.5, and both the grasp power and sensory of the
      median nerve area has recovered up to 50% of the normal side. The patient
      returned to his original vocation and alive with continuous disease free at 3.5
      year follow-up since initial treatment.

PMID- 19381343
TI  - Protein dynamics in individual human cells: experiment and theory.
AB  - A current challenge in biology is to understand the dynamics of protein circuits
      in living human cells. Can one define and test equations for the dynamics and
      variability of a protein over time? Here, we address this experimentally and
      theoretically, by means of accurate time-resolved measurements of endogenously
      tagged proteins in individual human cells. As a model system, we choose three
      stable proteins displaying cell-cycle-dependant dynamics. We find that protein
      accumulation with time per cell is quadratic for proteins with long mRNA life
      times and approximately linear for a protein with short mRNA lifetime. Both
      behaviors correspond to a classical model of transcription and translation. A
      stochastic model, in which genes slowly switch between ON and OFF states,
      captures measured cell-cell variability. The data suggests, in accordance with
      the model, that switching to the gene ON state is exponentially distributed and
      that the cell-cell distribution of protein levels can be approximated by a Gamma
      distribution throughout the cell cycle. These results suggest that relatively
      simple models may describe protein dynamics in individual human cells.

PMID- 19381345
TI  - Empirical efficiency maximization: improved locally efficient covariate
      adjustment in randomized experiments and survival analysis.
AB  - It has long been recognized that covariate adjustment can increase precision in
      randomized experiments, even when it is not strictly necessary. Adjustment is
      often straightforward when a discrete covariate partitions the sample into a
      handful of strata, but becomes more involved with even a single continuous
      covariate such as age. As randomized experiments remain a gold standard for
      scientific inquiry, and the information age facilitates a massive collection of
      baseline information, the longstanding problem of if and how to adjust for
      covariates is likely to engage investigators for the foreseeable future. In the
      locally efficient estimation approach introduced for general coarsened data
      structures by James Robins and collaborators, one first fits a relatively small
      working model, often with maximum likelihood, giving a nuisance parameter fit in
      an estimating equation for the parameter of interest. The usual advertisement is
      that the estimator will be asymptotically efficient if the working model is
      correct, but otherwise will still be consistent and asymptotically Gaussian.
      However, by applying standard likelihood-based fits to misspecified working
      models in covariate adjustment problems, one can poorly estimate the parameter of
      interest. We propose a new method, empirical efficiency maximization, to optimize
      the working model fit for the resulting parameter estimate. In addition to the
      randomized experiment setting, we show how our covariate adjustment procedure can
      be used in survival analysis applications. Numerical asymptotic efficiency
      calculations demonstrate gains relative to standard locally efficient estimators

PMID- 19381346
TI  - Molecular evidence of senescence in corneal endothelial cells of senescence
      accelerated mice.
AB  - PURPOSE: To investigate senescent evidence in corneal endothelial cells (CECs) of
      the senescence-accelerated mouse (SAM), which is considered a suitable animal
      model for the further study of the senescent mechanism in CECs. METHODS: Thirty
      six male mice from a senescence resistant mouse strain (SAM R1) and a senescence
      prone strain (SAM P8) at various ages (1, 6, and 12 months) were analyzed in this
      study. The endothelial cell density (ECD) and cell viability were detected using
      trypan blue and alizarin red dyes while the senescent cells were observed by
      senescence-associated beta-galactosidase (SA-beta-Gal; pH 6.0) staining. In
      addition, ultrastructure was observed using an electron microscope. The
      senescence-related genes (p16(INK4a), p19(ARF), p21(WAF1/CIP1), and p53) in the
      CECs were visualized via immunohistochemistry and were quantitatively detected
      using real-time polymerase chain reaction (PCR). Signal proteins of phospho
      extracellular signal-regulated kinase 1/2 (p-ERK 1/2) were detected by western
      blot analysis. RESULTS: Our results indicated that the ECD values decreased with
      increasing age in both the SAM-R1 and SAM P8 series where the values in the older
      SAM p8 series decreased even lower than in the older SAM R1 series. The mean
      decreased rate was 2.276% per month in the SAM R1 and 2.755% per month in the SAM
      P8 series. In addition, changes in the senescence-like ultrastructure were
      observed in the CECs of both strains, and the increase in the positive staining
      of SA-beta-Gal was observed in both strains as well. It is worth noting that such
      changes were more significant in the SAM P8 strain. Immunohistochemical detection
      assays indicated the expression of p-ERK 1/2, p16(INK4a), p19(ARF),
      p21(WAF1/CIP1), and p53 (nuclear localization for each) in each age group
      analyzed. Furthermore, the results of real-time PCR studies showed an increase in
      the expression of p16(INK4a) mRNA as a function of age in the SAM R1 strain and
      in the early senescence stage of the SAM P8 strain in addition to an increase in
      the expression of p21(WAF1/CIP1) and p53 mRNA as a function of age in the SAM P8
      strain (no significant increase was observed in the SAM R1 strain). Additional
      results from western blot analysis demonstrated an age-related increase in the
      quantity of the p-ERK 1/2 proteins in both strains. CONCLUSIONS: The SAM R1 and
      SAM P8 strains represent suitable models for the study of CEC senescence in vivo.
      In addition, the progression of cellular senescence in CECs occurs more quickly
      in the SAM P8 strain as opposed to the SAM R1 strain. Our results also indicate
      that the p16(INK4a) signaling pathway may play a key role in the early stages of
      senescence in CECs while the p53/p21(WAF1/CIP1) signaling pathway may exert its
      principle effect in the late stages of senescence in CECs. Further study is still
      required about the role of the mitogen-activated protein kinase (MAPK) signaling
      cascade in the process of senescence in CECs.

PMID- 19381347
TI  - Single nucleotide polymorphisms of the tenomodulin gene (TNMD) in age-related
      macular degeneration.
AB  - PURPOSE: Tenomodulin (TNMD) is located in the X-chromosome encoding a putative
      angiogenesis inhibitor which is expressed in retina. Associations of single
      nucleotide polymorphisms of TNMD with the prevalence of age-related macular
      degeneration (AMD) were examined. METHODS: Six markers covering 75% of the common
      sequence variation in the coding region of TNMD and 10 kb up- and downstream were
      genotyped in a sample consisting of 89 men and 175 women with exudative AMD, 18
      men and 25 women with atrophic AMD, and 55 men and 113 women without AMD. All
      participants were over 65 years old and did not have diabetes mellitus. Due to
      the chromosomal locus, the association of genotypes with AMD was assessed
      genderwise. RESULTS: Three markers, rs1155974, rs2073163, and rs7890586, were
      associated with a risk of AMD in women. In comparison to women with other
      genotypes, the women who were homozygous for the minor allele (genotypes
      rs1155974-TT or rs2073163-CC) had 2.6 fold (p=0.021) or 1.9 fold (p=0.067) risk
      for having AMD, respectively. These differences were due to the unequal
      prevalence of exudative AMD. In comparison to women who were homozygous for the
      major alleles, the women with rs1155974-TT genotype had a 2.8 fold risk (p=0.021
      in additive model; p=0.022 in recessive model) for exudative AMD, and the women
      with rs2073163-CC genotype had a 1.8 fold risk (p=0.09 in additive model; p=0.038
      in recessive model). Furthermore, women carrying the rare rs7890586-AA genotype
      had a significantly smaller risk for having AMD than women with the other
      genotypes (odds ratio 0.083; p=0.001 in recessive model), but due to the low
      frequency of this genotype, this finding must be interpreted cautiously. The
      false discovery rate was <10% for all of the aforementioned results. CONCLUSIONS:
      On the basis of the putative antiangiogenic role of TNMD and the present genetic
      associations of TNMD with AMD in women, we suggest that TNMD could be a novel
      candidate gene for AMD. These results should be confirmed in further studies.

PMID- 19381348
TI  - Old can be new again: HAPPY whole genome sequencing, mapping and assembly.
AB  - During the last three decades, both genome mapping and sequencing methods have
      advanced significantly to provide a foundation for scientists to understand
      genome structures and functions in many species. Generally speaking, genome
      mapping relies on genome sequencing to provide basic materials, such as DNA
      probes and markers for their localizations, thus constructing the maps. On the
      other hand, genome sequencing often requires a high-resolution map as a skeleton
      for whole genome assembly. However, both genome mapping and sequencing have never
      come together in one pipeline. After reviewing mapping and next-generation
      sequencing methods, we would like to share our thoughts with the genome community
      on how to combine the HAPPY mapping technique with the new-generation sequencing,
      thus integrating two systems into one pipeline, called HAPPY pipeline. The
      pipeline starts with preparation of a HAPPY panel, followed by multiple
      displacement amplification for producing a relatively large quantity of DNA.
      Instead of conventional marker genotyping, the amplified panel DNA samples are
      subject to new-generation sequencing with barcode method, which allows us to
      determine the presence/absence of a sequence contig as a traditional marker in
      the HAPPY panel. Statistical analysis will then be performed to infer how close
      or how far away from each other these contigs are within a genome and order the
      whole genome sequence assembly as well. We believe that such a universal approach
      will play an important role in genome sequencing, mapping, and assembly of many
      species; thus advancing genome science and its applications in biomedicine and
      agriculture.

PMID- 19381350
TI  - Clinical symptoms associated with asystolic or bradycardic responses on
      implantable loop recorder monitoring in patients with recurrent syncope.
AB  - BACKGROUND: Implantable loop recorders (ILR) have been found to be useful in the
      diagnosis and management of syncope of unclear etiology. The clinical symptoms of
      abnormalities seen during ILR monitoring have not been adequately studied. AIM:
      The aim of this retrospective study was to determine the clinical symptoms which
      were the best predictors of asystolic or bradycardic responses during ILR
      monitoring. METHODS: Patients with either asystole or bradycardia recorded during
      ILR monitoring were analyzed from our database. The clinical characteristics of
      these patients were compared to the patients with ILR's who did not have recorded
      bradycardic episodes. The episodes were characterized as being convulsive or
      nonconvulsive, brief (<5 minutes) or prolonged (> 5 minutes), and having had a
      prodrome or no prodrome. RESULTS: Eleven patients (4 males and 7 females; age 39
      +/-11 years) had asystole or bradycardia on ILR monitoring. Eleven patients (2
      males and 9 females; age 46+/-23) had no bradycardiac events. Palpitations,
      convulsive syncope, prolonged episode, and prodrome were present in 37% vs. 74%
      (P = 0.125), 62% vs. 0% (P = 0.002), 87% vs. 0% (P=0), and 73% vs. 13% (P=0.009)
      patients, respectively, in the asystole/bradycardia and non-bradycardia groups.
      In the asystole/bradycardia group eight patients had bradycardia (HR < 20) for >
      10 seconds and three patients had asystole >10 seconds. CONCLUSION: Convulsive
      syncope, prolonged loss of consciousness during syncopal episode, and absence of
      prodrome or aura are clinical predictors of asystole or bradycardia on ILR
      monitoring.

PMID- 19381349
TI  - Vesnarinone represses the fibrotic changes in murine lung injury induced by
      bleomycin.
AB  - We investigated the potential usefulness of vesnarinone, a novel cytokine
      inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin
      (BLM)-induced pulmonary fibrosis. Mice were fed a control diet (n=42), or a diet
      containing low (n=42) or high (n=42) dose of vesnarinone. Dietary intake of
      vesnarinone minimized the BLM toxicity as reflected by significant decreases in
      numbers of inflammatory cells, KC, and soluble TNF receptors in the
      bronchoalveolar lavage fluid. A quantitative evaluation of histology demonstrated
      significantly mild lung parenchymal lesions in BLM-treated mice fed with diet
      containing high dose of vesnarinone than in the control diet group. Consistent
      with the histopathology, hydroxyproline levels in lung tissue from BLM-treated
      mice fed with diet containing vesnarinone were significantly lower than that from
      mice fed with control diet. We concluded that vesnarinone inhibits BLM-induced
      pulmonary fibrosis, at least in part, by the inhibition of acute lung injuries in
      the early phase.

PMID- 19381352
TI  - Nonparametric variance estimation in the analysis of microarray data: a
      measurement error approach.
AB  - This article investigates the effects of measurement error on the estimation of
      nonparametric variance functions. We show that either ignoring measurement error
      or direct application of the simulation extrapolation, SIMEX, method leads to
      inconsistent estimators. Nevertheless, the direct SIMEX method can reduce bias
      relative to a naive estimator. We further propose a permutation SIMEX method
      which leads to consistent estimators in theory. The performance of both SIMEX
      methods depends on approximations to the exact extrapolants. Simulations show
      that both SIMEX methods perform better than ignoring measurement error. The
      methodology is illustrated using microarray data from colon cancer patients.

PMID- 19381351
TI  - Comparison of a two-lead, computerized, resting ECG signal analysis device, the
      MultiFunction-CardioGram or MCG (a.k.a. 3DMP), to quantitative coronary
      angiography for the detection of relevant coronary artery stenosis (>70%) - a
      meta-analysis of all published trials performed and analyzed in the US.
AB  - BACKGROUND: Accurate, non-invasive diagnosis of, and screening for, coronary
      artery disease (CAD) and restenosis after coronary revascularization has been a
      challenge due to either low sensitivity/specificity or relevant morbidity
      associated with current diagnostic modalities. METHODS: To assess sensitivity and
      specificity of a new computerized, multiphase, resting electrocardiogram analysis
      device (MultiFunction-CardioGram(sm) or MCG a.k.a. 3DMP) for the detection of
      relevant coronary stenosis (>70%), a meta-analysis of three published prospective
      trials performed in the US on patient data collected using the US manufactured
      device and analyzed using the US-based software and New York data analysis center
      from patients in the US, Germany, and Asia was completed. A total of 1076
      patients from the three trials (US - 136; Germany - 751; Asia - 189) (average age
      62 +/- 11.5, 65 for women, 60 for men) scheduled for coronary angiography, were
      included in the analysis. Patients enrolled in the trials may or may not have had
      prior angiography and/or coronary intervention. Angiographic results in all
      studies were classified for hemodynamically relevant stenosis (> 70%) by two US
      based angiographers independently. RESULTS: Hemodynamically relevant stenosis was
      diagnosed in 467 patients (43.4%). The device, after performing a frequency
      domain, computational analysis of the resting ECG leads and computer-database
      comparison, calculated a coronary ischemia "severity" score from 0 to 20 for each
      patient. The severity score was significantly higher for patients with relevant
      coronary stenosis (5.4 +/- 1.8 vs. 1.7 +/- 2.1). The study device (using a cut
      off score for relevant stenosis of 4.0) correctly classified 941 of the 1076
      patients with or without relevant stenosis (sensitivity-91.2%; specificity-84.6%;
      NPV 0.942, PPV 0.777). Adjusted positive and negative predictive values (PPV and
      NPV) were 81.9% and 92.6%, respectively (ROC AUC = 0.881 [95% CI: 0.860-0.903]).
      Subgroup analysis showed no significant influence of sex, age, race/nationality,
      previous revascularization procedures, resting ECG morphology, or participating
      center on the device's diagnostic performance. CONCLUSIONS: The new computerized,
      multiphase, resting ECG analysis device (MultiFunction-CardioGram(sm)) has been
      shown in this meta-analysis to safely and accurately identify patients with
      relevant coronary stenosis (>70%) with high sensitivity and specificity and high
      negative predictive value. Its potential use in the evaluation of symptomatic
      patients suspected to suffer from coronary disease/ischemia is discussed.

PMID- 19381353
TI  - Experimentally validated quantitative linear model for the device physics of
      elastomeric microfluidic valves.
AB  - A systematic experimental study and theoretical modeling of the device physics of
      polydimethylsiloxane "pushdown" microfluidic valves are presented. The phase
      space is charted by 1587 dimension combinations and encompasses 45-295 MUm
      lateral dimensions, 16-39 MUm membrane thickness, and 1-28 psi closing pressure.
      Three linear models are developed and tested against the empirical data, and then
      combined into a fourth-power-polynomial superposition. The experimentally
      validated final model offers a useful quantitative prediction for a valve's
      properties as a function of its dimensions. Typical valves (80-150 MUm width) are
      shown to behave like thin springs.

PMID- 19381355
TI  - C-arm based cone-beam CT using a two-concentric-arc source trajectory: system
      evaluation.
AB  - The current x-ray source trajectory for C-arm based cone-beam CT is a single arc.
      Reconstruction from data acquired with this trajectory yields cone-beam artifacts
      for regions other than the central slice. In this work we present the preliminary
      evaluation of reconstruction from a source trajectory of two concentric arcs
      using a flat-panel detector equipped C-arm gantry (GE Healthcare Innova 4100
      system, Waukesha, Wisconsin). The reconstruction method employed is a summation
      of FDK-type reconstructions from the two individual arcs. For the angle between
      arcs studied here, 30 degrees , this method offers a significant reduction in the
      visibility of cone-beam artifacts, with the additional advantages of simplicity
      and ease of implementation due to the fact that it is a direct extension of the
      reconstruction method currently implemented on commercial systems. Reconstructed
      images from data acquired from the two arc trajectory are compared to those
      reconstructed from a single arc trajectory and evaluated in terms of spatial
      resolution, low contrast resolution, noise, and artifact level.

PMID- 19381354
TI  - Endogenous Bioactive Lipids and the Regulation of Conventional Outflow Facility.
AB  - Perturbation of paracrine signaling within the human conventional outflow pathway
      influences tissue homeostasis and outflow function. For example, exogenous
      introduction of the bioactive lipids, sphingosine-1-phosphate, anandamide or
      prostaglandin F(2alpha), to conventional outflow tissues alters the rate of
      drainage of aqueous humor through the trabecular meshwork, and into Schlemm's
      canal. This review summarizes recent data that characterizes endogenous bioactive
      lipids, their receptors and associated signaling partners in the conventional
      outflow tract. We also discuss the potential of targeting such signaling pathways
      as a strategy for the development of therapeutics to treat ocular hypertension
      and glaucoma.

PMID- 19381357
TI  - Diversity-oriented fluorescence library approach for the discovery of sensors and
      probes.
AB  - Fluorescent small molecules have received considerable attention due to their
      potential for chemosensing and bioimaging. A conventional strategy for probe
      development is a target-oriented approach based on known molecular recognition
      mechanisms for individual analytes. However, sophisticated rational design does
      not always guarantee the applicability of probes in complex biological systems.
      Therefore the speed and the scope of sensor development has been limited. To
      overcome these limitations, diversity-oriented fluorescence library approaches
      have been applied to develop new fluorescent probes in the absence of knowledge
      about the target recognition mechanism. This review summarizes recent advances in
      fluorescent probe development facilitated by diversity-oriented library
      approaches.

PMID- 19381356
TI  - Lactobacillus fermentum ME-3 - an antimicrobial and antioxidative probiotic.
AB  - The paper lays out the short scientific history and characteristics of the new
      probiotic Lactobacillus fermentum strain ME-3 DSM-14241, elaborated according to
      the regulations of WHO/FAO (2002). L. fermentum ME-3 is a unique strain of
      Lactobacillus species, having at the same time the antimicrobial and
      physiologically effective antioxidative properties and expressing health
      promoting characteristics if consumed. Tartu University has patented this strain
      in Estonia (priority June 2001, patent in 2006), Russia (patent in 2006) and the
      USA (patent in 2007). The paper describes the process of the identification and
      molecular typing of this probiotic strain of human origin, its deposition in an
      international culture collection, and its safety assessment by laboratory tests
      and testing on experimental animals and volunteers. It has been established that
      L. fermentum strain ME-3 has double functional properties: antimicrobial activity
      against intestinal pathogens and high total antioxidative activity (TAA) and
      total antioxidative status (TAS) of intact cells and lysates, and it is
      characterized by a complete glutathione system: synthesis, uptake and redox
      turnover. The functional efficacy of the antimicrobial and antioxidative
      probiotic has been proven by the eradication of salmonellas and the reduction of
      liver and spleen granulomas in Salmonella Typhimurium-infected mice treated with
      the combination of ofloxacin and L. fermentum strain ME-3. Using capsules or
      foodstuffs enriched with L. fermentum ME-3, different clinical study designs
      (including double-blind, placebo-controlled, crossover studies) and different
      subjects (healthy volunteers, allergic patients and those recovering from a
      stroke), it has been shown that this probiotic increased the antioxidative
      activity of sera and improved the composition of the low-density lipid particles
      (LDL) and post-prandial lipids as well as oxidative stress status, thus
      demonstrating a remarkable anti-atherogenic effect. The elaboration of the
      probiotic L. fermentum strain ME-3 has drawn on wide international cooperative
      research and has taken more than 12 years altogether. The new ME-3 probiotic
      containing products have been successfully marketed and sold in Baltic countries
      and Finland.

PMID- 19381359
TI  - Transfection microarray and the applications.
AB  - Microarray transfection has been extensively studied for high-throughput
      functional analysis of mammalian cells. However, control of efficiency and
      reproducibility are the critical issues for practical use. By using solid-phase
      transfection accelerators and nano-scaffold, we provide a highly efficient and
      reproducible microarray-transfection device, "transfection microarray". The
      device would be applied to the limited number of available primary cells and stem
      cells not only for large-scale functional analysis but also reporter-based time
      lapse cellular event analysis.

PMID- 19381360
TI  - Caged AG10: new tools for spatially predefined mitochondrial uncoupling.
AB  - The study of mitochondria and mitochondrial Ca2+ signalling in localised regions
      is hampered by the lack of tools that can uncouple the mitochondrial membrane
      potential (DeltaPsi(m)) in a spatially predefined manner. Although there are a
      number of existing mitochondrial uncouplers, these compounds are necessarily
      membrane permeant and therefore exert their actions in a spatially unselective
      manner. Herein, we report the synthesis of the first caged (photolabile
      protected) mitochondrial uncouplers, based on the tyrphostin AG10. We have
      analysed the laser photolysis of these compounds, using (1)H NMR and HPLC, and
      demonstrate that the major product of caged AG10 photolysis is AG10. It is shown
      that photolysis within single smooth muscle cells causes a collapse of
      DeltaPsi(m) consistent with photorelease of AG10. Furthermore, the effect of the
      photoreleased AG10 is localised to a subcellular region proximal to the site of
      photolysis, demonstrating for the first time spatially predefined mitochondrial
      uncoupling.

PMID- 19381361
TI  - Proteomic profiling of the stem cell response to retinoic acid and synthetic
      retinoid analogues: identification of major retinoid-inducible proteins.
AB  - The natural retinoid, all-trans retinoic acid (ATRA), is widely used to direct
      the in vitro differentiation of stem cells. However, substantial degradation and
      isomerisation of ATRA in response to UV-vis light has serious implications with
      regard to experimental reproducibility and standardisation. We present the novel
      application of proteomic biomarker profiling technology to stem cell lysates to
      rapidly compare the differentiation effects of ATRA with those of two stable
      synthetic retinoid analogues, EC19 and EC23, which have both been shown to induce
      differentiation in the embryonal carcinoma cell line TERA2.cl.SP12. MALDI-TOF MS
      (matrix-assisted laser desorption ionisation time-of-flight mass spectrometry)
      protein profiles support previous findings into the functional relationships
      between these compounds in the TERA2.cl.SP12 line. Subsequent analysis of protein
      peak data enabled the semi-quantitative comparison of individual retinoid
      responsive proteins. We have used ion exchange chromatographic protein separation
      to enrich for retinoid-inducible proteins, thereby facilitating their
      identification from SDS-PAGE gels. The cellular retinoid-responsive proteins
      CRABP-I, CRABP-II, and CRBP-I were up-regulated in response to ATRA and EC23,
      indicating a bona fide retinoid pathway response to the synthetic compound. In
      addition, the actin filament regulatory protein profilin-1 and the microtubule
      regulator stathmin were also elevated following treatment with both ATRA and
      EC23. The up-regulation of profilin-1 and stathmin associated with retinoid
      induced neural differentiation correlates with their known roles in cytoskeletal
      reorganisation during axonal development. Immunological analysis via western
      blotting confirmed the identification of CRABP-I, profilin-1 and stathmin, and
      supported their observed regulation in response to the retinoid treatments.

PMID- 19381362
TI  - A chemical proteomics based enrichment technique targeting the interactome of the
      PDE5 inhibitor PF-4540124.
AB  - The starting point for the discovery and development of new drugs is the design
      of molecules that bind to their target proteins with high specificity. Here we
      describe a systematic chemical proteomics based approach, whereby we use a novel
      PDE5 inhibitor as bait in mice lung tissue. The compound N-(6-aminohexyl)-3-(1
      ethyl-3-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4
      propoxybenzenesulfonamide (or PF-4540124), which binds to phosphodiesterase-5
      (PDE5) with high affinity, was therefore immobilized on an affinity support.
      Initial affinity enrichment revealed the binding of hundreds of proteins to this
      immobilized PDE5 inhibitor. Therefore, selective pre-clearing and elution
      protocols were designed and used in combination with differential stable-isotope
      labeling to discriminate between the specific binding of low abundant proteins
      and less specific binding of high abundant proteins. The optimized method allowed
      us to selectively analyze the "interactome" of the PDE5 inhibitor PF-4540124 and
      enabled us to identify different isoforms of PDE5 present in mouse lung.
      Additionally, we enriched for the prenyl binding protein PrBP, which is also
      known as PDE6delta. Further analysis, applying in vitro binding assays allowed us
      to verify PrBP as a novel interactor of PF-4540124. The presented method provides
      a generic highly-specific chemical proteomics based enrichment technique for
      analyzing drug-protein interactions in mammalian tissue lysates.

PMID- 19381363
TI  - Systems biology evaluation of immune responses induced by human host defence
      peptide LL-37 in mononuclear cells.
AB  - The immune system is very complex, it involves the integrated regulation and
      expression of hundreds of proteins. To understand in greater detail how the human
      host defence immunomodulatory peptide LL-37 interacts with innate immunity, a
      systems approach was pursued. Polychromatic flow cytometry was employed to
      demonstrate that within human peripheral blood mononuclear cells, CD14+
      monocytes, myeloid and plasmocytoid dendritic cells and T- and B-lymphocytes, all
      responded to LL-37, with the differential production of intracellular cytokines.
      Microarray analyses with CD14+ monocytes indicated the differential expression of
      475 genes in response to stimulation with LL-37. To understand this complex
      response, bioinformatic interrogation, using InnateDB, of the gene ontology,
      signalling pathways and transcription factor binding sites was undertaken.
      Activation of the IkappaBalpha/NFkappaB, mitogen-activated protein kinases p38,
      ERK1/2 and JNK, and PI3K signalling pathways in response to LL-37 was
      demonstrated by pathway and ontology over-representation analyses, and confirmed
      experimentally by inhibitor studies. Computational analysis of the predicted
      transcription factor binding sites upstream of the genes that were regulated by
      LL-37 predicted the involvement of several transcription factors including
      NFkappaB and five novel factors, AP-1, AP-2, SP-1, E2F1, and EGR, which were
      experimentally confirmed to respond to LL-37 by performing transcription factor
      array studies on nuclear extracts from LL-37 treated mononuclear cells. These
      data are discussed as reflecting the integration of several responsive signalling
      pathways through the involvement of transcription factor complexes in gene
      expression activated by LL-37 in human mononuclear cells.

PMID- 19381364
TI  - Copper(II) coordination outside the tandem repeat region of an unstructured
      domain of chicken prion protein.
AB  - Combined potentiometric, calorimetric and spectroscopic methods were used to
      investigate the Cu(2+) binding ability and coordination behaviour of some peptide
      fragments related to the neurotoxic region of chicken Prion Protein. The systems
      studied were the following protein fragments: chPrP(106-114), chPrP(119-126),
      chPrP(108-127), chPrP(105-127) and chPrP(105-133).The complex formation always
      starts around pH 4 with the coordination of an imidazole nitrogen, followed by
      the deprotonation and binding of amide nitrogens from the peptidic backbone. At
      neutral pH, the {N(im), 3N(-)} binding mode is the preferred one. The amide
      nitrogens participating in the binding to the Cu(2+) ion derive from residues
      from the N-terminus side, with the formation of a six-membered chelate ring with
      the imidazolic side chain.Comparison of thermodynamic data for the two histydyl
      binding domains (around His-110 and His-124), clearly indicates that the closest
      to the hexarepeat domain (His-110) has the highest ability to bind Cu(2+) ions,
      although both of them have the same coordination mode. Conversely, in the case of
      the human neurotoxic peptide region, between the two binding sites, located at
      His-96 and His-111, the farthest from the tandem repeat region is the strongest
      one. Finally, thermodynamic data show that chicken peptide is a distinctly better
      ligand for coordination of copper ions with respect to the human fragment.

PMID- 19381365
TI  - Preliminary kinetic analysis of acyl carrier protein-ketoacylsynthase
      interactions in the actinorhodin minimal polyketide synthase.
AB  - Interactions between the acyl carrier protein (ACP) and ketoacylsynthase (KS)
      components of the actinorhodin polyketide synthase have been investigated using
      kinetic assays. These indicate that for three different quantifiable interactions
      (acceleration of self-malonylation, initiation and extension) mutations of E47
      and E53 residues located on ACP helix II have different effects. Initiation
      clearly involves interaction between KS(beta) and ACP helix II, but self
      malonylation acceleration and extension by KS(alpha) appear not to be affected
      strongly by the same mutations.

PMID- 19381358
TI  - A general map of iron metabolism and tissue-specific subnetworks.
AB  - Iron is required for survival of mammalian cells. Recently, understanding of iron
      metabolism and trafficking has increased dramatically, revealing a complex,
      interacting network largely unknown just a few years ago. This provides an
      excellent model for systems biology development and analysis. The first step in
      such an analysis is the construction of a structural network of iron metabolism,
      which we present here. This network was created using CellDesigner version 3.5.2
      and includes reactions occurring in mammalian cells of numerous tissue types. The
      iron metabolic network contains 151 chemical species and 107 reactions and
      transport steps. Starting from this general model, we construct iron networks for
      specific tissues and cells that are fundamental to maintaining body iron
      homeostasis. We include subnetworks for cells of the intestine and liver, tissues
      important in iron uptake and storage, respectively, as well as the reticulocyte
      and macrophage, key cells in iron utilization and recycling. The addition of
      kinetic information to our structural network will permit the simulation of iron
      metabolism in different tissues as well as in health and disease.

PMID- 19381366
TI  - Differential cold-adaptation among protein components of the thioredoxin system
      in the psychrophilic eubacterium Pseudoalteromonas haloplanktis TAC 125.
AB  - Thioredoxin and thioredoxin reductase from the psychrophilic eubacterium
      Pseudoalteromonas haloplanktis were obtained as recombinant His-tagged proteins
      (rPhTrx and rPhTrxR, respectively). rPhTrxR is organised as a homodimeric
      flavoenzyme, whereas rPhTrx is a small monomeric protein, both containing a
      functional disulfide bridge. However, three additional cysteines are present as
      free thiols in purified rPhTrxR. When individually tested in specific assays,
      rPhTrxR and rPhTrx display a full activity at low temperatures, an indispensable
      requirement for cold-adapted proteins. In particular, rPhTrxR catalyses the NADPH
      dependent reduction of DTNB and rPhTrx provokes the insulin precipitation in the
      presence of DTT. The analysis of the effect of temperature on these reactions
      indicates that rPhTrxR is more cold-adapted than rPhTrx, having a higher
      psychrophilicity. The combined activity of rPhTrxR and rPhTrx, tested in a
      reconstituted assay containing NADPH as electrons donor and human insulin as the
      thioredoxin substrate, demonstrates a direct functional interaction between the
      purified recombinant components of the thioredoxin system of P. haloplanktis.
      Furthermore, the NADPH-dependent reduction of rPhTrx catalysed by rPhTrxR is
      fully reversible and allows the determination of its redox potential, whose value
      is in the range of other bacterial and archaeal thioredoxins. The analysis of the
      thermostability of rPhTrxR points to its discrete heat resistance. However,
      rPhTrx is much more heat resistant, with a half inactivation time of about 4 h at
      95 degrees C. This exceptional heat resistance for a psychrophilic protein is
      significantly decreased by the reduction of the disulfide bridge of rPhTrx.
      Functionality, thermodependence and thermostability of the P. haloplanktis
      thioredoxin system point to the relevance of this key mechanism for the
      preservation of the reduced state of cytoplasmic proteins even in a cold-adapted
      source.

PMID- 19381368
TI  - Folding of single-stranded DNA quadruplexes containing an autonomously stable
      mini-hairpin loop.
AB  - The single-stranded DNA quadruplex motif TG(3)-L(1)-G(3)-L(2)-G(3)-L(3)-G(3)T
      (where L(1), L(2) and L(3) are the three loop sequences) was used as a template
      for probing the effects of the loop sequences on stability and folding topology.
      An autonomously stable mini-hairpin sequence (ACGTAGT) was inserted into the
      central loop (L(2)) of different sequences with intrinsic propensities to form
      either parallel or anti-parallel structures. Single nucleotides (T) at positions
      L(1) and L(3) strongly favour the formation of a parallel structure with the L(2)
      hairpin insert affecting stability in the same way as a T(7) loop. However, in
      the context of an anti-parallel quadruplex with T(3) loops in positions L(1) and
      L(3), the mini-hairpin in the central loop forms a stable structure which
      enhances the T(m) of the quadruplex by approximately 10 degrees C when compared
      with the T(7) insert. The CD and UV melting data show that base pairing
      interactions within the ACGTAGT hairpin loop sequence, when accommodated as a
      diagonal loop in an anti-parallel structure, can enhance stability and lead to
      novel quadruplex structures, adding complexity to the folding landscape and
      expanding the potential repertoire of sequences that are able to regulate gene
      expression in vivo.

PMID- 19381369
TI  - Real-time apta-PCR for 20 000-fold improvement in detection limit.
AB  - A real-time apta-PCR for the ultrasensitive detection of thrombin is reported,
      where the thrombin aptamer acts not only as a biomolecular recognition element,
      but also as a label for amplification via real-time PCR. Aptamers can be easily
      converted to a reporter agent for detection by real-time PCR, simply via flanking
      of the aptamer's recognition moiety with primer sequences. The reported technique
      has the advantage of the ultrasensitivity achievable with immuno-PCR, but without
      the complications of addition of a DNA label, and is a technique generically
      applicable to all aptamers. Here, we use a sandwich format, where two existing
      thrombin binding aptamers with distinct binding epitopes have been utilised to
      capture and detect thrombin in a streptavidin-coated microtiter plate. The amount
      of thrombin is calculated from real-time PCR analysis of eluted captured reporter
      aptamer. However, the technique can also be used for aptamer-antibody sandwiches,
      or simply with single aptamers. A greater than 20 000-fold increase in
      sensitivity is achieved, highlighting the potential of this approach for the
      detection of very low levels of target analytes. The use of the aptamer itself as
      the reporter molecule eliminates the necessity of laborious enzyme/DNA labelling,
      facilitating a significantly more straightforward assay with a vastly enhanced
      sensitivity.

PMID- 19381367
TI  - Targeted lipidomic analysis of oxysterols in the embryonic central nervous
      system.
AB  - In this study two regions of embryonic (E11) mouse central nervous system (CNS)
      have been profiled for their unesterified sterol content. Using high-performance
      liquid chromatography (HPLC)-mass spectrometry (MS) and tandem mass spectrometry
      (MS(n)) low levels of oxysterols (estimated 2-165 ng g(-1) wet weight) were
      identified in cortex (Ctx) and spinal cord (Sc). The identified oxysterols
      include 7 alpha-, 7 beta-, 22R-, 24S-, 25- and 27-hydroxycholesterol; 24,25- and
      24,27-dihydroxycholesterol; and 24S,25-epoxycholesterol. Of these, 24S
      hydroxycholesterol is biosynthesised exclusively in brain. In comparison to adult
      mouse where the 24S-hydroxycholesterol level is about 40 microg g(-1) in brain
      the level of 24S-hydroxycholesterol reported here (estimated 26 ng g(-1) in Ctx
      and 13 ng g(-1) in Sc) is extremely low. Interestingly, the level of 24S,25
      epoxycholesterol in both CNS regions (estimated 165 ng g(-1) in Ctx and 91 ng g(
      1) in Sc) is somewhat higher than the levels of the hydroxycholesterols. This
      oxysterol is formed in parallel to cholesterol via a shunt of the mevalonate
      pathway and its comparatively high abundance may be a reflection of a high rate
      of cholesterol synthesis at this stage of development. Levels of cholesterol
      (estimated 1.25 mg g(-1) in Ctx and 1.15 mg g(-1) in Sc) and its precursors were
      determined by gas chromatography-mass spectrometry (GC-MS). In both CNS regions
      cholesterol levels were found to be lower than those reported in the adult, but
      in relation to cholesterol the levels of cholesterol precursors were higher than
      found in adult indicating a high rate of cholesterol synthesis. In summary, our
      data provide evidence for the presence of endogenous oxysterols in two brain
      regions of the developing CNS. Moreover, while most of the enzymes involved in
      hydroxysterol synthesis are minimally active at E11, our results suggest that the
      mevalonate pathway is significantly active, opening up the possibility for a
      function of 24S,25-epoxycholesterol during brain development.

PMID- 19381370
TI  - Bioanalysis of recombinant proteins and antibodies by mass spectrometry.
AB  - In recent years, biotechnologically-derived drugs have been a major focus of
      research and development in the pharmaceutical industry. Their pharmacokinetics
      and pharmacokinetic/pharmacodynamic relationships impact every stage of the
      development process and require their assessment in the circulation in
      preclinical species and in humans. To this end, immunoassays are a reference, but
      standardisation remains an issue owing to the restricted pattern of antibody
      specificity and interference with endogenous components. As an alternative, we
      report here analytical strategies involving liquid chromatography coupled to mass
      spectrometry (LC-MS) for the accurate quantification of therapeutic proteins and
      antibodies in biological fluids.

PMID- 19381371
TI  - Linker immobilization of protein and oligonucleotide on indium-tin-oxide for
      detection of probe-target interactions by Kelvin physics.
AB  - This work describes a label-free microarray analysis technique capable of
      detecting biomolecule target interactions with probes being anchored with a new
      linker-diluent system on indium-tin-oxide. The method is based on the
      differential work function characteristics of the substrate measured by a
      scanning Kelvin nanoprobe in terms of contact potential difference signals.

PMID- 19381372
TI  - In vivo recognition of Bacillus subtilis by desorption electrospray ionization
      mass spectrometry (DESI-MS).
AB  - Desorption electrospray ionization mass spectrometry (DESI-MS) of culture of the
      bacterium Bacillus subtilis as a biofilm growing on agar nutrient gives simple,
      high quality mass spectra dominated in both the positive and negative ion modes
      by signals due to the cyclic lipopeptide, Surfactin(C15). This in vivo
      experiment, performed by direct analysis of untreated microorganism samples under
      ambient conditions, allows rapid identification of this microorganism and the
      antibiotics that it produces. The result is suggestive of the capabilities of
      DESI-MS for in vivo microorganism characterization in general and for monitoring
      fermentation processes for the production of antibiotics and other biochemicals.

PMID- 19381374
TI  - UV dosimeter based on dichloroindophenol and tin(IV) oxide.
AB  - A UVB specific dosimeter is described comprising: a redox dye (2,6
      dichloroindophenol, DCIP), a semiconductor (tin(IV) oxide, SnO(2)) and a
      sacrificial electron donor (glycerol) dispersed in a polymer (hydroxy ethyl
      cellulose, HEC) film. The dosimeter is blue in the absence of UVB light but
      rapidly loses colour on exposure to UVB light. The spectral characteristics of a
      typical UVB dosimeter film and the mechanism by which the colour change occurs
      are detailed. DCIP UVB dosimeter films exhibit a response that is related to the
      irradiance level and duration of UVB exposure, the level of SnO(2) present and to
      a lesser extent the level of glycerol present. The response of the dosimeter
      appears to be independent of dye concentration and film thickness. Furthermore,
      DCIP UVB dosimeter films respond to solar simulated light, exhibiting a colour
      loss that can be simply related to the Minimal Erythemal Dose (MED) exposure for
      skin type II. As a consequence, such indicators have potential for measuring
      solar radiation exposure and providing an early warning of erythema for most
      Caucasian skin (i.e. skin type II).

PMID- 19381373
TI  - Quantitative SERRS immunoassay for the detection of human PSA.
AB  - We report the first use of a commonly used ELISA colorimetric substrate as a
      SERRS marker and show how it can be used for the detection of pg ml(-1) levels of
      human prostate specific antigen (PSA) in clinical samples. The technique is
      amenable over a wide range of concentrations and lends itself to future
      multiplexing analysis.

PMID- 19381375
TI  - Enzymatic activity of surface-immobilized horseradish peroxidase confined to
      micrometer- to nanometer-scale structures in nanocapillary array membranes.
AB  - Horseradish peroxidase (HRP) was immobilized on the planar surfaces and inside
      the cylindrical nanopores of nanocapillary array membranes (NCAMs) to study how
      the enzyme-catalyzed oxidation of a fluorigenic substrate, Amplex Red (AR), to
      fluorescent resorufin by hydrogen peroxide is influenced by confinement. Because
      AR was also found to be converted to resorufin photolytically at high laser
      fluences, a modified laser-induced fluorescence protocol was developed to
      characterize the enzyme-catalyzed reaction in the absence of interference from
      the photolytic reaction. Surface-immobilized HRP was studied in two environments:
      bound to the surface of a microfluidic channel, and bound to the interior of
      cylindrical nanopores in NCAMs connecting crossed microfluidic channels. HRP was
      immobilized through reaction of solvent-accessible primary amines with the epoxy
      group of the methyl methacrylate-glycidyl methacrylate copolymer synthesized in
      either planar or annular geometries to construct the test structures for
      enzymatic activity. HRP immobilized on planar surfaces shows high activity
      (approximately 10 microM min(-1)) meaning that the copolymer membrane exhibits
      good potential for immobilizing the enzyme, especially since active structures
      are obtained in a one-step reaction. HRP was also immobilized inside nanopores
      via physisorption. Enzymatic reactions inside the nanopores were characterized
      and compared to finite element simulations of a modified Eley-Rideal mechanism to
      bracket the value of the overall rate constant for the confined enzyme. Reaction
      velocities were estimated to be approximately 10-fold higher in the nanopores
      than for the same enzyme bound to a planar microfluidic surface.

PMID- 19381376
TI  - PAMAM dendrimer-enhanced DNA biosensors based on electrochemical impedance
      spectroscopy.
AB  - A novel, simple and sensitive DNA biosensor based on DNA-poly(amidoamine) (PAMAM)
      dendrimer nanoconjugates was developed by using the electrochemical impedance
      spectroscopy (EIS) technique. In this context, the assay relies on the
      hybridization of the single-stranded DNA (ssDNA) probe covalently conjugated on a
      mercaptoacetic acid self-assembled monolayer on gold electrodes, with the
      generation 4.5 (G-4.5) PAMAM-target DNA complex in solution. Once the double
      stranded DNA (dsDNA) formed on the gold electrodes, G-4.5 PAMAM bearing carboxyls
      on the periphery was anchored on the hybrids; the changes of interfacial electron
      transfer resistance (R(et)) of the electrodes were measured using an Fe(CN)(6)(3
      /4-) redox probe by electrochemical impedance spectroscopy. The results showed
      that only a complementary sequence could form a dsDNA-PAMAM with the DNA-PAMAM
      probe and give an obviously enlarged R(et) value. The non-complementary and three
      base mismatched sequence exhibited negligible impedance change compared with the
      blank measurement (the blank measurement means: ssDNA probe-modified gold
      electrode was directly measured by EIS). The unique spherical structure combining
      with more negative charges on the G-4.5 PAMAM periphery anchored on the hybrids
      could significantly amplify the hybridization signal (R(et) value), and the
      detection limit for measuring the full complementary sequence is down to pM
      level.

PMID- 19381377
TI  - Direct analysis of Stevia leaves for diterpene glycosides by desorption
      electrospray ionization mass spectrometry.
AB  - The analysis of Stevia leaves has been demonstrated without any sample
      preparation using desorption electrospray ionization (DESI) mass spectrometry.
      Direct rapid analysis was achieved using minimal amounts of sample (
      approximately 0.15 cm x 0.15 cm leaf fragment). Characteristic constituents of
      the Stevia plant are observed in both the positive and negative ion modes
      including a series of diterpene 'sweet' glycosides. The presence of the
      glycosides was confirmed via tandem mass spectrometry analysis using collision
      induced dissociation and further supported by exact mass measurements using an
      LTQ-Orbitrap. The analysis of both untreated and hexane-extracted dry leaves
      proved that DESI can be successfully used to analyze untreated leaf fragments as
      identical profiles were obtained from both types of samples. Characterization and
      semi-quantitative determination of the glycosides was achieved based on the
      glycoside profile within the full mass spectrum. In addition, the presence of
      characteristic glycosides in an all-natural commercial Stevia dietary supplement
      was confirmed. This study provides an example of the application of DESI to
      direct screening of plant materials, in this case diterpene glycosides.

PMID- 19381378
TI  - Photonic crystal borax competitive binding carbohydrate sensing motif.
AB  - We developed a photonic crystal sensing method for diol containing species such
      as carbohydrates based on a poly(vinyl alcohol) (PVA) hydrogel containing an
      embedded crystalline colloidal array (CCA). The polymerized CCA (PCCA) diffracts
      visible light. We show that in the presence of borax the diffraction wavelength
      shifts as the concentration of glucose changes. The diffraction shifts result
      from the competitive binding of glucose to borate, which reduces the
      concentration of borate bound to the PVA diols.

PMID- 19381379
TI  - Selective detection of hexachromium ions by localized surface plasmon resonance
      measurements using gold nanoparticles/chitosan composite interfaces.
AB  - Selective removal of hexavalent chromium ions from aqueous solutions using a
      chitosan/gold nanoparticles composite film was demonstrated. Localized surface
      plasmon resonance (LSPR) was used to measure the interface stability and detect
      the incorporation of chromium ions over time. The effects of pH,
      ethylenediaminetetraacetic acid (EDTA), and various foreign ions such as
      trivalent chromium, sodium, calcium, phosphate, sulfate and chloride on the
      adsorption of hexavalent chromium were investigated.

PMID- 19381380
TI  - Microwave-enhanced electroanalytical processes: generator-collector voltammetry
      at paired gold electrode junctions.
AB  - Generator-collector electrode systems allow redox processes and reaction
      intermediates from multi-step electrode reactions to be monitored. Analytically,
      collector electrode current responses are insightful and highly sensitive due to
      (i) the absence of capacitive current components and (ii) an enhanced current
      response due to 'feedback' between generator and collector electrode. Here, a
      symmetric gold-gold junction grown by controlled electro-deposition is employed
      for generator-collector voltammetry in conjunction with microwave activation.
      Three redox systems are investigated in aqueous 0.1 M KOH: (i) the reduction of
      Fe(CN)(6)(3)(-), (ii) the reduction of chloramphenicol, and (iii) the reduction
      of oxygen. Microwave radiation, when focused into the electrode-solution
      interfacial zone, causes locally enhanced temperatures with electrode surface
      temperatures reaching up to typically 380 K (estimated from the shift in the
      Fe(CN)(6)(3)(-/4)(-) equilibrium potential, at both gold electrodes). The
      resulting increase in the rate of diffusion and the onset of convection result in
      non-linear Arrhenius limiting current characteristics and in an increase in
      collection efficiency with microwave power. The gold electrode junction geometry
      allows diffusion effects (which increase the feedback current within the gap) to
      dominate over convection effects (which suppress the feedback current).

PMID- 19381381
TI  - Development of a voltammetric technique for monitoring brain dopamine metabolism:
      compensation for interference caused by DOPAC electrogenerated during
      homovanillic acid detection.
AB  - The established stability of carbon-paste electrodes (CPEs) in brain
      extracellular fluid was exploited to develop a voltammetric technique to monitor
      the dopamine metabolite, homovanillic acid (HVA), at 10 s intervals. At the scan
      rates needed for this time resolution, 3,4-dihydroxyphenylacetic acid (DOPAC),
      electrogenerated as a result of HVA oxidation, was observed in the cyclic
      staircase voltammograms, and this interfered with the straightforward reliable
      quantification of HVA. However, correction of the HVA signal, recorded in
      mixtures, with currents from the DOPAC and ascorbate regions of the voltammogram
      allowed the reproducible construction of well behaved HVA calibration plots.
      These showed good linearity, LOD values, selectivity and stability during six
      days of continuous CPE exposure to a lipid medium, which served as an in-vitro
      model of CPE implantation in brain tissue for future applications.

PMID- 19381382
TI  - Electrochemical competitive hybridization assay for DNA detection using osmium
      tetroxide-labelled signalling strands.
AB  - In this report, we present sequence-specific DNA detection by means of a
      competitive hybridization assay with osmium tetroxide-labelled signalling
      strands. The labelling of the signalling strands has been performed using
      protective strands to preserve the recognition site of these single strands for
      hybridization with the immobilized capture probes. At optimized measuring
      conditions and especially assay temperature, we could detect the presence of 25
      nM target DNA within 30 minutes, whereas the non-complementary target sequence
      did not yield any signal. The latter was observed as a decrease in square-wave
      voltammetric response of the signalling probes. Single base mismatches could be
      detected at a stringent 35 degrees C electrolyte temperature. Moreover, the
      concentration dependency of the signal was investigated. A time-consuming
      labelling procedure of the target, as typically used before, is not necessary.
      Upon application of the new protocol, there is no need for handling osmium(VIII)
      compounds during sample treatment. The signalling strands containing Os(VI) are
      prepared separately and can be stored over several months.

PMID- 19381383
TI  - Design of liposome-based pH sensitive nanoSPIN probes: nano-sized particles with
      incorporated nitroxides.
AB  - Liposome-based nanoSized Particles with Incorporated Nitroxides, or nanoSPINs,
      were designed for EPR applications as pH probes in biological systems.
      Phospholipid membrane of the liposomes with incorporated gramicidin A showed
      selective permeability to a small analyte, H(+), while protecting entrapped
      sensing nitroxide from biological reductants. An application of the pH-sensitive
      nanoSPIN in an ischemia model in rat heart homogenate allows for monitoring
      ischemia-induced acidosis while protecting encapsulated nitroxide against
      bioreduction.

PMID- 19381384
TI  - Principles of detecting vaporous thiols using liquid crystals and metal ion
      microarrays.
AB  - In this article, we show that the optical texture of a layer of liquid crystal 4
      cyano-4'-pentylbiphenyl (5CB) supported on a thiol-sensitive layer can be applied
      to detect 1-octanethiol and other vaporous thiols with high specificity. As
      demonstrated in our ellipsometry and XPS results, a thiol-sensitive layer
      comprising an array of copper ions is capable of oxidizing thiols to disulfides
      and immobilizing them on the surface. Because of the hydrophobic hydrocarbon
      chain of 1-octanethiol, the immobilization of 1-octanethiol lowers the surface
      energy. Thus, after a thin layer of 5CB is supported on the surface, the lower
      surface energy causes 5CB to adopt different orientations in regions where copper
      ions were deposited. Because 5CB is a birefringent material, different
      orientations of 5CB also result in distinct optical textures, which are visible
      to the naked eye under a pair of polarizers. Interestingly, 5CB supported on
      copper ions only responds to longer and less volatile thiols such as 1
      octanethiol, 1-hexanethiol and 1-butanethiol, but it did not respond to shorter
      and more volatile thiols such as ethanethiol. The system also shows no response
      to water and other volatile organic compounds such as acetone, ethanol, heptanol
      and heptane.

PMID- 19381385
TI  - An optimized buffer system for NMR-based urinary metabonomics with effective pH
      control, chemical shift consistency and dilution minimization.
AB  - NMR-based metabonomics has been widely employed to understand the stressor
      induced perturbations to mammalian metabolism. However, inter-sample chemical
      shift variations for metabolites remain an outstanding problem for effective data
      mining. In this work, we systematically investigated the effects of pH and ionic
      strength on the chemical shifts for a mixture of 9 urinary metabolites. We found
      that the chemical shifts were decreased with the rise of pH but increased with
      the increase of ionic strength, which probably resulted from the pH- and ionic
      strength-induced alteration to the ionization equilibrium for the function
      groups. We also found that the chemical shift variations for most metabolites
      were reduced to less than 0.004 ppm when the pH was 7.1-7.7 and the salt
      concentration was less than 0.15 M. Based on subsequent optimization to minimize
      chemical shift variation, sample dilution and maximize the signal-to-noise ratio,
      we proposed a new buffer system consisting of K(2)HPO(4) and NaH(2)PO(4) (pH 7.4,
      1.5 M) with buffer-urine volume ratio of 1 : 10 for human urinary metabonomic
      studies; we suggest that the chemical shifts for the proton signals of citrate
      and aromatic signals of histidine be corrected prior to multivariate data
      analysis especially when high resolution data were employed. Based on these, an
      optimized sample preparation method has been developed for NMR-based urinary
      metabonomic studies.

PMID- 19381386
TI  - High performance immunoassay using immobilized enzyme in nanoporous carbon.
AB  - A highly stable immunoassay format was constructed using signal-generating enzyme
      immobilized in nanoporous carbon. A mesocellular carbon foam, called MSU-F-C, was
      loaded with horseradish peroxidase (HRP), followed by cross-linking of the enzyme
      using glutaraldehyde (GA) and modification of the surface with anti-human IgG
      through EDC/sulfo-NHS chemistry. The resulting MSU-F-C/HRP/anti-human IgG stably
      retained immobilized enzymes and antibodies, showing higher thermal stability.
      The MSU-F-C/HRP/anti-human IgG retained about 80 % of initial enzyme activity at
      40 degrees C after a 5 h incubation, while the HRP/anti-human IgG conjugate
      resulted in almost 90% loss of initial activity in the same condition. In bead
      based immunoassays, the signal amplification using MSU-F-C/HRP/anti-human IgG
      enabled the sensitive colorimetric detection of a target analyte, human IgG, in a
      detection limit of approximately 33 pM, with negligible cross-reactivity against
      rabbit and chicken IgGs.

PMID- 19381387
TI  - An ultra-sensitive nanoarray chip based on single-molecule sandwich immunoassay
      and TIRFM for protein detection in biologic fluids.
AB  - This paper describes a single-molecule sandwich immunoassay method that utilizes
      total internal reflection fluorescence microscopy (TIRFM) at the single-molecule
      level for nanoarray protein chip applications. Nanoarray patterning of a biotin
      probe with a spot diameter of 179 +/- 1 nm was performed successfully on a (3
      mercaptopropyl)trimethoxysilane (MPTMS)-coated glass substrate by atomic force
      microscopy (AFM). The formation of biotin patterns was confirmed directly by
      observing the heights of bound streptavidin and biotin-antibody on glass
      substrates using an AFM in contact mode. Target protein molecules (or antigen) at
      the zepto-molar (zM) concentration level (x 10(-21) M) were detected on MPTMS
      coated glass nanoarray protein chips by TIRFM. Finally, cytokine clinical samples
      (i.e. TNF-alpha and IL-1alpha) as cancer marker protein molecules were applied to
      nanoarray protein chips, and detection limits were at 600 zM.

PMID- 19381388
TI  - A new PCR-based bioassay strategy for the detection of type A trichothecenes in
      food.
AB  - Type A trichothecenes (primarily T-2 and HT-2 toxins) are common fungal
      metabolites found in a wide range of grains and other field crops grown in
      temperate climatic zones. By acting as potent inhibitors of protein synthesis, T
      2 and HT-2 exert adverse effects particularly against rapidly proliferating
      tissues, including the bone marrow, the immune system and epithelial cells. Based
      on toxicity studies in laboratory and farm animals, a temporary tolerable daily
      intake for the sum of T-2 and HT-2 has been issued in the European Union.
      However, exposure assessments suggest that the combined intake of these natural
      compounds exceeds in many cases the proposed threshold. To further protect the
      consumers, it is therefore necessary to screen a large number of food samples for
      parts per billion levels of both T-2 and HT-2. Towards that goal, we are the
      first to report that these two type A trichothecenes induce fast and high
      amplitude transcriptional changes in cultured human breast cancer cells. This
      specific response involving marker gene inductions by more than 1000-fold has
      been exploited to develop a real-time PCR-based screening method that displays a
      limit of detection of 5 ng g(-1) for T-2 and 10 ng g(-1) for HT-2. The
      practicability of this bioassay is demonstrated by its application to the
      detection of type A trichothecenes in different food matrices.

PMID- 19381389
TI  - Sputter-induced chemical transformation in oxoanions by combination of C(60)(+)
      and Ar(+) ion beams analyzed with X-ray photoelectron spectrometry.
AB  - The change of the chemical states of inorganic oxoanion salts by low-energy
      single atomic projectiles (0.5 kV Ar(+)), high-energy cluster ion beams (10 kV
      C(60)(+)), and mixed 0.2 kV Ar(+) and 10 kV C(60)(+) are presented. Although the
      sputtering conditions of C(60)(+) and C(60)(+)-Ar(+) mixed sputtering used in
      this work provide more accurate results for profiling organic films than Ar(+)
      sputtering, the difference in profiling inorganic materials is not as dramatic.
      For inert oxoanions like carbonate and phosphate, both Ar(+) and C(60)(+)
      sputtering cause unappreciable sputter-induced chemical transformation to the
      remaining surface. For reactive oxoanions like nitrate, perchlorate, chlorate,
      and chlorite, although C(60)(+) yields slightly better results than Ar(+)
      sputtering due to the thinner disturbed layer, all the ion beams altered the
      chemical state significantly. As a result, none of these techniques can be used
      to provide true information below the surface. For intermediate oxoanions like
      nitrite and thio-S in thiosulfate, C(60)(+) yields slightly better results than
      Ar(+) sputtering. However, for sulfonate and the core-S in thiosulfate, C(60)(+)
      causes more sputter-induced chemical transformation than Ar(+) sputtering.

PMID- 19381390
TI  - A DNA biosensor based on a morpholino oligomer coated indium-tin oxide electrode
      and a cationic redox polymer.
AB  - A simple and ultrasensitive electrochemical biosensor employing a morpholino
      oligomer as capture probe and a cationic redox polymer as signal generator for
      direct detection of DNA is presented in this report. It is based on the
      immobilization of the morpholino oligomer on an indium-tin oxide (ITO) electrode
      and amperometric detection of target DNA by forming a DNA/cationic redox polymer
      bilayer on the ITO electrode. After hybridizing the morpholino capture probe
      (MCP) to the target DNA, the cationic redox polymer was introduced to the ITO
      electrode via electrostatic interaction with the hybridized DNA. The deposited
      redox polymer exhibited excellent electrocatalytic activity towards the oxidation
      of ascorbic acid (AA), allowing for direct voltammetric and amperometric
      detection of DNA. Under optimized experimental conditions, a detection limit of
      1.0 pM and linear current-concentration relationship up to 500 pM were obtained
      in amperometry. The resulting biosensors offered much better mismatch
      discrimination against mismatch sequences than their DNA counterparts.

PMID- 19381391
TI  - Real-time monitoring of luminescent lifetime changes of PtOEP oxygen sensing film
      with LED/photodiode-based time-domain lifetime device.
AB  - A cost-effective LED/photodiode(PD)-based time-domain luminescent lifetime
      measuring device with rugged electronics and simplified algorithms was assembled
      and successfully used to characterize oxygen sensing films, by continuously
      monitoring phosphorescence lifetime changes of phosphorescent platinum
      octaethylporphyrin (PtOEP) in cardo poly(aryl ether ketone) polymer (IMPEK-C) vs.
      variation of the oxygen partial pressure in a gas mixture (O(2)/N(2)). The
      results determined by both phosphorescence lifetime and intensity monitoring were
      compared and the lifetime mode gave results which are in good agreement with the
      intensity mode. The lifetime-based linear Stern-Volmer plot indicates that the
      PtOEP molecules are nearly homogeneously distributed in the sensing film. The
      phosphorescent lifetime of the PtOEP film changes from 75 micros in neat N(2) to
      less than 2 micros in neat O(2). The sensing system (by combination of the PtOEP
      sensing film with the home-assembled lifetime device) gives a high lifetime-based
      O(2) sensing resolution, e.g. about 2 micros Torr(-1) for low O(2) concentration
      (below 3.5% O(2), V/V). This feasible lifetime device configuration is affordable
      to most sensor laboratories and the device may facilitate the study of O(2)
      sensing material with the continuous lifetime monitoring method.

PMID- 19381392
TI  - Electrochemical genosensor for the rapid detection of GMO using loop-mediated
      isothermal amplification.
AB  - In this study, we are reporting for the first time an efficient, accurate and
      inexpensive rapid detection system which employs the integration of isothermal
      amplification and subsequent analysis of unpurified amplicons by an
      electrochemical system. In our experiments, loop-mediated isothermal
      amplification (LAMP) with its higher efficiency than PCR was performed at a
      constant temperature (65 degrees C). Amplification products were combined with a
      redox active molecule Hoechst 33258 [H33258, 2'-(4-hydroxyphenyl)-5-(4-methyl-1
      piperazinyl)-2,5'-bi(1H-benzimidazole)] and analyzed by a DNA stick (DS) which is
      integrated with a disposable electrochemical printed (DEP) chip using linear
      sweep voltammetry (LSV). The DNA minor groove binding of the H33258 molecule
      causes a significant drop in the peak current intensity of the H33258 oxidation.
      The phenomenon of DNA binding induced by H33258, in addition to changes in the
      anodic current peak, was used to detect maize CBH 351 variety (StarLink). Since
      laborious probe immobilization was not required, and amplification and detection
      were performed on a single device, our biosensor eliminates potential cross
      contamination. We believe that this type of sensor will have an unprecedented
      impact for environmental protection.

PMID- 19381393
TI  - Determination of total bile acid levels using a thick-film screen-printed Ir/C
      sensor for the detection of liver disease.
AB  - An electrochemical sensor, based on thick-film screen-printed Ir/C working and
      counter electrodes, was developed for the detection of total bile acid
      concentration in a physiological fluid for potential patient management in
      patients with liver disease. Current electrochemical methods of detecting total
      bile acid levels involve the use of potentials greater than +0.45 V, versus an
      Ag/AgCl reference electrode, and require a selectively permeable membrane. The
      proposed detection method did not require any membrane and used a potential of
      +0.27 V versus Ag/AgCl. This biosensor used 3-alpha-hydroxysteroid dehydrogenase
      (3alpha-HSD) (EC 1.1.1.50) immobilized on the thick-film screen-printed working
      electrode to detect the enzymatically generated NADH. The production of the NADH
      resulted from the reaction of the enzyme with bile acids such as sodium cholate,
      taurocholic and taurochenodeoxycholic acid, which could then be used to quantify
      the total bile acid. Constant potential measurements showed that this biosensor
      had good linear performance over a 0-200 microM concentration range in the
      phosphate buffer and the bovine serum. The sensor performance was also examined
      at different temperatures and pH conditions. This sensor prototype could be used
      for single use, disposable detection of total bile acids, extending its
      applicability for simple and early detection of liver disease.

PMID- 19381394
TI  - Multiple sized europium(III) chelate-dyed polystyrene particles as donors in FRET
      - an application for sensitive protein quantification utilizing competitive
      adsorption.
AB  - A variety of particles have been adopted as solid support in bioaffinity assays,
      and the ability to modify the particle properties makes them a versatile tool in
      assay development. In separation-free fluorescence resonance energy transfer
      (FRET) assays, fluorescent particles have been used as donors and acceptors due
      to their high binding capacity and high specific activity. The availability of
      multiple fluorophores within the FRET range renders the orientation of individual
      donors and acceptors a non-factor enabling efficient sensitization. The high
      specific activity, being proportional to the particle size, may also inflict
      background fluorescence due to distance dependency of FRET, if the donor emission
      and detection wavelengths overlap. This is the first study to evaluate the impact
      of differently sized (47, 68, 92 and 202 nm in diameter) europium(III) chelate
      doped polystyrene/acrylic acid donor particles on the core-related background
      fluorescence in a separation-free FRET-based assay utilizing competitive
      adsorption of acceptor-labelled protein. Within the particle size range studied,
      the particle core size-related background fluorescence showed no significant
      effect on the assay performance at the detection wavelength, which was selected
      on account of donor emission minimum. The assay sensitivity and dynamics showed
      compliancy with the rules of competitive assay. The results can be used in
      designing a competitive separation-free FRET-based assay utilizing particles as
      donors. In accordance, we applied the method for protein quantification. Sample
      protein prevented the adsorption of acceptor-labelled protein on the nanoparticle
      reducing energy transfer. Using this approach, a 100- to 1000-fold lower protein
      concentration was measured in comparison to traditional photometric protein
      assays suggesting that a high sensitivity assay can be constructed using FRET
      based nanoparticle assay concepts.

PMID- 19381396
TI  - Sol-gel derived nano-structured zinc oxide film for sexually transmitted disease
      sensor.
AB  - A 20-mer thiolated oligonucleotide probe (th-ssDNA) specific to Neisseria
      gonorrhoeae immobilized onto a sol-gel derived nano-structured zinc oxide (ZnO)
      film dip-coated onto an indium-tin-oxide (ITO) glass substrate has been used for
      the fabrication of a DNA biosensor for sexually transmitted disease (gonorrhoea)
      detection using hybridization technique. The results of characterization studies
      carried out on this th-ssDNA-ZnO/ITO bioelectrode using X-ray diffraction, UV
      Visible, Fourier-transform infrared, scanning electron microscopy and
      electrochemical techniques reveal the linearity as 0.000524 fmol-0.524 nmol, with
      a detection limit of 0.000704 fmol within 60 s.

PMID- 19381395
TI  - Renewable surface fluorescence sandwich immunoassay biosensor for rapid sensitive
      botulinum toxin detection in an automated fluidic format.
AB  - A renewable surface biosensor for rapid detection of botulinum neurotoxin
      serotype A is described based on fluidic automation of a fluorescence sandwich
      immunoassay, using a recombinant protein fragment of the toxin heavy chain (
      approximately 50 kDa) as a structurally valid simulant. Monoclonal antibodies AR4
      and RAZ1 bind to separate non-overlapping epitopes of the full botulinum
      holotoxin ( approximately 150 kDa). Both of the targeted epitopes are located on
      the recombinant fragment. The AR4 antibody was covalently bound to Sepharose
      beads and used as the capture antibody. A rotating rod flow cell was used to
      capture these beads delivered as a suspension by a sequential injection flow
      system, creating a 3.6 microL column. After perfusing the bead column with sample
      and washing away the matrix, the column was perfused with Alexa 647 dye-labeled
      RAZ1 antibody as the reporter. Optical fibers coupled to the rotating rod flow
      cell at a 90 degrees angle to one another delivered excitation light from a HeNe
      laser (633 nm) using one fiber and collected fluorescent emission light for
      detection with the other. After each measurement, the used Sepharose beads are
      released and replaced with fresh beads. In a rapid screening approach to sample
      analysis, the toxin simulant was detected to concentrations of 10 pM in less than
      20 minutes using this system.

PMID- 19381398
TI  - The transition metal hexafluorides.
AB  - The nine transition metal hexafluorides present a unique series of closely
      related compounds. Deviations from octahedral structures are influenced by Jahn
      Teller effects and spin orbit coupling. The most pronounced chemical behaviour is
      the increasing electron affinity in the direction WF(6)--> PtF(6) and MoF(6)-->
      RuF(6), so that with PtF(6) and RuF(6) values of 7 eV or higher are reached. All
      hexafluorides can be used as one electron oxidants, starting with mild (WF(6)) up
      to extreme (PtF(6), RuF(6)) oxidation power.

PMID- 19381397
TI  - Novel fluorescence enhancement IgE assay using a DNA aptamer.
AB  - In this paper, we demonstrate a fluorescence immunoglobulin E (IgE) assay probe
      based on a DNA aptamer. A Texas red-labeled short DNA strand (T-DNA)
      complementary with part of the IgE aptamer sequence was used to produce the
      fluorescence enhancement effected upon the binding of IgE to the aptamer. Another
      short DNA strand labeled with dabcyl quencher (Q-DNA) complementary with part of
      the aptamer sequence nearby the T-DNA location was used to lower the background
      fluorescence. The IgE can be detected in the concentration range from 9.2 x 10(
      11) to 3.7 x 10(-8) mol L(-1) with a detection limit of 5.7 x 10(-11) mol L(-1).

PMID- 19381399
TI  - Iridium tricarbido complexes via transmetallation with tricarbidomercurials.
AB  - The reactions of Vaska's complex with [Hg{C[triple bond]CC[triple
      bond]W(CO)(2)(L)}(2)] (L = HB(pz)(3), HB(pzMe(2))(3), pz = pyrazol-1-yl)
      unexpectedly provide the structurally characterized tetrametallic trans
      bis(tricarbido)complex [Ir(HgCl){C[triple bond]CC[triple
      bond]W(CO)(2)(L)}(2)(CO)(PPh(3))(2)].

PMID- 19381400
TI  - Molecular and supramolecular Ni(II) wheels from alpha-benzoin oxime.
AB  - The use of alpha-benzoin oxime in Ni(II) chemistry leads to the formation of a
      family of unusual molecular and supramolecular wheels.

PMID- 19381401
TI  - Electrochemistry of ruthenium(II) complexes of 8-aminoquinoline.
AB  - Oxidation of [Ru(NH(2)Q)(3)](2+) (NH(2)Q = 8-aminoquinoline) results in
      intermolecular coupling of 8-aminoquinoline ligands to yield an electroactive
      polymer. Oxidative polymerization is not observed for [Ru(bpy)(2)(NH(2)Q)](2+)
      (bpy = 2,2'-bipyridine), where only one 8-aminoquinoline ligand is present.

PMID- 19381402
TI  - Enhancement in electrochemical catalytic activity of mesoporous RuO(x)H(y) and
      Pt/RuO(x)H(y) by gas treatment.
AB  - A well-crystallized mesoporous hydrous ruthenium dioxide (RuO(x)H(y)) with high
      surface area of 120 m(2) g(-1) and high electrochemical catalytic activity has
      been synthesized by a replicating route with the mesoporous silica (KIT-6) as
      hard template. The materials were characterized by means of thermo-gravimetric
      analysis (TG), X-ray diffraction (XRD), field emission scanning electron
      microscopy (FE-SEM), transmission electron microscopy (TEM) and N(2) sorption.
      The electrocatalytic activity of the samples for methanol oxidation were
      investigated by cyclic voltammetry (CV) and linear scan voltammetry (LSV)
      techniques. A mixed gas of CO and O(2) was adopted to investigate the effect of
      gas treatment on the electrochemical activity of the samples. The results show
      that the electrocatalytic activity of the prepared mesoporous RuO(x)H(y) and 3
      wt% Pt/mesoporous RuO(x)H(y) toward methanol oxidation was much enhanced after
      treatment with a mixed gas of CO and O(2). The enhanced electrochemical catalytic
      activity of the materials might be attributed to the structure activation during
      the gas treatment and the high surface area of RuO(x)H(y) matrix with mesoporous
      structure.

PMID- 19381403
TI  - Attempting to understand (and control) the relationship between structure and
      magnetism in an extended family of Mn(6) single-molecule magnets.
AB  - The synthesis and characterisation of a large family of hexametallic [Mn(III)(6)]
      Single-Molecule Magnets of general formula [Mn(III)(6)O(2)(R-sao)(6)(X)(2)(sol)(4
      6)] (where R = H, Me, Et; X = (-)O(2)CR' (R' = H, Me, Ph etc) or Hal(-); sol =
      EtOH, MeOH and/or H(2)O) are presented. We show how deliberate structural
      distortions of the [Mn(3)O] trinuclear moieties within the [Mn(6)] complexes are
      used to tune their magnetic properties. These findings highlight a qualitative
      magneto-structural correlation whereby the type (anti- or ferromagnetic) of each
      Mn(2) pairwise magnetic exchange is dominated by the magnitude of each individual
      Mn-N-O-Mn torsion angle. The observation of magneto-structural correlations on
      such large polymetallic complexes is rare and represents one of the largest
      studies of this kind.

PMID- 19381404
TI  - Novel diazaphospholidine terminated polyhedral oligomeric silsesquioxanes in
      styrene and vinyl acetate hydroformylation: synthesis and molecular dynamics
      studies.
AB  - New diazaphospholidine POSS macromolecules have been synthesised and tested in
      styrene and vinyl acetate hydroformylation. Whilst some of them have shown
      activity, others precipitated upon mixing with the rhodium precursor preventing
      its efficient use. Molecular dynamics has been used to help understand these
      observations. Rigid and compact dendritic structures with phosphine groups
      engineered to have low mobility but high probability of sitting at distances
      favouring bidentate coordination with the rhodium precursors are necessary for
      the macromolecular ligands to be active. More flexible structures having lower
      probability of phosphine separations suitable for bidentate complex formation are
      more prone to form oligomeric dendritic species and hence to crosslink the
      macromolecules and precipitate.

PMID- 19381406
TI  - Platinum complexes having redox-active PPh2C[triple bond]CFc and/or C[triple
      bond]CFc as terminal or bridging ligands.
AB  - A series of heteronuclear-Pt(ii) complexes containing ferrocenylethynyl units
      linked directly (Pt-C[triple bond]CFc) or through a phosphorous atom (Pt
      PPh(2)C[triple bond]CFc) to the platinum center is reported. The reaction of
      derivative [cis-Pt(R(F))(2)(PPh(2)C[triple bond]CFc)(2)] (R(F) = C(6)F(5)) with
      the solvate complex [cis-Pt(R(F))(2)(thf)(2)] leads to the formation of an
      asymmetrical heteronuclear diplatinum complex [{Pt(R(F))(2)(mu-1kappaP:2eta(2)
      PPh(2)C[triple bond]CFc)(2)}Pt(R(F))(2)] having the "cis-Pt(R(F))(2)" fragment
      coordinated to the triple bonds of both ferrocenylethynylphosphine units, while
      treatment of [cis-Pt(C[triple bond]CFc)(2)(PPh(2)C[triple bond]CR)(2)] (R = Fc ,
      Ph , tBu ) with the same solvate [cis-Pt(R(F))(2)(thf)(2)], affords double
      ferrocenylacetylide-bridged diplatinum systems [{Pt(PPh(2)C[triple bond]CR)(2)(mu
      eta(1):eta(2)-C[triple bond]CFc)(2)}Pt(R(F))(2)] . The solid-state structures of
      [cis/trans-Pt(R(F))(2)(PPh(2)C[triple bond]CFc)(2)] /, [cis
      Pt(R(F))(2)(PPh(2)C[triple bond]CFc)(tht)] (tht = tetrahydrothiophene),
      [{Pt(R(F))(2)(mu-1kappaP:2eta(2)-PPh(2)C[triple bond]CFc)(2)}Pt(R(F))(2)] and
      [{Pt(PPh(2)C[triple bond]CtBu)(2)(mu-eta(1):eta(2)-C[triple
      bond]CFc)(2)}Pt(R(F))(2)] have been determined by X-ray diffraction methods. The
      electronic spectra and the electrochemical behaviour of all monoplatinum
      derivatives are discussed, showing a different extent of interaction between the
      remote ferrocenyl groups when they belong to PPh(2)C[triple bond]CFc or C[triple
      bond]CFc ligands. For the diplatinum systems and , containing bridging
      (kappaP:eta(2)-PPh(2)C[triple bond]CFc ) or (eta(1):eta(2)-C[triple bond, length
      as m-dash]CFc ) ligands, their electrochemical properties were also compared with
      the parent precursors.

PMID- 19381405
TI  - Stepwise addition of CuNCS onto [Et(4)N][Tp*WS(3)]: design, syntheses, structures
      and third-order nonlinear optical properties.
AB  - Stepwise reactions of [Et(4)N][Tp*WS(3)] () (Tp* = hydridotris(3,5
      dimethylpyrazol-1-yl)borate) with 1-4 equiv. of CuNCS (and Et(4)NBr in the case
      of three equiv. of CuNCS) afforded the [1 + 1] to [1 + 4] addition products
      [Et(4)N][Tp*WS(mu-S)(2)(CuNCS)].0.5CH(2)Cl(2) (.0.5CH(2)Cl(2)),
      [Et(4)N][Tp*W(mu(3)-S)(mu-S)(2)(CuNCS)(2)].ClCH(2)CH(2)Cl (.ClCH(2)CH(2)Cl),
      [Et(4)N](2)[Tp*W(mu(3)-S)(3)(CuNCS)(3)(mu(3)-Br)].1.5aniline (.1.5aniline), and
      {[Et(4)N][Tp*W(mu(3)-S)(3)(Cu-mu-SCN)(3)(Cu-mu(3)-NCS)]}(n) (). Compounds were
      characterized by elemental analysis, IR spectra, UV-vis spectra, (1)H NMR, and
      single-crystal X-ray crystallography. The cluster anion of contains a [WS(2)Cu]
      core formed by addition of one CuNCS group onto the [Tp*WS(3)] species. The
      cluster anion of has a butterfly-shaped [WS(3)Cu(2)] core constructed by addition
      of two CuNCS groups onto the [Tp*WS(3)] species. The cluster dianion of consists
      of a cubane-like [Tp*WS(3)Cu(3)(mu(3)-Br)] core assembled by addition of three
      CuNCS groups onto the [Tp*WS(3)] species followed by filling a mu(3)-Br into the
      void of the incomplete cubane-like [Tp*WS(3)(CuNCS)(3)] fragment. has a 2D
      cluster-supported layer network in which each [Tp*WS(3)Cu(3)] core acting as a
      pyramidal 3-connecting node interconnects with the [Cu(NCS)(4)] units through
      thiocyanate bridges. In addition, the third-order nonlinear optical (NLO)
      performances of in DMF were also investigated by Z-scan techniques.

PMID- 19381407
TI  - Five related metal-organic frameworks constructed from [Ln2(SO4)2(H2O)n]2+ units
      and oxalate or acetate ligands.
AB  - We have synthesized a series of lanthanide-based metal-organic solids and
      characterized them through structural, magnetic and luminescence analyses. The
      nine compounds in the series NH(4)[Ln(SO(4))(H(2)O)(C(2)O(4))] [Ln = Ce, Nd, Eu,
      Gd (x2), Tb, Dy, Er, Yb] belong to four new three-dimensional (3D) structural
      groups, which we label CKMOF-4a, -4b, -5a, and -5b. The CKMOF-4a (Ce.) and -4b
      (Gd., Tb., Dy., Er., Yb.) structures feature [Ln(2)(SO(4))(2)(H(2)O)(2)](2+)
      units and C(2)O(4)(2-) ligands having the same symmetry operations, but their
      SO(4)(2-) anions feature different connective modes. These units are extended
      into one-dimensional ribbons fused together by oxalate ligands to form the two 3D
      open frameworks. The structures of CKMOF-5a (Nd.) and -5b (Eu., Gd.) comprise
      networks of c-glide-arranged [Ln(2)(SO(4))(2)(H(2)O)(2)](2+) units, in which the
      oxalate ligands are encapsulated within eight-membered rings. The networks are
      supported by distinct sites of oxalate ligands to form the two types of 3D open
      frameworks, the structural topologies of which are distinguished by the versatile
      connective modes of the SO(4)(2-) anions. The polymeric phases CKMOF-4b and -5b
      exist in the Gd analogues. For the Dy analogues, varying the size of the cation
      used as the template led to the selective precipitation of each of these two
      phases. The layer structure of [Gd(SO(4))(H(2)O)(2)(CH(3)CO(2))] (Gd.), labelled
      CKMOF-6, assembled from [Gd(2)(SO(4))(2)(H(2)O)(4)](2+) units and acetate
      ligands; the geometries of the [Gd(2)O(2)] rhombic units may induce ferromagnetic
      coupling at low temperature. Eu. and Tb. were luminescent, displaying red and
      green emissions, respectively.

PMID- 19381408
TI  - Influence of amine ligands on the aquation and cytotoxicity of trans-diamine
      platinum(II) anticancer complexes.
AB  - Three (15)N-labelled trans-Pt(ii) amine complexes with isopropylamine ((15)N
      ipa), methylamine ((15)N-ma) and dimethylamine ((15)N-dma) have been prepared and
      characterized. 2D [(1)H,(15)N] HSQC NMR spectroscopy was used to obtain the rate
      and equilibrium constants for the aquation of trans-[PtCl(2)((15)N-ipa)((15)N
      ma)] ((15)N-1), trans-[PtCl(2)((15)N-dma)((15)N-ma)] ((15)N-2) and trans
      [PtCl(2)((15)N-dma)((15)N-ipa)] ((15)N-) in 100 mM NaClO(4) solutions at 298 K.
      New (15)N shift ranges for H(2)N-Pt(II)-N and HN-Pt(II)-N groups are reported.
      Formation of the diaqua complex was not observed for and accounted for <2% of the
      species at equilibrium for 1 and 2 . The first aquation step is significantly
      faster for 2 (k(1) = 14 x 10(-5) s(-1)) than for the two complexes with the
      bulkier ipa ligand (k(1) = 5.5 x 10(-5) s(-1) (), 6.1 x 10(-5) s(-1) (3)), but 2
      is the least aquated of the three complexes at equilibrium. The pK(a) values for
      the monoaqua adducts of 1-3 are similar (5.98, 5.85 and 5.91, respectively) and
      0.4 pH units lower than the related cis complex cis-[PtCl(2)(dma)(2)], indicating
      a smaller proportion of more reactive aqua species will exist at physiological
      pH. The pK(a) values for the diaqua adduct of 2 (4.59 and 7.98) are 0.3-0.6 pH
      units higher than those of 1(4.31 and 7.30) and 3 (4.28 and 7.29), which have
      very similar values. The speciation profiles of 1-3 , calculated on the basis of
      the calculated equilibrium and dissociation constants, indicate that <1%
      hydrolyzed species will exist under physiological conditions in cancer cells. The
      cytotoxicity of 1-3 (non-(15)N-labelled) was assessed in three cancer lines
      (SF268, MCF-7 and NCI-H460). The new trans-Pt(ii) diamine complex 2 is more
      active than 1 and 3 in all cases and is more potent than cisplatin in the MCF-7
      adenocarcinoma cell line.

PMID- 19381409
TI  - Reactivity of 1,3-bis(2-pyridyl)benzene, N--CH--N, with gold(III) chlorides:
      salts, adducts and cyclometalated pincer derivatives. Crystal and molecular
      structures of [HN--CH--N][AuCl4], [Au(N--C--N)Cl][PF6] and [Au(N--C-
      N)Cl(PPh3)2][PF6].
AB  - The reaction of 1,3-bis(2-pyridyl)benzene, N--CH--N, with H[AuCl(4)] has been
      studied under different conditions. Mono- ([N--CH--NH][AuCl(4)]) and di
      protonated salts ([HN--CH--NH][AuCl(4)](2)), as well as an adduct, [(N--CH-
      N)(AuCl(3))(2)], have been isolated. Very rare cyclometalated pincer derivatives,
      [Au(N--C--N)Cl](+) have been obtained as different salts, either by
      transmetallation from the corresponding mercury(ii) derivative, [Hg(N--C--N)Cl],
      or by direct C-H activation. The structures in the solid state of [N--CH-
      NH][AuCl(4)] and [Au(N--C--N)Cl][PF(6)] have been solved by X-ray diffraction.
      Reaction of the pincer derivatives with PPh(3), dppm
      (bis(diphenylphosphino)methane) and dppe (1,2-bis(diphenylphosphino)ethane)
      occurs with displacement of the coordinated nitrogen atoms to afford [Au(N--C-
      N)(Cl)(PPh(3))(2)](+), [Au(N--C--N)(Cl)(dppm)(2)](+) and [Au(N--C-
      N)(Cl)(dppe)](+), respectively. The X-ray structure of [Au(N--C-
      N)(Cl)(PPh(3))(2)][PF(6)] confirms that the ligand N--C--N is only sigma-carbon
      bonded and the PPh(3) molecules are in a trans-arrangement. The pattern of the
      (31)P{(1)H}NMR spectrum of [Au(N--C--N)(Cl)(dppm)(2)](+), a pair of "triplets",
      deserves comments: the spectrum is not of the A(2)X(2) type but a case of a
      deceptively simple AA'XX' spin system.

PMID- 19381410
TI  - Synthesis and crystal structure of pentavalent uranyl complexes. The remarkable
      stability of U O2X (X = I, SO3CF3) in non-aqueous solutions.
AB  - The reaction of [UO(2)I(2)(THF)3] with KC(5)R(5) (R = H, Me) or K(2)C(8)H(8) in
      pyridine gave crystals of [{UO(2)(py)(5)}{KI2(py)2}]. (1), which were desolvated
      under vacuum into pulverulent [UO(2)(py)2.2KI2] (2).Similar reactions with
      [UO2(OTf)2] afforded [UO2(py)2.3K(OTf)2] (3) as a powder and crystals of
      [{UO(2)(py)(5)}2{K(3)(OTf)(5)}. py]. (4.py), which were also obtained together
      with crystals of [{UO2(py)5}2{K(OTf)2(py)2}][OTf] py (5. py) by treating
      [UO2(OTf)2] with KC(4)Me(4)P. Crystals of 6. py, the thallium analogue of 5. py,
      were isolated from the reaction of [UO2(OTf)2] and TlC5H5. Treatment
      of[UO2I2(THF)3] with LiCH2SiMe3 in pyridine afforded crystals of
      [{UO(2)(py)5}{LiI(py)2}][I] (7) while[UO(2)(OTf)2] reacted with the alkyllithium
      reagent in acetonitrile to give crystals of [{UO2(py)5}{Li2(OTf)3}]. (8) in
      pyridine. The crystal structures of 1, 4. py, 5. py, 6. py, 7 and 8 revealed the
      presence of U=O-->M interactions (M = Li, K, Tl), and the rich diversity of these
      structures, from dinuclear (7) to 3D polymeric (4), is related to the distinct
      coordination numbers of the M+ ion and ligation modes of the bridging iodide and
      triflate ligands as well as the presence of U=O-->M interactions. The mononuclear
      complexes [UO2(OTf)(THF)n] (9) and [UO2(OTf)(Et2O)0.5] (10) were respectively
      obtained by reaction of [UO2(OTf)2] with KC5R5 in THF or LiCH2SiMe3 in Et2O, and
      were transformed into [UO(2)(OTf)(py)2] (11) in pyridine. Treatment of
      [UO(2)I(2)(THF)3] with TlC5H5 inpyridine afforded crystals of [UO2(py)5][I]. py
      (12. py) which were desolvated under vacuum into the powder of [UO(2)I(py)2.5]
      (14). The same reaction in THF gave [UO2I(THF)2.7] (13) in powder form.Crystals
      of [UO(2)(CyMe4BTBP)(py)][OTf]. 1.5py (15. 1.5py) and the powder of
      [UO2I(CyMe4BTBP)](16) were obtained by treating [UO(2)(CyMeBTBP)X2] (X= OTf, I)
      with KC5Me5 or TlC5H5,respectively. The uranyl(V) chloride and nitrate compounds
      [UO(2)Cl(py)3] (17) and [UO2(NO3)(py)3] (18)were prepared by reaction of the
      uranyl(VI) precursors with TlC5H5 in pyridine; complex 18 was also obtained by
      treating 13 with TlNO3. Crystals of the neutral mononuclear complex
      [UO(2)(OTf)(py)4] (19)were isolated from reaction of [UO(2)(OTf)2] with Me3SiC5H5
      in acetonitrile. Similar reaction with [UO(2)Cl(2)(THF)2]2 in pyridine gave
      crystals of [UO(2)Cl(2)(py)3]. The crystal structures of 12 py, 15. 1.5py and 19
      were determined; the structure of 15 was compared with that of the uranyl(VI)
      counterpart. All the uranyl(V) compounds are remarkably stable in pyridine
      solution; the IR absorption at 816 cm-1 is attributed to the v (asym)(U=O) of the
      ubiquitous [UO(2)(py)(5)]+ species.

PMID- 19381411
TI  - Coordination complexes with the redox active tetrathiafulvalene based imino
      pyrazine ligand: syntheses, a radical cation salt, crystal structures and
      electrochemistry.
AB  - The tetrathiafulvalene based 2-immino-pyrazine derivative (TTF-CHN-2-pyz) () was
      synthesized and characterized. Its radical cation salt ( (+)PF(6)(-)) was
      prepared as single crystals by electrocrystallisation. (+)PF(6)(-) crystallizes
      in the triclinic P1 space group. Four 1 : 2 bis(hexafluoroacetylacetonate)M(ii)
      complexes coordinated with were prepared (M = Mn for , M = Co for , M = Cu for
      and M = Zn for ). Complex crystallizes in the monoclinic C2/c space group,
      complexes and crystallize in the triclinic space group P1. Two pyrazine N atoms
      from two different donors are coordinated in cis configuration for and trans
      configuration for and to the metallic ion of M(hfac)(2) (hfac(
      )=hexafluoroacetylacetonate anion). The manganese atom adopts a pseudo-compressed
      octahedral geometry while the copper and the zinc ions adopt axially elongated
      octahedral geometries. Both crystal packing structures and electrochemical
      properties are appropriate for their potential use as starting molecular bricks
      for conducting and magnetic materials.

PMID- 19381412
TI  - Porous 2D coordination polymeric formate built up by Mn(II) linking of Fe3O
      units: influence of guest molecules on magnetic properties.
AB  - A first representative of coordination polymers, built from polynuclear
      carboxylate bridged by mononuclear carboxylate, has been synthesised and
      structurally characterized. The compound
      [{Fe(3)O(HCOO)(6)}{Mn(HCOO)(3)(H(2)O)(3)}].3.5HCOOH crystallised in the hexagonal
      system (space group P6(3)), a = b = 12.369(5) A, c = 12.992(5) A, alpha = beta =
      90 degrees , gamma = 120 degrees , V = 1721.4(12) A(3). The crystal structure is
      built from 2D layers, which are formed by the linking of trinuclear
      {Fe(3)O(HCOO)(6)}(+) units by mononuclear {Mn(HCOO)(3)(H(2)O)(3)}(-) bridges.
      These 2D honeycomb layers are connected by molecules of formic acid through a
      hydrogen bond network. The compound has the voids at the centre of the hexagons.
      These voids are filled by captured solvent molecules. Solvate molecules are also
      located between the 2D layers, linking them through a system of H-bonds. All
      these solvates can be easily removed and/or exchanged, which results in the
      formation of [{Fe(3)O(HCOO)(6)}{Mn(HCOO)(3)(H(2)O)(3)}].0.5HCOOH.H(2)O and
      [{Fe(3)O(HCOO)(6)}{Mn(HCOO)(3)(H(2)O)(3)}]. Magnetic properties of the compounds
      can be considered as the superposition of magnetism of Fe(3)O trinuclear units,
      for which magnetism is governed by the superexchange interaction between Fe(3+)
      spins (with one Fe-Fe superexchange parameter J) and the magnetism of spins of
      Mn(2+) ions, the interactions between these units can be taken into account by
      molecular field, zJ'. The destruction of the hydrogen bond network caused by
      evacuation of solvent molecules significantly modifies the overall magnetism. It
      was found that zJ' depends on the presence of solvent molecules in the structure.

PMID- 19381413
TI  - Tetranuclear group 7/8 mixed-metal and open trinuclear group 7 metal carbonyl
      clusters bearing bridging 2-mercapto-1-methylimidazole ligands.
AB  - The reactivity of group 7 metal dinuclear carbonyl complexes [M(2)(CO)(6)(mu
      SN(2)C(4)H(5))(2)] (1, M = Re; 2, M = Mn) toward group 8 metal trinuclear
      carbonyl clusters were examined. Reactions of 1 and 2 with
      [Os(3)(CO)(10)(NCMe)(2)] in refluxing benzene furnished the tetranuclear mixed
      metal clusters [Os(3)Re(CO)(13)(mu(3)-SN(2)C(4)H(5))] (3) and
      [Os(3)Mn(CO)(13)(mu(3)-SN(2)C(4)H(5))] (4), respectively. Similar treatment of 1
      and 2 with Ru(3)(CO)(12) yielded the ruthenium analogs [Ru(3)Re(CO)(13)(mu(3)
      SN(2)C(4)H(5))] (5), and [Ru(3)Mn(CO)(13)(mu(3)-SN(2)C(4)H(5))] (6), but in the
      case of 2 a secondary product [Mn(3)(CO)(10)(mu-Cl)(mu(3)-SN(2)C(4)H(5))(2)] (7)
      was also formed. Compounds have a butterfly core of four metal atoms with the M
      (Mn or Re) at a wingtip of the butterfly and containing a noncrystallographic
      mirror plane of symmetry. This result provides a potential method for the
      synthesis of a series of new group 7/8 mixed metal complexes containing a
      bifunctional heterocyclic ligand. Compound 7 is a unique example of a 54-electron
      trimanganese complex having bridging 2-mercapto-1-methylimidazolate and chloride
      ligands. Interestingly, the reaction of 1 with Fe(3)(CO)(12) at 70-75 degrees C
      furnished the tri- and dirhenium complexes [Re(3)(CO)(10)(mu-H)(mu(3)
      SN(2)C(4)H(5))(2)] (8) and [Re(2)(CO)(6)(N(2)C(4)H(5))(mu-SN(2)C(4)H(5))(2)] (9),
      respectively instead of the expected formation of the mixed-metal clusters. The
      former is an interesting example of a 52-electron trirhenium-hydridic complex
      containing bridging 2-mercapto-1-methylimidazolate ligand, while the latter can
      be viewed as a 1-methylimidazole adduct of 1 . No mixed Fe-Re complexes were
      produced in this reaction. The molecular structures of the new compounds and were
      established by single-crystal X-ray diffraction analyses and the DFT studies of
      compounds , and are reported.

PMID- 19381414
TI  - Supramolecular organoplatinum(iv) chemistry: a nanotube structure supported by
      hydrogen bonds.
AB  - The oxidative addition of 4-BrCH(2)C(6)H(4)-C(=O)NH-t-Bu to [PtMe(2)(bu(2)bipy)],
      bu(2)bipy = 4,4'-di-tert-butyl-2,2'-bipyridine, gave [PtBrMe(2)(CH(2)C(6)H(4)
      C(=O)NH-t-Bu)(bu(2)bipy)], which reacted with AgX and a bridging ligand LL to
      give binuclear complexes [{PtMe(2)(CH(2)C(6)H(4)-C(=O)NH-t-Bu)(bu(2)bipy)}(2)(mu
      LL)]X(2), LL = 1,4-pyrazine or 4,4'-bipyridine, X = BF(4) or PF(6). The complexes
      all take part in hydrogen bonding through either NHO[double bond]C, NHFB or NHFP
      interactions and, in the case with LL = 4,4'-bipyridine, X = PF(6), a
      supramolecular structure containing tubes is formed.

PMID- 19381415
TI  - Synthesis, photoelectron spectroscopy and quantum chemical study of kinetically
      unstabilized phosphines complexed by borane.
AB  - Ethynyl- and allenylphosphine-boranes have been prepared by addition at low
      temperature of borane on the free phosphine. Purification was performed by
      selective trapping in vacuo and the complexes were characterized by NMR and
      infrared spectroscopy and mass spectrometry. A kinetic stability lower than that
      of the corresponding free systems was observed. A series composed of these
      compounds and methyl-, vinyl-, allyl- and propargylphosphine-boranes was
      investigated by photoelectron spectroscopy and B3LYP/aug-cc-pVTZ quantum chemical
      study in order to define the variation in the electronic effects between the free
      systems and the corresponding complexes. Although the complexation only led to
      minor changes in the unsaturated moiety, the P-C bond shortens in all cases
      because of the charge transfer from phosphorus to boron. Similar rotamers can be
      found in the complexes and the free systems, and the order of the relative
      stability is reversed only in the case of the allenyl derivative. The calculated
      complexation energies are between 80-100 kJ mol(-1) in agreement with flash
      vacuum thermolysis experiments. The photoelectron spectra can be easily described
      in the case of alpha,beta-unsaturated compounds by the change of the direct
      conjugation between the lone electron pair and the pi-bond in the free phosphines
      to hyperconjugation of the sigma(P-B) bond with the unsaturated moiety in the
      corresponding complexed derivatives. In the case of beta,gamma-unsaturated
      derivatives the observed hyperconjugation in phosphines disappears on
      complexation.

PMID- 19381416
TI  - Self-assembly of copper succinate nanoparticles to form anisotropic
      mesostructures.
AB  - Uniform cylindrical rods of copper succinate dihydrate of several microns in
      length and 200 nm in diameter were obtained by the reverse micellar
      (microemulsion) method at room temperature using CTAB as the surfactant. The rod
      like structures are formed by an ordered assembly of spherical particles of 4-5
      nm, which is facilitated by water molecules. The copper succinate particles, in
      the absence of the microemulsion or surfactant, show only spherical geometry,
      while in the presence of the surfactant, thicker rods (compared to as obtained by
      reverse micellar method) of varying length were obtained. The formation of the
      rod-like structure is driven by the permanent dipole moment of the succinate ion,
      which leads to the oriented attachment of the nanoparticles in the presence of
      the surfactant. A new phase (anhydrous copper succinate) is obtained upon heating
      the dihydrate at 75 degrees C, which shows branched and corrugated rods assembled
      from a random arrangement of nanoparticles. The water molecules appear to control
      the morphology of the rods giving smooth rods (ordered arrangement of
      nanoparticles) for the dihydrate while branched or disrupted rods with random
      arrangement of nanoparticles are obtained for the anhydrous phase. The chain
      length of the dicarboxylic acid (ligand) appears to have a role in controlling
      the aspect ratio of these anisotropic mesostructures. The ability to generate
      suitable conditions for self assembly into ordered nanostructures and to control
      the anisotropy would lead us towards a proper design of nanodevices.

PMID- 19381417
TI  - Theoretical and experimental sulfur K-edge X-ray absorption spectroscopic study
      of cysteine, cystine, homocysteine, penicillamine, methionine and methionine
      sulfoxide.
AB  - The experimental sulfur K-edge X-ray absorption near-edge structure (XANES)
      spectra of the amino acids cysteine, homocysteine, penicillamine, methionine,
      including the oxidation products methionine sulfoxide and the disulfide cystine,
      have been analyzed by transition potential DFT calculations. The absolute
      energies and intensities of the main pre-edge sulfur 1s electron transitions have
      been computed to determine the character of the receiving unoccupied molecular
      orbitals (MO), and to investigate the influence of external interactions,
      especially by introducing water molecules hydrogen-bonded to the ionic species
      present in different pH ranges. When the thiol group deprotonates for cysteine,
      homocysteine and penicillamine and also for the cysteine residue in glutathione
      the energy of the main transition, to an MO with antibonding sigma*(S-H)
      character, reduces by approximately 1.1 eV and the receiving MO obtains sigma*(S
      C) character. The changes in transition energy due to hydrogen-bonding were in
      most cases found to be relatively small, although the transition intensities
      could vary significantly due to the changes induced in the molecular charge
      distribution, thereby affecting the shapes of the spectral features. For the
      cysteine and penicillamine zwitterions deconvolution of the experimental spectra
      allowed the microscopic acid dissociation constants to be extracted separately
      for the thiol and the protonated amine groups, pK(a)(S) = 8.5 +/- 0.1 and 8.2 +/-
      0.1, and pK(a)(N) = 8.9 +/- 0.1 and 8.8 +/- 0.1, respectively, with the thiol
      group in both cases being the more acidic. Coordination of cysteine to nickel(II)
      or mercury(II) introduced a new low energy transition involving metal ion
      orbitals in the receiving LUMO. The small experimentally observed energy
      differences between the similar main absorption features of the cysteine and
      methionine zwitterions, 0.2-0.3 eV in comparable surrounding, as well as a minor
      difference in their intensities, are reflected in the calculated transitions. The
      S K-edge XANES spectrum of the disulfide cystine displays a characteristic double
      peak with the lower energy transition (2469.9 eV) into the antibonding sigma*(S
      S) MO. The second peak, at 2471.5 eV in aqueous solution, contains several
      transitions into MOs with sigma*(S-C) character involving also charge transfer to
      the water molecules hydrating the protonated amine groups (NH(3)(+)) of cystine.
      For solid cystine without hydrogen bonding the experimental energy difference
      between the two peaks is 0.2 eV larger, while no such increase occurs for the
      oxidized disulfide of glutathione, with a similar -S-S- bond between its cysteine
      residues as in cystine, because the amine groups are engaged in peptide bonds.
      This study shows that externally induced changes in the intramolecular bonding,
      e.g., by coordination, conformation geometry or hydrogen-bonding, can
      significantly influence the S K-edge spectra, and emphasizes the importance of a
      similar chemical surrounding when choosing the model compounds for standard
      spectra of sulfur functional groups, used to deconvolute composite experimental
      spectra.

PMID- 19381418
TI  - Selective, catalytic aerobic oxidation of alcohols using CuBr(2) and bifunctional
      triazine-based ligands containing both a bipyridine and a TEMPO group.
AB  - Three novel, bifunctional triazine-based ligands, namely , and , containing both
      a TEMPO and a bipyridine moiety have been synthesized. These bpy/TEMPO-based
      molecules have been used as catalyst precursors for the copper-catalyzed aerobic
      oxidation of alcohols to aldehydes and ketones, in the presence of tert-BuOK as
      co-catalyst. The complexes obtained in situ from ligands and with copper(II)
      bromide in a 2:1 acetonitrile/water mixture, selectively catalyze the aerobic
      oxidation of primary benzylic, allylic and aliphatic alcohols and secondary
      benzylic alcohols. The rate of oxidation achieved using compound is slightly
      lower than that of compound . Surprisingly, the [copper/] system is not an
      efficient catalyst. The distinct catalytic behaviour of the three complexes is
      most likely due to the different position of the anchoring point of the
      bipyridine moiety on the triazine core, thereby inducing dissimilar steric
      effects. The effect of the substitution position of the bipyridine unit is
      reflected by the Vis-NIR spectra of the corresponding copper(II) complexes, which
      show similar LMCT and d-d transitions for and , while these absorption bands are
      significantly red-shifted in the case of the [Cu(II)/] complex. These differences
      are indicative of different coordination environments around the Cu(II) centres
      in those compounds.Single-crystal X-ray diffraction studies reveal that [Cu(2)(4
      bpyT)(2)Br(4)](CH(3)CN)(7) () and [Cu(2)(5-bpyT)(2)Br(4)](CH(3)CN)(2) () are
      comparable dinuclear compounds with pentacoordinated copper ions, in a distorted
      square-pyramidal geometry in and in a distorted trigonal-bipyramidal geometry in
      . These two coordination geometries are also reflected by their slightly
      different Vis-NIR results. Cu(6-bpyT)Br(2) () is mononuclear, with the Cu(II) ion
      in a distorted tetrahedral geometry, suggesting a relationship with its catalytic
      inactivity.

PMID- 19381419
TI  - Clear evidence of electron delocalization: synthesis, structure, magnetism, EPR
      and DFT calculation of the asymmetric hexanickel string complex containing a
      single mixed-valence (Ni(2))(3+) unit.
AB  - This paper describes the physical properties of the (Ni(2))(3+) mixed-valence
      unit that is an excellent conductivity-enhanced tool for metal string complexes.

PMID- 19381420
TI  - Synthesis, X-ray crystal structures, magnetism, and DNA cleavage properties of
      copper(II) complexes with 1,4-tpbd ligand.
AB  - Four new copper(II) complexes, [Cu(1,4-tpbd)Br(2)] (), [Cu(2)(1,4
      tpbd)(H(2)O)(4)](ClO(4))(4) (), [Cu(2)(1,4-tpbd)(1,10
      phen)(2)(DMF)(2)](ClO(4))(4) () and [Cu(2)(1,4-tpbd)(2,2'
      bpy)(2)(ClO(4))(2)](ClO(4))(2) (), [1,4-tpbd = N,N,N',N'-tetrakis(2
      pyridylmethyl)benzene-1,4-diamine], have been synthesized to serve as artificial
      nucleases. Single crystal X-ray diffraction reveals that the copper(II) atom has
      a distorted intermediate between square pyramidal and trigonal bipyramidal
      configuration for and a distorted square pyramidal geometry for , while a
      distorted octahedral environment for and . Variable-temperature magnetic
      susceptibility studies (2-300 K) indicate the existence of antiferromagnetic
      coupling between the copper(II) ions in complex . The interactions of the four
      complexes with calf thymus DNA (CT-DNA) have been investigated by UV absorption,
      fluorescent spectroscopy and cyclic voltammetry, and the modes of CT-DNA binding
      for the complexes have been proposed. In the absence of external agents,
      supercoiled plasmid DNA cleavage by the complexes was performed under aerobic
      conditions, the influence on the DNA cleavage process of different complex
      concentrations, reaction times was also studied. The DNA cleavage mechanisms were
      demonstrated with radical scavengers and anaerobic conditions, indicating all
      complexes cleaved pBR322 DNA in 50 mM Tris-HCl/18 mM NaCl buffer (pH = 7.2) at 37
      degrees C through a hydrolytic process. In the four copper(II) complexes, complex
      showed highest cleavage activity with the pseudo-Michaelis-Menten kinetic
      parameters k(cat) = 4.23 h(-1) and K(m) = 2.4 x 10(-5) M.

PMID- 19381421
TI  - Stabilization of the base-off forms of vitamin B(12) and coenzyme B(12) by
      encapsulation of the alpha-axial 5,6-dimethylbenzimidazole ligand with
      cucurbit[7]uril.
AB  - Cucurbit[7]uril (CB[7]) forms very stable complexes with the alpha-axial 5,6
      dimethylbenzimidazole (alpha-DMB) nucleotide base when dissociated from the
      Co(III) center in vitamin B(12) (CNCbl, K(CB[7]) = (7.5 +/- 0.5) x 10(4) dm(3)
      mol(-1)) and coenzyme B(12) (AdoCbl, K(CB[7]) = (3.02 +/- 0.35) x 10(6) dm(3)
      mol(-1)). The inclusion of alpha-DMB ligand facilitates its release from the
      metal center and its subsequent protonation, with significantly higher pK(base
      off) values of 3.77 and 6.61, than determined for the free CNCbl (0.11) and
      AdoCbl (2.67), respectively. Addition of CB[7] to the base-on form of CNCbl at pH
      2 provides for a direct measurement of the rate constant for the dissociation of
      the alpha-DMB ligand from the Co center (k = (4.6 +/- 0.2) x 10(-2) s(-1), DeltaH
      = 93 +/- 2 kJ mol(-1), DeltaS = +41 +/- 6 J K(-1) mol(-1)). The beta-axial 5'
      deoxyadenosyl ligand (beta-Ado) on coenzyme B(12) is bound more weakly by a
      second CB[7] host (K(CB[7]) = (1.1 +/- 0.2) x 10(3) dm(3) mol(-1)), however
      inclusion of the beta-Ado ligand has no effect on the kinetics of its heterolytic
      photodissociation from the Co(III) center.

PMID- 19381422
TI  - Uranyl monocarboxylates of aromatic acids: a density functional model study of
      uranyl humate complexation.
AB  - Using a scalar relativistic all-electron density functional method, we studied
      uranium(VI) complexation with benzoic acid and its derivatives in aqueous
      solution as models of uranyl humates. We explored monodentate, bidentate, and
      chelate coordination of various isomers of methyl and hydroxyl substituted
      benzoic acid ligands. Monodentate complexes were determined to be energetically
      preferred as long as entropy effects were neglected. However, bidentate
      structures were favored at the Gibbs free energy level. Coordination of aromatic
      carboxylic acids tends to be weaker than that of aliphatic ones, while structural
      characteristics were determined to be quite similar. Optimized geometries yield
      uranyl bonds and U-C distances in agreement with EXAFS results for
      monocarboxylate of benzoate and p-hydroxy benzoate. Average uranyl-oxygen
      distances to equatorial ligands, U-O(eq), are shorter than in experiment, which
      is tentatively rationalized by variations in the coordination numbers. As for
      aliphatic monocarboxylate complexes studied earlier, U-O(eq) values of benzoic
      acid derivatives do not discriminate mono- and bidentate coordinated species.
      Structures and energies determined support the interpretation of uranyl humate
      complexes as bidentate carboxylate species with fivefold coordination of uranyl.

PMID- 19381423
TI  - Rhodium(I) and iridium(I) complexes containing bidentate phosphine-imidazolyl
      donor ligands as catalysts for the hydroamination and hydrothiolation of alkynes.
AB  - A series of novel cationic and neutral rhodium and iridium complexes containing
      bidentate phosphine-imidazolyl donor ligands of the general formulae
      [M(ImP)(COD)]BPh(4) (M = Rh, ImP = ImP2, 3; ImP1a, 4a; ImP1b, 4b and M = Ir, ImP
      = ImP2, 5; ImP1a, 6a and ImP1b, 6b), [Ir(ImP)(CO)(2)]BPh(4) (ImP = ImP2, 7;
      ImP1a, 8a and ImP1b, 8b), [Rh(ImP1b)(CO)(2)]BPh(4) (10b) and [M(ImP)(CO)Cl] (M =
      Rh, ImP = ImP2, 11; ImP1b,12 and M = Ir, ImP = ImP2, 13; ImP1b, 14 ) where COD =
      1,5-cyclooctadiene, ImP2 = 1-methyl-2-[(2-(diphenylphosphino)ethyl]imidazole, 1;
      ImP1a = 1-methyl-2-[(diphenylphosphino)methyl]imidazole, 2a and ImP1b = 2
      [(diisopropylphosphino)methyl]-1-methylimidazole, 2b were successfully
      synthesised. The solid state structures of 3, 6a, 11 and 12 were determined by
      single crystal X-ray diffraction analysis. A number of these complexes are
      effective as catalysts for the intramolecular hydroamination of 4-pentyn-1-amine
      to 2-methyl-1-pyrroline. The cationic complexes are significantly more effective
      than analogous neutral complexes. The cationic iridium complex 8b , containing
      the phosphine-imidazolyl ligand with the bulky isopropyl groups on the phosphorus
      donor, is more efficient than analogous complexes with the phenyl substituents on
      the phosphorus donor atom, 7 and 8a. The complexes 7-8b are also moderately
      effective in catalysing the addition of thiophenol to a range of terminal
      alkynes. In contrast to the hydroamination reaction, placement of the isopropyl
      group on the phosphorus donor leads to a decrease in the reactivity of the
      resulting metal complexes as catalysts for the hydrothiolation reaction.

PMID- 19381424
TI  - Psychiatric disorders in students in six French universities: 12-month
      prevalence, comorbidity, impairment and help-seeking.
AB  - PURPOSE: Few studies have explored the prevalence of psychiatric disorders (PD)
      among university students. This article aims to study 12-month prevalence of PD
      in university students, their socio-economic correlates, impairment in daily life
      and help-seeking behaviours. METHODS: Cross-sectional study of randomly selected
      first-year students aged 18-24 years, enrolled in one of the six universities in
      south-eastern France in 2005-2006. We used the WHO CIDI-Short Form to derive DSM
      IV diagnoses and the Sheehan disability scale to evaluate impairment. We studied
      their correlates with multiple logistic regressions. RESULTS: The 12-month
      prevalence of major depressive disorder (MDD), anxiety disorders (AD) and
      substance use disorders (SUD) were 8.9% (95% CI: 7.2-10.9), 15.7% (95% CI: 13.5
      18.2) and 8.1% (95% CI: 6.7-9.8), respectively. MDD was associated with
      precarious economic situation (OR = 1.83; 95% CI: 1.03-3.23), AD with a
      precarious job or unemployment of the father (OR = 2.08; 95% CI: 1.04-4.14) and
      SUD with higher educational level of father (OR = 2.17; 95% CI: 1.28-3.67) or
      having a paid job (OR = 1.82; 95% CI: 1.06-3.13). "Marked" or "extreme"
      impairment (score > or =7 for at least one of the domains in the Sheehan scale)
      was noted for 51.7% of students presenting a PD and was even more frequent in the
      presence of MDD/AD comorbidity. Only 30.5% of the students with a PD had sought
      professional help in the past 12 months. CONCLUSIONS: This study provides new
      results regarding university students suggesting a link between precarious
      economic situations and MDD. The frequent impairment arising from PD alongside
      low rates of help-seeking suggests that PD could be one of the factors in
      academic failure in first year of university. These results should be used to
      improve prevention and care of PD in university students in France.

PMID- 19381425
TI  - Assessment of explanatory models of mental illness: effects of patient and
      interviewer characteristics.
AB  - BACKGROUND: Explanatory models (EMs) refer to patients' causal attributions of
      illness and have been shown to affect treatment preference and outcome. Reliable
      and valid assessment of EMs may be hindered by interviewer and respondent
      disparities on certain demographic characteristics, such as ethnicity. The
      present study examined (a) whether ethnic minority patients reported different
      EMs to ethnically similar interviewers in comparison with those with a different
      ethnicity, and (b) whether this effect was related to respondents' social
      desirability, the perceived rapport with the interviewer and level of uncertainty
      toward their EMs. METHODS: A total of 55 patients of Turkish and Moroccan origins
      with mood and anxiety disorders were randomly assigned to ethnically similar or
      dissimilar interviewers. EMs were assessed, using a semi-structured interview,
      across 11 different categories of causes. RESULTS: Participants who were
      interviewed by an ethnically similar interviewer perceived interpersonal,
      victimization and religious/mystical causes as more important, whereas interviews
      by ethnically dissimilar interviewers generated higher scores on medical causes.
      These effects were not mediated by the perceived rapport with the interviewer,
      and social desirability had a modest impact on the results. Higher uncertainty
      among participants toward medical and religious/mystical causes seemed to be
      associated with greater adjustment in the report of these EMs. CONCLUSION: The
      findings have significant implications for interviewer selection in
      epidemiological research and clinical practice.

PMID- 19381426
TI  - Prevalence of psychiatric disorders in a Brazilian birth cohort of 11-year-olds.
AB  - OBJECTIVE: To estimate the prevalence of psychiatric disorders in preadolescents
      aged 11-12 years from a birth cohort in a southern Brazilian city. METHODS: This
      is a cross-sectional investigation nested in a cohort study with a two-phase
      design: screening and diagnosis. In the screening phase, 4,452 preadolescents and
      their mothers were interviewed with the Strengths and Difficulties Questionnaire
      (SDQ). In the diagnostic phase, all preadolescents with a positive SDQ (n = 122)
      and their mothers answered the Development and Well-Being Assessment for Children
      and Adolescents (DAWBA). A sample randomly selected among the cohort participants
      with a negative SDQ served as a control group (158 subjects and their mothers)
      and was also assessed using the DAWBA. RESULTS: After adjustment for the
      performance of the screening instrument, 10.8% (95% CI 7.1-14.5) of the
      preadolescents showed at least one psychiatric disorder according to either the
      DSM-IV or the ICD-10. The most prevalent disorders were disruptive behavior
      (prevalence rates were 8.5% according to the DSM-IV and 7.1% according to the ICD
      10) and anxiety disorders (prevalence rates were 6.0% according to the DSM-IV and
      6.2% according to the ICD-10). CONCLUSION: Both overall and individual prevalence
      rates of psychiatric disorders found in this study are in the same range of other
      international studies, although slightly higher than findings from developed
      countries. The results corroborate previous findings from other epidemiological
      studies in children and adolescents suggesting the universality of psychiatric
      disorders across cultures.

PMID- 19381428
TI  - Effects of soil amendments on the extractability and speciation of cadmium, lead,
      and copper in a contaminated soil.
AB  - The effects of chemical amendments including zeolite, compost and mesoporous
      molecular sieves (MCM-41) on the extractability and speciation of heavy metals
      (Cd, Pb and Cu) in a contaminated soil were investigated. Results showed that the
      application of soil amendments decreased Cd, Pb and Cu uptake by the shoots of
      pakchoi, up to 44.2-53.2%, 30.2-42.7% and 16.9-22.1%, respectively, compared with
      the control. Among the three amendments, zeolite and MCM-41 were more efficient
      in reducing Cd and Cu uptake, while compost was more efficient in reducing Pb
      uptake by the plants. The growth of pakchoi was improved in amended soils due to
      the action of chemical amendments.

PMID- 19381427
TI  - Are attitudes towards mental health help-seeking associated with service use?
      Results from the European Study of Epidemiology of Mental Disorders.
AB  - OBJECTIVE: To investigate the prevailing attitudes towards mental health help
      seeking in Europe, their correlates, and whether these attitudes are associated
      with actual service use for mental health problems. METHOD: Data were derived
      from the European Study of Epidemiology of Mental Disorders, a survey
      representative of the adult population of six countries: Belgium, France,
      Germany, Italy, the Netherlands and Spain (n = 8,796). The World Mental Health
      Composite International Diagnostic Interview was used to assess attitudes and DSM
      IV diagnoses. The attitudes referred to beliefs that the respondents would seek
      professional help when faced with a serious emotional problem, would feel
      comfortable talking about personal problems with a professional, would not be
      embarrassed if friends knew about the professional help, and respondents'
      perceived effectiveness of mental health care. RESULTS: Almost a third of the
      respondents held the view that professional care was worse than or equal to no
      help when faced with serious emotional problems. Female gender, being younger
      than 65 years of age, high income, living in Spain or Italy, presence of mood
      disorder and previous service use were associated with at least two of the four
      assessed attitudes towards mental health help-seeking. All four attitudes were
      significantly associated with mental health care use, also after adjustment for
      previous service use. CONCLUSION: The low perceived effectiveness of professional
      care calls for serious action aiming to improve the visibility and credibility of
      the mental health care sector.

PMID- 19381429
TI  - May an altered hypothalamo-pituitary-adrenal axis contribute to cortical bone
      damage in primary hyperparathyroidism?
AB  - Cortisol secretion has been reported to be increased in primary
      hyperparathyroidism (PHPT). Our aim was to evaluate circulating and urinary
      cortisol levels and the relationships with biochemical and bone parameters in
      patients with PHPT at the time of diagnosis. We studied 180 consecutive patients
      with PHPT (mean age +/- SD 60.0 +/- 13.2 years; F/M 140/40, BMI 25.8 +/- 4.8
      kg/m(2)) and 56 subjects with incidentally discovered adrenal adenoma who served
      as controls (age 56.2 +/- 12.8 years, F/M 40/16, BMI 25.7 +/- 3.9 kg/m(2)). Serum
      morning and midnight cortisol and urinary free cortisol were measured in both
      groups. In PHPT patients bone mineral density was measured at the lumbar spine,
      femur, and forearm. Serum morning cortisol and urinary cortisol were similar in
      PHPT patients and controls, whereas midnight cortisol was higher in PHPT patients
      (5.3 +/- 4.7 vs. 2.9 +/- 0.9 microg/dL, P = 0.001). In this group, midnight
      cortisol correlated positively with age (r = 0.27, P = 0.008) and negatively with
      forearm (r = -0.36, P = 0.003) and total-femur T score (r = -0.30, P = 0.02).
      Multivariate regression analysis, including age, calcium, parathyroid hormone
      (PTH), and midnight cortisol as independent variables and forearm T score as
      dependent variable, indicated that age (beta = -0.29, P < 0.0001), PTH (beta = 
      0.33, P < 0.0001), and midnight cortisol (beta = -0.14, P < 0.04) were
      independently associated with forearm T score. Our findings show increased
      midnight cortisol levels in patients with PHPT, indicating a subtle alteration of
      the hypothalamo-pituitary-adrenal axis dynamics that is unrelated to the degree
      of disease activity; further data are needed to demonstrate the supplementary
      effect of this subtle alteration to bone damage in this condition.

PMID- 19381430
TI  - Survival after transarterial embolization for spontaneous ruptured hepatocellular
      carcinoma.
AB  - OBJECTIVES: To examine the survival of patients with spontaneous ruptured
      hepatocellular carcinoma treated with transarterial embolization (TAE). METHODS
      AND MATERIALS: Patients diagnosed with spontaneous ruptured hepatocellular
      carcinoma treated with TAE were retrospectively studied. Hospital records were
      reviewed and data were collected and analyzed from the years 2000-2006. A total
      of 62 patients who had been diagnosed with spontaneous ruptured hepatocellular
      carcinoma were managed in our hospital during this period. RESULTS: All 62
      patients (who had been diagnosed with ruptured hepatocellular carcinoma and were
      managed in our hospital) patients were treated with TAE, with a success rate of
      91% (57/62). Early mortality (within 30 days after rupture) was 38%. Factors that
      were associated with early mortality were old age, low hemoglobin at
      presentation, elevated bilirubin at presentation, prolonged prothrombin time at
      presentation (INR > 1.3), low albumin level at presentation, and unsuccessful
      embolization. A low albumin level was the only independent risk factor for early
      mortality. The overall median survival time was 39 days. Surgical resections were
      possible in seven patients. Their cumulative survival was significantly longer (P
      = 0.002) than that of patients managed with non-operative treatment after
      embolization. CONCLUSION: Transarterial embolization (TAE) can achieve good
      hemostasis, though low albumin level, which reflects poor liver reserve, may
      predict early mortality. Portal vein thrombosis should not be regarded as an
      absolute contraindication for TAE. Staged surgical resection after embolization
      is safe and produces a good survival outcome.

PMID- 19381431
TI  - The introduction of a simple maneuver to reduce the risk of postoperative
      bleeding after major hepatectomies.
AB  - BACKGROUND/PURPOSE: In major hepatectomies, postoperative increases in central
      venous pressure (CVP) may cause suture failure and massive bleeding. The aim of
      our study is to test the application of an intraoperative maneuver to reduce the
      risk of postoperative bleeding. METHODS: Our study included 172 consecutive
      patients who had major liver resection with selective hepatic vascular exclusion
      and sharp transection of the liver parenchyma. An intraoperative maneuver (5 s
      occlusion of the hepatic vein) was applied in an alternating way, and the
      patients were assigned to two groups: Cohort A (n = 86), that was granted the
      maneuver, and Cohort B (n = 86), that was used as a control group. RESULTS: In
      Cohort A, application of the maneuver was successful in demonstrating bleeders
      under low CVP levels. Cohort A had lower rate of massive bleeding requiring
      emergency reoperation (2.3 vs 5.8%, P = 0.049), less postoperative blood
      transfusions (13 vs 24%, P = 0.042), lower morbidity (20 vs 35%, P < 0.045) and
      shorter hospital stay compared to Cohort B. CONCLUSIONS: Hepatectomies conducted
      under low CVP are prone to postoperative hemorrhage which can be prevented if the
      final bleeding control is performed under high pressure in the hepatic veins.
      Application of our testing maneuver effectively unmasked previously undetectable
      bleeding veins.

PMID- 19381432
TI  - Association of homozygous SDF-1 3'A genotype with proliferative diabetic
      retinopathy.
AB  - Stromal cell-derived factor 1 (SDF-1) is involved in the development of
      experimental proliferative retinopathy. Since little data are available on the
      genetic predisposition or on biomarkers predicting the development of
      proliferative retinopathy, we assessed the distribution of the SDF-1 3'A genotype
      in 130 diabetic patients with retinopathy. In patients with proliferative
      retinopathy, the frequency of the homozygous SDF-1 3'A genotype was significantly
      higher than in patients with non-proliferative retinopathy (10.9% of PDR vs. 0 of
      NPDR, P = 0.01). This association was confirmed when type 2 diabetes patients
      were analysed separately (10.3% of PDR vs. 0 of NPDR, P = 0.03). The finding that
      homozygous carriers of the SDF-1 3'A genotype are more frequent in diabetes
      patients with proliferative retinopathy suggests a possible role of this genotype
      in the development of sight-threatening diabetic retinopathy.

PMID- 19381433
TI  - Possible overlap between reversible cerebral vasoconstriction syndrome and
      symptomatic vasospasm after aneurysmal subarachnoid hemorrhage.
AB  - A 34-year-old woman with a previous history of severe headache ("thunderclap")
      was admitted with a diagnosis of aneurysmal subarachnoid hemorrhage (SAH). The
      patient developed symptomatic vasospasm on day 5 that resolved rapidly after
      having increased arterial blood pressure. She experienced also short-lasting
      excruciating headache. On day 12, while velocities had normalised, as revealed by
      transcranial Doppler (TCD), for more than 48 h, she developed aphasia and right
      hemiplegia associated with diffuse segmental vasospasm on the left middle
      cerebral artery. Intra-arterial infusion of vasodilatory agents was required.
      Recurrence of symptomatic vasospasm was noted on day 25, with a great number of
      territories involved as shown in the cerebral angiogram. A second intra-arterial
      treatment was needed. The patient complained of multiple episodes of extremely
      severe headache ("thunderclap"), with also transient dysarthria and hemiparesia
      on day 30. She was discharged on day 38 after full recovery. The clinical and
      TCD/radiological findings were consistent with a reversible cerebral
      vasoconstriction syndrome overlapping SAH related symptomatic vasospasm.

PMID- 19381434
TI  - Staged bilateral deep brain stimulation of the subthalamic nucleus for the
      treatment of Parkinson's disease.
AB  - BACKGROUND: Several investigators have described the efficacy and safety of
      unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the
      treatment of Parkinson's disease (PD). Some patients who underwent unilateral STN
      DBS required additional surgery on the contralateral side because the unilateral
      treatment was insufficient. The goal of this study was to assess the efficacy and
      safety of staged bilateral STN DBS compared to the simultaneous bilateral
      procedure. METHODS: Ten patients with medically intractable PD underwent staged
      bilateral STN DBS, and 12 patients underwent a simultaneous bilateral procedure.
      Clinical assessments were performed preoperatively and 6 months after the last
      surgery using the Unified Parkinson's Disease Rating Scale (UPDRS), motor and
      activity of daily living (ADL) subscores, and Hoehn and Yahr stages. FINDINGS:
      Both the staged and simultaneous groups experienced significant improvement in
      the UPDRS motor and ADL scores, and the Hoehn and Yahr stages. There were no
      statistical differences between the two groups in the percent improvement in
      UPDRS scores. The rate of adverse events in the staged group (20%) was less than
      that of the simultaneous group (42%), although the difference was not
      statistically significant. CONCLUSIONS: Both the staged bilateral STN DBS and the
      simultaneous bilateral procedure are effective and safe treatment options, but
      the staged bilateral procedure may be regarded as the preferred choice for the
      treatment of some patients.

PMID- 19381435
TI  - Regulation of megakaryocytic differentiation of K562 cells by FosB, a member of
      the Fos family of AP-1 transcription factors.
AB  - The regulation of megakaryocytic differentiation is poorly understood. Using K562
      cells, which can partly recapitulate the process in response to phorbol 12
      myristate 13-acetate (PMA), we performed microarray-based gene expression
      profiling to identify genes that play significant roles in megakaryopoiesis.
      Here, we describe the function of FosB, an AP-1 transcription factor. FosB is
      induced in PMA treated K562 cells in a sustained manner and forms an active AP-1
      protein-DNA complex. Down-regulation of FosB with specific shRNAs inhibited the
      induction of CD41, a specific cell surface marker of megakaryocytes. We also show
      that activation of the PKC-MEK-ERK signaling pathway is required for induction of
      FosB and CD41. Finally, we cross-examined the microarray data in conjunction with
      gene function annotation data to identify additional target genes of FosB. We
      define 3 genes, INHBA, CD9, and ITGA2B as regulatory targets of FosB and show
      that CD9, in particular, is a direct target of FosB.

PMID- 19381437
TI  - The mammalian NudC-like genes: a family with functions other than regulating
      nuclear distribution.
AB  - Nuclear distribution gene C homolog (NudC) is a highly conserved gene. It has
      been identified in different species from fungi to mammals. The high degree of
      conservation, in special in the nudC domain, suggests that they are genes with
      essential functions. Most of the identified genes in the family have been
      implicated in cell division through the regulation of cytoplasmic dynein. As for
      mammalian genes, human NUDC has been implicated in the migration and
      proliferation of tumor cells and has therefore been considered a possible
      therapeutic target. There is evidence suggesting that mammalian NudC is also
      implicated in the regulation of the inflammatory response and in thrombopoiesis.
      The presence of these other functions not related to the interaction with
      molecular motors agrees with that these genes and their products are larger in
      size than their microbial orthologous, indicating that they have evolved to
      convey additional features.

PMID- 19381438
TI  - Paraplegia of spinal epidural compression by metastatic breast cancer and urgent
      radiotherapy-timeliness for naught?
AB  - Four patients who became paraplegic because of spinal epidural compression by
      metastatic breast cancer were treated for palliation by external beam radiation.
      None of the four regained ambulation after therapy. Our findings place in
      question the urgent need for radiotherapy in these paralytic people with the
      disorder, especially when they are pain-free.

PMID- 19381439
TI  - Whole-brain radiotherapy and tumor bed radiosurgery following resection of
      solitary brain metastases.
AB  - A standard approach to solitary brain metastases is resection followed by whole
      brain radiation therapy (WBRT). Despite WBRT, the tumor bed remains a common site
      of failure. We reviewed outcomes following adjuvant WBRT with tumor bed
      radiosurgery (SRS). We retrospectively identified patients having undergone
      neurosurgical resection of a single brain metastasis followed by adjuvant WBRT
      and tumor bed SRS. SRS dose selection was independent of target volume (10 Gy
      peripheral dose). Outcomes were calculated actuarially. Patients were censured
      for local control at the time of last imaging. From 2005 to 2008, 27 patients
      were treated with WBRT and tumor bed SRS. Median age was 58.7 years, median KPS
      80%. The primary malignancy was non-small cell lung cancer in 70%. Median follow
      up was 9.7 months. Following the combination of surgery, WBRT and SRS the median
      overall survival was 17.6 months. Actuarial 2-year local control was 94%. The SRS
      boost was well tolerated with one patient (4%) requiring reoperation for
      symptomatic radiation necrosis 16 months post treatment. Radiosurgery can be
      safely added to WBRT as an adjuvant treatment following resection of a single
      brain metastasis. In our retrospective series, this combination treatment
      produced a high rate of local control.

PMID- 19381436
TI  - The annexins: spatial and temporal coordination of signaling events during
      cellular stress.
AB  - Annexins are a family of structurally related, Ca2+-sensitive proteins that bind
      to negatively charged phospholipids and establish specific interactions with
      other lipids and lipid microdomains. They are present in all eukaryotic cells and
      share a common folding motif, the "annexin core", which incorporates Ca2+- and
      membrane-binding sites. Annexins participate in a variety of intracellular
      processes, ranging from the regulation of membrane dynamics to cell migration,
      proliferation, and apoptosis. Here we focus on the role of annexins in cellular
      signaling during stress. A chronic stress response triggers the activation of
      different intracellular pathways, resulting in profound changes in Ca2+ and pH
      homeostasis and the production of lipid second messengers. We review the latest
      data on how these changes are sensed by the annexins, which have the ability to
      simultaneously interact with specific lipid and protein moieties at the plasma
      membrane, contributing to stress adaptation via regulation of various signaling
      pathways.

PMID- 19381440
TI  - CNS recurrence of primary mediastinal large b-cell lymphoma after complete
      remission.

PMID- 19381441
TI  - Glioma recurrence versus radiation necrosis: accuracy of current imaging
      modalities.
AB  - Treatment for brain gliomas is a combined approach of surgery, radiation therapy
      and chemotherapy. Nevertheless, high-grade gliomas usually recur despite
      treatment. Ionizing radiation therapy to the central nervous system may cause
      post-radiation damage. Differentiation between post-irradiation necrosis and
      recurrent glioma on the basis of clinical signs and symptomatology has not been
      possible. Computed tomography (CT) and magnetic resonance imaging (MRI) suffer
      from significant limitations when applied to differentiate recurrent brain tumor
      from radiation necrosis. We reviewed the contribution of recent MRI techniques,
      single-photon emission CT and positron emission tomography to discriminate
      necrosis for glioma recurrence. We concluded that despite the progress being
      made, further research is needed to establish reliable imaging modalities that
      distinguish between true tumour progression and treatment-related necrosis.

PMID- 19381442
TI  - Early metabolic responses in temozolomide treated low-grade glioma patients.
AB  - Amino acid transport and protein synthesis are important steps of tumor growth.
      We investigated the time course of tumor metabolism in low-grade gliomas (LGG)
      during temozolomide chemotherapy, and compared metabolic responses as measured
      with positron emission tomography (PET) with volume responses as revealed by
      magnetic resonance imaging (MR). A homogeneous population of 11 patients with
      progressive non-enhancing LGG was prospectively studied. Imaging was done at 6
      months intervals starting six months, and in a second series starting three
      months after treatment initiation. F-18 fluoro-ethyl-L-tyrosine (FET) uptake was
      quantified with PET as metabolically active tumor volume, and was compared with
      the tumor volume on MR. Response was defined as >or=10% reduction of the initial
      tumor volume. Eight patients showed metabolic responses. Already 3 months after
      start of chemotherapy the active FET volumes decreased in 2 patients to a mean of
      44% from baseline. First MR volume responses were noted at 6 months. Responders
      showed a volume reduction to 31 +/- 23% (mean +/- SD) from baseline for FET, and
      to 73 +/- 26% for MR. The time to maximal volume reduction was 8.0 +/- 4.4 months
      for FET, and 15.0 +/- 3.0 months for MR. The initial metabolic response
      correlated with the best volume response on MR (Spearman Rank P = 0.011).
      Deactivation of amino acid transport represents an early indicator of
      chemotherapy response in LGG. Response assessment based on MR only has to be
      reconsidered. The time window obtained from PET may assist for individual
      treatment decisions in LGG patients.

PMID- 19381443
TI  - Assessment of cetuximab efficacy by bioluminescence monitoring of intracranial
      glioblastoma xenograft in mouse.
AB  - A glioblastoma multiforme xenograft was established in athymic nude mice via
      inoculation of glioblastoma cells that stably express luciferase (U87MG-LucNeo),
      and was monitored weekly using bioluminescence imaging (BLI). In the control
      groups, a steep rise in the signal was associated with the death of mice. As an
      adjuvant therapy, cetuximab (0.5 mg, two times) was intraperitoneally
      administered 4 weeks after nitrosourea treatment. For a salvage therapy,
      cetuximab (0.5 mg, two times) was intraperitoneally administered when recovery of
      the bioluminescence signal was detected after nitrosourea monotherapy. The
      antitumor effects of cetuximab adjuvant therapy were superior to those of
      nitrosourea monotherapy and cetuximab salvage therapy. This finding was
      consistent with the results from a survival comparison among nitrosourea
      monotherapy, adjuvant and salvage therapy with cetuximab. These results suggest
      that BLI could be used as a simple tool for predicting the efficacy of various
      anticancer treatments in mouse models of brain tumors. The administration of
      cetuximab as an adjuvant to the conventional chemotherapeutic agent is more
      efficient than salvage therapy.

PMID- 19381444
TI  - Intrathecal liposomal cytarabine in children under 4 years with malignant brain
      tumors.
AB  - Infants and very young children with malignant brain tumors usually have
      unfavourable locations and are not candidates for craniospinal irradiation. New
      therapeutic approaches must be attempted to improve poor survival rates. The
      primary goal of the present study was to report on the safety profile and
      toxicity of intrathecal administration of liposomal cytarabine in children <4
      years with malignant brain tumors. This is the first study including this group
      of patients receiving intrathecal liposomal cytarabine. Nine patients with a
      median age of 26 months were eligible for the study. The diagnoses were
      ependymoma (3), peripheral neuroectodermic tumor (PNET) (2), meduloblastoma,
      atypical teratoid rhabdoid tumor (ATRT), cerebral lymphoma, and rhabdomyosarcoma
      with CNS invasion. Liposomal cytarabine at doses between 20 and 35 mg were
      administered by lumbar puncture. Dexamethasone was given for arachnoiditis
      prophylaxis. A total of 44 doses (median = 6) of liposomal cytarabine were
      administered. Neurological side effects possibly related to liposomal cytarabine
      were observed in five patients (55.6%). This incidence was higher than previously
      reported in children older than 3 years. Eight of the patients (89%) experienced
      an initial improvement of clinical symptoms after initiation treatment, confirmed
      by MRI. This study demonstrates the feasibility of using intrathecal liposomal
      cytarabine in children under 4 years of age with malignant brain tumors.

PMID- 19381445
TI  - Glioma-associated endothelial cells are chemoresistant to temozolomide.
AB  - Temozolomide is considered the standard of care and drug of choice for the
      treatment of initially diagnosed malignant gliomas. Although well tolerated,
      temozolomide still has limited clinical efficacy. Following drug treatment,
      patient prognosis still remains poor; tumor recurrence is almost universal. We
      hypothesized that this lack of effectiveness with temozolomide is because this
      drug does not target the glioma microenvironment, which is highly vascular in
      malignant gliomas. To test this hypothesis we analyzed the effects of
      temozolomide on the tumor vasculature in vitro and in vivo. We found that this
      drug did not affect the viability or proliferation rate of endothelial cells
      isolated from human glioma specimens, although temozolomide was highly cytotoxic
      to the glioma cell lines U87MG and U251. Furthermore, temozolomide did not
      inhibit the migration of these glioma-associated endothelial cells, a key
      mechanism responsible for tumor angiogenesis. In in vivo studies, using the
      intracranial glioma mouse model, temozolomide did not cause a pronounced effect
      on microvessel density. Our findings show that temozolomide has no apparent
      effect on the glioma vascular microenvironment. Thus combination therapy with
      anti-vascular agents may enhance temozolomide effectiveness as glioma therapeutic
      protocol.

PMID- 19381446
TI  - Systemic sagopilone (ZK-EPO) treatment of patients with recurrent malignant
      gliomas.
AB  - It has been demonstrated that sagopilone (ZK-EPO) has antitumor activity in human
      orthotopic glioma models in vitro and in vivo. The objective of this study was to
      evaluate the safety and efficacy of ZK-EPO in patients with pretreated, recurrent
      malignant gliomas. Fifteen patients with recurrent malignant gliomas who had
      received prior surgery, radiotherapy, and >or=2 lines of alkylating chemotherapy
      were recruited. ZK-EPO (16 mg/m(2)) was administered iv for 3 h every 21 days.
      The primary end point was six months progression-free survival (PFS-6); secondary
      end points were safety, toxicity, response rate, and median time to progression
      (TTP). Magnetic resonance imaging (MRI) evaluations were performed every two
      cycles and toxicity was evaluated at each cycle using common terminology criteria
      for adverse events (CTCAE 3.0). A median of four cycles was administered. The
      median TTP was 13 weeks. PFS-6 was achieved in five patients (33%), three with
      glioblastoma multiforme and two with anaplastic astrocytoma. The most common
      treatment-related adverse event was neuropathy, which occurred in 6/15 patients.
      ZK-EPO had an acceptable safety profile and clinically relevant activity in
      patients with pretreated, recurrent malignant gliomas.

PMID- 19381447
TI  - An approach to the management of patients with residual Cushing's disease.
AB  - The evaluation and management of patients with residual Cushing's disease is one
      of the more complex issues facing neurosurgeons and neuroendocrinologists in
      clinical practice. There is considerable controversy over several relevant issues
      such as the timing of the assessment of whether a patient is in remission, what
      biochemical parameters define remission, the most appropriate course of action to
      take after residual disease has been defined, etc. As a consequence of the
      controversies, treating physicians develop notions and fall into certain practice
      patterns based on evidence of varying levels, their anecdotal experiences, and
      information gleaned from scientific meetings. This practice pattern, we believe,
      constitutes the "art of medicine." We conducted a PubMed literature search to
      identify manuscripts containing data relevant to Cushing's disease, outcomes of
      various therapeutic modalities, and recurrences. Reference lists were used to
      identify additional relevant manuscripts. We focused our review on manuscripts
      that included reasonably large series of patients, those reflecting the
      experience of pituitary centers and physicians recognized as experts in the
      field, and those papers felt to represent seminal contributions to the
      literature. Furthermore, trends in the evaluation and management of relevant
      patients have been incorporated by the senior author who has seen and evaluated
      over 750 patients with documented Cushing's syndrome over the past 18 years in
      clinical practice. An analysis of current evidence indicated that, despite
      advances in neurosurgical techniques and recent developments in adjuvant
      therapies, patients with residual Cushing's disease present significant
      management challenges to treating physicians. In this era, however, it is indeed
      possible to gain control of the hypercortisolism in most patients. Despite the
      wide variability in research methodology designed to collect relevant data, a
      step-wise approach to the management of these patients can be achieved. A logical
      step-wise approach to the evaluation of postoperative patients with Cushing's
      disease is essential. Patients with residual disease require the development of
      an individualized plan of management that takes into account numerous factors
      pertaining to status of disease, the experience of treating physicians, and
      available therapeutic modalities.

PMID- 19381448
TI  - Allostatic tumor-burden induces depression-associated changes in hepatoma-bearing
      mice.
AB  - The high incidence of depression among cancer patients has created the need for
      deeper insights into its underlying pathophysiological mechanism. The aim of the
      current study is to demonstrate the presence of depressive states due to
      allostatic tumor-burden in the animal model, and if possible to elucidate the
      mechanism(s) by which the tumor might induce the depressive state. Stress-related
      behavioral responses and tumor weight were evaluated 6, 8, and 12 days after
      implantation of H22 hepatoma cells into the right flank of mice. Brain changes
      associated with depression were also observed 12 days after tumor implantation.
      The mice that were subjected to tumor-burden exhibited a significant depression
      like state which manifested as behavioral changes including prolonged time spent
      immobile in the tail suspension test and reduced spontaneous motor activity with
      tumor progression. These behavior indices changed significantly 12 days after
      tumor implantation and were improved by the antidepressant fluoxetine.
      Correspondingly, the activity of superoxide dismutase (SOD) in the cerebrum and
      the expression of glia maturation factor beta (GMF-beta) and brain-derived
      neurotrophic factor (BDNF) in the hippocampus were significantly decreased in
      tumor-bearing mice, and these decreases were also reversed by fluoxetine. Taken
      together, these data indicate that tumor-burden might induce depressive-related
      behavior and brain changes, and suggest that antidepressants might not only
      palliate depression symptoms but also modify disease processes in the auxiliary
      treatment of cancer.

PMID- 19381450
TI  - Response variability to aspirin and one-year prediction of vascular events in
      patients with stable coronary artery disease.
AB  - The aim of this study was to assess the association between "aspirin non
      responsiveness" in patients with coronary artery diseases (CAD) and the risk of
      major adverse cardiovascular events (MACE). 204 patients with CAD receiving
      aspirin (250 mg/d) were included. Both Collagen/Epinephrine Closure Time (CEPI
      CT) and urinary Thromboxane B2 (uTxB2) concentration was used to determine the
      patients aspirin responsiveness. The clinical primary endpoint was the occurrence
      of MACE including: cardiovascular death, MI, stroke or transient ischemic attack.
      The secondary endpoint was the occurrence of Recurrent Acute Vascular Event
      (RAVE: MI, stroke or transient ischemic attack). After 1-year follow-up, no
      responders diagnosed by CEPI-CT had a trend for higher risk of MACE (13% vs 7.4%;
      P = 0.22) and significant higher risk of RAVE (OR = 2.1; 95%CI: 1.7-2.4; P =
      0.01) when compared to good responders. Multivariate analysis showed that CEPI-CT
      < 143 s was the only independent predictor of RAVE (OR = 6.3; 95% CI: 1.2-32.2; P
      = 0.026). Aspirin non-responsiveness, diagnosed by the uTxB2, was not associated
      with an increased risk of either MACE or RAVE. Our results, reinforce the
      importance of being able to diagnose laboratory "aspirin non responsiveness", and
      extend the evidence that aspirin non responsiveness may explain in part the
      occurrence of RAVE.

PMID- 19381449
TI  - Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98,
      BT4C, RT-2 and CNS-1 gliomas.
AB  - In this review we will describe eight commonly used rat brain tumor models and
      their application for the development of novel therapeutic and diagnostic
      modalities. The C6, 9L and T9 gliomas were induced by repeated injections of
      methylnitrosourea (MNU) to adult rats. The C6 glioma has been used extensively
      for a variety of studies, but since it arose in an outbred Wistar rat, it is not
      syngeneic to any inbred strain, and its potential to evoke an alloimmune response
      is a serious limitation. The 9L gliosarcoma has been used widely and has provided
      important information relating to brain tumor biology and therapy. The T9 glioma,
      although not generally recognized, was and probably still is the same as the 9L.
      Both of these tumors arose in Fischer rats and can be immunogenic in syngeneic
      hosts, a fact that must be taken into consideration when used in therapy studies,
      especially if survival is the endpoint. The RG2 and F98 gliomas were both
      chemically induced by administering ethylnitrosourea (ENU) to pregnant rats, the
      progeny of which developed brain tumors that subsequently were propagated in
      vitro and cloned. They are either weakly or non-immunogenic and have an invasive
      pattern of growth and uniform lethality, which make them particularly attractive
      models to test new therapeutic modalities. The CNS-1 glioma was induced by
      administering MNU to a Lewis rat. It has an infiltrative pattern of growth and is
      weakly immunogenic, which should make it useful in experimental neuro-oncology.
      Finally, the BT4C glioma was induced by administering ENU to a BD IX rat,
      following which brain cells were propagated in vitro until a tumorigenic clone
      was isolated. This tumor has been used for a variety of studies to evaluate new
      therapeutic modalities. The Avian Sarcoma Virus (ASV) induced tumors, and a
      continuous cell line derived from one of them designated RT-2, have been useful
      for studies in which de novo tumor induction is an important requirement. These
      tumors also are immunogenic and this limits their usefulness for therapy studies.
      It is essential to recognize the limitations of each of the models that have been
      described, and depending upon the nature of the study to be conducted, it is
      important that the appropriate model be selected.

PMID- 19381451
TI  - Improving protein extraction and separation methods for investigating the
      metaproteome of anaerobic benzene communities within sediments.
AB  - BTEX compounds such as benzene are frequent soil and groundwater contaminants
      that are easily biodegraded under oxic conditions by bacteria. In contrast,
      benzene is rather recalcitrant under anaerobic conditions. The analysis of anoxic
      degradation is often hampered by difficult sampling conditions, limited amounts
      of biomass and interference of matrix compounds with proteomic approaches. In
      order to improve the procedure for protein extraction we established a scheme
      consisting of the following steps: dissociation of cells from lava granules, cell
      lysis by ultrasonication and purification of proteins by phenol extraction. The
      2D-gels revealed a resolution of about 240 proteins spots and the spot patterns
      showed strong matrix dependence, but still differences were detectable between
      the metaproteomes obtained after growth on benzene and benzoate. Using direct
      data base search as well as de novo sequencing approaches we were able to
      identify several proteins. An enoyl-CoA hydratase with cross species homology to
      Azoarcus evansii, is known to be involved in the anoxic degradation of
      xenobiotics. Thereby the identification confirmed that this procedure has the
      capacity to analyse the metaproteome of an anoxic living microbial community.

PMID- 19381452
TI  - Purification and characterization of an efficient poultry feather degrading
      protease from Myrothecium verrucaria.
AB  - The purpose of this work was to characterize an alkaline protease from the
      filamentous fungus Myrothecium verrucaria and to explore its capability to
      degrade native poultry feathers. The enzyme was purified to homogeneity using a
      single chromatographic step. Recovery was high, 62%, with a specific activity of
      12,851.8 U/mg protein. The enzyme is a small monomeric protein with a molecular
      mass of 22 +/- 1.5 kDa. It presented pH optimum of 8.3 and was stable over a
      broad pH range (5.0-12.0). The temperature optimum was 37 degrees C, with thermal
      stability at temperatures up to 45 degrees C. The enzyme presented an efficiency
      of 80.3% in the degradation of poultry feather meal, releasing amino acids and
      soluble peptides. It was able to hydrolyze beta-keratin without necessity of
      chemical or enzymatic reduction of the disulphide bonds. Considering that,
      everyday, poultry-processing plants produce feathers as a waste products, this
      protease can be useful in biotechnological processes aiming to improve the
      transformation of poultry feathers through solubilization of beta-keratin into
      usable peptides. Furthermore, it can also be useful in processes aiming to reduce
      the environmental pollution caused by the accumulation of feathers.

PMID- 19381453
TI  - Serosal inflammation (pleural and pericardial effusions) related to tyrosine
      kinase inhibitors.
AB  - Tyrosine kinase inhibitors (TKIs) have dramatically changed the treatment of
      chronic myeloid leukemia (CML) and are increasingly used in other malignancies.
      Despite the apparent selectivity of these agents significant side effects can
      occur mainly due to off target kinase inhibition. Clinical consequences of
      serosal inflammation, including pleural and pericardial effusions, have emerged
      as a frequent adverse event associated with dasatinib while occurring much less
      frequently during imatinib and nilotinib therapy. The pathogenesis is uncertain
      but may involve inhibition of platelet derived growth factor or expansion of
      cytotoxic T and natural killer cells. The development of serosal inflammation
      with dasatinib poses a significant challenge to physicians, as it cannot be
      predicted, the time of onset is variable, and management frequently requires
      repeat invasive procedures.

PMID- 19381454
TI  - The emerging safety profile of mTOR inhibitors, a novel class of anticancer
      agents.
AB  - Mammalian target of rapamycin (mTOR) has emerged as an important target for
      cancer therapy. Rapamycin has a distinct, well-documented toxicity profile and
      most of the toxicity data has been reported in patients with organ
      transplantation. Newer mTOR inhibitors have slightly different pharmacokinetic
      properties, yet they present toxicity profiles similar to rapamycin. Most of
      these toxicities are mild to moderate in severity and can be managed clinically
      by dose modification and supportive measures. Mucositis and pneumonitis are the
      most commonly reported toxicities, but they rarely lead to treatment
      discontinuation. Pathogenesis of pneumonitis is uncertain, but various hypotheses
      have been suggested, including cell-mediated immune response to the drug.

PMID- 19381455
TI  - Capsaicin induces apoptosis by generating reactive oxygen species and disrupting
      mitochondrial transmembrane potential in human colon cancer cell lines.
AB  - Although genetic factors are a well-known cause of colorectal cancer,
      environmental factors contribute more to its development. Despite advances in the
      fields of surgery, radiotherapy and chemotherapy, the cure rates for colon cancer
      have not substantially improved over the past few decades. Capsaicin (trans-8
      methyl-N-vanillyl-6-nonenamide), the principal pungent ingredient of hot chili
      pepper, has exhibited an anti-tumor effect in many cell types. However, the
      mechanisms responsible for the anti-tumor effect of capsaicin are not yet
      completely understood. In this study, we investigated whether capsaicin induces
      apoptosis in colon cancer cell lines. Capsaicin decreased cell viability in a
      dose-dependent manner in Colo320DM and LoVo cells. In addition, capsaicin
      produced cell morphology changes and DNA fragmentation, decreased the DNA
      contents, and induced phosphatidylserine translocation, which is a hallmark of
      apoptotic cell death. We showed that capsaicin-induced apoptosis is associated
      with an increase in ROS generation and a disruption of the mitochondrial
      transmenbrane potential. A possible mechanism of capsaicin-induced apoptosis is
      the activation of caspase 3, a major apoptosis-executing enzyme. Treatment with
      capsaicin induced a dramatic increase in caspase 3 activity, as assessed by the
      cleavage of Ac-DEVD-AMC, a fluorogenic substrate. In conclusion, our results
      clearly showed that capsaicin induced apoptosis in colon cancer cells. Although
      the actual mechanisms of capsaicin-induced apoptosis remain uncertain, it may be
      a beneficial agent for colon cancer treatment and chemoprevention.

PMID- 19381456
TI  - Molecular epigenetics: dawn of a new era of biomedical research.

PMID- 19381457
TI  - Epigenetic regulation: methylation of histone and non-histone proteins.
AB  - Histone methylation is believed to play important roles in epigenetic memory in
      various biological processes. However, questions like whether the methylation
      marks themselves are faithfully transmitted into daughter cells and through what
      mechanisms are currently under active investigation. Previously, methylation was
      considered to be irreversible, but the recent discovery of histone lysine
      demethylases revealed a dynamic nature of histone methylation regulation on four
      of the main sites of methylation on histone H3 and H4 tails (H3K4, H3K9, H3K27
      and H3K36). Even so, it is still unclear whether demethylases specific for the
      remaining two sites, H3K79 and H4K20, exist. Furthermore, besides histone
      proteins, the lysine methylation and demethylation also occur on non-histone
      proteins, which are probably subjected to similar regulation as histones. This
      review discusses recent progresses in protein lysine methylation regulation
      focusing on the above topics, while referring readers to a number of recent
      reviews for the biochemistry and biology of these enzymes.

PMID- 19381458
TI  - MicroRNAs - powerful repression comes from small RNAs.
AB  - microRNAs (miRNAs) encode a novel class of small, non-coding RNAs that regulate
      gene expression post-trancriptionally. miRNAs comprise one of the major non
      coding RNA families, whose diverse biological functions and unusual capacity for
      gene regulation have attracted enormous interests in the RNA world. Over the past
      16 years, genetic, biochemical and computational approaches have greatly shaped
      the growth of the field, leading to the identification of thousands of miRNA
      genes in nearly all metazoans. The key molecular machinery for miRNA biogenesis
      and silencing has been identified, yet the precise biochemical and regulatory
      mechanisms still remain elusive. However, recent findings have shed new light on
      how miRNAs are generated and how they function to repress gene expression. miRNAs
      provide a paradigm for endogenous small RNAs that mediate gene silencing at a
      genome-wide level. The gene silencing mediated by these small RNAs constitutes a
      major component of gene regulation during various developmental and physiological
      processes. The accumulating knowledge about their biogenesis and gene silencing
      mechanism will add a new dimension to our understanding about the complex gene
      regulatory networks.

PMID- 19381460
TI  - Transcriptional regulation of the Herpes Simplex Virus 1alpha-gene by the viral
      immediate-early protein ICP22 in association with VP16.
AB  - Herpes Simplex Virus 1 (HSV1) is capable of inducing two forms of infection in
      individuals, and the establishment of which type of infection occurs is linked to
      the transcriptional activation of viral alpha genes. One of the HSV1 alpha genes,
      ICP22, is known to have multiple functions during virus replication, but its
      distinct roles are still unclear. This study showed that ICP22 functions as a
      general repressor for certain viral and cellular promoters, and this
      transcriptional repression by ICP22 is independent of the specific upstream
      promoter element, as shown using the CAT enzyme assay system. Further work also
      found that VP16 interfered with ICP22 mediated transcriptional repression of the
      viral alpha4 gene, through interactions with specific elements upstream of the
      alpha4 gene promoter. These findings support the possibility that ICP22 and VP16
      control transcription of HSV1alpha genes in a common pathway for the
      establishment of either viral lytic or latent infections.

PMID- 19381459
TI  - RNA-directed DNA methylation and demethylation in plants.
AB  - RNA-directed DNA methylation (RdDM) is a nuclear process in which small
      interfering RNAs (siRNAs) direct the cytosine methylation of DNA sequences that
      are complementary to the siRNAs. In plants, double stranded-RNAs (dsRNAs)
      generated by RNA-dependent RNA polymerase 2 (RDR2) serve as precursors for Dicer
      like 3 dependent biogenesis of 24-nt siRNAs. Plant specific RNA polymerase IV
      (Pol IV) is presumed to generate the initial RNA transcripts that are substrates
      for RDR2. siRNAs are loaded onto an argonaute4-containing RISC (RNA-induced
      silencing complex) that targets the de novo DNA methyltransferase DRM2 to RdDM
      target loci. Nascent RNA transcripts from the target loci are generated by
      another plant-specific RNA polymerase, Pol V, and these transcripts help recruit
      complementary siRNAs and the associated RdDM effector complex to the target loci
      in a transcription-coupled DNA methylation process. Small RNA binding proteins
      such as ROS3 may direct target-specific DNA demethylation by the ROS1 family of
      DNA demethylases. Chromatin remodeling enzymes and histone modifying enzymes also
      participate in DNA methylation and possibly demethylation. One of the well
      studied functions of RdDM is transposon silencing and genome stability. In
      addition, RdDM is important for paramutation, imprinting, gene regulation, and
      plant development. Locus-specific DNA methylation and demethylation, and
      transposon activation under abiotic stresses suggest that RdDM is also important
      in stress responses of plants. Further studies will help illuminate the functions
      of RdDM in the dynamic control of epigenomes during development and environmental
      stress responses.

PMID- 19381461
TI  - CENP-K and CENP-H may form coiled-coils in the kinetochores.
AB  - Kinetochores are large proteinaceous structure on the surface of chromosomes'
      primary constriction during mitosis. They link chromosomes to spindle
      microtubules and also regulate the spindle assembly checkpoint, which is crucial
      for correct chromosome segregation in all eukaryotes. The better known core
      networks of kinetochores include the KMN network (K, KNL1; M, Mis12 complex; N,
      Ndc80 complex)and CCAN (constitutive centromere-associated network). However, the
      detailed molecular mechanism of the kinetochore protein network remains unclear.
      This study demonstrates that CENP-H and CENP-K form quite stable subcomplex by
      TAP (tandem affinity purification) with HEK 293 cells which express TAP-CENP-K,
      with the ratio of purified CENP-H and CENP-K being close to 1: 1 even with high
      salt. Bioinformatic analysis suggests that CENP-H and CENP-K are enriched with
      coiled-coil regions. This implies that CENP-H and CENP-K form heterodimeric
      coiled-coils. Furthermore, the functional regions which form the complex are
      respectively located on their N- and C-terminals, but the association between the
      C-terminals is more complex. It is possible that this is the first identified
      heterodimeric coiled-coils within the inner kinetochore, which is directly
      involved in the attachment between kinetochores and the spindle microtubules.

PMID- 19381462
TI  - Endothelin-1 induces intracellular [Ca2+] increase via Ca 2+ influx through the L
      type Ca2+ channel, Ca 2+ -induced Ca2+ release and a pathway involving ET A
      receptors, PKC, PKA and AT1 receptors in cardiomyocytes.
AB  - Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp
      techniques, we found that endothelin-1 (ET-1) significantly elevated the
      intracellular calcium level ([Ca(2+)](i)) in a dose-dependent manner and
      activated the L-type Ca(2+) channel in cardiomyocytes isolated from rats. The
      effect of ET-1 on [Ca(2+)](i) elevation was abolished in the presence of the
      ET(A) receptor blocker BQ123, but was not affected by the ET(B) receptor blocker
      BQ788. ET-1-induced an increase in [Ca(2+)](i), which was inhibited 46.7% by
      pretreatment with a high concentration of ryanodine (10 micromol/L), a blocker of
      the ryanodine receptor. The ET-1-induced [Ca(2+)](i) increase was also inhibited
      by the inhibitors of protein kinase A (PKA), protein kinase C (PKC) and
      angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an
      enhancement of the amplitude of the whole cell L-type Ca(2+) channel current and
      an increase of open-state probability (NPo) of an L-type single Ca(2+) channel.
      BQ123 completely blocked the ET-1-induced increase in calcium channel open-state
      probability. In this study we demonstrated that ET-1 regulates calcium overload
      through a series of mechanisms that include L-type Ca(2+) channel activation and
      Ca(2+)-induced Ca(2+) release (CICR). ETA receptors, PKC, PKA and AT1 receptors
      may also contribute to this pathway.

PMID- 19381464
TI  - Arginine bi-directional translocation and breakdown into ornithine along the
      arbuscular mycorrhizal mycelium.
AB  - Bi-directional translocation and degradation of Arginine (Arg) along the
      arbuscular mycorrhizal (AM) fungal mycelium were testified through (15)N and/or
      (13)C isotopic labeling. In vitro mycorrhizas of Glomus intraradices and Ri T-DNA
      transformed carrot roots were grown in dual compartment Petri dishes. [(15)N-
      and/or(13)C]Arg was supplied to either the fungal compartment or the mycorrhizal
      compartment or separate dishes containing the uncolonized roots. The levels and
      labeling of free amino acids (AAs) in the mycorrhizal roots and in the
      extraradical mycelia(ERM) were measured by gas chromatography/mass spectrometry
      (GC-MS) and high-performance liquid chromatography (HPLC). The ERM of AM fungi
      exposed in either NH(4) (+) or urea as sole external nitrogen source had much
      higher (15)N enrichment of Arg, compared with those in nitrate or exogenous Arg;
      however, glycerol supplied as an external carbon source to the ERM had no
      significant effect on the level of Arg in the ERM. Meanwhile, Arg biosynthesized
      in the ERM could be translocated intact to the mycorrhizal roots and thereby the
      level of Arg in the mycorrhizal roots increased to about 20% after culture of ERM
      in 4 mmol/L NH(4) (+) for 6 weeks. Also Arg was found to be bi-directionally
      transported along the AM fungal mycelium through [U-(13)C]Arg labeling either in
      the mycorrhizal compartment or in the fungal compartment. Once Arg was
      translocated to the potential N-limited sites, it would be further degraded into
      ornithine (Orn) and urea since either [U-(13)C] or [U-(15)N/U-(13)C]Orn was
      apparently shown up in the mycorrhizal root tissues when [U-(13)C] or [U-(15)N/U
      (13)C]Arg was labeled in the fungal compartment, respectively. Evidently Orn
      formation indicated the ongoing activities of Arg translocation and degradation
      through the urea cycle in AM fungal mycelium.

PMID- 19381463
TI  - Protein identification and mRNA analysis of phytochrome-regulated genes in
      Arabidopsis under red light.
AB  - Phytochromes are a family of plant photoreceptors that mediate physiological and
      developmental responses to red and far-red light. According to the affymetrix
      ATH1 microarray, phytochrome A (phyA) and phytochrome B (phyB) together play a
      key role in transducing the Rc signals to light-responsive genes. In order to
      select those red light-responsive genes associated with phyA or phyB, a proteomic
      approach based on two-dimensional gel electrophoresis (2-DE) was used to compare
      the protein expression patterns of the phyAphyB double mutant and the wild type
      of Arabidopsis thaliana (col-4) which grew under constant red light conditions
      for 7 d. Thirty-two protein spots which exhibited differences in protein
      abundance were identified by matrix-assisted laser desorption/ionization-time of
      flight/time of flight mass spectrometry. The expression of ten genes
      corresponding to ten protein spots was analyzed by a semiquantitative reverse
      transcription-polymerase chain reaction. Two of the ten genes were confirmed by
      quantitative PCR (Q-PCR). The results showed that phytochromes may exert their
      function by regulating mRNA or protein expressions. Proteomic analysis may
      provide a novel pathway for identifying phytochrome-dependent genes.

PMID- 19381465
TI  - Production of transgenic cashmere goat embryos expressing red fluorescent protein
      and containing IGF1 hair-follicle-cell specific expression cassette by somatic
      cell nuclear transfer.
AB  - In the present study, cashmere goat fetal fibroblasts were transfected with pCDsR
      KI, a hair-follicle-cell specific expression vector for insulin-like growth
      factor 1 (IGF1) that contains two markers for selection (red fluorescent protein
      gene and neomycin resistant gene). The transgenic fibroblasts cell lines were
      obtained after G418 selection. Prior to the somatic cell nuclear transfer (SCNT),
      the maturation rate of caprine cumulus oocytes complexes (COCs) was optimized to
      an in vitro maturation time of 18 h. Parthenogenetic ooctyes were used as a model
      to investigate the effect of two activation methods, one with calcium ionophore
      IA23187 plus 6-DMAP and the other with ethanol plus 6-DMAP. The cleavage rates
      after 48 h were respectively 88.7% and 86.4%, with no significant difference
      (P>0.05). There was no significant difference between the cleavage rate and the
      blastocyst rate in two different media (SO-Faa and CR1aa; 86.3% vs 83.9%, P>0.05
      and 23.1% vs 17.2%, P>0.05). The fusion rate of a 190 V/mm group (62.4%) was
      significantly higher than 130 V/mm (32.8%) and 200 V/mm (42.9%), groups (P>0.05).
      After transgenic somatic cell nuclear transfer (TSCNT) manipulation, 203
      reconstructed embryos were obtained in which the cleavage rate after in vitro
      development (IVD) for 48 h was 79.3% (161/203). The blastocyst rate after IVD for
      7 to 9 d was 15.3% (31/203). There were 17 embryos out of 31 strongly expressing
      red fluorescence. Two of the red fluorescent blastocysts were randomly selected
      to identify transgene by polymerase chain reaction. Both were positive. These
      results showed that: (i) RFP and Neo ( r ) genes were correctly expressed
      indicating that transgenic somatic cell lines and positive transgenic embryos
      were obtained; (ii) one more selection at the blastocyst stage was necessary
      although the donor cells were transgenic positive, because only partially
      transgenic embryos expressing red fluorescence were obtained; and (iii) through
      TSCNT manipulation and optimization, transgenic cashmere goat embryos expressing
      red fluorescence and containing an IGF1 expression cassette were obtained, which
      was sufficient for production of transgenic cashmere goats.

PMID- 19381466
TI  - Identifying drug-target proteins based on network features.
AB  - Proteins rarely function in isolation inside and outside cells, but operate as
      part of a highly interconnected cellular network called the interaction network.
      Therefore, the analysis of the properties of drug-target proteins in the
      biological network is especially helpful for understanding the mechanism of drug
      action in terms of informatics. At present, no detailed characterization and
      description of the topological features of drug-target proteins have been
      available in the human protein-protein interaction network. In this work, by
      mapping the drug-targets in DrugBank onto the interaction network of human
      proteins, five topological indices of drug-targets were analyzed and compared
      with those of the whole protein interactome set and the non-drug-target set. The
      experimental results showed that drug-target proteins have higher connectivity
      and quicker communication with each other in the PPI network. Based on these
      features, all proteins in the interaction network were ranked. The results showed
      that, of the top 100 proteins, 48 are covered by DrugBank; of the remaining 52
      proteins, 9 are drug-target proteins covered by the TTD, Matador and other
      databases, while others have been demonstrated to be drug-target proteins in the
      literature.

PMID- 19381467
TI  - [Merkel cell carcinoma].
AB  - A 67-year old patient developed multiple flesh-colored nodules on the back of his
      left hand. Histological examination led to the diagnosis of a Merkel cell
      carcinoma (MCC). This highly aggressive primary cutaneous tumor is classified as
      a neuroendocrine carcinoma. It affects mostly elderly and immunosuppressed
      patients. Recently, a new polyomavirus (MCPyV) has been detected in about 75-85%
      of MCC and seems to play an important role in their pathogenesis. This new
      finding may help to develop new therapeutic options for MCC.

PMID- 19381468
TI  - [A new visualization device for ENT surgery : the panoramic visualization system
      (HD-PVS)].
AB  - BACKGROUND: This work examines the application possibilities of the panoramic
      visualization system (HD-PVS) in ENT surgery. The HD-PVS is a new optical system
      that is neither an endoscope nor a microscope. It has a focal length of 200 mm
      and a wide field of view. PATIENT AND METHODS: The analysis of the visualization
      quality took place under laboratory conditions at 4 close-to-surgery scenarios
      with a total of 40 result values. Furthermore, the system was used for 45
      operative procedures on patients (tympanoplasty, parotidectomy, neck dissection,
      septumplasty, transfacial approaches). The results were analyzed following the
      ICCAS workflow-scheme and with standardized questionnaires. RESULTS: The analysis
      of the visualization quality of the PVS exhibited the best total evaluation in 2
      out of 4 scenarios, in 1 scenario HD-PVS attained the maximum score possible, as
      did the microscope and the endoscope was better than HD-PVS in 1 scenario. The
      microscope was never evaluated as being better than HD-PVS. Apart from its use in
      middle ear surgery, the HD-PVS can be considered operational in 4 out of 5
      clinical applications with only slight modifications. CONSEQUENCES: The
      advantages of HD-PVS over gold standards such as the surgical microscope are
      lower initial costs for the optical system with frequently already existing HD
      video system, smaller space requirements, equal or sometimes better visualization
      quality, possibility of videoendoscopic representation of surgery and better
      ergonomic conditions.

PMID- 19381469
TI  - Deregulation of acetohydroxy-acid synthase: Loss of allosteric inhibition
      conferred by mutations in the catalytic subunit.
AB  - Acetohydroxy-acid synthases (AHAS) of two mutant strains Streptomyces
      cinnamonensis ACB-NLR-2 and BVR-18 were chosen for this study for their apparent
      activation by valine, which regularly acts as an allosteric inhibitor. Sequencing
      the ilvB genes coding for the AHAS catalytic subunit revealed two distant changes
      in the mutants, DeltaQ217 and E139A, respectively. Homology modeling was used to
      propose the structural changes caused by those mutations. In the mutant strain
      ACB-NLR-2 (resistant to 2-amino-3-chlorobutyrate and norleucine), deletion of
      Q217 affected a helix in ss-domain, distant from the active center. As no
      mutation was found in the regulatory subunit of this strain, DeltaQ217 in IlvB
      was supposed to be responsible for the observed valine activation, probably via
      changed properties on the proposed regulatory-catalytic subunit interface. In
      mutant strain BVR-18 (resistant to 2-oxobutyrate), substitution E139A occurred in
      a conservative loop near the active center. In vitro AHAS activity assay with the
      enzyme reconstituted from the wild-type regulatory and BVR-18 catalytic subunits
      proved that the substitution in the catalytic subunit led to the apparent
      activation of AHAS by valine. We suggest that the conservative loop participated
      in a conformational change transfer to the active center during the allosteric
      regulation.

PMID- 19381470
TI  - Geographical distribution of genotypic and phenotypic markers among Bacillus
      anthracis isolates and related species by historical movement and horizontal
      transfer.
AB  - The geographical distribution of Bacillus anthracis strains and isolates bearing
      some of the same genetic markers as the Amerithrax Ames isolate was examined and
      evaluated. At least one mechanism for the horizontal movement of genetic markers
      was shown amongst isolates and closely related species and the effect of such
      mixing was demonstrated on phenotype. The results provided potential mechanisms
      by which attempts to attribute isolates of Bacillus anthracis to certain
      geographical and isolate sources may be disrupted.

PMID- 19381471
TI  - Implication of Dichomitus squalens manganese-dependent peroxidase in dye
      decolorization and cooperation of the enzyme with laccase.
AB  - Three new chromatographic forms of Dichomitus squalens manganese-dependent
      peroxidase (MnP) were isolated from wheat-straw cultures using Mono Q and
      connective interaction media (CIM) fast protein liquid chromatography. Enzymes
      revealed identical molar mass of 50 kDa (estimated by SDS-PAGE) and pI values of
      3.5, however, they varied in Km values obtained for Mn2+ oxidation. The addition
      of wood and straw methanol extracts to the cultures showed that the production of
      MnPs in wheat-straw cultures was influenced rather by the type of cultivation
      than by phenolic compounds from lignocellulosic material which induced laccase
      production. The purified CIM1 MnP was able to decolorize selected azo and
      anthraquinone dyes more rapidly than laccase Lc1. In vitro dye decolorization
      showed a synergistic cooperation of MnP and laccase. In the case of CSB
      degradation MnP prevented from the production of a differently colored substance
      that could be produced after CSB degradation by laccase-HBT system.

PMID- 19381472
TI  - Molecular characterization of intervening sequences in 23S rRNA genes and 23S
      rRNA fragmentation in Taylorella equigenitalis.
AB  - Using two primer pairs constructed in silico for the amplification of the
      intervening sequences (IVSs) of the 23S rRNA gene sequences of the genus
      Taylorella, none of the three representative T. equigenitalis strains
      NCTC11184(T), Kentucky 188 and EQ59 was shown to contain any IVSs in the first
      quarter region. In the central region, all three strains possessed one
      approximately 70 bp IVS (TeIVS2) different from any IVSs found in T.
      asinigenitalis. The predicted secondary structure model of the IVSs contained
      stem and loop structures. The central region of the IVS-stem structure contains
      an identical double-stranded consensus 15-bp sequence. The purified RNA fraction
      from the three strains contained 16S and 4-5S RNA species but no 23S rRNA
      species. Thus, the primary 23S rRNA transcripts from the three strains would be
      cleaved into approximately 1.2- and 1.6-kb rRNA fragments and approximately 70-bp
      IVS. In addition, 16 other T. equigenitalis isolates were found to carry a
      similar 70-bp IVS in the central region and to produce fragmented 23S rRNA.

PMID- 19381473
TI  - Serological and molecular detection of Borrelia burgdorferi sensu lato and
      Anaplasmataceae in rodents.
AB  - The presence of Anaplasma spp. and Borrelia burgdorferi sensu lato in rodents
      from Eastern Slovakia were followed by serological and molecular methods. The
      seroprevalence for Borrelia was detected in 16.6 %, for Anaplasmataceae (APT) in
      13.2 % and co-occurrence of Borrelia and APT in 7.5 %. Out of 110 ear biopsies of
      rodents, 5 were B. afzelii-positive. Five biopsies tested positive with the
      Ehr521-Ehr747 primers amplifying all the members of the family APT. A.
      phagocytophilum was detected in 1.8 %, 2.7 % were infected with Anaplasma-like
      organisms. Co-occurrence of Borrelia and Anaplasma in ear biopsies was found in
      1.8 %. The circulation of both Borrelia and Anaplasma in the region of Eastern
      Slovakia was confirmed.

PMID- 19381474
TI  - The biofilm-positive Staphylococcus epidermidis isolates in raw materials,
      foodstuffs and on contact surfaces in processing plants.
AB  - Isolates from the "farm to fork" samples (182 isolates from 2779 samples) were
      examined genotypically (icaAB genes) and phenotypically (in vitro biofilm
      formation, typical growth on Congo red agar; CRA) with the aim to assess the risk
      of penetration of virulent strains of Staphylococcus epidermidis into the food
      chain. The contamination of meat and milk products was significantly higher in
      comparison with raw materials. Contamination of contact surfaces in the meat
      processing plants was significantly lower than that of contact surfaces in the
      dairy plants. The ica genes (which precondition the biofilm formation) were
      concurrently detected in 20 isolates that also showed a typical growth on CRA.
      Two ica operon-negative isolates produced biofilm in vitro but perhaps by an ica
      independent mechanism. The surfaces in the dairy plants and the milk products
      were more frequently contaminated with ica operon-positive strains (2.3 and 1.2 %
      samples) than the other sample types (0-0.6 % samples).

PMID- 19381475
TI  - Acetaldehyde stimulates ethanol-stressed Saccharomyces cerevisiae, grown on
      various carbon sources.
AB  - The ability of added acetaldehyde to stimulate growth in ethanol-stressed
      Saccharomyces cerevisiae while grown on non-fermentable substrates (ethanol,
      glycerol) is reported. The addition of acetaldehyde to ethanol-stressed yeast
      grown on either ethanol or glycerol led to a significant decrease in lag time of
      67 and 45 %, respectively (p = 0.000) and an increase in the specific growth rate
      (0.008-0.038/h and 0.060-0.074/h, respectively). The stimulatory effect of
      acetaldehyde could be mimicked by the addition of propionaldehyde. Results,
      following metabolic tracing of the added stimulants, question the previously held
      notion that the acetaldehyde effect in S. cerevisiae is fully redox related.

PMID- 19381476
TI  - Purification and biochemical characterization of thermostable alkaline
      phosphatases produced by Rhizopus microsporus var. rhizopodiformis.
AB  - The biochemical properties of the alkaline phosphatases (AlPs) produced by
      Rhizopus microsporus are described. High enzymic levels were produced within 1-2
      d in agitated cultures with 1 % wheat bran. Intra- and extracellular AlPs were
      purified 5.0 and 9.3x, respectively, by DEAE-cellulose and ConA-sepharose
      chromatography. Molar mass of 118 and 120 kDa was estimated by gel filtration for
      both forms of phosphatases. SDS-PAGE indicated dimeric structures of 57 kDa for
      both forms. Mn(2+), Na(+) and Mg(2+) stimulated the activity, while Al(3+) and
      Zn(2+) activated only the extracellular form. Optimum temperature and pH for both
      phosphatases were 65 degrees C and pH 8.0, respectively. The enzymes were stable
      at 50 degrees C for at least 15 min. Hydrolysis of 4-nitrophenyl phosphate
      exhibited a K (m) 0.28 and 0.22 mmol/L, with upsilon (lim) 5.89 and 4.84 U/mg,
      for intra- and extracellular phosphatases, respectively. The properties of the
      reported AlPs may be suitable for biotechnological application.

PMID- 19381477
TI  - The selection of single-chain Fv antibody fragments specific to Bhlp 29.7 protein
      of Brachyspira hyodysenteriae.
AB  - Single-chain antibodies (scFv) specific to Brachyspira hyodysenteriae were
      isolated from a phagemid library. Recombinant Bhlp 29.7 protein was used for scFv
      selection and individual clones were tested by ELISA and immunofluorescent test;
      four unique clones were isolated. One of selected clones was able to bind
      specifically B. hyodysenteriae in ELISA and immunofluorescence test. This is the
      first report of species-specific recombinant antibodies against B.
      hyodysenteriae.

PMID- 19381478
TI  - Staphylococcus cohnii hemolysins - isolation, purification and properties.
AB  - A total 355 of Staphylococcus cohnii isolates from hospital environment, patients
      (newborns), medical staff and from non-hospital environment were tested for
      hemolytic activity. Ninety-one % of S. cohnii ssp. cohnii and 74.5 % S. cohnii
      ssp. urealyticus strains exhibited hemolysis synergistic to S. aureus ATCC 25923
      strain. Crude preparations of hemolysins of both bacterial subspecies presented
      delta-hemolysin, but not alpha- and beta-toxin activity. Highly pure hemolysins
      were obtained by semipreparative SDS-PAGE or by organic solvent extraction from
      the freeze-dried crude preparations. Native-PAGE and 2D-PAGE showed their high
      heterogeneity. Molar masses of single hemolysin units estimated by the Tris
      Tricine-SDS-PAGE were calculated as 3.47 kDa for S. cohnii ssp. cohnii and 3.53
      kDa for S. cohnii ssp. urealyticus.

PMID- 19381479
TI  - A new method of optical detection of yeast acidification power.
AB  - We describe here a newly developed method for a contact-free optical pH
      measurement in yeast suspensions supplemented with glucose, and containing the pH
      sensitive triphenylmethane dye bromocresol green. It is suitable for performing
      the acidification power test (based on measuring the rate of pH drop of yeast
      suspension caused by active extrusion of acidity from cells after glucose
      addition) used for assessing yeast vitality in fermentation industries. Using
      this methodology we monitored the pH in yeast suspensions in the course of
      acidification in the pH range of 3.5-5.3. Optical pH measurement allows
      simultaneous testing of several samples, minimizes the sample volume, simplifies
      sample handling and reduces the hands-on time in sample processing.

PMID- 19381480
TI  - Long-term maintenance of fungal cultures on perlite in cryovials - an alternative
      for agar slants.
AB  - Cultures of 33 basidiomycete strains out of 35 tested were viable with unchanged
      characteristics after four years of maintenance on perlite in cryovials. These
      cultures can be a good substitute for agar cultures in long-term maintenance of
      fungi. For comparison, the storage under oil was evaluated but it turned out to
      be unsuitable for the majority of our cultures.

PMID- 19381481
TI  - Autofluorescence of the fruiting body of the fungus Macrolepiota rhacodes.
AB  - The autofluorescence (primary fluorescence, AF) of the freshly collected fruiting
      bodies of the fungus Macrolepiota rhacodes was studied in a Zeiss Jenalumar
      fluorescence microscope at a blue and a green excitation. The strongest yellow AF
      at blue excitation was displayed by irregular granules on the surface of the
      fungal pileus. A weaker yellow-green AF was exhibited by spherical cells and
      hyphae in the central part of the pileus while basidiospores emitted somewhat
      stronger AF. At green excitation, a considerable red AF was emitted only by
      basidiospores, other parts of the pileus showing a very weak red AF. M. rhacodes
      AF is much weaker than the AF of wood-rotting fungi, such as Fomes fomentarius,
      Daedalea quercina, Piptoporus betulinus, Fomitopsis pinicola and others.

PMID- 19381482
TI  - Molecular epidemiology of Pseudomonas aeruginosa clinical isolates from
      Portuguese Central Hospital.
AB  - The relatedness between clinical isolates of P. aeruginosa obtained from patients
      during their stay in a Portuguese Central Hospital was evaluated. Genotypic
      fingerprinting (M13-PCR), phenotypic methods (biotyping and antibiotyping) and
      epidemiological information (spatial and temporal links) were used to evaluate
      the relatedness between 88 clinical isolates (68 patients), selected randomly out
      of 189. Sixty-two M13 types were found, 12 of them containing isolates from more
      than one patient. Thirty-four antibiotypes were found, as well as a significant
      association (p < 0.05) between epidemic isolates and multiresistance patterns.
      The nosocomial transmission of P. aeruginosa strains may be limited since M13
      typing demonstrated a high degree of diversity among all the isolates, suggesting
      the occurrence of mainly independent infectious episodes. The results show the
      possible occurrence of cross-acquisition, cross-colonization and cross-infection
      and suggest an epidemic population structure for P. aeruginosa in this hospital.

PMID- 19381483
TI  - Wolbachia and bacteriophage WO-B density of Wolbachia A-infected Aedes albopictus
      mosquito.
AB  - Wolbachia are maternally inherited symbiotic bacteria capable of inducing an
      extensive range of reproductive abnormalities in their hosts, including
      cytoplasmic incompatibility (CI). Its density (concentration) is likely to
      influence the penetrance of CI in incompatible crosses. The variations of
      Wolbachia density could also be linked with phage WO density. We determined the
      relative density (relative concentration) of prophage WO orf7 and Wolbachia
      (phage-to-bacteria ratio) during early developmental and adult stages of singly
      infected Aedes albopictus mosquito (Wolbachia A-infected) by using real-time
      quantitative PCR. Phage WO and Wolbachia did not develop at the same rate.
      Relative Wolbachia density (bacteria-to-host ratio) was high later in development
      (adult stages) whilst relative prophage WO density (phage-to-bacteria ratio) was
      low in the adult stages. Furthermore, 12-d-old adults of singly infected female
      mosquito had the highest Wolbachia density. In contrast, the larval stage 4 (L4)
      contained the highest prophage WO-B orf7 density. The association of hosts
      Wolbachia-phage among diverse species is different. Thus, if phage and Wolbachia
      are involved in CI mechanism, the information of this association should be
      acquired for each specific type of organism for future use of population
      replacement or gene drive system.

PMID- 19381484
TI  - Markers of Chlamydia pneumoniae and human cytomegalovirus infection in patients
      with chronic peripheral vascular disease and their relation to inflammation,
      endothelial dysfunction and changes in lipid metabolism.
AB  - Our aim was to detect markers of Chlamydia pneumoniae (CPN) and human
      cytomegalovirus (HCMV) infection in patients with peripheral vascular occlusive
      disease and to follow markers of inflammation, endothelial dysfunction and lipid
      metabolism alteration in patients with active infection. CPN genome was detected
      in 9 (47.4 %) patients by at least one PCR method. Serological markers of acute
      CPN infection were found in 5 (26.3 %) subjects; each of them showed also
      positivity in at least one of the PCR methods. HCMV DNA were detected in 2 (10.5
      %) patients; HCMV-specific antibodies were detected in 14 (73.7 %) subjects,
      however only in IgG subclass. Subjects with HCMV PCR positivity thus showed no
      serological markers of active HCMV infection. Laboratory findings of acute CPN
      infection were associated with increased plasma levels of Lp(a),
      triacylglycerols, atherogenic index of plasma and E-selectin (p < 0.05). No
      significant differences were found in the other markers, including plasma levels
      of total cholesterol, ferritin, homocysteine, oxidized LDL, IL-6, IL-8, IL-18,
      TNF-alpha, soluble forms of VCAM-1 and ICAM-1, von Willebrand factor, C-reactive
      protein, and plasma nitrites & nitrates. Frequent presence of chlamydial DNA in
      atheromatous plaques from patients with peripheral vascular disease was
      confirmed. HCMV DNA was detected only sporadically and with positivity in
      anamnestic anti-HCMV antibodies (IgG) only, indicating a rare presence of latent
      virus rather than active replication. Patients with laboratory markers of acute
      CPN infection exhibited more pronounced alterations in lipid metabolism and
      endothelial dysfunction.

PMID- 19381485
TI  - Expression of IGF-1R and iNOS in nasal polyps; epithelial cell homeostasis and
      innate immune mechanisms in pathogenesis of nasal polyposis.
AB  - Nasal polyps (NP), edematous projections of nasal mucosa (NM), are characterized
      by an inflammatory cellular infiltrate, however, little is known about
      etiopathogenesis of NP. Both innate immune mechanisms leading to activation of NF
      kappaB and homeostasis of epithelial cells were implicated in the pathogenesis of
      NP. In this study we investigated the expression of insulin-like growth factor-1
      receptor (IGF-1R) and inducible nitric-oxide synthase (iNOS) in NP compared to
      healthy NM in both the epithelial and stromal compartments. Using
      immunohistochemistry, frozen tissue sections of NP from 18 patients, and mucosal
      biopsy specimens of the inferior turbinate from 17 subjects were stained for IGF
      1R and iNOS markers. Fluorescence microscopy and computerized image analysis
      revealed low numbers of IGF-1R-positive cells in all specimens. However,
      substantially increased numbers of IGF-1R-positive cells were found in NP
      compared to NM both within the epithelium (1.63 vs. 0.43) and stroma (3.27 vs.
      1.03). Positivity for iNOS was detected within the epithelium of NP compared with
      NM. Numbers of iNOS-positive single cells were highly increased in NP vs. NM in
      both epithelial (3.83 vs. 1.08) and stromal (4.96 vs. 2.67) compartments. An
      increased iNOS expression within the epithelial layer as well as increased number
      of iNOS- and IGF-1R-positive cells in NP was observed. This suggests that innate
      immune mechanism, and to a lesser extent also growth and homeostasis of
      epithelial cells, may play a role in formation of NP.

PMID- 19381486
TI  - Seroprevalence of Coxiella burnetii antibodies among students of the Faculty of
      Medicine in Kosice (Slovakia).
AB  - Titers of immunoglobulin IgG against phases I and II of Coxiella burnetii were
      determined in 241 students of the Faculty of Medicine by ELISA method and the
      respective risk factors were evaluated, e.g., rural and urban life, consumption
      of milk, contact with animals and gender, which may be associated with exposure
      to C. burnetii. Phase I antibodies (Abs) were detected in 59 serum samples (24.4
      %) at antibody level of 1: 100-1: 400. Phase II Abs were found in 179 persons
      (74.2 %). The titers were in the range of 1: 100-1: 1600. The titer > or =1: 800
      of IgG was used as a cut-off level, and was detected only in 20 students (8.2 %).
      No significant difference in the prevalence of Abs was detected either between
      the students living in rural and urban environment (78.8 and 73.2 %,
      respectively) or between males and females (74.0 and 74.7 %, respectively). Abs
      were detected more frequently in raw milk consumers (68.1 %) and in students who
      kept some animals (73.7 %).

PMID- 19381487
TI  - Lactobacillus isolates from weaned piglets' mucosa with inhibitory activity
      against common porcine pathogens.
AB  - Twelve lactobacilli isolates from mucosa of 3-5-week-old weaned pigs were found
      to exert good antimicrobial activity against common porcine pathogens (S. aureus,
      B. cereus, E. coli, C. perfringens). Two of them produced in addition to lactic
      acid also considerable amounts of acetic acid, and 6 of them produced hydrogen
      peroxide and metabolites other than organic acids. Isolates 4/26 and 2/25
      (identified as L. crispatus or L. amylovorus) were inhibitory against most
      strains of S. aureus, B. cereus and E. coli, and especially the strain 4/26
      survived well in simulated gastric and intestinal juice. Diarrhea-causing E. coli
      O8K88H9 Ent(+) was successfully inhibited by the growing culture as well as by
      the catalase-treated and neutralized supernatant of L. reuteri 12/26. Mucin
      degradation and multiple resistance to antibiotics were not observed.

PMID- 19381488
TI  - D-glucose enhanced 5-aminolevulinic acid production in recombinant Escherichia
      coli culture.
AB  - In this study, we introduced a new strategy, feeding D-glucose, to overproduce
      extracellular 5-aminolevulinic acid (ALA) in the recombinant Escherichia coli. We
      investigated that the D-glucose concentration is dependent on extracellular ALA
      production. The results indicated that increasing D-glucose concentration in
      bacteria culture enhanced final cell density and ALA yield and simultaneously
      decreased the activities of ALA synthase (ALAS) and ALA dehydratase (ALAD); then,
      the inhibitory effect of D-glucose on ALAS activity was relieved with the
      metabolism of D-glucose. when 4.0 g/L D-glucose was added at late exponential
      phase; 1.46 g/L ALA was achieved in shaking culture, which is 47% or 109% higher
      than the ALA yields with 30 mM levulinic acid of ALAD inhibitor or no inhibitor.
      In jar fermenter, final extracellular ALA concentration reached 3.1 g/L by
      feeding with D-glucose.

PMID- 19381490
TI  - Influence of infection on iron profile in severely malnourished children.
AB  - OBJECTIVE: To study the iron profile and find out an accurate diagnostic tool
      which reflects iron status in different types of infection in severely
      malnourished children aged 12 months to 71 months. METHODS: Hundred and Eight
      (108) children of whom 72 children were infected and 36 non infected severely
      malnourished children according to WHO criteria in the age group of 12-71 months
      were interrogated. 36 healthy control in the same age group were also
      interrogated. RESULTS: Mean serum iron, total iron binding capacity (TIBC),
      ferritin concentration in normal children were significantly higher (P<0.001)
      than non-infected severely malnourished children. On the other hand mean serum
      ferritin concentration was significantly higher (P<0.001) in infected group than
      non-infected group but still lower than normal. Mean serum TIBC concentration
      significantly reduced in severely malnourished children than normal children but
      no significant difference was observed between non-infected and infected group.
      Mean serum iron, and transferrin saturation were significantly reduced (P<0.05)
      in parasitic infestation. CONCLUSION: Severely malnourished children had reduced
      mean serum iron profile. Parasitic infestation influenced the marked reduction of
      mean serum iron concentration and transferrin saturation level. Mean serum iron
      concentration was reduced in acute respiratory infection(ARI) and parasitic
      infestation than other infections. Serum ferritin concentration was elevated in
      all types of infection as acute phase protein but still lower than normal. So
      Iron, TIBC and Transferin saturation <16% constitute good evidence for iron
      deficiency in both infected and non-infected severely malnourished children.

PMID- 19381491
TI  - Modification of Seldinger technique for introduction of femoral lines in
      newborns.

PMID- 19381493
TI  - Gender bias in utilization of health services in Chandigarh.

PMID- 19381494
TI  - Polio eradication in India: need for caution.

PMID- 19381495
TI  - Outcome in childhood Guillain-Barre syndrome.
AB  - OBJECTIVE: To prospectively assess the outcome of children diagnosed with
      Guillain-Barre syndrome (GBS), followed up for a median duration of 25 months.
      METHODS: Tertiary center, prospective follow up of children with GBS enrolled
      between, Dec 2003 to Sep 2006. Functional recovery was determined at 12 months
      and later using Hughes scale (0-6). Clinical, electrophysiological variables were
      compared between the good outcome (grade 0/1) and bad outcome groups (died or
      functional grade >1). RESULTS: Among 52 children with a median age of five yr
      there was male preponderance (75.4%). Mortality during acute phase was 11.5%
      (6/52). Among the survivors long term data was obtainable in 40 of the 46
      children. At one year follow up 87.5% children had fully recovered or had minimal
      symptoms, beyond one year this rose to 95%. Only 2 among 40 had significant
      symptoms at last follow up (1 grade-2 and 1 grade-3). Factors significantly
      associated with poor outcome were: need for artificial ventilation, inexitable
      nerves on nerve conduction testing and delayed independent walking. CONCLUSION:
      Children needing ventilation have the worst short-term prognosis. However,
      irrespective of severity during acute phase, good long-term recovery can be
      expected in most children.

PMID- 19381496
TI  - An outbreak of rubella in a hilly district of Kangra-Chamba, Himachal Pradesh,
      India, 2006.
AB  - OBJECTIVE: Rubella is a minor disease that often goes unnoticed and seldom
      results in significant morbidity and mortality. However, the infection among
      pregnant women is associated with serious consequences for the fetus. On 5th
      November, 2006, a local community leader reported cases of fever with rash in
      three villages of Chamba district to Shahpur hospital. No death was reported. We
      investigated the outbreak as a suspected outbreak of measles with the objectives
      of confirming diagnosis, estimating the magnitude of outbreak and formulating
      recommendations for control and prevention. METHODS: We defined a case of the
      rubella as occurrence of fever with rash in any resident of these three villages
      between 20th October to 9th December, 2006. We line listed the cases and
      collected information on age, sex, residence, date of onset, symptoms, signs,
      treatment history, traveling history, vaccination status and pregnancy status. We
      described the outbreak by time, place and person characteristics. Sera of a
      sample of case patients were tested for IgM antibodies to measles and later
      rubella viruses. RESULTS: We identified 61 cases in three villages - 39 cases in
      Hattli, 17 in Thulel and 5 in Dramman. The overall attack rate (AR) was 8.7%. Sex
      specific AR for males was 10% and females 7.4%. All case patients were less than
      20 years of age and the attack rate was highest in the age group 11-20 years
      (median age 12 years). The index case was traced in Hattli Bengali slum and
      occurred on 20th October 2006 where majorities (41%) of the cases were reported.
      No pregnant woman was found to be affected. The number of cases peaked on 19th
      November and the last case was reported on 9th December 2006. Of 61 case
      patients, 50 (82%) were immunized against measles while proportions of children
      vaccinated for measles were 96% (672/700) and none of them were immunized against
      rubella (including two (3%) who had MMR immunization privately). Out of six blood
      samples tested, all tested negative for measles IgM antibodies but four were
      positive for IgM antibodies to rubella. Only 36% (22/61) of the cases took the
      treatment from modern system of medicine. CONCLUSION: An outbreak of rubella was
      confirmed and was possibly due to the frequent traveling of Bengali colony
      patients to other areas for selling the food items. We advised the local health
      authorities to provide MMR vaccination to the unexposed and energetic IEC in
      three affected and neighboring villages.

PMID- 19381497
TI  - Reactive haemophagocytic lymphohistiocytosis.
AB  - We present a series of five cases diagnosed and treated as reactive
      haemophagocytic lymphohistiocytosis (HLH) in three tertiary referral centers of
      Kolkata, within a time frame of 3 months. The initial presentations were very
      variable, the most prominent clinical feature being--acute renal failure in the
      first patient, convulsions in the second, encephalopathy the third, marked
      cervical lymphadenopathy in the fourth and polyserositis in the fifth. All had a
      history of prolonged fever preceding admission and hepatosplenomegaly on
      examination. Investigations revealed multi-organ involvement with pancytopenia;
      haemophagocytosis was eventually diagnosed by bone marrow examination. These
      cases highlight the diagnostic challenge posed by infection associated
      haemophagocytosis and the need for maintaining a high index of suspicion to
      promptly diagnose and treat this potentially life threatening condition.

PMID- 19381499
TI  - IMCI approach in tertiary hospitals, India.
AB  - OBJECTIVE: This study was conducted to compare physicians' diagnosis with
      Integrated Management of Childhood Illness (IMCI) algorithm generated diagnosis
      in hospitalized children aged 2-59 months. METHODS: Recruited were patients aged
      2-59 months admitted with one or more IMCI danger signs. IMCI and physician's
      diagnosis were noted and compared. RESULTS: In 222 included subjects, mean
      duration of illness was 9.4 (SD: 16.5) days. Among those with cough or difficult
      breathing, 44 (19.8%) and 66 (29.7%) were diagnosed as either severe pneumonia or
      mild to moderate pneumonia by physicians and IMCI algorithm, respectively (p=
      0.015). Among 146 presenting as fever, 140 (95.9%) were diagnosed as very severe
      febrile disease by the IMCI algorithm, whereas physicians diagnosed these as
      either malaria in 10/146 (6.7%), pyogenic meningitis in 47/146 (32.2%), sepsis in
      31/146 (21.3%), tuberculous meningitis in 17/146 (11.6%), encephalitis in 5/146
      (3.4%), measles in 3/146 (2.1%) or others in 24/146 (16.4%). CONCLUSION: As there
      was a low concordance between physician and IMCI algorithmic diagnosis of
      pneumonia (Kappa value= 0.74, 95% CI: (0.64-0.84)) and since very severe febrile
      disease is not a diagnosis made by the physicians, the IMCI algorithms have to be
      refined for appropriate management of these conditions.

PMID- 19381500
TI  - Preputial adhesions--a misunderstood entity.
AB  - OBJECTIVE: To assess the trends and outcomes in referrals of 'phimosis for
      circumcision' to a tertiary care pediatric surgical department. METHODS: This is
      a prospective study of 100 consecutive children of presumed phimosis referred for
      circumcision. They were assessed and classified by the senior author as having
      either preputial adhesions or phimosis. The patients in the former group
      underwent outpatient preputial adhesiolysis while those in the latter group were
      offered circumcision primarily. All were followed up till resolution. RESULTS:
      All 100 were referred with a non-retractile prepuce and an additional reason -
      preputial ballooning at voiding, dysuria or suspect UTI. Eight (mean age -58
      months, referred for preputial ballooning at voiding -6/8 and dysuria -2/8) had
      phimosis and were primarily offered circumcision. The remaining 92 (mean age - 22
      months, referred for preputial ballooning at voiding -52/92, dysuria -28/92 and
      suspect UTI -12/92) had preputial adhesions. In the latter group, none has a
      documented urinary infection on specific investigations. These 92 underwent
      outpatient preputial adhesiolysis. Seventy three (79 %) required a single
      sitting, 11 (12%) required 2 -4 sittings and 4(4.5%) required 5-8 sittings over a
      follow up period of 1 -24 months (median -3 weeks). 4/92(4.5%) were deemed non
      responders to adhesiolysis and were circumcised later. CONCLUSION: The majority
      of children referred with 'phimosis for circumcision' to this tertiary pediatric
      surgical centre were actually physiologic preputial adhesions that were managed
      with outpatient preputial adhesiolysis. This study underscores a lack of
      awareness amongst referring primary care physicians regarding preputial adhesions
      and the potential for an erroneous diagnosis of phimosis translating into
      unnecessary circumcisions in many young boys.

PMID- 19381501
TI  - Pediatric hospitalizations at two different setting community hospitals in north
      India: implications for regionalization of care.
AB  - OBJECTIVE: To evaluate pediatric hospitalizations at two different setting
      community hospitals in north India, and to understand the implications for
      regionalization of pediatric care in heterogeneous environment of India. METHODS:
      Retrospective review of medical records of children hospitalized at a large and a
      small community hospital catering to population from different social classes but
      in close proximity to each other was carried out. Baseline characteristics and
      diagnosis were recorded, and compared using appropriate statistical tests.
      RESULTS: There were notable differences between the age and morbidity profiles at
      the two study hospitals. Smaller community hospital catered to more young,
      malnourished and sicker children. Morbidity profile comprised of significantly
      more acute gastroenteritis and community-acquired pneumonia at the small
      hospital. In contrast, almost a quarter (24.4%) of children was injured at the
      larger community hospital. Infants and newborns were more at small, while older
      children (>5 yrs) were more at the larger community hospital (p<0.0001).
      CONCLUSION: The conclusion drawn from this study is that significant differences
      exist in age and morbidity profiles between different setting community hospitals
      in north India. There is a need to form a prospective registry of community
      hospitals, which would validate the observations of the present study, and has
      implications for regionalization of specialized pediatric services as well as
      postgraduate training in India.

PMID- 19381502
TI  - Successful treatment of congenital chylothorax using fibrin glue.

PMID- 19381503
TI  - Multicystic dysplastic kidney in children--a need for conservative and long term
      approach.
AB  - OBJECTIVE: We retrospectively studied our cases of Multicystic Dysplastic Kidney
      (MCDK). The review was aimed at identifying the pattern of the disease in Indian
      Scenario and the required management thereof. METHODS: We studied the clinical,
      radiological and nuclear scan findings of 22 patients with unilateral MCDK. They
      were diagnosed and/or treated in our unit from 1999 to 2007. The diagnosis was
      achieved by Ultrasound and further confirmed by DMSA scans. Other ancillary
      investigations like Micturating cystourethrogram were done if indicated. These
      patients were followed and followup investigations consisted of renal ultrasound,
      blood pressure measurement, and urinalysis and blood biochemistry RESULTS: A
      total of 22 patients (18 boys and 4 girls) with unilateral MCDK were investigated
      and followed for a mean period of 41 months. MCDK was detected on antenatal
      ultrasound only in 12(55%) and postnatally in 10(45%) babies. Mean age for
      postnatal diagnosis was 20 months. Follow up ultrasound revealed complete
      involution of MCDK in 3 patients and partial regression in 11 patients. The size
      of dysplastic kidney was unchanged in 4 patients and a further 4 patients
      underwent nephrectomy. Indications of nephrectomy were parental anxiety in 2,
      hypertension in 1 and palpable mass in 1. CONCLUSION: Large proportion (45%) of
      patients in presented series are diagnosed post natally contrary to western world
      where more than 80% are diagnosed antenatally. Uncomplicated isolated MCDK carry
      good prognosis with nephrectomy required in only a few patients. Association with
      other urological anomalies in ipsilateral/contralateral genitourinary tract is
      important to identify as they have worse outcome in terms of ultimate renal
      function. All patients with simple/complex unilateral MCDK should be advised long
      term follow up for the possible development of hypertension and/or hyper
      infiltration injury.

PMID- 19381504
TI  - Serum homocysteine in Indian adolescents.
AB  - OBJECTIVE: To assess serum homocysteine levels and its association with
      conventional risk factors for cardiovascular disease (CVD) in Indian adolescents.
      METHODS: This was a cross-sectional study conducted in tertiary care hospital in
      northern India in apparently healthy adolescents aged 10-19 yr. A pre-designed
      questionnaire was used to assess conventional risk factors. Serum homocysteine
      levels of > or = 12 micromol/L, serum triglycerides > or = 150 mg% and serum
      cholesterol > or = 200 mg% were taken as hyperhomocysteinemia,
      hypertriglyceridemia and hypercholesterolemia, respectively. Serum high-density
      lipoprotein (HDL) > or = 40 mg% was considered protective for CVD. RESULTS: In
      103 subjects, 36.87 % females, mean serum homocysteine level was 11.649 +/-0.416
      micromol/L. Hyperhomocysteinemia was present in 46 (44.6%, 95% CI: 34.965-54.75)
      subjects. Dietary deficiency of vitamin B12 and folic acid, body mass index (BMI)
      > 84(th) percentile and altered lipid profile were associated with
      hyperhomocysteinemia on univariate analysis. After multivariate adjustment for
      BMI and vegetarian diet, low serum HDL (OR: 23.81, 95% CI: 2.86-200; p = 0.003)
      and serum hypertriglyceridemia (OR: 4.17, 95% CI: 1.51-13.51; p = 0.022) had
      independent association with hyperhomocysteinemia. CONCLUSION: Since we have also
      found an association between hyperhomocysteinemia and low serum HDL levels and
      hypertriglyceridemia, which are conventional risk factors for CVD, interventional
      strategies are urgently needed among adolescents for prevention of CVD.

PMID- 19381506
TI  - Efficacy of a synbiotic BIFILAC: questionable study.

PMID- 19381505
TI  - The role of insulin like growth factor (IGF)-1 and IGF-binding protein-3 in
      diagnosis of Growth Hormone Deficiency in short stature children.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of IGF-1 and IGFBP
      3 in diagnosis of short stature children and adolescents in whom Growth Hormone
      Deficiency (GHD) was found. METHODS: In this cross sectional study the referred
      short stature children and adolescents to Namazi Hospital in Shiraz- Iran, in
      2003-2005 were studied. The inclusion criteria were proved short stature based on
      the physical examination, weight, height, standard deviation score (SDS) of
      height < -2, with considering stage of puberty and predicted height in children
      without any genetic or chronic disorders. The exclusion criteria were any
      positive physical or laboratory data suggesting hypothyroidism, rickets or liver
      disorders. For all patients a provocative growth hormone test was performed with
      propranolol and L-dopa and serum IGF-1 and IGFBP-3 were measured. GHD defined as
      peak(cutoff) serum GH level under 10 ig/L and low IGF-1 and IGFBP-3 considered as
      cutoff serum level under -2 standard deviation. RESULTS: Eighty one short stature
      patients (39 boys and 42 girls) with mean age of 10.6 +/- 3.5 years completed the
      study. Seventeen patients with GHD were found and in 18 patients IGF-1 level were
      low. Only in 6 patients both GH and IGF-1 were low and 2 of them had low IGFBP-3.
      There were no correlations between the levels of GH,IGF-1 and IGFBP-3 in children
      with short stature due to GHD. The sensitivity and specifity of IGF-1 and IGFBP-3
      in assessment of GHD were 35% and 81% for IGF-1 and 12% and 94% for IGFBP-3,
      respectively. CONCLUSION: No correlations were found between GH level and serum
      levels of IGF-1 and IGFBP-3 in short patients and the sensitivity of those tests
      in assessment of GHD were poor.

PMID- 19381507
TI  - Assessment of intramuscular injection practices of health workers in urban
      dispensaries.

PMID- 19381508
TI  - Recurrent headache in Indian adolescents.
AB  - OBJECTIVE: To analyze the epidemiology and characteristics of primary recurrent
      headaches in Indian adolescents. METHODS: This cross sectional study was
      conducted in three urban public schools. Adolescents of 9(th) to 12(th) grades
      were included and they were given a questionnaire in their classrooms in the
      presence of at least one of the authors, who assisted them in filling it. They
      were asked to provide responses based on most severe recurrent headache they had
      experienced rather than the more frequent one. Diagnosis was based upon the
      information contained in questionnaire, however, where it was inadequate, those
      subjects were approached telephonically. Statistical analysis was done with the
      help of SPSS v. 11.0. Descriptive analysis, Chi-Square test, Fisher's Exact test,
      and independent sample't' test were run. RESULTS: 2235 adolescents were included
      in the present study (boys: girls 1.6:1). 57.5% adolescents reported recurrent
      headaches in past one year. Migraine was the most prevalent (17.2%) headache
      followed by unspecified (14.9%) and tension type headache (11%). Family history
      of headache was more common in adolescents with headache (p < 0.001) compared to
      those without headache. Average age of headache onset was 11.33 yr (10.72 yr in
      girls vs. 11.75 years in boys; p < 0.001). 37.1% adolescents complained of
      progression of headache since its onset. A significantly higher proportion of
      girls suffered headache (p=0.018), particularly migraine, than boys. However,
      other characteristics of headache were not dependent upon gender. Headache was
      more prevalent in higher grades. CONCLUSION: Primary Recurrent headaches are
      prevalent in Indian adolescents and migraine is comparatively the most prevalent
      type of headache. Female gender and increasing age is associated with higher
      chances to have headache, particularly migraine. It progresses in approximately
      one third of sufferers and aura increases the chances of worsening of headache.

PMID- 19381510
TI  - Bronchopulmonary dysplasia in very low birth weight infants.
AB  - OBJECTIVE: The developments in newborn care have enabled many more very low birth
      weight premature infants to live. The aim of our study was to determine the risk
      factors for bronchopulmonary dysplasia (BPD) development by evaluating mild and
      moderate/severe BPD in extramural neonates with a birth weight <1501 g. METHODS:
      A case-control study was conducted between January 1, 2004- December 31, 2006 at
      the Dr. Sami Ulus Children's Hospital Neonatal Intensive Care Unit. Patients with
      BPD and without BPD were compared. Bronchopulmonary dysplasia was diagnosed and
      classified according to the Bancalari criteria. One-hundred and six (106)
      extramural premature infants with a birth weight <1501 g and admitted to the
      Neonatal Unit in the first three days of life and survived for more than 28
      postnatal days were included. Patients with multiple congenital anomalies and
      complex cardiac pathologies were excluded. The maternal and neonatal risk
      factors, clinical features, mechanical ventilation treatment were compared. The
      principal risk factors for BPD development were analyzed and followed by logistic
      regression test. RESULTS: The diagnosis was mild BPD in 27 of the 106 patients
      and moderate/severe BPD in 29. The incidence of BPD was 52.8%. Fifty of 106
      patients had no BPD. Analysis of risk factors revealed that gestational age < or
      =28 weeks (p=0.019), birth weight < or =1000 g (p=0.007), hypothermia (p=0.003),
      acidosis (p=0.003) and hypotension (p=0.005) at admission, respiratory distress
      syndrome (RDS) ( p<0.001), mechanical ventilation therapy (p<0.001), surfactant
      therapy (p=0.005), higher amount of mean fluid therapy on 7(th) days (p=0.008),
      nosocomial infection (p<0.001), higher amount of mean packed red cell
      transfusions (p<0.001) and more than two packed red cell transfusions (p=0.033)
      were risk factors associated with the development of BPD. Multivariant logistic
      regression analysis showed acidosis at admission (OR 5.12, 95%CI 1.17-22.27,
      p=0.029), surfactant treatment (OR 7.53, 95%CI 2.14-26.45, p=0.002), nosocomial
      infections (OR 4.66, 95%CI 1.27-17.12, p=0.02) and PDA (OR 9.60, 95%CI 2.23
      41.22, p=0.002) were risk factors increasing the severity of BPD. CONCLUSION: The
      most important risk factors for BPD development in our study were RDS and
      nosocomial infections while the presence of acidosis at admission, surfactant
      administration, nosocomial infections and the presence of PDA were the most
      important risk factors regarding BPD severity. Presence of acidosis at admission
      as a risk factor emphasized the importance of suitable transport conditions for
      premature infants.

PMID- 19381511
TI  - Serum and hair zinc in severely malnourished Bangladeshi children associated with
      or without acute lower respiratory infection.
AB  - OBJECTIVE: To assess the zinc status in Bangladeshi children suffering from
      severe protein energy malnutrition (severe PEM), acute lower respiratory
      infection (ALRI), PEM presented with ALRI and to evaluate the relationship of
      zinc status with aforementioned clinical conditions. METHODS: We assessed zinc
      status by simultaneous estimation of serum and hair zinc of Bangladeshi children
      less than 5 yr of age suffering from severe PEM, ALRI, severe PEM presented with
      ALRI and compared them with zinc status of well-nourished healthy children
      (control) in a hospital based cross sectional four cell study. Zinc concentration
      was estimated by Flame atomic absorption spectrophotometry. RESULTS: Total one
      hundred and fifty two children were enrolled and number of children enrolled in
      severe PEM, ALRI, ALRI with PEM and control were 47, 35, 32 and 38 respectively.
      Both serum and hair zinc in univariate analysis were found significantly (p<0.05)
      low in severe PEM, ALRI and severe PEM associated with ALRI. However, in
      multivariate analysis, when serum and hair zinc were included in the same model,
      both serum and hair zinc were found to have significant negative association with
      PEM (p=0.002 & 0.013 respectively) and with ALRI only when ALRI was associated
      with PEM (p=0.043 and 0.034 respectively). CONCLUSION: Severe PEM and PEM with
      ALRI were significantly associated with low zinc status.

PMID- 19381512
TI  - Persistent thrombocytopenia following dengue shock syndrome.

PMID- 19381513
TI  - Typhoid fever and viral hepatitis.

PMID- 19381514
TI  - Awareness and health care seeking for newborn danger signs among mothers in peri
      urban Wardha.
AB  - OBJECTIVE: To find out awareness of mothers about newborn danger signs and their
      health care seeking behavior for sick newborns in the peri urban field practice
      area of Urban Health Centre in Wardha. METHODS: Triangulated study of
      quantitative (survey) and qualitative (mapping, pair-wise ranking exercise)
      methods were undertaken. 72 identified mothers of children (0-11 months) in
      social mapping exercise were interviewed by trained social workers using pre
      designed and pre-tested questionnaire and by paying house to house visits. The
      structured questionnaire covered information on newborn danger signs, health care
      seeking and socio-demographic information. The data was analyzed by using
      Epi_info software package. A pair-wise ranking exercise for assessment of
      preferred health care facility for sick newborn was undertaken with the group of
      purposively selected mothers. RESULTS: Out of 72 mothers, 29 (40.3%), 16 (22.2%)
      and 10 (13.9%) identified difficulty in breathing, poor sucking and
      lethargy/unconsciousness as newborn danger signs respectively. Only 7(9.7%) and 2
      (2.8%) identified convulsion and hypothermia as newborn danger signs
      respectively. About 27 (37.5%) babies were sick during newborn period. About
      11(15.3%) and 8 (11.1%) were reported to have poor sucking and difficulty in
      breathing respectively. All sick newborns with danger signs were taken to the
      doctor and only two mothers consulted faith healer for treatment. CONCLUSION:
      Considering the poor awareness of mothers regarding newborn danger signs, there
      is need for raising awareness building which required for early recognition and
      prompt treatment. Apart from strengthening government health facilities, the
      capacity of intermediate non government health care providers should be developed
      for newborn care.

PMID- 19381515
TI  - Spectrum of hemoglobinopathies in Eastern Uttar Pradesh.

PMID- 19381516
TI  - Antithymocyte globulin and cyclosporin in children with acquired aplastic anemia.

PMID- 19381517
TI  - Gut prolapse into the perineum in a case of sexual assault.
AB  - A six-year-old female victim of sexual assault, with grade IV perineal injury
      with massive intestinal prolapse out of the perineum, is reported to highlight
      the severity of injury during sexual assaults.

PMID- 19381518
TI  - BFHI in a tertiary care hospital: does being Baby friendly affect lactation
      success?
AB  - To study the impact of Baby friendly policies on lactation success, a semi
      structured questionnaire was administered to mothers of babies attending the well
      baby clinic of an urban tertiary care Baby Friendly Hospital. The feeding
      practices of outborn babies was compared to inborn babies (Baby friendly
      hospital). No major differences were found in the duration and success of
      lactation among the 2 groups. More intensive efforts and public awareness is
      required if the ideals of a baby friendly hospital are to be met.

PMID- 19381519
TI  - Prevalence of goitre among school children in Belgaum district.
AB  - OBJECTIVE: A school survey was conducted to estimate the prevalence of goitre
      among schoolchildren in Belgaum district. METHODS: A cross-sectional study was
      conducted in primary, middle and high schools of villages selected. All the
      children of the selected schools were examined for the presence of goitre and the
      salt samples obtained from their homes were tested for iodine content. RESULTS:
      Overall prevalence of goitre was 16.7%. Prevalence of palpable goitre was 16.4 %
      and visible goitre was very low (0.3%). Higher prevalence was found among females
      (21.1%) when compared to that of male children (12.8 %). Prevalence of goitre
      increased significantly with advancement of age until 16-yr. 72.1 % children were
      consuming rock salt and only 27.9 % were consuming powdered salt at their homes.
      Estimation of Iodine content in the salt samples showed that 68.7 % of the sample
      had inadequate iodine content. Prevalence of goitre was significantly high among
      children who consumed rock salt (16.2%) as compared to those who used powdered
      salt (11%) CONCLUSION: Strict implementation of salt codization and marketing in
      rural area is desired. Also health education programme be showed.

PMID- 19381520
TI  - Diagnosis of renal stones with underlying metabolic abnormalities using FTIR
      spectroscopy.

PMID- 19381521
TI  - Ultrasound microbubble contrast agents: application to therapy for peripheral
      vascular disease.
AB  - Ultrasound contrast agents are not only effective in ultrasonic imaging but are
      also important tools for drug or gene delivery. Ultrasound beams can disrupt
      microbubbles and cell membranes, offering the opportunity to locally deliver
      drugs or genes. Liposome-shelled microbubbles have many advantages and are widely
      used in many applications, while Lipofectamine (Invitrogen, Life Technologies,
      Carlsbad, CA, USA), as a material of microbubble membranes, has been used to
      enhance the effects of gene delivery. Ultrasound contrast agents that have
      therapeutic effects can be used for treating peripheral vascular diseases,
      particularly in thrombotic and angiogenic diseases. A combination of targeted
      contrast agent and drug-carrying contrast agent may be safer and more effective
      in treating thrombosis. Vascular endothelial growth factor-loaded microbubbles
      are expected to treat a variety of neovascular diseases such as severe limb
      ischemia and other diseases. Although there are several limitations in the
      application of therapeutic ultrasound microbubble contrast agents, it will offer
      a new hope for the treatment of peripheral vascular disease.

PMID- 19381522
TI  - Comparison of inhaled and intravenous milrinone in patients with pulmonary
      hypertension undergoing mitral valve surgery.
AB  - INTRODUCTION: Increased pulmonary vascular resistance (PVR) is detrimental to
      cardiac output in postoperative cardiac-surgery patients. The aim of this study
      was to investigate the postoperative hemodynamic effects of milrinone inhalation,
      and determine whether it has a selective effect of pulmonary vasodilation in
      patients with pulmonary hypertension undergoing mitral valve replacement surgery.
      METHODS: In this study, 48 patients with pulmonary hypertension who underwent
      mitral valve replacement surgery were included. Patients were randomly divided
      into two groups with 24 patients in each: the inhaled group and the control group
      (intravenous [i.v.] milrinone). In the inhaled group, milrinone was administered
      with a jet nebulizer, and nebulized for 4 hours. In the control group, patients
      received a bolus of 50 microg/kg i.v. milrinone, then received a continuous
      milrinone infusion, 0.5 microg/kg/min, for 4 hours. A number of hemodynamic
      changes in all patients were evaluated. RESULTS: With milrinone administration,
      mean pulmonary artery pressure (MPAP) and PVR showed a comparable decrease in
      both groups. However, after initiation of milrinone, both mean arterial pressure
      and systemic vascular resistance in the inhaled group were significantly higher
      than in the control group. MPAP and PVR returned to baseline values 60 minutes
      after termination of milrinone inhalation. In addition, in the inhaled group,
      there was a reduction in intrapulmonary shunt fraction (Qs/Qt), with an
      improvement in PaO(2)/FiO(2) (arterial oxygen tension/fraction of inspired
      oxygen). CONCLUSION: The major advantage of inhaled milrinone is its pulmonary
      selectivity, thereby avoiding systemic side effects and ventilation-perfusion
      mismatch. Inhaled milrinone is an effective pulmonary vasodilator and appears to
      be an alternative promising approach in addressing the problem of right
      ventricular decompensation following cardiopulmonary bypass.

PMID- 19381523
TI  - Rate of bacterial eradication by ophthalmic solutions of fourth-generation
      fluoroquinolones.
AB  - INTRODUCTION: Antibacterial activity of ophthalmic fourth-generation
      fluoroquinolones has traditionally been evaluated by comparing only their active
      ingredients, gatifloxacin and moxifloxacin. However, ophthalmic formulations of
      fourth-generation fluoroquinolones differ in terms of the inclusion of
      preservatives. While gatifloxacin ophthalmic solution 0.3% (Zymar; Allergan,
      Inc., Irvine, CA, USA) contains 0.005% benzalkonium chloride (BAK), moxifloxacin
      ophthalmic solution 0.5% (Vigamox; Alcon Laboratories, Inc., Fort Worth, TX, USA)
      is preservative-free. Recent studies have demonstrated that the presence of BAK
      dramatically affects the antibacterial activity of the ophthalmic formulation of
      gatifloxacin. This study was designed to compare the kill rates of ophthalmic
      solutions of fourth-generation fluoroquinolones against isolates of common ocular
      bacterial pathogens. METHODS: Approximately 5.6 log(10) colony-forming units
      (CFU)/mL of Haemophilus influenzae (n=1), Streptococcus pneumoniae (n=1),
      Staphylococcus aureus (n=2), methicillin-resistant Staphylococcus aureus (MRSA)
      (n=4), methicillinresistant Staphylococcus epidermidis (MRSE) (n=4), and
      fluoroquinolone-resistant S. epidermidis (n=1) were incubated with ophthalmic
      solutions of either gatifloxacin or moxifloxacin. Viable bacteria were quantified
      at specific time points up to 60 minutes. RESULTS: Gatifloxacin 0.3% completely
      eradicated H. influenzae and Strep. pneumoniae in 5 minutes, one of two S. aureus
      isolates in 15 minutes, and the other S. aureus isolate in 60 minutes.
      Gatifloxacin 0.3% completely killed all MRSA, MRSE, and fluoroquinolone-resistant
      S. epidermidis isolates in 15 minutes. Moxifloxacin 0.5% completely eradicated
      Strep. pneumoniae and one of four MRSA isolates in 60 minutes. All other isolates
      incubated with moxifloxacin 0.5% retained viable bacteria ranging from 1.8 to 4.4
      log(10) CFU/mL. CONCLUSIONS: The ophthalmic solution of gatifloxacin 0.3%
      eradicated bacteria that frequently cause postoperative ocular infections
      substantially faster than did the ophthalmic solution of moxifloxacin 0.5%.

PMID- 19381524
TI  - Learning global models of transcriptional regulatory networks from data.
AB  - Organisms must continually adapt to changing cellular and environmental factors
      (e.g., oxygen levels) by altering their gene expression patterns. At the same
      time, all organisms must have stable gene expression patterns that are robust to
      small fluctuations in environmental factors and genetic variation. Learning and
      characterizing the structure and dynamics of Regulatory Networks (RNs), on a
      whole-genome scale, is a key problem in systems biology. Here, we review the
      challenges associated with inferring RNs in a solely data-driven manner,
      concisely discuss the implications and contingencies of possible procedures that
      can be used, specifically focusing on one such procedure, the Inferelator.
      Importantly, the Inferelator explicitly models the temporal component of
      regulation, can learn the interactions between transcription factors and
      environmental factors, and attaches a statistically meaningful weight to every
      edge. The result of the Inferelator is a dynamical model of the RN that can be
      used to model the time-evolution of cell state.

PMID- 19381525
TI  - Methods to reconstruct and compare transcriptional regulatory networks.
AB  - The availability of completely sequenced genomes and the wealth of literature on
      gene regulation have enabled researchers to model the transcriptional regulation
      system of some organisms in the form of a network. In order to reconstruct such
      networks in non-model organisms, three principal approaches have been taken.
      First, one can transfer the interactions between homologous components from a
      model organism to the organism of interest. Second, microarray experiments can be
      used to detect patterns in gene expression that stem from regulatory
      interactions. Finally, knowledge of experimentally characterized transcription
      factor binding sites can be used to analyze the promoter sequences in a genome in
      order to identify potential binding sites. In this chapter, we will focus in
      detail on the first approach and describe methods to reconstruct and analyze the
      transcriptional regulatory networks of uncharacterized organisms by using a known
      regulatory network as a template.

PMID- 19381526
TI  - Detecting hierarchical modularity in biological networks.
AB  - Spatially or chemically isolated modules that carry out discrete functions are
      considered fundamental building blocks of cellular organization. However,
      detecting them in highly integrated biological networks requires a thorough
      understanding of the organization of these networks. In this chapter I argue that
      many biological networks are organized into many small, highly connected
      topologic modules that combine in a hierarchical manner into larger, less
      cohesive units. On top of a scale-free degree distribution, these networks show a
      power law scaling of the clustering coefficient with the node degree, a property
      that can be used as a signature of hierarchical organization. As a case study, I
      identify the hierarchical modules within the Escherichia coli metabolic network,
      and show that the uncovered hierarchical modularity closely overlaps with known
      metabolic functions.

PMID- 19381527
TI  - Prediction and integration of regulatory and protein-protein interactions.
AB  - Knowledge of transcriptional regulatory interactions (TRIs) is essential for
      exploring functional genomics and systems biology in any organism. While several
      results from genome-wide analysis of transcriptional regulatory networks are
      available, they are limited to model organisms such as yeast ( 1 ) and worm ( 2
      ). Beyond these networks, experiments on TRIs study only individual genes and
      proteins of specific interest. In this chapter, we present a method for the
      integration of various data sets to predict TRIs for 54 organisms in the Bioverse
      ( 3 ). We describe how to compile and handle various formats and identifiers of
      data sets from different sources and how to predict TRIs using a homology-based
      approach, utilizing the compiled data sets. Integrated data sets include
      experimentally verified TRIs, binding sites of transcription factors, promoter
      sequences, protein subcellular localization, and protein families. Predicted TRIs
      expand the networks of gene regulation for a large number of organisms. The
      integration of experimentally verified and predicted TRIs with other known
      protein-protein interactions (PPIs) gives insight into specific pathways, network
      motifs, and the topological dynamics of an integrated network with gene
      expression under different conditions, essential for exploring functional
      genomics and systems biology.

PMID- 19381528
TI  - Computational reconstruction of protein-protein interaction networks: algorithms
      and issues.
AB  - Accurate mapping of protein-protein interaction networks in model organisms is a
      crucial first step toward subsequent quantitative study of the organization and
      evolution of biological systems. Data quality of experimental interactome maps
      can be assessed and improved by integrating multiple sources of evidence using
      machine learning methods. Here we describe the commonly used algorithms for
      predicting protein-protein interaction by genome data integration, and discuss
      several important yet often overlooked issues in computational reconstruction of
      protein-protein interaction networks.

PMID- 19381529
TI  - Prediction of protein-protein interactions: a study of the co-evolution model.
AB  - The concept of molecular co-evolution drew attention in recent years as the basis
      for several algorithms for the prediction of protein-protein interactions. While
      being successful on specific data, the concept has never been tested on a large
      set of proteins. In this chapter we analyze the feasibility of the co-evolution
      principle for protein-protein interaction prediction through one of its
      derivatives, the correlated divergence model. Given two proteins, the model
      compares the patterns of divergence of their families and assigns a score based
      on the correlation between the two. The working hypothesis of the model
      postulates that the stronger the correlation the more likely is that the two
      proteins interact. Several novel variants of this model are considered, including
      algorithms that attempt to identify the subset of the database proteins (the
      homologs of the query proteins) that are more likely to interact. We test the
      models over a large set of protein interactions extracted from several sources,
      including BIND, DIP, and HPRD.

PMID- 19381530
TI  - Inferring protein-protein interactions from multiple protein domain combinations.
AB  - The ever accumulating wealth of knowledge about protein interactions and the
      domain architecture of involved proteins in different organisms offers ways to
      understand the intricate interplay between interactome and proteome. Ultimately,
      the combination of these sources of information will allow the prediction of
      interactions among proteins where only domain composition is known. Based on the
      currently available protein-protein interaction and domain data of Saccharomyces
      cerevisiae and Drosophila melanogaster we introduce a novel method, Maximum
      Specificity Set Cover (MSSC), to predict potential protein-protein interactions.
      Utilizing interactions and domain architectures of domains as training sets, this
      algorithm employs a set cover approach to partition domain pairs, which allows
      the explanation of the underlying protein interaction to the largest degree of
      specificity. While MSSC in its basic version only considers domain pairs as the
      driving force between interactions, we also modified the algorithm to account for
      combinations of more than two domains that govern a protein-protein interaction.
      This approach allows us to predict the previously unknown protein-protein
      interactions in S. cerevisiae and D. melanogaster, with a degree of sensitivity
      and specificity that clearly outscores other approaches. As a proof of concept we
      also observe high levels of co-expression and decreasing GO distances between
      interacting proteins. Although our results are very encouraging, we observe that
      the quality of predictions significantly depends on the quality of interactions,
      which were utilized as the training set of the algorithm. The algorithm is part
      of a Web portal available at http://ppi.cse.nd.edu .

PMID- 19381531
TI  - Biological Network Inference and analysis using SEBINI and CABIN.
AB  - Attaining a detailed understanding of the various biological networks in an
      organism lies at the core of the emerging discipline of systems biology. A
      precise description of the relationships formed between genes, mRNA molecules,
      and proteins is a necessary step toward a complete description of the dynamic
      behavior of an organism at the cellular level, and toward intelligent, efficient,
      and directed modification of an organism. The importance of understanding such
      regulatory, signaling, and interaction networks has fueled the development of
      numerous in silico inference algorithms, as well as new experimental techniques
      and a growing collection of public databases. The Software Environment for
      BIological Network Inference (SEBINI) has been created to provide an interactive
      environment for the deployment, evaluation, and improvement of algorithms used to
      reconstruct the structure of biological regulatory and interaction networks.
      SEBINI can be used to analyze high-throughput gene expression, protein abundance,
      or protein activation data via a suite of state-of-the-art network inference
      algorithms. It also allows algorithm developers to compare and train network
      inference methods on artificial networks and simulated gene expression
      perturbation data. SEBINI can therefore be used by software developers wishing to
      evaluate, refine, or combine inference techniques, as well as by
      bioinformaticians analyzing experimental data. Networks inferred from the SEBINI
      software platform can be further analyzed using the Collective Analysis of
      Biological Interaction Networks (CABIN) tool, which is an exploratory data
      analysis software that enables integration and analysis of protein-protein
      interaction and gene-to-gene regulatory evidence obtained from multiple sources.
      The collection of edges in a public database, along with the confidence held in
      each edge (if available), can be fed into CABIN as one "evidence network," using
      the Cytoscape SIF file format. Using CABIN, one may increase the confidence in
      individual edges in a network inferred by an algorithm in SEBINI, as well as
      extend such a network by combining it with species-specific or generic
      information, e.g., known protein-protein interactions or target genes identified
      for known transcription factors. Thus, the combined SEBINI-CABIN toolkit aids in
      the more accurate reconstruction of biological networks, with less effort, in
      less time.A demonstration web site for SEBINI can be accessed from
      https://www.emsl.pnl.gov/SEBINI/RootServlet . Source code and PostgreSQL database
      schema are available under open source license. CONTACT: ronald.taylor@pnl.gov.
      For commercial use, some algorithms included in SEBINI require licensing from the
      original developers. CABIN can be downloaded from
      http://www.sysbio.org/dataresources/cabin.stm . CONTACT: mudita.singhal@pnl.gov.

PMID- 19381532
TI  - Computational representation of biological systems.
AB  - Integration of large and diverse biological data sets is a daunting problem
      facing systems biology researchers. Exploring the complex issues of data
      validation, integration, and representation, we present a systematic approach for
      the management and analysis of large biological data sets based on data
      warehouses. Our system has been implemented in the Bioverse, a framework
      combining diverse protein information from a variety of knowledge areas such as
      molecular interactions, pathway localization, protein structure, and protein
      function.

PMID- 19381533
TI  - The Bioverse API and web application.
AB  - The Bioverse is a framework for creating, warehousing and presenting biological
      information based on hierarchical levels of organisation. The framework is guided
      by a deeper philosophy of desiring to represent all relationships between all
      components of biological systems towards the goal of a wholistic picture of
      organismal biology. Data from various sources are combined into a single
      repository and a uniform interface is exposed to access it. The power of the
      approach of the Bioverse is that, due to its inclusive nature, patterns emerge
      from the acquired data and new predictions are made. The implementation of this
      repository (beginning with acquisition of source data, processing in a pipeline,
      and concluding with storage in a relational database) and interfaces to the data
      contained in it, from a programmatic application interface to a user friendly web
      application, are discussed.

PMID- 19381534
TI  - Comparing algorithms for clustering of expression data: how to assess gene
      clusters.
AB  - Clustering is a popular technique commonly used to search for groups of similarly
      expressed genes using mRNA expression data. There are many different clustering
      algorithms and the application of each one will usually produce different
      results. Without additional evaluation, it is difficult to determine which
      solutions are better.In this chapter we discuss methods to assess algorithms for
      clustering of gene expression data. In particular, we present a new method that
      uses two elements: an internal index of validity based on the MDL principle and
      an external index of validity that measures the consistency with experimental
      data. Each one is used to suggest an effective set of models, but it is only the
      combination of both that is capable of pinpointing the best model overall. Our
      method can be used to compare different clustering algorithms and pick the one
      that maximizes the correlation with functional links in gene networks while
      minimizing the error rate. We test our methods on several popular clustering
      algorithms as well as on clustering algorithms that are specially tailored to
      deal with noisy data. Finally, we propose methods for assessing the significance
      of individual clusters and study the correspondence between gene clusters and
      biochemical pathways.

PMID- 19381535
TI  - Effects of functional bias on supervised learning of a gene network model.
AB  - Gene networks have proven to be an effective approach for modeling cellular
      systems, capable of capturing some of the extreme complexity of cells in a formal
      theoretical framework. Not surprisingly, this complexity, combined with our still
      limited amount of experimental data measuring the genes and their interactions,
      makes the reconstruction of gene networks difficult. One powerful strategy has
      been to analyze functional genomics data using supervised learning of network
      relationships based upon reference examples from our current knowledge. However,
      this reliance on the set of reference examples for the supervised learning can
      introduce major pitfalls, with misleading reference sets resulting in suboptimal
      learning. There are three requirements for an effective reference set:
      comprehensiveness, reliability, and freedom from bias. Perhaps not too
      surprisingly, our current knowledge about gene function is highly biased toward
      several specific biological functions, such as protein synthesis. This functional
      bias in the reference set, especially combined with the corresponding functional
      bias in data sets, induces biased learning that can, in turn, lead to false
      positive biological discoveries, as we show here for the yeast Saccharomyces
      cerevisiae. This suggests that careful use of current knowledge and genomics data
      is required for successful gene network modeling using the supervised learning
      approach. We provide guidance for better use of these data in learning gene
      networks.

PMID- 19381536
TI  - Structure-based ab initio prediction of transcription factor-binding sites.
AB  - We present an all-atom molecular modeling method that can predict the binding
      specificity of a transcription factor based on its 3D structure, with no further
      information required. We use molecular dynamics and free energy calculations to
      compute the relative binding free energies for a transcription factor with
      multiple possible DNA sequences. These sequences are then used to construct a
      position weight matrix to represent the transcription factor-binding sites. Free
      energy differences are calculated by morphing one base pair into another using a
      multi-copy representation in which multiple base pairs are superimposed at a
      single DNA position. Water-mediated hydrogen bonds between transcription factor
      side chains and DNA bases are known to contribute to binding specificity for
      certain transcription factors. To account for this important effect, the
      simulation protocol includes an explicit molecular water solvent and counter
      ions. For computational efficiency, we use a standard additive approximation for
      the contribution of each DNA base pair to the total binding free energy. The
      additive approximation is not strictly necessary, and more detailed computations
      could be used to investigate non-additive effects.

PMID- 19381537
TI  - Connecting protein interaction data, mutations, and disease using bioinformatics.
AB  - Understanding how mutations lead to changes in protein function and/or protein
      interaction is critical to understanding the molecular causes of clinical
      phenotypes. In this method, we present a path toward integration of protein
      interaction data and mutation data and then demonstrate the identification of a
      subset of proteins and interactions that are important to a particular disease.
      We then build a statistical model of disease mutations in this disease-associated
      subset of proteins, and visualize these results. Using Alzheimer's disease (AD)
      as case implementation, we find that we are able to identify a subset of proteins
      involved in AD and discriminate disease-associated mutations from SNPs in these
      proteins with 83% accuracy. As the molecular causes of disease become more
      understood, models such as these will be useful for identifying candidate
      variants most likely to be causative.

PMID- 19381538
TI  - Using evolutionary information to find specificity-determining and co-evolving
      residues.
AB  - Intricate networks of protein interactions rely on the ability of a protein to
      recognize its targets: other proteins, ligands, and sites on DNA and RNA. To
      recognize other molecules, it was suggested that a protein uses a small set of
      specificity-determining residues (SDRs). How can one find these residues in
      proteins and distinguish them from other functionally important amino acids? A
      number of bioinformatics methods to predict SDRs have been developed in recent
      years. These methods use genomic information and multiple sequence alignments to
      identify positions exhibiting a specific pattern of conservation and variability.
      The challenge is to delineate the evolutionary pattern of SDRs from that of the
      active site residues and the residues responsible for formation of the protein's
      structure. The phylogenetic history of a protein family makes such analysis
      particularly hard. Here we present two methods for finding the SDRs and the co
      evolving residues (CERs) in proteins. We use a Monte Carlo approach for
      statistical inference, allowing us to reveal specific evolutionary patterns of
      SDRs and CERs. We apply these methods to study specific recognition in the
      bacterial two-component system and in the class Ia aminoacyl-tRNA synthetases.
      Our results agree well with structural information and the experimental analyses
      of these systems. Our results point at the complex and distinct patterns
      characteristic of the evolution of specificity in these systems.

PMID- 19381539
TI  - Enzyme function prediction with interpretable models.
AB  - Enzymes play central roles in metabolic pathways, and the prediction of metabolic
      pathways in newly sequenced genomes usually starts with the assignment of genes
      to enzymatic reactions. However, genes with similar catalytic activity are not
      necessarily similar in sequence, and therefore the traditional sequence
      similarity-based approach often fails to identify the relevant enzymes, thus
      hindering efforts to map the metabolome of an organism.Here we study the direct
      relationship between basic protein properties and their function. Our goal is to
      develop a new tool for functional prediction (e.g., prediction of Enzyme
      Commission number), which can be used to complement and support other techniques
      based on sequence or structure information. In order to define this mapping we
      collected a set of 453 features and properties that characterize proteins and are
      believed to be related to structural and functional aspects of proteins. We
      introduce a mixture model of stochastic decision trees to learn the set of
      potentially complex relationships between features and function. To study these
      correlations, trees are created and tested on the Pfam classification of
      proteins, which is based on sequence, and the EC classification, which is based
      on enzymatic function. The model is very effective in learning highly diverged
      protein families or families that are not defined on the basis of sequence. The
      resulting tree structures highlight the properties that are strongly correlated
      with structural and functional aspects of protein families, and can be used to
      suggest a concise definition of a protein family.

PMID- 19381540
TI  - A maximum likelihood method for reconstruction of the evolution of eukaryotic
      gene structure.
AB  - Spliceosomal introns are one of the principal distinctive features of eukaryotes.
      Nevertheless, different large-scale studies disagree about even the most basic
      features of their evolution. In order to come up with a more reliable
      reconstruction of intron evolution, we developed a model that is far more
      comprehensive than previous ones. This model is rich in parameters, and
      estimating them accurately is infeasible by straightforward likelihood
      maximization. Thus, we have developed an expectation-maximization algorithm that
      allows for efficient maximization. Here, we outline the model and describe the
      expectation-maximization algorithm in detail. Since the method works with intron
      presence-absence maps, it is expected to be instrumental for the analysis of the
      evolution of other binary characters as well.

PMID- 19381541
TI  - Guidance for data collection and computational modelling of regulatory networks.
AB  - Many model regulatory networks are approaching the depth of characterisation of
      bacteriophage lambda, wherein the vast majority of individual components and
      interactions are identified, and research can focus on understanding whole
      network function and the role of interactions within that broader context. In
      recent years, the study of the system-wide behaviour of phage lambda's genetic
      regulatory network has been greatly assisted by the combination of quantitative
      measurements with theoretical and computational analyses. Such research has
      demonstrated the value of a number of general principles and guidelines for
      making use of the interplay between experiments and modelling. In this chapter we
      discuss these guidelines and provide illustration through reference to case
      studies from phage lambda biology.In our experience, computational modelling is
      best facilitated with a large and diverse set of quantitative, in vivo data,
      preferably obtained from standardised measurements and expressed as absolute
      units rather than relative units. Isolation of subsets of regulatory networks may
      render a system amenable to 'bottom-up' modelling, providing a valuable tool to
      the experimental molecular biologist. Decoupling key components and rendering
      their concentration or activity an independent experimental variable provide
      excellent information for model building, though conclusions drawn from isolated
      and/or decoupled systems should be checked against studies in the full
      physiological context; discrepancies are informative. The construction of a model
      makes possible in silico experiments, which are valuable tools for both the data
      analysis and the design of wet experiments.

PMID- 19381542
TI  - Kinetic modeling of biological systems.
AB  - The dynamics of how the constituent components of a natural system interact
      defines the spatio-temporal response of the system to stimuli. Modeling the
      kinetics of the processes that represent a biophysical system has long been
      pursued with the aim of improving our understanding of the studied system. Due to
      the unique properties of biological systems, in addition to the usual
      difficulties faced in modeling the dynamics of physical or chemical systems,
      biological simulations encounter difficulties that result from intrinsic multi
      scale and stochastic nature of the biological processes.This chapter discusses
      the implications for simulation of models involving interacting species with very
      low copy numbers, which often occur in biological systems and give rise to
      significant relative fluctuations. The conditions necessitating the use of
      stochastic kinetic simulation methods and the mathematical foundations of the
      stochastic simulation algorithms are presented. How the well-organized structural
      hierarchies often seen in biological systems can lead to multi-scale problems and
      the possible ways to address the encountered computational difficulties are
      discussed. We present the details of the existing kinetic simulation methods and
      discuss their strengths and shortcomings. A list of the publicly available
      kinetic simulation tools and our reflections for future prospects are also
      provided.

PMID- 19381543
TI  - Network dynamics.
AB  - Probably one of the most characteristic features of a living system is its
      continual propensity to change as it juggles the demands of survival with the
      need to replicate. Internally these adjustments are manifest as changes in
      metabolite, protein, and gene activities. Such changes have become increasingly
      obvious to experimentalists, with the advent of high-throughput technologies. In
      this chapter we highlight some of the quantitative approaches used to rationalize
      the study of cellular dynamics. The chapter focuses attention on the analysis of
      quantitative models based on differential equations using biochemical control
      theory. Basic pathway motifs are discussed, including straight chain, branched,
      and cyclic systems. In addition, some of the properties conferred by positive and
      negative feedback loops are discussed, particularly in relation to bistability
      and oscillatory dynamics.

PMID- 19381544
TI  - Exploring pathways from gene co-expression to network dynamics.
AB  - One of the major challenges in post-genomic research is to understand how
      physiological and pathological phenotypes arise from the networks or connectivity
      of expressed genes. In addressing this issue, we have developed two computational
      algorithms, CoExMiner and PathwayPro, to explore static features of gene co
      expression and dynamic behaviors of gene networks. CoExMiner is based on B-spline
      approximation followed by the coefficient of determination (CoD) estimation for
      modeling gene co-expression patterns. The algorithm allows the exploration of
      transcriptional responses that involve coordinated expression of genes encoding
      proteins which work in concert in the cell. PathwayPro is based on a finite-state
      Markov chain model for mimicking dynamic behaviors of a transcriptional network.
      The algorithm allows quantitative assessment of a wide range of network
      responses, including susceptibility to disease, potential usefulness of a given
      drug, and consequences of such external stimuli as pharmacological interventions
      or caloric restriction. We demonstrated the applications of CoExMiner and
      PathwayPro by examining gene expression profiles of ligands and receptors in
      cancerous and non-cancerous cells and network dynamics of the leukemia-associated
      BCR-ABL pathway. The examinations disclosed both linear and nonlinear
      relationships of ligand-receptor interactions associated with cancer development,
      identified disease and drug targets of leukemia, and provided new insights into
      biology of the diseases. The analysis using these newly developed algorithms show
      the great usefulness of computational systems biology approaches for biological
      and medical research.

PMID- 19381545
TI  - Methods for the inference of biological pathways and networks.
AB  - In this chapter, we discuss a number of approaches to network inference from
      large-scale functional genomics data. Our goal is to describe current methods
      that can be used to infer predictive networks. At present, one of the most
      effective methods to produce networks with predictive value is the Bayesian
      network approach. This approach was initially instantiated by Friedman et al. and
      further refined by Eric Schadt and his research group. The Bayesian network
      approach has the virtue of identifying predictive relationships between genes
      from a combination of expression and eQTL data. However, the approach does not
      provide a mechanistic bases for predictive relationships and is ultimately
      hampered by an inability to model feedback. A challenge for the future is to
      produce networks that are both predictive and provide mechanistic understanding.
      To do so, the methods described in several chapters of this book will need to be
      integrated. Other chapters of this book describe a number of methods to identify
      or predict network components such as physical interactions. At the end of this
      chapter, we speculate that some of the approaches from other chapters could be
      integrated and used to "annotate" the edges of the Bayesian networks. This would
      take the Bayesian networks one step closer to providing mechanistic
      "explanations" for the relationships between the network nodes.

PMID- 19381546
TI  - Inferring molecular interactions pathways from eQTL data.
AB  - Analysis of expression quantitative trait loci (eQTL) helps elucidate the
      connection between genotype, gene expression levels, and phenotype. However,
      standard statistical genetics can only attribute the changes in expression levels
      to loci on the genome, not specific genes. Each locus can contain many genes,
      making it very difficult to discover which gene is controlling the expression
      levels of other genes. Furthermore, it is even more difficult to find a pathway
      of molecular interactions responsible for controlling the expression levels. Here
      we describe a series of techniques for finding explanatory pathways by exploring
      the graphs of molecular interactions. We show several simple methods can find
      complete pathways that explain the mechanism of differential expression in eQTL
      data.

PMID- 19381547
TI  - Identification of cis-regulatory elements in gene co-expression networks using A
      GLAM.
AB  - Reliable identification and assignment of cis-regulatory elements in promoter
      regions is a challenging problem in biology. The sophistication of
      transcriptional regulation in higher eukaryotes, particularly in metazoans, could
      be an important factor contributing to their organismal complexity. Here we
      present an integrated approach where networks of co-expressed genes are combined
      with gene ontology-derived functional networks to discover clusters of genes that
      share both similar expression patterns and functions. Regulatory elements are
      identified in the promoter regions of these gene clusters using a Gibbs sampling
      algorithm implemented in the A-GLAM software package. Using this approach, we
      analyze the cell-cycle co-expression network of the yeast Saccharomyces
      cerevisiae, showing that this approach correctly identifies cis-regulatory
      elements present in clusters of co-expressed genes.

PMID- 19381548
TI  - Predicting riboswitch regulation on a genomic scale.
AB  - Riboswitches are vital components of many genomes. Covariance model searches for
      the characteristic architectures of riboswitch aptamer domains can be used to
      predict new examples of these structured RNAs. Since riboswitches generally
      function as cis-regulatory elements, examining the genomic contexts of these hits
      is critical for evaluating their biological relevance. With these two sources of
      comparative support, it is possible to identify riboswitches accurately from
      sequence information alone. Annotating riboswitches on a genomic scale enables
      more precise functions to be assigned to the proteins that they regulate, better
      defines their conserved aptamer structures by identifying diverged variants, and
      provides insight into how the genetic regulation of fundamental metabolic
      processes varies among species.

PMID- 19381549
TI  - Enzymatic ligation strategies for the preparation of purine riboswitches with
      site-specific chemical modifications.
AB  - One of the most versatile riboswitch classes refers to purine nucleoside
      metabolism. In the cell, purine riboswitches of the respective mRNAs either act
      at the transcriptional or translational level and off- or on-regulate genes upon
      binding to their dedicated ligands. Biophysical studies on ligand-induced folding
      of these RNA domains in vitro contribute to understanding their regulation
      mechanisms in vivo. For such studies, in particular, for approaches using
      fluorescence spectroscopy, the preparation of large RNAs with site-specific
      chemical modifications is required. Here, we describe a strategy for the
      preparation of riboswitch aptamers and aptamers adjoined to their expression
      platforms by chemical synthesis and enzymatic ligation. The modular design
      enables fast access to a large number of purine riboswitch derivatives with the
      modification of interest at any strand position. We exemplarily provide a
      detailed protocol for the preparation of adenosine deaminase (add) A-riboswitch
      variants with 2-aminopurine (AP) modifications at the 40-nmol scale.

PMID- 19381550
TI  - Application of fluorescent measurements for characterization of riboswitch-ligand
      interactions.
AB  - Riboswitches are recently discovered messenger RNA motifs involved in gene
      regulation. They modulate gene expression at various levels, such as
      transcription, translation, splicing, and mRNA degradation. Because riboswitches
      exhibit relatively complex structures, they are able to form highly complex
      ligand-binding sites, which enable the specific recognition of target metabolites
      in a complex cellular environment. Practically in all studied cases, riboswitches
      use ligand-induced conformational changes to control gene expression. To monitor
      the structural reorganization of riboswitches, we use the local fluorescent
      reporter 2-aminopurine (2AP), which is a structural analog of adenine. The 2AP
      fluorescence is strongly quenched when the fluorophore is involved in stacking
      interactions with surrounding bases, and can, therefore, be used to monitor local
      structural rearrangements. Here, we show specific examples in which 2AP
      fluorescence can be used to monitor structural changes in the aptamer domain of
      the S-adenosyl methionine (SAM) riboswitch and where it can be used as a ligand
      for the guanine riboswitch.

PMID- 19381551
TI  - Transcriptional approaches to riboswitch studies.
AB  - Natural RNA sensors of small molecules (a.k.a. riboswitches) regulate numerous
      metabolic genes. In bacteria, these RNA elements control transcription
      termination and translation initiation by changing the folding pathway of nascent
      RNA upon direct binding of a metabolite. To identify and study riboswitches we
      used in vitro reconstituted solid-phase transcription elongation/termination
      system. This approach allows for direct monitoring of ligand binding and
      riboswitch functioning, establishing the working concentration of a ligand as a
      function of RNA polymerase speed, and also probing RNA structure of the
      riboswitch. Using this system we have been able to identify and characterize
      first several riboswitches including those involved in vitamin biosynthesis and
      sulfur metabolism. The system can be utilized to facilitate biochemical studies
      of riboswitches in general, i.e., to simplify analysis of riboswitches that are
      not necessarily involved in transcriptional control.

PMID- 19381552
TI  - Kinetics of riboswitch regulation studied by in vitro transcription.
AB  - Riboswitches encompass messenger ribonucleic acid transcripts that sense the
      concentration of small molecule metabolites through binding the target compound
      and then control the expression of metabolite-related genes in response to the
      metabolite concentration. While much of the riboswitch-related research has
      focused on the remarkable ability of different aptamer domains to adopt the
      intricate structures required to bind a spectrum of biological metabolites with
      high affinity and specificity, less attention has been paid to the mechanism of
      riboswitch action. Specifically, the genetic control element of the riboswitch,
      known as the expression platform, must function cotranscriptionally in the case
      of transcription termination-controlled riboswitches. By correlating the
      transcriptional kinetics of the entire switch and the kinetics and thermodynamics
      of metabolite binding of the aptamer domain, it was found that the FMN-binding
      riboswitch in the 5' UTR of the Bacillus subtilis ribGBAHT operon functions as a
      kinetically controlled genetic switch chiefly dependent upon transcriptional
      pausing and the concentration of the target metabolite. This study has emphasized
      the importance of studying the switch in its entirety and in the context of an
      actively transcribing RNA polymerase. Herein I will describe the study of the
      kinetics of riboswitch transcription and the proposed mechanism for the
      transcription termination-associated riboswitch control of riboflavin-related
      genes.

PMID- 19381553
TI  - Molecular basis of RNA-mediated gene regulation on the adenine riboswitch by
      single-molecule approaches.
AB  - The adenine-specific pbuE riboswitch undergoes metal ion-dependent folding that
      involves a long-range tertiary loop-loop interaction between two stem loops.
      Fluorescence resonance energy transfer (FRET) and single-molecule FRET studies
      demonstrate the ability of the loops to interact in the absence of the ligand.
      Although the riboswitch can fold in the absence of adenine, ligand binding
      stabilizes this folded conformation by increasing the folding and decreasing the
      unfolding rates of the riboswitch. The presence of the ligand also decreases the
      magnesium ion concentration required to promote the loop-loop interaction. Single
      molecule FRET studies demonstrate that individual aptamer molecules exhibit great
      heterogeneity in the rates of folding and unfolding, which is reduced in the
      presence of adenine. Moreover, single-molecule FRET proposes that riboswitch
      folding proceeds through a complex landscape that involves a discrete
      intermediate.

PMID- 19381554
TI  - Methods for analysis of ligand-induced RNA conformational changes.
AB  - Encoded within many RNA sequences is the requisite information for folding of
      intricate three-dimensional structures. Moreover, many noncoding RNAs can adopt
      structurally distinct and functionally specialized conformations in response to
      specific cellular signals. These conformational transitions are often times
      accompanied by changes in hydrodynamic radii. Therefore, experimental methods
      that measure changes in hydrodynamic radius can be employed for study of signal
      induced RNA conformational changes. Several hydrodynamic methods, including
      analytical ultracentrifugation, size-exclusion chromatography, and nondenaturing
      gel electrophoresis, are briefly discussed herein.

PMID- 19381555
TI  - Monitoring RNA-ligand interactions using isothermal titration calorimetry.
AB  - Isothermal titration calorimetry (ITC) is a biophysical technique that measures
      the heat evolved or absorbed during a reaction to report the enthalpy, entropy,
      stoichiometry of binding, and equilibrium association constant. A significant
      advantage of ITC over other methods is that it can be readily applied to almost
      any RNA-ligand complex without having to label either molecule and can be
      performed under a broad range of pH, temperature, and ionic concentrations.
      During our application of ITC to investigate the thermodynamic details of the
      interaction of a variety of compounds with the purine riboswitch, we have
      explored and optimized experimental parameters that yield the most useful and
      reproducible results for RNAs. In this chapter, we detail this method using the
      titration of an adenine-binding RNA with 2,6-diaminopurine (DAP) as a practical
      example. Our insights should be generally applicable to observing the
      interactions of a broad range of molecules with structured RNAs.

PMID- 19381556
TI  - Preparation and crystallization of riboswitch-ligand complexes.
AB  - Riboswitches are mRNA regions that regulate the expression of genes in response
      to various cellular metabolites. These RNA sequences, typically situated in the
      untranslated regions of mRNAs, possess complex structures that dictate highly
      specific binding to certain ligands, such as nucleobases, coenzymes, amino acids,
      and sugars, without protein assistance. Depending on the presence of the ligand,
      metabolite-binding domains of riboswitches can adopt two alternative
      conformations, which define the conformations of the adjacent sequences involved
      in the regulation of gene expression. In order to understand in detail the nature
      of riboswitch-ligand interactions and the molecular basis of riboswitch-based
      gene expression control, it is necessary to determine the three-dimensional
      structures of riboswitch-ligand complexes. This chapter outlines the techniques
      that are employed to prepare riboswitch-ligand complexes for structure
      determination using X-ray crystallography. The chapter describes the principles
      of construct design, in vitro transcription, RNA purification, complex formation,
      and crystallization screening utilized during the successful crystallization of
      several riboswitches.

PMID- 19381557
TI  - Crystallization of the glmS ribozyme-riboswitch.
AB  - Procedures that were critical for crystallization of the glmS ribozyme-riboswitch
      RNA domain from the thermophilic Gram-positive bacterium Thermoanaerobacter
      tengcongensis are described. Experimental design based on screening multiple
      variant RNA sequences and techniques used to identify initial crystallization
      conditions were similar to those employed for most RNAs. However, serendipitous
      in-drop digestion of one RNA construct at a specific internucleotide linkage was
      crucial for the growth of high-quality glmS ribozyme crystals. Biochemical
      analysis of crystalline RNA identified the site of scission and guided design of
      an optimized bimolecular RNA construct. Finally, modifications of ionic strength
      and pH of solutions used for stabilization of the crystals were essential for
      optimal diffraction and binding of the activator glucosamine-6-phosphate,
      respectively. Although their details are specific to the glmS ribozyme, these
      general strategies may be useful for analyzing and improving crystals of other
      RNAs.

PMID- 19381559
TI  - Time-resolved NMR spectroscopy: ligand-induced refolding of riboswitches.
AB  - A detailed understanding of cellular mechanisms requires knowledge of structure
      and dynamics of the involved biomacromolecules at atomic resolution. NMR
      spectroscopy uniquely allows determination of static and dynamic processes at
      atomic level, including structured states often represented by a single state as
      well as by unstructured conformational ensembles. While a high-resolution
      description of structured states may also be obtained by other techniques, the
      characterization of structural transitions occurring during biomolecular folding
      is only feasible exploiting NMR spectroscopic methods. The NMR methodical
      strategy includes the fast initiation of a folding reaction in situ and the
      possibility to detect the induced process with sufficient time resolution on the
      respective NMR time scale. In the case of ligand-induced structural transitions
      of RNA, the initiation of the folding reaction can be achieved by laser-triggered
      deprotection of a photolabile caged ligand whose release induces folding of a
      riboswitch RNA. The strategy discussed here is general and can also be
      transferred to other biological processes, where at least one key reagent or
      substrate, e.g., ions, ligands, pH, or one specific conformational state, can be
      photochemically caged. The rates of reversible and irreversible reactions or
      structural transitions that can be covered by real-time NMR methods range from
      milliseconds up to hours.In this chapter, we discuss the application of a time
      resolved NMR strategy to resolve the ligand-induced folding of the guanine
      sensing riboswitch aptamer domain of the B. subtilis xpt-pbuX operon.

PMID- 19381558
TI  - Riboswitch conformations revealed by small-angle X-ray scattering.
AB  - Riboswitches are functional RNA molecules that control gene expression through
      conformational changes in response to small-molecule ligand binding. In addition,
      riboswitch 3D structure, like that of other RNA molecules, is dependent on cation
      RNA interactions as the RNA backbone is highly negatively charged. Here, we show
      how small-angle X-ray scattering (SAXS) can be used to probe RNA conformations as
      a function of ligand and ion concentration. In a recent study of a glycine
      binding tandem aptamer from Vibrio cholerae, we have used SAXS data and
      thermodynamic modeling to investigate how Mg(2+)-dependent folding and glycine
      binding are energetically coupled. In addition, we have employed ab initio shape
      reconstruction algorithms to obtain low-resolution models of the riboswitch
      structure from SAXS data under different solution conditions.

PMID- 19381560
TI  - Analysis of the RNA backbone: structural analysis of riboswitches by in-line
      probing and selective 2'-hydroxyl acylation and primer extension.
AB  - RNA sequences fold upon themselves to form complex structures. Functional
      analysis of most biological RNAs requires knowledge of secondary structure
      arrangements and tertiary base interactions. Therefore, rapid and comprehensive
      methods for assessing RNA structure are highly desirable. Computational tools are
      oftentimes employed for prediction of secondary structure. However, a greater
      degree of accuracy is achieved when these methods are combined alongside
      structure probing experimentation. Multiple probing techniques have been
      developed to assist identification of base-paired regions. However, most of these
      techniques investigate only a subset of RNA nucleotides at a time. A combination
      of structure probing approaches is thus required for analysis of all nucleotides
      within a given RNA molecule. Therefore, methods that investigate local structure
      for all positions in a sequence-independent manner can be particularly useful in
      characterizing secondary structure and RNA conformational changes. This chapter
      outlines protocols for two techniques, in-line probing and Selective 2'-Hydroxyl
      Acylation Analyzed by Primer Extension (SHAPE), which largely accomplish this
      goal.

PMID- 19381561
TI  - Identification of metabolite-riboswitch interactions using nucleotide analog
      interference mapping and suppression.
AB  - Riboswitches are RNA elements capable of modulating gene expression through
      interaction with cellular metabolites. One member of the riboswitch family, the
      glmS riboswitch, is unique among riboswitches in that it modulates gene
      expression by undergoing self-cleavage in the presence of its metabolite
      glucosamine-6-phosphate (GlcN6P). In order to investigate the interactions
      between the glmS RNA and GlcN6P we performed nucleotide analog interference
      mapping (NAIM) and suppression (NAIS). These techniques have been previously used
      to identify important functional groups in and tertiary contacts necessary for
      self-splicing and self-cleaving by catalytic RNAs, RNA-protein complexes, RNA
      folding, and RNA-metal ion interactions. Described here are the details of NAIM
      and NAIS experiments we have utilized to investigate RNA-ligand interactions
      between the glmS riboswitch and GlcN6P. These techniques can be employed to study
      a wide variety of RNA-small molecule interactions.

PMID- 19381562
TI  - RNA-dependent RNA switches in bacteria.
AB  - The versatility of RNA as a regulatory molecule has become increasingly apparent
      in recent years. RNA elements within a transcript can sense a large variety of
      physiological signals, resulting in modulation of expression of the gene(s)
      encoded on that transcript by effects on transcript synthesis, mRNA stability,
      and translation. The response of the transcript to the signal can result in
      direct sequestration of elements involved in various steps of gene expression, or
      promotion of a structural rearrangement of the target mRNA that affects the
      activity of elements important for expression. The regulatory signal can be as
      simple as a change in temperature, or as complex as a translating ribosome, the
      processivity of which is affected by the appropriate cellular parameter. Among
      these many regulatory mechanisms are those in which the regulatory signal is a
      specific RNA that binds to the target mRNA. Systems of this type are widespread
      in bacteria, and they fall into several classes based on the type of RNA that
      acts as the regulator, and the mode of interaction of the regulatory RNA with its
      target. These include systems in which the regulatory RNA is encoded on the
      opposite strand of its target, systems in which the regulatory RNA is encoded
      elsewhere in the genome, and systems in which RNAs (such as tRNAs) that are
      normally used for a different cellular process are borrowed for use as regulatory
      molecules. This review will summarize these classes of regulatory mechanisms and
      their use in bacterial systems.

PMID- 19381563
TI  - Probing mRNA structure and sRNA-mRNA interactions in bacteria using enzymes and
      lead(II).
AB  - Enzymatic probing and lead(II)-induced cleavages have been developed to study the
      secondary structure of RNA molecules either free or engaged in complex with
      different ligands. Using a combination of probes with different specificities
      (unpaired vs. paired regions), it is possible to get information on the
      accessibility of each nucleotide, on the binding site of a ligand (noncoding
      RNAs, protein, metabolites), and on RNA conformational changes that accompanied
      ligand binding or environmental conditions (temperature, pH, ions, etc.). The
      detection of the cleavages can be conducted by two different ways, which are
      chosen according to the length of the studied RNA. The first method uses end
      labeled RNA molecules and the second one involves primer extension by reverse
      transcriptase. We provide here an experimental procedure that was designed to map
      the structure of mRNA and mRNA-sRNA interaction in vitro.

PMID- 19381564
TI  - Structural probing of RNA thermosensors.
AB  - Chemical probing of RNA structure has become one of the most popular approaches
      to map the conformation of RNA molecules of various sizes under well-defined
      experimental conditions. The method monitors the sensitivity of each nucleotide
      to various chemicals, which reflects its hydrogen-bonding environment within the
      RNA molecule. The goal of this chapter is to provide the reader with an
      experimental guide to mapping the secondary structure of RNA thermosensors in
      vitro with the most suitable chemical probes.

PMID- 19381565
TI  - Ribosomal initiation complexes probed by toeprinting and effect of trans-acting
      translational regulators in bacteria.
AB  - Toeprinting was developed to study the formation of ribosomal initiation
      complexes in bacteria. This approach, based on the inhibition of reverse
      transcriptase elongation, was used to monitor the effect of ribosomal components
      and translational factors on the formation of the active ribosomal initiation
      complex. Moreover, this method offers an easy way to study in vitro how mRNA
      conformational changes alter ribosome binding at the initiation site. These
      changes can be induced either by environmental cues (temperature, ion
      concentration), or by the binding of metabolites, regulatory proteins, and trans
      acting RNAs. An experimental guide is given to follow the different steps of the
      formation of ribosomal initiation complexes in Escherichia coli and
      Staphylococcus aureus, and to monitor the mechanism of action of several
      regulators on translation initiation in vitro. Protocols to prepare the ribosome
      and the subunits are also given for Thermus thermophilus, Staphylococcus aureus,
      and Escherichia coli.

PMID- 19381566
TI  - Isolation and characterization of the heat shock RNA 1.
AB  - The heat shock (HS) response is the major cellular defense mechanism against
      acute exposure to environmental stresses. The hallmark of the HS response, which
      is conserved in all eukaryotes, is the rapid and massive induction of expression
      of a set of cytoprotective genes. Most of the induction occurs at the level of
      transcription. The master regulator, heat shock transcription factor (HSF, or
      HSF1 in vertebrates), is responsible for the induction of HS gene transcription
      in response to elevated temperature. Under normal conditions HSF is present in
      the cell as an inactive monomer. During HS, HSF trimerizes and binds to a
      consensus sequence in the promoter of HS genes, stimulating their transcription
      by up to 200-fold. We have shown that a large, noncoding RNA, HSR1, and the
      translation elongation factor eEF1A form a complex with HSF during HS and are
      required for its activation.

PMID- 19381567
TI  - Analysis of tRNA-directed transcription antitermination in the T box system in
      vivo.
AB  - Regulation of gene expression in bacteria by cis-acting RNA elements can be
      investigated both in vivo and in vitro. Analyses in vivo can focus on changes in
      mRNA transcript levels or in protein production. Systems that are regulated at
      the level of premature termination of transcription are best analyzed by
      monitoring expression of a fusion to an easily assayable reporter gene construct
      or by direct measurement of the terminated and readthrough transcripts. These
      experimental approaches are described in the context of the Bacillus subtilis T
      box mechanism, which responds to uncharged tRNA as the effector, and are readily
      adaptable to other regulatory systems that respond to other signal molecules, and
      other experimental systems.

PMID- 19381568
TI  - In vitro selection of conformational probes for riboswitches.
AB  - Riboswitches are non-coding RNA elements mainly located in the 5' untranslated
      regions (UTR) of bacterial genes. They bind to small metabolites and upon binding
      conformational changes occur that trigger the expression of a certain gene.
      Riboswitches have been identified that bind to amino acids, purines, and other
      small metabolites such as thiamine pyrophosphate. Riboswitches contain an aptamer
      domain which is necessary for interaction with the metabolite and a related
      expression domain which harbours structural and sequence information required for
      interference with gene expression. The binding of a metabolite to the aptamer
      domain induces structural rearrangements that are relayed to the expression
      domain, thereby interfering with gene expression. To investigate and determine
      domains of the riboswitches which undergo conformational changes upon metabolite
      binding we used a dynamic SELEX process and identified RNA aptamers that bind to
      the metabolite-free variant of the riboswitch but are released upon metabolite
      addition. By this means, and after determination of the binding region, domains
      which are necessary for proper function of a full-length riboswitch can be
      identified.

PMID- 19381569
TI  - A green fluorescent protein (GFP)-based plasmid system to study post
      transcriptional control of gene expression in vivo.
AB  - Small non-coding RNAs (sRNAs) are an emerging class of regulators of bacterial
      gene expression, which mainly modulate the translation of trans-encoded mRNAs.
      Typically, these molecules are 50-200 nucleotides in size and do not contain
      expressed open reading frames (ORFs). In Escherichia coli, about 70 members of
      this group have been identified to date and further estimates assume hundreds of
      sRNAs per bacterial genome. Regulation of gene expression by sRNAs is
      predominantly mediated by physical sRNA/target mRNA interactions that are based
      on short and imperfect complementarity. Although the contribution of sRNAs to
      overall bacterial gene regulation is now being appreciated, the function of many
      sRNAs is still unknown and their targets await to be uncovered. We recently
      developed a modular two-plasmid system, based on the green fluorescent protein
      (GFP) as non-invasive reporter of gene expression, to rapidly monitor the
      regulatory potential of sRNA/target mRNA pairs under investigation in vivo. The
      specialized reporter plasmid series also provides a suitable platform to study
      the function of cis-encoded riboregulators such as natural riboswitches,
      thermosensors, or engineered aptamer-based regulatory switches.

PMID- 19381570
TI  - High-throughput screens to discover synthetic riboswitches.
AB  - Synthetic riboswitches constructed from RNA aptamers provide a means to control
      bacterial gene expression using exogenous ligands. A common theme among
      riboswitches that function at the translational level is that the RNA aptamer
      interacts with the ribosome-binding site (RBS) of a gene via an intervening
      sequence known as an expression platform. Structural rearrangements of the
      expression platform convert ligand binding into a change in gene expression.
      While methods for selecting RNA aptamers that bind ligands are well established,
      few general methods have been reported for converting these aptamers into
      synthetic riboswitches with desirable properties. We have developed two such
      methods that not only provide the throughput of genetic selections, but also
      feature the quantitative nature of genetic screens. One method, based on cell
      motility, is operationally simple and requires only standard consumables; while
      the other, based on fluorescence-activated cell sorting (FACS), is particularly
      adept at identifying synthetic riboswitches that are highly dynamic and display
      very low levels of background expression in the absence of the ligand. Here we
      present detailed procedures for screening libraries for riboswitches using the
      two methods.

PMID- 19381571
TI  - A mammalian cell-based assay for screening inhibitors of RNA cleavage.
AB  - RNA cleavage is a catalytic reaction which defines many types of RNA processing
      events, including those of metabolite-sensing riboswitch, self-splicing introns,
      mRNA splicing, tRNA processing, polyA-cleavage, and various small ribozymes such
      as hairpin and hammerhead ribozyme. In this chapter, we describe a general
      methodology for developing a mammalian cell-based high-throughput screening assay
      useful for identifying small molecules capable of inhibiting RNA cleavage in
      mammalian cells. In the specific assay described, a plasmid DNA vector in which
      the expression of a luciferase reporter gene is controlled by hammerhead ribozyme
      cleavage was stably introduced into the human 293 cell line. Such a cell line
      enabled the rapid screening of chemical compound libraries and the identification
      of cell membrane-permeable inhibitory molecules capable of blocking ribozyme
      cleavage. The general strategy described later could in principle be adapted to
      identify small molecule inhibitors of many types of RNA cleavage reactions.

PMID- 19381572
TI  - In vitro selection of glmS ribozymes.
AB  - Riboswitches modulate gene expression in eubacteria and eukaryotes in response to
      changing concentrations of small molecule metabolites. In most examples studied
      to date, riboswitches achieve both metabolite sensing and gene control functions
      without the obligate involvement of protein factors. These findings validate the
      hypothesis that RNA molecules could be engineered to function as designer gene
      control elements that sense and respond to different ligands. We believe that
      reverse engineering natural riboswitches could provide an intellectual foundation
      for those who wish to build synthetic riboswitches. Also, natural riboswitches
      might serve as starting points for efforts to change ligand specificity or gene
      control function through mutation and selection in vitro. In this chapter, we
      describe how in vitro selection can be used to create variant glmS ribozymes.
      Additionally, we discuss how these techniques can be extended to other riboswitch
      classes.

PMID- 19381573
TI  - Two-dimensional electrophoresis: an overview.
AB  - Two-dimensional gel electrophoresis (2DE) separates proteins by molecular charge
      and molecular size. Proteins are first solubilised in a denaturing buffer
      containing a neutral chaotrope, a zwitterionic or neutral detergent, and a
      reducing agent. First-dimension isoelectric keywords, focusing, then subjects
      proteins to a high voltage within a pH gradient. The amphoteric nature of
      proteins means each migrates to the pH where the net molecular charge is zero.
      After equilibration, to ensure complete protein unfolding, the second dimension
      separates by molecular size. Each protein is therefore resolved at a unique
      isoelectric point/molecular size coordinate. After visualisation by staining
      proteome changes are revealed by gel image analysis, and protein spots of
      interest excised and identified by mass spectrometry sequence analysis combined
      with database comparison. Variations to this procedure include staining or radio
      labelling prior to electrophoresis. Although 2DE does have limitations, the most
      significant being the resolution of membrane and/or hydrophobic proteins, the
      potential solutions offered by pre-fractionation or adjustments to the
      electrophoresis regimen mean this technique is likely to remain central to
      proteomic research.

PMID- 19381574
TI  - Solubilization of proteins in 2DE: an outline.
AB  - Protein solubilization for two-dimensional electrophoresis (2DE) has to break
      molecular interactions to separate the biological contents of the material of
      interest into isolated and intact polypeptides. This must be carried out in
      conditions compatible with the first dimension of 2DE, namely isoelectric
      focusing. In addition, the extraction process must enable easy removal of any
      nonprotein component interfering with the isoelectric focusing. The constraints
      brought in this process by the peculiar features of isoelectric focusing are
      discussed, as well as their consequences in terms of possible solutions and
      limits for the solubilization process.

PMID- 19381575
TI  - Selection of pH ranges in 2DE.
AB  - This chapter describes the technical improvements of the two-dimensional
      electrophoresis pattern resulting of an optimized pH range in the first
      dimension. Various types of pH gradients are available. Different strategies can
      be applied in order to select the pH ranges for the exploration of a proteome.
      The resulting gels are analysed for their background, resolution, sensitivity in
      relation with the sample complexity. As the complete dynamic range of protein
      expression cannot be visualized, the high loading capacity of immobilized narrow
      pH gradients can be used. The limitations and possible enhancements are
      discussed.

PMID- 19381576
TI  - Difficult proteins.
AB  - The degree of protein diversity and dynamic range within organisms means that
      even the simplest proteome cannot be captured by any single extraction and
      separation step. New techniques have focused on major protein classes often under
      represented in proteome analysis; low abundance, membrane, and alkaline proteins.
      The last decade has seen considerable technology development in fractionation
      tools aimed at complexity reduction in many forms. The key outcome of complexity
      reduction is that each fraction, or sub-proteome, can be studied in more detail,
      and proteins which would have remained undetected in a total extract are present
      in sufficient quantities. However, the tools available are fractionations, not
      amplifications, and like all mining for rare and difficult items, a large amount
      of starting material is often required. The key shortcomings of many proteome
      analysis techniques are now well documented. With this knowledge, the best modern
      proteomics 'platform' involves combining multiple protein extractions, gel and
      chromatographic separations, and multiple MS analysis methods.

PMID- 19381577
TI  - Organelle proteomics.
AB  - The proteome of the cell is at the frontier of being too complex for proteomic
      analysis. Organelles provide a step up. Organelles compartmentalize the cell
      enabling a proteome, physiology and metabolism analysis in time and in space.
      Protein complexes separated by electrophoresis have been identified as the next
      natural level to characterize the organelles' compartmentalized membrane and
      soluble proteomes by mass spectrometry. Work on mitochondria and chloroplasts has
      shown where we are in the characterization of complex proteomes to understand the
      network of endogenous and extrinsic factors which regulate growth and
      development, adaptation and evolution.

PMID- 19381578
TI  - Applications of chemical tagging approaches in combination with 2DE and mass
      spectrometry.
AB  - Chemical modification reactions play an important role in various protocols for
      mass-spectrometry-based proteome analysis; this applies to both gel-based and gel
      free proteomics workflows. In combination with two-dimensional gel
      electrophoresis (2DE), the addition of "tags" by means of chemical reactions
      serves several purposes. Potential benefits include increased sensitivity or
      sequence coverage for peptide mass fingerprinting and improved peptide
      fragmentation for de novo sequencing studies. Tagging strategies can also be used
      to obtain complementary quantitative information in addition to densitometry, and
      they may be employed for the study of post-translational modifications. In
      combination with the unique advantages of 2DE as a separation technique, such
      approaches provide a powerful toolbox for proteomic research. In this review,
      relevant examples from recent literature will be given to illustrate the
      capabilities of chemical tagging approaches, and methodological requirements will
      be discussed.

PMID- 19381579
TI  - Immunoblotting 2DE membranes.
AB  - Two-dimensional electrophoresis (2DE) immunoblotting combines the resolving power
      of 2DE and the selectivity of antibodies, allowing the selection of individual or
      sets of proteins from the total proteome. It is essential when immunoblotting
      membranes that reproducible 2DE gels are obtained consistently. Afterwards, it is
      a matter of applying the same principles as 1DE immunoblotting. However, it
      should be noted that the most sensitive methods of detection should be used. This
      chapter outlines some of the considerations that should be taken into account,
      ranging from the choice and type of antibodies, buffers involved, and methods of
      detection and visualisation.

PMID- 19381580
TI  - Troubleshooting image analysis in 2DE.
AB  - The image analysis part of gel-based proteome research plays an important role in
      the overall success of the experiment. The main purpose of software-assisted 2DE
      gel analysis is to detect the protein spots, match them between gels within an
      experiment, and identify any differences in protein expression between sets of
      samples. Efficient analysis of protein expression relies on automated image
      processing techniques. There are several factors to consider in the choice of
      software product, as well as in the implementation of the analysis itself.
      Successful quantification of protein expression levels is largely dependent on
      the algorithms for spot matching, normalization, and background subtraction
      provided by the 2DE analysis software. In addition to generic protocols for image
      acquisition and subsequent 2DE image analysis (using Progenesis PG200), this
      chapter describes methods for quantitative and qualitative evaluation of the
      quality of the image analysis.

PMID- 19381581
TI  - Analysis of bacterial proteins by 2DE.
AB  - Two-dimensional gel electrophoresis (2DE) is a key analytical method for
      investigating bacterial -proteomes. The relatively simple genomes of many
      bacteria combined with only limited post--translational modifications of
      bacterial proteins mean that a significant proportion of the proteome is open to
      analysis by 2DE. The applications of 2DE in the field of microbiology are diverse
      and range from analysing physiological responses of the bacteria to environmental
      stress to investigating bacterial pathogenesis in human bacterial pathogens. The
      standard approach for 2DE in the analysis of bacterial proteins uses immobilised
      pH gradient (IPG) gels in the first dimension for charge separation and then an
      orthogonal separation, in the presence of SDS, to resolve the proteins according
      to their molecular mass. Protocols are presented in this chapter for small (7-cm
      length IPG gel strips)- and medium (11- or 13-cm-length IPG strips)-format 2D
      gels using IPG gels and SDS-containing polyacrylamide slab gels for the second
      dimension. The application of the methods are demonstrated for the analysis of
      cell lysates prepared from Helicobacter pylori, although the same protocols have
      been used to analyse proteins from a variety of human bacterial pathogens.

PMID- 19381582
TI  - Proteomic analysis of Caenorhabditis elegans.
AB  - Proteomic studies of the free-living nematode Caenorhabditis elegans have
      recently received great attention because this animal model is a useful platform
      for the in vivo study of various biological problems relevant to human disease.
      In general, proteomic analysis is carried out in order to address a specific
      question with respect to differential changes in proteome expression under
      certain perturbed conditions. In this chapter, we focus on gel-based proteomic
      analysis of C. elegans subjected to two specific stress conditions during
      development: induction of the dauer state for whole body protein expression and a
      temperature shift for egg protein expression. Utilizing these differently
      perturbed C. elegans protein samples, two-dimensional electrophoresis and
      differential in-gel electrophoresis methods have led to the discovery of
      remarkable aspects of the worm's biology. We also provide numerous details about
      the technical points and protocols necessary for successful experimentation.

PMID- 19381583
TI  - Protein extraction for 2DE.
AB  - Our protein extraction protocol for two-dimensional gel electrophoresis (2DE) was
      updated to meet current needs in the field of proteomics. This protocol
      summarizes our experience using this method since its introduction over 30 years
      ago. We provide a total as well as fractionated extraction protocol. The former
      is easy and fast to use, suitable for most standard 2DE applications, whereas the
      latter is used for special applications such as the extraction of membrane or
      nuclear proteins.Both extraction protocols stress the need that protease
      inhibitors are added early to still deep frozen tissue to preclude an activation
      of proteases which destroy proteins and make them inaccessible to analysis. We
      also emphasize that, to remain soluble, proteins need to stay in an environment
      resembling a living cell as closely as possible. Sample dilution is therefore
      kept to a minimum and the pH of the extract is close to in vivo conditions at pH
      7.1. In addition there are no precipitation/resolubilization steps which could
      irreversibly remove proteins from the extract. Furthermore, the total extraction
      does not even require centrifugation. Our extraction protocol is compatible with
      recent advances in 2DE-staining techniques such as differential in gel
      electrophoresis and fluorescence staining as well as mass spectrometry.

PMID- 19381584
TI  - Analysis of proteins from marine molluscs.
AB  - Application of the two-dimensional gel electrophoresis (2DE) protocols which were
      developed for samples of mammalian origin gives unsatisfactory results when used
      in samples from marine molluscs. This chapter describes a detailed protocol of
      2DE that can be applied to these organisms, especially for Ruditapes decussatus
      and Bathymodiolus azoricus.

PMID- 19381585
TI  - Preparation and analysis of plant and plastid proteomes by 2DE.
AB  - Most proteomic analyses require prefractionation and protein purification
      strategies to achieve maximal proteome coverage, especially in plants in which
      cells often have a few highly abundant proteins and substances like polyphenols
      or secondary metabolites that can have significant impact on proteome coverage.
      Several methods have been developed to reduce cellular complexity and increase
      protein dynamic range. One approach is the display of the plant cell proteome on
      a single two-dimensional gel. Other approaches use fractionation strategies to
      reduce sample complexity to a subset of functionally related proteins or pathway
      modules. Here we describe a strategy to separate the proteome of a purified cell
      organelle using two-dimensional gel electrophoresis (2DE). The proteome of plant
      chloroplasts and nonphotosynthetic plastids was further fractionated by a
      differential protein solubilization method that is fully compatible with 2DE. The
      final protein complement of individual fractions comprised approximately 1,000
      different protein species that can be fully resolved and visualized in a single
      2DE gel.

PMID- 19381586
TI  - High-resolution 2DE.
AB  - About 30 years ago two-dimensional gel electrophoresis (2DE) was developed
      independently by Klose and O'Farrell representing the combination of two
      orthogonal separation techniques. In the first dimension the proteins are
      separated by isoelectric focusing (IEF) according to their isoelectric point. In
      the second dimension proteins are separated according to their electrophoretic
      mobility by conventional SDS-PAGE. For IEF two different techniques, immobilized
      pH gradient (IPG) and carrier-ampholyte-based IEF (CA-based IEF), respectively,
      are currently applied. With a resolution of up to 10,000 protein spots in one
      gel, 2DE offers a huge potential to give a comprehensive overview of the proteins
      present in the examined system. In combination with image analysis and mass
      spectrometry 2DE is still the method of choice to analyse complex protein
      samples.In this chapter we provide detailed protocols for both 2DE systems and
      give an overview about the latest developments including the two-dimensional
      difference gel electrophoresis (DIGE) system.

PMID- 19381587
TI  - Blue native-gel electrophoresis proteomics.
AB  - The importance of the mitochondrion in maintaining normal cellular physiology has
      long been appreciated. Recently there has been an upsurge in mitochondrial
      research due to increased recognition that a number of diseases are caused by
      defective functioning of this key intracellular organelle. Given this, along with
      advances made in proteomics technologies, the mitochondrion is clearly recognized
      as a top candidate for proteomics analysis. However, mitochondrial proteomics is
      not a trivial undertaking due to physicochemical properties that impair the
      resolution of inner mitochondrial membrane proteins when using conventional
      proteomic gel electrophoresis procedures. To circumvent such problems, many
      laboratories have adapted blue native-gel electrophoresis (BN-PAGE), a
      specialized type of native-gel electrophoresis, to generate high-resolution
      proteomic maps of the oxidative phosphorylation system. In this short overview
      the concepts and methods of BN-PAGE are presented, which demonstrate the power of
      using this complementary proteomics approach to identify alterations in the
      mitochondrial proteome that contribute to disease.

PMID- 19381588
TI  - 2DE for proteome analysis of human metaphase chromosomes.
AB  - Two-dimensional electrophoresis (2DE) is one of the most effective methods for
      the reliable separation of proteins in a single gel. In our proteome analyses of
      human chromosomes, we used two types of 2DE: two-dimensional isoelectric focusing
      SDS-polyacrylamide gel electrophoresis (2D IEF/SDS-PAGE) and radical-free and
      highly reduced two-dimensional polyacrylamide gel electrophoresis (RFHR 2D PAGE)
      together with one-dimensional SDS-polyacrylamide gel electrophoresis (1DE).
      Experimental details of these gel electrophoresis procedures that have been shown
      to be effective for human proteome analyses are described in detail.

PMID- 19381589
TI  - Microsomal proteomics.
AB  - Proteomic profiling of subcellular compartments has many advantages over
      traditional proteomic approaches using whole cell lysates as it allows for
      detailed proteome analysis of a specific organelle and corresponding functional
      characteristics. The microsome is a critical, membranous compartment involved in
      the synthesis, sorting, and secretion of proteins as well as other metabolic
      functions. This chapter will describe detailed methods for the isolation of
      microsomal organelles including the ER, Golgi, and prechylomicron transport
      vesicle (PCTV), a recently identified vesicular system involved in intestinal
      lipoprotein assembly and secretion. Particular focus is given to the isolation of
      microsomes from primary hepatocytes and enterocytes freshly isolated from rodent
      liver and intestinal tissue, and their proteomic profiling using a combination of
      two-dimensional gel electrophoresis and mass spectrometry.

PMID- 19381590
TI  - Prefractionation using microscale solution IEF.
AB  - Proteomics often involves systematic analyses of proteomes that are constantly
      changing in response to changes in the environment of the cell, tissue, or
      organism being analyzed. Due to limitations of all current protein profiling
      methods, powerful, reliable proteome prefractionation methods prior to two
      dimensional electrophoresis (2DE) gels or alternative non-2DE gel methods are
      needed for in-depth quantitative comparisons of the complex proteomes typically
      encountered with samples from higher eukaryotes. The microscale solution
      isoelectrofocusing (MicroSol IEF) fractionation method is capable of reproducibly
      dividing complex proteomes into as many as seven well-resolved fractions based on
      the proteins' pIs on a small volume scale ( approximately 0.65mL/fraction). When
      MicroSol IEF is combined with narrow pH range 2DE gels or with alternative
      downstream analysis methods, it can substantially increase the detection dynamic
      range and the total number of proteins that can be quantitatively compared.
      Although MicroSol IEF is reasonably reproducible, subtle variations can occur in
      different separations similar to the minor variations often seen in most
      separations of proteins. Therefore, for reliable quantitative comparisons the
      samples to be compared should be differentially labeled with either Cy dyes or
      stable isotope labels prior to mixing and separation in a single MicroSol IEF
      run. Larger numbers of samples can be compared across many MicroSol IEF
      separations by using a differentially labeled internal standard composed of equal
      aliquots of all samples to be compared.

PMID- 19381591
TI  - Diagonal electrophoresis for detection of protein disulphide bridges.
AB  - A state of oxidative stress (OS) can occur when there is an imbalance between the
      rate of reactive oxygen species (ROS) production and their detoxification. Under
      OS conditions sulphur-containing residues are particularly susceptible to
      oxidation, and this can result in transient formation of intra- or inter-chain
      disulphide bridges. Diagonal electrophoresis is a relatively simple technique to
      analyse the formation of these bridges by sequential non-reducing/reducing
      electrophoresis. Proteins that do not form disulphides, electrophorese
      identically in both dimensions and form a diagonal after the second dimension,
      proteins that contained intra-chain disulphides lie above this diagonal, while
      those that formed inter-disulphides fall below the diagonal. These spots can be
      excised, tryptic digested, and identified by mass spectrometry. Identification of
      those proteins, which are reversibly modified, could play an important part in
      coupling redox status to protein function.

PMID- 19381592
TI  - High-resolution large-gel 2DE.
AB  - Our two-dimensional gel electrophoresis (2DE) protocol has been continuously
      improved in our laboratory since its inception 30 years ago. An updated version
      is presented here. This protocol is a result of our experience in proteome
      analysis of tissue extracts, cultured cells (mammalian, yeast, and bacteria),
      cellular organelles, and subcellular fractions. Many modifications and
      suggestions emerging in our lab as well as in the literature were tested and
      integrated into our improved protocol if helpful. Importantly we use (a) large
      (46 x 30 cm) gels to achieve a high resolution and (b) ready-made gel solutions
      produced in large batches and stored frozen, a prerequisite, among others, for
      our very high reproducibility. Employing the 2DE method described here we
      demonstrated that protein patterns separating more than 10,000 protein spots can
      be obtained from mouse tissue. This is the highest resolution reported in the
      literature for 2DE of complex protein mixtures so far. Our 2DE patterns are of
      high quality with regard to spot shape and intensity as well as background. The
      reproducibility of the protein patterns is shown to be extremely satisfactory.
      New staining methods such as differential in gel electrophoresis (DIGE) and the
      latest 2DE gel evaluation software are compatible to our 2DE protocol. Using
      suitable staining protocols proteins can easily be identified by mass
      spectrometry.

PMID- 19381593
TI  - Silver staining of proteins in 2DE gels.
AB  - Silver staining detects proteins after electrophoretic separation on
      polyacrylamide gels. Its main positive features are its excellent sensitivity (in
      the low nanogram range) and the use of very simple and cheap equipment and
      chemicals. The sequential phases of silver staining are protein fixation, then
      sensitization, then silver impregnation, and finally image development. Several
      variants of silver staining are described here, which can be completed in a time
      range from 2 h to 1 day after the end of the electrophoretic separation. Once
      completed, the stain is stable for several weeks.

PMID- 19381594
TI  - Detection of 4-hydroxy-2-nonenal- and 3-nitrotyrosine-modified proteins using a
      proteomics approach.
AB  - Oxidative stress has been shown to be one of the mechanisms involved in a number
      of diseases, including neurodegenerative disorders, ischemia, cancer, etc.
      Oxidative stress occurs mainly due to an imbalance between oxidant and
      antioxidant systems. Oxidants can damage virtually all biological molecules
      including DNA, RNA, cholesterol, lipids, carbohydrates, proteins, and
      antioxidants. The oxidative modification of proteins has been shown to play an
      important role in a number of human diseases. And the methods to identify
      specific proteins that are susceptible to 4-hydroxy 2-nonenal (HNE) and 3
      nitrotyrosine (NT) modifications are limited and difficult. Our laboratory uses
      two-dimensional polyacrylamide gel electrophoresis (2DE) in combination with
      western blotting to identify the specific targets of protein nitration and lipid
      peroxidation. This may require the analysis of thousands of individual proteins
      from cells and tissues, and coupling of mass spectrometry to this technique
      allows the identification of proteins. Since the protein levels and the protein
      oxidation can be obtained from 2DE and 2D blots, specific nitration or HNE
      modification of each protein spot can be easily calculated.

PMID- 19381595
TI  - Proteomic detection of oxidized and reduced thiol proteins in cultured cells.
AB  - The oxidation and reduction of cysteine residues is emerging as an important post
      translational control of protein function. We describe a method for fluorescent
      labelling of either reduced or oxidized thiols in combination with two
      dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (2DE) to
      detect changes in the redox proteome of cultured cells. Reduced thiols are
      labelled with the fluorescent compound 5-iodoacetamidofluorescein. To monitor
      oxidized thiols, the reduced thiols are first blocked with N-ethyl-maleimide,
      then the oxidized thiols reduced with dithiothreitol and labelled with 5
      iodoacetamidofluorescein. The method is illustrated by treating Jurkat T-lymphoma
      cells with hydrogen peroxide and monitoring increased labelling of oxidized thiol
      proteins. A decrease in labelling can also be detected, and this is attributed to
      the formation of higher oxidation states of cysteine that are not reduced by
      dithiothreitol.

PMID- 19381596
TI  - Detection of ubiquitination in 2DE.
AB  - Ubiquitination involves the tagging of proteins with one (mono-) or more (poly-)
      ubiquitin molecules. Primarily the role of ubiquitination involves mainly short
      lived and regulatory proteins being tagged with a poly-ubiquitin tail, thus
      introducing a hydrophobic patch that allows the protein to be identified and
      degraded by the 26S proteasome. Transfer of ubiquitin to the lysine residue of a
      target protein is a multi-step ATP-dependent process. The functions of
      ubiquitination have been extended in recent years to all areas of biology, many
      of them proteasome independent. As a small fraction of any protein may
      potentially be ubiquitinated, this may explain the wide range and large number of
      proteins that have been identified as being tagged with ubiquitin in the
      literature. This chapter outlines a general method for an indication of
      ubiquitination levels and identification of ubiquitinated proteins by two
      dimensional electrophoresis in combination with immunoblotting.

PMID- 19381597
TI  - Phosphoproteome analysis by in-gel isoelectric focusing and tandem mass
      spectrometry.
AB  - Protein phosphorylation is central to most signaling events in eukaryotic cells.
      Large-scale analysis of protein phosphorylation in vivo is a highly challenging
      undertaking that requires powerful analytical and bioinformatics tools; numerous
      phosphoproteomic methodologies that use various combinations of these tools have
      been developed recently. This chapter describes an in-gel isoelectric focusing
      liquid chromatography-tandem mass spectrometry (IEF-LC-MS/MS) analytical strategy
      for phosphoproteome mapping. The strategy encompasses seven steps: (1) extraction
      of proteins from the biological system under study (e.g., a tissue); (2)
      separation of the protein mixture by isoelectric focusing in an immobilized pH
      gradient (IPG) strip; (3) protein fixation followed by sectioning of the IPG
      strip; (4) digestion of the proteins in each gel section; (5) enrichment of
      phosphopeptides in the digests by immobilized metal ion affinity chromatography;
      (6) analysis of the enriched digests by LC-MS/MS; and (7) identification of the
      phosphopeptides/proteins through database searches, and assignment of the sites
      of phosphorylation in these proteins.

PMID- 19381598
TI  - Detection of protein glutathionylation.
AB  - Recent studies indicate that protein glutathionylation is an important regulatory
      mechanism. The develop-ment of redox proteomics techniques to identify proteins
      undergoing glutathionylation has a key role in defining the importance of this
      post-translational modification, although the available methods are not yet
      comparable to those for the study of other modifications like phosphorylation. We
      describe here methods that have been successfully employed to identify in vitro
      glutathionylated proteins.

PMID- 19381600
TI  - Active protease mapping in 2DE gels.
AB  - Proteases act as the molecular mediators of many vital biological processes. To
      understand the function of each protease, it needs to be separated from other
      proteins and characterized in its natural, biologically active form. In the
      method described in this chapter, proteases in a biological sample are separated
      under nonreducing conditions in 2DE gels. A specific small protease substrate,
      tagged with a fluorescent dye, is copolymerized into the SDS gel in the second
      dimension. After electrophoresis, the proteins are renatured by washing the gel
      with Triton X-100 solution or Milli Q water to remove SDS. The gel is then
      incubated in a protease assay buffer. The hydrolysis of the tagged specific
      substrate by the renatured protease releases the free fluorescent dye, which
      fluoresces in situ. The fluorescent spots indicate the location of the specific
      proteases in the gel and the specificity of the proteases.

PMID- 19381599
TI  - Activity-based protein profiling of protein tyrosine phosphatases.
AB  - The ability to accurately monitor the dynamics involved with the activity and
      state of a specific protein population in a complex biological system represents
      one of the major technological challenges in studying systems biology. Over the
      past several years a number of groups have attempted to spearhead this new
      frontier of systems biology by developing enzyme family-specific activity-based
      chemical probes linked to appropriate reporter groups that by nature only target
      and subsequently tag the active form of these enzymes. In this work, we will
      highlight the methods used to characterize activity-based probes as to their
      utility in biological contexts. Specifically, we will address activity-based
      protein profiling of the protein tyrosine phosphatases, a highly conserved enzyme
      family responsible for the phospho-tyrosine hydrolysis reaction, a ubiquitous
      reaction that is absolutely essential to the regulation of a myriad of cellular
      processes.

PMID- 19381601
TI  - Two-dimensional difference gel electrophoresis.
AB  - The introduction of two-dimensional fluorescent difference gel electrophoresis
      has enabled the extensive screening of differential protein expression levels
      with higher confidence and greater sensitivity than using the classical two
      dimensional electrophoresis (2DE) approach. Using this technology, multiple
      protein samples can be labeled with up to three different fluorescent dyes. These
      labeled protein samples are mixed and applied on the same 2DE gel, subsequently
      scanned and analyzed by specialized software tools. The possibility to run two or
      more protein samples on a single gel, as well as the introduction of an internal
      standard on each gel drastically reduces the gel-to-gel variability and thus
      results in higher levels of certainty with regard to the differential character
      of the expressed proteins.

PMID- 19381602
TI  - Protein expression profiling.
AB  - Protein expression profiling is defined in general as identifying the proteins
      expressed in a particular tissue, under a specified set of conditions and at a
      particular time, usually compared to expression in reference samples. This
      information is useful in drug discovery and diagnosis as well as in understanding
      response mechanisms at the protein level. We may identify all the proteins
      responding to a particular stimulus and select those whose expression changes
      most. Or we may isolate significant protein variables and then identify them.
      These definitive sets of proteins (protein expression signatures; PES) are
      specific to diseases, toxicants, physical stresses, and to degrees of stress
      severity. Here we describe a method, based on machine learning, for isolating the
      sets of proteins, before identifying them by name, which classify accurately the
      treatment classes in a study. The principle in this chapter is that if proteins
      associated with known classes of interest can be used to identify unknown classes
      then the proteins are definitive for diagnosis.The proteins in each class,
      including controls, are converted to digital data and serve as input to
      artificial neural network (ANN) models. Multiple two-dimensional electrophoresis
      (2DE) gel patterns are included in each treatment class. A training subset of
      digitized individual, not composite, gel images is used to construct an ANN model
      which is then applied to a test set of images. Successful classification of the
      unknown (test) data confirms that the variables included in the model are indeed
      significant in discrimination among the classes. In the study described here the
      misclassifications were 5% or less using the ANN models. The ANN method seems to
      be a useful complement to image analysis, described in Chapter "Troubleshooting
      Image Analysis in 2DE". The reduction in protein variables permits multivariable
      statistics such as cluster and discriminant analyses.

PMID- 19381603
TI  - C-terminal sequence analysis of 2DE-separated proteins.
AB  - The overall study of post-translational modifications (PTMs) of proteins is
      gaining strong interest. Beside phosphorylation and glycosylation, truncations of
      the nascent polypeptide chain at the N- or C-terminus are by far the most common
      types of PTMs. Nevertheless, little attention has been paid to the development of
      approaches that allow a systematic analysis of these proteolytic processing
      events. Here we present a protocol that allows the identification of the C
      terminal sequence of proteins separated by two-dimensional polyacrylamide gel
      electrophoresis (2DE). For each purified protein, a peptide mixture is generated
      by cleavage of the protein with cyanogen bromide. During incubation with
      carboxypeptidases only the original C-terminal fragment forms a ladder. Ladder
      readout is performed using MALDI mass spectrometry. 2DE-separated proteins from
      Shewanella oneidensis were chosen as a model system to investigate the
      effectiveness of the approach.

PMID- 19381604
TI  - Shotgun protein analysis by liquid chromatography-tandem mass spectrometry.
AB  - Two-dimensional electrophoresis (2DE) is an excellent technology for the analysis
      of complex protein mixtures, but it has drawbacks, such as hardly detecting very
      hydrophobic proteins. Shotgun protein analysis is one of the major technologies
      used to compensate for the weaknesses of 2DE. In this approach, total proteins
      are digested as a mixture and the digested peptides are separated by one
      dimensional or multidimensional chromatography and introduced into a tandem mass
      spectrometer. Since the shotgun approach is the primary strategy in proteomics
      besides 2DE, a great number of related methodologies have been developed. In this
      chapter, we would like to introduce the simplest protocol, in which proteins are
      digested in solution and the digested peptides are analyzed by one-dimensional
      reversed-phase liquid chromatography coupled with tandem mass spectrometry (LC
      MS/MS), as a starting point for shotgun protein analysis.

PMID- 19381605
TI  - De novo sequence analysis of N-terminal sulfonated peptides after in-gel
      guanidination.
AB  - In this protocol, we describe an approach in which two-dimensional
      electrophoresis (2DE)-separated proteins are guanidinated in-gel prior to
      enzymatic cleavage. In contrast to previously described techniques, this
      procedure allows the extracted tryptic peptides to be N-terminally sulfonated
      without any further sample purification. The protocol was applied on a proteomic
      study of 2DE-separated proteins from Halorhodospira halophila, an extremophilic
      eubacterium with an unsequenced genome at the moment of analysis.

PMID- 19381606
TI  - Tryptic digestion of in-gel proteins for mass spectrometry analysis.
AB  - Identification and characterization of proteins are ultimately the goal in
      proteomic analysis. In order to identify a protein trypsin is commonly used to
      digest protein into peptides which can be analyzed by matrix-assisted laser
      desorption ionization mass spectrometry (MALDI-MS) or liquid chromatography
      tandem mass spectrometry (LC-MS/MS). This chapter describes a tryptic digestion
      method for digestion of proteins in one-dimensional (1DE) or two-dimensional
      (2DE) polyacrylamide gels. The method involves cutting target protein bands or
      spots, removal of protein stain, reduction and alkylation of native protein,
      digestion and finally extraction of peptides for mass spectrometry analysis. The
      method is simple and reasonably sensitive that many in-gel proteins that are
      barely visible with Coomassie blue stain have been successfully identified.

PMID- 19381607
TI  - Database interrogation algorithms for identification of proteins in proteomic
      separations.
AB  - Protein identification is a key aspect in the investigation of proteomes.
      Typically, in a 2-DE gel-based proteomics analysis, the spots are enzymatically
      digested and the resulting peptide masses are measured, producing mass spectra.
      Peptides can also be isolated and fragmented within the mass spectrometer,
      leading to tandem mass spectra. For protein and peptide identification, an
      algorithm matches the mass spectra and other empirical information against a
      protein database to define if a protein is already known or novel. A variety of
      different programs for protein identification with database interrogation has
      been developed. This chapter focuses on the use of the software Aldente and
      Phenyx, for MS and tandem MS identification, respectively.

PMID- 19381608
TI  - Creating 2DE databases for the World Wide Web.
AB  - With the development of the Internet, a growing number of two-dimensional
      electrophoresis (2DE) databases have become available (60 in 2009, for a total of
      425 image maps). By linking the two components constituting 2DE databases, gel
      images and protein information, the active hypertext links provide a powerful
      tool for data integration, in addition to navigation from one database to
      another.This chapter shows how to prepare the necessary files to build a
      federated 2DE database in order to make it available over the Internet and how to
      further update it.

PMID- 19381609
TI  - [Transplantation medicine 2009].

PMID- 19381610
TI  - Arthroscopic removal of the failed silicone radial head prosthesis.
AB  - Although silicone radial head arthroplasty has been successful in many patients,
      it has been associated with complications such as fractures of the prosthesis and
      silicone synovitis. Synovectomy and removal of the failed silicone radial head,
      with or without reimplantation of a metallic radial head, is indicated in such
      complications. In an effort to perform minimally invasive surgery, we performed
      arthroscopic removal of the silicone head combined with synovectomy in a series
      of such patients. The silicone prostheses were cut into two or three pieces and
      then removed. After a median follow up of 26 months, all patients reported
      excellent pain relief and there were no residual loose bodies. Removal of a
      failed silicone radial head can be successfully performed arthroscopically. This
      arthroscopic technique has the advantage of being minimally invasive and can be
      combined with other procedures including capsulectomy, if necessary.

PMID- 19381611
TI  - Septic knee arthritis following ACL reconstruction: a systematic review.
AB  - Although postoperative septic arthritis is rare after ACL reconstruction, it
      carries a high morbidity that results in poor clinical outcome. Despite low
      incidence, it is important to recognize that infection and treat it without delay
      because of devastating consequences, such as loss of hyaline cartilage and
      arthrofibrosis, in order to avoid osteoarthritis development and near full range
      of motion achieved. Herein we discuss the pathogenesis, risk factors, clinical
      presentation, diagnostic evaluation, treatment protocols and complications of
      septic knee arthritis after ACL reconstruction.

PMID- 19381612
TI  - Total knee arthroplasty: better short-term results after subvastus approach: a
      randomized, controlled study.
AB  - The purpose of this study was to evaluate the short-term results after performing
      a total knee arthroplasty (TKA) using two surgical approaches: the subvastus
      approach (SV) and the conventional parapatellar approach. It was hypothesized
      that the SV approach would achieve the best short-term benefits. This is a
      randomized prospective and double-blind study that includes 104 patients.
      Evaluations were carried out preoperatively, when discharged (5 days) at one,
      three, and 12 postoperative months. The SV group showed significantly better
      range of movement and quadriceps extensor force when discharged. Statistically
      significant differences were found that showed a distinct improvement in favour
      of the SV group at one month in terms of extensor force and according to the
      Barthel Index. No significant difference was found between the two groups at the
      12 month evaluation. It was concluded that the SV approach offers superior short
      term clinical and functional results and it was shown that this approach also
      offers a significant advantage to the patient in the immediate postoperative
      period, although these differences tend to disappear over time following TKA. We
      strongly recommend the SV approach in the majority of TKA.

PMID- 19381613
TI  - Osteoarthritis? Ochronotic arthritis! A case study and review of the literature.
AB  - Alkaptonuria is a rare disease in which the body does not have enough of an
      enzyme called homogentisic acid oxidase. Osteoarthritis is the most common
      degenerative joint disease. Ochronotic arthritis which resulting from the
      deposition of oxidized homogentisic acid within the connective tissues of
      peripheral joints has clinical feature that resembles those of osteoarthritis,
      but it has a unique manifestation. We reported a case of a patient of ochronotic
      arthritis, arthroscopic findings showed large areas of darkly pigmented full
      thickness cartilage defects in the right knee, the whole meniscal parenchymatous
      tissue was also darkly pigmented. Histological investigation proved to be
      ochronosis.

PMID- 19381614
TI  - Appraisal of the sensitising potential of orally and dermally administered
      mercaptobenzothiazole by a biphasic protocol of the local lymph node assay.
AB  - Mercaptobenzothiazole (MBT) is used while manufacturing natural rubber products.
      Our study deals with assessing its allergenic potential following dermal and oral
      routes of exposure, using a biphasic local lymph node assay (LLNA). Female Balb/c
      mice were treated with MBT (dermally 3, 10, 30% concentrations in DMSO; orally 1,
      10, 100 mg/kg doses in corn oil) on the back (dermal study) or through oral
      administration (oral study) on days 1-3 followed by auricular application of 3,
      10 and 30% concentrations, respectively, on days 15-17. End points determined on
      day 19 included ear thickness, ear punch weight, lymph node weight, lymph node
      cell count, and lymphocyte subpopulations (CD4+, CD8+, CD45+). After dermal
      application of 3% or 10% solution, a significant increase in cell count and lymph
      node weight along with significant decrease in CD8+ cells was observed. After
      initial oral administration of 1 mg/kg, we noticed a significant amplification in
      cell count. Following oral administration of 10 mg/kg, we observed a similar
      increase in cell count and lymph node weight. The results of our study show that
      the modified biphasic LLNA protocol can be used to study the sensitising
      potential of a compound also following the oral route of exposure.

PMID- 19381615
TI  - Simultaneous on-line size and chemical analysis of gas phase and particulate
      phase of cigarette mainstream smoke.
AB  - This paper describes the combined set-up of on-line chemical analysis of gas
      phase by single-photon ionisation/resonance enhanced multiphoton ionisation-time
      of-flight mass spectrometry (SPI/REMPI-TOFMS) and on-line particle size analysis
      by differential electrical mobility particle spectrometry (DMS 500) for the
      investigation of fresh cigarette mainstream smoke. SPI is well suited for the
      investigation of a great variety of organic species, whereas REMPI is highly
      sensitive for aromatic compounds. Gas phase measurements of filtered and
      unfiltered smoke are possible with the SPI/REMPI-TOFMS in order to determine the
      influence of the presence of particles on the chemical composition of the gas
      phase. Initial results are shown for the characterisation and comparison of three
      pure Virginia tobacco research cigarettes having filter ventilations of 0%, i.e.
      no filter ventilation, 35% and 70% ventilation. The three cigarette types are
      smoked under two different smoking regimes, a standard regime using puff
      parameters equivalent to the conventional International Standard Organisation
      regime and a more intense smoking regime. For the gas phase, qualitative puff-by
      puff resolved yields of three selected compounds (acetaldehyde, phenol and
      styrene) are shown and compared. For particulate matter, particle number, count
      median diameter and total surface area are illustrated on a puff-by-puff basis.
      Yields of the chemicals analysed, puff number and surface area are in good
      agreement with the intensity of the smoking regime and the dilution of smoke by
      filter ventilation. However, gaseous compounds are influenced differently,
      depending whether an absolute particle filter is present or not, i.e. they can be
      totally removed (phenol), partially removed (styrene) or not affected
      (acetaldehyde). For particle analysis, the count median diameter decreases from
      puff to puff and is strongly dependent on the smoking regime and ventilation
      rate. Thereby, 0% ventilated cigarettes smoked under the intense regime result in
      the smallest count median diameters of ca. 180 nm, whereas 70% ventilated
      cigarettes smoked with a standard regime lead to the largest values of up to 280
      nm. As particle diameter increases, particle number decreases as a consequence of
      increasing time for particle coagulation.

PMID- 19381616
TI  - Focus on RNA analysis.

PMID- 19381617
TI  - Tip-enhanced Raman spectroscopy for nanoscale strain characterization.
AB  - Tip-enhanced Raman spectroscopy (TERS), which utilizes the strong localized
      optical field generated at the apex of a metallic tip when illuminated, has been
      shown to successfully probe the vibrational spectrum of today's and tomorrow's
      state-of-the-art silicon and next-generation semiconductor devices, such as
      quantum dots. Collecting and analyzing the vibrational spectrum not only aids in
      material identification but also provides insight into strain distributions in
      semiconductors. Here, the potential of TERS for nanoscale characterization of
      strain in silicon devices is reviewed. Emphasis will be placed on the key
      challenges of obtaining spectroscopic images of strain in actual strained silicon
      devices.

PMID- 19381618
TI  - Surface-enhanced Raman spectroscopy: substrate-related issues.
AB  - After over 30 years of development, surface-enhanced Raman spectroscopy (SERS) is
      now facing a very important stage in its history. The explosive development of
      nanoscience and nanotechnology has assisted the rapid development of SERS,
      especially during the last 5 years. Further development of surface-enhanced Raman
      spectroscopy is mainly limited by the reproducible preparation of clean and
      highly surface enhanced Raman scattering (SERS) active substrates. This review
      deals with some substrate-related issues. Various methods will be introduced for
      preparing SERS substrates of Ag and Au for analytical purposes, from SERS
      substrates prepared by electrochemical or vacuum methods, to well-dispersed Au or
      Ag nanoparticle sols, to nanoparticle thin film substrates, and finally to
      ordered nanostructured substrates. Emphasis is placed on the analysis of the
      advantages and weaknesses of different methods in preparing SERS substrates.
      Closely related to the application of SERS in the analysis of trace sample and
      unknown systems, the existing cleaning methods for SERS substrates are analyzed
      and a combined chemical adsorption and electrochemical oxidation method is
      proposed to eliminate the interference of contaminants. A defocusing method is
      proposed to deal with the laser-induced sample decomposition problem frequently
      met in SERS measurement to obtain strong signals. The existing methods to
      estimate the surface enhancement factor, a criterion to characterize the SERS
      activity of a substrate, are analyzed and some guidelines are proposed to obtain
      the correct enhancement factor.

PMID- 19381619
TI  - Posterior cingulate and retrosplenial cortex connections of the caudal superior
      temporal region in the rhesus monkey.
AB  - The rostral part of the superior temporal gyrus (STG) is known to project to
      ventral temporal cortex, but analogous paralimbic connections of the caudal STG
      have received comparatively less attention. The present study of the connections
      of the STG with medial paralimbic cortex showed that the caudal part of the STG
      (area Tpt and caudal area paAlt) and adjacent cortex of the upper bank of the
      superior temporal sulcus (caudal area TPO) have reciprocal connections with the
      caudal cingulate gyrus (areas 23a, b and c), retrosplenial cortex (area 30), and
      area 31. By contrast, cortex of the rostral-to-mid STG (areas Ts2, Ts3, and the
      rostral part of area paAlt) and adjacent upper bank of the STS (mid-area TPO)
      have few, if any, such interconnections. It is suggested that this connectional
      pattern of the caudal STG is consistent with its putative role of localizing
      sounds in space as proposed in recent studies.

PMID- 19381620
TI  - Angular displacement perception modulated by force background.
AB  - We had recumbent subjects (n = 7) indicate the amplitude of imposed, passive yaw
      axis body rotations in the 0, 1, and 1.8 g background force levels generated
      during parabolic flight maneuvers. The blindfolded subject, restrained in a
      cradle, aligned a gravity-neutral pointer with the subjective vertical while in
      an initial position and then tried to keep it aligned with the same external
      direction during a body rotation, lasting less than 1.5 s about the z-axis 30
      degrees, 60 degrees, or 120 degrees in amplitude. All the rotations were above
      semicircular threshold levels for eliciting perception of angular displacement
      under terrestrial test conditions. In 1 and 1.8 g test conditions, subjects were
      able to indicate both the subjective vertical and the amplitude of the body
      rotation reasonably accurately. By contrast in 0 g, when indicating the
      subjective vertical, they aligned the pointer with the body midline and kept it
      nearly aligned with their midline during the subsequent body tilts. They also
      reported feeling supine throughout the 0 g test periods. The attenuation of
      apparent self-displacement in 0 g is discussed in terms of (1) a possible failure
      of integration of semicircular canal velocity signals, (2) a contribution of
      somatosensory pressure and contact cues, and (3) gravicentric versus body-centric
      reference frames. The significance of the findings for predicting and preventing
      motion sickness and disorientation in orbital space flight and in rotating
      artificial gravity environments is discussed.

PMID- 19381621
TI  - Multisensory warning signals: when spatial correspondence matters.
AB  - We report a study designed to investigate the effectiveness of task-irrelevant
      unimodal and bimodal audiotactile stimuli in capturing a person's spatial
      attention away from a highly perceptually demanding central rapid serial visual
      presentation (RSVP) task. In "Experiment 1", participants made speeded elevation
      discrimination responses to peripheral visual targets following the presentation
      of auditory stimuli that were either presented alone or else were paired with
      centrally presented tactile stimuli. The results showed that the unimodal
      auditory stimuli only captured spatial attention when participants were not
      performing the RSVP task, while the bimodal audiotactile stimuli did not result
      in any performance change in any of the conditions. In "Experiment 2", spatial
      auditory stimuli were either presented alone or else were paired with a tactile
      stimulus presented from the same direction. In contrast to the results of
      "Experiment 1", the bimodal audiotactile stimuli were especially effective in
      capturing participants' spatial attention from the concurrent RSVP task. These
      results therefore provide support for the claim that auditory and tactile stimuli
      should be presented from the same direction if they are to capture attention
      effectively. Implications for multisensory warning signal design are discussed.

PMID- 19381622
TI  - All-terrain vehicle use by children: a form of child neglect?

PMID- 19381623
TI  - Bare spot: a normal variant on shoulder MR arthrography.

PMID- 19381624
TI  - Peronea arteria magna.

PMID- 19381625
TI  - An isolated left subclavian artery supplied by a collateral artery from the
      abdominal aorta.
AB  - An isolated left subclavian artery is a rare anomaly. We report a 9-month-old boy
      with an isolated left subclavian artery associated with tetralogy of Fallot and
      the right aortic arch. MRI and angiography show that the blood supply through the
      left subclavian artery was maintained by a large tortuous collateral artery from
      the abdominal aorta. This type of collateral artery structure is unique.

PMID- 19381626
TI  - Duplicated Mullerian remnant in a 6-year-old boy.
AB  - We report a 6-year-old boy with large duplicated mullerian duct remnant who
      presented with recurrent urinary tract infections and dysuria. His prior
      urological problems included proximal hypospadias (repaired), urachal cyst, and a
      unilateral undescended testis. Imaging evaluation included US, MRI, and
      cystoscopy. Laparoscopic resection was performed via a retrovesical approach. The
      patient was free of symptoms after surgery.

PMID- 19381627
TI  - Protective effect of 3,5,3'-triiodothyroacetic and 3,5,3',5'-tetraiodothyroacetic
      acids on serum albumin fibrillation.
AB  - Inhibition or reversion of protein self-aggregation has been suggested as a
      possible preventive mechanism against amyloid diseases, and many efforts are
      underway to found out molecules capable to restrain the protein aggregation
      process. In this paper, the inhibitory effects of thyroid hormone analogues on
      heat-induced fibrillation process of serum albumin are reported. Among the
      analogues tested, 3,5,3',5'-tetraiodothyroacetic and 3,5,3'-triiodothyroacetic
      acid showed the most important inhibitory effects on amyloid formation. Thyroxine
      exhibits a lesser protective effect, while 3,5,3'-triiodothyronine showed no
      significant inhibition. The gaining of a negative charge together with a size
      reduction of the hormone molecule could play an essential role in the inhibition
      of fibrils formation. According to infrared spectroscopy results, the thyroid
      hormones analogues protective effects proceed via the stabilization of the
      protein native structure. The current work demonstrates the effectiveness of
      naturally occurring molecules in the inhibition of albumin fibril formation.

PMID- 19381628
TI  - MRI evaluation of anterior knee pain: predicting response to nonoperative
      treatment.
AB  - OBJECTIVE: Tibial tubercle lateral deviation and patellofemoral chondromalacia
      are associated with anterior knee pain (AKP). We hypothesized that increased
      tibial tubercle lateral deviation and patellofemoral chondromalacia on magnetic
      resonance imaging correlates with the presence of AKP and with failure of
      nonoperative management. MATERIALS AND METHODS: In this retrospective comparative
      study, a blinded musculoskeletal radiologist measured tibial tubercle lateral
      deviation relative to the trochlear groove in 15 controls, 15 physical therapy
      responders with AKP, and 15 physical therapy nonresponders with AKP. Patellar and
      trochlear cartilage was assessed for signal abnormality, irregularity, and
      defects. RESULTS: The mean tibial tubercle lateral deviation in controls,
      physical therapy responders, and physical therapy nonresponders were 9.32 +/-
      0.68, 13.01 +/- 0.82, and 16.07 +/- 1.16 mm, respectively (data are mean +/-
      standard deviation). The correlation coefficients for tubercle deviation,
      chondromalacia patellae, and trochlear chondromalacia were 0.51 (P < 0.01), 0.44
      (P < 0.01), and 0.28 (P < 0.05), respectively. On analysis of variance, tubercle
      deviation and chondromalacia patellae contributed significantly to prediction of
      AKP and response to physical therapy. The presence of chondromalacia patellae and
      a tubercle deviation greater than 14.6 mm is 100% specific and 67% sensitive with
      a positive predictive value of 100% and negative predictive value of 75% for
      failure of nonoperative management. CONCLUSION: Subjects with AKP have more
      laterally positioned tibial tubercles and are more likely to have patellar
      chondromalacia. Patients with AKP, chondromalacia patellae, and a tubercle
      deviation greater than 14.6 mm are unlikely to respond to nonoperative treatment.
      Knowledge of tibial tubercle lateralization and presence of chondromalacia
      patellae may assist clinicians in determining patient prognosis and selecting
      treatment options.

PMID- 19381629
TI  - Local expression of interferon-alpha and interferon receptors in cervical
      intraepithelial neoplasia.
AB  - PURPOSE: The present study evaluated mRNA expression of interferon-alpha (IFN
      alpha), IFN-alpha receptor subunits (IFNAR-1 and IFNAR-2) and an IFN-stimulated
      gene encoding the enzyme 2',5'-oligoadenylate synthetase (2'5'OAS) in biopsies on
      patients with varying grades of cervical intraepithelial neoplasia (CIN I, II and
      III). METHODS: Uterine cervix biopsies were collected from women with CIN I, II
      and III (n = 28) and controls without CIN lesions or human papilloma virus (HPV)
      infection (n = 17). The presence of high and low-risk HPV DNA was determined
      using hybrid capture. The mRNA levels of IFNAR-1, IFNAR-2, IFN-alpha and 2'5'OAS
      were determined by RT-PCR with specific primers. RESULTS: The control group
      exhibited a greater frequency of IFNAR-1 expression (10/17; 58.3%) than the CIN
      samples (4/28; 14.2%) (P = 0.0018), while, the expression of IFNAR-2 was also
      greater in the control samples (11/17; 64.7%) than in the patients with lesions
      (2/28; 7.1%) (P = 0.0018). Importantly, simultaneous expression of both receptors
      was observed only in the control group (8/17; 47.0%) (P = 0.0001). Among the CIN
      samples, there was one case of low expression of mRNA of IFNAR-1 and IFNAR-2. IFN
      alpha was present in 14.2% (4/28) of the CIN samples but was not expressed in the
      control group. mRNA 2'5'OAS were expressed in 28.5% (8/28) of the CIN samples and
      11.7% (2/17) of the control samples (not statistically significant). Fifty
      percent (14/28) of the CIN samples were positive for HPV DNA. CONCLUSIONS:
      Cervical biopsy samples from control women or those without neoplasia or HPV
      infection displayed higher IFN-alpha receptor expression than those with CIN,
      while simultaneous expression of both IFN-alpha receptor subunits was found only
      in the control group. There was no significant difference in mRNA expression of
      IFN-alpha and 2'5'OAS between the control and CIN groups. Then we concluded that
      the samples obtained from patients with CIN present low levels of the IFN-alpha
      receptor mRNA.

PMID- 19381630
TI  - Weekly docetaxel in patients with platinum-refractory metastatic or recurrent
      squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: The objective of the study was to investigate the efficacy and
      tolerability of weekly docetaxel in patients with platinum-refractory recurrent
      or metastatic squamous cell carcinoma of the head and neck (SCCHN). METHODS:
      Patients fulfilling the following criteria were enrolled: histologically
      confirmed SCCHN; documented progressive disease (PD) after platinum-based
      treatment; Eastern Cooperative Oncology Group (ECOG) 0-2; measurable disease; not
      candidates for local therapy. Docetaxel (35 mg/m(2)) was administered for 3
      weeks, every 4 weeks for a maximum of 6 cycles. RESULTS: A total of 23 patients
      were treated. All patients were assessable for toxicity and response. The overall
      response rate was 13.0% (3/23) and disease control rate was 34.7% (8/23). Median
      progression-free and overall survival (OS) was 9 (95% CI, 7.6-10.4 weeks) and 29
      weeks (95% CI, 10.8-47.1 weeks), respectively. Most common hematological
      toxicities were grade 1-2 anemia (6/23, 26.1%) and nonhematological toxicities
      were mild and manageable. There was no treatment-related death. CONCLUSION:
      Weekly docetaxel regimen had good clinical activity with an acceptable toxicity
      in patients with platinum-refractory SCCHN.

PMID- 19381631
TI  - Combination analyses of anti-cancer drugs on human neuroendocrine tumor cell
      lines.
AB  - PURPOSE: There is a large need for better pharmacological treatment of
      neuroendocrine tumors. The aim of this study was to investigate and quantify the
      cytotoxic potentiating effects resulting from a combination of five substances,
      NSC 95397, emetine, CGP-74514A hydrochloride, Brefeldin A and sanguinarine
      chloride, chosen from a previous screening of 1,280 pharmacologically active
      agents on neuroendocrine tumor cells, with standard cytotoxic agents currently
      used in the treatment of neuroendocrine tumors. METHOD: The human pancreatic
      carcinoid cell line BON-1, human typical bronchial carcinoid cell line NCI-H727
      and the human atypical bronchial carcinoid cell line NCI-H720 were used.
      Combinations between doxorubicin, etoposide, oxaliplatin, docetaxel, and each one
      of the five agents were studied and simultaneous exposures were explored using
      the median-effect method. RESULTS: Most of the combinations of NSC-95397 and
      emetine with doxorubicin, etoposide, docetaxel, and oxaliplatin showed synergism,
      and their remaining combinations were additive. Almost all of the CGP-74514A
      hydrochloride interactions were additive, while brefeldin A and sanguinarine
      displayed less synergy but more additive and antagonistic interactions in
      combination with the standard drugs. CONCLUSION: The synergistic and additive
      interactions make NSC-95397, emetine, and CGP-74514A hydrochloride potential
      candidates for incorporation into combination chemotherapy regimens and these
      drugs might be the suitable candidates for further clinical studies in patients
      with bronchial carcinoids and pancreatic endocrine tumors.

PMID- 19381632
TI  - Outcome of upfront combination chemotherapy followed by chemoradiation for
      locally advanced pancreatic adenocarcinoma.
AB  - PURPOSE: The role and timing of chemotherapy and radiation for treating stage III
      pancreatic adenocarcinoma remains controversial. METHODS: Treatment-naive
      patients with stage III non-resectable pancreatic adenocarcinoma were treated
      with PEFG/PEXG (cisplatin, epirubicin, 5-fluorouracil (F)/capecitabine (X),
      gemcitabine) or PDXG (docetaxel substituting epirubicin) regimen for 6 months
      followed by radiotherapy (50-60 Gy) with concurrent F or X or G. RESULTS: Ninety
      one patients were registered between April 1997 and December 2007. Forty-three
      patients (47%) had a partial remission and 38 (42%) had a stable disease.
      Thirteen patients (14%) were radically resected yielding one pathologic complete
      remission. Median survival (OS) was 16.2 months. Median progression-free survival
      was 9.9 months. Pattern of failure consisted of isolated local failure (N = 26,
      35%); both local and systemic failure (N = 14, 19%); isolated systemic failure (N
      = 35, 47%). CONCLUSION: Combination chemotherapy with four-drug regimens followed
      by chemoradiation was a feasible strategy showing relevant results in stage III
      pancreatic adenocarcinoma.

PMID- 19381633
TI  - Exact reductions of Markovian dynamics for ion channels with a single permissive
      state.
AB  - We show that the cooperative model for the kinetics of a tetrameric potassium ion
      channel derived in Nekouzadeh et al. (Biophys J 95(7):3510-3520, 2008) is an
      invariant manifold reduction of the full master equation for the channel
      kinetics. We further establish the validity of this reduction for ion channel
      models consisting of multiple independent subunits with cooperative transitions
      from a single permissive state to a conducting state. Finally, we conclude that
      solutions of the reduced model are globally asymptotically stable solutions of
      the full master equation system.

PMID- 19381634
TI  - Tumor necrosis factor receptor 1-associated periodic syndrome without fever:
      cytokine profile before and during etanercept treatment.
AB  - The objectives of this study are autoinflammatory syndromes which are usually
      characterized by repeated attacks of fever, especially in children. The
      presentation of these diseases, however, varies between entities and between
      patients of a particular syndrome. We report a 16-year-old female patient, who
      suffered from periodic erythema and myositis/fasciitis. She experienced at least
      nine attacks of dermatitis and myositis, while no fever episodes were noted over
      a 3-year period. A delay of puberty with amenorrhea and a short stature were also
      present. Laboratory investigations consistently showed markedly increased
      inflammatory parameters (especially a high serum amyloid A) and dysproteinemia.
      Because the patient's mother complained about chronic and periodic abdominal pain
      with also persistently elevated inflammatory parameters, the differential
      diagnosis included hereditary disorders resulting in chronic inflammation. The
      diagnosis of an inherited tumor necrosis factor receptor (TNFR) 1-associated
      periodic syndrome (TRAPS) was confirmed by genetic analyses. Long-term anti
      inflammatory treatment with etanercept resulted in a significant clinical
      improvement and reduction of the inflammatory parameters ESR, CRP, interleukin-6,
      TNF-alpha, and soluble TNF-alpha receptor 1, but not of interleukin-12.
      Monitoring of the cytokine profile suggested partial effectiveness of etanercept
      in the treatment of TRAPS. Hereditary fever syndromes have to be considered in
      case of chronic unexplained inflammation even if fever is no presenting symptom.

PMID- 19381635
TI  - Disease burden of psoriatic arthritis compared to rheumatoid arthritis, Hungarian
      experiment.
AB  - The objectives of this study were to assess the costs of psoriatic arthritis
      (PsA) in Hungary and to identify key cost drivers among demographic and clinical
      variables and to compare cost-of-illness of PsA and rheumatoid arthritis (RA).
      Cross-sectional retrospective survey of 183 consecutive patients from eight
      rheumatology centres was conducted. Mean direct medical, direct non medical,
      indirect and total costs were 1,876, 794, 2,904 and 5,574 euros/patient/year,
      respectively. Total costs were in significant linear relationship with health
      assessment questionnaire score and psoriatic area severity index. Costs of RA
      were higher in all domains than of PsA. Our study was the first from the Eastern
      European region that provides cost-of-illness data on PsA. Our study revealed
      that functional status and severity of skin symptoms were the key cost drivers.
      The costs of PsA in Hungary were lower than in the high-income European
      countries.

PMID- 19381636
TI  - Presenting manifestations of hemophagocytic syndrome in a male patient with
      systemic lupus erythematosus.
AB  - Hemophagocytic syndrome (HPS) is an unusual but sometimes fatal disorder. We
      reported a case of 21-year-old man who developed HPS and SLE simultaneously.
      Febrile pancytopenia, hyperferritinemia, and abnormal liver function tests were
      observed. Hemophagocytic cells were observed by means of bone marrow biopsy and
      diagnosed as HPS. The patient was treated with high-dose prednisolone, resulting
      in an excellent outcome. Early diagnosis of HPS by bone marrow biopsy is
      important for the successful treatment.

PMID- 19381637
TI  - Selected growth factors and diffusing capacity of the lung for carbon monoxide in
      patients with systemic lupus erythematosus.
AB  - The purpose of the study was to evaluate serum concentrations of selected growth
      factors and the diffusing capacity of the lung for carbon monoxide (DLCO) in 21
      females treated for systemic lupus erythematosus. The control group consisted of
      24 healthy women. Based on the high-resolution computed tomography (HRCT),
      patients were allocated to a subgroup of 11 subjects (HRCT-negative) and a
      subgroup of 10 with pulmonary abnormalities (HRCT-positive). In HRCT-negative
      patients a significantly higher level of TNF-alpha as compared with the control
      was observed and positive correlation between TNF-alpha and bFGF was revealed in
      this subgroup and in the total group of patients. DLCO was below the predicted
      value in 13 patients. No correlations between DLCO and growth factors
      concentrations were observed. DLCO reduction in asymptomatic, with respect to the
      respiratory system, SLE patients suggests a need for long-term monitoring of this
      parameter. The role of TNF-alpha in these patients requires further
      investigations.

PMID- 19381638
TI  - Pulmonary complications in human T-cell lymphotropic virus type 1 carriers with
      Sjogren's syndrome, three case reports and literature review.
AB  - In this study, we report three cases diagnosed with human T-cell lymphotropic
      virus type 1 (HTLV-1) and Sjogren's syndrome (SS) who developed pulmonary
      complications. Radiologic and pathologic findings were evaluated. Although the
      histologic diagnosis was considered to be hypersensitivity pneumonitis in case 1,
      and discordant usual interstitial pneumonia (UIP) in cases 2 and 3, lymphocytic
      alveolitis was observed in all cases. We also did a literature review and
      concluded that, although the pathologic diagnosis of pulmonary complications in
      HTLV-1 carriers with SS may vary, lymphocytic infiltrations are commonly
      observed.

PMID- 19381639
TI  - Lupus nephritis among 624 cases of systemic lupus erythematosus in Riyadh, Saudi
      Arabia.
AB  - The aim of this article is to study the prevalence, clinicolaboratory features,
      WHO histological types, therapy and renal outcome of lupus nephritis (LN) in
      Saudi Arabia. During the 27-year-period (1980-2006), 299 (47.9%) cases of LN were
      identified among the 624 cases of systemic lupus erythematosus (SLE) follow-up at
      King Khalid University Hospital, Riyadh. The female:male ratio in LN was 8.3:1,
      with a mean age of 32 years and a mean age of onset of 23 years. The WHO renal
      histological types were; Class I (1%), Class II (18.1%), Class III (10%), Class
      IV (37.1%), Class V (11.7%), and Class VI (2.7%). Azathioprine was given to 43.1%
      and pulse cyclophosphamide to 65.6% in combination with other drugs. Remission
      was seen in 226 (75.6%) patients, renal flares in 14 (4.7%), end stage renal
      disease (ESRD) in 27 (9.0%), death in 18 (6.0%), and 14 (4.7%) lost follow-up.
      The 5- and 10-year patient survival rates in our whole LN cohort by Kaplan-Meier
      analysis were 96% and 95%, respectively. The survival did not differ
      significantly in different LN classes nor did it differ significantly during the
      three periods of presentation (1980-1990, 1991-2000, and 2001-2006; P > 0.05).
      The risk factors for poor survival were found to be older age at onset (>50-years
      age; P = 0.034), ESRD (P = 0.000), and low C3 (P = 0.022). The risk factors for
      progression to ESRD were older age at onset (>50-years age; P = 0.037),
      hypertension (P = 0.009), elevated serum creatinine (P = 0.000), and
      proliferative LN (Classes III, IV; P = 0.013, P = 0.039). Different treatment
      modalities did not have significant effect on survival in the whole LN cohort (P
      = >0.05). However, pulse cyclophosphamide favored remission in Classes II, III,
      IV, and V (P = 0.023). The main causes of death were renal failure (50%) and
      infections (44.4%).

PMID- 19381640
TI  - Atypical Kawasaki disease with remarkable paucity of signs and symptoms.
AB  - We report on a 7-month-old infant with Kawasaki disease (KD) whose only
      manifestations were high-grade fever of 7 days duration, "non-toxic look" and
      "extreme irritability", thereby not meeting the criteria for the classical or the
      atypical form of the disease. The diagnosis was confirmed by the demonstration of
      a solitary aneurysm in the proximal left anterior descending coronary artery. The
      present case raises the concern that the presently laid guidelines for the
      diagnosis of atypical KD may not be adequate.

PMID- 19381641
TI  - Cloning and molecular characterization of fructose-1,6-bisphosphate aldolase gene
      regulated by high-salinity and drought in Sesuvium portulacastrum.
AB  - Sesuvium portulacastrum, a mangrove plant from seashore, is a halophyte species
      well adapted to salinity and drought. Some efforts have been made to describe its
      physiological and structural characteristics on salt and drought-tolerance, but
      the underlying molecular mechanism and key components have not yet been
      identified. Here, a fructose-1,6-bisphosphate aldolase gene, designated SpFBA,
      was isolated and characterized from S. portulacastrum roots in response to
      seawater. The SpFBA cDNA has a total length of 1452 bp with an open reading frame
      of 1071 bp, and is predicted to encode a precursor protein of 357 amino acid
      residues sharing high degree of homology with class I FBAs from other plants.
      Semi-quantitative RT-PCR analysis indicated that the SpFBA was more strongly
      expressed in roots than in leaves and stems, and the abiotic stimuli such as
      Seawater, NaCl, ABA, and PEG, could trigger a significant induction of SpFBA in
      S. portulacastrum roots within 2-12 h. Overproduction of Recombinant SpFBA
      resulted in an increased tolerance to salinity in transgenic Escherichia coli.
      All these results suggest that the SpFBA plays very important roles in responding
      to salt stress and related abiotic stimuli, and in improving the survival ability
      of S. portulacastrum under high salinity and drought.

PMID- 19381643
TI  - Magnetic resonance pancreatography: comparison of two- and three-dimensional
      sequences for assessment of intraductal papillary mucinous neoplasm of the
      pancreas.
AB  - The purpose was to compare two-dimensional (2D) magnetic resonance
      pancreatography (MRP) with 3D MRP to evaluate intraductal papillary mucinous
      neoplasm (IPMN). Thirty-four patients (22 men, 12 women; age range, 45-80 years)
      with IPMN (n = 40) were examined with MRP on 2D and 3D sequences. Two readers
      independently reviewed the images to assess the overall image quality, artifacts,
      lesion location, communication with main pancreatic duct, and potential for
      malignancy. The readers assigned their confidence level (1-5) for predicting
      ductal communication of the lesion. The results of MRP were compared with
      endoscopic retrograde pancreatography and surgical and histopathologic findings.
      Studies obtained with 3D MRP were of significantly higher technical quality than
      those obtained with 2D MRP. Although 3D MRP showed higher area under the ROC
      curve (Az) values for predicting ductal communication of the lesion, there was no
      statistical significance between Az values of 2D and 3D MRP (Az for 2D = 0.821,
      0.864 for readers 1 and 2, respectively, and Az for 3D= 0.964, 0.921). Accuracies
      for discriminating benign from malignant lesions were 70 and 67.5% (reader 1 and
      2, respectively, for 2D) and 62.5 and 80.1% (3D). 3D MRP showed superior image
      quality to that of 2D MRP but did not increase the diagnostic accuracy for
      predicting ductal communication of the lesion.

PMID- 19381644
TI  - [Temporal oscillations of retinal vessel diameter in healthy volunteers of
      different age].
AB  - PURPOSE: We investigated whether temporal oscillations of the retinal vessel
      diameter, as measured with the dynamic vessel analyzer (DVA), undergo age-related
      changes. METHODS: Vessel diameters of retinal arterial and venous segments were
      examined with the DVA in 28 medically healthy volunteers divided into two age
      groups of 14 persons each: young subjects (21-32 years) and seniors (52-70
      years). Continuous temporal records of vessel diameter were mathematically
      evaluated and divided into high-frequency (period <1.5 s) and low-frequency
      (period > or =1.5 s) oscillations. RESULTS: The phase difference between temporal
      arterial and venous vessel diameter records was higher in the young group [0.6
      (0.1, 3.3)] s [median (1st quartile, 3rd quartile)] compared with the seniors
      [0.1 (-0.4, 0.3) s]. There was a difference in the periodicity in veins between
      the groups and, in seniors, between the arteries and the veins. CONCLUSIONS: High
      frequency oscillations of vessel diameter correspond to the heartbeat. These were
      expressed more in seniors. Low-frequency oscillations were well expressed in
      young subjects. Our results show significant age-related alterations in retinal
      vessel regulation.

PMID- 19381642
TI  - Ectopic expression of a rice protein phosphatase 2C gene OsBIPP2C2 in tobacco
      improves disease resistance.
AB  - Protein phosphatase 2Cs (PP2Cs) have been demonstrated to play critical roles in
      regulation of plant growth/development, abscisic acid signaling pathway and
      adaptation to environmental stresses. Here we report the cloning and molecular
      characterization of a novel rice protein phosphatase 2C gene, OsBIPP2C2 (Oryza
      sativa L. BTH-induced protein phosphatase 2C 2). OsBIPP2C2 has three
      alternatively spliced transcripts and the largest transcript OsBIPP2C2a encodes a
      380 aa protein containing all 11 conserved catalytic subdomains of PP2Cs.
      Expression of OsBIPP2C2a was significantly induced by benzothiadiazole (BTH), one
      of defense-related signal molecules in plants. Expression of OsBIP2C2a was
      induced by infection with the blast fungus, Magnaporthe grisea, and the pathogen
      induced expression of OsBIPP2C2a in BTH-treated rice seedlings was much earlier
      and stronger than those in water-treated seedlings. Overexpression of OsBIPP2C2a
      in transgenic tobacco plants resulted in increased disease resistance against
      tobacco mosaic virus and Phytophthora parasitica var. nicotianae. Importantly,
      the OsBIPP2C2a-overexpressing transgenic tobacco plants showed constitutive
      expression of defense-related genes. These results suggest that OsBIPP2C2a may
      play an important role in disease resistance through activation of defense
      response.

PMID- 19381645
TI  - Multiple mechanisms generate the resting activity of filiform sensilla in the
      firebug (Pyrrhocoris apterus L.; Heteroptera).
AB  - The resting activity was studied in filiform sensilla of the firebug (Pyrrhocoris
      apterus). Three functional types (T(1), T(2) and T(3)) were detected on the
      abdomen. A resting discharge of nerve impulses is present in all-always in types
      T(1) and T(2) and occasionally in type T(3). In T(1) the mean rate is 57, in T(2)
      3.3 and in T(3) 0.5 imp/s. Shortening the hair length had a negligible effect on
      the resting discharge, which indicates an intrinsic origin. The resting activity
      is highly temperature dependent. In T(1), the activation energy was 56.8, in T(2)
      84 and in T(3) 61.4 kJ/mol (Q (10): 2.27, 5.6 and 5.5, respectively). Such values
      are typical for mechano-transduction, suggesting the involvement of the
      transduction mechanism itself. The destruction of the hair base in T(1) caused
      halving of the original discharge rate and shifted the discharge to a regular
      interval mode. The activation energy decreased to 38 kJ/mol. The destruction of
      the hair bases in T(2) and T(3) completely abolished the discharge. It appears
      that at least two mechanisms are involved in the generation of the resting
      activity in T(1) units while only one can be assumed in case of T(2) and T(3).

PMID- 19381647
TI  - Ventriculoperitoneal shunt dislodgement after a haircut with hair clippers in two
      shunted boys.
AB  - INTRODUCTION: Hair clippers are widely used to cut hair short at the occipital
      region for Asian school boys. A haircut as the cause of shunt dislodgement has
      not previously been reported. CASE REPORT: Two previously shunted boys presented
      with shunt dysfunction 1 to 2 days after a haircut during which hair clippers
      were used at the occipital region. Both of them have undergone shunt utilizing a
      three-piece system. During the operation, the distal catheter was found to be
      disconnected from the reservoir at the connector site in both patients. One
      patient recalled that he had felt pain and then heard a crack when the connector
      site of the reservoir was dislodged from the distal catheter at the postauricular
      region. Their ages at the time were 10 and 11 years, respectively. During the
      time period between this revision and the previous surgery, the patients
      exhibited increases in body height of 32 and 52 cm, respectively. DISCUSSION: We
      propose that when children are growing rapidly, the distal catheter is subjected
      to traction at the site of its connection with the reservoir. A haircut that
      includes the use of clippers at the occipital region causes a rapid increase in
      the shearing strain at the shunt connector site that may further stretch the
      shunt and induce shunt disconnection. Nurses and physicians must address the need
      to prevent shunt dislodgement caused by haircuts with clippers in young, rapidly
      growing, male patients who require shunts. A two- or one-piece shunt may prevent
      this complication.

PMID- 19381646
TI  - Effects of thyroid status on arginine vasotocin receptor VT2R expression and
      adrenal function in osmotically stimulated domestic fowl.
AB  - The role of thyroid hormones in the regulation of adrenal function during stress
      has been documented in mammals, but only limited reports are available in avian
      species. The present study was undertaken to analyze the effect of hyper- or
      hypothyroidism on the adrenal activity under control (hydrated) and osmotically
      stressed (water deprived, WD) conditions, with special emphasis on the expression
      of arginine vasotocin receptor VT2 (VT2R) in pituitary corticotrophs. Chickens
      were made hyper- or hypothyroidic by injecting thyroxine (T4) and 2-thiouracil
      (TU), respectively for 14 days. After 10 days of injections, one sub-group of
      both, T4- or TU-treated chickens were subjected to osmotic stress by water
      deprivation. Hyperthyroidism stimulated adrenal steroidogenic activity compared
      to euthyroid control birds, but no change was observed in the expression of VT2R.
      On the other hand, TU-induced hypothyroidism however showed no effect on adrenal
      gland, but a significant increase in the expression of VT2R was observed. Neither
      hyper- nor hypothyroidism altered pro-opiomelanocortin (POMC) mRNA levels.
      Following osmotic stress, no effect was observed either on the adrenal gland or
      on the VT2R expression in hyperthyroidic birds, but in hypothyroidic birds,
      osmotic stress stimulated adrenal steroidogenic activity and decreased VT2R
      expression in comparison to its respective controls (T4 or TU). Expression of
      POMC mRNA was again unaltered following osmotic stress. Although exact mechanism
      is not clear, the data indicate that high plasma T4 level stimulates adrenal
      activity and may also modulate function of the pituitary-adrenal axis during
      dehydration.

PMID- 19381648
TI  - Low birth weight as a risk factor for seizure following acute subdural hematoma.
AB  - PURPOSE: The purpose of this study is to determine the factors associated with
      posttraumatic seizure in patients under 2 years old with acute subdural hematoma
      (ASDH). METHODS: Twenty-one patients under 2 years old (15 males and six females)
      with ASDH, who were admitted to our hospital between January 2002 and September
      2008, were studied retrospectively. Clinical findings including birth weight and
      gestational age were defined. A head computed tomography scan was conducted at
      admission. Outcome at time of discharge was assessed using the score. RESULTS:
      Seizures occurred in eight patients (38%). Recurrent seizures occurred in three
      of eight patients (38%). In patients with seizures, birth weight, gestational
      age, and birth weight ratio were significantly lower than for those without
      seizure (p < 0.05). CONCLUSIONS: Special attention should be paid to infants with
      ASDH who have a history of low birth weight, low gestational age, and low birth
      weight ratio because risk for posttraumatic seizure is considered higher in these
      infants than in other infants.

PMID- 19381649
TI  - Early surgical management of antenatal diagnosed cystic lesions of the foramen of
      Monro causing monoventricular hydrocephalus.
AB  - INTRODUCTION: After diagnosis of an antenatal monoventricular hydrocephalus
      caused by a cystic lesion of the foramen of Monro, treatment modality and time
      frame may be difficult to assess. Previously, this type of hydrocephalus was
      often treated with internal shunting. The advent of neuroendoscopy has changed
      the surgical management of this pathology. MATERIALS AND METHODS: We report on
      two cases of cystic lesions of the foramen of Monro discovered on antenatal
      ultrasonography. A cavum veli interpositi in one case and a choroid plexus cyst
      in the other were responsible for unilateral hydrocephalus. In both cases,
      endoscopic treatment before 1 month of age was performed as the primary procedure
      with a successful outcome. CONCLUSIONS: We advise early endoscopic treatment for
      newborns presenting with progressive unilateral hydrocephalus caused by a cystic
      lesion of the foramen of Monro. It has been, in our hands, a safe and efficient
      procedure.

PMID- 19381650
TI  - Keeping CSF valve function with urokinase in children with intra-ventricular
      haemorrhage and CSF shunts.
AB  - BACKGROUND: Intra-ventricular haemorrhage (IVH) can occur spontaneously or during
      the surgical revision of ventricular cerebrospinal fluid (CSF) shunts. AIM: The
      aim of the study was to report the safety and efficacy of an original method for
      treatment of IVH that may occur at the time of valve revision aimed at
      maintaining the function of previously implanted CSF shunts. PATIENTS AND
      METHODS: We reviewed the medical records of six patients who experienced an IVH
      in the presence of a previously placed ventriculoperitoneal (VP) shunt. Five of
      the haemorrhages occurred during ventricular catheter replacement and the
      remaining one in a child given a VP shunt who sustained a spontaneous intra
      cerebral haemorrhage. We inserted an external ventricular drainage without
      removing the original shunt. Urokinase was administered via the ventricular drain
      during several days until blood clearance in the CSF. Disappearance of the
      ventricular clots was checked by a cranial computerised tomography scan, while
      CSF shunt function was verified by the children's evolution and/or by a reservoir
      tap. RESULTS: Follow-up evaluation of the six patients demonstrated that the
      existing VP shunts were functioning appropriately and that the treatment was
      safe. CONCLUSIONS: Patients with IVH complicating ventricular catheter
      replacement and patients with spontaneous bleeding who harbour a VP shunt can be
      treated by intra-ventricular urokinase to avoid the removal of the initial shunt.
      The technique has proven to be safe and utilises the ventricular drain placed for
      the acute management of the IVH. Shunt replacement will always be possible in
      case of failure of the technique we are reporting.

PMID- 19381651
TI  - Neonatal ruptured intracranial aneurysms: case report and literature review.
AB  - INTRODUCTION: Intracranial aneurysms are exceptional in neonatal patients: There
      are only 16 cases previously reported. We describe the first case of neonatal
      posterior inferior cerebellar artery (PICA) aneurysm and review the literature.
      CASE REPORT: A 7-day-old girl presented with irritability, anorexia, fever and
      abnormally enlarging head circumference. Computed tomography (CT) and magnetic
      resonance (MR) imaging demonstrated intraventricular haemorrhage, secondary
      hydrocephalus and a pontine cistern haematoma. A PICA aneurysm was suspected on
      the CT angiogram (CTA) and the diagnosis was confirmed by conventional cerebral
      angiography. She was successfully treated by surgical clipping of the parent
      vessel and excision of the aneurysm. Postoperatively, she experienced transient
      swallowing difficulties and required a ventriculo-peritoneal shunt for
      hydrocephalus. Histopathological evaluation demonstrated a calcified arterial
      wall with thrombosis, signs of prior haemorrhage and the absence of the internal
      elastic lamina. CONCLUSION: Neonatal intracranial aneurysms are rare. Clinical
      presentation of subarachnoid haemorrhage in this age group is often non-specific.
      First-line investigation should start with transfontanelle cranial ultrasound,
      followed by MR angiography then CTA if necessary. Posterior circulation aneurysms
      and large or giant aneurysms are more frequent in neonates and children than in
      adults. Early diagnosis and treatment are important for improved outcome. Surgery
      is better tolerated than in adults.

PMID- 19381652
TI  - Traumatic false aneurysm of the left gastric artery.
AB  - We present a patient with a false aneurysm of the left gastric artery, associated
      with anomalous hepatic artery anatomy, following suspected non-accidental blunt
      abdominal trauma. We postulate that the anomalous anatomy contributed to the
      pathogenesis of the lesion by restricting the mobility of the left gastric artery
      during upward movement of the liver. Trans-catheter embolization of the offending
      vessel was successful.

PMID- 19381653
TI  - Iatrogenic esophageal perforation in children.
AB  - Esophageal perforation is most commonly iatrogenic in origin with nasogastric
      tube insertion, stricture dilation, and endotracheal intubation, being the most
      frequent sources of the injury in infants and children. Clinical presentation
      depends on whether the cervical, thoracic, or abdominal esophagus is injured. Any
      patient complaining of chest pain after an upper endoscopy has esophageal
      perforation until proven otherwise. In infants and children, plain chest films
      and esophagography may assist in making the diagnosis. Hemodynamically stable
      patients with a contained perforation may be managed medically. Free perforation
      and hemodynamic lability mandates a more aggressive surgical approach for wide
      drainage of the mediastinum and pleural spaces. Exploration of the chest for
      attempted direct repair of the injury is now only rarely indicated. Mortality
      rates have been reported between 20 and 28% with delays in diagnosis and
      treatment appearing to be most strongly correlated with poor outcomes.

PMID- 19381655
TI  - Letter to the editor: reviewing reviewers and reanalysing meta-analyses of
      stapled haemorrhoidopexy?

PMID- 19381654
TI  - Genetics of the hamartomatous polyposis syndromes: a molecular review.
AB  - BACKGROUND AND AIMS: Hamartomatous polyposis syndromes are a heterogeneous group
      of disorders that are inherited in an autosomal dominant fashion. These syndromes
      only represent a small number of the inherited gastrointestinal cancer
      predisposition syndromes. However, many of these syndromes carry a substantial
      risk for developing colorectal cancer, as well as extra-colonic malignancy.
      MATERIALS AND METHODS: We searched for articles on inherited hamartomatous
      polyposis syndromes, including familial juvenile polyposis syndrome, Peutz
      Jeghers syndrome, PTEN hamartoma tumor syndrome, multiple endocrine neoplasia
      syndrome 2B, hereditary mixed polyposis syndrome, Cronkhite-Canada syndrome,
      basal cell nevus syndrome, and neurofibromatosis 1, in PubMed, Embase, and
      Elsevier ScienceDirect. In this review, we briefly discuss the diagnosis and
      clinical features of these disorders and the molecular alterations responsible
      for these syndromes. RESULTS AND CONCLUSION: Given the clinical similarities of
      these hamartomatous syndromes and the autosomal dominant pattern of inheritance,
      it is sometimes difficult to differentiate hamartomatous polyps, especially with
      atypical presentation. The molecular analysis and diagnosis make it possible to
      identify the subtype of these syndromes. In addition, these tests raise an
      intriguing possibility that surveillance and early medical intervention will
      allow for the identification of at-risk patients and the reduction of morbidity
      and mortality.

PMID- 19381656
TI  - Delayed onset of recurrent episodes of acute pseudo-obstruction in a patient with
      mitochondrial myopathy.

PMID- 19381657
TI  - Ischemic preconditioning improves stability of intestinal anastomoses in rats.
AB  - BACKGROUND: The aim of our study was to establish whether ischemic
      preconditioning (IPC) directly before performing a small bowel anastomosis has an
      effect on anastomotic stability and healing. MATERIAL AND METHODS: Forty male
      Wistar rats were randomized to five groups: control (CO, n = 8) with preparation
      of the superior mesenteric artery (SMA) but without IPC. IPC groups had different
      intervals of ischemia (occlusion of the SMA) and reperfusion: 10 min ischemia and
      20 min reperfusion (IPC10/20, n = 7), 10 min ischemia and 30 min reperfusion
      (IPC10/30, n = 8), 15 min ischemia and 20 min reperfusion (IPC15/20, n = 8), and
      15 min ischemia and 30 min reperfusion (IPC15/30, n = 9). On the fourth
      postoperative day, the animals were relaparotomized: bursting pressure,
      hydroxyproline concentration, and histological ischemia mucosal injury scale of
      the anastomosis were assessed. RESULTS: Four days after operation, the mean
      bursting pressure was 73 +/- 6 mmHg in the control group, whereas it was
      significantly higher in IPC10/20 (113 +/- 11 mmHg; p = 0.018), IPC10/30 (110 +/-
      13 mmHg; p = 0.001), and IPC15/30 (124 +/- 9 mmHg; p = 0.003). IPC15/20 did not
      show a significant difference (63 +/- 2 mmHg; p = 0.4). We did not find a
      significant effect regarding hydroxyproline concentration, but IPC diminished
      mucosal injury. CONCLUSIONS: IPC directly before performing a small bowel
      anastomosis has a time-dependent beneficial effect on anastomotic stability, thus
      indicating a new clinical approach to improve the healing process of intestinal
      anastomosis.

PMID- 19381658
TI  - Classification and basic pathology of Alzheimer disease.
AB  - The lesions of Alzheimer disease include accumulation of proteins, losses of
      neurons and synapses, and alterations related to reactive processes.
      Extracellular Abeta accumulation occurs in the parenchyma as diffuse, focal or
      stellate deposits. It may involve the vessel walls of arteries, veins and
      capillaries. The cases in which the capillary vessel walls are affected have a
      higher probability of having one or two apoepsilon 4 alleles. Parenchymal as well
      as vascular Abeta deposition follows a stepwise progression. Tau accumulation,
      probably the best histopathological correlate of the clinical symptoms, takes
      three aspects: in the cell body of the neuron as neurofibrillary tangle, in the
      dendrites as neuropil threads, and in the axons forming the senile plaque
      neuritic corona. The progression of tau pathology is stepwise and stereotyped
      from the entorhinal cortex, through the hippocampus, to the isocortex. The
      neuronal loss is heterogeneous and area-specific. Its mechanism is still
      discussed. The timing of the synaptic loss, probably linked to Abeta peptide
      itself, maybe as oligomers, is also controversial. Various clinico-pathological
      types of Alzheimer disease have been described, according to the type of the
      lesions (plaque only and tangle predominant), the type of onset (focal onset),
      the cause (genetic or sporadic) and the associated lesions (Lewy bodies, vascular
      lesions, hippocampal sclerosis, TDP-43 inclusions and argyrophilic grain
      disease).

PMID- 19381659
TI  - Calcaneal osteotomy for the treatment of plantar fasciitis.
AB  - BACKGROUND: Plantar fascia release is the main procedure for plantar fasciitis
      which does not respond to conservative treatment. However, this procedure is
      sometimes accompanied by lateral column pain due to loss of the longitudinal arch
      height after surgery. To avoid this complication, we performed calcaneal
      osteotomy. The aim of this study was to clarify the efficacy of this procedure.
      METHODS: A retrospective clinical and radiographic study was conducted for 11
      patients (11 feet) who had undergone calcaneal osteotomy for the treatment of
      intractable plantar fasciitis. Three of the patients were males and eight were
      females, with an average age of 46 (range 24-70) years. Calcaneal osteotomy was
      performed from 1 cm anterior of the calcaneal attachment of the plantar fascia to
      1 cm anterior of the calcaneal attachment of the Achilles tendon, and the
      proximal fragment was displaced approximately 5 mm in the plantar direction. The
      patients with a pronated foot before surgery underwent an additional
      approximately 5 mm medial displacement of the proximal fragment. RESULT:
      Significant improvement was seen between the American Orthopaedic Foot and Ankle
      Society Ankle-Hindfoot score before surgery and at final follow-up (P < 0.0001).
      With regard to the radiographic parameters which evaluated longitudinal arch
      height, significant improvement was seen between the talar pitch (P = 0.0002),
      calcaneal plantar angle (P < 0.0001) and lateral talocalcaneal angle (P = 0.0251)
      before and at 2 years after surgery. One patient with severe pes planus before
      surgery showed poor clinical and radiographic results. CONCLUSIONS: This
      procedure can bring about good results in patients who do not have severe pes
      planus.

PMID- 19381660
TI  - The influence of talonavicular versus double arthrodesis on load dependent motion
      of the midtarsal joint.
AB  - BACKGROUND: Today the most frequently used operative procedures in advanced
      arthritis of the hindfoot joints are isolated talonavicular arthrodesis and
      double arthrodesis (involving the talonavicular and calcaneocuboid joints, i.e.
      the Chopart joint). This in vitro study investigates whether the fusion of the
      talonavicular joint alone can provide the hindfoot, as well as a midfoot, with
      comparable biomechanical stability as the double arthrodesis does. Hence with the
      less-invasive intervention the same benefit in terms of pain reduction and better
      functionality could be achieved. METHODS: In a series of ten fresh cadaver feet
      without any radiological pathologies, we measured the range of motion of
      different tarsal bones in three planes under axial stress. Every foot was loaded
      without arthrodesis, after talonavicular and after double arthrodesis, by
      charging tibia and fibula with a force of 350 N using a calibrated Instron(r)
      load frame. Each tarsal bone was marked with a K-wire and its motion was measured
      by registering the movement of the wire's shade that was projected onto the
      surrounding walls of the trial box. RESULTS: Both operative procedures led to a
      considerable reduction of the motion of every marked bone to a mean of 18% of the
      preoperative value. In direct comparison of the two simulated arthrodeses we
      found for every bone and in every plane only minimal differences of the mean
      excursions of 1.0 mm on average. Both fusions lead to equal residual tarsal bone
      motion postoperatively, and provide the midtarsal joint as well as the subtalar
      joint with comparable biomechanical stability. CONCLUSIONS: Isolated
      talonavicular arthrodesis is a useful and effective alternative to double
      arthrodesis. It is the less complicated, less-invasive and functionally
      equivalent operative option for arthritic alterations of the hindfoot and
      transverse tarsal joint.

PMID- 19381661
TI  - The effect of ethanol intake on tendon healing: a histological and biomechanical
      study in a rat model.
AB  - INTRODUCTION: Ethanol has a suppressive effect on inflammation and the immune
      system, but the effect of ethanol on tendon healing in vivo has not been studied.
      The purpose of this study was to investigate the histological and biomechanical
      effects of ethanol intake on tendon healing in a rat tendon injury model.
      MATERIALS AND METHODS: Forty-seven rats were randomly assigned to either ethanol
      or control groups. Progressively increasing concentrations of ethanol combined
      with glucose were administered to these rats in their drinking water. After 1
      week, the Achilles tendon of each rat was injured proximal to its insertion on
      the calcaneus. All rats were euthanized at 4 weeks. The tendons were evaluated
      both histologically and biomechanically. The histologic examination of these
      tendons was done using a semi-quantitative 4-point scale to rate cell morphology,
      the degree of ground substance staining, collagen organization, and vascular
      changes. Load to failure (N) strength was obtained with biomechanical testing.
      RESULTS: Tendon failure loads were lower in the ethanol group (31.6 +/- 8.8 N)
      than in the control group (39.7 +/- 8.2 N) (P = 0.04). Histologic tenocyte scores
      were higher in the ethanol group (1.90 +/- 0.73) than the control group (0.9 +/-
      0.73) (P = 0.01). CONCLUSION: Ethanol ingestion resulted in abnormal tenocyte
      morphology, disorganized collagen bundles with a tendency toward increased
      tenocyte number, and neovascularization 3 weeks after the tendon injury
      indicating delayed and abnormal healing. The healing tendons in the alcohol
      treated group failed at statistically lower loads than the control group.

PMID- 19381662
TI  - Learning from the learning curve in total hip resurfacing: a radiographic
      analysis.
AB  - BACKGROUND: Operation of hip resurfacing prosthesis is a technically demanding
      procedure accompanied by a learning curve. To our knowledge no objective data on
      this learning curve are available in the literature. METHODS: For the first 40
      resurfacing hip prostheses implanted by a single-surgeon radiographic 'learning
      curve' analysis was performed. Optimal implant positioning on preoperative
      digital templating was compared with the eventual implant position
      postoperatively, measured by six establishes radiographic parameters and compared
      for four chronological cohorts of patients. RESULTS: A learning curve was clearly
      present and an optimal result was established in the last cohort. Pitfalls were a
      relatively steep cup position initially and a stem position in the posterior 1/3
      of the collum. Besides marginal medialization a fully anatomic reconstruction of
      the center of rotation was achieved. CONCLUSION: In total hip resurfacing one
      should recognize the presence of a learning curve. This learning curve appears to
      be acceptable and a reproducible optimal implant positioning can be achieved
      quickly.

PMID- 19381663
TI  - Prevalence of bacterial vaginosis in pregnant women and predictive value of
      clinical diagnosis.
AB  - PURPOSE: To study the prevalence of bacterial vaginosis (BV) in pregnant women
      and to evaluate the accuracy of clinical criteria for the diagnosis of BV.
      METHODS: In this observational study 502 asymptomatic pregnant women were
      screened for bacterial vaginosis in a rural health care facility by Gram stain.
      Accuracy of clinical diagnosis using individual and two of Amsel's criteria was
      evaluated. RESULTS: The frequency of BV was 8.6% by Nugent's method. For Amsel's
      criteria, sensitivity and specificity was 51.2 and 98%, with 71% PPV and 95.5%
      NPV. The most sensitive individual criterion was vaginal pH, but with lowest
      specificity. The criterion with highest specificity was clue cells. The
      combination of the two criteria, vaginal pH and positive amine test, had best
      positive and negative predictive values 60.5 and 97.8%, respectively. CONCLUSION:
      The diagnosis of BV according to Amsel's criteria may be simplified using a
      combination of the two criteria, vaginal pH and amine test, in settings where
      microscopy or Gram staining is not available.

PMID- 19381664
TI  - Adiponectin during pregnancy: correlation with fat metabolism, but not with
      carbohydrate metabolism.
AB  - BACKGROUND: Several studies show an association of adiponectin deficiency with
      obesity, insulin resistance and dysfunctional fat metabolism. This study
      investigates to what extent the correlations described occurs in pregnant women.
      METHOD: Metabolism parameters and adiponectin serum levels were measured in 32
      pregnant women at various times during their pregnancies and during the first six
      postpartum weeks. RESULTS: In this random group of pregnant subjects no
      correlation was found between adiponectin and insulin, C-peptides, blood sugar
      levels or BMI. No correlation was found between adiponectin and carbohydrate
      metabolism. The adiponectin levels of the pregnant women correlated negatively
      with triglyceride levels during the various stages of pregnancy; in the 36th week
      of gestation and at 6 weeks after the birth a positive correlation with HDL
      cholesterol was observed. The decrease in adiponectin concentration in pregnancy
      must therefore be more closely connected with changes in fat metabolism than with
      an increase in insulin resistance or weight gain during the pregnancy. The
      decrease in adiponectin does not correlate with an increase in body fat, BMI or
      weight; however, it does correlate with metabolism. The mechanisms of the
      regulation, which causes adiponectin levels to fall, is still unknown.

PMID- 19381665
TI  - Chronic myelomonocytic leukemia presenting severe uterine hemorrhage due to
      uterine infiltration of leukemic cells and early-stage endometrial
      adenocarcinoma.

PMID- 19381666
TI  - Perinatal outcomes of elderly primiparous dichorionic twin pregnancies conceived
      by in vitro fertilization compared with those conceived spontaneously.
AB  - OBJECTIVE: To examine the perinatal outcomes of elderly primiparous dichorionic
      twin pregnancies conceived by in vitro fertilization (IVF) compared with those
      conceived spontaneously. METHODS: Data were collected from primiparous women aged
      35 and older with dichorionic twin pregnancy conceived by IVF (n = 64) and those
      conceived spontaneously (n = 87). Data included antenatal data, gestational age
      at delivery, obstetric complications such as preeclampsia, gestational diabetes,
      placental previa and placental abruption, mode of delivery, birth weight, birth
      weight discordance, fetal demise, Apgar score at 1 min and umbilical areterial
      pH. RESULTS: The rate of elective Cesarean sections in the group conceived by IVF
      was significantly higher than that conceived spontaneously. There were no
      significant differences in other variables between the two groups. CONCLUSIONS:
      The current results did not support the IVF-related risks of elderly primiparous
      dichorionic twin pregnancies.

PMID- 19381667
TI  - Flare-up of genital tuberculosis following endometrial aspiration in a patient of
      generalized miliary tuberculosis.
AB  - INTRODUCTION: Genital tuberculosis is often neglected by health-care providers,
      but is an important cause of significant morbidity for the affected women. CASE
      REPORT: We report a rare case of tuberculosis (TB) flare in a 28-year-old
      nulliparous woman following endometrial aspiration (EA), which drained 30 ml pus.
      Following this, she developed high-grade fever with pain abdomen, guarding and
      rigidity. PCR was positive for mycobacterium and histopathology showed
      necrotizing granulomatous endometritis. She also showed features of genitourinary
      TB and chronic tubercular meningitis and was started on antitubercular therapy.
      CONCLUSION: To conclude, EA requires concern and a higher precision in the
      diagnosis of this insidious disease that primarily necessitates a clinical
      awareness of this serious health problem, to prevent such flare-up of TB. The
      clinician should be aware that isolation of TB requires special methods and this
      diagnosis should be considered while dealing with patients born in countries with
      high prevalence of TB.

PMID- 19381668
TI  - Clinical features of hemolysis, elevated liver enzymes, and low platelet count
      syndrome in undiagnosed Wilson disease: report of two cases.
AB  - INTRODUCTION: Wilson's disease (WD) is an autosomal recessive disorder
      characterized by toxic accumulation of copper mainly in the liver and brain. The
      hepatic manifestation of WD is diverse and may include asymptomatic elevation of
      aminotransferase, chronic hepatitis, cirrhosis, or acute/fulminant hepatic
      failure. Characteristic of acute hepatic failure in WD is concomitance of acute
      intravascular hemolytic anemia that in some patients may represent a first
      clinical symptom of WD. The diagnosis of acute Wilsonian liver failure is
      difficult, as similar signs may be observed in other clinical conditions. In
      pregnant patients with unrecognized WD, liver failure with hemolysis may be
      interpreted as the low platelet count (HELLP) syndrome. PATIENTS: We describe two
      women, who developed the clinical features of hemolysis, elevated liver enzymes,
      and HELLP syndrome. In both, further diagnostics confirmed WD. CONCLUSION: WD
      should be remembered in the differential diagnostics of HELLP syndrome.

PMID- 19381669
TI  - Prediction of fetal lung immaturity using gestational age, patient
      characteristics and fetal lung maturity tests: a probabilistic approach.
AB  - OBJECTIVES: The lecithin/sphingomyelin (L/S) ratio and the lamellar body count
      (LBC) can be used to predict respiratory distress syndrome (RDS). DESIGN: We
      performed a retrospective cohort study among consecutive women who underwent
      amniotic fluid sampling for the assessment of fetal lung maturity. Logistic
      regression was used to construct models for the prediction of RDS in three
      gestational age categories, with models based on clinical characteristics only,
      clinical characteristics and the LBC, and on clinical characteristics and L/S
      ratio. RESULTS: When amniotic fluid was collected <30 weeks, the specificity of
      the LBC was 30% and the sensitivity 100%. Addition of the L/S ratio increased the
      specifity to 60%, for a sensitivity of 100%. When amniocentesis was performed
      between 30 and 33 weeks, addition of the L/S ratio only marginally improved the
      performance of the LBC. CONCLUSIONS: At a gestational age <30 weeks, the L/S
      ratio has additional value over the LBC. Above 30 weeks of gestation, single use
      of the LBC seems sufficient.

PMID- 19381670
TI  - A cDNA microarray analysis identifies 52 genes associated with cis
      diamminedichloroplatinum susceptibility in head and neck squamous cell carcinoma
      cell lines.
AB  - We analyzed the cis-diamminedichloroplatinum (CDDP) susceptibility of ten head
      and neck squamous cell carcinoma (HNSCC) cell lines and found that this
      susceptibility varied significantly among the cell lines. Apoptotic cell death
      was predominant after the CDDP treatment, and a significant association was
      observed between the induction of apoptosis and the CDDP susceptibility. An
      analysis using a cDNA microarray consisting of 23,040 genes identified 52 genes
      that showed altered expression patterns between super-sensitive and super
      resistant cell lines after the CDDP treatments. Using these 52 genes, we
      successfully distinguished the super-resistant cell lines from others. Our
      present results give us valuable clues to better understand the
      chemosensitivities of such cells to CDDP. This will improve the clinical
      management of patients with HNSCC.

PMID- 19381671
TI  - An estimation of Canadian population exposure to cosmic rays.
AB  - The worldwide average exposure to cosmic rays contributes to about 16% of the
      annual effective dose from natural radiation sources. At ground level, doses from
      cosmic ray exposure depend strongly on altitude, and weakly on geographical
      location and solar activity. With the analytical model PARMA developed by the
      Japan Atomic Energy Agency, annual effective doses due to cosmic ray exposure at
      ground level were calculated for more than 1,500 communities across Canada which
      cover more than 85% of the Canadian population. The annual effective doses from
      cosmic ray exposure in the year 2000 during solar maximum ranged from 0.27 to
      0.72 mSv with the population-weighted national average of 0.30 mSv. For the year
      2006 during solar minimum, the doses varied between 0.30 and 0.84 mSv, and the
      population-weighted national average was 0.33 mSv. Averaged over solar activity,
      the Canadian population-weighted average annual effective dose due to cosmic ray
      exposure at ground level is estimated to be 0.31 mSv.

PMID- 19381672
TI  - Localization of Nopp140 within mammalian cells during interphase and mitosis.
AB  - We investigated distribution of the nucleolar phosphoprotein Nopp140 within
      mammalian cells, using immunofluorescence confocal microscopy and immunoelectron
      microscopy. During interphase, three-dimensional image reconstructions of
      confocal sections revealed that nucleolar labelling appeared as several tiny
      spheres organized in necklaces. Moreover, after an immunogold labelling
      procedure, gold particles were detected not only over the dense fibrillar
      component but also over the fibrillar centres of nucleoli in untreated and
      actinomycin D-treated cells. Labelling was also consistently present in Cajal
      bodies. After pulse-chase experiments with BrUTP, colocalization was more
      prominent after a 10- to 15-min chase than after a 5-min chase. During mitosis,
      confocal analysis indicated that Nopp140 organization was lost. The protein
      dispersed between and around the chromosomes in prophase. From prometaphase to
      telophase, it was also detected in numerous cytoplasmic nucleolus-derived foci.
      During telophase, it reappeared in the reforming nucleoli of daughter nuclei.
      This strongly suggests that Nopp140 could be a component implicated in the early
      steps of pre-rRNA processing.

PMID- 19381673
TI  - A cell culture system for the induction of Mallory bodies: Mallory bodies and
      aggresomes represent different types of inclusion bodies.
AB  - Mallory bodies (MBs) represent keratin-rich inclusion bodies observed in human
      alcoholic liver disease and in several chronic non-alcoholic liver diseases. The
      mechanism of their formation and their relationship to other inclusion bodies
      such as aggresomes is incompletely understood. We could induce keratin aggregates
      typical of MBs in cultured clone 9 rat hepatocytes by transgenic expression of
      wild-type and mutant aquaporin2 or alpha1-antitrypsin and under various forms of
      other cellular stress. By immunocytochemical analysis, p62 and poly-ubiquitin,
      components of classical MBs, could be demonstrated in the keratin aggregates of
      clone 9 hepatocytes. In addition, histone deacetylase 6, a microtubule-associated
      deacetylase, was identified as a novel component of the keratin aggregates. Thus,
      together with their ultrastructural appearance as randomly oriented, organelle
      free aggregates of keratin filaments, the keratin aggregates in clone 9
      hepatocytes correspond to MBs. An imbalance in keratin 8 to 18 with very low
      levels of keratin 18 appears to be the underlying cause for their formation. The
      formation of MBs was microtubule-dependent although not depending on the activity
      of histone deacetylase 6. Forskolin-induced MBs in clone 9 hepatocytes were
      reversible structures which disappeared upon drug withdrawal. The MBs were not
      related to aggresomes since overexpressed misfolded transgenic proteins were
      undetectable in the keratin aggregates and no vimentin fiber cage was detectable,
      both of which represent hallmarks of aggresomes. Thus, cultured clone 9
      hepatocytes are a useful system to study further aspects of the pathobiology of
      MBs.

PMID- 19381674
TI  - Galectin-1 induced activation of the mitochondrial apoptotic pathway: evidence
      for a connection between death-receptor and mitochondrial pathways in human
      Jurkat T lymphocytes.
AB  - Galectin-1 (gal-1) triggers T cell death by several distinct intracellular
      pathways including the activation of the death-receptor pathway. The aim of this
      study was to investigate whether gal-1 induced activation of the death-receptor
      pathway in Jurkat T lymphocytes mediates apoptosis via the mitochondrial pathway
      linked by truncated Bid (tBid). We demonstrate that gal-1 induced proteolytic
      cleavage of the death agonist Bid, a member of the Bcl-2/Bcl-xL family and a
      substrate of activated caspase-8, was inhibited by caspase-8 inhibitor II (Z-IETD
      FMK). Downstream of Bid, gal-1 stimulated mitochondrial cytochrome c release as
      well as the activation and proteolytic processing of initiator procaspase-9 were
      effectively decreased by caspase-8 inhibitor II. Blocking of gal-1 induced
      cleavage of effector procaspase-3 by caspase-8 inhibitor II as well as by caspase
      9 inhibitors I (Z-LEHD-FMK) and III (Ac-LEHD-CMK) indicates that receptor and
      mitochondrial pathways converged in procaspase-3 activation and contribute to
      proteolytic processing of effector procaspase-6 and -7. Western blot analyses and
      immunofluorescence staining revealed that exposure of Jurkat T cells to gal-1
      resulted in the cleavage of the DNA-repair enzyme poly (ADP-ribose) polymerase,
      cytoskeletal alpha-fodrin, and nuclear lamin A as substrates of activated
      caspases. Our data demonstrate that Bid provides a connection between the death
      receptor and the mitochondrial pathway of gal-1 induced apoptosis in human Jurkat
      T lymphocytes.

PMID- 19381675
TI  - Hepatoblast and mesenchymal cell-specific gene-expression in fetal rat liver and
      in cultured fetal rat liver cells.
AB  - The aim of this study was to determine whether passaged rat fetal liver cells are
      functional hepatoblasts. Hepatocyte/hepatoblast- and liver myofibroblast-gene
      expressions were studied in adult and fetal rat liver tissues as well as in
      primary and passaged cultures of isolated rat fetal liver cells at both the mRNA
      and protein level. Desmin- and Alpha-Smooth Muscle Actin (SMA)-positive cells
      were located in the walls of liver vessels, whereas Desmin-positive/SMA-negative
      cells were distributed within the liver parenchyma. Primary cultures contained
      Prox1-positive hepatoblasts, Desmin/SMA-positive myofibroblasts and only a few
      Desmin-positive/SMA-negative cells. Albumin and alpha-fetoprotein (AFP) could be
      detected in the primary cultures and to a lesser extent after the first passage.
      The number of Desmin-positive/SMA-negative cells decreased with successive
      passage, such that after the second passage, only Desmin/SMA-positive cells could
      be detected. SMA-gene-expression increased during the passages, suggesting that
      myofibroblasts become the major cell population of fetal liver cell cultures over
      time. This observation needs to be taken into account, should passaged fetal
      liver cells be used for liver cell transplantation. Moreover it contradicts the
      concept of epithelial-mesenchymal transformation and suggests rather that
      selective overgrowth of mesenchymal cells occurs in culture.

PMID- 19381676
TI  - Doxycycline accelerates renal cyst growth and fibrosis in the pcy/pcy mouse model
      of type 3 nephronophthisis, a form of recessive polycystic kidney disease.
AB  - Nephronophthisis belongs to a family of recessive cystic kidney diseases and may
      arise from mutations in multiple genes. In this report we have used a spontaneous
      mouse mutant of type 3 nephronophthisis to examine whether the doxycycline
      inducible synthesis of Timp-2, a natural inhibitor of matrix metalloproteinases,
      can influence renal cyst growth in transgenic mice. Metalloproteinases may exert
      either a negative or a positive effect on the progression of cystic kidney
      disease, and we reasoned that this may be most effectively examined by using a
      natural inhibitor. Surprisingly, already the application of doxycycline, which
      also inhibits matrix metalloproteinases, accelerated renal cyst growth and led to
      increased renal fibrosis, an additional effect of Timp-2 was not detected. The
      positive effect of doxycycline on kidney size was not due to a non-specific
      "anabolic effect" but was specific for cystic kidneys because it was not observed
      in non-cystic kidneys. When looking for potential metabolic changes we noticed
      that the urine of control animals led to an increase in the calcium response of
      LLC-PK(1) cells, whereas the urine of doxycycline-treated mice showed the
      opposite effect and even antagonized the urine of control animals. Further
      experiments demonstrated that the urine of control animals contained a heat
      labile, proteinase K-resistant substance which appears to be responsible for the
      induction of a calcium response in LLC-PK(1) cells. We conclude that doxycycline
      accelerates cyst growth possibly by the induction of a substance which lowers the
      intracellular calcium concentration. Our data also add a note of caution when
      interpreting phenotypes of animal models based upon the tet system.

PMID- 19381677
TI  - Day-to-day variability in voluntary wheel running among genetically
      differentiated lines of mice that vary in activity level.
AB  - This study examined the day-to-day variability in voluntary wheel-running
      behavior among three genetically distinct lines of young male and female mice.
      Daily wheel revolutions were recorded at an age of 6-8 weeks in 10 males and 10
      females from each of 3 lines: selectively bred line for high wheel running (Line
      8), selectively bred for high wheel-running activity and fixed for a Mendelian
      recessive allele that reduces hind-limb muscle mass by 50% (Line 3), non-selected
      control (Line 2). There were significant mean differences in revolutions/day
      among weeks (P = 0.003), but the effect size was small (10%). Significant main
      effects for wheel running were also revealed for sex and line (P < 0.001). The
      grand mean +/- SD for the coefficient of variation (CV) of intra-individual wheel
      running was 23.0 +/- 10.8%. Although a significant main effect for the CV was
      found for week, the effect size was low (7%) (age 6 weeks, 23.4 +/- 10.9%; age 7
      weeks, 25.1 +/- 13.2%; age 8 weeks, 20.1 +/- 7.8%). The overall mean CV was
      similar between females (21.4 +/- 9.8%) and males (24.4 +/- 12.0%) and among
      lines (Line 2, 23.4 +/- 9.8%; Line 3, 20.4 +/- 7.6%; and Line 8, 25.0 +/- 14.4%).
      These findings are consistent with our previous work in young humans and lend
      further support for the hypothesis that biological mechanisms influence daily
      levels of physical activity.

PMID- 19381678
TI  - Lung-to-lung circulation times during exercise in heart failure.
AB  - Circulation time (the transit time for a bolus of blood through the circulatory
      system) is a potential index of cardiac dysfunction in chronic heart failure
      (HF). In healthy subjects, circulation time falls as cardiac output (Q) rises
      during exercise, however little is known about this index in HF. In this study we
      examined the relationship between lung-to-lung circulation time (LLCT) during
      exercise in ten HF (53 +/- 14 year, resting ejection fraction = 23 +/- 8%) and
      control subjects (51 +/- 18 year). We hypothesized that HF patients would have
      slower LLCT times during exercise when compared to control subjects. Each subject
      completed two identical incremental exercise tests during which LLCT was measured
      in one test and Q measured in the other. Q was measured using the open circuit
      C(2)H(2) washin technique and circulation time measured using an inert gas
      technique. In HF patients and control subjects, LLCT decreased and Q increased
      from rest (HF:LLCT = 53.6 +/- 8.2 s, Q = 4.3 +/- 1.1 l min(-1); control: LLCT =
      55.3 +/- 10.9 s, Q = 4.5 +/- 0.5 l min(-1)) to peak exercise (HF:LLCT = 20.6 +/-
      3.9* s, Q = 8.8 +/- 2.5* l min(-1); control:LLCT = 14.9 +/- 2.4 s, Q = 16.5 +/-
      1.2 l min(-1); *P < 0.05 vs control). LLCT was significantly (P < 0.05) slower
      for the HF group when compared to the control group during submaximal exercise
      and at peak exercise. However, at a fixed Q the HF subjects had a faster LLCT. We
      hypothesize that the faster LLCT at a fixed Q for HF patients, may be the result
      of a more intensive peripheral vasoconstriction of non-active beds and a better
      redistribution of blood flow.

PMID- 19381679
TI  - Robust path integration in the entorhinal grid cell system with hippocampal feed
      back.
AB  - Animals are able to update their knowledge about their current position solely by
      integrating the speed and the direction of their movement, which is known as path
      integration. Recent discoveries suggest that grid cells in the medial entorhinal
      cortex might perform some of the essential underlying computations of path
      integration. However, a major concern over path integration is that as the
      measurement of speed and direction is inaccurate, the representation of the
      position will become increasingly unreliable. In this paper, we study how
      allothetic inputs can be used to continually correct the accumulating error in
      the path integrator system. We set up the model of a mobile agent equipped with
      the entorhinal representation of idiothetic (grid cell) and allothetic (visual
      cells) information and simulated its place learning in a virtual environment. Due
      to competitive learning, a robust hippocampal place code emerges rapidly in the
      model. At the same time, the hippocampo-entorhinal feed-back connections are
      modified via Hebbian learning in order to allow hippocampal place cells to
      influence the attractor dynamics in the entorhinal cortex. We show that the
      continuous feed-back from the integrated hippocampal place representation is able
      to stabilize the grid cell code.

PMID- 19381680
TI  - Reduced order multiport parallel and multidirectional neural associative
      memories.
AB  - This paper proposes multiport parallel and multidirectional intraconnected
      associative memories of outer product type with reduced interconnections. Some
      new reduced order memory architectures such as k-directional and k-port parallel
      memories are suggested. These architectures are, also, very suitable for
      implementation of spatio-temporal sequences and multiassociative memories. It is
      shown that in the proposed memory architectures, a substational reduction in
      interconnections is achieved if the actual length of original N-bit long vectors
      is subdivided into k sublengths. Using these sublengths, submemory matrices, T (
      s ) or W ( s ), are computed, which are then intraconnected to form k-port
      parallel or k-directional memories. The subdivisions of N-bit long vectors into k
      sublengths save ((k-1) x 100) / k % of interconnections. It is shown, by means of
      an example, that more than 80% reduction in interconnections is achieved. Minimum
      limit in bits on k as well as maximum limit on subdivisions in k is determined.
      The topologies of reduced interconnectivity developed in this paper are symmetric
      in structure and can be used to scale up to larger systems. The underlying
      principal of construction, storage and retrieval processes of such associative
      memories has been analyzed. The effect of complexity of different levels of
      reduced interconnectivity on the quality of retrieval, signal to noise ratio, and
      storage capacity has been investigated. The model possesses analogies to
      biological neural structures and digital parallel port memories commonly used in
      parallel and multiprocessing systems.

PMID- 19381681
TI  - Role of spike-frequency adaptation in shaping neuronal response to dynamic
      stimuli.
AB  - Spike-frequency adaptation is the reduction of a neuron's firing rate to a
      stimulus of constant intensity. In the locust, the Lobula Giant Movement Detector
      (LGMD) is a visual interneuron that exhibits rapid adaptation to both current
      injection and visual stimuli. Here, a reduced compartmental model of the LGMD is
      employed to explore adaptation's role in selectivity for stimuli whose intensity
      changes with time. We show that supralinearly increasing current injection
      stimuli are best at driving a high spike count in the response, while linearly
      increasing current injection stimuli (i.e., ramps) are best at attaining large
      firing rate changes in an adapting neuron. This result is extended with in vivo
      experiments showing that the LGMD's response to translating stimuli having a
      supralinear velocity profile is larger than the response to constant or linearly
      increasing velocity translation. Furthermore, we show that the LGMD's preference
      for approaching versus receding stimuli can partly be accounted for by
      adaptation. Finally, we show that the LGMD's adaptation mechanism appears well
      tuned to minimize sensitivity for the level of basal input.

PMID- 19381682
TI  - Movement curvature planning through force field internal models.
AB  - Human motion studies have focused primarily on modeling straight point-to-point
      reaching movements. However, many goal-directed reaching movements, such as
      movements directed towards oneself, are not straight but rather follow highly
      curved trajectories. These movements are particularly interesting to study since
      they are essential in our everyday life, appear early in development and are
      routinely used to assess movement deficits following brain lesions. We argue that
      curved and straight-line reaching movements are generated by a unique neural
      controller and that the observed curvature of the movement is the result of an
      active control strategy that follows the geometry of one's body, for instance to
      avoid trajectories that would hit the body or yield postures close to the joint
      limits. We present a mathematical model that accounts for such an active control
      strategy and show that the model reproduces with high accuracy the kinematic
      features of human data during unconstrained reaching movements directed toward
      the head. The model consists of a nonlinear dynamical system with a single stable
      attractor at the target. Embodiment-related task constraints are expressed as a
      force field that acts on the dynamical system. Finally, we discuss the biological
      plausibility and neural correlates of the model's parameters and suggest that
      embodiment should be considered as a main cause for movement trajectory
      curvature.

PMID- 19381683
TI  - Motor abstraction: a neuroscientific account of how action goals and intentions
      are mapped and understood.
AB  - Recent findings in cognitive neuroscience shed light on the existence of a common
      neural mechanism that could account for action and intention to understand
      abilities in humans and non-human primates. Empirical evidence on the neural
      underpinnings of action goals and on their ontogeny and phylogeny is introduced
      and discussed. It is proposed that the properties of the mirror neuron system and
      the functional mechanism describing them, embodied simulation, enabled pre
      linguistic forms of action and intention understanding. Basic aspects of social
      cognition appear to be primarily based on the motor cognition that underpins
      one's own capacity to act, here defined as motor abstraction. On the basis of
      this new account of the motor system, it is proposed that intersubjectivity is
      the best conceived of as intercorporeity.

PMID- 19381684
TI  - Transcription factors Snail, Slug, Twist, and SIP1 in spindle cell carcinoma of
      the head and neck.
AB  - Spindle cell carcinoma (SpCC) is a biphasic tumor composed of squamous cell
      carcinoma (SCC) and malignant spindle cells. There is mounting evidence that
      epithelial-mesenchymal transition (EMT) plays an important role in the
      pathogenesis of SpCC. Transcription repression has recently emerged as a
      fundamental mechanism triggering EMT in experimental models. Our aim is to
      analyze the expression of transcription repressors Snail, Slug, Twist, and SIP1
      in SpCC of the head and neck in comparison to SCC, matched for location and
      stage. Thirty cases of SpCC and 30 cases of SCC of the head and neck were
      included. Snail, Slug, Twist, and SIP1 expression was analyzed on mRNA and
      protein levels, using real-time reverse transcription-polymerase chain reaction
      (RT-PCR) and immunohistochemistry. By RT-PCR, we found upregulation of mRNA for
      transcription factors Snail, Slug, Twist, and SIP1 in SpCC when compared to SCC.
      This upregulation was statistically significant for Slug, Twist, and SIP1 but
      nonsignificant for Snail. Immunohistochemistry was performed for Snail, Slug, and
      SIP1 and demonstrated a positive reaction for Slug and SIP1 in all cases and for
      Snail in two thirds of SpCC cases. Our finding of upregulation of all four tested
      transcription factors supports the hypothesis that EMT plays an important role in
      the pathogenesis of SpCC of the head and neck.

PMID- 19381685
TI  - Melatonin prevents the development of hyperplastic urothelium induced by repeated
      doses of cyclophosphamide.
AB  - Repeated cyclophosphamide (CP) chemotherapy increases the risk of developing
      bladder cancer, which could be due to the extremely rapid proliferation of
      urothelial cells observed in hyperplastic urothelium induced by CP treatment. We
      investigated the effect of melatonin on the development of urothelial hyperplasia
      induced by repeated CP treatment. Male ICR mice were injected with CP (150 mg/kg)
      or melatonin (10 mg/kg) with CP once a week for 3, 4 and 5 weeks. Transmission
      and scanning electron microscopy, immunohistochemistry and Western blot analysis
      were used to study the ultrastructure, apoptosis, proliferation and
      differentiation of urothelial cells. Repeated doses of CP caused the development
      of hyperplastic urothelium with up to ten cell layers and increased proliferation
      and apoptotic indices regarding Ki-67 and active caspase-3 immunohistochemistry,
      respectively. Scanning electron microscopy observations, cytokeratin and
      asymmetrical unit membrane immunohistochemistry and Western blot analysis showed
      a lower differentiation state of superficial urothelial cells. Melatonin co
      treatment prevented the development of hyperplastic urothelium, statistically
      significantly decreased proliferation and apoptotic indices after four and five
      doses of CP and caused higher differentiation state of superficial urothelial
      cells.

PMID- 19381686
TI  - Association of hormone receptor status with grading, age of onset, and tumor size
      in BRCA1-associated breast cancer.
AB  - BRCA1-associated breast cancer frequently presents with estrogen-receptor
      (ERalpha) and progesterone-receptor (PR) negativity, grade 3, and early onset. In
      contrast, in BRCA1-deficient mice, ERalpha is highly expressed in early
      tumorigenesis. In a retrospective cohort study on 587 breast cancer patients with
      deleterious BRCA1 mutations, the correlation of ER, PR status, grading, age of
      onset, and tumor size was investigated. ERalpha and PR expression decreased from
      62% in ductal carcinoma in situ (DCIS) to 20% and 16% in pT3, respectively (p
      value for ER 0.025 and PR 0.035, Fisher's exact test). The percentage of grade
      1/2 tumors decreased from 44% in DCIS to 17% in pT3 (p value 0.074). Moreover,
      ER/PR positivity increased with increasing age. Our data suggest that early stage
      BRCA1-associated breast cancers are more frequently ERalpha and PR positive and
      low grade than advanced stages.

PMID- 19381687
TI  - Serum soluble Fas level determines clinical outcome of patients with diffuse
      large B-cell lymphoma treated with CHOP and R-CHOP.
AB  - INTRODUCTION: We previously reported that serum concentrations of soluble Fas
      (sFas) predict the clinical outcome of patients with diffuse large B cell
      lymphoma (DLBCL) after treatment with CHOP but without rituximab (R). Here, we
      investigated whether the role of sFas as a prognostic factor remains valid in the
      R-CHOP era. PATIENTS: We treated 132 patients with DLBCL between October 1995 and
      September 2002 (group A: without rituximab), and 75 between December 2002 and
      March 2007 (group B: with rituximab). The patients received eight cycles of CHOP
      or THP (tetrahydropyranyl-adriamycin)-COP before September 2002, and R-CHOP or R
      THP-COP after October 2002. The distribution of patients according to the
      International Prognostic Index did not significantly differ between the groups.
      RESULTS: The 5-year overall survival (OS) rates for patients with sFas levels of
      > or = 3.0 and <3.0 ng/ml in group A were 19.8 and 61.9% (P < 0.0001), whereas
      the 3-year OS rates in group B were 54.7 and 92.2% (P < 0.01), respectively.
      Multivariate analysis using the proportional hazards model revealed that sFas
      most significantly correlated with overall survival (P < 0.05). CONCLUSION: Serum
      sFas is thus a useful tool for selecting the appropriate therapeutic strategy for
      DLBCL.

PMID- 19381688
TI  - Liver transplantation outcomes in 1,078 hepatocellular carcinoma patients: a
      multi-center experience in Shanghai, China.
AB  - PURPOSE: To evaluate current selection criteria for patients undergoing liver
      transplantation (LT) in response to hepatocellular carcinoma (HCC), and to
      analyze the prognostic factors for successful transplantation. METHODS: We
      evaluated the outcome of 1,078 consecutive patients with HCC from the Shanghai
      Multi-Center Collaborative LT Group who underwent LT over a 6-year period.
      Clinicopathologic data for these patients were evaluated. The prognostic
      significance was assessed using Kaplan-Meier survival estimates and log-rank
      tests. Multivariate study with Cox's proportional hazard model was used to
      evaluate the prognosis-relative aspects. RESULTS: We determined that expansion of
      Milan criteria to include: a solitary lesion < or = 9 cm in diameter, no more
      than three lesions with the largest < or = 5 cm, a total tumor diameter < or = 9
      cm without macrovascular invasion, lymph node invasion and extrahepatic
      metastasis (referred to as the "Shanghai criteria"), resulted in overall survival
      (OS) and disease-free survival (DFS) rates that were similar to the Milan
      criteria. Multivariate analysis using the Cox proportional hazards regression
      model showed that the Child-Pugh-Turcotte classification (P = 0.010, 0.000),
      tumor differentiation (P = 0.001, 0.000), tumor size (P = 0.000, 0.000) and
      number (P = 0.014, 0.016), macrovascular invasion (P = 0.022, 0.000) and alpha
      fetoprotein (AFP) levels (P = 0.031, 0.003) were independent predictors of OS and
      DFS, while post-LT chemotherapy (OS, P = 0.000) and tumor encapsulation (DFS, P =
      0.038) were independent predictors of OS or DFS. CONCLUSION: Shanghai criteria
      expanded the current criteria while maintaining similar survival.

PMID- 19381689
TI  - Cloning and molecular characterization of tick kynurenine aminotransferase
      (HlKAT) from Haemaphysalis longicornis (Acari: Ixodidae).
AB  - A complementary DNA coding a novel kynurenine aminotransferase (KAT) molecule
      from Haemaphysalis longicornis tick embryo was cloned and characterized. The
      transcription of the HlKAT occurs at all stages during tick development as well
      as in the midgut, salivary glands, ovary, and synganglion of adult ticks, and
      protein expression levels increased during the blood-feeding course. The HlKAT
      gene without signal peptide was successfully expressed as a glutathione S
      transferase fusion protein in soluble form, which is capable of catalyzing the
      transamination of kynurenine and 3-hydroxykynurenine to kynurenic acid and
      xanthurenic acid, respectively. The purified recombinant HlKAT showed dose
      dependent inhibition effect on the growth of equine babesial parasite, Babesia
      caballi, in in vitro culture. All results suggested that a specific HlKAT is
      present in tick and HlKAT may play an important physiological role in H.
      longicornis. This is the first report of a member enzyme of tryptophan pathway in
      Chelicerata.

PMID- 19381690
TI  - Ca2+ increases the specific coenzyme Q10 content in Agrobacterium tumefaciens.
AB  - Of various metal ions (Ca2+, Cr3+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+ and Zn2+) added
      to the culture medium of Agrobacterium tumefaciens at 1 mM, only Ca2+ increased
      Coenzyme Q10 (CoQ(10)) content in cells without the inhibition of cell growth. In
      a pH-stat fed-batch culture, supplementation with 40 mM of CaCO3 increased the
      specific CoQ(10) content and oxidative stress by 22.4 and 48%, respectively.
      Also, the effect of Ca2+ on the increase of CoQ(10) content was successfully
      verified in a pilot-scale (300 L) fermentor. In this study, the increased
      oxidative stress in A. tumefaciens culture by the supplementation of Ca2+ is
      hypothesized to stimulate the increase of specific CoQ(10) content in order to
      protect the membrane against lipid peroxidation. Our results improve the
      understanding of Ca2+ effect on CoQ(10) biosynthesis in A. tumefaciens and should
      contribute to better industrial production of CoQ(10) by biological processes.

PMID- 19381691
TI  - Construction of a new, objective prognostic score for terminally ill cancer
      patients: a multicenter study.
AB  - GOALS OF WORK: The goal of this study was to develop a new, objective prognostic
      score (OPS) for terminally ill cancer patients based on an integrated model that
      includes novel objective prognostic factors. MATERIALS AND METHODS: A multicenter
      study of 209 terminally ill cancer patients from six training hospitals in Korea
      were prospectively followed until death. The Cox proportional hazard model was
      used to adjust for the influence of clinical and laboratory variables on survival
      time. The OPS was calculated from the sum of partial scores obtained from seven
      significant predictors determined by the final model. The partial score was based
      on the hazard ratio of each predictor. The accuracy of the OPS was evaluated.
      MAIN RESULTS: The overall median survival was 26 days. On the multivariate
      analysis, reduced oral intake, resting dyspnea, low performance status,
      leukocytosis, elevated bilirubin, elevated creatinine, and elevated lactate
      dehydrogenase (LDH) were identified as poor prognostic factors. The range of OPS
      was from 0.0 to 7.0. For the above cutoff point of 3.0, the 3-week prediction
      sensitivity was 74.7%, the specificity was 76.5%, and the overall accuracy was
      75.5%. CONCLUSIONS: We developed the new OPS, without clinician's survival
      estimates but including a new prognostic factor (LDH). This new instrument
      demonstrated accurate prediction of the 3-week survival. The OPS had acceptable
      accuracy in this study population (training set). Further validation is required
      on an independent population (testing set).

PMID- 19381693
TI  - Evaluation and comparison of two prognostic scores and the physicians' estimate
      of survival in terminally ill patients.
AB  - BACKGROUND: Most terminally ill patients request information about their
      remaining life span. Professionals are not generally willing to provide prognosis
      on survival, even though they are expected to be able to do so from their
      clinical experience. This study aims to find out whether the standardized
      instruments Palliative Prognostic Index (PPI) and the Palliative Prognostic Score
      (PaP-S) are appropriate, specific, and sensitive to estimate survival time in
      patients receiving inpatient palliative care in Germany. METHOD: PPI and PaP-S
      were assessed in addition to the core documentation data set of the Hospice and
      Palliative Care Evaluation for patients admitted to the palliative care units in
      Aachen, Bonn, and Cologne. Time of survival was assessed with repeated phone
      calls to the family and was defined as the difference between the day of
      completion of the instruments (excluded) and the day of death (included).
      RESULTS: Survival time was compared with physicians' estimations and prognostic
      scores in 83 patients. Whereas the estimates of the PPI and the PaP-S correlate
      highly, even higher correlations are found for the physicians' prognosis and the
      scores. Correlations between survival time and the prognostic scores or
      physicians' prognosis were lower. Physicians' estimations overestimated survival
      time on average fourfold. Estimations were more often correct for very good and
      very bad prognosis. DISCUSSION: The prognostic scores are not able to produce a
      precise reliable prognosis for the individual patient. Nevertheless, they can be
      used for ethical decision making and team discussions. Estimating survival time
      from clinical experience seems to be easier for very bad or very good prognosis
      for physicians.

PMID- 19381692
TI  - Patterns of circadian activity rhythms and their relationships with fatigue and
      anxiety/depression in women treated with breast cancer adjuvant chemotherapy.
AB  - PURPOSE: The purpose of this study was to examine patterns of circadian activity
      rhythms and their relationship with fatigue, anxiety/depression, and
      demographic/medical variables in women receiving breast cancer adjuvant therapy
      treatments (Tx) at three times within a randomized clinical trial (RCT) designed
      to improve sleep and modify fatigue. METHODS: A RCT enrolled 219 women with stage
      I-IIIA breast cancer who were randomized 2 days prior to starting chemotherapy to
      a behavioral therapy sleep intervention or healthy eating control group. All
      cases with available data (n = 190) were included in a descriptive,
      correlational, repeated measures analysis. Activity data were collected
      continuously by wrist actigraphy for 7 days at three times: the start (Tx 1),
      continuation (Tx 3), and recovery (30 days after last Tx) of chemotherapy.
      Circadian activity rhythm parameters were generated using Action4 software
      (Ambulatory Monitoring, Inc.). Measures collected simultaneously included Piper
      Fatigue Scale, Hospital Anxiety and Depression Scale, and demographic/medical
      variables. RESULTS: Circadian activity rhythm parameters at three times in both
      groups were disrupted compared to healthy adults, but similar to values of cancer
      patients. Significant changes in mesor, amplitude, peak activity, and 24 h
      autocorrelation values were found over time in both groups. The intervention
      group's amplitude and circadian quotient values were significantly more robust.
      More robust activity rhythms were associated with lower fatigue, depressive
      symptoms, body mass index, and higher performance status in both groups.
      CONCLUSIONS: Disrupted patterns of circadian activity rhythms were prevalent and
      associated with distressing fatigue and depressive symptoms during chemotherapy
      and at recovery. The intervention resulted in more robust rhythms.

PMID- 19381694
TI  - Delayed-iatrogenic injury of the thoracic aorta by an anterior spinal
      instrumentation.
AB  - We present a case of a 15-year-old girl who presented to us with an unusual low
      back pain. About 7 years ago, this patient had corrective surgery for her
      idiopathic left thoracolumbar scoliosis. Recent surgery revealed a laceration of
      the posterior wall of the thoracic aorta by an impending screw thread. This
      injury was repaired by the vascular surgeons and, subsequently, the patient had
      full recovery without any complications.

PMID- 19381695
TI  - Patient information and education with modern media: the Spine Society of Europe
      Patient Line.
AB  - The role of the patient as an active partner in health care, and not just a
      passive object of diagnostic testing and medical treatment, is widely accepted.
      Providing information to patients is considered a crucial issue and the central
      focus in patient educational activities. It is necessary to educate patients on
      the nature of the outcomes and the benefits and risks of the procedures to
      involve them in the decision-making process and enable them to achieve fully
      informed consent. Information materials must contain scientifically reliable
      information and be presented in a form that is acceptable and useful to patients.
      Given the mismatch between public beliefs and current evidence, strategies for
      changing the public perceptions are required. Traditional patient education
      programmes have to face the potential barriers of storage, access problems and
      the need to keep content materials up to date. A computer-based resource provides
      many advantages, including "just-in-time" availability and a private learning
      environment. The use of the Internet for patient information needs will continue
      to expand as Internet access becomes readily available. However, the problem is
      no longer in finding information, but in assessing the credibility and validity
      of it. Health Web sites should provide health information that is secure and
      trustworthy. The large majority of the Web sites providing information related to
      spinal disorders are of limited and poor quality. Patient Line (PL), a patient
      information section in the Web site of Eurospine, was born in 2005 to offer
      patients and the general population the accumulated expertise represented by the
      members of the society and provide up-to-date information related to spinal
      disorders. In areas where evidence is scarce, Patient Line provides a real-time
      opinion of the EuroSpine membership. The published data reflect the pragmatic and
      the common sense range of treatments offered by the Eurospine membership. The
      first chapters have been dedicated to sciatica, scoliosis, cervical pain
      syndromes, low back pain and motion preservation surgery. Since 2008, the
      information has been available in English, German, French and Spanish. The goal
      is for Patient Line to become THE European patient information Web site on spinal
      disorders, providing reliable and updated best practice and evidence-based
      information where the evidence exists.

PMID- 19381696
TI  - The Zn center of the anaerobic ribonucleotide reductase from E. coli.
AB  - Strict and facultative anaerobes depend on a class III ribonucleotide reductase
      for their growth. These enzymes are the sole cellular catalysts for de novo
      biosynthesis of the deoxyribonucleotides needed for DNA chain elongation and
      repair. In its active form, the class III ribonucleotide reductase from
      Escherichia coli contains a free radical located on the G681 residue which is
      essential for the activation of the ribonucleotide substrate toward its
      reduction. The 3D structure of the homologous enzyme from bacteriophage T4 has
      revealed the presence of a metal center bound to four conserved cysteine
      residues. In this report we identify the metal of the E. coli enzyme as Zn. We
      show that the presence of Zn in this site protects the protein from proteolysis
      and prevents the formation of disulfide bridges within it. Finally, we show with
      the fully Zn-loaded reductase that thioredoxin or small thiols are dispensable
      for the formation of the glycyl radical. However, they are necessary for
      obtaining high turnover numbers, suggesting that they intervene in radical
      transfer steps subsequent to the formation of the glycyl radical.

PMID- 19381698
TI  - How horses (Equus caballus) see the world: humans as significant "objects".
AB  - This study aimed to determine whether horses have a kind of memory of humans
      (based on previous interactions), leading to a general significance of humans
      revealed by their reactions to humans in subsequent interactions. Subjects were
      59 adult horses used to interact daily with humans. Three types of behavioural
      tests involving an unknown experimenter evaluated three possibly different
      memorized types of human-animal interactions (not work-related, using work
      related objects, unfamiliar working task). We also performed standardized
      observations of routine interactions between each horse and its familiar handler
      (caretaker). To get a broad overview of the horses' reactions to humans, we
      recorded both investigative and aggressive behaviours during the tests,
      representing respectively a "positive" and a "negative" memory of the
      relationship. Whereas correlations between tests revealed a general perception of
      humans as either positive or negative, unusual tests, i.e. that are not usually
      performed, elicited more positive reactions. Moreover, some horses reacted
      positively to a motionless person in their box, but negatively when this same
      person approached them, for example for halter fitting. Overall, aggressive
      reactions were more reliable indicators of the relationship than positive
      reactions, both between tests and between familiar and unfamiliar humans. Our
      results also show generalization of the perception of humans. These results
      support our hypothesis that perception of humans by horses may be based on
      experience, i.e. repeated interactions. Altogether, our results support the
      hypothesis that horses can form a memory of humans that impacts their reactions
      in subsequent interactions.

PMID- 19381697
TI  - Tryptophan Cu(I)-pi interaction fine-tunes the metal binding properties of the
      bacterial metallochaperone CusF.
AB  - The periplasmic metallochaperone CusF coordinates Cu(I) and Ag(I) through a
      unique site consisting of a Met(2)His motif as well as a Cu(I)-pi interaction
      between a nearby tryptophan, W44, and the metal ion. Through mutational analyses
      we investigate here the role that W44 in CusF plays in metal coordination.
      Nuclear magnetic resonance spectra show that the specificity of CusF for Cu(I)
      and Ag(I) is not altered by mutation of W44. X-ray absorption spectroscopy
      studies reveal that W44 protects the bound Cu(I) from oxidation as well as from
      adventitious ligands. Competition assays demonstrate that W44 does not
      significantly contribute to the affinity of CusF for metal, but that substitution
      of W44 by methionine, which forms a fourth Cu(I) ligand, substantially increases
      the affinity. These studies indicate that W44 is important in maintaining a
      moderate-affinity and solvent-shielded three-coordinate environment for Cu(I),
      which has implications for the function of CusF as a metallochaperone.

PMID- 19381699
TI  - Comparing black-capped (Poecile atricapillus) and mountain chickadees (Poecile
      gambeli): use of geometric and featural information in a spatial orientation
      task.
AB  - Since Cheng (Cognition 23:149-178, 1986) first proposed the "geometric module" in
      rats, a great deal of research has focused on how other species use geometric
      information and how geometric encoding may differ across species. Here, hand
      reared and wild-caught black-capped chickadees and wild-caught mountain
      chickadees searched for food hidden in one corner in a rectangular environment.
      Previous research has shown that mountain chickadees do not spontaneously encode
      geometric information when a salient feature is present near the goal location.
      Using a slightly different training and testing procedure, we found that both
      hand-reared and wild-caught black-capped chickadees encoded geometric
      information, even in the presence of a salient landmark. Some, but not all,
      mountain chickadees also encoded geometric information. Overall, our results
      suggest that use of geometric information may be a less preferred strategy for
      mountain chickadees than for either wild-caught or hand-reared black-capped
      chickadees. To our knowledge, this is the first direct interspecies comparison of
      use of geometric information in a spatial orientation task.

PMID- 19381700
TI  - CT of blunt abdominal and pelvic vascular injury.
AB  - Computed tomography (CT) has been shown to be increasingly useful in the
      evaluation of blunt trauma patients with suspected abdominopelvic vascular
      injuries. CT findings of abdominopelvic vascular insult may be broadly
      characterized as end-organ abnormalities or direct evidence of vascular injury.
      End-organ abnormalities implying an underlying vascular insult include
      identifying an area of relative hypoperfusion in solid organ injury. Direct
      evidence of a vascular injury includes identifying an irregular or thrombosed
      vessel or an area of active hemorrhage, among other findings. This review article
      aims to review and illustrate these findings of blunt abdominopelvic vascular
      trauma. Also, evolving lessons from our level I trauma center in the use of
      multiphasic imaging to further characterize sources of a vascular blush and the
      differentiation of arterial from venous sources of active hemorrhage are
      discussed.

PMID- 19381701
TI  - Extraction of the first bolus passage in dynamic susceptibility contrast
      perfusion measurements.
AB  - OBJECT: The processing of dynamic susceptibility contrast perfusion measurements
      requires an extraction of the first bolus passage of the injected contrast agent.
      State-of-the-art methods employ the fit of a gamma variate function to the
      measured data. The use of a gamma variate function is motivated by its shape
      similarity to the expected relaxation rate time-course during the first bolus
      passage. However, the quality of this result is strongly influenced by the amount
      of overlap of the first and second bolus passage. In this work we present an
      alternative, data-driven method for the extraction of the first bolus passage
      from a measured relaxation time-course. MATERIALS AND METHODS: By using prior
      knowledge of the injection function, the measured time-courses can be transformed
      to time-courses that would occur at a shorter injection duration where the two
      bolus passages have less overlap. This time-course is found by Tikhonov
      regularized deconvolution of the measured time-courses with an injection function
      that bases on the measurement protocol. A minimum search yields the cut-off point
      at which the first bolus can be extrapolated to zero. The gamma variate fit is
      performed using Powells algorithm. The proposed approach is compared to the gamma
      variate fit approach using simulations and an exemplary dataset from one healthy
      volunteer. RESULTS: The new method performs comparably stable as the gamma
      variate function fit approach in simulations. Both methods are superior to a
      simple exponential extrapolation approach. Applied to volunteer data, the new
      method performs much faster than the gamma variate fit approach. The results
      obtained from both methods correspond well. CONCLUSION: The new method offers a
      conceptual understanding of the first bolus passage and yields similar results to
      the gamma variate function fit approach but performs much faster.

PMID- 19381702
TI  - Functional categorization of the individual morphology of the scapula.
AB  - The morphologic variations of the shoulder blade have not yet been evaluated in
      clinical medicine. We observed that subjects with less standard shapes of the
      shoulder blade often suffer from musculo-skeletal shoulder syndromes with
      concurrent intrinsic impingement syndromes or, more precisely, partial-thickness
      rotator cuff tears. This experience became a basis for an experiment, in which we
      categorized individual phenotypes of the shoulder blade. A clinically useful
      finding of the presented study is a tool for predicting patients at risk for
      manifestations of impingement syndrome and also for prediction of easy or
      complicated restoration of neuromuscular stabilization of the shoulder. Lower
      functional potential of the external rotator muscles of the shoulder is in close
      relation to the individual shape of the shoulder blade, for the most part with
      the cranio-caudal dimension of the infraspinous fossa.

PMID- 19381703
TI  - Inhibition of fatty acid synthase by Orlistat accelerates gastric tumor cell
      apoptosis in culture and increases survival rates in gastric tumor bearing mice
      in vivo.
AB  - Orlistat, an anti-obesity drug, is a potent inhibitor of fatty acid synthase
      (FAS) and tumor cell viability. It can also induce apoptotic cancer cell death.
      We examined the effects of Orlistat on cultured NUGC-3 gastric cancer cells. We
      identified that inhibition of FAS via Orlistat exposure results in rapid cellular
      damage preceded by a direct but short-lived autophagic response. The Orlistat
      induced damage can be reversed through the addition of lipid containing media in
      a process that normally leads to cell death. By limiting exogenous lipid
      availability and inhibiting FAS using Orlistat, we demonstrated both a greater
      sensitivity and amplified cancer cell death by activation of apoptosis. We have
      identified "windows of opportunity" at which time apoptosis can be aborted and
      cells can be reversed from the death pathway. However, when challenged beyond the
      window of recovery, cell death becomes all but certain as the ability to be
      rescued decreases considerably. In vivo examination of Orlistat's ability to
      inhibit gastrointestinal cancer was examined using heterozygous male C57BL/6J APC
      Min mice, which spontaneously develop a fatal gastrointestinal cancer. Mice were
      fed either a high fat (11%) or low fat (1.2%) diet containing no Orlistat or 0.5
      mg Orlistat/g of chow. Orlistat treated mice fed the high fat, but not low fat
      diet, survived 7-10% longer than the untreated controls.

PMID- 19381704
TI  - Distribution of variation over populations.
AB  - Understanding the significance of the distribution of genetic or phenotypic
      variation over populations is one of the central concerns of population genetic
      and ecological research. The import of the research decisively depends on the
      measures that are applied to assess the amount of variation residing within and
      between populations. Common approaches can be classified under two perspectives:
      differentiation and apportionment. While the former focuses on differences
      (distances) in trait distribution between populations, the latter considers the
      division of the overall trait variation among populations. Particularly when
      multiple populations are studied, the apportionment perspective is usually given
      preference (via F(ST)/G(ST) indices), even though the other perspective is also
      relevant. The differences between the two perspectives as well as their joint
      conceptual basis can be exposed by referring them to the association between
      trait states and population affiliations. It is demonstrated that the two
      directions, association of population affiliation with trait state and of trait
      state with population affiliation, reflect the differentiation and the
      apportionment perspective, respectively. When combining both perspectives and
      applying the suggested measure of association, new and efficient methods of
      analysis result, as is outlined for population genetic processes. In conclusion,
      the association approach to an analysis of the distribution of trait variation
      over populations resolves problems that are frequently encountered with the
      apportionment perspective and its commonly applied measures in both population
      genetics and ecology, suggesting new and more comprehensive methods of analysis
      that include patterns of differentiation and apportionment.

PMID- 19381705
TI  - Acute and transient psychotic disorders (ICD-10 F23): a review from a European
      perspective.
AB  - The tenth revision of the International Classification of Mental and Behavioural
      Disorders (ICD-10) introduced the category F23 'Acute and transient psychotic
      disorders' (ATPD) to incorporate clinical concepts such as the French bouffee
      delirante, cycloid psychosis (Germany), and the Scandinavian reactive and
      schizophreniform psychoses. The aim of this paper is to review the literature on
      ATPD and to examine how it has been differentiated from the other categories of
      F2 group 'schizophrenia and related disorders'. Papers published between 1993 and
      2007 were found through searches in Medline, PsychInfo and Google Scholar.
      Further references were identified from book chapters and comprehensive reviews
      of the topic. ATPD is reported as being prevalent in females and as having onset
      in early-middle adulthood. Although follow-up studies suggest that its outcome is
      more favourable than other disorders in the F2 group, ATPD tends to recur and
      half of cases convert mainly into either schizophrenia or affective disorders. No
      evidence supports the view that the traditional conditions subsumed under ATPD
      all refer to this diagnostic category. The lack of defining features and poor
      prognostic validity argue against the separation of ATPD from borderland
      categories.

PMID- 19381706
TI  - Meta-analysis of initial seizure thresholds in electroconvulsive therapy.
AB  - In electroconvulsive therapy (ECT), electrical dosage is determined using 'fixed
      dose', 'age-based' dose, or empirical titration methods. Estimation of initial
      seizure threshold (IST) has been claimed to be imperative for suprathreshold
      dosing. This systematic review aimed to determine common levels of IST, to define
      cut-off values for high IST, and to summarize reported IST associated factors.
      Medline and PsycINFO were searched from 1966 to January 2008 and relevant
      references were cross-checked. Subject headings including ECT, seizure threshold,
      dosage, and dosing were used. All articles reporting on levels of IST and/or
      associated factors were included. Of 395 potentially relevant reports, 46 studies
      on 70 samples concerning 3,023 patients were selected. Nine samples (n = 306
      patients) without available standard deviation and four samples (n = 275
      patients) treated with mixed electrode placement were excluded. Meta-analysis was
      done on 30 unilaterally treated samples (n = 1,326 patients) and 27 bilaterally
      treated samples (n = 1,116 patients). In unilateral ECT, weighted mean of IST was
      68.2 milliCoulombs (mC; 95% CI 63.2-73.3 mC), and in bilateral ECT 111.6 mC (95%
      CI 103.7-119.4 mC). Calculated cut-off values for high IST were 121 mC for
      unilateral ECT and 221 mC for bilateral ECT. According to the literature, male
      gender and use of bilateral electrode placement appeared to increase IST most
      prominently. In conclusion, calculated electrical doses for 'suprathreshold'
      right unilateral ECT and for 'moderate above threshold' bilateral ECT, using
      commonly reported IST levels, were in the same though narrower ranges as provided
      in 'fixed-dose' and 'half-age' based strategies, respectively.

PMID- 19381708
TI  - What makes a difference? Understanding the role of protective factors in
      Hungarian adolescents' depressive symptomatology.
AB  - Depressive symptomatology contributes to morbidity and mortality across the life
      course. Among factors predicting adolescent depressive symptomatology, it has
      become increasingly important to identify factors that prevent or minimize it,
      i.e., protective factors. This study examines protective factors operating in
      three contextual domains (parental, school-related and individual) that hold
      promise for explicating their role in the prevention of depressive symptomatology
      among a non-clinical adolescent population in Hungary. Data from this cross
      sectional survey were gathered using self-administered questionnaires from
      adolescents (N = 881; aged between 14 and 20 years; 44.6% females) from five
      randomly selected high schools in Szeged, Hungary. Multiple regression analyses
      revealed that individual level variables (i.e., life satisfaction and optimism)
      were important predictors of adolescent depressive symptomatology. Among parental
      variables, social support from the same-sex parents lowered depressive symptoms.
      In addition, having dinner together with one's family was a significant
      protective factor for boys, whereas talking about problems with parents was
      significant for girls. In our study, school-related factors played only a limited
      role in reducing depressive symptoms; being happy with school was a protective
      factor only for boys. As a consequence, our findings draw attention to important
      gender differences in the structuring of protective factors and their role in
      reducing depressive symptoms, which will likely continue to be an important part
      of the prevention conversation.

PMID- 19381707
TI  - The effect of the COMT val(158)met polymorphism on neural correlates of semantic
      verbal fluency.
AB  - Variation in the val(158)met polymorphism of the COMT gene has been found to be
      associated with cognitive performance. In functional neuroimaging studies, this
      dysfunction has been linked to signal changes in prefrontal areas. Given the
      complex modulation and functional heterogeneity of frontal lobe systems, further
      specification of COMT gene-related phenotypes differing in prefrontally mediated
      cognitive performance are of major interest. Eighty healthy individuals (54 men,
      26 women; mean age 23.3 years) performed an overt semantic verbal fluency task
      while brain activation was measured with functional magnetic resonance imaging
      (fMRI). COMT val(158)met genotype was determined and correlated with brain
      activation measured with fMRI during the task. Although there were no differences
      in performance, brain activation in the left inferior frontal gyrus [Brodmann
      area 10] was positively correlated with the number of val alleles in the COMT
      gene. COMT val(158)met status modulates brain activation during the language
      production on a semantic level in an area related to executive functions.

PMID- 19381709
TI  - Medication adherence for children and adolescents with first-episode psychosis
      following hospitalization.
AB  - The objective of this study was to examine the predictors associated with
      adherence to atypical antipsychotic medication following discharge from hospital
      for children and adolescents with first-episode psychosis. Sixty-five children
      and adolescents, age 15.35 +/- 2.08 years, 59% boys, who had participated in a
      longitudinal cohort study examining relapse following first hospitalization for
      episode of psychosis were included in this study. All those studied were
      discharged on one of three atypical antipsychotics, risperidone, quetiapine, or
      olanzapine between January 1999 and October 2003. Time 1 data were collected
      retrospectively from medical charts using a standardized questionnaire; time 2
      data were obtained using questionnaire mailed to participants' parents a minimum
      of 2 years post-discharge, mean 3.9 +/- 1.3 years. Variables examined as
      predictors of adherence fell into broad categories of biological, social and
      treatment variables. Discharge on concurrent pharmacologic agent for affective
      symptoms in addition to atypical antipsychotic, OR = 10.5 [95% confidence
      interval (CI) = 2.06-53.19] was a strong predictor of medication adherence in
      adolescents. The results indicated that children and adolescents discharged from
      their first hospitalization following a psychotic episode may be more likely to
      stay on prescribed antipsychotic medication if they are prescribed concurrent
      medication for affective symptoms.

PMID- 19381710
TI  - Novel residues lining the CFTR chloride channel pore identified by functional
      modification of introduced cysteines.
AB  - Substituted cysteine accessibility mutagenesis (SCAM) has been used widely to
      identify pore-lining amino acid side chains in ion channel proteins. However,
      functional effects on permeation and gating can be difficult to separate, leading
      to uncertainty concerning the location of reactive cysteine side chains. We have
      combined SCAM with investigation of the charge-dependent effects of
      methanethiosulfonate (MTS) reagents on the functional permeation properties of
      cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels. We
      find that cysteines substituted for seven out of 21 continuous amino acids in the
      eleventh and twelfth transmembrane (TM) regions can be modified by external
      application of positively charged [2-(trimethylammonium)ethyl] MTS bromide
      (MTSET) and negatively charged sodium [2-sulfonatoethyl] MTS (MTSES).
      Modification of these cysteines leads to changes in the open channel current
      voltage relationship at both the macroscopic and single-channel current levels
      that reflect specific, charge-dependent effects on the rate of Cl(-) permeation
      through the channel from the external solution. This approach therefore
      identifies amino acid side chains that lie within the permeation pathway.
      Cysteine mutagenesis of pore-lining residues also affects intrapore anion binding
      and anion selectivity, giving more information regarding the roles of these
      residues. Our results demonstrate a straightforward method of screening for pore
      lining amino acids in ion channels. We suggest that TM11 contributes to the CFTR
      pore and that the extracellular loop between TMs 11 and 12 lies close to the
      outer mouth of the pore.

PMID- 19381711
TI  - Chemical and biological characterization of estrogenicity in effluents from WWTPs
      in Ria de Aveiro (NW Portugal).
AB  - Effluents from wastewater treatment plants (WWTPs) are responsible for the input
      of estrogenic contaminants into aquatic ecosystems, leading to widespread effects
      in wildlife. In the present work, levels of estrone (E1), 17alpha- and 17beta
      estradiol (E2), 17alpha-ethinylestradiol (EE2), bisphenol A (BPA), and
      nonylphenol (NP) were quantified in effluents from WWTPs located in Ria de Aveiro
      (NW Portugal), as well as in the final effluent discharged into the Atlantic
      Ocean through the S. Jacinto submarine outfall. Reference sites, located at the
      entrance of the estuarine system and at the seaside, were also included. Samples
      were collected under summer (June 2005) and winter (February 2006) conditions.
      For the summer survey samples, estrogenicity and androgenicity were evaluated
      using the yeast estrogen screen (YES) and the yeast androgen screen (YAS) assay.
      Estrone levels varied from 0.5 to 85 ng/L in the summer survey and between <LOD
      (limits of detection) and 43 ng/L in winter; estradiol levels ranged from <LOD to
      9.2 ng/L in summer and were always <LOD in the winter survey; EE2 levels were
      always <LOD for both surveys. NP concentrations ranged from 75 ng/L up to 2,350
      ng/L in summer and from 10 to 2,410 ng/L in winter; BPA levels varied from 2.8 to
      897 ng/L in summer and from 2.6 up to 316 ng/L in winter. Biological assays
      disclosed estrogenic levels at reference sites lower than the ones reported to
      pose risk for wildlife. However, the S. Jacinto outfall effluent released high
      concentrations of NP and BPA into the marine environment.

PMID- 19381713
TI  - Adipose-derived mesenchymal stem cells: past, present, and future.

PMID- 19381712
TI  - Bacterial community composition in Brazilian Anthrosols and adjacent soils
      characterized using culturing and molecular identification.
AB  - Microbial community composition was examined in two soil types, Anthrosols and
      adjacent soils, sampled from three locations in the Brazilian Amazon. The
      Anthrosols, also known as Amazonian dark earths, are highly fertile soils that
      are a legacy of pre-Columbian settlement. Both Anthrosols and adjacent soils are
      derived from the same parent material and subject to the same environmental
      conditions, including rainfall and temperature; however, the Anthrosols contain
      high levels of charcoal-like black carbon from which they derive their dark
      color. The Anthrosols typically have higher cation exchange capacity, higher pH,
      and higher phosphorus and calcium contents. We used culture media prepared from
      soil extracts to isolate bacteria unique to the two soil types and then sequenced
      their 16S rRNA genes to determine their phylogenetic placement. Higher numbers of
      culturable bacteria, by over two orders of magnitude at the deepest sampling
      depths, were counted in the Anthrosols. Sequences of bacteria isolated on soil
      extract media yielded five possible new bacterial families. Also, a higher number
      of families in the bacteria were represented by isolates from the deeper soil
      depths in the Anthrosols. Higher bacterial populations and a greater diversity of
      isolates were found in all of the Anthrosols, to a depth of up to 1 m, compared
      to adjacent soils located within 50-500 m of their associated Anthrosols.
      Compared to standard culture media, soil extract media revealed diverse soil
      microbial populations adapted to the unique biochemistry and physiological
      ecology of these Anthrosols.

PMID- 19381714
TI  - Long-term variability in bioassessments: a twenty-year study from two northern
      California streams.
AB  - Long-term variability of bioassessments has not been well evaluated. We analyzed
      a 20-year data set (1984-2003) from four sites in two northern California streams
      to examine the variability of bioassessment indices (two multivariate RIVPACS
      type O/E scores and one multimetric index of biotic integrity, IBI), as well as
      eight metrics. All sites were sampled in spring; one site was also sampled in
      summer. Variability among years was high for most metrics (coefficients of
      variation, CVs ranging from 16% to 246% in spring) but lower for indices (CVs of
      22-26% for the IBI and 21-32% for O/E scores in spring), which resulted in
      inconsistent assessments of biological condition. Variance components analysis
      showed that the time component explained variability in all metrics and indices,
      ranging from 5% to 35% of total variance explained. The site component was large
      (i.e., >40%) for some metrics (e.g., EPT richness), but nearly absent from others
      (e.g., Diptera richness). Seasonal analysis at one site showed that variability
      among seasons was small for some metrics or indices (e.g., Coleoptera richness),
      but large for others (e.g., EPT richness, O/E scores). Climatic variables did not
      show consistent trends across all metrics, although several were related to the
      El Nino Southern Oscillation Index at some sites. Bioassessments should
      incorporate temporal variability during index calibration or include climatic
      variability as predictive variables to improve accuracy and precision. In
      addition, these approaches may help managers anticipate alterations in reference
      streams caused by global climate change and high climatic variability.

PMID- 19381715
TI  - Integrating social marketing into sustainable resource management at Padre Island
      National Seashore: an attitude-based segmentation approach.
AB  - High demand for outdoor recreation and increasing diversity in outdoor recreation
      participants have imposed a great challenge on the National Park Service (NPS),
      which is tasked with the mission to provide open access for quality outdoor
      recreation and maintain the ecological integrity of the park system. In addition
      to management practices of education and restrictions, building a sense of
      natural resource stewardship among visitors may also facilitate the NPS ability
      to react to this challenge. The purpose of our study is to suggest a segmentation
      approach that is built on the social marketing framework and aimed at influencing
      visitor behaviors to support conservation. Attitude toward natural resource
      management, an indicator of natural resource stewardship, is used as the basis
      for segmenting park visitors. This segmentation approach is examined based on a
      survey of 987 visitors to the Padre Island National Seashore (PAIS) in Texas in
      2003. Results of the K-means cluster analysis identify three visitor segments:
      Conservation-Oriented, Development-Oriented, and Status Quo visitors. This
      segmentation solution is verified using respondents' socio-demographic
      backgrounds, use patterns, experience preferences, and attitudes toward a
      proposed regulation. Suggestions are provided to better target the three visitor
      segments and facilitate a sense of natural resource stewardship among them.

PMID- 19381718
TI  - Prognostic factors for survival in patients with hepatic recurrence after
      curative resection of gastric cancer.
AB  - BACKGROUND: This study was done to evaluate the prognostic factors that may
      affect the survival of patients with recurrent hepatic metastasis after curative
      resection of gastric cancer. METHODS: We reviewed the medical records of 73
      patients with recurrent hepatic metastasis after surgical treatment of gastric
      cancer from January 1995 to December 2005. Prognostic factors were classified
      into three groups: primary tumor factors, recurrent hepatic factors, and
      treatment factors. The prognostic values of these factors were assessed using
      univariate and multivariate analyses by the log-rank test in the Kaplan-Meier
      method and Cox's proportional hazard model. RESULTS: The overall median survival
      rate of the 73 study patients was 20.0 months [95% confidence interval (CI) 15.4
      24.6 months]. The median survival rate after diagnosis of recurrent hepatic
      metastasis was 5 months (95% CI 3.5-6.5 months). Univariate analysis showed that
      the favorable prognostic factors were stage I and II among the primary tumor
      factors, no extrahepatic metastasis and unilobar distribution among the recurrent
      hepatic factors, and radiofrequency ablation (RFA) +/- chemotherapy among the
      treatment factors when operative treatment had been excluded. The independent
      favorable prognostic factors revealed by the multivariate analysis were no
      extrahepatic metastasis and RFA +/- chemotherapy. The median survival rate of
      patients who had two favorable prognostic factors was 27 months (95% CI 0-66.38
      months). CONCLUSIONS: Improvement in the survival rate can be expected with RFA
      +/- chemotherapy for patients with recurrent gastric cancer in the liver without
      extrahepatic metastasis.

PMID- 19381719
TI  - Value of multidetector row CT in the assessment of longitudinal extension of
      cholangiocarcinoma: correlation between MDCT and microscopic findings.
AB  - BACKGROUND: A few authors have reported the value of multidetector row CT (MDCT)
      for evaluating the longitudinal extent of cholangiocarcinoma. They have not
      focused on CT attenuation of a tumor and actual tumor extent along the bile
      ducts. We designed the present study to analyze attenuation. METHODS: Between
      January 2003 and July 2005, 113 consecutive patients with cholangiocarcinoma
      underwent a surgical resection following MDCT. Of these MDCT studies, 73
      (perihilar cholangiocarcinoma, n = 62; middle and distal cholangiocarcinoma, n =
      11) were suitable for analysis, and the patients were enrolled in the study.
      Patients were divided according to tumor hypoattenuation and hyperattenuation on
      MDCT. Histologic differentiation, desmoplastic reaction, and vascular density
      were microscopically compared with the tumor attenuation to differentiate the
      characteristics of the attenuation. The extent of cancer along the bile duct
      diagnosed by MDCT was compared with the actual extent determined by the
      microscopic findings. RESULTS: Hyperattenuated tumor was observed in 40 patients.
      There was no difference in histologic differentiation, desmoplastic reaction, or
      vascular density between the hyperattenuated and hypoattenuated
      cholangiocarcinomas. Neither the proximal nor the distal borders between the
      normal and thickened bile duct wall could be determined in the 33 patients with
      hypoattenuated tumor; in contrast, an accurate assessment of extent of tumor was
      obtained in 76% of the proximal borders and 82% of the distal borders in the 40
      patients with hyperattenuated tumor. CONCLUSIONS: Although the cause of the
      difference between the hyperattenuated and hypoattenuated cholangiocarcinoma
      still is unclear, MDCT can be an alternative to direct cholangiography in
      selected patients with hyperattenuated cholangiocarcinoma.

PMID- 19381720
TI  - Responding to trust: surgeons' perspective on informed consent.
AB  - BACKGROUND: Every day thousands of surgeons and patients negotiate their way
      through the complex process of decision-making about operative treatments. We
      conducted a series of qualitative studies, asking patients and surgeons to
      describe their experience and beliefs about informed decision-making and consent.
      This study focuses on surgeons' views. METHODS: Open-ended interviews and focus
      group discussions were conducted with thoracic surgeons who treated esophageal
      cancer patients by esophagectomy, and general surgeons who routinely performed
      laparoscopic cholecystectomy. Their views were analyzed using a qualitative
      approach, grounded in the perspectives of the participants. RESULTS: Five
      dominant themes emerged from the analysis: (1) making informed decisions; (2)
      communicating information and confidence; (3) managing expectations and fears;
      (4) consent as a decision to trust; (5) commitment inspired by trust. These
      themes are illustrated by verbatim quotes from the surgeon interviews.
      CONCLUSIONS: Surgeons carefully assess the risks and benefits of treatment before
      consenting to perform operative interventions. They are influenced by objective
      findings and by affective factors such as courage and the determination to
      survive expressed by their patients. They manage risks, doubts, and fears-both
      their patients' and their own-relying on trust and commitment on both sides to
      ensure the success of the surgical mission. The trust of their patients has a
      strong influence on the surgeons' decisions and actions.

PMID- 19381722
TI  - Toll-like receptor 2 gene polymorphisms Arg677Trp and Arg753Gln in chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a leading cause of death
      worldwide, with a continually rising mortality rate. As COPD is driven by
      abnormal pulmonary and systemic inflammation, Toll-like receptors (TLRs) seem to
      be important. TLRs play a key role in innate response, and in particular TLR2
      gene polymorphisms Arg677Trp and Arg753Gln have been linked to an increased risk
      of infection. The purpose of this study was to investigate whether there is a
      link between polymorphisms in TLR2 and the onset or course of COPD. We analyzed
      149 Caucasian COPD patients and 150 healthy individuals by using polymerase chain
      reaction (PCR) followed by restriction fragment length polymorphism (RFLP)
      analysis. To further characterize the disease, patients were classified according
      to GOLD and divided into two subgroups comprising a stable (60/149) course and an
      unstable (89/149) course. The TLR2 Arg677Trp mutant allele was not found in any
      of the subjects. With a prevalence of 8.72% (13/149) for TLR2 Arg753Gln, the
      patients did not differ from the controls, with a prevalence of 10.67% (16/150).
      No significant difference was apparent (P = 0.571). None of the individuals
      showed homozygosity for TLR2 Arg753Gln. With regard to the course of COPD, the
      prevalence of TLR2 Arg753Gln in the control group did not differ significantly
      either from the stable subgroup (P = 0.196) or from the unstable subgroup (P =
      0.891). Our results suggest that there is no association of the TLR2
      polymorphisms Arg677Trp and Arg753Gln with either the onset or the course of
      COPD.

PMID- 19381723
TI  - Density-dependent phytotoxicity of impatiens pallida plants exposed to extracts
      of Alliaria petiolata.
AB  - Invasive plants are by definition excellent competitors, either indirectly
      through competition for resources or directly through allelopathic inhibition of
      neighboring plants. Although both forms of competition are commonly studied,
      attempts to explore the interactions between direct and indirect competition are
      rare. We monitored the effects of several doses of extracts of Alliaria
      petiolata, a Eurasian invader in North America, on the growth of Impatiens
      pallida, a North American native, at several planting densities. The density
      dependent phytotoxicity model predicts that as plant density increases,
      individual plant size will decrease, unless a toxin is present in the soil. In
      this case, individual plant size is predicted to increase as plant density
      increases, as plants share a limited toxin dose. We tested this model using
      fractions of an A. petiolata extract enriched in flavonoids or glucosinolates, as
      well as a combined fraction. The flavonoid-enriched fraction and the combined
      fraction suppressed I. pallida growth but only when applied at a dose eight times
      higher than that expected in the field. When treated with a dose equivalent to
      estimated field exposure levels, I. pallida growth was not distinguishable from
      that of control plants that received no extract, showing that indirect
      competition for resources was more important for determining the growth of I.
      pallida than direct allelopathic inhibition by A. petiolata. This is an important
      reminder that, even though many plants have the demonstrated potential to exert
      strong allelopathic effects, those effects may not always be apparent when other
      forms of competition are considered as well.

PMID- 19381724
TI  - Predictors of completion axillary lymph node dissection in patients with positive
      sentinel lymph nodes.
AB  - BACKGROUND: Completion axillary lymph node dissection (CALND) is routinely
      performed in breast cancer patients with positive sentinel lymph nodes (SLN). We
      sought to determine the sociodemographic, pathologic, and therapeutic variables
      that were associated with CALND. METHODS: From 7/1997 to 7/2003, 1,470 patients
      with invasive breast cancer were SLN positive by intraoperative frozen section or
      final pathologic exam by hematoxylin-eosin and/or immunohistochemistry (IHC). A
      comorbidity score was assigned using Adult Comorbidity Evaluation-27 system.
      Fisher's exact, Wilcoxon tests, and multivariate logistic regression analysis
      were used. RESULTS: CALND was performed less often in patients with age >or= 70
      years compared with age < 70 years, moderate or severe comorbidities compared
      with no or mild, IHC-only positive SLN and breast conservation therapy (BCT
      compared with mastectomy. Patients who did not undergo CALND were less likely
      than CALND patients to have grade III disease, lymphovascular invasion multifocal
      disease, tumor size > 2 cm or to receive adjuvant chemotherapy. However, they
      were more likely to undergo axillary radiotherapy (RT). On multivariate analysis,
      age >or= 70 years [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.26-0.63],
      IHC-only positive SLN (OR 0.13, 95%CI 0.09-0.19), presence of moderate to severe
      comorbidities (OR 0.64, 95%CI 0.41-0.99), tumor size <or= 2 cm (OR 0.44, 95%CI
      0.29-0.66), axillary RT (OR 0.39, 95%CI 0.20-0.78), and BCT (OR 0.54, 95%CI 0.37
      0.79) were all independently associated with lower odds of CALND. CONCLUSIONS:
      The decision to perform CALND following positive SLN biopsy was multifactorial.
      Patient factors were a primary determinant for the use of CALND in our study. The
      decreased use of CALND in the BCT patients probably reflects reliance on the
      radiotherapy tangents to maintain local control in the axilla.

PMID- 19381726
TI  - The validity, reliability, responsiveness, and bias of the Manchester-Modified
      Disability of the Arm, Shoulder, and Hand score in hand injuries.
AB  - The Manchester-Modified Disability of Arm, Shoulder and Hand questionnaire (M(2)
      DASH) was developed by the authors as a modification to the original DASH
      questionnaire. In this study, we assessed the validity, reliability,
      responsiveness, and bias of the M(2) DASH questionnaire for hand injuries using
      completed M(2) DASH, Patient Evaluation Measure, and Michigan Hand Outcome
      questionnaires from 40 patients. The M(2) DASH scores showed significant positive
      correlations with the Patient Evaluation Measure and Michigan Hand Outcome scores
      suggesting validity. There was also no evidence of a statistical difference in
      the M(2) DASH scores when the condition had stabilized suggesting good test
      retest reproducibility and reliability. The effect size and the standardized
      response mean for the M(2) DASH score were greater than those for the Patient
      Evaluation Measure and Michigan Hand Outcome scores establishing that the M(2)
      DASH is highly responsive. There was no gender, hand dominance, or dominant side
      injured bias for the M(2) DASH score. There was, however, a relatively weak
      association between age and the M(2) DASH score at presentation. We conclude that
      the M(2) DASH questionnaire is a robust region-specific outcome measure. It is a
      valid and responsive questionnaire with test-retest reliability proven for hand
      injuries in this study. Gender, handedness, and side injured did not cause bias
      in the responses.

PMID- 19381727
TI  - Vascularized nerve grafts and vascularized fascia for upper extremity nerve
      reconstruction.
AB  - Since 1976, experimental and clinical studies have suggested the superiority of
      vascularized nerve grafts. In this study, a 27-year experience of the senior
      author is presented regarding vascularized nerve grafts and fascia for complex
      upper extremity nerve reconstruction. The factors influencing outcomes as well as
      a comparison with conventional nerve grafts is presented. Since 1981, 21
      vascularized nerve grafts, other than vascularized ulnar nerve, were used for
      reconstruction of nerve injuries in the upper extremity. Indications were
      prolonged denervation time, failure of the previously used conventional nerve
      grafts, and excessive scar in the recipient site. Injury was in the hand/wrist
      area (n = 5), in the forearm (n = 4), in the elbow (n = 2), in the arm (n = 4),
      or in the plexus (n = 6). Vascularized sural (n = 9), saphenous (n = 8),
      superficial radial (n = 3), and peroneal (superficial and deep) nerves were used.
      The mean follow-up was 31.4 months. Vascularized nerve grafts for upper extremity
      injuries provided good to excellent sensory return in severely scarred upper
      extremities in patients in whom conventional nerve grafts had failed. They have
      also provided relief of causalgia after painful neuroma resection and motor
      function recovery in selective cases even for above the elbow injuries. Small
      diameter vascularized nerve grafts should be considered for bridging long nerve
      gaps in regions of excessive scar or for reconstructions where conventional nerve
      grafts have failed.

PMID- 19381725
TI  - Interpreting CFSE obtained division histories of B cells in vitro with Smith
      Martin and cyton type models.
AB  - The fluorescent dye carboxyfluorescin diacetate succinimidyl ester (CFSE)
      classifies proliferating cell populations into groups according to the number of
      divisions each cell has undergone (i.e., its division class). The pulse labeling
      of cells with radioactive thymidine provides a means to determine the
      distribution of times of entry into the first cell division. We derive in
      analytic form the number of cells in each division class as a function of time
      using the cyton approach that utilizes independent stochastic distributions for
      the time to divide and the time to die. We confirm that our analytic form for the
      number of cells in each division class is consistent with the numerical solution
      of a set of delay differential equations representing the generalized Smith
      Martin model with cell death rates depending on the division class. Choosing the
      distribution of time to the first division to fit thymidine labeling data for B
      cells stimulated in vitro with lipopolysaccharide (LPS) and either with or
      without interleukin-4 (IL-4), we fit CFSE data to determine the dependence of B
      cell kinetic parameters on the presence of IL-4. We find when IL-4 is present, a
      greater proportion of cells are recruited into division with a longer average
      time to first division. The most profound effect of the presence of IL-4 was
      decreased death rates for smaller division classes, which supports a role of IL-4
      in the protection of B cells from apoptosis.

PMID- 19381728
TI  - Filling the gap: the importance of Medicaid continuity for former inmates.
AB  - Despite no federal law mandating Medicaid termination for prisoners, 90 percent
      of states have implemented policies that withdraw inmates' enrollment upon
      incarceration. This leaves a medically and psychiatrically vulnerable population
      uninsured during the months following release, a time period during which former
      inmates have been shown to have an increased risk of medical problems and death.
      We believe it is of critical importance for the 10 million Americans who cycle in
      and out of corrections each year, as well as the communities they return to, that
      Medicaid be suspended rather than terminated during incarceration.

PMID- 19381729
TI  - Teaching medicine to non-English speaking background learners in a foreign
      country.
AB  - Teaching abroad exposes medical educators to unfamiliar teaching methods and
      learning styles that can enhance their overall teaching repertoire. Based on the
      author's experience teaching residents for one month at a community hospital in
      Japan and a review of the non-English speaking background (NESB) educational
      literature, pedagogical principles and lessons for successful international NESB
      instruction are outlined. These methods include understanding the dissimilar
      linguistic, cultural, and academic backgrounds of the learners, emphasizing pace
      and clarity of speech, presenting a conceptual framework instead of detailed
      discourse on subjects, and regular visual reinforcement of spoken words. The
      limitations introduced by the language barrier and the use of interpreters are
      briefly discussed. As society and institutions of higher learning become more
      global and multicultural, clinician-educators may benefit from teaching in other
      countries in order to enhance their teaching skills with NESB learners, both
      abroad and in their own institutions.

PMID- 19381730
TI  - Dual use of veterans health administration and Indian Health Service: healthcare
      provider and patient perspectives.
AB  - BACKGROUND: Many American Indian and Alaska Native veterans are eligible for
      healthcare from Veterans Health Administration (VHA) and from Indian Health
      Service (IHS). These organizations executed a Memorandum of Understanding in 2003
      to share resources, but little was known about how they collaborated to deliver
      healthcare. OBJECTIVE: To describe dual use from the stakeholders' perspectives,
      including incentives that encourage cross-use, which organization's primary care
      is "primary," and the potential problems and opportunities for care coordination
      across VHA and IHS. PARTICIPANTS: VHA healthcare staff, IHS healthcare staff and
      American Indian and Alaska Native veterans. APPROACH: Focus groups were conducted
      using a semi-structured guide. A software-assisted text analysis was performed
      using grounded theory to develop analytic categories. MAIN RESULTS: Dual use was
      driven by variation in institutional resources, leading patients to actively
      manage health-seeking behaviors and IHS providers to make ad hoc recommendations
      for veterans to seek care at VHA. IHS was the "primary" primary care for dual
      users. There was little coordination between VHA and IHS resulting in delays and
      treatment conflicts, but all stakeholder groups welcomed future collaboration.
      CONCLUSIONS: Fostering closer alignment between VHA and IHS would reduce care
      fragmentation and improve accountability for patient care.

PMID- 19381731
TI  - The policy debate over public investment in comparative effectiveness research.
AB  - BACKGROUND: Policy makers across the political spectrum, as well as many
      clinicians and physician professional associations, have proposed that better
      information on comparative clinical effectiveness should be a key element of any
      solution to the US health-care cost crisis. This superficial consensus hides
      intense disagreements over critical issues essential to any new public effort to
      promote more comparative effectiveness research (CER). METHODS AND RESULTS: This
      article reviews the background for these disputes, summarizes the different
      perspectives represented by policy makers and advocates, and offers a framework
      to aid both practicing and academic internists in understanding the key elements
      of the emerging debate. Regarding the fundamental question of "what is CER,"
      disagreements rage over whether value or cost effectiveness should be a
      consideration, and how specific patient perspectives should be reflected in the
      development and the use of such research. The question of how to pay for CER
      invokes controversies over the role of the market in producing such information
      and the private (e.g., insurers and employers) versus public responsibility for
      its production. The financing debate further highlights the high stakes of
      comparative effectiveness research, and the risks of stakeholder interests
      subverting any public process. Accordingly there are a range of proposals for the
      federal government's role in prioritization, development, and dissemination of
      CER. CONCLUSION: The internal medicine community, with its long history of
      commitment to scientific medical practice and its leadership in evidence-based
      medicine, should have a strong interest and play an active role in this debate.

PMID- 19381733
TI  - Pancreaticojejunostomy with application of fibrinogen/thrombin-coated collagen
      patch (TachoSil) in Roux-en-Y reconstruction after pancreaticoduodenectomy.

PMID- 19381734
TI  - Inflammatory pseudotumor of the esophagus--GI image.

PMID- 19381735
TI  - Probiotics improve outcomes after Roux-en-Y gastric bypass surgery: a prospective
      randomized trial.
AB  - INTRODUCTION: Roux-en-Y gastric bypass (RNYGB) surgery offers an effective and
      enduring treatment for morbid obesity. Gastric bypass may alter gastrointestinal
      (GI) flora possibly resulting in bacterial overgrowth and dysmotility. Our
      hypothesis was that daily use of probiotics would improve GI outcomes after
      RNYGB. METHODS: Forty-four patients undergoing RNYGB were randomized to either a
      probiotic or control group; 2.4 billion colonies of Lactobacillus were
      administered daily postoperatively to the probiotic group. The outcomes of H(2)
      levels indicative of bacterial overgrowth, GI-related quality of life (GIQoL),
      serologies, and weight loss were measured preoperatively and at 3 and 6 months
      postoperatively. Categorical variables were analyzed by chi(2) test and
      continuous variables were analyzed by t test with a p < 0.05 for significance.
      RESULTS: At 6 months, a statistically significant reduction in bacterial
      overgrowth was achieved in the probiotic group with a preoperative to
      postoperative change of sum H(2) part per million (probiotics = -32.13, controls
      = 0.80). Surprisingly, the probiotic group attained significantly greater percent
      excess weight loss than that of control group at 6 weeks (controls = 25.5%,
      probiotic = 29.9%) and 3 months (38.55%, 47.68%). This trend also continued but
      was not significant at 6 months (60.78%, 67.15%). The probiotic group had
      significantly higher postoperative vitamin B12 levels than the control group.
      Both probiotic and control groups significantly improved their GIQoL. CONCLUSION:
      In this novel study, probiotic administration improves bacterial overgrowth,
      vitamin B12 availability, and weight loss after RNYGB. These data may provide
      further evidence that altering the GI microbiota can influence weight loss.

PMID- 19381737
TI  - Nonsurgical treatment of staple line leaks after laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is gaining popularity as a "per
      se" bariatric procedure due to its effectiveness on weight loss and comorbidity
      resolution. The most feared and life-threatening complication after LSG is the
      staple line leak and its management is still a debated issue. Aim of this paper
      is to analyze the incidence of leak and the treatment solutions adopted in a
      consecutive series of 200 LSG. METHODS: From October 2002 to November 2008, 200
      patients underwent LSG. Nineteen patients (9.5%) had a body mass index (BMI) of
      >60 kg/m(2). A 48-Fr bougie is used to obtain an 80-120-ml gastric pouch. An
      oversewing running suture to reinforce the staple line was performed in the last
      100 cases. The technique adopted to reinforce the staple line is a running suture
      taken through and through the complete stomach wall. RESULTS: Staple line leaks
      occurred in six patients (mean BMI 52.5; mean age 41.6 years). Leak presentation
      was early in three cases (first, second, and third postoperative (PO) day), late
      in the remaining three cases (11th, 22nd, and 30th PO day). The most common leak
      location was at the esophagogastric junction (five cases). Mortality was nihil.
      Nonoperative management (total parenteral nutrition, proton pump inhibitor, and
      antibiotics) was adopted in all cases. Percutaneous abdominal drainage was placed
      in five patients. In one case, a small fistula was successfully treated by
      endoscopic injection of fibrin glue only. Self-expandable covered stent was used
      in three cases. Complete healing of leaks was obtained in all patients (mean
      healing time 71 days). CONCLUSION: Nonoperative treatment (percutaneous drainage,
      endoscopy, stent) is feasible, safe, and effective for staple line leaks in
      patients undergoing LSG; furthermore, it may avoid more mutilating procedures
      such as total gastrectomy.

PMID- 19381736
TI  - CT scans and acute appendicitis: a five-year analysis from a rural teaching
      hospital.
AB  - INTRODUCTION: Studies examining the relationship between computed tomography (CT)
      scans and appendiceal perforation have largely been conducted in urban centers.
      The present study sought to evaluate this relationship in a rural hospital.
      METHODS AND PROCEDURES: This is a retrospective analysis of 445 patients who
      underwent appendectomies from January 2000 to June 2005 at a rural teaching
      hospital. RESULTS: Four hundred forty-five patients were analyzed in two groups;
      those who underwent CT scans (N = 245) and those who did not (N = 200). Patients
      undergoing CT scans were significantly older (median age 38 vs. 22 years, P <
      0.0001), were more likely to have perforated appendicitis (P 0.001), were less
      likely to undergo a negative appendectomy (P = 0.003), and had a significantly
      longer length of stay than those who did not (P 0.009). Analysis by gender showed
      that perforation rates continued to be significantly higher in males undergoing
      CT scans (P 0.004). To examine the possibility that sicker patients were more
      likely to receive CT scans and also be found to have perforated appendicitis, a
      sensitivity analysis was performed. Patients showing perforated appendicitis on
      initial CT scans were excluded and the analysis was repeated. The difference in
      perforation rates continued to remain significant (P 0.037). CONCLUSION: Males
      undergoing CT scans are significantly more likely to have perforated
      appendicitis. A protocol-driven rational approach to CT evaluation of suspected
      appendicitis may lower perforation rates, especially in males.

PMID- 19381738
TI  - Determination of the relationship between gastric wall thickness and body mass
      index with endoscopic ultrasound.
AB  - BACKGROUND: The aim of this study was to determine the relationship between
      gastric wall thickness and BMI. METHODS: Bariatric surgery patients undergoing a
      pre-operative screening EGD and patients undergoing endoscopic ultrasound for non
      gastric pathology were prospectively enrolled in the study. Patients underwent
      endoscopic ultrasound evaluation with measurements of gastric wall thickness at
      six areas of the stomach. The primary outcome was the correlation of BMI and mean
      gastric wall thickness. RESULTS: Twenty-four patients were enrolled in the study.
      Eight patients were excluded due to endoscopic abnormalities of the stomach
      (five) or intolerance to the procedure (three). Ten patients with a normal BMI
      and six obese patients were included in the analysis. BMI in the non-obese group
      was 23.8 +/- 2.5 kg/m(2) compared to 54.7 +/- 14.6 kg/m(2) in the obese
      population. The average gastric wall thickness amongst all subjects was 3.27 +/-
      0.42 mm. Mean gastric thickness in the non-obese group was 3.25 +/- 0.45 mm
      compared to 3.30 +/- 0.39 mm in the obese group (p = 0.41). When both groups were
      combined, there did not appear to be a linear relationship between mean thickness
      and BMI (R (2) = 0.005). There was no linear relationship between gastric wall
      thickness and waist circumference (R (2) = 0.02). CONCLUSION: There was no
      significant correlation between gastric wall thickness and BMI. Mean gastric wall
      thickness of endoscopically normal stomachs was in the range of 3-4 mm.

PMID- 19381739
TI  - Prevalence of obesity among children and/or grandchildren of adult bariatric
      surgery patients.
AB  - BACKGROUND: Clinical experience suggests that some adults who undergo bariatric
      surgery have children who are obese. Childhood obesity is associated with
      increased morbidity and mortality in later life. This study examined the
      prevalence of obesity among children and grandchildren (< or =12 years of age) of
      adult bariatric surgery patients. METHODS: Patients in a prospective database of
      morbidly obese patients who underwent bariatric surgery between January 2004 and
      May 2007 were recruited by phone and in clinic. Patient demographics, body mass
      index (BMI) at surgery, and survey data were collected. The survey included
      questions regarding their child/grandchild's body habitus, weight, and height.
      Child obesity was defined as BMI percentile > or =95. Statistical significance
      was set at p < 0.05. RESULTS: One hundred twenty-two patients were enrolled in
      this study (77% women, mean BMI 49 kg/m(2)). One hundred thirty-four out of 233
      children/grandchildren identified had complete data; 41% had a BMI percentile >
      or =95. Only 29% of these obese children were so identified by the adult
      respondents. Significantly more biological children/grandchildren were obese than
      nonbiological (p = 0.013), and significantly more biological children were obese
      than biological grandchildren (p = 0.027). CONCLUSIONS: This sample of bariatric
      surgery patients had a high proportion of obese preteen children/grandchildren.
      Obesity was most prevalent among biological children (vs. biological
      grandchildren and nonbiological children). Patients often did not recognize the
      degree of overweight in their children/grandchildren. Because families of
      bariatric surgery patients often include obese children, interventions aimed at
      all family members merit consideration.

PMID- 19381740
TI  - Internal hemipelvectomy for pelvic sarcomas using a T-incision surgical approach.
AB  - Internal hemipelvectomy is performed for pelvic sarcomas when the tumor can be
      safely resected without sacrificing the entire extremity. Wide exposure and
      awareness of major neurovascular structures are crucial to the success of this
      surgery. Various modifications on the standard utilitarian approach have been
      used to best achieve these goals. We reviewed our experience using the T-incision
      technique for 30 pelvic sarcoma resections. The minimum followup was 3.6 months
      (mean, 55 months; range, 3.6-185.4 months). Postoperative complications included
      minor complications (requiring no surgery or a simple incision and drainage with
      primary closure) in 27% of patients and major complications (involving a deep
      infection or more extensive surgical treatment) in 17%. Ninety-two percent of
      wound complications healed uneventfully with antibiotics and incision and
      drainage. The 2-, 5-, and 10-year patient survival rates were 67%, 59%, and 53%.
      The 2-, 5-, and 10-year disease-free survival rates were 68%, 42%, and 42%. The
      mean Musculoskeletal Tumor Society and Toronto Extremity Salvage Scores were 69%
      and 86%, respectively. We believe the T-incision technique for internal
      hemipelvectomy is an effective surgical approach for pelvic sarcomas when limb
      salvage is possible. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 19381741
TI  - Periacetabular osteotomy: a systematic literature review.
AB  - The Bernese periacetabular osteotomy is commonly used to treat symptomatic
      acetabular dysplasia. Although periacetabular osteotomy is becoming a more common
      surgical intervention to relieve pain and improve function, the strength of
      clinical evidence to support this procedure for these goals is not well defined
      in the literature. We therefore performed a systematic review of the literature
      to define the level of evidence for periacetabular osteotomy, to determine
      deformity correction, clinical results, and to determine complications associated
      with the procedure. Thirteen studies met our inclusion criteria. Eleven studies
      were Level IV, one was Level III, and one was Level II. Radiographic deformity
      correction was consistent and improvement in hip function was noted in all
      studies. Most studies did not correlate radiographic and clinic outcomes.
      Clinical failures were commonly associated with moderate to severe preoperative
      osteoarthritis and conversion to THA was reported in 0% to 17% of cases. Major
      complications were noted in 6% to 37% of the procedures. These data indicate
      periacetabular osteotomy provides pain relief and improved hip function in most
      patients over short- to midterm followup. The current evidence is primarily Level
      IV. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 19381742
TI  - Prospective analysis of hip arthroscopy with 10-year followup.
AB  - Arthroscopic surgery of the hip is a well-established technique with numerous
      recognized indications. Despite the well-accepted nature of this procedure, there
      have been no outcomes studies with extended followup. We investigated the
      response to hip arthroscopy in a consecutive series of patients with 10 years
      followup. Since 1993, all patients undergoing hip arthroscopy have been assessed
      prospectively with a modified Harris hip score preoperatively and then
      postoperatively at 3, 12, 24, 60, and 120 months. A cohort of 50 patients (52
      hips) was identified who had achieved 10-year followup and represent the
      substance of this study. There was 100% followup. The average age of the patients
      was 38 years (range, 14-84 years), with 27 males and 23 females. The median
      improvement was 25 points (preoperative, 56 points; postoperative, 81 points).
      Fourteen patients were converted to THA and two died. Four patients underwent
      repeat arthroscopy. There were two complications in one patient. The presence of
      arthritis at the time of the index procedure was an indicator of poor prognosis.
      This study substantiates the long-term effectiveness of arthroscopy in the hip as
      treatment for various disorders, including labral pathology, chondral damage,
      synovitis, and loose bodies. Arthritis is an indicator of poor long-term outcomes
      with these reported methods. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 19381743
TI  - Healthcare quality measurement in orthopaedic surgery: current state of the art.
AB  - Improving quality of care in arthroplasty is of increasing importance to payors,
      hospitals, surgeons, and patients. Efforts to compel improvement have
      traditionally focused measurement and reporting of data describing structural
      factors, care processes (or 'quality measures'), and clinical outcomes. Reporting
      structural measures (eg, surgical case volume) has been used with varying degrees
      of success. Care process measures, exemplified by initiatives such as the
      Surgical Care Improvement Project measures, are chosen based on the strength of
      randomized trial evidence linking the process to improved outcomes. However,
      evidence linking improved performance on Surgical Care Improvement Project
      measures with improved outcomes is limited. Outcome measures in surgery are of
      increasing importance as an approach to compel care improvement with prominent
      examples represented by the National Surgical Quality Improvement Project.
      Although outcomes-focused approaches are often costly, when linked to active
      benchmarking and collaborative activities, they may improve care broadly.
      Moreover, implementation of computerized data systems collecting information
      formerly collected on paper only will facilitate benchmarking. In the end, care
      will only be improved if these data are used to define methods for innovating
      care systems that deliver better outcomes at lower or equivalent costs.

PMID- 19381744
TI  - Kaposiform hemangioendothelioma in multiple spinal levels without skin changes.
AB  - Kaposiform hemangioendothelioma is a rare vascular tumor of childhood that is
      locally aggressive but has little metastatic potential and by itself is not known
      to be lethal. It most commonly presents as a superficial or deep soft tissue mass
      with associated cutaneous lesions. Kasabach-Merritt phenomenon, a condition
      characterized by profound thrombocytopenia and life-threatening hemorrhage, often
      is associated with kaposiform hemangioendothelioma. Six cases of kaposiform
      hemangioendothelioma have been reported in bone, two of which were located in
      extracraniofacial bones. We report a diagnostically challenging case of a 6-year
      old girl with kaposiform hemangioendothelioma of the thoracolumbar spine without
      Kasabach-Merritt phenomenon or cutaneous lesions.

PMID- 19381745
TI  - Intra- and intersurgeon variability in image-free navigation system for THA.
AB  - In image-free navigation systems, cup orientation is determined in the pelvic
      coordinate by registration of bony landmarks. While the value of navigation
      relates primarily to the reliability and accuracy of cup placement, the
      reliability of registration plays a role in cup placement. We therefore examined
      intra- and intersurgeon variability in registration and the distance between
      registration points in each bony landmark. Thirty-seven THAs were performed in
      the lateral position and 15 THAs in the supine position. The cup was fixed using
      a navigation system. The registration was repeated two more times by operator and
      assistant, and the intra- and intersurgeon variability of cup abduction angle and
      anteversion was analyzed by ICC (intraclass correlation coefficients). In 25
      hips, the distance between intrasurgeon registration points and between
      intersurgeon registration points in each landmark were calculated. The ICC in the
      lateral position ranged between 0.59 and 0.81, and between 0.85 and 0.95 in the
      supine position. The ICCs of cup abduction angle for the intra- and intersurgeon
      variability were 0.92 and 0.95 for the supine position and 0.65 and 0.59 for the
      lateral position. Those of anteversion were 0.93, 0.85, and 0.81, 0.72,
      respectively. The variability in locating the ASIS in the lateral position was
      greater than that in the supine position. The variability of registration points
      depended on bony landmarks and patient position but the range of variability we
      found would not likely result in a large variability in cup placement.

PMID- 19381747
TI  - Patients with prosthetic joint infection on IV antibiotics are at high risk for
      readmission.
AB  - Due to the rise in prosthetic joint implantations, prosthetic joint infections
      (PJI) are increasing. Most PJI are treated outside the hospital setting via
      community-based parenteral antiinfective therapy (CoPAT) after initial surgical
      management, although little is reported about the short-term complications of
      CoPAT. We therefore ascertained the numbers of unanticipated readmissions,
      unplanned surgeries, and CoPAT complications within 12 weeks of hospital
      discharge in patients with PJI on CoPAT. We retrospectively reviewed the charts
      of 74 patients with PJI. Twenty-seven (73% of readmitted patients) were for
      unanticipated reasons within 12 weeks of hospital discharge; 16 (43% of
      readmitted) underwent an unplanned surgery. Nine patients (12% of total cohort)
      had CoPAT-related adverse events. Our data suggest patients with PJI on CoPAT
      represent a complex cohort that needs to be monitored closely for complications
      early after hospital discharge. LEVEL OF EVIDENCE: Level IV, therapeutic study.

PMID- 19381746
TI  - Quantification of the radiographic joint space width of the ankle.
AB  - Quantification of joint space width of the ankle could provide information
      essential to evaluate the effects of potential disease-modifying agents and
      adverse effects of devices intended to ameliorate osteoarthritis elsewhere in the
      lower extremity. Current methods require proprietary software or have not been
      well validated; our purpose was to develop and assess the reliability of a
      digital joint space width quantification method using public access software. We
      studied 95 patients, asymptomatic in the ankles and without history of ankle
      trauma, but with symptomatic medial knee osteoarthritis, participating in an
      ongoing longitudinal trial. Weightbearing anteroposterior radiographs of the
      ankle and supine radiographs of the pelvis were assessed, and the narrowest
      medial and lateral tibiotalar joint space widths and hip joint space widths were
      measured using Image J software (US NIH, Bethesda, MD). Medial joint space widths
      were 2.56 +/- 0.50 and 2.55 +/- 0.48 mm, and lateral joint space widths were 2.45
      +/- 0.55 and 2.44 +/- 0.52 mm, for right and left ankle, respectively.
      Coefficients of variation for repeat measurements by the same observer were 1.13%
      and 4.5%, and by different observers 7.30% and 7.27%, for medial and lateral
      joint space widths, respectively. Men had wider joint space widths than women
      when accounting for height. Joint space width of the ankle correlated with the
      joint space width of the hip and with height and weight, but not with age.

PMID- 19381748
TI  - Individual differences in executive functioning: implications for stress
      regulation.
AB  - BACKGROUND: Executive functioning (EF) refers to the set of neurocognitive
      processes that facilitate novel problem solving, modification of behavior in
      response to environmental changes, planning and generating strategies for complex
      actions, and ability to override pre-potent behavioral and emotional responses to
      engage in goal-directed behavior. PURPOSE: To provide an overview of research on
      individual differences in EF and examine the extent to which these individual
      differences confer risk and resilience for poor stress regulation. RESULTS:
      Review of the literature suggests that individual differences in EF are evident
      at multiple levels of analysis including genotype, endophenotype (e.g.,
      performance on cognitive tasks), and phenotype (e.g., temperament and
      personality). These individual differences are associated with differential
      stress exposure, reactivity, recovery, and restorative processes. CONCLUSIONS: A
      theoretical framework that includes individual differences in EF will inform
      behavioral medicine research on stress risk and resilience.

PMID- 19381749
TI  - [Cardiorespiratory arrest due to an air embolus from a peripheral venous line].

PMID- 19381750
TI  - An echolucent structure on the anterolateral wall of the right atrium.

PMID- 19381751
TI  - [Club foot surgery with caudal ropivacaine 0.5% in a remote location].

PMID- 19381752
TI  - Actual therapeutic efficacy of pre-transplant treatment on hepatocellular
      carcinoma and its impact on survival after salvage living donor liver
      transplantation.
AB  - BACKGROUND: The exact efficacy of pre-liver transplant (LT) therapy for
      hepatocellular carcinoma (HCC) and the impact on survival after LT remain
      controversial in regard to salvage LT. MATERIALS AND METHODS: Of 79 patients
      transplanted in Nagasaki University Hospital between August 1997 and December
      2007, 29 patients (36.7%) were indicated for HCC based on the Milan criteria
      using computed tomography and magnetic resonance imaging. Pre-LT therapy other
      than liver resection had been performed in 18 cases (62.1%) for 24 lesions.
      Treated lesions were analyzed histologically using thin slices of the whole
      explanted liver. RESULTS: Pre-LT therapy included transarterial chemoembolization
      (TACE) for 10 lesions, percutaneous ethanol injection (PEI) + TACE for 1 lesion,
      PEI in 6 lesions and ablation therapy in 7 lesions. Under preoperative imaging
      study, 19 lesions (79.1%) were "thought-to-be" necrotic by pre-LT therapy.
      However, histologically, viable HCCs were still observed in 9 lesions (9/19 47%).
      A median interval between the first pre-therapy and LT was 22 months, while last
      pre-LT therapy and LT was 11 months. No sarcomatous HCC or forced portal venous
      tumor thrombus was found in all cases with residual lesions. One peritoneal
      recurrence has occurred after LT, in whom PEI and RFA had been performed before
      LDLT. The disease free survival after LDLT was comparable to that of cases
      without pre-LT therapy. CONCLUSION: Half of the preoperatively "thought-to-be"
      necrotic lesions still contained viable HCC cells after the pre-LT treatment.
      Overall, the history of pre-LT therapy does not preclude or interfere with
      subsequent LT, although percutaneous treatment may spread disseminated tumor cell
      growth under immunosuppression.

PMID- 19381753
TI  - FIC1-mediated stimulation of FXR activity is decreased with PFIC1 mutations in
      HepG2 cells.
AB  - PURPOSE: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is a
      specific form of genetic cholestasis caused by functional defects in FIC1/ATP8B1.
      Although the way FIC1 deficiency leads to PFIC1 remains unclear, some reports
      suggest that the loss of FIC1 function results in decreased activity of the
      farnesoid X receptor (FXR) in PFIC1 patients. In this study, in order to
      elucidate the molecular mechanism of the pathogenesis of PFIC1, we constructed an
      experimental system for the evaluation of FIC1-mediated stimulatory effects on
      FXR activity. METHODS AND RESULTS: Luciferase assays revealed that FIC1
      expression increased FXR-dependent transcription and that the effects of three
      PFIC1 mutants (G308V, T456M and D554N) were smaller than that of wild-type FIC1.
      In addition, the PFIC1 mutants could not locate to the plasma membrane even in
      the presence of CDC50A, which brings wild-type FIC1 to the plasma membrane. The
      results of coprecipitation assays suggested a defect in the ability of the PFIC1
      mutants to interact with CDC50A. Furthermore, it was revealed that the expression
      of CDC50A elevated the FIC1-mediated transcriptional stimulation when coexpressed
      with wild-type FIC1, but not with mutated FIC1. CONCLUSIONS: These results
      suggest that the PFIC1 mutants have a lower stimulatory effect on FXR activity
      and cannot interact with CDC50A, which may lead to the development of the
      features of PFIC1.

PMID- 19381754
TI  - Relationship between radiological knee osteoarthritis and biochemical markers of
      cartilage and bone degradation (urine CTX-II and NTX-I): the Matsudai Knee
      Osteoarthritis Survey.
AB  - Biochemical markers of cartilage and bone degradation are becoming increasingly
      important in the evaluation of knee osteoarthritis (OA). To clarify the
      correlation between radiological knee OA and urine CTX-II (C-terminal
      crosslinking telopeptide of collagen type II) or urine NTX-I (N-terminal
      crosslinking telopeptide of type I collagen), we conducted a cross-sectional
      study in the cohorts of the epidemiological knee survey at the Matsudai district
      in Niigata Prefecture, Japan. Urine specimens were collected from 296 subjects,
      and CTX-II and NTX-I were measured using ELISA. Standing knee AP X-rays were
      obtained and graded according to the Kellgren-Lawrence classification. The
      subjects were then divided by gender, age (40- to 59-year-old group and 60- to 79
      year-old group), and the X-ray grade (Grade 0, 1, Grade 2, and Grade 3, 4). In
      non-OA (Grade 0, 1) subjects, the 60- to 79-year-old group had significantly
      higher CTX-II values than the younger group only in females. The subjects of both
      genders aged over 60 years of age with OA Grade 3, 4 had significantly higher CTX
      II values than the Grade 0, 1 group or the Grade 2 group. For NTX-I, there were
      no significant differences between each OA grade although the Grade 3, 4 group
      females from 60 to 79 years of age had higher values than the Grade 2 group. In
      addition, in the 60- to 79-year-old subjects of both genders, a positive
      correlation was observed between the urine CTX-II and urine NTX-I. For the
      subjects ranging from 60 to 79 years of age in both genders, the urine CTX-II
      values indicate the progression of OA. In addition, the weak but positive
      correlation between urine CTX-II and urine NTX-I in the subjects ranging from 60
      to 79 years of age in both genders suggests that bone resorption and cartilage
      degradation appear to develop in parallel.

PMID- 19381755
TI  - The Exiguobacterium genus: biodiversity and biogeography.
AB  - Bacteria of the genus Exiguobacterium are low G + C, Gram-positive facultative
      anaerobes that have been repeatedly isolated from ancient Siberian permafrost. In
      addition, Exiguobacterium spp. have been isolated from markedly diverse sources,
      including Greenland glacial ice, hot springs at Yellowstone National Park, the
      rhizosphere of plants, and the environment of food processing plants. Strains of
      this hereto little known bacterium that have been retrieved from such different
      (and often extreme) environments are worthy of attention as they are likely to be
      specifically adapted to such environments and to carry variations in the genome
      which may correspond to psychrophilic and thermophilic adaptations. However,
      comparative genomic investigations of Exiguobacterium spp. from different sources
      have been limited. In this study, we employed different molecular approaches for
      the comparative analysis of 24 isolates from markedly diverse environments
      including ancient Siberian permafrost and hot springs at Yellowstone National
      Park. Pulsed-field gel electrophoresis (PFGE) with I-CeuI (an intron-encoded
      endonuclease), AscI and NotI were optimized for the determination of genomic
      fingerprints of nuclease-producing isolates. The application of a DNA macroarray
      for 82 putative stress-response genes yielded strain-specific hybridization
      profiles. Cluster analyses of 16S rRNA gene sequence data, PFGE I-CeuI
      restriction patterns and hybridization profiles suggested that Exiguobacterium
      strains formed two distinct divisions that generally agreed with temperature
      ranges for growth. With few exceptions (e.g., Greenland ice isolate GIC31),
      psychrotrophic and thermophilic isolates belonged to different divisions.

PMID- 19381756
TI  - Effect of variation of environmental conditions on the microbial communities of
      deep-sea vent chimneys, cultured in a bioreactor.
AB  - Both cultivation and molecular techniques were used to investigate the microbial
      diversity and dynamic of a deep-sea vent chimney. The enrichment cultures
      performed in a gas-lift bioreactor were inoculated with a black smoker chimney
      sample collected on TAG site on the mid-Atlantic ridge. To mimic as close as
      possible environmental conditions, the cultures were performed in oligotrophic
      medium with nitrogen, hydrogen and carbon dioxide (N(2)/H(2)/CO(2)) gas sweeping.
      Also, the temperature was first settled at a temperature of 85 degrees C and
      colloidal sulphur was added. Then, the temperature was lowered to 60 degrees C
      and sulphur was omitted. Archaeal and bacterial diversity was studied in both
      culture and natural samples. Through 16S rRNA gene sequences analysis of the
      enrichment cultures microorganisms affiliated to Archeoglobales, Thermococcales
      were detected in both conditions while, Deferribacterales and Thermales were
      detected only at 65 degrees C in the absence of sulphur. Single-stranded
      conformational polymorphism and quantitative PCR permit to study the microbial
      community dynamic during the two enrichment cultures. The effect of environmental
      changes (modification of culture conditions), i.e. temperature, medium
      composition, electron donors and acceptors availability were shown to affect the
      microbial community in culture, as this would happen in their environment. The
      effect of environmental changes, i.e. temperature and medium composition was
      shown to affect the microbial community in culture, as this could happen in their
      environment. The modification of culture conditions, such as temperature, organic
      matter concentration, electron donors and acceptors availability allowed to
      enrich different population of prokaryotes inhabiting hydrothermal chimneys.

PMID- 19381757
TI  - Infective endocarditis in hemodialysis patients: clinical features,
      echocardiographic data and outcome: a 10-year descriptive analysis.
AB  - BACKGROUND: Infective endocarditis (IE) is a dreaded complication in hemodialysis
      (HD) patients and is strongly associated with morbidity and mortality.
      OBJECTIVES: Our aim was to investigate clinical and echocardiographic
      characteristics, microbiological profile, management and outcome of patients on
      HD in a Tunisian (Tunisia, North Africa) high-volume tertiary-care centre.
      METHODS: Among 182 patients who fulfilled the modified Duke criteria for
      infective endocarditis between January 1997 and December 2006, 16 were on chronic
      HD and were included in the study. RESULTS: Mean age was 52.5 +/- 22.3 years, ten
      were male and arteriovenous fistulas were the most commonly used access sites (12
      out of 16 cases). Average duration of dialysis was 27.3 +/- 30 months. Major
      causative organisms were Staphylococcus species (including methicillin-resistant
      Staphylococcus aureus) in 11 (68.7%) of the 16 cases. The mitral valve was the
      most commonly affected [9 patients out of 16 (56.2%)], followed by aortic valve
      in 4 cases (25.0%) and tricuspid valve in 1 case (6.2%). Complications were
      frequent, including congestive heart failure (56.2%), secondary septic
      localisations (31.2%), arterial emboli (18.7%), and cerebral haemorrhage (6.2%).
      Five patients underwent surgery and seven died during hospitalization (43.7%
      mortality rate). No recurrences of IE were recorded in the nine survivors after
      average 21.7 +/- 17.3 months follow-up. CONCLUSION: In this largest reported
      confirmed IE series in dialysis patients in a developing country, mortality was
      very high; mitral valve was the most commonly affected valve. Staphylococcus
      species were the major causative organisms.

PMID- 19381758
TI  - Nephrotic-range proteinuria in a patient with a renal allograft treated with
      sorafenib for metastatic renal-cell carcinoma.
AB  - A 51-year-old man with immunoglobulin A (IgA) nephropathy developed metastatic
      renal-cell carcinoma of his native right kidney, 3.5 years post kidney
      transplant. At that time renal function was stable with the presence of only mild
      proteinuria. Shortly after chemotherapy with sorafenib [anti-vascular endothelial
      growth factor (VEGF)] was initiated, progressive renal impairment, hypertension,
      and nephrotic-range proteinuria developed. Allograft biopsy showed extensive IgA
      nephropathy. After withdrawal of the anti-VEGF therapy, however, renal function
      and blood pressure improved, and proteinuria diminished. Based on the clinical
      course and histopathological findings we hypothesize that sorafenib may induce
      nephrotic-range proteinuria and renal impairment, possibly through anti-VEGF
      mediated effects on the progression of IgA nephropathy.

PMID- 19381759
TI  - Ultrasonography as a predictor of overt bleeding after renal biopsy.
AB  - BACKGROUND: Renal biopsy is essential for the diagnosis of kidney diseases, but
      complications, particularly bleeding incidents, remain problematic. METHODS: To
      evaluate the frequency of renal biopsy complications, and to reveal clinical and
      laboratory factors associated with overt bleeding complications, focusing on
      those available at hospital ward, we conducted a retrospective observational
      study for the period between 2001 and 2005 at Mie University Hospital in patients
      who underwent percutaneous renal biopsy of a native kidney. Of a total of 323
      patients, 317 met the inclusion criteria. RESULTS: Only one patient (0.3%)
      required blood transfusion or intervention to stop bleeding. The mean decrease in
      hemoglobin (Hb) after biopsy was 0.43 +/- 0.7 g/dL. Hb decreased > or =1.0 g/dL
      in 66 patients (20.8%) and > or =10% in 32 patients (10.1%). On ultrasonography,
      perirenal hematoma was detected immediately after biopsy in 273 patients (86.1%),
      and 41 patients (12.9%) showed hematoma > or =2 cm in width. Analgesics were
      required for back pain in 67 patients (21.1%). Vasovagal response developed in 31
      patients (9.8%). Macrohematuria occurred in 12 patients (3.8%). Urinary catheter
      was used in 161 patients (50.8%). For Hb decrease > or =10% after biopsy,
      multivariate analysis revealed perirenal hematoma (> or =2 cm) as a significant
      factor. Other significant factors were prolonged international normalized ratio
      of prothrombin time, elevated blood pressure on hospital admission, older age,
      increased serum creatinine level, and steroid use. CONCLUSION: Perirenal hematoma
      > or =2 cm on ultrasonography immediately after biopsy might well represent a
      predictive factor for bleeding complications.

PMID- 19381760
TI  - (99m)Tc-TRODAT-1 and (123)I-IBZM SPECT studies in a patient with extrapontine
      myelinolysis with parkinsonian features.
AB  - Osmotic demyelination syndrome can result from the rapid correction of
      hyponatremia, and is categorized by central pontine myelinolysis and extrapontine
      myelinolysis (EPM). Magnetic resonance imaging (MRI) is currently the most useful
      modality for visualizing EPM lesions. However, MRI is unable to delineate the
      severity of involvement in the nigrostriatal dopaminergic pathway. The authors
      describe the case of a 48-year-old woman who developed isolated EPM with
      predominantly right-sided parkinsonian symptoms after rapid correction of
      hyponatremia. MRI revealed symmetrical demyelinating lesions in the bilateral
      striatum without central pontine involvement. (99m)Tc-TRODAT-1 and (123)I
      iodobenzamide ((123)I-IBZM) single-photon emission computed tomography (SPECT)
      images showed unequally decreased uptake in the bilateral striatum. Treatment
      with carbidopa/levodopa improved the clinical parkinsonian symptoms. (99m)T(C)
      TRODAT-1 and (123)I-IBZM SPECT images provide presynaptic and postsynaptic
      molecular information of the nigrostriatal dopaminergic pathway. The lesions
      demonstrated in the (99m)T(C)-TRODAT-1 and (123)I-IBZM SPECT images show higher
      correlation with the severity of clinical features in EPM than MRI, and the
      modalities may be useful in the evaluation of patients with parkinsonian
      symptoms.

PMID- 19381761
TI  - Use of tranexamic acid for disseminated intravascular coagulation with excessive
      fibrinolysis associated with aortic dissection in a patient with chronic renal
      failure.

PMID- 19381762
TI  - Rare association of Hodgkin lymphoma, Graves' disease and myasthenia gravis
      complicated by post-radiation neurofibrosarcoma: coincidence or genetic
      susceptibility?
AB  - With Hodgkin lymphoma (HL), other (autoimmune) diseases may occasionally occur or
      associate, whereas as a late treatment-complication, second tumour may develop.
      In our patient HL was diagnosed in 1996 and consequently received COPP/ABV and
      mantle irradiation. Due to the residual mediastinal tumour CRu was declared but
      later on no progression/relapse could be proved by PET. In 2000 Graves's disease,
      in 2001 myasthenia gravis was diagnosed, which showed resistance for
      immunosuppressant drugs, thus plasmapheresis, intravenous immunoglobulin
      treatments were applied. In 2005, the residual mediastinal tumour started
      progressive growth, which leads to thoracotomy in which the tumour was removed,
      it was malignant peripheral nerve sheath tumour. The disease showed progression
      despite the chemotherapy applied and the patient died in 2007 due to respiratory
      failure. Not even the postmortem histopathologic examination revealed the relapse
      of HL. Association of Hodgkin lymphoma, and two antibody-mediated autoimmune
      diseases, Graves' disease and myasthenia gravis, is rare and has not yet been
      reported in the literature. The etiologic role of genetic predisposition and
      immune regulatory disorder must definitely be thought of, as the possibility of
      mere coincidence is extremely small. Malignant peripheral nerve sheath tumour is
      a rare complication of irradiation, which underlines the importance of the risk
      or/and response adapted therapy of HL.

PMID- 19381763
TI  - Fetal MRI with diffusion-weighted imaging (DWI) and apparent diffusion
      coefficient (ADC) assessment in the evaluation of renal development: preliminary
      experience in normal kidneys.
AB  - PURPOSE: The study aimed to investigate the correlation between apparent
      diffusion coefficient (ADC) and gestational age by applying diffusion-weighted
      imaging (DWI) in the study of normal fetal kidneys. MATERIALS AND METHODS: We
      performed magnetic resonance (MR) imaging on 88 fetuses (gestational age range 17
      40 weeks) after ultrasound had ruled out urinary system malformations. A
      multiplanar study of the urinary system was obtained by using conventional T2
      weighted sequences and echoplanar imaging (EPI). DW sequences with ADC maps were
      subsequently acquired, and kidney ADC values were correlated with gestational age
      by diving the fetuses into six groups according to age. RESULTS: We found a
      correlation between ADC values and gestational age. The ADC values, ranging from
      0.99 to 1.62x10(-3) mm(2)/s [mean 1.22; 95% confidence interval (CI) 1.19-1.25,
      standard deviation (SD) 0.147], showed a tendency to decrease with increasing
      gestational age. The relationship between ADC values and gestational age was
      expressed by a linear regression equation: ADC (mm(2)/s)=1.69-0.0169 (GA)
      (R(2)=37.7%, R(2) ADJ=37.0%, p<0.005, Pearson correlation=-0.614). CONCLUSIONS:
      DWI with ADC mapping provides functional information on fetal renal parenchyma
      development and may thus become a useful tool in the management of pregnancy and
      treatment of the newborn child.

PMID- 19381765
TI  - Dopamine agonist-based strategies in the treatment of Parkinson's disease.
AB  - More therapeutic options have become available for Parkinson's disease (PD) in
      recent years, leading to significant improvements in motor control both at early
      and advanced disease stages. More importantly, the need to expand disease
      management beyond motor symptom control has been recently highlighted and
      contribution of non-motor features to quality of life is now relevant. Dopamine
      agonists represent a valid therapeutic option in PD and their effect on non-motor
      domains like mood or cognition is now acknowledged as a key factor in fully
      addressing patients' needs. Pramipexole is a well established dopamine agonist
      that is currently being investigated for its potential disease-modifying effect
      and action on mood in PD. In this review we will examine factors contributing to
      treatment decision-making and discuss how a proper balance between motor and non
      motor features should be aimed for in approaching PD therapy.

PMID- 19381764
TI  - Assessment of left main coronary artery atherosclerotic burden using 64-slice CT
      coronary angiography: correlation between dimensions and presence of plaques.
AB  - PURPOSE: The aim of this study was to correlate left main (LM) coronary artery
      dimensions with the presence of atherosclerosis by multidetector-row computed
      tomography (MDCT) coronary angiography (CA) and to assess coronary
      atherosclerotic plaques with a semiquantitative method. MATERIALS AND METHODS:
      Sixty-two consecutive patients (41 men, mean age 60+/-11) with suspected coronary
      artery disease underwent 64-MDCT coronary angiography. LM dimensions (length,
      ostial and bifurcation diameters), quantitative [location, Hounsfield unit (HU)
      attenuation] and qualitative (composition, shape) analysis of plaques within the
      LM were performed. All patients underwent conventional CA. RESULTS: Thirty
      patients (mean age 55+/-10) without plaques in the LM presented the following
      average dimensions: length 10.6+/-6.1 mm, ostial diameter 5.5+/-0.7 mm,
      bifurcation diameter 4.9+/-0.9 mm. LM plaques (n=36) were detected in 32 patients
      (mean age 64+/-10) with the following LM average dimensions: length 11.3+/-4.0
      mm, ostial diameter 6.0+/-1.2 mm and bifurcation diameter 6.0+/-1.2 mm. Plaques
      were calcified (40%, mean attenuation 742+/-191 HU), mixed (43%, mean attenuation
      387+/-94 HU) or noncalcified (17%, mean attenuation 56+/-14 HU) and were
      frequently eccentric (77%). Age was significantly different in the two groups
      (p<0.05). LM diameters of patients with plaques were improved (p<0.05). A
      moderate correlation was found between the LM bifurcation diameter and the
      corresponding plaque area (r=0.56). Significant conventional CA lesions of the LM
      were present in just three patients (5%). CONCLUSIONS: Increased LM diameters are
      associated with the presence of atherosclerosis. MDCT CA indicates relevant
      features of LM atherosclerotic burden, as rupture and subsequent thrombosis of
      vulnerable plaques may develop from lesions characterised as nonsignificant at
      conventional CA.

PMID- 19381766
TI  - Dopamine agonists and therapy compliance.
AB  - Dopamine replacement therapy in Parkinson's disease improves motor symptoms,
      however some patients suffer from motor and behavioural disturbances attributable
      to taking doses of medication well beyond the dose required to treat their motor
      disabilities. Dopamine dysregulation syndrome (DDS) can be regarded as a pattern
      of compulsive medication use, leading to disabling motor and behavioural
      features. DDS, probably attributed to pulsatile overstimulation of the limbic
      dopaminergic system, is characterised by severe dopamine addiction and
      behavioural disorders such as pathological gambling (PG), hypersexuality, punding
      and mood swings. PG is a form of impulse control disorder (ICD), consisting of
      persistent and maladaptive gambling of various types, which affects personal,
      family and occupational activity. The treatment of the syndrome is difficult,
      hence a strict adherence to antiparkinson medication should be encouraged for
      prevention.

PMID- 19381767
TI  - Optimising levodopa therapy.
AB  - Levodopa is still recognised to be the "gold standard" symptomatic treatment for
      Parkinson's disease. After 4-5 years however, its clinical efficacy declines and
      patients may experience the so-called "long-term levodopa syndrome", which
      represents the clinical counterpart of the changes of pharmacodynamic response to
      the drug. Long duration response (LDR) is substituted by the short duration
      response (SDR), which is responsible for the fluctuations of the clinical
      response. Strategies aimed at maintaining the clinical benefits for as long as
      possible and postponing the occurrence of motor complications as late as possible
      have been at the centre of scientific debates in recent years. We are still far
      from optimal use of the drug in the different stages or the disease, both
      regarding mode of administration and dose adjustment to individual needs.

PMID- 19381768
TI  - Clinical experience of tolcapone in advanced Parkinson's disease.
AB  - We are reporting our clinical experience in 66 patients with advanced Parkinson's
      disease (PD) who were switched to tolcapone because of persisting off periods
      despite treatment with entacapone (according to the European Agency for the
      Evaluation of Medicinal products: EMEA). We used UPDRS II-III-IV in "on" state to
      monitor tolcapone effectiveness at 6 and 12 months. We found significant
      reductions in mean off-time duration (UPDRS item 39) and levodopa dose at follow
      up. Eleven patients dropped out (17%) during the first month of treatment, 2 (3%)
      because liver enzymes exceeded normal limit. Amongst patients who continued
      tolcapone, 30/55 (54%) reported "off-time" reduction > or =25% (UPDRS-39
      decrement > or =1 point). Our findings indicate that tolcapone widens the
      levodopa therapeutic window, even in patients who have not benefited from
      entacapone. We suggest that tolcapone is indicated before patients are referred
      for more invasive procedures.

PMID- 19381769
TI  - Use of apomorphine in Parkinson's disease.
AB  - In the parkinsonian patient, the striatal levels of dopamine strictly depend on
      peripheral levodopa levels; short half-life of levodopa is responsible for
      plasmatic level fluctuations, which are consistent with a pulsatile receptor
      stimulation of the striatal system. This sort of non-physiologic stimulation
      induces a change of the condition of post-synaptic neurons, which is considered
      responsible for the fluctuations of clinical response. In this respect,
      apomorphine administration, via infusion pump, may be a good therapeutic option,
      aimed at obtaining continuous receptor stimulation, assisting in the management
      of motor fluctuations in the advanced phase of the disease.

PMID- 19381770
TI  - Continuous dopaminergic stimulation achieved by duodenal levodopa infusion.
AB  - Continuous dopaminergic stimulation is the ideal approach for the management of
      Parkinson's disease (PD); this goal can be partially reached with dopamine
      agonists, but the need for a therapeutic strategy providing a strong and constant
      dopaminergic stimulation also in the advanced phase of the disease remains unmet.
      The application of levodopa/carbidopa-gel suspension directly in the duodenum
      (Duodopa) allows a continuous delivery by a portable pump, resulting in smoother
      levodopa plasmatic concentrations, and consequently in a physiologic continuous
      receptor stimulation. Clinical studies have demonstrated that duodenal infusion
      was associated with significantly better outcome compared to conventional
      treatment regarding global functioning, ability to walk, "off" time and motor
      fluctuations. A retrospective analysis of the long-term clinical experience with
      Duodopa evidenced that daily dose of levodopa decreased by 5% during follow-up.
      The profile of pharmacological adverse events of Duodopa was similar to that
      observed with oral administration; dislocation of the intestinal tube to the
      stomach was the most common technical problem.

PMID- 19381771
TI  - Subthalamic nucleus stimulation in Parkinson's disease.
AB  - Deep brain stimulation (DBS) is an effective surgical treatment for advanced
      Parkinson's disease (PD), with significant advantages in morbidity-mortality and
      quality of life when compared to lesion techniques such as thalamotomy and/or
      pallidotomy. The procedure is indicated in patients with severe resting tremor,
      unresponsive to conventional medical treatment or with motor complications. The
      most commonly reported complications in the intra- and post-surgical period are
      aborted procedure, misplaced leads, intracranial haemorrhage, seizures and
      hardware complications, whereas in the long-term period, cognitive and
      psychiatric complications can be observed. The most important eligibility
      criteria for DBS are: a correct diagnosis of idiopathic PD, severity of illness,
      a consistent levodopa response and absence of cognitive impairment. Chronological
      age and mood disorders may be relative contraindications to be individually
      evaluated. Tremor, rigidity dystonias and dyskinesias improve dramatically after
      DBS; freezing, postural instability and falls remain unchanged, whereas verbal
      fluency and dysarthria are known to worsen.

PMID- 19381772
TI  - The rationale for improved integration between home care and neurology hospital
      services in patients with advanced Parkinson's disease.
AB  - Management of patients with advanced Parkinson's disease (PD) should benefit from
      improved integration between in-hospital services and home care. In Italy the
      number of PD hospital admissions is large but there are no guidelines of
      appropriateness to address queries of health authorities on resource allocation.
      Reasons for hospitalisation are often linked primarily to the occurrence of falls
      or infections leading to admission in internal medicine wards rather than
      neurology. This could be reduced if severe patients were provided with regular
      nursing and rehabilitation services at their homes and neurologists were actively
      involved in this process. Moreover, the application of infusion therapies
      (apomorphine or duodenal levodopa infusion) or deep brain stimulation would
      require integration with home care services after patient discharge. Here we
      propose a management algorithm that we believe would facilitate care and
      eventually lead to an optimisation of resource allocations for advanced PD
      patients. This would reduce unnecessary internal medicine hospitalisations and
      further highlight the role of neurologists as a key health care figure.

PMID- 19381774
TI  - Cytochrome P450 2E1 gene polymorphisms/haplotypes and Parkinson's disease in a
      Swedish population.
AB  - Cytochrome P450 2E1 (CYP2E1), which inter alia is located in dopamine containing
      neurons in the substantia nigra, has been hypothesized to be of importance for
      the pathophysiology of Parkinson's disease (PD), either by its production of
      reactive oxygen species (ROS) or by its capability to detoxify putative
      neurotoxins. Numerous polymorphisms in the coding and non-coding regions of the
      gene for this enzyme have been reported. Different variants may account for inter
      individual differences in the activity of the enzyme or production of ROS. In
      this study, the CYP2E1 gene was examined in a control population (n = 272) and a
      population with PD (n = 347), using a tag-single nucleotide polymorphism (tSNP)
      approach founded on HapMap Data. Six tSNPs were used in the analysis and
      haplotype block data were obtained. In case of significance, the SNP was further
      examined regarding early/late age of disease onset and presence of relatives with
      PD. We found an association between allele and genotype frequencies of the C/G
      polymorphism at intron 7 (rs2070676) of this gene and PD (P value of 0.026 and
      0.027, respectively). Furthermore, analysis of the rs2070676 polymorphism in
      subgroups of patients with age of disease onset higher than 50 years and those
      not having a relative with PD also demonstrated a significant difference with
      controls. This was seen in both genotype (corresponding to P value = 0.039 and
      0.032) and allele (P = 0.027 and 0.017 respectively) frequency. As a
      representative of many polymorphisms or in possible linkage disequilibrium with
      other functional variants, it is possible that rs2070676 could influence the
      regulation of the enzyme. In conclusion, our results display an association
      between the rs2070676 polymorphism and PD. Additional investigations are needed
      to elucidate the importance of this polymorphism for the activity of CYP2E1 and
      PD susceptibility.

PMID- 19381775
TI  - Genome analysis and characterization of a tobacco mosaic virus isolate infecting
      balsam (Impatiens balsamina).
AB  - The complete RNA genomic sequence of a tobacco mosaic virus isolate infecting
      Impatiens balsamina, designated as TMV-IM, has been determined. The genomic
      sequence and the predicted gene products of TMV-IM were similar to those of other
      members of the genus Tobamovirus. The CP ORF of TMV-IM showed sequence identities
      of 95.0-99.5% with the corresponding ORFs of other TMV strains. Full-length cDNA
      of TMV-IM was amplified by RT-PCR with a 5'-end primer harboring a T7 promoter
      sequence and a 3'-end TMV-specific primer. Subsequently, the full-length cDNA was
      cloned into plasmid vectors. Capped transcripts synthesized from the cDNA clone
      were highly infectious and caused characteristic symptoms in balsam plants,
      similar to wild-type TMV-IM and TMV-U1. These results provide definitive evidence
      for the natural occurrence of TMV in balsam.

PMID- 19381776
TI  - Methods of the site-selective solid phase synthesis of peptide-derived Amadori
      products.
AB  - Two procedures of glycated peptides' synthesis have been developed. The first
      method involves reductive alkylation of the epsilon-amino groups of lysine with
      2,3:4,5-di-O-isopropylidene-beta-D-arabino-hexos-2-ulo-2,6-pyranose in the
      presence of sodium cyanoborohydride on solid support. The second one uses a new
      fully protected lysine derivative, which is a building block designed for direct
      introduction of the glycated lysine moiety into a peptide, according to the
      standard solid phase synthesis protocol. The applicability of the proposed
      methods for the synthesis of peptide-derived Amadori products is discussed. The
      structure of the synthesized glycated peptides was confirmed by high-resolution
      mass spectrometry and enzymatic hydrolysis. Circular dichroism studies, performed
      in water solution, revealed that the formation of the Amadori rearrangement
      product in the lysine side chain does not influence significantly the
      conformational preferences of the peptides studied. However, when the solvent was
      changed to trifluoroethanol, the glycated peptides preferred beta-turn
      conformation.

PMID- 19381778
TI  - Profiling histidine dipeptides in plasma and urine after ingesting beef, chicken
      or chicken broth in humans.
AB  - The in vitro metabolic stability of histidine-dipeptides (HD), carnosine (CAR)
      and anserine (ANS), in human serum, and their absorption kinetics after ingesting
      pure carnosine or HD rich foods in humans have been investigated. Healthy women
      (n = 4) went through four phases of taking one dose of either 450 mg of pure
      carnosine, 150 g beef (B), 150 g chicken (C), or chicken broth (CB) from 150 g
      chicken with a >2-week washout period between each phase. Blood samples were
      collected at 0, 30, 60, 100, 180, 240, and 300 min, and urine samples before and
      after (up to 7 h) ingesting pure carnosine or food. Both plasma and urine samples
      were analyzed for HD concentrations using a sensitive and selective LC-ESI-MS/MS
      method. CAR was undetectable in plasma after ingesting pure carnosine, B, C or
      CB. By contrast, plasma ANS concentration was significantly increased (P < 0.05)
      after ingesting C or CB, respectively. Urinary concentrations of both CAR and ANS
      were 13- to 14-fold increased after ingesting B, and 14.8- and 243-fold after CB
      ingestion, respectively. Thus, dietary HD, which are rapidly hydrolyzed by
      carnosinase in plasma, and excreted in urine, may act as reactive carbonyl
      species sequestering agents.

PMID- 19381777
TI  - Mitochondrial damage, cytotoxicity and apoptosis in iron-potentiated alcoholic
      liver fibrosis: amelioration by taurine.
AB  - Taurine effectively prevents ischemia-induced apoptosis in the cardiomyocytes and
      hypothalamic nuclei. The present study explores the influence of taurine on
      mitochondrial damage, oxidative stress and apoptosis in experimental liver
      fibrosis. Male albino Wistar rats were divided into six groups and maintained for
      a period of 60 days as follows: Group I, control; Group II, ethanol treatment [6
      g/(kg/day)]; Group III, fibrosis induced by ethanol and iron (0.5% w/w); Group
      IV, ethanol + iron + taurine (2% w/v); Group V, ethanol + taurine treatment and
      Group VI, control + taurine treatment. Hepatocytes isolated from ethanol plus
      iron-treated rats showed decreased cell viability and redox ratio, increased
      reactive oxygen species formation, lipid peroxidation, DNA fragmentation, and
      formation of apoptotic bodies. Liver mitochondria showed increased susceptibility
      to swell, diminished activities of mitochondrial respiratory chain complexes and
      antioxidants. Taurine administration to fibrotic rats restored mitochondrial
      function, reduced reactive oxygen species formation, prevented DNA damage, and
      apoptosis. Thus taurine might contribute to the amelioration of the disease
      process.

PMID- 19381779
TI  - D-Aspartic acid induced oxidative stress and mitochondrial dysfunctions in testis
      of prepubertal rats.
AB  - Previously we demonstrated the potential of D-aspartic acid (D-Asp), an acidic
      amino acid to induce oxidative response in prepubertal rat testis in vitro. In
      the present study, we determined the extent of oxidative stress in the testis of
      prepubertal rats that were administered D-Asp (100 and 500 mg/kg bw/d, i.p. 7
      days). D-Asp treatment significantly elevated the levels of reactive oxygen
      species, malondialdehyde and hydroperoxide in cytosol and mitochondria of testis,
      which were accompanied by enhanced glutathione levels, elevated activities of
      glutathione-dependent enzymes and catalase suggesting a state of oxidative
      stress. Further, the activities of D-aspartate oxidase and 3beta-hydroxy steroid
      dehydrogenase were elevated in the testis. The testis mitochondria of D-Asp
      treated rats showed altered citric acid and complex enzyme activities, reduction
      in membrane potential, increased permeability and intracellular Ca(2+) levels.
      Collectively, these findings suggest the potential of D-Asp to induce oxidative
      perturbations in the testis of prepubertal rats and this mechanism may in part be
      responsible for the observed physiological effects.

PMID- 19381781
TI  - Association of -394C>G and -420C>G polymorphisms in the RETN gene with T2DM and
      CHD and a new potential SNP might be exist in exon 3 of RETN gene in Chinese.
AB  - Genetic variations of the human RETN gene are associated with metabolic
      phenotypes, including obesity, insulin sensitivity, diabetes, and coronary heart
      disease (CHD). There are few studies of two gene variants, -394C>G and -420C>G,
      in Chinese population. This study investigated the distribution of RETN gene,
      single nucleotide polymorphisms (SNPs), in Chinese Han population and the
      association of the polymorphisms with type 2 diabetes mellitus (T2DM) and CHD. In
      a population-based, case-control genetic association study, a total of 961
      subjects were recruited from the community, including 318 T2DM patients, 273 CHD
      patients, and 370 unrelated healthy control individuals. Serum lipid levels were
      detected. Two SNPs of RETN gene, -394C>G and -420C>G, were genotyped by PCR-RFLP.
      Unknown Polymorphisms were screened with the technique of denaturing high
      performance liquid chromatography (DHPLC). The frequencies of RETN -394G allele
      in T2DM group, CHD group, and control group were 0.3066, 0.3555, and 0.3481,
      respectively, which are met with the Hardy-Weinberg equilibrium. There is a
      significant difference of the comparison of sex in T2DM group of RETN gene SNP
      394C>G (P < 0.05). Compared with controls, there was no significant difference in
      the distribution of genotypes and allele frequencies of -394C>G polymorphic site
      in T2DM patients and CHD patients, respectively. No direct association was found
      between the -394C>G polymorphism and T2DM or CHD. The frequencies of RETN -420G
      allele in T2DM group, CHD group, and control group were 0.4009, 0.3725, and
      0.3859, respectively, which are met with the Hardy-Weinberg equilibrium. The
      frequencies of RETN -420G allele in T2DM groups and control groups of Chinese
      population are significantly different from those in European population (0.40
      vs. 0.27, 0.39 vs. 0.26) (P < 0.01). Compared with controls, there was no
      significant difference in distribution of genotypes and allele frequencies of 
      420C>G polymorphic site in T2DM patients and CHD patients, respectively. No
      direct association was found between the -420C>G polymorphism and T2DM or CHD. In
      addition, we found new potential SNP +593G>C in exon 3 of RETN gene using DHPLC.
      The RETN gene exhibits sex and ethnic differences. +593G>C of RETN gene might be
      a new potential SNP in exon 3 of RETN gene. Association between SNP -394C>G and 
      420C>G of RETN gene with T2DM and CHD in Chinese needs more exploration.

PMID- 19381782
TI  - S655 phosphorylation enhances APP secretory traffic.
AB  - Cellular protein phosphorylation regulates proteolytic processing of the
      Alzheimer's Amyloid Precursor Protein (APP). This appears to occur both
      indirectly and directly via APP phosphorylation at residues within cytoplasmic
      motifs related to targeting and protein-protein interactions. The sorting signal
      (653)YTSI(656) comprises the S655 residue that can be phosphorylated by PKC,
      particularly in mature APP molecules. The YTSI domain has been associated with
      APP internalization and Golgi polarized sorting, but no functional significance
      has been attributed to S655 phosphorylation thus far. Using APP(695)-GFP S655
      phosphomutants we show that S655 phosphorylation is a signal that positively
      modulates APP secretory traffic. The phosphomimicking and dephosphomimicking S655
      mutants exhibited contrasting Golgi dynamics, which correlated with differential
      Golgi vesicular exit and secretory cleavage to sAPP. The role of S655
      phosphorylation in APP trafficking at sorting stations, such as the Golgi, its
      contribution toward cytoprotective alpha sAPP production, and implications for
      Alzheimer's disease are discussed.

PMID- 19381783
TI  - Double knockout Nme1/Nme2 mouse model suggests a critical role for NDP kinases in
      erythroid development.
AB  - Nm23/NDP kinases A and B encoded by the Nme1/Nme2 genes are multifunctional
      enzymes responsible for the majority of NDP kinase activity in mammals. This
      review summarizes recent studies on their physiological roles using a mouse model
      in which both Nme1 and Nme2 genes have been deleted. The double knockout mice are
      stunted in growth and die perinatally. Additionally, these mice display
      hematologic phenotypes, including severe anemia, abnormal erythroid cell
      development, loss of the iron transport receptor molecule TfR1, and reduced iron
      uptake by Nme1 ( -/- ) /Nme2 ( -/- ) erythroid cells. We hypothesize that
      Nm23/NDP kinases regulate TfR1 gene expression in erythroid cells in some manner,
      and that defective iron transport into these cells is responsible for the anemia
      and death. This Nme1/Nme2 mouse model also links nucleotide metabolism with
      erythropoiesis, suggesting alternative or additional mechanisms that may explain
      the observed phenomena.

PMID- 19381780
TI  - Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular
      disease.
AB  - Chronic inflammation is being shown to be increasingly involved in the onset and
      development of several pathological disturbances such as arteriosclerosis,
      obesity, diabetes, neurodegenerative diseases and even cancer. Treatment for
      chronic inflammatory disorders has not been solved, and there is an urgent need
      to find new and safe anti-inflammatory compounds. Flavonoids belong to a group of
      natural substances occurring normally in the diet that exhibit a variety of
      beneficial effects on health. The anti-inflammatory properties of flavonoids have
      been studied recently, in order to establish and characterize their potential
      utility as therapeutic agents in the treatment of inflammatory diseases. Several
      mechanisms of action have been proposed to explain in vivo flavonoid anti
      inflammatory actions, such as antioxidant activity, inhibition of eicosanoid
      generating enzymes or the modulation of the production of proinflammatory
      molecules. Recent studies have also shown that some flavonoids are modulators of
      proinflammatory gene expression, thus leading to the attenuation of the
      inflammatory response. However, much work remains to be done in order to achieve
      definitive conclusions about their potential usefulness. This review summarizes
      the known mechanisms involved in the anti-inflammatory activity of flavonoids and
      the implications of these effects on the protection against cancer and
      cardiovascular disease.

PMID- 19381784
TI  - Potential contributions of antimutator activity to the metastasis suppressor
      function of NM23-H1.
AB  - nm23-h1 is a well-documented metastasis suppressor gene whose mechanism(s) of
      action have yet to be fully elucidated. The purpose of this report is to discuss
      recent advances in investigating the potential role of a novel 3'-5' exonuclease
      activity identified recently in our laboratory, a biochemical function
      associated, in general, with DNA repair and replication. We have employed a site
      directed mutagenesis approach to demonstrate that the 3'-5' exonuclease activity
      of NM23-H1 is required for its metastasis suppressor function. Consistent with a
      role in DNA repair, we also observe that the single yeast NM23 homolog (YNK1) is
      required for the maintenance of genomic integrity and normal kinetics of DNA
      repair in response to exposure to ultraviolet radiation. These results and their
      implications for understanding the molecular mechanisms underlying NM23-H1
      functions in cancer are discussed.

PMID- 19381785
TI  - Role of nm23 in the regulation of cell shape and migration via Rho family GTPase
      signals.
AB  - Rho family small GTPase plays a key role in the regulation of cell shape and
      migration in mammalian cells. Constitutive activation of Rho GTPase leads to the
      aberrant cell morphology and migration. We identified nm23-H2 as a binding
      partner of Lbc proto-oncogene product, which specifically activates RhoA, and
      revealed that nm23-H2 could act as a negative regulator of Rho activity.
      Furthermore, we found that Lbc, nm23-H2 and ICAP1-alpha could form tertial
      complex in cells, and this complex formation was thought to be critical for cell
      migration stimulated by integrin. It is reported that nm23-H1 bound to Tiam1 and
      Dbl, which activates Rac and Cdc42 small GTPase, respectively. We discuss the
      role of nm23 in the regulation of cell morphology and cell migration via Rho
      family GTPases.

PMID- 19381786
TI  - The impact of managing school-aged children's diabetes: the role of child
      behavior problems and parental discipline strategies.
AB  - Models of diabetes management in children emphasize family relationships,
      particularly parent-child interactions. In adolescents, parental involvement in
      disease-specific management relates to better health and adherence. However,
      information about parental involvement in disease management for young children
      is limited and mixed. This study investigated behavior problems of school-aged
      children with Type 1 Diabetes Mellitus (T1DM) in association with parent
      discipline strategies and parents' perceptions of (1) time spent managing
      diabetes and (2) the impact their child's diabetes has on their discipline
      strategies. Parents of children ages 5-12 with T1DM completed standardized
      measures of child misbehavior, parent discipline strategies, and responded to
      questions regarding perceived time spent managing diabetes, and perceived impact
      of diabetes on ability to discipline. Results showed child mealtime misbehavior
      was common and associated with overreactive parental discipline. Further,
      overreactive discipline was also associated with reports of less time spent
      managing child's illness. Child misbehavior was positively associated with
      parents' perceived amount of time spent managing diabetes and with the impact of
      child diabetes on discipline. Findings suggest the importance of considering
      parent discipline strategies and child misbehavior when working with young
      children with diabetes.

PMID- 19381787
TI  - Do visually salient stimuli reduce children's risky decisions?
AB  - Children tend to overestimate their physical abilities, and that tendency is
      related to risk for unintentional injury. This study tested whether or not
      children estimate their physical ability differently when exposed to stimuli that
      were highly visually salient due to fluorescent coloring. Sixty-nine 6-year-olds
      judged physical ability to complete laboratory-based physical tasks. Half judged
      ability using tasks that were painted black; the other half judged the same
      tasks, but the stimuli were striped black and fluorescent lime-green. Results
      suggest the two groups judged similarly, but children took longer to judge
      perceptually ambiguous tasks when those tasks were visually salient. In other
      words, visual salience increased decision-making time but not accuracy of
      judgment. These findings held true after controlling for demographic and
      temperament characteristics.

PMID- 19381789
TI  - Precision and recall of search strategies for identifying studies on return-to
      work in Medline.
AB  - INTRODUCTION: The purpose of this study was to report on the qualities of various
      search strategies and keywords to find return to work (RTW) studies in the
      Medline bibliographic database. METHODS: We searched Medline for articles on RTW
      published in 2003, using multiple search strings, and hand searched 16 major
      periodicals of rehabilitation or occupational medicine. Among the retrieved
      articles, those considered to be relevant, were pooled in a Gold Standard
      Database. From this database, we identified candidate text words or MeSH terms
      for search strategies using a word frequency analysis of the abstracts and a
      MEDLINE categorization algorithm. According to the frequency of identified terms,
      searches were run for each term independently and in combination. We computed
      Recall, Precision, and number needed to read (NNR = 1/Precision) of each keyword
      or combination of keywords. RESULTS: Among the 8,073 articles examined, 314
      (3.9%) were considered relevant and included in the Gold Standard Database. The
      search strings ("Rehabilitation, Vocational" [MeSH]), ("Return to work"[All]) and
      ("Back to work"[All]) had Recall/Precision ratio of 30.46/19.11, 59.55/87.38 and
      3.18/90.91%, respectively. Their combination with the Boolean operator OR yielded
      to a Recall/Precision ratio of 73.89/58.44% and a NNR of 1.7. For the end user
      requiring comprehensive literature search, the best string was ("Return to work"
      OR "Back to work" OR "Rehabilitation, vocational"[MeSH] OR
      "rehabilitation"[Subheading]), with a Recall of 88.22% and a NNR of 18.
      CONCLUSIONS: No single MeSH term is available to help the physician to identify
      relevant studies on RTW in Medline. Locating these types of studies requires the
      use of various MeSH and non-MeSH terms in combination to obtain a satisfactory
      Recall. Nevertheless, enhancing the Recall of search strategies may lead to lower
      Precision, and higher NNR, although with a non linear trend. This factor must be
      taken into consideration by the end user in order to improve the cost
      effectiveness ratio of the search in Medline.

PMID- 19381788
TI  - Pregnancy and breast cancer: when they collide.
AB  - Women of childbearing age experience an increased breast cancer risk associated
      with a completed pregnancy. For younger women, this increase in breast cancer
      risk is transient and within a decade after parturition a cross over effect
      results in an ultimate protective benefit. The post-partum peak of increased risk
      is greater in women with advanced maternal age. Further, their lifetime risk for
      developing breast cancer remains elevated for many years, with the cross over to
      protection occurring decades later or not at all. Breast cancers diagnosed during
      pregnancy and within a number of years post-partum are termed pregnancy
      associated or PABC. Contrary to popular belief, PABC is not a rare disease and
      could affect up to 40,000 women in 2009. The collision between pregnancy and
      breast cancer puts women in a fear-invoking paradox of their own health, their
      pregnancy, and the outcomes for both. We propose two distinct subtypes of PABC:
      breast cancer diagnosed during pregnancy and breast cancer diagnosed post-partum.
      This distinction is important because emerging epidemiologic data highlights
      worsened outcomes specific to post-partum cases. We reported that post-partum
      breast involution may be responsible for the increased metastatic potential of
      post-partum PABC. Increased awareness and detection, rationally aggressive
      treatment, and enhanced understanding of the mechanisms are imperative steps
      toward improving the prognosis for PABC. If we determine the mechanisms by which
      involution promotes metastasis of PABC, the post-partum period can be a window of
      opportunity for intervention strategies.

PMID- 19381790
TI  - Work-related musculoskeletal symptoms in surgeons.
AB  - INTRODUCTION: Surgeons are a unique group of healthcare professionals who are at
      risk for developing work-related musculoskeletal symptoms (WMS). The diversity of
      operating skills for laparoscopic and endovascular procedures impose different
      physical demands on surgeons, who also work under time pressure. The present
      study aims to examine the physical and psychosocial factors and their association
      with WMS among general surgeons in Hong Kong. METHOD: A survey was conducted
      among surgeons working in the General Surgery departments in public hospitals of
      Hong Kong. Over 500 questionnaires were mailed and 135 surgeons completed the
      survey successfully (response rate 27%). Questions included demographics,
      workload, ergonomic and psychosocial factors. The relationship of these factors
      with WMS symptoms in the past 12 months was examined. RESULTS: Results indicated
      a high prevalence rate of WMS symptoms in surgeons, mainly in the neck (82.9%),
      low back (68.1%), shoulder (57.8%) and upper back (52.6%) regions. Sustained
      static and/or awkward posture was perceived as the factor most commonly
      associated with neck symptoms by 88.9% of respondents. Logistic regression showed
      the total score for physical ergonomic factors was the most significant predictor
      for all 4 body regions of musculoskeletal symptoms, with OR of 2.028 (95%CI 1.29
      3.19) for the neck, 1.809 (1.34-2.43) for shoulder and 1.716 (1.24-2.37) for the
      lower back. Workstyle score was significantly associated with the symptom
      severity in the low back region (P = .003) but not with the other regions.
      CONCLUSION: These results confirmed a strong association of physical and
      psychosocial factors with the musculoskeletal symptoms in surgeons. There is a
      potential for such musculoskeletal symptoms to escalate in the future, with rapid
      advances and increasing application of minimally invasive surgery.

PMID- 19381791
TI  - The influence of culture on the experience and interpretation of disturbing
      dreams.

PMID- 19381792
TI  - The couple context of pregnancy and its effects on prenatal care and birth
      outcomes.
AB  - The couple context of pregnancy and newborn health is gaining importance with the
      increase in births to unmarried couples, a disproportionate number of which were
      not intended. This study investigates the association of early prenatal care,
      preterm birth, and low birth weight with the couple relationship context,
      including partners' joint intentions for the pregnancy, their marital status at
      conception, and the presence of relationship problems during pregnancy. Data are
      drawn from the first wave of the Early Childhood Longitudinal Study--Birth
      Cohort, a representative study of births in 2001. The sample is composed of
      parents residing together with their biological child at the time the child is 9
      months old, where both the mother and father completed the self-report interview
      (N = 5,788). Couple-level multivariate logistic regression models, weighted to
      account for the complex sampling design, were used in the analysis. Risk of
      inadequate prenatal care and preterm birth was increased when partners did not
      share intentions or when neither partner intended the pregnancy. Couples were at
      additional risk of inadequate prenatal care when the pregnancy was conceived
      nonmaritally and when the mother did not tell the father about the pregnancy,
      particularly when neither partner intended the pregnancy. The risk of premature
      birth was particularly high when the partners were unmarried and either or both
      did not intend the pregnancy. The couple context of pregnancy is important for a
      healthy pregnancy and birth. When the partner is present, practitioners and
      programs should maintain a focus on the couple, and researchers should make every
      effort to include the father's own perspective.

PMID- 19381795
TI  - Factors predicting crisis counselor referrals to other crisis counseling,
      disaster relief, and psychological services: a cross-site analysis of post
      Katrina programs.
AB  - An important aspect of crisis counseling is linking survivors with services for
      their unmet needs. We examined determinants of referrals for disaster relief,
      additional crisis counseling, and psychological services in 703,000 crisis
      counseling encounters 3-18 months after Hurricane Katrina. Referrals for disaster
      relief were predicted by clients' losses, age (adults rather than children), and
      urbanicity. Referrals for additional counseling and psychological services were
      predicted by urbanicity, losses and trauma exposure, prior trauma, and
      preexisting mental health problems. Counseling and psychological referrals
      declined over time despite continuing mental health needs. Results confirm large
      urban-rural disparities in access to services.

PMID- 19381794
TI  - A twin study of the genetics of high cognitive ability selected from 11,000 twin
      pairs in six studies from four countries.
AB  - Although much genetic research has addressed normal variation in intelligence,
      little is known about the etiology of high cognitive abilities. Using data from
      11,000 twin pairs (age range = 6-71 years) from the genetics of high cognitive
      abilities consortium, we investigated the genetic and environmental etiologies of
      high general cognitive ability (g). Age-appropriate psychometric cognitive tests
      were administered to the twins and used to create g scores standardized within
      each study. Liability-threshold model fitting was used to estimate genetic and
      environmental parameters for the top 15% of the distribution of g. Genetic
      influence for high g was substantial (0.50, with a 95% confidence interval of
      0.41-0.60). Shared environmental influences were moderate (0.28, 0.19-0.37). We
      conclude that genetic variation contributes substantially to high g in Australia,
      the Netherlands, the United Kingdom and the United States.

PMID- 19381796
TI  - Academic/State/Federal collaborations and the improvement of practices in
      disaster mental health services and evaluation.
AB  - Academic, state, and federal agencies collaborated over the last 9 years to
      improve disaster mental health services and evaluation. This process, which
      included literature reviews, a number of expert panels, and case studies, is
      described. The products resulting from this process have included the development
      of a systematic cross-site evaluation of the federally funded crisis counseling
      program and field guides for interventions aimed at providing services to
      distressed individuals in the immediate aftermath of disasters and to individuals
      needing resilience skills training weeks or months after the event. Future
      improvement of disaster mental health services calls for continued research,
      evaluation, training, and intervention development.

PMID- 19381793
TI  - Global visual processing and self-rated autistic-like traits.
AB  - The current research investigated, firstly, whether individuals with high levels
      of mild autistic-like traits display a similar profile of embedded figures test
      (EFT) and global motion performance to that seen in autism. Secondly, whether
      differences in EFT performance are related to enhanced local processing or
      reduced global processing in the ventral visual stream was also examined. Results
      indicated that people who scored high on the Autism-spectrum Quotient (AQ) were
      faster to identify embedded figures, and had poorer global motion and global form
      thresholds than low AQ scorers. However, the two groups did not differ on a task
      assessing lower-level input to the ventral stream. Overall the results indicate
      that individuals with high levels of autistic-like traits have difficulties with
      global integration in the visual pathways, which may at least partly explain
      their superior EFT performance.

PMID- 19381797
TI  - Building Xperience: a multilevel alcohol and drug prevention intervention.
AB  - "Xperience" is an innovative alcohol and drug prevention program that has adopted
      a multilevel, community-based strategy to promote drug-and-alcohol free social
      activities, venues and norms among urban youth ages 14-20. The intervention aims
      to strengthen protective factors and reduce risk factors for alcohol and other
      substance use among high school age youth by addressing multiple factors at the
      individual, peer, community and city level. The purpose of this paper is to
      discuss the process of building the different levels of this intervention during
      the 3-year formative phase. We will explain: (1) Why we chose to adopt a
      multilevel and participatory strategy, (2) Formative research leading to the
      intervention model, (3) The theoretical framework underlying the methodology, (4)
      Pilot intervention development (Years One and Two), (5) Current program methods
      and outcome goals, and lastly, (6) Some of the lessons learned, goals achieved,
      and plans for the future. This descriptive account of building a multilevel
      intervention aims to serve as a useful guide for others wishing to develop
      similar approaches, and for theorizing about some of the common challenges
      involved in this process.

PMID- 19381798
TI  - Grape seed extract acting on astrocytes reveals neuronal protection against
      oxidative stress via interleukin-6-mediated mechanisms.
AB  - Grape polyphenols are known to protect neurons against oxidative stress. We used
      grape seed extract (GSE) from "Koshu" grapes (Vitis vinifera) containing a
      variety of polyphenols, and performed transcriptome analysis to determine the
      effects of GSE on primary cultures of astrocytes in the hippocampus. GSE
      upregulated various mRNAs for cytokines, among which interleukin-6 (IL-6) showed
      the biggest increase after treatment with GSE. The GSE-evoked increase in IL-6
      mRNAs was confirmed by quantitative RT-PCR. We also detected IL-6 proteins by
      ELISA in the supernatant of GSE-treated astrocytes. We made an oxidative stress
      induced neuronal cell death model in vitro using a neuron rich culture of the
      hippocampus. Treatment of the neurons with H(2)O(2) caused neuronal cell death in
      a time- and concentration-dependent manner. Exogenously applied IL-6 protected
      against the H(2)O(2)-induced neuronal cell death, which was mimicked by
      endogenous IL-6 produced by GSE-treated astrocytes. Taken together, GSE acting on
      astrocytes increased IL-6 production, which functions as a neuroprotective
      paracrine, could protect neuronal cells from death by oxidative stress.

PMID- 19381799
TI  - Chronic exposure to high levels of zinc or copper has little effect on brain
      metal homeostasis or Abeta accumulation in transgenic APP-C100 mice.
AB  - Aberrant metal homeostasis may enhance the formation of reactive oxygen species
      and Abeta oligomerization and may therefore be a contributing factor in
      Alzheimer's disease. This study investigated the effect of chronic high intake of
      dietary Zn or Cu on brain metal levels and the accumulation and solubility of
      Abeta in vivo, using a transgenic mouse model that over expresses the C-terminal
      containing Abeta fragment of human amyloid precursor protein but does not develop
      amyloid deposits. Exposure to chronic high Zn or Cu in the drinking water
      resulted in only slight elevations of the respective metals in the brain. Total
      Abeta levels were unchanged although soluble Abeta levels were slightly
      decreased, without visible plaque formation, enhanced gliosis, antioxidant
      upregulation or neuronal loss. This study indicates that brain metal levels are
      only marginally altered by long term oral exposure to extremely high Cu or Zn
      levels, and that this does not induce Abeta-amyloid formation in human Abeta
      expressing, amyloid-free mice, although this is sufficient to modulate Abeta
      solubility in vivo.

PMID- 19381800
TI  - Personality symptoms and self-esteem as correlates of psychopathology in child
      psychiatric patients: evaluating multiple informant data.
AB  - Research on adulthood posits personality and self-esteem as important predictors
      of psychopathology. In childhood, however, the study of these relationships is
      complicated by the lack of consensus on how to combine data from multiple
      informants of child behavior. This study evaluates the relationships among
      personality symptoms, self-esteem and psychopathology in 60 child psychiatric
      patients (M (age) = 10.6) using principal component analysis (PCA) to aggregate
      data from multiple informants and compares this strategy with a single informant
      approach. When predictor and criterion measures were rated by a single informant,
      strong and differential relationships between personality symptoms, self-esteem
      and psychopathology are found. When multiple informant data were combined into
      composite scores by PCA, correlations decreased but remained significant.
      Hierarchical regression analyses affirm the robustness of the following pattern:
      Emotional Instability, Introversion and Global Self-Esteem are associated with
      internalizing whereas Disagreeableness and Behavioral Conduct primarily relate to
      externalizing problems.

PMID- 19381801
TI  - Mutations in the mitochondrial DNA D-loop region and breast cancer risk.
AB  - Mitochondrial genome alterations have been suggested to play an important role in
      carcinogenesis. The D-loop region of mitochondrial DNA (mtDNA) contains essential
      transcription and replication elements, and mutations in this region may serve as
      a potential sensor for cellular DNA damage and a marker for cancer development.
      Using data and samples from the Shanghai Breast Cancer Study, we investigated
      MnlI restriction sites located between nucleotides 16,106 and 16,437 of the mtDNA
      D-loop region to evaluate restriction fragment length polymorphism (RFLP)
      patterns in tumor tissue from 501 primary breast cancer patients when compared
      with tumor tissue from 203 women with benign breast disease (BBD). RFLP patterns
      in correspondingly paired, adjacent, non-tumor tissues taken from 120 primary
      breast cancer patients and 59 BBD controls were also evaluated. Five common RFLP
      patterns were observed, and no significant differences were observed in the
      distribution of these patterns between tumor and adjacent non-tumor tissue
      samples from breast cancer patients and tissue samples from BBD controls. On the
      other hand, somatic MnlI site mutations, defined as a difference in MnlI RFLP
      pattern between tumor tissue and the corresponding, adjacent, non-tumor tissue,
      occurred more frequently in breast cancer patients (28.3%) than in BBD patients
      (15.3%) (P = 0.05) and more frequently in proliferative BBD (13.0%) than in non
      proliferative BBD (7.1%). Our data suggest that somatic MnlI site mutations may
      play a role in the pathogenesis of breast cancer.

PMID- 19381802
TI  - Interaction of arylsulfatase-A (ASA) with its natural sulfoglycolipid substrates:
      a computational and site-directed mutagenesis study.
AB  - Arylsulfatase A (ASA) hydrolyzes sulfate esters with a pH optimum of 5.
      Interactions between p-nitrocatechol sulfate (NCS, artificial substrate) and
      active site residues of ASA are revealed from their co-crystal structure. Since
      equivalent ASA interactions with its natural substrates, sulfogalactosylceramide
      (SGC) and sulfogalactosylglycerolipid (SGG), are not known, we computationally
      docked SGC/SGG to the ASA crystal structure. Our dockings suggested that Cys69
      was the active site residue, and Lys302 & Lys123 as residues anchoring the
      sulfate group of SGC/SGG to the active site, as observed for NCS. We further
      confirmed these results using 2 recombinant ASA mutants: C69A and CKK (Cys69,
      Lys302 and Lys123-all mutated to Ala). Both ASA mutants failed to desulfate
      SGC/SGG, and CKK showed minimal binding to [(14)C]SGC, although C69A still had
      affinity for this sulfoglycolipid. However, our dockings suggested additional
      intermolecular hydrogen bonding and hydrophobic interactions between ASA and
      SGC/SGG, thus contributing to the specificity of SGC/SGG as natural substrates.

PMID- 19381803
TI  - Salicylic acid alleviates NaCl-induced changes in the metabolism of Matricaria
      chamomilla plants.
AB  - Influence of 100 mM NaCl and 50 microM salicylic acid (SA) and their combination
      on the metabolism of chamomile (Matricaria chamomilla) during 7 days was studied.
      NaCl reduced growth and selected physiological parameters and SA in combined
      treatment (NaCl + SA) reversed majority of these symptoms. Application of SA
      reduced NaCl-induced increase of Na+ in the rosettes, but not in the roots.
      Accumulation of total amino acids was stimulated in NaCl-treated roots,
      especially due to exceptional increase of proline (4.4-fold). Among phenolic
      acids, accumulation of protocatechuic acid was the most enhanced in NaCl-exposed
      leaf rosettes (ca. 3-fold) while chlorogenic and caffeic acids in the roots (2.4-
      and 2.8-fold, respectively). Total soluble phenols increased after NaCl and SA
      treatments, but root lignin content was not affected. Activity of phenylalanine
      ammonia-lyase and shikimate dehydrogenase increased in response to NaCl, but
      cinnamyl alcohol dehydrogenase was not affected and polyphenol oxidase decreased.
      Stress parameters were elevated by NaCl treatment (superoxide radical and
      malondialdehyde content, activities of catalase, ascorbate- and guaiacol
      peroxidase) and substantially prevented by SA, while accumulation of hydrogen
      peroxide decreased. Overall, SA showed strong beneficial properties against NaCl
      induced negative symptoms. Protective effect of SA was the most visible at the
      level of guaiacol-peroxidase and through amelioration of stress parameters and
      mineral nutrient contents.

PMID- 19381804
TI  - Pore structure of the Cys-loop ligand-gated ion channels.
AB  - The Cys-loop receptor family of ligand-gated ion channels (LGICs) play a key role
      in synaptic transmission in the central nervous system of animals. Recent
      advances have led to the elucidation of two crystal structures of related
      prokaryotic LGICs and the electron micrograph derived structure of the
      acetylcholine receptor from Torpedo marmorata. Here, we review the structural and
      biochemical data that form our understanding of the structure of the channel
      pore. We introduce original data from the glycine receptor using the substituted
      cysteine accessibility technique and show that while the helical structure of the
      segment that surrounds the channel pore is generally agreed, the location of the
      channel gate, the pore diameter and the structure that forms the entry to the
      channel pore are likely to differ between receptors. The fundamental structural
      differences between anion and cation selective receptors and how these
      differences are related to the pore structure are also considered.

PMID- 19381805
TI  - The potential role of nitric oxide synthase in survival and regeneration of
      magnocellular neurons of hypothalamo-neurohypophyseal system.
AB  - Previous investigations from this laboratory have demonstrated that
      hypophysectomy induces up-regulation of neuronal nitric oxide synthase (nNOS) in
      magnocellular neurons of the mammalian hypothalamo-neurohypophyseal system (HNS).
      Accompanied by this upregulation of nNOS, both neuronal regeneration and
      degeneration are also observed in this system following hypophysectomy. The
      specific aim of this study was to determine the potential role of nNOS
      upregulation in neuronal survival and regeneration after hypophysectomy in the
      adult Sprague-Dawley (SD) rat by using a competitive nitric oxide synthase
      blocker, N(G)-nitrol-L: -arginine methyl ester (L: -NAME). We found that L: -NAME
      treatment effectively blocked the regeneration of magnocellular neurons of the
      rodent hypothalamus as observed in the lumen of the third cerebral ventricle
      following hypophysectomy. However, L: -NAME had no effect on the survival of
      magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei
      after hypophysectomy. These results suggest that the induced increase of nNOS
      expression enhance the regenerative ability of magnocellular neurons of the HNS
      following hypophysectomy.

PMID- 19381806
TI  - An evaluation of the cuffless blood pressure estimation based on pulse transit
      time technique: a half year study on normotensive subjects.
AB  - In the present study, we investigated the relationship between blood pressure
      (BP) and pulse transit time (PTT) and evaluated the accuracy of the PTT-based
      cuffless BP estimation on 14 normotensive subjects. Least-squares regression was
      used to estimate BP in the first test and a repeatability test carried out half
      year later. BP in the repeatability test was also estimated using the regression
      coefficients in the first test. The results illustrated that in the first and
      repeatability tests (1) arterial BP increased and PTT decreased acutely after the
      exercises and (2) systolic BP was highly correlated with PTT. In the
      repeatability test, the estimation differences from the references were 0.0 +/-
      5.3 mmHg and 0.0 +/- 2.9 mmHg for systolic and diastolic BPs respectively using
      least-squares regression. However, the estimation differences increased to 1.4 +/
      10.2 mmHg and 2.1 +/- 7.3 mmHg for systolic and diastolic BPs, respectively when
      the regression coefficients in the first test were used for prediction. In
      summary, reasonable BP estimations were given in the first and repeatability
      tests but not using the regression coefficients obtained 6 months ago for some
      subjects.

PMID- 19381807
TI  - Month of birth, a risk factor for violent behaviour in suicidal patients admitted
      in emergency?
AB  - Although there are numerous publications on the existing link between month of
      birth and suicide, only two studies focus on suicide attempts and auto-aggressive
      behavior. Research data suggest that month of birth is related to a variation of
      5-HIAA in the cerebrospinal fluid, which correlates with violent behavior (VB).
      Therefore, the aim of this study is to search, for the first time, for a possible
      link between month of birth and the occurrence of VB in emergency, for patients
      admitted for a suicide attempt with medication. This is a 10 months prospective
      study among all the patients of the canton of Geneva, Switzerland, admitted in
      emergency for a suicide attempt with medication. During a 10 months study period
      we included 493 patients, of which 77 (15.62%) presented VB. Higher incidence of
      VB was found in subjects where born at the end of winter and the beginning of
      spring, with a maximum for April and a minimum for December. In spite of a
      relatively small number of subjects, it seems promising to study the occurrence
      of VB as a function of month of birth in patients admitted in emergency for a
      suicide attempt.

PMID- 19381808
TI  - Relationship between neighborhood context, family management practices and
      alcohol use among urban, multi-ethnic, young adolescents.
AB  - We examined relationships between alcohol-related neighborhood context,
      protective home and family management practices, and alcohol use among urban,
      racial/ethnic minority, adolescents. The sample comprised 5,655 youth who were
      primarily low SES (72%), African American (43%) and Hispanic (29%). Participants
      completed surveys in 2002-2005 (ages 11-14 years). Items assessed alcohol use,
      accessibility of alcohol at home and parental family management practices.
      Neighborhood context measures included: (1) alcohol outlet density; (2)
      commercial alcohol accessibility; (3) alcohol advertisement exposure; and (4)
      perceived neighborhood strength, reported by parents and community leaders.
      Structural equation modeling was used to assess direct and indirect relationships
      between alcohol-related neighborhood context at baseline, home alcohol access and
      family management practices in seventh grade, and alcohol use in eighth grade.
      Neighborhood strength was negatively associated with alcohol use (beta = -0.078,
      p < or = 0.05) and exposure to alcohol advertisements was positively associated
      with alcohol use (beta = 0.043, p < or = 0.05). Neighborhood strength and
      commercial alcohol access were associated with home alcohol access (beta = 0.050,
      p </= 0.05 and beta = -0.150, p < or = 0.001, respectively) and family management
      practices (beta = -0.061, p < or = 0.01 and beta = 0.083, p < or = 0.001,
      respectively). Home alcohol access showed a positive association with alcohol use
      (beta = 0.401, p < or = 0.001). Tests for indirect effects suggest that home
      alcohol access may partially mediate the relationship between neighborhood
      strength and alcohol use (beta = 0.025, p < 0.062). Results suggest inner-city
      parents respond to environmental risk, such that as neighborhood risk increases,
      so also do protective home and family management practices. Parent engagement in
      restricting alcohol access and improving family management practices may be key
      to preventive efforts to reduce alcohol use.

PMID- 19381809
TI  - Enhancing coparenting, parenting, and child self-regulation: effects of family
      foundations 1 year after birth.
AB  - This study investigated whether a psycho-educational program with modest dosage
      (eight sessions), delivered in a universal framework through childbirth education
      programs and targeting the coparenting relationship would have a positive impact
      on observed family interaction and child behavior at 6-month follow-up (child age
      1 year). One hundred sixty-nine couples, randomized to intervention and control
      conditions, participated in videotaped family observation tasks at pretest
      (during pregnancy) and at child age 1 year (2003-2007). Coparenting, parenting,
      couple relationship, and child self-regulatory behaviors were coded by teams of
      raters. Intent-to-treat analyses of program effects controlled for age,
      education, and social desirability. Evidence of significant (p < 0.05) program
      effects at follow-up emerged in all four domains. Effect sizes ranged from 0.28
      to 1.01. Targeting the coparenting relationship at the transition to parenthood
      represents an effective, non-stigmatizing means of promoting parenting quality
      and child adjustment.

PMID- 19381810
TI  - In vitro, time-resolved PIV comparison of the effect of stent design on wall
      shear stress.
AB  - The effect of stent design on wall shear stress (WSS) and oscillatory shear index
      (OSI) was studied in vitro using time-resolved digital particle image velocimetry
      (DPIV). Four drug-eluting stents [XIENCE V (Abbott Vascular), TAXUS Liberte
      (Boston Scientific), Endeavor (Medtronic), and Cypher (J&J Cordis)] and a bare
      metal stent [VISION (Abbott Vascular)] were implanted into compliant vessel
      models, and the flow was measured in physiologically accurate coronary conditions
      featuring reversal and realistic offsets between pressure and flowrate. DPIV
      measurements were made at three locations under two different flow rates
      (resting: Re = 160, f = 70 bpm and exercise: Re = 300, f = 120 bpm). It was
      observed that design substantially affected the WSS experienced at the vessel
      walls. Averaged values between struts ranged from 2.05 dynes/cm(2) (Cypher) to
      8.52 dynes/cm(2) (XIENCE V) in resting conditions, and from 3.72 dynes/cm(2)
      (Cypher) to 14.66 dynes/cm(2) (VISION) for the exercise state. Within the stent,
      the WSS dropped and the OSI increased immediately distal to each strut. In
      addition, an inverse correlation between average WSS and OSI existed. Comparisons
      with recently published results from animal studies show strong correlation
      between the measured WSS and observed endothelial cell coverage. These results
      suggest the importance of stent design on the WSS experienced by endothelial
      cells in coronary arteries.

PMID- 19381811
TI  - The mandibular cartilage metabolism is altered by damaged subchondral bone from
      traumatic impact loading.
AB  - Osteoarthritis (OA) in the temporomandibular joint (TMJ) is a degenerative
      disease caused by excessive external loading. Recently, it was reported that the
      damage in the mineralized subchondral bone caused by traumatic impact-loading is
      responsible for the initiation and progression of cartilage degeneration. Thus
      far, we have hypothesized that cytokines released from damaged subchondral bone
      from impact-loading affect the cartilage catabolism under pathological
      conditions. An impactor of 200 gw was dropped onto the top of a porcine
      mandibular condyle. After organ culture for 2 days, we investigated the
      association between the subchondral bone and cartilage using histological and
      biochemical experiments. The impact-loading induced the expression of IL-1beta
      immunohistochemically and prominently up-regulated IL-1alpha and IL-1beta mRNA
      levels in subchondral bone. We confirmed a significant decrease in type II
      collagen and aggrecan mRNA expressions in chondrocytes by co-culture with
      osteoblasts after impact-loading, and significant increase in mRNA and protein
      expressions of IL-1beta in subchondral osteoblasts from impact-loaded subchondral
      bone. The mRNA expressions of type II collagen, aggrecan, and type X collagen in
      chondrocytes were decreased significantly by the co-culture with osteoblasts pre
      treated by IL-1beta, -6, and TNF-alpha. Among them, osteoblasts pre-treated by IL
      1beta affected chondrocytes most strongly. It was also shown that IL-1beta
      treated osteoblasts enhanced the MMP-1 mRNA level most markedly in chondrocytes
      among the four cytokines. These results suggest that the TMJ subjected to impact
      loading can increase directly IL-1beta synthesis in the subchondral region,
      subsequently altering the metabolism of adjacent cartilage and may eventually
      resulting in the onset and progression of TMJ-OA.

PMID- 19381812
TI  - Investigating the role of ischemia vs. elevated hydrostatic pressure associated
      with acute obstructive uropathy.
AB  - Obstructive uropathy can cause irreversible renal damage. It has been
      hypothesized that elevated hydrostatic pressure within renal tubules and/or renal
      ischemia contributes to cellular injury following obstruction. However, these
      assaults are essentially impossible to isolate in vivo. Therefore, we developed a
      novel pressure system to evaluate the isolated and coordinated effects of
      elevated hydrostatic pressure and ischemic insults on renal cells in vitro. Cells
      were subjected to: (1) elevated hydrostatic pressure (80 cm H(2)O); (2) ischemic
      insults (hypoxia (0% O(2)), hypercapnia (20% CO(2)), and 0 mM glucose media); and
      (3) elevated pressure + ischemic insults. Cellular responses including cell
      density, lactate dehydrogenase (LDH) release, and intracellular LDH (LDH(i)),
      were recorded after 24 h of insult and following recovery. Data were analyzed to
      assess the primary effects of ischemic insults and elevated pressure. Unlike
      pressure, ischemic insults exerted a primary effect on nearly all response
      measurements. We also evaluated the data for insult interactions and identified
      significant interactions between ischemic insults and pressure. Altogether,
      findings indicate that pressure may sub-lethally effect cells and alter cellular
      metabolism (LDH(i)) and membrane properties. Results suggest that renal ischemia
      may be the primary, but not the sole, cause of cellular injury induced by
      obstructive uropathy.

PMID- 19381813
TI  - Non-invasive biomechanical evaluation of implanted human cryopreserved arterial
      homografts: comparison with pre-implanted cryografts and arteries from human
      donors and recipients.
AB  - Native vessels-grafts biomechanical mismatch (BM) is related to graft failure.
      The BM could be reduced using human cryopreserved/defrosted arteries
      (cryografts), but post-thaw cryografts' recovery could be associated with an
      impaired biomechanical behavior. In vitro, we demonstrated that our
      cryopreservation methods do not affect arteries' biomechanics, but only post
      implant studies would allow determining the cryografts' biomechanical
      performance. AIM: To characterize the biomechanical properties of implanted
      cryografts, and to compare them with cryografts pre-implant, recipients' native
      arteries, and arteries from subjects with characteristics similar to those of the
      recipients and multiorgan donors (MOD) whose arteries were cryopreserved.
      METHODS: Native femoral arteries anastomosed to cryografts, implanted cryografts,
      and arteries from subjects, recipient-like and MOD-like, were studied. In vitro
      (pre-implant cryografts) and in vivo non-invasive studies were performed.
      Arterial pressure, diameter, and wall thickness were obtained to quantify local
      and regional biomechanical parameters, and to evaluate the arterial remodeling.
      CONCLUSION: Implanted cryografts were remodeled, with an increased wall
      thickness, wall-to-lumen ratio, and wall cross-sectional area. The proximal
      distal gradual transition in stiffness remained unchanged. Implanted cryografts
      were stiffer than MOD-like arteries, but more compliant than recipients'
      arteries. The cryografts-native arteries biomechanical differences were lesser
      than those described for venous grafts or expanded polytetrafluoroethylene.

PMID- 19381814
TI  - Acculturation, discrimination, and depressive symptoms among Chinese American
      adolescents: a longitudinal study.
AB  - This study focused on the perceptions of discrimination for Chinese American
      adolescents: how perceptions changed over time, how generational status and
      acculturation were related to these changes, and whether earlier discrimination
      experiences were related to subsequent depressive symptomatology. The sample
      included 309 Chinese American adolescents who participated in a 2 year, three
      wave longitudinal study. Findings suggest that perceptions of discrimination
      became more acute over time for the majority of Chinese American adolescents in
      our study, that greater initial levels of perceptions of discrimination predicted
      a slower orientation to U.S. culture, that discrimination was not related to
      orientation to Chinese culture, and that an increase in perceptions of
      discrimination was associated with an increase in depressive symptoms. Greater
      orientation to Chinese culture was also related to fewer depressive symptoms. The
      findings are discussed in light of the unique cultural context of the study.

PMID- 19381815
TI  - High-throughput microfluidic system for monitoring diffusion-based monolayer
      yeast cell culture over long time periods.
AB  - We present a simple and high-throughput microfluidic system for diffusion-based
      monolayer yeast cell culture monitoring. Yeast cells are patterned into the micro
      cavity array with a suitable height (4 MUm) that keeps the cells fixed in
      monolayer during the cell division. Different sizes of cavities and different
      repeating times of injection were tested in order to realize as many single
      cell/cavity as possible. Single-cell/cavity has been achieved in about 40% of 100
      parallel cavities. As a demonstration, we apply this technology to investigate
      budding yeast and fission yeast cultures and show that it permits single-cell
      resolution over many cellular generations. Our results show that the technique
      provides an easy way to study the phenotype of single yeast cell cycle or cell
      cell communication in high-throughput microfluidic system.

PMID- 19381816
TI  - Quantifying tumor-selective radiation dose enhancements using gold nanoparticles:
      a monte carlo simulation study.
AB  - Gold nanoparticles can enhance the biological effective dose of radiation
      delivered to tumors, but few data exist to quantify this effect. The purpose of
      this project was to build a Monte Carlo simulation model to study the degree of
      dose enhancement achievable with gold nanoparticles. A Monte Carlo simulation
      model was first built using Geant4 code. An Ir-192 brachytherapy source in a
      water phantom was simulated and the calculation model was first validated against
      previously published data. We then introduced up to 10(13) gold nanospheres per
      cm(3) into the water phantom and examined their dose enhancement effect. We
      compared this enhancement against a gold-water mixture model that has been
      previously used to attempt to quantify nanoparticle dose enhancement. In our
      benchmark test, dose-rate constant, radial dose function, and two-dimensional
      anisotropy function calculated with our model were within 2% of those reported
      previously. Using our simulation model we found that the radiation dose was
      enhanced up to 60% with 10(13) gold nanospheres per cm(3) (9.6% by weight) in a
      water phantom selectively around the nanospheres. The comparison study indicated
      that our model more accurately calculated the dose enhancement effect and that
      previous methodologies overestimated the dose enhancement up to 16%. Monte Carlo
      calculations demonstrate that biologically-relevant radiation dose enhancement
      can be achieved with the use of gold nanospheres. Selective tumor labeling with
      gold nanospheres may be a strategy for clinically enhancing radiation effects.

PMID- 19381817
TI  - Brain and optic chiasmal herniations into sella after cabergoline therapy of
      giant prolactinoma.
AB  - Optic chiasmal herniation following dopamine agonist therapy is a rare
      complication in patients with giant prolactinomas. But there are a few case
      reports of brain and chiasmal herniation following medical therapy in such cases.
      We report a young man who developed secondary visual loss and seizures after 6
      months of medical treatment with cabergoline for giant prolactinoma. Magnetic
      resonance imaging of hypothalamic pituitary region revealed optic chiasmal and
      frontal lobe herniation into sella. There was marginal improvement in his vision
      after cabergoline dose reduction. The present case report highlights frontal lobe
      herniation in conjunction with optic chiasmal herniation as a very rare
      complication of medical therapy of giant prolactinoma. Different treatment
      options of this condition are being discussed.

PMID- 19381818
TI  - US hospitalizations and costs for illicit drug users with soft tissue infections.
AB  - Skin and soft tissue infections (SSTIs) are common complications of illicit drug
      use. Studies at single, urban hospitals demonstrate high rates of emergency
      department visits and hospitalizations for these infections. This study sought to
      estimate nationwide and regional incidence and costs of hospitalizations for
      illicit drug users with SSTIs in the US. AHRQ's Nationwide Inpatient Sample was
      used to conduct a retrospective cross-sectional, time-series study.
      Hospitalizations of illicit drug users with SSTIs were identified using
      International Classification of Diseases, 9th Revision Clinical Modification
      codes. An estimated 106,126 hospitalizations for illicit drug users with SSTIs
      represented 0.07% of all US non-Federal hospitalizations from 1998 to 2001 and
      cost over 193 million dollars in 2001. Higher rates of hospitalization were found
      in the West, Northeast, and urban teaching hospitals. Hospitalization rates for
      illicit drug users with SSTIs vary significantly according to US region.
      Resources to reduce the incidence and severity of these infections should be
      targeted accordingly.

PMID- 19381819
TI  - Low-grade gliomas.
AB  - Low-grade gliomas (LGG) are uncommon central nervous system (CNS) tumors which
      often present with seizures and few other neurologic signs or symptoms.
      Multimodality therapy encompassing surgical resection, radiation therapy (RT),
      and chemotherapy may provide the best disease-free and overall survival (OS).
      Each of these treatment modalities plays an important role in the treatment of
      these tumors. The understanding and management of LGG is evolving as randomized
      clinical trials have begun to address many questions related to the timing and
      order of each of the available treatments and their individual and combined
      effects on progression-free survival (PFS) and OS. Currently, an attempt at
      surgical resection followed by external beam RT is a typical treatment approach,
      at least in high-risk patients. Observation with serial brain imaging studies or
      surgical resection or debulking alone may be acceptable options in patients with
      low-risk tumors. The role of chemotherapy in either group is less clear, but
      recent studies have indicated that concurrent chemotherapy with radiation
      improves PFS and may eventually impact OS. The European Organization for Research
      and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG)
      are currently conducting two large Phase III and Phase II studies, respectively.
      The studies seek to evaluate the efficacy of radiotherapy and either temozolomide
      or a combination of procarbazine, vincristine, and lomustine in high-risk LGG
      patients. Ongoing investigative efforts seek to confirm the predictive value of a
      number of molecular markers including the loss of chromosomes 1p and 19q and the
      epigenetic silencing of the methylguanine-DNA methyltransferase (MGMT) gene.
      Additional smaller clinical trials seek to establish the role of newer targeted
      therapies including small-molecule tyrosine kinase inhibitors in patients with
      newly diagnosed and recurrent LGG.

PMID- 19381820
TI  - The role of chemotherapy for pure and mixed anaplastic oligodendroglial tumors.
AB  - Pure and mixed anaplastic oligodendrogliomas (AO/mixed-AOs) remain terminal
      primary brain tumors, without a defined optimal initial therapy, and without
      sufficiently active and tolerable therapies at recurrence/progression (R/P). Very
      heterogeneous international therapy recommendations remain. Historical advances
      have resulted in only modest improvements in outcome. AO/mixed-AOs with 1p/19q co
      deletion are prognostically favorable, regardless of therapy, and must be
      identified as early as possible. Following resection, outcome data on initial
      therapy with radiation (RT) remain the most mature, although controversies
      regarding its true toxicities and optimal timing continue. Recently, the landmark
      RTOG 9402 and EORTC 26951 trials showed that the addition of Procarbazine, CCNU,
      Vincristine chemotherapy to RT, at anytime during initial therapy, prolongs
      progression-free survival, but not survival, and not without moderate toxicity.
      Despite a lack of definitive evidence, this strategy has commonly been
      extrapolated to Temozolomide. Chemo-sensitivity of AO/mixed-AOs provides the
      rationale for the chemotherapy-only strategies being explored. In the setting of
      recurrence/progression (R/P), chemotherapy, small molecule (targeted), biologic,
      and other strategies have been relatively disappointing, toxic, and cumbersome.
      Partly secondary to biases regarding the relative toxicities of tumor burden vs.
      treatment effect, therapy remains highly individualized. Future international
      research must prospectively evaluate health-related quality of life, toxicity,
      and molecular genetic markers.

PMID- 19381821
TI  - Treatment of advanced thymoma and thymic carcinoma.
AB  - Although thymic epithelial tumors are rare, they are relatively common among
      neoplasms of the anterior superior mediastinum. They usually exhibit indolent
      behavior, but do have the capacity to invade surrounding structures and
      metastasize to distant sites. Thymic carcinomas are rare, but are highly
      aggressive tumors that are associated with a poor prognosis. The mainstay of
      therapy is complete surgical resection. Locally advanced thymoma and thymic
      carcinoma require a multimodality treatment approach with a combination of
      surgery, chemotherapy, and radiation therapy to decrease the chances of
      recurrence and improve survival. The risk of disease recurrence lasts for a
      number of years after completion of primary therapy. A majority of cases of
      recurrent disease present as pleural recurrences. Once again, surgical resection
      of recurrent disease represents the cornerstone of successful therapy and is
      critical to long-term survival. In recent years, a better understanding of the
      biologic basis of thymic epithelial tumors has led to the emergence of targeted
      therapy directed against this malignancy.

PMID- 19381822
TI  - Current status on biologic therapies in the treatment of epithelial ovarian
      cancer.
AB  - Treatment of epithelial ovarian cancer generally involves surgical staging
      followed by chemotherapy with a combination of a platinum and a taxane-containing
      agent. However, a majority of patients recur and ultimately succumb to their
      cancer. Novel therapies that target specific pathways involved in ovarian
      tumorigenesis are rapidly emerging. In ovarian cancer, targeted therapies have
      focused on both the vascular endothelial growth factor (VEGF) and epidermal
      growth factor receptor (EGFR) pathways. Single-agent bevacizumab, a VEGF
      inhibitor, demonstrated significant clinical activity in multiple phase II
      studies. Various combinations of cytotoxic and biologic agents with bevacizumab
      as well as newer anti-angiogenesis agents are being tested. In contrast, EGFR
      inhibitors have not shared the same clinical activity in epithelial ovarian
      cancers as compared to the VEGF inhibitors. Translational studies are needed to
      help design rational combinations of targeted agents and to help predict response
      to therapy.

PMID- 19381823
TI  - Effect of sugars, surfactant, and tangential flow filtration on the freeze-drying
      of poly(lactic acid) nanoparticles.
AB  - Poly(D,L-lactic acid) nanoparticles were freeze-dried in this study. With respect
      to drying, effect of protective excipients and purification from excess
      surfactant were evaluated. The nanoparticles were prepared by the
      nanoprecipitation method with or without a surfactant, poloxamer 188. The
      particles with the surfactant were used as such or purified by tangential flow
      filtration. The protective excipients tested were trehalose, sucrose, lactose,
      glucose, poloxamer 188, and some of their combinations. The best freeze-drying
      results in terms of nanoparticle survival were achieved with trehalose or sucrose
      at concentrations 5% and 2% and, on the other hand, with a combination of lactose
      and glucose. Purification of the nanoparticle dispersion from the excess
      surfactant prior to the freeze-drying by tangential flow filtration ensured
      better drying outcome and enabled reduction of the amount of the protective
      excipients used in the process. The excess surfactant, if not removed, was
      assumed to interact with the protective excipients decreasing their protective
      mechanism towards the nanoparticles.

PMID- 19381824
TI  - SMEDDS of glyburide: formulation, in vitro evaluation, and stability studies.
AB  - The objective of the present investigation was to develop and evaluate self
      microemulsifying drug delivery system (SMEDDS) for improving the delivery of a
      BCS class II antidiabetic agent, glyburide (GLY). The solubility of GLY in oils,
      cosurfactants, and surfactants was evaluated to identify the components of the
      microemulsion. The ternary diagram was plotted to identify the area of
      microemulsion existence. The in vitro dissolution profile of GLY SMEDDS was
      evaluated in comparison to the marketed GLY tablet and pure drug in pH 1.2 and pH
      7.4 buffers. The chemical stability of GLY in SMEDDS was determined as per the
      International Conference on Harmonisation guidelines. The area of microemulsion
      existence increased with the increase in the cosurfactant (Transcutol P)
      concentration. The GLY microemulsion exhibited globule size of 133.5 nm and
      polydispersity index of 0.94. The stability studies indicated that GLY undergoes
      significant degradation in the developed SMEDDS. This observation was totally
      unexpected and has been noticed for the first time. Further investigations
      indicated that the rate of GLY degradation was highest in Transcutol P.

PMID- 19381825
TI  - Microemulsion-based vaginal gel of clotrimazole: formulation, in vitro
      evaluation, and stability studies.
AB  - The objective of the present investigation was to develop and evaluate
      microemulsion-based gel for the vaginal delivery of clotrimazole (CMZ). The
      solubility of CMZ in oils and surfactants was evaluated to identify components of
      the microemulsion. The ternary diagram was plotted to identify the area of
      microemulsion existence. Various gelling agents were evaluated for their
      potential to gel the CMZ microemulsion without affecting its structure. The
      bioadhesive potential and antifungal activity of the CMZ microemulsion-based gel
      (CMZ-MBG) was determined in comparison to the marketed clotrimazole gel (Candid-V
      gel) by in vitro methods. The chemical stability of CMZ in CMZ-MBG was determined
      as per the International Conference on Harmonization guidelines. The CMZ
      microemulsion exhibited globule size of 48.4 nm and polydispersity index of 0.75.
      Carbopol ETD 2020 could successfully gel the CMZ microemulsion without disturbing
      the structure. The CMZ-MBG showed significantly higher (P < 0.05) in vitro
      bioadhesion and antifungal activity as compared to that of Candid-V gel. The
      stability studies indicated that CMZ undergoes acidic pH-catalyzed degradation at
      all the storage conditions at the end of 3 months.

PMID- 19381826
TI  - Influence of the selected antioxidants on the stability of the Celsior solution
      used for perfusion and organ preservation purposes.
AB  - The purpose of the following research was to improve the original Celsior
      solution in order to obtain a higher degree of stability and effectiveness. The
      solution was modified by the addition of selected antioxidants such as vitamin C,
      cysteine, and fumaric acid in the following concentrations: 0.1, 0.3, and 0.5
      mmol/l. The solution's stability was estimated using an accelerated stability
      test based on changes in histidine concentrations in the solution using Pauly's
      method for determining concentrations. Elevated temperatures, the factor
      accelerating substances' decomposition reaction rate, were used in the tests. The
      research was conducted at four temperatures at intervals of 10 degrees C: 60 +/-
      0.2 degrees C, 70 +/- 0.2 degrees C, 80 +/- 0.2 degrees C, and 90 +/- 0.2 degrees
      C. It was stated that the studied substances' decomposition occurred in
      accordance with the equation for first-order reactions. The function of the
      logarithmic concentration (log%C) over time was revealed to be rectilinear. This
      dependence was used to determine the kinetics of decomposition reaction rate
      parameters (the rate constant of decomposition k, activation energy E (a), and
      frequency factor A). On the basis of these parameters, the stability of the
      modified solution was estimated at +5 degrees C. The results obtained show that
      the proposed antioxidants have a significant effect on lengthening the Celsior
      solution's stability. The best results were reached when combining two
      antioxidants: vitamin C and cysteine in 0.5 mmol/l concentrations. As a result,
      the Celsior solution's stability was lengthened from 22 to 299 days, which is
      13.5 times. Vitamin C at a concentration of 0.5 mmol/l increased the solution's
      stability by 5.2 times (t(90) = 115 days), cysteine at a concentration of 0.5
      mmol/l caused a 4.4 times stability increase (t(90) = 96 days), and fumaric acid
      at a concentration of 0.5 mmol/l extended the stability by 2.1 times (t(90) = 48
      days) in relation to the original solution.

PMID- 19381827
TI  - Development and evaluation of sustained release gastroretentive minimatrices for
      effective treatment of H. pylori infection.
AB  - In the present work, sustained release gastroretentive minimatrices of
      amoxicillin have been designed and optimized using central composite design.
      Effect of amount of xanthan gum, rate controlling polymers (HPMC K100M CR/PEO
      coagulant (1:1)), carbopol 974P, and gas generating couple (sodium
      bicarbonate/citric acid (3:1)) was studied on dependent (response) variables,
      i.e., buoyancy lag time, drug release at 1 h, time required for 95% drug release,
      swelling index, and bioadhesive strength. Minimatrices were prepared by non
      aqueous granulation method using solution of PVP K30 in isopropyl alcohol. All
      the formulations were found to contain 99.2% to 100.9% of amoxicillin per
      minimatrix. Optimum formulation (Formulation number AGT09) containing high level
      of the independent variables was having buoyancy lag time of 7 min and drug
      release at 1 h was 32.5%. It required 9.39 h for 95% drug release while swelling
      index and bioadhesive strength were 341 and 17.9 dyn/cm(2), respectively. This
      formulation was said to be optimum because it has minimum buoyancy lag time,
      requires maximum time for 95% drug release, and has higher bioadhesive
      capabilities. In vitro results of an optimized formulation indicate its sustained
      drug release and gastric retention capability, which may be very useful for
      effective treatment of H. pylori infection.

PMID- 19381828
TI  - Anhydride prodrug of ibuprofen and acrylic polymers.
AB  - The objective of this study was to synthesize anhydride prodrugs for carboxylic
      acid-bearing agents such as non-steroidal anti-inflammatory drugs, shield the
      carboxylic acid group from irritative effects, and obtain sustained release
      patterns. Ibuprofen was used as a representative drug for anhydride
      derivatization. Conjugates of ibuprofen with carboxylic acid moieties of
      different acrylic polymers were prepared by dehydration reaction using acetic
      anhydride. Products were characterized by infrared spectroscopy, nuclear magnetic
      resonance, and scanning electron microscopy followed by preparation of
      microspheres with different sizes from the conjugate Eudragit L-100-ibuprofen.
      The drug release was monitored by high-performance liquid chromatography.
      Ibuprofen was bound to the polymers via an anhydride bond in high reaction yields
      (75-95%) with drug loading of up to 30% (w/w). These anhydride derivatives
      hydrolyzed and release the drug at different periods ranging from 1 to 5 days,
      depending on the hydrophobicity and the cross-linking of the conjugates. The
      release of drug from the microspheres was correlated to their size and ranged
      from 2 to almost 8 days. This study demonstrates the promise of anhydride prodrug
      for extending drug action while shielding the carboxylic acid group.

PMID- 19381829
TI  - Formulation and performance characterization of radio-sterilized "progestin-only"
      microparticles intended for contraception.
AB  - The aim of this study was to formulate and characterize a microparticulate system
      of progestin-only contraceptive. Another objective was to evaluate the effect of
      gamma radio-sterilization on in vitro and in vivo drug release characteristics.
      Levonorgestrel (LNG) microspheres were fabricated using poly(lactide-co
      glycolide) (PLGA) by a novel solvent evaporation technique. The formulation was
      optimized for drug/polymer ratio, emulsifier concentration, and process variables
      like speed of agitation and evaporation method. The drug to polymer ratio of 1:5
      gave the optimum encapsulation efficiency. Speed of agitation influenced the
      spherical shape of the microparticles, lower speeds yielding less spherical
      particles. The speed did not have a significant influence on the drug payloads. A
      combination of stabilizers viz. methyl cellulose and poly vinyl alcohol with in
      water solvent evaporation technique yielded microparticles without any free drug
      crystals on the surface. This aspect significantly eliminated the in vitro
      dissolution "burst effect". The residual solvent content was well within the
      regulatory limits. The microparticles passed the test for sterility and absence
      of pyrogens. In vitro dissolution conducted on the product before and after gamma
      radiation sterilization at 2.5 Mrad indicated no significant difference in the
      drug release patterns. The drug release followed zero-order kinetics in both
      static and agitation conditions of dissolution testing. The in vivo studies
      conducted in rabbits exhibited LNG release up to 1 month duration with drug
      levels maintained within the effective therapeutic window.

PMID- 19381830
TI  - Comparison of the halving of tablets prepared with eccentric and rotary tablet
      presses.
AB  - The aim of this study was to compare the densification of powder mixtures on
      eccentric and rotary tablet presses and to establish relationships with the
      halving properties of the resulting scored tablets. This is an important problem
      because the recent guidelines of EU require verification of the equal masses of
      tablet halves. The models of Walker, Heckel, and Kawakita were used to describe
      the powder densification on the two machines. The calculated parameters revealed
      that the shorter compression cycle of rotary machines results in poorer
      densification and lower tablet hardness at a given compression force. This is
      manifested in poorer halving properties, which are influenced mainly by the
      hardness. Better densification improves the halving even at lower tablet
      hardness. This demonstrates that these parameters can be good predictors of
      tablet halving properties.

PMID- 19381831
TI  - Development and evaluation of ethyl cellulose-based transdermal films of
      furosemide for improved in vitro skin permeation.
AB  - Transdermal films of the furosemide were developed employing ethyl cellulose and
      hydroxypropyl methylcellulose as film formers. The effect of binary mixture of
      polymers and penetration enhancers on physicochemical parameters including
      thickness, moisture content, moisture uptake, drug content, drug-polymer
      interaction, and in vitro permeation was evaluated. In vitro permeation study was
      conducted using human cadaver skin as penetration barrier in modified Keshary
      Chein diffusion cell. In vitro skin permeation study showed that binary mixture,
      ethyl cellulose (EC)/hydroxypropyl methylcellulose (HPMC), at 8.5:1.5 ratio
      provided highest flux and also penetration enhancers further enhanced the
      permeation of drug, while propylene glycol showing higher enhancing effect
      compared to dimethyl sulfoxide and isopropyl myristate. Different kinetic models,
      used to interpret the release kinetics and mechanism, indicated that release from
      all formulations followed apparent zero-order kinetics and non-Fickian diffusion
      transport except formulation without HPMC which followed Fickian diffusion
      transport. Stability studies conducted as per International Conference on
      Harmonization guidelines did not show any degradation of drug. Based on the above
      observations, it can be reasonably concluded that blend of EC-HPMC polymers and
      propylene glycol are better suited for the development of transdermal delivery
      system of furosemide.

PMID- 19381832
TI  - Colon specific delivery of indomethacin: effect of incorporating pH sensitive
      polymers in xanthan gum matrix bases.
AB  - In the present study, an attempt has been made to design controlled release colon
      specific formulations of indomethacin by employing pH responsive polymers
      Eudragit (L100 or S100) in matrix bases comprised of xanthan gum. The prepared
      tablets were found to be of acceptable quality with low-weight variation and
      uniform drug content. In vitro release studies indicated rapid swelling and
      release of significant percentage of drug in the initial period from matrix
      tablets composed of xanthan gum alone. Addition of pH responsive polymers
      Eudragit (L100 or S100) to xanthan gum matrix resulted in negligible to very low
      drug release in the initial period in acidic to weakly acidic medium.
      Furthermore, with increase in pH of the dissolution medium due to dissolution of
      Eudragit L100/Eudragit S100 that resulted in the formation of a porous matrix,
      faster but controlled drug release pattern was observed. Thus, a sigmoidal
      release pattern was observed from the designed formulations suitable for colonic
      delivery. Drug release mechanism in all cases was found to be of super case II
      type, indicating erosion to be the primary cause of drug release. Since the drug
      release from almost all the matrix bases in the initial phase was negligibly low
      and followed with controlled release for about 14-16 h, it was concluded that a
      matrix design of this composition could have potential applications as a colon
      specific drug delivery device with additional advantage of easy scale-up and
      avoidance of all-or-none phenomenon associated with coated colon-specific
      systems.

PMID- 19381833
TI  - Intratumoral delivery of Paclitaxel in solid tumor from biodegradable hyaluronan
      nanoparticle formulations.
AB  - In the current study, novel paclitaxel-loaded cross-linked hyaluronan
      nanoparticles were engineered for the local delivery of paclitaxel as a prototype
      drug for cancer therapy. The nanoparticles were prepared using a desolvation
      method with polymer cross-linking. In vitro cytotoxicity studies demonstrated
      that less than 75% of the MDA-MB-231 and ZR-75-1 breast cancer cells were viable
      after 2-day exposure to paclitaxel-loaded hyaluronan nanoparticles or free
      paclitaxel, regardless of the dose. These results suggest that hyaluronan
      nanoparticles maintain the pharmacological activity of paclitaxel and efficiently
      deliver it to the cells. Furthermore, in vivo administration of the drug-loaded
      nanoparticles via direct intratumoral injection to 7,12-dimethylbenz[a]anthracene
      (DMBA)-induced mammary tumor in female rats was studied. The paclitaxel-loaded
      nanoparticles treated group showed effective inhibition of tumor growth in all
      treated rats. Interestingly, there was one case of complete remission of tumor
      nodule and two cases of persistent reduction of tumor size that was observed on
      subsequent days. In the case of free paclitaxel-treated group, the mean tumor
      volume increased almost linearly (R(2) = 0.93) with time to a size that was 4.9
      fold larger than the baseline volume at 57 days post-drug administration.
      Intratumoral administration of paclitaxel-loaded hyaluronan nanoparticles could
      be a promising treatment modality for solid mammary tumors.

PMID- 19381834
TI  - Development of microsponges for topical delivery of mupirocin.
AB  - The goal of the present study was to develop and evaluate microsponge-based
      topical delivery system of mupirocin for sustained release and enhanced drug
      deposition in the skin. Microsponges containing mupirocin were prepared by an
      emulsion solvent diffusion method. The effect of formulation and process
      variables such as internal phase volume and stirring speed on the physical
      characteristics of microsponges were examined on optimized drug/polymer ratio by
      3(2) factorial design. The optimized microsponges were incorporated into an
      emulgel base. In vitro drug release, ex vivo drug deposition, and in vivo
      antibacterial activity of mupirocin-loaded formulations were studied. Developed
      microsponges were spherical and porous, and there was no interaction between drug
      and polymer molecules. Emulgels containing microsponges showed desired physical
      properties. Drug release through cellulose dialysis membrane showed diffusion
      controlled release pattern and drug deposition studies using rat abdominal skin
      exhibited significant retention of active in skin from microsponge-based
      formulations by 24 h. The optimized formulations were stable and nonirritant to
      skin as demonstrated by Draize patch test. Microsponges-based emulgel
      formulations showed prolonged efficacy in mouse surgical wound model infected
      with S. aureus. Mupirocin was stable in topical emulgel formulations and showed
      enhanced retention in the skin indicating better potential of the delivery system
      for treatment of primary and secondary skin infections, such as impetigo, eczema,
      and atopic dermatitis.

PMID- 19381835
TI  - Hesperidin gastroresistant microparticles by spray-drying: preparation,
      characterization, and dissolution profiles.
AB  - Gastroresistant microparticles for oral administration of hesperidin (Hd) were
      produced by spray-drying using cellulose acetate phthalate (CAP) as enteric
      polymer in different polymer/Hd weight ratio (1:1, 3:1, and 5:1), and a series of
      enhancers of the dissolution rate, such as sodium carboxymethylcellulose
      crosslinked (CMC), sodium dodecylbenzene sulfonate (SDBS), or Tween85. The raw
      materials and the microparticles were investigated by differential-scanning
      calorimetry, X-ray diffraction, infrared spectroscopy and imaged using scanning
      electron and fluorescence microscopy. In vitro dissolution tests were conducted
      using a pH-change method to investigate the influence of formulative parameters
      on the dissolution/release properties of the drug. CAP/Hd microparticles showed a
      good gastro-resistance but incomplete drug dissolution in the simulated
      intestinal fluid (SIF). The presence of the enhancers in the formulation produced
      well-formed microparticles with different size and morphology, containing the
      drug well coated by the polymer. All the enhancers were able to increase the
      dissolution rate of Hd in the simulated intestinal environment without altering
      CAP ability to protect Hd in the acidic fluid. The spray-drying technique and
      process conditions selected were effective in microencapsulating and stabilizing
      the flavonoid giving satisfactory encapsulation efficiency, product yield, and
      microparticles morphology, and a complete drug release in the intestine.

PMID- 19381836
TI  - Incorporation in lipid microparticles of the UVA filter, butyl
      methoxydibenzoylmethane combined with the UVB filter, octocrylene: effect on
      photostability.
AB  - The aim of this study was to reduce the photoinstability of butyl
      methoxydibenzoylmethane (BMDBM), the most widely used UVA filter, by
      incorporating it in lipid microparticles (LMs) alone or together with the UVB
      filter octocrylene (OCR), acting also as photostabilizer. Microparticles loaded
      with BMDBM or with combined BMDBM and OCR were produced by the hot emulsion
      technique, using glyceryl behenate as lipid material and poloxamer 188 as
      surfactant. The LMs were characterized by release studies, scanning electron
      microscopy, and powder X-ray diffractometry. The BMDBM and OCR loading was 15.2%
      and 10.6%, respectively. In order to reproduce the conditions prevalent in
      commercial sunscreen products, the photoprotective efficacy of the LMs was
      evaluated after their introduction in a model cream (oil-in-water emulsion)
      containing a mixture of UVA and UVB filters. A small but statistically
      significant decrease in BMDBM photodegradation was obtained when the UVA filter
      was encapsulated alone into the LMs (the extent of degradation was 28.6% +/-2.4
      for non-encapsulated BMDBM and 26.0% +/-2.5 for BMDBM-loaded microparticles). On
      the other hand, the co-loading of OCR in the LMs produced a more marked reduction
      in the light-induced decomposition of microencapsulated BMDBM (the UVA filter
      loss was 21.5% +/-2.2). Therefore, incorporation in lipid microparticles of BMDBM
      together with the sunscreen OCR is more effective in enhancing the UVA filter
      photostability than LMs loaded with BMDBM alone.

PMID- 19381837
TI  - The study on the entrapment efficiency and in vitro release of puerarin submicron
      emulsion.
AB  - The entrapment efficiency (EE) and release in vitro are very important
      physicochemical characteristics of puerarin submicron emulsion (SME). In this
      paper, the performance of ultrafiltration (UF), ultracentrifugation (UC), and
      microdialysis (MD) for determining the EE of SME were evaluated, respectively.
      The release study in vitro of puerarin from SME was studied by using MD and
      pressure UF technology. The EE of SME was 86.5%, 72.8%, and 55.8% as determined
      by MD, UF, and UC, respectively. MD was not suitable for EE measurements of
      puerarin submicron oil droplet, which could only determine the total EE of
      submicron oil droplet and liposomes micelles, but it could be applied to
      determine the amount of free drug in SMEs. Although UC was the fastest and
      simplest to use, its results were the least reliable. UF was still the relatively
      accurate method for EE determination of puerarin SME. The release of puerarin SME
      could be evaluated by using MD and pressure UF, but MD seemed to be more suitable
      for the release study of puerarin emulsion. The drug release from puerarin SME at
      three drug concentrations was initially rapid, but reached a plateau value within
      30 min. Drug release of puerarin from the SME occurred via burst release.

PMID- 19381838
TI  - Therapeutic paint of cidofovir/sucralfate gel combination topically administered
      by spraying for treatment of orf virus infections.
AB  - The aim of the research was to study a new cidofovir/sucralfate drug product to
      be used as a spray for treating the mucosal and/or skin lesions. The product,
      i.e., a water suspension of sucralfate (15% w/w) and cidofovir (1% w/w), combines
      the potent antiviral activity of the acyclic nucleoside phosphonate cidofovir
      ((S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) and the wound healing
      properties of sucralfate gel (sucrose octasulphate basic aluminum salt). The
      product was characterized in vitro with respect to compatibility between drug and
      carrier, spray particle size, spray deposition, drying kinetics, and drug content
      and release. An interaction between the two active substances was found. The
      interaction between sucralfate and cidofovir was counteracted by introducing
      sodium dihydrogen phosphate (16% w/w) in the preparation. The spray formulation
      containing cidofovir/sucralfate gel painted the skin and dried quickly to a scab,
      remaining firmly adhered to the lesions. The therapeutic paint was tested in vivo
      on lambs infected with orf virus by treating the animals with different
      cidofovir/sucralfate formulations (0.5% or 1% cidofovir + sucralfate 15% +
      NaH(2)PO(4) 16% w/w) and with sucralfate gel suspension alone as control. The
      treatment with formulations containing cidofovir and phosphate salt for four
      consecutive days resulted in a rapid resolution of the lesions, with scabs
      containing significantly lower amounts of viable virus when compared with
      untreated lesions and lesions treated with sucralfate suspension alone.

PMID- 19381839
TI  - Workshop report and follow-up--AAPS Workshop on current topics in GLP
      bioanalysis: Assay reproducibility for incurred samples--implications of Crystal
      City recommendations.
AB  - The Conference Report of the 3rd AAPS/FDA Bioanalytical Workshop (Crystal City
      III) endorsed the concept that assay methods supporting bioanalytical data in
      submissions must demonstrate assay reproducibility by using incurred samples. The
      present Workshop was convened to provide a forum for discussion and consensus
      building about incurred sample assay reproducibility for both nonclinical and
      clinical studies. Information about current regulatory perspectives on incurred
      sample reanalysis (ISR) was presented, implications of ISR for both large and
      small molecules were discussed, and the steering committee put forth
      recommendations for performing ISR. These recommendations from the Workshop,
      along with the subsequent evolution of approaches leading to a robust ISR
      program, may be used by scientists performing bioanalytical assays for regulated
      studies to provide additional confirmation of assay reproducibility for incurred
      samples.

PMID- 19381841
TI  - Mechanistic approaches to predicting oral drug absorption.
AB  - Modeling and simulation of oral drug absorption have been widely used in drug
      discovery, development, and regulation. Predictive absorption models are used to
      determine the rate and extent of oral drug absorption, facilitate lead drug
      candidate selection, establish formulation development strategy, and support the
      development of regulatory policies. This review highlights the development of
      recent drug absorption models including dispersion and compartmental models. The
      compartmental models include the compartmental absorption and transit model;
      Grass model; gastrointestinal transit absorption model; advanced compartmental
      absorption and transit model; and advanced dissolution, absorption, and
      metabolism model. Compared to the early absorption models, the above models
      developed or extended since the mid-1990s have demonstrated greatly improved
      predictive performance by accounting for multiple factors such as drug
      degradation, gastric emptying, intestinal transit, first-pass metabolism, and
      intestinal transport. For future model development, more heterogeneous features
      of the gastrointestinal tract (villous blood flow, metabolizing enzymes, and
      transporters), food effects, and drug-drug interactions should be fully
      characterized and taken into consideration. Moreover, predicting population inter
      and intravariability in oral drug absorption can be useful and important for the
      evaluation of clinical safety and efficacy of drugs. Establishing databases and
      libraries that contain accurate pharmaceutical and pharmacokinetic information
      for commercialized and uncommercialized drugs may also be helpful for model
      development and validation.

PMID- 19381840
TI  - Population-based mechanistic prediction of oral drug absorption.
AB  - The bioavailability of drugs from oral formulations is influenced by many
      physiological factors including gastrointestinal fluid composition, pH and
      dynamics, transit and motility, and metabolism and transport, each of which may
      vary with age, gender, race, food, and disease. Therefore, oral bioavailability,
      particularly of poorly soluble and/or poorly permeable compounds and those that
      are extensively metabolized, often exhibits a high degree of inter- and intra
      individual variability. While several models and algorithms have been developed
      to predict bioavailability in an average person, efforts to accommodate intrinsic
      variability in the component processes are less common. An approach that
      incorporates such variability for human populations within a mechanistic
      framework is described together with examples of its application to drug and
      formulation development.

PMID- 19381843
TI  - Behavior of varroa mites in worker brood cells of Africanized honey bees.
AB  - The ectoparasitic mite Varroa destructor is currently the most important pest of
      the honey bee, Apis mellifera. Because mite reproduction occurs within the sealed
      cell, the direct observation of varroa activity inside the cell is difficult. A
      video observation method using transparent polystyrol cells containing infested
      brood was used to analyze the behavior of varroa mites in worker brood of
      Africanized honey bees. We recorded how mites feed on the larva and pupa,
      construct a fecal accumulation site and how the bee larva carried out some
      longitudinal movements around the cell. The feeding activity of the foundress
      mite varies during the course of the cycle. On the prepupa mites were found to
      feed often (0.3 +/- 0.2 bouts h(-1)) for a period of 8.7 +/- 8.4 min h(-1) and
      there was no preference for a specific segment as feeding site. On the opposite,
      during the pupal stage mites fed less often (0.1 +/- 0.1 bouts h(-1)) for a
      period of 6.2 +/- 4.0 min h(-1) and almost always at a particular site (92.4%).
      On pupa, 83.7% of the feeding was on the 2nd abdominal segment (n = 92), and only
      few perforations were found on the thorax. Varroa shows a preference for
      defecation in the posterior part of the cell (cell apex), close to the bee's anal
      zone. We found a high correlation between the position of the feeding site on the
      pupa and the position of the fecal accumulation on the cell wall. Most infested
      cells have only one fecal accumulation site and it was the favorite resting site
      for the mite, where it spent 24.3 +/- 3.9 min h(-1). Longitudinal displacements
      were observed in 28.0% (n = 25) of the analyzed bee larvae. Turning movements
      around the cell, from the bottom to the top, were carried out by these larvae,
      mainly during the second day (47.7 +/- 22.5 min h(-1)), just before pupation,
      with a total time of 874.9 +/- 262.2 min day(-1) (n = 7 individuals). These
      results in worker brood of Africanized bees demonstrate adaptations of varroa
      mites to parasitizing the developing bee inside the capped brood cells.

PMID- 19381842
TI  - The Cerebrovascular Attitudes and Beliefs Scale (CABS-R): the factor structure
      and psychometric properties of a tool for assessing stroke-related health
      beliefs.
AB  - BACKGROUND: Worldwide stroke is serious problem and one that necessitates
      continued efforts towards prevention. The health belief model suggests that
      improvements in prevention will follow from incorporating strategies that change
      beliefs, but this approach relies on the availability of tools for measuring such
      change. The Cerebrovascular Attitudes and Beliefs Scale (CABS-R) was developed to
      meet this need. PURPOSE: The purpose of this study was to investigate the
      psychometric properties of the CABS-R. METHOD: In 2007, 126 Brisbane residents
      aged 50 years and older completed the CABS-R. One month later, 70 participants
      completed the CABS-R again. Internal consistency, test-retest, and exploratory
      factor analyses were performed on subscales completed by >60 participants.
      RESULTS: Analyses showed that the CABS-R has moderate-to-good internal
      consistency and that scores are relatively stable over time. A four-factor
      solution was identified, suggesting that the CABS-R validly assesses stroke
      susceptibility and seriousness and the perceived benefits of and barriers to
      exercise and weight loss for stroke prevention. CONCLUSION: This study shows that
      the CABS-R is useful to gauge changes in stroke beliefs over time. Consistent
      with the model, a four factor solution was found. The CABS-R may be a useful
      inclusion in future stroke prevention programs.

PMID- 19381844
TI  - Bacillus thuringiensis var. tenebrionis control of synanthropic mites (Acari:
      Acaridida) under laboratory conditions.
AB  - Bacillus thuringiensis (Bt) toxins present a potential for control of pest mites.
      Information concerning the effect of Bt and its possible application to the
      biocontrol of synathropic mites is rare. The toxic effect of Bacillus
      thuringiensis var. tenebrionis producing Cry3A toxin was tested on the mites
      Acarus siro L., Tyrophagus putrescentiae (Schrank), Dermatophagoides farinae
      Hughes, and Lepidoglyphus destructor (Schrank) via feeding tests. Fifty mites
      were reared on Bt additive diets in concentrations that ranged from 0 to 100 mg
      g(-1) under optimal conditions for their development. After 21 days, the mites
      were counted and the final populations were analyzed using a polynomial
      regression model. The Bt diet suppressed population growth of the four mite
      species. The fitted doses of Bt for 50% suppression of population growth were
      diets ranging from 25 to 38 mg g(-1). There were no remarkable differences among
      species. Possible applications of Bt for the control of synanthropic mites are
      discussed.

PMID- 19381845
TI  - Metastatic gene signatures and emerging novel prognostic tests in the management
      of early stage breast cancer.
AB  - Gene expression profiling using DNA microarrays allows simultaneous measurement
      of thousands of mRNA transcripts in a single experiment. Results from gene
      expression profiling studies have fundamentally altered our view of breast
      cancer, which is no longer regarded as a single disease but as several
      molecularly and biologically distinct neoplastic diseases. This technology has
      also yielded novel diagnostic assays that have started to have an impact on
      clinical care. This is a rapidly evolving field, and the constraints of space do
      not allow us to discuss many of the published studies. Therefore, in this review,
      we will summarize the results of those gene expression studies that are
      conceptually and practically most important and discuss some of the limitations
      and the future promise of this technology.

PMID- 19381846
TI  - Raf-1: a novel cardiac troponin T kinase.
AB  - Phosphorylation of cardiac troponin is a key mechanism involved in regulation of
      contractile function. In vitro kinase assays revealed that lysates prepared from
      resting cardiomyocytes contain cardiac troponin I (cTnI) and cTnT kinase
      activity. cTnI phosphorylation is inhibited by pharmacologic inhibitors of PKA,
      PKC, Rho kinase and PKC effectors such as RSK and PKD; these kinase inhibitors do
      not inhibit phosphorylation of cTnT. Rather, cTnT phosphorylation is decreased by
      the Raf inhibitor GW5074. In vitro kinase assays show that recombinant Raf
      phosphorylates cTnT, and that Raf-dependent cTnT phosphorylation is abrogated by
      a T206E substitution; Raf does not phosphorylate cTnI. These studies identify Raf
      dependent cTnT-Thr(206) phosphorylation as a novel mechanism that would link
      growth factor-dependent signaling pathways to dynamic changes in cardiac
      contractile function.

PMID- 19381847
TI  - Application of multivariate statistical approach to identify heavy metal sources
      in bottom soil of the Seyhan River (Adana), Turkey.
AB  - In this study, freshly deposited soils were sampled from the Seyhan River
      (Turkey) from the exit of the Seyhan Dam to the Adana exit. Heavy metal contents
      were measured with X-ray fluorescence spectrometer. Multivariate statistical
      approach is used to identify the sources of heavy metals and other elements in
      soil samples. Considering the size of anomalies, metals are ranked as
      Co>Pb>Cr>Zn>Al. Based on the hierarchical cluster analysis results, three
      clusters were observed. P, Mg, Ti, Fe, Ca, Na, K, Al, Si, and Nb form the first
      cluster, Zn, Sr, Pb, and Cr associated as the second cluster, and Ba and Co form
      the third cluster. Three factors computed from principal component analysis are
      explained with a cumulative variance of 95%. The first factor is defined with
      "high background lithogenic factor" Co, the second factor with "local industrial
      factor" Pb, Cr, Ba, and Mg, and the third factor with "natural factor" Cr and Pb.

PMID- 19381849
TI  - Molecular Diversity: seminal reviews, perspectives, and research articles.

PMID- 19381848
TI  - Organization and promoter analysis of the zebrafish (Danio rerio) chemokine gene
      (CXC-64) promoter.
AB  - Zebrafish CXC-64, a chemokine representing a superfamily of chemotactic cytokines
      present in fish, is involved in recruitment, activation, and response to
      inflammatory stimulation. We cloned and sequenced the genomic DNA of the
      zebrafish CXC-64 chemokine; it was most similar to CXCL11 from humans and CXCL10
      from a catfish. The zebrafish CXC-64 gene is approximately 4.0 kb long and has a
      four-exon, three-intron structure common to the human CXCL11 gene. However, the
      promoter region includes a typical TATA box and multi-transcription factor
      binding sequences. To understand the roles of lipopolysaccharide (LPS), poly
      I:poly C, and tumor necrosis factor (TNF)-alpha in regulating zebrafish CXC-64
      expression, serial deletions were made in the promoter region of this clone.
      Different fragments of the zebrafish CXC-64 5'-flanking region were transfected
      into RAW264.7 (mouse macrophage; Abelson murine leukemia virus transformed) and
      zfl (zebrafish liver) cells and then treated with 0, 10, 50, 100, and 200 ng/ml
      LPS, poly I:poly C, or TNF-alpha. The results showed that the promoter activity
      presented dose-dependent effects in LPS-treated RAW264.7 cells, TNF-alpha-treated
      RAW264.7 cells, and LPS-treated zfl cells. These results reveal that the
      zebrafish CXC-64 chemokine gene promoter region can be induced by LPS in both
      human and fish cell lines, which suggests that it plays an important role in
      regulating LPS.

PMID- 19381850
TI  - Efficient and green synthesis of tetrasubstituted pyrroles promoted by task
      specific basic ionic liquids as catalyst in aqueous media.
AB  - Synthesis of tetrasubstituted pyrroles by the three-component condensation
      reaction of acid chlorides, dialkyl acetylenedicarboxylates, and amino acids in
      the presence of various room-temperature ionic liquids (RTILs) as catalysts in
      water is reported. Among the ionic liquids used, the basic functionalized ionic
      liquid, butyl methyl imidazolium hydroxide [bmim]OH, was the most effective
      catalyst. The influence of reaction temperature, reaction time, and amount of
      ionic liquid on the reaction was investigated. The [bmim]OH/H(2)O catalyst system
      could be reused for at least five recycles without appreciable loss of
      efficiency.

PMID- 19381852
TI  - One hundred years of Meldrum's acid: advances in the synthesis of pyridine and
      pyrimidine derivatives.
AB  - A general review (138 references) focused on the recent advances in the
      application of Meldrum's acid reactivity for synthesis of diverse pyridine and
      pyrimidine derivatives, mostly small and drug-like molecules is presented.

PMID- 19381853
TI  - Enhanced single copy integration events in corn via particle bombardment using
      low quantities of DNA.
AB  - Transgene copy number is an important criterion for determining the utility of
      transgenic events. Single copy integration events are highly desirable when the
      objective is to produce marker free plants through segregation or when it is
      necessary to introgress different transgenes into commercial cultivars from
      different transgenic events. In contrast multi-copy events are advocated by
      several authors for higher expression of the transgene. Till recently, it was
      thought that employment of the particle gun for transformation results in the
      production of a high proportion of multi-copy events often with complex
      integration pattern when compared to Agrobacterium-mediated transformation.
      However, it has been demonstrated that usage of cassette DNA for bombardment in
      place of whole plasmids would result in simple insertion pattern of the
      transgenes. While investigating the effect of varying the cassette DNA amount on
      stable transformation, the frequency of occurrence of low copy events was
      observed to increase when lower doses of cassette DNA was employed for
      bombardment. Large scale experimentation with rigorous statistical analysis
      performed to verify the above observations employing Helium gun and the Electric
      discharge gun for gene delivery confirmed the above observations. Helium gun
      experiments involving production of more than 1,600 corn events consistently
      yielded single copy events at higher frequencies at lower cassette DNA load (46%
      at 2.5 ng/shot) as compared to higher cassette DNA load (29% at 25 ng/shot)
      across 18 independent experiments. Results were nearly identical with the
      Electric discharge particle gun device where single copy events were recovered at
      frequencies of 54% at 2.5 ng cassettes DNA per shot as compared to 18% at 25 ng
      cassette DNA per shot. The transformation frequency declined from 41 to 34%
      (Helium gun) and from 48 to 31% (Electric discharge gun) with reduction in
      cassette DNA quantity from 25 to 2.5 ng per shot. This reduction in the
      transformation frequency is more than compensated by the savings in time and
      effort involved in the production and screening of events if the desired outcome
      is single copy events. These results demonstrate the flexibility of the particle
      gun method for controlling the frequency of production of either low copy or high
      copy events by altering the quantity of cassette DNA used for bombardment. The
      transgene expression levels over generations in relation to its integration need
      further investigations.

PMID- 19381854
TI  - Metachronous bilateral renal cell carcinoma with an interval of more than 10
      years.
AB  - OBJECTIVE: Renal cell carcinoma (RCC) is notorious for late recurrence. However,
      little is known about late recurrence in the contralateral kidney, that is,
      metachronous bilateral RCC after a long interval. Unlike other recurrent sites,
      cancer in the contralateral kidney may be a metastatic or a new and independent
      lesion. The clinical characteristics of such cases formed the basis of this
      study. MATERIALS AND METHODS: Thirteen well-described cases in the English and
      Japanese literature were reviewed. Each clinical parameter, such as age, sex,
      size and number of the tumor(s), and interval, was divided into two groups and
      compared using the log rank test. RESULTS: The clinical characteristics of these
      cases were similar to those of sporadic RCC cases, and no specific clinical or
      pathological features in these cases were found. As to the prognosis, among
      clinical parameters, cases with multiple second tumors had a favorable outcome
      compared with cases with a single second tumor. CONCLUSIONS: Multiple second
      tumors may be suggestive of metastasis from the first tumor. The favorable
      outcome in this group reflects the gentle biological nature of these slow-growing
      tumors that had taken a long time to become clinically obvious. Because of the
      limited number of cases in this study, further investigation will be needed.

PMID- 19381855
TI  - Oral tamoxifen citrate treatment is more effective in normogonadotropic patients
      who have follicle-stimulating hormone levels within the lower half of normal.
AB  - OBJECTIVE: To identify a subgroup of normogonadotropic men who may benefit
      relatively more from TC (tamoxifen citrate; a widely prescribed drug for male
      infertility) among those with FSH (follicle-stimulating hormone) values in the
      lower or higher halves of the normal range. PATIENTS AND METHODS: In this
      retrospective study, 120 normogonadotropic infertile men with idiopathic
      oligozoospermia were included. All patients received 20 mg TC daily as a single
      dose for 6 months, and semen analysis and hormone levels were analyzed after 6
      months, with the values being compared with those before treatment. RESULTS: The
      FSH, luteinizing hormone and testosterone levels were significantly increased
      after the use of oral TC 20 mg daily. The sperm counts of the patients in the
      lower initial FSH group had a significantly higher increase in sperm count and
      concentration compared to the relatively higher FSH group. CONCLUSION: This study
      revealed that initial FSH values can be used as a marker to estimate the
      probability that a patient will benefit from oral TC therapy. Patients in the
      lower FSH group had statistically higher chances of having higher sperm counts
      after treatment, and it is rational to advise these patients to receive 6 months
      of oral TC therapy. However, before drawing firm conclusions from this
      retrospective study, these results should be confirmed with double-blind, placebo
      controlled, randomized trials.

PMID- 19381856
TI  - Incidentally detected ureteral fibroepithelial polyps in children: is endoscopic
      treatment of them really necessary?
AB  - OBJECTIVE: Fibroepithelial polyps (FEPs) are the most common benign lesions of
      the ureter. However, FEPs of the ureter accompanied by calculi are rare. In this
      study, we reviewed our experiences with five children having FEP associated with
      ureteral calculi to define more clearly this entity and its outcome following
      observation. MATERIALS AND METHODS: We identified five children who were
      intraoperatively found to have FEP associated with ureteral calculi during the
      period 2000-2008. RESULTS: The patients included four males and one female, and
      the average age of these patients was 6.4 years (range 4-9). The main symptoms
      were flank pain (five patients), hematuria (four patients), and dysuria (two
      patients). Radiographically, all patients showed complete ureteral obstruction
      due to distal ureter stone and hydronephrosis. Fibroepithelial polyps and stones
      were located left distal ureter in all children. These polyps were 1-2 cm, with a
      mean size of 1.5 cm. Stone sizes ranged from 5 to 13 mm (mean 8.8 mm). The stones
      were smashed into smaller fragments using a pneumatic lithotriptor, and the
      pieces were removed with forceps. After the lithotripsy, the polyps were grasped
      with biopsy forceps and punch biopsies were done. FEPs were diagnosed in all
      cases by postoperative histological examination. During the follow-up period of
      these patients, none of the FEPs displayed any growth or symptom. CONCLUSIONS:
      Due to the potential complications during the ureteroscopic resection, our
      opinion is to observe the small FEPs without joint symptoms and hydronephrosis.

PMID- 19381851
TI  - Controlled microwave heating in modern organic synthesis: highlights from the
      2004-2008 literature.
AB  - Direct and rapid heating by microwave irradiation in combination with sealed
      vessel processing in many cases enables reactions to be carried out in a fraction
      of the time generally required using conventional conditions. This makes
      microwave chemistry an ideal tool for rapid reaction scouting and optimization of
      conditions, allowing very rapid progress through hypotheses-experiment-results
      iterations. The speed at which multiple variations of reaction conditions can be
      performed allows a morning discussion of "What should we try?" to become an after
      lunch discussion of "What were the results?" Not surprisingly, therefore, many
      scientists both in academia and industry have turned to microwave synthesis as a
      front-line methodology for their projects. In this review, more than 220
      published examples of microwave-assisted synthetic organic transformations from
      the 2004 to 2008 literature are discussed. An additional ca. 500 reaction schemes
      are presented in the Electronic Supplementary Material, providing the reader with
      an overall number of ca. 930 references in this fast-moving and exciting field.

PMID- 19381858
TI  - A metabolic and functional overview of brain aging linked to neurological
      disorders.
AB  - Close correlations have recently been shown among the late onset complications
      encountered in diabetes and aging linked to neurobiological disorders. Aging in
      females and males is considered as the end of natural protection against age
      related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's
      disease and Parkinson's disease, dementia, cognitive dysfunction and
      hypernatremia. Beside the sex hormones other hormonal changes are also known to
      occur during aging and many common problems encountered in the aging process can
      be related to neuroendocrine phenomena. Diabetes mellitus is associated with
      moderate cognitive deficits and neurophysiologic and structural changes in the
      brain, a condition that may be referred to as diabetes encephalopathy; diabetes
      increases the risk of dementia especially in the elderly. The current view is
      that the diabetic brain features many symptoms that are best described as
      accelerated brain aging. This review presents and compares biochemical,
      physiological, electrophysiological, molecular, and pathological data from
      neuronal tissue of aging and hormone treated control and diabetic animals to
      arrive at the similarities among the two naturally occuring physiological
      conditions. Animal models can make a substantial contribution to understanding of
      the pathogenesis, which share many features with mechanism underlying brain
      aging. By studying the pathogenesis, targets for pharmacology can be identified,
      finally leading to delay or prevention of these complications. Antiaging
      strategies using hormone therapy, chemical and herbal compounds were carried out
      for reversal of aging effects. Neuronal markers have been presented in this
      review and similarities in changes were seen among the aging, diabetes and
      hormone treated (estrogen, DHEA and insulin) brains from these animals. A close
      correlation was observed in parameters like oxidative stress, enzyme changes, and
      pathological changes like lipofuscin accumulation in aging and diabetic brain.

PMID- 19381857
TI  - Is male fertility associated with type 2 diabetes mellitus?
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of infertility
      in Qatari men with Diabetes Mellitus (T2DM) and to examine the association
      between T2DM and infertility. DESIGN: This is a cross-sectional study. SETTING:
      The survey was conducted at Primary Health Care Centers during a period from
      January 2008 to June 2008. SUBJECTS: The selected subjects for the study were
      Qatari men aged 25-60 years who were married for more than 1 year. A total of
      1,165 men were approached and only 857 men gave consent, giving a response rate
      of 73.6%. METHODS: Face-to-face interviews were based on a questionnaire that
      included variables on socio-demographic characteristics, type of infertility in
      men, life style habits, type of environmental exposures, and common diseases
      found among infertile men. All studied men were recruited using cluster random
      sampling at 13 randomly selected primary health care centers at the Hamad Medical
      Corporation. RESULTS: The prevalence of infertility in Qatari T2DM men was 35.1%.
      The prevalence of primary infertility (16%) and secondary infertility (19.1%) was
      significantly higher in diabetic men (P = 0.003) as compared to non-diabetic men.
      Also, secondary infertility was higher than primary infertility in our studied
      Qatari diabetic men. Half of the diabetic infertile men were overweight (50.6%)
      and 29.1% of them were obese. The smoking habit was more common in diabetic
      infertile men (45.6%) than in diabetic fertile men (33.6%). Multivariate logistic
      regression analysis confirmed that age (P < 0.001), smoking habits (ex-smokers, P
      = 0.003 and current smokers, P = 0.001) and obesity (P < 0.001) were the
      significant major contributors for infertility in diabetic men. Obesity was the
      leading contributor for the infertility. Other co-morbid factors associated with
      infertility in diabetic men were hypertension, erectile dysfunction, and
      varicocele. CONCLUSION: The present study findings revealed that there is a
      strong association between male infertility and Diabetes Mellitus. In Qatari
      diabetic men, male infertility is high and a significant public health problem in
      Qatar. The study results confirmed a strong association between T2DM and
      infertility in Qatari men.

PMID- 19381859
TI  - Safety of an injection with a mixture of extracts from Herba Artemisiae annuae,
      Fructus Gardeniae and Flos Lonicerae.
AB  - OBJECTIVE: This study aimed to evaluate the safety for an injection with a
      mixture of extracts from Herba Artemisiae annuae, Fructus Gardeniae and Flos
      Lonicerae and to determine the risk factors that may affect its adverse drug
      reactions. METHODS: A drug-oriented prospective observational study was
      performed. Physicians filled in clinical observation forms with detailed
      information of the patients including general information, drug information,
      therapeutic effects and adverse drug events. The adverse drug reaction factors
      were analyzed by both mono-factor and multiple-factor logistic regression
      methods. RESULTS: From April to July 2007, we collected 12,427 observation forms
      from 46 hospitals in Jiangsu Province of China. Among the 11,707 observation
      forms we analyzed, 8,074 patients were children younger than 14 years old (69%).
      Among 51 reported adverse drug events, 45 cases were adverse drug reactions. The
      total adverse drug reaction incidence of the injection was 0.38%. While most
      adverse drug reactions were previously known (e.g., rash, pruritus, vomiting and
      diarrhea), we observed three new ADR symptoms: shiver, phlebitis and anhelation.
      All the adverse drug reactions were controlled very well through the follow-up
      therapy, and none of them was life threatening. The mono-factor analysis showed
      that adverse drug reactions of the injection were significantly correlated with
      total medication dose (P = 0.0049) and combination medication (P = 0.0143),
      especially with antimicrobial drugs (P = 0.0079) and macrolides (P = 0.0017). The
      multiple factor analysis confirmed these results: medication dosage and
      combination medication had a crucial impact on adverse drug reactions of the
      injection; the risk was increased by 24.8% (the estimated value of relative risk
      was 1.248, 95% confidence interval: 1.054-1.479) and 89% (1.890, 1.001-3.566),
      respectively. CONCLUSION: The total adverse drug reaction incidence of the
      injection was 0.38% and lower than we expected. Moreover, we observed three new
      adverse drug reactions, none of which was severe.

PMID- 19381860
TI  - The A14-scale: development and evaluation of a questionnaire for assessment of
      adherence and individual barriers.
AB  - OBJECTIVE: To develop a questionnaire ("A14") for the description of adherence
      and individual barriers as basis for adherence-enhancing interventions in the
      clinical and pharmaceutical setting, and to compare it to the validated German
      MMAS (Morisky Medication Adherence Scale). METHOD: Fourteen questions with a 5
      item likert-scale from "never" (4) to "very often" (0) were given to 150 medical
      inpatients. According to their score, patients were classified into non-adherent
      (score <50) or adherent (score 50-56). On the dichotomous MMAS, "yes" is scored 0
      and "no" 1 point, a total score of 4 indicating adherence. Patients with complete
      scales were compared with the remaining patients regarding socio-demographic
      factors. Descriptive statistics, Cronbach's Alpha, Spearman correlation, and
      kappa were computed. RESULTS: Eighty-three participants completed both scales.
      Patients with missing values differed significantly regarding age, education, and
      adherence according to MMAS. Cronbach's Alpha for A14 was 0.861. MMAS and A14
      median total scores were 4 and 52, respectively. About 39.5% of patients were non
      adherent as per MMAS compared to 40% as per A14; kappa was 0.262 (P = 0.016). The
      total scores correlated with a Rho-value of 0.43 (P < 0.001). CONCLUSION: The A14
      scale showed good internal consistency and a significant correlation with the
      MMAS suggesting that it merits further investigation.

PMID- 19381861
TI  - Pulsed EPR spectroscopy.

PMID- 19381862
TI  - A simple colorimetric determination of the manganese content in photosynthetic
      membranes.
AB  - The functional Mn content of intact photosystem II membrane fragments was
      measured as 4.06 +/- 0.13 Mn/reaction center when determined using a simple,
      sensitive colorimetric assay that will also work with thylakoids and core
      complexes. This procedure requires minimal sample material, does not need
      expensive assay equipment, requires four simple steps, and only takes 20-30 min
      to perform. These include (a) removal of the adventitious Mn ions by CaCl(2)
      treatment of the membranes, (b) extraction of the Mn from the O(2)-evolving
      complex with hydrochloric acid, (c) purification of the extract by centrifugation
      followed by filtration of the supernatant through an Acrodisc syringe filter (0.2
      mum nylon membrane), and (d) colorimetric determination of Mn in the extract
      using the reaction of the chromogenic agent, 3,3',5,5'-tetramethylbenzidine, with
      previously oxidized Mn(II) cations carried out at high pH. The colorimetric assay
      itself has been used previously by Serrat (Mikrochim Acta 129:77-80, 1998) for
      assaying Mn concentrations in sea water and drinking water.

PMID- 19381864
TI  - Sensory integration intervention: historical concepts, treatment strategies and
      clinical experiences in three patients with succinic semialdehyde dehydrogenase
      (SSADH) deficiency.
AB  - This paper is a review of clinical experiences providing developmental therapy
      services for three boys diagnosed with paediatric neurotransmitter disease. The
      clinical presentation of paediatric neurotransmitter diseases might parallel
      other diagnostic characteristics seen in a typical paediatric therapy clinic
      (i.e. hypotonia, motor and cognitive delays, coordination, expressive speech, and
      ocular motor difficulties.) From the clinical perspective of the author, sensory
      integrative function is but one aspect of a thorough evaluation and treatment
      plan for all patients. The manifestations of sensory integration dysfunction
      (SID), also known as sensory processing dysfunction (SPD), can occur alone or be
      concurrent with a variety of known medical, behavioural and neurological
      diagnoses. These manifestations of SPD can include, but are not limited to:
      hypotonia, hyperactivity, irritability, distractibility, attention difficulties,
      learning difficulties, clumsiness and incoordination, instability, poor motor
      skills, social-emotional difficulties, and behavioural problems. This paper
      summarizes the theory and practice applications of sensory integration. The
      author discusses clinical experiences providing occupational therapy services
      utilizing sensory integration methods and strategies with clients who were
      eventually diagnosed with SSADH deficiency.

PMID- 19381865
TI  - Early-onset hyperargininaemia: a severe disorder?
AB  - Hyperargininaemia is a rare inborn error of metabolism due to a defect in the
      final step of the urea cycle. Infantile onset is the most common presentation
      with recurrent vomiting and psychomotor delay associated with spastic
      paraparesis; chronic hyperammonaemia is often overlooked. Neonatal and early
      onset presentations are very uncommon and their clinical course not well
      described. We report on a 3-week-old hyperargininaemic girl who presented with
      neurological deterioration associated with liver failure and 47-day ammonia
      intoxication before diagnosis could be made and treatment started. Despite
      appropriate but delayed treatment, our patient exhibited severe psychomotor delay
      at age 1 year. CONCLUSION: Early identification and management of this rare but
      potentially treatable affection is crucial as delayed management may result in
      poor neurological outcome.

PMID- 19381866
TI  - Hemodynamic variables during stress testing can predict referral to early
      catheterization but failed to show a prognostic impact on emerging cardiac events
      in patients aged 70 years and older undergoing exercise (99m)Tc-sestamibi
      myocardial perfusion scintigraphy.
AB  - The aim of the present study was to evaluate the prognostic value of hemodynamic
      variables during ergometric stress testing for (99m)Tc-sestamibi myocardial
      perfusion scintigraphy (MPS) as compared to several patient-related variables and
      MPS results with regard to referral to early coronary angiography (<3 months
      after MPS; CA) as well as cardiac event (CE) free survival in a study population
      aged > or =70 years. About 90 patients aged > or =70 years (74.5 +/- 3.6 years)
      who underwent ergometric stress/rest MPS were included in this study. About 19
      hemodynamic variables during stress testing were assessed. Semiquantitative
      visual interpretation of MPS images were performed and Summed-Stress-(SSS),
      Summed-Difference-, and Summed-Rest-Scores were calculated. Emerging CE comprised
      myocardial revascularization and -infarction as well as cardiac-related death.
      Multivariate logistic regression analyses were performed for evaluation of
      independent prognostic impact of hemodynamic-, MPS- and clinical-variables with
      regard to referral to early catheterization as well as emerging CE. Kaplan-Meier
      survival- and log rank analyses were calculated for assessment of CE free
      survival. History of CAD (Odds ratio; OR: 99.3), low rest heart rate (OR: 14.9)
      and low peak systolic blood pressure (OR: 15.4) during ergometric stress testing
      as well as pathological SSS (OR: 48.4) were significantly associated with
      referral to CA. History of ischemic ECG (OR: 4.7) and pathological SSS (OR: 3.7)
      independently predicted emerging CE and were associated with a lower CE free
      survival. In patients aged > or =70 years, CA is independently predicted by
      clinical variables, pathological results of MPS and hemodynamic variables. In
      contrast, hemodynamic response to stress testing failed to show any predictive
      impact on emerging CE.

PMID- 19381867
TI  - Determinants of vessel contrast in BMI-adapted low dose CT coronary angiography
      with prospective ECG-triggering.
AB  - We evaluated the determinants of vessel contrast in prospectively ECG-triggered
      CT coronary angiography (CTCA). Seventy patients underwent low-dose CTCA using
      body mass index (BMI)-adapted tube parameters and a fixed contrast material
      bolus. Contrast to noise ratio (CNR) was calculated from contrast (between
      coronaries and perivascular tissue) and image noise (standard deviation of aortic
      attenuation). Cardiac output (CO) was calculated from gated (99m)Tc-tetrofosmin
      SPECT. Mean radiation dose was 2.13 +/- 0.69 mSv. Image noise was not affected by
      BMI (r = 0.1, P = 0.36), while CNR was inversely related to body surface area
      (BSA) (r = -0.5, P < 0.001) and CO (r = -0.45, P < 0.001). After successfully
      overcoming the impact of BMI on image noise by adapting tube parameters, CNR
      mainly depends on coronary vessel contrast. The latter reflects the dilution of
      the contrast material by blood volume and CO, which are both correlated to BSA.
      Therefore, BSA adapted contrast administration may help to compensate for this
      effect.

PMID- 19381868
TI  - Inhibitory effects of cysteine and cysteine derivatives on germination of
      sporangiospores and hyphal growth of different Zygomycetes.
AB  - The in vitro antifungal activity of cysteine (D- and L-cysteine) and its four
      derivatives (L-cysteine-methyl-ester, N-acetyl-cysteine, N-isobutyryl-D-cysteine,
      and N-isobutyryl-L-cysteine) were investigated on 20 fungal isolates representing
      16 genera (Absidia, Actinomucor, Backusella, Gilbertella, Micromucor,
      Mortierella, Mucor, Mycotypha, Phycomyces, Rhizomucor, Rhizopus, Saksenaea,
      Syncephalastrum, Thamnostylum, Umbellopsis, and Zygorynchus). The inhibitory
      potential of different concentrations of these compounds, ranging from 0.625 to
      10 mM, were investigated on the germination of sporangiospores as well as on
      hyphal extension, using broth microdilution method and agar plate test. Treatment
      with cysteine and its derivatives resulted in a strong inhibition in most studied
      strains. At 10 mM of compounds, complete blockage of growth was observed for some
      isolates. Sensitive species exhibited severe changes in colony morphology in the
      presence of 10 mM L-cysteine, N-acetyl-cysteine, and N-isobutyryl-L-cysteine.
      Microscopic observations revealed that 10 mM N-acetyl-cysteine induced dramatic
      modifications in the structural organization of the hyphae. Results suggest that
      cysteine and its derivatives have a therapeutic potential against fungal
      infections caused by Zygomycetes species.

PMID- 19381870
TI  - Identification of a cathepsin D potentially involved in H2A cleavage from scallop
      Chlamys farreri.
AB  - We report here a cDNA and its deduced amino acid sequence encoding a cathepsin D
      like, aspartic protease from Chlamys farreri (denoted as CfCD) by expressed
      sequence tag and rapid amplification of cDNA ends techniques. The cDNA of CfCD
      consisted of 1,810 nucleotides with a canonical polyadenylation signal sequence
      AATAAA and a polyA tail, encoding a short signal peptide of 18 amino acids, a pro
      enzyme peptide of 29 amino acid residues, and a mature enzyme of 349 residues.
      The deduced amino acid sequence of CfCD was significant homology to CDs from
      human, fish and invertebrates. Two conserved catalytic motifs (VFDTGSSNLWV and
      AIADTGTSLLVG) and two potential N-glycosylation sites were also identified in the
      deduced amino acid sequence of CfCD. All this characteristics indicated CfCD
      should be a member of CDs family. The mRNA spatial expression of CfCD in mantle,
      gonad, gill, hemocytes, hepatopancreas and adductor muscle was examined by
      quantitative real-time PCR. mRNA transcripts of CfCD could be detected in all
      tissues with the highest expression level in hepatopancreas. After 8 h Vibrio
      anguillarum challenge, the expression level of CfCD changed significantly in all
      examined tissues except mantle (P = 0.183) and hemocytes (P = 0.069). The
      information generated in the present study would be helpful for future studies
      aiming at investigating the detailed functions of cathepsin D from marine
      invertebrates.

PMID- 19381871
TI  - "It's intense, you know." Nurses' experiences in caring for patients requesting
      euthanasia.
AB  - The Belgian Act on Euthanasia came into force on 23 September 2002, making
      Belgium the second country--after the Netherlands--to decriminalize euthanasia
      under certain due-care conditions. Since then, Belgian nurses have been
      increasingly involved in euthanasia care. In this paper, we report a qualitative
      study based on in-depth interviews with 18 nurses from Flanders (the Dutch
      speaking part of Belgium) who have had experience in caring for patients
      requesting euthanasia since May 2002 (the approval of the Act). We found that the
      care process for patients requesting euthanasia is a complex and dynamic process,
      consisting of several stages, starting from the period preceding the euthanasia
      request and ending with the aftercare stage. When asked after the way in which
      they experience their involvement in the euthanasia care process, all nurses
      described it as a grave and difficult process, not only on an organizational and
      practical level, but also on an emotional level. "Intense" is the dominant
      feeling experienced by nurses. This is compounded by the presence of other
      feelings such as great concern and responsibility on the one hand, being content
      in truly helping the patient to die serenely, and doing everything in one's power
      to contribute to this; but also feeling unreal and ambivalent on the other hand,
      because death is arranged. Nurses feel a discrepancy, because although it is a
      nice death, which happens in dignity and with respect, it is also an unnatural
      death. The clinical ethical implications of these findings are discussed.

PMID- 19381872
TI  - Self-rated health in persons with spinal cord injury: relationship of secondary
      conditions, function and health status.
AB  - OBJECTIVE: Self-rated health is used frequently as a measure of health in the
      general population, and increasingly with persons with disabilities. However, its
      meaning and its relationship with other measures of self-reported health (health
      status and secondary conditions) are not well understood for this group. The
      purpose of the present study was to use a conceptual model to examine the
      structure of self-rated health with persons with spinal cord injuries. METHODS: A
      US sample of 270 adults with mobility impairment stemming from spinal cord injury
      (SCI) provided data on three measures of self-reported health that differ in
      degree of subjectivity: physical problems common to SCI, four domains of health
      status from the SF-36, and a single item on self-rated health. Data were compared
      with the norm sample of the SF-36. The conceptual model was tested using path
      analyses. RESULTS: SF-36 scores were lower on three of four domains compared with
      the norm sample. The conceptual model analyses indicated that 35% of variance in
      self-rated health is accounted for through direct relationship with physical
      secondary conditions common to persons with SCI and as mediated through SF-36
      domains of Role Physical and Vitality. The SF-36 domain of Physical Function was
      statistically unrelated to self-rated health. CONCLUSION: The conceptual model of
      self-rated health was verified in a sample of persons with SCI. Importantly, the
      SF-36 domain of Physical Function does not relate to self-rated health for this
      group. Its inclusion in measures of self-reported for disability populations
      creates difficulty without apparent benefit.

PMID- 19381873
TI  - A simple method for cryopreservation of MDBK cells using trehalose and storage at
      -80 degrees C.
AB  - Madin Darby bovine kidney cells were stored at -80 degrees C using trehalose.
      Trehalose was loaded into the cells by fluid-phase endocytosis that was
      facilitated by heat shock at 40 degrees C for 1 h. Loaded cells were gradually
      frozen and stored at -80 degrees C. Revival of cells was done by quick thawing
      and immediately seeded in the tissue culture flasks. The membrane integrity of
      cells was measured at different times post-storage by trypan blue dye exclusion
      method. It was estimated to be 96.23, 73.84, 57.33, 54.36, 25.47, 50.53 and
      46.86% at 0, 7, 60, 90, 120, 160 and 180-day post-storage, respectively.
      Cryostorage of cells at -80 degrees C may help to reduce the use of liquid
      nitrogen.

PMID- 19381874
TI  - What's in an intron? CCN1 mRNA splicing in cancer.
AB  - The CCN family of matricellular signaling regulators shares a common domain
      structure. Variants of individual CCN proteins exist, which contain different
      combinations of these domains. Although mRNA splicing is likely to play a key
      role on CCN biology, this hypothesis has not been thoroughly tested. In a recent
      report, Hirschfeld and colleagues (Cancer Res 69:2082-90, 2009), show that CCN1
      (cyr61) mRNA is normally present in a form in which intron 3 is retained. In
      cancers, or upon hypoxia, intron 3 is removed resulting in the appearance of CCN1
      protein. The significance of this paper is discussed.

PMID- 19381875
TI  - Primary intraosseous adenoid cystic carcinoma of the mandible: histopathological
      and immunohistochemical analysis.
AB  - Primary intraosseous salivary gland tumors of the mandible are rare, with
      mucopidermoid carcinoma being the most frequent, followed by adenoid cystic
      carcinoma (ACC). We present a case of a central ACC involving the mandible of a
      46-year-old man. He presented an indurated swelling on the vestibular aspect of
      the left mandibular body and ipsilateral paraesthesia of the lower lip. A
      panoramic radiography revealed a large radiolucent area, with irregular margins,
      involving the body and ramus of the left mandible, and CT scan confirmed that the
      lesion was confined within the mandibular bone. The histopathological features
      were of an ACC. CT scan also revealed multiple nodular lesions in both lungs
      suggestive of metastases. The patient was surgically treated by hemi
      mandibulectomy. The patient is well with no evidences of recurrences in the
      mandible. The present case shows that the clinical and immunohistochemical
      profile of primary intraosseous ACC is similar to what is found in ACC involving
      the salivary glands.

PMID- 19381876
TI  - Clinicopathologic and molecular features of epidermal growth factor receptor
      T790M mutation and c-MET amplification in tyrosine kinase inhibitor-resistant
      Chinese non-small cell lung cancer.
AB  - To investigate the clinicopathologic and molecular features of the T790M mutation
      and c-MET amplification in a cohort of Chinese non-small cell lung cancer (NSCLC)
      patients resistant to epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors (TKIs). EGFR TKI-resistant NSCLC patients (n = 29) and corresponding
      tumor specimens, and 53 samples of postoperative TKI-naive NSCLC patients were
      collected. EGFR exon 19, 20, and 21 mutations were analyzed. And c-MET gene copy
      number was determined. The EGFR T790M mutation in exon 20 was not detected in the
      population of 53 TKI-naive patients, but found in 48.3% (14/29) of the enrolled
      TKI-resistant patients. c-MET was amplified in 3.8% (2/53) of the TKI-naive NSCLC
      patients and highly amplified in 17.2% (5/29) of the cohort. Most of T790M
      mutations were frequently associated with non-smoker, adenocarcinoma and EGFR
      activating mutations. Three male patients with T790M mutation occurred with wild
      type EGFR, and were resistant to the treatments following TKI resistance.
      Features of c-MET amplification in TKI-naive patients were indistinguishable from
      TKI-resistant patients. In the group of wild-type EGFR, patients with T790M
      mutation had median progression free survival (PFS) and overall survival (OS) as
      9.6 months and 12.6 months, respectively; whereas the median PFS and OS of c-MET
      amplified patients was 4.1 months and 8.0 months, respectively. These results
      suggest that EGFR T790M mutation and c-MET amplification can occur in TKI
      resistant NSCLC with wild-type EGFR, and these genetic defects might be related
      to different survival outcome. c-MET amplification in TKI-naive or -resistant
      patients might share similarities in clinicopathologic features.

PMID- 19381877
TI  - GABA receptor expression in benign and malignant thyroid tumors.
AB  - Neurotransmitter systems have recently been shown to be involved in multiple
      malignancies including breast, colon and prostate cancers. The role of
      neurotransmitters and neurotrophic factors has not yet been examined in thyroid
      cancer. To determine the possible involvement of neurotransmitter systems in
      thyroid carcinogenesis we characterized the patterns of gamma-aminobutyric acid
      (GABA) receptor expression in normal thyroid and thyroid tumors. We examined the
      expression patterns of the GABAergic system in 70 human thyroid tumor samples (13
      follicular adenomas, 14 follicular carcinomas, 43 papillary carcinomas) and
      adjacent normal thyroid by immunohistochemistry. GABAergic system mRNA expression
      in thyroid cancer cell lines derived from primary (FTC133) and metastatic tumors
      (FTC236 and FTC238) was examined by real time PCR. Overall, GABA receptor
      expression is increased in tumors compared to normal thyroid tissue. Expression
      of GABAA receptor beta2 was detected in the vasculature of normal thyroid and
      thyroid tumors but not in thyroid cancer cells. GABAA alpha2 was detected in
      metastatic-derived but not in primary-tumor derived cell lines. Expression levels
      of GABAB R2 and GABA receptor associated protein (GABARAP) are increased in
      adenomas and thyroid cancer suggesting their role in early stages of thyroid
      tumorigenesis. This study represents the first demonstration of GABA receptor
      expression in human thyroid tissue and suggests that the GABAergic system is
      involved in thyroid carcinogenesis.

PMID- 19381878
TI  - ST elevation myocardial infarction presenting after use of pseudoephedrine.

PMID- 19381879
TI  - Role of central calcitonin gene-related peptide (CGRP) in locomotor and anxiety-
      and depression-like behaviors in two mouse strains exhibiting a CGRP-dependent
      difference in thermal pain sensitivity.
AB  - We have previously shown that, in AKR and C57BL/6 mice, a genetic polymorphism
      results in differential expression of the peptide, calcitonin gene-related
      polypeptide (CGRP), explaining a strain difference in thermal pain sensitivity.
      Although CGRP is widely distributed in the brain, little is known about the
      effects of supraspinal CGRP. We used AKR and C57BL/6 mice as a model to explore
      the effects of centrally (intracerebroventricular) injected CGRP and the CGRP
      receptor antagonists, CGRP(8-37) and BIBN4096BS, in a series of behavioral
      assays. Locomotor activity was significantly increased in C57BL/6 mice following
      the injection of BIBN4096BS and in both strains after the administration of
      CGRP(8-37) into the third ventricle. CGRP increased paw-withdrawal latencies in
      C57BL/6 mice only, while decreasing depression-like behaviors in both strains in
      the forced-swimming test. CGRP and CGRP receptor antagonists failed to modulate
      activity in the elevated plus maze, a model of anxiety. Taken together, these
      results suggest a complex role for supraspinal CGRP systems in the regulation of
      locomotion, nociception, and depression-like behaviors.

PMID- 19381880
TI  - Protection of crayfish glial cells but not neurons from photodynamic injury by
      nerve growth factor.
AB  - Photodynamic treatment that causes intense oxidative stress and cell death is
      currently used in neurooncology. However, along with tumor cells, it may damage
      healthy neurons and glia. In order to study photodynamic effect on normal nerve
      and glial cells, we used crayfish stretch receptor, a simple system consisting of
      only two identified sensory neurons surrounded by glial cells. Photodynamic
      treatment induced firing abolition and necrosis of neurons as well as necrosis
      and apoptosis of glial cells. Nerve growth factor but not brain-derived
      neurotrophic factor or epidermal growth factor protected glial cells but not
      neurons from photoinduced necrosis and apoptosis. Inhibitors of tyrosine kinases
      or protein kinase JNK eliminated anti-apoptotic effect of nerve growth factor in
      photosensitized glial cells but not neurons. Therefore, these signaling proteins
      were involved in the anti-apoptotic activity of nerve growth factor. These data
      indicate the possible presence of receptors capable of recognizing murine nerve
      growth factor in crayfish glial cells. Thus, intercellular signaling mediated by
      nerve-growth-factor-like neurotrophin, receptor tyrosine kinase, and JNK may be
      involved in crayfish glia protection from apoptosis induced by photodynamic
      treatment.

PMID- 19381881
TI  - Reduced platelet activity is more common than reported anti-platelet medication
      use in patients with intracerebral hemorrhage.
AB  - BACKGROUND: Anti-platelet medication and reduced platelet activity are associated
      with an increased risk of death after intracerebral hemorrhage (ICH). The optimal
      assay for assessing platelet activity is not defined. We hypothesized that
      reduced platelet activity would be common after ICH. PATIENTS AND METHODS: We
      prospectively enrolled 72 consecutive patients with ICH and routinely measured
      platelet activity with both the PFA-100 (Siemens AG, Germany) and the VerifyNow
      ASA (Accumetrics, CA, USA) systems on admission. We prospectively recorded anti
      platelet medication use prior to ICH. RESULTS: VerifyNow-ASA measurements were
      associated with aspirin (P = 0.001) and clopidogrel (P = 0.01) use prior to ICH.
      Combined clopidogrel and aspirin therapy was more potent than either alone. Of 33
      patients with reduced platelet activity on the VerifyNow-ASA assay, 14 (42%) were
      not known to take anti-platelet agents. Of 27 patients with reduced platelet
      activity on the PFA-100, a related but different 14 (52%) were not known to take
      anti-platelet agents. There was a poor agreement between the assays (kappa =
      0.26, P = 0.07) on which patients had reduced platelet activity among the
      patients not known to take aspirin. CONCLUSIONS: A medication history does not
      reliably identify patients with reduced platelet activity after ICH, and this may
      explain studies that found no association between known aspirin use and outcomes.
      Future studies should screen for unknown use of anti-platelet medications after
      ICH. Neither assay perfectly identified patients who reportedly used anti
      platelet medication before ICH.

PMID- 19381882
TI  - TCD systolic spikes in a malignant MCA infarct.
AB  - INTRODUCTION: Malignant MCA infarction results in significant space occupying
      effect and intracranial pressure (ICP) increment. Due to the high mortality rate
      in such patients, the term malignant MCA infarction was coined. METHODS: We
      studied a patient who developed a sudden onset of slurred speech, right
      hemiplegia, and decreased level of arousal. Two days later CT scan showed a
      massive cerebral infarct, involving the left MCA territory. RESULTS: A
      transcranial Doppler exam showed a normal flow pattern in the right hemisphere,
      but in the left hemisphere systolic spikes without diastolic flow were observed
      in internal carotid artery, anterior cerebral artery, as well as in the MCA.
      CONCLUSIONS: The pathophysiologic mechanisms leading to BD might asymmetrically
      begin in cerebral hemispheres in malignant MCA infarcts.

PMID- 19381883
TI  - Novel GDAP1 mutation in a Turkish family with CMT2K (CMT2K with novel GDAP1
      mutation).
AB  - Mutations in the ganglioside-induced differentiation-associated protein 1 gene
      (GDAP1) cause Charcot-Marie-Tooth type 2 (CMT2), a severe autosomal recessive
      form of neuropathy associated with axonal phenotypes. It has been screened in
      this study for the presence of mutations in the coding region of GDAP1, which
      maps to chromosome 8q21, in a family with CMT2. To date, 29 mutations in the
      GDAP1 have been reported in patients of different ethnic origins. Here, we report
      a novel missense mutation (c.836A>G), and two polymorphisms: a silent variant
      (c.102G>C), and a 5'-splice site mutation (IVS5+24C>T) in GDPA1 gene identified
      in a five generation Turkish family with autosomal recessive CMT2.

PMID- 19381884
TI  - Identification of a novel GNAS mutation for pseudohypoparathyroidism in a Chinese
      family.
AB  - Pseudohypoparathyroidism (PHP) is a heterogeneous group of diseases characterized
      by hormone resistance to receptors that stimulate adenylate cyclase. PHP-Ia
      patients show specific Gs-alpha protein deficiency, PTH/TSH/gonadotropin
      resistance, and a phenotype characterized by Albright hereditary osteodystrophy
      (AHO). Many heterozygous mutations in the GNAS gene encoding the Gs protein have
      been identified in PHP-Ia. We describe two boys with hypocalcemia and elevated
      serum levels of PTH in a Chinese family. The 13 exons of the GNAS gene were
      amplified using 15 pairs of GNAS-specific primers and analyzed by direct
      sequencing. We found a novel frame shift mutation in exon 11 of the GNAS gene
      identified in both of the two boys and their mother. This report provides another
      example of a Gs-alpha mutation leading to PHP.

PMID- 19381885
TI  - Natural course of benign adrenal incidentalomas in subjects with extra-adrenal
      malignancy.
AB  - Patients with extra-adrenal malignancies are diagnosed increasingly with benign
      adrenal tumors, as well as non-oncology subjects. We aimed to demonstrate the
      natural course of adrenal adenomas in terms of mass size and hormonal status in
      oncology and non-oncology subjects. We also compared the characteristics and
      behavior of adrenal adenomas with adrenal malignancies. In our registry of
      adrenal tumors (n = 335), we prospectively evaluated 29 oncology subjects (EAM+)
      and age, gender, and follow-up duration matched 110 non-oncology subjects (EAM-)
      with adrenal adenomas. Median follow-up was 24 months. We also included 16
      subjects with adrenal malignancies (primary; 3 and metastasis; 13). Tumor size
      was followed-up with CT or MRI at 6th and 12th months and annually in subsequent
      visits. Hormonal assessment was repeated at the 6th month after the initial visit
      and annually in subsequent visits. Initial tumor size, mean increase in tumor
      size, and number of subjects who showed mass enlargement or developed subclinical
      Cushing Syndrome were comparable (P > 0.05) between EAM+ and EAM- groups.
      Subjects with malignant adrenal tumors were older (P = 0.06), had larger tumors
      at presentation (P < 0.001), and showed mass enlargement during a shorter follow
      up duration (P < 0.001). Oncology subjects with adrenal adenomas featured similar
      baseline and follow-up parameters in terms of mass enlargement and development of
      subclinical Cushing Syndrome when compared with non-oncology subjects. Malignant
      adrenal tumors were characterized with large, rapidly growing tumors of older
      ages. Conservative approach can be suggested to oncology subjects for adrenal
      adenomas unless clinical and radiological suspicion of adrenal malignancy is
      present.

PMID- 19381887
TI  - Exacerbation of thyroid associated ophthalmopathy after arterial embolization
      therapy in a patient with Graves' disease.
AB  - A novel treatment approach to Graves' disease (GD), embolization of the thyroid
      gland arteries, is evaluated with respect to its indications and adverse effects.
      We describe an exacerbation of thyroid associated ophthalmopathy (TAO) following
      thyroid artery embolization in a woman with GD and mild stable TAO (NOSPECS
      classification, class I grade a). A 45-year-old woman with GD and inactive TAO,
      in whom thyroid function was stable following blockade of hormone release
      combined with replacement therapy, underwent embolization of three thyroid
      arteries. Initially, there were neither adverse effects nor complications;
      however, the patient developed severe TAO (NOSPECS classification, class IV grade
      b) 3 months after the arterial embolization. Steroid pulse treatments followed by
      total thyroidectomy resulted in improvement of the eye signs and symptoms. The
      clinical course and the serial changes of the thyroglobulin and thyroglobulin
      antibody titers suggested that the destruction of thyroid follicles, induced by
      the arterial embolization, triggered the exacerbation of her TAO. Our experience
      argues for the use of caution when arterial embolization is considered for GD
      patients with even the mildest TAO (NOSPECS classification, class I).

PMID- 19381886
TI  - Hypercoagulability in Cushing's syndrome: the role of specific haemostatic and
      fibrinolytic markers.
AB  - OBJECTIVE: Hypercoagulability is a commonly described complication in patients
      with Cushing's syndrome. Recent clinical studies have indicated various
      abnormalities of coagulation and fibrinolysis parameters which may be related to
      that phenomenon. The aim of this study was to investigate the mechanisms
      underlying the hypercoagulable state in patients with Cushing's syndrome.
      RESEARCH METHODS AND PROCEDURES: A wide range of serum markers involved in the
      processes of blood coagulation and fibrinolysis was measured in a group of 33
      patients with Cushing's syndrome and 31 healthy controls. No participant was
      taking medication which could influence the result or had known diseases, except
      hypertension and diabetes, which could affect blood coagulation or fibrinolysis
      parameters. RESULTS: Patients with Cushing's syndrome had higher levels of
      clotting factors II (P = 0.003), V (P < 0.001), VIII (P < 0.001), IX (P < 0.001),
      XI (P < 0.001) and XII (P = 0.019), protein C (P < 0.001), protein S (P < 0.001),
      C1-inhibitor (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (P =
      0.004). The activity of fibrinolytic markers, plasminogen (P < 0.001),
      antithrombin (P < 0.001) and antithrombin antigen (P = 0.001) was also increased
      in the patient group. CONCLUSION: The study has demonstrated hypercoagulability
      in patients with Cushing's syndrome manifest as increased prothrombotic activity
      and compensatory activation of the fibrinolytic system. We propose the
      introduction of thromboprophylaxis in the preoperative and early postoperative
      periods, combined with a close follow-up in order to prevent possible
      thromboembolic events in patients with Cushing's syndrome.

PMID- 19381888
TI  - Expression of the electrogenic Na+-HCO3--cotransporters NBCe1-A and NBCe1-B in
      rat pancreatic islet cells.
AB  - It was recently proposed that, in rat pancreatic islets, the production of
      bicarbonate accounts for the major fraction of the carbon dioxide generated by
      the oxidative catabolism of nutrient insulin secretagogues. In search of the
      mechanism(s) supporting the membrane transport of bicarbonate, the possible role
      of the electrogenic Na(+)-HCO(3) (-)-cotransporters NBCe1-A and NBCe1-B in rat
      pancreatic islet cells was investigated. Expression of NBCe1-A and NBCe1-B in rat
      pancreatic islet cells was documented by RT-PCR, western blotting, and
      immunocytochemistry. The latter procedure suggested a preferential localization
      of NBCe1-B in insulin-producing cells. Tenidap (3-100 microM), previously
      proposed as an inhibitor of NBCe1-A-mediated cotransport in proximal tubule
      kidney cells, caused a concentration-related inhibition of glucose-stimulated
      insulin secretion. It also inhibited 2-ketoisocaproate-induced insulin release
      and to a relatively lesser extent, the secretory response to L: -leucine. Tenidap
      (50-100 microM) also inhibited the metabolism of D: -glucose in isolated islets,
      increased (22)Na net uptake by dispersed islet cells, lowered intracellular pH
      and provoked hyperpolarization of plasma membrane in insulin-producing cells.
      This study thus reveals the expression of the electrogenic Na(+)-HCO(3) (-)
      cotransporters NBCe1-A and NBCe1-B in rat pancreatic islet cells, and is
      consistent with the participation of such transporters in the process of nutrient
      stimulated insulin secretion.

PMID- 19381890
TI  - A case of Riedel's thyroiditis with pleural and pericardial effusions.
AB  - Riedel's thyroiditis (RT) is a rare type of chronic thyroiditis of unproven
      etiology and definite treatment. It can be associated with retroperitoneal,
      mediastinal, orbital, and hepatic fibrosis. Symptoms arise mainly due to
      compression of neighboring structures. Surgery is usually required for a definite
      diagnosis and decompression to relieve the symptoms. Glucocorticoids and
      tamoxifen are commonly used agents for the pharmacotherapy. We hereby describe
      the development of pleural and pericardial effusions during the clinical course
      of an RT case. A 39-year-old woman suffering from neck compression symptoms was
      admitted to the hospital. After a decompression isthmectomy, RT was diagnosed.
      She responded well to glucocorticoid therapy after surgery. However, symptoms
      reoccurred shortly after glucocorticoid withdrawal and the disease process
      extended to the mediastinum. Tamoxifen was started and the neck and mediastinal
      mass regressed and her symptoms disappeared considerably for more than 6 months.
      However, she was readmitted with severe dyspnea and chest pain. Further
      investigation revealed an exudative pleural and pericardial effusion and
      mediastinal enlargement. A thorough evaluation of the patient's effusions did not
      disclose any specific etiological insult. The patient was symptom-free with a
      considerable reduction of the soft tissue mass and no effusions, and treated
      successfully with colchicine, azathioprine, and glucocorticoids. To the best of
      our knowledge, this is the first case reported in the literature as an RT
      presenting with pleuropericardial effusions.

PMID- 19381889
TI  - Direct effects of eicosapentaenoic and docosahexaenoic acids on phospholipid and
      triglyceride fatty acid pattern, glucose metabolism, 86rubidium net uptake and
      insulin release in BRIN-BD11 cells.
AB  - The long-term metabolic and functional effects of a dietary deprivation of long
      chain polyunsaturated omega3 fatty acids were recently investigated in second
      generation omega3-depleted rats. This study represents the first attempt to
      explore the direct, but not immediate, effects of omega3 fatty acids on insulin
      producing cells. For this purpose, BRIN-BD11 cells were cultured for 24 h in the
      absence or presence of both C20:5omega3 and C22:6omega3 (50 microM each) and,
      thereafter, examined for their phospholipid and triglyceride fatty acid pattern,
      and their metabolic, ionic, and secretory responses to D: -glucose and/or non
      nutrient insulinotropic agents. The prior culture in the presence of the two
      omega3 fatty acids provoked an enrichment of cell lipids in such omega3 fatty
      acids, changes in the phospholipid fatty acid pattern of long-chain
      polyunsaturated omega6 fatty acids as well as saturated and monodesaturated fatty
      acids, and cell steatosis. It minimized the relative increase in D: -[5
      (3)H]glucose utilization and D: -[U-(14)C]glucose oxidation otherwise resulting
      from an increase in the concentration of the hexose from 1.1 to 11.1 mM. It also
      minimized the changes in (86)Rb(+) net uptake otherwise provoked by rises in D: 
      glucose concentration and decreased the absolute values for insulin output. It is
      concluded that the major changes in metabolic, cationic, and secretory behavior
      of the omega3-enriched BRIN-BD11 cells are paradoxically similar to those
      encountered in pancreatic islets from omega3-depleted rats and, in both cases,
      possibly attributable to a phenomenon of lipotoxicity.

PMID- 19381891
TI  - A phase I-II trial of weekly topotecan in the treatment of recurrent cervical
      carcinoma.
AB  - In recent phase III studies, intravenous topotecan (0.75 mg/m(2)) plus cisplatin
      demonstrated significant progression-free and overall-survival benefits in
      patients with advanced and recurrent cervical cancer. However, the regimen
      demonstrated clinically significant myelotoxicity. The current study was
      undertaken to examine the safety, tolerability, and efficacy of weekly bolus
      topotecan in patients with advanced or metastatic disease. All patients had
      biopsy-confirmed disease not amenable to radiation treatment or surgery. Lesions
      were measurable bidimensionally, and patients had adequate hematologic, hepatic,
      and renal function. Patients received 3.5 mg/m(2) topotecan intravenously on days
      1, 8, and 15 of a 28-day cycle. If no grade 3 or 4 hematologic toxicities
      occurred, the dose was escalated to 4 mg/m(2) in the third cycle. Safety,
      tolerability, and response rates were the primary endpoints. In addition to
      weekly hematologic assessments, Eastern Cooperative Oncology Group status was
      evaluated monthly, and tumor response was evaluated every alternate cycle. Twenty
      patients were enrolled and evaluated for toxicity and tumor response. Grade 3
      toxicity occurred in 8/48 (17%) treatment cycles. There was only one drug-related
      adverse toxicity that required a dose reduction. Grade 1/2 hematologic toxicities
      were rare and only accounted for 1 (2%) of the dose delays (1 week). Two (10%)
      patients achieved stable disease for a mean of 5.3 months. The weekly bolus
      topotecan regimen used in the current study was well tolerated. Future phase II
      studies of weekly bolus topotecan in combination with cisplatin in this patient
      population may be warranted.

PMID- 19381892
TI  - Platelet count: association with prognosis in lung cancer.
AB  - Lung cancer (LC) is now the leading cause of cancer mortality in the world,
      therefore it would be useful to identify prognostic factors to determine patient
      outcome. The objective of this study is to evaluate the usefulness of platelet
      counts at the time of diagnosis as a prognostic factor. A retrospective study of
      patients with histological diagnostic evidence of LC was carried in our catchment
      area over a 3-year period. Survival adjusted for other factors was assessed
      according to the platelet count at the time of diagnosis. Patients with platelet
      levels within the reference range (RR) (135000-381000/microl) were divided into
      two groups, between 135000-258000/microl and 258000-381000/microl. A third group
      was made up of patients with platelet counts over 381000/microl. Adjusted
      survival was analysed using Cox regression models. Patients with high platelets
      have a 37% worse survival than those with a platelet level within the RR, but
      lower than 258000/microl. When tumour stage is included in the covariates,
      platelet levels are no longer an independent survival factor. In conclusion,
      platelet levels at the time of diagnosis could be a useful prognostic factor in
      LC.

PMID- 19381893
TI  - Comparative proteome analysis of human adenocarcinoma.
AB  - This study was designed to use comparative proteomics technology to find the
      differentially expressed proteins between human lung adenocarcinoma and paired
      normal tumor-adjacent lung tissues. The total proteins of 20 human lung
      adenocarcinoma tissues and paired normal tumor-adjacent lung tissues were
      separated by means of immobilized pH gradient-based two-dimensional gel
      electrophoresis (2-DE) and Coomassie Blue staining. The differentially expressed
      proteins were analyzed with image analysis software and then identified by matrix
      assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF
      MS) and quadrupole time of flight mass spectrometry (Q-TOF-MS/MS). (1) Well
      resolved, highly reproducible 2-DE patterns of human lung adenocarcinoma and
      paired normal tumor adjacent lung tissues were obtained. (2) PDQUEST 2D image
      analysis software was used to analysis 20 cases of lung adenocarcinoma and paired
      normal lung tissues, 1006 +/- 54 spots were matched among tumor tissues and
      normal lung tissues. Twenty-eight differentially expressed spots were screened.
      (3) Twenty non-redundant differentially expressed proteins were identified by
      mass spectrometry, thirteen proteins were up-regulated, and seven proteins were
      down-regulated, some proteins were involved in the regulation of cell signal
      transduction or metabolized enzyme of cell. (4) To validate the results screened
      by proteome research, immunohistochemistry was used to validate several lung
      adenocarcinoma differentially expressed proteins including 14-3-3 sigma, annexin
      1, and manganese superoxide dismutase. The results showed that these three
      proteins were really differentially expressed between lung adenocarcinoma and
      paired normal lung tissues. These results will provide scientific foundation and
      new clue for the research of human lung adenocarcinoma.

PMID- 19381917
TI  - Monitoring DNA breaks in optically highlighted chromatin in living cells by laser
      scanning confocal microscopy.
AB  - The recognition and repair of DNA lesions occurs within a chromatin environment.
      Genetically tagging fluorescent proteins to DNA damage response proteins has
      provided spatial and temporal details concerning the establishment of biochemical
      subnuclear regions geared toward metabolizing genomic lesions. A specific marker
      for chromatin regions containing DNA breaks is required to study the initial
      dynamic structural changes in chromatin when DNA breaks occur. Here we present
      the experimental protocols used to investigate the dynamics of chromatin
      structure immediately after the simultaneous photoactivation of PAGFP-tagged core
      histone H2B and introduction of DNA breaks using UVA laser microirradiation on a
      laser scanning confocal microscope.

PMID- 19381919
TI  - Analysis of DNA topology in yeast chromatin.
AB  - Topology of closed circular DNA is affected by its packaging into nucleosomes and
      potentially by alteration of nucleosome structure. Changes in topology that
      reflect alterations in chromatin structure can be measured and quantified using
      closed circular plasmids from living yeast. Here we describe detailed protocols
      for measuring DNA topology in yeast chromatin.

PMID- 19381918
TI  - Preparation and analysis of uniquely positioned mononucleosomes.
AB  - Short DNA fragments containing single, uniquely positioned nucleosome cores have
      been extensively employed as simple model experimental systems for analysis of
      many intranuclear processes, including binding of proteins to nucleosomes,
      transcription, DNA repair and ATP-dependent chromatin remodeling. In many cases
      such simple model templates faithfully recapitulate numerous important aspects of
      these processes. Here we describe several recently developed procedures for
      obtaining and analysis of mononucleosomes that are uniquely positioned on 150-600
      bp DNA fragments.

PMID- 19381920
TI  - Drug-induced premature chromosome condensation (PCC) protocols: cytogenetic
      approaches in mitotic chromosome and interphase chromatin.
AB  - Chromosome analysis is a fundamental technique for cytogenetic studies.
      Chromosomes are conventionally prepared from mitotic cells arrested by colcemid
      block protocol. However, obtaining the mitotic chromosomes is often hampered
      under several circumstances. As a result, cytogenetic analysis will be sometimes
      difficult or even impossible in such cases. Premature chromosome condensation
      (PCC) is an alternative method that has proved to be a unique and useful way in
      chromosome analysis. Usually, PCC has been achieved following cell fusion
      mediated either by fusogenic viruses or by polyethylene glycol (cell-fusion PCC),
      but the cell-fusion PCC has several drawbacks. The novel drug-induced PCC using
      protein phosphatase inhibitors was introduced about 10 years ago. This method is
      much simple and easy even than the conventional mitotic chromosome preparation
      using colcemid block protocol and obtained PCC index (equivalent to mitotic index
      for metaphase chromosome) is much higher. Furthermore, this method allows the
      interphase chromatin to be condensed and visualized like mitotic chromosomes,
      thus opened the way for chromosome analysis not only in metaphase chromosomes but
      also in interphase chromatin. The drug-induced PCC has therefore proven the
      usefulness in cytogenetics and other cell biology fields.

PMID- 19381921
TI  - Visualization of the expression of HMGN nucleosomal binding proteins in the
      developing mouse embryo and in adult mouse tissues.
AB  - Visualization of the expression pattern of specific proteins during development
      and in adult tissues provides important clues as to their possible role in
      various cellular processes. Mouse is the organism of choice for obtaining
      information on gene expression patterns in higher eukaryotes. This chapter
      describes the protocols we utilized to visualize Hmgn transcripts and HMGN
      proteins in mouse tissues. HMGN are chromatin-binding proteins that affect
      chromatin structure and function and play a role in cellular differentiation.

PMID- 19381922
TI  - DNA methyltransferase probing of chromatin structure within populations and on
      single molecules.
AB  - Non-invasive methods for mapping chromatin structure are necessary for creating
      an accurate view of genome function and dynamics in vivo. Ectopic induction of
      cytosine-5 DNA methyltransferases (C5 MTases) in Saccharomyces cerevisiae is a
      powerful technique for probing chromatin structure with minimal disruption to
      yeast physiology. Accessibility of MTases to their cognate sites is impaired
      based on the strength and span of the protein-DNA interaction to be probed.
      Methylated cytosines that resist chemical deamination are detected positively by
      the PCR-based technique of bisulfite genomic sequencing. PCR amplicons can be
      sequenced directly yielding an average m(5)C frequency or accessibility of each
      target site within the population, a technique termed methyltransferase
      accessibility protocol (MAP). More recently, the sequencing of cloned molecules
      in MAP for individual templates (MAPit) enables assignment of the methylation
      status of each target site along a continuous DNA strand from a single cell. The
      unique capability to score methylation at multiple sites in single molecules
      permits detection of inherent structural variability in chromatin. Here, MAPit
      analysis of the repressed and induced PHO5 promoter of budding yeast, using a C5
      MTase with dinucleotide recognition specificity, reveals considerable cell-to
      cell heterogeneity in chromatin structure. Substantial variation is observed in
      the extent to which the MTase gains entry to each of the nucleosomes positioned
      at PHO5, suggesting differences in their intrinsic thermodynamic stability in
      vivo. MAPit should be readily adaptable to the analysis of chromatin structure
      and non-histone protein-DNA interactions in a variety of model systems.

PMID- 19381923
TI  - In vivo chromatin decondensation assays: molecular genetic analysis of chromatin
      unfolding characteristics of selected proteins.
AB  - Of critical importance to many of the events underlying transcriptional control
      of gene expression are modifications to core and linker histones that regulate
      the accessibility of trans-acting factors to the DNA substrate within the context
      of chromatin. Likewise, control over the initiation of DNA replication, as well
      as the ability of the replication machinery to proceed during elongation through
      the multiple levels of chromatin condensation that are likely to be encountered,
      is almost certain to involve the creation of chromatin accessibility. In the
      latter case in particular, chromatin access will likely need to be a transient
      event so as to prevent total genomic unraveling of the chromatin that would be
      deleterious to cells. While there are many molecular and biochemical approaches
      in use to study histone changes and their relationship to transcription and
      chromatin accessibility, few techniques exist that allow a molecular dissection
      of the events underlying DNA replication control as it pertains to chromatin
      changes and accessibility. In this review, we outline a novel experimental
      strategy for addressing the ability of specific proteins to induce large-scale
      chromatin unfolding (decondensation) in vivo upon site-specific targeting to an
      engineered locus. We have used this system successfully to directly address the
      ability of DNA replication proteins to create chromatin accessibility and have
      incorporated modifications to the basic approach that allow for a molecular
      genetic analysis of the players involved in causing chromatin decondensation by a
      protein of interest. Here, we briefly describe the nature of the experimental
      system, its history, and a basic protocol for using the system. Alternative
      approaches involving co-transfections, concurrent drug treatments, and analysis
      of co-localizing histone modifications are also addressed, which are useful for
      extending basic findings to physiological mechanisms.

PMID- 19381924
TI  - Detecting ATM-dependent chromatin modification in DNA damage and heat shock
      response.
AB  - The ataxia telangiectasia-mutated gene product (ATM), whose loss of function is
      responsible for ataxia telangiectasia (A-T), is a protein kinase that interacts
      with several substrates and is implicated in mitogenic signal transduction,
      chromosome condensation, meiotic recombination, cell-cycle control and telomere
      maintenance (Pandita, Expert Reviews in Molecular Medicine 5:1-21, 2003; Pandita,
      Oncogene 21:611-618, 2002; Matsuoka et al., Science 316:1160-1166, 2007). The ATM
      protein kinase is primarily activated in response to DNA double-strand breaks
      (DSBs) caused by ionizing radiation (IR) or radiomimetic drugs (Pandita et al.,
      Oncogene 19:1386-1391, 2000). ATM is also activated by heat shock, which occurs
      independent of DNA damage (Hunt et al., Can Res 69:3010-3017, 2007). ATM is
      observed at the sites of DNA damage, where it is autophosphorylated and is
      dissociated from its non-active dimeric form to the active monomeric form
      (Bakkenist and Kastan, Nature 421:499-506, 2003). The ATM protein appears to be a
      part of the sensory machinery that detects DSBs during meiosis or mitosis, or
      breaks consequent to the damage by free radicals. Recent studies support the
      argument that ATM activation is regulated by chromatin modifications (Gupta, Mol
      Cell Biol 25:5292-5305, 2005). This review summarizes the multiple approaches
      used to discern the role of ATM in chromatin modification in response to DNA
      damage as well as heat shock.

PMID- 19381925
TI  - Non-radioactive assay methods for the assessment of telomerase activity and
      telomere length.

PMID- 19381926
TI  - ChIP-on-Chip Analysis methods for Affymetrix Tiling Arrays.
AB  - ChIP-Chip microarray data analysis is a multi-step approach that requires several
      different applications to progress from the initial stages of raw data analysis
      to the identification and characterization of ChIP-binding sites. There are
      multiple approaches to data analysis and several applications available for each
      stage of the analysis pipeline. Each application must be evaluated for its
      suitability for the particular experiment as well as the researcher's computer
      background. This chapter is a review of the commonly available applications for
      Affymetrix ChIP-Chip data analysis, as well as the general workflow of a ChIP
      Chip analysis approach. The purpose of the chapter is to allow the researcher to
      better select the appropriate applications and provide them with the direction
      necessary to proceed with a ChIP-Chip analysis.

PMID- 19381927
TI  - ChIP on chip assays: genome-wide analysis of transcription factor binding and
      histone modifications.
AB  - Deregulation of transcriptional activity of many genes has been causatively
      linked to human diseases including cancer. Altered patterns of gene expression in
      normal and cancer cells are the result of inappropriate expression of
      transcription factors and chromatin-modifying proteins. Chromatin
      immunoprecipitation assay is a well-established tool for investigating the
      interactions between regulatory proteins and DNA at distinct stages of gene
      activation. ChIP coupled with DNA microarrays, known as ChIP on chip, allow us to
      determine the entire spectrum of in vivo DNA-binding sites for a given protein.
      This has been of immense value because ChIP on chip assays can provide a snapshot
      of the transcriptional regulatory mechanisms on a genome-wide scale. This article
      outlines the general strategies used to carry out ChIP-chip assays to study the
      differential recruitment of regulatory molecules based on the studies conducted
      in our lab as well as other published protocols.

PMID- 19381928
TI  - Chromatin immunoprecipitation assays: analyzing transcription factor binding and
      histone modifications in vivo.
AB  - Studies in the past decade have shown that differential gene expression depends
      not only on the binding of specific transcription factors to discrete promoter
      elements but also on the epigenetic modification of the DNA as well as histones
      associated with the promoter. While techniques like electrophoretic mobility
      shift assays could detect and characterize the binding of specific transcription
      factors present in cell lysates to DNA sequences in in vitro binding conditions,
      they were not effective in assessing the binding in intact cells. Development of
      chromatin immunoprecipitation technique in the past decade enabled the analysis
      of the association of regulatory molecules with specific promoters or changes in
      histone modifications in vivo, without overexpressing any component. ChIP assays
      can provide a snapshot of how a regulatory transcription factor affects the
      expression of a single gene or a variety of genes at the same time. Availability
      of high-quality antibodies that recognizes histones modified in a specific
      fashion further expanded the use of ChIP assays to analyze even minute changes in
      histone modification and nucleosomes structure. This chapter outlines the general
      strategies and protocols used to carry out ChIP assays to study the differential
      recruitment of transcription factors as well as histone modifications.

PMID- 19381929
TI  - Detection of histone H3 phosphorylation in cultured cells and tissue sections by
      immunostaining.
AB  - Growth factor stimulation results in phosphorylation of histone H3 at ser 10 and
      this correlated with expression of immediate early genes suggesting that this
      phosphorylation is associated with transcriptional activation. Although Western
      immunoblot analysis allows the detection of protein modifications in histones, in
      order to determine the localization of histones during different phases of cell
      cycle or during treatment of cells with different drugs we have to use
      immunohistochemistry. The protocol described here allows the detection of
      phosphorylated histones in tissue-cultured cells and tissue sections by
      fluorescent or bright-field immunostaining analysis. Here we used a serine 10
      specific P-histone H3 antibody to determine the localization of this
      phosphoprotein in an asynchronously growing H4 glioma cell line and brain
      sections. It has been shown that long-term potentiation (LTP) is associated with
      gene transcription, and histone acetylation plays a major role in LTP formation
      (Wood et al., Learn Mem 13:241-244, 2006; Wood et al., Hippocampus 15:610-621,
      2005; Alarcon et al., Neuron 42:947-959, 2004; Korzus et al., Neuron 42:961-972,
      2004). Stimulus-induced phosphorylation of histone H3 at serine 10 has also been
      implicated in hippocampal neurons and striatal neurons (Li et al., J Neurochem
      90:1117-1131, 2004; Crosio et al., J Cell Sci 116:4905-4914, 2003). Co-staining
      with a cell-specific antibody will allow us to determine the type of cells that
      show activation of histone phosphorylation in the brain.

PMID- 19381930
TI  - In vitro and in vivo assays for studying histone ubiquitination and
      deubiquitination.
AB  - Posttranslational histone modifications play important roles in regulating
      chromatin structure and function (Martin and Zhang, Nat Rev Mol Cell Biol 6:838
      849, 2005; Jenuwein and Allis, Science 293:1074-1080, 2001). One example of such
      modifications is histone ubiquitination, which occurs predominately on H2A and
      H2B. Recent studies have highlighted important regulatory roles of H2A
      ubiquitination in Polycomb group proteins-mediated gene silencing (Wang et al.,
      Nature 431:873-878, 2004; Joo et al., Nature 449:1068-1072, 2007) and H2B
      ubiquitination in transcription, H3 methylation, and DNA methylation (Zhang,
      Genes Dev 17:2733-2740, 2003; Sun and Allis, Nature 418:104-108, 2002; Sridhar et
      al., Nature 447:735-738, 2007). Here we describe methods for in vitro histone
      ubiquitination and deubiquitination assays. We also describe approaches to
      investigate the in vivo function of a putative histone ubiquitin ligase and
      deubiquitinase. These experimental procedures are largely based on our studies in
      mammalian cells. These methods should provide useful tools for studying this
      bulky histone modification.

PMID- 19381931
TI  - Analysis of reconstituted chromatin using a solid-phase approach.
AB  - Complex experimental strategies involving in vitro reconstituted chromatin or
      simple chromatin interaction studies are much facilitated by immobilizing the
      nucleosomal arrays to paramagnetic beads. Chromatin-containing beads can be
      retrieved from a reaction mix solution on a magnet fast and quantitatively,
      effectively separating bound, loosely attached and unbound components
      efficiently. This chapter details a convenient strategy for immobilization of
      linear plasmid DNA on streptavidin-coated beads, the reconstitution of chromatin
      on such beads and some fundamental handling procedures.

PMID- 19381932
TI  - Histone deacetylase activity assay.
AB  - Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl
      groups from the epsilon-amino groups of conserved lysine residues in the amino
      terminal tail of histones. In humans, there are 18 potential deacetylase enzymes
      that are responsible for the removal of acetyl groups and maintenance of the
      equilibrium of lysine acetylation on histones. Like most histone modification
      enzymes, accumulating evidence suggests that many, if not all, HDACs can also
      modify non-histone proteins. The focus of this article is to provide up-to-date,
      easy to follow, approaches and techniques specifically for the assay of HDAC
      enzymatic activities.

PMID- 19381933
TI  - Histone chaperone as coactivator of chromatin transcription: role of acetylation.
AB  - Histone chaperones are a group of histone-interacting proteins, involved in
      several important cellular functions. These chaperones are essential to
      facilitate ordered assembly of nucleosomes, both in replication dependent and
      independent manner. Replication independent function of histone chaperone is
      necessary for histone eviction during transcriptional initiation and elongation.
      In this chapter we have discussed a method to evaluate the role of histone
      chaperone NPM1 (the only known chaperone to get acetylated with functional
      consequence) in the transcriptional activation which is acetylation dependent.

PMID- 19381934
TI  - In vitro histone demethylase assays.
AB  - Histone methylation plays important roles in chromatin structure, transcription,
      and epigenetic state of the cell. Tremendous discoveries recently demonstrated
      that methylation mark is not static but is dynamically regulated by both histone
      methyltransferases and the histone demethylases. Two families of histone
      demethylases have been identified to remove methyl groups from lysine side chain
      through different reaction mechanisms in presence of distinct cofactors. Amine
      oxidase LSD1 family requires flavin adenine dinucleotide (FAD) whereas
      dioxygenase Jmjc domain-containing proteins family relies on Fe(II) and alpha
      ketoglutarate. Identification of these enzymes opened a new era in understanding
      how chromatin dynamic is regulated and further understanding the regulation of
      these enzymes will provide significant insights into fundamental mechanisms of
      many biological processes and human diseases. This chapter describes different
      assay conditions and detection methods for different family of histone
      demethylases. We also summarize step-by-step protocols for purification and
      preparation of various histone substrates for histone demethylase assays.

PMID- 19381935
TI  - Biochemical analysis of arginine methylation in transcription.
AB  - Protein arginine methylation has emerged as an important mechanism for regulating
      the functions of proteins involved in diverse aspects of gene regulation such as
      transcriptional activation and repression, mRNA processing and nuclear
      cytoplasmic shuttling. This modification is catalyzed by the PRMT family of
      enzymes which utilize intracellular S-adenosyl methionine as a cofactor to
      dimethylate-specific arginines found within many target proteins.The
      establishment of in vitro biochemical assays as well as the development of
      modification-specific antibodies, and more recently mass spectrometry, have
      increased our understanding of the mechanism of catalysis of the PRMT family of
      enzymes. In the following discussion, we present some of the more commonly used
      in vivo and in vitro techniques which can be utilized to study the mechanism of
      arginine methylation and its role in transcription.

PMID- 19381936
TI  - Investigation of genomic methylation status using methylation-specific and
      bisulfite sequencing polymerase chain reaction.
AB  - Epigenetic modification plays a central role in the regulation of gene expression
      and therefore in the development of disease states. In particular, genomic
      methylation of cytosines within CpG dinucleotides is crucial to development, gene
      silencing and chromosome inactivation. Importantly, aberrant methylation profiles
      of various genes are associated with cancer and potentially autoimmune disease,
      brain-related disease, diabetes and heart disease. Various methods are available
      for the detection and quantification of methylation in a given sample. Most of
      these methods rely upon bisulfite conversion of DNA, which converts unmethylated
      cytosines to uracil, while methylated cytosines remain as cytosines. Methylation
      specific amplification of DNA can be used to detect methylation at one or more
      (typically up to about 4) CpG sites by using primers specific to either
      methylated or unmethylated DNA. Alternatively, amplification of both methylated
      and unmethylated DNA followed by sequencing can be used to detect methylation
      status at multiple CpG sites. The following chapter provides protocols for
      bisulfite conversion of DNA, methylation-specific PCR and bisulfite sequencing
      PCR.

PMID- 19381937
TI  - In vitro replication assay with mammalian cell extracts.
AB  - Regulatory mechanisms for DNA replication are crucial to the control of the cell
      cycle in eukaryotic cells. One of the widely used assays to understand the
      complex mammalian replication system is the cell-free in vitro replication assay
      (IVRA). IVRA can provide a snapshot of the regulatory mechanisms controlling
      replication in higher eukaryotes by using a single plasmid, pEPI-1. This chapter
      outlines the general strategies and protocols used to perform IVRA to study the
      differential recruitment of replication factors either independently or in
      combination, based on the experience in studying the role of prohibitin in
      replication as well as other published protocols. This method can be employed to
      identify not only proteins that assist replication but also proteins that inhibit
      replication of mammalian genome.

PMID- 19381938
TI  - Analysis of genomic aberrations using comparative genomic hybridization of
      metaphase chromosomes.
AB  - Comparative genomic hybridization (CGH) allows the global screening of copy
      number aberrations within a sample. Specifically, large (>20 mb) deletions and
      amplifications are detected, which are likely to indicate regions harboring tumor
      suppressor and oncogenes. CGH involves the extraction of test and reference
      (karyotypically normal) DNA. These samples are whole-genome amplified by DOP-PCR
      and then differentially labeled with fluorophores via nick translation. Test and
      reference samples are competitively hybridized to normal metaphase chromosomes.
      The relative amount of each DNA that binds to a chromosomal locus is indicative
      of the abundance of that DNA. Thus, if a chromosomal region is amplified, the
      test DNA will outcompete the reference DNA for binding and fluorescence will
      indicate amplification. Conversely, if a region is deleted, more reference DNA
      will bind and fluorescence will indicate a deletion. The following chapter
      outlines the protocols used for CGH analysis of metaphase chromosomes. These
      protocols include metaphase chromosome slide preparation, DNA extraction (from
      blood, cell lines and microdissected formalin-fixed paraffin-embedded tissue),
      DOP-PCR, nick translation, in situ hybridization and fluorescence microscopy and
      image analysis.

PMID- 19381939
TI  - Detection of DNA damage induced by topoisomerase II inhibitors, gamma radiation
      and crosslinking agents using the comet assay.
AB  - The comet assay is a simple gel electrophoresis method for visualizing and
      quantifying DNA damage. The comet assay is sensitive and reproducible and can be
      used to detect single-strand DNA breaks, double-strand DNA breaks, protein
      associated DNA strand breaks and DNA crosslinks. The comet assay uses fluorescent
      DNA-binding dyes to detect both damaged DNA that resides in the tail region and
      undamaged DNA that is retained in the head region following gel electrophoresis.
      This assay is a single cell-based assay and thus is highly adaptable for
      measuring DNA damage in clinical samples. Furthermore, unlike other assays the
      detection of DNA damage is not dependent on the random incorporation of
      radiolabeled nucleotides. Again this can be problematic with clinical samples as
      proliferation rates are often slow and culturing of primary patient specimens for
      48 h required to randomly label DNA is often not possible. In this chapter we
      will outline the comet assay for the detection of DNA damage induced by
      topoisomerase II inhibitors, cross-linking agents and gamma radiation.

PMID- 19381940
TI  - Cytometric analysis of DNA damage: phosphorylation of histone H2AX as a marker of
      DNA double-strand breaks (DSBs).
AB  - Phosphorylation of histone H2AX on Ser 139 is a sensitive reporter of DNA damage,
      particularly if the damage involves induction of DNA double-strand breaks (DSBs).
      Phosphorylated H2AX has been named gammaH2AX and its presence in the nucleus can
      be detected immunocytochemically. Multiparameter analysis of gammaH2AX
      immunofluorescence by flow or laser-scanning cytometry allows one to measure
      extent of DNA damage in individual cells and to correlate it with their position
      in the cell cycle and induction of apoptosis. This chapter presents the protocols
      and outlines applications of multiparameter cytometry in analysis of H2AX
      phosphorylation as a reporter of the presence of DSBs.

PMID- 19381941
TI  - Methods to study transcription-coupled repair in chromatin.
AB  - Transcription-coupled repair (TCR) is a sub-pathway of nucleotide excision repair
      that allows for the enhanced repair of the transcribed strand of active genes. A
      classical method to study DNA repair in vivo consists in the molecular analysis
      of UV-induced DNA damages at specific loci. Cells are irradiated with a defined
      dose of UV light leading to the formation of DNA lesions and incubated in the
      dark to allow repair. About 90% of the photoproducts consist of cyclobutane
      pyrimidine dimers, which can be cleaved by the DNA nicking activity of the T4
      endonuclease V (T4endoV) repair enzyme. Strand-specific repair in a suitable
      restriction fragment is determined by alkaline gel electrophoresis followed by
      Southern blot transfer and indirect end-labeling using a single-stranded probe.
      Recent approaches have assessed the role of transcription factors in TCR by
      analyzing RNA polymerase II occupancy on a damaged template by chromatin
      immunoprecipitation (ChIP). Cells are treated with formaldehyde in vivo to cross
      link proteins to DNA and enrichment of a protein of interest is done by
      subsequent immunoprecipitation. Upon reversal of the protein-DNA cross-links, the
      amount of coprecipitated DNA fragments can be detected by quantitative PCR. To
      perform ChIP on UV-damaged templates, we included an in vitro photoreactivation
      step prior to PCR analysis to ensure that all precipitated DNA fragments serve as
      substrates for the PCR reaction. Here, we provide a detailed protocol for both
      the DNA repair analysis and the ChIP approaches to study TCR in chromatin.

PMID- 19381942
TI  - Preparation of chromatin assembly extracts from preblastoderm Drosophila embryos.
AB  - A rigorous biochemical analysis of chromatin structure and function requires the
      assembly of chromatin in vitro. A useful alternative to reconstituting
      nucleosomal arrays from pure or recombinant histones by salt gradient dialysis is
      the assembly of more complex chromatin from assembly extracts under physiological
      conditions. Extracts from preblastoderm embryos have proven to be particularly
      efficient, due to the presence of large stores of native complexes of histones,
      histone chaperones and ATP-dependent nucleosome spacing factors. The resulting
      chromatin is an excellent approximation of physiological chromatin in vivo. This
      chapter describes the preparation of chromatin assembly extracts and the
      chromatin assembly reaction.

PMID- 19381943
TI  - Identification of tumor-associated antigens as diagnostic and predictive
      biomarkers in cancer.
AB  - Many studies demonstrated that cancer sera contain antibodies which react with
      autologous cellular antigens generally known as tumor-associated antigens (TAAs).
      In our laboratories, the approach used in the identification of TAAs has involved
      initially examining the sera of cancer patients using extracts of tissue culture
      cells as source of antigens in Western blotting and by indirect
      immunofluorescence on whole cells. With these two techniques, we identify sera
      which have high-titer fluorescent staining or strong signals to cell extracts on
      Western blotting and subsequently use these sera as probes in immunoscreening
      cDNA expression libraries, and also in proteomic approaches to isolate and
      identify targeted antigens which might potentially be involved in malignant
      transformation. In this manner, several novel TAAs including HCC1, p62, p90, and
      others have been identified. In extension of these studies, we evaluate the
      sensitivity and specificity of different antigen-antibody systems as markers in
      cancer in order to develop "tumor-associated antigen array" systems for cancer
      diagnosis, cancer prediction, and for following the response of patients to
      treatment.

PMID- 19381944
TI  - Autoantibodies against cancer antigens.
AB  - With the identification of tumor antigens, the host immune response to various
      types of cancers can now be studied with a high degree of specificity in large
      cohorts of patients, in the hope of correlating immunity with clinical events and
      defining immunotherapeutic strategies. Several antigens, such as NY-ESO-1, p53,
      or SOX2, have attracted attention because of their frequent spontaneous
      immunogenicity in cancer patients, notably in their ability to induce humoral
      responses. We describe in this chapter a simple implementation of a serological
      monitoring platform for autoantibody measurement in cancer patients, from
      production of recombinant antigens to ELISA testing and interpretation.

PMID- 19381945
TI  - Discovery of antibody biomarkers using protein microarrays of tumor antigens
      cloned in high throughput.
AB  - Development of humoral and cellular immunity against self-cellular proteins in
      cancer patients is a phenomenal observation. The ability of immune system to
      sense the presence of the disease and to fight of the disease by generating
      autoantibodies against tumor antigens makes it a natural biosensor. Several
      screening technologies have been employed for the identification of tumor
      specific antibodies in cancer patients. We have developed a multidimensional
      approach for the identification of diagnostic antigens that utilizes a
      combination of high-throughput antigen cloning and protein microarray-based
      serological detection of complex panels of antigens by exploiting the serum
      autoantibody repertoire directed toward tumor-associated antigens in cancer
      patients. Furthermore, validation of these antigens by different bioinformatics
      and biological approaches will reveal the diagnostic/prognostic utility of these
      antigens for personalized immunotherapy.

PMID- 19381946
TI  - Analysis of glycans on serum proteins using antibody microarrays.
AB  - Antibody arrays can be employed for the profiling glycan structures on proteins.
      Antibody arrays capture multiple, specific proteins directly from biological
      samples (such as serum), and lectin and glycan-binding antibodies probe the
      levels of specific glycans on the captured proteins. We use a practical method of
      partitioning microscope slides to enable the convenient processing of many
      detection reagents or samples. A critical first step in the procedure is the
      chemical derivatization of the glycans on the spotted capture antibodies, which
      prevents lectin binding to those glycans. We describe those methods along with
      the methods for preparing and treating serum samples, running the experiments,
      and designing and interpreting the experiments.

PMID- 19381947
TI  - Glycoproteomic analysis by two-dimensional electrophoresis.
AB  - Changes in N-linked glycosylation are known to occur during the development of
      cancer. For example, increased branching of oligosaccharides has been associated
      with metastasis and has been correlated to tumor progression in human cancers of
      the breast, colon, and melanomas. Increases in core fucosylation have also been
      associated with the development of hepatocellular carcinoma (HCC). To a large
      extent, the proteins to which these N-linked glycans are attached have been
      unknown. However, with the advent of sensitive glycan analysis and proteomic
      technologies, the ability to comprehensively identify all the fucosylated
      proteins in a given population is now a possibility. This method, generally
      referred to as targeted glycoproteomics, is shown as applied to the detection of
      proteins present in the fucosylated proteome of a liver cancer cell line but is
      generally enough to be applied in many other situations.

PMID- 19381948
TI  - All-liquid separations, protein microarrays, and mass spectrometry to interrogate
      serum proteomes: an application to serum glycoproteomics.
AB  - Disease-related changes in serum proteins are reasonable targets for early
      detection particularly due to the noninvasive approach in obtaining samples.
      Glycoproteins specifically have been implicated in a variety of disease types
      ranging from immune diseases to cancers. High-throughput screening methods that
      can assess glycosylation states of all serum proteins in normal and diseased
      sample groups can facilitate early detection as well as shed light on disease
      progression mechanisms. Outlined here is a combination of liquid separation,
      protein microarray, and mass spectrometry approach to highlight candidate
      proteins involved in diseases through glycosylation mechanisms.

PMID- 19381949
TI  - Reverse-phase protein microarrays for theranostics and patient tailored therapy.
AB  - Analysis of the genome provides important information about the somatic genetic
      changes existing in the tissue; however, it is the proteins that do the work of
      the cell. Diseases such as cancer are caused by derangements in cellular protein
      molecular networks and cell signaling pathways. These pathways contain a large
      and growing collection drug targets, governing cellular survival, proliferation,
      invasion, and cell death. The clinical utility of reverse-phase protein
      microarrays (RPPA), a new technology invented in our laboratory, lies in its
      ability to generate a functional map of known cell signaling networks or pathways
      for an individual patient obtained directly from a biopsy specimen. Coupled with
      laser capture microdissection (LCM), the RPPA platform, the entire cellular
      proteome is immobilized on a substratum with subsequent immunodetection of the
      total levels and phosphorylated, or activated, state of cell signaling proteins.
      The results of which pathways are "in use" can then be correlated with biological
      and clinical information and serve as both a diagnostic and a therapeutic guide,
      thus providing a "theranostic" endpoint.

PMID- 19381950
TI  - Serum proteomics using mass spectrometry.
AB  - The identification and eventual application of tumor markers in cancer screening,
      early detection, diagnosis, and prognosis is a continuing focus of significant
      translational cancer research. While many new candidate markers have been
      discovered and at least partly characterized, very few have found widespread
      clinical application limited presently to the use of CA-125 in ovarian cancer,
      CEA, primarily in colon cancer, and PSA in prostate cancer screening and patient
      monitoring. The rapidly emerging field of cancer genomics and proteomics, and
      their clinical translation as "molecular diagnosis" and "molecular medicine" are
      already beginning to transform the field, and the accelerating growth of
      information and technology in this research area will undoubtedly transform the
      field of tumor markers and their application in the near future leading to
      improved molecular tools for cancer diagnosis, prognosis, and treatment and
      ultimately, to the emergence of novel and more effective cancer therapies,
      including improved approaches for immunotherapy and cancer prevention strategies.
      Toward this goal, herein are described detailed methods and workflows for mass
      spectrometry-based biomarker discovery in serum/plasma utilizing two
      complementary approaches - matrix-assisted laser desorption ionization time of
      flight (MALDI-TOF) and nanoflow reversed-phase liquid chromatography (RPLC)
      tandem mass spectrometry (MS/MS). These discovery workflows incorporate both
      abundant protein depletion and sample fractionation upstream of analytical mass
      spectrometry to optimize the identification and quantitation of lower abundant
      species.

PMID- 19381951
TI  - Hormones as biomarkers: practical guide to utilizing luminex technologies for
      biomarker research.
AB  - Hormones are chemical messengers produced in one part of the body and released
      into the blood to trigger or regulate particular functions of the body in another
      part. Hormone actions vary widely, but can include stimulation or inhibition of
      growth, induction or suppression of apoptosis, activation or inhibition of the
      immune system, regulating metabolism, and preparation for a new activity or phase
      of life. There is a growing interest in the role that hormones may play in the
      development and progression of various cancers. Recent research suggests that
      hormone levels may explain differences in risk for some of the most commonly
      diagnosed cancers, including breast, ovarian, and others; however, additional
      studies utilizing novel hormone measurement technologies are needed to
      investigate the roles of common hormones in cancer. Increasing our understanding
      of the role of hormones and other biomarkers in the etiology and the course of
      different cancers has a great potential to facilitate the development of new
      treatment modalities. This chapter provides an overview on multiplexing xMAP
      technology by Luminex (Austin, TX) that can be used for simultaneous analysis of
      several biologic markers, e.g., hormones. The xMAP immunoassay technology
      combines the principle of a sandwich ELISA with the fluorescent-bead-based
      technology allowing individual and multiplex analysis of up to 100 different
      analytes in a single microtiter well. Serum assay described in the methods
      section is performed in 96-well microplate format according to the protocol
      provided by LINCO Research, Inc. (St. Louis, MO). Human Pituitary LINCOplex Kit
      is utilized for simultaneous quantification of six pituitary hormones in serum,
      plasma, tissue lysate, and culture supernatant samples: Prolactin, FSH, LH, TSH,
      GH, and ACTH.

PMID- 19381952
TI  - High-throughput analysis of serum antigens using sandwich ELISAs on microarrays.
AB  - Enzyme-linked immunosorbent assay (ELISA) microarrays promise to be a powerful
      tool for the detection and validation of disease biomarkers. ELISA microarrays
      are capable of simultaneous detection of many proteins using a small sample
      volume. Although there are many potential pitfalls to the use of ELISA
      microarrays, these can be avoided by careful planning of experiments. In this
      chapter we describe a high-throughput protocol for processing ELISA microarrays
      that will result in reliable and reproducible data.

PMID- 19381953
TI  - Tissue microarrays as a tool in the discovery and validation of tumor markers.
AB  - Tissue microarrays are a platform of condensed histopathology that has
      revolutionized the translation of basic science to clinical utility. Tissue
      microarrays have resulted in a paradigm shift from histopathology to
      immunopathology and moved analysis of small selected samples sets of tens of
      specimens to a high-throughput environment of hundreds of specimens. Tissue
      microarrays have influenced validation strategies, but have a role in discovery
      as well, allowing a pathways approach to analysis of tumors.

PMID- 19381954
TI  - Quantitative, fluorescence-based in-situ assessment of protein expression.
AB  - As companion diagnostics grow in prevalence and importance, the need for accurate
      assessment of in situ protein concentrations has increased. Traditional
      immunohistochemistry (IHC), while valuable for assessment of context of
      expression, is less valuable for quantification. The lack of rigorous
      quantitative potential of traditional IHC led to our development of an
      immunofluorescence-based method now commercialized as the AQUA technology.
      Immunostaining of tissue samples, image acquisition, and use of AQUA software
      allow investigators to quickly, efficiently, and accurately measure levels of
      expression within user-defined subcellular or architectural compartments. IHC
      analyzed by AQUA shows high reproducibility and demonstrates protein measurement
      accuracy similar to ELISA assays. The process is largely automated, eliminating
      potential error, and the resultant scores are exported on a continuous scale.
      There are now numerous published examples where observations made with this
      technology are not seen by traditional methods.

PMID- 19381955
TI  - Tumor marker discovery by expression profiling RNA from formalin fixed paraffin
      embedded tissues.
AB  - Clear identification among early-stage cancer patients of those at highest risk
      of having metastatic disease would be of great benefit in treatment planning and
      management. Considerable additional benefit would accrue to high-risk patients if
      their responses to specific therapeutic alternatives could be predicted.
      Molecular biomarkers in the form of gene expression profiles are proving to be
      more effective tools for both prognostic and predictive patient stratification
      than more traditional methods such as patient demographics and histopathology
      indicators. Such biomarkers must be clinically validated before they can be
      effectively used to manage patients in clinical studies or clinical practice.
      This can be most efficiently accomplished by analyzing archived clinical samples
      with well-characterized clinical outcomes. Doing studies of this type requires
      reoptimization of traditional molecular expression profiling techniques to
      analyze RNA from fixed paraffin-embedded tissues. We have modified molecular
      methods for RNA extraction, RNA quantification, reverse transcription, and
      quantitative PCR to work optimally in archived clinical samples in order to
      develop a clinically validated assay for breast cancer prognosis and prediction
      of patient response to hormonal and chemotherapy.

PMID- 19381956
TI  - High-throughput mutation screening using a single amplification condition.
AB  - Numerous innovative and high-throughput techniques have been established to
      identify human disease genes. However, DNA sequencing of candidate genes still
      remains as a major limitation in the identification of causative mutations. Much
      of this limitation is due to the time and labor needed for the polymerase chain
      reaction (PCR) optimization and reaction setup. Toward this end, we have
      established a simplified protocol that utilizes a single PCR amplification
      condition. PCR purification is accomplished via enzymatic digestion and all
      products can be sequenced using universal primers. This combination of a single
      amplification condition, single-step purification, and sequencing setup using
      universal primers all contribute to a simple and high-throughput mutation screen.

PMID- 19381957
TI  - DNA sequencing of cancer-related genes for biomarker discovery.
AB  - Dideoxy DNA sequencing is routinely used in research and, increasingly, in
      clinical care for the detection of DNA sequence variants, single nucleotide
      changes, or small insertions or deletions, when the spectrum of DNA variation is
      unknown. DNA sequence variation can be present in tumor tissue that is not
      present in the normal tissue from the same individual. This somatic DNA sequence
      variation is often the cause of abnormal cell growth and/or regulation and,
      ultimately, tumorigenesis. Identification of these oncogenic DNA sequence
      variants has successfully led to the development of cancer therapies, since the
      abnormal protein products created from genomic DNA containing mutations can serve
      as targets for pharmacologic inhibition. Somatic DNA sequence analysis will
      continue to be a valuable technique for biomarker discovery until the complete
      spectrum of DNA variation observed in tumor tissue is understood.

PMID- 19381958
TI  - Analysis of loss of heterozygosity in circulating DNA.
AB  - Analysis of genetic altera tion in circulating DNA can have clinical utility in
      predicting disease outcome. Loss of heterozygosity (LOH) of DNA microsatellites
      has been shown to occur commonly among all chromosomes in various cancers, such
      as melanoma, breast cancer, and lung cancer. In this protocol, we focused on the
      utility of LOH of microsatellite biomarkers for detection of analyzing
      circulating DNA. The protocol describes how PCR is performed on each patient's
      paired DNA samples (normal lymphocyte DNA and serum DNA) using specific
      microsatellite biomarkers followed by post-PCR product analysis using capillary
      array electrophoresis (CAE). The utility of CAE is due to its digitalization and
      accuracy of the post-PCR product results.

PMID- 19381959
TI  - Pharmacogenomics.
AB  - Pharmacogenomics encompasses several major areas including the identification and
      analysis of variations of DNA and RNA that affect the efficacy and toxicity of
      drug therapy. It represents an integration of analytical approaches including DNA
      and RNA detection and quantitation which may be applied to either candidate genes
      or a global genome analysis.

PMID- 19381960
TI  - Study designs in genetic epidemiology.
AB  - Identification of germline mutations that may modulate individual risk of
      developing cancer is a rapidly developing field. Over the last few decades,
      germline mutations in p53, BRCA1, BRCA2, APC, MLH1, MSH2, and MSH6 have been
      identified in families with a large number of relatives who have been diagnosed
      with particular types of cancer. These mutations are rare but substantially
      increase the risk of cancer in carriers, and account for a small fraction of
      cancer cases diagnosed in the general population. The search for common mutations
      that correlate with a very modest increased risk of developing cancer is ongoing.
      With the completion of the Human Genome Project, a large array of methods to
      identify these genes and their variants are under development. The following
      chapter describes methods to provide evidence of a genetic component associated
      with disease risk, how to identify chromosomal regions of interest to identify
      rare but highly penetrant genetic variants, and methods used to identify more
      common mutations which modulate cancer development.

PMID- 19381961
TI  - Developing classifiers for the detection of cancer using multi-analytes.
AB  - The development of a successful classifier from multiple predictors (analytes) is
      a multistage process complicated typically by the paucity of the data samples
      when compared to the number of available predictors. Choosing an adequate
      validation strategy is key for drawing sound conclusions about the usefulness of
      the classifier. Other important decisions have to be made regarding the type of
      prediction model to be used and training algorithm, as well as the way in which
      the markers are selected. This chapter describes the principles of the classifier
      development and underlines the most common pitfalls. A simulated dataset is used
      to illustrate the main concepts involved in supervised classification.

PMID- 19381962
TI  - Metabolomics of cancer.
AB  - Metabolomics, one of the "omic" sciences in systems biology, is the global
      assessment and validation of endogenous small-molecule biochemicals (metabolites)
      within a biologic system. Initially, putative quantitative metabolic biomarkers
      for cancer detection and/or assessment of efficacy of anticancer treatment are
      usually discovered in a preclinical setting (using animal and human cell
      cultures), followed by translational validation of these biomarkers in biofluid
      or tumor tissue. Based on the tumor origin, various biofluids, such as blood,
      urine, and expressed prostatic secretions, can be used for validating metabolic
      biomarkers noninvasively in cancer patients. Metabolite detection and
      quantification is usually carried out by nuclear magnetic resonance (NMR)
      spectroscopy, while mass spectrometry (MS) provides another highly sensitive
      metabolomics technology. Usually, sophisticated statistical analyses are carried
      out either on spectroscopic or on quantitative metabolic data sets to provide
      meaningful information about the metabolic makeup of the sample. Various
      metabolic biomarkers, related to glycolysis, mitochondrial citric cycle acid,
      choline and fatty acid metabolism, were recently reported to play important roles
      in cancer development and responsiveness to anticancer treatment using NMR-based
      metabolic profiling.Carefully designed and validated protocols for sample
      handling and sample extraction followed by appropriate NMR techniques and
      statistical analyses, which are required to establish quantitative (1)H-NMR-based
      metabolomics as a reliable analytical tool in the area of cancer biomarker
      discovery, are discussed in the present chapter.

PMID- 19381963
TI  - MRI and MRS of human brain tumors.
AB  - The purpose of this chapter is to provide an introduction to magnetic resonance
      imaging (MRI) and magnetic resonance spectroscopy (MRS) of human brain tumors,
      including the primary applications and basic terminology involved. Readers who
      wish to know more about this broad subject should seek out the referenced books
      (1. Tofts (2003) Quantitative MRI of the brain. Measuring changes caused by
      disease. Wiley; Bradley and Stark (1999) 2. Magnetic resonance imaging, 3rd
      Edition. Mosby Inc; Brown and Semelka (2003) 3. MRI basic principles and
      applications, 3rd Edition. Wiley-Liss) or reviews (4. Top Magn Reson Imaging
      17:127-36, 2006; 5. JMRI 24:709-724, 2006; 6. Am J Neuroradiol 27:1404-1411,
      2006).MRI is the most popular means of diagnosing human brain tumors. The
      inherent difference in the magnetic resonance (MR) properties of water between
      normal tissues and tumors results in contrast differences on the image that
      provide the basis for distinguishing tumors from normal tissues. In contrast to
      MRI, which provides spatial maps or images using water signals of the tissues,
      proton MRS detects signals of tissue metabolites. MRS can complement MRI because
      the observed MRS peaks can be linked to inherent differences in biochemical
      profiles between normal tissues and tumors.The goal of MRI and MRS is to
      characterize brain tumors, including tumor core, edge, edema, volume, types, and
      grade. The commonly used brain tumor MRI protocol includes T2-weighted images and
      T1-weighted images taken both before and after the injection of a contrast agent
      (typically gadolinium: Gd). The commonly used MRS technique is either point
      resolved spectroscopy (PRESS) or stimulated echo acquisition mode (STEAM).

PMID- 19381964
TI  - Magnetic resonance spectroscopy of living tissues.
AB  - The comprehensive work of both clinical and basic science colleagues has
      demonstrated a clear proof of concept for "in vitro discovered- in vivo
      validated" biomarkers in translational metabolic profiling research using
      magnetic resonance techniques. Major tissue metabolites (initially discovered by
      high-resolution in vitro techniques on cancer specimens) can be translated into
      in vivo protocols based on noninvasive magnetic resonance spectroscopy (MRS).
      Using (1)H- and (31)P-MRS on living animals or patients, a decrease in citrate
      and polyamines in prostate cancer, an increase of cholines in breast cancer, as
      well as a decreased NAA and an increased lactate in gliomas during cancer
      progression can be assessed noninvasively. MRS can be used to follow up
      conventional cytotoxic as well as targeted anticancer therapies, which has been
      extensively done in animal models of cancer. This review focuses on applications
      and protocol development for in vivo (1)H- and (31)P-MRS on small animal models
      as well as on larger animals in cancer research, diagnosis, and treatment.

PMID- 19381965
TI  - Gene expression analysis using agilent DNA microarrays.
AB  - Hybridization of labeled cDNA to microarrays is an intuitively simple and a
      vastly underestimated process. If it is not performed, optimized, and
      standardized with the same attention to detail as e.g., RNA amplification,
      information may be overlooked or even lost. Careful balancing of the amount of
      labeled cDNA added to each slide reduces dye-bias and slide to slide variation.
      Efficient mixing of the hybridization solution throughout the hybridization
      reaction increases signals several fold. The amount of near perfect target-probe
      hybrids may be reduced by efficient stringency washes of the hybridized
      microarray slides.

PMID- 19381966
TI  - RNA preparation and characterization for gene expression studies.
AB  - Much information can be obtained from knowledge of the relative expression level
      of each gene in the transcriptome. With the current advances in technology as
      little as a single cell is required as starting material for gene expression
      experiments. The mRNA from a single cell may be linearly amplified to an excess
      of 10(6)-fold. Reverse transcription and fluorescent labeling of the amplified
      RNA yields a stable target for subsequent hybridization to DNA microarrays.

PMID- 19381967
TI  - Fabrication using contact spotter.
AB  - Many steps of optimization are needed to achieve large-scale fabrication of high
      quality DNA microarrays. These steps involve the printing instrument, the probes
      to be printed, microarray slides, and spotting buffer together with the
      surrounding environment, such as humidity and temperature. Robust microarray
      production requires not only appropriate reagents, equipment, and established
      procedures, but also devoted and experienced personnel. It is a challenging and
      craftsman like activity, but at the same time highly rewarding in terms of
      flexibility and cost efficiency. Outlined here is the workflow of a high
      throughput microarray production line.

PMID- 19381968
TI  - Immobilization chemistries.
AB  - Among the parameters which influence the success of a microarray experiment, the
      attachment of the nucleic acid captures to the support surface plays a decisive
      role.This article attempts to review the main concepts and ideas of the multiple
      variants which exist in terms of the immobilization chemistries used in nucleic
      acid microarray technology. Starting from the attachment of unmodified nucleic
      acids to modified glass slides by adsorption, further strategies for the coupling
      of nucleic acid capture molecules to a variety of support materials are surveyed
      with a focus on the reactive groups involved in the respective process.After a
      brief introduction, an overview is given about microarray substrates with special
      emphasis on the approaches used for the activation of these - usually chemically
      inert - materials. In the next sections strategies for the "undefined" and
      "defined" immobilization of captures on the substrates are described. While the
      latter approach tries to accomplish the coupling via a defined reactive moiety of
      the molecule to be immobilized, the former mentioned techniques involve multiply
      occurring reactive groups in the capture.The article finishes with an example for
      microarray manufacture, the production of aminopropyltriethoxysilane (APTES)
      functionalized glass substrates to which PDITC homobifunctional linker molecules
      are coupled; on their part providing reactive functional groups for the covalent
      immobilization of pre-synthesized, amino-modified oligonucleotides.This survey
      does not seek to be comprehensive rather it tries to present and provide key
      examples for the basic techniques, and to enable orientation if more detailed
      studies are needed. This review should not be considered as a guide to how to use
      the different chemistries described, but instead as a presentation of various
      principles and approaches applied in the still evolving field of nucleic acid
      microarray technology.

PMID- 19381969
TI  - Fabrication of DNA microarray.
AB  - There are many ways to fabricate DNA microarrays. The four main types of arrays
      are spotted arrays of pre-made DNA probes, in situ synthesis of DNA arrays,
      random bead arrays and suspension arrays. The different types of array can
      address different biological assays. Spotted arrays are suitable for application
      using small to medium number of probes, e.g. focused genotyping, bacterial
      diagnostics and gene expression analysis. In situ synthesized arrays and random
      bead arrays are suitable for applications where medium to large number of probes
      are needed such as genome wide screens for single nucleotide polymorphisms.
      Suspension arrays are suitable for applications requiring small number of probes.
      The chapter will include details of fabrication methods and a comparison of the
      strengths, weaknesses and future use of each method.

PMID- 19381970
TI  - Design of tag SNP whole genome genotyping arrays.
AB  - Whole genome association studies have recently been enabled by combining tag SNP
      information derived from the International HapMap project with novel whole genome
      genotyping array technologies. In particular, Infinium whole genome genotyping
      (WGG) technology now has the power to genotype over 1 million SNPs on a single
      array. Additionally, this assay provides access to virtually any SNP in the
      genome enabling selection of optimized SNP content . In this chapter, we provide
      an overview of the tag SNP-based selection strategy for Infinium whole-genome
      genotyping BeadChips, including the Human 1 M BeadChip. These advances in both
      SNP content and technology have enabled both large-scale whole-genome disease
      association (WGAS) and copy number variation (CNV) studies with the ultimate goal
      of identifying common genetic variants, disease-associated loci, proteins, and
      biomarkers.

PMID- 19381971
TI  - Comparative genomic hybridization: microarray design and data interpretation.
AB  - Microarray-based Comparative Genomic Hybridization (array-CGH) has been applied
      for a decade to screen for submicroscopic DNA gains and losses in tumor and
      constitutional DNA samples. This method has become increasingly flexible with the
      integration of new biological resources generated by genome sequencing projects.
      In this chapter, we describe alternative strategies for whole genome screening
      and high resolution breakpoint mapping of copy number changes by array-CGH, as
      well as tools available for accurate analysis of array-CGH experiments. Although
      most methods listed here have been designed for microarrays comprising large
      insert clones, they can be adapted easily to other types of microarray platforms,
      such as those constructed from printed or synthesized oligonucleotides.

PMID- 19381972
TI  - Probe design for expression arrays using OligoWiz.
AB  - Since all measurements from a DNA microarray is dependant on the probes used, a
      good choice of probes is of vital importance when designing custom microarrays.
      This chapter describes how to design expression arrays using the OligoWiz
      software suite. The desired general features of good probes and the issues which
      probe design must address are introduced and a conceptual (rather than
      mathematical) description of how OligoWiz scores the quality of the potential
      probes is presented. This is followed by a detailed step-by-step guide to
      designing expression arrays with OligoWiz.The scope of this chapter is
      exclusively on expression arrays. For an in-depth review of the entire field of
      probe design (including a comparison of different probe design packages) as well
      as instructions on how to produce special purpose arrays (e.g., splice detection
      arrays), please refer to (1).

PMID- 19381973
TI  - Chromatin immunoprecipitation using microarrays.
AB  - Chromatin immunoprecipitation (ChIP) is a powerful procedure to investigate the
      interactions between proteins and DNA. ChIP-chip combines chromatin
      immunoprecipitation and DNA microarray analysis to identify protein-DNA
      interactions that occur in vivo. This genome-wide analysis of protein-DNA
      association is carried out in several steps including chemical cross-linking,
      cell lysis, DNA fragmentation and immunoaffinity purification that allow the
      identification of DNA interactions and provide a powerful tool for genome-wide
      investigations. Immunoprecipitated DNA fragments associated with the desired
      protein are amplified, labelled and hybridized to DNA microarrays to detect
      enriched signals compared to a labelled reference sample.

PMID- 19381974
TI  - Comparative genomic hybridization: DNA labeling, hybridization and detection.
AB  - Array-CGH involves the comparison of a test to a reference genome using a
      microarray composed of target sequences with known chromosomal coordinates. The
      test and reference DNA samples are used as templates to generate two probe DNAs
      labeled with distinct fluorescent dyes. The two probe DNAs are co-hybridized on a
      microarray in the presence of Cot-1 DNA to suppress unspecific hybridization of
      repeat sequences. After slide washes and drying, microarray images are acquired
      on a laser scanner and fluorescent intensities from every target sequence spot on
      the array are extracted using dedicated computer programs. Intensity ratios are
      calculated and normalized to enable data interpretation. Although the protocols
      explained in this chapter correspond primarily to the use of large-insert clone
      microarrays in either manual or automated fashion, necessary adaptations for
      hybridization on microarrays comprising shorter target DNA sequences are also
      briefly described.

PMID- 19381975
TI  - Comparative genomic hybridization: DNA preparation for microarray fabrication.
AB  - The spatial resolution of microarray-based comparative genomic hybridization
      (array-CGH) is dependent on the length and density of target DNA sequences
      covering the chromosomal region of interest. Here we describe the methods
      developed at the Wellcome Trust Sanger Institute (Cambridge, UK) to construct
      microarrays comprising large-insert clones available through genome sequencing
      projects. These methods are applicable to Bacterial and Phage Artificial
      Chromosomes (BAC and PAC) as well as fosmid and cosmid clones. The protocols are
      scalable for the construction of microarrays composed of several hundreds up to
      several ten thousands clones.

PMID- 19381976
TI  - Resequencing arrays for diagnostics of respiratory pathogens.
AB  - Microarray technology has revolutionized the detection and analysis of microbial
      pathogens. The success of this technology is evident from the various microarrays
      that have been developed for this purpose, variation in the density of probes,
      and the time ranges required for assay completion. Among these, high-density re
      sequencing microarrays have demonstrated great potential for detecting bacterial,
      viral pathogens, and virulence markers. Resequencing microarrays use closely
      overlapping probe sets to determine a target organism's nucleotide sequence.
      Hybridization to a series of perfect matched probes provides confirmatory
      presence/absence information, while hybridization to mismatched probes reveals
      strain-specific single nucleotide polymorphism (SNP) data. This approach provides
      sequence information of the diagnostic regions of detected organisms that is
      considerably more informative over that provided from other microarray
      techniques.

PMID- 19381977
TI  - Genotyping single nucleotide polymorphisms by multiplex minisequencing using tag
      arrays.
AB  - The need for multiplexed methods for SNP genotyping has rapidly increased during
      the last decade. We present here a flexible system that combines highly specific
      genotyping by minisequencing single-base extension with the advantages of a
      microarray format that allows highly multiplexed and parallel analysis of any
      custom selected SNPs.Cyclic minisequencing reactions with fluorescently labeled
      dideoxynucleotides (ddNTPs) are performed in solution using multiplex PCR product
      as template and detection primers, designed to anneal immediately adjacent and
      upstream of the SNP site. The detection primers carry unique Tag-sequences at
      their 5' ends and oligonucleotides complementary to the Tag-sequence, cTags, are
      immobilized on a microarray. After extension, the tagged detection primers are
      allowed to hybridize to the cTags, and the fluorescent signals from the array are
      measured and the genotypes are deduced by cluster analysis of the incorporated
      labels. The "array of arrays" format of the system, accomplished by a silicon
      rubber grid to form separate reaction chambers, allows either 80 or 16 samples to
      be analyzed for up to 200 or 600 SNPs, respectively on a single microscope slide.

PMID- 19381978
TI  - Whole-genome genotyping on bead arrays.
AB  - In this review, we describe the laboratory implementation of Infinium whole
      genome genotyping (WGG) technology for whole genome association studies and copy
      number studies. Briefly, the Infinium WGG assay employs a single tube whole
      genome amplification reaction to amplify the entire genome; genomic loci of
      interest are captured on an array by specific hybridization of picomolar
      concentrations amplified gDNA. After target capture, single nucleotide
      polymorphisms (SNPs) are genotyped on the array by a primer extension reaction
      using hapten-labeled nucleotides. The resultant hapten signal is amplified by
      immunhistochemical sandwich staining and the array is read out on a high
      resolution confocal scanner. We have combined this Infinium assay with high
      density BeadChips to create the first array platform capable of genotyping over 1
      million SNPs per slide. Additionally, the complete Infinium assay is automated
      using Tecan GenePaint slide processing system. Hybridization, washing, array
      based primer extension and staining are performed directly in the Tecan capillary
      gap Te-Flow Through chambers. This automation process greatly increases assay
      robustness and throughput while enabling Laboratory Information Management System
      (LIMS) control of sample tracking. Finally, we give several examples of how this
      advance in genotyping technology is being applied in whole genome association and
      copy number studies.

PMID- 19381979
TI  - Microarray temperature optimization using hybridization kinetics.
AB  - In any microarray hybridization experiment, there are contributions at each probe
      spot due to the match and numerous mismatch target species (i.e., cross
      hybridizations). One goal of temperature optimization is to minimize the
      contribution of mismatch species; however, achieving this goal may come at the
      expense of obtaining equilibrium reaction conditions. We employ two-component
      thermodynamic and kinetic models to study the trade-offs involved in temperature
      optimization. These models show that the maximum selectivity is achieved at
      equilibrium, but that the mismatch species controls the time to equilibrium via
      the competitive displacement mechanism. Also, selectivity is improved at lower
      temperatures. However, the time to equilibrium is also extended, so that greater
      selectivity cannot be achieved in practice. We also employ a two-color real-time
      microarray reader to experimentally demonstrate these effects by independently
      monitoring the match and mismatch species during multiplex hybridization. The
      only universal criterion that can be employed is to optimize temperature based
      upon attaining equilibrium reaction conditions. This temperature varies from one
      probe to another, but can be determined empirically using standard microarray
      experimentation methods.

PMID- 19381980
TI  - Genotyping of mutations in the beta-globin gene using allele specific
      hybridization.
AB  - The use of DNA microarrays for genotyping is economically favorable when compared
      to real-time PCR and DNA sequencing. Here, we demonstrate a DNA microarray-based
      assay using allele-specific oligonucleotide (ASO) probes for genotyping mutations
      in the beta-globin gene. The assay makes use of agarose film coated glass slides
      as substrate, unmodified melting temperature matched ASO probes, target
      amplification and labeling using T7 in vitro transcription, mixing during
      hybridization and finally visualization using a fluorescent scanner. In this
      chapter we will emphasize on probe design, optimization, and validation of an
      allele-specific hybridization assay.

PMID- 19381981
TI  - Target preparation for genotyping specific genes or gene segments.
AB  - Generation of single stranded target is of high importance for hybridization
      reactions on oligonucleotide microarrays. Several methods have been established
      for production of single stranded DNA and in vitro transcribed RNA. Here we
      describe three robust methods for target amplification from purified genomic DNA
      or pre-amplified DNA. The protocols include incorporation of biotin labels in the
      target molecules and allow for biotin/streptavidin chemistry to be utilized for
      flexibility in choice of visualization strategy.

PMID- 19381982
TI  - Introduction to microarray technology.
AB  - DNA microarrays can be used for large number of application where high-throughput
      is needed. The ability to probe a sample for hundred to million different
      molecules at once has made DNA microarray one of the fastest growing techniques
      since its introduction about 15 years ago. Microarray technology can be used for
      large scale genotyping, gene expression profiling, comparative genomic
      hybridization and resequencing among other applications. Microarray technology is
      a complex mixture of numerous technology and research fields such as mechanics,
      microfabrication, chemistry, DNA behaviour, microfluidics, enzymology, optics and
      bioinformatics. This chapter will give an introduction to each five basic steps
      in microarray technology that includes fabrication, target preparation,
      hybridization, detection and data analysis. Basic concepts and nomenclature used
      in the field of microarray technology and their relationships will also be
      explained.

PMID- 19381983
TI  - Culture and epidemiology special issue: towards an integrated study of culture
      and population health.

PMID- 19381984
TI  - Culture as an explanation in population health.
AB  - In the last two decades, culture has emerged in population health as a common
      explanation for health outcomes and disparities. This paper systematically
      reviews such cultural accounts, focusing on a historical sample of articles from
      prominent population health journals (1930-2008, n=100) and a contemporary sample
      of articles in the American Journal of Public Health (2008, n=95). The review
      reveals that references to culture rarely (1) specify the precise pathways by
      which culture influences health or (2) assess the plausibility of these pathways.
      Despite these weaknesses, a few studies have begun to clarify, measure, and
      assess how culture can influence health outcomes, and these articles reflect
      promising new avenues for understanding how cultural factors influence variation
      in health and well-being.

PMID- 19381985
TI  - Culture in psychiatric epidemiology: using ethnography and multiple mediator
      models to assess the relationship of caste with depression and anxiety in Nepal.
AB  - BACKGROUND: The causes of ethnic and caste-based disparities in mental health are
      poorly understood. AIM: The study aimed to identify mediators underlying caste
      based disparities in mental health in Nepal. SUBJECTS AND METHODS: A mixed
      methods ethnographic and epidemiological study of 307 adults (Dalit/Nepali, n=75;
      high caste Brahman and Chhetri, n=232) was assessed with Nepali versions of Beck
      Depression (BDI) and Anxiety (BAI) Inventories. RESULTS: One-third (33.7%) of
      participants were classified as depressed: Dalit/Nepali 50.0%, high caste 28.4%.
      One quarter (27.7%) of participants were classified as anxious: Dalit/Nepali
      50.7%, high caste 20.3%. Ethnographic research identified four potential
      mediators: Stressful life events, owning few livestock, no household income, and
      lack of social support. The direct effect of caste was 1.08 (95% CI -1.10-3.27)
      on depression score and 4.76 (95% CI 2.33-7.19) on anxiety score. All four
      variables had significant indirect (mediation) effects on anxiety, and all but
      social support had significant indirect effects on depression. CONCLUSION: Caste
      based disparities in mental health in rural Nepal are statistically mediated by
      poverty, lack of social support, and stressful life events. Interventions should
      target these areas to alleviate the excess mental health burden born by
      Dalit/Nepali women and men.

PMID- 19381986
TI  - Tracking biocultural pathways in population health: the value of biomarkers.
AB  - BACKGROUND: Cultural factors and biomarkers are emerging emphases in social
      epidemiology that readily ally with human biology and anthropology. Persistent
      health challenges and disparities have established biocultural roots, and
      environment plays an integral role in physical development and function that form
      the bases of population health. Biomarkers have proven to be valuable tools for
      investigating biocultural bases of health disparities. AIMS: We apply recent
      insights from biology to consider how culture gets under the skin and evaluate
      the construct of embodiment. We analyse contrasting biomarker models and
      applications, and propose an integrated model for biomarkers. Three examples from
      the Great Smoky Mountains Study (GSMS) illustrate these points. SUBJECTS AND
      METHODS: The longitudinal developmental epidemiological GSMS comprises a
      population-based sample of 1420 children with repeated measures including mental
      and physical health, life events, household conditions, and biomarkers for
      pubertal development and allostatic load. RESULTS: Analyses using biomarkers
      resolved competing explanations for links between puberty and depression,
      identified gender differences in stress at puberty, and revealed interactive
      effects of birthweight and postnatal adversity on risk for depression at puberty
      in girls. CONCLUSION: An integrated biomarker model can both enrich epidemiology
      and illuminate biocultural pathways in population health.

PMID- 19381987
TI  - Blood lead levels and growth status among African-American and Hispanic children
      in Dallas, Texas--1980 and 2002: Dallas Lead Project II.
AB  - OBJECTIVE: The purpose of this investigation is to analyze childhood blood lead
      levels and growth status (ages 2-12) in Dallas, Texas lead smelter communities in
      the 1980s and 2002, where smelters operated from 1936 to 1990. METHODS AND
      MATERIALS: A sample of convenience study design was used in two cohorts (n=360):
      1980-1989 (n=191) and 2002 (n=169). Multivariate analysis of variance and
      covariance and tandem multiple regressions were used to evaluate the association
      between stature and blood lead level in two time periods. RESULTS: In 2002
      average child blood lead level (1.6 microg/dL+/-0.2 SE) was significantly
      (p<0.001) lower compared to the 1980 cohort mean level (23.6 microg/dL+/-1.3 SE).
      Average height and weight in 2002 were 4.5 cm and 4.0 kg greater, respectively,
      than in 1980. Lowered blood lead level was associated with 3.9 cm, 3.5 kg and 1.1
      units greater height, weight and body mass index (BMI), respectively. Cohort
      effect was associated with greater height (0.6 cm), weight (0.5 kg) and BMI
      (0.1). CONCLUSION: This investigation reports on child growth in a community
      before and after the transition from high to low blood lead levels over several
      decades. Using child growth as a proxy, health status of Dallas's lead smelter
      communities increased markedly over the past two decades, primarily because of
      lower blood lead levels, while the poverty rate was only marginally lower.

PMID- 19381988
TI  - Admixture estimates for the population of Havana City.
AB  - BACKGROUND: The Cuban population is essentially a result of the admixture between
      Spanish, West African and, to a lesser degree, Amerindian tribes that inhabited
      the island. AIM: The study analysed the genetic structure of the three principal
      ethnic groups from Havana City, and the contribution of parental populations to
      its genetic pool. SUBJECTS AND METHODS: According to genealogical information and
      anthropological traits, 206 subjects were classified as Mulatto, of Spanish
      decent or of African descent. Seventeen Ancestry Informative Markers, with high
      difference in frequency between parental populations, were selected to estimate
      individual and group admixture proportions. The statistical analyses were
      performed using the ADMIX, ADMIX95 and STRUCTURE 2.1 packages. RESULTS: The
      results demonstrate a high level of European and African admixture in Mulattos
      (57-59% European; 41-43% West African). The European contribution was higher in
      those of Spanish descent (85%) while in those of African descent, the West
      African contribution ranged between 74% and 76%. Genetic structure was only
      detected in Mulattos and those of African descent. An Amerindian contribution was
      not detectable in the studied sample. CONCLUSION: Our findings indicate the
      existence of admixture and genetic structure in the population of Havana City.
      This study represents one of the first steps towards understanding Cuban
      population admixture in order to produce successful experimental designs for
      admixture mapping.

PMID- 19381989
TI  - Patterns of emotion regulation and psychopathology.
AB  - Emotion regulatory strategies such as higher expressive suppression and lower
      cognitive reappraisal may be associated with increased psychopathology (Gross &
      John, 2003). Yet, it is unclear whether these strategies represent distinct
      cognitive styles associated with psychopathology, such that there are individuals
      who are predominantly "suppressors" or "reappraisers." Using cluster analysis, we
      examined whether women with and without exposure to potentially traumatic events
      evidence distinct patterns of emotion regulation frequency, capacity,
      suppression, and cognitive reappraisal. Four patterns emerged: high regulators;
      high reappraisers/low suppressors; moderate reappraisers/low suppressors; and low
      regulators. Individuals who reported infrequently and ineffectively regulating
      their emotions (low regulators) also reported higher depression, anxiety, and
      posttraumatic stress disorder (PTSD). In contrast, individuals who reported
      frequently and effectively using reappraisal and low levels of suppression (high
      reappraisers/low suppressors) reported the lowest levels of these symptoms,
      suggesting that this specific combination of emotion regulation may be most
      adaptive. Our findings highlight that the capacity to regulate emotions and the
      ability to flexibly apply different strategies based on the context and timing
      may be associated with reduced psychopathology and more adaptive functioning.

PMID- 19381990
TI  - Differences in human phospholipid transfer protein activity following incubation
      of Fungizone compared to lipid-based Amphotericin-B formulations in
      normolipidemic and hyperlipidemic plasma.
AB  - AIM: To investigate how different formulations of Amphotericin-B (Amp-B) affect
      the activity of phospholipid transfer protein (PLTP) when incubated with
      hyperlipidemic and normolipidemic plasma at physiological temperature (37 degrees
      C). METHODS: Six hyperlipidemic and six normolipidemic plasma samples were
      collected and tested for protein concentration. Equivalent protein levels (25
      microg) were then tested for PLTP activity using an in vitro established kit at
      physiological temperature (37 degrees C). Increasing concentrations of different
      Amp-B formulations (1, 2, and 5 microg/mL) in the pharmacological range were then
      added to the plasma and tested for activity from 5 to 90 minutes. The Amp-B
      formulations used in the study were Fungizone, Abelcet, and AmBisome. RESULTS: In
      normolipidemic plasma, PLTP activity was found to be increased by Abelcet and
      AmBisome but inhibited by Fungizone. In hyperlipidemic plasma, PLTP activity was
      found to be increased by Abelcet and AmBisome but not changed by Fungizone. The
      Vm value for Abelcet and AmBisome was higher than Fungizone(; although, no
      difference was observed in the Km values between formulations. CONCLUSIONS:
      Findings suggest that lipid-based formulations of Amp-B promote the transfer of
      Amp-B into high-density lipoprotein fractions at a degree of increase inversely
      proportional to the lipid levels in the plasma.

PMID- 19381991
TI  - Small, qualitative changes in fatty acid intake decrease plasma low-density
      lipoprotein-cholesterol levels in mildly hypercholesterolemic outpatients on
      their usual high-fat diets.
AB  - OBJECTIVE: The diet is the first step in managing hypercholesterolemia. The
      objective of the present study is to assess whether moderate changes in dietary
      fatty acids improve plasma lipid parameters in mildly hypercholesterolemic
      outpatients. METHODS: Using a randomized double-blind study, 121 outpatients
      within two groups received an isocaloric amount of unsaturated margarine or
      butter. Clinical and anthropometric measurements and a 3-day food record were
      made. Chi-square and Fisher's tests were used to compare qualitative variables
      and the general linear procedure was used to compare the groups. Additional
      analyses were performed after adjustment. RESULTS: There was a significant
      difference (P <0.03) in low-density lipoprotein-cholesterol levels between the
      groups. Total cholesterol, low-density lipoprotein-cholesterol, non-high-density
      lipoprotein-cholesterol and apolipoprotein B values decreased in the unsaturated
      group in comparison with the saturated group. Low-density lipoprotein-cholesterol
      changes were correlated with the variation in polyunsaturated fatty acid intake
      and with plasma phospholipid linoleic acid levels. CONCLUSION: A small change in
      saturated by polyunsaturated fatty acid intake may improve plasma lipid
      parameters in mildly hypercholesterolemic subjects.

PMID- 19381992
TI  - Radical scavenging activity of orange and tangerine varieties cultivated in
      Brazil.
AB  - Four citrus fruit varieties cultivated in Brazil (two kinds of sweet orange and
      two kinds of tangerine) were analyzed for physicochemical characteristics
      contents of total phenolics, total carotenoids and ascorbic acid, and antioxidant
      activities. The antioxidant activities of aqueous, methanolic, and acetone
      extracts of the citrus fruit juices were assessed on the basis of their ability
      to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH*). The cravo tangerine has the
      highest content of citric acid, while the pera orange is richest in ascorbic
      acid. The lima orange has the highest total phenolic contents, and the ponkan the
      highest total carotenoids. The antioxidant activities, expressed as the
      concentration of antioxidant able to scavenge 50% of the initial DPPH* (EC50),
      ranged from 139.1 +/- 27.3 to 182.2 +/- 28.8 g extract/l for juice of orange
      varieties and 186.3 +/- 29.6 to 275.5 +/- 3.3g extract/l for juice of tangerine
      citrus varieties. In methanolic extracts the EC50 ranged from 192.5 +/- 43.1 to
      267.4 +/- 41.4 g extract/l for orange varieties and from 225.2 +/- 69.8 to 336.3
      +/- 27.2 g extract/l for tangerine varieties. For EC50 values of acetone
      fractions, there were no statistically significant differences between the
      different varieties. For every citrus fruit in the present study, the radical
      scavenging capacity was higher in the aqueous than in the methanolic or acetone
      fractions.

PMID- 19381993
TI  - Development of a quantitative food frequency questionnaire for assessing food,
      nutrient, and heterocyclic aromatic amines intake in Japanese Brazilians for a
      colorectal adenoma case-control study.
AB  - PRIMARY OBJECTIVE: To develop of a quantitative food frequency questionnaire
      (QFFQ) to assess intake of specific foods, nutrients and heterocyclic aromatic
      amines (HAAs) in a case-control study of colorectal adenoma. METHODS AND
      PROCEDURES: A cross-sectional survey conducted in a hospital in Sao Paulo,
      Brazil. A trained dietitian collected 24-h recalls from 60 Japanese Brazilian
      outpatients (29 men and 31 women; mean age 58 years and 57 years, respectively).
      MAIN OUTCOMES AND RESULTS: Fruit, vegetable and legume intake was high, with mean
      daily servings consumed in men and women of 8.2 and 6.9, respectively. The QFFQ
      contains 161 food items presented in 15 food groupings, with particular emphasis
      paid to the HAA content of meat, fish and chicken items. CONCLUSIONS: We have
      developed a QFFQ appropriate for Japanese Brazilians that will allow us to
      estimate HAA intake and will be used to examine our hypotheses related to foods,
      nutrients and HAAs, and diet-gene interactions in colorectal neoplasia in this
      population.

PMID- 19381994
TI  - Experimental in vitro arterial reactivity and tissue culture solutions alter the
      time-dependent stability of anthocyanins from elderberry, chokeberry, and
      bilberry extracts.
AB  - We examined the effect of solutions commonly used for in vitro assessment of
      blood vessel physiology and pharmacology on the half-lives of monomeric
      anthocyanins contained in extracts from elderberry, chokeberry, and bilberry. We
      observed that monomeric anthocyanin degradation in all extracts was accelerated
      when they were solubilized in an in vitro vascular physiological salt solution
      (PSS) compared with extracts in purified water. Degradation was accelerated
      further by increasing the temperature of the PSS to 37 degrees C and bubbling it
      with 95% oxygen/5% carbon dioxide. A common, complex, tissue culture media
      yielded similar results to the physiological salt solution at 37 degrees C. We
      also observed that the percentage polymeric color estimated by bisulfite
      bleaching corresponded to monomeric degradation in PSS. These results suggest
      that exposure of anthocyanins to physiological conditions that mimic those in the
      human body may stimulate the conversion of monomeric anthocyanins to their
      polymeric forms. Such conversion would probably contribute to the effects of
      anthocyanins on physiological functions in in vitro experiments and needs to be
      considered when evaluating effects of these compounds on physiological processes.

PMID- 19381995
TI  - Childhood executive function inventory (CHEXI): a promising measure for
      identifying young children with ADHD?
AB  - The present study investigated whether the Childhood Executive Function Inventory
      (CHEXI) can discriminate between young children fulfilling the diagnostic
      criteria for attention-deficit/hyperactivity disorder (ADHD) and normally
      developing children. Unlike other executive function rating instruments, the
      CHEXI focuses specifically on inhibitory control and working memory, without
      including items that overlap with the diagnostic criteria of ADHD. The CHEXI was
      found to discriminate very well between children fulfilling the criteria for ADHD
      and normally developing children, also when controlling for the effect of IQ and
      socioeconomic status (SES). Both sensitivity and specificity of the two CHEXI
      subscales were shown to be high using either parent or teacher ratings. The
      highest overall classification rate was found for parent ratings on the
      inhibition subscale, with sensitivity and specificity reaching 93.3. To
      summarize, the CHEXI should be considered a promising measure for identifying
      young children with ADHD, although it is for future research to determine whether
      the CHEXI can be successfully used to also discriminate between different
      psychopathological groups.

PMID- 19381996
TI  - The effect of unilateral amygdala removals on detecting fear from briefly
      presented backward-masked faces.
AB  - Facial expressions convey information about the moods and intentions of other
      people and provide important clues about environmental threats. Previous research
      has shown that patients with unilateral amygdala removals have difficulties
      rating the intensity of fearful facial expressions. The aim of the current study
      was to investigate whether patients with amygdala lesions would also be impaired
      at detecting fear from briefly presented, backward-masked faces. We found that
      patients with either left or right temporal lobe excisions were impaired at
      rating fear intensity in faces, whereas fear detection difficulties were
      predominantly seen in those who had undergone a left temporal lobectomy.
      Intriguingly, patients with amygdala damage found it more difficult to recognize
      fear from faces shown for unlimited durations than to detect fear from briefly
      presented faces. Moreover, there was little overlap between impairments of fear
      detection and fear-rating, indicating that task demands are crucially important
      in determining fear-processing deficits.

PMID- 19381997
TI  - The development of a survey to examine knowledge about and attitudes toward
      concussion in high-school students.
AB  - The development of a new measure of concussion knowledge and attitudes that is
      more comprehensive and psychometrically sound than previous measures is
      described. A group of high-school students (N = 529) completed the measure. The
      measure demonstrated fair to satisfactory test-retest reliability (knowledge
      items, r = .67; attitude items, r = .79). Exploratory factor analysis of the
      attitude items revealed a four-factor solution (eigenvalues ranged from 1.07
      3.35) that displayed adequate internal consistency (Cohen's alpha range = .59
      .72). Cluster analysis of the knowledge items resulted in a three-cluster
      solution distributed according to their level of difficulty. The potential uses
      for the measure are described.

PMID- 19381998
TI  - Women's sexual satisfaction as a predictor of well-being in same-sex versus mixed
      sex relationships.
AB  - Structural equation modelling was used to assess the strengths of the links
      between sexual satisfaction and self-reported (a) relationship well-being, (b)
      mental health, and (c) physical health for women in same-sex (i.e., homosexual, n
      = 114) versus mixed-sex (i.e., heterosexual, n = 208) relationships. Participants
      came from a large-scale Internet study. Sexual satisfaction was found to be an
      extremely strong predictor of relational well-being, a strong predictor of mental
      health, and a weak to moderately strong predictor of physical health. A two-group
      comparison model indicated that the strength of these links was the same,
      regardless of whether the women were in a sexual relationship with a man or with
      another woman.

PMID- 19381999
TI  - Abstracts of the Sixth International Conference on Sport, Leisure and Ergonomics.
      November 14-16, 2007.

PMID- 19382001
TI  - Insulin resistance impairs endothelial function but not adrenergic reactivity or
      vascular structure in fructose-fed rats.
AB  - Obesity and diabetes are major risk factors for the development of vascular
      disease in the lower limbs. Previous studies have demonstrated reduced nitric
      oxide (NO)-mediated vasodilation, increased adrenergic constriction, and inward,
      atrophic remodeling in the limb circulation of obese Zucker rats, but the
      component of the "metabolic syndrome" driving these changes is unclear. Because
      insulin resistance precedes the state of frank diabetes, the current study
      hypothesized that insulin resistance independent of obesity induced by fructose
      feeding would impair microvascular function in the skeletal muscle circulation in
      lean Zucker rats (LZR). A 66% fructose diet impaired glucose tolerance and
      induced moderate insulin resistance with no changes in whole-body hemodynamics of
      anesthetized rats (FF-LZR), compared to control LZR. NO-mediated vasodilation of
      isolated gracilis arteries, assessed in vitro with acetylcholine and sodium
      nitroprusside, was reduced approximately 20% in FF-LZR vs. LZR. NO-independent
      cGMP-mediated vasodilation was unimpaired. Pretreatment of isolated vessels with
      the superoxide scavenger, tempol, improved responses to both vasodilators.
      Reactivity to adrenergic stimulation was unaltered in FF-LZR vs. LZR, although
      constriction to endothelin was increased. Structural and passive mechanical
      characteristics of isolated gracilis arteries were similar in both LZR and FF
      LZR. Taken together, these findings indicate that moderate insulin resistance is
      sufficient to impair endothelial function in an oxidant-dependent manner in the
      rat hindlimb circulation. Other aspects of skeletal muscle vascular function
      documented in obese models, specifically adrenergic tone and inward remodeling,
      must reflect either severe insulin resistance or other aspects of obesity. The
      factors accounting for nonendothelial vasculopathies remain unknown.

PMID- 19382002
TI  - Linezolid-induced complex partial seizures in a patient with epilepsy.

PMID- 19382003
TI  - Is tuberculous lymphadenitis over-diagnosed in Ethiopia? Comparative performance
      of diagnostic tests for mycobacterial lymphadenitis in a high-burden country.
AB  - Ethiopia reports the third highest number of extrapulmonary TB cases globally,
      most of which are lymph node TB (TBLN). We investigated the performance of the
      available diagnostic tests for TBLN. Fine needle aspirate (FNA) and excision
      biopsy samples from affected lymph nodes were collected from 150 consenting
      patients with suspected TBLN visiting regional hospitals in Ethiopia. The
      sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of
      histopathology against culture as reference was 92%, 88%, 97% and 77% and of FNA
      cytology (FNAC) 76%, 88%, 100% and 55%, respectively. Naked eye examination of
      FNA had 67% sensitivity and 64% specificity. HIV coinfection did not diminish the
      performance of macroscopic examination, Ziehl-Neelsen stain, histology or
      cytology examinations. When any positive result in ZN, histopathology or culture
      was considered confirmatory, clinical diagnosis could be confirmed in 85% of the
      patients, suggesting that TBLN is over-diagnosed in up to 15% of cases. With
      combined criteria as reference standard, the sensitivity, specificity, PPV and
      NPV of FNAC was 72%, 100%, 100% and 55%, respectively. FNAC is a practical tool
      that can improve the diagnosis of TBLN in high-burden settings. Over-diagnosis
      alone cannot explain the high burden of LNTB in Ethiopia.

PMID- 19382004
TI  - Prognostic value of histopathological tumour growth patterns at the invasion
      front of T1G3 urothelial carcinoma of the bladder.
AB  - OBJECTIVE: The course of non-muscle-invasive urothelial carcinoma of the bladder
      (BC) staged T1G3 is hardly predictable and treatment is subject of intensive
      debate. In muscle-invasive BC, the infiltrative growth pattern at the tumour
      invasion front was able to predict patients' survival, in contrast to the nodular
      and trabecular growth pattern. The aim of this study was to evaluate this aspect
      in a series of primary T1G3 BC. MATERIAL AND METHODS: The clinical and
      histopathological characteristics of patients with initial T1G3 BC treated
      between 1990 and 2007 at a single institute were retrospectively analysed. After
      independent blinded reassessment by two uropathologists, 205 patients were
      included in the study. The mean follow-up period was 6.7 years (range 0.4-13.2
      years). All patients underwent transurethral resection of the bladder and opted
      for either initial cystectomy (19%) or repeat resection followed by adjuvant
      Bacillus Calmette-Guerin (BCG) instillation therapy (81%). In total, 34% of
      patients were cystectomized. RESULTS: The most common invasion subtype was
      nodular (43.9%), followed by infiltrative (42.0%) and trabecular (14.1%) growth
      patterns. Progression and recurrence-free survival did not differ. However,
      cancer-specific survival rate was statistically significantly worse in
      infiltrative (59.3%) than in nodular (91.1%) and trabecular (86.2%) subtypes.
      These results were detected in the patient subgroups with initial radical
      cystectomy (p<0.01) and a primary bladder-sparing approach (p=0.02). In
      multivariate analysis of cancer-specific survival, carcinoma in situ and growth
      pattern showed statistical significance. CONCLUSIONS: Tumour invasion pattern may
      be a strong predictor of cancer-specific survival and should be considered in
      counselling patients in selecting appropriate therapy for T1G3 BC.

PMID- 19382005
TI  - Prognostic grouping of metastatic prostate cancer using conventional pretreatment
      prognostic factors.
AB  - OBJECTIVE: To develop three prognostic groups for disease specific mortality
      based on the binary classified pretreatment variables age, haemoglobin
      concentration (Hb), erythrocyte sedimentation rate (ESR), alkaline phosphatase
      (ALP), prostate-specific antigen (PSA), plasma testosterone and estradiol level
      in hormonally treated patients with metastatic prostate cancer (PCa). MATERIAL
      AND METHODS: The present study comprised 200 Finnprostate 6 study patients, but
      data on all variables were not known for every patient. The patients were divided
      into three prognostic risk groups (Rgs) using the prognostically best set of
      pretreatment variables. The best set was found by backward stepwise selection and
      the effect of every excluded variable on the binary classification cut-off points
      of the remaining variables was checked and corrected when needed. RESULTS: The
      best group of variables was ALP, PSA, ESR and age. All data were known in 142
      patients. Patients were given one risk point each for ALP > 180 U/l (normal value
      60-275 U/l), PSA > 35 microg/l, ESR > 80 mm/h and age < 60 years. Three risk
      groups were formed: Rg-a (0-1 risk points), Rg-b (2 risk points) and Rg-c (3-4
      risk points). The risk of death from PCa increased statistically significantly
      with advancing prognostic group. CONCLUSION: Patients with metastatic PCa can be
      divided into three statistically significantly different prognostic risk groups
      for PCa-specific mortality by using the binary classified pretreatment variables
      ALP, PSA, ESR and age.

PMID- 19382006
TI  - Sexual behaviour among Italian adolescents: knowledge and use of contraceptives.
AB  - BACKGROUND: Comprehensive data concerning the sexual behaviour of Italian
      adolescents are lacking; the planning of prevention programmes is therefore
      difficult. METHODS: The current study evaluates the knowledge of Italian
      adolescents about sexuality and their use of methods to prevent pregnancy and
      sexually transmitted infections. The age at first intercourse in the current
      sample was compared to that found in past samples to ascertain whether sex
      education was needed at an earlier age. The efficacy of one school-based sex
      education programme was analysed. RESULTS: Overall 630 students in three Italian
      cities were surveyed. Just over half the students were sexually active. Among
      these, the mean age at first intercourse was 15.6 years (SD +/- 1.3). The
      contraception most widely used was the condom although 'coitus interruptus',
      'natural family planning' and 'no method' were also mentioned. The knowledge
      among students from Latina, after they had received sex education, was
      significantly better. CONCLUSION: Our data show a lower mean age at first
      intercourse than has been reported for earlier periods by other authors. School
      based sexual education is effective in improving knowledge. Sexual health
      services for young people must be available and counselling services improved.

PMID- 19382007
TI  - Distractor interference in focused attention tasks is not mediated by attention
      capture.
AB  - Distractor stimuli possessing information that is relevant for a task
      (henceforth, task-relevant distractors) often interfere with task performance.
      The interference by task-relevant distractors is observed even when distractors
      are positioned outside the main attentional focus. We investigated whether such
      interference is due to an attention capture by the distractors. Participants
      responded to a target colour while ignoring word distractors positioned within
      (Experiment 1) or outside (Experiments 2 and 3) the attentional focus. The words
      carried task-relevant information in their colour and personally significant
      information in their content. Because personally significant information affects
      performance only when positioned in an attended region, it was used as a marker
      for the locus of the attentional focus. As expected, when distractors were
      attended, both task-relevant and personally significant information affected
      performance. However, when distractors were unattended, only task-relevant
      information caused interference, suggesting that attention did not shift to the
      distractors' location. We discuss possible accounts for interference effects in
      focused-attention tasks.

PMID- 19382008
TI  - Melioration behaviour in the Harvard game is reduced by simplifying decision
      outcomes.
AB  - Self-control experiments have previously been highlighted as examples of
      suboptimal decision making. In one such experiment, the Harvard game,
      participants make repeated choices between two alternatives. One alternative has
      a higher immediate pay-off than the other, but with repeated choices results in a
      lower overall pay-off. Preference for the alternative with the higher immediate
      pay-off seems to be impulsive and will result in a failure to maximize pay-offs.
      We report an experiment that modifies the Harvard game, dividing the pay-off from
      each choice into two separate consequences-the immediate and the historic
      components. Choosing the alternative with the higher immediate pay-off ends the
      session prematurely, leading to a loss of opportunities to earn further pay-offs
      and ultimately to a reduced overall pay-off. This makes it easier for
      participants to learn the outcomes of their actions. It also provides the
      opportunity for a further test of normative decision making by means of one of
      its most specific and paradoxical predictions-that the truly rational agent
      should switch from self-control to impulsivity toward the end of the experimental
      sessions. The finding that participants maximize their expected utility by both
      overcoming impulsivity and learning to switch implies that melioration behaviour
      is not due to the lure of impulsivity, but due to the difficulty of learning
      which components are included in the pay-off schedules.

PMID- 19382009
TI  - Rapid extraction of mean identity from sets of faces.
AB  - Recent evidence suggests that the notion that the visual system can rapidly
      extract summary statistics from complex scenes extends to representing sets of
      faces in terms of mean emotion or gender. Here we show that observers can also
      extract a mean identity from a set of faces with different identities. Observers
      first saw a set of four faces with different identities and were subsequently
      asked whether or not a single test face had been present in the preceding set.
      They were significantly more likely to respond that the test face had been
      present in the set if it was the morphed mean of all four set faces than when it
      was an actual set member. This finding suggests that representations based on
      summary statistics are available for face identity.

PMID- 19382010
TI  - History of early abuse as a predictor of treatment response in patients with
      fibromyalgia: a post-hoc analysis of a 12-week, randomized, double-blind, placebo
      controlled trial of paroxetine controlled release.
AB  - OBJECTIVES: We conducted a post-hoc analysis to determine whether a history of
      physical or sexual abuse was associated with response to treatment in a double
      blind, randomized, placebo-controlled trial of paroxetine controlled release (CR)
      in fibromyalgia. METHODS: A randomized, double-blind, placebo-controlled trial of
      paroxetine controlled release (CR) (dose 12.5-62.5 mg/day) was conducted in
      patients with fibromyalgia for 12 weeks. A total of 112 subjects provided
      complete information on childhood history of abuse that was recorded using the
      Sexual and Physical Abuse Questionnaire and randomized to treatments. Outcome
      evaluations in the abuse subgroup were identical to those in the entire sample.
      Health Status was determined using the 36-Item Short Form Health Survey (SF-36),
      the Sheehan Disability Scale (SDS), and the Perceived Stress Scale (PSS).
      Fibromylagia symptom severity was determined using the Fibromyalgia Impact
      Questionnaire (FIQ) and the Visual Analogue Scale for Pain (VAS). The primary
      outcome was treatment response defined as > or = 25% reduction in the FIQ-total
      score. Secondary outcomes include changes in scores on the Clinical Global
      Impression-Severity and Improvement (CGI-S and CGI-I respectively) and SF-36.
      RESULTS: The rate of childhood physical and/or sexual abuse was 52.7% (n=59). The
      baseline characteristics (health status, perceived stress, symptom severity) were
      not associated with abuse history. In logistic regression, the history of abuse
      did not predict treatment response as measured by > or = 25% reduction in FIQ
      total score (OR = 1.16, 95% CI = 1.18-1.60, P = 0.35), while the drug status
      (paroxetine CR) was significantly associated with treatment response (OR = 2.51,
      95% CI = 1.12-5.64, P = 0.02). Abuse history did not predict CGI-I (P = 0.32) or
      CGI-S (P = 0.74) improvements during treatment. After 12 weeks of treatment,
      subjects with sexual abuse history showed significantly lower mean change in
      health status (SF-36) than those without sexual abuse history (P = 0.04).
      CONCLUSIONS: Although, a significant proportion of patients with fibromyalgia
      reported a history of abuse, it does not appear to have any significant clinical
      correlates at baseline. History of abuse did not predict response to treatment in
      patients with fibromyalgia participating in a controlled trial of paroxetine
      controlled release. Prospective, well-designed studies are needed to confirm
      whether selective serotonin uptake inhibitors are effective in patients with
      fibromyalgia irrespective of their abuse history.

PMID- 19382012
TI  - Characteristics of stuttering in Dutch-speaking individuals.
AB  - Clinical diagnostic procedures to distinguish stuttering from non-stuttering
      individuals partially rely on the observation of characteristics of stuttered
      words or syllables. The purpose of this study was to examine the sensitivity and
      specificity of such a procedure, and to describe the observed characteristics of
      stuttered words. Methods involved the recording of the frequency, duration, and
      physical tension of stuttered words in conversational speech samples (total 43,
      100 words) and in an oral reading task (total 43, 100 words). In this manner, 351
      native Dutch speaking people, aged 8-53, who stutter were compared to a group of
      non-stuttering peers (n = 80). Findings suggest that applying a criterion of 3%
      stuttered words in conversational speech makes it possible to distinguish
      stuttering from non-stuttering individuals with high sensitivity (.9345) and
      perfect specificity (1.0000). Frequency, duration, and physical tension
      accompanying stuttered words are described for the group of stuttering
      participants, and these characteristics were compared to the group of non
      stuttering speakers.

PMID- 19382011
TI  - Capsular polysaccharides of cultured phototrophic biofilms.
AB  - Phototrophic biofilm samples from an Italian wastewater treatment plant were
      studied in microcosm experiments under varying irradiances, temperatures and flow
      regimes to assess the effects of environmental variables and phototrophic biomass
      on capsular exopolysaccharides (CPS). The results, obtained from circular
      dichroism spectroscopy and High Performance Liquid Chromatography, suggest that
      CPS have a stable spatial conformation and a complex monosaccharide composition.
      The total amount present was positively correlated with the biomass of
      cyanobacteria and diatoms, and negatively with the biovolume of green algae. The
      proportion of uronic acids showed the same correlation with these taxon groups,
      indicating a potential role of cyanobacteria and diatoms in the removal of
      residual nutrients and noxious cations in wastewater treatment. While overall
      biofilm growth was limited by low irradiance, high temperature (30 degrees C) and
      low flow velocity (25 l h(-1)) yielded the highest phototrophic biomass, the
      largest amount of CPS produced, and the highest proportion of carboxylic acids
      present.

PMID- 19382013
TI  - A linguistic communication measure for monitoring changes in Chinese aphasic
      narrative production.
AB  - This study investigated the usefulness of the Cantonese Linguistic Communication
      Measure (CLCM) in monitoring changes of narrative production in five Chinese
      adults with aphasia in the period of spontaneous recovery (SR group) and four who
      underwent anomia therapies (Tx group). Language samples elicited from a picture
      description task were collected among SR participants at regular intervals within
      the first 6 months post-onset and among Tx participants before and after
      treatment. Results showed that the CLCM indices could reflect changes of language
      production in these individuals over time. The changes of index values were
      consistent with the expectations of performance during early stages after stroke
      for the SR participants and treatment outcomes of the Tx participants. While the
      CLCM has previously been shown to be useful in measuring aphasic narratives on a
      single occasion, this study has provided further evidence of its capability to
      monitor changes of language production over time.

PMID- 19382014
TI  - Effects of neurological damage on production of formulaic language.
AB  - Early studies reported preserved formulaic language in left hemisphere damaged
      subjects and reduced incidence of formulaic expressions in the conversational
      speech of stroke patients with right hemispheric damage. Clinical observations
      suggest a possible role also of subcortical nuclei. This study examined formulaic
      language in the spontaneous speech of stroke patients with left, right, or
      subcortical damage. Four subjects were interviewed and their speech samples
      compared to normal speakers. Raters classified formulaic expressions as speech
      formulae, fillers, sentence stems, and proper nouns. Results demonstrated that
      brain damage affected novel and formulaic language competence differently, with a
      significantly smaller proportion of formulaic expressions in subjects with right
      or subcortical damage compared to left hemisphere damaged or healthy speakers.
      These findings converge with previous studies that support the proposal of a
      right hemisphere/subcortical circuit in the management of formulaic expressions,
      based on a dual-process model of language incorporating novel and formulaic
      language use.

PMID- 19382015
TI  - Text comprehension in Down syndrome: the role of lower and higher level
      abilities.
AB  - The contribution of lower level linguistic abilities (study 1) and a higher level
      capacity, namely the use of context, (study 2), on text comprehension was
      studied. Participants were 16 individuals with Down syndrome aged between aged
      between 8 years 11 months and 16 years 10 months, and 16 children with typical
      development, aged between 5 years 11 months and 7 years 3 months, matched for the
      level of text comprehension. In study 1 the two groups were compared for
      receptive vocabulary and sentence comprehension: both of them were shown to play
      a role in text comprehension in Down syndrome. Since participants with Down
      syndrome had very low scores in sentence comprehension, study 2 tested the
      hypothesis that when sentences were presented within a brief context, individuals
      with Down syndrome would perform better. This hypothesis was confirmed and it was
      shown that contextual facilitation was closely related to text comprehension
      skills.

PMID- 19382016
TI  - Speed and accuracy of rapid speech output by adolescents with residual speech
      sound errors including rhotics.
AB  - Children with residual speech sound errors are often underserved clinically, yet
      there has been a lack of recent research elucidating the specific deficits in
      this population. Adolescents aged 10-14 with residual speech sound errors (RE)
      that included rhotics were compared to normally speaking peers on tasks assessing
      speed and accuracy of speech production. The two groups were evaluated on an oral
      diadochokinetic task, which required rapid production of the trisyllable /p
      Lambda t Lambda k Lambda/, and two rapid naming tasks: monosyllabic letter names
      and multisyllabic picture names. No significant group differences were observed
      in the speed of trisyllables on the DDK task, whether examining all attempts or
      only correct productions. However, the RE group was less accurate and more
      variable in their production of the trisyllables. In addition, the RE group was
      slower and phonologically less accurate in rapidly naming multisyllabic pictures,
      but not in naming letters. A combination of speed and accuracy measures from
      these tasks revealed relatively little overlap between groups. Results suggest
      that both speed and accuracy may be impaired in adolescents with RE, although the
      underlying causal mechanisms require further exploration.

PMID- 19382017
TI  - Bilateral paediatric cochlear implants: a critical review.
AB  - A recent trend has been the implantation of bilateral cochlear implants (CIs) for
      children with severe to profound hearing loss. A review of available research on
      bilateral CIs was conducted to determine the support for this trend. A replicable
      review was undertaken to evaluate published research studies that examined the
      effectiveness of bilateral paediatric cochlear implantation. Databases, reference
      lists, and journals were searched for relevant documents using a pre-determined
      search protocol. Twenty-nine articles met the review's inclusion criteria and
      were retrieved and reviewed. This review adds to the previously published reviews
      on the topic by identifying additional paediatric studies. Sound localization and
      speech recognition in noise appear to be improved with bilateral compared to
      unilateral cochlear implants. Similarly, evoked potential measures suggest
      improved morphology when the second CI is implanted early. Well-designed and
      controlled studies that explore a variety of outcomes including cost
      effectiveness, quality of life, speech, language, and psycho-educational measures
      should be further explored in order to provide additional support for parents and
      clinicians confronted with the bilateral cochlear implant decision.

PMID- 19382018
TI  - Evaluation of a frequency transposition algorithm using wearable hearing aids.
AB  - Transposition of acoustic information from higher to lower frequencies may help
      people with severe or profound high-frequency hearing loss, especially when a
      'dead region' is present. Previously, we (Robinson et al, 2007 ) evaluated the
      benefit of an FFT-based transposition algorithm in a laboratory study. Although
      results were promising, we hypothesized that further training and exposure would
      be needed to gain the full benefit. This was tested here by implementing the
      algorithm in wearable digital hearing aids. Five subjects with high-frequency
      dead regions used the aids for five weeks. Performance on the transposing and
      control conditions was compared objectively using speech tests (vowel-consonant
      vowel, 's' detection, and speech in noise) and subjectively using questionnaires.
      Overall, the results showed no benefit with the transposition even after
      experience. Subjective preference was generally for the control condition.

PMID- 19382019
TI  - Effect of (211)At alpha-particle irradiation on expression of selected radiation
      responsive genes in human lymphocytes.
AB  - PURPOSE: Analysis of the relative expression of radiation responsive genes
      (previously shown to respond to gamma-radiations) after exposure of human
      lymphocytes to (211)At alpha-particles and the suitability of these genes as
      potential markers for alpha-biodosimetry. MATERIALS AND METHODS: Lymphocytes
      isolated from the peripheral blood of two healthy human donors were exposed in
      triplicate for 30 min to different concentrations of Na(211)At at 37 degrees C
      (absorbed doses: 0.05-1.6 Gy). Following an incubation period (2 h), the total
      RNA was isolated from the irradiated lymphocytes and the relative expression of
      the following 18 genes was tested for change using TaqMan probes based upon the
      real-time quantitative polymerase chain reaction. METHOD: BBC3 (B-cell lymphoma 2
      binding component 3), CD69 (cluster of differentiation 69), CDKN1A (cyclin
      dependent kinase inhibitor 1A), DUSP8 (dual specificity phosphatase 8) EGR1
      (early growth response 1), EGR4 (early growth response 4), GADD45A (growth arrest
      and DNA-damage-inducible, alpha), GRAP (growth factor receptor-bound protein 2
      related adaptor protein), LAP1B (TOR1AIP1; torsin A interacting protein 1), IFNG
      (interferon gamma), ISG20L1 (interferon-stimulated exonuclease gene 20kDa - like
      1), c-JUN (jun oncogene), MDM2 (mouse double minute 2), PCNA (proliferating cell
      nuclear antigen), PLK2 (polo-like kinase 2), RND1 (rho family GTPase 1), TNFSF9
      (tumour necrosis factor superfamily member 9) and TRAF4 (tumour necrosis factor
      receptor-associated factor 4). RESULTS: The expressions of the 18 genes, except
      GRAP, were up-regulated following exposure to alpha-radiation. A comparison of
      the results of two individuals tested here showed great variability. Dependence
      of gene expression upon alpha-dose was observed in certain dose intervals for
      BBC3 (R(2) = 0.61 [individual 1] / 0.81 [individual 2], significance 0.2-1.6 Gy
      [1] / 0.05-0.1 Gy [2]) and MDM2 (R(2) = 0.78/0.54; 0.8-1.6 Gy [1], 0.05-0.1 Gy
      [2]) genes in both individuals. Additionally, for individual 1 the dose
      dependence was found for the following genes: ISG20L1 (R(2) = 0.69, 0.05-0.1 Gy),
      PCNA (R(2) = 0.59, 0.8-1.6 Gy) and IFNG (R(2) = 0.74 up to 0.4 Gy, 0.05-0.1 Gy).
      CONCLUSION: Candidate genes for a possible role in future early-phase (2 h) alpha
      biodosimetry are BBC3, ISG20L1, MDM2, PCNA and IFNG.

PMID- 19382020
TI  - Cancer stem cells and radiotherapy.
AB  - PURPOSE: The present work summarises the history and current status of research
      into the importance of cancer stem cells for radiobiological research and for
      clinical radiation oncology. An effort is made to differentiate clonogenicity
      from stemness of cancer cells. CONCLUSION: In radiooncology, cancer stem cells
      have been an important research field for five decades. Quantitative
      transplantation assays with evaluation of the take dose 50% (TD50) remain the
      gold standard to verify the stemness of the selected cells. New technologies
      allow sorting of tumour cells according to their surface marker expression and
      thereby selecting subpopulations that are enriched in cancer stem cells (e.g.,
      CD133, CD44, CD29). While development of surface-marker-based assays is a highly
      important step in cancer-stem-cell research, to date there are still problems to
      be solved, e.g., the specifity of markers, adequate animal models, and optimised
      in vitro assays. Of special concern for radiobiology is that clonogenic in vitro
      assays do not necessarily measure stemness of cancer cells. This hampers
      investigations into the important question of whether cancer stem cells are more
      radioresistant than non-stem cells. The most extensive of the limited data on
      this topic relate to glioma stem cells identified by the surface marker CD133.
      These do not provide firm evidence for difference of radiosensitivity between
      stem and non stem cells. In spite of many problems to be solved, the combination
      of stem cell markers with radiobiological assays bears considerable promise for
      advancing translational research in radiation oncology.

PMID- 19382021
TI  - Effects of low fluences of radiations found in space on cellular systems.
AB  - PURPOSE: In recent years, there has been a large increase in the amount of space
      related radiation biology research being conducted. This review will discuss
      selected issues related to cellular responses to the types of radiations found in
      space, with emphasis on comparison of cellular effects from high versus low
      linear energy transfer (LET) radiations and on effects that might be expected to
      predominate at the low radiation fluences characteristic of space, e.g.,
      bystander effects and adaptive responses. CONCLUSIONS: Space radiation is unique
      and complex, being composed of galactic cosmic rays and solar particles. Not
      surprisingly, space radiation biology is also unique and complex. Responses in
      cells traversed by high atomic number, high energy (HZE) particles are different,
      at least in part, from the responses of cells exposed to low LET photons not just
      quantitatively but also qualitatively. This is illustrated by discussion of four
      sets of data - clustering of DNA damages, foci of DNA repair-related proteins,
      chromosome aberrations and gene expression. 'Non-targeted' effects, particularly
      bystander responses, may have increased importance in cellular responses to space
      radiation because of the very low fluences and fluence rates as well as the non
      homogeneous dose distributions from HZE particles compared to the more
      homogeneous distributions of the photon radiations usually encountered on Earth.
      Likewise adaptive responses could be expected to play a role in cellular damages
      at the low particle fluences characteristic of space. The growing number of
      ground-based studies being performed with energetic protons and heavy ions should
      lead to greatly expanded knowledge of the impact of the space radiation
      environment on astronauts.

PMID- 19382022
TI  - From the editor.

PMID- 19382023
TI  - Geriatric social work career tracking: graduates of the Hartford Partnership
      Program for Aging Education (HPPAE).
AB  - Despite a growing need for geriatric social workers, there is a question as to
      whether MSW graduates who are gerontologically prepared actually enter the
      workforce to serve older adults. By tracking MSW graduates who had special
      training in aging, this study aims to explore their job search and career
      experience. Findings show that most graduates located aging-related jobs 4 months
      postgraduation and remained committed to the field 1 to 2 years later. The
      majority were working in direct service provision in clinical settings. Their
      salaries compare favorably with those of generic social workers. Implications for
      geriatric social work education are discussed.

PMID- 19382024
TI  - Geriatric enrichment in social work education: lessons learned from the GeroRich
      projects.
AB  - The Geriatric Enrichment in Social Work Education (GeroRich) initiative was a
      critical step in addressing the national shortage of social workers interested in
      gerontological practice. Sixty-seven social work programs participated in the 3
      year GeroRich project designed to infuse gerontological content into the BSW and
      MSW curriculum. This study analyzed the lessons learned by participating
      institutions about the curriculum enrichment effort. Five themes emerged from the
      qualitative analysis of GeroRich final reports: (a) obtaining faculty buy-in and
      faculty development, (b) increasing student interest and engagement, (c)
      developing community partners, (d) developing interdisciplinary linkages, and (e)
      facilitating institutional commitment and sustainability. The findings from this
      study provide valuable information on the implementation of curricular enrichment
      efforts in gerontology that can benefit social work and other health care
      disciplines.

PMID- 19382025
TI  - Family influence on caregiver resistance, efficacy, and use of services in family
      elder care.
AB  - This research investigated how resistance to use of services attributed to family
      members and primary caregiver self-efficacy and resistance influenced actual use
      of services. Data were analyzed from questionnaires completed by 224 persons
      engaged in informal elder care in the community. Tests of 6 hypotheses revealed
      that family influence on caregivers had a consistent, important influence on
      behavior and views of caregivers. Family resistance to use of formal services
      framed caregivers' feelings, preferences, and decisions ranging from their own
      perceived self-efficacy to actual obtainment of help outside the family.
      Professionals must include family members in their dialogue with primary
      caregivers about their plans for elder care. Suggestions for interventions to
      better understand family and caregiver resistance are discussed.

PMID- 19382026
TI  - Eleven tips to lighten the load: optimizing the blessing of family caregiving.
AB  - This informal piece offers tips to family caregivers, based on my personal
      experience as a social work educator who temporarily moved in with my mother, who
      lives with dementia. Lessons learned are distilled into 11 tips that are
      respectfully offered to other social work educators who have the blessing and the
      challenge of caring for their older loved ones.

PMID- 19382027
TI  - The influence of service factors on spousal caregivers' perceptions of community
      services.
AB  - The literature clearly denotes that spouses differ from other family members in
      their reactions to caregiving, their patterns of service use and their assessment
      of specific services. Yet, despite their prevalence as caregivers, little is
      known about their unique perceptions of community services and the factors that
      impact their experiences with the service system. The purpose of this study was
      to explore the relative influence of (a) spouses' personal factors (e.g., gender,
      family support) and (b) service factors (e.g., one-on-one professional support),
      on spousal caregivers' perceptions of community services. The study employed a
      survey design with a sample of 73 spousal caregivers caring for their partners
      with dementia at home. This study found that spousal caregivers have more
      negative perceptions of the service system when their in-home workers are not
      informed about their spouses' likes, dislikes and routines. This service factor
      was the most significant predictor of caregivers' service perceptions. The study
      further found that most spousal caregivers receive fewer than five consultations
      from a non-medical professional over a one year period. While spouses longed for
      more professional support, this service factor was not uniquely associated with
      service related stress. The policy and practice implications of these findings
      are discussed.

PMID- 19382028
TI  - A comparison of rural and urban older adults in Iowa on specific markers of
      successful aging.
AB  - This study examines the differences between rural and urban older adults on level
      of life satisfaction and depressive symptoms, focusing on the effect of social
      support. Data were collected through structured interviews at senior centers and
      senior meal sites in eastern and southeastern Iowa. The Duke Social Support Index
      (DSSI), the Life Satisfaction Index-Z (LSI-Z), and the Geriatric Depression Scale
      15 (GDS15) were used. Correlations (Pearson's r), independent sample t-tests, and
      multiple regression were computed. Findings indicated that urban residents
      reported more depressive symptoms, as compared to rural residents. Subjective
      level of social support was a stronger predictor of life satisfaction and was
      more negatively related to depressive symptoms among rural than among urban older
      adults. Results suggest that social workers who work with aging people need to be
      aware of rural-urban differences in mental health. Furthermore, social workers
      need to have knowledge of older adults' social networks and work to ensure
      greater opportunity for social interaction.

PMID- 19382030
TI  - Estimating the longitudinal association between adolescent sexual behavior and
      exposure to sexual media content.
AB  - The purpose of this study is to estimate the association between adolescent
      sexual behavior and exposure to sexual media content. A three-wave, longitudinal
      survey sample (N = 506) of 14- to 16-year-olds at baseline is analyzed using
      growth curves. Growth trajectories are linear for sexual behavior but not for
      exposure to sexual media content. The signs of the exposure slopes are not
      uniformly positive: Hispanic and African American respondents show declines of
      exposure to sexual media content over the age range investigated here. Although
      changes in exposure to sex content are highly associated with changes in sexual
      behavior among Whites, there is little or no association between changes in these
      variables among Blacks.

PMID- 19382031
TI  - Thrombolytics for hyperacute stroke in children.
AB  - Intravenous tissue plasminogen activator (tPA) has changed the landscape of acute
      stroke care in adults, but remains unstudied in children. Developmental
      differences in both stroke etiologies and the hematologic system may alter the
      risk benefit ratio of this drug when applied to stroke in children.

PMID- 19382032
TI  - Hemorheological parameters in children with iron-deficiency anemia and the
      alterations in these parameters in response to iron replacement.
AB  - AIM: Iron-deficiency anemia (IDA) is a common disorder in pediatric patients.
      There are a limited number of studies having controversial results in
      investigating red blood cell (RBC) deformability and aggregation in adult IDA
      patients. The aim of this study is to determine the change of hemorheological
      parameters, including RBC deformability, aggregation, and plasma and whole blood
      viscosity, in children with IDA following iron supplementation therapy. MATERIALS
      AND METHODS: The study was performed on 20 children with IDA (average age 35.5 +/
      6.5 months) and 20 age-matched healthy children. The anemia group was treated
      with 5 mg/kg/day peroral iron for 2 months. Hematological and hemorheological
      parameters were determined before and after treatment. An ectacytometer was used
      for the assessment of RBC deformability and aggregation and a cone-plate
      rotational viscometer for plasma and whole blood viscosities. Hematological
      parameters were determined using an electronic hematology analyzer. RESULTS:
      Although IDA resulted in a decrement in RBC deformability, aggregation, plasma,
      and whole blood viscosities, these parameters returned to control values after
      iron supplementation therapy. Serum ferritin levels and hematological parameters
      (Hb, MCV, MCH, MCHC) that were lower in IDA patients were also found to be
      increased after treatment. CONCLUSION: Iron treatment not only reverses the
      symptoms of anemia but also may contribute to blood flow regulation by causing
      increments in the alterations observed in hemorheological parameters during
      anemia.

PMID- 19382034
TI  - Hypereosinophilic syndrome in childhood: clinical and molecular features of two
      cases.
AB  - Hypereosinophilic syndrome (HES) represents a heterogeneous group of diseases,
      some of which are being clarified by recent advances in molecular genetics. It is
      very rare in children. Uncertainties in classification and lack of prospective
      studies make therapeutic decisions difficult. The authors report two cases of HES
      in which steroid therapy was effective.

PMID- 19382033
TI  - Haploidentical hematopoietic stem cell transplantation in child hematologic
      malignancies with G-CSF-mobilized marrow grafts without T-cell depletion: a
      single-center report of 45 cases.
AB  - In this report, the authors describe a protocol for haploidentical bone marrow
      transplantation in children who received G-CSF-mobilized bone marrow grafts
      without T-cell depletion from HLA-mismatched parents. Forty-two of 45 patients
      achieved complete donor hematopoietic engraftment; the medium time for neutrophil
      and platelet recovery was 17 and 19 days, respectively. Three died of early
      transplantation-associated complications; other causes of death included relapse
      (11 cases), fungal pneumonia (5), and acute graft-versus-host disease (2). The
      total disease-free survival rate longer than 2 years was 53.3%. These data
      suggest that haploidentical hematopoietic transplantation is an alterative
      strategy for children who lack immediate access to HLA-matched sources.

PMID- 19382035
TI  - The case of a 1-year-old girl with hereditary hyperferritinemia cataract
      syndrome.
AB  - Hereditary hyperferritinemia cataract syndrome (HHCS) is an autosomal dominant
      disorder characterized by high serum ferritin levels in the absence of iron
      overload accompanied by early onset of bilateral cataracts. The authors report
      the case of HHCS in a 1-year-old girl in a family of German origin. Routine blood
      examination revealed serum ferritin levels up to 2530 microg/L. Slit-lamp
      examination showed bilateral cataracts. HHCS should be considered in cases of
      high serum ferritin level and bilateral cataracts, which can even occur in
      pediatric patients. A liver biopsy and bone marrow aspiration are unnecessary
      diagnostic procedures in cases of HHCS and repeated phlebotomies are harmful.

PMID- 19382036
TI  - Anaplastic large cell lymphoma with primary involvement of skeletal muscle: a
      rare case report and review of the literature.
AB  - Primary skeletal muscle ALCL is very rare. Here the authors report a case of
      skeletal muscle ALCL that was proven pathologically. A 14-year-old boy presented
      with a persistent fever, chills, night sweats, headache, and significant weight
      loss. A CT scan of the abdomen showed a hazy mass about 3.2 x 1.2 cm in his left
      sacrospinalis. Ultrasonography revealed a low-echo and irregular mass in the left
      lumbar muscle measuring 8 x 1.4 x 3.6 cm in size and a similar mass 8 x 3.5 x 3.7
      cm in size in the femoral muscle of the left thigh. MRI demonstrated an abnormal
      mass signal 4 x 3 x 9 cm in size infiltrating the left sacrospinalis muscle. The
      biopsy specimen was taken from the femoral muscle of the left thigh at surgery.
      Histopathological examination revealed a diffuse infiltration of large and
      atypical cells with pleomorphic nuclei and abundant cytoplasm. Immunohistological
      staining showed these atypical cells were positive for CD30 (Ki-l), anaplastic
      lymphoma kinase (ALK), epithelial membrane antigen (EMA), CD3, CD45RO, and CD68.
      The morphology and immunophenotype were consistent with CD30-positive, ALK
      positive, and ALCL of T-cell lineage. The patient's condition was diagnosed as
      CD30-positive primary skeletal muscle ALCL.

PMID- 19382037
TI  - Poland syndrome with intracranial germ cell tumor in a child.
AB  - Poland syndrome is an uncommon unilateral deformity of chest wall and upper
      extremity with variable manifestations. Although numerous case reports of Poland
      syndrome associated with malignancies have been published, intracranial germ cell
      tumor in Poland syndrome has not been previously reported. The authors describe a
      15-year-old male patient with intracranial germ cell tumor and Poland syndrome.

PMID- 19382038
TI  - Autobiographical memory and amnesia: using conceptual knowledge to ground the
      self.
AB  - A case of retrograde amnesia, PJM, elucidated the relationship between self,
      episodic memory and autobiographical knowledge. Results from a variety of
      measures including the I Am Memory Task (IAM Task), where memories are cued by
      self-generated self concepts, demonstrate that PJM has a coherent, continuous
      sense of self, despite having lost episodic memories for an 18-month period. Her
      use of conceptual autobiographical knowledge, in episodic tasks and to support
      aspects of identity, shows how autobiographical knowledge can support the self
      when episodic memories are inaccessible. These results are discussed with
      relation to current neuropsychological models of self and memory.

PMID- 19382040
TI  - [Usage of marginal organs for liver transplantation: a way around the critical
      organ shortage?].
AB  - The transplantation of marginal organs or those meeting the so-called extended
      donor criteria (EDC) is today a significant option to alleviate the low
      availability or organs and to increase the number of transplantation which in
      turn is -accompanied by a lower mortality among wait-ing-list patients. However
      such an extension of the spender pool carries the risks of an increased incidence
      of organ dysfuntions and a higher recipient mortality. This situation presents an
      ethical problem when marginal organs are accepted for transplantation because the
      anticipated mortality for the individual recipient cannot be determined. The
      transplantation of marginal organs from -donors with a high MELD score seems to
      be linked to a higher mortality. In particular, the combina-tions of high donor
      age and long ischaemic time or advanced donor age and hepatitis C infection in
      the recipient are definitively associated with a significantly poorer organ
      survival rate. In view of the serious lack of organs, efforts should be made, for
      example, by shortening of the is-chae-mic time and the development of therapeutic
      strategies, to improve the function and increase the number of usable marginal
      organs and thus to increase pool of donor organs. The refusal of marginal organs
      on the basis of individual EDC without consideration of the status of recipient
      does not seem to be adequate.

PMID- 19382039
TI  - The emergence of cognitive discrepancies in preclinical Alzheimer's disease: a
      six-year case study.
AB  - We present neuropsychological data from an 81-year-old individual who was
      followed over a six-year period, initially as a healthy control participant. She
      performed above age-adjusted cutoff scores for impairment on most
      neuropsychological tests, including learning and memory measures, until the final
      assessment when she received a diagnosis of probable Alzheimer's disease (AD).
      Despite generally normal scores on individual cognitive tests, her cognitive
      profile revealed increasingly large cognitive discrepancies when contrasting
      verbal versus visuospatial tasks, and complex versus basic-level tasks. The
      present case provides intriguing evidence that cognitive-discrepancy measures
      could improve our ability to detect subtle changes in cognition at the earliest,
      preclinical stages of AD.

PMID- 19382041
TI  - [Technique of pancreatogastrostomy after pancreaticoduodenectomy].
AB  - A broad spectrum of different techniques for anastomosing the pancreatic remnant
      after the Kausch-Whipple procedure has been published. Most commonly used is the
      pancreaticojejunostomy, preferably in an end-to-side and duct-to-mucosa fashion.
      Utilisation of the posterior gastric wall represents an interesting alternative,
      which is being increasingly discussed in the literature. Two current meta
      analyses and three prospective, randomised trials have proved the comparability
      of the two procedures. Accordingly, our own data show corresponding results
      regarding mortality and morbidity using this anastomosis. We personally prefer a
      purse-string suture for fixation of the pancreatic remnant, which seems to be
      more easily and more rapidly performed than application of interrupted sutures.

PMID- 19382042
TI  - [Management of cholecysto- and choledocholithiasis--survey and analysis of 16 615
      cholecystectomies and common bile duct explorations in bavaria].
AB  - BACKGROUND AND METHODS: The aim of this study was the evaluation of the
      management of cholecysto- and choledocholithiasis and outcome of -laparoscopic as
      well as open cholecystectomy (CHE) and common bile duct (CBD) exploration in
      Bavaria, Germany. A written questionnaire -in-cluding 201 structured items was
      sent to all 180 hospitals and departments performing gen-eral or abdominal
      surgery in Bavaria. RESULTS: The response rate was 60 %. A total of 16 615
      operations for gallstone disease including 16 051 cholecystectomies and 453 CBD
      explo-ra-tions with or without cholecystectomy were -reported. 88 % of all
      cholcystectomies started -laparoscopically, the conversion rate was 5.6 %. The
      Veres needle (69 %), 4 trocar techniques and electrosurgical hook knife were
      reported as standard procedures. A retrieval bag was used by 53 % of all
      surgeons. The overall complication rate for cholecystectomy was 5.46 % including
      0.15 % -major bile duct injuries. Relaparoscopy was performed in 0.35 %,
      relaparotomy in 0.44 % and postoperative treatment by ERC in 1.45 %. The overall
      hospital mortality rate was 0.13 %. When choledocholithiasis was suspected, a two
      stage management ("therapeutic splitting") with preoperative ERC was preferred
      (99 %). The conversion rate of simultaneous laparoscopic CHE+CBD exploration was
      43 %. CONCLUSION: These results allow an estimation of the frequency and overall
      risks in surgical therapy for gallstones. At present, new techniques like
      combined laparoscopic and endoscopic proce-dures, microinstruments or N.O.T.E.S
      do not play a significant role in Germany.

PMID- 19382043
TI  - [Hepatic resection for hepatocellular carcinoma--results and analysis of the
      current literature].
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth-leading cause of cancer
      death world-wide. Although less frequent in Western Europe, its incidence is
      increasing in this region. Causes involved in the pathogenesis of HCC are,
      besides viral hepatitis, metabolic and nutritional factors (alcohol, diabetes,
      obesity). The therapeutic management depends strongly on the initial extent of
      disease and includes hepatic resection, liver transplantation and local ablation.
      In this context, we present our results on liver resection for HCC and a
      discussion of the current literature about (potentially curative) treatment for
      HCC. PATIENTS: From 1999 until 2008 93 patients [83 % male, median age 64 (range:
      39-94) years] underwent hepatic resection for HCC. Postoperative follow-up was
      available in 85 patients [median follow-up: 1.2 (0.25-8) years]. RESULTS: In
      contrast to data, especially from Asia, a viral hepatitis as the origin of HCC
      was found in only 28 % of the patients in our series. Half of the patients had
      proven liver cirrhosis. The median number of intrahepatic tumours was one (1-11),
      median size of the largest tumour was 55 mm (5-250 mm). 58 % of the HCC were
      removed by atypical or segmental resection, 42 % of the patients underwent
      hemihepatectomy or extended -hemihepatectomy. Tumor-free resection margins were 
      achieved in 95 %. Total postoperative morbidity was 61 %. A reoperation for
      complications was -necessary in 10 %. Hospital mortality was 8.6 % in the entire
      study period but decreased from 14.9 % in 1999-2004 to 2.2 % in 2005 to 2008 (p =
      0.03). Actuarial survival was 81 % after 1 year, 58 % after 3 years and 26 %
      after 5 years. The T-stage could be identified tendentially as a prognostic
      factor influencing survival. CONCLUSION: With the proper selection of patients,
      liver resection for HCC may be performed with a curative intention (i. e., free
      resection margins) in over 90 %. Although it decreased during the study period
      peri-operative mortality was higher than after resection of other hepatic
      tumours. Long-term survival in our series was comparable to reports from other
      European centres.

PMID- 19382044
TI  - [Surgical treatment of benign liver tumours--indications and results].
AB  - The authors present their results on the treatment of benign liver tumors. 65
      patients were operated upon in the University Hospital in Pil-sen from 2000 until
      July 2006. Benign liver lesions were rather rare compared to malignant tumours,
      for which 273 patients were treated within the same period. The most often found
      benign -lesions were hepatocellular adenoma, focal nodular hyperplasia (FNH) and
      hemangioma. Sometimes, it was not possible to make a correct diagnosis
      preoperatively. The surgical procedures used for benign tumours were mostly
      enucleation and non-anatomic parenchyma-saving resection (55.4 %). Morbidity in
      this group was 26.5 %, mortality 0 %.

PMID- 19382045
TI  - [Radiofrequency ablation of colorectal liver metastases].
AB  - INTRODUCTION: Liver resection is the preferred treatment for colorectal liver
      metastases. About 30 to 40 % of the patients survive for five years after radical
      resection of liver metastases. In contrast to that, patients who are not fit
      enough for radical resection of metastases and two are treated by chemotherapy
      survive only for 18 months on average. The survival of patients with non
      resectable liver metastases can be improved by metastases destruction and
      subsequent chemotherapy. At present, radiofrequency ablation (RFA) is widely used
      for the destruction of liver tumours. PATIENTS AND METHODS: In the four-year
      period (2000-2003), 190 patients with liver metastases of colorectal carcinoma
      have been operated upon at the 2 (nd) Surgical Department of University Hospital
      in Olomouc. Radical resection of metastases was carried out in 136 patients (71.5
      %), RFA combined with liver resection was performed in 23 patients (12 %) and
      exclusive RFA of metastases was indicated in 31 patients (16 %). The patients
      were evaluated for the disease-free survival after one year and the survival
      rates at 12, 24 and 36 months after operation were determined. RESULTS: 12 months
      after the operation no tumour progression was found in 115 patients (85 %)
      subjected to radical resection of liver metastases, in 16 patients (52 %) after
      sole RFA of metastases and in 15 individuals (65 %) who underwent liver
      metastasis resection combined with RFA of the remaining cancer foci. The survival
      of patients after 12, 24 and 36 months was 124 / 136 (91 %) 103 / 136 (76 %) and
      79 / 136 (58 %) in the group of radical metastasis resection; after sole RFA of
      the metastases and subsequent chemotherapy, the survival at 12, 24 and 36 months
      amounted to 27 / 31 (87 %), 19 / 31 (61 %) and 8 / 31 (26 %) of the patients; in
      the group undergoing metastases resection combined with RFA and adjuvant
      chemotherapy patient survival at 12, 24 and 36 months was as follows: 19 / 23 (83
      %), 13 / 23 (57 %), and 7 / 23 (30 %). CONCLUSION: RFA combined with adjuvant
      chemotherapy considerably extends the survival of patients with liver metastases
      of colorectal carcinoma compared to chemotherapy alone. However, no difference in
      survival was found between our patients subjected to RFA of metastases and
      adjuvant chemotherapy and those patients undergoing resection of liver metastases
      combined with RFA of unresectable metastases and subsequent chemotherapy.

PMID- 19382046
TI  - [Symptomatic non-parasitic liver cysts: early and long-term results of surgical
      management].
AB  - BACKGROUND: Symptomatic congenital cysts of the liver, whether solitary or
      multiple in appearance, can be treated by a laparoscopic approach. Here we
      present our single centre experience encompassing a rather large cohort of
      patients. PATIENTS AND METHODS: From our prospective surgical database,
      introduced for quality management and surveillance, we identified 34 consecutive
      patients who were operated on for congenital liver cysts between 1995 and 2004.
      Using a questionnaire, the patients were contacted to assess actual complaints,
      the recurrence of operated cysts or the frequency of newly developed cysts.
      During follow-up two patients had died of other diseases. Of the remaining 32
      patients 30 answered the questionnaire (94 %). The median postoperative follow-up
      was 55 months (range: 8-121). RESULTS: There were 29 women and 5 men with
      solitary (n = 10) or multiple (n = 20) liver cysts and polycystic liver disease
      (n = 4), all complained of unspecific upper abdominal pain. Due to previous
      operations or coexisting diseases open laparotomy was performed in 7 patients and
      laparoscopic unroofing was performed in 27 patients. The conversion rate to open
      laparotomy was 7 % (n = 2). Solitary cysts were unroofed in 25 patients and
      multiple cysts in 8 patients. The resected cysts had a median diameter of 10.5 cm
      (solitary cysts: 7-19 cm, multiple cysts: 4-23 cm). The only postoperative
      complications were 3 cases of bilioma (8.9 %), which required open revision in
      one case. There were no cysts recurrences, but persisting upper gastrointestinal
      pain, backache or problems arising from the scars were reported by 9 patients (30
      %). CONCLUSION: In cases of symptomatic congenital liver cysts laparoscopic
      unroofing should be considered the treatment of choice.

PMID- 19382047
TI  - [How safe is laparoscopic cholecystectomy?].
AB  - INTRODUCTION: Laparoscopic cholecystectomy (LCE) is the standard treatment for
      symptomatic non-complicated cholecystolithiasis. However, there is still an
      ongoing debate about the appropriate surgical approach in cases with complicated
      cholecystolithiasis. As a result, an initial decision whether to use the open or
      laparoscopic approach must be primarily based on patient safety. Additional
      indications favouring the use of LCE must not lead to an increase in the rate of
      serious complications. METHODS: All patients who underwent operations for
      cholecystolithiasis performed in a single surgical centre, from 1 / 1 / 1994 to
      12 / 31 / 2007, were considered in this analysis. Parameters for the
      characterisation of the results were intervention-associated hospital mortality
      and iatrogenic transsection of the common bile duct. RESULTS: 5 084
      cholecystectomies were performed during the study period, 84 % (n = 4 272)
      intended as laparoscopic and 16 % (n = 812) as open procedures. The LCE
      operations were done by 36 surgeons. The conversion rate to open surgery was 6.2
      % (n = 265), in cases of acute cholecystitis, however, it was 26.3 % (n = 86).
      One LCE procedure involved an iatrogenic bile duct transsection (0.02 %). The in
      hospital mortality rate for LCE was 0.05 % (n = 2). CONCLUSIONS: In the hands of
      experienced surgeons LCE is a safe procedure for the treatment of symptomatic,
      non-complicated cholecystolithiasis. Associated with complicated
      cholecystolithiasis however are an increase in conversion rate and thus the risk
      of severe complications.

PMID- 19382049
TI  - [Pancreatic surgery in a regional hospital].
AB  - BACKGROUND: Recently it was shown that in several surgical procedures the case
      load of an institution correlated in direct proportion with the outcome.
      Therefore, the German authorities with effect from January 1, 2008 have defined
      the minimum case load per year of an institution for selected surgical procedures
      in order to increase the medical quality and improve the outcome. Until now,
      however, there is no experience in establishing a medical centre for pancreatic
      surgery according to these regulations. The aim of this study was, therefore, to
      describe the possibilities and the prerequisites necessary to establish a new
      pancreatic centre according to the requirements of the German official
      regulations. PATIENTS AND METHODS: In a prospective clinical study, the data of
      269 patients who underwent a resective surgical procedure for pancreatic diseases
      between May 1998 and August 2007 were analysed. All included patients underwent a
      defined surgical procedure for malignant and benign lesions of the pancreatic
      gland. Indication for operation, operative procedure, postoperative morbidity and
      mortality were analysed in this study. RESULTS: After the year 2000, the annual
      case load of pancreatic resections per year amounted to over 30 patients. In most
      cases (n = 127) the indication for operation was a malignant disease of the
      pancreatic head, in 94 cases the patients were operated for chronic pancreatitis
      with a benign tumour of the pancreatic head. In most cases (n = 106) a pylorus
      preserving partial duodenopancreatectomy was performed followed by the duodeno
      preserving pancreatic head resection (Beger procedure, n = 55). The overall
      complication rate amounted to 30.2 %, overall mortality 0.7 %. Two patients died
      on the 37 (th) and 44 (th) day postoperatively. CONCLUSIONS: The establishment of
      a medical centre for pancreatic surgery is possible according to the regulations
      of the German authorities. Nevertheless, there are multiple factors influencing
      medical quality apart from the case load of a hospital. These are a well
      functioning intensive care unit and the possibility for radiological and/or
      gastroenterological interventions 24 hours a day. Most important is the personal
      motivation of the doctors and nurses in successfully supporting such a programme.
      So far the prospective implication on health care or medical education cannot be
      finally anticipated. The different independent factors of medical quality
      concerning pancreatic surgery have still to be identified and should reasonably
      influence any governmental or institutional regulations.

PMID- 19382050
TI  - [Diagnostic and therapeutic procedures in actinomycosis of the liver--a case
      report].
AB  - Actinomycosis is a rare disease. Clinical symptoms and diagnostic imaging results
      need to be differentiated from those of malignancies and abscesses. We report the
      case of a 51-year-old woman who presented with nocturnal sweating, weight loss,
      fever, and abdominal pains. Ultrasound and MRI showed a mass in the liver that
      was diagnosed as actinomycosis by fine needle -biopsy. Antibiotic therapy led to
      an initial de-crease of both the complaints and the size of the mass, but was
      followed by progressing inflammation and deterioration of the patient's general
      condition. Surgical intervention and resection of the liver lesion led to a near
      full recovery. Aetiology, symptoms, diagnostic measures and therapy are discussed
      in the context of the presented clinical case.

PMID- 19382051
TI  - [Aberrant gallstones--extraordinary complications of laparoscopic
      cholecystectomy].
AB  - About 0.2 % of patients undergoing laparoscopic cholecystetomy will suffer from
      complications caused by lost gallstones. Diagnostic and therapeutic measures are
      correlated to the symptoms. At different locations, abscesses can arise, which
      can be treated by direct access through the -abdominal wall, laparotomy or
      laparoscopy. Two cases are presented with the especially grave sequels of
      subphrenic abscess, infiltration of the thoracic wall, and pleural empyema, which
      -respectively needed several successive operations -after ten years. In
      laparoscopic cholecystectomy, all detected stones should be removed. In the case
      of a failure, conversion to laparotomy is not essential. The loss of stones has
      to be formally -documented, the patient and family doctor are to be informed.

PMID- 19382052
TI  - [Ectopic pancreatic tissue within a mediastinal cyst--a rare clinical
      manifestation].
AB  - BACKGROUND: We describe the case of a patient aged 25 years showing the rare
      finding of a mediastinal tumour containing ectopic pancreatic -tissue (maximum
      diameter of 15 cm). At admission, the patient presented with symptoms comparable
      to those of pneumonia. A computed tomographic scan of the thorax confirmed an 
      extensive mediastinal mass. A transthoracic puncture aspiration followed by a
      cytological examination failed to provide information of diagnostical relevance.
      OPERATION: To resect the mass and its adjacent tissue completely, a
      posterolateral thoracotomy on the left side was performed. The histopathological
      examination revealed exo- and endocrinic pancreatic tissue and a pancreatic
      pseudocyst with-out a thoracopancreatic fistula. DISCUSSION: The incidence of
      mediastinal cysts containing pancreatic tissue seems to be extremely low. Above
      all, our case is the only one presenting clinical symptoms of a lobar pneumonia.
      In consideration of the current literature, we give a description of histological
      pattern, the possible pathogenesis and classification. CONCLUSION: Surgical
      therapy provides the chance for tumour removal. It provides an excellent outcome
      when performed completely.

PMID- 19382053
TI  - [Carcinoma of the pancreas at the site of an intraductal papillary mucinous
      neoplasia].
AB  - Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are
      intraductally located, mucin-producing cystic neoplasms of the pancreas with a
      malignant potential. We report about a 54-year-old female who underwent segmental
      resection of the pancreas for non-invasive IPMN. The surgical margins were tumour
      negative. Three years later a highly suspicious tumour of the pancreatic tail was
      detected during routine follow-up. Resection of the pancreatic tail was
      performed. The histological analysis revealed an adenocarcinoma. This case
      suggests the development of a pancreatic carcinoma from a non-invasive IPMN and
      raises the question about the extent of surgery of non-invasive IPMNs of the
      pancreas.

PMID- 19382054
TI  - [Acute inguinal swelling--unusual presentation of postoperative necrotising
      pancreatitis].
AB  - Necrotising pancreatitis presenting as an acute inguinal swelling is an extremely
      rare condition. We report on a 61-year-old male who underwent explorative
      laparotomy for pancreatic tumour. Intraoperatively, the diagnosis of a locally
      advanced carcinoma of the head of the pancreas was confirmed histologically.
      During the postoperative course, the patient developed an acute inguinal
      swelling, which was suspected to be an incarcerated hernia. Intraoperatively,
      exploration of both abdomen and inguinal canal revealed an acute necrotising
      pancreatitis. This case is, to the best of our knowledge, the first case report
      on a postoperative necrotising pancreatitis masquerading as an incarcerated
      inguinal hernia in an adult male, and the diagnostic problems are discussed.

PMID- 19382055
TI  - Neuromuscular fatigue after resistance training.
AB  - This study examined the effects of heavy resistance training on dynamic exercise
      induced fatigue task (5 x 10RM leg-press) after two loading protocols with the
      same relative intensity (%) (5 x 10RM(Rel)) and the same absolute load (kg) (5 x
      10RM(Abs)) as in pretraining in men (n=12). Maximal strength and muscle power,
      surface EMG changes [amplitude and spectral indices of muscle fatigue], and
      metabolic responses (i.e.blood lactate and ammonia concentrations) were measured
      before and after exercise. After training, when the relative intensity of the
      fatiguing dynamic protocol was kept the same, the magnitude of exercise-induced
      loss in maximal strength was greater than that observed before training. The peak
      power lost after 5 x 10RM(Rel) (58-62%, pre-post training) was greater than the
      corresponding exercise-induced decline observed in isometric strength (12-17%).
      Similar neural adjustments, but higher accumulated fatigue and metabolic demand
      were observed after 5 x 10RM(Rel). This study therefore supports the notion that
      similar changes are observable in the EMG signal pre- and post-training at
      fatigue when exercising with the same relative load. However, after training the
      muscle is relatively able to work more and accumulate more metabolites before
      task failure. This result may indicate that rate of fatigue development (i.e.
      power and MVC) was faster and more profound after training despite using the same
      relative intensity.

PMID- 19382056
TI  - Interrupted resistance training and BMD in growing rats.
AB  - A resistance training program, where the exercise was uninterrupted (UT, i.e.
      continuous repetitions) was compared against another resistance training program
      where the exercise was interrupted (IT, i.e. 2 exercise sessions during a
      training day) for enhancing bone modeling and bone mineral density (BMD) in
      maturating animals. The total volume of work performed between the two resistance
      training programs was equivalent by design. Young male rats (approximately 8
      weeks old) were randomly divided into Control (Con, n=8), UT (n=8) and IT (n=7)
      resistance trained groups. The UT and IT groups were conditioned to climb a
      vertical ladder with weights appended to their tail 3 days/week for 6 weeks.
      After the 6 week training regimen (Mean+/-SD), tibial BMD (assessed via DXA) was
      significantly greater for UT (0.237+/-0.008 g/cm(2)) and IT (0.238+/-0.005
      g/cm(2)) compared to Con (0.223+/-0.004 g/cm(2)). Further, serum osteocalcin (OC)
      was significantly greater for UT (45.65+/-2.83 ng/ml) and IT (46.33+/-4.60 ng/ml)
      compared to Con (37.86+/-4.04 ng/ml). There was no significant difference in BMD
      or serum OC between UT and IT groups. The results indicate that both resistance
      training programs were equally effective in elevating BMD in growing animals.

PMID- 19382057
TI  - MMG-EMG cross spectrum and muscle fiber type.
AB  - The purpose of this study was to investigate fiber type-related differences in
      the patterns of responses for mechanomyographic-electromyographic (MMG-EMG) cross
      spectrum mean power frequency (MPF) in resistance-trained and aerobically-trained
      subjects during a fatiguing muscle action. Five resistance-trained and five
      aerobically-trained men performed a 45-s isometric muscle action of the dominant
      leg extensors at 50% MVC while MMG and EMG signals were recorded simultaneously
      from the vastus lateralis muscle. In addition, a biopsy was taken to determine
      the myosin heavy chain (MHC) isoform content of the vastus lateralis. The
      resistance-trained and aerobically-trained subjects demonstrated similar patterns
      of responses for MMG-EMG cross spectrum MPF during the sustained muscle action.
      The vastus lateralis of the resistance-trained subjects demonstrated primarily
      Type II MHC isoform expression, indicative of fast-twitch muscle fibers, while
      that of the aerobically-trained subjects was composed mostly of Type I MHC
      isoform expression, indicative of slow-twitch fibers. Thus, the differences in
      fiber type characteristics were not manifested in the patterns of responses for
      MMG-EMG cross spectrum MPF.

PMID- 19382058
TI  - Problems of the use of pseudoephedrine by athletes.
AB  - Pseudoephedrine (PSE) as a sympathomimetic is an ingredient of many proprietary
      medicines which are available on the medical market over the counter (OTC drugs).
      It can be converted to cathine (CATH, norpseudoephedrine) inside the body. Until
      the end of 2003, PSE had been a banned substance in sport in case its urinary
      concentration was greater than 25 mircog/ml. Then the World Anti-Doping Agency
      (WADA) removed PSE from the prohibited list. Prior to 2004 CATH was a forbidden
      substance and it is still one. CATH is included on the WADA prohibited list in
      the group of stimulants. The results of a doping control concerning PSE conducted
      in the Department of Anti-Doping Research of Institute of Sport in Warsaw in the
      years 2001-2003 and 2004-2007 have been compared. Moreover, several dozen of
      urine samples collected from the patients taking OTC drugs with PSE have been
      analysed. In these samples the concentration of PSE and CATH has been estimated.
      The results of this study have shown that athletes were using PSE frequently and
      in high doses between 2004 and 2007 when this substance was permitted by WADA. It
      is possible that athletes can obtain a positive result of doping control with
      CATH after the use of PSE.

PMID- 19382059
TI  - Metabolome analysis of Ephedra plants with different contents of ephedrine
      alkaloids by using UPLC-Q-TOF-MS.
AB  - Metabolome analysis of four varieties of Ephedra plants, which contain different
      amounts of ephedrine alkaloids, was demonstrated in this study. The metabolites
      were comprehensively analyzed by using ultra performance liquid chromatography
      (UPLC) coupled with quadrupole time-of-flight mass spectrometry (Q-TOF-MS) and
      the ephedrine alkaloids were also profiled. Subsequently, multivariate analyses
      of principal component analysis (PCA) and batch-learning self-organizing mapping
      (BL-SOM) analysis were applied to the raw data of the total ion chromatogram
      (TIC). PCA was performed to visualize the fingerprints characteristic for each
      Ephedra variant and the independent metabolome clusters were formed. The
      metabolite fingerprints were also visualized by BL-SOM analysis and were
      displayed as a lattice of colored individual cells which was characteristic for
      each Ephedra variant. BL-SOM analysis was also used for identification of
      chemical marker peaks because the information assigned to a cell represented
      either increases or decreases in peak intensities. Using this analysis, ephedrine
      alkaloids were successfully selected from the TICs as chemical markers for each
      Ephedra variant and this result suggested that BL-SOM analysis was an effective
      method for the selection of marker metabolites. We report our study here as a
      practical case of metabolomic study on medicinal resources.

PMID- 19382060
TI  - Three new alkaloids from Galanthus nivalis and Galanthus elwesii.
AB  - Phytochemical studies on Galanthus species resulted in the isolation of three new
      compounds: 3,3'-O-(3',3''-dihydroxybutanoyl)hamayne and 11,3'-O-(3',3''
      dihydroxybutanoyl)hamayne from G. nivalis and 2-O-(3'-hydroxybutanoyl)lycorine
      from G. elwesii. Additionally, 3,11-O-(3',3''-dihydroxybutanoyl)hamayne, 3,11,3'
      O-(3',3'',3'''-trihydroxybutanoyl)hamayne, 8-O-demethylvasconine, tazettine,
      epimacronine, and ismine from G. nivalis; 2-O-(3'-acetoxybutanoyl)lycorine and
      incartine from G. elwesii; and hamayne, 11-O-(3'-hydroxybutanoyl)hamayne and
      lycorine from both species were isolated. Their structures were determined by EI
      MS, HR-MS, CD, and 1D and 2D NMR (COSY, NOESY, HMQC, and HMBC) experiments.

PMID- 19382061
TI  - [Value of cardiovascular magnetic resonance imaging in the diagnosis of
      myocarditis].

PMID- 19382062
TI  - [President's letter].

PMID- 19382063
TI  - [Contrast-induced nephropathy: a contrast without a winner].

PMID- 19382064
TI  - [In search of the perfect biomarker for acute kidney injury: molecules of tubular
      origin again?].

PMID- 19382065
TI  - [Perfuse all or perfuse well? New prospects in kidney transplantation].

PMID- 19382066
TI  - [Endothelial rarefaction: bridge mechanism between acute kidney injury and
      chronic renal failure?].

PMID- 19382067
TI  - [Sodium thiosulfate: old weapons against new challenges].

PMID- 19382068
TI  - [Report from the 11th international symposium on urolithiasis].

PMID- 19382069
TI  - [Graft or CVC? A prosthetic graft is the better choice].
AB  - For more than 30 years, research and industry have attempted to introduce into
      clinical practice solutions and products that could remedy the impossibility to
      use native veins. Vascular grafts of various types have been created that would
      approach the ideal characteristics as closely as possible with low antigenic
      power, high resistance to infections, low risk of thrombosis, and easy
      pierceability but high resistance to puncturing. For this purpose various
      materials, either totally synthetic such as PTFE, biological homologous or
      heterologous, or biosynthetic with mixed components have been created. In
      addition, different configurations to improve the hemodynamic outline of
      synthetic grafts have been studied: grafts of varying caliber, conical or
      equipped with cuffs, and various systems of wall reinforcement to increase the
      resistance to punctures. But each of these types favors one aspect over another:
      biological grafts show better compliance with the native vein but offer less
      resistance to punctures and ectatic processes; synthetic grafts, instead, tend to
      be more vulnerable to intimal hyperplasia at the venous anastomosis, which is the
      Achilles' heel of grafts. In recent years, the use of tunneled central venous
      catheters (CVCs) has grown exponentially. This has offered a new, important
      solution to the vascular access problem, but the extensive use of CVCs is not
      always justified. In comparison with grafts, CVCs have various disadvantages
      including insertion-related complications, possible malfunctioning, risk of
      infections and thrombosis, but above all a high risk of steno-occlusion of
      central veins. Also in this field, research and industry are offering more and
      more reliable and secure products. More resistant, flexible, tolerable and less
      thrombogenic materials are being used and various configurations which would
      offer the best performance with the least insertion-related risks have been
      introduced: double-lumen CVCs with input and output staggered in oval and
      circular sections, separate-lumen CVCs, split CVCs, and so on. Also the
      radiological and ultrasound techniques of insertion have improved, thereby
      reducing risks and disadvantages. The choice of graft system or CVC is often
      determined not by clinical factors but by the preference or experience of the
      operator, the presence of a vascular surgeon, or a radiological staff experienced
      in vascular accesses. The probability of steno-occlusion of central veins, which
      may occur as early as 2 weeks after the procedure, could affect any other
      ''traditional'' vascular access in the corresponding limb owing to the high risk
      of arm edema. In the surgical timing, the preparation of a graft access should
      therefore precede the placement of a CVC. The refinement of endovascular
      procedures has allowed to increase the secondary patency considerably, permitting
      excellent survival of graft accesses. Statistical studies performed on large
      samples of patients have reported a marked increase in the mortality connected to
      CVC access, not only as a result of infection. There are, however, according to
      my surgical experience, some conditions in which the use of the CVC is a
      priority, namely in patients with severe cardiopathy and reduced ejection
      fraction in whom volume overload caused by a graft access increases the risk of
      cardiac failure; in pediatric patients weighing less than 20 kg, in whom a graft
      vascular access could cause notable, even insuperable, difficulties of
      construction and management, as well as negative psychological implications for
      the small patient; in very elderly patients in poor clinical condition with a
      short life expectancy or suffering from cancer, in whom a CVC could be used also
      for the infusion of chemotherapeutic drugs; and in patients with peripheral
      arteriopathy in whom the alternative is a graft in a lower limb, because of the
      high risk of ischemia.

PMID- 19382070
TI  - [When native arteriovenous fistula is not possible: the permanent catheter is
      better].
AB  - Native arteriovenous fistula is still the vascular access of choice in
      hemodialysis. Other options are arteriovenous graft or, in patients in whom it is
      not possible to create a surgical vascular access, a permanent venous catheter.
      International guidelines on vascular access for hemodialysis recommend an
      increase in the percentage of arteriovenous fistulas compared to other types of
      vascular access. An analysis of the data relative to the distribution of the
      types of vascular access in different countries highlights the difficulty in
      following this recommendation: the only country to have increased the number of
      arteriovenous fistulas in recent years is the US, where the percentage of grafts
      has decreased while the use of permanent catheters has increased. In Italy and
      the rest of Europe, the number of fistulas has remained stable, there has been a
      constant reduction in the number of grafts and an increase in the percentage of
      permanent catheters. The reasons for this distribution of the types of vascular
      access are multifactorial and include the increased average age of patients,
      frequent late referrals, and increased incidence of diabetes mellitus,
      cardiovascular disease, obesity, etc. These factors have brought about technical
      difficulties for the creation of fistulas and grafts, leading to an increase in
      the number of catheters used. In relation to the evolution of the clinical
      characteristics of dialysis patients, the permanent catheter should no longer be
      considered a last-choice vascular access: in selected patients, it can be a
      better choice than a surgical fistula or graft.

PMID- 19382071
TI  - [When the native arterial-venous fistula cannot be performed: graft or catheter?
      A comment].
AB  - In Italy, the logistics for the creation of a vascular access are not well
      arranged. Numerous specialists are involved, mostly on a voluntary basis: they
      are those who ''know how to make the vascular access'', and have earned the title
      on the battlefield. When a native arteriovenous fistula, the gold standard,
      cannot be created, different solutions may prevail, depending on the local
      availability of specific skills. The use of vascular grafts for vascular access
      is not common in Italy. Grafts are mainly performed by vascular surgeons or, less
      frequently, by nephrologists with specific expertise in centers of excellence. By
      contrast, venous catheterization as an emergency access for dialysis is very
      common in Italian nephrology and dialysis centers. In optimal operating
      conditions, when both options are available and fistula creation and management
      are feasible, the choice of a graft fistula would be almost obligatory, although
      there are exceptions. Usually, the need urges the renal physician to favor
      compromise solutions: a compromise between physician and patient, between who
      performs the vascular access and who manages dialysis, between the patient's
      right to express a choice and acute disease that requires a quick solution and
      positive outcome. We need a revision (or revolution?) of vascular access creation
      and management that will lead to a choice between venous catheter or vascular
      graft that is balanced and useful for the patient.

PMID- 19382072
TI  - [The advent of biosimilars: new rules to guarantee patient safety].
AB  - Biosimilars are medicinal products proposed as copies of biotech drugs whose
      patents have expired. Their entry into the therapeutic armamentarium entails
      knowledge of the rules established in Europe relevant to their use in clinical
      practice. In September 2007, an Italian panel of experts comprising two
      nephrologists, a clinical immunologist, an oncohematologist, a pharmacologist,
      and a hospital pharmacist examined the main features of biotech drugs and the
      issues faced by the regulatory authorities in the definition of a specific
      approval pathway for biosimilars in Europe. The panel of experts agreed that it
      is important to inform the medical and scientific community that biosimilars are
      not exact copies of their reference products; therefore the rules governing their
      clinical use are not the same as those established for biotech drugs in general.
      Patient safety should be the fundamental principle guiding therapeutic choices,
      and making these choices should be the prerogative of physicians.

PMID- 19382073
TI  - [Phosphatonins: novel insights and clinical perspectives].
AB  - Phosphate plays a vital role in several biological processes including energy and
      nucleic acid metabolism, cell signaling and bone mineralization. Several
      endocrine factors coordinately act on the intestine, kidney and bone to maintain
      their physiological homeostasis. A number of peptides, collectively known as
      phosphatonins, have recently been identified as regulators of phosphate
      metabolism in physiological and pathological conditions. These factors-
      fibroblast growth factors (FGF) 23 and 7, secreted frizzled related protein 4
      (sFRP-4), and matrix extracellular phosphoglycoprotein (MEPE)--primarily regulate
      tubular phosphate reabsorption by acting on the transmembrane expression of SLC34
      sodium-phosphate cotransporters. FGF- 23, FGF-7 and sFRP-4 also inhibit the
      biosynthesis of 1,25(OH)2D3, leading to decreased intestinal phosphate
      absorption. In this review, we discuss the biological properties of these
      peptides, their physiological roles, and the alterations in their concentrations
      in various hypophosphatemic and hyperphosphatemic clinical disorders.

PMID- 19382074
TI  - [Atheroembolic renal disease].
AB  - Atheroembolic renal disease can be defined as renal failure due to occlusion of
      the renal arterioles by cholesterol crystal emboli usually dislodged from
      ulcerated atherosclerotic plaques of the aorta. Atheroembolic renal disease is
      part of multisystem disease, since the embolization usually involves other organ
      systems such as the gastrointestinal system, central nervous system, and lower
      extremities. The kidney is frequently involved because of the proximity of the
      renal arteries to the abdominal aorta, where erosion of atheromatous plaques is
      most likely to occur. Embolization may occur spontaneously or after angiographic
      procedures, vascular surgery, and anticoagulation. In the last decade,
      atheroembolic renal disease has become a recognizable cause of renal disease. An
      ante-mortem diagnosis of the disease is possible in a significant proportion of
      cases as long as the level of diagnostic suspicion is high. The disease can
      severely affect kidney and patient survival. Although no specific treatment has
      been proven efficacious, use of statins may be justifiable and such therapy would
      be a reasonable choice for future treatment trials.

PMID- 19382075
TI  - [Kidney retransplantation: indications and limits].
AB  - Whether or not to consider a uremic patient for retransplantation remains a
      matter of debate. Donor shortage and putative poor outcomes are the main cons,
      improved results in the last decade and a better survival (HR 0.50) with
      retransplantation than dialysis stand as pros. The percentage of patients
      waitlisted for retransplantation or already having been retransplanted is
      increasing (up to 20-30%) and the absolute contraindications are limited to rare
      conditions (loss of previous transplant due to anti-glomerular basement
      antibodies in Alport's syndrome, early recurrence of GNF or hemolytic uremic
      syndrome). When retransplantation is considered, however, careful screening for
      risk factors is mandatory, whether they are related to the previous graft or to
      the recipient's clinical features or the donor's demographics and immunological
      status. In the last decade the clinical outcomes of retransplantation have
      significantly improved. No difference in patient survival at the fifth year has
      been reported between first, second and third grafts. The kidney survival at the
      same interval is above 70% for the second graft and 65% for the third graft.
      Nephrectomy of a previous graft is not necessary if not for clinical reasons. As
      far as the maximum number of retransplants is concerned, most transplant centers
      (69%) set no clear-cut limit. In conclusion, also taking into account that many
      patients after graft failure ask for readmission to the waiting list (75% in our
      experience), we think the retransplantation option should always be evaluated.

PMID- 19382076
TI  - [Malnutrition in patients on chronic hemodialysis: prevalence, pathogenesis, and
      treatment].
AB  - Malnutrition is common in patients on hemodialysis and is a strong predicor of
      morbidity and mortality. Much progress has been made in recent years in
      identifying the causes and pathogenesis of malnutrition in hemodialysis patients
      as well as in recognizing the link between malnutrition and morbidity and
      mortality. Nevertheless, there is no consensus concerning its management.
      Conventional interventions such as nutritional counseling, oral nutritional
      supplements and intradialytic parenteral nutrition and novel preventive and
      therapeutic strategies such as appetite stimulants, growth hormone, androgenic
      anabolic steroids, and antiinflammatory drugs have been tested with contradictory
      and inconclusive results. Malnutrition still remains an important challenge for
      the nephrologist in the third millennium.

PMID- 19382077
TI  - [Peritoneal dialysis in cirrhotic patients].
AB  - Renal failure and the need for dialysis worsen the prognosis of patients with
      combined liver and kidney disease. The choice of an appropriate dialysis
      technique should improve the life expectancy of these patients. Hypotension,
      impaired defence against infections, electrolyte and acid-base imbalance, severe
      protein and caloric malnutrition, hyperammonemia, hyperbilirubinemia, and
      inadequate response to diuretics present a number of clinical problems in
      patients with liver insufficiency. Liver failure is therefore considered an
      important risk factor for any type of dialysis. Theoretically, both hemodialysis
      and peritoneal dialysis may cause specific problems in these patients.
      Hemodialysis has an increased cost/benefit ratio in cirrhotic patients. The
      administration of heparin during dialysis might worsen blood coagulation, ascites
      is not controlled by hemodialysis, and frequent paracentesis may be necessary.
      The efficiency of hemodialysis in removing certain toxic substances accumulating
      in liver failure is still unclear. Peritoneal dialysis does not require
      anticoagulation, helps maintain residual renal function, allows continuous
      removal of a fixed amount of ascitic fluid, does not cause acute hemodynamic
      changes, clears some of the toxic metabolites accumulated by liver failure, and
      is less expensive. Finally, peritoneal dialysis is associated with continuous
      absorption of glucose through the mesenteric capillaries into the mesenteric and
      liver blood flow, thus improving caloric malnutrition. During the first months of
      peritoneal dialysis, cirrhotic patients lose about 10 g of protein in the
      peritoneal dialysate but this loss tends to decrease with time. All the available
      data seem to indicate that in cirrhotic patients on peritoneal dialysis the
      majority of complications are consequent upon liver disease, which is also the
      most important cause of death. The outcome of peritoneal dialysis is not affected
      by cirrhosis and is similar to that observed in noncirrhotic patients. All the
      evidence reported in the literature seems to indicate that in cirrhotic patients
      peritoneal dialysis is an adequate treatment of uremia.

PMID- 19382078
TI  - [Guidelines compared: a new series].

PMID- 19382079
TI  - [Guidelines for management of hypertension: why doesn't evidence lead to
      unanimity?].
AB  - Guidelines are systematically developed statements to assist practitioner and
      patient decisions, and are being used to describe care based on scientific
      evidence. However, presence of multiple guidelines on the same subject does not
      help physicians make the best decision about healthcare. In this paper we
      examined the more recent guidelines (GL) for the management of arterial
      hypertension: World Health Organization-International Society of Hypertension
      (WHO-ISH) GL, European Society of Hypertension-European Society of Cardiology
      (ESH-ESC) GL, British Hypertension Society (BHS-IV) GL, and the report of Joint
      National Committee (JNC-7) from USA. Some differences emerged on the definition
      of hypertension, the blood pressure targets and the thresholds for treatment, the
      quantification of cardiovascular risk, the choice of initial drugs. These
      differences are likely to be based on divergent opinions about the relationship
      between hypertension and global cardiovascular risk (CVR). In the JNC-7 report,
      hypertension is thought to be the mainstay of CVR, hence BP treatment is to be
      started, taking into account the entity of blood pressure values and apart from
      other risk factors (with the exception of diabetes and renal insufficiency). The
      other GL, particularly BHS-IV GL, establish the thresholds for the start of
      treatment mainly taking into account the global CVR. Actually, BHS-IV GL do not
      recommend the start of pharmacological treatment in mild hypertension, provided
      that the global CVR was lower than 20% in ten years. Moreover, the difference in
      definition of hypertension, BP targets, choice of starting drug, is likely to
      spring from this different view on hypertensionglobal cardiovascular risk
      relationship.

PMID- 19382080
TI  - [Steno-obstructions of haemodialytic FAV: new aspects of endovascular
      treatments].
AB  - Angioplasty is the usual method for the treatment of stenosis of arteriovenous
      fistulas for hemodialysis, along with fibrinolysis and thrombus aspiration. We
      evaluated the efficacy and safety of interventional radiology procedures in the
      treatment of stenosis or occlusion of arteriovenous fistulas. One hundred
      thirteen patients suffering from malfunction of arteriovenous fistulas underwent
      interventional radiological procedures (140 treatments). In all patients color
      Doppler was performed beforehand. Stenosis at the site of the fistula was found
      in all patients and was treated with percutaneous transluminal angioplasty (PTA);
      stenosis at the anastomosis site was found in 63 cases and was treated by
      angioplasty with a microcatheter. In 40 patients suffering from recent thrombotic
      occlusion, locoregional thrombolysis and PTA were necessary. Technical and
      clinical success was achieved in 107 patients (94.6%); in 1 of 6 unsuccessful
      treatments the procedure had to be interrupted due to the rupture of a vein.
      Follow-up exams demonstrated primary patency in 92.5%, 71.9% and 49.5% of
      patients at 6 months, 1 year and 2 years, respectively. In 19 patients (17.7%)
      hemodynamically significant restenosis was observed, which was treated with
      multiple PTAs (27 treatments, only 1 of which with a negative outcome), resulting
      in a 94.2% success rate; only 1 patient had to undergo a fourth PTA. The overall
      patency rate was 95%, 87.2%, 62.3% at 6 months, 1 year and 2 years, respectively.
      In our experience immediate success and excellent patency rates were observed,
      which persisted in the medium and long term. PTA, with thrombolysis and
      thromboaspiration, is the treatment of choice in cases of malfunctioning
      arteriovenous fistulas. PTA should always be attempted before making a new
      surgical access in order to preserve the vascular tree.

PMID- 19382081
TI  - [Why does a patient on hemodialysis have radiopaque material in his abdomen?].
AB  - Lanthanum is a third-generation, non-calcium and non-aluminium-based phosphate
      binder indicated for the treatment of hyperphosphatemia in stage 5 chronic kidney
      disease. The drug is well tolerated, with gastrointestinal complications as its
      main side effect. Recently, some case reports have described the typical X-ray
      features of this compound. We report another case of the radiopaque appearance of
      lanthanum carbonate, which underlines that clinicians need to be aware that its
      ingestion may cause opacifications in the colon.

PMID- 19382083
TI  - [Which nephrologist, today?].

PMID- 19382082
TI  - [The classics of Italian nephrology: ''Hormones in renal physiology and renal
      pathology'' by Silvano Lamperi (1922-2008) e Rodolfo Cheli (1928-1997)].
AB  - This monograph, published in 1955, describes the effects that cortisone,
      desoxycorticosterone, adrenocorticotropic hormone, growth hormone, and
      testosterone have on renal function, renal metabolism and renal enzymatic
      activity. The two main chapters of the book describe the experimental results
      obtained by the authors with the administration of the above-mentioned hormones
      to rats in terms of renal morphology and function both in basal conditions and
      after the injection of nephroptoxic substances. Interestingly, the effects on
      function were evaluated by the measurement of the consumption of oxygen by kidney
      sections incubated with hormones in different experimental conditions. The
      results demonstrated that both cortisone and adrenocorticosterone could have a
      protective effect on kidney damage, which could be used for clinical purposes.
      Today, the monograph by Lamperi and Cheli is interesting because it shows that
      advanced experimental research was carried out in Italy in the early 1950s.
      Moreover, it represents an early attempt to the application of experimental
      results to the clinic.

PMID- 19382084
TI  - [The medical acrobat (the new and ever increasing difficulties of the healthcare
      profession)].

PMID- 19382085
TI  - [Foreword. Prevention in nephrology, dialysis and kidney transplantation. The
      Fifth Convention, Mantova, May 23-24, 2008 ].

PMID- 19382086
TI  - [Proposals for the prevention of kidney disease in Italy by the Italian Society
      of Nephrology (SIN)].
AB  - Although national epidemiological data on the prevalence of chronic kidney
      disease in Italy are lacking, local and regional studies report that over 6% of
      the general population live with an eGFR <60 mL/min/1.73 m2 of body surface. In
      2007, the Italian Society of Nephrology (SIN) pointed out the main routes for the
      widespread recognition of the problem, involving the local agencies (ASLs) of the
      National Health Service in close collaboration with general practitioners and
      nephrologists, to ensure a wide range of information and continuous education of
      the general population on this issue. Special attention should be paid to
      financial and human resources, the shortage of nephrologists, and the role of the
      various stakeholders with the aim to counteract the progressive increase of CKD
      in the Italian population.

PMID- 19382087
TI  - [Reliability of administrative databases in epidemiological research: the example
      of end-stage renal disease requiring renal replacement therapy in patients with
      diabetes].
AB  - Health and administrative databases are widely used in epidemiology, mostly in
      studies of chronic diseases, but biases may undermine the external validity of
      the results. In nephrology, the use of these data sources is in its early days
      and needs to be validated. The aim of this study was to compare the data on the
      incidence of ESRD and death in a cohort of patients with type 2 diabetes (DM2)
      obtained from administrative databases with the results of a traditional, well
      performed cohort study. The study was conducted in the Health District of Venice
      (Italy) on a cohort of 18,416 DM2 patients on hypoglycemic drug therapy enrolled
      from 1 January 1998 to 31 December 2002 from administrative databases.Comorbid
      conditions were recorded from hospital discharge records, the database of death
      certificates was used to identify patients who died within 31 December 2004, and
      the database of the Dialysis and Transplantation Registry of the Veneto Region
      served to identify patients who started renal replacement therapy within 31
      December 2004. Record linkage was performed using the unique personal
      identification codes (fiscal number) of Italian citizens. The cumulative
      incidence of ESRD was estimated using Gray's method for competing risks. The
      mortality rate was 50.95 per 1000 person-years, the ESRD incidence was 0.68 per
      1000 person-years, with a relative risk of 2.62 with respect to all other causes
      of ESRD. The crude cumulative incidence of death was 22% and that of ESRD 0.33%
      at the end of follow-up. The results were similar to those obtained in
      traditional cohort studies. The results of our study prove the external validity
      of the administrative database approach in epidemiological studies in nephrology.

PMID- 19382088
TI  - [Mortality triplicates in acute myocardial infarction patients affected by
      chronic renal failure].
AB  - In order to calculate the cardiovascular risk in patients with chronic renal
      failure (CRF), we retrospectively analyzed 1482 acute myocardial infarctions
      (AMIs) treated in the ICU at C. Poma General Hospital, Mantua, Italy, from 1
      December 2004 to 31 July 2007. Of these patients, 133 suffered from CRF at
      hospital admission (eGFR <40 mL/min/1.73 m2 body surface and/or serum creatinine
      >2 mg/dL). During hospitalization for AMI, the CRF-affected patients showed a 2.7
      times higher relative risk of mortality than patients without CRF (Yates chi
      square 14.46; p = 0.0001432). The evaluated comorbidities (hypertension, type 2
      diabetes, supra-aortic vascular stenosis >70%, previous PTCA, COPD, previous AMI,
      previous coronary artery bypass and chronic obliterative peripheral arteriopathy)
      increased the relative risk of death 1.2- to 3.76-fold in those affected. In
      accord with recent evidence in the international literature, our results point to
      the importance of early assessment of CRF for the prognosis of patients with AMI.

PMID- 19382089
TI  - [Do convective treatments significantly reduce morbidity and mortality?].
AB  - Standard hemodialysis is a far from ideal treatment for uremia since the
      morbidity and mortality of patients on hemodialysis are still significantly
      higher than those of non-hemodialyzed subjects with similar demographic
      characteristics. Because it has been suggested that the cause could lie in the
      inadequate removal of ''middle molecules'' by standard hemodialyis, two
      alternative treatments have been proposed: high-efficiency hemodialyis and high
      flux hemodialyis. The 2002 results of the HEMO study showed that both these
      treatments are associated with a non-significant reduction in the relative risk
      of death (4% and 8%, respectively). The MPO study, which - unlike the HEMO study 
      enrolled only incident cases and not did not allow reuse of dialyzers, evaluated
      the mortality rate with high-flux and low-flux hemodialysis in a sicker
      population, i.e., patients with hypoalbuminemia, and showed a significant
      reduction in the relative risk of death especially in patients with diabetes. In
      an attempt to define the clinical impact of hemodiafiltration, some of the
      efficacy data from clinical studies are reviewed in light of a number of factors
      that may be related to the high mortality among hemodialysis patients. The
      current state of affairs suggests it is reasonable to prefer high-flux
      hemodialysis in sicker patients, especially diabetics. Moreover, the use of
      ultrapure dialysis fluid is recommended to reduce chronic inflammation and its
      consequences.

PMID- 19382090
TI  - [Pathogenesis and treatment of vascular calcification in CKD].
AB  - Increased vascular calcification is a major cause of cardiovascular events in
      patients with chronic kidney disease (CKD). It is the result of an active
      ossification process counteracted by ''bone'' proteins such as osteopontin,
      alkaline phosphatase, osteoprotegerin, and osteocalcin. Chronic kidney disease -
      mineral and bone disorder (CKD-MBD) is a systemic disorder of mineral and bone
      metabolism that occurs in CKD. In addition to abnormalities in the serum calcium
      and phosphate profile, CKD-MBD is characterized by abnormalities of bone
      turnover, mineralization, volume and growth as well as vascular calcification.
      Considering that the presence and extent of vascular calcification in CKD portend
      a poor prognosis, many efforts have been made to shed light on this complicated
      phenomenon to prevent vascular calcium deposition and its progression. Indeed,
      careful control of calcium load, serum phosphate and parathyroid hormone along
      with the use of calcium-free phosphate binders and vitamin D receptor activators
      represent a new therapeutic armamentarium to improve quality of life and reduce
      mortality in CKD.

PMID- 19382091
TI  - [Prevention and therapy of critical ischemia in hemodialyzed patients].
AB  - The cardiovascular disease is largely increased in chronic renal failure and the
      patients have a 10-20 times higher mortality respect normal population. Besides
      habitual risk-factors they add the mineral metabolism alterations,
      iperomocisteine and chronical vessel flogosis. In these patients the vascular
      disease is often lately diagnosed, but early diagnosis would be extremely
      important to establish appropriate pharmacologic or surgical treatment (PTA or by
      pass). The basic diagnostic methods are still digital angiography, angio-NMR or
      angio-CT. In our experience appears that dialysed patients present high total
      mortality and re-vascolarization (particularly for peripheral occlusive disease)
      gives less guarantee of success. During last years endovascular surgery
      procedures extremely improved short-term prognosis for these patients. When there
      is no space for the re-vascolarization and the situation is strongly compromised
      by the presence of extended gangrene or infected lesion, amputation is still
      indicated and can be considered the only possible solution.

PMID- 19382092
TI  - [Blood-borne infections in hemodialysis: facts and opinions].
AB  - The epidemiological impact of blood-borne infections (HCV, HBV and HIV) in
      dialysis is a major concern. In the past two decades the implementation of
      specific recommendations for prevention has been associated with a sharp
      reduction of the HBV and HCV incidence in this setting. Moreover, in recent years
      new therapeutic agents against these viruses were introduced, resulting in a
      marked improvement in clinical outcomes in subjects with normal kidney function.
      A collaborative effort between nephrologists and infectious disease specialists
      should be made to extend this improvement to chronic kidney disease patients.

PMID- 19382093
TI  - [Preventing and reducing comorbidity in candidates for kidney transplantation for
      the improvement of post-operative results].
AB  - The correct and constant management of transplant waiting lists is necessary for
      the optimal utilization of the limited number of organs available for
      transplantation. The guidelines regarding placement on transplant waiting lists
      (absolute and relative contraindications) are well documented, even though they
      are in constant development. The criteria for the monitoring of patients on
      waiting lists, however, are not so well defined; this aspect is subject to
      careful evaluation on account of the widening of the criteria for transplantation
      suitability, the increase in the average age of patients, a rise in the number of
      enrolments and, as a result, prolonged waiting time (in Italy, the average time
      spent on a waiting list is 37 months). During the waiting period, a greater risk
      of clinically significant comorbidities and mortality, above all from
      cardiovascular events, has been noted (the annual mortality is 5-7% in the US,
      1.3% in Italy). An in-depth clinical and instrumental study of patients with
      chronic renal failure is necessary when screening eligible candidates for
      transplant programs, individualizing therapeutic strategies, and identifying
      patients for whom the risks outweigh the potential benefits. Clinical and
      instrumental monitoring, as well as adequate treatment of comorbidities during
      the waiting period, can help improve the post-transplant outcome. This work
      examines the study algorithms and monitoring procedures for patients on kidney
      transplant waiting lists.

PMID- 19382094
TI  - [Cytomegalovirus and BK polyomavirus infection after renal transplantation].
AB  - Cytomegalovirus (CMV) and BK polyomavirus (BKV) infections have been described in
      a high percentage of renal transplant patients and are known to cause various
      complications in renal transplantation. They are closely related to
      immunosuppressive therapy and implicated in the progression of graft failure.
      This review focuses on the clinical aspects of CMV and BKV infection after renal
      transplantation, optimal monitoring, and recent preventive measures and
      interventions to improve graft function and recipient survival.

PMID- 19382095
TI  - [Regulatory T cells in kidney transplant recipients].
AB  - Immunosuppressive drugs are essential for the prevention of acute transplant
      rejection but some may not promote long-term tolerance. Tolerance to self
      antigens is ensured naturally by several mechanisms; one major mechanism depends
      on the activity of regulatory T lymphocytes (Treg), particularly CD4+CD25+ T
      cells. The transcription factor forkhead box protein 3 (Foxp3) has been
      identified as a molecular marker for Treg cells. The direct effects of
      immunosuppressive drugs on CD4+CD25+ cells are uncertain. In the clinical
      setting, basiliximab used in the induction phase of immunosuppression effectively
      reduced the number of acute rejection episodes. We studied the effects of the
      most widely used immunosuppressive induction regimens including cyclosporine,
      mycophenolate mofetil, steroids, and anti-CD25 monoclonal antibody (basiliximab)
      on the capacity to regulate human Treg in vivo. Twenty first cadaveric kidney
      transplant recipients (14 men, 6 women) were enrolled in the study. Blood samples
      were collected before kidney transplant and after one month. Blood sampling was
      done immediately before the administration of immunosuppressive therapy after an
      overnight fast. None of the transplant recipients presented laboratory or
      clinical signs of infection or acute rejection. The number and percentage of
      CD4+CD25+ and Foxp3+ T cells were determined by fluorescence activated cell
      sorter (FACS) analysis. Our results showed absence of both CD4+CD25+ and
      CD4+CD25+ Foxp3+ T cells one month after transplant. Peripheral CD4+CD25-Foxp3+ T
      cells significantly decreased after transplant but did not disappear. These
      preliminary data suggest that immunosuppressive induction therapy with
      basiliximab completely suppresses CD4+CD25+ regulatory cells and significantly
      reduces the total number of Foxp3+ lymphocytes.

PMID- 19382096
TI  - [Anti-HLA antibodies after bone graft and their impact on kidney transplant
      programs].
AB  - Immunological evaluation by panel reactive antibody (PRA) and determination of
      anti-HLA specificity is an important phase in the assessment of patients awaiting
      kidney transplant. The main causes of immunization are previous solid organ
      transplants, blood transfusions, and pregnancy; immunogenicity can also be
      triggered by vascularized tissue grafts. Immune induction by cryopreserved bone
      allografts is not yet fully understood. We report the case of a 19-year-old
      patient with osteosarcoma who underwent resection of the left proximal tibia with
      reconstruction using human bone in 1997 (donor typing: A3, A29 (19) - B44 (12),
      Bw4 - DR13 (6), DR7, DR52, DR53). The patient was subsequently placed on the
      waiting list for a cadaver donor kidney transplant because of chronic kidney
      failure caused by cisplatin toxicity. Pretransplant immunological screening using
      the CDC (complement dependent cytotoxicity) technique revealed a PRA of 63% and
      anti-A3 and anti-A68 antibodies. The presence of IgG antibody specificity against
      class I and class II donor antigens (specifically anti-A3, B44, DR7 antibodies)
      was highlighted using flow cytometry (Tepnel-Luminex). Further immunological
      studies using single HLA specificity analysis (LSA Class I - II - Tepnel-Luminex)
      detected direct antibodies against all donor antigen specificities. This is the
      first reported case of immune induction after a bone graft in a kidney transplant
      candidate. It underlines the importance of the availability of HLA typing data of
      all human allograft donors.

PMID- 19382097
TI  - [Expression of metanephric differentiation markers in human mesenchymal stem
      cells].
AB  - Stem cells are a potential source for the regeneration of many tissues, including
      damaged kidneys. The present study describes the adoption of hyaluronic- butyric
      acid monoesters (HB) to induce expression of nephrogenic genes by mesenchymal
      cells isolated from human placental membranes. HB at a concentration of 1 mg/mL
      induces chromatin opening and increases the expression of the observed markers
      (cadherin 11, CD24, RAR-alpha, stearoyl-CoA desaturase 2, 14-3-3 0, Ewing sarcoma
      homolog.). These results open new routes toward cell regeneration after kidney
      injury.

PMID- 19382098
TI  - [Mantova cell factory: a model for skin regeneration].
AB  - Chronic wounds, including venous and arteriosclerotic leg ulcers, diabetic foot
      ulcers, decubitus and trauma-induced wounds, represent a major problem in our
      society. Because the incidence of chronic wounds is high, the socioeconomic
      impact is considerable. The problem increases as the average age of the
      population increases and so the research into wound healing is continuously on
      the move. The aim of our research was to develop an autologous skin substitute
      and to verify its efficacy in closing chronic ulcers that do not respond to the
      currently available wound-healing treatments (topical therapy, antibiotics,
      surgical cleansing, external compression). Keratinocytes were obtained from the
      patients' foreskins. All medical procedures were undertaken with the approval of
      the ethics committee and with the patient's consent. In our survey we evaluated
      the possibility to grow autologous keratinocytes both with the ''feeder-layer''
      method and on a type I collagen substrate. Using the first method, we obtained a
      two-dimensional strip composed of a few layers of normally arranged
      keratinocytes; it was, however, very fragile and this may affect the efficacy in
      clinical use. When cells were grown on an appropriately treated type I collagen
      substrate, we obtained more layers of normally arranged keratinocytes which were
      also differentiated into basal, spinous, granular and keratin layers. In addition
      to keratinocyte reproduction, we obtained reproduction of melanocytes in the
      correct basal position. The new skin substitute provides a new treatment option
      for chronic wounds that are refractory to conventional therapies. Adequate
      cytohistological and immunohistochemical analysis to evaluate the cells' correct
      morphology and phenotype is important in this technique.

PMID- 19382099
TI  - 'A disease many people still feel uncomfortable talking about': Australian
      television coverage of colorectal cancer.
AB  - OBJECTIVE: To examine the coverage of colorectal cancer on Australian television
      news over a 3 year period commencing May 2005, and compare it with that given to
      other cancers. METHODS: News reports on colorectal cancer broadcast on Sydney's
      five free-to-air television channels between 3 May 2005 and 30 May 2008 were
      reviewed for statements by news actors. The frequency of coverage was compared
      with that for other cancers. RESULTS: Colorectal cancer news reports accounted
      for 4.1% (95% CI 2.9-5.1%) of all cancer news reports while the cancer represents
      13.5% of cancer incidence and 11.5% of cancer deaths. Compared to cancers
      receiving greater television news coverage, there was a near total absence of
      reports of celebrity diagnoses, and of representations by colorectal advocacy
      groups. A national colorectal screening programme received limited coverage.
      CONCLUSIONS: Media neglect of colorectal cancer may be an important factor in
      explaining low participation in the Australian colorectal screening programme.
      Those advocating for colorectal cancer screening face ingrained cultural
      challenges in gaining broad media coverage, but investment in efforts to generate
      news and commentary would appear to be overdue.

PMID- 19382100
TI  - Psychological distress and use of psychosocial support in familial adenomatous
      polyposis.
AB  - OBJECTIVE: Familial adenomatous polyposis (FAP) is characterized by multiple
      adenomas in the colorectum with a high risk to develop colorectal cancer. It is
      unclear whether individuals at risk of FAP experience distress due to this
      potentially life-threatening disease. This nationwide study assessed: (1) the
      prevalence of psychological distress; and (2) the need for and use of specialized
      professional psychosocial support. METHODS: In this cross-sectional study, all
      individuals from families at high risk for FAP registered at the Netherlands
      Foundation for the Detection of Hereditary Tumours were invited to complete a
      questionnaire assessing, among other issues, generalized, cancer-specific and FAP
      specific distress. RESULTS: In total, 525 individuals completed the
      questionnaire. Approximately 20% of the respondents had moderate to severe levels
      of FAP-specific distress. Levels of generalized distress were comparable to the
      general Dutch population. Significantly more individuals with a FAP diagnosis had
      frequent cancer worries than those at risk of FAP or non-carriers (p=0.02).
      Distress levels were more strongly associated with psychosocial variables (e.g.
      perceived cancer risk), than with sociodemographic or clinical variables. Up to
      43% of the variance in distress could be explained by all variables combined. Of
      those moderately to severely distressed, 26% had received specialized
      professional psychosocial support, while 30% of those did not receive the support
      they wanted. CONCLUSIONS: A substantial minority of individuals reported moderate
      to severe distress levels associated with FAP. However, only one-third of those
      received specialized professional psychosocial support. We recommend the use of a
      screening questionnaire to identify individuals in need of such support.

PMID- 19382101
TI  - Valuing difference: caregiving by mothers of children with disabilities.
AB  - Mothers who are caregivers of children with disabilities seek to have their
      children accepted and valued by others in society. This is supported by many
      reports of studies from different countries that involved mothers of children
      with disabilities, as well as through publications by disability advocates. In
      this paper, qualitative research data from interviews with seven mothers of
      children with disabilities were reanalysed using Bourdieu's theory of practice
      and van Manen's phenomenological methodology. The results showed that these
      mothers, who were caregivers of children with disabilities, valued their children
      despite ongoing challenges, and wanted others to do likewise. This study supports
      the importance of valuing difference in terms of the insights and understanding
      gained from those with disabilities and their caregivers. It would be difficult
      to replicate it exactly; its relevance lies in demonstrating that valuable
      insights can be gained from extending reflective practice to research that
      involves re-examining a study from a different theoretical perspective.

PMID- 19382102
TI  - Social interactions and smoking: evidence using multiple student cohorts,
      instrumental variables, and school fixed effects.
AB  - In this paper, I use a social interactions framework to detect whether individual
      smoking decisions are influenced by classmate smoking decisions. There are
      several large challenges in addressing this question, including the endogeneity
      of school (and thus classmates) through residential location choices, 'third
      factors' such as school-level unobservables that influence individual and
      classmate choices simultaneously, and the difficulty of the identification of
      parameters in empirical models of social interactions. In order to address these
      issues, I use an instrumental variables/fixed effects methodology that compares
      students in different grades within the same high school who face a different set
      of classmates and classmates' decisions. Preferred specifications suggest that
      increasing the proportion of classmates who smoke by 10% will increase the
      likelihood an individual smokes by approximately 3 percentage points. I compare
      these results with previous findings that are unable to use school fixed effects
      and/or use potentially invalid instruments and find that the current results
      suggest smaller social interactions in adolescent smoking decisions than some
      previous work.

PMID- 19382103
TI  - Switch from a dominant Th1-associated immune profile during the pre-diabetic
      phase in favour of a temporary increase of a Th3-associated and inflammatory
      immune profile at the onset of type 1 diabetes.
AB  - BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease dominated by loss of
      self-tolerance resulting in depletion of the beta-cells. This study aims to
      confirm previous observations of a dominant T-helper (Th)1-like profile during
      the period close to onset of disease. Further, to follow the immune response from
      onset to 2 years duration, the study focused on spontaneous as well as
      autoantigen-induced immune profile. METHODS: Peripheral blood mononuclear cells
      were collected 4 days and 1 and 2 years after diagnosis of T1D children, from
      healthy children carrying the human leukocyte antigen-risk genes and from high
      risk children (ICA > or = 20 IJDF units). Peripheral blood mononuclear cells were
      stimulated with glutamic acid decarboxylase (GAD(65)) and phytohaemagglutinin
      (PHA). Cytokines and chemokines were detected in cell-culture supernatants by
      protein microarray (naive T-cells; interleukin (IL)-7, Th1; interferon-gamma,
      tumour necrosis factor-beta, Th2; IL-5, Th3; transforming growth factor-beta, T
      regulatory cell type 1; IL-10 and inflammatory cytokines; tumour necrosis factor
      alpha, IL-6 and chemokines; monocyte chemoattractant protein-1, monokine
      upregulated by IFN-gamma) in relation to clinical outcome (C-peptide). RESULTS:
      High-risk children showed a dominant Th1-associated profile with high spontaneous
      and GAD(65)-induced secretion. The mitogen PHA instead induced a Th2-associated
      response exclusively in high-risk children. In contrast, newly diagnosed T1D
      children showed a pronounced Th3-associated cytokine profile as well as a burst
      of inflammatory cytokines and chemokines secreted both spontaneously and by
      GAD(65) and PHA stimulation. The immune response to GAD(65) and PHA, however,
      diminished with duration of disease. CONCLUSION: A dominant Th1-associated immune
      profile was observed during the pre-diabetic phase. This Th1 dominance, however,
      diminished in favour of a temporary increase in a Th3-associated and inflammatory
      immune profile at the onset of disease.

PMID- 19382104
TI  - Phytoglycoprotein (75 kDa) isolated from Cudrania tricuspidata Bureau inhibits
      expression of interleukin-4 in the presence of di (2-ethylhexyl) phthalate via
      modulation of p38 mitogen-activated protein kinase in primary-cultured mouse
      thymocytes.
AB  - The purpose of this study is to determine the inhibitory effect of a glycoprotein
      isolated from Cudrania tricuspidata Bureau (CTB glycoprotein) on di(2-ethylhexyl)
      phthalate (DEHP)-induced differentiation of T helper (Th) type 2 cells in primary
      cultured thymocytes. The results obtained from this study revealed that the CTB
      glycoprotein in the presence of DEHP produces an antioxidative activity against
      intracellular reactive oxygen species production in cells. In addition, the
      activities of p38 mitogen-activated protein kinase and GATA-binding protein 3
      were decreased by treatment with the CTB glycoprotein (100 microg ml(-1)). The
      CTB glycoprotein also has an inhibitory effect on the expressions of interleukin
      (IL)-4 and IL-10 induced by DEHP in thymocytes. Hence, we speculate that the CTB
      glycoprotein might be one component for preparation of health supplements for
      prevention of Th2 cell response-related immune diseases.

PMID- 19382105
TI  - Sample size for two-stage studies with maintenance therapy.
AB  - An adaptive treatment strategy (ATS) is defined as a sequence of treatments and
      intermediate responses. ATS' arise when chronic diseases such as cancer and
      depression are treated over time with various treatment alternatives depending on
      intermediate responses to earlier treatments. Clinical trials are often designed
      to compare ATSs based on appropriate designs such as sequential randomization
      designs. Although recent literature provides statistical methods for analyzing
      data from such trials, very few articles have focused on statistical power and
      sample size issues. This paper presents a sample size formula for comparing the
      survival probabilities under two treatment strategies sharing same initial, but
      different maintenance treatment. The formula is based on the large sample
      properties of inverse-probability-weighted estimator. Simulation study shows
      strong evidence that the proposed sample size formula guarantees desired power,
      regardless of the true distributions of survival times.

PMID- 19382106
TI  - Dynamic versus static models in cost-effectiveness analyses of anti-viral drug
      therapy to mitigate an influenza pandemic.
AB  - Conventional (static) models used in health economics implicitly assume that the
      probability of disease exposure is constant over time and unaffected by
      interventions. For transmissible infectious diseases this is not realistic and
      another class of models is required, so-called dynamic models. This study aims to
      examine the differences between one dynamic and one static model, estimating the
      effects of therapeutic treatment with antiviral (AV) drugs during an influenza
      pandemic in the Netherlands. Specifically, we focus on the sensitivity of the
      cost-effectiveness ratios to model choice, to the assumed drug coverage, and to
      the value of several epidemiological factors. Therapeutic use of AV-drugs is cost
      effective compared with non-intervention, irrespective of which model approach is
      chosen. The findings further show that: (1) the cost-effectiveness ratio
      according to the static model is insensitive to the size of a pandemic, whereas
      the ratio according to the dynamic model increases with the size of a pandemic;
      (2) according to the dynamic model, the cost per infection and the life-years
      gained per treatment are not constant but depend on the proportion of cases that
      are treated; and (3) the age-specific clinical attack rates affect the
      sensitivity of cost-effectiveness ratio to model choice.

PMID- 19382108
TI  - Optimizing the test power for a radiation retention model in the human body.
AB  - The model that describes the retention in lungs of radioisotope particles is
      studied in this paper, considering the situation of an accident in facilities
      that handle radioactive materials. Optimal times to make the bioassays are
      computed for D- and c-optimality, and efficiencies for the computed designs are
      provided and compared. Moreover, the test power is checked by means of
      simulations and replications. After that the inverse of the Fisher information
      matrix is compared to an estimation of the covariance matrix of the parameters.
      Finally, a study taking into consideration the randomness of the designs space is
      performed.

PMID- 19382109
TI  - Asymmetric spin-echo (ASE) spiral improves BOLD fMRI in inhomogeneous regions.
AB  - Functional MRI (fMRI) is of limited use in areas such as the orbitofrontal and
      inferior temporal lobes due to the presence of local susceptibility-induced field
      gradients (SFGs), which result in severe image artifacts. Several techniques have
      been developed to reduce these artifacts, the most common being the dual-echo
      spiral sequences (spiral-in/out and spiral-in/in). In this study, a new multiple
      spiral acquisition technique was developed, in which the later spiral
      acquisitions are acquired asymmetrically with the peak of a spin-echo causing
      increased R(2)-weighting but matched R(2)'-weighting. This sequence, called
      asymmetric spin-echo (ASE) spiral, has demonstrated significant improvements in
      minimizing the signal loss and increasing the image quality as well as optimal
      blood-oxygen-level-dependent (BOLD)-weighting. The ASE spiral is compared to
      conventional spiral-out using both signal-to-noise ratio (SNR) and whole brain
      fMRI activation volumes from a breath-hold task acquired at 4 Tesla. The ASE dual
      spiral has exhibited SNR increases of up to 300% in areas where strong SFGs are
      present. As a result, the ASE spiral is highly efficient for recovering lost
      activation in areas of SFGs, as demonstrated by a 16% increase in the total
      number of activated voxels over the whole brain. Post spin-echo ASE spiral images
      have decreasing SNR due to R(2) signal losses, however the increase in R(2)
      weighting leads to a higher percentage of signal changes producing ASE spiral
      images with equivalent contrast-to-noise ratio (CNR) for each echo. The use of
      this sequence allows for recovery of BOLD activation in areas of SFG without
      sacrificing the CNR over the whole brain.

PMID- 19382110
TI  - Psychological interventions with siblings of pediatric cancer patients: a
      systematic review.
AB  - OBJECTIVE: Siblings of pediatric cancer patients have been shown to be at risk
      for developing emotional, behavioral, and social problems. There is a need for
      psychological interventions in this population. Several researchers have
      previously documented and evaluated their interventions with siblings. This paper
      aimed at reviewing the existing reports of evaluated psychological interventions
      with siblings of pediatric cancer patients and at outlining future directions.
      METHODS: Research was conducted on several online bibliographic databases.
      Articles were selected on the basis of predefined criteria. If possible, effect
      sizes (ES) were calculated. RESULTS: Fourteen studies representing 11 different
      sibling interventions met criteria for inclusion. One individual intervention,
      three camps, and seven groups were found. Objectives of interventions
      concentrated mainly on enhancing siblings' coping and improving their medical
      knowledge. In terms of outcome measures, most of the studies focused on
      psychological adjustment variables. Findings showed significant improvements in
      siblings' depression symptomatology, medical knowledge, and health-related
      quality of life. Findings were inconsistent with regard to anxiety, behavioral
      problems, social adjustment, self-esteem, and posttraumatic stress symptoms.
      Depending on the outcome variables, small to large ES were found. Satisfaction
      with the intervention was high in both siblings and parents. CONCLUSION: There is
      tentative evidence that psychological interventions with siblings of childhood
      cancer patients can effectively reduce psychological maladjustment and improve
      medical knowledge about cancer. However, the number of studies is small, and
      several methodological shortcomings have to be noted. In future, more randomized
      controlled trials need to be conducted in larger samples to extend the evidence
      base.

PMID- 19382111
TI  - At-risk alcohol drinking in primary care patients aged 75 years and older.
AB  - BACKGROUND: Little is known about the prevalence and risk factors of alcohol
      problems among older people (especially those aged 75 years and more). The aims
      of this study were to report alcohol consumption patterns and to determine their
      association with socio-demographic variables and health characteristics. METHOD:
      3224 non-demented subjects aged 75 and over and attending general practitioners
      (GPs) (n = 138) in an urban area of Germany were studied by structured clinical
      interviews including detailed assessment of alcohol consumption patterns
      distinguishing between abstainers, moderate drinkers and at-risk drinkers (>20 g
      of alcohol for women and >30 g of alcohol for men). RESULTS: A high proportion
      (50.1%) of the sample were abstainers, 43.4% were moderate drinkers. The
      prevalence of at-risk alcohol consumption was 6.5% (95% CI 5.6-7.4). Rates were
      significantly higher for men (12.1%; 95% CI 10.2-14.0) compared to women (3.6%;
      95% CI 2.8-4.4). After full adjustment for confounding variables we found that
      compared to moderate drinking abstaining from alcohol was significantly
      associated with female gender, lower education, and mobility impairment. Compared
      to moderate drinking at-risk drinking was significantly higher among men,
      individuals with a liver disease, and current smokers. CONCLUSIONS: Multivariate
      analysis revealed that, apart from liver disease, at-risk drinking in a non
      demented population aged 75 and over was associated with relatively good physical
      and mental health. Nevertheless, public prevention measures should focus on at
      risk drinkers to make them aware of potential risks of high alcohol consumption
      in old age.

PMID- 19382112
TI  - Cancer patients' desire for psychological support: prevalence and implications
      for screening patients' psychological needs.
AB  - OBJECTIVES: To investigate cancer patients' desire for psychological support and
      to identify patients' sociodemographic, disease-related and psychological factors
      associated with this desire. METHODS: The study is part of a multicenter, cross
      sectional study assessing cancer patients' needs and desire for psychological
      support. Patients completed the Hospital Anxiety and Depression Scale, the Ways
      of Coping Checklist, the Cancer Rehabilitation Evaluation System and reported
      their desire for psychological support. RESULTS: Among the 381 included patients,
      women (26%) desired psychological support significantly more often than men (11%)
      (p<0.001). Patients' desire for psychological support was associated with being
      younger (OR=0.94; p<0.001 for women and OR=0.93; p=0.007 for men) and having a
      support-seeking coping (OR=1.10; p=0.010 for women and OR=1.36; p=0.003 for men).
      Other contextual factors such as difficulties encountered and treatment
      modalities were diversely associated with women and men's desire for
      psychological support. Neither women's, nor men's psychological distress was
      associated with their desire for psychological support. CONCLUSIONS: One female
      cancer patient out of four and one male cancer patient out of ten desire
      psychological support. Results emphasize the need to screen not only for cancer
      patients' distress but also for their desire for psychological support. This will
      allow implementing psychological interventions according to patients' needs and
      desire.

PMID- 19382113
TI  - MAOA gene polymorphisms and response to mirtazapine in major depression.
AB  - BACKGROUND: Polymorphisms in the monoamine oxidase A (MAOA) gene may influence
      treatment outcomes in major depression disorder (MDD). OBJECTIVE: To investigate
      the association of MAOA genetic polymorphisms and response to mirtazapine in
      patients with MDD. METHOD: Fifty-eight adult patients in Taiwan who met the
      Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)
      diagnostic criteria for MDD were given mirtazapine for 7 weeks and evaluated on
      days 0, 7, 14, 21, 49 using the 24-item Hamilton Rating Scale for Depression
      (HRSD). Remission was defined as a final HRSD <or= 10 and a 50% reduction in
      baseline HRSD score. Patients provided venous blood for DNA testing. The
      patients' response to mirtazapine treatment was compared between those who had
      the long-form polymorphism in the MAOA gene promoter and the short-form
      polymorphism. RESULT: The total HRSD scores after mirtazapine treatment were
      significantly lower than baseline (p < 0.001). There were 10 cases (38.5%) in
      short from and 6 (18.8%) in long from group touched the remission stage. Patients
      with the short-form group had a greater response to mirtazapine (p < 0.001) than
      those with the long-form polymorphism after controlling for age, sex, and
      apolipoprotein E genetic (APOE) polymorphism. CONCLUSION: The genetic
      polymorphisms in the MAOA promoter region may be associated with treatment
      response to mirtazapine.

PMID- 19382115
TI  - Evidence for pseudoknot formation of class I preQ1 riboswitch aptamers.
AB  - All in a knot. The smallest riboswitch forms a pseudoknot in solution. This is
      demonstrated for preQ(1) class I aptamers by mutational analysis in combination
      with (1)H NMR-based structure probing. How pseudoknot formation mediates the mRNA
      response through its expression platform is now open for investigation.

PMID- 19382116
TI  - Motives that cancer patients in oncological care have for consulting a
      psychologist--an empirical study.
AB  - OBJECTIVE: Most people with cancer are able to deal with the mental turmoil with
      support from ordinary health care, family and friends. However, by themselves or
      by attentive health-care workers some patients are referred to specialists within
      the psychosocial field, foremost social workers and psychologists. This paper
      deals with patients' motives for seeing a psychologist. METHODS: The case books
      for all patients who had met with the psychologist at a department of oncology in
      Sweden during a 10-year period were read through and categorised according to
      what the patients wanted to talk about. RESULTS: The most commonly found motives
      were in sliding order: coping with anxiety and worries caused by the disease;
      dealing with relational problems in life outside the disease; dealing with
      relational problems actualised by the disease; living with a malignant disease
      despair in a new life situation; and finally dealing with a particular problem.
      CONCLUSION: Patients seeing a psychologist in oncology do not just ask for help
      to come to terms with anxiety and worries. More than a third of the patients
      wanted to talk about distressing relationships, which were not connected to, or
      only remotely connected to the cancer disease. Patients have different needs and
      competence in different psychological treatment perspectives is therefore
      important. The found diversity of motives bears impact on the external validity
      of screening instruments for distress and randomised controlled intervention
      studies.

PMID- 19382117
TI  - Thoracoscopic cell sheet transplantation with a novel device.
AB  - Regenerative medicine with transplantable cell sheets fabricated on temperature
      responsive culture surfaces has been successfully achieved in clinical
      applications, including skin and cornea treatment. Previously, we reported that
      transplantation of fibroblast cell sheets to wounded lung had big advantages for
      sealing intraoperative air leaks compared with conventional materials. Here, we
      report a novel device for minimally invasive transplantation of cell sheets in
      endoscopic surgery, such as video-assisted thoracoscopic surgery (VATS). The
      novel device was designed with a computer-aided design (CAD) system, and the
      three-dimensional (3D) data were transferred to a 3D printer. With this rapid
      prototyping system, the cell sheet transplantation device was fabricated using a
      commercially available photopolymer approved for clinical use. Square cell sheets
      (24 x 24 mm) were successfully transplanted onto wound sites of porcine lung
      placed in a human body model, with the device inserted through a 12 mm port. Such
      a device would enable less invasive transplantation of cell sheets onto a wide
      variety of internal organs.

PMID- 19382114
TI  - Prenatal features of Costello syndrome: ultrasonographic findings and atrial
      tachycardia.
AB  - OBJECTIVE: Delineate prenatal features of Costello syndrome (caused by HRAS
      mutations), which consists of mental retardation, facial, cardiovascular, skin,
      and musculoskeletal anomalies, and tumor predisposition. METHODS: Literature and
      new cases classified as Group I (pre-HRAS), Group II (HRAS confirmed), and Group
      III (HRAS confirmed in natural history study, plus three contributed cases).
      RESULTS: Polyhydramnios occurred in most (mean 79%) pregnancies of cases in
      Groups I (98), II (107), and III (17); advanced paternal age and prematurity were
      noted in approximately half. Less frequent were nuchal thickening, ascites,
      shortened long bones, abnormal hand posture, ventriculomegaly, macrosomia, and
      macrocephaly. Fetal arrhythmia occurred in nine cases (six supraventricular or
      unspecified tachycardia, one unspecified arrhythmia, and two premature atrial
      contractions, PACs); excluding three new cases and two with PACs, the estimated
      prenatal frequency is 4/222 (2%). CONCLUSION: Costello syndrome can be suspected
      prenatally when polyhydramnios is accompanied by nuchal thickening, hydrops,
      shortened long bones, abnormal hand posture, ventriculomegaly, large size, and
      macrocephaly, and especially fetal atrial tachycardia. Consideration should be
      given for timely prenatal diagnostic studies for confirmative HRAS gene mutations
      and for maternal treatment of serious fetal arrhythmia.

PMID- 19382118
TI  - Smooth muscle tissue engineering for hybrid tubular organs: scanning electron
      microscopic investigations of cell interactions with collagen scaffolds.
AB  - Tissue engineering of transplantable tubular tissue necessitates a composite
      approach to assembling the individual components. In the engineering of tubular
      structures (gastrointestinal, urogenital and vascular tissues) there is a demand
      for smooth muscle tissue in addition to the primary organ-specific tissue. This
      study aims to investigate the interaction of smooth muscle cells on bovine
      collagen scaffolds cross-linked with glutaraldehyde under in vitro conditions,
      using scanning electron microscopy. The density of tissue generated over the 8
      week period was demonstrated in terms of: (a) scaffold coverage and attachment;
      (b) cell density; (c) cell viability deep inside the scaffolds; and (d) cell
      differentiation.

PMID- 19382120
TI  - Guidelines for the conduct of human embryonic stem cell research.
AB  - This appendix provides a summary of and links to the ISSCR Guidelines for the
      Conduct of Human Embryonic Stem Cell Research and supporting documents.

PMID- 19382119
TI  - Comparative chondrogenesis of human cell sources in 3D scaffolds.
AB  - Cartilage tissue can be engineered by starting from a diversity of cell sources,
      including stem-cell based and primary cell-based platforms. Selecting an
      appropriate cell source for the process of cartilage tissue engineering or repair
      is critical and challenging, due to the variety of cell options available. In
      this study, cellular responses of isolated human chondrocytes, human embryonic
      stem cells and mesenchymal stem cells (MSCs) derived from three sources, human
      embryonic stem cells, bone marrow and adipose tissue, were assessed for
      chondrogenic potential in 3D culture. All cell sources were characterized by FACS
      analysis to compare expression of some surface markers. The cells were
      differentiated in two different biomaterial matrices, silk and chitosan
      scaffolds, in the presence and absence of bone morphogenetic protein 6 (BMP6),
      along with the standard chondrogenic differentiating factors. Embryonic stem
      cells-derived MSCs showed unique characteristics, with preserved chondrogenic
      phenotype in both scaffolds with regard to chondrogenesis, as determined by real
      time RT-PCR, histological and microscopical analyses. After 4 weeks of
      cultivation, embryonic stem cells-derived MSCs were promising for chondrogenesis,
      particularly in the silk scaffolds with BMP6. The results suggest that cell
      source differences are important to consider with regard to chondrogenic
      outcomes, and among the variables addressed here the human embryonic stem cells
      derived MSCs were the preferred cell source.

PMID- 19382121
TI  - ISSCR Guidelines for the Clinical Translation of Stem Cells.
AB  - This appendix provides a summary of and links to the ISSCR Guidelines for the
      Clinical Translation of Stem Cells and supporting documents.

PMID- 19382122
TI  - Isolation and differentiation of Xenopus animal cap cells.
AB  - Xenopus is used as a model animal for investigating the inductive events and
      organogenesis that occur during early vertebrate development. Given that they are
      easy to obtain in high numbers and are relatively large in size, Xenopus embryos
      are excellent specimens for performing manipulations such as microinjection and
      microsurgery. The animal cap, which is the area around the animal pole of the
      blastula, is destined to form the ectoderm during normal development. However,
      these cells retain pluripotentiality and upon exposure to specific inducers, the
      animal cap can differentiate into neural, mesodermal, and endodermal tissues. In
      this sense, the cells of the animal cap are equivalent to mammalian embryonic
      stem cells. In this unit, the isolation and differentiation of animal cap cells,
      the so-called animal cap assay, is described. Useful methods for analyzing the
      mechanism of animal cap differentiation at the molecular level are also
      described.

PMID- 19382123
TI  - Heterokaryon-based reprogramming for pluripotency.
AB  - Embryonic stem (ES) cells have the ability to self-renew, execute multiple
      lineage paths, and dominantly reprogram differentiated cells upon cell fusion.
      Here, we describe an approach that reprograms human B lymphocytes toward
      pluripotency by generating inter-species heterokaryons with mouse ES cells. This
      induces a human ES-specific gene expression profile, in which the extent and the
      rapidity of conversion allows us to compare the capacity of different mouse ES
      cell lines to dominantly induce pluripotency. This approach, coupled with
      pharmacological inhibition, gene knock-out, or knock-down permits factors that
      are required to directly induce reprogramming to be defined individually, as well
      as in combination. Experimental heterokaryons provide a simple and tractable
      approach to address the mechanisms underlying direct reprogramming to
      pluripotency. The procedure requires 5 days to complete.

PMID- 19382124
TI  - Effects of orally administered lavender essential oil on responses to anxiety
      provoking film clips.
AB  - BACKGROUND: Lavender odour is commonly used to alleviate mild anxiety. Double
      blind studies are difficult to conduct with odours, and there are few reliable
      investigations of lavender's efficacy. METHOD: Orally administered lavender
      capsules (placebo, 100, 200 microl) were tested in a randomised between-subjects
      (n = 97) double-blind study. Film clips were used to elicit anxiety. Measures
      included anxiety, State Trait Anxiety Inventory (STAI), mood, positive and
      negative affect scale (PANAS), heart rate (HR), galvanic skin response (GSR), and
      heart rate variation (HRV). Following baseline measurements capsules were
      administered. Participants viewed a neutral film clip, then an anxiety-provoking
      and light-hearted recovery film clip. RESULTS: For the 200 microl lavender dose
      during the neutral film clip there was a trend towards reduced state anxiety, GSR
      and HR and increased HRV. In the anxiety-eliciting film, lavender was mildly
      beneficial in females but only on HRV measures. In males sympathetic arousal
      increased during the anxiety film (GSR). HRV significantly increased at 200
      microl during all three film clips in females, suggesting decreased anxiety.
      CONCLUSION: These findings suggest that lavender has anxiolytic effects in humans
      under conditions of low anxiety, but these effects may not extend to conditions
      of high anxiety.

PMID- 19382126
TI  - Talking over the fence.

PMID- 19382127
TI  - Anorexia nervosa--irony, misnomer and paradox.
AB  - Anorexia nervosa is a condition full of irony and paradox. Perhaps the most
      enigmatic of these is that professionals tend to hold the same morbid
      preoccupation with weight, BMI and targets as do our patients. In this article we
      outline why we believe that an over-emphasis on weight/BMI and targets is
      inappropriate, misleading and potentially harmful. Although this view is not
      always greeted with enormous enthusiasm by some, others are relieved that this
      particular 'holy cow' is at last being challenged. It is important that we should
      all have an open mind to the possibility that one of the main tenets of our
      practice may actually be unhelpful. Some ancient wisdom is drawn upon to support
      this view.

PMID- 19382128
TI  - International survey on willingness-to-pay (WTP) for one additional QALY gained:
      what is the threshold of cost effectiveness?
AB  - Although the threshold of cost effectiveness of medical interventions is thought
      to be 20 000- 30 000 UK pounds in the UK, and $50 000-$100 000 in the US, it is
      well known that these values are unjustified, due to lack of explicit scientific
      evidence. We measured willingness-to-pay (WTP) for one additional quality
      adjusted life-year gained to determine the threshold of the incremental cost
      effectiveness ratio. Our study used the Internet to compare WTP for the
      additional year of survival in a perfect status of health in Japan, the Republic
      of Korea (ROK), Taiwan, Australia, the UK, and the US. The research utilized a
      double-bound dichotomous choice, and analysis by the nonparametric Turnbull
      method. WTP values were JPY 5 million (Japan), KWN 68 million (ROK), NT$ 2.1
      million (Taiwan), 23 000 UK pounds (UK), AU$ 64 000 (Australia), and US$ 62 000
      (US). The discount rates of outcome were estimated at 6.8% (Japan), 3.7% (ROK),
      1.6% (Taiwan), 2.8% (UK), 1.9% (Australia), and 3.2% (US). Based on the current
      study, we suggest new classification of cost-effectiveness plane and methodology
      for decision making.

PMID- 19382129
TI  - Antioxidant effect of diphenyl diselenide on oxidative stress caused by acute
      physical exercise in skeletal muscle and lungs of mice.
AB  - This study was designed to examine if diphenyl diselenide (PhSe)(2), an
      organoselenium compound, attenuates oxidative stress caused by acute physical
      exercise in skeletal muscle and lungs of mice. Swiss mice were pre-treated with
      (PhSe)(2) (5 mg kg(-1) day(-1)) for 7 days. At the 7th day, the animals were
      submitted to acute physical exercise which consisted of continuous swimming for
      20 min. The animals were euthanized 1 and 24 h after the exercise test. The
      levels of thiobarbituric acid reactive species (TBARS), non-protein thiols (NPSH)
      and ascorbic acid and the activity of catalase (CAT) were measured in the lungs
      and skeletal muscle of mice. Glycogen content was determined in the skeletal
      muscle of mice. Parameters in plasma (urea and creatinine) were determined. The
      results demonstrated an increase in TBARS levels induced by acute physical
      exercise in the skeletal muscle and lungs of mice. Animals submitted to exercise
      showed an increase in non-enzymatic antioxidant defenses (NPSH and ascorbic acid)
      in the skeletal muscle. In lungs of mice, activity of CAT was increased.
      (PhSe)(2) protected against the increase in TBARS levels and ameliorated
      antioxidant defenses in the skeletal muscle and lungs of mice submitted to
      physical exercise. These results indicate that acute physical exercise caused a
      tissue-specific oxidative stress in the skeletal muscle and lungs of mice.
      (PhSe)(2) protected against oxidative damage induced by acute physical exercise
      in mice.

PMID- 19382130
TI  - The MMSE orientation for time domain is a strong predictor of subsequent
      cognitive decline in the elderly.
AB  - BACKGROUND: The mini-mental state exam (MMSE) has been used to address questions
      such as determination of appropriate cutoff scores for differentiation of
      individuals with intact cognitive function from patients with dementia and rate
      of cognitive decline. However, little is known about the relationship of
      performance in specific cognitive domains to subsequent overall decline.
      OBJECTIVE: To examine the specific and/or combined contribution of four MMSE
      domains (orientation for time, orientation for place, delayed recall, and
      attention) to prediction of overall cognitive decline on the MMSE. METHODS:
      Linear mixed models were applied to 505 elderly nursing home residents (mean age
      = 85, > 12 years education = 27%; 79% F, mean follow-up = 3.20 years) to examine
      the relationship between baseline scores of these domains and total MMSE scores
      over time. RESULTS: Orientation for time was the only domain significantly
      associated with MMSE decline over time. Combination of poor delayed recall with
      either attention or orientation for place was associated with significantly
      increased decline on the MMSE. CONCLUSIONS: The MMSE orientation for time
      predicts overall decline on MMSE scores over time. A good functioning domain
      added to good functioning delayed recall was associated with slower rate of
      decline.

PMID- 19382131
TI  - PCR-product microarray based on polyacrylic acid-modified surface for SNP
      genotyping.
AB  - PCR-product microarray has great efficiency in SNP genotyping, mutation screening
      and epigenetic analyzing from a large number of samples. The current PCR-product
      microarray technology is mostly based on the 3-D gel microarray technologies due
      to its high loading capacity for PCR products, while there is little progress for
      PCR-product microarray on planar glass, which gives low background and convenient
      fabrication. In this study, we improved the PCR-product microarray on planar
      glass by employing a polyacrylic acid-covered slide. The raw amino-modified PCR
      products were simply precipitated with ethanol and directly spotted for DNA
      immobilization. Three detection methods of hybridization, solid-single base
      extension and solid-multiple bases elongation were carried out for single
      nucleotide variation identification on the PCR-product microarray. The
      experimental results showed that the high immobilization yield for raw PCR
      product was achieved, and the high specificity and high ratio of S/N for
      genotyping on the microarray were obtained. SNP genotyping of cytochrome P450 2D6
      gene in 30 individuals was successfully demonstrated. This study has
      significantly increased the performances of PCR-product microarray, which could
      improve its applications in SNP genotyping and mutation screening in large number
      of individuals.

PMID- 19382132
TI  - Introducing a new parameter for quality control of proteome profiles:
      consideration of commonly expressed proteins.
AB  - Interpretation of proteome profiling experiments largely relies on comparative
      analyses. False-positive identifications may cause fatal misinterpretation of
      data. On the other hand, proteome analysis may also suffer from false negatives,
      when proteins that are actually present are not detected. This circumstance may
      be as fatal as false-positive identifications and was hardly considered until
      now. Appropriate positive controls would facilitate quality assessment of
      proteome profiling experiments. Based on cell biology knowledge, our aim was to
      generate a list of commonly expressed proteins, which may serve as positive
      control. Following a pragmatic experimental strategy, we compared the cytoplasmic
      fractions of four largely differing kinds of cells, which were human DCs,
      endothelial cells, fibroblasts and keratinocytes. Proteome profiling was
      performed by 2D-PAGE in addition to shotgun analysis. By shotgun analysis, 665
      proteins were identified, which occurred in each of the four cells types; 360
      proteins of those were also detectable in the corresponding 2-D gels. We consider
      these proteins as common proteins. All shotgun analysis data, including mass
      fragmentation spectra of the corresponding peptides, are accessible via the
      proteomics identification database (http://www.ebi.ac.uk/pride). As expected,
      most of the common proteins could be clearly assigned to at least one of the
      following functional categories: chaperones, cytoskeleton, energy metabolism,
      redox regulation, nucleic acid processing, protein turnover, membrane transport,
      protein synthesis and signaling. We suggest that the present data may prove
      helpful for data assessment, quality control and interpretation of a large
      variety of experiments based on proteome profiling.

PMID- 19382133
TI  - Development and characterization of polyspecific anti-mitochondrion antibodies
      for proteomics studies on in toto tissue homogenates.
AB  - We describe the characterization of polyclonal antibodies directed against the
      whole mitochondrial subproteome, as obtained by hyperimmunization of rabbits with
      an organelle fraction purified from human skeletal muscle and lysed by
      sonication. After 2-DE separations with either blue native electrophoresis or IPG
      as first dimension and blotting, the polyspecific antibodies detect 113 proteins
      in human muscle mitochondria, representative of all major biochemical pathways
      and oxidative phosphorylation (OXPHOS) complexes, and cross-react with 28
      proteins in rat heart mitochondria. Using as sample cryosections of human muscle
      biopsies lysed in urea/thiourea/CHAPS, the mitochondrial subproteome can be
      detected against the background of contractile proteins. When comparing with
      controls samples from mitochondrial encephalomyopathy with lactic acidosis and
      stroke-like episodes patients, immunoblotting shows in the latter a drastic
      reduction for the subunits of OXPHOS complex I as well as an increase of several
      enzymes, including ATP synthase. This finding is the first evidence at the
      proteomic level of massive up-regulation in a number of metabolic pathways by
      which the affected tissues try to compensate for the deficit in the OXPHOS
      machinery.

PMID- 19382134
TI  - Fabrication and fluorescence imaging of human low-density lipoprotein coatings
      for highly efficient capillary electrophoresis separation of basic proteins.
AB  - Here we present a unique fabrication of capillary coatings by using a native
      protein-phospholipid assembly, human low-density lipoprotein (LDL). By taking
      advantage of its constituents of apoproteins and phospholipids, two types of LDL
      coatings (non-covalent and covalent) were constructed. The non-covalent LDL
      coatings were prepared through physical adsorption of its phospholipids on fused
      silica, and the covalent coatings were prepared through covalent bonding of its
      apoproteins with the aminopropyl-modified silica. These coatings were subjected
      to CE separation of basic proteins (lysozyme, cytochrome c, ribonuclease A, and
      alpha-chymotrypsinogen A). Although both types of the coatings display efficient
      separation of the four proteins while effectively inhibiting the undesirable
      adsorption, the covalent LDL coatings provide higher separation efficiency (0.67
      2.01 x 10(5) theoretical plates/m) and longer coating-life. Results also reveal
      that the LDL coatings can hydrophobically interact with proteins and provide
      options for tuning the separation selectivity of proteins besides their inherent
      electrophoretic mobility. By using SYPRO Orange staining and fluorescence
      imaging, the coverage and homogeneity of the LDL coatings along the capillary
      were further visually characterized. It was found that the coverage of LDL
      particles in the covalent coatings was much higher than that in the non-covalent
      coatings. To the best of our knowledge, this is the first report describing the
      enhanced CE protein separation by lipoprotein coating. In virtue of the
      apoproteins-phospholipids structure, the LDL coatings are potentially useful in
      various LDL-related binding studies and complex bio-analysis.

PMID- 19382135
TI  - Direct on-line analysis of neutral analytes by dual sweeping via complexation and
      organic solvent field enhancement in nonionic MEKC.
AB  - Conventionally, neutral compounds cannot be separated by nonionic micelle
      capillary electrophoresis. In this report, the development of a novel on-line
      preconcentration technique combining dual sweeping based on complexation and
      organic solvent field enhancement is applied to the sensitive and selective
      analysis of three neutral glucosides: ginsenoside Rf, ginsenoside Rg1, and
      ginsenoside Re. Nonionic micelle detectability by CE is demonstrated through
      effective focusing of large sample volumes (up to 38% capillary length) using a
      dual sweeping mode. This results in a 50- to 130-fold improvement in the LODs
      relative to conventional injection method. Neutral compounds sweeping is examined
      in terms of analyte mobility dependence on borate complexation, solvent viscosity
      difference, and Brij-35 interaction. Enhanced focusing performance by this
      hyphenated method was demonstrated by a greater than fourfold reduction in
      glucoside bandwidth, as compared with common sweeping (devoid of organic solvent
      mediated sweeping method in the sample matrices). Moreover, separation
      efficiencies greater than a million theoretical plates can be achieved by
      sweeping large sample volumes into narrow zones. The designated method was also
      tested for its ability to determine the presence of glucosides in the crude
      extracts obtained from plant sample.

PMID- 19382137
TI  - Omic analyses unravels global molecular changes in the brain and liver of a rat
      model for chronic Sake (Japanese alcoholic beverage) intake.
AB  - The effects of chronic administration of Sake (Japanese alcoholic beverage,
      Nihonshu) on brain and liver of female F334 (Fisher) rats were surveyed via
      global omic analyses using DNA microarray, 2-DE, and proton nuclear magnetic
      resonance. Rats weaned at 4 wk of age were given free access to Sake (15%
      alcohol), instead of water. At 13 months of age, and 24 h after withdrawal of
      Sake supply, rats were sacrificed, and the whole brain and liver tissues
      dissected for analyses. In general, molecular changes in brain were found to be
      less than those in liver. Transcriptomics data revealed 36 and 9, and 80 and 62
      up- and down-regulated genes, in the brain and liver, respectively, with binding
      and catalytic activity gene categories the most prominently changed. Results
      suggested Sake-induced fragility of brain and liver toxicity/damage, though no
      significant abnormalities in growth were seen. At protein level, a striking
      decrease was found in the expression of NADH dehydrogenase (ubiquinone) Fe-S
      protein 1 in brain, suggesting attenuation of mitochondrial metabolism. In liver,
      results again suggested an attenuation of mitochondrial function and, in
      addition, glycoproteins with unknown function were induced at protein and gene
      levels, suggesting possible changes in glycoprotein binding in that organ.
      Metabolomic analysis of brain revealed significant increases in valine,
      arginine/ornithine, alanine, glutamine, and choline with decreases in isoleucine,
      N-acetyl aspartate, taurine, glutamate, and gamma aminobutyric acid. Our results
      provide a detailed inventory of molecular components of both brain and liver
      after Sake intake, and may help to better understand effects of chronic Sake
      drinking.

PMID- 19382138
TI  - Evidence for an association of the big five personality factors with recurrence
      of depressive symptoms in later life.
AB  - OBJECTIVES: Although it is well known that recurrence of late-life depression is
      very common, little is known about the characteristics of older people who are
      vulnerable for recurrence. In order to identify characteristics of those who are
      at risk, the present study aimed to investigate the strength of the associations
      of the big five personality factors with recurrence in later life. Secondly, we
      studied whether there are gender and age differences in the strength of these
      associations. METHODS: Using data from the longitudinal aging study Amsterdam
      (LASA) a subsample with clinically relevant depressive symptoms at one or more of
      the first three LASA-cycles, but who had recovered at the fourth cycle, was
      approached to participate in a fifth cycle to determine recurrence (n = 92).
      Respondents completed self-report questionnaires on personality (NEO-FFI) and
      depression (CES-D). By means of logistic regression analyses the associations
      between the Big Five and recurrence of depression at fifth cycle was
      investigated. RESULTS: 58 (63%) had a recurrence of depressive symptoms. A high
      level of neuroticism was significantly associated with recurrence. No gender
      differences or age-related differences in strength of the associations of
      personality with recurrence were found. CONCLUSION: In later life, neuroticism
      still is associated with the recurrence of depression. Efforts to prevent
      recurrence of late-life depression should focus on those with high levels of
      neuroticism and future research should aim at further unravelling the association
      between depression and personality in later life.

PMID- 19382140
TI  - Discrimination of extant Pan species and subspecies using the enamel-dentine
      junction morphology of lower molars.
AB  - Previous research has demonstrated that species and subspecies of extant
      chimpanzees and bonobos can be distinguished on the basis of the shape of their
      molar crowns. Thus, there is potential for fossil taxa, particularly fossil
      hominins, to be distinguished at similar taxonomic levels using molar crown
      morphology. Unfortunately, due to occlusal attrition, the original crown
      morphology is often absent in fossil teeth, and this has limited the amount of
      shape information used to discriminate hominin molars. The enamel-dentine
      junction (EDJ) of molar teeth preserves considerable shape information,
      particularly in regard to the original shape of the crown, and remains present
      through the early stages of attrition. In this study, we investigate whether the
      shape of the EDJ of lower first and second molars can distinguish species and
      subspecies of extant Pan. Micro-computed tomography was employed to non
      destructively image the EDJ, and geometric morphometric analytical methods were
      used to compare EDJ shape among samples of Pan paniscus (N = 17), Pan troglodytes
      troglodytes (N = 13), and Pan troglodytes verus (N = 18). Discriminant analysis
      indicates that EDJ morphology distinguishes among extant Pan species and
      subspecies with a high degree of reliability. The morphological differences in
      EDJ shape among the taxa are subtle and relate to the relative height and
      position of the dentine horns, the height of the dentine crown, and the shape of
      the crown base, but their existence supports the inclusion of EDJ shape
      (particularly those aspects of shape in the vertical dimension) in the systematic
      analysis of fossil hominin lower molars.

PMID- 19382143
TI  - Bacterial consortium proteomics under 4-chlorosalicylate carbon-limiting
      conditions.
AB  - In this study, the stable consortium composed by Pseudomonas reinekei strain MT1
      and Achromobacter xylosoxidans strain MT3 (cell numbers in proportion 9:1) was
      under investigation to reveal bacterial interactions that take place under severe
      nutrient-limiting conditions. The analysis of steady states in continuous
      cultures was carried out at the proteome, metabolic profile, and population
      dynamic levels. Carbon-limiting studies showed a higher metabolic versatility in
      the community through upregulation of parallel catabolic enzymes (salicylate 5
      hydroxylase and 17-fold on 2-keto-4-pentenoate hydratase) indicating a possible
      alternative carbon routing in the upper degradation pathway highlighting the
      effect of minor proportions of strain MT3 over the major consortia component
      strain MT1 with a significant change in the expression levels of the enzymes of
      the mainly induced biodegradation pathway such as salicylate 1-hydroxylase and
      catechol 1,2-dioxygenase together with important changes in the outer membrane
      composition of P. reinekei MT1 under different culture conditions. The study has
      demonstrated the importance of the outer membrane as a sensing/response
      protective barrier caused by interspecies interactions highlighting the role of
      the major outer membrane proteins OprF and porin D in P. reinekei sp. MT1 under
      the culture conditions tested.

PMID- 19382144
TI  - Growth factors and glucose homeostasis in diabetic rats: effects of exercise
      training.
AB  - To investigate the alterations of glucose homeostasis and variables of the
      insulin-like growth factor-1 (IGF-1) growth system in sedentary and trained
      diabetic (TD) rats, Wistar rats were divided into sedentary control (SC), trained
      control (TC), sedentary diabetic (SD), and TD groups. Diabetes was induced by
      Alloxan (35 mg kg(-1) b.w.). Training program consisted of swimming 5 days week(
      1), 1 h day(-1), during 8 weeks. Rats were sacrificed and blood was collected for
      determinations of serum glucose, insulin, growth hormone (GH), IGF-1, and IGF
      binding protein-3 (IGFBP-3). Muscle and liver were removed to evaluate glycogen
      content. Cerebellum was extracted to determinate IGF-1 content. Diabetes
      decreased serum GH, IGF-1, IGFBP-3, liver glycogen, and cerebellum IGF-1 peptide
      content in baseline condition. Physical training recovered liver glycogen and
      increased serum and cerebellum IGF-1 peptide in diabetic rats. Physical training
      induces important metabolic and hormonal alterations that are associated with an
      improvement in glucose homeostasis and serum and cerebellum IGF-1 concentrations.

PMID- 19382145
TI  - Arsenic speciation in cattail (Typha latifolia) using chromatography and mass
      spectrometry.
AB  - Typha latifolia, commonly known as cattail, is widely used as traditional food
      and medicinal ingredients by indigenous people. There have been concerns over the
      high levels of total arsenic in cattail plants, but the chemical species of
      arsenic in cattail have not been characterized. We describe here the
      determination of arsenic species in the various compartments of cattail. Average
      concentrations of total arsenic from 9 to 19 cattail plants were 1120 microg/kg
      (range 68-2600 microg/kg) in the fine (hairy) roots, 575 microg/kg (range 16
      1400) in the skin of tuber, 26 microg/kg (range 2-82) in the core of the tuber, 6
      microg/kg (range 5-12) in the stem, and 420 microg/kg (range 4-1970) in the whole
      tuber. Speciation analysis using strong anion exchange, ion pairing, and strong
      cation exchange chromatography separation with MS detection revealed the presence
      of inorganic arsenite, arsenate, dimethylarsinic acid, and monomethylarsonic
      acid. The two inorganic arsenic species accounted for >80% of the total arsenic.
      Further analyses of arsenic and iron concentrations showed a strong correlation
      between arsenic and iron in the fine roots and skin. These results suggest that
      arsenic and iron are colocalized (codeposited) in the skin of the cattail plants,
      consistent with the previous findings. The level of exposure to arsenic from the
      use of cattail as food and medicine can be substantially reduced by removing the
      skin of cattail.

PMID- 19382146
TI  - Impact of arsenic on nucleotide excision repair: XPC function, protein level, and
      gene expression.
AB  - The ubiquitous occurrence of the human carcinogen arsenic results in multiple
      exposure possibilities to humans. The human diet, especially drinking water, is
      the primary source of inorganic arsenic intake in the general population. The
      ingested arsenic is metabolized to methylated derivatives; some of these
      metabolites are today considered to be more toxic than the inorganic species.
      Various modes of action have been proposed to contribute to arsenic
      carcinogenicity; inhibition of nucleotide excision repair (NER), removing DNA
      helix distorting DNA adducts induced by environmental mutagens, is likely to be
      of primary importance. Here, we report that arsenite and its metabolite
      monomethylarsonous acid (MMA(III)) strongly decreased expression and protein
      level of Xeroderma pigmentosum complementation group C (XPC), which is believed
      to be the principle initiator of global genome NER. This led to diminished
      association of XPC to sites of local UVC damage, resulting in decreased
      recruitment of further NER proteins. Additionally Xeroderma pigmentosum
      complementation group E protein (XPE) expression was reduced, which encodes for
      another important NER protein and similarly to XPC is regulated by the activity
      of the transcription factor p53. In summary, our data demonstrate that in human
      skin fibroblasts arsenite and even more pronounced MMA(III) interact with XPC
      expression, resulting in decreased XPC protein level and diminished assembly of
      the NER machinery.

PMID- 19382147
TI  - Presence of arsenic in agricultural products from arsenic-endemic areas and
      strategies to reduce arsenic intake in rural villages.
AB  - About 100 million rural people in Asia are exposed to arsenic (As)-polluted
      drinking water and agricultural products. Total and inorganic arsenic (t-As and i
      As) intake mainly depend on the quality of drinking and cooking waters, and
      amounts of seafood and rice consumed. The main problems occur in countries with
      poor water quality where the population depends on rice for their diet, and their
      t-As and i-As intake is high as a result of growing and cooking rice in
      contaminated water. Workable solutions to remove As from water and breeding rice
      cultivars with low As accumulation are being sought. In the meantime, simple
      recommendations for processing and cooking foods will help to reduce As intake.
      For instance, cooking using high volumes of As-free water may be a cheap way of
      reducing As exposure in rural populations. It is necessary to consider the
      effects of cooking and processing on t-As and i-As to obtain a realistic view of
      the risks associated with intake of As in As-endemic areas.

PMID- 19382148
TI  - Status of groundwater arsenic contamination in the state of West Bengal, India: a
      20-year study report.
AB  - Since 1988 we have analyzed 140 150 water samples from tube wells in all 19
      districts of West Bengal for arsenic; 48.1% had arsenic above 10 microg/L (WHO
      guideline value), 23.8% above 50 microg/L (Indian Standard) and 3.3% above 300
      microg/L (concentration predicting overt arsenical skin lesions). Based on
      arsenic concentrations we have classified West Bengal into three zones: highly
      affected (9 districts mainly in eastern side of Bhagirathi River), mildly
      affected (5 districts in northern part) and unaffected (5 districts in western
      part). The estimated number of tube wells in 8 of the highly affected districts
      is 1.3 million, and estimated population drinking arsenic contaminated water
      above 10 and 50 microg/L were 9.5 and 4.2 million, respectively. In West Bengal
      alone, 26 million people are potentially at risk from drinking arsenic
      contaminated water (above 10 microg/L). Studying information for water from
      different depths from 107 253 tube wells, we noted that arsenic concentration
      decreased with increasing depth. Measured arsenic concentration in two tube wells
      in Kolkata for 325 and 51 days during 2002-2005, showed 15% oscillatory movement
      without any long-term trend. Regional variability is dependent on sub-surface
      geology. In the arsenic-affected flood plain of the river Ganga, the crisis is
      not having too little water to satisfy our needs, it is the crisis of managing
      the water.

PMID- 19382149
TI  - Exaggerated benefits of rosuvastatin compared with other statins.

PMID- 19382150
TI  - Clarification to the www.qtdrugs.org updated lists.

PMID- 19382151
TI  - Litter size and infant survivorship in wild groups of cotton-top tamarins
      (Saguinus oedipus) in Colombia.
AB  - Cotton-top tamains (Saguinus oedipus) are a critically endangered primate found
      only in Colombia. Efforts to conserve this species are centered on developing
      effective management plans that integrate biological information regarding
      population dynamics and factors that influence their survival. This study
      documented infants born to wild cotton-top tamarin females from 1994-2008 at two
      distinct field sites in northern Colombia. Our studies have shown that wild
      cotton-top tamarins typically give birth to one litter each year and infant
      survival to 6 months of age was greater in the wild than has been reported in
      captive colonies. However, similar to reports from captive colonies, litter size
      of wild cotton-top tamarins ranges from 1-3 infants, with twin litters most
      common. Here we report the first occurrence of triplet litters in nearly 20 years
      of observing wild cotton-top tamarin groups. Over the first 3 months of life,
      wild-born infants exhibited highest mortality during the first week of life,
      similar to reports from captive colonies. Infant survival in the wild also
      increases with successive litters as it does in captivity. However, inter-birth
      interval, group size, and the number of adult males in the group did not appear
      to influence infant survival in the wild. The value of such long-term data from
      field studies aids in the information that can be used to model future population
      trends and develop effective conservation plans for this critically endangered
      primate.

PMID- 19382152
TI  - Sexual size dimorphism in Asian colobines revisited.
AB  - Asian colobines exhibit a wide range of sexual dimorphism in body mass. Some
      species are monomorphic, whereas others are strongly dimorphic. Strong sexual
      dimorphism is generally viewed as the consequence of intense male contest
      competition over access to mates, but this idea appears not to explain variation
      in sexual dimorphism in Asian colobines. Our results show that modular colobines,
      i.e. species in which social units aggregate into higher-level bands or often
      associate, have significantly higher levels of sexual dimorphism in body mass
      than the nonmodular ones. This finding was corroborated by means of
      phylogenetically controlled methods and multiple regression analyses. The results
      suggest that living in a modular society intensifies the contest competition
      among males, which is further exacerbated by the continuous presence of all-male
      units.

PMID- 19382153
TI  - Primary peptide folding dynamics observed with ultrafast temperature jump.

PMID- 19382154
TI  - In situ discrimination between axially complexed and ligand-free co porphyrin on
      Au(111) with tip-enhanced Raman spectroscopy.
AB  - Simultaneous chemical and topographic information about cobalt tetraphenyl
      porphyrin (CoTPP) adlayers formed on a Au(111) single crystal is obtained with
      tip-enhanced Raman (TER) spectroscopy. We distinguish in situ between sample
      areas covered with an ordered adlayer of CoTPP and areas covered with a
      spontaneously formed disordered phase. The Raman vibrational fingerprints
      collected from the nanometer-sized near-field region just below a scanning
      tunnelling microscope (STM) tip are correlated with the adsorbate structures seen
      in the STM images. We assign the TER spectral features of the disordered phase to
      CoTPP complexes with CO and/or NO axial ligands, whereas the TER spectrum
      obtained from the ordered phase does not show any indication of additional axial
      complexation of CoTPP.

PMID- 19382155
TI  - Coronary heart disease of females: lessons learned from nonhuman primates.
AB  - The cynomolgus monkey model has contributed to significant advances regarding the
      understanding of coronary artery atherosclerosis of females. There are currently
      8 million women in the United States living with heart disease, necessitating
      further study and understanding of this leading cause of morbidity and mortality
      for postmenopausal women. Specifically, studies involving the monkey model have
      allowed greater understanding of the effect of the stage of reproductive life,
      time since menopause, and the extent of subclinical atherosclerosis as
      determinates of estrogen-mediated effects on arteries. Utilizing the
      commonalities among monkeys and human beings, these studies have shown that
      postmenopausal atherosclerosis is associated with the premenopausal reproductive
      timeframe. In addition, monkey studies have shown that estrogen deficiency during
      the premenopausal stage is extremely relevant regarding the progression of
      atherosclerosis. After several postmenopausal years, however, studies have shown
      that estrogen has no beneficial effects on atherosclerosis progression and may,
      in fact, be deleterious. Studies using the monkey model are currently underway to
      investigate further uses and possibilities of postmenopausal hormone therapy for
      treating menopausal symptoms while protecting the breast and uterus and
      inhibiting the progression of coronary artery atherosclerosis. These studies will
      hopefully clarify the role of estrogen and eliminate the need for the possibly
      harmful progestin effects through the use of a highly selective estrogen receptor
      modulator.

PMID- 19382156
TI  - Repeatability of a dual gradient-recalled echo MRI method for monitoring post
      isometric contraction blood volume and oxygenation changes.
AB  - The purpose of this study was to assess the repeatability of a dual gradient
      recalled echo (GRE) muscle functional MRI technique. On 2 days, subjects (n = 8)
      performed 10 s isometric dorsiflexion contractions under conditions of: (1)
      maximal voluntary contraction (MVC), (2) 50% MVC (50% MVC), or (3) 50% MVC with
      concurrent proximal arterial cuff occlusion (50% MVC(cuff)). Functional MRI data
      were acquired using single-slice dual GRE (TR/TE = 1000/6, 46 ms)-echo planar
      imaging for 20 s before, during, and for 180 s after each contraction. The mean
      signal intensity (SI) time courses at each TE (SI(6) and SI(46), reflecting
      variations in blood volume and %HbO(2), respectively) from the tibialis anterior
      (TA) and extensor digitorum longus (EDL) muscles were characterized with the post
      contraction change in SI and the time-to-peak SI (DeltaSI and TTP, respectively).
      DeltaSI(6) following an MVC was 36% higher than that obtained after a 50% MVC (p
      = 0.048). For DeltaSI(6), the highest intraclass correlation coefficients (ICCs)
      were observed for the TA muscle in the 50% MVC and MVC conditions, with values of
      0.83 (p = 0.01) and 0.88 (p = 0.005), respectively. Bland-Altman plots revealed
      repeatability coefficients (RCs) for the 50% MVC and MVC conditions in the TA
      muscle of 1.9 and 1.4, respectively. The most repeatable measures for DeltaSI(46)
      were obtained for the 50% MVC and MVC conditions in the EDL muscle (p = 0.01 and
      p = 0.04, respectively). Bland-Altman plots revealed RC's for 50% MVC and MVC
      conditions in the EDL muscle of 3.9 and 5.7, respectively. DeltaSI(6) and
      DeltaSI(46) increased as a function of the contraction intensity. The
      repeatability of the method depends on the muscle and contraction condition being
      evaluated, and in general, is higher following an MVC.

PMID- 19382157
TI  - Free Vascularized Fibular Grafting for treatment of osteonecrosis of the femoral
      head secondary to hip dislocation.
AB  - Traumatic dislocation of the hip results in osteonecrosis of the femoral head
      (ONFH) or avascular necrosis (AVN) in approximately 40% of patients. This high
      energy event causes an ischemic insult to the femoral head that may lead to ONFH.
      Here, we investigate use of Free-Vascularized Fibular Grafting (FVFG) in patients
      with ONFH after traumatic hip dislocation. Thirty-five patients with FVFG for
      this indication were reviewed (average follow-up 3.3 years, range 1-21). We
      reviewed patient injury statistics, demographics, preoperative radiographs, pre-
      and postoperative Harris Hip scores, complications, and rate of conversion to
      total hip arthroplasty (THA). The majority (81%) of our patients were young males
      (22 years) with ONFH diagnosed an average of 2 years after injury. The average
      preoperative Harris Hip score was 64.9 which improved by over 10 points to 76.1
      at 1-year follow-up. Seven of 35 patients required conversion to THA at an
      average of 45 (13-86) months postoperation. After a maximum follow up of 21
      years, the remainder of the patients retained their native hips and Harris Hip
      scores tended to show improved hip function.

PMID- 19382158
TI  - Three-dimensional multislice spiral computed tomographic angiography: a
      potentially useful tool for safer free tissue transfer to complicated regions.
AB  - Three-dimensional multislice spiral computed tomographic angiography (3D-MSCTA)
      is a minimally invasive method of vascular mapping. The aim of this study was to
      evaluate the clinical usefulness of this imaging technique in delineating the
      recipient vessels for safer free tissue transfer to complicated regions. 3D-MSCTA
      was performed preoperatively in 26 patients scheduled for free tissue transfer,
      in whom the availability of the recipient vessels were considered to be
      uncertain, and 23 of these were operated on. Radiographic and operative findings
      regarding the availability of the recipient vessels for anastomosis were
      correlated in 21 of these 23 patients. 3D-MSCTA yielded two false-positive
      results; anastomosis was not possible because of widespread atherosclerotic
      plaques and poor flow observed in the recipient arteries despite the good caliber
      observed in 3D-MSCTA images. 3D-MSCTA provides a noninvasive means of
      preoperatively assessing recipient site vessels for anatomic variations and
      suitability before free tissue transfer and enables the surgeon to establish an
      appropriate treatment plan. But it is not 100% reliable yet and the possibility
      of false-positive results should be kept in mind, especially inthe patients with
      peripheral vascular disease. 3D-MSCTA has the potential to replace digital
      subtraction angiography for planning of microvascular reconstructions and newer
      devices with higher resolutions will probably increase the reliability of this
      technique. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009.

PMID- 19382159
TI  - SOX9 is not required for the cellular events of testicular organogenesis in XX
      mole ovotestes.
AB  - Mammalian sex determination is the genetic process that commits the
      undifferentiated bipotential gonads to develop as either testes or ovaries. The
      differentiation of SOX9-expressing Sertoli cells is assumed to be necessary to
      initiate testis development. Insectivorous moles of the genus Talpa represent a
      unique case of generalized true hermaphroditism, as XX female moles
      constitutively develop two ovotestes instead of normal ovaries. In this work, we
      have investigated the expression patterns of a number of genes known to play key
      roles in gonad organogenesis, throughout the entire process of ovotestis
      development in female moles. Molecular and morphological evidence are provided
      that these ovotestes contain primary medullary testis-like cords, Leydig cells,
      peritubular myoid cells, and a testis-specific vasculature, but no Sertoli cells.
      Our results show for the first time that SOX9 is not required for the formation
      of the primary testis cords, but it is necessary for the maintenance and
      subsequent development of these cords. In addition, the expression pattern of
      WNT4 in male and female moles indicates that this gene inhibits Leydig cell
      differentiation and, contrary to the proposed scenario in the mouse, it is not
      required for the colonization and survival of primordial germ cells. According to
      our data, mole ovotestes result from a process of PDGFRalpha-mediated mesonephric
      cell migration, which occurs simultaneously in both sexes. The fact that FST
      remains inactive during the critical stages of female gonad development, explains
      the lack of migration inhibition, and may be a consequence of improper WNT4
      signalling in the mole.

PMID- 19382160
TI  - Development of a field-friendly technique for fecal steroid extraction and
      storage using the African wild dog (Lycaon pictus).
AB  - Hormonal analysis provides information about wildlife populations, but is
      difficult to conduct in the field. Our goal was to develop a rapid and effective
      field method for fecal steroid analysis by comparing: (1) three extraction
      methods (laboratory (LAB), homogenize (HO) and handshake (HS)) and (2) two
      storage methods (solid-phase extraction (SPE) tubes vs. plastic tubes (PT)).
      Samples (n=23) from captive African wild dogs (Lycaon pictus) were thoroughly
      mixed, three aliquots of each were weighed ( approximately 0.5 g) and 5 ml of 90%
      ethanol was added. For LAB, samples were agitated (mixer setting 60; 30 min),
      centrifuged (1,500 rpm; 20 min) and poured into glass tubes. Or aliquots were HO
      (1 min) or HS (1 min) and poured through filter paper into glass tubes. Samples
      were split, analyzed for corticosterone (C) and testosterone (T) metabolites
      using enzyme immunoassays or stored in SPE or PT. Samples were stored (room
      temperature) for 30, 60 or 180 days, reconstituted in buffer and analyzed. Mean C
      and T recoveries of HO were greater (P=0.03) than HS compared with LAB, which was
      similar to HO (P>0.05). After 30 days <21% of C and T was recovered from SPE, but
      approximately 100% of each was recovered from HO-PT and HS-PT. Similarly, after
      60 and 180 days, approximately 100% of C and T was recovered from HO-PT and HS
      PT. Results demonstrated that, for C and T, HO was more comparable (P<0.001) to
      LAB than HS and PT storage was more efficient than SPE (P<0.001).

PMID- 19382161
TI  - Treatment of avulsion injury of three fingers with a compound thoracodorsal
      artery perforator flap including serratus anterior fascia.
AB  - Complete degloving injury of three digits not amenable to revascularization may
      leave poor cosmetic and functional results. We used a compound thoracodorsal
      artery perforator (TDAP) flap in a 34-year-old, right-handed, male worker with
      traumatic degloving injury. The flap consisted of a thin nonbulky skin component
      isolated on two perforators in combination with serratus fascia, both pedicled on
      the thoracodorsal vessels. The mobility of the two flap components allowed the
      palmar and dorsal part of the fingers to be reconstructed without relying on
      multiple flaps or anastomoses. The skin component of the TDAP flap was
      transferred to the palmar defect, the serratus fascia flap to the dorsal part of
      the fingers and sutured loosely. Coverage of the serratus anterior fascia was
      done with split-thickness skin graft. Both components of the flap survived
      completely. One month after the first operation, the surgical syndactyly between
      middle and ring finger was separated, one month later the syndactyly between the
      ring and little finger. Good coverage of the soft tissue defects with good
      function could be achieved. There were no donor-site problems. Therefore, we
      consider the compound TDAP flap as a useful method that provides functional and
      cosmeticcoverage of severe avulsion injury of multiple digits. (c) 2009 Wiley
      Liss, Inc. Microsurgery, 2009.

PMID- 19382162
TI  - Lip replantation and delayed inset after a dog bite: a case report and literature
      review.
AB  - Dog bites to the face are common in children and often involve amputation of the
      lip or cheek resulting in a devastating facial injury. When feasible,
      replantation of the amputated lip segment provides the optimal cosmetic outcome.
      Here, we present the case of a partial upper lip replantation with delayed inset
      as a new treatment option. Revascularization of the central upper lip segment was
      enabled by anastomosis to a single labial artery. Inset compression at the time
      of initial closure caused arterial insufficiency. Therefore, a delayed,
      sequential inset was performed over the following 2 weeks resulting in an
      esthetically and functionally successful replantation. A comprehensive review of
      the literature on published lip replantation techniques is also provided and
      discussed. We add delayed inset to the armamentarium of the microsurgeon when
      faced with these difficult injuries.

PMID- 19382163
TI  - A new, custom-made device for flap protection in experimental rats.

PMID- 19382164
TI  - Use of the arcade vessels after disruption of the vascular pedicle of pedicled
      jejunum transfer for a recurrent esophageal cancer patient.

PMID- 19382165
TI  - A system for monitoring and improving animal visibility and its implications for
      zoological parks.
AB  - With the growing trend in zoos to build complex, naturalistic exhibits comes the
      potential for exhibits to be so densely vegetated or complex that animals are not
      easily seen by zoo visitors. This can negatively impact the visitor's visiting
      experience and the zoo's ability to communicate conservation and education
      messages. Over the past 9 years, Disney's Animal Kingdom has developed a process
      for monitoring and improving the visibility of animals on display to the public.
      This animal visibility process utilizes a data collection system whereby
      systematic observations are collected each week. The percentage of observations
      where at least one animal was visible is recorded for each species and compared
      to an 80% visibility criterion. Species that do not reach this criterion for 4
      consecutive weeks are discussed at animal management meetings. If the problems
      associated with animal visibility cannot be easily solved, the animal-care teams
      partner with the research team to conduct a second process, called the Visibility
      Issues Process. This process provides additional information for the animal-care
      team to utilize in developing a plan to improve visibility. Although the
      processes described here are specific to the infrastructure at Disney's Animal
      Kingdom, the basic concepts of (1) a formalized visibility data collection
      process, (2) a visibility criterion to which managers of species are held
      accountable, and (3) a process for planning to improve animal visibility without
      negatively impacting animal welfare are fundamental concepts that can be
      developed at individual institutions and incorporated into that zoo's existing
      infrastructure.

PMID- 19382167
TI  - Conformational analysis of a peptide approximating the HCCH motif in HIV-1 Vif.
AB  - Virion infectivity factor (Vif) is an accessory protein encoded by HIV-1. Vif
      recruits a Cul5-based ubiquitin ligase that targets APOBEC3G, a host-encoded
      antiviral enzyme, for proteasomal degradation. The C-terminus of Vif contains a
      conserved His-X(5)-Cys-X(17-18)-Cys-X(3-5)-His (HCCH) motif that binds zinc and
      interacts with Cul5. In this study, CD spectroscopy, fluorescence spectroscopy,
      light scattering, and zinc binding assays were used to examine the conformational
      properties of HCCHp, a 42-amino acid peptide encompassing the HCCH motif. A
      single tryptophan residue was engineered into HCCHp to probe local structural
      changes induced by zinc binding. Zinc binding increased burial of the Trp residue
      from solvent and increased tertiary packing. The solvent 2,2,2-trifluoroethanol
      (TFE) induced the formation of an alpha-helical conformation of HCCHp with a
      midpoint of 20% (vol/vol) and inhibited zinc-induced aggregation of HCCHp. TFE
      titration data were sigmoidal, consistent with the cooperative nature of helix
      formation. Zinc binding to HCCHp in 30% TFE solutions was cooperative and
      weakened the TFE-induced structure. In 80% TFE solutions this cooperativity was
      lost, suggesting a mechanism in which monomeric and oligomeric peptide forms
      display different affinities for zinc. TFE weakened zinc binding to HCCHp by two
      orders of magnitude relative to the zinc binding affinity measured in aqueous
      solvent. The data suggest that HCCHp conformation and zinc binding affinity are
      tightly coupled. We propose that the lack of intrinsic structure in the HCCH
      motif may be important for Vif's function as an E3 ubiquitin ligase adaptor
      protein.

PMID- 19382168
TI  - Cytologic, flow cytometry, and molecular assessment of lymphoid infiltrate in
      fine-needle cytology samples of Hashimoto thyroiditis.
AB  - BACKGROUND: The thyroidal lymphoid infiltrate (TLI) in Hashimoto thyroiditis (HT)
      represents the substrate from which thyroid lymphoma may arise. The objective of
      the current study was to classify the TLI in HT by comparing the cytologic
      features with flow cytometry (FC) data and evaluating the kappa/lambda light
      chain ratio and its molecular assessment. METHODS: Fine-needle aspiration
      cytology (FNAC) was performed in 34 patients with HT with nodular or diffuse
      palpable enlargement of the gland. Two or 3 passes were performed to prepare
      traditional smears, FC, and immunophenotyping, and RNAlater suspensions for
      molecular assessment. FC was performed using the following antibodies: CD3, CD5,
      CD4, CD8, CD10, CD19, and kappa and lambda light chains. In 4 cases, high
      molecular weight DNA was extracted and used for polymerase chain reaction (PCR)
      to amplify the variable diversity joining region of the heavy chain
      immunoglobulin (Ig) genes (IgH). Statistical analysis was performed to evaluate
      possible associations between clinical ultrasound presentation, cytologic
      pattern, and TLI phenotype. Light chain expression was evaluated as the
      percentage of the expressing cells (</=20% and >20%) and as the kappa/lambda
      ratio. RESULTS: Smears were classified as "lymphocytic," "lymph node-like," or
      "mixed." FC demonstrated T cells (CD3 positive [+], CD5+) in all cases, and T
      cells and B cell (CD19+, CD10+/-) lymphocytes in 22 cases. Light chains were
      expressed in 30 cases (in <20% of the gated cells in 13 cases and in >20% of the
      gated cells in 17 cases). Five cases demonstrated small kappa/lambda ratio
      imbalances and PCR analysis demonstrated diffuse bands in the gel and Gaussian
      curves at the heteroduplex. Statistical analysis indicated significant
      associations between the "lymphocytic" pattern and T-cell phenotype and between
      the "lymph node-like" pattern and B-cell phenotype. A significant association
      also was observed between light chain restriction and low light chain expression
      (P < .005). CONCLUSIONS: The cytologic pattern of TLI in HT is quite
      representative of the clinical presentation and phenotypic cell type. Small light
      chain imbalances are not sustained by heavy chain Ig gene (IgH) rearrangements.
      FNA coupled with FC may contribute to making the distinction between florid TLI
      and non-Hodgkin lymphoma.

PMID- 19382169
TI  - A placebo arm is not always necessary in clinical trials of amyotrophic lateral
      sclerosis.
AB  - Riluzole is currently the only approved medication for amyotrophic lateral
      sclerosis (ALS). While other potential neuroprotective agents have been tested in
      clinical trials, none has been effective, and few symptomatic treatments have
      been studied. Randomized placebo-controlled trials are necessary to establish the
      effectiveness of a drug, but an increasing number of potential therapies combined
      with limited resources means that only a few drugs at a time can be tested for
      efficacy in ALS. Therefore, priority must be given to agents that show an
      advantage in early phase trials before proceeding to Phase III efficacy trials.
      New strategies are being used to screen different agents, along with their
      correct dose, in a variety of neurological illnesses, including ALS. Early phase
      trial designs conducted without a placebo arm improve efficiency, reduce cost,
      and appeal to patients. Dose-ranging, futility, and selection trials are examples
      of Phase I and II trial designs that can be conducted without placebo groups.

PMID- 19382170
TI  - Can we eliminate placebo in ALS clinical Trials?
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal disease with limited treatment
      options. Controlled studies are a necessary part of Phase II and Phase III
      assessments of proposed therapies. Due to the relatively small number of patients
      with ALS, several study designs have been proposed to improve the efficiency of
      Phase II studies. Some of these advocate the use of historical controls in place
      of placebo controls. However, the characteristics of historical controls may not
      mirror those of patients in the treatment group. Novel study designs can be used
      to decrease the number of patients required for Phase II studies. The use of
      placebo controls rather than historical controls in these novel study designs
      likely leads to better predictions of treatments that will be successful in Phase
      III studies. There is general agreement on the necessity of placebo controls in
      Phase III studies.

PMID- 19382172
TI  - Fixing the game: are between-silo differences in funding arrangements
      handicapping some interventions and giving others a head-start?
AB  - Given resource scarcity, not all potentially beneficial health services can be
      funded. Choices are made, if not explicitly, implicitly as some health services
      are funded and others are not. But what are the primary influences on those
      choices? We sought to test whether funding decisions are linked to cost
      effectiveness and to quantify the influence of funding arrangements and community
      values arguments. We tested this via empirical analysis of 245 Australian health
      care interventions for which cost-effectiveness estimates had been published. The
      likelihood of government funding was modelled as a function of cost
      effectiveness, patient/target group characteristics, intervention characteristics
      and publication characteristics, using multiple regression analysis. We found
      that higher cost effectiveness ratios were a significant predictor of funding
      rejection, but that cost effectiveness was not related to the level of funding.
      Intervention characteristics linked to funding and delivery arrangements and
      community values arguments were significant predictors of funding outcomes. Our
      analysis supports the hypothesis that funding and delivery arrangements influence
      both whether an intervention is funded and funding level; even after controlling
      for community values and cost effectiveness. It suggests that adopting partial
      priority setting processes without regard to opportunity cost can have the
      perverse effect of compounding allocative inefficiencies.

PMID- 19382171
TI  - Josephin domain of ataxin-3 contains two distinct ubiquitin-binding sites.
AB  - Joseph-Machado is an incurable neurodegenerative disease caused by toxic
      aggregation of ataxin-3, a ubiquitin-specific cysteine protease, involved in the
      ubiquitin-proteasome pathway and known to bind poly-ubiquitin chains of four or
      more subunits. The enzymatic site resides in the N-terminal josephin domain of
      ataxin-3. We have characterized the ubiquitin-binding properties of josephin and
      showed that, unexpectedly, josephin contains two contiguous but distinct
      ubiquitin-binding sites. One is close to the enzymatic cleft and exploits an
      induced fit mechanism, which involves a flexible helical hairpin; the other
      overlaps with the site involved in recognition of HHR23B, a protein involved in
      delivering proteolytic substrates to the proteasome. To gain a structural
      description of the system, we had to overcome the nontrivial problem of dealing
      with a weak ternary complex. This was done by designing josephin mutants, which
      retain only one binding site and by characterizing the complexes with
      complementary computational and experimental techniques. The presence of two
      ubiquitin-binding sites explains how ataxin-3 binds poly-ubiquitin chains and
      provides new insights into the molecular mechanism of ubiquitin recognition.

PMID- 19382173
TI  - Study on the inhibitory mechanism and binding mode of the hydroxycoumarin
      compound NSC158393 to HIV-1 integrase by molecular modeling.
AB  - Human immunodeficiency virus type 1 integrase (IN) is an essential enzyme in the
      life cycle of this virus and also an important target for the study of anti-HIV
      drugs. In this work, the binding modes of the wild type IN core domain and the
      two mutants, that is, W132G and C130S, with the 4-hydroxycoumarin compound
      NSC158393 were evaluated by using the "relaxed complex" molecular docking
      approach combined with molecular dynamics (MD) simulations. Based on the monomer
      MD simulations, both of the two substitutions affect not only the stability of
      the 128-136 peptides, but also the flexibility of the functional 140s loop. In
      principle, NSC158393 binds the 128-136 peptides of IN; however, the specific
      binding modes for the three systems are various. According to the binding mode of
      NSC158393 with WT, NSC158393 can effectively interfere with the stability of the
      IN dimer by causing a steric hindrance around the monomer interface.
      Additionally, through the comparative analysis of the MD trajectories of the wild
      type IN and the IN-NSC158393 complex, we found that NSC15893 may also exert its
      inhibitory function by diminishing the mobility of the function loop of IN. Three
      key binding residues, that is, W131, K136, and G134, were discovered by energy
      decomposition calculated with the Molecular Mechanics Generalized Born Surface
      Area method. Characterized by the largest binding affinity, W131 is likely to be
      indispensable for the ligand binding. All the above results are consistent with
      experiment data, providing us some helpful information for understanding the
      mechanism of the coumarin-based inhibitors.

PMID- 19382174
TI  - The indeterminate thyroid fine-needle aspiration: experience from an academic
      center using terminology similar to that proposed in the 2007 National Cancer
      Institute Thyroid Fine Needle Aspiration State of the Science Conference.
AB  - BACKGROUND: To date, thyroid fine-needle aspiration (FNA) has been used by
      clinicians as the screening test of choice to determine whether surgery is
      required and this is what the pathology report should communicate. Standard
      terminology for reporting thyroid FNA has not been implemented yet, and
      pathologists have used various reporting systems to communicate results. A
      significant source of confusion among both pathologists and clinicians has been
      the use of the indeterminate category. On the basis of an analysis of 1150
      thyroid FNAs in 2000, this institution modified the reporting of thyroid biopsy
      results into 6 categories, including unsatisfactory. The indeterminate category
      was separated into 3 subroups: 1) indeterminate for neoplasia (IND), 2)
      follicular neoplasm (FN), and 3) suspicious for malignancy (SUSP). Repeat FNA in
      6 months to 12 months was recommended for IND and surgery for FN and SUSP
      categories. METHODS: To determine the validity of this approach, the outcomes of
      this reporting system from July of 2000 to December of 2006 were analyzed. The
      IND category was used for 2 subsets of cases: (a) those that morphologically fall
      into the gray zone between adenomatoid nodule (AN) and FN, for Hurthle cell
      nodule (hyperplasia vs neoplasm), and chronic lymphocytic thyroiditis with
      concern for neoplasia; and (b) for suboptimal specimens due to low epithelial
      cellularity or collection artifacts. RESULTS: Among 5194 thyroid nodules, the IND
      category comprised 18%. FNA follow-up was done in 21% of IND cases: 58% were
      benign/negative and did not require surgery based on cytology alone. Surgical
      follow-up in 46% of IND showed 52% were benign/negative, and 42% were
      follicular/Hurthle cell adenomas. The surgical yield of malignancy in IND was low
      (6%) when compared with the FN category, which was 14% (more than 2x that of the
      IND category), and the SUSP category, which was 53% (almost 9x that of the IND
      category). CONCLUSIONS: A 6-tier reporting system for thyroid FNA was effective
      for determining which patients needed surgery versus follow-up FNA and also
      guided the clinician on the extent of surgery.

PMID- 19382175
TI  - Refinement of the primary hydration shell model for molecular dynamics
      simulations of large proteins.
AB  - A realistic representation of water molecules is important in molecular dynamics
      simulation of proteins. However, the standard method of solvating biomolecules,
      that is, immersing them in a box of water with periodic boundary conditions, is
      computationally expensive. The primary hydration shell (PHS) method, developed
      more than a decade ago and implemented in CHARMM, uses only a thin shell of water
      around the system of interest, and so greatly reduces the computational cost of
      simulations. Applying the PHS method, especially to larger proteins, revealed
      that further optimization and a partial reworking was required and here we
      present several improvements to its performance. The model is applied to systems
      with different sizes, and both water and protein behaviors are compared with
      those observed in standard simulations with periodic boundary conditions and, in
      some cases, with experimental data. The advantages of the modified PHS method
      over its original implementation are clearly apparent when it is applied to
      simulating the 82 kDa protein Malate Synthase G.

PMID- 19382176
TI  - All-electron LCAO calculations of the LiF crystal phonon spectrum: Influence of
      the basis set, the exchange-correlation functional, and the supercell size.
AB  - For the first time the convergence of the phonon frequencies and dispersion
      curves in terms of the supercell size is studied in ab initio frozen phonon
      calculations on LiF crystal. Helmann-Feynman forces over atomic displacements are
      found in all-electron calculations with the localized atomic functions (LCAO)
      basis using CRYSTAL06 program. The Parlinski-Li-Kawazoe method and FROPHO program
      are used to calculate the dynamical matrix and phonon frequencies of the
      supercells. For fcc lattice, it is demonstrated that use of the full supercell
      space group (including the supercell inner translations) enables to reduce
      essentially the number of the displacements under consideration. For Hartree-Fock
      (HF), PBE and hybrid PBE0, B3LYP, and B3PW exchange-correlation functionals the
      atomic basis set optimization is performed. The supercells up to 216 atoms (3 x 3
      x 3 conventional unit cells) are considered. The phonon frequencies using the
      supercells of different size and shape are compared. For the commensurate with
      supercell k-points the best agreement of the theoretical results with the
      experimental data is found for B3PW exchange-correlation functional calculations
      with the optimized basis set. The phonon frequencies at the most non-commensurate
      k-points converged for the supercell consisting of 4 x 4 x 4 primitive cells and
      ensures the accuracy 1-2% in the thermodynamic properties calculated (the
      Helmholtz free energy, entropy, and heat capacity at the room temperature).

PMID- 19382177
TI  - Size variation in early human mandibles and molars from Klasies River, South
      Africa: comparison with other middle and late Pleistocene assemblages and with
      modern humans.
AB  - Previous studies of the Middle Stone Age human remains from Klasies River have
      concluded that they exhibited more sexual dimorphism than extant populations, but
      these claims have not been assessed statistically. We evaluate these claims by
      comparing size variation in the best-represented elements at the site, namely the
      mandibular corpora and M(2)s, to that in samples from three recent human
      populations using resampling methods. We also examine size variation in these
      same elements from seven additional middle and late Pleistocene sites: Skhul,
      Dolni Vestonice, Sima de los Huesos, Arago, Krapina, Shanidar, and Vindija. Our
      results demonstrate that size variation in the Klasies assemblage was greater
      than in recent humans, consistent with arguments that the Klasies people were
      more dimorphic than living humans. Variation in the Skhul, Dolni Vestonice, and
      Sima de los Huesos mandibular samples is also higher than in the recent human
      samples, indicating that the Klasies sample was not unusual among middle and late
      Pleistocene hominins. In contrast, the Neandertal samples (Krapina, Shanidar, and
      Vindija) do not evince relatively high mandibular and molar variation, which may
      indicate that the level of dimorphism in Neandertals was similar to that observed
      in extant humans. These results suggest that the reduced levels of dimorphism in
      Neandertals and living humans may have developed independently, though larger
      fossil samples are needed to test this hypothesis.

PMID- 19382178
TI  - The history and composition of the Raymond A. Dart Collection of Human Skeletons
      at the University of the Witwatersrand, Johannesburg, South Africa.
AB  - The Raymond A. Dart Collection of Human Skeletons (Dart Collection) is housed in
      the School of Anatomical Sciences at the University of the Witwatersrand,
      Johannesburg, South Africa, and comprises one of the largest documented cadaver
      derived human skeletal assemblages in the world. This collection originated in
      the early 1920s as a result of the efforts of Raymond Dart and continues to grow.
      The skeletons included represent varied indigenous and immigrant populations from
      southern Africa, Europe and Asia. This contribution documents the history of the
      collection and provides an updated inventory and demographic assessment of this
      valuable research collection. According to a recent inventory the Dart Collection
      currently comprises 2,605 skeletons representing individuals from regional SA
      African (76%), White (15%), Coloured (4%) and Indian (0.3%) populations. A large
      proportion of the skeletons (71%) represent males. The recorded ages at death
      range from the first year to over 100 years of age, but the majority of
      individuals died between the ages of 20 and 70. The Dart Collection has been
      affected by collection procedures based on availability. All of the cadavers
      collected before 1958, and large proportions subsequently, were derived from
      unclaimed bodies in regional South African hospitals. Some details of
      documentation (age at death, population group) are estimates and some aspects of
      the collection demographics (sex ratios) do not closely reflect any living South
      African population. Our inventory and analysis of the Dart Collection is aimed to
      assist researchers planning research on the materials from this collection.

PMID- 19382179
TI  - Recent patterns in gastric cancer: a global overview.
AB  - Until the mid-1990s, gastric cancer has been the first cause of cancer death
      worldwide, although rates had been declining for several decades and gastric
      cancer has become a relatively rare cancer in North America and in most Northern
      and Western Europe, but not in Eastern Europe, Russia and selected areas of
      Central and South America or East Asia. We analyzed gastric cancer mortality in
      Europe and other areas of the world from 1980 to 2005 using joinpoint regression
      analysis, and provided updated site-specific incidence rates from 51 selected
      registries. Over the last decade, the annual percent change (APC) in mortality
      rate was around -3, -4% for the major European countries. The APC were similar
      for the Republic of Korea (APC = -4.3%), Australia (-3.7%), the USA (-3.6%),
      Japan (-3.5%), Ukraine (-3%) and the Russian Federation (-2.8%). In Latin
      America, the decline was less marked, but constant with APC around -1.6% in Chile
      and Brazil, -2.3% in Argentina and Mexico and -2.6% in Colombia. Cancers in the
      fundus and pylorus are more common in high incidence and mortality areas and have
      been declining more than cardia gastric cancer. Steady downward trends persist in
      gastric cancer mortality worldwide even in middle aged population, and hence
      further appreciable declines are likely in the near future.

PMID- 19382181
TI  - Genetic variation in D7S1875 repeat polymorphism of leptin gene is associated
      with increased risk for depression: a case-control study from India.
AB  - BACKGROUND: Epidemiologic data suggest an association between obesity and
      depression, however findings vary considerably across different studies. Both
      depression and obesity are disabling disorders associated with loss over appetite
      control, influenced by genetic and environmental factors and are risk factors for
      diseases like hypertension, cardiovascular disorders, etc. This study attempts to
      establish a link between the symptoms of depression, metabolic disorders, and
      obesity, to unravel the underlying association/s. METHODS: This exploratory case
      control study comprises 133 clinically diagnosed depressed individuals and 136
      age matched controls. DNA from all 269 subjects was genotyped for D7S1875 repeat
      polymorphism in the promoter region of Leptin (LEP) gene using polymerase chain
      reaction. RESULTS: Frequency of the shorter allele of D7S1875 (<208 bp) was 0.73
      in the depressive group versus 0.67 in the control group (P=.01). Cases
      homozygous for D7S1875> or =208 bp alleles had significantly higher value of
      systolic (130 versus 122; P<.009) and diastolic (85.4 versus 81; P=.01) blood
      pressure (SBP and DBP) than the individuals homozygous for<208 bp allele. A
      similar trend was observed for SBP (127.8 versus 123.6; P=.03) among controls
      homozygous for the longer or the shorter allele. Thus, the LEP gene appears to be
      an important genetic determinant for susceptibility to depression in the Indian
      population (OR=1.4913, 95% CI=1.0334-2.1522; P=.04). CONCLUSIONS: Our findings
      suggest that LEP gene variants could be related to depression and associated co
      morbidities such as hypertension.

PMID- 19382180
TI  - Downregulation of connective tissue growth factor by three-dimensional matrix
      enhances ovarian carcinoma cell invasion.
AB  - Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic
      malignancies, due mainly to the prevalence of undetected metastatic disease. The
      process of cell invasion during intraperitoneal anchoring of metastatic lesions
      requires concerted regulation of many processes, including modulation of adhesion
      to the extracellular matrix and localized invasion. Exploratory cDNA microarray
      analysis of early response genes (altered after 4 hr of 3D collagen culture)
      coupled with confirmatory real-time reverse-transcriptase polymerase chain
      reaction, multiple 3D cell culture matrices, Western blot, immunostaining,
      adhesion, migration and invasion assays were used to identify modulators of
      adhesion pertinent to EOC progression and metastasis. cDNA microarray analysis
      indicated a dramatic downregulation of connective tissue growth factor (CTGF) in
      EOC cells placed in invasion- mimicking conditions (3D Type I collagen).
      Examination of human EOC specimens revealed that CTGF expression was absent in
      46% of the tested samples (n = 41), but was present in 100% of normal ovarian
      epithelium samples (n = 7). Reduced CTGF expression occurs in many types of cells
      and may be a general phenomenon displayed by cells encountering a 3D environment.
      CTGF levels were inversely correlated with invasion such that downregulation of
      CTGF increased, while its upregulation reduced collagen invasion. Cells adhered
      preferentially to a surface comprised of both collagen I and CTGF relative to
      either component alone using alpha6beta1 and alpha3beta1 integrins. Together
      these data suggest that downregulation of CTGF in EOC cells may be important for
      cell invasion through modulation of cell-matrix adhesion.

PMID- 19382182
TI  - Material properties are related to stress fracture callus and porosity of
      cortical bone tissue at affected and unaffected sites.
AB  - Stress fractures are overuse injuries of bone that affect elite athletes and
      military recruits. One response of cortical bone to stress fracture is to lay
      down periosteal callus. The objectives of this study were to determine if
      material properties are different among bones with different stages of stress
      fracture callus, at both a callus site and at a distal site. Cortical specimens
      were mechanically tested to determine their stress-strain response. Material
      property differences were examined using nonparametric and regression analyses.
      At the callus site, material properties were low during the earliest stages of
      callus, higher with increasing callus maturity, but dropped at the late stage of
      callus. At the distal site, the material properties were low during early stages
      of callus and approached, or returned to, those of bones without callus during
      the late stages of callus. The effects of stress fracture and bone callus are not
      limited to the focal site of stress fracture.

PMID- 19382183
TI  - Sociodemographic, clinical, and treatment characteristics associated with
      worsened depression during treatment with citalopram: results of the NIMH
      STAR(*)D trial.
AB  - CONTEXT: Outcomes of antidepressant medication treatment for major depressive
      disorder include remission, response, and nonresponse. But nonresponse can
      include depression that worsened over the course of treatment, an outcome that
      has received scant attention. OBJECTIVE: To describe baseline sociodemographic,
      clinical, and treatment characteristics associated with worsened depression
      during a trial of citalopram. DESIGN, PARTICIPANTS, AND SETTINGS: Open-label
      clinical trial of 2,876 adult outpatients seen in 18 primary and 23 psychiatric
      care settings. INTERVENTION: Citalopram was delivered using measurement-based
      care and flexible dosing with the aim of achieving symptom remission. Symptom and
      side effect ratings were obtained at each treatment visit. MAIN OUTCOME MEASURES:
      Worsened depression was defined as an exit score >or=3 points above the
      pretreatment (baseline) score on the 16-item QIDS-SR. Baseline sociodemographic,
      clinical, and treatment characteristics were examined for association with
      worsened depression. RESULTS: Of 2,864 outpatients who returned for >or=2 post
      baseline visits, 150 (5.2%) had worsened depression at study exit. Baseline
      characteristics independently associated with increased worsened depression
      included African-American race (OR=2.02), having less than a college education
      (OR=2.36), posttraumatic stress disorder (OR=1.78), drug abuse (OR=1.97),
      hypochondriasis (OR=2.74). Participants with worsened depression spent less time
      in treatment; had fewer treatment visits; exited the study sooner; had more
      frequent, intense, and burdensome adverse effects; and were more intolerant of
      medication. CONCLUSIONS: The presence of certain baseline characteristics
      indicated a greater likelihood of worsened depression during antidepressant
      treatment. Patients with these characteristics should be monitored closely during
      treatment and may be candidates for more aggressive treatment.

PMID- 19382184
TI  - Formation of cartilage repair tissue in articular cartilage defects pretreated
      with microfracture and covered with cell-free polymer-based implants.
AB  - The aim of our study was to evaluate the mid-term outcome of a cell-free polymer
      based cartilage repair approach in a sheep cartilage defect model in comparison
      to microfracture treatment. Cell-free, freeze-dried implants (chondrotissue) made
      of a poly-glycolic acid (PGA) scaffold and hyaluronan were immersed in autologous
      serum and used for covering microfractured full-thickness articular cartilage
      defects of the sheep (n = 4). Defects treated with microfracture only served as
      controls (n = 4). Six months after implantation, cartilage implants and controls
      were analyzed by immunohistochemical staining of type II collagen, histological
      staining of proteoglycans, and histological scoring. Histological analysis showed
      the formation of a cartilaginous repair tissue rich in proteoglycans.
      Histological scoring documented significant improvement of repair tissue
      formation when the defects were covered with the cell-free implant, compared to
      controls treated with microfracture. Immunohistochemistry showed that the cell
      free implant induced cartilaginous repair tissue and type II collagen. Controls
      treated with microfracture showed marginal formation of a mixed-type repair
      tissue consisting of cartilaginous tissue and fibro-cartilage. Covering of
      microfractured defects with the cell-free polymer-based cartilage implant is
      suggested to be a promising treatment option for cartilage defects and improves
      the regeneration of articular cartilage.

PMID- 19382185
TI  - Polycyclic aromatic hydrocarbons from diesel emissions exert proallergic effects
      in birch pollen allergic individuals through enhanced mediator release from
      basophils.
AB  - BACKGROUND: Diesel exhaust particles (DEPs) act as adjuvants in the immune system
      and contribute to the increased prevalence and morbidity of asthma and allergic
      rhinitis. Polycyclic aromatic hydrocarbons (PAHs) are major components of DEPs,
      which may be involved in the induction and enhancement of proallergic processes.
      In this study we explored adjuvant effects of DEP-PAHs on activation parameters
      of human basophils, fostering allergic inflammation through the release of
      preformed or granule-derived mediators. METHODS: Heparinized blood samples from
      birch pollen allergic and control donors were stimulated with Bet v 1, the major
      allergen of birch pollen grains, alone or together with a mixture of 16
      environmental prominent PAHs (EPA-PAH standard). Flow cytometric analysis was
      performed for quantitative determination of PAH-enhanced basophil activation. To
      assess direct PAH effects on basophils, enriched cultures from both donor groups
      were exposed to benzo[a]pyrene (B[a]P) or phenanthrene (Phe), two major DEP-PAHs,
      with and without allergen. Supernatants were assayed for IL-4 and IL-8 secretion
      and histamine release by means of ELISA. RESULTS: At environmental relevant
      exposure levels EPA-PAH standard synergized with antigen and significantly
      enhanced basophil activation of all birch pollen allergic individuals up to 95%.
      Single PAHs significantly drove IL-8 secretion from sensitized basophils of all
      patients tested, and there was no further enhancement by addition of rBet v 1.
      B[a]P and Phe also significantly induced IL-4 secretion, a key factor for Th2
      development, from purified sensitized basophils in the absence of antigen
      suggesting an adjuvant role of DEP-PAHs in allergic sensitization. None of the
      basophil samples from healthy controls showed any PAH effect on mediator release.
      CONCLUSION: DEP-PAHs exert proallergic effects on sensitized basophils in an
      allergen independent fashion, suggesting a potential role of these pollutants for
      the allergic breakthrough in atopic individuals, who have not developed an
      allergic disease yet.

PMID- 19382186
TI  - Descriptive and mechanistic toxicity of conazole fungicides using the model test
      alga Dunaliella tertiolecta (Chlorophyceae).
AB  - Conazole fungicides are commonly used to prevent fungal growth on turf grass and
      agricultural crops. As many of these sites are adjacent to coastal waterways and
      estuaries, there exists the potential for nontarget effects of runoff on marine
      organisms. This study reports 96 h EC(50) values for four selected conazole
      fungicides (triadimefon = 5.98 mg/L; triadimenol = 5.51 mg/L; propiconazole =
      2.33 mg/L; hexaconazole = 0.91 mg/L) to the model test alga Dunaliella
      tertiolecta. We further investigated possible mechanisms of toxicity by examining
      sublethal effects of exposure on cell morphology, osmoregulatory function, and
      lipid composition. These mechanistic studies revealed that conazole exposure does
      not inhibit synthesis of the cell's glycerol osmolyte, but does result in an
      overall increase in cellular volume and total lipid content. Both fungi and
      chlorophytes rely on ergosterol to maintain membrane structure and fluidity, and
      we provide evidence that the sterol-inhibiting conazoles may interfere with
      ergosterol biosynthesis in the cell membrane of Dunaliella. These findings
      suggest that green algae may be especially susceptible to nontarget effects of
      sterol-inhibiting fungicides in marine systems.

PMID- 19382187
TI  - Osteosarcoma of the jaw/craniofacial region: outcomes after multimodality
      treatment.
AB  - BACKGROUND: The current study was performed to evaluate outcomes in patients with
      osteosarcoma of the head and neck (OHN) who were treated with surgery with or
      without radiotherapy (RT). METHODS: Between 1960 and 2007, 119 patients with OHN
      underwent macroscopic total resection with or without RT. The median age of the
      patients was 33 years (range, 7-77 years). Of these 119 patients 92 (77%)
      underwent surgery alone whereas 27 (23%) patients were treated with combined
      modality treatment (CMT) comprised of surgery and RT (median dose, 60 Gray [Gy];
      range, 50-66 Gy). RESULTS: The median follow-up was 5.8 years. Overall survival
      (OS) rates at 5 years and 10 years were 63% and 55%, respectively. Corresponding
      disease-specific survival (DSS) rates were 67% and 61%, respectively. Stratified
      analysis by resection margin status demonstrated that CMT compared with surgery
      alone improved OS (80% vs 31%; P = .02) and DSS (80% vs 35%; P = .02) for
      patients with positive/uncertain resection margins. Multivariate analysis
      indicated that CMT for patients with positive/uncertain resection margins
      improved OS (P < .0001). A total of 44 (37%) patients experienced local disease
      recurrence (LR) and 25 (21%) developed distant metastases (DM). There was no
      difference noted with regard to DSS if disease recurrence was isolated (LR vs DM:
      26% vs 29%, respectively, at 5 years; P = .48) The use of CMT versus surgery
      alone improved local control (LC) (75% vs 24%; P = .006) for patients with
      positive/uncertain resection margins. The rate of surgical complications was 28%
      at 5 years. The rates of RT-associated complications were 40% and 47% at 5 years
      and 10 years, respectively. CONCLUSIONS: The results of the current study
      indicated that RT in addition to surgery improves OS, DSS, and LC for patients
      with OHN who have positive/uncertain resection margins.

PMID- 19382190
TI  - When medical evidence alone is simply not enough.

PMID- 19382192
TI  - CD44 deficiency improves healing tendon mechanics and increases matrix and
      cytokine expression in a mouse patellar tendon injury model.
AB  - CD44 plays an important role in inflammation and healing. Previous studies
      investigated its role in inflammatory diseases and skin wounds; however, the role
      of CD44 in tendon healing is unknown. Therefore, we investigated the effect of
      CD44 in the healing of the patellar tendon in a knockout mouse model. We
      hypothesized that in comparison to wild-type counterparts, CD44 knockout mice
      would have decreased material parameters, increased organization, decreased
      expression of proinflammatory cytokines, and increased expression of matrix
      components during healing. These hypotheses were tested through an in vivo
      surgical model and mechanical, organizational, and gene expression analyses.
      Material strength and tissue organization were significantly improved in the CD44
      knockout mouse. This could be attributed to increased expression of cytokines and
      matrix components that are also elevated in regenerative healing. Our study
      showed that the absence of CD44 in a mouse patellar tendon injury creates an
      environment that is conducive to regenerative healing through altered gene
      expression, resulting in superior material properties and reduced cross-sectional
      area. Therefore, limiting the role of CD44 may improve healing parameters in
      adult tendon injury.

PMID- 19382193
TI  - The effect of rapamycin on bone growth in rabbits.
AB  - mTOR is a nutrient-sensing protein kinase that regulates numerous cellular
      processes. Our prior studies using the mTOR inhibitor, rapamycin, indicate an
      important role for mTOR in chondrogenesis. We extended our observations to a
      physiological, in vivo model of bone growth, direct infusion of rapamycin into
      the proximal tibial growth plates of rabbits. Rapamycin or DMSO vehicle was
      infused directly into growth plates by an osmotic minipump for 8 weeks. Tibial
      growth was followed radiographically. At the end of the experiment, growth plates
      were recovered for histological analysis. Six animals were studied. No untoward
      effects of rapamycin infusion were found. Bone growth of limbs exposed to
      rapamycin was slower than control limbs, particularly during the period of most
      rapid growth. Histological analysis revealed that growth plate height in the
      rapamycin-infused limbs was reduced. Both the hypertrophic and proliferative
      zones were significantly smaller in the rapamycin-infused limbs. Direct infusion
      of rapamycin into proximal tibial growth plates decreased the size of the growth
      plate and inhibited overall long bone growth. Rapamycin appears to affect both
      the proliferative and hypertrophic zones of the tibial growth plate. Our results
      indicate that nutrients may exert a direct effect on long bone growth via mTOR
      mediated modulation of chondrogenesis at the growth plate. and suggest that the
      possible inhibitory effects of rapamycin on skeletal growth warrant further
      attention before its use in children.

PMID- 19382194
TI  - Does loading influence the severity of cartilage degeneration in the canine
      Groove-model of OA?
AB  - Many animal models are used to study osteoarthritis (OA). In these models the
      role of joint loading in the development of OA is not fully understood. We
      studied the effect of loading on the development of OA in the canine Groove
      model. In ten female beagle dogs OA was induced in one knee according to the
      Groove-model. The animals were divided in groups with and without forced-loading.
      Forced-loading was achieved by fixing the contra-lateral limb to the trunk 3
      times a week for 4 hours. After 20 weeks joint tissues of all dogs were
      evaluated. Subjective evaluation revealed less movement with more loading in the
      forced-loading-group compared to the group without forced-loading. In both groups
      induction of OA resulted in macroscopical and microscopical OA changes as well as
      alterations in cartilage metabolism characteristics for OA. Although differences
      were small, for some parameters they were statistically significant for the
      forced-loading-group. There were no differences between the contra-lateral
      healthy joints of both groups. The present study demonstrates that in the Groove
      model intensified loading is not a prerequisite for the development of OA,
      although it adds to some extent to the severity of the OA.

PMID- 19382195
TI  - Cellular composition of the initial fracture hematoma compared to a muscle
      hematoma: a study in sheep.
AB  - Bone fracture leads to a cycle of inflammation, cellular migration, and
      proliferation to restore tissue integrity. Immune cells at the site of injury are
      involved especially in the early phase of the healing process, but little is
      known about the cells present in the initial fracture hematoma. The hypothesis of
      this study was that the cellular composition in a fracture hematoma differs from
      that found in a muscle hematoma and that these divergences get more pronounced
      over time. By using a reproducible osteotomy model and muscle trauma in sheep the
      distributions of the immune cell subpopulations were evaluated 1 and 4 h after
      surgery. The cell amount within the first 4 h increased in both hematoma. The
      number of dead cells was higher in the muscle hematoma. One hour postoperatively
      the initial fracture hematoma revealed a lower granulocyte percentage compared to
      the muscle hematoma. The ratio of T helper to cytotoxic T cells was higher in the
      fracture hematoma compared to the muscle hematoma at both investigated time
      points. B cell percentage increased in the fracture but not in the muscle
      hematoma from 1 to 4 h. This is the first study that compares the immune cell
      subpopulations of a fracture and muscle hematoma.

PMID- 19382196
TI  - Flow cytometric evaluation of CD38 expression assists in distinguishing
      follicular hyperplasia from follicular lymphoma.
AB  - The distinction of follicular lymphoma (FL) from reactive follicular hyperplasia
      (FH) can be a diagnostic challenge in flow cytometry. In this study, the median
      fluorescent intensity (MFI) of CD38 as assessed by flow cytometry on B and T cell
      subpopulations in 102 lymph nodes specimens with histopathologically confirmed FL
      was compared with 55 cases of FH. The MFI of CD38 was highly significantly
      reduced in the neoplastic B cells in FL when compared with the reactive germinal
      center B cells in FH (P < 1.0E-16). The MFI of CD38 did not differ between the
      non-neoplastic B-cells in FL and nongerminal center B-cells in FH (P = 0.14) or
      between T-cells and non-neoplastic B-cells in FL (P = 0.63). A marginal increase
      in the MFI of CD38 was seen for T cells in FL compared with FH (P = 0.04). An
      increased difference in the MFI of CD38 was identified for T-cells compared with
      nongerminal center B-cells in FH (P = 0.005). No difference in CD38 expression
      was seen between Grades 1, 2, or 3 FL. The study also confirmed increased
      expression of CD10 (P < 1.0E-9), decreased CD19 (P < 1.0E-22), and CD20 (P < 1.0E
      16) in FL in comparison with FH, as has been previously reported. This study
      identified decreased CD38 as a common finding in FL in comparison with FH and
      provides an additional tool to help differentiate FL from FH by flow cytometry.

PMID- 19382197
TI  - CD22 expression on blastic plasmacytoid dendritic cell neoplasms and reactivity
      of anti-CD22 antibodies to peripheral blood dendritic cells.
AB  - We identified CD22 expression on a blastic plasmacytoid dendritic cell (pDC)
      neoplasm presenting as a leukemia in a child. CD22 expression, as determined by
      the antibody s-HCL-1, was also noted on the neoplastic cells from three
      additional patients with blastic pDC tumors identified at our institution.
      Subsequently we determined that peripheral blood pDCs react with the s-HCL-1
      antibody demonstrating that normal pDCs express CD22. Evaluation of five
      additional anti-CD22 antibodies indicated that staining of pDCs with these
      reagents was poor except for s-HCL-1. Therefore, the detection of CD22 on pDCs is
      best demonstrated with the use of this specific antibody clone. All anti-CD22
      antibodies stained conventional DCs. We also evaluated the reactivity of the anti
      CD22 antibodies with basophils and noted that the pattern of staining was similar
      to that seen with pDCs. The studies demonstrate that normal DCs and pDC neoplasms
      express CD22, and highlight clone specific differences in anti-CD22 antibody
      reactivity patterns on pDCs and basophils.

PMID- 19382198
TI  - Myofibrillogenesis in skeletal muscle cells in zebrafish.
AB  - The "premyofibril" model of myofibrillogenesis, based on observations in cultured
      avian muscle cells, proposes that mature myofibrils are preceded by two
      intermediary structures: premyofibrils and nascent myofibrils. To determine if
      this model applies to zebrafish skeletal muscle development, we stained
      developing embryos with antibodies to sarcomeric alpha-actinin and myosin II. In
      the youngest muscle cells, sarcomeric alpha-actinin and non-muscle myosin II were
      each localized in linear arrays of small bands that resembled the premyofibrils
      in avian myocytes. The distribution of muscle-specific myosin II began as
      scattered short filaments followed in time by overlapping bundles of filaments
      and organized A-bands in the older somites. Alpha-actinin organization changed
      from small z-bodies to beaded Z-bands and ordered Z-bands in myofibrils that
      extended the length of the elongating somites. In older somites with mature
      myofibrils, premyofibrils were also present at the ends of the mature myofibrils,
      suggesting that as the cells and somites grew longer, premyofibrils were involved
      in the elongation of existing mature myofibrils. Fluorescence Recovery After
      Photobleaching showed that the exchange of proteins (actin, alpha-actinin, FATZ,
      myotilin and telethonin) between sarcoplasm and the Z-bands of mature myofibrils
      in zebrafish resembled that seen for the same proteins in cultured avian
      myotubes, suggesting that myofibril assembly and maintenance in zebrafish share
      common properties with avian muscle. Cell Motil. Cytoskeleton 2009. (c) 2009
      Wiley-Liss, Inc.

PMID- 19382199
TI  - HA-tagging of putative flagellar proteins in Chlamydomonas reinhardtii identifies
      a novel protein of intraflagellar transport complex B.
AB  - Proteomic analysis of flagella from the green alga Chlamydomonas reinhardtii has
      identified over 600 putative flagellar proteins. The genes encoding nine of these
      not previously characterized plus the previously described PACRG protein were
      cloned, inserted into a vector adding a triple-HA tag to the C-terminus of the
      gene product, and transformed into C. reinhardtii. Expression was confirmed by
      western blotting. Indirect immunofluorescence located all 10 fusion proteins in
      the flagellum; PACRG was localized to a subset of outer doublet microtubules. For
      some proteins, additional signal was observed in the cell body. Among the latter
      was FAP232-HA, which showed a spotted distribution along the flagella and an
      accumulation at the basal bodies. This pattern is characteristic for
      intraflagellar transport (IFT) proteins. FAP232-HA co-localized with the IFT
      protein IFT46 and co-sedimented with IFT particles in sucrose gradients.
      Furthermore, it co-immunoprecipitated with IFT complex B protein IFT46, but not
      with IFT complex A protein IFT139. We conclude that FAP232 is a novel component
      of IFT complex B and rename it IFT25. Homologues of IFT25 are encoded in the
      genomes of a subset of organisms that assemble cilia or flagella; C. reinhardtii
      IFT25 is 37% identical to the corresponding human protein. Genes encoding IFT25
      homologues are absent from the genomes of organisms that lack cilia and flagella
      and, interestingly, also from those of Drosophila melanogaster and Caenorhabditis
      elegans, suggesting that IFT25 has a specialized role in IFT that is not required
      for the assembly of cilia or flagella in the worm and fly. Cell Motil.
      Cytoskeleton 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19382200
TI  - Comparing safety and efficacy of first-line irinotecan/fluoropyrimidine
      combinations in elderly versus nonelderly patients with metastatic colorectal
      cancer: findings from the bolus, infusional, or capecitabine with camptostar
      celecoxib study.
AB  - BACKGROUND: Irinotecan-based chemotherapy regimens are 1 option for treatment of
      metastatic colorectal cancer (mCRC). The authors report the safety and efficacy
      of such regimens in elderly patients using a large phase III trial (bolus,
      infusional, or capecitabine with camptostar-celecoxib [BICC-C]) cohort. METHODS:
      In period 1, 430 previously untreated patients with mCRC were randomized in a 3
      by-2 design to receive irinotecan plus infusional 5-fluorouracil, and leucovorin
      (FOLFIRI), irinotecan plus bolus 5-fluorouracil/leucovorin (mIFL), and irinotecan
      plus oral capecitabine (CapeIRI). In period 2, an additional 117 patients were
      randomized to receive FOLFIRI or mIFL and bevacizumab. In both periods patients
      were also randomized to a double-blind treatment with celecoxib or placebo. A
      secondary analysis was conducted examining the safety and efficacy of these
      regimens in elderly (age >70 years) versus nonelderly (age <or=70 years)
      patients. RESULTS: In period 1, 19.5% of patients were elderly, compared with
      24.8% in period 2. Rates of grade 3 and higher toxicity did not differ
      significantly between age groups in either period by treatment arm, with the
      exception of asthenia in the FOLFIRI and CapeIRI arms (P = .05 and P = .03,
      respectively) and dehydration in the CapeIRI arm in period 1 (P = .02). Overall
      progression-free survival for FOLFIRI in both periods was not statistically
      different by age. Objective responses and overall survival did not differ by
      patient age within treatment arms and periods. CONCLUSIONS:
      Irinotecan/fluoropyrimidine combinations are well tolerated in the elderly
      population, with similar efficacy to that found in nonelderly patients in first
      line mCRC.

PMID- 19382201
TI  - Association of the progesterone receptor gene with endometrial cancer risk in a
      Chinese population.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) in the progesterone receptor
      (PGR) gene have been associated with the risk of endometrial cancer. However, to
      the authors' knowledge, no study to date has systematically evaluated the role of
      the PGR gene in endometrial carcinogenesis. METHODS: Exposure information and DNA
      samples collected in the Shanghai Endometrial Cancer Study, a population-based
      case-control study of 1,204 incident cases and 1,212 age- and frequency-matched
      population controls, were used in this study. Seven tag SNPs were identified for
      the PGR gene plus the 5-kilobase (kb) flanking regions using the Han Chinese data
      from the HapMap project with a pairwise correlation coefficient (r(2)) >or= 0.90.
      These 7 SNPs captured 92% of SNPs in the region with a pairwise r(2) >or= 0.90 or
      100% of SNPs with a pairwise r(2) >or= 0.80. Genotyping of polymorphisms was
      performed by using the Affymetrix MegAllele Targeted Genotyping System. A
      logistic regression model was used to compute adjusted odds ratios (ORs) and 95%
      confidence intervals (95% CIs). RESULTS: Of 7 tag SNPs that were assessed, 2
      polymorphisms in the 3' flanking region of the PGR gene, reference SNP
      identification number (rs) 11224561 (rs11224561) and rs471767, were associated
      with the risk of endometrial cancer. The cytosine/cytosine (CC) genotype of SNP
      rs11224561 was associated with decreased risk (OR, 0.68; 95% CI, 0.50-0.92)
      compared with the thymine/thymine (TT) genotype. Carrying the guanine (G) allele
      of the rs471767 SNP also was associated with decreased risk, although the
      association was not statistically significant (OR, 0.78, 95%CI, 0.59-1.04 and OR,
      0.32, 95%CI, 0.03-3.05 for the adenine [A]G and GG genotypes, respectively,
      compared with the homozygote AA). CONCLUSIONS: The current findings suggested
      that polymorphisms in the 3' flanking region of the PGR gene may be associated
      with the risk of endometrial cancer.

PMID- 19382202
TI  - Actinic keratoses: Natural history and risk of malignant transformation in the
      Veterans Affairs Topical Tretinoin Chemoprevention Trial.
AB  - BACKGROUND: Actinic keratoses (AKs) are established as direct precursors of
      squamous cell carcinoma (SCC), but there is significant controversy regarding the
      rate at which AKs progress to SCC. The authors of this report studied a high-risk
      population to estimate the risk of progression of AK to SCC and to basal cell
      carcinoma (BCC) and the risk of spontaneous regression of untreated AKs. METHODS:
      Data were obtained from participants in the Department of Veterans Affairs
      Topical Tretinoin Chemoprevention Trial. Participants were examined every 6
      months for up to 6 years. At each examination, the locations on the face and ears
      of clinically diagnosed AKs and lesions scheduled for biopsy were marked, and
      high-resolution digital photographs were taken. These photographs were used later
      to map and track the presence, absence, or biopsy of each AK across visits.
      RESULTS: In total, 7784 AKs were identified on the face and ears of 169
      participants. The risk of progression of AK to primary SCC (invasive or in situ)
      was 0.60% at 1 year and 2.57% at 4 years. Approximately 65% of all primary SCCs
      and 36% of all primary BCCs diagnosed in the study cohort arose in lesions that
      previously were diagnosed clinically as AKs. The majority of AKs (55%) that were
      followed clinically were not present at the 1-year follow-up, and the majority
      (70%) were not present at the 5-year follow-up. CONCLUSIONS: In the current
      study, the authors quantified the malignant potential of clinically diagnosed AKs
      for both SCC and BCC, although many did not persist, and the results suggested
      that AKs may play a greater role in the overall burden of keratinocyte carcinomas
      than previously documented.

PMID- 19382203
TI  - Clinical features and prognostic factors in patients with bone metastases from
      hepatocellular carcinoma receiving external beam radiotherapy.
AB  - BACKGROUND: The current study was performed to identify clinical features and
      independent predictors of survival in patients with bone metastases from
      hepatocellular carcinoma (HCC). METHODS: Patients (n = 205) with bone metastases
      from HCC received external beam radiotherapy (EBRT) between 1997 and 2007.
      Demographic variables, laboratory values, tumor characteristics, and treatment
      modalities were determined before EBRT. The total radiation dose ranged from 32
      to 66 grays (Gy) (median, 50 Gy) and was focused on the involved bone. RESULTS:
      In 80 of 205 (39.0%) patients with bone metastasis from HCC, tumors were
      characterized by osteolytic, expansile soft-tissue masses. Overall pain relief
      from EBRT occurred in 204 patients (99.5%). No consistent dose-response relation
      was found for palliation of bone metastases with doses between 32 and 66 Gy (P =
      .068), but the retreatment rate was higher in patients with expansile soft
      tissue. On univariate analysis, shorter survival was associated with poorer
      Karnofsky performance status (KPS), higher gamma-glutamyltransferase and alpha
      fetoprotein levels, tumor size >5 cm, uncontrolled intrahepatic tumors,
      multifocal bone lesions, involvement of spinal vertebrae, extraosseous
      metastases, and a shorter disease-free interval after an initial diagnosis of
      HCC. On multivariate analysis, pretreatment-unfavorable predictors were
      associated with lower KPS, higher tumor markers, and uncontrolled intrahepatic
      tumor when KPS was considered. The median survival was 7.4 months. CONCLUSIONS:
      The results of the current study provide detailed information regarding clinical
      features, survival outcomes, and prognostic factors for HCC with bone metastases
      in a relatively large cohort of patients treated with EBRT. These prognostic
      factors will help in determining which dose and fraction are appropriate.

PMID- 19382205
TI  - Structure of a pullulanase from Bacillus acidopullulyticus.

PMID- 19382204
TI  - Automated site preparation in physics-based rescoring of receptor ligand
      complexes.
AB  - Hydrogen atoms are not typically observable in X-ray crystal structures, but
      inferring their locations is often important in structure-based drug design. In
      addition, protonation states of the protein can change in response to ligand
      binding, as can the orientations of OH groups, a subtle form of "induced fit." We
      implement and evaluate an automated procedure for optimizing polar hydrogens in
      protein-binding sites in complex with ligands. Specifically, we apply the
      previously described Independent Cluster Decomposition Algorithm (ICDA) algorithm
      (Li et al., Proteins 2007;66:824-837), which assigns the ionization states of
      titratable residues, the amide orientations of Asn/Gln side chains, the imidazole
      ring orientation in His, and the orientations of OH/SH groups, in a unified
      algorithm. We test the utility of this method for identifying nativelike ligand
      poses using 247 protein-ligand complexes from an established database of docked
      decoys. Pose selection is performed with a physics-based scoring function based
      on a molecular mechanics energy function and a Generalized Born implicit solvent
      model. The use of the ICDA receptor preparation protocol, implemented with no
      knowledge of the native ligand pose, increases the accuracy of pose selection
      significantly, with the average RMSD over all complexes decreasing from 2.7 to
      1.5 A when applying ICDA. Large improvements are seen for specific classes of
      binding sites with titratable groups, such as aspartyl proteases.

PMID- 19382206
TI  - Crystal structure of Saccharomyces cerevisiae Ygr203w, a homolog of single-domain
      rhodanese and Cdc25 phosphatase catalytic domain.

PMID- 19382207
TI  - Overexpression of glycogen synthase kinase 3beta sensitizes neuronal cells to
      ethanol toxicity.
AB  - The developing central nervous system (CNS) is particularly susceptible to
      ethanol toxicity. The loss of neurons underlies many of the behavioral deficits
      observed in fetal alcohol spectrum disorders (FASD). The mechanisms of ethanol
      induced neuronal loss, however, remain incompletely elucidated. We demonstrated
      that glycogen synthase kinase 3beta (GSK3beta), a multifunctional
      serine/threonine kinase, was involved in ethanol neurotoxicity. The activity of
      GSK3beta is negatively regulated by its phosphorylation at serine 9 (Ser9).
      Ethanol induced dephosphorylation of GSK3beta at Ser9 and the activation of Bax
      as well as caspase-3 in the developing mouse brain. These ethanol-induced
      alterations were ameliorated by the pretreatment of a GSK3beta inhibitor,
      lithium. To determine the role of GSK3beta in ethanol neurotoxicity, we
      overexpressed wild-type (WT), S9A mutant or dominant-negative (DN) mutant
      GSK3beta in a neuronal cell line (SK-N-MC). Ethanol only modestly reduced the
      viability of parental SK-N-MC cells but drastically induced caspase-3 activation
      and apoptosis in cells overexpressing WT or S9A GSK3beta, indicating that the
      high levels of GSK3beta or the active form of GSK3beta increased cellular
      sensitivity to ethanol. Contrarily, overexpression of DN GSK3beta conferred
      resistance to ethanol toxicity. Lithium and other specific GSK3beta inhibitors
      abolished the hypersensitivity to ethanol caused by WT or S9A overexpression.
      Bax, a proapoptotic protein, is a substrate of GSK3beta. Cells overexpressing WT
      or S9A GSK3beta were much more sensitive to ethanol-induced Bax activation than
      parental SK-N-MC cells. Our results indicate that GSK3beta may be a mediator of
      ethanol neurotoxicity, and its expression status in a cell may determine ethanol
      vulnerability.

PMID- 19382208
TI  - Inhibitors of the mitochondrial permeability transition reduce ammonia-induced
      cell swelling in cultured astrocytes.
AB  - Ammonia is the principal neurotoxin implicated in the pathogenesis of hepatic
      encephalopathy, and astrocytes are the neural cells predominantly affected in
      this condition. Astrocyte swelling (cytotoxic edema) represents a critical
      component of the brain edema in acute form of hepatic encephalopathy (acute liver
      failure, ALF). Although mechanisms of astrocyte swelling by ammonia are not
      completely understood, cultured astrocytes exposed to pathophysiological levels
      of ammonia develop the mitochondrial permeability transition (mPT), a process
      that was shown to result in astrocyte swelling. Cyclosporin A (CsA), a
      traditional inhibitor of the mPT, was previously shown to completely block
      ammonia-induced astrocyte swelling in culture. However, the efficacy of CsA to
      protect cytotoxic brain edema in ALF is problematic because it poorly crosses the
      blood-brain barrier, which is relatively intact in ALF. We therefore examined the
      effect of agents that block the mPT but are also known to cross the blood-brain
      barrier, including pyruvate, magnesium, minocycline, and trifluoperazine on the
      ammonia-induced mPT, as well as cell swelling. Cultured astrocytes exposed to
      ammonia for 24 hr displayed the mPT as demonstrated by a CsA-sensitive
      dissipation of the mitochondrial inner membrane potential. Pyruvate, minocycline,
      magnesium, and trifluoperazine significantly blocked the ammonia-induced mPT.
      Ammonia resulted in a significant increase in cell volume, which was blocked by
      the above-mentioned agents to a variable degree. A regression analysis indicated
      a high correlation between the effectiveness of reducing the mPT and cell
      swelling. Our data suggest that all these agents have therapeutic potential in
      mitigating brain edema in ALF.

PMID- 19382209
TI  - Activated retinal glia promote neurite outgrowth of retinal ganglion cells via
      apolipoprotein E.
AB  - In the present study, we investigated the role and mechanism through which
      activated retinal glia stimulate retinal ganglion cell (RGC) neurite outgrowth.
      We have found that the level of retinal glial activation correlates directly with
      enhanced RGC neurite outgrowth after a preconditioning intravitreal Zymosan
      injection. Reduction in the number of activated glia in primary rat retinal
      cultures led to significantly reduced RGC neurite outgrowth. Glial-related
      neurite outgrowth appears to be, at least in part, mediated via apolipoprotein E
      (ApoE), which is expressed by activated retinal astrocytes and Muller glia. ApoE
      deficient mice showed significantly reduced RGC neurite outgrowth potential after
      intravitreal Zymosan injection compared with age-matched wild-type animals. These
      observations suggest that ApoE, expressed by activated retinal glia, stimulates
      RGC neurite outgrowth after intravitreal Zymosan injection.

PMID- 19382210
TI  - Neurocognitive and behavioral impact of sleep disordered breathing in children.
AB  - The consequences of poor quality and/or inadequate sleep in children and
      adolescents have become a major public health concern, and one in which pediatric
      health care professionals have become increasingly involved. In particular,
      insufficient and/or fragmented sleep resulting from primary sleep disorders such
      as obstructive sleep apnea (OSA), often compounded by the presence of comorbid
      sleep disorders as well as by voluntary sleep curtailment related to lifestyle
      and environmental factors, has been implicated in a host of negative
      consequences. These range from metabolic dysfunction and increased cardiovascular
      morbidity to impairments in mood and academic performance. The following review
      will focus on what is currently known about the effects of sleep disordered
      breathing (SDB) specifically on neurobehavioral and neurocognitive function in
      children. Because of the scarcity of literature on the cognitive and behavioral
      impact of sleep disorders in infants and very young children, this review will
      target largely the preschool/school-aged child and adolescent populations. In
      addition, the focus will be on a review of the most recent literature, as a
      supplement to several excellent previous reviews on the topic.

PMID- 19382211
TI  - Microglia processes block the spread of damage in the brain and require
      functional chloride channels.
AB  - Microglia cells exhibit two forms of motility, constant movement of filopodia
      probing surrounding brain tissue, and outgrowth of larger processes in response
      to nearby damage. The mechanisms and functions of filopodia sensing and process
      outgrowth are not well characterized but are likely critical for normal immune
      function in the brain. Using two photon laser scanning microscopy we investigated
      microglia process outgrowth in response to damage, and explored the relationship
      between process outgrowth and filopodia movement. Further, we examined the roles
      of Cl(-) or K(+) channel activation, as well as actin polymerization in these two
      distinct processes, because mechanistic understanding could provide a strategy to
      modulate microglia function. We found that volume sensitive Cl(-) channel
      blockers (NPPB, tamoxifen, DIDS) prevented the rapid process outgrowth of
      microglia observed in response to damage. In contrast, filopodia extension during
      sensing was resistant to Cl(-) channel inhibitors, indicating that these motile
      processes have different cellular mechanisms. However, both filopodia sensing and
      rapid process outgrowth were blocked by inhibition of actin polymerization.
      Following lesion formation under control conditions, rapidly outgrowing processes
      contacted the damaged area and this was associated with a 37% decrease in lesion
      volume. Inhibition of process outgrowth by Cl(-) channel block, prevention of
      actin polymerization, or by selectively ablating microglia all allowed lesion
      volume to increase and spread into the surrounding tissue. Therefore, process
      outgrowth in response to focal brain damage is beneficial by preventing lesion
      expansion and suggests microglia represent a front line defence against damage in
      the brain.

PMID- 19382212
TI  - Heterogeneity of Kir4.1 channel expression in glia revealed by mouse
      transgenesis.
AB  - The weakly inwardly rectifying K(+) channel Kir4.1 is found in many glial cells
      including astrocytes. However, questions remain regarding the relative
      contribution of Kir4.1 to the resting K(+) conductance of mature astrocytes in
      situ. We employed a bacterial artificial chromosome transgenic approach in mice
      to visualize Kir4.1 expression in vivo. These mice (Kir4.1-EGFP) express enhanced
      green fluorescent protein (EGFP) under the transcriptional control of the Kir4.1
      promoter. The brains of adult Kir4.1-EGFP transgenic mice showed co-expression of
      EGFP and Kir4.1 in astrocytes. In addition, weaker expression of EGFP was
      detected in NG2+ glial cells when compared with EGFP expression in GFAP+ glial
      cells. Whole-cell voltage clamp recordings of EGFP+ glial cells in the CA1 area
      of the adult mouse hippocampus indicated astrocytes displaying properties
      consistent with both the "passive" and "complex" subpopulations. EGFP+ cells with
      bright fluorescence had the linear current-voltage (I-V) relationships and
      extensive gap junctional coupling characteristic of passive astrocytes. However,
      EGFP+ glia with weaker fluorescence displayed properties associated with complex
      astrocytes including nonlinear I-V relationships and lack of intercellular gap
      junctional coupling. Pharmacological blockade of inward currents implied that
      Kir4.1 channels constitute the dominant resting K(+) conductance in both glial
      cell types and are more highly expressed in passive astrocytes. These results
      suggest differential expression of Kir4.1 in glia and that this channel likely
      underlies the resting K(+) conductance in passive and complex astrocytes.

PMID- 19382213
TI  - Development of functional LH Receptors on pig cumulus-oocyte complexes cultured
      in vitro by a novel two-step culture system.
AB  - We show in the present study that freshly isolated pig cumulus-oocyte complexes
      (COCs) display a limited response to LH, as assessed by the expression of
      hyaluronan synthase 2 (Has2) mRNA, activation of protein kinase A (PKA),
      production of hyaluronic acid (HA) and progesterone, cumulus cell expansion and
      resumption of meiosis. These data indicate that freshly isolated COCs do not
      possess a sufficient number of functional LH receptors (LHR). However, the
      expression of Lhr significantly increased during the culture of COCs in vitro in
      a medium supplemented with FSH. Assuming that the effect of FSH on LHR induction
      is mediated via cAMP signaling pathways, we developed a new culture system, in
      which the COCs were pre-cultured for 72 hr in a medium supplemented with dbcAMP.
      The pre-cultured COCs remained in the germinal vesicle stage, their cumulus
      investment underwent a dramatic increase in size and gap junctions between the
      cumulus cells were preserved. The stimulation of such COCs with either FSH or LH
      led to the resumption and completion of meiosis, activation of PKA, expression of
      Has2, synthesis of large amounts of HA and progesterone, and extensive expansion
      of cumulus cells. We conclude that the formation of functional LHR is stimulated
      in cumulus cells during the culture in vitro in a cAMP-dependent pathway. The
      dbcAMP-treated COCs thus represent a new model in which the resumption of meiosis
      and cumulus expansion can be induced exclusively by the action of recombinant LH.

PMID- 19382216
TI  - Omalizumab for treatment of ABPA exacerbations in CF patients.

PMID- 19382214
TI  - Insulin-like growth factor-I-stimulated Akt phosphorylation and oligodendrocyte
      progenitor cell survival require cholesterol-enriched membranes.
AB  - Previously we showed that insulin-like growth factor-I (IGF-I) promotes sustained
      phosphorylation of Akt in oligodendrocyte progenitor cells (OPCs) and that Akt
      phosphorylation is required for survival of these cells. The direct mechanisms,
      however, by which IGF-I promotes Akt phosphorylation are currently undefined.
      Recently, cholesterol-enriched membranes (CEMs) have been implicated in
      regulation of growth factor-mediated activation of the PI3K/Akt pathway and
      survival of mature oligodendrocytes; however, less is know about their role in
      OPC survival. In the present study, we investigate the role of CEMs in IGF-I
      mediated Akt phosphorylation and OPC survival. We report that acute disruption of
      membrane cholesterol with methyl-beta-cyclodextrin results in altered OPC
      morphology and inhibition of IGF-I-mediated Akt phosphorylation. We also report
      that long-term inhibition of cholesterol biosynthesis with 25-hydroxycholesterol
      blocks IGF-I stimulated Akt phosphorylation and cell survival. Moreover, we show
      that the PI3K regulatory subunit, p85, Akt, and the IGF-IR are sequestered within
      cholesterol-enriched fractions in steady-state stimulation of the IGF-IR and that
      phosphorylated Akt and IGF-IR are present in cholesterol-enriched fractions with
      IGF-I stimulation. Together, the results of these studies support a role for CEMs
      or "lipid rafts" in IGF-I-mediated Akt phosphorylation and provide a better
      understanding of the mechanisms by which IGF-I promotes OPC survival.

PMID- 19382218
TI  - Fluticasone propionate/salmeterol and exercise-induced asthma in children with
      persistent asthma.
AB  - RATIONALE: Exercise is a common trigger in children with persistent asthma and
      inhaled corticosteroids have been shown to effectively treat clinical
      manifestations of persistent asthma, including protection from decrements in lung
      function caused by exercise. The goal of this study was to evaluate the
      effectiveness of fluticasone propionate/salmeterol 100/50 mcg compared with
      fluticasone propionate 100 mcg for the prevention of airflow limitation triggered
      by standardized exercise challenge in pediatric and adolescent patients with
      persistent asthma. METHODS: Multicenter, randomized, double-blind, parallel group
      trial of 248 subjects with persistent asthma (age 4-17 years) randomized to
      receive fluticasone propionate/salmeterol (100/50 mcg twice daily) or fluticasone
      propionate alone (100 mcg twice daily) via Diskus for 4 weeks. Exercise challenge
      tests were performed during screening and approximately 8 hr after administration
      of the blinded study medication on Treatment Day 28. RESULTS: After 4 weeks of
      therapy both treatments provided protection following exercise challenge. The
      protection estimated by the maximal fall in FEV(1) was significantly better for
      fluticasone propionate/salmeterol (9.5 +/- 0.8% [mean +/- SE]) compared with
      fluticasone propionate alone (12.7 +/- 1.1%, P = 0.021). Statistically
      significant differences were not observed for asthma rescue-free days and asthma
      symptom-free days. CONCLUSION: Chronic dosing with fluticasone
      propionate/salmeterol in a single device provides superior protection compared
      with an inhaled corticosteroid alone in protecting against exercise-induced
      asthma in children with persistent asthma.

PMID- 19382217
TI  - Higher pulmonary dead space may predict prolonged mechanical ventilation after
      cardiac surgery.
AB  - Children undergoing congenital heart surgery are at risk for prolonged mechanical
      ventilation and length of hospital stay. We investigated the prognostic value of
      pulmonary dead space fraction as a non-invasive, physiologic marker in this
      population. In a prospective, cross-sectional study, we measured pulmonary dead
      space fraction in 52 intubated, pediatric patients within 24 hr postoperative
      from congenital heart surgery. Measurements were obtained with a bedside, non
      invasive cardiac output (NICO) monitor (Respironics Novametrix, Inc.,
      Wallingford, CT). Median pulmonary dead space fraction was 0.46 (25-75% IQR 0.34
      0.55). Pulmonary dead space fraction significantly correlated with duration of
      mechanical ventilation and length of hospital stay in the entire cohort (r(s) =
      0.51, P = 0.0002; r(s) = 0.51, P = 0.0002) and in the subset of patients without
      residual intracardiac shunting (r(s) = 0.45, P = 0.008; r(s) = 0.49, P = 0.004).
      In a multivariable logistic regression model, pulmonary dead space fraction
      remained an independent predictor for prolonged mechanical ventilation in the
      presence of cardiopulmonary bypass time and ratio of the partial pressure of
      arterial oxygen to the fraction of inspired oxygen (OR 2.2; 95% CI 1.14-4.38; P =
      0.02). The area under the receiver operator characteristic curve for this model
      was 0.91. Elevated pulmonary dead space fraction is associated with prolonged
      mechanical ventilation and hospital stay in pediatric patients who undergo
      surgery for congenital heart disease and has additive predictive value in
      identifying those at risk for longer duration of mechanical ventilation.
      Pulmonary dead space may be a useful prognostic tool for clinicians in patients
      who undergo congenital heart surgery.

PMID- 19382219
TI  - Predicting changes in clinical status of young asthmatics: clinical scores or
      objective parameters?
AB  - Preventing asthma exacerbation is an important goal of asthma management. The
      existing clinical tools are not good in predicting asthma exacerbations in young
      children. Childhood Asthma Control Test (C-ACT) was recently published to be a
      simple tool for assessing disease control in young children. This study
      investigated C-ACT and other disease-related factors for indicating longitudinal
      changes in asthma status and predicting asthma exacerbations. During the same
      clinic visit, asthma patients aged 4-11 years completed the Chinese version of C
      ACT and underwent exhaled nitric oxide and spirometric measurements. Blinded to
      these results, the same investigator assigned Disease Severity Score (DSS) and
      rated asthma control according to Global Initiative for Asthma. Asthma
      exacerbations during the next 6 months were recorded. Ninety-seven patients were
      recruited, with their mean (standard deviation [SD]) age being 9.2 (2.0) years.
      Thirty-six (37.1%) patients had uncontrolled asthma at baseline. C-ACT, DSS, and
      FEV(1) differed among patients with different control status (P < 0.001 for C-ACT
      and DSS; P = 0.028 for FEV(1)). Thirty-two patients had asthma exacerbations
      during the 6-month follow-up. Changes in patients' C-ACT scores correlated with
      changes in asthma control status, DSS, and FEV(1) (P = 0.019, 0.034, and 0.020,
      respectively). C-ACT score was lower among patients with asthma exacerbations
      (mean [SD]: 22.9 [4.2] vs. 24.5 [2.1]; P = 0.015). Logistic regression confirmed
      that the occurrence of asthma exacerbations was associated only with baseline C
      ACT (B = -0.203, P = 0.042). In conclusion, C-ACT is better than DSS and
      objective parameters in reflecting changes in asthma status and predicting asthma
      exacerbations in young children.

PMID- 19382220
TI  - Early oxygen uptake recovery following exercise testing in children with chronic
      chest diseases.
AB  - The value of exercise testing as an objective measure of disease severity in
      patients with chronic chest diseases (CCD) is becoming increasingly recognized.
      The aim of this study was to investigate changes in oxygen uptake (VO2) during
      early recovery following maximal cardiopulmonary exercise testing (CPXT) in
      relation to functional capacity and markers of disease severity. Twenty-seven
      children with CCD (age 12.7 +/- 3.1 years; 17 female) [19 children with Cystic
      fibrosis (CF) (age 13.4 +/- 3.1 years; 10 female) and 8 with other stable non-CF
      chest diseases (NON-CF) (age 11.1 +/- 2.2 years; 7 female)] and 27 healthy
      controls (age 13.2 +/- 3.3 years; 17 female) underwent CPXT on a cycle ergometer.
      On-line respiratory gas analysis measured VO2 before and during CPXT to peak VO2)
      (VO2(peak)), and during the first 10 min of recovery. Early VO2 recovery was
      quantified by the time (sec) to reach 50% of the VO2 (peak) value. Early VO2
      recovery was correlated against spirometry [forced expiratory volume in 1 sec
      (FEV(1)) and forced expiratory flow between 25% and 75% of the forced vital
      capacity (FEF(25-75))] and aerobic fitness (VO2)(peak)) as a measure of
      functional capacity. Disease severity was graded in the CF patients by the
      Shwachman score (SS). Compared to controls, children with CCD demonstrated a
      significantly reduced VO2(peak) (P = 0.011), FEV(1) (P < 0.001), FEF(25-75) (P <
      0.001), and a significantly prolonged early (VO2) recovery (P = 0.024). In the CF
      patients the SS was significantly correlated with early VO2 recovery (r = -0.63,
      P = 0.004), FEV(1) (r = 0.72, P = 0.001), and FEF(25-75) (r = 0.57, P = 0.011).
      In the children with CCD, FEV(1), FEF(25-75), and BMI were not significantly
      correlated with VO2(peak) or early VO2 recovery. Lung function does not
      necessarily reflect aerobic fitness and the ability to recover from exercise in
      these patients. A significant relationship was found between VO2(peak) and early
      VO2 recovery (r = -0.39, P = 0.044) in the children with CCD, showing that a
      greater aerobic fitness corresponded with a faster recovery.

PMID- 19382221
TI  - Association of lower airway inflammation with physiologic findings in young
      children with cystic fibrosis.
AB  - BACKGROUND: The relationship between lower airway markers of inflammation and
      infection with physiologic findings is poorly understood in young children with
      cystic fibrosis (CF). The goal of this study was to evaluate the association of
      bronchoalveolar lavage fluid (BALF) markers of infection and inflammation,
      including mediators linked to airway remodeling, to infant lung function values
      in young children with CF undergoing clinically indicated bronchoscopy. METHODS:
      Plethysmography and the raised volume rapid thoracoabdominal compression (RVRTC)
      technique were performed in 16 sedated infants and young children with CF prior
      to bronchoscopy. BALF was collected and analyzed for pathogen density, cell
      count, % neutrophils, transforming growth factor beta 1 (TGF-beta(1)), matrix
      metalloproteinases (MMP), and interleukin-8 (IL-8). RESULTS: There was a
      significant direct correlation between functional residual capacity (FRC), the
      ratio of residual volume to total lung capacity (RV/TLC) and FRC/TLC with %
      neutrophils (P < 0.05). Forced expiratory flows were inversely correlated to %
      neutrophils (P < 0.01). Lung function parameters did not differentiate those with
      and without lower airway infection; however, pathogen density directly correlated
      with FRC and inversely correlated with flows (P < 0.05). In a subset of the
      population, MMP-2 directly correlated with RV/TLC and inversely correlated with
      flows (P < 0.05) and TGF-beta(1) directly correlated with FRC (P < 0.05).
      CONCLUSIONS: Results from this study suggest that lower airway inflammation as
      well as mediators linked to airway remodeling play an active role in pulmonary
      deterioration in CF infants and young children undergoing clinically indicated
      bronchoscopy.

PMID- 19382223
TI  - A histological and immunohistochemical analysis of lymphoid tissues of the
      Tasmanian devil.
AB  - Tasmanian devil lymphoid tissues (thymus, spleen, and lymph node) from seven
      animals, including pouch young, juvenile, and adult devils, were investigated
      using histological and immunohistochemical techniques. Antibodies against the
      conserved intracytoplasmic portion of CD3 and CD79b (T- and B-cell markers,
      respectively) and MHC II were used to label immune cells. The thymus from the
      juvenile devils and the pouch young had CD3+ cells that were primarily located in
      the medulla of the organ. The spleen consisted of red and white pulp areas with
      characteristic lymphoid follicles with CD79b+ and MHC II+ cells and nonfollicular
      T-cell-dominated periarteriolar lymphoid sheaths. Peripheral lymph nodes
      presented three distinct regions, outer cortex and medulla (both with primarily
      CD79b+ and MHC II+ cells) and paracortex (mainly CD3+ cells). Tissue architecture
      and distribution of the immune cells were similar to that seen in eutherian
      mammals and other marsupials, indicating that the Tasmanian devil has all the
      structural elements necessary for effective adaptive immunity.

PMID- 19382224
TI  - Sex steroid receptors in skeletal differentiation and epithelial neoplasia: is
      tissue-specific intervention possible?
AB  - Sex steroids, through their receptors, have potent effects on the signal pathways
      involved in osteogenic or myogenic differentiation. However, a considerable
      segment of those signal pathways has a prominent role in epithelial neoplastic
      transformation. The capability to intervene locally has focused on specific
      ligands for the receptors. Nevertheless, many signals are mapped to interactions
      of steroid receptor motifs with heterologous regulatory proteins. Some of those
      proteins interact with the glucocorticoid receptor and other factors essential to
      cell fate. Interactions of steroid receptor domain motifs with heterologous
      proteins affect specific target pathways; consequently, manipulation of specified
      protein modules complexed with steroid receptors may be a next major step for
      enhancing molecular targeted therapeutics. In the future, intervention at
      specific sections of receptor primary sequence may prove therapeutically more
      efficient in targeting pathways of choice than ligand selectivity can be.

PMID- 19382225
TI  - Spinal microglial proliferation is evident in a rat model of painful disc
      herniation both in the presence of behavioral hypersensitivity and following
      minocycline treatment sufficient to attenuate allodynia.
AB  - Although spinal glia acquire a reactive profile in radiculopathy, glial cell
      proliferation remains largely unstudied. This study investigated spinal glial
      proliferation in a model simulating painful disc herniation; the C7 nerve root
      underwent compression and chromic gut suture exposure or sham procedures. A
      subset of injured rats received minocycline injections prior to injury. Allodynia
      was assessed and bromodeoxyuridine (BrdU) was injected 2 hr before tissue harvest
      on day 1 or 3. Spinal cell proliferation and phenotype identification were
      assayed by fluorescent colabeling with antibodies to BrdU and either glial
      fibrillary acidic protein (astrocytes) or Iba1 (microglia). At day 1, ipsilateral
      allodynia was significantly increased (P < 0.001) for injury over sham.
      Minocycline treatment significantly decreased ipsilateral allodynia to sham
      levels at day 1 (P < 0.001). At day 3, ipsilateral allodynia remained and
      contralateral allodynia was also present for injury (P< 0.003) over sham. The
      number of BrdU-positive cells in the ipsilateral spinal dorsal horn at day 1
      after injury was significantly elevated (P < 0.001) over sham. Approximately 70%
      of BrdU-positive cells labeled positively for Iba1; dividing microglia were
      significantly increased (P < 0.004) in the ipsilateral dorsal horn at day 1
      following injury compared with sham. Spinal cellular proliferation after injury
      was not changed by minocycline injection. By day 3, the number of BrdU-positive
      cells had returned to sham levels bilaterally. Data indicate that spinal
      microglia proliferate after injury but that proliferation is not abolished by
      minocycline treatment that attenuates allodynia, indicating that spinal
      microglial proliferation may be related to injury and may not be linked to
      changes in sensory perception.

PMID- 19382226
TI  - Vascular microarchitecture of murine colitis-associated lymphoid angiogenesis.
AB  - In permissive tissues, such as the gut and synovium, chronic inflammation can
      result in the ectopic development of anatomic structures that resemble lymph
      nodes. These inflammation-induced structures, termed lymphoid neogenesis or
      tertiary lymphoid organs, may reflect differential stromal responsiveness to the
      process of lymphoid neogenesis. To investigate the structural reorganization of
      the microcirculation involved in colonic lymphoid neogenesis, we studied a murine
      model of dextran sodium sulfate (DSS)-induced colitis. Standard 2-dimensional
      histology demonstrated both submucosal and intramucosal lymphoid structures in
      DSS-induced colitis. A spatial frequency analysis of serial histologic sections
      suggested that most intramucosal lymphoid aggregates developed de novo.
      Intravital microscopy of intravascular tracers confirmed that the developing
      intramucosal aggregates were supplied by capillaries arising from the quasi
      polygonal mucosal plexus. Confocal optical sections and whole mount morphometry
      demonstrated capillary networks (185 +/- 46 microm diameter) involving six to ten
      capillaries with a luminal diameter of 6.8 +/- 1.1 microm. Microdissection and
      angiogenesis PCR array analysis demonstrated enhanced expression of multiple
      angiogenic genes including CCL2, CXCL2, CXCL5, Il-1b, MMP9, and TNF within the
      mucosal plexus. Intravital microscopy of tracer particle flow velocities
      demonstrated a marked decrease in flow velocity from 808 +/- 901 microm/sec
      within the feeding mucosal plexus to 491 +/- 155 microm/sec within the capillary
      structures. We conclude that the development of ectopic lymphoid tissue requires
      significant structural remodeling of the stromal microcirculation. A feature of
      permissive tissues may be the capacity for lymphoid angiogenesis.

PMID- 19382227
TI  - Heavy alcohol consumption and neuropathological lesions: a post-mortem human
      study.
AB  - Epidemiological studies have indicated that excessive alcohol consumption leads
      to cognitive impairment, but the specific pathological mechanism involved remains
      unknown. The present study evaluated the association between heavy alcohol intake
      and the neuropathological hallmark lesions of the three most common
      neurodegenerative disorders, i.e., Alzheimer's disease (AD), dementia with Lewy
      bodies (DLB), and vascular cognitive impairment (VCI), in post-mortem human
      brains. The study cohort was sampled from the subjects who underwent a
      medicolegal autopsy during a 6-month period in 1999 and it included 54 heavy
      alcohol consumers and 54 age- and gender-matched control subjects.
      Immunohistochemical methodology was used to visualize the aggregation of beta
      amyloid, hyperphosphorylated tau, and alpha-synuclein and the extent of infarcts.
      In the present study, no statistically significant influence was observed for
      alcohol consumption on the extent of neuropathological lesions encountered in the
      three most common degenerative disorders. Our results indicate that alcohol
      related dementia differs from VCI, AD, and DLB; i.e., it has a different etiology
      and pathogenesis.

PMID- 19382228
TI  - Sustained hydrogen peroxide stress decreases lactate production by cultured
      astrocytes.
AB  - Oxidative stress and disrupted energy metabolism are common to many pathological
      conditions of the brain. Because astrocytes play an important role in the glucose
      metabolism of the brain, we have investigated whether sustained oxidative stress
      affects astroglial glucose metabolism with cultured primary rat astrocytes as a
      model system. Cultured astrocytes were exposed to a sustained concentration of
      approximately 50 muM H(2)O(2) in the presence of [U-(13)C]glucose, and cellular
      and extracellular contents of lactate and glucose were analysed by enzymatic
      assays and NMR spectroscopy. Exposure of the cells to sustained H(2)O(2) stress
      for up to 120 min significantly lowered the rate of lactate accumulation in the
      media to 61% +/- 14% of that in cultures incubated without peroxide. In addition,
      the ratio of lactate release to glucose consumption was lowered in peroxide
      treated astrocytes to 77% +/- 13% of that in control cells, and the specific
      activity of glyceraldehyde-3-phosphate dehydrogenase had declined to about 10% of
      control cells within 90 min. In addition, the (13)C enrichment of intracellular
      and extracellular [(13)C]lactate was about 30% and 95%, respectively, and was not
      affected by the presence of peroxide, demonstrating that two metabolic pools of
      lactate are present in cultured astrocytes. The decreased rate of lactate
      production by astrocytes that have been exposed to peroxide stress is a new
      example of an alteration by oxidative stress of an important metabolic pathway in
      astrocytes. Such alterations could contribute to the pathological conditions that
      have been connected with oxidative stress and disrupted energy metabolism in the
      brain.

PMID- 19382229
TI  - Important roles for epithelial cell peptides in hydra development.
AB  - It has been convincingly shown that peptides play important roles in the
      regulation and maintenance of a variety of tissues and organs in living animals.
      However, little is known concerning the potential role of peptides as signaling
      molecules in developmental processes. In Hydra, there is circumstantial evidence
      that small diffusible molecules act as morphogens in the regulation of patterning
      processes. In order to view the entire spectrum of peptide signaling molecules,
      we initiated a project aiming at the systematic identification of peptide
      signaling molecules in Hydra. In this review, we describe three peptide signaling
      molecules and one family of peptides that function as signaling molecules in the
      processes of axial pattern formation and neuron differentiation in Hydra. These
      peptides are produced by epithelial cells and are therefore termed
      "epitheliopeptides". We discuss the importance of epitheliopeptides in
      developmental processes within a subset of hydrozoans.

PMID- 19382230
TI  - An unstructured protein with destructive potential: TPPP/p25 in
      neurodegeneration.
AB  - TPPP/p25 is a recently discovered, unstructured protein involved in brain
      function. It is found predominantly in oligodendrocytes in normal brain but is
      enriched in neuronal and glial inclusions of Parkinson's disease and other
      synucleinopathies. Its physiological function seems to be the dynamic
      stabilization of microtubular ultrastructures, as well as the projections of
      mature oligodendrocytes and ciliary structures. We reappraise the earlier belief
      that TPPP/p25 is a brain-specific protein. We have identified and cloned two
      shorter (N-terminal-free) homologs of TPPP/p25 that behave differently from each
      other and from TPPP/p25. Two unique cell models have been established and used to
      study the effect of the unstructured protein on the energy metabolism and the
      formation of pathological aggregates. Our data suggest that the intracellular
      level of TPPP/p25 influences the cell differentiation, proliferation and the
      formation of protein aggregates, and consequently, the etiology of central
      nervous system diseases.

PMID- 19382231
TI  - The emerging role of cystatins in Alzheimer's disease.
AB  - Recently opposing effects of cysteine protease inhibitors, the human cystatins,
      on neurodegeneration have been reported. Human cystatin C is a risk factor for
      late-onset Alzheimer's disease (AD), whereas human stefin B (cystatin B) has no
      direct involvement in AD. Conflicting data show that their target protease,
      cathepsin B, might be anti-amyloidogenic, helping in amyloid-beta (Abeta)
      clearance or, instead, might be involved in Abeta production. Some reports claim
      that cystatin C binds soluble Abeta, making transgenic animals healthier, others,
      in contrast, that deleting cystatins genes may contribute to amyloid pathology in
      animal models of AD.

PMID- 19382232
TI  - Comparative anatomy and evolution of the cardiac innervation in New World monkeys
      (Platyrrhini, e. Geoffroy, 1812).
AB  - The morphology of the autonomic cardiac nervous system (ACNS) was examined in 24
      sides of 12 New World monkeys (Platyrrhini) of all four families to document the
      morphology systematically and to study the evolutionary changes of the ACNS in
      this primate lineage. We report the following: (1) Although several trivial intra
      and inter-specific variations are present, a family-dependent morphology of the
      ACNS does not exist in New World monkeys. (2) The sympathetic ganglia in New
      World monkeys consist of the superior cervical, the middle cervical, and the
      cervicothoracic which is composed of the inferior cervical and first and second
      thoracic, and the thoracic ganglia starting with the third thoracic. The general
      cardiac nervous system is the sympathetic middle and inferior cardiac nerves and
      all parasympathetic vagal cardiac branches. (3) The morphology of the ACNS in the
      New World monkeys is almost consistent regardless of the number of vertebrae, the
      cardiac position and deviation (axis), and the great arterial branching pattern
      of the aortic arch, and it is very similar to that in the Old World monkeys, with
      only one difference: the superior cervical ganglion in the New World monkeys
      tends to be relatively smaller, higher, and provides a narrower contribution to
      the spinal nerves than in the Old World monkeys. The ACNS morphology exhibits
      significant evolutionary changes within the primate lineage from New and Old
      World monkeys to humans. The comparative morphology within the lineage is
      concordant with the phylogeny, suggesting that the primate ACNS preserves its
      evolutionary history in close alignment with phylogeny.

PMID- 19382233
TI  - Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective
      in a mouse model of focal cerebral ischemia.
AB  - Asiatic acid, a triterpenoid derivative from Centella asiatica, has shown
      biological effects such as antioxidant, antiinflammatory, and protection against
      glutamate- or beta-amyloid-induced neurotoxicity. We investigated the
      neuroprotective effect of asiatic acid in a mouse model of permanent cerebral
      ischemia. Various doses of asiatic acid (30, 75, or 165 mg/kg) were administered
      orally at 1 hr pre- and 3, 10, and 20 hr postischemia, and infarct volume and
      behavioral deficits were evaluated at day 1 or 7 postischemia. IgG (blood-brain
      barrier integrity) and cytochrome c (apoptosis) immunostaining was carried out at
      24 hr postischemia. The effect of asiatic acid on stress-induced cytochrome c
      release was examined in isolated mitochondrial fractions. Furthermore, its
      effects on cell viability and mitochondrial membrane potential were studied in HT
      22 cells exposed to oxygen-glucose deprivation. Asiatic acid significantly
      reduced the infarct volume by 60% at day 1 and by 26% at day 7 postischemia and
      improved neurological outcome at 24 hr postischemia. Our studies also showed that
      the neuroprotective properties of asiatic acid might be mediated in part through
      decreased blood-brain barrier permeability and reduction in mitochondrial injury.
      The present study suggests that asiatic acid may be useful in the treatment of
      cerebral ischemia.

PMID- 19382234
TI  - Functional and immunocytochemical characterization of D-serine transporters in
      cortical neuron and astrocyte cultures.
AB  - D-serine is an endogenous coagonist of N-methyl-D-aspartate (NMDA) receptors that
      plays an important role in synaptic function, neuronal development, and
      excitotoxicity. Mechanisms of D-serine transport are important in regulation of
      extracellular D-serine concentration and therefore of these critical processes. D
      serine can be transported with low affinity through the Na(+)-dependent amino
      acid transporter termed ASCT2, whereas high-affinity D-serine uptake has been
      reported through the Na(+)-independent transporter termed asc-1. We investigated
      immunoreactivity for ASCT2 and asc-1 and D-serine transport kinetics in cultured
      cortical neurons and astrocytes to gain insight into how D-serine transporters
      regulate CNS D-serine levels. Both neurons and astrocytes exhibited low-affinity
      Na(+)-dependent D-serine uptake (K(T) > 1 mM) with broad substrate selectivity
      that was consistent with uptake through ASCT2. Both neurons and astrocytes also
      stained positively for ASCT2 in immunocytochemistry studies. Neurons but not
      astrocytes stained positively for the high-affinity D-serine transporter asc-1,
      but no evidence of functional asc-1 could be detected in neurons with conditions
      that produced such activity in cortical synaptosomes. These data support ASCT2
      function in both neuron and astrocyte cultures and identify a discrepancy between
      observed asc-1 immunoreactivity and lack of functional asc-1 activity in neuron
      cultures. Together these findings further our knowledge of the processes that
      govern D-serine regulation.

PMID- 19382235
TI  - In vitro analysis of glial cell function in ganglioside-deficient mice.
AB  - Gangliosides are a family of sialic acid-containing glycosphingolipids highly
      enriched in neuronal and glial membranes, where they play pleiotropic roles in
      nervous system function. In this glial cell biological study, we used mice
      deficient in glycosyltransferases involved in ganglioside biosynthesis to gain
      insights into the possible role of ganglioside overexpression or deficiency on
      glial cell proliferation, migration, and differentiation in vitro. Primary
      cultures of olfactory ensheathing cells, oligodendrocyte lineage cells, and
      Schwann cells isolated from beta1,4-N-acetylgalactosaminyl (beta1,4-GalNAc)
      transferase- and alpha-2,8-sialyltransferase-deficient mice demonstrated subtle
      differences in their behavior when compared with wild-type glia. Oligodendrocyte
      axonal interactions were investigated in dissociated embryonic mixed spinal cord
      cultures in which axonal ensheathment with myelin internodes and organized nodes
      of Ranvier form. In these myelinating cultures, deficiency of complex
      gangliosides, as found in beta1,4-GalNAc T(-/-) mice, resulted in the temporal
      disorganization of K(v) and Na(+) channels at the nodes of Ranvier, similar to
      that seen in beta1,4-GalNAc T(-/-) mice in vivo. These data show that
      glycosyltransferase deficiency and the consequent ganglioside imbalance has
      subtle effects on a range of glial cell functions and that in vitro systems can
      be used to explore these in ways that complement whole animal physiology. Our
      results are also consistent with the absence of gross neurodevelopmental
      dysfunction in mice lacking a variety of different gangliosides, suggesting that
      ganglioside redundancy and substitution are mechanisms that compensate for the
      lack of a full complement of complex gangliosides.

PMID- 19382236
TI  - Correlation of the mitochondrial activity of two-cell embryos produced in vitro
      and the two-cell block in Kunming and B6C3F1 mice.
AB  - The correlation between the early embryonic block to development and
      mitochondrial activity was investigated comparing two-cell embryos produced in
      vitro from Kunming (KM) and B6C3F1 mice. One-cell embryos were obtained from two
      species of hybrids (female KM mice mated with KM males and female B6C3F1 mice
      mated with KM males) and cultured for 84 hr in M16 media. The mitochondrial
      membrane potential, ATP content, and reactive oxygen species levels were measured
      in the resulting KM and B6C3F1 two-cell embryos. Mitochondrial membrane potential
      and ATP content were also determined in KM and B6C3F1 metaphase II eggs. The
      results showed that the two-cell block was observed in cultured KM embryos but
      not in B6C3F1 embryos. Mitochondrial membrane potential and ATP content of KM two
      cell embryos were significantly lower than in B6C3F1 two-cell embryos (P < 0.01).
      Interestingly, the reactive oxygen species levels of KM two-cell embryos were
      significantly lower than their B6C3F1 counterparts (P < 0.01). There was no
      difference in mitochondrial membrane potential and ATP content between KM and
      B6C3F1 metaphase II eggs. It is concluded that KM mice have an early two-cell
      embryo block and that a possible "blocking" mechanism is the lower mitochondrial
      membrane potential and ATP content in these embryos. The results suggest a new
      approach for overcoming early embryonic development block, that of manipulating
      mitochondrial activity.

PMID- 19382237
TI  - The enantiomeric composition of linalool and linalool oxide in the flowers of
      kiwifruit (Actinidia) species.
AB  - A survey of linalool enantiomers in kiwifruit (Actinidia) flowers was conducted
      to determine their potential as sources of these valuable floral fragrances, and
      revealed a wide range of enantiomeric ratios. While flowers of A. polygama and A.
      chrysantha contained almost exclusively one enantiomer, most species contained
      significant amounts of both (R) and (S) isomers. In some species enantiomeric
      ratios of floral linalool differed between genotypes, full siblings, and in one
      case clones, and ratios changed from year to year as well as diurnally.
      Enantioselective biosynthesis of the linalool-derived furanoid and pyranoid
      linalool oxides was examined in flowers of an A. chrysantha and an A. polygama
      genotype. The flowers of both species produced almost exclusively (S)-linalool.
      A. chrysantha flowers incubated with rac-d5-linalool preferentially processed the
      (S)-isomer through to the linalool oxides. However, the A. polygama flowers were
      less discriminatory in their use of rac-d5-linalool and processed significant
      quantities of d5-(R)-linalool as well.

PMID- 19382238
TI  - Desacyl-ghrelin and synthetic GH-secretagogues modulate the production of
      inflammatory cytokines in mouse microglia cells stimulated by beta-amyloid
      fibrils.
AB  - Data from Alzheimer's disease (AD) patients and AD animal models demonstrate the
      accumulation of inflammatory microglia at sites of insoluble fibrillar beta
      amyloid protein (fAbeta) deposition. It is known that fAbeta binds to CD36, a
      type B scavenger receptor also involved in internalization of oxidized low
      density lipoprotein (LDL), and initiate a signaling cascade that regulates
      microglial recruitment, activation, and secretion of inflammatory mediators
      leading to neuronal dysfunction and death. The recent demonstration of a binding
      site for the growth hormone secretagogues (GHS) on CD36 prompted us to ascertain
      whether ghrelin and synthetic GHS could modulate the synthesis of inflammatory
      cytokines in fAbeta-activated microglia cells. We demonstrate that N9 microglia
      cells express the CD36 and are a suitable model to study the activation of
      inflammatory cytokines synthesis. In fact, in N9 cells exposed to fAbeta(25-35)
      for 24 hr, the expression of interleukin (IL)-1beta and IL-6 mRNA significantly
      increased. Interestingly, 10(-7) M desacyl-ghrelin, hexarelin, and EP80317 in the
      nanomolar range effectively counteracted fAbeta(25-35) stimulation of IL-6 mRNA
      levels, whereas ghrelin was ineffective. Similarly, the effects of fAbeta(25-35)
      on IL-1beta mRNA levels were attenuated by desacyl-ghrelin, hexarelin, and
      EP80317, but not ghrelin. Because we have observed that the specific GHS receptor
      GHS-R1a is not expressed in N9 cells, the actions of GHS should be mediated by
      different receptors. Reportedly, hexarelin and EP80317 are capable of binding the
      CD36 in mouse macrophages and reducing atherosclerotic plaque deposition in mice.
      We conclude that desacyl-ghrelin, hexarelin, and EP80317 might interfere with
      fAbeta activation of CD36 in microglia cells.

PMID- 19382239
TI  - Development of microglia in the chick embryo spinal cord: implications in the
      regulation of motoneuronal survival and death.
AB  - The role of microglia during normal development of the nervous system is still
      not well understood. In the present study, a chick embryo model was used to
      examine the development of microglia in the spinal cord and characterize their
      changes in response to naturally occurring and pathological death of motoneurons
      (MNs). The microglial response to MN axotomy and the effects of microglial
      activation on MN survival were also studied. We found that: 1)
      macrophages/microglial cells were present in the spinal cord at early
      developmental stages (E3) and that they were recruited after normal and induced
      MN apoptosis; 2) although many microglial cells were seen phagocytosing apoptotic
      bodies, a proportion of dying cells were devoid of engulfing microglia; 3)
      axotomy of mature MNs was accompanied by microglial activation in the absence of
      MN death; 4) excitotoxic (necrotic) MN death provoked a rapid and massive
      microglial recruitment with phagocytic activity; 5) lipopolysaccharide-induced
      microglial activation in vivo resulted in the death of immature, but not mature,
      microglia; and 6) overactivation of microglia modulated the survival of mature
      MNs, either by killing them or by enhancing their vulnerability to die in
      response to a mild injury. Taken together, these observations indicate that
      normal microglia do not play an active role in triggering apoptosis of developing
      MNs. Rather, they act as phagocytes for the removal of dying cells during the
      process of programmed cell death.

PMID- 19382240
TI  - Lentivirus-mediated small interfering RNA targeting VEGF-C inhibited tumor
      lymphangiogenesis and growth in breast carcinoma.
AB  - Lymph node metastasis is a major prognostic factor for patients with breast
      cancer. The activation of vascular endothelial growth factor (VEGF)-C plays a key
      role in lymph node metastasis through promoting lymphangiogenesis. Thus, we
      attempted to elucidate whether small interfering RNAs (siRNA) targeting VEGF-C
      could suppress lymphangiogenesis and lymph node metastasis in vivo. A lentivirus
      based VEGF-C siRNA vector was infected into breast cancer cells and a xenograft
      model. The expression of VEGF-C mRNA and protein were quantified by quantitative
      real-time polymerase chain reaction (QRT-PCR), immunohistochemistry, and western
      blot analysis. The effect of VEGF-C siRNA on breast cancer cells was investigated
      by an invasion assay. Lymphangiogenesis was analyzed with anti-LYVE-1 and anti-D2
      40 by immunohistochemical analysis. Lentivirus-mediated VEGF-C siRNA stably
      reduced VEGF-C mRNA and protein expression. VEGF-C siRNA inhibited the invasive
      ability of breast cancer cells in vitro. Five weeks after intratumoral injection,
      the tumor volume was significantly smaller in the VEGF-C siRNA group than in the
      control scramble siRNA group in the MDA-MB-231 cell xenograft model. The numbers
      of LYVE-1 and D2-40 positive vessels per microscopic field were significantly
      decreased in the VEGF-C siRNA group, which indicates that VEGF-C siRNA inhibited
      lymphangiogenesis. Moreover, lymph node metastasis was significantly suppressed
      by VEGF-C siRNA in vivo. In conclusion, these results indicate that lentivirus
      mediated VEGF-C siRNA offers a new approach for therapeutic intervention to
      prevent tumor growth and lymphatic metastasis of breast cancer.

PMID- 19382241
TI  - Possible promotion of neuronal differentiation in fetal rat brain neural
      progenitor cells after sustained exposure to static magnetism.
AB  - We have previously shown significant potentiation of Ca(2+) influx mediated by N
      methyl-D-aspartate receptors, along with decreased microtubules-associated
      protein-2 (MAP2) expression, in hippocampal neurons cultured under static
      magnetism without cell death. In this study, we investigated the effects of
      static magnetism on the functionality of neural progenitor cells endowed to
      proliferate for self-replication and differentiate into neuronal, astroglial, and
      oligodendroglial lineages. Neural progenitor cells were isolated from embryonic
      rat neocortex and hippocampus, followed by culture under static magnetism at 100
      mT and subsequent determination of the number of cells immunoreactive for a
      marker protein of particular progeny lineages. Static magnetism not only
      significantly decreased proliferation of neural progenitor cells without
      affecting cell viability, but also promoted differentiation into cells
      immunoreactive for MAP2 with a concomitant decrease in that for an astroglial
      marker, irrespective of the presence of differentiation inducers. In neural
      progenitors cultured under static magnetism, a significant increase was seen in
      mRNA expression of several activator-type proneural genes, such as Mash1, Math1,
      and Math3, together with decreased mRNA expression of the repressor type Hes5.
      These results suggest that sustained static magnetism could suppress
      proliferation for self-renewal and facilitate differentiation into neurons
      through promoted expression of activator-type proneural genes by progenitor cells
      in fetal rat brain.

PMID- 19382242
TI  - Geometric morphometric investigation of molar shape diversity in modern lemurs
      and lorises.
AB  - In the study of mammalian adaptation to the environment, teeth are of primary
      importance due to their role as one of the direct interaction points between an
      individual and its ecological surroundings. Here, molar shape and function are
      investigated through traditional multivariate statistics and Thin-Plate Splines
      deformations to compare the relative location of lower first molar occlusal
      structures (protoconid, metaconid, hypoconid, entoconid, cristid obliqua, and
      protolophid) in modern lemurs, lorises, tarsiers, and a non-primate outgroup
      taxon (Tupaia). Results suggest that shape is based both on tooth size and
      dietary patterns. Small teeth tend to be short (anteroposteriorally) with wide
      talonids, whereas larger teeth are generally characterized as being long and
      narrow. In considering non-size related shape trends, frugivorous and
      graminivorous taxa generally exhibit a relatively buccal intersection of the
      cristid obliqua with the base of the protolophid, and a relatively
      "perpendicular" position of the protolophid in relation to the anteroposterior
      axis of the tooth (defined as the axis connecting the protolophid and hypoconid).
      Morphological trends of folivores include a central (midline) position of the
      cristid obliqua-protolophid base intersection and an oblique angle of the
      protolophid. Insectivorous taxa (primate and non-primate) generally exhibit a
      central placement of the cristid obliqua-protolophid base intersection (as in
      folivores), along with a relatively perpendicular angle of the protolophid (as in
      frugivores). Omnivorous taxa exhibit shape patterns that are intermediate between
      these three former groups. This study provides a comparative baseline for the
      interpretation of morphological trends in fossil primate groups, particularly the
      Adapiformes.

PMID- 19382243
TI  - Quantitative determination of a novel enantiomeric tropane analog, (-)-satropane,
      in biological fluids using liquid chromatography/tandem mass spectrometry.
AB  - A sensitive, accurate and precise liquid chromatography-tandem mass spectrometry
      method was developed for the determination of (-)-satropane (3alpha-paramethyl
      benzenesulfonyloxy-6beta-acetoxy-tropane) in rabbit aqueous humor. Since (-)
      satropane may be absorbed from the aqueous humour with resultant systemic side
      effects, the LC-MS/MS method was also evaluated for its applicability in
      analyzing plasma samples containing this compound. (-)-Satropane and phentolamine
      (the internal standard, represented as IS) were detected by multiple reaction
      monitoring using the transitions m/z 354-182 and 282-212, respectively. The
      calibration curve was linear over the ranges 2-500 and 5-1000 ng/mL, and the
      values of the lower limit of quantification were 2 and 5 ng/mL for the
      microdialysis dialysate and rat plasma samples, respectively. The intra-day and
      inter-day precision and accuracy were better than 8.6 and 6.00%, respectively, in
      both matrices investigated. The absolute recovery of the plasma samples was more
      than 76.30%. The average matrix effects of (-)-satropane were 91.72 and 83.05% in
      the microdialysis dialysate and plasma samples, respectively. The validated
      method was successfully applied to analyze (-)-satropane in microdialysis
      dialysate and rat plasma samples, and this assay has been used to quantify (-)
      satropane in the pharmacokinetic and toxicokinetic studies in our laboratory.

PMID- 19382244
TI  - Determination of teniposide in rat plasma by ultra performance liquid
      chromatography electrospray ionization tandem mass spectrometry after intravenous
      administration.
AB  - A novel, specific and rapid ultra performance liquid chromatography electrospray
      ionization tandem mass spectrometry method has been developed and validated for
      determination of teniposide in rat plasma. A one-step liquid-liquid extraction
      method was used and the separation was carried out on an Acquity UPLC(TM) BEH
      C(18) column with gradient elution using a mobile phase composed of acetonitrile
      and water (containing 0.1% formic acid) at a flow rate of 0.20 mL/min. A triple
      quadrupole tandem mass spectrometer in multiple-reaction monitoring mode via an
      electrospray ionization interface was used for the detection of teniposide. The
      detection was complete within 3.0 min. A linear calibration curve was obtained
      over the concentration range 10-10,000 ng/mL for teniposide, with a lower limit
      of quantification of 10 ng/mL. The intra-day precision and inter-day precision
      (relative standard deviation) were less than 10.23 and 13.09%, respectively. The
      developed method was applied for the first time to the pharmacokinetic study of
      teniposide in rats following a single intravenous administration of 4.5 mg/kg
      teniposide.

PMID- 19382245
TI  - Plasma phospholipid metabolic profiling and biomarkers of rats following
      radiation exposure based on liquid chromatography-mass spectrometry technique.
AB  - Lipidomics, a prominent area of metabolomics, utilizes novel analytical
      methodologies to study the extensive classes of lipid molecules, changes in lipid
      metabolism and lipid-mediated signaling processes. In this paper, the
      phospholipid metabolic profiles changes and potential biomarker identification in
      the rats plasma after gamma-irradiation exposure were investigated by coupling
      high performance liquid chromatography-mass spectrometry technology to
      multivariate statistical analysis. Orthogonal partial least-squares to latent
      structures discriminate analysis (OPLS-DA) was used to find the potential plasma
      phospholipids biomarkers of rats for radiation exposure. According to the
      corresponding tandem mass spectrometric results, potential biomarkers were
      identified. After exposure to gamma-rays, phosphatidylethanolamine and
      phosphatidylserine showed a marked increase, and phosphatidylcholine,
      sphingomyelin and lysophosphatidylcholine followed the same trend, although their
      rise was not significant. The results suggested that radiated rats had a
      phospholipid metabolic abnormality, which could be an alternative way to assess
      the radiaton exposure. The biomarkers may involve a radiation-induced apoptosis
      pathway and represent a promising target for discovery new radioprotective drugs
      and radiosensitizers.

PMID- 19382246
TI  - Isolation and purification of isoflavonoids from Rhizoma Belamcandae by two
      dimensional preparative high-performance liquid chromatography with column switch
      technology.
AB  - A two-dimensional column-switching system without sample loop trapping, where two
      columns were operated via a six-port switching valve, was employed in the
      isolation and purification of five isoflavonoids from Rhizoma Belamcandae:
      tectoridin, iridin, tectorigenin, irigenin and irisflorentin. The introduction of
      the six-port switching value, instead of a sample loop, assured 100% recovery
      from the first dimension to the second, and the injection volumes of the second
      dimension were not restricted. Two configurations were tested in this study. In
      the first mode, only one column was used in the second dimension and two 'heart
      cutting' fractions were transported to the same second-dimensional column. In the
      second mode, two parallel columns were used in the second dimension and two
      fractions were transported to the two columns. Between the two configurations,
      the one with two second dimensional columns had double sample size, better
      resolution and one more purified compound. Both two-dimensional configurations
      consumed less solvent with even greater efficiency and shorter cycle time
      compared with conventional gradient methods. All of the isoflavonoids were
      isolated at high purities of greater than 95% with yields of above 82%.

PMID- 19382247
TI  - Insulin-producing cells derived from rat bone marrow and their autologous
      transplantation in the duodenal wall for treating diabetes.
AB  - Islet cell transplantation is one of the most promising therapies for diabetes
      mellitus (DM). However, the limited availability of purified islets for
      transplantation and the risk of immunological rejection severely limit its use.
      In vitro transdifferentiation of autologous bone marrow-derived mesenchymal stem
      cells (BMSCs) into insulin-producing cells (IPCs) could provide an abundant
      source of cells for this procedure and avoid immunological rejection. Here, we
      isolated and characterized BMSCs and induced their in vitro differentiation into
      IPCs. Reverse-transcription polymerase chain reaction analysis revealed that
      these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and
      pancreatic duodenal homeobox-1. Insulin production by the IPCs was confirmed by
      immunocytochemistry and Western blot analysis. On this basis, donor rats
      supplying BMSCs were made diabetic by a single intraperitoneal injection of
      streptozotocin. The IPCs were then autologously transplanted into the duodenal
      submucosa of diabetic rats. Grafted cells could be visualized in sections after
      2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in
      the IPC-implanted group, hyperglycemia was normalized, compared with a persistent
      increase in glucose levels in the diabetic group and intraperitoneal glucose
      tolerance test-induced responses were observed in the IPC-implanted group. These
      results on autologous transplantation of IPCs derived from BMSCs into the
      duodenal wall could offer a novel potential therapeutical protocol for DM.

PMID- 19382248
TI  - Hydrophobic interaction chromatography in dual salt system increases protein
      binding capacity.
AB  - Hydrophobic interaction chromatography (HIC) uses weakly hydrophobic resins and
      requires a salting-out salt to promote protein-resin interaction. The salting-out
      effects increase with protein and salt concentration. Dynamic binding capacity
      (DBC) is dependent on the binding constant, as well as on the flow
      characteristics during sample loading. DBC increases with the salt concentration
      but decreases with increasing flow rate. Dynamic and operational binding capacity
      have a major raw material cost/processing time impact on commercial scale
      production of monoclonal antibodies. In order to maximize DBC the highest salt
      concentration without causing precipitation is used. We report here a novel
      method to maintain protein solubility while increasing the DBC by using a
      combination of two salting-out salts (referred to as dual salt). In a series of
      experiments, we explored the dynamic capacity of a HIC resin (TosoBioscience
      Butyl 650M) with combinations of salts. Using a model antibody, we developed a
      system allowing us to increase the dynamic capacity up to twofold using the dual
      salt system over traditional, single salt system. We also investigated the
      application of this novel approach to several other proteins and salt
      combinations, and noted a similar protein solubility and DBC increase. The
      observed increase in DBC in the dual salt system was maintained at different
      linear flow rates and did not impact selectivity.

PMID- 19382249
TI  - Physiology of Aspergillus niger in oxygen-limited continuous cultures: Influence
      of aeration, carbon source concentration and dilution rate.
AB  - In industrial production of enzymes using the filamentous fungus Aspergillus
      niger supply of sufficient oxygen is often a limitation, resulting in the
      formation of by-products such as polyols. In order to identify the mechanisms
      behind formation of the different by-products we studied the effect of low oxygen
      availability, at different carbon source concentrations and at different specific
      growth rates, on the metabolism of A. niger, using continuous cultures. The
      results show that there is an increase in the production of tricarboxylic acid
      (TCA) cycle intermediates at low oxygen concentrations. Indeed, at these
      conditions, a decrease in the mitochondrial respiratory chain activity leads to
      an accumulation of NADH and to a decreased ATP production which uncouples
      catabolism and anabolism, influences the intracellular pH and leads to production
      and excretion of organic acids. Moreover, mannitol is being produced in order to
      ensure reoxidation of NADH, and this is the main cellular response to balance the
      ratio NADH/NAD at low oxygen availability. Mannitol production is also coupled to
      low specific growth rate, which suggests a control of carbon catabolite
      repression on the mannitol pathway. The roles of two other polyols, erythritol
      and glycerol, were also investigated. Both compounds are known to accumulate
      intracellularly, at high osmotic pressure, in order to restore the osmotic
      balance, but we show that the efficiency of this system is affected by a leakage
      of polyols through the membrane.

PMID- 19382250
TI  - Frequent detection of hepatitis B virus variants associated with lamivudine
      resistance in treated South African patients infected chronically with different
      HBV genotypes.
AB  - This retrospective study investigated and characterized the YMDD motif of the
      hepatitis B virus (HBV) reverse transcriptase (RT) gene, in sequential samples of
      17 South African patients with chronic hepatitis B infection on lamivudine
      treatment. The profile of HBV genotypes as well as the genetic variability of pre
      core (pre-C) and basal core promoter regions (BCP) were also determined in these
      patients. Mutations within the RT gene were determined by direct sequencing using
      SpectruMedix SCE 2410 genetic analyzer and INNO-LiPA HBV DR (Innogenetics), while
      the genetic variability of the pre-C/BCP and surface gene were determined by
      direct sequencing only. HBV genotypes were determined by analysis of the surface,
      core and RT genes using a web-based genotyping tool (NCBI). HBV DNA was
      quantified using Cobas Amplicor HBV Monitor assay (Roche Diagnostics). Of the 17
      patients, 13 (76.5%) carried YMDD mutations: 7 with rtM204I (2 HBeAg-positive and
      5 HBeAg-negative) and 6 with rtM204V (4 HBeAg-positive and 2 HBeAg-negative). Of
      the 13 patients with resistant HBV strains, 8 (61.5%) carried genotype A, 3 (23%)
      genotype B, and 2 (15.3%) genotype C. Overall, only 5 of 13 (38%) patients with
      YMDD mutations experienced genotypic viral drug resistance and treatment failure.
      Of the 17 patients, 3 carried both pre-C (G1896A) and BCP (A1762T/G1764A)
      mutants, 1 pre-C only and 1 BCP only. This study demonstrated frequent detection
      of mutations associated with lamivudine-resistance in therapy-experienced South
      African patients infected chronically with different HBV genotypes, and confirmed
      that these mutations are not always accompanied by clinical relapse.

PMID- 19382252
TI  - Prevalence of human immunodeficiency virus and its association with hepatitis B,
      C, and D virus infections among incarcerated male substance abusers in Taiwan.
AB  - Taiwan has been facing a rising epidemic of human immunodeficiency virus (HIV)
      infection since 2004. Injection drug users comprised 38.5% of accumulated HIV
      cases by 2007. This cross-sectional study investigated the seroprevalence of
      hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and
      HIV infection in 753 male substance users who were detained in a detoxification
      center in Taoyuan, Taiwan. The subjects were enrolled into the study
      consecutively between February and October, 2005. The seroprevalence rates of HIV
      antibodies, HCV antibodies, and HBV surface antigens among all subjects, and HDV
      antibodies among HBV carriers were 6.9% (95% confidence interval [CI]: 5.19
      8.95), 30.5% (95% CI: 27.23-33.93), 16.9% (95% CI: 14.24-19.71) and 13.7% (95%
      CI: 8.19-21.04), respectively. Subjects in the heroin injection group had
      significantly higher rates of HIV infection, HCV infection and HDV superinfection
      (25.5%, 89.6%, and 38.7%) than those in the heroin non-injection group (0.9%,
      24.5%, and 6.25%), the methamphetamine group (0.3%, 8.1%, and 6.7%), and the club
      drug group (1%, 3%, and 0%; P < 0.001). The odds of HCV, HIV, or HDV infection
      were 74.7, 63.8, and 11.1 higher, respectively, for heroin injection drug users
      than for non-injection drug users (P < 0.0001). Compared to HIV-negative
      individuals, the odds of being a heroin injector and the odds of HCV co
      infections were 64-fold and 149-fold higher, respectively, in HIV-positive
      individuals. The impact of HBV, HCV, and HDV infection on the HIV epidemic in
      Taiwan should be monitored closely.

PMID- 19382251
TI  - Prospective cohort study of mother-to-infant infection and clearance of hepatitis
      C in rural Egyptian villages.
AB  - Although persistent transmission of hepatitis C virus (HCV) from infected mothers
      to their infants is reported in 4-8%, transient HCV perinatal infection also
      occurs. This prospective cohort study determined perinatal HCV infection- and
      early and late clearance-rates in 1,863 mother-infant pairs in rural Egyptian
      villages. This study found 15.7% and 10.9% of pregnant women had HCV antibodies
      (anti-HCV) and HCV-RNA, respectively. Among 329 infants born of these mothers, 33
      (10.0%) tested positive for both anti-HCV and HCV-RNA 2 months following birth-29
      (12.5%) having HCV-RNA positive mothers and 4 (with transient infections) having
      mothers with only anti-HCV. Fifteen remained HCV-RNA positive at one and/or 2
      years (persistent infections), while 18 cleared both virus and antibody by 1 year
      (transient infections). Among the 15 persistent cases, 7 cleared their infections
      by 2 or 3 years. At 2- to 6- and at 10- to 12-month maternally acquired anti-HCV
      was observed in 80% and 5% of infants, respectively. Four perinatally infected
      and one transiently infected infant were confirmed to be infected by their
      mothers by the sequence similarity of their viruses. Viremia was 155-fold greater
      in mothers of infants with persistent than mothers of infants with transient
      infections. Maternal-infant transmission of HCV is more frequent than generally
      reported. However, both early and late clearance of infection frequently occurs
      and only 15 (4.6%) and 8 (2.4%) infants born of HCV-RNA positive mothers had
      detectable HCV-RNA at one and 2-3 years of age. Investigating how infants clear
      infection may provide important information about protective immunity to HCV.

PMID- 19382253
TI  - Modified adult measles in outbreaks in Japan, 2007-2008.
AB  - Different genotypes of C1, D3, D5, and H1 were isolated in outbreaks of 1984,
      1987-1988, 1991-1993, and 2001, respectively, when the previous circulating
      genotype was replaced successively by a new genotype, through molecular studies
      of measles since 1984 in Japan. In March 2007, several patients with measles were
      observed in outpatient clinics, who were all young adolescents in high school and
      university students. The outbreak expanded subsequently throughout Japanese
      districts in May and is still ongoing in 2008. Reverse transcription loop
      mediated isothermal amplification (RT-LAMP) was used to detect the measles genome
      from 18 clinical samples obtained from patients suspected of modified measles
      infection with a very mild febrile illness. The measles genome was detected in
      nine patients by reverse transcription polymerase chain reaction (RT-PCR) and in
      12 patients by RT-LAMP. Six measles strains were isolated in the 2007-2008
      outbreak and identified as the D5 genotype (MVi/Bangkok.THA/93 type) different
      from the D5 sub-cluster (MVi/Palau.BLA/93 type) isolated in 1990-2005. Similar
      Bangkok type D5 strains were isolated in Phnom Penh in 2002 and in Taiwan in
      2003, suggesting that the D5 strains might have been introduced via South East
      Asia, rather than resulting from the accumulation of mutations in the D5 strains
      of 1990-2005. One D9 strain was isolated from a sporadic case in Aichi in 2006.
      There was no difference in the antigenicity of the D9 and D5 strains in
      comparison with the vaccine strain. Infrastructure of systematic laboratory-based
      surveillance system should be established in order to confirm measles virus
      infection in Japan.

PMID- 19382254
TI  - Absence of genotypic drug resistance and presence of several naturally occurring
      polymorphisms of human immunodeficiency virus-1 CRF06_cpx in treatment-naive
      patients in Estonia.
AB  - All non-B HIV-1 subtypes and circulating recombinant forms (CRFs) are
      characterized by several polymorphisms in protease (PR) region. In addition, in
      recent years the increasing use of antiretroviral treatment (ART) has rapidly
      raised the spread of transmitted drug resistance. We aimed to determine the
      presence of naturally occurring polymorphisms and transmitted drug resistance
      mutations (DRMs) in ART naive HIV-1-positive subjects in Estonia. A total of 115
      drug-naive HIV-1-infected subjects (mean age 27 years; 70% male; 65% infected via
      intravenous drug use and 34% by heterosexual contact) were enrolled. Viral
      genomic RNA from plasma was directly sequenced in PR, revertase (RT), and
      envelope (env) regions. Phylogenetic analysis of RT and env regions revealed that
      89% and 3% of sequenced viruses belonged to CRF06_cpx and subtype A1,
      respectively, and 6% were described as unique recombinants (signed A1-06) between
      CRF06_cpx and subtype A1 viruses. No primary DRMs were found in PR or RT regions
      indicating the absence of transmitted drug resistance. The most common
      polymorphisms in the PR region were K14R, M36I, H69K, and L89M seen in 96%, 100%,
      99%, and 100%, respectively. The clinical relevance of these polymorphisms in
      terms of success of ART has to be monitored in future clinical studies.

PMID- 19382255
TI  - Varying abilities of recombinant polypeptides from different regions of hepatitis
      E virus ORF2 and ORF3 to detect anti-HEV immunoglobulin M.
AB  - Following infection with hepatitis E virus (HEV), anti-HEV immunoglobulin (Ig) M
      is thought to develop before anti-HEV IgG and to be a better marker for
      differentiating between the acute and convalescent phases of infection. In order
      to select polypeptides for improved detection of anti-HEV IgM, six and three
      overlapping polypeptides from open reading frames (ORFs) 2 and 3, respectively,
      of HEV genotypes 1 and 4 were expressed as fusion proteins in Escherichia coli.
      The reactivities of the polypeptides with anti-HEV IgM were evaluated using
      immunoblotting and enzyme immunoassays (EIAs). The data indicated that
      polypeptides from the N-terminus of ORF3 and middle region of ORF2 were weakly or
      not reactive with anti-HEV IgM, while those from the remaining regions of ORF2
      and ORF3 contained reactive epitopes. Anti-HEV IgM against the N- or C-terminus
      of ORF2 appeared earlier and disappeared faster than that against polypeptides
      from the C-terminus of ORF3, based on serum samples from rhesus monkeys infected
      experimentally, and from patients infected naturally, with HEV. The N- and C
      terminal polypeptides from ORF2 complemented one another in detecting anti-HEV
      IgM and EIA sensitivity was improved significantly with a combination of these
      polypeptides. The reactivities of ORF2 polypeptides from genotypes 1 and 4 were
      similar but that of ORF3 differed with sera from monkeys infected by the two
      genotypes. Thus, a combination of N- and C-terminal polypeptides of ORF2 from one
      genotype may be effective in EIAs to detect anti-HEV IgM.

PMID- 19382257
TI  - Gene expression profiling by microarray analysis reveals an important role for
      caspase-1 in dengue virus-induced p53-mediated apoptosis.
AB  - Recently, a dengue virus-induced apoptosis p53- and mitochondria-mediated were
      reported in human and animal cells. To understand further the underlying
      mechanisms, a p53-deficient cell line, H1299, and a p53-knockin cell line, H273,
      were infected with dengue type 1 virus and the cellular gene expression profiles
      at the mRNA level were analyzed by affymetrix array analysis. The results showed
      183 genes with at least twofold increase at mRNA expression level in dengue virus
      infected cells. Among the 183 genes, 68 genes were up-regulated in both H1299 and
      H273 cells and 78 genes were found to be up-regulated in only H273 cells. Eleven
      selected genes, mainly involved in IFN-pathway, cell cycle, signal transduction,
      and ubiquitin-proteasome pathways were confirmed using qualitative and
      quantitative PCR. Interestingly, an approximately 32-fold increase in caspase-1
      expression was observed in the p53-knockin cell line, H273. Gene silencing of
      caspase-1 or inhibition of caspase-1 activity led to reduction in dengue virus
      induced apoptosis with minimal effect on virus replication.

PMID- 19382256
TI  - Serological evidence for long-term Epstein-Barr virus reactivation in children
      living in a holoendemic malaria region of Kenya.
AB  - To study the long term the effects of chronic exposure to P. falciparum malaria
      on Epstein-Barr virus (EBV) reactivation in children, EBV-specific antibody
      levels were measured in a cross-sectional survey of two groups of Kenyan children
      with divergent malaria exposure, varying in age from 1 to 14 years. A total of
      169 children were analyzed within three age groups (1-4 years, 5-9 years and 10
      14 years). Using a Luminex assay, elevated levels of IgG to EBV lytic and latent
      antigens were observed in children from the holoendemic malaria area; these
      remained elevated for each age group studied. In comparison, children from the
      sporadic malaria area had lower levels of EBV-specific IgG antibodies and these
      levels declined across age groups. These data suggest that chronic exposure to
      malaria may lead to long-term EBV reactivation.

PMID- 19382258
TI  - Frequent detection of hepatitis B virus DNA in hepatocellular carcinoma of
      patients with sustained virologic response for hepatitis C virus.
AB  - Hepatocellular carcinoma (HCC) develops several years after the eradication of
      hepatitis C virus (HCV) by interferon therapy. Risk factors for the development
      of HCC are only partly understood. To elucidate the role of occult hepatitis B
      virus (HBV) infection in hepatocarcinogenesis in patients with sustained
      virologic response, the prevalences of HBV-related makers were examined. Study
      group comprised 16 patients with sustained virologic response (group A) and 50
      with HCV (group B). Anti-HBc and anti-HBs in serum were examined by enzyme-linked
      immunoassay. HBV DNA in liver was examined by nested polymerase chain reaction,
      using primers specific for genes encoding for HBx, HBsAg, HBcAg, and HBV cccDNA.
      Sequence of the amplified HBV DNA for 'a' determinant of HBsAg was determined in
      HCC. Anti-HBc was positive in 10 of 16 in group A and 25 of 50 in group B. HBV
      DNA in liver was detected in 12 of 16 in group A and 21 of 50 in group B (P =
      0.044). In group A, HBV DNA in liver was detected frequently in patients without
      cirrhosis and in those with a longer period from the time of HCV eradication to
      the development of HCC. Mutation in 'a' determinant of HBsAg was found in three
      HCC of group A. Occult HBV infection may be one of the most important risk
      factors in hepatocarcinogenesis of Japanese patients with sustained virologic
      response.

PMID- 19382259
TI  - Case report: clearance of hepatitis C virus after changing the HAART regimen in a
      patient infected with hepatitis C virus and the human immunodeficiency virus.
AB  - The effect of highly active antiretroviral therapy (HAART) on hepatitis C virus
      (HCV) infection remains uncertain. This report describes the case of a man with
      hemophilia with HIV-HCV coinfection with persistent disappearance of HCV RNA
      after changing the HAART regimen. He had been treated with zidovudine,
      lamivudine, and indinavir for initial HAART and the HIV RNA level had been
      undetectable for more than 8 years. He had suffered from chronic active
      hepatitis. The HAART regimen was changed to emtricitabine/tenofovir, atazanavir,
      and ritonavir because the patient preferred a once daily regimen. The HCV RNA
      level fell immediately and thereafter became undetectable by quantitative and
      qualitative assay at 5 and 7 months after the change of the HAART regimen,
      respectively. In contrast to other reported cases, he experienced neither
      increase of CD4+ T cells count nor ALT flare-ups before HCV RNA clearance. The
      HCV RNA disappearance in this case may be due to the direct effect of HAART
      against HCV rather than restoration of cellular immunity to HCV.

PMID- 19382260
TI  - Sequence-specific detection method for reverse transcription, loop-mediated
      isothermal amplification of HIV-1.
AB  - HIV diagnosis at the point-of-care or in resource-limited settings poses
      considerable challenges due to time and cost limitations. Currently, nucleic acid
      based tests are the only reliable method for diagnosing recent infections during
      the window period post-infection and pre-seroconversion, but these tests are only
      suitable for well-equipped laboratory settings. The reverse transcription loop
      mediated isothermal amplification (RT-LAMP) technology exhibits characteristics
      that are ideal for the development of a rapid, cost-effective nucleic acid-based
      test for detection of HIV DNA and RNA. In this study, a sequence-specific
      detection method was developed for immediate, naked-eye visualization of RT-LAMP
      products with high sensitivity and specificity. The rapid detection method was
      incorporated into the HIV-1-specific RT-LAMP assay and validated using minute
      volumes of whole blood from HIV-1-infected individuals. Together with the minimal
      sample preparation time and one-step, isothermal amplification reaction, the
      sequence-specific detection method adds to the overall versatility of the RT-LAMP
      assay and enhances the applicability for use at point-of-care or resource-limited
      sites.

PMID- 19382261
TI  - Validation of a sensitive and specific real-time PCR for detection and
      quantitation of hepatitis B virus covalently closed circular DNA in plasma of
      chronic hepatitis B patients.
AB  - Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) serves as a
      template for viral replication and plays a role in persistence of HBV infection.
      The origin and significance of cccDNA in plasma however, is not well understood.
      A sensitive, specific, and reproducible real-time PCR for detection and
      quantitation of cccDNA in plasma of chronic hepatitis B patients was developed
      and validated. Four HBV DNA reference panels, and 96 plasma samples of chronic
      hepatitis B patients were analyzed. Results were compared with total HBV DNA
      levels, individual ALT levels and the Histology Activity Index (HAI). This cccDNA
      assay had a lower limit of detection at 15 copies/PCR, a lower limit of
      quantitation at 91 copies/PCR and a correlation coefficient (R) of 0.98 (P <
      0.0001). cccDNA was detected in two of four international panels. Significant
      correlation was found between cccDNA and total HBV DNA levels in both panels (R =
      0.96, and R = 0.43) and in samples of the chronic hepatitis B patients (R = 0.88,
      P < 0.0001). In 57% of these samples cccDNA was detectable. Mean level of cccDNA
      was 0.16% of total HBV load. Plasma cccDNA levels were higher in HBeAg positive
      samples than in HBeAg negative samples (4.91 log copies/ml vs. 3.88 log
      copies/ml, P < 0.0001). Levels of total HBV DNA and HBV genotype did not
      influence cccDNA detection. ALT levels and HAI-score were not correlated with
      plasma cccDNA levels. These findings suggest that cccDNA levels in plasma are not
      the result of increased hepatocyte degeneration, but indicate that other
      mechanisms might be responsible.

PMID- 19382262
TI  - Association of IL-4 589 C/T promoter and IL-4RalphaI50V receptor polymorphism
      with susceptibility to HIV-1 infection in North Indians.
AB  - The clinical course and outcome of HIV-1 infection are highly variable among
      individuals. Interleukin 4 (IL-4) is a key T helper 2 cytokine with various
      immune-modulating functions including induction of immunoglobulin E (IgE)
      production in B cells, downregulation of CCR5 and upregulation of CXCR4, the main
      co-receptors for HIV. Our objective is to investigate whether single-nucleotide
      polymorphisms (SNPs) in the IL-4 promoter 589 C/T and IL-4 Ralpha I50V affect the
      susceptibility to HIV infection and its progression to AIDS in North Indian
      individuals. The study population consisted of 180 HIV-1 seropositive (HSP)
      stratified on the basis of disease severity (stage I, II, III), 50 HIV-1 exposed
      seronegative (HES), and 305 HIV-1 seronegative (HSN) individuals. The subjects
      were genotyped for IL-4 589 C/T promoter polymorphism and IL-4 Ralpha I50V by
      polymerase chain reaction restriction fragment length polymorphism. The results
      showed that IL-4 589 C/T was not associated with the risk of HIV infection and
      disease progression. However, the IL-4Ralpha I50 allele and genotype was
      significantly increased in HSP compared to HSN and HSP and was associated with
      risk of HIV infection. The frequency of IL-4Ralpha I50 allele in the HSP group
      was higher than in HSN (76.11 vs. 64.75%; P = 0.000; OR = 1.734) and HES (76.11%
      vs. 62.00%; P = 0.007; OR = 1.953). Homozygous IL-4Ralpha I50I genotype was
      significantly increased in HSP group compared with HSN (58.88% vs. 44.26%; P =
      0.002; OR = 1.804) and HES (58.88% vs. 42.00%; P = 0.038; OR = 1.978). The
      present study for the first time suggests an association of IL-4Ralpha I50 allele
      with increased likelihood of HIV-1 infection in North Indian population. Further
      studies are required to confirm these findings and understand the effect of IL
      4Ralpha polymorphism on the outcome of HIV-1 infection.

PMID- 19382264
TI  - Loop-mediated isothermal amplification-based diagnostic assay for monkeypox virus
      infections.
AB  - Monkeypox virus (MPXV) causes a smallpox-like disease in non-human primates and
      humans. This infection is endemic to central and western Africa. MPXV is divided
      into two genetically different groups, Congo Basin and West African MPXV, with
      the former being the more virulent. A real-time quantitative MPXV genome
      amplification system was developed for the diagnosis of MPXV infections using
      loop-mediated isothermal amplification (LAMP) technology. Primers used for genome
      amplification of Congo Basin (C-LAMP), West African (W-LAMP), and both Congo
      Basin and West African (COM-LAMP) MPXV by LAMP were designed according to the
      nucleotide sequences of the Congo Basin-specific D14L gene, the West African
      specific partial ATI gene, and the partial ATI gene that is shared by both
      groups, respectively. The sensitivity and specificity of the LAMP were evaluated
      with nested PCR using peripheral blood and throat swab specimens collected from
      Congo Basin MPXV or West African MPXV-infected monkeys. The sensitivity and
      specificity of COM-LAMP, C-LAMP, and W-LAMP were 80% (45/56) and 100% (64/64);
      79% (19/24) and 100% (24/24); and 72% (23/32) and 100% (40/40), respectively. The
      viremia level determined by LAMP assays increased with increases in the severity
      of the monkeypox-associated symptoms. The newly developed LAMP assay was
      confirmed to be a rapid, quantifiable, and highly sensitive and specific system
      effective in the diagnosis of MPXV infections. The LAMP assays made it possible
      to discriminate between Congo Basin and West African MPXV. The LAMP developed in
      this study is useful not only for diagnosis of but also for the assessment of
      MPXV infections.

PMID- 19382265
TI  - Molecular epidemiology of hepatitis E virus in Hong Kong.
AB  - Hepatitis E virus (HEV) is one of the major causes of acute and self-limiting
      hepatitis in human. In Hong Kong, the number of notifications increased from 26
      to 62 from year 2001 to 2007. This study describes the molecular epidemiology of
      HEV in Hong Kong in order to determine the movement and distribution of HEV. HEV
      in 171 serum samples from HEV IgM positive cases from year 2001 to 2007 were
      amplified using RT-PCR and subjected to nucleotide sequencing. Phylogenetic
      analysis showed 162 of 171 HEV detected cases (94.7%) belonged to genotype IV and
      8 (4.7%) to genotype I. Interestingly, a cluster of 10 cases in year 2007 that
      had the same sequence of HEV was identified. Epidemiological data however did not
      detect any relationship between these cases. Since zoonotic transmission is a
      well known route of HEV infection, close monitoring of the circulating HEV
      strains in human and food source animals may help to provide additional
      information on the transmission of HEV and possible source of infection in Hong
      Kong.

PMID- 19382263
TI  - Genetic variability of hepatitis C virus in South Egypt and its possible clinical
      implication.
AB  - Egypt is one of the countries with very high rates of hepatitis C virus (HCV)
      related morbidity and mortality. However, little is known about geographical and
      clinical differences in genetic variability of HCV in Egypt. Using direct
      sequencing and phylogenetic analysis of partial core/E1 and NS5B regions of the
      HCV genome, HCV genotype/subtype was determined in 129 HCV-infected patients
      residing in three governates in south Egypt: Assuit, Sohag, and Qena. According
      to clinical stage of infection, patients were categorized into four groups:
      asymptomatic carriers, n = 16; chronic hepatitis C patients, n = 36; liver
      cirrhosis, n = 54; and hepatocellular carcinoma (HCC), n = 23. Genotype 4a was
      detected in 80.6%, whereas 1g, 4l, 4n, 4o, 4f, and 4m were identified in 7.7%,
      4.7%, 3.9%, 1.6%, 0.8%, and 0.8% of cases, respectively. The prevalence of 4a
      differed regionally; from 88.5% (in Sohag) to 64% (in Assuit, P = 0.002).
      Genotypes 4l and 4n had a higher prevalence in Assuit (12.8%, 10.3%) than Sohag
      (0%, 0%; P < or = 0.011). Difference in clinical features of determined
      genotypes/subtypes was observed; more carriers of non-4a variants (4l and 4n, 4f,
      or 4m) had chronic hepatitis compared to carriers of 4a (53.3% vs. 23.1%, P =
      0.025), while more patients with 4a had liver cirrhosis (45.2% vs. 13.3%, P =
      0.023). Two HCV-4o strains were isolated in this study, both from patients with
      HCC. In conclusion, geographical diversity of HCV was revealed in this study in
      southern Egypt. A further case-control study is required to confirm the trends of
      differential pathogenicity of HCV subtypes, indicated by this study.

PMID- 19382266
TI  - HCV genotypes in Sicily: is there any evidence of a shift?
AB  - The distribution of HCV strains in any area is characterized by a relative
      prevalence of one genotype, and a number of less prevalent types. In some Western
      countries a change from the prevalent HCV genotype 1 to genotypes 3 and 4 has
      been reported in the last decade. In order to assess possible variations of the
      distribution of HCV genotypes in Sicily, a southern region of Italy, a hospital
      based cohort, collected prospectively, of 3,209 subjects with chronic HCV
      infection was surveyed, comparing the distribution of HCV genotypes during two
      consecutive periods, from 1997 to 2002 and from 2003 to 2007, according to age
      and gender. The results show that genotype 1b, which has been historically the
      most prevalent in Sicily, is still predominant, followed more distantly by
      genotypes 2 and 3a. However, a cohort effect for these genotypes was seen when
      comparing the two time periods. Genotype 1b decreased slowly over the last
      decade, due to the death of the people infected, leading to a proportional
      increase of the other genotypes. No evidence was found in support of a major
      increase in the prevalence of other genotypes, such as genotype 4, in relation to
      migration patterns.

PMID- 19382267
TI  - Specific mutations in the enhancer II/core promoter/precore regions of hepatitis
      B virus subgenotype C2 in Korean patients with hepatocellular carcinoma.
AB  - Recently, hepatitis B virus (HBV) genotypes and mutations have been reported to
      be related to hepatocellular carcinoma (HCC). This cross-sectional case-control
      study examined the relationship between HCC and mutations in the enhancer II/core
      promoter and precore regions of HBV by comparing 135 Korean HCC patients infected
      with HBV genotype C2 (HBV/C2; HCC group) with 135 age-, sex-, and hepatitis B e
      antigen (HBeAg) status-matched patients without HCC (non- HCC group). Age and sex
      were also matched between HBeAg-positive and -negative patients. The prevalence
      of T1653, A1689, V1753, T1762/A1764, T1846, A1850, C1858, and A1896 mutations was
      evaluated in this population. The prevalence of the T1653 mutation in the box
      alpha region, the T1689 [corrected] mutation in between the box alpha and beta
      regions, and the T1762/A1764 mutations in the basal core promoter region was
      significantly higher in the HCC group compared to the non-HCC group (8.9% vs.
      2.2%, P = 0.017; 19.3% vs. 4.4%, P < 0.001; and 60.7% vs. 22.2%; P < 0.001).
      Among HBeAg-negative patients, the frequency of the T1653 mutation was higher in
      the HCC group. Regardless of HBeAg status, the prevalence of the T1689,
      [corrected] and T1762/A1764 mutations was higher in the HCC group than in the non
      HCC group. However, no association was observed between mutations in the precore
      region and HCC. Upon multivariate analysis, the presence of the T1653, T1689,
      [corrected] and T1762/A1764 mutations was an independent predictive factor for
      HCC. The addition of the T1653 or T1689 [corrected] mutation to T1762/A1764
      increased the risk of HCC. In conclusion, the T1653, T1689, [corrected] and/or
      T1762/A1764 mutations were associated with the development of HCC in Korean
      patients infected with HBV/C2.

PMID- 19382268
TI  - Detection and characterization of group C rotavirus in Buenos Aires, Argentina,
      1997-2003.
AB  - The role of group C rotaviruses as a cause of diarrhea was examined among
      children <17 years of age admitted to a Hospital in a suburban area of Buenos
      Aires, Argentina between 1997 and 2003. A total of 1,579 fecal samples were
      screened for group A (RVA) and C (RVC) rotaviruses by two in-house ELISA methods
      at Quilmes University (UNQ-ELISA). Samples positive, doubtful and negative by RVC
      specific UNQ-ELISA (n = 246) were examined further for RVC by another in-house
      ELISA (CDC-ELISA), electron microscopy, RT-PCR, nested PCR, and Southern
      hybridization. Sensitivity, specificity, and predictive values for each test were
      determined. While the sensitivity was comparable for the nested PCR and CDC-ELISA
      methods (82.5%), the molecular methods were slightly more specific. Poorly
      preserved particles were often seen in fecal samples, suggesting that degradation
      of RNA could be a factor influencing the performance of molecular methods. The
      incidence of RVC was estimated to be 3% without apparent differences among
      seasons. RVC infected patients had a significantly (P < 0.001) higher median age
      (6 years vs. 1 year) than those with RVA infection. Sequence of the RVC VP7 gene
      from six Argentinean strains and sequences reported previously in different
      countries showed high nucleotide (94.4-99.9%) sequence identities, indicating a
      high degree of conservation for human RVC VP7 genes among strains collected on
      five continents over a period of 17 years. These findings indicate that RVC is a
      significant cause of diarrhea and it is necessary to develop simple and sensitive
      serological methods for its detection.

PMID- 19382269
TI  - Surveillance of pathogens in outpatients with gastroenteritis and
      characterization of sapovirus strains between 2002 and 2007 in Kumamoto
      Prefecture, Japan.
AB  - Infectious acute gastroenteritis is an important public health problem worldwide.
      A total of 639 stool specimens were tested for the presence of diarrhea
      pathogens. The specimens were from outpatients with acute gastroenteritis who
      consulted the pediatric clinic in Kumamoto Prefecture, Japan, from June 2002 to
      December 2007. Of these, 421 (65.9%) were positive for diarrhea pathogens. Among
      them were norovirus (NoV) in 260 (61.8%), sapovirus (SaV) in 81 (19.2%),
      rotavirus in 49 (11.6%), adenovirus in 19 (4.5%), enterovirus in 13 (3.1%),
      astrovirus in 9 (2.1%), kobuvirus in 1 (0.2%), and bacterial pathogens in 11
      (2.6%). Mixed infection (co-infection of viruses) was found in 22 (5.2%) of the
      421 pathogen-positive stool samples. NoV was the most prevalent pathogen
      throughout the study period; however, the SaV detection rate was unexpectedly
      high and was found to be the secondary pathogen from 2005 to 2007. Genetic
      analysis of SaV with 81 strains demonstrated that SaV strains belonging to
      genogroup IV emerged in 2007, and dynamic genogroup changes occurred in a
      restricted geographic area. This study showed that SaV infection is not as rare
      as thought previously.

PMID- 19382270
TI  - Amino acid substitutions in the hepatitis C virus core region of genotype 1b are
      the important predictor of severe insulin resistance in patients without
      cirrhosis and diabetes mellitus.
AB  - Previous studies provided a direct experimental evidence for the contribution of
      HCV core protein in the development of insulin resistance (IR), but the clinical
      impact of HCV core region on IR is still not clear. The present study evaluated
      the impact of Amino acid (aa) substitutions of HCV-1b core region on IR in 123
      Japanese patients infected with HCV-1b without cirrhosis and diabetes mellitus,
      and investigated the treatment efficacy of 48-week pegylated interferon (PEG-IFN)
      plus ribavirin (RBV) according to HOMA-IR values. Patients with IR (HOMA-IR > or
      = 2.5) and severe IR (HOMA-IR > or = 3.5) were present in 51.2% and 27.6%,
      respectively. Multivariate analysis identified body mass index (> or = 25
      kg/m(2)) and hepatocyte steatosis (> or = 5%) as significant determinants of IR.
      Furthermore, multivariate analysis identified hepatocyte steatosis (> or = 5%),
      aa substitutions of the core region (Gln70 (His70) and/or Met91), and age (> or =
      55 years) as significant determinants of severe IR. Especially, significantly
      lower proportions of patients with Gln70 (His70) and/or Met91 were noted among
      those without severe IR (59.6%) than those with severe IR (82.4%). The rates of
      sustained virological response in patients with IR (50.0%) were not significantly
      different from those without IR (52.9%). Furthermore, the rates of non
      virological response in patients with IR (28.9%) were not significantly also
      different from those without IR (20.6%). In conclusion, the present study
      indicated that substitutions of HCV-1b core region were the important predictor
      of severe IR in patients without cirrhosis and diabetes mellitus, but HOMA-IR
      values might be not useful as predictors of 48-week PEG-IFN plus RBV therapy.

PMID- 19382273
TI  - Hepatitis E in Qatar imported by expatriate workers from Nepal: epidemiological
      characteristics and clinical manifestations.
AB  - Prompted by cases of acute hepatitis in expatriate workers presenting at Alkhor
      Hospital, Qatar, a limited prospective observational study was conducted from
      July 2005 to June 2006 to determine the epidemiological and clinical features of
      patients (predominantly Nepalese) presenting with acute hepatitis. Countrywide
      during that period samples from 86 Nepalese presenting at different centers were
      found to be anti-HEV IgG positive and 50 of these were also positive for anti-HEV
      IgM. Fifty-eight of those Nepalese were seen and treated at Alkhor Hospital and
      of them 43 were confirmed as cases of acute HEV, being positive for both anti-HEV
      IgM and IgG. The remaining 15 were diagnosed as probable cases of acute HEV on
      the basis of clinical and epidemiological similarity. It seems likely that
      transit in Kathmandu in reportedly unsanitary conditions was the focus of
      infection. In some of those examined at Alkhor, ultrasound detected a thickened
      gallbladder wall in 30 of 39 (76.9%) with two cases having clinical acalcular
      cholecystitis. Higher levels of alanine aminotransferase and aspartate
      aminotransferase were associated with severe disease and derangement in
      coagulation. On the available evidence hepatitis E was imported by expatriate
      workers and it is clear that medical screening of these workers pre- and post
      arrival must be improved to prevent further outbreaks. It is also essential that
      health care workers in Qatar are made aware of this ongoing problem of imported
      HEV and understand the variable presentation of the condition.

PMID- 19382274
TI  - A new isolate of hepatitis B virus from the Philippines possibly representing a
      new subgenotype C6.
AB  - Hepatitis B virus (HBV) genotypes and subgenotypes show distinct geographical
      prevalence. A genotyping analysis of 28 samples from asymptomatic HBV carriers
      from the Philippines gave a distribution of HBV genotypes as expected from a
      previous study: 54% B (15/28), C5 18% (5/28), 14% D (4/28), 7% A1 (2/28). In
      addition, 7% (2/28) of the samples showed a double infection with genotypes B and
      D. One of the isolates sequenced completely, ph105, did not group into one of the
      known subgenotypes after phylogenetic analysis. Ph105 formed a separate clade in
      genotype C. With a genome length of 3,215 nt. and a serological subtype adr,
      ph105 exhibited the main features of most genotype C strains. However, ph105
      differed by 4.1-7.2% from HBV subgenotypes C1 to C5 when comparing the nucleotide
      sequence of whole genomes. With only 4.1% difference ph105 was most closely
      related to subgenotype C2. SimPlot analysis gave no indication for recombination
      with known HBV genotypes. Ph105 fulfils all criteria for a new subgenotype C6.

PMID- 19382275
TI  - Antiviral effect of nicotinamide on enterovirus-infected human islets in vitro:
      effect on virus replication and chemokine secretion.
AB  - Type 1 diabetes is a chronic disease characterized by the selective destruction
      of insulin-producing cells in the pancreas. Enterovirus (EV) is the prime
      candidate to initiate this destruction and several inflammatory chemokines are
      induced by EV infection. Nicotinamide has been shown to protect isolated human
      islets, and to modulate chemokine expression. The aim of this study was to
      evaluate the effect of nicotinamide on EV replication and EV-induced chemokine
      secretion and cytolysis of human islets. Two EV strains were used to infect human
      islets in vitro, one lytic (Adrian) isolated from a child at onset of type 1
      diabetes, and one non-lytic (VD2921). Secretion of the chemokines IP-10 and MCP
      1, viral replication, and virus-induced cytopathic effect (CPE), were measured at
      different time points post-infection. Addition of nicotinamide to the culture
      medium reduced viral replication and virus-induced islet destruction/CPE,
      significantly. Both EV strains increased secretion of IP-10 and MCP-1, when
      measured days 2-3, and days 5-7 post infection, compared to mock-infected control
      islets. IP-10 was not produced by uninfected isolated islets, whereas a basal
      secretion of MCP-1 was detected. Interestingly, addition of nicotinamide blocked
      completely (Adrian), or reduced significantly (VD2921), the virus-induced
      secretion of IP-10. Secretion of MCP-1 was also reduced in the presence of
      nicotinamide, from infected and uninfected islets. The reported antiviral effects
      of nicotinamide could have implications for the treatment/prevention of virus-
      and immune-mediated disease. Also, this study highlights a possible mechanism of
      virus-induced type 1 diabetes through the induction of MCP-1 and IP-10 in
      pancreatic islets.

PMID- 19382276
TI  - The clinical manifestation of myocardial infarction in elderly patients.
AB  - BACKGROUND AND HYPOTHESIS: The study aimed to compare the clinical picture and
      treatment differences in elderly patients (aged 75 years or older) and younger
      patients (aged below 75 years). METHODS: The study included 80 consecutive
      patients with myocardial infarction (MI) treated in the Cardiology Ward of the
      Specialist Hospital in Radom, Poland, in 2005. Analyses were performed
      retrospectively. The patients were separated into 2 groups according to age. The
      group I study group consisted of 40 patients aged 75 or over (aged 75-95; mean 81
      years) and the group II control group consisted of 40 patients aged below 75
      years (aged 42-67; mean 60 years). RESULTS: In the elderly, as compared with
      younger subjects, dyspnea, fatigue, and other heart failure symptoms, were more
      frequently the first symptoms of MI than typical chest pain (p<0.05). ST-segment
      elevation myocardial infarction (STEMI) was also more common (p<0.05). Non-ST
      segment elevation myocardial infarction (NSTEMI) was more frequently diagnosed in
      the elderly (p<0.05). In elderly patients there were more women (p<0.05), more
      patients with previously diagnosed ischemic heart disease (p<0.05), with
      hypertension (p<0.05), and with diabetes mellitus (p<0.05). Obesity was less
      frequently diagnosed in the elderly; however the difference was not statistically
      significant. Dyslipidemia and cigarette smoking were both significantly less
      common among elderly patients (p<0.05). The elderly were significantly less
      frequently revascularized (p<0.05). Both fibrinolysis and primary percutaneous
      coronary intervention (PCI) were less commonly applied to the elderly (p<0.05).
      Time from symptom onset to hospital admission was significantly longer in the
      case of elderly patients (p<0.05). The MI complications and side effects of
      treatment seemed to be more frequent in the elderly, but only post-MI heart
      failure was observed more frequently in this group of patients (p<0.05).
      CONCLUSIONS: Our observations confirm the differences in the clinical picture of
      MI in the elderly as described previously. All patients of advanced age should be
      considered as having the highest risk of death and complications occurrence.

PMID- 19382277
TI  - Right ventricular myxoma in an asymptomatic adolescent with a history of Ewing's
      Sarcoma.

PMID- 19382278
TI  - Magnetic resonance imaging of carcinoid heart disease.
AB  - In a 56-year-old lady, a carcinoid tumor of the terminal ileum metastasized to
      regional lymph nodes, and the liver was removed by hemicolectomy in 2002.
      Following a history of cutaneous flushing, diarrhea, and bronchoconstriction 3
      years later, a somatostatin therapy was instituted. As flushing and diarrhea
      resolved and levels of urinary excretion of 5-hydoxyindoleacetic acid decreased,
      shortness of breath was progressive and prompted a cardiac exam. Despite poor
      resolution, echocardiography revealed a thickening of the tricuspid valves (TK)
      with reduced mobility along with right atrial (RA) and right ventricular (RV)
      dilatation. The pulmonary valve was unobtrusive. Magnetic resonance (MR) imaging
      revealed extensive fibrous tissue extending from the valvular base to the tip of
      the tricuspid leaflets. Retraction and immobilization of the TK caused a mild
      stenosis and a large regurgitant flow. Because medical treatment of tricuspid
      regurgitation was ineffective, the TK was excised and a Hancock 25-mm
      bioprosthetic valve was implanted. The postoperative course was uncomplicated,
      and the patient recuperated and resumed normal daily activities.

PMID- 19382279
TI  - Paclitaxel-induced ST-segment elevations.
AB  - A 51-year-old woman presented with severe chest pain minutes after starting
      intravenous paclitaxel as a part of the systemic chemotherapy due to ovarian
      carcinoma. The electrocardiogram (ECG) revealed sinus rhythm with ST-segment
      elevations in inferior and anterior leads. The ST-segment elevations resolved
      immediately after sublingual nitroglycerine. Cardiac troponin T and CPK MB levels
      remained in the normal range at repeat measurements. It was presumed that in
      spite of standard premedication, paclitaxel had induced acute coronary syndrome
      with ST-segment elevations in this patient.

PMID- 19382280
TI  - DNA, oligosaccharides, and mononucleotides stimulate oligomerization of human
      lactoferrin.
AB  - Using small-angle X-ray scattering (SAXS), light scattering (LS), and soft laser
      ablation we have shown that lactoferrin (LF) in solution at neutral pH is
      oligomerized in the absence of salt or at physiological salt concentrations. The
      level of oligomerization depends on the concentration of LF, KCl or NaCl, and on
      the duration of the protein storage in solution. At the concentrations comparable
      with those in human milk (1-6 mg/ml), the average radius of gyration (R(g))
      values of LF can attain 400-480 A, while fresh solution of previously lyophylized
      LF demonstrate a lower average R(g) (50-100 A), and R(g) value characterizing the
      LF monomer formed at 1 M NaCl is 26.7 A. The addition of oligonucleotides,
      oligosaccharides, or mononucleotides to LF in the presence or in the absence of
      KCl with different level of initial oligomerization accelerates the
      oligomerization rate and increases the R(g) values up to approximately 600-700 A,
      which correspond to associates containing ten or more protein molecules. During
      gel filtration on Sepharose 4B, high-degree LF oligomers dissociate nearly
      completely forming different degraded complexes, but in some cases it is possible
      to reveal small amount of a decamer. A possible role for oligomerization of LF, a
      highly polyfunctional protein, for its different biological activities is
      discussed.

PMID- 19382283
TI  - Retraction. Immunization with pseudotype baculovirus expressing envelope protein
      of Japanese encephalitis virus elicits protective immunity in mice by Yaoming Li,
      Jing Ye, Shengbo Cao, Shaobo Xiao, Qian Zhao, Xueqin Liu, Meilin Jin, Huanchun
      Chen.

PMID- 19382284
TI  - 31Phosphorus magnetic resonance spectroscopy study of tissue specific changes in
      high energy phosphates before and after sertraline treatment of geriatric
      depression.
AB  - INTRODUCTION: We investigated tissue specific differences in markers of energy
      metabolism, including high energy phosphate compounds (beta and total NTP, PCr)
      and pH, in older adults with depression compared with healthy controls, before
      and after a 12-week treatment trial of sertraline. METHODS: Thirteen older
      adults, age > or =55, with Major Depressive Disorder (HAMD(17) score of > or =18)
      were recruited along with ten age-matched controls. The depression subjects had a
      pre- and post-treatment 4T (31)P-MRS scan using a three-dimensional chemical
      shift imaging sequence. The extracted brain images were segmented into white
      matter (WM), gray matter (GM) and CSF. A linear mixed effects model analyzed the
      effects of pre-treatment and post-treatment depression on phosphorus metabolite
      concentration estimates (including calculated pH and Mg(++)). RESULTS: Total
      tissue beta-NTP (-8%, t(18.66) = 3.50; p = 0.0024) and total tissue total NTP (
      6%, t(17.41) = 2.68; p = 0.0156) were lower in subjects with geriatric depression
      compared with healthy controls. Total tissue levels of total-NTP changed
      significantly with treatment (-2%, t(14.84) = -2.47; p = 0.0259). Total NTP was
      reduced in the WM, but not the GM, in the pre-treatment depression group
      (t(51.65) = 4.02; p = 0.0002). Intracellular pH was higher in the GM of subjects
      with pre-treatment depression (t(1133.84) = -2.10; p = 0.0353) and decreased to
      approximate control levels after treatment (t(648.86) = -2.53; p = 0.0115).
      DISCUSSION: These findings demonstrate bioenergetic changes including tissue
      specific differences in (31)P-MRS metabolites in geriatric depression. Decreased
      white matter total NTP may reflect alterations in white matter function.

PMID- 19382285
TI  - Conservative management of spontaneous heterotopic cervical pregnancy using an
      aspiration cannula and pediatric Foley catheter.

PMID- 19382286
TI  - Post-traumatic stress disorder and prediction of aggression in persons with
      dementia.
AB  - OBJECTIVE: This prospective cohort study evaluated the potential of increased
      aggression in patients with dementia who had a preexisting diagnosis of post
      traumatic stress disorder (PTSD) compared with those without a diagnosis of PTSD.
      METHODS: Patients more than 60 years of age with newly diagnosed dementia between
      2001 and 2004 were identified from the Michael E. DeBakey Veterans Affairs (VA)
      Medical Center in Houston, TX. Among these patients, we identified patients with
      a preexisting diagnosis of PTSD. The proportions of patients who became
      aggressive within 2 years of enrollment were compared in patients with and
      without PTSD. Fisher's exact tests were used to compare differences in the number
      of PTSD patients with and without aggression. RESULTS: A total of 215 patients
      were identified with newly diagnosed dementia. Ten were found to have a diagnosis
      of PTSD, and 205 did not. Eighty-four (41%) of the 205 were found to be
      aggressive. Among the 10 patients with a diagnosis of PTSD, 4 (40%) were
      aggressive. CONCLUSION: There was no evidence to support an increased risk of
      aggression in patients with a coexisting diagnosis of dementia and PTSD.

PMID- 19382287
TI  - First-trimester uterine artery Doppler indices in the prediction of small-for
      gestational age pregnancy and intrauterine growth restriction.
AB  - OBJECTIVES: To assess the relationship of first-trimester uterine artery Doppler
      indices with subsequent delivery of small-for-gestational age (SGA) neonates or
      intrauterine growth restriction (IUGR). METHODS: This was a prospective study in
      which uterine artery Doppler assessment was performed at 11-14 weeks in 3010
      women with singleton pregnancies. Resistance indices (RI) and incidence of
      bilateral notching were compared between women with normal pregnancies (n = 2445)
      and those who delivered: SGA neonates (birth weight < 10th centile) (n = 377);
      SGA neonates who had been affected by pre-eclampsia (n = 27); IUGR neonates
      (birth weight < 10th centile and abnormal Doppler indices) with delivery > or =
      37 weeks (n = 62); and IUGR neonates requiring preterm delivery (delivery < 37
      weeks) (n = 36). RESULTS: The first-trimester uterine artery mean RI and
      prevalence of bilateral notching were significantly higher in women destined to
      deliver SGA neonates than in women with normal pregnancies (median uterine artery
      RI, 0.74 vs. 0.70, P < 0.001; prevalence of bilateral notches, 56% vs. 43%, P <
      0.001). The areas under the receiver-operating characteristics curves for the
      prediction of SGA without pre-eclampsia, IUGR, preterm IUGR and SGA with pre
      eclampsia were 0.602, 0.687, 0.776 and 0.708, respectively. There was a
      statistically significant inverse relationship between mean uterine artery RI and
      gestational age at delivery in the SGA pregnancies without pre-eclampsia (R = -
      0.329, P = 0.01). CONCLUSIONS: There is a significant relationship between first
      trimester uterine artery Doppler RI and the subsequent development of SGA. The
      sensitivity of first-trimester uterine artery Doppler is greater for SGA with pre
      eclampsia than it is for IUGR alone. This could be because these two entities may
      have different underlying placental abnormalities that are detected variably on
      first-trimester uterine artery Doppler evaluation.

PMID- 19382288
TI  - The cervical portion of the vertebral artery: a clinico-pathological study, by E.
      C. Hutchinson and P. O. Yates (from the Department of Neurology and Neuro
      pathology, the Manchester Royal Infirmary) Brain 1956: 79; 319-31 and Arterial
      occlusions in the vertebro-basilar system: a study of 44 patients with post
      mortem data, by P. Castaigne, F. Lhermitte, J. C. Gautier, R. Escourolle, C.
      Derouesne, P. Der Agopian and C. Popa (from Hopital de la Salpetriere, 47 Bd de
      l'opital, Paris, 13), Brain 1973: 96; 133-154.

PMID- 19382289
TI  - Reply: A plea for confidence intervals and consideration of generalizability in
      diagnostic studies.

PMID- 19382290
TI  - Obama administration may flat-line funding for PEPFAR.

PMID- 19382291
TI  - The drug price is right--or is it?

PMID- 19382292
TI  - Ministerial meeting agrees plan for tuberculosis control.

PMID- 19382293
TI  - Silas Weir Mitchell's The Case of George Dedlow.

PMID- 19382294
TI  - DNA damaging potential of zinc oxide nanoparticles in human epidermal cells.
AB  - At present, more than 20 countries worldwide are manufacturing and marketing
      different varieties of nanotech-based consumer products of which cosmetics form
      the largest category. Due to the extremely small size of the nanoparticles (NPs)
      being used, there is a concern that they may interact directly with
      macromolecules such as DNA. The present study was aimed to assess the
      genotoxicity of zinc oxide (ZnO) NPs, one of the widely used ingredients of
      cosmetics, and other dermatological preparations in human epidermal cell line
      (A431). A reduction in cell viability as a function of both NP concentration as
      well as exposure time was observed. ZnO NPs demonstrated a DNA damaging potential
      as evident from an increased Olive tail moment (OTM) of 2.13 +/- 0.12 (0.8 g/ml)
      compared to control 1.37 +/- 0.12 in the Comet assay after an exposure of 6 h.
      ZnO NPs were also found to induce oxidative stress in cells indicated by
      depletion of glutathione (59% and 51%); catalase (64% and 55%) and superoxide
      dismutase (72% and 75%) at 0.8 and 0.08 g/ml respectively. Our data demonstrates
      that ZnO NPs even at low concentrations possess a genotoxic potential in human
      epidermal cells which may be mediated through lipid peroxidation and oxidative
      stress. Hence, caution should be taken in their use in dermatological
      preparations as well as while handling.

PMID- 19382296
TI  - A novel role for dpp in the shaping of bivalve shells revealed in a conserved 
      molluscan developmental program.
AB  - During the molluscan evolution leading to the bivalves, the single dorsal shell
      was doubled. To elucidate the molecular developmental basis underlying this
      prominent morphological transition, we described the cell cleavage and expression
      patterns of three genes, brachyury, engrailed, and dpp in the Japanese spiny
      oyster Saccostrea kegaki, and examined the function of dpp in this species. The
      cleavage pattern of the S. kegaki embryo was nearly the same as the previously
      described pattern of other bivalve species, suggesting that the pattern itself is
      highly important for the establishment or the maintenance of the bivalve body
      plan. The expression pattern of a brachyury homolog in S. kegaki (SkBra) was
      similar to the pattern in gastopods even at the single cell level despite the
      deep divergence of gastropods and bivalves. Engrailed and dpp were previously
      found to be expressed around the shell anlagen in gastropods. Like that of
      gastropods, an engrailed homolog in S. kegaki (SkEn) was found to be expressed
      around the shell anlagen. However, the dpp homologin S. kegaki (SkDpp) was
      expressed only in the cells along the dorsal midline. ZfBMP4 treatment
      experiments revealed the importance of dpp in establishing the characteristic
      shape of the bivalve shell anlagen.

PMID- 19382295
TI  - Diverging functions of Scr between embryonic and post-embryonic development in a 
      hemimetabolous insect, Oncopeltus fasciatus.
AB  - Hemimetabolous insects undergo an ancestral mode of development in which embryos
      hatch into first nymphs that resemble miniature adults. While recent studies have
      shown that homeotic (hox) genes establish segmental identity of first nymphs
      during embryogenesis, no information exists on the function of these genes during
      post-embryogenesis. To determine whether and to what degree hox genes influence
      the formation of adult morphologies, we performed a functional analysis of Sex
      combs reduced (Scr) during post-embryonic development in Oncopeltus fasciatus.
      The main effect was observed in prothorax of Scr-RNAi adults, and ranged from
      significant alterations in its size and shape to a near complete transformation
      of its posterior half toward a T2-like identity. Furthermore, while the
      consecutive application of Scr-RNAi at both of the final two post-embryonic
      stages (fourth and fifth) did result in formation of ectopic wings on T1, the
      individual applications at each of these stages did not. These experiments
      provide two new insights into evolution of wings. First, the role of Scr in wing
      repression appears to be conserved in both holo- and hemimetabolous insects.
      Second, the prolonged Scr-depletion (spanning at least two nymphal stages) is
      both necessary and sufficient to restart wing program. At the same time, other
      structures that were previously established during embryogenesis are either
      unaffected (T1 legs) or display only minor changes (labium) in adults. These
      observations reveal a temporal and spatial divergence of Scr roles during
      embryonic (main effect in labium) and post-embryonic (main effect in prothorax)
      development.

PMID- 19382297
TI  - Clinical value of 12 occlusal features for the prediction of disc displacement
      with reduction (RDC/TMD Axis I group IIa).
AB  - The purpose of this study is to quantify the clinical value of 12 occlusal
      variables for the prediction of disc displacement with reduction diagnosed
      according to research diagnostic criteria (RDC)/temporomandibular disorder (TMD).
      Twelve occlusal features were clinically assessed by the same three operators.
      The sample consisted of 165 TMD patients (65 males, 100 females; mean age: 32.55
      +/-11.685 years) with only disc displacement with reduction (RDC/TMD Axis I group
      IIa) and a control sample of 145 healthy subjects (65 males, 80 females; mean
      age:31.24+/-12.436 years) diagnosed with RDC/TMD Axis I group 0. A stepwise
      multiple logistic regression model was used to identify the significant
      correlation between occlusal features and disease. The odds ratio for disc
      displacement was 2.84 for absence of canine guidance, 2.14 for mediotrusive
      interference and 1.75 for retruded contact position (RCP)/maximum intercuspation
      (MI) slide >or=2 mm. Other occlusal variables did not reveal to be statistically
      significant. The percentage of the total log likelihood for disc displacement
      explained by the significant occlusal factors was acceptable with a Nagelkerke's
      R(2) = 0.124. The final model including the significant occlusal features
      revealed an optimal discriminant capacity to predict patients with disc
      displacement with a sensitivity of 63.6% or with a specificity of 64.8% for
      healthy subjects and an accuracy of 64.2%. Occlusal features showed a low
      predictive value for detecting disc displacement. Multifactorial complex
      pathologies such as TMD should be investigated using a multivariate statistical
      analysis; moreover,the future of aetiopathogenic research in this matter requires
      a multifactorial approach.

PMID- 19382298
TI  - Effects of a mandibular advancement device on the upper  airway morphology: a
      cephalometric analysis.
AB  - The aims of this study were to assess changes in the upper airway morphology
      associated with an oral appliance in situ in patients suffering from the
      obstructive sleep apnoea-hypopnoea syndrome and to relate these changes to
      treatment response. Changes in upper airway morphology as a result of an oral
      appliance were assessed in 52 patients with obstructive sleep apnoea-hypopnoea
      syndrome by means of cephalometric analysis. Lateral cephalograms were taken at
      baseline and after 2-3 months of treatment. Baseline and follow-up cephalograms
      were traced twice and cephalometric variables were compared. The predictive value
      of changes in upper airway morphology for the treatment response was evaluated in
      univariate and multivariate regression analyses. Oral appliance therapy resulted
      in an increased posterior airway space at the level of the second vertebra, the
      uvular tip and the base of the tongue. The increase of the posterior airway space
      at the level of the second vertebra and the uvular tip were the best predictors
      for relative improvement of the apnoea-hypopnoea index. However, the predictive
      value for treatment response of these cephalometric upper airway changes should
      be interpreted with caution.

PMID- 19382299
TI  - fMRI study of brain activity elicited by oral parafunctional  movements.
AB  - Parafunctional masticatory activity, such as the tooth clenching and grinding
      that is associated with bruxism, is encountered by clinicians in many
      disciplines, including dentistry, neurology and psychiatry. Despite this, little
      is known about the neurological basis for these activities. To identify the brain
      network engaged in such complex oromotor activity, functional magnetic resonance
      imaging (fMRI) was used to elucidate the brain activation patterns of 20
      individuals (10 males and 10 females, mean s.d. age of 26.3+/-4.1 years) with
      (parafunctional, PFx group, 5M/5F) and without (normal functional, NFx group, 5
      M/5F) self-reported parafunctional grinding and clenching habits during clenching
      and grinding tasks. Subject group classification was based on: (i) self-reported
      history, (ii) clinical examination, (iii) evaluation of dental casts and (iv)
      positive responses to the temporomandibular disorder (TMD) History Questionnaire
      [Dworkinand LeResche, Journal of Craniomandibular Disorders, (1992) 6:301]. While
      subjects performed these oromotor tasks, each wore a custom-designed oral
      appliance minimizing head motion during imaging. Mean per cent signal changes
      showed significant between group differences in motor cortical (supplementary
      motor area, sensorimotor cortex and rolandic operculum) and subcortical (caudate)
      regions. Supplementary motor area data suggest that motor planning and
      initiation, particularly during the act of clenching, are less prominent in
      individuals with oromotor parafunctional behaviours. The overall extent of
      activated areas was reduced in subjects with self-reported parafunctional
      masticatory activity compared with the controls. This study's methodology and
      findings provide an initial step in understanding the neurological basis of
      parafunctional masticatory activities that are relevant for therapeutic research
      applications of temporomandibular joint and muscle disorders and associated
      comorbidities.

PMID- 19382300
TI  - Retraction. Uncoupling IL-2 signals that regulate T cell proliferation, survival,
      and Fas-mediated activation-induced cell death.

PMID- 19382301
TI  - Antinuclear antibody positivity in patients with chronic hepatitis C: clinically
      relevant or an epiphenomenon?
AB  - BACKGROUND: Serum autoantibodies such as antinuclear antibody (ANA) are
      frequently detected in patients with chronic hepatitis C virus (HCV) infection,
      but its relevance is a matter of discussion. AIM: To assess the association of
      ANA positivity with clinical and histological features, and with the outcome of
      antiviral therapy in patients with HCV infection. METHODS: Baseline samples from
      patients with hepatitis C treated with interferon and ribavirin were tested for
      ANA positivity by indirect immunofluorescence. RESULTS: The mean age was 48.3+/
      11.1 years and 56% were men. Among 234 included patients, 22 patients (9.4%) were
      positive for ANA. These patients showed significantly higher median alanine
      aminotransferase level (3.52 vs. 2.39 x upper limit of normal, P=0.009) when
      compared with ANA-negative patients. Fibrosis stage and necroinflammatory grading
      were not influenced by ANA positivity. Sustained virological response (SVR) rates
      were similar between ANA-positive and ANA-negative patients (27 vs. 29%,
      P=0.882). Alanine aminotransferase flares (> or =1.5-fold the baseline) during
      treatment were observed in 28 patients (12%), irrespective of the presence of ANA
      and without any clinical significance. CONCLUSION: Among HCV patients, ANA
      positivity seems to represent an immunological epiphenomenon. It neither
      influences clinical, biochemical, and histological features of chronic hepatitis
      C nor predicts response to antiviral treatment.

PMID- 19382302
TI  - Management of late biliary complications in patients with gallbladder stones in
      situ after endoscopic papillary balloon dilation.
AB  - OBJECTIVE: Patients with untreated gallbladder stones in situ are at high risk
      for late biliary complications after endoscopic papillary balloon dilation (EPBD)
      and bile duct stone extraction. Few data exist on the short-term and long-term
      results in these patients after the recurrence of bile duct stones and acute
      cholecystitis. The aim of this study was to evaluate the outcome of late biliary
      complications in patients with gallbladder stones in situ after EPBD. METHODS:
      Fifty-six patients who developed late biliary complications, including bile duct
      stone recurrence (n=43) and acute cholecystitis (n=13), were managed at our
      institutions. We investigated the short-term and long-term outcomes after the
      management of late biliary complications. RESULTS: Complete removal of recurrent
      bile duct stones was achieved in 38 of 43 patients (88%) by repeated EPBD alone.
      Pancreatitis after repeated EPBD occurred in two patients (5%). After successful
      bile duct stone extraction by EPBD, none of the 16 patients who underwent
      cholecystectomy developed late biliary complications (mean follow-up period of
      5.2 years), whereas re-recurrent bile duct stones occurred in three of the 21
      patients (14%) with gallbladder stones left in situ (mean follow-up period of 4.4
      years)(P=0.1148). Re-recurrent bile duct stones were successfully treated
      endoscopically. One of the eight patients who did not undergo cholecystectomy for
      acute cholecystitis had a recurrence of cholecystitis, which was managed
      conservatively. CONCLUSION: The long-term outcomes of late biliary complications
      are favorable when patients with concomitant gallbladder stones undergo
      cholecystectomy. Re-recurrent bile duct stones are considerable when gallbladder
      stones are left in situ, but should be treated endoscopically.

PMID- 19382303
TI  - Stuart Green's Vignettes 15 and 16.

PMID- 19382304
TI  - Serum chromogranin A reflects regression of metastatic   carcinoid during
      prolonged octreotide treatment.

PMID- 19382305
TI  - European dissent over GM crops.
AB  - The European Union has failed to quell the revolt among its member states over
      the union-wide acceptance of GM crops. Soon the four rebels could gain Germany as
      a new ally.

PMID- 19382306
TI  - The growing GM   challenge.
AB  - Frustration at the public resistance to GM crops in Europe is leading to
      campaigns to highlight future developments.

PMID- 19382307
TI  - Lethal troubles.
AB  - The battle for whale conservation is intensifying ahead of a key meeting in June.

PMID- 19382308
TI  - Taking off.
AB  - The world's largest parrot has proved a conservation challenge.

PMID- 19382309
TI  - Breakthroughs and blind ends.
AB  - Evolution of a through gut with an oral and an anal opening conceivably marked a
      breakthrough in early animal history, as basal animals have a blind ending gut
      with only one opening. How this occurred, and whether a through gut evolved only
      once or several times is a matter of debate. Perhaps the different modes by which
      guts develop in animal embryos that are used for the classification of animals
      can shed some light on this question.

PMID- 19382310
TI  - Darwin's continental drift.
AB  - Lisbon is grandly celebrating the Darwin anniversaries, but to the east in Turkey
      things are different.

PMID- 19382311
TI  - Putative neuronal mechanisms of sensitive skin.
AB  - According to epidemiological studies, up to 50% of adults report facial
      sensitivity with various distinctive symptoms, such as prickling, burning,
      tingling, pain or itching. This is termed sensitive skinand represents a syndrome
      of physiological reactions rather than a disease entity. In this review, we
      discuss the currently available literature on this syndrome and describe the
      possible underlying neuronal pathomechanisms. The sensory receptors expressed on
      unmyelinated nerve fibres and keratinocytes involved in nociception, such as
      TRPV1 and endothelin receptors, are hypothesized to play a role in the induction
      of sensitive skin. Furthermore, we discuss the role of neurotrophins and the
      influence of stress on sensitive skin.

PMID- 19382312
TI  - Q&A: Susan Mango.
AB  - Susan Mango is Benning Professor of Oncological Sciences at the University of
      Utah and an Investigator at the Huntsman Cancer Institute. She grew up in England
      and Washington D.C. before attending Harvard University. She received her Ph.D.
      from Princeton, where she studied the c-myc oncogene with Michael Cole. She was
      introduced to the nematode Caenorhabditis elegans as a postdoc with Judith Kimble
      at the University of Wisconsin - Madison, and moved to Utah in 1996 to start her
      own lab. After 13 years at the University of Utah, she will move to Harvard
      University in July 2009. Her principal focus is transcriptional strategies of
      organ development, using the C. elegans foregut as a model.

PMID- 19382313
TI  - Opioids and the skin--where do we stand?
AB  - The common ectodermal origin of the skin and nervous systems can be expected to
      predict likely interactions in the adult. Over the last couple of decades much
      progress has been made to elucidate the nature of these interactions, which
      provide multidirectional controls between the centrally located brain and the
      peripherally located skin and immune system. The opioid system is an excellent
      example of such an interaction and there is growing evidence that opioid
      receptors (OR) and their endogenous opioid agonists are functional in different
      skin structures, including peripheral nerve fibres, keratinocytes, melanocytes,
      hair follicles and immune cells. Greater knowledge of these skin-associated
      opioid interactions will be important for the treatment of chronic and acute pain
      and pruritus. Topical treatment of the skin with opioid ligands is particularly
      attractive as they are active with few side effects, especially if they cannot
      cross the blood-brain barrier. Moreover, cutaneous activation of the opioid
      system (e.g. by peripheral nerves, cutaneous and immune cells, especially in
      inflamed and damaged skin) can influence cell differentiation and apoptosis, and
      thus may be important for the repair of damaged skin. While many of the pieces of
      this intriguing puzzle remain to be found, we attempt in this review to weave a
      thread around available data to discuss how the peripheral opioid system may
      impact on different key players in skin physiology and pathology.

PMID- 19382314
TI  - Murine mast cells secrete a unique profile of cytokines and prostaglandins in
      response to distinct TLR2 ligands.
AB  - Mast cells (MCs) are important effector cells in host defense against bacteria.
      In the course of a bacterial infection, MCs can be activated by various
      mechanisms, i.e. bacterial toxins, endogenously produced infection-associated
      peptides or via complement receptors, fimbrial adhesion molecules and toll-like
      receptors (TLRs). While some of these mechanisms are well established, the
      effects of TLR2 ligand-driven MC activation are far less understood. Here, we
      show that murine mature connective tissue-type MCs, but not immature bone marrow
      derived cultured mast cells, express significant amounts of full length TLR2 on
      their surface. Activation by various TLR2 ligands only induces the selective
      release of cytokines in peritoneum-derived cultured mast cells (PCMCs) with
      preferential secretion of pro-inflammatory cytokines (IL-6 > IL-17 > IFN-gamma
      TNF > IL-1 > GM-CSF) upon stimulation with lipoteichoic acid (LTA). This response
      is much lower in PCMCs stimulated with the TLR2/6 agonist macrophage-activating
      lipopeptide-2 (MALP-2), which most prominently triggers the release of the
      immunomodulatory cytokine IL-10. Furthermore, only LTA but not MALP-2 induces
      prostaglandin D2 secretion which is again restricted to the mature MC phenotype.
      These findings suggest that TLR2 ligand-mediated activation of mature MCs, i.e.
      tissue-residing cells, which most likely occurs during infection, can selectively
      raise a potent inflammatory or anti-inflammatory response, depending on TLRs
      which are engaged.

PMID- 19382315
TI  - Valproate-induced reversible pseudoatrophy of   the brain and hyperammonemic
      encephalopathy   in a bipolar patient.

PMID- 19382316
TI  - Mast cells: novel clinical perspectives from recent insights.
AB  - Mast cells are still generally viewed as mediators of type I allergic or
      pseudoallergic reactions. Research over the past 10 years revealed that our view
      was too small and that mast cells are of key importance in innate immunity and
      also types II, III and IV adaptive immune reactions. Understanding their role in
      modulating and amplifying of inflammatory responses provides important insights
      into the pathogenesis of skin diseases such as psoriasis, atopic dermatitis,
      bullous pemphigoid or the control of infections. This helps us to understand the
      course of these diseases, their trigger mechanisms, and, the new role of agents,
      which can modulate the function of mast cells. These insights will help to
      develop new therapeutic approaches.

PMID- 19382317
TI  - Referral and resource use patterns for psychiatric-related visits to pediatric
      emergency departments.
AB  - OBJECTIVE: To describe the patterns of referral and use of resources for patients
      with psychiatric-related visits presenting to pediatric emergency departments
      (EDs) in a pediatric research network. METHODS: We conducted a retrospective
      chart review of a random sample of patients (approximately 10 charts per month
      per site) who presented with psychiatric-related visits in 2002 to 4 pediatric
      EDs in the Pediatric Emergency Care Applied Research Network. Emergency
      department resource use variables evaluated included the use of consultation
      services, restraints, and laboratory tests as well as ED length of stay. RESULTS:
      We reviewed 462 patient visits with a psychiatric-related ED diagnosis. Mean (SD)
      age was 12.8 (3.7) years, 52% were male, and 49% were African American. The most
      common chief complaints were suicidality (47%), aggression/agitation (42%), and
      anxiety/depression (27%), alone or in combination. Ninety percent of patients
      (range across sites, 83%-94%) had a mental health consult in the ED, 5% were
      restrained (range, 3%-9%), and 35% had a laboratory test performed (range, 15%
      63%). Mean (SD) ED length of stay was 5.1 (5.4) hours, and 52% were admitted (93%
      to a psychiatric bed, including transfers to separate psychiatric facilities).
      CONCLUSIONS: Children with psychiatric-related visits seem to require substantial
      ED resources. Interventions are needed to reduce the burden on the ED by
      increasing the linkage to mental health services, particularly for suicidal
      youths.

PMID- 19382318
TI  - The utility of bedside ultrasonography in identifying fractures and guiding
      fracture reduction in children.
AB  - OBJECTIVE: To compare bedside ultrasonography (BUS) to radiography for
      identifying long bone fractures, the need for reduction, and the adequacy of
      reduction. METHODS: Children aged 2 to 17 years presenting to a pediatric
      emergency department with long bone injuries were prospectively enrolled. Bedside
      ultrasonography was performed before ordering initial radiographs. If a fracture
      was identified, measurements of angulation and displacement were made based on
      BUS images. Radiographs were used to guide management. Patients who had a
      fracture identified on radiograph underwent standard care. Later, agreement
      between BUS and radiography for fracture identification, the need for reduction,
      and the adequacy of reduction were determined. RESULTS: Thirty-three patients
      were enrolled, the mean age was 9.1 years (+/-3.1 years). Sixty six bones were
      studied; 56 (84.8%) involved the upper extremity. Fractures were identified in
      59.1% of all bones; 13 (33.3%) required reduction.The agreement between BUS and
      radiography for fracture identification was 95.5%, for the need for reduction
      92.3%, and for the adequacy of reduction 92.3%. The sensitivity and specificity
      of BUS for fracture identification, need for reduction and reduction adequacy was
      0.97 (95% confidence interval [CI], 0.85-1.00), 0.93 (95% CI, 0.74-0.99), and
      1.00 (95% CI 0.79-1.00), and 0.85 (95% CI, 0.61-0.96), 1.00 (95% CI, 0.59-1.00)
      and 0.80 (95% CI, 0.30-0.99), respectively. CONCLUSIONS: These data suggest that
      BUS evaluation of upper extremity injuries not involving joints maybe comparable
      to radiography for identifying fractures, the need for reduction, and the
      adequacy of reduction in children. If further investigations which include a
      larger number of lower extremity, growth plate, and joint injuries support our
      findings, BUS may gain a more prominent role in managing children with all long
      bone injuries.

PMID- 19382319
TI  - Management of occult fractures in the skeletally immature patient: cost analysis
      of implementing a limited trauma magnetic resonance imaging protocol.
AB  - STUDY OBJECTIVE: Fractures in children may not be visible in the result of
      initial radiography, and undertreatment and overtreatment of such fractures
      routinely occur. The purpose of this study was to evaluate the potential cost of
      implementing limited magnetic resonance imaging (MRI) at initial encounter, when
      radiographs are unrevealing. METHODS: This was a retrospective review of 204
      emergency department pediatric patients presenting between January 1, 2005 and
      February 28, 2006 with appendicular trauma, with initially negative radiographic
      result and follow-up. Emergency department treatment categorization of (1) no
      treatment, (2) ACE wrap, (3) brace, (4) splint, or (5) casting was evaluated.
      Final determination of presence or absence of fracture was based on follow-up.
      Patients with fractures were considered undertreated when they received
      categories 1 to 3 care; patients without fractures were considered overtreated
      when they received categories 4 and 5 care. The percentage of patients
      undertreated or overtreated and direct and total costs were determined and
      analyzed in conjunction with the cost of a limited MRI at initial encounter.
      Total costs include direct and indirect costs (lost wages for each day off work
      for the parent). Cost estimates assume patients determined to be without
      fractures at follow-up will not return for follow-up clinical care or obtain
      additional imaging after MRI at initial encounter. RESULTS: Twenty-eight (13.7%)
      of the 204 patients had fractures at follow-up. Fifty one percent of patients
      without fractures were overtreated; 29% with fractures were undertreated. Mean
      direct cost for all patients and cost estimation with limited MRI protocol were
      $843.81 and $891.79, respectively (P = 0.365). However, mean total cost for all
      patients and cost estimation with limited MRI protocol was $1059.49 and $929.10,
      respectively (P = 0.02). CONCLUSIONS: Based on clinical grounds and initially
      negative radiographic results, slightly more than half of patients without
      fractures can be overtreated, and nearly one third of patients with fractures can
      be undertreated. Instituting a protocol that includes limited trauma MRI lowers
      the total cost of care without increasing direct cost, and appropriate care may
      be instituted at the outset.

PMID- 19382320
TI  - Assisted birth with DISC1.

PMID- 19382321
TI  - Parental knowledge and perceptions of fever in children and fever management
      practices: differences between parents of children with and without a history of
      febrile seizures.
AB  - OBJECTIVES: The aim of this study was to compare maternal knowledge and
      perceptions of fever, fever management practices, and information sources of
      mothers of children with and without a history of febrile seizures. METHODS: A
      questionnaire was used to survey mothers of children who visited health
      departments for a routine 18-month-old well baby check-up. RESULTS: A total of
      386 responses were analyzed. More mothers of children with a history of febrile
      seizures than mothers of children without it stated that high fever caused
      febrile seizures and antipyretics prevented it. Fewer mothers of children with a
      history of febrile seizures than mothers in the other group thought that high
      fever caused brain damage and antipyretics prevented the disease from worsening
      and warmed the child's body during fever episode. Many mothers in both groups
      stated that they considered physicians to be their primary information source.
      Spouse and own parents were named as information sources among mothers of
      children with a history of febrile seizures, whereas books and the Internet were
      named in the other group. CONCLUSIONS: Mothers of children with a history of
      febrile seizures demonstrated a higher rate of accuracy in their knowledge of
      fever than those in the other group. Mothers of children with a history of
      febrile seizures used personal communication, whereas those in the other group
      relied on mass communication for health information. Providing accurate
      information to family members is essential to provide mothers with both accurate
      information and emotional support.

PMID- 19382322
TI  - Take your pick.

PMID- 19382323
TI  - Spreading it thick.

PMID- 19382324
TI  - Revisiting predictors of parental health care-seeking behaviors for nonurgent
      conditions at one inner-city hospital.
AB  - INTRODUCTION: To determine important predictors of why parents seek care for
      their children at a pediatric emergency department (ED) compared to their child's
      primary care provider's (PCP's) walk-in clinic. DESIGN: Cross-sectional study.
      SETTING: An inner-city hospital located in New York City, from April 2003 to
      January 2004. PARTICIPANTS: A convenience sample of 170 parents with children
      younger than 18 years, Medicaid beneficiaries, had a PCP, and presented with a
      nonurgent medical problem either at the pediatric ED or walk-in clinic. MAIN
      OUTCOME MEASURE: The main outcome measure was the setting in which parents sought
      care for their child; odds ratios (ORs) were calculated for parents seeking care
      in the pediatric ED compared to those seeking care at the walk-in clinic,
      adjusting for predisposing, enabling, and need-related factors. RESULTS: Of the
      170 parent-child visits, 87 (51%) were seeking care at the ED and 83 (49%) at
      their child's walk-in clinic. In logistic regression, single parenting was the
      strongest predictor for seeking care in the ED (OR, 5.54; 95% confidence interval
      [CI], 1.4-26.9), followed by Hispanic ethnicity (OR, 4.96; 95% CI, 1.43-17.2),
      low parental perceptions of their child's physical health (OR, 0.90; 95% CI, 0.82
      0.99), controlling for number of chronic conditions, parental working status, and
      satisfaction with their PCP. CONCLUSIONS: Single parenting, Hispanic ethnicity,
      and perceptions of health are associated with health care-seeking behaviors in
      high cost settings among Medicaid beneficiaries. Targeted education programs
      could be used to influence future site of care.

PMID- 19382325
TI  - Exerting self-control for persistence.

PMID- 19382326
TI  - Wnts and motor neuron destiny.

PMID- 19382327
TI  - Committing to a break up.

PMID- 19382328
TI  - Amyloid-beta and PrPC: it takes two.

PMID- 19382329
TI  - What brings newborns to the emergency department?: a 1-year study.
AB  - AIMS: Characterization of newborn visits to the pediatric emergency department
      (PED). Analysis of the main illnesses and establishment of association between
      certain conditions and severity of diseases. METHODS: Retrospective study
      information concerning newborns (aged <28 days) who presented to the PED of
      Hospital Central de Faro during 2005. We studied the clinical and demographic
      data referring to the PED's episode and to perinatal occurrences. RESULTS: A
      total of 540 neonates visited the PED (1.5% of the total PED use), with an
      average age of 14.0 days and a slight prevalence of males (53.1%). Of the total
      visits, 17.2% were primary physician referrals. The chief complaints were
      jaundice, excessive crying, and rash. Diagnostic tests were requested in 27.2%
      cases. The major diagnoses were nonapparent disease, infant colics, and
      physiologic jaundice. In 13.0%, hospital admission was necessary. Newborns with
      referral, those with less than 37 weeks of gestation and those whose delivery
      weight was less than 2500 g, were more likely to be admitted. CONCLUSIONS: Most
      PED visits were because of nonserious diseases, mainly because of insufficient
      caretaker knowledge and information. This highlights the great need for
      caretakers' education by health staff. It is also important that physicians are
      aware of the main illnesses in the newborn period and know how to correctly
      identify the conditions associated to serious pathology.

PMID- 19382330
TI  - An intimate relationship.

PMID- 19382331
TI  - Personnel dilemma.

PMID- 19382332
TI  - Comparison of fatty acid, mineral and proximate composition of body and legs of
      edible frog (Rana esculenta).
AB  - The fatty acid profile and mineral composition (calcium, magnesium, sodium,
      phosphorus, potassium, iron, zinc, manganese, silicon, boron, cadmium, chromium,
      nickel, aluminium, copper, and lead) by Inductively Coupled Plasma-Atomic
      Emission Spectometry (ICP-AES) and the proximate composition of the body and legs
      of edible frog (Rana esculenta) were investigated. The fatty acids occurring in
      the highest proportions in both the body and leg of frogs were mystiric acid
      (C14:0, 1.13-2.30%), palmitic acid (C16:0, 19.76-23.23%), stearic acid (C18:0,
      3.61-6.29%), palmitoleic acid (C16:1, 7.06-13.08%), oleic acid (C18:1n-9 cis,
      10.83-16.71%), linoleic acid (C18:2n-6, 6.44-6.71%), gamma-linolenic (C18:3n-6,
      0.13-0.27%), linolenic (C18:3n-3, 2.32-3.37%), cis-11,14,17-eicosatrienoic acid
      (C20:3n-3, 4.71-7.72%), cis-5,8,11,14,17-eicosapentaenoic acid (C20:5n-3, 3.96
      6.05%) and cis-4,7,10,13,16,19-docosahexaenoic acid (C22:6n-, 2.77-6.67%). Among
      the minerals determined, potassium was found to be highest, followed by
      phosphorus. Calcium, aluminium, cadmium, copper, lead, chromium, nickel, boron,
      silicon and zinc are found to be lower than the potential toxicity levels.

PMID- 19382333
TI  - Comparison of fatty acid and proximate compositions of the body and claw of male
      and female blue crabs (Callinectes sapidus) from different regions of the
      Mediterranean coast.
AB  - Fatty acid and proximate compositions of the body and claw of male and female
      blue crabs from Akyatan Lagoon and Hurma strait were investigated. Male blue crab
      meat had a higher protein and fat content, and lower moisture and ash content,
      than that of the female from Akyatan Lagoon. Moreover, there were variations of
      protein and fat amounts in both female crab meats between Akyatan Lagoon and
      Hurma strait. The dominant saturated fatty acids were palmitic acid (16:0; range
      from approximately 12% to 15%) and stearic acid (18:0; range from approximately
      7.5% to 16.1%) for all samples. The total monounsaturated fatty acid content in
      the body of female crabs from Akyatan Lagoon was higher than those of Hurma
      Strait (22.04% versus 7.55%). There were no statistically significant differences
      (P>0.05) between eicosapentaenoic acid concentrations in body meat of the male
      crab than those of female crab meat from Akyatan Lagoon (P<0.05). Docosahexaenoic
      acid contents were different between the body meat of male crabs from Akyatan
      Lagoon and those of female crabs from Hurma strait. The total n3 was detected as
      27.33% in body meat whereas it was 24.39% in claw meat of the male crab from
      Akyatan Lagoon. Those values were almost similar in the body and claw meat of
      female crab from Akyatan Lagoon.

PMID- 19382334
TI  - Extraction and identification of cyclobutanones from irradiated cheese employing
      a rapid direct solvent extraction method.
AB  - 2-Alkylcyclobutanones (cyclobutanones) are accepted as chemical markers for
      irradiated foods containing lipid. However, current extraction procedures
      (Soxhlet-florisil chromatography) for the isolation of these markers involve a
      long and tedious clean-up regime prior to gas chromatography-mass
      spectrophotometry identification. This paper outlines an alternative isolation
      and clean-up method for the extraction of cyclobutanones in irradiated Camembert
      cheese. The newly developed direct solvent extraction method enables the
      efficient screening of large numbers of food samples and is not as resource
      intensive as the BS EN 1785:1997 method. Direct solvent extraction appears to be
      a simple, robust method and has the added advantage of a considerably shorter
      extraction time for the analysis of foods containing lipid.

PMID- 19382336
TI  - Fatty acid and amino acid composition of raw and hot smoked sturgeon (Huso huso,
      L. 1758).
AB  - Changes in fatty acid and amino acid composition in hot smoked sturgeon (Huso
      huso, L. 1758) were studied. The sturgeon was smoked for 20 min at 30 degrees C,
      followed by 90 min at 50 degrees C and 40 min at 80 degrees C. The palmitic acid
      (C16:0) and stearic acid (C18:0) increased (P<0.05) from 17.70% to 27.52% and
      from 7.49% to 13.63% after smoking, respectively. The oleic acid content in
      smoked sturgeon decreased from 28.29% to 25.93%, but no change (P>0.05) was
      observed in the total monounsaturated fatty acid composition of fish after
      smoking. Total polyunsaturated fatty acid, eicosapentaenoic acid and
      docosahexaenoic acid contents decreased from 21.03% to 4.93%, from 4.65% to 0.49%
      and from 12.41% to 0.51% in sturgeon after smoking, respectively. The total n-3
      and n-6 contents and the n-3/n-6 ratio of raw and smoked sturgeon were 17.48
      1.35, 3.54-3.58 and 4.94-0.38, respectively. The atherogenic index and index of
      thrombogenicity values of raw and smoked sturgeon were determined as 1.01-0.31
      and 1.93-1.24, respectively. The smoking process caused an increase (P<0.05) in
      aspartic acid >isoleucine >methionine >hidoksil-1-proline >valine, and a decrease
      (P<0.05) in glutamic acid >serine >threonine >leucine >tyrosine >histidine
      >lysine >proline. However, the changes in alanine, glycine and phenylalanine were
      insignificant (P>0.05).

PMID- 19382335
TI  - Fatty acid composition of salami from different countries and their nutritional
      implications.
AB  - 'Milano-type' salami from 13 European and American countries were analysed to
      establish their nutritional value in relation to fat and fatty acid composition.
      The fat content, fatty acid profile, ratio of n-6/n-3 polyunsaturated fatty
      acids, ratio of hypocholesterolemic/hypercholesterolemic fatty acids (h/H) and
      the contribution to the daily intake recommended for the population were studied.
      Differences (P<0.05) in the dry matter, pH, water activity, fat content, and
      percentages of saturated, monounsaturated and polyunsaturated fatty acids were
      found. Principal component analysis permitted samples to be separated into three
      different groups: (1) salamis from Chile, Mexico and Brazil, with high n-6/n-3
      ratios (14-16), medium iodine index (73-76) and high h/H ratios (2.6-2.7); (2)
      European salamis and salamis from Costa Rica and USA, with medium and high n-6/n
      3 ratios (8-15), low iodine index (62-72) and low h/H ratios (2.1-2.6); and (3)
      products from Peru, with the lowest n-6/n-3 ratio (7.2), the highest iodine index
      (about 80) and medium h/H ratio (2.5).

PMID- 19382337
TI  - Chemical and nutritional changes associated with the development of the hard-to
      cook defect in common beans.
AB  - Four common bean (Phaseolus vulgaris L.) varieties, Kawanda (K)131, K132, NABE4
      and NABE11, were evaluated for the relationship between development of the hard
      to-cook (HTC) defect and changes in nutritional quality during 6-month storage
      under ambient conditions. All varieties developed the HTC defect, but the extent
      was found to vary with variety. Cooking time increased by 113% in K131, 95.3% in
      K132, 56.4% in NABE4 and 42.93% in NABE11 after 6 months. The development of the
      HTC defect was found to be associated with a reduction in phytic acid content (r2
      = -0.802), in vitro protein digestibility (r2 = -0.872) and in vitro starch
      digestibility (r2 = -0.729). The susceptibility to the HTC defect during storage
      could be attributed to a phytic acid interaction with proteins and carbohydrates,
      and is also associated with small seed size. Breeding for large seed size could
      therefore help reduce the development of the HTC defect.

PMID- 19382338
TI  - Spectroscopic investigation of the seeds of chilli (Capsicum annum L.).
AB  - In addition to their use as food and spice, chillies have been popular in both
      Ayurvedic and homoeopathic treatments since ancient times. Elemental analyses on
      their seeds with the help of X-ray fluorescence spectra reveal the presence of
      hitherto undetected magnesium, along with sulphur and chlorine. Fourier transform
      infrared and Fourier transform Raman spectra of the seeds reveal the presence of
      specific functional groups, attributed to the different bands present in the
      spectra. Ascorbic acid, reported to be the vitamin present in maximum amount in
      chilli peppers, is conspicuous by its absence in the seeds.

PMID- 19382339
TI  - What quality award winners do to spark improvements in the OR.

PMID- 19382340
TI  - Is propylene oxide induced cell proliferation in rat nasal respiratory epithelium
      mediated by a severe depletion of water-soluble non-protein thiol?
AB  - Propylene oxide (PO) concentrations >or=300 ppm induced cell proliferation and
      tumors in rat nasal respiratory epithelium (NRE). Cell proliferation was
      suggested to result from depletion of glutathione (GSH) in NRE. In order to
      substantiate this hypothesis, cell proliferation - measured by bromodeoxyuridine
      incorporation into DNA of the epithelium lining middle septum, dorsal medial
      meatus, and medial and lateral surfaces of the nasoturbinate in transverse nasal
      sections taken immediately posterior to the upper incisor teeth - and water
      soluble non-protein thiol (NPSH) in NRE were determined after exposing male
      Fischer 344 rats to 50 ppm, 100 ppm, 200 ppm, or 300 ppm PO (6 h/day, 3 days).
      Both parameters were also investigated after treating rats for 3 days with
      diethylmaleate (DEM; 2 x 250 mg/kg/day or 500 + 150 mg/kg/day) or buthionine
      sulfoximine (BSO; 500 mg/kg/day). Exposure to 50 ppm PO and treatment with 2 x2
      50 mg/kg/day DEM resulted in NPSH levels approximating 50% and 80% of the level
      in untreated controls, respectively. Cell proliferation did not increase. After
      exposures to >or= 100 ppm PO or treatment with BSO or 500 + 150 mg/kg/day DEM,
      NPSH was depleted to <or=1/3 of the control level and cell proliferation
      increased 2.0-3.7-fold the control value. In conclusion, profound perturbation of
      the GSH status may represent a crucial step in PO induced rat nasal
      tumorigenicity.

PMID- 19382341
TI  - Cadmium exposure disrupts GABA and taurine regulation of prolactin  secretion in
      adult male rats.
AB  - This work was undertaken to evaluate the possible effects of cadmium exposure on
      24 h changes of gamma-aminobutyric acid (GABA) and taurine median eminence and
      pituitary contents. Also the possible alterations of the regulatory mechanisms of
      GABA and taurine on prolactin secretion were evaluated. Adult male rats were
      given cadmium at a dose of 25 mg/l of cadmium chloride in the drinking water for
      30 days. Control age-matched rats received cadmium free water. Metal exposure
      induced the appearance of a maximal value of prolactin at 08:00 h. In median
      eminence, cadmium abolished the GABA and taurine maximal values and decreased
      GABA and taurine mean levels. In the anterior pituitary, cadmium treatment phase
      advanced 12 h the peak observed in controls at 00:00 h for both amino acids.
      There was a positive correlation between GABA and taurine contents in median
      eminence and the anterior pituitary in both control and cadmium-exposed animals.
      However, the correlation between GABA or/and taurine with prolactin levels
      disappeared in cadmium-exposed animals. These results suggest that cadmium
      exposure affects GABA and taurine daily pattern in the median eminence and
      anterior pituitary, and those changes explain, at least in part, the modification
      in the regulatory pattern of prolactin secretion.

PMID- 19382342
TI  - Evaluation of a psychoeducational intervention for adolescents with inflammatory
      bowel disease.
AB  - OBJECTIVES: Inflammatory bowel disease (IBD), comprising Crohn's disease,
      ulcerative colitis, and indeterminate colitis, often has its onset in
      adolescence. The aim of this study was to evaluate whether a psychoeducational
      group intervention (aiming to enhance information seeking and giving about the
      disease, relaxation, social competence, and positive thinking) can strengthen the
      coping efforts of adolescents with IBD and have a positive effect on their Health
      Related Quality of Life (HRQoL). METHODS: Adolescent IBD patients from the Emma
      Children's Hospital AMC and adolescent members of the Crohn and Ulcerative
      Colitis Association in The Netherlands, were invited to participate in The
      intervention study. Using reliable and valid self-report instruments the
      adolescent's coping styles, feelings of competence, and HRQoL were assessed
      before and 6-8 months after the intervention. The parents were asked to fill in
      the Child Behavior Check List. Linear regression analyses were performed to test
      whether group participation was predictive of the outcome measures while
      correcting for the first measurement occasion and sex. RESULTS AND CONCLUSION:
      Forty patients responded positively to invitation to the intervention. Eighteen
      adolescents, however, lived too far away to attend and served as a control group.
      Twenty-two children were enrolled and attended in groups of four to six children
      in six group sessions, supervised by two psychologists. The intervention seemed
      to have a positive effect on: coping (predictive control, P<0.01), feelings of
      competence (global self-worth, P<0.05 and physical appearance, P<0.01), and HRQoL
      (body image, P<0.05). These results give good reason to continue this
      intervention study with a larger population.

PMID- 19382343
TI  - Gastrointestinal symptoms in patients with liver cirrhosis are linked to impaired
      quality of life and psychological distress.
AB  - INTRODUCTION: The factors that lead to an impaired quality of life (QoL) in
      patients with liver cirrhosis are incompletely understood. Gastrointestinal (GI)
      symptoms are frequent in liver cirrhosis and are known to reduce QoL in GI and
      non-GI diseases. AIMS: To study the possible association of GI symptoms with QoL
      and psychological distress in patients with liver cirrhosis. METHODS: Seventy
      five consecutive outpatients with liver cirrhosis received validated
      questionnaires to assess GI symptoms, QoL, anxiety, depression, and neuroticism.
      GI symptoms were considered as relevant when they occurred often over the last 12
      months (more than 3 months total), were at least moderately severe and/or led to
      consultation of a physician. An association of GI symptoms with QoL and
      psychological scores was ascertained by logistic regression analysis before and
      after adjusting for age and sex. RESULTS: Eighty percent of patients had one or
      more relevant GI symptoms. Physical component of QoL correlated negatively with
      Child-Pugh scores (P<0.01), whereas no association between mental component of
      QoL and Child-Pugh scores was detectable (P=0.4). Both dimensions of QoL
      decreased significantly with increasing numbers of GI symptoms reported by the
      patients (physical component: P<0.001; mental component: P<0.01). Number of GI
      symptoms was also significantly related to poorer anxiety, depression, and
      neuroticism scores. CONCLUSION: GI symptoms are linked to QoL and psychological
      distress in patients with liver cirrhosis.

PMID- 19382344
TI  - Relative adrenal insufficiency in a patient with liver disease.
AB  - Patients with established cirrhosis are at increased risk of sepsis. Bacterial
      infections are a frequent cause of morbidity and mortality in patients with
      advanced liver disease. Mortality for patients admitted to hospital with
      bacterial infection is approximately 30%, whereas the development of septic shock
      and multiorgan failure is associated with a mortality of 70-100%. Activation of
      the hypothalamic-pituitary-adrenal axis is an important feature of a patient's
      response to severe sepsis and major trauma. An inadequate adrenal response with
      suboptimal cortisol production has been recognized in patients with septic shock.
      Patients with septic shock and adrenal insufficiency have reduced response to
      vasoconstrictor agents, higher rates of refractory shock and high mortality
      rates. An improvement in survival with administration of hydrocortisone in
      patients with septic shock and an inadequate adrenal response has been
      demonstrated. In a more recent study, however, there was no survival benefit in
      septic shock though reversal of shock was faster with hydrocortisone
      administration. Recently, adrenal insufficiency has been demonstrated in patients
      with severe liver disease such as acute liver failure, acute on chronic liver
      failure, recent liver transplantation and cirrhosis irrespective of the presence
      of sepsis. Nevertheless survival benefit with administration of hydrocortisone
      has only been demonstrated in patients with cirrhosis and septic shock. A case
      report of a patient with cirrhosis and adrenal insufficiency is presented with a
      review of the literature.

PMID- 19382345
TI  - Time-resolved OH-->EH transition of the aberrant ba3 oxidase from Thermus
      thermophilus.
AB  - The kinetics of single-electron injection into the oxidized nonrelaxed state (OH 
      -> EH transition) of the aberrant ba3 cytochrome oxidase from Thermus
      thermophilus, noted for its lowered efficiency of proton pumping, was
      investigated by time-resolved optical spectroscopy. Two main phases of
      intraprotein electron transfer were resolved. The first component (tau
      approximately 17 mus) reflects oxidation of CuA and reduction of the heme groups
      (low-spin heme b and high-spin heme a3 in a ratio close to 50:50). The subsequent
      component (tau 420 mus) includes reoxidation of both hemes by CuB. This is in
      significant contrast to the OH--> EH transition of the aa3-type cytochrome
      oxidase from Paracoccus denitrificans, where the fastest phase is exclusively due
      to transient reduction of the low-spin heme a, without electron equilibration
      with the binuclear center. On the other hand, the one-electron reduction of the
      relaxed O state in ba3 oxidase was similar to that in aa3 oxidase and only
      included rapid electron transfer from CuA to the low-spin heme b. This indicates
      a functional difference between the relaxed O and the pulsed OH forms also in the
      ba3 oxidase from T. thermophilus.

PMID- 19382346
TI  - Comparison of biochemical composition of three aqua cultured fishes
      (Dicentrarchus labrax, Sparus aurata, Dentex dentex).
AB  - The moisture, ash, protein and fat content and amino acid, fatty acid and mineral
      compositions in the flesh of three commercially important fish species
      (Dicentrarchus labrax, Sparus aurata, Dentex dentex) from the aqua culture of
      Turkey were evaluated. Ranges of moisture, ash, protein and fat contents were
      69.68-76.42%, 1.49-1.95%, 18.21-21.70% and 2.29-8.10%, respectively. Among them,
      those occurring in the highest proportions were aspartic acid (3238.91-5204.71
      mg/100 g), glutamic acid (5256.60-5810.43 mg/100 g), arginine (198.07-414.91
      mg/kg), phenylalanine (50.51-386.96 mg/100 g), leucine (375.84-574.94 mg/100 g)
      and lysine (3089.71-4711.98 mg/100 g). The fatty acid compositions of sea bass
      (D. labrax), sea bream (S. aurata) and common dentex (D. dentex) ranged from
      28.01% to 32.41% saturated, from 25.88% to 28.62% monounsaturated, and from
      24.75% to 27.42% polyunsaturated. The highest potassium, magnesium, phosphorus,
      iodine and selenium contents were found in these fishes.

PMID- 19382347
TI  - Biochemical composition of some red and brown macro algae from the Northeastern
      Mediterranean Sea.
AB  - Proximate analysis and the fatty acid profile of brown algae (Stypopodium
      schimperii) and red algae (Spyridia filamentosa, Acanthophora nayadiformis and
      Halymenia floresii) were investigated. The highest protein content was obtained
      from H. floresii (3.05% on a dry weight basis) whereas the lowest protein content
      was obtained from S. schimperii (1.12% dry weight). The lipid content of macro
      algae ranged from 1.10% for S. filamentosa to 11.53% dry weight for S.
      schimperii. The ash content of all algae species were found to be high (17.98
      27.15%) on a dry weight basis. The fatty acid compositions of macro algae species
      were in the range 29.92-68.93% saturated, 17.88-39.23% monounsaturated and 6.0
      17.57% polyunsaturated acids. Among them, those occurring in the highest
      proportions were palmitic acid (C16:0, 28.36-64.67%), myristoleic acid (C14:1,
      5.54-6.7%), palmitoleic acid (C16:1, 3.33-19.51%), oleic acid (C18:1n9 cis, 6.62
      13.92%), linoleic acid (C18:2n6, 1.03-4.65%), arachidonic acid (C20:4n6, 1.2
      6.9%), and cis-5,8,11,14,17-eicosapentaenoic acid (C20:5n3, 1.07-9.89%).
      According to results obtained from this study, these macro algae species can be
      regarded as a potential source for food or the neutraceutical industry.

PMID- 19382348
TI  - Persimmon cv. Hachiya (Diospyros kaki Thunb.) fruit: some physical, chemical and
      nutritional properties.
AB  - The persimmon cv. Hachiya (Diospyros kaki) fruits were analysed for some physical
      properties (fruit dimensions, fruit mass, fruit volume, fruit density, aspect
      ratio, geometric mean diameter, sphericity, spread area, projected area, bulk
      density, skin and flesh firmness, skin and flesh colour as L, a and b values,
      coefficient of static friction on different surfaces and porosity), chemical
      properties (moisture, ash, pH, acidity, vitamin C, total soluble solids) and
      nutritional properties (phosphorus, potassium, calcium, magnesium, sodium, iron,
      manganese, copper and zinc). The fruit characteristics ranged from 169 g for
      average fruit mass, 65.97 mm for the geometric mean diameter, 1.03% for
      sphericity and 180 cm3 for volume of fruit. The bulk density, fruit density and
      porosity were determined as 5,817 N/m3, 9,300 N/m3 and 38.06%, respectively. The
      present study also revealed important nutritional values of persimmon fruits.

PMID- 19382349
TI  - Chemical compositions and antioxidant properties of essential oils from nine
      species of Turkish plants obtained by supercritical carbon dioxide extraction and
      steam distillation.
AB  - Chemical compositions and antioxidant activities of essential oils from nine
      different species of Turkish plants, namely Melissa officinalis L., Rosmarinus
      officinalis L., Cuminum cyminum L., Piper nigrum L., Lavandula stoechas spp.,
      Foeniculum vulgare, Pimpinella anisum L., Thymus serpyllum and Liquidamber
      orientalis Mill., were studied. Essential oils were obtained by supercritical
      carbon dioxide (SCCO2) extraction and steam distillation, and were analyzed by
      gas chromatography-mass spectrometry. The antioxidant activities of SCCO2
      extraction and steam distillation extracts were tested by means of the 1,1
      diphenyl-2-picrylhydrazyl (DPPH) assay. Essential oils extracted by SCCO2 and
      steam distillation showed different compositions in different species. In the
      DPPH assay, R. officinalis, C. cyminum, P. anisum, T. serpyllum and L. orientalis
      essential oils obtained by SCCO2 extraction showed higher antioxidant activity
      than steam distillation extracts, with radical scavenging activities ranging from
      87.1 +/- 0.23% to 92.0 +/- 0.34% compared with the butylated hydroxytoluene
      positive control (91.4 +/- 0.21%).

PMID- 19382350
TI  - Determination of antioxidant effects of some plant species wild growing in
      Turkey.
AB  - In this study, the antioxidant activity of 50% aqueous methanol extracts of
      Crataegus tanacetifolia (Lam.) Pers, Crataegus bornmuelleri Zaberi, Crataegus
      orientalis Pall. ex M.Bieb. var. orientalis, Crataegus szovitsii Pojark,
      Crataegus curvisepala Lindm., Crataegus monogyna Jacq. subsp. monogyna, Crataegus
      monogyna Jacq.subsp. azarella (Gris.) Franco, Crataegus micophylla C.Koch, Rosa
      foetida Herrm., Rosa hemisphaerica J.Herrm., Rosa pulverulenta M.Bieb., Rosa
      canina L., Rubus discolor Weihe & Nees, Rubus canescens DC. var. canescens, Rubus
      sanctus Screber, Rubus caesius L., Sorbus umbellata (Desf.) Fritsch var.
      umbellata, Prunus avium L. (Moench.) and Prunus cerasus L. Mespilus germenica was
      evaluated by various antioxidant assays, including free radical scavenging,
      hydrogen peroxide scavenging and metal-chelating activities. The extracts of R.
      hemisphaerica J.Herrm., P. cerasus L. and R. canina L. showed more stronger free
      radical scavenging and hydrogen peroxide scavenging activities, and the extracts
      of R. foetida Herrm. (62.54%) and P. cerasus L. showed stronger metal-chelating
      activity. The results obtained in the present study indicated that the R.
      hemisphaerica J.Herrm., P. cerasus L. and R. canina are potential sources of
      natural antioxidant. These antioxidant properties depend on the concentration of
      the sample.

PMID- 19382351
TI  - Comparison of the mineral and trace element concentrations between 'gazpacho' and
      the vegetables used in its elaboration.
AB  - Contents of moisture, ash and minerals and trace elements (sodium, potassium,
      calcium, magnesium, iron, copper, zinc and manganese) were determined in
      vegetable samples--garlic, tomato, white onion, cucumber, pepper--in 'gazpacho',
      which was elaborated using these vegetables. The mean sodium concentration in
      'gazpacho' was much higher than those mean values observed in the fresh
      vegetables. The mean values of the minerals studied in the 'gazpacho', except
      sodium and calcium, tend to be lower than the mean values in the vegetables used.
      Garlic presented significantly higher mean contents of the trace elements than
      the rest of the vegetables and the 'gazpacho'. Many highly significant
      correlations between all the minerals analyzed, except calcium, were observed.
      Factor analysis makes it possible to differentiate the samples of garlic, onion,
      and 'gazpacho' from one another, and from the rest of the vegetables considered.

PMID- 19382352
TI  - Global.  20th anniversary of World AIDS day marks progress, no solution.

PMID- 19382353
TI  - Treatment.  Study: AIDS drugs might trigger diabetes.

PMID- 19382354
TI  - Sentencing.  HIV-positive man's drug regimen excludes him from drug court.

PMID- 19382355
TI  - Prevention.  United Nations: women need empowerment to fight AIDS.

PMID- 19382356
TI  - Pandemic.  Activists call for national AIDS strategy from new president.

PMID- 19382357
TI  - Employment.  Employee's retaliation suit over HIV disclosure fails.

PMID- 19382358
TI  - HIV-positive man denied supplemental SSI benefits.

PMID- 19382359
TI  - Disclosure.  HIV-positive man's invasion of privacy claim fails.

PMID- 19382360
TI  - Bias.  Study: HIV doctors subconsciously favor whites.

PMID- 19382361
TI  - HIV treatment costs balloon for clinics as funding remains flat. ART costs are
      the highest, research shows.

PMID- 19382362
TI  - Bureaucracy creates huge burden for HIV clinics. Study details hidden costs to
      providers.

PMID- 19382363
TI  - Adherence can cause increase in direct ART and health care costs. Study
      highlights short-term impact.

PMID- 19382364
TI  - New female condom clears FDA committee. Next for FDA review: package label and
      insert.

PMID- 19382365
TI  - Better than nothing: keeping pts on failing regimen has benefits.
AB  - In a retrospective study of HIV-infected patients, those with CD4+ lymphocyte
      count 50-200, and < 50 who had detectable HIV RNA levels on combination
      antiretroviral therapy (cART), a 34% and 22% reduction, respectively, in new AIDS
      defining events (ADE) was observed in patients who continued cART compared to
      patients who stopped cART.

PMID- 19382366
TI  - FDA notifications. FDA grants approval for raltegravir.

PMID- 19382367
TI  - [A bloody boldness: amputations of the neck of the womb in France at the
      beginning of the 19th century].
AB  - During the 1820s and 1830s the number of uterus cervix amputations increases in
      France, becoming a speciality for some famous surgeons such as Jacques Lisfranc.
      Since the end of the 1820s, however, the operation is known as useless and
      dangerous by specialists, and censured in medical papers. Why did Lisfranc carry
      on operating? This paper tries to clear up the intricate reasons of this success
      and this passion, by exploring the scientific and technical context, but also the
      social and professional struggles in the rising art of 19th-century surgery.
      Thus, it attempts to understand how therapeutic choices or medical practices can
      be constructed.

PMID- 19382368
TI  - Using Cardicor as first-line therapy in heart failure : CiBis iii.

PMID- 19382369
TI  - [On bourgeoisie and electors: observations on the case of Tuscany].

PMID- 19382370
TI  - [Lucca and Florence: the Lucchesi knights of Santo Stefano in the Medicean era].

PMID- 19382371
TI  - [Aspects and juridical problems of the survival of public use statutes in Tuscany
      in the modern and contemporary eras].

PMID- 19382372
TI  - A diagnostic flowchart, including TCD, Xe-CT and angiography, to improve the
      diagnosis of vasospasm critically affecting cerebral blood flow in patients with
      subarachnoid haemorrhage, sedated and ventilated.
AB  - The aim of this study was to prospectively evaluate a clinical protocol including
      transcranial doppler (TCD), Xenon-CT (Xe-CT) and angiography, for the detection
      of vasospasm leading to critical reductions of regional cerebral blood flow
      (rCBF) in both ventilated and sedated SAH patients, i.e. patients in whom
      clinical evaluation was not possible. Seventy-six patients were prospectively
      included in a surveillance protocol for daily TCD vasospasm monitoring. When TCD
      showed a V(mean) above 120 cm/sec in the middle cerebral artery (MCA), patients
      underwent Xe-CT study. If rCBF in the MCA was reduced to below 20 ml/100 g/min or
      if there was a reduction in the rCBF with significant asymmetry between the two
      MCAs, angiography was performed. Conversely, further Xe-CT and angiography were
      not obtained unless the TCD V(mean) values reached values above 160 cm/sec. In 35
      patients, V(mean) attained values above 120 cm/sec, but only in five of them,
      rCBF was suggestive of vasospasm, and angiography confirmed the diagnosis in
      four. The protocol suggests that in sedated and ventilated patients, detection of
      a critical rCBF reduction due to vasospasm is possible to allow for more specific
      treatment and to reduce undue medical complications.

PMID- 19382373
TI  - [Vine and wine in history and in law from the 11th to the 19th centuries].

PMID- 19382374
TI  - [Posterior cerebral vasospasm following subarachnoid hemorrhage. Correlation by
      transcranial Doppler and perfusion CAT].

PMID- 19382375
TI  - [Acetylsalicylic acid does not prevent progression of primary circulatory
      disorders in patients without symptoms of arterial disease and diabetes--POPADAD
      trial].

PMID- 19382376
TI  - [Small dose of acetylsalicylic acid is not effective in prevention of primary
      atheromatous incidents in patients with type 2 diabetes--JPAD trial].

PMID- 19382377
TI  - [The 2nd Conference of the Working Group of Sport Cardiology of Polish Cardiac
      Society/The 3rd Olympic Day of Cardiology--3rd December 2008--a report].

PMID- 19382378
TI  - [Where are we in treatment of stable coronary disease--commentary on treatment
      RECENT].

PMID- 19382379
TI  - "Vague sense of belonging to the Russian Empire": the reindeer Chukchi's status
      in nineteenth century northeastern Siberia.

PMID- 19382380
TI  - Team work: do we "walk the walk" or just "talk the talk?".

PMID- 19382382
TI  - The integrative role of seals in an East Greenlandic hunting village.

PMID- 19382381
TI  - Temporally restricted role of retinal PACAP: integration of the phase-advancing
      light signal to the SCN.
AB  - Circadian rhythms in physiology and behavior are temporally synchronized to the
      day/night cycle through the action of light on the circadian clock. In mammals,
      transduction of the photic signal reaching the circadian oscillator in the
      suprachiasmatic nucleus (SCN) occurs through the release of glutamate and
      pituitary adenylate cyclase-activating peptide (PACAP). The authors' study aimed
      at clarifying the role played by PACAP in photic resetting and entrainment. They
      investigated the circadian response to light of PACAPnullmice lacking the 5th
      exon of the PACAP coding sequence. Specifically, they examined free-running
      rhythms, entrainment to 12-h light:12-h dark (LD)cycles, the phase-response curve
      (PRC) to single light pulses, entrainment to a23-h T-cycle, re-entrainment to 6-h
      phase shifts in LD cycles, and light-induced c-Fos expression. PACAP-null and
      wild-type mice show similar free-running periods and similar entrainment to 12:12
      LD cycles. However, the PRC of PACAP-null mice lacks a phase-advance portion.
      Surprisingly, despite the absence of phase advance to single light pulses, PACAP
      null mice are able to entrain to a 23-h T-cycle, but with a significantly longer
      phase angle of entrainment than wild types. In addition, PACAP-null mice re
      entrain more slowly to a 6-h phase advance of the LD cycle. Nevertheless,
      induction of c-Fos by light in late night is normal. In all experiments, PACAP
      null mice show specific behavioral impairments in response to phase-advancing
      photic stimuli. These results suggest that PACAP is required for the normal
      integration of the phase advancing light signal by the SCN.

PMID- 19382383
TI  - "Whose colour was not black nor white nor grey, but an extraneous mixture, which
      no pen can trace, although perhaps the pencil may": Aspasie and Delacroix's
      "Massacres at Chios".

PMID- 19382384
TI  - Dead animals and the beast machine: seventeenth-century Netherlandish paintings
      of dead animals, as anti-cartesian statements.

PMID- 19382385
TI  - Aestheticizing the ancestral city: antiquarianism, topography and the
      representation of London in the long eighteenth century.

PMID- 19382386
TI  - [Bites by venomous snakes: epidemiologic panorama in Mexico].

PMID- 19382387
TI  - Outbreak of intra-hospital acquired rotavirus in a pediatric hospital in Mexico.

PMID- 19382388
TI  - University of Pennsylvania Oral and Maxillofacial Surgery  Training Program.

PMID- 19382389
TI  - Peripheral visions: alternative aspects and rural presences in mid-eighteenth
      century London.

PMID- 19382390
TI  - "Beastly sights": the treatment of animals as a moral theme in representations of
      London, c. 1820-1850.

PMID- 19382391
TI  - Government and the metropolitan image: ministers, Parliament and the concept of a
      capital city, 1840-1915.

PMID- 19382392
TI  - Informed consent to donate embryos for research purposes.

PMID- 19382393
TI  - Nelarabine: new drug. T-lymphoblastic leukaemia/lymphoma: more evaluation needed.
AB  - 1) Acute T-lymphoblastic leukaemia and T-lymphoblastic lymphoma are closely
      related malignant haemopathies. There is a better prognosis for children with
      these disorders than for adults. There is no consensus treatment in case of
      relapses. However, only haematopoietic stem cell transplantation following
      chemotherapy offers a chance of long-term survival; 2) Nelarabine is a purine
      analogue closely related to clofarabine, fludarabine and cytarabine. It is
      marketed for the treatment of children and adults with one or the other of these
      two malignant haemopathies, after failure of at least two lines of chemotherapy;
      3) Clinical evaluation of nelarabine in this setting includes two non-comparative
      trials in accordance with the conditions of the marketing terms, one in 48
      children and the other in 28 adults. A complete haematological response was
      observed in about 20% to 25% of patients overall. But this type of non
      comparative trial cannot demonstrate whether a specific drug increases survival
      time compared with existing alternatives; 4) In addition to haematological and
      gastrointestinal disorders, the main adverse effects of nelarabine were
      neurological (headache, drowsiness, peripheral neuropathies). Some adverse
      effects were serious, and they did not all resolve after treatment cessation. It
      is not known to what extent they affect quality of survival; 5) In practice,
      there are too many outstanding questions to determine whether nelarabine
      represents a therapeutic advance compared with clofarabine, or even whether it
      should be used outside the clinical trial setting.

PMID- 19382394
TI  - Piranesi and Francesco Bianchini: "capricci" in the service of pre-scientific
      archaeology.

PMID- 19382395
TI  - Despoiled at the source.

PMID- 19382396
TI  - The matchless beauty of widowhood: Vittoria Colonna's reputation in nineteenth
      century England.

PMID- 19382397
TI  - "She was cut out for this work": Ella Odstedt, woman and researcher.

PMID- 19382398
TI  - Dexrazoxane: new indication. Anthracycline extravasation: continue using dimethyl
      sulfoxide.
AB  - 1) Anthracycline extravasation can provoke extensive tissue necrosis, sometimes
      with serious consequences. Topical dimethylsulfoxide (DMSO) is the main antidote
      known to prevent this necrosis. It is used off-licence in France, based on the
      results of non-comparative trials. Among nearly 150 patients treated with
      dimethylsulfoxide, only one required surgery and about 10% of patients had
      sequelae; 2) A product based on dexrazoxane, an iron chelator, also approved to
      prevent anthracycline cardiotoxicity, has now been authorized for intravenous
      treatment of anthracycline extravasation; 3) Clinical evaluation of dexrazoxane
      in this setting does not include any trials versus dimethylsulfoxide. The
      combination of dexrazoxane plus dimethylsulfoxide is contraindicated, based on
      the results of animal studies; 4) Clinical evaluation of dexrazoxane only
      includes one case of anthracycline extravasation from a central venous line; 5)
      In two non-comparative trials in a total of 54 patients, only one patient
      required surgery for tissue necrosis. About one-third of patients had local
      complications (sensory disorders, pain, cutaneous atrophy, or restricted
      movement); 6) The only known adverse effect of topical dimethylsulfoxide is local
      irritation. In contrast, 10% of patients who received intravenous dexrazoxane had
      an infection that the investigators considered possibly linked to dexrazoxane. In
      addition to the known haematological effects of dexrazoxane (leukopenia and
      thrombocytopenia), other serious adverse events observed in the two trials
      included a major increase in hepatic transaminase activity, elevated creatinine
      levels, and hyper- or hypokalaemia; 7) Based on an evaluation that is neither
      sufficiently thorough nor rigorous, the risk-benefit balance of intravenous
      dexrazoxane appears to be less favourable than that of local dimethylsulfoxide,
      which should therefore continue to be used in this setting. In the meantime,
      preventive measures should be strictly followed in order to prevent extravasation
      from occurring. The assessment of dexrazoxane in anthracycline extravasation from
      a central line also remains inadequate.

PMID- 19382399
TI  - Albumin-bound paclitaxel: new drug. Breast cancer metastases: no progress.
AB  - Albumin-bound paclitaxel has no tangible advantages over standard paclitaxel, but
      it may provoke more adverse effects.

PMID- 19382400
TI  - Lapatinib: new drug. For some women with metastatic breast cancer.

PMID- 19382401
TI  - Bevacizumab in kidney cancer: new indication. Premature approval of this
      indication.
AB  - Only one comparative clinical trial; major protocol modifications to improve
      trial results; no clear evidence of a survival benefit; too many adverse effects.

PMID- 19382402
TI  - Comparative study for the postoperative analgesic efficacy of 20 mL at 0.5, 0.75,
      and 1% ropivacaine in posterior brachial plexus block.
AB  - BACKGROUND AND OBJECTIVES: Arthroscopic shoulder surgeries are associated with
      severe postoperative pain. Among the analgesic techniques available, brachial
      plexus block has the best results. The objective of this study was to determine
      which concentration of local analgesic used in the posterior brachial plexus
      block provides longer postoperative analgesia. METHODS: Ninety patients
      undergoing posterior brachial plexus block were randomly divided into three
      groups of 30 patients each. Group 1: 20 mL of 0.5% ropivacaine; Group 2: 20 mL of
      0.75% ropivacaine; and Group 3: 20 mL of 1% ropivacaine. The blockade was
      evaluated by assessing the thermal sensitivity using a cotton pad with alcohol
      and postoperative pain was evaluated according to a Verbal Numeric Scale (VNS) in
      the first 48 hours. RESULTS: Postoperative analgesia was similar in all three
      groups according to the parameters evaluated: mean VNS, time until the first
      complaint of pain, and postoperative opioid consumption. CONCLUSIONS: This study
      demonstrated that posterior brachial plexus block provides effective analgesia
      for shoulder surgeries. Twenty milliliters of ropivacaine in the different
      concentrations used in this study promoted similar analgesia.

PMID- 19382403
TI  - Influence of tracheal gas insufflation during capnography in anesthetized
      patients.
AB  - BACKGROUND AND OBJECTIVES: Tracheal gas insufflation (TGI) consists in injecting
      gas in the trachea (usually oxygen). is used in patients with acute respiratory
      distress syndrome (ARDS) to reduce capnometry. In Anesthesiology, the reduction
      in capnometry can be useful, but there are no studies on the reduction in
      capnometry using TGI. The objective of this study was to evaluate the changes
      caused by TGI on capnometry in anesthetized patients. METHODS: Eleven patients,
      ages 18 to 60 years, ASA I or II, without lung diseases were evaluated
      prospectively. After tracheal intubation, a TGI catheter was inserted 2 to 3 cm
      from the carina. Patients underwent volume-controlled ventilation. The volumetric
      capnography curve was recorded during 20 minutes and blood was drawn to determine
      the PaCO2. Twenty minutes after TGI was instituted, the capnograph curve was
      recorded and blood was drawn once more to measure PaCO2. The end-tidal partial
      pressure of CO2(P(ET)CO2) and PaCO2 were evaluated before and after TGI. The
      capnography curve was observed before and during TGI. RESULTS: PaCO2 and P(ET)CO2
      without TGI were: 33.48 +/- 6.81 and 36.91 +/- 6.54 mmHg (mean +/- standard
      deviation), respectively, and after TGI, 33.85 +/- 8.31 and 36.55 +/- 7.93 mmHg,
      respectively. Parameters were not statistically different before and after TGI,
      both for PaCO2 and P(ET)CO2 (p = 0.65 and 0.82). The capnography curve showed
      changes in alveolar air during expiration. CONCLUSIONS: The use of TGI did not
      result in a reduction in PaCO2 or P(ET)CO2 but it altered the morphology of the
      capnography curve.

PMID- 19382404
TI  - Complications and prognosis of intraoperative blood transfusion.
AB  - BACKGROUND AND OBJECTIVES: Intraoperative blood transfusions are associated with
      an increase in postoperative complications and hospital costs. Thus, this study
      evaluated the characteristics, complications, and probable risk factors for death
      in surgical patients who needed intraoperative blood transfusions. METHODS: This
      is a prospective study that spanned a one-year period, undertaken at the surgical
      suite of a tertiary hospital. Patients older than 18 years who needed
      intraoperative blood transfusions were included in this study Jehovah witnesses,
      patients with a history of prior blood transfusions, coronary failure, and acute
      brain lesions were excluded. RESULTS: Eighty patients with mean age of 68.4 +/-
      14.1 years participated in the study. Most patients were ASA II, representing
      69.6% of the study group; APACHE and POSSUM scores were 13.6 +/- 4.4 and 37.5 +/-
      11.4, respectively. Mean hemoglobin at the time of transfusion was 8.2 +/-1.8 g x
      dL(-1) and 19% of the patients had hemoglobin levels higher than 10 g x dL(-1).
      Patients received an average of 2.2 +/- 0.9 IU of packed red blood cells.
      Hospital mortality was 26.3%. Post-transfusion complications totaled 57.5% of the
      cases in the postoperative period, and most of them were due to infections. In
      the logistic regression, independent factors for death included APACHE II (OR =
      1.34; 95% CI 1.102-1.622), POSSUM (OR = 1.08; 95% CI 1.008-1.150) and the number
      of packed red blood cells received (OR = 2.22; 95% CI 1.100-4.463). Thus, the
      higher the number of transfusions, the greater the incidence of complications and
      mortality. CONCLUSIONS: Hemoglobin level, and the number of packed red blood
      cells used were elevated when compared with studies that suggest restrictive
      strategies. This sample presented a high incidence of complications, especially
      infections, and complications. APACHE II and POSSUM scores and the number of
      transfusions were independent risk factors for a worse postoperative prognosis.

PMID- 19382405
TI  - Incidence and prophylaxis of nausea and vomiting in post-anesthetic recovery in a
      tertiary teaching hospital.
AB  - BACKGROUND AND OBJECTIVES: Postoperative nausea and vomiting (PONV) is frequent
      and potentially a severe complication that increases the length of anesthetic
      recovery and causes patient dissatisfaction. The evaluation of the risk of PONV
      and institution of prophylactic measures aiming the well-being of patients and
      cost reduction are frequent in the medical literature. This observational study
      evaluated the incidence, risk factors, and adjustment and effectivity of the
      prophylaxis of PONV in the recovery room of a tertiary teaching school. METHODS:
      Information obtained from patients' records and questionnaires answered by
      patients included age, major predictive factors for PONV (female gender, history,
      absence of smoking, and postoperative use of opioids), prophylactic drugs
      administered, development of PONV type of surgery and anesthesia, use of nitrous
      oxide, clinical status, and length of stay in the recovery room. RESULTS: An
      incidence of 18.5% of nausea and 8.5% of vomiting in the immediate postoperative
      period was observed. A correlation between major risk factors and the development
      of PONV was also observed. A correlation between those factors and prophylactic
      anti-emetic drugs, as well as between their use and the development of PONV, was
      not observed. However, a tendency to administer prophylactic medication to young
      female patients was observed. CONCLUSIONS: The concerns of the anesthesiologists
      of the institution with PONV were evident. However, the absence of correlation
      between risk and prophylaxis suggests an empirical and ineffective procedure.
      Factors that were not evaluated were suggested by the absence between PONV and
      the use of antiemetic drugs. The orientation for anesthesiologists regarding more
      effective prophylactic measures can improve care of the population assisted.

PMID- 19382406
TI  - Effects of peritoneal lavage with bupivacaine on survival of mice with fecal
      peritonitis.
AB  - BACKGROUND AND OBJECTIVES: Based on the knowledge of the anti-inflammatory and
      anti-bacterial actions of local anesthetics (LA), the objective of this study was
      to determine the effects of peritoneal lavage with bupivacaine on survival of
      mice with fecal peritonitis. METHODS: Forty-eight Wistar mice, weighing between
      300 and 330 g (311.45 +/- 9.67 g), undergoing laparotomy 6 hours after induction
      of peritonitis were randomly divided in 4 groups: 1--Control, without treatment
      (n = 12); 2--Drying of the abdominal cavity (n = 12); 3--Lavage with 3 mL NS and
      posterior drying of the abdominal cavity (n = 12); and 4--Lavage with 8 mg x kg(
      1) (+/- 0.5 mL) of 0.5% bupivacaine added to 2.5 mL of NS followed by drying out
      of the abdominal cavity (n = 12). Animals that died underwent necropsy and the
      time of death was recorded. Surviving animals were killed on the 11th
      postoperative day and underwent necropsy. RESULTS: Group 1 presented a 100%
      mortality rate in 52 hours, 100% mortality rate in Group 2 in 126 hours, and
      Group 3 presented a 50% mortality rate in 50 hours. Animals in Group 4 survived.
      Survival on the 11th day was greater in groups 3 and 4 than in Groups 1 and 2 (p
      < 0.001) and greater in Group 4 than in Group 3 (p< 0.01). CONCLUSIONS:
      Peritoneal lavage with a solution of bupivacaine diluted in NS was effective in
      preventing death for 11 days in 100% of animals with fecal peritonitis.

PMID- 19382407
TI  - Ultrasound-guided sciatic-femoral block for revision of the amputation stump.
      Case report.
AB  - BACKGROUND AND OBJECTIVES: The use of ultrasound in regional blocks has become
      increasingly used because its role as facilitator and its efficacy. Direct
      ultrasound visualization allows the identification of peripheral nerves,
      independently of the ability of obtaining sensitive or motor stimulation. CASE
      REPORT: This is the case of a patient who underwent revision of the amputation
      stump at the knee under ultrasound-guided sciatic-femoral block with 40 mL of
      0.5% ropivacaine, promoting complete sensitive blockade and excellent surgical
      anesthesia. CONCLUSIONS: Ultrasound assistance is capable of amplifying the
      spectrum of uses of peripheral nerve blocks in surgical interventions on
      amputated limbs in situations neurostimulation cannot be used.

PMID- 19382408
TI  - Pseudothrombocytopenia in a patient undergoing splenectomy of an accessory
      spleen. Case report.
AB  - BACKGROUND AND OBJECTIVES: Coagulation tests (CBC and prothrombin time) were
      initially conceived as a mean of screening and following rare congenital
      coagulopathies; the CBC provides the number of platelets per cubic milliliter.
      The objective of this report was to present the case of a patient who presented
      with an extremely low number of platelets when her blood was analyzed in an EDTA
      containing tube and its numbers were normal when the blood was analyzed with
      citrate, alerting for the risk of erroneously administering blood products. CASE
      REPORT: This is the case of a 40-year-old female patient, ASA II. In 2001 she
      presented with thrombocytopenia and was referred to a hematologist in Manaus, in
      the state of Amazonas, Brazil and underwent splenectomy that same year with a
      diagnosis of idiopathic thrombocytopenic purpura. Since her CBCs continued to
      show thrombocytopenia, an abdominal ultrasound was done and showed a spherical
      hypoechoic image, with an echotexture similar to the spleen, measuring 2.0 x 1.7
      cm, with well-defined contents (accessory spleen), and a splenectomy was
      indicated. One hour into the surgery, blood samples were drawn for CBC and
      chemistry: Hb = 11.3 g x dL(-1); Ht = 33.4%; Platelets = 35,000 microL(-1); PT =
      15.2 (86.0% Activity) (INR = 1.09). Due to the minimal blood loss in the surgical
      field, a new test with citrate was requested to determine the platelet count
      (results: 138,000 platelets). CONCLUSIONS: The anomalous result of an isolated
      exam without corresponding clinical signs should not guide the treatment. All
      exams have a defined percentage of errors and the search for those technical
      errors can avoid the use of the wrong treatment.

PMID- 19382409
TI  - Neuropathic pain--neurochemical aspects.
AB  - BACKGROUND AND OBJECTIVES: Neuropathic pain is caused by damage or inflammation
      of the nervous system. It is a complex syndrome and its biological mechanisms,
      involving inflammatory and immunologic theories, are not clear. The objective of
      this review was to describe the main biologic factors associated with neuropathic
      pain, making a logical association between hypotheses suggested in the
      literature. CONTENTS: The main neuromediators, ion channels, and cells, including
      cells in the nervous system involved in neuronal excitation are described, and
      the possible activation sequence or interaction among those agents in the
      neoplastic change secondary to nerve damage are emphasized. CONCLUSIONS: It was
      possible to conclude that the advances on the knowledge of the pathophysiology of
      neuropathic pain can determine new pharmacologic approaches for this syndrome.

PMID- 19382410
TI  - Myocardial protection by pre- and post-anesthetic conditioning.
AB  - BACKGROUND AND OBJECTIVES: Perioperative myocardial ischemia is commonly
      observed, and it can increase significantly postoperative morbidity and
      mortality. The cardioprotective properties of volatile anesthetics and opioids
      have been studied during several decades and currently constitute powerful tools
      in the management of patients with ischemic coronariopathy. The objective of this
      review was to provide the fundaments of myocardial protection by preconditioning.
      CONTENTS: The concepts of cellular damage secondary to ischemia and reperfusion,
      ischemic preconditioning (IPC), and anesthetic preconditioning (APC), as well as
      the mechanisms of myocardial protection, are discussed. Recent studies in cardiac
      surgery demonstrated that the use of short periods of ischemia during reperfusion
      can reduce the area of myocardial infarction. Volatile anesthetic can also have a
      protective effect in myocardial reperfusion. Independently of the signaling
      pathway that leads to preconditioning, both anesthetic and ischemic,
      mitochondrial dependent KATP channels are considered the final mediators of
      cardioprotection by controlling the mitochondrial influx of calcium and,
      therefore, preventing the induction of necrosis and apoptosis. Although IPC and
      APC effectively reduce the area of myocardial infarction and improve
      postoperative ventricular function, it is important to stress that those
      treatments should be instituted before ischemic events to justify their clinical
      applicability. CONCLUSIONS: Phenomena known as myocardial ischemic
      preconditioning and anesthetic preconditioning are well known, and the mechanism
      of protection is similar in both situations; however, not every step that leads
      to this protection has been fully explained. Further studies are necessary to
      increase the clinical applicability of the cardioprotective properties of
      anesthetics.

PMID- 19382411
TI  - Anesthesia for endovascular surgery of the abdominal aorta.
AB  - BACKGROUND AND OBJECTIVES: Endovascular surgery for aneurism of the aorta is less
      invasive than the conventional procedure besides other advantages such as the
      absence of abdominal incision, absence of ligature of the aorta, and reduced
      postoperative recovery time. Since it is a relatively new procedure and to
      presenting a series of changes that should be known by the anesthesiologist, the
      objective of this report was to review the most relevant aspects of endovascular
      surgery, allowing more adequate perioperative anesthetic management. CONTENTS: A
      brief description of the technique of endovascular aneurism repair, possible
      vantages and disadvantages of its use, as well as potential complications are
      discussed. CONCLUSIONS: Knowledge of the changes secondary to the endovascular
      procedure allows a more adequate anesthetic conduct and improves the
      postoperative results in those patients.

PMID- 19382412
TI  - The role of peripheral opiate antagonists in pain medicine and perioperative
      care.
AB  - BACKGROUND AND OBJECTIVES: Pre-clinical and clinical trials of peripheral opiate
      antagonists have shed new light on the effects of exogenous and endogenous
      opioids. CONTENTS: This article review preclinical studies and clinical opioid
      bowel disfunction trials. CONCLUSIONS: If approved these drugs may offer
      potential solutions to important clinical problems in pain management.

PMID- 19382413
TI  - Continuous infusion of remifentanil versus sufentanil in videolaparoscopic
      surgeries. A comparative study.

PMID- 19382415
TI  - Intraoperative pulmonary barotrauma during ophthalmologic surgery. Case report.

PMID- 19382414
TI  - Comparative study between 0.125% racemic bupivacaine (S50-R50) and 0.125% and
      0.25% of 50% enantiomeric excess bupivacaine in epidural block for labor
      analgesia.

PMID- 19382416
TI  - The nuclear stethoscope in China.

PMID- 19382417
TI  - Recommendations on strengthening the development of nuclear medicine in China.
AB  - This paper outlines briefly the role of nuclear medicine in life sciences and
      health care. Molecular imaging by using isotopic tracers can noninvasively
      visualize the chemistry or hidden process in the cells and tissues inside the
      body, obtaining "functional" images to provide early information of any disease
      and revealing the secrets of life. The vitality of nuclear medicine is its
      ability to translate bench into new clinical application that can benefits the
      patients. Although nuclear medicine community in China has made significant
      achievement with a great effort since 1950s, there are many obstacles to future
      development. Recommended measures are proposed here in an attempt to solve our
      existing problems.

PMID- 19382418
TI  - Pitfalls in positron emission tomography/computed tomography imaging: causes and
      their classifications.
AB  - OBJECTIVE: To describe the pitfalls in positron emission tomography/computed
      tomography (PET/CT) imaging and classify them according to the principles of
      their generation. METHODS: We summarized retrospectively the 18F
      fluorodeoxyglucose (FDP) PET/CT imaging pitfalls through reviewing the PET/CT
      images of 872 patients. The pitfalls were divided into artifacts and infrequent
      physiological uptake, and the artifacts were further classified according to
      their causes. Meanwhile, we calculated the incidences of various pitfalls.
      Whether the PET/CT pitfalls influenced the diagnostic decision was analyzed. The
      appearances of pitfalls in PET were also described. RESULTS: Pitfalls could be
      found in PET/CT images of 684 (78.4%) patients. Artifacts were found in 664
      (76.15%) patients, and could be classified into self-factor artifacts and
      equipment- or technology-related artifacts. Among self-factor artifacts,
      respiratory motion (57.5%), postprandial or hyperglycemia artifacts (2.41%), and
      metal or high density matter artifacts (1.38%) were frequent. As for equipment-
      or technology-related factors, injection point outleakage or radiotracer
      contamination (13.88%) and truncation artifacts (1.83%) were most common ones.
      Infrequent physiological FDG uptakes, including fatty uptake, endometrial uptake,
      and bilateral breast feeding period uptake, were found in 20 (2.29%) patients.
      Among all pitfalls, the artifacts in 92 (13.4%) patients and infrequent
      physiological uptakes in 6 (0.88%) patients affected the diagnostic results.
      Artifact images in PET could be described as hot or cold area and the images of
      infrequent physiological uptake were always shown as hot area. CONCLUSIONS: The
      incidence of pitfall in PET/CT imaging was high and the causes of pitfalls are
      various. Among all causes that artifacts generated, respiratory motion is the
      most common. Some pitfalls may disturb clinical physicians' decision, so it is
      important to recognize artifacts and physiological uptake, and distinguish them
      from pathological uptakes.

PMID- 19382419
TI  - Heteroplasmy level of the mitochondrial tRNaLeu(UUR) A3243G mutation in a Chinese
      family is positively associated with earlier age-of-onset and increasing severity
      of diabetes.
AB  - OBJECTIVE: To investigate the mutations of mitochondrial genome in a pedigree
      with suspected maternally inherited diabetes and deafness and to explore the
      correlations between the mutations and clinical features. METHODS: Genomic DNA
      was isolated from blood leucocytes of each member of the pedigree. The
      mitochondrial genome was amplified with 24-pair primers that could cover the
      entire mitochondrial DNA. Direct sequencing of PCR products was used to identify
      any mitochondrial DNA mutations. RESULTS: Family members on the maternal side all
      harbored the tRNALeu(UUR) A3243G mutation. The paternal side family members did
      not have the mutation. The age-of-onset of diabetes of the 4 maternal side family
      members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy
      level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of
      onset of diabetes and heteroplasmy level of A3243G mutation were negatively
      correlated with a correlation coefficient of -0.980 (P = 0.02). Meanwhile,
      patient with high heteroplasmy level of A3243G mutation had relatively low
      severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were
      found. CONCLUSIONS: The main cause of diabetes in this pedigree is the
      tRNALeu(UUR) A3243G mutation. However, other gene variants may contribute to its
      pathogenicity. The heteroplasmy level of the tRNALeu(UUR) A3243G mutation is
      positively associated with earlier age-of-onset and increasing severity of
      diabetes.

PMID- 19382420
TI  - C-jun N-terminal kinase-mediated signaling is essential for Staphylococcus aureus
      induced U937 apoptosis.
AB  - OBJECTIVE: To investigate the effect of SP600125, a specific c-jun N-terminal
      protein kinase (JNK) inhibitor, on Staphylococcus aureus (S. aureus)-induced U937
      cell death and the underlying mechanism. METHODS: The human monocytic U937 cells
      were treated with S. aureus at different time with or without SP600125. Cell
      apoptosis was analyzed by flow cytometry. JNK, Bax, and caspase-3 activities were
      detected by Western blotting. RESULTS: S. aureus induced apoptosis in cultured
      U937 cells in a time-dependent manner. Expression of Bax and phospho-JNK
      significantly increased in S. aureus-treated U937 cells, and the level of
      activated caspase-3 also increased in a time-dependent manner. Inhibition of JNK
      with SP600125 significantly inhibited S. aureus-induced apoptosis in U937 cells.
      CONCLUSIONS: S. aureus can induce apoptosis in U937 cells by phosphorylation of
      JNK and activation of Bax and caspase-3. SP600125 protects U937 cells from
      apoptosis induced by S. aureus via inhibiting the activity of JNK.

PMID- 19382421
TI  - Posterior selective thoracic fusion in adolescent idiopathic scoliosis patients:
      a comparison of all pedicle screws versus hybrid instrumentation.
AB  - OBJECTIVE: To analyze the influence of segmental pedicle screws versus hybrid
      instrumentation on the correction results in adolescent idiopathic scoliosis
      patients undergoing posterior selective thoracic fusion, METHODS: By reviewing
      the medical records and roentgenograms of adolescent idiopathic scoliosis
      patients who underwent selective thoracic fusion from February 2000 to January
      2007 in our hospital, the patients were divided into 2 groups according to
      different instrumentation fashions: Group A was hook-screw-rod (hybrid) internal
      fixation type, Group B was screw-rod (all pedicle screws) internal fixation type,
      and the screws were used in every segment on the concave side of the thoracic
      curve. The parameters of the scoliosis were measured and the correction results
      were analyzed, RESULTS: Totally, 48 patients (7 males, 41 females) were included,
      with an average age of 14.4 years old and a mean follow-up time of 12.3 months.
      Thirty and 18 patients were assigned to group A and group B, respectively. The
      mean preoperative coronal Cobb angles of the thoracic curve were 48.8 degrees and
      47.4 degrees, respectively. After surgery, they were corrected to 13.7 degrees
      and 6.8 degrees, respectively. At final follow-up, they were 17.0 degrees and 9.5
      degrees, with an average correction rate of 64.6% and 79.0%, respectively, and
      the correction rate of group B was significantly higher than that of group A (P =
      0.003). The mean preoperative coronal Cobb angles of the lumbar curve were 32.6
      degrees and 35.2 degrees, respectively. After surgery, they were corrected to 8.6
      degrees and 8.3 degrees, respectively. At final follow-up, they were 10.3 degrees
      and 11.1 degrees, with an average correction rate of 66.8% and 69.9%,
      respectively, and the correction rate of group B was significantly higher than
      that of group A (P = 0.003). The correction loss of the thoracic curve and lumbar
      curve in the 2 groups were 3.1 degrees and 1.8 degrees, 2.4 degrees and 2.4
      degrees, respectively. No significant difference was noted (both P > 0.05). The
      decompensation rate at final follow-up in these 2 groups were 4% (1/25) and 7.1%
      (1/14) respectively, with no significant difference (P > 0.05). CONCLUSIONS: Both
      all pedicle screws and hybrid instrumentation can offer good correction results
      of the thoracic curve and lumbar curve in posterior selective thoracic fusion in
      patients with adolescent idiopathic scoliosis. While with all pedicle screws, the
      correction results of the thoracic curve and lumbar curve are both better than
      those with hybrid instrumentation without increased decompensation rate.

PMID- 19382422
TI  - Application of computed tomographic colonography in diagnosis of colonic polyps.
AB  - OBJECTIVE: To assess the clinical values of computed tomographic colonography
      (CTC) in diagnosis of colonic polyps. METHODS: Forty-two patients who were
      clinically suspicious of colonic polyps or underwent colonic polyps screening
      received examinations with both CTC and conventional colonoscopy. Sixteen- or 64
      slice spiral computed tomography and professional imaging processing techniques
      were used for evaluation. Per-polyp and per-patient results were analyzed. Those
      by per-polyp were subsequently divided into > or = 10 mm group, 5-10 mm group,
      and < or =5 mm group. Sensitivity, positive predictive value (PPV), specificity,
      negative predictive value (NPV), and accuracy were calculated using statistical
      method for diagnostic studies, with conventional colonoscopy as a gold standard.
      RESULTS: Ninety and 61 polyps were found by CTC and conventional colonoscopy,
      respectively. The per-polyp sensitivity/PPV were 80.3%/55.6% in total, and
      100%/92.9%, 93.8%/65.2%, and 68.8%/ 41.5% in the > or = 10 mm group, 5-10 mm
      group, and < or =5 mm group, respectively. The per-patient sensitivity, PPV,
      specificity, NPV, and accuracy were 97.1%, 89.5%, 42.9%, 75.0%, and 88.1%,
      respectively. CONCLUSION: CTC can clearly reveal the morphology of colonic polyps
      and be used as a routine monitoring method for the clinical diagnosis of polyps.

PMID- 19382423
TI  - Neurogenesis by activation of inherent neural stem cells in the rat hippocampus
      after cerebral infarction.
AB  - OBJECTIVE: To investigate the changes of neural stem cells (NSCs) in the rat
      hippocampus after cerebral infarction (CI) and to evaluate the neurogenesis
      caused by the activation of NSCs. METHODS: CI models of rats were made and rats
      were assigned to 6 groups: sham-operated, 1 day, 3 days, 7 days, 14 days, and 28
      days after CI. The dynamic expression of bromodeoxyuridine (BrdU), polysialylated
      neural cell adhesion molecule (PSA-NCAM), glial fibrillary acidic protein (GFAP),
      and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and
      immunofluorescence staining. BrdU was used to mark the proliferated NSCs. PSA
      NCAM was used to mark the plasticity of activated NSCs. GFAP and NeuN were used
      to mark the differentiated NSCs. RESULTS: Compared with the controls, the number
      of BrdU+ cells in the hippocampus increased significantly at 1 day after CI (P <
      0.05), reached peak at 7 days after CI (P < 0.05), decreased but still elevated
      compared with the controls at 14 days after CI (P < 0.05), and nearly unchanged
      at 28 days after CI. The number of BrdU+/PSA-NCAM+ cells increased significantly
      at 7 days after CI (P < 0.05), reached peak at 14 days after CI (P < 0.05), and
      decreased but still elevated compared with the controls at 28 days after CI (P <
      0.05). The number of BrdU+/PSA-NCAM+ cells was equal to 60% of the number of
      BrdU+ cells in all the same period. The number of BrdU+/NeuN+ cells in the
      hippocampus increased significantly at 14 days after CI (P < 0.05) and reached
      peak at 28 day after CI (P < 0.05). The number of BrdU+/GFAP+ cells in the
      hippocampus nearly unchanged after CI. CONCLUSION: CI can stimulate the
      proliferation of inherent NSCs, and most proliferated NSCs may differentiate into
      neurons and represent neural plasticity.

PMID- 19382424
TI  - Dynamic radiographic analysis of sympathetic cervical spondylosis instability.
AB  - OBJECTIVE: To investigate the correlation between subaxial cervical spine
      instability and cervical spondylotic sympathetic symptoms as well as the
      difference of cervical spondylotic subaxial instability between male and female
      patients. METHODS: We analyzed retrospectively 318 surgical cases of cervical
      spondylosis treated at Department of Orthopedic Surgery of Peking Union Medical
      College Hospital between July 2003 and December 2007. All cases were divided into
      group A without sympathetic symptoms (n=284) and group B with sympathetic
      symptoms (n=34). Angular and horizontal translation values between two adjacent
      vertebral bodies from C2 to C7 were measured separately on hyperflexion and
      hyperextension lateral cervical spine radiographs. Fisher's exact test was used
      to evaluate the correlation between subaxial cervical instability and sympathetic
      symptoms. Intragroup correlation between patient gender and subaxial cervical
      instability was also evaluated. RESULTS: Subaxial instability incidences in
      groups A and B were 21.8% (62/284) and 55.9% (19/34), respectively. Statistical
      analysis indicated a definite correlation between subaxial cervical instability
      and sympathetic symptoms (P=0.000). Among patients without sympathetic symptoms,
      subaxial instability incidences were 21.4% (37/173) in males and 22.5% (25/111)
      in females, respectively (P=0.883). While among patients with sympathetic
      symptoms, subaxial instability incidences were 27.3% (3/11) in males and 69.6%
      (16/23) in females, respectively, indicating significant difference (P=0.030).
      Subaxial instability was most commonly seen at C4-C5 intervertebral space in
      sympathetic cervical spondylosis patients. CONCLUSIONS: High correlation exists
      between subaxial cervical spine instability and cervical spondylotic sympathetic
      symptoms, especially in female patients. Hyperextension and hyperflexion
      radiographs of cervical spine are important to assess sympathetic cervical
      spondylotic subaxial instability.

PMID- 19382425
TI  - Expression of CC chemokine ligand 5 in patients with rheumatoid arthritis and its
      correlation with disease activity and medication.
AB  - OBJECTIVE: To determine the levels of CC chemokine ligand 5 (CCL5) in serum and
      synovial fluid (SF) from patients with rheumatoid arthritis (RA) and their
      relations with disease activity and medication. METHODS: CCL5 in serum and SF was
      quantified by enzyme-linked immunosorbent assay (ELISA) in 28 RA patients and 21
      osteoarthritis (OA) patients. In RA patients, the correlations of CCL5 levels in
      serum and SF with disease activity were analyzed. Meanwhile, the serum CCL5
      levels among RA patients treated with disease-modifying antirheumatic drugs
      (DMARDs), Tripterygium Glucosides, and other Chinese herbs without disease
      modifying effects were also compared. RESULTS: CCL5 levels in both serum and SF
      of RA patients were significantly higher than those of OA patients (P < 0.05).
      Moreover, the level of CCL5 was higher in SF than that in serum of RA patients (P
      < 0.01). Serum CCL5 level was correlated significantly with the number of swollen
      joints (r = 0.3329, P < 0.05), erythrocyte sedimentation rate (r = 0.4001, P <
      0.05), and C reactive protein (r = 0.3735, P < 0.01). In addition, the level of
      CCL5 had a trend of lower in patients treated with DMARDs or Tripterygium
      Glucosides than those treated with other Chinese herbs, although the difference
      was not significant among those patients due to the small number of patients in
      each group. CONCLUSIONS: In RA patients, the expression of CCL5 increases and
      correlates with some clinical and laboratory parameters of RA, which indicate
      that CCL5 plays an important role in RA and may serve as a useful marker of
      disease activity. DMARDs and Tripterygium Glucosides might exert their clinical
      effects through reducing CCL5 production in RA.

PMID- 19382426
TI  - Effects of glutamine supplementation on patients undergoing abdominal surgery.
AB  - OBJECTIVE: To evaluate the effects of supplementation of glutamine (GLN) on
      maintaining glutathione (GSH) level, immune system function, liver function, and
      clinical outcome of patients receiving abdominal operation. METHODS: Forty
      patients undergoing elective abdominal surgical treatment were randomly divided
      into 2 groups: study group (n = 20) and control group (n = 20). All patients
      received total parenteral nutrition (TPN) for up to 7 days during perioperative
      period. The study group received TPN supplemented with GLN dipeptide while the
      control group received TPN without GLN dipeptide. Patients in both groups
      received equivalent nitrogen and caloric intake. Blood sample was taken on
      preoperative day, and the 1st, 3rd, 6th postoperative day to measure GSH level,
      immune indexes, and liver function indexes. RESULTS: The decrease of GSH level in
      plasma and red blood cell (RBC) in study group was less than that in control
      group during postoperative period. Ratio of GSH/glutathione disulfide (GSSG) in
      plasma in study group was higher than that in control group on the 3rd
      postoperative day (52.53 +/- 11.46 vs. 31.43 +/- 7.27, P = 0.001). Albumin level
      in study group was higher than that in control group on the 3rd postoperative day
      (37.7 +/- 3.8 g/L vs. 33.8 +/- 4.2 g/L, P = 0.02). There was no significant
      difference in the levels of immunoglobin (IgG, IgM, IgA) or T lymphocyte subgroup
      (CD4, CD8, CD4/CD8) in both groups during postoperative period. There was one
      case with infectious complication in control group, while none in study group. A
      trend of shortened hospital stay was observed in study group compared with
      control group (22.3 +/- 2.1 d vs. 24.9 +/- 1.7 d, P = 0.32). CONCLUSIONS:
      Supplementation of GLN-enriched TPN has beneficial effects on maintaining GSH
      levels in plasma and RBC, sustaining GSH/GSSG ratio and albumin level, and
      keeping antioxidant abilities during postoperative period in patients with
      abdominal operation, with the trends of decreasing incidence of infectious
      complication and shortening hospital stay.

PMID- 19382427
TI  - Clinical features and treatment of bronchogenic cyst in adults.
AB  - OBJECTIVE: To investigate the clinical features and management of bronchogenic
      cyst in the adults. METHODS: We retrospectively reviewed 50 patients admitted to
      our hospital with histopathologically proved bronchogenic cyst from January 1983
      to December 2007. Of all the patients, 28 were male and 22 were female, with an
      average age of 36.9 (range, 18 to 64) years. The symptoms, location of the cysts,
      imaging evaluation, surgical treatment manner, and outcome of these patients were
      analyzed. RESULTS: Symptoms were present in 33 of the 50 patients, and cough was
      the most common symptom. Thirteen patients presented with complications:
      hemoptysis, infected cyst, dysphagia, paralysis, and hoarseness. The locations of
      the cysts included the mediastinum (28 cases), pulmonary parenchyma (12 cases),
      hilar area (3 cases), visceral pleura (1 case), and some rare locations including
      the intestinal mesentery (1 case), retroperitoneum (1 case), adrenal gland (1
      case), neck (2 cases), and dura matter of the cervical vertebrae (1 case). Chest
      X-ray was performed in 36 patients and computed tomography (CT) was performed in
      41 patients. The bronchogenic cyst in CT was characterized as a round, well
      circumscribed, unilocular mass, with density ranging from that of water to high
      density (0-50 Hu). As for treatment, complete resection of the bronchogenic cyst
      was performed in 47 (94%) patients, subtotal resection was performed in 3 (6%)
      patients. Open surgery was performed in 45 (90%) patients, and thoracoscopy
      (video-assisted thoracic surgery) was performed in 5 (10%) paitients. Of the 12
      patients with intrapulmonary cyst, 11 patients underwent lobectomy and 1 patient
      underwent wedge resection. Postoperative sequelae occurred in 2 patients, 1 with
      persistent air leakage and 1 with hoarseness. All patients were proved with
      bronchogenic cyst pathologically. The average follow-up period was 6.5 years
      (range, 4 months to 10 years), and no late sequelae or recurrence of the cyst
      occurred. CONCLUSIONS: The clinical and imaging presentations of bronchogenic
      cyst in adults are variable. Surgical resection is the best way for diagnosis and
      treatment. Both open surgery and thoracoscopy are appropriate for the selected
      candidates.

PMID- 19382428
TI  - Comparison of three methods of protein extraction from Dermatophagoides
      pteronyssinus for two-dimensional electrophoresis.
AB  - OBJECTIVE: To explore an effective method of Dermatophagoides pteronyssinus
      protein extraction suitable for two-dimensional electrophoresis (2-DE) analysis.
      METHODS: The extracts of Dermatophagoides pteronyssinus were prepared with Coca's
      solution, lysis buffer of 2-DE, and Trizol reagent, respectively. Bicinchoninic
      acid (BCA) assay was used to determine the total protein concentration of the
      samples. The efficiency of different protein extraction methods were evaluated
      with 2-DE analysis. RESULTS: The concentrations of extracted protein by methods
      of Coca's solution, lysis buffer, and Trizol reagent were 0.63 g/L, 0.90 g/L, and
      0.80 g/L, respectively. The 2-DE analysis results showed that some protein spots
      in low molecular weight (LMW) range could be detected with the Coca's solution
      method. With the lysis buffer of 2-DE method, more protein spots in LMW range
      could be detected, while the medium molecular weight (MMW) protein spots were
      absent. Several MMW protein spots (174-178 kD and 133 kD) and more LMW protein
      spots were detected with Trizol reagent method. CONCLUSIONS: Among Coca's
      solution, lysis buffer of 2-DE, and Trizol reagent, the concentration of
      extracted protein of Dermatophagoides pteronyssinus by lysis buffer of 2-DE is
      the highest. However, most protein components of Dermatophagoides pteronyssinus
      purified mite bodies can be extracted by Trizol reagent, which may generally
      reflect the whole profile of Dermatophagoides pteronyssinus allergens.

PMID- 19382429
TI  - [Conflict management in the nursing team].

PMID- 19382430
TI  - [Natural healing in nursing. II: Wraps and compresses].

PMID- 19382431
TI  - [National socialism and nursing in Austria--still (not) a topic? A model workshop
      for the history curriculum].

PMID- 19382432
TI  - [Position of the Professional Pediatric Nursing Society (BeKD) on nursing basic
      supports and nurse counseling of children 20 November 2008].

PMID- 19382433
TI  - [How are clinical guidelines implemented in routine clinical nursing?].

PMID- 19382434
TI  - [Infant counseling in ambulatory pediatric nursing. The SAFE program].

PMID- 19382435
TI  - [Study of skin care in premature and newborn infants].

PMID- 19382436
TI  - [Baby swimming--a pleasure for the body, mind and soul. Seminar for professional
      personnel].

PMID- 19382437
TI  - [Teachers learn... dealing with chronically ill children].

PMID- 19382438
TI  - [Study of means of formulating prescription based on combination disease with
      syndrome].
AB  - The way of combination diseases and syndrome is an important style to diagnose
      and treat disease in traditional Chinese medicine (TCM) clinical practice today.
      The thoughts of formulating prescription based on combination modern diseases and
      syndrome changed profoundly and many styles arose. Combination pathogenesis with
      pathology to formulate prescription compensated for the insufficiency of
      treatment based on symptom differentiation. Combination effects of traditional
      Chinese medicine herbs with pharmacology action reflects a return from
      pharmacologic action to effects of traditional chinese herbs; Fixed prescription
      is sublimation of treatment according to syndrome differentiation. Changing
      classic prescription is still a major mean to formulate prescription. Integrating
      traditional chinese medicinal herbs with western drugs enhanced effect and
      reduced the side effects. Effective extract compatibility is a result and
      develoment of modern research and traditional theory about TCM.

PMID- 19382439
TI  - [Functional genomic approaches to explore secondary metabolites in medicinal
      plants].
AB  - Extensive genomic data concerning medicinal plants are rather scarce and insights
      of the secondary metabolic pathways and their regulatory mechanism are
      insufficient, hampering the broad application of cell or tissue cultivation and
      metabolic engineering to producing high-value secondary metabolites. The
      integration of cDNA-AFLP based transcript profiling and metabolomics, a new
      development of functional genomic approaches could establish correlations between
      the changes of secondary metabolites and expressions of related genes. It has
      manifested widely applicative prospects in seeking genes involved in biosynthesis
      of secondary metabolites and exploring secondary metabolic pathways. Functional
      genomic approaches are promising trends in the field of medicinal plants
      secondary metabolites research and will lead to better utilization of natural
      medicinal resources.

PMID- 19382440
TI  - [Progress on antitumor effects of Marsdenia tenacissima].
AB  - The article reviewed the progress in the research of antitumor activities and
      mechanisms of Marsdenia tenacissima. Its origin producing area and antitumor
      constituents were analyzed. The herb possessed extensive antitumor effects in
      experimental and clinical applications. It provides theoretical evidences for
      study on constituents in this traditional Chinese medicine. Futher studies on the
      species in M. tenacissima are needed for better medicinal utilization.

PMID- 19382441
TI  - [New method of "ingredient difference phonetypical cloning" for functional gene
      cloning from medicinal plants].
AB  - This paper introduced a new method of "ingredient difference phonetypical
      cloning" for functional gene clone of medicinal plants, which might solve the
      difficulties in isolating genes encoding enzymes for the biosynthesis of
      secondary metabolites by usual ways. Concepts, mechanisms and methods were
      systematically introduced and possibility was proved by experiments. The method
      showed the extra superiority of for the isolation of the genes belonged to
      unknown metabolic pathway and little information about its sequences. The method
      provides a new way to isolate functional gene cloning from Chinese herbs and a
      fundament for the further study on medicinal plant genetic engineering.

PMID- 19382442
TI  - [Effects of continuous cropping obstacle on growth of Rehmannia glutinosa].
AB  - OBJECTIVE: To study the effects of continuous cropping obstacles on growth of
      Rehmannia glutinosa. METHOD: The growth indexes, activity of root ATPase, root
      activity and mineral nutritional absorption were determined. RESULT: Continuous
      copping decreased growth rate and declined the size of leaves. Activity of root
      ATPase and root activity were also inhibited. CONCLUSION: The deficiency of
      source capacity is an important factor to restrain the root development of R.
      glutinosa with continuous cropping, the decrease of root activity and ATPase
      activity as well as nutritional stress of potassium and nitrogen are the reasons
      for the effects of continuous cropping on the growth and development of R.
      glutinosa.

PMID- 19382443
TI  - [Dynamic research of density on Platycodon grandiflorum dry material accumulation
      and platycodin D content in Platycodon grandiflorum].
AB  - OBJECTIVE: To study the dynamic changes of dry material accumulation and
      platycodin D content in Platycodon grandiflorum in different planting densities.
      METHOD: Five different planting densities M1 (4 cm x 25 cm), M2 (6 cm x 25 cm),
      M3 (8 cm x 25 cm), M4 (10 cm x 25 cm) and M5 (12 cm x 25 cm) were designed in the
      plot experiment. The individual and colony biomass accumulation, dry material
      distribution, root yield and platycodin D content were measured in different
      stage. RESULT: In a certain density range the individual biomass in P.
      grandiflorum obviously declined with increasing density with the exception of
      biomass M2 > biomass M3. On the contrary, the colony biomass increased with the
      increasing density. Dry material accumulation in each organ in P. grandiflorum in
      different planting densities showed significance (P<0.05). The dry material
      distribution in organs in the different planting densities showed significance
      (P<0.05), and the dry material distribution in flower and fruit reached the
      minimal level in M2, in the same planting density the distribution in root
      reached the maximal; The dry material in stem, flower and fruit obviously
      declined with the increasing density, while the dry material in leaf increased.
      The individual root output increased with the increasing density, and it reached
      the highest in M2. The colony root yield increased with the increasing density.
      The platycodin D content in P. grandiflorum reached the highest in M2.
      CONCLUSION: The result showed that a suitable planting density is very important
      to P. grandiflorum dry material accumulation and distribution, root yield,
      platycodin D content and colony yield.

PMID- 19382444
TI  - [Studies on shapes and germination characters of Alisma plantago-aquatica seeds].
AB  - OBJECTIVE: To explore the differences of the shapes of seeds and germination
      characters of Alisma plantago-aquatica. METHOD: The seeds were collected from
      four regions in Sichuan province, characters of the seeds' appearance were
      observed. The purification, weights per thousand seeds, content of moisture, seed
      vigor and different germination rates of A. plantago-aquatica were measured. The
      germination rates of the seeds were determined under different temperature
      treatments. RESULT: It was markedly varied in shapes of the seeds, rates of
      germination and all quality characters of the four local species. The seeds from
      Pengshan showed the best quality, the weights per thousand, the seed vigor and
      germination rate were 0.4308 g, 6% and 82%, respectively, and the size of the
      seed, its width and length were 1.882, 1.455 mm, respectively. The length was
      positively correlated with the width, and so did the weights per thousand seeds
      with the seed vigor and germination rates. The rate of seed vigor was positively
      correlated with the rate of germination. Results indicated that temperature had
      affected the germination of the seed. CONCLUSION: The seed from Pengshan was the
      best. The result of this study provides scientific evidences for identification,
      growth and cultivation of A. plantago-aquatica.

PMID- 19382445
TI  - [Preparation and release characterization in vitro of pulsed-release tablets of
      compound Danshen].
AB  - OBJECTIVE: To prepare pulsed-release tablet (PTS) according to the rhythm of
      coronary heart disease based on efficacy material and the mechanism of compound
      Danshen. METHOD: PTS were achieved by coating the core which contains drugs, CMS
      Na, lactose, succinic acid and MCC with separation layer (Eudragit RL), swelling
      layer (HPMC E5), and controlled-release membrane (Eudragit RS-RL-EC). RESULT: The
      results of in vitro experiments showed that no difference was observed among the
      profiles of Danshensu, protocatechuic aldehyde, ginsenoside Rg1, Rb1,
      notoginsenoside R1 release from the two-step release system. And it indicated
      that swelling was the basis and prerequisite for drug release from PTS, and the
      diffusion, organic acid-induced, and osmotic pumping mechanism were involved in
      drug release, but the latter they were the dominant factors. CONCLUSION:
      Successfully obtained the PTS of a certain lag-time behind the rapid release
      which indicate that after bed time administration of such device, the drug plasma
      concentration-time curve CAN meet the requirements of chronotherapy of
      cardiovascular disease.

PMID- 19382446
TI  - [Influence of different technique process and prescription on dampproof
      performance of pharmaceutical materials of traditional Chinese medicine].
AB  - OBJECTIVE: To study the influence of different technique process and prescription
      on hygroscopic property of pharmaceutical materials of traditional Chinese
      medecine (TCM) was studied. METHOD: The sample prepared with banlangen and
      different excipients had been put in certain suroundings for 24 hours, then the
      hygroscopic curves and their parameters of hydroscopicity were gotten; the
      influence of that on hygscopic property of banlangen was studied. RESULT: The
      optimized damp-proof materials was polyoxylate II. The damp-proof effect enhanced
      with the increase of temperature and the excipient the decrease of and
      concentration of ethanol. CONCLUSION: Excipients have different effect on
      hyproscopic property of banlangen, and the damp-proof technology has direct
      effect on it.

PMID- 19382447
TI  - [Study on preparation and quantity determination of Scrophularia ningpoensis
      dispensing granules].
AB  - OBJECTIVE: To develop the preparation method and to determine the quantity of
      effective constituents of Scrophularia ningpoensis dispensing granules. METHOD:
      Nine experiments were carried out through L9 (3(4)) orthogonal design. The
      contents of harpagoside and cinnamic acid were determined by HPLC method. RESULT:
      The optimal extraction process was as follows: the slices were soaked in water in
      the ratio of 1:8 for 0.5 h, then they were decocted for 2 h. For the second time,
      6 times of water was added and sustained for 1.5 h. Harpagoside and cinnamic acid
      were linear within the ranges of 0.0776-1.552 microg (r=0.9999) and 0.01446
      0.4339 microg (r=0.9999), respectively. The average recoveries were 100.4% (RSD
      1.98%, n=6) and 98.27% (RSD1.35%, n=6), respectively. Ten batches of granules
      were determined. CONCLUSION: The extraction process is scientific and the
      determination method is suitable for quality control of Scrophularia ningpoensis
      dispensing granules.

PMID- 19382448
TI  - [Studies on self-microemulsifying drug preparations of total flavones of
      Hippophae rhamnoides].
AB  - OBJECTIVE: To develop self-microemulsifying preparations of total flavones of
      Hippophae Rhamnoides L. (TFH) and the determination method of dissolution.
      METHOD: The equilibrium solubility of TFH in different compositions of oils,
      emulsifier and assistant emulsifier was investigated. The self-microemulsion
      formula was optimized by constructing the pseudo-ternary phase diagrams of blank
      SMEDDS determining the self-microemulsifying efficiency and the stability of the
      SMEDDS. The 2 hours dissolution curve of TFH self-microemulsifying preparations
      was established. The optimal self-microemulsion formula was composed of MIGLYOL
      812 N, Cremophor EL and 1,2-Propylene glycol. RESULT: The ratio of them was
      0.5:5.7:3.8. The average particle size was 12.1 nm. The dissolution rate at 10
      minutes of TFH self-microemulsifying preparation was 131% higher than that of
      Xinda kang tablets. CONCLUSION: The acquired microemulsion with small particle
      size is stable. The dissolution rate is evidently improved compared with market
      dosage forms.

PMID- 19382449
TI  - [Study on stability of oridonin solution].
AB  - OBJECTIVE: To investigate the stability of oridonin (ORI) solution for research
      and development of novel ORI prepartions. METHOD: The effect of pH on the
      degradation rate of ORI was evaluated, the pH values of the oridonin solutions
      were adjusted to the setting pH, with 1 mol x L(-1) HCl or NaOH, respectively,
      and stored at room temperature for 60 h. The constant temperature method was
      applied to evaluate the stability of ORI solution at room temperature and at 4
      degrees C. RESULT: The pH-rate profile of ORI was V-shaped, and the pHm was 5.
      The t90 of ORI solution at room temperature was 53.2 h and 91.5 h at 4 degrees C
      CONCLUSION: The ORI solution is not stable. The pH-dependent degradation of ORI
      solution confirms to specific acid-base catalysis reaction.

PMID- 19382450
TI  - [Germplasm resources of Polygala tenuifolia and determination of presenegenin in
      processing products].
AB  - OBJECTIVE: To research the germplasm resources and the contents of senegenin in
      processing products of Polygala tenuifolia. METHOD: The contents of senegenin in
      wild Polygala tenuifolia and cultivated samples of Polygala tenuifolia were
      determined by RP-HPLC, and compared. RESULT: The contents of senegenin in wild
      reduce gradually along Shaanxi, Shanxi, Hebei to Dongbei. The contents of
      senegenin in cultivated three-year samples of three year Polygala tenuifolia from
      five main place was similar, 0.44%-0.49%. The content of senegenin were 0.44%
      0.64% in the wand and 0.03%-0.09% in the residual part of stem, and the content
      of senegenin in Polygala tenuifolia was more than that in processing products.
      CONCLUSION: There is a correlation between the content of senegenin in Polygala
      tenuifolia and ecology environment that show a is inverse proportion with the
      quality grade, and the contents in the processing products were decreased.
      Senegenin can be used as a characteristic marker in range. This research provides
      a reference for search a index for quality control of Radix polygala and its
      processing products.

PMID- 19382451
TI  - [Studies on chemical constituents of roasted seeds of Cassia obtusifolia].
AB  - OBJECTIVE: To investigate the chemical constituents of the roasted seeds of
      Cassia obtusifolia to illuminate the change of its effective components before
      and after roasted. METHOD: Compounds were separated by silica gel chromatography,
      and their structures were evaluated by spectral analysis and chemical evidence.
      RESULT: Seven compounds were isolated from the ethanol extract. Their structures
      were identified as chrysophanol (1), physcion (2), 8-methoxylchrysophanol (3),
      beta-sitosterol (4), emodin (5), obtusin (6) and obtusifolin-2-O-beta-D-(6'-O
      acetyl) glucopyranside (7). CONCLUSION: Compounds 1-7 were isolated from the
      roasted seeds of C. obtusifolia for the first time, and compound 7 was a new
      compound.

PMID- 19382452
TI  - [Two iridoid glycoside from roots of Phlomis medicinalis].
AB  - OBJECTIVE: To study the chemical constituents of the roots of Phlomis
      medicinalis. METHOD: The compounds were isolated and repeatedly purified by
      macroporous resin, silica gel column chromatography, TLC and PREP-HPLC. Their
      structures were elucidated by physical and chemical properties and NMR spectra.
      RESULT: Two iridoid glucosides were obtained and elucidated as 7-epilamalbide
      (1), chlorotuberoside (2). CONCLUSION: Compound 1 was a new compound, compound 2
      was isolated from the plant for the first time.

PMID- 19382453
TI  - [Bioactive sterols from red alga Acanthophora spicifera boergesen].
AB  - OBJECTIVE: To study the chemical constituents of the red alga Acanthophora
      spicifera boergesen aiming at searching for bioactive leading compounds. METHOD:
      Compounds were isolated by various chromatographic techniques including column
      chromatography over normal phase silica gel and Sephadex LH-20 gel and reverse
      phase HPLC as well as recrystallization. Their structures were determined by
      spectroscopic methods including IR, MS, 1D and 2D NMR techniques. MTT method was
      used for testing cytotoxicity of compounds against human cancer cell lines HCT-8,
      Bel-7402, BGC-823, A549 and HELA. Their inhibition against proliferation of dog
      vascular smooth muscle cells was also screened by MTT assay. RESULT: Six sterols
      were isolated from the ethanolic extract of the red alga Acanthophora spicifera.
      Their structures were identified as 6-hydroxycholest-4-ene-3-one (1), cholest-4
      ene-3, 6-dione (2), cholest-5-ene-3 beta-ol (3), 5 alpha-cholestane-3, 6-dione
      (4), beta-sitosterol (5) and saringosterol (6). CONCLUSION: Compounds 1-3 and 5
      were obtained from this genus for the first time. Compounds 1, 2 and 4 showed
      moderate cytotoxic activity against human cancer cell lines.

PMID- 19382454
TI  - [Study on chemical diversity of volatile oils in Houttuynia cordata and their
      genetic basis].
AB  - OBJECTIVE: To reveal chemical diversify of volatile oils in Houttuynia cordata
      from major producing areas in China and their genetic basis, lay a foundation for
      breeding a quality H. cordata variety. METHOD: The volatile oils in H. cordata
      from 22 provenances were determined by GC. And the relationship among the peak
      areas of volatile oils, biological characteristics and RAPD makers were analyzed.
      RESULT: There were common and special volatile oils in H. cordata from different
      provenances. The peak areas of common volatile oils in samples were significantly
      different. The clustering figure based on the peak areas or the relative peak
      areas of common volatile oils was almost agreed with the one based on RAPD makers
      analysis. And the differences in chromatograms could be distinguished according
      to the biological characteristics. CONCLUSION: The diversity of volatile oils
      exists in H. cordata from different provenances which relate with biological
      characteristics and has genetic basis. H. cordata can be divided into 2 types
      according to volatile oils, biological characteristics or RAPD marker.

PMID- 19382455
TI  - [Determination of five compounds in Scrophularia ningpoensis by HPLC-UV-ELSD].
AB  - OBJECTIVE: To develop an HPLC-UV-ELSD method for the determination of aucubi,
      harpagide, harpagoside, angoroside C and cinnamic acid in Scrophularia
      ningpoensis. METHOD: The analytical column was SHIMADZU C18 (4.6 mm x 250 mm, 5
      microm). The mobile phase was acetonirile-0.4% acetic acid in a gradient elution.
      Initial conditions was 5% A; 0-20 min, changed to 10% A; 20-50 min, to 55% A. The
      flow rate was 0.8 mL x min(-1) and the column temperature was 30 degrees C. The
      UV detector wavelength was set at 280 nm for harpagoside, angoroside C and
      cinnamic acid, and the evaporative light-scattering detector (ELSD) drift tube
      temperature was 105 degrees C, the flow rate of nebulizer gas was 1.2 L x min(-1)
      for aucubi and harpagide. RESULT: Aucubi, harpagide, harpagoside, angoroside C
      and cinnamic acid was separated well. The linear calibration curves were obtained
      over of 0.752-13.536 microg for aucubi (r=0.9993, n=6), 0.8280-14.90 microg for
      harpagide (r=0.9994, n=6), 0.6360-11.45 microg for harpagoside (r=0.9997, n=6),
      0.5440- 9.792 microg for angoroside C, (r=0.9997, n=6) and 0.0108-0.1939 microg
      for cinnamic acid (r=0.9999, n=6). The mean recovers of five compounds were
      98.12%, 99.14%, 100.21%, 98.17% and 100.35% with RSD of 2.3%, 1.5%, 1.9%, 1.7%
      and 0.5%. CONCLUSION: This method could simultaneously determinate the content of
      the five compounds in the S. ningpoensis.

PMID- 19382456
TI  - [Suppressive effects of GTW treatment on infiltration of inflammatory cell in
      glomeruli in anti-Thy1.1 glomerulonephritis].
AB  - OBJECTIVE: To examine inhibition action of multi-glycoside of Tripterygium
      wilfordii (GTW) on infiltration of inflammatory cell in glomeruli with anti
      Thy1.1 glomerulonephritis (anti-Thy1.1 GN), and to clarify its effects on
      inflammatory in vitro. METHOD: Two types of anti-Thy1.1 GN were induced in rats
      by a single or two intravenous injections with 500 microg of anti-Thy1.1 mAb 1-22
      3. Rats were randomly divided into two groups, the GTW group and control group,
      and sacrificed on day 7 or on day 42 after induction of anti-Thy1.1 GN. Daily
      oral administration of different dose of GTW and distilled water as a control was
      started from 3 days before injection or at the same time of injection till the
      day of sacrifice. Proteinuria was determined during days 7 or during days 42.
      Infiltration of macrophage and T lymphocyte in glomeruli and mRNA expression of
      interleukin (IL)-2 and interferon (IFN)-gamma in renal tissue were examined.
      RESULT: Increase of infiltration of macrophage in reversible anti-Thy1.1 GN
      model, glomerular macrophage infiltration and IL-2 mRNA expansion were attenuated
      by higher dose of GTW (75 mg x kg(-1) x d(-1)), and increased accumulation of
      activated macrophage and T lymphocyte in irreversible anti-Thy1.1 GN model,
      accumulation of macrophage and T lymphocyte in glomeruli and mRNA expansion of IL
      2 and IFN-gamma were decreased by middling dose of GTW (50 mg x kg(-1) x d(-1))
      as well. Proteinuria was significantly ameliorated after GTW administration.
      CONCLUSION: The findings suggested that different dose of GTW can ameliorate
      infiltration of inflammatory cell in glomeruli with anti-Thy1.1
      glomerulonephritis in vitro by decreasing the expression of IL-2 and IFN-gamma.

PMID- 19382457
TI  - [Effect of dauricine on apoptosis and expression of apoptogenic protein after
      transient focal cerebral ischemia-reperfusion injury in rats].
AB  - OBJECTIVE: To investigate the effect of dauricine on the apoptosis of neuronal
      cells and the expression of apoptosis-related proteins in the brain penumbra of
      rats induced by transient focal cerebral ischemia-reperfusion injury. METHOD:
      Male SD rats were randomly divided into five groups: sham group (Sham), model
      group (Model), and Dauricine groups of low, middle and high doses. To make the
      transient focal cerebral ischemia-reperfusion injury model, the middle cerebral
      artery on the right side of rat was occluded by inserting a nylon suture through
      the internal carotid artery for 1 h, followed by reperfusion for 24 h after
      withdrawing the suture. Dauricine groups, different doses of Dauricine (2.5, 5,
      10 mg x kg(-1) as low, middle and high dose respectively) were administered
      intraperitoneally at the beginning of the cerebral ischemia, and at 11 h and 23 h
      after reperfusion. At the same time, Sham group and Model group was administered
      saline as controls. Brain samples of rats were treated with paraformaldehyde
      perfusion fixation 24 h after blood reperfusion and then collected for making
      pathological sections. Apoptotic changes of neuronal cells in the brain penumbra
      of rat were evaluated in situ by terminal deoxyribonucleotidyl
      transferasemediated dUTP-digoxigenin nick end-labelling (TUNEL). Cytochrome C
      (Cyt-C) release and the expression of caspase -3 and caspase -9 proteins of the
      ischemic-reperfusion brain tissue were determined by immunohistochemistry assay.
      RESULT: TUNEL-positive cells in groups of middle and high doses of dauricine
      (18.9 +/- 2.02 and 15.9 +/- 2.9 cells/mm2 respectively) decreased significantly
      compared with model group (25.5 +/- 3.3 cells/mm2, P<0.05). Cyt-C release and the
      expression of caspase-3 and caspase-9 proteins in groups of middle and high doses
      of dauricine were also inhibited compared with Model group (P<0.01). CONCLUSION:
      The mechanism of the neuroprotective effect of dauricine after cerebral ischemia
      reperfusion injury may parly, related with an inhibition of neuronal cells
      apoptosis in the penumbra.

PMID- 19382458
TI  - [Effect of tetramethylpyrazine on expression of Smad7 and SnoN in rats with UUO].
AB  - OBJECTIVE: To study effect and mechanisms of tetramethylpyrazine (TMP) on renal
      interstitial fibrosis induced by unilateral ureteral obstruction in rats. METHOD:
      Eighteen male Sprague-Dawley rats were randomly divided into sham-operated group,
      model group and TMP group, 6 in each group. The model of renal interstitial
      fibrosisi was established in rats by unilateral ureteral obstruction. All rats
      were killed at the end of the 3rd week after treatment. Pathological change and
      collagen deposition of the kidneys in rats were observed with HE staining and
      Masson's collagen staining, respectively. The contents of procollagen III N
      terminal peptide and TGF-beta 1 in renal tissue homogenates were tested by
      radioimmunoassay and ELISA, respective. Protein expression levels of Smad 7 and
      the Smad transcriptional corepressors SnoN in the obstructed kidney were analyzed
      by Western blotting. RESULT: Pathological examination of the kidneys in the model
      group showed renal tubule atrophied and lumens expanded, tubular interstitium
      broadened, large amount of collagen interstitial deposited. The contents of
      procollagen III N-terminal peptide and TGF-beta 1 were higher and the protein
      expression levels of Smad7 and SnoN were significantly lower than those in the
      sham-operated group. Compared with the model group, TMP ameliorated the
      pathological lesion of the obstructed kidney, decreased the procollagen III N
      terminal peptide and TGF-beta 1 contents, significantly increased the expression
      levels of Smad7 and SnoN protein. CONCLUSION: TMP can evidently resist renal
      interstitial fibrosis induced by UUO in rats, which might be related with down
      regulation of the contents of TGF-beta 1, which is a potent profibrosis cytokine,
      meanwhile up-regulation of the protein expression levels of Smad7 and SnoN in
      renal tissue.

PMID- 19382459
TI  - [Effects of Erbie San on Walker-256 liver cancer and adjustment to unbalance of
      VEGF/endostatin in rats].
AB  - OBJECTIVE: To investigate the anticancer effects of Erbie San on the rats bearing
      Walker-256 liver cancer and the potential mechanism of its angiogenesis effects.
      METHOD: Wistar rats bearing Walker-256 liver cancer were used in this study. The
      experimental groups were treated with Erbie San 1.25, 2.5, 5 g x kg(-1) x d(-1),
      and 5-Fluorouracil injection 75 mg x kg(-1), respectively. The tumor's weight,
      the expression of VEGF, Endostatin and the ratio of VEGF/endostatin in serum of
      each groups were observed. RESULT: Compared to the model group, Erbie San 2.5, 5
      g x kg(-1) x d (-1) and 5-Fluorouracil injection groups can reduce the tumor's
      weight significantly (P<0.05 or P<0.01). The expression of VEGF was reduced,
      while endostatin was increased, and the ratio of VEGF/endostatin was reduced
      (P<0.05 or P<0.01). CONCLUSION: Erbie San can effectively inhibit the growth of
      Walker-256 liver cancer of rats and can inhibit the expression of VEGF but
      increase the expression of endostatin, which suggest that Erbie San has the
      inhibition of angiogenesis which is responsible for its anticancer effects.

PMID- 19382460
TI  - [Study of molecular mechanism of Rheum offcinale against Yersinia pestis].
AB  - To investigate molecular mechanism of traditional Chinese medicine Rheum
      offcinale against Yersinia pestis, whole genome DNA microarray that contains 4005
      annotated genes of Y. pestis was used. The minimal inhibition concentration (MIC)
      of R. offcinale extract against Y. pestis was determined by liquid dilution
      method. The gene expression profile of Y. pestis was performed after exposured to
      R. offcinale extract at a concentration of 10 X MIC for 30 and 60 minutes. The
      total RNA extracted and purified from Y. pestis were reverse-transcribed to cDNA
      and labeled by Cy3-Cy5 dye. The labeled probes were hybridized to the microarray
      and the results were obtained by a laser scanner and analyzed by the SAM
      software. The microarray data was confirmed by RT-PCR. The platform of the DNA
      microarray-based bacteria transcriptional profiling was eshtablished. The results
      revealed general gene expression changes of Y. pestis were a global phenomenon.
      Down-regulation of genes encoding proteins involved in ribosome protein synthesis
      was a remarkable change. Genes encoding cell envelope and transport/binding
      proteins were the major changed genes of the Y. pestis in response to R.
      offcinale.

PMID- 19382461
TI  - [Protective effect of hawthorn leaf procyanidins on cardiomyocytes of neonatal
      rats subjected to simulated ischemia-reperfusion injury].
AB  - OBJECTIVE: To study the direct effect of hawthorn leaf procyanidins on
      cardiomyocytes subjected to ischemia-reperfusion injury and elucidate their
      therapeutic mechanism on ischemic heart diseases. METHOD: Cultured cardiomyocytes
      of neonatal rats were subjected to anoxia-reoxia injury which simulated the
      ischemia-reperfusion injury in vivo, and hawthorn leaf procyanidins were applied.
      The therapeutic effect was valued by LDH leakage and MTT test. For a further
      mechanism study, contents of MDA and activities of SOD in cardiomyocytes were
      measured. RESULT: Hawthorn leaf procyanidins in 24-60 mg x L(-1) significantly
      and dose-dependently inhibited LDH leakage (compared with the model group, all
      P<0.01 ) and cell viability decrease (compared with model group, 24-48 mg x L(-1)
      groups all P<0.05; 60 mg x L(-1) group, P<0.01) in cardiomyocytes induced by
      anoxia-reoxia injury. Furthermore, hawthorn leaf procyanidins in 24-60 mg x L(-1)
      significantly inhibited the increase of MDA content (compared with the model
      group, all P<0.01) and the decreased of SOD activity (compared with the model
      group, 24 mg x L(-1) group, P<0.05; other groups all P<0.01) in cardiomyocytes
      undergoing anoxia-reoxia injury. CONCLUSION: Hawthorn leaf procyanidins have a
      significant therapeutic effect on the simulated ischemia-reperfusion injury of
      cultured neonatal rat cardiomyocytes, which may relate to their anti-oxidation
      effects. And the direct protective effect of hawthorn leaf procyanidins on
      cardiomyocytes subjected to ischemia-reperfusion injury may be one of the key
      mechanisms of its therapeutic effect on ischemic heart diseases.

PMID- 19382462
TI  - [Effects of Sarcandra glabra extract on immune activity in restraint stress
      mice].
AB  - OBJECTIVE: To study the protective effect of Sarcandra glabra extract (SGE) on
      immune system in restrained mice. METHOD: The male C57BL/6 mice were randomly
      divided into normal control group, stress control group, 125, 500 mg x kg(-1) SGE
      group. The spleen lymphocyte suspensions of each group were prepared. The
      parameters of spleen T cells subsets, NK cell and NKT cell proportion and number
      was detected by Flow cytometry. RESULT: SGE regulated the balance of T cell
      subsets, increased the percent of NK cells and NKT cell proportion and number in
      restrained mice. CONCLUSION: SGE has immunologic protective effect in restrained
      mice probably via the amelioration of immune cells proportion and number.

PMID- 19382463
TI  - [Study of clinical effect on treatment of chronic obstructive pulmonary disease
      in acute aggravated stage with Tanreqing injection and cell factor level].
AB  - OBJECTIVE: To make a study of the clinical effect on the treatment of chronic
      obstructive pulmonary disease in acute aggravated stage with Tanreqing Injection
      and the changes of the cell factor level. METHOD: Eighty-seven cases of COPD
      patients in acute aggravated stage were chosen and divided into two groups at
      random. Forty-four cases in treatment group were given intravenous drip of
      Tanreqing (20 mL) with 5% G/NS (500 mL) once a day. Forty-three cases in control
      group were given intravenous drip Yanhuning injection (0.4 g) with 5% G/NS (500
      mL) once a day. The courses of the treatment were both two weeks and the changes
      of TL-10, TNF-alpha and MPO were observed separately before and after the
      treatment. RESULT: The total effective rate in the treatment group was 94.31%
      while the control group 83.75%, which had significant difference (P<0.05). IL-10
      level in both groups was comparatively lower than the healthy (P<0.01), while TNF
      alpha and MPO was higher than the healthy (P<0.01). After the treatment, the TNF
      alpha and MPO level in the treatment group decreased more greatly than those in
      the control groups (P<0.01) but the IL-10 increased a lot more than those in the
      control group and there existed remarkable difference (P<0.01). CONCLUSION: The
      treatment of chronic obstructive pulmonary disease in acute aggravated stage with
      Tanreqing Injection can have noticeable effect, and can prohibit the release of
      above cell factors. It is also safe in clinical use without obvious side effects
      and has played an important role in the treatment of chronic obstructive
      pulmonary disease in acute aggravated stage.

PMID- 19382464
TI  - [Existing problems in researches on the application of Tripterygium].

PMID- 19382465
TI  - [Discussion and suggestions on some problems of the research and application of
      Tripterygium in China].

PMID- 19382466
TI  - [Difficulties and countermeasures in treatment of rheumatoid arthritis with
      Tripterygium].

PMID- 19382467
TI  - [Preliminary study on predictors for selection of immunosuppressive therapy or
      androgens in treating aplastic anemia patients].
AB  - OBJECTIVE: To evaluate the potential usefulness of a multivariable model,
      established mainly upon peripheral T-cell subsets, Th1/Th2, T-bet and GATA-3 gene
      expressions as well as TCM and Western medical diagnostic criteria, in predicting
      the selection of immunosuppressive therapy (IST) or androgens in treating
      patients with aplastic anemia (AA). METHODS: Peripheral blood T cell subsets in
      85 patients with AA were serially analyzed by flow cytometry before and after
      treatment, and their T-bet and GATA-3 gene expressions were assessed meantime by
      Real-time PCR. Then analysis of Logistic regression equation and ROC curves were
      performed based on the cases responding to IST or androgens. RESULTS: (1)
      According to the logistic equation and ROC curve of SPSS, setting the false
      positive rate as 0.10, the P value was 0.832. When P> or =0.832, patients were
      judged in the immunosuppressive dominant state, IST should be applied; when
      P<0.832, it means patients in the bone marrow failure dominant state, androgens
      should be added. (2) A novel theory is raised by the above-mentioned analysis,
      which indicated that the genesis and development process of AA could be divided
      in 2 stages, the abnormal immune dominant stage and the bone marrow failure
      dominant stage. For treatment of patients in the two stages, IST and androgens is
      the preference respectively. CONCLUSION: The multivariable model could be used
      for indicating which stage the AA patient is in, the abnormal immune stage or the
      bone marrow failure stage, and thus to guide the proper selection of IST or
      androgens in clinical practice.

PMID- 19382468
TI  - [The significance of combined therapy of arsenic trioxide and all-trans retinoic
      acid in treating acute promyelocytic leukemia].
AB  - OBJECTIVE: To explore the significance of combined therapy of arsenic trioxide
      (As2O3) and all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL).
      METHODS: Retrospective study of 80 APL patients was performed and the complete
      remission (CR), the recovery time of peripheral hemoglobin and platelet, the
      early mortality, and the adverse reaction rates were analyzed between the ATRA
      group and the ATRA combined As2O3 group (combined group). RESULTS: CR rate of the
      combined group and the ATRA group was 91.7% and 87.5% respectively, which showed
      no significant difference; time of reaching CR, hemoglobin recovery, and platelet
      recovery for the combined group were 28.0 +/- 7.8 days, 22.36 +/- 8.72 days and
      19.38 +/- 9.52 days respectively, while those were 47.7 +/- 10.9 days, 28.40 +/-
      8.95 days and 28.03 +/- 7.29 days for the ATRA group, which suggested a
      significantly shorter period of the combined group of achieving recovery. With
      7.1% compared to 13.2%, the early mortality of the combined group seemed lower
      than that of the ATRA group but with no significance observed (P>0.05). The
      adverse reaction rates of the two groups also lacked any significant difference
      (P>0.05). CONCLUSION: Compared with using ATRA alone, the combined therapy of
      AS2O3 and ATRA was dominant in achieving CR and recovery for APL. Besides, the
      combined therapy carries the promise of reducing the early mortality with no
      aggravation of the adverse reaction.

PMID- 19382469
TI  - [Effect of an integrative medical regimen on levels of vascular endothelial
      function and hypersensitive C-reactive protein in elderly patients with isolated
      systolic hypertension].
AB  - OBJECTIVE: To observe the effect of a integrative medical regimen (IMR), i.e.
      combined use of Jiangya Capsule (JYC) and Nimodipine (ND), on blood pressure, TCM
      clinical symptoms, and blood levels of vascular endothelial function and
      hypersensitive C-reactive protein (hs-CRP) in elderly patients with isolated
      systolic hypertension (EISH). METHODS: Adopting randomized, double-blinded and
      controlled principle, a trial was conducted on 135 patients with EISH by
      randomized them into three groups, they were administered IMR (Group A), JYC plus
      ND simulator (Group B) and ND plus JYC simulator (Group C) respectively, for 4
      weeks. Changes of blood pressure and TCM symptoms, as well as the levels of serum
      nitric oxide (NO), plasma endothelin-1 (ET-1), 6-keto-prostaglandin 1alpha (6
      keto-PGF(1alpha)), thromboxane B2 (TXB2) and hs-CRP were observed before and
      after treatment. RESULTS: After treatment the systolic blood pressure reduced and
      clinical symptoms improved, with serum NO and 6-keto-PGF(1alpha) lelels elevated,
      plasma ET-1, TXB2 and serum hs-CRP decreased in all the three groups (P<0.05 or
      P<0.01). But the inter-group comparisons showed that the effect in Group A was
      superior to the other two groups in decreasing systolic pressure, and superior to
      Group C in improving clinical symptoms, elevating serum NO and decreasing plasma
      TXB2 (P <0.05). CONCLUSION: The integrative medical regimen of combined use JYC
      and ND has markedly effect in lowering blood pressure, it could obviously improve
      the symptoms and vascular endothelial function, and inhibit the level of
      inflammatory factor in patients with EISH.

PMID- 19382470
TI  - [Relationship between immune imbalance and sthenia-asthenia syndromes in patients
      suffering from severe intra-abdominal infection].
AB  - OBJECTIVE: To explore the characteristics of immune imbalance in patients with
      multiple organ dysfunction syndrome (MODS) induced by severe intra-abdominal
      infection and its relationship with changing of TCM sthenia-asthenia syndrome.
      METHODS: Forty-six patients with MODS induced by severe intra-abdominal infection
      and treated with etiological and syndrome differentiation of integrative medicine
      were observed in succession. Patients' peripheral blood levels of interleukin
      6/interleukin-10 ratio (IL-6/IL-10), human leukocyte antigen DR site (HLA-DR),
      helper T lymphocyte1/2 ratio (Th1/Th2), and the regulatory T lymphocyte (Treg)
      were measured on the 1st, 3rd and 7th day of the research respectively. And the
      distribution laws of TCM syndrome types, sthenia (S), asthenia (A), and mingled
      sthenia/asthenia (M), in patients were observed as well. RESULTS: IL-6/IL-10
      ratio at all the testing time points showed insignificant difference in patients
      of types S and M, while in those of type A, it was more lowered on the 7th day
      than that on the 1st day. HLA-DR lowered to <30% on the 7th day in all patients
      of type A and showed significant difference to that on the 1st day (P <0.05),
      while HLA-DR <30% was not found in all patients of types S and M. Th1/Th2 ratio
      in patients of types S and A was insignificant different at the foremost 3 days,
      but lowered significantly on the 7th day, while in patients of type M, it was
      unchanged in all the 7 days of observation. Treg level was unchanged in the
      foremost 3 days in patients of types S and M, while in those of type A, it raised
      on the 3rd day, but no raising was found in the subsequent 4 days. Comparisons of
      various indexes detected at corresponding time points respectively among patients
      with various syndrome types showed that, for levels of IL-6/IL-8, HLA-DR, and
      Th1/Th2, the sequence was S>M>A; and for Treg, it was A>M>S. CONCLUSION: In the
      pathological process of MODS induced by severe intra-abdominal infection, the
      index IL-6/IL-10, reflecting the balance of the pro-/anti-inflammatory cytokines
      and the indexes HLA-DR, Th1/Th2 and Treg reflecting the immune function, all can
      exactly reflect the TCM asthenia-sthenia syndrome types. The sequence in patients
      of various syndrome types for levels of IL-6/IL-10, HLA-DR and Th1/Th2, is S>
      M>A, but for Treg it is the inverse, as A>M>S.

PMID- 19382471
TI  - [Treatment of severe acute biliary pancreatitis in the elderly by integrated
      traditional Chinese and Western medicine].
AB  - OBJECTIVE: To summarize the therapeutic effect of integrated traditional Chinese
      and Western medicine (ICWM) on severe acute biliary pancreatitis (SABP), and to
      discuss the opportunity of operation. METHODS: The hospitalization duration,
      incidence of complications, operation transmitting rate and mortality were
      analyzed in 96 senile SABP patients (Group A) treated by ICWM, and 32 senile SABP
      patients treated by conventional Western medicine, they were hospitalized from
      January 2000 to December 2007. RESULTS: (1) The average hospitalization duration
      in Group A and B was 28.2 +/- 11.3 days and 32.7 +/- 14.3 days respectively,
      showing insignificant difference between them (P>0.05); (2) The early stage
      incidence of complications being 29.2% (28/96) in Group A and 34.4% (11/32) in
      Group B, no significant difference between groups was shown, but a significant
      difference did show at the late stage, 36.5% (35/96) vs 53.1% (17/32), the
      incidence in Group A was lower significantly (P<0.05). (3) The two groups were
      not different in operation transmitting rate 36.4% (35/96) vs 43.8% (14/32),
      P>0.05. (4) The mortality in Group A, 21.9% (21/96) was lower than that in Group
      B, 37.5% (12/32), P <0.05. CONCLUSION: ICWM has good effect in treating SABP, and
      the opportunity of operation transmitting should be decided according to whether
      there obstruction of biliary tract exists or not.

PMID- 19382472
TI  - [Therapeutic effect of early applying hydrotherapy with Chinese drugs on children
      hypoxic ischemic encephalopathy].
AB  - OBJECTIVE: To observe the therapeutic effect of hydrotherapy with Chinese drugs
      (HT-C) in early intervention on children hypoxic ischemic encephalopathy (HIE).
      METHODS: HIE children were assigned to the treatment group and the control group,
      50 in each, at random depending on the willingness of patients' parents. Both
      groups received the conventional functional training, according to the "0 -3-year
      old early intervention outline", but for the treatment group, HT-C was applied
      additionally. Indexes for quality of sleep, gross motor function, severity of
      spasm and intellectual development were observed and compared before and after
      treatment to assess the therapeutic effects. RESULTS: Therapeutic effect in the
      treatment group was better than that in the control group in all the indexes
      observed, showing statistical significance (all P <0.05). CONCLUSION: Early
      intervention of HT-C could improve clinical symptom, promote the functional
      recovery and intellectual development in children HIE, and also could reduce or
      prevent the sequelae occurrence of the nervous system in them.

PMID- 19382473
TI  - [Effect of tanshinone II A on the calcineurin activity in proliferating vascular
      smooth muscle cells of rats].
AB  - OBJECTIVE: To study the effect of tanshinone II A (TSN) on angiotensin II (Ang
      II) induced proliferation of vascular smooth muscle cells (VSMCs). METHODS: VSMCs
      were cultured by explant attached method, and induced to proliferative cell model
      with Ang II. The effect of TSN in different concentrations on calcineurin (CaN)
      activity was detected by enzyme reaction phosphorus measurement; the CaN mRNA
      expression was detected by RT-PCR; and the expression of proliferating cell
      nuclear antigen (PCNA) were observed by immunocytochemical method. RESULTS:
      Compared with the normal control group, Ang II could significantly stimulate the
      proliferation of VSMCs, showing obviously elevated degree of proliferation
      activity (P <0. 01). After being treated with TSN, all the indexes, including CaN
      activity, CaN mRNA expression and PCNA expression, were obviously reduced in a
      dose-dependent manner (P<0.05, P<0.01). CONCLUSION: VSMCs proliferation can be
      inhibited by TSN in a dose-dependent manner and the inhibiting mechanism may be
      related to the down-regulation of CaN activities and the inhibition on CaN mRNA
      and PCNA expressions.

PMID- 19382474
TI  - [Effects of jingtian tongmai recipe on atherosclerotic plaque in rabbits].
AB  - OBJECTIVE: To evaluate the inhibiting effects of Jingtian Tongmai Recipe (JTTMR)
      in different dosages on atherosclerotic plaque using the arteriosclerosis rabbit
      model induced by high cholesterol diet supplemented with immunological injury.
      METHODS: Fifty-four healthy New Zealand rabbits were randomly divided into six
      groups: the normal control group, the model group, the Xuezhikang (XZK) treated
      group and the three JTTMR treated groups treated respectively with low (1.29
      g/kg/day), medium (2.57 g/kg/day) and high (5.14 g/kg/day) dosage of JTTMR.
      Indexes including serum lipids, C-reactive protein (CRP), and area ratio of
      aortic plaque/intima (PIR), and intima-media thickness ratio (IMT) were examined.
      RESULTS: Comparison of blood lipids showed that serum levels of total cholesterol
      (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were
      higher significantly in the model group than in the normal group (P<0.05); TC and
      LDL-C were lower in the XZK group and the JTTMR groups than in the model group
      (P<0.05); and these indexes were significantly lower in the medium dose JTTMR
      group than those in the low and high dose JTTMR groups (P<0.05); while no
      significant difference of TG between the model group, the JTTMR groups and the
      XZK group were observed (P>0.05). As for level of high-density lipoprotein
      cholesterol (HDL-C), that in the XZK group and high dose JTTMR group was higher
      than that in the other 4 groups (P<0.05). Comparison of CRP showed that it was
      higher in the model group than in the normal group (P<0.05), while the difference
      among the other 4 groups was insignificant (P>0.05). No plaque and increase of
      intima/media thickness was found in the normal group; either PIR or IMT were
      lesser in the JTTMR groups than those in the model group (P<0.05), and comparison
      among the three JTTMR groups showed those in the medium dose group was the least
      (P<0.05). CONCLUSION: JTTMR has arteriosclerosis inhibiting effect, which might
      be realized through its anti-inflammatory and lipids regulating actions, but the
      effects are not dose-dependent. The optimal effect is showed by using medium dose
      of JTTMR, equivalent to the dose used for human adult.

PMID- 19382475
TI  - [Rhubarb induced change of tumor necrosis factor-alpha level in guinea pig model
      of melanosis coli and its significance].
AB  - OBJECTIVE: To study the induced change of tumor necrosis factor alpha (TNF-alpha)
      level in serum and colon tissue of guinea pig model with melanosis coli and its
      significance induced by rhubarb (RB). METHODS: One hundred and twelve guinea pigs
      of clean grade were randomly divided into four groups: the 16 in the normal group
      (untreated) and the 3 RB groups (32 in each) treated with low (3 g/kg d), medium
      (6 g/kg d), and high (12 g/kg d) dose of rhubarb respectively, administered by
      gastrogavage for 60 successive days. All guinea pigs were sacrificed at the
      terminal of the experiment and their blood serum and colon tissue were taken for
      detecting TNF-alpha level and TNF-alpha mRNA expression qualitatively and
      quantitatively using ELISA and RT-PCR. RESULTS: Compared with the normal group,
      serum and colonic tissue levels of TNF-alpha and TNF-alpha mRNA expression in the
      RB groups were higher significantly (P<0.01), while no significant difference was
      found among the later three groups (P>0.05). CONCLUSION: RB could induce change
      of TNF-alpha level in serum and colon tissue of guinea pig with melanosis coli.

PMID- 19382476
TI  - [Effects of xiaoyan lidan pian extract on mice with stressive liver injury].
AB  - OBJECTIVE: To investigate the protective effects of Xiaoyan Lidan Pian extract
      (XLP) on restraint stress induced liver injury in mice. METHODS: Liver injury
      mouse model was established by restraint stress. Sixty mice were equally divided
      into 6 groups, the normal control group, the model group, the Thiopronin group,
      and the three XLP groups treated with low (125 mg/kg), moderate (250 mg/kg) and
      high dose (500 mg/kg) XLP respectively. Effect of various treatments was
      evaluated by assessing alanine aminotransferase (ALT) in plasma; malondialdehyde
      (MDA) content in liver by thiobarbituric acid method; content of nitric oxide
      (NO) by Griess chemical method; hepatic antioxidant capacity index (ORAC) by
      fluorescent enzyme immunoassay; glutathione (GSH) content by HPLC; activity of
      glutathione peroxidase (GPX-Px) and glutathione S-transferase (GST) by
      colorimetry; activity of hepatic mitochondrial respiratory chain complex enzyme
      (MRCCE) by ultraviolet spectrophotometry; and contents of cytochrome a, b, c, and
      c1 by the redox differential spectra. RESULTS: As compared with the model group,
      in the XLP groups, level of plasma ALT activity, liver content of MDA and NO, and
      contents of cytochromes were lower, while levels of ORAC index, GSH, GPX-Px and
      GST in liver, and MRCCE activity were higher. CONCLUSION: XLP has definite
      protective effects on stressive liver injury in mice, which may be related to its
      action in alleviating the oxidative stress condition in mice.

PMID- 19382478
TI  - [Effect of allyl glycoside extracted from Herba Rhodiolae on activity and
      proliferation of cultured Schwann cells under high glucose condition].
AB  - OBJECTIVE: To observe changes in activity and proliferation of cultured Schwann
      cells under the high glucose condition and effect of allyl glycoside extracted
      from Herba Rhodiolae (AG) on these changes for exploring the possible mechanism
      of diabetic peripheral nerve injury and the pharmacologic action of AG on them.
      METHODS: Adopting refined Brokes method, Schwann cells were isolated from the
      sciatic nerve tissue of newborn Wistar rats and purified. Their activity and
      proliferative capability were determined using XTT method and 3H-TdR
      incorporative method respectively. RESULTS: High glucose showed marked inhibitory
      effect on both activity and proliferative capability of Schwann cells, and the
      inhibition could be markedly improved by AG. CONCLUSION: Diabetic peripheral
      nerve injury is possibly related to inhibitory effect of high glucose on activity
      and proliferative capability of Schwann cells. Effect of AG in improving these
      inhibitory changes provides the experiment basis for clinical use of traditional
      Chinese medicine, Herba Rhodiolae.

PMID- 19382477
TI  - [Selective effect of nispex in inhibiting human cancer cell proliferation and
      inducing cell apoptosis].
AB  - OBJECTIVE: To observe the in vitro anticancer effect of Nispex, the total
      flavonoids extract from Scurrula parasitic L. METHODS: The cell proliferation
      inhibitory effects of Nispex on various kinds of tumor cells or non-tumor cells
      in human and rats were detected with MTT assay and colony forming assay
      respectively, the cell apoptosis induced by Nispex was detected by AO/EB
      fluorescence staining, TUNEL assay and AnnexinV-FITC/PI flow cytometry. RESULTS:
      Nispex could significantly inhibit human cancer cell proliferation and induce
      human cancer cell apoptosis, especially to the proliferative cell group, but its
      inhibition on human non-tumor cell was insignificant, and showed no effect on
      murine cancer cells in the tested scope. CONCLUSION: Nispex is a nature plant
      extract which shows good selectivity for killing human cancer cell.

PMID- 19382479
TI  - [Effects of lianhuang decoction in treating fetomaternal ABO blood group
      incompatibility].
AB  - OBJECTIVE: To investigate the clinical curative effect of Lianhuang Decoction
      (LHD) in treating fetomaternal ABO blood group incompatibility (FM-ABOI).
      METHODS: Sixty pregnancy women diagnosed as FM-ABOI were randomly assigned to two
      groups, Group A treated with LHD and Group B treated with Western medicine. The
      therapeutic efficacy in the two groups was observed. RESULTS: The antibody titer
      decreased after treatment in both groups to different extent; the effective rate
      was 90.0% in Group A and 56.7% in Group B. The bilirubin level in cord blood of
      Group A was lower than that in Group B significantly (P<0.01). No statistically
      significant difference was found between the two groups new-bom in terms of 5
      minute Apgar score, body weight and hemoglobin content in cord blood (P>0.05).
      CONCLUSION: LHD has good clinical curative effect in treating FM-ABOI, could
      decrease the serum antibody titer, and prevent the occurrence of postpartum
      hemolytic disease in newborns.

PMID- 19382480
TI  - [Effect of tongbian navel paste on colonic motility in children with constipation
      of slow transmission type].
AB  - OBJECTIVE: To observe the therapeutic effect of Tongbian Navel Paste (TBP, a self
      formulated preparation consisting of both Chinese herbal and Western medicines)
      on children with constipation of slow transmission type (CSTT) and it influence
      on patients' colonic motility. METHODS: Sixty-eight children with CSTT were
      randomly assigned to two groups, 38 in the treatment group treated with TBP, and
      30 in the control group treated with oral taking Maren Zipi pill. The changes of
      clinical symptoms, and the outcomes of colon transmission test were observed and
      compared before and after treatment. RESULTS: Colon transmission test showed the
      48 h and 72 h barium discharging rate (%) in the treatment group before treatment
      was 10.1 +/- 3.2 and 46.2 +/- 3.9; after treatment, it raised to 59.9 +/- 4.1 and
      73.6 +/- 3.6 respectively (P <0.05). The total effective rate in the treatment
      group was 89.47% and 73.33% in the control group, the difference between groups
      was significant (P<0.05). CONCLUSION: TBP could promote the motility of colon, it
      is a safe, convenient and effective preparation for treatment of CSTT.

PMID- 19382481
TI  - [Comparison of pragmatic clinical trials and explanatory clinical trials].
AB  - Clinical trials are often designed as either pragmatic or explanatory. The
      pragmatic clinical trials are generally used for measuring the effectiveness of a
      treatment in common clinical practice, while the explanatory trial for measuring
      the efficacy of a treatment under ideal conditions. Since the methods concerning
      pragmatic clinical trials are less introduced in China, its archetypal features,
      advantages and limitations were introduced in this paper. And a current study of
      pragmatic clinical trials on using acpuncture for treatment of low back pain
      carried out in German was taken as an example to illustrate the practical methods
      concretely. The key steps of the design were presented in detail, and reasonable
      suggestions about the problems often encountered in the trial, as well as how to
      balance the internal and external validity, outcome measurement, etc., were
      offered.

PMID- 19382482
TI  - [Pathological study on autopsy died of Tripterygium intoxication--report of 4
      cases].
AB  - The Tripterygium preparation, a Chinese herbal medicine, has been widely used to
      treat various autoimmune diseases, such as rheumatoid arthritis and systemic
      lupus erythematosus. Its significant clinical effects have received a great
      praise and attention by the public health in China, but its toxicity also
      definitely exists, with the therapeutic dosage approaching the minimal toxic
      dosage. In order to provide reference for the safe use of Tripterygium
      preparation in clinical practice, the pathological changes of 4 autopsy cases by
      Tripterygium poisoning were reported in this paper. In them, 2 cases died of
      acute cardiogenic shock caused by myocardial damage, showing hydropic
      degeneration of the myocardial cells, even with obvious contraction band necrosis
      in the papillary muscles; the other 2 died of severe acute renal failure due to
      severe acute toxic nephrosis; cerebral edema and gastrointestinal inflammatory
      changes were found in all cases. The authors suggested that careful dosage
      control is the key step to prevent Tripterygium intoxication during the medical
      treatments; directly using the crude Tripterygium in clinics should be
      prohibited; and the Tripterygium preparation used should be produced by the
      pharmaceutical companies regulated by the government.

PMID- 19382483
TI  - [Probe in the untranslatability of technical terms in traditional Chinese
      medicine].
AB  - Based on studying the manifestation of untranslatability of traditional Chinese
      medicine (TCM) technical terms, and through analysis on the enriched cultural
      content and special linguistic characteristics, the author summarized the factors
      that caused the untranslatability, and suggested some projects for compensation
      and reformation, including transliteration, word-formation, free translation and
      literal translation. Although the existence of untranslatability of TCM technical
      terms is affirmable, on account of the uninterrupted international cultural
      communications, the untranslatability of TCM terms will not be lasting
      invariable.

PMID- 19382484
TI  - [The investigation and progress of the cellular and molecular biological
      mechanisms of Tripterygium wilfordii in treating rheumatoid arthritis].

PMID- 19382485
TI  - [Study on nitric oxide in diabetic peripheral neuropathy and traditional Chinese
      medicine intervention in it].

PMID- 19382486
TI  - Outcomes in rhinology.

PMID- 19382487
TI  - Olfactory bulb volume in the clinical assessment of olfactory dysfunction.
AB  - The olfactory bulb collects the sensory afferents of the olfactory receptor cells
      located in the olfactory neuroepithelium. The olfactory bulb ends with the
      olfactory tract and is closely related to the olfactory sulcus of the frontal
      lobe. Many studies demonstrated that olfactory bulb volume assessed with magnetic
      resonance imaging is related to the olfactory function both in normal and
      pathological conditions. It has been shown that olfactory bulb volume changes
      with the degree of olfactory dysfunction, that it decreases with the duration of
      the olfactory loss and that patients with qualitative disorder such as parosmia
      have smaller olfactory bulbs than patients without parosmia. In this review, we
      will discuss the actual knowledge regarding olfactory bulb function, practical
      ways to measure olfactory bulb volume and olfactory sulcus depth, and report
      systematic observations regarding these measurements related to various causes of
      olfactory dysfunction, e.g. infection of the upper respiratory tract, head
      trauma, or neurodegenerative disease. Measurement of olfactory bulb volume may
      provide valuable information for patients with olfactory dysfunction.

PMID- 19382488
TI  - Patient reported outcome measures in rhinology.
AB  - Patient rated outcome measures (PROMs) are increasingly being used to supplement
      clinical measures of disease in order to assess how disease and medical
      intervention impacts on quality of life. As the primary aim of treatment for most
      rhinological conditions is to improve quality of life they have particular
      relevance in our sub-specialty. Some PROMs have been developed for particular
      conditions or treatments (disease-specific measures) while others were developed
      to be used in all patient groups or healthy individuals (generic measures). There
      are an increasing number of both disease-specific and global measures available
      for use in rhinological conditions, and they are reviewed. Both factors limiting
      wide scale adoption of PROMs into routine practice, and limitations of PROMs are
      also discussed.

PMID- 19382489
TI  - Surgical or medical management of subperiosteal orbital abscess in children: a
      critical appraisal of the literature.
AB  - OBJECTIVE: Subperiosteal orbital abscesses (SPOA) are a complication of
      sinusitis. Traditional treatment of SPOA is surgical. Recently, a number of
      studies report successful medical treatment. To our knowledge, it is unclear
      which patients can benefit from medical management alone. Therefore, we
      questioned (1) what is the outcome of medical versus surgical treatment? (2)
      which patients can be cured with antibiotics alone? (3) what are the absolute
      criteria for surgical treatment? METHODS: A structured search was conducted in
      PubMed, EMBASE and the Cochrane Library for relevant papers which were critically
      appraised. RESULTS: Five studies addressing our clinical questions were included,
      one prospective case series and four retrospective studies. Evidence levels
      varied from 2b to 3. Overall, a high cure rate was achieved with combined
      modality treatment (95.3-100%). The cure rate of medical treatment alone varied
      between 26% and 93%. The outcome of medical treatment improved after prior
      selection of surgical cases. In general, responders to medical treatment had a
      medial abscess associated with ethmoid sinusitis. Criteria for initial surgical
      or medical management differed among authors. Most authors agreed upon initial
      surgical treatment for patients with non-medial abscesses, decreased visual
      acuity and signs of systemic involvement. Surgery was also indicated when lack of
      improvement or worsening of symptoms and signs after 48-72 hours of medical
      treatment were observed. CONCLUSIONS: The outcome of surgical versus medical
      management of SPOA within and between studies could not be compared. Higher cure
      rates were observed when both modalities were combined. There is some evidence
      that medical treatment can cure medially located SPOA. Loss of visual acuity, non
      medial abscess, clinical detoriation and failure to improve within 48 hours of
      antibiotic treatment can be considered as criteria for surgical treatment. In the
      absence of these criteria a trial of antibiotic treatment can be considered with
      close monitoring of the patient.

PMID- 19382490
TI  - What happens to patients with nasal stuffiness and pathological rhinomanometry
      left without surgery?
AB  - In this study we explored long term outcomes of patients with nasal stuffiness
      and high nasal airway resistance (NAR) that did not undergo nasal surgery. The
      same investigation was repeated on average 8 years after a baseline investigation
      with an ENT-examination, a rhinomanometric survey and a rhinomanometry. We did
      follow-up investigations in 44 out of 59 non-operated patients with a
      pathological NAR on at least one side. At follow-up 2 persons (4%) had no
      complaints, 14 (32%) had reduced, 22 (50%) unchanged, and 6 (14%) increased
      complaints of nasal stuffiness. Rhinomanometry showed that NAR values decreased
      significantly between baseline and follow-up on both wider and narrower sides
      after decongestion. There was no correlation between subjective nasal complaints
      and NAR-values. In logistic regression models increasing age and allergy
      prevalence at baseline were significantly associated with having no, or reduced
      nasal stuffiness at follow-up. The results show that both NAR and subjective
      nasal stuffiness decreased with age. Consequently, we suggest that NAR normal
      values should be age adjusted. Also, a wait and see policy towards nasal
      stuffiness seems relevant since 36% of our patients had no or reduced nasal
      stuffiness while their NAR-values were reduced after 8 years.

PMID- 19382491
TI  - Usefulness and feasibility of psychophysical and electrophysiological olfactory
      testing in the rhinology clinic.
AB  - TOPIC: Olfactory dysfunction may be assessed in the clinic with psychophysical
      testing and electrophysiological recording. Chemosensory event-related potentials
      (CSERPs) constitute an objective method to assess chemosensory function.
      Olfactory and trigeminal stimuli activate chemoreceptors from the olfactory
      neuroepithelium and from the nasal mucosa to evoke an electrophysiological
      response respectively called olfactory (OERPs) and trigeminal ERPs (TERPs). The
      purpose of this study is to assess the usefulness and feasibility of these
      diagnostic tools in the rhinology clinic and to correlate these results to the
      olfactory disorder aetiology. MATERIALS AND METHODS: This study encompasses a
      cohort of 229 patients with a complaint of olfactory dysfunction from different
      origins. Orthonasal (Sniffing stick test with the treshold-discrimination
      identification score: maximal score 48) and retronasal olfactory (maximal score
      20) testing as well as CSERPs both after olfactory and trigeminal stimuli have
      been routinely performed. Olfactory dysfunction aetiologies were as follows:
      congenital (Cong.), chronic rhinosinusitis (CRS), idiopathic (Idiop.), post
      medication (PM), neurologic (Neuro.), post-traumatic (PT) and post-infection
      (PI). RESULTS: Mean orthonasal and retronasal scores were respectively: 11.8 and
      10.1 for Cong., 18.5 and 13.1 for CRS, 15.6 and 10.4 for Idiop., 15.3 and 10.2
      for PM, 17 and 10.6 for Neuro., 15 and 9.9 for PT and 18.3 and 12 for PI.
      Correlations between orthonasal and retronasal scores were present for all
      subgroups except congenital and chronic rhinosinusitis subgroups. Orthonasal and
      retronasal scores were different (p < 0.05) when comparing CRS vs Cong., CRS vs
      PT and PT vs PI. Technical problems (olfactometer or olfactory stimulation, EEG
      amplifier,...) and patients discomfort (anxiety, stress,...) did not allow to
      draw any conclusion in 2 patients. Three patients after olfactory stimulus and 6
      patients after trigeminal stimulus demonstrated too much eye blinking or muscular
      artifacts that did not allow us to perform electrophysiological analysis and
      averaging as 60% of artifact-free recording was not achieved. Olfactory ERPs were
      recorded in 28% of the patients and trigeminal ERPs were obtained in almost every
      patient (95%). There was no statistical difference between each subgroup
      regarding the presence or absence of OERPs. CONCLUSIONS: Psychophysical olfactory
      testing is a useful method to assess olfactory function in patients with
      olfactory loss and may help us to obtain a semi-objective and a basal evaluation
      of the olfactory performances. Feasibility and usefulness of CSERPs are also
      underlined in this study with only a limited number of patients who did not
      complete the examination. Psychophysical testing gives different results
      according to the aetiology of the olfactory disorder, which was not the case for
      electrophysiological recording. Olfactory acuity assessment should be based on
      psychophysical and CSERPs evaluation in a clinical setting.

PMID- 19382492
TI  - CMC packing in functional endoscopic sinus surgery: does it affect patient
      comfort?
AB  - BACKGROUND: Functional endoscopic sinus surgery (FESS) has become the treatment
      of choice for patients with medically resistant chronic rhinosinusitis (CRS and
      nasal polyposis). Nasal packing is usually placed after the surgery to minimize
      mucosal bleeding and support the wound healing process. Both the packing itself
      and its removal are often associated with pain and discomfort. OBJECTIVE: To
      evaluate the effect of carboxymethylcellulose (CMC) nasal packing on patient
      comfort following FESS. METHODS: Forty consecutive patients underwent bilateral
      FESS. One side of the nasal cavity was packed with CMC (mesh or gel) and the
      opposite side was not packed, the sides having been randomly selected.
      Postoperatively, patients were given visual analog scales to rate nasal airway
      obstruction and headache/pressure separately for the right and left sides. They
      also rated sleep disturbance and general well-being. RESULTS: No significant
      differences were found between the CMC-packed side and the unpacked side with
      regard to patient comfort. No significant differences were found between CMC mesh
      and CMC gel. CONCLUSION: Based on the presented data concerning patient comfort,
      CMC appears to be an ideal packing material following FESS. However, there is no
      other study revealing an identical study design focusing on other resorbable
      packing material. As a consequence, other available resorbable packing material
      should be investigated to find the ideal packing material following FESS, if
      packing is required.

PMID- 19382493
TI  - A randomised controlled trial comparing Rapid Rhino Mannheim and Netcell series
      5000 packs following routine nasal surgery.
AB  - OBJECTIVES: To determine whether there is a difference in discomfort between
      Netcell Series 5000 and Rapid Rhino Mannheim 8.0 cm (Cat. No. 800) packs used
      after routine nasal surgery, whilst in situ and during removal. This was tested
      in a single blind, randomised controlled trial at the ENT Department, Royal Devon
      & Exeter Hospital. PARTICIPANTS: Adults aged 16-65 undergoing nasal septal
      surgery and trimming of inferior turbinates. Patients were excluded if they were
      undergoing revision surgery, taking anticoagulants, or had a history of sino
      nasal disease or trauma. Thirty nine entered and 32 completed the study. The
      intervention was a different nasal pack in each side of the nose, removed the
      morning after surgery. MAIN OUTCOMES MEASURES: Pain experienced by patients while
      packs are in situ and on removal as recorded on a standard unmarked 100 mm visual
      analogue scale. RESULTS: There was no difference in the pain scores whilst in
      situ. Rapid Rhino Mannheim was more painful on removal (difference = 10.6 mm, p <
      0.001, Wilcoxon signed ranks test). CONCLUSIONS: Rapid Rhino Mannheim packs do
      not confer a benefit over Netcell Series 5000 packs after routine nasal surgery.

PMID- 19382494
TI  - Prevention of ultrasonic coagulator-mediated mucoperiosteal flap injury and
      defects by using a clip manipulation in the resection of the posterior nasal
      nerve.
AB  - We previously reported on the clinical effectiveness of functional inferior
      turbinosurgery utilizing modified vidian neurectomy, the resection of the
      posterior nasal nerve (PNN), combined with inferior turbinoplasty. In order to
      prevent re-innervation of the PNN after resection and to avoid postoperative
      massive hemorrhage--presumably resulting from insufficient fixation and
      unexpected exposure of the bony or cartilaginous fragments covered on the
      resected neurovascular bundle containing the sphenopalatine vessels and the PNN-
      we designed a surgical technique during which a vascular clip was used in order
      to provide traction of the mucoperiosteal flap. Then we compared it with the
      previous procedure (without the use of the clip). The injury and defects of the
      mucoperiosteal flap were evaluated by the degree of exposure to the bony or
      cartilaginous fragments and scored on a scale of 0 to 2 points. The defects of
      the mucoperiosteal flap were reduced by using a vascular clip. The average score
      of the defects was 0.97 +/- 0.73 (n = 64) in the conventional procedure without
      any manipulation and 0.27 +/- 0.45 (n = 60) in the procedure using a vascular
      clip. The difference observed between the two gropups was statistically
      significant (p < 0.001). These results demonstrated that this is a safe technique
      to prevent injury and defects of the mucoperiosteal flap in gaining access to
      expose the PNN. This should promote early wound healing, reduce the chance of
      recurrence and of postoperative massive hemorrhage.

PMID- 19382495
TI  - The impact of endonasal dacryocystorhinostomy (DCR), on patient health status as
      assessed by the Glasgow benefit inventory.
AB  - OBJECTIVE: To measure the effect of Endonasal DCR on the health status of
      patients, using a validated outcomes measure, the Glasgow Benefit Inventory.
      METHOD: Postal questionnaire with telephone follow up of patients undergoing
      Endonasal DCR in two institutions in Scotland. The same surgical technique is
      used in both centres. Patients were identified from prospectively collected data
      on consecutive patients undergoing this procedure. All adult patients, a minimum
      of twelve months post-intervention, were included. RESULTS: Ninety two of 123
      patients (75%) completed the questionnaire, the mean age was 59 years and the sex
      ratio m:f was 1:1.8. The mean overall GBI for this intervention was + 32.7 (95%
      confidence intervals 27.8 - 37.6). The patients were grouped according to the
      indication for intervention: Obstruction of lacrimal system GBI + 32.7 (26.3
      37.1), mucoecele + 40.1 (28.7-51.4), dacryocystitis + 19.4 (10.0-28.9).
      CONCLUSION: The GBI provides a measure of the effect of an ORL intervention on
      the health of a patient. Endonasal DCR scores highly when compared with a number
      of other rhinological procedures including rhinoplasty (GBI + 20), endoscopic
      sinus surgery (GBI + 23), and septal surgery (mean ranges from + 6 to + 24).
      Endonasal DCR is a successful intervention with demonstrable health benefits to
      the patient.

PMID- 19382496
TI  - Treatment of acute rhinosinusitis with the preparation from Pelargonium sidoides
      EPs 7630: a randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the herbal drug preparation
      from the roots of Pelargonium sidoides (EPs 7630) compared to placebo. DESIGN:
      Double-blind, randomized, placebo-controlled, parallel-group, multicenter trial
      with a group-sequential adaptive design. SUBJECTS: Patients with sinonasal
      symptoms of at least 7 days duration, and radiographically and clinically
      confirmed acute rhinosinusitis of presumably bacterial origin with a Sinusitis
      Severity Score (SSS) of at least 12 out of 24 points at inclusion. INTERVENTIONS:
      EPs 7630, a herbal drug preparation from the roots of Pelargonium sidoides (1: 8
      10; extraction solvent: ethanol 11% (w/w)), or matching placebo at a dose of 60
      drops three times daily for maximum 22 days. MAIN OUTCOME MEASURES: Change in the
      SSS after 7 days. RESULTS: 103 patients were recruited until the planned interim
      analysis. The mean decrease in the SSS was 5.5 points in the EPs 7630 group
      compared to 2.5 points in the placebo group, a difference of 3.0 points (95%
      confidence interval 2.0 to 3.9, p < 0.00001). This result was confirmed by all
      secondary parameters indicating a more favourable course of the disease and a
      faster recovery in the EPs 7630 group. According to the pre-specified decision
      rule, the study was stopped after obtaining proof of efficacy for EPs 7630.
      CONCLUSIONS: EPs 7630 was well tolerated and superior in efficacy compared to
      placebo in the treatment of acute rhinosinusitis of presumably bacterial origin.

PMID- 19382497
TI  - Intracranial complications of rhinosinusitis. A review, typical imaging data and
      algorithm of management.
AB  - STATEMENT OF THE PROBLEM: Intracranial complications of acute bacterial sinusitis
      remain life-threatening. We aimed to study the current features of the condition-
      illustration, clinical presentations, risk factors, and define a management
      strategy. METHOD OF STUDY: A retrospective study. Review of inpatients treated
      for meningoencephalitic infections related to sinusitis in a tertiary emergency
      care center between 1992 and 2005. Data retrieved on age, sex, signs at
      admission, bacterial findings, sinus involvement, intracranial complications and
      outcome. We analyzed the relation of bacterial infection to sinus involvement,
      initial signs of intracranial complications, and risk factors, and reviewed the
      literature to define a management strategy. MAIN RESULTS: We retrieved 25 files.
      Intracranial complications related to sinusitis involved largely men between
      second and third decade. No risk factor was clearly identified. Frontal and
      sphenoid sinuses were the most common site involved. Diffuse headache or two-step
      evolution headache and altered mental status were strongly correlated with
      meningitis and brain abscess. Empyema was the most common complication. A
      management algorithm has been defined: computed tomography was early performed to
      diagnose intracranial collection, and was repeated after 48 h if the clinical
      course was not favorable. The sinus was always drained by the safest way.
      Sequelae occurred in 16% of patients. No death occurred with this treatment
      strategy. PRINCIPAL CONCLUSION: Intracranial complications of acute sinusitis are
      exceptional but remain potentially severe and may lead to death. Early imaging
      data and aggressive management, associating sinus and brain drainage, as well as
      combined antibiotic therapy, can limit mortality and the incidence of sequelae.

PMID- 19382498
TI  - A study of poor responders for long-term, low-dose macrolide administration for
      chronic sinusitis.
AB  - PURPOSE: We investigated the clinical factors (CT images, endoscopic nasal
      findings and allergic factors) involved in resistance of chronic sinusitis to
      macrolide therapy (ME) retrospectively. METHODS: ME was administered for 8-20
      weeks in 68 adults with chronic sinusitis cases. The effect was evaluated in each
      factor from radiographic findings (R0-R3 according to the severity of the
      images), nasal findings (N0: no polyp, N1: a single polyp and N2: multiple
      polyps), allergic factors (A0: no allergy, A1: nasal allergy, A2: bronchial
      asthma) and objective nasal symptoms. In addition, an effect after polypectomy
      and histological examination were assessed for N1 and N2 groups. RESULTS: ME was
      effective in 70.6% (48/68 patients). The efficacy of ME was significantly less in
      the polyp group compared with the polyp-free group (p < 0.05). Therapeutic
      efficacy was significantly different between R1 and R3 groups (p < 0.05) with a
      tendency for worse outcome from R1 to R3. The efficacy in asthma patients was
      significantly less compared with patients with allergic rhinitis or no allergy (p
      < 0.05). The efficacy after polypectomy was significantly improved in N2 group
      but not in N1 group. The number of eosinophil/total inflammatory cells (%) in
      nasal polyps of resistant cases was significantly higher than in marked improved
      cases. CONCLUSION: The efficacy of ME was less in patients with polyposis; CT
      scans indicating severe findings, bronchial asthma and polyps with increased
      eosinophil infiltrations. Polypectomy resulted in significant improvement in the
      efficacy of ME.

PMID- 19382499
TI  - A prospective audit to look at the number of plain sinus x-rays requested via the
      radiology department.
AB  - Chronic rhinosinusitis is currently diagnosed on history-taking with
      nasendoscopic confirmation. Sinus x-rays are insensitive and non-specific but are
      still requested, particularly by primary care physicians. The rate of sinus x
      rays can be reduced by informing GPs of current best practice guidelines.

PMID- 19382500
TI  - Rhinosinusitis, symptomatology & absence of polyposis in children with primary
      ciliary dyskinesia.
AB  - INTRODUCTION: Primary Ciliary Dyskinesia (PCD) describes a group of inherited
      disorders which result in functional ciliary defects leading to mucous stasis.
      Clinical manifestations include otitis media with effusion and chronic
      rhinosinusitis. Nasal polyposis has previously been thought to be linked to PCD,
      and current theories of 'polypogenesis' suggest that early and severe polyp
      formation could be expected among sufferers of this condition. METHODS: Cross
      sectional observational review of all children attending the multi-disciplinary
      clinic at a national tertiary-referral centre for PCD across a 3-month period.
      Careful examination was undertaken, and the SNOT-20 questionnaire administered.
      RESULTS: Thirty patients were included. No nasal polyps were found, despite
      children clearly suffering rhinosinusitis and being debilitated by their
      symptoms. The rhinologically orientated questions of the SNOT-20 produced the
      most positive responses; however some other questions were found not to be useful
      in a paediatric population. CONCLUSIONS: Nasal polyps do not occur in children
      with PCD, despite the presence of rhinosinusitis. Given that many current
      theories of polyp pathogenesis hinge on prolongation of proinflammatory stimuli,
      further investigations are needed into why this should not occur in the situation
      of chronic mucous stasis which is the hallmark of PCD.

PMID- 19382501
TI  - Postoperative maxillary sinus mucocoele: risk factors for restenosis after
      surgery and preventive effects of mytomycin-C.
AB  - OBJECTIVE: To evaluate the clinical factors associated with restenosis after the
      surgery for treating postoperative maxillary sinus mucocoele and the preventive
      effect of topically applied mytomycin-C (MMC) on the restenosis. METHODS: This
      double-blinded randomized controlled prospective study included 38 cases of
      postoperative maxillary sinus mucocoeles. The patients underwent inferior meatal
      antrostomy with or without Caldwell-Luc operation, and cotton-pledgets soaked
      with MMC or normal saline were applied to the antrostomy sites for 5 minutes. The
      degree of narrowing of the opening and its correlation with the preoperative
      characteristics, including age, gender, allergy, presence of polyps, interval
      between previous surgery and computed tomography findings were evaluated.
      RESULTS: Three months after the surgery, the openings were patent in 24 cases,
      narrowed in 5 cases and stenotic in 9 cases. MMC application, septation of
      mucocoele and concurrent inflammation at the lesion side all had a significant
      effect on stenosis of the antrostomy site at 3 months after the surgery (p <
      0.05, Chi-square test). CONCLUSIONS: MMC has a favorable effect in preventing
      narrowing of the opening after surgery for maxillary sinus mucocoeles. The
      presence of septa in the mucocoeles or concurrent inflammation in the ipsilateral
      sinuses has an effect to promote restenosis.

PMID- 19382502
TI  - The effect of N-acetylcysteine on epistaxis and quality of life in patients with
      HHT: a pilot study.
AB  - BACKGROUND: Free O2- radicals may cause precapillary sphincter abnormalities,
      resulting in epistaxis in hemizygous knockout mice for Endoglin. The objective of
      this study was to test if antioxidants, like N-acetylcysteine (NAC), are have a
      role in the treatment of epistaxis in hereditary hemorrhagic telangiectasia
      (HHT). METHODS: Forty-three patients participated in this study taking NAC 600 mg
      t.i.d for 12 weeks. Patients registered frequency, severity and duration of
      epistaxis and private and work-related quality of life (QOL), using a diary for
      two 6 weeks periods. The first period was prior to starting treatment and the
      second started after 6 weeks using NAC. RESULTS: There was a decrease infrequency
      (p < 0.01) and severity (p < 0.01) of epistaxis during the day. The improvement
      was most remarkable in male patients and patients with an ENDOGLIN mutation. In
      women and patients with an ALK-1 mutation, only a trend for improvement was
      found. Nocturnal epistaxis did not improve. The effect of epistaxis on the
      ability to work (p = 0.02) was reduced. CONCLUSION: This pilot study was
      conducted to investigate whether animal experiments can be translated to humans
      with HHT regarding epistaxis. The positive results with NAC are promising and
      justify a randomised clinical trial.

PMID- 19382503
TI  - Dynamic infrared thermography of the nasal vestibules: a new method.
AB  - OBJECTIVE: The surface temperature distribution within the nasal vestibule and
      the nasal cavity strongly depends on the exact intranasal detection site and
      point of time during the respiratory cycle. Therefore, conventional temperature
      measurements e.g. with thermocouples only provide selective measurements. The use
      of infrared thermography cameras could present a new contactless method with a
      high spatiotemporal resolution. The aim of the present study was to evaluate the
      use of infrared thermography camera systems for measurements of the nasal surface
      temperature during respiration. METHODS: The surface temperature profiles within
      the nasal vestibules of healthy volunteers were recorded with infrared
      thermography cameras during several breathing cycles. Two different types of
      infrared thermography standard systems were used. RESULTS: The recordings allowed
      a display of temperature alterations within the nasal vestibules in a high
      spatiotemporal resolution synchronous to the breathing cycle. During inspiration,
      the vestibular surface cooled down presenting a non-homogenous distribution
      (range, 24.7 to 30.2 degrees C). During expiration, the vestibular surface was
      warmed again with a non-homogenous distribution (range, 33.1 to 36.2 degrees C).
      The results of both camera systems were comparable. CONCLUSION: Infrared
      thermography cameras allow the exact mapping of nasal surface temperature within
      the nasal vestibules with a high spatiotemporal resolution without surface
      contact.

PMID- 19382504
TI  - Rhinology resources on the internet: an update.
AB  - AIM: There has been a significant increase in the number of clinically useful
      biomedical resources available through the Internet over the last few years. The
      aim of this article is to present an updated list of all the worldwide web sites
      of rhinology. METHODS: All rhinologic links, which appear on the web site of the
      journal "Rhinology" were accessed and updated. Non-responding links were
      discarded and a new extensive survey of all rhinologic sites on the Internet was
      performed using on-line available search engines. All sites were accessed more
      than once at different times and their uniform resource locator (URL) address was
      recorded. RESULTS: The URL addresses of all rhinologic sites on the Internet
      appear in categories. Main categories include endoscopy and operative techniques,
      allergy, olfaction, rhinology clinics and research centers, organizations and
      societies, scientific journals, discussion groups, news and medical conferences,
      collective otolaryngology resources, and miscellaneous other sites of interest to
      rhinologists. CONCLUSIONS: This paper summarizes several types of resources
      available to rhinologists on the Internet. A complete universal list was
      composed, in which links to almost all interesting rhinologic links were
      included.

PMID- 19382505
TI  - Frontal mucocoele communicating with an arachnoid cyst of the anterior cranial
      fossa.
AB  - Mucocoeles usually involve the frontal sinus and can extend to the orbit or
      intracranially. In this case symptoms and radiological findings were typical of a
      left frontal mucocoele with intracranial extension. Intraoperative findings were
      compatible with a left frontal mucocoele communicating with an arachnoid cyst of
      the anterior cranial fossa.

PMID- 19382506
TI  - Cavernous sinus thrombosis secondary to allergic fungal sinusitis.
AB  - Cavernous sinus thrombosis (CST) is a rare and serious complication secondary to
      invasive fungal sinusitis, but rarer still in cases of allergic fungal sinusitis.
      Current recommendations for cavernous sinus thrombosis are controversial,
      especially regarding anticoagulation, secondary to the rarity of the diagnosis.
      Early surgical debridement and intravenous antibiotics are crucial to prevent
      mortality and decrease morbidity. Because thrombosis is thought to be caused by a
      bacterial superinfection, which follows a response to Aspergillus, antifungals
      may not be necessary. Despite the controversy, most physicians opt to treat with
      anticoagulation.

PMID- 19382507
TI  - Increasing access to evidence.

PMID- 19382508
TI  - Agency and engagement: older adults' experiences of participation in occupation
      during home-based rehabilitation.
AB  - BACKGROUND: Participation is considered the main goal of rehabilitation and
      occupational therapy intervention. This study focuses on older
      adults'participation in occupations in daily life when receiving home-based
      rehabilitation. PURPOSE: To explore how older adults with disabilities
      participate in daily life subsequent to hospitalization. METHODS: A prospective
      case-orientated design was used, with repeated interviews with three older adults
      and a constant comparative method of analysis. FINDINGS: Two main categories
      emerged as the participants' experience of participation: "Continuing to be an
      agent in daily life"captured the participants' decision making, choosing, and
      acting in daily life. "Life itself is the agent" identified how the participants,
      despite their strong wishes to be agents, also could let their participation be
      directed by their engagement in ongoing daily life. IMPLICATIONS: The findings
      identified participation as a dynamic engagement ranging from individual agency,
      including decision-making, choosing, and acting in daily life, to letting life
      itself be the agent. The emphasis on agency in the participants' experiences
      challenges rehabilitation professionals to find further means of facilitating the
      clients' possibilities of being agents in their daily lives.

PMID- 19382509
TI  - [Participation in leisure activities by patients with hemiplegia is greatly
      reduced].
AB  - BACKGROUND: Participation in leisure activities by people with hemiplegia is
      greatly reduced. There is limited information regarding the extend to which
      client participation is taken into consideration in the current practice of
      occupational therapy. PURPOSE: The purpose of this study is to examine the way by
      which occupational therapists working at the Centres medico-sociaux (CMS) Vaudois
      take into consideration the leisure activities of people with hemiplegia.
      METHODS: An investigation was undertaken by correspondence with occupational
      therapists working at the CMS. Of the 54 questionnaires received, 31 were
      considered for analysis. RESULTS: The majority (87 %) of participating
      occupational therapists explore the areas of leisure activities. Objectives
      linked to this field are achieved by 55% of the clients. Diverse interventions
      are favoured in order to reach these objectives. CONCLUSION: Occupational
      therapists appear to frequently address the subject of leisure activities with
      their clients. However, they identify objectives with only a limited percentage
      of their clients and utilise few of the available resources in order to reach
      these objectives.

PMID- 19382510
TI  - Individualized outcome measures for evaluating life skill groups for children
      with disabilities.
AB  - BACKGROUND: The challenge of evaluating life skill groups is the need to assess
      skills reflecting the priorities and abilities of the individuals as well as the
      program focus. PURPOSE: This study describes the feasibility and utility of goal
      menus and individualized outcome measures in two life skill groups for children
      with disabilities. METHODS: Eleven children were evaluated at baseline and 5
      weeks post-program using a modified Canadian Occupational Performance Measure
      (COPM) and modified Goal Attainment Scaling (mod-GAS). FINDINGS: COPM
      satisfaction median scores across all goals increased post-program by 3.0 points
      (P=0.001) and performance scores by 1.0 point (P=0.002). Mod-GAS scores for all
      participants were at least -1 (partial achievement), and 55% of participants
      achieved their functional goal (Mod-GAS = 0) with carryover into their community
      environments. IMPLICATIONS: This study supports the positive contribution of
      individualized measures to evaluate outcomes within life skill programs for
      children with disabilities.

PMID- 19382511
TI  - Applicability and clinical utility of the Client-Centred Strategies Framework.
AB  - BACKGROUND: The Client-centred Strategies Framework consists of strategies for
      facilitating therapists' application of client-centred approaches. PURPOSE: The
      purpose of this study was to explore the application of the strategies and the
      utility of the framework to implement client-centred approaches. METHODS: The
      study used a sequential mixed-methods procedure. The quantitative phase consisted
      of a survey of 230 Canadian occupational therapists. The qualitative phase
      consisted of telephone focus groups with a sample of 14 Canadian respondents to
      the initial survey. FINDINGS: Results indicated that occupational therapists
      experience challenges in implementing strategies, particularly related to
      community organizing, coalition advocacy, and political action. Therapists
      identified multiple factors that influenced the implementation of strategies and
      ways of incorporating strategies into daily practice. The Client-centred
      Strategies Framework was viewed as a useful tool for increasing dialogue about
      occupational therapists' role in client-centred practice. IMPLICATIONS: The
      results of this study encourage an expanded view of client-centred strategies and
      the application of strategies to daily practice.

PMID- 19382512
TI  - Qualitative meta-synthesis: reflections on the utility and challenges in
      occupational therapy.
AB  - BACKGROUND: A qualitative meta-synthesis is an approach to synthesizing relevant
      findings from across qualitative studies on a particular topic using methods
      consistent with qualitative research. PURPOSE: Using examples of recently
      completed qualitative meta-synthesis projects, the purpose of this paper is to
      present the meta-synthesis approach; highlight the key steps, processes, and
      issues involved; and demonstrate its potential to advance knowledge about
      occupation and occupation-based practice. KEY ISSUES: The qualitative meta
      synthesis approach allows us to take stock of the current state of knowledge in a
      given area in order to ensure that we have explored the phenomenon from different
      perspectives and to begin to push the field forward by allowing us to develop
      deeper insights and understandings. IMPLICATIONS: Despite certain limitations and
      challenges associated with the approach, qualitative meta-syntheses can provide
      new knowledge through critical analysis and interpretation to inform client,
      practitioner, and policy audiences.

PMID- 19382513
TI  - Improving transitions to reduce readmissions.
AB  - Delivering high quality healthcare requires crucial contributions from many parts
      of the care continuum. However, as healthcare becomes increasingly specialized,
      coordination between providers and between settings is too often not conducted as
      a team effort. In the hospital setting, poor coordination of care often results
      in hospital readmissions, many of which are avoidable. In this article, we
      describe processes that hospitals can implement immediately to dramatically
      improve care transitions and reduce re-hospitalization rates. Readmission rates
      are a focus of interest for payers and policymakers seeking to promote efficiency
      and quality. Hospital executives may want to prepare their organization to excel
      on this performance metric in anticipation of payment, policy, and/or other
      forecasted changes in the market.

PMID- 19382514
TI  - Better transitions: improving comprehension of discharge instructions.
AB  - Discharge out of the hospital is a time of heightened vulnerability for our
      patients. The combination of shorter lengths of stay and increased clinical
      acuity results in increased complexity of discharge instructions and higher
      expectations for patients to perform challenging self-care activities. Yet, the
      amount of time and resources available for patient and family caregiver
      preparation prior to discharge has not significantly changed commensurate with
      these new demands. Inadequate health literacy and unrecognized cognitive
      impairment are two important contributing factors. In this article we discuss the
      effects of health literacy and cognitive impairment on patient comprehension of
      discharge instructions, how this may impact the frequency of adverse events after
      they leave the hospital, and likelihood of readmission, and offer an evidence
      based prototype for how to address the problem.

PMID- 19382515
TI  - Sealing the cracks, not falling through: using handoffs to improve patient care.

PMID- 19382516
TI  - Come together, right now.

PMID- 19382517
TI  - Better coordination of care reduces readmissions.

PMID- 19382518
TI  - Early effects of low benzene exposure on blood cell counts in Bulgarian
      petrochemical workers.
AB  - OBJECTIVES: Only few studies have examined early hematological effects in human
      populations exposed to low benzene levels and their findings are controversial.
      We evaluated hematological outcomes (WBC, neutrophils, lymphocytes, monocytes,
      eosinophils, basophils, RBC, Hb, HCT MCV, platelets and MPV) in a population of
      153 Bulgarian petrochemical workers exposed to benzene (range 0.01-23.9 ppm) and
      50 unexposed subjects. METHODS: Written informed consent was obtained and a self
      administered questionnaire used to collect information on current smoking habits,
      lifestyle, and occupational activities. Exposure assessment was based on personal
      monitoring sampling the day before phlebotomy. Urinary trans-trans-muconic acid
      (t,t-MA) was determined at the beginning and end of the work shift. Based on
      individual airborne benzene measurements, study subjects were categorized in
      three exposure categories (referents, <1 and > or =1 ppm). Mean values of each
      hematologic outcomes in each exposure category were compared with the referent
      group using a multiple linear regression model adjusted for age, gender, current
      smoking habits and environmental toluene level. The influence of the CYP2E1 (RsaI
      and DraI) and NQO1 609C>T genetic polymorphisms on differential hematological
      parameters was also investigated. RESULTS: No dose-response effect was observed
      for most of the examined hematological outcomes (WBC, lymphocytes, neutrophils,
      monocytes, RBC, Hb, HCT, MCV, platelets and MPV). The eosinophil count was
      inversely related to benzene exposure only among smokers. Conversely, basophils
      increased with increasing exposure. No effect on benzene hematotoxicity was found
      for any of the investigated polymorphisms. CONCLUSION: In our study we did not
      find a decline in WBC and lymphocytes related to benzene exposure. A
      myeloproliferative effect of benzene is highly unlikely to explain the observed
      reduction in eosinophils and increase in basophils as it would lead to a
      concordant depression in all granulocyte subpopulations. Whether benzene effects
      at low doses are present in Caucasian populations remains uncertain, thus
      warranting further investigations.

PMID- 19382519
TI  - [Academic occupational medicine].
AB  - This assay analyses the sorry state of occupational medicine, particularly in
      Italian Academy, and discusses the opportunities for its revitalization. Contrary
      to its past history, occupational medicine is only witnessing the ongoing
      extraordinary revolution in biomedical sciences and taking no advantage from it.
      The main reason for this academic decline may be due, paradoxically, to its
      success. The change of paradigm, from clinical medicine to preventive activities
      was relatively quick, missing a clear understanding of their differences in
      backgrounds, methods and objectives. Moreover, the spread of different
      disciplines across occupational medicine has led to an impoverish role of
      biomedical sciences and to diminished medical skills of occupational physicians.
      The wide range of opportunities offered by translational medicine gives to the
      discipline unprecedented chances of revitalization.

PMID- 19382520
TI  - [Post-traumatic stress disorder following robbery at the workplace: a pilot study
      on 136 pharmacy workers].
AB  - INTRODUCTION: Robbery at the place of work is one of the most common traumatic
      events in both developed and developing countries. Italy is one of the European
      countries with a medium-to-high prevalence and pharmacy and bank employees are
      particularly at risk. Research on the psychological effects on workers who are
      victims of robbery is scarce when compared with traditional trauma studies.
      OBJECTIVE: To assess the association between workplace robbery, Post-traumatic
      Stress Disorder (PTSD), quality of life and work ability in a sample of Italian
      pharmacy workers. METHODS: 136 pharmacy workers--90 robbery victims and 46 non
      victims--were recruited from the Milan area. They completed a questionnaire
      including: socio-demographic characteristics, robbery history and description, a
      self-report version of the Clinician Administered PTSD Scale (CAPS-I), General
      Health Questionnaire (GHQ), Beck Depression Inventory (BDI), Work Ability Index
      (WAI), Short Form 36 Health Survey Questionnaire (SF-36). RESULTS: No differences
      were found between victims and non-victims for GHQ and BDL; WAI scores of victims
      were significantly lower than non-victims. Exposure to robberies was associated
      with lower WAI in a multivariate analysis; 10 victims reported PTSD and much
      lower WAI and SF-36, higher GHQ and BDI than non-PTSD victims. CONCLUSIONS:
      Workplace robbery has a mild but long-lasting effect on workers' ability to work.
      For a significant proportion of victims, robbery exposure is associated with the
      onset of PTSD, with increased risk for severe and long-lasting impairment of
      emotional well-being, quality of life and work ability. Early intervention
      programmes at the workplaces aimed at promoting a more rapid recovery after a
      traumatic event are needed.

PMID- 19382521
TI  - Intention to leave nursing in a major Milan hospital: current situation and
      future perspectives.
AB  - BACKGROUND: European nurses manifest a significant tendency to leave nursing,
      with Italy in second place after the United Kingdom. It is therefore necessary to
      address the problem in national and local settings and to identify possible areas
      of intervention. OBJECTIVES: This paper discusses the results of a survey carried
      out in a major hospital in Milan (Italy) aimed at finding solutions to the above
      problem. METHODS: In 2004 a questionnaire was administered to the entire nursing
      staff. Associations between intention to quit, socio-demographic variables and
      job characteristics were verified by means of Mann-Whitneys's and Kruskall
      Wallis' tests, Spearman's correlation coefficients and logistic regression.
      RESULTS: Nearly 60% of nurses considered leaving, at least every now and then.
      The tendency to quit was associated with job dissatisfaction, burnout symptoms
      and the job market situation. For those for whom nursing had a moral value, the
      tendency to quit was less marked. Characteristics such as regularity of shifts,
      type of ward, type of contract and number of working hours did not show any
      statistically significant association with tendency to quit. CONCLUSIONS: There
      are many organizational aspects that may be of importance in influencing nurses'
      intention to leave the profession. Efforts are needed to re-define the role of
      nurses in healthcare organization, adjusting salaries to the actual cost of
      living and preventing conditions that could lead to psychological exhaustion.
      Mentorship could also be useful for a better integration of nurses in hospital
      wards.

PMID- 19382522
TI  - [Mesothelioma in construction workers: risk estimate, lung content of asbestos
      fibres, claims for compensation for occupational disease in the Veneto Region
      mesothelioma register].
AB  - BACKGROUND: Work in the construction industry is causing the highest number of
      mesotheliomas among the residents of the Veneto Region (north-east Italy, 4,5
      million inhabitants). OBJECTIVES: To sum up the results on occurrence, asbestos
      exposure, lung fibre content analyses, and compensation for occupational disease.
      METHODS: Case identification and asbestos exposure classification: active search
      of mesotheliomas that were diagnosed via histological or cytological examinations
      occurring between 1987 and 2006; a probability of asbestos exposure was
      attributed to each case, following interviews with the subjects or their
      relatives and collection of data on the jobs held over their lifetime. Risk
      estimate among construction workers: the ratio between cases and person-years,
      the latter derived from the number of construction workers reported by censuses.
      Lung content of asbestos fibres: examination of lung specimens by Scanning
      Electron Microscope to determine number and type of fibres. Claims for
      compensation and compensation awarded: data obtained from the National Institute
      for Insurance against Occupational Diseases available for the period 1999-2006.
      RESULTS: of 952 mesothelioma cases classified as due to asbestos exposure, 251
      were assigned to work in the construction industry (21 of which due to domestic
      of environmental exposures), which gives a rate of 4.1 (95% CI 3.6-4.8) x 10(5) x
      year among construction workers. The asbestos fibre content detected in the lungs
      of 11 construction workers showed a mean of 1.7 x 10(6) fibres/g dry tissue
      (range 350,000-3 million) for fibres > 1 micro, almost exclusively due to
      amphibole fibres. 62% of the claims for compensation were granted but the
      percentage fell to less than 40% when claims were submitted by a relative, after
      the death of the subject. CONCLUSION: The prevalence of mesothelioma occurring
      among construction workers is high and is associated with asbestos exposure; the
      risk is underestimated by the subjects and their relatives. All mesotheliomas
      occurring among construction workers should be granted compensation for
      occupational disease.

PMID- 19382523
TI  - Respiratory function in wind instrument players.
AB  - BACKGROUND: The playing of wind instruments has been associated with changes in
      respiratory function. STUDY OBJECTIVES: To investigate the effect of playing wind
      instruments on lung function and respiratory symptoms. METHODS: The present study
      included 99 wind instrument players and a group of 41 string instrument players
      as a control from 3 major orchestras in Zagreb, Croatia. Data on chronic
      respiratory symptoms were recorded in all studied subjects. Lung function was
      measured in wind instrument players by recording maximum expiratory flow-volume
      curves. RESULTS: Wind instrument players demonstrated significantly higher
      prevalences of sinusitis, nasal catarrh and hoarseness compared to control
      musicians. One wind instrument player developed asthma associated with his work.
      Odds ratios for wind instrument players were significant for chronic cough,
      chronic phlegm and chronic bronchitis by smoking habit (p<0.05 or p<0.01) but not
      for length of employment. Ventilatory capacity data indicate that wind instrument
      players had significantly greater FEV1 (smokers and nonsmokers) as well as FEF50
      (nonsmokers) (p<0.05) compared to predicted values. Regression analysis of
      pulmonary function tests in wind instrument players demonstrate a significant
      link between FEV1 and FEF50 and length of employment. Those wind instrument
      players with longer employment had the greatest increases in lung function.
      CONCLUSIONS: Our data suggest that musicians playing wind instruments may be
      susceptible to chronic upper airway symptoms. Interestingly wind instrument
      playing may be associated with higher than expected lung function parameters.

PMID- 19382524
TI  - [Ergonomic assessment of technical improvements in the work of manual labourers
      of a porphyry quarry].
AB  - BACKGROUND: Previous investigations have shown an excess of musculoskeletal
      disorders in quarry workers referable to awkward postures and lifting of heavy
      weights. Recently several sorts of workbenches equipped with conveyor belts were
      introduced in order to improve job postures and, therefore, safety. METHODS:
      Using the OWAS method we investigated the postures of quarry workers using two
      technologically different workbenches which were compared with the traditional
      working method (completely manual). RESULTS: Use of workbenches allows quarry
      workers to work standing with the back on a vertical axis and legs infirm and
      stable position. CONCLUSIONS: According to the OWAS method most postures adopted
      in traditional working methods involve a high risk, whereas with the use of
      workbenches most of these high risk postures are reclassified and no longer
      require urgent ergonomic redesign. Technical innovations (such as lifting
      platforms and air suction pad winches) allow workplaces to be planned depending
      on the size and weight of the stone materials obtained from the quarry face.

PMID- 19382525
TI  - [Cervical disorders in a group of male workers not exposed to physical ergonomic
      risk].
AB  - OBJECTIVES: The aim of our study was to assess the prevalence of neck pain in the
      working population not exposed to ergonomic risks. METHODS: A total of 373 male
      workers were recruited in the Venice area of Italy. The inclusion criterion was
      the absence of exposure to ergonomic risk factors at the workplace. We collected
      the data via interviews between March 2004 and December 2006 conducted by
      properly trained operators. The prevalence of neck pain episodes was calculated
      after selecting 347 subjects without functional outcomes for severe trauma or
      genetic and degenerative diseases involving the same anatomical area. The
      strength of the association of neck pain with the collected variables was tested
      by means of logistic regression analysis. RESULTS: The group had a good attitude
      to doing physical activity in their free time. Exposure to high stress at work
      involved 12% of the sample. Multivariate analysis suggested a more than 3-fold
      level of risk among individuals with high levels of stress at work. The O.R. was
      3.51 for those suffering from back pain at the same time and 6.85 for those who
      reported shoulder pain. CONCLUSIONS: Our study, in agreement with the scientific
      literature, showed evidence of increased risk of neck pain in subjects exposed to
      stress. There was a clear association with neck pain and joint disorders of other
      areas of the spine and shoulder. The results showed that the quantification of
      painful joint disorders, considering the numerical importance and the brief
      latency, is well suited to models of cross sectional studies.

PMID- 19382526
TI  - A historical sketch; life and time of Jonathan Hutchinson (1828-1913), the first
      sarcoidologist.
AB  - In the years preceding and following the turn of the 19th century several
      publications appeared independently that drew attention to what is now regarded
      as sarcoidosis. The first recorded and illustrated example is attributed to
      Jonathan Hutchinson of London. It appeared in Illustrations of Clinical Surgery
      (1877).

PMID- 19382527
TI  - Inhibitors of tumor necrosis factor (TNF) in sarcoidosis: who, what, and how to
      use them.
AB  - Sarcoidosis patients with chronic disease often require prolonged treatment.
      Although alternatives to corticosteroids have been frequently administered in
      this disease, corticosteroids remain the mainstay of treatment. However disabling
      side effects which accompany prolonged treatment can necessitate the use of
      alternative, steroid-sparing agents. The tumor necrosis factor (TNF) inhibitors
      can be useful in treating chronic sarcoidosis. Among the biologic agents which
      inhibit TNF, infliximab has been studied most extensively in sarcoidosis with
      fewer reports available for adalimumab and etanercept. This review will summarize
      the available evidence to identify the best candidate to receive an anti-TNF
      regimen as well as the relative benefits and side effects of the three anti-TNF
      biological agents for treating sarcoidosis. A stepwise approach is proposed to
      increase the likelihood of disease improvement for patients who experience an
      inadequate response to an anti-TNF agent.

PMID- 19382528
TI  - Differentiation of sarcoidosis from tuberculosis using real-time PCR assay for
      the detection and quantification of Mycobacterium tuberculosis.
AB  - BACKGROUND: The clinical and pathological features of sarcoidosis and
      tuberculosis may mimic each other, and when the caseous necrosis is not seen in
      tuberculosis tissue, differentiation is not easy. OBJECTIVE: This study evaluates
      the ability of real-time PCR quantification and sets the quantitive value to
      differentiate sarcoidosis from TB. METHODS: Formalin-fixed and paraffin-embedded
      sections of biopsy samples, from 104 patients with sarcoidosis, 31 patients with
      tuberculosis, and 55 controls with other respiratory diseases (26 with
      nonspecific lymphadenitis and 29 with emphysema bullae), were collected to
      amplify insertion sequence IS986 of Mycobacterium tuberculosis (MTB) genome by
      real-time quantitative PCR. The diagnostic performance of qualitative and
      quantitative analysis of real-time quantitative PCR was assessed by receiver
      operating characteristic (ROC) curves. RESULTS: MTB DNA was detected in 20 of the
      104 sarcoidosis samples and 7 of the 55 control samples, but was detected in all
      of the 31 tuberculosis samples. The numbers of MTB genomes were 0-4.71x10(3)
      copies per ml in sarcoidosis samples, 1.58x10(2)-5.43x10(7) copies per ml in
      tuberculosis samples and 0-1.02x10(3) copies per ml in controls with quantitative
      analysis. Receiver-operating characteristic (ROC) curves showed that MTB genome
      quantification had greater diagnostic performance than MTB genome qualitation in
      discriminating patients with sarcoidosis from those with tuberculosis (area under
      the ROC curves: 0.994 vs 0.904, P<0.001). The sensitivity and specificity of
      qualitative analysis were 100% and 80.8% respectively. At cutoff value of
      1.14x10(3) copies per ml for MTB genome quantification, the sensitivity was 96.8%
      and specificity was 98.1%. CONCLUSIONS: The real time PCR quantification is a
      valuable test for differentiation between sarcoidosis and tuberculosis, and the
      MTB genome copies number of 1.14x10(3) copies per ml should be preferred as
      quantitative cutoff value for the differentiation.

PMID- 19382529
TI  - M. avium binding to HLA-DR expressed alleles in silico: a model of phenotypic
      susceptibility to sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatosis disease of unknown origin where a number
      of microbes, in particular M. tuberculosis and non-tuberculous mycobacteria, have
      been hypothesized to play a role in disease pathogenesis, possibly through
      bacterial antigen-driven hypersensitivity. To test this concept, we used
      bioinformatic tools allowing the identification of antigenic peptides in whole
      microbial genomes to analyze the interaction between the expressed HLA-DR gene
      allelic variants and the HLA-DR immunome of all pathogenic bacteria in a
      population of 149 sarcoidosis affected subjects and 447 controls, all HLA-typed
      at high resolution. We show here that patients with the Lofgren's syndrome,
      express HLA-DR alleles that recognize in silico a significantly higher number of
      bacterial antigen epitopes compared to the control population (18,496+9,114 vs
      17,954+8,742; p<0.00001), and the chronic sarcoidosis affected population
      (17,954+8,742; p<0.00001 vs Lofgren's and controls). Further, the analysis of the
      ability of the HLA-DR allele combinations expressed by the Lofgren's and the
      chronic sarcoidosis affected subjects to recognize M. avium epitopes demonstrates
      that a significantly larger number of Lofgren's are capable of top affinity
      recognition, compared to chronic sarcoidosis (45% vs 17%, p<0.0037). Finally,
      both Lofgren's and chronic sarcoidosis subjects expressed HLA-DR allele
      combinations capable of M. tuberculosis and M. avium epitope recognition at
      higher affinity than tuberculosis affected subjects (p<0.01 all comparisons). In
      conclusion, we propose that - at least in a subgroup of affected subjects -
      sarcoidosis might be part of a spectrum of granulomatous responses to several
      agents where the Lofgren's syndrome represents the hyper-reactive end of the
      spectrum while pulmonary tuberculosis and atypical mycobacterial infections might
      represent the opposite end.

PMID- 19382530
TI  - Bronchiolitis obliterans syndrome and survival following lung transplantation for
      patients with sarcoidosis.
AB  - BACKGROUND: End-stage sarcoidosis is characterized by severe pulmonary fibrosis
      and is often poorly responsive to medical therapy. Lung transplantation,
      therefore, may be the only treatment option. Currently, there are few studies
      evaluating long-term outcomes following transplantation for these patients. Our
      aim was to evaluate post-transplant morbidity and survival of patients with
      sarcoid compared to recipients transplanted for idiopathic pulmonary fibrosis
      (IPF). METHODS: We retrospectively examined 300 lung transplant recipients using
      a dedicated database. Over a 10-year period, 15 (5.0%) patients with sarcoidosis
      and 48 (16%) patients with IPF were identified. Primary outcome measures included
      rate and time to onset of bronchiolitis obliterans syndrome (BOS) and survival.
      RESULTS: Recipients in the sarcoid group were younger and predominantly female
      compared to recipients in the IPF group. Five of 15 (33%) sarcoid patients
      developed BOS versus 15 of 48 (31%) IPF patients (p=1.0). There was no
      significant difference in the time to BOS onset. Median survival was 1,365 days
      for the sarcoid group and 1,593 days for the IPF group (Hazard Ratio 0.94 by
      Kaplan-Meier analysis; [95% CI] 0.33-2.67; p = 0.90). CONCLUSIONS: We observe
      similar long term outcomes following lung transplantation for sarcoid and IPF
      recipients. Transplantation remains a treatment option for end-stage sarcoidosis,
      as BOS and survival rates are comparable to IPF.

PMID- 19382532
TI  - Effects of oxygen on exercise-induced increase of pulmonary arterial pressure in
      idiopathic pulmonary fibrosis.
AB  - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a severe disease with no
      known effective therapy. Patients with IPF may develop severe increase of
      pulmonary arterial pressure (PAP) on exercise, the mechanisms of which is not
      clearly identified. OBJECTIVES: To determine whether oxygen may correct the
      increase of PAP developed during exercise in patients with IPF. PATIENTS AND
      METHODS: We performed a prospective study on patients with IPF and no hypoxaemia
      at rest. The absence of pulmonary hypertension (PH) at rest was confirmed by
      echocardiography (systolic PAP <35 mmHg). Eight patients underwent
      echocardiography during exercise in air and with oxygen (to maintain saturation
      of at least 94%). Right ventricle-right atrium gradient and cardiac output were
      measured at rest, after each increment and at peak. We then compared the
      echocardiographic results obtained for air and oxygen. RESULTS: All patients
      developed significant increase of SPAP on exercise (73 +/- 14 mmHg in air).
      Oxygen did not significantly improve SPAP on exercise (SPAP: 76 +/- 15 mmHg).
      Echocardiographic characteristics were similar between air and oxygen except for
      exercise tolerance in term of workload (p=0.045) and endurance (p=0.017). Resting
      pulmonary function tests did not predict the occurrence of increase of PAP on
      exercise. CONCLUSION: Our results demonstrate that oxygen does not improve
      exercise-induced increase of PAP in patients with IPF and support the hypothesis
      that hypoxic vaso-constriction is not the main mechanism of acute increase of PAP
      during exercise.

PMID- 19382531
TI  - HLA and environmental interactions in sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatosis of unknown etiology despite being
      described over 100 years ago. While both genetic predisposition and environmental
      exposures have been proposed as playing a role in this disease, there have not
      been any systematic investigations of gene-environmental interaction in this
      disease. In the ACCESS dataset, detailed environmental histories and high
      resolution HLA class II typing were performed on 476 cases of newly diagnosed
      sarcoidosis and 476 matched controls from the patients' community. We evaluated
      gene-environmental interactions in exposures or HLA class II alleles that were
      present in > 5% of the population and had an odd ratio of > 1.0. Four exposures
      and four HLA Class II alleles met these criteria and were evaluated. Significant
      interaction was observed between HLA DRB1*1101 and insecticide exposure at work
      (p < 0.10) and suggestive interaction was observed between HLA DRB1*1101 and
      exposure to mold and musty odors and DRB1*1501 and insecticide exposure at work
      (P < 0.15). In addition, HLA DRB1*1101 and insecticide exposure at work was
      associated with extrapulmonary sarcoidosis, specifically cardiac sarcoidosis and
      hypercalcemia (p<0.05) and HLA DRB1*1101 and exposure to molds and musty odors
      was associated with pulmonary only sarcoidosis (P < 0.05). These studies suggest
      that sarcoidosis is due to an interaction of genetic predisposition and
      environmental exposure in at least some cases of sarcoidosis. Future studies in
      defined phenotypes of sarcoidosis may be necessary to define environmental and
      genetic associations with sarcoidosis.

PMID- 19382533
TI  - Improvement of cardiac sympathetic nerve function in sarcoidosis.
AB  - Some patients with sarcoidosis can have cardiac involvement. Impairment of the
      cardiac sympathetic nerve activity is seen in about 50% of the sarcoidosis
      patients with small fiber neuropathy. In this case we present a sarcoidosis
      patient with small fiber neuropathy and cardiac symptoms with a cardiac
      sympathetic dysfunction, assessed with I-123 MIBG SPECT. After 5 months of
      treatment with carvedilol, which has besides adrenergic receptor blocking effects
      also antioxidant action, we saw a clear improvement of the cardiac sympathetic
      function demonstrated on a repeated I-123 MIBG SPECT. Future studies should
      explore the clinical relevance of the relation of oxidative stress, antioxidant
      therapy and cardiac dysfunction in sarcoidosis.

PMID- 19382534
TI  - 18F-FDG PET in sarcoidosis: an observational study in 12 patients treated with
      infliximab.
AB  - BACKGROUND: 18F-FDG PET is a promising technique in sarcoidosis imaging, although
      it is not incorporated in routine activity assessment. The purpose of this study
      was to correlate 18F-FDG PET with standard sarcoidosis activity parameters during
      infliximab treatment. METHODS: Twelve patients with refractory sarcoidosis were
      treated with 6 cycles of infliximab. Pre- and post-therapy 18F-FDG PET was
      visually evaluated and SUVmax was measured. In addition, the effect of infliximab
      was evaluated by changes in symptoms, angiotensin converting enzyme (ACE),
      soluble interleukin-2 receptor (sIL-2R), vital capacity (VC), diffusion capacity
      of the lung for carbon monoxide (DLCO) and chest radiography. SUVmax and
      conventional parameters were correlated. RESULTS: Clinical improvement as judged
      by conventional parameters was seen in all patients, though with a minor response
      in one. Symptoms improved in 11/12 patients while chest radiographic stages did
      not change. The decrease in ACE was 39% and in sIL-2R 47% (p<0.01). Improvement
      of VC and DLCO was 5.4% and 3.3% (p<0.05), respectively. 18F-FDG PET revealed
      either improvement or normalization in 11/12 (92%) clinically responding
      patients. The overall decrease in SUVmax was 55% (p<0.01); the patient with a
      limited response showed a 34% increase. A decrease in SUVmax of the lung
      parenchyma correlated with an improvement of VC (r=-0.75, p<0.01). No significant
      correlation between SUVmax and other parameters was found. CONCLUSION: Changes
      imaged by 18F-FDG PET during infliximab treatment in sarcoidosis patients
      correlate with signs of clinical improvement to a considerate extent, which
      supports the hypothesis that 18F-FDG uptake represents disease activity.

PMID- 19382536
TI  - Pathophysiology of glaucoma and continuous measurements of intraocular pressure.
AB  - Glaucoma is a leading cause of visual impairment and blindness worldwide. The
      main risk factor for glaucoma is an elevated intraocular pressure (IOP), which is
      also the only currently treatable risk factor. Despite its importance, our
      understanding of IOP is incomplete and our ability to measure IOP is limited. IOP
      is known to undergo both random fluctuations as well as variations following a
      circadian pattern. In humans, IOP is highest at night and lower during the
      daytime, largely due to changes in body position, although other factors appear
      to contribute. In rabbits, IOP is also highest at night and lower during the day,
      likely due to circadian variations in sympathetic nervous system activity. Random
      and circadian IOP variations may be important to glaucoma pathogenesis,
      independent of the diurnal IOP level. However, due to limitations with current
      IOP measurement technology, clinical practice typically involves only a few IOP
      measurements per year. As well, current technology does not allow 24-hour
      monitoring of pressure without the use of sleep laboratories or hospital
      admission. Two strategies for automating IOP measurement are temporary (non
      invasive) monitoring and permanent (implantable) monitoring. Efforts at
      developing devices to allow continuous IOP monitoring have occurred for over 40
      years without producing a clinical device. Current technological progress would
      seem to suggest that such devices are possible at this time, and a review of
      previous attempts provides guidelines for their development.

PMID- 19382537
TI  - Specific expression of E-Tmod (Tmod1) in horizontal cells: implications in
      neuronal cell mechanics and glaucomatous retina.
AB  - Erythrocyte tropomodulin (E-Tmod) is a tropomyosin-binding and actin capping
      protein at the point end of the filaments. It is part of a molecular ruler that
      plays an important role in generating short actin protofilaments critical for the
      integrity of the cell membrane. Here, with the use of E-Tmod+/lacZ mice, we
      demonstrated a specific E-Tmod expression in horizontal cells (HCs) in the
      retina, and analyzed the stress-strain relationship of HCs, vertically oriented
      neurons, and retinal ganglial cells (RGC) under normal and high intraocular
      pressure (IOP). Since their dendrites are oriented laterally in a plane and form
      most complicated synapses with multiple cone photoreceptors, HCs are subjected to
      a greater stress and strain than vertically oriented neurons. The specific E-Tmod
      expression suggests its role in protecting HCs from mechanical damages in certain
      eye diseases, such as glaucoma, a neurodegenerative disease of the retina
      characterized by an elevated IOP. A stress-strain analysis on axons of RGC that
      run horizontally but only anchor at the optical nerve head suggests that they may
      also be subjected to a higher mechanical stress, which leads to an increase in
      "cup-to-disc" ratio in a higher IOP or in glaucoma patients.

PMID- 19382538
TI  - [A description of a population with severe oligodontia].
AB  - The dentition of 116 patients with a non-syndromic form of oligodontia was
      characterized. For this purpose use was made of the so-called Tooth Agenesis Code
      (TAC), with which the various patterns of missing teeth can be indicated with a
      unique number. Oligodontia can present itself in very diverse ways. Only 3
      patterns were seen (2 times) among these 116 patients. Considered per quadrant,
      in the upper jaw, on the one hand, agenesis of both premolars and the lateral
      incisor was most common and, on the other, the absence of all teeth except the
      central incisor and the first molar. In the lower jaw, agenesis of the second or
      of both premolars was most common. Evaluating treatments and formulating
      standards of restoration in the treatment of patients with severe oligodontia are
      methodological challenges. Homogeneous, comparable sub-groups of patients of any
      size are difficult to construct due to the low prevalence of severe oligodontia
      and the diversity of patterns of agenesis when the whole mouth is taken into
      consideration.

PMID- 19382539
TI  - [The effect of the risk of a complaint on treatment decision making. An
      explorative investigation in fourth-year dental students].
AB  - The perception of the seriousness of a false-negative or false-positive diagnosis
      could influence treatment decision making for carious lesions. In order to
      investigate this hypothesis, the perceived risk of a complaint at a disciplinary
      tribunal was used as an indicator of the seriousness of the consequences of
      treatment decision errors. Using a computer programme for caries diagnosis on
      radiographs and by means of a questionnaire, was investigated in a group of
      fourth-year dental students whether their accuracy of treatment decision making
      for carious lesions was dependent on the perception of the risk of a complaint at
      a disciplinary tribunal. The perception of the likelihood of complaints does not
      seem to play a significant role in the accuracy of decision making. However, the
      students demonstrated unrealistical high risk perceptions of a complaint at a
      disciplinary tribunal following a treatment decision making error by a false
      diagnosis of a carious lesion on a bitewing radiograph.

PMID- 19382540
TI  - [Standard dental care for people who are mentally disabled].
AB  - The Health Insurance Board (CVZ) initiated a study of the functioning of the
      dental care system for mentally disabled people in the Netherlands.Two
      independent samples were used for the study, each drawn from a subpopulation of
      people with a mental disability in the age-group 15-45: people who have always
      lived at home (n = 60) and people who have been at some time been
      institutionalized and as a result of decentralization now live outside of the
      institution (n = 52). Dental visits were in both samples remarkably frequent (95
      100%) and relatively few problems with daily dental care were identified.
      However, the health insurance regulations were unclear to many parents and
      carers, and there were doubts regarding dentists' specific expertise. At first
      sight the results of this study do not give cause to assume that there are
      special barriers to access to professional dental care for adult people with
      special needs. For a definitive conclusion regarding the long-term effects of the
      implementation of policies to de-institutionalize disabled people, and their
      influence on quality of care, a longitudinal evaluation of the oral health status
      is required.

PMID- 19382541
TI  - [Dentistry and society].
AB  - In an editorial in the British Dental Journal (2007) E.J. Kay raised the question
      whether dentist-general practitioners have to be educated in dental schools
      affiliated with (academic) hospitals. Her hypothesis is that some 95% of
      graduating dentists enter in general practice and that the educational
      environment therefore should be there as well. In the present reaction it is
      argued that this is a bad idea because the complete separation of dental
      education from the academic medical environment would mean a drastic and
      undesirable limitation and impoverishment of the curriculum. At the same time it
      is not denied that outreach programmes in a dental school curriculum can be very
      meaningful.

PMID- 19382535
TI  - Creation of functional micro/nano systems through top-down and bottom-up
      approaches.
AB  - Mimicking nature's approach in creating devices with similar functional
      complexity is one of the ultimate goals of scientists and engineers. The
      remarkable elegance of these naturally evolved structures originates from bottom
      up self-assembly processes. The seamless integration of top-down fabrication and
      bottom-up synthesis is the challenge for achieving intricate artificial systems.
      In this paper, technologies necessary for guided bottom-up assembly such as
      molecular manipulation, molecular binding, and the self assembling of molecules
      will be reviewed. In addition, the current progress of synthesizing mechanical
      devices through top-down and bottom-up approaches will be discussed.

PMID- 19382542
TI  - [Dissertations 25 years after date 19. Children with a lateral forced bite].
AB  - Premature occlusal contacts may force the mandible into a not optimally
      functional intercuspal position, a so-called forced bite. When the mandible is
      forced laterally, it is called a lateral forced bite, more prevalent in children
      than in adults. In the PhD thesis (1983) 'Mandibular movement patterns: a
      methodological and clinical investigation of children with a lateral forced
      bite', open-close-clench cycles had been studied in 12 children with a lateral
      forced bite and in a control group of 6 children. Their mandibular movements were
      registered using an opto-electronic registration technique. Only in the children
      with a lateral forced bite, the mandible appeared to be displaced laterally into
      the direction of the forced bite side both during cycle series into intercuspal
      position and, although to a lesser extent, when occlusal contact was eliminated
      using flat occlusal splints. Apparently, in children with a lateral forced bite
      the neuromuscular co-ordination of the temporomandibular joint is disturbed.
      Subsequent research projects demonstrated similar findings. Consequently, a
      lateral forced bite in children should be eliminated as early as possible, in
      order to enable normal growth and development of the stomatognathic system.

PMID- 19382543
TI  - [Focal epithelial hyperplasia of the oral mucosa. A unique manifestation of human
      papillomavirus].
AB  - A 34-year old Creole woman appeared at the dermatology department with white-pink
      spots on the oral mucosa, which had been there for some time. Histology showed
      lesions characteristic of focal epithelial hyperplasia. The patient was treated
      with a CO2 laser. Focal epithelial hyperplasia is a rare benign lesion and is
      caused by human papillomavirus subtypes 13 or 32; it only appears on the oral
      mucosa.

PMID- 19382544
TI  - [Dental Health International Netherlands].
AB  - Dental Health International Netherlands is a Dutch organization, founded in 1976.
      The main goal of the organization is improving oral health care in developing
      countries, focusing on prevention and supporting local oral health care
      organizations. Dental Health International Netherlands endeavours being a
      facilitary organization for oral health care providers in low income countries as
      well as serving as a center of knowledge for dentists and dental hygienists
      willing to volunteer in deprived communities.

PMID- 19382545
TI  - DeVries wins 2009 Wiley Award.

PMID- 19382546
TI  - Responders and public health groups comment on revising sampling standard.

PMID- 19382547
TI  - AOAC stakeholders panel on veterinary drug residues comes to consensus on fitness
      for-purpose.

PMID- 19382548
TI  - Chemical contaminants and residues in food community identifies method needs,
      forms new working group, and more.

PMID- 19382549
TI  - Green tea, vitamins D and B, milk thistle, cranberries, and turmeric top list of
      ingredients ranked; call for methods issued.

PMID- 19382550
TI  - Method for aflatoxins B1, B2, G1, and G2 and ochratoxin A in ginseng and ginger
      granted Official Method status.

PMID- 19382551
TI  - Method for determination of aconitum alkaloids in dietary supplements and raw
      botanical materials granted AOAC Official Method status.

PMID- 19382552
TI  - Modification of Official Method 2003.09 and PTM 100201 approved.

PMID- 19382553
TI  - Thin-layer radiochromatography.

PMID- 19382554
TI  - Usefulness of Adams-Harbertson protein precipitation-based wine tannin method.

PMID- 19382555
TI  - Usefulness of Adams-Harbertson protein precipitation-based wine tannin method.

PMID- 19382556
TI  - Agricultural materials community priority studies and emerging feed issues.

PMID- 19382557
TI  - Determination of oxytetracycline/oxytetracycline hydrochloride in animal feed,
      fish feed, and veterinary medicinal products by liquid chromatography with
      fluorescence detection: collaborative study.
AB  - A method for determining oxytetracycline (OTC) in animal feed, fish feed, and
      veterinary medicinal products at medicated use and contamination levels was
      collaboratively studied. The method is applicable to the analysis of animal feeds
      and mineral premixes containing levels > or =2 mg/kg, and fish feed containing
      levels > or =10 mg/kg. Oxytetracycline hydrochloride (OTC.HCI) is extracted from
      ground feed material in acid-methanol solution using mechanical agitation. After
      centrifugation for 5 min at 1230 x g, an aliquot of the extract is diluted with
      water andlor acid-methanol so that the concentration of OTC.HCI is approximately
      the same as that in the working standard, and the solutions contain at least 50%
      water. Injectable veterinary medicinal materials (also called animal remedy
      materials) are diluted with water andlor extractant to reach the target
      concentration. The extracts are filtered and analyzed by reversed-phase liquid
      chromatography with fluorescence detection with excitation at 390 nm and emission
      at 512 nm. Twenty-eight test samples of medicated feeds, supplements, and drug
      premixes, including 4 test samples for trace-level analysis, were sent to 17
      collaborators in Canada, The Netherlands, and the United States. Results were
      received from 11 laboratories. The RSDr values (within-laboratory repeatability)
      ranged from 1.26 to 9.21%; RSDR values (among-laboratory reproducibility) ranged
      from 2.14 to 12.9%, and HorRat values ranged from 0.54 to 3.02. It is recommended
      that this method be adopted AOAC Official First Action.

PMID- 19382558
TI  - Multiresidue mycotoxin analysis in corn grain by column high-performance liquid
      chromatography with postcolumn photochemical and chemical derivatization: single
      laboratory validation.
AB  - A multiresidue method was developed and validated for simultaneous analysis of 5
      families of mycotoxins in corn grain. Deoxynivalenol (DON); aflatoxins B1, B2,
      G1, G2; ochratoxin A; zearalenone; and fumonisins FB1 and FB2 are extracted from
      corn grain samples with water-methanol, and extracts are cleaned up using
      immunoaffinity and solid-phase extraction columns. The column high-performance
      liquid chromatographic method uses postcolumn photochemical derivatization for
      detection of aflatoxins and derivatization with o-phthalaldehyde for detection of
      fumonisins. Mean recoveries and relative standard deviation values (%) over
      studied fortification levels for the chosen matrixes were: DON 89.9, 8.7;
      aflatoxin B1 85, 9.4; aflatoxin B2 82.4, 9.7; aflatoxin G1 74.8, 13.5; aflatoxin
      G2 79.2, 10.0; fumonisin B1 96.2, 8.0; fumonisin B2 84.5, 6.4; zearalenone 91.7,
      11.5; and ochratoxin A 87.4, 15.8. The method performance criteria, including
      specificity, accuracy, repeatability, operational range, and detection limits,
      were found to be within specifications set by the Feed Additives and Contaminants
      Group of the AOAC Agricultural Materials Community.

PMID- 19382559
TI  - Progress on the development and single-laboratory validation of a high
      performance liquid chromatographic method for the determination of carbadox and
      pyrantel tartrate in type B and C medicated feeds.
AB  - Carbadox, an antimicrobial agent, and pyrantel tartrate, an anthelmintic, are
      feed additives that are often used in combination in the United States. The
      current AOAC methods for these analytes are spectrophotometric, using standard
      addition techniques. These methods are labor-intensive and prone to variability
      as well as matrix interferences. Published methods for both analytes that use
      high-performance liquid chromatography were evaluated and a test method was
      developed. The method uses a water prewetting step to enhance extraction of
      pyrantel followed by extraction with acetonitrile-ethanol (50 + 50). Sample
      extracts are filtered through a glass fiber filter and purified using alumina
      solid-phase extraction columns. Chromatography is performed on a C18 column with
      a gradient mobile phase of dibutylamine acetate and acetonitrile. The data show
      that both analytes exhibit acceptable peak shape when a C18 column that is both
      acid- and base-deactivated is used. Linearity has been established and initial
      recovery studies on medicated swine feeds are promising.

PMID- 19382561
TI  - Determination of starch, including maltooligosaccharides, in animal feeds:
      comparison of methods and a method recommended for AOAC collaborative study.
AB  - Starch is a nutritionally important carbohydrate in feeds that is increasingly
      measured and used for formulation of animal diets. Discontinued production of the
      enzyme Rhozyme-S required for AOAC Method 920.40 invalidated this method for
      starch in animal feeds. The objective of this study was to compare methods for
      the determination of starch as potential candidates as a replacement method and
      for an AOAC collaborative study. Many starch methods are available, but they vary
      in accuracy, replicability, and ease of use. After assays were evaluated that
      differed in gelatinization method, number of reagents, and sample handling, and
      after assays with known methodological defects were excluded, 3 enzymatic
      colorimetric assays were selected for comparison. The assays all used 2-stage,
      heat-stable, a-amylase and amyloglucosidase hydrolyses, but they differed in the
      gelatinization solution (heating in water, 3-(N-morpholino) propanesulfonic acid
      buffer, or acetate buffer). The measured values included both starch and
      maltooligosaccharides. The acetate buffer-only method was performed in sealable
      vessels with dilution by weight; it gave greater starch values (2-6 percentage
      units of sample dry matter) in the analysis of feed/food substrates than did the
      other methods. This method is a viable candidate for a collaborative study.

PMID- 19382560
TI  - Single-laboratory validation for the quantification of neomycin B and neomycin C
      in animal feeds by liquid chromatography fluorescence detection with post-column
      derivatization.
AB  - A method using ion-exchange liquid chromatographic (LC) separation, post-column
      derivatization, and fluorescence detection to quantify neomycin B and neomycin C
      in animal feeds has been developed and validated. Improved methodology is
      required to achieve positive identification of antibiotics present and to more
      accurately determine the amount of antibiotics in feeds. The method sample range
      covers additive levels found in type A, B, and C medicated feed products (50
      0.005% wt/wt neomycin base). The linear range for the method covers 50-150% of
      expected sample concentrations. Average recovery from type A and B feeds, n = 9,
      was 100.4% neomycin with %RSD = 2.28. Average recovery from type C feeds and milk
      replacers, n = 9, was 97.5% neomycin with %RSD = 4.36. There were no
      interferences from soybean meal and milk replacer matrix components,
      oxytetracycline, or other aminoglycosides, with the exception of one gentamicin
      isomer, which co-elutes with neomycin B. However, neomycin and gentamicin are not
      a legal feed combination, and the presence of gentamicin can easily be discerned
      by the appearance of the 3 gentamicin homologs that do not interfere. Comparison
      of the proposed LC method to the microbiological method shows that the LC method
      provides comparable recoveries of neomycin from feed products throughout the
      range of concentrations found commercially.

PMID- 19382562
TI  - Factors affecting accuracy and time requirements of a glucose oxidase-peroxidase
      assay for determination of glucose.
AB  - Accurate and rapid assays for glucose are desirable for analysis of glucose and
      starch in food and feedstuffs. An established colorimetric glucose oxidase
      peroxidase method for glucose was modified to reduce analysis time and evaluated
      for factors that affected accuracy. Time required to perform the assay was
      reduced by approximately 40% by decreasing incubation time and removing steps
      that do not affect absorbance. Although linear regressions of absorbance and
      glucose concentrations of standard solutions exceeded R2 of 0.9997, evaluation of
      sum of squared residuals, root mean squared error, and significance of the
      quadratic term indicated that the curves were approximately quadratic in form.
      Inadequate equilibration of glucose anomers did not appear to be the issue.
      Historic data suggest that the standard curve is inherently nonlinear. Quadratic
      curves predicted standard solution glucose concentrations more accurately than
      did linear forms; overestimations at the midpoint of the curve averaged 0.04,
      0.48, and 0.92% for quadratic and linear equations calculated from 5 standard
      solutions and a linear equation calculated from the 0 and most concentrated
      standard solution, respectively. A hydrophilic antioxidant at levels no greater
      than 10 micromol ascorbic acid/0.10 g air-dried sample did not affect absorbance
      values.

PMID- 19382563
TI  - Evaluation of analytical methods for the determination of moisture, crude
      protein, crude fat, and crude fiber in distillers dried grains with solubles.
AB  - A number of analytical methods for constituents commonly measured in distillers
      dried grains (DDG) are practiced in laboratories serving the agricultural sector.
      A large interlaboratory variability among results has been observed in the
      industry. Methods for moisture, crude fat, and crude fiber are empirical, thus
      part of this variability can be attributed to the use of different methods of
      analysis. A study was organized and supported by the American Feed Industry
      Association, the Renewable Fuels Association, and the National Corn Grain
      Association to evaluate the efficacy, applicability, and the intralaboratory
      variation of a number of methods for moisture, crude protein, crude fat, and
      crude fiber in DDG with solubles (DDGS). The moisture methods included in the
      study are AOAC 930.15, AOAC 934.01, AOAC 935.29, AOAC 2003.06, and National
      Forage Testing Association (NFTA) 2.2.2.5; the crude protein methods studied are
      AOAC 990.03 and AOAC 2001.13; the crude fat methods studied are AOAC 945.16, AOAC
      954.02, AOAC 2003.05, and AOAC 2006.06; and the crude fiber methods studied are
      AOAC 978.10 and AOCS Ba 6a-05. A second study was undertaken to assess existing
      interlaboratory variation of the same methods in 23 laboratories. Based on the
      results of these studies, the sponsoring associations established recommended
      reference methods for use in commercial trade of DDGS. The reference methods
      selected are NFTA 2.2.2.5 for moisture, AOAC 990.03 and AOAC 2001.11 for crude
      protein, AOAC 945.16 for crude fat, and AOAC 978.10 for crude fiber.

PMID- 19382564
TI  - Gravimetric determination of acid detergent fiber and lignin in feed:
      interlaboratory study.
AB  - On the basis of AOAC Official Method 973.18, a collaborative study was performed
      to determine fractions of acid detergent fiber (ADF) and lignin (ADL) in animal
      feed. The study used 6 animal feed and forage samples as blind duplicates and
      involved 22 participants from 7 countries. The samples analyzed covered a range
      from 3.5 to 70% ADF and from <1 to 20% ADL. Repeatability standard deviations
      ranged from 0.27 to 0.95% for ADF and from 0.08 to 0.59% for ADL. The
      reproducibility standard deviations ranged from 0.56 to 2.44% for ADF and from
      0.52 to 2.09% for ADL. Analyzed samples comprised clover and grass silages, soy
      meal, cattle feed, wheat, and sawdust. The studied method has been published as
      the EN ISO 13906:2008 standard.

PMID- 19382565
TI  - Interlaboratory validation of the Mehlich 3 method for extraction of plant
      available phosphorus.
AB  - The Mehlich 3 (M3) method is widely used for extraction of plant-available
      phosphorus (P) from soil over a wide range of pH values. The method is also used
      by many laboratories to determine multiple plant-available nutrients
      simultaneously. However, this method has not been statistically validated within
      and among laboratories. The objective of this study was to determine the
      repeatability (within-laboratory performance) and reproducibility (among
      laboratories performance) of the M3 method by using a wide variety of soils. An
      in-house homogeneity test was conducted for 10 soils. Three replicates of each of
      the 10 soils were sent to 26 domestic and international laboratories primarily
      for P analysis. Samples were scooped, weighed, or both scooped and weighed for
      extraction. The P in extracts was quantified by the participating laboratories by
      using inductively coupled plasma-atomic emission spectrometry (ICP-AES) or
      colorimetrically. For the scooped samples analyzed colorimetrically, the
      repeatability relative standard deviation (RSDr) ranged from 2.07 to 12.1%; the
      RSDr ranged from 2.2 to 21.4% for the scooped samples analyzed by ICP-AES. For
      the weighed samples analyzed colormetrically, the RSDr values were 1.09-9.34%,
      and for the weighed samples analyzed by ICP-AES, they were 1.70-5.76%. For the
      reproducibility data, the RSDR values ranged from 6.85 to 50.8% for the scooped
      colorimetry category, from 6.95 to 73.9% for the scooped-ICP-AES category, from
      7.19 to 42.6% for the weighed-colorimetry category, and from 5.29 to 35.9% for
      the weighed-ICP-AES category. The greatest RSD values were associated with the
      Susitna soil, which had the smallest concentration of extractable P. Because of
      the relatively small concentration of P in this soil, the laboratories were
      attempting to measure solution concentrations that were close to the detection
      limits. The Horwitz ratios (HorRat) were also used to evaluate the repeatability,
      HorRat(r), and reproducibility, HorRat(R). Overall, the M3 P method appears to be
      both repeatable and reproducible across the 4 categories, and the vast majority
      of the HorRat values for both repeatability and reproducibility were within the
      acceptable range. The results of this study indicate that the M3 P method for the
      determination of plant-available P in soil is both accurate and precise when
      standardized procedures are used. The method has been shown to be suitable for
      use as a reference method for testing soil materials for extractable P.

PMID- 19382566
TI  - Extraction of aucubin from seeds of Eucommia ulmoides Oliv. using supercritical
      carbon dioxide.
AB  - Supercritical CO2 was used as solvent for the extraction of aucubin from the
      seeds of Eucommia ulmoides Oliv. The co-solvent composition was tested and
      extraction conditions were optimized. Results showed that the best co-solvent was
      a water-ethanol mixture (1 + 3, v/v), and the highest yield was obtained when the
      extraction was performed under 26 MPa at extraction and separation temperatures
      of 55 and 30 degrees C for 120 min, using 6 mL co-solvent/g material at a CO2
      flow rate of 20 L/h. In a comparison of the supercritical CO2 and Soxhlet
      extraction methods, the Soxhlet method needed 3 h to extract 10 g material,
      whereas the supercritical CO2 extraction technique needed only 2 h to extract 100
      g material, thus showing a high extraction capability. The supercritical CO2
      extraction produced a higher yield, with a lower cost for the extraction. Owing
      to the advantages of low extraction temperature, high yield, and ease of
      separating the product from the solvent, supercritical CO2 extraction is likely
      to be developed into an ideal technique for the extraction of aucubin, a compound
      with thermal instability, from the seeds of this plant.

PMID- 19382567
TI  - Determination of Aconitum alkaloids in dietary supplements and raw botanical
      materials by liquid chromatography/UV detection with confirmation by liquid
      chromatography/tandem mass spectrometry: collaborative study.
AB  - An interlaboratory study was conducted to evaluate a method for the determination
      of 3 Aconitum alkaloids, viz., aconitine, mesaconitine, and hypaconitine, in raw
      botanical material and dietary supplements. The alkaloids were extracted with
      diethyl ether in the presence of ammonia. After cleanup by solid-phase extraction
      to remove matrix interferences, the alkaloids were determined by reversed-phase
      liquid chromatography (LC)/UV detection at 235 nm with confirmation by LC/tandem
      mass spectrometry (MS/MS). A total of 14 blind duplicates were successfully
      analyzed by 12 collaborators. For repeatability, the relative standard deviation
      (RSDr) values ranged from 1.9 to 16.7%, and for reproducibility, the RSDR values
      ranged from 6.5 to 33%. The HorRat values were all <2 with only one exception at
      2.3. All collaborating laboratories had calibration curves with correlation
      coefficients of >0.998. In addition, 6 collaborators performed the confirmation
      and were able to verify the identities of the alkaloids by using LC/MS/MS.

PMID- 19382568
TI  - Column high-performance liquid chromatographic method for the simultaneous
      determination of rosiglitazone and metformin in a pharmaceutical preparation.
AB  - An efficient, sensitive, and simple method was developed for the simultaneous
      determination of rosiglitazone and metformin hydrochloride in a combination
      tablet dosage form by column high-performance liquid chromatography. The mobile
      phase used was ammonium dihydrogen phosphate adjusted to pH 5.25 with sodium
      hydroxide. The limits of detection and quantitation were in the range of 0.5-1.6
      microg/mL, respectively, for metformin hydrochloride, and 0.00201-0.0067
      microg/mL, respectively, for rosiglitazone. The linearity was studied in the
      concentration range of 0.12-0.31 microg/mL for rosiglitazone and 30.6-76.7
      microg/mL for metformin hydrochloride. The recovered amounts of metformin
      hydrochloride and rosiglitazone were 100-103.8 and 101-103.7%, respectively.

PMID- 19382569
TI  - Colorimetric determination of sildenafil citrate (Viagra) through ion-associate
      complex formation.
AB  - A simple, quick, accurate, and sensitive colorimetric method is described for the
      determination of sildenafil citrate (SLD). The method is based on the reaction of
      SLD with Congo Red, Sudan II, and Gentian Violet in buffered aqueous solutions at
      pH 2.5, 6.5, and 11.0, respectively, to give highly colored soluble ion-associate
      complex species; the colored products are quantitated colorimetrically at 523,
      554, and 569 nm, respectively. The various experimental conditions were
      optimized. The stoichiometric ratio was found to be 1:1 for all ion associates;
      the calculated logarithmic stability constants were 8.51, 7.79, and 5.58,
      respectively. Beer's law was obeyed over the concentration range of 0.2-7.0
      microg/mL, whereas the Ringbom optimum concentration range was 0.4-6.5 microg/mL.
      Values for molar absorptivity, Sandell sensitivity, and detection and
      quantification limits were also calculated. The proposed method was successfully
      applied to the determination of SLD in Viagra tablets and in serum samples by
      using the technique of standard additions with mean accuracy values of 100.06 +/-
      1.14, 99.87 +/- 0.70, and 99.86 +/- 0.97% for Viagra tablets and 99.88 +/- 0.60,
      99.90 +/- 0.90, and 100.24 +/- 0.80% for serum samples, respectively.

PMID- 19382570
TI  - Spectrophotometric determination of doxazosin mesylate in tablets by ion-pair and
      charge-transfer complexation reactions.
AB  - Two accurate, easy spectrophotometric methods for the determination of doxazosin
      mesylate were described. The first method was based on the formation of ion-pair
      complexes with the acidic sulfophthalein dyes bromocresol purple (BCP) and
      bromophenol blue (BPB) in pH 3.3 and 4.5 citrate-phosphate buffer, respectively.
      The formed complexes were extracted into dichloromethane, and their absorbance
      was measured at 403 and 410 nm for BCP and BPB, respectively. The second method
      was based on the charge transfer reaction of the drug as an n-electron donor with
      either 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or 7,7,8,8
      tetracyanoquinodimethane (TCNQ) as pi-acceptors, to give colored radical anions.
      The absorbances of products were measured at 457 nm in acetonitrile and 838 nm in
      methanol for DDQ and TCNQ, respectively. Under the optimum reaction conditions,
      Beer's law was obeyed with a good correlation coefficient (r = 0.9997-0.9999) in
      the concentration ranges 3.0-18.0, 3.0-20.0, 15.0-95.0, and 10.0-100.0 microg/mL
      for the BCP, BPB, DDQ, and TCNQ methods, respectively. Limits of detection of the
      BCP, BPB, DDQ, and TCNQ methods were 0.314, 0.408, 1.935, and 1.610 microg/mL,
      respectively. The limits of quantification were 1.045, 1.360, 6.449, and 5.367
      microg/mL, respectively. The parameters molar absorptivity, precision, accuracy,
      recovery, robustness, and stability constant were studied. The proposed methods
      were successfully applied for determination of the drug in tablets with good
      accuracy and precision. Statistical comparison of the results with those obtained
      by a reported method showed good agreement and indicated no significant
      difference in accuracy and precision.

PMID- 19382571
TI  - Column liquid chromatography-ultraviolet and column liquid chromatography/mass
      spectrometry evaluation of stress degradation behavior of escitalopram oxalate.
AB  - The objective of this work was to study the degradation behavior of escitalopram
      oxalate under different International Conference on Harmonization (ICH)
      recommended stress conditions by column liquid chromatography (LC)-UV and LC/mass
      spectrometry (LC/MS) and to establish a validated stability-indicating LC assay
      method. Escitalopram oxalate was subjected to stress conditions of hydrolysis,
      oxidation, photolysis, and thermal decomposition. Extensive degradation was found
      to occur in alkaline medium. Mild degradation was observed in acidic and
      oxidative conditions. Escitalopram oxalate was stable to neutral, photolytic, and
      thermal stress. Successful separation of the drug from degradation products
      formed under stress conditions was achieved on a PerfectSil-100 ODS-3 column [C18
      (5 microm, 25 cm x 4.6 mm id)] using methanol-0.01 M acetate buffer pH 3.8
      adjusted with acetic acid (45 + 55) as the mobile phase. The flow rate was 1
      ml/min, and the detection wavelength was 239 nm. The method was validated
      according to ICH guidelines. Major degradation products formed in hydrolysis and
      oxidative conditions were isolated, and structural elucidation of degradation
      products was done by LCIMS and infrared spectrometry studies. The major
      hydrolysis degradation product was confirmed as 1-(3-dimethylaminopropyl)-1-(4
      fluoro- phenyl)-1,3dihydroisobenzofuran-5-carboxylic acid, and the major
      oxidative degradation product was confirmed as 1-{[3-dimethylamino(oxide)-
      propyl]-1-(4-fluro-phenyl)}-1,3-dihydro-isobenzofuran- 5-carbonitrile.

PMID- 19382572
TI  - Development and validation of a column high-performance liquid chromatographic
      method for determination of sibutramine in capsules.
AB  - The development and validation of a reversed-phase liquid chromatographic (LC)
      method for the determination of sibutramine hydrochloride monohydrate in capsules
      is described. An isocratic LC analysis was performed on a reversed-phase RP-18
      column (250 x 4.6 mm id, 5 microm particle size). The mobile phase consisted of
      methanol-water-triethylamine (80 + 20 + 0.5, v/v/v), with pH adjusted to 5.65
      with 85% phosphoric acid, and was pumped at a constant flow rate of 1.0 mL/min.
      Measurements were made at a wavelength of 223 nm. The calibration curve was
      linear over the range of 15-40 microg/mL [correlation coefficient (r2) = 0.9998].
      The relative standard deviation (RSD) value for intraday precision was 0.84%. The
      RSD value for interday precision was 0.90%. Recoveries ranged from 99.64 to
      100.66%. No interferences from the excipients were observed. Because of its
      simplicity and accuracy, the method is suitable for routine quality control
      analysis of sibutramine in capsules.

PMID- 19382573
TI  - Validated column high-performance liquid chromatographic method for determination
      of aspirin and clopidogrel in combined tablets in the presence of degradation
      products formed under ICH-recommended stress conditions.
AB  - The development and validation of a column high-performance liquid
      chromatographic assay method for the determination of aspirin and clopidogrel in
      tablet formulation are described. The combination formulation was subjected to
      International Conference on Harmonization-recommended stress conditions.
      Separation of the drugs from the degradation products formed under stress
      conditions was achieved on an octasilyl (C8) column using 0.3% orthophosphoric
      acid-acetonitrile (65 + 35, v/v) mobile phase. The method was validated for
      specificity, linearity, limits of detection and quantification, precision,
      accuracy, and robustness. The method was found to be specific against placebo
      interference and during the forced degradation. The response was linear in the
      concentration range of 30.0-120.0 microg/mL for aspirin and 15.0-60.0 microg/mL
      for clopidogrel, with a correlation coefficient of 0.9999 for both. The relative
      standard deviation values for intra- and interday precision were <2.0%. The
      accuracy was between 99.12 and 99.83% for aspirin and 98.20 and 100.35% for
      clopidogrel. Stress testing showed degradation products that were well-separated
      from the parent compound, confirming the stability-indicating capacity of the
      method.

PMID- 19382575
TI  - TEMPO TVC for the enumeration of aerobic mesophilic flora in foods: collaborative
      study.
AB  - The automated system for enumeration of total viable count (TVC) in foods, TEMPO
      TVC, uses a dehydrated culture medium and an enumeration card containing 48 wells
      across 3 different dilutions for the automatic determination of the most probable
      number (MPN). The alternative method was compared in a multilaboratory
      collaborative study to AOAC Method 966.23 for determination of aerobic plate
      count for nondairy products and the Standard Methods for the Examination of Dairy
      Products (SMEDP) Standard Plate Count for dairy products. Five food types, raw
      ground beef, raw ground chicken, cooked whitefish fillets, bagged lettuce, and
      milk, were analyzed for TVC by 14 collaborating laboratories throughout the
      United States and Canada. Three lots of naturally contaminated food products
      representing a wide range of counts were tested for each of the 5 food types. The
      study demonstrated that the overall repeatability, reproducibility, and mean log
      counts of the TEMPO TVC method were statistically comparable to those of the 2
      standard methods at the 5% level.

PMID- 19382574
TI  - Estimation of pitavastatin calcium in tablet dosage forms by column liquid
      chromatography and ultraviolet spectrophotometry.
AB  - Two simple and accurate methods for the determination of pitavastatin calcium
      (PIT) in tablet dosage forms were developed and validated using column liquid
      chromatography (LC) and UV spectrophotometry. The LC separation was achieved on a
      Phenomenex Luna C18 column (250 mm, 4.6 mm id, 5 microm) in the isocratic mode
      using acetonitrile-water-triethylamine (80 + 19.8 + 0.2, v/v/v), adjusted to pH
      3.5 +/- 0.05 with orthophosphoric acid, as the mobile phase at a flow rate of 1.5
      mL/min. The retention time was 5.70 min. Both the methods were performed at 238
      nm, the wavelength of maximum absorbance of PIT in methanol. In the LC method,
      quantification was achieved with a photodiode array detector over the
      concentration range of 0.1-2.5 microg/mL with a mean recovery of 100.26 +/-
      0.75%. In the UV method, quantification was achieved over the concentration range
      of 2-20 microg/mL with mean recovery of 99.65 +/- 1.24%. Both methods were
      validated, and the results were compared statistically. They were found to be
      simple, specific, accurate, and precise. The methods were successfully applied
      for the determination of PIT in tablet dosage form without any interference from
      common excipients.

PMID- 19382577
TI  - Determination of deoxynivalenol in soft wheat by immunoaffinity column cleanup
      and LC-UV detection: interlaboratory study.
AB  - An interlaboratory study was conducted to assess the applicability of a
      previously validated method for the analysis of deoxynivalenol (DON) in cereal
      and cereal products to soft wheat in the range of >0.1-3.0 microg/g. The study
      evaluated a generic method to determine DON at levels that bracket the existing
      Canadian guidelines for DON in soft wheat destined for use in baby foods and
      nonstaple foods. Collaborators selected one of 2 approved brands of DON
      immunoaffinity column for cleanup and their choice of qualified C18 liquid
      chromatographic (LC) column. Separation was by LC with UV detection. Blind
      duplicates from 5 levels of naturally contaminated wheat and a pair of spiked
      wheat samples were successfully analyzed by 12 laboratories in 8 countries. For
      samples naturally contaminated with DON from <0.1-2.2 microg/g, the relative
      standard deviation of repeatability (RSDr) ranged from 3.1 to 14.8%. For
      reproducibility, the RSDR ranged from 21.0 to 32.9% and the HorRat range was 1.0
      to 1.9. Recoveries of 0.5 microg/g DON spiked into wheat ranged from 66 to 98%,
      with an average of 84%. The RSDr was 5.4%, the RSDR was 12.6%, and the HorRat
      value was 0.7.

PMID- 19382576
TI  - Identification of cervidae DNA in feedstuff using a real-time polymerase chain
      reaction method with the new fluorescence intercalating dye EvaGreen.
AB  - A real-time qualitative and quantitative polymerase chain reaction method (cer
      194) using the fluorescence dye EvaGreen and aimed at the cytochrome b sequence
      was established for detection of cervidae DNA in feedstuff. Eight meat meal
      samples derived from deer, bovine, ovine, camel, pig, rabbit, fish, and chicken
      and 17 cervidae hair samples covering 2 subfamilies, 4 genera, and 7 species were
      tested to prove the specificity of the cer-194 system and its universality within
      the cervidae family. Detection limit of 0.1% deer meat in fish meal, blood
      powder, and feather powder matrixes was confirmed.

PMID- 19382578
TI  - Refinement and extension of AOAC Method 2005.06 to include additional toxins in
      mussels: single-laboratory validation.
AB  - A single-laboratory validation study was undertaken for the analysis of paralytic
      shellfish poisoning (PSP) toxins in common mussels, extending AOAC Official
      Method 2005.06 to include the additional toxins dcNEO and dcGTX2,3. The method
      was refined to improve toxin oxidation product stability, analytical sensitivity
      of N-hydroxylated toxins, and throughput. Validation was performed to
      characterize the method for selectivity, sensitivity, linearity, precision,
      repeatability, recovery, ruggedness, and uncertainty. Parallel testing of
      naturally contaminated mussels enabled comparison of sample toxicities obtained
      using mouse bioassay (MBA) and high-performance liquid chromatographic (HPLC)
      methodologies. Performance characteristics of the method are reported for all
      commercially available certified reference toxins. Results from the MBA and HPLC
      methods were well correlated, and the analytical method has been instigated as
      the sole monitoring tool for UK official control surveillance of PSP toxins in
      common mussels.

PMID- 19382579
TI  - Determination of nine intense sweeteners in foodstuffs by high-performance liquid
      chromatography and evaporative light-scattering detection: interlaboratory study.
AB  - An interlaboratory trial was conducted to validate an analytical method based on
      high-performance liquid chromatographic analysis with evaporative light
      scattering detection for the simultaneous determination of 9 intense sweeteners,
      i.e., acesulfame-K, alitame, aspartame, cyclamic acid, dulcin, neotame,
      neohesperidine dihydrochalcone, saccharin, and sucralose in carbonated and
      noncarbonated soft drinks and canned or bottled fruits. Seven laboratories
      participated in the validation study. The majority of the samples fortified with
      levels close to the limit of quantification had relative standard deviation for
      reproducibility (RSDR) values <15%. In most cases, the recovery rates ranged
      between 90 and 105%, demonstrating satisfactory performance of the method. For
      samples fortified at levels comparable to the prescribed legal limits stipulated
      in the current European Union legislation, the method produces acceptably
      accurate, repeatable, and reproducible results. Trueness, expressed in terms of
      recovery rates, was demonstrated in most cases by values ranging from 90 to 108%.
      Comparability of results obtained by individual testing laboratories was good
      (RSDR values <10%) for the majority of results. Moreover, HorRat values of <1.1
      suggested good performance of the method for all sweeteners and matrixes tested.

PMID- 19382580
TI  - Evaluation of modified PCR quantitation of genetically modified maize and soybean
      using reference molecules: interlaboratory study.
AB  - Real-time polymerase chain reaction (PCR)-based quantitative methods were
      previously developed and validated for genetically modified (GM) maize or soy. In
      this study, the quantification step of the validated methods was modified, and an
      interlaboratory study was conducted. The modification included the introduction
      of the PCR system SSIIb 3 instead of SSIIb 1 for the detection of the taxon
      specific sequence of maize, as well as the adoption of colE1 as a carrier
      included in a reference plasmid solution as a replacement for salmon testis. The
      interlaboratory study was conducted with the ABI PRISM 7700 and consisted of 2
      separate stages: (1) the measurement of conversion factor (Cf) value, which is
      the ratio of recombinant DNA (r-DNA) sequence to taxon-specific sequence in each
      genuine GM seed, and (2) the quantification of blind samples. Additionally, Cf
      values of other instruments, such as the ABI PRISM 7900 and the ABI PRISM 7000,
      were measured in a multilaboratory trial. After outlier laboratories were
      eliminated, the repeatability and reproducibility for 5.0% samples were <15.8 and
      20.6%, respectively. The quantitation limits of these methods were 0.5% for Bt11,
      T25, and MON810, and 0.1% for GA21, Event176, and RR soy. The quantitation
      limits, trueness, and precision of the current modified methods were equivalent
      to those of the previous methods. Therefore, it was concluded that the modified
      methods would be a suitable replacement for the validated methods.

PMID- 19382582
TI  - Development of a carbon paste electrode containing benzo-15-crown-5 for trace
      determination of the uranyl ion by using a voltammetric technique.
AB  - The interaction of macrocyclic compounds like crown ethers and UO2(2+) has been
      studied by electrochemical methods. A modified carbon paste electrode
      incorporating benzo-15-crown-5 (B15C5) was used to evaluate the electron transfer
      reaction of UO2(2+) by cyclic voltammetry, differential pulse voltammetry, and
      electrochemical impedance spectroscopy. Electrochemical impedance studies showed
      that charge transfer resistance was less for the B15C5-modified electrode than
      for the plain carbon paste electrode (PCPE). On the basis of these observations,
      a UO2(2+)-sensitive crown ether chemically modified electrode (CME) for trace
      analysis was fabricated and investigated in aqueous solutions. It was found that
      a 5% B15C5-CME for UO2(2+) showed a better voltammetric response than did the
      PCPE. UO2(2+) could be quantified at sub-microg/mL levels by differential pulse
      voltammetry with a detection limit of 0.03 microg/mL. By differential pulse
      adsorptive stripping voltammetry, UO2(2+) could be quantified in the working
      range of 0.002-0.2 microg/mL, with a detection limit of 1.1 microg/L.
      Simultaneous determination of UO2(2+), Pb(2+), and Cd(2+) was possible. The
      method was successfully applied to the determination of UO2(2+) in synthetic, as
      well as real, samples; the results were found to be comparable to those obtained
      by inductively coupled plasma-atomic emission spectroscopy.

PMID- 19382581
TI  - Detection of parvalbumin, a common fish allergen gene in food, by real-time
      polymerase chain reaction.
AB  - Fish, as one of the most common causes of IgE-mediated food hypersensitivity, has
      recently received increasing attention from the food industry and legislative and
      regulatory agencies. A real-time polymerase chain reaction assay based on TaqMan
      MGB probe technology was developed for the detection of parvalbumin, a major fish
      allergen gene. The assay had a sensitivity up to 5 pg purified fish DNA and had
      no cross-reaction with other species, such as cattle, sheep, swine, chicken,
      shrimp, lobster, crab, squid, clam, rice, soybean, maize, and potato. The
      coefficient of variation for both intra- and interexperimental variability
      demonstrated high reproducibility and accuracy. The assay proved to be a
      potential tool for the detection and label management of fish allergens in food.

PMID- 19382583
TI  - Utilization of picolinaldehyde-4-phenyl-3-thiosemicarbazone in sodium
      dodecylsulfate micelles for the spectrophotometric determination of iron,
      vanadium, and cobalt following partial least-squares regression analysis.
AB  - Partial least-squares regression was applied for the simultaneous determination
      of iron, vanadium, and cobalt after complexation with picolinaldehyde-4-phenyl-3
      thiosemicarbazone (PAPT) in the presence of anionic sodium dodecylsulfate (SDS)
      micelles. These 3 complexed metal ions exhibited overlapping spectra in the 390
      510 nm region with a maximum absorbance at 415 nm at pH 3.0 and enhanced
      absorbance in the presence of SDS. The data for the simultaneous determination of
      these metal ions were analyzed using a simple partial least-squares (SIMPLS)
      algorithm. Formation constants (log Kf) were found to be 4.65, 3.29, and 4.85 for
      PAPT complexes of Fe, V, and Co, respectively, and the detection limits for Fe,
      V, and Co were 0.013, 0.002, and 0.010 microg/mL, respectively. Common anions and
      cations did not interfere with the proposed method. The method was validated by
      calculating root mean square error of cross-validation, root mean square error of
      calibration, and root mean square error of prediction and was applied to
      determine these 3 metal ions in real crude oil samples.

PMID- 19382584
TI  - A novel method for speciation of chromium: coprecipitation without carrier
      element by using a triazole derivative.
AB  - A coprecipitation method has been established for speciation of chromium(III) and
      chromium(VI) in real samples. The procedure is based on the coprecipitation of
      Cr(III), by using a new organic coprecipitant, 3-phenyl-4-o-hydroxybenzyl
      idenamino-4,5-dihydro-1,2,4-triazole-5-one, without adding any carrier element.
      After reduction of Cr(VI) by concentrated H2SO4 and ethanol, the method was
      applied to the determination of total Cr. The level of Cr(VI) was calculated by
      the difference of total Cr and Cr(III) levels. For optimum recovery of Cr(III),
      different analytical factors such as pH, amount of coprecipitant, centrifugation
      rate and time, and effect of sample volume, were investigated. The influences of
      some anions, cations, and transition metals on the recoveries were also
      investigated, and no significant interferences were observed. The
      preconcentration factor was 100. The detection limit based on 3 times standard
      deviation (sigma) of the blank (n = 10) for Cr(III) was 0.50 microg/L. In order
      to evaluate the accuracy of the method, certified reference materials (CRM-TMDW
      500 Drinking Water and National Institute of Standards and Technology Standard
      Reference Material 1573a Tomato Leaves) were analyzed, and the results obtained
      were in good agreement with certified values. The presented procedure was applied
      for Cr speciation in various solid and liquid samples with successful results.

PMID- 19382585
TI  - Determination of low-level acrylamide in drinking water by liquid
      chromatography/tandem mass spectrometry.
AB  - A simple and sensitive liquid chromatographic-tandem mass spectrometric
      (LC/MS/MS) method has been developed and validated to confirm and quantify
      acrylamide monomer (AA) in drinking water using [13C3] acrylamide as internal
      standard (IS). After a preconcentration by solid-phase extraction with spherical
      activated carbon, analytes were chromatographed on IonPac ICE-AS1 column (9 x 250
      mm) under isocratic conditions using acetonitrile-water-0.1 M formic acid (43 +
      52 + 5, v/v/v) as the mobile phase. Analysis was achieved using a triple
      quadrupole mass analyzer equipped with a turbo ion spray interface. For
      confirmation and quantification of the analytes, MS data acquisition was
      performed in the multireaction monitoring mode, selecting 2 precursor ion to
      product ion transitions for both AA and IS. The method was validated for
      linearity, sensitivity, accuracy, precision, extraction efficiency, and matrix
      effect. Linearity in tap water was observed over the concentration range 0.1-2.0
      microg/L. Limits of detection and quantification were 0.02 and 0.1 microg/L,
      respectively. Interday and intraday assays were performed across 3 validation
      levels (0.1, 0.5, and 1.5 microg/L). Accuracy (as mean recovery) ranged from 89.3
      to 96.2% with relative standard deviation <7.98%. Performance characteristics of
      this LC/MS/MS method make it suitable for regulatory confirmatory analysis of AA
      in drinking water in compliance with European Union and U.S. Environmental
      Protection Agency standards.

PMID- 19382586
TI  - Proficiency test for chemical laboratories for the analysis of a pesticide in a
      formulated product: interlaboratory study.
AB  - A multilaboratory proficiency testing program was conducted by the National
      Accreditation Board for Testing and Calibration Laboratories (India) and
      coordinated by the Institute of Pesticide Formulation Technology. This program
      was conducted to compare the performance of individual laboratories in the area
      of pesticide formulation (Chlorpyrifos 20 EC) analysis. A total of 24
      laboratories in India participated. Analysis of 2 parameters (i.e., estimation of
      the active ingredient and the acidity) of 2 samples of Chlorpyrifos 20 EC was the
      objective of this program. Homogeneity tests were performed before sample
      distribution. Performance of the participating laboratories was evaluated by
      using new robust statistics given in the guidelines of the National Association
      of Testing Authorities, Australia. Results were collated and statistically
      computed to calculate the value of 2 types of Z-scores (Zwi and Zbi). In addition
      to the statistical analysis, a graphical representation such as the Youden plot
      was also generated to evaluate the performance of participating laboratories.

PMID- 19382587
TI  - Determination of 142 pesticides in fruit- and vegetable-based infant foods by
      liquid chromatography/electrospray ionization-tandem mass spectrometry and
      estimation of measurement uncertainty.
AB  - A liquid chromatographic/electrospray ionization-tandem mass spectrometric method
      was developed and validated to determine 142 pesticides in fruit- and vegetable
      based infant foods, including apples, apples and bananas, pears, bananas, apple
      juice, peas, sweet potatoes, creamed corn, squash, and carrots. Pesticides were
      extracted from infant foods by using the procedure known as the quick, easy,
      cheap, effective, rugged, and safe (QuEChERS) method. Quantification was based on
      matrix-matched standard calibration curves with the use of an isotopically
      labeled standard or a chemical analogue as the internal standard to obtain method
      accuracy. The method performance parameters, including overall recovery,
      intermediate precision, and measurement uncertainty, were evaluated on the basis
      of a nested design. The performance results were calculated by using a compiled
      SAS program that provided a semiautomated procedure for handling a large number
      of calculations in a few seconds. In general, the overall recoveries, for spiking
      levels of 10, 50, and 80 microg/kg, fell in a range of 81-110%, intermediate
      precisions were <20%, and measurement uncertainties were <40%. Chlorimuron-ethyl,
      ethofenprox, haloxyfop, naptalam, primisulfuron-methyl, pyridalyl, pyridate,
      quizalofop, and tebufenozide were the method problematic pesticides that had
      large measurement uncertainty (>40%) due to low recovery andlor poor
      repeatability. The method provided an analytical range of 1-100 microg/kg with
      the lowest concentration level at 1 microg/kg for all pesticides (signal-to-noise
      ratio of >10), except for aclonifen at 5 microg/kg.

PMID- 19382588
TI  - Determination of 7B3 residues in cotton plants by liquid chromatography/mass
      spectrometry.
AB  - A method was developed for the determination of 7B3 (12-propyloxyimino-1,15
      pentadecanlactam), a novel macrolactam fungicide, by liquid chromatography/mass
      spectrometry (LC/MS) with positive electrospray ionization (ESI+). The method
      used a reversed-phase C18 column and acetonitrile-water (60 + 40, v/v) mobile
      phase. The quick, easy, cheap, effective, rugged, and safe method was used for
      extraction of 7B3 from cotton plants, which involved the extraction of 10 g
      homogenized sample with 10 mL acetonitrile, followed by the addition of 4 g
      anhydrous MgSO4 and 1.0 g NaCl. After centrifugation, 1 mL of the buffered
      acetonitrile extract was transferred into a tube containing 50 mg primary
      secondary amine sorbent and 100 mg anhydrous MgSO4. After shaking and
      centrifugation, the final extract was transferred to an autosampler vial for
      concurrent analysis by LC/MS. The results of 7B3 determined by LC/MS in the
      selective ion monitoring mode were linear, and the matrix effect of the method
      was evaluated. The average recoveries of 7B3 fortified at different levels were
      within 84.1-100.2%, and the relative standard deviations were <7.5% for all
      samples analyzed. The method limit of detection and the limit of quantitation
      values were 0.03 and 0.1 mg/kg, respectively. The proposed method was
      successfully applied to determine 7B3 residues in practical samples. This method
      is sensitive, accurate, reliable, simple, and safe.

PMID- 19382589
TI  - Development of a partial least-squares calibration model for simultaneous
      determination of elements by inductively coupled plasma-atomic emission
      spectrometry.
AB  - A partial least-squares (PLS) calibration model was developed for simultaneous
      multicomponent elemental analysis with inductively coupled plasma-atomic emission
      spectrometry (ICP-AES) in the presence of spectral interference. The best
      calibration model was obtained using a PLS2 algorithm. Validation was performed
      with an artificial test set. Multivariate calibration models were constructed
      using 2 series of synthetic mixtures (Zn, Cu, Fe, and U, V). Accuracy of the
      method was evaluated with unknown synthetic and real samples.

PMID- 19382590
TI  - Conclusions on measurement uncertainty in microbiology.
AB  - Since its first issue in 1999, testing laboratories wishing to comply with all
      the requirements of ISO/IEC 17025 have been collecting data for estimating
      uncertainty of measurement for quantitative determinations. In the
      microbiological field of testing, some debate has arisen as to whether
      uncertainty needs to be estimated for each method performed in the laboratory for
      each type of sample matrix tested. Queries also arise concerning the estimation
      of uncertainty when plate/membrane filter colony counts are below recommended
      method counting range limits. A selection of water samples (with low to high
      contamination) was tested in replicate with the associated uncertainty of
      measurement being estimated from the analytical results obtained. The analyses
      performed on the water samples included total coliforms, fecal coliforms, fecal
      streptococci by membrane filtration, and heterotrophic plate counts by the pour
      plate technique. For those samples where plate/membrane filter colony counts were
      > or =20, uncertainty estimates at a 95% confidence level were very similar for
      the methods, being estimated as 0.13, 0.14, 0.14, and 0.12, respectively. For
      those samples where plate/membrane filter colony counts were <20, estimated
      uncertainty values for each sample showed close agreement with published
      confidence limits established using a Poisson distribution approach.

PMID- 19382591
TI  - Analytical determination of virginiamycin drug residues in edible porcine tissues
      by LC-MS with confirmation by LC-MS/MS.
AB  - A liquid chromatographic-mass spectrometric (LC-MS) method was developed and
      validated for the determination and confirmation of virginiamycin (VMY) M1
      residues in porcine liver, kidney, and muscle tissues at concentrations > or =2
      ng/g. Porcine liver, kidney, or muscle tissue is homogenized with methanol
      acetonitrile. After centrifugation, the supernatant is diluted with phosphate
      buffer and cleaned up on a C18 solid-phase extraction cartridge. VMY in the
      eluate is partitioned into chloroform and the aqueous upper layer is removed by
      aspiration. After evaporating the chloroform in the residual mixture to dryness,
      the dried extract is reconstituted in mobile phase and VMY is quantified by LC
      MS. Any samples eliciting quantifiable levels of VMY M1 (i.e., at concentrations
      > or =2 ng/g) are subjected to confirmatory analysis by LC-MSIMS. VMY S1, a minor
      component of the VMY complex, is monitored but not quantified or confirmed.

PMID- 19382592
TI  - Assay of florfenicol in swine feed: interlaboratory study.
AB  - Nuflor (florfenicol) Premix for Swine was recently approved by the U.S. Food and
      Drug Administration (FDA) for control of swine respiratory disease (SRD). A
      simple method for the assay of florfenicol in Type C medicated swine feeds was
      recently evaluated as part of a 4-laboratory study. Florfenicol is extracted from
      ground feed with acetonitrile-water by shaking and sonication. An Envi-Carb solid
      phase extraction cartridge is used to clean up the extract, retaining matrix
      interferences while allowing florfenicol to elute. The collected eluent is
      diluted and injected into a reversed-phase liquid chromatographic system. Samples
      are quantitated by external standard analysis versus multilevel calibration
      solutions. The procedure is suitable for the quantification of swine feeds in
      mash or pellet form medicated with 100-300 mg/kg florfenicol. The interlaboratory
      study was conducted according to Guidance 136 issued by the FDA Center for
      Veterinary Medicine. The feeds used to evaluate method performance represented
      different feed compositions (starter and finisher) and manufacturers. The sponsor
      and 3 independent laboratories obtained mean recoveries (+/-SD) from fortified
      swine feeds of 100.7% (+/-2.0%), 99.6% (+/-2.8%), 98.8% (+/-1.4%), and 99.3% (+/
      1.7%), respectively. Excellent agreement of the results of the assay of blind
      samples of commercial swine mash and pelleted feeds between laboratories
      demonstrates that the method is rugged and reproducible.

PMID- 19382593
TI  - Determination of macrocyclic lactone drug residues in animal muscle by liquid
      chromatography/tandem mass spectrometry.
AB  - A robust, credible, and practical multiresidue method based on liquid
      chromatography/tandem/mass spectrometry (LC/MS/MS) was developed for the
      simultaneous determination of 9 macrocyclic lactone drugs (abamectin B1a,
      doramectin, erythromycin, ivermectin B1a, josamycin, kitasamycin, roxithromycin,
      tilmicosin, and tylosin A) in bovine, porcine, chicken, and sheep muscles. The
      drugs were extracted with acetonitrile, and the extracts were defatted with n
      hexane and further cleaned up on a C18 solid-phase extraction cartridge. LC/MS/MS
      data acquisition was achieved by using the multiple-reaction monitoring (MRM)
      mode, i.e., 2 transitions, to provide a high degree of sensitivity and
      repeatability. Matrix-matched standard calibration curves were used to achieve
      the best accuracy of the method by compensating for the matrix effect. The
      calibration graphs were linear (r > 0.998) from 10 to 1000 ng/mL for
      erythromycin, josamycin, kitasamycin, roxithromycin, tilmicosin, and tylosin, and
      from 5 to 250 ng/mL for abamectin, doramectin, and ivermectin. The average
      recoveries of the 9 drugs were between 64.5 and 105%, calculated by using matrix
      matched calibration, with relative standard deviation values ranging from 1.6 to
      14%. The limits of detection were 0.1 microg/kg for erythromycin, josamycin,
      roxithromycin, and tylosin; 0.2 microg/kg for tilmicosin and kitasamycin; and 0.5
      microg/kg for abamectin, doramectin, and ivermectin. For confirmation, the MRM
      ratios for the 9 drug residues in the samples and the solvent were evaluated and
      found to be within the ratio criteria set by the guidelines of the European
      Union.

PMID- 19382594
TI  - Determination of 17alpha-ethynylestradiol, carbamazepine, diazepam, simvastatin,
      and oxybenzone in fish livers.
AB  - A method using liquid chromatography/tandem mass spectrometry (LC/MS/MS) was
      developed for the determination of 17alpha-ethynylestradiol in fish liver; a
      second method using LC/MS was developed for the determination of carbamazepine,
      diazepam, simvastatin, and oxybenzone in fish liver. The fish liver samples were
      extracted and cleaned up by using liquid-liquid extraction and solid-phase
      extraction before the extracts were analyzed by LC/MS or LC/MS/MS with
      electrospray negative and positive ionization. Recoveries of the 5 target
      compounds from spiked catfish liver ranged from 72 +/- 2 to 100 +/- 3%. Limits of
      quantification for the 5 compounds were between 4.2 and 12.3 ng/g (wet weight).
      Ten turbot (Pleuronichthys verticalis) liver samples were analyzed; levels of
      17alpha-ethynylestradiol, carbamazepine, simvastatin, and oxybenzone were below
      the detection limits. Diazepam was detected in all 10 fish liver samples at
      concentrations ranging from 23 to 110 ng/g (wet weight).

PMID- 19382595
TI  - [Treatment of non small cell lung cancer].
AB  - According to the recent data lung cancer in Czech republic is the most common
      malignancy in men (incidence 93/100 000) and is the leading cause of cancer death
      in men (mortality 90/100 000). In women is the incidence of lung cancer 30/100
      000. Non-small-cell lung cancer (NSCLC) accounts for 70% to 75% of all lung
      cancers, while small-cell lung cancer (SCLC) accounts for 25% to 30% of cases.
      These two types of lung cance have a different biological characteristics which
      leads to a different approach in the treatment of NSCLC and SCLC. The treatment
      of NSCLC is based on clinical stage of disease and different treatment modalities
      alone or in combination are used: surgery, radiotherapy, chemotherapy and
      recently a novel treatment strategy--targeted therapy with biologic agents.

PMID- 19382596
TI  - [Possibilities of resistance prediction to neoadjuvant concomitant
      chemoradiotherapy in the treatment algorithm of patients with rectal carcinoma].
AB  - BACKGROUNDS: Neoadjuvant concomitant chemoradiotherapy has become a standard
      treatment of locally advanced rectal adenocarcinomas (LARA). It leads to
      shrinkage of the tumor mass and subsequently to an increase in complete
      resections (R0 resections), increasing a feasibility of sphincter-sparing
      intervention avoiding colostomy. It is based on concurrent application of
      fluoropyrimidines (5-fluorouracil, capecitabine) and radiotherapy (45 - 50,4 Gy).
      It shows less acute toxicity and improves local control rate in comparison to
      adjuvant treatment. Unfortunately, neoadjuvant chemoradiotherapy is not
      beneficial for all patients. The treatment response ranges from a complete
      pathological remission (pCR, ypT0ypN0) to a resistance. It is reported that cca
      15 percent of patients with advanced rectal cancer show pCR which is indicative
      of improved long-term prognosis. DESIGN: The following is a review of the
      significance of neoadjuvant concomitant chemoradiotherapy in the treatment
      algorithm of patients with LARA and summary of potentional clinical-pathological
      and molecular markers of response prediction to neoadjuvant therapy. The most
      important clinical studies concern serum tumor markers levels, clinical lymph
      node classification. The components of the carcinogenic pathways are explored,
      including oncogenes, tumor supressor genes, microsatellite instability (MSI) and
      potentional markers involved in apoptosis, angiogionesis, proliferation as well
      as metastasis and invasion, are reviewed. Finally, the role of specific enzymes
      associated with the metabolism of fluoropyrimidines are examined. CONCLUSIONS: No
      one marker has been consistently identified as clinically applicable. Studies
      designed to determine the potentional markers are hampered by various techniques
      as well as tumor heterogenity and recent scientific approach--studying individual
      molecular markers. Gene expression profiling analysis of multiple genes from the
      same tumor is becoming reality. We suppose that this assessment will lead in
      future in finding combination of markers for predicting prognosis and response to
      therapy in rectal cancer.

PMID- 19382597
TI  - [Epidermal growth factor receptor and radiotherapy].
AB  - Epidermal growth factor receptor (EGFR) plays an important role in cell-cycle
      regulation, proliferation, differentiation, and surviving of epithelial tissues.
      Aberrant overexpression of EGFR can initiate uncontrolled cell proliferation with
      subsequent formation of epithelial carcinomas. Correlation between EGFR
      overexpression and increased resistance of tumor tissues to ionizing radiation
      has been described by many authors. Strategy of tumor radiosensitization by EGFR
      inhibition seems to have a great potential in the treatment of epithelial
      cancers. Rationale for EGFR inhibition in combination with ionizing radiaton
      arises from published results of many radiobiological studies, which describe the
      role of EGFR in cytoprotective and pro-proliferative reactions of human tumor
      cells, induced by irradiation. These reactions result in accelerated tumor
      repopulation, which is subsequently counter-productive to the effect of
      radiotherapy. Presented article is an overview of EGFR and its function in
      healthy and tumor tissues; likewise, it describes the relation of EGFR to
      ionizing radiation; therapeutic approaches to EGFR function modulation in
      combination with radiotherapy in preclinical and clinical use.

PMID- 19382599
TI  - [The role of National Institute of Hygiene in historical perspective].
AB  - The article presents the role of the National Institute of Hygiene, during the 90
      years of its presence, in the struggle for heath of the population. It underlines
      how the scope of action of the Institute was contiunuously adjusted in response
      to existing health treats and how the Institute contributed to detection of new
      risk factors. The main tasks of the Institute included prevention of disease and
      implementation of the most up-to-date developments in the country public health
      system.

PMID- 19382598
TI  - [A retrospective analysis of trastuzumab-based therapy in metastatic breast
      cancer patients at Masaryk Memorial Cancer Institute. Identification of
      predictive factors].
AB  - INTRODUCTION: Trastuzumab is a humanized monoclonal antibody directed against the
      HER-2 receptor. Trastuzumab-based therapy significantly improves response rate
      (RR), time to progression (TTP) and overall survival (OS) for women with HER-2
      positive metastatic breast cancer. Despite its initial efficacy, acquired
      resistance to trastuzumab develops in a majority of patients with MBC, and a
      large subset never responds, demonstrating primary resistance. The purpose of
      this retrospective study was to determine prognostic factors applicable to
      clinical practice. METHODS: We enrolled 112 women with metastatic breast cancer,
      who started the trastuzumab-based therapy at Masaryk Memorial Cancer Institute
      until January 2007. Clinical and laboratory factors, such as: patients
      conditions, character ofmetastatic spread, histology, estrogen, progesterone and
      Her-2 receptor status, Her-2/neu gene amplification, and serum tumor markers CEA,
      CA 15-3 and extracellular domain of Her-2 receptor (S-HER-2 ECD) were monitored.
      The association of all factors to response to therapy, time to progression (TTP)
      and overall survival (OS) was assessed. RESULTS: In 95% patients, the trastuzumab
      was combined with cytostatics (83% taxanes), 88,4% of patients started the
      trastuzumab as the first or second-line anticancer treatment. The median TTP was
      284 days (9,3 months) and the median OS was 612 days (20,1 months) for all
      patients, RR was 54,5%. The highest RR was associated with the first-line
      treatment (p<0.0001) and with HER-2 gene/Chromosome 17 ratio > 2,2 (p=0,0092).
      Eleven patients (9,8%) discontinued the treatment because of toxicity, 7 patients
      did it as a result of cardiotoxicity (6,2%). CNS metastases occurred in 31
      patients (27,7%). The S-HER-2 ECD was the most frequently elevated serum marker
      at the time of the treatment initialization (72,5%) and at the time of the
      progression (55,9%). Cox regression analysis identified S-HER-2 ECD levels at the
      beginning and between day 90 and 130 of the trastuzumab therapy as the best
      predictors of TTP. On the other hand the best predictor of OS was level of CEA
      before the treatment started and level of S-HER-2 ECD between day 90 and 130 of
      the trastuzumab therapy. CONCLUSIONS: We confirmed that the only one predictive
      marker for response to trastuzumab therapy is a proof of HER-2 tumor
      positivity.The highest prevalence of S-HER-2 ECD positivity among serum tumor
      markers and the strong association between initial and subsequent S-HER-2 ECD
      serum concentrations and time to progression and overall survival make the S-HER
      2 ECD the most significant prognostic marker.

PMID- 19382600
TI  - [Evaluation of usefulness of commercial recomwell Campylobacter enzyme--linked
      immunosorbent assays for routine serodiagnosis of Campylobacter jejuni and
      Campylobacter coli infections].
AB  - The commercially available enzyme-linked immunosorbent assays (ELISA recomWell
      Campylobacter) from Mikrogen was evaluated for the diagnosis of Campylobacter
      jejuni and Campylobacter coli infections. Serum samples from 20 healthy controls,
      44 persons with symptoms of primary Campylobacter infection and 24 serum samples
      from patients with Yersinia enterocolitica or Salmonella infections were tested.
      This ELISA assay detects IgA and IgG antibodies against three recombinant
      antigens of the Campylobacter jejuni and Campylobacter coli: OMP 18 (18 kDa),
      PEB4 (31 kDa) and P39 (39 kDa). The healthy controls showed significantly lower
      antibody titers in all two immunoglobulin classes. The IgA antibodies were
      diagnosed only in 2 (18.2%) serum samples obtained from patients with
      bacteriologically confirmed campylobacteriosis. The presence of IgG antibodies
      was confirmed in 82% of serum samples. Furthermore, we showed that 66.7% of the
      33 serum samples obtained from the patients suspected for campylobacteriosis not
      confirmed by isolation, were positive for IgG and 15.2% for IgA antibodies. We
      observed also not specific reactions in ELISA recom Well Campylobacter with sera
      obtained form patients with yersiniosis and salmonelosis. This study demonstrates
      the usefulness of commercially available assay for the routine diagnosis of
      Campylobacter infection but with some limitations.

PMID- 19382601
TI  - [Influence of sub-mics of selected antibiotics on hydrophobic and adhering
      properties of Klebsiella pneumoniae strains isolated from urine samples].
AB  - The aim of this study was to evaluate the effects of sub-MICs of selected
      antinbiotics on hydrophobic and adhering properties of Klebsiella pneumoniae
      rods. Cefotaxime, gentamicin, ciprofloxacin and tetracycyline were used. The
      hydrophobicity was evaluated according to the method of Rosenberg et al. The
      adhering properties were estimated by method of Christensen et al. The exposure
      of K. pneumoniae strains to subMICs of antibiotics reduced hydrophobicity and
      adhesion to polystyrene. All antibiotics used at 1/2 MICs significantly reduced
      the hydrophobicity and adhesion to polystyrene of K. pneumoniae strains.

PMID- 19382602
TI  - [Bactericidal action of human serum against Pseudomonas aeruginosa strains with
      hydrophilic or hydrophobic cell surface].
AB  - Pseudomonas aeruginosa strains are the prominent nosocomial pathogens, especially
      dangerous for patients hospitalized in intensive care units. The cell surface
      hydrophobicity of P. aeruginosa rods and resistance to the bactericidal action of
      serum are considered as important factors of their virulence. The aim of the
      study was to evaluate the susceptibility of hydrophilic and hydrophobic P
      aeruginosa strains to the bactericidal effect of human serum. These strains were
      isolated from bronchioloalveolar lavage of children with hospital-acquired
      pneumonia. The BATH test was used to evaluate the hydrophobic properties. Among
      tested P aeruginosa strains seven had strong hydrophobic properties and eight
      strains were hydrophilic. The data showed that hydrophobic strains were more
      frequently serum-resistant than rods with hydrophilic cell surface.

PMID- 19382603
TI  - [The analyze of capability of biofilm synthesis by Staphylococcus aureus strains
      isolated from children with cystic fibrosis].
AB  - The aim of this study was to analyse the capability of biofilm synthesis by S.
      aureus isolates obtained from the respiratory tract of CF (cystic fibrosis)
      patients. A total of 297 S. aureus strains isolated from 33 CF patients, and 40
      isolates obtained from healthy control children, were analysed. Extracellular
      slime production was determined using phenotypical methods (Congo red agar, and
      crystal violet) and molecular techniques (icaA and icaD genes amplification). All
      S. aureus strains possessed the icaA and icaD genes belonging to the operon
      responsible for slime synthesis. The isolates obtained from the respiratory tract
      of CS patients more frequently showed the ability to produce a biofilm than those
      from healthy individuals.

PMID- 19382604
TI  - [The frequency of small colony variants of Staphylococcus aureus strains isolated
      from children with cystic fibrosis].
AB  - The aim of this study was to determine the frequency of spontaneous and inducible
      SCV formation in S. aureus isolates obtained from CF patients. A total of 297 S.
      aureus strains isolated from 33 CF patients, and 40 isolates obtained from
      healthy control children, were analysed. S. aureus was cultured on Columbia blood
      agar, Schaedler agar and Chapman agar under aerophilic and microaerophilic
      conditions. Subinhibitory gentamicin concentrations (1 mg/L) were used to test S.
      aureus ability to form SCVs. The study showed that the characteristic feature of
      S. aureus strains, persistently colonizing the airways of CS patients, was the
      formation of small colony variants. In the subinhibitory gentamicin
      concentration, S. aureus strains from CS patients formed SCVs more frequently
      (55%) than isolates from healthy subjects (20%). SCV formation in CF patients was
      associated with treatment with inhaled aminoglycosides.

PMID- 19382605
TI  - [Validation of nested RT-PCR method for detection of measles virus in clinical
      samples].
AB  - The aim of this study was to perform the validation of nested RT-PCR method for
      detection of measles virus genome in laboratory of Virology Department (NIZP-PZH)
      conditions. The PCR reactions were made with specific primers for nucleoprotein
      gene. The validation of nested RT-PCR assay includes determination of limit of
      detection (LOD), specificity, intra- and inter-assay precision and influence of
      materials from clinical samples on the PCR reaction. The detection limit of
      nested RT-PCR was 255-510 RNA MeV/ml. The obtained results reveal high precision
      and lack of substances present in clinical samples influence on the PCR reaction.
      The application of nested RT-PCR assay for viral genomes other than MeV gave
      negative results. The obtained results indicated that the nested RT-PCR fulfilled
      validation criteria and can be used for routine laboratory diagnostics of measles
      virus.

PMID- 19382606
TI  - [Memory of professor Ireneusz Roszkowski, pionier of Polish gynecology and
      obstetrics - 100th birthday].

PMID- 19382607
TI  - Effects of presacral neurectomy on pelvic pain in women with and without
      endometriosis.
AB  - OBJECTIVE: Presacral neurectomy (PSN) is used in treatment of central chronic
      pelvic pain (CPP); however, the confounding effect of concomitant resection of
      endometriosis remains uncertain. This study was undertaken to evaluate and
      compare the effectiveness of presacral neurectomy (PSN) in the presence and
      absence of endometriosis. MATERIAL AND METHODS: Twenty-three women with midline
      CPP (age 30.3 +/- 7.9, range 21-46) unresponsive to medical therapy were
      recruited to the study. Endometriosis was absent in seven and present in sixteen
      subjects. Laparoscopic PSN using a harmonic scalpel was performed in all
      subjects; simultaneous excision of endometriotic lesions was also carried out in
      subjects with endometriosis. Intensity of dysmenorrhoea and pelvic pain was
      measured by visual analogue pain scale (VAPS) at 3 and 12 months postoperatively.
      RESULTS: Dysmenorrhoea decreased at 3 months by 75% (P = 0.018) in those without
      endometriosis and by 78% (P = 0.001) in those with endometriosis. At 12-months,
      dysmenorrhea increased in women with endometriosis (P = 0.008), but not in those
      without endometriosis. Pelvic pain not related to menses decreased by 67% (P = 
      0.0007) and by 87% (P = 0.028), respectively, in women with and without
      endometriosis. Dyspareunia, declined dramatically at 3 and 12 months to a median
      score of 0 (the majority of subjects had no discomfort; P < 0.001); the change in
      dyspareunia between 3 and 12 months was in favour of patients without
      endometriosis (P = 0.02) CONCLUSIONS: PSN using a harmonic scalpel results in
      long-term pain relief, especially in patients without endometriosis.

PMID- 19382608
TI  - Hemodynamic parameters following bilateral internal iliac arteries ligation as a
      treatment of intrapartum hemorrhage.
AB  - OBJECTIVE: The internal iliac arteries ligation (IIAL) is a particularly
      effective method, maintaining fertility, of dealing with intrapartum hemorrhage.
      AIM: Hemodynamic evaluation of the ovarian arteries(OA) and uterine arteries (UA)
      in patients after IIAL. MATERIAL: Study Group consisted of 6 women who underwent
      IIAL to treat intrapartum hemorrhage--without hysterectomy. Control Group
      consisted of 6 women, at the same age group, parity and time after delivery, who
      did not undergo IIAL. METHOD: Perfusion characteristics were studied by means of
      a transvaginal Doppler system. Resistance index (RI), pulsatility index (PI) and
      systolic/diastolic ratio (S/D) were measured in the uterine and ovarian arteries.
      Nonparametric comparison of the two groups was performed with the help of Two
      sample Wilcoxon rank-sum (Mann-Whitney) test. RESULTS 1. Change of perfusion in
      OA-PI: 1.40 vs. 3.76 Prob < 0.05; RI: 0.86 vs. 0.91 Prob > 0.05; S/D: 3.25 vs.
      18.2 Prob < 0.05. 2. Change of perfusion in UA-PI: 2.20 vs. 2.75 Prob > 0.05; RI
      0.82 vs. 0.86 Prob > 0.05; SID: 5.28 vs. 7.81 Prob > 0.05. CONCLUSIONS: 1. IIAL
      as a way of treating intrapartum haemorrhage, causes the decrease of pulsatility
      index (PI) and systolic/diastolic ratio (S/D) in ovarian arteries. 2.
      Characteristic changes of PI, RI and S/D parameters in uterine arteries after
      IIAL have not been observed. 3. Changes of ovarian flow velocity parameters
      suggest the possibility of changes in the ovarian function.

PMID- 19382609
TI  - [Presentation of our own results of twin-to-twin laser therapy].
AB  - OBJECTIVE: To present our own results of selective laser photocoagulation of
      communicating vessels in twin-to-twin transfusion syndrome. MATERIAL AND METHODS:
      From April 2005 till January 2008 in the Department of Obstetrics in Gdansk, 37
      selective laser photocoagulation of communicating vessels were performed on 38
      patients with twin-to-twin transfusion syndrome. Surgery--delivery interval and
      data about neonates were collected and analyzed. At least one survival, two
      survivals and overall survival rate were calculated. RESULTS: At least one baby
      survived in 84% of patients, two babies--in 62% women. Overall survival rate was
      73%. CONCLUSIONS: Results of the treatment were similar to other centers and
      fully encourage laser surgery instead of earlier used amnioreductions wherever it
      is possible.

PMID- 19382610
TI  - [Evaluation of the embryonic and foetal heart rate at 6(+0) to 11(+6) weeks of
      gestation].
AB  - OBJECTIVE: To establish the normal range of embryonic heart rate (EHR) and foetal
      heart rate (FHR) at 6(+0) to 11(+6) weeks of gestation, to evaluate the risk of
      pregnancy loss depending on EHR and FHR values and to establish if checking of
      FHR with the use of M-mode method is possible in different levels obstetric
      departments. MATERIAL AND METHODS: Transvaginal or transabdominal ultrasound
      using M-mode in 255 singleton pregnancies. Maternal age varied between 16 and 44
      years (mean 29 +/- 5 years). There were 67% primigravidas. Gestational week was
      established on the basis of CRL measurements. Demographic factors, obstetrical
      history and follow-up were collected. Data was statistically reviewed. RESULTS:
      FHR varied between 47 and 192 bpm (mean 154 +/- 26 bpm). At 6 weeks, mean EHR was
      116 +/- 21 bpm, then slowly increased, reaching mean 172 +/- 9 bpm at 10 weeks.
      At 11 weeks the mean FHR achieved the level of 165 +/- 7 bpm. The difference was
      statistically significant. The r-correlation ratio between FHR and the
      gestational week was 0.58. In case of 7 embryos (2.75%) at 6.1 to 8.1 weeks of
      gestation slow FHR was noted (< 100 bpm). The scan performed 7-10 days later
      revealed miscarriages in all cases. CONCLUSIONS: EHR and FHR in the first
      trimester depends on gestational week. It increases since 6 to 9 weeks and
      decreases after 10 weeks. The highest values of FHR are observed between 9 and 10
      weeks of gestation. The risk of early pregnancy loss increases significantly in
      case of detecting slow FHR. FHR can be checked by M-mode methods using any kind
      of ultrasound machine.

PMID- 19382611
TI  - [Prognostic value of chosen parameters of mechanical and bioelectrical uterine
      activity in prediction of threatening preterm labour].
AB  - OBJECTIVES: To record and analyse bioelectrical activity of the uterine muscle in
      the course of physiological pregnancy, labour and threatening premature labour;
      to define which parameters from the analysis of both electrohysterogram and
      mechanical activity signal allow us to predict threatening premature labour.
      MATERIAL AND METHODS: Material comprised 62 pregnant women: Group I--27 patients
      in their first physiological pregnancy, Group II--21 patients in their first
      pregnancy with symptoms of threatening premature labour, and Group III--14
      patients in the first labour period. The on-line analysis of the mechanical
      (TOCO) and electrical (EHG) contraction activity relied on determination of
      quantitative parameters of detected uterine contractions. RESULTS: The obtained
      statistical results demonstrated a possibility to differentiate between Group I
      and II through the amplitude and contraction area for EHG signal, and only the
      contraction amplitude for TOCO signal. Additionally, significant differentiating
      parameters for electrohysterogram are: contraction power and its median
      frequency. Analyzing Group I and III, significant differences were noted for
      contraction amplitude and area obtained both from EHG and TOCO signals.
      Similarly, the contraction power (from EHG) enables us to assign the contractions
      either to records from Group I or to labour type. There was no significant
      difference noted between Group II and III. CONCLUSIONS: Identification of
      pregnant women at risk of premature labour should lead to their inclusion in
      rigorous perinatal surveillance. This requires novel, more sensitive methods that
      are able to detect early symptoms of the uterine contraction activity increase.
      Electrohysterography provides complete information on principles of bioelectrical
      uterine activity. Quantitative parameters of EHG analysis enable the detection of
      records (contractions) with the symptoms of premature uterine contraction
      activity.

PMID- 19382612
TI  - [Ways of coping in stressful situations and anxiety-state or anxiety-trait among
      women with symptoms of perinatal depression].
AB  - OBJECTIVES: The aim of the following study was to establish whether there is any
      connection between an elevation of anxiety experienced by women during pregnancy
      or postpartum and their styles of coping with stressful situations, as well as to
      assess if those factors influence higher risk of incidence of perinatal
      depressive symptoms. MATERIAL AND METHODS: A total of 229 patients admitted to
      the Department of Foeto-Maternal Medicine, Pomeranian Medical University,
      Szczecin in 2006-2007, were recruited for the study. By means of the Edinburgh
      Postnatal Depression Scale (EPDS), a study group of 76 pregnant and postpartum
      women with high risk of perinatal depression was assigned, as well as a control
      group of 153 patients without such risk. The level of anxiety and ways of coping
      in stressful situations were measured by means of the CISS (Coping Inventory for
      Stressful Situations) and STAI (State-Trait Anxiety Inventory) questionnaires.
      RESULTS: It has been shown that specific styles of coping in stressful situations
      and Anxiety-state or Anxiety-trait have substantial influence on higher risk of
      perinatal depressive symptoms in women. CONCLUSIONS: 1) The risk of perinatal
      depressive symptoms is associated with ways of coping with stressful situations
      or Anxiety-state and Anxiety-trait, 2) the risk of perinatal depression among
      pregnant women increases with an elevation of emotion-concentrated styles of
      coping in stressful situations, 3) the risk of perinatal depression among
      postpartum women increases with an elevation of emotion-concentrated ways of
      coping in stressful situations and engagement in substitute activities, 4)
      analysis of undertaken research indicate for suitableness of early diagnosis of
      specific styles of coping in stressful situations in order to implement proper
      therapy directed at the reduction of the risk of perinatal depression.

PMID- 19382613
TI  - [Occurrence of fungal infections in pregnant women and non-pregnant women with
      diabetes and without diabetes].
AB  - Diabetes and pregnancy are thought to be independent factors increasing the risk
      of fungal infections. OBJECTIVES: The aim of the study was to evaluate the
      occurrence of fungal infection of the vagina, rectum and oral cavity in pregnant
      and non-pregnant women with and without diabetes. MATERIAL AND METHODS: 627 women
      were included in the study, among them healthy non-pregnant women (HN), healthy
      pregnant women (HP), pregnant women with diabetes (PD) and non-pregnant women
      with diabetes (ND). In total, 1881 samples obtained from the vagina, rectum and
      oral cavity were tested. For species identification API 20 C i API C AUX tests
      were used. RESULTS: Fungi in at least one locus were detected in 62.4% of all
      women, among them in 69.8% of HN, 58.5% of HP, 62.5% of PD and 62.7% of ND.
      Strains were isolated from vaginal samples of HP (16%) less often than in HN
      (27%) (95% CI 0.29-0.85; OR = 0.5); in ND (31%) and PD (25%) there were no
      differences in the occurrence of fungi in the vagina (95% CI 0.37-1.38; OR =
      0.71). Similar rates of prevalence of fungi in rectum were found in HN (30%) and
      HP (23%) (95% CI 0.43-1.16; OR = 0.7) as well as in ND (27%) and PD (24%) (95% CI
      0.41-1.64; OR = 0.82). Strains have been isolated from oral cavity of 57% of HN
      and 54% of HP (95% CI 0.58-1.42; OR = 0.9) as well as from 55% ND and 59% of PD
      (95% CI 0.65-2.21; OR = 1.2). CONCLUSIONS: Lower prevalence of fungi in the
      vagina of HP, in comparison to HN, suggests a protective effect of pregnancy on
      the risk of vaginal mycosis. Pregnancy and diabetes independently have no
      influence on the prevalence of fungi in oral cavity and rectum.

PMID- 19382614
TI  - [Selective estrogen receptor modulators in treatment of postmenopausal
      osteoporosis].
AB  - Postmenopausal osteoporosis is associated with lack of estrogens, therefore,
      understandably one of the treatment options in osteoporosis is a group of
      medicines known as selective estrogen receptor modulators (SERMs). They can act
      as an estrogen receptor agonist in some tissues, whereas as an antagonist in
      others. In relation to this antago-antagonistic action, SERMs have a positive
      effect on bones, the serum lipid profile and the cardio-vascular system.
      Moreover, they can protect against some estrogen-dependent neoplasm development.
      The first used SERM was tamoxifen, but due to its negative effect on endometrium
      it is not indicated in osteoporosis. Raloxifen, which is currently in use,
      besides the reduction of vertebral fractures risk, has beneficial influence on
      endometrial and breast neoplasm development risk as well. On the other hand,
      raloxifen intensifies vasomotor symptoms and its bone-protecting effect is
      limited. At present, new SERMs (ospemifen, lasofoxifen, bazedoxifen, arzoxifen)
      are being researched in clinical trials. In the current stage of investigations
      they reveal beneficial influence on skeletal as well as extraskeletal tissues.
      Implementation of SERMs in combined therapy of osteoporosis is currently under
      research as well. SERM with parathormone or SERM with bisphosphonate might prove
      to be an advantageous treatment option for women with severe or resistant
      osteoporosis. An addition of SERM to conventional hormonal replacement therapy
      did not bring the anticipated benefits. Future studies on SERMs may result in new
      preparations adjusted to individual needs of the patients.

PMID- 19382615
TI  - [Recommendation of The Polish Gynecological Society about medical exams and
      treatment of adolescent females].

PMID- 19382616
TI  - [Central Coordinating Center Summary of the National Cervical Cancer Screening
      Program in Poland in the period from January 1st till December 31st 2008].

PMID- 19382617
TI  - [Allergy and vaccination].
AB  - The article presents evidence on postvaccinal reactions to vaccinal antigens
      (VA), admixtures and additives. VA complications are also specified. Causes of
      postvaccinal reactions including allergy are analysed with a focus on Grippol
      vaccine used in 2006-2007.

PMID- 19382618
TI  - [Myofibrillar protein tropomyosin and allergic cross-reactivity].
AB  - Myofibrillar protein tropomyosin (TM) is a normal physiological protein
      participating in regulation of muscular contraction. It is widely prevalent among
      living organisms. This explains cross-reactivity of allergic patients to home
      dust, sea fish, cockroaches, etc. The presence of similar IgE-binding epitopes in
      TM of different origin is a key factor in development of cross-reactivity (CR).
      CR to TM is a general biological phenomenon. We consider modified TM as a basic
      component in design of allergovaccines of a new generation.

PMID- 19382619
TI  - [IgE-autoantibodies in patients with atopic dermatitis].
AB  - Atopic dermatitis (AD) is a complicated and multifactorial disease. Autoimmune
      reactions to own antigens (Ag) revealed in AD patients can aggravate a clinical
      course of this disease. The aim of the study was to identify IgE antibodies (IgE
      Abs) to tissue Ags in AD patients and to evaluate a relationship between the
      levels of these IgE-Abs and the level of the total IgE. Serum samples from 75 AD
      patients and 24 healthy persons of different age were examined with enzyme
      immunoassay for IgE-Abs to 7 tissue Ags (keratin, collagen of type III and VI,
      elastin, myosin, myelin basic protein - MBP, thyroglobulin), total IgE and IgE
      Abs to exoallergens. The levels of IgE-Abs to all investigated tissue Ags (except
      for MBP) were higher (p < 0.05) in AD patients than in healthy persons. Incidence
      rate of IgE-Abs to various tissue Ags varied widely (39-78%) and did not depend
      upon age. Significant correlations were found between the levels of IgE-Abs to
      collagen of type VI (r = 0.32), thyroglobulin (r = 0.78) and of total IgE.
      Therefore, most of stimulating IgE-autoreactivity Ags are involved in the
      pathologic process in AD, keratin, collagen of type IV, thyroglobulin being more
      important. This may aggravate an AD course.

PMID- 19382620
TI  - [Activation processes in the lymphocytes of patients with latent sensitization].
AB  - Latent sensitization is a risk factor of a clinically manifest atopic reaction.
      Investigation of a phenotypic composition of lymphocytes reveals function of the
      immune system in this condition. Indirect fluorescence assessed differential and
      activation lymphocyte antigens (CD4, CD3, CD8, CD16, CD20 and CD25, CD71, HLA-DR,
      CD95, CD23, CD54, respectively) in 15 patients with latent sensitization, 32
      patients with atopic bronchial asthma and 22 healthy donors. The immune system
      demonstrated definite activation with involvement ofT- and B-links of the immune
      system. Lymphocyte activation in latent sensitization and bronchial asthma
      differs by high expression of CD95 apoptosis trigger receptor. Enhancement of Fas
      mediated lymphocyte apoptosis may inhibit IgE synthesis and atopic pathology
      manifestation.

PMID- 19382621
TI  - [Metabolic aspects in pathogenesis of burn endotoxicosis].

PMID- 19382622
TI  - [Effects of systemic administration of glutamate antibodies on acute convulsive
      reaction of C57B1/6 mice].
AB  - The impact of a single intraperitoneal injection of antibodies to glutamate (AG)
      on acute generalized epileptic activity provoked by systemic introduction of
      pentilentetrasol was studied in C57B1/6 mice. It was found that AG in doses 10,
      25 and 50 mg/kg 1.5 and 24 hours after AG injection produced an anti-epileptic
      action by raising thresholds of clonic convultions and tonic phase of convultions
      with lethal outcome and by extending a latent period of their appearance. Later
      (30 hours after antibodies introduction in a dose 25 mg/kg) AG had no effects on
      the convulsive reaction thresholds, 48 hours after AG injection they produced a
      proepileptic effect by lowering the threshold of a clonic convulsion phase.

PMID- 19382624
TI  - [The role of lymphocyte-platelet adhesions, cytokines and endothelial dysfunction
      in pathogenesis of cold-induced lesions].
AB  - We studied the role of lymphocyte-platelet adhesion, IL-1beta, TNFalpha and
      endothelial dysfunction in pathogenesis of damage in local frostbites.
      Examination of 60 patients aged 17-50 years with frostbites of the second-forth
      degree has demonstrated that in patients with local frostbites the number of
      lymphocyte-platelet adhesions, circulating desquamated endothelial cells
      increases as well as the level of proinflammatory cytokines, while nitrites
      concentration decreases.

PMID- 19382623
TI  - [Characteristics of the morphofunctional condition of cell populations by the
      modal cell class in response to transplantation of lymphocytic leukemia p-388].
AB  - On the model of transplanted leukemia p-388, cytophotometry has shown that
      tumors' impact on the body includes two stages: direct affection of the target
      organ, indirect affection through changes in functional relations with cell
      populations of other organs due to the impact of transformed cells of the damaged
      target organ. Moreover, the progress of tumor growth alters functional relations
      between the organs.

PMID- 19382625
TI  - [Some hints about the reviewers' ethical dilemmas].
AB  - Some prevalent, important ethical issues concerning the manuscript reviewing
      process are discussed, with special reference to the referees' irresponsibility,
      bias, conflict of interest, conflict of opinion, clash between rapidity of
      publication and careful revision, and anonymity, suggesting possible amendments.

PMID- 19382626
TI  - [Key ethic discussions in hospice/palliative care].
AB  - The goal of palliative care is to provide the best possible quality of life for
      patients and their families in the process of dying as well as before, during the
      course of illness. Emphasis is on the role of team approach in every aspect of
      patient care. The moral principles of sacredness of life and the right of
      personal autonomy may occasionally come in conflict. The basic principle of the
      respect of life prohibits killing, which has been accepted in one way or another
      by all societies - for the reasons of survival. Similar to this, modern morality
      supports the principle of respecting autonomy and self-management based on
      informed, conscious personality of an individual. Still, if the needs of another
      person appear to be more important or desirable than reaching certain individual
      goals, then the right of an individual regarding autonomy may be legitimately
      limited. Decisions on not applying or terminating certain procedures must be
      based on thorough discussion and consideration of the nature and expected result
      of treatment. If the patient is not competent, then the discussion should involve
      a team providing care for the patient and a representative of the patient. When
      the physician and the team can clearly see that unfavorable effects of treatment
      will outweigh therapeutic benefits, then, according to medical ethics of the
      respecting beneficiary, the team is not obliged to provide that form of
      treatment. Except for palliative care, there is no medical treatment that is
      always obligatory. A physician that does not accept the patient's request to be
      killed does not limit the patient's autonomy. Autonomy is self-management and
      capability of the patient to kill him/herself is not limited by the physician's
      refusal to do so. Even in those cases when patients for various reasons say that
      death will be a relief, it does not mean that the physician is obliged to
      terminate life. The superior obligation of physicians is to alleviate pain. If
      euthanasia would be legal, it would discourage those that work in the field of
      medical education and search for new ways to diminish pain. The progress in the
      development of palliative care would be stopped worldwide. Supporting the belief
      that killing is forbidden could increase the benefits for the society, whereas
      forbidding the concept of "allowing to die" despite the use of all-powerful
      technologies does not seem to maximize beneficial effects. In fact, if the latter
      be valid, then all patients at intensive care units with all the possible life
      sustaining facilities would have to die. Yet, members of the unit health care
      team would be accused of a deed considered equivalent to murder. For autonomy to
      be accomplished, competence is required, and that is something that varies,
      passing through different stages. In medical context, a person is competent when
      he/she is able to understand the basic information about the illness, including
      prognosis, if she/he is able to understand the treatment suggested, differentiate
      between the risk and benefit, and come to a rational decision. A partially
      competent person can, if he/she wants and is able to, reach joint decisions with
      the rest of the team. If the person is not competent and has not delegated a
      proxy (representative) and has not provided written instructions for the future,
      the health care team does not know what the patient would want if competent. Then
      the team handles according to the principles of doing good and no harm. The role
      of the "directive for the future" and proxy-decision-makers becomes problematic
      for the following reasons. By the time when the directives should be implemented
      many forms of medical treatment have been further developed, so that the illness
      may have become curable or treatment easier. Older and weak people that need care
      and feel they pose a burden could feel forced to sign directives for the future
      if they are legally obligatory.

PMID- 19382627
TI  - [Metric analysis of temporomandibular joint in asymptomatic persons by magnetic
      resonance imaging].
AB  - AIM: The objective of this study was to investigate the prevalence of anterior
      disk displacement and condyle position in volunteers free from clinical symptoms
      and signs of temporomandibular disorders. MATERIAL AND METHODS: Bilateral
      parasagittal T1-weighted magnetic resonance images of temporomandibular joints
      (TMJ) in 25 asymptomatic volunteers (age range 21-27, mean 23.4 years; 18 (72%)
      female and 7 (28%) male) were analyzed and metric measurements of disk and
      condyle position were investigated. Metric analysis of the position and
      relationship between the disk and the condyles were described using Kurita et al.
      method of measuring relative and absolute distances of reference points. On
      statistical data analysis, the left and right TMJs of each person were presented
      as two separate entities. The methods of nonparametric statistics were used.
      RESULTS: Anterior disk displacement was found in 5 (20%) asymptomatic volunteers
      (four of them female). Anterior displacement with unilateral reduction and
      anterior displacement without reduction unilaterally was present in two subjects
      each, whereas one volunteer had anterior displacement without reduction
      bilaterally. There was no difference in the calculated position of condyle
      between joints with and without disk displacement (Kruskal-Wallis test, p <
      0.05). DISCUSSION: This study evaluated the prevalence of asymptomatic anterior
      disk displacement in symptom-free healthy volunteers and the condyle position in
      the glenoid fossa. Displaced disk is the main cause of temporomandibular pain;
      however, studies in asymptomatic volunteers also suggest it to be an anatomic
      variant. The relationship between dorsocranially positioned condyle and
      anteriorly displaced temporomandibular joint disk is a controversial issue.
      Metric analyses were only made in parasagittal plane. CONCLUSION: There was
      difference in the calculated disk position between joints with and without disk
      displacement, but this study found no difference in the calculated condyle
      positions according to the presence or absence of disk displacement.

PMID- 19382628
TI  - [Renal impairment induced by nonselective prostaglandin inhibitor].
AB  - The role of kidney function is of utmost importance in the maintenance of
      constant body fluid amount. However, kidneys are at a great risk of exposure due
      to high intrarenal blood flow and the existing concentrate system. Different
      damage can originate from renal clearance of various drugs, while metabolites or
      xenobiotics may be associated with potential nephrotoxic effects, particularly in
      the presence of additional risk factors. For analgesics such as nonsteroidal
      antirheumatics (NSARs), it is possible that they inhibit renal production of
      prostaglandins, potent vasodilators, resulting in tissue ischemia and direct
      toxicity. Therefore, the aim of this study was to evaluate changes in the
      cellular potential response of proximal tubules first in the presence of
      prostaglandin type E (PGE2) and then in the presence of Na-diclofenac, a
      nonselective prostaglandin inhibitor, and their effects on transport process of
      substrate (glucose), by using electrophysiological studies in experimental
      animals. PGE2 was found to play specific role at local intrarenal level, where
      they directly stimulated the processes of sodium and substrate (glucose)
      cotransport through luminal membrane of proximal tubules, without changing the
      control cell potential response. Results with diclofenac as a nonselective
      cyclooxygenase inhibitor and thus prostaglandin synthesis inhibitor revealed it
      to cause concentration-dependent depolarization of the cellular potential. It
      also reduces cotransport of the substrates and ions involved in intracellular
      equilibrium. At concentrations higher than therapeutic, diclofenac became
      nonspecific and therefore caused permanent depolarization. Accordingly, the
      results of these experimental studies may be useful to specialists treating
      patients suffering from renal dysfunction or kidney diseases. This can also
      contribute to rationalization of the therapeutic use of analgesics, greater
      caution and better recognition of the associated risk factors, in elderly or
      renal patients in particular.

PMID- 19382629
TI  - [Beliefs of Croatian surgeons and internists on hyperbaric oxygenation--a
      preliminary report].
AB  - BACKGROUND/INTRODUCTION: Hyperbaric oxygenation (HBO) has been accepted in many
      countries as a method of treatment in selected indications, but in Croatia it is
      still perceived with skepticism. OBJECTIVE: To determine beliefs, knowledge, and
      possible experience of Croatian surgeons and internists with HBO. SUBJECTS AND
      METHODS: An anonymous questionnaire was applied to test surgeons (N=56; 45%) and
      internists (N=68; 55%), employed in general hospitals in Zadar, Sibenik, Split,
      and Dubrovnik, Republic of Croatia. We believed that the subjects had been
      previously exposed to information campaigns about HBO and its clinical
      applications, and should have been informed about the method at a level enabling
      correct establishment of indications and routine usage of HBO in clinical
      practice. RESULTS: The majority of study subjects (N=66; 53%) had very little or
      no information at all about HBO and half of them (N=50; 40%) had no experience in
      its application. Almost all (N=123; 99%) subjects considered the method valuable
      in the treatment of decompression sickness, 56 subjects (45%) considered the
      method efficient in carbon monoxide poisoning, 31 (25%) in cerebral arterial gas
      embolism, 87 (70%) in problem wounds, and 70 (56%) in gas gangrene. The only
      statistically significant difference between the two groups of subjects was
      recorded in case of cerebral arterial gas embolism (chi2 = 7.26, P = 0.007),
      which was recognized as an indication for HBO by more internists (N=23) than
      surgeons (N=8). DISCUSSION: Insufficient understanding of HBO amongst Croatian
      surgeons and internists is probably the consequence of several factors, of which
      most important probably are insufficient curricula of undergraduate studies and
      residencies, as well as administrative obstacles. A small number of responders
      and polled hospitals necessarily resulted in a significant bias, so additional
      studies are necessary to shed more light on the issue.

PMID- 19382630
TI  - [Bioethical and legal aspects of patient education].
AB  - In the last 35 years, patient education has started to gradually develop at
      hospitals as well as in primary health care. Now, it is an integral part of
      communication in health care. Due to the expanding application of technology in
      the field of medicine, it is difficult to achieve appropriate and extensive
      patient education. Patient dissatisfaction with the given information on the
      illness, treatment and prognosis has contributed to professionalization of
      patient education. Nevertheless, patient education has not yet been acknowledged
      as a discipline. Patient education by health care professionals while providing
      health care services and through the process of informed consent requires
      professional and bioethical education of health care professionals and also
      patient commitment to actively cooperate with their doctors.

PMID- 19382631
TI  - [Plant food allergy: apple as a model].
AB  - Allergic reactions to plant foodstuffs comprise a whole spectrum of clinical
      manifestations, from very mild ones, localized to oral mucosa, to the most severe
      including life-threatening anaphylactic shock. The reason is the presence of a
      few structurally and functionally different allergens in each foodstuff. On the
      other hand, the similarity between particular allergens in different foodstuffs
      and the presence of their homologues in other sources (pollens, insect venoms)
      give a lot of possibilities for cross-reactions during allergic sensitization.
      Apple has a significant place in human nutrition. However, it is also a fruit
      that most frequently causes allergic reactions. Apple allergens are well known
      and appropriately characterized, and their homologues are present in other
      vegetable foodstuffs. Thus, apple represents a good model of plant food
      hypersensitivity. The aim of this paper is to review the mechanisms of allergic
      sensitization, the types of clinical manifestations, the influence of allergen
      content variability, and the diagnostic and therapeutic issues connected with
      plant food allergy, using apple as a model.

PMID- 19382632
TI  - [Has femoral neck fracture in older patients to be treated with reposition of
      fragments and osteosynthesis or with primary aloarthroplasty?].
AB  - In this article we analised and compared the efficiency of operative treatment of
      the femoral neck fracture in two groups of patients, over 70 years of age,
      treated on different way. The first group were the patients treated by
      osteosynthesis of the fracture site, and the second group were the patients
      treated by aloarthroplasty of the hip. All patients had surgery over three days
      after injury. We found that the group of patients with osteosynthesis had twice
      bigger unsuccessful results (62.5%) in relation to the group treated with hip
      aloarthroplasty (31.8%). The relation between the number of reoperations after
      osteosynthesis and hip aloarthroplasty was 8:1. We also found that radiological
      healing ot the fracture site after osteosynthesis happened only in 10% cases.
      Patients treated with hip aloarthroplasty earlier started to walk without help
      (1.9 months after surgery) and the patients treated with osteosynthesis could
      walk five times later (10.59 months after surgery). Although neck femoral
      fractures in older patients are treated ten times more with hip aloarthroplasty
      than with osteosynthesis, int his article we showed that hip aloarthroplasty must
      be the first choice in mostly all patients over 70 years of age. Osteosynthesis
      has to be used very rare, in patients with lateral neck fractures without
      dislocations, and it must be done as emergency procedure, not later then 48 hours
      of injury.

PMID- 19382633
TI  - [Sensitivity and specificity of clinical assessment in the diagnosis of acute
      brain diseases].
AB  - Acute brain diseases require timely and correct diagnosis. The basic guideline in
      treating these patients is clinical-neurological assessment. We tested the
      sensitivity and specificity of clinical assessment of acute brain disease
      according to definitive diagnosis determined by neuroradiology and computerized
      tomography (CT). We found a statistically significant correlation between the
      disease assessment and brain CT in patients with ischemic stroke. In patients
      with hemorrhagic stroke and brain tumors, the clinical-neurological assessment
      was found to be of statistically significantly lower sensitivity and specificity.
      Clinical assessment may produce false-positive and false-negative findings
      concerning hemorrhagic stroke and brain tumors. Study results indicated brain CT
      to be an unavoidable diagnostic method, along with clinical assessment of acute
      brain disorders.

PMID- 19382634
TI  - [Necrotizing soft tissue infection of upper extremity complicated with toxic
      shock syndrome--clinical presentation and treatment options].
AB  - Necrotizing soft tissue infections (NSTI) are uncommon infections associated with
      considerable morbidity and mortality (20%-40%). They are characterized by rapidly
      progressive necrosis of soft tissue that primarily involves subcutaneous fat and
      fascia with variable involvement of the overlying skin and muscle. Extensive soft
      tissue necrosis is often accompanied by systemic toxicity. Establishing the
      diagnosis in the early stage of the infection can be difficult, which leads to a
      delay in surgical treatment and a poor outcome. The principles of treatment are
      early and aggressive surgical debridement, broad spectrum antimicrobial therapy
      administered empirically and reassessed pending culture and sensitivity results,
      and intensive care management. We report a case of NSTI of the arm in a 64-year
      old female patient caused by group A Streptococcus and Staphylococcus aureus
      complicated with toxic shock-like syndrome with emphasis on the pathophysiology
      of toxic shock-like syndrome and treatment modalities. NSTI developed 10 days
      after a knife cut wound of the thumb. The patient had no significant comorbidity.
      Treatment included aggressive surgical debridement with removal of necrotic
      tissue and extensive fasciotomies 24 h of admission, cardiovascular stabilization
      and monitoring at intensive care unit, and repeat surgical debridement at 72 h of
      admission. Early triple drug antimicrobial therapy included high-dose
      clindamycin, which inhibits protein synthesis and bacterial exotoxin production
      that is responsible for inflammatory response and toxic shock-like syndrome. In
      addition, the patient received hyperbaric oxygen therapy (8 treatments in total).
      The above management led to control of the infective process. Prolonged surgical
      wound care followed by thin split-skin grafting and placement of secondary
      sutures on day 36 of admission preserved the extremity with good functional and
      cosmetic result.

PMID- 19382636
TI  - [Patients with tuberculosis: motivation for treatment].

PMID- 19382635
TI  - [Clinical characteristics at onset of first febrile convulsions].
AB  - AIM: The aim of this retrospective study was to establish clinical
      characteristics of first febrile convulsions in children admitted to Department
      of Pediatrics in Tuzla, Bosnia and Herzegovina, and diagnosed with febrile
      convulsions in the period from January 1, 1999 till December 31, 2004. METHODS:
      Data were collected from medical records of the children admitted to Department
      of Pediatrics in Tuzla during the study period. The study included 716 medical
      records of children aged from one month to 7 years, analyzed for the following
      data: type of seizure (simple or complex), clinical manifestation of the
      convulsion (tonic-clonic, tonic, atonic, partial unilateral), body temperature
      after convulsion, and the length of convulsion. Of laboratory tests, the findings
      indicating possible infection and electroencephalogram (EEG) results were
      analyzed. Study subjects were divided into four age groups: 1-12 months
      (infants), 13 months to 2.9 years (young), 3 to 4.9 years (middle) and 5-7 years
      (older) groups. The chi2-test and Kruskal-Wallis test were used on testing
      statistical significance of between-group differences. The level of statistical
      significance was set at p < 0.05. RESULTS: Simple febrile convulsions were found
      in 88.8% and complex febrile convulsions in 11.2% of children (p = 0.0016). Tonic
      clonic seizures were recorded in 90% and atonic in 8.6% of cases (p < 0.0001).
      Body temperature immediately after febrile convulsions ranged between 38 degrees
      C and 41.5 degrees C. Kruskal-Wallis test produced no statistically significant
      difference between the groups tested. Febrile convulsions lasted up to 5 minutes
      in 73.5% of cases, with the highest recorded in younger group (76.7%); 17.3% of
      children had seizures lasting between 6 and 10 minutes, mostly in older group
      (39%). Normal EEG findings were recorded in 96.9%, specifically altered findings
      in 1.4% and non-specifically altered findings in 1.7% of patients. DISCUSSION:
      The significantly higher prevalence of simple febrile convulsions as compared
      with complex forms and tonic-clonic seizure as the most common clinical
      manifestation of the attacks, recorded in the present study, were also confirmed
      in previous retrospective and prospective studies. It occurs with elevated body
      temperature above 38 degrees C. In the greatest proportion of children, it lasted
      for up to 15 minutes, and most children with febrile convulsions had normal EEG
      findings. CONCLUSION: Data on the clinical characteristics of first febrile
      convulsions in the Tuzla Canton, Bosnia and Herzegovina, recorded in the present
      study, may prove useful on planning the programs of pediatric health care in the
      region.

PMID- 19382637
TI  - [Clinical trials of the new skin test Diaskintest for the diagnosis of
      tuberculosis].
AB  - A new reagent for a skin test given the name Diaskintest has been designed for
      the screening diagnosis of tuberculosis and preclinical and clinical trials
      conducted. Preclinical trials were carried out on 315 laboratory animals (guinea
      pigs, albino mice). The reagent Diaskintest was ascertained to be nontoxic, to
      have no sensitizing properties, to be safe and specific, and to induce no
      positive reactions in BCG-vaccinated animals and healthy guinea-pigs. Its
      specific activity was comparable with that of the national reference--purified
      tuberculin PPD-L-2. With progression of tuberculous lesions, the guinea-pigs
      showed higher responses to Diaskintest dilution and the BCG-vaccinated animals
      lacked responses to Diaskintest with increased delayed type hypersensitivity. The
      clinical trial was permitted by the Federal Service for Surveillance in Health
      Care and Social Development of the Russian Federation. Clinical trials were
      conducted in 150 persons. The safety, specificity, sensitivity of Diaskintest
      were first examined in the clinical studies and its action was compared with the
      results of tuberculin skin test (Mantoux test) with 2 TE of PPD L-2. Diaskintest
      was ascertained to be highly sensitive when given in a dose of 0.2 microg in 0.1
      ml. In patients with active tuberculosis and new cases of Mycobacterium
      tuberculosis infection, the agent induced a positive skin reaction (a papule of
      more than 10 mm) in 98-100% of cases (p < 0.05). The agent caused no reaction
      associated with BCG vaccination. The specificity of the test was 93-100% with 95%
      significance. The rate of overexuberant reactions (vesicular necrotic changes,
      lymphangitis, and lymphadenitis) was 4-14% with 95% significance. Tuberculosis
      patients with significant immunopathological disorders might have no skin
      sensitivity to Diaskintest, as to PPD L-2 (a negative test). The findings
      substantiate the use of Diaskintest for mass epidemiological surveys for the
      differential diagnosis of tuberculosis and BCG vaccination-associated
      complications. The agent may be also used to evaluate the activity of the process
      in patients with tuberculosis and the efficiency of treatment in combination with
      other methods and to make a differential diagnosis of tuberculosis.

PMID- 19382638
TI  - [Nonspecific lung diseases in patients with pulmonary tuberculosis (issues of
      their prevalence, diagnosis and treatment)].
AB  - The paper gives data on the prevalence of nonspecific lung disease in patients
      with pulmonary tuberculosis, the specific features of diagnosis and treatment of
      their concomitance in 3453 patients with pulmonary tuberculosis. It shows the low
      detection rate of nonspecific lung diseases in patients with pulmonary diseases.
      The high error rate has been established in the diagnosis of pulmonary
      tuberculosis at health care facilities. There is evidence that the use of current
      therapy for bronchial obstructive syndrome with inhaled cholinolytics and beta2
      agonists in patients with pulmonary tuberculosis causes a reduction in the
      intensity of respiratory symptoms and an increase in forced expiratory volume in
      one second.

PMID- 19382639
TI  - [Cardiac damage in sarcoidosis: clinical features and impact of steroid therapy].
AB  - Twenty-seven sarcoidosis patients with signs of cardiac damage were examined to
      study the clinical features of cardiac sarcoidosis and the impact of systemic
      glucocorticosteroid (GCS) therapy on its course. ECG and echoECG changes were
      observed in 21 (78%) and 17 (63%) patients, respectively; abnormal perfusion was
      seen in 25 (93%) patients at single-photon emission myocardial computed
      tomography using 99mTc-MIBI. Three clusters (clinical types) of patients were
      identified, which differed in the pattern and degree of cardiac disorders. The
      use of systemic GCSs in 13 of 20 patients resulted in myocardial perfusion
      recovery and clinical improvement, the degree and duration of which depended on
      what cluster it belonged to. Seven GCS-untreated patients had progressive
      perfusion disorders with subsequent or synchronous clinical deterioration (p <
      0.05). The degree and duration of the positive effect of a GCS differed depending
      on the clinical type of cardiac damage.

PMID- 19382640
TI  - [Trends in major tuberculosis epidemiological indices in Armenia over 10 years
      (1997-2006)].
AB  - The authors studied statistical data on the trend in quantitative and qualitative
      tuberculosis epidemiological indices in Armenia in the period of 1997 to 2006.
      They ascertained a 1.7-fold rise in the incidence and prevalence of tuberculosis
      per 100,000 (from 27.8 to 48.6 and from 103.8 to 176.1), by preserving the
      mortality rates at the same level (4.3). However, morbidity rates have become
      steady-state in the past 2 years. Along with this, that was a slight
      deterioration in the qualitative indices--new tuberculosis cases showed increases
      in the proportion of destructive forms from 62.9 to 67.7%, bacteria-discharging
      persons from 70 to 75.9%, extrapulmonary forms from 7.3 to 9.3%, childhood
      morbidity from 9.6 to 19.1% with reductions in their proportion among all
      detected patients from 12.2 to 9.9%; an increase in the proportion of deceased
      persons within the first year of the disease from 20.6 to 35.0% and in postmortem
      diagnosis rates from 0.7 to 0.8%. The cure rates comprised an increase in cavern
      closure rates from 55.4 to 66%, with the preservation of bacterial discharge
      cessation at the level of 73-74%, a reduction in mortality rates among both new
      cases from 3.5 to 2.5 and the contingent of tuberculosis patients from 4.8 to
      3.5%, a 3.3-fold rise in early recurrences (from 0.9 to 1.3 per 100,000). The
      further task of the republic's antituberculosis service, planned by the authors,
      is to improve work in actively detecting tuberculosis in risk groups and
      treatment monitoring in patients with tuberculosis.

PMID- 19382641
TI  - [The course and treatment and efficiency of surgical treatment for disseminated
      pulmonary tuberculosis].
AB  - Chemotherapy for disseminated tuberculosis by the schemes regulated by the Order
      "On Improvement of Tuberculosis-Controlling Measures in the Russian Federation"
      issued by the Ministry of Health of the Russian Federation under No. 109 on March
      21, 2003, leads to the regression of intoxication syndrome and the normalization
      of general blood analysis parameters in most patients, provides bacterial
      excretion cessation in 72.7% of the patients and decay cavity closure in 53.8%.
      The extent of the process, the presence of multiple decay cavities, and the
      detection of drug resistance are the main causes of ineffective treatment in
      patients with disseminated tuberculosis.

PMID- 19382642
TI  - [Surgical treatment for pulmonary tuberculosis with Mycobacterium resistance to
      drugs].
AB  - The results of surgical treatment were analyzed in 481 patients who had been
      preoperatively found to have drug resistance. Patients with fibrocavernous,
      cirrhotic tuberculosis, chronic pleural empyema, and cavernous pneumonia
      constituted the vast majority (83.2%). Chemotherapy was performed by individual
      schemes, by taking into account MBT susceptibility. Glutoxim and pentaglobin were
      used as pathogenetic therapy for immunity correction. Resection-type operations
      [n = 368 (68.9%)], thorocoplastic interventions [n = 78 (14.6%)], thoracostomy or
      cavernostomy [n = 35 (6.5%)], pleurectomy [n = 26 (4.9%)], operation on the stump
      of the main bronchus [n = 15 (2.8%)], and mediastinal lymphadenectomy [n = 12
      (2.2%)] were predominant. Postoperative complications occurred in 15.5% of cases;
      mortality was 1.7%. The mycobacterium resistance to drugs verified by laboratory
      studies exerted no evident impact on the number and pattern of postoperative
      complications. The results of treatment depended on the extent and presence of
      complications of a tuberculous process, comorbidity, suppressed immunity, and the
      scope of a surgical intervention.

PMID- 19382643
TI  - [The course of a process and the efficiency of treatment of pulmonary
      tuberculosis patients excreting Mycobacterium tuberculosis with extensive drug
      resistance to antituberculous drugs].
AB  - Forty-one pulmonary tuberculosis patients (32 males and 9 females) excreting
      Mycobacterium tuberculosis (MBT) with extensive drug resistance to
      antituberculous drugs were examined. The process was first detected in 14.6% of
      the patients. At the previous stage of treatment, the vast majority of patients
      (85.4%) received antituberculous drugs. Fibrocavernous tuberculosis was a
      predominant form (73.1%). The acutely progressive course of the process was
      observed in 29.3% of patients. Lung destructive changes and bacterial excretion
      were revealed in all (100%) patients. Resistance to streptomycin, isoniazid,
      rifampicin, and fluoroquinolones was seen in all (100%) patients. The fact that
      in this cohort of patients the resistance of MBT to reserve drug, such as
      kanamycin, amikacin, and cycloserine, is observed at a rather high rate (from
      58.5 to 73.1%) is concerned about. For evaluation of the efficiency of treatment,
      all the examinees were divided into 2 groups, which were equal in clinical and
      laboratory characteristics. Group 1 patients (n = 19) were given chemotherapy
      regimen 2b (in new cases of tuberculosis) and individual chemotherapy regimens.
      Collapse therapy was additionally used in the treatment of Group 2 patients (n =
      22). After 3-month chemotherapy, negative sputum was established in 4 (9.8%) and
      6 (14.6%) patients in Groups 1 and 2, respectively. Following 6-month therapy,
      MBT excretion ceased in 13 (31.7%) and 15 (36.6%) patients in Groups 1 and 2,
      respectively. After 3- and 6-month therapy, decay cavity closure occurred in 2
      (4.8%) and 7 (17%) Group 1 patients and in 4 (9.8%) and 15 (36.6%) Group 2
      patients, respectively (p < 0.05).

PMID- 19382644
TI  - [Comparison of radionuclide studies with pleural morphological changes in
      patients with tuberculosis pleurisy].
AB  - Forty-seven patients with pleurisy of tuberculous etiology underwent a
      radionuclide study using the reagent 99mTc-labeled technefit, the result of which
      was compared with the morphological changes in the pleural biopsy or resection
      specimens. First-degree pleural resorptive dysfunction (PRD) was ascertained in
      27.6% of the patients. Morphologically, there were signs of acute edema of all
      pleural layers in both the area of inflammation and the proximal portions with
      reduced vessels in the microcirculatory bed (MCB). These patients had medical
      treatment. 59.6% of patients had second-degree PRD--circumscribed caseous foci
      and granulomas were morphologically found in the presence of progressive fibrosis
      with a small number of vessels in the MCB. 12.8% of patients had third-degree PRD
      -massive pleural fibrosis with a significant reduction in MCB vessels and lymph
      capillaries. Active tuberculous inflammation remained mainly in the deep layers
      of the pleura. Surgical treatment was performed in patients with second-third
      degree PRD. Thus, comparison of the results of a radionuclide study with
      morphological changes in the tuberculosis-afflicted pleura made it possible to
      establish the degree of pleural MCB impairments, to characterize the activity of
      a pathological process, and to define objectively treatment policy.

PMID- 19382645
TI  - [Evaluation of hepatic function in new cases of pulmonary tuberculosis due to the
      use of standard chemotherapy regimens I and IIB].
AB  - The frequency and magnitude of hepatotoxic reactions were compared in 147 new
      cases of pulmonary tuberculosis within the first three months of chemotherapy
      (CT) by standard regimen 1 [H, R, Z, S (E)] (Group 1) and regimen 2B [the same
      drugs + kanamycin (amikacin) and fluoroquinolones] (Group 2). Their efficiency
      was evaluated from 6 serum indices--the level of bilirubin, the activities of
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline
      phosphatase (AP), and gamma-glutamyl transpeptidase (GGTP), and thymol test
      results. Tests were monthly carried out. The results were separately analyzed in
      patients with and without baseline abnormalities in the indices being tested.
      Within the first two months of CT, the patients without baseline abnormalities
      showed the slightly higher frequency and magnitude of hepatotoxic reactions on
      receiving regimen 2B. Following 3 months of CT combined with hepatoprotectors,
      the patients treated by standard regimen 1 had solitary laboratory signs of
      hepatic damage, but there was a regular elevation of GGTP in the regimen 2B
      group. After a month of regimen 1 CT in combination with hepatoprotectors, the
      patients with baseline abnormalities has positive changes in all the studied
      indices. In the patients treated by regimen 2B in combination with
      hepatoprotectors, the changes were the same, except for GGTP that remained to be
      at the increased baseline levels. Following 2 months of CT, in Group 1 positive
      changes continued in the studied markers and, with regimen 2B treatment, abnormal
      changes began increasing again. After 3 months abnormal changes were single in
      the markers of hepatic damage with regimen 1 treatment and there was a repeated
      significant rise in the values of AP and GGTP with regimen 2B. It is concluded
      that in addition to ALT and AST, GGTP is of great informative value in
      controlling the hepatotoxic effects of CT.

PMID- 19382646
TI  - [Osteal scintigraphy in the evaluation of the course of reparative processes
      after surgical treatment for tuberculous and nonspecific arthritis, by using
      constrained bone grafting].
AB  - Osteal scintigraphy was used to study the course of reparative processes after
      surgical treatment in 106 patients with large joint lesions, including 76
      patients with tuberculous arthritis and their sequels and 30 with nonspecific and
      dystrophicones before and 2-3 weeks after operations (those with and without
      articular tissue revascularization (n = 43 and n = 63); mobilizing (n = 64) and
      stabilizing (n = 42) operations), of them 22 being performed in late periods (1-3
      years (n = 16)). It was established that after mobilizing operations with
      revascularization, the early postoperative period was marked by a significant
      increase in radionuclide accumulation (by 1.52 times) and after those without
      revascularization, there was a less significant rise (by 1.34 times); following
      stabilizing operations with revascularization, hyperfixation was similar before
      and after surgery whereas following those without revascularization it
      significantly reduced (by 1.53% in 70% of patients). The late postoperative
      period was characterized by reduced hyperfixation, which was more evident after
      mobilizing operations with revascularization. Osteal scintigraphy quantifies the
      course of reparative processes and determines the efficiency of different
      operations.

PMID- 19382647
TI  - [Psychologic and physiologic evaluation of functional state in engineering
      personnel under variable work intensity conditions].
AB  - Evaluating psychologic state, functional state of nervous and cardio-vascular
      systems in engineering personnel of electric energetic company, the authors
      assessed influence of work intensity on psychic and functional state of the
      examinees. The data obtained helped to define a list of informative parameters
      that demonstrate a decline in psychic and functional resources, development of
      emotional burnout syndrome, during increase in mental work intensity.

PMID- 19382648
TI  - [Multiple local involvement of peripheral nerves in workers suffering from
      occupational hands disorders].
AB  - Stimulation and needle electromyography studies covered 102 patients with
      occupational hands disorders. 87% of the examinees showed tunnel syndromes signs:
      44% of those had one tunnel syndrome, 36% - two synromes, and 7% - multiple ones.
      The results failed to demonstrate reliable difference in tunnel syndrome
      frequency for vibration exposure and functional hands overstrain. Sensitivity
      thresholds in vibration disease were increased in 86.7% of the examinees and in
      61.5% of those with functional hands overstrain. Peripheral nerve disorders in
      residual defects with occupational hands diseases are persistent due to
      compression within physiologic tunnels.

PMID- 19382649
TI  - [Early diagnosis and complex management of neurologic signs of vibration disease
      in miners].
AB  - Vibration disease in miners is characterized by various neurologic signs:
      vegetative sensory polyneuropathy, cerebral and vertebrogenic symptoms.
      Antioxidant medications help to increase efficiency of therapeutic and preventive
      measures in vibration disease.

PMID- 19382650
TI  - [Influence of vibration on biochemical values characterizing oxidative
      metabolism, immunity, metabolism in muscular and connective tissues (review of
      literature)].
AB  - The authors reviewed literature on molecular aspects of vibration effects in
      workers. Findings are that apparently healthy workers demonstrate changes in
      oxidative metabolism, rheological properties of blood, increased RBC membrane
      permeability, higher urinary level of substances characterizing muscular and
      connective tissues dystrophy.

PMID- 19382651
TI  - [Expert evaluation--measures to objectivize subjective opinion].
AB  - Reliability of expert evaluation remains a topical problem for occupational
      medicine, industrial ecology, ergonomics, psychology, sport refereeing and
      special examinations without instrumental assessment of work state, conditions,
      their jeopardy, etc. In this connection, the algorithm of mathematic and
      statistic processing of subjective opinions increases objectivity of expert
      evaluation of such parameters.

PMID- 19382652
TI  - [The analysis of the medical demographic processes in the Krasnodar Kray].
AB  - The results of analysis of the medical demographic indicators from 1990 to 2006
      in the Krasnodar Kray are presented. The data provides an opportunity to develop
      the practical suggestions to enhance the population life quality and to elaborate
      the efficacious measures for preventing mortality and developing favorable
      conditions for fertility increase. The comparative indicators of birth rate and
      death rate dynamics are presented.

PMID- 19382653
TI  - [The social medical characteristics of families bringing up the disabled
      children].

PMID- 19382654
TI  - [The social hygienic characteristics of the disabled persons employment
      assistance].

PMID- 19382655
TI  - [The medical sociological analysis of the factors affecting the mortality with
      taking into consideration the gender and age differences].
AB  - The issue of various factors affecting the mortality rate of population in the
      light of the gender and age differences is considered. The medical demographic
      and medical sociological statistical data of mortality is presented in its
      ontogenesis and is differentiated according time periods. The issue of death-rate
      among the mentally ill patients depending on their gender characteristics is
      discussed. The focal point in the article is the evaluation of association
      between the age of parents and the longevity of posterity. The data revealing the
      relationship between mother's age and the risk of mental disease development is
      provided.

PMID- 19382656
TI  - [The prospective model of human resources' management in health institution].
AB  - The article postulates the actuality of developing the concept of the
      psychological aspects of institution management as projected into health care
      area where the medical personnel is working in the conditions of higher
      responsibility, emotional and intellectual overloads under permanent nervous
      psychological stress. This contingent of medical institutions stuff very often
      ignore the positive psychological interventions both due to the poor labor
      management and the corresponding knowledge lacking. The topicality of this
      research vector is determined by the deficiency of the human resources'
      management studies in the public health field. The need in searching the
      investigation prospective directions is ascertained by the unexploredness of
      personnel management in national health care.

PMID- 19382657
TI  - [The organizational approaches to the quality management in the laboratorial
      examinations].
AB  - The results of the quality investigation of laboratory services operations of the
      city of Saratov and Saratov Oblast are presented. The issue of organization and
      quality of carrying out the laboratorial examinations is analyzed. The
      suggestions related to the clinical laboratorial examinations quality management
      are exposed.

PMID- 19382658
TI  - [The organization of tuberculosis detection among population].

PMID- 19382659
TI  - [The primary prevention of oncological gynecological pathology in the involution
      period of life].

PMID- 19382660
TI  - [The effectiveness of prevention of the pathologic health states among
      adolescents residing in the conditions of rural area].
AB  - The municipally-oriented system of health prevention to implement the process of
      management of adolescent pathology in rural area was developed. The medical,
      social and economical effectiveness of this system was established. The evident
      interdependence between the adolescents' health losses and the level of
      preventive activities' effectiveness is revealed.

PMID- 19382661
TI  - [From the history of Russian physicians societies in Harbin: 1920-1930].

PMID- 19382662
TI  - [M. H. Akhutin, a prominent war field surgeon: to the centenary and tenth
      anniversary].

PMID- 19382663
TI  - Epidemiology of human cytomegalovirus strains through comparison of
      methodological approaches to explore gN variants.
AB  - Genomic variation among human cytomegalovirus (HCMV) wild-type strains is a well
      documented phenomenon probably implicated in HCMV-induced immunopathogenesis.
      Extensive genetic polymorphism has been detected for the envelope glycoprotein N
      (gN) and HCMV clinical isolates have been clustered into seven distinct gN
      variants (gN-1, gN-2, gN-3a, gN-3b, gN-4a, gN-4b, gN-4c). Several studies from
      different research groups worldwide have addressed this topic using different
      methodological approaches (PCR-RFLP, PCR-Cloning, PCR-Sequencing) and sometimes
      yielding apparently conflicting results. This paper analyses the epidemiology of
      HCMV strains through analysis of gN variants, criticizing the methodological
      approaches and study populations by comparison of published reports.

PMID- 19382664
TI  - Human herpesvirus 8 seroprevalence among internationally adopted children coming
      from Eastern Europe.
AB  - The seroprevalence of Human Herpes Virus 8 (HHV8) and its transmission pattern
      were assessed testing serum samples of 120 internationally adopted children (aged
      1-15 years) coming from Eastern Europe. Determinations of IgG antibodies against
      both latent and lytic HHV-8 antigens were performed by indirect
      immunofluorescence assay. Antibodies were detected only for lytic antigen of the
      virus in 12.5% of children with a seroprevalence significatively higher (19.6%)
      in young children (age 1-6). No correlation was observed between HHV8
      seropositivity and serological markers for hepatitis A, B and C viruses and Human
      Immunodeficiency virus. In conclusion, our findings suggest that HHV8 infection
      is widespread in some populations from the East Europe, and that person to person
      contacts among children could be considered the predominant mode of HHV8
      transmission in younger age.

PMID- 19382665
TI  - Antibiotic susceptibility profile of Aeromonas spp. isolates from food in Abu
      Dhabi, United Arab Emirates.
AB  - A total of 57 Aeromonas isolates from food samples such as fresh and frozen
      chicken, game birds, pasteurized milk, baby food, bakery products, fruit and
      vegetables, fish, and water from Abu Dahbi, UAE were investigated for antibiotic
      susceptibility profile. Most strains were resistant to penicillins (ticarcillin,
      mezlocillin, oxacillin, piperacillin), sulfamethoxazole, trimethoprim and
      macrolides (erythromycin, vancomycin, clindamycin) but sensitive to tetracycline,
      chloramphenicol, nitrofurantoin, aminoglycosides (amikacin, gentamicin,
      tobramycin), cephalosporins (cefuroxime, ceftrioxone, cefazolin, cephalexin,
      cephalothin, cefoxitin, cefotaxime), quinolone (ciprofloxacin), colistin sulphate
      and SXT (trimethoprim-sulfamethoxazole). On the other hand, many antibiotics
      showed excellent inhibitory activity (>75% strains were sensitive to them)
      against all the strains tested. These include cefuroxime, ceftrioxone,
      ciprofloxacin, colistin, amikacin, gentamicin, tetracycline, chloramphenicol,
      nitrofurantoin, cefotaxime and tobramycin. In conclusion, the results show a
      detailed pattern of sensitivity of the various Aeromonas spp. isolates to a
      variety of antibiotics and provide useful information in the context of selective
      isolation and phenotypic identification of the aeromonads from food.

PMID- 19382666
TI  - Predictive value of clinical and laboratory findings in the diagnosis of the
      enteric fever.
AB  - Although the definitive diagnosis of enteric fever requires the isolation of
      Salmonella enterica serotype typhi or paratyphi, the diagnosis is usually made
      according to clinical and laboratory findings. There is usually a diagnostic
      dilemma. The aim of this study was to determine the minimum required parameters
      that could be valuable in the diagnosis of enteric fever. A retrospective study
      was performed to compare the clinical and laboratory findings in 60 patients who
      proved to have enteric fever by cultures and 58 patients with non-enteric fever.
      Features independently predictive of enteric fever were assessed by multivariate
      logistic regression. Sensitivity, specificity and positive predictive and
      negative predictive values were estimated. Significant clinical features of
      enteric fever were hepatomegaly, splenomegaly, relative bradycardia, rose spots,
      leucopenia, trombocytopenia, eosinopenia and elevated AST level. Five of these
      features were found to be predictive for the diagnosis of enteric fever;
      splenomegaly, relative bradycardia, rose spots and trombocytopenia and elevated
      AST level. In conclusion, clinical and laboratory findings can help the clinician
      to diagnose enteric fever in the absence of microbiological confirmation.

PMID- 19382667
TI  - Patterns of drug resistance in pulmonary tuberculosis cases in the Izmir
      district, Turkey.
AB  - Antituberculosis drug resistance patterns were investigated among the new and
      previously treated pulmonary tuberculosis (TB) cases in Izmir district,
      retrospectively. Proportions of resistance patterns were determined using a
      number of resistant cases using as a denominator. Resistance to at least one drug
      was found in 304 (29.7%) patients in 1023 a total of tuberculosis cases. 182 new
      and 82 previously treated consecutive pulmonary tuberculosis cases were
      investigated. Patterns were examined as single and/or probable combinations of
      isoniazid (H), rifampicin (R), ethambutol (E) and streptomycin (S). Single drug
      resistance mode, mono S, and HS resistance patterns were the highest proportions
      in comparison with other modes and patterns in both new and previously treated
      cases. HRS pattern showed a significant proportion and proportions of quadruple
      mode were higher than triple mode in previously treated cases. Proportions of
      patterns associated with R were detected more than expected. Surveillance of
      proportions of anti-TB drug resistance is important as well as surveillance of
      resistance rates.

PMID- 19382668
TI  - Tuberculosis and immigrants: a SIMIT (Italian Society of Infectious Diseases)
      clinical, epidemiological multicentric research investigation.
AB  - The aim of the study was to evaluate the epidemiology and the diagnostic,
      clinical and therapeutic aspects of immigrants affected by tuberculosis,
      hospitalized in 35 Italian Infectious Diseases Clinics during 2003. The data
      obtained showed that 300/2392 (12.5%) patients had active tuberculosis, 10.3% of
      whom had concomitant HIV infection. 53% of the patients were legal residents and
      were assisted by the National Health Service; 48.3% came from African regions.
      The mean length of residency in Italy at the time of hospitalization was 4 years.
      The main clinical forms were pulmonary (66%), lymph nodal (15.3%) and bone TB
      (5.3%). Drug resistance was demonstrated in 16% of cases with 9% cases of
      resistance to isoniazid, 8.2% to streptomycin, 5.1% to pyrazinamide, 2.6% to
      ethambutol, 2.6% to rifampicin; in 5.3% of cases a multiple resistance was
      demonstrated. A complete adherence to treatment was achieved in 213 patients.
      Statistical analysis disclosed a significant correlation between compliance with
      treatment and legal citizenship status. In conclusion, TB still represents an
      important disease among immigrants. Improved living conditions, both in countries
      of origin and in Italy, especially in the first few years, would certainly
      decrease the incidence of TB.

PMID- 19382669
TI  - In vitro activities of piperacillin or cefoperazone alone and in combination with
      beta-lactamase inhibitors against gram-negative bacilli.
AB  - We investigated in vitro activities of piperacillin or cefoperazone alone and in
      combination with beta-lactamase inhibitors against Gram-negative bacilli.
      Piperacillin/tazobactam 8:1 lowered resistance for Escherichia coli, Serratia
      marcescens, Enterobactaer cloacae, Klebsiella pneumoniae and imipenem-susceptible
      Acinetobacter baumannii. When piperacillin was combined with sulbactam 2:1 or
      4:1, resistance against E. coli, S. marcescens, E. cloacae, extended spectrum
      beta-lactamase (ESBL)-K. pneumoniae and A. baumannii were reduced. MIC90 of
      cefoperazone against S. marcescens, E. cloacae, ESBL-K. pneumoniae and A.
      baumannii were >128 mg/L. Addition of sulbactam 1:1 or 2:1 enhanced antimicrobial
      activities. Addition of sulbactam to piperacillin or cefoperazone enhanced
      antimicrobial activities of GNB.

PMID- 19382670
TI  - An in vitro and ex vivo study on two antibiotic-based endodontic irrigants: a
      challenge to sodium hypochlorite.
AB  - Amongst the bacterial species which most often cause endodontic failures,
      Enterococcus faecalis is the most important. This study compared the
      effectiveness of sodium hypochlorite and two new generation antibiotic-based
      endodontic irrigants, Tetraclean and MTAD. By means of an in vitro agar dilution
      assay, we show that both Tetraclean and MTAD are 100% effective against 54
      clinical isolates at dilutions up to 1:256 and 1:1048, respectively, whereas
      sodium hypochlorite completely loses its effectiveness when diluted more than 32
      times. The bactericidal effect of both Tetraclean and MTAD can be ascribed not
      just to their antibiotic component per se, but also to a synergistic effect among
      the several ingredients included in the formulations. Moreover, by an ex vivo
      model of teeth extracted and experimentally infected with E. faecalis ATCC 29212,
      we show that both the antibiotic-based endodontic irrigants are effective in
      eliminating bacterial cells in 93 to 100% of the test samples. The results of
      these pre-clinical studies strongly support a wider use of this new group of
      endodontic irrigants in daily clinical practice.

PMID- 19382671
TI  - Prevalence and spread of pseudomonas aeruginosa and Klebsiella pneumoniae strains
      in patients with hematological malignancies.
AB  - The aim of the study was to determine the prevalence of Pseudomonas aeruginosa
      and Klebsiella pneumoniae strains in patients with acute leukemias, to assess
      their clinical significance, and to define the sources and ways of their spread
      using genetic analysis. Thirty-four patients were investigated during the
      observed period. Twenty-one strains of Pseudomonas aeruginosa and 35 strains of
      Klebsiella pneumoniae were isolated from patient samples. In the case of
      Pseudomonas aeruginosa, 47.6% of strains were identified as pathogens and caused
      infection. By contrast, only 4 isolates (11.4%) of Klebsiella pneumoniae could be
      regarded as etiological agents of bacterial infection. Based on the obtained
      results, Klebsiella pneumoniae strains are assumed to be of mostly endogenous
      origin. In the case of Pseudomonas aeruginosa strains, the proportion of
      identical strains detected in various patients was higher and exogenous sources
      were more significant. In addition, our results confirmed the ability of
      Pseudomonas aeruginosa strains to survive on a particular site in the hospital
      for a longer time.

PMID- 19382672
TI  - Water quality and ecological status of the Alcantara River estuary (Italy).
AB  - The Alcantara River estuary was studied to obtain the first data on both water
      quality and ecological status of the only River Park in Sicily (Italy). Water
      samples were seasonally collected from three selected stations in the estuarine
      area and from one station at the mouth of the estuary in the marine coastal zone.
      Picoplankton and picophytoplankton counts were among the highest observed in
      estuarine environments and in other coastal waters of the Mediterranean Sea. The
      contribution of picophytoplankton to total picoplankton showed greater variations
      in freshwater (from 0.53% to 8.6%) than in coastal waters (from 1.8% to 4.3%).
      Picophytoplankton abundance increased in Alcantara waters in winter. Vibrio and
      Aeromonas spp. abundances ranged from x10(2) to x10(3) CFU 100 ml(-1) and from
      x10(3) to x10(5) CFU 100 ml(-1) respectively. Vibrio and Aeromonas spp. counts
      were independent from the fecal contamination level. Bacterial identification of
      the isolates revealed the presence of pathogenic and potentially pathogenic
      Vibrio and Aeromonas spp. for humans and animals.

PMID- 19382673
TI  - Surveillance of toxoplasmosis in pregnant women in Albania.
AB  - This study presents the initial results derived from a collaborative project
      aimed at the surveillance of the toxoplasma infection in a population of 496
      Albanian pregnant women. From October 2004 to March 2005, serum samples were
      tested to detect IgG, IgM and IgG avidity for toxoplasmosis. Of the 496 pregnant
      women examined, 241 (48.6% [range 44-53]; IC 95%). resulted positive for IgG,
      three of whom (1.3%) were also positive for IgM. As the preliminary results of
      our survey disclose the absence of an efficient pre-gravidic screening and
      counseling for the prevention of toxoplasmosis in Albania, we propose a health
      education program for all pregnant women, together with serological testing
      (screening) for those exposed to predictors of toxoplasmosis infection as an
      epidemiological support and financially sustainable alternative.

PMID- 19382674
TI  - Serological and entomological survey of zoonotic visceral leishmaniasis in
      Denizli Province, Aegean Region, Turkey.
AB  - A cross-sectional seroepidemiological survey of leishmaniasis was carried out
      among children and adults from four villages and one district of Denizli province
      located in the Southern Aegean Region of Turkey where 14 human visceral
      leishmaniasis (HVL) cases including 4 adults were reported between 1993 and 2000.
      Blood samples were taken from 329 children, 217 adults and 140 dogs and a
      physical examination was also done. Indirect fluorescent antibody test and enzyme
      linked immunosorbent assay were performed for all sera. All 329 sera collected
      from children were found to be negative while 2 (0.09%) out of 217 adult sera
      were found to be seropositive. One seropositive adult patient was confirmed
      parasitologically as HVL after bone marrow aspiration and treated with AmBisome
      while the other was followed only serologically because of the absence of
      symptoms. The overall canine leishmaniasis seroprevalence was found to be 20.7%.
      Sand flies were collected using CDC light traps in three out of five study sites
      and midguts of females were checked for promastigotes after
      dissection/identification. Eight Phlebotomus species were found in the region.
      Phlebotomus neglectus and P. papatasi were determined as dominant species with
      the ratio of 43.52% and 37.35%, respectively. No promastigotes were found in the
      midgut specimens. In addition, the results showed the presence of vector sand fly
      species, as well as a high seroprevalence of anti-Leishmania antibodies among
      dogs from rural and a suburban area of Denizli province with a large proportion
      of asymptomatic seropositive dogs.

PMID- 19382675
TI  - Support for the role of Candida spp. in extensive caries lesions of children.
AB  - Candida spp. are frequently detected in the mouths of children with extensive
      caries lesions compared with caries-free subjects. In this study we evaluated the
      presence of Candida spp. in association with mutans streptococci and lactobacilli
      in the saliva of children with dental decay, before and after anti-caries
      treatment. Samples of saliva from 14 children with caries lesions and from 13
      caries-free subjects were evaluated for the presence of mutans streptococci,
      lactobacilli and Candida spp. by culture. Eleven of 14 carious subjects hosted
      Candida spp. in their saliva as against only 2 out of 13 subjects without caries
      lesions. Carious subjects were treated by adopting a conventional protocol for
      caries disease (rinses with a mouthwash containing 0.2% chlorhexidine and
      fluorine). After treatment, the salivary bacterial counts decreased for mutans
      streptococci and in some cases for lactobacilli, but large numbers of Candida
      spp. remained in the saliva of several children. The latter were treated with the
      antifungal drug nystatin (oral rinses) and evaluation of the level of yeasts in
      the saliva showed disappearance of the microorganism in several cases. The
      results indicate that antiseptic treatment alone for dental decay is not
      sufficient for the eradication of microorganisms potentially responsible for
      caries lesions, in particular when yeasts are present. We hypothesize that the
      oral cavity of children could act as a reservoir of fungi, and eradication could
      be needed to prevent both exacerbation of caries lesions, and colonization by
      Candida spp. of other host sites.

PMID- 19382676
TI  - A candidate modified-live bovine coronavirus vaccine: safety and immunogenicity
      evaluation.
AB  - A modified-live vaccine against the respiratory form of bovine coronavirus (BCoV)
      infection was developed by progressive attenuation of a respiratory strain
      (438/06-TN). The vaccine was found to be safe as four colostrum-deprived newborn
      calves remained healthy after oronasal administration of ten doses of the
      vaccine. The immunogenicity of the vaccine was assessed by intramuscular
      injection of one vaccine dose to 30 BCoV-antibody negative 2-3-month-old calves.
      At 30 days post-vaccination, all vaccinated calves displayed high antibody titres
      against BCoV. Sequence analysis of the S gene of wild-type and cell-adapted
      438/06-TN strain detected 10 nucleotide changes, 9 of which were non-synonymous.

PMID- 19382677
TI  - What role for human rhinoviruses in the lower respiratory tract?
AB  - Human rhinoviruses (HRV) usually cause upper airway infections. However, viral
      replication in the tracheobronchial tree has been disclosed, although its
      clinical role is poorly known. We evaluated the prevalence of HRV in 159
      bronchoalveolar lavages from 88 patients and describe a lung transplant recipient
      with a high HRV load in association with acute rejection. HRV was detected in
      22/88 patients (25.0%): 7/18 lung transplant recipients, 11/41 immunocompetent,
      and 4/29 immunocompromised (p = n.s.). No lung disease was significantly
      associated with HRV positivity. It should be recommended to include HRV in the
      virological diagnostic work-up of lower respiratory specimens to elucidate their
      role.

PMID- 19382678
TI  - Six cases of sepsis caused by Pantoea agglomerans in a teaching hospital.
AB  - Pantoea agglomerans is an environmental organism which may seldom cause
      opportunistic infections. Here we report on a 6 case outbreak in a teaching
      hospital. Within three months . agglomerans was isolated from blood cultures of 5
      patients from oncology and 1 patient from ICU departments. P. agglomerans was in
      pure culture in 5 cases, while in the last one Rahnella aquatilis and Candida
      famata were also isolated. Therefore, P. agglomerans is able to produce
      nosocomial infections in patients with primary pathology often associated with
      immune suppression.

PMID- 19382679
TI  - Improvement of CXCR3 ligand CXCL11/I-TAC measurement in human plasma and serum.
AB  - The chemokine receptor CXCR3 is involved in cell trafficking dysregulation
      associated with several inflammatory conditions, including autoimmune and viral
      diseases. Downregulation of CXCR3, through binding with its ligand CXCL11 (I
      TAC), represents a key mechanism in lymphocyte recruitment. Determination of
      circulating I-TAC can provide useful information in the investigation of
      inflammatory/infectious conditions. The existing commercial kit does not measure
      CXCL11/I-TAC in complex matrices, such as human plasma and serum, as reliably as
      in in vitro-generated cell culture supernatants. We here describe means which
      lead to an improvement of CXCL11/I-TAC measurement in human plasma and serum.

PMID- 19382680
TI  - [Problems of sex determination in birds exemplified by Gallus gallus domesticus].
AB  - The current views of sex determination in birds are considered mostly with the
      example of Gallus gallus domesticus, the species best studied in this respect.
      Data on the appearance of primordial germ cells, their migration to the
      primordial gonads, the role of hormonal factors in the regulation of sex
      differentiation, the sex chromosomes, putative genetic mechanisms of sex
      determination, and a possible contribution of dosage compensation are described.
      The review discusses the two best-grounded hypotheses on the roles of the Z and W
      chromosomes in sex determination.

PMID- 19382681
TI  - [Agrobacterium-mediated transformation of plants: transfer of vector DNA
      fragments in the plant genome].
AB  - The review presents experimental data on the integration in the plant nuclear
      genome of vector sequences during Agrobacterium-mediated transformation. Main
      attention is given to the frequency and mechanisms of this event among transgenic
      plants. The factors influencing the frequency of this event, as well as the ways
      of developing special constructs for elimination of vector backbone sequences as
      undesirable from the point of view of commercial use of genetically modified
      plants, are considered.

PMID- 19382682
TI  - [Conditional lethal mutations shift the genome from stability to instability].
AB  - The phenomenology of genomic destabilization is described in Drosophila
      melanogaster mutants containing radiation-induced conditional dominant lethals in
      the X chromosome and in autosome 2. Destabilization manifests itself as (1) the
      loss or decrease of lethality of previously lethal mutations; (2) the loss of
      expression of visible dominant mutations in an opposite homolog; (3) chromosomal
      instability resulting in the loss of the X chromosome in germline and somatic
      cells; (4) the occurrence of novel mutations (secondary mutagenesis); (5) the
      occurrence of single and mass modifications; (6) disturbances in individual
      development (formation of morphoses). The key event for the shift of the genome
      from the stable state into the unstable one is the occurrence of a conditional
      dominant lethal mutation.

PMID- 19382683
TI  - [Conservative E(y)2/Sus1 protein interacts with the Su(Hw)-dependent insulators
      in Drosophila].
AB  - Insulators are regulatory elements having two properties. First, they are able to
      disturb the interaction between promoters and enhancers/silencers. Second, they
      are able to block distribution of the heterochromatin. The best-studied are the
      Su(Hw)-dependent insulators of Drosophila melanogaster, activity of which is
      determined by the Su(Hw) protein. In this study it was demonstrated that novel,
      evolutionary conservative transcription factor E(y)2/Sus1 interacted with the
      Su(Hw) zinc-finger domain and was present in the protein complex, associated with
      the Su(Hw)-dependent insulators.

PMID- 19382684
TI  - [The cnr-like operon in strain Comamonas sp. encoding resistance to cobalt and
      nickel].
AB  - Plasmid pBS501 was detected in the strain Comamonas sp. BS501. This plasmid
      specifies high level of induced resistance (5 mM) to cobalt/nickel both in the
      host strain and in related strains C. testosteroni B-1241 and C. acidovorans B
      1251. Hybridization analysis revealed a homology of pBS501 restriction fragments
      with the only well-characterized operon cnrXYHCBAT that resides in plasmid pMOL28
      from Cupriavidus metallidurans CH34. Essential differences in the structural
      organization of the cobalt/nickel resistance determinant were found between
      plasmid pBS501 and the cnr-operon.

PMID- 19382685
TI  - [Systemic control of the molecular, cell, and epigenetic mechanisms of long
      lasting consequences of stress].
AB  - Based on M.E. Lobashev's views of the systemic control of genetic and cytogeneitc
      processes and a substantial effect of excitability on plastic changes in the
      central nervous system (CNS), the effect of prolonged emotional and pain stress
      (PEPS) on the molecular, cell, and epigenetic mechanisms of injury memory was
      studied in rat strains bred for a certain excitability of the nervous system.
      PEPS was for the first time found to cause long-lasting (2 months) morphological
      alterations of the CA3 region of the hippocampus and to modify the genome
      activity of its pyramidal neurons. The two phenomena were potentiated by a
      genetically determined low functional state of the CNS. The post-stress
      regulation of the genome function in hippocampal neurons was mediated by changes
      in heterochromatin conformation, activation of methyl-CpG-binding protein (MeCP2)
      synthesis, and subsequent changes in acetylation of histone H4. Genetically
      determined high excitability of the nervous system proved to be a risk factor
      that affects the specifics and time course of the observed molecular, cell, and
      genetic transformations of neurons. The results provide for a better
      understanding of the epigenetic mechanisms of injury memory, which forms a
      pathogenetic basis for posttraumatic stress disorder and other human psychogenic
      conditions characterized by a prolonged duration.

PMID- 19382686
TI  - [Methylene blue as a supressor of the genotoxic effect of ultraviolet radiation
      with a wavelength of 300-400 nm].
AB  - Ultraviolet radiation with a wavelength of 300-400 nm is characteristic of
      sunlight at the earth surface and causes DNA damage mediated by energy transfer
      to O2 with the transformation of the latter in the singlet state. In connection
      with this, scavengers of reactive oxygen species (ROSs) are potential protectors
      against the genotoxic effect of this kind of radiation. It was found that the
      methylene blue dye at doses differing by several orders of magnitude from those
      that are toxic for humans is able to suppress completely the SOS response induced
      by UV with a wavelength of 300--400 nm in Escherichia coli.

PMID- 19382687
TI  - [Marker characters of variation induced in Triticum aestivum L. by nicotinic
      acid].
AB  - A search for markers of epigenetic variability in spring common wheat form
      Genotroph-1, obtained after the treatment of seeds and growing plants of spring
      common wheat cultivar Kazakhstanskaya-126 with nicotinic acid of innate origin
      (0.1-0.01% water solutions), and in a winter wheat line Gostianum-88 along with a
      common wheat cultivar Alem obtained on the basis of Genotroph-1 was conducted
      under laboratory conditions. The possibility of using isoenzymes as markers for
      studying variation induced by natural nicotinic acid with high frequency was
      demonstrated. Enzyme glutamate oxaloacetate transaminase-2, as a marker by which
      modified plants and lines obtained on the basis of these plants differ from the
      original cultivar, was identified.

PMID- 19382688
TI  - [A study of the storage proteins in the introgression lines of common wheat
      (Triticum aestivum L. x T. timopheevii Zhuk.) resistant to brown leaf rust].
AB  - Storage proteins, prolamins, were studied in ten introgression lines of common
      wheat bred with involvement of Triticum timopheevii Zhuk. and five commercial
      hexaploid wheat cultivars. The lines are resistant to leaf rust. A comparative
      analysis of the storage proteins in the Triticum aestivum L. introgression lines
      and the parental forms allowed us to (1) detect the active genes of prolamins on
      the chromosomes homeologous groups 1 and 6 in the introgression lines of T.
      aestivum and T. timopheevii; (2) clarify their origin; (3) identify the
      chromosome attribution of the products; (4) estimate the degree of introgression
      and postulate the introgression mechanisms; and (5) predict the bread-making
      quality of these introgression lines.

PMID- 19382689
TI  - [Agamospermy in outbred crosses of Fragaria vesca L. (Rosaceae)].
AB  - The seed progeny obtained in European wood strawberry Fragaria vesca L. (2n = 2x
      = 14) via outbred crosses proved to include matromorphic diploid plants, whose
      proportion varied from 10.0 to 21.0%. To allow their identification, the crosses
      were performed using recessive dihomozygotes (variety Alexandria) as a maternal
      form and dominant dihomozygotes as a paternal form. Generation of parthenogenetic
      plants in ourbred crosses with known genetic markers suggested pseudogamous
      agamospermy. The question is discussed as to whether seed development via
      agamospermy is possible in wild-growing F. vesca populations of Siberia. The
      capability of forming some seeds via agamospermy is considered to result from
      successful adaptation of the F. vesca reproductive system to stressful growth
      conditions.

PMID- 19382690
TI  - Genetic diversity across natural populations of Dendrobium officinale, the
      endangered medicinal herb endemic to China, revealed by ISSR and RAPD markers.
AB  - Dendrobium officinale is a rare and endangered herb with special habitats and
      endemic to China. Genetic diversity was examined within and among nine natural
      populations using inter-simple sequence repeat (ISSR) and random amplified
      polymorphic (RAPD) for conservation. Both molecular markers revealed a high
      percentage (>89%) of polymorphic bands and ISSR markers detected more diversity
      than RAPD markers. Analysis of molecular variance (AMOVA) revealed that 78.84%
      (ISSR) and 78.88% (RAPD) of variability was partitioned among individuals within
      populations. This genetic structure was probably due to severe genetic drift
      resulting from habitat fragmentation and human overexploitation since 1950s.
      Moreover, there is a lack of significant association between genetic and
      geographic distances (r = 0.276; p > 0.05) in the populations of D. officinale.
      From the conservation point of view, populations GL, GS and GSD with higher
      genetic diversity should be protected firstly to maintain the species potential
      for evolutionary change and population YG with lower diversity but representing a
      novel evolutionary unit should also be paid more attention to during D.
      officinale conservation practice.

PMID- 19382691
TI  - [The gene pool of the Belgorod oblast population: Malecot's isolation-by-distance
      parameters].
AB  - The mean distance between birthplaces of spouses (sigma, sigma'), the proportion
      of medium migrations (k), and the effective migration pressure (M(e)) have
      considerably increased, and the linear systematic pressure coefficient (b) has
      decreased in the human population of the Central Chernozem region during the past
      50 years. However, the local inbreeding level (a), which is determined by both an
      increase in the migration intensity and a decrease in the effective population
      size (N(e)), has remained practically unchanged. A change in the regional
      administrative structure has affected the genetic structure of populations. In
      the 1950s, raions (administrative districts) of Kursk and Voronezh oblasts
      (regions) were similar with respect differentiation parameters, whereas the
      oblasts considerably differed from each other. At present, some Malecot's
      isolation-by-distance parameters for the populations of the districts that were
      included to Belgorod oblast in 1954 are lower and similar to those for the
      districts that remain in Kursk and Voronezh oblasts.

PMID- 19382692
TI  - [Regulation of ceruloplasmin gene activity in mammary gland cells].
AB  - Tissue-specific regulation of the expression of ceruloplasmin (CP) gene, which
      encodes major copper-containing extracellular glycoprotein was investigated. A
      decrease of the CP concentration associated with copper amounts in milk during
      the first 3 days of lactation was used as phenotypic index for evaluating the CP
      enzyme activity in the mammary gland. Computer analysis of mammalian CP gene
      promoter region has revealed conserved sequences of cis-elements, which
      potentially were capable of regulating the enzyme activity. It has been shown
      that changes in the nucleotide sequence of specific transcriptional factor
      binding sites located at 5'-end of CP gene were associated with disturbance of
      the regular downregulation of CP gene activity during lactation.

PMID- 19382693
TI  - [Polymorphism of pigmentation genes (OCA2 and ASIP) in some populations of
      Russia].
AB  - In Russian populations, polymorphism of two pigmentation system genes, OCA2 (loci
      305, 355, and 419, tested in Russians, Buryats, Chukchi, Koryaks, and Evens) and
      ASIP (locus 8818, tested in Russians and Buryats) was examined. Pairwise
      comparisons of the F(ST) distances between the populations showed that only the
      populations from Northeast Asia (Chukchi, Koryaks, and Evens) were statistically
      significantly different from all other populations, at least relative to one of
      the OCA2 locus. In Russians from Pskov oblast and Novgorod oblast, increased
      frequency (up to 6%) of the OCA2 allele 419A was revealed. In earlier studies, as
      association of this allele with green eye color was demonstrated. The data
      obtained in terms of their application for ethnic population genetics.

PMID- 19382694
TI  - [Analysis of Alu-insertion polymorphism in three subethnic groups of Kalmyks].
AB  - Eight Alu insertions at the NBC27, TPA25, NBC148, NBC123, ACE, APOA1, NBC51, and
      PV92 locus were examined in three subethnic groups of Kalmyks (Torgouds, Derbets,
      and Buzava). In general, the pattern of allele frequencies in Kalmyks was
      consistent with that in Asian populations of the world, and was similar to the
      Alu insertion frequencies pattern in Turkic populations of the Volga--Ural region
      and Central Asia. Pairwise comparisons of three subpopulations of Kalmyks with
      respect to the frequency distributions of eight Alu insertions revealed the
      differences between the groups examined. The coefficient of gene differentiation,
      F(st), constituted 1.37%, pointing to the common origin of the groups of
      interest, as well as to the uniformity of the gene pools of subethnic groups of
      Kalmyks examined.

PMID- 19382695
TI  - [Marriage migration parameters in six rural districts of Bashkortostan Republic].
AB  - The marriage migration structure of the populations of six districts of
      Bashkortostan Republic has been studied. The rates of assortative marriages in
      Bashkirs, Tatars, and Russians are 1.02-2.71, 1.30-5.99, and 2.14-7.50,
      respectively; the endogamy indices are 0.58-0.97, 0.90, and 0.68, respectively.
      Malecot's isolation-by-distance parameters in Bashkirs, Tatars, and Russians,
      respectively, are the following: sigma is 6.7-83.0, 40.3-106.1, and 69.9; a is
      0.00012-0.00074, 0.00170-0.0029, and 0.00096; and b is 0.0087-0.0467, 0.0038
      0.0208, and 0.0129. Changes in these parameters with time have been traced.

PMID- 19382696
TI  - [The Dagestan gene pool: interethnic and intraethnic differentiation of eight
      aboriginal ethnic groups: analysis based on data on the AB0 and Rhesus
      erythrocyte antigen systems].
AB  - Analysis of the genetic variation of eight aboriginal Dagestan ethnic groups
      based on data on the AB0 and Rhesus blood groups has been carried out in a total
      sample of 18 348 subjects. The degree of genetic differentiation (G(ST)) and the
      levels of intraethnic (H(S) and interethnic (H(T)) variations of Dagestan ethnic
      groups have been estimated at two hierarchical levels of the population system.
      Prevalence of intraethnic diversity over interethnic one has been found in
      Dagestan populations. The parameters of subdivision of Dagestan populations were
      compared with those for the populations of all other regions of the Caucasus and
      the Pamir. The population subdivision of ethnic groups of Dagestan and other
      regions of the Caucasus is lower than that of Pamir ethnic groups.

PMID- 19382697
TI  - [Genetic control of efficient leaf rust resistance in collection accessions of
      barley Hordeum vulgare L].
AB  - Leaf rust resistance was studied in barley accessions from the worldwide
      collection of the All-Russia Institute of Plant Industry. Most accessions
      described as highly resistant in the literature proved susceptible. High
      resistance at the juvenile stage was observed only for the cultivars Henry,
      Cebada Capa, Forrajera Klein, and Scarlet. Hybrid analysis and phytopathological
      tests showed that the cultivar Scarlet had one dominant resistance gene, Rph7.
      Adult resistance was demonstrated for accession NB-3002 from Nepal, which proved
      to have one dominant gene on evidence of hybrid analysis.

PMID- 19382698
TI  - [The microbial synthesis of flavin nucleotides: a review].
AB  - Recent data on the synthesis and hydrolysis of flavin nucleotides in yeast and
      bacteria and the regulation of this process are summarized. Specific examples are
      provided and the prospects of the use of genetically modified microorganisms for
      the industrial manufacturing of flavin mononucleotide and flavin dinucleotide are
      considered.

PMID- 19382699
TI  - [Catalytic activity and the stability of horseradish peroxidase increase as a
      result of its incorporation into a polyelectrolyte complex with chitosan].
AB  - The incorporation of horseradish peroxidase into polyelectrolyte complexes with
      chitosans of different molecular weights (MW 5-150 kDa) yielded highly active and
      stable enzyme preparations. As a result of the selection of optimal conditions
      for the formation of peroxidase-chitosan complexes, it was found that 0.1%
      chitosan with a MW of 10 kDa had the strongest activatory effect on peroxidase
      (activation degree, > 70%) in the reaction of o-dianisidine oxidation by hydrogen
      peroxide. The complex formed by 0.001% chitosan with a molecular weight of 150
      kDa was most stable: when immobilized on foamed polyurethane, it retained at
      least 50% of the initial activity for 550 days. The highest catalytic activity
      was exhibited in a 0.05 M phthalate buffer (pH 5.9-6.2) by the complex containing
      0.006-0.009% chitosan in the indicator reaction. The activatory effect of the
      polysaccharide on the enzyme was determined by its influence on the binding and
      conversion of the reducting substrate peroxidase.

PMID- 19382700
TI  - [Transglycosylation of benzo[h]quinazolines].
AB  - This was the first study to apply cyclodextrin glucanotransferases (CGTase, EC
      2.4.1.19) produced by mesophilic, thermophilic, alkaliphilic, and halophilic
      bacilli as well as pullulanase, beta-amylase, beta-galactosidase, and beta
      fructofuranosidase for transglycosylation of benzo[h]quinazolines. The
      combination of CGTase produced by Bacillus stearothermophilus ST-88 and gamma
      cyclodextrin (CD) used as a donor of glucosyl residues was the most efficient.
      The derivatives obtained are water-soluble. The synthesized products have been
      purified by various chromatographic methods and their fine structures have been
      determined.

PMID- 19382701
TI  - [The regulation of peroxisomal matrix enzymes (alcohol oxidase and catalase)
      formation by the product of the gene Mth1 in methylotrophic yeast Pichia
      methanolica].
AB  - Two independent mutant strains of methylotrophic yeast Pichia methanolica (mth1
      arg1 and mth2 arg4) from the initial line 616 (ade1 ade5) were investigated. The
      mutant strains possessed defects in genes MTH1 and MTH2 which resulted in the
      inability to assimilate methanol as a sole carbon source and the increased
      activity of alcohol oxidase (AO). The function of the AUG2 gene encoding one of
      the subunits of AO and CTA1, a probable homolog of peroxisomal catalase of
      Saccharomyces cereviseae, was investigated by analyses of the molecular forms of
      isoenzymes. It was shown that optimal conditions for the expression of the AUG2
      gene on a medium supplemented with 3% of methanol leads to an increasing
      synthesis of peroxisomal catalase. The mutant mth1 possessed a dominant formation
      of AO isoform with electrophoretic mobility which is typical for isogenic form 9,
      the product of the AUG2 gene, and a decreased level of peroxisomal catalase. The
      restoration of growth of four spontaneous revertants of the mutant mth1 (Rmth1)
      on the methanol containing medium was accompanied by an increase in activity of
      AO isogenic form 9 and peroxisomal catalase. The obtained results confirmed the
      functional continuity of the structural gene AUG2 in mutant mth1. The correlation
      of activity of peroxisomal catalase and AO isogenic form 1 in different
      conditions evidenced the existence of common regulatory elements for genes AUG2
      and CTA1 in methilotrophic yeast Pichia methanolica.

PMID- 19382702
TI  - [Cloning of the Penicillium canescens endo-1,4-beta-glucanase gene egl3 and the
      characterization of the recombinant enzyme].
AB  - The gene egl3 of the filamentous fungus Penicillium canescens endo-1,4-beta
      glucanase, belonging to family 12 glycosyl hydrolases, was cloned and sequenced.
      The gene was expressed in P. canescens under the control of the strong promoter
      of gene bgaS, coding for beta-galactosidase of this fungus, and efficient
      endoglucanase producer strains were obtained. The recombinant protein was
      isolated from the culture liquid of the producer strain EGL3-13 and purified to
      homogeneity; its specific activity was 31.7 IU; molecular weight, 26 kDa; and pH
      and temperature optimums, 3.2 and 54 degrees C, respectively. The Km and Vm
      values for CMC hydrolysis were determined; they amounted to 17.1 g/1 and 0.31
      microM/(mg s), respectively.

PMID- 19382703
TI  - Properties of two endoglucanases from a mutant strain Trichoderma sp. M7 with
      potential application in the paper industry.
AB  - Two endoglucanases were purified to electrophoretic homogeneity from the culture
      filtrate of a mutant strain Trichoderma sp. M7. EG-III and EG-IV had Mr of 49.7
      and 47.5 kDa, and estimated pI values of 3.7 and 6.35, respectively. The optimal
      pH and temperature values were determined to be pH 5.0 and 60 degrees C for the
      first cellulase, whereas pH 5.2 and 50 degrees C were optimal for the other.
      Endoglucanases exhibited typical Michaelis-Menten kinetics with Km and V values
      of 2.9 mg ml(-1) and 60498.5 micromol min(-1) mg(-1) for EG-III and 3.8 mg ml(-1)
      and 22650.9 micromol min(-1) mg(-1) for EG-IV, respectively. Mn2+, Cu2+ and Pd2+
      strongly inhibited the enzymes. EG-IV catalyzed the hydrolysis of Na-CMC and
      hydroxyethyl cellulose (HEC) only, whereas EG-III displayed high activity towards
      xylans, also. Different preferences towards cellulosic substrates and their
      regions define a different role of the investigated enzymes in the degradation of
      plant biomass.

PMID- 19382704
TI  - High-level secretory production of recombinant human platelet-derived growth
      factor--BB by Saccharomyces cerevisiae under the non-selective conditions.
AB  - Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) was produced by
      Saccharomyces cerevisiae. A two-stage cultivation strategy with mixture of
      glucose and galactose was developed to enhance rhPDGF-BB production, with its
      concentration being 32 mg/l fermentation broth under optimal conditions: corn
      steep powder as nitrogen source, 2 g/1 of glucose concentration at the beginning
      of induction phase, a pH of 5.0 and 6.5 for cell growth and rhPDGF-BB
      accumulation. The purification process consisted of yeast supernatant
      ultrafiltration followed by ion exchange chromatography and molecular sieve, and
      the recovery of rhPDGF-BB was estimated to be 20.28%. Biological activity of the
      purified rhPDGF-BB was 3.05 ng/ml.

PMID- 19382705
TI  - [Effect of a synthetic analogue of bacterial anabiosis autoinducers
      hexylresorcinol on the stability of membrane structures].
AB  - The effect of hexylresorcinol (HR), a chemical analogue of microbial anabiosis
      autoinducers of the alkylhydroxybenzene (AHB) group, on the stability of
      biological membranes and monolamellar liposomes formed of egg phosphatidylcholine
      (ePC) was studied. According to spectrophotometry and electron microscopy
      studying of HR-loaded liposomes in the presence of a surface-active agent Tween
      20, the critical ratio between HR and ePC for liposome preservation was found to
      be close to equimolar. The trends in HR influence on membrane structural
      organization and stability confirmed in experiments on liposomes were also
      reproduced on intact bacterial cells explaining non-species-specific effect of
      AHBs. The demonstrated high efficiency of AHB biocides may be used in material
      and equipment protection against biocorrosion.

PMID- 19382706
TI  - [Phenanthrene and anthracene degradation by microorganisms of the genus
      Rhodococcus].
AB  - The cells of Rhodococcus opacus 412 and R. rhodnii 135 were adapted to
      phenanthrene and anthracene on a solid mineral medium. Preliminary adaptation of
      the strains accelerated the metabolism of polyaromatic hydrocarbons and provided
      for the ability of microorganisms to grow on pheanthrene as a sole carbon and
      energy source in a liquid mineral medium. It was shown that phenanthrene was
      mineralized by the strains through 7,8-benzocoumarin, 1-hydroxy-2
      naphthoaldehyde, 1-hydroxy-2-naphthoic acid, salicylaldehyde, salicylate and
      catechol to the intermediates of tricarbonic acid cycle and partially transformed
      with the accumulation of the products of subsequent monooxygenation (3
      hydroxyphenanthrene and phenanthrene dihydroxylated not in ortho-position). As a
      result of the adaptation of the strains to anthracene on a solid mineral medium,
      the obtained variant of strain R. opacus 412 was able to transform anthracene in
      a liquid mineral medium to anthraquinone and 6,7-benzocoumarin.

PMID- 19382707
TI  - [Special traits of decomposition of azo dies by anaerobic microbial communities].
AB  - We present the results of an investigation into the special traits of conversion
      of azo dies golden yellow, acid orange, methyl orange, and methyl red under
      anaerobic conditions in comparison to aerobic conditions. In the presence of
      oxygen, only methyl red underwent decomposition, while under oxygen-free
      conditions, all remaining substances were fully discolored under the action of a
      methanogenous consortium of organisms. The products of reduction of the azo bond
      are determined in the case of each die. Introduction of additional acceptors of
      electrons (sulfate and nitrate) had a negative influence on the discoloration of
      azo dies. Addition of ethanol as an available organic cosubstrate accelerated
      decomposition of azo dies both under methanogenous and sulfate- and nitrate
      reducing conditions. There is no direct correlation between the rates of
      conversion of azo dies under anaerobic conditions or their toxicity to
      acetoclastic methanogens. Changes in the morphological composition of the
      community discoloring an azo die depended on the duration of its impact on
      microorganisms. The mechanism of the reduction of the azo bond under the action
      of substances acting as mediators is explained. These substances are products of
      the metabolism of the microbial community in anaerobic conditions. It is shown
      that the supposed mediators NADH and sulfide efficiently discolor azo dies in a
      cell-free system, while riboflavin significantly increased the rate of conversion
      of substrates in recurrent cycles of discoloration only in the presence of an
      anaerobic microbial consortium.

PMID- 19382708
TI  - [Clavine alkaloid biosynthesis by the fungus Penicillium palitans westling 1911
      isolated from ancient permafrost deposits].
AB  - The relic strain of Penicillium palitans isolated from the ancient permafrost
      deposits produces clavine alkaloids such as festuclavine, fumigaclavine A, and
      fumigaclavine B. Alkaloid biosynthesis is concurrent with the growth. Tryptophan
      and zinc ion additives to the culture medium stimulate the synthesis of
      alkaloids.

PMID- 19382709
TI  - [The composition of volatile components of cepe (Boletus edulis) and oyster
      mushrooms (Pleurotus ostreatus)].
AB  - The composition of aroma compounds in cooked and canned cepe (Boletus edulis) and
      in cooked oyster mushrooms (Pleurotus ostreatus) is studied using capillary gas
      chromatography and chromatography-mass spectrometry. It is found that unsaturated
      alcohols and ketones containing eight atoms of carbon determine the aroma of raw
      mushrooms and take part in the formation of the aroma of cooked mushrooms as
      well. The content of these compounds was the highest in canned cepes. In oyster
      mushrooms, the concentration of these alcohols and ketones was lower in
      comparison with cepes. The content of aliphatic and aromatic aldehydes was much
      higher in oyster mushrooms. Volatile aliphatic and heterocyclic Maillard reaction
      products and isomeric octenols and octenones formed the aroma of cooked and
      canned mushrooms.

PMID- 19382710
TI  - [Evaluation of the effect of late blight-resistant potato plants on the structure
      of bacterial associations in soil].
AB  - We studied the compositions of microbial associations isolated from soils where
      nontransgenic and transgenic late blight-resistant lines of potato varieties
      Lugovskoi, Charodei, and Golubizna had been grown. The analysis was based on
      denaturing gradient gel electrophoresis of total amplificates of 16S rRNA gene
      fragments and analysis of libraries of nifH gene fragments. Neither method
      revealed significant differences in the structure of the microbial associations
      isolated from soils with control or transgenic plants. The minor differences
      detected in the microflora ranges were no greater than those in the rhizospheres
      of different nontransgenic potato varieties.

PMID- 19382711
TI  - [Wound healing and induced resistance in potato tubers].
AB  - It was demonstrated that biogenic elicitors, arachidonic acid and chitosan,
      locally and systemically stimulated wound healing in potato tuber tissues by
      increasing the number of wound periderm layers, accelerating the development of
      cork cambium (phellogen), and inducing proteinase inhibitors. The signal
      molecules, jasmonic and salicylic acids, had different effects on the development
      of wound periderm: jasmonic acid locally and systemically stimulated potato wound
      healing and elevated the level of proteinase inhibitors, whereas salicylic acid
      did not have any effect on wound healing and even blocked the formation of
      proteinase inhibitors.

PMID- 19382712
TI  - [Development of immunochromatographic test systems for express detection of plant
      viruses].
AB  - Express immunochromatographic test-strip assays were developed for detection of
      five plant viruses varying in shape and size of virions: spherical carnation
      mottle virus, bean mild mosaic virus, rod-shaped tobacco mosaic virus, and
      filamentous potato viruses X and Y. Multimembrane composites (test strips) with
      immobilized polyclonal antibodies against viruses and colloidal gold-conjugated
      antibodies were used for the analysis. The immunochromatographic test strips were
      shown to enable the detection of viruses both in purified preparations and in
      leaf extracts of infected plants with a sensitivity from 0.08 to 0.5 microg/ml
      for 10 min. The test strips may be used for express diagnostics of plant virus
      diseases in field conditions.

PMID- 19382713
TI  - [Enzyme immunoassay for the determination of the glycopeptide antibiotic
      eremomycin].
AB  - An indirect competitive enzyme-linked immunosorbent assay (ELISA) was developed
      using rabbit polyclonal antibodies against the eremomycin-glucose oxidase
      conjugated antigen. This technique allows the glycopeptide antibiotic eremomycin
      to be determined both in aqueous solutions (with a sensitivity as high as 0.1
      ng/ml) and in blood plasma. The cross-reactivity of the antibodies with
      vancomycin was 0.4% of that for eremomycin, while teicoplanin was almost not
      recognized. Experiments with blood plasma samples diluted 1:10 showed that the
      assay was linear over the concentration range 1-30 ng/ml and that the variation
      coefficient did not exceed 10%. The high sensitivity and selectivity of this test
      make it suitable for pharmacokinetic studies and drug monitoring analysis.

PMID- 19382714
TI  - [Affine magnetic sorbents supported on coal ash microspheres for recombinant
      protein isolation].
AB  - The results of the development and utilization of an affine magnetic sorbent with
      Ni2+ ions immobilized on coal ash microspheres are reported. The applicability of
      the material in the isolation of Histag proteins is demonstrated by examples of
      the recombinant green fluorescent protein from Clytia gregarium and the Ca2+
      regulated photoprotein obelin from Obelia longissima. The specific sorption
      capacity of the sorbent was 2-7 mg/cm3 for medium-size proteins (20-30 kDa). The
      particles are suitable for chromatography with the presence of chaotropic agents
      and EDTA. They are easy to manipulate as isolation of a target protein takes 30
      35 min. On one hand, the elevated affinity of the sorbent to proteins rich in
      native histidines may result in a high degree of irreversible sorption; on the
      other hand, it allows isolation of such proteins without the introduction of
      artificial polyhistidine tracts.

PMID- 19382715
TI  - [Sorption of lysine by molecularly imprinted carboxyl sorbents].
AB  - Tuned (molecularly imprinted) and nontuned, with respect to lysine amino acid,
      carboxylic heteroreticular sorbents based on methacrylic acid and ethylene glycol
      dimethacrylate, were synthesized. Study of sorption of lysine within wide pH
      range and ionic strength indicated significant dissimilarities in amino acid
      sorption by tuned sorbents, which were expressed as an increase in the
      contribution of nonionic interaction, and resulted in a decrease in the ionic
      strength effect on the sorption capacity, as well as an increase in amino acid
      sorption selectivity.

PMID- 19382716
TI  - [Antimicrobial activity of carbon fiber fabric modified with a polymer-gentamicin
      complex].
AB  - Modified and unmodified carbon fiber supports were treated with solutions of a
      polymer-gentamicin complex, possessing high antimicrobial activity and low
      toxicity. It was found that the antimicrobial activity of modified carbon fiber
      fabrics depended on the nature of the support and on the immobilization
      conditions. The highest antimicrobial activity was observed with phosphorus
      containing carbon fiber ion exchanger in salt form.

PMID- 19382717
TI  - [Carbon nanotube-based biosensors for DNA structure characterization].
AB  - The possibility of DNA detection using electrodes modified with carbon nanotubes
      (CNTs) was studied. CNTs facilitate the electrochemical oxidation of DNA guanine
      nucleotide, which allows direct detection of DNA on a modified electrode.
      Electrochemical properties of DNA depend on its secondary structure and molecular
      weight. Denaturation of native DNA improves the adsorption of biopolymer on CNTs
      and results in an increase in DNA oxidation current on the modified electrode. A
      similar effect is observed after ultrasonic shearing of DNA or its treatment with
      Fenton's reagent due to the fragmentation of biopolymer. Our results demonstrate
      the feasibility of biosensors based on CNT-modified electrodes for the direct
      detection and characterization of DNA and DNA damaging factors.

PMID- 19382718
TI  - Migrating motor complex in biological sciences: characterization, animal models
      and disturbances.
AB  - The migrating motor complex (MMC) occurs in most mammals and birds and is
      organized during the fetal life. In some species, like ruminants and other
      herbivores, it is not abolished by feeding but its character and controlling
      mechanisms do not vary considerably from other animal species. However, the
      mechanisms controlling the MMC are complex and incompletely recognized. The
      central nervous system exerts rather modulatory effects upon the MMC and the role
      of the enteric nervous system in the initiation and propagation of the MMC is
      crucial. The hormones appear mainly to disrupt and convert the MMC cycle into the
      fed pattern. Several types of the disturbances of the MMC cycle and its phases
      have been described in various pathophysiological conditions. However, it can be
      more suitable to identify and describe the given MMC abnormality than to
      establish the rules of the MMC behavior in the course of the gastrointestinal
      diseases.

PMID- 19382719
TI  - Restriction enzyme analysis of VP7 gene of Indian isolates of bluetongue virus.
AB  - The genome segment 7 of two Indian isolates of bluetongue virus (BTV) from
      Avikanagar (BTV-1-western India) and Hyderabad (BTV-Untyped Hyderabad-southern
      India) was amplified by RT-PCR using two sets of VP7 specific primers. A sequence
      of 1137 bp comprising the complete coding sequence of the VP7 gene from
      Avikanagar isolate and a 1154 bp full-length sequence from BTV-UT Hyderabad
      isolate were amplified. Further, restriction enzyme digestion of these full
      length amplicons, using EcoRI, PstI and TaqI revealed that genome segment 7 from
      both isolates were different from each other by absence of any EcoRI site in the
      BTV-UT Hyderabad isolate. There were also variations in the number and position
      of restriction sites for TaqI enzyme in these two isolates. Taql has two sites in
      the Avikanagar isolate whereas four sites in BTV-UT Hyderabad. The restriction
      digestion fragments obtained after PstI digestion were differentiated on the
      basis of their distinct sizes in both isolates. Comparison of their in silico
      restriction profiles with that of other isolates from different countries
      revealed that the two Indian isolates belonging to different parts of India had
      variations in their VP7 gene which was also distinguishable from at least some
      isolates from Australia and South Africa. Hence the restriction enzyme (RE) based
      analysis might be a useful tool in determining the genetic diversity in genome
      segment 7 and also for tracing their evolutionary relationships.

PMID- 19382720
TI  - Isolation and identification of poly beta hydroxybutyric acid accumulating
      bacteria of Staphylococcal sp. and characterization of biodegradable polyester.
AB  - Staphylococcus sp. strain BP/SU1, capable of degrading the biopolymer and utilize
      it as a source of carbon and energy, was isolated from activated sludge using
      METABOLIX (MBX D411G). It was found that this strain was capable of accumulating
      poly(3-hydroxybutyric acid) P(3-HB), as granule poly (3-hydroxybutyric acid), p(3
      HB), inclusion bodies when grown under suitable nutrient conditions. These
      strains could sustain cell growth up to a dry mass of 9.24 g/l with a doubling
      time of 8 to 10 hr and could accumulate P(3-HB) as granular inclusion bodies to a
      cell dry weight of more than 12%. P(3-HB) accumulated by this organism was
      isolated and characterized through NMR, FT-IR spectroscopy, UV Spectroscopy, Mass
      spectroscopy and Differential Scanning Calorimetry. P(3-HB) granules so isolated
      showed physical and chemical properties that should be possessed by a superior
      quality thermoplastic biopolymer.

PMID- 19382721
TI  - Hepatoprotective activity of six polyherbal formulations in CCl4-induced liver
      toxicity in mice.
AB  - To evaluate pretreatment of six polyherbal liquid formulations (PLFs)
      commercially available in India, on CCl4-induced liver injury, Swiss albino mice
      were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body
      weight/day, po) followed by single sc injection of 50% (v/v) CCl4 in arachis oil
      at a dose of 1 ml/kg. The serum biochemical parameters such as alanine
      transaminases, aspartate transaminases and alkaline phosphatase were estimated.
      Phenobarbitone-induced sleeping time and liver histopathology were also carried
      out. CCl4-treated animals showed significant increase in the levels of liver
      enzymes, phenobarbitone-induced sleeping time and revealed fatty changes and
      centrizonal necrosis on histological examination of liver indicating hepatic
      damage. When pretreated with PLFs at a dose of 5.2 ml/kg body weight/day, the
      CCl4-induced changes were significantly reversed. The pretreatment with PLFs can
      prevent acute liver damage induced by CCl4 only at a higher dose. Therefore, it
      is suggested that a dose adjustment of these PLFs may be necessary for their
      optimal effects in human liver diseases.

PMID- 19382722
TI  - Protective effects of propolis on inorganic mercury induced oxidative stress in
      mice.
AB  - Protective potential of propolis was evaluated against mercury induced oxidative
      stress and antioxidant enzymatic alterations in mice liver. Exposure to mercuric
      chloride (HgCl2; 5 mg/kg; ip) induced oxidative stress by increasing lipid
      peroxidation and oxidized glutathione level along with concomitant decrease in
      glutathione and various antioxidant enzymes. Mercury intoxication deviated the
      activity of liver marker enzymes in serum. Conjoint treatment of propolis (200
      mg/kg; po) inhibited lipid peroxidation and oxidized glutathione level, whereas
      increased glutathione level. Activities of antioxidants enzymes, i.e., superoxide
      dismutase, catalase, glutathione-S-transferase and glucose-6-phosphate
      dehydrogenase were also restored concomitantly towards control after propolis
      administration. Release of serum transaminases, alkaline phosphatase, lactate
      dehydrogenase and y-glutamyl transpeptidase were significantly restored towards
      control after propolis treatment. Results suggest that propolis augments the
      antioxidants defense against mercury induced toxicity and provides evidence that
      it has therapeutic potential as hepatoprotective agent.

PMID- 19382723
TI  - Antidiabetic and antioxidant activity of Terminalia belerica. Roxb.
AB  - Effect of continuous administration of dried 75% methanolic extract of fruits of
      Terminalia belerica (Combretaceae) suspended in water was studied in alloxan
      induced hyperglycemia and antioxidant defense mechanism in rats. T. belerica
      prevented alloxan-induced hyperglycaemia significantly from 6th day of
      administration and there was 54% reduction on 12th day. Oxidative stress produced
      by alloxan was found to be significantly lowered by the administration of T.
      belerica extract. This was evident from a significant decrease in thiobarbituric
      acid reactive substances, conjugated dienes and hydroperoxides in blood and liver
      respectively. Similarly, decreased glutathione level produced by alloxan was
      increased by the administration of the extract in blood and liver. However the
      increase was not significant. Superoxide dismutase which was decreased by alloxan
      was significantly increased from 9th day in blood and liver of drug treated
      group. Similarly there was significant increase in the activity of catalase in
      blood and liver. Decrease in glutathione peroxidase by alloxan administration was
      found to be increased significantly in the blood and liver from 9th day by
      extract treatment. Glutathione reductase also was found to be increased in blood
      and liver. These results suggested that T. belerica fruit extract possessed anti
      diabetic and anti-oxidant activity and these activities may be interrelated.

PMID- 19382725
TI  - Effect of aqueous extract of Bulbine natalensis Baker stem on haematological and
      serum lipid profile of male Wistar rats.
AB  - Bulbine natalensis stem extract (25, 50 and 100 mg/kg body weight for 14 days)
      did not significantly alter the red blood cell count, haemoglobin, packed cell
      volume, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular
      haemoglobin concentration and red cell distribution width in male Wistar rats. In
      contrast, the white blood cell count increased by the end of the experimental
      period. While the levels of neutrophils, lymphocytes and eosinophils decreased
      after the administration of single dose of the extract (day 1), those of the
      platelets and monocytes increased. The extract also reduced the levels of
      basophils and large unstained cells after the seven daily doses. All the doses
      increased the serum concentrations of cholesterol and triacylglycerols. Whereas
      the serum concentration of low-density lipoprotein was unaffected throughout the
      experimental period, the decrease in high-density lipoprotein cholesterol was
      accompanied by increase in the atherogenic index. The results showed that aqueous
      extract of B. natalensis stem exhibited localized systemic toxicity mainly on the
      white blood cell count and related indices. The alterations in the serum lipid
      profile may predispose the animals to atherosclerosis especially when consumed
      repeatedly for two weeks.

PMID- 19382724
TI  - Antioxidant and antihyperlipidemic activity of Hibiscus sabdariffa Linn. leaves
      and calyces extracts in rats.
AB  - Antioxidant and antihyperlipidemic activities of the extracts of leaves and
      calyces of Hibiscus sabdariffa were investigated by studying their in vitro
      inhibitory activity on lipid peroxidation and in vivo effects on cholesterol
      induced hyperlipidemia. Highest antioxidant activity was exhibited by ethanolic
      extract of calyces followed by ethanolic extract of leaves followed by aqueous
      extract of leaves of H. sabdariffa. In cholesterol induced hyperlipidemic model,
      groups of rats treated with extracts of calyces and leaves of H. sabdariffa
      showed a significant decrease in the serum TC, LDL-C, VLDL-C, TAG values
      alongwith an increase in serum HDL-C levels. The treated groups also showed
      significant decrease in the atherogenic index, LDL-C: HDL-C risk ratios, and in
      the levels of SGOT, SGPT and ALP activities compared to cholesterol induced
      hyperlipidemic control group. Significant antihyperlipidemic activity was shown
      by ethanolic extract of calyces, followed by ethanolic extract of leaves. It was
      observed from the histopathological findings that rats fed with H. sabdariffa
      extracts showed decrease in granular degeneration caused by cholesterol feedings.
      Results suggest that the ethanolic extracts of calyces and leaves of H. sabdarifa
      containing polyphenols and flavanols possess significant antioxidant and
      antihyperlipidemic activities.

PMID- 19382726
TI  - In vitro synthesis of Frankia and mycorrhiza with Casuarina equisetifolia and
      ultrastructure of root system.
AB  - Casuarina equisetifolia is one of the ecologically and economically important
      tropical coastal trees nodulated by nitrogen-fixing actinomycete Frankia and
      forming symbiotic associations with both ecto- and endomycorrhizal fungi. The
      present study aims at the ultrastructural study of interactions between C.
      equisetifolia, Frankia, and mycorrhiza. C. equisetifolia seeds were sterilised
      and germinated under in vitro condition. The seedlings were transferred to
      conical flasks containing vermiculite and saw dust with Hoagland's solution.
      After 30 days, the inoculum of AM fungus--Glomusfasciculatum (A), ectomycorrhizal
      fungus-Pisolithus tinctorius (E) and actinorhizal Frankia (F) were inoculated
      individually and in various combinations, (A+E), (A+F), E+F) and (A+E+F). After
      90 days, the experimental plant roots and nodules were harvested for assessment
      of growth characters of mycorrhizal and actinorhizal association by light and
      scanning electron microscope methods. C. equisetifolia roots were infected with
      arbuscles and vesicles of G. fasciculatum; P. tinctorius formed fungal sheath but
      no Hartig net. Large number of cortical cells were seen infected with Frankia,
      hyphae of Frankia were frequently seen penetrating from cell to cell directly
      through cell walls and Frankia occupied majority of the cell volume.

PMID- 19382727
TI  - Antimicrobial activities of microbial strains isolated from soil of stressed
      ecological niches of Eastern Uttar Pradesh, India.
AB  - Antimicrobial activities of twenty bacterial strains isolated from ten different
      stressed agro-ecological niches of Eastern Uttar Pradesh, India were evaluated
      against bacteria, yeasts and molds. Eleven isolates showing strong antimicrobial
      activities were characterized. Eight antifungal compounds were purified and
      partially characterized by Ultra-Violet (UV) absorption spectra and grouped into
      polyenes and non-polyenes. Antibacterial metabolites produced by four isolates
      were purified and chemically characterized, of which one isolate (AB) produced a
      new form of olivanic acid, and other three isolates (C5, Py and M4) produced
      antibacterial compounds having phenoxazone nucleus.

PMID- 19382728
TI  - The HIPAA security rule--more questions than answers.

PMID- 19382729
TI  - The optimal RTLS solution for hospitals.

PMID- 19382730
TI  - The perfect economic storm. What's a CIO to do?

PMID- 19382731
TI  - Technology and nursing--a love/hate relationship.

PMID- 19382732
TI  - The care and feeding of clinical information systems. Challenges in IT
      enhancements and functionality.

PMID- 19382734
TI  - Safe harbor--addressing security issues in IT contracts.

PMID- 19382733
TI  - Across the pond. A European perspective on the contribution of IT to healthcare
      in the United States and the European community.

PMID- 19382735
TI  - Transforming EMRs--from patient snapshot to 'clinical hologram'.

PMID- 19382736
TI  - Lessons learned: mobile device encryption in the academic medical center.
AB  - The academic medical center is faced with the unique challenge of meeting the
      multi-faceted needs of both a modern healthcare organization and an academic
      institution, The need for security to protect patient information must be
      balanced by the academic freedoms expected in the college setting. The Albany
      Medical Center, consisting of the Albany Medical College and the Albany Medical
      Center Hospital, was challenged with implementing a solution that would preserve
      the availability, integrity and confidentiality of business, patient and research
      data stored on mobile devices. To solve this problem, Albany Medical Center
      implemented a mobile encryption suite across the enterprise. Such an
      implementation comes with complexities, from performance across multiple
      generations of computers and operating systems, to diversity of application use
      mode and end user adoption, all of which requires thoughtful policy and standards
      creation, understanding of regulations, and a willingness and ability to work
      through such diverse needs.

PMID- 19382737
TI  - Crying wolf: Consumers may be more willing to share medication information than
      policymakers think.
AB  - Current health IT policy directions assume lay people want to make explicit
      choices about who can access elements of their health information. To test this
      assumption, we presented lay people (N=31) with a decision scenario that required
      them to choose whether to share their medication information with three different
      types of physicians. Participants generally chose to share all of their
      medication information, citing anticipated clinical care benefits as the main
      reason for their choices. They seemed, however, unaware of the possible
      consequences of their choices.

PMID- 19382738
TI  - The next step in health data exchanges: trust and privacy in exchange networks.
AB  - The rapid development of health information exchanges (HIE), regional health
      information organizations (RHIO), the Nationwide Health Information Network
      (NHIN) and other data exchange platforms for health records creates complex and
      multifaceted challenges for protecting the privacy and security of health
      information. Often these issues are addressed in a contractual agreement between
      two parties seeking to exchange data. Until recently, this point-to-point
      approach has been acceptable because there were few operational HIEs or RHIOs
      that were ready, willing and able to actually exchange data. With the
      proliferation of HIEs and RHIOs that are either operational or on the cusp of
      being operational, the utility of point-to-point is diminishing. It is no longer
      efficient for a RHIO to negotiate a separate data exchange agreement with every
      one of its exchange partners. The evolving model for data exchange agreements is
      a multi-party trust agreement. This article will examine the crucial components
      of a multi-party trust agreement.

PMID- 19382739
TI  - Privacy and security in Pennsylvania: ensuring privacy and security of health
      information exchange in Pennsylvania.
AB  - Though HIPAA addresses privacy and security on a nationwide basis, state laws and
      regulations vary. This paper describes the landscape for privacy and security in
      Pennsylvania and its key elements. It addresses common myths and
      misunderstandings and provides an overview of what is actually required to
      provide needed protections privacy policies from government and the stakeholders;
      risk analysis and management; and technical and non-technical means to enforce
      policies and mitigate risks. Also covered are the enablers, barriers and key
      recommendations for the future.

PMID- 19382740
TI  - Best of breed strategies--hospital characteristics associated with organizational
      HIT strategy.
AB  - We identify the frequency at which various IT management strategies (e.g., best
      of breed, best of suite, or singlevendor solutions) are pursued in U.S.
      hospitals. We also examine hospital characteristics that are associated with
      pursuing one strategy over another. After combining several secondary data
      sources, 3343 hospitals were analyzed. Of these, 61 percent indicated a single
      vendor; 29 percent indicated a best-of-suite; and 10 percent suggested a best-of
      breed strategy. In multivariate models, single-vendor strategies were most common
      among hospitals that were small, stand-alone, for-profit, non-teaching and/or non
      JCAI accredited. Best of breed strategies were most common among system
      affiliated and JCAHO accredited hospitals; and best-of-suite IT strategies were
      most common among very large, system affiliated, teaching and JCAHO-acccredited
      hospitals. These findings enable hospital leaders to compare strategies with
      their peers. Moreover, IT vendors can identify the types of hospitals that would
      most likely benefit from their products or services.

PMID- 19382741
TI  - Optimizing the business and IT relationship--a structured approach to
      implementing a business relationship management framework.
AB  - The relationship between the business and the IT organization is an area where
      many healthcare providers experience challenges. IT is often perceived as a
      service provider rather than a partner in delivering quality patient care.
      Organizations are finding that building a stronger partnership between business
      and IT leads to increased understanding and appreciation of the technology,
      process changes and services that can enhance the delivery of care and maximize
      organizational success. This article will provide a detailed description of
      valuable techniques for optimizing the healthcare organization's business and IT
      relationship; considerations on how to implement those techniques; and a
      description of the key benefits an organization should realize. Using a case
      study of a healthcare provider that leveraged these techniques, the article will
      show how an organization can promote this paradigm shift and create a tighter
      integration between the business and IT.

PMID- 19382742
TI  - Nurses' knowledge of ILO recommendations for nursing service.

PMID- 19382743
TI  - Occupational health nursing: a two-fold challenge.

PMID- 19382744
TI  - Hydrogen bonding, electrostatic potential, and molecular design.
AB  - The V(alpha)(r) descriptor was introduced and shown to be an effective and useful
      predictor of hydrogen bond acidity. V(alpha)(r) is defined as the electrostatic
      potential at a distance, r, from the donor hydrogen on an axis defined by the
      nuclei of the hydrogen atom and the atom to which it is bonded. V(alpha)(r) is
      most predictive of hydrogen bond acidity for r = 0.55 A which is less than half
      the van der Waals radius of hydrogen. Calculated values of V(alpha)(r) and
      minimized electrostatic potential (V(min)) were used to show how molecular
      electrostatic potential can be used to provide insight into a number of hydrogen
      bonding phenomena, including lactam self-association, DNA base pairing, and
      bioisosterism. The effects of hydrogen bond formation on the strengths of other
      donors in the interacting molecules were explored and quantified. Implications of
      these results for modeling hydrogen bond acidity, derivation of atomic charges,
      and development of polarizable force fields were discussed.

PMID- 19382745
TI  - The cataract-associated R14C mutant of human gamma D-crystallin shows a variety
      of intermolecular disulfide cross-links: a Raman spectroscopic study.
AB  - The Arg14 to Cys (R14C) mutation in the human gammaD-crystallin (HGD) gene has
      been associated with a juvenile-onset hereditary cataract. We showed previously
      [Pande, A., et al. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 1993-1998] that rapid
      oxidation of Cys14 in the mutant leads to the formation of intermolecular,
      disulfide-cross-linked aggregates at physiological pH. Here we present a Raman
      spectroscopic analysis of R14C and HGD and show that R14C forms such aggregates
      even at pH 4.5. The lower pH enabled us to monitor the evolution of a variety of
      disulfide cross-links with distinct conformations around the CC-SS-CC dihedral
      angles. At least three cysteine residues are involved, forming protein-protein
      cross-links through disulfide-exchange reactions. From the pattern of the S-S and
      Trp Raman bands, we infer that Cys32 is likely to be involved in the cross
      linking. The data suggest that protein precipitation in the mutant may not be the
      direct result of disulfide cross-linking, although such cross-linking is the
      initiating event. Thus, our Raman data not only enhance the understanding of the
      reactivity of Cys14 in the R14C mutant and the mechanism of opacity, but also
      shed light on the mechanism of oxidative degradation during long-term storage of
      thiol-containing pharmaceuticals.

PMID- 19382746
TI  - Binding regions of outer membrane protein A in complexes with the periplasmic
      chaperone Skp. A site-directed fluorescence study.
AB  - Periplasmic Skp facilitates folding and membrane insertion of many outer membrane
      proteins (OMPs) into the outer membrane of Gram-negative bacteria. We have
      examined the binding sites of outer membrane protein A (OmpA) from Escherichia
      coli in its complexes with the membrane protein chaperone Skp and with Skp and
      lipopolysaccharide (LPS) by site-directed fluorescence spectroscopy. Single-Trp
      OmpA mutants, W(n)-OmpA, with tryptophan at position n in the polypeptide chain
      were isolated in the unfolded form in 8 M urea. In five beta(x)W(n)-OmpA mutants,
      the tryptophan was located in beta-strand x, in four l(y)W(n)-OmpA mutants, in
      outer loop y, and in three t(z)W(n)-OmpA mutants in turn z of the beta-barrel
      transmembrane domain (TMD) of OmpA. PDW(286)-OmpA contained tryptophan in the
      periplasmic domain (PD). After dilution of the denaturant urea in aqueous
      solution, spectra indicated a more hydrophobic environment of the tryptophans in
      beta(x)W(n) mutants in comparison to l(y)W(n)-OmpA and t(z)W(n)-OmpA, indicating
      that the loops and turns form the surface of hydrophobically collapsed OmpA,
      while the strand regions are less exposed to water. Addition of Skp increased the
      fluorescence of all OmpA mutants except PDW(286)-OmpA, demonstrating binding of
      Skp to the entire beta-barrel domain but not to the PD of OmpA. Skp bound the TMD
      of OmpA asymmetrically, displaying much stronger interactions with strands
      beta(1) to beta(3) in the N-terminus than with strands beta(5) to beta(7) in the
      C-terminus. This asymmetry was not observed for the outer loops and the
      periplasmic turns of the TMD of OmpA. The fluorescence results demonstrated that
      all turns and loops l(1), l(2), and l(4) were as strongly bound to Skp as the N
      terminal beta-strands. Addition of five negatively charged LPS per one preformed
      Skp.W(n)-OmpA complex released the C-terminal loops l(2), l(3), and l(4) of the
      TMD of OmpA from the complex, while its periplasmic turn regions remained bound
      to Skp. Our results demonstrate that interactions of Skp.OmpA complexes with LPS
      change the conformation of OmpA in the Skp complex for facilitated insertion and
      folding into membranes.

PMID- 19382748
TI  - MALDI-TOF MS reveals the molecular level structures of different hydrophilic
      hydrophobic polyether-esters.
AB  - Multi- and triblock copolymers based on 1,5-dioxepan-2-one/epsilon-caprolactone
      (DXO/CL) were investigated by MALDI-TOF MS to determine the influence of
      copolymer composition and architecture on the molecular structures at the
      individual chain level. The copolymer compositions, average block lengths, and
      molecular weights were determined by (1)H and (13)C NMR and by SEC, respectively.
      The structures of polyether-ester oligomers (linear, cyclic) as well as the
      chemical structures of their end groups were established on the basis of their
      MALDI-TOF mass spectra. The mass spectrum of PDXO homopolymer was relatively
      simple, however, complex mass spectra were obtained in the case of multi- and
      triblock copolymers and the mass spectra clearly discerned the molecular level
      effect of copolymer composition and copolymer type.

PMID- 19382747
TI  - Bimolecular fluorescence complementation demonstrates that the c-Fes protein
      tyrosine kinase forms constitutive oligomers in living cells.
AB  - The c-fes proto-oncogene encodes a unique nonreceptor protein-tyrosine kinase (c
      Fes) that contributes to the differentiation of myeloid hematopoietic, vascular
      endothelial, and some neuronal cell types. Although originally identified as the
      normal cellular homologue of the oncoproteins encoded by avian and feline
      transforming retroviruses, c-Fes has recently been implicated as a tumor
      suppressor in breast and colonic epithelial cells. Structurally, c-Fes consists
      of a unique N-terminal region harboring an FCH domain, two coiled-coil motifs, a
      central SH2 domain, and a C-terminal kinase domain. In living cells, c-Fes kinase
      activity is tightly regulated by a mechanism that remains unclear. Previous
      studies have established that c-Fes forms high molecular weight oligomers in
      vitro, suggesting that the dual coiled-coil motifs may regulate the
      interconversion of inactive monomeric and active oligomeric states. Here we show
      for the first time that c-Fes forms oligomers in live cells independently of its
      activation status using a YFP bimolecular fluorescence complementation assay. We
      also demonstrate that both N-terminal coiled-coil regions are essential for c-Fes
      oligomerization in transfected COS-7 cells as well as HCT 116 colorectal cancer
      and K-562 myeloid leukemia cell lines. Together, these data provide the first
      evidence that c-Fes, unlike c-Src, c-Abl, and other nonreceptor tyrosine kinases,
      is constitutively oligomeric in both its repressed and active states. This
      finding suggests that conformational changes, rather than oligomerization, may
      govern its kinase activity in vivo.

PMID- 19382750
TI  - X-ray diffraction, crystal structure, and spectral features of the optical
      susceptibilities of single crystals of the ternary borate oxide lead bismuth
      tetraoxide, PbBiBO4.
AB  - The all-electron full-potential linearized augmented plane-wave method has been
      used for an ab initio theoretical study of the band structure, the spectral
      features of the optical susceptibilities, the density of states, and the electron
      charge density for PbBiBO4. Our calculations show that the valence-band maximum
      (VBM) and conduction-band minimum (CBM) are located at the center of the
      Brillouin zone, resulting in a direct energy gap of about 3.2 eV. We have
      synthesized the PbBiBO4 crystal by employing a conventional solid-state reaction
      method. The theoretical calculations in this work are based on the structure
      built from our measured atomic parameters. We should emphasize that the observed
      experimental X-ray diffraction (XRD) pattern is in good agreement with the
      theoretical one, confirming that our structural model is valid. Our calculated
      bond lengths show excellent agreement with the experimental data. This agreement
      is attributed to our use of full-potential calculations. The spectral features of
      the optical susceptibilities show a small positive uniaxial anisotropy.

PMID- 19382751
TI  - Consistent van der Waals radii for the whole main group.
AB  - Atomic radii are not precisely defined but are nevertheless widely used
      parameters in modeling and understanding molecular structure and interactions.
      The van der Waals radii determined by Bondi from molecular crystals and data for
      gases are the most widely used values, but Bondi recommended radius values for
      only 28 of the 44 main-group elements in the periodic table. In the present
      Article, we present atomic radii for the other 16; these new radii were
      determined in a way designed to be compatible with Bondi's scale. The method
      chosen is a set of two-parameter correlations of Bondi's radii with repulsive
      wall distances calculated by relativistic coupled-cluster electronic structure
      calculations. The newly determined radii (in A) are Be, 1.53; B, 1.92; Al, 1.84;
      Ca, 2.31; Ge, 2.11; Rb, 3.03; Sr, 2.49; Sb, 2.06; Cs, 3.43; Ba, 2.68; Bi, 2.07;
      Po, 1.97; At, 2.02; Rn, 2.20; Fr, 3.48; and Ra, 2.83.

PMID- 19382752
TI  - Selective nanomolar detection of dopamine using a boron-doped diamond electrode
      modified with an electropolymerized sulfobutylether-beta-cyclodextrin-doped
      poly(N-acetyltyramine) and polypyrrole composite film.
AB  - N-acetyltyramine was synthesized and electropolymerized together with a
      negatively charged sulfobutylether-beta-cyclodextrin on a boron-doped diamond
      (BDD) electrode followed by the electropolymerization of pyrrole to form a stable
      and permselective film for selective dopamine detection. The selectivity and
      sensitivity of the formed layer-by-layer film was governed by the sequence of
      deposition and the applied potential. Raman results showed a decrease in the peak
      intensity at 1329 cm(-1) (sp(3)), the main feature of BDD, upon each
      electrodeposition step. Such a decrease was correlated well with the change of
      the charge-transfer resistance derived from impedance data, i.e., reflecting the
      formation of the layer-by-layer film. The polycrystalline BDD surface became more
      even with lower surface roughness as revealed by scanning electron and atomic
      force microscopy. The modified BDD electrode exhibited rapid response to dopamine
      within 1.5-2 s and a low detection limit of 4-5 nM with excellent
      reproducibility. Electroactive interferences caused by 4-dihydroxyphenylalanine,
      3,4-dihydroxyphenylacetic acid, ascorbic acid, and uric acid were completely
      eliminated, whereas the signal response of epinephrine and norepinephrine was
      significantly suppressed by the permselective film.

PMID- 19382753
TI  - Generation and limitations of peak capacity in online two-dimensional liquid
      chromatography.
AB  - The different operating conditions of an online two-dimensional liquid
      chromatographic separation (2D-LC), such as the length of the column, the linear
      velocity and the composition of the mobile phase used in the second dimension,
      its initial organic content if this separation is carried out in gradient
      elution, the number of fractions of the first column eluent collected, and the
      analysis time of the first dimension all affect the achievable separation power
      of 2D-LC online systems. The influences of these factors on the separation
      performance were investigated, and an equation was derived for the calculation of
      the achievable peak capacity in online 2D-LC assuming (1) that the option of
      undersampling the first-dimension separation is acceptable, (2) that the solutes
      follow linear-solvent-strength behavior, and (3) that all the separations are
      made in gradient elution. This theoretical discussion shows that (1) highly
      efficient separations made with online 2D-LC require the second-dimension peaks
      to be very narrow, (2) the separation power of 2D-LC systems is maximum for an
      optimum number of fractions collected in the first dimension, (3) higher peak
      capacities can be achieved by using shorter second-dimension columns and
      collecting a relatively large number of fractions, (4) the achievable 2D peak
      capacity is maximum for a certain eluent flow rate and column length of the
      second-dimension column, and (5) the maximum achievable peak capacity increases
      with decreasing velocity and initial organic content of the second-dimension
      eluent. As a consequence, due to the time restriction of the second-dimension
      gradient time, online 2D-LC schemes cannot realistically afford peak capacities
      exceeding 10,000, even if they are implemented with exceptionally efficient
      columns and if long analysis times are accepted.

PMID- 19382755
TI  - Analysis of semivolatile pharmaceuticals and pollutants in organic micro extracts
      using hot cell membrane inlet mass spectrometry.
AB  - This paper presents the first membrane inlet method that can be used together
      with field portable mass spectrometers for the analysis of semivolatile
      pharmaceuticals (pethidine, benzophenone, and cocaine) and environmental
      pollutants (terbutryne and butylated hydroxyl toluene (BHT)) dissolved in organic
      micro extracts. A microliter of the organic extract is simply injected into a
      closed hot cell membrane inlet (hc-MIMS), and an electron ionization mass
      spectrum of the vaporized semivolatile sample molecules can be recorded shortly
      thereafter. Detection limits at low picomole quantities or low/sub ng/microL
      concentrations in the extract are demonstrated for solutes in methanol, ethanol,
      acetone, and toluene. A linear correlation between analyte concentration and
      signal was found in the range of 1-100 ng/microL, and the relative standard
      deviation (RSD) was approximately 10%. As a practical example we demonstrate the
      detection of cocaine in extracts from dried coca leaves. The analysis of organic
      micro extracts using hc-MIMS represents a considerable extension of the type and
      complexity of analytes that can be measured using a field portable MIMS system,
      since it does not require special and field tedious modifications to the standard
      MIMS system.

PMID- 19382754
TI  - Hard top soft bottom microfluidic devices for cell culture and chemical analysis.
AB  - We report fabrication and characterization of microfluidic devices made of
      thermoplastic and elastomeric polymers. These hard-soft hybrid material devices
      are motivated by the combined need for large scale manufacturability, enhanced
      barrier properties to gas permeation and evaporation of aqueous solutions
      compared to poly(dimethyl siloxane) (PDMS) devices, and compatibility with
      deformation-based actuation. Channel features are created on rigid polymers such
      as polyethylene terephthalate glycol (PETG), cyclic olefin copolymer (COC), and
      polystyrene (PS) by hot embossing. These "hard tops" are bonded to elastomeric
      "soft bottoms" (polyurethane (PU) or PDMS-parylene C-PDMS) to create devices that
      can be used for microfluidic cell culture where deformation-based fluid actuation
      schemes are used to perfuse and recirculate media. The higher barrier properties
      of this device compared to PDMS devices enable cell culture with less evaporation
      and creation of hypoxic conditions.

PMID- 19382756
TI  - Copper-catalyzed synthesis of benzoxazoles via a regioselective C-H
      functionalization/C-O bond formation under an air atmosphere.
AB  - An efficient method for the synthesis of functionalized benzoxazoles is described
      that involves a copper(II)-catalyzed regioselective C-H functionalization/C-O
      bond formation protocol. The use of dichlorobenzene as a solvent at 160 degrees C
      allows the use of air as the terminal oxidant in the catalytic synthesis of
      benzoxazoles in a process that has high functional group tolerance. The presence
      of a directing group at the meta position markedly improves the reaction efficacy
      and a variety of 7-substituted benzoxazoles are selectively produced under mild
      reaction conditions. The mechanism of the reaction is also discussed in this
      report.

PMID- 19382757
TI  - One-pot multicomponent synthesis of 1-aryl-5-methyl-N-R2-1H-1,2,3-triazole-4
      carboxamides: an easy procedure for combinatorial chemistry.
AB  - A convenient synthetic protocol was elaborated for creation of combinatorial
      libraries of 1-(R(1)-phenyl)-5-methyl-N-R(2)-1H-1,2,3-triazole-4-carboxamides. As
      starting materials, commercially available or readily prepared azides, amines,
      and diketene were selected for the reaction which has proceeded in a one-pot
      system with high yields and in short time.

PMID- 19382758
TI  - Proteomic and bioinformatic analysis on endocrine organs of domesticated
      silkworm, Bombyx mori L. for a comprehensive understanding of their roles and
      relations.
AB  - Three organs of silkworm larva endocrine system, including brain (Br),
      subesophageal ganglion (SG) and prothoracic glands (PG), were studied employing
      shotgun LC-MS/MS combined with bioinformatic analysis to comprehensively
      understand their roles and relations. Totally, 3430, 2683, and 3395 proteins were
      identified including 1885 common and 652, 253, and 790 organ-specific ones in Br,
      SG, and PG, respectively. Identified common-expressed proteins indicated the
      existence of intrinsic complex interactions among these parts of endocrine
      system. Most of the reputed organs-specific proteins were identified by this
      approach. KEGG pathway analysis showed 162 same pathways among the 169, 164, and
      171 relating Br, SG, and PG. This analysis revealed functional similarities with
      exceptional resemblance in their metabolism and signaling pathways of the three
      organs. On the other hand, 70, 57, and 114 organ-specific enzymes related
      pathways were detected for Br, SG, and PG confirming their functional
      differences. These results reveal a cooperative mechanism among the three
      endocrine organs in regulating various physiological and developmental events,
      and also suggest that the organ-specific proteins might be the fundamental
      factors responsible for the functional differentiation of these organs.

PMID- 19382759
TI  - Molecular Co(III)/Fe(II) cyano-bridged mixed-valence compounds with high
      nuclearities and diversity of Co(III) coordination environments: preparative and
      mechanistic aspects.
AB  - The kinetico-mechanistic study of the formation of discrete tri- and tetranuclear
      mixed-valence cyano-bridged (Co(III))(2)/Fe(II) and (Co(III))(3)/Fe(II) complexes
      has been carried out from their already described parent dinuclear Co(III)/Fe(II)
      and mononuclear Co(III) complexes. Different Co(III) encapsulating units have
      been used in order to tune both the redox potential on the mono- and dinuclear
      complexes and the lability of the mononuclear building blocks. The importance of
      outer-sphere precursor complex formation involving the oppositely charged
      reactants has been established by experiments conducted at high ionic strength
      where electrostatic effects are nullified. The influence of the pH is also
      crucial, and this has been linked to the pH dependence of the precursor
      Co(III/)(II) redox potentials in terms of enabling a redox-assisted association
      (at low pH) between the ferricyanide analogue and the labile Co(II) partner. A
      new asymmetric Co(III)L/Fe(II)/Co(III)L' complex has been fully characterized,
      and a series of putative (Co(III)L)(2)/Fe(II)/Co(III)L' and (Co(III)L)(3)/Fe(II)
      forms have been spectroscopically detected. A comparison with the mechanistic
      reaction pathways established for the formation of the parent dinuclear
      Co(III)/Fe(II) complexes indicates that an important tuning of the direct
      substitution and redox-catalyzed mechanism is applicable. For the formation of
      the trinuclear complexes, only in the most favorable conditions is a redox
      assisted sequence observed. The rate and activation parameters for the reactions
      have been determined and are indicative of an essential outer-sphere precursor
      formation. Similarly, for reactions where redox-assisted mechanisms are
      unfavorable, only direct substitution processes have been found to be applicable,
      with their rate coefficients and activation parameters also agreeing with the
      expectations, once an outer-sphere precursor complex is formed. Formation of the
      tetranuclear (Co(III)L)(3)/Fe(II) complexes has only been detected on
      decomposition of the parent trinuclear (Co(III)L)(2)/Fe(II) complexes following
      reduction to their Co(II) form. The overall processes seem to be based on the
      outer-sphere association between the respective building blocks in such a way
      that both unfavorable redox potentials and Lewis basicities are overcome.

PMID- 19382760
TI  - Copper phthalate coordination polymers incorporating kinked dipyridyl ligands: an
      unprecedented 8-connected network and one-dimensional chiral nanobarrels with
      hydrophobic channels constructed from septuple helical motifs.
AB  - Copper phthalate coordination polymers incorporating the kinked and hydrogen
      bonding-capable imines 4,4'-dipyridylketone (dpk) and 4,4'-dipyridylamine (dpa)
      have been prepared and structurally characterized by single-crystal X-ray
      diffraction. {[Cu(pht)(dpk)].0.33CH(3)OH}(n) (1; pht = phthalate) possesses
      helical subunits built from the fusion of [Cu(dpk)](n) 3-fold double helices and
      [Cu(pht)](n) 3-fold helices with opposite handedness. The resulting achiral
      [Cu(pht)(dpk)](n) helices are conjoined by bridging phthalate carboxylate oxygen
      atoms to construct {Cu(2)O(2)} dimeric units, which serve as 8-connected nodes
      for a three-dimensional (3D) coordination polymer lattice with an unprecedented
      3(6)4(12)5(8)6(2) topology, evocative of a 3D Kagome lattice.
      {[Cu(2)(pht)(2)(dpa)].H(2)O}(n) (2) manifests homochiral septuple left-handed
      [Cu(2)O(2)(dpa)](n) helices formed by copper ions, phthalate oxygen atoms, and
      dpa ligands. The septuple helices are bracketed by pht anions to construct chiral
      one-dimensional nanobarrels with solvent-free "star-shaped" channels. Compounds 1
      and 2 display antiferromagnetic [J = -9.85(5) cm(-1)] and ferromagnetic [J =
      +1.36(3) cm(-1)] coupling across their {Cu(2)O(2)} dimeric units, respectively.

PMID- 19382761
TI  - Noncovalent interactions in a transition-metal triphenylphosphine complex: a
      density functional case study.
AB  - The binding enthalpy of a triphenylphosphine ligand in
      Ru(CO)Cl(PPh(3))(3)(CHCHPh) is studied with "standard" (BP86 and B3LYP),
      dispersion-corrected (B3LYP-D and B97-D), and highly parametrized (M05 and M06
      series) density functionals. An appropriate treatment of noncovalent interactions
      is mandatory because these turn out to account for a large fraction of the metal
      ligand interaction energy. Among the tested methods, B97-D and the M06 series of
      functionals best reproduce the experimental binding enthalpy value of Sponsler et
      al. (Inorg. Chem. 2007, 46, 561).

PMID- 19382762
TI  - 1D Coordination polymers constructed from anti-anti carboxylato-bridged
      Mn(III)(3)O(Brppz)(3) units: from long-range magnetic ordering to single-chain
      magnet behaviors.
AB  - The coordination of methanol and ethanol molecules was observed in the
      construction of three 1D coordination polymers composed of anti-anti carboxylato
      bridged Mn(III)(3)O(Brppz)(3) units [Brppz = 3-(5-bromine-2
      phenolate)pyrazolate]. The difference in these 1D complexes' structures induced
      by methanol and ethanol solvents leads to the variation of the magnetic
      properties. The methanol solvent product 1
      [Mn(III)(3)O(Brppz)(3)(MeOH)(3)(AcO)].0.5MeOH has a Mn(III)(3)O repeating unit
      with two octahedral configuration manganese(III) ions and one square-pyrimid
      configuration manganese(III) ion, showing a long-range magnetic ordering with a
      T(c) of 8.2 K, whereas the ethanol solvent products 2
      [Mn(III)(3)O(Brppz)(3)(C(2)H(5)OH)(4)(AcO)] (alpha-phase) and 3
      [Mn(III)(3)O(Brppz)(3)(C(2)H(5)OH)(4)(AcO)] (beta-phase) are polymorphs, both
      having a Mn(III)(3)O repeating unit with three octahedral configuration
      manganese(III) ions, displaying single-chain magnet behaviors. Products 2 and 3
      represent the first examples of polymorphs of single-chain magnets. Furthermore,
      the bridging carboxylate ligand in these 1D complexes was generated by the
      decomposition of beta-diketones via the retro-Claisen condensation reactions in
      the presence of strong bases.

PMID- 19382763
TI  - Palladium nanoparticle-catalyzed C-N bond formation. A highly regio- and
      stereoselective allylic amination by allyl acetates.
AB  - Palladium nanoparticles, generated in situ from the reaction of palladium(II)
      chloride, have been demonstrated to be an efficient catalyst for C-N bond
      formation. A variety of aliphatic and aromatic amines have been allylated by
      substituted and unsubstituted allyl acetates in high yields by using palladium
      nanoparticles in the presence of a base without any ligand. The allylations are
      highly regio- and stereoselective.

PMID- 19382764
TI  - Asymmetric total synthesis and revision of the absolute configuration of 4-keto
      clonostachydiol.
AB  - The first total synthesis of the 14-membered natural macrocyclic bislactone 4
      keto-clonostachydiol, along with its enantiomer, has been accomplished in 13
      steps with overall yields of 8.4% and 8.0%, respectively. The absolute
      configuration of 4-keto-clonostachydiol 1 has been revised as (5S,10S,13S).

PMID- 19382765
TI  - Synthesis of bis(m-phenylene)-32-crown-10-based discrete rhomboids driven by
      metal-coordination and complexation with paraquat.
AB  - Two bis(m-phenylene)-32-crown-10 derivatives containing two pyridyl or carboxyl
      groups were made. They were used to prepare three bis(m-phenylene)-32-crown-10
      based discrete rhomboids by coordination-driven self-assembly with high yields.
      The formation of these crown ether-based rhomboids was confirmed by NMR, UV-vis,
      CSI-TOF-MS, and elemental analysis. The complexation of these crown ether-based
      assemblies with paraquat (N,N'-dimethyl-4,4'-bipyridinium) was studied. The
      complexation of neutral bis(crown ether) rhomboid 1 with paraquat was found to be
      statistical with a 1:2 stoichiometry. The average apparent association constant
      K(av) of the complexation of rhomboid 1 with paraquat was found to be about
      8.8(+/-0.8) x 10(3) M(-1) in acetone, about 17 times higher than the reported
      association constant value for the complexation of the corresponding simple bis(m
      phenylene)-32-crown-10 with paraquat. This is possibly because the carboxylate
      groups provide additional noncovalent interactions between the host and guest. No
      obvious complexation was observed between the cationic rhomboids and paraquat
      when studied by NMR, UV-vis, and CSI-TOF-MS analysis. This could be attributed to
      the combination of the charge repulsion between cationic pyridinium rings and
      cationic platinum atoms and the weak pi-pi stacking and charge transfer
      interactions between the phenyl rings and the pyridinium rings caused by the
      electron-withdrawing effect of the cationic platinum atoms.

PMID- 19382766
TI  - Smart tissue culture: in situ monitoring of the activity of protease enzymes
      secreted from live cells using nanostructured photonic crystals.
AB  - Monitoring enzyme secretion in tissue culture has proved challenging because to
      date the activity cannot be continuously measured in situ. In this Letter, we
      present a solution using biopolymer loaded photonic crystals of anodized silicon.
      Shifts in the optical response by proteolytic degradation of the biopolymer
      provide label-free sensing with unprecedented low detection limits (1 pg) and
      calculation of kinetic parameters. The enhancement in sensitivity relative to
      previous photonic crystal sensors constitutes a change in the sensing paradigm
      because here the entire pore space is responsive to the secreted enzyme rather
      than just the pore walls. In situ monitoring is demonstrated by detecting
      secretion of matrix metalloprotease 9 from stimulated human macrophages.

PMID- 19382767
TI  - Knowledge-based approach to de novo design using reaction vectors.
AB  - A knowledge-based approach to the de novo design of synthetically feasible
      molecules is described. The method is based on reaction vectors which represent
      the structural changes that take place at the reaction center along with the
      environment in which the reaction occurs. The reaction vectors are derived
      automatically from a database of reactions which is not restricted by size or
      reaction complexity. A structure generation algorithm has been developed whereby
      reaction vectors can be applied to previously unseen starting materials in order
      to suggest novel syntheses. The approach has been implemented in KNIME and is
      validated by reproducing known synthetic routes. We then present applications of
      the method in different drug design scenarios including lead optimization and
      library enumeration. The method offers great potential for capturing and using
      the growing body of data on reactions that is becoming available through
      electronic laboratory notebooks.

PMID- 19382769
TI  - Control of two-photon absorption in organic compounds by pulse shaping: spectral
      dependence.
AB  - In this work, we investigate the control of the two-photon absorption process of
      a series of organic compounds via spectral phase modulation of the excitation
      pulse. We analyzed the effect of the pulse central wavelength on the control of
      the two-photon absorption process for each compound. Depending on the molecules'
      two-photon absorption position relative to the excitation pulse wavelength,
      different levels of coherent control were observed. By simulating the two-photon
      transition probability in molecular systems, taking into account the band
      structure and its positions, we could explain the experimental results trends. We
      observed that the intrapulse coherent interference plays an important role in the
      nonlinear process control besides just the pulse intensity modulation.

PMID- 19382768
TI  - Indium-catalyzed reductive alkylation of pyrroles with alkynes and hydrosilanes:
      selective synthesis of beta-alkylpyrroles.
AB  - Mixing readily available alkynes, pyrroles, and triethylsilane along with an
      indium catalyst was found to be an efficient procedure to introduce alkyl groups
      onto a beta-position of pyrroles in a complete regioselective manner. This is the
      first demonstration of catalytic beta-alkylation of pyrroles in a single step.

PMID- 19382770
TI  - Correlated exciton fluctuations in cylindrical molecular aggregates.
AB  - Femtosecond electronic relaxation dynamics of a cylindrical molecular aggregate
      are measured with transient grating (TG) and two-dimensional Fourier transform
      photon echo (PE) spectroscopies. The aggregates are double-walled cylindrical
      structures formed by self-assembly of amphiphilic cyanine dye molecules in water.
      The diameters of the inner and outer cylinders are approximately 6 and 10 nm. The
      linear absorption spectrum of the aggregate exhibits four spectrally resolved
      single exciton transitions corresponding to excited states localized on
      particular regions of the structure: (1) an excited state localized on the inner
      cylinder corresponds to the lowest energy transition at 16670 cm(-1); (2) a
      transition at 17150 cm(-1) represents a state localized on the outer cylinder,
      (3) whereas an overlapping peak found at 17330 cm(-1) is more closely associated
      with the inner cylinder; (4) an excited state delocalized between the inner and
      outer cylinder is assigned to a transition in the linear absorption spectrum at
      17860 cm(-1). TG spectra show a series of resonances reflecting the electronic
      structure of both the single and double exciton manifolds. In addition, PE
      spectra reveal coherent modulation of both diagonal and cross-peak amplitudes
      persisting for 100 fs, where the coherence frequency matches the energy gap
      between transitions 1 and 4 in the linear absorption spectrum. PE line shapes
      suggest correlated energy level fluctuations for the exciton states associated
      with these two transitions, which is consistent with this fairly long-lasting
      coherence at room temperature in aqueous solution. The impact of these
      correlations on Forster energy transfer efficiency is discussed. The observations
      imply fairly long-range correlations between the molecular sites (>0.6 nm), which
      in turn reflects the length scale of the environmental motion inducing the
      fluctuations. We suggest that this environmental motion is most likely associated
      with water confined inside the cylinder and/or fluctuations of the dye's
      aliphatic functional groups.

PMID- 19382772
TI  - Supported bilayers formed from different phospholipids on spherical silica
      substrates.
AB  - Spherical supported bilayer membranes (SS-BLMs) are very attractive candidates in
      modern bioanalytics and biorecognition studies. A uniform, facile method of
      preparing different SS-BLMs on silica beads is reported. Confocal fluorescence
      microscopy and cryo-TEM imaging have been used to characterize these SS-BLMs.
      Thermal analysis data and FRAP experiments show that the bilayer properties of
      the SS-BLM are consistent with those of lipid vesicles from which they are
      formed. The possibility of modulating the size, lipid type and functionality, and
      mechanical stability makes these rigid liposomes very attractive candidates in
      biosensors, drug screening, and gene delivery-related applications. This is
      especially true in work with native vesicle membranes derived from living cells
      because the existing methods can only accommodate anionic membranes to a limited
      extent.

PMID- 19382773
TI  - Methods for recovery of microorganisms and intact microbial polar lipids from oil
      water mixtures: laboratory experiments and natural well-head fluids.
AB  - Most of the world's remaining petroleum resource has been altered by in-reservoir
      biodegradation which adversely impacts oil quality and production, ultimately
      making heavy oil. Analysis of the microorganisms in produced reservoir fluid
      samples is a route to characterization of subsurface biomes and a better
      understanding of the resident and living microorganisms in petroleum reservoirs.
      The major challenges of sample contamination with surface biota, low abundances
      of microorganisms in subsurface samples, and viscous emulsions produced from
      biodegraded heavy oil reservoirs are addressed here in a new analytical method
      for intact polar lipids (IPL) as taxonomic indicators in petroleum reservoirs. We
      have evaluated the extent to which microbial cells are removed from the free
      water phase during reservoir fluid phase separation by analysis of model
      reservoir fluids spiked with microbial cells and have used the resultant
      methodologies to analyze natural well-head fluids from the Western Canada
      Sedimentary Basin (WCSB). Analysis of intact polar membrane lipids of
      microorganisms using liquid chromatography-mass spectrometry (LC-MS) techniques
      revealed that more than half of the total number of microorganisms can be
      recovered from oil-water mixtures. A newly developed oil/water separator allowed
      for filtering of large volumes of water quickly while in the field, which reduced
      the chances of contamination and alterations to the composition of the subsurface
      microbial community after sample collection. This method makes the analysis of
      IPLs (or indirectly microorganisms) from well-head fluids collected in remote
      field settings possible and reliable. To the best of our knowledge this is the
      first time that IPLs have been detected in well-head oil-water mixtures.

PMID- 19382774
TI  - On-line Fourier transform infrared spectrometric detection in gradient capillary
      liquid chromatography using nanoliter-flow cells.
AB  - A capillary liquid chromatographic system has been successfully interfaced with a
      mid-IR Fourier transform infrared (FT-IR) spectrometer. Spectra were recorded on
      line using a micromachined transmission CaF(2) cell (internal volume of 7.5 nL)
      that was placed on a dedicated beam condenser attached to the spectrometer.
      Linear gradients were run from (50:50) to (35:65) water (0.05% TFA)/acetonitrile
      in 15 min for the separation of standard solutions of four nitrophenols (4
      nitrophenol, 3-methyl-4-nitrophenol, 2,4-dinitrophenol, and 2-nitrophenol) in a
      reversed phase system, providing limits of detection between 35 and 94 ng on
      column. The changing background absorption due to gradient elution was
      successfully corrected by using a dedicated algorithm implemented in Matlab. When
      this chemometric data treatment was used, highly characteristic analyte spectra
      could be recorded as indicated by correlation coefficients between 89 and 95.8%,
      obtained when comparing mid-IR spectra of standard solutions and the spectra
      extracted from the chromatogram.

PMID- 19382775
TI  - Insights into metal-pi arene interactions of the highly Lewis acidic Rh2(4+) core
      with a broad set of pi-ligands: from ethylene to corannulene and C60-fullerene.
AB  - The first systematic theoretical investigation of interactions of the Lewis
      acidic Rh(II) centers with a number of pi-ligands having isolated unsaturated
      carboncarbon bonds (acetylene and ethylene) or delocalized pi-systems with planar
      (benzene, naphthalene, acenaphthylene, and pyrene) or curved surfaces
      (corannulene and the C(3)-hemifullerene), including the C(60)-fullerene, has been
      undertaken. The effect of size, geometry, site specificity, and curvature of pi
      ligands on their interaction energy with Rh(II) has been examined. The geometric
      and electronic structures of pi-adducts have been modeled at the DFT level of
      theory by using the hybrid Perdew-Burke-Ernzerhof parameter free exchange
      correlation functional (PBE0). The nature of Rh(II)-pi interactions was found to
      be similar in all products with the bonding energy ranging from 14.59 kcal/mol in
      the benzene adduct to 50.13 kcal/mol in the fullerene complex. Importantly, the
      quantitative evaluation of two bonding components, namely, ligand-to-metal and
      metal-to-ligand contributions, allowed us to rationalize the observed trends in
      pi-binding affinity of the selected ligands as well as in stability of the
      resulting products. These trends deduced from DFT calculations are important for
      considering the synthetic feasibility of novel pi-complexes in these systems.

PMID- 19382776
TI  - Sequential one-pot cyclizations: concise access to the ABCE tetracyclic framework
      of strychnos alkaloids.
AB  - A sequential one-pot biscyclization route to the ABCE tetracyclic framework of
      Strychnos alkaloids has been developed. Specifically, the AgOTf-mediated
      spirocyclization of an appropriately functionalized indole 3-carbinamide afforded
      a stable spiroindolenine intermediate; subsequent addition of DBU to the reaction
      mixture effected an unprecedented intramolecular aza-Baylis-Hillman reaction,
      delivering a tetracyclic product in 70% isolated yield.

PMID- 19382777
TI  - Self-assembly of hydroxy(phenyl)iodonium ions in acidic aqueous solution:
      preparation, and X-ray crystal structures of oligomeric phenyliodine(III)
      sulfates.
AB  - The treatment of [(diacetoxy)iodo]benzene with sodium bisulfate leads to the
      formation of oligomeric cationic species resulting from self-assembly of
      hydroxy(phenyl)iodonium ions, [PhIOH](+), in an aqueous acidic media. Depending
      on the PhI(OAc)(2):NaHSO(4) ratio, three new oligomeric products have been
      isolated and characterized by X-ray crystallography. The treatment of 5 equiv of
      PhI(OAc)(2) with 1 equiv of NaHSO(4).H(2)O affords the previously unknown mu-oxo
      [bis(acetoxy)iodo]benzene, PhI(OAc)OI(OAc)Ph, which was structurally
      characterized by X-ray crystallography. In the solid-state, this mu-oxo product
      forms an isolated diamond-core dimeric structure with pentagonal-planar iodine
      centers. The interaction of PhI(OAc)(2) with 1 equiv of NaHSO(4).H(2)O affords a
      solid-state polymeric phenyliodine(III) sulfate, [(PhIO)(3).SO(3)](n), in which
      bis(mu-oxo)triiodanyl dication repeat units are linked by sulfate anions. Three
      of these neighboring polymeric chains form pseudo triple-helix supramolecular
      structure, which translates along crystallographic b-axis. The reaction of
      PhI(OAc)(2) with 3 equiv of NaHSO(4).H(2)O results in the formation of a
      tetrameric phenyliodine(III) sulfate, PhI(OH)OSO(2)O(Ph)IOI(Ph)OSO(2)OI(OH)Ph,
      the solid state structure of which consists of mu-oxodiiodanyl dicationic species
      linked by sulfate anions to the terminal hydroxy(phenyl)iodonium groups. The
      pseudo double-helix structure of this compound formed by the strong
      intermolecular interactions between two neighbor mu-oxodiiodanyl dicationic
      fragments and four (per pseudo helix dimer) areas of sulfate anions to the
      terminal hydroxy(phenyl)iodonium groups interactions.

PMID- 19382778
TI  - Role of intermolecular interactions in oxygen transfer catalyzed by
      silsesquioxane trisilanolate vanadium(V).
AB  - The polyhedral oligomeric silsesquioxane trisilanolate vanadium(V) complex 1
      efficiently catalyzes oxidations at room temperature using cumyl hydroperoxide as
      the terminal oxidant. Sulfoxidations and N-oxidations have been carried out
      yielding the corresponding products in good yields. The addition of a Lewis base
      as a coligand can markedly affect reactivity, stability, and chemo- and stereo
      selectivity. A proposal for the intermolecular activation, using Gutmann analysis
      supported by MP2/TZVP calculations, is presented.

PMID- 19382779
TI  - Characterization of human skeletal muscle biopsy samples using shotgun
      proteomics.
AB  - We characterized the human muscle proteome by studying muscle biopsy specimens
      through four different workflows, using 1 or 2D peptide separation, SDS gels, or
      differential solubilization. By performing MS/MS analyses of 178 4-h LC
      separations derived from 31 patients, we identified more than 2000 proteins, and
      determined how 370 very abundant proteins behave upon differential
      solubilization. The resulting semiquantitative database should serve as a
      resource for muscle biochemistry.

PMID- 19382781
TI  - Submicrometer chemical patterning with high throughput using magnetolithography.
AB  - This letter demonstrates the ability to pattern surfaces chemically with
      submicrometer resolution by applying the simple and inexpensive
      magnetolithography (ML) method. This method allows fast patterning of large
      surfaces without having to face contamination problems or the need to remove the
      substrate from the solution. With ML it is possible to obtain pattern whose width
      is narrower than the width of the lines in the mask. By applying the green
      fluorescent protein (GFP), we were able to probe a 30 nm line of hydrophobic
      molecules patterned on a substrate coated with a hydrophilic monolayer.

PMID- 19382780
TI  - Indirect excitons in elevated traps.
AB  - We report on the study of indirect excitons in elevated traps. The transition
      from a normal to elevated trap results in the appearance of narrow lines in the
      emission spectrum. The density, temperature, and voltage dependences indicate
      that these lines correspond to the emission of individual states of indirect
      excitons in a disorder potential in the elevated trap.

PMID- 19382782
TI  - Alkylidenesilacyclopropanes derived from allenes: applications to the selective
      synthesis of triols and homoallylic alcohols.
AB  - Several alkylidenesilacyclopropanes were prepared by silver-mediated silylene
      transfer to allenes. Oxasilacyclopentanes derived from allenes were prepared with
      high regio- and diastereoselectivity by a two-step, one-flask
      silacyclopropanation/carbonyl insertion reaction. Triols and homoallylic alcohols
      were formed diastereoselectively by functionalizing the oxasilacyclopentanes. An
      optically active allene (>98% ee) was utilized to synthesize an enantiopure
      homoallylic alcohol in 96% ee.

PMID- 19382783
TI  - Adsorption isotherms of aqueous C12E6 and cetyltrimethylammonium bromide
      surfactants on solid surfaces in the presence of low molecular weight
      coadsorbents.
AB  - In this work, we evaluate the effects of the low molecular weight compounds
      toluene, phenol, and 1-hexanol on the adsorption of two surfactants on one solid
      surface. The surfactants are cetyltrimethylammonium bromide (CTAB, cationic) and
      hexaethylene glycol monododecyl ether (C12E6, nonionic). The surface is gold,
      although X-ray photoelectron spectroscopic analysis reveals the presence of a
      large number of oxygenated sites that render the surface hydrophilic (contact
      angle 10 degrees). Adsorption isotherms are measured using a quartz crystal
      microbalance with dissipation monitoring (QCM-D). Although our measurements do
      not allow the determination of the morphology of the aggregates directly, we
      rationalize our results by referring to AFM images from the literature. On the
      basis of primarily the dissipative signal and on AFM studies done by others, our
      results are consistent with CTAB forming a patchy cylindrical structure and C12E6
      likely yielding a monolayer structure. The presence of cosolutes almost doubles
      the mass of surface aggregates and increases the rigidness of the aggregates for
      CTAB, consistent with a morphological change from cylinders to flat bilayers.
      Part of the increase in adsorbed mass is likely due to increased surface area
      covered by admicelles. For C12E6, cosolutes cause small changes in the mass
      adsorption and essentially no change in the flexibility of surface aggregates.

PMID- 19382784
TI  - Nanomolar Hg(II) detection using Nile blue chemodosimeter in biological media.
AB  - A Nile blue-based chemodosimeter (1) was newly synthesized, and its application
      for detection of the Hg(2+) ion in 100% aqueous solution was demonstrated. Upon
      its addition into aqueous Hg(2+) ion solution, it exhibited a considerable blue
      shift in its absorption and emission spectra, driven by a desulfurization
      reaction. Detection at an emission of 652 nm was extremely sensitive (less than
      1.0 ppb), even in biological media such as blood plasma and albumin.

PMID- 19382785
TI  - Supramolecular organization of the main photosynthetic antenna complex LHCII: a
      monomolecular layer study.
AB  - The light-harvesting pigment-protein complex LHCII is a main antenna complex of
      the photosynthetic apparatus of plants, responsible for collecting light energy
      and also for photoprotection against overexcitation-induced damage. Realization
      of both functions depends on molecular organization of the complex. Monolayer
      technique has been applied to address the problem of supramolecular organization
      of LHCII. Analysis of the isotherms of compression of monomolecular films formed
      at the argon-water interface shows that LHCII appears in two phases: one
      characterized by the specific molecular area characteristic of trimeric and one
      of monomeric organization of LHCII. Monolayers of LHCII were deposited by means
      of the Langmuir-Blodgett technique to solid supports and examined by means of
      AFM, FTIR, fluorescence spectroscopy, and fluorescence lifetime imaging
      microscopy (FLIM). FTIR analysis shows that organization of the trimers of LHCII
      within a monolayer is associated with formation of intermolecular hydrogen bonds
      between neighboring polypeptides. The linear-dichroism FTIR analysis reveals that
      polypeptide fragments involved in intermolecular interactions are oriented at an
      angle of 67 degrees with respect to the normal axis to the plane of the layer.
      Fluorescence and fluorescence lifetime analysis reveal that the organization of
      LHCII within monolayers is associated with formation of the low-lying excitonic
      energy levels that can be potentially responsible for excess excitation
      quenching. FLIM and AFM reveal heterogeneous organization of LHCII monolayers, in
      particular, formation of ring-like structures. The potential of LHCII to form
      molecular structures characterized by pigment excitonic interactions is discussed
      in terms of regulation of the photosynthetic accessory function and
      photoprotection against overexcitation-induced damage.

PMID- 19382787
TI  - Stable and functionable mesoporous silica-coated gold nanorods as sensitive
      localized surface plasmon resonance (LSPR) nanosensors.
AB  - Core-shell structured Au NRs with a surface-exposed gold core and a mesoporous
      silica shell (MS Au NRs) were demonstrated as a promising platform for localized
      surface plasmon resonance (LSPR) based molecular sensing. Mesoporous silica shell
      not only allows the Au NRs core to be directly exposed to their surrounding
      environment but also stabilizes Au NRs dispersion in various water-organic
      mixtures and pure organic solvents. The LSPR band of MS Au NRS displays a stable
      and linear response in spectral shift to the changes in their surrounding
      refractive index with a sensitivity of 325 nm/RIU. To demonstrate the application
      of MS Au NRs as LSPR nanosensors in molecular sensing, the plasmon response to
      molecular adsorbates (GSH) was demonstrated. MS Au NRs provide a more stable and
      sensitive response than CTAB-capped Au NRs in GSH sensing. In addition, we have
      also demonstrated that the LSPR response of Au NRs is highly sensitive to changes
      of local refractive index in mesoporous silica shell, which renders the
      feasibility of using MS Au NRs as effective molecule-sensing platforms when
      mesoporous silica shells were functionalized with various chemical and biological
      ligands.

PMID- 19382786
TI  - Combined use of GC-TOF MS and UHPLC-(Q)TOF MS to investigate the presence of
      nontarget pollutants and their metabolites in a case of honeybee poisoning.
AB  - The combined use of gas chromatography (GC) and ultrahigh-pressure liquid
      chromatography (UHPLC), both coupled to time-of-flight mass spectrometry (TOF
      MS), has been explored in this work for the investigation of several cases of
      honeybee poisoning. The procedure applied involves a previous extraction with
      acetone followed by liquid-liquid extraction with dichloromethane. Both
      techniques, GC-TOF MS and UHPLC-(Q)TOF MS, have been applied to discover the
      presence of compounds that might be responsible of honeybee deaths. The
      application of a nontarget methodological approach to a first case of poisoning
      allowed the detection of the insecticide coumaphos at high concentration levels
      in the samples. The presence of possible metabolites of this organophosphorus
      insecticide was investigated by using both techniques. UHPLC-(Q)TOF MS showed its
      higher applicability in this case, as most of the metabolites were more polar
      than the parent compound. Four metabolites were identified by UHPLC-(Q)TOF MS,
      whereas only two of them were found by GC-TOF MS. The developed methodology was
      applied to other subsequent poisoning cases in which insecticides such as
      coumaphos, thiamethoxam, pyriproxyfen, and chlorfenvinphos were identified by
      both techniques, whereas GC-TOF MS also allowed the detection of fenitrothion and
      methiocarb. In all positive cases, the confirmation of the presence of the
      compound detected was feasible by means of accurate mass measurements of up to
      five ions together with their ion ratio evaluation.

PMID- 19382788
TI  - Metallization of the single component molecular semiconductor [Ni(ptdt)2] under
      very high pressure.
AB  - The four-probe electrical resistivity measurements on a single-component
      molecular semiconductor [Ni(ptdt)(2)] (Ni(S(8)C(9)H(6))(2)) was performed up to
      20.7 GPa by using a diamond anvil cell. A newly improved method was employed to
      reduce the effect of uniaxial pressure. The semiconducting behavior persisted up
      to 17.9 GPa. The pressure-induced metallization began to appear at 18.9 GPa, and
      the complete metallic behavior down to 1 K was observed at 19.9 GPa.

PMID- 19382789
TI  - Chemical redox reactions induced by cryptoelectrons on a PMMA surface.
AB  - We show that pristine PMMA can spontaneously transfer electrons to species in a
      liquid, thereby inducing a variety of electron transfer reactions. The electrons
      that are transferred we call cryptoelectrons; these have a surface density of the
      order of 5 x 10(13) cm(-2) and are at a considerably more negative reduction
      potential than the PMMA bonding electrons. For example, metal ions including
      Ag(+), Cu(2+), and Pd(2+) were reduced and plated on a PMMA surface and
      Fe(CN)(6)(3-) was reduced to Fe(CN)(6)(4-). Moreover, protons were reduced when
      PMMA powder was dropped into a slightly acidic solution, resulting in a pH
      increase and hydrogen generation. Chemiluminescence was produced in a solution
      containing Ru(bpy)(3)(2+) and S(2)O(8)(2-) with the addition of PMMA powder.
      These results clearly demonstrate that there are available electrons in PMMA that
      can participate in redox reactions at a rather negative potential. We also show
      that contacting PMMA with Teflon depletes this electronic surface charge.
      However, the PMMA used for a redox reaction or contacted with Teflon that was
      depleted of the electronic surface charge could be recharged by contacting with a
      suitable reductant.

PMID- 19382790
TI  - Classical versus bridged allyl ligands in magnesium complexes: the role of
      solvent.
AB  - Magnesium allyl complexes are regularly isolated with classical, sigma-bonded
      ligands, and this has been thought to be their preferred mode of bonding. Density
      functional theory calculations confirm that such bonding is the most stable mode
      when coordinated bases are present, but in their absence, pi-bonded forms are
      expected to be lower in energy. The isolation of the unsolvated
      [Mg{C(3)(SiMe(3))(2)H(3)}(2)](2) complex supports this prediction, as it is a
      dinuclear species in which two allyl ligands bridge the metals and display cation
      pi interactions with them.

PMID- 19382791
TI  - Comparative molecular simulation study of CO2/N2 and CH4/N2 separation in
      zeolites and metal-organic frameworks.
AB  - In this work, a systematic molecular simulation study was performed to compare
      the separation of CO2/N2 and CH4/N2 mixtures in two different classes of
      nanoporous materials, zeolites, and metal-organic frameworks (MOFs). For this
      purpose, three zeolites (MFI, LTA, and DDR) and seven MOFs (Cu-BTC, MIL-47 (V),
      IRMOF-1, IRMOF-12, IRMOF-14, IRMOF-11, and IRMOF-13) were chosen as the
      representatives to compare. On the basis of the validated force fields, both
      adsorption selectivity and pure CO2 and CH4 adsorption isotherms were simulated.
      The results show that although MOFs perform much better for gas storage, their
      separation performance is comparable to zeolites; for the systems with the
      preferable component having a larger quadrupolar moment, both zeolites and MOFs
      can enhance the separation selectivity, and in contrast they both reduce the
      selectivity. In addition, we show that ideal adsorbed solution theory (IAST)
      gives a very reasonable prediction of the mixture adsorption isotherms both in
      zeolites and in MOFs if the pure component isotherms are known. We demonstrate
      that the difference in quadrupolar moment of the components is an important
      property that has to be considered in the selection of a membrane material.

PMID- 19382792
TI  - FvVE1 regulates biosynthesis of the mycotoxins fumonisins and fusarins in
      Fusarium verticillioides.
AB  - The veA gene positively regulates sterigmatocystin production in Aspergillus
      nidulans and aflatoxin production in Aspergillus parasiticus and Aspergillus
      flavus . Whether veA homologues have a role in regulating secondary metabolism in
      other fungal genera is unknown. In this study, we examined the role of the veA
      homologue, FvVE1, on the production of two mycotoxin families, fumonisins and
      fusarins, in the important corn pathogen Fusarium verticillioides . We found that
      FvVE1 deletion completely suppressed fumonisin production on two natural
      substrates, corn and rice. Furthermore, our results revealed that FvVE1 is
      necessary for the expression of the pathway-specific regulatory gene FUM21 and
      structural genes in the fumonisin biosynthetic gene (FUM) cluster. FvVE1 deletion
      also blocked production of fusarins. The effects of FvVE1 deletion on the
      production of these toxins were found to be the same in two separate mating
      types. Our results strongly suggest that FvVE1 plays an important role in
      regulating mycotoxin production in F. verticillioides .

PMID- 19382793
TI  - Tautomerism in cytosine and uracil: an experimental and theoretical core level
      spectroscopic study.
AB  - The O, N, and C 1s core level photoemission spectra of the nucleobases cytosine
      and uracil have been measured in the vapor phase, and the results have been
      interpreted via theoretical calculations. Our calculations accurately predict the
      relative binding energies of the core level features observed in the experimental
      photoemission results and provide a full assignment. In agreement with previous
      work, a single tautomer of uracil is populated at 405 K, giving rise to
      relatively simple spectra. At 450 K, three tautomers of cytosine, one of which
      may consist of two rotamers, are identified, and their populations are
      determined. This resolves inconsistencies between recent laser studies of this
      molecule in which the rare imino-oxo tautomer was not observed and older
      microwave spectra in which it was reported.

PMID- 19382794
TI  - V-shaped 4,6-bis(arylvinyl)pyrimidine oligomers: synthesis and optical
      properties.
AB  - A series of V-shaped 4,6-bis(arylvinyl)pyrimidines have been efficiently prepared
      by aldol condensation between 4,6-dimethylpyrimidine and the appropriate aromatic
      aldehyde. The methodology also proved successful when dendritic first generation
      poly(phenylenevinylene) aldehydes were used. Moreover, asymmetrically
      functionalized molecules were also obtained by the stepwise incorporation of arms
      in a controlled manner. The optical absorption and emission properties of these
      systems were studied in different solvents and media. The materials display
      strong emission solvatochromism that is reflected by a large red shift in their
      fluorescence emission maxima on increasing the solvent polarity. This change is
      accompanied by a successive decrease in fluorescence intensity. This behavior
      suggests a highly polar emitting state, which is characteristic of compounds that
      undergo an internal charge transfer upon excitation. The abilities of these
      molecules to function as colorimetric and luminescence pH sensors were
      demonstrated with dramatic color changes and luminescence switching upon the
      introduction of acid.

PMID- 19382795
TI  - High-sensitivity amperometric biosensors based on ferrocene-modified linear
      poly(ethylenimine).
AB  - Amperometric biosensors for glucose and hydrogen peroxide have been built by
      immobilizing glucose oxidase (GOX) and horseradish peroxidase (HRP) in cross
      linked films of ferrocene-modified linear poly(ethylenimine). At pH 7, the
      glucose sensors generated limiting catalytic current densities of 1.2 mA/cm2.
      These current densities are approximately 4 times higher than those with other
      ferrocene-based redox polymers and are comparable to the highest reported values
      for osmium-based redox polymers with GOX. Because of the high sensitivity of
      these films (73 nA/cm2.microM), glucose concentrations in the micromolar range
      could be detected. Similarly, sensors were constructed with HRP-generated current
      densities of 0.9 mA/cm2 under saturation conditions and sensitivities of 500
      nA/cm2.microM. The results show that the ability of Fc-LPEI to effectively
      communicate with a variety of enzymes has potential applications in measuring low
      substrate concentrations in implantable biosensors and producing high current
      outputs in enzymatic biofuel cells.

PMID- 19382796
TI  - Taking advantage of nonspecific trypsin cleavages for the identification of seed
      storage proteins in cereals.
AB  - The lack of basic amino acids in seed storage proteins has resulted in the
      proposal to use chymotrypsin in their study. A comparative study of trypsin and
      chymotrypsin digestion initially confirmed this preference; however, reanalysis
      of the trypsin data set defining the specificity as 'semitrypsin' provided enough
      extra data to bridge the gap between both proteases. Rationale as to why numerous
      semitryptic peptides are observed in the study of these proteins is provided.

PMID- 19382797
TI  - Gas-phase kinetics of chlorosilylene reactions. I. ClSiH + Me3SiH: absolute rate
      measurements and theoretical calculations for prototype Si-H insertion reactions.
AB  - Time-resolved studies of chlorosilylene, ClSiH, generated by the 193 nm laser
      flash photolysis of 1-chloro-1-silacyclopent-3-ene, have been carried out to
      obtain rate constants for its bimolecular reaction with trimethylsilane,
      Me(3)SiH, in the gas phase. The reaction was studied at total pressures up to 100
      torr (with and without added SF(6)) over the temperature range 297-407 K. The
      rate constants were found to be pressure independent and gave the following
      Arrhenius equation: log(k/cm(3) molecule(-1) s(-1)) = (-13.97 +/- 0.25) + (12.57
      +/- 1.64) kJ mol(-1)/RT ln 10. The Arrhenius parameters are consistent with a
      mechanism involving an intermediate complex, whose rearrangement is the rate
      determining step. Quantum chemical calculations of the potential energy surface
      for this reaction and also the reactions of ClSiH with SiH(4) and the other
      methylsilanes support this conclusion. Comparisons of both experiment and theory
      with the analogous Si-H insertion processes of SiH(2) and SiMe(2) show that the
      main factor causing the lower reactivity of ClSiH is the secondary energy
      barrier. The calculations also show the existence of a novel intramolecular H
      atom exchange process in the complex of ClSiH with MeSiH(3).

PMID- 19382799
TI  - Synthesis and photophysical properties of donor- and acceptor-substituted 1,7
      bis(arylalkynyl)perylene-3,4:9,10-bis(dicarboximide)s.
AB  - A series of 1,7-bis(arylethynyl)-N,N'-bis[2,6-diisopropylphenyl]perylene-3,4:9,10
      bis(dicarboximide)s has been obtained from Sonogashira coupling of the 1,7
      dibromoperylene-3,4:9,10-bis(dicarboximide) with p-substituted phenylacetylenes
      in which the p-substituents include pi-donors (dialkylamino, diarylamino, p
      (diarylamino)phenyl, alkoxy) and pi-acceptors (diarylboryl, p
      (diarylboryl)phenyl). The bis(arylethynyl)-substituted chromophores all show two
      reversible molecular reductions and are all slightly more readily reduced than
      unsubstituted perylene-3,4:9,10-bis(dicarboximide)s with the electrochemical
      potentials being rather insensitive to the pi-donor or acceptor nature of the
      aryl group. The amine derivatives also show reversible molecular oxidations. The
      UV-vis spectra of the chromophores with alkoxy and boryl substituents show red
      shifted absorptions relative to unsubstituted perylene diimides with discernible
      vibronic structure. In contrast, the lowest energy absorptions of the amino
      derivatives are broad and structureless, suggesting donor-to-acceptor charge
      transfer character. Transient absorption spectra for the amine derivatives were
      interpreted in terms of ultrafast charge separation, followed by charge
      recombination on a time scale of ca. 80-2000 ps. Two compounds were also
      synthesized in which an additional stronger, but more weakly coupled, donor group
      is linked by a nonconjugated bridge to the p-amine donor, to investigate the
      effect on the charge recombination lifetimes; however, the lifetimes of the
      charge-separated states, ca. 150 and 1000 ps, were within the range observed for
      the simple amine systems. Finally, the two-photon absorption properties of three
      bis(arylethynyl)-substituted derivatives were investigated, along with those of
      1,7-di(pyrrolidin-1-yl)-N,N'-bis[2,6-diisopropylphenyl]perylene-3,4:9,10
      bis(dicarboximide). As with other perylene-3,4:9,10-bis(dicarboximide)s and
      related species, strong two-photon absorption (>1000 GM) was observed for three
      of these species close to the one-photon absorption edge; however, an additional
      feature (100-500 GM) was also observed at longer wavelength. An example with (p
      aminophenyl)ethylnyl substituents showed a qualitatively different two-photon
      spectrum with a cross-section >500 GM being observed over a broad wavelength
      range.

PMID- 19382798
TI  - Role of nucleobase energetics and nucleobase interactions in single-stranded
      peptide nucleic acid charge transfer.
AB  - Self-assembled monolayers of single-stranded (ss) peptide nucleic acids (PNAs)
      containing seven nucleotides (TTTXTTT), a C-terminus cysteine, and an N-terminus
      ferrocene redox group were formed on gold electrodes. The PNA monomer group (X)
      was selected to be either cytosine (C), thymine (T), adenine (A), guanine (G), or
      a methyl group (Bk). The charge transfer rate through the oligonucleotides was
      found to correlate with the oxidation potential of X. Kinetic measurements and
      computational studies of the ss-PNA fragments show that a nucleobase mediated
      charge transport mechanism in the deep tunneling superexchange regime can explain
      the observed dependence of the kinetics of charge transfer on the PNA sequence.
      Theoretical analysis suggests that the charge transport is dominantly hole
      mediated and takes place through the filled bridge orbitals. The strongest
      contribution to conductance comes from the highest filled orbitals (HOMO, HOMO-1,
      and HOMO-2) of individual bases, with a rapid drop off in contributions from
      lower lying filled orbitals. Our studies further suggest that the linear
      correlation observed between the experimental charge transfer rates and the
      oxidation potential of base X arises from weak average interbase couplings and
      similar stacking geometries for the four TTTXTTT systems.

PMID- 19382800
TI  - Improvement of the platinum nanoparticles-carbon substrate interaction by
      insertion of a thiophenol molecular bridge.
AB  - The effect of thiophenol layer grafted on carbon for platinum catalyst
      stabilization was studied. The grafted layer was prepared by reduction of 4
      thiophenoldiazonium ions in the presence of Vulcan XC72 substrate. The grafted
      layer was characterized by elemental analysis, thermogravimetric analysis coupled
      with mass spectrometry, and X-ray photoelectron spectroscopy. Platinum
      nanoparticles prepared by the "water in oil" microemulsion method were then
      deposited on modified substrates and bare Vulcan XC72. The platinum stability
      improvement was characterized by in situ X-ray diffraction and electrochemical
      aging. These experiments enabled to evidence a lower crystallite growth during
      heat treatment under hydrogen atmosphere and a lower active surface area loss for
      platinum particles deposited on modified substrates compared to those deposited
      on bare Vulcan XC72. This stability improvement can be attributed to a better
      interaction between platinum particles and carbon substrate due to the thiophenol
      molecular bridge.

PMID- 19382801
TI  - Do concentration cells store charge in water? Comment on can water store charge?

PMID- 19382802
TI  - Solvent effect on 1,2-O-(1-ethylpropylidene)-alpha-D-glucofuranose organogel
      properties.
AB  - The solvent effect on organogel formation in nitrobenzene and chlorobenzene using
      1,2-O-(1-ethylpropylidene)-alpha-d-glucofuranose (1) as the gelator is presented.
      Fourier transform infrared (FTIR) spectroscopy revealed that hydrogen bonding
      between the molecules of gelator 1 is the main driving force for gelator self
      aggregation. The gels are characterized by different hydrogen-bonding patterns,
      which are reflected in a different microstructure of the networks. The morphology
      of fibers of nitrobenzene organogel consists of straight, rod-like, and thinner
      fibers, in comparison to the elongated but generally not straight and thicker
      fibers in chlorobenzene organogel. The thermal stability of gels also differs,
      and the DeltaH is equal to 50.1 and 65.0 kJ/mol for nitrobenzene and
      chlorobenzene gels, respectively. The properties of the gels reported here were
      compared to benzene and toluene gels of 1 presented in previous work and
      correlated with different solvent parameters: epsilon, delta, and E(T)(30). We
      have shown that the polarity of the solvent influences the thermal stability of
      the gel, the hydrogen-bonding network, and finally the structure of gel network.
      Therefore, in the studied sugar-based gelator, the hydrogen bonding alone is
      insufficient to fully describe the gelation process.

PMID- 19382803
TI  - Dendrimers bind human serum albumin.
AB  - Dendrimers are synthetic, highly branched, spherical macromolecules with
      nanometer dimensions and potential applications in DNA and drug delivery systems.
      Human serum albumin (HSA) is a major transporter for delivering several
      endogenous compounds and drugs in vivo. The aim of this study was to examine the
      interaction of human serum albumin with several dendrimers such as mPEG-PAMAM
      (G3), mPEG-PAMAM (G4), and PAMAM (G4) at physiological conditions, using constant
      protein concentration and various dendrimer compositions. FTIR, UV-visible, CD,
      and fluorescence spectroscopic methods were used to analyze macromolecule binding
      mode, the binding constant and the effects of dendrimers complexation on HSA
      stability and conformation. Structural analysis showed that dendrimers bind HSA
      via polypeptide polar groups (hydrophilic) with number of bound polymer (n) 1.08
      (mPEG-PAMAM-G3), 1.50 (mPEG-PAMAM-G4), and 0.96 (PAMAM-G4). The overall binding
      constants estimated were of KmPEG-G3=1.3 (+/-0.2)x10(4) M(-1), KmPEG-G4=2.2 (+/
      0.4)x10(4) M(-1), and KPAMAM-G4=2.6 (+/-0.5)x10(4) M(-1). HSA conformation was
      altered by dendrimers with a major reduction of alpha-helix and increase in
      random coil and turn structures suggesting a partial protein unfolding.

PMID- 19382804
TI  - Toward asymmetric aldol-Tishchenko reactions with enolizable aldehydes: access to
      defined configured stereotriads, tetrads, and stereopentads.
AB  - Asymmetric aldol-Tishchenko reactions of enolizable aldehydes and ketones in the
      presence of chiral BINOLTi(OtBu)(2)/cinchona alkaloids complexes are described.
      Different configurative outcomes of these reactions depend on an equilibration
      through a retro aldol/aldol sequence and can be influenced by the configurative
      architecture of substrates. The results are explained by means of transition
      state models and rate constants. These considerations offer a fine-tuning of
      diastereoselectivity in aldol-Tishchenko reactions. Extensions of this research
      give access to defined configured stereotriads, stereotetrads, and stereopentads.

PMID- 19382806
TI  - Mitsunobu and related reactions: advances and applications.

PMID- 19382805
TI  - A22 disrupts the bacterial actin cytoskeleton by directly binding and inducing a
      low-affinity state in MreB.
AB  - S-(3,4-Dichlorobenzyl)isothiourea (A22) disrupts the actin cytoskeleton of
      bacteria, causing defects of morphology and chromosome segregation. Previous
      studies have suggested that the actin homologue MreB itself is the target of A22,
      but there has been no direct observation of A22 binding to MreB and no
      mechanistic explanation of its mode of action. We show that A22 binds MreB with
      at least micromolar affinity in its nucleotide-binding pocket in a manner that is
      sterically incompatible with simultaneous ATP binding. A22 negatively affects
      both the time course and extent of MreB polymerization in vitro in the presence
      of ATP. A22 prevents assembly of MreB into long, rigid polymers, as determined by
      both fluorescence microscopy and sedimentation assays. A22 increases the critical
      concentration of ATP-bound MreB assembly from 500 nM to approximately 2000 nM. We
      therefore conclude that A22 is a competitive inhibitor of ATP binding to MreB.
      A22-bound MreB is capable of polymerization, but with assembly properties that
      more closely resemble those of the ADP-bound state. Because the cellular
      concentration of MreB is in the low micromolar range, this mechanism explains the
      ability of A22 to largely disassemble the actin cytoskeleton in bacterial cells.
      It also represents a novel mode of action for a cytoskeletal drug and the first
      biochemical characterization of the interaction between a small molecule
      inhibitor of the bacterial cytoskeleton and its target.

PMID- 19382807
TI  - Hydroelectric voltage generation based on water-filled single-walled carbon
      nanotubes.
AB  - A DFT/MD mutual iterative method was employed to give insights into the mechanism
      of voltage generation based on water-filled single-walled carbon nanotubes
      (SWCNTs). Our calculations showed that a constant voltage difference of several
      mV would generate between the two ends of a carbon nanotube, due to interactions
      between the water dipole chains and charge carriers in the tube. Our work
      validates this structure of a water-filled SWCNT as a promising candidate for a
      synthetic nanoscale power cell, as well as a practical nanopower harvesting
      device at the atomic level.

PMID- 19382810
TI  - Integrated microfluidic system with chemiluminescence detection for single cell
      analysis after intracellular labeling.
AB  - This work describes the first application of microchip electrophoresis with
      chemiluminescence detection (MCE-CL) in single cell analysis. Human red blood
      cells were assayed to determine intracellular content of glutathione (GSH).
      Intracellular GSH was first labeled by incubating cells with diazo-luminol, and
      then individual cells were injected, in-line lysed, and MCE separated. CL
      detection was based on the oxidation reaction of luminol-labeled GSH with NaBrO.
      The MCE-CL assay had a linear calibration curve over a range from 0.2-90 amol GSH
      injected with a correlation coefficient of 0.9991 and a detection limit of 50
      zmol or 3.6 x 10(-9) M (S/N = 3). The average content of GSH in individual human
      red blood cells was found 64.9 amol (n = 17). Compared with the MCE methods with
      laser induced fluorescence detection (LIF) reported so far for single cell
      analysis, the present MCE-CL assay of GSH is simple and about 100 times more
      sensitive.

PMID- 19382811
TI  - Two dimensional mass mapping as a general method of data representation in
      comprehensive analysis of complex molecular mixtures.
AB  - A recent proteomics-grade (95%+ sequence reliability) high-throughput de novo
      sequencing method utilizes the benefits of high resolution, high mass accuracy,
      and the use of two complementary fragmentation techniques collision-activated
      dissociation (CAD) and electron capture dissociation (ECD). With this high
      fidelity sequencing approach, hundreds of peptides can be sequenced de novo in a
      single LC-MS/MS experiment. The high productivity of the new analysis technique
      has revealed a new bottleneck which occurs in data representation. Here we
      suggest a new method of data analysis and visualization that presents a
      comprehensive picture of the peptide content including relative abundances and
      grouping into families. The 2D mass mapping consists of putting the molecular
      masses onto a two-dimensional bubble plot, with the relative monoisotopic mass
      defect and isotopic shift being the axes and with the bubble area proportional to
      the peptide abundance. Peptides belonging to the same family form a compact group
      on such a plot, so that the family identity can in many cases be determined from
      the molecular mass alone. The performance of the method is demonstrated on the
      high-throughput analysis of skin secretion from three frogs, Rana ridibunda, Rana
      arvalis, and Rana temporaria. Two dimensional mass maps simplify the task of
      global comparison between the species and make obvious the similarities and
      differences in the peptide contents that are obscure in traditional data
      presentation methods. Even biological activity of the peptide can sometimes be
      inferred from its position on the plot. Two dimensional mass mapping is a general
      method applicable to any complex mixture, peptide and nonpeptide alike.

PMID- 19382808
TI  - Applications of 1-alkenyl-1,1-heterobimetallics in the stereoselective synthesis
      of cyclopropylboronate esters, trisubstituted cyclopropanols and 2,3
      disubstituted cyclobutanones.
AB  - 1-Alkenyl-1,1-heterobimetallics are potentially very useful in stereoselective
      organic synthesis but are relatively unexplored. Introduced herein is a practical
      application of 1-alkenyl-1,1-heterobimetallic intermediates in the synthesis of
      versatile cyclopropyl alcohol boronate esters, which are valuable building
      blocks. Thus, hydroboration of 1-alkynyl-1-boronate esters with
      dicyclohexylborane generates 1-alkenyl-1,1-diboro species. In situ
      transmetalation with dialkylzinc reagents furnishes 1-alkenyl-1,1-borozinc
      heterobimetallic intermediates. Addition of the more reactive ZnC bond to
      aldehydes generates the key B(pin) substituted allylic alkoxide intermediates. An
      in situ alkoxide directed cyclopropanation proceeds with the formation of two
      more CC bonds, affording cyclopropyl alcohol boronate esters with three new
      stereocenters in 58-89% isolated yields and excellent diastereoselectivities
      (>15:1 dr). Oxidation of the BC bond provides trisubstituted alpha
      hydroxycyclopropyl carbinols as single diastereomers in good to excellent yields
      (75-93%). Facile pinacol-type rearrangement of the alpha-hydroxycyclopropyl
      carbinols provides access to both cis- and trans-2,3-disubstituted cyclobutanones
      with high stereoselectivity (>17:1 dr in most cases) from a common starting
      material. This methodology has been applied in the synthesis of quercus lactones
      A and B.

PMID- 19382812
TI  - Three-dimensional metal azide coordination polymers with amino carboxylate
      coligands: synthesis, structure, and magnetic properties.
AB  - The reaction of M(II) ions with azido ligands in the presence of different amino
      carboxylic acids gave four three-dimensional metal-azido coordination polymers,
      [Mn(3,5-daba)(N(3))](n) (1), [Cd(3,5-daba)(N(3))](n) (2; 3,5-daba = 3,5
      diaminobenzoate), [Mn(4-aba)(N(3))](n) (3; 4-aba = 4-aminobenzoate), and
      [Cu(2)(gly)(2)(N(3))(2)](n) (4; gly = glycinate), which display different
      topological structures. Polymers 1 and 2 present 4,6-connected 3D networks with
      different Schlafli symbols. However, 3 and 4 feature an unprecedented trinodal
      3,6-connected network with the Schlafli symbol (4(2).6)(4.6(2))(4(3).6(6).8(6))
      and an unusual 4-connected 3D net with the Lonsdaleite (hexagonal diamond)
      topology, respectively. Magnetic susceptibility measurements revealed dominant
      antiferromagnetic couplings for 1 and 3 and an overall dominant ferromagnetic
      coupling for 4, which presents metamagnetic behavior with a magnetic phase
      transition at a critical temperature of 6 K and a transition field of ca. 6030
      Oe. The results demonstrate that the EE azido and syn-anti carboxylato bridges in
      our cases induce an antiferomagnetic interaction, and the anti-anti carboxylato
      bridge in 4 mediates a ferromagnetic interaction. The magnetic interaction
      through the EO azido bridge in 3 and 4 has a dependence on the value of the M-N-M
      bond angle.

PMID- 19382813
TI  - CO oxidation over AuPd(100) from ultrahigh vacuum to near-atmospheric pressures:
      the critical role of contiguous Pd atoms.
AB  - It is demonstrated that gas-phase CO pressure higher than approximately 0.1 Torr
      is required to segregate a sufficient amount of Pd to the surface of a well
      annealed AuPd(100) sample to form contiguous Pd sites. These contiguous sites are
      critical in dissociating O(2) for low-temperature CO oxidation, where CO
      chemisorbed on Au sites clearly participates in the reaction at temperatures
      below approximately 400 K. Measured reaction kinetics demonstrates that the
      higher reaction rate is achieved on a surface with higher coverages of contiguous
      Pd sites.

PMID- 19382814
TI  - Hydrophobic dimerization and thermal dissociation of perylenediimide-linked DNA
      hairpins.
AB  - The structure and properties of hairpin-forming bis(oligonucleotide) conjugates
      possessing perylenediimide (PDI) chromophores as hairpin linkers have been
      investigated using a combination of spectroscopic and computational methods.
      These conjugates exist predominantly as monomer hairpins at room temperature in
      the absence of added salt and as head-to-head hairpin dimers in the presence of
      >50 mM NaCl. The hairpin dimer structure is consistent with the results of small
      angle X-ray scattering in aqueous solution and molecular dynamics simulation. The
      structure of the nonconjugated PDI dimer in water is investigated using potential
      of mean force calculations. The salt dependence is attributed to increased cation
      condensation in the hairpin dimer vs monomer. Upon heating at low salt
      concentrations, the hairpin dimer undergoes sequential dissociation to form the
      monomer hairpin followed by conversion to a random coil structure; whereas at
      high salt concentrations both dissociation processes occur over the same
      temperature range. The monomer and dimer hairpins have distinct spectroscopic
      properties both in the ground state and excited singlet state. The UV and CD
      spectra provide evidence for electronic interaction between PDI and the adjacent
      base pair. Low fluorescence quantum yields are observed for both the monomer and
      dimer. The transient absorption spectrum of the dimer undergoes time-dependent
      spectral changes attributed to a change in the PDI-PDI torsional angle from ca.
      20 degrees in the Franck-Condon singlet state to ca. 0 degrees in the relaxed
      singlet state, a process which occurs within ca. 40 ps.

PMID- 19382815
TI  - An N-aroyltransferase of the BAHD superfamily has broad aroyl CoA specificity in
      vitro with analogues of N-dearoylpaclitaxel.
AB  - The native N-debenzoyl-2'-deoxypaclitaxel:N-benzoyltransferase (NDTBT), from
      Taxus plants, transfers a benzoyl group from the corresponding CoA thioester to
      the amino group of the beta-phenylalanine side chain of N-debenzoyl-2'
      deoxypaclitaxel, which is purportedly on the paclitaxel (Taxol) biosynthetic
      pathway. To elucidate the substrate specificity of NDTBT overexpressed in
      Escherichia coli, the purified enzyme was incubated with semisynthetically
      derived N-debenzoyltaxoid substrates and aroyl CoA donors (benzoyl; ortho-, meta
      , and para-substituted benzoyls; various heterole carbonyls; alkanoyls; and
      butenoyl), which were obtained from commercial sources or synthesized via a mixed
      anhydride method. Several unnatural N-aroyl-N-debenzoyl-2'-deoxypaclitaxel
      analogues were biocatalytically assembled with catalytic efficiencies
      (V(max)/K(M)) ranging between 0.15 and 1.74 nmol.min(-1).mM(-1). In addition,
      several N-acyl-N-debenzoylpaclitaxel variants were biosynthesized when N
      debenzoylpaclitaxel and N-de(tert-butoxycarbonyl)docetaxel (i.e., 10-deacetyl-N
      debenzoylpaclitaxel) were used as substrates. The relative velocity (v(rel)) for
      NDTBT with the latter two N-debenzoyl taxane substrates ranged between
      approximately 1% and 200% for the array of aroyl CoAs compared to benzoyl CoA.
      Interestingly, NDTBT transferred hexanoyl, acetyl, and butyryl more rapidly than
      butenoyl or benzoyl from the CoA donor to taxanes with isoserinoyl side chains,
      whereas N-debenzoyl-2'-deoxypaclitaxel was more rapidly converted to its N
      benzoyl derivative than to its N-alkanoyl or N-butenoyl congeners. Biocatalytic N
      acyl transfer of novel acyl groups to the amino functional group of N
      debenzoylpaclitaxel and its 2'-deoxy precursor reveal the surprisingly
      indiscriminate specificity of this transferase. This feature of NDTBT potentially
      provides a tool for alternative biocatalytic N-aroylation/alkanoylation to
      construct next generation taxanes or other novel bioactive diterpene compounds.

PMID- 19382817
TI  - Conversion of the common food constituent 5-hydroxymethylfurfural into a
      mutagenic and carcinogenic sulfuric acid ester in the mouse in vivo.
AB  - 5-Hydroxymethylfurfural (HMF), formed by acid-catalyzed dehydration and in the
      Maillard reaction from reducing sugars, is found at high levels in numerous
      foods. It was shown to initiate colon aberrant crypt foci in rats and skin
      papillomas and hepatocellular adenomas in mice. HMF is inactive in in vitro
      genotoxicity tests using standard activating systems but is activated to a
      mutagen by sulfotransferases. The product, 5-sulfoxymethylfurfural (SMF), is a
      stronger carcinogen than HMF. SMF has not been detected in the biotransfomation
      experiments conducted on HMF in humans and animals in vivo up to date. Here, we
      report pharmacokinetic properties of HMF and SMF in FVB/N mice. Sensitive assays
      for the quantification of HMF and SMF by LC-MS/MS multiple reaction monitoring
      were devised. SMF, intravenously injected (4.4 micromol/kg body mass), showed
      first-order elimination kinetics in blood plasma (t(1/2) = 7.9 min). HMF,
      injected intravenously (793 micromol/kg body mass), demonstrated biphasic
      kinetics in plasma (t(1/2) = 1.7 and 28 min for the initial and terminal
      elimination phases, respectively); the volume of distribution of the central
      compartment corresponded approximately to the total body water. The maximum SMF
      plasma level was observed at the first sampling time, 2.5 min after HMF
      administration. On the basis of these kinetic data, it was estimated that between
      452 and 551 ppm of the initial HMF dose was converted to SMF and reached the
      circulation. It is likely that additional SMF reacted with cellular structures at
      the site of generation and thus is ignored in this balance. Our work supports the
      hypothesis that HMF-related carcinogenicity may be mediated by its reactive
      metabolite SMF.

PMID- 19382818
TI  - Community-based interventions to promote increased physical activity: a primer.
AB  - Current recommendations, based on an abundance of empirical data documenting the
      impact of physical activity (PA) on preventing morbidity and mortality associated
      with common chronic diseases, indicate that adults should accumulate 30 minutes
      of moderate-intensity PA > or =5 days per week. However, worldwide rates of PA
      remain low, indicating a great need for large-scale implementation of evidence
      based PA interventions. We briefly present practical aspects of intervention
      planning, implementation and evaluation within common community settings. The
      first stage of intervention planning is formative research, which allows for a
      better understanding of the elements needed for a successful intervention.
      Partnering with community settings (schools, worksites, faith-based organizations
      and healthcare organizations) offers many benefits and the opportunity to reach
      specific populations. Setting-based approaches allow for multilevel strategies,
      ranging from individual-based programmes and educational initiatives to physical
      and social environmental changes. Various settings such as healthcare, worksite,
      and school- and community-based settings are discussed. Intervention delivery
      methods and strategies can range, depending on the population and setting
      targeted, from small-group approaches to mediated methods (e.g. print, telephone,
      electronic). The final phase of intervention planning and implementation is
      evaluation. Several objective and subjective methods of PA assessment are
      available to determine the effectiveness of the intervention. We have highlighted
      the need for process evaluation of intervention implementation to provide
      valuable information for the dissemination and sustainability of successful
      interventions. Although there are numerous considerations for the design,
      implementation, assessment and evaluation of PA interventions, the potential for
      positive impact on the overall health of the public indicates the necessity for
      programmes designed to increase PA.

PMID- 19382819
TI  - A pharmacoeconomic analysis of compliance gains on antipsychotic medications.
AB  - BACKGROUND: Compliance among patients with schizophrenia is typically poor.
      Consequently, treatments that are equally efficacious under trial-based
      conditions but face different compliance rates in clinical practice (e.g. due to
      adverse-effect profile, ease of use, reputation) may have differences in
      effectiveness not observed during trials. This study analyses the impact of
      differences in compliance with atypical antipsychotics using a pharmacoeconomic
      discrete-event simulation (DES) model, adapted to the Swedish treatment setting.
      METHODS: An existing 5-year DES model was adapted to reflect a Swedish setting;
      the analysis was conducted from a third-party payer perspective, with only direct
      costs included. The two treatment arms were identical except for percentage of
      compliant patients. Non-compliant patients experienced shorter time between
      relapses and had inferior symptom control than their compliant counterparts. The
      difference in compliance rates was varied from 0% to 15%, and incremental costs
      and effects were recorded and analysed. RESULTS: With a 5%, 10% and 15%
      difference in compliance rate, incremental effects increased to 0.021, 0.037 and
      0.062, respectively, while generating cost savings of Swedish kronor (SEK)31 500,
      SEK62 000 and SEK104 500, respectively (SEK9.25 = 1, Euro year 2007 values).
      Hence, each percentage point of compliance gain is predicted to roughly result in
      a cost saving of SEK6000 and a QALY gain of 0.004. On average, the model predicts
      that, with a 15% increase in compliance, 0.5 relapses are prevented, the average
      Positive And Negative Syndrome Scale (PANSS) score decreases by 3.3 points and
      patients spend 22 fewer days in hospital over 5 years. CONCLUSIONS: The DES model
      predicts that increases in compliance may lead to considerable cost savings and
      health improvements. Therefore, when determining the cost effectiveness of a new
      antipsychotic, efficacy rates from clinical trials should not be taken at face
      value, but should be interpreted in tandem with expectations concerning
      compliance, in light of product characteristics such as adverse effects. These
      results further suggest that efforts to improve compliance among patients with
      schizophrenia are expected to prove cost effective if compliance gains and the
      resulting health improvements and cost savings are in balance with the additional
      costs.

PMID- 19382820
TI  - Cost-effectiveness analysis of vaccination against rotavirus with RIX4414 in
      France.
AB  - BACKGROUND: It is estimated that annually 300 000 cases of rotavirus-induced
      gastroenteritis (RVGE) occur in children aged up to 5 years in France. A two-dose
      vaccine against rotavirus infection (RIX4414; Rotarix, GlaxoSmithKline), has been
      shown to be highly effective against severe RVGE. OBJECTIVE: This study evaluated
      the cost effectiveness of general vaccination against rotavirus using RIX4414 in
      France. METHODS: A Markov model simulated RVGE events and the associated outcomes
      and costs relating to general vaccination of infants against rotavirus infection
      using RIX4414 (Rotarix) in a birth cohort of children aged up to 5 years in
      France with a combined adjustment for age distribution with the seasonality of
      the infection. Costs and outcomes were estimated from a limited societal
      perspective, including direct medical costs paid out of pocket or by third-party
      payers, as well as the proportion of direct medical costs reimbursed by the
      health authorities. Indirect costs were not included in the base-case analysis.
      The primary outcome measure was the incremental cost per QALY. RESULTS:
      Vaccination with RIX4414 incurred an incremental cost of 44 583 Euro per QALY at
      a public price of 57 Euro per vaccine dose. Univariate sensitivity analyses
      showed that the parameters with the largest influence on the results were the
      transition probabilities of severe diarrhoea, seeking medical advice and
      emergency visits, utility scores of diarrhoea (mild) in children and infants, and
      the discount rate for benefits. Probabilistic multivariate sensitivity analysis
      confirmed these results. The acceptability curve indicated that 94% of the
      results were under an informal threshold of 50 000 Euro per QALY. Comparing our
      results with those of a recently published study using pooled data for two
      rotavirus vaccine products in France, the main differences are explained by
      differences in model structure and in data input values. They include a different
      age distribution of the infection, shorter duration of the at-risk period (3
      years instead of 5 years), different vaccine efficacy, different unit cost data,
      different disease duration, and different disutility values for the health states
      in the model. There is a need for agreed standards to improve comparability of
      results from different studies. CONCLUSIONS: The results demonstrate that a
      generalized vaccination strategy with RIX4414 would be cost effective in France
      from a limited societal perspective, depending on the baseline assumptions for
      disease progression and on utility scores selected.

PMID- 19382821
TI  - Does extending health insurance coverage to the uninsured improve population
      health outcomes?
AB  - BACKGROUND: An ongoing debate exists about whether the US should adopt a
      universal health insurance programme. Much of the debate has focused on programme
      implementation and cost, with relatively little attention to benefits for social
      welfare. OBJECTIVE: To estimate the effect on US population health outcomes,
      measured by mortality, of extending private health insurance to the uninsured,
      and to obtain a rough estimate of the aggregate economic benefits of extending
      insurance coverage to the uninsured. METHOD: We use state-level panel data for
      all 50 states for the period 1990-2000 to estimate a health insurance augmented,
      aggregate health production function for the US. An instrumental variables fixed
      effects estimator is used to account for confounding variables and reverse
      causation from health status to insurance coverage. Several observed factors,
      such as income, education, unemployment, cigarette and alcohol consumption and
      population demographic characteristics are included to control for potential
      confounding variables that vary across both states and time. RESULTS: The results
      indicate a negative relationship between private insurance and mortality, thus
      suggesting that extending insurance to the uninsured population would result in
      an improvement in population health outcomes. The estimate of the marginal effect
      of insurance coverage indicates that a 10% increase in the population-insured
      rate of a state reduces mortality by 1.69-1.92%. Using data for the year 2003, we
      calculate that extending private insurance coverage to the entire uninsured
      population in the US would save over 75 000 lives annually and may yield annual
      net benefits to the nation in excess of $US400 billion. CONCLUSION: This analysis
      suggests that extending health insurance coverage through the private market to
      the 46 million Americans without health insurance may well produce large social
      economic benefits for the nation as a whole.

PMID- 19382822
TI  - Cost-effectiveness analysis of entecavir versus lamivudine in the first-line
      treatment of Australian patients with chronic hepatitis B.
AB  - BACKGROUND: Chronic hepatitis B (CHB) virus infection is a major global
      healthcare problem. The recent introduction of entecavir in Australia for the
      treatment of CHB patients in the naive treatment setting has triggered
      significant optimism with regards to improved clinical outcomes for CHB patients.
      OBJECTIVE: To estimate, from an Australian healthcare perspective, the cost
      effectiveness of entecavir 0.5 mg/day versus lamivudine 100 mg/day in the
      treatment of CHB patients naive to nucleos(t)ide therapy. METHODS: A cost-utility
      analysis to project the clinical and economic outcomes associated with CHB
      disease and treatment was conducted by developing two decision-tree models
      specific to hepatitis B e antigen-positive (HBeAg+ve) and HBeAg-ve CHB patient
      subsets. This analysis was constructed using the Australian payer perspective of
      direct costs and outcomes, with indirect medical costs and lost productivity not
      being included. The study population comprised a hypothetical cohort of 1000
      antiviral treatment-naive CHB patients who received either entecavir 0.5 mg/day
      or lamivudine 100 mg/day at model entry. The population of patients used in this
      analysis was representative of those patients likely to receive initial antiviral
      therapy in clinical practice in Australia. The long-term cost effectiveness of
      entecavir compared with lamivudine in the first-line treatment of CHB patients
      was expressed as an incremental cost per life-year gained (LYG) or QALY gained.
      RESULTS: Results revealed that the availability of entecavir 0.5 mg/day as part
      of the Australian hepatologist's treatment armamentarium should result in
      significantly lower future rates of compensated cirrhosis (CC), decompensated
      cirrhosis (DC), and hepatocellular carcinoma (HCC) events (i.e. 54 fewer cases of
      CC, seven fewer cases of DC, and 20 fewer cases of HCC over the model's timeframe
      for HBeAg+ve CHB patients, and 69 fewer cases of CC, eight fewer cases of DC and
      25 fewer cases of HCC over the model's timeframe for HBeAg-ve CHB patients).
      Compared with lamivudine 100 mg/day, entecavir 0.5 mg/day generated an estimated
      incremental cost per LYG of Australian dollars ($A, year 2006 values) 5046 and an
      estimated incremental cost per QALY of $A5952 in the HBeAg+ve CHB patient
      population, an estimated incremental cost per LYG of $A7063 and an estimated
      incremental cost per QALY of $A8003 in the HBeAg-ve CHB patient population, and
      an overall estimated incremental cost per LYG of $A5853 and an estimated
      incremental cost per QALY of $A6772 in the general CHB population. CONCLUSION:
      The availability of entecavir in Australian clinical practice should make long
      term suppression of hepatitis B virus replication increasingly attainable,
      resulting in fewer CHB sequelae, at an acceptable financial cost.

PMID- 19382823
TI  - Environmental footprint of pharmaceuticals: the significance of factors beyond
      direct excretion to sewers.
AB  - The combined excretion of active pharmaceutical ingredients (APIs) via urine and
      feces is considered the primary route by which APIs from human pharmaceuticals
      enter the environment. Disposal of unwanted, leftover medications by flushing
      into sewers has been considered a secondary route-one that does not contribute
      substantially to overall environmental loadings. The present study presents the
      first comprehensive examination of secondary routes of API release to the
      environment and for direct but unintentional human exposure. These include
      bathing, washing, and laundering, all of which release APIs remaining on the skin
      from the use of high-content dermal applications or from excretion to the skin
      via sweating, and disposal of unused and partially used high-content devices.
      Also discussed are the health hazards associated with: partially used devices,
      medication disposal practices of consumers, and interpersonal dermal transfer of
      API residues. Understanding these secondary routes is important from the
      perspective of pollution prevention, because actions can be designed more easily
      for reducing the environmental impact of APIs compared with the route of direct
      excretion (via urine and feces), for reducing the incidence of unintentional and
      purposeful poisonings of humans and pets, and for improving the quality and cost
      effectiveness of health care. Overall, unintentional exposure to APIs for humans
      via these routes is possibly more important than exposure to trace residues
      recycled from the environment in drinking water or foods.

PMID- 19382824
TI  - Parasites of the deepwater sculpin (Myoxocephalus thompsonii) across its Canadian
      range.
AB  - Deepwater sculpin (Myoxocephalus thompsonii) were collected from 19 lakes across
      the species' distribution in Canada and examined for parasites. Six helminth
      species (Crepidostomum farionis, Bothriocephalus cuspidatus, Proteocephalus sp.,
      Cyathocephalus truncatus, Raphidascaris acus, and Echinorhynchus salmonis), 1
      crustacean species (Ergasilus nerkae), and 1 molluscan species (glochidia)
      parasitized these hosts. Crepidostomum farionis, Proteocephalus sp., R. acus, E.
      nerkae, and the glochidia represent new parasite records for this host species.
      Overall parasite prevalence was 78.0% while mean intensity was 6.1 +/- 7.1 SD.
      Bothriocephalus cuspidatus was the most prevalent parasite and was recorded from
      62.2% of the deepwater sculpin and found in 17 of the 19 lakes. The low
      productivity habitat of this host limits the parasites available for
      transmission, and the infra- and component communities were generally species
      poor. With the exception of the Proteocephalus sp., all of the helminth parasites
      recovered have been reported as adults in lake trout (Salvelinus namaycush) or
      burbot (Lota lota), suggesting that, in the lakes where they occur, deepwater
      sculpin may play an important role in energetic transfer and parasitic
      transmission to higher trophic levels.

PMID- 19382825
TI  - Apparent absence of Parahaemoproteus lophortyx and other hematozoa in North
      Florida populations of bobwhite quail (Colinus virginianus).
AB  - Parahaemoproteus lophortyx (formerly Haemoproteus lophortyx) is known to infect
      populations of bobwhite quail (Colinus virginianus) in California and to lead to
      considerable mortalities in these birds. Populations of bobwhite quail in Florida
      have never been surveyed for the presence of this parasite. The goal of this
      study was to determine whether P. lophortyx is present in populations of bobwhite
      quail in north Florida. To achieve this goal, blood was drawn from 294 bobwhite
      quail from 4 study sites in north Florida from 19 June 2007 to 1 August 2007.
      Blood smears were made, stained with Giemsa, and examined under x1,000
      magnification for the presence of Parahaemoproteus lophortyx. No gametocytes were
      noted in any of the blood smears. Thirty randomly chosen samples were examined
      via polymerase chain reaction (PCR). This procedure may detect parasitemias too
      low to detect by microscopy. No PCR-positive samples were detected, however,
      adding support to the absence of hematozoa in Florida populations of bobwhite
      quail.

PMID- 19382827
TI  - Education to improve cancer care in rural South Australia.
AB  - INTRODUCTION: Cancer management follows the overall trend of rural health
      disparities, with higher incidence rates of preventable cancers and lower
      survival rates in rural Australia. Cancer prevention and management has been
      identified as a priority area and Cancer Australia has funded a variety of
      innovations throughout Australia. The Rural Chemotherapy Mentoring Program (RCMP)
      forms part of this drive to improve access to chemotherapy for rural based cancer
      sufferers in South Australia (SA). The key strategy of this program was the
      provision of opportunities for rural health clinicians (nurses and GPs) to
      enhance their knowledge and skills in the delivery of chemotherapy and cancer
      care through clinical placements at metropolitan oncology units. The RCMP
      enrolled 43 current SA rural clinicians (five GPs and 38 nurses). This evaluation
      was undertaken at the end of RCMP's initial 18 months. It considered how those
      involved in the RCMP perceived development and delivery of the RCMP, identifying
      key aspects of the program that were successful. This report emphasises lessons
      learnt which may be of relevance more widely in the development of other rural
      health professional education. METHODS: The evaluation used a mixed method
      approach, designed to accommodate different perspectives from the health
      professionals with different roles in the program. Quantitative and qualitative
      questionnaire data from clinician participants, their employers, and providers of
      education at metropolitan cancer units, were supplemented with qualitative
      interview data from these sample groups and from the program's steering
      committee. The analysis used interpretative methods to examine the key strengths,
      limitations and the potential for future development of the program. RESULTS: The
      vast majority of participants, employers, providers of training and the steering
      committee representatives expressed high levels of overall satisfaction about
      their involvement in RCMP. A clear identifiable need for increased knowledge and
      skills in cancer care was expressed by rural clinical participants pre-clinical
      placement. Technical aspects of the delivery of some chemotherapy protocols and
      the steps in safely preparing patients to receive chemotherapy were key areas
      where respondents lacked confidence prior to their clinical placement. Post
      placement self-evaluation data highlighted improvements in participants'
      understandings and confidence about chemotherapy, and cancer care knowledge.
      Participants and their employers identified change in specific work activities
      resulting from their new knowledge. The program's limitations were identified.
      CONCLUSIONS: Knowledge acquisition was a key to the success of the program, and
      the transfer of experience between rural and urban based clinicians was an
      important aspect of this. Generalisable recommendations for further improvement
      of the RCMP include: (1) clearly define and articulate a precise learning
      objective of the program; (2) involve staff who will directly deliver mentoring
      in planning of the program; (3) allow time in the planning phase to resolve
      complex indemnity issues across workplaces; and (4) provide funding for a
      dedicated trainer (preferably a staff member within the unit) to supervise
      placements in busy urban oncology clinics.

PMID- 19382828
TI  - Survey of a videoconference community of professional development for rural and
      urban nurses.
AB  - INTRODUCTION: Videoconferencing technology has the potential to increase
      opportunities for healthcare professionals in rural and remote areas to access
      continuing professional development. This research used a quantitative approach
      to an evaluation of the effectiveness of videoconferencing technology in the
      development of a community of professional development. METHOD: In 2008 a
      videoconference symposia was held across four sites in New South Wales,
      Australia. A survey developed and adapted from an existing model of online
      teaching and learning was completed by 55% (n = 56) of attendees. RESULTS: Survey
      findings revealed that successful aspects of the videoconference community
      included 'being welcoming and providing useful information', as partially or
      fully agreed by all respondents. Less successful aspects of the community
      included ease of use, with 44.6% (n = 25) either disagreeing or partially
      disagreeing that the videoconference was easy to use; reliability, with 33.9% (n
      = 37) either disagreeing or partially disagreeing that the community platform was
      reliable; and knowledge construction, with 69.1% (n = 38) identifying that they
      only took information and did not add ideas or content. CONCLUSION: The findings
      indicate that although the videoconference ran effectively with the experience of
      minor technical difficulties, respondents demonstrated more of a passive role
      than constructive in their development of new knowledge, despite the promotion of
      an interactive environment.

PMID- 19382829
TI  - Developing competencies for remote and rural senior allied health professionals
      in Western Australia.
AB  - Competency frameworks are an increasingly popular clinical governance,
      performance management, and professional development tool in health care.
      However, to date there is a dearth of information relating to competencies for
      allied health professionals (AHPs) working in remote and rural environments. This
      project aimed to develop a competency framework for senior level AHPs across a
      core of allied health professions in remote and rural Western Australia. The
      framework was designed to be used by individual AHPs to identify areas of
      professional proficiency and weakness, by staff managing senior AHPs when
      undertaking performance development processes, and by an organisation to identify
      common areas of need among disciplines that can be addressed through targeted
      support strategies.

PMID- 19382831
TI  - Phototherapy in peripheral nerve injury for muscle preservation and nerve
      regeneration.

PMID- 19382830
TI  - Dynamic 3D culture promotes spontaneous embryonic stem cell differentiation in
      vitro.
AB  - Spontaneous in vitro differentiation of mouse embryonic stem cells (mESC) is
      promoted by a dynamic, three-dimensional (3D), tissue-density perfusion technique
      with continuous medium perfusion and exchange in a novel four-compartment,
      interwoven capillary bioreactor. We compared ectodermal, endodermal, and
      mesodermal immunoreactive tissue structures formed by mESC at culture day 10 with
      mouse fetal tissue development at gestational day E9.5. The results show that the
      bioreactor cultures more closely resemble mouse fetal tissue development at
      gestational day E9.5 than control mESC cultured in Petri dishes.

PMID- 19382832
TI  - Implantation of low-level laser irradiated mesenchymal stem cells into the
      infarcted rat heart is associated with reduction in infarct size and enhanced
      angiogenesis.
AB  - OBJECTIVE: The aim of the present study was to evaluate the possible beneficial
      effects of implantation of laser-irradiated mesenchymal stem cells (MSCs) into
      the infarcted rat heart. BACKGROUND DATA: It was demonstrated that low-level
      laser therapy (LLLT) upregulates cytoprotective factors in ischemic tissues.
      MATERIALS AND METHODS: MSCs were isolated from rat bone marrow and grown in
      culture. The cells were laser irradiated with a Ga-Al-As laser (810 nm
      wavelength), labeled with 5-bromo-2'deoxyuridine (BrdU), and then implanted into
      infarcted rat hearts. Non-irradiated cells were similarly labeled and acted as
      controls. Hearts were excised 3 wk later and cells were stained for BrdU and c
      kit immunoreactivity. RESULTS: Infarcted hearts that were implanted with laser
      treated cells showed a significant reduction of 53% in infarct size compared to
      hearts that were implanted with non-laser-treated cells. The hearts implanted
      with laser-treated cells prior to implantation demonstrated a 5- and 6.3-fold
      significant increase in cell density that positively immunoreacted to BrdU and c
      kit, respectively, as compared to hearts implanted with non-laser-treated cells.
      A significantly 1.4- and 2-fold higher level of angiogenesis and vascular
      endothelial growth factor, respectively, were observed in infarcted hearts that
      were implanted with laser-treated cells compared to non-laser-treated implanted
      cells. CONCLUSION: The findings of the present study provide the first evidence
      that LLLT can significantly increase survival and/or proliferation of MSCs post
      implantation into the ischemic/infarcted heart, followed by a marked reduction of
      scarring and enhanced angiogenesis. The mechanisms associated with this
      phenomenon remain to be elucidated in further studies.

PMID- 19382833
TI  - Thermal and morphological effects of the pulsed Nd:YAG laser on root canal
      surfaces.
AB  - OBJECTIVE: To investigate the sequential thermal and morphological effects of the
      pulsed Nd:YAG laser on root canal surfaces. BACKGROUND DATA: Effectiveness and
      safety are two critical aspects of laser application for root canal
      instrumentation. To date, few studies have synchronously focused on the efficacy
      of root canal cleanliness and thermal changes in root surfaces irradiated by the
      Nd:YAG laser. MATERIALS AND METHODS: Single-root human premolars (n = 144) were
      sectioned at the cementoenamel junction. The root canals were instrumented and
      divided into three groups: group 1 (15 Hz), group 2 (20 Hz), and group 3 (15 Hz
      with black ink). Each group was divided into eight subgroups according to the
      laser power settings used. The temperature elevations of the apical and coronal
      root surfaces were measured with a thermocouple measurement system during laser
      irradiation. Then the roots were bisected longitudinally and examined with the
      scanning electron microscope. RESULTS: There was a positive correlation between
      laser energy level and temperature elevation of the root surfaces of all three
      groups. The temperature elevation in group 3 was the highest, while that in group
      1 was the lowest at all power settings. More strikingly, with increasing laser
      power and frequency, there were corresponding morphological changes seen in the
      root canal wall, such as removal of the smear layer and melting and
      recrystallization of the dentin. At 2.0 W, the temperature elevations seen in all
      three groups were within the biologically tolerable thermal limit, but efficient
      removal of the smear layer was achieved only in groups 2 and 3. Additionally, the
      thermal and morphological changes seen at the apical third of the root were
      greater than those seen at the coronal third. CONCLUSION: This study provides
      useful information on the choice of appropriate energy parameters to use during
      application of pulsed Nd:YAG energy for root canal therapy.

PMID- 19382834
TI  - Autofluorescence of breast tissues: evaluation of discriminating algorithms for
      diagnosis of normal, benign, and malignant conditions.
AB  - OBJECTIVE: We evaluated different discriminating algorithms for classifying laser
      induced fluorescence spectra of normal, benign, and malignant breast tissues that
      were obtained with 325-nm excitation. BACKGROUND DATA: Mammography and
      histopathology are the conventional gold standard methods of screening and
      diagnosis of breast cancers, respectively. The former is prone to a high rate of
      false-positive results and poses the risk of repeated exposure to ionizing
      radiation, whereas the latter suffers from subjective interpretations of
      morphological features. Thus the development of a more reliable detection and
      screening methodology is of great interest to those practicing breast cancer
      management. Several studies have demonstrated the efficacy of optical
      spectroscopy in diagnosing cancer and other biomedical applications. MATERIALS
      AND METHODS: Autofluorescence spectra of normal, benign, and malignant breast
      tissues, with 325-nm excitation, were recorded. The data were subjected to
      diverse discriminating algorithms ranging from intensities and ratios of curve
      resolved bands to principal components analysis (PCA)-derived parameters.
      RESULTS: Intensity plots of collagen and NADPH, two known fluorescent biomarkers,
      yielded accurate classification of the different tissue types. PCA was carried
      out on both unsupervised and supervised methods, and both approaches yielded
      accurate classification. In the case of the supervised classification, the
      developed standard sets were verified and evaluated. The limit test approach
      provided unambiguous and objective classification, and this method also has the
      advantage of being user-friendly, so untrained personnel can directly compare
      unknown spectra against standard sets to make diagnoses instantly, objectively,
      and unambiguously. CONCLUSION: The results obtained in this study further support
      the efficacy of 325-nm-induced autofluorescence, and demonstrate the suitability
      of limit test analysis as a means of objectively and unambiguously classifying
      breast tissues.

PMID- 19382835
TI  - Effect of Er:YAG laser parameters on ablation capacity and morphology of primary
      enamel.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ablation capacity of
      different energies and pulse repetition rates of Er:YAG laser energy on primary
      molar enamel, by assessing mass loss and by analyzing the surface morphology with
      scanning electron microscopy. BACKGROUND DATA: Previous studies have demonstrated
      the capacity of the Er:YAG laser to ablate enamel substrate. METHODS: Forty-two
      sound primary molars were bisected in a mesiodistal direction. The enamel
      surfaces were flattened and their initial mass (in milligrams) was obtained. An
      area of 4 mm(2) was delimited. The specimens were randomly assigned to 12 groups
      according to the combination of energy (160, 200, 250, and 300 mJ) and pulse
      repetition rate (2, 3, and 4 Hz). Er:YAG laser irradiation was performed on each
      specimen for 20 sec. After irradiation, the final mass was obtained and specimens
      were prepared for examination with scanning electron microscopy. The data
      obtained by subtracting the final mass from the initial mass were statistically
      analyzed using ANOVA and the Tukey test (p < 0.05). RESULTS: The pulse repetition
      rate of 4 Hz provided greater mass loss, different from that seen with 2 Hz, and
      similar to that seen with 3 Hz. The energy level of 300 mJ resulted in greater
      mass loss, similar to that seen with 200 and 250 mJ. Scanning electron
      photomicrographs showed that there was non-selective enamel removal, with fused
      and cracked areas in all specimens. CONCLUSION: The parameters of 200 mJ and 2 Hz
      produced a good ablation rate with fewer surface alterations in primary molar
      enamel.

PMID- 19382836
TI  - Evaluation of laparoscopic liver resection with two different Nd:YAG lasers for
      future use in a high-field open MRI.
AB  - OBJECTIVE: Laparoscopic liver surgery is a safe and feasible technique for the
      treatment of benign and malignant liver tumors and has been well established at
      many specialized centers. Many different techniques of tissue dissection have
      been developed. As an alternative various lasers have been applied to
      conventional liver resections. Laser surgery is potentially beneficial for
      laparoscopic liver resection, allowing parenchymal dissection and vessel
      coagulation. A second advantage is the non-ferromagnetic character of this
      instrument, which facilitates magnetic resonance (MR)-guided interventions. In
      this study two different Nd:YAG lasers were evaluated for laparoscopic liver
      resection in a porcine model. In other studies this technique will be transferred
      into an interventional open MRI for image-guided liver resection. MATERIALS AND
      METHODS: We used 1064-nm and 1318-nm Nd:YAG lasers for laparoscopic wedge,
      segmental, and left lateral liver lobe resection. During the intervention blood
      loss, resection time, and cardiopulmonary parameters were quantified. The
      resected specimen underwent histomorphometric analysis for thermal tissue
      effects, including parenchymal carbonization, necrosis, and vessel coagulation.
      RESULTS: The resected volume showed a positive correlation with intraoperative
      blood loss, which increased from wedge resection (245 mL, SD +/- 71 mL) and
      segment resection (325 mL), to left lateral resection (455 mL). Total parenchymal
      dissection was slightly faster with the 1064-nm Nd:YAG laser (9 min, SD +/- 5
      min) compared with the 1318-nm Nd:YAG laser (11 min, SD +/- 4 min). Thermally
      induced vessel sealing was shown for liver veins and arteries to a maximum
      diameter of 2 mm. CONCLUSION: Laparoscopic liver resection with both Nd:YAG
      lasers is a safe and feasible technique, allowing parenchymal dissection and
      coagulation. The 1064-nm Nd:YAG laser showed increased tissue damage with more
      effective coagulation capability than the 1318-nm Nd:YAG laser. Because of its
      non-ferromagnetic characteristics, laser-based laparoscopic liver resection is
      potentially useful for image-guided surgery in an open MRI.

PMID- 19382837
TI  - Low-level laser therapy increases transforming growth factor-beta2 expression and
      induces apoptosis of epithelial cells during the tissue repair process.
AB  - BACKGROUND DATA: Low-level laser therapy (LLLT) has been reported to modulate the
      healing of wounds by inducing an increase in mitotic activity, fibroblast number,
      synthesis of collagen, and neovascularization. OBJECTIVE: In the present study we
      evaluated the effect of LLLT on expression of TGF-beta(2), an immunosuppressive
      cytokine, at the site of tissue repair, using an experimental rat model to study
      cutaneous wound healing. In addition, we also investigated the presence of
      apoptotic cells in epithelial and connective tissue. MATERIALS AND METHODS:
      Thirty male Wistar rats were divided into two groups: group 1, which was
      subjected to surgical skin wounds only (n = 15), and group 2, which was subjected
      to surgical skin wounds followed by LLLT (n = 15). In group 2, the LLLT was given
      with these parameters: 15 mW of power, a dose of 3.8 J/cm(2), for 15 sec for
      three applications. At 10 d post-surgery and laser application the animals were
      sacrificed with an overdose of anesthetic and tissue samples from the wounds were
      submitted to immunohistochemistry and in-situ detection of apoptosis. RESULTS:
      Most of the inflammatory cells and fibroblasts were TGF-beta(2)-positive, and
      many apoptotic epithelial cells and fibroblasts were seen in the tissue samples
      from the LLLT-treated animals. However, a few apoptotic epithelial cells and
      fibroblasts were also seen in the samples obtained from control animals.
      CONCLUSION: Our results indicate that LLLT may be an important inducer of
      apoptosis during the process of tissue repair. In addition, we demonstrated that
      LLTT has an immunomodulatory effect on TGF-beta(2) expression at sites of wound
      healing.

PMID- 19382838
TI  - The efficacy of facial skin cancer treatment with high-energy pulsed neodymium
      and Nd:YAG lasers.
AB  - OBJECTIVE: The aim of this study was to assess the curative and cosmetic efficacy
      of treatment for facial skin cancer using neodymium laser irradiation. BACKGROUND
      DATA: Due to the complex anatomy of the area, therapy for facial skin cancer is
      difficult. MATERIALS AND METHODS: Laser irradiation was used for the treatment of
      3461 patients with 3624 facial skin cancer lesions of stages T(1-2)N(0)M(0:) 3346
      basal cell skin cancers, 188 limited basal cell skin cancer recurrences, and 90
      squamous cell skin cancers. Pulsed neodymium (Nd) and Nd:YAG lasers were used as
      the energy sources. The patients were followed-up from 3 mo to 5 y or more.
      RESULTS: Patients with basal cell skin cancer treated by irradiation with the Nd
      laser developed recurrences in 1.8% of cases, and patients treated with the
      Nd:YAG laser had a recurrence rate of 2.5%. Recurrences following treatment for
      basal cell skin cancer, and those of squamous cell skin cancer, after irradiation
      with the Nd laser appeared in 3.7% and 4.4% of patients, respectively. Overall,
      the frequency of facial skin cancer recurrences after treatment with laser
      irradiation was 2.1% of all the irradiated tumors. CONCLUSION: Neodymium laser
      irradiation is an effective method to treat facial skin cancer of stages T(1
      2)N(0)M(0), and results in acceptable cosmetic results.

PMID- 19382839
TI  - The temperature changes in the pulp chamber during cavity preparation with the
      Er:YAG laser using a very short pulse.
AB  - OBJECTIVE: The aim of this study was to examine the temperature changes in the
      pulp chamber during cavity preparation with the Er:YAG laser (2940 nm) with a
      very short pulse (VSP). MATERIALS AND METHODS: Nine groups of 10 intact molars
      each were used. One root of each sample was amputated and a thermocouple was
      inserted into the chamber. Class V cavity preparation in enamel was performed,
      and then preparation was performed in dentine. The enamel was lased with 400,
      360, and 320 mJ in contact mode using a VSP with a duration of 100 microsec. The
      diameter of the fiber tip was 950 microm. Frequencies of 10, 12, and 15 Hz were
      used, and the total time of irradiation was 10 sec. The dentine was irradiated
      with 340, 280, and 200 mJ at 10, 8, and 5 Hz for 7 sec. Cooling was done with a
      water spray (73 psi and 50 mL/min). The differences were tested by MANOVA and the
      Bonferroni post hoc test. RESULTS: The highest rise in temperature in the pulp
      was achieved after enamel irradiation with 400 mJ and 15 Hz (1.99 +/- 0.28
      degrees C), and the lowest was after irradiation with 320 mJ and 10 Hz (0.70 +/-
      0.18 degrees C). In dentine the highest temperature increase was achieved with
      340 mJ and 10 Hz (1.37 +/- 0.42 degrees C), and the lowest was with 200 mJ and 5
      Hz (0.43 +/- 0.18 degrees C). Two-way analysis of both enamel and dentine showed
      that the influence of energy on temperature increase was stronger than that of
      frequency. CONCLUSION: Cavity preparation with an Er:YAG laser using VSP mode in
      vitro did not cause significant increases in temperature in the pulp chamber of
      human molars.

PMID- 19382840
TI  - Photodynamic therapy can be effective as a treatment for herpes simplex labialis.
AB  - BACKGROUND DATA AND OBJECTIVE: Herpes is a common infectious disease that is
      caused by human herpesviruses. Several treatments have been proposed, but none of
      them prevent reactivation of the virus. This article describes the use of
      photodynamic therapy (PDT) as a treatment for herpes lesions, and reports on four
      cases. MATERIALS AND METHODS: PDT was used as an adjuvant therapy for the
      treatment of herpes labialis in four patients. A special type of 0.01% (m/V) of
      methylene blue solution was applied to the vesicular stage of herpesviral disease
      and the lesions were irradiated with laser energy (wavelength 660 nm, energy
      density 120 J/cm(2), output power of 40 mW, 2 min per point, 4.8 J of
      energy/point, at four points). After 24 h the patients returned and phototherapy
      was repeated with the same equipment, this time with 3.8 J/cm(2) and 15 mW, for a
      total dose of 0.6 J. The same procedure was repeated 72 h and 1 wk later.
      RESULTS: Treatment with low-level laser therapy can be considered as an option in
      the treatment of herpes labialis, and decreases the frequency of vesicle
      recurrence and provides comfort for patients. No significant acute side effects
      were noted and the lesions healed rapidly. CONCLUSION: Treatment of herpes
      labialis with PDT was effective, had no side effects, and when associated with
      laser phototherapy, accelerated the healing process.

PMID- 19382841
TI  - Removal of a discal cyst using a percutaneous endoscopic interlaminar approach: a
      case report.
AB  - Here we report on a percutaneous endoscopic interlaminar approach using a side
      firing Ho:YAG laser for the treatment of lumbar discal cyst with a successful
      clinical outcome. A 27-year-old man presented with left gluteal and leg pain due
      to a discal cyst at the L5-S1 level. A percutaneous endoscopic interlaminar
      approach was used to remove the cyst, achieving complete decompression of the
      nerve root. The symptoms were relieved and the patient was discharged the next
      day. A percutaneous endoscopic interlaminar approach using a side-firing Ho:YAG
      laser appears to be a suitable alternative treatment for selected patients with
      lumbar discal cysts.

PMID- 19382843
TI  - Photomedicine and LLLT literature watch.

PMID- 19382844
TI  - Generation of rat monoclonal antibodies specific for Ad4BP/SF-1.
AB  - Ad4BP/SF-1 (adrenal4 binding protein/steroidogenic factor-1[NR5A1]) is an
      essential nuclear receptor required for animal reproduction and endocrine
      regulation. The present study reports on monoclonal antibodies (MAbs) directed
      against mouse Ad4BP/SF-1, which were produced by the hybridization of mouse
      myeloma cells with lymph node cells of an immunized rat. The produced MAbs
      reacted with both recombinant and endogenous Ad4BP/SF-1. These MAbs will be
      useful in immunolocalization and immunoblotting experiments conducted on
      different tissue types to determine the levels of expression of Ad4BP/SF-1
      throughout development, as well as further analyses of the biological function
      and cellular dynamics of this protein.

PMID- 19382845
TI  - Preparation and characterization of a novel chimeric antibody against human CD40
      with the potential to inhibit Daudi cell proliferation.
AB  - 5C11, a murine monoclonal antibody with a high specificity for human CD40
      molecule, is a promising candidate for cancer targeting therapy. We have
      therefore attempted to construct a humanized antibody of 5C11 to minimize its
      immunogenicity for potential clinical use. A chimeric version of 5C11 (ch-5C11)
      was generated by transferring these mouse variable regions onto a human
      framework. This chimeric antibody retained reactivity to human CD40. In vitro, ch
      5C11 could effectively inhibit B lymphoma Daudi cell proliferation, suggesting
      that it might have the potential to be developed for future clinical use.

PMID- 19382846
TI  - Generation and utilization of anti-drug monoclonal antibodies for screening of 36
      drug users by dot-ELISA.
AB  - In this study, we prepared monoclonal antibodies against morphine, methadone,
      babital, methamphetamine, and phencyclidine, then developed a dot-ELISA method by
      such antibodies to test their efficacy in clinical application and the screening
      of urine samples. It was found that there were 36 narcotics-positive drug users,
      including 28 morphine positive, six methamphetamine positive, and two positive
      for both. All the results were confirmed by commercial drug testing kits.

PMID- 19382852
TI  - Density-dependent male mating harassment, female resistance, and male mimicry.
AB  - Genetic variation in female resistance and tolerance to male mating harassment
      can affect the outcome of sexually antagonistic mating interactions. We
      investigated female mating rates and male mating harassment in natural
      populations of a damselfly (Ischnura elegans). This damselfly species has a
      heritable sex-limited polymorphism in females, where one of the morphs is a male
      mimic (androchrome females). The three female morphs differ in mating rates, and
      these differences are stable across populations and years. However, the degree of
      premating resistance toward male mating attempts varied across generations and
      populations. Male mating harassment of the female morphs changed in a density
      dependent fashion, suggesting that male mate preferences are plastic and vary
      with the different morph densities. We quantified morph differences in male
      mating harassment and female fecundity, using path analysis and structural
      equation modeling. We found variation between the morphs in the fitness
      consequences of mating, with the fecundity of one of the nonmimetic morphs
      declining with increasing male mating harassment. However, androchrome females
      had lower overall fecundity, presumably reflecting a cost of male mimicry.
      Density-dependent male mating harassment on the morphs and fecundity costs of
      male mimicry are thus likely to contribute to the maintenance of this female
      polymorphism.

PMID- 19382853
TI  - CD14-negative isolation enhances chondrogenesis in synovial fibroblasts.
AB  - Synovial membrane has been shown to contain mesenchymal stem cells. We
      hypothesized that an enriched population of synovial fibroblasts would undergo
      chondrogenic differentiation and secrete cartilage extracellular matrix to a
      greater extent than would a mixed synovial cell population (MSCP). The optimum
      doses of transforming growth factor beta 1 (TGF-beta1) and insulin-like growth
      factor 1 (IGF-1) for chondrogenesis were investigated. CD14-negative isolation
      was used to obtain a porcine cell population enriched in type-B synovial
      fibroblasts (SFB) from an MSCP. The positive cell surface markers in SFB were
      CD90, CD44, and cadherin-11. SFB and MSCP were cultured in the presence of 20
      ng/mL TGF-beta1 for 7 days, and SFB were demonstrated to have higher chondrogenic
      potential. Further dose-response studies were carried out using the SFB cells and
      several doses of TGF-beta1 (2, 10, 20, and 40 ng/mL) and/or IGF-1 (1, 10, 100,
      and 500 ng/mL) for 14 days. TGF-beta1 supplementation was essential for
      chondrogenesis and prevention of cell death, whereas IGF-1 did not have a
      significant effect on the SFB cell number or glycosaminoglycan production. This
      study demonstrates that the CD14-negative isolation yields an enhanced cell
      population SFB that is more potent than MSCP as a cell source for cartilage
      tissue engineering.

PMID- 19382854
TI  - Substrate-induced assembly of fibronectin into networks: influence of surface
      chemistry and effect on osteoblast adhesion.
AB  - The influence of surface chemistry-substrates with controlled surface density of 
      OH groups-on fibronectin (FN) conformation and distribution is directly observed
      by atomic force microscopy (AFM). FN fibrillogenesis, which is known to be a
      process triggered by interaction with integrins, is shown in our case to be
      induced by the substrate (in absence of cells), which is able to enhance FN-FN
      interactions leading to the formation of a protein network on the material
      surface. This phenomenon depends both on surface chemistry and protein
      concentration. The level of the FN fibrillogenesis was quantified by calculating
      the fractal dimension of the adsorbed protein from image analysis of the AFM
      results. The total amount of adsorbed FN is obtained by making use of a
      methodology that employs Western blotting combined with image analysis of the
      corresponding protein bands, with the lowest sensitivity threshold equal to 15 ng
      of adsorbed protein. Further, FN adsorption is correlated to human osteoblast
      adhesion through morphology and actin cytoskeleton formation. Actin
      polymerization is in need of the formation of the protein network on the
      substrate's surface. Cell morphology is more rounded (as quantified by
      calculating the circularity of the cells by image analysis) when the degree of FN
      fibrillogenesis on the substrate is lower.

PMID- 19382857
TI  - Telethinking with Karen S. Rheuban, M.D. Interview by Vicki Glaser.

PMID- 19382858
TI  - Innovative programs in telemedicine. European Institute of Telesurgery
      (EITS)/WeBSurg.

PMID- 19382859
TI  - Remote monitoring of asthma.

PMID- 19382860
TI  - Healthcare via cell phones: a systematic review.
AB  - Regular care and informational support are helpful in improving disease-related
      health outcomes. Communication technologies can help in providing such care and
      support. The purpose of this study was to evaluate the empirical evidence related
      to the role of cell phones and text messaging interventions in improving health
      outcomes and processes of care. Scientific literature was searched to identify
      controlled studies evaluating cell phone voice and text message interventions to
      provide care and disease management support. Searches identified 25 studies that
      evaluated cell phone voice and text messaging interventions, with 20 randomized
      controlled trials and 5 controlled studies. Nineteen studies assessed outcomes of
      care and six assessed processes of care. Selected studies included 38,060
      participants with 10,374 adults and 27,686 children. They covered 12 clinical
      areas and took place in 13 countries. Frequency of message delivery ranged from 5
      times per day for diabetes and smoking cessation support to once a week for
      advice on how to overcome barriers and maintain regular physical activity.
      Significant improvements were noted in compliance with medicine taking, asthma
      symptoms, HbA1C, stress levels, smoking quit rates, and self-efficacy. Process
      improvements were reported in lower failed appointments, quicker diagnosis and
      treatment, and improved teaching and training. Cost per text message was provided
      by two studies. The findings that enhancing standard care with reminders, disease
      monitoring and management, and education through cell phone voice and short
      message service can help improve health outcomes and care processes have
      implications for both patients and providers.

PMID- 19382861
TI  - Lifelink: 3G-based mobile telemedicine system.
AB  - Current wired telemedicine systems encounter difficulties when implemented in
      archipelagic developing countries because of the high cost of fixed
      infrastructure. In this research, we devised Lifelink, a mobile real-time
      telemonitoring and diagnostic facility to command and control remote medical
      devices through mobile phones. The whole process is phone-based, effectively
      freeing offsite medical specialists from stationary monitoring consoles and
      endowing the system with the potential to increase the number participating
      consultants. The electrocardiogram (ECG) readings are analyzed using a detrended
      fluctuation technique and classified into pathological cases using an unassisted
      K-means clustering algorithm. We analyzed 30 batches of 2-hour ECG signals taken
      from cardiac patients (20 males, 10 females, mean age 46.7 years) with pre
      diagnosed pathologies. The method successfully categorized the 30 subjects
      without user intervention into the following cases: normal (at 86.7% accuracy),
      congestive heart failure (86.7%), and atrial fibrillation (80.0%). The synergy of
      mobile monitoring and fluctuation analysis presents a powerful platform to reach
      remote, underserved communities with poor or nonexistent wired communication
      structures. It is likely to be essential in the development of new mobile
      diagnostic and prognostic measures.

PMID- 19382862
TI  - The effects of redesigning the IDEATel architecture on glucose uploads.
AB  - The objective of this evaluation was to determine the effect of redesigning the
      Informatics for Diabetes Education and Telemedicine (IDEATel) telemedicine
      architecture on the average upload delay and on the average number of glucose
      uploads to a central database. These two measures positively influence our
      ability to deliver timely and accurate patient care to the study population. The
      redesign was also undertaken to improve the patients' experience in using the
      system and thereby increase the frequency and timeliness of their self-monitoring
      behavior. Using the total number of glucose uploads, we compared the delay in
      glucose upload times according to the type of home telemedicine unit the study
      participants used and the region where the participants lived. The participants
      were Medicare beneficiaries with diabetes living in medically underserved
      neighborhoods in New York City and rural Upstate New York. The populations in
      these two regions differed considerably in terms of ethnicity, language spoken
      (Spanish, English), and education level. Participants who had Generation 2 (Gen
      2) (mean = 10.75, SD +/- 7.96) home telemedicine units had significantly shorter
      upload delay times (p < 0.001) as measured in days than those participants with
      Generation 1 (Gen 1) (mean = 22.44, SD +/- 11.18) and those who were upgraded
      from Gen 1 (mean = 20.67, SD +/- 8.85) to Gen 2 (mean = 14.93, SD +/- 9.37).
      Additionally, the delay was significantly shorter for participants living upstate
      (mean = 24.14 days, SD +/- 11.95 days) than downstate (mean = 15.30 days, SD +/-
      7.87 days), t (975) = 13.98, p < 0.01. The system redesign made a significant
      impact in reducing glucose upload delays of IDEATel participants. However, upload
      delays were significantly impacted by the region where the participants resided.

PMID- 19382863
TI  - Exploring technology impacts of Healthcare 2.0 initiatives.
AB  - As Internet access proliferates and technology becomes more accessible, the
      number of people online has been increasing. Web 2.0 and the social computing
      phenomena (such as Facebook, Friendster, Flickr, YouTube, Blogger, and MySpace)
      are creating a new reality on the Web: Users are changing from consumers of Web
      available information and resources to generators of information and content.
      Moving beyond telehealth and Web sites, the push toward Personal Health Records
      has emerged as a new option for patients to take control of their medical data
      and to become active participants in the push toward widespread digitized
      healthcare. There is minimal research on the impact of Web 2.0 in healthcare.
      This paper reviews the changing patient-physician relationship in the Healthcare
      2.0 environment, explores the technological challenges, and highlights areas for
      research.

PMID- 19382865
TI  - Factors determining the use of personal digital assistants among physicians.
AB  - The objective of this study was to examine the factors that might influence the
      use of personal digital assistant devices (PDAs) by physicians for assistance in
      the delivery of their routine patient care. An Internet-based single-institution
      survey was done of internal medicine resident physicians. None of the baseline
      demographic characteristics measured were associated with whether PDAs were being
      used or not by resident physicians in patient care. Resident physicians who used
      their PDAs for medical purposes perceived more benefits associated with the use
      of PDAs, and fewer barriers, than did those who did not own a PDA, or owned one
      but did not use it for medical purposes. Among regular users of PDAs for medical
      purposes, greater frequency of use in patient care was associated with more
      positive perceptions of the devices. Some associations were also found between
      residents' self-reported standardized test scores and the type of information
      resources being used on their device. Similar to previous studies, the majority
      of those in this cohort owned PDAs, and most of those who owned one used it for
      assistance in delivery of their patient care. It is concluded that users of PDAs
      for medical purposes differ from nonusers in certain attitudes and opinions, and
      standardized test scores may correlate with different patterns of use. These
      results may be useful in helping medical leaders overcome barriers to more full
      adoption of PDAs as a tool for effective patient care.

PMID- 19382864
TI  - The SUMMA Project: a feasibility study on telemedicine in selected Italian areas.
AB  - Telemedicine is achieving relevant clinical importance in rural areas in the
      management of patients. The Second opinion Unificata per Medici di Medicina
      generAle (SUMMA) Project was designed to evaluate the feasibility of a joint
      telemedicine service application across general practitioners and clinical
      specialists in Italy. The secondary objective of the study included the
      comparison of telemedicine with the routine general practitioners' approach and a
      cost-effectiveness evaluation. One hundred and thirty-five general practitioners
      from Lombardy, Molise, and Valle d'Aosta were enrolled. An ad hoc questionnaire
      was used to evaluate the feasibility, approval, efficacy, and satisfaction of
      telemedicine among the general practitioners. Ninety-three general practitioners
      used the telemedicine consultation (responders) for a total of 1,396 calls (1,264
      for cardiology, 65 for dermatology, 32 for diabetology, 22 for rheumatology, and
      13 for pneumology). In cardiology, telemedicine was used to address all problems
      without further action in 733 cases (61%). Ninety-eight percent of responders
      indicate satisfaction with telemedicine. The cost of telemedicine in our study
      was estimated to be 25.36 Euros/contact. In conclusion, the SUMMA Project
      demonstrated for the first time clinically the effectiveness of second-opinion
      consultation by general practitioners and therefore fulfilling the actual needs
      in areas usually managed by the National Health System.

PMID- 19382866
TI  - Incorporating telehealth into primary care resident outpatient training.
AB  - Research is yet to fully examine the utility and effectiveness of telehealth in
      primary care resident ambulatory training. This study examined the attitudes of
      preceptors, residents, and nurses on (1) the impact of telehealth on healthcare;
      (2) the impact of telehealth on the work activity of resident clinics; (3) the
      impact of telehealth on resident training in the outpatient setting; and (4) the
      impact of telehealth on relationships. There were three focus groups, one each of
      preceptors (N = 5), residents (N = 10), nurses (N = 7). Eight focus group themes
      evolved regarding the use of telehealth in the resident clinic: (1) impact on
      patient/provider relationships; (2) consistent with the values of those using
      telehealth; (3) logistics; (4) reduces patient transfers; (5) appropriate level
      of care; (6) reimbursement concerns; (7) psychological risk; and (8) impact on
      resident/attending relationships. Though as yet not generalizable, results of
      this pilot study suggest that there is general acceptability of telehealth in
      ambulatory resident training settings, but there is concern about the impact that
      telehealth may have on relationships, logistics, finances, and the need to see
      patients face-to-face when there is greater complexity.

PMID- 19382867
TI  - Evaluation of a novel ambulatory device for screening of sleep apnea.
AB  - The gold standard for diagnosis of obstructive sleep apnea (OSA) is the sleep
      laboratory polysomnography, which is technically demanding, labor-intensive, and
      time-consuming. Thus, screening of large undiagnosed population for OSA may be
      cost efficient only by means of ambulatory devices suitable for home recordings.
      The aim of our study was to evaluate the diagnostic and technical reliability of
      a novel ambulatory device (APV2, Remote Analysis Oy) introduced for sleep apnea
      diagnostics. APV2 records breathing movements, nasal and oral air flow, position,
      snore, blood oxygen saturation, and heart rate. The evaluation was done by
      comparing 10 simultaneous polygraphic recordings with APV2 and with commonly used
      clinical reference instrumentation (Embla, Embla Co.) at a sleep laboratory.
      Furthermore, the technical reliability of measurements was evaluated by analyzing
      the fraction of clinical APV2 and Embletta (Embla Co.) home recordings (n = 149
      and n = 169, respectively) that were technically of diagnostically unacceptable
      quality. Similar diagnostic sensitivity in detecting OSA was found with the APV2
      compared to the simultaneous reference recording with the Embla. Apnea-hypopnea
      indices and oxygen desaturation indices, recorded with APV2 and Embla, were
      closely correlated (r = 0.996-0.997, p < 0.0001). The quality of 90.0% of home
      recordings with APV2 was technically perfect and 96.0% of recordings were of
      diagnostically acceptable quality. As a comparison, the clinical evaluation of a
      widely used ambulatory polygraphy device (Embletta) showed that 77.2% of home
      recordings were technically perfect and 80.8% of recordings were diagnostically
      acceptable. In conclusion, the novel device was found clinically applicable,
      technically reliable, and sensitive for the diagnostics of OSA.

PMID- 19382868
TI  - Toward the design of a wearable system for contact thermography in telemedicine.
AB  - Thermal imaging of the skin has been used for several decades for monitoring of
      temperature distribution of human skin for the detection of thermal abnormalities
      indicating pathologies (malignancies, inflammation, infection, and vascular,
      dermatological, and rheumatic disorders). Literature has shown that to detect and
      monitor the thermal abnormalities related to pathologic conditions, there is a
      need to extend acquisition over 8, 12, 16, or 24 hours. A wearable device is
      strongly needed in contact thermography to reach the objective of long-term
      monitoring of contact thermography, especially in telemedicine applications. A
      wearable system has been designed and constructed that allows the continuous
      thermographic monitoring of a skin region at the point of affixation. Measurement
      allowed by this system is direct and not hampered by the influence of the
      environment--as with IR thermography--nor by the geometry of skin surface
      (curvatures, roughness) thanks to the flexible adaptation of the sensing head to
      the surface. The validation of the system embedded in a pilot preliminary
      telemedicine application was successful. The next step will be the wide focusing
      and adaptation to telemedicine clinical applications to assess the response to
      the chemotherapy and tune the therapy at home of the breast cancer or the
      response to the inflammation care.

PMID- 19382869
TI  - Toward the design of a wearable system for fall-risk detection in
      telerehabilitation.
AB  - Telemedicine represents a valid aid in rehabilitation process. A remote therapist
      in a telerehabilitation program could monitor daily motion activity and assign
      motion-rehabilitation tools on the basis of the fall risk. However, one problem
      is detection of the fall risk itself. Web-based video-camera images alone do not
      help the remote assessment of the fall risk using the most commonly used
      qualitative tests based on visual observation. A novel wearable system to assess
      fall risk in telerehabilitation has been proposed based on an Inertial
      Measurement Unit and a medical protocol. It provides a score in four levels (1:
      no fall risk; 4: major fall risk). The telemedicine tool is integrated to the
      Global System for Mobile communication (GSM) net. Each component of the wearable
      system has been designed and integrated. Each component in the system has been
      tested individually and in a closed loop. One subject was monitored in a
      telemedicine link. The test showed a high degree of acceptance. The tool will be
      furnished to subjects along with a homecare device for daily routine monitoring
      of motion activity and could eventually be integrated with other systems designed
      to monitor other physiological parameters along with different aids and
      monitoring tools.

PMID- 19382871
TI  - Multiple channel bridges for spinal cord injury: cellular characterization of
      host response.
AB  - Bridges for treatment of the injured spinal cord must stabilize the injury site
      to prevent secondary damage and create a permissive environment that promotes
      regeneration. The host response to the bridge is central to creating a permissive
      environment, as the cell types that respond to the injury have the potential to
      secrete both stimulatory and inhibitory factors. We investigated multiple channel
      bridges for spinal cord regeneration and correlated the bridge structure to cell
      infiltration and axonal elongation. Poly(lactide-co-glycolide) bridges were
      fabricated by a gas foaming/particulate leaching process. Channels within the
      bridge had diameters of 150 or 250 microm, and the main body of the bridge was
      highly porous with a controllable pore size. Upon implantation in a rat spinal
      cord hemisection site, cells infiltrated into the bridge pores and channels, with
      the pore size influencing the rate of infiltration. The pores had significant
      cell infiltration, including fibroblasts, macrophages, S-100beta-positive cells,
      and endothelial cells. The channels of the bridge were completely infiltrated
      with cells, which had aligned axially, and consisted primarily of fibroblasts, S
      100beta-positive cells, and endothelial cells. Reactive astrocytes were observed
      primarily outside of the bridge, and staining for chondroitin sulfate
      proteoglycans was decreased in the region surrounding the bridge relative to
      studies without bridges. Neurofilament staining revealed a preferential growth of
      the neural fibers within the bridge channels relative to the pores. Multiple
      channel bridges capable of supporting cellular infiltration, creating a
      permissive environment, and directing the growth of neural fibers have potential
      for promoting and directing spinal cord regeneration.

PMID- 19382872
TI  - Perlecan domain IV peptide stimulates salivary gland cell assembly in vitro.
AB  - Treatment of xerostomia would benefit from development of a functional
      implantable artificial salivary gland. Salivary gland tissue from surgical
      patients was assessed by histology and immunohistochemistry to establish the
      phenotype of normal salivary gland cells including the native basement membranes.
      Ductal and acinar cells were identified in tissue and cultured cells from
      dispersed tissue. High levels of laminin and perlecan/HSPG2 (heparan sulfate
      proteoglycan 2) were noted in basement membranes, and perlecan also was secreted
      and organized by cultured acinar populations, which formed lobular structures
      that mimicked intact glands when cultured on Matrigel or a bioactive peptide
      derived from domain IV of perlecan. On either matrix, large acini-like lobular
      structures grew and formed connections between the lobes. alpha-Amylase secretion
      was confirmed by staining and activity assay. Biomarkers, including tight
      junction protein E-cadherin and water channel protein aquaporin 5 found in
      tissue, were expressed in cultured acinar cells. Cells cultured on Matrigel or
      domain IV of perlecan peptide organized stress fibers and activated focal
      adhesion kinase. We report a novel technique to isolate acinar cells from human
      salivary gland and identify a human peptide sequence in perlecan that triggers
      differentiation of salivary gland cells into self-assembling acini-like
      structures that express essential biomarkers and which secrete alpha-amylase.

PMID- 19382873
TI  - A novel scaffold with longitudinally oriented microchannels promotes peripheral
      nerve regeneration.
AB  - Longitudinally oriented microstructures are essential for a nerve scaffold to
      promote significant regeneration of injured peripheral axons across nerve gaps.
      Extensive attention has been devoted to develop scaffolds with inner structures
      mimicking the nerve-guiding basal lamina microchannels in autografts. However, to
      date, little information has been obtained about scaffolds with similar inner
      microstructures, and the efficacy of such scaffolds in bridging peripheral nerve
      gaps in vivo has never been examined. In the present study, we describe a novel
      nerve-guiding collagen-chitosan (CCH) scaffold with inner dimensions resembling
      the basal lamina microchannels of normal nerves. The scaffold has a number of
      structural advantages, including longitudinally orientated microchannels and
      extensive interconnected pores between the parallel microchannels. We evaluated
      the efficacy of the CCH scaffold to bridge a 15-mm-long sciatic nerve defect in
      rats using a combination of morphological and functional techniques. The in vivo
      animal study showed that the CCH scaffold achieved nerve regeneration and
      functional recovery equivalent to that of an autograft, without the exogenous
      delivery of regenerative agents or cell transplantation. These findings
      demonstrate that CCH scaffolds may be used as alternatives to nerve autografts
      for peripheral nerve regeneration.

PMID- 19382874
TI  - HIV-1 superinfection in an HIV-2-infected woman with subsequent control of HIV-1
      plasma viremia.
AB  - A human immunodeficiency virus type 2 (HIV-2)-infected woman experienced
      asymptomatic superinfection with HIV-1 subtype AG. She did not have cross
      neutralizing autologous HIV-1 antibodies before and shortly after HIV-1
      superinfection. This evidence supports a mechanism other than cross-neutralizing
      antibodies for the mild course of HIV-1 infection in this woman.

PMID- 19382875
TI  - Isolation and differentiation of chicken mesenchymal stem cells from bone marrow.
AB  - Mesenchymal stem cells (MSCs) are multipotent progenitor cells found in bone
      marrow that have the capacity of differentiating into bone, cartilage, fat,
      muscle, and other tissues. Chicken MSCs were isolated from 1- to 14-day-old
      chickens. Microscopically, the cultured cells showed morphology resembling
      fibroblasts and divided actively. Chicken MSCs expressed the transcription
      factors PouV, Sox2, and Nanog, which have been shown to be critical for stem cell
      self-renewal and pluripotency. The multilineage differentiation potential of
      chicken MSCs was revealed by their ability to undergo adipogenic, osteogenic, and
      chondrogenic differentiation. Like mammalian MSCs, chicken MSCs also had
      immunoregulatory activity and inhibited in vitro mitogenic response of T cells.
      The inhibition of mitogenic response of T cells correlated with the production of
      nitric oxide (NO) in cultures containing MSCs and T cells. Our data show for the
      first time that MSCs can be isolated from postnatal chicken bone marrow and these
      cells are capable of in vitro multiplication and multilineage differentiation,
      thus making them a suitable model in the field of stem cell research.

PMID- 19382877
TI  - Toward a construct definition of informed consent comprehension.
AB  - VARIATION IN HOW INFORMED CONSENT comprehension tests have been developed may be
      largely due to the absence of a standardized construct definition. Developing a
      construct definition would provide a standardized framework for determining how
      an instrument should be constructed, implemented, interpreted, and applied.
      Therefore, we utilized the Delphi consensus approach with an international expert
      panel (N = 19) to gather knowledge, opinions and eventually consensus for a
      construct definition. Expert consensus was achieved after three revision cycles.
      While acknowledging that there are limitations to this study, it nonetheless
      should be considered as a step toward standardization of a construct definition
      of informed consent comprehension.

PMID- 19382878
TI  - The biomedical ethics ontology proposal: excellent aims, questionable methods.
AB  - KOEPSELL ET AL. (2009) DESCRIBE AN IDEAL biomedical ethics committee environment
      with efficiencies such as electronic and universal application forms and consent
      templates, automated decision-trees, and broad sharing of data. However, it is
      unclear that a biomedical ethics ontology (BMEO) is necessary or even helpful in
      establishing such environment. Two features of any applied ontology are
      particularly problematic in establishing a useful BMEO: (1) an ontology is a
      description of a domain of reality; and (2) the description is subject to ongoing
      revision as it is developed through open processes, e.g., the use of a wiki. A
      BMEO would need to address two main kinds of entities, regulatory definitions and
      ethical concepts, and is ill-suited to both. Regulatory definitions are fiats and
      ought to be adopted verbatim to ensure compliance, but in such cases we do not
      need the assistance of ontologists, and their modes of working (constant revision
      within open wiki-based communities) might even be counterproductive. Ethical
      concepts within pluralistic societies are social constructs, not a priori
      concepts or biological natural kinds, and the prospects of generating intuitive
      definitions that enjoy broad acceptance across cultures and institutional
      settings are slim. In making these arguments, I draw from the writings of leading
      applied ontologists and Koepsell et al.'s own proof of concept.

PMID- 19382879
TI  - Anonymous self-evaluation of performance by ethics board members: a pilot study.
AB  - EVALUATING THE EFFECTIVENESS OF A Reserch Ethics Committee or Institutional
      Review Board (IRB) continues to be a difficult task. There are limited data that
      examine the perceptions of members of IRBs about their own performance or methods
      that would allow comparison among IRB panels at a single institution or between
      institutions. We piloted an anonymous survey instrument that examined members'
      attitudes about the efficiency, procedures and outcomes of IRB meetings and
      developed a process for presentation and discussion of these results with panel
      members. This quality improvement process was initially completed with one panel,
      and then replicated with two other IRB panels at one institution. This allowed
      comparison of perceived IRB performance across panels at a single institution.
      Further research is required to determine the association between IRB members'
      perception of performance and other measures of IRB effectiveness and to examine
      the perceived performance of IRBs by other research stakeholders.

PMID- 19382880
TI  - Measurement and prediction of the rate and extent of drug delivery into and
      through the skin.
AB  - Skin diseases are prevalent and can significantly affect quality of life.
      Empirical mathematical models retrospectively analyse data to predict skin
      permeation from the physico-chemical properties of drugs. Quantitative structure
      permeability relationships are discussed, along with alternatives to linear
      modelling. Mechanistic mathematical models derived from first principles are also
      considered. Further, in vitro experiments allow predictions to be made using
      suitable membranes (cultured cell lines or excised skins). In vivo methods to
      assess (trans)dermal drug delivery aim to minimise clinical studies, especially
      to determine whether formulations are bioequivalent. Microdialysis is discussed,
      together with the FDA-approved skin blanching (pharmacodynamic) assay for
      corticosteroids. The progress made with the tape stripping methodology is
      reviewed. Two distinct strategies have emerged, the first where the total amount
      of drug in the stratum corneum (SC) at one uptake and one clearance time are
      compared; and the second which generates drug permeation profiles across the SC,
      and allows dermatopharmacokinetic parameters to be derived.

PMID- 19382881
TI  - Poly(alkylcyanoacrylate) nanoparticles for enhanced delivery of therapeutics - is
      there real potential?
AB  - The properties inherent in poly(alkylcyanoacrylate) (PACA) nanoparticles, such as
      biocompatibility and biodegradability of the polymer, a simple preparation
      process and particularly the entrapment of bioactives, specifically proteins and
      peptides, have sparked extensive interest in these nanoparticles as drug delivery
      systems. Research has focused on the oral route of administration, however
      ocular, transdermal and delivery across the blood-brain barrier have also been
      investigated. Despite numerous promising studies, no formulation with this
      colloidal carrier has been marketed to date. A number of factors have been
      identified as interfering with the reproducibility of in vitro and in vivo
      results, which impedes the comparison of the plethora of experiments done with
      PACA nanoparticles. This review will highlight the challenges and opportunities
      of using PACA nanoparticles as drug delivery systems, including polymerisation
      mechanisms and templates, entrapment, release, nanoparticle uptake and toxicity.
      In vitro and in vivo studies, as well as possible surface modifications for
      targeted delivery in the human field and veterinary applications of PACA
      nanoparticles are reviewed. Emphasis will be placed on microemulsions as
      templates for the preparation of PACA nanoparticles and oral delivery of proteins
      and peptides.

PMID- 19382882
TI  - New drug delivery strategies for improved Parkinson's disease therapy.
AB  - Increasing interest has been addressed toward the introduction of new therapeutic
      approaches to obtaining continuous dopaminergic stimulation (CDS). The goal of
      this therapeutic strategy is to reduce the occurrence and severity of L-DOPA (LD)
      associated motor fluctuations and dyskinesia, and provide good long-term safety
      and tolerability. CDS can be achieved by the administration of oral dopamine (DA)
      agonists with a long half-life, transdermal or subcutaneous delivery of DA
      agonists, or intestinal LD infusion. To allow higher concentrations of LD to
      reach the brain and to reduce peripheral side effects, the therapeutic approach
      provides the concomitant administration of LD, carbidopa and entacapone that have
      been developed in tablet form, standard LD/carbidopa, LD/benserazide,
      LD/entacapone, LD/tolcapone associations or long-acting controlled release
      formulations, LD/carbidopa and LD/benserazide. Alternatively to solid
      formulations, LD/carbidopa liquid forms have been developed. Furthermore, the
      authors examine a series of new LD codrugs and non-dopaminergic drugs for
      Parkinson's disease treatment, together with a variety of experimental delivery
      strategies including transdermal therapeutic systems, liposomes, solid lipid
      nanoparticles and biocompatible microparticles. This review provides an overview
      of progress in anti-Parkinson therapy, mainly focused on delivery strategies and
      codrug approach for treatment of this neurological disorder.

PMID- 19382884
TI  - The role of the disulfide group in disulfide-based polymeric gene carriers.
AB  - BACKGROUND: An essential prerequisite for successful gene therapy is the
      development of safe and efficient gene delivery carriers. For this purpose,
      cationic polymers have been widely studied as non-viral carriers, but they
      generally suffer from low transfection efficiency and/or high cytotoxicity. To
      address these problems, disulfide-based cationic polymers have been designed as
      intelligent gene carriers that are capable of inducing highly efficient gene
      transfection with low cytotoxicity. OBJECTIVE: The present review discusses the
      effects of the disulfide linker on the gene delivery properties of cationic
      polymers in relation to various gene delivery barriers. METHODS: The literature
      regarding the gene delivery barriers encountered by polymeric gene delivery is
      reviewed and discussed in relation to the presence of the disulfide moiety in
      these gene carriers. CONCLUSIONS: The presence of disulfide linkages in cationic
      polymers can in many aspects favorably influence the gene delivery properties,
      such as increasing DNA binding ability, enabling de-shielding of 'stealth' (PEG)
      groups, fine-tuning of the buffer capacity for enhanced endosomal escape,
      improving carrier-unpacking and decreasing cytotoxicity. Therefore, disulfide
      based cationic polymers are promising candidates for the next generation of non
      viral carriers.

PMID- 19382885
TI  - Multiple-pulse drug delivery systems: setting a new paradigm for infectious
      disease therapy.
AB  - BACKGROUND: Pulsatile drug delivery of actives based on the body's biological
      rhythms came into sight as a novel and emerging concept in the field of drug
      delivery. The concept of late has given birth to another field of research worth
      exploring: multiple-pulse drug delivery. OBJECTIVE: Delivering a drug in multiple
      pulses has been applied to antibiotics for effective and patient compliant drug
      delivery. Delivering antibiotics in divided pulses results in better annihilation
      of microbes, as it prevents them going into a resistant/dormant stage and
      developing biological tolerance. The concept appears to have potential, and on 16
      March 2009 MiddleBrook Pharmaceuticals, Inc. will launch the first of such once
      daily product based on their proprietary pulsatile drug delivery technology,
      PULSYS. METHODS: This review focuses on the rationale, possible strategies and
      technologies employed for multiple-pulse delivery, as well as current status and
      future trends. CONCLUSION: The concept is in its infancy and promises great
      potential in the fight against microbial resistance; many approved formulations
      based on similar approaches with new and improved therapeutic paradigms are
      anticipated in the near future.

PMID- 19382883
TI  - Prodrug approaches to improving the oral absorption of antiviral nucleotide
      analogues.
AB  - Nucleotide analogues have been well accepted as therapeutic agents active against
      a number of viruses. However, their use as antiviral agents is limited by the
      need for phosphorylation by endogenous enzymes, and if the analogue is orally
      administered, by low bioavailability due to the presence of an ionizable diacid
      group. To circumvent these limitations, a number of prodrug approaches have been
      proposed. The ideal prodrug achieves delivery of a parent drug by attachment of a
      non-toxic moiety that is stable during transport and delivery, but is readily
      cleaved to release the parent drug once at the target. Here, a brief overview of
      several promising prodrug strategies currently under development is given.

PMID- 19382886
TI  - An interview with Garry Nolan, Ph.D. by Glaser Vicki.

PMID- 19382888
TI  - The current status of drug discovery against the human kinome.
AB  - Protein kinases are important targets in drug discovery programs aimed at
      treating many devastating diseases, including cancer, autoimmune disorders,
      diabetes, and neurological disorders. Most "classical" drug discovery efforts
      employ rational drug design methods based upon structural information to identify
      compounds targeting the enzyme catalytic domain. Novel information on kinase
      biology is opening up other approaches in the design of selective inhibitors that
      may provide more subtle modulation of these drug discovery targets. The
      identification of such modulators requires adoption of a new generation of high
      throughput screening techniques. These approaches will allow measurement of
      conformational changes in kinases, as well as protein-protein interactions via
      assessment of functional responses such as cellular translocation. Therefore a
      range of novel techniques, together with the understanding that numerous "orphan"
      kinases will provide targets for therapeutics, suggests that a new era of kinase
      therapies is rapidly emerging.

PMID- 19382889
TI  - High-throughput screening compatible cell-based assay for interrogating activated
      notch signaling.
AB  - Aberrant Notch pathway function is associated with a wide array of developmental
      disorders, cancers, and neurodegenerative diseases. Thus, strategies to modulate
      Notch signaling may facilitate therapeutic intervention. Ligand binding to Notch
      receptors at the cell surface results in a series of cleavage events that release
      Notch intracellular domain (NICD) fragments that translocate to the nucleus where
      they function as transcriptional activators of downstream transcriptional
      programs. We have developed a cell-based assay that can be used to screen for
      modulators of NICD signaling by engineering HeLa cervical cancer cells with a
      Notch response element driving beta-lactamase (BLA) reporter gene expression
      along with a tetracycline-inducible NICD expression system. Induction of NICD
      expression leads to increased BLA reporter activity that can be knocked down
      using NICD-specific RNA interference as well as RNA interference against
      endogenous components of the NICD transactivation complex. Profiling of 19 known
      compounds in this assay identified several previously undescribed modulators of
      NICD signaling. The Wnt pathway inhibitor ICG-001 antagonized NICD signaling,
      whereas the histone deacetylase inhibitor suberoylanilide hydroxamic acid, the
      heat shock protein 90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin, and the
      dual phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin inhibitor
      PI-103 each further activated the NICD-driven reporter activity. The AKT
      inhibitor triciribine and the PI3K inhibitor GDC-0941 also resulted in the
      enhanced reporter activity, strongly implicating a role for the PI3K/AKT pathway
      in regulating NICD signaling. Together this cell-based assay system provides a
      sensitive, quantitative readout for NICD signaling that is amenable to high
      throughput screening for NICD pathway modulators.

PMID- 19382890
TI  - Bioassays for estrogenic activity: development and validation of estrogen
      receptor (ERalpha/ERbeta) and breast cancer proliferation bioassays to measure
      serum estrogenic activity in clinical studies.
AB  - Standard estrogenic prodrugs such as estradiol valerate (E2V) and increasingly
      popular phytoestrogen formulations are commonly prescribed to improve menopausal
      health. These drugs are metabolized to numerous bioactive compounds, known or
      unknown, which may exert combinatorial estrogenic effects in vivo. The aim of
      this study is to develop and validate estrogen receptor (ER) alpha/ERbeta
      reporter gene and MCF-7 breast cancer cell proliferation bioassays to quantify
      serum estrogenic activities in a clinical trial setting. We measured changes in
      serum estrogenicity following ingestion of E2V and compared this to mass
      spectrometric measurements of its bioactive metabolites, estrone and 17beta
      stradiol. ERalpha bioactivity of the 192 serum samples correlated well (R = 79%)
      with 17beta-estradiol levels, and adding estrone improved R to 0.83 (likelihood
      ratio test, P < 0.0001), suggesting that the ERalpha assay reflects summated
      activity of compounds in serum. ERbeta correlated moderately (R = 0.52) with
      estrone and 17beta-estradiol, with an estrone/17beta-estradiol coefficient ratio
      that was twice that of ERalpha, indicating estrone was more active on a molar
      basis in the ERbeta assay. Unlike the ERalpha and ERbeta bioassays, MCF-7 cell
      proliferation was driven by 17beta-estradiol, and addition of estrone did not
      increase the predictive value of the model, suggesting that the driver or drivers
      for breast cancer cell proliferation were not the same as for ERalpha and ERbeta
      transactivation. In contrast, a decoction of the traditional Chinese medicinal
      herb Epimedium pubescens did not induce significant changes in estrogenic
      bioactivity over baseline. These data indicate that ERalpha/ERbeta reporter gene
      and MCF-7 breast cancer cell proliferation bioassays reflect different aspects of
      estrogenic activity and that these assays suggest that the Epimedium formulation
      tested is unlikely to exert significant estrogenic effects in humans.

PMID- 19382891
TI  - AlphaLISA immunoassay platform- the "no-wash" high-throughput alternative to
      ELISA.

PMID- 19382893
TI  - Pathogen recognition in the innate immune response.
AB  - Immunity against microbial pathogens primarily depends on the recognition of
      pathogen components by innate receptors expressed on immune and non-immune cells.
      Innate receptors are evolutionarily conserved germ-line-encoded proteins and
      include TLRs (Toll-like receptors), RLRs [RIG-I (retinoic acid-inducible gene-I)
      like receptors] and NLRs (Nod-like receptors). These receptors recognize
      pathogens or pathogen-derived products in different cellular compartments, such
      as the plasma membrane, the endosomes or the cytoplasm, and induce the expression
      of cytokines, chemokines and co-stimulatory molecules to eliminate pathogens and
      instruct pathogen-specific adaptive immune responses. In the present review, we
      will discuss the recent progress in the study of pathogen recognition by TLRs,
      RLRs and NLRs and their signalling pathways.

PMID- 19382894
TI  - Metabolic modulation and cellular therapy of cardiac dysfunction and failure.
AB  - At present the prevalence of heart failure rises along with aging of the
      population. Current heart failure therapeutic options are directed towards
      disease prevention via neurohormonal antagonism (beta-blockers, angiotensin
      converting enzyme inhibitors and/or angiotensin receptor blockers and aldosterone
      antagonists), symptomatic treatment with diuretics and digitalis and use of
      biventricular pacing and defibrillators in a special subset of patients. Despite
      these therapies and device interventions heart failure remains a progressive
      disease with high mortality and morbidity rates. The number of patients who
      survive to develop advanced heart failure is increasing. These patients require
      new therapeutic strategies. In this review two of emerging therapies in the
      treatment of heart failure are discussed: metabolic modulation and cellular
      therapy. Metabolic modulation aims to optimize the myocardial energy utilization
      via shifting the substrate utilization from free fatty acids to glucose. Cellular
      therapy on the other hand has the goal to achieve true cardiac regeneration. We
      review the experimental data that support these strategies as well as the
      available pharmacological agents for metabolic modulation and clinical
      application of cellular therapy.

PMID- 19382895
TI  - Cardiac renewing: interstitial Cajal-like cells nurse cardiomyocyte progenitors
      in epicardial stem cell niches.
AB  - Recent studies suggested that various cell lineages exist within the
      subepicardium and we supposed that this area could host cardiac stem cell niches
      (CSCNs). Using transmission electron microscopy, we have found at least 10 types
      of cells coexisting in the subepicardium of normal adult mice: adipocytes,
      fibroblasts, Schwann cells and nerve fibres, isolated smooth muscle cells, mast
      cells, macrophages, lymphocytes, interstitial Cajal-like cells (ICLCs) and
      cardiomyocytes progenitors (CMPs). The latter cells, sited in the area of origin
      of coronary arteries and aorta, showed typical features of either very immature
      or developing cardiomyocytes. Some of these cells were connected to each other to
      form columns surrounded by a basal lamina and embedded in a cellular network made
      by ICLCs. Complex intercellular communication occurs between the ICLCs and CMPs
      through electron-dense nanostructures or through shed vesicles. We provide here
      for the first time the ultrastructural description of CSCN in the adult mice
      myocardium, mainly containing ICLCs and CMPs. The existence of resident CMPs in
      different developmental stages proves that cardiac renewing is a continuous
      process. We suggest that ICLCs might act as supporting nurse cells of the cardiac
      niches and may be responsible for activation, commitment and migration of the
      stem cells out of the niches. Briefly, not only resident cardiac stem cells but
      also ICLCs regulate myocyte turnover and contribute to both cardiac cellular
      homeostasis and endogenous repair/remodelling after injuries.

PMID- 19382897
TI  - Imaging of language-related brain regions in detoxified alcoholics.
AB  - BACKGROUND: Neuroimaging studies showed clear evidence of alcoholism-related
      damage to the frontal lobes and cerebellum. Although these regions have been
      involved in language processing, language skills are relatively spared in
      alcoholics. Here, we aimed at identifying neural substrates associated with the
      preserved mechanisms of language processing in alcoholics. We hypothesized that
      alcoholics would show a different pattern of neural activity compared with the
      controls. METHODS: Alcoholic and nonalcoholic subjects performed an auditory
      language task while receiving a functional magnetic resonance imaging (fMRI) scan
      in a 1.5 T magnet. This task has been previously shown to solicit the
      comprehension processing in healthy controls, with reliable fMRI response in the
      left frontal and temporal/parietal lobes. RESULTS: Behavioral results showed
      comparable performance (error rates, response time) between the alcoholics and
      the matched controls. However, analysis of the functional data revealed that the
      alcoholics exhibited greater fMRI response in the left middle frontal gyrus (pars
      triangularis), the right superior frontal gyrus, and the cerebellar vermis
      relative to the controls. CONCLUSIONS: These findings suggest that
      frontocerebellar neural activity, supporting the comprehension processing of the
      auditory language task, may require compensatory mechanisms in alcoholics in
      order to maintain the same level of performance as the controls.

PMID- 19382898
TI  - SIAM-Like phenomenon caused by low doses of alcohol.
AB  - BACKGROUND: Swift increase in alcohol metabolism (SIAM) is usually evoked by a
      large dose of ethanol, which is often demonstrated by an abrupt increase in
      oxygen uptake. SIAM was induced by low doses of ethanol and evaluated by
      pharmacokinetic analyses of ethanol and its metabolites. METHODS: Rabbits were
      initially administered 1.0 g/kg of ethanol solution and the same dose was given
      to the bolus group 6 hours after the first injection. The infusion group was
      administered 0.25 g/kg/h of ethanol 2 hours after the first injection. Blood
      concentrations of ethanol, acetaldehyde, and acetate were then determined and
      comparisons were made using pharmacokinetic parameters. RESULTS: A significantly
      higher ethanol elimination rate was observed after re-administration of ethanol
      to the bolus group. Other pharmacokinetic parameters were unaffected. The
      concentration at steady state (Css) for the infusion group was stable. A
      significantly higher level of mean residence time (MRT) in blood acetaldehyde was
      observed for the bolus group, whereas no MRT changes were observed for the
      infusion group. A significantly higher level of blood acetate Css was observed
      after re-administration of ethanol to the bolus group, following the changes in
      area under concentration and MRT. No Css changes were observed for the infusion
      group. The Css of acetate at stage 2 was significantly higher for the bolus
      group, compared to the infusion group. CONCLUSION: Low doses of ethanol enhanced
      alcohol metabolism in rabbits, according to a pharmacokinetic analysis of
      circulating ethanol concentrations. Simultaneous analyses of its metabolites
      followed the kinetic of ethanol.

PMID- 19382896
TI  - PU.1 and partners: regulation of haematopoietic stem cell fate in normal and
      malignant haematopoiesis.
AB  - During normal haematopoiesis, cell development and differentiation programs are
      accomplished by switching 'on' and 'off' specific set of genes. Specificity of
      gene expression is primarily achieved by combinatorial control, i.e. through
      physical and functional interactions among several transcription factors that
      form sequence-specific multiprotein complexes on regulatory regions (gene
      promoters and enhancers). Such combinatorial gene switches permit flexibility of
      regulation and allow numerous developmental decisions to be taken with a limited
      number of regulators. The haematopoietic-specific Ets family transcription factor
      PU.1 regulates many lymphoid- and myeloid-specific gene promoters and enhancers
      by interacting with multiple proteins during haematopoietic development. Such
      protein-protein interactions regulate DNA binding, subcellular localization,
      target gene selection and transcriptional activity of PU.1 itself in response to
      diverse signals including cytokines, growth factors, antigen and cellular
      stresses. Specific domains of PU.1 interact with many protein motifs such as
      bHLH, bZipper, zinc fingers and paired domain for regulating its activity. This
      review focuses on important protein-protein interactions of PU.1 that play a
      crucial role in regulation of normal as well as malignant haematopoiesis. Precise
      delineation of PU.1 protein-partner interacting interface may provide an improved
      insight of the molecular mechanisms underlying haematopoietic stem cell fate
      regulation. Its interactions with some proteins could be targeted to modulate the
      aberrant signalling pathways for reversing the malignant phenotype and to control
      the generation of specific haematopoietic progeny for treatment of haematopoietic
      disorders.

PMID- 19382899
TI  - Alcohol-related disorders in Beijing, China: prevalence, socio-demographic
      correlates, and unmet need for treatment.
AB  - BACKGROUND: The study aimed to determine the prevalence of alcohol use, episodic
      heavy drinking, and alcohol dependence and their socio-demographic correlates in
      Beijing, China. methods: A total of 5,926 subjects were randomly selected in
      Beijing and interviewed using the Composite International Diagnostic Interview
      (CIDI 1.0). Data on basic socio-demographic and current major medical conditions
      were also collected. RESULTS: The 12-month prevalence of alcohol use and episodic
      heavy drinking were 32.5 and 13.8%, respectively. The 12-month and lifetime
      prevalence of alcohol dependence were 1.7 and 4.3%, respectively. Age above 24
      years, male sex, being married and employed, low education level (junior high
      school, primary school or illiterate), rural residence, and having comorbid
      psychiatric disorders were all significantly associated with a higher likelihood
      of alcohol-related disorders. Only 2.4% of the subjects with alcohol dependence
      were receiving treatment, and a mere 1.4% had sought treatment from mental health
      professionals. CONCLUSIONS: Nationwide surveys are urgently needed to further
      explore the prevalence of alcohol-related disorders in China.

PMID- 19382900
TI  - Predictive factors for pure steatosis in alcoholic patients.
AB  - BACKGROUND: Bearing in mind the mechanisms involved in nonalcoholic fatty liver
      disease, this study aims to verify whether metabolic syndrome or its various
      individual components are independent predictive factors for steatosis > or =10%
      in alcoholic patients. METHODS: This study included 281 consecutive alcoholic
      patients with abnormal liver tests and either normal liver histology or steatosis
      <10% (n = 119) or steatosis > or =10% (n = 162). Logistic regression analysis was
      used to study the relationship between metabolic syndrome components and various
      risk factors and the presence of steatosis > or =10%. We assessed apolipoprotein
      A1 (ApoA-1) levels, a major protein component of plasma high-density lipoprotein
      (HDL), rather than HDL-cholesterol levels. RESULTS: Plasma ApoA-1 levels (p <
      0.01), body mass index (BMI) (p < 0.01), and waist circumference (p < 0.05) were
      significantly higher in patients with steatosis > or =10% than in patients with
      normal liver histology or steatosis <10%. A higher percentage of patients with
      steatosis > or =10% had high blood pressure (p = 0.003) than patients with normal
      liver histology or steatosis <10%. In the logistic regression, ApoA-1 [odds ratio
      (OR) = 1.57 (1.10-2.22)], BMI [OR = 1.10 (1.01-1.23)], and high blood pressure
      [OR = 1.84 (1.10-3.06)] were positively and independently correlated with the
      presence of steatosis > or =10%. In the multivariate regression high blood
      pressure was independently and positively correlated with steatosis score (r =
      0.55 +/- 0.26; p < 0.05). On the other hand, when the presence of high blood
      pressure was the dependent variable, the presence of steatosis > or =10%
      positively and independently correlated with it [OR = 1.82 (1.05-3.15)].
      CONCLUSION: In alcoholic patients without fibrosis, ApoA-1, BMI, and high blood
      pressure on the next morning after the admission were predictive of steatosis >
      or =10%. High blood pressure was the only metabolic syndrome component associated
      with the presence of alcoholic steatosis >/=10% and was not correlated with other
      metabolic syndrome components. These findings suggest that steatosis mechanisms
      are different in alcoholic and nonalcoholic fatty liver.

PMID- 19382901
TI  - Ethanol promotes thiamine deficiency-induced neuronal death: involvement of
      double-stranded RNA-activated protein kinase.
AB  - BACKGROUND: Heavy alcohol consumption causes cerebellar degeneration, and the
      underlying mechanism is unclear. Chronic alcoholism is usually associated with
      thiamine deficiency (TD) which is known to induce selective neurodegeneration in
      the brain. However, the role of TD in alcohol-induced cerebellar degeneration
      remains to be elucidated. The double-stranded RNA-activated protein kinase (PKR)
      is a potent antiviral protein. Viral infection or binding to dsRNA causes PKR
      autophosphorylation and subsequent phosphorylation of the alpha-subunit of
      eukaryotic translation factor-2alpha, leading to inhibition of translation or
      apoptosis. PKR can also be activated by cellular stresses. METHODS: In this
      study, we used an in vitro model, cultured cerebellar granule neurons (CGNs), to
      investigate the interaction between TD and ethanol and evaluate the contribution
      of their interaction to neuronal loss. TD was induced by treatment with amprolium
      in association with ethanol. Cell viability was determined by 3-(4,5
      dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide assay. PKR
      expression/phosphorylation and subcellular distribution was analyzed with
      immunoblotting and immunocytochemistry. RESULTS: Thiamine deficiency caused death
      of CGNs but ethanol did not. However, TD plus ethanol induced a much greater cell
      loss than TD alone. TD-induced PKR phosphorylation and ethanol exposure
      significantly promoted TD-induced PKR phosphorylation as well as its nuclear
      translocation. A selective PKR inhibitor not only protected CGNs against TD
      toxicity, but also abolished ethanol potentiation of TD-induced loss of CGNs.
      CONCLUSIONS: Ethanol promoted TD-induced PKR activation and neuronal death. PKR
      may be a convergent protein that mediates the interaction between TD and ethanol.

PMID- 19382902
TI  - Altering the relative abundance of GABA A receptor subunits changes GABA- and
      ethanol-responses in Xenopus oocytes.
AB  - BACKGROUND: Variations in GABRA2 and GABRG3, genes encoding the alpha2 and gamma3
      subunits of the pentameric GABA(A) receptor, are associated with the risk of
      developing alcoholism in adults, conduct disorder at younger ages, and with
      differences in electroencephalographic power in the beta frequency range. The
      SNPs associated with alcoholism did not alter the coding of these genes, and
      extensive DNA sequencing of GABRA2 did not find coding changes in the high-risk
      haplotypes. Therefore, we hypothesize that the associations arise from
      differences in gene expression. METHODS: Here we report studies in Xenopus
      oocytes to examine the functional effects of altering the relative abundance of
      these 2 receptor subunits on GABA current and response to ethanol, as a model of
      potential effects of regulatory differences. RESULTS: When human
      alpha2beta2gamma3 subunits are co-expressed, increasing the amount of the alpha2
      subunit mRNA increased GABA current; in contrast, increasing the amount of the
      gamma3 subunit decreased GABA currents. Acute ethanol treatment of oocytes
      injected with a 1:1:1 or 2:2:1 ratio of alpha2:beta2:gamma3 subunit mRNAs
      resulted in significant potentiation of GABA currents, whereas ethanol inhibited
      GABA currents in cells injected with a 6:2:1 ratio. Overnight treatment with
      ethanol significantly reduced GABA currents in a manner dependent on the ratio of
      subunits. CONCLUSIONS: These studies demonstrate that changes in relative
      expression of GABA(A) receptor subunits alter the response of the resulting
      channels to GABA and to ethanol.

PMID- 19382903
TI  - Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal function
      across the estrous cycle.
AB  - BACKGROUND: Rats prenatally exposed to ethanol (E) typically show increased
      hypothalamic-pituitary-adrenal (HPA) responses to stressors in adulthood.
      Importantly, prenatal ethanol may differentially alter stress responsiveness in
      male and female offspring, suggesting a role for the gonadal hormones in
      mediating the effects of ethanol on HPA activity. We investigated the role of
      ethanol-induced changes in hypothalamic-pituitary-gonadal (HPG) activity in the
      differential HPA regulation observed in E compared to control females across the
      estrous cycle. METHODS: Peripheral hormones and changes in central neuropeptide
      mRNA levels were measured across the estrous cycle in adult female offspring from
      E, pair-fed (PF) and ad libitum-fed control (C) dams. RESULTS: Ethanol females
      showed normal estrous cyclicity (vaginal smears) but delayed sexual maturation
      (vaginal opening). Both HPG and HPA activity were differentially altered in E
      (and in some cases, PF) compared to control females as a function of estrous
      cycle stage. In relation to HPG activity, E and PF females had higher basal and
      stress estradiol (E(2)) levels in proestrus compared to other phases of the
      cycle, and decreased GnRH mRNA levels compared to C females in diestrus. Further,
      E females had greater variation in LH than PF and C females across the cycle, and
      in proestrus, only E females showed a significant LH increase following stress.
      In relation to HPA activity, both basal and stress CORT levels and overall ACTH
      levels were greater in E than in C females in proestrus. Furthermore, AVP mRNA
      levels were increased overall in E compared to PF and C females. CONCLUSIONS:
      These data demonstrate ethanol-induced changes in both HPG and HPA activity that
      are estrous phase-specific, and support the possibility that changes in HPA
      activity in E females may reflect differential sensitivity to ovarian steroids. E
      females appear to have an increased HPA sensitivity to E(2), and a possible shift
      toward AVP regulation of HPA activity. That PF were similar to E females on some
      measures suggests that nutritional effects of diet or food restriction played a
      role in mediating at least some of the changes observed.

PMID- 19382904
TI  - Glycine receptors contribute to hypnosis induced by ethanol.
AB  - BACKGROUND: Glycine is a major inhibitory neurotransmitter in the adult central
      nervous system (CNS), and its receptors (GlyRs) are well known for their effects
      in the spinal cord and the lower brainstem. Accumulating evidence indicates that
      GlyRs are more widely distributed in the CNS, including many supraspinal regions.
      Previous in vitro studies have demonstrated that ethanol potentiates the function
      of these brain GlyRs, yet the behavioral role of the brain GlyRs has not been
      well explored. METHODS: Experiments were conducted in rats. The loss of righting
      reflex (LORR) was used as a marker of the hypnotic state. We compared the LORR
      induced by systematic administration of ethanol and of ketamine in the absence
      and presence of the selective glycine receptor antagonist strychnine. Ketamine is
      a general anesthetic that does not affect GlyRs. RESULTS: Systemically
      administered (by intraperitoneal injection) ethanol and ketamine dose-dependently
      induced LORR in rats. Furthermore, systemically administered (by subcutaneous
      injection) strychnine dose-dependently reduced the percentage of rats exhibiting
      LORR induced by ethanol, increased the onset time, and decreased the duration of
      LORR. Strychnine had no effect, however, on the LORR induced by ketamine.
      CONCLUSIONS: Given that hypnosis is caused by neuronal depression in upper brain
      areas, we therefore conclude that brain GlyRs contribute at least in part to the
      hypnosis induced by ethanol.

PMID- 19382905
TI  - Expression pattern, ethanol-metabolizing activities, and cellular localization of
      alcohol and aldehyde dehydrogenases in human pancreas: implications for
      pathogenesis of alcohol-induced pancreatic injury.
AB  - BACKGROUND: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are
      major enzymes responsible for metabolism of ethanol. Genetic polymorphisms of
      ADH1B, ADH1C, and ALDH2 occur among racial populations. The metabolic effect and
      metabolites contribute to pathogenesis of pancreatic injury. The goal of this
      study was to determine the functional expressions and cellular localization of
      ADH and ALDH families in human pancreas. METHODS: Fifty five surgical specimens
      of normal pancreas as well as 15 samples each for chronic pancreatitis and
      pancreatic cancer from archival formalin-fixed paraffin-embedded tissue specimens
      were investigated. Class-specific antibodies were prepared by affinity
      chromatographies from rabbit antisera raised against recombinant human ADH1C1,
      ADH4, ADH5, ADH7, ALDH1A1, ALDH2, and ALDH3A1. The isozyme expression patterns of
      ADH/ALDH were identified by isoelectric focusing, and the activities were assayed
      spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined
      by immunoblotting, and the cellular localizations were detected by
      immunohistochemistry and histochemistry. RESULTS: At 33 mM ethanol, pH 7.5, the
      activities were significantly different between allelic phenotypes of ADH1B. The
      activity of ALDH2-inactive phenotypes was slightly lower than ALDH2-active
      phenotypes at 200 microM acetaldehyde. The protein contents were in the following
      decreasing order: ALDH1A1, ALDH2, ADH1, and ADH5. ADH1B was detected in the
      acinar cells and ADH1C in the ductular, islet, and stellate cells. The expression
      of ADH1C appeared to be increased in the activated pancreatic stellate cells in
      chronic pancreatitis and pancreatic cancer. CONCLUSIONS: Alcohol dehydrogenase
      and ALDH family members are differentially expressed in the various cell types of
      pancreas. ADH1C may play an important role in modulation of activation of
      pancreatic stellate cells.

PMID- 19382906
TI  - H2O2-induced Ca2+ influx and its inhibition by N-(p-amylcinnamoyl) anthranilic
      acid in the beta-cells: involvement of TRPM2 channels.
AB  - Type 2 melastatin-related transient receptor potential channel (TRPM2), a member
      of the melastatin-related TRP (transient receptor potential) subfamily is a
      Ca(2+)-permeable channel activated by hydrogen peroxide (H(2)O(2)). We have
      investigated the role of TRPM2 channels in mediating the H(2)O(2)-induced
      increase in the cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) in insulin
      secreting cells. In fura-2 loaded INS-1E cells, a widely used model of beta
      cells, and in human beta-cells, H(2)O(2) increased [Ca(2+)](i), in the presence
      of 3 mM glucose, by inducing Ca(2+) influx across the plasma membrane. H(2)O(2)
      induced Ca(2+) influx was not blocked by nimodipine, a blocker of the L-type
      voltage-gated Ca(2+) channels nor by 2-aminoethoxydiphenyl borate, a blocker of
      several TRP channels and store-operated channels, but it was completely blocked
      by N-(p-amylcinnamoyl)anthranilic acid (ACA), a potent inhibitor of TRPM2.
      Adenosine diphosphate phosphate ribose, a specific activator of TRPM2 channel and
      H(2)O(2), induced inward cation currents that were blocked by ACA. Western blot
      using antibodies directed to the epitopes on the N-terminal and on the C-terminal
      parts of TRPM2 identified the full length TRPM2 (TRPM2-L), and the C-terminally
      truncated TRPM2 (TRPM2-S) in human islets. We conclude that functional TRPM2
      channels mediate H(2)O(2)-induced Ca(2+) entry in beta-cells, a process potently
      inhibited by ACA.

PMID- 19382907
TI  - Epicardium: interstitial Cajal-like cells (ICLC) highlighted by
      immunofluorescence.
AB  - During the last few years, there is an increasing interest in the role of the
      epicardium in cardiac development, myocardial remodelling or repair and
      regeneration. Several types of cells were described in the subepicardial loose
      connective tissue, beneath the epicardial mesothe-lium. We showed previously
      (repeatedly) the existence of interstitial Cajal-like cells (ICLCs) in human and
      mammalian myocardium, either in atria or in ventricles. Here, we describe ICLCs
      in adult mice epicardium and primary culture as well as in situ using frozen
      sections. The identification of ICLCs was based on phase contrast microscopy and
      immunophenotyping. We found cells with characteristic morphologic aspects:
      spindle-shaped, triangular or polygonal cell body and typical very long (tens to
      hundreds micrometres) and very thin cyto-plasmic processes, with a distinctive
      'beads-on-a-string' appearance. The dilations contain mitochondria, as
      demonstrated by MitoTracker Green FM labelling of living cells. Epicardial ICLCs
      were found positive for c-kit/CD117 and/or CD34. However, we also observed ICLCs
      positive for c-kit and vimentin. In conclusion, ICLCs represent a distinct cell
      type in the subendocardium, presumably comprising at least two subpopulations:
      (i) c-kit/CD34-positive and (ii) only c-kit-positive. ICLCs might be essential as
      progenitor (or promoter) cells for developing cardiomyocyte lineages in normal
      and/or injured heart.

PMID- 19382908
TI  - Presenilin-2 dampens intracellular Ca2+ stores by increasing Ca2+ leakage and
      reducing Ca2+ uptake.
AB  - We have previously shown that familial Alzheimer's disease mutants of presenilin
      2 (PS2) and, to a lesser extent, of presenilin-1 (PS1) lower the Ca(2+)
      concentration of intracellular stores. We here examined the mechanism by which
      wild-type and mutant PS2 affect store Ca(2+) handling. By using HeLa, SH-SY5Y and
      MEFs as model cells, and recombinant aequorins as Ca(2+) probes, we show evidence
      that transient expression of either wild-type or mutant PS2 increases the passive
      Ca(2+) leakage: both ryanodine- and IP(3)-receptors contribute to Ca(2+) exit out
      of the ER, whereas the ribosome translocon complex is not involved. In SH-SY5Y
      cells and MEFs, wild-type and mutant PS2 potently reduce the uptake of Ca(2+)
      inside the stores, an effect that can be counteracted by over-expression of SERCA
      2B. On this line, in wild-type MEFs, lowering the endogenous level of PS2 by RNA
      interference, increases the Ca(2+)-loading capability of intracellular stores.
      Furthermore, we show that in PS double knockout MEFs, reduction of Ca(2+) stores
      is mimicked by the expression of PS2-D366A, a loss-of-function mutant, uncleaved
      because also devoid of presenilinase activity but not by co-expression of the two
      catalytic active fragments of PS2. In summary, both physiological and increased
      levels of wild-type and mutant PS2 reduce the Ca(2+) uptake by intracellular
      stores. To exert this newly described function, PS2 needs to be in its full
      length form, even if it can subsequently be cleaved.

PMID- 19382909
TI  - Endocytosis via caveolae: alternative pathway with distinct cellular compartments
      to avoid lysosomal degradation?
AB  - Endocytosis--the uptake of extracellular ligands, soluble molecules, protein and
      lipids from the extracellular surface--is a vital process, comprising multiple
      mechanisms, including phagocytosis, macropinocytosis, clathrin-dependent and
      clathrin-independent uptake such as caveolae-mediated and non-caveolar raft
      dependent endocytosis. The best-studied endocytotic pathway for internalizing
      both bulk membrane and specific proteins is the clathrin-mediated endocytosis.
      Although many papers were published about the caveolar endocytosis, it is still
      not known whether it represents an alternative pathway with distinct cellular
      compartments to avoid lysosomal degradation or ligands taken up by caveolae can
      also be targeted to late endosomes/lysosomes. In this paper, we summarize data
      available about caveolar endocytosis. We are especially focussing on the
      intracellular route of caveolae and providing data supporting that caveolar
      endocytosis can join to the classical endocytotic pathway.

PMID- 19382911
TI  - Prolactin regulatory element-binding protein involved in cAMP-mediated
      suppression of adiponectin gene.
AB  - Adiponectin (ApN) has several protective effects against diabetes and
      atherosclerosis. However, the detailed mechanisms of the regulation of the ApN
      gene have not yet been clarified. Prolactin regulatory element-binding (PREB)
      protein has been identified as a factor that regulates insulin gene expression in
      the pancreas. PREB is located not only in the pancreas but also in adipose
      tissue; however, its role in adipose tissue is not known. To analyse the effects
      of PREB on ApN gene transcription, we employed a reporter gene assay and
      electrophoretic mobility shift assay (EMSA). In the cells expressing or knocking
      down the PREB, ApN expression was determined. PREB was located mainly in the
      nuclei of adipose tissue and its cell line, 3T3-L1 cells. The nuclear extract
      contained ApN promoter-binding activity that was super-shifted by PREB antiserum
      in EMSA studies. In the 3T3-L1 cells, the co-expression of PREB and the ApN
      promoter inhibited the activity of the latter. The addition of cAMP to the cells
      increased PREB expression in a dose-dependent manner. A deletional analysis of
      the ApN promoter showed that the PREB-responsive cis-element in the ApN promoter
      mediated the transcriptional effect of PREB, whereas a mutant of this motif in
      the ApN promoter abrogated the effect of PREB, as well as that of cAMP.
      Furthermore, cells expressing or knocking down PREB exhibited decreased and
      increased ApN expression, respectively. These results demonstrate that PREB may
      contribute to the regulation of ApN gene transcription, in response to cAMP
      activation in adipocytes.

PMID- 19382910
TI  - Vitamin D3 signalling in the brain enhances the function of phosphoprotein
      enriched in astrocytes--15 kD (PEA-15).
AB  - In spite of growing evidence linking vitamin D(3) levels to mental health
      disorders, little is known about its direct targets in the brain. This study set
      out to investigate targets of vitamin D(3) in a human brain stem cell line. We
      employed arrays with antibodies directed against more than 600 structural and
      signalling proteins, including phospho-variants. Over 180 proteins responded to
      vitamin D(3), such as cyclin-dependent protein-serine kinase 1/2, epidermal
      growth factor receptor-tyrosine kinase, protein kinase A, protein-serine kinase
      Bgamma and protein-serine kinase Calpha. PEA-15 (phosphoprotein enriched in
      astrocytes-15 kD, also known as PED), known to be involved in various anti
      proliferative and anti-apoptotic effects, was strongly up-regulated. In silico
      promoter analysis revealed conserved binding sites for vitamin D(3) receptor,
      suggesting a strong vitamin D(3) dependency of the PEA-15 promoter. PEA-15 up
      regulation by vitamin D(3) could be confirmed by Western blot in two different
      cell lines. Analysis of mRNA and protein phosphorylation status of PEA-15
      suggests that increased PEA-15 promoter activity and increased protein
      stabilization contribute to the overall rise of PEA-15 protein. In a functional
      test of this novel pathway, we demonstrated that vitamin D(3) was able to rescue
      cells from TRAIL-induced apoptosis through regulation of the PEA-15 expression
      and function. Summarized, our study presents novel targets of vitamin D(3)
      relevant for apoptosis and cell proliferation, and thus strongly supports a
      function of vitamin D(3) in the brain that impacts on processes highly relevant
      for major neurological disorders.

PMID- 19382912
TI  - Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human
      osteoblasts in vitro.
AB  - Although increased bone marrow fat in age-related bone loss has been associated
      with lower trabecular mass, the underlying mechanism responsible remains unknown.
      We hypothesized that marrow adipocytes exert a lipotoxic effect on osteoblast
      function and survival through the reversible biosynthesis of fatty acids (FA)
      into the bone marrow microenvironment. We have used a two-chamber system to co
      culture normal human osteoblasts (NHOst) with differentiating pre-adipocytes in
      the absence or presence of an inhibitor of FA synthase (cerulenin) and separated
      by an insert that allowed unidirectional trafficking of soluble factors only and
      prevented direct cell-cell contact. Supernatants were assayed for the presence of
      FA using mass spectophotometry. After 3 weeks in co-culture, NHOst showed
      significantly lower levels of differentiation and function based on lower
      mineralization and expression of alkaline phosphatase, osterix, osteocalcin and
      Runx2. In addition, NHOst survival was affected by the presence of adipocytes as
      determined by MTS-formazan and TUNEL assays as well as higher activation of
      caspases 3/7. These toxic effects were inhibited by addition of cerulenin.
      Furthermore, culture of NHOst with either adipocyte-conditioned media alone in
      the absence of adipocytes themselves or with the addition of the most predominant
      FA (stearate or palmitate) produced similar toxic results. Finally, Runx2 nuclear
      binding was affected by addition of either adipocyte conditioned media or FA into
      the osteogenic media. We conclude that the presence of FA within the marrow
      milieu can contribute to the age-related changes in bone mass and can be
      prevented by the inhibition of FA synthase.

PMID- 19382913
TI  - Complex patterns of mitochondrial dynamics in human pancreatic cells revealed by
      fluorescent confocal imaging.
AB  - Mitochondrial morphology and intracellular organization are tightly controlled by
      the processes of mitochondrial fission-fusion. Moreover, mitochondrial movement
      and redistribution provide a local ATP supply at cellular sites of particular
      demands. Here we analysed mitochondrial dynamics in isolated primary human
      pancreatic cells. Using real time confocal microscopy and mitochondria-specific
      fluorescent probes tetramethylrhodamine methyl ester and MitoTracker Green we
      documented complex and novel patterns of spatial and temporal organization of
      mitochondria, mitochondrial morphology and motility. The most commonly observed
      types of mitochondrial dynamics were (i) fast fission and fusion; (ii) small
      oscillating movements of the mitochondrial network; (iii) larger movements,
      including filament extension, retraction, fast (0.1-0.3 mum/sec.) and frequent
      oscillating (back and forth) branching in the mitochondrial network; (iv) as well
      as combinations of these actions and (v) long-distance intracellular
      translocation of single spherical mitochondria or separated mitochondrial
      filaments with velocity up to 0.5 mum/sec. Moreover, we show here for the first
      time, a formation of unusual mitochondrial shapes like rings, loops, and
      astonishingly even knots created from one or more mitochondrial filaments. These
      data demonstrate the presence of extensive heterogeneity in mitochondrial
      morphology and dynamics in living cells under primary culture conditions. In
      summary, this study reports new patterns of morphological changes and dynamic
      motion of mitochondria in human pancreatic cells, suggesting an important role of
      integrations of mitochondria with other intracellular structures and systems.

PMID- 19382922
TI  - Are the Australian poultry industries vulnerable to large outbreaks of highly
      pathogenic avian influenza?
AB  - OBJECTIVE: To describe the structure of the Australian poultry industry and
      discuss the potential for highly pathogenic avian influenza (HPAI) to spread
      between Australian poultry farms. PROCEDURE: High densities of poultry farms,
      frequent contacts between farms by service providers, the supply of live poultry
      markets (LPM) and the presence of free-range duck flocks in affected regions have
      been identified as risk factors for the spread of HPAI between flocks in
      outbreaks causing the death or destruction of over 1 million poultry overseas.
      Data on 1,594 commercial Australian chicken meat, chicken egg, duck and turkey
      farms were collected by a telephone questionnaire of farm managers to assess the
      risk of a HPAI outbreak in Australia. RESULTS AND DISCUSSION: Five regions of
      Australia had farm densities comparable to overseas regions that experienced
      widespread HPAI. Common service providers routinely contacted different classes
      and types of farms over wide geographic areas. However, no responding farms
      supplied LPM and the majority of duck farms did not produce free-range ducks.
      CONCLUSION: Outbreaks of HPAI have the potential to cause serious impacts on the
      Australian poultry industry. The risk posted by LPM and free-range ducks is
      limited, but the movement of genetic stock and common service providers could
      spread infection between companies, industries or geographical regions.
      Biosecurity measures are therefore considered critical to limit the secondary
      spread of infection should an outbreak occur.

PMID- 19382914
TI  - Chromosome 6 encoded RNaseT2 protein is a cell growth regulator.
AB  - We have previously shown by chromosome transfer technique that chromosome 6
      alters the phenotype of a variety of tumour cells and SV40 immortalized cells. We
      present here the phenotypic effects of the ectopic expression of RNaseT2, a
      highly conserved ribonuclease encoded by chromosome 6q27, in SV40 immortalized
      cell lines. We contrast our findings with those reported for ovarian carcinoma
      cell lines and an SV40 immortalized cell line transfected with RNaseT2. Although
      RNaseT2 expression is elevated in normal diploid fibroblasts approaching
      senescence (passage 64), forced expression of the gene in immortalized cells does
      not cause them to senesce. A significant reduction was observed in colony forming
      efficiency, anchorage independence and growth rate of cells transfected with
      RNaseT2. The levels of transcripts involved in Akt signalling pathway, cell cycle
      control and pathways related to cell proliferation decreased 2-10-folds in SV40
      immortalized cells in response to RNaseT2 expression. Interestingly, some
      immortalized cells expressed alternatively spliced transcript variants instead of
      the full-length RNaseT2 transcript. Our results are consistent with the
      conclusion that RNaseT2 is a cell growth regulator and it does not induce
      senescence in SV40 immortalized cell lines.

PMID- 19382915
TI  - Apoptosis pathways and their therapeutic exploitation in pancreatic cancer.
AB  - Resistance to apoptosis (programmed cell death) is a characteristic feature of
      human malignancies including pancreatic cancer, which is one of the leading
      causes of cancer deaths in the western world. Defects in this intrinsic cell
      death program can contribute to the multistep process of tumorigenesis, because
      too little cell death can disturb tissue homeostasis. Further, blockade of
      apoptosis pathways can cause treatment failure, because intact apoptosis
      signalling cascades largely mediate therapy-induced cytotoxicity. The elucidation
      of apoptosis pathways in pancreatic carcinoma over the last decade has resulted
      in the identification of various molecular defects. How apoptosis pathways can be
      exploited for the treatment of pancreatic cancer will be discussed in this
      review.

PMID- 19382924
TI  - Cytopathological and histopathological diagnosis of canine splenic disorders.
AB  - OBJECTIVES: To determine (1) the common types of canine splenic disorders, and
      the breeds affected, that are diagnosed by cytopathological and histopathological
      examination in Sydney, Australia and (2) the accuracy of cytopathological
      examination compared with histopathological examination for the diagnosis of
      canine splenic disorders. DESIGN: 69 cytopathological and 51 histopathological
      diagnoses of canine splenic disorders presented to the Veterinary Pathology
      Diagnostic Services, The University of Sydney during 2006 and 2007 were tabulated
      and analysed; 17 cases examined both cytopathologically and histopathologically
      during 2001-07 were also analysed. RESULTS: The most common cytopathological
      diagnoses were benign disorders of growth, vascular disturbances and necrosis
      (29%), followed by no abnormalities detectable (28%), malignant neoplasms (20%),
      equivocal diagnoses (20%) and inflammatory disorders (3%). The most common breeds
      were Kelpie crosses and mixed breeds. The most common histopathological diagnoses
      were benign disorders of growth, vascular disturbances and necrosis (49%),
      followed by malignant neoplasms (43%) and inflammatory disorders (8%). The most
      common breeds were German Shepherd Dogs, Boxers and Maltese Terriers.
      Cytopathological and histopathological diagnoses were in complete agreement in
      59% of cases, partial agreement in 29% and disagreement in 12%. CONCLUSION:
      Benign disorders of growth, vascular disturbances and necrosis were the most
      commonly diagnosed canine splenic disorders, both cytopathologically and
      histopathologically. Kelpie crosses presented most frequently for
      cytopathological examination. German Shepherd Dogs were the most common breed
      diagnosed histopathologically with haemangiosarcoma. Although cytopathological
      and histopathological splenic examinations are complementary for diagnosis, this
      study has shown a high correlation for complete and partial agreement between the
      two.

PMID- 19382925
TI  - Dermatoses caused by infestations of immature Ixodes spp. on dogs and cats in
      Sydney, Australia.
AB  - Infestations of larval and nymphal Ixodes spp. were identified in 16 dogs and 16
      cats from several small animal clinics in Sydney. Cases occurred in late summer
      or autumn, peaking in February, and were seasonally recurrent in some
      individuals. Clinical signs of infestation included a papular dermatitis and
      irritation or pruritus that ranged from severe to mild or absent. The
      distribution of tick attachment tended to be cranial and ventral, with the face,
      legs, axillae and ventrum the most commonly affected sites. The estimated number
      of ticks in each infestation varied from less than 10 to more than 100. Basic
      morphological examination of ticks collected from affected animals was performed
      by attending veterinarians using light microscopy, and larvae and nymphs
      belonging to the Ixodes genus were identified. Ticks collected from 17 animals
      and submitted to the Department of Medical Entomology, Westmead Hospital were
      putatively identified as I. trichosuri (57%) and I. holocyclus (25%) larvae.
      Histopathological samples of attachment sites collected from three dogs and one
      cat were characterised by ticks attached in well-demarcated invaginations of the
      skin ('tick craters') associated with variable epidermal and/or dermal necrosis,
      focal eosinophilic intraspinous pustules, mild to marked eosinophilic and
      neutrophilic, superficial to deep, dermal perivascular to interstitial
      inflammation, and moderate to marked superficial dermal oedema and red cell
      extravasation. A range of topical acaricidal preparations, including fipronil and
      synthetic pyrethroids, were used for treatment.

PMID- 19382926
TI  - Seizures during medetomindine sedation and local anaesthesia in two dogs
      undergoing skin biopsy.
AB  - Each of two dogs presented for multiple skin biopsies were sedated with
      intravenous medetomidine and lignocaine was injected subcutaneously to provide
      local anaesthesia for skin biopsy. One dog had a seizure during skin biopsy and
      again immediately following reversal of medetomidine with atipamezole. The other
      dog developed seizures 2 h following skin biopsy at which time the medetomidine
      was reversed with atipamezole. Both dogs were neurologically normal with no
      history of seizures prior to the procedure and remained neurologically normal for
      14 weeks and 9 months, respectively, following the procedure. A drug interaction
      between the alpha(2)-adrenergic agonist medetomidine and lignocaine is suspected
      and highlights the potential for seizures following the subcutaneous
      administration of relatively large doses of lignocaine under medetomidine
      sedation.

PMID- 19382928
TI  - Inherited diseases of Australian Holstein-Friesian cattle.
AB  - Inherited disorders are of major importance in Holstein-Friesian cattle, a breed
      that now dominates the global dairy industry. Recent developments in the breed
      reflect intensive selection programs for production traits, identifying elite
      sires whose genotypes are rapidly spread worldwide through the use of breeding
      programs involving advanced reproductive technologies. These elite sires carry
      mutations responsible for disease. Consequently, the mating of descendants of an
      elite sire (as with any sire) substantially increases the risk of producing
      defective progeny. The important inherited disorder citrullinaemia was
      disseminated globally in the 1970s and first reported in Australian Holstein
      Friesians. However, a range of inherited disorders more recently recognised
      internationally in this breed have remained unreported in Australia, although
      recent genotyping studies suggest they have probably occurred. A survey of these
      disorders suggests a decline in surveillance for such diseases in Australia.
      Clinical and pathological descriptions are presented to enable practitioners and
      producers to recognise and report these disorders, and a proposal is advanced to
      establish a health program to manage this issue.

PMID- 19382930
TI  - Double-outlet right ventricle in a 10-month-old Friesian filly.
AB  - A 10-month-old Friesian filly had a presentation that was consistent with chronic
      left- and right-sided congestive heart failure. Clinical pathology findings
      included abnormal haematological and biochemical variables, abnormal blood gas
      values and increased serum concentration of cardiac troponin I. Echocardiography
      revealed cardiac chamber dilation and dextropositioning of the aorta. Radiography
      revealed a generally enlarged heart and pulmonary interstitial infiltration.
      These findings were supported at necropsy and the diagnosis of double-outlet
      right ventricle was confirmed. The pathological changes and physiological
      responses subsequent to double-outlet right ventricle have not previously been
      described in detail in horses. Clinical progression closely resembles that seen
      in humans, in whom antemortem diagnosis relies on echocardiography. In horses,
      complex cardiac disease presents a diagnostic challenge to the clinician.
      Appropriate therapy must be based on an accurate diagnosis.

PMID- 19382929
TI  - Efficacy against Fasciola hepatica and the pharmacokinetics of triclabendazole
      administered by oral and topical routes.
AB  - OBJECTIVE: To determine the efficacy of triclabendazole (TCBZ) against 28-day
      old, early immature liver fluke in cattle and its pharmacokinetics following
      administration by the oral or topical (pour-on) route. PROCEDURES: Cattle (n =
      18) were infected with 500 TCBZ-susceptible liver fluke metacercariae and
      randomly allocated to three groups. At 28 days after infection, the groups were:
      (1) untreated controls; (2) treated with oral TCBZ at 12 mg/kg in combination
      with oxfendazole and selenium (TOS); (3) treated with pour-on TCBZ at 30 mg/kg in
      combination with abamectin (TA). Blood samples were taken immediately prior to
      treatment and serially after treatment to assess the plasma profile of TCBZ
      metabolites. Ten weeks after treatment all animals were slaughtered and total
      liver fluke counts, fluke egg counts and liver pathology were assessed. RESULTS:
      Both the TOS and TA treatments resulted in significant reductions of 28-day-old
      liver fluke, as assessed by fluke counts and fluke egg counts at slaughter, and
      the reductions following TOS treatment were significantly greater than those
      following TA treatment. The blood profile of TCBZ metabolites in TOS-treated
      animals showed a significantly greater area under the plasma concentration time
      curve and a higher maximum observed concentration than those treated with TA.
      There was significantly less liver pathology in TOS-treated animals than in the
      TA-treated animals. CONCLUSION: TCBZ administered orally at 12 mg/kg resulted in
      greater efficacy against 28-day-old, early immature liver fluke than was achieved
      by topical administration at 30 mg/kg. Plasma metabolites of TCBZ were higher and
      liver pathology was less in TOS-treated animals than in TA-treated animals.

PMID- 19382932
TI  - Consumptive emasculation: the ecological and evolutionary consequences of pollen
      theft.
AB  - Many of the diverse animals that consume floral rewards act as efficient
      pollinators; however, others 'steal' rewards without 'paying' for them by
      pollinating. In contrast to the extensive studies of the ecological and
      evolutionary consequences of nectar theft, pollen theft and its implications
      remain largely neglected, even though it affects plant reproduction more
      directly. Here we review existing studies of pollen theft and find that: (1) most
      pollen thieves pollinate other plant species, suggesting that theft generally
      arises from a mismatch between the flower and thief that precludes pollen
      deposition, (2) bees are the most commonly documented pollen thieves, and (3) the
      floral traits that typically facilitate pollen theft involve either spatial or
      temporal separation of sex function within flowers (herkogamy and dichogamy,
      respectively). Given that herkogamy and dichogamy occur commonly and that bees
      are globally the most important floral visitors, pollen theft is likely a greatly
      under-appreciated component of floral ecology and influence on floral evolution.
      We identify the mechanisms by which pollen theft can affect plant fitness, and
      review the evidence for theft-induced ecological effects, including pollen
      limitation. We then explore the consequences of pollen theft for the evolution of
      floral traits and sexual systems, and conclude by identifying key directions for
      future research.

PMID- 19382933
TI  - Extended phenotypes as signals.
AB  - Animal signals may result from construction behaviour and can provide receivers
      with essential information in various contexts. Here we explore the potential
      benefits of extended phenotypes with a signalling function as compared to bodily
      ornaments and behavioural displays. Their independence of the body, their
      physical persistence and the morphological and cognitive conditions required for
      their construction allow unique communication possibilities. We classify various
      levels of information transfer by extended phenotype signals and explore the
      differences between secreted signals and signals resulting from collection and
      construction, which usually involve higher behavioural complexity. We examine
      evolutionary pathways of extended phenotypes with a signalling function with help
      of a comparative evaluation and conclude that often constructions first provide a
      direct fitness benefit, with a signalling function becoming more and more
      prominent during evolutionary progression. The abundance and variability of
      extended phenotypes as signals is impressive and provides unique possibilities
      for animal communication research.

PMID- 19382934
TI  - A comparative view on mechanisms and functions of skeletal remodelling in teleost
      fish, with special emphasis on osteoclasts and their function.
AB  - Resorption and remodelling of skeletal tissues is required for development and
      growth, mechanical adaptation, repair, and mineral homeostasis of the vertebrate
      skeleton. Here we review for the first time the current knowledge about
      resorption and remodelling of the skeleton in teleost fish, the largest and most
      diverse group of extant vertebrates. Teleost species are increasingly used in
      aquaculture and as models in biomedical skeletal research. Thus, detailed
      knowledge is required to establish the differences and similarities between
      mammalian and teleost skeletal remodelling, and between distantly related species
      such as zebrafish (Danio rerio) and medaka (Oryzias latipes). The cellular
      mechanisms of differentiation and activation of osteoclasts and the functions of
      teleost skeletal remodelling are described. Several characteristics, related to
      skeletal remodelling, distinguish teleosts from mammals. These characteristics
      include (a) the absence of osteocytes in most species; (b) the absence of
      haematopoietic bone marrow tissue; (c) the abundance of small mononucleated
      osteoclasts performing non-lacunar (smooth) bone resorption, in addition to or
      instead of multinucleated osteoclasts; and (d) a phosphorus- rather than calcium
      driven mineral homeostasis (mainly affecting the postcranial dermal skeleton).
      Furthermore, (e) skeletal resorption is often absent from particular sites, due
      to sparse or lacking endochondral ossification. Based on the mode of skeletal
      remodelling in early ontogeny of all teleosts and in later stages of development
      of teleosts with acellular bone we suggest a link between acellular bone and the
      predominance of mononucleated osteoclasts, on the one hand, and cellular bone and
      multinucleated osteoclasts on the other. The evolutionary origin of skeletal
      remodelling is discussed and whether mononucleated osteoclasts represent an
      ancestral type of resorbing cells. Revealing the differentiation and activation
      of teleost skeletal resorbing cells, in the absence of several factors that
      trigger mammalian osteoclast differentiation, is a current challenge.
      Understanding which characters of teleost bone remodelling are derived and which
      characters are conserved should enhance our understanding of the process in fish
      and may provide insights into alternative pathways of bone remodelling in
      mammals.

PMID- 19382936
TI  - Resources and transgenesis techniques for functional genomics in Xenopus.
AB  - Recent developments in genomic resources and high-throughput transgenesis
      techniques have allowed Xenopus to 'metamorphose' from a classic model for
      embryology to a leading-edge experimental system for functional genomics. This
      process has incorporated the fast-breeding diploid frog, Xenopus tropicalis, as a
      new model-system for vertebrate genomics and genetics. Sequencing of the X.
      tropicalis genome is nearly complete, and its comparison with mammalian sequences
      offers a reliable guide for the genome-wide prediction of cis-regulatory
      elements. Unique cDNA sets have been generated for both X. tropicalis and X.
      laevis, which have facilitated non-redundant, systematic gene expression
      screening and comprehensive gene expression analysis. A variety of transgenesis
      techniques are available for both X. laevis and X. tropicalis, and the
      appropriate procedure may be chosen depending on the purpose for which it is
      required. Effective use of these resources and techniques will help to reveal the
      overall picture of the complex wiring of gene regulatory networks that control
      vertebrate development.

PMID- 19382937
TI  - Molecular features of thyroid hormone-regulated skin remodeling in Xenopus laevis
      during metamorphosis.
AB  - Amphibian body skin provides an opportunity to investigate the molecular
      mechanism of thyroid hormone (TH)-dependent organ remodeling during
      metamorphosis. Global gene expression changes in the TH-dependent body skin
      remodeling were studied with microarray analysis. We identified 401 genes that
      were differentially expressed more than fourfold for 7 days after TH-treatment.
      As expected, larval- and adult-type keratin genes were significantly inactivated
      and activated, respectively. The expression changes of the Gene Ontology
      annotated genes demonstrated significant correlation with the morphological and
      physiological changes in body skin metamorphosis. The 'transcription and
      proteolysis' category genes were first upregulated 1 day after TH-treatment.
      Subsequently, the 'cell cycle' category genes were activated at 3 days. The
      'defense response' and 'immune response' category genes were the late TH-response
      genes, which were downregulated and upregulated at 5 and 7 days, respectively.
      From these genes, adult-type keratin-c (xak-c) gene was selected as a suitable
      gene to visually monitor the emergence of adult-type epidermal cells during skin
      remodeling, because the gene is specifically expressed in adult epidermal basal
      cells. We generated enhanced green fluorescent protein (EGFP)-transgenic Xenopus
      laevis driven by the promoter of xak-c gene. The keratin promoter faithfully
      expressed the EGFP gene in adult-type basal cells. Spatial and temporal EGFP
      fluorescence patterns of filial 1 (F1)-offspring tadpoles visually demonstrated
      an event of sequential replacement of larval keratinocytes with the newly
      generated adult counterparts.

PMID- 19382938
TI  - Inhibition of stored Ca2+ release disrupts convergence-related cell movements in
      the lateral intermediate mesoderm resulting in abnormal positioning and
      morphology of the pronephric anlagen in intact zebrafish embryos.
AB  - Ca(2+) is a highly versatile intra- and intercellular signal that has been
      reported to regulate a variety of different pattern-forming processes during
      early development. To investigate the potential role of Ca(2+) signaling in
      regulating convergence-related cell movements, and the positioning and morphology
      of the pronephric anlagen, we treated zebrafish embryos from 11.5 h
      postfertilization (hpf; i.e. just before the pronephric anlagen are
      morphologically distinguishable in the lateral intermediate mesoderm; LIM) to 16
      hpf, with a variety of membrane permeable pharmacological reagents known to
      modulate [Ca(2+)](i). The effect of these treatments on pronephric anlagen
      positioning and morphology was determined in both fixed and live embryos via in
      situ hybridization using the pronephic-specific probes, cdh17, pax2.1 and sim1,
      and confocal imaging of BODIPY FL C(5)-ceramide-labeled embryos, respectively. We
      report that Ca(2+) released from intracellular stores via inositol 1,4,5
      trisphosphate receptors plays a significant role in the positioning and
      morphology of the pronephric anlagen, but does not affect the fate determination
      of the LIM cells that form these primordia. Our data suggest that when Ca(2+)
      release is inhibited, the resulting effects on the pronephric anlagen are a
      consequence of the disruption of normal convergence-related movements of LIM
      cells toward the embryonic midline.

PMID- 19382939
TI  - Developmental expression of Xenopus myosin 1d and identification of a myo1d tail
      homology that overlaps TH1.
AB  - Xenopus laevis myosin 1d (XlMyo1d) is a member of the myosin I class, subclass 4.
      Members of this class are single headed, bind calmodulin light chains and have
      lipid binding domains in their tails. The rat myo1d homologue has been implicated
      in endosome vesicle recycling in epithelial cells. Mutations in the Drosophila
      myosin 1d homologue cause situs inversus in the abdomen. The XlMyo1d cDNA has
      been cloned and the derived amino acid sequence is 80% identical to the rat and
      human homologues. Sequence comparison revealed a novel isoform-specific tail
      homology embedded in the Tail Homology 1 (TH1) domain characteristic of myosin I
      isoforms. Western blot analysis using a polyclonal antibody raised against an
      isoform-specific peptide showed that the protein is present in eggs and levels
      increase at early neurula through tadpole stages. Whole mount in situ
      hybridization using a probe containing the 5'UTR (untranslated region) showed
      that XlMyo1d mRNA is expressed in neural tube, pre-somitic mesoderm, somites and
      all three segments of cranial neural crest cells during their migration. Sections
      of the in situ hybridizations revealed that during somitogenesis, XlMyo1d mRNA
      was localized to a stripe overlapping the nuclear region of somites during early
      tadpole stages.

PMID- 19382940
TI  - Expression of the apoptosis inducer gene head involution defective in primordial
      germ cells of the Drosophila embryo requires eiger, p53, and loki function.
AB  - Nanos (Nos) is an evolutionarily conserved protein essential for the maintenance
      of primordial germ cells (PGCs). In Drosophila, the PGCs or pole cells express
      head involution defective (hid), which is required for caspase activation, but
      its translation is repressed by maternal Nos. In the absence of Nos activity,
      translation of hid mRNA into protein induces apoptosis in pole cells. However, it
      remains unclear how hid mRNA is regulated in pole cells. Here, we report that hid
      expression requires eiger (egr), a tumor necrosis factor ligand (TNF) homologue,
      which is induced in pole cells by decapentaplegic (dpp). In addition, we
      demonstrate that p53 and loki (lok), a damage-activated kinase known to be
      required for p53 phosphorylation, are both required for hid expression in pole
      cells. Since maternal lok mRNA is enriched in pole cells, it is possible that
      ubiquitously distributed p53 is activated in pole cells by maternal Lok. We
      propose that hid expression is activated in a pole cell-specific manner by
      loki/p53 and dpp/egr during embryogenesis.

PMID- 19382941
TI  - Analysis of gene expressions of embryonic stem-derived Pdx1-expressing cells:
      implications of genes involved in pancreas differentiation.
AB  - We have recently reported the method by which embryonic stem (ES) cells were
      induced into Pdx1-expressing cells. To gain insights into the ES cell-derived
      Pdx1-expressing cells, we examined gene expression profiles of the cells by
      microarray experiments. Microarray analyses followed by a comparison with the
      data of the cells in developing pancreatic and adult islet suggested that the ES
      cell-derived Pdx1-positive cells were immature pancreatic progenitor cells with
      endodermal characteristics. The analyses of the genes upregulated in the ES cell
      derived Pdx1-positive cells would give us knowledge on early pancreatic
      development. Here, we first listed the genes and found that these contained not
      only those known to be expressed in the endoderm or pancreatic progenitor cells,
      but also those known to be involved in left-right axis formation. Second, we
      examined the gene expression patterns and found that several genes were expressed
      in the ventral foregut lip at the anterior intestinal portal in E8.5 embryo.
      Given that the Pdx1/GFP-expressing cells are first observed in the same region at
      the anterior intestinal portal, these results suggest that the pancreatic
      progenitor cells first give rise at the ventral endoderm prior to the formation
      of dorsal and ventral pancreatic buds.

PMID- 19382943
TI  - Subtle systolic dysfunction may be associated with the tendency to develop
      diastolic heart failure in patients with preserved left ventricular ejection
      fraction.
AB  - BACKGROUND: We looked for an answer to the question of whether diastolic heart
      failure (DHF) is a reality or all heart failures are systolic. METHOD: 300 cases
      (hypertensive, aged, obese, etc.), not being diagnosed DHF, with preserved left
      ventricular (LV) ejection fraction (EF) but having the tendency to develop DHF in
      future were examined. One hundred and eighty cases without exclusion criteria
      were selected. Cases were assigned to three groups according to noninvasively
      obtained pulmonary capillary wedge pressure (PCWP). RESULTS: In cases with higher
      PCWP (>10 mmHg), transmitral A velocity was increased (P < 0.001) and among the
      pulsed wave tissue Doppler imaging (pw-TDI) parameters Ea velocity was decreased
      (P < 0.001) and Ea-dt was prolonged (P < 0.005). In cases with lower PCWP (<8
      mmHg), transmitral E velocity was higher (P< 0.001). Furthermore, a more
      meaningful relationship was found between PCWP and systolic pw-TDI parameters. In
      all the groups, it was observed that Sa velocity was progressively decreased and
      Q-Sa interval was progressively prolonged as PCWP increased (for all the groups P
      < 0.046). CONCLUSION: The question whether DHF is a reality or all heart failures
      are systolic may be answered as follows. Subtle systolic dysfunction may be
      associated with the tendency to develop DHF in patients with preserved LV
      ejection fraction. As in systolic heart failure (EF < 45%), in patients with
      preserved systolic function (EF > or = 45%), systolic and diastolic functions may
      impair together. The pw-TDI method may be more sensitive than standard
      echocardiography parameters in detection of systolic dysfunction in cases with
      preserved EF.

PMID- 19382944
TI  - Reduction in mitral regurgitation in patients undergoing cardiac
      resynchronization treatment: assessment of predictors by two-dimensional radial
      strain echocardiography.
AB  - BACKGROUND: We utilized the novel approach of 2D radial strain (2-DRS) to
      evaluate whether left ventricular (LV) mechanical dyssynchrony in mid-LV segments
      corresponding to papillary muscles insertion sites can predict early mitral
      regurgitation (MR) reduction post-cardiac resynchronization therapy (CRT).
      METHODS: We evaluated 32 patients undergoing CRT (mean age 64 +/- 17 years, 54%
      males) with MR grade > or =3 determined by the MR jet area/left atrial area ratio
      (JA/LAA). RESULTS: Fifteen (47%) patients responded to CRT (JA/LAA) < 25%). Sixty
      seven percent of responders had mild or no residual MR and 33% had mild-to
      moderate MR, while 70% of nonresponders had grade 3 or 4 MR (P = 0.0001) post
      CRT. The percent reduction in LV end-systolic volume was significantly higher in
      responders (P = 0.03), as was improvement in LVEF (P = 0.007). Significant delay
      of time-to-peak 2-DRS in the midposterior and inferior segments prior to CRT was
      found in responders compared with nonresponders (580 +/- 58 vs. 486 +/- 94, P =
      0.002 and 596 +/- 79 vs. 478 +/- 127 ms, P = 0.005, respectively). Responders
      also had higher peak positive systolic 2-DRS in the posterior and inferior
      segments compared to nonresponders (22 +/- 13 vs. 12 +/- 7%, P = 0.01 and 17 +/-
      9 vs. 9 +/- 7%, P = 0.02, respectively). Logistic regression analysis showed that
      the differences in pre-CRT inferoanterior time-to-peak 2-DRS of >110 ms and
      MRJA/LAA <40% as well as 2-DRS >18% in the posterior wall were significant
      predictors of post-CRT improvement in MR. CONCLUSION: The presence of a
      significant time-to-peak delay on 2-DRS between inferior and anterior LV
      segments, preserved strain of posterior wall, and MRJA/LAA <40% were found to be
      associated with significant MR reduction in patients post-CRT.

PMID- 19382945
TI  - Immediate change in pulmonary venous flow pattern after deployment of occluder
      device for atrial septal defect.
AB  - Transcatheter closure of a secundum defect using a septal occluder is a safe and
      effective procedure based on long-term follow-up, but no clinical studies have
      examined immediate hemodynamic changes. We evaluated pulmonary venous flow
      velocity pattern before and immediately after deployment of the Amplatzer septal
      occluder for closure of atrial septal defect. From May 2003 to January 2005, 48
      patients with secundum atrial septal defect received transcatheter closure with
      complete occlusion. Patients were divided into two groups according to age:
      pediatric group, under 16 years (n = 30, age 7.3 +/- 3.2 years), and adult group,
      16 years or older (n = 18, age 30.1 +/- 11.4 years). Pulmonary venous flow
      pattern was recorded by transesophageal echocardiography before and immediately
      after occluder deployment. Immediately after deployment in both patient groups,
      pulmonary vein systolic (S) and diastolic (D) wave velocity decreased, but atrial
      reversal (AR) wave velocity increased. In the pediatric group, S-wave was 56.1 +/
      17.1 versus 35.5 +/- 11.3 cm/sec (P < 0.001); D-wave was 57.6 +/- 12.5 versus
      42.9 +/- 11.8 cm/sec (P < 0.001); and AR wave velocity was 12.2 +/- 3.8 versus
      15.5 +/- 4.1 cm/sec (P < 0.001). In the adult group, S-wave was 48.4 +/- 13.7
      versus 32.7 +/- 10.3 cm/sec (P < 0.001); D-wave was 51.9 +/- 11.7 versus 38.0 +/-
      8.5 m/sec (P < 0.001); and AR wave velocity was 12.1 +/- 4.1 versus 16.2 +/- 4.9
      cm/sec (P < 0.001). Comparison of pulmonary venous flow before and immediately
      after deployment of the Amplatzer septal occluder provides an excellent model to
      evaluate the influence of an atrial communication on pulmonary venous flow.
      Pulmonary venous forward flow decreases following atrial septal defect (ASD)
      closure.

PMID- 19382946
TI  - Continuing medical education program in Echocardiography.

PMID- 19382947
TI  - Live/real time three-dimensional transthoracic echocardiographic assessment of
      bicuspid aortic valve morphology.
AB  - We describe the usefulness of three-dimensional transthoracic echocardiography
      (3D TTE) in the assessment of bicuspid aortic valve morphology in an adult
      patient with no stenosis but severe aortic regurgitation.

PMID- 19382948
TI  - Three-dimensional imaging of a comma-shaped right ventricular hydatid cyst.
AB  - We report herein a hydatid cyst of the right ventricle and its two- and three
      dimensional echocardiographic appearance.

PMID- 19382949
TI  - Buckling of the transesophageal echocardiography probe.

PMID- 19382950
TI  - Regarding article, "A new parameter of pulsed-wave tissue Doppler imaging: IVRa".

PMID- 19382953
TI  - Molecular and behavioral analysis of the intron 2 repeat polymorphism in the
      canine dopamine D4 receptor gene.
AB  - Genetic polymorphisms in the human dopamine D4 receptor (DRD4) gene, especially
      the exon 3 variable number of tandem repeats (VNTR), have been related to several
      psychiatric disorders and personality traits. A homologous exon 3 VNTR has been
      described in dogs, and we previously showed an association between the DRD4 exon
      3 polymorphism and activity/impulsivity trait in German shepherds. In this study,
      we present a detailed analysis of the intron 2 VNTR of the DRD4 gene. A short and
      a long form of the intronic variation were identified in 678 unrelated dogs from
      five breeds and in 22 wolves. For molecular analysis, the intron 2 region was
      cloned into a promoterless luciferase reporter vector that led to an elevation in
      transcriptional activity. Moreover, an allelic difference in promoter activity
      was detected, and a repressive effect of the long allele was observed. Behavioral
      analysis of 96 unrelated German shepherds showed a significant association
      between the social impulsivity endophenotype of the Greeting Test and both the
      exonic (P = 0.002) and the intronic (P = 0.003) VNTRs of the DRD4 gene. Moreover,
      an additive effect of the two polymorphisms was also shown (Spearman's rho =
      0.356, P = 0.0004). In conclusion, these results give further support to our
      previous findings that the DRD4 gene is associated with dog behavior. We also
      present molecular evidence for the functional role of the intron 2 VNTR in the
      canine DRD4 gene.

PMID- 19382954
TI  - The influence of chemical interactions at the human surface on breathing zone
      levels of reactants and products.
AB  - Using computational fluid dynamics simulations of an occupant in a ventilated
      room, we find that breathing zone ozone levels can be substantially lower and
      ozone reaction products associated with human surfaces (ORPHS) levels
      considerably higher than room levels. For air exchange rates <3/h, the ratio of
      the breathing zone to the ozone concentration 1 m from the body (bulk air),
      r(ozone), ranges from 0.59 to 0.75 for floor or ceiling air supply. ORPHS are
      enriched in the breathing zone, with concentrations for these conditions ranging
      from 1.2 to 2.5 greater than bulk air concentrations. At high air exchange rates
      (>8/h), the breathing zone concentrations approach bulk air concentrations
      (r(ozone) > 0.9) with a floor supply, whereas large concentration gradients occur
      between breathing zone and bulk air with a ceiling supply. At these high air
      exchange rates, ORPHS levels are 1.6-2.0 and 2.9-6.0 times the bulk air
      concentrations for floor and ceiling supply, respectively. The extent of
      depletion of ozone or enrichment of ORPHS is large enough that reliance on micro
      environmental measurements alone, to assess the intake of ozone or ORPHS, is
      undesirable. PRACTICAL IMPLICATIONS: Chemical reactions between ozone and human
      and clothing surfaces are predicted to significantly reduce ozone concentrations,
      and increase ozone reaction products associated with human surfaces (ORPHS)
      concentrations, in the breathing zone, relative to those concentrations in the
      larger microenvironment of a room. Existing measurements may overestimate ozone
      exposure and intake in typical indoor environments.

PMID- 19382955
TI  - Assessment and predictor determination of indoor aldehyde levels in Paris newborn
      babies' homes.
AB  - Exposure to indoor chemical air pollutants expected to be potentially involved in
      allergic respiratory diseases in infants is poorly documented. A specific
      environmental investigation included in a birth cohort study was carried out to
      first assess indoor airborne aldehyde levels, using passive devices and their
      variability within 1 year (1, 6, 9 and 12 months) in the bedroom of 196 Paris
      infants, and second, to identify predictors for aldehyde concentrations using
      interviewer administered questionnaires about housing factors. Comfort parameters
      and carbon dioxide levels were measured simultaneously. Aldehydes were detected
      in almost all dwellings and geometric mean levels (geometric standard deviation)
      at the first visit were respectively for formaldehyde, acetaldehyde, hexanal, and
      pentanal 19.4 (1.7) microg/m(3), 8.9 (1.8) microg/m(3), 25.3 (3.1) microg/m(3),
      3.7 (2.3) microg/m(3), consistent with earlier published results. Generalized
      Estimating Equation multivariate analyses showed that, apart from comfort
      parameters, aeration and season, the main indoor aldehyde sources were either
      continuous (building materials and coverings especially when they were new) or
      discontinuous (smoking, use of air fresheners and cleaning products, DIY etc...).
      Finally, the data collected by questionnaires should be sufficient to enable us
      to classify each infant in our cohort study according to his/her degree of
      exposure to the main aldehydes. PRACTICAL IMPLICATIONS: This analysis contributed
      to document indoor aldehyde levels in Parisian homes and to identify factors
      determining these levels. In the major part of newborn babies' homes, indoor
      formaldehyde levels were above the guideline value of 10 microg/m(3) proposed by
      the French Agency for Environmental and Occupational Health Safety for long-term
      exposure. Given this result, it is essential to study the health impact of
      exposure to aldehydes especially formaldehyde on the incidence of respiratory and
      allergic symptoms, particularly during the first months of life.

PMID- 19382957
TI  - Transformations in dreaming and characters in the psychoanalytic field.
AB  - Having reviewed certain similarities and differences between the various
      psychoanalytic models (historical reconstruction/development of the container and
      of the mind's metabolic and transformational function; the significance to be
      attributed to dream-type material; reality gradients of narrations; tolerability
      of truth/lies as polar opposites; and the form in which characters are understood
      in a psychoanalytic session), the author uses clinical material to demonstrate
      his conception of a session as a virtual reality in which the central operation
      is transformation in dreaming (de-construction, de-concretization, and re
      dreaming), accompanied in particular by the development of this attitude in both
      patient and analyst as an antidote to the operations of transformation in
      hallucinosis that bear witness to the failure of the functions of meaning
      generation. The theoretical roots of this model are traced in the concept of the
      field and its developments as a constantly expanding oneiric holographic field;
      in the developments of Bion's ideas (waking dream thought and its derivatives,
      and the patient as signaller of the movements of the field); and in the
      contributions of narratology (narrative transformations and the transformations
      of characters and screenplays). Stress is also laid on the transition from a
      psychoanalysis directed predominantly towards contents to a psychoanalysis that
      emphasizes the development of the instruments for dreaming, feeling, and
      thinking. An extensive case history and a session reported in its entirety are
      presented so as to convey a living impression of the ongoing process, in the
      consulting room, of the unsaturated co-construction of an emotional reality in
      the throes of continuous transformation. The author also describes the technical
      implications of this model in terms of forms of interpretation, the
      countertransference, reveries, and, in particular, how the analyst listens to the
      patient's communications. The paper ends with an exploration of the concepts of
      grasping (in the sense of clinging to the known) and casting (in relation to what
      is as yet undefined but seeking representation and transformation) as a further
      oscillation of the minds of the analyst and the patient in addition to those
      familiar from classical psychoanalysis.

PMID- 19382958
TI  - Grasping psychoanalysts' practice in its own merits.
AB  - The central objective of this presentation is to reflect on the obstacles
      involved in the task proposed by the Chicago Congress, which is to explore
      convergences and divergences in psychoanalytic practice. The author discusses two
      major obstacles. First, the epistemological and methodological problems in
      relation to the construction of theory in psychoanalysis and especially the
      inaccessibility, in any reliable way, of what psychoanalysts really do in the
      intimacy of their practice. He proposes to separate, at least in part, theory
      from practice in psychoanalysis, in an attempt to grasp psychoanalysts' practice
      in its own merits. He then outlines a phenomenology of the practice of
      psychoanalysis, which reveals that, in their work with patients, analysts are
      guided more by practical reasons than theoretical reasons; that is, their
      interventions are predictions rather than explanations. Since these practical
      reasons need to be validated constantly in the analytic relationship based on
      their effects, he discusses the subject of validation in the clinical context of
      the core theory of therapeutic change in psychoanalysis, that is, the conditions
      required for clinical practice to satisfy the thesis of an inseparable union
      between gaining knowledge and cure. He ends by challenging the core of the
      psychoanalytic theory of change, arguing that it neither does justice to the
      practice of psychoanalysts nor to contemporary knowledge of processes and
      mechanisms of therapeutic change. Finally, he proposes that we detach practice
      from theory, in order to study the former in its own merits, utilising a
      plurality of methods ranging from systematic investigation to the recent
      methodology of the Working Party.

PMID- 19382959
TI  - Problems of collegial learning in psychoanalysis: narcissism and curiosity.
AB  - Despite clinical sensitivity when listening to patients, analysts have not fared
      well in hearing and talking to each other with respectful open-mindedness.
      Underlying factors are considered with particular focus on the interplay between
      self-aimed forces of narcissism and outward-aimed forces of curiosity. Included
      in examination of problems of collegial communication are limitations
      structurally inherent to the human mind (such as the need to abstract aspects of
      experience in order to focus attention plus the mind's tendency to categorical
      thinking), those derived from individual psychology (such as vulnerability of
      self-esteem), and those related to group dynamics (such as the problems attendant
      to new ideas and the allegiances they stir, parochialism and the development of
      radical schools, the competitiveness between schools). The contribution of
      cultural influences and the multiply determined uses of language are also
      highlighted. The core sense of smallness in the strangeness of the universe and
      in the presence of others is seen as a common thread.

PMID- 19382960
TI  - The death drive: conceptual analysis and relevance in the Spanish psychoanalytic
      community.
AB  - Based on a six-year doctoral research, the author carries out a historical,
      epistemological and paradigmatic assessment of the controversial concept of the
      death instinct. The author analyses this notion's speculative nature; its
      relation with the second principle of thermodynamics; the feasibility of a return
      to an inorganic state; the death drive's metaphorical and isomorphic uses, as
      well as its theoretical and doctrinaire approaches; its relationship with
      repetition compulsion and masochism; the influence of Freud 's scientific
      background on its formulation; and its context-dependent meaning. Although this
      paper stems mainly from the theoretical aspects of the study, it also offers some
      clinical thoughts on the basis of a clinical vignette. The author stresses the
      underlying healing aspects of repetition in the analytic situation. Next, he
      presents concise comments on his empirical research on the current professional
      usage of the death drive in the Spanish psychoanalytical community. This research
      covered more than 27% of Spanish psychoanalysts (IPA) and psychotherapists
      (EFPP). The essay's conclusions point to the ambiguous character of the death
      drive concept and its literal unacceptability and the absence of consistent
      arguments for its acceptance.

PMID- 19382961
TI  - Truth as a way of developing and preserving the space for thinking in the minds
      of the patient and the analyst.
AB  - Clinical material from the analysis of a young patient diagnosed with borderline
      personality disorder and heavily dependent on drugs was examined to identify
      changes in setting that may be necessary to enable the psychoanalytical treatment
      of this type of patient. The article describes a lack of truth in the patient's
      life and the absence of a good enough space for thinking in her mind. In order to
      enhance the development of the capacity for symbolization in the patient's mind,
      the analyst had to become an object the patient needed. In order to do this the
      analyst had to manage setting alteration. Theoretical frameworks proposed by
      Ferenczi, Winnicott and Bion were used to guide the psychoanalyst's approach to
      this patient. The survival of the capacity for thinking psychoanalytically inside
      the analyst's mind when the setting has been significantly distorted by the
      disruptive behavior of the patient is guaranteed by the trueness of their link.
      It is suggested that maybe this is decisive for a successful psychoanalytical
      treatment of this type of patient.

PMID- 19382962
TI  - On becoming a psychoanalyst.
AB  - One has the opportunity and responsibility to become an analyst in one's own
      terms in the course of the years of practice that follow the completion of formal
      analytic training. The authors discuss their understanding of some of the
      maturational experiences that have contributed to their becoming analysts in
      their own terms. They believe that the most important element in the process of
      their maturation as analysts has been the development of the capacity to make use
      of what is unique and idiosyncratic to each of them; each, when at his best,
      conducts himself as an analyst in a way that reflects his own analytic style; his
      own way of being with, and talking with, his patients; his own form of the
      practice of psychoanalysis. The types of maturational experiences that the
      authors examine include situations in which they have learned to listen to
      themselves speak with their patients and, in so doing, begin to develop a voice
      of their own; experiences of growth that have occurred in the context of
      presenting clinical material to a consultant; making self-analytic use of their
      experience with their patients; creating/discovering themselves as analysts in
      the experience of analytic writing (with particular attention paid to the
      maturational experience involved in writing the current paper); and responding to
      a need to keep changing, to be original in their thinking and behavior as
      analysts.

PMID- 19382964
TI  - Is truth an illusion? Psychoanalysis and postmodernism.

PMID- 19382965
TI  - Truth, human relatedness, and the analytic process: an interpersonal/relational
      perspective.

PMID- 19382966
TI  - On truth and clinical psychoanalysis.

PMID- 19382967
TI  - On: the concept of therapeutic regression: in response to Laurence Spurling.

PMID- 19382968
TI  - On: unraveling the riddle of exhibitionism.

PMID- 19382971
TI  - On: repression and splitting: towards a method of conceptual comparison.

PMID- 19382973
TI  - The transformation of sociogenic autistic defences in The Lives of Others.

PMID- 19382983
TI  - Food allergy in adolescents and adults.
AB  - There has been an increase in the prevalence of food allergy in the last few
      decades. Adult food allergy may represent persistence of reactions that commenced
      in infancy and early childhood or it may be initiated in adulthood through new
      sensitizations. Persistence of peanut allergy is an example of the former
      situation. Approximately 20% of children will develop tolerance to peanuts, so
      there will be an increasing number of individuals reaching adulthood where this
      problem will need ongoing management. In addition to peanut, tree nuts, fruits,
      vegetables and seafood are implicated as common causes of food allergy in
      adulthood. Sensitization may occur directly to a food allergen or indirectly
      through cross-reactivity with an aeroallergen. Adults may present with a spectrum
      of clinical manifestations from oral allergy syndrome to fatal anaphylaxis. The
      management of food allergy consists of appropriate education regarding avoidance
      of implicated foods, modifying potential risk factors for anaphylaxis, such as
      asthma and prompt recognition and treatment of acute reactions.

PMID- 19382984
TI  - Reversible posterior leucoencephalopathy syndrome associated with sunitinib.

PMID- 19382985
TI  - Disease mongering: the overlooked legs.

PMID- 19382986
TI  - 'Disease mongering' and the evidence.

PMID- 19382987
TI  - A patient-focused business model: contradiction in terms?

PMID- 19382989
TI  - Improving client-centred care and services: the role of front/back-office
      configurations.
AB  - AIM: This paper is a report of a study conducted to explore the application of
      designing front- and back-office work resulting in efficient client-centred care
      in healthcare organizations that supply home care, welfare and domestic services.
      BACKGROUND: Front/back-office configurations reflect a neglected domain of design
      decisions in the development of more client-centred processes and structures
      without incurring major cost increases. METHOD: Based on a literature search, a
      framework of four front/back-office configurations was constructed. To illustrate
      the usefulness of this framework, a single, longitudinal case study was performed
      in a large organization, which provides home care, welfare and domestic services
      for a sustained period (2005-2006). FINDINGS: The case study illustrates how
      front/back-office design decisions are related to the complexity of the clients'
      demands and the strategic objectives of an organization. The constructed
      framework guides the practical development of front/back-office designs, and
      shows how each design contributes differently to such performance objectives as
      quality, speed and efficiency. CONCLUSIONS: The front/back-office configurations
      presented comprise an important first step in elaborating client-centred care and
      service provision to the operational level. It helps healthcare organizations to
      become more responsive and to provide efficient client-centred care and services
      when approaching demand in a well-tuned manner. In addition to its applicability
      in home care, we believe that a deliberate front/back-office configuration also
      has potential in other fields of health care.

PMID- 19382990
TI  - Introduction: Autoimmune polyendocrine syndrome type 1 (APS-1): a rare monogenic
      disorder as a model to improve understanding of tolerance and autoimmunity.

PMID- 19382991
TI  - Clinical manifestations and management of patients with autoimmune polyendocrine
      syndrome type I.
AB  - Autoimmune polyendocrine syndrome type I (APS-I) is a monogenic model disease of
      autoimmunity. Its hallmarks are chronic mucocutaneous candidosis,
      hypoparathyroidism and adrenal insufficiency, but many other autoimmune disease
      components occur less frequently. The first components usually appear in
      childhood, but may be delayed to adolescence or early adult life. There is
      enormous variation in presentation and phenotype, which makes the diagnosis
      difficult. Antibodies against interferon-omega and -alpha have recently been
      shown to be sensitive and relatively specific markers for APS-I, and mutational
      analysis of the autoimmune regulator gene gives the diagnosis in >95% of cases.
      The treatment and follow-up of patients is demanding and requires the
      collaboration of specialists of several fields. However, the literature is
      especially sparse regarding information on treatment and follow-up; hence, we
      present here a comprehensive overview on clinical characteristics, treatment and
      follow-up based on personal experience and published studies.

PMID- 19382992
TI  - Autoimmune polyendocrine syndrome type 1 (APS-1) as a model for understanding
      autoimmune polyendocrine syndrome type 2 (APS-2).
AB  - Autoimmune polyendocrine syndromes type 1 and 2 (APS-1 and APS-2) are diverse in
      regards to their component diseases and immunologic features of pathogenesis.
      Animal models and human studies highlight the importance of alleles of HLA (human
      leukocyte antigen)-like molecules determining tissue specific targeting that with
      the loss of tolerance leads to organ specific autoimmunity. Knowledge of the
      syndromes and component diseases allows clinicians to recognize and prevent
      illness prior to morbidity. With the current understanding of the syndromes, a
      paradigm for diagnosis, screening and treatment can be established. Once
      genetically susceptible individuals are identified screening for autoantibodies
      can be performed. Amongst autoantibody positive individuals, monitoring for
      physiologic decompensation, with a goal of treating prior to morbidity and in
      some cases mortality, follows. With continued basic and clinical research,
      therapies aimed at treating the underlying autoimmunity and disease prevention
      should become possible.

PMID- 19382993
TI  - Learning to be tolerant: how T cells keep out of trouble.
AB  - A pool of immature T cells with a seemingly unrestricted repertoire of antigen
      specificities is generated life-long in the thymus. Amongst these cells are,
      however, thymocytes that express a strongly self-reactive antigen receptor and
      hence hold the potential to trigger autoimmunity. To prevent such an outcome, the
      thymus employs several independent but functionally related strategies that act
      in parallel to enforce self-tolerance. The deletion of strongly self-reactive
      thymocytes and the generation of regulatory T cells constitute the two most
      efficient mechanisms to induce and maintain immunological tolerance. Thymic
      epithelial cells of the medulla express for this purpose tissue-restricted self
      antigens. This review will focus on the cellular and molecular mechanisms
      operative in the thymus to shape a repertoire of mature T cells tolerant to self
      antigens.

PMID- 19382995
TI  - Changes of psychiatric parameters and their relationships by oral isotretinoin in
      acne patients.
AB  - Oral isotretinoin is a highly effective agent for the treatment of moderate to
      severe acne, but ever since oral isotretinoin was introduced as a modality for
      acne, the relationship between oral isotretinoin therapy and psychiatric
      problems, especially depression, has been controversial. The purposes of this
      study were to know the acute effects of oral isotretinoin therapy on psychiatric
      symptoms and to investigate the relationships among them, which have not been
      reported in the published work. This cohort study included 38 acne patients who
      started oral isotretinoin therapy. Individual patients were examined before
      administering oral isotretinoin and 2 and 8 weeks after commencement. Acne
      severity was graded using the Leeds revised acne grading system. Acute
      psychiatric effects of oral isotretinoin were assessed using a questionnaire
      authorized by two psychiatrists. This questionnaire included assessments of acne
      related quality of life (Assessment of the Psychological and Social Effects of
      Acne [APSEA]), depression (Beck's depression inventory [BDI]), anxiety (Beck's
      anxiety inventory [BAI]) and psychopathology (Symptomchecklist-90-revised [SCL-90
      R]). Acne grading and APSEA showed similar change patterns. Both improved after 8
      weeks of oral isotretinoin treatment. On the other hand, the severity of
      depression decreased after 2 weeks of treatment. A significant correlation was
      found between BDI and APSEA, but no correlation was found between BDI and acne
      grade. These results indicate that oral isotretinoin therapy alleviates
      depressive symptoms. Improvements in depression are directly related to acne
      related life quality improvements rather than to improvement in acne grade.

PMID- 19382996
TI  - Ocular alterations in patients of alopecia areata.
AB  - There is paucity of published work on ocular alterations in patients of alopecia
      areata (AA), especially from the Asian continent. We studied the clinical profile
      of 83 patients of AA and 80 sex- and age-matched controls to assess and compare
      the ocular changes, namely punctate opacities, cataract, intraocular tension and
      retinal changes. The outcome was analyzed with respect to prevalence of atopy,
      concomitant personal or family history of autoimmune diseases and nail changes in
      both the groups. The prevalence of atopy and family history of autoimmune
      diseases was significantly higher in the patient group. Lenticular changes were
      observed in 40.9% patients (including cataract in 16.9%) and 11.2% controls (P <
      0.005). Within the patient group, lenticular involvement occurred with increased
      frequency in atopics (P = 0.034) and in the presence of family history of
      autoimmune diseases (P < 0.05). Retinal changes in the form of degenerative
      changes, pigmentary clumping and abnormal vascular changes were more prevalent (P
      < 0.001) in the study group. As the ocular changes were not found to correlate
      with the age, severity or extent of the disease, an initial ophthalmological
      screening of all patients is suggested.

PMID- 19382997
TI  - Evaluation of polymerase chain reaction-based detection of Mycobacterium leprae
      for the diagnosis of leprosy.
AB  - Because Mycobacterium leprae cannot be cultivated in vitro, laboratory diagnosis
      of leprosy is generally made by microscopic and histopathological examination.
      The objective of the present study was to evaluate the sensitivity and utility of
      polymerase chain reaction (PCR) to detect M. leprae in comparison with other
      conventional methods for diagnosis such as split skin smears, histopathology and
      serodiagnosis. PCR amplification of the M. leprae-specific 16S ribosomal RNA was
      compared to other methods. Samples included 37 multibacillary (MB) patients with
      a positive bacteriological index (BI), 32 newly diagnosed paucibacillary (PB)
      patients whose BI were negative and 30 plaque psoriasis patients not residing in
      leprosy endemic areas as controls. The sensitivity of PCR was 30 fg of M. leprae
      DNA, which is equivalent to the DNA from 8.3 bacilli. The detection rate in MB
      and PB were 100% and 50%, respectively; the specificity was 100%.
      Semiquantitative evaluation of PCR correlated well with BI, but not with the
      morphological index (MI) nor with the serum antibody against phenolic glycolipid
      1 (PGL-1). PCR detection of M. leprae targeting 16S ribosomal RNA was specific
      and more sensitive than conventional methods, and can contribute to early and
      accurate diagnosis of leprosy.

PMID- 19382998
TI  - Severity factors of Mamushi (Agkistrodon blomhoffii) bite.
AB  - The factors determining the severity of a Mamushi (Agkistrodon blomhoffii) bite
      were analyzed based on the findings of our 34 cases and those appearing in the
      published work. It was not possible to forecast the final severity at the time of
      the patient's arrival and by the initial blood examination data. The maximal
      creatinine kinase (CK) values elevated proportionally with the time from the
      bite, and the relation approximated the equation of y = 300chi, where y
      represents the maximal CK value and chi indicates the time from the bite to the
      peak of CK level. In the severe cases which required intensive care, the level of
      the CK deviated remarkably from this line, and could be grossly distinguished
      from the non-severe cases. The maximal white blood cell (WBC) count also
      gradually increased in concordance with the time from the bite, and in addition,
      the WBC count of most of the severe cases exceeded 20,000/microL. This evidence
      suggests that the rate of the CK value elevation in relation to the time from the
      bite can be a useful indicator of the severity of a Mamushi bite, and the WBC
      count also reflects the severity.

PMID- 19382999
TI  - Rituximab-induced vasculitis: A case report and review of the medical published
      work.
AB  - Rituximab is an anti-CD20 chimeric murine/human monoclonal antibody mainly used
      in the treatment of patients with a cutaneous lymphoid malignancy. Among the side
      effects associated with rituximab administration, vasculitis has been rarely
      reported. There are two reported cases in the English language medical published
      work. We describe a 38-year-old Korean man with cutaneous vasculitis occurring 1
      day after rituximab administration.

PMID- 19383000
TI  - Autosomal recessive type 2 pseudoxanthoma elasticum presenting with generalized
      skin laxity.
AB  - Herein, we describe a sporadic case of recessive type 2 pseudoxanthoma elasticum.
      A 26-year-old woman without family history presented with cutis laxa-like marked
      wrinkling involving the whole-body and a serpiginous streak on the upper left
      arm. She denied any other systemic problems related to difficulty with visual
      acuity or vascular disease. A skin biopsy specimen from the loose skin showed the
      accumulation of calcified degenerated elastic fibers and foci of ossification in
      the dermis. Histopathological study from a serpiginous streak revealed
      mineralized debris that was eliminated through the epidermis, the finding
      consistent with elastosis perforans serpiginosa. Recessive type 2 pseudoxanthoma
      elasticum is very rare and the presenting case is interesting in that this
      patient presented with lesions of secondary ossification and elastosis perforans
      serpiginosa in association with pseudoxanthoma elasticum.

PMID- 19383001
TI  - Two cases of pyodermatitis-pyostomatitis vegetans.
AB  - Pyodermatitis-pyostomatitis vegetans (PPV) is a rare chronic pustular and
      vegetating mucocutaneous dermatosis. The oral lesions present as multiple,
      friable and yellowish pustules, which form "snail tracts" and rupture easily. The
      cutaneous lesions begin as crusted erythematous papulopustules that coalesce to
      form large vegetating plaques, usually in the axillae, genital area and scalp.
      Cutaneous lesions usually develop at the same time as the oral lesions or
      thereafter. PPV is usually considered as a specific marker for inflammatory bowel
      disease since the concurrence of PPV and inflammatory bowel disease has been
      reported in approximately 70% of cases. We report two patients who showed typical
      clinical and histopathological features of PPV, but were not accompanied by
      inflammatory bowel disease.

PMID- 19383002
TI  - Necrotizing fasciitis caused by Streptococcus pneumoniae.
AB  - A 69-year-old woman presented with shivering and pain in the lower extremities on
      5 April 2006; she was referred to the dermatology division of our hospital on the
      following day with difficulty in walking. She had been suffering from non-viral,
      non-alcoholic liver cirrhosis, and was being treated by the Division of Internal
      Medicine. Physical examination showed edema in the lower extremities and light
      purpuras on the groin and legs. Low blood pressure had been observed since
      admission. Necrotizing fasciitis (NF) was suspected on the basis of the skin
      symptoms, systemic conditions, and magnetic resonance imaging. During surgical
      debridement under general anesthesia, cardiopulmonary arrest occurred, and the
      patient died 12 h after admission. NF, in its early stages, exhibits few skin
      changes. In order to differentiate it from other skin infections, it is necessary
      to take into account blood pressure, abnormal systemic conditions, and severe
      pain out of proportion to its minor skin changes. In the present case,
      Streptococcus pneumoniae was detected by blood culture. Soft tissue infectious
      diseases caused by S. pneumoniae, especially NF, are very rare. We have reviewed
      reported cases of NF caused by S. pneumoniae.

PMID- 19383003
TI  - Neurofibromatosis type 1 associated with Charcot-Marie-Tooth type 1A.
AB  - Neurofibromatosis and Charcot-Marie-Tooth are genetic disorders of the nervous
      system affecting the development and growth of nerve cells and demyelination of
      peripheral neurons, respectively. We report a 22-year-old man who presented
      clinical manifestations of both neurofibromatosis type 1 (NF1) and Charcot-Marie
      Tooth type 1A. The simultaneous occurrence of neurofibromatosis and Charcot-Marie
      Tooth disease has rarely been reported. More extensive reports and further
      investigations of this combination will certainly provide a better understanding
      of this linkage in the near future.

PMID- 19383004
TI  - Spontaneous regression of Merkel cell carcinoma after biopsy.

PMID- 19383005
TI  - Successful oral cyclosporin therapy for Henoch-Schonlein purpura nephropathy.

PMID- 19383006
TI  - The utility of a nebulised intra-tracheal rat model of invasive pulmonary
      aspergillosis.
AB  - Invasive pulmonary aspergillosis (IPA) is of particular concern to
      immunodeficient patients, whose mortality rates may exceed 80%. The development
      of an animal model that faithfully reproduces the pathophysiology of IPA would
      improve the studies on diagnostic and therapeutic modes, and the use of rats as a
      possible model for IPA seems to have been largely overlooked. Such a model could
      be established with the MicroSprayer IA-1B. Male Sprague-Dawley rats (6-8 weeks
      old) were rendered immunodeficient by cyclophosphamide injections and a protein
      deficient diet. On day D0, they were anaesthetised by inhalation of 5% isoflurane
      and infected by the intra-tracheal aerosolization of 100 microl of an Aspergillus
      fumigatus spore suspension through a MicroSprayer IA-1B. This inoculation process
      was simple and rapid, with no deaths observed during or immediately after the
      procedure. The rats regained consciousness within 1 min. Follow-up data including
      those for clinical factors (weight changes, mortality rate), biological factors
      (Aspergillus antigens) and histological factors were consistent with previous
      studies. The advantages of this model include the ease of animal manipulation,
      the reproducibility of infection and the potential for repeated blood sampling.

PMID- 19383007
TI  - Food-bourne risks and Hurricane Katrina.

PMID- 19383009
TI  - Retraction. 'Chronic cardiac allograft rejection in mice is alleviated by
      inhibition of CCR5 in combination with cyclosporine'.

PMID- 19383010
TI  - Balancing between mental vulnerability and strength in daily life when suffering
      from eating difficulties.
AB  - The aim of this study was to explore the daily life experiences of women who
      suffer from eating difficulties (ED). The research question was: what mental
      challenges related to daily life are experienced by women who suffer from ED? ED
      challenge the daily lives of individuals and their families. The problem is often
      concealed, and the individuals concerned frequently experience guilt and shame.
      An explorative design was used. Five women participated in a group programme
      focusing on experiences of ED, guilt and shame, being a mother and self
      expression. Data were collected using focus group interviews and analysed by
      means of qualitative content analysis. The main theme Balancing between mental
      vulnerability and strength comprised three themes: (1) Struggling with emotional
      ambivalence; (2) Being cognitively aware of limitations; and (3) Experiencing an
      existential sense of being lost and frozen. The mental challenges were strong and
      affected the participants' lives. One clinical implication for psychiatric nurses
      is to acknowledge the strength of emotional, cognitive and existential challenges
      and make it possible for patients to articulate their exhaustion in spite of
      their outward appearance of strength.

PMID- 19383011
TI  - Fostering a culture of engagement: an evaluation of a 2-day training in solution
      focused brief therapy for mental health workers.
AB  - The focus of mental health care has changed considerably in recent years, from an
      almost exclusive inpatient system of care to one where the majority of care is
      being delivered within the community. Arguably this has contributed to a
      reduction in the length of inpatient admissions. Therefore, there is a need to
      understand the ramifications that shorter admissions have on inpatient care and
      nursing practice. This paper reports on a study designed to test the knowledge
      and skill acquisition and self-reported application of solution-focused brief
      therapy by staff following a 2-day training. The study adopted a repeated
      measures design where participants' baseline knowledge was measured prior to the
      2-day training and then at 3 and 6 months post-training. This study has
      demonstrated that the 2-day training was effective in increasing participants'
      reported knowledge and understanding of solution-focused brief therapy and their
      self-reported use of the techniques in routine clinical practice. In conclusion,
      this study has established that staff from a variety of professional and non
      professional backgrounds can make good skill acquisition from a fairly modest
      training. Additionally, the current study has also highlighted the need for well
      conducted large-scale trials of this potentially important technology.

PMID- 19383012
TI  - Mental health nursing students' experience of stress: burdened by a heavy load.
AB  - This paper reports research outcomes of a study into personal stress experienced
      by mental health student nurses undertaking a diploma programme in Ireland. It
      uses a phenomenological research approach. The sample was purposive and involved
      in-depth interviews with six students. The purpose of the study was to contribute
      to the knowledge of the impact of personal life stressors. Findings from this
      study focus on the following themes: event, meaning, effects, ability to move
      beyond the stress, influence on life and constraints and demands. Key points
      arising are that the stress experience does impact students' internal and
      external worlds, potentially lessening functioning and inhibiting growth and
      development. This paper presents student narratives that offer insights into
      their inner worlds, providing true accounts of the essence of stress for them.
      This knowledge has implications for lecturers, personal tutors, nurse
      educationalists and nursing curricula, highlighting need for more proactive
      approaches to the provision of guidance on professional support for students and
      staff. Insights derived from this study are relevant not only to mental health
      nurse education but also to academic staff delivering professional education
      programmes to healthcare practitioners in a variety of settings.

PMID- 19383013
TI  - University students' suicidal thoughts and influencing factors.
AB  - This research was planned as a descriptive study for the purpose of examining the
      suicidal thoughts of first-year university students and the factors that might
      affect them. The research was conducted with the participation of first-year
      students (class of 1992) at Ege University between January 2003 and October 2004.
      The research data were collected on a form prepared by the researcher to
      determine the university students' socio-demographic characteristics and their
      suicidal thoughts, the trait anger, expression of anger inventory and the brief
      symptom inventory. It was determined that 2.4% of the students had suicidal
      thoughts, and 11.2% of the students had previously attempted suicide. The risk
      factors of the students' suicidal thoughts were determined to be issues of
      gender, school problems, family relationships, anger expression, somatization,
      hostility, psychotic symptoms, phobic anxiety, anxiety disorder and interpersonal
      sensitivity.

PMID- 19383014
TI  - Oral medication management in inpatient psychiatric care in Turkey.
AB  - The aim of this study was to describe current status of oral medication
      management and related situations by nurses who work on psychiatric wards in
      Turkey. The study was performed in 34 psychiatric wards in Turkey, and 471 nurses
      agreed to participate in the study. Data were collected by a questionnaire. In
      our study, it was determined that one quarter of the nurses do not collect data
      about past medication history of the patient before giving medications, and 59.7%
      of the nurses checked all the patients' mouths after each pill was given. The
      orders are checked by 80.5% of the nurses every day. The leading patient reaction
      nurses face during medication administration was refusal to take the medication.
      The nurses stated that they first informed the physician without making any
      intervention on patients who did not take their pills. The nurses primarily
      observed the patient to evaluate the effect of a medication (84.3%) and, with a
      similar percent (82.8%), the side effects of a medication. In conclusion,
      continuing education, certification and post-graduated courses is provided for
      nurses about their other roles and responsibilities as well as increasing the
      quality of oral medication administration which is a difficult area.

PMID- 19383015
TI  - Assessing parenting capacity: are mental health nurses prepared for this role?
AB  - Mental health nurses in the UK are involved in the assessment of the parenting
      capacity of mothers with a serious mental illness in psychiatric facilities.
      There is evidence that child and family social workers, as the frontline
      professionals in safeguarding children, rely heavily on the mental health
      parenting assessment. Parenting assessments have potentially major implications
      for mother and baby and can lead to the separation of mother and baby. However,
      there is little or no provision for mental health nurses to undertake this role.
      In the UK, as in many other countries, there is currently no data as to which
      psychiatric facilities are conducting parenting assessments nor about the quality
      of the assessment. There are significant tensions for mental health nurses
      undertaking parenting assessments and there is no specific training for the role.
      This paper challenges existing practice, highlights the need for an audit of the
      current services and recommends the development of a recognized training
      programme.

PMID- 19383016
TI  - Evidence-based practice and the need for paradigmatic pluralism in cognitive
      behavioural psychotherapy.
AB  - The scientist-practitioner model, which is based on positivistic methodological
      assumptions, is influential in the development, training and practice of
      cognitive behavioural psychotherapists. As the emergence of 'Nurse Cognitive
      Behavioural Therapist' training in the early 1970s in Britain, many of those
      trained have been mental health nurses and with the emergence of the Increased
      Access to Psychological Therapies agenda many more are likely to undergo
      training. Despite some acceptance of its relevance, the scientist-practitioner
      model is subject of criticism on the grounds of its achievability and
      contemporary relevance, and its exclusion of other modalities of counselling and
      psychotherapy without an, as yet, disseminated evidence base. In line with key
      policy-related work, the empirical and political issues inscribed within the
      scientist-practitioner model have direct implications for the educational
      preparation and ongoing professional development of cognitive behavioural
      practitioners. Specifically, in this polemical paper it is argued that there is a
      moral and educational need for 'senior' practitioners to question the philosophy
      of science assumptions underpinning the overwhelming dominance of the
      quantitative-experimental approach in cognitive behavioural psychotherapy. Such a
      critically evaluative and pluralistic stance would arguably distinguish senior
      practitioners in terms of them being able to make broad rather than narrow
      appraisals of the evidence base for their practice. A recognition of the
      relevance of paradigmatic and epistemological pluralism in cognitive behavioural
      work would, it is argued, confer considerable advantages on our practice
      communities and clients. A range of emerging implications for cognitive
      behavioural education, practice and relational ethics are described and
      discussed.

PMID- 19383017
TI  - Physical intervention trainers: the case for greater accountability.
AB  - Physical intervention training courses are commonplace events in psychiatric and
      mental healthcare settings across the UK. While there is still debate as to what
      techniques should be taught on such courses, there is good evidence as to the
      mechanisms whereby pain, injury and even death can be inflicted. There is also a
      wealth of literature identifying how organizational culture can influence the
      quality of service delivery and standards of client care. It is well documented
      that the dignity, well-being and physical integrity of service users can be
      compromised by staff acts and omissions stemming from corrupted cultures. What
      has not been explored in detail to date is the role of physical intervention
      trainer, specifically the values they model and how these may influence the
      readiness with which staff resort to physical restraint strategies. It is
      possible that even approved physical techniques can become compromised through
      poor training technique and expose end recipients to needless humiliation and
      potential harm. This paper discusses this area of practice, offers insight on how
      the learning process is compromised by trainers and suggests areas for future
      research.

PMID- 19383018
TI  - Touch in mental health nursing: an exploratory study of nurses' views and
      perceptions.
AB  - The aim of this study was to explore psychiatric nurses' perceptions of physical
      touch with people who experience mental health problems. A descriptive
      exploratory qualitative research design was used. Semi-structured interviews were
      carried out with 10 registered psychiatric nurses who met the inclusion criteria
      and were randomly selected to participate in the study. Burnard's 14 stage-by
      stage process of coding and categorization was used to analyse the data. Watson
      distinguished between two kinds of physical touch: instrumental and expressive.
      The findings indicated that physical touch was used in mental health nursing;
      however, it was only considered to be therapeutic to clients if used judiciously,
      with effective interpersonal skills. The participants in this study clearly
      identified the need to be sensitive to both the individual client needs, and
      honour their personal space and cultural background. A significant issue in this
      study was male participants concerns that touching female clients would be
      misinterpreted as a sexual advance. To protect themselves, male participants used
      touch in a cautious and minimal manner, and only in a public space, where others
      could view the interaction. In the absence of research on physical touch in
      mental health nursing there is a need for further research to explore in detail
      these findings.

PMID- 19383019
TI  - The convenient myth of 'good scholarship'.

PMID- 19383020
TI  - The manual handling of the aggressive patient: a review of the risk of injury to
      nurses.
AB  - Staff are injured more frequently than patients during the implementation of
      physical interventions. In essence the application of physical interventions is a
      form of manual handling, where the aggressive patient is the 'load'. In the non
      mental healthcare environment, manual handling contributes to a large chunk of
      work-related musculoskeletal disorders. Applying physical interventions against
      an agitated and aggressive human load is a risk factor for injuries being
      sustained. This paper discusses physical interventions as a manual handling
      procedure as a possible explanation of injuries sustained to nursing staff from
      being in a team applying physical interventions. Possible strategies to reduce
      the risk of developing musculoskeletal disorders from physical interventions are
      discussed.

PMID- 19383021
TI  - Poor maternal mental health and trauma as risk factors for a short interpregnancy
      interval among adolescent mothers.

PMID- 19383025
TI  - Scientific rationale for the Finnish Allergy Programme 2008-2018: emphasis on
      prevention and endorsing tolerance.
AB  - In similarity to many other western countries, the burden of allergic diseases in
      Finland is high. Studies worldwide have shown that an environment rich in
      microbes in early life reduces the subsequent risk of developing allergic
      diseases. Along with urbanization, such exposure has dramatically reduced, both
      in terms of diversity and quantity. Continuous stimulation of the immune system
      by environmental saprophytes via the skin, respiratory tract and gut appears to
      be necessary for activation of the regulatory network including regulatory T
      cells and dendritic cells. Substantial evidence now shows that the balance
      between allergy and tolerance is dependent on regulatory T-cells. Tolerance
      induced by allergen-specific regulatory T-cells appears to be the normal
      immunological response to allergens in non atopic healthy individuals. Healthy
      subjects have an intact functional allergen-specific regulatory T-cell response,
      which in allergic subjects is impaired. Evidence on this exists with respect to
      atopic dermatitis, contact dermatitis, allergic rhinitis and asthma. Restoration
      of impaired allergen-specific regulatory T-cell response and tolerance induction
      has furthermore been demonstrated during allergen-specific subcutaneous and
      sublingual immunotherapy and is crucial for good therapeutic outcome. However,
      tolerance can also be strengthened unspecifically by simple means, e.g. by
      consuming farm milk and spending time in nature. Results so far obtained from
      animal models indicate that it is possible to restore tolerance by administering
      the allergen in certain circumstances both locally and systemically. It has
      become increasingly clear that continuous exposure to microbial antigens as well
      as allergens in foodstuffs and the environment is decisive, and excessive antigen
      avoidance can be harmful and weaken or even prevent the development of regulatory
      mechanisms. Success in the Finnish Asthma Programme was an encouraging example of
      how it is possible to reduce both the costs and morbidity of asthma. The time, in
      the wake of the Asthma Programme, is now opportune for a national allergy
      programme, particularly as in the past few years, fundamentally more essential
      data on tolerance and its mechanisms have been published. In this review, the
      scientific rationale for the Finnish Allergy Programme 2008-2018 is outlined. The
      focus is on tolerance and how to endorse tolerance at the population level.

PMID- 19383026
TI  - Interleukin-12 family members and type I interferons in Th17-mediated
      inflammatory disorders.
AB  - Cytokines produced by antigen-presenting cells govern the fate of helper T-cell
      responses. Herein, we review the impact of interleukin (IL)-23 and IL-27 on the
      outcome of T-helper (Th) 17 cell responses and discuss their impact in the
      pathogenesis of T-cell-mediated inflammatory disorders of autoimmune or allergic
      origin. We then discuss how type I interferons might influence the course of
      autoimmune diseases by tipping the balance between IL-12 family members.

PMID- 19383027
TI  - Nasal endothelial interleukin-10 expression is negatively correlated with nasal
      symptoms after allergen provocation.
AB  - BACKGROUND: Despite major efforts, factors that predict or correspond to the
      level of allergic symptoms remain elusive. Given our previous observations of
      mucosal interleukin-10 (IL-10) expression by local tissue cells and its described
      role as immune modulator, we hypothesized that, in allergic rhinitis, nasal
      mucosal IL-10 expression could influence the severity of symptoms. METHODS: In
      this study, we investigated endothelial IL-10 expression in nasal mucosa of
      healthy- and house dust mite allergic patients, both before and after
      provocation, and under nasal steroid therapy. Nasal turbinate biopsies were taken
      from healthy individuals as well as from house dust mite allergic patients, both
      before and after provocation. Allergic patients received fluticasone proprionate
      aqueous nasal spray or control treatment. In the allergic patients, endothelial
      IL-10 scores based on immunohistochemical stainings were correlated with allergic
      symptoms, measured by visual analog scores. RESULTS: At baseline, variable levels
      of endothelial IL-10 were detected in nasal biopsies. After nasal provocation,
      but not at baseline, endothelial IL-10 expression corresponded very closely to
      the allergic symptoms after allergen provocation. Low symptom scores were
      correlated with high endothelial IL-10 scores. This correlation disappeared after
      fluticason propionate treatment. CONCLUSIONS: There is a large variation in the
      level of endothelial IL-10 expression both in healthy individuals and in house
      dust mite allergic patients. Endothelial IL-10 expression may affect local immune
      reactions resulting in reduced levels of allergic symptoms.

PMID- 19383029
TI  - Activity of triptolide against human mast cells harboring the kinase domain
      mutant KIT.
AB  - Gain-of-function mutations of the receptor tyrosine kinase KIT can cause systemic
      mastocytosis (SM) and gastrointestinal stromal tumors. Most of the constitutively
      active KIT can be inhibited by imatinib; D816V KIT cannot. In this study, we
      investigated the activity of triptolide, a diterpenoid isolated from the Chinese
      herb Tripterygium wilfordii Hook. f., in cells expressing mutant KIT, including
      D816V KIT. Imatinib-sensitive HMC-1.1 cells harboring the mutation V560G in the
      juxtamembrane domain of KIT, imatinib-resistant HMC-1.2 cells harboring both
      V560G and D816V mutations, and murine P815 cells, were treated with triptolide,
      and analyzed in terms of growth, apoptosis, and signal transduction. The in vivo
      antitumor activity was evaluated by using the nude mouse xenograft model. Our
      results demonstrated that triptolide potently inhibits the growth of both human
      and murine mast cells harboring not only imatinib-sensitive KIT mutation but also
      imatinib-resistant D816V KIT. Triptolide markedly inhibited KIT mRNA levels and
      strikingly reduced the levels of phosphorylated and total Stat3, Akt, and Erk1/2,
      downstream targets of KIT. Triptolide triggered apoptosis by inducing
      depolarization of mitochondrial potential and release of cytochrome c,
      downregulation of Mcl-1 and XIAP. Furthermore, triptolide significantly abrogated
      the growth of imatinib-resistant HMC-1.2 cell xenografts in nude mice and
      decreased KIT expression in xenografts. Our data demonstrate that triptolide
      inhibits imatinib-resistant mast cells harboring D816V KIT. Further investigation
      of triptolide for treatment of human neoplasms driven by gain-of-function KIT
      mutations is warranted.

PMID- 19383030
TI  - Visceral fat loss induced by a low-calorie diet: a direct comparison between
      women and men.
AB  - AIM: No studies have assessed if changes in visceral adipose tissue (VAT) during
      weight loss differ between women and men with comparable amounts of VAT at
      baseline. The aim of this study was to assess if changes in VAT induced by a low
      calorie diet (LCD) differ between women and men. METHODS: In this post hoc
      analysis of an existing database, abdominal adipose tissue was evaluated before
      and after an 8-week LCD (800-1000 kcal/day) by a single-slice magnetic resonance
      scan performed at the abdominal level. Body composition was measured by dual X
      ray energy absorptiometry. RESULTS: Data from 111 obese subjects (85 women and 26
      men) were available. Relative changes in VAT were found to be more pronounced in
      men [mean (95% CI): -32.6% (-38.7 to -26.6)] than in women [-21.9% (-25.0 to 
      18.8)] (p = 0.003) after correction for relative changes in fat mass (FM). When
      analysing only the data from a subgroup of 23 women and 23 men who were matched
      for similar visceral to abdominal subcutaneous fat ratio at baseline, these
      differences could not be observed anymore: the change in VAT was -33.7% (-38.7 to
      -28.7) in men and -26.8% (-31.8 to -21.8) in women (p = 0.07). CONCLUSIONS: This
      study suggests that relative changes in VAT during a LCD may be greater in men
      than in women even after taking relative changes in FM into account. However,
      these differences disappear when properly matching the subjects for baseline
      amounts of VAT.

PMID- 19383031
TI  - Prodrug delivery of novel PTP1B inhibitors to enhance insulin signalling.
AB  - A growing percentage of the population is resistant to two key hormones - insulin
      and leptin - as a result of increased obesity, often leading to significant
      health consequences such as type 2 diabetes. Protein tyrosine phosphatase 1B
      (PTP1B) is a key negative regulator of signalling by both of these hormones, so
      that inhibitors of this enzyme may provide promise for correcting endocrine
      abnormalities in both diabetes and obesity. As with other tyrosine phosphatases,
      identification of viable drug candidates targeting PTP1B has been elusive because
      of the nature of its active site. Beginning with novel phosphotyrosine mimetics,
      we have designed some of the most potent PTP1B inhibitors. However, their highly
      acidic structures limit intrinsic permeability and pharmacokinetics. Ester
      prodrugs of these inhibitors improve their drug-like properties with the goal of
      delivering these nanomolar inhibitors to the cytoplasm of cells within target
      tissues. In addition to identifying prodrugs that is able to deliver active drugs
      into cells to inhibit PTP1B and increase insulin signalling, these compounds were
      further modified to gain a variety of cleavage properties for targeting activity
      in vivo. One such prodrug candidate improved insulin sensitivity in ob/ob mice,
      with lowered fasting blood glucose levels seen in the context of lowered fasting
      insulin levels following 4 days of intraperitoneal dosing. The results presented
      in this study highlight the potential for design of orally active drug candidates
      targeting PTP1B, while also delineating the considerable challenges remaining.

PMID- 19383032
TI  - Long-term 2-year safety and efficacy of vildagliptin compared with rosiglitazone
      in drug-naive patients with type 2 diabetes mellitus.
AB  - AIMS: To assess the long-term safety and the sustained glycaemic control of
      vildagliptin compared with rosiglitazone over 2-year treatment in drug-naive type
      2 diabetes mellitus patients. METHODS: This was an additional 80-week,
      multicentre, double-blind and active-controlled extension to a 24-week core study
      comparing the treatments of vildagliptin (50 mg b.i.d., n = 396) to rosiglitazone
      (8 mg q.d., n = 202). The primary efficacy variable was the mean change in
      haemoglobin A1c (HbA1c) from the core study baseline (day 1) to the end of 104
      weeks (the extension endpoint). RESULTS: Vildagliptin and rosiglitazone showed
      statistically significant and sustained HbA1c reductions from a core mean
      baseline of 8.6 and 8.7% to 7.8 and 7.3% respectively (both significant, p <
      0.001). However, rosiglitazone-treated patients showed significantly greater mean
      HbA1c reductions (mean difference 0.62%, s.e. 0.13, p < 0.001) compared with
      vildagliptin. The overall lipid profile significantly improved with vildagliptin
      compared to rosiglitazone treatment. Body weight remained unchanged in
      vildagliptin-treated patients despite improvements in glycaemic control but
      significantly increased (mean change from core study baseline 4.67 kg) in
      rosiglitazone-treated patients (p < 0.001). Notably, a lower incidence of
      peripheral oedema was seen with vildagliptin (4.6%) compared with rosiglitazone
      treatment (11.1%). More serious adverse events (SAEs) occurred in vildagliptin-
      than rosiglitazone-treated patients (12.5 and 9.1% respectively), but only one
      SAE each in both treatment group was suspected to be related to study drug. Three
      non-study drug-related deaths (vildagliptin: 2 and rosiglitazone: 1) were
      reported. Four mild hypoglycaemic events were observed with vildagliptin.
      CONCLUSIONS: This study showed that the similar short-term HbA1c reductions seen
      with both vildagliptin and rosiglitazone treatments were more durable after 104
      weeks of treatment with rosiglitazone than vildagliptin. However, this greater
      durability with rosiglitazone was at the expense of weight gain (almost 5 kg),
      higher incidences of peripheral oedema and a less favourable plasma lipid profile
      compared with vildagliptin.

PMID- 19383033
TI  - The emperor's tailors: the failure of the medical weight loss paradigm and its
      causal role in the obesity of America.
AB  - During the past century, the medical profession has developed a paradigm for the
      treatment of obesity, which prescribes specific exercise and dietary goals under
      the umbrella of 'lifestyle change'. It has three components, all of which evolved
      from origins that had nothing to do with weight control. First, it is
      individually prescriptive, that is weight loss is considered the responsibility
      of the individual as contrasted to a societal or group responsibility. Second, it
      recommends exercise aimed towards structured, or non-functional, activities with
      a variety of physiological endpoints. Last, dietary goals are defined by
      calories, exchanges, food groups and various nutritional components. Diets are
      usually grouped by these goals. This model is unique to America, it is not
      working and it has also played a causal role in the obesity it is attempting to
      eliminate. A new model must be developed, which contains an observationally based
      societal prescription and links activity with functional outcomes and diets,
      which are food rather than nutritionally based.

PMID- 19383034
TI  - Exenatide: a review from pharmacology to clinical practice.
AB  - BACKGROUND: Exenatide is an incretin mimetic that activates glucagon-like-peptide
      1 receptors. It blunts the postprandial rise of plasma glucose by increasing
      glucose-dependent insulin secretion, suppressing inappropriately high glucagon
      secretion and delaying gastric emptying. METHODS: In seven clinical trials
      performed in 2845 adult patients with type 2 diabetes mellitus who were
      inadequately controlled by a sulphonylurea and/or metformin (glycosylated
      haemoglobin, HbA1c <or=11%), or by thiazolidinediones (with or without metformin)
      and treated for periods from 16 weeks to 3 years, exenatide (5 microg b.i.d. s.c.
      for the first 4 weeks of treatment and 10 microg b.i.d. s.c. thereafter) reduced
      HbA1c, fasting and postprandial glucose, and body weight dose dependently, and
      was similar to insulin glargine and biphasic insulin aspart in reducing HbA1c.
      Body weight diminished with exenatide, whereas it increased with both insulin
      preparations. Positive effects on the lipid profile and a reduction in C-reactive
      protein were also recorded with exenatide. Treatment extensions up to 3 years
      showed that benefits were maintained in the long term. Adverse events were
      usually mild to moderate in intensity, and generally the frequency decreased with
      continued therapy. The most common was nausea (whose incidence may be reduced by
      gradual dose escalation from 5 microg b.i.d. to 10 microg b.i.d.), vomiting,
      diarrhoea, headache and hypoglycaemia (almost exclusively in patients treated
      with a sulphonylurea). RESULTS AND CONCLUSIONS: Exenatide is a new, promising
      therapeutic option for type 2 diabetic patients inadequately controlled by oral
      agents, before insulin therapy, offering the added benefits of body weight
      reduction and tight postprandial glucose control.

PMID- 19383035
TI  - Evidence for low-titre infections in insect symbiosis: Wolbachia in the bark
      beetle Pityogenes chalcographus (Coleoptera, Scolytinae).
AB  - Wolbachia are obligatory endosymbiotic alpha-proteobacteria found in many insect
      species. They are maternally transmitted and often exhibit reproductive
      phenotypes like cytoplasmic incompatibility. Pityogenes chalcographus is a bark
      beetle causing severe damage in spruce stands. Its European populations are
      divided into several mitochondrial clades separated by partial crossing barriers.
      In this study, we tested a large sample set covering the natural range of the
      beetle in Europe for the presence of Wolbachia and associations between infection
      pattern and mitotypes using a highly sensitive nested PCR technique. 35.5% of the
      individuals were infected with the endosymbiont and two distinct strains were
      identified. Both strains occur in low titre not accessible by conventional
      detection methods. The infections are present all over Europe, unlikely to cause
      the partial crossing barriers in this host and uncoupled from mitochondrial
      clades. This pattern is indicative for populations evolving towards endosymbiont
      loss and for repeated intraspecific horizontal transfer of Wolbachia.
      Alternatively, the low-titre infections found in P. chalcographus are yet another
      example for Wolbachia that can persist in host species at low densities and
      frequencies.

PMID- 19383036
TI  - Patterns of 15N assimilation and growth of methanotrophic ANME-2 archaea and
      sulfate-reducing bacteria within structured syntrophic consortia revealed by FISH
      SIMS.
AB  - Methane release from the oceans is controlled in large part by syntrophic
      interactions between anaerobic methanotrophic archaea (ANME) and sulfate-reducing
      bacteria (DSS), frequently found as organized consortia. An understanding of the
      specifics of this symbiotic relationship and the metabolic heterogeneity existing
      between and within individual methane-oxidizing aggregates is currently lacking.
      Here, we use the microanalytical method FISH-SIMS (fluorescence in situ
      hybridization-secondary ion mass spectrometry) to describe the physiological
      traits and anabolic activity of individual methanotrophic consortia, specifically
      tracking (15)N-labelled protein synthesis to examine the effects of organization
      and size on the metabolic activity of the syntrophic partners. Patterns of (15)N
      distribution within individual aggregates showed enhanced (15)N assimilation in
      ANME-2 cells relative to the co-associated DSS revealing a decoupling in anabolic
      activity between the partners. Protein synthesis in ANME-2 cells was sustained
      throughout the core of individual ANME-2/DSS consortia ranging in size range from
      4 to 20 MUm. This indicates that metabolic activity of the methane-oxidizing
      archaea is not limited to, or noticeably enhanced at the ANME-2/DSS boundary.
      Overall, the metabolic activity of both syntrophic partners within consortia was
      greater than activity measured in representatives of the ANME-2 and DSS observed
      alone, with smaller ANME-2/DSS aggregates displaying a tendency for greater (15)N
      uptake and doubling times ranging from 3 to 5 months. The combination of (15)N
      labelling and FISH-SIMS provides an important perspective on the extent of
      heterogeneity within methanotrophic aggregates and may aid in constraining
      predictive models of activity and growth by these syntrophic consortia.

PMID- 19383037
TI  - Cancer-related pain and quality of life in prostate cancer patients: assessment
      using the Functional Assessment of Prostate Cancer Therapy.
AB  - The objective of this study was to assess disease-associated pain and quality of
      life (QOL) in patients with prostate cancer (PC). A total of 102 PC patients
      (clinical stage B, C: 20, D2: 82) patients were enrolled. QOL was assessed using
      the Functional Assessment of Cancer Therapy, General and Prostate (FACT-G/P).
      Disease-specific pain response was assessed using the visual analog scale and the
      face rating scale. In patients with stage D2 PC, mean age, serum prostate
      specific antigen level, and performance status were 72.5 +/- 7.1 years (range, 55
      88), 217 +/- 467 ng/mL (range, 0.1-2600), and 1.4 (0-4), respectively. The score
      of physical well-being and FACT-P was significantly lower in stage D2 patients,
      compared with those of stage B/C (P = 0.02, 0.0088, respectively). Performance
      status, extent of disease, and the visual analog scale were related with a poor
      QOL score (P = 0.0054, 0.01, <0.0001, respectively). Thirty-two patients (39%)
      had disease-specific pain, and 25 patients received a related treatment. Ten
      patients under morphine analgesics maintained better QOL in almost all domains,
      compared with the seven patients without any painkillers. Combined use of FACT
      and pain scales enhances the objective assessment of QOL and pain status in PC
      patients. Control of disease-associated pain is crucial to improving QOL in stage
      D2 PC patients.

PMID- 19383038
TI  - Laparoscopic dismembered pyeloplasty for ureteropelvic junction obstruction in
      children.
AB  - OBJECTIVES: To present our initial experience with laparoscopic pyeloplasty and
      to evaluate the safety and short-term outcome of this technique in children.
      METHODS: Thirteen kidney units in twelve children underwent laparoscopic
      dismembered pyeloplasty for the management of ureteropelvic junction obstruction
      (UPJO) at our institution between 2005 and 2008. Patient age at surgery was 18
      177 months (mean 89.8 months). There were six boys and six girls. Ten had
      unilateral UPJO with a normal contralateral kidney, one had bilateral UPJO and
      one had UPJO of a solitary kidney. We used 3- and 5-mm instruments for grasping,
      blunt dissection, incising and suturing to facilitate safe and precise surgery.
      The outcome was measured by the operative time and resolution of obstruction and
      symptoms. RESULTS: Median operative time was 275 min (range 154-420). There was a
      slight relationship between age and operative time. No major perioperative
      complications occurred in any cases. Median renal pelvic anterior-posterior
      diameter at ultrasonography significantly decreased from 8.6 cm (range 3.8-22.0)
      preoperatively to 3.9 cm (1.0-8.9) postoperatively (P < 0.05). The median pre-
      and postoperative split renal function on diuretic renography in unilateral cases
      was 37.3% (range 29.7-46.4) and 39.5% (27.8-48.0), respectively. Overall,
      successful resolution of UPJO was observed in 12 of 13 kidneys (92.3%).
      CONCLUSIONS: Laparoscopic pyeloplasty represents a safe and effective option in
      the surgical treatment of children with UPJO.

PMID- 19383039
TI  - Role of antioxidants in the treatment of male infertility.
AB  - Male infertility continues to be a clinical challenge of increasing significance.
      While male factors such as decreased semen quality are responsible for 25% of all
      infertility issues, the etiology of suboptimal semen quality is poorly
      understood. Many physiological, environmental, and genetic factors have been
      implicated, including oxidative stress. Oxidative stress is induced by reactive
      oxygen species (ROS), or free radicals, and although ROS are required for
      critical aspects of sperm function, excessive levels of ROS can negatively impact
      sperm quality. The origin of ROS generation, and the etiologies of increased ROS
      in men with suboptimal sperm quality have only recently been elucidated, offering
      multiple targets for potential therapy. Here, we present a critical review of the
      literature describing the role of oxidative stress on decreased sperm function,
      as well as the role of antioxidants in the treatment of male factor infertility.

PMID- 19383040
TI  - A simplified approach to describe complex diffusers in displacement ventilation
      for CFD simulations.
AB  - With the capability to improve indoor air quality while simultaneously reducing
      energy demand, displacement ventilation is becoming popular. However, the
      numerical simulation of air distribution in an indoor space with displacement
      ventilation using computational fluid dynamics (CFD) is challenging because of
      the complexity of air diffuser geometry and the complicated airflow pattern
      generated. Typical air diffusers used for displacement ventilation systems
      include, but are not limited to, quarter-circular-perforated, grille, floor
      perforated, and swirl diffusers. None of them can be treated as a simple opening
      in CFD simulations because their effective area ratios are small. We have
      developed a new, simple method to describe those diffusers by directly specifying
      the correct jet momentum from the diffusers while adjusting the airflow rate by
      changing the effective areas. This is done by setting some CFD cells for a
      diffuser with a certain momentum, while other cells are randomly blocked. By
      implementing this method into a commercial CFD program, this study used the
      method to simulate air distributions in an office and a workshop with those
      diffusers under cooling or heating conditions. The distributions of air velocity,
      temperature, and airborne contaminant concentration are in good agreement with
      the corresponding experimental data obtained from an environmental chamber.
      PRACTICAL IMPLICATIONS: This paper presents a simplified method for description
      of complex diffusers in computational fluid dynamics simulation of displacement
      ventilation at high computational efficiency. It may be used to assist the design
      and analysis of air distribution for displacement ventilation as well as other
      types of ventilation with complex diffusers.

PMID- 19383042
TI  - Timely reviews on stem cells for enhancing recovery after stroke as well as an
      important review in cerebus venous thrombosis add to the spectrum.

PMID- 19383043
TI  - Autoregulation in the vertebrobasilar system using transcranial Doppler and CO2
      inhalation.

PMID- 19383044
TI  - Alteplase beyond three hours in ischemic stroke: do we know enough?

PMID- 19383045
TI  - European guidelines on cardiovascular disease prevention.

PMID- 19383046
TI  - Systematic review of process indicators: including early rehabilitation
      interventions used to measure quality of acute stroke care.
AB  - BACKGROUND: Stroke is a leading cause of disease burden. The quality of care
      provided in hospitals can affect outcome. Therefore, examining adherence to
      clinically important processes of care can help improve care delivery and patient
      outcomes. However, knowing which process indicators to measure is essential. AIM:
      Systematically review process indicators used to evaluate acute stroke services,
      including early rehabilitation interventions, and assess whether published
      indicators conform to clinical guidelines. METHODS: Publications (1985-2006) were
      identified by systematically searching databases (e.g. Medline and Cochrane
      Library), and the internet using free text terms: 'stroke unit', 'process',
      'quality', 'mobilisation', 'acute', and 'early rehabilitation'. Publications
      describing process indicators relating to the first 2 weeks of in-patient stroke
      care were included. Process indicators were categorised according to six clinical
      process domains covering the acute stroke admission. Commonly cited indicators
      (>or=6 publications) were then mapped to the 2003 Australian clinical guidelines.
      RESULTS: Sixty potential studies were found from title and abstract. Following
      full text review, 32 publications were retained. Of the 161 process indicators
      identified, 43 were commonly cited. Seventy-nine per cent of commonly cited
      indicators were found in the guidelines. The level of evidence underpinning each
      indicator ranged from low 'expert opinion' (59%), to high, 'level 1' (12%)
      evidence. Indicators related to rehabilitation were rare. CONCLUSION: Many acute
      stroke process indicators have been published. However, a quarter did not align
      with current clinical guidelines. Developing an 'ideal set' of process indicators
      to reflect the evidence base seems sensible and should include rehabilitation
      interventions.

PMID- 19383047
TI  - Long-term prognosis of Chinese patients with a lacunar infarct associated with
      small vessel disease: a five-year longitudinal study.
AB  - RATIONALE: Lacunar infarct associated with small vessel disease is a common
      stroke subtype in China and has a favorable short-term prognosis. Data on its
      long-term prognosis among Chinese patients are lacking. AIMS: We aimed to study
      its long-term prognosis and predictors for poor outcomes. DESIGN: We followed up
      to 75 consecutive Chinese stroke patients who had a lacunar infarct for a period
      of 5 years. Clinical outcomes with respect to mortality and recurrent stroke were
      noted. We evaluated baseline clinical and imaging predictors for such outcomes
      using the Cox regression analysis. STUDY OUTCOMES: Sixteen (21.3%) patients died
      and 12 (16%) patients had recurrent stroke during follow-up. Twenty-one (28%)
      patients had combined events of either death and/or recurrent stroke. Univariate
      Cox regression analysis showed that age, literacy, National Institute of Health
      Stroke Scale, incident stroke/transient ischemic attack, and white matter lesion
      volume predicted survival, while, age, National Institute of Health Stroke Scale,
      systolic blood pressure, hyperhomocysteinemia, silent lacunes, microbleeds, and
      white matter lesion volume predicted recurrent stroke. Multivariate Cox
      regression analysis showed that National Institute of Health Stroke Scale (HR
      1.25, 95% CI 1.05-1.48) and white matter lesion volume (HR 1.46, 95% CI 1.11
      1.92) predicted combined events of mortality and/or recurrent stroke after age
      adjustment. CONCLUSION: Approximately one in four patients either died and/or had
      recurrent stroke within 5 years after a lacunar infarct. Age, stroke severity,
      and volume of white matter lesion predict a poor long-term prognosis.

PMID- 19383048
TI  - Does multidisciplinary stroke care improve outcome in a secondary-level hospital
      in South Africa?
AB  - BACKGROUND AND PURPOSE: The improved outcome (survival and function) of stroke
      patients admitted to multidisciplinary stroke units (SU) in developed countries
      has not been replicated in developing countries in sub-Saharan Africa. This study
      documents the outcome of patients admitted to the first multidisciplinary SU
      opened at a secondary hospital in Cape Town, South Africa. METHODS: Patient
      outcomes including in-hospital mortality, resource utilization (length of
      hospital stay, CT brain scans performed, and tertiary hospital referral), and
      access to inpatient rehabilitation were recorded for all patients admitted to the
      hospital for 3 months before initiating multidisciplinary stroke care and for 3
      months after implementing multidisciplinary stroke care. RESULTS: One hundred and
      ninety-five patients were studied; 101 of these were managed in the SU. Inpatient
      mortality decreased from 33% to 16% after initiating multidisciplinary stroke
      care (P=0.005). The length of hospital stay increased from a mean (SD, 95% CI) of
      5.1 (6.5, 3.8-6.4) days to 6.8 (4.5, 5.9-7.6) days (P=0.01). Referral to
      inpatient rehabilitation increased from 5% to 19% (P=0.04) for those who survived
      to discharge. The number of CT brain scans performed and the number of referrals
      to the tertiary academic hospital did not increase significantly. CONCLUSIONS:
      Multidisciplinary stroke care was successfully implemented in a resource
      constrained secondary-level hospital in South Africa and despite the limitations
      of the study, the significant reduction in inpatient mortality and increase in
      referral for inpatient rehabilitation would suggest an improvement in stroke
      care. Resource utilization in terms of length of hospital stay increased by a
      mean of 2 days but the number of CT brain scans performed and referral to a
      tertiary hospital did not increase significantly.

PMID- 19383049
TI  - Extending the time window for stroke treatment: advanced brain imaging +/- bat
      saliva.

PMID- 19383050
TI  - Rapid advanced neuroimaging assessment in acute stroke.

PMID- 19383051
TI  - Stem cells for enhancing recovery after stroke: a review.
AB  - The potential application for stem cell therapy is vast, and development for use
      in ischaemic stroke is still in its infancy. Access to stem cells for research is
      contentious; however, stem cells are obtainable from both animal and human.
      Despite a limited understanding of their mechanisms of action, clinical trials
      assessing stem cells in human stroke have been performed. Trials are also
      underway evaluating haematopoietic precursors mobilised with granulocyte-colony
      stimulating factor, an approach offering an autologous means of administrating
      stem cells for therapeutic purposes. This review summarises current knowledge in
      regard to stem cells and their potential for helping improve recovery after
      stroke.

PMID- 19383052
TI  - Cerebral venous sinus thrombosis risk factors.
AB  - Cerebral venous sinus thrombosis is an uncommon disease marked by clotting of
      blood in cerebral venous, or dural sinuses, and, in rare cases, cortical veins.
      It is a rare but potentially fatal cause of acute neurological deterioration
      previously related to otomastoid, orbit, and central face cutaneous infections.
      After the advent of antibiotics, it is more often related to neoplasm, pregnancy,
      puerperium, systemic diseases, dehydration, intracranial tumors, oral
      contraceptives, and coagulopathies are the most common causes, but in 30% of
      cases no underlying etiology can be identified. It has been found in association
      with fibrous thyroiditis, jugular thrombosis after catheterization, or idiopathic
      jugular vein stenosis. Other factors include surgery, head trauma, arterio-venous
      malformations, infection, paraneoplastic, and autoimmune disease. This article
      presents a comprehensive review of cerebral venous sinus thrombosis etiologies.

PMID- 19383053
TI  - Stroke nursing in Scotland.

PMID- 19383054
TI  - WSO President's award for services to stroke.

PMID- 19383055
TI  - WSO Leadership in Stroke Medicine Award Lecture Vienna, September 26, 2008:
      functional imaging correlates to disturbance and recovery of language function.
AB  - Disturbance of neurologic function in disorders of the central nervous system is
      expressed as an altered activation pattern in functional networks used by
      specific tasks and can be studied by functional imaging modalities, e.g.,
      positron emission tomography and functional magnetic resonance imaging. Language,
      a complex brain function, is based on the interplay of a distributed network in
      which partial functions are executed in various centers, the primary language
      areas. These areas are hierarchically organized and activated according to the
      complexity of the specific language task. The specialization of different centers
      and the lateralization of integrative functions into the dominant (usually left)
      hemisphere are achieved by collateral and transcallosal inhibition of secondary
      language areas that are not used normally for performance of a specific language
      task. Changes in the interaction within the functional network of language are
      important for the recovery from aphasia after stroke. In particular, studies of
      changes in the activation patterns during speech tasks have demonstrated that
      patients with favorable recovery predominantly activate structures in the
      ipsilateral hemisphere, but some activation was also seen in the right
      hemisphere. Increased activation within the right hemisphere may be a marker of
      failed or faulty recovery attempts in the sense of maladaptive plasticity or the
      breakdown of normal interhemispheric control within the distributed neural
      network. The role of activation in the right hemisphere for residual language
      performance can be investigated by combining repetitive transcranial magnetic
      stimulation (rTMS) with functional imaging [e.g., positron emission tomography
      (PET)]. These studies suggested a less effective compensatory potential of right
      sided network areas. Overactivation of right language homologues may represent a
      maladaptive strategy by paradoxical functional facilitation as a result of
      decreased transcallosal inhibition attributable to damage of specialized and
      lateralized speech areas. Suppression of this paradoxical activation might
      therefore improve aphasic deficits.

PMID- 19383056
TI  - 'Getting your life back on track after stroke': a Phase II multi-centered, single
      blind, randomized, controlled trial of the Stroke Self-Management Program vs. the
      Stanford Chronic Condition Self-Management Program or standard care in stroke
      survivors.
AB  - BACKGROUND: Self-management is seen as a primary mechanism to support the
      optimization of care for people with chronic diseases such as symptomatic
      vascular disease. There are no established and evidence-based stroke-specific
      chronic disease self-management programs. Our aim is to evaluate whether a stroke
      specific program is safe and feasible as part of a Phase II randomized-controlled
      clinical trial. METHODS: Stroke survivors are recruited from a variety of sources
      including: hospital stroke services, local paper advertisements, Stroke South
      Australia newsletter (volunteer peer support organization), Divisions of General
      Practice, and community service providers across Adelaide, South Australia.
      Subjects are invited to participate in a multi-center, single-blind, randomized,
      controlled trial. Eligible participants are randomized to either; * standard
      care, * standard care plus a six week generic chronic condition self-management
      group education program, or, * standard care plus an eight week stroke specific
      self-management education group program. Interventions are conducted after
      discharge from hospital. Participants are assessed at baseline, immediate post
      intervention and six months. STUDY OUTCOMES: The primary outcome measures
      determine study feasibility and safety, measuring, recruitment, participation,
      compliance and adverse events. Secondary outcomes include: * positive and active
      engagement in life measured by the Health Education Impact Questionnaire, *
      improvements in quality of life measured by the Assessment of Quality of Life
      instrument, * improvements in mood measured by the Irritability, Depression and
      Anxiety Scale, * health resource utilization measured by a participant held diary
      and safety. CONCLUSION: The results of this study will determine whether a
      definitive Phase III efficacy trial is justified.

PMID- 19383057
TI  - Patients with acute myocardial infarction using ambulance or private transport to
      reach definitive care: which mode is quicker?
AB  - BACKGROUND: One of the main reasons cited by patients with acute myocardial
      infarction (AMI) for not using an ambulance was quickness of private transport.
      AIMS: To examine differences in transport times for patients with AMI who used
      ambulance compared with patients who used private transportation to reach
      definitive care in Beijing. METHODS: Data were prospectively collected from the
      498 patients with ST-elevation myocardial infarction admitted within 12 h of
      symptom onset to 19 hospitals in Beijing between 1 November 2005 and 31 December
      2006. Elapsed time to definitive care was examined through the use of (i)
      decision to seek care to hospital arrival (private transport group) versus
      emergency medical service (EMS) arrival on scene (ambulance transport group),
      (ii) decision to seek care to hospital arrival, (iii) decision to seek care to
      reperfusion therapy and (iv) symptom onset to reperfusion therapy for both
      groups. RESULTS: Private transportation resulted in faster hospital arrival than
      using ambulance (median, 35 vs 50 min, P < 0.001). However, if one considers EMS
      treatment to be initial definitive care, using ambulance resulted in much quicker
      care than patients using private transportation to the hospital (median, 15 vs 35
      min, P < 0.001). In addition, using ambulance resulted in shorter decision-to
      balloon (173 vs 193 min, P = 0.049) and symptom onset-to-balloon (medians, 223 vs
      300 min, P < 0.001) times compared with patients using private transportation.
      CONCLUSION: Although private transportation results in a faster trip to the
      hospital, quicker definitive care is obtained with the use of ambulance.

PMID- 19383058
TI  - Cardio-selective and non-selective beta-blockers in chronic obstructive pulmonary
      disease: effects on bronchodilator response and exercise.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have
      co-existing cardiovascular disease and may require beta-blocker treatment. There
      are limited data on the effects of beta-blockers on the response to inhaled beta2
      agonists and exercise capacity in patients with COPD. OBJECTIVE: To determine the
      effects of different doses of cardio-selective and non-selective beta-blockers on
      the acute bronchodilator response to beta-agonists in COPD, and to assess their
      effects on exercise capacity. METHODS: A double-blind, randomized, three-way
      cross-over (metoprolol 95 mg, propranolol 80 mg, placebo) study with a final open
      label high-dose arm (metoprolol 190 mg). After 1 week of each treatment, the
      bronchodilator response to salbutamol was measured after first inducing
      bronchoconstriction using methacholine. Exercise capacity was assessed using the
      incremental shuttle walk test. RESULTS: Eleven patients with moderate COPD were
      recruited. Treatments were well-tolerated although two did not participate in the
      high-dose metoprolol phase. The area under the salbutamol-response curve was
      lower after propranolol compared with placebo (P=0.0006). The area under the
      curve also tended to be lower after high-dose metoprolol (P=0.076). The per cent
      recovery of the methacholine-induced fall was also lower after high-dose
      metoprolol (P=0.0018). Low-dose metoprolol did not alter the bronchodilator
      response. Oxygen saturation at peak exercise was lower with all beta-blocker
      treatments (P=0.046). CONCLUSION: Non-selective beta-blockers and high doses of
      cardio-selective beta-blockers may inhibit the bronchodilator response to beta2
      agonists in patients with COPD. Beta-blockers were also associated with lower
      oxygen saturation during exercise. The clinical significance of these adverse
      effects is uncertain in view of the benefits of beta-blocker treatment for
      cardiovascular disease.

PMID- 19383059
TI  - Do medical courses adequately prepare interns for safe and effective prescribing
      in New South Wales public hospitals?
AB  - AIMS: To assess ability of interns immediately before starting clinical practice
      in New South Wales (NSW) teaching hospitals to prescribe medications safely and
      appropriately and to describe their impressions of the adequacy of their clinical
      pharmacology training in medical school. METHODS: A cross-sectional study was
      performed on all interns (n= 191) who attended intern orientation programmes at
      four NSW hospitals in January 2008. A clinical case scenario that tested
      prescribing ability and a survey investigating impressions of clinical
      pharmacology training in medical school were administered to the interns in exam
      format. Outcome measures were: (i) ability to prescribe medications safely and
      appropriately for the clinical case scenario and (ii) interns' impressions of
      their training in clinical pharmacology at medical school. RESULTS: No intern
      completed all prescribing tasks correctly. No intern charted the patient's usual
      medications on admission completely correctly, only six wrote an accurate
      discharge medication list, and none wrote both an accurate discharge medication
      list and a legal Schedule 8 discharge script. None of the respondents strongly
      agreed that they felt adequately trained to prescribe medications in their intern
      year and 84% would have liked to have more training in pharmacology as medical
      students. CONCLUSIONS: Interns about to commence clinical practice in NSW
      teaching hospitals demonstrated significant deficits in prescribing of regular
      medications, initiation of new therapies, prescribing of discharge medications,
      and particularly prescribing of Schedule 8 medications. Most interns recognized
      these deficits and would have liked more clinical pharmacology training at
      medical school.

PMID- 19383060
TI  - Challenges in secondary stroke prevention: prevalence of multiple metabolic risk
      factors, including abnormal glycaemia, in ischaemic stroke and transient
      ischaemic attack.
AB  - BACKGROUND: Secondary prevention of ischaemic stroke (IS) and transient ischaemic
      attack (TIA) mandates identification and treatment of multiple metabolic risk
      factors. The aim was to determine the prevalence of abnormal glycaemia,
      hypertension and dyslipidaemia in patients presenting to an Acute Stroke Unit of
      a tertiary referral teaching hospital with IS or TIA. METHODS: We reviewed the
      clinical characteristics of consecutive patients presenting with symptoms of
      acute stroke or TIA between 1 February 2006 and 30 June 2007 to determine the
      prevalence of diabetes, impaired fasting glucose (IFG), post-stroke dysglycaemia
      (PSD), hypertension and dyslipidaemia. RESULTS: Mean age +/- SD of the 224
      patients (84 female) was 71 +/- 15 years. Seventy per cent (n= 157) of patients
      presented with IS and 30% (n= 67) with TIA. Of the cohort, 15% (n= 33) had
      previously diagnosed diabetes, 10% (n= 22) were diagnosed with diabetes during
      admission and 19% (n= 42) had IFG diagnosed during admission. A further 4% (n= 9)
      were classified as having PSD. Sixty-two per cent (n= 139) of patients had
      previously diagnosed hypertension; another 7% (n= 15) were diagnosed during
      admission. Eighty-eight per cent (n= 197) of patients had dyslipidaemia. Thirty
      per cent had all three risk factors concurrently. CONCLUSION: Abnormal glycaemia
      was present in almost half the patients presenting with IS/TIA, with the majority
      of cases undiagnosed. One-third of patients had abnormal glycaemia, hypertension
      and dyslipidaemia concurrently. Patients presenting with stroke should be
      routinely screened for abnormal glycaemia in concert with other vascular risk
      factors.

PMID- 19383061
TI  - Could exercise be a new strategy to revert some patients with atrial
      fibrillation?
AB  - BACKGROUND: This study is the result of the anecdotal observation that a number
      of patients with atrial fibrillation (AF) had noted reversion to sinus rhythm
      (SR) with exercise.We aimed to evaluate the potential role of exercise stress
      test (EST) for the reversion of AF. METHODS: Patients with AF who were scheduled
      to undergo electrical cardioversion (DCR) underwent EST using a modified Bruce
      protocol. RESULTS: Eighteen patients (16 male); aged 36-74 years (mean 58 years)
      were studied. Five patients (27.7%) had successful reversion with exercise (group
      1). Thirteen patients remained in AF (group 2). No patient who failed to revert
      with exercise did so spontaneously before DCR 3 h to 7 months later (median 20
      days). Comparison between group 1 and group 2 did not reveal any significant
      difference CONCLUSION: This small preliminary study suggests that in some
      patients it may be possible to revert AF to SR with exercise and avoid DCR and
      concomitant general anaesthesia. The authors suggest that a larger multicentre
      randomized trial is warranted to confirm or refute these initial results and if
      correct identify those who might benefit.

PMID- 19383062
TI  - A survey of medical staff attitudes to an antibiotic approval and stewardship
      programme.
AB  - BACKGROUND: Antibiotic stewardship programmes (ASPs) are advocated to ensure
      appropriate antimicrobial use; with short-term evidence they may improve
      outcomes, limit adverse effects, encourage cost-effectiveness and reduce
      antibiotic resistance. At Concord Hospital, a 450-bed acute care hospital, we
      have used a telephone-based ASP for 15 years. There may be differences in
      attitudes to the ASP by prescribers, which may influence its long-term efficacy.
      METHOD: A 40-item self-administered questionnaire was sent to 190 junior and 250
      specialist medical staff. We aimed to elicit medical staff attitudes to the ASP's
      utility, educational value, effect on patient care and ease of use. RESULTS: One
      hundred and sixty-four completed questionnaires were returned. Most (82%, 95%
      confidence interval (95%CI) 75-87%) clinicians had used the ASP, 98% of whom
      believed it to be a reasonable system. Most staff (85%, 95%CI 79-90%) believed
      that seeking approval made teams think carefully about antibiotic choice, agreed
      it provided helpful advice (91%, 95%CI 85-95%) and that the approval system
      provided useful advice and was educational (88%, 95%CI 81-92%). The ASP was felt
      time-consuming and detracting from clinical duties by 33% (95%CI 26-41%), while
      10% (95%CI 5.8-15.7%) believed it undervalued intuition and experience. Few (19%,
      95%CI 13-25%, P < 0.0001) clinicians believed it infringed their autonomy. The
      advice given through the ASP was believed by most (89%, 95%CI 81-92%) to improve
      patient outcomes. CONCLUSION: The ASP was surprisingly well supported by all
      levels of staff, and reinforced the benefits of maintaining an ASP policy.

PMID- 19383063
TI  - Association between cholesterols, homocysteine and silent brain infarcts.
AB  - BACKGROUND: The aim of this study was to assess the relationship between total
      plasma homocysteine, cholesterol levels, vitamin B(12), folate, thyroid hormones,
      urea, ferritin, uric acid, C-reactive protein, cardiovascular risk factors and
      silent brain infarct (SBI) in patients without any neurological disorder. Whether
      the factors of interest were associated with SBI is investigated. METHODS: One
      hundred and forty-two subjects with a mean age of 52.1 +/- 13.1 years (21-87
      years) without any history of stroke, transient ischaemic attack and neurological
      abnormality were enrolled in this cross-sectional study. The subjects underwent
      brain magnetic resonance imaging and blood chemistry determinations. Student's t
      test was used to compare differences in means of laboratory results between the
      groups with and without SBI. The chi(2)-test was used for categorized variables.
      Multiple logistic regression analysis was used to determine the independent
      predictors of SBI. RESULTS: The group comprised 56 men and 86 women. SBI were
      found in 40 patients (28%). The low-density lipoprotein levels were significantly
      higher in the infarct group (P = 0.019), homocysteine concentrations were
      significantly higher in the men-infarct group (P = 0,029) and total cholesterol
      levels were significantly higher in the women-infarct group than the women non
      infarct group (P = 0.006). CONCLUSION: Serum low-density lipoprotein, total
      cholesterol and homocysteine levels were associated with SBI.

PMID- 19383064
TI  - Recombinant human thyroid-stimulating hormone (Thyrogen) in thyroid cancer follow
      up: experience at a single institution.
AB  - BACKGROUND: Recombinant human thyroid-stimulating hormone (Thyrogen; Genzyme
      Corporation, Cambridge, MA, USA) (rhTSH)-stimulated serum thyroglobulin (Tg)
      (stim-Tg) and (131)I whole-body scanning (WBS) have been reported to allow follow
      up of patients with thyroid cancer without the symptoms of thyroxine withdrawal
      and with equivalent diagnostic information to that obtained after thyroxine
      withdrawal. The aim of the study was to report results of rhTSH use at the Alfred
      Hospital, Melbourne, from 1999 to 2006 and in particular to examine the
      significance of detectable serum Tg after rhTSH in relation to thyroid cancer
      staging and to compare the sensitivity of rhTSH-stimulated serum Tg to whole-body
      (131)I scanning (WBS) in the detection of residual and recurrent thyroid cancer.
      METHODS: The study was a retrospective chart review. RESULTS: In 90 patients,
      rhTSH was used for 96 diagnostic episodes and 18 doses of rhTSH were used to
      facilitate treatment with (131)I. In stages I and II cancer (n = 42), of three
      patients with stim-Tg 1-2 microg/L, none had identifiable disease, and the three
      patients who had stim-Tg >2 microg/L did not experience recurrent disease during
      follow up. In contrast, in stages III and IV cancer (n = 43) 2 of 5 with stim-Tg
      1-2 microg/L had identifiable disease and 7 of 10 with stim-Tg >2 microg/L had
      identifiable disease. In Tg-positive, WBS-negative disease, further imaging
      identified persistent/recurrent disease. CONCLUSION: rhTSH was effective and safe
      in the management of thyroid cancer follow up for diagnosis of
      persistent/recurrent cancer and to enable (131)I treatment. In no case did rhTSH
      stimulated WBS identify the presence of disease not also identified by raised
      basal Tg or stim-Tg. Therefore, in low risk cancer WBS may be omitted.

PMID- 19383065
TI  - Perceptions and attitudes of rehabilitation medicine physicians on complementary
      and alternative medicine in Australia.
AB  - BACKGROUND: The growing demand for complementary and alternative medicine (CAM)
      is undeniable. We report a first study about the attitudes and behaviour of
      Australian rehabilitation physicians to CAM. METHODS: A prospective cross
      sectional survey was undertaken to document the prevalence of, knowledge about
      and referrals to CAM therapies and their perceived effectiveness, by a sample of
      Australian rehabilitation physicians. RESULTS: Thirty-six out of 94 actively
      practising rehabilitation physicians from the Australasian Faculty of
      Rehabilitation Medicine, the Royal Australasian College of Physicians, replied to
      the survey, a response rate of 38%, and 85% reported familiarity with CAM, the
      most familiar therapies being acupuncture (80%), yoga (74%) and Tai-Chi (72%).
      CAM referral was reported in 84%, 38% personally used CAM, 94% of patients
      enquired about CAM therapies, 32% of respondents routinely enquired about CAM
      use. Age, sex and year of Fellowship were not associated with familiarity,
      personal use or frequency of patient enquiry about CAM. Those who reported to be
      very familiar with CAM were more likely to routinely enquire about CAM use (P =
      0.028) and be more confident in prescribing certain CAM therapies (P < 0.05).
      CONCLUSION: Australian rehabilitation physicians report similar CAM referral
      rates to Canadian physiatrists and Australian general practitioners. The most
      commonly prescribed therapies were acupuncture, yoga and Tai-Chi. Almost all
      patients use CAM therapies, but only a minority of rehabilitation physicians
      enquires about CAM use on a regular basis. The latter may avoid potentially
      harmful drug interactions, as well as improve the quality of the physician
      patient relationship.

PMID- 19383066
TI  - Evaluation of the impact of breast cancer screening in South Australia.
AB  - BACKGROUND: In 1989 BreastScreen SA started screening for breast cancer in South
      Australia. METHODS: The programme concentrated on women between the ages of 50
      and 69, using a 24-month screening interval and a joint method of mammography,
      clinical examination and self-detection. RESULTS: This paper is a summary of our
      efforts to provide an assessment of the impact of the screening programme in
      terms of additional survival time past the age of first detection of the disease.
      DISCUSSION: The concept of benchmarks is introduced, and the survival advantages
      for screened women is measured from these benchmarks. CONCLUSION: The women in
      the BreastScreen SA service, who had primary breast tumours, had an estimated
      additional survival advantage of 2.6 years. Some statistical modelling allowed us
      to extrapolate to other screening designs.

PMID- 19383067
TI  - Patient awareness and concern regarding pharmaceutical manufacturer interactions
      with doctors.
AB  - BACKGROUND: The objective of the study was to determine the general public's
      level of awareness of and degree of concern about the interactions between
      pharmaceutical manufacturers and doctors in Melbourne. This Internet was survey
      administered using Survey Monkey. METHODS: The participants in the study were
      employees of The Age Newspaper in Melbourne (n = 1524). Participants' self
      reported levels of awareness and concern regarding pharmaceutical
      representatives' interactions with doctors and the resulting effect on the
      quality of care they receive were observed. RESULTS: One hundred and thirty-four
      participants completed the questionnaire between 18 January and 8 February 2007.
      This was a response rate of 8.8%, and 40% reported a 'high level' of awareness of
      pharmaceutical marketing, whereas 59% reported believing that marketing
      influenced the prescribing behaviour of their doctors. Participants who reported
      that information provided by the pharmaceutical industry is inaccurate were
      significantly more likely to prefer a doctor who did not engage with
      pharmaceutical marketing (H(2) = 0.19, P < 0.05). There was a significant
      difference in perceived trustworthiness between academic sources of information
      and marketing based sources of information (T = 0.000, P < 0.05). The level of
      perceived trustworthiness of pharmaceutical marketing was significantly related
      to whether people wanted to be kept informed about pharmaceutical marketing
      activities (H(2) = 0.004, P < 0.05). Forty-eight per cent of respondents wanted
      to be informed about pharmaceutical marketing; 46.2% of these people would like
      this to be through disclosure in the form of an accredited identification system.
      If given a choice, 38.8% of respondents would choose a doctor who did not see
      pharmaceutical representatives over one that did. CONCLUSION: A significant
      proportion of the sample surveyed was aware of pharmaceutical marketing, believed
      that it influenced prescribing practices and it was less trustworthy than
      academic sources of information, would like to be kept informed about industry
      interactions with their doctor and would prefer to see a doctor who did not
      receive visits from pharmaceutical marketing representatives.

PMID- 19383068
TI  - Rare cause of dyspnoea.
AB  - Although primary amyloidosis is the most common systemic form of amyloidosis, its
      diagnosis remains notoriously difficult. Unless included in the differential
      diagnosis, the condition may be missed as a cause of severe and ultimately fatal
      clinical syndromes. We describe two patients with primary amyloidosis who
      presented with dyspnoea/orthopnoea and oedema due to cardiac and renal
      involvement. Both had a fatal outcome.

PMID- 19383069
TI  - Barriers to the implementation of evidence in osteoporosis treatment in hip
      fracture.
AB  - An audit at a private tertiary hospital showed low rates of assessment and
      treatment of osteoporosis in minimal trauma patients of hip fracture. A survey
      sent to all doctors involved in hip fracture care to establish medical beliefs
      about effective management of osteoporosis in minimal trauma hip fracture
      patients showed a lack of ownership for investigation and beliefs influencing
      treatment choices. Understanding the barriers to the translation of evidence into
      practice is vital to improve patient care.

PMID- 19383070
TI  - Pleuropulmonary paragonimiasis.

PMID- 19383071
TI  - Dural arteriovenous malformation.

PMID- 19383073
TI  - Anicteric cholestasis: an unusual presentation of myotonic dystrophy.

PMID- 19383072
TI  - Brain metastases in hormone refractory prostate cancer: a changing natural
      history?

PMID- 19383074
TI  - Severe hypercalcaemia in sarcoidosis with musculoskeletal involvement.

PMID- 19383075
TI  - Concerns about efficacy and safety of statins in the prevention of stroke.

PMID- 19383076
TI  - Inbreeding avoidance under different null models of random mating in the great
      tit.
AB  - 1. In populations where inbreeding causes a substantial decrease in fitness,
      selection is expected to favour the evolution of inbreeding avoidance behaviours.
      Elsewhere we have documented substantial inbreeding depression and the importance
      of dispersal in avoiding inbreeding in a long-term population study of the great
      tit Parus major in Wytham (UK). In this study, we ask whether individuals from
      this population actively avoid mating with kin. 2. We generated four contrasting
      models of random mate choice that assumed varying levels of mate availability in
      each year of the data set. This allowed us to compare observed and simulated
      distributions and frequencies of inbreeding coefficients from 41 years of
      breeding data. 3. We found no evidence that birds avoid mating with related
      partners. Our results show that birds breed more often with relatives than
      expected under null models of mate choice that lack population structure, but not
      when compared to scenarios where birds were mated with their nearest neighbours.
      Pedigree-derived F(IS) values were positive for all scenarios of random mating,
      confirming the lack of inbreeding avoidance in this population. 4. These results
      imply the existence of spatial genetic structure where related individuals occur
      closer together than nonrelated individuals while breeding, and suggest that the
      relatedness between breeding individuals of the opposite sex decreases with
      distance. Thus, while dispersal from the natal site decreases the number of
      relatives around an individual, it does not completely homogenize genetic
      structure. 5. We show that brother-sister pairs are observed more often than
      under any scenario of random mating, suggesting that not only birds do not avoid
      mating with kin, but also that the apparently maladaptive choice of mating with a
      sibling is made more often than expected. 6. Our results provide no evidence to
      suggest that individuals actively avoid kin. In fact, some types of inbreeding
      occur more often than expected, despite the substantial fitness costs. The
      observed lack of inbreeding avoidance is in agreement with other studies of non
      cooperatively breeding passerine birds, although the higher than expected
      frequency of sibling mating remains a puzzling result.

PMID- 19383077
TI  - Endoscopic retrograde pancreatography in pancreatic trauma: need to break the
      mental barrier.
AB  - Pancreatic injury has a high morbidity and mortality. The integrity of the main
      pancreatic duct is the most important determinant of prognosis. Serum amylase,
      peritoneal lavage and computed tomography of the abdomen can assist with
      diagnosis but endoscopic retrograde pancreatography (ERP) is the most accurate
      investigation for diagnosing the site and extent of ductal disruption. However,
      it is invasive and can be associated with significant complications. Magnetic
      resonance cholangiopancreatography (MRCP) and secretin-enhanced MRCP probably
      parallel ERP in delineating pancreatic ductal injuries. They can also delineate
      the duct upstream to complete disruption, an area not visualized on ERP. In
      relation to therapy, endoscopic transpapillary drainage has been successfully
      used to heal duct disruptions in the early phase of pancreatic trauma and, in the
      delayed phase, to treat the complications of pancreatic duct injuries such as
      pseudocysts and pancreatic fistulae. Transpapillary drainage is especially
      effective in patients who have partial pancreatic duct disruption that can be
      bridged. Endoscopic transmural drainage has also been successfully used to treat
      post-traumatic pancreatic pseudocysts. Further large, prospective and randomized
      studies are required to adjudge the efficacy and long-term safety of pancreatic
      duct drainage in the treatment of post-traumatic pancreatic duct injuries.

PMID- 19383078
TI  - Thyroid dysfunction in patients with chronic hepatitis C: virus- or therapy
      related?
AB  - BACKGROUND AND AIMS: Thyroid dysfunction (TD) represents an extrahepatic
      manifestation of chronic hepatitis C (CHC). Moreover, the currently approved
      treatment of CHC is often associated with TD. However, it remains debatable if TD
      is mainly virus- or treatment-related. The aim of this study was to assess the
      incidence and features of TD, and to identify its predictors in treated and
      untreated CHC patients. METHODS: Ninety-four patients with CHC and normal thyroid
      function were evaluated long-term for TD: 33 were untreated (control group) and
      61 were treated with pegylated interferon alpha (PEG-IFN-alpha) plus ribavirin
      (treatment group). Mean follow up was 80.1 and 39.4 months, respectively.
      RESULTS: All patients in the control group remained euthyroid, while 13 treated
      patients (21.3%) developed TD (P < 0.001). Eleven of these were diagnosed with
      hypothyroidism and two with hyperthyroidism, which then converted to
      hypothyroidism. In the majority of cases (9/13, 69.2%) TD did not reverse after
      treatment discontinuation and required hormone replacement therapy. Pretreatment
      virological parameters did not predict TD, according to multiple logistic
      regression analysis. TD was not associated with total dose of PEG-IFN-alpha or
      ribavirin, viral kinetics or with virological outcome, but it was linked to
      development of other therapy-related autoimmune disorders (odds ratio, 8.29).
      CONCLUSION: Antiviral therapy of CHC possibly induces de novo or exacerbates pre
      existing silent TD. TD does not seem to correlate with any pretreatment
      virological parameter; it is probably not related to dose or treatment duration,
      nor linked to viral kinetics or virological outcome. The role of chronic
      hepatitis C per se in TD remains to be determined.

PMID- 19383079
TI  - Benefits of endoscopic submucosal dissection according to size and location of
      gastric neoplasm, compared with conventional mucosal resection.
AB  - BACKGROUND AND AIMS: To clarify optimal therapeutic strategies for early gastric
      cancers without vestigial remnant or recurrence, we evaluated the benefits of
      endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD)
      according to tumor size and location. METHODS: From January 2000 to December
      2007, a total of 328 gastric lesions were treated using conventional EMR, while
      572 lesions were treated by ESD. Patients who underwent surgery on the upper
      gastrointestinal tract before EMR or ESD were excluded from the study. We
      compared tumor size, location and rates of complete resection, curative
      resection, postoperative bleeding, perforation and local recurrence between EMR
      and ESD according to tumor situation. RESULTS: Overall local complete resection
      rate (EMR, 64.2%; ESD, 95.1%) and overall curative resection rate (EMR, 59.5%;
      ESD, 82.7%) were significantly higher in ESD than in EMR. No significant
      differences were seen in complication rates between EMR and ESD. Local recurrence
      was detected in 13 lesions (4.0%) of the EMR group during follow up. In contrast,
      no local recurrence was detected in the ESD group. For lesions 5 mm or less in
      diameter, complete resection rate in the EMR group was not significantly inferior
      to that in the ESD group at any location. However, rates were overwhelmingly
      better in the ESD group than in the EMR group for lesions more than 5 mm in
      diameter, regardless of location. CONCLUSION: We concluded that lesions exceeding
      5 mm in diameter should be treated by ESD, although a high resection rate is
      obtained also with EMR for lesions of 5 mm or less in diameter.

PMID- 19383081
TI  - Application of per oral cholangiopancreatoscopy in pancreatobiliary diseases.
AB  - Pancreaticobiliary ductal diseases are largely investigated by indirect imaging
      techniques. Therefore, the pathology of up to 30% of cases remains undetermined.
      Cholangiopancreatoscopy allows direct visualization of ductal abnormalities with
      the ability to sample tissue and deliver a number of endotherapies. The technique
      can be broadly categorized into either two-operator or single-operator systems.
      Both systems provide important diagnostic information in the investigation of
      undetermined biliary or pancreatic strictures, intraductal papillary mucinous
      neoplasia, occult ductal malignant changes in patients with primary sclerosing
      cholangitis and occult intraductal stones in patients with complex biliary stone
      diseases. Therapeutically, cholangiopancreatoscopy-guided endotherapies provide a
      highly effective and safe alternative to surgery for patients with difficult
      extrahepatic and intrahepatic ductal stones that are not amenable to conventional
      endoscopic extraction by endoscopic retrograde cholangiopancreatography. The
      clinical application of cholangiopancreatoscopy, however, will be limited unless
      the technology is further refined to improve its durability, image quality,
      therapeutic capability and technical feasibility.

PMID- 19383080
TI  - Significance of lymphatic invasion and cancer invasion-related proteins on lymph
      node metastasis in gastric cancer.
AB  - BACKGROUND AND AIMS: Cancer invasion and metastasis are critical events for
      patient prognosis; however, the most important step in the whole process of lymph
      node (LN) metastasis in gastric cancer remains obscure. In this study, the
      significance of cancer cell behaviors, such as cell detachment, stromal invasion
      and lymphatic invasion on regional LN metastasis in gastric cancer was
      investigated by comprehensive immunohistochemistry. METHODS: A total of 210 cases
      with gastric cancer were selected. These consisted of 105 cases with regional LN
      metastasis (LN[+] group) and 105 cases without LN metastasis (LN[-] group). Both
      groups exhibited the same depth of invasion. Cancer tissues were subjected to
      immunohistochemistry with antibodies against claudin-3, claudin-4, beta-catenin,
      matrix metalloproteinase (MMP)-1, and MMP-2, as well as endothelial markers of
      lymphatic vessel endothelial hyaluronan receptor-1 and von Willebrand factor for
      the objective discrimination between lymphatics and blood vessels. The expression
      of each protein as well as the histopathological parameters were compared between
      LN(+) and LN(-) groups. RESULTS: Along with lymphatic invasion by cancer cells
      and gross tumor size, MMP-1 expression in cancer cells at the invasive front of
      the primary tumor was a significant, independent predictor of LN metastasis. The
      expression of claudins and beta-catenin was associated with the histopathological
      type of cancer, but not with LN status. CONCLUSION: Among the cancer invasion
      related proteins examined, MMP-1 plays a vital role in LN metastasis of gastric
      cancer. Tumor size, lymphatic invasion and MMP-1 expression level at the invasive
      front were the predictive factors of LN metastasis of gastric cancer.

PMID- 19383082
TI  - Application of surveillance programs for hepatocellular carcinoma in the Asia
      Pacific Region.
AB  - Hepatocellular carcinoma (HCC) is a potential target for cancer surveillance (or
      screening) as it occurs in well-defined, at-risk populations and curative therapy
      is possible only for small tumors. Surveillance has been recommended by regional
      liver societies and is practiced widely, but its benefits are not clearly
      established. Hepatic ultrasonography with or without alpha fetoprotein (AFP)
      performed every 6 months is the preferred program. Surveillance of HCC has been
      well shown to detect small tumors for curative treatment, which may be translated
      to improved patient survival. However, most studies are limited by lead-time
      bias, length bias for early diagnosis of small HCC, different tumor growth rates
      and poor compliance with surveillance. Cost-effectiveness of surveillance
      programs depends on the rate of small HCC detected 'accidentally' (routine
      imaging) in a comparator group, annual incidence of HCC with various etiologies,
      patient age and the availability of liver transplantation. The incremental cost
      effectiveness for 6-monthly AFP and ultrasound has been estimated from
      approximately $US 26,000-74,000/quality adjusted life years (QALY). All cirrhotic
      patients are therefore recommended for HCC surveillance unless the disease is too
      advanced for any curative treatment. As chronic hepatitis B can develop into HCC
      without going through liver cirrhosis, high-risk non-cirrhotic chronic hepatitis
      B patients are also recommended for HCC surveillance. In conclusion, HCC
      surveillance could be effective at reducing disease-specific mortality with
      acceptable cost-effectiveness among selected patient groups, provided it is a
      well-organized program.

PMID- 19383083
TI  - Increased heat-shock protein 90 expression contributes to impaired adaptive
      cytoprotection in the gastric mucosa of portal hypertensive rats.
AB  - BACKGROUND AND AIMS: Portal hypertensive (PHT) gastropathy results in an
      increased susceptibility to damage. Adaptive cytoprotection against ethanol
      induced damage is impaired in the gastric mucosa of rats with portal
      hypertension. Excessive nitric oxide (NO) production occurs in portal
      hypertension and is mediated in part via heat-shock protein (Hsp)90 production.
      The aim of this study was to investigate the relation between adaptive
      cytoprotection after exposure to ethanol and gastric expression of Hsp90 in PHT
      rats. METHODS: Portal hypertension was induced in rats by staged portal vein
      occlusion. Adaptive cytoprotection to 70% ethanol was evaluated by assessing the
      injury index of the gastric mucosa with or without pretreatment with 10% ethanol.
      Expression of Hsp90 mRNA was evaluated by real-time polymerase chain reaction,
      and expression of Hsp90 protein was evaluated by western blotting. The effect of
      Hsp90 inhibition in PHT rats was evaluated by administration of geldanamycin.
      RESULTS: Gastric Hsp90 mRNA expression in PHT rats was significantly less than
      that in sham-operated (SO) controls. However, after 10% ethanol pretreatment,
      Hsp90 mRNA expression was significantly greater in PHT rats than in SO controls.
      In PHT rats, gastric Hsp90 protein expression after 10% ethanol pretreatment was
      significantly greater than that without the pretreatment. However, the
      pretreatment had no effect on the injury index compared to SO rats.
      Administration of geldanamycin prior to 10% ethanol pretreatment significantly
      decreased the injury index in response to 70% ethanol in the PHT rats.
      CONCLUSIONS: These results show that 10% ethanol pretreatment markedly increases
      gastric Hsp90 expression in PHT rats. Excessive production of Hsp90 may
      contribute impaired adaptive cytoprotection.

PMID- 19383084
TI  - Enhanced antinociceptive response to intracerebroventricular kyotorphin in Pept2
      null mice.
AB  - L-Kyotorphin (L-KTP), an endogenous analgesic neuropeptide, is a substrate for
      aminopeptidases and a proton-coupled oligopeptide transporter, PEPT2. This study
      examined the CSF efflux, antinociceptive response, and hydrolysis kinetics in
      brain of L-KTP and its synthetic diastereomer D-kyotorphin (D-KTP) in wild-type
      and Pept2 null mice. CSF clearance of L-KTP was slower in Pept2 null mice than in
      wild-type animals, and this difference was reflected in greater L-KTP-induced
      analgesia in Pept2 null mice. Moreover, dose-response analyses showed that the
      ED50 of L-KTP in Pept2-deficient animals was one-fifth of the value observed in
      Pept2-competent animals (4 vs. 21 nmol for null vs. wild-type mice,
      respectively). In contrast, the ED50 of D-KTP was very similar between the two
      genotypes (9-10 nmol). Likewise, there was little difference between genotypes in
      slope factor or baseline effects of L-KTP and D-KTP. The enhanced antinociceptive
      response to L-KTP in Pept2 null mice could not be explained by differences in
      neuropeptide degradation as Vmax and Km values did not differ between genotypes.
      Our results demonstrate that PEPT2 can significantly impact the analgesic
      response to an endogenous neuropeptide by altering CSF (and presumably brain
      interstitial fluid) concentrations and that it may influence the disposition and
      response to exogenous peptide/mimetic substrates.

PMID- 19383085
TI  - The brain-specific protein, p42(IP4) (ADAP 1) is localized in mitochondria and
      involved in regulation of mitochondrial Ca2+.
AB  - In brain, p42(IP4) (centaurin-alpha1; recently named ADAP 1, which signifies ADP
      ribosylation factor GTPase activating protein with dual PH domains 1, within the
      large family of Arf-GTPase activating proteins) is mainly expressed in neurons.
      p42(IP4) operates as a dual receptor recognising two second messengers, the
      soluble inositol(1,3,4,5)tetrakisphosphate and the lipid
      phosphatidylinositol(3,4,5)trisphosphate. We show here for the first time that
      p42(IP4) is localized in mitochondria, isolated from rat brain and from cells
      transfected with p42(IP4). In rat brain mitochondria we additionally found
      interaction of p42(IP4) with 2', 3'-cyclic nucleotide 3'-phosphodiesterase and
      alpha-tubulin by pull-down binding assay and by immunoprecipitation. In
      mitochondria from Chinese hamster ovary cells, p42(IP4) is predominantly
      associated with the intermembrane space and the inner membrane. This localization
      of p42(IP4) indicates that p42(IP4) might have a still unknown mitochondrial
      function. We studied whether p42(IP4) is involved in Ca(2+)-induced permeability
      transition pore opening, which is important in mitochondrial events leading to
      programmed cell death. We used mouse neuroblastoma cells as a model for the
      functional studies of p42(IP4) in mitochondria. In mitochondria isolated from
      p42(IP4)-transfected mouse neuroblastoma cells, over-expression of p42(IP4)
      significantly decreased Ca(2+) capacity and lag time for Ca(2+) retention. Thus,
      we suggest that p42(IP4) is involved in the regulation of Ca(2+) transport in
      mitochondria. We propose that p42(IP4) promotes Ca(2+)-induced permeability
      transition pore opening and thus destabilizes mitochondria.

PMID- 19383086
TI  - Prenatal stress alters glutamatergic system responsiveness in adult rat
      prefrontal cortex.
AB  - Exposure to stress during gestation alters brain development resulting in
      permanent alterations that may increase susceptibility to subsequent cognitive or
      neuropsychiatric disorders. In this manuscript we examined the effects of
      prenatal stress on critical determinants of the glutamatergic synapse under basal
      conditions as well as in response to acute stress. The main finding of this work
      is that gestational stress altered the responsiveness of the glutamatergic system
      following a challenge at adulthood. In fact, while in control animals acute swim
      stress enhanced the phosphorylation levels of the NMDA receptor subunits NR
      1(Ser896) and NR-2B(Ser1303) as well as the phosphorylation levels of alpha
      calcium/calmodulin-dependent protein kinase II (Thr286), a crucial sensor of
      calcium fluctuations, prenatal stress prevented or attenuated such activation.
      This dynamic modulation is restricted to prefrontal cortex since no changes were
      observed in the hippocampus, in line with the different maturational profile of
      these brain regions. Changes were also observed in the phosphorylation of the
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate subunit GluR-1(Ser831)
      which, however, relied on the acute stress exposure and were independent of
      gestational stress. These effects point to a unique interference of chronic
      prenatal stress with the responsiveness of specific determinants of the
      glutamatergic synapse at adulthood in a region specific manner. The inability to
      mount an homeostatic glutamatergic response to subsequent stress at adulthood may
      impair the normal responses of the cell to challenging situations.

PMID- 19383087
TI  - Inhibiting astrocytic activation: a novel analgesic mechanism of ketamine at the
      spinal level?
AB  - Although ketamine is widely used as an analgesic agent and has an anti-allodynic
      effect on neuropathic pain, the underlying analgesic mechanisms are not fully
      explained by the modern 'neuronal-based' theories. As emerging studies have
      focused on the critical role of spinal astrocytes in the pathological pain
      states, we have hypothesized that there exist some 'astrocytes-related'
      mechanisms in the analgesic function of ketamine. In the present study, using the
      spinal nerve ligation (SNL) pain model, we investigated the anti-nociceptive
      effects of intraperitoneal or intrathecal ketamine on SNL-induced neuropathic
      pain response, meanwhile, we investigated the astrocytic activation after
      ketamine administration on SNL rats. Behavioral data showed that either
      intraperitoneal or intrathecal ketamine inhibited SNL-induced allodynia, however,
      immunohistochemistry showed that SNL induced astrocytic activation was suppressed
      by intrathecal but not intraperitoneal ketamine. Using quantitative Western blot
      analysis, our report showed that intrathecal ketamine down-regulated glial
      fibrillary acidic protein expression, suggesting inhibition of SNL-induced
      astrocytic activation, which wasn't influenced by intraperitoneal administration.
      We conclude that intraperitoneal ketamine could alleviate SNL-induced neuropathic
      pain via the classical 'neuronal-based' mechanisms, but in addition, 'astrocytes
      related' mechanisms were also important underlying the anti-allodynic effect of
      intrathecal ketamine.

PMID- 19383088
TI  - Morphine withdrawal produces circadian rhythm alterations of clock genes in
      mesolimbic brain areas and peripheral blood mononuclear cells in rats.
AB  - Previous studies have shown that clock genes are expressed in the suprachiasmatic
      nucleus (SCN) of the hypothalamus, other brain regions, and peripheral tissues.
      Various peripheral oscillators can run independently of the SCN. However, no
      published studies have reported changes in the expression of clock genes in the
      rat central nervous system and peripheral blood mononuclear cells (PBMCs) after
      withdrawal from chronic morphine treatment. Rats were administered with morphine
      twice daily at progressively increasing doses for 7 days; spontaneous withdrawal
      signs were recorded 14 h after the last morphine administration. Then, brain and
      blood samples were collected at each of eight time points (every 3 h: ZT 9; ZT
      12; ZT 15; ZT 18; ZT 21; ZT 0; ZT 3; ZT 6) to examine expression of rPER1 and
      rPER2 and rCLOCK. Rats presented obvious morphine withdrawal signs, such as teeth
      chattering, shaking, exploring, ptosis, and weight loss. In morphine-treated
      rats, rPER1 and rPER2 expression in the SCN, basolateral amygdala, and nucleus
      accumbens shell showed robust circadian rhythms that were essentially identical
      to those in control rats. However, robust circadian rhythm in rPER1 expression in
      the ventral tegmental area was completely phase-reversed in morphine-treated
      rats. A blunting of circadian oscillations of rPER1 expression occurred in the
      central amygdala, hippocampus, nucleus accumbens core, and PBMCs and rPER2
      expression occurred in the central amygdala, prefrontal cortex, nucleus accumbens
      core, and PBMCs in morphine-treated rats compared with controls. rCLOCK
      expression in morphine-treated rats showed no rhythmic change, identical to
      control rats. These findings indicate that withdrawal from chronic morphine
      treatment resulted in desynchronization from the SCN rhythm, with blunting of
      rPER1 and rPER2 expression in reward-related neurocircuits and PBMCs.

PMID- 19383090
TI  - The emerging role of epigenetic modifications and chromatin remodeling in spinal
      muscular atrophy.
AB  - As the leading genetic cause for infantile death, Spinal Muscular Atrophy (SMA)
      has been extensively studied since its first description in the early 1890s.
      Though today much is known about the cause of the disease, a cure or effective
      treatment is not currently available. Recently the short chain fatty acid
      valproic acid, a drug used for decades in the management of epilepsy and migraine
      therapy, has been shown to elevate the levels of the essential survival motor
      neuron protein in cultured cells. In SMA mice, valproic acid diminished the
      severity of the disease phenotype. This effect was linked to the ability of the
      short chain fatty acid to suppress histone deacetylase activity and activate gene
      transcription. Since then, the study of different histone deacetylase inhibitors
      and their epigenetic modifying capabilities has been of high interest in an
      attempt to find potential candidates for effective treatment of SMA. In this
      review, we summarize the current knowledge about use of histone deacetylase
      inhibitors in SMA as well as their proposed effects on chromatin structure and
      discuss further implications for possible treatments of SMA arising from research
      examining epigenetic change.

PMID- 19383091
TI  - Different binding modes of tropeines mediating inhibition and potentiation of
      alpha1 glycine receptors.
AB  - Tropeines are bidirectional modulators of native and recombinant glycine
      receptors (GlyRs) and promising leads for the development of novel modulatory
      agents. Tropisetron potentiates and inhibits agonist-triggered GlyR currents at
      femto- to nanomolar and micromolar concentrations respectively. Here, the
      potentiating and inhibitory effects of another tropeine, 3alpha-(3'-methoxy
      benzoyloxy)nortropane (MBN) were examined by voltage-clamp electrophysiology at
      wild type and mutant alpha1 GlyRs expressed in Xenopus laevis oocytes. Several
      substitutions around the agonist-binding cavity of the alpha1 subunit interface
      (N46C, F63A, N102A, R119K, R131A, E157C, K200A, Y202L and F207A) were found to
      reduce or eliminate MBN inhibition of glycine activation. In contrast, the
      binding site mutations Q67A, R119A and S129A which did not affect MBN inhibition
      abolished the potentiation of chloride currents elicited by low concentrations of
      the partial agonist taurine following pre-incubation with MBN. Thus, potentiation
      and inhibition involve distinct binding modes of MBN in the inter-subunit agonist
      binding pocket of alpha1 GlyRs. Homology modelling and molecular dynamics
      simulations disclosed two distinct docking modes for MBN, which are consistent
      with the differential effects of individual binding site substitutions on MBN
      inhibition and potentiation respectively. Together these results suggest that
      distinct binding modes at adjacent binding sites located within the agonist
      binding pocket of the GlyR mediate the bidirectional modulatory effects of
      tropeines.

PMID- 19383089
TI  - Olfactory receptors: G protein-coupled receptors and beyond.
AB  - Sensing the chemical environment is critical for all organisms. Diverse animals
      from insects to mammals utilize highly organized olfactory system to detect,
      encode, and process chemostimuli that may carry important information critical
      for health, survival, social interactions and reproduction. Therefore, for
      animals to properly interpret and react to their environment it is imperative
      that the olfactory system recognizes chemical stimuli with appropriate
      selectivity and sensitivity. Because olfactory receptor proteins play such an
      essential role in the specific recognition of diverse stimuli, understanding how
      they interact with and transduce their cognate ligands is a high priority. In the
      nearly two decades since the discovery that the mammalian odorant receptor gene
      family constitutes the largest group of G protein-coupled receptor (GPCR) genes,
      much attention has been focused on the roles of GPCRs in vertebrate and
      invertebrate olfaction. However, is has become clear that the 'family' of
      olfactory receptors is highly diverse, with roles for enzymes and ligand-gated
      ion channels as well as GPCRs in the primary detection of olfactory stimuli.

PMID- 19383092
TI  - Specialization of the Golden2-like regulatory pathway during land plant
      evolution.
AB  - * The development of photosynthetic competence is a key requirement for all land
      plants and many aquatic algae. Previous work has demonstrated that a pair of
      Golden2-like (GLK) transcription factors regulates chloroplast development in
      diverse land plants, in that recessive glk1;glk2 mutants are pale green and fail
      to accumulate components of the light-harvesting machinery. To determine the
      extent to which the GLK pathway has diverged in land plants, we compared GLK gene
      function in the flowering plant Arabidopsis thaliana and the moss Physcomitrella
      patens. * Cross-species complementation experiments were carried out to assess
      the ability of AtGLK1 to activate downstream targets in P. patens Ppglk1;glk2
      double mutants, and the ability of upstream components in A. thaliana to activate
      PpGLK promoter::AtGLK1 coding region fusions in Atglk1;glk2 double mutants. * The
      results demonstrate that expression of the A. thaliana AtGLK1 gene cannot rescue
      the Ppglk1;glk2 mutant phenotype and that P. patens GLK promoter sequences are
      not activated in A. thaliana. * In combination with previous work which
      demonstrated partial complementation of A. thaliana double mutants by PpGlk1,
      this work provides an example of unidirectional complementation between the two
      species. This situation infers specialization of the GLK pathway during land
      plant evolution.

PMID- 19383093
TI  - Three centuries of insect outbreaks across the European Alps.
AB  - Knowledge of the persistence of regular larch budmoth outbreaks is limited in
      space and time. Although dendrochronological methods have been used to
      reconstruct insect outbreaks, their presence may be obscured by climatic
      influences. More than 5000 tree-ring series from 70 larch host and 73 spruce
      nonhost sites within the European Alps and Tatra Mountains were compiled. Site
      specific assessment of growth-climate responses and the application of six larch
      budmoth detection methods considering host, nonhost and instrumental time-series
      revealed spatiotemporal patterns of insect defoliation across the Alpine arc.
      Annual maps of reconstructed defoliation showed historical persistence of cyclic
      outbreaks at the site level, recurring c. every 8-9 yr. Larch budmoth outbreaks
      occurred independently of rising temperatures from the Little Ice Age until
      recent warmth. Although no collapse in outbreak periodicity was recorded at the
      local scale, synchronized Alpine-wide defoliation has ceased during recent
      decades. Our study demonstrates the persistence of recurring insect outbreaks
      during AD 1700-2000 and emphasizes that a widely distributed tree-ring network
      and novel analysis methods can contribute towards an understanding of the changes
      in outbreak amplitude, synchrony and climate dependence.

PMID- 19383094
TI  - Fusarium graminearum exploits ethylene signalling to colonize dicotyledonous and
      monocotyledonous plants.
AB  - Ethylene signalling affects the resistance of dicotyledonous plant species to
      diverse pathogens but almost nothing is known about the role of this pathway in
      monocotyledonous crop species. Fusarium graminearum causes Fusarium head blight
      (FHB) of cereals, contaminating grain with mycotoxins such as deoxynivalenol
      (DON). Very little is known about the mechanisms of resistance/susceptibility to
      this disease. Genetic and chemical genetic studies were used to examine the
      influence of ethylene (ET) signalling and perception on infection of
      dicotyledonous (Arabidopsis) and monocotyledonous (wheat and barley) species by
      F. graminearum. Arabidopsis mutants with reduced ET signalling or perception were
      more resistant to F. graminearum than wild-type, while mutants with enhanced ET
      production were more susceptible. These findings were confirmed by chemical
      genetic studies of Arabidopsis, wheat and barley. Attenuation of expression of
      EIN2 in wheat, a gene encoding a core component of ethylene signalling, reduced
      both disease symptoms and DON contamination of grain. Fusarium graminearum
      appears to exploit ethylene signalling in both monocotyledonous and
      dicotyledonous species. This demonstration of translation from model to crop
      species provides a foundation for improving resistance of cereal crops to FHB
      through identification of allelic variation for components of the ethylene
      signalling pathway.

PMID- 19383096
TI  - Fatty acid metabolism in the ectomycorrhizal fungus Laccaria bicolor.
AB  - Here, the genome sequence of the ectomycorrhizal basidiomycete Laccaria
      bicolorwas explored with the aim of constructing a genome-wide inventory of genes
      involved in fatty acid metabolism. Sixty-three genes of the major pathways were
      annotated and validated by the detection of the corresponding transcripts.
      Seventy-one per cent belonged to multigene families of up to five members. In the
      mycelium of L. bicolor, 19 different fatty acids were detected, including at low
      concentrations palmitvaccenic acid (16:1(11Z)), which is known to be a marker for
      arbuscular mycorrhizal fungi. The pathways of fatty acid biosynthesis and
      degradation in L. bicolor were reconstructed using lipid composition, gene
      annotation and transcriptional analysis. Annotation results indicated that
      saturated fatty acids were degraded in mitochondria, whereas degradation of
      modified fatty acids was confined to peroxisomes. Fatty acid synthase (FAS) was
      the second largest protein annotated in L. bicolor. Phylogenetic analysis
      indicated that L. bicolor, Ustilago maydis and Coprinopsis cinerea have a
      vertebrate-like type I FAS encoded as a single protein, whereas in other
      basidiomycetes, including the human pathogenic basidiomycete Cryptococcus
      neoformans, and in most ascomycetes FAS is composed of the two structurally
      distinct subunits alpha and beta.

PMID- 19383097
TI  - Radiocarbon dates reveal that Lupinus arcticus plants were grown from modern not
      Pleistocene seeds.

PMID- 19383098
TI  - Transcriptomic comparison in the leaves of two aspen genotypes having similar
      carbon assimilation rates but different partitioning patterns under elevated
      [CO2].
AB  - This study compared the leaf transcription profiles, physiological
      characteristics and primary metabolites of two Populus tremuloides genotypes
      (clones 216 and 271) known to differ in their responses to long-term elevated
      [CO2] (e[CO2]) at the Aspen free-air CO2 enrichment site near Rhinelander, WI,
      USA. The physiological responses of these clones were similar in terms of
      photosynthesis, stomatal conductance and leaf area index under e[CO2], yet very
      different in terms of growth enhancement (0-10% in clone 216; 40-50% in clone
      271). Although few genes responded to long-term exposure to e[CO2], the
      transcriptional activity of leaf e[CO2]-responsive genes was distinctly different
      between the clones, differentially impacting multiple pathways during both early
      and late growing seasons. An analysis of transcript abundance and carbon/nitrogen
      biochemistry suggested that the CO2-responsive clone (271) partitions carbon into
      pathways associated with active defense/response to stress, carbohydrate/starch
      biosynthesis and subsequent growth. The CO2-unresponsive clone (216) partitions
      carbon into pathways associated with passive defense (e.g. lignin,
      phenylpropanoid) and cell wall thickening. This study indicates that there is
      significant variation in expression patterns between different tree genotypes in
      response to long-term exposure to e[CO2]. Consequently, future efforts to improve
      productivity or other advantageous traits for carbon sequestration should include
      an examination of genetic variability in CO2 responsiveness.

PMID- 19383099
TI  - Glomus intraradices induces changes in root system architecture of rice
      independently of common symbiosis signaling.
AB  - Arbuscular mycorrhizal fungi colonize the roots of most monocotyledons and
      dicotyledons despite their different root architecture and cell patterning. Among
      the cereal hosts of arbuscular mycorrhizal fungi, Oryza sativa (rice) possesses a
      peculiar root system composed of three different types of roots: crown roots;
      large lateral roots; and fine lateral roots. Characteristic is the constitutive
      formation of aerenchyma in crown roots and large lateral roots and the absence of
      cortex from fine lateral roots. Here, we assessed the distribution of
      colonization by Glomus intraradices within this root system and determined its
      effect on root system architecture. Large lateral roots are preferentially
      colonized, and fine lateral roots are immune to arbuscular mycorrhizal
      colonization. Fungal preference for large lateral roots also occurred in sym
      mutants that block colonization of the root beyond rhizodermal penetration.
      Initiation of large lateral roots is significantly induced by G. intraradices
      colonization and does not require a functional common symbiosis signaling pathway
      from which some components are known to be needed for symbiosis-mediated lateral
      root induction in Medicago truncatula. Our results suggest variation of symbiotic
      properties among the different rice root-types and induction of the preferred
      tissue by arbuscular mycorrhizal fungi. Furthermore, signaling for arbuscular
      mycorrhizal-elicited alterations of the root system differs between rice and M.
      truncatula.

PMID- 19383100
TI  - Controls on declining carbon balance with leaf age among 10 woody species in
      Australian woodland: do leaves have zero daily net carbon balances when they die?
AB  - * Here, we evaluated how increased shading and declining net photosynthetic
      capacity regulate the decline in net carbon balance with increasing leaf age for
      10 Australian woodland species. We also asked whether leaves at the age of their
      mean life-span have carbon balances that are positive, zero or negative. * The
      net carbon balances of 2307 leaves on 53 branches of the 10 species were
      estimated. We assessed three-dimensional architecture, canopy openness,
      photosynthetic light response functions and dark respiration rate across leaf age
      sequences on all branches. We used YPLANT to estimate light interception and to
      model carbon balance along the leaf age sequences. * As leaf age increased to the
      mean life-span, increasing shading and declining photosynthetic capacity each
      separately reduced daytime carbon gain by approximately 39% on average across
      species. Together, they reduced daytime carbon gain by 64% on average across
      species. * At the age of their mean life-span, almost all leaves had positive
      daytime carbon balances. These per leaf carbon surpluses were of a similar
      magnitude to the estimated whole-plant respiratory costs per leaf. Thus, the
      results suggest that a whole-plant economic framework, including respiratory
      costs, may be useful in assessing controls on leaf longevity.

PMID- 19383101
TI  - Early gene expression programs accompanying trans-differentiation of epidermal
      cells of Vicia faba cotyledons into transfer cells.
AB  - Transfer cells (TCs) trans-differentiate from differentiated cells by developing
      extensive wall ingrowths that enhance plasma membrane transport of nutrients.
      Here, we investigated transcriptional changes accompanying induction of TC
      development in adaxial epidermal cells of cultured Vicia faba cotyledons. Global
      changes in gene expression revealed by cDNA-AFLP were compared between adaxial
      epidermal cells during induction (3 h) and subsequent building (24 h) of wall
      ingrowths, and in cells of adjoining storage parenchyma tissue, which do not form
      wall ingrowths. A total of 5795 transcript-derived fragments (TDFs) were
      detected; of these, 264 TDFs showed epidermal-specific changes in gene expression
      and a further 207 TDFs were differentially expressed in both epidermal and
      storage parenchyma cells. Genes involved in signalling (auxin/ethylene),
      metabolism (mitochondrial; storage product hydrolysis), cell division, vesicle
      trafficking and cell wall biosynthesis were specifically induced in epidermal
      TCs. Blockers of auxin action and vesicle trafficking inhibited ingrowth
      formation and marked increases in cell division accompanied TC development. Auxin
      and possibly ethylene signalling cascades induce epidermal cells of V. faba
      cotyledons to trans-differentiate into TCs. Trans-differentiation is initiated by
      rapid de-differentiation to a mitotic state accompanied by mitochondrial
      biogenesis driving storage product hydrolysis to fuel wall ingrowth formation
      orchestrated by a modified vesicle trafficking mechanism.

PMID- 19383102
TI  - Possible role of early flowering 3 (ELF3) in clock-dependent floral regulation by
      short vegetative phase (SVP) in Arabidopsis thaliana.
AB  - Circadian clock proteins play key roles in adaptations of plants to diurnal
      environmental conditions. The photoperiodic flowering response is one of the
      mechanisms of adaptation to seasonal changes in the lengths of day and night.
      Double mutations in two clock genes, late elongated hypocotyl (LHY) and circadian
      clock associated 1 (CCA1), accelerated flowering under short days (SDs) but
      delayed flowering under continuous light (LL) in Arabidopsis thaliana. The
      mechanism underlying the late flowering of lhy;cca1 mutants under LL was
      investigated here. Late flowering of plants with overexpression of short
      vegetative phase (SVP) was much more pronounced under SDs and enhanced by
      constans 2 (co-2) under long days (LDs), suggesting that SVP and CO act
      independently in the photoperiodic flowering pathway. However, how SVP and
      flowering locus C (FLC) mediated the effects of LHY/CCA1 and thus influenced
      flowering time was not completely clear. A mutant line lhy;cca1 in the Landsberg
      erecta (Ler) background was established, ethyl methanesulfonate (EMS)-mutagenized
      and used to screen suppressors of late flowering of lhy;cca1 under LL. Mutations
      in the clock gene early flowering 3 (ELF3) were identified as suppressors.
      Overexpression and loss-of-function of ELF3 influenced SVP protein accumulation.
      Therefore, we propose that, as well as the classical GIGANTEA (GI)-CO pathway,
      LHY/CCA1 regulates a pathway negatively controlling flowering locus T (FT),
      possibly via ELF3-SVP/FLC.

PMID- 19383103
TI  - The Populus Genome Integrative Explorer (PopGenIE): a new resource for exploring
      the Populus genome.
AB  - Populus has become an important model plant system. However, utilization of the
      increasingly extensive collection of genetics and genomics data created by the
      community is currently hindered by the lack of a central resource, such as a
      model organism database (MOD). Such MODs offer a single entry point to the
      collection of resources available within a model system, typically including
      tools for exploring and querying those resources. As a starting point to
      overcoming the lack of such an MOD for Populus, we present the Populus Genome
      Integrative Explorer (PopGenIE), an integrated set of tools for exploring the
      Populus genome and transcriptome. The resource includes genome, synteny and
      quantitative trait locus (QTL) browsers for exploring genetic data. Expression
      tools include an electronic fluorescent pictograph (eFP) browser, expression
      profile plots, co-regulation within collated transcriptomics data sets, and
      identification of over-represented functional categories and genomic hotspot
      locations. A number of collated transcriptomics data sets are made available in
      the eFP browser to facilitate functional exploration of gene function. Additional
      homology and data extraction tools are provided. PopGenIE significantly increases
      accessibility to Populus genomics resources and allows exploration of
      transcriptomics data without the need to learn or understand complex statistical
      analysis methods. PopGenIE is available at www.popgenie.org or via
      www.populusgenome.info.

PMID- 19383104
TI  - Cyanogenic myrmecophytes, redundant defence mechanisms and complementary defence
      syndromes: revisiting the neotropical ant-acacias.

PMID- 19383105
TI  - Patterns in root trait variation among 25 co-existing North American forest
      species.
AB  - Ephemeral roots have essential roles in plant and ecosystem functioning. In
      forests, roots account for a major component of carbon cycling, yet few studies
      have examined ranges of root trait variation and how different species vary in
      root form and function in these communities. Root branching intensity, specific
      root length (SRL; root length per unit dry mass), root diameter, tissue density,
      phenolic concentration and nitrogen concentration were determined for the finest
      two root orders of 25 co-existing North American woody species sampled from
      mature plants in a single forest community. Trait correlations and multivariate
      patterns were examined to evaluate the most important trait differences among
      species. Branching intensity, SRL, and phenolic concentration varied most widely
      among species (coefficient of variation (CV) = 0.42, 0.57 and 0.58,
      respectively). Species predominately forming ectomycorrhiza (EM) had a higher
      branching intensity than those forming arbuscular mycorrhiza (AM) with
      mycorrhizal types correctly predicted in c. 70% of individual observations by
      branching intensity alone. There was notably no correlation between SRL and
      nitrogen. Variation in SRL among species mapped partially along phylogenetic
      lines (consistency index (CI) = 0.44), with remaining variation attributable to
      differences in species' ecological specialization. Variation found in root traits
      suggests different nutrient acquisition strategies within this community, which
      could have potential species-level effects on carbon and mineral nutrient
      cycling.

PMID- 19383106
TI  - RPW8 and resistance to powdery mildew pathogens in natural populations of
      Arabidopsis lyrata.
AB  - It is not clear to what extent the orthologues of genes that are adaptively
      important in one species also contribute to adaptive variation in others. Here,
      we examine Arabidopsis lyrata to assess the functional and evolutionary
      significance of natural variation in an orthologue of the gene RPW8 known to be a
      major determinant of powdery mildew resistance in Arabidopsis thaliana. We
      assessed the sequence variation at RPW8 and the associated resistance reaction in
      populations of A. lyrata ssp. petraea. Neutrality tests were performed to
      understand the importance of local adaptation in maintaining variation at the
      locus. Highly truncated RPW8 proteins were frequent in all populations and were
      associated with an increased risk of susceptibility. Haplotypes encoding full
      length proteins were highly significantly associated with resistance. There were
      no signatures of selection at the species-wide level, but some evidence for
      positive selection in two populations. RPW8 in A. lyrata appears to have a role
      in powdery mildew resistance, similar to its orthologue in A. thaliana. Unlike A.
      thaliana, A. lyrata contains a genetic component that can act independently of
      RPW8 to confer resistance to powdery mildew pathogens. Infrequent local selective
      sweeps may favour different alleles in different populations, and thereby
      contribute to the maintenance of species-wide variation at the locus.

PMID- 19383107
TI  - Pollen donor composition during the early phases of reproduction  revealed by DNA
      genotyping of pollen grains and seeds of Castanea  crenata.
AB  - In plants, pollen donor composition can differ during the early phases of
      reproduction through various selection mechanisms favouring self, related or
      nonrelated pollen donors, but such differences have not been examined under
      natural conditions because paternity is difficult to analyse in a natural
      setting. Here, we performed paternity analyses based on microsatellite genotyping
      of individual pollen grains deposited on female flowers (n = 773) and seeds (n =
      304) to evaluate pollen donor composition from three individuals of the insect
      pollinated monoecious tree Castanea crenata in a natural forest. Spatial genetic
      structure was also investigated. A mean self-pollen rate of 90.2% was observed at
      the pollination stage, but a low selfing rate of 0.3% was observed at the seed
      stage. In outcross events, however, pairwise distance and relatedness between
      maternal and paternal parents were not different between pollination and seed
      stages. We also observed significant positive relatedness, based on clear fine
      scale genetic structure of individual trees within 80 m of one another, and 71%
      of seeds were derived using pollen grains of related trees within 80 m. The
      results suggest that the mechanism of self-incompatibility strongly avoids self
      pollen before seed production. However, the avoidance of biparental inbreeding
      was not obvious between pollination and seed stages.

PMID- 19383108
TI  - Using heterozygosity to estimate a percentage DNA sequence similarity for
      environmental species' delimitation across basidiomycete fungi.

PMID- 19383109
TI  - Ant-plants and fungi: a new threeway symbiosis.
AB  - Symbioses between plants and fungi, fungi and ants, and ants and plants all play
      important roles in ecosystems. Symbioses involving all three partners appear to
      be rare. Here, we describe a novel tripartite symbiosis in which ants and a
      fungus inhabit domatia of an ant-plant, and present evidence that such
      interactions are widespread. We investigated 139 individuals of the African ant
      plant Leonardoxa africana for occurrence of fungus. Behaviour of mutualist ants
      toward the fungus within domatia was observed using a video camera fitted with an
      endoscope. Fungi were identified by sequencing a fragment of their ribosomal DNA.
      Fungi were always present in domatia occupied by mutualist ants but never in
      domatia occupied by opportunistic or parasitic ants. Ants appear to favour the
      propagation, removal and maintenance of the fungus. Similar fungi were associated
      with other ant-plants in Cameroon. All belong to the ascomycete order
      Chaetothyriales; those from L. africana formed a monophyletic clade. These new
      plant-ant-fungus associations seem to be specific, as demonstrated within
      Leonardoxa and as suggested by fungal phyletic identities. Such tripartite
      associations are widespread in African ant-plants but have long been overlooked.
      Taking fungal partners into account will greatly enhance our understanding of
      symbiotic ant-plant mutualisms.

PMID- 19383111
TI  - Obliterative bronchiolitis in lung allografts removed at retransplant for
      intractable airway problems.
AB  - BACKGROUND AND OBJECTIVE: The role of large airway ischaemia, with resultant
      airway narrowing, in the development of post-lung transplant bronchiolitis
      obliterans has not been defined. A determination of clinical bronchiolitis
      obliterans syndrome (BOS), which is defined as a decline in FEV(1) from a stable
      post-transplant baseline, is difficult in the setting of airway complications.
      The aim of this study was to assess the evidence for histological bronchiolitis
      obliterans in lung allografts removed during retransplantation for severe
      recurrent airway narrowing. METHODS: Case records and histological findings in
      allograft lungs removed at retransplantation were retrospectively reviewed.
      RESULTS: Five lung transplant recipients, who had undergone retransplantation
      because of severe recalcitrant airway stenosis, were identified. In each case,
      explant allograft lung pathology revealed evidence of bronchiolitis obliterans.
      CONCLUSIONS: There is a possible link between airway ischaemia, large airway
      stenosis and the development of bronchiolitis obliterans, which is the most
      common cause of death in lung transplant recipients after the first year. These
      findings may provide an impetus for evaluation of the role of bronchial artery
      revascularization techniques in the prevention of bronchiolitis obliterans.

PMID- 19383110
TI  - Asthma Control Test correlates well with the treatment decisions made by asthma
      specialists.
AB  - BACKGROUND AND OBJECTIVE: Poor assessment of asthma control results in suboptimal
      treatment. Identifying parameters that accurately assess control will benefit
      treatment decisions. The Asthma Control Test (ACT) is a five-item questionnaire
      for the assessment of asthma control. This study evaluated its correlation with
      the treatment decisions made by asthma specialists in an outpatient clinic
      setting, and compared its performance with other conventional parameters
      including spirometry, PEF rate (PEFR), fractional exhaled nitric oxide (FeNO) and
      BHR. METHODS: The 383 (122 men) study subjects completed a 1-month diary on
      symptoms and PEFR before the assessment. All subjects then completed the ACT
      together with same-day spirometry and FeNO measurement. BHR to methacholine was
      performed in 73 subjects in the week before assessment. Asthma specialists,
      blinded to the results of the ACT, FeNO and BHR (but not spirometry and PEFR),
      assessed the patients' level of control according to the 2006 version of the
      Global Initiative for Asthma guidelines and made appropriate treatment decision.
      RESULTS: The group mean (SD) age was 46.1 (13.4) years with pre-bronchodilator
      FEV(1) 84.72 (20.81) % predicted. Receiver operating characteristic (ROC) curve
      analysis found that an ACT score of < or = 20 best correlated with uncontrolled
      asthma (area under curve (AUC) = 0.76) with a sensitivity of 70.5%, specificity
      76.0%, positive predictive value 76.2% and negative predictive value 70.2% for
      predicting step-up of asthma therapy. On ROC analysis, the ACT score had the
      highest AUC (0.81 (P < 0.001)) for changing asthma therapy when compared with
      FeNO, spirometry, PEFR and BHR parameters CONCLUSIONS: The ACT correlated better
      with treatment decisions made by asthma specialists than spirometry, PEFR and
      FeNO.

PMID- 19383112
TI  - Acute effects of hyperoxia on resting pattern of ventilation and dyspnoea in
      COPD.
AB  - BACKGROUND AND OBJECTIVE: Hyperoxia has been shown to reduce resting ventilation,
      hyperinflation and dyspnoea in patients with severely hypoxaemic COPD. This study
      assessed the effects of hyperoxia on these resting measures in patients with COPD
      of varying disease severity and characterized those patients who responded.
      METHODS: Measurements of dyspnoea (Borg score), oxyhaemoglobin saturation
      (SpO(2)), inspiratory capacity (IC), minute ventilation, tidal volume, breathing
      and cardiac frequency were performed at rest in 51 patients with COPD while they
      breathed air and 44% oxygen, in a randomized double-blinded fashion. RESULTS:
      Hyperoxia induced significant reductions in cardiac frequency and dyspnoea and a
      significant increase in SpO(2). No significant change was noted in IC for the
      group overall, and there was substantial inter-subject variation in this
      measurement. No significant changes were found in ventilation, and there was no
      correlation between change in dyspnoea and change in IC. In patients with
      moderate to severe airflow obstruction (FEV(1) < 70% predicted), a significant
      association was found between the degree of airflow obstruction and change in IC
      induced by hyperoxia. CONCLUSIONS: Hyperoxia improved dyspnoea but did not
      significantly alter resting pulmonary hyperinflation in a group of patients with
      COPD of varying severity. However, in a subset patients with moderate to severe
      airflow obstruction a relationship existed between the severity of airflow
      obstruction and volume response to hyperoxia.

PMID- 19383113
TI  - Natural stent in the management of post-intubation tracheal stenosis.
AB  - BACKGROUND AND OBJECTIVE: The treatment choice for post-intubation tracheal
      stenosis (PITS) in patients for whom surgery is not initially feasible is
      bronchoscopic silicone stenting. A new silicone stent, called the Natural stent
      (N stent), was investigated for its clinical efficacy and safety in patients with
      PITS. METHODS: A retrospective review was conducted of 32 patients with PITS who
      underwent N stenting between November 2001 and December 2006 and were followed
      for at least 12 months. RESULTS: Airway dilatation with combined modalities such
      as Nd:YAG laser, ballooning or bougienage was followed by N stent insertion.
      After intervention, all patients had symptomatic and spirometric improvement
      without immediate complications. Removal of the stent without re-stenosis was
      successful in 38% of the patients at a median time of 7 months after insertion.
      The stent could not be removed or needed reinsertion in 31% of patients, and 16%
      of patients underwent surgery after initial stabilization by stenting. Late
      complications were stent migration (34%), mucostasis (31%), granulation tissue
      formation (38%) and re-stenosis (40%). All patients tolerated the management of
      complications during a median follow up of 22 months. CONCLUSIONS: Bronchoscopic
      N stenting is an effective treatment for patients with PITS in whom surgery is
      not feasible on initial presentation. Further stent development is necessary to
      reduce the late complication rate.

PMID- 19383114
TI  - Observations on environmental asbestos exposure in a high risk area.
AB  - BACKGROUND AND OBJECTIVE: Environmental asbestos exposure is causally associated
      with various pulmonary pathologies. In Turkey, one of the most important sources
      of asbestos exposure is dust originating from the walls of homes whitewashed with
      white stucco. The main asbestos types implicated are tremolite and, to a lesser
      extent, chrysotile. This study investigated the presence and effect of
      environmental asbestos exposure in a small village in Isparta, Turkey. METHODS:
      Samples of asbestos mine ore, whitewashed plaster from the interior walls of the
      houses and whitesoil from the outside walls of the houses were analysed. Chest
      radiographs of 132 villagers aged 30 years and over and living in the village
      during the study were obtained. Verbal histories from the relatives of people who
      had died from lung cancer or mesothelioma and hospital records contributed 13
      cases to the study population, giving a total of 145 cases under study. RESULTS:
      Chrysotile fibres were found in the old asbestos mine sample, and zeolite in the
      whitesoil sample from the outside walls. Abnormal CXR were found in 19 subjects
      (14. 4%), the most common being pleural calcifications and/or pleural plaques (n
      = 14, 10.6%). A further five subjects with pleural calcifications and/or pleural
      plaques were identified from verbal autopsy and hospital records. Malignant
      pleural mesothelioma was present in one living subject and four of the deaths. A
      possible familial clustering of lung cancer and malignant mesothelioma was noted.
      CONCLUSION: While tremolite asbestos is the asbestos found in most white soil in
      Turkey, in this village chrysotile asbestos was found in the white soil. Familial
      clustering may indicate genetic susceptibility or increased environmental
      exposure in some families.

PMID- 19383115
TI  - Changing patterns in interventional bronchoscopy.
AB  - BACKGROUND AND OBJECTIVE: Many interventional tools for airway disorders can now
      be delivered via flexible bronchoscopy (FB), including neodymium-yttrium
      aluminium garnet laser, electrocautery, argon plasma coagulation, cryotherapy,
      balloon dilatation and metal or hybrid stents. Comparison of outcomes for
      patients undergoing rigid bronchoscopy (RB) with those treated using FB
      highlights the usefulness of the FB approach. METHODS: A retrospective medical
      record review of all interventional bronchoscopy procedures performed at Lahey
      Clinic over the past 8 years was conducted. Patients were categorized into two
      groups according to the procedure used, that is, RB (251 patients), and FB (161
      patients) groups. Patients with malignancies were included as a separate
      subgroup, comprising 178 RB and 117 FB patients. For every procedure, the
      location of the lesion, patient survival from the first interventional procedure
      performed, and in patients with malignancy, additional treatments received such
      as chemotherapy and radiation were recorded. RESULTS: Ninety per cent of RB
      procedures were performed in patients with tracheal or main stem lesions, while
      over half the patients undergoing FB had more distal lesions. A trend towards
      increasing use of FB for interventional procedures in recent years was noted.
      CONCLUSIONS: FB is a valuable alternative to RB for treating less advanced
      malignant disease or distal airway lesions.

PMID- 19383116
TI  - Reasons of general practitioners for not prescribing lipid-lowering medication to
      patients with diabetes: a qualitative study.
AB  - BACKGROUND: Lipid-lowering medication remains underused, even in high-risk
      populations. The objective of this study was to determine factors underlying
      general practitioners' decisions not to prescribe such drugs to patients with
      type 2 diabetes. METHODS: A qualitative study with semi-structured interviews
      using real cases was conducted to explore reasons for not prescribing lipid
      lowering medication after a guideline was distributed that recommended the use of
      statins in most patients with type 2 diabetes. Seven interviews were conducted
      with general practitioners (GPs) in The Netherlands, and analysed using an
      analytic inductive approach. RESULTS: Reasons for not-prescribing could be
      divided into patient and physician-attributed factors. According to the GPs, some
      patients do not follow-up on agreed medication and others object to taking lipid
      lowering medication, partly for legitimate reasons such as expected or perceived
      side effects. Furthermore, the GPs themselves perceived reservations for
      prescribing lipid-lowering medication in patients with short life expectancy,
      expected compliance problems or near goal lipid levels. GPs sometimes postponed
      the start of treatment because of other priorities. Finally, barriers were seen
      in the GPs' practice organisation, and at the primary-secondary care interface.
      CONCLUSION: Some of the barriers mentioned by GPs seem to be valid reasons,
      showing that guideline non-adherence can be quite rational. On the other hand,
      treatment quality could improve by addressing issues, such as lack of knowledge
      or motivation of both the patient and the GP. More structured management in
      general practice may also lead to better treatment.

PMID- 19383117
TI  - Is vitamin D deficiency involved in the immune reconstitution inflammatory
      syndrome?
AB  - BACKGROUND: About 20-30% of persons with HIV infection, especially those living
      in countries with limited resources, experience an immune reconstitution
      inflammatory syndrome (IRIS) after starting antiretroviral treatment. The active
      form of vitamin D, 1,25-dihydroxyvitamin D, is a key player in the clearance of
      pathogens and influences the level of inflammation and macrophage activation.
      PRESENTATION OF THE HYPOTHESIS: We hypothesize that low availability of 1,25
      dihydroxyvitamin D, either due to vitamin D deficiency or due to polymorphisms in
      the vitamin D receptor or in its activating/inactivating enzymes, contributes to
      the appearance of IRIS. Furthermore, drug interactions with the enzymatic
      pathways of vitamin D could favour the development of IRIS. TESTING THE
      HYPOTHESIS: Our hypothesis could be explored by a case-control study to assess
      the prevalence of vitamin D deficiency in HIV-infected patients on antiretroviral
      treatment who develop and do not develop IRIS. IMPLICATIONS OF THE HYPOTHESIS: If
      the role of vitamin D in IRIS is confirmed, we would be able to screen patients
      at risk for IRIS by screening for vitamin D deficiency. After confirmation by
      means of a clinical trial, vitamin D supplementation could be a cheap and safe
      way to reduce the incidence of IRIS.

PMID- 19383118
TI  - Morphological features and differential counts of Plasmodium knowlesi parasites
      in naturally acquired human infections.
AB  - BACKGROUND: Human infections with Plasmodium knowlesi, a simian malaria parasite,
      are more common than previously thought. They have been detected by molecular
      detection methods in various countries in Southeast Asia, where they were
      initially diagnosed by microscopy mainly as Plasmodium malariae and at times, as
      Plasmodium falciparum. There is a paucity of information on the morphology of P.
      knowlesi parasites and proportion of each erythrocytic stage in naturally
      acquired human infections. Therefore, detailed descriptions of the morphological
      characteristics and differential counts of the erythrocytic stages of P. knowlesi
      parasites in human infections were made, photographs were taken, and
      morphological features were compared with those of P. malariae and P. falciparum.
      METHODS: Thick and thin blood films were made prior to administration of anti
      malarial treatment in patients who were subsequently confirmed as having single
      species knowlesi infections by PCR assays. Giemsa-stained blood films, prepared
      from 10 randomly selected patients with a parasitaemia ranging from 610 to
      236,000 parasites per microl blood, were examined. RESULTS: The P. knowlesi
      infection was highly synchronous in only one patient, where 97% of the parasites
      were at the late trophozoite stage. Early, late and mature trophozoites and
      schizonts were observed in films from all patients except three; where schizonts
      and early trophozoites were absent in two and one patient, respectively.
      Gametocytes were observed in four patients, comprising only between 1.2 to 2.8%
      of infected erythrocytes. The early trophozoites of P. knowlesi morphologically
      resemble those of P. falciparum. The late and mature trophozoites, schizonts and
      gametocytes appear very similar to those of P. malariae. Careful examinations
      revealed that some minor morphological differences existed between P. knowlesi
      and P. malariae. These include trophozoites of knowlesi with double chromatin
      dots and at times with two or three parasites per erythrocyte and mature
      schizonts of P. knowlesi having 16 merozoites, compared with 12 for P. malariae.
      CONCLUSION: Plasmodium knowlesi infections in humans are not highly synchronous.
      The morphological resemblance of early trophozoites of P. knowlesi to P.
      falciparum and later erythrocytic stages to P. malariae makes it extremely
      difficult to identify P. knowlesi infections by microscopy alone.

PMID- 19383119
TI  - Expression levels of immune markers in Actinobacillus pleuropneumoniae infected
      pigs and their relation to breed and clinical symptoms.
AB  - BACKGROUND: In pigs little is known about the role of innate immune defence in
      bacterial infections of the respiratory tract, despite their major role in pig
      production. In the present study we characterized and compared in vitro and in
      vivo activation of immune markers of different pig breeds 7 days before, and 4
      and 21 days after an experimental aerosol infection with Actinobacillus (A.)
      pleuropneumoniae. RESULTS: In vitro stimulation of bronchoalveolar lavage fluid
      (BALF) and blood leukocytes with A. pleuropneumoniae, Streptococcus suis, PMA and
      LPS led to production of different amounts of H2O2, NO and TNF-alpha, depending
      on the stimulus, individual, breed and time of infection. Generally, significant
      responses to in vitro stimulation were observed only in blood leukocytes, whereas
      the alveolar macrophages showed a high basal activation. In addition, the
      production of haptoglobin and cytokines (TNF-alpha, IFN-gamma and IL-10) in vivo
      was measured in plasma and BALF. Plasma haptoglobin levels mirrored the clinical
      manifestations at 4 days post-infection. In plasma and BALF TNF-alpha could not
      be detected, whereas variable levels of IFN-gamma were found at pre- and post
      infection times. IL-10 was found in some plasma but in none of the BALF samples.
      The different expression levels in individuals within the breeds correlated for
      some markers with the severity of clinical manifestations, e.g. H2O2, plasma
      haptoglobin and BALF IFN-gamma for German Landrace pigs. CONCLUSION: Our findings
      revealed differences in the activation of the immune markers with respect to
      infection time, individuals and breeds. Moreover, results showed different
      correlation grades between the immune markers produced in vitro or in vivo and
      the clinical manifestations. Further analyses will have to show whether these
      markers may serve as correlates of protection against porcine respiratory
      infections.

PMID- 19383121
TI  - Centrosome proteins form an insoluble perinuclear matrix during muscle cell
      differentiation.
AB  - BACKGROUND: Muscle fibres are formed by elongation and fusion of myoblasts into
      myotubes. During this differentiation process, the cytoskeleton is reorganized,
      and proteins of the centrosome re-localize to the surface of the nucleus. The
      exact timing of this event, and the underlying molecular mechanisms are still
      poorly understood. RESULTS: We performed studies on mouse myoblast cell lines
      that were induced to differentiate in culture, to characterize the early events
      of centrosome protein re-localization. We demonstrate that this re-localization
      occurs already at the single cell stage, prior to fusion into myotubes.
      Centrosome proteins that accumulate at the nuclear surface form an insoluble
      matrix that can be reversibly disassembled if isolated nuclei are exposed to
      mitotic cytoplasm from Xenopus egg extract. Our microscopy data suggest that this
      perinuclear matrix of centrosome proteins consists of a system of interconnected
      fibrils. CONCLUSION: Our data provide new insights into the reorganization of
      centrosome proteins during muscular differentiation, at the structural and
      biochemical level. Because we observe that centrosome protein re-localization
      occurs early during differentiation, we believe that it is of functional
      importance for the reorganization of the cytoskeleton in the differentiation
      process.

PMID- 19383120
TI  - A novel Respiratory Health Score (RHS) supports a role of acute lung damage and
      pig breed in the course of an Actinobacillus pleuropneumoniae infection.
AB  - BACKGROUND: Bacterial lung infections are a major cause of economic losses in the
      pig industry; they are responsible for approximately 50% of the antibiotics used
      in pigs and, therefore, also present an increasing concern to consumer protection
      agencies. In response to this changing market we investigated the feasibility of
      an old approach aimed at the breeding selection of more resistant pigs. As a
      first step in this direction we applied a new respiratory health score system to
      study the susceptibility of four different pig breeding lines (German Landrace,
      Pietrain, Hampshire, Large White) towards the respiratory tract pathogen
      Actinobacillus (A.) pleuropneumoniae. RESULTS: A controlled experimental aerosol
      infection with an A. pleuropneumoniae serotype 7 isolate was performed using 106
      weaning pigs of defined breeding lines from the breeds German Landrace, Pietrain,
      Hamphire, and Large White. Pigs were clinically assessed on days 4 and 20 post
      infection following a novel scoring system, the Respiratory Health Score (RHS),
      which combines clinical, sonographic and radiographic examination results. The
      ranking on day 4 was significantly correlated with the ranking based on the
      pathomorphological Lung Lesion Score (LLS; Spearman Rank Correlation Coefficient
      of 0.86 [p < 0.0001]). Based on their RHS pigs were assigned to the different
      quartiles independent of the breeding line. The RHS-based rankings of pigs on day
      4 and on day 20 were highly correlated (Spearman Rank Correlation Coefficient of
      0.82 [p < 0.0001]) independent of the breeding line. Pigs of the Hampshire line
      were predominantly found in the lowest scoring quartile (47.6%) and absent in the
      highest scoring quartile. In contrast, pigs of the German Landrace and Pietrain
      breeding lines were predominantly found in the highest scoring quartile (32.3%
      and 35.7%, respectively). CONCLUSION: These results demonstrate that the RHS
      obtained from live pigs shows a highly significant correlation to the lung lesion
      score considered as a "gold standard". The correlation of the ranking at days 4
      and 20 post infection implies that the course of disease is highly dependent on
      the acute lung damage. The different severity of signs among the tested pig
      breeding lines clearly suggests a genetic difference in the susceptibility of
      pigs to A. pleuropneumoniae infection.

PMID- 19383122
TI  - Risk and prognostic significance of tuberculosis in patients from The TREAT Asia
      HIV Observational Database.
AB  - BACKGROUND: To assess the risk and the prognostic significance of tuberculosis
      (TB) diagnosis in patients from The TREAT Asia HIV Observational Database, a
      multi-centre prospective cohort of HIV-infected patients receiving HIV care in
      the Asia-Pacific region. METHODS: The risk of TB diagnosis after recruitment was
      assessed in patients with prospective follow-up. TB diagnosis was fitted as a
      time-dependent variable in assessing overall survival. RESULTS: At baseline, 22%
      of patients were diagnosed with TB. TB incidence was 1.98 per 100 person-years
      during follow up, with predictors including younger age, lower recent CD4 count,
      duration of antiretroviral treatment, and living in high TB burden countries.
      Among 3279 patients during 6968 person-years, 142 died (2.04 per 100 person
      years). Compared to patients with CDC category A or B illness only, mortality was
      marginally higher in patients with single Non-TB AIDS defining illness (ADI), or
      TB only (adjusted HR 1.35, p = 0.173) and highest in patients with multiple non
      TB AIDS or both TB and other ADI (adjusted HR 2.21, p < 0.001). CONCLUSION: The
      risk of TB diagnosis was associated with increasing immunodeficiency and partly
      reduced by antiretroviral treatment. The prognosis of developing TB appeared to
      be similar to that following a diagnosis of other non-TB ADI.

PMID- 19383123
TI  - Return to work of breast cancer survivors: a systematic review of intervention
      studies.
AB  - BACKGROUND: Breast cancer management has improved dramatically in the past three
      decades and as a result, a population of working age women is breast cancer
      survivor. Interventions for breast cancer survivors have shown improvements in
      quality of life and in physical and psychological states. In contrast, efforts
      aimed at stimulating re-employment and return-to-work interventions for breast
      cancer survivors have not kept pace. The objective of this review was to study
      the effects and characteristics of intervention studies on breast cancer
      survivors in which the outcome was return to work. METHODS: The Cochrane
      Controlled Trials Register (The Cochrane Library, Issue 4, 2006), Medline, Ovid,
      EMBASE and PsychInfo were systematically searched for studies conducted between
      1970 to February 2007. Intervention studies for female breast cancer survivors
      that were focused on return to work were included. RESULTS: Our search strategy
      identified 5219 studies. Four studies out of 100 potentially relevant abstracts
      were selected and included 46-317 employed women who had had mastectomy, adjuvant
      therapy and rehabilitation, with the outcome return to work. The intervention
      programs focused on improvement of physical, psychological and social recovery.
      Although a substantial percentage (between 75% to 85%) of patients included in
      these studies returned to work after rehabilitation, it is not clear whether this
      proportion would have been lower for patients without counseling or exercise, or
      any other interventions, as three out of four studies did not include a
      comparison group. CONCLUSION: The most important finding of this review is the
      lack of methodologically sound intervention studies on breast cancer survivors
      with the outcome return to work. Using evidence from qualitative and
      observational studies on cancer and the good results of intervention studies on
      return to work programs and vocational rehabilitation, return to work
      interventions for breast cancer survivors should be further developed and
      evaluated.

PMID- 19383124
TI  - Mitochondrial DNA haplogroup T is associated with coronary artery disease and
      diabetic retinopathy: a case control study.
AB  - BACKGROUND: There is strong and consistent evidence that oxidative stress is
      crucially involved in the development of atherosclerotic vascular disease.
      Overproduction of reactive oxygen species (ROS) in mitochondria is an unifying
      mechanism that underlies micro- and macrovascular atherosclerotic disease. Given
      the central role of mitochondria in energy and ROS production, mitochondrial DNA
      (mtDNA) is an obvious candidate for genetic susceptibility studies on
      atherosclerotic processes. We therefore examined the association between mtDNA
      haplogroups and coronary artery disease (CAD) as well as diabetic retinopathy.
      METHODS: This study of Middle European Caucasians included patients with
      angiographically documented CAD (n = 487), subjects with type 2 diabetes mellitus
      with (n = 149) or without (n = 78) diabetic retinopathy and control subjects
      without clinical manifestations of atherosclerotic disease (n = 1527). MtDNA
      haplotyping was performed using multiplex PCR and subsequent multiplex primer
      extension analysis for determination of the major European haplogroups.
      Haplogroup frequencies of patients were compared to those of control subjects
      without clinical manifestations of atherosclerotic disease. RESULTS: Haplogroup T
      was significantly more prevalent among patients with CAD than among control
      subjects (14.8% vs 8.3%; p = 0.002). In patients with type 2 diabetes, the
      presence of diabetic retinopathy was also significantly associated with a higher
      prevalence of haplogroup T (12.1% vs 5.1%; p = 0.046). CONCLUSION: Our data
      indicate that the mtDNA haplogroup T is associated with CAD and diabetic
      retinopathy in Middle European Caucasian populations.

PMID- 19383125
TI  - Mobile and cordless telephones, serum transthyretin and the blood-cerebrospinal
      fluid barrier: a cross-sectional study.
AB  - BACKGROUND: Whether low-intensity radiofrequency radiation damages the blood
      brain barrier has long been debated, but little or no consideration has been
      given to the blood-cerebrospinal fluid barrier. In this cross-sectional study we
      tested whether long-term and/or short-term use of wireless telephones was
      associated with changes in the serum transthyretin level, indicating altered
      transthyretin concentration in the cerebrospinal fluid, possibly reflecting an
      effect of radiation. METHODS: One thousand subjects, 500 of each sex aged 18-65
      years, were randomly recruited using the population registry. Data on wireless
      telephone use were assessed by a postal questionnaire and blood samples were
      analyzed for serum transthyretin concentrations determined by standard
      immunonephelometric techniques on a BN Prospec instrument. RESULTS: The response
      rate was 31.4%. Logistic regression of dichotomized TTR serum levels with a cut
      point of 0.31 g/l on wireless telephone use yielded increased odds ratios that
      were statistically not significant. Linear regression of time since first use
      overall and on the day that blood was withdrawn gave different results for males
      and females: for men significantly higher serum concentrations of TTR were seen
      the longer an analogue telephone or a mobile and cordless desktop telephone
      combined had been used, and in contrast, significantly lower serum levels were
      seen the longer an UMTS telephone had been used. Adjustment for fractions of use
      of the different telephone types did not modify the effect for cumulative use or
      years since first use for mobile telephone and DECT, combined. For women, linear
      regression gave a significant association for short-term use of mobile and
      cordless telephones combined, indicating that the sooner blood was withdrawn
      after the most recent telephone call, the higher the expected transthyretin
      concentration. CONCLUSION: In this hypothesis-generating descriptive study time
      since first use of mobile telephones and DECT combined was significantly
      associated with higher TTR levels regardless of how much each telephone type had
      been used. Regarding short-term use, significantly higher TTR concentrations were
      seen in women the sooner blood was withdrawn after the most recent telephone call
      on that day.

PMID- 19383126
TI  - A country-wide malaria survey in Mozambique. II. Malaria attributable proportion
      of fever and establishment of malaria case definition in children across
      different epidemiological settings.
AB  - BACKGROUND: Protection against clinical malaria episodes is acquired slowly after
      frequent exposure to malaria parasites. This is reflected by a decrease with
      increasing age in both parasite density and incidence of clinical episodes. In
      many settings of stable malaria transmission, the presence of asymptomatic
      malaria parasite carriers is common and the definition of clinical malaria
      remains uncertain. METHODS: Between February 2002 and April 2003, a country-wide
      malaria survey was conducted in 24 districts of Mozambique, aiming to
      characterize the malaria transmission intensities and to estimate the proportion
      of fever cases attributable to malaria infections in order to establish the
      malaria case definition. A total of 8,816 children less than ten years of age
      were selected for the study. Axillary temperature was measured in all
      participating subjects and finger prick blood collections were taken to prepare
      thick and thin films for identification of parasite species and determination of
      parasite density. The proportion of fever cases attributable to malaria infection
      was estimated using a logistic regression of the fever on a monotonic function of
      the parasite density and, using bootstrap facilities, bootstrapped estimated
      confidence intervals, as well as the sensitivity and specificity for different
      parasite density cut-offs were produced. RESULTS: Overall, the prevalence of
      Plasmodium falciparum was 52.4% (4,616/8,816). The prevalence of fever (axillary
      temperature >or= 37.5 degrees C) was 9.4% (766/8,816). Fever episodes peaked
      among children below 12 months of life [15.1% (206/1,517)]. The lowest fever
      prevalence of 5.9% (67/1,224) was recorded amongst children between five and
      seven years of age. Among 4,098 parasitized children, 498/4,098 (13.02%) had
      fever. The prevalence of malaria infections associated with fever peaked among
      children in the less than twelve months age group and thereafter decreased
      rapidly with increasing age (p < 0.001). High parasite densities were
      significantly associated with fever (p < 0.04). The proportion of fever
      attributed to malaria was 37.8% (95% CI 32.9% - 42.7%). An age-specific pattern
      was observed with significant variations across different regions in the country.
      In general, among children less than 12 months of life, the proportion of fever
      attributed to malaria infection was 43.5% (95% CI 25.8% - 61.2%), in children
      aged between 12 and 59 months of age was 39.6% (95% CI 30.3% - 48.9%), and among
      children aged between 5 and 10 years old was 21.5% (95% CI 11.6% - 31.4%).
      CONCLUSION: This study confirms that malaria remains a major cause of febrile
      illness during childhood. It also defines the relation between parasite density
      and fever and how this varies with age and region. This may help guide case
      definition for clinical trials of preventive tools, as well as provide
      definitions that may improve the precision of measurement of the burden of
      disease.

PMID- 19383128
TI  - Detection and characterization of 3D-signature phosphorylation site motifs and
      their contribution towards improved phosphorylation site prediction in proteins.
AB  - BACKGROUND: Phosphorylation of proteins plays a crucial role in the regulation
      and activation of metabolic and signaling pathways and constitutes an important
      target for pharmaceutical intervention. Central to the phosphorylation process is
      the recognition of specific target sites by protein kinases followed by the
      covalent attachment of phosphate groups to the amino acids serine, threonine, or
      tyrosine. The experimental identification as well as computational prediction of
      phosphorylation sites (P-sites) has proved to be a challenging problem.
      Computational methods have focused primarily on extracting predictive features
      from the local, one-dimensional sequence information surrounding phosphorylation
      sites. RESULTS: We characterized the spatial context of phosphorylation sites and
      assessed its usability for improved phosphorylation site predictions. We
      identified 750 non-redundant, experimentally verified sites with three
      dimensional (3D) structural information available in the protein data bank (PDB)
      and grouped them according to their respective kinase family. We studied the
      spatial distribution of amino acids around phosphorserines, phosphothreonines,
      and phosphotyrosines to extract signature 3D-profiles. Characteristic spatial
      distributions of amino acid residue types around phosphorylation sites were
      indeed discernable, especially when kinase-family-specific target sites were
      analyzed. To test the added value of using spatial information for the
      computational prediction of phosphorylation sites, Support Vector Machines were
      applied using both sequence as well as structural information. When compared to
      sequence-only based prediction methods, a small but consistent performance
      improvement was obtained when the prediction was informed by 3D-context
      information. CONCLUSION: While local one-dimensional amino acid sequence
      information was observed to harbor most of the discriminatory power, spatial
      context information was identified as relevant for the recognition of kinases and
      their cognate target sites and can be used for an improved prediction of
      phosphorylation sites. A web-based service (Phos3D) implementing the developed
      structure-based P-site prediction method has been made available at
      (http://phos3d.mpimp-golm.mpg.de).

PMID- 19383127
TI  - Profile analysis and prediction of tissue-specific CpG island methylation
      classes.
AB  - BACKGROUND: The computational prediction of DNA methylation has become an
      important topic in the recent years due to its role in the epigenetic control of
      normal and cancer-related processes. While previous prediction approaches focused
      merely on differences between methylated and unmethylated DNA sequences, recent
      experimental results have shown the presence of much more complex patterns of
      methylation across tissues and time in the human genome. These patterns are only
      partially described by a binary model of DNA methylation. In this work we propose
      a novel approach, based on profile analysis of tissue-specific methylation that
      uncovers significant differences in the sequences of CpG islands (CGIs) that
      predispose them to a tissue- specific methylation pattern. RESULTS: We defined
      CGI methylation profiles that separate not only between constitutively methylated
      and unmethylated CGIs, but also identify CGIs showing a differential degree of
      methylation across tissues and cell-types or a lack of methylation exclusively in
      sperm. These profiles are clearly distinguished by a number of CGI attributes
      including their evolutionary conservation, their significance, as well as the
      evolutionary evidence of prior methylation. Additionally, we assess profile
      functionality with respect to the different compartments of protein coding genes
      and their possible use in the prediction of DNA methylation. CONCLUSION: Our
      approach provides new insights into the biological features that determine if a
      CGI has a functional role in the epigenetic control of gene expression and the
      features associated with CGI methylation susceptibility. Moreover, we show that
      the ability to predict CGI methylation is based primarily on the quality of the
      biological information used and the relationships uncovered between different
      sources of knowledge. The strategy presented here is able to predict, besides the
      constitutively methylated and unmethylated classes, two more tissue specific
      methylation classes conserving the accuracy provided by leading binary
      methylation classification methods.

PMID- 19383129
TI  - No evidence for protective erythropoietin alpha signalling in rat hepatocytes.
AB  - BACKGROUND: Recombinant human erythropoietin alpha (rHu-EPO) has been reported to
      protect the liver of rats and mice from ischemia-reperfusion injury. However,
      direct protective effects of rHu-EPO on hepatocytes and the responsible
      signalling pathways have not yet been described. The aim of the present work was
      to study the protective effect of rHu-EPO on warm hypoxia-reoxygenation and cold
      induced injury to hepatocytes and the rHu-EPO-dependent signalling involved.
      METHODS: Loss of viability of isolated rat hepatocytes subjected to
      hypoxia/reoxygenation or incubated at 4 degrees C followed by rewarming was
      determined from released lactate dehydrogenase activity in the absence and
      presence of rHu-EPO (0.2-100 U/ml). Apoptotic nuclear morphology was assessed by
      fluorescence microscopy using the nuclear fluorophores H33342 and propidium
      iodide. Erythropoietin receptor (EPOR), EPO and Bcl-2 mRNAs were quantified by
      real time PCR. Activation of JAK-2, STAT-3 and STAT-5 in hepatocytes and rat
      livers perfused in situ was assessed by Western blotting. RESULTS: In contrast to
      previous in vivo studies on ischemia-reperfusion injury to the liver, rHu-EPO was
      without any protective effect on hypoxic injury, hypoxia-reoxygenation injury and
      cold-induced apoptosis to isolated cultured rat hepatocytes. EPOR mRNA was
      identified in these cells but specific detection of the EPO receptor protein was
      not possible due to the lack of antibody specificity. Both, in the cultured rat
      hepatocytes (10 U/ml for 15 minutes) and in the rat liver perfused in situ with
      rHu-EPO (8.9 U/ml for 15 minutes) no evidence for EPO-dependent signalling was
      found as indicated by missing effects of rHu-EPO on phosphorylation of JAK-2,
      STAT-3 and STAT-5 and on the induction of Bcl-2 mRNA. CONCLUSION: Together, these
      results indicate the absence of any protective EPO signalling in rat hepatocytes.
      This implies that the protection provided by rHu-EPO in vivo against ischemia
      reperfusion and other causes of liver injury is most likely indirect and does not
      result from a direct effect on hepatocytes.

PMID- 19383130
TI  - Regulation of cellular proliferation, differentiation and cell death by activated
      Raf.
AB  - The protein kinases Raf-1, A-Raf and B-Raf connect receptor stimulation with
      intracellular signaling pathways and function as a central intermediate in many
      signaling pathways. Gain-of-function experiments shed light on the pleiotropic
      biological activities of these enzymes. Expression experiments involving
      constitutively active Raf revealed the essential functions of Raf in controlling
      proliferation, differentiation and cell death in a cell-type specific manner.

PMID- 19383131
TI  - Homolactic fermentation from glucose and cellobiose using Bacillus subtilis.
AB  - BACKGROUNG: Biodegradable plastics can be made from polylactate, which is a
      polymer made from lactic acid. This compound can be produced from renewable
      resources as substrates using microorganisms. Bacillus subtilis is a Gram
      positive bacterium recognized as a GRAS microorganism (generally regarded as
      safe) by the FDA. B. subtilis produces and secretes different kind of enzymes,
      such as proteases, cellulases, xylanases and amylases to utilize carbon sources
      more complex than the monosaccharides present in the environment. Thus, B.
      subtilis could be potentially used to hydrolyze carbohydrate polymers contained
      in lignocellulosic biomass to produce chemical commodities. Enzymatic hydrolysis
      of the cellulosic fraction of agroindustrial wastes produces cellobiose and a
      lower amount of glucose. Under aerobic conditions, B. subtilis grows using
      cellobiose as substrate. RESULTS: In this study, we proved that under non-aerated
      conditions, B. subtilis ferments cellobiose to produce L-lactate with 82% of the
      theoretical yield, and with a specific rate of L-lactate production similar to
      that one obtained fermenting glucose. Under fermentative conditions in a complex
      media supplemented with glucose, B. subtilis produces L-lactate and a low amount
      of 2,3-butanediol. To increase the L-lactate production of this organism, we
      generated the B subtilis CH1 alsS- strain that lacks the ability to synthesize
      2,3-butanediol. Inactivation of this pathway, that competed for pyruvate
      availability, let a 15% increase in L-lactate yield from glucose compared with
      the parental strain. CH1 alsS- fermented 5 and 10% of glucose to completion in
      mineral medium supplemented with yeast extract in four and nine days,
      respectively. CH1 alsS- produced 105 g/L of L-lactate in this last medium
      supplemented with 10% of glucose. The L-lactate yield was up to 95% using mineral
      media, and the optical purity of L-lactate was of 99.5% since B. subtilis has
      only one gene (lctE) that exclusively encodes a L-lactate deshydrogenase.
      CONCLUSION: This study shows that by taking advantage of the cellobiose
      utilization capability and osmotic stress high resistance of B. subtilis, a
      robust process for L-lactate production can be developed.

PMID- 19383132
TI  - Healthcare professionals and managers' participation in developing an
      intervention: a pre-intervention study in the elderly care context.
AB  - BACKGROUND: In order to increase the chances of success in new interventions in
      healthcare, it is generally recommended to tailor the intervention to the target
      setting and the target professionals. Nonetheless, pre-intervention studies are
      rarely conducted or are very limited in scope. Moreover, little is known about
      how to integrate the results of a pre-intervention study into an intervention. As
      part of a project to develop an intervention aimed at improving care for the
      elderly in France, a pre-intervention study was conducted to systematically
      gather data on the current practices, issues, and expectations of healthcare
      professionals and managers in order to determine the defining features of a
      successful intervention. METHODS: A qualitative study was carried out from 2004
      to 2006 using a grounded theory approach and involving a purposeful sample of 56
      healthcare professionals and managers in Paris, France. Four sources of evidence
      were used: interviews, focus groups, observation, and documentation. RESULTS: The
      stepwise approach comprised three phases, and each provided specific results. In
      the first step of the pre-intervention study, we gathered data on practices,
      perceived issues, and expectations of healthcare professionals and managers. The
      second step involved holding focus groups in order to define the characteristics
      of a tailor-made intervention. The third step allowed validation of the findings.
      Using this approach, we were able to design and develop an intervention in
      elderly care that met the professionals' and managers' expectations. CONCLUSION:
      This article reports on an in-depth pre-intervention study that led to the design
      and development of an intervention in partnership with local healthcare
      professionals and managers. The stepwise approach represents an innovative
      strategy for developing tailored interventions, particularly in complex domains
      such as chronic care. It highlights the usefulness of seeking out the insight of
      healthcare professionalnd managers and emphasizes the need to intervene at
      different levels. Further research will be needed in order to develop a more
      thorough understanding of the impacts of such strategies on the final outcomes of
      intervention implementations.

PMID- 19383133
TI  - Utilization of the ART approach in a group of public oral health operators in
      South Africa: a 5-year longitudinal study.
AB  - BACKGROUND: A significant increase in the proportion of restorations to the
      number of tooth extractions was reported after the introduction of ART in an
      academic mobile dental service in South Africa. The changes were ascribed to its
      less threatening procedure. Based on these findings, ART was subsequently
      introduced into the public oral health service of Ekurhuleni district in the
      South African province of Gauteng. This article reports on the 5-year restorative
      treatment pattern of operators in the Ekurhuleni district, who adopted the ART
      approach into their daily dental practice. METHODS: Of the 21 trained operators,
      11 had placed more than 10% of restorations using ART at year 1 and were
      evaluated after 5 years. Data, including number of restored and extracted teeth
      and type of restoration, were drawn from clinical records 4 months before, and up
      to 5 years after training. The restoration/extraction ratio (REX score) and the
      proportion of ART restorations to the total number of restorations were
      calculated. The paired sample t-test and linear regression analysis were applied.
      RESULTS: The mean percentage of ART restorations after 1 year was 24.0% (SE 7.2)
      and significantly increased annually to 42.7% (SE 9.2) after 5 years in permanent
      dentitions. In primary dentitions the mean percentage of ART restorations after 1
      year was 80.6% (SE 4.9) and 72.6% (SE 8.8) after 5 years. The mean REX score
      before ART training was 0.08 (SE 0.03) and 0.07 (SE 0.04) for permanent and
      primary teeth, respectively and 0.11 (SE 0.03) and 0.17 (SE 0.05) after 5 years.
      CONCLUSION: Five years after training, ART had been used consistently in this
      selected group of operators as the predominant restorative treatment used for
      primary teeth and showed a significant annual increase in permanent teeth.
      However, this change had not resulted in an increase in the REX score in both
      dentitions.

PMID- 19383135
TI  - A strain-variable bacteriocin in Bacillus anthracis and Bacillus cereus with
      repeated Cys-Xaa-Xaa motifs.
AB  - Bacteriocins are peptide antibiotics from ribosomally translated precursors,
      produced by bacteria often through extensive post-translational modification.
      Minimal sequence conservation, short gene lengths, and low complexity sequence
      can hinder bacteriocin identification, even during gene calling, so they are
      often discovered by proximity to accessory genes encoding maturation, immunity,
      and export functions. This work reports a new subfamily of putative thiazole
      containing heterocyclic bacteriocins. It appears universal in all strains of
      Bacillus anthracis and B. cereus, but has gone unrecognized because it is always
      encoded far from its maturation protein operon. Patterns of insertions and
      deletions among twenty-four variants suggest a repeating functional unit of Cys
      Xaa-Xaa.

PMID- 19383136
TI  - Ethnic differences in BMI among Dutch adolescents: what is the role of screen
      viewing, active commuting to school, and consumption of soft drinks and high
      caloric snacks?
AB  - BACKGROUND: The threats posed by the rising prevalence of overweight and obesity
      on public health have been widely acknowledged. Several population groups, which
      deserve special attention because of their higher prevalence rates, have been
      identified. These include adolescents and ethnic sub-groups. The aim of the
      present study was twofold: (1) to assess ethnic differences in body mass index
      (BMI) and in behaviours that are related to both energy intake and energy
      expenditure, and (2) to examine whether these behaviours explain the relationship
      between ethnicity and BMI. METHODS: We conducted a cross-sectional data analysis
      among 957 Dutch adolescents (mean age = 12.7 years). Body height and weight were
      measured using a standardized protocol. Adolescents completed a questionnaire on
      screen-viewing behaviour, physical activity, consumption of sugar-containing
      beverages, and consumption of high-caloric snacks. RESULTS: In our study sample
      121 adolescents (= 13%) were of Non-Western origin. BMI was significantly higher
      in Non-Western adolescents (boys: 19.9 kg/m2, SD = 3.0, girls: 20.9 kg/m2, SD =
      3.8) compared to Dutch adolescents (boys: 18.4 kg/m2, SD = 2.8, girls: 19.0
      kg/m2, SD = 3.0). Our results show that time spent on television viewing, active
      commuting to school, and consumption of fruit juices partially mediated the
      association between BMI and ethnicity. CONCLUSION: Behaviours related to both
      energy expenditure and energy intake may contribute to the ethnic differences in
      BMI in adolescents and should be considered when tailoring overweight prevention
      programs to ethnic subpopulations. TRIAL REGISTRATION: International Standard
      Randomised Controlled Trial Number ISRCTN87127361.

PMID- 19383134
TI  - Clinical evaluation study of the German network of disorders of sex development
      (DSD)/intersexuality: study design, description of the study population, and data
      quality.
AB  - BACKGROUND: The German Network of Disorders of Sex Development
      (DSD)/Intersexuality carried out a large scale clinical evaluation study on
      quality of life, gender identity, treatment satisfaction, coping, and problems
      associated with diagnoses and therapies in individuals with disorders of sex
      development (DSD). DSD are a heterogeneous group of various genetic disorders of
      sex determination or sex differentiation, all of which are rare conditions. In
      about half of all cases the molecular genetic diagnosis is unknown and diagnosis
      rests on clinical features. METHODS AND DESIGN: The multi-centre clinical
      evaluation study includes short-term follow-up in some and cross-sectional
      assessments in all age and diagnostic groups fitting the criteria of DSD.
      Recruitment was from January 2005 until December 2007 in whole Germany and,
      additionally, in 2007 in Austria and German-speaking Switzerland. The study
      consists of a psychosocial inquiry for children, adolescents and their parents,
      and adults with standardized instruments and the collection of DSD-specific
      medical data by the attending physician. The main goal was the description of
      clinical outcomes and the health-care situation of individuals with DSD using a
      broad generic definition of DSD including all conditions with a mismatch of
      chromosomal, gonadal and phenotypical sex. 439 children and adolescents, their
      parents and adults with DSD participated. DISCUSSION: The clinical evaluation
      study represents the most comprehensive study in this clinical field. The paper
      discusses the study protocol, the data management and data quality as well as the
      classification used, and it describes the study population. Given the lack of
      large datasets in rare conditions such as DSD and often biased results from small
      scale clinical case series, the study aims to generate concrete hypotheses for
      evidence-based guidelines, which should be tested in further studies.

PMID- 19383137
TI  - ACID: annotation of cassette and integron data.
AB  - BACKGROUND: Although integrons and their associated gene cassettes are present in
      ~10% of bacteria and can represent up to 3% of the genome in which they are
      found, very few have been properly identified and annotated in public databases.
      These genetic elements have been overlooked in comparison to other vectors that
      facilitate lateral gene transfer between microorganisms. DESCRIPTION: By
      automating the identification of integron integrase genes and of the non-coding
      cassette-associated attC recombination sites, we were able to assemble a database
      containing all publicly available sequence information regarding these genetic
      elements. Specialists manually curated the database and this information was used
      to improve the automated detection and annotation of integrons and their encoded
      gene cassettes. ACID (annotation of cassette and integron data) can be searched
      using a range of queries and the data can be downloaded in a number of formats.
      Users can readily annotate their own data and integrate it into ACID using the
      tools provided. CONCLUSION: ACID is a community resource providing easy access to
      annotations of integrons and making tools available to detect them in novel
      sequence data. ACID also hosts a forum to prompt integron-related discussion,
      which can hopefully lead to a more universal definition of this genetic element.

PMID- 19383138
TI  - Syndromic surveillance: STL for modeling, visualizing, and monitoring disease
      counts.
AB  - BACKGROUND: Public health surveillance is the monitoring of data to detect and
      quantify unusual health events. Monitoring pre-diagnostic data, such as emergency
      department (ED) patient chief complaints, enables rapid detection of disease
      outbreaks. There are many sources of variation in such data; statistical methods
      need to accurately model them as a basis for timely and accurate disease outbreak
      methods. METHODS: Our new methods for modeling daily chief complaint counts are
      based on a seasonal-trend decomposition procedure based on loess (STL) and were
      developed using data from the 76 EDs of the Indiana surveillance program from
      2004 to 2008. Square root counts are decomposed into inter-annual, yearly
      seasonal, day-of-the-week, and random-error components. Using this decomposition
      method, we develop a new synoptic-scale (days to weeks) outbreak detection method
      and carry out a simulation study to compare detection performance to four well
      known methods for nine outbreak scenarios. RESULT: The components of the STL
      decomposition reveal insights into the variability of the Indiana ED data. Day-of
      the-week components tend to peak Sunday or Monday, fall steadily to a minimum
      Thursday or Friday, and then rise to the peak. Yearly-seasonal components show
      seasonal influenza, some with bimodal peaks.Some inter-annual components increase
      slightly due to increasing patient populations. A new outbreak detection method
      based on the decomposition modeling performs well with 90 days or more of data.
      Control limits were set empirically so that all methods had a specificity of 97%.
      STL had the largest sensitivity in all nine outbreak scenarios. The STL method
      also exhibited a well-behaved false positive rate when run on the data with no
      outbreaks injected. CONCLUSION: The STL decomposition method for chief complaint
      counts leads to a rapid and accurate detection method for disease outbreaks, and
      requires only 90 days of historical data to be put into operation. The
      visualization tools that accompany the decomposition and outbreak methods provide
      much insight into patterns in the data, which is useful for surveillance
      operations.

PMID- 19383139
TI  - A bag-of-words approach for Drosophila gene expression pattern annotation.
AB  - BACKGROUND: Drosophila gene expression pattern images document the spatiotemporal
      dynamics of gene expression during embryogenesis. A comparative analysis of these
      images could provide a fundamentally important way for studying the regulatory
      networks governing development. To facilitate pattern comparison and searching,
      groups of images in the Berkeley Drosophila Genome Project (BDGP) high-throughput
      study were annotated with a variable number of anatomical terms manually using a
      controlled vocabulary. Considering that the number of available images is rapidly
      increasing, it is imperative to design computational methods to automate this
      task. RESULTS: We present a computational method to annotate gene expression
      pattern images automatically. The proposed method uses the bag-of-words scheme to
      utilize the existing information on pattern annotation and annotates images using
      a model that exploits correlations among terms. The proposed method can annotate
      images individually or in groups (e.g., according to the developmental stage). In
      addition, the proposed method can integrate information from different two
      dimensional views of embryos. Results on embryonic patterns from BDGP data
      demonstrate that our method significantly outperforms other methods. CONCLUSION:
      The proposed bag-of-words scheme is effective in representing a set of
      annotations assigned to a group of images, and the model employed to annotate
      images successfully captures the correlations among different controlled
      vocabulary terms. The integration of existing annotation information from
      multiple embryonic views improves annotation performance.

PMID- 19383141
TI  - Chronic illness and multimorbidity among problem drug users: a comparative cross
      sectional pilot study in primary care.
AB  - BACKGROUND: Although multimorbidity has important implications for patient care
      in general practice, limited research has examined chronic illness and health
      service utilisation among problem drug users. This study aimed to determine
      chronic illness prevalence and health service utilisation among problem drug
      users attending primary care for methadone treatment, to compare these rates with
      matched 'controls' and to develop and pilot test a valid study instrument.
      METHODS: A cross-sectional study of patients attending three large urban general
      practices in Dublin, Ireland for methadone treatment was conducted, and this
      sample was compared with a control group matched by practice, age, gender and
      General Medical Services (GMS) status. RESULTS: Data were collected on 114
      patients. Fifty-seven patients were on methadone treatment, of whom 52(91%) had
      at least one chronic illness (other then substance use) and 39(68%) were
      prescribed at least one regular medication. Frequent utilisation of primary care
      services and secondary care services in the previous six months was observed
      among patients on methadone treatment and controls, although the former had
      significantly higher chronic illness prevalence and primary care contact rates.
      The study instrument facilitated data collection that was feasible and with
      minimal inter-observer variation. CONCLUSION: Multimorbidity is common among
      problem drug users attending general practice for methadone treatment. Primary
      care may therefore have an important role in primary and secondary prevention of
      chronic illnesses among this population. This study offers a feasible study
      instrument for further work on this issue. (238 words).

PMID- 19383140
TI  - Small molecule inhibitors of the Yersinia type III secretion system impair the
      development of Chlamydia after entry into host cells.
AB  - BACKGROUND: Chlamydiae are obligate intracellular pathogens that possess a type
      III secretion system to deliver proteins into the host cell during infection.
      Small molecule inhibitors of type III secretion in Yersinia, termed INPs (Innate
      Pharmaceuticals AB) were reported to strongly inhibit Chlamydia growth in
      epithelial cells. In this study we have analyzed the effect of these drugs on
      bacterial invasiveness. RESULTS: We demonstrate that INPs affect Chlamydia growth
      in a dose dependent manner after bacterial invasion. The efficiency of C.
      trachomatis L2 and C. caviae GPIC entry into host cells was not altered in the
      presence of INPs. In C. caviae, entry appears to proceed normally with
      recruitment of actin and the small GTPases Rac, Cdc42 and Arf6 to the site of
      bacterial entry. CONCLUSION: INPs have a strong inhibitory effect on Chlamydia
      growth. However, bacterial invasion is not altered in the presence of these
      drugs. In the light of these results, we discuss several hypotheses regarding the
      mode of action of INPs on type III secretion during the Chlamydia infectious
      cycle.

PMID- 19383142
TI  - Gene composer: database software for protein construct design, codon engineering,
      and gene synthesis.
AB  - BACKGROUND: To improve efficiency in high throughput protein structure
      determination, we have developed a database software package, Gene Composer,
      which facilitates the information-rich design of protein constructs and their
      codon engineered synthetic gene sequences. With its modular workflow design and
      numerous graphical user interfaces, Gene Composer enables researchers to perform
      all common bio-informatics steps used in modern structure guided protein
      engineering and synthetic gene engineering. RESULTS: An interactive Alignment
      Viewer allows the researcher to simultaneously visualize sequence conservation in
      the context of known protein secondary structure, ligand contacts, water
      contacts, crystal contacts, B-factors, solvent accessible area, residue property
      type and several other useful property views. The Construct Design Module enables
      the facile design of novel protein constructs with altered N- and C-termini,
      internal insertions or deletions, point mutations, and desired affinity tags. The
      modifications can be combined and permuted into multiple protein constructs, and
      then virtually cloned in silico into defined expression vectors. The Gene Design
      Module uses a protein-to-gene algorithm that automates the back-translation of a
      protein amino acid sequence into a codon engineered nucleic acid gene sequence
      according to a selected codon usage table with minimal codon usage threshold,
      defined G:C% content, and desired sequence features achieved through synonymous
      codon selection that is optimized for the intended expression system. The gene-to
      oligo algorithm of the Gene Design Module plans out all of the required
      overlapping oligonucleotides and mutagenic primers needed to synthesize the
      desired gene constructs by PCR, and for physically cloning them into selected
      vectors by the most popular subcloning strategies. CONCLUSION: We present a
      complete description of Gene Composer functionality, and an efficient PCR-based
      synthetic gene assembly procedure with mis-match specific endonuclease error
      correction in combination with PIPE cloning. In a sister manuscript we present
      data on how Gene Composer designed genes and protein constructs can result in
      improved protein production for structural studies.

PMID- 19383143
TI  - Combined protein construct and synthetic gene engineering for heterologous
      protein expression and crystallization using Gene Composer.
AB  - BACKGROUND: With the goal of improving yield and success rates of heterologous
      protein production for structural studies we have developed the database and
      algorithm software package Gene Composer. This freely available electronic tool
      facilitates the information-rich design of protein constructs and their
      engineered synthetic gene sequences, as detailed in the accompanying manuscript.
      RESULTS: In this report, we compare heterologous protein expression levels from
      native sequences to that of codon engineered synthetic gene constructs designed
      by Gene Composer. A test set of proteins including a human kinase (P38alpha),
      viral polymerase (HCV NS5B), and bacterial structural protein (FtsZ) were
      expressed in both E. coli and a cell-free wheat germ translation system. We also
      compare the protein expression levels in E. coli for a set of 11 different
      proteins with greatly varied G:C content and codon bias. CONCLUSION: The results
      consistently demonstrate that protein yields from codon engineered Gene Composer
      designs are as good as or better than those achieved from the synonymous native
      genes. Moreover, structure guided N- and C-terminal deletion constructs designed
      with the aid of Gene Composer can lead to greater success in gene to structure
      work as exemplified by the X-ray crystallographic structure determination of FtsZ
      from Bacillus subtilis. These results validate the Gene Composer algorithms, and
      suggest that using a combination of synthetic gene and protein construct
      engineering tools can improve the economics of gene to structure research.

PMID- 19383144
TI  - The gamma-gliadin multigene family in common wheat (Triticum aestivum) and its
      closely related species.
AB  - BACKGROUND: The unique properties of wheat flour primarily depend on gluten,
      which is the most important source of protein for human being. gamma-Gliadins
      have been considered to be the most ancient of the wheat gluten family. The
      complex family structure of gamma-gliadins complicates the determination of their
      function. Moreover, gamma-gliadins contain several sets of celiac disease
      epitopes. However, no systematic research has been conducted yet. RESULTS: A
      total of 170 gamma-gliadin genes were isolated from common wheat and its closely
      related species, among which 138 sequences are putatively functional. The ORF
      lengths of these sequences range from 678 to 1089 bp, and the repetitive region
      is mainly responsible for the size heterogeneity of gamma-gliadins. The repeat
      motif P(Q/L/S/T/I/V/R/A)F(S/Y/V/Q/I/C/L)P(R/L/S/T/H/C/Y)Q1-2(P(S/L/T/A/F/H)QQ)1
      2is repeated from 7 to 22 times. Sequence polymorphism and linkage disequilibrium
      analyses show that gamma-gliadins are highly diverse. Phylogenic analyses
      indicate that there is no obvious discrimination between Sitopsis and Ae.
      tauschii at the Gli-1 loci, compared with diploid wheat. According to the number
      and placement of cysteine residues, we defined nine cysteine patterns and 17
      subgroups. Alternatively, we classified gamma-gliadins into two types based on
      the length of repetitive domain. Amino acid composition analyses indicate that
      there is a wide range of essential amino acids in gamma-gliadins, and those gamma
      gliadins from subgroup SG-10 and SG-12 and gamma-gliadins with a short repetitive
      domain are more nutritional. A screening of toxic epitopes shows that gamma
      gliadins with a pattern of C9 and gamma-gliadins with a short repetitive domain
      almost lack any epitopes. CONCLUSION: gamma-Gliadin sequences in wheat and
      closely related Aegilops species are diverse. Each group/subgroup contributes
      differently to nutritional quality and epitope content. It is suggested that the
      genes with a short repetitive domain are more nutritional and valuable.
      Therefore, it is possible to breed wheat varieties, the gamma-gliadins of which
      are less, even non-toxic and more nutritional.

PMID- 19383145
TI  - Population norms and cut-off-points for suboptimal health related quality of life
      in two generic measures for adolescents: the Spanish VSP-A and KINDL-R.
AB  - BACKGROUND: Health-related quality of life (HRQL) outcome measures are complex
      and for further application in clinical practice and health service research the
      meaning of their scorings should be studied in depth. The aim of this study was
      to increase the interpretability of the Spanish VSP-A and KINDL-R scores.
      METHODS: A representative sample of adolescents aged 12 to 18 years old was
      selected in Spain. The Spanish VSP-A and KINDL-R, two generic HRQL measures
      (range: 0-100), were self-administered along with other external anchor measures
      (Strengths and Difficulties Questionnaire, Oslo Social Support Scale and self
      declaration of chronic conditions) and sent by post. Percentiles of both HRQL
      questionnaires were obtained by gender, and age group and effect sizes (ES) were
      calculated. Receiver Operating Characteristic curves and related sensitivity (SE)
      and specificity (SP) values were also computed. RESULTS: The Spanish VSP-A and
      KINDL-R were completed by 555 adolescents. A moderate ES was shown in
      Psychological well-being between younger and older girls (ES: 0.77) in the VSP-A
      and small ES in the KINDL (ES: 0.41) between these groups. A SE and SP value
      close to 0.70 was associated to a global HRQL score of 65 in the VSP-A and 70 in
      the KINDL-R, when compared to anchors measuring mental and psychosocial health.
      Adolescents with scores bellow these cut-off points showed a moderate probability
      of presenting more impairment in their HRQL. CONCLUSION: The results of this
      study will be of help to interpret the VSP-A AND KINDL-R questionnaires by
      comparing with the general population and also provide cut-off points to define
      adolescents with health problems.

PMID- 19383146
TI  - Acclimatory responses of the Daphnia pulex proteome to environmental changes. I.
      Chronic exposure to hypoxia affects the oxygen transport system and carbohydrate
      metabolism.
AB  - BACKGROUND: Freshwater planktonic crustaceans of the genus Daphnia show a
      remarkable plasticity to cope with environmental changes in oxygen concentration
      and temperature. One of the key proteins of adaptive gene control in Daphnia
      pulex under hypoxia is hemoglobin (Hb), which increases in hemolymph
      concentration by an order of magnitude and shows an enhanced oxygen affinity due
      to changes in subunit composition. To explore the full spectrum of adaptive
      protein expression in response to low-oxygen conditions, two-dimensional gel
      electrophoresis and mass spectrometry were used to analyze the proteome
      composition of animals acclimated to normoxia (oxygen partial pressure [Po2]: 20
      kPa) and hypoxia (Po2: 3 kPa), respectively. RESULTS: The comparative proteome
      analysis showed an up-regulation of more than 50 protein spots under hypoxia.
      Identification of a major share of these spots revealed acclimatory changes for
      Hb, glycolytic enzymes (enolase), and enzymes involved in the degradation of
      storage and structural carbohydrates (e.g. cellubiohydrolase). Proteolytic
      enzymes remained constitutively expressed on a high level. CONCLUSION:
      Acclimatory adjustments of the D. pulex proteome to hypoxia included a strong
      induction of Hb and carbohydrate-degrading enzymes. The scenario of adaptive
      protein expression under environmental hypoxia can be interpreted as a process to
      improve oxygen transport and carbohydrate provision for the maintenance of ATP
      production, even during short episodes of tissue hypoxia requiring support from
      anaerobic metabolism.

PMID- 19383147
TI  - Acclimatory responses of the Daphnia pulex proteome to environmental changes. II.
      Chronic exposure to different temperatures (10 and 20 degrees C) mainly affects
      protein metabolism.
AB  - BACKGROUND: Temperature affects essentially every aspect of the biology of
      poikilothermic animals including the energy and mass budgets, activity, growth,
      and reproduction. While thermal effects in ecologically important groups such as
      daphnids have been intensively studied at the ecosystem level and at least partly
      at the organismic level, much less is known about the molecular mechanisms
      underlying the acclimation to different temperatures. By using 2D gel
      electrophoresis and mass spectrometry, the present study identified the major
      elements of the temperature-induced subset of the proteome from differently
      acclimated Daphnia pulex. RESULTS: Specific sets of proteins were found to be
      differentially expressed in 10 degrees C or 20 degrees C acclimated D. pulex.
      Most cold-repressed proteins comprised secretory enzymes which are involved in
      protein digestion (trypsins, chymotrypsins, astacin, carboxypeptidases). The cold
      induced sets of proteins included several vitellogenin and actin isoforms
      (cytoplasmic and muscle-specific), and an AAA+ ATPase. Carbohydrate-modifying
      enzymes were constitutively expressed or down-regulated in the cold. CONCLUSION:
      Specific sets of cold-repressed and cold-induced proteins in D. pulex can be
      related to changes in the cellular demand for amino acids or to the compensatory
      control of physiological processes. The increase of proteolytic enzyme
      concentration and the decrease of vitellogenin, actin and total protein
      concentration between 10 degrees C and 20 degrees C acclimated animals reflect
      the increased amino-acids demand and the reduced protein reserves in the animal's
      body. Conversely, the increase of actin concentration in cold-acclimated animals
      may contribute to a compensatory mechanism which ensures the relative constancy
      of muscular performance. The sheer number of peptidase genes (serine-peptidase
      like: > 200, astacin-like: 36, carboxypeptidase-like: 30) in the D. pulex genome
      suggests large-scaled gene family expansions that might reflect specific
      adaptations to the lifestyle of a planktonic filter feeder in a highly variable
      aquatic environment.

PMID- 19383148
TI  - Physiological responses of Daphnia pulex to acid stress.
AB  - BACKGROUND: Acidity exerts a determining influence on the composition and
      diversity of freshwater faunas. While the physiological implications of
      freshwater acidification have been intensively studied in teleost fish and
      crayfish, much less is known about the acid-stress physiology of ecologically
      important groups such as cladoceran zooplankton. This study analyzed the
      extracellular acid-base state and CO2 partial pressure (P(CO2)), circulation and
      ventilation, as well as the respiration rate of Daphnia pulex acclimated to
      acidic (pH 5.5 and 6.0) and circumneutral (pH 7.8) conditions. RESULTS: D. pulex
      had a remarkably high extracellular pH of 8.33 and extracellular P(CO2) of 0.56
      kPa under normal ambient conditions (pH 7.8 and normocapnia). The hemolymph had a
      high bicarbonate concentration of 20.9 mM and a total buffer value of 51.5 meq L(
      1) pH(-1). Bicarbonate covered 93% of the total buffer value. Acidic conditions
      induced a slight acidosis (DeltapH = 0.16-0.23), a 30-65% bicarbonate loss, and
      elevated systemic activities (tachycardia, hyperventilation, hypermetabolism). pH
      6.0 animals partly compensated the bicarbonate loss by increasing the non
      bicarbonate buffer value from 2.0 to 5.1 meq L(-1) pH(-1). The extracellular
      P(CO2) of pH 5.5 animals was significantly reduced to 0.33 kPa, and these animals
      showed the highest tolerance to a short-term exposure to severe acid stress.
      CONCLUSION: Chronic exposure to acidic conditions had a pervasive impact on
      Daphnia's physiology including acid-base balance, extracellular PCO2, circulation
      and ventilation, and energy metabolism. Compensatory changes in extracellular non
      bicarbonate buffering capacity and the improved tolerance to severe acid stress
      indicated the activation of defense mechanisms which may result from gene
      expression mediated adjustments in hemolymph buffer proteins and in epithelial
      properties. Mechanistic analyses of the interdependence between extracellular
      acid-base balance and CO2 transport raised the question of whether a carbonic
      anhydrase (CA) is involved in the catalysis of the CO2-HCO3(-)-H(+) reaction,
      which led to the discovery of 31 CA-genes in the genome of D. pulex.

PMID- 19383149
TI  - Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors.
AB  - BACKGROUND: TRPA1 has been implicated in both chemo- and mechanosensation. Recent
      work demonstrates that inhibiting TRPA1 function reduces mechanical
      hypersensitivity produced by inflammation. Furthermore, a broad range of chemical
      irritants require functional TRPA1 to exert their effects. In this study we use
      the ex-vivo skin-nerve preparation to directly determine the contribution of
      TRPA1 to mechanical- and chemical-evoked responses at the level of the primary
      afferent terminal. RESULTS: Acute application of HC-030031, a selective TRPA1
      antagonist, inhibited all formalin responses in rat C fibers but had no effect on
      TRPV1 function, assessed by capsaicin responsiveness. Genetic ablation
      experiments corroborated the pharmacological findings as C fibers from wild type
      mice responded to both formalin and capsaicin, but fibers from their TRPA1
      deficient littermates responded only to capsaicin. HC-030031 markedly reduced the
      mechanically-evoked action potential firing in rat and wild type mouse C fibers,
      particularly at high-intensity forces, but had no effect on the mechanical
      responsiveness of Adelta fiber nociceptors. Furthermore, HC-030031 had no effect
      on mechanically-evoked firing in C fibers from TRPA1-deficient mice, indicating
      that HC-030031 inhibits mechanically-evoked firing via a TRPA1-dependent
      mechanism. CONCLUSION: Our data show that acute pharmacological blockade of TRPA1
      at the cutaneous receptive field inhibits formalin-evoked activation and markedly
      reduces mechanically-evoked action potential firing in C fibers. Thus, functional
      TRPA1 at sensory afferent terminals in skin is required for their responsiveness
      to both noxious chemical and mechanical stimuli.

PMID- 19383150
TI  - The cytochrome P450 (CYP) gene superfamily in Daphnia pulex.
AB  - BACKGROUND: Cytochrome P450s (CYPs) in animals fall into two categories: those
      that synthesize or metabolize endogenous molecules and those that interact with
      exogenous chemicals from the diet or the environment. The latter form a critical
      component of detoxification systems. RESULTS: Data mining and manual curation of
      the Daphnia pulex genome identified 75 functional CYP genes, and three CYP
      pseudogenes. These CYPs belong to 4 clans, 13 families, and 19 subfamilies. The
      CYP 2, 3, 4, and mitochondrial clans are the same four clans found in other
      sequenced protostome genomes. Comparison of the CYPs from D. pulex to the CYPs
      from insects, vertebrates and sea anemone (Nematostella vectensis) show that the
      CYP2 clan, and to a lesser degree, the CYP4 clan has expanded in Daphnia pulex,
      whereas the CYP3 clan has expanded in insects. However, the expansion of the
      Daphnia CYP2 clan is not as great as the expansion observed in deuterostomes and
      the nematode C. elegans. Mapping of CYP tandem repeat regions demonstrated the
      unusual expansion of the CYP370 family of the CYP2 clan. The CYP370s are similar
      to the CYP15s and CYP303s that occur as solo genes in insects, but the CYP370s
      constitute approximately 20% of all the CYP genes in Daphnia pulex. Lastly, our
      phylogenetic comparisons provide new insights into the potential origins of
      otherwise mysterious CYPs such as CYP46 and CYP19 (aromatase). CONCLUSION:
      Overall, the cladoceran, D. pulex has a wide range of CYPs with the same clans as
      insects and nematodes, but with distinct changes in the size and composition of
      each clan.

PMID- 19383151
TI  - The ABC transporter gene family of Daphnia pulex.
AB  - BACKGROUND: The large gene superfamily of ABC (ATP-binding cassette) transporters
      encodes membrane proteins involved in trafficking processes across biological
      membranes and further essential cell biological functions. ABC transporters are
      evolutionary ancient and involved in the biochemical defence against toxicants.
      We report here a genome-wide survey of ABC proteins of Daphnia pulex, providing
      for the first time information on ABC proteins in crustacea, a primarily aquatic
      arthropod subphylum of high ecological and economical importance. RESULTS: We
      identified 64 ABC proteins in the Daphnia genome, which possesses members of all
      current ABC subfamilies A to H. To unravel phylogenetic relationships, ABC
      proteins of Daphnia were compared to those from yeast, worm, fruit fly and human.
      A high conservation of Daphnia of ABC transporters was observed for proteins
      involved in fundamental cellular processes, including the mitochondrial half
      transporters of the ABCB subfamily, which function in iron metabolism and
      transport of Fe/S protein precursors, and the members of subfamilies ABCD, ABCE
      and ABCF, which have roles in very long chain fatty acid transport, initiation of
      gene transcription and protein translation, respectively. A number of Daphnia
      proteins showed one-to-one orthologous relationships to Drosophila ABC proteins
      including the sulfonyl urea receptor (SUR), the ecdysone transporter ET23, and
      the eye pigment precursor transporter scarlet. As the fruit fly, Daphnia lacked
      homologues to the TAP protein, which plays a role in antigene processing, and the
      cystic fibrosis transmembrane conductance regulator (CFTR), which functions as a
      chloride channel. Daphnia showed two proteins homologous to MDR (multidrug
      resistance) P-glycoproteins (ABCB subfamily) and six proteins homologous to MRPs
      (multidrug resistance-associated proteins) (ABCC subfamily). However, lineage
      specific gene duplications in the ABCB and ABCC subfamilies complicated the
      inference of function. A particularly high number of gene duplications were
      observed in the ABCG and ABCH subfamilies, which have 23 and 15 members,
      respectively. CONCLUSION: The in silico characterisation of ABC transporters in
      the Daphnia pulex genome revealed that the complement of ABC transporters is as
      complex in crustaceans as that other metazoans. Not surprisingly, among currently
      available genomes, Daphnia ABC transporters most closely resemble those of the
      fruit fly, another arthropod.

PMID- 19383153
TI  - LC-MS/MS-based proteome profiling in Daphnia pulex and Daphnia longicephala: the
      Daphnia pulex genome database as a key for high throughput proteomics in Daphnia.
AB  - BACKGROUND: Daphniids, commonly known as waterfleas, serve as important model
      systems for ecology, evolution and the environmental sciences. The sequencing and
      annotation of the Daphnia pulex genome both open future avenues of research on
      this model organism. As proteomics is not only essential to our understanding of
      cell function, and is also a powerful validation tool for predicted genes in
      genome annotation projects, a first proteomic dataset is presented in this
      article. RESULTS: A comprehensive set of 701,274 peptide tandem-mass-spectra,
      derived from Daphnia pulex, was generated, which lead to the identification of
      531 proteins. To measure the impact of the Daphnia pulex filtered models database
      for mass spectrometry based Daphnia protein identification, this result was
      compared with results obtained with the Swiss-Prot and the Drosophila
      melanogaster database. To further validate the utility of the Daphnia pulex
      database for research on other Daphnia species, additional 407,778 peptide tandem
      mass-spectra, obtained from Daphnia longicephala, were generated and evaluated,
      leading to the identification of 317 proteins. CONCLUSION: Peptides identified in
      our approach provide the first experimental evidence for the translation of a
      broad variety of predicted coding regions within the Daphnia genome. Furthermore
      it could be demonstrated that identification of Daphnia longicephala proteins
      using the Daphnia pulex protein database is feasible but shows a slightly reduced
      identification rate. Data provided in this article clearly demonstrates that the
      Daphnia genome database is the key for mass spectrometry based high throughput
      proteomics in Daphnia.

PMID- 19383152
TI  - O-GlcNAc modifications regulate cell survival and epiboly during zebrafish
      development.
AB  - BACKGROUND: The post-translational addition of the monosaccharide O-linked beta-N
      acetylglucosamine (O-GlcNAc) regulates the activity of a wide variety of nuclear
      and cytoplasmic proteins. The enzymes O-GlcNAc Transferase (Ogt) and O-GlcNAcase
      (Oga) catalyze, respectively, the attachment and removal of O-GlcNAc to target
      proteins. In adult mice, Ogt and Oga attenuate the response to insulin by
      modifying several components of the signal transduction pathway. Complete loss of
      ogt function, however, is lethal to mouse embryonic stem cells, suggesting that
      the enzyme has additional, unstudied roles in development. We have utilized
      zebrafish as a model to determine role of O-GlcNAc modifications in development.
      Zebrafish has two ogt genes, encoding six different enzymatic isoforms that are
      expressed maternally and zygotically. RESULTS: We manipulated O-GlcNAc levels in
      zebrafish embryos by overexpressing zebrafish ogt, human oga or by injecting
      morpholinos against ogt transcripts. Each of these treatments results in embryos
      with shortened body axes and reduced brains at 24 hpf. The embryos had 23% fewer
      cells than controls, and displayed increased rates of cell death as early as the
      mid-gastrula stages. An extensive marker analysis indicates that derivatives of
      three germ layers are reduced to variable extents, and the embryos are severely
      disorganized after gastrulation. Overexpression of Ogt and Oga delayed epiboly
      and caused a severe disorganization of the microtubule and actin based
      cytoskeleton in the extra-embryonic yolk syncytial layer (YSL). The cytoskeletal
      defects resemble those previously reported for embryos lacking function of the
      Pou5f1/Oct4 transcription factor spiel ohne grenzen. Consistent with this,
      Pou5f1/Oct4 is modified by O-GlcNAc in human embryonic stem cells. CONCLUSION: We
      conclude that O-GlcNAc modifications control the activity of proteins that
      regulate apoptosis and epiboly movements, but do not seem to regulate germ layer
      specification. O-GlcNAc modifies the transcription factor Spiel ohne
      grenzen/Pou5f1 and may regulate its activity.

PMID- 19383154
TI  - Aortic root surgery in septuagenarians: impact of different surgical techniques.
AB  - BACKGROUND: To evaluate the impact and safety of different surgical techniques
      for aortic root replacement (ARR) on early and late morbidity and mortality in
      septuagenarians undergoing ARR. METHODS: Ninety-five patients (73.8 +/- 3.2
      years) were operated and divided into three groups according to the aortic root
      procedure; MECH-group (n = 51) patients with a mechanical composite graft, BIO
      group (n = 22) patients with a customized biological composite graft, and REIMPL
      group (n = 22) patients with a valve sparing aortic root reimplantation (David
      I). In 42.1% (40/95) of these patients the aortic arch was replaced. Follow-up
      was completed in 95.2% (79/83) of in-hospital survivors. RESULTS: Hospital
      mortality was 12.6% (12/95) in the entire population (MECH. 15.7% (8/51), BIO
      19.7% (4/22), REIMPL 0% (0/22); p = 0.004). Two patients died intraoperatively.
      The most frequent postoperative complications were prolonged mechanical
      ventilation ((>48 h) in 16.8% (16/93) (MECH. 7% (7/51), BIO 36.4% (8/22), REIMPL
      4.5% (1/22); p = 0.013) and rethoracotomy for postoperative bleeding in 12.6%
      (12/95) (MECH. 12% (6/51), BIO 22.7% (5/22), REIMPL 4.5% (1/22); p = 0.19).
      Nineteen late deaths (22.9%) (19/83) (MECH 34.8% (15/43), BIO 16.7% (3/18),
      REIMPL 4.5% (1/22); p = 0.012) occurred during a mean follow-up of 41 +/- 42
      months (MECH 48 +/- 48 months, BIO 25 +/- 37 months, REIMPL 40 +/- 28 months, p =
      0.028). Postoperative NYHA class decreased significantly (p = 0.017) and
      performance status (p = 0.027) increased for the entire group compared to
      preoperative values. CONCLUSION: Our data indicate that valve sparing aortic root
      reimplantation is safe and effective in septuagenarians, and is associated with
      low early and late morbidity and mortality.

PMID- 19383155
TI  - Comparative metagenomics of Daphnia symbionts.
AB  - BACKGROUND: Shotgun sequences of DNA extracts from whole organisms allow a
      comprehensive assessment of possible symbionts. The current project makes use of
      four shotgun datasets from three species of the planktonic freshwater crustaceans
      Daphnia: one dataset from clones of D. pulex and D. pulicaria and two datasets
      from one clone of D. magna. We analyzed these datasets with three aims: First, we
      search for bacterial symbionts, which are present in all three species. Second,
      we search for evidence for Cyanobacteria and plastids, which had been suggested
      to occur as symbionts in a related Daphnia species. Third, we compare the
      metacommunities revealed by two different 454 pyrosequencing methods (GS 20 and
      GS FLX). RESULTS: In all datasets we found evidence for a large number of
      bacteria belonging to diverse taxa. The vast majority of these were
      Proteobacteria. Of those, most sequences were assigned to different genera of the
      Betaproteobacteria family Comamonadaceae. Other taxa represented in all datasets
      included the genera Flavobacterium, Rhodobacter, Chromobacterium, Methylibium,
      Bordetella, Burkholderia and Cupriavidus. A few taxa matched sequences only from
      the D. pulex and the D. pulicaria datasets: Aeromonas, Pseudomonas and Delftia.
      Taxa with many hits specific to a single dataset were rare. For most of the
      identified taxa earlier studies reported the finding of related taxa in aquatic
      environmental samples. We found no clear evidence for the presence of symbiotic
      Cyanobacteria or plastids. The apparent similarity of the symbiont communities of
      the three Daphnia species breaks down on a species and strain level. Communities
      have a similar composition at a higher taxonomic level, but the actual sequences
      found are divergent. The two Daphnia magna datasets obtained from two different
      pyrosequencing platforms revealed rather similar results. CONCLUSION: Three
      clones from three species of the genus Daphnia were found to harbor a rich
      community of symbionts. These communities are similar at the genus and higher
      taxonomic level, but are composed of different species. The similarity of these
      three symbiont communities hints that some of these associations may be stable in
      the long-term.

PMID- 19383156
TI  - Reconstructing the phylogeny of 21 completely sequenced arthropod species based
      on their motor proteins.
AB  - BACKGROUND: Motor proteins have extensively been studied in the past and consist
      of large superfamilies. They are involved in diverse processes like cell
      division, cellular transport, neuronal transport processes, or muscle
      contraction, to name a few. Vertebrates contain up to 60 myosins and about the
      same number of kinesins that are spread over more than a dozen distinct classes.
      RESULTS: Here, we present the comparative genomic analysis of the motor protein
      repertoire of 21 completely sequenced arthropod species using the owl limpet
      Lottia gigantea as outgroup. Arthropods contain up to 17 myosins grouped into 13
      classes. The myosins are in almost all cases clear paralogs, and thus the
      evolution of the arthropod myosin inventory is mainly determined by gene losses.
      Arthropod species contain up to 29 kinesins spread over 13 classes. In contrast
      to the myosins, the evolution of the arthropod kinesin inventory is not only
      determined by gene losses but also by many subtaxon-specific and species-specific
      gene duplications. All arthropods contain each of the subunits of the cytoplasmic
      dynein/dynactin complex. Except for the dynein light chains and the p150 dynactin
      subunit they contain single gene copies of the other subunits. Especially the
      roadblock light chain repertoire is very species-specific. CONCLUSION: All 21
      completely sequenced arthropods, including the twelve sequenced Drosophila
      species, contain a species-specific set of motor proteins. The phylogenetic
      analysis of all genes as well as the protein repertoire placed Daphnia pulex
      closest to the root of the Arthropoda. The louse Pediculus humanus corporis is
      the closest relative to Daphnia followed by the group of the honeybee Apis
      mellifera and the jewel wasp Nasonia vitripennis. After this group the rust-red
      flour beetle Tribolium castaneum and the silkworm Bombyx mori diverged very
      closely from the lineage leading to the Drosophila species.

PMID- 19383158
TI  - The chemoreceptor genes of the waterflea Daphnia pulex: many Grs but no Ors.
AB  - BACKGROUND: Chemoreception is vitally important for all animals, yet little is
      known about the genetics of chemoreception in aquatic organisms. The keystone
      species Daphnia pulex, a well known crustacean, is the first aquatic invertebrate
      to have its genome sequenced. This has allowed us the initial investigation of
      chemoreceptor genes in an aquatic invertebrate, and to begin the study of
      chemoreceptor evolution across the arthropod phylum. RESULTS: We describe 58 Grs
      (gustatory receptors), belonging to the insect chemoreceptor superfamily, which
      were identified bioinformatically in the draft genome of the crustacean waterflea
      Daphnia pulex. No genes encoding proteins similar to the insect odorant receptors
      (Ors) were identified. These 58 Grs form 3 distinctive subfamilies of 37, 12, and
      5 genes, as well as a highly divergent singleton (Gr58). In addition, Grs55-57
      share distinctive amino acid motifs and cluster with the sugar receptors of
      insects, and may illuminate the origin of this distinctive subfamily. ESTs,
      tiling array, and PCR amplification results support 34 predicted gene models, and
      preliminary expression data comparing the sexes indicates potential female-biased
      expression for some genes. CONCLUSION: This repertoire of 58 chemoreceptors
      presumably mediates the many chemoperception abilities of waterfleas. While it is
      always possible that the entire Or gene lineage was lost at some point in the
      history of Daphnia pulex, we think it more likely that the insect Or lineage is
      indeed a relatively recently expanded gene lineage concomitant with the evolution
      of terrestriality in the insects or their hexapod ancestors.

PMID- 19383157
TI  - Meiosis genes in Daphnia pulex and the role of parthenogenesis in genome
      evolution.
AB  - BACKGROUND: Thousands of parthenogenetic animal species have been described and
      cytogenetic manifestations of this reproductive mode are well known. However,
      little is understood about the molecular determinants of parthenogenesis. The
      Daphnia pulex genome must contain the molecular machinery for different
      reproductive modes: sexual (both male and female meiosis) and parthenogenetic
      (which is either cyclical or obligate). This feature makes D. pulex an ideal
      model to investigate the genetic basis of parthenogenesis and its consequences
      for gene and genome evolution. Here we describe the inventory of meiotic genes
      and their expression patterns during meiotic and parthenogenetic reproduction to
      help address whether parthenogenesis uses existing meiotic and mitotic machinery,
      or whether novel processes may be involved. RESULTS: We report an inventory of
      130 homologs representing over 40 genes encoding proteins with diverse roles in
      meiotic processes in the genome of D. pulex. Many genes involved in cell cycle
      regulation and sister chromatid cohesion are characterized by expansions in copy
      number. In contrast, most genes involved in DNA replication and homologous
      recombination are present as single copies. Notably, RECQ2 (which suppresses
      homologous recombination) is present in multiple copies while DMC1 is the only
      gene in our inventory that is absent in the Daphnia genome. Expression patterns
      for 44 gene copies were similar during meiosis versus parthenogenesis, although
      several genes displayed marked differences in expression level in germline and
      somatic tissues. CONCLUSION: We propose that expansions in meiotic gene families
      in D. pulex may be associated with parthenogenesis. Taking into account our
      findings, we provide a mechanistic model of parthenogenesis, highlighting steps
      that must differ from meiosis including sister chromatid cohesion and kinetochore
      attachment.

PMID- 19383159
TI  - ESTPiper--a web-based analysis pipeline for expressed sequence tags.
AB  - BACKGROUND: EST sequencing projects are increasing in scale and scope as the
      genome sequencing technologies migrate from core sequencing centers to individual
      research laboratories. Effectively, generating EST data is no longer a bottleneck
      for investigators. However, processing large amounts of EST data remains a non
      trivial challenge for many. Web-based EST analysis tools are proving to be the
      most convenient option for biologists when performing their analysis, so these
      tools must continuously improve on their utility to keep in step with the growing
      needs of research communities. We have developed a web-based EST analysis
      pipeline called ESTPiper, which streamlines typical large-scale EST analysis
      components. RESULTS: The intuitive web interface guides users through each step
      of base calling, data cleaning, assembly, genome alignment, annotation, analysis
      of gene ontology (GO), and microarray oligonucleotide probe design. Each step is
      modularized. Therefore, a user can execute them separately or together in batch
      mode. In addition, the user has control over the parameters used by the
      underlying programs. Extensive documentation of ESTPiper's functionality is
      embedded throughout the web site to facilitate understanding of the required
      input and interpretation of the computational results. The user can also download
      intermediate results and port files to separate programs for further analysis. In
      addition, our server provides a time-stamped description of the run history for
      reproducibility. The pipeline can also be installed locally, allowing researchers
      to modify ESTPiper to suit their own needs. CONCLUSION: ESTPiper streamlines the
      typical process of EST analysis. The pipeline was initially designed in part to
      support the Daphnia pulex cDNA sequencing project. A web server hosting ESTPiper
      is provided at http://estpiper.cgb.indiana.edu/ to now support projects of all
      size. The software is also freely available from the authors for local
      installations.

PMID- 19383161
TI  - Direct intra-abdominal pressure monitoring via piezoresistive pressure
      measurement: a technical note.
AB  - BACKGROUND: Piezoresistive pressure measurement technique (PRM) has previously
      been applied for direct IAP measurement in a porcine model using two different
      devices. Aim of this clinical study was to assess both devices regarding
      complications, reliability and agreement with IVP in patients undergoing elective
      abdominal surgery. METHODS: A prospective cohort study was performed in 20
      patients randomly scheduled to receive PRM either by a Coach-probe or an
      Accurate(++)-probe (both MIPM, Mammendorf, Germany). Probes were placed on the
      greater omentum and passed through the abdominal wall paralleling routine
      drainages. PRM was compared with IVP measurement by t-testing and by calculating
      mean difference as well as limits of agreement (LA). RESULTS: There were no probe
      related complications. Due to technical limitations, data could be collected in
      3/10 patients with Coach and in 7/10 patients with Accurate++. Analysis was
      carried out only for Accurate++. Mean values did not differ to mean IVP values.
      Mean difference to IVP was 0.1 +/- 2.8 mmHg (LA: -5.5 to 5.6 mmHg). CONCLUSION:
      Direct IAP measurement was clinically uneventful. Although results of Accurate++
      were comparable to IVP, the device might be too fragile for IAP measurements in
      the clinical setting. Local ethical committee trial registration: EK2024.

PMID- 19383160
TI  - Effects of low-dye taping on plantar pressure pre and post exercise: an
      exploratory study.
AB  - BACKGROUND: Low-Dye taping is used for excessive pronation at the subtalar joint
      of the foot. Previous research has focused on the tape's immediate effect on
      plantar pressure. Its effectiveness following exercise has not been investigated.
      Peak plantar pressure distribution provides an indirect representation of
      subtalar joint kinematics. The objectives of the study were 1) To determine the
      effects of Low-Dye taping on peak plantar pressure immediately post-application.
      2) To determine whether any initial effects are maintained following exercise.
      METHODS: 12 asymptomatic subjects participated; each being screened for excessive
      pronation (navicular drop > 10 mm). Plantar pressure data was recorded, using the
      F-scan, at four intervals during the testing session: un-taped, baseline-taped,
      post-exercise session 1, and post-exercise session 2. Each exercise session
      consisted of a 10-minute walk at a normal pace. The foot was divided into 6
      regions during data analysis. Repeated-measures analysis of variance (ANOVA) was
      used to assess regional pressure variations across the four testing conditions.
      RESULTS: Reduced lateral forefoot peak plantar pressure was the only significant
      difference immediately post tape application (p = 0.039). This effect was lost
      after 10 minutes of exercise (p = 0.036). Each exercise session resulted in
      significantly higher medial forefoot peak pressure compared to un-taped; (p =
      0.015) and (p = 0.014) respectively, and baseline-taped; (p = 0.036) and (p =
      0.015) respectively. Medial and lateral rearfoot values had also increased after
      the second session (p = 0.004), following their non-significant reduction at
      baseline-taped. A trend towards a medial-to-lateral shift in pressure present in
      the midfoot immediately following tape application was still present after 20
      minutes of exercise. CONCLUSION: Low-Dye tape's initial effect of reduced lateral
      forefoot peak plantar pressure was lost after a 10-minute walk. However, the tape
      continued to have an effect on the medial forefoot after 20 minutes of exercise.
      Further studies with larger sample sizes are required to examine the important
      finding of the anti-pronatory trend present in the midfoot.

PMID- 19383162
TI  - Development of functional gastrointestinal disorders after Giardia lamblia
      infection.
AB  - BACKGROUND: Functional gastrointestinal disorders (FGID) may occur following
      acute gastroenteritis. This long-term complication has previously not been
      described after infection with the non-invasive protozoan Giardia lamblia. This
      study aims to characterize persistent abdominal symptoms elicited by Giardia
      infection according to Rome II criteria and symptoms scores. METHODS: Structured
      interview and questionnaires 12-30 months after the onset of Giardia infection,
      and at least 6 months after Giardia eradication, among 82 patients with
      persisting abdominal symptoms elicited by the Giardia infection. All had been
      evaluated to exclude other causes. RESULTS: We found that 66 (80.5%) of the 82
      patients had symptoms consistent with irritable bowel syndrome (IBS) and 17
      (24.3%) patients had functional dyspepsia (FD) according to Rome II criteria. IBS
      was sub classified into D-IBS (47.0%), A-IBS (45.5%) and C-IBS (7.6%). Bloating,
      diarrhoea and abdominal pain were reported to be most severe. Symptoms
      exacerbation related to specific foods were reported by 45 (57.7%) patients and
      to physical or mental stress by 34 (44.7%) patients. CONCLUSION: In the presence
      of an IBS-subtype pattern consistent with post-infectious IBS (PI-IBS), and in
      the absence of any other plausible causes, we conclude that acute Giardia
      infection may elicit functional gastrointestinal diseases with food and stress
      related symptoms similar to FGID patients in general.

PMID- 19383163
TI  - Ecological and genetic relationships of the Forest-M form among chromosomal and
      molecular forms of the malaria vector Anopheles gambiae sensu stricto.
AB  - BACKGROUND: Anopheles gambiae sensu stricto, one of the principal vectors of
      malaria, has been divided into two subspecific groups, known as the M and S
      molecular forms. Recent studies suggest that the M form found in Cameroon is
      genetically distinct from the M form found in Mali and elsewhere in West Africa,
      suggesting further subdivision within that form. METHODS: Chromosomal,
      microsatellite and geographic/ecological evidence are synthesized to identify
      sources of genetic polymorphism among chromosomal and molecular forms of the
      malaria vector Anopheles gambiae s.s. RESULTS: Cytogenetically the Forest M form
      is characterized as carrying the standard chromosome arrangement for six major
      chromosomal inversions, namely 2La, 2Rj, 2Rb, 2Rc, 2Rd, and 2Ru. Bayesian
      clustering analysis based on molecular form and chromosome inversion
      polymorphisms as well as microsatellites describe the Forest M form as a distinct
      population relative to the West African M form (Mopti-M form) and the S form. The
      Forest-M form was the most highly diverged of the An. gambiae s.s. groups based
      on microsatellite markers. The prevalence of the Forest M form was highly
      correlated with precipitation, suggesting that this form prefers much wetter
      environments than the Mopti-M form. CONCLUSION: Chromosome inversions,
      microsatellite allele frequencies and habitat preference all indicate that the
      Forest M form of An. gambiae is genetically distinct from the other recognized
      forms within the taxon Anopheles gambiae sensu stricto. Since this study covers
      limited regions of Cameroon, the possibility of gene flow between the Forest-M
      form and Mopti-M form cannot be rejected. However, association studies of
      important phenotypes, such as insecticide resistance and refractoriness against
      malaria parasites, should take into consideration this complex population
      structure.

PMID- 19383164
TI  - Remifentanil discontinuation and subsequent intensive care unit-acquired
      infection: a cohort study.
AB  - INTRODUCTION: Recent animal studies demonstrated immunosuppressive effects of
      opioid withdrawal resulting in a higher risk of infection. The aim of this study
      was to determine the impact of remifentanil discontinuation on intensive care
      unit (ICU)-acquired infection. METHODS: This was a prospective observational
      cohort study performed in a 30-bed medical and surgical university ICU, during a
      one-year period. All patients hospitalised in the ICU for more than 48 hours were
      eligible. Sedation was based on a written protocol including remifentanil with or
      without midazolam. Ramsay score was used to evaluate consciousness. The bedside
      nurse adjusted sedative infusion to obtain the target Ramsay score. Univariate
      and multivariate analyses were performed to determine risk factors for ICU
      acquired infection. RESULTS: Five hundred and eighty-seven consecutive patients
      were included in the study. A microbiologically confirmed ICU-acquired infection
      was diagnosed in 233 (39%) patients. Incidence rate of ICU-acquired infection was
      38 per 1000 ICU-days. Ventilator-associated pneumonia was the most frequently
      diagnosed ICU-acquired infection (23% of study patients). Pseudomonas aeruginosa
      was the most frequently isolated microorganism (30%). Multivariate analysis
      identified remifentanil discontinuation (odds ratio (OR) = 2.53, 95% confidence
      interval (CI) = 1.28 to 4.99, P = 0.007), simplified acute physiology score II at
      ICU admission (1.01 per point, 95% CI = 1 to 1.03, P = 0.011), mechanical
      ventilation (4.49, 95% CI = 1.52 to 13.2, P = 0.006), tracheostomy (2.25, 95% CI
      = 1.13 to 4.48, P = 0.021), central venous catheter (2.9, 95% CI = 1.08 to 7.74,
      P = 0.033) and length of hospital stay (1.05 per day, 95% CI = 1.03 to 1.08, P <
      0.001) as independent risk factors for ICU-acquired infection. CONCLUSIONS:
      Remifentanil discontinuation is independently associated with ICU-acquired
      infection.

PMID- 19383165
TI  - New insights into the functions and regulation of the transcriptional
      corepressors SMRT and N-CoR.
AB  - Corepressors are large proteins that facilitate transcriptional repression
      through recruitment of histone-modifying enzymes. Two major corepressors, SMRT
      (silencing mediator for retinoid and thyroid hormone receptors) and N-CoR
      (nuclear receptor corepressor), have been shown to mediate repression associated
      with nuclear receptors and a myriad of other transcription factors. This review
      will focus on recent studies on these proteins, including newly discovered
      physiological roles of the corepressors, their modes of regulation, their roles
      in antiestrogen-resistant breast cancer and their functions during the cell
      cycle.

PMID- 19383166
TI  - On the edge of Bantu expansions: mtDNA, Y chromosome and lactase persistence
      genetic variation in southwestern Angola.
AB  - BACKGROUND: Current information about the expansion of Bantu-speaking peoples is
      hampered by the scarcity of genetic data from well identified populations from
      southern Africa. Here, we fill an important gap in the analysis of the western
      edge of the Bantu migrations by studying for the first time the patterns of Y
      chromosome, mtDNA and lactase persistence genetic variation in four
      representative groups living around the Namib Desert in southwestern Angola
      (Ovimbundu, Ganguela, Nyaneka-Nkumbi and Kuvale). We assessed the differentiation
      between these populations and their levels of admixture with Khoe-San groups, and
      examined their relationship with other sub-Saharan populations. We further
      combined our dataset with previously published data on Y-chromosome and mtDNA
      variation to explore a general isolation with migration model and infer the
      demographic parameters underlying current genetic diversity in Bantu populations.
      RESULTS: Correspondence analysis, lineage sharing patterns and admixture
      estimates indicate that the gene pool from southwestern Angola is predominantly
      derived from West-Central Africa. The pastoralist Herero-speaking Kuvale people
      were additionally characterized by relatively high frequencies of Y-chromosome
      (12%) and mtDNA (22%) Khoe-San lineages, as well as by the presence of the 
      14010C lactase persistence mutation (6%), which likely originated in non-Bantu
      pastoralists from East Africa. Inferred demographic parameters show that both
      male and female populations underwent significant size growth after the split
      between the western and eastern branches of Bantu expansions occurring 4000 years
      ago. However, males had lower population sizes and migration rates than females
      throughout the Bantu dispersals. CONCLUSION: Genetic variation in southwestern
      Angola essentially results from the encounter of an offshoot of West-Central
      Africa with autochthonous Khoisan-speaking peoples from the south. Interactions
      between the Bantus and the Khoe-San likely involved cattle herders from the two
      groups sharing common aspects of their social organization. The presence of the 
      14010C mutation in southwestern Angola provides a link between the East and
      Southwest African pastoral scenes that might have been established indirectly,
      through migrations of Khoe herders across southern Africa. Differences in
      patterns of mtDNA and Y-chromosome intrapopulation diversity and interpopulation
      differentiation may be explained by contrasting demographic histories underlying
      the current female and male genetic variation.

PMID- 19383167
TI  - Positive selection and ancient duplications in the evolution of class B floral
      homeotic genes of orchids and grasses.
AB  - BACKGROUND: Positive selection is recognized as the prevalence of nonsynonymous
      over synonymous substitutions in a gene. Models of the functional evolution of
      duplicated genes consider neofunctionalization as key to the retention of
      paralogues. For instance, duplicate transcription factors are specifically
      retained in plant and animal genomes and both positive selection and
      transcriptional divergence appear to have played a role in their diversification.
      However, the relative impact of these two factors has not been systematically
      evaluated. Class B MADS-box genes, comprising DEF-like and GLO-like genes, encode
      developmental transcription factors essential for establishment of perianth and
      male organ identity in the flowers of angiosperms. Here, we contrast the role of
      positive selection and the known divergence in expression patterns of genes
      encoding class B-like MADS-box transcription factors from monocots, with emphasis
      on the family Orchidaceae and the order Poales. Although in the monocots these
      two groups are highly diverse and have a strongly canalized floral morphology,
      there is no information on the role of positive selection in the evolution of
      their distinctive flower morphologies. Published research shows that in Poales,
      class B-like genes are expressed in stamens and in lodicules, the perianth organs
      whose identity might also be specified by class B-like genes, like the identity
      of the inner tepals of their lily-like relatives. In orchids, however, the number
      and pattern of expression of class B-like genes have greatly diverged. RESULTS:
      The DEF-like genes from Orchidaceae form four well-supported, ancient clades of
      orthologues. In contrast, orchid GLO-like genes form a single clade of ancient
      orthologues and recent paralogues. DEF-like genes from orchid clade 2 (OMADS3
      like genes) are under less stringent purifying selection than the other orchid
      DEF-like and GLO-like genes. In comparison with orchids, purifying selection was
      less stringent in DEF-like and GLO-like genes from Poales. Most importantly,
      positive selection took place before the major organ reduction and losses in the
      floral axis that eventually yielded the zygomorphic grass floret. CONCLUSION: In
      DEF-like genes of Poales, positive selection on the region mediating interactions
      with other proteins or DNA could have triggered the evolution of the regulatory
      mechanisms behind the development of grass-specific reproductive structures.
      Orchidaceae show a different trend, where gene duplication and transcriptional
      divergence appear to have played a major role in the canalization and
      modularization of perianth development.

PMID- 19383168
TI  - Design of a study on suboptimal cognitive acts in the diagnostic process, the
      effect on patient outcomes and the influence of workload, fatigue and experience
      of physician.
AB  - BACKGROUND: Diagnostic error is an important error type since diagnostic adverse
      events are regularly judged as being preventable and the consequences are
      considered to be severe. Existing research often focuses on either diagnostic
      adverse events or on the errors in diagnostic reasoning. Whether and when an
      incorrect diagnostic process results in adverse outcomes has not been studied
      extensively. The present paper describes the design of a study that aims to study
      the relationship between a suboptimal diagnostic process and patient outcomes. In
      addition, the role of personal and circumstantial factors on the quality of the
      diagnostic process will be examined. METHODS/DESIGN: The research questions were
      addressed using several data sources. First, the differential diagnosis was
      assessed concurrently to the diagnostic process. Second, the patient records of
      248 patients suffering from shortness of breath were reviewed by expert
      internists in order to reveal suboptimal cognitive acts and (potential)
      consequences for the patient. The suboptimal cognitive acts were discussed with
      the treating physicians and classified with the taxonomy of unsafe acts. Third,
      workload, fatigue and work experience were measured during the physicians work.
      Workload and fatigue were measured during the physicians shift using the NASA tlx
      questionnaire on a handheld computer. Physicians participating in the study also
      answered questions about their work experience. DISCUSSION: The design used in
      this study provides insight into the relationship between suboptimal cognitive
      acts in the diagnostic process and possible consequences for the patient.
      Suboptimal cognitive acts in the diagnostic process and its causes can be
      revealed. Additional measurements of workload, fatigue and experience allow
      examining the influence of these factors on the diagnostic process. In
      conclusion, the present design provides a method with which insights in
      weaknesses of the diagnostic process and the effect on patient outcomes can be
      studied and opportunities for improvement can be obtained.

PMID- 19383170
TI  - Serum markers in interstitial pneumonia with and without Pneumocystis jirovecii
      colonization: a prospective study.
AB  - BACKGROUND: In patients with chronic respiratory disease, Pneumocystis jirovecii
      (P. jirovecii) colonization is observed, and may influence disease progression
      and systemic inflammation. Pneumocystis pneumonia causes interstitial changes, so
      making a diagnosis of PCP in patients who have interstitial pneumonia (IP) with
      P. jirovecii colonization is sometimes difficult based on radiography. METHODS:
      This study investigated the prevalence of P. jirovecii colonization in IP
      patients and assessed pulmonary injury due to P. jirovecii colonization by
      measurement of serum markers (KL-6, SP-A, SP-D, and (1-->3) beta-D-glucan (beta-D
      glucan)) and the peripheral lymphocyte counts, prospectively. A total of 75
      patients with idiopathic pulmonary fibrosis (n = 29), collagen vascular-related
      interstitial pneumonia (n = 19), chronic bronchitis or pneumonia (n = 20), and
      Pneumocystis pneumonia (n = 7) were enrolled in this prospective study. P.
      jirovecii DNA was detected in sputum samples, while serum markers and the
      lymphocyte count were measured in the peripheral blood. RESULTS: IP patients
      (idiopathic pulmonary fibrosis and collagen vascular-related IP) who received
      oral corticosteroids had a high prevalence of P. jirovecii colonization (23.3%).
      In IP patients, oral corticosteroid therapy was a significant risk factor for P.
      jirovecii colonization (P < 0.05). Serum markers did not show differences between
      IP patients with and without P. jirovecii colonization. The beta-D-glucan level
      and lymphocyte count differed between patients with Pneumocystis pneumonia or P.
      jirovecii colonization. CONCLUSION: Serum levels of KL-6, SP-A, SP-D, and beta-D
      glucan were not useful for detecting P. jirovecii colonization in IP patients.
      However, the serum beta-D-glucan level and lymphocyte count were useful for
      distinguishing P. jirovecii colonization from pneumocystis pneumonia in IP
      patients.

PMID- 19383169
TI  - Prevalence of metabolic syndrome in scholars from Bucaramanga, Colombia: a
      population-based study.
AB  - BACKGROUND: Obesity and metabolic syndrome are strongly associated with type 2
      diabetes mellitus and cardiovascular diseases, thus the increasing trend in their
      prevalence among children and adolescents from developing countries requires a
      further understanding of their epidemiology and determinants. METHODS AND DESIGN:
      A cross-sectional study was designed to determine the prevalence of metabolic
      syndrome among 6-10 year-old children from Bucaramanga, Colombia. A two-stage
      random-cluster (neighborhoods, houses) sampling process was performed based on
      local city maps and local statistics. The study involves a domiciliary survey;
      including a comprehensive socio-demographic, nutritional and physical activity
      characterization of the children that participated in the study, followed by a
      complete clinical examination; including blood pressure, anthropometry, lipid
      profile determination, fasting glucose and insulin levels. The prevalence of
      metabolic syndrome will be determined using definitions and specific percentile
      cut-off points for this population. Finally, the association between components
      of metabolic syndrome and higher degrees of insulin resistance will be analyzed
      through a multivariable logistic regression model. This study protocol was
      designed in compliance with the Helsinki declaration and approved by the local
      ethics board. Consent was obtained from the children and their parents/guardians.
      DISCUSSION: A complete description of the environmental and non-environmental
      factors underlying the burden of metabolic syndrome in children from a developing
      country like Colombia will provide policy makers, health care providers and
      educators from similar settings with an opportunity to guide primary and
      secondary preventive initiatives at both individual and community levels.
      Moreover, this description may give an insight into the pathophysiological
      mechanisms mediating the development of cardio-metabolic diseases early in life.

PMID- 19383171
TI  - Early initiation of sexual activity: a risk factor for sexually transmitted
      diseases, HIV infection, and unwanted pregnancy among university students in
      China.
AB  - BACKGROUND: To explore any association between the timing of the initiation of
      sexual activity and sexual behaviors and risks among university students in
      China. METHODS: Data were derived from a cross-sectional study on sexual behavior
      among university students conducted in Ningbo municipality, China, at the end of
      2003. Students completed a self-administered, structured questionnaire. Of 1981
      sexually active male students, 1908 (96.3%) completed the item for timing of the
      initiation of sexual activity and were included in bivariate trend analyses and
      multiple logistic regression analyses to compare the association between this
      timing and sexual behavior and risks. RESULTS: Male early sexual initiators had a
      significantly higher risk profile, including a significantly higher proportion
      reporting non-regular partners (i.e., casual or commercial partners), multiple
      partners, diagnosis with a sexually transmitted disease (STD), partner history of
      pregnancy, partner history of induced abortion, and less condom and oral
      contraceptive use, compared with late initiators. Multivariate analyses confirmed
      the increased likelihood of these risks in early initiators versus late
      initiators, other than partner type during the last year. CONCLUSION: Our results
      showed that, compared to late initiators, people who initiated sexual activity
      early engaged in more risky behaviors that could lead to elevated risks of
      unwanted pregnancies and STDs or human immunodeficiency virus infection. Sex
      education strategies should be focused on an earlier age, should include advice
      on delaying the age of first sexual activity, and should target young people who
      continue to take sexual risks.

PMID- 19383172
TI  - Revisiting perioperative chemotherapy: the critical importance of targeting
      residual cancer prior to wound healing.
AB  - BACKGROUND: Scientists and physicians have long noted similarities between the
      general behavior of a cancerous tumor and the physiological process of wound
      healing. But it may be during metastasis that the parallels between cancer and
      wound healing are most pronounced. And more particularly and for the reasons
      detailed in this paper, any cancer remaining after the removal of a solid tumor,
      whether found in micrometastatic deposits in the stroma or within the
      circulation, may be heavily dependent on wound healing pathways for its further
      survival and proliferation. DISCUSSION: If cancer cells can hijack the wound
      healing process to facilitate their metastatic spread and survival, then the
      period immediately after surgery may be a particularly vulnerable period of time
      for the host, as wound healing pathways are activated and amplified after the
      primary tumor is removed. Given that we often wait 30 days or more after surgical
      removal of the primary tumor before initiating adjuvant chemotherapy to allow
      time for the wound to heal, this paper challenges the wisdom of that clinical
      paradigm, providing a theoretical rationale for administering therapy during the
      perioperative period. SUMMARY: Waiting for wound healing to occur before
      initiating adjuvant therapies may be seriously compromising their effectiveness,
      and patients subsequently rendered incurable as a result of this wait. Clinical
      trials to establish the safety and effectiveness of administering adjuvant
      therapies perioperatively are needed. These therapies should target not only the
      residual cancer cells, but also the wound healing pathway utilized by these cells
      to proliferate and metastasize.

PMID- 19383173
TI  - High retention and appropriate use of insecticide-treated nets distributed to HIV
      affected households in Rakai, Uganda: results from interviews and home visits.
AB  - BACKGROUND: Distribution of insecticide-treated nets (ITNs) has recently been
      incorporated into comprehensive care strategies for HIV-positive people in
      malaria-endemic areas. WHO now recommends free or low-cost distribution of ITNs
      to all persons in malaria-endemic areas, regardless of age, pregnancy and HIV
      status. Knowledge about and appropriate use of ITNs among HIV-positive ITN
      recipients and their household members has not been well characterized. METHODS:
      142 randomly selected adults were interviewed in July-August 2006 to assess
      knowledge, retention, and appropriate use of ITNs they had received through a
      PEPFAR-funded comprehensive HIV care programme in rural Uganda. RESULTS: Among
      all participants, 102 (72%, CI: 65%-79%) reported they had no ITNs except those
      provided by the programme. Of 131 participants who stated they were given >or= 1
      ITN, 128 (98%, CI: 96%-100%) stated they still possessed at least one programme
      provided ITN. Reported programme-ITN (pITN) use by participants was high: 119
      participants (91%, CI: 86%-96%) reported having slept under pITN the night prior
      to the survey and 115 (88%, CI: 82%-94%) reported sleeping under pITN seven days
      per week. Being away from home and heat were the most common reasons given for
      not sleeping under an ITN. A sub-study of thirteen random home visits
      demonstrated concordance between participants' survey reports and actual use of
      ITNs in homes. CONCLUSION: There was excellent self-reported retention and
      appropriate use of ITNs distributed as a part of a community-based outpatient HIV
      care programme. Participants perceived ITNs as useful and were unlikely to have
      received ITNs from other sources.

PMID- 19383174
TI  - Hexa-arginine enhanced uptake and residualization of selective high affinity
      ligands by Raji lymphoma cells.
AB  - BACKGROUND: A variety of arginine-rich peptide sequences similar to those found
      in viral proteins have been conjugated to other molecules to facilitate their
      transport into the cytoplasm and nucleus of targeted cells. The selective high
      affinity ligand (SHAL) (DvLPBaPPP)2LLDo, which was developed to bind only to
      cells expressing HLA-DR10, has been conjugated to one of these peptide
      transduction domains, hexa-arginine, to assess the impact of the peptide on SHAL
      uptake and internalization by Raji cells, a B-cell lymphoma. RESULTS: An analog
      of the SHAL (DvLPBaPPP)2LLDo containing a hexa-arginine peptide was created by
      adding six D-arginine residues sequentially to a lysine inserted in the SHAL's
      linker. SHAL binding, internalization and residualization by Raji cells
      expressing HLA-DR10 were examined using whole cell binding assays and confocal
      microscopy. Raji cells were observed to bind two fold more 111In-labeled hexa
      arginine SHAL analog than Raji cells treated with the parent SHAL. Three fold
      more hexa-arginine SHAL remained associated with the Raji cells after washing,
      suggesting that the peptide also enhanced residualization of the 111In
      transported into cells. Confocal microscopy showed both SHALs localized in the
      cytoplasm of Raji cells, whereas a fraction of the hexa-arginine SHAL localized
      in the nucleus. CONCLUSION: The incorporation of a hexa-D-arginine peptide into
      the linker of the SHAL (DvLPBaPPP)2LLDo enhanced both the uptake and
      residualization of the SHAL analog by Raji cells. In contrast to the abundant
      cell surface binding observed with Lym-1 antibody, the majority of
      (DvLPBaPPP)2LArg6AcLLDo and the parent SHAL were internalized. Some of the
      internalized hexa-arginine SHAL analog was also associated with the nucleus.
      These results demonstrate that several important SHAL properties, including
      uptake, internalization, retention and possibly intracellular distribution, can
      be enhanced or modified by conjugating the SHALs to a short polypeptide.

PMID- 19383175
TI  - Ecto-nucleoside triphosphate diphosphohydrolase 3 in the ventral and lateral
      hypothalamic area of female rats: morphological characterization and functional
      implications.
AB  - BACKGROUND: Based on its distribution in the brain, ecto-nucleoside triphosphate
      diphosphohydrolase 3 (NTPDase3) may play a role in the hypothalamic regulation of
      homeostatic systems, including feeding, sleep-wake behavior and reproduction. To
      further characterize the morphological attributes of NTPDase3-immunoreactive (IR)
      hypothalamic structures in the rat brain, here we investigated: 1.) The cellular
      and subcellular localization of NTPDase3; 2.) The effects of 17beta-estradiol on
      the expression level of hypothalamic NTPDase3; and 3.) The effects of NTPDase
      inhibition in hypothalamic synaptosomal preparations. METHODS: Combined light-
      and electron microscopic analyses were carried out to characterize the cellular
      and subcellular localization of NTPDase3-immunoreactivity. The effects of
      estrogen on hypothalamic NTPDase3 expression was studied by western blot
      technique. Finally, the effects of NTPDase inhibition on mitochondrial
      respiration were investigated using a Clark-type oxygen electrode. RESULTS:
      Combined light- and electron microscopic analysis of immunostained hypothalamic
      slices revealed that NTPDase3-IR is linked to ribosomes and mitochondria, is
      predominantly present in excitatory axon terminals and in distinct segments of
      the perikaryal plasma membrane. Immunohistochemical labeling of NTPDase3 and
      glutamic acid decarboxylase (GAD) indicated that gamma-amino-butyric-acid- (GABA)
      ergic hypothalamic neurons do not express NTPDase3, further suggesting that in
      the hypothalamus, NTPDase3 is predominantly present in excitatory neurons. We
      also investigated whether estrogen influences the expression level of NTPDase3 in
      the ventrobasal and lateral hypothalamus. A single subcutaneous injection of
      estrogen differentially increased NTPDase3 expression in the medial and lateral
      parts of the hypothalamus, indicating that this enzyme likely plays region
      specific roles in estrogen-dependent hypothalamic regulatory mechanisms.
      Determination of mitochondrial respiration rates with and without the inhibition
      of NTPDases confirmed the presence of NTPDases, including NTPDase3 in neuronal
      mitochondria and showed that blockade of mitochondrial NTPDase functions
      decreases state 3 mitochondrial respiration rate and total mitochondrial
      respiratory capacity. CONCLUSION: Altogether, these results suggest the
      possibility that NTPDases, among them NTPDase3, may play an estrogen-dependent
      modulatory role in the regulation of intracellular availability of ATP needed for
      excitatory neuronal functions including neurotransmission.

PMID- 19383176
TI  - Development of Danish version of child oral-health-related quality of life
      questionnaires (CPQ8-10 and CPQ11-14).
AB  - BACKGROUND: The Child Perceptions Questionnaire (CPQ) is a self-reported
      questionnaire developed to measure oral health-related quality of life in
      children. The CPQ aims to improve the description of children's oral health,
      while taking into consideration the importance of psychological aspects in the
      concept of health. The CPQ exists in two versions: the CPQ8-10 for children aged
      8-10 years and the CPQ11-14 for those aged 11-14 years. The aim of this study was
      to develop a Danish version of the CPQ8-10 and the CPQ11-14 and to evaluate its
      validity for use among Danish-speaking children. METHODS: The instruments were
      translated from English into Danish in accordance with a recommended translation
      procedure. Afterwards, they were tested among children aged 8-10 (n = 120) and 11
      14 years (n = 225). The validity was expressed by the correlation between overall
      CPQ scores and i) self-reported assessment of the influence of oral conditions on
      everyday life (not at all, very little, some, a lot, very much) and ii) the self
      reported rating of oral health. Furthermore, groups of children with assumed
      decreased oral health-related quality of life were compared with children with
      healthy oral conditions. Finally, we examined the internal consistency. RESULTS:
      The correlation between overall CPQ scores and global assessments of the
      influence of oral conditions on everyday life showed Spearman correlation
      coefficients of 0.45, P < 0.001 for CPQ8-10 and 0.50, P < 0.001 for CPQ11-14. The
      correlation between overall CPQ scores and the self-reported rating of oral
      health showed Spearman correlation coefficients of 0.45, P < 0.001 for CPQ8-10
      and 0.17, P = 0.010 for CPQ11-14.The median overall CPQ8-10 scores were 7 for
      individuals with healthy oral conditions, 5 for individuals with cleft lip and
      palate, and 15 for individuals with rare oral diseases. The median overall CPQ11
      14 scores were 9 for individuals with healthy oral conditions, 9 for individuals
      with cleft lip and palate, 17.0 for individuals with rare oral diseases, and 22.0
      for individuals with fixed orthodontic appliances. There were statistically
      significant differences between the groups of children with healthy oral
      conditions and each of the subgroups, except for children with cleft lip and
      palate.Chronbach'alpha were 0.82 for CPQ8-10 and 0.87 for CPQ11-14. CONCLUSION:
      The results of this study reveal that the Danish CPQ8-10 and CPQ11-14, seem to be
      valid instruments for measuring oral health-related quality of life in children
      although its ability to discriminate between children with cleft lip and palate
      and healthy children seem to be limited.

PMID- 19383179
TI  - The impact of treatment of the fetus by maternal therapy on the fetal and
      postnatal outcomes for fetuses diagnosed with isolated complete atrioventricular
      block.
AB  - OBJECTIVES: to analyse retrospectively the data of fetuses diagnosed with
      isolated complete atrioventricular block and efficacy of treatment of the fetus
      by maternal therapy. MATERIALS: Between 1992 and 2004, we diagnosed complete
      atrioventricular block in 26 singleton and 2 twins fetuses of 27 pregnant women
      known to have anti Ro/La antibodies, 11 with autoimmune disease, one patient
      analysed in 2 pregnancies. At presentation, 20 of the fetuses were compensated
      and non-hydropic, while 8 had hydrops. Twenty patients were treated with
      dexamethasone, 2 with associated salbutamol and one mother with isoproterenol.
      RESULTS: Age at presentation was not different between the hydropic and non
      hydropic fetuses. The fetuses with hydrops, however, had a lower mean heart rate
      at presentation, 48.5 +/- 9.25 with a range from 32 to 60, compared to 59.95 +/-
      7.9 beats per minute, with a range from 50 to 80, in the non-hydropic fetuses (p
      less than 0.002). Equally, after birth the mean heart rate in hydropic fetuses
      was 42.6 +/- 5.1, with a range from 38 to 50, as opposed to 56.05 +/- 11.8 beats
      per minute, with a range from 29 to 110, in the non-hydropic fetuses (p less than
      0.015), The hydropic fetuses were delivered at 31.7 +/- 3.8 weeks' gestation,
      with a range from 29 to 38 weeks (p less than 0.003) compared to 35.5 weeks'
      gestation +/-2.04, with a range from 31 to 38, in the non-hydropic fetuses.
      Mortality was 37.5% in the hydropic fetuses, versus 5% of those without hydrops
      (p less than 0.02). Pacemakers were implanted in 22 of 26 infants born alive, at
      a median of 45 days, with a range from 1 day to 5 years, in those without hydrops
      during fetal life, and 3 days, with a range from 1 day to 8 months in those
      afflicted by hydrops, of whom 2 died despite the implant of the pacemaker. The
      presence and degree of hydrops had a significantly negative predictive value. No
      significant differences were observed between the treated and non treated cases,
      albeit that administration of steroids ameliorated rapidly the hydrops in 3 of 5
      cases. CONCLUSIONS: The outcome in our cases was mainly dependent on the presence
      and degree of fetal cardiac failure. Treatment of the fetus by maternal
      administration of steroids did not result in any regression of the conduction
      disorder, but had a favourable effect on fetal hydrops.

PMID- 19383177
TI  - Horse bone marrow mesenchymal stem cells express embryo stem cell markers and
      show the ability for tenogenic differentiation by in vitro exposure to BMP-12.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have been recently investigated for
      their potential use in regenerative medicine. MSCs, in particular, have great
      potential, as in various reports they have shown pluripotency for differentiating
      into many different cell types. However, the ability of MSCs to differentiate
      into tendon cells in vitro has not been fully investigated. RESULTS: In this
      study, we show that equine bone marrow mesenchymal stem cells (BM-MSCs), defined
      by their expression of markers such as Oct4, Sox-2 and Nanog, have the capability
      to differentiate in tenocytes. These differentiated cells express tendon-related
      markers including tenomodulin and decorin. Moreover we show that the same BM-MSCs
      can differentiate in osteocytes, as confirmed by alkaline phosphatase and von
      Kossa staining. CONCLUSION: As MSCs represent an attractive tool for tendon
      tissue repair strategies, our data suggest that bone marrow should be considered
      the preferred MSC source for therapeutic approaches.

PMID- 19383181
TI  - The challenge of making cost-effective asthma therapy available.

PMID- 19383182
TI  - World asthma day, 5 may 2009.

PMID- 19383180
TI  - What do we mean by "socialization to the model"? A Delphi study.
AB  - BACKGROUND: The term "socialization to the model" is frequently used in the
      Cognitive Behavioural Therapy (CBT) literature, but it is unclear exactly what
      constitutes socialization to the model and there is a paucity of research in this
      area. AIMS: This study aimed to develop a working definition of "socialization to
      the model". METHOD: A three-round electronic Delphi technique was used to
      generate data and to achieve a consensus agreement amongst a panel of experts (N
      = 9) in response to two questions pertaining to what constitutes "socialization
      to the model". RESULTS: All elements generated in response to the primary
      question at the first round were retained throughout and scored an IQR of <or=1
      at the final round, indicating a consensus that all elements were either
      essential or important to accurately defining socialization to the model. The
      panel also reached a consensus on five elements considered to be "indicators" of
      socialization to the model, the secondary question. CONCLUSIONS: A working
      definition of socialization to the model is presented and discussed. This
      definition has implications for both clinical practice and research.

PMID- 19383183
TI  - World No Tobacco Day: a picture paints a thousand words.

PMID- 19383184
TI  - Reporting on multidrug-resistant tuberculosis: a proposed definition for the
      treatment outcome 'failed'.

PMID- 19383185
TI  - Informed patient consent for defaulter tracing: should we obtain it?
AB  - Active default tracing is an integral part of tuberculosis (TB) programmatic
      control. It can be differentiated into the tracing of defaulters (patients not
      seen at the clinic for > or =2 months) and 'late patients' (late for their
      scheduled appointments). Tracing is carried out to obtain reliable information
      about who has truly died, transferred out or stopped treatment, and, if possible,
      to persuade those who have stopped treatment to resume. This is important
      because, unlike routine care for non-communicable diseases, TB has the potential
      for transmission to other members of the community, and therefore presents the
      issue of the rights of the individual over the rights of the community. For this
      reason, default or 'late patient' tracing (defined together as default tracing in
      this article) has been incorporated into standard practice in most TB programmes
      and, in many industrialised countries, it is also a part of public health
      legislation. In resource-poor countries with limited access to phones or e-mails,
      default tracing involves active home visits. In this Unresolved Issues article,
      we discuss the need for patient consent within both the programmatic and the
      research context; we describe how this subject arose during operational research
      training at the Research Institute of Tuberculosis in Japan; we provide comments
      from individuals who are experienced and skilled at international and national TB
      control; and finally we offer some conclusions about the way forward. This is not
      an easy subject, and we welcome open debate on the issue.

PMID- 19383186
TI  - Response to 'Informed patient consent for defaulter tracing: should we obtain
      it?'.

PMID- 19383187
TI  - How research can help control tuberculosis.
AB  - Tuberculosis (TB) has played a central role in the history of biomedical science
      from Koch onwards. Research in the nineteenth and twentieth centuries yielded
      extremely valuable diagnostic, therapeutic and preventive tools for the control
      of TB. Following the development of short-course chemotherapy in the 1970s and
      1980s, research into TB virtually evaporated. Despite the availability of an
      array of tools, TB control faltered, and the disease remains a major killer. The
      failure of the fruits of scientific research to control TB is a result of the
      shortcomings of the tools themselves as well the inadequate application of the
      tools in populations burdened by TB. A changing epidemiologic situation, with
      escalating rates of human immunodeficiency virus-related TB and the emergence of
      multidrug-resistant TB, further threatens global TB control. A robust TB research
      enterprise will be required to meet the global goals for controlling TB in the
      twenty-first century. Basic research is needed to better understand its
      pathogenesis and immunology, and to identify targets for diagnostics, drugs and
      vaccines. Research into better biomedical tools to detect, treat and prevent TB
      is also a major priority, as all of the existing tools have important
      shortcomings. In addition, research into understanding how to apply both existing
      and new tools to control TB at the population level is urgently needed. Global
      funding for TB research, $483 million in 2007, is slowly growing but is far
      behind need. To meet the ambitious goals of the Global Plan to Stop TB and the
      Millennium Development Goals, a massive investment in research will be necessary.

PMID- 19383188
TI  - Targeting human macrophages for enhanced killing of intracellular XDR-TB and MDR
      TB.
AB  - Although many compounds have been described to inhibit the replication of drug
      susceptible and drug-resistant strains of Mycobacterium tuberculosis, most of
      these studies only evaluate their in vitro activity. There is a lack of studies
      that show whether any of these agents can kill these organisms at the site where
      they normally reside post infection, namely, the macrophage of the lung
      parenchyma. It is the aim of this mini-review to identify agents that have been
      shown to enhance the killing of intracellular drug-susceptible, multidrug
      resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB)
      strains by non-killing macrophages. Because these agents appear to promote their
      activity by affecting the transport of K(+) and Ca(2+) from the phagolysosome
      containing the bacteria, and thereby promoting its acidification and activation
      of hydrolases that will eventually kill the organism, the authors suggest that
      compounds that are known to affect the transport of K(+) and Ca(2+) should be
      considered for possible activity against intracellular MDR- and XDR-TB.

PMID- 19383189
TI  - Availability, price and affordability of asthma medicines in five Indian states.
AB  - SETTING: States of Haryana, Karnataka, Maharashtra and Rajasthan, and Chennai
      (capital of Tamil Nadu State), India. OBJECTIVE: To assess the availability,
      price and affordability of beclomethasone and salbutamol inhalers in five Indian
      states using a standardised methodology. DESIGN: Data on the availability and
      price of two essential medicines for asthma, beclomethasone (50 microg/dose) and
      salbutamol (0.1 mg/dose) inhalers, were collated from five medicine price studies
      on essential medicines. RESULTS: Beclomethasone and salbutamol inhalers were
      available in 25% and 30% of public facilities in Rajasthan State only. The
      procurement price for beclomethasone and salbutamol was respectively 0.74 and
      0.56 times the international reference price (IRP). The availability of
      beclomethasone inhalers was poor in the private sector (10-65%) in four states.
      The availability of salbutamol inhalers ranged from 20% to 95% as an innovator
      brand and 83% to 100% as the generic. The price of beclomethasone was 0.87-1.49
      times the IRP, while salbutamol cost 0.82-1.12 times the IRP. Purchasing one
      inhaler each of salbutamol and beclomethasone cost between 1.6 and 2.3 days'
      wages for the lowest paid government worker. Eighty per cent of the population
      earn less than this wage. CONCLUSIONS: Essential inhalation medicines for asthma
      were not available in the public sector where low-income populations receive
      treatment. Steroid inhalers were not readily available in the private sector.
      Essential inhalation medicines for asthma are not affordable for the majority of
      the population.

PMID- 19383190
TI  - Health-related quality of life among Koreans with chronic respiratory disease.
AB  - OBJECTIVE: To evaluate the health-related quality of life (HRQoL) and to identify
      physiological and psychosocial variables predicting the HRQoL among Korean people
      with chronic respiratory disease (CRD). DESIGN: A cross-sectional correlation
      study was done with a convenience sample of 112 participants (aged 62.9 +/- 12.9
      years, forced expiratory volume in 1 second [FEV(1)%] predicted = 52.3 +/- 20.2)
      from the out-patient respiratory clinic of a large university hospital in Korea.
      HRQoL was measured using the chronic respiratory disease questionnaire (CRDQ). To
      identify the influencing factors, physiological (lung function, dyspnoea, symptom
      experience and exercise performance) and psychological (mood states and self
      efficacy) variables were examined using path analysis. RESULTS: Participants had
      a moderate level of HRQoL, with the lowest scores in CRDQ-fatigue (3.3 +/- 1.3)
      and the highest in CRDQ-mastery (5.2 +/- 1.0). Anxiety and a depressive mood
      state (-0.38) exerted the highest influence on HRQoL, followed by self-efficacy
      (0.36), dyspnoea (-0.27), exercise performance (0.22) and respiratory symptoms (
      0.17). CONCLUSION: Our findings emphasise the importance of a multidimensional
      therapeutic approach to improve HRQoL. Comprehensive interventions, including
      enhanced exercise performance, self-efficacy and symptom management, should be
      considered to improve HRQoL in Koreans with CRD.

PMID- 19383191
TI  - Oxygen for treatment of severe pneumonia in The Gambia, West Africa: a
      situational analysis.
AB  - SETTING: Health facilities in The Gambia, West Africa. OBJECTIVES: Oxygen
      treatment is vital in pneumonia, the leading cause of death in children globally.
      There are shortages of oxygen in developing countries, but little information is
      available on the extent of the problem. We assessed national oxygen availability
      and use in The Gambia, a sub-Saharan African country. METHODS: A government-led
      team visited 12 health facilities in The Gambia. A modified World Health
      Organization assessment tool was used to determine oxygen requirements, current
      provision and capacity to support effective oxygen use. RESULTS: Eleven of the 12
      facilities managed severe pneumonia. Oxygen was reliable in three facilities.
      Requirement and supply were often mismatched. Both oxygen concentrators and
      oxygen cylinders were used. Suboptimal electricity and maintenance made using
      concentrators difficult, while logistical problems and cost hampered cylinder
      use. Children were usually triaged by trained nurses who reported lack of
      training in oxygen use. Oxygen was given typically by nasal prongs; pulse
      oximetry was available in two facilities. CONCLUSIONS: National data showed that
      oxygen availability did not meet needs in most Gambian health facilities.
      Remedial options must be carefully assessed for real costs, reliability and site
      by-site usability. Training is needed to support oxygen use and equipment
      maintenance.

PMID- 19383192
TI  - Survival and predictors of outcomes in non-HIV-infected patients with extensively
      drug-resistant tuberculosis.
AB  - SETTING: A tuberculosis (TB) referral hospital in South Korea. OBJECTIVE: To
      evaluate predictors of treatment outcomes and survival among non-human
      immunodeficiency virus (HIV) infected patients with extensively drug-resistant TB
      (XDR-TB). DESIGN: Patients who were diagnosed with XDR-TB at the National Masan
      Tuberculosis Hospital from January 2001 to December 2005 were included in this
      study. We conducted a retrospective review of their medical records and mortality
      data. RESULTS: A total of 176 non-HIV-infected patients with XDR-TB were
      included. TB-related mortality was 48% (84/176), and the median survival time
      from the diagnosis date of XDR-TB was 51 months (range 0-127, 95%CI 32.53-69.47).
      Cure and treatment completion were classified as favourable outcome and treatment
      failure, death during treatment and default as poor outcome. Previous TB
      treatment with second-line drugs (aOR 2.76, 95%CI 1.02-7.44) and cavitary disease
      (aOR 3.01, 95%CI 1.12-8.08) were independent risk factors for poor outcome. Use
      of linezolid (aOR 0.10, 95%CI 0.01-0.69) and surgical resection (aOR 0.18, 95%CI
      0.04-0.78) were associated with favourable outcome. CONCLUSION: There was high
      mortality in non-HIV-infected patients with XDR-TB at a TB referral hospital in
      South Korea. Adjunctive surgical treatment and linezolid improved the outcome for
      selected patients with XDR-TB.

PMID- 19383193
TI  - Glutaraldehyde test for rapid diagnosis of pulmonary tuberculosis.
AB  - OBJECTIVE: To determine the diagnostic value of blood glutaraldehyde gelification
      time in pulmonary tuberculosis (PTB). DESIGN: We analysed the blood gelification
      time using 2.5% glutaraldehyde in 83 PTB patients, 46 patients with non
      tuberculosis pulmonary disease and 43 healthy subjects. RESULTS: The mean
      gelification time of PTB patients (556.9 +/- 122.4) is significantly less than
      non-tuberculosis pulmonary disease (708.0 +/- 100.5) and healthy subjects (821.2
      +/- 138.3; P < 0.0001). The optimum cut-off point was 615 seconds by receiver
      operating characteristic curve analysis. The sensitivity, specificity, positive
      predictive value and negative predictive value were respectively 85.5%, 89.1%,
      93.4% and 77.3% in distinguishing TB from non-PTB patients; and respectively
      85.5%, 93.3%, 92.2% and 87.4% in distinguishing PTB patients from controls (non
      PTB patients and healthy subjects). CONCLUSION: Because many centres lack sputum
      culture capacity and sophisticated radiology facilities, the glutaraldehyde test
      in conjunction with other conventional methods of diagnosis (sputum smear for
      acid-fast bacilli and frontal chest X-ray) could be a rapid, easy, cost-effective
      and reliable test for the diagnosis of PTB.

PMID- 19383194
TI  - External quality assessment of sputum smear microscopy in Taiwan.
AB  - OBJECTIVE: To evaluate the quality of sputum smear microscopy in nine Taiwan
      Centers for Disease Control contract laboratories, an external quality assessment
      (EQA) programme has been implemented since 2005. DESIGN: A sampling strategy
      based on the lot quality assurance system was applied to select slides for
      rechecking. Supervisory visits and technical training were conducted to determine
      the causes of errors and to take corrective action. RESULTS: Of the 1017 slides
      sampled in 2005, 637 (63%) had proper smear size, 492 (48%) proper thickness and
      884 (87%) proper staining; the corresponding figures were 972 (100%), 748 (77%)
      and 809 (99.6%) for the 972 slides rechecked in 2006. After training, the quality
      of size and staining of smear preparation had significantly improved (P < 0.001)
      in 2006. Rechecking of 981 readable slides in 2005 identified 3 (0.3%) high false
      negatives, 3 (16.7%) low false-positives and 26 (2.8%) low false-negatives; the
      corresponding errors were 3 (0.3%), 8 (28.6%) and 12 (1.3%) for the 972 slides
      rechecked in 2006. Of the eight laboratories, two (25%) and four (50%) reached
      80% sensitivity in 2005 and 2006, respectively. CONCLUSION: Technical training
      and EQA improved the quality of sputum smear microscopy services.

PMID- 19383195
TI  - Sputum, sex and scanty smears: new case definition may reduce sex disparities in
      smear-positive tuberculosis.
AB  - SETTING: Urban clinic, Nairobi. OBJECTIVES: To evaluate the impact of specimen
      quality and different smear-positive tuberculosis (TB) case (SPC) definitions on
      SPC detection by sex. DESIGN: Prospective study among TB suspects. RESULTS: A
      total of 695 patients were recruited: 644 produced > or =1 specimen for
      microscopy. The male/female sex ratio was 0.8. There were no significant
      differences in numbers of men and women submitting three specimens (274/314 vs.
      339/380, P = 0.43). Significantly more men than women produced a set of three
      'good' quality specimens (175/274 vs. 182/339, P = 0.01). Lowering thresholds for
      definitions to include scanty smears resulted in increases in SPC detection in
      both sexes; the increase was significantly higher for women. The revised World
      Health Organization (WHO) case definition was associated with the highest
      detection rates in women. When analysis was restricted only to patients
      submitting 'good' quality specimen sets, the difference in detection between
      sexes was on the threshold for significance (P = 0.05). CONCLUSIONS: Higher SPC
      notification rates in men are commonly reported by TB control programmes. The
      revised WHO SPC definition may reduce sex disparities in notification. This
      should be considered when evaluating other interventions aimed at reducing these.
      Further study is required on the effects of the human immuno-deficiency virus and
      instructed specimen collection on sex-specific impact of new SPC definition.

PMID- 19383196
TI  - Risk factors for extra-pulmonary tuberculosis compared to pulmonary tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB) continues to be a major global health problem.
      Extra-pulmonary TB (EPTB) manifests with protean symptoms, and establishing a
      diagnosis is more difficult than pulmonary TB (PTB). SETTING: A university
      affiliated hospital in southern Taiwan. OBJECTIVE: To analyse the risk factors
      for EPTB compared with PTB. DESIGN: This retrospective study compared patients
      with EPTB and PTB in southern Taiwan by analysing their demographic data and
      clinical underlying diseases. Risk factors for EPTB were further analysed.
      RESULTS: A total of 766 TB patients were enrolled in this study, with 102 (13.3%)
      EPTB and 664 (86.7%) PTB cases. Of the 766 patients, 3% of PTB patients had EPTB,
      while 19.6% of EPTB patients also had PTB. The most frequently involved EPTB site
      was the bone and joints (24.5%). The incidence of EPTB vs. PTB decreased
      significantly for each decade increase in patient age. Multivariate logistic
      regression analysis showed that being female, not being diabetic, having end
      stage renal disease and not smoking were independent risk factors for EPTB.
      CONCLUSION: This study defines the risk factors for EPTB compared with PTB.
      Awareness of these factors is essential for physicians to have a high index of
      suspicion for accurate and timely diagnosis.

PMID- 19383198
TI  - Combined use of QuantiFERON-TB Gold assay and chest computed tomography in a
      tuberculosis outbreak.
AB  - OBJECTIVE: To evaluate the value of the QuantiFERON-TB Gold (QFT-G) assay and
      chest computed tomography (CT), in addition to the conventional use of the
      tuberculin skin test (TST) and chest radiography (CXR), in a contact
      investigation of a tuberculosis (TB) outbreak. DESIGN: In a contact investigation
      of a TB outbreak in a high school, TST and CXR were performed on all 1044
      employees and students. QFT-G was performed on TST-positive subjects, and CT on
      QFT-G-positive subjects and students with TST > or =20 mm. RESULTS: TST was
      positive in 388 subjects (37.2%), while QFT-G was positive in 7.6% (30/394). CXR
      showed abnormal findings suggestive of TB in 10 (1.0%) subjects, all of whom were
      TST-positive and six of whom were QFT-G-positive. Findings suggestive of active
      TB were noted in 17 (32.7%) of 52 subjects by CT. Collectively, among 21 (1.1%)
      TB patients, all were TST-positive, 12 (57.1%) were QFT-G-positive and active TB
      was diagnosed by CT, and not by CXR, in 11 subjects. CONCLUSION: Compared to the
      conventional approach, the additional use of QFT-G in TST-positive subjects and
      chest CT in subgroups with a high probability of infection was found to be more
      effective in the differentiation between active TB, latent TB and non-infected
      subjects in a contact investigation.

PMID- 19383197
TI  - High prevalence of latent tuberculosis infection among injection drug users in
      Tijuana, Mexico.
AB  - BACKGROUND: We studied prevalence and correlates of latent tuberculosis infection
      (LTBI) among injection drug users (IDUs) in Tijuana, Mexico, where tuberculosis
      (TB) is endemic. METHODS: IDUs aged > or =18 years were recruited via respondent
      driven sampling (RDS) and underwent standardized interviews, human
      immunodeficiency virus (HIV) antibody testing and LTBI screening using Quanti
      FERON((R))-TB Gold In-Tube, a whole-blood interferon-gamma release assay (IGRA).
      LTBI prevalence was estimated and correlates were identified using RDS-weighted
      logistic regression. RESULTS: Of 1020 IDUs, 681 (67%) tested IGRA-positive and 44
      (4%) tested HIV-positive. Mean age was 37 years, 88% were male and 98% were
      Mexican-born. IGRA positivity was associated with recruitment nearest the US
      border (aOR 1.64, 95%CI 1.09-2.48), increasing years of injection (aOR 1.20/5
      years, 95%CI 1.07-1.34), and years lived in Tijuana (aOR 1.10/5 years, 95%CI 1.03
      1.18). Speaking some English (aOR 0.38, 95%CI 0.25-0.57) and injecting most often
      at home in the past 6 months (aOR 0.68, 95%CI 0.45-0.99) were inversely
      associated with IGRA positivity. DISCUSSION: Increased LTBI prevalence among IDUs
      in Tijuana appears to be associated with greater drug involvement. Given the high
      risk for HIV infection among Tijuana's IDUs, interventions are urgently needed to
      prevent HIV infection and treat LTBI among IDUs before these epidemics collide.

PMID- 19383199
TI  - The risk of occupational tuberculosis in Serbian health care workers.
AB  - SETTING: Health care workers in the Clinical Center of Serbia. OBJECTIVE: To
      evaluate tuberculosis (TB) incidence by job category comparing the rates of TB in
      health care workers (HCWs) working in pulmonary departments, other (non
      pulmonary) departments, and in the general population in Serbia. DESIGN:
      Prospective cohort study from 1992 to 2004. Assessment of the relationship
      between employment in different departments and TB incidence was expressed by
      relative risk (RR), which was calculated using the annual TB incidence in the
      population of Serbia as the baseline rate. RESULTS: A total of 24 HCWs developed
      active TB in the study period. The mean incidence rate was 413.2 per 100000
      persons (RR = 12.2) for hospital staff in the pulmonary department and
      20.3/100000 (RR = 0.6) for other departments. Nurses and technicians were at 7.8
      times higher risk of developing TB than doctors. The mean working period before
      the onset of illness was 15.1 years (95%CI 5.1-25.1) for HCWs in pulmonary
      departments and 8.1 years (95%CI 4.6-11.6) in non-pulmonary departments (P =
      0.006). CONCLUSION: This study indicates that HCWs were at an increased risk of
      TB, most likely from nosocomial transmission in high-risk departments.

PMID- 19383200
TI  - The impact of immigration on tuberculosis rates in the United Kingdom compared
      with other European countries.
AB  - OBJECTIVE: To investigate whether trends in tuberculosis (TB) rates across Europe
      are linked to patterns of migration. DESIGN: Descriptive analysis of Organisation
      for Economic Co-operation and Development population statistics and EuroTB data
      for 21 European countries for 1996-2005. RESULTS: TB notification rates increased
      in only three of the 21 countries: the United Kingdom, Norway and Sweden. In all
      three countries, approximately three quarters of cases were foreign-born. The UK
      had the third highest number of foreign nationals overall, but the highest number
      from a country with a TB incidence > or =250 cases/100000 (219000, 13%). European
      countries with declining TB rates had varying patterns of migration, but did not
      generally receive migrants from very high-incidence countries and/or had a
      smaller proportion of their total TB cases in their migrant population.
      CONCLUSIONS: The increase in the rate of TB in the UK, which contrasts with most
      other European countries, may, at least in part, be due to the fact that a high
      proportion of UK cases occur in the foreign-born, coupled with a comparatively
      large number of foreign nationals from countries with a very high incidence of
      TB.

PMID- 19383201
TI  - Primary and secondary tuberculosis preventive treatment in HIV clinics:
      simulating alternative strategies.
AB  - BACKGROUND: Isoniazid preventive treatment (IPT) has been recommended for human
      immunodeficiency virus (HIV) infected individuals. OBJECTIVE/DESIGN: We used a
      mathematical model to simulate the benefits and risks of preventive treatment
      delivered through antiretroviral (ARV) clinics using clinical data from Botswana.
      RESULTS: Preventive treatment was found to reduce the incidence of tuberculosis
      (TB) by at least 12 cases per 100000 population per year versus the scenario
      without such treatment over a 50-year simulation. Isoniazid (INH) resistant TB
      was observed to increase by <1% per year, even when using pessimistic assumptions
      about resistance emergence. The use of tuberculin skin testing had little impact
      as a screening procedure, while secondary treatment was observed to nearly double
      the impact of a preventive treatment program. Regardless of whether or not
      preventive treatment was implemented, INH-resistant TB rose in the context of
      increasing HIV prevalence, but was minimally amplified by preventive treatment
      itself. CONCLUSIONS: IPT programs implemented through ARV clinics may be
      effective at reducing TB incidence. The resistance contribution of IPT appears
      unlikely to supersede its overall incidence and mortality benefits.

PMID- 19383202
TI  - Clinical diagnosis of tuberculosis by specialists and non-specialists.
AB  - In resource-limited settings, tuberculosis (TB) is often diagnosed by non
      physicians using the acid-fast bacilli (AFB) smear only. This study examines the
      diagnostic accuracy of various clinicians using patient-risk history, radiography
      and AFB smear. A total of 321 physicians, nurses and medical students evaluated
      22 profiles of TB suspects and quantified their clinical suspicion (1-99%).
      Culture results determined diagnostic accuracy. Overall, high-level physician
      training may not be required; nurses working on TB, given radiograph readings,
      were as accurate as TB physicians and more accurate than other physicians and
      clinicians. By considering clinical findings with smear results, TB specialists
      were significantly more accurate than smear results alone.

PMID- 19383203
TI  - Discordant tuberculin skin and interferon-gamma tests during contact
      investigations: a dilemma for tuberculosis controllers.
AB  - Current recommendations conflict over the appropriate use of interferon-gamma
      whole blood assays to screen for tuberculosis (TB) infection in contact
      investigations. We report here on a worksite TB contact investigation in which
      tuberculin skin test (TST) and QuantiFERON-TB Gold (QFT-G) were both used to
      identify infection among 61 co-workers. Of the 27 (44%) who had a TST > or =15
      mm, 11 (41%) had negative QFT-G, raising concerns that QFT-G may not be
      sufficiently sensitive when used alone in contact investigations. The
      questionable performance of QFT-G in this setting is not unexpected, as the
      negative predictive value of a test decreases with increasing prevalence.

PMID- 19383204
TI  - Reactive nitrogen intermediate susceptibility of Mycobacterium tuberculosis
      genotypes in an urban setting.
AB  - BACKGROUND: Mycobacterium tuberculosis genotypes resistant to reactive nitrogen
      intermediates (RNI) predominate in certain urban communities, suggesting that
      this phenotype influences disease transmission. OBJECTIVE: To compare different
      M. tuberculosis genotypes for resistance to RNI generated in vitro. DESIGN: We
      genotyped 420 M. tuberculosis isolates from a neighborhood in Sao Paulo, Brazil,
      and analyzed them for susceptibility to RNI generated in acidified sodium nitrite
      (ASN) solution. RESULTS: Seventy-one (43%) of 167 recent-infection strains and 68
      (43%) of 158 endogenous infection strains showed moderate- to high-level ASN
      resistance. CONCLUSION: ASN resistance of M. tuberculosis is not necessarily a
      determining factor for enhanced transmission.

PMID- 19383205
TI  - XDR, XDR burning bright.

PMID- 19383206
TI  - The infectiousness of laryngeal tuberculosis.

PMID- 19383208
TI  - Intellectual property rights and research disclosure in the university
      environment: preserving the commercialization option and optimizing market
      interest.
AB  - Clinical and basic scientists at academic medical and biomedical research
      institutions often form ideas that could have both monetary and human health
      benefits if developed and applied to improvement of human wellbeing. However,
      such ideas lose much of their potential value in both regards if they are
      disclosed in traditional knowledge-sharing forums such as abstracts, posters, and
      oral presentations at research meetings. Learning the basics about intellectual
      property protection and obtaining professional guidance in the management of
      intellectual property from a knowledgeable technology management professional or
      intellectual property attorney can avoid such losses yet pose a minimal burden of
      confidentiality on the investigator. Knowing how to successfully navigate the
      early stages of intellectual property protection can greatly increase the
      likelihood that discoveries and knowledge will become available for the public
      good without diminishing the important mandate of disseminating knowledge through
      traditional knowledge-sharing forums.

PMID- 19383209
TI  - Dietary ammonium chloride for the acidification of mouse urine.
AB  - A novel therapeutic compound was found to induce bladder tumors in male rats.
      Given the location of the tumors and the increased amounts of calcium- and
      magnesium-containing solids found in the urine of treated animals, we
      hypothesized that tumorigenesis was secondary to urine crystal formation rather
      than a direct effect of the drug on urothelium. To investigate the basis for the
      response, a method of acidifying rodent urine was needed. This study tested the
      efficacy of 1% dietary NH(4)Cl in reducing the urinary pH of male mice. After 1
      wk, urinary pH (mean +/- SD) at 1 h after light onset was 7.51 +/- 0.32 among
      controls compared with 6.21 +/- 0.31 for the NH(4)Cl-fed group. After 2 wk of
      supplementation, urinary pH was 7.78 +/- 0.41 for controls and 6.20 +/- 0.30 for
      the NH(4)Cl-fed group. To investigate whether the time of collection altered
      urinary pH, samples also were collected 8 h after the start of the light cycle on
      the day of the 2-wk collection. Urinary pH was 7.12 +/- 0.28 for the control
      group and 5.80 +/- 0.23 for the NH(4)Cl-fed mice. The pH differences between
      control and NH(4)Cl-fed groups and the differences in pH within groups at 1 and 8
      h were statistically significant. Dietary NH(4)Cl is an effective urinary
      acidifier for mice. When evaluating the pH of mouse urine, care should be taken
      to compare samples collected at the same time after the start of the light cycle.

PMID- 19383210
TI  - Magnetic resonance imaging of acute injury in rats and the effects of
      buprenorphine on limb volume.
AB  - The purposes of this study were to determine 1) whether magnetic resonance
      imaging (MRI)-based T2 mapping and measurements of limb volume can differentiate
      injured and uninjured tissue after blunt trauma to rat hindlimbs and 2) whether
      administration of buprenorphine influences these assessments. Male Wistar rats
      (age, 3 to 4 mo) underwent blunt contusion injury to the posterior aspect of the
      hindlimb; MRI was conducted at 6, 12, 24, 48, 72, and 96 h after injury. The
      imaging results showed that administration of buprenorphine had no effect on the
      T2 value {area under the receiver operating characteristic [ROC] curve: with
      drug, 0.869 [95% confidence interval (CI), 0.78 to 0.96]; without drug, 0.809
      [95% CI, 0.72 to 0.90]} but did influence limb volume [area under the ROC curve;
      without drug, 0.954 (95% CI, 0.92 to 0.99); with drug, 0.713 (95% CI, 0.61 to
      0.82)]. When using MRI to determine the extent of injury or to track injury over
      time, calculated limb volumes may lose sensitivity to detect injury, due to the
      intrinsic increase in volume from morphine-derived drugs. During administration
      of morphine derivatives, T2 maps may provide more accurate assessments of muscle
      tissue injury both initially after injury and over time.

PMID- 19383211
TI  - A flow cytometric method for determination of the blood neutrophil fraction in
      rats.
AB  - Determination of the proportion of neutrophils in the peripheral blood is
      important for diagnostic purposes in medicine and for evaluating new drugs in the
      pharmaceutical industry. To measure the neutrophil concentration in rat blood, a
      fast and accurate flow cytometric method was developed. Rat neutrophils were
      quantified by using primary antibodies that recognize the RP1 antigen and
      secondary antibodies conjugated with fluorescein isothiocyanate. The flow
      cytometric method was calibrated by comparing cytometric results with data from a
      manual differential count. The results obtained by these 2 methods correlated
      with a Pearson correlation coefficient of 0.91 and were in agreement according to
      subsequent statistical analysis. To confirm the usefulness of the method in
      preclinical applications, the production of neutrophils in rats was stimulated by
      pegfilgrastim. Blood samples were taken at predetermined time points, and the
      pharmacodynamic profile was determined. These results confirmed that the flow
      cytometric method for neutrophil quantification is accurate and much faster than
      the manual microscopic method. Moreover, the flow cytometric method is easy to
      use, suggesting that it could become the method of choice for preclinical
      applications.

PMID- 19383212
TI  - The effect of dividing walls, a tunnel, and restricted feeding on cardiovascular
      responses to cage change and gavage in rats (Rattus norvegicus).
AB  - Cage change and gavage are routine procedures in animal facilities, yet little is
      known about whether housing modifications change responses to these procedures.
      Telemetric activity and cardiovascular parameters were assessed in this
      experiment. BN and F344 male rats were housed in open or individually ventilated
      cages, each containing 3 rats, 1 of which had a transponder. A crossover design
      was used, in which 2 groups were given dividers made of 2 intersecting boards (1
      form contained holes loaded with food pellets; the other did not) and 1 group was
      given a rectangular tunnel. On day 8 of each 2-wk period, the cages were changed;
      on day 11, rats were gavaged. The parameters were evaluated for the first hour
      and for the following 17 h. Baseline values for each rat were subtracted from the
      corresponding response values. The presence of objects did not affect the
      responses of F344 rats to cage changing or gavage. In BN rats with IVCs, the
      presence of the plain divider modified the response to both procedures. Responses
      to procedures appeared to be dependent on both the strain and the cage object,
      thus complicating the establishment of valid general recommendations.

PMID- 19383213
TI  - Successful management of rabbit anesthesia through the use of nasotracheal
      intubation.
AB  - Although nasotracheal intubation in the rabbit has been briefly described,
      scientific assessment of the procedure has not been reported. In this report we
      describe nasotracheal intubation performed in 38 male New Zealand White rabbits
      (3.0 to 5.5 kg) used for a vascular patch study. The rabbits were placed under
      general anesthesia twice, with 2 mo between the initial and final intubations.
      Rabbits were intubated by the oral or nasotracheal route and compared. Previous
      literature dismissed nasotracheal intubation, citing the possibility of
      introducing pathogens into the lungs and the necessity of high oxygen flow rates
      (presumably greater than 3 L/min). However, no clinical signs of respiratory
      disease were noted among the study animals, nor were high oxygen flow rates
      necessary. Several key points collectively facilitated a successful procedure.
      Total relaxation was essential, modification of the classic blind approach eased
      placement, a correct approach was necessary, and our development of a unique
      method of securing the tube improved tube management. The findings suggest that
      nasotracheal intubation can be used as an easy, less traumatic method of rabbit
      intubation when compared with orotracheal intubation.

PMID- 19383214
TI  - Comparison of buprenorphine and butorphanol analgesia in the eastern red-spotted
      newt (Notophthalmus viridescens).
AB  - The experimental use of amphibian models in biomedical research increases yearly,
      but there is a paucity of reports concerning analgesic use in many of these
      species. In this study, buprenorphine given by intracoelomic injection and
      butorphanol added to the tank water were compared for analgesic effect in the
      eastern red-spotted newt after bilateral forelimb amputations. Newts undergoing
      anesthesia but not surgery and newts having surgery but not given analgesia
      postoperatively were used as control groups. Animals were tested for food
      consumption, spontaneous movement, response to tapping on the tank, response to
      being touched, and body posture. Both buprenorphine by intracoelomic injection
      and butorphanol in tank water significantly promoted resumption of normal
      behavior after bilateral surgical amputation of the forelimbs. The difference
      between analgesic treatment and no analgesic treatment was maintained until 72 h
      after surgery.

PMID- 19383215
TI  - Dose-finding study of fluoxetine and venlafaxine for the treatment of self
      injurious and stereotypic behavior in rhesus macaques (Macaca mulatta).
AB  - The short-term effects on rates and durations of self-injurious behavior and self
      directed stereotypies associated with various doses of fluoxetine (FLX) and
      venlafaxine (VEN) were examined in rhesus macaques. Adult male macaques (Macaca
      mulatta; n = 17; age, 7 to 15 y) with at least 1 episode of severe SIB within the
      past 5 y were randomized to treatment with FLX (n = 6), VEN (n = 6), or placebo
      (PLC, n = 5), administered by voluntary consumption of medication provided in
      fruit-flavored tablets. After 4-wk baseline and 4-wk placebo lead-in phases,
      doses were increased monthly for 4 mo (FLX: 0.5, 2.0, 4.0, and 8.0 mg/kg; VEN:
      2.0, 4.0, 8.0, and 16.0 mg/kg). Animals in the PLC condition received similar
      nonmedicated fruit-flavored tablets. Focal behavioral observations, plasma drug
      levels, and neurochemical data were obtained. Results indicated that rates and
      percentage time spent self-biting declined at all doses of FLX, with the greatest
      effect seen at 2.0 mg/kg. For VEN, percentage time spent self-biting was
      significantly lower only at the 4.0 mg/kg dose. Treatment-induced reductions in
      platelet serotonin and cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5HIAA)
      concentrations were substantially greater in the FLX-treated condition than in
      the VEN-treated condition. Plasma FLX and norfluoxetine levels increased with FLX
      dose; plasma levels of VEN were low and not dose-related. Fluoxetine at a dose of
      2.0 mg/kg daily was most efficacious in reducing SIB, and the observed reductions
      in platelet serotonin and CSF 5HIAA levels indicated substantial bioeffect at
      this dose. Treatment with VEN was marked by noncompliance, low bioeffect, and low
      efficacy.

PMID- 19383216
TI  - L-tryptophan and correlates of self-injurious behavior in small-eared bushbabies
      (Otolemur garnettii).
AB  - Self-injurious behavior (SIB) among captive primates is a recurring problem for
      those who manage such facilities. Its prevalence highlights the need for research
      evaluating the effectiveness of potential treatment approaches. In the present
      study, 4 wk of dietary supplementation with L-tryptophan (100 mg daily) was
      evaluated for the treatment of self-inflicted wounds in 22 small-eared
      bushbabies, a prosimian primate, with a history of SIB. The treatment
      significantly reduced stereotypy and was associated with a reduction in wound
      area and severity. In terms of physiologic measures, preexisting high levels of
      cortisol were reduced in bushbabies with SIB, whereas serotonin concentrations
      were increased after 4 wk of treatment. Results indicate that L-tryptophan as a
      dietary supplement may be a viable adjunct to standard husbandry procedures for
      animals exhibiting maladaptive behaviors such as stereotypy and SIB.

PMID- 19383217
TI  - Positive reinforcement training to enhance the voluntary movement of group-housed
      sooty mangabeys (Cercocebus atys atys).
AB  - Positive reinforcement training (PRT) has successfully been used to train diverse
      species to execute behaviors helpful in the everyday care and wellbeing of the
      animals. Because little information is available about training sooty mangabeys
      (Cercocebus atys atys), we analyzed PRT with a group of 30 adult males as they
      were trained to shift from 1 side of their enclosure to the other. Over a 4-mo
      period we conducted 57 training sessions totaling 26.5 h of training and recorded
      compliance information. During training, compliance increased from 76% of the
      animals during the first 5 training sessions to 86% of the animals shifting
      during the last 5 sessions. This result indicated progress but fell short of our
      goal of 90% compliance. After 25 training sessions, problem-solving techniques
      were applied to help the consistently noncompliant animals become more
      proficient. The techniques included reducing social stress by shifting animals so
      that noncompliant monkeys could shift into an unoccupied space, using more highly
      preferred foods, and 'jackpot'-sized reinforcement. To determine whether social
      rank affected training success, animals were categorized into high, medium, and
      low dominance groups, based on 7 h of behavioral observations. A Kruskal-Wallis
      test result indicated a significant difference in compliance according to the
      category of dominance. Although training a group this large proved challenging,
      the mangabeys cooperated more than 90% of the time during follow-up sessions. The
      training program improved efficiency in caring for the mangabeys.

PMID- 19383219
TI  - Effects of storage temperature and time on clinical biochemical parameters from
      rat serum.
AB  - Serum is often frozen and banked for analysis at a later date. This study
      assessed the stability of 17 analytes in rat serum during refrigeration at 4
      degrees C and extended storage at -20 degrees C (frost-free and nonfrost-free
      freezers) and -70 degrees C. Samples were analyzed by using an automated dry
      slide chemistry analyzer at time 0 and then stored as aliquots for analysis at
      time points including day 7, 30, 90, and 360. After 7 d of refrigeration, only
      creatine kinase activity had varied by more than 10% of the starting value.
      Freezing at -70 degrees C was clearly superior to -20 degrees C where changes
      were observed in CO(2) as early as day 30 and alanine aminotransferase as early
      as day 90. Samples stored in frost-free and nonfrost-free -20 degrees C freezers
      did not differ significantly through day 90. Factors such as storage time and
      temperature should be considered when designing any retrospective study.

PMID- 19383218
TI  - Apparatus for collection of fecal samples from undisturbed spiny mice (Acomys
      cahirinus) living in a complex social group.
AB  - Assessment of fecal glucocorticoid metabolites has become a widely used method
      for monitoring stress responses. Because most small rodents are social animals
      whose physiologic parameters are affected by social stimuli, individual housing
      may compromise these data. Nevertheless, housing rodents in families or social
      groups may be an important limitation to the experimental design. The challenge
      is to collect samples from individual rodents while avoiding stress-associated
      effects from the sampling method itself. Here we present an apparatus and
      protocol allowing routine repeated collection of an individual rodent's fresh
      fecal samples without noticeable disturbance of any of the study animals;
      continuous maintenance of studied animals in a familiar environment; group
      housing; and uninterrupted visual and olfactory communication among group members
      during sampling. The apparatus consists of 1 central and 4 lateral compartments.
      The experimental animal was allowed to enter a lateral compartment voluntarily,
      where it remained for the short (4 h) period necessary for sample collection
      before rejoining the rest of the group. Evaluations involved Egyptian spiny mice,
      a social rodent increasingly studied in laboratories. The results confirmed the
      repeatability of the assessment of baseline levels of glucocorticoid metabolites.
      Moreover, keeping the animals in our experimental apparatus did not induce any
      increase in the levels of glucocorticoid metabolites, even when isolation in the
      compartment was relatively prolonged. We interpret these results as confirmation
      that our sampling procedure allows repeated individual sampling within a nearly
      undisturbed social unit.

PMID- 19383220
TI  - Multiple roles of the p75 neurotrophin receptor in the nervous system.
AB  - The p75 neurotrophin receptor (p75NTR) is a transmembrane protein that binds
      nerve growth factor (NGF) and has multiple functions in the nervous system where
      it is expressed widely during the developmental stages of life, although
      expression decreases dramatically by adulthood. Expression of p75NTR can increase
      in pathological states related to neural cell death. p75NTR is a member of the
      tumour necrosis factor (TNF) receptor family and it consists of intracellular,
      transmembrane and extracellular domains which are different from other TNF
      receptors. Either by interacting with tropomyosin receptor kinase (Trk) receptors
      or via the independent binding of neurotrophin, p75NTR can induce neurite
      outgrowth and cellular survival or cell apoptosis through several complicated
      signal transduction pathways. Most of these signalling pathways remain to be
      elucidated. By interacting with different cellular factors, p75NTR can induce
      neuron growth cone collapse or regrowth. p75NTR is also expressed in a variety of
      glial populations. The many functions of p75NTR require further study.

PMID- 19383221
TI  - Efficacy and safety of valsartan/hydrochlorothiazide fixed-dose combination
      compared with amlodipine monotherapy as first-line therapy for mild to moderate
      hypertension.
AB  - This double-blind, active- and randomized-controlled study compared the efficacy
      and safety of a fixed-dose combination of valsartan/hydrochlorothiazide 80
      mg/12.5 mg once daily (n = 32) with amlodipine monotherapy 5 mg once daily (n =
      33) for 8 weeks in patients with mild to moderate hypertension. Non-inferiority
      of valsartan/hydrochlorothiazide to amlodipine was demonstrated by comparable
      reductions in sitting systolic blood pressure (SBP), sitting diastolic blood
      pressure (DBP), and daytime, night-time and 24-h SBP and DBP on ambulatory blood
      pressure monitoring. Between-group comparisons of adverse events and changes in
      laboratory parameters did not reach statistical significance, except for uric
      acid which showed a significant increase in the valsartan/hydrochlorothiazide
      group compared with the amlodipine group, but was still below the laboratory's
      upper limit of normal. In conclusion, the use of the fixed-dose combination of
      valsartan/hydrochlorothiazide 80 mg/12.5 mg once daily as a starting regimen in
      patients with mild to moderate hypertension was shown to have non-inferior
      efficacy and comparable safety for daily practice compared with amlodipine 5 mg
      once daily monotherapy.

PMID- 19383222
TI  - Comparison of intra-coronary cell transplantation after myocardial infarction:
      Autologous skeletal myoblasts versus bone marrow mesenchymal stem cells.
AB  - Cell transplantation promises restoration of cardiac function after myocardial
      infarction (MI). Comparison of intracoronary cell transplantation with skeletal
      myoblasts (SMs) versus bone marrow mesenchymal stem cells (BM-MSCs) was carried
      out in rabbits with MI induced by ligation of the left anterior descending
      artery. The infarction-affected artery was injected with SMs, BM-MSCs or cell
      free medium (control) 24 h post-infarction (n = 15 per group). At baseline, there
      were no differences in cardiac parameters between the groups. At 4 weeks post
      transplantation, left ventricular ejection fraction significantly improved and
      left ventricular end-diastolic diameter was significantly decreased in the cell
      treated groups compared with pre-transplantation and the control group. Engrafted
      cells were found in all of the cell-treated rabbits. The cell-treated animals had
      significantly higher numbers of neovessels compared with the control. No
      significant difference was seen between the SM and BM-MSC groups. In conclusion,
      intra-coronary transplantation of SMs and BM-MSCs induced neoangiogenesis with
      comparable enhancements of cardiac performance and reduced cardiac remodelling in
      a rabbit MI model.

PMID- 19383223
TI  - Impaired blood rheology and elevated remnant-like lipoprotein particle
      cholesterol in hypercholesterolaemic subjects.
AB  - Blood rheology, fasting serum concentrations of remnant-like lipoprotein particle
      cholesterol (RLP-C) and concentrations of other lipids were compared in 23
      hypercholesterolaemic and 69 normocholesterolaemic subjects, and the relationship
      between red blood cell (RBC) deformability and RLP-C concentrations were studied
      in a different set of six hypercholesterolaemic and six normocholesterolaemic
      subjects. Passage time of whole blood and concentrations of total cholesterol
      (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and RLP-C
      were significantly higher in hypercholesterolaemic than in normocholesterolaemic
      subjects. Passage time of whole blood correlated positively with TC, TG, LDL-C
      and RLP-C and negatively with high-density lipoprotein cholesterol. Furthermore,
      the passage time of 10% haematocrit-adjusted RBCs in phosphate-buffered saline,
      which reflects RBC deformability, correlated positively with the passage time of
      whole blood and RLP-C. Thus, hypercholesterolaemic subjects had impaired blood
      rheology and elevated RLP-C concentrations, which may be associated with the
      pathophysiology of atherosclerosis in hypercholesterolaemic subjects. Impaired
      RBC deformability may contribute to impaired blood rheology associated with
      elevated RLP-C in hypercholesterolaemic subjects.

PMID- 19383224
TI  - Oral magnesium prophylaxis provides spontaneous resumption of cardiac rhythm in
      patients undergoing cardiac surgery.
AB  - Evidence is growing that magnesium supplementation in patients undergoing cardiac
      surgery is beneficial, however the best administration route has not been
      established. Previously, we showed that intra-operative direct flush infusion of
      magnesium into the aortic root before reperfusion was effective. The present
      study compared pre-operative oral administration of magnesium for 10 days with
      intra-operative flush infusion of magnesium for spontaneous resumption of cardiac
      rhythm and ventricular fibrillation in patients undergoing cardiac surgery with
      cardiopulmonary bypass (CBP). The rate of spontaneous resumption of cardiac
      rhythm, the number of shocks required for defibrillation, the energy required for
      defibrillation and the occurrence of post-CPB ventricular tachyarrhythmias were
      not significantly different between the groups. Serum magnesium levels were
      minimally increased following administration of magnesium but were within the
      normal range at all times in both groups. Oral administration of magnesium might
      provide my oprotective effects during cardiac surgery, but larger trials with a
      greater statistical power need to be carried out in order to show this.

PMID- 19383225
TI  - The association of oxidative stress and nasal polyposis.
AB  - Many diseases are linked to damage from reactive oxygen species that occurs from
      an imbalance between reactive oxygen species and antioxidants, a condition called
      oxidative stress. Nasal polyposis is considered to be an inflammatory condition
      in nasal and paranasal sinus cavities and its aetiology is still unclear. There
      are very few data on epithelial changes in nasal polyposis and their relationship
      with free radical damage. Malondialdehyde as a major end-product of lipid
      peroxidation, and superoxide dismutase and nitric oxide as antioxidants play
      important roles in oxidative stress. In this study, the concentrations of
      malondialdehyde, superoxide dismutase and nitric oxide were compared in normal
      and nasal polyposis-affected tissue samples. Malondialdehyde levels were
      significantly higher, and superoxide dismutase and nitric oxide levels were
      significantly lower in patients with nasal polyposis compared with the control
      group. This study demonstrates that there is a strong relationship between
      oxidative stress and the pathogenesis of nasal polyposis.

PMID- 19383226
TI  - Obstructive sleep apnoea, cigarette smoking and plasma orexin-A in a sleep clinic
      cohort.
AB  - Orexin-A is a neuropeptide involved in the regulation of food intake and the
      sleep-wake cycle. This study investigated plasma orexin-A levels in a sleep
      clinic cohort, adjusting for smoking habits, in 76 participants comprising 41
      with obstructive sleep apnoea (OSA) (apnoea-hypopnoea index [AHI] 44.1 +/- 19.1
      events/h) and 35 without OSA (AHI 6.3 +/- 4.7 events/h). Plasma orexin-A levels
      were significantly lower in OSA patients (15.0 +/- 4.6 ng/ml) compared with those
      without OSA (31.4 +/- 6.5 ng/ml). In non-OSA subjects, there was no significant
      difference between never smokers and ex/current smokers in plasma orexin-A levels
      (32.9 +/- 9.5 versus 29.7 +/- 8.9 ng/ml, respectively) whereas, in the OSA sub
      group, orexin-A levels were significantly lower in never smokers than in
      ex/current smokers (4.0 +/- 1.2 versus 21.4 +/- 7.0 ng/ml). A significant inverse
      relationship was found between plasma orexin-A levels and AHI amongst never
      smokers, but there was no significant relationship amongst ex/current smokers.
      These results confirm previous studies demonstrating lower levels of plasma
      orexin-A in OSA patients and indicate that smoking may affect orexin-A levels and
      AHI.

PMID- 19383227
TI  - Differential effects of single versus double aortic clamping on myocardial
      protection during coronary bypass.
AB  - The effects of double (n = 60, group 1) versus single (n = 60, group 2) aortic
      clamping on myocardial function and protection were investigated during coronary
      artery bypass grafting using a heart-lung pump. In group 1, after opening the
      cross clamp, proximal anastomosis was completed using side clamps and, in group
      2, distal and proximal anastomosis was completed with a single clamp. Cross
      clamping time in the single-clamp patients (group 2; 77.1 min) was significantly
      higher than in the double-clamp patients (group 1; 62.9 min). Troponin T was
      significantly higher in group 2 than in group 1 h and 24 h after surgery. Post
      operative left ventricular ejection fraction decreased in both groups, but this
      was not statistically significant. Post-operative wall motion score index and
      myocardial performance index increased significantly in both groups compared with
      the pre-operative level. Overall, the double-clamp technique provided better
      myocardial protection than the single-clamp technique and neither technique
      seemed to have a negative impact on the early post-operative global functioning
      of the left ventricle, however the effect of these techniques on the global
      functioning of the left ventricle in the late postoperative period needs to be
      evaluated.

PMID- 19383228
TI  - Association between renin-angiotensin system gene polymorphism and recurrent
      wheezing in Chinese children: a 4-year follow-up study.
AB  - This study aimed to clarify the association between angiotensin-converting enzyme
      (ACE) gene polymorphisms and infant wheezing, and to determine whether an
      association may contribute to early prediction of persistent wheezing and asthma.
      The study cohort comprised 149 patients with asthma, 169 patients with wheezing
      but no clinical diagnosis of asthma and 165 healthy control subjects. The
      insertion/deletion (I/D) polymorphism of the ACE gene was determined by
      polymerase chain reaction. Total serum immunoglobulin E was determined for the
      wheezy group and a 4-year follow-up study was carried out to observe wheezing
      relapse. Significant differences were found between patients and controls in
      allele frequency and genotype distribution. The DD genotype was more frequent in
      patients in the wheezing and asthma groups than in the control subjects. Patients
      with the DD genotype had a higher frequency of relapse than patients expressing
      the ID or II genotypes. It is concluded that the DD genotype of ACE is a risk
      factor for recurrent wheezing in early childhood.

PMID- 19383229
TI  - Clinicopathological variables associated with lymph node metastasis and
      prognostic factors in pT2 gastric cancer.
AB  - This retrospective study investigated the clinicopathological variables
      associated with lymph node metastasis and prognosis in 325 patients with pT2
      gastric cancer in order to set out a foundation for the surgical management of
      this condition. Univariate and multivariate analyses identified factors that were
      predictive of lymph node metastasis. Cox regression analysis evaluated the effect
      of prognostic factors on survival. Tumour location, maximum tumour diameter,
      lymphatic invasion and total retrieved lymph nodes (tLN) were revealed as
      independent factors for lymph node metastasis in pT2a gastric cancer, whereas
      histological type, lymphatic invasion and tLN were associated with lymph node
      metastasis in patients with pT2b gastric cancer. Maximum tumour diameter,
      lymphatic invasion and metastatic lymph node (mLN) ratio, but not tLN, were
      independent prognostic factors in pT2a cancer. Maximum tumour diameter and mLN
      ratio, but not tLN, were independent prognostic factors in pT2b cancer. Overall,
      it is concluded that maximum tumour diameter and mLN ratio are important
      prognostic factors in pT2 gastric cancer.

PMID- 19383230
TI  - Prediction of functional outcome in stunned myocardium after myocardial
      infarction using BMIPP and tetrofosmin imaging.
AB  - The predictive value of combined (123)iodine-labelled 15-(p-iodophenyl)-3R,S
      methyl pentadecanoic acid imaging ((123)I-BMIPP) and early technetium-99m
      ((99m)Tc)-tetrofosmin imaging was compared with combined (123)I-BMIPP and delayed
      (99m)Tc-tetrofosmin or (123)I-BMIPP and thallium-201 ((201)Tl) imaging for
      functional outcome of stunned myocardium after acute myocardial infarction (AMI)
      in 37 patients with AMI. All patients underwent successful percutaneous coronary
      intervention with/without stenting within 24 h of symptoms. Resting (201)Tl,
      (99m)Tc-tetrofosmin and (123)I-BMIPP imaging were performed within 10 days of
      hospital admission; (99m)Tc-tetrofosmin imaging was also performed 6 months
      later. Segments were mismatched when the (123)I-BMIPP score was greater than the
      (99m)Tc-tetrofosmin or (201)Tl scores, and were matched when all scores were the
      same. Left ventricular function was estimated using wall motion score.
      Sensitivity and regional wall motion were significantly better in mismatching
      (99m)Tc-tetrofosmin-early/(123)I-BMIPP segments than mismatching (201)Tl/(123)I
      BMIPP or (99m)Tc-tetrofosmin-delayed/(123)I-BMIPP segments. It is concluded that
      mismatching of (123)I-BMIPP and early (99m)Tc-tetrofosmin uptake can predict
      improvement in wall motion of stunned myocardium better than the other two
      imaging combinations.

PMID- 19383231
TI  - Impact of cystic fibrosis transmembrane conductance regulator gene mutation on
      the occurrence of chronic pancreatitis in Japanese patients.
AB  - DNA analyses of the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene in Japanese patients with idiopathic chronic pancreatitis (ICP) were
      performed to determine the relationship between the CFTR mutation and ICP. The
      study included patients with alcoholic pancreatitis (n = 20), patients with ICP
      (n = 20) and healthy volunteers (controls; n = 110). The poly-T region in intron
      8 of the CFTR gene was analysed by direct sequencing. The CFTR coding region was
      screened using single-strand conformational polymorphism and direct sequencing.
      In the controls, frequencies of the 5T genotype and 5T allele were 4.5% and 3.6%,
      respectively. The frequency of the 5T genotype was significantly higher in the
      ICP group (20%) versus controls, but was not significantly different in alcoholic
      chronic pancreatitis patients (5%). Thus, the CFTR gene mutation, especially the
      5T genotype, appears to have some relationship to ICP prevalence in Japanese
      patients independent of cystic fibrosis.

PMID- 19383232
TI  - Human cytomegalovirus glycoprotein genotypes in the genital tract tissue of tubal
      pregnancy patients.
AB  - This study investigated human cytomegalovirus (HCMV) glycoprotein genotypes in
      the genital tract tissue of 125 tubal pregnancy patients. The HCMV glycoprotein-B
      N-terminus (gBn, 54 - 485 NT), gB endoprotease cleavage site (gBclv, 1284 - 1600
      NT) and glycoproteinH (gH, -58 - 213 NT) gene fragments were amplified by nested
      polymerase chain reaction and sequenced to identify gB and gH genotypes. Of 16
      gBn-positive samples, four were gBn1, one was gBn2 and 11 were the gBn3 genotype.
      Of 13 positive gBclv samples, seven were gBclv1, two were gBclv2 and four were
      the gBclv3 genotype. Of 20 positive gH samples, 10 were gH1, six were gH2 and
      four were a combined gH1/gH2 genotype. In 10 of the samples that were positive
      for the gBn and gBclv genotypes, the gBn and gBclv genotypes were not consistent
      (four were gBclv1-gBn3). This study showed that: (i) HCMV infection with the gB1 
      gB3 glycoprotein genotypes is present in tubal pregnancy; (ii) the gBclv and gBn
      genotypes are not strictly consistent; and (iii) intragenetic variability within
      the gB gene due to homologous recombination occurs frequently.

PMID- 19383233
TI  - Unique histological features of the left atrial posterior wall.
AB  - The left atrial posterior wall (LAPW) plays a critical role in atrial
      fibrillation, but the underlying mechanism remains unclear. In the present study,
      we sought to characterize the histological features of the LAPW. Different atrial
      regions were dissected from hearts of normal Sprague-Dawley rats and humans.
      Haematoxylin/eosin and van Gieson staining were used to analyse atrial
      cardiomyocyte arrangement and collagen distribution, respectively. Intercellular
      junctions were evaluated by transmission electron microscopy. In contrast with
      other atrial regions, the LAPW exhibited more disorganized cardiomyocytes, larger
      intercellular spaces and variable myocardial fibre arrangement. The proportion of
      collagen was significantly higher in the LAPW than in other atrial regions.
      Interestingly, desmosomes were sparse along with intercellular gaps in the LAPW.
      In summary, distinct disarrangement of cardiomyocytes and an abundance of
      collagen exist in the LAPW. The sparsity of desmosomes in the LAPW may be related
      to the heterogeneous distribution and separation of atrial myocytes.

PMID- 19383234
TI  - In vitro differentiation of human placenta-derived adherent cells into insulin
      producing cells.
AB  - This study investigated the differentiation of placenta-derived adherent cells
      (PDACs) into insulin-producing cells (IPCs). PDACs were cultured and the cells
      characterized by analysis of cell surface markers using flow cytometry. The PDACs
      were then treated with induction media containing basic fibroblast growth factor
      (bFGF) and beta-mercaptoethanol (beta-ME). After induction, the presence of IPCs
      was demonstrated using dithizone staining, and the production of functional
      insulin was confirmed using immunocytochemistry and an enzyme-linked
      immunosorbent assay. Expression of the islet-associated genes PDX-1, Insulin 1,
      Insulin 2 and Glut 2 in the induced cells was measured using a reverse
      transcription-polymerase chain reaction; PDX-1 was expressed after 7 days of
      induction and PDX-1, Insulin 1 and Insulin 2 were all detected after 14 days.
      These results suggest that the placenta could be a new source of stem cells that
      can be induced to differentiate into IPCs following treatment with media
      containing bFGF and beta-ME.

PMID- 19383235
TI  - Effects of alendronate on the proliferation and osteogenic differentiation of MG
      63 cells.
AB  - Previous studies of the direct actions of bisphosphonates on bone have mainly
      been limited to their effects on bone-resorbing osteoclasts and little is known
      about the direct effects of bisphosphonates on osteoblasts. Here we report the
      direct effects of alendronate on the proliferation and osteogenic differentiation
      of the MG-63 osteoblast-like cell line. Cell proliferation was determined with
      the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay,
      osteogenic differentiation was evaluated with an alkaline phosphatase bioassay
      and by analysis of gene expression by reverse transcription-polymerase chain
      reaction, and the extent of calcium deposition was measured using Alizarin Red S
      staining. Alendronate significantly increased cell numbers over control values,
      with the greatest effect at 10(-8) M. Alkaline phosphatase activity and gene
      expression of bone morphogenetic protein 2, type I collagen and osteocalcin were
      increased after alendronate treatment. Alendronate also stimulated calcium
      deposition. We conclude that alendronate, apart from inhibiting osteoclastic bone
      resorption, is also a promoter of osteoblast proliferation and maturation.

PMID- 19383236
TI  - Expression and correlation of hypoxia-inducible factor-1alpha, vascular
      endothelial growth factor and microvessel density in experimental rat
      hepatocarcinogenesis.
AB  - An experimental rat hepatocellular carcinoma (HCC) model was established using
      diethylnitrosamine and N-nitrosomorpholine to induce carcinogenesis in Sprague
      Dawley rats. During hepatocarcinogenesis, seven rats were sacrificed at 0, 4, 8,
      12 and 16 weeks and 10 rats were sacrificed at 20 weeks. The levels of hypoxia
      inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor
      (VEGF) protein and mRNA were examined by immunohistochemistry, Western blot and
      semi-quantitative reverse transcriptase-polymerase chain reaction at different
      stages in the rat HCC model. Twenty weeks after induction of
      hepatocarcinogenesis, the expression of HIF-1alpha and VEGF protein and mRNA
      significantly increased compared with week 0. Microvessel density (MVD) increased
      considerably once liver cancer developed. There was a significant positive
      correlation between MVD and both HIF-1alpha and VEGF, and between HIF-1alpha and
      VEGF levels. These results suggest that HIF-1alpha and VEGF play important roles
      in tumour occurrence and development during rat hepatocarcinogenesis, possibly
      through promoting tumour angiogenesis.

PMID- 19383237
TI  - Suppression of vascular endothelial growth factor (VEGF) expression by targeting
      the Bcr-Abl oncogene and protein tyrosine kinase activity in Bcr-Abl-positive
      leukaemia cells.
AB  - Studies have shown that vascular endothelial growth factor (VEGF), a major and
      potent inducer of angiogenesis, is directly triggered by the disease-related
      oncogene Bcr-Abl in Bcr-Abl-positive cells. In this study, inhibition of Bcr-Abl
      tyrosine kinase activity by imatinib significantly decreased VEGF expression in
      Bcr-Abl-positive K562 cells in vitro. Imatinib treatment in vivo of nude mice
      xenografted with K562 cells resulted in a significant reduction in tumour size
      and microvessel density compared with untreated tumours. In addition, interfering
      with Bcr-Abl oncogene expression with small interfering RNAs (siRNAs) not only
      induced a specific reduction of Bcr-Abl mRNA and protein expression, but also
      efficiently inhibited the expression of VEGF in K562 cells. Combined treatment
      with imatinib and Bcr-Abl-targeting siRNAs resulted in an enhanced effect on VEGF
      suppression in K562 cells. The combined application of Bcr-Abl-targeting siRNAs
      and imatinib may provide a potent novel therapeutic approach for chronic myeloid
      leukaemia.

PMID- 19383238
TI  - The efficacy of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125),
      carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), alpha
      fetoprotein (AFP) and human chorionic gonadotropin (hCG) levels in determining
      the malignancy of solitary pulmonary nodules.
AB  - We investigated the utility of the tumour markers carcinoembryonic antigen (CEA),
      cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carbohydrate
      antigen 15-3 (CA15-3), alpha-fetoprotein (AFP) and human chorionic gonadotropin
      (hCG) for the differential diagnosis of benign and malignant solitary pulmonary
      nodules in 42 hospitalized patients. Routine medical history and physical
      examination of each patient was performed and each patient also had a chest X-ray
      and a thoracic computed tomography scan. The following diagnostic procedures were
      also undertaken: bronchoscopy, transthoracic needle aspiration biopsy, sputum
      cytology and culture, analysis of sputum acid-fast bacilli and thoracotomy.
      Measurement of serum levels of tumour antigens by Immulite 2000 radioimmunoassay
      found that three tumour markers, CEA, CA125 and CA15-3, could be used in the
      diagnosis of malignant solitary pulmonary nodules. More research is now required
      involving a larger group of patients.

PMID- 19383239
TI  - Expression of CD34, alpha-smooth muscle actin and transforming growth factor
      beta1 in squamous intraepithelial lesions and squamous cell carcinoma of the
      cervix.
AB  - This retrospective study investigated CD34, alpha-smooth muscle actin (alpha
      SMA), and transforming growth factor-beta1 (TGF-beta1) expression in stromal
      cells of cervical intraepithelial neoplasias (CINs; n = 30), invasive cervical
      squamous cell carcinomas (SCCs; n = 38) and adjacent normal cervix. Normal cervix
      and CINs contained diffuse CD34-positive stromal cells but no alpha-SMA-positive
      myofibroblasts. In contrast, 34 of 38 SCCs were free of CD34-positive stromal
      cells and all contained alpha-SMA-positive stromal myofibroblasts; adjacent
      normal tissue contained CD34-positive stromal cells and no alpha-SMA-positive
      myofibroblasts. More intense TGF-beta1 expression was observed in SCC cells than
      in normal cervical epithelium or CINs. This study shows that the disappearance of
      CD34-positive stromal cells and appearance of alpha-SMA-positive stromal
      myofibroblasts may be associated with transformation of cervical CIN to SCC.
      These findings support the suggestion that over-production of TGF-beta1 in SCC
      cells is one potential mechanism mediating the transformation of stromal cells to
      myofibroblasts in cervical carcinogenesis.

PMID- 19383240
TI  - Axonal degeneration of nigra-striatum dopaminergic neurons induced by 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine in mice.
AB  - As one of the main pathological changes of Parkinson's disease (PD), axonal
      degeneration was thought to be a passive process that is secondary to the
      apoptosis of dopaminergic neurons and, therefore, it has been overlooked for some
      time. Recent research, however, has indicated that axonal injury is the first
      location of damage in dopaminergic neurons in PD, and that the degree of injury
      in axonal degeneration is higher than in neural death. This study explored the
      relationship between apoptosis of dopaminergic neurons and their axonal
      degeneration by observing dopaminergic neuronal injury and axonal degeneration in
      the substantia nigra-striatum in different animal PD model and control groups.
      The results show that axonal degeneration plays a crucial role in the
      pathogenesis of PD and suggest that the process of axonal degeneration occurs
      independently of apoptosis and may even induce neuronal apoptosis. Thus,
      preventing axonal degeneration may be a potential new therapeutic strategy for
      PD.

PMID- 19383241
TI  - What should be the primary treatment in atrial fibrillation: ventricular rate
      control or sinus rhythm control with long-term anticoagulation?
AB  - Recent trials have favoured ventricular rate control in atrial fibrillation (AF)
      management, however the present study investigated whether the restoration and
      maintenance of sinus rhythm with long-term anticoagulation therapy was superior
      in terms of embolic events and death in 534 patients with an AF duration > 48 h.
      Patients were randomized and received sinus rhythm control with either aspirin
      (group 1) or warfarin (group 2), or they were given ventricular rate control
      (group 3). Cardioversion to sinus rhythm was attempted in 425 patients and was
      successful in 387 (91.1%) of them. After 3 years' follow-up there were 12, two
      and 15 embolic events in groups 1, 2 and 3 respectively (significant difference
      between groups 1 and 2, and 2 and 3) and overall mortalities were four, two and
      12, respectively (significant difference between groups 2 and 3). It is concluded
      that patients with an AF duration > 48 h might benefit considerably from sinus
      rhythm restoration and long-term warfarin therapy in terms of embolic events and
      mortality.

PMID- 19383242
TI  - Experimental study of COX-2 selective and traditional non-steroidal anti
      inflammatory drugs in total hip replacement.
AB  - This study investigated the effects of non-steroidal anti-inflammatory drugs
      (NSAIDs) on peri-operative blood loss during elective total hip replacement.
      Patients were randomized to receive enteric-coated diclofenac 50 mg (n = 18),
      rofecoxib 12.5 mg (n = 17) or placebo (n = 16) administered orally three times
      daily for 2 weeks prior to surgery. Severe adverse effects resulting in
      discontinuation of trial participation occurred in six patients in the diclofenac
      group, five patients in the rofecoxib group and two patients in the placebo
      group; all drop-outs occurred at various times after surgery. Compared with
      placebo, peri-operative blood loss increased by 32% in the diclofenac group and
      by 7% in the rofecoxib group. Total mean +/- SD blood loss was 1040 +/- 136 ml in
      the diclofenac group, 844 +/- 83 ml in the rofecoxib group and 789 +/- 82 ml in
      the placebo group. Thus, administering a non-selective NSAID 2 weeks prior to
      elective total hip replacement significantly increases peri-operative blood loss.

PMID- 19383243
TI  - Radiosensitization and anti-tumour effects of cytosine deaminase and thymidine
      kinase fusion suicide gene in human adenoid cystic carcinoma cells.
AB  - Herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli cytosine
      deaminase (CD) can convert innocuous prodrugs into cytotoxic metabolites and are
      being investigated for use in gene therapy for cancer. Human adenoid cystic
      carcinoma (ACC-2) cells transduced with a CD/HSV-TK fusion gene (ACC-2/CD-TK
      cells) were found to be more sensitive to radiation than ACC-2 cells when exposed
      to 5-fluorocytosine (5-FC; 40 microg/ml) plus ganciclovir (0.1 microg/ml) for 48
      h before irradiation. Analysis of radiation survival curves for cells exposed to
      5-FC plus ganciclovir before irradiation showed that ACC-2 cells had a higher
      capacity for sublethal damage repair (D(q) value) and greater cellular
      radiosensitivity (D(0) value) than ACC-2/CD-TK cells. Colony formation rate after
      2 Gy of irradiation was significantly greater for ACC-2 than for ACC-2/CD-TK
      cells when cells were treated with 5-FC plus ganciclovir before irradiation. This
      study, therefore, indicates that addition of radiation might substantially
      improve the therapeutic potential of CD-TK fusion gene therapy of human adenoid
      cystic carcinomas.

PMID- 19383244
TI  - Endotoxin tolerance of RAW264.7 correlates with p38-dependent up-regulation of
      scavenger receptor-A.
AB  - Pre-exposure to lipopolysaccharide (LPS) leads to hyposensitivity to secondary
      LPS stimulation, known as endotoxin tolerance. The role of macrophage scavenger
      receptor-A (SR-A) in endotoxin tolerance is unknown. In this study, LPS was shown
      to induce SR-A expression in the mouse macrophage cell line, RAW264.7, in dose-
      and time-dependent manners, which correlated with inflammatory cytokine
      suppression in RAW264.7 on secondary LPS stimulation. Over-expression of SR-A in
      RAW264.7 suppressed tumour necrosis factor (TNF)-alpha release and nuclear factor
      (NF)-kappa B activation, demonstrating the involvement of SR-A in endotoxin
      tolerance. LPS-pre-treated RAW264.7 cells could bind and internalize more
      fluorescein isothiocyanate (FITC)-LPS than untreated cells and both the SR-A
      ligand, fucoidan, and anti-SR-A 2F8 antibodies completely suppressed LPS-induced
      binding and internalization of FITC-LPS by RAW264.7. LPS-induced SR-A expression
      on RAW264.7 was completely suppressed by the p38-specific inhibitor, SB203580,
      but not by inhibition of toll-like receptor 4 (TLR4) signalling with MTS510,
      demonstrating that p38- but not TLR4-dependent up-regulation of SR-A was involved
      in endotoxin tolerance through binding and internalization of LPS.

PMID- 19383245
TI  - Detection of cancer stem cells from the C6 glioma cell line.
AB  - Various malignant cancers have been found to contain a sub-population of stem
      cell-like tumour cells, or cancer stem cells (CSCs), however, culture methods for
      CSCs and the size of the fraction of CSCs in C6, which is a commonly used glioma
      cell line, remain controversial. In this study, we demonstrated that the C6 cell
      line contains a fraction of tumour cells that can form tumour spheres in a
      simplified serum-free neural stem cell medium and express CD133 and nestin, which
      are widely-used markers for brain CSCs. Immunohistochemistry and
      immunofluorescence confirmed the existence of CSCs both in the C6 cell line and
      C6 xenografts. Flow cytometry demonstrated that 4.02% of cells in the C6 cell
      line and 4.21% in the C6 xenografts presented as CSCs. These results confirm the
      fraction of CSCs in the C6 cell line and provide a simple and effective method
      for isolation of CSCs to study the initiation and progression of human glioma
      and, possibly, other malignant tumours.

PMID- 19383246
TI  - Recombinant human erythropoietin protects against experimental spinal cord trauma
      injury by regulating expression of the proteins MKP-1 and p-ERK.
AB  - The present study explored the tissue-protective effect of erythropoietin in rats
      after experimental spinal cord injury (SCI) produced by dropping a weight onto
      surgically exposed spinal cord. Sixty rats were randomized to sham operation
      (spinal cord exposure; control), SCI plus intraperitoneal saline injection, or
      SCI plus intraperitoneal erythropoietin injection. Locomotor function was
      evaluated with Basso, Beattie and Bresnahan scores 1 day (24 h) and 7 days later,
      and rats were then killed for analysis of lesion site tissue. Compared with
      saline-treated SCI rats, erythropoietin-treated SCI rats showed significantly
      less locomotor dysfunction and faster locomotor recovery. Immunohistochemistry
      showed that erythropoietin-treated SCI rats had a significantly lower phospho
      extracellular signal-regulated kinase (p-ERK) protein expression and a
      significantly higher mitogen-activated protein kinase phosphatase-1 (MKP-1)
      protein expression than saline-treated SCI rats. Haematoxylin-eosin staining
      showed progressive disruption of dorsal white matter and neuron loss after SCI;
      lesions were less severe and there was more neuron regeneration in the
      erythropoietin group than in the saline group. It is concluded that
      erythropoietin reduces pathological changes and SCI severity via down-regulation
      of p-ERK and up-regulation of MKP-1.

PMID- 19383247
TI  - The neuroprotective and anti-inflammatory effects of diltiazem in spinal cord
      ischaemia-reperfusion injury.
AB  - The protective effects of diltiazem were examined in a rabbit model of spinal
      cord ischaemia-reperfusion induced by infrarenal aortic occlusion for 30 min. In
      the diltiazem group (n = 6), an intravenous infusion (2 microg/kg per min) was
      started 10 min before ischaemia induction; normal saline solution was infused in
      the control group (n = 6). Neurological function was assessed using modified
      Tarlov criteria 24 h after surgery. Plasma samples were analysed for interleukin
      (IL)-6 and IL-10. Spinal tissue was analysed for malondialdehyde, nitric oxide
      and reduced glutathione activities. Tarlov scores of the diltiazem-treated
      rabbits indicated significantly improved hind-limb motor function compared with
      the control group. The diltiazem group also had better quantitative and
      qualitative histopathological findings. Diltiazem infusion significantly reduced
      IL-6 levels 3 and 24 h after reperfusion compared with the control group. The
      mean IL-10 level in the diltiazem group was significantly higher than in the
      control group 24 h after reperfusion. It is concluded that diltiazem has
      cytoprotective and anti-inflammatory properties, leading to reduced spinal cord
      injury.

PMID- 19383248
TI  - Exercise training and endothelial progenitor cells in haemodialysis patients.
AB  - Haemodialysis patients have few endothelial progenitor cells (EPCs) and an
      unfavourable cardiovascular outcome. The effects on peripheral blood CD34(+)
      cells and EPCs of a 6-month walking exercise programme were studied. Thirty
      dialysis patients (20 males, age 67 +/- 12 years) were prescribed exercise (two
      daily 10-min home walking sessions at moderate intensity, group E, n = 16) or not
      prescribed exercise (control, group C, n = 14). On entry and after 6 months
      peripheral blood CD34(+) cells, EPCs (assessed as CD34(+) cells co-expressing
      AC133 and vascular endothelial growth factor receptor 2 [VEGFR2], and as
      endothelial colony-forming units [e-CFU]) and exercise capacity (6-min walking
      distance, 6MWD) were evaluated. In group E, 6MWD and e-CFU increased
      significantly during the study period, with no significant changes in CD34(+) or
      CD34(+) AC133(+) VEGFR2(+) cell numbers. The change in e-CFU was directly and
      significantly correlated to patient-reported training load. Group C showed no
      significant change in any variable. In haemodialysis patients, moderate-intensity
      exercise selectively increased the number of e-CFU.

PMID- 19383249
TI  - Comparison of dual X-ray laser and dual energy X-ray absorptiometry techniques of
      osteodensitometry.
AB  - Dual X-ray laser (DXL) heel measurements of bone mineral density (BMD) and dual
      energy X-ray absorptiometry (DEXA) total hip and lumbar spine BMD measurements
      were compared for their ability to detect osteoporosis and osteopenia according
      to World Health Organization criteria. The study included 164 women aged 40 - 83
      years. DXL heel measurements were recorded for all patients and 89 of the women
      underwent DEXA. For DXL heel measurements/DEXA lumbar spine measurements, the
      relative sensitivity was 50%, relative specificity was 97% and relative
      reliability (Kappa score) was 0.55 for osteoporosis detection. For detecting
      osteoporosis or osteopenia, the relative sensitivity increased to 86% but the
      relative specificity reduced to 38% and the relative reliability was considerably
      lower (Kappa score 0.21). Although previous studies have shown DXL heel
      measurement to be a good technique in the diagnosis and assessment of
      osteoporosis based on BMD, particularly for fast, cost-effective bone scanning,
      we suggest that there are currently insufficient data to prove its use as a
      standard measurement technique for BMD.

PMID- 19383250
TI  - Evaluation of the relationship between anxiety and depression and bruxism.
AB  - This study examined the relationship between anxiety, depression and bruxism in
      99 patients with temporomandibular disorders (TMD). Patients were divided into
      two groups: 58 patients with bruxism and 41 without bruxism. Symptoms of TMD were
      evaluated according to the Craniomandibular Index. The psychological condition of
      patients was assessed using the Beck Depression Inventory (BDI), the Hospital
      Anxiety Depression Scales (HADS) and the Hamilton Anxiety Rating Scale (HAMA).
      The mean anxiety and depression scores (HADS and HAMA) for patients with bruxism
      were statistically significant higher in patients with bruxism compared with
      those without bruxism. Thus, there may be an association between bruxism and
      higher levels of anxiety and/or depression in patients with TMD.

PMID- 19383251
TI  - Microvessel density and expression of thrombospondin-1 in non-small cell lung
      cancer and their correlation with clinicopathological features.
AB  - Microvessel density and thrombospondin-1 (TSP-1) expression were analysed in 42
      non-small cell lung cancer (NSCLC) specimens and 40 normal lung tissue specimens
      using immunohistochemistry. Microvessel density was significantly higher and TSP
      1 expression significantly lower in NSCLC tissue compared with normal tissue.
      Significantly lower levels of TSP-1 expression and higher microvessel densities
      were found in late-stage NSCLC compared with early-stage NSCLC, and in those with
      lymph node metastasis compared with those without metastasis. A statistically
      significant inverse correlation was observed between TSP-1 expression and
      microvessel density in squamous cell carcinoma but not in adenocarcinoma. These
      results suggest a close relationship between microvessel density and NSCLC tumour
      progress, and that a high expression of TSP-1 may play an important role in
      inhibiting tumour occurrence and development. The lack of correlation between
      microvessel density and TSP-1 expression in adenocarcinoma suggests that the
      mechanism of tumour inhibition by TSP-1 varies according to histological type.

PMID- 19383252
TI  - Quality of life and the effect on social status among Slovenian women after
      breast cancer treatment.
AB  - This study investigated whether the type of surgical procedure used to treat
      breast cancer (mastectomy versus breast-conserving lumpectomy) had any effect on
      the quality of life and social status of women. The prospective analysis included
      382 women newly diagnosed with non-metastatic breast cancer who had undergone a
      surgical intervention for breast carcinoma at our institution: 198 patients had
      undergone mastectomy with axillary lymphadenectomy and 184 patients had undergone
      breast-conserving lumpectomy with local axillary lympha-denectomy. The post
      mastectomy women reported significantly more financial problems, a lowered social
      status and more physical symptoms compared with the breast-conserving post
      lumpectomy patients. The patients that underwent lumpectomy were more satisfied
      with their body image and their sexual life. Since the adverse financial effects
      of wage loss can significantly decrease a patient's quality of life, this study
      indicates that post-mastectomy patients in particular need to be protected more
      effectively against a decline in their social status.

PMID- 19383253
TI  - Measurement of acetabular anteversion in developmental dysplasia of the hip in
      children by two- and three-dimensional computed tomography.
AB  - This study assessed the angle of acetabular anteversion (AA) in 66 children with
      developmental dysplasia of the hip (132 hips: 24 left, 25 right, 17 bilateral and
      49 unaffected hips as controls). The AA was measured by two- and three
      dimensional computed tomography (2D-CT and 3D-CT). Measurements were taken by
      three observers and repeated 2 weeks later by one of these observers. Intra- and
      inter-observer agreement was analysed using the intra-class correlation
      coefficient. For all hips, the mean AA (+/-SD) measured by 2D-CT versus 3D-CT was
      statistically significantly different (15.76 +/- 5.23 degrees versus 16.76 +/-
      4.43 degrees , respectively). The mean (+/-SD) AA by 3D-CT in unaffected and
      affected hips was also statistically significantly different (13.92 +/- 3.95
      degrees versus 18.44 +/- 3.82 degrees , respectively). A significant positive
      correlation between age at presentation and AA was found in affected, but not
      unaffected, hips. The 3D-CT showed better intra- and inter-observer agreement
      than 2D-CT for assessing AA hence is a more reliable measurement of AA. An
      increased AA is one component of anatomical abnormalities in developmental
      dysplasia of the hip and the abnormality appears to worsen with age.

PMID- 19383254
TI  - Influence of propylthiouracil and methimazole pre-treatment on the outcome of
      iodine-131 therapy in hyperthyroid patients with Graves' disease.
AB  - There is ongoing controversy about potential differences in the influence of the
      anti-thyroid drugs propylthiouracil (PTU) and methimazole (MMI) on radioiodine
      treatment of Graves' hyperthyroidism. This retrospective study investigated the
      influence of PTU and MMI pre-treatment, individually or sequentially, on the
      outcome of iodine-131 ((131)I) therapy in 199 patients with Graves' disease who
      had been treated with (131)I for the first time and followed up at 3 and 6 months
      after treatment. Pre-treatment with PTU, or sequential PTU and MMI pre-treatment,
      increased the failure rate of (131)I therapy and reduced the rate of
      hypothyroidism. MMI pre-treatment alone had no significant influence on the
      results of (131)I therapy. Logistic regression analyses indicated that PTU pre
      treatment and having a thyroid gland of > 60 g were both significantly related to
      (131)I therapy failure.

PMID- 19383255
TI  - A very rare complication: new hair growth around healing wounds.
AB  - We present the case of a patient in whom active new hair growth occurred around a
      wound after healing. This very rare phenomenon has not previously been reported
      in the literature. We postulate that, after the epidermis and hair follicles have
      been damaged by wounding, it is possible for them naturally to heal and repair if
      provided with an appropriate chemical and physical microenvironment. This
      hypothesis may inspire new thinking in the management of alopecia, tissue
      engineering and the regeneration of other organs.

PMID- 19383256
TI  - Primary small cell carcinoma of the kidney with tumour thrombus extension into
      the inferior vena cava and pulmonary artery: a case report and review of the
      literature.
AB  - Renal small cell carcinoma is a rarely seen malignant neoplasm with high
      propensity for distant metastasis and aggressive behaviour showing combined
      characteristics of neuroendocrine and epithelial neoplasia in terms of
      immunohistochemistry and ultrastructure. To the best of our knowledge this is the
      first report of primary small cell carcinoma of the left kidney with tumour
      thrombus extending to the inferior vena cava and pulmonary artery to undergo left
      radical nephrectomy and tumour thrombectomy under extracorporeal circulation and
      deep hypothermic circulatory arrest. The patient was a 33-year old male. He was
      discharged from hospital 10 days following the procedures and remained alive at
      the time of writing, over 7 months after discharge. Light microscopy,
      immunohistochemistry and the survival outcome of this case are presented and
      these are discussed in the context of a review of similar cases in the current
      literature. This case demonstrated that, in the absence of distant metastases,
      renal small cell carcinoma with tumour thrombus does not contraindicate surgery.

PMID- 19383257
TI  - Reproductive biotechniques in buffaloes (Bubalus bubalis): status, prospects and
      challenges.
AB  - The swamp buffalo holds tremendous potential in the livestock sector in Asian and
      Mediterranean countries. Current needs are the faster multiplication of superior
      genotypes and the conservation of endangered buffalo breeds. Recent advances in
      assisted reproductive technologies, including in vitro embryo production
      methodologies, offer enormous opportunities to not only improve productivity, but
      also to use buffaloes to produce novel products for applications to human health
      and nutrition. The use of molecular genomics will undoubtedly advance these
      technologies for their large-scale application and resolve the key problems
      currently associated with advanced reproductive techniques, such as animal
      cloning, stem cell technology and transgenesis. Preliminary success in the
      application of modern reproductive technologies warrants further research at the
      cellular and molecular levels before their commercial exploitation in buffalo
      breeding programmes.

PMID- 19383258
TI  - Modulation of bovine sperm signalling pathways: correlation between intracellular
      parameters and sperm capacitation and acrosome exocytosis.
AB  - In the present study, the viability, intracellular pH (pHi), cAMP ([cAMP]i),
      calcium concentration and protein phosphotyrosine content were evaluated in
      relation to the acrosomal and capacitation status of freshly ejaculated bull
      spermatozoa. These parameters were evaluated before and after incubation with the
      capacitation inducer heparin, the phosphodiesterase inhibitor 3-isobutyl-1
      methylxanthine (IBMX), the phosphotyrosyl-protein phosphatase inhibitors
      phenylarsine oxide (PAO) and sodium orthovanadate, and hydrogen peroxide. The
      results obtained were integrated to address the physiological interactions
      between the different signalling events affecting sperm capacitation and acrosome
      reaction. As expected, heparin promoted the expression of the 'B' pattern of
      chlortetracycline binding, increased pHi, [cAMP]i and the phosphotyrosine content
      of sperm proteins. The effects of heparin were enhanced by IBMX. Both PAO and
      sodium orthovanadate stimulated protein phosphotyrosine content and acrosomal
      exocytosis, although only PAO affected pH, Ca2+ and cAMP levels. Intracellular pH
      was increased while both Ca2+ and [cAMP]i were decreased. Physiological
      concentrations of H2O2 increased [cAMP]i and promoted acrosomal exocytosis. A
      significant positive correlation was found between sperm capacitation, protein
      phosphotyrosine content and stored Ca2+ concentration, whereas the acrosome
      reaction was correlated with pHi and Ca2+ concentration. This study presents the
      first global analysis of the major elements individually described during sperm
      capacitation and acrosome reaction signalling pathways, supported by statistical
      correlations.

PMID- 19383259
TI  - Cryopreservation affects bovine sperm intracellular parameters associated with
      capacitation and acrosome exocytosis.
AB  - Although semen cryopreservation is widely and commonly used in the bovine
      breeding industry, half the spermatozoa do not survive and most of those that do
      survive undergo numerous physiological changes that affect their fertilising
      ability. The aim of the present study was to determine how cryopreservation
      affects the intracellular events involved in sperm capacitation and acrosome
      reaction. Immediately after thawing and washing, almost 50% of spermatozoa were
      capacitated and more than 20% had lost their acrosome. The sperm cAMP
      concentration was lower than that in freshly ejaculated spermatozoa, but the
      cytosolic pH (pHcyt) was in the expected range. The free cytosolic Ca2+
      concentration ([Ca2+]cyt) was higher than in fresh spermatozoa and cryopreserved
      spermatozoa had internally stored Ca2+. Phenylarsine oxide increased pHcyt and
      both cytosolic and stored Ca2+ concentrations, whereas orthovanadate enhanced
      acrosome loss and protein tyrosine phosphorylation (P-Tyr). Heparin increased the
      percentage of spermatozoa expressing the B (capacitated) chlortetracycline
      binding pattern, pHcyt, P-Tyr and Ca2+ storage. Moreover, positive correlations
      exist between capacitation, cAMP, P-Tyr and stored Ca2+, whereas the acrosome
      reaction is positively correlated with pHcyt and [Ca2+]cyt. These results
      demonstrate that sperm regulatory mechanisms may be affected by the
      cryopreservation procedure, but frozen-thawed sperm can still regulate their
      capacitation and acrosome reaction signalling pathways.

PMID- 19383261
TI  - Normal mammary gland growth and lactation capacity in pregnant relaxin-deficient
      mice.
AB  - Pups born to mice with a targeted deletion of relaxin or its receptor (Rxfp1) die
      within 24 h postpartum. This has been attributed, in part, to abnormal mammary
      gland development in relaxin-mutant mice (Rln-/-). However, mammary development
      is normal in relaxin receptor-mutant (Rxfp1-/-) mice. The present study aimed to
      verify the mammary phenotypes in late pregnant and early lactating Rln-/- mice
      and to test the hypothesis that relaxin is involved in milk protein synthesis.
      Comparisons between late pregnant and early lactating wildtype (Rln+/+) and Rln-/
      mice showed no differences in lobuloalveolar structure or ductal branching in
      the mammary gland. Mammary explants from Rln-/- mice also expressed beta-casein
      and alpha-lactalbumin in response to lactogenic hormones at a similar level to
      Rln+/+ mice, implying normal milk protein synthesis. Pregnant Rln-/- mice infused
      with relaxin for 6 days gave birth to live pups without difficulty, and 96% of
      pups survived beyond 7 days. This is in contrast with the 100% pup mortality in
      saline-treated Rln-/- mice or 3-day relaxin-treated Rln-/- mice. Pups born to
      relaxin-treated Rln-/- dams weighed significantly less than Rln+/+ pups but had
      similar growth rates as their wildtype counterparts. In summary, relaxin is not
      critical for mammary gland development or beta-casein and alpha-lactalbumin
      expression in late pregnant mice. In addition, Rln-/- dams did not need to be
      treated with relaxin postpartum for the pups to survive, suggesting that relaxin
      has no role in the maintenance of lactation in mice.

PMID- 19383260
TI  - The effects of hCG and growth factors on in vitro nuclear maturation of dog
      oocytes obtained during anoestrus.
AB  - The effects of human chorionic gonadotrophin (hCG) and a combination of growth
      factors on the developmental competence of canine oocytes during in vitro
      maturation was examined. Oocytes recovered from domestic dog ovaries at routine
      ovariectomy were cultured in a basic tissue culture medium with 0.3% BSA, 7
      microg mL(-1) progesterone and antibiotics. After the appropriate culture periods
      (up to 96 h), they were fixed and labelled by double-antibody immunofluorescence
      for tubulin and with propidium iodide for chromatin. Human chorionic
      gonadotrophin increased the proportion of oocytes resuming meiosis and reduced
      the degeneration rate. Supplementing with hCG in declining concentrations was of
      no superior benefit but the presence of a combination of growth factors (growth
      hormone, insulin-like growth factor-1, transforming growth factor-alpha and
      fibroblast growth factor) improved both the resumption of meiosis and the
      degeneration rate. No particular synergisms between pairs of growth factors could
      be demonstrated. Human chorionic gonadotrophin and growth factors together gave
      poorer results, implying that hCG inhibited the beneficial effects of the growth
      factors. A growth factor combination is the present most successful treatment,
      with 49% of total oocytes (inclusive of degenerated) recovered from anoestrous
      bitches at MI or MII by 96 h of culture. This is the highest result so far
      demonstrated for cultured dog oocytes.

PMID- 19383262
TI  - Exogenous transforming growth factor beta1 replacement and fertility in male
      Tgfb1 null mutant mice.
AB  - Analysis of Tgfb1 null mutant mice has demonstrated that the cytokine
      transforming growth factor beta1 (TGFB1) has essential non-redundant roles in
      fertility. The present study attempted to alleviate the infertility phenotype of
      Tgfb1 null mutant male mice by administration of exogenous TGFB1, either orally
      by colostrum feeding or subcutaneously by delivery of recombinant human latent
      TGFB1 (rhLTGFB1) via osmotic mini-pumps. Bovine colostrum and fresh unpasteurised
      bovine milk were found to be rich sources of TGFB1 and TGFB2; however, feeding
      Tgfb1 null mutant mice colostrum for 2 days failed to raise serum levels of
      TGFB1. Administration of rhLTGFB1 (approximately 150 microg in total) over 14
      days to Tgfb1 null mutant mice resulted in detectable TGFB1 in serum; however,
      mean levels remained 10-fold less than in Tgfb1 heterozygous mice. After 7 days
      and 14 days of rhLTGFB1 administration, serum testosterone, spontaneous non
      contact erections and mating behaviour were assessed. Despite the increased serum
      TGFB1, administration of rhLTGFB1 to Tgfb1 null mutant mice failed to improve
      these fertility parameters. It is concluded that sustained restoration of
      circulating latent TGFB1 to levels approaching the normal physiological range
      does not rescue the infertility phenotype caused by TGFB1 deficiency.
      Reproductive function in male Tgfb1 null mutant mice may not respond to systemic
      TGFB1 supplementation due to a requirement for local sources of TGFB1 at the site
      of action in the reproductive tract, or perturbed development during the neonatal
      period or puberty such that adult reproductive function is permanently impaired.

PMID- 19383263
TI  - Seminal plasma proteins protect flow-sorted ram spermatozoa from freeze-thaw
      damage.
AB  - Seminal plasma improves the functional integrity of compromised ram spermatozoa
      but has been reported to be toxic to sorted spermatozoa. The present study
      attempted to clarify this paradoxical effect and improve the functional integrity
      of spermatozoa following sorting and cryopreservation. The in vitro function of
      sorted spermatozoa (motility characteristics and membrane integrity) was examined
      after supplementation with differing concentrations and protein fractions of
      seminal plasma at various stages of the sorting and freezing process. For all
      experiments, spermatozoa (two males, n=four ejaculates per male) were processed
      through a high-speed flow cytometer before cryopreservation, thawing and
      incubation for 6 h (37 degrees C). Supplementation of crude seminal plasma (CP),
      its low molecular weight fraction (LP; <10 kDa) or protein-rich fraction (SPP;
      >10 kDa), immediately before freezing improved the functional integrity of sorted
      spermatozoa compared with no supplementation (control), whereas supplementation
      after thawing had no effect for CP and LP. The protective effect of seminal
      plasma was not altered by increasing the amount of protein supplementation. No
      toxic effect of CP, SPP or LP was evident even when supplemented at high protein
      concentrations. It is concluded that seminal plasma protein, if added to ram
      spermatozoa after sorting and before freezing, can improve post-thaw sperm
      quality and consequently the efficiency of sorting. This effect is most likely
      related to protection of the spermatozoa during freeze-thawing.

PMID- 19383264
TI  - Ovarian imaging in the mouse using ultrasound biomicroscopy (UBM): a validation
      study.
AB  - The mouse is a well accepted model for studies of human reproduction despite
      little being known about follicle dynamics in this species. Longitudinal studies
      of mouse folliculogenesis have been hampered by the lack of an appropriate
      imaging tool. Ultrasound biomicroscopy (UBM) may overcome this obstacle as it
      confers near-microscopic resolution through the use of high-frequency ultrasound
      waves. The objective of the present study was to determine whether UBM could be
      used to count and measure ovarian follicles and corpora lutea (CL) reliably in
      mice. Ovaries of 25 adult CD-1 mice were imaged using a 55-MHz transducer and
      then excised and processed for histology. Follicles and CL were counted and
      measured from digitally stored UBM cine-loops and photographed histological
      sections. Differences between techniques were assessed by Bland-Altman agreement
      analyses. Follicle counts yielded by the two techniques varied by only +/-1
      follicle when follicles ranged between 300 and 499 microm. Perfect agreement
      among counts was evident when follicles were >500 microm. The total number of CL
      was accurately estimated using UBM; however, the number of 350-699 microm CL was
      underestimated and the number of CL>or=700 microm was overestimated. In
      conclusion, UBM can be used reliably to count and measure follicles in mice.

PMID- 19383265
TI  - Plant protein hydrolysates (plant peptones) as substitutes for animal proteins in
      embryo culture medium.
AB  - The aim of the present study was to improve the sanitary quality of in vitro
      produced bovine embryos by using plant protein hydrolysates (plant peptones) as
      substitutes for animal proteins. Peptones were compared with bovine serum albumin
      (BSA) as the protein source in synthetic oviduct fluid medium and the quality of
      the resulting embryos was determined. Two batches of peptones (wheat and cotton)
      were selected on the basis of their anti-oxidant properties. When added to the
      culture medium, both peptones (at 0.56 mg mL(-1) for cotton peptone and at 0.18
      mg mL(-1) for wheat peptone) led to similar developmental and hatching rates
      compared with 4 mg mL(-1) BSA and embryos were equally resistant to freezing and
      able to elongate after transfer. Surprisingly, a significant decrease in reduced
      glutathione (GSH) content was observed when embryos were produced with plant
      peptone instead of BSA. Supplementation of the culture medium with precursors of
      GSH (cysteine and beta-mercaptoethanol) significantly increased the GSH content.
      A shift of the sex ratio towards male embryos was seen for Day 8 embryos cultured
      with wheat peptone, whereas no shift was observed for embryos cultured in the
      presence of BSA or polyvinylpyrrolidone. In conclusion, culture with plant
      peptones enables embryos to be obtained at a similar rate and of similar quality
      to that seen following the use of BSA. The use of the plant peptones increased
      the sanitary quality of the embryos and decreased the cost of embryo production.

PMID- 19383266
TI  - Changes in human placental 5alpha-reductase isoenzyme expression with advancing
      gestation: effects of fetal sex and glucocorticoid exposure.
AB  - 5alpha-reduced steroids, including allopregnanolone, suppress neuronal activity
      and can have neuroprotective effects in the fetus. 5alpha-reductases in the
      placenta may contribute precursors to brain allopregnanolone synthesis. Preterm
      birth and glucocorticoids, administered for fetal lung maturation or for maternal
      asthma, may influence reductase expression. The aims of the present study were to
      evaluate placental 5alpha-reductase isoform expression during late gestation and
      to examine fetal sex differences and the effects of glucocorticoid therapies on
      the expression of these enzymes. Expression of the two 5alpha-reductase
      isoenzymes was measured in placental samples, whereas cortisol concentrations
      were measured in cord blood, from two cohorts. The first cohort consisted of
      women who delivered preterm and received betamethasone treatment (n=41); the
      second cohort consisted of women who delivered at term and were either healthy
      controls (n=30) or asthmatics who had used glucocorticoids (n=24). Placental
      expression of both isoenzymes increased with advancing gestation and there were
      marked sex differences in levels of 5alpha-reductase I (P<0.05), but not of
      5alpha-reductase II. The expression of both enzymes was positively correlated
      with cortisol levels (P<0.05), but there was no effect of recent glucocorticoid
      exposure. These findings suggest that the preterm neonate may have lower
      developmental exposure to 5alpha-reduced steroids and may lack steroid-mediated
      neuroprotection depending on fetal sex.

PMID- 19383267
TI  - Reactive oxygen species in bovine oocyte maturation in vitro.
AB  - The role of reactive oxygen species (ROS) in the in vitro maturation (IVM) of
      oocytes remains controversial. The aim of the present study was to determine
      possible fluctuations in ROS production during bovine oocyte IVM in the presence
      of different modulators of ROS generation. Cumulus-oocyte complexes were cultured
      in medium 199 (control) in the absence or presence of 0.6 mM cysteine, 1 mM 1
      choro-2,4-dinitro benzene (CDNB), 2 microM diphenyliodonium, 0.5 mM N-nitro-L
      arginine methyl ester or 10 microM sodium nitroprusside (SNP) at 39 degrees C, in
      5% CO2 in humidified air for 22 h. In addition, the respiratory chain effectors
      potassium cyanide (KCN; 1 mM) and carbonyl cyanide m-chlorophenylhydrazone (0.42
      microM) were used. Meiotic maturation was determined by the presence of MII. ROS
      production was evaluated in denuded oocytes at different time points as the ratio
      of 2',7'-dichlorodihydrofluorescein diacetate (DCHF-DA) to fluorescein diacetate
      (FDA). ROS levels, expressed as DCHF-DA:FDA, fluctuated throughout the 22 h of
      maturation depending on the treatment applied. At 12 h incubation in the presence
      of KCN and SNP, ROS levels were increased, whereas ROS levels after 12 h in the
      presence of cysteine were reduced (P<0.05). Both CDNB and SNP impaired meiotic
      progression. The higher metabolic activity demand during bovine oocyte maturation
      coincides with a concomitant reduction in ROS generation. These results suggest
      that 12 h would be a critical point for bovine oocyte IVM because it is closely
      related to the production of ROS at this time.

PMID- 19383268
TI  - Effects of age and equine follicle-stimulating hormone (eFSH) on collection and
      viability of equine oocytes assessed by morphology and developmental competency
      after intracytoplasmic sperm injection (ICSI).
AB  - Young (4 to 9 yr) and old (>or=20 yr) mares were treated with equine follicle
      stimulating hormone (eFSH), and oocytes were collected for intracytoplasmic sperm
      injections (ICSI). Objectives were to compare: (1) number, morphology and
      developmental potential of oocytes collected from young v. old mares from cycles
      with or without exogenous eFSH and (2) oocyte morphology parameters with
      developmental competence. Oocytes were collected from preovulatory follicles 20
      to 24 h after administration of recombinant equine LH and imaged before ICSI for
      morphological measurements. After ICSI, embryo development was assessed, and late
      morulae or blastocysts were transferred into recipients' uteri. Cycles with eFSH
      treatment resulted in more follicles (1.8 v. 1.2) and more recovered oocytes (1.1
      v. 0.8) than those without eFSH. Age and eFSH treatment did not effect cleavage,
      blastocyst and pregnancy rates. Treatment with eFSH had no effect on oocyte
      morphology, but age-associated changes were observed. In old mares, zona
      pellucidae (ZP) were thinner than in young mares, and perivitelline space and
      inner ZP volume (central cavity within the ZP) were larger and associated with
      oocytes that failed to develop. These results suggest that administration of eFSH
      can increase the number of oocytes collected per cycle. Oocyte morphology
      differed with age and was associated with developmental competence.

PMID- 19383270
TI  - Enhancing our knowledge of blepharitis.

PMID- 19383271
TI  - The patient's experience of blepharitis.

PMID- 19383269
TI  - Blepharitis in the United States 2009: a survey-based perspective on prevalence
      and treatment.
AB  - ABSTRACT Like dry eye disease 15 years ago, blepharitis today is a poorly defined
      condition about which there is considerable misunderstanding. For a variety of
      reasons, there is little good data on either the prevalence of blepharitis or how
      eyecare practitioners currently treat it. The work reported herein consists of
      two recent studies: a telephone survey of a representative sample of the adult US
      population (n = 5,000) whose purpose was to discover the frequency of common
      ocular surface symptoms associated with blepharitis; and a study that queried a
      selected group of ophthalmologists (n = 120) and a similarly selected group of
      optometrists (n = 84) about the frequency of blepharitis in their practices, the
      existence comorbid conditions, and their management strategies. This data
      suggests that blepharitis symptoms are very common in the US population, with
      younger individuals reporting more, and more frequent, symptoms than older
      people, contrary to clinical dogma. Ophthalmologists and optometrists report that
      blepharitis is commonly seen in clinical practice in 37% and 47% of their
      patients, respectively, and it is widely agreed that meibomian gland dysfunction
      (MGD) is the most common cause of evaporative dry eye disease. In addition,
      management paradigms are shifting away from more traditional management with
      antibiotic ointment and warm compress therapy to prescription therapy for
      anterior and posterior blepharitis.

PMID- 19383272
TI  - The effects of blepharitis on ocular surgery.

PMID- 19383273
TI  - Controlling the ocular surface: how it's done.

PMID- 19383274
TI  - Basal, reflex, and psycho-emotional tears.

PMID- 19383275
TI  - Immunoregulation on the ocular surface: 2nd Cullen Symposium.
AB  - A one-day symposium with 20 invited participants was held to review current
      knowledge regarding immunoregulation in the ocular surface and cornea. The
      program consisted of 11 lectures on various aspects of ocular and systemic
      immunoregulation, followed by a group discussion to formulate regulatory
      pathways. The ocular surface and its secondary lymphoid tissues contain numerous
      components of the innate and adaptive immune systems, which modulate the immune
      response to suppress or prevent excessive damaging immune reactions. These
      include factors that regulate induction of the immune response (afferent loop),
      as well as effector cells and soluble factors (efferent loop). The ocular surface
      is an immunologically active mucosal site that contains numerous mechanisms to
      regulate the immune response to prevent tissue destruction and vision loss.

PMID- 19383277
TI  - Predicted phenotypes of dry eye: proposed consequences of its natural history.
AB  - This paper reviews current knowledge of the pathophysiology of dry eye and
      predicts that the clinical picture in late disease differs in both severity and
      quality from that in early disease. It is hypothesized that hybrid forms evolve,
      in which aqueous-deficient dry eye (ADDE) takes on features of evaporative dry
      eye (EDE) and vice versa. As a consequence, early and late forms may require
      different diagnostic criteria and respond to different therapeutic regimes. Tear
      hyperosmolarity plays a key role in the damage mechanism of dry eye, and ADDE is
      recognized to be a low-volume, hyperosmolar state. As ADDE advances, a
      progressive decrease in lacrimal secretion occurs, exacerbated by loss of the
      corneal reflex. This causes a decrease in tear volume, thinning of the aqueous
      tear film, and retarded spreading of the tear film lipid layer. The latter is
      hypothesized to cause an increase in evaporative water loss and an added
      evaporative component to the dry eye. Thus, in advanced disease, the hybrid state
      would be an organic ADDE, accompanied by a functional EDE in the absence of
      meibomian gland dysfunction. This functional EDE would respond to agents that
      expand the tear volume, restore corneal sensitivity, or provide an artificial
      tear film lipid layer.

PMID- 19383278
TI  - Impression cytology: recent advances and applications in dry eye disease.
AB  - Impression cytology (IC) allows cells to be harvested from the ocular surface
      noninvasively. Superficial layers of the epithelium are removed by application of
      cellulose acetate filters or Biopore membranes, and the cells can be subsequently
      analyzed by various methods, depending on the objective of the investigation or
      pathology involved. IC techniques are easily learned, can be performed in an
      outpatient setting, and cause virtually no discomfort to the patient. IC
      facilitates the diagnosis of ocular surface disorders, including, among others,
      keratoconjunctivitis sicca, ocular surface squamous neoplasia, and ocular surface
      infections. During the past decade, IC has been used increasingly to assist in
      diagnosis of ocular surface disease, improve our understanding of the
      pathophysiology of ocular surface disease, and provide biomarkers to be used as
      outcome measures in clinical trials. Dry eye disease is one area in which IC has
      contributed to significant advances.

PMID- 19383279
TI  - Just a small, proof-of-concept study.

PMID- 19383280
TI  - Ocular surface research at the Singapore Eye Research Institute.
AB  - Established in 1997, the Singapore Eye Research Institute (SERI), which is the
      research arm of the Singapore National Eye Center (SNEC), has become one of the
      top centers for eye research in Southeast Asia. Because of research carried out
      at SERI and SNEC, Singapore now ranks as the world's top publisher of
      ophthalmology research on a per capita basis. Under the leadership of SERI
      director Donald Tan (recently succeeded by Wong Tien Yen) and scientific director
      Roger Beuerman, SERI has focused on the ocular surface, with particular emphasis
      on stem cell research, wound healing, and inflammation.

PMID- 19383283
TI  - Europe combating cancer: the European Union's commitment to cancer research in
      the 6th Framework Programme.
AB  - As one of the major health issues in Europe, cancer was a research priority in
      the 6th Framework Programme (2002-2006). About 485 million euros were devoted to
      this theme, which allowed funding of 108 multidisciplinary transnational
      projects. A significant part of them was large-scale initiatives addressing
      complex issues through a broad combination of competences. All major types of
      cancer were covered, as well as the three dimensions such as prevention,
      diagnostic and treatment, with a particular emphasis on translational research
      aiming at bringing basic knowledge on medical practice. This approach will be
      continued in the 7th Framework Programme (2007-2013), together with a
      strengthened effort to improve the coordination of European cancer research,
      which is fragmented and in which EU action represents only a small part. EU
      cancer research will also be addressed within the reinforced efforts in the areas
      of pharmaceutical and technological developments as well as common aetiological
      mechanisms of diseases that the 7th Framework Programme will undertake.

PMID- 19383284
TI  - The role of histone deacetylases (HDACs) in human cancer.
AB  - The balance of histone acetylation and deacetylation is an epigenetic layer with
      a critical role in the regulation of gene expression. Histone acetylation induced
      by histone acetyl transferases (HATs) is associated with gene transcription,
      while histone hypoacetylation induced by histone deacetylase (HDAC) activity is
      associated with gene silencing. Altered expression and mutations of genes that
      encode HDACs have been linked to tumor development since they both induce the
      aberrant transcription of key genes regulating important cellular functions such
      as cell proliferation, cell-cycle regulation and apoptosis. Thus, HDACs are among
      the most promising therapeutic targets for cancer treatment, and they have
      inspired researchers to study and develop HDAC inhibitors.

PMID- 19383285
TI  - Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis
      and prognosis.
AB  - The development of cancer is driven by the accumulation of scores of alterations
      affecting the structure and function of the genome. Equally important in this
      process are genetic alterations and epigenetic changes. Whereas the former
      disrupt normal patterns of gene expression, sometimes leading to the expression
      of abnormal, constitutively active proteins, the latter deregulate the mechanisms
      such as transcriptional control leading to the inappropriate silencing or
      activation of cancer-associated genes. Both types of changes are inheritable at
      the cellular level, thus contributing to the clonal expansion of cancer cells. In
      this review, we summarize current knowledge on how genetic alterations in
      oncogenes or tumour suppressor genes, as well as epigenetic changes, can be
      exploited in the clinics as biomarkers for cancer detection, diagnosis and
      prognosis. We propose a rationale for identifying alterations that may have a
      functional impact within a background of "passenger" alterations that may occur
      solely as the consequence of deregulated genetic and epigenetic stability. Such
      functional alterations may represent candidates for targeted therapeutic
      approaches.

PMID- 19383286
TI  - Cancer therapeutic antibodies come of age: targeting minimal residual disease.
AB  - Ten years after the first clinical application of Rituximab, an anti-CD20
      recombinant monoclonal antibody, immunotherapy has become common practice in
      oncology wards. Thanks to the great diversity of the immune system and the
      powerful methodology of genetic engineering, the pharmacologic potential of
      antibody-based therapy is far from exhaustion. The recent application of
      Trastuzumab, an antibody to a receptor tyrosine kinase, in adjuvant breast cancer
      therapy marks the beginning of a new phase in cancer treatment. Here we discuss
      molecular mechanisms of antibody-based therapy, the emerging ability to target
      minimal disease and the therapeutic potential of combining antibodies with other
      modalities.

PMID- 19383287
TI  - Functional role of Meox2 during the epithelial cytostatic response to TGF-beta.
AB  - Transforming growth factor beta (TGF-beta) suppresses epithelial cell growth. We
      have identified a new target gene of the TGF-beta/Smad pathway, Meox2, encoding
      the homeodomain transcription factor that is known to regulate endothelial cell
      proliferation and muscle development. Knockdown of endogenous Meox2 by RNA
      interference prevented the TGF-beta1-induced cytostatic response. Moreover,
      ectopic Meox2 suppressed epithelial cell proliferation in cooperation with TGF
      beta1, and mediated induction of the cell cycle inhibitor gene p21.
      Transcriptional induction of p21 by Meox2 required a distal region of the p21
      promoter that spans the p53-binding site. We show that Meox2 can form protein
      complexes with Smads leading to cooperative regulation of p21 gene expression.
      Finally, we found that in cell models that undergo both cell cycle arrest and
      epithelial-mesenchymal transition (EMT), ectopic Meox2 failed to induce EMT and
      inhibited the proper EMT response to TGF-beta. Thus, Meox2 is primarily involved
      in the TGF-beta tumor suppressor pathway.

PMID- 19383288
TI  - Mice thrive without Cdk4 and Cdk2.
AB  - Mammalian cell division is thought to be driven by sequential activation of
      several Cyclin-dependent kinases (Cdk), mainly Cdk4, Cdk6, Cdk2 and Cdk1. Since
      mice lacking Cdk4, Cdk6 or Cdk2 are viable, it has been proposed that they play
      compensatory roles. We report here that mice lacking Cdk4 and Cdk2 complete
      embryonic development to die shortly thereafter presumably due to heart failure.
      However, conditional ablation of Cdk2 in adult mice lacking Cdk4 does not result
      in obvious abnormalities. Moreover, these double mutant mice recover normally
      after partial hepatectomy. In culture, Cdk4(-/-);Cdk2(-/-) embryonic fibroblasts
      become immortal, display robust pRb phosphorylation and have normal S phase
      kinetics. These observations indicate that Cdk4 and Cdk2 are dispensable for the
      mammalian cell cycle and for adult homeostasis.

PMID- 19383289
TI  - Characterization of breast precancerous lesions and myoepithelial hyperplasia in
      sclerosing adenosis with apocrine metaplasia.
AB  - The identification as well as the molecular characterization of breast
      precancerous lesions in terms of increased risk of progression and/or recurrence
      is becoming a critical issue today as improved non-surgical procedures are
      detecting cancer at an earlier stage. The strategy we have been pursuing to
      identify early apocrine breast lesions is based on the postulate that invasive
      apocrine carcinomas evolve from epithelial cells in terminal duct lobular units
      (TDLUs) in a stepwise manner that involves apocrine metaplasia of normal breast
      epithelia, hyperplasia, atypia, and apocrine carcinoma in situ. First, we
      identify specific protein biomarkers for benign apocrine metaplasia and
      thereafter we search for biomarkers that are highly overexpressed by pure
      invasive apocrine carcinomas. Here we present studies in which we have used
      antibodies against components of a benign apocrine signature that includes 15
      prostaglandin dehydrogenase (15-PGDH), a protein that is expressed by all benign
      apocrine lesions, and markers that are highly overexpressed by pure invasive
      apocrine carcinomas such as MRP14 (S100A9), psoriasin (S100A7), and p53 to
      identify precancerous lesions in sclerosing adenosis (SA) with apocrine
      metaplasia. The latter is a benign proliferative lesion of the breast that
      exhibits an increase in the size of the TDLUs and characterized by retained two
      cell lining, and myoepithelial (ME) and stromal hyperplasia. SA with apocrine
      metaplasia, i.e. apocrine adenosis (AA), presents with a higher degree of
      atypical apocrine hyperplasia, and these lesions are believed to be precursors of
      apocrine carcinoma, in situ and invasive. Analysis of 24 selected SA samples with
      apocrine metaplasia revealed non-obligate putative apocrine precancerous lesions
      that displayed some, or in same cases all the three markers associated with pure
      invasive apocrine carcinomas. These studies also revealed p53 positive, non
      apocrine putative precancerous lesions as well as novel phenotypes for ME and
      some luminal cells characterized by the expression of cytokeratin 15.

PMID- 19383291
TI  - Identifying estrogen receptor target genes.
AB  - The estrogen receptor (ER) is a ligand inducible transcription factor that
      regulates a large number of target genes. These targets are particularly relevant
      in breast cancer, where the sensitivity of the tumor to estrogens determines
      whether the patients can be treated with endocrine therapy such as tamoxifen.
      Identifying genomic ER targets is a daunting task. Quantifying expression levels
      of suspected target genes after estradiol stimulation or, more recently, using
      expression microarrays to this effect will reveal which genes are regulated by
      estradiol, however, without discriminating between direct and indirect targets.
      The identification of the palindromic sequence that defines the estrogen
      responsive element (ERE) allows for the in silico discovery of putative ER
      targets in the genome. However the ER can also bind imperfect EREs and half
      sites, and can bind indirectly via other factors. Chromatin immunoprecipitation
      (ChIP) can yield all ER genomic target sites. Coupling of ChIP with genome-wide
      tiling arrays allows for the genome-wide unbiased identification of direct ER
      target sequences.

PMID- 19383292
TI  - Presence of bone marrow micrometastasis is associated with different recurrence
      risk within molecular subtypes of breast cancer.
AB  - Expression profiles of primary breast tumors were investigated in relation to
      disseminated tumor cells (DTCs) in bone marrow (BM) in order to increase our
      understanding of the dissemination process. Tumors were classified into five pre
      defined molecular subtypes, and presence of DTC identified (at median 85 months
      follow-up) a subgroup of luminal A patients with particular poor outcome
      (p=0.008). This was not apparent for other tumor subtypes. Gene expression
      profiles associated with DTC and with systemic relapse for luminal A patients
      were identified. This study suggests that DTC in BM differentially distinguishes
      clinical outcome in patients with luminal A type tumors and that DTC-associated
      gene expression analysis may identify genes of potential importance in tumor
      dissemination.

PMID- 19383293
TI  - Gene expression profiling of human lymph node metastases and matched primary
      breast carcinomas: clinical implications.
AB  - The genetic program that drives tumor metastasis and the mode and timing of its
      initiation are of great practical significance to clinical management. Modern
      technical advances open new opportunities for gaining useful relevant
      information. Gene expression profiles of histologically-verified viable tissue
      from lymph node metastases were compared with those of matched primary breast
      cancers from 10 different patients, among samples from over 400 cases, using high
      throughput oligonucleotide arrays comprising probes for 22,000 genes. It was
      observed that metastases have very similar expression signatures to their parent
      tumors. However, detailed computational analysis revealed that a small number of
      genes were consistently differentially expressed between 100% of tumors and
      metastases, suggesting that these are mechanistically important. Lists of such
      candidate genes, of potential clinical interest, are provided. We interpret these
      results in the framework of a meta-analysis of previous investigations by others
      and ourselves and of existing clinical knowledge on the behavior of human tumors.
      The collective data show that metastases resemble their primary tumors but the
      signatures obtained in different studies are not sufficiently reproducible or
      informative to be prognostically useful, although they do give valuable insights
      into the pathogenesis and biology of human tumor metastasis. The findings
      indicate that the genetic program encoding metastasis is implemented
      progressively over time although, occasionally, this evolution can occur rapidly,
      early in the life of the neoplasm. The important clinical significance of this
      deduction is that, in most patients, early detection provides time for
      appropriate therapeutic intervention to be effective in obstructing metastasis.

PMID- 19383294
TI  - Phosphoprotein Keratin 23 accumulates in MSS but not MSI colon cancers in vivo
      and impacts viability and proliferation in vitro.
AB  - Transcript profiling of 27 normal colon mucosas and 258 adenocarcinomas showed
      Keratin23 to be increased in 78% microsatellite-stable tumors, while
      microsatellite-instable tumors showed low transcript levels, comparable to normal
      mucosas. Immunohistochemical analyses demonstrated that 88% of microsatellite
      instable tumors were negative for Keratin23 protein, while 70% of MSS tumors and
      metastases derived from MSS-tumors showed high Keratin23 levels.
      Immunofluorescence analysis localized Keratin23 in the Golgi-apparatus. Golgi
      accumulation was unique for gastrointestinal adenocarcinomas. Immunoprecipitation
      and 2D-blot analysis revealed Keratin23 to be a 46.8 kDa phosphoprotein.
      Keratin23 impaired the proliferation of human colon cancer cells significantly,
      leading to cell death in microsatellite-instable but not microsatellite-stable
      cell lines, while COS7 cells experienced multiple nuclei and apoptosis. Keratin23
      expression correlated significantly with transcription factor CEBPB. In
      conclusion, Keratin23 expression is a novel and important difference between
      microsatellite-stable and microsatellite-instable colon cancers.

PMID- 19383296
TI  - Examination of gap junctional, intercellular communication by in situ
      electroporation on two co-planar indium-tin oxide electrodes.
AB  - Gap junctions are plasma membrane channels between neighboring cells. We
      previously described a powerful technique where gap junctional, intercellular
      communication (GJIC) of adherent cells can be examined by in situ electroporation
      on a slide, part of which is coated with electrically conductive and transparent
      indium-tin oxide. An electric pulse is applied through an electrode placed on the
      cells in the presence of the tracking dye, Lucifer yellow (LY). The pulse causes
      LY's penetration into the cells growing on the conductive part of the slide, and
      the subsequent migration of the dye to the non-electroporated cells growing on
      the non-conductive area is microscopically observed under fluorescence
      illumination. Although this technique is adequate for a number of cell lines, the
      turbulence generated as the electrode is removed can cause cell detachment, which
      makes GJIC examination problematic. In this communication, we describe a slide
      configuration where junctional communication can be examined in the absence of an
      upper electrode: Cells are grown on two co-planar electrodes separated by a
      barrier which diverts the electric field, rendering it vertical to the cell
      layer. The elimination of an upper electrode is especially valuable for the
      electroporation of sensitive cells, such as terminally differentiated adipocytes.
      This technique can also be used for the introduction of other non-permeant
      molecules such as peptides or siRNA, followed by examination of the cellular
      phenotype or gene expression levels in situ.

PMID- 19383295
TI  - Identification of alternatively spliced TIMP-1 mRNA in cancer cell lines and
      colon cancer tissue.
AB  - TIMP-1 is a promising new candidate as a prognostic marker in colorectal and
      breast cancer. We now describe the discovery of two alternatively spliced
      variants of TIMP-1 mRNA. The two variants lacking exon 2 (del-2) and 5 (del-5),
      respectively, were identified in human cancer cell lines by RT-PCR. The del-2
      variant was, furthermore, detected in extracts from 12 colorectal cancer tissue
      samples. By western blotting additional bands of lower molecular mass than full
      length TIMP-1 were identified in tumor tissue, but not in plasma samples obtained
      from cancer patients. The two splice variants of TIMP-1 may hold important
      clinical information, and either alone or in combination with measurement of full
      length TIMP-1 they may improve the prognostic and/or predictive value of TIMP-1
      analyses.

PMID- 19383298
TI  - Barriers to translation of research.

PMID- 19383299
TI  - The MINDACT trial: the first prospective clinical validation of a genomic tool.
AB  - One of the main challenges in oncology today has become to distinguish accurately
      between those patients who need adjuvant treatment and those who do not. This,
      together with the identification of the best type of therapy for the individual
      patient and the development of drugs targeting specific characteristics of tumour
      cells, are the goals of treatment tailoring or personalized medicine. The MINDACT
      trial (Microarray In Node negative Disease may Avoid ChemoTherapy) was recently
      launched with the aim of prospectively validating the superior performance of a
      new prognostic RNA-based tool--the Amsterdam 70-gene profiler MammaPrint, in
      order to implement its use in clinical practice later on. This manuscript shortly
      reviews the rational, design and logistics of MINDACT.

PMID- 19383300
TI  - Is metastasis predetermined?

PMID- 19383302
TI  - Prognostic value of peripheral blood double detection of CK19 and MUC1 mRNA
      positive cells detected by RT-quantitative PCR in 94 breast cancer patients with
      a follow up of 9 years.

PMID- 19383304
TI  - A consolidated catalogue and graphical annotation of dbSNP polymorphisms in the
      human tissue kallikrein (KLK) locus.
AB  - The human tissue kallikreins, 15 secreted serine proteases, may play diverse
      roles in pathophysiology. The National Center for Biotechnology Information's
      dbSNP was mined for polymorphisms located within the kallikrein (KLK) locus using
      custom-designed "ParSNPs" and "LocusAnnotator" software tools. Using "ParSNPs", a
      filterable catalogue of 1856 KLK polymorphisms (1023 validated) was generated.
      "LocusAnnotator" was used to annotate the KLK locus sequence with gene and
      polymorphism features. A second locus was examined to validate the use of both
      programs on a non-kallikrein locus. This report may assist in the informed
      selection of KLK polymorphisms for future association and biochemical studies in
      relation to disease. Furthermore, "ParSNPs" and "LocusAnnotator" are available at
      no cost from our website (www.acdcLab.org/annotations) to examine other loci.

PMID- 19383305
TI  - Use of high density antibody arrays to validate and discover cancer serum
      biomarkers.
AB  - Perhaps the greatest barrier to translation of serum biomarker discoveries is the
      inability to evaluate putative biomarkers in high throughput validation studies.
      Here we report on the development, production, and implementation of a high
      density antibody microarray used to evaluate large numbers of candidate ovarian
      cancer serum biomarkers. The platform was shown to be useful for evaluation of
      individual antibodies for comparative analysis, such as with disease
      classification, and biomarker validation and discovery. We demonstrate its
      performance by showing that known tumor markers behave as expected. We also
      identify several promising biomarkers from a candidate list and generate
      hypotheses to support new discovery studies.

PMID- 19383303
TI  - New insights into the functional mechanisms and clinical applications of the
      kallikrein-related peptidase family.
AB  - The Kallikrein-related peptidase (KLK) family consists of fifteen conserved
      serine proteases that form the largest contiguous cluster of proteases in the
      human genome. While primarily recognized for their clinical utilities as
      potential disease biomarkers, new compelling evidence suggests that this family
      plays a significant role in various physiological processes, including skin
      desquamation, semen liquefaction, neural plasticity, and body fluid homeostasis.
      KLK activation is believed to be mediated through highly organized proteolytic
      cascades, regulated through a series of feedback loops, inhibitors, auto
      degradation and internal cleavages. Gene expression is mainly hormone-dependent,
      even though transcriptional epigenetic regulation has also been reported. These
      regulatory mechanisms are integrated with various signaling pathways to mediate
      multiple functions. Dysregulation of these pathways has been implicated in a
      large number of neoplastic and non-neoplastic pathological conditions. This
      review highlights our current knowledge of structural/phylogenetic features,
      functional role and regulatory/signaling mechanisms of this important family of
      enzymes.

PMID- 19383309
TI  - Cancer research in the UK: A policy review of the junior academic clinical
      faculty.
AB  - Despite huge sums spent on academic clinical raining worldwide there is
      surprisingly little research to inform policymakers. This study addresses the
      junior faculty in the UK's cancer research community through both current Fellows
      and senior clinicians and policymakers. Funding organisations under the National
      Cancer Research Institute umbrella currently support 176 junior faculty fellows
      (studying towards MD [2 year postgraduate research degree] or PhD) with the
      majority in medical oncology (49%). Craft specialities (surgery and pathology)
      had a very modest presence in the junior faculty. The cancer research specific
      junior faculty makes up a major component of all available junior faculty from
      National Cancer Research Institute (NCRI) partners (ca. 31%) and is supported
      both by direct funding to Fellows and via junior faculty positions on clinical
      programme grants. There was almost universal support for the value of the
      research experience despite only two thirds of the current cohort expressing a
      desire to continue to the next level (Clinician Scientist grade). Major issues
      identified were mentorship, supervision time, pay parity and fit with new UK
      Clinical Research Collaboration / Modernising Medical Careers (UKCRC/MMC)
      clinician training programme.

PMID- 19383306
TI  - Identification of a subset of breast carcinomas characterized by expression of
      cytokeratin 15: relationship between CK15+ progenitor/amplified cells and pre
      malignant lesions and invasive disease.
AB  - Recently, we presented evidence--based on the analysis of benign
      hyperproliferative lesions of the breast--for the presence of cells that express
      the stem cell marker cytokeratin (CK) 15 in combination with CK19, a protein
      widely expressed by mammary epithelial cells. Here we report the finding of a
      subset of breast carcinomas characterized by expression of CK15. CK15 expressing
      tumors constituted 5% (6 out of 120; 4 of ductal type and 2 of lobular type) of
      the high-risk breast carcinomas examined by gel-based proteomics and
      immunohistochemistry. Five out of the six CK15+ carcinomas were CK15+/CK19-. The
      remaining tumor was mainly composed of cells expressing both CK15 and CK19
      (CK15+/CK19+), but it also contained invasive areas with cells expressing only
      one of these makers (CK15+/CK19- and CK15-/CK19+ cells). To address the
      relationship between putative luminal progenitor/amplified CK15+ cells and
      malignant disease, and to determine whether cells/lesions lose expression of CK15
      as a result of tumour initiation and/or progression, we searched among our sample
      set for carcinomas in which invasive tumor areas co-existed with non-malignant
      cells and hyperproliferative and known pre-malignant lesions. Only one such
      tumour was found (T71), a CK15-/CK19+/p53+ carcinoma that contained p53 negative
      non-malignant epithelial cells exhibiting a variety of, CK15/CK19 cellular
      phenotypes (CK15+/CK19+; CK15+/CK19-; CK15-/CK19+; CK15-/CK19-), often associated
      with simple columnar cells. Single layers of epithelial cells exhibiting all four
      CK15/CK19 phenotypes were observed contiguous to areas of atypical ductal
      hyperplasia that contained p53 positive cells that lost CK15 expression (CK15
      /CK19+) and had a very similar phenotype to those of the neighboring ductal
      carcinoma in situ (DCIS) and invasive cells. The undifferentiated CK15+/CK19+
      cells, which had the phenotype CK15+/CK19+/CK14+/CK8+ and -/ER-/PgR-/AR-/CD44+
      (weak)/CK17-/p63-/vimentin+/Ki67-/Bcl-2+ (weak)/GATA-3-/p53-, most likely
      correspond to lineage-restricted luminal progenitor cells able to generate the
      other more differentiated CK15/CK19 cellular phenotypes, thus giving rise to the
      daunting intratumour heterogeneity displayed by carcinoma T71. Cells with a very
      similar phenotype to the CK15+/CK19+ progenitor cells were observed in a juvenile
      fibroadenoma as well as in the large collecting ducts of the breast. The latter,
      however, expressed in addition CK14 and had a phenotype (CK15+/CK19+/CK14+/CK8+
      (weak)/ER-/PgR-/AR-/CD44+ (weak)/CK17-/p63-/vimentin-/Ki67-/Bcl-2+/GATA-3-/p53-)
      that resembled that of the putative normal adult breast stem cells as inferred
      from published data. Further molecular characterization of these progenitor cells
      as well as unraveling of the signaling pathways that regulate their growth and
      differentiation may prove invaluable for developing novel therapeutic strategies
      that target cancer at an early stage.

PMID- 19383310
TI  - News from the 2007 San Antonio Breast Cancer Symposium.

PMID- 19383307
TI  - Human papillomavirus is a favourable prognostic factor in tonsillar cancer and
      its oncogenic role is supported by the expression of E6 and E7.
AB  - From 1970 to 2002 in the Stockholm area, we revealed a parallel three-fold
      increase in the incidence of tonsillar cancer and the proportion of human
      papillomavirus (HPV) positive tonsillar cancer cases, indicating a possible role
      of HPV infection in this disease. We have now examined whether HPV and viral load
      in pre-treatment tonsillar cancer biopsies correlates to disease prognosis, and
      whether the presence of HPV-16 E6 and E7 mRNA could be ascertained. The presence
      of HPV-16, but not viral load, in tonsillar cancer was shown to be a favourable
      prognostic factor for clinical outcome. Moreover, E6 and/or E7 were expressed in
      almost all assessable HPV-16 positive cases, supporting an oncogenic role of HPV
      16 in tonsillar cancer.

PMID- 19383311
TI  - 49th annual meeting of American Society of Hematology (Atlanta, Georgia, 8-11
      December).

PMID- 19383312
TI  - High throughput molecular diagnostics in bladder cancer - on the brink of
      clinical utility.
AB  - An enormous body of high-throughput genome-wide data, in particular gene
      expression data, has been gathered from roughly all human cancer forms in the
      past 10 years. This has widely increased our understanding of the cancer disease
      and its molecular changes and pathways, with a large contribution from studies of
      cancer cell lines and functional genomics. In the last three years, the focus has
      been moved to clinical outcome parameters as recurrence, progression, metastasis
      and treatment response. The huge variability of molecular changes and poor
      availability of samples have hampered progress in the field of epithelial cancer
      (carcinoma). However, independent validation of molecular profiles across high
      throughput platforms, methods, laboratories and cancer populations has recently
      been successfully performed for several carcinomas, including bladder cancer.
      Application of advanced bioinformatics to identify interrelated pathways has
      revealed common signatures predictive of molecular subgroups, improving
      histopathological diagnosis, and ultimately outcome prediction. With breast
      cancer leading the field, colorectal, bladder and renal cell carcinomas well on
      their way, and many others soon to join, the era of clinical applications of high
      throughput molecular methods in cancer lies closely ahead. This review
      illustrates in detail the perspectives for the management of bladder cancer.

PMID- 19383314
TI  - Prognostic factors versus predictive factors: Examples from a clinical trial of
      erlotinib.
AB  - It would be helpful to have factors that could identify patients who will, or
      will not, benefit from treatment with specific therapies. Ideally, these should
      be molecular-based factors. When results with molecular-based factors are
      disappointing, physicians often use clinical characteristics to make treatment
      decisions. Several characteristics have been suggested to predict sensitivity to
      epidermal growth factor receptor inhibitors in patients with non-small lung
      cancer, including gender, histology, smoking history. This report demonstrates
      that gender and histology are actually prognostic, rather than predictive
      factors. Before biomarkers or clinical characteristics are included in guidelines
      for selecting patients for specific treatments, it is imperative that the
      prognostic effects of these factors are distinguished from their ability to
      predict a differential clinical benefit from the specific treatment.

PMID- 19383313
TI  - Human cutaneous melanoma; a review of NRAS and BRAF mutation frequencies in
      relation to histogenetic subclass and body site.
AB  - A majority of cutaneous melanomas show activating mutations in the NRAS or BRAF
      proto-oncogenes, components of the Ras-Raf-Mek-Erk signal transduction pathway.
      Consistent data demonstrate the early appearance, in a mutually exclusive manner,
      of these mutations. The purpose of this paper is to summarize the literature on
      NRAS and BRAF activating mutations in melanoma tumors with respect to available
      data on histogenetic classification as well as body site and presumed UV
      exposure. Common alterations of the signal transducing network seem to represent
      molecular hallmarks of cutaneous melanomas and therefore should continue to
      strongly stimulate design and testing of targeted molecular interventions.

PMID- 19383315
TI  - Androgens act synergistically to enhance estrogen-induced upregulation of human
      tissue kallikreins 10, 11, and 14 in breast cancer cells via a membrane bound
      androgen receptor.
AB  - The regulation of gene expression by steroid hormones plays an important role in
      the normal development and function of many organs, as well as in the
      pathogenesis of endocrine-related cancers, especially breast cancer. However,
      clinical data suggest that combined testosterone and estrogen treatments on post
      menopausal women increase the risk of breast cancer. Experiments have shown that
      many, if not all kallikreins are under steroid hormone regulation in breast
      cancer cell lines. Their implication as prognostic and diagnostic markers has
      also been well-documented. Thus, we investigated the effect of combined hormone
      stimulation with androgens and 17beta-estradiol on the ductal caricinoma cell
      line BT474. This cell line has been shown to be sensitive to both, androgens
      (secreting PSA) and estrogens (secreting a number of kallikreins including KLK10,
      11, and KLK14). We found that PSA expression was downregulated upon combined
      hormone stimulation, confirming reports that estrogen can antagonize and block
      the activity of the androgen receptor. Upon analysis of estrogen-sensitive
      kallikreins 10, 11, and 14, all showed to be synergistically enhanced in their
      expression three- to fourfold, upon joint hormone treatment versus individual
      hormone stimulation. The enhancement is dependent upon the action of androgens as
      treatment with the androgen receptor antagonist cyproterone actetate normalized
      the expression of KLK10, 11, and KLK14 to estrogen-stimulation levels. The
      synergistic effects between estrogens and androgens on estrogen-sensitive genes
      may have implications on the role of the kallikreins in associated risk of breast
      cancer and progression.

PMID- 19383316
TI  - Gene expression signature associated with BRAF mutations in human primary
      cutaneous melanomas.
AB  - With the aim to correlate BRAF mutation status with gene expression in human
      primary cutaneous melanomas, and thus to get more insight on the consequences of
      BRAF mutation on cell biology, we analyzed all expression data obtained in
      melanomas from which DNA was extracted from the same tissue slides that were used
      for the expression study. A cohort of 69 frozen primary melanoma whose
      oligonucleotide micro-array expression data were available, were genotyped for
      BRAF and NRAS genes. The expression data from these melanomas were re-analyzed
      according to BRAF mutational status. A set of 250 probes representing 209 genes
      that were significantly (raw P< or =0.001) associated with BRAF mutation status
      was identified and 17 of these were previously shown to be implicated in
      cutaneous melanoma progression or pigmentation pathway-associated genes driven by
      the microphthalmia transcription factor (MITF). The list of 34 top probes
      contained no more than 1% of false discoveries with a probability of 0.95. Among
      the genes that differentiated most strongly between BRAF mutated and non-mutated
      melanomas, there were those involved in melanoma immune response such as MAGE-D2,
      CD63, and HSP70. These findings support the immunogenicity of BRAF(V600E),
      eliciting patients T-cell responses in various in vitro assays. The genes whose
      expression is associated with BRAF mutations are not simply restricted to the
      MAPK/ERK signaling but also converge to enhanced immune responsiveness, cell
      motility and melanosomes processing involved in the adaptative UV response.

PMID- 19383321
TI  - American Society of Clinical Oncology's 2008 Gastrointestinal Cancers Symposium
      (ASCO GI), January 25-27, 2008, Orlando, Florida.

PMID- 19383317
TI  - The apoptosis linked gene ALG-2 is dysregulated in tumors of various origin and
      contributes to cancer cell viability.
AB  - The apoptosis linked gene-2 (ALG-2), discovered as a proapoptotic calcium binding
      protein, has recently been found upregulated in lung cancer tissue indicating
      that this protein may play a role in the pathology of cancer cells and/or may be
      a tumor marker. Using immunohistochemistry on tissue microarrays we analysed the
      expression of ALG-2 in 7371 tumor tissue samples of various origin as well as in
      749 normal tissue samples. Most notably, ALG-2 was upregulated in mesenchymal
      tumors. No correlation was found between ALG-2 staining intensity and survival of
      patients with lung, breast or colon cancer. siRNA mediated ALG-2 downregulation
      led to a significant reduction in viability of HeLa cells indicating that ALG-2
      may contribute to tumor development and expansion.

PMID- 19383322
TI  - The Stockholm declaration signals a cultural change in Europe's approach to
      cancer research. An interview with Ulrik Ringborg.

PMID- 19383323
TI  - The Stockholm declaration.

PMID- 19383324
TI  - SNPs associated with molecular subtypes of breast cancer: on the usefulness of
      stratified Genome-wide Association Studies (GWAS) in the identification of novel
      susceptibility loci.

PMID- 19383325
TI  - NESH protein expression switches to the adverse effect of imatinib mesylate.

PMID- 19383326
TI  - Trends in the global funding and activity of cancer research.
AB  - Cancer research has carved an astonishing trajectory giving rise to a multi
      billion euro global network covering most domains of science and including all
      manner of research funders from industry to government and philanthropic funders.
      We have estimated that in 2004/2005 the global spend on cancer research was
      14,030 million euro, with the USA, dominated by the NCI (c. 83%) accounting for
      the largest absolute spend. This is between 2 and 3 times the level of per capita
      spend compared to EU-15 and Europe, respectively. In Europe, the UK is at
      comparable levels of spend compared to the USA. Funding for cancer research in
      Europe is split almost 50:50 between philanthropic and governmental sources.
      Cancer research productivity in terms of outputs (publications) is slightly
      greater in Europe compared to the USA with an increasing trend towards more
      applied (clinical) outputs. Both the USA and Europe have equally strong industry
      supported output levels.

PMID- 19383327
TI  - Epigenetics and cancer, 2nd IARC meeting, Lyon, France, 6 and 7 December 2007.
AB  - It is becoming widely accepted that epigenetic alterations are universally
      present in human malignancies and that cancer is as much a disease of abnormal
      epigenetics as it is a genetic disease. The potential utility of epigenetics and
      epigenomics in cancer research and cancer control is highlighted by the fact that
      many funding agencies put cancer epigenetics on the priority list. The goal of
      this meeting, held at the offices of the International Agency for Research on
      Cancer in Lyon, France, 6 and 7 December 2007, was to discuss recent conceptual
      and technological advances in cancer epigenetics and epigenomics, the future
      research needs in the field, and their implications for early detection, risk
      assessment and prevention of cancer. While epigenetics has been historically
      linked to phenomena that do not follow normal genetic principles of heritability,
      recent mechanistic advances have begun to change our understanding of complex
      diseases including cancer, traditionally viewed as genetic in origin. It is now
      known that epigenetic mechanisms play critical roles in regulation of many
      cellular functions and their deregulation may disrupt the control of fundamental
      processes leading to tumour formation. A flurry of screening and functional
      studies revealed that most key processes found in cancer cells, such as silencing
      of tumour suppressor genes, activation of oncogenes, aberrant cell cycle
      processes, defects in DNA repair, and deregulation of cell death, can be
      triggered by epigenetic deregulation. Two important features that distinguish
      epigenetic changes from genetic alterations are the gradual appearance and
      reversibility of epigenetic events. These features make epigenetic alterations an
      attractive target for therapeutic intervention and the development of preventive
      strategies. For example, aberrant patterns of DNA methylation and histone
      acetylation and methylation can be targeted by drugs aiming to re-activate
      epigenetically silenced genes. Until now, most studies on epigenetic changes in
      cancer were generally focused on specific genes. However, this meeting also
      stressed the need to take advantage of recent progress in epigenomics and
      emergence of powerful technologies for detection of epigenetic changes in high
      throughput and genome-wide settings. This may further advance our capacity to
      evaluate the contribution of epigenetic changes induced by environmental
      epimutagens to human cancer. This information may prove critical for the design
      of efficient strategies for early diagnosis, therapy, and prevention of cancer.

PMID- 19383328
TI  - Molecular aspects of tumour hypoxia.
AB  - Hypoxia is an important feature of the microenvironment of a wide range of solid
      tumours. Its critical role in radio- and chemoresistance and its significance as
      an adverse prognostic factor have been well established over the last decades. On
      a cellular level, hypoxia evokes a complex molecular response with a central role
      for the HIF-1 pathway. The cellular processes under control of HIF-1 contain
      important prognostic information and comprise potential candidates for directing
      hypoxia-modifying therapies. This review will provide an overview of the current
      knowledge on the molecular aspects of tumour hypoxia and the link to clinical
      practice.

PMID- 19383329
TI  - Mutant p53 targeting by the low molecular weight compound STIMA-1.
AB  - Reactivation of mutant p53 in human tumor cells should induce cell death by
      apoptosis and thus eliminate the tumor. Several small molecules that reactivate
      mutant p53 have been identified. Here we show that STIMA-1, a low molecular
      weight compound with some structural similarities to the previously identified
      molecule CP-31398, can stimulate mutant p53 DNA binding in vitro and induce
      expression of p53 target proteins and trigger apoptosis in mutant p53-expressing
      human tumor cells. Human diploid fibroblasts are significantly more resistant to
      STIMA-1 than mutant or wild type p53-carrying tumor cells. STIMA-1 may provide
      new insights into possible mechanisms of mutant p53 reactivation and thus
      facilitate the development of novel anticancer drugs that target mutant p53
      carrying tumors.

PMID- 19383330
TI  - Pharmacologically enhanced expression of GPNMB increases the sensitivity of
      melanoma cells to the CR011-vcMMAE antibody-drug conjugate.
AB  - GPNMB is a melanoma-associated glycoprotein that is targeted by the CR011-vcMMAE
      antibody-drug conjugate (ADC). Previous studies have shown that CR011-vcMMAE
      induces the apoptosis of GPNMB-expressing tumor cells in vitro and tumor
      regression in xenograft models. This ADC is currently in clinical trials for
      melanoma. In the present investigation, a variety of compounds were examined for
      their ability to increase the expression of GPNMB by cancer cells. These
      experiments lead to the identification of three distinct groups of compounds that
      increased GPNMB, some of which were shown to enhance the sensitivity of melanoma
      cells to CR011-vcMMAE. These data indicate that it may be possible to increase
      the anticancer activity of CR011-vcMMAE through pharmacological enhancement of
      GPNMB expression for potential therapeutic benefit.

PMID- 19383331
TI  - 3-Bromopyruvate as inhibitor of tumour cell energy metabolism and
      chemopotentiator of platinum drugs.
AB  - Tumour cells depend on aerobic glycolysis for adenosine triphosphate (ATP)
      production, making energy metabolism an interesting therapeutic target. 3
      Bromopyruvate (BP) has been shown by others to inhibit hexokinase and eradicate
      mouse hepatocarcinomas. We report that similar to the glycolysis inhibitor 2
      deoxyglucose (DG), BP rapidly decreased cellular ATP within hours, but unlike DG,
      BP concomitantly induced mitochondrial depolarization without affecting levels of
      reducing equivalents. Over 24h, and at equitoxic doses, DG reduced glucose
      consumption more than did BP. The observed BP-induced loss of ATP is therefore
      largely due to mitochondrial effects. Cell death induced over 24h by BP, but not
      DG, was blocked by N-acetylcysteine, indicating involvement of reactive oxygen
      species. BP-induced cytotoxicity was independent of p53. When combined with
      cisplatin or oxaliplatin, BP led to massive cell death. The anti-proliferative
      effects of low-dose platinum were strikingly potentiated also in resistant p53
      deficient cells. Together with the reported lack of toxicity, this indicates the
      potential of BP as a clinical chemopotentiating agent.

PMID- 19383332
TI  - Prognostic value of Bcl-2 in breast cancer patients treated with neoadjuvant
      anthracycline based chemotherapy.
AB  - We have analyzed the predictive/prognostic value of Bcl-2 protein in breast
      cancer patients treated with neoadjuvant chemotherapy. One hundred and ten
      patients were submitted to two different chemotherapeutic regimens: a) 5
      fluorouracil, adriamycin or epirubicin, and cyclophosphamide (FAC/FEC) during 2-6
      cycles before surgery and 3 or 4 additional cycles of FAC/FEC after surgery
      (n=40) and b) doxorubicin (D) 75 mg/m(2) or epirubicin (E) 120 mg/m(2) during 4
      cycles before surgery, and 6 cycles of cyclophosphamide, methotrexate, and 5
      fluorouracil (CMF) after surgery (n=70). Bcl-2 expression, evaluated by
      immunohistochemistry, did not change significantly after chemotherapy and was not
      related to clinical/pathological response. In FAC/FEC group, Bcl-2 positive
      expression after chemotherapy correlated with better disease free survival (DFS)
      and overall survival (OS) (P=0.008 and P=0.001). In D/E group, Bcl-2 also
      correlated with better DFS and OS (P=0.03 and P=0.054) in the post-chemotherapy
      biopsies. An unusual nuclear localization of Bax was observed in some biopsies,
      but this localization did not correlate with the tumor response or outcome of the
      patients. We found that a high Bcl-2 expression had no predictive value but had
      prognostic value in breast cancer patients treated with neoadjuvant anthracycline
      based chemotherapy.

PMID- 19383334
TI  - Innovations, challenges and future prospects of oncoproteomics.
AB  - Oncoproteomics is playing an increasingly important role in the diagnosis and
      management of cancer as well as in the development of personalized treatment of
      cancer. Innovative proteomic technologies relevant to cancer are described
      briefly, which are helping in the understanding of mechanism of drug resistance
      in cancer and will provide some leads to improve the management. Most important
      of these are nanoproteomics, i.e. application of nanobiotechnology to proteomics
      is playing an important role in nanooncology. Examples of some cancers will be
      given to point out the challenges and future prospects of oncoproteomics
      including those involving translation of technologies from the bench to the
      bedside.

PMID- 19383335
TI  - Unlucky number 13? Differential effects of KIT exon 13 mutation in
      gastrointestinal stromal tumors.

PMID- 19383337
TI  - E2-mediated cathepsin D (CTSD) activation involves looping of distal enhancer
      elements.
AB  - Estrogen receptor alpha (ERalpha) is a ligand dependent transcription factor that
      regulates the expression of target genes through interacting with cis-acting
      estrogen response elements (EREs). However, only a minority of ERalpha binding
      sites are located within the proximal promoter regions of responsive genes. Here
      we report the characterization of an ERE located 9kbp upstream of the TSS of the
      cathepsin D gene (CTSD) that up-regulates CTSD expression upon estrogen
      stimulation in MCF-7 cells. Using ChIP, we show recruitment of ERalpha and
      phosphorylated PolII at the CTSD distal enhancer region. Moreover, we determine
      the kinetics of transient CpG methylation on the promoter region of CTSD and for
      the first time, at a distal enhancer element. We show that ERalpha is crucial for
      long-distance regulation of CTSD expression involving a looping mechanism.

PMID- 19383338
TI  - Inside the European science foundation.

PMID- 19383339
TI  - Patient organisations aim for greater collaboration.

PMID- 19383336
TI  - Overexpression of SnoN/SkiL, amplified at the 3q26.2 locus, in ovarian cancers: a
      role in ovarian pathogenesis.
AB  - High-resolution array comparative genomic hybridization of 235 serous epithelial
      ovarian cancers demonstrated a regional increase at 3q26.2 encompassing
      SnoN/SkiL, a coregulator of SMAD/TGFbeta signaling. SnoN RNA transcripts were
      elevated in approximately 80% of advanced stage serous epithelial ovarian
      cancers. In both immortalized normal (TIOSE) and ovarian carcinoma cell lines
      (OVCA), SnoN RNA levels were increased by TGFbeta stimulation and altered by
      LY294002 and JNK II inhibitor treatment suggesting that the PI3K and JNK
      signaling pathways may regulate TGFbeta-induced increases in SnoN RNA. In TIOSE,
      SnoN protein levels were reduced 15min post TGFbeta-stimulation, likely by
      proteosome-mediated degradation. In contrast, in OVCA, SnoN levels were elevated
      3h post-stimulation potentially as a result of inhibition of the proteosome. To
      elucidate the role of SnoN in ovarian tumorigenesis, we explored the effects of
      both increasing and decreasing SnoN levels. In both TIOSE and OVCA, SnoN siRNA
      decreased cell growth between 20 and 50% concurrent with increased p21 levels. In
      TIOSE, transient expression of SnoN repressed TGFbeta induction of PAI-1
      promoters with little effect on the p21 promoter or resultant cell growth. In
      contrast to the effects of transient expression, stable expression of SnoN in
      TIOSE led to growth arrest through induction of senescence. Collectively, these
      results implicate SnoN levels in multiple roles during ovarian carcinogenesis:
      promoting cellular proliferation in ovarian cancer cells and as a positive
      mediator of cell cycle arrest and senescence in non-transformed ovarian
      epithelial cells.

PMID- 19383340
TI  - Will the innovative medicines initiative really deliver innovative medicines?

PMID- 19383333
TI  - Imaging and cancer: a review.
AB  - Multiple biomedical imaging techniques are used in all phases of cancer
      management. Imaging forms an essential part of cancer clinical protocols and is
      able to furnish morphological, structural, metabolic and functional information.
      Integration with other diagnostic tools such as in vitro tissue and fluids
      analysis assists in clinical decision-making. Hybrid imaging techniques are able
      to supply complementary information for improved staging and therapy planning.
      Image guided and targeted minimally invasive therapy has the promise to improve
      outcome and reduce collateral effects. Early detection of cancer through
      screening based on imaging is probably the major contributor to a reduction in
      mortality for certain cancers. Targeted imaging of receptors, gene therapy
      expression and cancer stem cells are research activities that will translate into
      clinical use in the next decade. Technological developments will increase imaging
      speed to match that of physiological processes. Targeted imaging and therapeutic
      agents will be developed in tandem through close collaboration between academia
      and biotechnology, information technology and pharmaceutical industries.

PMID- 19383341
TI  - The state of academic cancer surgery in the UK.
AB  - Despite media and public perception to the contrary cancer surgery is the most
      important modality for the control and cure of cancer. However, after years of
      underinvestment by research funders and increasing service delivery demands the
      academic cancer surgeon is an endangered species. In an effort to improve
      evidence-based policymaking in this critical domain of cancer research the ECRM
      has conducted a semi-quantitative assessment of the state of academic cancer
      surgery in the UK. We have found that the percentage of investment in cancer
      surgical technologies R&D is less than 1% and even when this is extended to other
      diseases then this figure is still less than 1%. A decline in the overall numbers
      of academic surgical staff is paralleled by our finding that over 50% of the
      academic cancer surgeons in this survey had insufficient time for research. With
      clinical trials and surgical technology development identified as key research
      domains the majority (60-80%) did not perceive any benefit for surgical research
      in these areas as a result of the creation of the UK National Cancer Research
      Institute. We also found high support for academic surgery from colleagues but
      medium-low support from many institutions. Key policy conclusions are: (1)
      greater hypothecated investment by research funders, particularly for the
      development of surgical technologies as well as clinical trials, and (2) the
      creation of cancer surgery centres of excellence which have sufficient staffing
      and institutional support to engendered a creative academic environment.

PMID- 19383342
TI  - Biobanking for better healthcare.
AB  - Translational cancer research is highly dependent of large series of cases
      including high quality samples and their associated data. Comprehensive Cancer
      Centers should be involved in networks to enable large-scale multi-center
      research projects between the centers [Ringborg, U., de Valeriola, D., van
      Harten, W., Llombart-Bosch, A., Lombardo, C., Nilsson, K., Philip, T., Pierotti,
      M.A., Riegman, P., Saghatchian, M., Storme, G., Tursz, T., Verellen, D, 2008.
      Improvement of European translational cancer research. Collaboration between
      comprehensive cancer centers. Tumori 94, 143-146.]. Combating cancer knows many
      frontiers. Research is needed for prevention as well as better care for those who
      have acquired the disease. This implies that human samples for cancer research
      need to be sourced from distinct forms of biobanking. An easier access to these
      samples for the scientific community is considered as the main bottleneck for
      research for health, and biobanks are the most adequate site to try to resolve
      this issue [Ozols, R.F., Herbst, R.S., Colson, Y.L., Gralow, J., Bonner, J.,
      Curran Jr., W.J., Eisenberg, B.L., Ganz, P.A., Kramer, B.S., Kris, M.G., Markman,
      M., Mayer, R.J., Raghavan, D., Reaman, G.H., Sawaya, R., Schilsky, R.L.,
      Schuchter, L.M., Sweetenham, J.W., Vahdat, L.T., Winn, R.J., and the American
      Society of Clinical Oncology, 2007. Clinical cancer advances 2006: major research
      advances in cancer treatment, prevention, and screening: a report from the
      American Society of Clinical Oncology. J. Clin. Oncol. 25, 146-162.]. However,
      biobanks should not be considered a static activity. On the contrary, biobanking
      is a young discipline [Morente, M.M., Fernandez, P.L., de Alava, E. Biobanking:
      old activity or young discipline? Semin. Diagn. Pathol., in press.], which need
      continuously evolve according to the permanent development of new techniques and
      new scientific goals. To accomplish current requirements of the scientific
      community biobanks need to face some essential challenges including an
      appropriate design, harmonized and more suitable procedures, and sustainability,
      all of them in the framework of their ethic, legal and social dimensions. This
      review therefore presents an overview on these issues, based on the works and
      discussions of the Marble Arch International Working Group on Biobanking for
      Biomedical Research, integrated by experts in biobanking from five continents.

PMID- 19383343
TI  - Estradiol-estrogen receptor: a key interplay of the expression of syndecan-2 and
      metalloproteinase-9 in breast cancer cells.
AB  - Estrogens are related with the growth and development of target tissues and play
      a critical role in breast cancer progression. The effects of estrogens are
      mediated by the estrogen receptors ERalpha and ERbeta, which are members of the
      nuclear steroid receptor superfamily. To date, it is not known how these hormones
      elicit many of their effects on extracellular matrix molecules and how these
      effects can be connected with ER expression. For this purpose, the effect of
      estradiol on ER expression as well as on proteoglycan and metalloproteinase
      expression was studied. The effect of E2 on extracellular matrix molecule
      expression has been studied using ERalpha suppression in breast cancer cells. Our
      studies using ERalpha-positive MCF-7 cells show that estradiol affects the
      expression of syndecan-2, but not of syndecan-4, through ERalpha. Furthermore,
      the ability of estradiol to affect MMP-9 and TIMP-1 expression is connected with
      ERalpha status. Together, these data demonstrate the significant role of ERalpha
      on mediating the effect of estradiol on extracellular matrix molecules.

PMID- 19383344
TI  - TIMP-1 expression in human colorectal cancer is associated with TGF-B1, LOXL2,
      INHBA1, TNF-AIP6 and TIMP-2 transcript profiles.
AB  - The balance of activity between the endogenous enzyme inhibitors known as tissue
      inhibitors of metalloproteinases and their targets, the matrix
      metalloproteinases, in the extracellular matrix is thought to play an important
      role in tumour cell invasion. Supporting this notion, we have shown that
      colorectal cancer patients have increased plasma levels of the tissue inhibitor
      of metalloproteinases-1 (TIMP-1), and that high plasma TIMP-1 levels are
      associated with short colorectal cancer patient survival. However, although TIMP
      1 has been extensively studied in cancer, very little is known about how it is
      regulated. To further elucidate potential mechanisms of regulation of this
      protein, we did a number of experiments to look at associations between the
      transcript profile of TIMP-1 with known matrix metalloproteinases (MMPs) as well
      as with expression profiles of other genes differentially regulated in human
      colorectal cancer (CRC) and the other TIMPs 2-4, which have also been associated
      with the progression of colorectal cancer. Genome-wide expression profiling of
      172 CRC and normal mucosa samples was used to identify transcript changes for the
      genes under investigation. We found that TIMP-1 was up-regulated in CRC samples
      compared with normal tissue, while TIMP-2 was down-regulated. Eight MMPs were up
      regulated in CRC compared with normal tissue. Correlating up-regulated genes with
      the TIMP-1 transcript, we identified 13 that were also up-regulated in cancerous
      tissue. Among these were genes associated with the synthesis of extracellullar
      matrix, genes involved in the TGF-beta signalling pathway, and genes that are
      likely transcribed by the tumour cells. These insights add to the complex picture
      emerging about the regulation of TIMPs in colorectal cancer.

PMID- 19383345
TI  - Exon 2 deletion splice variant of gamma-glutamyl carboxylase causes des-gamma
      carboxy prothrombin production in hepatocellular carcinoma cell lines.
AB  - Using GGCX gene-specific real-time PCR, exon 2 deletion splice variant of vitamin
      K-dependent gamma-glutamyl carboxylase (GGCX) mRNA was identified in HCC cell
      lines. Expressions of wild type and exon 2 deletion variant of GGCX were analyzed
      with relevance to DCP production in HCC cell lines. Hep3B, HepG2, HuH1, HuH7, and
      PLC/PRF/5 produced DCP, while SK-Hep-1, HLE, HLF, and JHH1 produced no detectable
      level of DCP. DCP-producing cells expressed exon 2 deletion variant of GGCX mRNA
      and protein, while DCP-negative cells expressed no detectable level of exon 2
      deletion variant of GGCX. These results suggest that exon 2 deletion splice
      variant of GGCX causes dysfunction of GGCX enzyme activity resulting in DCP
      production in HCC cell lines.

PMID- 19383346
TI  - Impact of cytogenetic and genomic aberrations of the kallikrein locus in ovarian
      cancer.
AB  - The tissue kallikrein (KLK) genes are a new source for biomarkers in ovarian
      cancer. However, there has been no systematic analysis of copy number and
      structural rearrangements related to their protein expression. Chromosomal
      rearrangements and copy number changes of the KLK region were studied by FISH
      with protein levels measured by ELISA. Ovarian cancer and cell lines revealed the
      KLK region was subject to copy number imbalances or involved in unbalanced
      translocations and were associated with increased protein expression of KLKs 5,
      6, 7, 8, 9, 10 and 11. In this initial study, we introduce the potential for long
      range chromosomal effects and copy number as a mechanism for the previously
      reported aberrant expression of many KLK genes in ovarian cancers.

PMID- 19383347
TI  - MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous
      regression: a molecular portrait of stage 4S.
AB  - Stage 4 neuroblastoma (NB) are heterogeneous regarding their clinical
      presentations and behavior. Indeed infants (stage 4S and non-stage 4S of age
      <365days at diagnosis) show regression contrasting with progression in children
      (>365days). Our study aimed at: (i) identifying age-based genomic and gene
      expression profiles of stage 4 NB supporting this clinical stratification; and
      (ii) finding a stage 4S NB signature. Differential genome and transcriptome
      analyses of a learning set of MYCN-non amplified stage 4 NB tumors at diagnosis
      (n=29 tumors including 12 stage 4S) were performed using 1Mb BAC microarrays and
      Agilent 22K probes oligo-microarrays. mRNA chips data following filtering yielded
      informative genes before supervised hierarchical clustering to identify
      relationship among tumor samples. After confirmation by quantitative RT-PCR, a
      stage 4S NB's gene cluster was obtained and submitted to a validation set (n=22
      tumors). Genomic abnormalities of infant's tumors (whole chromosomes gains or
      loss) differ radically from that of children (intra-chromosomal rearrangements)
      but could not discriminate infants with 4S from those without this presentation.
      In contrast, differential gene expression by looking at both individual genes and
      whole biological pathways leads to a molecular stage 4S NB portrait which
      provides new biological clues about this fascinating entity.

PMID- 19383350
TI  - The flat-funding years and the National Cancer Institute: consequences for cancer
      research.

PMID- 19383348
TI  - The chemokine interleukin-8 and the surface activation protein CD69 are markers
      for Bcr-Abl activity in chronic myeloid leukemia.
AB  - We have identified differentially regulated genes in chronic myeloid leukemia
      (CML) cells upon short treatment with the broad-spectrum Bcr-Abl inhibitor
      dasatinib. The highly specific Bcr-Abl inhibitor nilotinib caused a very similar
      gene expression signature, validating the identified differentially regulated
      genes as a read-out of Bcr-Abl activity and implying that Bcr-Abl is the
      functionally central target of dasatinib in CML cells. Among the strongest
      downregulated genes, we have further validated the activation marker CD69 and the
      chemokine interleukin (IL)-8. Expression of both proteins is upregulated upon Bcr
      Abl expression and inhibited by dasatinib and nilotinib. IL-8 may thus be a
      useful marker for the monitoring of CML inhibitor efficacy and play a potential
      pathophysiological role in CML.

PMID- 19383351
TI  - Gender bias remains prevalent in the biological sciences.

PMID- 19383352
TI  - Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast
      cancer: MRE11 as a candidate familial cancer-predisposing gene.
AB  - The MRE11, RAD50, and NBS1 genes encode proteins of the MRE11-RAD50-NBS1 (MRN)
      complex critical for proper maintenance of genomic integrity and tumour
      suppression; however, the extent and impact of their cancer-predisposing defects,
      and potential clinical value remain to be determined. Here, we report that among
      a large series of approximately 1000 breast carcinomas, around 3%, 7% and 10%
      tumours showed aberrantly reduced protein expression for RAD50, MRE11 and NBS1,
      respectively. Such defects were more frequent among the ER/PR/ERBB2 triple
      negative and higher-grade tumours, among familial (especially BRCA1/BRCA2
      associated) rather than sporadic cases, and the NBS1 defects correlated with
      shorter patients' survival. The BRCA1-associated and ER/PR/ERBB2 triple-negative
      tumours also showed high incidence of constitutively active DNA damage signalling
      (gammaH2AX) and p53 aberrations. Sequencing the RAD50, MRE11 and NBS1 genes of 8
      patients from non-BRCA1/2 breast cancer families whose tumours showed concomitant
      reduction/loss of all three MRN-complex proteins revealed two germline mutations
      in MRE11: a missense mutation R202G and a truncating mutation R633STOP (R633X).
      Gene transfer and protein analysis of cell culture models with mutant MRE11
      implicated various destabilization patterns among the MRN complex proteins
      including NBS1, the abundance of which was restored by re-expression of wild-type
      MRE11. We propose that germline mutations qualify MRE11 as a novel candidate
      breast cancer susceptibility gene in a subset of non-BRCA1/2 families. Our data
      have implications for the concept of the DNA damage response as an intrinsic anti
      cancer barrier, various components of which become inactivated during cancer
      progression and also represent the bulk of breast cancer susceptibility genes
      discovered to date.

PMID- 19383353
TI  - Curcumin in combination with bortezomib synergistically induced apoptosis in
      human multiple myeloma U266 cells.
AB  - Growth of multiple myeloma cells is controlled by various factors derived from
      host bone marrow microenvironments. Interaction between multiple myeloma cells
      and bone marrow stromal cells (BMSCs) plays an important role in the expression
      of adhesive molecules and secretion of growth factors involved in multiple
      myeloma (MM) cell growth, survival, and resistance to anticancer drugs. Recently,
      the possibility of developing novel anti-cancer therapeutic strategies targeting
      both MM cells and MM cell-BMSC interactions has been discussed. Here we present
      data showing that curcumin, a major constituent of turmeric compounds extracted
      from the rhizomes of the plant Curcuma longa, effectively reduced the growth of
      MM cells and BMSCs. Upon treatment with curcumin, IL-6/sIL-6R-induced STAT3 and
      Erk phosphorylation was dramatically reduced in the co-cultured cells. In
      addition, curcumin inhibited the production of pro-inflammatory cytokines and
      VEGF, factors that are associated with the progression of multiple myeloma, from
      both MM cells and BMSCs. In a combination treatment with curcumin and bortezomib,
      IL-6/sIL-6R-induced STAT3 and Erk phosphorylation was effectively inhibited.
      Moreover, this combination treatment synergistically inhibited the growth of MM
      cells co-cultured with BMSCs as compared to controls. Taken together, these
      results indicate that curcumin potentiates the therapeutic efficacy of bortezomib
      in MM suggesting this combination therapy to be of value in the clinical
      management of MM.

PMID- 19383355
TI  - Nemosis of fibroblasts is inhibited by benign HaCaT keratinocytes but promoted by
      malignant HaCaT cells.
AB  - Cell-cell clustering of fibroblasts, called nemosis, leads to a massive growth
      factor, proteolytic and proinflammatory response. Culturing fibroblasts in
      conditioned medium collected from HaCaT keratinocyte cell panel representing
      different stages of skin carcinogenesis had a differential effect on fibroblast
      nemosis. Non-malignant keratinocytes had a nemosis-inhibiting effect on
      fibroblasts as seen by inhibition of COX-2 protein expression. Conditioned medium
      from malignant cells promoted fibroblast nemosis by inducing higher levels of COX
      2, HGF/SF and VEGF. Even a small amount of malignant medium converted the
      inhibitory effect of benign medium, whereas non-malignant medium neutralized the
      nemosis-promoting effect of malignant medium. In collagen co-cultures benign
      keratinocytes caused a nemosis-inhibiting effect on fibroblast spheroids by
      inhibiting COX-2 induction, while with malignant keratinocytes myofibroblastic
      differentiation of fibroblasts was seen.

PMID- 19383354
TI  - CAMK1D amplification implicated in epithelial-mesenchymal transition in basal
      like breast cancer.
AB  - Breast cancer exhibits clinical and molecular heterogeneity, where expression
      profiling studies have identified five major molecular subtypes. The basal-like
      subtype, expressing basal epithelial markers and negative for estrogen receptor
      (ER), progesterone receptor (PR) and HER2, is associated with higher overall
      levels of DNA copy number alteration (CNA), specific CNAs (like gain on
      chromosome 10p), and poor prognosis. Discovering the molecular genetic basis of
      tumor subtypes may provide new opportunities for therapy. To identify the driver
      oncogene on 10p associated with basal-like tumors, we analyzed genomic profiles
      of 172 breast carcinomas. The smallest shared region of gain spanned just seven
      genes at 10p13, including calcium/calmodulin-dependent protein kinase ID
      (CAMK1D), functioning in intracellular signaling but not previously linked to
      cancer. By microarray, CAMK1D was overexpressed when amplified, and by
      immunohistochemistry exhibited elevated expression in invasive carcinomas
      compared to carcinoma in situ. Engineered overexpression of CAMK1D in non
      tumorigenic breast epithelial cells led to increased cell proliferation, and
      molecular and phenotypic alterations indicative of epithelial-mesenchymal
      transition (EMT), including loss of cell-cell adhesions and increased cell
      migration and invasion. Our findings identify CAMK1D as a novel amplified
      oncogene linked to EMT in breast cancer, and as a potential therapeutic target
      with particular relevance to clinically unfavorable basal-like tumors.

PMID- 19383356
TI  - Circulating tumour cells as a predictive factor for response to systemic
      chemotherapy in patients with advanced colorectal cancer.
AB  - Circulating tumour cells (CTC) can be traced in patients with different types of
      cancer. The aim of this study was to detect CTC in patients with advanced
      colorectal cancer and whether CTC are still detectable after systemic
      chemotherapy. Blood from 34 patients with advanced colorectal cancer was analysed
      for the presence of CTC before chemotherapy was given and after 3 months. Eleven
      patients demonstrated a tumour remission after chemotherapy. In 6 cases CTC were
      detectable before but not after initiation of chemotherapy. Ten patients
      demonstrated a progression. In 5 cases CTC were detected before and after
      chemotherapy. Our data suggest that the detection of CTC will help to identify
      patients responding to chemotherapy or with a risk of a therapy failure.

PMID- 19383357
TI  - The CALM and CALM/AF10 interactor CATS is a marker for proliferation.
AB  - The CATS protein was recently identified as a novel CALM interacting protein.
      CATS increases the nuclear and specifically the nucleolar localization of the
      leukemogenic CALM/AF10 fusion protein. We cloned and characterized the murine
      Cats gene. Detailed analysis of murine Cats expression during mouse embryogenesis
      showed an association with rapidly proliferating tissues. Interestingly, the Cats
      transcript is highly expressed in murine hematopoietic cells transformed by
      CALM/AF10. The CATS protein is highly expressed in leukemia, lymphoma and tumor
      cell lines but not in non-proliferating T-cells or human peripheral blood
      lymphocytes. CATS protein levels are cell cycle dependent and it is induced by
      mitogens, suggesting a role of CATS in the control of cell proliferation and
      possibly CALM/AF10-mediated leukemogenesis.

PMID- 19383360
TI  - Profile: Professor Axel Ullrich.

PMID- 19383358
TI  - A single lysis solution for the analysis of tissue samples by different proteomic
      technologies.
AB  - Cancer, being a major healthcare concern worldwide, is one of the main targets
      for the application of emerging proteomic technologies and these tools promise to
      revolutionize the way cancer will be diagnosed and treated in the near future.
      Today, as a result of the unprecedented advances that have taken place in
      molecular biology, cell biology and genomics there is a pressing need to
      accelerate the translation of basic discoveries into clinical applications. This
      need, compounded by mounting evidence that cellular model systems are unable to
      fully recapitulate all biological aspects of human dissease, is driving
      scientists to increasingly use clinically relevant samples for biomarker and
      target discovery. Tissues are heterogeneous and as a result optimization of
      sample preparation is critical for generating accurate, representative, and
      highly reproducible quantitative data. Although a large number of protocols for
      preparation of tissue lysates has been published, so far no single recipe is able
      to provide a "one-size fits all" solubilization procedure that can be used to
      analyse the same lysate using different proteomics technologies. Here we present
      evidence showing that cell lysis buffer 1 (CLB1), a lysis solution commercialized
      by Zeptosens [a division of Bayer (Schweiz) AG], provides excellent sample
      solubilization and very high 2D PAGE protein resolution both when using carrier
      ampholytes and immobilized pH gradient strips. Moreover, this buffer can also be
      used for array-based proteomics (reverse-phase lysate arrays or direct antibody
      arrays), allowing the direct comparison of qualitative and quantitative data
      yielded by these technologies when applied to the same samples. The usefulness of
      the CLB1 solution for gel-based proteomics was further established by 2D PAGE
      analysis of a number of technically demanding specimens such as breast carcinoma
      core needle biopsies and problematic tissues such as brain cortex, cerebellum,
      skeletal muscle, kidney cortex and tongue. This solution when combined with a
      specific sample preparation technique - cryostat sectioning of frozen specimens -
      simplifies tissue sample preparation and solves most of the difficulties
      associated with the integration of data generated by different proteomic
      technologies.

PMID- 19383361
TI  - Turning the Stockholm Declaration into reality: Creating a world-class
      infrastructure for cancer research in Europe.

PMID- 19383362
TI  - Report on EU-USA workshop: how systems biology can advance cancer research (27
      October 2008).
AB  - The main conclusion is that systems biology approaches can indeed advance cancer
      research, having already proved successful in a very wide variety of cancer
      related areas, and are likely to prove superior to many current research
      strategies. Major points include: Systems biology and computational approaches
      can make important contributions to research and development in key clinical
      aspects of cancer and of cancer treatment, and should be developed for
      understanding and application to diagnosis, biomarkers, cancer progression, drug
      development and treatment strategies. Development of new measurement technologies
      is central to successful systems approaches, and should be strongly encouraged.
      The systems view of disease combined with these new technologies and novel
      computational tools will over the next 5-20 years lead to medicine that is
      predictive, personalized, preventive and participatory (P4 medicine).Major
      initiatives are in progress to gather extremely wide ranges of data for both
      somatic and germ-line genetic variations, as well as gene, transcript, protein
      and metabolite expression profiles that are cancer-relevant. Electronic databases
      and repositories play a central role to store and analyze these data. These
      resources need to be developed and sustained. Understanding cellular pathways is
      crucial in cancer research, and these pathways need to be considered in the
      context of the progression of cancer at various stages. At all stages of cancer
      progression, major areas require modelling via systems and developmental biology
      methods including immune system reactions, angiogenesis and tumour progression.A
      number of mathematical models of an analytical or computational nature have been
      developed that can give detailed insights into the dynamics of cancer-relevant
      systems. These models should be further integrated across multiple levels of
      biological organization in conjunction with analysis of laboratory and clinical
      data.Biomarkers represent major tools in determining the presence of cancer, its
      progression and the responses to treatments. There is a need for sets of high
      quality annotated clinical samples, enabling comparisons across different
      diseases and the quantitative simulation of major pathways leading to biomarker
      development and analysis of drug effects.Education is recognized as a key
      component in the success of any systems biology programme, especially for
      applications to cancer research. It is recognized that a balance needs to be
      found between the need to be interdisciplinary and the necessity of having
      extensive specialist knowledge in particular areas.A proposal from this workshop
      is to explore one or more types of cancer over the full scale of their
      progression, for example glioblastoma or colon cancer. Such an exemplar project
      would require all the experimental and computational tools available for the
      generation and analysis of quantitative data over the entire hierarchy of
      biological information. These tools and approaches could be mobilized to
      understand, detect and treat cancerous processes and establish methods applicable
      across a wide range of cancers.

PMID- 19383363
TI  - 'Tackling cancer in the EU: the role of innovation'.
AB  - The objective of the workshop was to examine what Cancer Innovation in Europe
      means and what it should be standing for in the future. The panel discussion
      brought together patients, researchers, politicians and industry in order to
      examine what cancer innovation represents to them, what the challenges are to
      innovation, and how innovation in this research area can be encouraged and
      developed in the EU.

PMID- 19383364
TI  - Biomarkers in oncology drug development.
AB  - Biomarker measurements have become an essential component of oncology drug
      development, particularly so in this era of targeted therapies. Such measurements
      ensure that clinical studies are testing our biological hypotheses and can help
      make the difficult decisions required to choose which drugs to stop developing or
      de-prioritise. For those drugs taken forward, biomarker measurements may also
      help choose the appropriate dose, schedule and patient population. In this review
      we discuss the intrinsic properties of biological sample based efficacy
      measurements and how these relate to their implementation in oncology drug
      development by way of points to consider and examples.

PMID- 19383365
TI  - Targeted proteomic strategy for clinical biomarker discovery.
AB  - The high complexity and large dynamic range of blood plasma proteins currently
      prohibit the sensitive and high-throughput profiling of disease and control
      plasma proteome sample sets large enough to reliably detect disease indicating
      differences. To circumvent these technological limitations we describe here a new
      two-stage strategy for the mass spectrometry (MS) assisted discovery,
      verification and validation of disease biomarkers. In an initial discovery phase
      N-linked glycoproteins with distinguishable expression patterns in primary normal
      and diseased tissue are detected and identified. In the second step the proteins
      identified in the initial phase are subjected to targeted MS analysis in plasma
      samples, using the highly sensitive and specific selected reaction monitoring
      (SRM) technology. Since glycosylated proteins, such as those secreted or shed
      from the cell surface are likely to reside and persist in blood, the two-stage
      strategy is focused on the quantification of tissue derived glycoproteins in
      plasma. The focus on the N-glycoproteome not only reduces the complexity of the
      analytes, but also targets an information-rich subproteome which is relevant for
      remote sensing of diseases in the plasma. The N-glycoprotein based biomarker
      discovery and validation workflow reviewed here allows for the robust
      identification of protein candidate panels that can finally be selectively
      monitored in the blood plasma at high sensitivity in a reliable, non-invasive and
      quantitative fashion.

PMID- 19383366
TI  - Expression and hypoxic up-regulation of neuroglobin in human glioblastoma cells.
AB  - Neuroglobin is a recently identified globin molecule that is expressed
      predominantly in the vertebrate brain. Neuroglobin expression increases in oxygen
      deprived neurons, suggesting it protects neurons from ischemic cell death. We
      report that neuroglobin transcript and protein are expressed in human
      glioblastoma cells, and that this expression increases in hypoxia in vitro. We
      also show that neuroglobin is up-regulated in hypoxic microregions of
      glioblastoma tumor xenografts. Our finding of hypoxic up-regulation of
      neuroglobin in human glioblastoma cells may provide insight into how tumor cells
      adapt to and survive in hypoxic microenvironments.

PMID- 19383367
TI  - PCDH24-induced contact inhibition involves downregulation of beta-catenin
      signaling.
AB  - Elevated expression of the protocadherin LKC (PCDH24) in HCT116 colon carcinoma
      cells has been shown to induce contact inhibition, thereby completely abolishing
      tumor formation in vivo (Carcinogenesis, 2002; 23(7):1139-1148). To clarify the
      molecular mechanism behind this effect, we performed 2-DE/MS and DNA microarray
      analyses in order to compare protein and gene expression patterns of parental
      HCT116 and PCDH24-expressing HTC116 derivative cells. The data revealed drastic
      changes in phenotypic markers between parental and PCDH24-expressing cells. We
      found that in PCDH24-expressing cells beta-catenin, a major player in TCF/lef
      signaling, is retained in a submembranous location. beta-catenin retention
      coincided with a subsequent decrease in downstream targets of beta-catenin such
      as CD44, PLAUR, Myc, cyclin D1 and Met. From these findings we propose a novel
      model for the suppression of beta-catenin signaling by PCDH24 that leads to
      contact inhibition.

PMID- 19383368
TI  - HBx genotype D represses GSTP1 expression and increases the oxidative level and
      apoptosis in HepG2 cells.
AB  - Epigenetics has been implicated in human cancer development. Epigenetic factors
      include HBx protein, which is able to induce hypermethylation and suppresses
      tumor suppressor genes. One of such tumor suppressor genes, GSTP1, shows reduced
      expression in many human cancers. Hypermethylation of GSTP1 is the most studied
      mechanism of its silence. In the present study, we reported that GSTP1 expression
      was completely depleted in HBV integrated HepG2.2.15 cells due to the
      hypermethylation in its promoter region. And it was HBx, especially HBx genotype
      D, that played the key role in repressing GSTP1 expression. Further functional
      studies like ROS assay and apoptosis detection were also used to confirm this
      repression. Our findings should facilitate the understanding of HBV and their
      influences on the epigenetic modulations for epigenetic tumorigenesis during HBV
      mediated hepatocellular carcinogenesis.

PMID- 19383371
TI  - Profile: Professor John Mendelsohn.

PMID- 19383369
TI  - Ebselen abrogates TNFalpha induced pro-inflammatory response in glioblastoma.
AB  - We investigated the pro-inflammatory response mediated by TNFalpha in
      glioblastoma and whether treatment with organoselenium Ebselen (2-phenyl-1,2
      benzisoselenazol-3[2H]one) can affect TNFalpha induced inflammatory response.
      Exposure to TNFalpha increased the expression of pro-inflammatory mediator
      interleukin IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and
      cyclooxygenase (COX-2). Treatment with Ebselen abrogated TNFalpha induced
      increase in pro-inflammatory mediators. Ebselen not only abrogated TNFalpha
      induced enhanced invasiveness of glioma cells by down-regulating matrix metallo
      proteinase (MMP-9) and urokinase plasminogen (uPa) activity, but also inhibited
      glioma cell migration. Treatment with Ebselen also down-regulated the enhanced
      ROS production of TNFalpha treated glioma cells. In addition, Ebselen induced DNA
      damage repair signaling response in glioma cells both in the presence and absence
      of TNFalpha. These studies indicate that together with its known ability to
      sensitize glioma cell to TNFalpha induced apoptosis, Ebselen can overcome
      TNFalpha induced pro-inflammatory mediators to prevent a build up of a
      deleterious pro-inflammatory tumor microenvironment.

PMID- 19383372
TI  - The Bayh-Dole Act: a model for promoting research translation?
AB  - The Bayh-Dole Act of 1980 was passed with the intention of promoting research
      into cancer and other diseases by providing institutions and researchers with a
      commercial incentive, even though much of their work was publicly funded. Now,
      many are questioning whether the system has worked as promised and some warn it
      may be jeopardizing the pursuit of science with no direct market relevance.

PMID- 19383373
TI  - Thematic issue on the molecular biology of hereditary ovarian cancer. Preface.

PMID- 19383375
TI  - The contribution of BRCA1 and BRCA2 to ovarian cancer.
AB  - Germline mutations of the BRCA1 and BRCA2 genes confer a high life-time risk of
      ovarian cancer. They represent the most significant and well characterised
      genetic risk factors so far identified for the disease. The frequency with which
      BRCA1/2 mutations occur in families containing multiple cases of ovarian cancer
      or breast and ovarian cancer, and in population-based ovarian cancer series
      varies geographically and between different ethnic groups. There are differences
      in the frequency of common mutations and in the presence of specific founder
      mutations in different populations. BRCA1 and BRCA2 are responsible for half of
      all families containing two or more ovarian cancer cases. In population-based
      studies, BRCA1 and BRCA2 mutations are present in 5-15% of all ovarian cancer
      cases. Often, individuals in which mutations are identified in unselected cases
      have no family history of either ovarian or breast cancer. The ability to
      identify BRCA1/2 mutations has been one of the few major success stories over the
      last few years in the clinical management of ovarian cancer. Currently,
      unaffected individuals can be screened for mutations if they have a family
      history of the disease. If a mutation is identified in the family, and if an
      individual is found be a mutation carrier, they can be offered clinical
      intervention strategies that can dramatically reduce their ovarian cancer risks.
      In some populations with frequent founder mutations screening may not be
      dependent on whether a mutation is identified in an affected relative.

PMID- 19383376
TI  - Molecular profiles of hereditary epithelial ovarian cancers and their
      implications for the biology of this disease.
AB  - BRCA1 and BRCA2 germline mutations account for the majority of hereditary ovarian
      cancers and comprise 10% of total cases. Ovarian cancers arising from these
      mutations exhibit both overlapping and distinct clinical and molecular features.
      The expression profiles of sporadic ovarian cancers show similarities to those of
      BRCA1 and BRCA2-related tumors suggesting that BRCA-related pathways may be
      involved in their development as well. The purpose of this review is to consider
      the available data on ovarian cancers in the context of other investigations of
      BRCA-related transcriptional alterations, and highlight areas for future
      research.

PMID- 19383377
TI  - Large-scale genomic analysis of ovarian carcinomas.
AB  - Epithelial ovarian cancers are typified by frequent genomic aberrations that have
      been difficult to unravel. Recently, high-resolution array technologies have
      provided the first glimpse of the remarkable complexity of these aberrations with
      some ovarian cancers containing hundreds of copy number breakpoints, micro
      deletions and amplifications. Many of these alterations contain cancer-related
      genes suggesting that the majority is disease-associated and not just the product
      of random genomic instability. Future developments such as next-generation
      sequencing and integrated analysis of data from multiple array platforms on large
      numbers of samples are poised to revolutionize our understanding of this complex
      disease.

PMID- 19383378
TI  - Intercepting pelvic cancer in the distal fallopian tube: theories and realities.
AB  - The pathogenesis of high-grade serous carcinoma of the ovary has come into
      sharper focus as closer attention has been paid to the earlier phases of this
      disease. The study of patients with BRCA mutation has been of particular value,
      in as much as the examination of prophylactic salpingo-oophorectomies will reveal
      an early cancer in approximately 5% of individuals. Recently studies have shown
      that about 80% of these early carcinomas originate in the distal fallopian tube.
      This review summarizes the recent data supporting the distal fallopian tube as an
      important site for serous carcinogenesis, stressing both the presence of a novel
      precursor (the p53 signature) and the application of this model to all women
      irrespective of BRCA status. The challenges and unmet needs unmasked by this
      paradigm shift in ovarian cancer research are discussed.

PMID- 19383374
TI  - Hereditary ovarian carcinoma: heterogeneity, molecular genetics, pathology, and
      management.
AB  - Hereditary ovarian cancer accounts for at least 5% of the estimated 22,000 new
      cases of this disease during 2009. During this same time, over 15,000 will die
      from malignancy ascribed to ovarian origin. The bulk of these hereditary cases
      fits the hereditary breast-ovarian cancer syndrome, while virtually all of the
      remainder will be consonant with the Lynch syndrome, disorders which are
      autosomal dominantly inherited. Advances in molecular genetics have led to the
      identification of BRCA1 and BRCA2 gene mutations which predispose to the
      hereditary breast-ovarian cancer syndrome, and mutations in mismatch repair
      genes, the most common of which are MSH2 and MLH1, which predispose to Lynch
      syndrome. These discoveries enable relatively certain diagnosis, limited only by
      their variable penetrance, so that identification of mutation carriers through a
      comprehensive cancer family history might be possible. This paper reviews the
      subject of hereditary ovarian cancer, with particular attention to its molecular
      genetic basis, its pathology, and its phenotypic/genotypic heterogeneity.

PMID- 19383380
TI  - Inaugural issue of Stem Cell Research.

PMID- 19383379
TI  - Role of genetic polymorphisms and ovarian cancer susceptibility.
AB  - The value of identifying women with an inherited predisposition to epithelial
      ovarian cancer has become readily apparent with the identification of the BRCA1,
      and BRCA2 genes. Women who inherit a deleterious mutation in either of these
      genes have a very high lifetime risk of ovarian cancer (10-60%) and to some
      extent, increased risks of fallopian tube and peritoneal cancer. These highly
      lethal cancers are almost completely prevented by prophylactic
      salpingoophorectomy. BRCA1/2 mutation testing has become the accepted standard of
      care in families with a strong history of breast and/or ovarian cancer. This
      approach has the potential to reduce ovarian cancer mortality by about 10%.
      Although the ability to perform genetic testing for BRCA1 and 2 represents a
      significant clinical advance, the frequency of mutations in these high penetrance
      ovarian cancer susceptibility genes is low in most populations. There is evidence
      to suggest that ovarian cancer susceptibility might be affected by common low
      penetrance genetic polymorphisms like it was shown for several common disorders
      like diabetes or breast cancer. Although such polymorphisms would increase risk
      to a lesser degree, they could contribute to the development of a greater
      proportion of ovarian cancers by virtue of their higher frequencies in the
      population. It has been shown that the most powerful approach to studying low
      penetrance genes is an association study rather than a linkage study design. This
      review describes the efforts that have been made in this field by individual case
      control studies and through multi-center collaborations as part of international
      consortia such as the Ovarian Cancer Association Consortium (OCAC).

PMID- 19383381
TI  - Time to mend a broken heart.

PMID- 19383382
TI  - Proteome biology of stem cells.
AB  - The notion that integration of cutting-edge technologies in stem cell research
      would be enhanced by proteomic analyses has emanated from rapid advances in
      proteome technology. These advances have increased the probability that basic
      properties of stem cells will be elucidated more effectively, leading to
      acceleration toward novel stem cell therapies. We have therefore sought to
      establish a world-wide alliance of proteomics and stem cell researchers, which
      has resulted in the foundation of an initiative supported by the Human Proteome
      Organisation (HUPO) and the International Society for Stem Cell Research (ISSCR)
      called the Proteome Biology of Stem Cells Initiative. Here we report on the
      rationale and goals of this initiative.

PMID- 19383383
TI  - Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse
      heart and transiently improve function after myocardial infarction.
AB  - Regeneration of the myocardium by transplantation of cardiomyocytes is an
      emerging therapeutic strategy. Human embryonic stem cells (HESC) form
      cardiomyocytes readily but until recently at low efficiency, so that preclinical
      studies on transplantation in animals are only just beginning. Here, we show the
      results of the first long-term (12 weeks) analysis of the fate of HESC-derived
      cardiomyocytes transplanted intramyocardially into healthy, immunocompromised
      (NOD-SCID) mice and in NOD-SCID mice that had undergone myocardial infarction
      (MI). Transplantation of mixed populations of differentiated HESC containing 20
      25% cardiomyocytes in control mice resulted in rapid formation of grafts in which
      the cardiomyocytes became organized and matured over time and the
      noncardiomyocyte population was lost. Grafts also formed in mice that had
      undergone MI. Four weeks after transplantation and MI, this resulted in
      significant improvement in cardiac function measured by magnetic resonance
      imaging. However, at 12 weeks, this was not sustained despite graft survival.
      This suggested that graft size was still limiting despite maturation and
      organization of the transplanted cells. More generally, the results argued for
      requiring a minimum of 3 months follow-up in studies claiming to observe improved
      cardiac function, independent of whether HESC or other (adult) cell types are
      used for transplantation.

PMID- 19383384
TI  - Endocrine cells develop within pancreatic bud-like structures derived from mouse
      ES cells differentiated in response to BMP4 and retinoic acid.
AB  - We have examined factors affecting the in vitro differentiation of Pdx1(GFP/w)
      ESCs to pancreatic endocrine cells. Inclusion of Bone Morphogenetic Protein 4
      (BMP4) during the first four days of differentiation followed by a 24-hour pulse
      of retinoic acid (RA) induced the formation of GFP(+) embryoid bodies (EBs). GFP
      expression was restricted to E-cadherin(+) tubes and GFP bright (GFP(br)) buds,
      reminiscent of GFP(+) early foregut endoderm and GFP(br) pancreatic buds observed
      in Pdx1(GFP/w) embryos. These organoid structures developed without further
      addition of exogenous factors between days 5 and 12, suggesting that day 5 EBs
      contained a template for the subsequent phase of development. EBs treated with
      nicotinamide after day 12 of differentiation expressed markers of endocrine and
      exocrine differentiation, but only in cells within the GFP(br) buds. Analysis of
      Pdx1(GFP/w) ESCs modified by targeting a dsRed1 gene to the Ins1 locus
      (Pdx1(GFP/w)Ins1(RFP/w) ESCs) provided corroborating evidence that insulin
      positive cells arose from GFP(br) buds, mirroring the temporal relationship
      between pancreatic bud development and the formation of endocrine cells in the
      developing embryo. The readily detectable co-expression of GFP and RFP in grafts
      derived from transplanted EBs demonstrated the utility of Pdx1(GFP/w)Ins1(RFP/w)
      ESCs for investigating pancreatic differentiation in vitro and in vivo.

PMID- 19383385
TI  - Monetary payments for the procurement of oocytes for stem cell research: In
      search of ethical and political consistency.
AB  - The debate on both the appropriateness of allowing healthy women to provide
      oocytes for research use and the use of financial incentives is increasingly
      reduced to a confrontation between ethics, science, and the welfare of women. It
      is plausible that the expansion of national and international research efforts,
      paired with the growing trend toward liberalizing stem cell research policies,
      will inevitably result in increased demand for the materials needed to conduct
      such research. The scarcity of human reproductive materials that are available
      for research generates concerns over, the emergence of a "black market", an
      increase in financial incentives for donors, and the appropriateness of current
      regulatory frameworks that aim to safeguard donors. In this article we explore
      the conceptual models for categorizing oocyte donors and analyze the use of
      financial incentives as well as the compensation models proposed and implemented
      in various jurisdictions. Finally, we propose the adoption of a mixed model that
      both respects altruism and provides a feasible solution to an issue that could be
      situated only in the context of the overall acceptability of providing financial
      rewards to donors of human reproductive materials for assisted reproductive
      technologies.

PMID- 19383386
TI  - Differentiation is coupled to changes in the cell cycle regulatory apparatus of
      human embryonic stem cells.
AB  - Mouse embryonic stem cells (mESC) exhibit cell cycle properties entirely distinct
      from those of somatic cells. Here we investigated the cell cycle characteristics
      of human embryonic stem cells (hESC). HESC could be sorted into populations based
      on the expression level of the cell surface stem cell marker GCTM-2. Compared to
      mESC, a significantly higher proportion of hESC (GCTM-2(+) Oct-4(+) cells)
      resided in G(1) and retained G(1)-phase-specific hypophosphorylated
      retinoblastoma protein (pRb). We showed that suppression of traverse through G(1)
      is sufficient to promote hESC differentiation. Like mESC, hESC expressed cyclin E
      constitutively, were negative for D-type cyclins, and did not respond to CDK-4
      inhibition. By contrast, cyclin A expression was periodic in hESC and coincided
      with S and G(2)/M phase progression. FGF-2 acted solely to sustain hESC
      pluripotency rather than to promote cell cycle progression or inhibit apoptosis.
      Differentiation increased G(1)-phase content, reinstated cyclin D activity, and
      restored the proliferative response to FGF-2. Treatment with CDK-2 inhibitor
      delayed hESC in G(1) and S phase, resulting in accumulation of cells with
      hypophosphorylated pRb, GCTM-2, and Oct-4 and, interestingly, a second pRb(+)
      GCTM-2(+) subpopulation lacking Oct-4. We discuss evidence for a G(1)-specific,
      pRb-dependent restriction checkpoint in hESC closely associated with the
      regulation of pluripotency.

PMID- 19383387
TI  - Apoptosis of male germ-line stem cells after laser ablation of their niche.
AB  - Male germ-line stem cells (GSCs) and their niche-the apical cells or hub cells
      display a unique feature at the apices of insect testicular follicles. In the
      locust, Locusta migratoria, the niche consists of only one large apical cell
      surrounded by about 60 GSCs. The apical cell can be readily identified in the
      intact follicle. Using laser ablation it is feasible to destroy the apical cell
      exclusively without injuring neighboring GSCs or any other cells. The most
      immediate effect on GSCs is the loss of their structural polarity. Beginning
      about 3 h after laser treatment chromatin starts to clump and condense in
      individual GSCs, and some show the first signs of cellular breakdown. These
      symptoms intensify during the 96-h observation period after laser ablation of the
      apical cell. TUNEL staining and electron microscopic observations confirm an
      apoptotic cell death of the GSCs. Laser ablation of individual GSCs had no effect
      on neighboring GSCs or the apical cell. Destroyed apical cells were not replaced
      during the observation period. Mitotic divisions of GSCs ceased after about 24 h
      after apical cell ablation. It is speculated that it might be a general principle
      in stem cell-niche relationships that stem cells undergo apoptosis when the niche
      is dysfunctional. This could be a control mechanism to prevent tumor growth of
      orphaned GSCs.

PMID- 19383388
TI  - In this issue...

PMID- 19383389
TI  - Signaling networks in hepatic oval cell activation.
AB  - Oval cells are hypothesized to be the progeny of intrahepatic stem cells, also
      referred to as adult liver stem cells. The mechanisms by which these cells are
      activated to proliferate and differentiate during liver regeneration is important
      for the development of new therapies to treat liver disease. Oval cell activation
      is the first step in progenitor-dependent liver regeneration in response to
      certain types of injury. This review describes what is currently known about the
      factors involved in oval cell activation, proliferation, migration, and
      differentiation.

PMID- 19383390
TI  - On the road to reprogramming.

PMID- 19383391
TI  - Heterogeneity of pluripotent marker gene expression in colonies generated in
      human iPS cell induction culture.
AB  - Induction of pluripotent stem cells from human fibroblasts has been achieved by
      the ectopic expression of two different sets of four genes. However, the
      mechanism of the pluripotent stem cell induction has not been elucidated. Here we
      identified a marked heterogeneity in colonies generated by the four-gene (Oct3/4,
      Sox2, c-Myc, and Klf4) transduction method in human neonatal skin-derived cells.
      The four-gene transduction gave a higher probability of induction for archetypal
      pluripotent stem cell marker genes (Nanog, TDGF, and Dnmt3b) than for marker
      genes that are less specific for pluripotent stem cells (CYP26A1 and TERT) in
      primary induction culture. This tendency may reflect the molecular mechanism
      underlying the induction of human skin-derived cells into pluripotent stem cells.
      Among the colonies induced by the four-gene transduction, small cells with a high
      nucleus-to-cytoplasm ratio could be established by repeated cloning. Subsequently
      established cell lines were similar to human embryonic stem cells as well as
      human induced pluripotent stem (iPS) cells derived from adult tissue in
      morphology, gene expression, long-term self-renewal ability, and teratoma
      formation. Genome-wide single-nucleotide polymorphism array analysis of the human
      iPS cell line indicates that the induction process did not induce DNA mutation.

PMID- 19383392
TI  - p53 is required for etoposide-induced apoptosis of human embryonic stem cells.
AB  - The molecular mechanisms controlling DNA-damage-induced apoptosis of human
      embryonic stem cells (hESC) are poorly understood. Here we investigate the role
      of p53 in etoposide-induced apoptosis. We show that p53 is constitutively
      expressed at high levels in the cytoplasm of hESC. Etoposide treatment results in
      a rapid and extensive induction of apoptosis and leads to a further increase in
      p53 and PUMA expression as well as Bax processing. p53 both translocates to the
      nucleus and associates with the mitochondria, accompanied by colocalization of
      Bax with Mcl1. hESC stably transduced with p53 shRNA display 80% reduction of
      endogenous p53 and exhibit an 80% reduction in etoposide-induced apoptosis
      accompanied by constitutive downregulation of Bax and an attenuated upregulation
      of PUMA. Our data further show that undifferentiated hESC that express Oct4 are
      much more sensitive to etoposide-induced apoptosis than their more differentiated
      progeny. Our study demonstrates that p53 is required for etoposide-induced
      apoptosis of hESC and reveals, at least in part, the molecular mechanism of DNA
      damage-induced apoptosis in hESC.

PMID- 19383393
TI  - Reduction of myocardial infarct size by human mesenchymal stem cell conditioned
      medium.
AB  - Although paracrine effects of mesenchymal stem cells (MSCs) have been suggested
      previously, cardioprotection by human MSC secretions has never been demonstrated.
      Human MSC-conditioned medium (CM) was collected by following a clinically
      compliant protocol. In a porcine model of ischemia and reperfusion injury,
      intravenous and intracoronary MSC-CM treatment significantly reduced myocardial
      nuclear oxidative stress as determined by immunostaining for 8-hydroxy-2'
      deoxyguanosine. In addition, expression levels of phospho-SMAD2 and active
      caspase 3 were diminished following CM treatment, suggesting that TGF-beta
      signaling and apoptosis were reduced. This was associated with a 60% reduction in
      infarct size and marked improvement of systolic and diastolic cardiac performance
      as assessed with echocardiography and pressure volume loops. Fractionation
      studies revealed that only the fraction of the CM containing products >1000 kDa
      (100-220 nm) provided cardioprotection in a mouse model of ischemia and
      reperfusion injury. This indicates that the responsible paracrine factor of human
      MSCs is likely a large complex rather than a single small molecule. These data
      identify human MSC-CM as a promising therapeutic option to reduce myocardial
      infarct size in patients with acute MI and suggest that the use of stem cell
      secretions could extend the applicability of stem cells for therapeutic purposes.

PMID- 19383394
TI  - TGF-beta1 induces efficient differentiation of human cardiomyocyte progenitor
      cells into functional cardiomyocytes in vitro.
AB  - The adult mammalian heart has limited regenerative capacity and was generally
      considered to contain no dividing cells. Recently, however, a resident population
      of progenitor cells has been identified, which could represent a new source of
      cardiomyocytes. Here, we describe the efficient isolation and propagation of
      human cardiomyocyte progenitor cells (hCMPCs) from fetal heart and patient
      biopsies. Establishment of hCMPC cultures was remarkably reproducible, with over
      70% of adult atrial biopsies resulting in robustly expanding cell populations.
      Following the addition of transforming growth factor beta, almost all cells
      differentiated into spontaneously beating myocytes with characteristic cross
      striations. hCMPC-derived cardiomyocytes showed gap-junctional communication and
      action potentials of maturing cardiomyocytes. These are the first cells isolated
      from human heart that proliferate and form functional cardiomyocytes without
      requiring coculture with neonatal myocytes. Their scalability and homogeneity are
      unique and provide an excellent basis for developing physiological,
      pharmacological, and toxicological assays on human heart cells in vitro.

PMID- 19383395
TI  - Cerebellar heterokaryon formation increases with age and after irradiation.
AB  - Hematopoietic cells have been demonstrated to survive in many nonhematopoietic
      tissues after transplantation. Apparent "bone marrow-derived" cerebellar Purkinje
      cells in fact result from fusion events and it has been suggested that fusion may
      be a natural physiological phenomenon to rescue dysfunctioning cells. Here, we
      show that fusion of transplanted bone marrow cells with resident Purkinje cells
      is age-dependent and is strongly enhanced when Purkinje cells are damaged by high
      dose irradiation. In addition, Purkinje heterokaryons occur in increased
      frequencies in the cerebellum of normal, unperturbed, aged mice compared to young
      animals. Our data suggest that age- and/or irradiation-induced dysfunctioning of
      Purkinje cells in the cerebellum is required for cell fusion.

PMID- 19383396
TI  - Stem Cell Research. In this issue.

PMID- 19383397
TI  - Toward a Rosetta stone for the stem cell genome: stochastic gene expression,
      network architecture, and external influences.
AB  - We review literature relating to three types of factors known to influence stem
      cell behavior. These factors are stochastic gene expression, regulatory network
      architecture, and the influence of external signals, such as those emanating from
      the niche. Although these factors are considered separately, their shared
      evolutionary history necessitates integration. Stochastic gene expression
      pervades network components; network architecture controls, modulates, or
      exploits this noise while performing additional computation; and such complexity
      also interplays with factors external to cells. Adequate understanding of each of
      these components, and how they interact, will lead to a conceptual model of the
      stem cell regulatory system that can be used to drive hypothesis-driven research
      and facilitate interpretation of experimental data.

PMID- 19383398
TI  - Proteomics and human embryonic stem cells.
AB  - The derivation of human embryonic stem cells (hESCs) brought cell therapy-based
      regenerative medicine significantly closer to clinical application. However,
      expansion of undifferentiated cells and their directed differentiation in vitro
      have proven difficult to control. This is mainly because of a lack of knowledge
      of the intracellular signaling events that direct these complex processes.
      Additionally, extracellular factors, either secreted by feeder cells that support
      self-renewal and maintain pluripotency or present in serum supplementing
      proprietary culture media, that influence hESC behavior are largely unknown. Xeno
      free media that effectively support long-term hESC self-renewal and
      differentiation to specific types of specialized cells are only slowly becoming
      available. Microarray-based transcriptome analyses have produced valuable gene
      expression profiles of hESCs and indicated changes in transcription that occur
      during differentiation. However, proteins are the actual effectors of these
      events and changes in their levels do not always match changes in their
      corresponding mRNA. Furthermore, information on posttranslational modifications
      that influence the activity of pivotal proteins is still largely missing. Over
      the years, mass spectrometry has experienced major breakthroughs in high
      throughput identification of proteins and posttranslational modifications in
      cells under different conditions. Mass spectrometry-based proteomic techniques
      are being applied with increasing frequency to analyze hESCs, as well as media
      conditioned by feeder cells, and have generated proteome profiles that not only
      support, but also complement, existing microarray data. In this review, the
      various proteomic studies on hESCs and feeder cells are discussed. In a meta
      analysis, comparison of published data sets distinguished 32 intracellular
      proteins and 16 plasma membrane proteins that are present in multiple hESC lines
      but not in differentiated cells, which were therefore likely to include proteins
      important for hESCs. In addition, 13 and 24 proteins, respectively, were commonly
      found in different feeder cell lines of mouse and human origin, some of which may
      be extracellular signaling molecules that play a key role in the undifferentiated
      propagation of hESCs. These findings underscore the power of mass spectrometry
      based techniques to identify novel proteins associated with hESCs by studying
      these cells in an unbiased, discovery-oriented manner on a proteome-wide scale.

PMID- 19383399
TI  - Isolation of major pancreatic cell types and long-term culture-initiating cells
      using novel human surface markers.
AB  - We have developed a novel panel of cell-surface markers for the isolation and
      study of all major cell types of the human pancreas. Hybridomas were selected
      after subtractive immunization of Balb/C mice with intact or dissociated human
      islets and assessed for cell-type specificity and cell-surface reactivity by
      immunohistochemistry and flow cytometry. Antibodies were identified by specific
      binding of surface antigens on islet (panendocrine or alpha-specific) and
      nonislet pancreatic cell subsets (exocrine and duct). These antibodies were used
      individually or in combination to isolate populations of alpha, beta, exocrine,
      or duct cells from primary human pancreas by FACS and to characterize the
      detailed cell composition of human islet preparations. They were also employed to
      show that human islet expansion cultures originated from nonendocrine cells and
      that insulin expression levels could be increased to up to 1% of normal islet
      cells by subpopulation sorting and overexpression of the transcription factors
      Pdx-1 and ngn3, an improvement over previous results with this culture system.
      These methods permit the analysis and isolation of functionally distinct
      pancreatic cell populations with potential for cell therapy.

PMID- 19383400
TI  - Bone marrow cells play only a very minor role in chronic liver regeneration
      induced by a choline-deficient, ethionine-supplemented diet.
AB  - Liver progenitor (oval) cells have enormous potential in the treatment of
      patients with liver disease using a cell therapy approach, but their use is
      limited by their scarcity and the number of donor livers from which they can be
      derived. Bone marrow may be a suitable source. Previously the derivation of oval
      cells from bone marrow was examined in rodents using hepatotoxins and partial
      hepatectomy to create liver damage. These protocols induce oval cell
      proliferation; however, they do not produce the disease conditions that occur in
      humans. In this study we have used the choline-deficient, ethionine-supplemented
      (CDE) diet (which causes fatty liver) and viral hepatitis as models of chronic
      injury to evaluate the contribution of bone marrow cells to oval cells under
      conditions that closely mimic human liver disease pathophysiology. Following
      transplantation of lacZ-transgenic bone marrow cells into congenic mice, liver
      injury was induced and the movement of bone marrow cells to the liver monitored.
      Bone marrow-derived oval cells were observed in response to the CDE diet and
      viral injury but represented a minor fraction (0-1.6%) of the oval cell
      compartment, regardless of injury severity. In all situations only rare,
      individual bone marrow-derived oval cells were observed. We hypothesized that the
      bone marrow cells may replenish oval cells that are expended by protracted liver
      injury and regeneration; however, experiments involving a subsequent episode of
      chronic liver injury failed to induce proliferation of the bone marrow-derived
      oval cells that appeared as a result of the first episode. Bone marrow-derived
      hepatocytes were also observed in all injury models and controls at a frequency
      unrelated to that of oval cells. We conclude that during viral-and steatosis
      induced liver disease the contribution of bone marrow cells to hepatocytes,
      either via oval cells or by independent mechanisms, is minimal and that the
      majority of oval cells responding to this injury are sourced from the liver.

PMID- 19383402
TI  - Identification of a membrane proteomic signature for human embryonic stem cells
      independent of culture conditions.
AB  - Proteomic profiling of human embryonic stem cells (hESC) can identify cell fate
      determination and self-renewal biomarkers. Employing Fourier transform LC-ESI
      MS/MS and MS(3) mass spectrometry, we obtained a membrane proteomic signature
      overlapping between hESC cultured on mouse embryonic fibroblast (MEF) feeders and
      those grown under MEF-free culture conditions. We identified 444 transmembrane or
      membrane-associated proteins, of which 157 were common between both culture
      conditions. Functional annotation revealed CD antigens (10%), adhesion proteins
      (4%), proliferation-associated proteins (4%), receptors (41%), transport proteins
      (21%), structural proteins (5%), and proteins with miscellaneous functions (15%).
      In addition, 15 CD antigens and a number of surface marker molecules not
      previously observed in hESC at a proteome level, e.g., Nodal modulator 1, CD222,
      transgelin-2, and CD81, were identified. In conclusion, we describe the first
      membrane proteome profile of hESC that is independent of culture conditions.
      These data can be used to define the phenotype of hESC.

PMID- 19383401
TI  - The effect of controlled growth factor delivery on embryonic stem cell
      differentiation inside fibrin scaffolds.
AB  - The goal of this project was to develop 3-D biomaterial scaffolds that present
      cues to direct the differentiation of embryonic stem (ES) cell-derived neural
      progenitor cells, seeded inside the scaffolds, into mature neural phenotypes,
      specifically neurons and oligodendrocytes. Release studies were performed to
      determine the appropriate conditions for retention of neurotrophin-3 (NT-3),
      sonic hedgehog, and platelet-derived growth factor (PDGF) by an affinity-based
      delivery system incorporated into fibrin scaffolds. Embryoid bodies containing
      neural progenitors were formed from mouse ES cells, using a 4-/4+ retinoic acid
      treatment protocol, and then seeded inside fibrin scaffolds containing the drug
      delivery system. This delivery system was used to deliver various growth factor
      doses and combinations to the cells seeded inside the scaffolds. Controlled
      delivery of NT-3 and PDGF simultaneously increased the fraction of neural
      progenitors, neurons, and oligodendrocytes while decreasing the fraction of
      astrocytes obtained compared to control cultures seeded inside unmodified fibrin
      scaffolds with no growth factors present in the medium. These results demonstrate
      that such a strategy can be used to generate an engineered tissue for the
      potential treatment of spinal cord injury and could be extended to the study of
      differentiation in other tissues.

PMID- 19383403
TI  - This review explores the various stem and progenitor cell populations that are
      resident in the microvasculature, endothelium, and vessel walls.

PMID- 19383405
TI  - The therapeutic potential of bone marrow-derived mesenchymal stem cells on
      hepatic cirrhosis.
AB  - Hepatic cirrhosis is the end-stage of chronic liver diseases. The majority of
      patients with hepatic cirrhosis die from life-threatening complications occurring
      at their earlier ages. Liver transplantation has been the most effective
      treatment for these patients. Since liver transplantation is critically limited
      by the shortage of available donor livers, searching for an effective alternative
      therapy has attracted great interest in preclinical studies. The transplantation
      of autologous bone marrow-derived mesenchymal stem cells holds great potential
      for treating hepatic cirrhosis. Mesenchymal stem cells can differentiate to
      hepatocytes, stimulate the regeneration of endogenous parenchymal cells, and
      enhance fibrous matrix degradation. Experimental and clinical studies have shown
      promising beneficial effects. This review is intended to translate the bench
      study results to the patients' bedside. The potential interventions of
      mesenchymal stem cells on cirrhosis are illustrated in terms of the cellular and
      molecular mechanisms of hepatic fibrogenesis.

PMID- 19383404
TI  - Resident vascular progenitor cells: an emerging role for non-terminally
      differentiated vessel-resident cells in vascular biology.
AB  - Throughout development and adult life the vasculature exhibits a remarkably
      dynamic capacity for growth and repair. The vasculature also plays a pivotal role
      in the execution of other diverse biologic processes, such as the provisioning of
      early hematopoietic stem cells during embryonic development or the regulation of
      vascular tone and blood pressure. Adding to this importance, from an anatomical
      perspective, the vasculature is clearly an omnipresent organ, with few areas of
      the body that it does not penetrate. Given these impressive characteristics, it
      is perhaps to be expected that the vasculature should require, or at least be
      associated with, a ready supply of stem and progenitor cells. However, somewhat
      surprisingly, it is only now just beginning to be broadly appreciated that the
      vasculature plays host to a range of vessel-resident stem and progenitor cells.
      The possibility that these vessel-resident cells are implicated in processes as
      diverse as tumor vascularization and adaptive vascular remodeling appears likely,
      and several exciting avenues for clinical translation are already under
      investigation. This review explores the various stem and progenitor cell
      populations that are resident in the microvasculature, endothelium, and vessel
      walls and vessel-resident cells capable of phenotypic transformation.

PMID- 19383406
TI  - Stems cells and the price of immortality.

PMID- 19383407
TI  - Derivation of functional insulin-producing cell lines from primary mouse embryo
      culture.
AB  - We have previously described the derivation of insulin-producing cell lines from
      mouse embryonic stem cells (mESCs) by differentiation of an intermediate lineage
      restricted E-RoSH cell line through nutrient depletion in the presence of
      nicotinamide followed by limiting dilution. Here we investigated whether insulin
      producing cell lines could be similarly derived directly from mouse embryo cells
      or tissues. Using a similar approach, we generated the RoSH2.K and MEPI-1 to -14
      insulin-producing cell lines from the 5.5-dpc embryo-derived E-RoSH-analogous
      RoSH2 cell line and a 6.0-dpc mouse embryo culture, respectively. Insulin content
      was approximately 8 microg/10(6) MEPI-1 cells and 0.5 microg/10(6) RoSH2.K cells.
      Like insulin-producing mESC-derived ERoSHK cell lines, both MEPI and RoSH2.K
      lines were amenable to repeated cycles of freeze and thaw, replicated for months
      with a doubling time of 3-4 days, and exhibited genomic, structural, biochemical,
      and pharmacological properties of pancreatic beta-cells, including storage and
      release of insulin and C-peptide in an equimolar ratio. Transplantation of these
      cells also reversed hyperglycemia in streptozotocin-treated SCID mice and did not
      induce teratoma. Like ERoSHK cells, both RoSH2.K and MEPI-1 cells also induced
      hypoglycemia in the mice. Therefore, our protocol is robust and could
      reproducibly generate insulin-producing cell lines from different embryonic cell
      sources.

PMID- 19383408
TI  - Generating mESC-derived insulin-producing cell lines through an intermediate
      lineage-restricted progenitor line.
AB  - Generating surrogate insulin-producing cells from embryonic stem cells (ESCs)
      through in vitro replication of successive steps during pancreatic development
      has been challenging . Here we describe a novel reproducible protocol to
      establish homogeneous and scalable insulin-producing cell lines from mouse (m)
      ESCs via differentiation of the previously described lineage-restricted clonal
      mESC-derived E-RoSH cells. Unlike their parental mESCs, E-RoSH cells expressed
      high levels of mesodermal and endodermal genes. Nutrient depletion in the
      presence of nicotinamide inhibited proliferation of E-RoSH cells and induced
      differentiation into heterogeneous cultures comprising vascular-like structures
      that produced detectable levels of insulin and C-peptide in an equimolar ratio.
      Limiting dilution of these cultures resulted in the isolation of eight
      independent insulin-producing cell lines in five experiments. All these lines
      were cloned and shown to be amenable to repeated cycles of freeze and thaw and to
      replicate for months with a doubling time of 3-4 days. Under such conditions, the
      cultured cells exhibited genomic, structural, biochemical, and pharmacological
      properties of pancreatic beta cells, including storage of an equimolar ratio of
      insulin and C-peptide in granules and release of the contents of these organelles
      through a glucose-sensitive machinery. After transplantation, these cells
      reversed hyperglycemia in streptozotocin-treated SCID mice and did not form
      teratomas.

PMID- 19383409
TI  - Human neural stem cells and astrocytes, but not neurons, suppress an allogeneic
      lymphocyte response.
AB  - Transplantation of human neural stem cells (NSCs) and their derivatives is a
      promising future treatment for neurodegenerative disease and traumatic nervous
      system lesions. An important issue is what kind of immunological reaction the
      cellular transplant and host interaction will result in. Previously, we reported
      that human NSCs, despite expressing MHC class I and class II molecules, do not
      trigger an allogeneic T cell response. Here, the immunocompetence of human NSCs,
      as well as differentiated neural cells, was further studied. Astrocytes expressed
      both MHC class I and class II molecules to a degree equivalent to that of the
      NSCs, whereas neurons expressed only MHC class I molecules. Neither the NSCs nor
      the differentiated cells triggered an allogeneic lymphocyte response. Instead,
      these potential donor NSCs and astrocytes, but not the neurons, exhibited a
      suppressive effect on an allogeneic immune response. The suppressive effect
      mediated by NSCs most likely involves cell-cell interaction. When the
      immunogenicity of human NSCs was tested in an acute spinal cord injury model in
      rodent, a xenogeneic rejection response was triggered. Thus, human NSCs and their
      derived astrocytes do not initiate, but instead suppress, an allogeneic response,
      while they cannot block a graft rejection in a xenogeneic setting.

PMID- 19383410
TI  - Cell division in the cerebral cortex of adult rats after photothrombotic ring
      stroke.
AB  - Neurogenesis has been shown to occur in the cerebral cortex in adult rats after
      ischemic stroke. The origin of the newborn neurons is largely unknown. This study
      aimed to explore cell division in the poststroke penumbral cortex. Adult male
      Wistar rats were subjected to photothrombotic ring stroke. After repeated
      delivery of the DNA duplication marker BrdU, the animals were sacrificed at
      various times poststroke. BrdU was detected by
      immunohistochemistry/immunofluorescence labeling, as was the M-phase marker Phos
      H3 and the spindle components alpha-tubulin/gamma-tubulin. DNA damage was
      examined by TUNEL staining. Cell type was ascertained by double immunolabeling
      with the neuronal markers Map-2ab/beta-tubulin III and NeuN/Hu or the astrocyte
      marker GFAP. From 16h poststroke, BrdU-immunolabeled cells appeared in the
      penumbral cortex. From 24h, Phos H3 was colocalized with BrdU in the nuclei.
      Mitotic spindles immunolabeled by alpha-tubulin/gamma-tubulin appeared inside the
      cortical cells containing BrdU-immunopositive nuclei. Unexpectedly, the markers
      of neuronal differentiation, Map-2ab/beta-tubulin III/NeuN/Hu, were expressed in
      the Phos H3-immunolabeled cells, and NeuN was detected in some cells containing
      spindles. This study suggests that in response to a sublethal ischemic insult,
      endogenous cells with neuronal immunolabeling may duplicate their nuclear DNA and
      commit cell mitosis to generate daughter neurons in the penumbral cortex in adult
      rats.

PMID- 19383411
TI  - Correlation between preimplantation genetic diagnosis for chromosomal
      aneuploidies and the efficiency of establishing human ES cell lines.
AB  - There are several sources from which human embryonic stem cell (hESC) lines can
      be generated: surplus embryos after in vitro fertilization procedures, one- and
      three-pronuclear zygotes, early arrested or highly fragmented embryos that have
      reached the blastocyst stage, or otherwise chromosomally or genetically abnormal
      embryos after preimplantation genetic diagnosis (PGD). We report on the
      efficiency of establishing hESC lines from blastocysts with proven meiotic or
      mitotic errors after sequential testing of both polar bodies and blastomere
      analysis on day 3. The success rate of establishing hESC lines originating from
      blastocysts carrying a meiotic error was as low as 2.4% and differed
      significantly from the success rate of establishing hESC lines originating from
      blastocysts with balanced meiotic errors (21.6%) or mitotic errors (after
      sequential testing (9.1%) and after blastomere testing alone (12.2%)). This
      suggests that it may be reasonable to apply sequential PGD prior to the
      initiation of hESC culture. Information about the karyotype may in the future
      help refine the methods and possibly improve the efficiency by which hESC lines
      are derived from embryos with prezygotic abnormalities. Additionally, it may in
      general prove very difficult to obtain abnormal hESC lines for scientific study
      from aneuploid PGD embryos, which will limit our ability to study the biological
      consequences of chromosomal abnormalities. Furthermore, the success rates for
      generating aneuploid cell lines originating from fertilized oocytes carrying a
      prezygotic nondisjunction error seem to mirror the miscarriage rates during
      pregnancy of embryos carrying such errors.

PMID- 19383413
TI  - ESTOOLS, a project funded by the European Commission(FP6), gathers expertise on
      human embryonic stem cells in 10 countries of the European Research Area.

PMID- 19383414
TI  - Art and human embryonic stem cells: from the bench to the high street.
AB  - ESTOOLS, a project funded by the European Commission (FP6), gathers expertise on
      human embryonic stem cells in 10 countries of the European Research Area. The
      ESTOOLS outreach program uses Art extensively as the only universal cross
      cultural and cross-religion means of communication. The Smile of a Stem Cell
      photo exhibition, a major component of this program, aims to fill a missing link
      between public dissemination of science and science-illiterate citizens.
      Scientists are also engaged to stand at a distance from their work and observe it
      with an outsider's perspective, which enhances their competency to communicate
      science. The photo exhibition, by its situation upstream of scientific education,
      makes itself open to interest and enthusiasm among a public with no prerequired
      scientific knowledge or abilities.

PMID- 19383412
TI  - Enumeration of the colony-forming units-fibroblast from mouse and human bone
      marrow in normal and pathological conditions.
AB  - Bone marrow stromal cell populations, containing a subset of multipotential
      skeletal stem cells, are increasingly contemplated for use in tissue engineering
      and stem cell therapy, whereas their involvement in the pathogenetic mechanisms
      of skeletal disorders is far less recognized. We compared the concentrations of
      stromal clonogenic cells, colony forming units-fibroblast (CFU-Fs), in norm and
      pathology. Initially, culture conditions were optimized by demonstrating that
      fetal bovine serum heat inactivation could significantly repress colony
      formation. Using non-heat-inactivated fetal bovine serum, the concentration of
      CFU-Fs (colony-forming efficiency, CFE) ranged from 3.5 +/- 1.0 to 11.5 +/- 4.0
      per 1 x 10(5) nucleated cells in five inbred mouse strains. In four transgenic
      lines with profound bone involvement, CFE was either significantly reduced or
      increased compared to wild-type littermates. In normal human donors, CFE
      decreased slightly with age and averaged 52.2 +/- 4.1 for children and 32.3 +/-
      3.0 for adults. CFE was significantly altered in patients with several skeletal,
      metabolic, and hematological disorders: reduced in congenital generalized
      lipodystrophy, achondroplasia (SADDAN), pseudoachondroplasia, and Paget disease
      of bone and elevated in alcaptonuria and sickle cell anemia. Our findings
      indicate that under appropriate culture conditions, CFE values may provide useful
      insights into bone/bone marrow pathophysiology.

PMID- 19383415
TI  - The changing landscape of European and international regulation on embryonic stem
      cell research.
AB  - Legislation in individual member states of the European Union on human embryonic
      stem cell (hESC) research is as divergent as the different cultural, ethical, and
      religious views on the issue. On the occasion of the public launch of the
      European Human Embryonic Stem Cell Registry (hESCreg: www.hescreg.eu), a two-day
      symposium was held on 18 and 19 January 2008 in Berlin to offer participants an
      overview of state-of-the-art hESC research and legislation throughout Europe and
      in selected regions of the world. Thirty leading scientists from Europe as well
      as from the United States, Japan, and Australia reported on a range of aspects
      related to research on hESC and reviewed the key elements of the newly
      established hESCreg database of hESC lines. In this article we summarize and
      complete the information on the current status of international hESC regulation.

PMID- 19383416
TI  - A new in vitro model for stem cell differentiation and interaction.
AB  - Development involves an interplay between various cell types from their birth to
      their disappearance by differentiation, migration, or death. Analyzing these
      interactions provides insights into their roles during the formation of a new
      organism. As a study tool for these interactions, we have created a model based
      on embryoid bodies (EBs) generated from mouse embryonic stem (mES) cells, which
      can be used to visualize the differentiation of mES cells into specific cell
      types while at the same time allowing controlled removal of this same cell
      population using an enzyme-prodrug approach. Cell-specific expression of Cre
      induces a switch of EGFP expression to LacZ. Furthermore, it leads to the
      expression of nitroreductase (NTR), which in combination with the prodrug CB1954
      induces apoptosis. Here, we validate this model by showing expression of LacZ and
      NTR after Cre-mediated recombination. Additionally we show, as an example, that
      we can target the endothelial cells in EBs using the Tie-2 promoter driving Cre.
      Ablating Cre-expressing cells by adding CB1954 to the culture led to an abrogated
      vascular formation. This system can easily be adapted to determine the fate and
      interaction of many different cell types provided that there is a cell-type
      specific promoter available.

PMID- 19383417
TI  - CD marker expression profiles of human embryonic stem cells and their neural
      derivatives, determined using flow-cytometric analysis, reveal a novel CD marker
      for exclusion of pluripotent stem cells.
AB  - Human embryonic stem cells (hESCs) are pluripotent cells that can differentiate
      into neural cell lineages. These neural populations are usually heterogeneous and
      can contain undifferentiated pluripotent cells that are capable of producing
      teratomas in cell grafts. The characterization of surface protein profiles of
      hESCs and their neural derivatives is important to determine the specific markers
      that can be used to exclude undifferentiated cells from neural populations. In
      this study, we analyzed the cluster of differentiation (CD) marker expression
      profiles of seven undifferentiated hESC lines using flow-cytometric analysis and
      compared their profiles to those of neural derivatives. Stem cell and progenitor
      marker CD133 and epithelial adhesion molecule marker CD326 were more highly
      expressed in undifferentiated hESCs, whereas neural marker CD56 (NCAM) and neural
      precursor marker (chemokine receptor) CD184 were more highly expressed in hESC
      derived neural cells. CD326 expression levels were consistently higher in all
      nondifferentiated hESC lines than in neural cell derivatives. In addition, CD326
      positive hESCs produced teratomas in SCID mouse testes, whereas CD362-negative
      neural populations did not. Thus, CD326 may be useful as a novel marker of
      undifferentiated hESCs to exclude undifferentiated hESCs from differentiated
      neural cell populations prior to transplantation.

PMID- 19383418
TI  - Generation of tissue-specific cells from MSC does not require fusion or donor-to
      host mitochondrial/membrane transfer.
AB  - Human mesenchymal stem cells (MSC) hold great promise for cellular replacement
      therapies. Despite their contributing to phenotypically distinct cells in
      multiple tissues, controversy remains regarding whether the phenotype switch
      results from a true differentiation process. Here, we studied the events
      occurring during the first 120 h after human MSC transplantation into a large
      animal model. We demonstrate that MSC, shortly after engrafting different
      tissues, undergo proliferation and rapidly initiate the differentiative process,
      changing their phenotype into tissue-specific cells. Thus, the final level of
      tissue-specific cell contribution is not determined solely by the initial level
      of engraftment of the MSC within that organ, but rather by the proliferative
      capability of the ensuing tissue-specific cells into which the MSC rapidly
      differentiate. Furthermore, we show that true differentiation, and not cell
      fusion or transfer of mitochondria or membrane-derived vesicles between
      transplanted and resident cells, is the primary mechanism contributing to the
      change of phenotype of MSC upon transplantation.

PMID- 19383419
TI  - Generation of functional neurons and glia from multipotent adult mouse germ-line
      stem cells.
AB  - Recently, we reported the successful establishment of multipotent adult germ-line
      stem cells (maGSCs) from cultured adult mouse spermatogonial stem cells. Similar
      to embryonic stem cells, maGSCs are able to self-renew and differentiate into
      derivatives of all three germ layers. These properties make maGSCs a potential
      cell source for the treatment of neural degenerative diseases. In this study, we
      describe the generation of maGSC-derived proliferating neural precursor cells
      using growth factor-mediated neural lineage induction. The neural precursors were
      positive for nestin and Sox1 and could be continuously expanded. Upon further
      differentiation, they formed functional neurons and glial cells, as demonstrated
      by expression of lineage-restricted genes and proteins and by
      electrophysiological properties. Characterization of maGSC-derived neurons
      revealed the generation of specific subtypes, including GABAergic, glutamatergic,
      serotonergic, and dopaminergic neurons. Electrophysiological analysis revealed
      passive and active membrane properties and postsynaptic currents, indicating
      their functional maturation. Functional networks formed at later stages of
      differentiation, as evidenced by synaptic transmission of spontaneous neuronal
      activity. In conclusion, our data demonstrate that maGSCs may be used as a new
      stem cell source for basic research and biomedical applications.

PMID- 19383420
TI  - Micropatterning of human embryonic stem cells dissects the mesoderm and endoderm
      lineages.
AB  - Human pluripotent cells such as human embryonic stem cells (hESC) are a great
      potential source of cells for cell-based therapies; however, directing their
      differentiation into the desired cell types with high purity remains a challenge.
      The stem cell microenvironment plays a vital role in directing hESC fate and we
      have previously shown that manipulation of colony size in a serum- and cytokine
      free environment controls self-renewal and differentiation toward the
      extraembryonic endoderm lineage. Here we show that, in the presence of bone
      morphogenetic protein 2 and activin A, control of colony size using a
      microcontact printing technology is able to direct hESC fate to either the
      mesoderm or the endoderm lineage. Large, 1200-mum-diameter colonies give rise to
      mesoderm, while small 200-mum colonies give rise to definitive endoderm. This
      study links, for the first time, cellular organization to pluripotent cell
      differentiation along the mesoderm and endoderm lineages.

PMID- 19383421
TI  - Complete screening for glucocerebrosidase mutations in Parkinson disease patients
      from Greece.
AB  - Mutations in beta-glucocerebrosidase gene (GBA) have been implicated in Parkinson
      disease (PD). A Greek cohort of 172 PD patients and 132 control individuals were
      screened for GBA mutations by complete sequencing of the gene's exons. Four
      mutations previously associated with Gaucher disease and/or Parkinson's disease
      (L445P, D409H, E326K, H255Q) were detected, as well as five newly identified
      variants (R329H, L268L, S271G, T428K, V460L), providing for the first time data
      regarding the frequency of GBA mutations among PD patients and controls, in the
      Greek population. H255Q was the most common GBA mutation among Greek PD patients
      (4/172). V460L was only found in control individuals (2/132). Overall, GBA
      mutations were significantly overrepresented in a subgroup of early onset PD
      patients, compared to controls (P = 0.019, OR = 4.2; 95%CI = 1.28 -- 13.82),
      suggesting that GBA mutations may modify age of onset for PD.

PMID- 19383422
TI  - Decreased immobility in swimming test by homologous interferon-alpha in mice
      accompanied with increased cerebral tryptophan level and serotonin turnover.
AB  - Animal models are used to decipher the pathophysiology of IFN-alpha-induced
      psychiatric complications in humans. However, the behavioral effects of IFN-alpha
      in rodents remain highly controversial. In contrast to homologous IFN-alpha, our
      recent study revealed that human IFN-alpha, which was used in many previous
      investigations, had no biological activity in mice. To evaluate the behavioral
      effects of homologous IFN-alpha in mice, adult C57BL/6J mice were treated with
      carrier-free murine IFN-alpha and tested on a number of behavioral paradigms.
      Surprisingly, contrary to previous reports, IFN-alpha treatment decreased the
      time spent immobile in the forced-swimming test after a single intraperitoneal
      injection at 2 x 10(6)IU/kg, whereas general locomotor activity was not altered.
      The elevated plus-maze (EPM) test showed a trend toward an increased anxiety
      profile in IFN-alpha-treated mice. The tail-suspension and light dark exploration
      test revealed no difference between IFN-alpha-treated and control animals.
      Interestingly, neurochemical analysis revealed significantly increased
      concentrations of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA)/serotonin (5
      HT) ratios following IFN-alpha treatment in selected brain regions. Thus,
      systemic murine IFN-alpha treatment increases swimming time in mice. Increased
      cerebral serotonin turnover as well as increased tryptophan concentrations,
      induced by IFN-alpha, implicates serotonergic neurotransmission in behavioral
      dysfunction caused by this innate immune mediator.

PMID- 19383423
TI  - Inverse relation between intensity of GFAP expression in the substantia
      gelatinosa and degree of chronic mechanical allodynia.
AB  - Glial cells are known to have a large impact on neuropathic pain conditions.
      Within the spinal cord, microglia rapidly respond to peripheral nerve injury,
      resulting in central sensitization and ultimately in the onset of enhanced pain
      behaviour. Astroglia respond with a short delay and are thought to contribute to
      the early maintenance of neuropathic pain. Nevertheless, it is unknown whether
      the roles of these glial cell types can be influenced by the chronicity of the
      neuropathology. Here, the persistent responses of astroglia and microglia to
      peripheral nerve injury within central pain networks in the upper dorsal horn
      laminae were studied. At 12 weeks after complete sciatic nerve injury,
      upregulation of glial fibrillary acidic protein (GFAP), but not complement
      receptor-3, could be detected in laminae II and III. Moreover, it was found that
      neuropathic animals with a higher degree of mechanical allodynia had a lower
      intensity of GFAP expression in lamina II (substantia gelatinosa). From these
      data we conclude that the role of astroglial responses in mechanical allodynia
      after peripheral nerve injury may be less straightforward as previously thought.
      Although astroglia are known to play a pro-nociceptive role in early neuropathic
      pain states, this role may shift to anti-nociception in more chronic pain states.

PMID- 19383424
TI  - Brain-derived neurotrophic factor serum levels before and after treatment for
      acute mania.
AB  - Accumulating evidence suggests that reduced levels of brain-derived neurotrophic
      factor (BDNF) in acute mood episodes may play an important role in the
      pathophysiology of bipolar disorder (BD). In order to assess changes in BDNF
      serum levels in BD patients before and after treatment for acute mania, ten
      bipolar patients were prospectively examined at inpatient unit admission and
      discharge. Diagnoses were made using the Structured Clinical Interview for DSM
      IV, SCID-I. Serum BDNF levels were measured by sandwich ELISA. The results showed
      that BDNF levels were decreased in BD patients during mania when compared to
      controls (p=0.013) but this difference was no longer significant after treatment
      (p=0.126). A sharp increase in BDNF levels was found after treatment of the
      episode of acute mania (p=0.010). These findings suggest that the changes in BDNF
      serum levels may be associated with treatment response in acute mania. Further
      studies designed to validate the use of BDNF as a marker of treatment response in
      bipolar disorder are warranted.

PMID- 19383425
TI  - Evidence that transduction of electromagnetic field is mediated by a force
      receptor.
AB  - Low-strength magnetic fields triggered onset and offset evoked potentials,
      indicating that the detection process was a form of sensory transduction; whether
      the field interacted directly with an ion channel or indirectly via a signaling
      cascade is unknown. By analogy with electrosensory transduction in lower life
      forms, we hypothesized that the evoked potentials were initiated by a force
      exerted by the induced electric field on an ion channel in the plasma membrane.
      We applied a rapid magnetic stimulus (0.2 ms) and found that it produced evoked
      potentials indistinguishable in latency, magnitude, and frequency from those
      found previously when the stimulus was 50 times slower. The ability of the field
      detection system in human subjects to respond to the rapid stimulus supported the
      theory that the receptor potentials necessary for production of evoked potentials
      originated from a direct interaction between the field and an ion channel in the
      plasma membrane that resulted in a change in the average probability of the
      channel to be in the open state.

PMID- 19383427
TI  - Effects of postural threat on walking features of Parkinson's disease patients.
AB  - This study investigated whether or not gait kinematics among healthy older
      individuals and Parkinson's disease (PD) patients are influenced by postural
      threat. Eight healthy older individuals and eight PD patients were examined while
      walking at self-selected velocities, under three conditions of postural threat:
      unconstrained floor; constrained floor (19cm wide); constrained and elevated
      floor (19cm wide by 10cm high). Independent of the surface conditions, due to
      motor disturbances caused by the PD these patients walked slower, with shorter
      strides, and spent more time in the double support phase and less time in the
      swing phase than did their matched controls. Increases in postural threat
      resulted in altered gait kinematics for all subjects. Specifically, stride
      length, stride velocity, cadence, and heel contact velocity decreased, and stride
      duration and double support duration increased relative to increases in postural
      threat. All gait alterations were the result of participants' attempts to
      facilitate locomotion control and maintain stability. The results of this study
      reveal that width and height constraints effectively perturbed the balance of all
      of the walking older individuals. The PD patients were able to modulate gait
      parameters when faced by a postural threat task.

PMID- 19383426
TI  - H-reflex down-conditioning greatly increases the number of identifiable GABAergic
      interneurons in rat ventral horn.
AB  - H-reflex down-conditioning increases GABAergic terminals on spinal cord
      motoneurons. To explore the origins of these terminals, we studied the numbers
      and distributions of spinal cord GABAergic interneurons. The number of
      identifiable GABAergic interneurons in the ventral horn was 78% greater in rats
      in which down-conditioning was successful than in naive rats or rats in which
      down-conditioning failed. No increase occurred in other spinal lamina or on the
      contralateral side. This finding supports the hypothesis that the corticospinal
      tract influence that induces the motoneuron plasticity underlying down
      conditioning reaches the motoneuron through GABAergic interneurons in the ventral
      horn.

PMID- 19383428
TI  - (-)Epigallocatechin-3-gallate inhibits the spontaneous firing of rat locus
      coeruleus neuron.
AB  - (-)Epigallocatechin-3-gallate (EGCG), a tea catechin, has been known to cause
      many biological actions, such as anxiolytic and hypotensive effects in behavioral
      studies. However, to date, few reports investigate its neuronal modulation. In
      this study, intracellular recording was used to test the neuronal modulation of
      different catechins on locus coeruleus (LC) neuron, which has been demonstrated
      to be affected by cardiovascular function regulation and stressful events.
      Several catechins (1 -- 1,000 microM) were tested, including: (-)catechin (C), (
      )catechingallate (CG), (-)epicatechin (EC), (-)epicatechin-3-gallate (ECG),
      (?)epigallocatechin (EGC) and EGCG. The results showed that catechins EC, ECG,
      EGC and EGCG could inhibit the spontaneous firing of the LC neurons; furthermore,
      these catechins show potency and efficacy in the order of EGCG>ECG>EC
      approximately EGC. Among the tested catechins, EGCG was the most potent in
      inhibiting LC's spontaneous firing with IC(50) of 20.5 microM. This caused us to
      further examine the EGCG's desensitization and tolerance properties. When
      continuously administering EGCG at 1 -- 300 microM for 20 min, no acute
      desensitization appeared. However, repeated applications of 300 microM EGCG at 5
      min each time showed different results. The second and third applications induced
      less responses compared to that of the first application, suggesting a
      development of tolerance towards EGCG in inhibiting LC neuronal activity. Our
      data suggest that EGCG can inhibit LC neuron's spontaneous firing in a dose
      dependent manner, with developed tolerance only when high concentration of EGCG
      is repeatedly applied.

PMID- 19383430
TI  - Chronic stroke and aging: the impact of acoustic stimulus intensity on
      fractionated reaction time.
AB  - In control samples, intense acoustic "go" stimuli accelerate the central and
      peripheral motor processes that compose simple reaction time movements. The goal
      of the current study was to determine whether movements that are initiated to
      intense acoustic cues facilitate simple reaction times in (1) adults with chronic
      stroke as compared to age matched controls and (2) in older as compared to
      younger adults. EMG and force data were collected from three groups (stroke,
      older adults, and younger adults) during a ballistic wrist and finger extension
      task. Movements were made to the onset of 80 dB and 107 dB acoustic cues and
      simple reaction times were fractionated into premotor and motor components. The
      present findings offer two important contributions to the literature. First,
      increases in stimulus intensity led to faster motor times in the impaired limb of
      stroke subjects. Second, increased stimulus intensity led to faster premotor
      reaction times across all groups, although an age rather than a stroke-specific
      motor deficit was evidenced, with the younger control group displaying
      significantly faster premotor times. Findings are integrated with previous
      evidence concerning post stroke corticospinal tract integrity and are interpreted
      via mechanisms which address stroke and age-related changes in motoneurons and
      activity in motor units.

PMID- 19383431
TI  - Cilostazol protects against hemorrhagic transformation in mice transient focal
      cerebral ischemia-induced brain damage.
AB  - Cilostazol, an antiplatelet drug used to treat intermittent claudication, has
      been reported to offer neuroprotection and endothelial protection in animals with
      ischemic brain injury. Here, we evaluated the protection afforded by cilostazol
      against ischemic brain injury and hemorrhagic transformation. Mice subjected to a
      2-h filamental middle cerebral artery (MCA) occlusion were treated with
      cilostazol (10mg/kg, intraperitoneally just after the occlusion) or with vehicle.
      Histological outcomes (infarct volume and hemorrhagic transformation) and Evans
      blue extravasation were assessed after reperfusion. Mean infarct volume,
      hemorrhagic transformation, and Evans blue extravasation were all significantly
      reduced in the cilostazol-treated group. Thus, cilostazol protected against
      ischemic brain injury and hemorrhagic transformation in mice subjected to
      transient focal cerebral ischemia.

PMID- 19383429
TI  - Messenger RNA for neuropeptide Y in the arcuate nucleus increases in parallel
      with plasma adrenocorticotropin during sepsis in the rat.
AB  - Loss of appetite occurs in the cecal ligation and puncture (CLP) model of sepsis
      in conjunction with the activation of central neural stress pathways.
      Neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus is upregulated by
      several stressors and is stimulatory to feeding. To examine the response of NPY
      messenger RNA in the arcuate nucleus to sepsis, we used biotinylated RNA probes
      and a quantitative non-isotopic in situ hybridization approach in cryo-preserved
      sections from rats made septic by CLP. The mRNA in arcuate neurons was
      upregulated from the first day after CLP. By the afternoon of the third day
      through the morning of the fourth day, the average grey level of NPY mRNA
      clusters was 30% greater after CLP than after sham surgery (P<0.05), and the
      integrated optical density based on both the grey level and the amount of area
      with detectable mRNA was 60% greater after CLP than after sham surgery (P<0.03).
      Both the average grey level and area with detectable staining were positively
      correlated to plasma ACTH (r=0.953 and 0.917, respectively, n=10 and P<0.01 in
      each case). Thus sepsis increases the expression of the mRNA for NPY in the
      arcuate nucleus in proportion to the magnitude of the stress response. However,
      the suppression of feeding behavior in the CLP model suggests that sepsis
      activates additional mechanisms that negate the orexigenic contribution of the
      neuronal increase in NPY mRNA.

PMID- 19383432
TI  - Hippocampal heterogeneity in spatial memory revealed by cytochrome oxidase.
AB  - The oxidative metabolism was assessed in the septal, intermediate and temporal
      hippocampus in Wistar rats that were trained following a working memory schedule
      in the Morris water maze. The cytochrome oxidase histochemistry was measured at
      90 min, 6, 24 and 48 h post-training. We found an increase in the septal dentate
      gyrus at 90 min, at 6h the increase was also found in CA3 and CA1 regions and
      returned to basal levels at 24h. In contrast, the intermediate region showed
      lower increase, limited to the dentate gyrus and CA3 at 24h post-training. No
      changes were found in the temporal hippocampus. These findings suggest that
      septal and intermediate hippocampal zones participate in this spatial learning
      and contribute at different moments to process this information.

PMID- 19383434
TI  - Numbers are represented in egocentric space: effects of numerical cues and
      spatial reference frames on hand laterality judgements.
AB  - Convergent findings demonstrate that numbers can be represented according to a
      spatially oriented mental number line. However, it is not established whether a
      default organization of the mental number line exists (i.e., a left-to-right
      orientation) or whether its spatial arrangement is only the epiphenomenon of
      specific task requirements. To address this issue we performed two experiments in
      which subjects were required to judge laterality of hand stimuli preceded by
      small, medium or large numerical cues; hand stimuli were compatible with
      egocentric or allocentric perspectives. We found evidence of a left-to-right
      number -- hand association in processing stimuli compatible with an egocentric
      perspective, whereas the reverse mapping was found with hands compatible with an
      allocentric perspective. These findings demonstrate that the basic left-to-right
      arrangement of the mental number line is defined with respect to the body-centred
      egocentric reference frame.

PMID- 19383433
TI  - Involvement of PGE2 and PGDH but not COX-2 in thrombin-induced cortical neuron
      apoptosis.
AB  - The pathways that contribute to thrombin-induced neuron death have been
      incompletely defined. Induction of cyclooxygenase 2 (COX-2), the enzyme that
      catalyzes the first step in prostaglandin synthesis, promotes neuronal injury.
      PGE2, a downstream product of COX-2 metabolism, is neurotoxic in vitro and in
      vivo, and is thought to be the bioactive mediator responsible for COX-2
      neurotoxicity. The objective of this study is to determine the ability of
      thrombin to affect PGE2 metabolism in cultured neurons. The data show that in
      thrombin-induced apoptosis of cultured neurons, PGE2 release increases when COX-2
      is absent, and is regulated by prostaglandin dehydrogenase (PGDH), a key enzyme
      that degrades PGE2. NS398, a COX-2 specific inhibitor, protects neurons against
      thrombin toxicity, by inducing active PGDH. These data implicate PGDH in thrombin
      mediated neuronal cell death.

PMID- 19383435
TI  - Occlusal disharmony increases stress response in rats.
AB  - Repeated or chronic stress is known to produce structural and functional changes
      in the rat brain, and in particular, alter the response of the hypothalamic --
      pituitary -- adrenal (HPA) axis to subsequent new stress. Occlusal disharmony via
      placement of acryl cap on the lower incisors of rats is perceived as chronic
      stress. To determine the response of the HPA axis to subsequent new stress in
      rats with occlusal disharmony, we measured plasma corticosterone levels in these
      rats after subjecting them to new stress. Plasma corticosterone levels in rats
      with and without incisal cap increased and reached a peak 30 min after exposure
      to the new stress. However, a later decrease in plasma corticosterone levels from
      peak levels was found in rats with incisal cap compared with rats without incisal
      cap. This finding suggests that occlusal disharmony alters the response of the
      HPA axis to subsequent new stress.

PMID- 19383436
TI  - Season of birth and personality in healthy young adults.
AB  - The purpose of this study was to explore a possible season of birth effect on big
      five personality traits, taking into account also gender and circadian typology
      variables. A sample of 419 healthy young adults (249 females and 170 males) was
      administered the self-report version of the Big Five Observer (BFO) and the
      Morningness -- Eveningness Questionnaire (MEQ) to determine, respectively,
      personality features and circadian preference. Participants were subdivided into
      four season groups, according to their birth date. No significant season of birth
      effect was observed as regards personality traits even if summer-born
      participants tended to score lower on the conscientiousness dimension. In regard
      to the conscientiousness domain, there was a significant interaction between
      gender and season of birth. Males presented greater conscientiousness variation
      with summer born participants scoring lower. On the basis of a multiple
      regression analysis, MEQ score proved to be a better predictor of
      conscientiousness than gender, age, and season of birth. The results provide no
      clear evidence for a season of birth effect on the big five personality traits.
      It is possible that circadian preference may modulate the season of birth effect
      on personality traits.

PMID- 19383437
TI  - Event-related potentials during the evaluation of the appropriateness of
      cooperative actions.
AB  - Event-related potentials (ERPs) were recorded during the evaluation of the
      appropriateness of cooperative actions between two people. We used pictures of
      pass-and-receive actions as one type of cooperative actions, in which one person
      passed an object and another reached out to receive it with a preshaped hand.
      Eleven participants judged whether the receiving actions were appropriate or
      inappropriate in relation to the passing ones. The inappropriate actions elicited
      a widely distributed and parietal maximum N400 as compared with the appropriate
      ones. These results suggest that the N400 is evoked in the incongruous context in
      which two people perform inappropriate cooperative actions and is related to the
      semantic processing that involves the prediction of interpersonal action
      sequences.

PMID- 19383438
TI  - A cerebral functional imaging study by positron emission tomography in healthy
      volunteers receiving true or sham acupuncture needling.
AB  - Our recent studies have demonstrated that needling in Baihui, Shuigou and Shenmen
      enhances glucose metabolism in the frontal lobes, thalamus, temporal lobe, and
      the lentiform nucleus in vascular dementia. This study examined the effect of
      true, sham and overt needling in Waiguan (TE5) on cerebral changes by positron
      emission tomography (PET) technique. Eighteen healthy volunteers were randomized
      to receive overt control, true or sham needling therapy. To manipulate true
      needling, a needle was inserted into 15+/-2mm into Waiguan and "deqi" was
      achieved by proper needle manipulation. For sham needling, needles with a blunt
      tip were pushed against the skin as the shaft moved into the handle, giving an
      illusion of insertion. For overt placebo, blunt needles were used and subjects
      did not receive any needling penetration. The tracer used was (18)fluoride
      deoxygluocse. PET images obtained were processed and analyzed by the SPM2
      software. Compared with overt needling, brain areas BA7, 13, 18, 19, 21, 22, 27,
      38, 40, 42 and 45 in Waiguan true needling group were significantly activated and
      areas BA4, 6, 7, 19, 22 and 41 in sham needling group showed obvious activation.
      Compared to sham needling group, marked activation points were found in the areas
      of BA13 and 42 and left cerebellum in true needling group. Our study revealed a
      marked difference in brain metabolic changes between true and sham needling in
      Waiguan. Further studies are needed to explore the cerebral changes in patients
      with acupuncture and the pathological implications.

PMID- 19383439
TI  - Modulation of P2X receptors in dorsal root ganglion neurons of streptozotocin
      induced diabetic neuropathy.
AB  - Painful diabetic neuropathy causes hyperalgesia and does not respond to commonly
      used analgesics such as non-steroidal anti-inflammatory drugs or opioids at doses
      below those producing disruptive side effects. In the present study, we examined
      the effect of P2X receptor antagonists, which are known to modulate the pain
      pathway, on mechanical hyperalgesia in streptozotocin (STZ)-induced diabetic
      mice. The paw withdrawal frequency measured by von Frey filaments, began to
      significantly increase 5 days after STZ injection and was maintained for more
      than 14 days. Intrathecal administration of P2X receptor antagonists (PPADS and
      TNP-ATP) inhibited the mechanical allodynia in diabetic mice. The levels of
      P2X(2) and P2X(3) receptors mRNA were significantly increased in diabetic mice at
      14 days after the intravenous injection of STZ. These results suggest that the
      upregulation of P2X(2), P2X(3) and/or P2X(2/3) receptor in DRG neurons is
      associated with mechanical allodynia in STZ-induced diabetic mice.

PMID- 19383440
TI  - Post-acute pathological changes in the thalamus and internal capsule in aged mice
      following controlled cortical impact injury: a magnetic resonance imaging, iron
      histochemical, and glial immunohistochemical study.
AB  - Traumatic brain injury (TBI) is a major cause of neurological disability across
      all ages, but the elderly are particularly vulnerable and have a worse prognosis
      than younger individuals. To advance the understanding of long-term pathogenesis
      induced by TBI in the elderly, aged mice (21 -- 24 months) were given a
      controlled cortical impact (CCI) injury to the sensorimotor cortex, and their
      brains were analyzed by MRI and histopathology at 1 and 2 months after CCI
      injury, a post-acute period. A T2 hypointensity was observed in the ipsilateral
      thalamus but not in the contralateral thalamus or in the thalamus of sham
      operated, control mice. The hypointensity was co-localized with increased
      histochemical staining of iron, a paramagnetic substance that causes a shortening
      of the T2 relaxation time. Since iron catalyzes reactions that lead to toxic free
      radicals, the deposition of iron in the thalamus raises the possibility that it
      promotes pathogenesis following TBI. Astrocyte gliosis and microgliosis were also
      observed in the ipsilateral thalamus in the post-acute period. The ipsilateral
      internal capsule displayed a trend for a T2 hypointensity, however, unlike the
      thalamus it did not have an increase of iron or GFAP staining, but it did have
      evidence of microgliosis. In summary, areas of T2 hypointensity were revealed in
      both the thalamus and internal capsule during the post-acute period following CCI
      injury, but the underlying pathology appeared to be distinct between these
      regions.

PMID- 19383441
TI  - Fatiguing exercise attenuates pain-induced corticomotor excitability.
AB  - The purpose of this study was to assess net corticomotor excitability during a
      painful stimulus before and after exercise. In the first study, 25 subjects
      participated in three sessions: one familiarization session and two experimental
      sessions. The two experimental sessions were randomized and involved measurement
      of pain perception before and after (1) a submaximal isometric fatiguing
      contraction with the left elbow flexor muscles and (2) 30 min of quiet rest. Pain
      perception was assessed using a pressure device applied to the right index finger
      for 2 min. Motor evoked potentials (MEPs) of the left brachioradialis muscle were
      measured following transcranial magnetic stimulation (TMS) which was delivered
      before, during, and after the 2 min pain test. In the second study, 12 subjects
      participated in one session which involved application of TMS to elicit MEPs at
      the same time points as in study one, before and after a submaximal fatiguing
      contraction, but in the absence of pain. In the absence of the mechanical noxious
      stimulus, MEP amplitude was reduced following the fatiguing contraction and
      unchanged over this time period. In study one, pain threshold increased and pain
      ratings decreased following the isometric contraction but not after 30 min of
      quiet rest. During application of the mechanical noxious stimulus to the right
      index finger, MEP amplitude of the left brachioradialis muscle increased
      indicating an increase in net corticomotor excitability. The pain-induced
      increase in MEPs was attenuated following the isometric fatiguing contraction and
      this occurred in parallel with the decrease in pain.

PMID- 19383442
TI  - CSF proteome analysis in clinically isolated syndrome (CIS): candidate markers
      for conversion to definite multiple sclerosis.
AB  - Cerebrospinal fluid (CSF) is a promising source of biomarkers in clinically
      isolated syndrome (CIS), which frequently presents as a first episode of multiple
      sclerosis (MS). Using the two-dimensional difference in gel electrophoresis (2-D
      DIGE), we compared CSF samples from patients with CIS that remained CIS (CIS-CIS,
      n=8) over a follow-up time of 2 years and from patients with CIS that developed
      definite MS of the relapsing-remitting subtype (CIS-RRMS, n=8) over the same
      period. Protein spots that showed significant differences between patients and
      controls were selected for further analysis by MALDI-TOF mass spectrometry. For
      validation of identified spots ELISA experiments were performed. We identified
      one protein that was upregulated in CIS-RRMS (serin peptidase inhibitor) and
      eight proteins (alpha-1-B-glycoprotein, Fetuin-A, apolipoprotein A4, haptoglobin,
      human Zinc-alpha-2-glycoprotein (ZAG), Retinol-binding protein, superoxid
      dismutase 1, transferrin) that were down-regulated in CIS-RRMS vs. CIS-CIS. For
      Fetuin-A, our findings could be confirmed by ELISA. The pathophysiological role
      as well as clinical relevance of these candidate proteins in CIS remains to be
      further clarified by future studies.

PMID- 19383443
TI  - Morphology of Caulobacter crescentus and the Mechanical Role of Crescentin.
AB  - Bacterial cells exist in a wide variety of shapes. To understand the mechanism of
      bacterial shape maintenance, we investigate the morphology of Caulobacter
      crescentus, which is a Gram-negative bacterium that adopts a helical crescent
      shape. It is known that crescentin, an intermediate filament homolog of C.
      crescentus, is required for maintaining this asymmetrical cell shape. We employ a
      continuum model to understand the interaction between the bacterial cell wall and
      the crescentin bundle. The model allows us to examine different scenarios of
      attaching crescentin to the cell wall and compute the shape of the bacterium.
      Results show that if the sole influence of crescentin is mechanical, then the
      crescentin bundle is unrealistically rigid and must be attached to the cell wall
      directly. The model suggests that alternative roles for crescentin such as how it
      influences cell wall growth must be considered.

PMID- 19383444
TI  - Tracking of single quantum dot labeled EcoRV sliding along DNA manipulated by
      double optical tweezers.
AB  - Fluorescence microscopy provides a powerful method to directly observe single
      enzymes moving along a DNA held in an extended conformation. In this work, we
      present results from single EcoRV enzymes labeled with quantum dots which
      interact with DNA manipulated by double optical tweezers. The application of
      quantum dots facilitated accurate enzyme tracking without photobleaching whereas
      the tweezers allowed us to precisely control the DNA extension. The labeling did
      not affect the biochemical activity of EcoRV checked by directly observing DNA
      digestion on the single molecule level. We used this system to demonstrate that
      during sliding, the enzyme stays in close contact with the DNA. Additionally,
      slight overstretching of the DNA resulted in a significant decrease of the 1D
      diffusion constant, which suggests that the deformation changes the energy
      landscape of the sliding interaction. Together with the simplicity of the setup,
      these results demonstrate that the combination of optical tweezers with
      fluorescence tracking is a powerful tool for the study of enzyme translocation
      along DNA.

PMID- 19383445
TI  - The Fip35 WW domain folds with structural and mechanistic heterogeneity in
      molecular dynamics simulations.
AB  - We describe molecular dynamics simulations resulting in the folding the Fip35
      Hpin1 WW domain. The simulations were run on a distributed set of graphics
      processors, which are capable of providing up to two orders of magnitude faster
      computation than conventional processors. Using the Folding@home distributed
      computing system, we generated thousands of independent trajectories in an
      implicit solvent model, totaling over 2.73 ms of simulations. A small number of
      these trajectories folded; the folding proceeded along several distinct routes
      and the system folded into two distinct three-stranded beta-sheet conformations,
      showing that the folding mechanism of this system is distinctly heterogeneous.

PMID- 19383446
TI  - Adhesive dynamics simulation of G-protein-mediated chemokine-activated neutrophil
      adhesion.
AB  - To reach sites of inflammation, a blood-borne neutrophil first rolls over the
      vessel wall, becoming firmly adherent on activation, and then transmigrates
      through the endothelium. In this study, we simulate the transition to firm
      adhesion via chemokine-induced integrin activation. To recreate the transition
      from rolling to firm adhesion, we use an integrated signaling adhesive dynamics
      simulation that includes selectin, integrin, and chemokine interactions between
      the cell and an adhesive substrate. Integrin bonds are of low affinity until
      activated by chemokine binding to G-protein coupled receptors on the model cell.
      The signal propagates within the cell through probabilistic diffusion and
      reaction of the signaling elements to induce the high-affinity integrins required
      for firm adhesion. This model showed that integrins become progressively active
      as cells roll and interact with chemokines, leading to a slight slowing before
      firm adhesion on a timescale similar to that observed in experiments. Increasing
      the density of chemokine resulted in decreases in the rolling time before
      stopping, consistent with experimental observations. However, a limit is reached
      where further increases in chemokine density do not increase adhesion. We found
      that the timescale for integrin activation correlated with the time to stop.
      Further, altering parameters within the intracellular signaling cascade that
      changed the speed of integrin activation, such as effector activation and
      dissociation rates, correspondingly affected the time to firm adhesion. For all
      conditions tested, the number of active integrin bonds at the point of firm
      adhesion was relatively constant. The model predicts that the time to stop would
      be relatively independent of selectin or integrin density, but strongly dependent
      on the shear rate because higher shear rates limit the intrinsic activation rate
      of integrins and require more integrins for adhesion.

PMID- 19383447
TI  - Elasticity and rupture of a multi-domain neural cell adhesion molecule complex.
AB  - The neural cell adhesion molecule (NCAM) plays an important role in nervous
      system development. NCAM forms a complex between its terminal domains Ig1 and
      Ig2. When NCAM of cell A and of cell B connect to each other through complexes
      Ig12(A)/Ig12(B), the relative mobility of cells A and B and membrane tension
      exerts a force on the Ig12(A)/Ig12(B) complex. In this study, we investigated the
      response of the complex to force, using steered molecular dynamics. Starting from
      the structure of the complex from the Ig1-Ig2-Ig3 fragment, we first demonstrated
      that the complex, which differs in dimensions from a previous structure from the
      Ig1-Ig2 fragment in the crystal environment, assumes the same extension when
      equilibrated in solvent. We then showed that, when the Ig12(A)/Ig12(B) complex is
      pulled apart with forces 30-70 pN, it exhibits elastic behavior (with a spring
      constant of approximately 0.03 N/m) because of the relative reorientation of
      domains Ig1 and Ig2. At higher forces, the complex ruptures; i.e., Ig12(A) and
      Ig12(B) separate. The interfacial interactions between Ig12(A) and Ig12(B),
      monitored throughout elastic extension and rupture, identify E16, F19, K98, and
      L175 as key side chains stabilizing the complex.

PMID- 19383448
TI  - A look-ahead model for the elongation dynamics of transcription.
AB  - This article introduces a chemical kinetic model of the transcriptional
      elongation dynamics of RNA polymerase. The model's novel concept is a look-ahead
      feature, in which nucleotides bind reversibly to the DNA before being
      incorporated covalently into the nascent RNA chain. Analytical and computational
      methods for studying the behavior of the look-ahead model are introduced, and
      several approaches to parameter estimation are tested on synthetic and also on
      actual experimental data. Two types of experimental data are considered: 1), the
      mean velocity of RNA polymerase as a function of the ambient concentrations of
      the ribonucleoside triphosphates; and 2), the distribution of time intervals
      between the forward steps of RNA polymerase. By separately fitting the look-ahead
      model to these two types of data, we obtain estimates of the model parameters.
      The most difficult parameter to estimate is the width of the look-ahead window.
      Both types of data suggest a small window size, but the second type does a better
      job of distinguishing the different window sizes. These latter data rule out a
      window size of 1, and they strongly suggest a look-ahead window that is
      approximately four bases in width. Additional experiments to determine the window
      size are proposed.

PMID- 19383449
TI  - The stability of cellulose: a statistical perspective from a coarse-grained model
      of hydrogen-bond networks.
AB  - A critical roadblock to the production of biofuels from lignocellulosic biomass
      is the efficient degradation of crystalline microfibrils of cellulose to glucose.
      A microscopic understanding of how different physical conditions affect the
      overall stability of the crystalline structure of microfibrils could facilitate
      the design of more effective protocols for their degradation. One of the
      essential physical interactions that stabilizes microfibrils is a network of
      hydrogen (H) bonds: both intrachain H-bonds between neighboring monomers of a
      single cellulose polymer chain and interchain H-bonds between adjacent chains. We
      construct a statistical mechanical model of cellulose assembly at the resolution
      of explicit hydrogen-bond networks. Using the transfer matrix method, the
      partition function and the subsequent statistical properties are evaluated. With
      the help of this lattice-based model, we capture the plasticity of the H-bond
      network in cellulose due to frustration and redundancy in the placement of H
      bonds. This plasticity is responsible for the stability of cellulose over a wide
      range of temperatures. Stable intrachain and interchain H-bonds are identified as
      a function of temperature that could possibly be manipulated toward rational
      destruction of crystalline cellulose.

PMID- 19383450
TI  - Correlated diffusion of membrane proteins and their effect on membrane viscosity.
AB  - We extend the Saffman theory of membrane hydrodynamics to account for the
      correlated motion of membrane proteins, along with the effect of protein
      concentration on that correlation and on the response of the membrane to
      stresses. Expressions for the coupling diffusion coefficients of protein pairs
      and their concentration dependence are derived in the limit of small protein size
      relative to the interprotein separation. The additional role of membrane
      viscosity as determining the characteristic length scale for membrane response
      leads to unusual concentration effects at large separation-the transverse
      coupling increases with protein concentration, whereas the longitudinal one
      becomes concentration-independent.

PMID- 19383451
TI  - Microtubule depolymerization by the Kinesin-8 motor Kip3p: a mathematical model.
AB  - Proteins from the kinesin-8 family promote microtubule (MT) depolymerization, a
      process thought to be important for the control of microtubule length in living
      cells. In addition to this MT shortening activity, kinesin 8s are motors that
      show plus-end directed motility on MTs. Here we describe a simple model that
      incorporates directional motion and destabilization of the MT plus-end by kinesin
      8. Our model quantitatively reproduces the key features of length-versus-time
      traces for stabilized MTs in the presence of purified kinesin 8, including length
      dependent depolymerization. Comparison of model predictions with experiments
      suggests that kinesin 8 depolymerizes processively, i.e., one motor can remove
      multiple tubulin dimers from a stabilized MT. Fluctuations in MT length as a
      function of time are related to depolymerization processivity. We have also
      determined the parameter regime in which the rate of MT depolymerization is
      length dependent: length-dependent depolymerization occurs only when MTs are
      sufficiently short; this crossover is sensitive to the bulk motor concentration.

PMID- 19383452
TI  - Electrostatic regulation of genome packaging in human hepatitis B virus.
AB  - Hepatitis B virus (HBV) is a contagious human pathogen causing liver diseases
      such as cirrhosis and hepatocellular carcinoma. An essential step during HBV
      replication is packaging of a pregenomic (pg) RNA within the capsid of core
      antigens (HBcAgs) that each contains a flexible C-terminal tail rich in arginine
      residues. Mutagenesis experiments suggest that pgRNA encapsidation hinges on its
      strong electrostatic interaction with oppositely charged C-terminal tails of the
      HBcAgs, and that the net charge of the capsid and C-terminal tails determines the
      genome size and nucleocapsid stability. Here, we elucidate the biophysical basis
      for electrostatic regulation of pgRNA packaging in HBV by using a coarse-grained
      molecular model that explicitly accounts for all nonspecific interactions among
      key components within the nucleocapsid. We find that for mutants with variant C
      terminal length, an optimal genome size minimizes an appropriately defined
      thermodynamic free energy. The thermodynamic driving force of RNA packaging
      arises from a combination of electrostatic interactions and molecular excluded
      volume effects. The theoretical predictions of the RNA length and nucleocapsid
      internal structure are in good agreement with available experiments for the wild
      type HBV and mutants with truncated HBcAg C-termini.

PMID- 19383453
TI  - All-atom contact model for understanding protein dynamics from crystallographic B
      factors.
AB  - An all-atom local contact model is described that can be used to predict protein
      motions underlying isotropic crystallographic B-factors. It uses a mean-field
      approximation to represent the motion of an atom in a harmonic potential
      generated by the surrounding atoms resting at their equilibrium positions. Based
      on a 400-ns molecular dynamics simulation of ubiquitin in explicit water, it is
      found that each surrounding atom stiffens the spring constant by a term that on
      average scales exponentially with the interatomic distance. This model combines
      features of the local density model by Halle and the local contact model by Zhang
      and Bruschweiler. When applied to a nonredundant set of 98 ultra-high resolution
      protein structures, an average correlation coefficient of 0.75 is obtained for
      all atoms. The systematic inclusion of crystal contact contributions and fraying
      effects is found to enhance the performance substantially. Because the
      computational cost of the local contact model scales linearly with the number of
      protein atoms, it is applicable to proteins of any size for the prediction of B
      factors of both backbone and side-chain atoms. The model performs as well as or
      better than several other models tested, such as rigid-body motional models, the
      local density model, and various forms of the elastic network model. It is
      concluded that at the currently achievable level of accuracy, collective
      intramolecular motions are not essential for the interpretation of B-factors.

PMID- 19383454
TI  - Solution- and adsorbed-state structural ensembles predicted for the statherin
      hydroxyapatite system.
AB  - We have developed a multiscale structure prediction technique to study solution-
      and adsorbed-state ensembles of biomineralization proteins. The algorithm employs
      a Metropolis Monte Carlo-plus-minimization strategy that varies all torsional and
      rigid-body protein degrees of freedom. We applied the technique to fold
      statherin, starting from a fully extended peptide chain in solution, in the
      presence of hydroxyapatite (HAp) (001), (010), and (100) monoclinic crystals.
      Blind (unbiased) predictions capture experimentally observed macroscopic and high
      resolution structural features and show minimal statherin structural change upon
      adsorption. The dominant structural difference between solution and adsorbed
      states is an experimentally observed folding event in statherin's helical binding
      domain. Whereas predicted statherin conformers vary slightly at three different
      HAp crystal faces, geometric and chemical similarities of the surfaces allow
      structurally promiscuous binding. Finally, we compare blind predictions with
      those obtained from simulation biased to satisfy all previously published solid
      state NMR (ssNMR) distance and angle measurements (acquired from HAp-adsorbed
      statherin). Atomic clashes in these structures suggest a plausible, alternative
      interpretation of some ssNMR measurements as intermolecular rather than
      intramolecular. This work demonstrates that a combination of ssNMR and structure
      prediction could effectively determine high-resolution protein structures at
      biomineral interfaces.

PMID- 19383455
TI  - Extracellular space attenuates the effect of gap junctional remodeling on wave
      propagation: a computational study.
AB  - Ionic channels and gap junctions are remodeled in cells from the 5-day epicardial
      border zone (EBZ) of the healing canine infarct. The main objective of the study
      was to determine the effect of gap junctional conductance (Gj) remodeling and
      Cx43 redistribution to the lateral membrane on conduction velocity (theta) and
      anisotropic ratio, and how gap junctional remodeling is modulated by the
      extracellular space. We first implemented subcellular monodomain and two-domain
      computer models of normal epicardium (NZ) to understand how extracellular space
      modulates the relationship between Gj and theta in NZ. We found that the
      extracellular space flattens the Gj-theta relationship, thus theta becomes less
      sensitive to changes in Gj. We then investigated the functional consequences of
      Gj remodeling and Cx43 distribution in subcellular computer models of cells of
      the outer pathway (IZo) and central pathway (IZc) of reentrant circuits. In IZo
      cells, side-to-side (transverse) Gj is 10% the value in NZ cells. Such Gj
      remodeling causes a 45% decrease in transverse theta (theta(T)). Inclusion of an
      extracellular space reduces the decrease in theta(T) to 31%. In IZc cells, Cx43
      redistribution along the lateral membrane results in a 29% increase in theta(T).
      That increase in theta(T) is a consequence of the decrease in access resistance
      to the Cx43 plaques that occur with the Cx43 redistribution. Extracellular space
      reduces the increase in theta(T) to 10%. IN CONCLUSION: 1), The extracellular
      space included in normal epicardial simulations flattens the Gj-theta
      relationship with theta becoming less sensitive to changes in Gj. 2), The
      extracellular space attenuates the effects of gap junction epicardial border zone
      remodeling (i.e., Gj reduction and Cx43 lateralization) on theta(T).

PMID- 19383456
TI  - The effect of a spatially heterogeneous transmural water flux on concentration
      polarization of low density lipoprotein in arteries.
AB  - Uptake of low density lipoprotein (LDL) by the arterial wall is likely to play a
      key role in atherogenesis. A particular process that may cause vascular scale
      heterogeneity in the rate of transendothelial LDL transport is the formation of a
      flow-dependent LDL concentration polarization layer on the luminal surface of the
      arterial endothelium. In this study, the effect of a spatially heterogeneous
      transmural water flux (that traverses the endothelium only via interendothelial
      cell clefts) on such concentration polarization is investigated numerically.
      Unlike in previous investigations, realistic intercellular cleft dimensions are
      used here and several values of LDL diffusivity are considered. Particular
      attention is paid to the spatially averaged LDL concentration adjacent to
      different regions of the endothelial surface, as such measures may be relevant to
      the rate of transendothelial LDL transport. It is demonstrated in principle that
      a heterogeneous transmural water flux can act to enhance such measures, and cause
      them to develop a shear dependence (in addition to that caused by vascular scale
      flow features, affecting the overall degree of LDL concentration polarization).
      However, it is shown that this enhancement and additional shear dependence are
      likely to be negligible for a physiologically realistic transmural flux velocity
      of 0.0439 mum s(-1) and an LDL diffusivity (in blood plasma) of 28.67 mum(2) s(
      1). Hence, the results imply that vascular scale studies of LDL concentration
      polarization are justified in ignoring the effect of a spatially heterogeneous
      transmural water flux.

PMID- 19383457
TI  - Transitions between closed and open conformations of TolC: the effects of ions in
      simulations.
AB  - Bacteria, such as Escherichia coli, use multidrug efflux pumps to export toxic
      substrates through their cell membranes. Upon formation of an efflux pump, the
      aperture of its outer membrane protein TolC opens and thereby enables the
      extrusion of substrate molecules. The specialty of TolC is its ability to dock to
      different transporters, making it a highly versatile export protein. Within this
      study, the transition between two conformations of TolC that are both available
      as crystal structures was investigated using all-atom molecular dynamics
      simulations. To create a partially open conformation from a closed one, the
      stability of the periplasmic aperture was weakened by a double point mutation at
      the constricting ring, which removes some salt bridges and hydrogen bonds. These
      mutants, which showed partial opening in previous experiments, did not
      spontaneously open during a 20-ns equilibration at physiological values of the
      KCl solution. Detailed analysis of the constricting ring revealed that the
      cations of the solvent were able to constitute ionic bonds in place of the
      removed salt bridges, which inhibited the opening of the aperture in simulations.
      To remove the ions from these binding positions within the available simulation
      time, an extra force was applied onto the ions. To keep the effect of this
      additional force rather flexible, it was applied in form of an artificial
      external electric field perpendicular to the membrane. Depending on the field
      direction and the ion concentration, these simulations led to a partial opening.
      In experiments, this energy barrier for the ions can be overcome by thermal
      fluctuations on a longer timescale.

PMID- 19383458
TI  - A model of action potentials and fast Ca2+ dynamics in pancreatic beta-cells.
AB  - We examined the ionic mechanisms mediating depolarization-induced spike activity
      in pancreatic beta-cells. We formulated a Hodgkin-Huxley-type ionic model for the
      action potential (AP) in these cells based on voltage- and current-clamp results
      together with measurements of Ca(2+) dynamics in wild-type and Kv2.1 null mouse
      islets. The model contains an L-type Ca(2+) current, a "rapid" delayed-rectifier
      K(+) current, a small slowly-activated K(+) current, a Ca(2+)-activated K(+)
      current, an ATP-sensitive K(+) current, a plasma membrane calcium-pump current
      and a Na(+) background current. This model, coupled with an equation describing
      intracellular Ca(2+) homeostasis, replicates beta-cell AP and Ca(2+) changes
      during one glucose-induced spontaneous spike, the effects of blocking K(+)
      currents with different inhibitors, and specific complex spike in mouse islets
      lacking Kv2.1 channels. The currents with voltage-independent gating variables
      can also be responsible for burst behavior. Original features of this model
      include new equations for L-type Ca(2+) current, assessment of the role of rapid
      delayed-rectifier K(+) current, and Ca(2+)-activated K(+) currents, demonstrating
      the important roles of the Ca(2+)-pump and background currents in the APs and
      bursts. This model provides acceptable fits to voltage-clamp, AP, and Ca(2+)
      concentration data based on in silico analysis.

PMID- 19383459
TI  - Disturb or stabilize? A molecular dynamics study of the effects of resorcinolic
      lipids on phospholipid bilayers.
AB  - Resorcinolic lipids, or resorcinols, are commonly found in plant membranes. They
      consist of a substituted benzene ring forming the hydrophilic lipid head,
      attached to an alkyl chain forming the hydrophobic tail. Experimental results
      show alternative effects of resorcinols on lipid membranes. Depending on whether
      they are added to lipid solutions before or after the formation of the liposomes,
      they either stabilize or destabilize these liposomes. Here we use atomistic
      molecular dynamics simulations to elucidate the molecular nature of this dual
      effect. Systems composed of either one of three resorcinol homologs, differing in
      the alkyl tail length, interacting with dimyristoylphosphatidylcholine lipid
      bilayers were studied. It is shown that resorcinols preincorporated into bilayers
      induce order within the lipid acyl chains, decrease the hydration of the lipid
      headgroups, and make the bilayers less permeable to water. In contrast,
      simulations in which the resorcinols are incorporated from the aqueous solution
      into a preformed phospholipid bilayer induce local disruption, leading to either
      transient pore formation or even complete rupture of the membrane. In line with
      the experimental data, our simulations thus demonstrate that resorcinols can
      either disturb or stabilize the membrane structure, and offer a detailed view of
      the underlying molecular mechanism.

PMID- 19383460
TI  - Model studies of the dynamics of bacterial flagellar motors.
AB  - The bacterial flagellar motor is a rotary molecular machine that rotates the
      helical filaments that propel swimming bacteria. Extensive experimental and
      theoretical studies exist on the structure, assembly, energy input, power
      generation, and switching mechanism of the motor. In a previous article, we
      explained the general physics underneath the observed torque-speed curves with a
      simple two-state Fokker-Planck model. Here, we further analyze that model,
      showing that 1), the model predicts that the two components of the ion motive
      force can affect the motor dynamics differently, in agreement with latest
      experiments; 2), with explicit consideration of the stator spring, the model also
      explains the lack of dependence of the zero-load speed on stator number in the
      proton motor, as recently observed; and 3), the model reproduces the stepping
      behavior of the motor even with the existence of the stator springs and predicts
      the dwell-time distribution. The predicted stepping behavior of motors with two
      stators is discussed, and we suggest future experimental procedures for
      verification.

PMID- 19383461
TI  - Long-range coupling in an allosteric receptor revealed by mutant cycle analysis.
AB  - The functional coupling of residues that are far apart in space is the
      quintessential property of allosteric proteins. For example, in Cys-loop
      receptors, the gating of an intrinsic ion channel is allosterically regulated by
      the binding of small molecule neurotransmitters 50-60 A from the channel gate.
      Some residues near the binding site must have as their primary function the
      communication of the binding event to the gating region. These gating pathway
      residues are essential to function, but their identification and characterization
      can be challenging. This work introduces a simple strategy, derived from mutant
      cycle analysis, for identifying gating pathway residues using macroscopic
      measurements alone. In the exemplar Cys-loop receptor, the nicotinic
      acetylcholine receptor, a well-characterized reporter mutation (betaL9'S) known
      to impact gating, was combined with mutations of target residues in the ligand
      binding domain hypothesized or previously found to be functionally significant. A
      mutant cycle analysis of the macroscopic EC(50) measurements can then provide
      insights into the role of the target residue. This new method, elucidating long
      range functional coupling in allosteric receptors, can be applied to several
      reporter mutations in a wide variety of receptors to identify previously
      characterized and novel mutations that impact the gating pathway. We support our
      interpretation of macroscopic data with single-channel studies. Elucidating long
      range functional coupling in allosteric receptors should be broadly applicable to
      determining functional roles of residues in allosteric receptors.

PMID- 19383462
TI  - Prestin's anion transport and voltage-sensing capabilities are independent.
AB  - The integral membrane protein prestin, a member of the SLC26 anion transporter
      family, is responsible for the voltage-driven electromotility of mammalian outer
      hair cells. It was argued that the evolution of prestin's motor function required
      a loss of the protein's transport capabilities. Instead, it was proposed that
      prestin manages only an abortive hemicycle that results in the trapped anion
      acting as a voltage sensor, to generate the motor's signature gating charge
      movement or nonlinear capacitance. We demonstrate, using classical radioactive
      anion ([(14)C]formate and [(14)C]oxalate) uptake studies, that in contrast to
      previous observations, prestin is able to transport anions. The prestin-dependent
      uptake of both these anions was twofold that of cells transfected with vector
      alone, and comparable to SLC26a6, prestin's closest phylogenetic relative.
      Furthermore, we identify a potential chloride-binding site in which the mutations
      of two residues (P328A and L326A) preserve nonlinear capacitance, yet negate
      anion transport. Finally, we distinguish 12 charged residues out of 22, residing
      within prestin's transmembrane regions, that contribute to unitary charge
      movement, i.e., voltage sensing. These data redefine our mechanistic concept of
      prestin.

PMID- 19383463
TI  - Structure of a double transmembrane fragment of a G-protein-coupled receptor in
      micelles.
AB  - The structure and dynamic properties of an 80-residue fragment of Ste2p, the G
      protein-coupled receptor for alpha-factor of Saccharomyces cerevisiae, was
      studied in LPPG micelles with the use of solution NMR spectroscopy. The fragment
      Ste2p(G31-T110) (TM1-TM2) consisted of 19 residues from the N-terminal domain,
      the first TM helix (TM1), the first cytoplasmic loop, the second TM helix (TM2),
      and seven residues from the first extracellular loop. Multidimensional NMR
      experiments on [(15)N], [(15)N, (13)C], [(15)N, (13)C, (2)H]-labeled TM1-TM2 and
      on protein fragments selectively labeled at specific amino acid residues or
      protonated at selected methyl groups resulted in >95% assignment of backbone and
      side-chain nuclei. The NMR investigation revealed the secondary structure of
      specific residues of TM1-TM2. TALOS constraints and NOE connectivities were used
      to calculate a structure for TM1-TM2 that was highlighted by the presence of
      three alpha-helices encompassing residues 39-47, 49-72, and 80-103, with higher
      flexibility around the internal Arg(58) site of TM1. RMSD values of individually
      superimposed helical segments 39-47, 49-72, and 80-103 were 0.25 +/- 0.10 A, 0.40
      +/- 0.13 A, and 0.57 +/- 0.19 A, respectively. Several long-range interhelical
      connectivities supported the folding of TM1-TM2 into a tertiary structure
      typified by a crossed helix that splays apart toward the extracellular regions
      and contains considerable flexibility in the G(56)VRSG(60) region. (15)N
      relaxation and hydrogen-deuterium exchange data support a stable fold for the TM
      parts of TM1-TM2, whereas the solvent-exposed segments are more flexible. The NMR
      structure is consistent with the results of biochemical experiments that
      identified the ligand-binding site within this region of the receptor.

PMID- 19383464
TI  - Structure of self-aggregated alamethicin in ePC membranes detected by pulsed
      electron-electron double resonance and electron spin echo envelope modulation
      spectroscopies.
AB  - PELDOR spectroscopy was exploited to study the self-assembled super-structure of
      the [Glu(OMe)(7,18,19)]alamethicin molecules in vesicular membranes at peptide to
      lipid molar ratios in the range of 1:70-1:200. The peptide molecules were site
      specifically labeled with TOAC electron spins. From the magnetic dipole-dipole
      interaction between the nitroxides of the monolabeled constituents and the PELDOR
      decay patterns measured at 77 K, intermolecular-distance distribution functions
      were obtained and the number of aggregated molecules (n approximately 4) was
      estimated. The distance distribution functions exhibit a similar maximum at 2.3
      nm. In contrast to Alm16, for Alm1 and Alm8 additional maxima were recorded at
      3.2 and approximately 5.2 nm. From ESEEM experiments and based on the membrane
      polarity profiles, the penetration depths of the different spin-labeled positions
      into the membrane were qualitatively estimated. It was found that the water
      accessibility of the spin-labels follows the order TOAC-1 > TOAC-8 approximately
      TOAC-16. The geometric data obtained are discussed in terms of a penknife
      molecular model. At least two peptide chains are aligned parallel and eight ester
      groups of the polar Glu(OMe)(18,19) residues are suggested to stabilize the self
      aggregate superstructure.

PMID- 19383465
TI  - Lipid raft composition modulates sphingomyelinase activity and ceramide-induced
      membrane physical alterations.
AB  - Lipid rafts and ceramide (Cer)-platforms are membrane domains that play an
      important role in several biological processes. Cer-platforms are commonly formed
      in the plasma membrane by the action of sphingomyelinase (SMase) upon hydrolysis
      of sphingomyelin (SM) within lipid rafts. The interplay among SMase activity,
      initial membrane properties (i.e., phase behavior and lipid lateral organization)
      and lipid composition, and the amount of product (Cer) generated, and how it
      modulates membrane properties were studied using fluorescence methodologies in
      model membranes. The activity of SMase was evaluated by following the hydrolysis
      of radioactive SM. It was observed that 1), the enzyme activity and extent of
      hydrolysis are strongly dependent on membrane physical properties but not on
      substrate content, and are higher in raft-like mixtures, i.e., mixtures with
      liquid-disordered/liquid-ordered phase separation; and 2), Cer-induced
      alterations are also dependent on membrane composition, specifically the
      cholesterol (Chol) content. In the lowest-Chol range, Cer segregates together
      with SM into small ( approximately 8.5 nm) Cer/SM-gel domains. With increasing
      Chol, the ability of Cer to recruit SM and form gel domains strongly decreases.
      In the high-Chol range, a Chol-enriched/SM-depleted liquid-ordered phase
      predominates. Together, these data suggest that in biological membranes, Chol in
      particular and raft domains in general play an important role in modulating SMase
      activity and regulating membrane physical properties by restraining Cer-induced
      alterations.

PMID- 19383466
TI  - Orientation and dynamics of peptides in membranes calculated from 2H-NMR data.
AB  - Solid-state (2)H-NMR is routinely used to determine the alignment of membrane
      bound peptides. Here we demonstrate that it can also provide a quantitative
      measure of the fluctuations around the distinct molecular axes. Using several
      dynamic models with increasing complexity, we reanalyzed published (2)H-NMR data
      on two representative alpha-helical peptides: 1), the amphiphilic antimicrobial
      peptide PGLa, which permeabilizes membranes by going from a monomeric surface
      bound to a dimeric tilted state and finally inserting as an oligomeric pore; and
      2), the hydrophobic WALP23, which is a typical transmembrane segment, although
      previous analysis had yielded helix tilt angles much smaller than expected from
      hydrophobic mismatch and molecular dynamics simulations. Their (2)H-NMR data were
      deconvoluted in terms of the two main helix orientation angles (representing the
      time-averaged peptide tilt and azimuthal rotation), as well as the amplitudes of
      fluctuation about the corresponding molecular axes (providing the dynamic
      picture). The mobility of PGLa is found to be moderate and to correlate well with
      the respective oligomeric states. WALP23 fluctuates more vigorously, now in
      better agreement with the molecular dynamics simulations and mismatch
      predictions. The analysis demonstrates that when (2)H-NMR data are fitted to
      extract peptide orientation angles, an explicit representation of the peptide
      rigid-body angular fluctuations should be included.

PMID- 19383467
TI  - Influence of whole-body dynamics on 15N PISEMA NMR spectra of membrane proteins:
      a theoretical analysis.
AB  - Membrane proteins and peptides exhibit a preferred orientation in the lipid
      bilayer while fluctuating in an anisotropic manner. Both the orientation and the
      dynamics have direct functional implications, but motions are usually not
      accessible, and structural descriptions are generally static. Using simulated
      data, we analyze systematically the impact of whole-body motions on the peptide
      orientations calculated from two-dimensional polarization inversion spin exchange
      at the magic angle (PISEMA) NMR. Fluctuations are found to have a significant
      effect on the observed spectra. Nevertheless, wheel-like patterns are still
      preserved, and it is possible to determine the average peptide tilt and azimuthal
      rotation angles using simple static models for the spectral fitting. For helical
      peptides undergoing large-amplitude fluctuations, as in the case of transmembrane
      monomers, improved fits can be achieved using an explicit dynamics model that
      includes Gaussian distributions of the orientational parameters. This method
      allows extracting the amplitudes of fluctuations of the tilt and azimuthal
      rotation angles. The analysis is further demonstrated by generating first a
      virtual PISEMA spectrum from a molecular dynamics trajectory of the model
      peptide, WLP23, in a lipid membrane. That way, the dynamics of the system from
      which the input spectrum originates is completely known at atomic detail and can
      thus be directly compared with the dynamic output obtained from the fit. We find
      that fitting our dynamics model to the polar index slant angles wheel gives an
      accurate description of the amplitude of underlying motions, together with the
      average peptide orientation.

PMID- 19383468
TI  - HIV-1 Nef perturbs artificial membranes: investigation of the contribution of the
      myristoyl anchor.
AB  - Nef, an accessory protein from human immunodeficiency virus type 1, is critical
      for optimal viral replication and pathogenesis. Here, we analyzed the influence
      of full-length myristoylated and nonmyristoylated Nef on artificial lipid
      bilayers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). By
      means of cosedimentation assays, we found that neither nonmyristoylated nor
      myristoylated Nef stably binds to POPC unilamellar vesicles. Time-resolved
      ellipsometry rather indicates that the proteins perturb the assembly of POPC
      planar bilayers. This observation was corroborated by fluorescence and scanning
      force microscopy, suggesting that membrane disordering occurs upon interaction of
      full-length myristoylated and nonmyristoylated Nef with planar POPC membranes
      immobilized on SiO(2) surfaces resulting in loss of material from the surface.
      The membrane perturbations were further investigated by vesicle release
      experiments, demonstrating that the disordering results in defects through which
      the fluorophor carboxyfluorescein can pass. From these results, we conclude that
      Nef is capable of disordering and perturbing lipid membranes and that the
      myristoyl group is not the decisive determinant for the action of the protein on
      lipid membranes.

PMID- 19383469
TI  - Transmembrane helical domain of the cannabinoid CB1 receptor.
AB  - Brain cannabinoid (CB(1)) receptors are G-protein coupled receptors and belong to
      the rhodopsin-like subfamily. A homology model of the inactive state of the CB(1)
      receptor was constructed using the x-ray structure of beta(2)-adrenergic receptor
      (beta(2)AR) as the template. We used 105 ns duration molecular-dynamics
      simulations of the CB(1) receptor embedded in a 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) bilayer to gain some insight into the structure and
      function of the CB(1) receptor. As judged from the root mean-square deviations
      combined with the detailed structural analyses, the helical bundle of the CB(1)
      receptor appears to be fully converged in 50 ns of the simulation. The results
      reveal that the helical bundle structure of the CB(1) receptor maintains a
      topology quite similar to the x-ray structures of G-protein coupled receptors
      overall. It is also revealed that the CB(1) receptor is stabilized by the
      formation of extensive, water-mediated H-bond networks, aromatic stacking
      interactions, and receptor-lipid interactions within the helical core region. It
      is likely that these interactions, which are often specific to functional motifs,
      including the S(N)LAxAD, D(E)RY, CWxP, and NPxxY motifs, are the molecular
      constraints imposed on the inactive state of the CB(1) receptor. It appears that
      disruption of these specific interactions is necessary to release the molecular
      constraints to achieve a conformational change of the receptor suitable for G
      protein activation.

PMID- 19383470
TI  - Free energies of molecular bound states in lipid bilayers: lethal concentrations
      of antimicrobial peptides.
AB  - The lipid matrix, or the lipid bilayer, of cell membranes is a natural binding
      site for amphipathic molecules, including antimicrobial peptides, pore-forming
      proteins, and many drugs. The unique property of pore-forming antimicrobial
      peptides is that they exhibit a threshold concentration (called the lethal
      concentration or the minimum inhibitory concentration) for activity, below which
      no effect is seen. Without this property, antimicrobial peptides would not be
      effective self-defense weapons, because they would have harmed all cells at any
      concentration. The question is what gives rise to this unique property? This
      study provides a free energy description for the origin of a threshold
      concentration. The same free energy applied differently also explains the binding
      of drugs that shows no threshold concentrations. The idea is compared with
      theories of micellar solutions that require a large oligomer size (n 15) to
      achieve a threshold concentration. The elasticity of lipid bilayers makes the
      phenomena in membranes different. The majority of antimicrobial peptides have a
      large negative binding energy to the bilayer interface, but the binding causes an
      expansion in the membrane area, or equivalently a thinning in the membrane
      thickness. This elastic energy of membrane thinning elevates the energy level of
      interfacial binding with the peptide concentration, hence gives rise to a
      threshold concentration for forming pores containing as few as four peptides.

PMID- 19383471
TI  - Cardiac myosin binding protein-C is essential for thick-filament stability and
      flexural rigidity.
AB  - Using atomic force microscopy, we examined the contribution of cardiac myosin
      binding protein-C (cMyBP-C) to thick-filament length and flexural rigidity.
      Native thick filaments were isolated from the hearts of transgenic mice bearing a
      truncation mutation of cMyBP-C (t/t) that results in no detectable cMyBP-C and
      from age-matched wild-type controls (+/+). Atomic force microscopy images of
      these filaments were evaluated with an automated analysis algorithm that
      identified filament position and shape. The t/t thick-filament length (1.48 +/-
      0.02 microm) was significantly (P < 0.01) shorter than +/+ (1.56 +/- 0.02
      microm). This 5%-shorter thick-filament length in the t/t was reflected in 4%
      significantly shorter sarcomere lengths of relaxed isolated cardiomyocytes of the
      t/t (1.97 +/- 0.01 microm) compared to +/+ (2.05 +/- 0.01 microm). To determine
      if cMyBP-C contributes to the mechanical properties of thick filaments, we used
      statistical polymer chain mechanics to calculate a per-filament-specific
      persistence length, an index of flexural rigidity directly proportional to
      Young's modulus. Thick-filament-specific persistence length in the t/t (373 +/-
      62 microm) was significantly lower than in +/+ (639 +/- 101 microm). Accordingly,
      Young's modulus of t/t thick filaments was approximately 60% of +/+. These
      results provide what we consider a new understanding for the critical role of
      cMyBP-C in defining normal cardiac output by sustaining force and muscle
      stiffness.

PMID- 19383472
TI  - Time course and strain dependence of ADP release during contraction of
      permeabilized skeletal muscle fibers.
AB  - A phosphorylated, single cysteine mutant of nucleoside diphosphate kinase,
      labeled with N-[2-(iodoacetamido)ethyl]-7-diethylaminocoumarin-3-carboxamide (P
      approximately NDPK-IDCC), was used as a fluorescence probe for time-resolved
      measurement of changes in [MgADP] during contraction of single permeabilized
      rabbit psoas fibers. The dephosphorylation of the phosphorylated protein by MgADP
      occurs within the lattice environment of permeabilized fibers with a second-order
      rate constant at 12 degrees C of 10(5) M(-1) s(-1). This dephosphorylation is
      accompanied by a change in coumarin fluorescence. We report the time course of P
      approximately NDPK-IDCC dephosphorylation during the period of active isometric
      force redevelopment after quick release of fiber strain at pCa(2+) of 4.5. After
      a rapid length decrease of 0.5% was applied to the fiber, the extra NDPK-IDCC
      produced during force recovery, above the value during the approximately steady
      state of isometric contraction, was 2.7 +/- 0.6 microM and 4.7 +/- 1.5 microM at
      12 and 20 degrees C, respectively. The rates of P approximately NDPK-IDCC
      dephosphorylation during force recovery were 28 and 50 s(-1) at 12 and 20 degrees
      C, respectively. The time courses of isometric force and P approximately NDPK
      IDCC dephosphorylation were simulated using a seven-state reaction scheme.
      Relative isometric force was modeled by changes in the occupancy of strongly
      bound A.M.ADP.P(i) and A.M.ADP states. A strain-sensitive A.M.ADP isomerization
      step was rate-limiting (3-6 s(-1)) in the cross-bridge turnover during isometric
      contraction. At 12 degrees C, the A.M.ADP.P(i) and the pre- and postisomerization
      A.M.ADP states comprised 56%, 38%, and 7% of the isometric force-bearing AM
      states, respectively. At 20 degrees C, the force-bearing A.M.ADP.P(i) state was a
      lower proportion of the total force-bearing states (37%), whereas the proportion
      of postisomerization A.M.ADP states was higher (19%). The simulations suggested
      that release of cross-bridge strain caused rapid depopulation of the
      preisomerization A.M.ADP state and transient accumulation of MgADP in the
      postisomerization A.M.ADP state. Hence, the strain-sensitive isomerization of
      A.M.ADP seems to explain the rate of change of P approximately NDPK-IDCC
      dephosphorylation during force recovery. The temperature-dependent isometric
      distribution of myosin states is consistent with the previous observation of a
      small decrease in amplitude of the P(i) transient during force recovery at 20
      degrees C and the current observation of an increase in amplitude of the ADP
      sensitive NDPK-IDCC transient.

PMID- 19383473
TI  - Effect of anions on the binding and oxidation of divalent manganese and iron in
      modified bacterial reaction centers.
AB  - The influence of different anions on the binding and oxidation of manganous and
      ferrous cations was studied in four mutants of bacterial reaction centers that
      can bind and oxidize these metal ions. Light-minus-dark difference optical and
      electron paramagnetic resonance spectroscopies were applied to monitor electron
      transfer from bound divalent metal ions to the photo-oxidized bacteriochlorophyll
      dimer in the presence of five different anions. At pH 7, bicarbonate was found to
      be the most effective for both manganese and iron binding, with dissociation
      constants around 1 muM in three of the mutants. The pH dependence of the
      dissociation constants for manganese revealed that only bicarbonate and acetate
      were able to facilitate the binding and oxidation of the metal ion between pH 6
      and 8 where the tight binding in their absence could not otherwise be
      established. The data are consistent with two molecules of bicarbonate or one
      molecule of acetate binding to the metal binding site. For ferrous ion, the
      binding and oxidation was facilitated not only by bicarbonate and acetate, but
      also by citrate. Electron paramagnetic resonance spectra suggest differences in
      the arrangement of the iron ligands in the presence of the various anions.

PMID- 19383474
TI  - Surface-bound casein modulates the adsorption and activity of kinesin on SiO2
      surfaces.
AB  - Conventional kinesin is routinely adsorbed to hydrophilic surfaces such as
      SiO(2). Pretreatment of surfaces with casein has become the standard protocol for
      achieving optimal kinesin activity, but the mechanism by which casein enhances
      kinesin surface adsorption and function is poorly understood. We used quartz
      crystal microbalance measurements and microtubule gliding assays to uncover the
      role that casein plays in enhancing the activity of surface-adsorbed kinesin. On
      SiO(2) surfaces, casein adsorbs as both a tightly bound monolayer and a
      reversibly bound second layer that has a dissociation constant of 500 nM and can
      be desorbed by washing with casein-free buffer. Experiments using truncated
      kinesins demonstrate that in the presence of soluble casein, kinesin tails bind
      well to the surface, whereas kinesin head binding is blocked. Removing soluble
      casein reverses these binding profiles. Surprisingly, reversibly bound casein
      plays only a moderate role during kinesin adsorption, but it significantly
      enhances kinesin activity when surface-adsorbed motors are interacting with
      microtubules. These results point to a model in which a dynamic casein bilayer
      prevents reversible association of the heads with the surface and enhances
      association of the kinesin tail with the surface. Understanding protein-surface
      interactions in this model system should provide a framework for engineering
      surfaces for functional adsorption of other motor proteins and surface-active
      enzymes.

PMID- 19383475
TI  - Synthetic lipid vesicles recruit native-like aggregates and affect the
      aggregation process of the prion Ure2p: insights on vesicle permeabilization and
      charge selectivity.
AB  - The yeast prion Ure2p polymerizes into native-like fibrils, retaining the overall
      structure and binding properties of the soluble protein. Recently we have shown
      that, similar to amyloid oligomers, the native-like Ure2p fibrils and their
      precursor oligomers are highly toxic to cultured mammalian cells when added to
      the culture medium, whereas Ure2p amyloid fibrils generated by heating the native
      like fibrils are substantially harmless. We show here that, contrary to the
      nontoxic amyloid fibrils, the toxic, native-like Ure2p assemblies induce a
      significant calcein release from negatively charged phosphatidylserine vesicles.
      A minor and less-specific effect was observed with zwitterionic
      phosphatidylcholine vesicles, suggesting that the toxic aggregates preferentially
      bind to negatively charged sites on lipid membranes. We also found that
      cholesterol-enriched phospholipid membranes are protected against
      permeabilization by native-like Ure2p assemblies. Moreover, vesicle
      permeabilization appears charge-selective, allowing calcium, but not chloride,
      influx to be monitored. Finally, we found that the interaction with
      phosphatidylserine membranes speeds up Ure2p polymerization into oligomers and
      fibrils structurally and morphologically similar to the native-like Ure2p
      assemblies arising in free solution, although less cytotoxic. These data suggest
      that soluble Ure2p oligomers and native-like fibrils, but not amyloid fibrils,
      interact intimately with negatively charged lipid membranes, where they allow
      selective cation influx.

PMID- 19383476
TI  - Bovine insulin filaments induced by reducing disulfide bonds show a different
      morphology, secondary structure, and cell toxicity from intact insulin amyloid
      fibrils.
AB  - Amyloid fibrils are associated with more than 20 diseases, including Alzheimer's
      disease and type II diabetes. Insulin is a 51-residue polypeptide hormone, with
      its two polypeptide chains linked by one intrachain and two interchain disulfide
      bonds, and has long been known to self-assemble in vitro into amyloid fibrils. We
      demonstrate here that bovine insulin forms flexible filaments in the presence of
      a reducing agent, Tris (2-carboxyethyl) phosphine. The insulin filaments,
      possibly formed due to partial reduction of S-S bonds in insulin molecules,
      differ from intact insulin fibrils in terms of their secondary structure. The
      insulin filaments were determined to have an antiparallel beta-sheet structure,
      whereas the insulin fibrils have a parallel beta-sheet structure. Of importance,
      the cell toxicity of the insulin filaments was remarkably lower than that of the
      insulin fibrils. This finding supports the idea that cell toxicity of amyloids
      correlates with their morphology. The remarkably low toxicity of the filamentous
      structure should shed new light on possible pharmacological approaches to the
      various diseases caused by amyloid fibrils.

PMID- 19383478
TI  - EPR of Cu2+ prion protein constructs at 2 GHz using the g(perpendicular) region
      to characterize nitrogen ligation.
AB  - A double octarepeat prion protein construct, which has two histidines, mixed with
      copper sulfate in a 3:2 molar ratio provides at most three imidazole ligands to
      each copper ion to form a square-planar Cu(2+) complex. This work is concerned
      with identification of the fourth ligand. A new (to our knowledge) electron
      paramagnetic resonance method based on analysis of the intense features of the
      electron paramagnetic resonance spectrum in the g( perpendicular) region at 2 GHz
      is introduced to distinguish between three and four nitrogen ligands. The
      methodology was established by studies of a model system consisting of histidine
      imidazole ligation to Cu(2+). In this spectral region at 2 GHz (S-band), g-strain
      and broadening from the possible rhombic character of the Zeeman interaction are
      small. The most intense line is identified with the M(I) = +1/2 extra absorption
      peak. Spectral simulation demonstrated that this peak is insensitive to cupric
      A(x) and A(y) hyperfine interaction. The spectral region to the high-field side
      of this peak is uncluttered and suitable for analysis of nitrogen superhyperfine
      couplings to determine the number of nitrogens. The spectral region to the low
      field side of the intense extra absorption peak in the g( perpendicular) part of
      the spectrum is sensitive to the rhombic distortion parameters A(x) and A(y).
      Application of the method to the prion protein system indicates that two species
      are present and that the dominant species contains four nitrogen ligands. A new
      loop-gap microwave resonator is described that contains approximately 1 mL of
      frozen sample.

PMID- 19383477
TI  - Obstacles on the microtubule reduce the processivity of Kinesin-1 in a minimal in
      vitro system and in cell extract.
AB  - Inside cells, a multitude of molecular motors and other microtubule-associated
      proteins are expected to compete for binding to a limited number of binding sites
      available on microtubules. Little is known about how competition for binding
      sites affects the processivity of molecular motors and, therefore, cargo
      transport, organelle positioning, and microtubule organization, processes that
      all depend on the activity of more or less processive motors. Very few studies
      have been performed in the past to address this question directly. Most studies
      reported only minor effects of crowding on the velocity of motors. However, a
      controversy appears to exist regarding the effect of crowding on motor
      processivity. Here, we use single-molecule imaging of mGFP-labeled minimal
      dimeric kinesin-1 constructs in vitro to study the effects of competition on
      kinesin's processivity. For competitors, we use kinesin rigor mutants as static
      roadblocks, minimal wild-type kinesins as motile obstacles, and a cell extract as
      a complex mixture of microtubule-associated proteins. We find that mGFP-labeled
      kinesin-1 detaches prematurely from microtubules when it encounters obstacles,
      leading to a strong reduction of its processivity, a behavior that is largely
      independent of the type of obstacle used here. Kinesin has a low probability to
      wait briefly when encountering roadblocks. Our data suggest, furthermore, that
      kinesin can occasionally pass obstacles on the protofilament track.

PMID- 19383479
TI  - Histone octamer helical tubes suggest that an internucleosomal four-helix bundle
      stabilizes the chromatin fiber.
AB  - A major question in chromatin involves the exact organization of nucleosomes
      within the 30-nm chromatin fiber and its structural determinants of assembly.
      Here we investigate the structure of histone octamer helical tubes via the method
      of iterative helical real-space reconstruction. Accurate placement of the x-ray
      structure of the histone octamer within the reconstructed density yields a
      pseudoatomic model for the entire helix, and allows precise identification of
      molecular interactions between neighboring octamers. One such interaction that
      would not be obscured by DNA in the nucleosome consists of a twofold symmetric
      four-helix bundle formed between pairs of H2B-alpha3 and H2B-alphaC helices of
      neighboring octamers. We believe that this interface can act as an
      internucleosomal four-helix bundle within the context of the chromatin fiber. The
      potential relevance of this interface in the folding of the 30-nm chromatin fiber
      is discussed.

PMID- 19383480
TI  - The mineral phase of calcified cartilage: its molecular structure and interface
      with the organic matrix.
AB  - We have studied the atomic level structure of mineralized articular cartilage
      with heteronuclear solid-state NMR, our aims being to identify the inorganic
      species present at the surfaces of the mineral crystals which may interact with
      the surrounding organic matrix and to determine which components of the organic
      matrix are most closely involved with the mineral crystals. One-dimensional (1)H
      and (31)P and two-dimensional (1)H-(31)P heteronuclear correlation NMR
      experiments show that the mineral component is very similar to that in bone with
      regard to its surface structure. (13)C{(31)P} rotational echo double resonance
      experiments identify the organic molecules at the mineral surface as
      glycosaminoglycans, which concurs with our recent finding in bone. There is also
      evidence of gamma-carboxyglutamic acid residues interacting with the mineral.
      However, other matrix components appear more distant from the mineral compared
      with bone. This may be due to a larger hydration layer on the mineral crystal
      surfaces in calcified cartilage.

PMID- 19383481
TI  - Segmentation of fluorescence microscopy images for quantitative analysis of cell
      nuclear architecture.
AB  - Considerable advances in microscopy, biophysics, and cell biology have provided a
      wealth of imaging data describing the functional organization of the cell
      nucleus. Until recently, cell nuclear architecture has largely been assessed by
      subjective visual inspection of fluorescently labeled components imaged by the
      optical microscope. This approach is inadequate to fully quantify spatial
      associations, especially when the patterns are indistinct, irregular, or highly
      punctate. Accurate image processing techniques as well as statistical and
      computational tools are thus necessary to interpret this data if meaningful
      spatial-function relationships are to be established. Here, we have developed a
      thresholding algorithm, stable count thresholding (SCT), to segment nuclear
      compartments in confocal laser scanning microscopy image stacks to facilitate
      objective and quantitative analysis of the three-dimensional organization of
      these objects using formal statistical methods. We validate the efficacy and
      performance of the SCT algorithm using real images of immunofluorescently stained
      nuclear compartments and fluorescent beads as well as simulated images. In all
      three cases, the SCT algorithm delivers a segmentation that is far better than
      standard thresholding methods, and more importantly, is comparable to manual
      thresholding results. By applying the SCT algorithm and statistical analysis, we
      quantify the spatial configuration of promyelocytic leukemia nuclear bodies with
      respect to irregular-shaped SC35 domains. We show that the compartments are
      closer than expected under a null model for their spatial point distribution, and
      furthermore that their spatial association varies according to cell state. The
      methods reported are general and can readily be applied to quantify the spatial
      interactions of other nuclear compartments.

PMID- 19383482
TI  - Ultramicroscopy reveals axonal transport impairments in cortical motor neurons at
      prion disease.
AB  - The functional imaging of neuronal circuits of the central nervous system is
      crucial for phenotype screenings or investigations of defects in
      neurodegenerative disorders. Current techniques yield either low penetration
      depth, yield poor resolution, or are restricted by the age of the animals. Here,
      we present a novel ultramicroscopy protocol for fluorescence imaging and three
      dimensional reconstruction in the central nervous system of adult mice. In
      combination with tracing as a functional assay for axonal transport, retrogradely
      labeled descending motor neurons were visualized with >4 mm penetration depth.
      The analysis of the motor cortex shortly before the onset of clinical prion
      disease revealed that >80% neurons have functional impairments in axonal
      transport. Our study provides evidence that prion disease is associated with
      severe axonal transport defects in the cortical motor neurons and suggests a
      novel mechanism for prion-mediated neurodegeneration.

PMID- 19383483
TI  - Assigning membrane binding geometry of cytochrome C by polarized light
      spectroscopy.
AB  - In this work we demonstrate how polarized light absorption spectroscopy (linear
      dichroism (LD)) analysis of the peptide ultraviolet-visible spectrum of a
      membrane-associated protein (cytochrome (cyt) c) allows orientation and structure
      to be assessed with quite high accuracy in a native membrane environment that can
      be systematically varied with respect to lipid composition. Cyt c binds strongly
      to negatively charged lipid bilayers with a distinct orientation in which its
      alpha-helical segments are on average parallel to the membrane surface. Further
      information is provided by the LD of the pi-pi( *) transitions of the heme
      porphyrin and transitions of aromatic residues, mainly a single tryptophan. A
      good correlation with NMR data was found, and combining NMR structural data with
      LD angular data allowed the whole protein to be docked to the lipid membrane.
      When the redox state of cyt c was changed, distinct variations in the LD spectrum
      of the heme Soret band were seen corresponding to changes in electronic
      transition energies; however, no significant change in the overall protein
      orientation or structure was observed. Cyt c is known to interact in a specific
      manner with the doubly negatively charged lipid cardiolipin, and incorporation of
      this lipid into the membrane at physiologically relevant levels was indeed found
      to affect the protein orientation and its alpha-helical content. The detail in
      which cyt c binding is described in this study shows the potential of LD
      spectroscopy using shear-deformed lipid vesicles as a new methodology for
      exploring membrane protein structure and orientation.

PMID- 19383484
TI  - Association kinetics from single molecule force spectroscopy measurements.
AB  - Single molecule force spectroscopy is often used to study the dissociation of
      single molecules by applying mechanical force to the intermolecular bond. These
      measurements provide the kinetic parameters of dissociation. We present what to
      our knowledge is a new atomic force microscopy-based approach to obtain the
      activation energy of the association reaction and approximate grafting density of
      reactive receptors using the dependence of the probability to form molecular
      bonds on probe velocity when one of the interacting molecules is tethered by a
      flexible polymeric linker to the atomic force microscopy probe. Possible errors
      in the activation energy measured with this approach are considered and resulting
      corrections are included in the data analysis. This new approach uses the same
      experimental setup as traditional force spectroscopy measurements that quantify
      dissociation kinetics. We apply the developed methodology to measure the
      activation energy of biotin-streptavidin association (including a contribution
      from the steric factor) and obtain a value of 8 +/- 1 kT. This value is
      consistent with the association rate measured previously in solution. Comparison
      with the solution-derived activation energy indicates that kinetics of biotin
      streptavidin binding is mainly controlled by the reaction step.

PMID- 19383485
TI  - Cell-shape regulation of smooth muscle cell proliferation.
AB  - Vascular smooth muscle cells (SMCs) play an important role in vascular
      remodeling. Heterogeneity and phenotypic changes in SMCs are usually accompanied
      by a morphological difference, i.e., elongated/spindle-like versus spread-out or
      epithelioid/rhomboid cell shapes. However, it is not known whether the cell shape
      directly regulates SMC proliferation, and what the underlying mechanisms are. In
      this study, microgrooves and micropatterned matrix islands were used to engineer
      the cell shape and investigate the associated biophysical and biological
      mechanisms. Compared to spread-out SMCs on nonpatterned surfaces, SMCs on
      micropatterned surfaces demonstrated elongated morphology, significantly lower
      cell and nucleus shape indexes, less spreading, a lower proliferation rate, and a
      similar response (but to a lesser extent) to platelet-derived growth factor,
      transforming growth factor-beta, and mechanical stretching. DNA microarray
      profiling revealed a lower expression of neuron-derived orphan receptor-1 (NOR-1)
      in elongated SMCs. Knocking down NOR-1 suppressed DNA synthesis in SMCs,
      suggesting that NOR-1 is a mediator of cell elongation effects. Regulation of DNA
      synthesis in SMCs by the cell shape alone and a decrease in DNA synthesis in the
      case of small cell spreading area were achieved by micropatterning SMCs on matrix
      islands of different shapes and spreading areas. Changes in the cell shape also
      affected the nucleus shape, whereas variations in the cell spreading area
      modulated the nucleus volume, indicating a possible link between nucleus
      morphology (both shape and volume) and DNA synthesis. The findings of this
      investigation provide insight into cell shape effects on cell structure and
      proliferation, and have direct implications for vascular pathophysiology.

PMID- 19383486
TI  - Structural changes in the catalytic cycle of the Na+,K+-ATPase studied by
      infrared spectroscopy.
AB  - Pig kidney Na(+),K(+)-ATPase was studied by means of reaction-induced infrared
      difference spectroscopy. The reaction from E1Na(3)(+) to an E2P state was
      initiated by photolysis of P(3)-1-(2-nitrophenyl)ethyl ATP (NPE caged ATP) in
      samples that contained 3 mM free Mg(2+) and 130 mM NaCl at pH 7.5. Release of ATP
      from caged ATP produced highly detailed infrared difference spectra indicating
      structural changes of the Na(+),K(+)-ATPase. The observed transient state of the
      enzyme accumulated within seconds after ATP release and decayed on a timescale of
      minutes at 15 degrees C. Several controls ensured that the observed difference
      signals were due to structural changes of the Na(+),K(+)-ATPase. Samples that
      additionally contained 20 mM KCl showed similar spectra but less intense
      difference bands. The absorbance changes observed in the amide I region,
      reflecting conformational changes of the protein backbone, corresponded to only
      0.3% of the maximum absorbance. Thus the net change of secondary structure was
      concluded to be very small, which is in line with movement of rigid protein
      segments during the catalytic cycle. Despite their small amplitude, the amide I
      signals unambiguously reveal the involvement of several secondary structure
      elements in the conformational change. Similarities and dissimilarities to
      corresponding spectra of the Ca(2+)-ATPase and H(+),K(+)-ATPase are discussed,
      and suggest characteristic bands for the E1 and E2 conformations at 1641 and 1661
      cm(-1), respectively, for alphabeta heterodimeric ATPases. The spectra further
      indicate the participation of protonated carboxyl groups or lipid carbonyl groups
      in the reaction from E1Na(3)(+) to an E2P state. A negative band at 1730 cm(-1)
      is in line with the presence of a protonated Asp or Glu residue that coordinates
      Na(+) in E1Na(3)(+). Infrared signals were also detected in the absorption
      regions of ionized carboxyl groups.

PMID- 19383487
TI  - Latency-related development of functional connections in cultured cortical
      networks.
AB  - To study plasticity, we cultured cortical networks on multielectrode arrays,
      enabling simultaneous recording from multiple neurons. We used conditional firing
      probabilities to describe functional network connections by their strength and
      latency. These are abstract representations of neuronal pathways and may arise
      from direct pathways between two neurons or from a common input. Functional
      connections based on direct pathways should reflect synaptic properties.
      Therefore, we searched for long-term potentiation (this mechanism occurs in vivo
      when presynaptic action potentials precede postsynaptic ones with interspike
      intervals up to approximately 20 ms) in vitro. To investigate if the strength of
      functional connections showed a similar latency-related development, we selected
      periods of monotonously increasing or decreasing strength. We observed increased
      incidence of short latencies (5-30 ms) during strengthening, whereas these rarely
      occurred during weakening. Furthermore, we saw an increased incidence of 40-65 ms
      latencies during weakening. Conversely, functional connections tended to
      strengthen in periods with short latency, whereas strengthening was significantly
      less than average during long latency. Our data suggest that functional
      connections contain information about synaptic connections, that conditional
      firing probability analysis is sensitive enough to detect it and that a
      substantial fraction of all functional connections is based on direct pathways.

PMID- 19383488
TI  - Magnetic compass of birds is based on a molecule with optimal directional
      sensitivity.
AB  - The avian magnetic compass has been well characterized in behavioral tests: it is
      an "inclination compass" based on the inclination of the field lines rather than
      on the polarity, and its operation requires short-wavelength light. The "radical
      pair" model suggests that these properties reflect the use of specialized
      photopigments in the primary process of magnetoreception; it has recently been
      supported by experimental evidence indicating a role of magnetically sensitive
      radical-pair processes in the avian magnetic compass. In a multidisciplinary
      approach subjecting migratory birds to oscillating fields and using their
      orientation responses as a criterion for unhindered magnetoreception, we identify
      key features of the underlying receptor molecules. Our observation of resonance
      effects at specific frequencies, combined with new theoretical considerations and
      calculations, indicate that birds use a radical pair with special properties that
      is optimally designed as a receptor in a biological compass. This radical pair
      design might be realized by cryptochrome photoreceptors if paired with molecular
      oxygen as a reaction partner.

PMID- 19383489
TI  - Ca(2+)-induced stimulation of the membrane binding of Escherichia coli SecA and
      its association with signal peptides of secretory proteins.
AB  - Previously, it was found that Ca(2+) stimulates the intrinsic Escherichia coli
      SecA ATPase activity [Kim et al., FEBS Lett. 493 (2001) 12-16]. Now, we suggest
      that Ca(2+) is required for efficient interaction of SecA with membranes and the
      signal peptide of ribose-binding protein. When the amount of external Ca(2+) was
      enhanced, the amounts of membrane-bound SecA and its lipid/ATPase activity
      increased. In the presence of entrapped Ca(2+) in liposomes, the binding was also
      stimulated in a Ca(2+) concentration-dependent manner. The effect of Ca(2+) on
      the functional regulation of SecA was also evident in the presence of the signal
      peptides of secretory proteins, which the interaction of SecA with the signal
      peptide increased with increasing Ca(2+) concentration in the presence of
      membranes. However, other divalent cations including Mg(2+), Mn(2+), and Zn(2+)
      had inhibitory or no effect, suggesting a specific role of Ca(2+) in SecA
      interaction with lipid bilayers and signal peptides.

PMID- 19383490
TI  - Thermal stability and redox properties of M. tuberculosis CuSOD.
AB  - The superoxide dismutase from Mycobacterium tuberculosis is the only Cu
      containing superoxide dismutase that lacks zinc in the active site. To explore
      the structural properties of this unusual enzyme, we have investigated its
      stability by differential scanning calorimetry. We have found that the holo
      enzyme is significantly more stable than the apo-protein or the partially
      metallated enzyme, but that its melting temperature is markedly lower than that
      of all the other characterized eukaryotic and prokaryotic Cu,Zn superoxide
      dismutases. We have also observed that, unlike the zinc-free eukaryotic or
      bacterial enzymes, the active site copper of the mycobacterial enzyme is not
      reduced by ascorbate, confirming that its redox properties are comparable to
      those typical of the enzymes containing zinc in the active site. Our findings
      highlight the role of zinc in conferring stability to Cu,Zn superoxide dismutases
      and indicate that the structural rearrangements observed in M. tuberculosis
      Cu,SOD compensate for the absence of zinc in achieving a fully active enzyme.

PMID- 19383491
TI  - PPARgamma transcriptionally regulates the expression of insulin-degrading enzyme
      in primary neurons.
AB  - Insulin-degrading enzyme (IDE) is a protease that has been demonstrated to play a
      key role in degrading both Abeta and insulin and deficient in IDE function is
      associated with Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2)
      pathology. However, little is known about the cellular and molecular regulation
      of IDE expression. Here we show IDE levels are markedly decreased in DM2 patients
      and positively correlated with the peroxisome proliferator-activated receptor
      gamma (PPARgamma) levels. Further studies show that PPARgamma plays an important
      role in regulating IDE expression in rat primary neurons through binding to a
      functional peroxisome proliferator-response element (PPRE) in IDE promoter and
      promoting IDE gene transcription. Finally, we demonstrate that PPARgamma
      participates in the insulin-induced IDE expression in neurons. These results
      suggest that PPARgamma transcriptionally induces IDE expression which provides a
      novel mechanism for the use of PPARgamma agonists in both DM2 and AD therapies.

PMID- 19383492
TI  - Study on the levels of trace elements in mild and severe psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic, recurrent skin disorder characterized
      histologically by cutaneous inflammation, increased epidermal proliferation,
      hyperkeratosis, angiogenesis, abnormal keratinization, shortened maturation time
      and parakeratosis. Data on the involvement of trace elements in the pathogenesis
      of psoriasis is limited. METHODS: The elements namely Na, K, Ca, P, S, Mg, Cu,
      Zn, and Fe were analyzed in the serum samples of mild and severe psoriasis
      patients with a control group using inductively coupled plasma-atomic emission
      spectroscopy (ICP-AES). Patients were assessed as per standard clinical
      diagnostic criteria and classified into mild and severe psoriasis groups using
      Psoriasis Area Severity Index (PASI) score. RESULTS: In mild psoriasis, the
      levels of K, P, Cu, and Mg were increased significantly (p<0.001), while in
      severe psoriasis P, Mg, and Cu were increased significantly (p<0.001). The S and
      Fe concentrations were decreased significantly (p<0.001) in both mild and severe
      psoriasis types when compared to control. CONCLUSIONS: There is a disturbance in
      the under-study element contents and also element-element interdependency in
      psoriasis serum when compared to controls.

PMID- 19383493
TI  - Profile of the new pyrrolidone derivative seletracetam (ucb 44212) in animal
      models of epilepsy.
AB  - Seletracetam is a pyrrolidone derivative with a one-log-unit higher affinity for
      the synaptic vesicle protein 2A (SV2A) than levetiracetam (Keppra). This study
      explored its anticonvulsant properties in animal models of epilepsy. Seletracetam
      reduced both the amplitude and repetitive firing of population spikes induced by
      a high K(+)/low Ca(2+) concentration fluid (HKLCF) in rat hippocampal slices. The
      reduction of HKLCF-induced increases in population spike amplitude was
      particularly pronounced, and occurred at approximately 10 times lower
      seletracetam concentrations than previously observed for levetiracetam. These
      invitro data suggest that desynchronisation of epileptiform activity may
      contribute significantly to the antiepileptic properties of seletracetam.
      Seletracetam also showed a potent anti-seizure activity in animal models
      mimicking partial-onset (kindled animals) and generalized epilepsy (audiogenic
      seizure susceptible mice and genetic absence epilepsy rats from Strasbourg
      (GAERS)). In amygdala-kindled rats, seletracetam increased the generalized
      seizure threshold current and decreased the duration of the after-discharge and
      the seizure severity observed at the after-discharge threshold current, and
      generally had a much more potent effect than previously observed for
      levetiracetam. Seletracetam showed no psychomimetic effects and a very high
      central nervous system (CNS) tolerability in both kindled and GAERS rats,
      markedly superior to that of levetiracetam and other antiepileptic drugs. These
      results suggest that seletracetam may represent an effective and very well
      tolerated broad-spectrum agent for the symptomatic treatment of epilepsy.

PMID- 19383494
TI  - Effects of cytokines on mechanical and epithelial bioelectric responses to
      methacholine and hyperosmolarity in guinea-pig airways: an in vitro study.
AB  - We observed previously that lipopolysaccharide (LPS) 18 h after i.p. injection of
      guinea pigs increased transepithelial potential difference (V(t)),
      hyperpolarization responses to methacholine, and hyperosmolarity-induced,
      epithelium-derived relaxing factor (EpDRF)-mediated relaxation responses, in
      excised and perfused tracheal segments. To investigate their roles in these
      changes, the effects of cytokines on in vitro epithelial bioelectric and smooth
      muscle mechanical responses were investigated using the isolated, perfused
      trachea preparation. Tracheas were incubated (6 h) with LPS or IL-1beta, IL-4, IL
      13, IFN-gamma, TNF-alpha, singly or in combination. Incubation with LPS and
      cytomix (IL-1beta+IFN-gamma+TNF-alpha together) had no effect on muscle
      reactivity to methacholine, but potentiated D-mannitol-induced relaxation.
      Individually, IL-1beta and IFN-gamma inhibited methacholine-induced contractions
      and potentiated D-mannitol-induced relaxation responses. TNF-alpha increased
      contractions to methacholine but had no effect on relaxation responses to D
      mannitol. Methacholine elicited hyperpolarization in low concentrations and
      depolarization in high concentrations. The individual cytokines decreased the
      hyperpolarization response to low methacholine concentrations and increased the
      depolarization response to high methacholine concentrations but had no effect on
      V(t) responses to D-mannitol. Cytomix did not affect V(t) responses to
      methacholine, but potentiated both the hyperpolarization and depolarization
      responses to D-mannitol. In Ussing chambers all agents except IL-1beta and IFN
      gamma increased V(t); IL-1beta decreased slightly but none of the other agents
      affected transepithelial resistance (R(t)). The results indicate that cytokines
      and LPS alter smooth muscle reactivity to methacholine, potentiate EpDRF-mediated
      relaxation responses and, thereby, mimic the effects of LPS treatment in vivo,
      but do not recapitulate LPS' effects on V(t) responses.

PMID- 19383495
TI  - Effects of the non-peptidyl low molecular weight radical scavenger IAC in DNBS
      induced colitis in rats.
AB  - Intestinal inflammation is accompanied by excessive production of reactive oxygen
      and nitrogen radical species because of the massive infiltration of
      polymorphonuclear and mononuclear leukocytes. Antioxidant compounds seem to
      protect against experimental colitis. Here we investigated the effects of the
      innovative non-peptidyl, low molecular weight radical scavenger bis(1-hydroxy
      2,2,6,6-tetramethyl-4-piperidinyl)decandioate (IAC), which is highly reactive
      with most oxygen, nitrogen and carbon centred radicals and is easily distributed
      in cell membranes and intra-extra cellular compartments, in the DNBS model of
      colitis. Colitis was induced in male SD rats by intrarectal administration of
      DNBS (15 mg/rat). IAC (30 mg/kg b.w., hydrophilic or lipophilic form) was
      administered daily (orally or i.p.) starting from the day before the induction of
      colitis for 7 days (n=6-8 per group). Colonic damage was assessed by means of
      macroscopic and histological scores, myeloperoxidase activity (MPO) and TNF-alpha
      tissue levels. Colitis impaired body weight gain and markedly increased all
      inflammatory parameters. IAC significantly counteracted the reduction in body
      weight gain, decreased colonic damage and inflammation and TNF-alpha levels in
      DNBS-colitis. The antioxidant IAC significantly ameliorates experimental colitis
      in rats. This strengthens the notion that antioxidant compounds may have
      therapeutic potential in inflammatory bowel disease.

PMID- 19383496
TI  - Methotrexate induces apoptosis in CaSki and NRK cells and influences the
      organization of their actin cytoskeleton.
AB  - Methotrexate is a widely used drug in treatments of various types of malignancies
      and in the therapy of rheumatoid arthritis. The goal of our study was to look at
      the effect of this dihydrofolate reductase inhibitor on the actin cytoskeleton,
      since actin plays an important role in cancer transformation and metastasis. For
      this reason we compared results obtained from experiments on CaSki (human uterine
      cervix cancer) and NRK (normal fibroblastic rat kidney) cells treated with
      methotrexate. It has been shown previously that methotrexate can induce
      apoptosis. Therefore we first examined whether methotrexate induces apoptosis in
      our model cells. For this aim we applied several assays like Caspase Glo 3/7, DNA
      fragmentation and binding of phosphatidylserine by annexin V-fluorescein. The
      data obtained indicated that methotrexate induces programmed cell death in CaSki
      and NRK cells. However, differences between CaSki and NRK cells were observed in
      the morphological alterations and dynamics of apoptosis induced by methotrexate.
      It seemed that cancer cells were more sensitive towards the cell death inducing
      activity at lower concentrations of methotrexate. Analysis by confocal microscopy
      of methotrexate-treated cells demonstrated that treatment with this folate
      antagonist affected the actin cytoskeleton, although the dis-organization of the
      actin cytoskeleton after treatment with methotrexate differed between cancer and
      normal cells.

PMID- 19383497
TI  - IL-6-trans-signalling increases rapid-eye-movement sleep in rats.
AB  - Interleukin 6 (IL-6), a cytokine of the gp130-signalling-family, plays an
      important role in immediate immunological functions, in metabolism and in the
      central nervous system. IL-6-signalling is mediated by classic-signalling via the
      membrane bound IL-6 receptor or by IL-6-trans-signalling via the soluble IL-6
      receptor. Whereas the receptor subunit gp130 is ubiquitously expressed within the
      body, IL-6 receptor expression is restricted to distinct cell populations. Within
      the brain parenchyma the IL-6 receptor is sparsely expressed, and therefore the
      brain is mostly dependent on IL-6-trans-signalling in its response to IL-6.
      Recently we have shown that IL-6-trans-signalling but not classic-signalling
      plays a pivotal role in the establishment and maintenance of chronic inflammation
      and cancer, whereas its role in sleep regulation has not been studied so far. We
      reasoned that the IL-6-trans-signalling mimetic Hyper-IL-6 which in contrast to
      IL-6 alone can activate almost all cells of the brain might have a profound
      effect on sleep regulation and performed sleep recordings with rats injected with
      recombinant Hyper-IL-6. In the present study, the i.c.v. administration of the
      designer cytokine Hyper-IL-6 into rats at dark onset increased the amount of
      rapid-eye-movement sleep (REM sleep) but did not affect non-rapid-eye-movement
      sleep (non-REM sleep). Our data define a new role of IL-6-trans-signalling in
      sleep regulation.

PMID- 19383498
TI  - Pleiotropic functional effects of the first epilepsy-associated mutation in the
      human CHRNA2 gene.
AB  - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) can be caused by
      mutations in the neuronal nicotinic acetylcholine receptor (nAChR) subunit genes
      CHRNA4 and CHRNB2. Recently, a point mutation (alpha2-I279N) associated with
      sleep-related epilepsy has been described in a third nAChR gene, CHRNA2. We
      demonstrate here that alpha2-I279N can be co-expressed with the major structural
      subunit CHRNB2. alpha2-I279N causes a marked gain-of-function effect and displays
      a distinct biopharmacological profile, including markedly reduced inhibition by
      carbamazepine and increased nicotine sensitivity.

PMID- 19383499
TI  - A crtA-related gene from Flavobacterium P99-3 encodes a novel carotenoid 2
      hydroxylase involved in myxol biosynthesis.
AB  - A genomic DNA fragment with carotenogenic genes involved in myxol biosynthesis
      (3',4'-didehydro-1',2'-dihydro-beta,psi-carotene-3,1',2'-triol) was cloned from
      Flavobacterium P99-3. It contains a gene highly homologous to crtA from purple
      bacteria encoding there an acyclic carotenoid 2-ketolase. Since no ketolation
      step is involved in myxol biosynthesis, the function of crtA-OH from
      Flavobacterium was assigned by complementation in Escherichia coli engineered to
      synthesize demethylspheroidene and 1'-hydroxy-demethylspheroidene. Upon co
      expression of crtA-OH, the formation of 2-hydroxy derivatives of both carotenoids
      assigns CrtA-OH as a novel carotenoid hydroxylase. The gene was used to re
      construct myxol biosynthesis in E. coli successfully. Additionally, 1',2'
      dihydroxytorulene and 1,2,1'-trihydroxy-3,4,3',4'-tetradehydrolycopene were
      obtained. Their generation demonstrates that a new class of 2-hydroxy carotenoids
      can now be pursued by genetic engineering in E. coli.

PMID- 19383500
TI  - Towards mimicking natural protein channels with aligned carbon nanotube membranes
      for active drug delivery.
AB  - AIMS: Carbon nanotube (CNT) membranes offer an exciting opportunity to mimic
      natural protein channels due to 1) a mechanism of dramatically enhanced fluid
      flow 2) ability to place 'gatekeeper' chemistry at the entrance to pores 3) the
      ability for biochemical reactions to occur on gatekeeper molecules and 4) an
      ability to chemically functionalize each side of the membrane independently. MAIN
      METHODS: Aligned CNT membranes were fabricated and CNT pore entrances modified
      with gatekeeper chemistry. Pressure driven fluid flow and diffusion experiments
      were performed to study the mechanisms of transport through CNTs. KEY FINDINGS:
      The transport mechanism through CNT membranes is primarily 1) ionic diffusion
      near bulk expectation 2) gas flow enhanced 1-2 orders of magnitude primarily due
      to specular reflection 3) fluid flow 4-5 orders of magnitude faster than
      conventional materials due to a nearly ideal slip-boundary interface. The
      transport can be modulated by 'gatekeeper' chemistry at the pore entrance using
      steric hindrance, electrostatic attraction/repulsion, or biochemical state. The
      conformation of charged tethered molecules can be modulated by applied bias
      setting the stage for programmable drug release devices. SIGNIFICANCE: The
      membrane structure is mechanically far more robust than lipid bilayer films,
      allowing for large-scale chemical separations, delivery or sensing based on the
      principles of protein channels. The performance of protein channels is several
      orders of magnitude faster than conventional membrane materials. The fundamental
      requirements of mimicking protein channels are present in the CNT membrane
      system.

PMID- 19383501
TI  - Behavioral correlates of corpus callosum size: anatomical/behavioral
      relationships vary across sex/handedness groups.
AB  - There are substantial individual differences in the size and shape of the corpus
      callosum and such differences are thought to relate to behavioral lateralization.
      We report findings from a large scale investigation of relationships between
      brain anatomy and behavioral asymmetry on a battery of visual word recognition
      tasks. A sample of 200 individuals was divided into groups on the basis of sex
      and consistency of handedness. We investigated differences between sex/handedness
      groups in callosal area and relationships between callosal area and behavioral
      predictors. Sex/handedness groups did not show systematic differences in callosal
      area or behavioral asymmetry. However, the groups differed in the relationships
      between area of the corpus callosum and behavioral asymmetry. Among consistent
      handed males, callosal area was negatively related to behavioral laterality.
      Among mixed-handed males and consistent-handed females, behavioral laterality was
      not predictive of callosal area. The most robust relationship was observed in
      mixed-handed females, in whom behavioral asymmetry was positively related to
      callosal area. Our study demonstrates the importance of considering
      brain/behavior relationships within sub-populations, as relationships between
      behavioral asymmetry and callosal anatomy varied across subject groups.

PMID- 19383502
TI  - Different behavioral and eye movement patterns of dyslexic readers with and
      without attentional deficits during single word reading.
AB  - Comorbidity of learning disabilities is a very common phenomenon which is
      intensively studied in genetics, neuropsychology, prevalence studies and causal
      deficit research. In studies on the behavioral manifestation of learning
      disabilities, however, comorbidity is often neglected. In the present study, we
      systematically examined the reading behavior of German-speaking children with
      dyslexia, of children with attentional problems, of children with comorbid
      dyslexia and attentional problems and of normally developing children by
      measuring their reading accuracy, naming latencies and eye movement patterns
      during single word reading. We manipulated word difficulty by contrasting (1)
      short vs. long words with (2) either low or high sublexical complexity (indexed
      by consonant cluster density). Children with dyslexia only (DYS) showed the
      expected reading fluency impairment of poor readers in regular orthographies but
      no accuracy problem. In contrast, comorbid children (DYS+AD) had significantly
      higher error rates than all other groups, but less of a problem with reading
      fluency than DYS. Concurrently recorded eye movement measures revealed that DYS
      made the highest number of fixations, but exhibited shorter mean single fixations
      than DYS+AD. Word length had the strongest effect on dyslexic children, whereas
      consonant cluster density affected all groups equally. Theoretical implications
      of these behavioral and eye movement patterns are discussed and the necessity for
      controlling for comorbid attentional deficits in children with reading deficits
      is highlighted.

PMID- 19383504
TI  - Comparing a single case with a control sample: refinements and extensions.
AB  - Crawford and Garthwaite [Crawford, J. R. & Garthwaite, P. H. (2002).
      Investigation of the single case in neuropsychology: Confidence limits on the
      abnormality and test score differences. Neuropsychologia, 40, 1196-1208] have
      proposed an adjusted t-test, widely used in experimental neuropsychology, for
      comparing a single case with a control sample. This test does not assess whether
      the single-case score belongs in the population from which the control sample is
      drawn, but rather whether the mean of the distribution from which the case was
      drawn differs significantly from the mean of the control population. This
      approach is readily extended to more complex designs in which the analysis of
      variance is appropriate, and the single case is treated as belonging to a group
      of size one. The main qualification in using either this or Crawford and Howell's
      approach is that it makes the untestable assumption of homogeneity of variance
      between the two populations, but a simple adjustment either to the t-test or to
      the analysis of variance allows one to draw conclusions about the relation of the
      case itself to the control population.

PMID- 19383503
TI  - Right dorsolateral prefrontal cortex is engaged during post-retrieval processing
      of both episodic and semantic information.
AB  - Post-retrieval processes are engaged when the outcome of a retrieval attempt must
      be monitored or evaluated. Functional neuroimaging studies have implicated right
      dorsolateral prefrontal cortex (DLPFC) as playing a role in post-retrieval
      processing. The present study used fMRI to investigate whether retrieval-related
      neural activity in DLPFC is associated specifically with monitoring the episodic
      content of a retrieval attempt. During study, subjects were cued to make one of
      two semantic judgments on serially presented pictures. One study phase was
      followed by a source memory task, in which subjects responded 'new' to unstudied
      pictures, and signaled the semantic judgment made on each studied picture. A
      separate study phase was followed by a task in which the studied items were
      subjected to a judgment about their semantic attributes. Both tasks required that
      retrieved information be evaluated prior to response selection, but only the
      source memory task required evaluation of retrieved episodic information. In both
      tasks, activity in a common region of right DLPFC was greater for studied than
      for unstudied items, and the magnitude of this effect did not differ between the
      tasks. Together with the results of a parallel event-related potential study
      [Hayama, H. R., Johnson, J. D., & Rugg, M. D. (2008). The relationship between
      the right frontal old/new ERP effect and post-retrieval monitoring: Specific or
      non-specific? Neuropsychologia, 46(5), 1211-1223, doi:S0028-3932(07)00390-9], the
      present findings indicate that putative right DLPFC correlates of post-retrieval
      processing are not associated exclusively with monitoring or evaluating episodic
      content. Rather, the effects likely reflect processing associated with monitoring
      or decision-making in multiple cognitive domains.

PMID- 19383505
TI  - On the origin of line bisection error in hemianopia.
AB  - The contralesional line bisection error in hemianopia is a well-known clinical
      phenomenon. Its origin, however, is still unclear. We therefore investigated the
      causes of the hemianopic bisection error in 84 patients with unilateral
      homonymous hemianopia without visuospatial neglect. Our results suggest that the
      contralesional bisection error is neither a consequence of the visual field
      defect itself nor a manifestation of strategic adaptation of attention and eye
      movements into contralesional hemispace. Additional extrastriate brain injury,
      presumably to occipito-temporal areas including the occipital white matter, seems
      to be critical for the emergence of the contralesional bisection error that is
      frequently associated with but separable from homonymous hemianopia.

PMID- 19383506
TI  - On comparing a single case with a control sample: an alternative perspective.
AB  - Corballis [Corballis, M. C. (2009). Comparing a single case with a control
      sample: Refinements and extensions. Neuropsychologia] offers an interesting
      position paper on statistical inference in single-case studies. The following
      points arise: (1) Testing whether we can reject the null hypothesis that a
      patient's score is an observation from the population of control scores can be a
      legitimate aim for single-case researchers, not just clinicians. (2) Counter to
      the claim made by Corballis [Corballis, M. C. (2009). Comparing a single case
      with a control sample: Refinements and extensions. Neuropsychologia], Crawford
      and Howell's [Crawford, J. R., & Howell, D. C. (1998). Comparing an individual's
      test score against norms derived from small samples. The Clinical
      Neuropsychologist, 12, 482-486] method does test whether we can reject the above
      null hypothesis. (3) In all but the most unusual of circumstances Crawford and
      Howell's method can also safely be used to test whether the mean of a notional
      patient population is lower than that of a control population, should
      neuropsychologists wish to construe the test in this way. (4) In contrast, the
      method proposed by Corballis is not legitimate for either of these purposes
      because it fails to allow for uncertainty over the control mean (as a result Type
      I errors will not be under control). (5) The use of a mixed ANOVA design to
      compare a case to controls (with or without the adjustment proposed by Corballis)
      is beset with problems but these can be overcome using alternative methods.

PMID- 19383507
TI  - Comparing a single case with a control sample: correction and further comment.
AB  - Crawford, Garthwaite and Howell [Crawford, J. R., Garthwaite, P. H., & Howell, D.
      C. On comparing a single case with a control sample: An alternative perspective.
      Neuropsychologia, in press] correctly point out that the t-test I suggested for
      asking whether a single case belongs in the population from which a control
      sample is drawn is incorrect. In fact, the corrected formula can be interpreted
      either as addressing this question, or as asking whether the single case and the
      control sample are drawn from populations with the same mean. Extension to
      analysis of variance is recommended for factorial experiments, where single case
      and control sample are tested under different experimental conditions. It is not
      recommended for studies in which different tests are administered and treated as
      different levels of the same dependent variable, as in tests for
      neuropsychological dissociations.

PMID- 19383508
TI  - Karlin volume.

PMID- 19383509
TI  - Chick eyes compensate for chromatic simulations of hyperopic and myopic defocus:
      evidence that the eye uses longitudinal chromatic aberration to guide eye-growth.
AB  - Longitudinal chromatic aberration (LCA) causes short wavelengths to be focused in
      front of long wavelengths. This chromatic signal is evidently used to guide
      ocular accommodation. We asked whether chick eyes exposed to static gratings
      simulating the chromatic effects of myopic or hyperopic defocus would
      "compensate" for the simulated defocus. We alternately exposed one eye of each
      chick to a sine-wave grating (5 or 2 cycle/deg) simulating myopic defocus ("MY
      defocus": image focused in front of retina; hence, red contrast higher than blue)
      and the other eye to a grating of the same spatial frequency simulating hyperopic
      defocus ("HY defocus": blue contrast higher than red). The chicks were placed in
      a drum with one eye covered with one grating, and then switched to another drum
      with the other grating with the other eye covered. To minimize the effects of
      altered eye-growth on image contrast, we studied only the earliest responses:
      first, we measured changes in choroidal thickness 45 min to 1 h after one 15-min
      episode in the drum, then we measured glycosaminoglycans (GAG) synthesis in
      sclera and choroid (by the incorporation of labeled sulfate in tissue culture)
      after a day of four 30-min episodes in the drum. The eyes compensated in the
      appropriate directions: The choroids of the eyes exposed to the HY simulation
      showed significantly more thinning (less thickening) over the course of the
      experiment than the choroids of the eyes exposed to the MY simulation (all groups
      mean:-17 microm; 5 c/d groups: -24 microm; paired t-test (one-tailed): p=0.0006).
      The rate of scleral GAG synthesis in the eye exposed to the HY simulation was
      significantly greater than in the eye exposed to the MY simulation (HY/MY
      ratio=1.20; one sample t-test (one-tailed): p=0.015). There was no significant
      interaction between the sign of the simulated defocus and either the spatial
      frequency or the presence of a +3 D lens used to compensate for the 33 cm
      distance of the drum. Although previous work has shown that chromatic cues to
      defocus are not essential for lens-compensation, in that chicks can compensate in
      monochromatic light, our evidence implies that the eye may be able to infer
      whether the eye is myopic or hyperopic from the different chromatic contrasts
      that result from different signs of defocus.

PMID- 19383510
TI  - Backward masking suppresses collinear facilitation in the visual cortex.
AB  - Perceptual facilitation in detecting low-contrast Gabor patches (GPs) is induced
      by collinearly oriented high-contrast flankers. Our recent Visual Evoked
      Potentials (VEPs) study provided new physiological evidence for these collinear
      interactions, reflected by nonlinear modulation of multiple waveform components
      and frequencies [Sterkin, A., Yehezkel, O., Bonneh, Y. S., Norcia, A., & Polat,
      U. (2008). Multi-component correlate for lateral collinear interactions in the
      human visual cortex. Vision Research, 48(15), 1641-1647]. Here we used VEPs to
      study the temporal structure of this process. Low-contrast, foveal target GP (T)
      was simultaneously flanked by two collinear high-contrast GPs with a spatial
      separation that induces facilitation of T (lateral masking, LM). Another mask,
      identical to LM, was presented at different time-intervals (ISIs) after LM
      (backward masking, BM-on-LM). The responses were compared to separate waveforms
      evoked by T-alone and mask-alone at different ISIs. BM canceled the physiological
      markers of facilitation at an ISI of 50 ms, in agreement with earlier
      psychophysical findings, whereas no BM effect on T-alone was observed. This ISI
      coincides with the active time-window of lateral interactions, confirming our
      working model. The waveform amplitude of the negative N1 peak of LM was modulated
      toward the linear prediction of no interactions and the spectrum was shifted
      toward suppression, with no evidence of facilitation. Moreover, the P1 peak
      amplitude of BM was decreased at the same ISI, indicating that there is a mutual
      interference in cortical representation of both events. Waveform subtraction
      between BM-on-LM and LM suggests a mechanism of extended persistence of the
      target representation underlying facilitation in LM. We suggest an explanation
      for the role of improved detection of collinear stimuli in grouping of contours.

PMID- 19383511
TI  - Sleep spindles and spike-wave discharges in EEG: Their generic features,
      similarities and distinctions disclosed with Fourier transform and continuous
      wavelet analysis.
AB  - Epileptic activity in the form of spike-wave discharges (SWD) appears in the
      electroencephalogram (EEG) during absence seizures. A relationship between SWD
      and normal sleep spindles is often assumed. This study compares time-frequency
      parameters of SWD and sleep spindles as recorded in the EEG in the WAG/Rij rat
      model of absence epilepsy. Fast Fourier transformation and continuous wavelet
      transformation were used for EEG analysis. Wavelet analysis was performed in non
      segmented full-length EEG. A specific wavelet-based algorithm was developed for
      the automatic identification of sleep spindles and SWD. None of standard wavelet
      templates provided precise identification of all sleep spindles and SWD in the
      EEG and different wavelet templates were imperative in order to accomplish this
      task. SWD were identified with high probability using standard Morlet wavelet,
      but sleep spindles were identified using two types of customized adoptive
      'spindle wavelets'. It was found that (1) almost 100% of SWD (but only 50-60% of
      spindles) were identified using the Morlet-based wavelet transform. (2) 82-91% of
      sleep spindles were selected using adoptive 'spindle wavelet 1' (template's peak
      frequency approximately 12.2 Hz), the remaining sleep spindles with 'spindle
      wavelet 2' (peak frequency approximately 20-25 Hz). (3) Sleep spindles and SWD
      were detected by the elevation of wavelet energy in different frequencies: SWD,
      in 30-50 Hz band, sleep spindles, in 7-14 Hz. It is concluded that the EEG
      patterns of sleep spindles and SWD belong to different families of phasic EEG
      events with different time frequency characteristics.

PMID- 19383512
TI  - Sensorimotor behavioral effects of endothelin-1 induced small cortical infarcts
      in C57BL/6 mice.
AB  - Mouse models have not paralleled rat models of stroke in advances in sensitive,
      species appropriate measures of neurological and behavioral recovery. Most
      available tests of mouse sensorimotor function are adaptations of those
      originally developed in rats and may not be as sensitive in detecting behavioral
      deficits after small cortical lesions in mice. Our purpose was to test the use of
      a vasoconstricting peptide, endothelin-1 (ET-1), to produce focal infarcts of the
      mouse sensorimotor cortex and to establish a behavioral test battery sensitive to
      resulting sensorimotor deficits. Young adult (3-5-month-old) male C57BL/6 mice
      received intracortical infusions of ET-1 that produced unilateral lesions of the
      forelimb region of the sensorimotor cortex, intracortical infusions of sterile
      saline, or sham surgeries. Pre-operatively and at various time points over 3
      weeks post-surgery, they were administered a test battery that included measures
      of sensorimotor asymmetry (Corner and Bilateral Tactile Stimulation Tests),
      coordinated forepaw use (Cylinder and Ladder Rung Tests), and dexterous forepaw
      function (Pasta Matrix Reaching Test). ET-1 infusions resulted in consistently
      placed, focal cortical infarcts and forelimb impairments as measured with the
      Ladder Rung, Bilateral Tactile Stimulation, and Pasta Matrix Reaching Tests. On
      the Bilateral Tactile Stimulation and Pasta Matrix Reaching Tests, impairments
      persisted throughout the time span of observation (26 days). These results
      support ET-1 as a viable option for creating small, reproducible lesions of
      anatomical subregions in the mouse neocortex that result in lasting functional
      impairments in the forelimb, as observed with sufficiently sensitive measures.

PMID- 19383513
TI  - A computer-assisted odorized hole-board for testing olfactory perception in mice.
AB  - The present paper describes a behavioral setup, designed and built in our
      laboratory, allowing the systematic and automatic recording of performances in a
      large number of olfactory behavioral tests. This computerized monitoring system
      has the capability of measuring different aspects of olfactory function in mice
      using different paradigms including threshold evaluation, generalization tasks,
      habituation/dishabituation, olfactory associative learning, short-term olfactory
      memory with or without a spatial component, and olfactory preferences. In this
      paper, we first describe the hole-board apparatus and its software and then give
      the experimental results obtained using this system. We demonstrate that one
      single, easy-to-run experimental setup is a powerful tool for the study of
      olfactory behavior in mice that has many advantages and broad applications.

PMID- 19383514
TI  - Modeling spinal cord contusion, dislocation, and distraction: characterization of
      vertebral clamps, injury severities, and node of Ranvier deformations.
AB  - Spinal cord contusion and transection models are widely used for studying spinal
      cord injury (SCI). Clinically, however, other biomechanical injury mechanisms
      such as vertebral dislocation and distraction frequently occur, but these
      injuries are difficult to produce in animals. We mechanically characterize a
      vertebral clamping strategy that enables the modeling of vertebral dislocation
      and distraction injuries--in addition to the standard contusion paradigm--in the
      rat cervical spine. These vertebral clamps have a stiffness of 83.6+/-18.9 N/mm
      and clamping strength 64.7+/-10.2N which allows injuries to be modeled at high
      speed (approximately 100 cm/s). Logistic regression indicated that a moderate-to
      severe injury, with an acute mortality rate of 10%, occurs at 2.6 mm of C4/5
      dorso-ventral dislocation and 4.1 mm of rostro-caudal distraction between C4 and
      C5. Injuries produced by dislocation and distraction exhibited features of axonal
      damage that were absent in contusion injuries. We conducted morphometric analysis
      at the nodes of Ranvier using immunohistochemistry for potassium channels (Kv1.2)
      in the juxtaparanodal region. Following distraction injuries, elongated nodes of
      Ranvier were observed up to 4mm rostral to the lesion. In contrast, contusion
      injuries produced distortions in nodal geometry which were restricted to the
      vicinity of the lesion. The greatest deformations in node of Ranvier geometry
      occurred at the dislocation epicenter. Given the importance of white matter
      damage in SCI pathology, the distinctiveness of these injury patterns demonstrate
      that the dislocation and distraction injury models complement existing contusion
      models. Together, these three animal models span a broader clinical spectrum for
      more reliably gauging the potential human efficacy of therapeutic strategies.

PMID- 19383515
TI  - Sensor-driven four-channel stimulation of paretic leg: functional electrical
      walking therapy.
AB  - This study introduces a Functional Electrical Therapy (FET) system based on
      sensor-driven electrical stimulation for the augmentation of walking. The
      automatic control relates to the timing of stimulation of four muscles. The
      sensor system comprises accelerometers and force-sensing resistors. The automatic
      control implements IF-THEN rules designed by mapping of sensors and muscle
      activation patterns. The new system was tested in 13 acute stroke patients
      assigned to a FET group or a control (CON) group. Both groups were treated with a
      standard rehabilitation program and 45min of walking daily for 5 days over the
      course of 4 weeks. The FET group received electrical stimulation during walking.
      The Fugl-Meyer (FM) test for the lower extremities, Barthel Index (BI), mean
      walking velocity (v(mean)) over a 6-m distance, and Physiological Cost Index
      (PCI) were assessed at the entry point and at the end of the treatment. Subjects
      within the FET and CON groups had comparable baseline outcome measures. In the
      FET group, we determined significant differences in the mean values of all
      outcomes between the entry and end points of treatment (p<0.05), contrary to the
      CON group where we found no significant differences (p>0.05). We also found
      significant differences in the changes of FM, BI, v(mean) and PCI which occurred
      during the 4 weeks of treatment between the FET and CON groups (p<0.05). The
      statistical strength of the clinical study was low (<70%), suggesting the need
      for a larger, randomized clinical trial.

PMID- 19383516
TI  - The major cathepsin L secreted by the invasive juvenile Fasciola hepatica prefers
      proline in the S2 subsite and can cleave collagen.
AB  - Secreted cysteine proteases are major players in host-parasite interactions; in
      Fasciola hepatica, a distinct group of cathepsins L was found to be predominantly
      expressed in the juvenile stages, but their enzymatic properties were unknown.
      Cathepsin L3 (FhCL3) is a main component of the juvenile secretory products and
      may participate in invasion. To characterize the biochemical properties, the
      proenzyme was expressed in the methylotrophic yeast Hansenula polymorpha and the
      mature enzyme was obtained from the culture medium. FhCL3 exhibited optimal
      activity and stability at neutral pH and a noticeable restricted substrate
      specificity with 70-fold preference for Tos-Gly-Pro-Arg-AMC over typical
      cathepsin substrates with hydrophobic or aliphatic residues in the S2 position.
      Accordingly, FhCL3 efficiently cleaved type I collagen over different pH and
      temperature conditions, but it did not cleave immunoglobulin. While most
      cathepsin cysteine proteinases are unable to digest collagen, mammalian cathepsin
      K, adult F. hepatica FhCL2 and the plant zingipain can also cleave collagen and
      substrates with Pro in P2 position, but only FhCL3 and zingipain hydrolyze these
      substrates with the highest efficiency. Molecular modeling and structural
      comparisons of the collagen cleaving cathepsins indicated that the strong
      substrate selectivity observed might be due to steric restrictions imposed by
      bulky aromatic residues at the S2-S3 subsites. The remarkable similarities of the
      active site clefts highlight the evolutive constrains acting on enzyme function.
      The presence of a collagen cleaving enzyme in F. hepatica juvenile stages is
      suggestive of a role in tissue invasion, an essential feature for the
      establishment of the parasites in their host.

PMID- 19383517
TI  - Expressed sequence tags of the peanut pod nematode Ditylenchus africanus: the
      first transcriptome analysis of an Anguinid nematode.
AB  - In this study, 4847 expressed sequenced tags (ESTs) from mixed stages of the
      migratory plant-parasitic nematode Ditylenchus africanus (peanut pod nematode)
      were investigated. It is the first molecular survey of a nematode which belongs
      to the family of the Anguinidae (order Rhabditida, superfamily Sphaerularioidea).
      The sequences were clustered into 2596 unigenes, of which 43% did not show any
      homology to known protein, nucleotide, nematode EST or plant-parasitic nematode
      genome sequences. Gene ontology mapping revealed that most putative proteins are
      involved in developmental and reproductive processes. In addition unigenes
      involved in oxidative stress as well as in anhydrobiosis, such as LEA (late
      embryogenesis abundant protein) and trehalose-6-phosphate synthase were
      identified. Other tags showed homology to genes previously described as being
      involved in parasitism (expansin, SEC-2, calreticulin, 14-3-3b and various
      allergen proteins). In situ hybridization revealed that the expression of a
      putative expansin and a venom allergen protein was restricted to the gland cell
      area of the nematode, being in agreement with their presumed role in parasitism.
      Furthermore, seven putative novel candidate parasitism genes were identified
      based on the prediction of a signal peptide in the corresponding protein sequence
      and homologous ESTs exclusively in parasitic nematodes. These genes are
      interesting for further research and functional characterization. Finally, 34
      unigenes were retained as good target candidates for future RNAi experiments,
      because of their nematode specific nature and observed lethal phenotypes of
      Caenorhabditis elegans homologs.

PMID- 19383518
TI  - Analgesic effect of milnacipran is associated with c-Fos expression in the
      anterior cingulate cortex in the rat neuropathic pain model.
AB  - The objective of the present study was to examine whether milnacipran, a
      serotonin-noradrenaline reuptake inhibitor, has an analgesic effect in rats with
      neuropathic pain. In addition, the c-Fos expression was investigated in the
      supraspinal sites of the brain and in the spinal dorsal horn in association with
      the nociceptive processing in rats with neuropathic pain produced by chronic
      constriction injury (CCI) in the sciatic nerve. In the CCI-induced neuropathic
      rats, behavioral testing for determining the change in the withdrawal threshold
      to mechanical stimulation and immunohistochemical detection of c-Fos were both
      performed. The anti-allodynic effect derived from milnacipran gradually increased
      over the observation period, indicating that the delayed-onset analgesia might be
      elicited by the continuous administration of milnacipran. The increased level of
      c-Fos expression in the anterior cingulate cortex (ACC) induced by noxious
      mechanical stimulation was significantly inhibited by the continuous
      administration of milnacipran, indicating that milnacipran might cause a
      functional modification in the nociceptive processing in the ACC.

PMID- 19383520
TI  - Non viral vector delivery in vitro using fibrin hydrogels.

PMID- 19383521
TI  - Cellular siRNA delivery using cell-penetrating peptides modified for endosomal
      escape.
AB  - RNAi-mediated silencing of specific genes is a promising strategy for gene
      therapy. To utilize RNAi for therapy, an efficient and safe method for delivery
      of RNA into the cell cytosol is necessary. The plasma membrane is the primary,
      and most difficult, barrier for RNA to cross, because negatively charged RNA is
      strongly repulsed by the negatively charged membrane. A variety of cationic
      polymers can be used as RNA carriers by interacting with RNA and covering its
      negative charges to form a cell-penetrating complex. Among the emerging
      candidates for RNA carriers are cationic cell-penetrating peptides (CPPs), which
      can cross the plasma membrane and internalize into cells together with RNA. This
      review focuses on CPP-based RNA delivery strategies. In using CPP-based RNA
      delivery, most of the RNA internalized by the cell is entrapped in endosomes.
      Strategies for endosomal escape of RNAs are also reviewed.

PMID- 19383519
TI  - Lipids and membrane microdomains in HIV-1 replication.
AB  - Several critical steps in the replication cycle of human immunodeficiency virus
      type 1 (HIV-1) - entry, assembly and budding - are complex processes that take
      place at the plasma membrane of the host cell. A growing body of data indicates
      that these early and late steps in HIV-1 replication take place in specialized
      plasma membrane microdomains, and that many of the viral and cellular components
      required for entry, assembly, and budding are concentrated in these microdomains.
      In particular, a number of studies have shown that cholesterol- and sphingolipid
      enriched microdomains known as lipid rafts play important roles in multiple steps
      in the virus replication cycle. In this review, we provide an overview of what is
      currently known about the involvement of lipids and membrane microdomains in HIV
      1 replication.

PMID- 19383523
TI  - MCH: From melanin-concentration to mega-consumption.

PMID- 19383522
TI  - In vitro assessments of nanomaterial toxicity.
AB  - Nanotechnology has grown from a scientific interest to a major industry with both
      commodity and specialty nanomaterial exposure to global populations and
      ecosystems. Sub-micron materials are currently used in a wide variety of consumer
      products and in clinical trials as drug delivery carriers and imaging agents. Due
      to the expected growth in this field and the increasing public exposure to
      nanomaterials, both from intentional administration and inadvertent contact,
      improved characterization and reliable toxicity screening tools are required for
      new and existing nanomaterials. This review discusses current methodologies used
      to assess nanomaterial physicochemical properties and their in vitro effects.
      Current methods lack the desired sensitivity, reliability, correlation and
      sophistication to provide more than limited, often equivocal, pieces of the
      overall nanomaterial performance parameter space, particularly in realistic
      physiological or environmental models containing cells, proteins and solutes.
      Therefore, improved physicochemical nanomaterial assays are needed to provide
      accurate exposure risk assessments and genuine predictions of in vivo behavior
      and therapeutic value. Simpler model nanomaterial systems in buffer do not
      accurately duplicate this complexity or predict in vivo behavior. A diverse
      portfolio of complementary material characterization tools and bioassays are
      required to validate nanomaterial properties in physiology.

PMID- 19383524
TI  - Acceptable risk of contact allergy in the general population assessed by CE-DUR-
      a method to detect and categorize contact allergy epidemics based on patient
      data.
AB  - Over the 20th century, several contact allergy epidemics arose in Western Europe.
      Today, industries use various assays to determine the sensitization potential of
      new ingredients and thereby prevent new contact allergy outbreaks. This study
      debates acceptable risk of sensitization in the general population by using a new
      epidemiological tool. The clinical epidemiology (CE) and drug utilization
      research (DUR) method recently estimated the 10-year contact allergy prevalence
      in the general population in Germany and Denmark based on patch test reading data
      in combination with an estimate of the number of persons eligible for patch
      testing each year based on patch test sales data. A reverse CE-DUR was performed
      to make delineations between the 10-year prevalence of contact allergy in the
      general population and the corresponding theoretical prevalences of contact
      allergy observed among patients with dermatitis in Denmark and Germany. Results
      indicated that if 1/100 subjects in the general population in Denmark and Germany
      had contact allergy; dermatologists would observe a prevalence of contact allergy
      among dermatitis patients was between 4.5-8.0% and 2.5-10.4%, respectively. The
      reverse CE-DUR approach can be used to alert public health authorities if the
      estimated number of sensitized persons in the general population is above a
      certain threshold.

PMID- 19383525
TI  - Organization and dynamics of tryptophan residues in tetrameric and monomeric
      soybean agglutinin: studies by steady-state and time-resolved fluorescence,
      phosphorescence and chemical modification.
AB  - We have investigated the organization and dynamics of tryptophan residues in
      tetrameric, monomeric and unfolded states of soybean agglutinin (SBA) by
      selective chemical modification, steady-state and time-resolved fluorescence, and
      phosphorescence. Oxidation with N-bromosuccinimide (NBS) modifies two tryptophans
      (Trp 60 and Trp 132) in tetramer, four (Trp 8, Trp 203 and previous two) in
      monomer, and all six (Trp 8, Trp 60, Trp 132, Trp 154, Trp 203 and Trp 226) in
      unfolded state. Utilizing wavelength-selective fluorescence approach, we have
      observed a red-edge excitation shift (REES) of 10 and 5 nm for tetramer and
      monomer, respectively. A more pronounced REES (21 nm) is observed after NBS
      oxidation. These results are supported by fluorescence anisotropy experiments.
      Acrylamide quenching shows the Stern-Volmer constant (K(SV)) for tetramer,
      monomer and unfolded SBA being 2.2, 5.0 and 14.6 M(-1), respectively. Time
      resolved fluorescence studies exhibit biexponential decay with the mean lifetime
      increasing along tetramer (1.0 ns) to monomer (1.9 ns) to unfolded (3.6 ns).
      Phosphorescence studies at 77 K give more structured spectra, with two (0,0)
      bands at 408.6 (weak) and 413.2 nm for tetramer. However, a single (0,0) band
      appears at 411.8 and 407.2 nm for monomer and unfolded SBA, respectively. The
      exposure of hydrophobic surface in SBA monomer has been examined by 8-anilino-1
      naphthalenesulfonate (ANS) binding, which shows approximately 20-fold increase in
      ANS fluorescence compared to that for tetramer. The mean lifetime of ANS also
      shows a large increase (12.0 ns) upon binding to monomer. These results may
      provide important insight into the role of tryptophans in the folding and
      association of SBA, and oligomeric proteins in general.

PMID- 19383526
TI  - Analysis of protein contacts into Protein Units.
AB  - Three-dimensional structures of proteins are the support of their biological
      functions. Their folds are maintained by inter-residue interactions which are one
      of the main focuses to understand the mechanisms of protein folding and
      stability. Furthermore, protein structures can be composed of single or multiple
      functional domains that can fold and function independently. Hence, dividing a
      protein into domains is useful for obtaining an accurate structure and function
      determination. In previous studies, we enlightened protein contact properties
      according to different definitions and developed a novel methodology named
      Protein Peeling. Within protein structures, Protein Peeling characterizes small
      successive compact units along the sequence called protein units (PUs). The
      cutting done by Protein Peeling maximizes the number of contacts within the PUs
      and minimizes the number of contacts between them. This method is so a relevant
      tool in the context of the protein folding research and particularly regarding
      the hierarchical model proposed by George Rose. Here, we accurately analyze the
      PUs at different levels of cutting, using a non-redundant protein databank.
      Distribution of PU sizes, number of PUs or their accessibility are screened to
      determine their common and different features. Moreover, we highlight the
      preferential amino acid interactions inside and between PUs. Our results show
      that PUs are clearly an intermediate level between secondary structures and
      protein structural domains.

PMID- 19383527
TI  - Moonlighting protein in Starkeyomyces koorchalomoides: characterization of
      dihydrolipoamide dehydrogenase as a protein acetyltransferase utilizing
      acetoxycoumarin as the acetyl group donor.
AB  - In this report we have identified for the first time a transacetylase (TAase) in
      a mesophilic fungi Starkeyomyces koorchalomoides catalyzing the transfer of
      acetyl group from polyphenolic acetate (PA) to a receptor protein glutathione S
      transferase (GST). An elegant assay procedure was established for TAase based on
      its ability to mediate inhibition of GST by 7,8-diacetoxy-4-methylcoumarin
      (DAMC), a model PA. Utilizing this assay procedure, S. koorchalomoides TAase was
      purified to homogeneity. TAase was found to have MW of 50 kDa. The purified
      enzyme exhibited maximum activity at 45 degrees C at pH 6.8. The N-terminal
      sequence of purified fungal TAase (ANDASTVED) showed identity with corresponding
      N-terminal sequence of dihydrolipoamide dehydrogenase (LADH), a mitochondrial
      matrix enzyme and an E3 component of pyruvate dehydrogenase complex (PDHC). TAase
      was found to have all the properties of LADH and avidly interacted with the anti
      LADH antibody. TAase catalyzed acetylation of GST by DAMC was identified by LC
      MS/MS and a single lysine residue (Lys-113) was found to be acetylated. Further,
      recombinant LADH from Streptococcus pneumoniae lacking lipoyl domain was found to
      exhibit little TAase activity, suggesting the role of lipoyl domain in the TAase
      activity of LADH. These observations bear evidence for the protein
      acetyltransferase activity of LADH. Such an activity of LADH can be attributed as
      a moonlighting function of the enzyme.

PMID- 19383528
TI  - Inhibitory postsynaptic membrane specializations are formed in gephyrin-deficient
      mice.
AB  - Gephyrin is a major postsynaptic scaffolding protein at GABAergic and glycinergic
      inhibitory synapses. Gephyrin-deficient (geph(-/-)) mice die after birth due to
      disinhibition of motor and sensory pathways resulting from a lack of postsynaptic
      glycine receptor and GABA(A) receptor clusters. Here, immunoelectron and confocal
      microscopy revealed that postsynaptic membrane specializations are formed in the
      absence of gephyrin. First, in brainstem sections obtained from newborn geph(-/-)
      mice inhibitory nerve terminals identified by immunogold labeling of either the
      vesicular inhibitory amino acid transporter (VIAAT) or GABA were found to be
      apposed to postsynaptic membrane areas decorated by electron-dense material.
      Second, neuroligin-2, a membrane protein of inhibitory postsynapses, was
      clustered beneath glutamate decarboxylase 65 (GAD-65) positive nerve terminals in
      geph(-/-) hippocampal cultures. These results indicate that proteins other than
      gephyrin define the ultrastructure of inhibitory postsynaptic membrane
      specializations.

PMID- 19383529
TI  - Impaired fear response in mice lacking GIT1.
AB  - G protein-coupled receptor kinase interacting protein 1 (GIT1) belongs to the
      family of Arf GAP proteins and has been implicated in the regulation of G protein
      coupled receptor (GPCR) sequestration, cell migration, synapse formation and
      dendritic spine morphogenesis in neurons. To extend these cellular studies on
      GIT1 to an in vivo system, we generated mice with globally inactivated Git1 gene
      by breeding mice carrying a conditional Git1(flox) allele with mice expressing
      the CMV-Cre transgene. Although many GIT1 knockout (GIT1-KO) animals died shortly
      after birth, homozygous mutants that survived the early post-partum period
      developed normally into adulthood and were fertile. Behavioral analyses of adult
      GIT1-KO mice revealed normal exploratory, anxiety- and depressive-like behaviors.
      However, GIT1-KO mice show impaired responses to fear conditioning and fear
      potentiated startle. Overall, these findings suggest that GIT1 is involved in the
      regulation of amygdala-mediated experience-based emotional behaviors.

PMID- 19383530
TI  - Effect of nigrostriatal damage induced by 6-hydroxydopamine on the expression of
      glial cell line-derived neurotrophic factor in the striatum of the rat.
AB  - Several types of brain injuries have been associated with alterations in the
      striatal expression of neurotrophic factors, including glial cell line-derived
      neurotrophic factor (GDNF). However, contradictory results on the striatal
      expression of GDNF have been reported in different animal models of Parkinson's
      disease. For this reason, we examined the effect of nigrostriatal damage on the
      mRNA and protein expression levels of GDNF in the striatum as a function of time
      following a striatal or medial forebrain bundle 6-hydroxydopamine lesion. At
      different time points after the administration of 6-hydroxydopamine, striatal
      expression levels of GDNF were analyzed with semi-quantitative Western blotting.
      No significant changes in GDNF expression levels were observed within the 35-day
      observation period, either between the denervated and the intact striatum of
      medial forebrain bundle and striatally lesioned rats or between the striata of
      lesioned animals and those of control animals. In order to reinforce these
      results, striata of lesioned rats, sacrificed 18 days after lesioning, were
      analyzed with enzyme-linked immunosorbent assay and real-time polymerase chain
      reaction. At this time point, both techniques confirmed the results of the
      Western blot analysis, detecting no changes in striatal expression of GDNF,
      either at the protein level, or at the mRNA level. These data show that
      nigrostriatal damage induced by 6-hydroxydopamine has no effect on the striatal
      expression of GDNF.

PMID- 19383531
TI  - Improved properties of incorporated chitosan film with ethyl cellulose
      microspheres for controlled release.
AB  - In this article, to discover an innovative drug release system, ciprofloxacin
      hydrochloride-loaded blending films of chitosan (CS)/ethyl cellulose (EC)
      microspheres were prepared. Two steps were adopted in the film forming process.
      The first was formation of the drug-loaded EC microspheres in CS solution by
      solvent remove/solvent evaporation methods; then, the composite films were made
      by casting and solvent evaporation. The results were that the drug-loaded round
      EC microspheres dispersed asymmetrically in the CS films and largely improved the
      release time. Moreover, the drug-loaded blending film containing 0.5 g EC
      microspheres prepared at 90 degrees C showed highlighted extended release
      property. The drug was stable in the blending films, which expressed good
      cytocompatibility proved by MTT test. The film should be a promising carrier for
      controlled and extended drug release system in pharmaceutical applications.

PMID- 19383532
TI  - Approach to design push-pull osmotic pumps.
AB  - Despite more than 30 years of clinical use, only few studies have been published
      reporting on the release mechanism underlying the drug delivery from push-pull
      osmotic pumps (PPOP). The aim of this study is to understand which factors have
      an effect on the drug delivery for modelling the drug release and to develop a
      mathematical model predictive of the drug release kinetics. The influence of the
      drug property was tested on two model drugs, isradipine (ISR) and
      chlorpheniramine (CPA) which are respectively practically insoluble and freely
      soluble. Results show that, regardless of the drug properties which do not
      significantly affect the drug delivery, the release kinetics is mainly controlled
      by four factors, (i) the PEG proportion in the membrane, (ii) the tablet surface
      area, (iii) the osmotic agent proportion and (iv) the drug layer polymer grade.
      The influence of each key formulation factors on the release mechanism was
      investigated defining their applicability range. A mathematical approach was
      developed to predict the drug delivery kinetics varying the PPOP controlling
      factors and helps to more efficiently design PPOP.

PMID- 19383533
TI  - A novel ex vivo skin model for the assessment of the potential transcutaneous
      anti-inflammatory effect of topically applied Harpagophytum procumbens extract.
AB  - Using ex vivo skin as a model, this work tested the hypothesis that the major
      pharmacologically active components of topically applied Harpagophytum procumbens
      (H. procumbens) can elicit anti-inflammatory responses in deeper tissues post
      transcutaneous delivery. Using Franz-type diffusion cells, ethanol extract of
      powdered H. procumbens tuber was dosed onto freshly excised porcine skin. After
      24 h the receptor phase was recovered, analysed for the major glycosides of DC,
      then used directly to dose further freshly excised skin membranes. After 6h the
      skin was recovered and probed for the expression of the three major enzymes
      involved in the inflammatory factors: cyclooxygenase (COX-2) and its product
      prostaglandin E2 (PGE-2), lipoxygenase (5-LOX), and inducible nitric oxide
      (iNOS), using immunocytochemistry and Western blotting analyses. It was found
      that the receptor phase at 24 h contained (0.8, 25, 1.8, 3 x 10(-3)) micromol mL(
      1) of harpagoside, harpagide, verbascoside, 8-O-p-coumaroyl-harpagide,
      respectively. When applied to skin, this solution effectively inhibited the
      expression of COX-2 and its product PGE-2. However, it did not have a significant
      effect on either 5-LOX or iNOS compared to control samples (PBS only). These data
      support the hypothesis that the transcutaneous delivery of H. procumbens can
      treat inflammation in deeper tissues such as in arthritis. Moreover, a novel ex
      vivo model has been described for assessing the potential anti-inflammatory
      activity of permeants delivered to deeper subcutaneous regions.

PMID- 19383534
TI  - Virtual channel discrimination is improved by current focusing in cochlear
      implant recipients.
AB  - Cochlear implant users' spectral resolution is limited by both the number of
      implanted electrodes and channel interactions between electrodes. Current
      steering (virtual channels) between two adjacent monopolar electrodes has been
      used to increase the number of spectral channels across the electrode array.
      However, monopolar stimulation is associated with large current spread and
      increased channel interaction. Current focusing across three adjacent electrodes
      (tripolar stimulation) has been used to reduce electrode current spread and
      improve channel selectivity. In the present study, current steering and current
      focusing were combined within a four-electrode stimulation pattern (quadrupolar
      virtual channels), thereby addressing the need for both increased channels and
      reduced current spread. Virtual channel discrimination was measured in 7 users of
      the Advanced Bionics Clarion II or HiRes 90K implants; virtual channel
      discrimination was compared between monopolar and quadrupolar virtual channels at
      three stimulation sites. The results showed that quadrupolar virtual channels
      provided better spectral resolution than monopolar virtual channels. The results
      suggested that quadrupolar virtual channels might provide the "best of both
      worlds" improving the number of spectral channels while reducing channel
      interactions.

PMID- 19383535
TI  - Topographical and cellular distribution of perineuronal nets in the human
      cochlear nucleus.
AB  - Specialized constructs of the extracellular matrix termed perineuronal nets
      surround the soma, primary dendrites and initial axon segment of some but not all
      neuronal populations in the central nervous system. In an effort to determine the
      cellular localization of perineuronal nets in the human cochlear nucleus (CN), we
      first performed a quantitative morphometric study of the human CN. We provide
      evidence for a laminar organization in the human dorsal cochlear nucleus (DCN;
      including molecular, granular and deep layers) as in other laboratory animals.
      Additionally, we find that the human ventral cochlear nucleus (VCN) contains
      distinct octopus, stellate, globular and spherical bushy cell populations, as
      described in other species. Using Wisteria floribunda histochemistry in five
      human brainstems, we identified perineuronal nets in the human cochlear nucleus.
      Perineuronal nets are associated with the vast majority of octopus and stellate
      cells in the caudal VCN. In the rostral VCN, dense perineuronal nets are
      associated with globular bushy cells and faint nets are associated with some
      spherical bushy cells and stellate cells. Few perineuronal nets are found in the
      DCN.

PMID- 19383536
TI  - B cell precursors are targets for Salmonella infection.
AB  - We previously reported that, in mice, B cells are a reservoir for bacteria during
      Salmonella infection. Here, we show that, within the bone marrow, B cells and
      their precursors are targeted for infection by Salmonella enterica serovar
      typhimurium. Our data suggest that B cells within the bone marrow may be a
      bacterial niche during chronic Salmonella infection.

PMID- 19383537
TI  - The immediate early genes, c-fos, c-jun and AP-1, are early markers of platinum
      analogue toxicity in human proximal tubular cell primary cultures.
AB  - These studies tested the hypothesis that c-fos, c-jun and AP-1 are early markers
      of platinum analogue-induced proximal tubule nephrotoxicity in primary rat
      proximal tubule (RPT) and human proximal tubule (HPT) cell cultures. The order of
      platinum analogue toxicity was cisplatin>transplatin>carboplatin in RPT and HPT
      cultures. Following a 2-h platinum analogue treatment, c-fos protein expression
      correlated with toxicity. Maximal c-fos protein levels were observed at 8-h (RPT)
      and 4-h (HPT) post-platinum analogue treatment. c-jun and AP-1 protein levels
      were maximal 4-h and 8-h, respectively, post cisplatin treatment in HPT cultures.
      In contrast, c-jun and AP-1 protein were not detected in RPT cultures. c-fos and
      c-jun mRNA levels were maximal at 60 and 120-min in RPT cell cultures,
      respectively, whilst c-fos and c-jun mRNA levels were maximal at 120-min in HPT
      cultures. Differences between HPT and RPT responses to cisplatin reveal inter
      species differences associated with induction of c-fos and c-jun mRNA and
      protein, which in turn form the functional AP-1 complex prior to the onset of
      cellular toxicity. These studies highlight the utility of HPT cultures as an
      invitro model system, and the potential of c-fos and c-jun as early markers of
      nephrotoxicity to screen therapeutic lead compounds.

PMID- 19383538
TI  - The influence of polychlorinated biphenyls (PCBs),
      dichlorodiphenyltrichloroethane (DDT) and its metabolite
      dichlorodiphenyldichloroethylene (DDE) on mRNA expression for NP-I/OT and PGA,
      involved in oxytocin synthesis in bovine granulosa and luteal cells.
AB  - The effect of polychlorinated biphenyls (PCBs) congeners (PCB 77, PCB 126, PCB
      153) and their technical mixture-Aroclor (Ar) 1248, as well as
      dichlorodiphenyltrichloroethane (DDT) and its metabolite
      dichlorodiphenyldichloroethylene (DDE; two individual isomers p,p'- and o,p'- or
      their mixture, 95% and 5%, respectively) at the dose of 10 ng/ml each, on the
      gene expression of (a) oxytocin (OT) precursor-neurophysin-oxytocin (NP-I/OT) and
      (b) peptidyl glycine-alpha-amidating mono-oxygenase (PGA), the terminal enzyme in
      the pathway of OT synthesis, was studied. Granulosa cells from follicles >1cm in
      diameter, collected on days 19-21 of estrous cycle, and luteal cells from corpora
      lutea (CL) collected on days 8-12 of the estrous cycle were used. The cells were
      incubated (6h) with these xenobiotics and the expression of NP-I/OT and PGA genes
      was determined. All PCBs increased (P<0.05) NP-I/OT gene expression in granulosa
      cells. Similarly, all PCBs but PCB 126 increased (P<0.05) PGA gene expression in
      these cells. DDT and DDE increased (P<0.05) gene expression of NP-I/OT in
      granulosa cells, while gene expression of PGA in these cells was stimulated
      (P<0.05) by DDE only. The mRNA expression for NP-I/OT and PGA in luteal cells was
      increased (P<0.05) by PCB 77 and PCB 153. Both DDE isomers and mixture also
      stimulated (P<0.05) of NP-I/OT mRNA expression, while increase (P<0.05) of PGA
      mRNA expression was elicited by incubation of these cells with DDE mixture and Ar
      1248. Obtained data suggest that PCBs, DDT and DDE can affect the mRNA expression
      for NP-I/OT and PGA in bovine granulosa and luteal cells.

PMID- 19383539
TI  - Effects of prenatal exposure to Tityus bahiensis scorpion venom on rat offspring
      development.
AB  - Scorpion envenoming is a public health problem. In Brazil, the scorpion Tityus
      serrulatus is considered the most dangerous, but a large number of exposures also
      occur with Tityus bahiensis. There are quite a few studies in literature about
      the toxic effects of this venom but it is not known if the venom causes
      malformations or behavioral defects to the offspring of mothers exposed to the
      venom during pregnancy. The objective of this work was to determine, in rats, the
      possible toxic effects of T. bahiensis venom on offspring when injected into rats
      during different periods of fetal development. Rats were assigned to one of three
      groups: one control group and two experimental groups that were subcutaneously
      injected with venom (2.5mg/kg) on the 10th (GD10) or on 16th day (GD16) of
      gestation. Pups were evaluated for changes in physical and behavioral
      development. GD10 treatment group offspring showed an increase in body weight
      gain, earlier ear unfolding, incisor tooth eruption and vaginal opening. A
      decrease in the time of palmar grasp and surface-righting reflexes was observed
      only for males. In GD16 treatment group, earlier ear unfolding, incisor tooth
      eruption, and delay in eye opening were observed in the offspring. In female pups
      a decrease in weight gain and in time for palmar grasp reflex, and an increase in
      time for negative geotaxis were observed. In male pups a delay in the testis
      descent, decrease in the time of palmar grasp, increase in the time of negative
      geotaxis reflex and in the general and locomotor activities could be noticed.
      Therefore, we concluded that a moderate dose of scorpion venom administered to
      pregnant rats was able to elicit alterations in physical and behavioral
      development in the offspring during the postnatal period.

PMID- 19383540
TI  - Genistein and ethinyl estradiol dietary exposure in multigenerational and chronic
      studies induce similar proliferative lesions in mammary gland of male Sprague
      Dawley rats.
AB  - Genistein and ethinyl estradiol (EE(2)) were examined in multigenerational
      reproductive and 2-yr chronic toxicity studies with different exposure durations
      across generations F(0) through F(4). Sprague-Dawley rats were exposed to
      genistein (0, 5, 100, or 500 ppm) or EE(2) (0, 2, 10, or 50 ppb). Effects in the
      male mammary gland are described here. In the multigeneration studies, mammary
      hyperplasia was induced by both compounds; the chronic studies had a lower
      incidence, without proportionate neoplasia. Sexual dimorphism (predominant
      tubuloalveolar growth in females and lobuloalveolar in males) was retained
      without feminization in high dose genistein or EE(2). In the continuously exposed
      generations, mammary hyperplasia was sustained but not amplified, appeared
      morphologically similar across all generations, and was not carried over into
      unexposed offspring of previously exposed generations. The hyperplasia in male
      rats was similar whether induced by genistein or EE(2). Results substantiate and
      extend previous reports that mammary gland hyperplasia in the male rat is one of
      the most sensitive markers of estrogenic endocrine disruption.

PMID- 19383541
TI  - In vitro and in vivo reproduction toxicology of 12 monoaminergic reuptake
      inhibitors: possible mechanisms of infrequent cardiovascular anomalies.
AB  - The rat Whole Embryo Culture (WEC) has been used to predict the potential
      teratogenicity of 12 selective/mixed monoaminergic reuptake inhibitors (MRUI).
      WEC results were compared with in vivo animal and human epidemiological
      teratogenicity data. In vitro, paroxetine and the positive control retinol were
      the only compounds identified as a clear teratogen, but developmental
      morphological indicators suggestive of a teratogenic potential were observed for
      most other MRUIs, including fluoxetine, citalopram and venlafaxine. No clear
      evidence of teratogenic potential was observed for three compounds, however, all
      compounds assessed showed a dose-dependent general embryotoxicity. In vivo
      testing of nine MRUIs for teratogenicity was limited by maternal toxicity (e.g.
      anorexia) without showing overt embryotoxicity (e.g. implantation loss). Next to
      complete absence, the cardiovascular (CV) anomalies observed (mostly) in rabbits
      ranged from a low incidence (e.g. above historical background of 0.35%) to a
      clear incidence (mean 4.1%). It is suggested that observed specific malformations
      in vitro (e.g. branchial bars deformed, displaced or additional otic system), not
      noted in any (historical) controls, may be early ontogenetic indicators for
      infrequent CV-anomalies observed in vivo. Despite the low incidence of anomalies
      in vitro or in vivo, they may yet be clinically relevant as in the case of
      paroxetine. Possible mechanisms are discussed, e.g. perturbed neural crest cell
      migration.

PMID- 19383542
TI  - Transcriptional control of human organic anion transporting polypeptide 2B1 gene.
AB  - Organic anion transporting polypeptides (OATPs) are a group of transmembrane
      carriers with a wide spectrum of amphipathic substrates. In particular, OATP2B1
      (previously called OATP-B) can transport steroid hormone conjugates and is
      expressed in organs with steroidogenic activity, such as placenta, brain and
      skin. In this work, we have analyzed the transcription of the OATP2B1 gene
      (SLCO2B1) in 14 different human tissues by means of 5'-RACE analysis. Five
      promoters (only two of which were present in GenBank), associated with distinct
      first exons, were found to drive OATP2B1 expression, giving rise to transcripts
      with unique 5'-untranslated termini. Exon 1b is widely expressed and was found
      here in 10 tissues. It is partially coding, while the other four different first
      exons are untranslated. All exons are spliced to a common exon 2 that contains a
      putative ATG in frame with the following coding region. Sequence analysis of the
      5'-flanking region of each first exon revealed a lack of TATA box, thus
      accounting for the use of multiple transcriptional start sites in nearly all
      first exons.

PMID- 19383543
TI  - Progesterone receptor A-regulated gene expression in mammary organoid cultures.
AB  - Progesterone, through the progesterone receptor (PR), promotes development of the
      normal mammary gland and is implicated in the etiology of breast cancer. We
      identified PRA-regulated genes by microarray analysis of cultured epithelial
      organoids derived from pubertal and adult mouse mammary glands, developmental
      stages with differing progesterone responsiveness. Microarray analysis showed
      significant progestin (R5020)-regulation of 162 genes in pubertal organoids and
      104 genes in adult organoids, with 68 genes regulated at both developmental
      stages. Greater induction of receptor activator of NFkappaB ligand and calcitonin
      expression was observed in adult organoids, suggesting possible roles in the
      differential progesterone responsiveness of the adult and pubertal mammary
      glands. Analysis of the R5020-responsive transcriptome revealed several enriched
      biological processes including cell adhesion, immune response, and survival.
      R5020 both induced Agtr1 and potentiated angiotensin II-stimulated proliferation,
      highlighting the functional significance of the latter process. Striking up
      regulation of genes involved in innate immunity processes included the leukocyte
      chemoattractants serum amyloid A1, 2 and 3 (Saa1, 2, 3). In vivo analysis
      revealed that progesterone treatment increased SAA1 protein expression and
      leukocyte density in mammary gland regions undergoing epithelial expansion. These
      studies reveal novel targets of PRA in mammary epithelial cells and novel
      linkages of progesterone action during mammary gland development.

PMID- 19383544
TI  - Central modifications of allopregnanolone and beta-endorphin following
      subcutaneous administration of Nestorone.
AB  - The aim of the present study was to evaluate the potential action of Nestorone
      (alone or in combination with estradiol valerate) on the level of
      allopregnanolone and of the opioid beta-endorphin in selected brain areas. Wistar
      ovariectomized rats were given 0.05 mg/(kg day) of estradiol valerate (E2V) or
      subcutaneous Nestorone at three dose levels: low dose (10 microg/(kg day)),
      antiovulatory dose (50 micro/(kg day)) and high dose (250 microg/(kg day)) with
      and without E2V. E2V therapy reversed the reduction of allopregnanolone and beta
      endorphin induced by ovariectomy anywhere was analyzed except for the adrenal
      gland. Nestorone showed no effect on allopregnanolone concentration in serum or
      any part of the brain tissue when given alone while it had a synergistic
      increasing effect in allopregnanolone concentration in some parts of the brain
      (hippocampus, hypothalamus, anterior pituitary and serum) when given at high dose
      of 250 microg/(kg day) in combination with E2V. At lower doses it possesses a
      synergistic effect with E2V only in the hippocampus (at 50 microg/(kg day)) and
      in the anterior pituitary (at 10 and 50 microg/(kg day)). Nestorone administered
      alone at any dose led to significant increase in beta-endorphin levels in the
      hippocampus only while, in the high dose group, there was a significant increase
      in endorphin levels in anterior pituitary and hypothalamus in addition to
      hippocampus as compared to ovariectomized control rats. In addition, only the
      highest dose of Nestorone added to estrogen increased beta-endorphin levels of
      hippocampus and plasma. Thus the lower doses of Nestorone alone or in combination
      with estrogen do not seem to exert any great effect on both allopregnanolone and
      beta-endorphin. It is only the highest dose of Nestorone that increases
      allopregnanolone and beta-endorphin levels in selected brain areas, which are the
      hippocampus, the hypothalamus, the anterior pituitary and serum/plasma. This
      suggests that Nestorone at the antiovulatory dose levels may not alter the
      positive effects of estrogen treatment on mood and behaviour.

PMID- 19383545
TI  - Progestins induce catalase activities in breast cancer cells through PRB isoform:
      correlation with cell growth inhibition.
AB  - Reactive oxygen species (ROS) have been suggested to participate in tumor
      emergence due to their mitogenic and apoptotic signaling, and as contributors to
      DNA structural damage. Here we report that progesterone and various synthetic
      steroids with progestin potencies (norethisterone acetate, MPA, and Tibolone)
      counteract cell growth induced by hydrogen peroxide (H(2)O(2)), through a potent
      induction of catalase activities, in breast cancer cells and normal human
      epithelial breast cells. At physiological concentrations, progesterone and the
      pure progestin, Org2058, displayed the most potent H(2)O(2) detoxification
      ability suggesting its effect was characteristic of its progestin potency. We
      also report on the enhancement of catalase activities by progesterone receptor
      isoform B (PRB), as determined from experiments using antiprogestins and MDA-MB
      231, cells engineered for the selective expression of progesterone receptor
      isoform A or B. The potent action of progesterone on catalase activities
      indicates its contribution to a beneficial role in breast cell homeostasis.

PMID- 19383546
TI  - Bacterially expressed recombinant WD40 domain of human Apaf-1.
AB  - The apoptotic protease activating factor (Apaf-1) is a protein that binds to
      cytochrome c, and in the presence of dATP/ATP oligomerizes to assume the role of
      an adaptor platform for activating the caspase-9 zymogen. In order to study the
      biochemical and structural details of Apaf-1 function, we have generated an
      expression construct from pcDNA 3-Apaf-1XL for production of the WD40 domain
      ((WD40)Apaf-1) in Escherichia coli. The WD40 domain expressed contains 825 amino
      acids in addition to an N-terminal His(6) tag derived from the cloning vector.
      The expressed protein is invariably localized in the inclusion body fraction of
      E. coli. A simple protocol involving Sephadex G100 chromatography developed for
      purifying the protein starting from inclusion bodies has allowed protein recovery
      in highly pure form. Basic fluorescence and CD spectra indicate that the refolded
      protein has extensive secondary and tertiary structures. Immunoprecipitation
      studies have provided qualitative information about the binding interaction of
      (WD40)Apaf-1 and cytochrome c. The binding interaction has been quantified by
      spectrophotometric titration of cytochrome c with recombinant (WD40)Apaf-1. The
      results demonstrate a weak binding for cytochrome c and (WD40)Apaf-1 interaction,
      the binding affinity being 390 nM. The analysis indicates a 2:1 or possibly even
      3:1 stoichiometry for cytochrome c and (WD40)Apaf-1 binding interaction.

PMID- 19383547
TI  - Inhibition of spicule elongation in sea urchin embryos by the
      acetylcholinesterase inhibitor eserine.
AB  - The activity of acetylcholinesterase (AchE) increases rapidly after the gastrula
      stage of sea urchin development. In this report, changes in activity and in the
      molecular differentiation of AchE were investigated. AchE activity increased
      slightly during gastrulation and rose sharply thereafter, and was dependent on
      new RNA synthesis. No activity of butyrylcholinesterase was found. Morphogenesis
      in sea urchin embryos was inhibited by the AchE inhibitor eserine, which
      specifically inhibited arm rod formation but not body rod formation. Spicule
      formation and enzyme activity in cultured micromeres were inhibited by eserine in
      a dose-dependent manner. During gastrulation, two molecular forms of AchE were
      detected with polyacrylamide gel electrophoresis. The appearance of an additional
      band on the gel was consistent with the occurrence of a remarkable increase in
      the enzyme activity. This additional band appeared as a larger molecular form in
      Anthocidaris crassispina, Hemicentrotus pulcherrimus, Stomopneustes variolaris,
      and Strongylocentrotus nudus, and as a smaller form in Clypeaster japonicus and
      Temnopleurus hardwicki. These results suggest that the change in the molecular
      form of AchE induced a change in enzymatic activity that in turn may play a role
      in spicule elongation in sea urchin embryos.

PMID- 19383548
TI  - Two metallothionein genes from mud loach Misgurnus mizolepis (Teleostei;
      Cypriniformes): gene structure, genomic organization, and mRNA expression
      analysis.
AB  - Two metallothionein genes, MLMT-IA and MLMT-IB, were isolated and characterized
      from the mud loach Misgurnus mizolepis (Teleostei; Cypriniformes). For these MTs,
      we determined a tandem "tail-to-head" genomic organizational pattern, identified
      conserved genomic features, showed high sequence identities in the coding
      regions, and examined the closest phylogenetic affiliation, suggesting their
      divergence by a recent gene duplication event. However, the 5'-flanking upstream
      regions in MLMT-IA and MLMT-IB exposed large differences in the composition and
      distribution patterns of various transcription factor binding motifs, especially
      regarding the organization of the metal response element clusters. Real-time RT
      PCR assays showed that mRNA levels of both MLMT-IA and MLMT-IB isoforms were
      variable among tissues and the ratios between them were also variable across
      tissues, although the MLMT-IA was always predominant in every adult tissue
      tested. We also found that the MLMT-IA and MLMT-IB mRNA expression levels were
      regulated dynamically during embryonic and larval development stages, in which
      the basal expression level of MLMT-IA was also consistently higher than that of
      MLMT-IB. Upon acute in vivo metal exposure to cadmium, chromium, copper, iron,
      manganese, nickel, or zinc at 5 microM for 48 h, the transcriptional modulations
      of MLMT-IA and MLMT-IB were quite different from each other and the type of
      response was affected significantly by the kind of metals and tissues.

PMID- 19383549
TI  - The effect of feed restriction on expression of hepatic lipogenic genes in
      broiler chickens and the function of SREBP1.
AB  - To study the role of sterol regulatory element-binding proteins (SREBP) in
      lipogenesis and cholesterol synthesis in the chicken, two experiments were
      carried out. In the first study, seven-week-old broilers (n=16) were allocated
      into 2 groups, fasted for 24 h or refed for 5 h after a 24 h fasting. The mRNA
      concentrations for SREBPs and other lipogenic genes in the liver were determined
      by quantitative real time PCR. The hepatic mRNA relative abundance of lipogenic
      genes and genes involved in cholesterol synthesis were significantly greater
      (p<0.001) in the refed broilers. Similar results were demonstrated with Northern
      analysis. The data suggest that in the liver of fasted broilers, genes associated
      with lipogenesis and cholesterol biosynthesis were inhibited. Indeed, the mRNA
      concentrations for fatty acid synthase (FAS), malic enzyme, and stearoyl coenzyme
      A desaturase were almost undetectable after the 24 h fasting. The data also
      demonstrated that the expression of lipogenic genes coordinate well as a group
      during the refeeding period. Second, three small interfering RNA (siRNA)
      oligonucleotides against SREBP1 were designed to be used in transfecting a
      chicken hepatocarcinoma cell line LMH. One of the three siRNAs effectively
      reduced SREBP1 mRNA concentration (p<0.01). The acetyl coenzyme A
      carboxylase(alpha) (ACC(alpha)) mRNA was also significantly reduced by the SREBP1
      siRNA treatment, suggesting that SREBP1 can upregulate the expression of this
      lipogenic gene. This siRNA, however, did not affect the mRNA for FAS. Taken
      together, the RNA interference study showed that SREBP1 has the ability to
      regulate the expression of ACC(alpha). This study has helped us understand more
      about the function of SREBP1 and the physiology of the broiler chickens.

PMID- 19383551
TI  - Mechanisms of primary cancer prevention by butyrate and other products formed
      during gut flora-mediated fermentation of dietary fibre.
AB  - Dietary fibres are indigestible food ingredients that reach the colon and are
      then fermented by colonic bacteria, resulting mainly in the formation of short
      chain fatty acids (SCFA) such as acetate, propionate, and butyrate. Those SCFA,
      especially butyrate, are recognised for their potential to act on secondary
      chemoprevention by slowing growth and activating apoptosis in colon cancer cells.
      Additionally, SCFA can also act on primary prevention by activation of different
      drug metabolising enzymes. This can reduce the burden of carcinogens and,
      therefore, decrease the number of mutations, reducing cancer risk. Activation of
      GSTs by butyrate has been studied on mRNA, protein, and enzyme activity level by
      real-time RT-PCR, cDNA microarrays, Western blotting, or photometrical
      approaches, respectively. Butyrate had differential effects in colon cells of
      different stages of cancer development. In HT29 tumour cells, e.g., mRNA GSTA4,
      GSTP1, GSTM2, and GSTT2 were induced. In LT97 adenoma cells, GSTM3, GSTT2, and
      MGST3 were induced, whereas GSTA2, GSTT2, and catalase (CAT) were elevated in
      primary colon cells. Colon cells of different stages of carcinogenesis differed
      in post-transcriptional regulatory mechanisms because butyrate increased protein
      levels of different GST isoforms and total GST enzyme activity in HT29 cells,
      whereas in LT97 cells, GST protein levels and activity were slightly reduced.
      Because butyrate increased histone acetylation and phosphorylation of ERK in HT29
      cells, inhibition of histone deacetylases and the influence on MAPK signalling
      are possible mechanisms of GST activation by butyrate. Functional consequences of
      this activation include a reduction of DNA damage caused by carcinogens like
      hydrogen peroxide or 4-hydroxynonenal (HNE) in butyrate-treated colon cells.
      Treatment of colon cells with the supernatant from an in vitro fermentation of
      inulin increased GST activity and decreased HNE-induced DNA damage in HT29 cells.
      Additional animal and human studies are needed to define the exact role of
      dietary fibre and butyrate in inducing GST activity and reducing the risk of
      colon cancer.

PMID- 19383550
TI  - G2A and LPC: regulatory functions in immunity.
AB  - The G2A receptor was originally identified by virtue of its transcriptional
      induction in murine B lymphoid cells in response to oncogenic transformation and
      treatment with various DNA-damaging agents. While preliminary characterization of
      cellular responses to G2A overexpression in fibroblastic cell lines suggested
      that this receptor may negatively regulate cell growth under conditions of
      proliferative and genotoxic stress, subsequent studies driven by the discovery of
      lysophosphatidylcholine (LPC) as a regulator of G2A signaling in immunoregulatory
      cells point to an important role for this receptor in innate and adaptive
      immunity.

PMID- 19383552
TI  - Serum creatine phosphokinase is helpful in distinguishing generalized tonic
      clonic seizures from psychogenic nonepileptic seizures and vasovagal syncope.
AB  - OBJECTIVE: Distinguishing epileptic generalized tonic-clonic seizures (GTCS) from
      either psychogenic nonepileptic seizures (PNES) or vasovagal syncope (VVS) is
      important. In this study, we investigated the use of postictal serum creatine
      phosphokinase (CPK) concentrations in distinguishing between these events.
      METHODS: Patients admitted to the Neurology Ward at Namazi Hospital in Shiraz,
      Iran, with an attack of transient loss of consciousness and abnormal movements
      witnessed by a neurologist were studied. We categorized the patients into three
      groups: 20 patients with GTCS, 22 with VVS, and 20 with PNES. A group of 20
      normal healthy individuals were included in the study as the control group. Serum
      CPK concentration was measured 12-15 h after the attack in all patients and at
      one time in the control group. A P value less than 5% was considered significant.
      RESULTS: There were no significant differences between the four groups with
      respect to age and sex. Mean CPK concentrations statistically significantly
      differed between the four groups, with higher levels in patients with GTCS
      (P=0.0001). Serum CPK concentration had a sensitivity of 75% and specificity of
      86% for the diagnosis of GTCS. CPK concentration was above 160 mg/dl in 75% of
      patients with GTCS, 15% of patients with PNES, 13.6% of patients with VVS, and
      15% of the control group (P=0.0001). The PNES, VVS, and control groups did not
      statistically significantly differ with respect to CPK concentrations.
      CONCLUSION: In patients with a recent loss of consciousness and abnormal
      movements, serum CPK concentration is a useful, practical, and relatively
      accurate parameter to assist in the differentiation of epileptic seizures from
      either VVS or PNES.

PMID- 19383553
TI  - Report on autoscopic or mirror hallucinations and altruistic hallucinations.

PMID- 19383554
TI  - Immunosuppressive effects of demethylzeylasteral in a rat kidney transplantation
      model.
AB  - In this study, we examined the immunosuppressive activity of demethylzeylasteral
      (T-96), isolated from the traditional Chinese herbal medicine, Tripterygium
      wilfordii Hook f. Its immunosuppressive effect was investigated using mouse
      splenocytes in vitro, and in an in vivo rat kidney transplant model. T-96
      inhibited mouse splenocyte proliferation in a dose dependent manner. In the rat
      kidney transplant study, rats were randomly divided into eight groups following
      kidney transplantation, and different doses of T-96 or cyclosporin A (CsA) were
      administered to each group. T-96 alone at doses of 10 or 20 mg/kg/day
      significantly prolonged the survival of kidney-transplanted rats, compared with
      transplanted but untreated control rats. A combination of T-96 and prednisone
      also significantly prolonged survival: 10 mg/kg/day T-96 with 10 mg/kg/day
      prednisone increased the survival time to 31.8+/-6.5 days. Moreover, the
      combination of T-96 and prednisone was also effective in suppressing rejection of
      rat transplanted kidneys. These results demonstrate the strong immunosuppressive
      activity of T-96 and suggest a possible clinical use for T-96 as an
      immunosuppressive agent in the fields of organ transplantation and autoimmune
      disorders.

PMID- 19383555
TI  - Central command and metaboreflex cardiovascular responses to sustained handgrip
      during microgravity.
AB  - Four subjects were studied before and during a 16-day space flight. The test
      included 2min of rest, 2min of sustained handgrip (SHG), and 2min of post
      exercise circulatory occlusion (PECO). Heart rate (HR) and mean arterial pressure
      (MAP) responses to central command and mechanoreceptor stimulation were
      determined from the difference between SHG and PECO. Responses to metaboreceptor
      stimulation were determined from the difference between PECO and rest. Late in
      flight (days 12-14) the central command/mechanoreceptor component of the HR
      response was reduced by 5bpm (P=0.01) from its pre-flight value of 15 (+/-3)bpm
      (mean (+/-SEM)). At the same time the metaboreflex responses of HR and MAP were
      unchanged. The attenuated HR response to central command was likely of baroreflex
      origin. Together with a parallel study of PECO after dynamic leg exercise, our
      data indicate that central processing of metaboreflex inputs is unchanged in
      microgravity whereas metaboreflex inputs from weight-bearing muscles are
      enhanced.

PMID- 19383556
TI  - Status of cardiovascular issues related to space flight: Implications for future
      research directions.
AB  - Compromised cardiovascular performance, occurrence of serious cardiac
      dysrhythmias, cardiac atrophy, orthostatic intolerance, reduced aerobic capacity,
      operational impacts of regular physical exercise, and space radiation are risks
      of space flight to the cardiovascular system identified in the 2007 NASA Human
      Integrated Research Program. An evidence-based approach to identify the research
      priorities needed to resolve those cardiovascular risks that could most likely
      compromise the successful completion of extended-duration space missions is
      presented. Based on data obtained from astronauts who have flown in space, there
      is no compelling experimental evidence to support significant occurrence of
      autonomic or vascular dysfunction, cardiac dysrhythmias, or manifestation of
      asymptomatic cardiovascular disease. The operational impact of prolonged daily
      exercise and space radiation needs to be defined. In contrast, data from the
      literature support the notion that the highest probability of occurrence and
      operational impact with space flight involving cardiovascular risks to astronaut
      health, safety and operational performance are reduced orthostatic tolerance and
      aerobic capacity, the resource cost of effective countermeasures, and the
      potential effects of space radiation. Future research should focus on these
      challenges.

PMID- 19383557
TI  - A fluoroscopic and laryngoscopic study of glossopharyngeal insufflation and
      exsufflation.
AB  - Glossopharyngeal breathing, frequently performed by elite breath-hold divers,
      relies on muscles of the mouth and pharynx to move air into (glossopharyngeal
      insufflation, GI) and out of the lungs (glossopharyngeal exsufflation, GE). GI
      has also been used by patients with weak respiratory muscles. Fluoroscopic and
      endoscopic examinations were performed on four divers (three of whom were world
      record holders) during both GI and GE maneuvers. A detailed pictorial description
      of both GI and GE, with online video material that includes external, endoscopic
      and fluoroscopic examinations, is provided in this publication. Both GI and GE
      are accomplished with a coordinated series of contractions by glossopharyngeal
      muscles and they rely on a piston pump-like action of the larynx. In particular,
      the larynx moves extensively and repeatedly up and down, to either inject air
      into (GI) or extract it from the lungs (GE), with the vocal cords functioning as
      a valve. During both maneuvers, when the larynx is in its highest position, the
      epiglottis does not fold back, unlike what happens during swallowing.

PMID- 19383558
TI  - Oxidative stress and HIF-1 alpha modulate hypoxic ventilatory responses after
      hypoxic training on athletes.
AB  - We investigated the strength of the association between oxidative stress, hypoxia
      inducible factor 1 (HIF-1 alpha) and acute hypoxic ventilatory response (AHVR)
      after hypoxic training in elite runners. Six elite runners were submitted to 18
      day of "living high-training low" (LHTL) and six performed the same training in
      normoxia. AHVR was measured during an acute hypoxic test before and after
      training. Plasma levels of protein oxidation (AOPP), malondialdehydes and (HIF-1
      alpha) mRNA in the leukocytes were measured before and after the acute hypoxic
      test. LHTL increased AHVR and amplified the responses of HIF-1 alpha mRNA and
      AOPP (Delta(AOPP)) to the acute hypoxic test. Furthermore, between PRE and POST,
      the changes in Delta(AOPP) were correlated with the changes in AHVR (r=0.69,
      P=0.01). The ventilatory acclimatization to hypoxia occurring in athletes after
      LHTL seems to be modulated by oxidative stress. Furthermore, LHTL induced a
      higher sensitivity of HIF-1 alpha mRNA to acute hypoxia in elite athletes.

PMID- 19383559
TI  - Elastic layer-structured metal organic frameworks (ELMs).
AB  - Elastic layer-structured metal organic frameworks (ELMs) having flexible two
      dimensional structure show a gate phenomenon in sorption/desorption of simple gas
      molecules. The gate phenomenon is accompanied by expansion/shrinkage of the
      layers. The gas sorption/desorption is not based on a physical adsorption, but on
      a chemical reaction, which includes high cooperativity. The cooperative reaction
      could be analyzed thermodynamically. The gate phenomenon showed advantages in
      separation of CO2 from mixed gases and in storage of CH4 owing to easy release of
      absorbed molecules.

PMID- 19383560
TI  - Uniform discotic wax particles via electrospray emulsification.
AB  - We present a novel colloidal discotic system: the formation and self-assembling
      of wax microdisks with a narrow size distribution. Uniform wax emulsions are
      first fabricated by electrospraying of melt alpha-eicosene. The size of the
      emulsions can be flexibly tailored by varying the flow rate of the discontinuous
      phase, its electric conductivity, and the applied voltage. The process of
      entrainment of wax droplets, vital for obtaining uniform emulsions, is
      facilitated by the reduction of air-water surface tension and the density of the
      continuous phase. Then uniform wax discotic particles are produced via phase
      transition, during which the formation of a layered structure of the rotator
      phase of wax converts the droplets, one by one, into oblate particles. The time
      span for the conversion from spherical emulsions to disk particles is linearly
      dependent on the size of droplets in the emulsion, indicating the growth of a
      rotator phase from surface to the center is the limiting step in the shape
      transition. Using polarized light microscopy, the self-assembling of wax disks is
      observed by increasing disk concentration and inducing depletion attraction among
      disks, where several phases, such as isotropic, condensed, columnar stacking, and
      self-assembly of columnar rods are present sequentially during solvent
      evaporation of a suspension drop.

PMID- 19383561
TI  - Biocompatible microemulsions of dicephalic aldonamide-type surfactants:
      formulation, structure and temperature influence.
AB  - The temperature effects upon microemulsion systems composed of dicephalic N
      dodecyl-N,N-bis[(3-D-aldonylamido)propyl]amines C12-DX (gluconyl GA or
      lactobionyl LA)/iso-butanol/hydrophilic (diethylene glycol monoethyl ether) or
      hydrophobic (iso-octane) oils/water were investigated by evaluating isotropic
      area magnitudes in the pseudoternary phase diagrams, as well as droplet
      characteristics by electron paramagnetic resonance (EPR) and dynamic light
      scattering (DLS) spectroscopies at 25, 40 and 55 degrees C. We concluded that in
      the examined systems a cosurfactant, such as middle-chain alcohol, was needed to
      obtain large mesophase isotropic areas. The phase behavior and structure of the
      examined systems were temperature insensitive but they were intimately determined
      by the nature of the C12-DX and the polarity of the oil phase. By adjusting the
      nature of the oil, as well as the surfactant hydrophilicity, the performed
      isotropic systems containing low amounts of nonaggressive surfactant could be
      formulated successfully. Interfacial properties and the dynamic structure of the
      surfactant/cosurfactant monolayer were studied by the spin probe technique using
      the 16-doxylstearic acid methyl ester (16-DSE) as the appropriate probe. The
      polarity of the interface was not affected by temperature but the interface
      rigidity was dependent upon the nature of the surfactant and oil as well as on
      temperature. The size of the dispersed domains, evaluated by dynamic light
      scattering (DLS), was found to be a function of temperature, surfactant content
      and type of additives. The investigated o/w microemulsions (i.e., ranging from
      3.0 to 8.8 nm) constituted promising templates for a variety of syntheses of
      nanostructures with small size and high-capacity solubilizing media.

PMID- 19383562
TI  - Transport of carboxymethyl cellulose stabilized iron nanoparticles in porous
      media: column experiments and modeling.
AB  - Carboxymethyl cellulose (CMC) can facilitate in situ delivery of zero-valent iron
      (ZVI) nanoparticles in contaminated aquifer. This work investigated transport of
      CMC-stabilized ZVI nanoparticles (CMC-Fe) using column breakthrough experiments
      and model simulations. The nanoparticles (18.1+/-2.5 nm) were transportable
      through four saturated model porous media: coarse and fine glass beads, clean
      sand, and sandy soil. The transport data were interpreted using both classical
      filtration theory and a modified convection-dispersion equation with a first
      order removal rate law. At full breakthrough, a constant concentration plateau
      (Ce/C0) was reached, ranging from 0.99 for the glass beads to 0.69 for the soil.
      While Brownian diffusion was the predominant mechanism for particle removal in
      all cases, gravitational sedimentation also played an important role, accounting
      for 30% of the overall single-collector contact efficiency for the coarse glass
      beads and 6.7% for the soil. The attachment efficiency for CMC-Fe was found to be
      1-2 orders of magnitude lower than reported for ZVI nanoparticles stabilized with
      other commercial polymers. The particle removal and travel distance are strongly
      dependent on interstitial flow velocity, but only modestly affected by up to 40
      mM of calcium. Simulation results indicate that once delivered, 99% of the
      nanoparticles will be removed by the soil matrix within 16 cm at a groundwater
      flow velocity of 0.1 m/day, but may travel over 146 m at flow velocity of 61
      m/day.

PMID- 19383563
TI  - Association of trait-defined, eating-disorder sub-phenotypes with (biallelic and
      triallelic) 5HTTLPR variations.
AB  - CONTEXT: Efforts to classify eating-disordered individuals based on concurrent
      personality traits have consistently converged on a typology encompassing "over
      regulated", "dysregulated", and "low psychopathology" subgroups. In various
      populations, evidence has associated personality variations of an "over
      regulated/dysregulated" type with differences on serotonin-system indices, and
      specifically, with different loadings of serotonin transporter promoter
      regulatory region polymorphism (5HTTLPR) genotypes and alleles. We explored the
      extent to which an empirical, trait-defined typology of eating-disordered
      individuals coincided systematically with variations in 5HTTLPR, assayed using
      biallelic and triallelic models. METHOD: We tested 185 women with a DSM-IV eating
      disorder (108 with Bulimia Nervosa, 17 Anorexia Nervosa, and 60 an Eating
      Disorder Not Otherwise Specified) and 93 with no eating disorder on measures
      reflecting psychopathological traits and 5HTTLPR (biallelic and triallelic)
      genotypes and alleles. RESULTS: The highest-function, triallelic (L(A)/L(A))
      genotype occurred significantly more frequently among eating-disordered
      individuals than among controls. However, a more fine-grained analysis suggested
      that this association was attributable to the fact that, among eating-disordered
      participants, those displaying an "Inhibited/Compulsive" profile (derived using
      latent class analysis) were more likely than those of a "Dissocial/Impulsive" or
      a "Low Psychopathology" group to carry the triallelic 5HTTLPR gain-of-function
      L(A) allele and to be L(A)/L(A) homozygotes. DISCUSSION: This study's empirically
      derived classes coincide with interpretable differences on genetic indices
      associating an "Inhibited/Compulsive" group with 5HTTLPR gain-of-function
      genotypes (and alleles) that have elsewhere been linked to trait compulsivity.
      The findings, furthermore, suggest that 5HTTLPR, by influencing personality-trait
      manifestations may, in turn, influence eating-disorder risk and symptom
      expression.

PMID- 19383564
TI  - Rescue of internal initiation of translation by RNA complementation provides
      evidence for a distribution of functions between individual IRES domains.
AB  - Picornavirus RNAs initiate translation using an internal ribosome entry site
      (IRES)-dependent mechanism. The IRES element of foot-and-mouth disease virus
      (FMDV) is organized in domains, being different from each other in RNA structure
      and RNA-protein interaction. Wild-type transcripts provided in trans rescue
      defective FMDV IRES mutants. Complementation, however, was partial since
      translation efficiency of the mutant RNAs was up to 10% of the wild type IRES. We
      report here that mutations diminishing the RNA-RNA interaction capacity induced a
      decrease in IRES rescue. On the other hand, IRES transcripts bearing mutations
      that reorganize the RNA structure of the apical region of central domain,
      although weakly, complement defective IRES that are unable to interact with the
      initiation factor eIF4G in a separate domain. Together, these results suggest
      that IRES rescue may involve RNA-mediated contacts between defective elements,
      each carrying a defect in a separate domain but having the complementing one with
      the appropriate structural orientation and/or ribonucleoprotein composition. Our
      observations further support the essential role of the central domain of the FMDV
      IRES during protein synthesis and demonstrate that there is a division of
      functions between the IRES domains.

PMID- 19383565
TI  - Activation of the 2-5OAS/RNase L pathway in CVB1 or HAV/18f infected FRhK-4 cells
      does not require induction of OAS1 or OAS2 expression.
AB  - The latent, constitutively expressed protein RNase L is activated in
      coxsackievirus and HAV strain 18f infected FRhK-4 cells. Endogenous
      oligoadenylate synthetase (OAS) from uninfected and virus infected cell extracts
      synthesizes active forms of the triphosphorylated 2-5A oligomer (the only known
      activator of RNase L) in vitro and endogenous 2-5A is detected in infected cell
      extracts. However, only the largest OAS isoform, OAS3, is readily detected
      throughout the time course of infection. While IFNbeta treatment results in an
      increase in the level of all three OAS isoforms in FRhK-4 cells, IFNbeta
      pretreatment does not affect the temporal onset or enhancement of RNase L
      activity nor inhibit virus replication. Our results indicate that CVB1 and
      HAV/18f activate the 2-5OAS/RNase L pathway in FRhK-4 cells during permissive
      infection through endogenous levels of OAS, but contrary to that reported for
      some picornaviruses, CVB1 and HAV/18f replication is insensitive to this
      activated antiviral pathway.

PMID- 19383566
TI  - trans-Complementation of HBV rtM204I mutant replication by HBV wild-type
      polymerase.
AB  - The function of the hepatitis B virus (HBV) wild-type (WT) polymerase (pol)
      expressed alone or in the context of the intact genome when interacting with HBV
      rtM204I in HepG2 cells was compared. We show that WT pol expression from a
      packaging-defective RNA can complement defective rtM204I pol activity resulting
      in increased levels of HBV replicative intermediates (RI). Analysis of the
      genetically marked genomes showed that this restoration resulted from trans
      complementation, rather than recombination. In contrast, we demonstrate that
      enhanced levels of total HBV RI observed when cells were cotransduced with both
      WT and rtM204I baculoviruses were predominantly WT RI. In this case, WT pol was
      produced from a full-length pregenomic RNA (pgRNA). We conclude that the WT pol
      has the capacity to trans-complement the replication defect of rtM204I; however,
      when expressed from an authentic pgRNA, as in a mixed infection, pol may not
      trans-complement efficiently.

PMID- 19383567
TI  - Myocardium-targeted transplantation of mesenchymal stem cells by diagnostic
      ultrasound-mediated microbubble destruction improves cardiac function in
      myocardial infarction of New Zealand rabbits.
AB  - BACKGROUND: Therapeutic ultrasound-mediated microbubble destruction has been
      applied in the targeted delivery of genes, drugs and stem cells. We intended to
      study whether diagnostic US irradiating lipid-coated microbubble destruction
      combined with bone-marrow derived MSC infusion could enable the targeted delivery
      of MSCs into the myocardium and improve cardiac function of the myocardial
      infarction of New Zealand rabbits. METHODS: Diagnostic ultrasound was applied to
      the anterior chest for 10 min after intravenous injection of lipid-coated
      microbubble followed by infusion of BM-MSCs. Echocardiography, histological
      examination, and western blotting were performed 4 weeks after cell
      transplantation. RESULTS: The cardiac function (assessed by fractional shortening
      and ejection fraction) was markedly improved by US+Microbubble+MSC treatment. The
      number of capillaries stained by HE in US+Microbubble+MSC group (47+/-23) was
      much greater than that of the MSCs infusion group (26+/-7), US+Microbubble
      group(22+/-5) and PBS infusion group (19+/-10), P<0.01. US+Microbubble
      stimulation induced the expression of adhesion molecule (VCAM-1) in capillaries
      and enhanced the myocardial permeability of microvessels. US+Microbubble-mediated
      supply of MSCs increased the level of VEGF in ischemic myocardium. Area of
      cardiac fibrosis in the US+Microbubble+MSC group was significantly decreased by
      25.6%,40.1% and 46.8% when compared with MSC infusion group, US+Microbubble group
      and PBS infusion group, respectively. CONCLUSIONS: This non-invasive cell
      delivery system may be useful as a novel and efficient approach for angiogenic
      cell therapy to the infarcted myocardium.

PMID- 19383568
TI  - Characterization of cooperative effects in linear alpha-glycylglycine clusters.
AB  - The aspects of N-H...O=CNH, N-H...O=CO and C-H...O=CNH interactions are analyzed
      by applying ab initio and DFT methods as well as Bader theory. We investigated
      geometry, binding energies, (17)O, (15)N chemical shift tensors, and Atoms in
      Molecules (AIM) properties of alpha-glycylglycine (alpha-glygly) clusters, via
      MP2, B3LYP and PW91(XC) methods. Dimer stabilization energies and equilibrium
      geometries are studied in various levels of theory. MP2 and DFT calculations
      reveal that for alpha-glygly clusters, stability of N-H...O and C-H...O hydrogen
      bonds are enhanced significantly as a result of cooperativity effects.
      Furthermore, a covalent nature is also detected for some hydrogen bondings. The n
      dependent trend of (17)O and (15)N chemical shift tensors was reasonably
      correlated with cooperative effects in hydrogen-bond interactions. Regarding the
      various N-H...O=CNH, N-H...O=CO and C-H...O=CNH hydrogen bondings, capability of
      the alpha-glygly clusters for electron localization at the N-H...O and C-H...O
      bond critical points, depends on the cluster size. This leads to cooperative
      changes in the hydrogen-bond length and strength as well as (17)O and (15)N
      chemical shift tensors.

PMID- 19383569
TI  - Use of waste brick as a partial replacement of cement in mortar.
AB  - The aim of this study is to investigate the use of waste brick as a partial
      replacement for cement in the production of cement mortar. Clinker was replaced
      by waste brick in different proportions (0%, 5%, 10%, 15% and 20%) by weight for
      cement. The physico-chemical properties of cement at anhydrous state and the
      hydrated state, thus the mechanical strengths (flexural and compressive strengths
      after 7, 28 and 90 days) for the mortar were studied. The microstructure of the
      mortar was investigated using scanning electron microscopy (SEM), the
      mineralogical composition (mineral phases) of the artificial pozzolan was
      investigated by the X-ray diffraction (XRD) and the particle size distributions
      was obtained from laser granulometry (LG) of cements powders used in this study.
      The results obtained show that the addition of artificial pozzolan improves the
      grinding time and setting times of the cement, thus the mechanical
      characteristics of mortar. A substitution of cement by 10% of waste brick
      increased mechanical strengths of mortar. The results of the investigation
      confirmed the potential use of this waste material to produce pozzolanic cement.

PMID- 19383570
TI  - The effect of inertial loading on wrist postural tremor in essential tremor.
AB  - OBJECTIVES: Determine the effect of inertial loading on the strength of motor
      unit entrainment and the synergistic/competitive interaction between central and
      mechanical reflex tremor components in subjects with essential tremor (ET).
      METHODS: Twenty-three subjects with ET and 22 controls held their hand in an
      outstretched position while supporting sub-maximal loads (no-load, 5%, 15% and
      25% 1-repetition maximum). Hand postural tremor and wrist extensor neuromuscular
      activity were recorded. RESULTS: Inertial loading resulted in a reduction in
      postural tremor in all ET subjects. The largest reduction in tremor amplitude
      occurred between 5% and 15% loads, which was associated with spectral separation
      of the mechanical reflex and central tremor components in a large number of ET
      subjects. Despite an increase in overall neuromuscular activity with inertial
      loading, EMG tremor spectral power did not increase with loading. CONCLUSIONS:
      The effect of inertial loading on postural tremor amplitude appears to be
      mediated in large part by its effect on the interaction between mechanical reflex
      and central tremor components. Also, ET is associated with a constant absolute
      level of motor unit entrainment. SIGNIFICANCE: The amplitude of postural tremor
      is dependent on both central and peripheral factors, with proportionally greater
      motor unit entrainment occurring at low contraction intensities.

PMID- 19383571
TI  - Electrochemical properties of catechin at a single-walled carbon nanotubes
      cetylramethylammonium bromide modified electrode.
AB  - The electrochemical properties of catechin at single-walled carbon nanotubes
      (SWNTs)-cetylramethylammonium bromide (CTAB) modified glassy carbon electrodes
      (GCE) were investigated by cyclic voltammetry (CV) and differential pulse
      voltammetry (DPV). The SWNTs-CTAB film was characterized with transmission
      electron microscopy (TEM). A series of parameters including pH of supporting
      electrolyte, accumulation potential and accumulation time were optimized. There
      were three peaks of catechin at SWNTs-CTAB/GCE in the potential range of -0.4-1.0
      V in PBS (pH 7.0): a reversible pair of peaks and an irreversible peak of the
      anodic peak. The reductive peak current increased linearly with the concentration
      of catechin in the range from 3.72 x 10(-10) to 2.38 x 10(-9) M. The detection
      limit was 1.12 x 10(-10) M. The SWNTs-CTAB/GCE showed good stability and low
      detection limit, and could be applied to detect trace catechin.

PMID- 19383573
TI  - [From the metabolic syndrome to the concept of global cardiometabolic risk].
AB  - Although the clustering of cardiovascular risk factors is unquestionable, the
      clinical significance of the metabolic syndrome as a distinct entity has been
      debated in the past years. Recently, the term 'metabolic syndrome' has been
      replaced by 'global cardiometabolic risk' which implies cardiovascular risk
      factors beyond the metabolic syndrome. The metabolic syndrome can be frequently
      detected among people in western and developing countries affecting 25-30% of
      adult population, and its prevalence rate is increasing. Prospective studies show
      that the metabolic syndrome is a significant predictor of incident diabetes but
      has a weaker association with cardiovascular morbidity and mortality. At the same
      time the metabolic syndrome is inferior to established predicting models for
      either type 2 diabetes or cardiovascular disease.The underlying pathomechanism of
      the metabolic syndrome is still poorly understood. The role of insulin resistance
      -although not as a single factor--is still considered as a key component. In the
      last decade the importance of abdominal obesity has received increased attention
      but some studies, mainly in the Asian population, showed that central obesity is
      not an essential component of the syndrome. Regardless of the theoretical debates
      the practical implications are indisputable. The frequent clustering of
      hypertension, dyslipidaemia and glucose intolerance, that often accompanies
      central obesity, can not be ignored. Following the detection of one risk factor,
      the presence of other, traditional and non-traditional factors should be searched
      for, as the beneficial effect of intensive, target oriented, continuous treatment
      of metabolic and cardiovascular risk factors has been proven in both the short
      and long term.

PMID- 19383574
TI  - [Prevention and treatment of erectile dysfunction after radical prostatectomy].
AB  - Radical prostatectomy is the curative surgical management of organ confined
      prostate cancer. Erectile dysfunction may follow surgery as the most common
      complication decreasing the quality of life of the patient. Thanks to spreading
      PSA screening probability increases to detect prostate cancer in its early stage
      and so the expected number of surgery is increasing, too. Higher number of
      operation as well as surgery more frequently performed in younger age calls the
      attention to the importance of erectile dysfunction and its management. Nowadays
      the physiology of erectile dysfunction due to radical prostatectomy has been
      revealed, and as a consequence, the nerve sparing surgery for its prevention is
      already known. The paper presents the different kind of possible invasive and non
      invasive treatments of erectile dysfunction, and surveys their history and
      effectiveness. The erectile function of patients who underwent radical
      prostatectomy between 1998 and 2007 at the Department of Urology and Uro
      oncological Centre was assessed by IIEF- and MMM questionnaire and letters with
      questions of habit of medicine taking. The results show that 59% of patients who
      desire sexual activity are capable of it spontaneously or with medical
      management.

PMID- 19383575
TI  - [Nutrition in inflammatory bowel disease].
AB  - Aetiology of inflammatory bowel disease (IBD) is complex and probably
      multifactorial. Nutrition has been proposed to be an important aetiological
      factor for development of IBD. Several components of the diet (such as sugar,
      fat, fibre, fruit and vegetable, protein, fast food, preservatives etc.) were
      examined as possible causative agents for IBD. According to some researchers
      infant feeding (breast feeding) may also contribute to the development of IBD.
      Though the importance of environmental factors is evidenced by the increasing
      incidence in developed countries and in migrant population in recent decades, the
      aetiology of IBD remained unclear. There are many theories, but as yet no dietary
      approaches have been proved to reduce the risk of developing IBD. The role of
      nutrition in the management of IBD is better understood. The prevention and
      correction of malnutrition, the provision of macro- and micronutrients and
      vitamins and the promotion of optimal growth and development of children are key
      points of nutritional therapy. In active disease, the effective support of energy
      and nutrients is a very important part of the therapy. Natural and artificial
      nutrition or the combination of two can be chosen for supporting therapy of IBD.
      The author summarises the aetiological and therapeutic role of nutrition in IBD.

PMID- 19383576
TI  - [Heart rate variability analysis in sports].
AB  - Differences in the duration of the cycles reflects the balance of the sympathetic
      and parasympathetic influence on the heart. Variance in the heart rate correlates
      to the breathing cycle, to baroreflex sensitivity, to day and night alternations
      and to changes in the vegetative tone evoked by physical exercises. Analysis of
      the time and/or frequency power domain of the heart rate variance is expected to
      have diagnostic value in physiological and pathological situations as adaptation
      to training, overtraining, heart disease etc. Both time- and frequency domains
      reflect the same physiological phenomenon but from different point of view. Vagus
      tonus is reflected in the high frequency part of the range of variance, while an
      increased sympathetic tone enriches the low frequency part of the variations of
      the duration of the consecutive heart cycles. This technically simple and
      relatively inexpensive method has inspired a couple of clinical and sports
      medical studies. Certain tendencies seem to be clear, but for individual
      diagnosis or for prognosis the data must be treated very carefully.

PMID- 19383577
TI  - [Tribute to Dr. Istvan Meszaros--80 years of age].

PMID- 19383578
TI  - [Egeszsegpolitikai Szemle--a barely known medical journal].

PMID- 19383582
TI  - Preoperative oral pentoxifylline for management of cytokine reactions in cardiac
      surgery.
AB  - BACKGROUND: Cardiopulmonary bypass may lead to many inflammatory responses that
      may cause myocardial dysfunction after open heart surgery. We aimed to
      investigate the effect of preoperative pentoxifylline treatment to reduce the
      occurrence of cardiopulmonary bypass-induced inflammatory response. METHODS: In a
      prospective, randomized study, 40 patients undergoing coronary artery bypass
      graft surgery received either pentoxifylline (study group, n = 21) or not
      (control group, n = 19). Pretreatment with pentoxifylline (800 mg/day orally) was
      started 5 days before the operation. Blood samples for measurements of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8 from the arterial line, and
      venous blood samples for creatine kinase (CK) and CK isoenzyme fraction MB (CK
      MB) were taken in both groups at 5 different time points. Hemodynamic parameters
      were measured with the thermodilution technique. RESULTS: TNF-alpha, IL-6, and IL
      8 plasma levels increased in both groups after cardiopulmonary bypass, with a
      greater increase in the control group (P < .05). There were no significant
      differences between the groups for the values of CK-MB and hemodynamic
      parameters. CONCLUSIONS: We conclude that pretreatment with oral pentoxifylline
      before cardiac surgery inhibits proinflammatory cytokine release caused by
      cardiopulmonary bypass and has some beneficial effects in protecting the
      myocardium during the cardioplegic arrest period in open-heart surgery, without
      affecting postoperative hemodynamics.

PMID- 19383583
TI  - Lupus aortitis leading to aneurysmal dilatation in the aortic root and ascending
      aorta.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs,
      tissues, and cells undergo damage mediated by tissue-binding autoantibodies and
      immune complexes. We describe the case of a 23-year-old African American woman
      with a history of recurrent pneumonias. Computed tomography, magnetic resonance
      imaging (MRI), and echocardiographic evaluations, as well as clinical and
      laboratory findings, indicated a diagnosis of SLE with inflammatory aortitis
      secondary to SLE vasculitis. A repeat MRI revealed a rapidly expanding aortic
      root and ascending aorta that required prompt operative repair. The ascending
      aorta and aortic root were replaced with a mechanical valved conduit, and a
      coronary artery bypass to the posterior descending artery was performed because
      of related erosion into the intima of the right coronary ostium. The patient has
      done well postoperatively. Aortitis and aortic aneurysms are an uncommon
      manifestation of SLE, and a literature search revealed an apparent association
      between aortic aneurysms and steroid medications for SLE. This case is the first
      report of aortitis resulting in a nondissecting aortic root aneurysm in an SLE
      patient without a history of steroid use, indicating that all SLE patients,
      including those without a history of steroid use, require screening for aortic
      disease to improve surgical outcomes and to prevent fatal complications.

PMID- 19383584
TI  - Is interrupted inferior vena cava a risk factor in cases of bilateral
      bidirectional Glenn?
AB  - INTRODUCTION: Bilateral superior vena cava-to-pulmonary artery anastomoses are
      technically challenging. Bilateral superior vena cavae (SVCs) have been thought
      to be a risk factor for poor outcome in children needing single-ventricle
      palliation. METHODS: The files of forty children who underwent bilateral
      cavopulmonary anastomoses (CPAs) were reviewed. RESULTS: Forty patients (31 male,
      9 female) had bilateral bidirectional Glenn shunts in King Faisal Specialist
      Hospital and Research Center, Jeddah, in 7 years. Interrupted inferior vena cava
      (IIVC) was present in 8 patients. All IIVC cases featured a hypoplastic right
      ventricle. Twenty-four patients had a hypoplastic right ventricular morphology,
      and 16 patients had a hypoplastic left ventricular morphology. CONCLUSIONS: In
      single-ventricle anatomy, cases of a bilateral SVC are more often associated with
      an IIVC than a single SVC. Patients who undergo bilateral CPAs with an IIVC have
      a difficult early postoperative course. We should look for IIVC and either
      exclude or prove IIVC in cases of bilateral SVCs. Postoperative anticoagulation
      therapy in children with bilateral CPAs is important but should be investigated
      further.

PMID- 19383585
TI  - Postoperative pericardial effusion and posterior pericardiotomy, related or not?
AB  - INTRODUCTION: Large pericardial effusions after cardiac surgery develop in 30% of
      patients and reach their maximum size on approximately day 10 postoperatively.
      Tamponade develops in approximately 1% of patients with large pericardial
      effusions. Effusion may be prevented by posterior pericardiotomy, but its role
      and possible adverse consequences are controversial. We sought to further
      investigate the effectiveness of this technique. METHOD: This prospective
      randomized case-control study was carried out on 410 patients, mean age 68.4 +/-
      9.2 years, who underwent coronary artery bypass graft surgery alone or combined
      with valve surgery during the period between April 2005 and May 2006. A 4-cm
      longitudinal incision was made parallel and posterior to the phrenic nerve in the
      pericardiotomy group. Echocardiographic study was performed at the time of
      discharge and 15 and 30 days after surgery. RESULTS: After 15 and 30 days
      postsurgery, respectively, 178 (90.2%) and 192 (97%) of patients from the
      pericardiotomy group and none from the conventional group were free of effusion
      (P < .05). CONCLUSION: Posterior pericardiotomy is easy to perform and is a safe
      and effective means to prevent postoperative effusion and its early and delayed
      adverse consequences.

PMID- 19383586
TI  - Tentacles: a novel device for exposing the heart for the insertion of left apical
      assist device cannulae.
AB  - BACKGROUND: The implantation of ventricular assist devices is a well-established
      procedure for the treatment of imminent heart failure. The exact positioning of
      the left ventricular apical inflow cannula is crucial, because inflow
      restrictions might occur when the cannula is placed too close to the
      interventricular septum or a papillary muscle. We report a novel technique using
      the Tentacles 3-point fixation device for the exposure of the left ventricular
      apex during ventricular fibrillation under cardiopulmonary bypass. METHODS: We
      used the Tentacles, a device originally designed for positioning the heart during
      off-pump coronary artery bypass grafting, for implantation of a biventricular
      Berlin Heart Excor in a 64-year-old man. The procedure was successful and
      echocardiographic examinations documented the exact placement of the left
      ventricular cannula. RESULTS AND CONCLUSION: Our new technique ensures a very
      precise insertion of apical cannulae, because the left ventricular shape and
      filling are not impaired.

PMID- 19383587
TI  - Hemoptysis as a presenting symptom of a distal aortic arch aneurysm and its
      repair via an L-shaped thoracotomy.
AB  - A 61-year-old man presented with multiple episodes of hemoptysis. A computed
      tomography scan revealed a 70-mm saccular aneurysm of the distal aortic arch.
      During a surgical repair via a midline sternotomy and a left thoracotomy, a
      saccular aneurysm was found to protrude into the lung, which had chronically
      healed. The patient underwent replacement of the Dacron graft, and he recovered
      well postoperatively. This experience prompted us to report the findings of this
      unique case.

PMID- 19383588
TI  - Mitroflow bioprosthesis stent deformation: a rare cause of early prosthetic
      stenosis.
AB  - We report the case of a severe prosthetic aortic stenosis in a 61-year-old male
      patient with an aortic Mitroflow LF bioprosthesis (Sorin Group) at early (6
      months) postoperative echocardiographic follow-up. At reintervention, we found
      significant stent deformation, asymmetric orientation of the posts, and
      subsequent central kinking and prolapse of one leaflet. Maldistribution of
      pledgeted mattress sutures over the flexible stent was found to be the origin of
      its permanent deformation. Simple technical preventive strategies of this
      previously unreported complication are suggested.

PMID- 19383589
TI  - Comparison of unilateral antegrade cerebral perfusion at 16 degrees C and 22
      degrees C systemic temperature.
AB  - OBJECTIVES: Unilateral antegrade cerebral perfusion can be performed with minimal
      manipulations to arch arteries, but whether it provides adequate brain perfusion
      remains unclear. Some authors believe that this technique can be inadequate
      without deep hypothermia. We investigated the reliability of unilateral cerebral
      perfusion at 22 degrees C hypothermia and the advantages of avoiding deep
      hypothermia. METHODS: Study participants were 55 patients who underwent surgery
      with unilateral cerebral perfusion. Patients were divided into 2 groups; 18
      patients underwent surgery at 16 degrees C hypothermia (group I) and 37 patients
      at 22 degrees C hypothermia (group II). The mean age of the patients was 59 +/-
      10 years in group I and 55 +/- 14 years in group II. Supracoronary ascending
      aorta replacement was performed in 25 and hemiarch replacement in 15 patients.
      Nine patients underwent surgery for a Bentall procedure. Total arch replacement
      was performed in 4 patients and total thoracic aorta replacement in 2 patients.
      RESULTS: The hospital mortality was 11% in group I and 5.4% in group II (P =
      .59). Transient neurologic deficits were not detected in any of the patients. The
      rate of permanent neurologic deficits was 5.9% in group I and 2.8% in group II (P
      = .54). Although mean aortic cross-clamp and antegrade cerebral perfusion times
      were not significantly different, mean cardiopulmonary bypass time was longer in
      group I than group II (174 +/- 38 vs 142 +/- 37 minutes, P = .005). Postoperative
      bleeding, blood product usage, serum creatinine and hepatic enzyme level changes,
      inotrope usage, and arrhythmia occurrence were not different between the 2
      groups. Mean mechanical ventilation time was longer in group I than group II (24
      +/- 17 vs 16 +/- 6 hours, P = .02). CONCLUSIONS: Unilateral antegrade cerebral
      perfusion at 22 degrees C systemic hypothermia appears to be safe and reliable
      for brain protection. Advantages of this technique are avoidance of deep
      hypothermia and reduced cardiopulmonary bypass and mechanical ventilation times
      in patients undergoing aortic surgery.

PMID- 19383590
TI  - Benefits of the preemptive intra-aortic balloon pump: an audit of practice in a
      regional cardiothoracic center.
AB  - BACKGROUND: Recent evidence suggests that preemptive use of an intra-aortic
      balloon pump (IABP) is associated with better outcomes in high-risk patients
      undergoing cardiac surgery. This retrospective study compares preemptive
      (planned) use of the IABP to emergency (unplanned) use in a regional
      cardiothoracic center. METHODS: All patients who required an IABP from February
      2003 to June 2006 were identified from theater records. The collected data
      included patient demographics, preoperative state, operative details, morbidity
      due to the IABP, and operative mortality. Patients were divided into 2 groups:
      planned use (preoperative plus elective intraoperative) and unplanned use
      (postoperative plus emergency intraoperative). Preoperative mortality risk was
      calculated with the logistic EuroSCORE. RESULTS: We identified 135 patients (75%
      male). There were no significant differences between the groups with respect to
      age, preoperative state, operation type, logistic EuroSCORE, or myocardial
      ischemia time. The 2 groups showed a significant difference in mortality: planned
      IABP insertion, 17%; unplanned insertion, 45% (P = .001). A multivariate analysis
      of the study population showed the logistic EuroSCORE (odds ratio, 0.974; 95%
      confidence interval, 0.950-0.998; P = .035) and timing of IABP use (odds ratio,
      4.728; 95% confidence interval, 1.932-11.566; P = .001) to be independent
      predictors of mortality. CONCLUSION: Preemptive use of the IABP in this patient
      cohort was associated with a 50% advantage in mortality compared with emergency
      IABP use. The logistic EuroSCORE may be used preoperatively to guide IABP use.
      Complications are rare and can be treated successfully. The risk-to-benefit ratio
      of preemptive IABP use is low in this cohort of patients.

PMID- 19383591
TI  - Continuous arterial pressure waveform analysis accurately detects cardiac output
      in cardiac surgery: a prospective comparison with thermodilution,
      echocardiography, and magnetic resonance techniques.
AB  - OBJECTIVE: The aim of this study was to compare the accuracy of cardiac output
      (CO) measurements of noninvasive continuous arterial pressure waveform analysis,
      thermodilution technique and echocardiography with magnetic resonance (MRI)
      imaging. METHODS: Eleven patients who underwent coronary bypass surgery under
      cardiopulmonary bypass were prospectively enrolled in this study in 2008.
      Repeated arterial pressure based, thermodilution, echocardiography, and MRI
      cardiac output measurements were performed at the postoperative 24th hour.
      RESULTS: Mean CO values were 5.58 +/- 0.98, 5.97 +/- 0.8, 5.31 +/- 0.52, and 5.32
      +/- 0.92 measured with MRI, echocardiography, arterial pressure waveform
      analysis, and thermodilution techniques, respectively. Bland-Altman analysis
      showed good overall agreement between the MRI vs arterial waveform analysis and
      MRI vs thermodilution; values for bias +/- SD were -0.27 +/- 1.06 (95% confidence
      interval [CI] [-2.3 to 1.8]; P = .42) and -0.26 +/- 0.89 (95% CI [-2.0 to 1.5]; P
      = .34), respectively. Poor agreement was defined between MRI and
      echocardiography: bias +/- SD, 0.39 +/- 1.28 (95% CI [-2.1 to 2.9]; P = .34).
      CONCLUSIONS: Arterial pressure-based and thermodilution CO measurement systems
      yielded results comparable to those obtained with cardiac MRI assessment after
      cardiac surgery. Arterial pressure wave-form analysis systems for CO measurement
      may be feasible, noninvasive methods for use in cardiac surgery.

PMID- 19383592
TI  - Gastrointestinal ischemia related mortality in patients undergoing off- or on
      pump coronary artery bypass grafting.
AB  - OBJECTIVE: Gastrointestinal ischemia (GII) after heart surgery is a rare but
      devastating condition. The aim of this study was to compare the occurrence of GII
      after coronary artery bypass grafting (CABG) performed off-pump (OPCAB) vs on
      pump (ONCAB). METHODS: We retrospectively evaluated 2625 adult patients who
      underwent isolated coronary artery surgery during a 6-year period. The OPCAB
      group included 658 patients and the ONCAB group 1967 patients. Patients were
      evaluated, and GII, morbidity, and mortality in the 2 groups were compared.
      RESULTS: GII developed in 0.4% (7 of 1967) patients in the ONCAB group and in
      0.2% (1 of 658) patients in the OPCAB group (P = .28). Mortality rates due to GII
      were 0.2% (4 of 1967) in the ONCAB group, and no deaths occurred in the OPCAB
      group (P < .04). Postoperative atrial fibrillation incidence with GII was 100% (7
      of 7) in ONCAB group and 0% (0 of 1) in the OPCAB group (P < .01). CONCLUSIONS:
      Compared to ONCAB, the OPCAB procedure has lower GII related mortality rates,
      which is an important cause of morbidity and mortality in the postoperative
      period of CABG surgery.

PMID- 19383593
TI  - Investigation on the structure of ventricular mass using magnetic resonance
      diffusion tensor imaging.
AB  - OBJECTIVE: The 3-dimensional arrangement of the ventricular mass remains
      controversial. In this study, we used magnetic resonance diffusion tensor imaging
      (MRDTI) in an attempt to determine whether the ventricular mass is arranged in
      the form of a helical ventricular myocardial band (HVMB) and what the geometrical
      features of the HVMB are in postmortem pig hearts. MATERIALS AND METHODS: Ten pig
      hearts were harvested from the slaughterhouse, and their whole-body MR images
      were obtained. The data were obtained via DTI by single-shot echo planar imaging
      and sensitivity encoding. The pig hearts were scanned with single-shot echo
      planar imaging and sensitivity-encoding scans (TE/TRZ78.5/10000 ms) with
      diffusion-sensitized gradients (b = 800 s/mm2) along 6 directions. Color-coded
      imaging and fiber-tracking techniques were used to investigate the arrangement of
      the fibers of ventricular mass on a GE Healthcare Advantage Workstation
      (Microsoft Windows). RESULTS: Color-coded images showed that the ventricular wall
      in each section was uniformly divided into 3 layers (subendocardial, middle, and
      subepicardial) in all samples. Fiber tracking showed that the subendocardial
      layer ran obliquely from base to apex, turned a circle, and transformed into the
      middle layer at the apex, and then ran obliquely upward. The ventricular mass was
      arranged in the form of double-helical coils. The crossing angle between
      subendocardial layer and middle layer was nearly vertical. CONCLUSION: Results of
      our investigation with MRDTI support the theory of Torrent-Guasp et al that the
      ventricular mass is arranged in the form of an HVMB.

PMID- 19383594
TI  - Cardioscopic tricuspid valve repair in a beating ovine heart.
AB  - BACKGROUND: Open heart surgery is commonly associated with cardiopulmonary bypass
      and cardioplegic arrest. The attendant risks of cardiopulmonary bypass may be
      prohibitive in high-risk patients. We present a novel endoscopic technique of
      performing tricuspid valve repair without cardiopulmonary bypass in a beating
      ovine heart. METHODS: Six sheep underwent sternotomy and creation of a right
      heart shunt to eliminate right atrial and right ventricular blood for clear
      visualization. The superior vena cava, inferior vena cava, pulmonary artery, and
      coronary sinus were cannulated, and the blood flow from these vessels was shunted
      into the pulmonary artery via a roller pump. The posterior leaflet of the
      tricuspid valve was partially excised to create tricuspid regurgitation, which
      was confirmed by Doppler echocardiography. A 7.0-mm fiberoptic videoscope was
      inserted into the right atrium to visualize the tricuspid valve. Under
      cardioscopic vision, an endoscopic needle driver was inserted into the right
      atrium, and a concentric stitch was placed along the posterior annulus to
      bicuspidize the tricuspid valve. Doppler echocardiography confirmed reduction of
      tricuspid regurgitation. RESULTS: All animals successfully underwent and
      tolerated the surgical procedure. The right heart shunt generated a bloodless
      field, facilitating cardioscopic tricuspid valve visualization. The endoscopic
      stitch resulted in annular plication and functional tricuspid valve
      bicuspidization, significantly reducing the degree of tricuspid regurgitation.
      CONCLUSION: Cardioscopy enables less invasive, beating-heart tricuspid valve
      surgery in an ovine model. This technique may be useful in performing right heart
      surgery without cardiopulmonary bypass in high-risk patients.

PMID- 19383595
TI  - Does the circadian rhythm of melatonin affect ischemia-reperfusion injury after
      coronary artery bypass grafting?
AB  - BACKGROUND: Melatonin is a potent scavenger of free radicals and an antioxidant.
      We studied the relationship between the protective effect of melatonin against
      ischemia-reperfusion injury (IRI) during cardiopulmonary bypass, the plasma level
      of melatonin, and the time of surgery. METHODS: Forty patients who were to
      undergo elective coronary artery bypass grafting (CABG) were divided into 2
      groups, those who underwent their operations at 8 AM (group I; n = 20) and those
      who underwent their operations at 1 PM (group II; n = 20). The operations were
      carried out by the same surgical team and with the same standard surgical
      technique. Blood samples were collected before the operation (T1), when the
      aortic cross-clamp was removed (T2), and at 4 hours (T3) and 24 hours (T4) after
      the operation. RESULTS: Preoperative plasma levels of melatonin were
      substantially higher in group I than in group II. Intraoperative and
      postoperative melatonin levels were also significantly higher in patients who
      underwent their operations in the morning. The 2 groups had similar preoperative
      levels of intercellular adhesion molecule 1 and interleukin 8; however,
      intraoperative and postoperative values were lower in group I for all samples.
      This difference was statistically significant for both markers. Plasma levels of
      lactate dehydrogenase were significantly lower in group I. The 2 groups had
      similar aortic cross-clamp and cardiopulmonary bypass times. Preoperative and
      postoperative troponin I levels were lower in group I than in group II, but these
      differences were not statistically significant. The 2 groups showed no
      significant differences in plasma creatine kinase MB levels for either
      preoperative or postoperative measurements. CONCLUSION: High plasma levels of
      melatonin may be directly related to low levels of IRI markers. Melatonin may
      have a protective effect against IRI in CABG. This effect seems to be directly
      correlated with the plasma levels of melatonin and inversely related with light.
      If melatonin protects myocardium from IRI, additional studies may be planned for
      the preoperative use of melatonin in patients with coronary artery disease to
      improve myocardial protection.

PMID- 19383596
TI  - Occupational exposure of UK adults to extremely low frequency magnetic fields.
AB  - BACKGROUND: Occupational exposure to extremely low frequency (ELF) magnetic
      fields (MF) in the UK general population is poorly documented. AIMS: To assess
      levels of occupational exposure to ELF MF in the UK and evaluate the use of a
      rigid job-exposure matrix (JEM) to assign exposures to subjects in the UK Adult
      Brain Tumour Study (UKABTS). METHODS: Personal ELF MF measurements were carried
      out. Exposure traces were divided into occupational, travel and elsewhere
      periods, under differing exposure metrics. Exposure was classified by Standard
      Occupational Classification (2000), Standard Industrial Classification (1997),
      and a combined occupation-industry classification. Statistical analyses (mixed
      effects model) determined the contribution of occupational exposure to the 24 h
      cumulative exposure and the contribution of occupation and industry to total
      variance. RESULTS: Data were obtained from 317 individuals, comprising UKABTS
      subjects (n = 192), occupational proxies for UKABTS subjects (n = 101) and
      "interest" readings (n = 24). 236 individuals provided occupational data covering
      117 different occupations. Average exposure was significantly higher at work than
      at home. Elevated average occupational exposure was found for welding trades,
      printers, telephonists and filing and other records assistants. The
      discrimination of a rigid JEM based on occupation can be improved by linking the
      classification with industry and by the use of contextual information.
      CONCLUSIONS: This report substantially expands information on adult exposure to
      ELF MF in the UK. The accuracy of exposure assessments based solely on job codes
      is improved by linking with either industry code or contextual knowledge of
      equipment and of power lines or substations in the work environment.

PMID- 19383597
TI  - Mycoplasma genitalium compared to chlamydia, gonorrhoea and trichomonas as an
      aetiological agent of urethritis in men attending STD clinics.
AB  - OBJECTIVES: To investigate prevalence of Mycoplasma genitalium, Chlamydia
      trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in men, frequency of
      co-infections, and association of organisms with urethritis in men. METHODS: This
      was a cross-sectional study of 290 men (age range 19-34 years) attending
      Baltimore City STD clinics. M genitalium, C trachomatis, N gonorrhoeae and T
      vaginalis, during 2004 were detected using nucleic acid amplification tests
      (NAATs) (153 with urethritis and 137 without urethritis). Demographic
      characteristics and risk factors were ascertained. RESULTS: The overall
      prevalences of infection with C trachomatis, N gonorrhoeae, T vaginalis and M
      genitalium were 20.3%, 12.8%, 3.4% and 15.2%, respectively. Prevalences in men
      with urethritis were 32.7%, 24.2%, 5.2% and 22.2% for C trachomatis, N
      gonorrhoeae, T vaginalis and M genitalium, respectively. Percentages of co
      infections were high. All men with N gonorrhoeae had urethritis. C trachomatis
      and M genitalium were found to be significantly associated with urethritis in
      univariate analysis and in multiple logistic regression analysis. CONCLUSION: The
      association of M genitalium with urethritis in this study provides confirmation
      of the importance of screening men for M genitalium as a cause of non-gonococcal
      urethritis and supports treatment considerations for urethritis for agents other
      than gonococci and chlamydia.

PMID- 19383598
TI  - Epidemiology and clinical presentation of gonorrhoea in England and Wales:
      findings from the Gonococcal Resistance to Antimicrobials Surveillance Programme
      2001-2006.
AB  - OBJECTIVE: To analyse the enhanced data for gonorrhoea cases in England and Wales
      collected by the Gonococcal Resistance to Antimicrobials Surveillance Programme
      (GRASP) to better inform health policy and targeted interventions. METHODS: GRASP
      data obtained annually from sentinel genitourinary medicine (GUM) clinics between
      June to August during 2001-6 were analysed. RESULTS: A total of 12 282 cases of
      gonorrhoea were reported during the study period, with a decline over time
      primarily in heterosexual patients of black ethnicity. 73% of women, 47% of
      heterosexual men and 22% of men who have sex with men (MSM) were aged under 25.
      Most infected women reported a single sexual partner in the previous 3 months,
      whereas most heterosexual men and MSM reported two or more partners. A history of
      gonorrhoea was reported by 42% of MSM, 30% of heterosexual men and 20% of women.
      Excluding HIV, women were more likely than men to have a concurrent STI at
      diagnosis, most commonly chlamydia (50% vs 27% p<0.0005). Rectal gonococcal
      infections were reported in 35% and HIV co-infection in 31% of MSM. Compared to
      HIV negative MSM, those co-infected with HIV were older (median 35 years vs 28
      years) and were more likely to attend a London site (70% vs 52%, p<0.0005); have
      a concurrent sexually transmitted infection (STI) (28% vs 20%, p = 0.002); have a
      history of gonorrhoea (66% vs 36%, p<0.0005) and have more sexual partners
      (average 6.8 vs 4.3). CONCLUSION: Gonorrhoea is concentrated within specific
      groups who are at high risk of repeat infections and concurrent STIs including
      HIV. Targeted interventions of proved effectiveness are urgently required.

PMID- 19383599
TI  - Combined trabeculectomy and cataract extraction versus trabeculectomy alone in
      primary angle-closure glaucoma.
AB  - AIMS: To compare the long-term efficacy and safety of combined trabeculectomy and
      cataract extraction versus trabeculectomy alone in primary angle-closure glaucoma
      (PACG). METHODS: Hospital files were retrospectively examined for 99 Chinese PACG
      patients; 75 patients underwent combined surgery and 24 underwent trabeculectomy
      alone. Success rates were assessed with the Kaplan-Meier survival analysis. The
      main outcome was the complete success rate defined as either a >20% reduction in
      intraocular pressure (IOP) or an IOP that remained below 15 mm Hg, with no
      medications required. RESULTS: Patients in the combined group and trabeculectomy
      group had a mean follow-up period of 25.8 (SD 10.8) months and 31.4 (8.9) months,
      respectively. Survival analysis showed that the complete success rate at 3 years
      was 56% in the combined group and 54% in the trabeculectomy group (p = 0.903).
      There were no significant differences between groups in either IOP or the number
      of glaucoma medications throughout the 3-year follow-up. The incidences of
      postoperative complications were similar between groups (p = 0.232). No
      additional IOP-lowering surgical procedures were required in the combined group,
      while 13 (54%) eyes in the trabeculectomy group required either cataract
      extraction or further IOP-lowering surgical procedures (p <0.001). CONCLUSION: In
      patients with PACG, the long-term IOP-lowering effect and surgical complications
      of combined trabeculectomy and cataract extraction are comparable with those of
      trabeculectomy alone. However, the combined surgery incurred fewer subsequent
      surgical interventions.

PMID- 19383600
TI  - ART and major structural birth defects in the United States.

PMID- 19383601
TI  - ATP-dependent proteases differ substantially in their ability to unfold globular
      proteins.
AB  - ATP-dependent proteases control the concentrations of hundreds of regulatory
      proteins and remove damaged or misfolded proteins from cells. They select their
      substrates primarily by recognizing sequence motifs or covalent modifications.
      Once a substrate is bound to the protease, it has to be unfolded and translocated
      into the proteolytic chamber to be degraded. Some proteases appear to be
      promiscuous, degrading substrates with poorly defined targeting signals, which
      suggests that selectivity may be controlled at additional levels. Here we compare
      the abilities of representatives from all classes of ATP-dependent proteases to
      unfold a model substrate protein and find that the unfolding abilities range over
      more than 2 orders of magnitude. We propose that these differences in unfolding
      abilities contribute to the fates of substrate proteins and may act as a further
      layer of selectivity during protein destruction.

PMID- 19383602
TI  - Inhibition of p66ShcA longevity gene rescues podocytes from HIV-1-induced
      oxidative stress and apoptosis.
AB  - Glomerular visceral epithelial cells (podocytes) play a critical role in the
      pathogenesis of human immunodeficiency virus (HIV)-associated nephropathy. A key
      question concerns the mechanism(s) by which the HIV-1 genome alters the phenotype
      of the highly specialized, terminally differentiated podocytes. Here, using an in
      vitro system of conditionally immortalized differentiated human podocytes
      (CIDHPs), we document a pivotal role for the p66ShcA protein in HIV-1-induced
      reactive oxygen species generation and CIDHP apoptosis. CIDHP transfected with
      truncated HIV-1 construct (NL4-3) exhibit increased reactive oxygen species
      metabolism, DNA strand breaks, and a 5-fold increase in apoptosis, whereas the
      opposite was true for NL4-3/CIDHP co-transfected with mu-36p66ShcA (micro-36)
      dominant negative expression vector or isoform-specific p66-small interfering
      RNA. Phosphorylation at Ser-36 of the wild type p66ShcA protein, required for
      p66ShcA redox function and inhibition of the potent stress response regulator
      Foxo3a, was unchanged in micro-36/NL4-3/CIDHP but increased in NL4-3/CIDHP. Acute
      knockdown of Foxo3a by small interfering RNA induced a 50% increase in micro
      36/NL4-3/CIDHP apoptosis, indicating that Foxo3a-dependent responses promote the
      survival phenotype in micro-36 cells. We conclude that inhibition of p66ShcA
      redox activity prevents generation of HIV-1 stress signals and activation of the
      CIDHP apoptosis program.

PMID- 19383603
TI  - Chaperones of F1-ATPase.
AB  - Mitochondrial F(1)-ATPase contains a hexamer of alternating alpha and beta
      subunits. The assembly of this structure requires two specialized chaperones,
      Atp11p and Atp12p, that bind transiently to beta and alpha. In the absence of
      Atp11p and Atp12p, the hexamer is not formed, and alpha and beta precipitate as
      large insoluble aggregates. An early model for the mechanism of chaperone
      mediated F(1) assembly (Wang, Z. G., Sheluho, D., Gatti, D. L., and Ackerman, S.
      H. (2000) EMBO J. 19, 1486-1493) hypothesized that the chaperones themselves look
      very much like the alpha and beta subunits, and proposed an exchange of Atp11p
      for alpha and of Atp12p for beta; the driving force for the exchange was expected
      to be a higher affinity of alpha and beta for each other than for the respective
      chaperone partners. One important feature of this model was the prediction that
      as long as Atp11p is bound to beta and Atp12p is bound to alpha, the two F(1)
      subunits cannot interact at either the catalytic site or the noncatalytic site
      interface. Here we present the structures of Atp11p from Candida glabrata and
      Atp12p from Paracoccus denitrificans, and we show that some features of the Wang
      model are correct, namely that binding of the chaperones to alpha and beta
      prevents further interactions between these F(1) subunits. However, Atp11p and
      Atp12p do not resemble alpha or beta, and it is instead the F(1) gamma subunit
      that initiates the release of the chaperones from alpha and beta and their
      further assembly into the mature complex.

PMID- 19383604
TI  - The butyrylcholinesterase K variant confers structurally derived risks for
      Alzheimer pathology.
AB  - The K variant of butyrylcholinesterase (BChE-K, 20% incidence) is a long debated
      risk factor for Alzheimer disease (AD). The A539T substitution in BChE-K is
      located at the C terminus, which is essential both for BChE tetramerization and
      for its capacity to attenuate beta-amyloid (Abeta) fibril formation. Here, we
      report that BChE-K is inherently unstable as compared with the "usual" BChE (BChE
      U), resulting in reduced hydrolytic activity and predicting prolonged
      acetylcholine maintenance and protection from AD. A synthetic peptide derived
      from the C terminus of BChE-K (BSP-K), which displayed impaired intermolecular
      interactions, was less potent in suppressing Abeta oligomerization than its BSP-U
      counterpart. Correspondingly, highly purified recombinant human rBChE-U monomers
      suppressed beta-amyloid fibril formation less effectively than dimers, which also
      protected cultured neuroblastoma cells from Abeta neurotoxicity. Dual activity
      structurally derived changes due to the A539T substitution can thus account for
      both neuroprotective characteristics caused by sustained acetylcholine levels and
      elevated AD risk due to inefficient interference with amyloidogenic processes.

PMID- 19383605
TI  - Discovery and characterization of a small molecule inhibitor of the PDZ domain of
      dishevelled.
AB  - Dishevelled (Dvl) is an essential protein in the Wnt signaling pathways; it uses
      its PDZ domain to transduce the Wnt signals from the membrane receptor Frizzled
      to downstream components. Here, we report identifying a drug-like small molecule
      compound through structure-based ligand screening and NMR spectroscopy and show
      the compound to interact at low micromolar affinity with the PDZ domain of Dvl.
      In a Xenopus testing system, the compound could permeate the cell membrane and
      block the Wnt signaling pathways. In addition, the compound inhibited Wnt
      signaling and reduced the levels of apoptosis in the hyaloid vessels of eye.
      Moreover, this compound also suppressed the growth of prostate cancer PC-3 cells.
      These biological effects suggest that by blocking the PDZ domain of Dvl, the
      compound identified in our studies effectively inhibits the Wnt signaling and
      thus provides a useful tool for studies dissecting the Wnt signaling pathways.

PMID- 19383606
TI  - State-stabilizing Interactions in Bacterial Mechanosensitive Channel Gating and
      Adaptation.
AB  - We outline several principles that we believe define the gating of two bacterial
      mechanosensitive channels, MscL and MscS. Serving as turgor regulators in
      bacteria and other walled cells, these molecules are tangible models for studying
      conformational transitions in membrane proteins driven directly by membrane
      tension. MscL, a compact pentamer, reversibly opens a gigantic 30-A pore at near
      lytic tensions. MscS, a heptameric complex, exhibits transient activation of a
      smaller pore at moderate tensions, thereby entering a tension-insensitive
      inactivated state. By comparing the structures and predicted transitions in these
      channels, we concluded that opening is commonly achieved through tilting and
      outward motion of the pore-lining helices, which is kinetically limited by
      hydration of the pore. The intricate adaptive behavior in MscS appears to depend
      on specific interhelical associations and the flexibility of the pore-lining
      helices. We discuss physical factors that may direct the transitions and
      stabilize main functional states in these channels.

PMID- 19383607
TI  - The urokinase plasminogen activator receptor promotes efferocytosis of apoptotic
      cells.
AB  - The urokinase receptor (uPAR), expressed on the surface of many cell types,
      coordinates plasmin-mediated cell surface proteolysis for matrix remodeling and
      promotes cell adhesion by acting as a binding protein for vitronectin. There is
      great clinical interest in uPAR in the cancer field as numerous reports have
      demonstrated that up-regulation of the uPA system is correlated with malignancy
      of various carcinomas. Using both stable cell lines overexpressing uPAR and
      transient gene transfer, here we provide evidence for a non-reported role of uPAR
      in the phagocytosis of apoptotic cells, a process that has recently been termed
      efferocytosis. When uPAR was expressed in human embryonic kidney cells, hamster
      melanoma cells, or breast cancer cells (BCCs), there was a robust enhancement in
      the efferocytosis of apoptotic cells. uPAR-expressing cells failed to stimulate
      engulfment of viable cells, suggesting that uPAR enhances recognition of one or
      more determinant on the surface of the apoptotic cell. uPAR-mediated engulfment
      was not inhibited by expression of mutant beta5 integrin, nor was alphavbeta5
      integrin-mediated engulfment modulated by cleavage of uPAR by
      phosphatidylinositol-specific phospholipase C. Further, we found that the more
      aggressive BCCs had a higher phagocytic capacity that correlated with uPAR
      expression and cleavage of membrane-associated uPAR in MDA-MB231 BCCs
      significantly impaired phagocytic activity. Because efferocytosis is critical for
      the resolution of inflammation and production of anti-inflammatory cytokines,
      overexpression of uPAR in tumor cells may promote a tolerogenic microenvironment
      that favors tumor progression.

PMID- 19383609
TI  - Severe back pain in a hemodialysis patient.

PMID- 19383608
TI  - Intracellular trypsin induces pancreatic acinar cell death but not NF-kappaB
      activation.
AB  - Premature intracellular activation of the digestive enzyme trypsinogen is
      considered to be the initiating event in pancreatitis. However, the direct
      consequences of intracellular trypsin activity have not previously been examined.
      In the current study, a mutant trypsinogen (paired basic amino acid cleaving
      enzyme (PACE)-trypsinogen), which is activated intracellularly by the endogenous
      protease PACE, was developed. This new construct allowed for the first time
      direct examination of the effects of intracellular trypsin on pancreatic acinar
      cells. We found that PACE-trypsinogen was expressed in the secretory pathway and
      was activated within acinar cells. Expression of PACE-trypsinogen induced
      apoptosis of HEK293 cells and pancreatic acinar cells, as indicated by histology,
      DNA laddering, PARP cleavage, and caspase-3 activation. Cell death was blocked by
      the trypsin inhibitor Pefabloc but not by the pancaspase inhibitor
      benzyloxycarbonyl-VAD, indicating that caspase-independent pathways were also
      involved. However, intracellular trypsin had no significant effect on the
      activity of the proinflammatory transcription factor NF-kappaB. In contrast,
      extracellular trypsin caused cell damage and dramatically increased NF-kappaB
      activity. These data indicate that localization of active trypsin determines its
      effects on pancreatic acinar cells. This new model will greatly improve our
      understanding of the role of active trypsin in pancreatitis and its associated
      inflammatory response.

PMID- 19383610
TI  - The internist's role in treating hypertension in hemodialysis patients.
AB  - Hypertension in hemodialysis patients is typically treated with a combination of
      volume removal with dialysis--although limited by current dialysis paradigms--and
      hypertension medications. Unfortunately, most patients treated in this manner
      remain hypertensive. This contrasts with superior results obtained in clinical
      studies in which salt restriction and augmented dialytic volume removal
      normalized blood pressure without requiring medicines. These results are
      consistent with the role of excess volume as the main etiology of hypertension in
      end-stage renal disease (ESRD). Interdialytic blood pressure is now recognized as
      important to patient prognosis. These measurements are frequently obtained by
      internists at office visits. Internists and nephrologists should address both
      peri-dialysis and interdialysis hypertension in a collaborative manner. This
      strategy should focus on, as much as reasonably possible, salt restriction and
      dialytic volume removal rather than hypertension medicines.

PMID- 19383611
TI  - Presentations and outcomes of neurosarcoidosis: a study of 54 cases.
AB  - OBJECTIVE: To report on the clinical presentations, laboratory abnormalities,
      treatment and outcomes in 54 patients with neurosarcoidosis (NS). BACKGROUND:
      Sarcoidosis is an inflammatory granulomatous disease affecting multiple organ
      systems. Neurosarcoidosis (CNS involvement) is seen in approximately 25% of
      patients with systemic sarcoidosis, although it is subclinical in most of these
      cases. Because of its rarity, exposure of neurologists to the clinical spectrum
      of NS is limited to case reports or short case series. PATIENTS AND METHODS: A
      database of 3900 patients treated at the Vanderbilt Multiple Sclerosis Clinic
      between 1995 and 2008 was searched for 'neurosarcoidosis', 'neurosarcoid',
      'sarcoidosis' and 'sarcoid'. Of the 162 patient records that were retrieved, 54
      patients were found to meet the criteria for definite, probable or possible
      neurosarcoidosis and were reviewed, including their clinical presentation,
      Cerebrospinal fluid (CSF) findings, Magnetic resonance imaging (MRIs), biopsy
      results, treatment, and where available, outcomes 4 months to 20 years after
      onset of the presenting illness. RESULTS: Clinical presentations and imaging
      findings in NS were varied. Cranial nerve abnormalities were the most common
      clinical presentation and involvement of the optic nerve in particular was
      associated with a poor prognosis for visual recovery. Isolated involvement of
      lower cranial nerves had a more favorable outcome. T(2) hyperintense parenchymal
      lesions were the most common imaging finding followed by meningeal enhancement.
      Long-term treatment consisted of prednisone and/or other immunomodulators
      (azathioprine, methotrexate or mycophenolate mofetil). CONCLUSION: Unlike
      systemic sarcoidosis, there is difficulty in making tissue diagnosis when
      involvement of CNS is suspected. MRI and CSF studies are sensitive in the
      detection of CNS inflammation but lack specificity, making the ascertainment of
      neurosarcoidosis a clinical challenge. In addition the low prevalence of the
      disease makes clinical trials difficult and therapeutic decisions are likely to
      be made from careful reporting from case studies.

PMID- 19383615
TI  - Risk factors for severe Dysphagia after concurrent chemoradiotherapy for head and
      neck cancers.
AB  - OBJECTIVE: The aim of this study was to investigate the risk factors for
      dysphagia induced by chemoradiotherapy for head and neck cancers. METHODS: Forty
      seven patients with head and neck cancers who underwent definitive
      chemoradiotherapy from December 1998 to March 2006 were reviewed retrospectively.
      Median age was 63 years (range, 16-81). The locations of the primary lesion were
      as follows: larynx in 18 patients, oropharynx in 11, nasopharynx in 7,
      hypopharynx in 7 and others in 4. Clinical stages were as follows: Stage II in 20
      and Stages III-IV in 27. Almost all patients underwent platinum-based concomitant
      chemoradiotherapy. The median cumulative dose of cisplatin was 100 mg/m(2)
      (range, 80-300) and median radiation dose was 70 Gy (range, 50-70). RESULTS:
      Severe dysphagia (Grade 3-4) was observed in 22 patients (47%) as an acute toxic
      event. One patient required tube feeding even at 12-month follow-up. In
      univariate analysis, clinical stage (III-IV) (P = 0.017), primary site (oro
      hypopharynx) (P = 0.041) and radiation portal size (>11 cm) (P < 0.001) were
      found to be associated with severe dysphagia. In multivariate analysis, only
      radiation portal size was found to have a significant relationship with severe
      dysphagia (P = 0.048). CONCLUSIONS: Larger radiation portal field was associated
      with severe dysphagia induced by chemoradiotherapy.

PMID- 19383612
TI  - Mass spectrometry-based protein profiling to determine the cause of lysosomal
      storage diseases of unknown etiology.
AB  - Diagnosis of lysosomal storage diseases (LSDs) can be problematic in atypical
      cases where clinical phenotype may overlap with other genetically distinct
      disorders. In addition, LSDs may result from mutations in genes not yet
      implicated in disease. Thus, there are individuals that are diagnosed with
      apparent LSD based upon clinical criteria where the gene defect remains elusive.
      The objective of this study was to determine whether comparative proteomics
      approaches could provide useful insights into such cases. Most LSDs arise from
      mutations in genes encoding lysosomal proteins that contain mannose 6-phosphate,
      a carbohydrate modification that acts as a signal for intracellular targeting to
      the lysosome. We purified mannose 6-phosphorylated proteins by affinity
      chromatography and estimated relative abundance of individual proteins in the
      mixture by spectral counting of peptides detected by tandem mass spectrometry.
      Our rationale was that proteins that are decreased or absent in patients compared
      with controls could represent candidates for the primary defect, directing
      biochemical or genetics studies. On a survey of brain autopsy specimens from 23
      patients with either confirmed or possible lysosomal disease, this approach
      identified or validated the genetic basis for disease in eight cases. These
      results indicate that this protein expression approach is useful for identifying
      defects in cases of undiagnosed lysosomal disease, and we demonstrated that it
      can be used with more accessible patient samples, e.g. cultured cells.
      Furthermore this approach was instrumental in the identification or validation of
      mutations in two lysosomal proteins, CLN5 and sulfamidase, in the adult form of
      neuronal ceroid lipofuscinosis.

PMID- 19383616
TI  - Welcome news in the Sentosa nurses case.

PMID- 19383617
TI  - Developing alliances: how advanced practice nurses became part of the
      prescription for Pennsylvania.
AB  - The authors describe how advanced practice nurses in Pennsylvania were able to
      successfully advocate for nursing-related legislative reforms through Governor
      Edward G. Rendell's signature health care reform plan (the "Prescription for
      Pennsylvania"). In addition to discussing advocacy efforts related to a series of
      nursing-related bills considered by the Pennsylvania Assembly in 2007, the
      article also describes years of hard work and foundational advocacy conducted by
      a broad coalition of nurses, which paved the way for the Prescription for
      Pennsylvania's reforms. By examining the successful tactics of Pennsylvania's
      nurse advocates, the authors conclude that policy makers' current interest in
      solving the health care crisis presents a tremendous opportunity for nurses to
      reform legislation. To seize this opportunity, nurses must learn to speak with a
      unified voice and build strong relationships with a broad range of bipartisan
      policy makers, funders, civic leaders, business leaders, and legislative
      advocates.

PMID- 19383618
TI  - The effect of patients' race on provider treatment choices in coronary care: a
      literature review for model development.
AB  - This selective literature review provides insight into the depth and breadth of
      the problem of unequal medical treatment of Blacks compared with Whites, with
      particular focus on coronary heart disease. Poor health outcomes among Blacks,
      when compared with Whites, are well documented, and these disparities are linked
      to lower quality of and less aggressive medical treatment. It is not clear why
      these disparities in treatment occur. This review provides theoretical frameworks
      that attempt to explain the effect of race on treatment and presents an analysis
      of the quality and strength of existing evidence of racial disparity related to
      coronary care. Based on the review, implications for policy makers and providers
      are identified.

PMID- 19383619
TI  - Expanding the knowledge base of resident and facility outcomes of care delivered
      by advanced practice nurses in long-term care: expert panel recommendations.
AB  - In 2003, a panel of nationally recognized experts in geriatric practice,
      education, research, public policy, and long-term care convened to examine and
      make recommendations about care quality and safety issues related to advanced
      practice nurses (APNs) in nursing home practice. This article reports on the
      panel recommendation that addressed expanding the evidence base of resident and
      facility outcomes of APN nursing home practice. A review of the small but
      important body of research related to nursing home APN practice suggests a
      positive impact on resident care and facility outcomes. Recommendations are made
      for critically needed research in four key areas: (a) APN nursing home practice,
      (b) relative value unit coding, (c) outcomes related to geropsychiatric and
      mental health nursing services, and (d) outcomes related to geriatric
      specialization. The APN role could be significantly enhanced and executed if its
      specific contribution to resident and facility outcomes was more clearly
      delineated through the recommended rigorous research.

PMID- 19383620
TI  - Patterns of community-based end-of-life care in rural areas of the United States.
AB  - There is relatively little empirical data on the supply of community-based end-of
      life (EOL) providers especially in rural areas despite projections for growth.
      This study examined the availability of community-based EOL providers in eight
      states using mapping techniques and statistical approaches. Analysis of variance
      and geographic information system approaches were used to compare the
      availability of community-based EOL providers at the county level by degree of
      rurality. Examining numbers of rural counties by provider, it was found that
      hospices were the least available community-based EOL providers in rural counties
      with 62% to 92% of rural counties not having hospice providers (exception:
      Vermont). When examining the number of providers by population older than 65
      years, few differences were found. It is concluded that there are substantially
      fewer hospice providers in the most rural areas, raising issues of access to
      care. Examination of both unadjusted and adjusted numbers of providers is
      important to understand community-based EOL provider supply.

PMID- 19383621
TI  - Delivery of nursing care in Alabama public schools.
AB  - Many states, including Alabama, allow registered nurses (RNs) in school settings
      to delegate procedures such as assistance with medication to unlicensed assistive
      personnel. In Alabama, the Board of Nursing(the Board) is accountable for
      enforcing the regulations that allow for this action. The Alabama Board of
      Nursing Administrative Code addresses delegation by school nurses and lists
      specific tasks that cannot be delegated because they require nursing judgment. As
      a result of this reporting requirement, Alabama's Center for Nursing, a division
      of the Board of Nursing, implemented an annual survey of school nurses to
      determine how nursing care is delivered to students in Alabama public schools.
      This study investigates the results of this survey and its implications for
      school nursing both in Alabama and in other states.

PMID- 19383623
TI  - An intronic single base exchange leads to a brown adipose tissue-specific loss of
      Ucp3 expression and an altered body mass trajectory.
AB  - Uncoupling protein 3 (Ucp3) is a transport protein of the inner mitochondrial
      membrane and presumably is implicated in the maintenance or tolerance of high
      lipid oxidation rates. Ucp3 is predominantly expressed in skeletal muscle and
      brown adipose tissue and is regulated by a transcription factor complex involving
      peroxisome proliferator-activated receptor-alpha, MyoD, and COUP transcription
      factor II. By analysis of a mutant Djungarian hamster model lacking Ucp3
      transcription specifically in brown adipose tissue, we identified a putative
      transcription factor-binding site that confers tissue specificity. A naturally
      occurring intronic point mutation disrupting this site leads to brown adipose
      tissue-specific loss of Ucp3 expression and an altered body weight trajectory.
      Our findings provide insight into tissue-specific Ucp3 regulation and, for the
      first time, unambiguously demonstrate that changes in Ucp3 expression can
      interfere with body weight regulation.

PMID- 19383622
TI  - Genetic locus on rat chromosome 20 regulates diet-induced adipocyte hypertrophy:
      a microarray gene expression study.
AB  - Obesity is a leading cause of diabetes mellitus and hypertension. Molecular
      signals produced by adipose tissue may contribute to the pathogenesis of these
      two disorders. We showed previously that a specific segment of rat chromosome 20
      (RNO20) contains a gene(s) regulating the degree of obesity, glucose intolerance,
      and hypertension in response to a chronic high-fat diet (HFD). Here we examined
      microarray gene expression profiles and cellular morphology of adipose tissues
      and whole body energy expenditure in this model. Adult male spontaneously
      hypertensive rats (SHR) and a congenic strain (SHR.1N) that differs from SHR by
      the above-mentioned segment of RNO20 were fed for 12 wk with HFD or a normal
      diet. At the end of this period, whole body energy expenditure was measured with
      indirect calorimetry. In response to HFD, body weight, fat pad weights, adipocyte
      size, and serum leptin levels increased significantly more in SHR.1N than SHR.
      Microarray gene expression profiles [Affymetrix, 15,923 genes and expressed
      sequence tags (ESTs)] showed that multiple genes of molecular pathways involved
      in lipogenesis were downregulated to a similar level in both strains, whereas
      genes involved in fatty acid oxidation and energy dissipation were upregulated
      less in SHR.1N than SHR. This was associated with lower whole body energy
      expenditure in SHR.1N than SHR at the end of the 12-wk HFD. Our results suggest
      that a gene(s) within the RNO20 segment regulate(s) HFD-induced increases in
      adiposity, and that this effect may be mediated, at least in part, by the impact
      of that gene(s) on fat burning and energy expenditure.

PMID- 19383624
TI  - Expression profiling of skeletal muscle in young bulls treated with steroidal
      growth promoters.
AB  - Dexamethasone (Dex), alone or in association with estrogens, is often illegally
      administered per os at very low dosage as a growth promoter in beef cattle, with
      effects that are opposite to the muscle wasting and atrophy induced by repeated
      administration at therapeutic dosages. In vitro and in vivo studies have
      investigated the catabolic effects of Dex at therapeutic doses on skeletal
      muscle, demonstrating an increase in the expression of GDF8 (myostatin) gene, a
      well-known negative regulator of skeletal muscle mass, in a dose-dependent way.
      This suggested a direct role of myostatin in Dex-induced muscle wasting. In the
      present study, an oligonucleotide microarray platform was used to compare
      expression profiles of beef cattle muscle in animals treated with either Dex or
      Dex plus 17-beta estradiol (Estr) administered at subtherapeutic dosage, against
      untreated controls. Data analysis demonstrates that the expression profiles were
      strongly affected by Dex treatment with hundreds of genes upregulated with
      relevant fold-change, whereas seven genes were downregulated including the
      myostatin gene. On the contrary, the number of differentially regulated genes was
      lower in response to the addition of Estr to the Dex treatment. Differentially
      regulated genes were analyzed to describe the effects of these treatments on
      muscle physiology, highlighting the importance of specific pathways (e.g., Wnt or
      cytokine signaling) and cellular processes (e.g., cell shape and motility).
      Finally, the observed differences in the expression profile will allow the
      development of indirect bio-markers to detect illegal Dex treatments in beef
      cattle using quantitative RT-PCR.

PMID- 19383625
TI  - BTLA targeting modulates lymphocyte phenotype, function, and numbers and
      attenuates disease in nonobese diabetic mice.
AB  - The novel coinhibitory receptor BTLA may have a regulatory role in maintaining
      peripheral tolerance; however, its role in autoimmune diabetes is unknown. In
      this study, we show that anti-BTLA mAb 6F7 selectively depleted pathogenic B and
      CD4+ T(H) cells; enhanced the proportion of cells with the forkhead box p3+ PD
      1+CD4+ regulatory T phenotype; and increased the production of potentially
      protective (IL-10) and detrimental (IL-2, IFN-gamma) cytokines in NOD mice. As
      interactions between BTLA and PD-1 coinhibitory pathways have been described in
      the cardiac allograft model, we also investigated if these pathways may have
      significant interaction in autoimmune diabetes. Anti-BTLA inhibited anti-PD-1
      potentiated total IL-12 (p40+p70) production, suggesting the possibility that
      anti-BTLA may have a greater effect in the setting of anti-PD-1-triggered
      diabetes. To test this, NOD mice at 4 and 10 weeks of age were treated with anti
      BTLA mAb, anti-PD-1 mAb, both mAb, or isotype control and were monitored for
      diabetes development. Although anti-BTLA mAb delayed diabetes onset significantly
      in 10- but not 4-week-old NOD mice, anti-BTLA mAb attenuated anti-PD-1-induced
      diabetes in both age groups. Hence, strategies targeting BTLA+ lymphocytes or
      therapies enhancing the BTLA-negative cosignal may prove valuable in treating
      autoimmune diabetes.

PMID- 19383627
TI  - The impact of federal bioterrorism funding programs on local health department
      preparedness activities.
AB  - Using the 2005 National Association of County and City Health Officers Profile of
      Local Health Departments data set, bivariate probit and Heckman selection models
      were used to test the hypothesis that the level of federal funding received for
      bioterrorism preparedness is related to the preparedness activities undertaken by
      local health departments. Overall budget, leadership, and crisis experience are
      found to be the most important determinants of local preparedness activity, but
      Centers for Disease Control and Prevention preparedness funding plays a mediating
      role by building capacity through the hiring of one key leadership position, the
      emergency preparedness coordinator. Additional research is needed to determine
      the potential impact of these funds on other aspects of the local public health
      system, such as the scope of services delivered, to determine secondary effects
      of the program.

PMID- 19383626
TI  - Impaired M. tuberculosis-mediated apoptosis in alveolar macrophages from HIV+
      persons: potential role of IL-10 and BCL-3.
AB  - The mechanism of increased MTb disease susceptibility in HIV+ persons remains
      poorly understood. Apoptosis of macrophages in response to MTb represents a
      critical host defense response, and decreased apoptosis may represent a mechanism
      of increased susceptibility to MTb in HIV. In the current study, MTb-mediated
      apoptosis of human AM was reduced in HIV+ subjects compared with healthy subjects
      in a TNF-alpha-dependent manner. IL-10 levels in BALF from HIV+ persons were
      significantly elevated compared with HIV- persons, and exogenous IL-10 reduced
      MTb-mediated apoptosis in healthy AM, suggesting that IL-10 could mediate
      decreased apoptosis observed in HIV. Further study showed that IL-10 reduced TNF
      release in response to MTb in AM through a reduction in TNF mRNA levels, and
      exogenous TNF could partially reverse IL-10-associated effects on AM apoptosis.
      IL-10 did not influence p-IRAK, IkappaB degradation, or NF-kappaB p65 nuclear
      translocation in response to MTb, but IL-10 did increase levels of AM BCL-3, an
      inhibitor of NF-kappaB nuclear activity. BCL-3 knockdown in human macrophages
      increased MTb-mediated TNF release. Importantly, BCL-3 levels in AM from HIV+
      subjects were higher compared with healthy subjects. Taken together, these data
      suggest that elevated lung levels of IL-10 may impair MTb-mediated AM apoptosis
      in HIV through a BCL-3-dependent mechanism. BCL-3 may represent a potential
      therapeutic target to treat or prevent MTb disease in HIV+ persons.

PMID- 19383628
TI  - Intimate partner violence among Asian immigrant communities: health/mental health
      consequences, help-seeking behaviors, and service utilization.
AB  - Intimate partner violence (IPV) is a serious epidemic among Asian immigrant
      communities. Yet little is known about the scope, nature, and related contextual,
      cultural, and social factors of IPV among this population. In particular, the
      lack of research has been evident in examining health and mental health outcomes
      of IPV and service utilization, revealing notable gaps in health disparities
      which result in a failure to provide relevant services and law enforcement
      protection for battered Asian immigrant women. This article examines critically
      the growing body of literature on IPV among Asian immigrant populations in
      several areas: (a) the context of IPV: cultural, social, and individual/familial,
      (b) prevalence of IPV, (c) physical health and increased risk for sexually
      transmitted disease and HIV/AIDS, (d) mental health consequences and substance
      use, (e) social support and help-seeking behaviors, and (f) barriers to service
      utilization. Future directions for practice, policy, and research are discussed.

PMID- 19383629
TI  - Toward a multi-level, ecological approach to the primary prevention of sexual
      assault: prevention in peer and community contexts.
AB  - Although sexual assault prevention programs have been increasingly successful at
      improving knowledge about sexual violence and decreasing rape-supportive
      attitudes and beliefs among participants, reducing sexually assaultive conduct
      itself remains an elusive outcome. This review considers efforts to support
      change for individuals by creating prevention strategies that target peer network
      and community-level factors that support sexual violence. To this end, the
      article examines successful ecological prevention models from other prevention
      fields, identifies the components of multilevel prevention that appear critical
      to efficacy and discusses their application to existing and emerging sexual
      violence prevention strategies.

PMID- 19383630
TI  - Factors influencing attitudes to violence against women.
AB  - Attitudes toward men's violence against women shape both the perpetration of
      violence against women and responses to this violence by the victim and others
      around her. For these reasons, attitudes are the target of violence-prevention
      campaigns. To improve understanding of the determinants of violence against women
      and to aid the development of violence-prevention efforts, this article reviews
      the factors that shape attitudes toward violence against women. It offers a
      framework with which to comprehend the complex array of influences on attitudes
      toward violent behavior perpetrated by men against women. Two clusters of
      factors, associated with gender and culture, have an influence at multiple levels
      of the social order on attitudes regarding violence. Further factors operate at
      individual, organizational, communal, or societal levels in particular, although
      their influence may overlap across multiple levels. This article concludes with
      recommendations regarding efforts to improve attitudes toward violence against
      women.

PMID- 19383631
TI  - Characterization of six human disease-associated inversion polymorphisms.
AB  - The human genome is a highly dynamic structure that shows a wide range of genetic
      polymorphic variation. Unlike other types of structural variation, little is
      known about inversion variants within normal individuals because such events are
      typically balanced and are difficult to detect and analyze by standard molecular
      approaches. Using sequence-based, cytogenetic and genotyping approaches, we
      characterized six large inversion polymorphisms that map to regions associated
      with genomic disorders with complex segmental duplications mapping at the
      breakpoints. We developed a metaphase FISH-based assay to genotype inversions and
      analyzed the chromosomes of 27 individuals from three HapMap populations. In this
      subset, we find that these inversions are less frequent or absent in Asians when
      compared with European and Yoruban populations. Analyzing multiple individuals
      from outgroup species of great apes, we show that most of these large inversion
      polymorphisms are specific to the human lineage with two exceptions, 17q21.31 and
      8p23 inversions, which are found to be similarly polymorphic in other great ape
      species and where the inverted allele represents the ancestral state.
      Investigating linkage disequilibrium relationships with genotyped SNPs, we
      provide evidence that most of these inversions appear to have arisen on at least
      two different haplotype backgrounds. In these cases, discovery and genotyping
      methods based on SNPs may be confounded and molecular cytogenetics remains the
      only method to genotype these inversions.

PMID- 19383633
TI  - Volume of foremilk, hindmilk, and total milk produced by mothers of very preterm
      infants born at less than 28 weeks of gestation.
AB  - The purpose of this study is to describe foremilk volume (milk produced in the
      first 3 minutes of pumping), hindmilk volume (remainder of milk produced), and
      total milk volume produced by mothers of very preterm infants at 3 weeks
      postpartum and associated factors. Mothers (n = 24) mechanically pump their
      breasts a median (minimum, maximum) of 7 times (5, 9 times) per 24 hours for a
      total of 15 minutes (9.4, 23.9 minutes) each time. Foremilk, hindmilk, and total
      milk volumes are 183 mL per 24 hours (80, 810), 318 mL per 24 hours (98, 1007),
      and 545 mL per 24 hours (224, 1817), respectively. Milk volumes are not
      associated with mother's age, race or ethnic background, education, parity,
      reported prepregnancy body mass index, previous breastfeeding experience,
      frequency of milk pumping, longest time between pumps, infant birth weight, or
      multiple births. The degree of pre-maturity (<26 weeks vs 26(0/7)-27(6/7) weeks)
      is significantly related to the relative proportion of foremilk/hindmilk volumes
      (45:55 vs 36:65, respectively).

PMID- 19383632
TI  - Formin1 disruption confers oligodactylism and alters Bmp signaling.
AB  - Proper limb development requires concerted communication between cells within the
      developing limb bud. Several molecules have been identified which contribute to
      the formation of a circuitry loop consisting in large part of secreted proteins.
      The intracellular actin nucleator, Formin 1 (Fmn1), has previously been
      implicated in limb development, but questions remain after the identification of
      a Gremlin transcriptional enhancer within the 3' end of the Fmn 1 locus. To
      resolve this issue, a knockout mouse devoid of Fmn1 protein was created and
      characterized. The mice exhibit a reduction of digit number to four, a deformed
      posterior metatarsal, phalangeal soft tissue fusion as well as the absence of a
      fibula to 100% penetrance in the FVB genetic background. Importantly, this mutant
      allele does not genetically disrupt the characterized Gremlin enhancer, and
      indeed Gremlin RNA expression is upregulated at the 35 somite stage of
      development. Our data reveal increased Bone Morphogenetic Protein (Bmp) activity
      in mice which carry a disruption in Fmn1, as evidenced by upregulation of Msx1
      and a decrease in Fgf4 within the apical ectodermal ridge. Additionally, these
      studies show enhanced activity downstream of the Bmp receptor in cells where Fmn1
      is perturbed, suggesting a role for Fmn1 in repression of Bmp signaling.

PMID- 19383634
TI  - People's initiative to counteract misinformation and marketing practices: the
      Pembo, Philippines, breastfeeding experience, 2006.
AB  - The Philippines is among 42 countries accounting for 90% of under 5-year-old
      deaths. Only 16% of 4 to 5 month old Filipinos exclusively breastfeed. In 2006,
      almost $100 million was spent advertising formula in the Philippines. To counter
      widespread misinformation and improve breastfeeding a peer counseling
      intervention was developed to target mothers with infants less than 2 months of
      age who were not exclusively breastfeeding or had difficulty breastfeeding.
      Participants received 3 peer counseling visits. At baseline and 3 weeks later, 24
      hour food recalls for infants were collected. The number of exclusively formula
      fed infants decreased seven-fold (P < .001). Mixed-fed infants decreased 37% (P <
      .001). Overall, of the 148 nonexclusively breastfeeding infants, 69.5% had
      changed feeding methods after 3 home visits, 76% of whom to exclusive
      breastfeeding. Community-based peer counseling was associated with a drastic
      improvement of exclusive breastfeeding practices. This intervention evolved and
      became sustainable by engaging political figures, cities, and communities
      throughout the process. In 2 years, the Department of Health, World Health
      Organization (WHO) program has scaled up to improve health service delivery for
      161,612 persons in depressed urban communities in the Philippines.

PMID- 19383636
TI  - Effect of melatonin in the prevention of postoperative pericardial adhesion
      formation.
AB  - To evaluate the efficacy of melatonin in preventing postoperative pericardial
      adhesions, 12 single breed dogs were randomized equally into experimental
      (melatonin) and control groups. After ketamine anesthesia, a vertical midsternal
      incision was done and the parietal pericardium of the inferior site of the heart
      was opened vertically. To promote adhesion formation, abrasions were created on
      both parietal and visceral pericardial surfaces in an area of 2 cm2 with two
      vertically reciprocal movements of dry gauze. In the melatonin group, 5% ethanol
      plus 10 mg/kg melatonin in 10 ml NaCl and, in control group, 10 ml NaCl dilution
      vehicle containing 5% ethanol was instilled intra-pericardium on to the abrasion
      sites. After a 6-week recovery period, the animals were evaluated for grading of
      adhesion formation by an examiner blinded to the groups. The extent of adhesions
      was graded from 0 (no adhesion) to 3 (total involvement of the traumatized area).
      The results showed that adhesion scores were significantly lower in melatonin
      group (1.00+/-0.63) compared with controls (2.66+/-0.51); P=0.001. We conclude
      that melatonin administration effectively reduced postoperative pericardial
      adhesions in dogs. The use of melatonin in the prevention of pericardial adhesion
      formation in human subjects warrants further investigations.

PMID- 19383635
TI  - Neuropathogenesis and neurovirulence of live flaviviral vaccines in monkeys.

PMID- 19383637
TI  - Safety and efficacy of transbrachial intra-aortic balloon pumping with the use of
      7-Fr catheters in patients undergoing coronary bypass surgery.
AB  - We report the cases of five consecutive patients undergoing coronary artery
      bypass grafting (CABG) who required a transbrachial approach for 7-Fr catheter
      intra-aortic balloon pumping (IABP) insertion because of unsuitable femoral
      arteries. No adverse outcomes occurred in any patient during a mean 72 h of IABP
      support. Our experience with 7-Fr catheters appears to confirm previous reports
      of the safety and efficacy of transbrachial IABP assistance and suggests that
      such support can be provided safely for an extended duration with the use of
      these smaller catheters.

PMID- 19383638
TI  - Transpulmonary versus continuous thermodilution cardiac output after valvular and
      coronary artery surgery.
AB  - Residual left-sided valvular insufficiencies after valvular surgery may confound
      transpulmonary thermodilution cardiac output (COtp). We compared the technique
      with the continuous right-sided thermodilution technique (CCO) after valvular
      surgery (n=8) and coronary artery surgery (n=8). Patients with pulmonary and
      femoral artery catheters in the intensive care unit (ICU) were included. After
      valvular surgery, there was minimal aortic insufficiency in four patients and
      minimal to moderate mitral valve insufficiency in six. Five fluid loading steps
      (250 ml) were done in each patient. CCO and COtp were measured prior to and 15
      min after each step. The cardiac output was lower after valvular than coronary
      artery surgery but responses to fluid loading steps were similar among surgery
      types and techniques. After valvular and coronary artery surgery, cardiac output
      was lower prior to responses than in non-responses to fluids, by either
      technique. After valvular surgery, COtp and CCO correlated (r=0.64, P<0.001,
      n=48) but fluid-induced changes did not. After coronary artery surgery, COtp and
      CCO correlated (r=0.81, P<0.001) and changes also did (r=0.55, P<0.001). At fluid
      induced CCO increases <20%, the r for changes in cardiac output measured by both
      techniques was similar after valvular and coronary artery surgery. Thus, COtp and
      CCO were of similar value in predicting and monitoring fluid responses after both
      surgery types. This argues against left-sided valvular insufficiencies
      confounding COtp.

PMID- 19383639
TI  - On-pump beating heart mitral valve repair in patients with patent bypass grafts
      and severe ischemic cardiomyopathy.
AB  - Re-operative mitral valve surgery in patients with poor ventricular function can
      be challenging especially in the presence of patent bypass grafts. We report the
      case of 11 patients with severe ischemic cardiomyopathy who underwent reoperative
      mitral valve repair through a limited right thoracotomy approach, on a non
      fibrillating beating heart. All patients had their valves successfully repaired
      with no operative mortality and minimal morbidity. The technical aspects of the
      procedure are discussed, and the pertinent literature reviewed.

PMID- 19383640
TI  - Will Americans support the individual mandate?
AB  - An individual mandate is an important feature of many recent plans to achieve
      universal health insurance coverage in the United States, without radically
      changing the way most Americans get health care and coverage. Using national
      public opinion data, we find that on its own, an individual mandate does not have
      broad support across partisan and sociodemographic groups. Policymakers who
      choose to pursue an individual mandate for policy reasons may expand the base of
      supporters by incorporating it into a "shared-responsibility" plan that includes
      requirements for employers, government, and insurers.

PMID- 19383641
TI  - Feasibility and reproducibility of left ventricular rotation parameters measured
      by speckle tracking echocardiography.
AB  - AIMS: This study sought to find the most robust method for left ventricular (LV)
      rotation measurement by speckle tracking echocardiography (STE) with the new QLAB
      Advanced Quantification Software (version 6.0, Philips, Best, The Netherlands).
      METHODS AND RESULTS: The study population consisted of 40 non-selected patients
      (mean age 48 +/- 18 year, 20 men) and 50 non-selected healthy volunteers (mean
      age 34 +/- 12 year, 21 men). Feasibility and intra-observer reproducibility of
      the measurement of LV rotation parameters by STE were assessed for two different
      methods (Method A: six tracking points placed mid-myocardial and Method B: six
      tracking points placed endocardial and epicardial forming six myocardial
      segments). Subsequently, inter-observer and temporal reproducibility of the most
      robust method were assessed. Complete LV rotation assessment was more feasible
      with Method A (60 out of 90 subjects, 67% vs. 50 out of 90 subjects, 56%). In the
      49 subjects in whom both Methods A and B were feasible, intra-observer
      reproducibility of LV rotation parameters was better with Method A (variabilities
      2 +/- 3 to 10 +/- 9% vs. 2 +/- 4 to 21 +/- 18%). With this method, inter-observer
      variability varied from 4 +/- 4 to 13 +/- 9% and temporal variability from 4 +/-
      6 to 19 +/- 15%. CONCLUSION: The most robust method to assess LV rotation with
      QLAB software is from the mid-myocardium. This method is feasible in
      approximately two-thirds of subjects and has good intra-observer, inter-observer,
      and temporal reproducibility, allowing to study changes over time in LV rotation
      in an individual patient.

PMID- 19383642
TI  - Uncommon acquired Gerbode defect (left ventricular to right atrial communication)
      following a tricuspid annuloplasty without concomitant mitral surgery.
AB  - Left ventricular (LV) to right atrial (RA) communication, also known as Gerbode
      defect, is very rare, usually congenital but sometimes also acquired. Cases of
      Gerbode defect have been reported after left valve surgery, usually valve
      replacement. We describe the first case of LV-RA communication following a
      tricuspid annuloplasty not combined to a left valve surgery. The case we report
      concerns a 73-year-old woman who underwent a double-valve surgery (pulmonary
      valve replacement and tricuspid annuloplasty) for symptomatic severe right heart
      failure due to post-endocarditis pulmonary valve regurgitation. A LV-RA shunt was
      discovered 1 year after surgery. This case report confirms the responsibility of
      a tricuspid annuloplasty in an acquired LV-RA shunt.

PMID- 19383643
TI  - Regulation of matrix metalloproteinases and their inhibitors by interferon-beta:
      a longitudinal study in multiple sclerosis patients.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) represent a large family of
      proteolytic enzymes, with some members being implicated in the immunopathogenesis
      of multiple sclerosis (MS). Interferon (IFN)-beta is one of the current mainstays
      in MS therapy and known to downregulate the expression of MMP-9. However, only
      sparse information is available on the effects of IFN-beta on the other 20
      members of the MMP family. METHODS: This is a longitudinal analysis on the RNA
      expression pattern of all known MMPs and their endogenous inhibitors before and
      after 1 and 6 months of IFN-beta therapy. RNA expression levels were assessed in
      peripheral venous blood cells from 14 MS patients and 8 matched controls by real
      time-PCR. RESULTS: RNA expression levels before treatment differed in part in MS
      patients compared to healthy controls (MMP-9, MMP-14, MMP-19, TIMP-1, TIMP-2).
      Some of the MMPs responded to therapy specifically (MMP-8, MMP-9, MMP-19),
      whereas others remained unchanged over time. CONCLUSIONS: These data suggest that
      MMPs may differ in their expression levels in MS patients and that this group of
      enzymes is differentially regulated during the treatment with IFN-beta in MS for
      at least 6 months.

PMID- 19383644
TI  - Vitamin D status and effect of low-dose cholecalciferol and high-dose
      ergocalciferol supplementation in multiple sclerosis.
AB  - BACKGROUND: Vitamin D is important for bone health and immune regulation, and has
      been shown to be low in multiple sclerosis (MS). We sought to determine the
      effect of over the counter low dose cholecalciferol (LDC) and high dose
      ergocalciferol (HDE) on the vitamin D levels in MS patients. METHODS: We
      retrospectively evaluated serum 25-hydroxy-vitamin D [25(OH)D] levels of 199
      patients (CIS, n = 32; RRMS, n = 115; PPMS, n = 10; SPMS, n = 16; Transverse
      Myelitis (TM), n = 9; other neurological diseases, n = 16) attending our clinic
      between 2004 and 2008. We examined the change in 25(OH)D levels in 40 MS patients
      who took either LDC (< or =800 IU/day) or HDE (50,000 IU/day for 7-10 days,
      followed by 50,000 IU weekly or biweekly). RESULTS: The average 25(OH)D level was
      71 +/- 39 nmol/L (Mean +/- SD), and 167(84%) patients had insufficient levels (<
      or =100 nmol/L) of 25(OH)D. The patients supplemented with LDC did not have a
      significant increase in their 25(OH)D levels. However, 25(OH)D levels increased
      by 42 nmol/L (P = 0.01) in the patients originally taking LDC and then prescribed
      HDE. Optimal levels (> or =100 nmol/L) were only achieved in less than 40% of
      patients. CONCLUSIONS: We conclude that large numbers of patients with MS and TM
      in our cohort are deficient in vitamin D. HDE significantly elevated 25(OH)D
      levels in MS patients and was more effective at increasing 25(OH)D levels than
      LDC. Prospective studies are required to determine appropriate dosing regimen to
      achieve optimal levels in the majority of MS patients and to ascertain the
      safety, immunological response, and ultimately the clinical efficacy of vitamin D
      replacement therapy.

PMID- 19383645
TI  - The long-term cost of multiple sclerosis in France and potential changes with
      disease-modifying interventions.
AB  - OBJECTIVE: To evaluate the long-term costs and quality of life (QoL) with and
      without disease-modifying treatments (DMTs) of patients with multiple sclerosis
      (MS). METHODS: Data on resource consumption, productivity losses, QoL (utility),
      and fatigue were collected from 1355 patients registered with a patient
      association and descriptive analyses was performed.A Markov model was developed
      to estimate costs and utility over 20 years using the survey data. Disease
      progression without DMTs was taken from an epidemiological cohort in France
      (EDMUS cohort, LYON). Progression under DMTs was estimated from the Stockholm MS
      registry. Results are presented as cost per quality-adjusted life-years (QALYs),
      from the societal perspective, in EUR2007, discounted at 3%. RESULTS: Mean
      Expanded Disability Status Scale (EDSS) was 4.4 and mean total annual costs per
      patient were EUR44,400, of which 47% were productivity losses and 11% informal
      care. Public payers cover an estimated 48% of costs. Mean utility was 0.52, and
      the loss compared with the normal population was estimated at 0.28. Costs and
      utility ranged from EUR16,000 and 0.79 at EDSS 1 to EUR76,000 and 0.11 at EDSS 8
      9.Over 20 years, costs were estimated at EUR429,000 and QALYs at 8.96 for
      patients without DMTs and at EUR433,207 and 9.24 QALYs if all patients were
      starting treated with DMTs at EDSS 1-3. CONCLUSION: Although the data for this
      analysis come from different sources, the results indicate that the cost increase
      with DMTs is moderate.

PMID- 19383646
TI  - The search for responsive clinical endpoints in primary progressive multiple
      sclerosis.
AB  - OBJECTIVE: To determine whether in primary progressive multiple sclerosis (PPMS)
      combining scores of Expanded Disability Status Scale (EDSS) with data from Timed
      25-Foot Walk (T25FW) and 9-Hole Peg Test (9HPT) would produce a clinical endpoint
      that has a higher event rate than EDSS alone. METHODS: In a group of 161 PPMS
      patients, EDSS, T25FW, and 9HPT were performed at three time points over 2 years.
      We calculated how many patients showed clinically meaningful deterioration (or
      improvement) on individual and combined scales. We defined improvements on one
      scale with deterioration on the other as "opposing changes." We investigated the
      possible effect of baseline disability on the definition of our endpoint by
      dividing the population into two subsets of patients determined by baseline EDSS
      level. RESULTS: On individual scales, event rates were highest on T25FW: 34% and
      46% 1 year and 2 years after baseline. On a combination of two scales, at 1 year
      the event rate was highest on T25FW/9HPT (46%; with a high rate of opposing
      changes) and at 2 years on T25FW/EDSS (57%; with a lower rate of opposing
      changes). In both subsets, event rates were highest on T25FW and (at 2 years) on
      the combination of T25FW/EDSS. CONCLUSIONS: T25FW has the highest event rate as a
      single scale, independent of baseline disability level. A term of 2 years turned
      out to be more meaningful to observe than 1 year. "Worsening on either T25FW or
      EDSS" is the most appropriate composite endpoint in this patient group.

PMID- 19383648
TI  - How should psychology interventions be reported?
AB  - Psychology requires new heuristics for intervention research and reporting. There
      are problems with evidence-based practice (EBP) and with publications reporting
      intervention studies in Psychology. These issues are connected. EBP is associated
      with unsustainable levels of Waste, Inertia, Invalidity, Simplisticity and
      Opacity. Eleven domains of behaviour change are defined which encompass a vast
      array of programmes, interventions and techniques. These procedures are delivered
      in a multitude of combinations enabling millions of different interventions in
      Psychology. Reporting an intervention study in Psychology is a complex operation.
      A taxonomy for intervention reports is described.

PMID- 19383647
TI  - Past environmental sun exposure and risk of multiple sclerosis: a role for the
      Cdx-2 Vitamin D receptor variant in this interaction.
AB  - Multiple studies have provided evidence for an association between reduced sun
      exposure and increased risk of multiple sclerosis (MS), an association likely to
      be mediated, at least in part, by the vitamin D hormonal pathway. Herein, we
      examine whether the vitamin D receptor (VDR), an integral component of this
      pathway, influences MS risk in a population-based sample where winter sun
      exposure in early childhood has been found to be an important determinant of MS
      risk. Three polymorphisms within the VDR gene were genotyped in 136 MS cases and
      235 controls, and associations with MS and past sun exposure were examined by
      logistic regression. No significant univariate associations between the
      polymorphisms, rs11574010 (Cdx-2A > G), rs10735810 (Fok1T > C), or rs731236
      (Taq1C > T) and MS risk were observed. However, a significant interaction was
      observed between winter sun exposure during childhood, genotype at rs11574010,
      and MS risk (P = 0.012), with the 'G' allele conferring an increased risk of MS
      in the low sun exposure group (</=2 h/day). No significant interactions were
      observed for either rs10735810 or rs731236, after stratification by sun exposure.
      These data provide support for the involvement of the VDR gene in determining MS
      risk, an interaction likely to be dependent on past sun exposure.

PMID- 19383649
TI  - A review of music-based intervention reporting in pediatrics.
AB  - Determining how music-based interventions have been described in published
      literature is an important first step in evaluating whether guidelines for
      reporting music-based interventions need to be developed. Twenty-two pediatric
      intervention studies that met specified inclusion criteria were reviewed for
      content in 11 areas. This review revealed significant gaps in intervention
      reporting. Problems were particularly pronounced in eight areas: music qualities,
      intervention materials, intervention components, intervention delivery schedule,
      interventionist, treatment fidelity, setting and music delivery method.
      Development of reporting guidelines for music-based interventions is needed to
      improve reporting and advance evidence-based practice.

PMID- 19383651
TI  - Health and happiness among older adults: a community-based study.
AB  - The relationship between health and happiness was explored using a cross
      sectional survey of 383 community-dwelling older adults. As a function of self
      reported health, median happiness was increasing at a decreasing rate; happiness
      variability was decreasing at a decreasing rate. In multivariable logistic
      regression, lowest-quartile happiness was associated with poverty, unfavorable
      subjective health, debilitating pain and urinary incontinence, but not with the
      comorbidity count or other comorbidities. The results, robust to common method
      bias, suggest that subjective health measures are better predictors of happiness
      than objective measures are, except for conditions that disrupt daily functioning
      or are associated with social stigma.

PMID- 19383652
TI  - Perfectionism and the five-factor personality traits as predictors of mortality
      in older adults.
AB  - The major hypothesis of the study was that perfectionism as a personality trait,
      along with the five-factor personality traits and dispositional optimism, is
      strongly associated with mortality in late life. After baseline assessment of
      health and personality traits as predictors of mortality, 450 participants were
      followed over a period of 6.5 years. Consistent with our hypotheses, findings
      demonstrated that risk of death was significantly greater for high scorers in
      perfectionism and neuroticism, compared to low scorers at the time of base line.
      Conversely, risk of death was significantly lower for high scorers in
      conscientiousness, extraversion and optimism. Implications for health and
      longevity are discussed.

PMID- 19383653
TI  - Development and validation of measures of religious involvement and the cancer
      experience among African Americans.
AB  - Research indicates that African Americans diagnosed with cancer tend to use
      religion in coping. However less is known about the specific role that religion
      plays in the coping process. Based on previous qualitative work, five instruments
      were developed to assess the role of religious involvement in cancer coping: God
      as helper, God as healer, Faith in healing, Control over cancer and New
      perspective. The instruments were administered to 100 African Americans with
      cancer. Each exhibited high internal reliability, and concurrent and discriminant
      validity. These instruments may have applied value for the development of church
      based cancer support/survivorship interventions.

PMID- 19383654
TI  - Why my classmates drink: drinking motives of classroom peers as predictors of
      individual drinking motives and alcohol use in adolescence -- a mediational
      model.
AB  - A structural equation model was estimated based on a Swiss national sample of
      5649 12- to 18-year-olds to test whether individual drinking motives mediate the
      link between classmates' motives and individual alcohol use. Results showed that
      the social, enhancement, coping and conformity motives of individual students are
      associated with the corresponding motive dimension of other students in the
      class. No direct effect of the four classmates' motives on individual drinking,
      but an indirect effect via individual motives was observed. It appears that
      drinking motives within the adolescent social environment exert their influence
      on drinking by way of shaping individual motives.

PMID- 19383655
TI  - College smokers' estimates of their probabilities of remaining a smoker in the
      near future.
AB  - Community college and university smokers (N = 662) estimated their probability
      (0% to 100%) of remaining a smoker one and six months later and reported their
      confidence in their estimates. Smoking status was assessed at each time point.
      Analyses controlled for several correlates of both smoking status and probability
      estimates of remaining a smoker. Estimates of smoking status interacted with
      confidence to predict smoking status at one month, but only estimates predicted
      smoking status at six months. Findings suggest that: 1) personal estimate of
      future smoking status is a unique correlate of continued smoking; and 2)
      confidence in personal estimates is a strong moderator for short-term projections
      of smoking status.

PMID- 19383656
TI  - Stereotype threat and the exercise/dietary health intentions of overweight women.
AB  - Overweight individuals face significant prejudice and discrimination in daily
      life yet it is not well understood how factors associated with prejudice and
      discrimination (i.e. negative social stereotypes) impact overweight individuals'
      exercise/dietary health intentions. It is proposed that the Model of Stereotype
      Threat may serve as a useful theoretical tool for interpreting the situational
      impact of negative stereotypes on the health intentions of overweight
      individuals. Analyses with a community sample of 100 clinically overweight women
      showed that priming overweight women to think about weight-related stereotypes
      led to significantly diminished exercise and dietary health intentions.

PMID- 19383657
TI  - Self-rated health and allostatic load in women working in two occupational
      sectors.
AB  - This study set out to investigate how biological dysregulation, in terms of
      allostatic load (AL), relates to self-rated health (SRH) in women. Data on SRH
      and 12 biomarkers used to assess AL were available for 241 employees from the
      health care sector and 98 employees from the IT/media sector. In line with the
      hypothesis, results showed that a poor SRH, along with occupational sector, age
      and education, were significantly associated with a high AL, particularly for
      those working within the health care sector. This association between a poor SRH
      and AL, suggests a link between SRH and biological dysregulation.

PMID- 19383658
TI  - Autonomous regulation and locus of control as predictors of antiretroviral
      medication adherence.
AB  - The purpose of the current study was to examine the interrelationships between
      autonomous regulation (AR) and locus of control (LOC) and their prediction of
      Antiretroviral Therapy (ART) adherence among 189 HIV+ patients. Path analyses
      revealed that neither AR nor LOC directly predicted adherence although AR was
      indirectly related when mediated by self-efficacy. AR was positively related to
      internal and doctors LOC, but not related to chance or others LOC. Overall,
      results support Self-determination Theory's conceptualization of AR and indicate
      that AR may be a more robust predictor of medication adherence than LOC
      variables.

PMID- 19383659
TI  - Early childhood psychological problems predict a poor sense of coherence in
      adolescents: a 15-year follow-up study.
AB  - The aim of the present 15-year follow-up was to study the association between
      childhood psychological symptoms and sense of coherence (SOC) in adolescence.
      Destructive behaviour at three years, attention problems and thought problems at
      12 years, attention problems, anxiety/depression, delinquency and somatic
      complaints at 15 years predicted a poor SOC at 18 years. Problems reported by
      adolescents themselves explained a poor SOC much more often than problems
      reported by parents. The identification of early childhood behavioural problems
      helps us to identify children at risk of ill-being in adolescence since problems
      seem to persist unchanged until that period of life.

PMID- 19383660
TI  - Providing sex education to persons with learning disabilities in the era of
      HIV/AIDS: tensions between discourses of human rights and restriction.
AB  - Research suggests that disabled people may be at increased risk for HIV
      infection, yet are excluded from HIV prevention campaigns. Historically people
      with learning disabilities have been constructed as either being asexual or
      sexually uninhibited, and sex education considered to be unnecessary or
      potentially harmful. This article reports on findings of a qualitative study
      exploring the challenges expressed by participants who provide sex education for
      persons with learning disabilities, revealing a tension between a human rights
      discourse and a discourse of restriction of sexual behaviours. Sex education, in
      the context of HIV/AIDS, may potentially construct sex as dangerous, echoing past
      constructions of disabled people's sexuality as problematic.

PMID- 19383661
TI  - The PedsQL 4.0 Generic Core Scales Young Adult Version: feasibility, reliability
      and validity in a university student population.
AB  - This study determined the feasibility, reliability and validity of the 23-item
      PedsQL 4.0 Generic Core Scales Young Adult Version as a multidimensional measure
      of health-related quality of life. The study population consisted of 1273
      students ages 18-25. The PedsQL (Physical, Emotional, Social, Work/School
      Functioning) Young Adult Version and SF-8 were self-administered. The PedsQL
      evidenced minimal missing responses, achieved excellent reliability for the Total
      Scale Score, acceptable reliability for subscale scores, distinguished between
      healthy young adults and young adults with chronic health conditions and was
      significantly correlated with the SF-8. The results demonstrate the measurement
      properties of the PedsQL Young Adult Version.

PMID- 19383662
TI  - Issues for DSM-V: I) including biological variables to objectively comfort the
      clinical diagnosis of borderline personality disorder and II) proposing a new
      subcategory to be included in the criteria sets for further study.

PMID- 19383663
TI  - Co-morbid social phobia in schizophrenia.
AB  - BACKGROUND: The co-morbid occurrence of anxiety disorders and schizophrenia has
      recently begun to be investigated. Social anxiety may be especially important to
      diagnose and manage among patients with schizophrenia. AIM: To investigate the
      prevalence and correlates of social phobia in patients with schizophrenia.
      METHOD: Diagnosis of schizophrenia and schizoaffective disorders as well as co
      morbid anxiety disorders was established according to DSM-IV and the Structured
      Clinical Interview for Diagnosis (SCID-P Hebrew version). Severity of psychotic
      symptoms and social anxiety symptoms was assessed with the Positive and Negative
      Symptom Scale (PANSS) and the Liebowitz Social Anxiety Scale (LSAS). RESULTS: The
      cohort studied included 117 patients with schizophrenia. Thirteen patients were
      diagnosed as suffering from co-morbid social phobia (11%). There was a tendency
      for patients with co-morbid social phobia to have higher severity PANSS total
      score. There was a significant correlation between the score of the LSAS ;fear'
      and PANSS positive subscales. Avoidance scores were higher among patients with
      negative signs. CONCLUSION: Co-morbidity of schizophrenia and social anxiety
      disorder is not rare among patients with schizophrenia. Treatment implications
      need be further investigated.

PMID- 19383664
TI  - Psychotic symptoms and general health in a socially disadvantaged migrant
      community in Bologna.
AB  - BACKGROUND AND AIMS: Social exclusion and reduced access to community health
      services can lead to urgent health problems among immigrants; this may explain
      their increasing rate of admittance to psychiatric inpatient units. This cross
      sectional study aims to evaluate the prevalence of psychotic symptoms among
      Romanian immigrants living in very poor conditions at an abandoned hotel in
      Bologna and to highlight the possible correlation with general health status,
      distress and socio-demographic characteristics. METHODS: The Psychosis Screening
      Questionnaire (PSQ) and General Health Questionnaire-12 (GHQ-12) were
      administered to all immigrants residing at the hotel during two index days with
      the help of a cultural mediator. Socio-demographic, migration and health
      characteristics were also collected. RESULTS: Sixty eight subjects were
      evaluated. More than 80% had left Romania for economic reasons. Of immigrants,
      57% exceeded the four-point GHQ-12 threshold of potential mental disorder and 19%
      scored positively at the PSQ. Immigrants with positive PSQ showed higher mean GHQ
      12 scores (5.9 +/- 3.5 vs. 3.8 +/- 2.75; p = 0.02). The development of post
      migration health problems significantly predicts positive PSQ cases even after
      adjusting for age, sex and GHQ-12 dichotomized score (OR = 21.2, CI = 1.1-169.4).
      CONCLUSION: This community of immigrants living in deprived conditions showed a
      high prevalence of distress and psychotic symptoms, related to health problems.
      Preventing excess of psychosis among immigrants and ethnic minorities in critical
      socio-economic conditions should mean, first and foremost, facilitating social
      integration and access to primary care.

PMID- 19383665
TI  - Mental health social work and nursing in the USA and the UK: divergent paths
      coming together?
AB  - BACKGROUND: When the mental health systems of the UK and the USA are compared,
      one of the most striking differences is that social workers are the largest
      professional group in the USA and community nurses the largest in the UK. AIM AND
      METHOD: This paper examines the history of the development of both professional
      groups in both countries, and their education and training. RESULTS: Demand,
      supply and economic factors are important influences and reasons for these
      differences. CONCLUSIONS: Both professions have critical future workforce roles,
      but further consideration needs to be given to the extent to which their skills
      and values overlap in order to inform future workforce planning, and to reduce
      the extent to which the workforce pattern in both countries risks being over
      determined by supply issues.

PMID- 19383666
TI  - Parenting support and PTSD in children of a war zone.
AB  - BACKGROUND: The protective role of parenting factors on the mental well-being of
      children exposed to war trauma remains an under-researched area. AIM: To
      establish the relationship between perceived positive parenting support and post
      traumatic stress disorder (PTSD) symptoms in children exposed to war trauma.
      METHODS: A random sample of 412 children aged 12-16 years was selected from the
      Gaza Strip and was assessed using the Gaza Traumatic Events Checklist (GTEC), the
      SCID (DSM-IV) and the Perceived Parenting Support Scale (PPSS). RESULTS:
      Palestinian children were exposed to different types of war-traumatic events. The
      number of exposed traumatic events was independently associated with the severity
      of post-traumatic symptoms scores or the diagnosis of PTSD, while perceived
      parenting support was found to act as a protective factor in this association.
      CONCLUSIONS: Interventions in war zones need to ensure the minimal possible
      disruption to communities and family units, and to involve parents in preventive
      or treatment programmes for children exposed to trauma.

PMID- 19383667
TI  - Mental disability and discriminatory practices: effects of social representations
      of the Mexican population.
AB  - BACKGROUND: The prevalence of mental disorders in Mexico is 26.1%. This shows
      that an important percentage of the population suffers from mental disability.
      Despite this the country's healthcare system does not provide the least
      acceptable standard of care for the mentally disabled. AIMS: The aim of this
      study was to describe the general population's social representations of the
      disabled and analyze their relationship with the discriminatory practices from
      the state towards the mentally ill with respect to their right to health.
      METHODS: This study was a secondary analysis of the First National Survey on
      Discrimination in Mexico. In the survey 1,437 effective interviews that comprised
      a representative sample, were obtained from people aged 18 to 60 living in rural
      and urban settings. The response rate was 76.5%. The assessment tool was a self
      administered questionnaire that yielded perceptions, attitudes, values and social
      representations about discrimination towards groups of people that supposedly
      were targets of discrimination by the general population. In the survey the
      mentally ill were included under disability. As a secondary analysis of the
      survey for the purpose of this study, we selected a subset of questions that
      provided important information about social representations of the general
      Mexican population towards persons with disabilities. The general population's
      social representations of the disabled were analyzed. RESULTS: The disabled are
      the second group after the elderly perceived as the most discriminated and
      neglected and bearing more suffering. A whole set of negative representations
      concerning the disabled, such as lack of acceptance and respect, low self
      confidence, mistreatment, incomprehension, isolation, intolerance, indifference
      and bad attitudes from others, were elicited. CONCLUSIONS: Social representations
      are social correspondents of the discriminatory practices that the state exerts
      toward the mentally ill with respect to their right to health. These
      representations serve to maintain, naturalize and legitimize these practices. All
      sectors of society should make an effort to change the negative social
      representations towards this vulnerable section of society.

PMID- 19383668
TI  - Quality of life in opium-addicted patients with coronary artery disease as
      measured with WHOQOL-BREF.
AB  - OBJECTIVE: Several factors can influence the quality of life in patients with
      coronary artery disease (CAD). The goal of this research was to measure quality
      of life in opium-addicted patients with CAD in order to assess the effect of CAD
      risk factors on their quality of life. METHOD: The WHOQOL-BREF questionnaire was
      completed through interviews with 275 patients who underwent isolated coronary
      artery bypass surgery in Tehran Heart Centre between May and September 2006.
      RESULTS: No significant differences were found in the mean scores of the four
      domains of quality of life between the addicted and non-addicted patients.
      Furthermore, the evaluation of QOL in the groups with CAD risk factors showed
      that the mean QOL domains were statistically similar between opium addicted and
      non-opium addicted patients. In the addicted group, men had a higher
      psychological health score than women. A previous history of myocardial
      infarction reduced the psychological score in this group. Also, in the addicted
      patients with a history of diabetes mellitus, social functioning was better than
      that of the non-diabetics. CONCLUSIONS: The different domains of quality of life
      in our opium-addicted and non-addicted patients with CAD were similar; and among
      all the major risk factors for coronary artery disease, only female gender and a
      previous history of myocardial infarction could influence quality of life in the
      opium-addicted patients.

PMID- 19383669
TI  - Satisfied carers of persons with enduring mental illness: who and why?
AB  - BACKGROUND: This secondary mixed-methods analysis was based on the interview data
      collected for an exploratory study of the experiences and needs of carers of
      persons with enduring mental illness. The aims were to identify and describe
      socio-demographic and contextual factors associated with the satisfaction of
      carers with family support. METHOD: Content analysis and non-parametric tests
      were used for the exploration of qualitative and quantitative data collected from
      38 carers. RESULTS: The majority of the satisfied carers were male and from a
      higher socio-economic group than other carers. The ill relatives of all satisfied
      participants resided outside their family homes. Carer satisfaction was
      associated with such categories as: a caring service; supportive and unintrusive
      family relationships; being accepted as partners; supportive community; and
      suitable family services. All the identified categories were interrelated.
      CONCLUSIONS: The identified categories and socio-demographic factors should be
      considered for inclusion in the planning and evaluation of family support
      services.

PMID- 19383670
TI  - Employment status, duration of residence and mental health among skilled migrants
      to New Zealand: results of a longitudinal study.
AB  - AIMS: To report findings on employment, duration of residence and mental health
      from a longitudinal study of 107 skilled immigrants to New Zealand from the
      People's Republic of China, India and South Africa. METHODS: Demographic and
      employment data were collected by face-to-face interviews using a structured
      questionnaire that included (as the mental health instrument) the General Health
      Questionnaire 12 (GHQ-12). The initial interview took place after the immigrants
      had been resident in New Zealand for an average of five months. Four subsequent
      interviews were conducted annually (1999-2002) on or about the anniversary of the
      first interview. RESULTS AND CONCLUSION: Rather than an initial euphoric period
      followed by a mental health crisis, the results indicated poor mental health
      status in the first two years irrespective of employment status. Thereafter,
      mental health slightly improved as did employment rates. A surprising result was
      that although the South Africans had the highest employment rate, there were
      neither substantial mental health differences among the three groups nor was
      there a significant improvement during the course of the longitudinal study.

PMID- 19383671
TI  - Adenosine sensitive focal atrial tachycardia originating from the non-coronary
      aortic cusp.
AB  - We report on the characteristics and the ablation procedure of a focal atrial
      tachycardia originating from the non-coronary aortic cusp. The
      electrophysiological features of the tachycardia included: (i) incessant pattern;
      (ii) easy induction and termination by atrial stimulation; (iii) earliest right
      atrial activation at the para-hisian area; and (iv) termination by adenosine.
      Left-sided mapping revealed the earliest atrial activation during the tachycardia
      at the non-coronary aortic cusp. Radiofrequency energy application at this site
      successfully terminated the tachycardia. Mapping of the non-coronary aortic cusp
      should always be considered when the earliest right atrial activation is recorded
      at the para-hisian area in order to avoid the risk of atrioventricular block by
      inappropriate ablation near the His-bundle region.

PMID- 19383672
TI  - Patterns of late gadolinium enhancement are associated with ventricular stiffness
      in patients with advanced non-ischaemic dilated cardiomyopathy.
AB  - AIMS: Despite the prognostic importance of ventricular filling and ventricular
      arterial interaction in patients with advanced systolic heart failure, the
      structural determinants of these parameters have not been fully studied. We aimed
      to investigate whether patterns of late gadolinium enhancement (LGE) on cardiac
      magnetic resonance affect ventricular elastic properties or performance in
      patients with non-ischaemic dilated cardiomyopathy (DCM). METHODS AND RESULTS:
      Patients (n = 49) with markedly reduced systolic function (left ventricular (LV)
      ejection fraction <35%) due to longstanding non-ischaemic DCM underwent contrast
      enhanced cardiac magnetic resonance after comprehensive echo-Doppler evaluations.
      The single beat-derived end-diastolic elastance, end-systolic elastance, arterial
      elastance, and dyssynchrony indices were measured by echo. On the basis of LGE
      patterns, patients could be divided into three groups: non-LGE (n = 18), non
      midwall LGE (n = 13), and midwall LGE (n = 18). The midwall LGE group had lower
      LV systolic longitudinal velocity (4.6 +/- 1.7 for non-LGE vs. 4.3 +/- 1.2 for
      non-midwall LGE vs. 3.5 +/- 1.0 cm/s for midwall LGE, P = 0.025), higher end
      diastolic elastance index (0.41 +/- 0.21 vs. 0.46 +/- 0.31 vs. 0.85 +/- 0.51
      respectively, P = 0.008), and a more impaired ventriculoarterial coupling index
      (3.14 +/- 1.53 vs. 2.88 +/- 1.94 vs. 5.52 +/- 3.18, P = 0.006) than other
      subgroups. CONCLUSION: Patients with midwall LGE had a higher ventricular
      stiffness index and more impaired ventriculoarterial coupling when compared with
      other non-ischaemic DCM patients.

PMID- 19383674
TI  - A permease encoded by STL1 is required for active glycerol uptake by Candida
      albicans.
AB  - Candida albicans accumulates large amounts of the polyols glycerol and d-arabitol
      when the cells are exposed to physiological conditions relevant to stress and
      virulence in animals. Intracellular concentrations of glycerol are determined by
      rates of glycerol production and catabolism and of glycerol uptake and efflux
      through the plasma membrane. We and others have studied glycerol production in C.
      albicans, but glycerol uptake by C. albicans has not been studied. In the present
      study, we found that [(14)C]glycerol uptake by C. albicans SC5314 was (i)
      accumulative; (ii) dependent on proton-motive force; (iii) unaffected by carbon
      source; and (iv) unaffected by large molar excesses of d-arabitol or other
      polyols. The respective K(m) and V(max) values were 2.1 mM and 460 micromol h(-1)
      (g dry wt)(-1) in glucose medium and 2.6 mM and 268 micromol h(-1) (g dry wt)(-1)
      in glycerol medium. To identify the C. albicans glycerol uptake protein(s), we
      cloned the C. albicans homologues of the Saccharomyces cerevisiae genes GUP1 and
      STL1, both of which are known to be involved in glycerol transport. When
      multicopy plasmids encoding C. albicans STL1, C. albicans STL2 and C. albicans
      GUP1 were introduced into the corresponding S. cerevisiae null mutants, the
      transformants all acquired the ability to grow on minimal glycerol medium;
      however, only S. cerevisiae stl1 null mutants transformed with C. albicans STL1
      actively took up extracellular [(14)C]glycerol. When both chromosomal alleles of
      C. albicans STL1 were deleted from C. albicans BWP17, the resulting stl1 null
      mutants grew poorly on minimal glycerol medium, and their ability to transport
      [(14)C]glycerol into the cell was markedly reduced. In contrast, deletion of both
      chromosomal alleles of C. albicans STL2 or of C. albicans GUP1 had no significant
      effects on [(14)C]glycerol uptake or the ability to grow on minimal glycerol
      medium. Northern blot analysis indicated that C. albicans STL1 was expressed in
      both glucose and glycerol media, conditions under which we detected wild-type
      active glycerol uptake. Furthermore, STL1 was highly expressed in salt-stressed
      cells; however, the stl1 null mutant was no more sensitive to salt stress than
      wild-type controls. We also detected high levels of STL2 expression in glycerol
      grown cells, even though deletion of this gene did not influence glycerol uptake
      activity in glycerol-grown cells. We conclude from the results above that a
      plasma-membrane H(+) symporter encoded by C. albicans STL1 actively transports
      glycerol into C. albicans cells.

PMID- 19383675
TI  - Removal of multi-heavy metals using biogenic manganese oxides generated by a deep
      sea sedimentary bacterium - Brachybacterium sp. strain Mn32.
AB  - A deep-sea manganese-oxidizing bacterium, Brachybacterium sp. strain Mn32, showed
      high Mn(II) resistance (MIC 55 mM) and Mn(II)-oxidizing/removing abilities.
      Strain Mn32 removed Mn(II) by two pathways: (1) oxidizing soluble Mn(II) to
      insoluble biogenic Mn oxides - birnessite (delta-MnO(2) group) and manganite
      (gamma-MnOOH); (2) the biogenic Mn oxides further adsorb more Mn(II) from the
      culture. The generated biogenic Mn oxides surround the cell surfaces of strain
      Mn32 and provide a high capacity to adsorb Zn(II) and Ni(II). Mn(II) oxidation by
      strain Mn32 was inhibited by both sodium azide and o-phenanthroline, suggesting
      the involvement of a metalloenzyme which was induced by Mn(II). X-ray diffraction
      analysis showed that the crystal structures of the biogenic Mn oxides were
      different from those of commercial pyrolusite (beta-MnO(2) group) and fresh
      chemically synthesized vernadite (delta-MnO(2) group). The biogenic Mn oxides
      generated by strain Mn32 showed two to three times higher Zn(II) and Ni(II)
      adsorption abilities than commercial and fresh synthetic MnO(2). The crystal
      structure and the biogenic MnO(2) types may be important factors for the high
      heavy metal adsorption ability of strain Mn32. This study provides potential
      applications of a new marine Mn(II)-oxidizing bacterium in heavy metal
      bioremediation and increases our basic knowledge of microbial manganese oxidation
      mechanisms.

PMID- 19383676
TI  - Molecular cloning and functional characterization of two CYP619 cytochrome P450s
      involved in biosynthesis of patulin in Aspergillus clavatus.
AB  - Patulin is an acetate-derived tetraketide mycotoxin produced by several fungal
      species, especially Aspergillus, Penicillium and Byssochlamys species. The health
      risks due to patulin consumption by humans have led many countries to regulate it
      in human food. Previous studies have shown the involvement of cytochrome P450
      monooxygenases in the hydroxylation of two precursors of patulin, m-cresol and m
      hydroxybenzylalcohol. In the present study, two cytochrome P450 genes were
      identified in the genome sequence of Aspergillus clavatus, a patulin-producing
      species. Both mRNAs were strongly co-expressed during patulin production.
      CYP619C2, encoded by the first gene, consists of 529 aa, while the second
      cytochrome, CYP619C3, consists of 524 aa. The coding sequences were used to
      perform the heterologous expression of functional enzymes in Saccharomyces
      cerevisiae. The bioconversion assays showed that CYP619C3 catalysed the
      hydroxylation of m-cresol to yield m-hydroxybenzyl alcohol. CYP619C2 catalysed
      the hydroxylation of m-hydroxybenzyl alcohol and m-cresol to gentisyl alcohol and
      2,5-dihydroxytoluene (toluquinol), respectively. Except for the last compound,
      all enzyme products are known precursors of patulin. Taken together, these data
      strongly suggest the involvement of CYP619C2 and CYP619C3 in the biosynthesis of
      patulin. CYP619C2 and CYP619C3 are located near to two other genes involved in
      patulin biosynthesis, namely the 6-methylsalicylic acid synthase (6msas) and
      isoepoxydon dehydrogenase (idh) genes. The current data associated with an
      analysis of the sequence of A. clavatus suggest the presence of a cluster of 15
      genes involved in patulin biosynthesis.

PMID- 19383677
TI  - Contributions of two UDP-glucose dehydrogenases to viability and polymyxin B
      resistance of Burkholderia cenocepacia.
AB  - Burkholderia cenocepacia is highly resistant to antimicrobial peptides and we
      hypothesized that the conversion of UDP-glucose to UDP-glucuronic acid, a
      reaction catalysed by the enzyme UDP-glucose dehydrogenase (Ugd) would be
      important for this resistance. The genome of B. cenocepacia contains three
      predicted ugd genes: ugd(BCAL2946), ugd(BCAM0855) and ugd(BCAM2034), all of which
      were individually inactivated. Only inactivation of ugd(BCAL2946) resulted in
      increased sensitivity to polymyxin B and this sensitivity could be overcome when
      either ugd(BCAL2946) or ugd(BCAM0855) but not ugd(BCAM2034) was expressed from
      plasmids. The growth of a conditional ugd(BCAL2946) mutant, created in the
      Deltaugd(BCAM0855) background, was significantly impaired under non-permissive
      conditions. Growth could be rescued by either ugd(BCAL2946) or ugd(BCAM0855)
      expressed in trans, but not by ugd(BCAM2034). Biochemical analysis of the
      purified, recombinant forms of Ugd(BCAL2946) and Ugd(BCAM0855) revealed that they
      are soluble homodimers with similar in vitro Ugd activity and comparable kinetic
      constants for their substrates UDP-glucose and NAD(+). Purified Ugd(BCAM2034)
      showed no in vitro Ugd activity. Real-time PCR analysis showed that the
      expression of ugd(BCAL2946) was 5.4- and 135-fold greater than that of
      ugd(BCAM0855) and ugd(BCAM2034), respectively. Together, these data indicate that
      the combined activity of Ugd(BCAL2946) and Ugd(BCAM0855) is essential for the
      survival of B. cenocepacia but only the most highly expressed ugd gene,
      ugd(BCAL2946), is required for polymyxin B resistance.

PMID- 19383678
TI  - Small heat-shock protein Hsp12 contributes to yeast tolerance to freezing stress.
AB  - The HSP12 gene encodes one of the two major small heat-shock proteins of
      Saccharomyces cerevisiae and is induced under different conditions, such as low
      and high temperatures, osmotic or oxidative stress and high sugar or ethanol
      concentrations. However, few studies could demonstrate any correlation between
      HSP12 deletion or overexpression and a phenotype of sensitivity/resistance,
      making it difficult to attribute a role for Hsp12p under several of these stress
      conditions. We investigated the possible role of Hsp12p in yeast freezing
      tolerance. Contrary to what would be expected, the hsp12 null mutant when
      subjected to prolonged storage at -20 degrees C showed an increased resistance to
      freezing when compared with the isogenic wild-type strain. Because the mutant
      strain displayed a higher intracellular trehalose concentration than the wild
      type, which could mask the effect of manipulating HSP12, we overexpressed the
      HSP12 gene in a trehalose-6-phosphate synthase (TPS1) null mutant. The tps1Delta
      strain overexpressing HSP12 showed an increase in resistance to freezing storage,
      indicating that Hsp12p plays a role in freezing tolerance in a way that seems to
      be interchangeable with trehalose. In addition, we show that overexpression of
      HSP12 in this tps1Delta strain also increased resistance to heat shock and that
      absence of HSP12 compromises the ability of yeast cells to accumulate high levels
      of trehalose in response to a mild heat stress.

PMID- 19383679
TI  - Meningococcal biofilm growth on an abiotic surface - a model for epithelial
      colonization?
AB  - Neisseria meningitidis colonizes the human nasopharynx asymptomatically, often
      for prolonged periods, but occasionally invades from this site to cause life
      threatening infection. In the nasopharynx aggregated organisms are closely
      attached to the epithelial surface, in a state in which the expression of
      components of the bacterial envelope differs significantly from that found in
      organisms multiplying exponentially in liquid phase culture or in the blood. We
      and others have hypothesized that here they are in the biofilm state, and to
      explore this we have investigated biofilm formation by the serogroup B strain
      MC58 on an abiotic surface, in a sorbarod system. Transcriptional changes were
      analysed, focusing on alteration in gene expression relevant to polysaccharide
      capsulation, lipooligosaccharide and outer-membrane protein synthesis - all
      phenotypes of importance in epithelial colonization. We report downregulation of
      genes controlling capsulation and the production of core oligosaccharide, and
      upregulation of genes encoding a range of outer-membrane components, reflecting
      phenotypic changes that have been established to occur in the colonizing state. A
      limited comparison with organisms recovered from an extended period of co
      cultivation with epithelial cells suggests that this model system may better
      mirror natural colonization than do short-term meningococcal/epithelial cell co
      cultivation systems. Modelling prolonged meningococcal colonization with a
      sorbarod system offers insight into gene expression during this important, but
      experimentally relatively inaccessible, phase of human infection.

PMID- 19383680
TI  - Characterization and subcellular localization of a bacterial flotillin homologue.
AB  - The process of endospore formation in Bacillus subtilis is complex, requiring the
      generation of two distinct cell types, a forespore and larger mother cell. The
      development of these cell types is controlled and regulated by cell type-specific
      gene expression, activated by a sigma-factor cascade. Activation of these cell
      type-specific sigma factors is coupled with the completion of polar septation.
      Here, we describe a novel protein, YuaG, a eukaryotic reggie/flotillin homologue
      that is involved in the early stages of sporulation of the Gram-positive model
      organism B. subtilis. YuaG localizes in discrete foci in the membrane and is
      highly dynamic. Purification of detergent-resistant membranes revealed that YuaG
      is associated with negatively charged phospholipids, e.g. phosphatidylglycerol
      (PG) or cardiolipin (CL). However, localization of YuaG is not always dependent
      on PG/CL in vivo. A yuaG disruption strain shows a delay in the onset of
      sporulation along with reduced sporulation efficiency, where the spores develop
      to a certain stage and then appear to be trapped at this stage. Our results
      indicate that YuaG is involved in the early stage of spore development, probably
      playing a role in the signalling cascade at the onset of sporulation.

PMID- 19383681
TI  - Transfer, stable maintenance and expression of the mycolactone polyketide
      megasynthase mls genes in a recombination-impaired Mycobacterium marinum.
AB  - The human pathogen Mycobacterium ulcerans produces a polyketide metabolite called
      mycolactone with potent immunomodulatory activity. M. ulcerans strain Agy99 has a
      174 kb plasmid called pMUM001 with three large genes (mlsA1, 51 kb; mlsA2, 7.2
      kb; mlsB, 43 kb) that encode type I polyketide synthases (PKS) required for the
      biosynthesis of mycolactone, as demonstrated by transposon mutagenesis. However,
      there have been no reports of transfer of the mls locus to another mycobacterium
      to demonstrate that these genes are sufficient for mycolactone production because
      in addition to their large size, the mls genes contain a high level of internal
      sequence repetition, such that the entire 102 kb locus is composed of only 9.5 kb
      of unique DNA. The combination of their large size and lack of stability during
      laboratory passage makes them a challenging prospect for transfer to a more
      rapidly growing and genetically tractable host. Here we describe the construction
      of two bacterial artificial chromosome Escherichia coli/Mycobacterium shuttle
      vectors, one based on the pMUM001 origin of replication bearing mlsB, and the
      other based on the mycobacteriophage L5 integrase, bearing mlsA1 and mlsA2. The
      combination of these two constructs permitted the two-step transfer of the entire
      174 kb pMUM001 plasmid to Mycobacterium marinum, a rapidly growing non
      mycolactone-producing mycobacterium that is a close genetic relative of M.
      ulcerans. To improve the stability of the mls locus in M. marinum, recA was
      inactivated by insertion of a hygromycin-resistance gene using double-crossover
      allelic exchange. As expected, the DeltarecA mutant displayed increased
      susceptibility to UV killing and a decreased frequency of homologous
      recombination. Southern hybridization and RT-PCR confirmed the stable transfer
      and expression of the mls genes in both wild-type M. marinum and the recA mutant.
      However, neither mycolactone nor its predicted precursor metabolites were
      detected in either strain. These experiments show that it is possible to
      successfully manipulate and stably transfer the large mls genes, but that other
      bacterial host factors appear to be required to facilitate mycolactone
      production.

PMID- 19383682
TI  - Kinetic characterization of the soluble butane monooxygenase from Thauera
      butanivorans, formerly 'Pseudomonas butanovora'.
AB  - Soluble butane monooxygenase (sBMO), a three-component di-iron monooxygenase
      complex expressed by the C(2)-C(9) alkane-utilizing bacterium Thauera
      butanivorans, was kinetically characterized by measuring substrate specificities
      for C(1)-C(5) alkanes and product inhibition profiles. sBMO has high sequence
      homology with soluble methane monooxygenase (sMMO) and shares a similar substrate
      range, including gaseous and liquid alkanes, aromatics, alkenes and halogenated
      xenobiotics. Results indicated that butane was the preferred substrate (defined
      by k(cat) : K(m) ratios). Relative rates of oxidation for C(1)-C(5) alkanes
      differed minimally, implying that substrate specificity is heavily influenced by
      differences in substrate K(m) values. The low micromolar K(m) for linear C(2)
      C(5) alkanes and the millimolar K(m) for methane demonstrate that sBMO is two to
      three orders of magnitude more specific for physiologically relevant substrates
      of T. butanivorans. Methanol, the product of methane oxidation and also a
      substrate itself, was found to have similar K(m) and k(cat) values to those of
      methane. This inability to kinetically discriminate between the C(1) alkane and
      C(1) alcohol is observed as a steady-state concentration of methanol during the
      two-step oxidation of methane to formaldehyde by sBMO. Unlike methanol, alcohols
      with chain length C(2)-C(5) do not compete effectively with their respective
      alkane substrates. Results from product inhibition experiments suggest that the
      geometry of the active site is optimized for linear molecules four to five
      carbons in length and is influenced by the regulatory protein component B (butane
      monooxygenase regulatory component; BMOB). The data suggest that alkane oxidation
      by sBMO is highly specialized for the turnover of C(3)-C(5) alkanes and the
      release of their respective alcohol products. Additionally, sBMO is particularly
      efficient at preventing methane oxidation during growth on linear alkanes > or
      =C(2,) despite its high sequence homology with sMMO. These results represent, to
      the best of our knowledge, the first kinetic in vitro characterization of the
      closest known homologue of sMMO.

PMID- 19383683
TI  - Identification of novel LPXTG-linked surface proteins from Streptococcus
      gordonii.
AB  - Surface adhesion plays an essential part in the survival of the commensal
      organism Streptococcus gordonii in the oral cavity as well as during
      opportunistic infections such as endocarditis. At least two types of cell surface
      protein involved in adhesion are found on the surface of Gram-positive bacteria:
      those anchored via an LPXTG motif by the enzyme sortase A (SrtA) and those
      associated with the cell surface by, as yet, unknown mechanisms. In srtA(-)
      mutants, LPXTG-containing proteins have been shown to be released rather than
      cross-linked to the cell wall. We have therefore used 2D gel electrophoresis of
      released proteins from an srtA(-) mutant as well as the wild-type strain,
      followed by peptide identification by MS, to identify a set of novel proteins
      predicted to be present on the surface of S. gordonii DL1. This includes two
      large LPXTG-linked proteins (SGO_0707 and SGO_1487), which both contain tandemly
      repeated sequences similar to those present in known fibrillar adhesins. A 5'
      nucleotidase and a protein with a putative collagen-binding domain, both
      containing LPXTG motifs, were also identified. Anchorless proteins with known
      chaperone, stress response and elongation factor functions, apparently
      responsible for bacterial binding to keratinocytes and saliva-coated surfaces in
      the absence of the LPXTG-linked adhesins, were also associated with the cell
      surface. These data reveal a range of proteins to be present on the S. gordonii
      DL1 cell surface, the expression of which plays an important role in adhesion to
      epithelia and which represent likely candidates for novel virulence factors in S.
      gordonii.

PMID- 19383684
TI  - The ecology, epidemiology and virulence of Enterococcus.
AB  - Enterococci are Gram-positive, catalase-negative, non-spore-forming, facultative
      anaerobic bacteria, which usually inhabit the alimentary tract of humans in
      addition to being isolated from environmental and animal sources. They are able
      to survive a range of stresses and hostile environments, including those of
      extreme temperature (5-65 degrees C), pH (4.5-10.0) and high NaCl concentration,
      enabling them to colonize a wide range of niches. Virulence factors of
      enterococci include the extracellular protein Esp and aggregation substances
      (Agg), both of which aid in colonization of the host. The nosocomial
      pathogenicity of enterococci has emerged in recent years, as well as increasing
      resistance to glycopeptide antibiotics. Understanding the ecology, epidemiology
      and virulence of Enterococcus species is important for limiting urinary tract
      infections, hepatobiliary sepsis, endocarditis, surgical wound infection,
      bacteraemia and neonatal sepsis, and also stemming the further development of
      antibiotic resistance.

PMID- 19383685
TI  - The GPI-modified proteins Pga59 and Pga62 of Candida albicans are required for
      cell wall integrity.
AB  - The fungal cell wall is essential in maintaining cellular integrity and plays key
      roles in the interplay between fungal pathogens and their hosts. The PGA59 and
      PGA62 genes encode two short and related glycosylphosphatidylinositol-anchored
      cell wall proteins and their expression has been previously shown to be strongly
      upregulated when the human pathogen Candida albicans grows as biofilms. Using GFP
      fusion proteins, we have shown that Pga59 and Pga62 are cell-wall-located, N- and
      O-glycosylated proteins. The characterization of C. albicans
      pga59Delta/pga59Delta, pga62Delta/pga62Delta and pga59Delta/pga59Delta
      pga62Delta/pga62Delta mutants suggested a minor role of these two proteins in
      hyphal morphogenesis and that they are not critical to biofilm formation.
      Importantly, the sensitivity to different cell-wall-perturbing agents was altered
      in these mutants. In particular, simultaneous inactivation of PGA59 and PGA62
      resulted in high sensitivity to Calcofluor white, Congo red and nikkomicin Z and
      in resistance to caspofungin. Furthermore, cell wall composition and observation
      by transmission electron microscopy indicated an altered cell wall structure in
      the mutant strains. Collectively, these data suggest that the cell wall proteins
      Pga59 and Pga62 contribute to cell wall stability and structure.

PMID- 19383686
TI  - Homocysteine editing and growth inhibition in Escherichia coli.
AB  - In Escherichia coli homocysteine (Hcy) is metabolically converted to the
      thioester Hcy-thiolactone in ATP-consuming reactions catalysed by methionyl-,
      isoleucyl- and leucyl-tRNA synthetases. Here we show that growth inhibition
      caused by supplementation of E. coli cultures with Hcy is accompanied by greatly
      increased accumulation of Hcy-thiolactone. Energy dissipation for Hcy editing
      increases 100-fold in the presence of exogenous Hcy and reaches one mole of ATP
      unproductively dissipated for Hcy-thiolactone synthesis per each mole of ATP that
      is consumed for methionine activation. Inhibiting Hcy-thiolactone synthesis with
      isoleucine, leucine or methionine accelerates bacterial growth in Hcy
      supplemented cultures. Growth rates in Hcy-inhibited cultures are inversely
      related to the accumulation of Hcy-thiolactone. We also show that the levels of
      protein N-linked Hcy modestly increase in E. coli cells in Hcy-supplemented
      cultures. The results suggest that Hcy editing restrains bacterial growth.

PMID- 19383687
TI  - polR, a pathway-specific transcriptional regulatory gene, positively controls
      polyoxin biosynthesis in Streptomyces cacaoi subsp. asoensis.
AB  - The polyoxin (POL) biosynthetic gene cluster (pol) was recently cloned from
      Streptomyces cacaoi subsp. asoensis. A 3.3 kb DNA fragment carrying an obvious
      open reading frame (polR), whose deduced product shows sequence similarity to
      SanG of Streptomyces ansochromogenes and PimR of Streptomyces natalensis, was
      revealed within the pol gene cluster. Disruption of polR abolished POL
      production, which could be complemented by the integration of a single copy of
      polR into the chromosome of the non-producing mutant. The introduction of an
      extra copy of polR in the wild-type strain resulted in increased production of
      POLs. The transcription start point (tsp) of polR was determined by S1 mapping.
      Reverse transcriptase PCR experiments showed that PolR is required for the
      transcription of 18 structural genes in the pol gene cluster. Furthermore, we
      showed that polC and polB, the respective first genes of two putative operons
      (polC-polQ2 and polA-polB) consisting of 16 and 2 of these 18 genes, have similar
      promoter structures. Gel retardation assays indicated that PolR has specific DNA
      binding activity for the promoter regions of polC and polB. Our data suggest that
      PolR acts in a positive manner to regulate POL production by activating the
      transcription of at least two putative operons in the pol gene cluster.

PMID- 19383688
TI  - Effect of FliK mutation on the transcriptional activity of the {sigma}54 sigma
      factor RpoN in Helicobacter pylori.
AB  - Helicobacter pylori is a motile Gram-negative bacterium that colonizes and
      persists in the human gastric mucosa. The flagellum gene regulatory circuitry of
      H. pylori is unique in many aspects compared with the Salmonella/Escherichia coli
      paradigms, and some regulatory checkpoints remain unclear. FliK controls the hook
      length during flagellar assembly. Microarray analysis of a fliK-null mutant
      revealed increased transcription of genes under the control of the sigma(54)
      sigma factor RpoN. This sigma factor has been shown to be responsible for
      transcription of the class II flagellar genes, including flgE and flaB. No genes
      higher in the flagellar hierarchy had altered expression, suggesting specific and
      localized FliK-dependent feedback on the RpoN regulon. FliK thus appears to be
      involved in three processes: hook-length control, export substrate specificity
      and control of RpoN transcriptional activity.

PMID- 19383689
TI  - The cmaR gene of Corynebacterium ammoniagenes performs a novel regulatory role in
      the metabolism of sulfur-containing amino acids.
AB  - A novel regulatory gene, which performs an essential function in sulfur
      metabolism, has been identified in Corynebacterium ammoniagenes and was
      designated cmaR (cysteine and methionine regulator in C. ammoniagenes). The cmaR
      disrupted strain (DeltacmaR) lost the ability to grow on minimal medium, and was
      identified as a methionine and cysteine double auxotroph. The mutant strain
      proved unable to convert cysteine to methionine (and vice versa), and lost the
      ability to assimilate and reduce sulfate to sulfide. In the DeltacmaR strain, the
      mRNAs of the methionine biosynthetic genes metYX, metB and metFE were
      significantly reduced, and the activities of the methionine biosynthetic enzymes
      cystathionine gamma-synthase, O-acetylhomoserine sulfhydrylase, and cystathionine
      beta-lyase were relatively low, thereby suggesting that the cmaR gene exerts a
      positive regulatory effect on methionine biosynthetic genes. In addition, with
      the exception of cysK, reduced transcription levels of the sulfur-assimilatory
      genes cysIXYZ and cysHDN were noted in the cmaR-disrupted strain, which suggests
      that sulfur assimilation is also under the positive control of the cmaR gene.
      Furthermore, the expression of the cmaR gene itself was strongly induced via the
      addition of cysteine or methionine alone, but not the introduction of both amino
      acids together to the growth medium. In addition, the expression of the cmaR gene
      was enhanced in an mcbR-disrupted strain, which suggests that cmaR is under the
      negative control of McbR, which has been identified as a global regulator of
      sulfur metabolism. DNA binding of the purified CmaR protein to the promoter
      region of its target genes could be demonstrated in vitro. No metabolite effector
      was required for the protein to bind DNA. These results demonstrated that the
      cmaR gene of C. ammoniagenes plays a role similar to but distinct from that of
      the functional homologue cysR of Corynebacterium glutamicum.

PMID- 19383690
TI  - Tellurite-mediated disabling of [4Fe-4S] clusters of Escherichia coli
      dehydratases.
AB  - The tellurium oxyanion tellurite is toxic for most organisms and it seems to
      alter a number of intracellular targets. In this work the toxic effects of
      tellurite upon Escherichia coli [4Fe-4S] cluster-containing dehydratases was
      studied. Reactive oxygen species (ROS)-sensitive fumarase A (FumA) and aconitase
      B (AcnB) as well as ROS-resistant fumarase C (FumC) and aconitase A (AcnA) were
      assayed in cell-free extracts from tellurite-exposed cells in both the presence
      and absence of oxygen. While over 90 % of FumA and AcnB activities were lost in
      the presence of oxygen, no enzyme inactivation was observed in anaerobiosis. This
      result was not dependent upon protein biosynthesis, as determined using
      translation-arrested cells. Enzyme activity of purified FumA and AcnB was
      inhibited when exposed to an in vitro superoxide-generating, tellurite-reducing
      system (ITRS). No inhibitory effect was observed when tellurite was omitted from
      the ITRS. In vivo and in vitro reconstitution experiments with tellurite-damaged
      FumA and AcnB suggested that tellurite effects involve [Fe-S] cluster disabling.
      In fact, after exposing FumA to ITRS, released ferrous ion from the enzyme was
      demonstrated by spectroscopic analysis using the specific Fe(2+) chelator 2,2'
      bipyridyl. Subsequent spectroscopic paramagnetic resonance analysis of FumA
      exposed to ITRS showed the characteristic signal of an oxidatively inactivated
      [3Fe-4S](+) cluster. These results suggest that tellurite inactivates enzymes of
      this kind via a superoxide-dependent disabling of their [4Fe-4S] catalytic
      clusters.

PMID- 19383691
TI  - Population heterogeneity in Methylobacterium extorquens AM1.
AB  - Heterogeneity of cells within exponentially growing populations was addressed in
      a bacterium, the facultative methylotroph Methylobacterium extorquens AM1. A
      transcriptional fusion between a well-characterized methanol-inducible promoter
      (P(mxaF)) and gfp(uv) was used with flow cytometry to analyse the distribution of
      gene expression in populations grown on either succinate or methanol, correlated
      with forward scatter as a measure of cell size. These cell populations were found
      to consist of three major subpopulations defined by cells that were actively
      growing and dividing, newly divided, and non-dividing. Through the use of flow
      cytometry, it was demonstrated that a significant percentage of the total
      population did not respond to carbon shift. In addition, these experiments
      demonstrated that a small subset of the total population was significantly
      brighter than the rest of the population and dominated fluorimetry data. These
      results were corroborated with a continuous flow-through system and laser
      scanning microscopy, confirming that subpopulations, not discernible in the
      population average, dominate population response. These results demonstrate that
      the combination of flow cytometry and microscopic single-cell analysis can be
      effectively used to determine the dynamics of subpopulations in population
      response. In addition, they support the concept that physiological diversity in
      isogenic populations can poise some proportion of the population to respond
      appropriately to changing conditions.

PMID- 19383692
TI  - Analysis of CRISPR in Streptococcus mutans suggests frequent occurrence of
      acquired immunity against infection by M102-like bacteriophages.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) consist of
      highly conserved direct repeats interspersed with variable spacer sequences. They
      can protect bacteria against invasion by foreign DNA elements. The genome
      sequence of Streptococcus mutans strain UA159 contains two CRISPR loci,
      designated CRISPR1 and CRISPR2. The aims of this study were to analyse the
      organization of CRISPR in further S. mutans strains and to investigate the
      importance of CRISPR in acquired immunity to M102-like phages. The sequences of
      CRISPR1 and CRISPR2 arrays were determined for 29 S. mutans strains from
      different persons. More than half of the CRISPR1 spacers and about 35 % of the
      CRISPR2 spacers showed sequence similarity with the genome sequence of M102, a
      virulent siphophage specific for S. mutans. Although only a few spacers matched
      the phage sequence completely, most of the mismatches had no effect on the amino
      acid sequences of the phage-encoded proteins. The results suggest that S. mutans
      is often attacked by M102-like bacteriophages, and that its acquisition of novel
      phage-derived CRISPR sequences goes along with the presence of S. mutans phages
      in the environment. Analysis of CRISPR1 of M102-resistant mutants of S. mutans
      OMZ 381 showed that some of them had acquired novel spacers, and the sequences of
      all but one of these matched the phage M102 genome sequence. This suggests that
      the acquisition of the spacers contributed to the resistance against phage
      infection. However, since not all resistant mutants had new spacers, and since
      the removal of the CRISPR1 array in one of the mutants and in wild-type strains
      did not lead to loss of resistance to infection by M102, the acquisition of
      resistance must be based on further elements as well.

PMID- 19383693
TI  - Effects of altered TatC proteins on protein secretion efficiency via the twin
      arginine translocation pathway of Bacillus subtilis.
AB  - Protein translocation via the Tat machinery in thylakoids and bacteria occurs
      through a cooperation between the TatA, TatB and TatC subunits, of which the TatC
      protein forms the initial Tat substrate-binding site. The Bacillus subtilis Tat
      machinery lacks TatB and comprises two separate TatAC complexes with distinct
      substrate specificities: PhoD is secreted by the TatAdCd complex, whereas YwbN is
      secreted by the TatAyCy complex. To study the role of the Gram-positive TatC
      proteins in Tat-dependent protein secretion efficiency, we applied several
      genetic engineering approaches to modify and analyse the B. subtilis TatCd and
      TatCy proteins. Cytoplasmic and transmembrane domain exchange between TatCd and
      TatCy resulted in stable chimeric proteins that were unable to secrete both known
      substrates of the B. subtilis Tat system. Site-directed mutagenesis of conserved
      residues in the N-terminal part of both TatC proteins revealed significant
      differences in the degree of importance of these residues between TatCd, TatCy
      and Escherichia coli TatC. In addition, two small C-terminal deletions in TatCy
      completely abolished YwbN translocation, indicating that this terminus is
      essential for Tat translocation activity. Important differences from previous
      observations for E. coli TatC and implications for substrate binding and
      translocation are discussed.

PMID- 19383694
TI  - Cloning of feather-degrading minor extracellular protease from Bacillus cereus
      DCUW: dissection of the structural domains.
AB  - Bacterial extracellular proteases play an important role in cell survival and
      cell-cell communication. A high-molecular-mass minor extracellular protease (Vpr)
      from a feather-degrading bacterium, Bacillus cereus DCUW, has been reported by
      our laboratory. In the present study, we cloned and expressed Vpr in Escherichia
      coli. Complete nucleotide sequencing of this gene predicted that the protease is
      a member of the serine protease family, and smart domain analysis revealed that
      the protease consists of an N-terminal signal sequence for secretion, a
      subtilisin_N sequence that is a signature for N-terminal processing, a catalytic
      S_8 peptidase domain, and finally a long C-terminal protease-associated (PA)
      region containing nine intrinsically disordered subdomains. Four truncated
      constructs of the Vpr protease were cloned and expressed in E. coli. We found
      that the catalytic domain (amino acid residues 172-583) is sufficient for
      protease activity. Maturation of the Vpr protease needed both N-terminal and C
      terminal processing. We have demonstrated that the oligomerization property is
      associated with the C-terminal protease-associated domain and also shown that the
      substrate-binding specificity to raw feather resides in this domain.

PMID- 19383695
TI  - Raman spectroscopic typing reveals the presence of carotenoids in Mycoplasma
      pneumoniae.
AB  - Raman spectroscopy has previously been demonstrated to be a highly useful
      methodology for the identification and/or typing of micro-organisms. In this
      study, we set out to evaluate whether this technology could also be applied as a
      tool to discriminate between isolates of Mycoplasma pneumoniae, which is
      generally considered to be a genetically highly uniform species. In this
      evaluation, a total of 104 strains of M. pneumoniae were analysed, including two
      reference strains (strains M129 and FH), and 102 clinical isolates, which were
      isolated between 1973 and 2005 and originated from various countries. By Raman
      spectral analysis (Raman typing) of this strain collection, we were able to
      reproducibly distinguish six different clusters of strains. An unequivocal
      correlation between Raman typing and P1 genotyping, which is based on sequence
      differences in the P1 (or MPN141) gene of M. pneumoniae, was not observed. In the
      two major Raman clusters that we identified (clusters 3 and 6, which together
      harboured 81 % of the strains), the different P1 subtypes were similarly
      distributed, and approximately 76 % isolates were of subtype 1, approximately 20
      % of subtype 2 and approximately 5 % of variant 2a. Nevertheless, a relatively
      high prevalence of P1 subtype 2 strains was found in clusters 2 and 5 (100 %), as
      well as in cluster 1 (75 %) and cluster 4 (71 %); these clusters, however,
      harboured a small number of strains. Only two of the strains (2 %) could not be
      typed correctly. Interestingly, analysis of the Raman spectra revealed the
      presence of carotenoids in M. pneumoniae. This finding is in line with the
      identification of M. pneumoniae genes that have similarity with genes involved in
      a biochemical pathway leading to carotenoid synthesis, i.e. the 2-C-methyl-d
      erythritol 4-phosphate (MEP) pathway. Therefore, we hypothesize that M.
      pneumoniae hosts an MEP-like pathway for carotenoid synthesis. We conclude that
      Raman spectroscopy is a convenient tool for discriminating between M. pneumoniae
      strains, and that it presents a promising supplement to the current methods for
      typing of this bacterium.

PMID- 19383696
TI  - Folding and trimerization of signal sequence-less mature TolC in the cytoplasm of
      Escherichia coli.
AB  - TolC is a multifunctional outer-membrane protein (OMP) of Escherichia coli that
      folds into a unique alpha/beta-barrel structure. Previous studies have shown that
      unlike the biogenesis of beta-barrel OMPs, such as porins, TolC assembles
      independently from known periplasmic folding factors. Yet, the assembly of TolC,
      like that of beta-barrel OMPs, is dependent on BamA and BamD, two essential
      components of the beta-barrel OMP assembly machinery. We have investigated the
      folding properties and cellular trafficking of a TolC derivative that lacks the
      entire signal sequence (TolCDelta2-22). A significant amount of TolCDelta2-22 was
      found to be soluble in the cytoplasm, and a fraction of it folded and trimerized
      into a conformation similar to that of the normal outer membrane-localized TolC
      protein. Some TolCDelta2-22 was found to associate with membranes, but failed to
      assume a wild-type-like folded conformation. The null phenotype of TolCDelta2-22
      was exploited to isolate suppressor mutations, the majority of which mapped in
      secY. In the secY suppressor background, TolCDelta2-22 resumed normal function
      and folded like wild-type TolC. Proper membrane insertion could not be achieved
      upon in vitro incubation of cytoplasmically folded TolCDelta2-22 with purified
      outer membrane vesicles, showing that even though TolC is intrinsically capable
      of folding and trimerization, for successful integration into the outer membrane
      these events need to be tightly coupled to the insertion process, which is
      mediated by the Bam machinery. Genetic and biochemical data attribute the unique
      folding and assembly pathways of TolC to its large soluble alpha-helical domain.

PMID- 19383697
TI  - Two novel metal-independent long-chain alkyl alcohol dehydrogenases from
      Geobacillus thermodenitrificans NG80-2.
AB  - Two alkyl alcohol dehydrogenase (ADH) genes from the long-chain alkane-degrading
      strain Geobacillus thermodenitrificans NG80-2 were characterized in vitro. ADH1
      and ADH2 were prepared heterologously in Escherichia coli as a homooctameric and
      a homodimeric protein, respectively. Both ADHs can oxidize a broad range of alkyl
      alcohols up to at least C(30), as well as 1,3-propanediol and acetaldehyde. ADH1
      also oxidizes glycerol, and ADH2 oxidizes isopropyl alcohol, isoamylol, acetone,
      octanal and decanal. The best substrate is ethanol for ADH1 and 1-octanol for
      ADH2. For both ADHs, the optimum assay condition is at 60 degrees C and pH 8.0,
      and both NAD and NADP can be used as the cofactor. Sequence analysis reveals that
      ADH1 and ADH2 belong to the Fe-containing/activated long-chain ADHs. However, the
      two enzymes contain neither Fe nor other metals, and Fe is not required for the
      activity, suggesting a new type of ADH. The ADHs characterized here are
      potentially useful in crude oil bioremediation and other bioconversion processes.

PMID- 19383698
TI  - LuxR-family 'solos': bachelor sensors/regulators of signalling molecules.
AB  - N-Acylhomoserine lactone (AHL) quorum-sensing (QS) signalling is the best
      understood chemical language in proteobacteria. In the last 15 years a large
      amount of research in several bacterial species has revealed in detail the
      genetic, molecular and biochemical mechanisms underlying AHL signalling. These
      studies have revealed the role played by protein pairs of the AHL synthase
      belonging to the LuxI family and cognate LuxR-family AHL sensor-regulator.
      Proteobacteria however commonly possess a QS LuxR-family protein for which there
      is no obvious cognate LuxI synthase; these proteins are found in bacteria which
      possess a complete AHL QS system(s) as well as in bacteria that do not.
      Scientists are beginning to address the roles played by these proteins and it is
      emerging that they could allow bacteria to respond to endogenous and exogenous
      signals produced by their neighbours. AHL QS research thus far has mainly focused
      on a cell-density response involving laboratory monoculture studies. Recent
      findings on the role played by the unpaired LuxR-family proteins highlight the
      need to address bacterial behaviour and response to signals in mixed communities.
      Here we review recent progress with respect to these LuxR proteins, which we
      propose to call LuxR 'solos' since they act on their own without the need for a
      cognate signal generator. Initial investigations have revealed that LuxR solos
      have diverse roles in bacterial interspecies and interkingdom communication.

PMID- 19383699
TI  - Phosphate and carbon source regulation of two PhoP-dependent
      glycerophosphodiester phosphodiesterase genes of Streptomyces coelicolor.
AB  - Glycerophosphodiesters are formed by deacylation of phospholipids. Streptomyces
      coelicolor and other soil-dwelling actinomycetes utilize glycerophosphodiesters
      as phosphate and carbon sources by the action of glycerophosphodiester
      phosphodiesterases (GDPDs). Seven genes encoding putative GDPDs occur in the S.
      coelicolor genome. Two of these genes, glpQ1 and glpQ2, encoding extracellular
      GDPDs, showed a PhoP-dependent upregulated profile in response to phosphate
      shiftdown. Expression studies using the luxAB genes as reporter confirmed the
      PhoP dependence of both glpQ1 and glpQ2. Footprinting analyses with pure GST-PhoP
      of the glpQ1 promoter revealed four protected direct repeat units (DRu). PhoP
      binding affinity to the glpQ2 promoter was lower and revealed a protected region
      containing five DRu. As expected for pho regulon genes, inorganic phosphate, and
      also glycerol 3-phosphate, inhibited the expression from both glpQ1 and glpQ2.
      The expression of glpQ1 was also repressed by serine and inositol but expression
      of glpQ2 was not. In contrast, glucose, fructose and glycerol increased
      expression of glpQ2 but not that of glpQ1. In summary, our results suggest an
      interaction of phosphate control mediated by PhoP and carbon source regulation of
      the glpQ1 and glpQ2 genes involving complex operator structures.

PMID- 19383700
TI  - Survival of uropathogenic Escherichia coli in the murine urinary tract is
      dependent on OmpR.
AB  - Uropathogenic Escherichia coli (UPEC) can grow in environments with significantly
      elevated osmolarities, such as murine and human urinary tracts. OmpR is the
      response regulator part of a two-component OmpR-EnvZ regulatory system that
      responds to osmotic stresses. To determine the role of OmpR in UPEC survival, a
      DeltaompR mutant was created in the UPEC clinical isolate NU149. The DeltaompR
      mutant had a growth defect compared with the wild-type strain under osmotic
      stress conditions; this defect was complemented by the full-length ompR gene on a
      plasmid, but not with a mutant OmpR with an alanine substitution for aspartic
      acid at the phosphorylation site at position 55. Furthermore, the DeltaompR
      mutant displayed up to 2-log reduction in bacterial cell numbers in murine
      bladders and kidneys compared with wild-type bacteria after 5 days of infection.
      The ability of the bacteria to survive was restored to wild-type levels when the
      DeltaompR mutant strain was complemented with wild-type ompR, but not when the
      alanine-substituted ompR gene was used. This study has fulfilled molecular Koch's
      postulates by showing the pivotal role OmpR plays in UPEC survival within the
      murine urinary tract.

PMID- 19383701
TI  - FimH alleles direct preferential binding of Salmonella to distinct mammalian
      cells or to avian cells.
AB  - This study aimed to determine whether allelic variants of the FimH adhesin from
      Salmonella enterica confer differential bacterial binding to different types of
      mammalian cells [murine bone marrow-derived dendritic cells (DCs) and HEp-2
      cells] and chicken leukocytes. Although the type 1 fimbriated S. enterica serovar
      Typhimurium strains AJB3 (SR-11 derivative) and SL1344 both aggregated yeast
      cells, only the former bound efficiently to DCs and HEp-2 cells. Type 1 fimbriae
      mediated binding to DCs having previously been shown to require the FimH adhesin
      and to be inhibited by mannose, FimH sequences from strains SL1344 and AJB3 were
      compared and found to differ by only one residue, asparagine 158 in SL1344 being
      replaced by a tyrosine in AJB3. The importance of residue 158 for FimH-mediated
      binding was further confirmed in recombinant Escherichia coli expressing S.
      enterica type 1 fimbriae with a variety of substitutions engineered at this
      position. Additional studies with the 'non-adhesive' FimH of a type 2 fimbriated
      S. enterica serovar Gallinarum showed that this FimH did not mediate bacterial
      binding to murine DCs or HEp-2 cells. However, the type 2 FimH significantly
      improved bacterial adhesion to chicken leukocytes, in comparison to the type 1
      FimH of strain AJB3, attributing for the first time a function to the type 2
      fimbriae of S. enterica. Consequently, our data show that allelic variation of
      the S. enterica FimH adhesin directs not only host-cell-specific recognition, but
      also distinctive binding to mammalian or avian receptors. It is most relevant
      that this allele-specific binding profile parallels the host specificity of the
      respective FimH-expressing pathogen.

PMID- 19383702
TI  - Pseudomonas aeruginosa Las quorum sensing autoinducer suppresses growth and
      biofilm production in Legionella species.
AB  - Bacteria commonly communicate with each other by a cell-to-cell signalling
      mechanism known as quorum sensing (QS). Recent studies have shown that the Las QS
      autoinducer N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C(12)-HSL) of
      Pseudomonas aeruginosa performs a variety of functions not only in intraspecies
      communication, but also in interspecies and interkingdom interactions. In this
      study, we report the effects of Pseudomonas 3-oxo-C(12)-HSL on the growth and
      suppression of virulence factors in other bacterial species that frequently co
      exist with Ps. aeruginosa in nature. It was found that 3-oxo-C(12)-HSL, but not
      its analogues, suppressed the growth of Legionella pneumophila in a dose
      dependent manner. However, 3-oxo-C(12)-HSL did not exhibit a growth-suppressive
      effect on Serratia marcescens, Proteus mirabilis, Escherichia coli, Alcaligenes
      faecalis and Stenotrophomonas maltophilia. A concentration of 50 microM 3-oxo
      C(12)-HSL completely inhibited the growth of L. pneumophila. Additionally, a
      significant suppression of biofilm formation was demonstrated in L. pneumophila
      exposed to 3-oxo-C(12)-HSL. Our results suggest that the Pseudomonas QS
      autoinducer 3-oxo-C(12)-HSL exerts both bacteriostatic and virulence factor
      suppressive activities on L. pneumophila alone.

PMID- 19383703
TI  - Galleria mellonella as an alternative infection model for Yersinia
      pseudotuberculosis.
AB  - We report that larvae of the wax moth (Galleria mellonella) are susceptible to
      infection with the human enteropathogen Yersinia pseudotuberculosis at 37 degrees
      C. Confocal microscopy demonstrated that in the initial stages of infection the
      bacteria were taken up into haemocytes. To evaluate the utility of this model for
      screening Y. pseudotuberculosis mutants we constructed and tested a superoxide
      dismutase C (sodC) mutant. This mutant showed increased susceptibility to
      superoxide, a key mechanism of killing in insect haemocytes and mammalian
      phagocytes. It showed reduced virulence in the murine yersiniosis infection model
      and in contrast to the wild-type strain IP32953 was unable to kill G. mellonella.
      The complemented mutant regained all phenotypic properties associated with SodC,
      confirming the important role of this metalloenzyme in two Y. pseudotuberculosis
      infection models.

PMID- 19383704
TI  - Simultaneous lack of catalase and beta-toxin in Staphylococcus aureus leads to
      increased intracellular survival in macrophages and epithelial cells and to
      attenuated virulence in murine and ovine models.
AB  - Staphylococcus aureus produces a variety of virulence factors that allow it to
      cause a wide range of infections in humans and animals. In the latter, S. aureus
      is a leading cause of intramammary infections. The contribution of catalase
      (KatA), an enzyme implicated in oxidative stress resistance, and beta-toxin
      (Hlb), a haemolysin, to the pathogenesis of S. aureus is poorly characterized. To
      investigate the role of these enzymes as potential virulence factors in S.
      aureus, we examined the intracellular survival of DeltakatA, Deltahlb and
      DeltakatA Deltahlb mutants in murine macrophages (J774A.1) and bovine mammary
      epithelial cells (MAC-T), and their virulence in different murine and ovine
      models. Catalase was not required for the survival of S. aureus within either
      J774A.1 or MAC-T cells. However, it was necessary for the intracellular
      proliferation of the bacterium after invasion of MAC-T cells. In addition,
      catalase was not needed for the full virulence of S. aureus in mice. Deletion of
      the hlb gene had no effect on the intracellular survival of S. aureus in J774A.1
      cells but did cause a slight increase in survival in MAC-T cells. Furthermore,
      like catalase, beta-toxin was not required for complete virulence of S. aureus in
      murine models. Unexpectedly, the DeltakatA Deltahlb mutant showed a notably
      increased persistence in both cell lines, and was significantly less virulent for
      mice than were the wild-type strain and single mutants. Most interestingly, it
      was also markedly attenuated in intramammary and subcutaneous infections in ewes
      and lambs.

PMID- 19383705
TI  - Mitochondrial nucleoids from the yeast Candida parapsilosis: expansion of the
      repertoire of proteins associated with mitochondrial DNA.
AB  - Molecules of mitochondrial DNA (mtDNA) are packed into nucleic acid-protein
      complexes termed mitochondrial nucleoids (mt-nucleoids). In this study, we
      analysed mt-nucleoids of the yeast Candida parapsilosis, which harbours a linear
      form of the mitochondrial genome. To identify conserved as well as specific
      features of mt-nucleoids in this species, we employed two strategies for analysis
      of their components. First, we investigated the protein composition of mt
      nucleoids isolated from C. parapsilosis mitochondria, determined N-terminal amino
      acid sequences of 14 proteins associated with the mt-nucleoids and identified
      corresponding genes. Next, we complemented the list of mt-nucleoid components
      with additional candidates identified in the complete genome sequence of C.
      parapsilosis as homologues of Saccharomyces cerevisiae mt-nucleoid proteins. Our
      approach revealed several known mt-nucleoid proteins as well as additional
      components that expand the repertoire of proteins associated with these
      cytological structures. In particular, we identified and purified the protein
      Gcf1, which is abundant in the mt-nucleoids and exhibits structural features in
      common with the mtDNA packaging protein Abf2 from S. cerevisiae. We demonstrate
      that Gcf1p co-localizes with mtDNA, has DNA-binding activity in vitro, and is
      able to stabilize mtDNA in the S. cerevisiae Deltaabf2 mutant, all of which
      points to a role in the maintenance of the C. parapsilosis mitochondrial genome.
      Importantly, in contrast to Abf2p, in silico analysis of Gcf1p predicted the
      presence of a coiled-coil domain and a single high-mobility group (HMG) box,
      suggesting that it represents a novel type of mitochondrial HMG protein.

PMID- 19383707
TI  - Functional characterization of FlgM in the regulation of flagellar synthesis and
      motility in Yersinia pseudotuberculosis.
AB  - We describe here the functional characterization of the flgM gene in Yersinia
      pseudotuberculosis. Direct interaction of FlgM with the alternative sigma factor
      sigma(28) (FliA) was first confirmed. A conserved region in the C-terminus of
      FlgM was found which included the sigma(28) binding domain. By site-directed
      mutagenesis, bacterial two-hybrid analysis and Western blotting, the primary FlgM
      binding sites with sigma(28) were shown to be Ile85, Ala86 and Leu89. A role for
      FlgM in swimming motility was demonstrated by inactivation of flgM and subsequent
      complementation in trans. Transcriptional fusion analyses showed differential
      gene expression of flhDC, fliA, flgM and fliC in the fliA and flgM mutants
      compared with the wild-type. flhDC expression was not influenced by sigma(28) or
      FlgM while fliA expression was abolished in the fliA mutant and considerably
      reduced in the flgM mutant when compared to the wild-type, indicating that both
      FliA and FlgM can activate fliA transcription. Conversely, flgM transcription was
      higher in the fliA mutant when compared to the wild-type, suggesting that flgM
      transcription was repressed by sigma(28). Interestingly, fliC expression was
      markedly increased in the flgM mutant, suggesting a negative regulatory role for
      FlgM in fliC expression. The transcription of other sigma-dependent genes (cheW,
      flgD, flaA, csrA and fliZ) was also examined in fliA and flgM mutant backgrounds
      and this revealed that other sigma-factors apart from sigma(28) may be involved
      in flagellar biogenesis in Y. pseudotuberculosis. Taking together the motility
      phenotypes and effects of flgM mutation on the regulation of these key motility
      genes, we propose that the mechanisms regulating flagellar biogenesis in Y.
      pseudotuberculosis may differ from those described for other bacteria.

PMID- 19383706
TI  - From a consortium sequence to a unified sequence: the Bacillus subtilis 168
      reference genome a decade later.
AB  - Comparative genomics is the cornerstone of identification of gene functions. The
      immense number of living organisms precludes experimental identification of
      functions except in a handful of model organisms. The bacterial domain is split
      into large branches, among which the Firmicutes occupy a considerable space.
      Bacillus subtilis has been the model of Firmicutes for decades and its genome has
      been a reference for more than 10 years. Sequencing the genome involved more than
      30 laboratories, with different expertises, in a attempt to make the most of the
      experimental information that could be associated with the sequence. This had the
      expected drawback that the sequencing expertise was quite varied among the groups
      involved, especially at a time when sequencing genomes was extremely hard work.
      The recent development of very efficient, fast and accurate sequencing
      techniques, in parallel with the development of high-level annotation platforms,
      motivated the present resequencing work. The updated sequence has been
      reannotated in agreement with the UniProt protein knowledge base, keeping in
      perspective the split between the paleome (genes necessary for sustaining and
      perpetuating life) and the cenome (genes required for occupation of a niche,
      suggesting here that B. subtilis is an epiphyte). This should permit
      investigators to make reliable inferences to prepare validation experiments in a
      variety of domains of bacterial growth and development as well as build up
      accurate phylogenies.

PMID- 19383708
TI  - Impact of lgt mutation on lipoprotein biosynthesis and in vitro phenotypes of
      Streptococcus agalactiae.
AB  - Although Streptococcus agalactiae, the group B Streptococcus, is a leading cause
      of invasive neonatal disease worldwide the molecular basis of its virulence is
      still poorly understood. To investigate the role of lipoproteins in the
      physiology and interaction of this pathogen with host cells, we generated a
      mutant S. agalactiae strain (A909DeltaLgt) deficient in the Lgt enzyme and thus
      unable to lipidate lipoprotein precursors (pro-lipoproteins). The loss of pro
      lipoprotein lipidation did not affect the viability of S. agalactiae or its
      growth in several different media, including cation-depleted media. The
      processing of two well-characterized lipoproteins, but not a non-lipoprotein, was
      clearly shown to be aberrant in A909DeltaLgt. The mutant strain was shown to be
      more sensitive to oxidative stress in vitro although the molecular basis of this
      increased sensitivity was not apparent. The inactivation of Lgt also resulted in
      changes to the bacterial cell envelope, as demonstrated by reduced retention of
      both the group B carbohydrate and the polysaccharide capsule and a statistically
      significant reduction (P=0.0079) in A909DeltaLgt adherence to human endothelial
      cells of fetal origin. These data confirm that failure to process lipoproteins
      correctly has pleiotropic effects that may be of significance to S. agalactiae
      colonization and pathogenesis.

PMID- 19383709
TI  - Characterization of a novel air-liquid interface biofilm of Pseudomonas
      fluorescens SBW25.
AB  - Pseudomonads are able to form a variety of biofilms that colonize the air-liquid
      (A-L) interface of static liquid microcosms, and differ in matrix composition,
      strength, resilience and degrees of attachment to the microcosm walls. From
      Pseudomonas fluorescens SBW25, mutants have evolved during prolonged adaptation
      evolution experiments which produce robust biofilms of the physically cohesive
      class at the A-L interface, and which have been well characterized. In this study
      we describe a novel A-L interface biofilm produced by SBW25 that is categorized
      as a viscous mass (VM)-class biofilm. Several metals were found to induce this
      biofilm in static King's B microcosms, including copper, iron, lead and
      manganese, and we have used iron to allow further examination of this structure.
      Iron was demonstrated to induce SBW25 to express cellulose, which provided the
      matrix of the biofilm, a weak structure that was readily destroyed by physical
      disturbance. This was confirmed in situ by a low (0.023-0.047 g) maximum
      deformation mass and relatively poor attachment as measured by crystal violet
      staining. Biofilm strength increased with increasing iron concentration, in
      contrast to attachment levels, which decreased with increasing iron. Furthermore,
      iron added to mature biofilms significantly increased strength, suggesting that
      iron also promotes interactions between cellulose fibres that increase matrix
      interconnectivity. Whilst weak attachment is important in maintaining the biofilm
      at the A-L interface, surface-interaction effects involving cellulose, which
      reduced surface tension by approximately 3.8 mN m(-1), may also contribute
      towards this localization. The fragility and viscoelastic nature of the biofilm
      were confirmed by controlled-stress amplitude sweep tests to characterize
      critical rheological parameters, which included a shear modulus of 0.75 Pa, a
      zero shear viscosity of 0.24 Pa s(-1) and a flow point of 0.028 Pa. Growth and
      morphological data thus far support a non-specific metal-associated
      physiological, rather than mutational, origin for production of the SBW25 VM
      biofilm, which is an example of the versatility of bacteria to inhabit optimal
      niches within their environment.

PMID- 19383710
TI  - Strategies for acquiring the phospholipid metabolite inositol in pathogenic
      bacteria, fungi and protozoa: making it and taking it.
AB  - myo-Inositol (inositol) is an essential nutrient that is used for building
      phosphatidylinositol and its derivatives in eukaryotes and even in some
      eubacteria such as the mycobacteria. As a consequence, fungal, protozoan and
      mycobacterial pathogens must be able to acquire inositol in order to proliferate
      and cause infection in their hosts. There are two primary mechanisms for
      acquiring inositol. One is to synthesize inositol from glucose 6-phosphate using
      two sequentially acting enzymes: inositol-3-phosphate synthase (Ino1p) converts
      glucose 6-phosphate to inositol 3-phosphate, and then inositol monophosphatase
      (IMPase) dephosphorylates inositol 3-phosphate to generate inositol. The other
      mechanism is to import inositol from the environment via inositol transporters.
      Inositol is readily abundant in the bloodstream of mammalian hosts, providing a
      source from which many pathogens could potentially import inositol. However,
      despite this abundance of inositol in the host, some pathogens such as the
      bacterium Mycobacterium tuberculosis and the protist parasite Trypanosoma brucei
      must be able to make inositol de novo in order to cause disease (M. tuberculosis)
      or even grow (T. brucei). Other pathogens such as the fungus Candida albicans are
      equally adept at causing disease by importing inositol or by making it de novo.
      The role of inositol acquisition in the biology and pathogenesis of the parasite
      Leishmania and the fungus Cryptococcus are being explored as well. The specific
      strategies used by these pathogens to acquire inositol while in the host are
      discussed in relation to each pathogen's unique metabolic requirements.

PMID- 19383711
TI  - Gis1 is required for transcriptional reprogramming of carbon metabolism and the
      stress response during transition into stationary phase in yeast.
AB  - Transition from growth to the stationary phase in yeast is still poorly
      understood. Previously, we identified a group of yeast genes that are universally
      upregulated upon starvation for different macronutrients. Here, we demonstrate
      that the Gis1 transcription factor and the Rim15 kinase are responsible for the
      upregulation of many of these genes. In chemostat cultures, gis1 or rim15 mutant
      cells are outcompeted by their wild-type parents under conditions resembling the
      later stages of diauxie (glucose-limiting) and post-diauxie (ethanol as a carbon
      source). Whilst Gis1p and Rim15p have distinct functions in gene repression, the
      growth defects of gis1 or rim15 deletants can be accounted for by the overlapping
      functions of their protein products in promoting the expression of genes involved
      in glutamate biosynthesis, the glyoxylate cycle, the pentose phosphate pathway
      and the stress response. Further, we show that the sets of GIS1- and RIM15
      dependent genes and the degree of their regulation change in response to the
      identity of the carbon source, suggesting the likely dynamics of gene regulation
      exerted by Rim15p and Gis1p during different phases of the transition into
      stationary phase. In particular, Rim15p is required for the expression of genes
      involved in gluconeogenesis/glycolysis and glycerol biosynthesis only when
      ethanol is used as the carbon source. In agreement with this, Rim15p is shown to
      act in parallel with Hog1p to defend cells against osmotic stress.

PMID- 19383712
TI  - Cellular chain formation in Escherichia coli biofilms.
AB  - In this study we report on a novel structural phenotype in Escherichia coli
      biofilms: cellular chain formation. Biofilm chaining in E. coli K-12 was found to
      occur primarily by clonal expansion, but was not due to filamentous growth.
      Rather, chain formation was the result of intercellular interactions facilitated
      by antigen 43 (Ag43), a self-associating autotransporter (SAAT) protein, which
      has previously been implicated in auto-aggregation and biofilm formation.
      Immunofluorescence microscopy suggested that Ag43 was concentrated at or near the
      cell poles, although when the antigen was highly overexpressed, a much more
      uniform distribution was seen. Immunofluorescence microscopy also indicated that
      other parameters, including dimensional constraints (flow, growth alongside a
      surface), may also affect the final biofilm architecture. Moreover, chain
      formation was affected by other surface structures; type I fimbriae expression
      significantly reduced cellular chain formation, presumably by steric hindrance.
      Cellular chain formation did not appear to be specific to E. coli K-12. Although
      many urinary tract infection (UTI) isolates were found to form rather
      homogeneous, flat biofilms, three isolates, including the prototypic asymptomatic
      bacteriuria strain, 83972, formed highly elaborate cellular chains during biofilm
      growth in human urine. Combined, these results illustrate the diversity of
      biofilm architectures that can be observed even within a single microbial
      species.

PMID- 19383713
TI  - hetR and patS, two genes necessary for heterocyst pattern formation, are
      widespread in filamentous nonheterocyst-forming cyanobacteria.
AB  - Heterocysts, cells specialized in N(2) fixation in cyanobacteria, appeared at
      near to 2.1 Ga. They constitute one of the oldest forms of differentiated cells
      in evolution, and are thus an interesting model for studies on evolutionary
      developmental biology. How heterocysts arose during evolution remains unknown. In
      Anabaena PCC 7120, heterocyst development requires, among other genes, hetR for
      the initiation of heterocyst differentiation, and patS, encoding a diffusible
      inhibitor of heterocyst formation. In this study, we report that both hetR and
      patS are widespread among filamentous cyanobacteria that do not form heterocysts
      or fix N(2). hetR and patS are found in proximity on the chromosome in several
      cases, such as Arthrospira platensis, in which the level of HetR increased
      following nitrogen deprivation. The hetR gene of A. platensis could complement a
      hetR mutant of Anabaena PCC 7120, and patS of A. platensis could suppress
      heterocyst differentiation in Anabaena PCC 7120. Thus, key regulatory genes,
      including hetR and patS, involved in heterocyst development may have evolved
      before heterocysts appeared, suggesting that their function was not limited to
      heterocyst differentiation.

PMID- 19383714
TI  - Impairment of D-alanine biosynthesis in Mycobacterium smegmatis determines
      decreased intracellular survival in human macrophages.
AB  - d-Alanine is a structural component of mycobacterial peptidoglycan. The primary
      route of d-alanine biosynthesis in eubacteria is the enantiomeric conversion from
      l-alanine, a reaction catalysed by d-alanine racemase (Alr). Mycobacterium
      smegmatis alr insertion mutants are not dependent on d-alanine for growth and
      display a metabolic pattern consistent with an alternative pathway for d-alanine
      biosynthesis. In this study, we demonstrate that the M. smegmatis alr insertion
      mutant TAM23 can synthesize d-alanine at lower levels than the parental strain.
      The insertional inactivation of the alr gene also decreases the intracellular
      survival of mutant strains within primary human monocyte-derived macrophages. By
      complementation studies, we confirmed that the impairment of alr gene function is
      responsible for this reduced survival. Inhibition of superoxide anion and nitric
      oxide formation in macrophages suppresses the differential survival. In contrast,
      for bacteria grown in broth, both strains had approximately the same
      susceptibility to hydrogen peroxide, acidified sodium nitrite, low pH and
      polymyxin B. In contrast, TAM23 exhibited increased resistance to lysozyme. d
      Alanine supplementation considerably increased TAM23 viability in nutritionally
      deficient media and within macrophages. These results suggest that nutrient
      deprivation in phagocytic cells combined with killing mediated by reactive
      intermediates underlies the decreased survival of alr mutants. This knowledge may
      be valuable in the construction of mycobacterial auxotrophic vaccine candidates.

PMID- 19383715
TI  - Revealing the bovine embryo transcript profiles during early in vivo embryonic
      development.
AB  - Gene expression profiling is proving to be a powerful approach for the
      identification of molecular mechanisms underlying complex cellular functions such
      as the dynamic early embryonic development. The objective of this study was to
      perform a transcript abundance profiling analysis of bovine early embryonic
      development in vivo using a bovine developmental array. The molecular description
      of the first week of life at the mRNA level is particularly challenging when
      considering the important fluctuations in RNA content that occur between
      developmental stages. Accounting for the different intrinsic RNA content between
      developmental stages was achieved by restricting the reaction time during the
      global amplification steps and by using spiked controls and reference samples.
      Analysis based on intensity values revealed that most of the transcripts on the
      array were present at some point during in vivo bovine early embryonic
      development, while the varying number of genes detected in each developmental
      stage confirmed the dynamic profile of gene expression occurring during embryonic
      development. Pair-wise comparison of gene expression showed a marked difference
      between oocytes and blastocysts profiles, and principal component analysis
      revealed that the majority of the transcripts could be regrouped into three main
      clusters representing distinct RNA abundance profiles. Overall, these data
      provide a detailed temporal profile of the abundance of mRNAs revealing the
      richness of signaling processes in early mammalian development. Results presented
      here provide better knowledge of bovine in vivo embryonic development and
      contribute to the progression of our current knowledge regarding the first week
      of life in mammals.

PMID- 19383716
TI  - Pseudoinnovation: the development and spread of healthcare quality improvement
      methodologies.
AB  - BACKGROUND: Over the last two decades, we have seen the successive rise and fall
      of a number of concepts, ideas or methods in healthcare quality improvement (QI).
      Paradoxically, the content of many of these QI methodologies is very similar,
      though their presentation often seeks to differentiate or distinguish them.
      METHODS: This paper sets out to explore the processes by which new QI
      methodologies are developed and disseminated and the impact this has on the
      effectiveness of QI programmes in healthcare organizations. It draws on both a
      bibliometric analysis of the QI literature over the period from 1988 to 2007 and
      a review of the literature on the effectiveness of QI programmes and their
      evaluation. RESULTS: The repeated presentation of an essentially similar set of
      QI ideas and methods under different names and terminologies is a process of
      'pseudoinnovation', which may be driven by both the incentives for QI methodology
      developers and the demands and expectations of those responsible for QI in
      healthcare organizations. We argue that this process has important disbenefits
      because QI programmes need sustained and long-term investment and support in
      order to bring about significant improvements. The repeated redesign of QI
      programmes may have damaged or limited their effectiveness in many healthcare
      organizations. CONCLUSIONS: A more sceptical and scientifically rigorous approach
      to the development, evaluation and dissemination of QI methodologies is needed,
      in which a combination of theoretical, empirical and experiential evidence is
      used to guide and plan their uptake. Our expectations of the evidence base for QI
      methodologies should be on a par with our expectations in relation to other forms
      of healthcare interventions.

PMID- 19383717
TI  - Participation of the lipoprotein receptor LRP1 in hypoxia-HSP90alpha autocrine
      signaling to promote keratinocyte migration.
AB  - Hypoxia is a microenvironmental stress in many pathological conditions, including
      wound healing and tumor invasion. Under hypoxia, the cells are forced to adapt
      alternative and self-supporting mechanisms. Understanding these mechanisms may
      lead to new insights into human disorders. We report here a novel autocrine
      signaling mechanism by which hypoxia promotes human keratinocyte (HK) migration.
      First, hypoxia triggers HKs to secrete heat shock protein 90-alpha (HSP90alpha)
      via a HIF1-dependent pathway. The secreted HSP90alpha in turn promotes migration,
      but not proliferation, of the cells. Disruption of the secretion or extracellular
      function of HSP90alpha blocked hypoxia-stimulated HK migration. The ubiquitously
      expressed surface receptor, LRP1 (LDL-receptor-related protein 1), mediates the
      HSP90alpha signaling. Inhibition of LRP1 binding to extracellular HSP90alpha by
      neutralizing antibodies or genetic silencing of the LRP1 receptor by RNAi
      completely nullified hypoxia-driven HK migration. Finally, re-introducing a RNAi
      resistant LRP1 cDNA into LRP1-downregulated HKs rescued the motogenic response of
      the cells to hypoxia. We propose that the hypoxia-HSP90alpha-LRP1 autocrine loop
      provides previously unrecognized therapeutic targets for human disorders such as
      chronic wounds and cancer invasion.

PMID- 19383718
TI  - A germline-specific isoform of eIF4E (IFE-1) is required for efficient
      translation of stored mRNAs and maturation of both oocytes and sperm.
AB  - Fertility and embryonic viability are measures of efficient germ cell growth and
      development. During oogenesis and spermatogenesis, new proteins are required for
      both mitotic expansion and differentiation. Qualitative and quantitative changes
      in protein synthesis occur by translational control of mRNAs, mediated in part by
      eIF4E, which binds the mRNAs 5' cap. IFE-1 is one of five eIF4E isoforms
      identified in C. elegans. IFE-1 is expressed primarily in the germ line and
      associates with P granules, large mRNPs that store mRNAs. We isolated a strain
      that lacks IFE-1 [ife-1(bn127)] and demonstrated that the translation of several
      maternal mRNAs (pos-1, pal-1, mex-1 and oma-1) was inefficient relative to that
      in wild-type worms. At 25 degrees C, ife-1(bn127) spermatocytes failed in
      cytokinesis, prematurely expressed the pro-apoptotic protein CED-4/Apaf-1, and
      accumulated as multinucleate cells unable to mature to spermatids. A modest
      defect in oocyte development was also observed. Oocytes progressed normally
      through mitosis and meiosis, but subsequent production of competent oocytes
      became limiting, even in the presence of wild-type sperm. Combined gametogenesis
      defects decreased worm fertility by 80% at 20 degrees C; ife-1 worms were
      completely sterile at 25 degrees C. Thus, IFE-1 plays independent roles in late
      oogenesis and spermatogenesis through selective translation of germline-specific
      mRNAs.

PMID- 19383720
TI  - Attenuation of Notch signalling by the Down-syndrome-associated kinase DYRK1A.
AB  - Notch signalling is used throughout the animal kingdom to spatially and
      temporally regulate cell fate, proliferation and differentiation. Its importance
      is reflected in the dramatic effects produced on both development and health by
      small variations in the strength of the Notch signal. The Down-syndrome
      associated kinase DYRK1A is coexpressed with Notch in various tissues during
      embryonic development. Here we show that DYRK1A moves to the nuclear
      transcription compartment where it interacts with the intracellular domain of
      Notch promoting its phosphorylation in the ankyrin domain and reducing its
      capacity to sustain transcription. DYRK1A attenuates Notch signalling in neural
      cells both in culture and in vivo, constituting a novel mechanism capable of
      modulating different developmental processes that can also contribute to the
      alterations observed during brain development in animal models of Down syndrome.

PMID- 19383721
TI  - RalA and the exocyst complex influence neuronal polarity through PAR-3 and aPKC.
AB  - Neuronal polarization requires localized cytoskeletal changes and polarized
      membrane traffic. Here, I report that the small GTPase RalA, previously shown to
      control neurite branching, also regulates neuronal polarity. RalA depletion, or
      ectopic expression of constitutively active RalA in cultured neurons inhibit axon
      formation. However, expression of a constitutively active RalA mutant that is
      unable to interact with the exocyst complex has no effect on neuronal
      polarization. Furthermore, depletion of the Sec6, Sec8 or Exo84 subunits of the
      exocyst complex also leads to unpolarized neurons. Early stages of neuronal
      polarization are accompanied by increasing levels of interaction of the exocyst
      complex with PAR-3 and atypical protein kinase C (aPKC), and by the RalA
      dependent association of the exocyst complex with PAR-3. Thus, neuronal
      polarization involves a RalA-regulated association between mediators of vesicle
      trafficking (exocyst complex) and cell polarity (PAR-3).

PMID- 19383719
TI  - Lamin B1 maintains the functional plasticity of nucleoli.
AB  - The dynamic ability of genomes to interact with discrete nuclear compartments
      appears to be essential for chromatin function. However, the extent to which
      structural nuclear proteins contribute to this level of organization is largely
      unresolved. To test the links between structure and function, we evaluated how
      nuclear lamins contribute to the organization of a major functional compartment,
      the nucleolus. HeLa cells with compromised expression of the genes encoding
      lamins were analyzed using high-resolution imaging and pull-down assays. When
      lamin B1 expression was depleted, inhibition of RNA synthesis correlated with
      complex structural changes within the nucleolar active centers until, eventually,
      the nucleoli were dispersed completely. With normal lamin expression, the
      nucleoli were highly plastic, with dramatic and freely reversible structural
      changes correlating with the demand for ribosome biogenesis. Preservation of the
      nucleolar compartment throughout these structural transitions is shown to be
      linked to lamin B1 expression, with the lamin B1 protein interacting with the
      major nucleolar protein nucleophosmin/B23.

PMID- 19383722
TI  - Dominant roles of the polybasic proline motif and copper in the PrP23-89-mediated
      stress protection response.
AB  - Beta-cleavage of the neurodegenerative disease-associated prion protein (PrP)
      protects cells from death induced by oxidative insults. The beta-cleavage event
      produces two fragments, designated N2 and C2. We investigated the role of the N2
      fragment (residues 23-89) in cellular stress response, determining mechanisms
      involved and regions important for this reaction. The N2 fragment differentially
      modulated the reactive oxygen species (ROS) response induced by serum
      deprivation, with amelioration when copper bound. Amino acid residues 23-50 alone
      mediated a ROS reduction response. PrP23-50 ROS reduction was not due to copper
      binding or direct antioxidant activity, but was instead mediated through
      proteoglycan binding partners localised in or interacting with cholesterol-rich
      membrane domains. Furthermore, mutational analyses of both PrP23-50 and N2 showed
      that their protective capacity requires the sterically constraining double
      proline motif within the N-terminal polybasic region. Our findings show that N2
      is a biologically active fragment that is able to modulate stress-induced
      intracellular ROS through interaction of its structurally defined N-terminal
      polybasic region with cell-surface proteoglycans.

PMID- 19383724
TI  - Claudin-10 exists in six alternatively spliced isoforms that exhibit distinct
      localization and function.
AB  - The tight junction protein claudin-10 is known to exist in two isoforms,
      resulting from two alternative exons, 1a and 1b (Cldn10a, Cldn10b). Here, we
      identified and characterized another four claudin-10 splice variants in mouse and
      human. One (Cldn10a_v1) results from an alternative splice donor site, causing a
      deletion of the last 57 nucleotides of exon 1a. For each of these three variants
      one further splice variant was identified (Cldn10a_v2, Cldn10a_v3, Cldn10b_v1),
      lacking exon 4. When transfected into MDCK cells, Cldn10a, Cldn10a_v1 and Cldn10b
      were inserted into the tight junction, whereas isoforms of splice variants
      lacking exon 4 were retained in the endoplasmic reticulum. Cldn10a transfection
      into MDCK cells confirmed the previously described increase in paracellular anion
      permeability. Cldn10a_v1 transfection had no direct effect, but modulated Cldn10a
      induced organic anion permeability. At variance with previous reports in MDCK-II
      cells, transfection of high-resistance MDCK-C7 cells with Cldn10b dramatically
      decreased transepithelial resistance, increased cation permeability, and changed
      monovalent cation selectivity from Eisenman sequence IV to X, indicating the
      presence of a high field-strength binding site that almost completely removes the
      hydration shell of the permeating cations. The extent of all these effects
      strongly depended on the endogenous claudins of the transfected cells.

PMID- 19383723
TI  - Multicopy suppressor analysis of thermosensitive YIP1 alleles implicates GOT1 in
      transport from the ER.
AB  - Yip1p belongs to a conserved family of membrane-spanning proteins that are
      involved in intracellular trafficking. Studies have shown that Yip1p forms a
      heteromeric integral membrane complex, is required for biogenesis of ER-derived
      COPII vesicles, and can interact with Rab GTPases. However, the role of the Yip1
      complex in vesicle budding is not well understood. To gain further insight, we
      isolated multicopy suppressors of the thermosensitive yip1-2 allele. This screen
      identified GOT1, FYV8 and TSC3 as novel high-copy suppressors. The strongest
      suppressor, GOT1, also displayed moderate suppressor activity toward temperature
      sensitive mutations in the SEC23 and SEC31 genes, which encode subunits of the
      COPII coat. Further characterization of Got1p revealed that this protein was
      efficiently packaged into COPII vesicles and cycled rapidly between the ER and
      Golgi compartments. Based on the findings we propose that Got1p has an unexpected
      role in vesicle formation from the ER by influencing membrane properties.

PMID- 19383725
TI  - Endocytosis of MHC molecules by distinct membrane rafts.
AB  - In B-lymphocytes, endocytosis of MHC I and MHC II molecules is important for the
      cross-priming and presentation of labile antigens, respectively. Here, we report
      that MHC I and MHC II were internalized by separate endocytic carriers that
      lacked transferrin receptor. Cholera toxin B was co-internalized with MHC II, but
      not with MHC I, suggesting that the CLIC/GEEC pathway is involved in the uptake
      of MHC II. Endocytosis of MHC I and MHC II was inhibited by filipin, but only MHC
      II showed a strong preference for a membrane raft environment in a co-clustering
      analysis with G(M)1. By using a novel method for the extraction of detergent
      resistant membranes (DRMs), we observed that MHC I and MHC II associate with two
      distinct types of DRMs. These differ in density, protein content, lipid
      composition, and ultrastructure. The results of cell surface biotinylation and
      subsequent DRM isolation show that precursors for both DRMs coexist in the plasma
      membrane. Moreover, clustering of MHC proteins at the cell surface resulted in
      shifts of the respective DRMs, revealing proximity-induced changes in the
      membrane environment. Our results suggest that the preference of MHC I and MHC II
      for distinct membrane rafts directs them to different cellular entry points.

PMID- 19383726
TI  - Molecular phylogenetics and morphological reappraisal of the Platanthera clade
      (Orchidaceae: Orchidinae) prompts expansion of the generic limits of Galearis and
      Platanthera.
AB  - BACKGROUND AND AIMS: The Platanthera clade dominates the North American orchid
      flora and is well represented in eastern Asia. It has also generated some classic
      studies of speciation in Platanthera sections Platanthera and Limnorchis.
      However, it has proved rich in taxonomic controversy and near-monotypic genera.
      The clade is reviewed via a new molecular phylogenetic analysis and those results
      are combined with brief reconsideration of morphology in the group, aiming to
      rationalize the species into a smaller number of larger monophyletic genera and
      sections. METHODS: Nuclear ribosomal internal transcribed spacer (ITS) sequences
      were obtained from 86 accessions of 35 named taxa, supplemented from GenBank with
      five accessions encompassing a further two named taxa. KEY RESULTS: Using
      Pseudorchis as outgroup, and scoring indels, the data matrix generated 30 most
      parsimonious trees that differed in the placement of two major groups plus two
      closely related species. Several other internal nodes also attracted only
      indifferent statistical support. Nonetheless, by combining implicit assessment of
      morphological divergence with explicit assessment of molecular divergence (when
      available), nine former genera can be rationalized into four revised genera by
      sinking the monotypic Amerorchis, together with Aceratorchis and Chondradenia
      (neither yet sequenced), into Galearis, and by amalgamating Piperia, Diphylax and
      the monotypic Tsaiorchis into the former Platanthera section Platanthera. After
      further species sampling, this section will require sub-division into at least
      three sections. The present nomenclatural adjustments prompt five new
      combinations. CONCLUSIONS: Resolution of major groups should facilitate future
      species-level research on the Platanthera clade. Recent evidence suggests that
      ITS sequence divergence characterizes most species other than the P. bifolia
      group. The floral differences that distinguished Piperia, Diphylax and Tsaiorchis
      from Platanthera, and Aceratorchis and Chondradenia from Galearis, reflect
      various forms of heterochrony (notably paedomorphosis); this affected both the
      perianth and the gynostemium, and may have proved adaptive in montane habitats.
      Floral reduction was combined with lateral expansion of the root tubers in
      Piperia and Diphylax (including Tsaiorchis), whereas root tubers were minimized
      in the putative (but currently poorly supported) Neolindleya-Galearis clade.
      Allopolyploidy and/or autogamy strongly influenced speciation in Platanthera
      section Limnorchis and perhaps also Neolindleya. Reproductive biology remains an
      important driver of evolution in the clade, though plant-pollinator specificity
      and distinctness of the species boundaries have often been exaggerated.

PMID- 19383727
TI  - Analysis of mutational resistance to trimethoprim in Staphylococcus aureus by
      genetic and structural modelling techniques.
AB  - OBJECTIVES: This study sought to expand knowledge on the molecular mechanisms of
      mutational resistance to trimethoprim in Staphylococcus aureus, and the fitness
      costs associated with resistance. METHODS: Spontaneous trimethoprim-resistant
      mutants of S. aureus SH1000 were recovered in vitro, resistance genotypes
      characterized by DNA sequencing of the gene encoding the drug target (dfrA) and
      the fitness of mutants determined by pair-wise growth competition assays with
      SH1000. Novel resistance genotypes were confirmed by ectopic expression of dfrA
      alleles in a trimethoprim-sensitive S. aureus strain. Molecular models of S.
      aureus dihydrofolate reductase (DHFR) were constructed to explore the structural
      basis of trimethoprim resistance, and to rationalize the observed in vitro
      fitness of trimethoprim-resistant mutants. RESULTS: In addition to known amino
      acid substitutions in DHFR mediating trimethoprim resistance (F(99)Y and
      H(150)R), two novel resistance polymorphisms (L(41)F and F(99)S) were identified
      among the trimethoprim-resistant mutants selected in vitro. Molecular modelling
      of mutated DHFR enzymes provided insight into the structural basis of
      trimethoprim resistance. Calculated binding energies of the substrate
      (dihydrofolate) for the mutant and wild-type enzymes were similar, consistent
      with apparent lack of fitness costs for the resistance mutations in vitro.
      CONCLUSIONS: Reduced susceptibility to trimethoprim of DHFR enzymes carrying
      substitutions L(41)F, F(99)S, F(99)Y and H(150)R appears to result from
      structural changes that reduce trimethoprim binding to the enzyme. However, the
      mutations conferring trimethoprim resistance are not associated with fitness
      costs in vitro, suggesting that the survival of trimethoprim-resistant strains
      emerging in the clinic may not be subject to a fitness disadvantage.

PMID- 19383728
TI  - European Surveillance of Antimicrobial Consumption (ESAC): outpatient parenteral
      antibiotic treatment in Europe.
AB  - OBJECTIVES: To assess the proportion of parenteral treatment of the total
      outpatient antibiotic use in Europe, and to identify the antibiotic groups and
      individual antibiotics most commonly administered in this way. METHODS: Within
      the European Surveillance of Antimicrobial Consumption (ESAC; www.esac.ua.ac.be),
      using the anatomic therapeutic chemical (ATC) and defined daily dose (DDD)
      classification, data on outpatient use of antibacterials for systemic use (ATC
      J01), aggregated at the level of the active substance and expressed in DDD per
      1000 inhabitants per day (DID; WHO version 2007), were extracted for 2006 by
      route of administration and by country. Parenteral use was expressed as a
      percentage of the total outpatient use in DID. RESULTS: In 20 European countries,
      the total outpatient antibiotic use ranged from 27.91 DID in France to 9.58 DID
      in Russia. The proportion of outpatient parenteral antibiotic treatment ranged
      from 6.75% in Russia to 0.001% in Iceland. The three most commonly used
      antibiotic groups for parenteral treatment in Europe were the cephalosporins
      (J01D; 44.58%), the aminoglycosides (J01G; 25.27%) and the penicillins (J01C;
      17.78%). Four antibiotics [gentamicin (J01GB03) 18.53%; ceftriaxone (J01DD04)
      17.85%; cefazolin (J01DB04) 13.16%; and lincomycin (J01FF02) 5.47%] represented
      more than half of the use. CONCLUSIONS: In all 20 European countries studied
      together, 2.04% of outpatient antibiotics were used for parenteral treatment.
      However, as for the total outpatient antibiotic use and the use of different
      antibiotic groups and antibiotics, there is a striking variation in the
      proportions of parenteral antibiotic use in Europe. More in-depth data on
      outpatient antibiotic use are needed to explain this variation.

PMID- 19383729
TI  - Improving relatives' consent to organ donation.

PMID- 19383730
TI  - Modifiable factors influencing relatives' decision to offer organ donation:
      systematic review.
AB  - OBJECTIVE: To identify modifiable factors that influence relatives' decision to
      allow organ donation. DESIGN: Systematic review. DATA SOURCES: Medline, Embase,
      and CINAHL, without language restriction, searched to April 2008. Review methods
      Three authors independently assessed the eligibility of the identified studies.
      We excluded studies that examined only factors affecting consent that could not
      be altered, such as donor ethnicity. We extracted quantitative results to an
      electronic database. For data synthesis, we summarised the results of studies
      comparing similar themes. RESULTS: We included 20 observational studies and
      audits. There were no randomised controlled trials. The main factors associated
      with reduced rates of refusal were the provision of adequate information on the
      process of organ donation and its benefits; high quality of care of potential
      organ donors; ensuring relatives had a clear understanding of brain stem death;
      separating the request for organ donation from notification that the patient had
      died; making the request in a private setting; and using trained and experienced
      individuals to make the request. CONCLUSIONS: Limited evidence suggests that
      there are modifiable factors in the process of requests for organ donation, in
      particular the skills of the individual making the request and the timing of this
      conversation, that might have a significant impact on rates of consent. Targeting
      these factors might have a greater and more immediate effect on the number of
      organs for donation than legislative or other long term strategies.

PMID- 19383731
TI  - Fish consumption, marine omega-3 fatty acids, and incidence of heart failure: a
      population-based prospective study of middle-aged and elderly men.
AB  - AIMS: Fatty fish and marine omega-3 fatty acids were associated with lower rates
      of heart failure (HF) among US elderly, but this has not been confirmed in
      broader age ranges or other populations where source and type of fish may differ.
      We therefore conducted a population-based, prospective study of 39 367 middle
      aged and older Swedish men. METHODS AND RESULTS: Diet was measured using food
      frequency questionnaires. Men were followed for HF through Swedish inpatient and
      cause-of-death registers from 1 January 1998 to 31 December 2004. We used
      proportional hazards models adjusted for age and other covariates to estimate
      hazard ratios (HR). Compared with no consumption, men who ate fatty fish once per
      week had an HR of 0.88 (95% CI 0.68-1.13). Hazard ratios for consumption two
      times per week and > or =3 times per week were 0.99 and 0.97, respectively.
      Hazard ratios across quintiles of marine omega-3 were 1, 0.94 (95% CI 0.74-1.20),
      0.67 (95% CI 0.50-0.90), 0.89 (95% CI 0.68-1.16), 1.00 (95% CI 0.77-1.29).
      CONCLUSION: In this population, moderate intake of fatty fish and marine omega-3
      fatty acids was associated with lower rates of HF, though the association for
      fish intake was not statistically significant; higher intake was not associated
      with additional benefit.

PMID- 19383732
TI  - Prevalence, incidence, and prognostic value of anaemia in patients after an acute
      myocardial infarction: data from the OPTIMAAL trial.
AB  - AIMS: The prevalence, incidence, and prognostic value of anaemia in patients with
      an acute myocardial infarction (AMI) complicated by heart failure is unclear.
      METHODS AND RESULTS: We analysed the relationship between haemoglobin (Hb) and
      outcome in 5010 patients with AMI complicated by heart failure in the OPTIMAAL
      study. In 3921 patients, follow-up Hb levels were available at 365 (+/-90) days.
      In a subgroup of 224 patients, iron-related haematinics were assessed at baseline
      and during follow-up. At baseline, mean Hb was 12.6 +/- 1.3 g/dL in women and
      13.7 +/- 1.4 g/dL in men. Hb < 11.5 g/dL was found in 9.3% of patients (women:
      18.2%, men: 5.8%). Lower haemoglobin at baseline was clearly associated with
      female gender and the presence of diabetes, higher age and Killip class, lower
      body mass index, systolic blood pressure, total cholesterol, and the absence of
      current smoking (all P < 0.05). Higher Hb [per one standard deviation (SD)]
      related to lower mortality [adjusted hazard ratios (HR) 0.88; 95% confidence
      interval (CI) 0.83-0.93], CHF hospitalizations [HR 0.85 (0.77-0.93)], and all
      cause hospitalizations [HR 0.96 (0.92-0.99), all P < 0.05]. In patients without
      anaemia at baseline, the anaemia incidence after 1 year of follow-up was 10.1% in
      women and 10.0% in men. Of patients with anaemia at baseline, 65% did not have
      anaemia at 12 months and 46% did not have anaemia at any time during follow-up
      (median 3.0 years, inter-quartile range, Q1-Q3 = 2.7-3.3 years). At 12 months, an
      increase in Hb (per SD) was related to lower mortality [HR 0.73 (0.63-0.85; P <
      0.0001)] independent of baseline Hb and other clinical characteristics.
      CONCLUSION: In patients with complicated AMIs, anaemia on admission and/or
      reductions in haemoglobin during follow-up are independent risk factors for
      mortality and hospitalization. Studies are warranted to determine whether
      correcting anaemia after a complicated AMI improves outcome.

PMID- 19383733
TI  - Angiotensin-converting enzyme inhibitors in patients with vascular disease.

PMID- 19383734
TI  - Sirolimus as primary immunosuppression is associated with improved coronary
      vasomotor function compared with calcineurin inhibitors in stable cardiac
      transplant recipients.
AB  - AIMS: The aim of this study was to evaluate coronary vasomotor function in
      cardiac transplant recipients maintained on sirolimus (SRL)- or cyclosporin (CyA)
      based immunosuppression. METHODS AND RESULTS: Endothelium-independent response to
      intracoronary nitroglycerin and adenosine and endothelium-dependent response to
      intracoronary acetylcholine (Ach) were assessed in 15 SRL- and 21 CyA- treated
      subjects with angiographically normal coronary arteries. Baseline mean blood
      pressure was lower in the SRL group (85.6 +/- 10.3 vs. 105.2 +/- 8.7 mmHg, P =
      0.002). There was no difference between the groups in coronary flow reserve after
      adenosine administration in multivariable analysis (P = 0.34). Nitroglycerin
      administration resulted in increase in coronary artery diameter in the SRL
      compared with the CyA groups (2.79 +/- 0.54 vs. 2.57 +/- 0.61, P = 0.0036). In 13
      SRL-treated subjects without evidence of cardiac allograft vasculopathy (CAV),
      Ach administration resulted in less epicardial vasoconstriction compared with CyA
      treated subjects (2.7 +/- 17.7 vs. -15.6 +/- 17.2%, P = 0.005). Two SRL-treated
      subjects with three-dimensional intravascular ultrasound evidence of CAV
      developed coronary spasm in response to Ach 10(-4). Microvascular endothelial
      function did not differ between the groups. CONCLUSION: Sirolimus
      immunosuppression is associated with less pronounced coronary epicardial
      endothelial dysfunction compared with CyA immunosuppression. Improvement of
      coronary vasomotor function with SRL may be an important mechanism for the
      prevention of CAV.

PMID- 19383735
TI  - Pre-intervention eosinophil cationic protein serum levels predict clinical
      outcomes following implantation of drug-eluting stents.
AB  - AIMS: Eosinophils have been identified in post-mortem studies as important
      players of both restenosis and thrombosis after drug-eluting stent (DES)
      implantation. We aimed at assessing the association between baseline levels of
      eosinophil cationic protein (ECP), a marker of eosinophil activation, and
      recurrence of clinical events in a consecutive series of patients who underwent
      DES implantation. METHODS AND RESULTS: Two hundred patients (age 63 +/- 10.4,
      males 75%) undergoing implantation of first-generation DES (Taxus or Cypher
      stents) were enrolled. We measured serum levels of ECP and total IgE by enzyme
      linked immunosorbent assay and of C-reactive protein by high-sensitivity
      nephelometry prior to percutaneous coronary intervention. A clinical follow-up
      was planned 18 months after discharge. Major adverse cardiac events (MACEs), such
      as cardiac death, recurrent myocardial infarction, or clinically driven target
      lesion revascularization, were the endpoint of the study. Twenty-two patients
      (11%) had MACEs and showed higher serum levels of ECP compared with those without
      MACEs [30.5 (14.4-50) vs. 12.2 (4.4-31) microg/L, P = 0.004]. At simple Cox
      regression analysis, serum levels of ECP were a significant predictor of MACEs
      (hazard ratio 1.016, 95% confidence interval 1.003-1.03, P = 0.018). CONCLUSION:
      This study shows for the first time an association between baseline ECP levels
      and the occurrence of MACEs in patients undergoing implantation of DES. Further
      studies are warranted to establish whether in this setting ECP is a risk marker
      or plays a contributory pathogenetic role.

PMID- 19383736
TI  - Lipid-rich plaque and myocardial perfusion after successful stenting in patients
      with non-ST-segment elevation acute coronary syndrome: an optical coherence
      tomography study.
AB  - AIMS: Although some recent guidelines recommend an early invasive strategy for
      non-ST-segment elevation acute coronary syndrome (NSTEACS), several studies have
      failed to identify any benefit for very early intervention for NSTEACS. The no
      reflow phenomenon may inhibit the expected benefit from very early recanalization
      for NSTEACS subjects. The aim of this study was to investigate whether optical
      coherence tomography (OCT) could predict no-reflow in patients with NSTEACS.
      METHODS AND RESULTS: This study comprised 83 consecutive patients with NSTEACS
      who underwent OCT and successful emergent primary stenting. On the basis of post
      stent TIMI flow, patients were divided into two groups: no-reflow group (n = 14)
      and reflow group (n = 69). Thin-cap fibroatheroma (TCFA) was defined as a plaque
      presenting lipid content for >90 degrees , and with thinnest part of the fibrous
      cap measuring <70 microm. Thin-cap fibroatheroma were more frequently observed in
      the no-reflow group than in the reflow group (50% vs. 16%, P = 0.005). The
      frequency of the no-reflow phenomenon increases according to the size of the
      lipid arc in the culprit plaque. Final TIMI blush grade also deteriorated
      according to the increase in the lipid arc. A multivariable logistic regression
      model revealed that lipid arc alone was an independent predictor of no-reflow
      (odds ratio 1.018; CI 1.004-1.033; P = 0.01). CONCLUSION: Optical coherence
      tomography can predict no-reflow after percutaneous coronary intervention (PCI)
      in NSTEACS. The lipid contents of a culprit plaque may play a key role in damage
      to the microcirculation after PCI for NSTEACS. From our results, it is found that
      OCT is useful tool for stratifying risk for PCI for NSTEACS.

PMID- 19383737
TI  - Atrial fibrillation and heart rate independently correlate to microalbuminuria in
      hypertensive patients.
AB  - AIMS: To investigate the relationship between microalbuminuria (MAU) and atrial
      fibrillation (AF) and to further evaluate whether the heart rate dependency of
      MAU in patients without AF is maintained in patients with a history of AF.
      METHODS AND RESULTS: The International Survey Evaluating Microalbuminuria
      Routinely by Cardiologists in patients with Hypertension (I-SEARCH) included
      18,900 patients without and 1705 patients with a history of AF suffering from
      hypertension and other risk factors for cardiovascular disease in 26 countries
      worldwide from September 2005 to March 2006. Heart rate, blood pressure, urinary
      albumin excretion, and an estimated glomerular filtration rate were determined
      among other parameters. The prevalence of MAU was higher at higher heart rate in
      both patients with and without a history of AF. Prevalence of MAU was about 10%
      higher in patients with a history of AF (P < 0.001). Male gender, the presence of
      diabetes mellitus, a higher heart rate, and a higher diastolic blood pressure
      were independently associated with increased odds for MAU in patients without and
      with a history of AF. CONCLUSION: The prevalence of MAU in hypertensive patients
      with cardiovascular risk factors is related to heart rate and significantly
      higher in patients with a history of AF.

PMID- 19383738
TI  - Care of refused asylum seekers. Bad news for everyone.

PMID- 19383739
TI  - Health checks every five years. Ankle brachial pressure index?

PMID- 19383741
TI  - Neurogenic bladder dysfunction. Bladder stimulation for neurogenic bladder.

PMID- 19383740
TI  - Primary medical care market. Destabilisation of primary care with equitable
      access.

PMID- 19383742
TI  - Studies on Hysteria. The dark side of Freud's legacy.

PMID- 19383743
TI  - Death certification. Investigation of death is set to improve at last.

PMID- 19383744
TI  - Death certification. Better system in Scotland.

PMID- 19383745
TI  - Competing interests et al. Stealth advertising and academic stalking.

PMID- 19383746
TI  - Competing interests et al. JAMA's rule needs time limit.

PMID- 19383748
TI  - Should "body MOTs" and DNA profiling be regulated?

PMID- 19383749
TI  - Three elderly patients died from inappropriate drugs, inquest finds.

PMID- 19383750
TI  - Doctors as leaders.

PMID- 19383751
TI  - Does the FDA have the authority to trump the Declaration of Helsinki?

PMID- 19383752
TI  - This House believes doctors are neglecting their duty to lead health service
      change: Seconder.

PMID- 19383753
TI  - This house believes doctors are neglecting their duty to lead health service
      changes: Second opposer.

PMID- 19383754
TI  - This house believes doctors are neglecting their duty to lead health service
      change: Opposer.

PMID- 19383755
TI  - This house believes doctors are neglecting their duty to lead health service
      change: Proposer.

PMID- 19383756
TI  - Out of Hours. Fighting a lost cause?

PMID- 19383757
TI  - Patent pools: an idea whose time has come.

PMID- 19383759
TI  - West Africa has worst meningitis epidemic for 10 years.

PMID- 19383760
TI  - Management of lateral hip pain.

PMID- 19383761
TI  - Knotting of nasogastric tube around a nasotracheal tube: An unusual cause of
      hypercapnia in a 3-month-old infant.
AB  - A 3-month-old boy was admitted to the intensive care unit because of septic
      shock; he required immediate intubation and placement of a nasogastric tube. A
      confirmatory chest radiograph showed that the nasogastric tube was looping in the
      hypopharynx and needed to be repositioned. During removal of the nasogastric
      tube, the infant experienced hypercapnia and respiratory distress. These
      complications were due to looping and knotting of the nasogastric tube around the
      nasotracheal tube.

PMID- 19383762
TI  - Current practice in airway management: A descriptive evaluation.
AB  - BACKGROUND: Ventilator-associated pneumonia, a common complication of mechanical
      ventilation, could be reduced if health care workers implemented evidence-based
      practices that decrease the risk for this complication. OBJECTIVES: To determine
      current practice and differences in practices between registered nurses and
      respiratory therapists in managing patients receiving mechanical ventilation.
      METHODS: A descriptive comparative design was used. A convenience sample of 41
      registered nurses and 25 respiratory therapists who manage critical care patients
      treated with mechanical ventilation at Sharp Grossmont Hospital, La Mesa,
      California, completed a survey on suctioning techniques and airway management
      practices. Descriptive and inferential statistics were used to analyze the data.
      RESULTS: Significant differences existed between nurses and respiratory
      therapists for hyperoxygenation before suctioning (P =.03). In the 2 groups,
      nurses used the ventilator for hyper-oxygenation more often, and respiratory
      therapists used a bag-valve device more often (P =.03). Respiratory therapists
      instilled saline (P <.001) and rinsed the closed system with saline after
      suctioning (P =.003) more often than nurses did. Nurses suctioned oral secretions
      (P <.001) and the nose of orally intubated patients (P =.01), brushed patients'
      teeth with a toothbrush (P<.001), and used oral swabs to clean the mouth (P
      <.001) more frequently than respiratory therapists did. CONCLUSION: Nurses and
      respiratory therapists differed significantly in the management of patients
      receiving mechanical ventilation. To reduce the risk of ventilator-associated
      pneumonia, both nurses and respiratory therapists must be consistent in using
      best practices when managing patients treated with mechanical ventilation.

PMID- 19383763
TI  - Microbial community profiling for human microbiome projects: Tools, techniques,
      and challenges.
AB  - High-throughput sequencing studies and new software tools are revolutionizing
      microbial community analyses, yet the variety of experimental and computational
      methods can be daunting. In this review, we discuss some of the different
      approaches to community profiling, highlighting strengths and weaknesses of
      various experimental approaches, sequencing methodologies, and analytical
      methods. We also address one key question emerging from various Human Microbiome
      Projects: Is there a substantial core of abundant organisms or lineages that we
      all share? It appears that in some human body habitats, such as the hand and the
      gut, the diversity among individuals is so great that we can rule out the
      possibility that any species is at high abundance in all individuals: It is
      possible that the focus should instead be on higher-level taxa or on functional
      genes instead.

PMID- 19383764
TI  - Structure-activity relationships in Kluyveromyces lactis gamma-toxin, a eukaryal
      tRNA anticodon nuclease.
AB  - tRNA anticodon damage inflicted by secreted ribotoxins such as Kluyveromyces
      lactis gamma-toxin and bacterial colicins underlies a rudimentary innate immune
      system that distinguishes self from nonself species. The intracellular expression
      of gamma-toxin (a 232-amino acid polypeptide) arrests the growth of Saccharomyces
      cerevisiae by incising a single RNA phosphodiester 3' of the modified wobble base
      of tRNA(Glu). Fungal gamma-toxin bears no primary structure similarity to any
      known nuclease and has no plausible homologs in the protein database. To gain
      insight to gamma-toxin's mechanism, we tested the effects of alanine mutations at
      62 basic, acidic, and polar amino acids on ribotoxin activity in vivo. We thereby
      identified 22 essential residues, including 10 lysines, seven arginines, three
      glutamates, one cysteine, and one histidine (His209, the only histidine present
      in gamma-toxin). Structure-activity relations were gleaned from the effects of 44
      conservative substitutions. Recombinant tag-free gamma-toxin, a monomeric
      protein, incised an oligonucleotide corresponding to the anticodon stem-loop of
      tRNA(Glu) at a single phosphodiester 3' of the wobble uridine. The anticodon
      nuclease was metal independent. RNA cleavage was abolished by ribose 2'-H and 2'
      F modifications of the wobble uridine. Mutating His209 to alanine, glutamine, or
      asparagine abolished nuclease activity. We propose that gamma-toxin catalyzes an
      RNase A-like transesterification reaction that relies on His209 and a second
      nonhistidine side chain as general acid-base catalysts.

PMID- 19383765
TI  - Post-transcriptional control of DGCR8 expression by the Microprocessor.
AB  - The Microprocessor, comprising the RNase III Drosha and the double-stranded RNA
      binding protein DGCR8, is essential for microRNA (miRNA) biogenesis. In the miRNA
      processing pathway certain hairpin structures within primary miRNA (pri-miRNA)
      transcripts are specifically cleaved by the Microprocessor to release
      approximately 60-70-nucleotide precursor miRNA (pre-miRNA) intermediates.
      Although both Drosha and DGCR8 are required for Microprocessor activity, the
      mechanisms regulating the expression of these proteins are unknown. Here we
      report that the Microprocessor negatively regulates DGCR8 expression. Using in
      vitro reconstitution and in vivo studies, we demonstrate that a hairpin,
      localized in the 5' untranslated region (5'UTR) of DGCR8 mRNA, is cleaved by the
      Microprocessor. Accordingly, knockdown of Drosha leads to an increase in DGCR8
      mRNA and protein levels in cells. Furthermore, we found that the DGCR8 5'UTR
      confers Microprocessor-dependent repression of a luciferase reporter gene in
      vivo. Our results uncover a novel feedback loop that regulates DGCR8 levels.

PMID- 19383766
TI  - The fraction of RNA that folds into the correct branched secondary structure
      determines hepatitis delta virus type 3 RNA editing levels.
AB  - RNA editing by the host RNA adenosine deaminase ADAR1 at the amber/W site of
      hepatitis delta virus RNA plays a central role in the viral replication cycle by
      affecting the balance between viral RNA synthesis and packaging. Previously, we
      found that HDV genotype III (HDV-3) RNA can form two secondary structures
      following transcription: an unbranched rod structure, which is characteristic of
      HDV, and a metastable branched structure that serves as the substrate for
      editing. The unstable nature of the branched editing substrate structure raised
      the possibility that structural dynamics of the RNA following transcription could
      determine the rate at which editing occurs. Here, editing and its control are
      examined in two HDV-3 isolates, from Peru and Ecuador. Analysis of editing in
      vitro by ADAR1 indicated that the branched structure formed by RNA derived from
      the Peruvian isolate is edited more efficiently than that from the Ecuadorian
      isolate. In contrast, in the context of replication, Peruvian RNA is edited less
      efficiently than RNA containing Ecuadorian sequences. Computational analyses of
      RNA folding using the massively parallel genetic algorithm (MPGAfold) indicated
      that the Peruvian RNA is less likely to form the branched structure required for
      editing than the Ecuadorian isolate. This difference was confirmed by in vitro
      transcription of these RNAs. Overall, our data indicate that HDV-3 controls RNA
      editing levels via (1) the fraction of the RNA that folds, during transcription,
      into the metastable branched structure required for editing and (2) the
      efficiency with which ADAR1 edits this branched substrate RNA.

PMID- 19383767
TI  - SHQ1 is required prior to NAF1 for assembly of H/ACA small nucleolar and
      telomerase RNPs.
AB  - Assembly of H/ACA RNPs in yeast is aided by at least two accessory factors, Naf1p
      and Shq1p. Although the function of Naf1p and its human ortholog NAF1 has been
      delineated in detail, that of Shq1p and its putative human ortholog SHQ1 remains
      obscure. We demonstrate that SHQ1 indeed functions in the biogenesis of human
      H/ACA RNPs and we dissect its mechanism of action. Like NAF1, SHQ1 binds the
      major H/ACA core protein and pseudouridine synthase NAP57 (aka dyskerin) but
      precedes the assembly role of NAF1 at nascent H/ACA RNAs because the interaction
      of SHQ1 with NAP57 in vivo and in vitro precludes that of NAF1 and of the other
      H/ACA core proteins that are present at the sites of H/ACA RNA transcription. The
      N-terminal heat shock protein 20-like CS domain of SHQ1 is dispensable for NAP57
      binding. Consistent with its role as an assembly factor, SHQ1 localizes to the
      nucleoplasm and is excluded from nucleoli and Cajal bodies, the sites of mature
      H/ACA RNPs. In an in vitro assembly system of functional H/ACA RNPs that is
      dependent on NAF1, excess recombinant SHQ1 interferes with assembly. Importantly,
      knockdown of cellular SHQ1 prevents accumulation of a newly synthesized H/ACA
      reporter RNA and generally reduces the levels of endogenous H/ACA RNAs including
      telomerase RNA. In summary, the sequential action of SHQ1 and NAF1 is required
      for functional assembly of H/ACA RNPs in vivo and in vitro. This step-wise
      process could serve as an efficient means of quality control during H/ACA RNP
      assembly.

PMID- 19383768
TI  - The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound
      transcripts independently of Argonaute proteins.
AB  - Proteins of the GW182 family are essential components of the miRNA pathway in
      animal cells. Vertebrate genomes encode three GW182 paralogs (TNRC6A, TNRC6B, and
      TNRC6C), which may be functionally redundant. Here, we show that the N-terminal
      GW-repeat-containing regions of all three TNRC6s interact with the four human
      Argonaute proteins (AGO1-AGO4). We also show that TNRC6A, TNRC6B, and TNRC6C
      silence the expression of bound mRNAs. This activity is mediated by their C
      terminal silencing domains, and thus, is independent of the interaction with AGO1
      AGO4. Silencing by TNRC6A, TNRC6B, and TNRC6C is effected by changes in protein
      expression and mRNA stability that can, in part, be attributed to deadenylation.
      Our findings indicate that TNRC6A, TNRC6B, and TNRC6C are recruited to miRNA
      targets through an interaction between their N-terminal domain and an Argonaute
      protein; the TNRC6s then promote translational repression and/or degradation of
      miRNA targets through a C-terminal silencing domain.

PMID- 19383769
TI  - A C-terminal silencing domain in GW182 is essential for miRNA function.
AB  - Proteins of the GW182 family are essential for miRNA-mediated gene silencing in
      animal cells; they interact with Argonaute proteins (AGOs) and are required for
      both the translational repression and mRNA degradation mediated by miRNAs. To
      gain insight into the role of the GW182-AGO1 interaction in silencing, we
      generated protein mutants that do not interact and tested them in complementation
      assays. We show that silencing of miRNA targets requires the N-terminal domain of
      GW182, which interacts with AGO1 through multiple glycine-tryptophan (GW)
      repeats. Indeed, a GW182 mutant that does not interact with AGO1 cannot rescue
      silencing in cells depleted of endogenous GW182. Conversely, silencing is
      impaired by mutations in AGO1 that strongly reduce the interaction with GW182 but
      not with miRNAs. We further show that a GW182 mutant that does not localize to P
      bodies but interacts with AGO1 rescues silencing in GW182-depleted cells, even
      though in these cells, AGO1 also fails to localize to P-bodies. Finally, we show
      that in addition to the N-terminal AGO1-binding domain, the middle and C-terminal
      regions of GW182 (referred to as the bipartite silencing domain) are essential
      for silencing. Together our results indicate that miRNA silencing in animal cells
      is mediated by AGO1 in complex with GW182, and that P-body localization is not
      required for silencing.

PMID- 19383770
TI  - The yfiC gene of E. coli encodes an adenine-N6 methyltransferase that
      specifically modifies A37 of tRNA1Val(cmo5UAC).
AB  - Transfer RNA is highly modified. Nucleotide 37 of the anticodon loop is
      represented by various modified nucleotides. In Escherichia coli, the valine
      specific tRNA (cmo(5)UAC) contains a unique modification, N(6)-methyladenosine,
      at position 37; however, the enzyme responsible for this modification is unknown.
      Here we demonstrate that the yfiC gene of E. coli encodes an enzyme responsible
      for the methylation of A37 in tRNA(1)(Val). Inactivation of yfiC gene abolishes
      m(6)A formation in tRNA(1)(Val), while expression of the yfiC gene from a plasmid
      restores the modification. Additionally, unmodified tRNA(1)(Val) can be
      methylated by recombinant YfiC protein in vitro. Although the methylation of
      m(6)A in tRNA(1)(Val) by YfiC has little influence on the cell growth under
      standard conditions, the yfiC gene confers a growth advantage under conditions of
      osmotic and oxidative stress.

PMID- 19383771
TI  - Postoperative myocardial damages after hip fracture repair are frequent and
      associated with a poor cardiac outcome: a three-hospital study.

PMID- 19383772
TI  - Self-poisoning in older adults: patterns of drug ingestion and clinical outcomes.
AB  - BACKGROUND AND AIMS: self-poisoning accounts for a substantial proportion of
      acute medical hospital presentations, but has been poorly characterised in older
      adults. This study sought to determine the agents ingested by older adults
      presenting to hospital after drug overdose, and to compare clinical outcomes to
      younger patients. METHODS: a retrospective observational study of patients
      admitted via the emergency department due to drug overdose between 2004 and 2007.
      RESULTS: during the study period, there were 8,059 admissions, including 4,632
      women (57.5%). This included a subgroup of 361 patients (4.5%) who were >60 years
      of age. This subgroup was more likely to require hospital stay >1 night, odds
      ratio (95% confidence interval) = 4.3 (3.6-5.5, P < 0.0001), transfer to a
      critical care area = 3.8 (1.1-13.0, P = 0.0340) and had higher mortality = 4.8
      (1.1-22.1, P = 0.0463). A higher proportion of older patients required transfer
      to a psychiatric unit (P < 0.0001) or to a general medical ward (P < 0.0001) than
      younger adults. CONCLUSIONS: older adults that presented to hospital after drug
      overdose had ingested different drugs than younger patients, possibly due to
      different prescribing patterns, and had a poorer outcome. The use of drugs
      associated with significant toxicity should be avoided in older patients at risk
      of self-harm.

PMID- 19383773
TI  - The course of delirium in acute stroke.
AB  - BACKGROUND AND PURPOSE: several studies have assessed delirium post-stroke but
      conflicting results have been obtained. Also, the natural history and outcome of
      delirium post-stroke need to be fully elucidated. METHODOLOGY: eligible stroke
      patients were assessed for delirium on admission and for four consecutive weeks
      using the Confusion Assessment Method (CAM). Risk factors for delirium were
      recorded. Our outcome measures were length of stay, inpatient mortality and
      discharge destination. RESULTS: of 110 eligible patients, 82 were recruited over
      7 months. Delirium was detected in 23 patients (28%); 21 of these were delirious
      on their first assessment. Sixty-nine per cent of patients who had four weekly
      assessments were delirious at 4 weeks. Multivariate logistic regression analysis
      was performed, and two models were identified. With unsafe swallow in the
      analysis, delirium was associated with an unsafe swallow on admission (OR 28.4,
      P<0.001), Barthel score < 10 (OR 32.1, P = 0.004) and poor vision pre-stroke (OR
      110.8, P = 0.01). With unsafe swallow removed from the analysis, delirium was
      associated with an admission C-reactive protein (CRP) > 5 mg/l (OR 10.2, P =
      0.009), Barthel score < 10 (OR 46.5, P = 0.001) and poor vision pre-stroke (OR
      85.2, P = 0.01). Delirious patients had a higher mortality (30.4% vs. 1.7%,
      P<0.001), longer length of stay (62.2 vs. 28.9 days, P<0.001) and increased risk
      of institutionalisation (43.7 vs. 5.2%, OR 14, P<0.001). CONCLUSIONS: delirium is
      common post-stroke. Most cases develop at stroke onset and remain delirious for
      an appreciable period. Delirium onset is associated with stroke severity (low
      admission Barthel), unsafe swallow on admission, poor vision pre-stroke and a
      raised admission CRP. Delirium is a marker of poor prognosis.

PMID- 19383774
TI  - A single nucleotide polymorphism on exon-4 of the gene encoding PPARdelta is
      associated with reduced height in adults and children.
AB  - CONTEXT: Peroxisome proliferator-activated receptor (PPAR)-delta is a nuclear
      transcription factor that plays a key role in many metabolic processes, including
      energy metabolism, and lipid and glucose metabolism. Candidate gene studies have
      identified a putative functional variant, rs2016520, in the gene encoding
      PPARdelta (PPARD), which is associated in some studies with metabolic traits. In
      addition, this single-nucleotide polymorphism was associated with adult height in
      several whole-genome scans, but this association did not achieve whole genome
      significance. OBJECTIVE: This study sought to determine whether PPARD variation
      influenced height. DESIGN: Haplotype tagging analysis across PPARD was performed
      in about 11,000 individuals from the Wellcome Trust U.K. Type 2 Diabetes Case
      Control Collection (Go-DARTS2). RESULTS: There was an association between
      rs2016520 and height in both patients with type 2 diabetes and controls without
      diabetes (combined P = 5 x 10(-5)). In a metaanalysis using published data from
      Caucasian cohorts totaling more than 38,000 participants, compelling evidence was
      found for this locus and its association with height (P = 10(-8)) with an overall
      effect size of about 0.5 cm per allele. A similar analysis in a group of 2700
      prepubescent children also displayed a similar effect size to that seen in the
      adults. CONCLUSION: PPARD variation is clearly associated with a phenotype of
      reduced stature in both adults and children. Because height is an important
      indicator of metabolic and nutritional status, this provides additional support
      for a key role for PPARdelta in critical metabolic functions. PPARdelta may
      affect height through a variety of mechanisms including altered metabolic
      efficiency or effects on osteoclast function.

PMID- 19383775
TI  - Hypoglycemia from IGF2 overexpression associated with activation of fetal
      promoters and loss of imprinting in a metastatic hemangiopericytoma.
AB  - CONTEXT: The mechanism of IGF2 overexpression in non-islet-cell tumor
      hypoglycemia is not understood. OBJECTIVE: We investigated the imprinting control
      and promoter usage for IGF2 expression to identify a mechanism for increased IGF
      II production in non-islet-cell tumor hypoglycemia. PATIENT AND METHODS: A
      patient with metastatic hemangiopericytoma was studied. Tissue from the original
      hemangiopericytoma, metastatic tumor, and uninvolved liver was analyzed for IGF
      II immunohistochemistry. IGF2, a paternally imprinted gene, shares a control
      region with maternally imprinted H19, a putative tumor suppressor. IGF-II and H19
      mRNA expression was compared in metastatic tumor and uninvolved liver by
      quantitative RT-PCR. Imprinting of IGF2/H19 genes and IGF2 promoter usage in
      metastatic tumor was investigated by RT-PCR and sequence analysis, and the
      methylation pattern in the IGF2/H19 imprinting control region was analyzed.
      RESULTS: IGF-II protein expression was increased in metastatic tumor vs.
      uninvolved liver and original tumor. In the metastatic tumor, IGF-II mRNA was
      increased 60-fold, but H19 mRNA was comparable to uninvolved liver; loss of
      imprinting of IGF2, but not H19, was identified; no major change in methylation
      of the IGF2/H19 imprinting control regions was observed; and transcripts from
      four different IGF2 promoters were detected, compared to two in uninvolved liver.
      CONCLUSIONS: IGF-2 overexpression, newly acquired in the metastatic tumor, was
      associated with loss of IGF2 gene imprinting and different promoter usage. The
      imprinting control mechanism governing the IGF2/H19 locus was intact, as
      evidenced by normal levels of H19, maintenance of H19 imprinting, and no major
      change in methylation of the imprinting control regions.

PMID- 19383777
TI  - The relationship between central adrenal insufficiency and sleep-related
      breathing disorders in children with Prader-Willi syndrome.
AB  - BACKGROUND: The annual death rate of patients with Prader-Willi syndrome (PWS) is
      high (3%). Many deaths of children are sudden and unexplained. Sleep apneas have
      been suggested to play a role in sudden deaths. Recently, we discovered that 60%
      of patients with PWS suffer from central adrenal insufficiency (CAI) during
      stress. OBJECTIVE: The aim was to study the relationship between CAI and sleep
      related breathing disorders. DESIGN: In 20 children with PWS who underwent a
      metyrapone test (30 mg/kg at 2330 h), sleep-related breathing was evaluated by
      polysomnography before the metyrapone test. In addition, we recorded sleep
      related breathing in 10 children with PWS during their metyrapone test. CAI was
      diagnosed when ACTH levels during the metyrapone test were below 33 pmol/liter at
      0730 h. All tests were performed during healthy condition. SETTING: The study was
      conducted in a pediatric intensive care unit and specialized sleep center.
      RESULTS: Median (interquartile range) age was 8.4 yr (6.5-10.2). After metyrapone
      administration, median (interquartile range) central apnea index (number/hour)
      increased significantly from 2.2 (0.4-4.7) to 5.2 (1.5-7.9) (P = 0.007). The
      increase tended to be higher in children with CAI [2.8 (2.0-3.9) vs. 1.0 (-0.2 to
      2.6); P = 0.09]. During polysomnography before the metyrapone test, sleep-related
      breathing was worse in children with CAI, who had a significantly higher central
      apnea index and tended to have a lower minimum oxygen saturation compared to
      those without CAI (P = 0.03 and P = 0.07). CONCLUSIONS: In children with PWS, the
      central apnea index increased significantly after metyrapone administration,
      particularly in those with CAI during stress. In addition, children with CAI had
      a higher central apnea index compared to those without several months before the
      metyrapone test.

PMID- 19383776
TI  - The paradoxical increase in cortisol secretion induced by dexamethasone in
      primary pigmented nodular adrenocortical disease involves a glucocorticoid
      receptor-mediated effect of dexamethasone on protein kinase A catalytic subunits.
AB  - CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD) results in most
      cases from mutations of the protein kinase A (PKA) regulatory subunit 1A
      (PRKAR1A) gene. Patients with PPNAD exhibit a paradoxical increase in cortisol
      secretion in response to dexamethasone. OBJECTIVE: The aim was to investigate the
      mechanism of the action of dexamethasone on adrenocortical cells removed from
      patients with PPNAD and a transgenic model of PPNAD [Tg(tTA/X2AS) mice]. DESIGN
      AND SETTING: We performed an in vitro study in an academic research laboratory.
      PATIENTS: Eleven patients with histologically proven PPNAD were included in the
      study. INTERVENTION: Cultured PPNAD cells were incubated with dexamethasone in
      the presence of various modulators of the cAMP/PKA pathway and the glucocorticoid
      receptor antagonist RU486. MAIN OUTCOME MEASURE: Cortisol and corticosterone were
      measured by radioimmunological assays in cell culture supernatants. RESULTS:
      Dexamethasone stimulated in vitro cortisol secretion from PPNAD tissues in six
      patients. The stimulatory effect of dexamethasone on cortisol release was not
      reduced by the adenylyl cyclase inhibitor SQ22536 or potentiated by the
      phosphodiesterase inhibitor IMBX and the cAMP analog 8Br-cAMP. Conversely, the
      PKA inhibitor H89 and RU486 inhibited the cortisol response to dexamethasone.
      Dexamethasone had no effect on cortisol production from normal human
      adrenocortical cells but stimulated corticosteroidogenesis in the presence of
      RU486. Similarly, dexamethasone failed to influence corticosterone release by
      adrenocortical cells removed from Tg(tTA/X2AS) mice but stimulated
      corticosteroidogenesis in the presence of RU 486. CONCLUSIONS: These results
      indicate that, in human PPNAD tissues, dexamethasone paradoxically stimulates
      cortisol release through a glucocorticoid receptor-mediated effect on PKA
      catalytic subunits.

PMID- 19383778
TI  - Clinical review: Realistic expectations and practical use of continuous glucose
      monitoring for the endocrinologist.
AB  - CONTEXT: Real-time continuous glucose monitoring (CGM) has been available for
      type 1 diabetes for several years. This paper is a status report on our early
      experiences with this next technology. EVIDENCE ACQUISITION: The two major
      sources of data acquisition included PubMed search strategies and personal
      experience of the author from clinical experience. EVIDENCE SYNTHESIS: Data
      assessing CGM accuracy, short-term outcomes (12 wk), and longer term outcomes (6
      months) are reported. Potential strategies for successful and efficient use in an
      office or clinic setting are also discussed. Practical aspects of CGM use (alarm
      settings, using glycemic trending information) are also reviewed. CONCLUSIONS:
      Accuracy of this technology has improved in the short amount of time it has been
      available. Six-month data suggest that patient selection is a key for success.
      Patients who do not understand or practice the basics of intensive insulin
      therapy have the greatest challenges. Those who do best watch the receiver
      frequently, continue with frequent home blood glucose monitoring, use the
      trending information to make insulin adjustments, and understand the limitations
      of the technology. With insurance reimbursement improving, CGM is gaining
      acceptance as an important tool for the management of type 1 diabetes. Like home
      blood glucose monitoring and insulin pump therapy, this technology by itself is
      not a panacea for diabetes control. However, it further adds to our ability to
      improve the lives of people with diabetes. Long-term, the hope is that this
      technology will pave the way for a "closed-loop" device.

PMID- 19383779
TI  - Higher serum 25-hydroxyvitamin D levels in school-age children are inconsistently
      associated with increased calcium absorption.
AB  - CONTEXT: Increasing serum 25-hydroxyvitamin D (25-OHD) in adults may enhance
      calcium absorption (Ca-abs). There are few similar pediatric data leading to
      uncertainty about the optimal target for 25-OHD to maximize Ca-abs. OBJECTIVE:
      Our objective was to evaluate the relationship between 25-OHD and Ca-abs in a
      large cohort of school-age children and adolescents. DESIGN: We evaluated data
      from 439 Ca-abs measurements performed using dual-tracer stable isotope
      techniques conducted at our center over a 15-yr period in 251 healthy children,
      4.9-16.7 yr of age. RESULTS: Serum 25-OHD ranged from 28 to 197 nmol/liter (mean
      85 +/- 2 nmol/liter) (sem). Total Ca-abs (intake times fractional absorption)
      were significantly correlated to 25-OHD in the whole population (r = 0.16, P =
      0.001). This relationship was closer in the 197 studies in early puberty (Tanner
      2 or 3, r = 0.35, P < 0.001) and not significant in pre- or late pubertal
      subjects. For the whole population, fractional Ca-abs adjusted for calcium intake
      were slightly but significantly higher at 25-OHD of 28-50 nmol/liter (0.344 +/-
      0.019) compared with 25-OHD of 50-80 nmol/liter (0.280 +/- 0.014) or 25-OHD
      greater than 80 nmol/liter (0.297 +/- 0.015, P < 0.01 for each), suggesting
      adaptation to moderately low 25-OHD values. CONCLUSION: There is no consistent
      pattern of relationship between 25-OHD and either fractional or total calcium
      absorption in school-age children. However, there appears to be a modest calcium
      absorptive response to higher 25-OHD during early puberty.

PMID- 19383780
TI  - Pentosidine and increased fracture risk in older adults with type 2 diabetes.
AB  - CONTEXT: Type 2 diabetes is associated with higher fracture risk at a given bone
      mineral density. Advanced glycation endproducts (AGEs) accumulate in bone
      collagen with age and diabetes and may weaken bone. OBJECTIVE: The aim was to
      determine whether urine pentosidine, an AGE, was associated with fractures in
      older adults with and without diabetes. DESIGN: We performed an observational
      cohort study. SETTING: We used data from the Health, Aging and Body Composition
      prospective study of white and black, well-functioning men and women ages 70-79
      yr. PARTICIPANTS: Participants with (n = 501) and without (n = 427) diabetes were
      matched on gender, race, and study site. PREDICTOR: Urine pentosidine was assayed
      from frozen stored baseline specimens. MAIN OUTCOME MEASURES: Incident clinical
      fractures and baseline vertebral fractures were measured. RESULTS: Despite higher
      bone mineral density, clinical fracture incidence (14.8 vs. 12.6%) and vertebral
      fracture prevalence (2.3 vs. 2.9%) were not lower in those with diabetes (P >
      0.05). In multivariable models, pentosidine was associated with increased
      clinical fracture incidence in those with diabetes [relative hazard, 1.42; 95%
      confidence interval (CI), 1.10, 1.83, for 1 sd increase in log pentosidine] but
      not in those without diabetes (relative hazard, 1.08; 95% CI, 0.79, 1.49; P value
      for interaction = 0.030). In those with diabetes, pentosidine was associated with
      increased vertebral fracture prevalence (adjusted odds ratio, 5.93; 95% CI, 2.08,
      16.94, for 1 sd increase in log pentosidine) but not in those without diabetes
      (adjusted odds ratio, 0.74; 95% CI, 0.30, 1.83; P value for interaction = 0.005).
      CONCLUSIONS: Higher pentosidine levels are a risk factor for fracture in older
      adults with diabetes and may account in part for reduced bone strength in type 2
      diabetes.

PMID- 19383781
TI  - Thyroid gene expression in familial nonautoimmune hyperthyroidism shows common
      characteristics with hyperfunctioning autonomous adenomas.
AB  - CONTEXT: Dominant activating mutations of the TSH receptor are the cause of
      familial nonautoimmune hyperthyroidism (FNAH) (inherited mutations affecting the
      whole gland since embryogenesis) and the majority of hyperfunctioning autonomous
      adenomas (AAs) (somatic mutations affecting only one cell later in the
      adulthood). OBJECTIVE: The objective of the study was defining the functional and
      molecular phenotypes of FNAH and comparing them with the ones of AA. DESIGN:
      Functional phenotypes were determined in vitro and molecular phenotypes by
      hybridization on microarray slides. PATIENTS: Nine patients with FNAH were
      investigated, six for functional in vitro study of the tissue and five for gene
      expression. RESULTS: Iodide metabolism, H(2)O(2), cAMP, and inositol phosphate
      generation in FNAH slices stimulated or not with TSH were normal. The mitogenic
      response of cultured FNAH thyrocytes to TSH was normal but more sensitive to the
      hormone. Gene expression profiles of FNAH and AAs showed that among 474 genes
      significantly regulated in FNAH, 93% were similarly regulated in AAs. Besides,
      783 genes were regulated only in AAs. Bioinformatic analysis pointed out common
      down-regulations of genes involved in immune response, cell/cell and cell/matrix
      adhesions, and apoptosis. Pathways up-regulated only in AAs mainly involve
      diverse biosyntheses. These results are consonant with the larger growth of AAs
      than FNAH tissues. CONCLUSIONS: Whether hereditary or somatic after birth,
      activating mutations of the TSH receptor have the same qualitative consequences
      on the thyroid cell phenotype, but somatic mutations in AAs have a much stronger
      effect than FNAH mutations. Both are variants of one disease: genetic
      hyperthyroidism.

PMID- 19383782
TI  - Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic
      efficacy for murine models of colon cancer.
AB  - IL-15 has potential as an immunotherapeutic agent for cancer treatment because it
      is a critical factor for the proliferation and activation of natural killer (NK)
      and CD8(+) T cells. Administration of anti-CD40 antibodies has shown anti-tumor
      effects in vivo through a variety of mechanisms. Furthermore, activation of CD40
      led to increased expression of IL-15 receptor-alpha by dendritic cells, an action
      that is critical for trans-presentation of IL-15 to NK and CD8(+) T cells. In
      this study, we investigated the therapeutic efficacy of the combination regimen
      of murine IL-15 (mIL-15) with an agonistic anti-CD40 antibody (FGK4.5) in murine
      lung metastasis models involving CT26 and MC38, which are murine colon cancer
      cell lines syngeneic to BALB/c and C57BL/6 mice, respectively. Treatment with mIL
      15 or the anti-CD40 antibody alone significantly prolonged survival of both CT26
      and MC38 tumor-bearing mice compared with the mice in the PBS solution control
      group (P < 0.01). Furthermore, combination therapy with both mIL-15 and the anti
      CD40 antibody provided greater therapeutic efficacy as demonstrated by prolonged
      survival of the mice compared with either mIL-15 or the anti-CD40 antibody-alone
      groups (P < 0.001). We found that NK cells isolated from the mice that received
      the combination regimen expressed increased levels of intracellular granzyme B
      and showed stronger cytotoxic activity on the target cells. The findings from
      this study provide the scientific basis for clinical trials using the combination
      regimen of IL-15 with an anti-CD40 antibody for the treatment of patients with
      cancer.

PMID- 19383783
TI  - Muscle hypertrophy driven by myostatin blockade does not require stem/precursor
      cell activity.
AB  - Myostatin, a member of the TGF-beta family, has been identified as a powerful
      inhibitor of muscle growth. Absence or blockade of myostatin induces massive
      skeletal muscle hypertrophy that is widely attributed to proliferation of the
      population of muscle fiber-associated satellite cells that have been identified
      as the principle source of new muscle tissue during growth and regeneration.
      Postnatal blockade of myostatin has been proposed as a basis for therapeutic
      strategies to combat muscle loss in genetic and acquired myopathies. But this
      approach, according to the accepted mechanism, would raise the threat of
      premature exhaustion of the pool of satellite cells and eventual failure of
      muscle regeneration. Here, we show that hypertrophy in the absence of myostatin
      involves little or no input from satellite cells. Hypertrophic fibers contain no
      more myonuclei or satellite cells and myostatin had no significant effect on
      satellite cell proliferation in vitro, while expression of myostatin receptors
      dropped to the limits of detectability in postnatal satellite cells. Moreover,
      hypertrophy of dystrophic muscle arising from myostatin blockade was achieved
      without any apparent enhancement of contribution of myonuclei from satellite
      cells. These findings contradict the accepted model of myostatin-based control of
      size of postnatal muscle and reorient fundamental investigations away from the
      mechanisms that control satellite cell proliferation and toward those that
      increase myonuclear domain, by modulating synthesis and turnover of structural
      muscle fiber proteins. It predicts too that any benefits of myostatin blockade in
      chronic myopathies are unlikely to impose any extra stress on the satellite
      cells.

PMID- 19383784
TI  - Netrin-1-alpha3beta1 integrin interactions regulate the migration of interneurons
      through the cortical marginal zone.
AB  - Cortical GABAergic interneurons, most of which originate in the ganglionic
      eminences, take distinct tangential migratory trajectories into the developing
      cerebral cortex. However, the ligand-receptor systems that modulate the
      tangential migration of distinct groups of interneurons into the emerging
      cerebral wall remain unclear. Here, we show that netrin-1, a diffusible guidance
      cue expressed along the migratory routes traversed by GABAergic interneurons,
      interacts with alpha3beta1 integrin to promote interneuronal migration. In vivo
      analysis of interneuron-specific alpha3beta1 integrin, netrin-1-deficient mice
      (alpha3(lox/-)Dlx5/6-CIE, netrin-1(-/-)) reveals specific deficits in the
      patterns of interneuronal migration along the top of the developing cortical
      plate, resulting in aberrant interneuronal positioning throughout the cerebral
      cortex and hippocampus of conditional alpha3(lox/-)Dlx5/6-CIE, netrin-1(-/-)
      mice. These results indicate that specific guidance mechanisms, such as netrin-1
      alpha3beta1 integrin interactions, modulate distinct routes of interneuronal
      migration and the consequent positioning of groups of cortical interneurons in
      the developing cerebral cortex.

PMID- 19383785
TI  - Three related receptor-like kinases are required for optimal cell elongation in
      Arabidopsis thaliana.
AB  - Cell elongation in plants is controlled by environmental cues such as light and
      internal growth regulators including plant steroid hormones, brassinosteroids
      (BRs). In this study, we found that 3 related receptor-like kinases (RLKs),
      HERCULES1, THESEUS1, and FERONIA, are transcriptionally induced by BRs and are
      down-regulated in the loss-of-function BR mutant bri1 and up-regulated in the
      constitutive BR-response mutant bes1-D. These RLKs belong to the CrRLK family
      that has 17 members in Arabidopsis. We hypothesize that these RLKs are involved
      in BR-regulated processes. Although 2 of the RLKs were recently found to mediate
      male-female interaction during pollen tube reception (FERONIA) and to sense cell
      wall integrity (THESEUS1), our genetic studies demonstrated that they are
      required for cell elongation during vegetative growth as herk1 the1 double and
      fer RNAi mutants displayed striking dwarf phenotypes. The herk1 the1 double
      mutant enhances the dwarf phenotype of bri1 and partially suppresses bes1-D
      phenotype, supporting a role of HERK1/THE1 in BR-mediated cell elongation.
      Microarray experiments demonstrated that these RLKs control the expression of a
      unique set of genes including those implicated in cell elongation and 16% of the
      genes affected in herk1 the1 are regulated by BRs. Our results, therefore,
      identify a previously unknown pathway that functions cooperatively with, but
      largely independent of the BR pathway to regulate cell elongation. The work
      establishes a platform to identify other signaling components in this important
      pathway for plant growth and provides a paradigm to study the coordination of
      independent pathways in the regulation of a common biological process.

PMID- 19383786
TI  - Antigen-specific Vgamma2Vdelta2 T effector cells confer homeostatic protection
      against pneumonic plaque lesions.
AB  - The possibility that Vgamma2Vdelta2 T effector cells can confer protection
      against pulmonary infectious diseases has not been tested. We have recently
      demonstrated that single-dose (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate
      (HMBPP) plus IL-2 treatment can induce prolonged accumulation of Vgamma2Vdelta2 T
      effector cells in lungs. Here, we show that a delayed HMBPP/IL-2 administration
      after inhalational Yersinia pestis infection induced marked expansion of
      Vgamma2Vdelta2 T cells but failed to control extracellular plague bacterial
      replication/infection. Surprisingly, despite the absence of infection control,
      expansion of Vgamma2Vdelta2 T cells after HMBPP/IL-2 treatment led to the
      attenuation of inhalation plague lesions in lungs. Consistently, HMBPP-activated
      Vgamma2Vdelta2 T cells accumulated and localized in pulmonary interstitials
      surrounding small blood vessels and airway mucosa in the lung tissues with no or
      mild plague lesions. These infiltrating Vgamma2Vdelta2 T cells produced FGF-7, a
      homeostatic mediator against tissue damages. In contrast, control macaques
      treated with glucose plus IL-2 or glucose alone exhibited severe hemorrhages and
      necrosis in most lung lobes, with no or very few Vgamma2Vdelta2 T cells
      detectable in lung tissues. The findings are consist with the paradigm that
      circulating Vgamma2Vdelta2 T cells can traffic to lungs for homeostatic
      protection against tissue damages in infection.

PMID- 19383787
TI  - Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity.
AB  - Inclusions of TAR DNA-binding protein-43 (TDP-43), a nuclear protein that
      regulates transcription and RNA splicing, are the defining histopathological
      feature of frontotemporal lobar degeneration with ubiquitin-positive inclusions
      (FTLD-Us) and sporadic and familial forms of amyotrophic lateral sclerosis (ALS).
      In ALS and FTLD-U, aggregated, ubiquitinated, and N-terminally truncated TDP-43
      can be isolated from brain tissue rich in neuronal and glial cytoplasmic
      inclusions. The loss of TDP-43 function resulting from inappropriate cleavage,
      translocation from the nucleus, or its sequestration into inclusions could play
      important roles in neurodegeneration. However, it is not known whether TDP-43
      fragments directly mediate toxicity and, more specifically, whether their
      abnormal aggregation is a cause or consequence of pathogenesis. We report that
      the ectopic expression of a approximately 25-kDa TDP-43 fragment corresponding to
      the C-terminal truncation product of caspase-cleaved TDP-43 leads to the
      formation of toxic, insoluble, and ubiquitin- and phospho-positive cytoplasmic
      inclusions within cells. The 25-kDa C-terminal fragment is more prone to
      phosphorylation at S409/S410 than full-length TDP-43, but phosphorylation at
      these sites is not required for inclusion formation or toxicity. Although this
      fragment shows no biological activity, its exogenous expression neither inhibits
      the function nor causes the sequestration of full-length nuclear TDP-43,
      suggesting that the 25-kDa fragment can induce cell death through a toxic gain-of
      function. Finally, by generating a conformation-dependent antibody that detects C
      terminal fragments, we show that this toxic cleavage product is specific for
      pathologic inclusions in human TDP-43 proteinopathies.

PMID- 19383788
TI  - ERalpha as ligand-independent activator of CDH-1 regulates determination and
      maintenance of epithelial morphology in breast cancer cells.
AB  - Estrogen receptor alpha (ERalpha) and E-cadherin are primary markers of luminal
      epithelial breast cancer cells with E-cadherin being a main caretaker of the
      epithelial phenotype. E-cadherin repression is needed for cancer cells to acquire
      motile and invasive properties, and it is known that in ER-positive breast cancer
      cells, estrogen down-regulate E-cadherin gene transcription. We report here that
      ERalpha is bound to the E-cadherin promoter in both the presence and the complete
      absence of estrogen, suggesting an unexpected role for unliganded ERalpha in E
      cadherin transcription. Indeed, our data reveal that activation by unliganded
      ERalpha and repression by estrogen-activated ERalpha require direct binding to a
      half-estrogen response element within the E-cadherin promoter and exchange from
      associated coactivators to corepressors. Therefore, these results suggest a
      pivotal role for unliganded ERalpha in controlling a fundamental caretaker of the
      epithelial phenotype in breast cancer cells. Here, we show that ERalpha-positive
      breast cancer T47D cells transduced with the sfRON kinase undergo a full
      epithelial-mesenchymal conversion and lose E-cadherin and ERalpha expression. Our
      data show that, although the E-cadherin gene becomes hypermethylated and
      heterochromatic, kinase inhibitors can restore E-cadherin expression, together
      with an epithelial morphology in an ERalpha-dependent fashion. Similarly,
      transfection of ERalpha, in the absence of ligands, was sufficient to restore E
      cadherin transcription in both sfRON-T47D and other ERalpha-, E-cadherin-negative
      cells. Therefore, our results suggest a novel role for the ERalpha that plays the
      dual role of ligand-independent activator and ligand-dependent repressor of E
      cadherin in breast cancer cells.

PMID- 19383789
TI  - Efficient production of mesencephalic dopamine neurons by Lmx1a expression in
      embryonic stem cells.
AB  - Signaling factors involved in CNS development have been used to control the
      differentiation of embryonic stem cells (ESCs) into mesencephalic dopamine
      (mesDA) neurons, but tend to generate a limited yield of desired cell type. Here
      we show that forced expression of Lmx1a, a transcription factor functioning as a
      determinant of mesDA neurons during embryogenesis, effectively can promote the
      generation of mesDA neurons from mouse and human ESCs. Under permissive culture
      conditions, 75%-95% of mouse ESC-derived neurons express molecular and
      physiological properties characteristic of bona fide mesDA neurons. Similar to
      primary mesDA neurons, these cells integrate and innervate the striatum of 6
      hydroxy dopamine lesioned neonatal rats. Thus, the enriched generation of
      functional mesDA neurons by forced expression of Lmx1a may be of future
      importance in cell replacement therapy of Parkinson disease.

PMID- 19383790
TI  - Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductance.
AB  - Aquaporin (AQP) 4 is the predominant water channel in the mammalian brain,
      abundantly expressed in the blood-brain and brain-cerebrospinal fluid interfaces
      of glial cells. Its function in cerebral water balance has implications in
      neuropathological disorders, including brain edema, stroke, and head injuries.
      The 1.8-A crystal structure reveals the molecular basis for the water selectivity
      of the channel. Unlike the case in the structures of water-selective AQPs AqpZ
      and AQP1, the asparagines of the 2 Asn-Pro-Ala motifs do not hydrogen bond to the
      same water molecule; instead, they bond to 2 different water molecules in the
      center of the channel. Molecular dynamics simulations were performed to ask how
      this observation bears on the proposed mechanisms for how AQPs remain totally
      insulating to any proton conductance while maintaining a single file of hydrogen
      bonded water molecules throughout the channel.

PMID- 19383791
TI  - Earliest domestication of common millet (Panicum miliaceum) in East Asia extended
      to 10,000 years ago.
AB  - The origin of millet from Neolithic China has generally been accepted, but it
      remains unknown whether common millet (Panicum miliaceum) or foxtail millet
      (Setaria italica) was the first species domesticated. Nor do we know the timing
      of their domestication and their routes of dispersal. Here, we report the
      discovery of husk phytoliths and biomolecular components identifiable solely as
      common millet from newly excavated storage pits at the Neolithic Cishan site,
      China, dated to between ca. 10,300 and ca. 8,700 calibrated years before present
      (cal yr BP). After ca. 8,700 cal yr BP, the grain crops began to contain a small
      quantity of foxtail millet. Our research reveals that the common millet was the
      earliest dry farming crop in East Asia, which is probably attributed to its
      excellent resistance to drought.

PMID- 19383792
TI  - Electrophysiological characterization of LacY.
AB  - Electrogenic events due to the activity of wild-type lactose permease from
      Escherichia coli (LacY) were investigated with proteoliposomes containing
      purified LacY adsorbed on a solid-supported membrane electrode. Downhill
      sugar/H(+) symport into the proteoliposomes generates transient currents. Studies
      at different lipid-to-protein ratios and at different pH values, as well as
      inactivation by N-ethylmaleimide, show that the currents are due specifically to
      the activity of LacY. From analysis of the currents under different conditions
      and comparison with biochemical data, it is suggested that the predominant
      electrogenic event in downhill sugar/H(+) symport is H(+) release. In contrast,
      LacY mutants Glu-325-->Ala and Cys-154-->Gly, which bind ligand normally, but are
      severely defective with respect to lactose/H(+) symport, exhibit only a small
      electrogenic event on addition of LacY-specific substrates, representing 6% of
      the total charge displacement of the wild-type. This activity is due either to
      substrate binding per se or to a conformational transition after substrate
      binding, and is not due to sugar/H(+) symport. We propose that turnover of LacY
      involves at least 2 electrogenic reactions: (i) a minor electrogenic step that
      occurs on sugar binding and is due to a conformational transition in LacY; and
      (ii) a major electrogenic step probably due to cytoplasmic release of H(+) during
      downhill sugar/H(+) symport, which is the limiting step for this mode of
      transport.

PMID- 19383793
TI  - Regulated expression of the Leishmania major surface virulence factor
      lipophosphoglycan using conditionally destabilized fusion proteins.
AB  - Surface glycoconjugates play important roles in the infectious cycle of
      Leishmania major, including the abundant lipophosphoglycan (LPG) implicated in
      parasite survival in the sand fly vector and the initial stages of establishment
      in the mammalian host macrophage. We describe a system for inducible expression
      of LPG, applying a novel protein-based system that allows controlled degradation
      of a key LPG biosynthetic enzyme, UDP-galactopyranose mutase (UGM). This
      methodology relies on a mutated FK506-binding protein (FKBP) destabilizing domain
      (dd) fused to the protein of interest; in the absence of rapamycin analogs, such
      as Shld1, the dd domain is destabilized, leading to proteasomal degradation,
      whereas drug treatment confers stabilization. Tests in L. major using dd fusions
      to a panel of reporters and cellular proteins confirmed its functionality, with a
      high degree of regulation and low background, and we established the kinetics of
      protein activation and/or loss. Two inexpensive and widely available ligands,
      FK506 and rapamycin, functioned similarly to Shld1, without effect on Leishmania
      growth or differentiation. We generated parasites lacking UGM through deletion of
      the GLF gene and substitution with a ddGLF fusion construct, either as
      chromosomal knockins or through episomal complementation; these showed little or
      no LPG expression in the absence of inducer, whereas in its presence, high levels
      of LPG were attained rapidly. Complement lysis tests confirmed the correct
      integrity of the Leishmania LPG coat. These data suggest that the dd approach has
      great promise in the study of LPG and other pathways relevant to parasite
      survival and virulence.

PMID- 19383794
TI  - Mechanism of drug inhibition and drug resistance of influenza A M2 channel.
AB  - The influenza A virus M2 proton channel equilibrates pH across the viral membrane
      during entry and across the trans-Golgi membrane of infected cells during viral
      maturation. It is an important target of adamantane-family antiviral drugs, but
      drug resistance has become a critical problem. Two different sites for drug
      interaction have been proposed. One is a lipid-facing pocket between 2 adjacent
      transmembrane helices (around Asp-44), at which the drug binds and inhibits
      proton conductance allosterically. The other is inside the pore (around Ser-31),
      at which the drug directly blocks proton passage. Here, we describe structural
      and functional experiments on the mechanism of drug inhibition and resistance.
      The solution structure of the S31N drug-resistant mutant of M2, a mutant of the
      highly pathogenic avian influenza subtype H5N1, shows that replacing Ser-31 with
      Asn has little effect on the structure of the channel pore, but dramatically
      reduces drug binding to the allosteric site. Mutagenesis and liposomal proton
      flux assays show that replacing the key residue (Asp-44) in the lipid-facing
      binding pocket with Ala has a dramatic effect on drug sensitivity, but that the
      channel remains fully drug sensitive when replacing Ser-31 with Ala. Chemical
      cross-linking studies indicate an inverse correlation between channel stability
      and drug resistance. The lipid-facing pocket contains residues from 2 adjacent
      channel-forming helices. Therefore, it is present only when the helices are
      tightly packed in the closed conformation. Thus, drug-resistant mutants impair
      drug binding by destabilizing helix-helix assembly.

PMID- 19383795
TI  - Simulating the electrostatic guidance of the vectorial translocations in
      hexameric helicases and translocases.
AB  - The molecular origin of the action of helicases is explored, starting with a
      model built based on the different X-ray structures of the large tumor antigen
      (LTag) hexameric helicase and a simplified model containing the ionized phosphate
      backbones of a single-strand DNA. The coupling between the protein structural
      changes and the translocation process is quantified using an effective
      electrostatic free-energy surface for the protein/DNA complex. This surface is
      then used in Langevin dynamics simulations of the time dependence of the
      translocation process. Remarkably, the simulated motion along the free-energy
      surface results in a vectorial translocation of the DNA, consistent with the
      biological process. The electrostatic energy of the system appears to reproduce
      the directionality of this process. Thus, we are able to provide a consistent
      structure-based molecular description of the energetic and dynamics of the
      translocation process. This analysis may have general implications for relating
      structural models to translocation directionality in helicases and other DNA
      translocases.

PMID- 19383796
TI  - Ablation of triadin causes loss of cardiac Ca2+ release units, impaired
      excitation-contraction coupling, and cardiac arrhythmias.
AB  - Heart muscle excitation-contraction (E-C) coupling is governed by Ca(2+) release
      units (CRUs) whereby Ca(2+) influx via L-type Ca(2+) channels (Cav1.2) triggers
      Ca(2+) release from juxtaposed Ca(2+) release channels (RyR2) located in
      junctional sarcoplasmic reticulum (jSR). Although studies suggest that the jSR
      protein triadin anchors cardiac calsequestrin (Casq2) to RyR2, its contribution
      to E-C coupling remains unclear. Here, we identify the role of triadin using mice
      with ablation of the Trdn gene (Trdn(-/-)). The structure and protein composition
      of the cardiac CRU is significantly altered in Trdn(-/-) hearts. jSR proteins
      (RyR2, Casq2, junctin, and junctophilin 1 and 2) are significantly reduced in
      Trdn(-/-) hearts, whereas Cav1.2 and SERCA2a remain unchanged. Electron
      microscopy shows fragmentation and an overall 50% reduction in the contacts
      between jSR and T-tubules. Immunolabeling experiments show reduced colocalization
      of Cav1.2 with RyR2 and substantial Casq2 labeling outside of the jSR in Trdn(-/
      ) myocytes. CRU function is impaired in Trdn(-/-) myocytes, with reduced SR
      Ca(2+) release and impaired negative feedback of SR Ca(2+) release on Cav1.2
      Ca(2+) currents (I(Ca)). Uninhibited Ca(2+) influx via I(Ca) likely contributes
      to Ca(2+) overload and results in spontaneous SR Ca(2+) releases upon beta
      adrenergic receptor stimulation with isoproterenol in Trdn(-/-) myocytes, and
      ventricular arrhythmias in Trdn(-/-) mice. We conclude that triadin is critically
      important for maintaining the structural and functional integrity of the cardiac
      CRU; triadin loss and the resulting alterations in CRU structure and protein
      composition impairs E-C coupling and renders hearts susceptible to ventricular
      arrhythmias.

PMID- 19383797
TI  - Fine mapping and functional analysis of a common variant in MSMB on chromosome
      10q11.2 associated with prostate cancer susceptibility.
AB  - Two recent genome-wide association studies have independently identified a
      prostate cancer susceptibility locus on chromosome 10q11.2. The most significant
      single-nucleotide polymorphism (SNP) marker reported, rs10993994, is 57 bp
      centromeric of the first exon of the MSMB gene, which encodes beta
      microseminoprotein (prostatic secretory protein 94). In this study, a fine
      mapping analysis using HapMap SNPs was conducted across a approximately 65-kb
      region (chr10: 51168330-51234020) flanking rs10993994 with 13 tag SNPs in 6,118
      prostate cancer cases and 6,105 controls of European origin from the Cancer
      Genetic Markers of Susceptibility (CGEMS) project. rs10993994 remained the most
      strongly associated marker with prostate cancer risk [P = 8.8 x 10(-18);
      heterozygous odds ratio (OR) = 1.20, 95% confidence interval (CI): 1.11-1.30;
      homozygous OR = 1.64, 95% CI: 1.47-1.86 for the adjusted genotype test with 2
      df]. In follow-up functional analyses, the T variant of rs10993994 significantly
      affected expression of in vitro luciferase reporter constructs. In
      electrophoretic mobility shift assays, the C allele of rs10993994 preferentially
      binds to the CREB transcription factor. Analysis of tumor cell lines with a CC or
      CT genotype revealed a high level of MSMB gene expression compared with cell
      lines with a TT genotype. These findings were specific to the alleles of
      rs10993994 and were not observed for other SNPs determined by sequence analysis
      of the proximal promoter. Together, our mapping study and functional analyses
      implicate regulation of expression of MSMB as a plausible mechanism accounting
      for the association identified at this locus. Further investigation is warranted
      to determine whether rs10993994 alone or in combination with additional variants
      contributes to prostate cancer susceptibility.

PMID- 19383798
TI  - Nanoparticle-mediated targeting of MAPK signaling predisposes tumor to
      chemotherapy.
AB  - The MAPK signal transduction cascade is dysregulated in a majority of human
      tumors. Here we report that a nanoparticle-mediated targeting of this pathway can
      optimize cancer chemotherapy. We engineered nanoparticles from a unique
      hexadentate-polyD,L-lactic acid-co-glycolic acid polymer chemically conjugated to
      PD98059, a selective MAPK inhibitor. The nanoparticles are taken up by cancer
      cells through endocytosis and demonstrate sustained release of the active agent,
      resulting in the inhibition of phosphorylation of downstream extracellular signal
      regulated kinase. We demonstrate that nanoparticle-mediated targeting of MAPK
      inhibits the proliferation of melanoma and lung carcinoma cells and induces
      apoptosis in vitro. Administration of the PD98059-nanoparticles in melanoma
      bearing mice inhibits tumor growth and enhances the antitumor efficacy of
      cisplatin chemotherapy. Our study shows the nanoparticle-mediated delivery of
      signal transduction inhibitors can emerge as a unique paradigm in cancer
      chemotherapy.

PMID- 19383799
TI  - An ABC transport system that maintains lipid asymmetry in the gram-negative outer
      membrane.
AB  - The outer membranes (OMs) of gram-negative bacteria have an asymmetric lipid
      distribution with lipopolysaccharides at the outer leaflet and phospholipids
      (PLs) at the inner leaflet. This lipid arrangement is essential for the barrier
      function of the OM and for the viability of most gram-negative bacteria. Cells
      with OM assembly defects or cells exposed to harsh chemical treatments accumulate
      PLs in the outer leaflet of the OM and this disrupts lipopolysaccharide
      organization and increases sensitivity to small toxic molecules. We have
      identified an ABC transport system in Escherichia coli with predicted import
      function that serves to prevent PL accumulation in the outer leaflet of the OM.
      This highly conserved pathway, which we have termed the Mla pathway for its role
      in preserving OM lipid asymmetry, is composed of at least 6 proteins and contains
      at least 1 component in each cellular compartment. We propose that the Mla
      pathway constitutes a bacterial intermembrane PL trafficking system.

PMID- 19383800
TI  - Bursting of sensitive polymersomes induced by curling.
AB  - Polymersomes, which are stable and robust vesicles made of block copolymer
      amphiphiles, are good candidates for drug carriers or micro/nanoreactors. Polymer
      chemistry enables almost unlimited molecular design of responsive polymersomes
      whose degradation upon environmental changes has been used for the slow release
      of active species. Here, we propose a strategy to remotely trigger instantaneous
      polymersome bursting. We have designed asymmetric polymer vesicles, in which only
      one leaflet is composed of responsive polymers. In particular, this approach has
      been successfully achieved by using a UV-sensitive liquid-crystalline copolymer.
      We study experimentally and theoretically this bursting mechanism and show that
      it results from a spontaneous curvature of the membrane induced by the remote
      stimulus. The versatility of this mechanism should broaden the range of
      applications of polymersomes in fields such as drug delivery, cosmetics and
      material chemistry.

PMID- 19383802
TI  - Releasing versus ligation of 2 tails of large venous aneurysms secondary to
      dialysis arteriovenous fistulas.

PMID- 19383803
TI  - A methodology for improving throughput using portal monitors.
AB  - The National Internal Radiation Assessment Section (NIRAS), which operates the
      Canadian National Calibration Reference Centre for Bioassay and In Vivo
      Monitoring, has field deployable equipment for emergency response. A substantial
      part of this tool kit is a set of portal monitors that can be used to quickly
      screen people into the 'uncontaminated' and the 'contaminated'. The former term
      refers to a person who has <60 kBq (empirical practical detection limit) of
      activation/fission products and the latter group is contaminated by that amount
      or more. Recent field work has shown that one type of the NIRAS's portal monitors
      can be alarmed at significant distances if the level of contamination is high
      enough. The other types, which do not initiate a count until either an infra-red
      beam is broken or a proximity detector is activated, do not alarm but their
      background will be raised and this causes other problems. This paper proposes a
      method of group monitoring to help speed up the process of screening a large
      number of potentially contaminated persons using portal monitors. In short, the
      group of potentially contaminated persons will be kept isolated from the portal
      stations. Depending on a real-time estimate of the percentage of contaminated
      persons in the crowd, groups of persons will be selected for screening. The
      hypergeometric distribution has been used to decide on the sampling group size
      with an expectation that 90% of the time no contaminated person will be present
      in the group. Once removed from the main waiting area, the group will be pre
      screened and then, depending on the result, sent to the appropriate portal. It is
      anticipated that this will greatly speed up processing as it substantially
      reduces the transit time. Transits times have also been estimated in addition to
      the number of personnel required to run all of NIRAS's field deployable
      equipment.

PMID- 19383804
TI  - Evaluation of an enzyme immunoassay for plasma-free metanephrines in the
      diagnosis of catecholamine-secreting tumors.
AB  - OBJECTIVE: To define the test characteristics of an enzyme immunoassay (EIA) for
      plasma-free metanephrines (metanephrine and normetanephrine) in the diagnosis of
      pheochromocytoma and paraganglioma. DESIGN: Prospective observational design from
      a single University Hospital. Twenty-four hour urine for catecholamines and
      plasma for free metanephrines were collected from patients with a clinical
      suspicion of pheochromocytoma or paraganglioma. Patient records were reviewed for
      clinical data, follow-up, imaging and laboratory results to establish or exclude
      the diagnosis of pheochromocytoma. PATIENTS AND METHODS: Out of 178 consecutive
      patients, 10 had a paraganglioma and 12 had a pheochromocytoma: 156 were finally
      judged not to harbour active tumors and were therefore considered as controls.
      The main outcome measure was the diagnosis or exclusion of paraganglioma or
      pheochromocytoma and test characteristics of plasma-free metanephrines measured
      by EIA. RESULTS: Urinary epinephrine had a sensitivity of 45.5% and
      norepinephrine a sensitivity of 75% (98.8% specificity) for the diagnosis of
      pheochromocytoma. Plasma-free metanephrine and normetanephrine both had a
      sensitivity of 66.7% and a specificity of 100%, but when combined (either
      positive) they demonstrated a 91.7% sensitivity with a preserved specificity of
      100%. For the diagnosis of paraganglioma, urinary norepinephrine gave slightly
      better results than plasma-free metanephrines, but combined testing was of no
      additional value. CONCLUSIONS: Plasma-free metanephrines measured by EIA have
      better diagnostic test characteristics than urinary catecholamines in the
      diagnosis of pheochromocytoma. The EIA offers a simple and effective measurement
      of plasma-free metanephrines.

PMID- 19383805
TI  - Small effect of the androgen receptor gene GGN repeat polymorphism on serum
      testosterone levels in healthy men.
AB  - OBJECTIVE: The human androgen receptor (AR) contains a polyglutamine and a
      polyglycine stretch which are highly polymorphic and are coded respectively by a
      CAG and GGN repeat in exon 1 of the AR gene. Although the in vitro studies
      indicated a possible effect of the GGN repeat polymorphism on the AR gene
      transcription and clinical observations suggest that it might modulate the
      androgen action, its functional significance remains unclear. We wanted to assess
      whether the GGN repeat affects the serum testosterone levels in healthy men,
      which is the expected outcome through feedback regulation if it influences
      androgen action as has been shown to be the case for the CAG repeat. DESIGN AND
      PATIENTS: A population based cross-sectional cohort study including 1476 healthy
      young, middle-aged, and elderly men. MEASUREMENT: Testosterone and LH levels were
      determined by immunoassay; free testosterone (FT) levels were calculated.
      Genotyping of the GGN repeat was performed using the sequencing technique.
      RESULTS: The GGN repeat number was significantly associated with circulating
      testosterone and FT levels (P=0.017 and P=0.013 respectively). However, taking
      into account that age, body mass index, and CAG are already in the regression
      model, the GGN repeat could explain only a small part of the variation of both
      testosterone and FT. CONCLUSION: To our knowledge, this study is the first to
      demonstrate a significant positive association between the GGN repeat and
      androgen levels in a large cohort of healthy men. Although the present study thus
      adds credence to the view that the polyglycine tract in the AR can modulate AR
      action, this effect appears to be only small so that its clinical relevance
      remains questionable.

PMID- 19383806
TI  - Improving glucocorticoid replacement therapy using a novel modified-release
      hydrocortisone tablet: a pharmacokinetic study.
AB  - BACKGROUND: Endogenous plasma cortisol levels have a well-defined circadian
      rhythm. The aim of this project is to develop a once daily oral dual-release
      formulation for cortisol replacement therapy that mimics the diurnal variation in
      the plasma cortisol profile. OBJECTIVE: To determine single-dose plasma
      pharmacokinetics and dose-proportionality of oral 5 and 20 mg dual-release
      hydrocortisone tablets in healthy volunteers. In addition, the effect of food
      intake was investigated for the 20 mg dose. DESIGN: A randomised, controlled, two
      way cross-over, double-blind, phase I study of oral hydrocortisone (modified
      (dual) release; 5 and 20 mg) with an open food-interaction arm. METHODS: The
      single dose pharmacokinetic studies were performed with betamethasone
      suppression. The two first study days were blinded and randomised between morning
      administration of 5 and 20 mg tablet in a fasting state. The third day was open
      with a 20 mg tablet taken 30 min after a high-calorie, high-fat meal. The plasma
      samples were assayed using both a validated LC-MS/MS and an immunoassay. The
      plasma pharmacokinetic variables were calculated using non-compartmental data
      analysis. RESULTS: The time to reach a clinically significant plasma
      concentration of cortisol (>200 nmol/l) was within 20 min and a mean peak of 431
      (s.d. 126) nmol/l was obtained within 50 min after administration of the 20 mg
      tablet. Plasma cortisol levels remained above 200 nmol/l for around 6 h
      thereafter and all plasma concentrations 18-24 h after intake were below 50
      nmol/l. In the fed state the time to reach 200 nmol/l was delayed by 28 and 9 min
      based on LC-MS/MS and immunoassay, respectively. The 5 and 20 mg tablets produced
      an increase in plasma exposure of cortisol that was not fully dose proportional.
      CONCLUSION: The dual release hydrocortisone tablet with once-daily administration
      produced a diurnal plasma cortisol profile mimicking the physiological serum
      cortisol profile.

PMID- 19383807
TI  - Vitamin D therapy in patients with primary hyperparathyroidism and
      hypovitaminosis D.
AB  - OBJECTIVE: To determine whether vitamin D repletion of patients with primary
      hyperparathyroidism (PHPT) and vitamin D deficiency or insufficiency
      (hypovitaminosis D) has deleterious clinical and/or biochemical effects. DESIGN:
      Prospective audit of the effect of vitamin D repletion on biochemical data in 56
      patients with PHPT. Patients were treated with 50,000 units of vitamin D2 weekly
      for 8 weeks with biochemical measurements at 5 and 10 weeks, and subsequently
      after 12 weeks on 800 units of vitamin D3 daily, and in those with
      hypovitaminosis D after 12 weeks of up to 100 000 units of vitamin D(2) monthly.
      METHODS: Serum calcium, albumin, phosphorus, 25-OHD, intact parathyroid hormone
      (PTH) and urine calcium/creatinine (Ca/Cr) ratios were measured before and during
      vitamin D therapy. RESULTS: Patients treated with 50,000 units of vitamin D2
      weekly for 8 weeks resulted in a significant increase in serum 25-OHD levels from
      36.4 to 89.4 nmol/l at 5 weeks (P<0.0001) and 88.6 nmol/l at 10 weeks (P<0.0001).
      There were no significant changes in serum calcium. At 10 weeks, there was a non
      significant decrease in serum PTH and in urine Ca/Cr ratios. None of the patients
      developed any calcium-related adverse events. Subsequently, patients with
      subnormal 25-OHD levels on 800 units of vitamin D daily were treated for the next
      12 weeks with up to 100,000 units of vitamin D2 monthly with normalization of
      serum 25-OHD in all but 4 patients. CONCLUSION: These data fail to demonstrate
      any adverse effects of vitamin D repletion in PHPT.

PMID- 19383808
TI  - Regulation of breast cancer metastasis by atypical chemokine receptors.
AB  - The interaction between chemokines and their G-protein-coupled receptors plays an
      important role in promoting metastasis of different kinds of human cancers.
      However, the expression of an atypical chemokine receptor, CCX-CKR, which serves
      as a decoy receptor to attract chemokines, inhibits the growth and metastasis of
      breast cancer by sequestration of chemokines.

PMID- 19383809
TI  - KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based
      diagnostic system for ALK-positive lung cancer.
AB  - PURPOSE: EML4-ALK is a transforming fusion tyrosine kinase, several isoforms of
      which have been identified in lung cancer. Immunohistochemical detection of EML4
      ALK has proved difficult, however, likely as a result of low transcriptional
      activity conferred by the promoter-enhancer region of EML4. The sensitivity of
      EML4-ALK detection by immunohistochemistry should be increased adequately.
      EXPERIMENTAL DESIGN: We developed an intercalated antibody-enhanced polymer
      (iAEP) method that incorporates an intercalating antibody between the primary
      antibody to ALK and the dextran polymer-based detection reagents. RESULTS: Our
      iAEP method discriminated between tumors positive or negative for EML4-ALK in a
      test set of specimens. Four tumors were also found to be positive for ALK in an
      archive of lung adenocarcinoma (n = 130) and another 4 among fresh cases analyzed
      in a diagnostic laboratory. These 8 tumors were found to include 1 with EML4-ALK
      variant 1, 1 with variant 2, 3 with variant 3, and 2 with previously unidentified
      variants (designated variants 6 and 7). Inverse reverse transcription-PCR
      analysis revealed that the remaining tumor harbored a novel fusion in which
      intron 24 of KIF5B was ligated to intron 19 of ALK. Multiplex reverse
      transcription-PCR analysis of additional archival tumor specimens identified
      another case of lung adenocarcinoma positive for KIF5B-ALK. CONCLUSIONS: The iAEP
      method should prove suitable for immunohistochemical screening of tumors positive
      for ALK or ALK fusion proteins among pathologic archives. Coupling of PCR-based
      detection to the iAEP method should further facilitate the rapid identification
      of novel ALK fusion genes such as KIF5B-ALK.

PMID- 19383810
TI  - The breast cancer susceptibility mutation PALB2 1592delT is associated with an
      aggressive tumor phenotype.
AB  - PURPOSE: To determine the effect of the breast cancer susceptibility mutation
      PALB2 1592delT on tumor phenotype and patient survival. EXPERIMENTAL DESIGN: We
      defined the PALB2 mutation status in 947 familial and 1,274 sporadic breast
      cancer patients and 1,079 population controls, and compared tumor characteristics
      and survival in mutation carriers relative to other familial and sporadic cases
      and to 79 BRCA1 and 104 BRCA2 mutation carrier cases. RESULTS: The PALB2 1592delT
      mutation was found in 19 familial [2.0%; odds ratio, 11.03; 95% confidence
      interval (95% CI), 2.65-97.78; P < 0.0001] and eight sporadic patients (0.6%;
      odds ratio, 3.40; 95% CI, 0.68-32.95; P = 0.1207) compared with two (0.2%)
      control individuals. Tumors of the PALB2 mutation carriers presented triple
      negative (estrogen receptor negative/progesterone receptor negative/HER negative)
      phenotype more often (54.5%; P < 0.0001) than those of other familial (12.2%) or
      sporadic (9.4%) breast cancer patients. They were also more often of higher grade
      (P = 0.0027 and P = 0.0017, respectively) and had higher expression of Ki67 (P =
      0.0004 and P = 0.0490, respectively). Carrying a PALB2 mutation was also
      associated with reduced survival, especially in familial cases (hazard ratio,
      2.30; 95% CI, 1.01-5.24; P = 0.0466) and among familial patients with HER2
      negative tumors (hazard ratio, 4.57; 95% CI, 1.96-10.64; P = 0.0004). Carrying a
      BRCA2 mutation was also found to be an independent predictor of poor survival at
      10-year follow-up (P = 0.04). CONCLUSIONS: The PALB2 1592delT mutation has a
      strong effect on familial breast cancer risk. The tumors rising in patients
      carrying this mutation manifest a phenotype associated with aggressive disease.
      Our results also suggest a significant impact of carrying a BRCA2 mutation on
      long-term breast cancer survival.

PMID- 19383811
TI  - p53 Arg72Pro and MDM2 T309G polymorphisms, histology, and esophageal cancer
      prognosis.
AB  - PURPOSE: This study aimed to evaluate the prognostic significance of two
      functional single nucleotide polymorphisms (SNP) in the p53 pathway (p53 Arg72Pro
      and MDM2 T309G) in patients with esophageal cancer, and to determine the
      importance of histologic subtype in the SNP-outcome relationships. EXPERIMENTAL
      DESIGN: A cohort of 371 patients with esophageal carcinoma enrolled in Boston,
      USA from 1999 to 2004 were genotyped for the p53 and MDM2 SNPs. Associations
      between genotypes and overall survival (OS; the primary outcome) and progression
      free survival (PFS) were assessed using the Kaplan-Meier method. Cox proportional
      hazard models, adjusted for age, stage, performance status, and smoking were
      developed. Interaction analyses were done for histology (adenocarcinoma versus
      squamous cell carcinoma). RESULTS: At the median follow-up of 33 months, median
      survival (MS) and PFS were 29.1 and 15.7 months, respectively. p53 Pro/Pro was
      strongly associated with shorter survival in the entire cohort (MS of 11.8 versus
      29.1 months, P < 0.0001; adjusted hazard ratio for death, 2.05; 95% confidence
      interval, 1.30-3.24; P = 0.002 for Pro/Pro versus Arg/Arg). MDM2 G/G was
      associated with markedly reduced survival in squamous cell carcinoma (MS of 10.3
      versus 49.4 months; adjusted hazard ratio for death, 7.9; 95% confidence
      interval, 2.4-26.0; P = 0.0007 for G/G versus T/T) but not in adenocarcinoma (SNP
      histology interaction P = 0.004). CONCLUSIONS: In a large prospective cohort, p53
      Arg72Pro Pro/Pro was associated with a 2-fold increased risk of death in all
      esophageal cancers, whereas MDM2 T309G G/G was associated with a 7-fold increased
      risk of death in squamous cell carcinoma.

PMID- 19383812
TI  - Utility of p16 immunohistochemistry for the identification of Lynch syndrome.
AB  - PURPOSE: Immunohistochemistry for mismatch repair proteins has shown utility in
      the identification of Lynch syndrome, but majority of tumors with loss of MLH1
      expression are due to sporadic hypermethylation of the MLH1 promoter. These
      tumors can also show epigenetic silencing of other genes, such as p16. The aim of
      our study is to evaluate the utility of p16 immunohistochemistry in the
      prediction of MLH1 germline mutations. EXPERIMENTAL DESIGN: p16
      immunohistochemistry was appropriately evaluated in 79 colorectal cancers with
      loss of MLH1 expression. Methylation of MLH1 and p16 were quantitatively studied
      using real-time PCR assay Methylight. BRAF V600E mutation in tumor tissue was
      also investigated. Genetic testing for germline mutation of MLH1 was made on 52
      patients. RESULTS: Loss of p16 expression was seen in 21 of 79 samples (26.6%).
      There was found statistically significant association between p16 expression and
      p16 methylation (P < 0.001), MLH1 methylation (P < 0.001), and BRAF mutation (P <
      0.005). All tumors with loss of p16 expression showed hypermethylation of p16 (21
      of 21), 95.2% (20 of 21) showed MLH1 methylation, and 71.4% (15 of 21) were
      mutated for BRAF V600E. Mutational analysis showed pathogenic germline mutations
      in 8 of the patients, harboring 10 tumors. All 10 of these tumors showed normal
      staining of p16 in the immunochemical analysis. CONCLUSIONS: p16
      immunohistochemistry is a good surrogate marker for p16 and MLH1 epigenetic
      silencing due to hypermethylation, and is useful as screening tool in the
      selection of patients for genetic testing in Lynch syndrome.

PMID- 19383813
TI  - Combining simvastatin with the farnesyltransferase inhibitor tipifarnib results
      in an enhanced cytotoxic effect in a subset of primary CD34+ acute myeloid
      leukemia samples.
AB  - PURPOSE: To show whether the inhibitory effects of the cholesterol synthesis
      inhibitor simvastatin on human CD34(+) acute myeloid leukemia (AML) cells can be
      further promoted by combining it with the farnesyltransferase inhibitor
      tipifarnib. EXPERIMENTAL DESIGN: Normal CD34(+), AML CD34(+), and CD34(-) sorted
      subfractions, and AML cell lines (TF-1 and KG1A) were exposed to simvastatin and
      tipifarnib. RESULTS: Both simvastatin and tipifarnib showed a cytotoxic effect on
      AML cell lines, which was additive when used in combination. In primary sorted
      CD34(+) AML cells, a heterogeneous response pattern was observed upon treatment
      with simvastatin when analyzing cell survival. A group of normal (n = 12) and
      abnormal (n = 10) responders were identified within the AML CD34(+) subfraction
      when compared with normal CD34(+) cells. This distinction was not observed within
      the AML CD34(-) cell fraction. When the CD34(+) AML cells were exposed to
      simvastatin and tipifarnib, a significant enhanced inhibitory effect was shown
      exclusively in the normal AML responder group, whereas the AML CD34(-) cell
      fractions all showed an enhanced inhibitory effect. The observed heterogeneity in
      AML responsiveness could not be explained by differences in effects on
      cholesterol metabolism genes or extracellular signal-regulated kinase
      phosphorylation in response to simvastatin and tipifarnib treatment. CONCLUSION:
      The results suggest that combined treatment with statins and farnesyltransferase
      inhibitors may be beneficial for a subset of AML patients that can be defined by
      studying the AML CD34(+) fraction.

PMID- 19383814
TI  - A phase I, pharmacokinetic and pharmacodynamic study on vorinostat in combination
      with 5-fluorouracil, leucovorin, and oxaliplatin in patients with refractory
      colorectal cancer.
AB  - PURPOSE: We conducted a phase I study to determine the maximum tolerated dose of
      vorinostat in combination with fixed doses of 5-fluorouracil (FU), leucovorin,
      and oxaliplatin (FOLFOX). EXPERIMENTAL DESIGN: Vorinostat was given orally twice
      daily for 1 week every 2 weeks. FOLFOX was given on days 4 and 5 of vorinostat.
      The vorinostat starting dose was 100 mg twice daily. Escalation occurred in
      cohorts of three to six patients. Pharmacokinetics of vorinostat, FU, and
      oxaliplatin were studied. RESULTS: Twenty-one patients were enrolled.
      Thrombocytopenia, neutropenia, gastrointestinal toxicities, and fatigue increased
      in frequency and severity at higher dose levels of vorinostat. Two of 4 evaluable
      patients at dose level 4 (vorinostat 400 mg orally twice daily) developed dose
      limiting fatigue. One of 10 evaluable patients at dose level 3 (vorinostat 300 mg
      orally twice daily) had dose-limiting fatigue, anorexia, and dehydration. There
      were significant relationships between vorinostat dose and the area under the
      curve on days 1 and 5 (Pearson, < 0.001). The vorinostat area under the curve
      increased (P = 0.005) and clearance decreased (P = 0.003) on day 5 compared with
      day 1. The median C(max) of FU at each dose level increased significantly with
      increasing doses of vorinostat, suggesting a pharmacokinetic interaction between
      FU and vorinostat. Vorinostat-induced thymidylate synthase (TS) modulation was
      not consistent; only two of six patients had a decrease in intratumoral TS
      expression by reverse transcription-PCR. CONCLUSIONS: The maximum tolerated dose
      of vorinostat in combination with FOLFOX is 300 mg orally twice daily x 1 week
      every 2 weeks. Alternative vorinostat dosing schedules may be needed for optimal
      down-regulation of TS expression.

PMID- 19383815
TI  - Functionally overlapping roles of Abcg2 (Bcrp1) and Abcc2 (Mrp2) in the
      elimination of methotrexate and its main toxic metabolite 7-hydroxymethotrexate
      in vivo.
AB  - PURPOSE: ABCC2 (MRP2) and ABCG2 (BCRP) transport various endogenous and exogenous
      compounds, including many anticancer drugs, into bile, feces, and urine. We
      investigated the possibly overlapping roles of Abcg2 and Abcc2 in the elimination
      of the anticancer drug methotrexate (MTX) and its toxic metabolite 7
      hydroxymethotrexate (7OH-MTX). EXPERIMENTAL DESIGN: We generated and
      characterized Abcc2;Abcg2(-/-) mice, and used these to determine the overlapping
      roles of Abcc2 and Abcg2 in the elimination of MTX and 7OH-MTX after i.v.
      administration of 50 mg/kg MTX. RESULTS: Compared with wild-type, the plasma
      areas under the curve (AUC) for MTX were 1.6-fold and 2.0-fold higher in Abcg2(-/
      ) and Abcc2(-/-) mice, respectively, and 3.3-fold increased in Abcc2;Abcg2(-/-)
      mice. The biliary excretion of MTX was 23-fold reduced in Abcc2;Abcg2(-/-) mice,
      and the MTX levels in the small intestine were dramatically decreased. Plasma
      levels of 7OH-MTX were not significantly altered in Abcg2(-/-) mice, but the
      areas under the curve were 6.2-fold and even 12.4-fold increased in Abcc2(-/-)
      and Abcc2;Abcg2(-/-) mice, respectively. This indicates that Abcc2 compensates
      for Abcg2 deficiency but that Abcg2 can only partly compensate for Abcc2 absence.
      Furthermore, 21-fold decreased biliary 7OH-MTX excretion in Abcc2;Abcg2(-/-) mice
      and substantial 7OH-MTX accumulation in the liver and kidney were seen. We
      additionally found that in the absence of Abcc2, Abcg2 mediated substantial
      urinary excretion of MTX and 7OH-MTX. CONCLUSIONS: Abcc2 and Abcg2 together are
      major determinants of MTX and 7OH-MTX pharmacokinetics. Variations in ABCC2
      and/or ABCG2 activity due to polymorphisms or coadministered inhibitors may
      therefore substantially affect the therapeutic efficacy and toxicity in patients
      treated with MTX.

PMID- 19383816
TI  - Rectal mucosal microvascular blood supply increase is associated with colonic
      neoplasia.
AB  - PURPOSE: Endoscopic examination has proven effective in both detecting and
      preventing colorectal cancer; however, only about a quarter of eligible patients
      undergo screening. Even if the compliance rate increased, limited endoscopic
      capacity and cost would be prohibitive. There is a need for an accurate method to
      target colonoscopy to those most at risk of harboring colonic neoplasia.
      Exploiting field carcinogenesis seems to be a promising avenue. Our group
      recently reported that an early increase in blood supply (EIBS) is a reliable
      marker of field carcinogenesis in experimental models. We now investigate whether
      in situ detection of EIBS in the rectum can predict neoplasia elsewhere in the
      colon. EXPERIMENTAL DESIGN: We developed a novel polarization-gated spectroscopy
      fiber-optic probe that allows depth-selective interrogation of microvascular
      blood content. Using the probe, we examined the blood content in vivo from the
      rectal mucosa of 216 patients undergoing screening colonoscopy. RESULTS:
      Microvascular blood content was increased by approximately 50% in the
      endoscopically normal rectal mucosa of patients harboring advanced adenomas when
      compared with neoplasia-free patients irrespective of lesion location.
      Demographic factors and nonneoplastic lesions did not confound this observation.
      Logistic regression using mucosal oxyhemoglobin concentration and patient age
      resulted in a sensitivity of 83%, a specificity of 82%, and an area under the
      receiver operating characteristic curve of 0.88 for the detection of advanced
      adenomas. CONCLUSIONS: Increased microvascular blood supply in the normal rectal
      mucosa is associated with the presence of clinically significant neoplasia
      elsewhere in the colon, supporting the development of rectal EIBS as a colon
      cancer risk-stratification tool.

PMID- 19383817
TI  - Phase I study of MG98, an oligonucleotide antisense inhibitor of human DNA
      methyltransferase 1, given as a 7-day infusion in patients with advanced solid
      tumors.
AB  - PURPOSE: To assess the safety and tolerability, pharmacokinetics, and early
      evidence of antitumor activity of escalating doses of MG98, an antisense
      oligonucleotide to DNA methyltransferase 1 (DNMT1), which has been shown to
      reduce CpG island methylation and allow reexpression of tumor suppressor genes in
      vitro. EXPERIMENTAL DESIGN: In this phase I, open-label study, patients with
      advanced solid malignancies were treated with escalating doses of MG98
      administered as a continuous i.v. infusion over 7 days repeated every 14 days.
      Cohorts of three patients, which could be expanded to six patients, were studied.
      The maximum tolerated dose was defined as the highest dose at which no more than
      33% of subjects experienced dose-limiting toxicity. Pharmacokinetic and
      pharmacodynamic parameters of MG98 were also characterized. RESULTS: Thirty-three
      patients were treated at doses of 100 to 250 mg/m(2)/d MG98. MG98 was well
      tolerated with mild fatigue and myalgia, dose-limiting toxicity was asymptomatic
      transaminitis, and the maximum tolerated dose was 200 mg/m(2)/d. One patient
      achieved a partial response and another prolonged disease stabilization. Plasma
      half-life of MG98 was short (2 hours), drug concentrations reaching a dose
      dependent steady state during infusion with a volume of distribution equivalent
      to plasma volume. Suppression of DNMT1 expression was observed in 26 of 32
      patients studied. CONCLUSIONS: MG98 was well tolerated with early evidence of
      clinical activity. Proof of mechanism was observed and measurement of DNMT1
      expression in peripheral blood mononuclear cells may be useful in future phase II
      development.

PMID- 19383818
TI  - Phosphatidylinositol-3-kinase as a therapeutic target in melanoma.
AB  - PURPOSE: Phosphatidylinositol-3 kinases (PI3K) are critical for malignant
      cellular processes including growth, proliferation, and survival, and are targets
      of drugs in clinical development. We assessed expression of PI3K in melanomas and
      nevi, and studied associations between PI3K pathway members and in vitro response
      to a PI3K inhibitor, LY294002. EXPERIMENTAL DESIGN: Using Automated Quantitative
      Analysis, we quantified expression of p85 and p110alpha subunits in 540 nevi and
      523 melanomas. We determined the IC(50) for LY294002 for 11 melanoma cell lines
      and, using reverse phase protein arrays, assessed the association between levels
      of PI3K pathway members and sensitivity to LY294002. RESULTS: p85 and p110alpha
      tend to be coexpressed (P < 0.0001); expression was higher in melanomas than nevi
      (P < 0.0001) for both subunits, and higher in metastatic than primary melanomas
      for p85 (P < 0.0001). Although phospho-Akt (pAkt) levels decreased in all cell
      lines treated with LY294002, sensitivity was variable. We found no association by
      t tests between baseline p85, p110alpha, and pAkt levels and sensitivity to
      LY294002, whereas pS6 Ser(235) and Ser(240) were lower in the more resistant cell
      lines (P = 0.01 and P = 0.004, respectively). CONCLUSIONS: Expression of p85 and
      p110alpha subunits is up-regulated in melanoma, indicating that PI3K is a good
      drug target. Pretreatment pS6 levels correlated with sensitivity to the PI3K
      inhibitor, LY294002, whereas PI3K and pAkt did not, suggesting that full
      activation of the PI3K pathway is needed for sensitivity to PI3K inhibition. pS6
      should be evaluated as a predictor of response in melanoma patients treated with
      PI3K inhibitors, as these drugs enter clinical trials.

PMID- 19383819
TI  - Helicobacter pylori infection induces genetic instability of nuclear and
      mitochondrial DNA in gastric cells.
AB  - PURPOSE: Helicobacter pylori is a major cause of gastric carcinoma. To
      investigate a possible link between bacterial infection and genetic instability
      of the host genome, we examined the effect of H. pylori infection on known
      cellular repair pathways in vitro and in vivo. Moreover, various types of genetic
      instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined.
      EXPERIMENTAL DESIGN: We observed the effects of H. pylori infection on a gastric
      cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In
      AGS cells, the effect of H. pylori infection on base excision repair and mismatch
      repair (MMR) was analyzed by reverse transcription-PCR, Western blot, and
      activity assays. In mice, MMR expression was analyzed by reverse transcription
      PCR and the CA repeat instabilities were examined by Mutation Detection
      Enhancement gel electrophoresis. Mutation spectra in AGS cells and chronic
      gastritis tissue were determined by PCR, single-stranded conformation
      polymorphism, and sequencing. H. pylori vacA and cagA genotyping was determined
      by multiplex PCR and reverse hybridization. RESULTS: Following H. pylori
      infection, the activity and expression of base excision repair and MMR are down
      regulated both in vitro and in vivo. Moreover, H. pylori induces genomic
      instability in nuclear CA repeats in mice and in mtDNA of AGS cells and chronic
      gastritis tissue, and this effect in mtDNA is associated with bacterial
      virulence. CONCLUSIONS: Our results suggest that H. pylori impairs central DNA
      repair mechanisms, inducing a transient mutator phenotype, rendering gastric
      epithelial cells vulnerable to the accumulation of genetic instability and thus
      contributing to gastric carcinogenesis in infected individuals.

PMID- 19383820
TI  - Antitumor activity of GSK1904529A, a small-molecule inhibitor of the insulin-like
      growth factor-I receptor tyrosine kinase.
AB  - PURPOSE: Dysregulation of the insulin-like growth factor-I receptor (IGF-IR)
      signaling pathway has been implicated in the development of many types of tumors,
      including prostate, colon, breast, pancreatic, ovarian, and sarcomas. Agents that
      inhibit IGF-IR activity may be useful in treatment of patients with various
      cancers. EXPERIMENTAL DESIGN: Kinase assays were used to identify a selective
      small-molecule inhibitor of IGF-IR activity. The effects of this compound on IGF
      IR signaling, cell proliferation, and the cell cycle were determined using a
      panel of cell lines. Antitumor activity was evaluated in human tumor xenografts
      growing in athymic mice. Inhibition of IGF-IR and the closely related insulin
      receptor (IR) was measured in vivo, and the effect on glucose metabolism was
      evaluated. RESULTS: GSK1904529A selectively inhibits IGF-IR and IR with IC(50)s
      of 27 and 25 nmol/L, respectively. GSK1904529A blocks receptor
      autophosphorylation and downstream signaling, leading to cell cycle arrest. It
      inhibits the proliferation of cell lines derived from solid and hematologic
      malignancies, with multiple myeloma and Ewing's sarcoma cell lines being most
      sensitive. Oral administration of GSK1904529A decreases the growth of human tumor
      xenografts in mice, consistent with a reduction of IGF-IR phosphorylation in
      tumors. Despite the potent inhibitory activity of GSK1904529A on IR in vitro and
      in vivo, minimal effects on blood glucose levels are observed in animals at doses
      that show significant antitumor activity. CONCLUSION: GSK1904529A is a promising
      candidate for therapeutic use in IGF-IR-dependent tumors.

PMID- 19383822
TI  - Involvement of a novel chemokine decoy receptor CCX-CKR in breast cancer growth,
      metastasis and patient survival.
AB  - PURPOSE: The biological axes of chemokines and chemokine receptors, such as
      CXCR4/CXCL12, CCR7/CCL19 (CCL21), CCR9/CCL25, and CXCR5/CXCL13, are involved in
      cancer growth and metastasis. This study is aimed at the potential regulatory
      role of atypical chemokine binder CCX-CKR, as a scavenger of CCL19, CCL21, CCL25,
      and CXCL13, in human breast cancer. EXPERIMENTAL DESIGN: The role of CCX-CKR in
      human breast cancer was investigated in cell lines, animal models, and clinical
      samples. RESULTS: Overexpression of CCX-CKR inhibited cancer cell proliferation
      and invasion in vitro and attenuated xenograft tumor growth and lung metastasis
      in vivo. CCX-CKR can be regulated by cytokines such as interleukin-1beta, tumor
      necrosis factor-alpha, and IFN-gamma. Lack or low expression of CCX-CKR
      correlated with a poor survival rate in the breast cancer patients. A significant
      correlation between CCX-CKR and lymph node metastasis was observed in human
      breast cancer tissues. CCX-CKR status was an independent prognostic factor for
      disease-free survival in breast cancer patients. CONCLUSION: We showed for the
      first time that CCX-CKR is a negative regulator of growth and metastasis in
      breast cancer mainly by sequestration of homeostatic chemokines and subsequent
      inhibition of intratumoral neovascularity. This finding may lead to a new
      therapeutic strategy against breast cancer.

PMID- 19383821
TI  - Estrous cycle modulates ovarian carcinoma growth.
AB  - PURPOSE: The effects of reproductive hormones on ovarian cancer growth are not
      well understood. Here, we examined the effects of estrous cycle variation and
      specific reproductive hormones on ovarian cancer growth. EXPERIMENTAL DESIGN: We
      investigated the role of reproductive hormones in ovarian cancer growth using
      both in vivo and in vitro models of tumor growth. RESULTS: In vivo experiments
      using the HeyA8 and SKOV3ip1 ovarian cancer models showed that tumor cell
      inoculation during proestrus significantly increased tumor burden (251-273%)
      compared with injection during the estrus phase. Treatment of ovariectomized mice
      with 17beta-estradiol resulted in a 404% to 483% increase in tumor growth
      compared with controls. Progestins had no significant effect, but did block
      estrogen-stimulated tumor growth. Tumors collected from mice sacrificed during
      proestrus showed increased levels of vascular endothelial growth factor (VEGF)
      and microvessel density compared with mice injected during estrus. HeyA8,
      SKOV3ip1, and mouse endothelial (MOEC) cells expressed estrogen receptor alpha
      and beta and progesterone receptor at the protein and mRNA levels, whereas 2774
      ovarian cancer cells were estrogen receptor-negative. In vitro assays showed that
      17beta-estradiol significantly increased ovarian cancer cell adhesion to collagen
      in estrogen receptor-positive, but not in estrogen receptor-negative cells.
      Additionally, 17beta-estradiol increased the migratory potential of MOEC cells,
      which was abrogated by the mitogen-activated protein kinase (MAPK) inhibitor, PD
      09859. Treatment with 17beta-estradiol activated MAPK in MOEC cells, but not in
      HeyA8 or SKOV3ip1 cells. CONCLUSION: Our data suggest that estrogen may promote
      in vivo ovarian cancer growth, both directly and indirectly, by making the tumor
      microenvironment more conducive for cancer growth.

PMID- 19383823
TI  - BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and
      broad antitumor activity.
AB  - PURPOSE: Antimitotic chemotherapy remains a cornerstone of multimodality
      treatment for locally advanced and metastatic cancers. To identify novel mitosis
      specific agents with higher selectivity than approved tubulin-binding agents
      (taxanes, Vinca alkaloids), we have generated inhibitors of Polo-like kinase 1, a
      target that functions predominantly in mitosis. EXPERIMENTAL DESIGN: The first
      compound in this series, suitable for i.v. administration, has entered clinical
      development. To fully explore the potential of Polo-like kinase 1 inhibition in
      oncology, we have profiled additional compounds and now describe a novel clinical
      candidate. RESULTS: BI 6727 is a highly potent (enzyme IC(50) = 0.87 nmol/L,
      EC(50) = 11-37 nmol/L on a panel of cancer cell lines) and selective
      dihydropteridinone with distinct properties. First, BI 6727 has a pharmacokinetic
      profile favoring sustained exposure of tumor tissues with a high volume of
      distribution and a long terminal half-life in mice (V(ss) = 7.6 L/kg, t(1/2) = 46
      h) and rats (V(ss) = 22 L/kg, t(1/2) = 54 h). Second, BI 6727 has physicochemical
      and pharmacokinetic properties that allow in vivo testing of i.v. as well as oral
      formulations, adding flexibility to dosing schedules. Finally, BI 6727 shows
      marked antitumor activity in multiple cancer models, including a model of taxane
      resistant colorectal cancer. With oral and i.v. routes of administration, the
      total weekly dose of BI 6727 is most relevant for efficacy, supporting the use of
      a variety of well-tolerated dosing schedules. CONCLUSION: These findings warrant
      further investigation of BI 6727 as a tailored antimitotic agent; clinical
      studies have been initiated.

PMID- 19383824
TI  - Mutations in the hepatitis C virus core gene are associated with advanced liver
      disease and hepatocellular carcinoma.
AB  - PURPOSE: Hepatitis C virus (HCV) infection can promote the development of
      hepatocellular carcinoma (HCC). Published data implicate the HCV core gene in
      oncogenesis. We tested the hypothesis that core gene sequences from HCC patients
      differ from those of patients without cirrhosis/HCC. EXPERIMENTAL DESIGN: Full
      length HCV sequences from HCC patients and controls were obtained from the
      investigators and GenBank and compared with each other. A logistic regression
      model was developed to predict the HCC risk of individual point mutations and
      other sequence features. Mutations in partial sequences (bases 36-288) from HCC
      patients and controls were also analyzed. The first base of the AUG start codon
      was designated position 1. RESULTS: A logistic regression model developed through
      analysis of full-length core gene sequences identified seven polymorphisms
      significantly associated with increased HCC risk (36G/C, 209A, 271U/C, 309A/C,
      435A/C, 481A, and 546A/C) and an interaction term (for 209A-271U/C) that had an
      odds ratio <1.0. Three of these polymorphisms could be analyzed in the partial
      sequences. Two of them, 36G/C and 209A, were again associated with increased HCC
      risk, but 271U/C was not. The odds ratio of 209A-271U/C was not significant.
      CONCLUSIONS: HCV core genes from patients with and without HCC differ at several
      positions. Of interest, 209A has been associated with IFN resistance and HCC in
      previous studies. Our findings suggest that HCV core gene sequence data might
      provide useful information about HCC risk. Prospective investigation is needed to
      establish the temporal relationship between appearance of the viral mutations and
      development of HCC.

PMID- 19383825
TI  - Protein acetylation and histone deacetylase expression associated with malignant
      breast cancer progression.
AB  - PURPOSE: Excess histone deacetylase (HDAC) activity can induce hypoacetylation of
      histone and nonhistone protein substrates, altering gene expression patterns and
      cell behavior potentially associated with malignant transformation. However, HDAC
      expression and protein acetylation have not been studied in the context of breast
      cancer progression. EXPERIMENTAL DESIGN: We assessed expression levels of
      acetylated histone H4 (ac-H4), ac-H4K12, ac-tubulin, HDAC1, HDAC2, and HDAC6 in
      22 reduction mammoplasties and in 58 specimens with synchronous normal
      epithelium, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC)
      components. Differences among groups were tested for significance using
      nonparametric tests. RESULTS: From normal epithelium to DCIS, there was a marked
      reduction in histone acetylation (P < 0.0001). Most cases showed similar levels
      of acetylation in DCIS and IDC, although some showed further reduction of ac-H4
      and ac-H4K12 from DCIS to IDC. Expression of HDAC1, HDAC2, and HDAC6 was also
      significantly reduced but by a smaller magnitude. Greater reductions of H4
      acetylation and HDAC1 levels were observed from normal to DCIS in estrogen
      receptor-negative compared with estrogen receptor-positive, and in high-grade
      compared with non-high-grade tumors. CONCLUSION: Overall, there was a global
      pattern of hypoacetylation associated with progression from normal to DCIS to
      IDC. These findings suggest that the reversal of this hypoacetylation in DCIS and
      IDC could be an early measure of HDAC inhibitor activity.

PMID- 19383826
TI  - Identification and metastatic potential of tumor-initiating cells in malignant
      rhabdoid tumor of the kidney.
AB  - PURPOSE: Malignant rhabdoid tumor of the kidney (MRTK) is a rare and highly
      aggressive malignancy of infanthood. In an effort to delineate MRTK progression,
      we investigated the metastatic fate of some MRTK cells using xenotransplantation
      animal models and the tumor-initiating potential of CD133(+) MRTK cells.
      EXPERIMENTAL DESIGN: We established two MRTK cell lines (JMU-RTK-1 and JMU-RTK-2)
      from patients with MRTK. We generated five luciferase-expressing MRTK cells for
      in vivo luminescent imaging and evaluated the metastatic fate in an orthotopic
      xenotransplantation model. Capacities of MRTK-initiating cells were examined in
      nonobese diabetic/severe combined immunodeficient mice after antibody-mediated
      magnetic bead sorting. Use of chemokine receptor CXCR4 expression as a metastatic
      marker was evaluated by flow cytometry and Western blotting. RESULTS: MRTK cell
      lines showed distant organ metastasis. JMU-RTK-1, JMU-RTK-2, and G401 cells
      showed considerable aggressiveness compared with SWT-1 and SWT-2 cells (P <
      0.05). Moreover, as few as 1,000 CD133(+) MRTK cells initiated tumor development
      in nonobese diabetic/severe combined immunodeficient mice by 21 days (60-100%) in
      all examined cell lines, although the same number of CD133(-) MRTK cells could
      not form tumors (0%). Interestingly, the metastatic potential of the CD133(+)
      population remained unaffected compared with a nonenriched population. The
      potential metastatic marker CXCR4 was expressed in CD133(+) and CD133(-) MRTK
      cells, and CD133(-) cells seemed to play a cooperative role in terms of
      tumorigenicity and metastasis. CONCLUSIONS: These results suggest that CD133(+)
      cells may determine the metastatic fate of MRTK cells and that CD133(-) cells may
      play an auxiliary role in tumor progression and metastasis.

PMID- 19383827
TI  - Administration of glucocorticoids to ovarian cancer patients is associated with
      expression of the anti-apoptotic genes SGK1 and MKP1/DUSP1 in ovarian tissues.
AB  - PURPOSE: To prevent chemotherapy-related side effects, synthetic glucocorticoids,
      for example, dexamethasone, are routinely administered to patients with ovarian
      cancer. However, preclinical data implicate glucocorticoids in suppressing
      chemotherapy-mediated apoptosis in epithelial tumors. The anti-apoptotic
      mechanisms underlying this increased survival have been shown to require up
      regulation of prosurvival genes, including serum and glucocorticoid-regulated
      kinase 1 (SGK1) and map kinase phosphatase 1 (MKP1)/dual specificity phosphatase
      1 (DUSP1). Despite abundant preclinical data, there are no correlative studies in
      patients. We therefore evaluated anti-apoptotic gene expression in tumor samples
      from patients randomized to dexamethasone or normal saline. EXPERIMENTAL DESIGN:
      Eighteen patients were randomized before exploratory laparotomy for suspected
      ovarian cancer. Dexamethasone or normal saline was administered i.v. following
      anesthesia. Ovarian and omental tumor samples were collected intra-operatively
      before and after infusion. Samples were analyzed for histology and glucocorticoid
      receptor expression by immunohistochemistry. SGK1 and MKP1/DUSP1 mRNA levels were
      determined using quantitative real-time PCR. RESULTS: Ten patients were
      evaluable. At 30 min postinfusion, tumor samples from five patients receiving
      dexamethasone revealed an average SGK1 mRNA induction of 6.1-fold (SEM, +/-2.6)
      compared with only 1.5-fold (SEM, +/-0.4) in tumor samples from five patients
      receiving normal saline (P = 0.028). Average MKP1/DUSP1 mRNA expression was
      increased by 8.2-fold (SEM, +/-2.9) following dexamethasone versus 1.1-fold (SEM,
      +/-0.4) following normal saline (P = 0.009). All samples expressed glucocorticoid
      receptor. CONCLUSION: Glucocorticoid administration to patients is associated
      with rapid up-regulation of SGK1 and MKP1 expression in ovarian tumors. This
      finding supports the hypothesis that pharmacologic doses of glucocorticoids may
      decrease chemotherapy effectiveness in ovarian cancer patients through increased
      anti-apoptotic gene expression.

PMID- 19383828
TI  - LYRIC/AEG-1 is targeted to different subcellular compartments by ubiquitinylation
      and intrinsic nuclear localization signals.
AB  - PURPOSE: LYRIC/AEG-1 has been reported to influence breast cancer survival and
      metastases, and its altered expression has been found in a number of cancers. The
      cellular function of LYRIC/AEG-1 has previously been related to its subcellular
      distribution in cell lines. LYRIC/AEG-1 contains three uncharacterized nuclear
      localization signals (NLS), which may regulate its distribution and, ultimately,
      function in cells. EXPERIMENTAL DESIGN: Immunohistochemistry of a human prostate
      tissue microarray composed of 179 prostate cancer and 24 benign samples was used
      to assess LYRIC/AEG-1 distribution. Green fluorescent protein-NLS fusion proteins
      and deletion constructs were used to show the ability of LYRIC/AEG-1 NLS to
      target green fluorescent protein from the cytoplasm to the nucleus.
      Immunoprecipitation and Western blotting were used to show posttranslational
      modification of LYRIC/AEG-1 NLS regions. RESULTS: Using a prostate tissue
      microarray, significant changes in the distribution of LYRIC/AEG-1 were observed
      in prostate cancer as an increased cytoplasmic distribution in tumors compared
      with benign tissue. These differences were most marked in high grade and
      aggressive prostate cancers and were associated with decreased survival. The COOH
      terminal extended NLS-3 (amino acids 546-582) is the predominant regulator of
      nuclear localization, whereas extended NLS-1 (amino acids 78-130) regulates its
      nucleolar localization. Within the extended NLS-2 region (amino acids 415-486),
      LYRIC/AEG-1 can be modified by ubiquitin almost exclusively within the cytoplasm.
      CONCLUSIONS: Changes in LYRIC/AEG-1 subcellular distribution can predict Gleason
      grade and survival. Two lysine-rich regions (NLS-1 and NLS-3) can target
      LYRIC/AEG-1 to subcellular compartments whereas NLS-2 is modified by ubiquitin in
      the cytoplasm.

PMID- 19383830
TI  - Molecular genetics of medullary thyroid carcinoma: the quest for novel
      therapeutic targets.
AB  - Medullary thyroid carcinoma (MTC) is a rare tumour arising from neural crest
      derived parafollicular C-cells. Metastatic MTC patients are incurable because the
      cancer does not respond to radiotherapy or chemotherapy. The REarranged during
      Transfection (RET) proto-oncogene plays a key role in the development of MTC.
      However, one-half of the sporadic MTC do not carry RET mutations. Mice models and
      early evidence obtained in human samples suggest that other genes, including
      those encoding components of the RB1 (retinoblastoma) and TP53 tumour-suppressor
      pathways, may be involved in MTC formation. Here, we review the data on the
      involvement of genes acting in the RET and RB1/TP53 pathways in MTC.
      Understanding genetic lesions that occur in MTC is a prerequisite to identifying
      molecular therapeutic targets in MTC and in improving the efficacy of RET
      targeted therapies.

PMID- 19383829
TI  - IRF4: Immunity. Malignancy! Therapy?
AB  - IRF4, a member of the Interferon Regulatory Factor (IRF) family of transcription
      factors, is expressed in cells of the immune system, where it transduces signals
      from various receptors to activate or repress gene expression. IRF4 expression is
      a key regulator of several steps in lymphoid-, myeloid-, and dendritic-cell
      differentiation, including the differentiation of mature B cells into antibody
      secreting plasma cells. IRF4 expression is also associated with many lymphoid
      malignancies, with recent evidence pointing to an essential role in multiple
      myeloma, a malignancy of plasma cells. Interference with IRF4 expression is
      lethal to multiple myeloma cells, irrespective of their genetic etiology, making
      IRF4 an "Achilles' heel" that may be exploited therapeutically.

PMID- 19383831
TI  - Brain regions underlying word finding difficulties in temporal lobe epilepsy.
AB  - Word finding difficulties are often reported by epileptic patients with seizures
      originating from the language dominant cerebral hemisphere, for example, in
      temporal lobe epilepsy. Evidence regarding the brain regions underlying this
      deficit comes from studies of peri-operative electro-cortical stimulation, as
      well as post-surgical performance. This evidence has highlighted a role for the
      anterior part of the dominant temporal lobe in oral word production. These
      conclusions contrast with findings from activation studies involving healthy
      speakers or acute ischaemic stroke patients, where the region most directly
      related to word retrieval appears to be the posterior part of the left temporal
      lobe. To clarify the neural basis of word retrieval in temporal lobe epilepsy, we
      tested forty-three drug-resistant temporal lobe epilepsy patients (28 left, 15
      right). Comprehensive neuropsychological and language assessments were performed.
      Single spoken word production was elicited with picture or definition stimuli.
      Detailed analysis allowed the distinction of impaired word retrieval from other
      possible causes of naming failure. Finally, the neural substrate of the deficit
      was assessed by correlating word retrieval performance and resting-state brain
      metabolism in 18 fluoro-2-deoxy-d-glucose-Positron Emission Tomography. Naming
      difficulties often resulted from genuine word retrieval failures (anomic states),
      both in picture and in definition tasks. Left temporal lobe epilepsy patients
      showed considerably worse performance than right temporal lobe epilepsy patients.
      Performance was poorer in the definition than in the picture task. Across
      patients and the left temporal lobe epilepsy subgroup, frequency of anomic state
      was negatively correlated with resting-state brain metabolism in left posterior
      and basal temporal regions (Brodmann's area 20-37-39). These results show the
      involvement of posterior temporal regions, within a larger antero-posterior-basal
      temporal network, in the specific process of word retrieval in temporal lobe
      epilepsy. A tentative explanation for these findings is that epilepsy induces
      functional deafferentation between anterior temporal structures devoted to
      semantic processing and neocortical posterior temporal structures devoted to
      lexical processing.

PMID- 19383832
TI  - The effect of N-acetyl-aspartyl-glutamate and N-acetyl-aspartate on white matter
      oligodendrocytes.
AB  - Elevations of the levels of N-acetyl-aspartyl-glutamate (NAAG) and N-acetyl
      aspartate (NAA) are associated with myelin loss in the leucodystrophies Canavan's
      disease and Pelizaeus-Merzbacher-like disease. NAAG and NAA can activate and
      antagonize neuronal N-methyl-D-aspartate (NMDA) receptors, and also act on group
      II metabotropic glutamate receptors. Oligodendrocytes and their precursors have
      recently been shown to express NMDA receptors, and activation of these receptors
      in ischaemia leads to the death of oligodendrocyte precursors and the loss of
      myelin. This raises the possibility that the failure to develop myelin, or
      demyelination, occurring in the leucodystrophies could reflect an action of NAAG
      or NAA on oligodendrocyte NMDA receptors. However, since the putative subunit
      composition of NMDA receptors on oligodendrocytes differs from that of neuronal
      NMDA receptors, the effects of NAAG and NAA on them are unknown. We show that
      NAAG, but not NAA, evokes an inward membrane current in cerebellar white matter
      oligodendrocytes, which is reduced by NMDA receptor block (but not by block of
      metabotropic glutamate receptors). The size of the current evoked by NAAG,
      relative to that evoked by NMDA, was much smaller in oligodendrocytes than in
      neurons, and NAAG induced a rise in [Ca(2+)](i) in neurons but not in
      oligodendrocytes. These differences in the effect of NAAG on oligodendrocytes and
      neurons may reflect the aforementioned difference in receptor subunit
      composition. In addition, as a major part of the response in oligodendrocytes was
      blocked by tetrodotoxin (TTX), much of the NAAG-evoked current in
      oligodendrocytes is a secondary consequence of activating neuronal NMDA
      receptors. Six hours exposure to 1 mM NAAG did not lead to the death of cells in
      the white matter. We conclude that an action of NAAG on oligodendrocyte NMDA
      receptors is unlikely to be a major contributor to white matter damage in the
      leucodystrophies.

PMID- 19383833
TI  - Eradication of microorganisms embedded in biofilm by an ethanol-based catheter
      lock solution.
AB  - BACKGROUND: Interdialytic locking of catheters with antimicrobial agents is
      frequently used for preventing catheter-related infections, often associated with
      biofilm formation. We determined the bactericidal effect of 60% ethanol (ETOH)
      versus a 46.7% trisodium citrate (TSC) solution on biofilm embedded in silicone
      catheters. METHODS: Four- and 24-h biofilms of Staphylococcus aureus, S.
      epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans
      established in a microfermentor were exposed to ETOH and TSC for up to 24 h and
      the number of remaining viable microorganisms was determined. RESULTS: ETOH 60%
      was significantly more effective than 46.7% TSC in rapidly eradicating sessile
      cells from all microorganisms tested. A 20-min ETOH 60% treatment completely
      eradicated the Gram-negative bacilli and C. albicans biofilms, which initially
      contained up to 10(8) and 10(5) cells, respectively. Gram-positive cocci biofilms
      only showed a significant 2.6-4.3 log reduction in the initial viable counts
      after 20 min of ETOH 60% treatment, with eradication occurring after 30 min.
      Confocal laser scanning microscopy observation of ETOH-treated biofilm showed
      sparse cells with respiratory activity. TSC 46.7% eradicated none of the tested
      microorganisms. In contrast, ETOH 60% totally eradicated planktonic cells,
      whereas TSC had significant bactericidal activity against K. pneumoniae, P.
      aeruginosa and C. albicans after 20 min, 1 and 24 h, respectively, but none on
      the Staphylococcus species. CONCLUSIONS: This in vitro study demonstrates the
      superior antimicrobial activity of ETOH 60% in contrast to TSC 46.7% in
      eradicating biofilm formed on a silicon catheter. Hence, ethanol-based solution
      shows promise as a catheter lock solution.

PMID- 19383834
TI  - Patients' representations of their end-stage renal disease: relation with
      mortality.
AB  - BACKGROUND: Self-regulation theory explains how patients' illness perceptions
      influence self-management behaviour (e.g. via adherence to treatment). Following
      these assumptions, we explored whether illness perceptions of ESRD-patients are
      related to mortality rates. METHODS: Illness perceptions of 182 patients
      participating in the NECOSAD-2 study in the period between December 2004 and June
      2005 were assessed. Cox proportional hazard models were used to estimate whether
      subsequent all-cause mortality could be attributed to illness perception
      dimensions. RESULTS: One-third of the participants had died at the end of the
      follow-up. Mortality rates were higher among patients who believed that their
      treatment was less effective in controlling their disease (perceived treatment
      control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for
      sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If
      we consider risk factors for mortality, we tend to rely on clinical parameters
      rather than on patients' representations of their illness. Nevertheless, results
      from the current exploration may suggest that addressing patients' personal
      beliefs regarding the effectiveness of treatment can provide a powerful tool for
      predicting and perhaps even enhancing survival.

PMID- 19383835
TI  - Transplantation in type 1 diabetes.

PMID- 19383836
TI  - Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC
      transporter ABCC11 gene determine earwax type?
AB  - One single-nucleotide polymorphism (SNP), 538G>A (Gly180Arg), in the ABCC11 gene
      determines the type of earwax. The G/G and G/A genotypes correspond to the wet
      type of earwax, whereas A/A corresponds to the dry type. Wide ethnic differences
      exist in the frequencies of those alleles, reflecting global migratory waves of
      the ancestors of humankind. We herein provide the evidence that this genetic
      polymorphism has an effect on the N-linked glycosylation of ABCC11, intracellular
      sorting, and proteasomal degradation of the variant protein. Immunohistochemical
      studies with cerumen gland-containing tissue specimens revealed that the ABCC11
      WT protein was localized in intracellular granules and large vacuoles, as well as
      at the luminal membrane of secretory cells in the cerumen gland, whereas granular
      or vacuolar localization was not detected for the SNP (Arg180) variant. This SNP
      variant lacking N-linked glycosylation is recognized as a misfolded protein in
      the endoplasmic reticulum and readily undergoes ubiquitination and proteasomal
      degradation, which determines the dry type of earwax as a mendelian trait with a
      recessive phenotype. For rapid genetic diagnosis of axillary osmidrosis and
      potential risk of breast cancer, we developed specific primers for the SmartAmp
      method that enabled us to clinically genotype the ABCC11 gene within 30 min.

PMID- 19383837
TI  - Mothers of children with special health care needs: documenting the experience of
      their children's care in the school setting.
AB  - The numbers of children with special health care needs (CSHCN) have increased in
      schools. This study was conducted to document mothers' experiences of the care
      their CSHCN receive across health care and educational settings. Data were
      collected during standardized, open-ended, one-on-one interviews with 10 mothers
      of CSHCN in urban, suburban, and rural areas in a Midwestern state. Interviews
      were transcribed and content analysis revealed five themes: (a) communication,
      (b) educational system issues, (c) mother as a caregiver and expert, (d)
      navigating the system, and (e) strategies and coping. Describing and
      understanding experiences of mothers of CSHCN is important to developing
      appropriate supportive interventions.

PMID- 19383838
TI  - Part 1--factors associated with school nurse ratios: an analysis of state data.
AB  - Despite the recognized importance of school nurses, the ratios of nurse to pupil
      are insufficient in many states across the country. The purpose of this study was
      to describe school nurse-to-pupil ratios by state and to statistically identify
      factors that may influence these ratios. Funding per pupil unit in general and
      support services and laws mandating school nurse ratios were some of the factors
      found to be associated with school ratios. Although the study has significant
      limitations, this is the first study of its kind to examine factors associated
      with ratios using secondary databases that are state-specific. Data such as this
      provide a context for studying those factors potentially influencing ratios.
      Further studies are needed to explore the numerous potential determinants
      described in the literature. Once key factors are identified, school nurses can
      effectively focus their efforts to lower school nurse-pupil ratios.

PMID- 19383839
TI  - Aqueous Extract of Shi-Liu-Wei-Liu-Qi-Yin Induces G2/M Phase Arrest and Apoptosis
      in Human Bladder Carcinoma Cells via Fas and Mitochondrial Pathway.
AB  - Shi-Liu-Wei-Liu-Qi-Yin (SLWLQY) was traditionally used to treat cancers. However,
      scientific evidence of the anticancer effects still remains undefined. In this
      study, we aimed to clarify the possible mechanisms of SLWLQY in treating cancer.
      We evaluated the effects of SLWLQY on apoptosis-related experiments inducing in
      TSGH-8301 cells by (i) 3-(4,5-dimethylthiazol-zyl)-2,5-diphenylterazolium bromide
      (MTT) for cytotoxicity; (ii) cell-cycle analysis and (iii) western blot analysis
      of the G2/M-phase and apoptosis regulatory proteins. Human bladder carcinoma TSGH
      8301 cells were transplanted into BALB/c nude mice as a tumor model for
      evaluating the antitumor effect of SLWLQY. Treatment of SLWLQY resulted in the
      G2/M phase arrest and apoptotic death in a dose-dependent manner, accompanied by
      a decrease in cyclin-dependent kinases (cdc2) and cyclins (cyclin B1). SLWLQY
      stimulated increases in the protein expression of Fas and FasL, and induced the
      cleavage of caspase-3, caspase-9 and caspase-8. The ratio of Bax/Bcl(2) was
      increased by SLWLQY treatment. SLWLQY markedly reduced tumor size in TSGH-8301
      cells-xenografted tumor tissues. In the tissue specimen, SLWLQY up-regulated the
      expression of Fas, FasL and Bax proteins, and down-regulated Bcl(2) as well as in
      in vitro assay. Our results showed that SLWLQY reduced tumor growth, caused cell
      cycle arrest and apoptosis in TSGH-8301 cells via the Fas and mitochondrial
      pathway.

PMID- 19383840
TI  - Lyprinol-is it a useful anti-inflammatory agent?
AB  - The New Zealand green lipped mussel preparation Lyprinol is available without a
      prescription from a supermarket, pharmacy or Web. The Food and Drug
      Administration have recently warned Lyprinol USA about their extravagant anti
      inflammatory claims for Lyprinol appearing on the web. These claims are put to
      thorough review. Lyprinol does have anti-inflammatory mechanisms, and has anti
      inflammatory effects in some animal models of inflammation. Lyprinol may have
      benefits in dogs with arthritis. There are design problems with the clinical
      trials of Lyprinol in humans as an anti-inflammatory agent in osteoarthritis and
      rheumatoid arthritis, making it difficult to give a definite answer to how
      effective Lyprinol is in these conditions, but any benefit is small. Lyprinol
      also has a small benefit in atopic allergy. As anti-inflammatory agents, there is
      little to choose between Lyprinol and fish oil. No adverse effects have been
      reported with Lyprinol. Thus, although it is difficult to conclude whether
      Lyprinol does much good, it can be concluded that Lyprinol probably does no major
      harm.

PMID- 19383841
TI  - The social construction of "evidence-based'' drug prevention programs: a
      reanalysis of data from the Drug Abuse Resistance Education (DARE) program.
AB  - This study explores the possibility that any drug prevention program might be
      considered ;;evidence-based'' given the use of data analysis procedures that
      optimize the chance of producing statistically significant results by reanalyzing
      data from a Drug Abuse Resistance Education (DARE) program evaluation. The
      analysis produced a number of statistically significant differences between the
      DARE and control conditions on alcohol and marijuana use measures. Many of these
      differences occurred at cutoff points on the assessment scales for which post hoc
      meaningful labels were created. Our results are compared to those from
      evaluations of programs that appear on evidence-based drug prevention lists.

PMID- 19383842
TI  - Mental well-being and subjective health of 11- to 15-year-old boys and girls in
      Scotland, 1994-2006.
AB  - BACKGROUND: Promoting young people's mental well-being and reducing socioeconomic
      inequalities are priority areas for WHO and the Scottish Government. This article
      describes changes in the subjective health and mental well-being of adolescents
      living in Scotland between 1994 and 2006, and investigates socioeconomic
      inequalities in mental well-being and subjective health over time. METHODS: Data
      from the 1994, 1998, 2002 and 2006 Health Behaviour in School-aged Children
      surveys were analysed using Multilevel Binomial modelling. RESULTS: Boys and
      younger adolescents scored more favourably on measures of confidence, happiness,
      helplessness and feeling left out than girls and older adolescents. Multiple
      health complaints (MHC) were also more prevalent among girls than boys.
      Significant increases over time were observed for all mental well-being measures
      among girls and for all but confidence among boys. Similarly, there was a
      significant decrease in odds of MHC over time for both boys and girls. There were
      no socioeconomic inequalities in any of the five outcomes in 1998. However by
      2006, socioeconomic inequalities in young people's happiness, confidence and MHC
      emerged, while inequalities in girls' helplessness also approached significance.
      Between 1998 and 2006 significant increases in socioeconomic inequalities in
      happiness and MHC were observed and increases in feeling left out also approached
      significance. CONCLUSIONS: Adolescent mental well-being and subjective health in
      Scotland is improving. However, gender differences persist and socioeconomic
      inequalities are emerging for some measures, suggesting that a longer term
      monitoring of mental well-being and subjective health in Scotland is required.

PMID- 19383843
TI  - An Ariadne's thread to the identification and annotation of noncoding RNAs in
      eukaryotes.
AB  - Non-protein coding RNAs (ncRNAs) have emerged as a vast and heterogeneous portion
      of eukaryotic transcriptomes. Several ncRNA families, either short (<200
      nucleotides, nt) or long (>200 nt), have been described and implicated in a
      variety of biological processes, from translation to gene expression regulation
      and nuclear trafficking. Most probably, other families are still to be
      discovered. Computational methods for ncRNA research require different approaches
      from the ones normally used in the prediction of protein-coding genes. Indeed,
      primary sequence alone is often insufficient to infer ncRNA functionality,
      whereas secondary structure and local conservation of portions of the transcript
      could provide useful information for both the prediction and the functional
      annotation of ncRNAs. Here we present an overview of computational methods and
      bioinformatics resources currently available for studying ncRNA genes,
      introducing the common themes as well as the different approaches required for
      long and short ncRNA identification and annotation.

PMID- 19383844
TI  - ImmunoGrid, an integrative environment for large-scale simulation of the immune
      system for vaccine discovery, design and optimization.
AB  - Vaccine research is a combinatorial science requiring computational analysis of
      vaccine components, formulations and optimization. We have developed a framework
      that combines computational tools for the study of immune function and vaccine
      development. This framework, named ImmunoGrid combines conceptual models of the
      immune system, models of antigen processing and presentation, system-level models
      of the immune system, Grid computing, and database technology to facilitate
      discovery, formulation and optimization of vaccines. ImmunoGrid modules share
      common conceptual models and ontologies. The ImmunoGrid portal offers access to
      educational simulators where previously defined cases can be displayed, and to
      research simulators that allow the development of new, or tuning of existing,
      computational models. The portal is accessible at <igrid
      ext.cryst.bbk.ac.uk/immunogrid>.

PMID- 19383845
TI  - Epigenetic reversal of acquired resistance to 5-fluorouracil treatment.
AB  - Acquired and intrinsic resistance still remains a limitation to the clinical use
      of 5-fluorouracil (5-FU). The contribution of epigenetic changes to the
      development of drug resistance remains to be elucidated. Several genes that are
      hypermethylated and silenced have been identified in colorectal cancer. Based on
      the findings described in the accompanying article, we hypothesized that acquired
      resistance to "pulse" 5-FU has an epigenetic origin and might be reversed. Here,
      we present a novel therapeutic approach to circumvent clinical resistance to
      bolus 5-FU, that is, treatment of bolus 5-FU-resistant colorectal cancer cells
      with low-dose 5-azadeoxycytidine (DAC), an inhibitor of DNA hypermethylation,
      restored sensitivity to 5-FU as well as 5-fluorouridine. Moreover, treatment of
      nude mice bearing a 5-FU-resistant tumor, characterized by decreased levels of
      UMP kinase (UMPK), with DAC overcame resistance to bolus 5-FU. DAC-mediated
      restoration of 5-FU sensitivity was associated with increases in UMPK levels. An
      increase in UMPK protein and mRNA levels following treatment with low-dose DAC
      was observed in cultured bolus 5-FU-resistant colorectal cancer cells (HCT-8) and
      in mice bearing these tumors. We conclude that DAC-mediated restoration of
      sensitivity to bolus 5-FU is mediated at least in part by increased UMPK levels
      and clinical resistance to 5-FU due to decreased UMPK in colorectal cancer may be
      overcome by including methylation inhibitors such as DAC.

PMID- 19383847
TI  - Decreased levels of UMP kinase as a mechanism of fluoropyrimidine resistance.
AB  - 5-Fluorouracil (5-FU) continues to be widely used for treatment of
      gastrointestinal cancers. Because many tumors show primary or acquired
      resistance, it is important to understand the molecular basis underlying the
      mechanism of resistance to 5-FU. In addition to its effect on thymidylate
      synthase inhibition and DNA synthesis, 5-FU may also influence RNA metabolism.
      Our previous studies revealed that colorectal cancer cells resistant to bolus 5
      FU (HCT-8/4hFU) showed significantly decreased incorporation of the drug into
      RNA. Resistance to bolus 5-FU was associated with lower expression of UMP kinase
      (UMPK), an enzyme that plays an important role in the activation of 5-FU to 5
      FUTP and its incorporation into RNA. Activities of other 5-FU-metabolizing
      enzymes (e.g., thymidine kinase, uridine phosphorylase, thymidine phosphorylase,
      and orotate phosphoribosyltransferase) remained unchanged between sensitive and
      resistant cell lines. Herein, we show that UMPK down-regulation in 5-FU-sensitive
      cells (HCT-8/P) induces resistance to bolus 5-FU treatment. Moreover, HCT-8/4hFU
      cells are even more cross-resistant to treatment with 5-fluorouridine, consistent
      with the current understanding of 5-fluorouridine as a RNA-directed drug.
      Importantly, colorectal cancer hepatic metastases isolated from patients
      clinically resistant to weekly bolus 5-FU/leucovorin treatment exhibited
      decreased mRNA expression of UMPK but not thymidylate synthase or
      dihydropyrimidine dehydrogenase compared with tumor samples of patients not
      previously exposed to 5-FU. Our findings provide new insights into the mechanisms
      of acquired resistance to 5-FU in colorectal cancer and implicate UMPK as an
      important mechanism of clinical resistance to pulse 5-FU treatment in some
      patients.

PMID- 19383846
TI  - The indenoisoquinoline noncamptothecin topoisomerase I inhibitors: update and
      perspectives.
AB  - Because camptothecins are effective against previously resistant tumors and are
      the only class of topoisomerase I (Top1) inhibitors approved for cancer
      treatment, we developed the indenoisoquinolines. Like camptothecins, the
      indenoisoquinolines selectively trap Top1-DNA cleavage complexes and have been
      cocrystallized with the Top1-DNA cleavage complexes. Indenoisoquinolines show
      antitumor activity in animal models. They have several advantages over the
      camptothecins: (a) They are synthetic and chemically stable. (b) The Top1
      cleavage sites trapped by the indenoisoquinolines have different genomic
      locations, implying differential targeting of cancer cell genomes. (c) The Top1
      cleavage complexes trapped by indenoisoquinolines are more stable, indicative of
      prolonged drug action. (d) They are seldom or not used as substrates for the
      multidrug resistance efflux pumps (ABCG2 and MDR-1). Among the >400
      indenoisoquinolines synthesized and evaluated, three have been retained as leads
      for clinical development by the National Cancer Institute: NSC 706744, NSC 725776
      (Indimitecan), and NSC 724998 (Indotecan). The trapping of Top1 cleavage
      complexes by indenoisoquinolines in cells results in the rapid and sustained
      phosphorylation of histone H2AX (gamma-H2AX). We discuss the use of gamma-H2AX as
      a pharmacodynamic biomarker for the clinical development of the
      indenoisoquinolines.

PMID- 19383848
TI  - Takashi Tsuruo.

PMID- 19383849
TI  - Dehydrocostuslactone disrupts signal transducers and activators of transcription
      3 through up-regulation of suppressor of cytokine signaling in breast cancer
      cells.
AB  - This study investigates the anticancer effect of dehydrocostuslactone (DHE), a
      plant-derived sesquiterpene lactone, on human breast cancer cells. DHE inhibits
      cell proliferation by inducing cells to undergo cell cycle arrest and apoptosis.
      DHE suppresses the expression of cyclin D, cyclin A, cyclin-dependent kinase 2,
      and cdc25A and increases the amount of p53 and p21, resulting in G(0)/G(1)-S
      phase arrest in MCF-7 cells. In contrast, DHE caused S-G(2)/M arrest by
      increasing p21 expression and chk1 activation and inhibiting cyclin A, cyclin B,
      cdc25A, and cdc25C expression in MDA-MB-231 cells. DHE induces up-regulation of
      Bax and Bad, down-regulation of Bcl-2 and Bcl-XL, and nuclear relocation of the
      mitochondrial factors apoptosis-inducing factor and endonuclease G. We also found
      that DHE inhibits survival signaling through the Janus tyrosine kinase-signal
      transducer and activator of transcription-3 signaling by increasing the
      expression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3. Reduction of
      SOCS-1 and SOCS-3 expression by small interfering RNA inhibits DHE-mediated
      signal transducer and activator of transcription-3 inhibition, p21 up-regulation,
      and cyclin-dependent kinase 2 blockade, supporting the hypothesis that DHE
      inhibits cell cycle progression and cell death through SOCS-1 and SOCS-3.
      Significantly, animal studies have revealed a 50% reduction in tumor volume after
      a 45-day treatment period. Taken together, this study provides new insights into
      the molecular mechanism of the DHE action that may contribute to the
      chemoprevention of breast cancer.

PMID- 19383850
TI  - Bortezomib induces schedule-dependent modulation of gemcitabine pharmacokinetics
      and pharmacodynamics in non-small cell lung cancer and blood mononuclear cells.
AB  - Bortezomib combination with gemcitabine/cisplatin in patients with advanced
      tumors, predominantly non-small cell lung cancer (NSCLC), showed an unexpected
      transient drop in the deoxycytidine plasma levels, a marker for gemcitabine
      activity. This study investigates the pharmacokinetic/pharmacodynamic effect of
      bortezomib on gemcitabine in NSCLC and peripheral blood mononuclear cells (PBMC).
      Gemcitabine metabolites, including difluoro-dCTP (dFdCTP), were studied in PBMCs
      from bortezomib/gemcitabine/cisplatin-treated patients and from volunteers and
      NSCLC cells (H460 and SW1573) exposed to 4 h simultaneous or sequential
      treatments of gemcitabine (50 MUmol/L, 4 h) and bortezomib (100 nmol/L, 2 h).
      Gemcitabine total phosphate levels measured by liquid chromatography-tandem mass
      spectrometry in PBMCs from bortezomib/gemcitabine/cisplatin-treated patients were
      strongly reduced after 90 min (-82.2%) up to 4 h post-gemcitabine infusion
      compared with gemcitabine/cisplatin-treated patients. Accordingly,
      bortezomib/gemcitabine combinations reduced dFdCTP in PBMCs treated ex vivo.
      Surprisingly, differential effects were observed in NSCLC cells. dFdCTP decreased
      after 4 h following gemcitabine removal in H460 but continued to increase for 24
      h in SW1573. However, dFdCTP significantly increased (2-fold) in both cell lines
      in the bortezomib -> gemcitabine exposure, coinciding with a major reduction in
      cell growth compared with single drugs, and the highest increase of deoxycytidine
      kinase expression, possibly mediated via E2F-1. Bortezomib affects differently
      gemcitabine pharmacokinetics/pharmacodynamics in PBMCs and NSCLC cells,
      suggesting that PBMCs are not adequate to evaluate the anticancer activity of
      bortezomib/gemcitabine combinations. The bortezomib -> gemcitabine/cisplatin
      schedule appeared a safe and active combination for the treatment of advanced
      NSCLC and the bortezomib -> gemcitabine was the most cytotoxic combination in
      NSCLC cells. The increase of deoxycytidine kinase and dFdCTP might contribute to
      this synergistic interaction and supports its further clinical investigation.

PMID- 19383851
TI  - Thymidylate synthase gene variations: predictive and prognostic markers.
AB  - Since its introduction more than 50 years ago by Heidelberger et al., the
      fluoropyrimidine 5-fluorouracil (5-FU) has remained the mainstay of therapeutic
      regimens used in the treatment of colorectal cancer and other human malignancies,
      with single-agent response rates of 20% to 25% in advanced disease stage.
      Pharmacogenomics has emerged as a useful tool to address interindividual gene
      variations by analyzing the interplay of host and tumor genotype and drug
      efficacy and toxicity. Having a reliable panel of prognostic and predictive
      markers will be critical in selecting an individualized and tailored chemotherapy
      regimen based on the particular tumor and host genotype. Although conflicting
      results have been reported, higher thymidylate synthase (TS) protein and mRNA
      expression levels in tumors have generally been associated with poor clinical
      outcome in patients treated with 5-FU-based chemotherapy regimens. However, the
      cause of the variability in TS expression still remains not fully understood,
      although several germ-line polymorphisms seem to affect the expression of TS,
      some of which have been found to have an effect on prognosis and the probability
      of response to 5-FU-based chemotherapy. This review will provide an update on
      pharmacogenomic studies of TS that were aimed at elucidating their role as
      prognostic and predictive markers.

PMID- 19383852
TI  - Heidelberger symposium on the 50th anniversary of fluoropyrimidines.

PMID- 19383853
TI  - Two types of human malignant melanoma cell lines revealed by expression patterns
      of mitochondrial and survival-apoptosis genes: implications for malignant
      melanoma therapy.
AB  - Human malignant melanoma has poor prognosis because of resistance to apoptosis
      and therapy. We describe identification of the expression profile of 1,037
      mitochondria-focused genes and 84 survival-apoptosis genes in 21 malignant
      melanoma cell lines and 3 normal melanocyte controls using recently developed
      hMitChip3 cDNA microarrays. Unsupervised hierarchical clustering analysis of
      1,037 informative genes, and 84 survival-apoptosis genes, classified these
      malignant melanoma cell lines into type A (n = 12) and type B (n = 9). Three
      hundred fifty-five of 1,037 (34.2%) genes displayed significant (P <= 0.030;
      false discovery rate <= 3.68%) differences (+/- >= 2.0-fold) in average
      expression, with 197 genes higher and 158 genes lower in type A than in type B.
      Of 84 genes with known survival-apoptosis functions, 38 (45.2%) displayed the
      significant (P < 0.001; false discovery rate < 0.15%) difference. Antiapoptotic
      (BCL2, BCL2A1, PPARD, and RAF1), antioxidant (MT3, PRDX5, PRDX3, GPX4, GLRX2, and
      GSR), and proapoptotic (BAD, BNIP1, APAF1, BNIP3L, CASP7, CYCS, CASP1, and VDAC1)
      genes expressed at higher levels in type A than in type B, whereas the different
      set of antiapoptotic (PSEN1, PPP2CA, API5, PPP2R1B, PPP2R1A, and FIS1),
      antioxidant (HSPD1, GSS, SOD1, ATOX1, and CAT), and proapoptotic (ENDOG, BAK1,
      CASP2, CASP4, PDCD5, HTRA2, SEPT4, TNFSF10, and PRODH) genes expressed at lower
      levels in type A than in type B. Microarray data were validated by quantitative
      reverse transcription-PCR. These results showed the presence of two types of
      malignant melanoma, each with a specific set of dysregulated survival-apoptosis
      genes, which may prove useful for development of new molecular targets for
      therapeutic intervention and novel diagnostic biomarkers for treatment and
      prognosis of malignant melanoma.

PMID- 19383855
TI  - Research and advocacy in nutrition therapy: our specialty needs you.

PMID- 19383854
TI  - The role of floxuridine in metastatic liver disease.
AB  - Liver metastases are mainly supplied by the hepatic artery. Sustained high levels
      of intratumoral drug are achievable with certain drugs given via the hepatic
      artery. Floxuridine (FUDR) is an ideal drug for hepatic arterial infusion (HAI)
      due to its short half life, steep dose response curve, high total body clearance,
      and high hepatic extraction. HAI FUDR has consistently shown higher response
      rates than systemic chemotherapy alone, and some studies have shown a survival
      advantage. HAI FUDR in combination with systemic chemotherapy has evolved over
      the years and may be used in palliative, neoadjuvant, and adjuvant settings. The
      dramatic responses observed with HAI FUDR plus modern era systemic chemotherapy
      offer the possibility of resection and cure in selected patients. The high
      hepatic extraction of FUDR limits systemic side effects. Toxicity includes
      biliary and gastrointestinal ulcers.

PMID- 19383856
TI  - Large calcified intra-abdominal mass in a newborn.

PMID- 19383857
TI  - Relation of exhaled nitric oxide levels to development of bronchopulmonary
      dysplasia.
AB  - OBJECTIVE: To test the hypothesis that exhaled nitric oxide levels on day 28 and
      changes in exhaled nitric oxide levels in the neonatal period would differ
      according to whether infants developed bronchopulmonary dysplasia (BPD) and its
      severity. DESIGN: Prospective observational study. SETTING: Tertiary neonatal
      intensive care unit. PATIENTS: 80 infants (median gestational age 28, range 24-32
      weeks), 46 of whom developed BPD. INTERVENTIONS: Exhaled nitric oxide
      measurements were attempted on days 3, 5, 7, 14, 21 and 28. MAIN OUTCOME
      MEASURES: BPD (oxygen dependency at 28 days), mild BPD (oxygen dependent at 28
      days, but not 36 weeks postmenstrual age (PMA)); moderate BPD (oxygen dependent
      at 36 weeks PMA) and severe BPD (respiratory support dependent at 36 weeks PMA).
      RESULTS: On day 28, exhaled nitric oxide levels were higher in infants with BPD
      compared to those without BPD (p<0.001) and there was a linear trend in exhaled
      nitric oxide results as BPD severity increased (p = 0.006). No significances in
      the change in exhaled nitric oxide levels over the neonatal period were found
      between the four groups. CONCLUSION: Exhaled nitric oxide levels are raised in
      infants with established BPD, particularly in those developing moderate or severe
      BPD, and may reflect ongoing inflammation.

PMID- 19383858
TI  - Dr Clement Smith (1901-1988) of Boston, pioneer of modern neonatal medicine.
AB  - Clinician, physiologist and teacher, Smith may be justly regarded as the father
      of modern neonatal medicine. He also appreciated the importance of prenatal
      medicine.

PMID- 19383859
TI  - Improving survival for infants of <26 weeks' gestation, 1995-2005.

PMID- 19383860
TI  - Red cell transport and transfusion in preterm infants.

PMID- 19383861
TI  - Reduced levels of antimicrobial proteins and peptides in human cord blood plasma.

PMID- 19383862
TI  - The extremely preterm births in Florence.

PMID- 19383863
TI  - Sonographic findings in premature infants with necrotising enterocolitis.

PMID- 19383864
TI  - Giving vancomycin as a continuous infusion.

PMID- 19383865
TI  - Benchmarking neonatal anthropometric charts published in the last decade.

PMID- 19383866
TI  - MRI elucidates unusual cranial mass.

PMID- 19383867
TI  - Recurrent diabetic ketoacidosis in an adolescent.

PMID- 19383868
TI  - The rights of Indigenous children around the world - still far from a reality.

PMID- 19383869
TI  - One-year survival in congenital diaphragmatic hernia, 1995-2006.

PMID- 19383871
TI  - Actions of fibroblast growth factor-8 in bone cells in vitro.
AB  - The fibroblast growth factors (FGFs) are a group of at least 25 structurally
      related peptides that are involved in many biological processes. Some FGFs are
      active in bone, including FGF-1, FGF-2, and FGF-18, and recent evidence indicates
      that FGF-8 is osteogenic, particularly in mesenchymal stem cells. In the current
      study, we found that FGF-8 was expressed in rat primary osteoblasts and in
      osteoblastic UMR-106 and MC3T3-E1 cells. Both FGF-8a and FGF-8b potently
      stimulated the proliferation of osteoblastic cells, whereas they inhibited the
      formation of mineralized bone nodules in long-term cultures of osteoblasts and
      reduced the levels of osteoblast differentiation markers, osteocalcin, and bone
      sialoprotein. FGF-8a induced the phosphorylation of p42/p44 mitogen-activated
      protein kinase (MAPK) in osteoblastic cells; however, its mitogenic actions were
      not blocked by either the MAPK kinase (MEK) inhibitor U-0126 or the PI 3-kinase
      (PI3K) inhibitor LY-294002. Interestingly, FGF-8a, unlike FGF-8b and other
      members of the family, inhibited osteoclastogenesis in mouse bone marrow
      cultures, and this was via a receptor activator of NF-kappaB ligand
      (RANKL)/osteoprotegerin (OPG)-independent manner. However, FGF-8a did not affect
      osteoclastogenesis in RAW 264.7 cells (a macrophage cell line devoid of stromal
      cells) exogenously stimulated by RANKL, nor did it affect mature osteoclast
      function as assessed in rat calvarial organ cultures and isolated mature
      osteoclasts. In summary, we have demonstrated that FGF-8 is active in bone cells,
      stimulating osteoblast proliferation in a MAPK-independent pathway and inhibiting
      osteoclastogenesis via a RANKL/OPG-independent mechanism. These data suggest that
      FGF-8 may have a physiological role in bone acting in an autocrine/paracrine
      manner.

PMID- 19383872
TI  - Effects of 7 days of exercise training on insulin sensitivity and responsiveness
      in type 2 diabetes mellitus.
AB  - The objectives of this study were to determine whether 1) the improvement in
      insulin action induced by short-term exercise training in patients with type 2
      diabetes is due to an improvement in insulin sensitivity, an improvement in
      insulin responsiveness, or a combination of improved insulin sensitivity and
      responsiveness and 2) short-term exercise training results in improved
      suppression of hepatic glucose production by insulin. Fourteen obese patients
      with type 2 diabetes, age 64 +/- 2 yr, underwent a two-stage hyperinsulinemic
      euglycemic clamp procedure, first stage 40 mU.m(-2).min(-1) insulin infusion,
      second stage 1,000 mU.m(-2).min(-1) insulin infusion, together with a [3
      (3)H]glucose infusion, before and after 7 days of exercise. The training
      consisted of 30 min of cycling and 30 min of treadmill walking at approximately
      70% of maximal aerobic capacity daily for 7 days. The exercise program resulted
      in improvements in insulin action in the absence of weight loss. Glucose disposal
      rates during the euglycemic clamp were significantly increased at both
      hyperinsulinemic stages after training (40 mU: 1.84 +/- 0.32 to 2.67 +/- 0.37
      mg.kg(-1).min(-1), P < 0.0001; 1,000 mU: 7.57 +/- 0.61 to 8.84 +/- 0.56 mg.kg(
      1).min(-1), P = 0.008). Hepatic glucose production, both in the basal state (3.17
      +/- 0.43 vs. 2.54 +/- 0.26 mg.kg(-1).min(-1), P = 0.05) and during the 40-mU
      clamp stage (1.15 +/- 0.41 vs. 0.46 +/- 0.20 mg.kg(-1).min(-1), P = 0.03), was
      significantly reduced after training. One week of vigorous exercise training can
      induce significant improvements in insulin action in type 2 diabetes. These
      improvements include increased peripheral insulin sensitivity and responsiveness
      as well as enhanced suppression of hepatic glucose production.

PMID- 19383873
TI  - Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements,
      and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells.
AB  - Fatty acids stimulate lipid accumulation in parallel with increased expression of
      adipose differentiation-related protein (ADRP) in liver cells. Although it is
      generally considered that the fatty acid effect on ADRP expression is mediated by
      peroxisome proliferator-activated receptors (PPARs), we identified here an
      additional molecular mechanism using the NMuLi mouse liver nonparenchymal cell
      line, which expresses PPARgamma and delta but not alpha. Oleic acid (OA) and
      specific ligands for PPARgamma and -delta stimulated ADRP expression as well as
      the -2,090-bp ADRP promoter activity which encompasses the PPAR response element
      (PPRE) adjacent to an Ets/activator protein (AP)-1 site. When the AP-1 site was
      mutated, OA failed to stimulate the activity despite the presence of the PPRE,
      whereas ligands for PPARgamma and -delta did stimulate it and so did a PPARalpha
      ligand under the coexpression of PPARalpha. DNA binding of AP-1 was stimulated by
      OA but not by PPAR ligands. Because we previously demonstrated that Pycnogenol
      (PYC), a French maritime pine bark extract, suppressed ADRP expression in
      macrophages partly by suppression of AP-1 activity, we tested the effect of PYC
      on NMuLi cells. PYC reduced the OA-induced ADRP expression along with suppression
      of lipid droplet formation. However, PYC neither suppressed the OA-stimulated
      ADRP promoter activity nor DNA binding of AP-1 but, instead, reduced the ADRP
      mRNA half-life. All these results indicate that the effect of OA on ADRP
      expression requires AP-1 as well as PPRE, and PYC suppresses the ADRP expression
      in part by facilitating mRNA degradation. PYC, a widely used dietary supplement,
      could be beneficial for the prevention of excessive lipid accumulation such as
      hepatic steatosis.

PMID- 19383874
TI  - Transcription factors in the development of medial hypothalamic structures.
AB  - The hypothalamus has historically been subdivided into nuclei, agglomerations of
      cell bodies that are visually distinct in histological sections. Regulatory
      functions of metabolism have been assigned to the various hypothalamic nuclei
      principally by analysis of animals with lesions of individual nuclei but also via
      various means of stimulation, such as cooling or heating probes. Biochemical and
      molecular specificity of these studies became possible with the identification
      and synthesis of neurotransmitters as well as the means to manipulate the
      expression of endogenous neurotransmitters and their receptors by genetic means .
      The arcuate nucleus (ARC) is likely to be the primary site for neurons that sense
      circulating fuels and energy reserves (POMC/CART neurons, NPY/AGRP neurons),
      whereas the paraventricular nucleus (PVN) receives input from the ARC and harbors
      many of the releasing factors (CRF, TRH, vasopressin, and oxytocin) that control
      pituitary hormone release. The ventromedial nucleus (VMN) receives input from the
      ARC and plays a critical role in energy balance in parallel with the ARC. The VMN
      and PVN also send descending projections to the autonomic nervous system and
      other pathways that control ingestive behavior and metabolism. Developmental
      analyses have revealed that the neurons that comprise the hypothalamic nuclei
      arise by differentiation and migration from stem cells within the ventricular
      zone. Based on recent work, it is becoming clear that coordination between
      numerous transcription factors that determine specification, survival, and
      migration is necessary for the formation of the hypothalamus, with each nucleus
      being determined by its own unique set of factors. In this minireview, we will
      provide a selective view of the roles that transcription factors play in the
      developing hypothalamus.

PMID- 19383876
TI  - Delinquency: risks and protective factors.

PMID- 19383875
TI  - Arginine vasopressin regulation in pre- and postpubertal male rats by the
      androgen metabolite 3beta-diol.
AB  - Arginine vasopressin (AVP) is a nonapeptide expressed in several brain regions.
      In addition to its well-characterized role in osmoregulation, AVP regulates
      paternal behavior, aggression,circadian rhythms, and the stress response. In the
      bed nucleus of the stria terminalis (BST), AVP gene expression is tightly
      regulated by gonadal steroid hormones. However, the degree by which AVP is
      regulated by gonadal steroid hormones in the suprachiasmatic nucleus (SCN) and
      medial amygdala (MeA) is unclear. Previous studies have shown that AVP expression
      in the brain of gonadectomized rats is restored with testosterone, 17beta
      estradiol, and 5alpha-dihydrotestosterone(DHT) replacement. In addition, we have
      demonstrated that 3beta-diol, a metabolite of DHT,increased AVP promoter activity
      in a neuronal cell line and that the effects of 3beta-diol on AVP promoter
      activity were mediated by estrogen receptor-beta. To test whether 3beta-diol has
      a physiological role in the regulation of central AVP expression in vivo, we
      gonadectomized pre- and postpubertal male rats and followed with once daily
      injections of estradiol benzoate (EB),DHT-propionate, 3beta-diol-dipropionate, or
      vehicle. The SCN, BST, and MeA were analyzed for AVP mRNA expression using in
      situ hybridization. In the BST, intact juveniles had significantly fewer AVP
      expressing cells than adults. GDX abolished all AVP mRNA expression in the BST in
      both age groups, whereas treatment with EB restored >80% and DHTP <10% of the AVP
      expression. Interestingly, 3beta-diol-proprionate was more effective at inducing
      AVP expression in juveniles than in adults, suggesting that the regulation of AVP
      by 3beta-diol might be age dependent [corrected].

PMID- 19383877
TI  - The ups and downs of thyrotropin-releasing hormone.

PMID- 19383878
TI  - The off-target effects of torcetrapib.

PMID- 19383879
TI  - Theoretical models of DNA topology simplification by type IIA DNA topoisomerases.
AB  - It was discovered 12 years ago that type IIA topoisomerases can simplify DNA
      topology--the steady-state fractions of knots and links created by the enzymes
      are many times lower than the corresponding equilibrium fractions. Though this
      property of the enzymes made clear biological sense, it was not clear how small
      enzymes could selectively change the topology of very large DNA molecules, since
      topology is a global property and cannot be determined by a local DNA-protein
      interaction. A few models, suggested to explain the phenomenon, are analyzed in
      this review. We also consider experimental data that both support and contravene
      these models.

PMID- 19383880
TI  - Genome-wide de novo prediction of cis-regulatory binding sites in prokaryotes.
AB  - Although cis-regulatory binding sites (CRBSs) are at least as important as the
      coding sequences in a genome, our general understanding of them in most sequenced
      genomes is very limited due to the lack of efficient and accurate experimental
      and computational methods for their characterization, which has largely hindered
      our understanding of many important biological processes. In this article, we
      describe a novel algorithm for genome-wide de novo prediction of CRBSs with high
      accuracy. We designed our algorithm to circumvent three identified difficulties
      for CRBS prediction using comparative genomics principles based on a new method
      for the selection of reference genomes, a new metric for measuring the similarity
      of CRBSs, and a new graph clustering procedure. When operon structures are
      correctly predicted, our algorithm can predict 81% of known individual binding
      sites belonging to 94% of known cis-regulatory motifs in the Escherichia coli K12
      genome, while achieving high prediction specificity. Our algorithm has also
      achieved similar prediction accuracy in the Bacillus subtilis genome, suggesting
      that it is very robust, and thus can be applied to any other sequenced
      prokaryotic genome. When compared with the prior state-of-the-art algorithms, our
      algorithm outperforms them in both prediction sensitivity and specificity.

PMID- 19383882
TI  - A randomized trial of a church-based diabetes self-management program for African
      Americans with type 2 diabetes.
AB  - PURPOSE: This study developed and tested a culturally appropriate, church-based
      intervention to improve diabetes self-management. Research Design and Methods
      This was a randomized trial conducted at 24 African American churches in central
      North Carolina. Churches were randomized to receive the special intervention (SI;
      13 churches, 117 participants) or the minimal intervention (MI; 11 churches, 84
      participants). The SI included an 8-month intensive phase, consisting of 1
      individual counseling visit, 12 group sessions, monthly phone contacts, and 3
      encouragement postcards, followed by a 4-month reinforcement phase including
      monthly phone contacts. The MI received standard educational pamphlets by mail.
      Outcomes were assessed at 8 and 12 months; the primary outcome was comparison of
      8-month A1C levels. RESULTS: At baseline, the mean age was 59 years, A1C 7.8%,
      and body mass index 35.0 kg/m(2); 64% of participants were female. For the 174
      (87%) participants returning for 8-month measures, mean A1C (adjusted for
      baseline and group randomization) was 7.4% for SI and 7.8% for MI, with a
      difference of 0.4% (95% confidence interval [CI], 0.1-0.6, P = .009). In a larger
      model adjusting for additional variables, the difference was 0.5% (95% CI, 0.2
      0.7, P < .001). At 12 months, the difference between groups was not significant.
      Diabetes knowledge and diabetes-related quality of life significantly improved in
      the SI group compared with the MI group. Among SI participants completing an
      acceptability questionnaire, intervention components and materials were rated as
      highly acceptable. CONCLUSIONS: The church-based intervention was well received
      by participants and improved short-term metabolic control.

PMID- 19383883
TI  - Relationship between epidemiologic risk factors and hormone receptor expression
      in ovarian cancer: results from the Nurses' Health Study.
AB  - Hormone receptor expression in tumors may offer etiologic information for ovarian
      cancer, particularly in light of known associations with hormonal and
      reproductive risk factors. Tissue microarrays constructed from 157 paraffin
      embedded blocks of epithelial ovarian tumors collected from participants in the
      Nurses' Health Study were stained for estrogen receptor-alpha (ERalpha) and
      progesterone receptor (PR). We examined receptor expression by invasion, grade,
      and histologic subtype. Multivariate unconditional logistic regression was used
      to evaluate whether hormonal, reproductive, and anthropometric risk factors were
      differentially associated with the risk of developing receptor-positive or
      receptor-negative ovarian tumors compared with controls. PR-expressing tumors
      were less likely to be invasive (P = 0.05) and more likely to be of a lower grade
      (P < 0.001) and stage (P = 0.007) compared with PR- tumors. ERalpha status was
      not associated with any pathologic features of the tumor (P > 0.34). Increasing
      age, being postmenopausal, and postmenopausal hormone use were associated with an
      increased risk of developing ERalpha+, but not ERalpha- (P(heterogeneity) =
      0.001, 0.06, and 0.06, respectively) and PR-, but not PR+, tumors
      (P(heterogeneity) = 0.08, 0.003, and 0.40, respectively), whereas height was only
      associated with the risk of developing PR- disease (P(heterogeneity) = 0.08).
      There were no clear risk differentials with OC use, parity, body mass index, or
      physical activity. Reproductive and hormonal risk factors are associated with
      subgroups of ovarian cancer defined by histologic subtype or ERalpha and PR
      status. These finding support specific models of hormone mediated triggers of
      ovarian cancer.

PMID- 19383884
TI  - Reproducibility of random periareolar fine needle aspiration in a multi
      institutional Cancer and Leukemia Group B (CALGB) cross-sectional study.
AB  - BACKGROUND: Random periareolar fine needle aspiration (RPFNA) is a research
      technique developed to assess short-term breast cancer risk in women at increased
      risk of breast cancer. Although there is increasing acceptance of RPFNA, neither
      the reproducibility nor the inter-institutional compatibility of RPFNA has been
      established. To address these key limitations, the Cancer and Leukemia Group B
      (CALGB) Prevention Group tested the reproducibility of RPFNA in a multi
      institutional cross-sectional study. METHODS: Sixty-three high-risk women from
      five CALGB institutions (Duke, Ohio State, Roswell Park, Dana Farber, and
      Vermont) underwent RPFNA from July 1, 2007 to June 30, 2008. Duplicate bilateral
      RPFNA was performed on each woman by a single investigator on a single day.
      Masood Cytology Index score was assessed by a single blinded cytopathologist.
      RESULTS: There was a high degree of statistical agreement in the Masood Cytology
      Index scores of duplicate RPFNA samples from the same breast, with a Spearman
      correlation coefficient of 0.8312 (P < 0.0001). Importantly, although there was
      agreement in duplicate samples from the same breast, there was lack of agreement
      between duplicate samples from the opposite breast. CONCLUSIONS: This multi
      institutional study shows that RPFNA is a highly reproducible measure of breast
      cytology in a cooperative group cross-sectional trial. RPFNA did not show a high
      degree of agreement between breasts, suggesting that breast cancer risk and
      progression may occur at different rates in individual breasts from a single
      woman. These studies provide proof-of-principle for future RPFNA-based
      cooperative group prevention studies.

PMID- 19383885
TI  - Physical activity as a determinant of fecal bile acid levels.
AB  - Physical activity is protective against colon cancer, whereas colonic bile acid
      exposure is a suspected risk factor. Although likely related, the association
      between physical activity and bile acid levels has not been well-studied.
      Furthermore, the effect of triglycerides, which are known to modify bile acid
      levels, on this relationship has not been investigated. We conducted a cross
      sectional analysis of baseline fecal bile acid levels for 735 colorectal adenoma
      formers obtained from participants in a phase III ursodeoxycholic acid
      chemoprevention trial. Compared with the lowest quartile of recreational physical
      activity duration, the highest quartile was associated with a 17% lower fecal
      bile acid concentration, adjusted for age, sex, dietary fiber intake, and body
      mass index (P = 0.042). Furthermore, consistent with a previously established
      relationship between serum triglyceride levels and bile acid metabolism, we
      stratified by triglyceride level and observed a 34% lower fecal bile acid
      concentration (highest versus lowest quartiles of physical activity) in
      individuals with low triglycerides (<136 mg/dL; P = 0.002). In contrast, no
      association between physical activity and fecal bile acid concentration was
      observed for subjects with high triglycerides (> or =136 mg/dL). Our results
      suggest that the biological mechanism responsible for the protective effect of
      physical activity on the incidence of colon cancer may be partially mediated by
      decreasing colonic bile acid exposure. However, this effect may be limited to
      individuals with lower triglyceride levels.

PMID- 19383886
TI  - Dietary acrylamide intake and brain cancer risk.
AB  - BACKGROUND: Acrylamide is a probable human carcinogen, which is present in
      several heat-treated foods. In epidemiologic studies, positive associations with
      endometrial, ovarian, and renal cell cancer risk have been observed. The
      incidence of central nervous system tumors was increased upon acrylamide
      administration in drinking water to rats. In the current study, the association
      between dietary acrylamide intake and human brain cancer risk was investigated
      for the first time. METHODS: In 1986, 120,852 persons (ages 55-69 years) were
      included in the Netherlands Cohort Study on diet and cancer. At baseline, a
      random subcohort of 5,000 participants was randomly selected from the total
      cohort for a case-cohort approach. Acrylamide intake was assessed with a food
      frequency questionnaire at baseline and based on acrylamide analyses in relevant
      Dutch foods. Hazard ratios (HR) were calculated using Cox proportional hazards
      analysis. Subgroup analyses were done for microscopically verified brain cancer,
      astrocytic gliomas, high-grade astrocytic gliomas, and never-smokers. The
      acrylamide risk estimates were adjusted for possible brain cancer risk factors.
      RESULTS: After 16.3 years of follow-up, 216 brain cancer cases were available for
      analysis. The multivariable-adjusted HR per 10 microg/d increment of acrylamide
      intake was 1.02 (95% confidence interval, 0.89-1.16). HRs were not significantly
      increased either when dietary acrylamide intake was analyzed as a categorical
      variable. Also, there was no association in the subgroups based on histology and
      smoking. CONCLUSION: In this prospective cohort study, acrylamide intake was not
      associated with brain cancer risk.

PMID- 19383887
TI  - Prospective study of JC virus seroreactivity and the development of colorectal
      cancers and adenomas.
AB  - BACKGROUND: Infection with JC virus has been proposed as a risk factor for
      colorectal cancer. A nested case-control study was conducted to evaluate the
      association between prediagnostic JC virus antibodies and the risk of incident
      colorectal cancer and adenomas. METHODS: Two research serum banks were
      established in Washington County, MD in 1974 and 1989, with the collection of
      blood samples from >45,000 volunteers. Incident colorectal cancer cases diagnosed
      through 2006 (n = 611) were identified among participants by linkage to
      population-based cancer registries, contributing 729 pairs of observations. Cases
      of adenomatous polyps (n = 123) were identified from participants of the 1989
      cohort who reported having a colonoscopy-detected adenoma at follow-up through
      2000 with histology confirmed through medical record review. One control was
      matched to each case on age, sex, race, and date of blood draw, and, for adenoma
      controls, date of endoscopy. IgG antibodies to JC virus were measured using virus
      like particle ELISA. Associations between JC virus seropositivity and colorectal
      cancer and adenomas were estimated using conditional logistic regression.
      RESULTS: Overall, there was no association between antibodies to JC virus and
      colorectal cancer [odds ratio (OR), 0.91; 95% confidence interval (95% CI), 0.71
      1.17]. However, a statistically significant positive association between JC virus
      seropositivity and subsequent adenoma diagnosis was observed among males (OR,
      2.31; 95% CI, 1.20-4.46), whereas a statistically significant inverse association
      was observed among females (OR, 0.31; 95% CI, 0.14-0.67; P for interaction =
      0.01), after adjustment for baseline smoking and body mass index. CONCLUSIONS:
      Overall, JC virus seropositivity was not associated with colorectal cancer
      development up to 31 years later. Future studies are needed to confirm the
      adenoma findings.

PMID- 19383888
TI  - HER-2/neu overexpression as a predictor for the transition from in situ to
      invasive breast cancer.
AB  - The clinical implications of HER-2/neu (HER2) expression in ductal carcinoma in
      situ (DCIS) lesions have yet to be clearly elucidated; this despite the more
      frequent expression of HER2 in high-grade DCIS lesions compared with invasive
      cancers. We hypothesized that HER2 overexpression in DCIS is associated with more
      rapid progression to invasive disease. Immunohistochemical staining for estrogen
      receptor, progesterone receptor, and HER2 was done on DCIS specimens. Univariate
      analysis and a multivariate logistic regression were done to determine whether
      estrogen receptor, progesterone receptor, or HER2 status, comedo necrosis,
      nuclear grade, lesion size, or patient age predicted the presence of associated
      invasive disease in patients with DCIS. Invasive foci were found in association
      with HER2 overexpressing DCIS at a higher frequency than with DCIS that did not
      overexpress HER2. Although high nuclear grade, large lesion size, and HER2
      overexpression were all associated with the presence of invasive disease on
      univariate analysis, HER2 was the only significant predictor for the presence of
      invasive disease after multivariate adjustment (odds ratio, 6.4; P = 0.01). These
      data indicate that HER2 overexpression in DCIS lesions predicts the presence of
      invasive foci in patients with DCIS and suggest that targeting of HER2 in an
      early disease setting may forestall or prevent disease progression.

PMID- 19383889
TI  - Physical activity and health outcomes three months after completing a physical
      activity behavior change intervention: persistent and delayed effects.
AB  - PURPOSE: We previously reported the effectiveness of a 12-week physical activity
      behavior change intervention for breast cancer survivors postintervention with
      this report, aiming to determine delayed and/or persistent effects 3 months after
      intervention completion. METHODS: Forty-one sedentary women with stage I, II, or
      IIIA breast cancer currently receiving hormonal therapy were randomly assigned to
      receive the 12-week Better Exercise Adherence after Treatment for Cancer
      intervention or usual care. Assessments occurred at baseline, postintervention,
      and 3 months postintervention. RESULTS: Weekly minutes of greater than or equal
      to moderate intensity physical activity measured by accelerometer showed a
      significant group by time interaction (F = 3.51; P = 0.035; between group
      difference in the mean change from baseline to 3 months postintervention, 100.1
      minute, P = 0.012). Significant group by time interactions also showed sustained
      improvements from baseline to 3 months postintervention in strength (F = 3.82; P
      = 0.027; between group difference, 11.2 kg; P = 0.026), waist-to-hip ratio (F =
      3.36; P = 0.041; between group difference, -0.04; P = 0.094), and social well
      being (F = 4.22; P = 0.023; between group difference, 3.9; P = 0.039). A delayed
      reduction in lower extremity dysfunction 3 months postintervention was noted (F =
      3.24; P = 0.045; between group difference in the mean change from
      postintervention to 3 months follow-up; P = -7.6; P = 0.015). No group by time
      effect was noted for fitness, body mass index, percent fat, bone density, total
      quality of life (Functional Assessment of Cancer Therapy-General), fatigue,
      endocrine symptoms, cognitive function, or sleep. CONCLUSIONS: The intervention
      resulted in sustained improvements in physical activity, strength, central
      adiposity, and social well-being with lower extremity function benefits appearing
      3 months after intervention completion. Testing translation in a multisite study
      is warranted.

PMID- 19383890
TI  - A decreased ratio of laminin-332 beta3 to gamma2 subunit mRNA is associated with
      poor prognosis in colon cancer.
AB  - Laminin-332 (Ln-332) is a heterotrimeric glycoprotein (alpha3beta3gamma2) unique
      to epithelial cells with crucial roles in signaling, adhesion, and migration.
      Altered localization or expression levels of Ln-332, particularly its gamma2
      subunit, are of prognostic value in a variety of cancers. However, the lack of
      standardized methodology and the limited quantification of previous study results
      have left unanswered questions, including the role of gamma2 transcript variants
      and whether differential expression of this chain represents dysregulation of the
      whole heterotrimer. Herein, we test the hypothesis that mRNA changes in one or
      more Ln-332 encoding genes can be used to distinguish between early- and advanced
      stage cancer specimens and shed light on mechanistic questions raised by previous
      studies. Statistical analyses of human microarray data from the publicly
      available expression project in Oncology (expO) dataset, including examination of
      the distributions of Ln-332 subunit mRNA levels, identified a significant
      decrease in the Ln-332 beta3:gamma2 mRNA ratio between normal (n = 10) and early
      stage colon cancer (n = 29) specimens. The beta3:gamma2 ratio was further
      decreased in metastatic colon cancer (n = 41) compared with early-stage samples.
      Our findings raise the possibility that Ln-332 gamma2 may be a therapeutic target
      against metastatic colon cancer because a lowered beta3:gamma2 ratio would reduce
      expression of heterotrimeric Ln-332 and increase monomeric gamma2 secretion.
      Further, standardized, quantitative methods for patient prognosis and therapeutic
      choice could be developed based upon the Ln-332 mRNA changes we uncovered.

PMID- 19383891
TI  - Higher prevalence of secretory CSE1L/CAS in sera of patients with metastatic
      cancer.
AB  - Metastatic markers are highly useful diagnostic and prognostic indicators of
      cancer metastasis. Herein, we report that secretory CSE1L/CAS, a cellular
      apoptosis susceptibility protein, is a new marker for metastatic cancer. CAS was
      colocalized with matrix metalloproteinase-2 in vesicles surrounding the outside
      of MCF-7 cell membranes, and the COOH-terminal domain of CAS was associated with
      matrix metalloproteinase-2-containing vesicles. Immunohistochemical staining for
      CAS was positive in the stroma and gland lumens of human metastatic cancer
      tissues. CAS was also detected in conditioned medium from B16-F10 melanoma cells
      and more frequently in the sera of patients with metastatic cancer than in sera
      from patients with primary cancer. Specifically, the prevalence of serum CAS in
      serum samples from 146 patients was 58.2% (32 of 55), 32.0% (8 of 25), and 12.1%
      (8 of 66) for patients with metastatic, invasive, and primary cancers,
      respectively. Our results suggest that CAS is a secretory protein associated with
      cancer metastasis, which may have clinical utility in metastatic cancer screening
      and diagnosis.

PMID- 19383892
TI  - Screening for gastric cancer in Korea: population-based preferences for endoscopy
      versus upper gastrointestinal series.
AB  - This study assessed the screening rates for gastric cancer by two different
      screening methods, upper gastrointestinal (UGI) series and endoscopy; intentions
      to undergo future gastric cancer screening; and the preferred method of
      screening. The study population was derived from the 2006 Korean National Cancer
      Screening Survey. The Korean National Cancer Screening Survey is an annual cross
      sectional survey that uses nationally representative random sampling to
      investigate cancer screening rates. A total of 1,625 Koreans over 40 years of age
      participated in this study. Logistic regression was used to identify the factors
      associated with undergoing gastric cancer screening, having an intention to be
      screened, and preferring one of the two screening tests. Among the 1,625
      subjects, 15.1% had received a UGI, 33.2% had received an endoscopy, and 43.1%
      had undergone either or both of the tests in the previous 2 years. About 52% of
      people reported the intention to be screened within the next 2 years. The odds
      ratio for intending to be screened was 11.8 and 6.2 higher among those who had
      undergone a prior UGI test and an endoscopy test within the previous 2 years,
      respectively, than for those who had never been screened. Among the 1,625
      individuals, 67% chose endoscopy and 33% UGI for their preferred future screening
      method. Collectively, our results highlight the preference for endoscopy testing
      as a gastric cancer screening method. Providers' assessments of individuals'
      screening preferences in combination with intervention strategies to promote
      performance of the preferred test may increase patient compliance with gastric
      cancer screening recommendations.

PMID- 19383893
TI  - Risk of endometrial cancer in relation to medical conditions and medication use.
AB  - We studied the relation of medical conditions related to obesity and medications
      used for these conditions with endometrial cancer. We also investigated the
      association of other medical conditions and medications with risk. This U.S.
      population-based case-control study included 469 endometrial cancer cases and 467
      controls. Information on putative risk factors for endometrial cancer was
      collected through personal interviews. We asked women about their medical history
      and medications used for six months or longer and the number of years each
      medication was taken. Risk was strongly associated with increasing obesity (P for
      trend < 0.001). Among the conditions related to obesity, and after adjustment for
      age, body mass index, and other risk factors and conditions, uterine fibroids
      were independently related to an increased cancer risk [adjusted odds ratio (OR),
      1.8; 95% confidence interval (95% CI), 1.2-2.5]. Although hypertension was not
      significantly related to endometrial cancer after adjustment for age and body
      mass index, the use of thiazide diuretics was independently associated with
      increased risk (OR, 1.8; 95% CI, 1.1-3.0). Anemia was associated with decreased
      risk (OR, 0.6; 95% CI, 0.5-0.9). Use of nonsteroidal anti-inflammatory drugs was
      related to a decreased risk (OR, 0.7; 95% CI, 0.5-0.97). To our knowledge, the
      observation about thiazide diuretics is novel and requires confirmation in other
      studies and populations.

PMID- 19383894
TI  - Genetic polymorphisms in the catechol estrogen metabolism pathway and breast
      cancer risk.
AB  - BACKGROUND: This study investigated whether single nucleotide polymorphisms (SNP)
      in genes within the catechol estrogen metabolism pathway altered the risk of
      breast cancer alone or in combination, as well as whether menopausal hormone
      therapy modified the effect of these SNPs on breast cancer risk. METHODS: In a
      population-based case-control study of breast cancer, 891 cases and 878 controls
      were genotyped for six functional SNPs in the COMT, CYP1B1, GSTM1, GSTP1, and
      GSTT1 genes. RESULTS: Women homozygous with the T allele in CYP1B1*2 (Ser(119);
      rs1056827) were at 1.69 (95% confidence interval, 1.17-2.46) times the risk of
      women homozygous with the G allele; women homozygous with the G allele in GSTP1
      (Val(105); rs1695) were at 0.73 (95% confidence interval, 0.54-0.99) times the
      risk of breast cancer compared with women homozygous with the A allele. No other
      SNPs tested were associated with breast cancer to any appreciable degree.
      Potential gene-gene and gene-hormone therapy interactions were investigated.
      CONCLUSION: With the exception of GSTP1 and possibly CYP1B1*2, our findings do
      not provide support for the role of genetic variation in the catechol estrogen
      metabolism pathway and breast cancer risk in postmenopausal women.

PMID- 19383895
TI  - Association of diabetes and body mass index with levels of prostate-specific
      antigen: implications for correction of prostate-specific antigen cutoff values?
AB  - BACKGROUND: In a recent study, an inverse association between diabetes and
      prostate-specific antigen (PSA) levels was observed, and several studies reported
      lower PSA levels in groups with higher body mass index. However, all of the
      studies were conducted in populations with intensive PSA screening and the role
      of diabetes severity, duration, and therapy are yet to be explored. METHODS:
      Associations of diabetes duration and treatment, hemoglobin A1c, and BMI with PSA
      levels were assessed among 778 men ages 50 to 74 years, randomly chosen from the
      2000 to 2002 baseline recruitment of a large population-based cohort study in
      Germany (prevalence of diabetes, 17%), using linear regression analyses. RESULTS:
      PSA values were significantly reduced in men with insulin treatment (-39%; P =
      0.006) and oral diabetic medication (-24%; P = 0.030), and in men with elevated
      (6.1-6.9%) and highly (> or =7%) elevated hemoglobin A1c values (-15%, P = 0.004
      and -29%, P = 0.003, respectively). PSA reduction was not associated with
      duration of diabetes. Obesity was possibly associated with a reduction of PSA
      levels (-14%; P = 0.096). CONCLUSIONS: Our study suggests that more severe forms
      of diabetes are associated with lower PSA levels and confirms the magnitude of
      reduction in PSA levels in diabetic men overall. The observed PSA reduction
      parallels reported risk reduction of prostate cancer among diabetic men.

PMID- 19383896
TI  - The WD40 repeat protein NEDD1 functions in microtubule organization during cell
      division in Arabidopsis thaliana.
AB  - Although cells of flowering plants lack a structurally defined microtubule
      organizing center like the centrosome, organization of the spindles and
      phragmoplasts in mitosis is known to involve the evolutionarily conserved gamma
      tubulin complex. We have investigated the function of Arabidopsis thaliana NEDD1,
      a WD40 repeat protein related to the animal NEDD1/GCP-WD protein, which interacts
      with the gamma-tubulin complex. The NEDD1 protein decorates spindle microtubules
      (MTs) preferentially toward spindle poles and phragmoplast MTs toward their minus
      ends. A T-DNA insertional allele of the single NEDD1 gene was isolated and
      maintained in heterozygous sporophytes, and NEDD1's function in cell division was
      analyzed in haploid microspores produced by the heterozygote. In approximately
      half of the dividing microspores exhibiting aberrant MT organization, spindles
      were no longer restricted to the cell periphery and became abnormally elongated.
      After mitosis, MTs aggregated between reforming nuclei but failed to appear in a
      bipolar configuration. Consequently, defective microspores did not form a
      continuous cell plate, and two identical nuclei were produced with no
      differentiation into generative and vegetative cells. Our results support the
      notion that the plant NEDD1 homolog plays a critical role in MT organization
      during mitosis, and its function is likely linked to that of the gamma-tubulin
      complex.

PMID- 19383897
TI  - Identifying new components participating in the secondary cell wall formation of
      vessel elements in zinnia and Arabidopsis.
AB  - Xylem vessel elements are hollow cellular units that assemble end-to-end to form
      a continuous vessel throughout the plant body; the xylem vessel is strengthened
      by the xylem elements' reinforced secondary cell walls (SCWs). This work aims to
      unravel the contribution of unknown actors in xylem vessel differentiation using
      the model in vitro cell culture system of Zinnia elegans differentiating cell
      cultures and the model in vivo system of Arabidopsis thaliana plants. Tracheary
      Element Differentiation-Related6 (TED6) and TED7 were selected based on an RNA
      interference (RNAi) screen in the Zinnia system. RNAi reduction of TED6 and 7
      delayed tracheary element (TE) differentiation and co-overexpression of TED6 and
      7 increased TE differentiation in cultured Zinnia cells. Arabidopsis TED6 and 7
      were expressed preferentially in differentiating vessel elements in seedlings.
      Aberrant SCW formation of root vessel elements was induced by transient RNAi of
      At TED7 alone and enhanced by inhibition of both TED6 and 7. Protein-protein
      interactions were demonstrated between TED6 and a subunit of the SCW-related
      cellulose synthase complex. Our strategy has succeeded in finding two novel
      components in SCW formation and has opened the door for in-depth analysis of
      their molecular functions.

PMID- 19383898
TI  - When the sphingosine kinase 1/sphingosine 1-phosphate pathway meets hypoxia
      signaling: new targets for cancer therapy.
AB  - The reduction in the normal level of tissue oxygen tension or hypoxia is a
      characteristic of solid tumors that triggers the activation of signaling pathways
      promoting neovascularization, metastasis, increased tumor growth, and resistance
      to treatments. The activation of the transcription factor hypoxia-inducible
      factor 1alpha (HIF-1alpha) has been identified as the master mechanism of
      adaptation to hypoxia. In a recent study, we identified the sphingosine kinase
      1/sphingosine 1-phosphate (SphK1/S1P) pathway, which elicits various cellular
      processes including cell proliferation, cell survival, or angiogenesis, as a new
      modulator of HIF-1alpha activity under hypoxic conditions. Here, we consider how
      the SphK1/S1P signaling pathway could represent a very important target for
      therapeutic intervention in cancer.

PMID- 19383899
TI  - TGF-beta1 + EGF-initiated invasive potential in transformed human keratinocytes
      is coupled to a plasmin/MMP-10/MMP-1-dependent collagen remodeling axis: role for
      PAI-1.
AB  - The phenotypic switching called epithelial-to-mesenchymal transition is
      frequently associated with epithelial tumor cell progression from a comparatively
      benign to an aggressive, invasive malignancy. Coincident with the emergence of
      such cellular plasticity is an altered response to transforming growth factor
      beta (TGF-beta) as well as epidermal growth factor (EGF) receptor amplification.
      TGF-beta in the tumor microenvironment promotes invasive traits largely through
      reprogramming gene expression, which paradoxically supports matrix-disruptive as
      well as stabilizing processes. ras-transformed HaCaT II-4 keratinocytes undergo
      phenotypic changes typical of epithelial-to-mesenchymal transition, acquire a
      collagenolytic phenotype, and effectively invade collagen type 1 gels as a
      consequence of TGF-beta1 + EGF stimulation in a three-dimensional physiologically
      relevant model system that monitors collagen remodeling. Enhanced collagen
      degradation was coupled to a significant increase in matrix metalloproteinase
      (MMP)-10 expression and involved a proteolytic axis composed of plasmin, MMP-10,
      and MMP-1. Neutralization of any one component in this cascade inhibited collagen
      gel lysis. Similarly, addition of plasminogen activator inhibitor type 1
      (SERPINE1) blocked collagen degradation as well as the conversion of both proMMP
      10 and proMMP-1 to their catalytically active forms. This study therefore
      identifies an important mechanism in TGF-beta1 + EGF-initiated collagen
      remodeling by transformed human keratinocytes and proposes a crucial upstream
      role for plasminogen activator inhibitor type 1-dependent regulation in this
      event.

PMID- 19383900
TI  - Wnt/beta-catenin signaling regulates cytokine-induced human inducible nitric
      oxide synthase expression by inhibiting nuclear factor-kappaB activation in
      cancer cells.
AB  - The human inducible nitric oxide synthase (hiNOS) gene is regulated by nuclear
      factor kappaB (NF-kappaB) and has recently been shown to be a target of the
      Wnt/beta-catenin pathway. In this study, we tested the hypothesis that Wnt/beta
      catenin signaling might regulate cytokine- or tumor necrosis factor alpha
      (TNFalpha)-induced hiNOS expression through interaction with NF-kappaB. A
      cytokine mixture of TNFalpha + interleukin (IL)-1beta + IFNgamma induced a 2- to
      3-fold increase in hiNOS promoter activity in HCT116 and DLD1 colon cells, but
      produced a 2-fold decrease in SW480 colon cancer cells. A similar differential
      activity was seen in liver cancer cells (HepG2, Huh7, and Hep3B). Overexpression
      of beta-catenin produced a dose-dependent decrease in NF-kappaB reporter activity
      and decreased cytokine mixture-induced hiNOS promoter activity. Gel shift for
      TNFalpha-induced hiNOS NF-kappaB activation showed decreased p50 binding and
      decreased NF-kappaB reporter activity in the beta-catenin-mutant HAbeta18 cells.
      Conversely, enhanced p50 binding and increased NF-kappaB reporter activity were
      seen in HAbeta85 cells, which lack beta-catenin signaling. Coimmunoprecipitation
      confirmed that beta-catenin complexed with both p65 and p50 NF-kappaB proteins.
      NF-kappaB-dependent Traf1 protein expression also inversely correlated with the
      level of beta-catenin. Furthermore, SW480 cells stably transformed with wild-type
      adenomatous polyposis coli showed decreased beta-catenin protein and increased
      TNFalpha-induced p65 NF-kappaB binding as well as iNOS and Traf1 expression.
      Finally, beta-catenin inversely correlated with iNOS and Fas expression in vivo
      in hepatocellular carcinoma tumor samples. Our in vitro and in vivo data show
      that beta-catenin signaling inversely correlates with cytokine-induced hiNOS and
      other NF-kappaB-dependent gene expression. These findings underscore the complex
      role of Wnt/beta-catenin, NF-kappaB, and iNOS signaling in the pathophysiology of
      inflammation-associated carcinogenesis.

PMID- 19383901
TI  - Genetic variation in B-cell-activating factor is associated with an increased
      risk of developing B-cell non-Hodgkin lymphoma.
AB  - Elevated B-cell-activating factor (BAFF; TNFSF13B) levels have been found in
      patients with B-cell malignancies and autoimmune diseases, suggesting that it may
      play a pathogenic role. We previously found that a single nucleotide polymorphism
      (SNP) in the TNFSF13B promoter resulted in increased transcription, suggesting
      that genetic variation in TNFSF13B may influence its expression. We therefore
      wanted to determine if genetic variation in TNFSF13B is associated with high BAFF
      levels and non-Hogkin lymphoma (NHL) risk. We genotyped 9 tagSNPs within TNFSF13B
      in a clinic-based study of 441 NHL cases and 475 matched controls and evaluated
      the association of individual SNPs with risk of NHL; 3 tagSNPs were significant
      (P < 0.05). When categorized into low-, moderate-, and high-risk groups based on
      risk alleles, we found the permutation-corrected odds ratio for the trend to be
      1.43 (P = 0.0019) for risk of B-cell NHL, 1.69 (P = 0.0093) for diffuse large B
      cell lymphoma, 1.43 (P = 0.029) for follicular lymphoma, and 1.06 (P = 0.21) for
      chronic lymphocytic leukemia/small lymphocytic lymphoma. The mean serum BAFF
      level in those who carried the low-risk alleles was 2 ng/mL compared with 4.3
      ng/mL in those with the high-risk alleles (P = 0.02). Taken together, our data
      suggest that genetic variation in the TNFSF13B gene is significantly associated
      with NHL risk and elevated serum BAFF levels.

PMID- 19383902
TI  - Associations between alpha-tocopherol, beta-carotene, and retinol and prostate
      cancer survival.
AB  - Previous studies suggest that carotenoids and tocopherols (vitamin E compounds)
      may be inversely associated with prostate cancer risk, yet little is known about
      how they affect prostate cancer progression and survival. We investigated whether
      serum alpha-tocopherol, beta-carotene, and retinol concentrations, or the alpha
      tocopherol and beta-carotene trial supplementation, affected survival of men
      diagnosed with prostate cancer during the alpha-Tocopherol, beta-Carotene Cancer
      Prevention Study, a randomized, double-blind, placebo-controlled primary
      prevention trial testing the effects of beta-carotene and alpha-tocopherol
      supplements on cancer incidence in adult male smokers in southwestern Finland (n
      = 29,133). Prostate cancer survival was examined using the Kaplan-Meier method
      with deaths from other causes treated as censoring, and using Cox proportional
      hazards regression models with hazard ratios (HR) and 95% confidence intervals
      (CI) adjusted for family history of prostate cancer, age at randomization, benign
      prostatic hyperplasia, age and stage at diagnosis, height, body mass index, and
      serum cholesterol. As of April 2005, 1,891 men were diagnosed with prostate
      cancer and 395 died of their disease. Higher serum alpha-tocopherol at baseline
      was associated with improved prostate cancer survival (HR, 0.67; 95% CI, 0.45
      1.00), especially among cases who had received the alpha-tocopherol intervention
      of the trial and who were in the highest quintile of alpha-tocopherol at baseline
      (HR, 0.51; 95% CI, 0.20-0.90) or at the 3-year follow-up measurement (HR, 0.26;
      95% CI, 0.09-0.71). Serum beta-carotene, serum retinol, and supplemental beta
      carotene had no apparent effects on survival. These findings suggest that higher
      alpha-tocopherol (and not beta-carotene or retinol) status increases overall
      prostate cancer survival. Further investigations, possibly including randomized
      studies, are needed to confirm this observation.

PMID- 19383903
TI  - Transcription inhibition of heat shock proteins: a strategy for combination of 17
      allylamino-17-demethoxygeldanamycin and actinomycin d.
AB  - The heat shock protein (HSP) 90 inhibitor 17-allylamino-17-demethoxygeldanamycin
      (17-AAG) is currently in clinical trials because of its unique mechanism of
      action and antitumor activity. However, 17-AAG triggers the transcription and
      elevation of antiapoptotic HSP90, HSP70, and HSP27, which lead to chemoresistance
      in tumor cells. We hypothesized that inhibiting HSP90, HSP70, and HSP27
      transcription may enhance 17-AAG-induced cell death in multiple myeloma cell
      lines. Actinomycin D (Act D), a clinically used agent and transcription
      inhibitor, was combined with 17-AAG. The concentrations for 17-AAG and Act D were
      selected based on the target actions and plasma levels during therapy. Inducible
      and constitutive HSP27, HSP70, and HSP90 mRNA and protein levels were measured by
      real-time reverse transcription-PCR and immunoblot assays. Compared with no
      treatment, Act D alone decreased HSP mRNA levels in MM.1S and RPMI-8226 cell
      lines. Combining Act D with 17-AAG did not attenuate 17-AAG-mediated increases in
      transcript levels of inducible HSP70; however, constitutive HSP mRNA levels were
      decreased. In contrast to its effect on mRNA levels, Act D was able to abrogate
      17-AAG-mediated increases in all HSP protein levels. The cytotoxicity of combined
      Act D and 17-AAG was assessed. Treatment with Act D alone caused <40% cell death,
      whereas the combination of 17-AAG and Act D resulted in an increase of cell death
      in both multiple myeloma cell lines. In conclusion, these results indicate that
      17-AAG-mediated induction of HSP70 and HSP27 expression can be attenuated by Act
      D and therefore can potentially improve the clinical treatment of multiple
      myeloma.

PMID- 19383904
TI  - Development of a multiplex quantitative PCR signature to predict progression in
      non-muscle-invasive bladder cancer.
AB  - In bladder cancer, clinical grade and stage fail to capture outcome. We developed
      a clinically applicable quantitative PCR (QPCR) gene signature to predict
      progression in non-muscle-invasive bladder cancer. Comparative metaprofiling of
      12 DNA microarray data sets (comprising 631 samples and 241,298 probe sets)
      identified 96 genes, which showed differential expression in seven clinical
      outcome categories, or were identified as outliers, historic markers, or
      housekeeping genes. QPCR was done to determine mRNA expression from 96 bladder
      tumors. Fifty-seven genes differentiated T2 from non-T2 tumors (P < 0.05).
      Principal components analysis and Cox regression models were used to predict
      probability of T2 progression for non-T2 patients, placing them into high- and
      low-risk groups based on their gene expression. At 2 years, high-risk patients
      exhibited greater T2 progression (45% for high-risk patients versus 12% for low
      risk patients; P = 0.003, log-rank test). This difference remained significant
      within T1 tumors (61% for high-risk patients versus 22% for low-risk patients; P
      = 0.02) and Ta tumors (29% for high-risk patients versus 0% for low-risk
      patients; P = 0.03). The best multivariate Cox model included stage and gender,
      and this signature provided predictive improvement over both (P = 0.002,
      likelihood ratio test). Immunohistochemistry was done for two genes in the
      signature not previously described in bladder cancer, ACTN1 and CDC25B,
      corroborating their up-regulation at the protein level with disease progression.
      Thus, we identified a 57-gene QPCR panel to help predict progression of non
      muscle-invasive bladder cancers and delineate a systematic, generalizable
      approach to converting microarray data into a multiplex assay for cancer
      progression.

PMID- 19383905
TI  - The steroid receptor coactivator-1 regulates twist expression and promotes breast
      cancer metastasis.
AB  - In breast cancer, steroid receptor coactivator-1 (SRC-1) expression positively
      correlates with HER2 expression and poor prognosis. In mouse mammary tumor virus
      polyoma middle T (PyMT) breast cancer mouse model, SRC-1 strongly promotes
      mammary tumor metastasis. However, the molecular targets and mechanisms that
      mediate the role of SRC-1 in metastasis are unknown. In this study, SRC-1 wild
      type (WT) and knockout (KO) cell lines were developed from the mammary tumors of
      WT/PyMT and KO/PyMT mice. WT cells exhibited strong migration and invasion
      capabilities, reduced E-cadherin and beta-catenin epithelial markers, gained N
      cadherin and vimentin mesenchymal markers, and formed undifferentiated invasive
      structures in three-dimensional culture. In contrast, KO cells showed slow
      migration and invasion, retained E-cadherin, had less N-cadherin and vimentin,
      and developed partially differentiated three-dimensional structures. Importantly,
      WT cells expressed Twist, a master regulator of metastasis, at significantly
      higher levels versus KO cells. SRC-1 knockdown in WT cells reduced Twist
      expression, whereas SRC-1 restoration in KO cells also rescued Twist expression.
      Furthermore, SRC-1 was found to coactivate Twist transcription through physical
      interaction with the transcription factor PEA3 at the proximal Twist promoter.
      Accordingly, Twist knockdown in WT cells increased E-cadherin and reduced cell
      invasion and metastasis, and Twist expression in KO cells decreased E-cadherin
      and increased cell invasion. SRC-1 knockdown in human breast cancer cells also
      decreased Twist, cell migration, and invasion. Therefore, SRC-1 promotes breast
      cancer invasiveness and metastasis by coactivating PEA3-mediated Twist
      expression. Intervention of SRC-1 function may provide new strategies to inhibit
      breast cancer metastasis.

PMID- 19383906
TI  - Catecholamines regulate tumor angiogenesis.
AB  - Among the regulators of angiogenesis, catecholamine neurotransmitters are of
      recent interest because of their opposite roles in the regulation of tumor
      neovascularization. Norepinephrine and epinephrine by acting through specific
      adrenoceptors increase the synthesis of proangiogenic factors, and thereby,
      promote tumor growth. In contrast, dopamine acting via its specific D(2)
      receptors inhibits tumor growth by suppressing the actions of vascular
      permeability factor/vascular endothelial growth factor-A on both tumor
      endothelial and bone marrow-derived endothelial progenitor cells. These reports
      identify novel endogenous regulators of tumor angiogenesis and also indicate a
      new and an inexpensive class of antiangiogenic drugs for the treatment of cancer.

PMID- 19383907
TI  - CD38/CD31, the CCL3 and CCL4 chemokines, and CD49d/vascular cell adhesion
      molecule-1 are interchained by sequential events sustaining chronic lymphocytic
      leukemia cell survival.
AB  - CD38 and CD49d are associated negative prognosticators in chronic lymphocytic
      leukemia (CLL). Despite evidence that both molecules are involved in interactions
      occurring between CLL and normal cells in the context of CLL-involved tissues, a
      functional link is still missing. Using gene expression profiles comparing
      CD38(+)CD49d(+) versus CD38(-)CD49d(-) CLL cells, we showed overexpression of the
      CCL3 and CCL4 chemokines in cells from the former group. These chemokines were
      also up-regulated by CD38 signals in CLL; moreover, CCL3 was expressed by CLL
      cells from bone marrow biopsies (BMB) of CD38(+)CD49d(+) but not CD38(-)CD49d(-)
      cases. High levels of CCR1 and, to a lesser extent, CCR5, the receptors for CCL3
      and CCL4, were found in CLL-derived monocyte-macrophages. Consistently, CCL3
      increased monocyte migration, and CD68(+) macrophage infiltration was
      particularly high in BMB from CD38(+)CD49d(+) CLL. Conditioned media from CCL3
      stimulated macrophages induced endothelial cells to express vascular cell
      adhesion molecule-1 (VCAM-1), the CD49d ligand, likely through tumor necrosis
      factor alpha overproduction. These effects were apparent in BMB from
      CD38(+)CD49d(+) CLL, where lymphoid infiltrates were characterized by a prominent
      meshwork of VCAM-1(+) stromal/endothelial cells. Lastly, CD49d engagement by VCAM
      1 transfectants increased viability of CD38(+)CD49d(+) CLL cells. Altogether,
      CD38 and CD49d can be thought of as parts of a consecutive chain of events
      ultimately leading to improved survival of CLL cells.

PMID- 19383908
TI  - B-MYB is required for recovery from the DNA damage-induced G2 checkpoint in p53
      mutant cells.
AB  - In response to DNA damage, several signaling pathways that arrest the cell cycle
      in G(1) and G(2) are activated. The down-regulation of mitotic genes contributes
      to the stable maintenance of the G(2) arrest. The human LINC or DREAM complex,
      together with the B-MYB transcription factor, plays an essential role in the
      expression of G(2)-M genes. Here, we show that DNA damage results in the p53
      dependent binding of p130 and E2F4 to LINC and the dissociation of B-MYB from
      LINC. We find that B-MYB fails to dissociate from LINC in p53 mutant cells, that
      this contributes to increased G(2)-M gene expression in response to DNA damage in
      these cells, and, importantly, that B-MYB is required for recovery from the G(2)
      DNA damage checkpoint in p53-negative cells. Reanalysis of microarray expression
      data sets revealed that high levels of B-MYB correlate with a p53 mutant status
      and an advanced tumor stage in primary human breast cancer. Taken together, these
      data suggest that B-MYB/LINC plays an important role in the DNA damage response
      downstream of p53.

PMID- 19383909
TI  - Identification of Smyd4 as a potential tumor suppressor gene involved in breast
      cancer development.
AB  - To identify genes involved in breast tumorigenesis, we applied the retroviral
      LoxP-Cre system to a nontumorigenic mouse mammary epithelial cell line NOG8 to
      create random chromosome deletion/translocation. We found that the disruption of
      one allele of Smyd4 (SET and MYND domain containing 4) gene through chromosome
      translocation led to tumorigenesis. The expression of Smyd4 was markedly
      decreased in tumor cells. Re-expression of Smyd4 resulted in growth suppression
      of tumor cells and inhibition of tumor formation in nude mice. Furthermore, the
      RNA interference-mediated suppression of Smyd4 expression in human MCF10A mammary
      epithelial cells caused their growth in soft agar. Microarray studies revealed
      that platelet-derived growth factor receptor alpha polypeptide (Pdgfr-alpha) was
      highly expressed in tumor cells compared with NOG8 cells. Re-expression of Smyd4
      significantly reduced the expression of Pdgfr-alpha in tumor cells. In human
      breast cancers, reverse transcription-PCR results revealed that Smyd4 expression
      was totally silenced in 2 of 10 specimens. These findings indicate that Smyd4, as
      a potential tumor suppressor, plays a critical role in breast carcinogenesis at
      least partly through inhibiting the expression of Pdgfr-alpha, and could be a
      novel target for improving treatment of breast cancer.

PMID- 19383910
TI  - Caspase-8 association with the focal adhesion complex promotes tumor cell
      migration and metastasis.
AB  - Caspase-8 is a proapoptotic protease that suppresses neuroblastoma metastasis by
      inducing programmed cell death. Paradoxically, caspase-8 can also promote cell
      migration among nonapoptotic cells; here, we show that caspase-8 can promote
      metastasis when apoptosis is compromised. Migration is enhanced by caspase-8
      recruitment to the cellular migration machinery following integrin ligation.
      Caspase-8 catalytic activity is not required for caspase-8-enhanced cell
      migration; rather, caspase-8 interacts with a multiprotein complex that can
      include focal adhesion kinase and calpain 2 (CPN2), enhancing cleavage of focal
      adhesion substrates and cell migration. Caspase-8 association with
      CPN2/calpastatin disrupts calpastatin-mediated inhibition of CPN2. In vivo,
      knockdown of either caspase-8 or CPN2 disrupts metastasis among apoptosis
      resistant tumors. This unexpected molecular collaboration provides an explanation
      for the continued or elevated expression of caspase-8 observed in many tumors.

PMID- 19383911
TI  - Analysis of DNA copy number alterations in ovarian serous tumors identifies new
      molecular genetic changes in low-grade and high-grade carcinomas.
AB  - Ovarian serous carcinoma, the most common and lethal type of ovarian cancer, is
      thought to develop from two distinct molecular pathways. High-grade (HG) serous
      carcinomas contain frequent TP53 mutations, whereas low-grade (LG) carcinomas
      arise from serous borderline tumors (SBT) and harbor mutations in KRAS/BRAF/ERBB2
      pathway. However, the molecular alterations involved in the progression from SBT
      to LG carcinoma remain unknown. In addition, the extent of deletion of tumor
      suppressors in ovarian serous carcinomas has not been well studied. To further
      address these two issues, we assessed DNA copy number changes among affinity
      purified tumor cells from 37 ovarian serous neoplasms including SBT, LG, and HG
      tumors using high-density 250K single nucleotide polymorphism arrays. Chromosomal
      instability index as measured by changes in DNA copy number was significantly
      higher in HG than in LG serous carcinomas. Hemizygous ch1p36 deletion was common
      in LG serous carcinomas but was rarely seen in SBT. This region contains several
      candidate tumor suppressors including miR-34a. In contrast, in HG serous
      carcinomas, significant numbers of amplifications and deletions, including
      homozygous deletions, were identified. Among homozygous deletions, loci
      containing Rb1, CDKN2A/B, CSMD1, and DOCK4 were most common, being present in
      10.6%, 6.4%, 6.4%, and 4.3%, respectively, in independent 47 affinity-purified HG
      serous carcinomas. Except for the CDKN2A/B region, these homozygous deletions
      were not present in either SBT or LG tumors. Our study provides a genome-wide
      homozygous deletion profile in HG serous carcinomas, which can serve as a
      molecular foundation to study tumor suppressors in ovarian cancer.

PMID- 19383912
TI  - FOXP3 defines regulatory T cells in human tumor and autoimmune disease.
AB  - Activated T cells may express FOXP3. It is thought that FOXP3 is not a specific
      marker to determine regulatory T cells (Treg) in humans. Here, we examined the
      functional phenotype and cytokine profile of the in vitro induced FOXP3(+) T
      cells, primary FOXP3(+) and FOXP3(-) T cells in patients with ulcerative colitis
      and tumors including colon carcinoma, melanoma, hepatic carcinoma, ovarian
      carcinoma, pancreatic cancer, and renal cell carcinoma. We observed similar
      levels of suppressive capacity of primary FOXP3(+) T cells in blood, tumors, and
      colitic tissues. Compared with primary FOXP3(-) T cells in the same
      microenvironment, these primary FOXP3(+) T cells expressed minimal levels of
      effector cytokines, negligible amount of cytotoxic molecule granzyme B, and
      levels of suppressive molecules interleukin-10 and PD-1. Although the in vitro
      activated T cells expressed FOXP3, these induced FOXP3(+) T cells expressed high
      levels of multiple effector cytokines and were not functionally suppressive. The
      data reinforce the fact that FOXP3 remains an accurate marker to define primary
      Tregs in patients with cancer and autoimmune disease. We suggest that the
      combination of FOXP3 and cytokine profile is useful for further functionally
      distinguishing primary Tregs from activated conventional T cells.

PMID- 19383913
TI  - Species-specific in vivo engraftment of the human BL melanoma cell line results
      in an invasive dedifferentiated phenotype not present in xenografts.
AB  - For clinically relevant studies on melanoma progression and invasiveness, in vivo
      experimental systems with a human cellular microenvironment would be
      advantageous. We have compared tumor formation from a human cutaneous malignant
      melanoma cell line (BL), after injection as conventional xenografts in the mouse,
      or when injected into a predominantly species-specific environment of human
      embryonic stem cell-derived teratoma induced in the mouse (the hEST model). The
      resulting melanoma histology was generally analogous, both systems showing
      delimited densely packed areas with pleomorphic cells of malignant appearance. A
      specificity of the integration process into the human embryonic teratoma tissues
      was indicated by the melanoma exclusively being found in areas compatible with
      condensed mesenchyme, similar to neural crest development. Here, also enhanced
      neovascularization was seen within the human mesenchymal tissues facing the BL
      melanoma growth. Furthermore, in the hEST model an additional melanoma cell
      phenotype occurred, located at the border of, or infiltrating into, the
      surrounding human loose mesenchymal fibrous stroma. This BL population had a
      desmoplastic spindle-like appearance, with markers indicative of
      dedifferentiation and migration. The appearance of this apparently more
      aggressive phenotype, as well as the induction of human angiogenesis, shows
      specific interactions with the human embryonic microenvironment in the hEST
      model. In conclusion, these data provide exciting options for using the hEST
      model in molecular in vivo studies on differentiation, invasiveness, and
      malignancy of human melanoma, while analyzing species-specific reactions in vivo.

PMID- 19383914
TI  - Expansion of highly cytotoxic human natural killer cells for cancer cell therapy.
AB  - Infusions of natural killer (NK) cells are an emerging tool for cancer
      immunotherapy. The development of clinically applicable methods to produce large
      numbers of fully functional NK cells is a critical step to maximize the potential
      of this approach. We determined the capacity of the leukemia cell line K562
      modified to express a membrane-bound form of interleukin (IL)-15 and 41BB ligand
      (K562-mb15-41BBL) to generate human NK cells with enhanced cytotoxicity. Seven
      day coculture with irradiated K562-mb15-41BBL induced a median 21.6-fold
      expansion of CD56(+)CD3(-) NK cells from peripheral blood (range, 5.1- to 86.6
      fold; n = 50), which was considerably superior to that produced by stimulation
      with IL-2, IL-12, IL-15, and/or IL-21 and caused no proliferation of CD3(+)
      lymphocytes. Similar expansions could also be obtained from the peripheral blood
      of patients with acute leukemia undergoing therapy (n = 11). Comparisons of the
      gene expression profiles of the expanded NK cells and their unstimulated or IL-2
      stimulated counterparts showed marked differences. The expanded NK cells were
      significantly more potent than unstimulated or IL-2-stimulated NK cells against
      acute myeloid leukemia cells in vitro. They could be detected for >1 month when
      injected into immunodeficient mice and could eradicate leukemia in murine models
      of acute myeloid leukemia. We therefore adapted the K562-mb15-41BBL stimulation
      method to large-scale clinical-grade conditions, generating large numbers of
      highly cytotoxic NK cells. The results that we report here provide rationale and
      practical platform for clinical testing of expanded and activated NK cells for
      cell therapy of cancer.

PMID- 19383915
TI  - eIF4E activation is commonly elevated in advanced human prostate cancers and
      significantly related to reduced patient survival.
AB  - Elevated eukaryotic translation initiation factor 4E (eIF4E) function induces
      malignancy in experimental models by selectively enhancing translation of key
      malignancy-related mRNAs (c-myc and BCL-2). eIF4E activation may reflect
      increased eIF4E expression or phosphorylation of its inhibitory binding proteins
      (4E-BP). By immunohistochemical analyses of 148 tissues from 89 prostate cancer
      patients, we now show that both eIF4E expression and 4E-BP1 phosphorylation (p4E
      BP1) are increased significantly, particularly in advanced prostate cancer versus
      benign prostatic hyperplasia tissues. Further, increased eIF4E and p4E-BP1 levels
      are significantly related to reduced patient survival, whereas uniform 4E-BP1
      expression is significantly related to better patient survival. Both
      immunohistochemistry and Western blotting reveal that elevated eIF4E and p4E-BP1
      are evident in the same prostate cancer tissues. In two distinct prostate cancer
      cell models, the progression to androgen independence also involves increased
      eIF4E activation. In these prostate cancer cells, reducing eIF4E expression with
      an eIF4E-specific antisense oligonucleotide currently in phase I clinical trials
      robustly induces apoptosis, regardless of cell cycle phase, and reduces
      expression of the eIF4E-regulated proteins BCL-2 and c-myc. Collectively, these
      data implicate eIF4E activation in prostate cancer and suggest that targeting
      eIF4E may be attractive for prostate cancer therapy.

PMID- 19383916
TI  - Relationship of deregulated signaling converging onto mTOR with prognosis and
      classification of lung adenocarcinoma shown by two independent in silico
      analyses.
AB  - There is marked disparity with a slight overlap among prognosis-predictive
      signatures reported thus far for lung cancers. In this study, we aimed at linking
      poor prognosis with particular pathways and/or functions of the gene sets
      involved to better understand the underlying molecular characteristics associated
      with the prognosis of lung adenocarcinomas. Gene set enrichment analysis
      identified a gene set down-regulated by rapamycin as the most significant,
      whereas several others responsive to withdrawal of glucose or amino acids, which
      are related to signaling converging onto mammalian target of rapamycin (mTOR),
      were also shown to be significantly associated, in addition to those related to
      DNA damage response and cell cycle progression. We also used connectivity map (C
      MAP) analysis, an independent bioinformatics approach, to search for Food and
      Drug Administration-approved drugs that potentially transform an unfavorable
      signature to a favorable one. Those results identified inhibitors of
      phosphatidylinositol 3-kinase (PI3K) and mTOR, as well as unexpected drugs such
      as phenothiazine antipsychotics and resveratrol as potential candidates.
      Experimental validation revealed that the latter unexpected agents also inhibited
      signaling converging onto mTOR and exhibited antitumor activities. In addition,
      deregulation of multiple signaling converging onto mTOR was shown to be
      significantly associated with sensitivity to PI-103, a dual specificity PI3K/mTOR
      inhibitor that is not contained in the C-MAP database, lending further support
      for the connection. Our results clearly show the existence of gene set-definable,
      intrinsic heterogeneities in lung adenocarcinomas, which seem to be related to
      both clinical behavior and sensitivity to agents affecting the identified
      pathways.

PMID- 19383917
TI  - Neoadjuvant vaccination provides superior protection against tumor relapse
      following surgery compared with adjuvant vaccination.
AB  - Tumors that recur following surgical resection of melanoma are typically
      metastatic and associated with poor prognosis. Using the murine B16F10 melanoma
      and a robust antimelanoma vaccine, we evaluated immunization as a tool to improve
      tumor-free survival following surgery. We investigated the utility of vaccination
      in both neoadjuvant and adjuvant settings. Surprisingly, neoadjuvant vaccination
      was far superior and provided approximately 100% protection against tumor
      relapse. Neoadjuvant vaccination was associated with enhanced frequencies of
      tumor-specific T cells within the tumor and the tumor-draining lymph nodes
      following resection. We also observed increased infiltration of antigen-specific
      T cells into the area of surgery. This method should be amenable to any vaccine
      platform and can be readily extended to the clinic.

PMID- 19383918
TI  - Antitumor activity of gammadelta T cells reactive against cytomegalovirus
      infected cells in a mouse xenograft tumor model.
AB  - gammadelta T cells recognize stress-induced autoantigens and contribute to
      immunity against infections and cancer. Our previous study revealed that Vdelta2
      negative ((neg)) gammadelta T lymphocytes isolated from transplant recipients
      infected by cytomegalovirus (CMV) killed both CMV-infected cells and HT29 colon
      cancer cells in vitro. To investigate the antitumor effects of Vdelta2(neg)
      clones in vivo, we generated hypodermal HT29 tumors in immunodeficient mice.
      Concomitant injections of Vdelta2(neg)clones, in contrast to Vdelta2(+) cells,
      prevented the development of HT29 tumors. Vdelta2(neg) clones expressed chemokine
      C-C motif receptor 3 (CCR3) and migrated in vitro in response to chemokines
      secreted by HT29 cells, among which were the CCR3 ligands macrophage inflammatory
      protein-1delta and monocyte chemoattractant protein-4. More importantly, a
      systemic i.p. treatment with Vdelta2(neg) clones delayed the growth of HT29 s.c.
      tumors. The effect of in vivo gammadelta T-cell passive immunotherapy on tumor
      growth could be reverted by addition of a blocking anti-CCR3 antibody. gammadelta
      T-cell passive immunotherapy was dependent on the cytotoxic activity of the
      gammadelta effectors toward their targets because Vdelta2(neg) clones were not
      able to inhibit the growth of A431 hypodermal tumors. Our findings suggest that
      CMV-specific Vdelta2(neg) cells could target in vivo cancer cells, making them an
      attractive candidate for antitumor immunotherapy.

PMID- 19383920
TI  - Prevention of spontaneous tumor development in a ret transgenic mouse model by
      ret peptide vaccination with indoleamine 2,3-dioxygenase inhibitor 1-methyl
      tryptophan.
AB  - The present study investigated an immunotherapeutic strategy for rearranged
      during transfection proto-oncogene (ret)-associated carcinomas in a transgenic
      MT/ret 304/B6 mouse model in which spontaneous tumors develop due to
      overexpression of the ret gene. A Ret peptide vaccine comprising an extracellular
      fragment of Ret protein and Th1-polarized immunoregulator CpG oligonucleotide
      (1826) induced strong and specific cellular and humoral immune responses in wild
      type C57BL/6 mice, showing that the Ret peptide has a strong immunogenic
      potential as part of an antitumor vaccine. In MT/ret 304/B6 mice, however, the
      vaccine was only modestly effective as an inducer of the humoral immune response,
      and it failed to elicit a T-cell response. An immunohistochemical analysis
      revealed marked indoleamine 2,3-dioxygenase expression after immunization with
      Ret peptide vaccine in the lymph nodes and spleens of MT/ret 304/B6 mice. The
      systemic administration of the potent inhibitor of indoleamine 2,3-dioxygenase 1
      methyl tryptophan (1MT) along with Ret vaccine produced a significant increase in
      tumor-specific cytotoxic activity. A delay in spontaneous tumor development was
      also observed in the MT/ret 304/B6 mice to which the Ret vaccine and 1MT were
      administered. These results indicate that an improved Ret vaccine composed of Ret
      peptide plus CpG oligonucleotide plus 1MT is a potential therapeutic strategy for
      treatment of ret-associated carcinomas.

PMID- 19383919
TI  - Doxorubicin and paclitaxel-loaded lipid-based nanoparticles overcome multidrug
      resistance by inhibiting P-glycoprotein and depleting ATP.
AB  - To test the ability of nanoparticle formulations to overcome P-glycoprotein (P
      gp)-mediated multidrug resistance, several different doxorubicin and paclitaxel
      loaded lipid nanoparticles were prepared. Doxorubicin nanoparticles showed 6- to
      8-fold lower IC(50) values in P-gp-overexpressing human cancer cells than those
      of free doxorubicin. The IC(50) value of paclitaxel nanoparticles was over 9-fold
      lower than that of Taxol in P-gp-overexpressing cells. A series of in vitro cell
      assays were used including quantitative studies on uptake and efflux, inhibition
      of calcein acetoxymethylester efflux, alteration of ATP levels, membrane
      integrity, mitochondrial membrane potential, apoptosis, and cytotoxicity.
      Enhanced uptake and prolonged retention of doxorubicin were observed with
      nanoparticle-based formulations in P-gp-overexpressing cells. Calcein
      acetoxymethylester and ATP assays confirmed that blank nanoparticles inhibited P
      gp and transiently depleted ATP. I.v. injection of pegylated paclitaxel
      nanoparticles showed marked anticancer efficacy in nude mice bearing resistant
      NCI/ADR-RES tumors versus all control groups. Nanoparticles may be used to target
      both drug and biological mechanisms to overcome multidrug resistance via P-gp
      inhibition and ATP depletion.

PMID- 19383921
TI  - Poly(ADP-ribose) polymerase-1 inhibitor treatment regresses autochthonous
      Brca2/p53-mutant mammary tumors in vivo and delays tumor relapse in combination
      with carboplatin.
AB  - Germ-line heterozygosity of the BRCA2 gene in women predisposes to breast and
      ovarian cancers. Successful therapies targeted specifically at these neoplasms
      have thus far remained elusive. Recent studies in mice have shown that inhibition
      of poly(ADP-ribose) polymerase-1 (PARP-1) targets cells lacking Brca2 and
      xenografts derived from BRCA2-deficient ES cells or Chinese hamster ovary cells.
      We set out to develop a more relevant preclinical model that will inform and
      accelerate translation into the clinic. As such, we conditionally deleted Brca2
      and p53 within murine mammary epithelium and treated the resulting tumors in situ
      with a highly potent PARP-1 inhibitor (AZD2281) alone or in combination with
      carboplatin. Daily exposure to AZD2281 for 28 days caused significant regression
      or growth inhibition in 46 of 52 tumors. This response was shown to be specific
      to tumors lacking both Brca2and p53. AZD2281/carboplatin combination therapy for
      28 days showed no advantage over carboplatin monotherapy. However, if PARP
      inhibitor treatment was continued, this significantly increased the time to tumor
      relapse and death in these mice. This preclinical study is the first to show in
      vivo hypersensitivity of spontaneously arising Brca2-deficient mammary tumors to
      PARP-1 inhibition monotherapy or combination therapy. As such, our data add
      substantial weight to the argument for the use of PARP inhibitors as therapeutic
      agents against human breast cancers in which BRCA2 is mutated. Moreover, the
      specificity that we have shown further suggests that PARP inhibitors will be
      generally effective against tumors caused by dysregulation of components of the
      homologous recombination pathway.

PMID- 19383923
TI  - A tumor-protective role for human kallikrein-related peptidase 6 in breast cancer
      mediated by inhibition of epithelial-to-mesenchymal transition.
AB  - Human kallikrein-related peptidase 6 (KLK6) was cloned as a putative class II
      tumor suppressor based on its inactivated expression in metastatic breast cancer.
      Here, we investigated the mechanism(s) underlying the silencing of KLK6 gene in
      metastatic breast cancer and its putative implications for tumor progression. We
      present evidence that tumor-specific loss of KLK6 expression is due to
      hypermethylation of specific CpGs located in the KLK6 proximal promoter.
      Methylation-dependent binding of methyl CpG-binding protein 2 and the formation
      of repressive chromatin mediated by localized histone deacetylation are critical
      components of KLK6 silencing in breast tumors. Re-expression of KLK6 in
      nonexpressing MDA-MB-231 breast tumor cells by stable cDNA transfection resulted
      in marked reversal of their malignant phenotype, manifested by lower
      proliferation rates and saturation density, marked inhibition of anchorage
      independent growth, reduced cell motility, and their dramatically reduced ability
      to form tumors when implanted in severe combined immunodeficiency mice.
      Interestingly, inhibition of tumor growth was observed at physiologic
      concentrations of KLK6, but not when KLK6 was highly overexpressed, as observed
      in a subset of breast tumors. Differential proteomic profiling revealed that KLK6
      re-expression results in significant down-regulation of vimentin which represents
      an established marker of epithelial-to-mesenchymal transition of tumor cells and
      in concomitant up-regulation of calreticulin and epithelial markers cytokeratin 8
      and 19, indicating that KLK6 may play a protective role against tumor progression
      that is likely mediated by inhibition of epithelial-to-mesenchymal transition. We
      suggest that KLK6 is an epigenetically regulated tumor suppressor in human breast
      cancer and provide ways of pharmacologic modulation.

PMID- 19383922
TI  - Synergistic activity of the SRC family kinase inhibitor dasatinib and oxaliplatin
      in colon carcinoma cells is mediated by oxidative stress.
AB  - Chemotherapeutic regimens for the treatment of colorectal cancer generally
      include oxaliplatin, although inherent and acquired resistance is common. One
      potential mediator of oxaliplatin sensitivity is the nonreceptor protein tyrosine
      kinase, Src, the activity of which correlates with disease stage and patient
      survival. Therefore, we investigated the effects of Src inhibition using the
      tyrosine kinase inhibitor dasatinib on oxaliplatin sensitivity. We show that
      oxaliplatin acutely activates Src and that combination treatment with dasatinib
      is synergistic in a cell-line dependent manner, with the level of Src activation
      correlating with extent of synergy in a panel of six cell lines. Intracellular
      reactive oxygen species (ROS) are generated after oxaliplatin treatment, and ROS
      potently activates Src. Pretreatment with antioxidants inhibits oxaliplatin
      induced Src activation. In oxaliplatin-resistant cell lines, Src activity is
      constitutively increased. In a mouse model of colorectal liver metastases,
      treatment with oxaliplatin also results in chronic Src activation. The
      combination of dasatinib and oxaliplatin results in significantly smaller tumors
      compared with single-agent treatment, corresponding with reduced proliferation
      and angiogenesis. Therefore, we conclude that oxaliplatin activates Src through a
      ROS-dependent mechanism. Src inhibition increases oxaliplatin activity both in
      vitro and in vivo. These results suggest that Src inhibitors combined with
      oxaliplatin may have efficacy in metastatic colon cancer and may provide the
      first indication of a molecular phenotype that might be susceptible to such
      combinations.

PMID- 19383924
TI  - Selective role for Mek1 but not Mek2 in the induction of epidermal neoplasia.
AB  - The Ras/Raf/Mek/Erk mitogen-activated protein kinase pathway regulates
      fundamental processes in normal and malignant cells, including proliferation,
      differentiation, and cell survival. Mutations in this pathway have been
      associated with carcinogenesis and developmental disorders, making Mek1 and Mek2
      prime therapeutic targets. In this study, we examined the requirement for Mek1
      and Mek2 in skin neoplasia using the two-step 7,12-dimethylbenz(a)anthracene/12-O
      tetradecanoylphorbol-13-acetate (DMBA/TPA) skin carcinogenesis model. Mice
      lacking epidermal Mek1 protein develop fewer papillomas than both wild-type and
      Mek2-null mice following DMBA/TPA treatment. Mek1 knockout mice had smaller
      papillomas, delayed tumor onset, and half the tumor burden of wild-type mice.
      Loss of one Mek1 allele, however, did not affect tumor development, indicating
      that one Mek1 allele is sufficient for normal papilloma formation. No difference
      in TPA-induced hyperproliferation, inflammation, or Erk activation was observed
      between wild-type, conditional Mek1 knockout, and Mek2-null mice, indicating that
      Mek1 findings were not due to a general failure of these processes. These data
      show that Mek1 is important for skin tumor development and that Mek2 cannot
      compensate for the loss of Mek1 function in this setting.

PMID- 19383925
TI  - Kit inhibitor APcK110 induces apoptosis and inhibits proliferation of acute
      myeloid leukemia cells.
AB  - Kit is a membrane-bound tyrosine kinase and receptor for stem cell factor (SCF)
      with a crucial role in hematopoiesis. Mutations of KIT occur in almost half of
      patients with core-binding factor leukemias, in which they have been associated
      with worse outcome. Development of new compounds targeting Kit may therefore hold
      promise for therapy. We investigated the activity and mechanism of action of
      APcK110, a novel Kit inhibitor, in the mastocytosis cell line HMC1.2 (KITV560G
      and KITD816V), acute myeloid leukemia (AML) lines OCIM2 and OCI/AML3 (both wild
      type), and primary samples from patients with AML. We show that (a) APcK110
      inhibits proliferation of the mastocytosis cell line HMC1.2 and the SCF
      responsive cell line OCI/AML3 in a dose-dependent manner; (b) APcK110 is a more
      potent inhibitor of OCI/AML3 proliferation than the clinically used Kit
      inhibitors imatinib and dasatinib and at least as potent as cytarabine; (c)
      APcK110 inhibits the phosphorylation of Kit, Stat3, Stat5, and Akt in a dose
      dependent fashion, showing activity of APcK110 on Kit and its downstream
      signaling pathways; (d) APcK110 induces apoptosis by cleavage of caspase-3 and
      poly(ADP-ribose) polymerase; and (e) APcK110 inhibits proliferation of primary
      AML blasts in a clonogenic assay but does not affect proliferation of normal
      colony-forming cells. Although APcK110 activity may partly depend on cytokine
      responsiveness (e.g., SCF) and not exclusively KIT mutation status, it remains a
      potent inhibitor of AML and mastocytosis cell lines and primary AML samples.
      APcK110 and similar compounds should be evaluated in clinical trials of patients
      with AML.

PMID- 19383926
TI  - Vitamin D and asthma: time for intervention?

PMID- 19383927
TI  - Vitamin d and tuberculosis: new light on a potent biologic therapy?

PMID- 19383928
TI  - Update in critical care 2008.

PMID- 19383929
TI  - Update in lung transplantation 2008.

PMID- 19383930
TI  - Screening for malignant mesothelioma--looking for the holy grail.

PMID- 19383931
TI  - Are telomere lengths of leukocytes from patients with pulmonary fibrosis really
      genetically determined?

PMID- 19383932
TI  - Long-acting beta2 agonists and inhaled corticosteroids in asthma.

PMID- 19383933
TI  - Childhood obstructive sleep apnea contributes to a leading health burden.

PMID- 19383934
TI  - Long-term efficacy and safety of TDM-assisted combination of voriconazole plus
      efavirenz in an AIDS patient with cryptococcosis and liver cirrhosis.
AB  - OBJECTIVE: To report the efficacy, tolerability, and pharmacokinetic effects of
      combined voriconazole and efavirenz treatment administered at therapeutic drug
      monitoring (TDM)-based adjusted doses to a patient with AIDS, cryptococcosis, and
      mild liver cirrhosis. CASE SUMMARY: A 40-year-old man with AIDS (hemophiliac,
      antiretroviral-naive, plasma HIV-RNA = 290,000 copies/mL, CD4+ lymphocytes = 0),
      hepatitis C virus-related liver cirrhosis (Child-Pugh class A), and cryptococcal
      meningitis was failing standard antifungal therapies. He received an antifungal
      antiretroviral combination treatment based on the association of voriconazole
      plus efavirenz. Doses of both drugs were serially adjusted based on their plasma
      concentrations, which were evaluated at steady-state of each dose combination at
      least once (week 3.1 or later) as full concentration-time profile (samples
      collected at 0, 1, 2, 3, 4, 6, 8, 12 h postdose). Adequate concentrations of
      voriconazole in both plasma and cerebrospinal fluid were obtained and target
      plasma concentrations of efavirenz were achieved at the final dose adjustment
      (voriconazole 200 mg twice daily plus efavirenz 300 mg once daily, both
      administered orally). The patient showed prompt and stable suppression of
      cryptococcosis and plasma viremia of HIV at long-term follow-up (66 wk), with no
      significant adverse events. DISCUSSION: Standard therapies for cryptococcosis in
      patients with AIDS are often not effective. Voriconazole, despite its promising
      anticryptococcal efficacy, is currently not approved for cryptococcosis therapy
      in the US and Europe, nor is it recommended for combination with efavirenz due to
      the significant pharmacokinetic interactions between the 2 compounds. Thus far,
      published studies regarding the effects of voriconazole in human cryptococcosis
      are scarce and none has described the clinical and pharmacokinetic outcomes of a
      voriconazole/efavirenz combination in patients with AIDS, either with or without
      liver cirrhosis. CONCLUSIONS: The combination of voriconazole and efavirenz at
      TDM-assisted doses may represent a valuable therapeutic option in AIDS patients
      with cryptococcosis and mild liver cirrhosis.

PMID- 19383935
TI  - Hepatitis after intravenous injection of sublingual buprenorphine in acute
      hepatitis C carriers: report of two cases of disappearance of viral replication
      after acute hepatitis.
AB  - OBJECTIVE: To report 2 cases of acute hepatitis related to intravenous
      administration of buprenorphine in hepatitis C-infected patients. CASE SUMMARY:
      Two patients, aged 33 and 50 years, respectively, who were hepatitis C virus
      (HCV) carriers were treated with sublingual buprenorphine 8 mg/day for addiction.
      Several years after initiation of buprenorphine, they were hospitalized because
      of clinical hepatitis with jaundice that developed after intravenous injection of
      buprenorphine. Serum alanine aminotransferase rose to 100 times the upper limit
      of normal (ULN) in the first patient and to 21 times the ULN in the second. As
      cofactors, the first patient had consumed alcohol, and the second patient took
      aspirin 600 mg in addition to the injection of buprenorphine 20 mg 4 days before
      the onset of jaundice. After stopping the intravenous injections, both patients
      continued sublingual buprenorphine therapy, with no relapse of hepatitis.
      Interestingly, in these 2 patients, buprenorphine-induced hepatitis was followed
      by the disappearance of HCV RNA. DISCUSSION: Most cases of hepatotoxicity related
      to buprenorphine have occurred in hepatitis C-infected patients. The main
      mechanism for buprenorphine-induced hepatitis is a mitochondrial defect,
      exacerbated by cofactors with additional potential to induce mitochondria
      dysfunction (eg, HCV, alcohol, concomitant medications). According to the Naranjo
      probability scale, buprenorphine was found to be the probable cause of acute
      hepatitis in both patients. In addition, we assessed the relationship between
      intravenous buprenorphine and acute hepatitis using 2 scales for causality
      assessment of hepatotoxicity (the Council for International Organizations of
      Medical Sciences scale and the Maria & Victorino scale). The diagnosis of
      intravenous buprenorphine-induced hepatitis was classified as probable in both
      cases. In addition, these 2 cases illustrate that acute hepatitis in a carrier of
      chronic HCV may occasionally facilitate the clearance of virus. CONCLUSIONS:
      Although buprenorphine is well tolerated when used at recommended sublingual
      doses, patients should be informed about the risk of acute hepatitis with misuse
      of the drug by the intravenous route. These cases illustrate that, in carriers of
      chronic HCV, acute hepatitis may modify the host's immunotolerance and facilitate
      clearance of the virus.

PMID- 19383936
TI  - Safety and effectiveness of varenicline in a veteran population with a high
      prevalence of mental illness.
AB  - BACKGROUND: Varenicline is a selective nicotinic receptor partial agonist used to
      aid in the process of smoking cessation. Research on varenicline's approval for
      marketing demonstrated that after 12 weeks of treatment, at least 44% of patients
      successfully quit smoking and, on average, 13% of individuals discontinued
      therapy due to an adverse drug event (ADE). Growing postmarketing data linked
      varenicline to an increase in neuropsychiatric symptoms. OBJECTIVE: To evaluate
      the safety profile, specifically psychiatric symptoms, and effectiveness of
      varenicline in a veteran population and to determine whether there is an
      association among specific baseline demographics and success rate. METHODS: The
      study was a retrospective review of a prospective performance measure involving
      veterans initiated on varenicline. Patients were contacted via telephone
      throughout treatment and at week 12 for effectiveness follow-up. Smoking history
      was obtained and medication counseling was provided. The primary endpoint was
      tobacco cessation between weeks 9 and 12 of therapy. Varenicline's safety profile
      and discontinuation rates due to ADEs were also analyzed. RESULTS: Of the 50
      patients included in the study, 30% (n = 15) successfully quit smoking and 70% (n
      = 35) failed therapy (lack of effectiveness, n = 22; intolerability, n = 13).
      Prevalence of underlying mental illness in the success group (4/15; 27%) versus
      failure group (20/35; 57%) was statistically significant (p < 0.001). All
      patients who discontinued therapy due to an increase in mood and behavioral
      changes (n = 4) had an underlying psychiatric illness. The study results
      demonstrate a lower success rate and a higher incidence of discontinuation due to
      an ADE in our veteran population compared with premarketing data. An inverse
      association was shown between psychiatric disorders and success. CONCLUSIONS:
      Cautious treatment initiation and close monitoring of veterans initiated on
      varenicline are warranted. Furthermore, the results from this study demonstrate
      the need for prospective effectiveness trials to determine the clinical
      significance of the results.

PMID- 19383937
TI  - Connecting long distance: semantic distance in analogical reasoning modulates
      frontopolar cortex activity.
AB  - Solving problems often requires seeing new connections between concepts or events
      that seemed unrelated at first. Innovative solutions of this kind depend on
      analogical reasoning, a relational reasoning process that involves mapping
      similarities between concepts. Brain-based evidence has implicated the frontal
      pole of the brain as important for analogical mapping. Separately, cognitive
      research has identified semantic distance as a key characteristic of the kind of
      analogical mapping that can support innovation (i.e., identifying similarities
      across greater semantic distance reveals connections that support more innovative
      solutions and models). However, the neural substrates of semantically distant
      analogical mapping are not well understood. Here, we used functional magnetic
      resonance imaging (fMRI) to measure brain activity during an analogical reasoning
      task, in which we parametrically varied the semantic distance between the items
      in the analogies. Semantic distance was derived quantitatively from latent
      semantic analysis. Across 23 participants, activity in an a priori region of
      interest (ROI) in left frontopolar cortex covaried parametrically with increasing
      semantic distance, even after removing effects of task difficulty. This ROI was
      centered on a functional peak that we previously associated with analogical
      mapping. To our knowledge, these data represent a first empirical
      characterization of how the brain mediates semantically distant analogical
      mapping.

PMID- 19383938
TI  - Activity energy expenditure and mobility limitation in older adults: differential
      associations by sex.
AB  - In this study, the authors aimed to determine whether higher activity energy
      expenditure, assessed by using doubly labeled water, was associated with a
      reduced decline in mobility limitation among 248 older community-dwelling US
      adults aged 70-82 years enrolled in 1998-1999. Activity energy expenditure was
      calculated as total energy expenditure (assessed over 2 weeks by using doubly
      labeled water) minus resting metabolic rate (measured with indirect calorimetry),
      with adjustment for the thermic effect of food. Across sex-specific tertiles of
      activity energy expenditure, men in the lowest activity group experienced twice
      the rate of mobility limitation as men in the highest activity group (41% (n =
      18) vs. 18% (n = 8)). Conversely, women in the lowest and highest activity groups
      exhibited similarly high rates of mobility limitation (40% (n = 16) vs. 38% (n =
      15)). After adjustment for potential confounders, men with higher activity energy
      expenditure levels continued to show reduced risk of mobility limitation (per
      standard deviation (284 kcal/day): hazard ratio = 0.61, 95% confidence interval:
      0.41, 0.92). Women showed no association (per standard deviation (226 kcal/day):
      hazard ratio = 1.34, 95% confidence interval: 0.98, 1.85). Greater energy
      expenditure from any and all physical activity was significantly associated with
      reduced risk of developing mobility limitation among men, but not among women.

PMID- 19383939
TI  - FSHD region gene 1 (FRG1) is crucial for angiogenesis linking FRG1 to
      facioscapulohumeral muscular dystrophy-associated vasculopathy.
AB  - The genetic lesion that is diagnostic for facioscapulohumeral muscular dystrophy
      (FSHD) results in an epigenetic misregulation of gene expression, which
      ultimately leads to the disease pathology. FRG1 (FSHD region gene 1) is a leading
      candidate for a gene whose misexpression might lead to FSHD. Because FSHD
      pathology is most prominent in the musculature, most research and therapy efforts
      focus on muscle cells. Previously, using Xenopus development as a model, we
      showed that altering frg1 expression levels systemically leads to aberrant muscle
      development, illustrating the potential for aberrant FRG1 levels to disrupt the
      musculature. However, 50-75% of FSHD patients also exhibit retinal vasculopathy
      and FSHD muscles have increased levels of vascular- and endothelial-related FRG1
      transcripts, illustrating an underlying vascular component to the disease. To
      date, no FSHD candidate gene has been proposed to affect the vasculature. Here,
      we focus on a role for FRG1 expression in the vasculature. We found that
      endogenous frg1 is expressed in both the developing and adult vasculature in
      Xenopus. Furthermore, expression of FRG1 was found to be essential for the
      development of the vasculature, as a knockdown of FRG1 resulted in decreased
      angiogenesis and reduced expression of the angiogenic regulator DAB2. Conversely,
      tadpoles subjected to frg1 overexpression displayed the pro-angiogenic phenotypes
      of increased blood vessel branching and dilation of blood vessels, and developed
      edemas, suggesting that their circulation was disrupted. Thus, the systemic
      upregulation of the FRG1 protein shows the potential for acquiring a disrupted
      vascular phenotype, providing the first link between a FSHD candidate gene and
      the vascular component of FSHD pathology. Overall, in conjunction with our
      previous analysis, we show that FRG1 overexpression is capable of disrupting both
      the musculature and vasculature, recapitulating the two most prominent features
      of FSHD.

PMID- 19383940
TI  - Multiple congenital malformations of Wolf-Hirschhorn syndrome are recapitulated
      in Fgfrl1 null mice.
AB  - Wolf-Hirschhorn syndrome (WHS) is caused by deletions in the short arm of
      chromosome 4 (4p) and occurs in about one per 20,000 births. Patients with WHS
      display a set of highly variable characteristics including craniofacial
      dysgenesis, mental retardation, speech problems, congenital heart defects, short
      stature and a variety of skeletal anomalies. Analysis of patients with 4p
      deletions has identified two WHS critical regions (WHSCRs); however, deletions
      targeting mouse WHSCRs do not recapitulate the classical WHS defects, and the
      genes contributing to WHS have not been conclusively established. Recently, the
      human FGFRL1 gene, encoding a putative fibroblast growth factor (FGF) decoy
      receptor, has been implicated in the craniofacial phenotype of a WHS patient.
      Here, we report that targeted deletion of the mouse Fgfrl1 gene recapitulates a
      broad array of WHS phenotypes, including abnormal craniofacial development, axial
      and appendicular skeletal anomalies, and congenital heart defects. Fgfrl1 null
      mutants also display a transient foetal anaemia and a fully penetrant diaphragm
      defect, causing prenatal and perinatal lethality. Together, these data support a
      wider role for Fgfrl1 in development, implicate FGFRL1 insufficiency in WHS, and
      provide a novel animal model to dissect the complex aetiology of this human
      disease.

PMID- 19383941
TI  - The mood stabiliser lithium suppresses PIP3 signalling in Dictyostelium and human
      cells.
AB  - Bipolar mood disorder (manic depression) is a major psychiatric disorder whose
      molecular origins are unknown. Mood stabilisers offer patients both acute and
      prophylactic treatment, and experimentally, they provide a means to probe the
      underlying biology of the disorder. Lithium and other mood stabilisers deplete
      intracellular inositol and it has been proposed that bipolar mood disorder arises
      from aberrant inositol (1,4,5)-trisphosphate [IP(3), also known as
      Ins(1,4,5)P(3)] signalling. However, there is no definitive evidence to support
      this or any other proposed target; a problem exacerbated by a lack of good
      cellular models. Phosphatidylinositol (3,4,5)-trisphosphate [PIP(3), also known
      as PtdIns(3,4,5)P(3)] is a prominent intracellular signal molecule within the
      central nervous system (CNS) that regulates neuronal survival, connectivity and
      synaptic function. By using the genetically tractable organism Dictyostelium, we
      show that lithium suppresses PIP(3)-mediated signalling. These effects extend to
      the human neutrophil cell line HL60. Mechanistically, we show that lithium
      attenuates phosphoinositide synthesis and that its effects can be reversed by
      overexpression of inositol monophosphatase (IMPase), consistent with the inositol
      depletion hypothesis. These results demonstrate a lithium target that is
      compatible with our current knowledge of the genetic predisposition for bipolar
      disorder. They also suggest that lithium therapy might be beneficial for other
      diseases caused by elevated PIP(3) signalling.

PMID- 19383942
TI  - Historical analysis of airborne beryllium concentrations at a copper beryllium
      machining facility (1964-2000).
AB  - Copper beryllium alloys are the most commonly used form of beryllium; however,
      there have been few studies assessing occupational exposure in facilities that
      worked exclusively with this alloy versus those where pure metal or beryllium
      oxide may also have been present. In this paper, we evaluated the airborne
      beryllium concentrations at a machining plant using historical industrial hygiene
      samples collected between 1964 and 2000. With the exception of a few projects
      conducted in the 1960s, it is believed that >95% of the operations used copper
      beryllium alloy exclusively. Long-term (>120 min) and short-term (<120 min)
      personal and area samples were collected during a variety of activities including
      machining of copper beryllium-containing parts, as well as finishing operations
      (e.g., deburring and polishing) and decontamination of machinery. A total of 580
      beryllium air samples were analyzed (311 personal and 269 area samples). The
      average concentration based on area samples (1964-2000) was 0.021 microg m(-3)
      (SD 0.17 microg m(-3); range 0.00012-2.5 microg m(-3)); 68.8% were below the
      analytical limit of detection (LOD). The average airborne beryllium
      concentration, based on all personal samples available from 1964 through the end
      of 2000 (n = 311), was 0.026 microg m(-3) (SD 0.059 microg m(-3); range 0.019-0.8
      microg m(-3)); 97.4% were below the LOD. Personal samples collected from
      machinists (n = 78) had an average airborne concentration of 0.021 microg m(-3)
      (SD 0.014 microg m(-3); range 0.019-0.14 microg m(-3)); 97.4% were below the LOD.
      Airborne concentrations were consistently below the Occupational Safety and
      Health Administration permissible exposure limit for beryllium (2 microg m(-3)).
      Overall, the data indicate that for machining operations involving copper
      beryllium, the airborne concentrations for >95% of the samples were below the
      contemporaneous occupational exposure limits or the 1999 Department of Energy
      action level of 0.2 microg m(-3) and, in most cases, were below the LOD.

PMID- 19383944
TI  - The cover. Spring rain, New York.

PMID- 19383945
TI  - A piece of my mind. Collateral damage.

PMID- 19383943
TI  - Estrogen and tamoxifen protect against Mn-induced toxicity in rat cortical
      primary cultures of neurons and astrocytes.
AB  - Chronic exposure to manganese (Mn) leads to a neurological disorder, manganism,
      which shares multiple common features with idiopathic Parkinson disease (IPD).
      17beta-Estradiol (E2) and some selective estrogen receptor modulators, including
      tamoxifen (TX), afford neuroprotection in various experimental models of
      neurodegeneration. However, the neuroprotective effects and mechanisms of E2/TX
      in Mn-induced toxicity have yet to be documented. Herein, we studied the ability
      of E2/TX to protect rat cortical primary neuronal and astroglial cultures from Mn
      induced toxicity. Cell viability, Western blot, and reactive oxygen species (ROS)
      generation were assessed. Results established that both E2 (10nM) and TX (1
      microM) attenuated Mn-induced toxicity. The protective effects of E2/TX were more
      pronounced in astrocytes versus neurons. The E2-mediated attenuation of Mn
      induced ROS generation in astrocytes at 6-h treatment (where no cell death was
      detected) was mediated by a classical estrogen receptor (ER) pathway and the TX
      mediated effect on Mn-induced ROS generation was not mediated via classical ER
      dependent mechanisms and likely by its antioxidant properties. The
      phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway was involved in both
      E2- and TX-induced attenuation of Mn-induced ROS formation (6 h) in astrocytes.
      Treatments with Mn for a longer duration (24 h) led to significant cell death,
      and the protective effects of E2 and TX were (1) not mediated by a classical ER
      pathway and (2) associated with activation of both mitogen-activated protein
      kinase/extracellular signal-regulated kinase and PI3K/Akt signaling pathways.
      Taken together, the results suggest that both E2 and TX offer effective
      therapeutic means for neuroprotection against Mn-induced toxicity.

PMID- 19383946
TI  - Findings on alcohol dependence point to promising avenues for targeted therapies.

PMID- 19383947
TI  - Off-label cancer drug compendia found outdated and incomplete.

PMID- 19383948
TI  - FDA expands warning on diet products.

PMID- 19383949
TI  - Equivalence of generic and brand-name drugs for cardiovascular disease.

PMID- 19383950
TI  - Equivalence of generic and brand-name drugs for cardiovascular disease.

PMID- 19383951
TI  - Equivalence of generic and brand-name drugs for cardiovascular disease.

PMID- 19383952
TI  - Outcomes of Medicare beneficiaries with ventricular assist devices.

PMID- 19383953
TI  - Outcomes of Medicare beneficiaries with ventricular assist devices.

PMID- 19383954
TI  - Outcomes of Medicare beneficiaries with ventricular assist devices.

PMID- 19383955
TI  - Rapid response team implementation and hospital mortality rates.

PMID- 19383956
TI  - Rapid response team implementation and hospital mortality rates.

PMID- 19383957
TI  - Association of physician certification and outcomes among patients receiving an
      implantable cardioverter-defibrillator.
AB  - CONTEXT: Allowing nonelectrophysiologists to perform implantable cardioverter
      defibrillator (ICD) procedures is controversial. However, it is not known whether
      outcomes of ICD implantation vary by physician specialty. OBJECTIVE: To determine
      the association of implanting physician certification with outcomes following ICD
      implantation. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study using
      cases submitted to the ICD Registry performed between January 2006 and June 2007.
      Patients were grouped by the certification status of the implanting physician
      into mutually exclusive categories: electrophysiologists, nonelectrophysiologist
      cardiologists, thoracic surgeons, and other specialists. Hierarchical logistic
      regression models were developed to determine the independent association of
      physician certification with outcomes. MAIN OUTCOME MEASURES: In-hospital
      procedural complication rates and the proportion of patients meeting criteria for
      a defibrillator with cardiac resynchronization therapy (CRT-D) who received that
      device. RESULTS: Of 111,293 ICD implantations included in the analysis, 78,857
      (70.9%) were performed by electrophysiologists, 24,399 (21.9%) by
      nonelectrophysiologist cardiologists, 1862 (1.7%) by thoracic surgeons, and 6175
      (5.5%) by other specialists. Compared with patients whose ICD was implanted by
      electrophysiologists, patients whose ICD was implanted by either
      nonelectrophysiologist cardiologists or thoracic surgeons were at increased risk
      of complications in both unadjusted (electrophysiologists, 3.5% [2743/78,857];
      nonelectrophysiologist cardiologists, 4.0% [970/24,399]; thoracic surgeons, 5.8%
      [108/1862]; P < .001) and adjusted analyses (relative risk [RR] for
      nonelectrophysiologist cardiologists, 1.11 [95% confidence interval {CI}, 1.01
      1.21]; RR for thoracic surgeons, 1.44 [95% CI, 1.15-1.79]). Among 35,841 patients
      who met criteria for CRT-D, those whose ICD was implanted by physicians other
      than electrophysiologists were significantly less likely to receive a CRT-D
      device compared with patients whose ICD was implanted by an electrophysiologist
      in both unadjusted (electrophysiologists, 83.1% [21 303/25,635];
      nonelectrophysiologist cardiologists, 75.8% [5950/7849]; thoracic surgeons, 57.8%
      [269/465]; other specialists, 74.8% [1416/1892]; P < .001) and adjusted analyses
      (RR for nonelectrophysiologist cardiologists, 0.93 [95% CI, 0.91-0.95]; RR for
      thoracic surgeons, 0.81 [95% CI, 0.74-0.88]; RR for other specialists, 0.97 [95%
      CI, 0.94-0.99]). CONCLUSIONS: In this registry, nonelectrophysiologists implanted
      29% of ICDs. Overall, implantations by a nonelectrophysiologist were associated
      with a higher risk of procedural complications and lower likelihood of receiving
      a CRT-D device when indicated compared with patients whose ICD was implanted by
      an electrophysiologist.

PMID- 19383958
TI  - Continuity of outpatient and inpatient care by primary care physicians for
      hospitalized older adults.
AB  - CONTEXT: Little is known about the extent of continuity of care across the
      transition from outpatient care to hospitalization. OBJECTIVES: To describe
      continuity of care in older hospitalized patients, change in continuity over
      time, and factors associated with discontinuity. DESIGN, SETTING, AND
      PARTICIPANTS: A retrospective cohort study of 3,020,770 hospital admissions
      between 1996 and 2006 using enrollment and claims data for a 5% national sample
      of Medicare beneficiaries older than 66 years. Data files were constructed to
      include the patients' demographic and enrollment information (denominator file)
      and claims for hospital stays (MEDPAR file) and physician services (carrier
      claims file). Characteristics of the hospitals were included in annual provider
      of services files. Being seen by a physician was defined as when a physician had
      submitted a bill for evaluation and management services for that patient. MAIN
      OUTCOME MEASURES: Percentage of patients who during hospitalization were seen by
      any outpatient physician they had visited in the year before hospitalization
      (continuity with any outpatient physician) or by their primary care physician
      (PCP) (continuity with a PCP). RESULTS: In 1996, 50.5% (95% confidence interval
      [CI], 50.3%-50.7%) of hospitalized patients were seen by at least 1 physician
      that they had visited in an outpatient setting in the prior year, and 44.3% (95%
      CI, 44.1%-44.6%) of patients with an identifiable PCP were seen by that physician
      while hospitalized. These percentages decreased to 39.8% (95% CI, 39.6%-40.0%)
      and 31.9% (95% CI, 31.6%-32.1%), respectively, in 2006. Greater absolute
      decreases in continuity with any outpatient physician between 1996 and 2006
      occurred in patients admitted on weekends (13.9%; 95% CI, 12.9%-14.7%) and those
      living in large metropolitan areas (11.7%; 95% CI, 11.1%-12.3%) and in New
      England (16.2%; 95% CI, 14.4%-18.0%). In multivariable multilevel models,
      increasing involvement of hospitalists was associated with approximately one
      third of the decrease in continuity of care between 1996 and 2006. CONCLUSION:
      Between 1996 and 2006, physician continuity from outpatient to inpatient settings
      decreased in the Medicare population.

PMID- 19383959
TI  - Access to kidney transplantation among remote- and rural-dwelling patients with
      kidney failure in the United States.
AB  - CONTEXT: US residents with end-stage renal disease (ESRD) may live far away from
      the closest transplant center, which could compromise their access to kidney
      transplantation. OBJECTIVE: To assess access to kidney transplantation as a
      function of distance from the closest transplant center or as a function of rural
      rather than urban residence. DESIGN, SETTING, AND PARTICIPANTS: Observational
      study of 699,751 adult patients with kidney failure who had initiated renal
      replacement in the United States between 1995 and 2007 and were thus placed on a
      prospective mandatory registry list. MAIN OUTCOME MEASURES: Time to placement on
      the kidney transplant waiting list and time to kidney transplantation, both
      measured at the start of renal replacement. RESULTS: During a median follow-up of
      2.0 years (range, 0.0-12.5 years), 122,785 (17.5%) patients received a kidney
      transplant. Median distance to the closest transplant center was 15 miles.
      Participants were classified into distance categories by miles from a transplant
      center with 0 to 15 miles serving as the referent category. Compared with the
      referent category, the adjusted hazard ratios of deceased or living donor
      transplantation within each category follows: 16 to 50 miles, 1.03 (95% CI, 1.02
      1.05); 51 to 100 miles, 1.11 (95% CI, 1.09-1.12); 101 to 136 miles, 1.14 (95% CI,
      1.11-1.17); 137 to 231 miles, 1.16 (95% CI, 1.13-1.20); 232 to 310 miles, 1.20
      (95% CI, 1.12-1.28); and more than 310 miles, 1.16 (95% CI, 1.09-1.23). When
      residence location was classified using rural-urban commuter areas, 79.6% of
      patients lived in urban; 10.3%, micropolitan; and 10.0%, rural areas. Compared
      with those living in metropolitan areas, the adjusted hazard ratios of deceased
      or living donor transplantation among patients residing in micropolitan
      communities was 1.13 (95% CI, 1.11-1.15) and 1.15 (95% CI, 1.13-1.18) for rural
      areas. Results were similar for both deceased donor and living donor
      transplantation and were consistent in multiple sensitivity analyses. CONCLUSION:
      Remote or rural residence was not associated with increased time to kidney
      transplantation among people treated for ESRD in the United States.

PMID- 19383961
TI  - Deep brain stimulation: avoiding the errors of psychosurgery.

PMID- 19383960
TI  - Association of maternal height with child mortality, anthropometric failure, and
      anemia in India.
AB  - CONTEXT: Prior research on the determinants of child health has focused on
      contemporaneous risk factors such as maternal behaviors, dietary factors, and
      immediate environmental conditions. Research on intergenerational factors that
      might also predispose a child to increased health adversity remains limited.
      OBJECTIVE: To examine the association between maternal height and child
      mortality, anthropometric failure, and anemia. DESIGN, SETTING, AND POPULATION:
      We retrieved data from the 2005-2006 National Family Health Survey in India
      (released in 2008). The study population constitutes a nationally representative
      cross-sectional sample of singleton children aged 0 to 59 months and born after
      January 2000 or January 2001 (n = 50 750) to mothers aged 15 to 49 years from all
      29 states of India. Information on children was obtained by a face-to-face
      interview with mothers, with a response rate of 94.5%. Height was measured with
      an adjustable measuring board calibrated in millimeters. Demographic and
      socioeconomic variables were considered as covariates. Modified Poisson
      regression models that account for multistage survey design and sampling weights
      were estimated. MAIN OUTCOME MEASURES: Mortality was the primary end point;
      underweight, stunting, wasting, and anemia were included as secondary outcomes.
      RESULTS: In adjusted models, a 1-cm increase in maternal height was associated
      with a decreased risk of child mortality (relative risk [RR], 0.978; 95%
      confidence interval [CI], 0.970-0.987; P < .001), underweight (RR, 0.971; 95% CI,
      0.968-0.974; P < .001), stunting (RR, 0.971; 95% CI, 0.968-0.0973; P < .001),
      wasting (RR, 0.989; 95% CI, 0.984-0.994; P < .001), and anemia (RR, 0.998; 95%
      CI, 0.997-0.999; P = .02). Children born to mothers who were less than 145 cm in
      height were 1.71 times more likely to die (95% CI, 1.37-2.13) (absolute
      probability, 0.09; 95% CI, 0.07-0.12) compared with mothers who were at least 160
      cm in height (absolute probability, 0.05; 95% CI, 0.04-0.07). Similar patterns
      were observed for anthropometric failure related to underweight and stunting.
      Paternal height was not associated with child mortality or anemia but was
      associated with child anthropometric failure. CONCLUSION: In a nationally
      representative sample of households in India, maternal height was inversely
      associated with child mortality and anthropometric failure.

PMID- 19383962
TI  - Management of diseases without current treatment options: something can be done.

PMID- 19383963
TI  - Toward a restorative medicine--the science of care.

PMID- 19383964
TI  - Physician credentials and ICD implantation: certified "electricians" best deal
      with electrical problems.

PMID- 19383965
TI  - JAMA patient page. Kidney transplantation.

PMID- 19383967
TI  - A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing
      monocytes, blood "resident" monocytes, and embryonic macrophages suggests common
      functions and developmental relationships.
AB  - We previously showed that Tie2-expressing monocytes (TEMs) have nonredundant
      proangiogenic activity in tumors. Here, we compared the gene expression profile
      of tumor-infiltrating TEMs with that of tumor-associated macrophages (TAMs),
      spleen-derived Gr1(+)Cd11b(+) neutrophils/myeloid-derived suppressor cells,
      circulating "inflammatory" and "resident" monocytes, and tumor-derived
      endothelial cells (ECs) by quantitative polymerase chain reaction-based gene
      arrays. TEMs sharply differed from ECs and Gr1(+)Cd11b(+) cells but were highly
      related to TAMs. Nevertheless, several genes were differentially expressed
      between TEMs and TAMs, highlighting a TEM signature consistent with enhanced
      proangiogenic/tissue-remodeling activity and lower proinflammatory activity. We
      validated these findings in models of oncogenesis and transgenic mice expressing
      a microRNA-regulated Tie2-GFP reporter. Remarkably, resident monocytes and TEMs
      on one hand, and inflammatory monocytes and TAMs on the other hand, expressed
      coordinated gene expression profiles, suggesting that the 2 blood monocyte
      subsets are committed to distinct extravascular fates in the tumor
      microenvironment. We further showed that a prominent proportion of
      embryonic/fetal macrophages, which participate in tissue morphogenesis, expressed
      distinguishing TEM genes. It is tempting to speculate that Tie2(+)
      embryonic/fetal macrophages, resident blood monocytes, and tumor-infiltrating
      TEMs represent distinct developmental stages of a TEM lineage committed to
      execute physiologic proangiogenic and tissue-remodeling programs, which can be co
      opted by tumors.

PMID- 19383966
TI  - The level of monocyte turnover predicts disease progression in the macaque model
      of AIDS.
AB  - It is widely accepted that destruction of CD4(+) T cells and viral load are the
      primary markers for immunodeficiency in HIV-1-infected humans and in simian
      immunodeficiency virus (SIV)-infected macaques. However, monocyte/macrophages are
      also important targets of HIV/SIV infection and a critical link between innate
      and adaptive immunity. We therefore examined whether changes in cells of the
      monocyte/macrophage lineage could be linked to the pathogenesis of AIDS in the
      rhesus macaque model. Here, we show that massive turnover of peripheral monocytes
      associated with death of tissue macrophages correlates with AIDS progression in
      macaques. More importantly, the level of monocyte turnover was not linked to the
      CD4(+) T-cell count and was a better predictive marker for AIDS progression than
      was viral load or lymphocyte activation. Our results show the importance of
      monocyte/macrophages in the pathogenesis of AIDS and suggest the dynamic changes
      of the monocyte/macrophages as a new marker for AIDS progression.

PMID- 19383968
TI  - IL-7 adjuvant treatment enhances long-term tumor-antigen-specific CD8+ T-cell
      responses after immunization with recombinant lentivector.
AB  - Immunization with recombinant lentivector elicits higher frequencies of tumor
      antigen-specific memory CD8+ T cells than peptide-based vaccines. This finding
      correlates with our observation that, upon recombinant lentivector immunization,
      a higher fraction of antigen-specific effector CD8+ T cells does not down
      regulate the expression of the survival/memory marker interleukin-7 receptor
      alpha chain (IL-7Ralpha). Here we show that, surprisingly, higher expression of
      IL-7Ralpha on recombinant lentivector-induced effector CD8+ T cells does not
      result in the up-regulation of survival molecules, such as Bcl-2. We thus
      hypothesized that physiologic levels of IL-7 might be limiting in vivo for
      delivering survival signals to the expanding population of effector cells. To
      test this hypothesis, we administered recombinant IL-7 during the effector phase
      of the response. We observed an up-regulation of Bcl-2 and a strong expansion of
      antigen-specific effector CD8+ T cells, and of naive CD8+ T cells. Strikingly, IL
      7 treatment elicited also a significant increase in the number of antigen
      specific memory CD8+ T cells in recombinant lentivector-immunized mice, but not
      in peptide-immunized mice. Altogether, these data show that IL-7 adjuvant
      treatment can enhance long-term antigen-specific CD8+ T-cell responses. However,
      its efficacy depends on the expression of IL-7Ralpha at the surface of effector
      CD8+ T cells.

PMID- 19383969
TI  - How I treat patients with myelodysplastic syndromes.

PMID- 19383970
TI  - Antimyeloperoxidase antibodies rapidly induce alpha-4-integrin-dependent
      glomerular neutrophil adhesion.
AB  - Patients with antineutrophil cytoplasmic antibodies (ANCAs) frequently develop
      severe vasculitis and glomerulonephritis. Although ANCAs, particularly
      antimyeloperoxidase (anti-MPO), have been shown to promote leukocyte adhesion in
      postcapillary venules, their ability to promote adhesion in the glomerular
      vasculature is less clear. We used intravital microscopy to examine glomerular
      leukocyte adhesion induced by anti-MPO. In mice pretreated with LPS, 50 microg
      anti-MPO induced LFA-1-dependent adhesion in glomeruli. In concert with this
      finding, in mice pretreated with LPS, more than 80% of circulating neutrophils
      bound anti-MPO within 5 minutes of intravenous administration. However, even in
      the absence of LPS, more than 40% of circulating neutrophils bound anti-MPO in
      vivo, a response not seen in MPO(-/-) mice. In addition, a higher dose of anti
      MPO (200 microg) induced robust glomerular leukocyte adhesion in the absence of
      LPS. The latter response was beta2-integrin independent, instead requiring the
      alpha4-integrin, which was up-regulated on neutrophils in response to anti-MPO.
      These data indicate that anti-MPO antibodies bind to circulating neutrophils, and
      can induce glomerular leukocyte adhesion via multiple pathways. Lower doses
      induce adhesion only after an infection-related stimulus, whereas higher doses
      are capable of inducing responses in the absence of an additional inflammatory
      stimulus, via alternative adhesion mechanisms.

PMID- 19383971
TI  - The histone deacetylase inhibitors LAQ824 and LBH589 do not require death
      receptor signaling or a functional apoptosome to mediate tumor cell death or
      therapeutic efficacy.
AB  - LAQ824 and LBH589 (panobinostat) are histone deacetylase inhibitors (HDACi)
      developed as cancer therapeutics and we have used the Emu-myc lymphoma model to
      identify the molecular events required for their antitumor effects. Induction of
      tumor cell death was necessary for these agents to mediate therapeutic responses
      in vivo and both HDACi engaged the intrinsic apoptotic cascade that did not
      require p53. Death receptor pathway blockade had no effect on the therapeutic
      activities of LAQ824 and LBH589; however, overexpression of Bcl-2 or Bcl-X(L)
      protected lymphoma cells from HDACi-induced killing and suppressed their
      therapeutic activities. Deletion of Apaf-1 or Caspase-9 delayed HDACi-induced
      lymphoma killing in vitro and in vivo, associated with suppression of many
      biochemical indicators of apoptosis, but did not provide long-term resistance to
      these agents and failed to inhibit their therapeutic activities. Emu-myc
      lymphomas lacking a functional apoptosome displayed morphologic and biochemical
      features of autophagy after treatment with LAQ824 and LBH589, indicating that, in
      the absence of a complete intrinsic apoptosis pathway involving apoptosome
      formation, these HDACi can still mediate a therapeutic response. Our data
      indicate that damage to the mitochondria is the key event necessary for LAQ824
      and LBH589 to mediate tumor cell death and a robust therapeutic response.

PMID- 19383972
TI  - The molecular basis of hepcidin-resistant hereditary hemochromatosis.
AB  - The interaction between the hormone hepcidin and the iron exporter ferroportin
      (Fpn) regulates plasma iron concentrations. Hepcidin binds to Fpn and induces its
      internalization and degradation, resulting in decreased iron efflux from cells
      into plasma. Fpn mutations in N144, Y64N, and C326 residue cause autosomal
      dominant disease with parenchymal iron overload, apparently due to the resistance
      of mutant Fpn to hepcidin-mediated internalization. To define the mechanism of
      resistance, we generated human Fpn constructs bearing the pathogenic mutations.
      The mutants localized to the cell surface and exported iron normally, but were
      partially or completely resistant to hepcidin-mediated internalization and
      continued to export iron despite the presence of hepcidin. The primary defect
      with exofacial C326 substitutions was the loss of hepcidin binding, which
      resulted in the most severe phenotype. The thiol form of C326 was essential for
      interaction with hepcidin, suggesting that C326-SH homology is located in or near
      the binding site of hepcidin. In contrast, N144 and Y64 residues were not
      required for hepcidin binding, but their mutations impaired the subsequent
      internalization of the ligand-receptor complex. Our observations explain why the
      mutations in C326 Fpn residue produce a severe form of hemochromatosis with iron
      overload at an early age.

PMID- 19383973
TI  - Focus Issue: demystifying mTOR signaling.
AB  - The mammalian target of rapamycin (mTOR) is a master integrator of cell energy
      state, nutrient status, and growth factor stimulation. This kinase is part of two
      distinct complexes, mTORC1 and mTORC2, and the network that regulates these two
      complexes is interconnected with distinct and overlapping inputs and outputs.
      Research published in Science Signaling has revealed new connections between
      epidermal growth factor receptors and the mTOR pathway, and new insight into the
      roles of mTOR signaling in vascular disease. The Perspectives in this issue
      highlight how new pharmacological tools and the ability to knock down the
      function of complex-specific subunits are providing new insight into the
      regulation and functions of these complexes in physiological contexts, as well as
      providing new avenues for therapeutic intervention in diseases associated with
      aberrant activity of these complexes.

PMID- 19383975
TI  - The pharmacology of mTOR inhibition.
AB  - A flurry of reports indicates that we are entering a new phase in the development
      of mammalian target of rapamycin (mTOR)-based therapies for oncology. Here, we
      summarize exciting findings regarding mTOR signaling and the outlook for mTOR
      inhibitors as tools to study the mTOR pathway and as drugs in the clinic.

PMID- 19383976
TI  - Immune regulation by rapamycin: moving beyond T cells.
AB  - The mammalian target of rapamycin (mTOR) is a multifunctional kinase that
      promotes cell growth and division in response to growth factor and nutrient
      signals. Rapamycin exerts its potent immunosuppressive effects in part through
      direct effects on antigen-specific lymphocytes; however, rapamycin also modulates
      adaptive immunity through its effects on innate immune cells, including dendritic
      cells and macrophages. Studies have established rapamycin-sensitive functions of
      mTOR, downstream of Toll-like receptors, in shaping the cytokine response of
      myeloid cells and driving the production of interferon by plasmacytoid dendritic
      cells. These findings point to new strategies for boosting or suppressing
      specific immune responses.

PMID- 19383977
TI  - Akt demoted in glioblastoma.
AB  - In glioblastomas, an Akt-independent, PTEN (phosphatase and tensin homolog
      deleted on chromosome ten)-regulated signaling pathway links EGFR (epidermal
      growth factor receptor) to the phosphorylation of TOR (target of rapamycin) and
      of the ribosomal protein S6 and to the control of cell replication. Although
      PKCalpha (protein kinase Calpha) has been identified as an essential component,
      the detailed wiring of this previously unexplored noncanonical pathway remains to
      be worked out.

PMID- 19383978
TI  - New insights into mTOR signaling: mTORC2 and beyond.
AB  - The mammalian target of rapamycin complex 2 (mTORC2) plays critical roles in
      regulating cell growth and proliferation. mTORC2 promotes the activation of the
      serum glucocorticoid-induced protein kinase (SGK). This mTOR complex also
      promotes the constitutive phosphorylation of proline-directed serine or threonine
      sites in the turn motif of Akt and protein kinase C isoforms. mTORC2 may control
      phosphorylation of the turn motif by promoting the activity of a kinase that
      targets the Ser/Thr-Pro sequence or by inhibiting the activity of a phosphatase.

PMID- 19383979
TI  - A multicenter, open-label, 24-week follow-up study for efficacy on cognitive
      function of donepezil in Binswanger-type subcortical vascular dementia.
AB  - OBJECTIVES: To evaluate the efficacy and tolerability of donepezil in patients
      with Binswanger type subcortical vascular dementia. METHODS: Patients (n = 34,
      mean age = 71.8 + 7.12) with Binswanger type subcortical vascular dementia from 8
      multicenter, according to clinical and neuroradiological working criteria, were
      selected to receive donepezil 5 mg/day (n = 2) or donepezil 10 mg/day (n = 32,
      after 5 mg/day) for 24 weeks. Our primary endpoints were change from baseline to
      weeks 12 and 24 in the Seoul Neuropsychological Screening Battery-Dementia
      version (SNSB-D) and the Korean version of neuropsychiatric inventory (K-NPI).
      RESULTS: A total of 24 patients received donepezil completed the study (mean age
      = 72.0 + 7.5 K-Mini-Mental State Examination [MMSE] = 21.0 + 5.1). After 12 weeks
      and 24 weeks, patients showed improvements in cognitive function on the SNSB-D
      compared baseline of 16.29 points at 12 weeks (P < .05) and 12.44 points at 24
      weeks (P < .05). Significant improvements were shown in only memory domain,
      immediate verbal recall and delayed recall tests. Subgroup with better cognitive
      function (SNSB-D > 100) were more effective in frontal and memory domains than
      the other subgroup (SNSB-D < 100). Withdrawal rates due to adverse events were
      very low (4.16%). CONCLUSIONS: Donepezil-treated patients with Binswanger type
      subcortical vascular dementia demonstrated significant improvement in cognition
      compared with baseline, and donepezil was well tolerated.

PMID- 19383980
TI  - Relationship between postabsorptive respiratory exchange ratio and plasma free
      fatty acid concentrations.
AB  - The relationship between overnight postabsorptive (fasting) respiratory exchange
      ratio (RER) and plasma FFA concentrations was addressed using data from three
      separate protocols, each of which involved careful control of the antecedent
      diet. Protocol 1 examined the relationship between fasting RER and the previous
      daytime RER. In Protocol 2 fasting, RER and plasma palmitate concentrations were
      measured in 29 women and 31 men (body mass index <30 kg.m(-2)). Protocol 3
      analyzed data from Nielsen et al. (Nielsen, S., Z. K. Guo, J. B. Albu, S. Klein,
      P. C. O'Brien, M. D. Jensen. 2003. Energy expenditure, sex and endogenous fuel
      availability in humans. J. Clin. Invest. 111: 981-988.) to understand how fasting
      RER and palmitate concentrations relate within individuals during four
      consecutive measurements. The results were as follows: 1) Fasting RER was
      correlated (r = 0.74, P < 0.001) with the previous day's average RER, and less so
      with RER variability. 2) Fasting RER was correlated (r = -0.39, P = 0.007) with
      fasting plasma palmitate concentrations. 3) The pattern of the RER/palmitate
      relationship was similar within individuals and between individuals; a negative
      slope was observed significantly more often than a positive slope (chi(2) test; P
      < 0.001). Our findings suggest that, despite a fixed food quotient, the slight
      departures from energy equilibrium in a controlled General Clinical Research
      Center environment can effect plasma FFA concentrations. We suggest that
      including indirect calorimetry as part of FFA metabolism studies may aid in data
      interpretation.

PMID- 19383981
TI  - Biosynthesis of phosphatidylcholine by human lysophosphatidylcholine
      acyltransferase 1.
AB  - Pulmonary surfactant is a complex of phospholipids and proteins lining the
      alveolar walls of the lung. It reduces surface tension in the alveoli, and is
      critical for normal respiration. Pulmonary surfactant phospholipids consist
      mainly of phosphatidylcholine (PC) and phosphatidylglycerol (PG). Although the
      phospholipid composition of pulmonary surfactant is well known, the enzyme(s)
      involved in its biosynthesis have remained obscure. We previously reported the
      cloning of murine lysophosphatidylcholine acyltransferase 1 (mLPCAT1) as a
      potential biosynthetic enzyme of pulmonary surfactant phospholipids. mLPCAT1
      exhibits lysophosphatidylcholine acyltransferase (LPCAT) and
      lysophosphatidylglycerol acyltransferase (LPGAT) activities, generating PC and
      PG, respectively. However, the enzymatic activity of human LPCAT1 (hLPCAT1)
      remains controversial. We report here that hLPCAT1 possesses LPCAT and LPGAT
      activities. The activity of hLPCAT1 was inhibited by N-ethylmaleimide, indicating
      the importance of some cysteine residue(s) for the catalysis. We found a
      conserved cysteine (Cys(211)) in hLPCAT1 that is crucial for its activity.
      Evolutionary analyses of the close homologs of LPCAT1 suggest that it appeared
      before the evolution of teleosts and indicate that LPCAT1 may have evolved along
      with the lung to facilitate respiration. hLPCAT1 mRNA is highly expressed in the
      human lung. We propose that hLPCAT1 is the biosynthetic enzyme of pulmonary
      surfactant phospholipids.

PMID- 19383983
TI  - Computational methods for evaluating phylogenetic models of coding sequence
      evolution with dependence between codons.
AB  - In recent years, molecular evolutionary models formulated as site-interdependent
      Markovian codon substitution processes have been proposed as means of
      mechanistically accounting for selective features over long-range evolutionary
      scales. Under such models, site interdependencies are reflected in the use of a
      simplified protein tertiary structure representation and predefined statistical
      potential, which, along with mutational parameters, mediate nonsynonymous rates
      of substitution; rates of synonymous events are solely mediated by mutational
      parameters. Although theoretically attractive, the models are computationally
      challenging, and the methods used to manipulate them still do not allow for
      quantitative model evaluations in a multiple-sequence context. Here, we describe
      Markov chain Monte Carlo computational methodologies for sampling parameters from
      their posterior distribution under site-interdependent codon substitution models
      within a phylogenetic context and allowing for Bayesian model assessment and
      ranking. Specifically, the techniques we expound here can form the basis of
      posterior predictive checking under these models and can be embedded within
      thermodynamic integration algorithms for computing Bayes factors. We illustrate
      the methods using two data sets and find that although current forms of site
      interdependent models of codon substitution provide an improved fit, they are
      outperformed by the extended site-independent versions. Altogether, the
      methodologies described here should enable a quantified contrasting of
      alternative ways of modeling structural constraints, or other site-interdependent
      criteria, and establish if such formulations can match (or supplant) site
      independent model extensions.

PMID- 19383982
TI  - Glucosamine-induced endoplasmic reticulum stress attenuates apolipoprotein B100
      synthesis via PERK signaling.
AB  - Glucosamine impairs hepatic apolipoprotein B100 (apoB100) production by inducing
      endoplasmic reticulum (ER) stress and enhancing cotranslational and
      posttranslational apoB100 degradation (Qiu, W., R. K. Avramoglu, A. C. Rutledge,
      J. Tsai, and K. Adeli. Mechanisms of glucosamine-induced suppression of the
      hepatic assembly and secretion of apolipoprotein B-100-containing lipoproteins.
      J. Lipid Res. 2006. 47: 1749-1761). Here, we report that glucosamine also
      regulates apoB100 protein synthesis via ER-stress-induced PERK activation. Short
      term (4 h) glucosamine treatment of HepG2 cells reduced both cellular (by 62%)
      and secreted apoB100 (by 43%) without altering apoB100 mRNA. Treatment with
      proteasomal inhibitors only partially prevented the suppressive effects of
      glucosamine, suggesting that mechanisms other than proteasomal degradation may
      also be involved. Glucosamine-induced ER stress was associated with a
      significantly reduced apoB100 synthesis with no significant change in
      posttranslational decay rates, suggesting that glucosamine exerted its effect
      early during apoB biosynthesis. The role of PERK and its substrate, alpha-subunit
      of eukaryotic initiation factor 2 (eIF2alpha), in the suppressive effects of
      glucosamine on apoB synthesis was then investigated. Coexpression of apoB15
      (normally resistant to intracellular degradation) with wild-type double stranded
      (ds) RNA activated protein kinase (PKR)-like endoplasmic reticulum kinase (PERK)
      in COS-7 cells resulted in a dramatic reduction in the levels of newly
      synthesized apoB15. Interestingly, cotransfection with apoB15 and a kinase
      inactive PERK mutant (K618A) increased apoB15 expression. In addition, short-term
      glucosamine treatment stimulated an increase in phosphorylation of PERK and
      eIF2alpha. Taken together, these data suggest that in addition to the induction
      of ER-associated degradation and other degradative pathways, ER stress is
      associated with suppression of apoB synthesis via a PERK-dependent mechanism.

PMID- 19383984
TI  - Hyperglycemia regulates RUNX2 activation and cellular wound healing through the
      aldose reductase polyol pathway.
AB  - Diabetes mellitus accelerates cardiovascular microangiopathies and
      atherosclerosis, which are a consequence of hyperglycemia. The aldose reductase
      (AR) polyol pathway contributes to these microvascular complications, but how it
      mediates vascular damage in response to hyperglycemia is less understood. The
      RUNX2 transcription factor, which is repressed in diabetic animals, promotes
      vascular endothelial cell (EC) migration, proliferation, and angiogenesis. Here
      we show that physiological levels of glucose (euglycemia) increase RUNX2 DNA
      binding and transcriptional activity, whereas hyperglycemia does not. However,
      inhibition of AR reverses hyperglycemic suppression of RUNX2. IGF-1 secretion and
      IGF receptor phosphorylation by autocrine IGF-1 occur equally in euglycemic or
      hyperglycemic conditions, suggesting that reduced RUNX2 activity in response to
      hyperglycemia is not because of altered IGF-1/IGF receptor activation. AR also
      negatively regulates RUNX2-dependent vascular remodeling in an EC wounded
      monolayer assay, which is reversed by specific AR inhibition in hyperglycemia.
      Thus, euglycemia supports RUNX2 activity and promotes normal microvascular EC
      migration and wound healing, which are repressed under hyperglycemic conditions
      through the AR polyol pathway.

PMID- 19383986
TI  - Control of esophageal and intragastric pH with compounded and manufactured
      omeprazole in patients with reflux esophagitis: a pilot study.
AB  - BACKGROUND: Proton pump inhibitors (PPI) are the drugs of choice for treatment of
      gastroesophageal reflux disease (GERD). Omeprazole, the first PPI commercialized,
      is now available in different formulations. OBJECTIVES: To compare the efficacy
      of different omeprazole formulations on gastric acid secretion measured by
      intragastric and esophageal pH monitoring in patients with reflux esophagitis.
      METHODS: Prospective, open, randomized clinical trial involving H. pylori
      negative patients with typical symptoms of GERD. Patients were submitted to 24-h
      intragastric and esophageal pH studies during use of six different formulations
      of compounded and manufactured omeprazole. RESULTS: Thirty patients, 19 female,
      median age 55 years were studied. The intragastric pH was maintained below 4.0
      for a median of 36.7% of total time in compounded group and 47.7% in manufactured
      group (p>0.05). There was also no statistical difference between the median
      percentage of time of pH below 4.0 in orthostatic and supine position in
      compounded and manufactured groups (30.1% and 49.6% and 28.8% and 55.2%,
      respectively). The esophageal pH was maintained below 4.0 for a median of 0.1% of
      total time in compounded group and 0.4% in manufactured group (p>0.05). In
      orthostatic position the median percentage of time of esophageal pH below 4.0 was
      0.0% in both groups (p>0.05). In supine position, the median percentage of time
      of esophageal pH below 4.0 was 0.1% and 0.3% in compounded and manufactured
      groups, respectively (p>0.05). CONCLUSION: The omeprazole formulations studied
      (compounded and manufactured) showed similar control of gastric acid secretion
      and esophageal acid exposure in patients with reflux esophagitis.

PMID- 19383985
TI  - OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1)
      deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional
      activity.
AB  - Estrogen receptor (ER) alpha is an essential component in human physiology and is
      a key factor involved in the development of breast and endometrial cancers.
      ERalpha protein levels and transcriptional activity are tightly controlled by the
      ubiquitin proteasome system. Deubiquitinating enzymes, a class of proteases
      capable of removing ubiquitin from proteins, are increasingly being seen as key
      modulators of the ubiquitin proteasome system, regulating protein stability and
      other functions by countering the actions of ubiquitin ligases. Using mass
      spectrometry analysis of an ERalpha protein complex, we identified OTU domain
      containing ubiquitin aldehyde-binding protein 1 (OTUB1) as a novel ERalpha
      interacting protein capable of deubiquitinating ERalpha in cells and in vitro. We
      show that OTUB1 negatively regulates transcription mediated by ERalpha in
      transient reporter gene assays and transcription mediated by endogenous ERalpha
      in Ishikawa endometrial cancer cells. We also show that OTUB1 regulates the
      availability and functional activity of ERalpha in Ishikawa cells by affecting
      the transcription of the ERalpha gene and by stabilizing the ERalpha protein in
      the chromatin.

PMID- 19383987
TI  - Therapeutic hypothermia for neonatal encephalopathy implications for neonatal
      units in India.
AB  - Therapeutic hypothermia has recently emerged from bench to bedside. Three large
      multicenter trials from industrialized countries and three independent meta
      analyses have shown its efficacy in reducing death and disability following
      neonatal encephalopathy due a perinatal hypoxic event. Many neonatal units in
      well-resourced settings now offer hypothermia as standard care in neonatal
      encephalopathy. However, these results cannot be extrapolated to low resource
      settings due to differences in population, risk benefits and high cost. Use of
      therapeutic hypothermia in low resource settings should be considered
      experimental and should therefore be restricted to well equipped level 2 and 3
      neonatal units. The safety and efficacy of hypothermia using novel low technology
      methods need to be examined in rigorously controlled multicenter randomized
      controlled trials in these neonatal units before it can be offered as a standard
      care, as the risks may outweigh the benefits. The current practice of maintaining
      normothermia should continue, until such evidence is available.

PMID- 19383988
TI  - Algorithmic models to predict allergic disease using multiple neonatal markers.
AB  - Childhood blindness and visual impairment are as important and perhaps more
      devastating and disabling than adult onset blindness, because of the long span of
      life still remaining to be lived. Refractive errors and more particularly myopia,
      place a substantial burden on the individual and society. School-age children
      constitute a particularly vulnerable group where uncorrected refractive errors
      may have a dramatic impact on learning capability and educational potential. This
      article provides an overview of school eye screening from the perspective of
      National Program for Control of Blindness (NPCB), Government of India; and
      challenges, future directions and thrust area envisaged under the program for
      amelioration of childhood blindness.

PMID- 19383989
TI  - Do inhaled corticosteroids adversely influence glucose metabolism.

PMID- 19383990
TI  - Influenza vaccination for children in India.

PMID- 19383991
TI  - Human rights watch 2009 world report sincere solidarity is warranted.

PMID- 19383992
TI  - Drug therapy of cardiac diseases in children.
AB  - JUSTIFICATION: The indications and doses of most drugs used for heart ailments in
      children are extrapolated from data in adult patients. Separate guidelines are
      needed for neonates, infants and children because of the differences in
      underlying heart diseases and metabolic clearance of some of these drugs.
      PROCESS: Consensus emerged following expert deliberations at the National Meeting
      on Management of Congenital Heart Diseases in India, held on 13th September 2008,
      at the All India Institute of Medical Sciences, New Delhi, India, supported by
      Pediatric Cardiac Society of India. OBJECTIVES: To review the literature and
      frame evidence based guidelines for (i) indications, doses, adverse effects and
      safety profile of commonly used drugs in pediatric cardiology practice; and (ii)
      to provide an algorithm for treatment in various clinical settings.
      RECOMMENDATIONS: Consensus review and recommendations are given for drugs used in
      children for heart failure, hypertension, thrombosis, supraventricular
      tachycardia and intensive care. Guidelines are also given for use of intravenous
      immunoglobulins and sildenafil in children.

PMID- 19383993
TI  - Prenatal diagnosis of restrictive dermopathy.
AB  - We report three cases of Restrictive dermopathy from unrelated families. All were
      small for gestational age with small eyes and open mouth. Taut, stretched skin
      caused restriction of movements. Clavicular hypoplasia was a consistent
      radiological feature. Molecular diagnosis in the parents facilitated prenatal
      diagnosis from chorionic villous sample (CVS) in the subsequent pregnancy.

PMID- 19383994
TI  - Drowning in concentrated syrup.
AB  - Drowning is one of the two leading causes of accidental death in children. Most
      of the cases can be attributed to fresh or salt water drowning. We report an
      unusual case of acute respiratory distress syndrome in a one year old child
      following drowning in concentrated sugar syrup, in whom timely intervention and
      early supportive therapy resulted in a favorable outcome.

PMID- 19383995
TI  - Juvenile Paget's disease.
AB  - Juvenile Pagets disease (JPD), a rare genetic disorder characterized by markedly
      accelerated bone turnover, presents in early childhood. We report a child with
      typical features of JPD who remained undiagnosed till 15 years of age. Rarity of
      this disease in Indian literature and need for early diagnosis to prevent
      progression of disease prompted us to report this case.

PMID- 19383996
TI  - Double aneuploidy with Down syndrome.

PMID- 19383997
TI  - Suppression of brainstem reflexes in snakebite.

PMID- 19383998
TI  - Misuse of betamethasone.

PMID- 19383999
TI  - Misuse of corticosteroids in madhya pradesh.

PMID- 19384000
TI  - In vivo dosimetry in the urethra using alanine/ESR during (192)Ir HDR
      brachytherapy of prostate cancer--a phantom study.
AB  - A phantom study for dosimetry in the urethra using alanine/ESR during (192)Ir HDR
      brachytherapy of prostate cancer is presented. The measurement method of the
      secondary standard of the Physikalisch-Technische Bundesanstalt had to be
      slightly modified in order to be able to measure inside a Foley catheter. The
      absorbed dose to water response of the alanine dosimetry system to (192)Ir was
      determined with a reproducibility of 1.8% relative to (60)Co. The resulting
      uncertainty for measurements inside the urethra was estimated to be 3.6%,
      excluding the uncertainty of the dose rate constant Lambda. The applied dose
      calculated by a treatment planning system is compared to the measured dose for a
      small series of (192)Ir HDR irradiations in a gel phantom. The differences
      between the measured and applied dose are well within the limits of uncertainty.
      Therefore, the method is considered to be suitable for measurements in vivo.

PMID- 19384001
TI  - The implication of non-cyclic intrafractional longitudinal motion in SBRT by
      TomoTherapy.
AB  - To determine the dosimetric impact of non-cyclic longitudinal intrafractional
      motion, TomoTherapy plans with different field sizes were interrupted during a
      phantom delivery, and a displacement between -5 mm and 5 mm was induced prior to
      the delivery of the completion procedure. The planar dose was measured by film
      and a cylindrical phantom, and under-dosed or over-dosed volume was observed for
      either positive or negative displacement. For a 2.5 cm field, there was a 4%
      deviation for every mm of motion and for a 1 cm field, the deviation was 8% per
      mm. The dimension of the under/over-dosed area was independent of the motion but
      dependent on the field size. The results have significant implication in small
      field high-dose treatments (i.e. stereotactic body radiation therapy (SBRT)) that
      deliver doses in only a few fractions. Our studies demonstrate that a small
      longitudinal motion may cause a dose error that is difficult to compensate;
      however, dividing a SBRT fraction into smaller passes is helpful to reduce such
      adverse effects.

PMID- 19384002
TI  - Measuring the similarity of target volume delineations independent of the number
      of observers.
AB  - The variability of target delineations is a topic of interest in radiotherapy.
      The similarity of delineations is often quantified by use of a conformity index
      (CI) defined as the ratio of common to encompassing volume. Several forms of CI
      are in use, but no consensus exists on how to calculate the CI for more than two
      delineations. This study proposes a generalization of the CI applicable to any
      number of delineations. The generalization of the CI was developed, unbiased with
      respect to the number of delineations. Numerical values were calculated for
      clinical and theoretical cases, and differences with other forms of CI were
      considered. A simple expression could be derived, applicable to any number of
      delineations, and is equivalent to the known CI for two delineations. The use of
      this index is advised, although another frequently used index obtained from
      averaging the CI between all possible pairs of delineations results in minor
      differences. The use of the third generalization for the CI which is based upon
      the volume common to all delineations shows a clear dependence upon the number of
      delineations and is discouraged.

PMID- 19384004
TI  - Detective quantum efficiency measured as a function of energy for two full-field
      digital mammography systems.
AB  - This paper presents detective quantum efficiency (DQE) data measured for a range
      of x-ray beam qualities for two full-field digital mammography (FFDM) systems: a
      caesium iodide (CsI) detector-based unit and a system designed around an
      amorphous selenium (a-Se) x-ray detector. Four beam qualities were studied for
      each system, covering mean energies from 17.8 keV to 23.4 keV for the CsI system
      and 17.8 keV to 24.7 keV for the a-Se unit. These were set using 2, 4, 6 and 7 cm
      polymethylmethacralate (PMMA) and typical tube voltage and target/filter
      combinations selected by the automatic exposure control (AEC) program used
      clinically on these systems. Normalized noise power spectra (NNPS) were
      calculated from flood images acquired at these beam qualities for a target
      detector air kerma of 100 microGy. Modulation transfer function (MTF) data were
      acquired at 28 kV and Mo/Mo target/filter setting. The DQE was then calculated
      from the MTF and NNPS results. For comparison, the quantum detective efficiency
      (QDE) and energy absorption efficiency (EAE) were calculated from tabulated
      narrow beam spectral data. With regard to detector response, some energy
      dependence was noted for pixel value plotted against air kerma at the detector.
      This amounted to a change in the gradient of the detector response of
      approximately 15% and 30% per keV for the CsI- and a-Se-based systems,
      respectively. For the DQE results, a reduction in DQE(0) of 22% was found for the
      CsI-based unit as beam quality changed from 25 kV Mo/Mo and 2 cm PMMA to 32 kV
      Rh/Rh and 7 cm PMMA. For the a-Se system, a change in beam quality from 25 kV
      Mo/Mo and 2 cm PMMA to 34 kV Mo/Rh and 7 cm PMMA led to a reduction in DQE(0) of
      8%. Comparing measured data with simple calculations, a reduction in x-ray
      quantum detection efficiency of 27% was expected for the CsI-based system, while
      a reduction of 11% was predicted for the a-Se system.

PMID- 19384003
TI  - Experimental evaluation of a robust optimization method for IMRT of moving
      targets.
AB  - Internal organ motion during radiation therapy, if not considered appropriately
      in the planning process, has been shown to reduce target coverage and increase
      the dose to healthy tissues. Standard planning approaches, which use safety
      margins to handle intrafractional movement of the tumor, are typically designed
      based on the maximum amplitude of motion, and are often overly conservative.
      Comparable coverage and reduced dose to healthy organs appear achievable with
      robust motion-adaptive treatment planning, which considers the expected
      probability distribution of the average target position and the uncertainty of
      its realization during treatment delivery. A dosimetric test of a robust
      optimization method for IMRT was performed, using patient breathing data.
      External marker motion data acquired from respiratory-gated radiotherapy patients
      were used to build and test the framework for robust optimization. The motion
      trajectories recorded during radiation treatment itself are not strictly
      necessary to generate the initial version of a robust treatment plan, but can be
      used to adapt the plan during the course of treatment. Single-field IMRT plans
      were optimized to deliver a uniform dose to a rectangular area. During delivery
      on a linear accelerator, a computer-driven motion phantom reproduced the
      patients' breathing patterns and a two-dimensional ionization detector array
      measured the dose delivered. The dose distributions from robust-optimized plans
      were compared to those from standard plans, which used a margin expansion.
      Dosimetric tests confirmed the improved sparing of the non-target area with
      robust planning, which was achieved without compromising the target coverage. The
      maximum dose in robust plans did not exceed 110% of the prescription, while the
      minimum target doses were comparable in standard and robust plans. In test
      courses, optimized for a simplified target geometry, and delivered to a phantom
      that moved in one dimension with an average amplitude of 17 mm, the robust
      treatment design produced a reduction of more than 12% of the integral dose to
      non-target areas, compared to the standard plan using 10 mm margin expansion.

PMID- 19384005
TI  - The influence of small field sizes, penumbra, spot size and measurement depth on
      perturbation factors for microionization chambers.
AB  - The purpose of this study was the investigation of perturbation factors for
      microionization chambers in small field dosimetry and the influence of penumbra
      for different spot sizes. To this purpose, correlated sampling was implemented in
      the EGSnrc Monte Carlo (MC) user code cavity: CScavity. CScavity was first
      benchmarked against results in the literature for an NE2571 chamber. An
      efficiency increase of 17 was attained for the calculation of a realistic chamber
      perturbation factor in a water phantom. Calculations have been performed for
      microionization chambers of type PinPoint 31006 and PinPoint 31016 in full
      BEAMnrc linac simulations. Investigating the physical backgrounds of the
      differences for these small field settings, perturbation factors have been split
      up into (1) central electrode perturbation, (2) wall perturbation, (3) air-to
      water perturbation (chamber volume air-to-water) and (4) water volume
      perturbation (water chamber volume to 1 mm(3) voxel). The influence of different
      spot sizes, position in penumbra, measuring depth and detector geometry on these
      perturbation factors has been investigated, in a 0.8 x 0.8 cm(2) field setting.
      p(cel) for the PP31006 steel electrode shows a variation of up to 1% in the
      lateral position, but only 0.4% for the PP31016 with an Al electrode. The air-to
      water perturbation in the optimal scanning direction for both profiles and depth
      is most influenced by the radiation field, and only to a small extent the chamber
      geometry. The PP31016 geometry (shorter, larger radius) requires less total
      perturbation within the central axis of the field, but results in slightly larger
      variations off axis in the optimal scanning direction. Smaller spot sizes (0.6 mm
      FWHM) and sharper penumbras, compared to larger spot sizes (2 mm FWHM), result in
      larger perturbation starting in the penumbra. The longer geometries of the
      PP31006/14/15 exhibit in the non-optimal scanning direction large variations in
      total perturbation (p(tot) 1.201(4) (0.6 mm spot, 3 mm off axis, type A MC
      uncertainty) to 0.803(4) (5 mm off axis)) mainly due to volume perturbation.
      Therefore in IMRT settings, when the detector is not always in the optimal
      scanning direction, the PP31016 geometry requires less extreme perturbation (max
      p(tot) 1.130(3)) and shows less variation. However, these results suggest that
      small variations in positioning, spot size or MLC result in large differences in
      perturbation factors. Therefore even these 0.016 cm(3) ionization chambers are
      limited in their use for a field setting of 0.8 x 0.8 cm(2), as used in this
      investigation.

PMID- 19384006
TI  - A functional form for injected MRI Gd-chelate contrast agent concentration
      incorporating recirculation, extravasation and excretion.
AB  - A functional form for the vascular concentration of MRI contrast agent after
      intravenous bolus injection was developed that can be used to model the
      concentration at any vascular site at which contrast concentration can be
      measured. The form is based on previous models of blood circulation, and is
      consistent with previously measured data at long post-injection times, when the
      contrast agent is fully and evenly dispersed in the blood. It allows the first
      pass and recirculation peaks of contrast agent to be modelled, and measurement of
      the absolute concentration of contrast agent at a single time point allows the
      whole time course to be rescaled to give absolute contrast agent concentration
      values. This measure of absolute concentration could be performed at a long post
      injection time using either MRI or blood-sampling methods. In order to provide a
      model that is consistent with measured data, it was necessary to include both
      rapid and slow extravasation, together with excretion via the kidneys. The model
      was tested on T(1)-weighted data from the descending aorta and hepatic portal
      vein, and on T*(2)-weighted data from the cerebral arteries. Fitting of the model
      was successful for all datasets, but there was a considerable variation in fit
      parameters between subjects, which suggests that the formation of a meaningful
      population-averaged vascular concentration function is precluded.

PMID- 19384007
TI  - Evaluation of the Delta4 phantom for IMRT and VMAT verification.
AB  - The Delta(4) diode array phantom (Scandidos, Uppsala, Sweden) was evaluated for
      verification of segmental intensity-modulated radiation therapy (IMRT) and
      volumetric modulated arc therapy (VMAT) on an Elekta linear accelerator (Crawley
      UK). The device was tested for angular sensitivity by irradiating it from 36
      different gantry angles, and the responses of the device to various step-and
      shoot segment doses and dose rates were evaluated using an ionization chamber as
      a comparison. The phantom was then compared with ionization chamber and film
      results for two prostate and pelvic nodes IMRT plans, two head and neck IMRT
      plans and two lung VMAT plans. These plans were calculated using Pinnacle(3)
      (Philips Radiation Oncology Systems, Madison, WI). The uniformity of angular
      response was better than 0.5% over the range of gantry angles. The uniformity of
      response of the Delta(4) to different segment monitor units and dose rates was
      better than 0.5%. The assessment of the IMRT and VMAT plans showed that the
      Delta(4) measured a dose within 2.5% of the ionization chamber, and compared to
      film recorded a slightly larger region (range -2% to +7%) agreeing with the
      planned dose to within 3% and 3 mm. The Delta(4) is a complex device and requires
      careful benchmarking, but following the successful completion of these
      measurements, the Delta(4) has been introduced into clinical use.

PMID- 19384008
TI  - Performance evaluation of an Inveon PET preclinical scanner.
AB  - We evaluated the performance of an Inveon preclinical PET scanner (Siemens
      Medical Solutions), the latest MicroPET system. Spatial resolution was measured
      with a glass capillary tube (0.26 mm inside diameter, 0.29 mm wall thickness)
      filled with (18)F solution. Transaxial and axial resolutions were measured with
      the source placed parallel and perpendicular to the axis of the scanner. The
      sensitivity of the scanner was measured with a (22)Na point source, placed on the
      animal bed and positioned at different offsets from the center of the field of
      view (FOV), as well as at different energy and coincidence windows. The noise
      equivalent count rates (NECR) and the system scatter fraction were measured using
      rat-like (Phi = 60, L = 150 mm) and mouse-like (Phi = 25 mm, L = 70 mm)
      cylindrical phantoms. Line sources filled with high activity (18)F (>250 MBq)
      were inserted parallel to the axes of the phantoms (13.5 and 10 mm offset). For
      each phantom, list-mode data were collected over 24 h at 350-650 keV and 250-750
      keV energy windows and 3.4 ns coincidence window. System scatter fraction was
      measured when the random event rates were below 1%. Performance phantoms
      consisting of cylinders with hot rod inserts filled with (18)F were imaged. In
      addition, we performed imaging studies that show the suitability of the Inveon
      scanner for imaging small structures such as those in mice with a variety of
      tracers. The radial, tangential and axial resolutions at the center of FOV were
      1.46 mm, 1.49 and 1.15 mm, respectively. At a radial offset of 2 cm, the FWHM
      values were 1.73, 2.20 and 1.47 mm, respectively. At a coincidence window of 3.4
      ns, the sensitivity was 5.75% for EW = 350-650 keV and 7.4% for EW = 250-750 keV.
      For an energy window of 350-650 keV, the peak NECR was 538 kcps at 131.4 MBq for
      the rat-like phantom, and 1734 kcps at 147.4 MBq for the mouse-like phantom. The
      system scatter fraction values were 0.22 for the rat phantom and 0.06 for the
      mouse phantom. The Inveon system presents high image resolution, low scatter
      fraction values and improved sensitivity and count rate performance.

PMID- 19384009
TI  - Why learn research methodology?

PMID- 19384010
TI  - Advances in pharmacological strategies for the prevention of cataract
      development.
AB  - Cataractous-opacification of the lens is one of the leading causes of blindness
      in India. The situation can be managed by surgical removal of the cataractous
      lens. Various pharmacological strategies have been proposed for the prevention
      and treatment of cataract. Information on possible benefits of putative
      anticataract agents comes from a variety of approaches, ranging from laboratory
      experiments, both in vitro and in vivo , to epidemiological studies in patients.
      This review deals with the various mechanisms, and possible pharmacological
      interventions for the prevention of cataract. The article also reviews research
      on potential anticataractous agents, including aldose reductase inhibitors,
      glutathione boosters, antiglycating agents, vitamins and various drugs from
      indigenous sources.

PMID- 19384011
TI  - Preventive effect of onion juice on selenite-induced experimental cataract.
AB  - PURPOSE: To evaluate the effects of onion juice on sodium-selenite induced
      cataract formation. MATERIALS AND METHODS: Thirty-two 10-day-old Wistar-albino
      rat pups were divided into four equal groups. Group 1 received only subcutaneous
      saline injection. In Group 2, sodium-selenite (30 nmol / g body weight) was
      injected subcutaneously. In Group 3, subcutaneous sodium-selenite was injected
      and one drop 50% diluted fresh juice of crude onion was instilled every 8 h into
      the right eye for 14 days; the left eye received no treatment. Group 4 rats were
      similar to those of Group 3, the only difference being that of undiluted fresh
      juice of crude onion. The development of cataract was assessed. Rat lenses were
      analyzed for total antioxidant (TA) level, and for activities of glutathione
      peroxidase (GPX) and superoxide dismutase (SOD). RESULTS: Both eyes of all rats
      in Group 1 did not exhibit cataract formation . In Group 2, all rats developed
      Grade 3 cataract in the lenses of both eyes. The difference in exhibited cataract
      in the lens of the right eyes in all rats between Group 2 and any eyes of groups
      3 or 4 were significant ( P = 0.001). The mean TA level and mean activities of
      SOD and GPX in Group 2 rat lenses were significantly lower than the values in
      lenses of all rats in Group 1 ( P = 0.001, 0.003, 0.001), and in the lenses of
      the right eyes of rats in Groups 3 and 4 ( P = 0.001, 0.020, 0.001). CONCLUSION:
      Instillation of onion juice into the rat eyes can effectively prevent selenite
      induced cataract formation. This effect was associated with increased TA level,
      SOD and GPX activities in the lens.

PMID- 19384012
TI  - Comparison between Ringer's lactate and balanced salt solution on postoperative
      outcomes after phacoemulsfication: a randomized clinical trial.
AB  - AIM: To compare the effects of balanced salt solution (BSS) and Ringer's lactate
      (RL) on corneal thickness, endothelial morphology, and postoperative anterior
      chamber inflammation in eyes undergoing phacoemulsification. SETTING: Iladevi
      cataract and IOL research center, Ahmedabad, India. MATERIALS AND METHODS: This
      prospective randomized study comprised 90 consecutive patients with age-related
      cataract who were randomly assigned to either Group 1 (n = 45) with BSS or Group
      2 (n = 45) with RL. Observations made included measurement of central corneal
      thickness (CCT), presence of anterior chamber flare and cells, endothelial cell
      loss, and change in coefficient of variation (CV). Data was analyzed using Mann
      Whitney test and test of proportion. RESULTS: Mean increase in CCT on
      postoperative Day 1 was 58microm and 97microm in Groups 1 and 2 respectively ( P
      = 0.01). Increase in CCT at one month was 10microm and 11microm in Groups 1 and 2
      respectively ( P = 0.99); increase in CCT at three months was 3microm and 6microm
      in Groups 1 and 2 respectively ( P = 0.86). Number of eyes with flare grades in a
      range of 0 to 3 was statistically higher in Group 2 on postoperative Day 1 ( P =
      0.004, 0.016, < 0.001, 0.047 for Grade 0, 1, 2 and 3 respectively). Number of
      eyes with cells of Grade 3 on first postoperative day was significantly higher in
      Group 2 as compared to Group 1 ( P = 0.004). Three months postoperatively,
      endothelial cell loss was 5.5% and 7.8% in Groups 1 and 2 ( P = 0.21) and change
      in CV was 3 and 5.4 in Groups 1 and 2 ( P = 0.20) respectively. CONCLUSION: BSS
      offers a significant advantage over RL in terms of increase in corneal thickness
      and postoperative inflammation on the first postoperative day in patients
      undergoing phacoemulsification.

PMID- 19384013
TI  - Analysis of single nucleotide polymorphisms of CRYGA and CRYGB genes in control
      population of western Indian origin.
AB  - AIM: Polymorphisms in gamma-crystallins ( CRYG ) can serve as markers for lens
      differentiation and eye disorders leading to cataract. Several investigators have
      reported the presence of sequence variations within crystallin genes, with or
      without apparent effects on the function of the proteins both in mice and humans.
      Delineation of these polymorphic sites may explain the differences observed in
      the susceptibility to cataract observed among various ethnic groups. An easier
      Restriction Fragment Length Polymorphism (RFLP)-based method has been used to
      detect the frequency of four single nucleotide polymorphisms (SNPs) in CRYGA /
      CRYGB genes in control subjects of western Indian origin. MATERIALS AND METHODS:
      A total of 137 healthy volunteers from western India were studied. Examination
      was performed to exclude volunteers with any ocular defects. Polymerase chain
      reaction (PCR)-RFLP based method was developed for genotyping of G198A (Intron
      A), T196C (Exon 3) of CRYGA and T47C (Promoter), G449T (Exon 2) of CRYGB genes.
      RESULTS: The exonic SNPs in CRYGA and CRYGB were found to have an allele
      frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non
      coding SNP in CRYGA was 0.72. Allele frequency of T90C of CRYGB varied
      significantly ( P = 0.02) among different age groups. An in-silico analysis
      reveals that this sequence variation in CRYGB promoter impacts the binding of two
      transcription factors, ACE2 (Member of CLB2 cluster) and Progesterone Receptor
      (PR) which may impact the expression of CRYGB gene. CONCLUSIONS: This study
      establishes baseline frequency data for four SNPs in CRYGA and CRYGB genes for
      future case control studies on the role of these SNPs in the genetic basis of
      cataract.

PMID- 19384014
TI  - p53 expression in pterygium in two climatic regions in Turkey.
AB  - PURPOSE: To assess accumulation of p53 protein in samples of primary pterygium
      from people living in two different climatic regions in Turkey. MATERIALS AND
      METHODS: Group 1 included 101 pterygium specimens from people in Adana located in
      southern Turkey. Group 2 included 39 pterygium specimens from people in Ankara,
      located in the middle of Turkey. Climatic conditions throughout the year are
      sunnier and warmer in Adana than they are in Ankara. The control group (Group 3)
      included 30 specimens of conjunctiva that had been excised during cataract
      surgery from 30 patients without pterygium. The pterygial specimens and control
      conjunctiva were studied by immunohistochemistry using antibodies against p53
      protein. Pearson's chi-square test was used to compare the p53 immunoreactivity.
      RESULTS: The p53 immunoreactivity in Groups 1 and 2 was greater than it was in
      the control group ( P 0.001). There were no differences in p53 immunoreactivity
      between Groups 1 and 2 ( P= 0.060). CONCLUSION: The p53 immunoreactivity was not
      correlated with ultraviolet irradiation exposure. The p53 immunoreactivity in our
      pterygium specimens suggests that pterygium could be a result of uncontrolled
      cell proliferation.

PMID- 19384015
TI  - Comparison of Humphrey MATRIX and Swedish interactive threshold algorithm
      standard strategy in detecting early glaucomatous visual field loss.
AB  - PURPOSE: The aim of this study was to compare the Humphrey MATRIX visual field
      (frequency doubling technology threshold) and Swedish interactive threshold
      algorithm (SITA) standard strategy white on white perimetry in detecting
      glaucomatous visual field loss. MATERIAL AND METHODS: Twenty-eight adult
      subjects, diagnosed to have glaucoma at a tertiary eye care hospital, who
      fulfilled the inclusion criteria, were included in this prospective study. All
      subjects underwent a complete ophthalmic examination. Subjects with glaucomatous
      optic disc changes underwent repeat perimetric examination on the same day with
      the Humphrey visual field analyzer (HFA II) and Humphrey MATRIX, the order of
      testing being random. Only reliable fields, where the HFA results corresponded to
      the disc changes were considered for analysis. A cumulative defect depth in each
      hemifield in both HFA and MATRIX reports was calculated. RESULTS: Thirty-seven
      eyes of 24 subjects had reliable fields corresponding to optic disc changes. The
      mean age of the subjects was 56 +/- 12 years. There were 12 males and 12 females.
      The test duration was significantly less on the MATRIX, mean difference in test
      duration was -81 +/- 81.3 sec ( p p = 0.55, p = 0.64 respectively) and a positive
      correlation coefficient of 0.63 and 0.72 respectively. Poor agreement was found
      with the glaucoma hemifield test. CONCLUSION: The Humphrey MATRIX takes less time
      in performing the test than SITA Standard and shows good correlation for mean
      deviation and pattern standard deviation. However, the glaucoma hemifield test
      showed poor agreement. The Humphrey MATRIX diagnoses were similar to established
      perimetric standards.

PMID- 19384016
TI  - Validation of scoring system for preoperative stratification of intra-operative
      risks of complications during cataract surgery: Indian multi-centric study.
AB  - AIM: To validate a system that uniformly and objectively assesses the risk of
      complications of cataract surgery performed with phacoemulsification technique in
      individual patients preoperatively. MATERIALS AND METHODS: Outcome analysis of
      patient data entered into a standardized protocol. The data sheet was analyzed at
      a single center in terms of the risk assessed preoperatively and the incidence of
      surgical complications. This study did not assess the final visual outcome of
      eyes with complications. Each patient was categorized into a risk group according
      to the number of points scored. Group 1 (no added risk) 0 points, Group 2 (low
      risk) 1-2 points, Group 3 (moderate risk) 3-5 points, Group 4 (high risk) 6
      points or more. RESULTS: The number of eyes in each risk group was 2894 in Group
      1 (44.1%), 1881 in Group 2 (28.6%), 1575 in Group 3 (23.9%), and 214 in Group 4
      (3.3%). A total of 6564 eyes were assessed, of these 3669 eyes (55.9%) had a
      minimum of one risk factor and were thus not "routine". The group-specific events
      of complications were Group 1, 46 (1.6%), Group 2, 108 (5.7%), Group 3, 168
      (10.7%), and Group 4, 69 (32.2%). The total incidence of complications was 5.7%.
      The group-specific rate of intraoperative complications increased through the
      risk groups ( P < 0.001). CONCLUSION: The study validates a scoring system that
      is predictive of intraoperative complications. This system uses information that
      is readily available from the preoperative history and assessment of the patient.

PMID- 19384017
TI  - Likelihood ratios: clinical application in day-to-day practice.
AB  - In this article we provide an introduction to the use of likelihood ratios in
      clinical ophthalmology. Likelihood ratios permit the best use of clinical test
      results to establish diagnoses for the individual patient. Examples and step-by
      step calculations demonstrate the estimation of pretest probability, pretest
      odds, and calculation of posttest odds and posttest probability using likelihood
      ratios. The benefits and limitations of this approach are discussed.

PMID- 19384019
TI  - Pulsating enophthalmos in association with an orbital varix.
AB  - We report a case of pulsating enophthalmos secondary to orbital varix associated
      with orbital bony defects. A 64-year-old female with pulsating enophthalmos of
      the right eye was found to have a right orbital mass with bony defects of the
      orbit. Valsalva maneuver failed to induce proptosis. The diagnosis of orbital
      varix was confirmed by exploratory orbitotomy. During general anesthesia for
      orbitotomy, proptosis of the right eye was noted. Ophthalmologists should be
      aware of the association between orbital varices and cranial bony defects and
      encephaloceles. Proptosis induced by general anesthesia and positive pressure
      ventilation suggests an underlying distensible venous anomaly.

PMID- 19384018
TI  - Uveal melanoma presenting as cataract and staphyloma.
AB  - Blind eyes can harbor a choroidal melanoma. We report a case of uveal melanoma
      presenting as staphyloma and complicated cataract in a 45-year-old female. The
      left eye was blind for six months. She underwent comprehensive ocular examination
      but fundus examination was precluded due to total cataract. The ultrasound of the
      eye showed a large mass filling the superior, nasal and inferonasal vitreous
      cavity with high surface reflectivity and low to moderate internal reflectivity.
      Magnetic resonance imaging (MRI) confirmed the diagnosis of choroidal melanoma.
      The patient underwent extended enucleation and histopathology was consistent with
      uveal melanoma.

PMID- 19384020
TI  - Visual function and ocular status of children with hearing impairment in Oman: a
      case series.
AB  - Visual functions of children with hearing disability were evaluated in a school
      of Muscat, Oman in 2006. Two hundred and twenty-three children were tested for
      near vision, distant vision, contrast sensitivity, color vision, field of vision,
      motion perception and crowding. Profound and severe hearing loss was noted in 161
      and 63 students respectively. Thirty-five (81%) students with refractive error
      were using spectacles. Color vision and field of vision was defective in one
      student each. In 286 (64.1%) eyes, contrast sensitivity was defective. Abnormal
      contrast sensitivity was not associated with the severity of hearing loss [RR =
      1.04 (95% CI 0.91 to 1.29)]. Children with hearing impairment should be assessed
      for visual functions. Refractive error and defect in contrast sensitivity were
      unusually high among these children. In addition to visual aids, we recommend
      environmental changes to improve illumination and contrast to improve the quality
      of life of such children with double disability.

PMID- 19384021
TI  - Late corneal edema due to retained foldable lens fragment.
AB  - Late onset of corneal edema after cataract surgery is an unusual complication. We
      report a case of corneal edema presenting one month after cataract surgery.
      During implantation of the foldable lens, one haptic of the intraocular lens
      fractured at the optic haptic junction. This caused lens decentration,
      necessitating an intraocular lens exchange ten days later. The patient was
      recovering well but presented again two weeks later with a drop in vision due to
      corneal edema. A retained haptic of the intraocular lens was seen in the inferior
      anterior chamber angle. After surgical removal of the retained haptic the corneal
      edema fully resolved. Retained intraocular lens fragments can cause corneal
      endothelial damage, which may be reversible with an early diagnosis and
      intervention.

PMID- 19384022
TI  - Ocular toxicity by latex of Calotropis procera (Sodom apple).
AB  - We report the spectrum of ocular toxicity following accidental inoculation of
      latex of Calotropis procera (Sodom apple) in 29 eyes between January 2003 and
      December 2006. All patients presented with sudden painless dimness of vision with
      photophobia. Twenty-five (86%) patients had initial visual acuity of less than
      20/60. All eyes had conjunctival congestion and mild to severe corneal edema with
      Descemet's folds. Three (10%) eyes had an epithelial defect, nine (31%) had
      iridocyclitis, and seven (24%) had associated secondary glaucoma. After treatment
      with topical corticosteroids, antiglaucoma agents, cycloplegics, hypertonic
      saline and tears supplements, 27 (93%) eyes recovered completely within 3-14
      days. After three months, 17 (74%) out of 23 eyes showed a significant low
      endothelial cell count compared to the normal fellow eye ( P 0.001). The latex of
      Calotropis procera causes significant ocular morbidity which may be preventable
      by simple health education. The long-term effect on corneal endothelium has to be
      studied further.

PMID- 19384023
TI  - Aicardi syndrome: the importance of an ophthalmologist in its diagnosis.
AB  - Aicardi syndrome is a rare genetic disorder. The salient features of this
      syndrome include agenesis of corpus callosum, chorioretinal lacunae and infantile
      spasms. Of these three, chorioretinal lacunae is the most constant feature
      present. This case highlights the importance of fundus findings by an
      ophthalmologist in making the diagnosis of this rare syndrome.

PMID- 19384024
TI  - Scheimpflug imaging of pediatric posterior capsule rupture.
AB  - We report a case of an 11-year-old boy who presented two days after blunt trauma
      to the left eye with a slingshot. On examination his best corrected visual acuity
      (BCVA) was 20/20 in the right eye and 20/400 in the left eye. Slit-lamp
      examination of the left eye revealed a Vossius ring, traumatic cataract,
      traumatic posterior capsule tear (PCT). The contour of the posterior capsule
      bulge corresponded to the edges of the PCT. Rotating Scheimpflug imaging
      (Pentacam 70700:Oculus, Wetzlar Germany) confirmed the traumatic cataract in the
      region of the PCT visualized as increased lens density at the cortex-vitreous
      interface. The extent of the PCT in the greatest and least dimensions was
      documented before and after intraocular lens (IOL) implantation. Intra
      operatively, the PCT was evident and phaco-emulsification with an IOL implant was
      performed. Postoperatively, his BCVA improved to 20/20 in the left eye with a
      well-centered in-the-bag IOL as found on slit-lamp and Scheimpflug images.

PMID- 19384025
TI  - Solitary fibrous tumor of the orbit presenting in pregnancy.
AB  - A 32-year-old woman, three months pregnant, reported with the complaint of
      protrusion of the right eye for six months. She gave history of rapid protrusion
      of eyeball for the last two months along with the history of double vision for
      the last one month. Computer tomography (CT) scan revealed a well-defined mass
      lesion in the intraconal space of the right orbit which was excised through a
      lateral orbitotomy approach. Histological examination and immunohistochemistry
      revealed a solitary fibrous tumor, which showed a rapid progression in pregnancy.

PMID- 19384026
TI  - Combined photodynamic therapy and intravitreal bevacizumab as primary treatment
      for subretinal neovascularization associated with type 2 idiopathic macular
      telangiectasia.

PMID- 19384027
TI  - Bilateral periorbital ecchymosis in a case with dengue fever.

PMID- 19384028
TI  - Comparison of single injection of intravitreal triamcinolone versus single
      injection of intravitreal bevacizumab in macular edema secondary to branch
      retinal vein occlusions with regard to changes in best corrected visual acuity
      and central macular thickness in the short term.

PMID- 19384029
TI  - Laboratory microbiology to clinical microbiology: are we ready for a transition?

PMID- 19384030
TI  - Histopathology for the diagnosis of infectious diseases.
AB  - Histopathological examination of tissue biopsies for the identification of
      infectious organisms is a very important diagnostic tool. Conventional culture
      confirmation of tissue biopsies often fail to identify any pathogen as, first of
      all, invariably most of the tissue samples that are collected and sent for
      culture isolation are inappropriately collected in formalin, which prevents
      pathogen growth in culture media. Inadequate processing like grinding, etc.
      further hinders isolation. Presence of inhibitors like dead tissue debris,
      fibers, etc. also delays isolation. Microbiologists often lack expertise in
      identifying infectious pathogens directly from tissue biopsies by microscopic
      visualization. This review therefore acquaints microbiologists with the various
      methods available for detecting infectious agents by using histological stains.
      On histopathological examination of the tissue biopsy once, it is determined that
      a disease is likely to be due to an infection and has characterized the
      inflammatory response and hence associated microorganisms should be thoroughly
      looked for. Although some microorganisms or their cytopathic effects may be
      clearly visible on routine haematoxylin- and eosin-stained sections, additional
      histochemical stains are often needed for their complete characterization. Highly
      specific molecular techniques, such as immunohistochemistry, in situ
      hybridization and nucleic acid amplification, may be needed in certain instances
      to establish the diagnosis of infection. Through appropriate morphologic
      diagnoses and interlaboratory communication and collaboration, direct microscopic
      visualization of tissue samples can thus be very helpful in reaching a correct
      and rapid diagnosis.

PMID- 19384031
TI  - Role of azithromycin against clinical isolates of family enterobacteriaceae: A
      comparison of its minimum inhibitory concentration by three different methods.
AB  - PURPOSE: To determine the effect of azithromycin, a new azalide antibiotic, on
      clinical isolates of the family Enterobacteriaceae and to determine and compare
      its minimum inhibitory concentration (MIC) by disk diffusion, agar dilution and E
      test methods. MATERIALS AND METHODS: One hundred fifty-nine bacterial strains
      belonging to the family Enterobacteriaceae, isolated from different clinical
      samples, were tested for their susceptibility to azithromycin by disk diffusion,
      agar dilution and E-test methods. The MIC values were analysed and the
      percentages of agreement between the different methods were mentioned. RESULTS:
      Of the 159 isolates of the family Enterobacteriaceae, 60.37% were E. coli
      followed by Klebsiella species 28.3%, Salmonella and Shigella species 3.77% and
      Enterobacter and Citrobacter species 1.88% each. Maximum isolates were obtained
      from urine 117/159 (73.58%). Azithromycin was found to be more active against
      Salmonella and Shigella species, showing 100% sensitivity the by E-test and
      83.33% by the disk diffusion methods. In the agar dilution method, 83.33% of
      Salmonella and 66.66% of Shigella species were sensitive to azithromycin. The
      overall agreement between disk diffusion and agar dilution method was 96.8%,
      between agar dilution and E-test was 88% and between disk diffusion and E-test
      was 91.2%. CONCLUSION: Azithromycin may become an important addition to our
      antimicrobial strategies, especially for the treatment of bacterial diarrhoea and
      infections caused by Salmonella typhi.

PMID- 19384032
TI  - Quantitation of hepatitis B virus DNA in plasma using a sensitive cost-effective
      "in-house" real-time PCR assay.
AB  - BACKGROUND: Sensitive nucleic acid testing for the detection and accurate
      quantitation of hepatitis B virus (HBV) is necessary to reduce transmission
      through blood and blood products and for monitoring patients on antiviral
      therapy. The aim of this study is to standardize an "in-house" real-time HBV
      polymerase chain reaction (PCR) for accurate quantitation and screening of HBV.
      MATERIALS AND METHODS: The "in-house" real-time assay was compared with a
      commercial assay using 30 chronically infected individuals and 70 blood donors
      who are negative for hepatitis B surface antigen, hepatitis C virus (HCV)
      antibody and human immunodeficiency virus (HIV) antibody. Further, 30 HBV
      genotyped samples were tested to evaluate the "in-house" assay's capacity to
      detect genotypes prevalent among individuals attending this tertiary care
      hospital. RESULTS: The lower limit of detection of this "in-house" HBV real-time
      PCR was assessed against the WHO international standard and found to be 50 IU/mL.
      The interassay and intra-assay coefficient of variation (CV) of this "in-house"
      assay ranged from 1.4% to 9.4% and 0.0% to 2.3%, respectively. Virus loads as
      estimated with this "in-house" HBV real-time assay correlated well with the
      commercial artus HBV RG PCR assay ( r = 0.95, P < 0.0001). CONCLUSION: This assay
      can be used for the detection and accurate quantitation of HBV viral loads in
      plasma samples. This assay can be employed for the screening of blood donations
      and can potentially be adapted to a multiplex format for simultaneous detection
      of HBV, HIV and HCV to reduce the cost of testing in blood banks.

PMID- 19384033
TI  - Molecular typing of methicillin-resistant Staphylococcus aureus strains by PCR
      RFLP of SPA gene: a reference laboratory perspective.
AB  - PURPOSE: To characterize methicillin-resistant Staphylococcus aureus (MRSA)
      strains by molecular typing based on polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) of spa gene and to assess the utility of
      spa genotyping over bacteriophage typing in the discrimination of the strains.
      MATERIALS AND METHODS: Studies were undertaken on 125 MRSA strains representing
      the most predominant phage types and the non phage typeable strains. Strains were
      typed by bacteriophage typing and PCR-RFLP of spa gene. DNA sequence analysis of
      the amplified spa gene fragment of the representative RFLP patterns was performed
      using standard protocols. RESULTS: All the strains resistant to oxacillin were
      found to contain mec A gene. Fifty-two per cent of these strains were typeable by
      the international basic set of 23 phages. Five different PCR-RFLP patterns were
      observed among 125 MRSA strains. Non phage typeable strains were differentiated
      into four PCR-RFLP patterns. Sequencing of the spa gene from the representative
      strains of each RFLP pattern confirmed the length of these restriction fragments
      due to variation in the 24 bp and the 174 bp tandem repeats. It also revealed the
      presence of three new spa repeat patterns. CONCLUSION: The study demonstrates the
      importance of spa genotyping in the discrimination of MRSA strains, which were
      otherwise indistinguishable by bacteriophage typing. spa genotyping allowed
      differentiation of strains within a particular phage type. Nucleotide sequencing
      of isolates of different PCR-RFLP patterns indicated a correlation between the
      RFLP patterns of a variable number of tandem repeats and the phage type. The
      study provides valuable information on the epidemiological characterization of
      MRSA strains.

PMID- 19384034
TI  - Paragonimus heterotremus infection in Nagaland: A new focus of Paragonimiasis in
      India.
AB  - PURPOSE: To determine the prevalence of paragonimiasis among the patients who
      were attending the tuberculosis (TB) clinics at the Community Health Centre,
      Pfutsero, Phek District, Nagaland. To determine the species of Paragonimus that
      cause infection in humans and the crustacean host that acts as the infectious
      source for humans. MATERIALS AND METHODS: Sputum specimens were examined
      microscopically for Paragonimus eggs and acid fast bacilli. Blood samples were
      tested by microenzyme-linked immunosorbant assay for Paragonimus-specific
      immunoglobulin G antibodies. Crab extracts prepared by digestion with artificial
      gastric juice were examined for Paragonimus metacercariae under a stereoscopic
      microscope. The species identification of the parasite was based on morphological
      and molecular characterizations of eggs and metacercariae employing polymerase
      chain reaction and DNA sequencing. RESULTS: Seven out of the 14 patients tested
      seropositive for paragonimiasis and Paragonimus eggs were detected in sputum of
      two out of the seven seropositive patients, indicating a prevalence of 50% and an
      egg detection rate of 14%, respectively. The prevalence was highest in the 10-30
      year age group. More males got the infection than females, the ratio being 5:2.
      P. heterotremus was identified as the causative agent of human paragonimiasis and
      Potamiscus manipurensis as the crab host. CONCLUSIONS: The study revealed that
      paragonimiasis has been endemic in Pfutsero, Nagaland, and half of the patients
      attending the TB clinic were actually suffering from pulmonary paragonimiasis.
      This is the first confirmed report of an endemic focus of paragonimasis and
      description of P. heterotremus as the causative agent in Nagaland, India.

PMID- 19384035
TI  - Identification of lysine positive non-fermenting gram negative bacilli
      (Stenotrophomonas maltophilia and Burkholderia cepacia complex).
AB  - BACKGROUND: The Burkholderia cepacia complex (BCC) and Stenotrophomonas
      maltophilia are closely related groups of non-fermenting gram-negative bacilli
      (NFGNBs) having a similar spectrum of infections ranging from superficial to deep
      seated and disseminated infections. Identification of these lysine decarboxylase
      positive NFGNBs lags behind in most Indian laboratories. A simplified
      identification scheme was devised for these two pathogens that allowed us to
      isolate them with an increasing frequency at our tertiary care institute.
      MATERIALS AND METHODS: A simple five-tube conventional biochemical identification
      of these bacteria has been standardized. In the beginning, some of the isolates
      were confirmed from the International B. cepacia Working group, Belgium.
      Molecular identification and typing using recA polymerase chain reaction
      restriction fragment length polymorphism was also standardized for BCC. For short
      term preservation of BCC, an innovative method of preserving the bacteria in
      Robertson's cooked medium tubes kept in a domestic refrigerator was developed.
      RESULTS: Thirty-nine isolates of BCC isolates were obtained from various
      specimens (30 from blood cultures) and 22 S. maltophilia (13 blood cultures and 9
      respiratory isolates) were isolated during the year 2007 alone. CONCLUSIONS: BCC
      and S. maltophilia can be identified with relative ease using a small battery of
      biochemical reactions. Use of simplified methods will allow greater recognition
      of their pathogenic potential and correct antimicrobials should be advised in
      other clinical laboratories and hospitals.

PMID- 19384036
TI  - Clinical evaluation of the mycobacteriophage-based assay in rapid detection of
      Mycobacterium tuberculosis in respiratory specimens.
AB  - CONTEXT: Search for a cost-effective, rapid and accurate test has renewed
      interest in mycobacteriophage as a tool in the diagnosis of tuberculosis (TB).
      There has been no reported data on the performance of phage assay in a high
      burden, low-resource setting like Kanpur city, India. AIMS: To assess the
      sensitivity and specificity of the FASTPlaque TB kit ability to impact the
      bacillary load in the phage assay and its performance in the sputum smear sample
      negative cases. MATERIALS AND METHODS: The study involved a cross-sectional
      blinded assessment of phage assay using the FASTPlaque TB kit on 68 suspected
      cases of pulmonary TB against sputum smear microscopy by Ziehl-Neilsen staining
      and culture by the LJ method. RESULTS: The sensitivity, specificity and positive
      and negative predictive values of the phage assay were 90.7, 96, 97.5 and 85.7%,
      respectively. The assay was negative in all the five specimens growing
      mycobacteria other than TB. The sensitivity of the phage assay tended to decrease
      with the bacillary load. Of the smear-negative cases, three were false negative,
      and all of which were detected by the phage assay. Smear microscopy (three smears
      per patient) had a sensitivity and specificity of 93 and 64%, respectively.
      CONCLUSIONS: The phage assay has the potential clinical utility as a simple means
      of rapid and accurate detection of live Mycobacterium tuberculosis bacilli;
      however, its performance has been inconsistent across various studies, which
      highlights that the assay requires a high degree of quality control demanding
      infrastructure and its performance is vulnerable to common adversities observed
      in "out of research" practice settings like storage, transport and cross
      contamination.

PMID- 19384037
TI  - Seroprevalence of hepatitis E virus immunoglobulin G and M antibodies in adults:
      a hospital-based study.
AB  - Sporadic cases of Hepatitis E virus (HEV) infection occur throughout the year in
      Pakistan. The aim of this study was to determine the prevalence of HEV
      immunoglobulin (Ig) G and IgM antibodies in 93 hepatitis B and C-negative
      patients as such patients are not routinely tested further despite having signs
      and symptoms of hepatitis. Anti-HEV IgG and IgM were detected by the enzyme
      linked immunosorbant assay technique. Among them five patients (5.4%) were
      positive for HEV IgG and IgM, with an average age of 30.95 +/- 15.35 years.
      Hepatitis E infection was independent of the sex. Liver function tests of
      hepatitis E-positive IgG and IgM patients showed increased values of serum
      glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase,
      alkaline phosphatase and bilirubin that indicate damaged hapatocytes and
      malfunctioning of the liver.

PMID- 19384038
TI  - Stacking gels: A method for maximising output for pulsed-field gel
      electrophoresis.
AB  - Pulsed field gel electrophoresis (PFGE), the gold standard of molecular typing
      methods, has a major disadvantage of an unusually long electrophoretic time. From
      the original protocol of 6 days, it was modified to 3 days and subsequently to a
      single day. We describe the procedure of stacking five to six gels one on top of
      another in order to increase and maximize the output in a shorter time without
      compromising the resolution and reproducibility. All the variables that affect
      pulsed field gels during electrophoresis were taken into consideration. We
      firstly optimized the parameters to be used and secondly determined whether
      stacking of five to six gels had any effect on the molecular separation during
      electrophoresis in comparison with a single gel run. DNA preparation,
      restriction, electrophoresis, staining and gel documentation was carried out
      based on previously published methods. Gels were analysed using BioNumerics and
      dice coefficient and unweighted pair group methods were used to generate
      dendrograms based on 1.5% tolerance values. Identical band profiles and band
      resolution-separation were seen in the PFGE patterns with single gel and multiple
      stacking gels. Cluster analysis further strengthened the fact that results from
      stacking gels were reproducible and comparable with a single gel run. This method
      of stacking gels saves time and maximizes the output at the same time. The run
      time for a single gel was about 28 hours, but with six stacked gels the run time
      was 54 hours compared with 28 x 6 = 168 hours if they were run separately as
      single gels thus saving time of 67.86%. Beside the big factor of saving time,
      stacking gels save resources (electricity, reagents, water, chemicals and working
      time) by increasing the sample throughput in a shorter time without compromising
      on quality of data. But optimization of working parameters is vital depending on
      the PFGE system used.

PMID- 19384039
TI  - Factors affecting the nasal carriage of methicillin-resistant Staphylococcus
      aureus in human immunodeficiency virus-infected patients.
AB  - Human immunodeficiency virus-infected patients attending skin outpatient
      department were studied for nasal carriage of methicillin-resistant
      Staphylococcus aureus (MRSA) and associated factors affecting nasal colonization.
      Nasal swabs were used for isolation of S. aureus. MRSA were detected by agar
      screen and agar dilution methods. Careful examination for dermatoses was carried
      out. Forty-six of the 60 (76.67%) outpatients with HIV infection were colonized
      with S. aureus in the anterior nares. Significant number of S. aureus carriers
      were in the 31-40 year age group. Methicillin resistance was found in eight
      (17.39%) isolates. Of the 46 S. aureus strains, 29 (63%) were resistant to
      erythromycin, 69.5% to co-trimoxazole and 41.3% to ciprofloxacin. Co-trimoxazole
      use was found to be a risk factor for S. aureus carriage ( P = 0.0214) but not
      for methicillin resistance. Hospital stay for more than 10 days was a risk factor
      for methicillin resistance whereas stay for more than 25 days was found to be a
      highly significant risk factor. Dermatophytosis and herpes simplex virus
      infection were other risk factors for nasal carriage of S. aureus.

PMID- 19384040
TI  - Detection of porcine rotavirus from tissue and faecal specimens.
AB  - Porcine small intestinal sub-mucosa is a cell-free collagen matrix that has
      demonstrated its ability as a scaffold material. Transplantation poses special
      hazards because grafted tissues and organs transmit pathogens efficiently,
      especially viruses. Rotavirus is thought to be confined to the intestine, causing
      acute diarrhoea. The purpose of this study was to evaluate the porcine intestinal
      tissue scaffold for Rotavirus and to study the incidence of this virus among pig
      herds. Only one isolate was successfully adapted to grow in cell line MA 104 from
      faecal samples. This isolate was further confirmed by reverse transcriptase
      polymerase chain reaction and sequence analysis.

PMID- 19384041
TI  - Leptospirosis outbreak in 2005: L.T.M.G. hospital experience.
AB  - Nine hundred and forty two serum samples from clinically suspected cases of
      leptospirosis admitted in Lokmanya Tilak Municipal General Hospital, Mumbai
      during July-September 2005 were tested by LeptoTek Dri-dot/Leptocheck. One
      hundred and sixty five positive sera by these tests were sent to I.R.R., Mumbai,
      for detection of leptospira IgM antibodies by ELISA (PanBio). Eighty seven
      positive sera were also sent to B.J. Medical College, Pune, for microscopic
      agglutination test (MAT) for serovar identification. Seropositivity with LeptoTek
      Dri-dot/Leptocheck was 34.3%. Adults and males predominated. All patients were
      febrile. The commonest presentation in adults was jaundice (81.4%), followed by
      oliguria (37.6%). In children, myalgia was commonest (75.6%), followed by
      conjunctival suffusion (54.7%). IgM ELISA positivity was 69.1% and MAT positivity
      was 29.9%. Commonest serovar detected in this geographical area was Leptospira
      icterohaemorrhagiae (42.9%), followed by L. bataviae, L. tarassovi, and L. pomona
      . Considering at least two of the above three serological tests positive, 127
      cases could be diagnosed and only 89.8% of them could be diagnosed by ELISA and
      rapid test. Therefore, along with rapid serological tests, IgM ELISA should be
      routinely done for laboratory diagnosis of leptospirosis.

PMID- 19384042
TI  - Unusual presentation of entomophthoromycosis.
AB  - Rhinoentomophthoromycosis caused by Conidiobolus sp commonly presents as a
      chronic granulomatous lesion that affects the rhinofacial subcutaneous tissue. We
      present an 18-year-old girl who presented with progressive bilateral proptosis
      and loss of vision since 2 weeks. Biopsy and fungal cultures confirmed diagnosis
      of Conidiobolus sp infection of the paranasal sinuses bilaterally with orbital
      extension and blindness. The clinical picture was complicated by the presence of
      sputum-positive cavitatory pulmonary tuberculosis, which was diagnosed at the
      same time. To our knowledge, this is the first such case to be reported from
      India. We also discuss the management of entomophthoromycosis. Despite many
      reports of success, there remains no consensus on the treatment of Conidiobolus
      infections of the nose and the paranasal sinuses with antifungal agents.

PMID- 19384043
TI  - Diagnosis of spontaneous bacterial peritonitis: Role of tween 80 and triton X in
      ascitic fluid cultures.
AB  - A patient with alcoholic cirrhosis of the liver, portal hypertension with hepatic
      encephalopathy and spontaneous bacterial peritonitis (SBP) was admitted in an
      obtunded condition. Attempts at delineating the aetiology of the SBP using
      conventional cultures as well as automated systems were not successful. The use
      of non-anionic surfactant agents such as Tween 80-incorporated blood agar and
      Triton X treatment of the specimens facilitated the growth of Klebsiella
      pneumoniae from the ascitic fluid, which otherwise would have been concluded to
      represent culture-negative neutrocytic ascites. Thus, the use of the
      aforementioned agents could be explored in elucidating the aetiology of body
      cavity infections when conventional methods fail.

PMID- 19384044
TI  - Pulmonary botryomycosis in a patient with down syndrome.
AB  - Pulmonary botryomycosis is a rare chronic, pyogranulomatous infection affecting
      the lung parenchyma. We describe here the clinical and histopathological findings
      of pulmonary botryomycosis reported for the first time in a Down syndrome female
      who required prolonged intensive care. This case has other different unique
      aspects. It is the first case to present with empyema, the second case involving
      the right lower lobe and the first case managed by decortication.

PMID- 19384045
TI  - Post-traumatic osteomyelitis due to aeromonas species.
AB  - We report a case of Aeromonas osteomyelitis due to injury in a sewage worker. He
      presented with cellulitis of the left foot. Radiographs showed evidence of
      osteomyelitis involving the head and neck of the fifth metatarsal. Aeromonas
      species was isolated from the tissue and swab from the foot. The head and neck of
      the fifth metatarsal were excised and the patient improved on 4 weeks of
      intravenous meropenem followed by 4 weeks of oral clindamycin and ciprofloxacin.

PMID- 19384046
TI  - Circulating phage type of Vibrio cholerae in Mysore.

PMID- 19384047
TI  - Seroprevalence of human immunodeficiency virus and syphilis in blood donors of
      Delhi.

PMID- 19384048
TI  - Nocardia puris endophthalmitis.

PMID- 19384049
TI  - Combination of three rapid tests: An alternative approach to confirmatory
      laboratory diagnosis of HIV infection in Bangladesh.

PMID- 19384050
TI  - Epidemiology of candida bloodstream infections in a tertiary care institute in
      India.

PMID- 19384051
TI  - Cryptosporidial oocysts in gastric aspirate of an infant.

PMID- 19384052
TI  - Immunosuppression level in HIV-positive patients with oropharyngeal candidiasis.

PMID- 19384053
TI  - Male germline stem cell division and spermatocyte growth require insulin
      signaling in Drosophila.
AB  - Spermatogenesis in Drosophila commences with cell division of germline stem cells
      (GSCs) to produce male germline cells at the tip of the testis. However,
      molecular mechanisms inducing division of male GSCs have not been reported.
      Insulin-like peptides are known to play an essential role in stimulation of
      proliferation and growth of somatic cells, and it has recently been reported that
      such peptides promote cell division in female Drosophila GSCs. However, their
      effects on male germline cells have not been characterized. We found that
      inhibition of insulin production and insulin signaling mutations resulted in
      decreased numbers of germline cells in Drosophila testes. GSC numbers were
      maintained in young mutant males, with a gradual decrease in abundance of GSCs
      with age. Furthermore, in mutants, fewer germline cysts originated from GSCs and
      a lower frequency of GSC division was seen. Insulin signaling was found to
      promote cell cycle progression of the male GSCs at the G(2)/M phase. The cell
      volume of spermatocytes increases up to 25 times before initiation of meiosis in
      Drosophila. We examined whether insulin signaling extrinsically induces the
      greatest cell growth in Drosophila diploid cells and found that spermatocyte
      growth was affected in mutants. The results indicate that in addition to its
      function in somatic cells, insulin signaling plays an essential role in cell
      proliferation and growth during male Drosophila gametogenesis and that sperm
      production is regulated by hormonal control via insulin-like peptides.

PMID- 19384054
TI  - Potencies of centrally- or peripherally-injected full-length kisspeptin or its C
      terminal decapeptide on LH release in intact male rats.
AB  - The aim of the present study was to compare the effects of full-length rat
      kisspeptin (rKp-52) with C-terminal decapeptide (Kp-10) of rat or human
      kisspeptin on LH release in intact male rats. Plasma LH profiles were determined
      by frequent blood sampling at 6-min intervals for 3 h after central or peripheral
      injection of kisspeptins. Intracerebroventricular (icv) injection of rKp-52 (0.1
      nmol) induced a gradual increase in the plasma LH level, which remained high for
      the rest of the sampling period. On the other hand, icv injection of rKp-10 did
      not increase the plasma LH level at the same dose (0.1 nmol). A 10-times higher
      dose (1 nmol) of rKp-10 and hKp-10 increased the plasma LH level, but the
      increase was lower than that of rKp-52 icv injection. Intravenous (iv) injection
      of kisspeptins also stimulated LH release at 10 or 100 nmol/kg. In rKp-52 (10
      nmol/kg)-treated animals, the plasma LH level reached a peak within 30 min and
      remained high until 60 min postinjection. The rKp-10- and hKp-10-injected animals
      showed a more rapid decline in plasma LH level after the peak found at around 30
      min after the injections at both middle (10 nmol/kg) and high (100 nmol/kg)
      doses. The present study indicates that full-length kisspeptin is more effective
      in stimulating LH release compared with Kp-10 in male rats. The difference in LH
      releasing activity may be the result of a difference in degradation of the
      peptides, but it is still worth determining whether an active domain other than
      the C-terminal decapeptide is present in full-length kisspeptin.

PMID- 19384055
TI  - Radiation protection by 6-palmitoyl ascorbic acid-2-glucoside: studies on DNA
      damage in vitro, ex vivo, in vivo and oxidative stress in vivo.
AB  - A palmitoyl derivative of ascorbic acid 2-glucoside, 6-palmitoyl ascorbic acid-2
      glucoside (PAsAG), which possess good antioxidant properties, is examined for
      radioprotection in vitro, ex vivo and in vivo models. PAsAG protected plasmid DNA
      from gamma-radiation induced damages under in vitro conditions. Presence of 1.6
      mM PAsAG inhibited the disappearance of ccc (covalently closed circular) form of
      plasmid pBR322 with a dose modifying factor of 1.5. Comet assay studies on mouse
      spleen cells exposed to 6 Gy gamma-radiation (ex vivo) in presence and absence of
      PAsAG revealed that cellular DNA was effectively protected by this compound from
      radiation induced damages. Oral administration of 80 mg/kg body weight of PAsAG
      to mice 1 hour prior to 6 Gy whole body gamma-radiation exposure, efficiently
      protected cellular DNA in tissues such as spleen, bone marrow and blood, from
      radiation induced damages as indicated by alkaline comet assay. Oxidative stress
      in tissues such as liver and brain of mice, following whole body exposure to
      various doses of gamma-radiation (2-8 Gy), monitored as levels of GSH and
      peroxidation of lipids, were found considerably reduced when PAsAG was orally
      administered (80 mg/kg body weight) to the mice one hour prior to the radiation
      exposure. PAsAG administration improved the per cent survival of mice following
      exposure to 10 Gy whole body gamma-radiation. Thus PAsAG could act as a
      radioprotector under in vitro, ex vivo and in vivo conditions of ionizing
      radiation exposure.

PMID- 19384056
TI  - The determination of absolute intensity of 234mPa's 1001 keV gamma emission using
      Monte Carlo simulation.
AB  - The 1001 keV gamma line of (234m)Pa became important in gamma spectrometric
      measurements of samples with (238)U content with the advent of development of
      HpGe detectors of great dimension and high efficiency. In this study the emission
      probability of the 1001 keV (Y(gamma)) peak of (234m)Pa, was determined by gamma
      ray spectrometric measurements performed on glass with Uranium content using
      Monte Carlo simulation code for efficiency calibration. This method of
      calculation was not applied for the values quoted in literature so far, at least
      to our knowledge. The measurements gave an average of 0.836 +/- 0.022%, a value
      that is in very good agreement to some of the recent results previously
      presented.

PMID- 19384057
TI  - An essential interaction between T-box proteins and histone-modifying enzymes.
AB  - Cellular differentiation requires precisely coordinated events to induce
      developmentally appropriate gene expression profiles. Lineage-defining
      transcription factors are responsible for establishing cell-type specific gene
      expression patterns during development. Recently, we reported a novel mechanism
      by which the T-box transcription factor T-bet interacts with JMJD3, an H3K27
      demethylase, and Set7/9, an H3K4-methyltransferase (Genes Dev. 2008. 22: 2980
      2993). Importantly, separable contact points in the T-box DNA binding domain
      mediate these interactions. Due to the highly conserved nature of the contact
      residues, these represent common interactions for the T-box family. Therefore,
      studies examining the molecular mechanisms that account for the ability of T-bet
      to regulate Ifng and Cxcr3, prototypic CD4+ Th1 genes, have provided novel
      insight into essential regulatory events that occur at diverse developmental
      transitions. In this article, we discuss the implications for these findings as
      well as explore the role epigenetic mechanisms may play in the development of
      human genetic diseases that are caused by T-box mutations, including congenital
      heart defects, cleft palate, pituitary deficiencies, and Ulnar-mammary syndrome.

PMID- 19384058
TI  - Determining the conservation of DNA methylation in Arabidopsis.
AB  - A high-resolution map of DNA methylation in Arabidopsis has recently been
      generated using high-throughput sequencing of bisulfite-converted DNA. This
      detailed profile measures the methylation state of most of the cytosines in the
      Arabidopsis genome, and allows us for the first time to address questions
      regarding the conservation of methylation across duplicated regions of the
      genome. To address these questions we measured the degree to which methylation is
      conserved in both duplicated genes and duplicated non-coding regions of the
      genome. Methylation is controlled by different mechanisms and methyltransferases
      depending on the genomic location. Methylation in genes occurs primarily at CG
      sites and is controlled by the maintenance methyltransferase MET1. In contrast,
      an RNAi mediated methylation pathway that leads to de novo methylation of
      asymmetric CHH sites along with CG and CHG sites by the methyltransferase DRM2,
      drives methylation at tandem and inverted repeats. We find that the cytosine
      methylation profile is strongly preserved between duplicated genes and repeat
      regions. The highest level of conservation can be found at CG sites in genes and
      CHH sites in repeat regions. By constructing substitution matrices between
      aligned genes we see that methylated cytosines often pair with thymines, which
      may be explained by the spontaneous deamination of methyl-cytosine to thymine.
      Despite this observation, we find that methylated cytosines are less often paired
      with other nucleotides than non-methylated cytosines within gene bodies
      indicating that they may play an important functional role.

PMID- 19384059
TI  - Intravascular eosinophilic deposits-when common knowledge is insufficient to
      render a diagnosis.
AB  - In the course of daily sign-out, the diagnoses within a histopathologist's
      armamentarium are limited by the scope of the histopathologist's knowledge, that
      is, one cannot diagnose what one does not know. The subject of homogeneous
      intravascular eosinophilic deposits is used to illustrate this point. A
      histopathologist unaware that a tick bite reaction can induce intravascular
      eosinophilic deposits may misdiagnose the specimen as representing a
      manifestation of cryoglobulinemia. Furthermore, conventional teaching imparts
      that monoclonal cryoglobulinemia shows intravascular eosinophilic deposits
      (cryoprecipitates) histopathologically, whereas mixed cryoglobulinemia is
      histopathologically manifested as leukocytoclastic vasculitis. Although it is not
      well known, this is not always the case because mixed cryoglobulinemia may
      histopathologically present itself as intravascular eosinophilic deposits without
      leukocytoclastic vasculitis. In addition, it is not common knowledge that
      intravascular cryoprecipitates, when present, may be associated with an increased
      number of blood vessels. Examples of these phenomena are presented in conjunction
      with a discussion of relevant issues/lessons learned from such cases.

PMID- 19384060
TI  - The utility of the DNA microarray scanner to simplify the immunofluorescence
      evaluation of autoimmune bullous diseases.
AB  - A DNA microarray scanner was used as a digital fluorescence microscope to
      simplify the diagnosis of autoimmune bullous diseases. Frozen sections of skin
      biopsies were taken from 3 patients with bullous pemphigoid and 1 patient each
      with lichen planus pemphigoides, linear immunoglobulin (Ig) A disease, and
      dermatitis herpetiformis. After incubation with cyanine-labeled antibodies, the
      tissues were scanned at 5-mum resolution using an instrument originally designed
      to study gene expression. The microarray scanner's large field of view, unlike
      that of fluorescence microscopy, allowed a view of the entire specimen,
      considerably easing the orientation of tissue. All images were diagnostic and
      included a linear pattern along the basement membrane zone (BMZ) using anti-IgG
      and anti-C3 in all cases of bullous pemphigoid, a linear pattern of IgG along the
      BMZ in lichen planus pemphigoides, and a linear pattern of IgA along the BMZ in
      linear IgA dermatosis. IgA deposition along dermal papillary tips was seen in
      dermatitis herpetiformis, but a granular pattern was indiscernible at the 5-mum
      resolution. The advantages of the microarray scanner over standard fluorescence
      microscopy include speed, technical ease, large field of view, potential for
      visualizing multiple antibodies simultaneously in a tissue, and convenience of
      digital image archiving.

PMID- 19384061
TI  - Pigmented Paget disease--a diagnostic pitfall mimicking melanoma.
AB  - Pigmented mammary and extramammary Paget disease are rare entities in both males
      and females that mimic melanoma both clinically and histologically. Furthermore,
      Paget disease can be associated with increased number of benign melanocytes, thus
      resulting in additional diagnostic difficulty, especially when only hematoxylin
      and eosin-stained sections are examined and a limited immunohistochemical study
      is performed. Using standard hematoxylin and eosin-stained sections and routine
      immunohistochemical studies, we describe and characterize 7 cases of pigmented
      extramammary and mammary Paget disease. In all cases, malignant epithelial cells
      showed intracytoplasmic pigment, along with an immunohistochemical epithelial
      phenotype. In 2 of the cases, immunohistochemistry revealed numerous dendritic
      processes positive for melanocytic markers, thus resulting in an initial
      diagnosis of melanoma. Careful analysis confirmed that the immunolabeling
      corresponded to cytoplasmic labeling of melanocyte dendrites surrounding tumor
      cells. The correct diagnosis of pigmented Paget disease can be reached after
      close histologic examination and detailed evaluation of immunohistochemical
      studies. The latter are especially important in some extraordinary cases in which
      there may be an associated intraepithelial melanocytic hyperplasia.

PMID- 19384062
TI  - Cutaneous nontuberculous mycobacterial infection: a clinicopathological study of
      7 cases.
AB  - Nontuberculous mycobacteria (NTM) are human opportunistic pathogens with an
      environmental source of infection. The reports of cutaneous NTM infections has
      increased, and NTM have been regarded as important pathogens in recent years.
      This study aimed to identify characteristic clinical and histological features of
      cutaneous NTM infections. We evaluated the medical records and histopathologic
      slides of 7 cases of NTM infections that were confirmed by polymerase chain
      reaction between 2003 and 2007. The results showed that cutaneous NTM infections
      occurred in various aged people independent of their immune states and were
      associated with fish-related jobs or intramuscular medicinal injection. The main
      clinical feature was a painful erythematous nodule. Histopathologically, the most
      common findings were diffuse infiltration of mixed inflammatory cells and small
      vessel proliferation in the dermis (100%). Epidermal proliferation (71%) and
      dermal granuloma (71%) were also very common. Suppurative granuloma was found in
      43% of the cases, and eosinophil infiltration was uncommon (14%). The lesions
      disappeared after a mean of 7 months (range, 1.5-12 months) with treatment by
      oral clarithromycin alone or in combination with other antimycobacterial agents.
      These clinical and histopathological data should assist clinicians in the
      diagnosis of NTM.

PMID- 19384063
TI  - Histopathology and X-ray microanalysis of foreign material on facial keratoses.
AB  - Opaque exogenous material was frequently observed on the surface of keratoses
      during routine sign out by one of us (H.K.). To investigate this material
      further, 300 consecutive seborrheic keratoses were reviewed: 100 cases from the
      face of women, 100 cases from the face of men, and 100 cases from the trunk of
      men and women. All cases were evaluated by light microscopy for the presence and
      quantity of exogenous material, and 14 cases were studied by x-ray microanalysis
      to assess its composition. The material was present on 54% of facial keratoses
      from predominantly older women (mean age 67 years), 5% of facial keratoses from
      men, and 9% of truncal keratoses from men and women. The x-ray microanalysis
      showed the presence of a variety of elements, including titanium (13 cases),
      silicon (12 cases), iron (9 cases), aluminum (8 cases), magnesium (8 cases), zinc
      (4 cases), barium (2 cases), and bismuth (2 cases). We believe that the exogenous
      material represents cosmetic products such as colored facial cosmetics,
      sunscreens, and moisturizers. Further, because the exogenous material was found
      predominantly on facial keratoses of older women, the presence of this material
      in a specimen may serve as a clue to the patient's gender, age, and biopsy site.

PMID- 19384064
TI  - Cutaneous hidradenocarcinoma: a clinicopathological, immunohistochemical, and
      molecular biologic study of 14 cases, including Her2/neu gene
      expression/amplification, TP53 gene mutation analysis, and t(11;19)
      translocation.
AB  - We present a series of 14 cases of cutaneous hidradenocarcinomas. The patients
      included 6 women and 8 men ranging in age at diagnosis from 34 to 93 years. All
      but 1 patient presented with a solitary nodule. There was no predilection site.
      One patient presented with multiple lesions representing metastatic nodules. Of
      12 patients with available follow-up, 2 died of disease, whereas the remaining 10
      patients were alive but 3 of them experienced a local recurrence in the course of
      the disease. Grossly, the tumors ranged in size from 1.2 to 6 cm.
      Microscopically, of the 14 primary tumors, 9 showed low-grade cytomorphology,
      whereas the remaining 5 neoplasms were high-grade lesions. The residuum of a
      hidradenoma was present in 5 of the 14 primaries. The mitotic rate was highly
      variable, ranging from 2 to 64 mitoses per 10 high-power field. The cellular
      composition of the tumors varied slightly, with clear cells, epidermoid cells,
      and transitional forms being present in each case. In 1 case, there was
      metaplastic transformation into sarcomatoid carcinoma. Glandular differentiation
      varied from case to case and appeared most commonly as simple round glands or as
      cells with intracytoplasmic lumens. Necrosis en masse was detected in 8
      specimens. One specimen represented a reexcision and was unusual as it showed a
      well-demarcated intradermal proliferation of relatively bland clear cells
      accompanied by an overlying intraepidermal growth of clear cells resembling
      hidradenoacanthoma simplex. Despite the bland appearance, the tumor metastasized
      to a lymph node. Immunohistochemically, 5 of the 8 specimens studied for Her2/neu
      expression were negative, whereas 3 specimens from 2 cases yielded score +2, but
      all the 3 specimens with score 2+ subsequently proved negative for Her2/neu gene
      amplification by fluorescence in situ hybridization. Of 10 primaries studied, 4
      tumors showed positive p53 immunoreaction in more than 25% of the cells
      comprising the malignant portion of the lesions, in 2 cases, a minority of the
      neoplastic cells (10%-20%) demonstrated nuclear staining, whereas the remaining 4
      cases were negative. Of 9 specimens of hidradenocarcinoma studied for TP53
      mutations, 2 harbored mutations, whereas the remaining 7 specimens showed the
      wild-type sequence. Of 11 specimens studied for translocation t(11;19), 2 cases
      harbored the translocation. It is concluded that cutaneous hidradenocarcinomas
      show some microscopic heterogeneity and comprise both low- and high-grade lesions
      that cytologically are similar to their benign counterpart, the hidradenoma.
      Within the spectrum of low-grade lesions, there seem to exist tumors almost
      indistinguishable from hidradenomas but still being capable of regional or
      distant metastasis. Similar to hidradenomas, hidradenocarcinomas show a t(11;19)
      translocation, but it is a significantly rarer event. Even rarer is the
      amplification of the Her2/neu gene. Of note is the relatively low frequency of
      TP53 mutations despite a high rate of p53 protein expression at the
      immunohistochemical level.

PMID- 19384065
TI  - Mutations in exon 3 of the CTNNB1 gene (beta-catenin gene) in cutaneous adnexal
      tumors.
AB  - Previous studies suggested that mutant beta-catenin gene cells in cutaneous
      adnexal tumors with matrical differentiation contribute to their tumorigenesis.
      Except for pilomatricoma and pilomatrical carcinoma, only a handful of other
      cutaneous adnexal tumor types have been studied. DNA was extracted from 86
      lesions including 17 proliferating tricholemmal and trichilemmal tumors, 15
      trichoblastomas, 7 trichoadenomas, 4 pilomatricomas, 1 pilomatrical carcinoma, 4
      basal cell carcinomas (BCCs) with shadow cells, 2 trichofolliculomas, 3 BCCs with
      sebaceous differentiation, 9 sebaceous adenomas, 6 sebaceomas, 14 sebaceous
      carcinomas (both ocular and extraocular forms), 2 gigantic horns, and 2 apocrine
      mixed tumors with shadow cells and subjected to polymerase chain reaction with
      newly designed primers encompassing glycogen synthase kinase-3beta
      phosphorylation sites of the CTNNB1 gene. Also, 3 craniopharyngiomas were
      studied. Sequenced polymerase chain reaction products for possible beta-catenin
      gene mutations showed a total of 8 alterations. These included 5 different point
      mutations, 3 of them identified in 2 different tumors: S23N (cribriform
      trichoblastoma), D32Y (pilomatricoma and craniopharyngioma), G34R (pilomatrical
      carcinoma and craniopharyngioma), S37F (2 BCCs with shadow cell differentiation),
      and G34V (craniopharyngioma). This study broadens the list of cutaneous adnexal
      tumors harboring CTNNB1 mutations and extends the listing of the mutations
      occurring in these neoplasms.

PMID- 19384066
TI  - Clinicopathological features of eyelid skin tumors. A retrospective study of 5504
      cases and review of literature.
AB  - Eyelid tumors are the most common neoplasm in daily ophthalmology practice and
      encompass a wide variety of benign and malignant tumors. In this retrospective
      study, we report the clinical and histological features of 5504 eyelid skin
      tumors diagnosed at the Laboratory of Ophthalmopathology of the Hopital
      Ophtalmique Jules Gonin, Lausanne, Switzerland, between January 1989 and December
      2007. Benign tumors largely predominated over malignant ones, representing 84% of
      cases in this series, and the 5 most frequent subtypes were squamous cell
      papilloma (26%), seborrheic keratosis (21%), melanocytic nevus (20%),
      hidrocystoma (8%), and xanthoma/xanthelasma (6%). Basal cell carcinoma was the
      most frequent malignant tumor (86%), followed by squamous cell carcinoma (7%) and
      sebaceous carcinoma (3%). For several tumor subtypes, there was a poor
      correlation between clinical and histological diagnosis, stressing the numerous
      pitfalls in the diagnosis of eyelid tumors. We further discuss our results with
      reference to previously published series.

PMID- 19384067
TI  - Annular lichenoid dermatitis of youth ... and beyond: a series of 6 cases.
AB  - Annular lichenoid dermatitis of youth (ALDY) is a clinico-pathologic entity
      described in children and young patients, clinically reminiscent of morphea,
      annular erythema, vitiligo or mycosis fungoides. We report on six patients
      presenting single or multiple lesions, distributed particularly on the flanks and
      abdomen, with clinical and histologic features consistent with ALDY. Two patients
      were young girls and four were adults males. Three patients received topical
      therapy and four showed complete resolution of the lesions after a 24-65 months
      follow-up. Analogously to the cases reported so far, immunohistochemistry showed
      a T cell infiltrate with a predominance of CD8+ lymphocytes, while T cell
      receptor rearrangement was absent in all cases. It seems appropriate to include
      annular lichenoid dermatitis of youth among the dermatoses with a lichenoid
      pattern. For the first time, we found that it can affect also adult patients,
      therefore we propose to rename the disease annular lichenoid dermatitis. The
      differential diagnosis with mycosis fungoides, especially in adult patients, is
      particularly crucial for their proper management and treatment.

PMID- 19384068
TI  - Histoid leprosy: histopathological connotations' relevance in contemporary
      context.
AB  - A reappraisal of histoid leprosy in the contemporary postglobal leprosy
      elimination era, a fallout of the World Health Organization leprosy elimination
      program, is succinctly outlined. The cardinal clinical expression, differential
      clinical diagnosis, the cytodiagnosis, and diagnostic salient histopathological
      features are highlighted.

PMID- 19384069
TI  - Crystal-deficient alveolar soft-part sarcoma with cutaneous involvement: a case
      report.
AB  - Alveolar soft-part sarcoma (ASPS) is a rare distinctive sarcoma, in most cases
      involving deep soft tissues of the extremities. It is associated with a specific
      unbalanced translocation, der(17)t(X;17)(p11;q25) that results in the formation
      of an ASPL-TFE3 fusion gene. Microscopically, it is typified by an alveolar
      growth of large cells containing typical periodic acid-Schiff-positive rod-shaped
      crystals, often serving as a diagnostic clue. Other distinctive features include
      nuclear immunoreactivity for transcription factor 3 (TFE3) protein and a typical
      ultrastructural finding of large crystals with a rectangular or rhomboid shape.
      The authors present an unusual case of ASPS with cutaneous involvement, which did
      not exhibit typical large crystals; there were striking round granules. Molecular
      genetic study revealed fusion transcript ASPL-TFE3, type 2. To the best of our
      knowledge, cutaneous involvement of a crystal-deficient ASPS has not been
      reported.

PMID- 19384070
TI  - Cutaneous adnexal tumor with an unusual presentation--discussion of a potential
      diagnostic pitfall.
AB  - The clinical presentation of skin adnexal tumors is nonspecific, and
      histologically; the differential diagnosis between primary cutaneous adnexal
      malignant carcinomas and metastatic tumors with a visceral origin can be
      challenging. We report a patient with history of invasive ductal carcinoma of the
      breast who presented with a 1-cm erythematous palpable lesion on her right calf.
      The biopsy showed an intradermal proliferation of malignant epithelioid cells
      with ductal differentiation, histologically compatible with metastatic breast
      carcinoma. However, the tumor cells labeled strongly and diffusely not only for
      pancytokeratin and cytokeratin (CK7) but also with p63 and CK5/6;
      carcinoembryonic antigen highlighted the ductal structures. No labeling was seen
      for mammoglobin, estrogen/progesterone, Her2-neu, S-100 protein, CK20, thyroid
      transcription factor-1 (TTF-1), and CDX-2. Based on the p63 and CK5/6 positivity,
      the differential diagnosis also included the possibility of a primary adnexal
      neoplasm and a complete excision was advised. The reexcision specimen revealed
      residual infiltrating dermal tumor and an overlying intraepithelial component
      with marked cytologic atypia and focal duct formation, diagnostic of a primary
      cutaneous adnexal tumor with ductal differentiation (porocarcinoma).
      Immunohistochemical studies (like p63 and CK5/6) can help to differentiate a
      primary cutaneous neoplasm from a metastatic lesion. This discrimination is of a
      paramount importance because a diagnostic error can result in profound
      implications for patient's assumed prognosis and subsequently applied therapy.

PMID- 19384071
TI  - Osteoclast-like giant cell reaction associated with cutaneous squamous cell
      carcinoma: a report of 2 cases and review of the literature.
AB  - The observation of osteoclast-like giant cells (O-LGCs) in intimate association
      with visceral malignancies is an uncommon phenomenon that has been recognized for
      over 40 years. Recently, the same observation has been made in relation to
      cutaneous malignancies. In an article published in 2005, O-LGCs were documented
      in association with 3 melanomas, and since then, there have been 3 separate case
      reports recording the presence of these cells in cutaneous carcinomas. In the
      context of both visceral and cutaneous malignancies, the exact nature of the O
      LGCs has been a source of controversy, with respect to whether they represent
      modified tumor cells or an unusual host response to the neoplasm. We report here
      2 additional cases of cutaneous squamous cell carcinoma associated with O-LGCs.
      The morphological pattern of the giant cell proliferation differed between these
      cases, taking the form of (1) a giant cell tumor-like nodule apposed to the
      carcinoma in one and (2) scattered O-LGCs interspersed with tumor cells in the
      other. Based on scrutiny of routine sections and the contrasting
      immunohistochemical profiles of the O-LGCs versus the carcinomas, showing CD68
      positivity on one hand and high-molecular weight keratin and p63 positivity on
      the other, we concluded that in both instances, the O-LGC proliferation was a
      reactive phenomenon. This theory is supported by most publications on the
      subject. Clinical and histopathological details of the new cases are outlined and
      integrated with those in the literature.

PMID- 19384072
TI  - Concomitant lucio phenomenon and erythema nodosum in a leprosy patient: clues for
      their distinct pathogeneses.
AB  - Lepromatous leprosy patients may develop necrotic lesions, usually in the context
      of Lucio phenomenon (LP) or severe erythema nodosum (EN). The clinical and
      histopathological characteristics of the necrotic manifestations of both entities
      may eventually be confounded. We describe a patient with lepromatous leprosy who
      developed, since the 4th month of her first pregnancy, recurrent necrotic lesions
      in lower limbs, which, at the postpartum, worsened and led to partial destruction
      of ears and nose. In addition, she referred painful nodes on upper limbs since 1
      year before pregnancy and intermittent swelling and tenderness of the ankles,
      which together with a right tibial and ulnar neuritis led to the diagnosis of,
      erythema nodosum leprosum (ENL). The histopathology of a biopsy of the upper limb
      (ENL) revealed a dermal-hypodermal inflammation with vasculitis and vascular
      lumen narrowing, whereas biopsy of the lower limb (LP) revealed small vessels
      with fibrin thrombi on the superficial layer of the dermis without inflammatory
      infiltrate and no evidence of vasculitis. Thus, besides having several different
      clinical features, LP and ENL result from different pathogenetic mechanisms. The
      histopathological and clinical features distinguishing both entities are
      proposed. This distinction is important because decrease in bacillary load
      through multidrug therapy is the main target in LP, whereas in ENL, concomitant
      reduction of the reaction by means of thalidomide or high-dose steroids is
      recommended.

PMID- 19384073
TI  - Livedoid vasculopathy with underlying subcutaneous necrotizing venulitis in an
      asymptomatic hepatitis B virus carrier: is livedoid vasculopathy a true
      nonvasculitic disorder?
AB  - Livedoid vasculopathy has been accepted as a nonvasculitic disorder, but
      authentic vasculitis in the underlying subcutis can occur in cases of collagen
      disease and polyarteritis nodosa. We report a case of livedoid vasculopathy with
      underlying subcutaneous necrotizing venulitis in a 42-year-old carrier of
      hepatitis B virus. The patient also had a 15-year history of ankylosing
      spondylitis that was currently in remission. Skin lesions revealed superficial
      ulceration, purpura, atrophie blanche, and reticulate erythema on the lower
      extremities, and a skin biopsy showed a minimal dermal perivascular lymphocytic
      infiltrate with marked fibrin thrombi and fibrin deposits along luminal vessel
      walls, consistent with features of livedoid vasculopathy. However, necrotizing
      venulitis characterized by a predominant lymphocytic infiltrate in and around the
      vessel wall with marked fibrinoid vessel wall necrosis was found in the
      underlying subcutaneous tissue. A direct immunofluorescence study detected
      immunoglobulin M and C3 deposits in the papillary dermis. The patient responded
      well to oral aspirin and a prostaglandin analogue and was well controlled with a
      compression bandage. Vasculitic lesions in the underlying subcutis may have been
      overlooked in cases in which livedoid vasculopathy has been considered as a
      nonvasculitic disorder because our case demonstrates that livedoid vasculopathy
      can be accompanied by subcutaneous vasculitis.

PMID- 19384074
TI  - Cutaneous and subcutaneous metastases of gastrointestinal stromal tumors: a
      series of 5 cases with molecular analysis.
AB  - Gastrointestinal stromal tumors (GISTs) rarely metastasize to the skin. We
      describe 5 patients with GIST with subcutaneous and cutaneous metastases. The
      mean age at metastasis was 54 years (range 30-68 years) with a male predominance
      (4:1). Primary tumors occurred in the stomach (n = 3), small bowel (n = 1), and
      abdomen, not otherwise specified (n = 1). The average time from primary tumor
      resection to the resection of skin metastases was 59 months (range 11-155
      months). The metastases occurred in the scalp (n = 2), cheek (n = 1), and abdomen
      (n = 2) with 3 patients presenting with solitary nodules and 2 patients with
      multiple nodules. The average size was 2 cm (range 0.6-4 cm). Histologically, 2
      cases were spindled and 3 cases demonstrated mixed epithelioid and spindle cell
      morphology. All were confirmed to have CD117 reactivity. KIT genotyping was
      performed in 4 of 5 cases. Two cases harbored a mutation in exon 11, and the
      remaining 2 cases were wild type in exons 9, 11, 13, and 17. All 5 patients had
      multiple concurrent or subsequent abdominal and/or hepatic metastases. In 4
      patients with an average follow-up of 32 months (range 6-75 months), after the
      resection of the metastases, 2 were alive with disease and 2 died of disease.
      Cutaneous metastases seem to be a late complication of GIST, but their presence
      does not necessarily herald a rapid demise of the patient.

PMID- 19384075
TI  - Epidermotropic chondroid metastasis of melanoma: report of a case of metastatic
      melanoma with previously unreported morphological features.
AB  - A potential diagnostic pitfall in the management of patients with melanoma is the
      inability to recognize metastatic melanoma, especially if it shows unusual
      features. We describe a case of multiple epidermotropic metastatic melanoma,
      which finally recurred with an extensive chondroid differentiation. To our
      knowledge, this is the first description of a case of epidermotropic chondroid
      metastatic melanoma.

PMID- 19384076
TI  - Melan-a-positive "pseudomelanocytic nests": a pitfall in the histopathologic and
      immunohistochemical diagnosis of pigmented lesions on sun-damaged skin.
AB  - We encountered recently 3 cases with a histopathologic diagnosis of melanoma in
      situ on sun-damaged skin (male = 2, female = 1; median age: 59 years; range: 52
      60 years). The diagnosis was based mainly on the finding of actinic elastosis in
      the dermis and increased number of melanocytes in the epidermis and was confirmed
      by strong positivity for Melan-A in single cells and in small nests
      ("pseudomelanocytic nests"), located at the dermoepidermal junction. Indeed,
      examination of slides stained with hematoxylin and eosin revealed the presence of
      marked hyperpigmentation and small nests of partially pigmented cells at the
      dermoepidermal junction, positive for Melan-A. The histologic and especially the
      immunohistochemical features were indistinguishable from those of melanoma in
      situ on chronic sun-damaged skin. In addition, a variably dense lichenoid
      inflammation was present. Clinicopathologic correlation, however, showed, in all
      patients, the presence of a lichenoid dermatitis (phototoxic reaction, 1 case;
      lichen planus pigmentosus, 1 case; and pigmented lichenoid keratosis, 1 case).
      Our cases clearly show the histopathologic pitfalls represented by lichenoid
      reactions on chronic sun-damaged skin. Immunohistochemical investigations,
      especially if performed with Melan-A alone, may lead to confusing and potentially
      disastrous results. The unexpected staining pattern of Melan-A in cases like ours
      raises concern about the utility of this antibody in the setting of a lichenoid
      tissue reaction on chronic sun-damaged skin. It should be underlined that
      pigmented lesions represent a paradigmatic example of how immunohistochemical
      results should be interpreted carefully and always in conjunction with histologic
      and clinical features.

PMID- 19384077
TI  - Rhabdomyomatous mesenchymal hamartoma mimicking basal cell carcinoma.

PMID- 19384078
TI  - Seborrheic inclusion cysts: a study of human papillomavirus infection by
      polymerase chain reaction.

PMID- 19384079
TI  - Rab3B immunoexpression in human pituitary adenomas.
AB  - Rab3B, a member of the Rab family is a low molecular weight GTP-binding protein
      that has been implicated in the regulation of exocytosis. To shed light on its
      presence in the normal human pituitary and in adenomas, a detailed
      immunohistochemical study of 130 surgically removed human pituitary adenomas was
      undertaken, including 23 somatotroph, 32 lactotroph, 19 functional corticotroph,
      10 silent subtype 1 and 8 silent subtype 2 corticotroph adenomas, 12 gonadotroph
      hormone producing, 10 thyrotroph, 7 silent subtype 3 adenomas, and 9 null cell
      adenomas, 5 of the latter being of oncocytic type. Among the 32 prolactin
      lactotroph adenomas, 10 had been treated preoperatively with bromocriptine, a
      dopamine agonist. Among the 23 somatotroph adenomas, 10 were pretreated with
      octreotide, a long acting somatostatin analog. In addition, 10 nontumorous
      adenohypophyses were also examined. As used by the World Health Organization, the
      tumors were classified on the basis of their histologic, immunohistochemical, and
      ultrastructural characteristics. The results showed Rab3B immunopositivity to be
      strongest in corticotroph adenomas followed by thyrotroph, lactotroph,
      gonadotroph, null cell, and somatotroph adenomas. No difference was noted between
      endocrinologically active and silent corticotroph adenomas. Bromocriptine therapy
      was associated with decreased Rab3B immunoexpression, whereas pretreatment with
      octreotide induced no significant reduction. Immunopositivity was cytoplasmic and
      was evenly distributed. No staining was noted in normal adenohypophyses. Our
      results add new information to the view that Rab3B is involved in the regulation
      of pituitary hormone secretion.

PMID- 19384080
TI  - Molecular markers in thyroid fine-needle aspiration biopsy: a prospective study.
AB  - BACKGROUND: Fine-needle aspiration biopsy (FNAB) is the most accurate study in
      the preoperative evaluation of patients with thyroid nodules. However, one of its
      limitations is the indeterminate or suspicious sample which accounts for 15% to
      25% of the cases; both follicular and Hurthle cell neoplasms are included in this
      category. OBJECTIVE: To assess the accuracy of the molecular markers HBME-1 and
      galectin-3 in suspicious or indeterminate FNABs comparing the results with the
      histologic diagnosis of the thyroidectomy specimen. MATERIALS AND METHODS: A
      prospective study was carried out at 2 Health Centers in Santiago, Chile. From
      July 2003 to March 2008, 418 FNABs with indeterminate or suspicious diagnosis
      were immunostained with HBME-1 and galectin-3. Immunohistochemistry was performed
      on a clot obtained by FNAB, which was formalin-fixed and paraffin-embedded. The
      results were matched with the definitive histologic diagnosis of the
      thyroidectomy specimen. RESULTS: Of 418 patients submitted to FNAB with
      immunohistochemistry, 138 patients underwent surgery. The sensitivity,
      specificity, positive predictive value, and negative predictive value were
      78.67%, 84.13%, 85.51%, and 76.81%, respectively, for HBME-1 and 82.67%, 80.95%,
      83.78%, and 79.69%, respectively, for galectin-3. Whereas the results for both
      markers combined were 94.74%, 75.81%, 82.76%, and 92.16%. CONCLUSIONS: With the
      combined use of HBME-1 and galectin-3 in indeterminate FNABs, a 10% increase in
      sensitivity is achieved. These markers show excellent sensitivity and specificity
      and may improve patient's selection for surgery.

PMID- 19384081
TI  - Epithelioid sarcoma of the vulva in a 17-year-old pregnant woman.
AB  - Epithelioid sarcoma of the vulva is an extremely rare neoplasm with aggressive
      behavior and poor outcome. Herein, we report a case of vulvar epithelioid sarcoma
      presenting in a 17-year-old very early in her pregnancy. The patient presented
      with an asymptomatic nodule of the right labia majora of 1-year duration.
      Computerized tomographic scans showed enlarged inguinal lymph nodes and numerous
      lung nodules. Positron emission tomography was performed and revealed no
      suspicious lesions for metastatic disease. The patient underwent local excision
      of her vulvar lesion. On the basis of morphology and extensive
      immunohistochemistry, the lesion was classified as epithelioid sarcoma. The
      patient was referred to radiation therapy and upon evaluation, she was found to
      be in her sixth week of gestation. The patient continued with her pregnancy and
      underwent a lymph node dissection, which was positive. We review the literature
      of only the well-documented cases extensively studied by immunohistochemical
      analysis. We summarize the clinical presentation, clinical impression, treatment
      modalities, and outcomes of these cases. On account of the rarity of this disease
      in the vulva, there is no clear consensus on treatment modalities, but it seems
      that early aggressive surgical resection is the treatment of choice, with the
      role of adjuvant therapy to be determined.

PMID- 19384082
TI  - Targeting heme oxygenase: therapeutic implications for diseases of the
      cardiovascular system.
AB  - Heme oxygenase (HO) is important in attenuating the overall production of
      reactive oxygen species through its ability to degrade heme and to produce carbon
      monoxide, biliverdin/bilirubin, and release of free iron. Excess free heme
      catalyzes the formation of reactive oxygen species, which leads to endothelial
      cell (EC) dysfunction as seen in numerous pathologic vascular conditions
      including systemic hypertension and diabetes, as well as in ischemia/reperfusion
      injury.The up-regulation of HO-1 can be achieved through the use of
      pharmaceutical agents such as metalloporphyrins and statins. In addition, atrial
      natriuretic peptide and nitric oxide donors are important modulators of the heme
      HO system, either through induction of HO-1 or the increased biologic activity of
      its products. Gene therapy and gene transfer, including site- and organ-specific
      targeted gene transfer have become powerful tools for studying the potential role
      of the 2 isoforms of HO, HO-1/HO-2, in the treatment of cardiovascular disease,
      as well as diabetes. HO-1 induction by pharmacological agents or the in vitro
      gene transfer of human HO-1 into ECs increases cell cycle progression and
      attenuates angiotensin II, tumor necrosis factor-alpha, and heme-mediated DNA
      damage; administration in vivo corrects blood pressure elevation after
      angiotensin II exposure. Delivery of human HO-1 to hyperglycemic rats
      significantly lowers superoxide levels and prevents EC damage and sloughing of
      vascular EC into the circulation. In addition, administration of human HO-1 to
      rats in advance of ischemia/reperfusion injury considerably reduces tissue
      damage.The ability to up-regulate HO-1 either through pharmacological means or
      through the use of gene therapy may offer therapeutic strategies for the
      prevention of cardiovascular disease in the future. This review discusses the
      implications of HO-1 delivery during the early stages of cardiovascular system
      injury or in early vascular pathology, and suggests that pharmacological agents
      that regulate HO activity or HO-1 gene delivery itself may become powerful tools
      for preventing the onset or progression of various cardiovascular diseases.

PMID- 19384083
TI  - Comparison of endovascular versus open repair of abdominal aortic aneurysms: a
      review.
AB  - The purpose of this review is to highlight the indications, complications, and
      outcomes observed with endovascular or open repair for abdominal aortic
      aneurysms. We selected literature published during 2005 to 2008, encompassing a
      research period from 1987 to 2005 which compared these 2 techniques and followed
      various outcomes of morbidity and mortality.

PMID- 19384084
TI  - Therapeutic angiogenesis in the management of critical limb ischemia: current
      concepts and review.
AB  - Critical limb ischemia (CLI) represents the most severe form of peripheral
      arterial disease. Manifestations of CLI include rest pain, ischemic ulcers,
      and/or gangrene. The presence of CLI frequently leads to amputation, and
      furthermore, patients with CLI are at an increased risk of cardiovascular events
      including death. Treatment options for CLI when revascularization is not possible
      are extremely limited. Therapeutic angiogenesis is a promising new tool in the
      management of CLI. There is a growing body of evidence demonstrating the safety
      and efficacy of therapeutic angiogenesis with gene and cell therapy. Many factors
      must be considered in formulating clinically efficacious gene and/or cell
      therapies. The dosing regimen, route of delivery, and choice of growth factor or
      cell population must be decided. Although the optimal regimen of therapeutic
      angiogenesis has yet to be identified, building on the knowledge gained from the
      early pioneering studies may help to identify the best combination.

PMID- 19384085
TI  - Hemolysis associated with prosthetic heart valves: a review.
AB  - Hemolysis is one of the potentially serious complications of prosthetic heart
      valves. It is usually associated with either structural deterioration or
      paravalvular leak. Mild, compensated hemolysis associated with mechanical heart
      valves is not uncommon even in the current era. Severe hemolysis is rare,
      however, and usually reflects paravalvular leak. The use of transesophageal
      echocardiography-guided operative techniques may help prevent or minimize early
      postoperative paravalvular leakage. There is a gamut of available therapeutic
      approaches-medical, transcatheter, and surgical-to this complication and therapy
      should be tailored to the individual patient. Novel pharmacological agents
      include erythropoietin and pentoxifylline. Several reports described the
      feasibility of transcatheter closure of paravalvular leak with coils or devices,
      but their effect on hemolysis is unpredictable. Surgery remains the treatment of
      choice in severe cases.

PMID- 19384086
TI  - Adenosine1 receptor antagonism: a new therapeutic approach for the treatment of
      decompensated heart failure.
AB  - Heart failure (HF) remains a major cause of morbidity and mortality, even with
      the use of standard treatments in patients with chronic HF and acute
      decompensated HF. Impaired renal function is an important prognostic indicator
      for adverse clinical outcomes. Elevated plasma levels of adenosine have been
      observed in HF patients and stimulation of adenosine1 receptors (A1R) in the
      kidney may be contributing to impaired renal function and treatment resistance.
      This observation has led to the development of A1R inhibitor drugs, both in oral
      and intravenous formulations, which in both animal and preliminary clinical
      trials have been shown to augment diuresis while preserving or improving renal
      function in HF patients. An extensive phase III clinical program using the A1R KW
      3902 is now in progress in patients with symptomatic HF and renal dysfunction to
      evaluate the efficacy and safety of this treatment approach.

PMID- 19384087
TI  - Thiazolidinediones and congestive heart failure: a judicious balance of risks and
      benefits.
AB  - Thiazolidinediones are oral antihyperglycemic drugs that have gained significant
      popularity for use in the treatment of type 2 diabetes mellitus. Their insulin
      sensitizing effects lead to better glycemic control, in addition to improvements
      in several cardiovascular parameters independent of blood glucose levels. The
      pleiotropic effects of thiazolidinediones have led to several cardiovascular
      outcome studies, many of which have shown promising data, but some of which bring
      about significant concern. Additionally, the propensity to cause weight gain,
      fluid retention, peripheral edema, and increased risk of heart failure
      hospitalizations continue to pose significant challenges for clinicians using
      these agents in patients with congestive heart failure.

PMID- 19384088
TI  - Treatment of ventricular arrhythmias in the elderly.
AB  - Underlying causes of ventricular tachycardia (VT) or complex ventricular
      arrhythmias (VA) should be treated if possible. Antiarrhythmic drugs should not
      be administered to treat asymptomatic individuals with complex VA and no heart
      disease. Beta-blockers are the only antiarrhythmic drugs that have been
      documented to reduce mortality in patients with VT or complex VA. Radiofrequency
      catheter ablation of VT has been beneficial in treating selected patients with
      arrhythmogenic foci of monomorphic VT. The automatic implantable cardioverter
      defibrillator (AICD) is the most effective treatment for patients with life
      threatening VT or ventricular fibrillation. Patients with AICDs should be treated
      with biventricular pacing, not with dual-chamber rate-responsive pacing at a rate
      of 70/min. Patients with AICDs should also be treated with beta-blockers,
      statins, and angiotensin-converting enzyme inhibitors or angiotensin blockers.

PMID- 19384089
TI  - Clevidipine: a novel ultra-short-acting calcium antagonist.
AB  - Hypertension is the most common cardiovascular condition in the United States. It
      can lead to end organ damage and increased mortality risk if it is not properly
      controlled. In most situations where blood pressure has to be brought down
      quickly, an intravenous agent with a quick onset of action is often used.
      Clevidipine is the first third-generation IV dihydropyridine calcium channel
      blocker that has a high degree of vascular selectivity and an ultra-fast onset
      and offset of blood pressure lowering effect. In various clinical trials,
      clevidipine has shown to be safe and effective in controlling acute blood
      pressure elevations in patients with hypertensive emergencies, preoperative
      hypertension, and postoperative hypertension. The most common adverse events
      noted are atrial fibrillation, nausea, headache, and acute renal failure.
      Overall, clevidipine is a useful addition to available intravenous agents in
      reducing blood pressure during acute situations. The acceptance of this agent to
      hospital formularies may ultimately depend on its perceived ease of
      administration, clinically relevant benefits over other available agents, and
      acquisition costs.

PMID- 19384091
TI  - Lamin A/C deficiency as a cause of familial dilated cardiomyopathy.
AB  - PURPOSE OF REVIEW: Familial dilated cardiomyopathy is an underrecognized form of
      dilated cardiomyopathy. Lamin A/C deficiency is probably the most common cause of
      familial dilated cardiomyopathy. This review will focus on the emerging knowledge
      of epidemiology, diagnosis, and treatment of patients with lamin A/C deficiency,
      as well as possible disease mechanisms. RECENT FINDINGS: Screening of patients
      with dilated cardiomyopathy continues to indicate that lamin A/C deficiency is a
      significant cause. Multiple novel mutations have been found, suggesting that many
      mutations are limited to individuals or families. It is unknown how mutations
      cause the syndrome, although an animal model has shown that lamin A/C
      insufficiency causes apoptosis, particularly in the conduction system.
      Inheritance is predominantly autosomal dominant, but penetrance is variable. For
      symptomatic patients, the course is malignant, with conduction system disease,
      atrial fibrillation, heart failure, and sudden cardiac death. The data are
      contradictory, and currently, there is no clear marker for when a lamin A/C
      deficient patient is at risk for sudden death. SUMMARY: Lamin A/C deficiency is
      an important cause of dilated cardiomyopathy, and diagnosis requires that
      clinicians have a high index of suspicion. Our knowledge of the mechanisms,
      diagnosis, and treatment of lamin A/C deficiency is incomplete. It is clear that
      patients with this condition have a malignant course and need to be followed
      aggressively.

PMID- 19384092
TI  - Beyond the guidelines: where evidence ends and the frontier begins.

PMID- 19384093
TI  - Management of left ventricular assist devices after surgery: bridge, destination,
      and recovery.
AB  - PURPOSE OF REVIEW: As the use and understanding of mechanical circulatory support
      (MCS) increases, the management of these devices has become more conventional.
      The purpose of this review is to discuss the perioperative and long-term
      management of MCS patients. RECENT FINDINGS: With the advent of axial flow pumps,
      both perioperative and long-term management are more standardized. The issues of
      nutrition, physical therapy, drive line care, and readiness to transition to home
      are becoming more mainstream and are readily accepted into the community.
      However, many factors remain that are not well defined in dealing with
      anticoagulation, weaning of MCS, achieving optimal device settings, and end-of
      life care. SUMMARY: Care for the MCS patient provided in a multidisciplinary team
      approach is imperative to allow for a seamless transition from the hospital and
      into the community and successful long-term outcomes.

PMID- 19384094
TI  - Current world literature.
AB  - This bibliography is compiled by clinicians from the journals listed at the end
      of this publication. It is based on literature entered into our database between
      1 January 2008 and 31 December 2008 (articles are generally added to the database
      about two and a half months after publication). In addition, the bibliography
      contains every paper annotated by reviewers; these references were obtained from
      a variety of bibliographic databases and published between the beginning of the
      review period and the time of going to press. The bibliography has been grouped
      into topics that relate to the reviews in this issue.

PMID- 19384095
TI  - HIV infection in the Americas: improving strategic information to improve
      response.

PMID- 19384096
TI  - Epidemiology of HIV in the United States and Canada: current status and ongoing
      challenges.
AB  - PURPOSE: To determine the status of the HIV epidemic in the United States and
      Canada. METHODS: We used data on AIDS and HIV diagnoses for 1996-2005 reported to
      the United States and Canadian national surveillance systems to determine trends
      in AIDS and HIV (33 US states only) diagnoses and to identify population groups
      most affected by HIV. HIV incidence for Canada was determined using back
      calculation methods. We also determined the proportion of persons diagnosed late
      (HIV diagnosis within 12 months before AIDS diagnosis). RESULTS: AIDS diagnosis
      rates were higher in 2005 among blacks (54.1 per 100,000) and Hispanics (18.0)
      compared with whites (5.9) in the United States and among blacks (4.7) and
      aboriginal peoples (4.9) compared with whites (0.7) in Canada. Since 2001, HIV
      diagnoses increased among men who have sex with men in both countries and in
      Canada, increased among persons from HIV-endemic countries and where heterosexual
      contact was the only identified risk of transmission. Overall, HIV incidence
      remained relatively stable in Canada during that period. A large proportion of
      persons were diagnosed late in the disease process (United States, 54.3%; Canada,
      64.2%). CONCLUSIONS: Rates of HIV transmission remain a challenge in both the
      United States and Canada as overall diagnosis rates have not decreased in recent
      years. Renewed prevention efforts are needed to further reduce the high HIV
      diagnosis rates among racial/ethnic minorities and to decrease HIV transmission
      among men who have sex with men.

PMID- 19384097
TI  - Going North: Mexican migrants and their vulnerability to HIV.
AB  - BACKGROUND: Mexican migrants are at higher risk for HIV than Mexicans who do not
      migrate to the United States. Migration to the United States was the driving
      factor of the early Mexican HIV epidemic, and it is likely that it continues to
      strongly influence incidence. An overview of migration of Mexicans to the United
      States identifies many pervasive environmental and structural factors as well as
      risk behaviors that render migrants vulnerable to HIV infection. However,
      published studies sampling Mexicans while in the United States suggest a
      relatively low prevalence of HIV among the general migrant population. To better
      understand this apparent paradox, we sought to identify any demographic variables
      among Mexicans while in Mexico that may indicate that migrants have or acquire
      resources that have a protective effect from their vulnerability due to
      migration. METHODS: A California-Mexico binational collaboration project, with a
      respondent-driven sample with population-based quotas, was conducted in five
      Mexican states from December 2004 to January 2005, in areas with a high index of
      migration to the United States. We compared demographic and behavior variables of
      Mexicans with a history of migration to the United States in the past 12 months
      to nonmigrant Mexicans living in the same community. RESULTS: A total of 1539
      migrants and 1236 nonmigrants were recruited from five Mexican states. Migrants
      (men and women) reported more HIV risk behavior than nonmigrants in the past 12
      months. Migrants reported more sexual partners and noninjected drug use. Migrants
      reported higher condom use during vaginal sex and were more likely to have taken
      an HIV test. CONCLUSION: Though migrants reported higher HIV-related risk
      behaviors, they also reported higher condom use. Migrants were more likely to
      have accessed an HIV test indicating an opportunity for a prevention
      intervention. More binational collaborations are needed to research the different
      levels of vulnerability among Mexican migrants and actual acquisition of HIV
      infection. In addition, more research is needed to identify protective factors
      for HIV prevention interventions among Mexican migrant communities in Mexico and
      in the United States.

PMID- 19384098
TI  - High rates of STD and sexual risk behaviors among Garifunas in Honduras.
AB  - BACKGROUND: Honduras has the highest concentration of HIV and AIDS cases in
      Central America, with an estimated adult HIV prevalence of 1.5%. Prevalence is
      higher among certain ethnic groups such as the Garifuna with a reported HIV
      prevalence of 8%. METHODS: A biological and behavioral survey was conducted on a
      stratified random sample of the Garifuna population in Honduras, using computer
      assisted interviews. Blood was tested for HIV, herpes simplex type 2 (HSV-2), and
      syphilis; urine was tested for Chlamydia trachomatis, Neisseria gonorrhoea,
      Trichomonas vaginalis, and Mycoplasma genitalum. RESULTS: We enrolled a total of
      817 participants, 41% female and 51% male. Estimated prevalences and 95%
      confidence intervals (CI) were: HIV, 4.5% (95% CI: 3.0 to 6.6), HSV-2, 51.1% (95%
      CI: 46.7 to 55.6), and syphilis seropositivity, 2.4% (95% CI: 1.4 to 4.0).
      Sexually transmitted infections in urine were: chlamydia, 6.8% (95% CI: 4.7 to
      9.7), gonorrhea, 1.1% (95% CI: 0.4 to 2.9), trichomoniasis, 10.5% (95% CI: 8.1 to
      13.6), and Mycoplasma genitalium, 7.1% (95% CI: 5.1 to 9.9). Consistent condom
      use was low with stable (10.6%) and casual (41.4%) partners. In multivariate
      analysis, HIV was associated with rural residence. HSV-2 was associated with
      female sex, older age, and syphilis seropositivity. CONCLUSIONS: We found a
      moderate prevalence of HIV and a high prevalence of HSV-2 among the Garifunas.
      HSV-2 may increase the vulnerability of these populations to HIV in the future.
      Intervention strategies should emphasize sexually transmitted infection control
      and condom promotion, specifically targeting the Garifuna population.

PMID- 19384099
TI  - The UALE Project: decline in the incidence of HIV and sexually transmitted
      infections and increase in the use of condoms among sex workers in Guatemala.
AB  - OBJECTIVES: To assess the impact of a multilevel sexually transmitted infections
      (STI)/HIV prevention and treatment intervention on the incidence of STIs and HIV,
      the use of condoms, and HIV knowledge among sex workers (SWs). METHODS: An open
      enrolment cohort of 1554 SWs attending STI clinics integrated within the primary
      health care system of Escuintla, Guatemala. They were offered 6 monthly STI/HIV
      screening, condom promotion, education, and community-based interventions. We
      evaluated trends in condom use, HIV-related knowledge, and STI/HIV incidence
      using generalized estimating equations. RESULTS: For over three and a half years,
      there was a significant increase in the proportion of consistent condom use from
      the baseline visit through the third follow-up visit (94.29%-99.11% with new
      clients and 90.36%-97.22% with regular clients) and in HIV-related knowledge
      (95.99%-97.22%). Except for syphilis, we observed a significant decline in
      gonorrhoea, chlamydia, trichomoniasis, and candidiasis in each follow-up visit,
      from 11.30 per 100 person-years, 10.71 per 100 person-years, 6.88 per 100 person
      years, and 8.23 per 100 person-years in the first follow-up visit to 6.44 per 100
      person-years, 6.21 per 100 person-years, 4.81 per 100 person-years, and 6.17 per
      100 person-years in the third follow-up visit, for each STI, respectively. HIV
      global incidence was 0.41 per 100 person-years, and it significantly declined
      from 1.85 per 100 person-years (2005) to 0.42 per 100 person-years (2008).
      CONCLUSIONS: Although a longer follow-up would be needed, the results suggest
      that the intervention was feasible and has been shown to be effective in reducing
      STI and HIV incidence and in increasing condom use with clients and HIV-related
      knowledge.

PMID- 19384100
TI  - A life course approach to patterns and trends in modern Latin American sexual
      behavior.
AB  - This article explores trends in sexual behavior in Latin America, envisaged from
      a life-course perspective, taking into account social differences. It is focused
      on three main issues: the timing of early sexual and reproductive events, sexual
      activity during adulthood, and measurement of homosexuality-bisexuality. It draws
      on general population data from nonspecific surveys, as surveys dealing
      specifically with sexual behavior are scarce in Latin American countries. A
      traditional feature in these societies is the huge amount of social inequality,
      which translates directly into social differences in sexual experience,
      especially among women. Despite the decline in fertility, an early start of
      unions and of reproductive experience remains typical of groups with lower
      education. Another aspect is the diversity of national patterns and gender
      systems, very far from the image of cultural homogeneity generally associated
      with this region. Data show a low prevalence of homosexuality/bisexuality, which
      can be a result of underreporting. The paper eventually stresses the necessity of
      carrying out more sexual behavior surveys of the general population in the
      region.

PMID- 19384101
TI  - Predictors of sexual risk reduction among Mexican female sex workers enrolled in
      a behavioral intervention study.
AB  - OBJECTIVE: We recently showed efficacy of an intervention to increase condom use
      among female sex workers (FSWs) in Tijuana and Ciudad Juarez, situated on the
      Mexico-United States border. We determined whether increases in condom use were
      predicted by social cognitive theory and injection drug user status among women
      randomized to this intervention. METHODS: Four hundred nine HIV-negative FSWs
      aged >or=18 years having unprotected sex with clients within the prior 2 months
      received a brief individual counseling session integrating motivational
      interviewing and principles of behavior change (ie, HIV knowledge, self-efficacy
      for using condoms, and outcome expectancies). RESULTS: Increases in self-efficacy
      scores were associated with increases in percent condom use (P = 0.008), whereas
      outcome expectancies were not. Female sex workers who inject drugs (FSW-IDUs)
      increased condom use with clients but not to the same extent as other FSWs (P =
      0.09). Change in HIV knowledge was positively associated with change in percent
      condom use among FSW-IDUs (P = 0.03) but not noninjection drug users.
      CONCLUSIONS: Increases in self-efficacy significantly predicted increased condom
      use among FSWs, consistent with social cognitive theory. Increased HIV knowledge
      was also important among FSW-IDUs, but their changes in condom use were modest.
      Enhanced interventions for FSW-IDUs are needed, taking into account realities of
      substance use during sexual transactions that can compromise safer sex
      negotiation.

PMID- 19384102
TI  - High HIV and ulcerative sexually transmitted infection incidence estimates among
      men who have sex with men in Peru: awaiting for an effective preventive
      intervention.
AB  - BACKGROUND: In the Andean Region, HIV and sexually transmitted infections (STI)
      are most prevalent among men who have sex with men (MSM), but incidence estimates
      and associated factors have never been prospectively assessed. METHODS: A cohort
      of 1,056 high-risk HIV-negative MSM in Lima, Peru, were recruited during 1998
      2000 (the ALASKA Cohort), and a nested case-control analysis was conducted
      between seroconverters and nonseroconverters, matched 1:3 by age and duration of
      follow-up for comparison of risk behaviors, acute retroviral symptoms,
      circumcision, and STI. RESULTS: During average follow-up of 335 days, 34 men
      seroconverted, providing a HIV incidence estimate of 3.5 per 100 person-years
      [95% confidence interval (CI): 2.3 to 4.7]. High syphilis (8.4 per 100 person
      years, 95% CI: 6.7 to 10.1) and herpes simplex virus type 2 (HSV-2) infection
      (10.4 per 100 person-years, 95% CI: 8.6 to 11.9) incidence estimates were
      obtained. HIV seroconverters were more likely than men who remained seronegative
      to report fever >or=3 days (46% vs. 7%), to seek medical care (62% vs. 27%), and
      to have >or=1 casual partner (86.2% vs. 74.1%) since their last visit. HIV
      seroconverters also were more likely to have acquired syphilis or HSV-2 infection
      (31% vs. 8% among initially HSV-2-seronegative men) although they were less
      likely to be circumcised (4.2% vs. 20.6%, a nonsignificant difference). In
      multivariate analysis, incident syphilis or HSV-2 infection (odds ratio [OR]:
      5.9, 95% CI: 1.5 to 22.7) and sex with any casual partner (OR: 4.8, 95% CI: 0.9
      to 26.2) were associated with HIV seroconversion. CONCLUSIONS: STI that may cause
      anogenital ulcers are important risk factors for HIV acquisition among high-risk
      MSM in Lima, a population with a very high HIV incidence estimate. Synergistic
      interventions focusing in preventing both HIV and HSV-2, like male circumcision,
      are warranted to be assessed, especially in MSM populations with low levels of
      circumcision and high incidence estimates of ulcerative STI.

PMID- 19384104
TI  - The national response to the HIV/AIDS epidemic in Peru: accomplishments and gaps-
      a review.
AB  - In Peru, after the first case of AIDS was reported in 1983, nearly 20,000 AIDS
      cases have been notified to date and between 20,000 and 79,000 persons are
      estimated to be living with HIV. Despite a relatively low HIV prevalence in the
      general population, the epidemic has importantly mobilized social actors and
      economic resources and has helped articulate a very active field within the
      Peruvian health sector. In recent years, the country has become the largest
      recipient of HIV funding from the Global Fund for AIDS, Tuberculosis, and Malaria
      in Latin America, for which a substantial national counterpart has been
      committed. Peru's predictable selection as one of the 12 focal countries for the
      5-year impact evaluation of the Global Fund suggested that an analysis of the
      response to the HIV epidemic in Peru may provide significant lessons on the
      possibilities of international aid in the AIDS field, particularly in the Latin
      American context. This article presents an analysis of the impact of the HIV/AIDS
      epidemic and the nature of the response articulated by the State and civil
      society in Peru, based on the Universal Access Principles proposed by World
      Health Organization, UNAIDS, and others. Relying on a number of recent secondary
      sources, we focus not only on the impact of the epidemic on morbidity and death
      but also on the changes in society as a whole, particularly in social movements
      and their dynamic relationship with the State. We start with an epidemiological
      overview and move to describe the role of social actors in response to the
      epidemic and then propose a framework for the analysis of the scope and
      limitations of the national response and elaborate on potential courses of action
      that may lead to strengthen accomplishments and resolve remaining gaps.

PMID- 19384103
TI  - Understanding the HIV epidemic in the Dominican Republic: a prevention success
      story in the Caribbean?
AB  - OBJECTIVE: To analyze the general dynamics and trends of the HIV epidemic in the
      Dominican Republic (DR). METHODS: Thorough review of available HIV seroprevalence
      and sexual behavioral data from the DR. RESULTS: Multiple sources of data suggest
      that the DR's HIV epidemic has generally declined. Between the mid-1990s and
      about 2002, HIV-1 prevalence fell among pregnant women in the capital, Santo
      Domingo, particularly among young women. Declines in prevalence were also
      observed over the same period among sexually transmitted infection clinic
      patients, blood bank donors, US entry visa applicants, and female sex workers.
      National household surveys found 1.0% (confidence interval: 0.9% to 1.1%) adult
      prevalence in 2002 and 0.8% (0.6% to 0.9%) in 2007. Among largely Haitian
      immigrant residents of the impoverished former "sugarcane plantations,"
      prevalence was much higher but declined from 5.0% to 3.2% between 2002 and 2007.
      The DR's heterogeneous epidemic includes an important men-having-sex-with-men
      (MSM) and bisexual component. The proportion of reported AIDS cases among men
      remained constant from 1989 to 2006, accounting for about two thirds of both
      total cumulative and year 2006 cases. Some survey and qualitative data also
      suggest a considerable occurrence of MSM-related risk behaviors. HIV prevalence
      remains relatively high in MSM, with no evidence of significant decrease.
      CONCLUSIONS: As in several other developing countries that have succeeded in
      slowing HIV transmission, HIV reductions in the DR seem mainly due to changes in
      sexual behavior, particularly increased condom use, especially for sex work, and
      partner reduction in men. Similarly favorable HIV declines and reported behavior
      change have occurred in some other Caribbean countries, including neighboring
      Haiti. However, of concern is that anal sex, both male-male and heterosexual,
      remains a taboo yet apparently common practice largely ignored by existing
      prevention campaigns. And although the DR epidemic has generally stabilized,
      there is a danger of complacency, and some recent data suggest that HIV
      prevalence is no longer declining (and may even be increasing) in some
      populations.

PMID- 19384105
TI  - Preventing transfusion-transmitted HIV infection in Latin America and the
      Caribbean: issues associated with blood donor interviews and sex between men.
AB  - BACKGROUND: Blood-borne transmission is the most efficient route for acquiring
      HIV infection, particularly through transfusion. Availability of noninfectious
      blood units for hemotherapy is a necessary condition for efficient functioning of
      health services. They have the obligation to ensure that the blood supply is
      safe, which includes interviewing potential donors to ascertain whether they
      might be at risk of being HIV infected. The interview procedures demand that
      blood services staff inquire potential blood donors about sexual practices
      associated to HIV transmission. Assumptions and misconceptions may unnecessary
      exclude adequate donors. METHODS: Review of published and unpublished country
      reports in Latin America regarding blood safety and deferral criteria related to
      same sexual behavior among males. RESULTS: An analysis of criteria for deferral
      of potential blood donors shows inconsistencies that may impact the necessary
      safe blood supply. CONCLUSIONS: The blood donor deferral criteria should be
      revised according to relevant epidemiological evidence and social legitimacy.
      Personnel in blood banks and hemotherapy services should be educated to conduct
      appropriate interviews for accepting or deferring potential donors. Potential
      donors and the public should be knowledgeable for them to understand the reasons
      why some individuals may be deferred. Health authorities should work to reduce
      the stigma associated with HIV, prioritize building strong and meaningful
      partnerships with civil society, and engage diverse sectors in the national AIDS
      response.

PMID- 19384106
TI  - The efficacy of alendronate in wheelchair-bound patients: a 1-year prospective
      study.
AB  - The aim of the study was to establish the efficacy of 1-year alendronate
      treatment in 10 wheelchair-bound participants. In the study were included
      participants with z-score lower than -2.0 in one of three skeletal sites. Bone
      status was assessed using dual-energy X-ray absorptiometry at calcaneus and
      forearm and using quantitative ultrasound at hand phalanges at baseline and after
      a year. Laboratory variables included serum carboxyterminal telopeptide of type I
      collagen (ICTP) and bone alkaline phosphatase. Mean values of bone measurements
      did not differ between baseline and follow-up, the mean value of ICTP
      nonsignificantly increased and bone alkaline phosphatase significantly dropped
      (P<0.01). No patient treated revealed the increase in three bone densitometric
      variables and only one showed a decrease in ICTP exceeding 40% of baseline value.
      Concluding, in wheelchair-bound participants short-term alendronate therapy does
      not reduce bone resorption and does not improve the skeletal status.

PMID- 19384109
TI  - The octuplets tragedy.

PMID- 19384110
TI  - "Whatsoever a [woman] soweth, that shall [she] also reap".

PMID- 19384111
TI  - Duration of lactation and risk factors for maternal cardiovascular disease.
AB  - OBJECTIVE: To examine dose-response relationships between the cumulative number
      of months women lactated and postmenopausal risk factors for cardiovascular
      disease. METHODS: We examined data from 139,681 postmenopausal women (median age
      63 years) who reported at least one live birth on enrolling in the Women's Health
      Initiative observational study or controlled trials. Multivariable models were
      used to control for sociodemographic (age, parity, race, education, income, age
      at menopause), lifestyle, and family history variables when examining the effect
      of duration of lactation on risk factors for cardiovascular disease, including
      obesity (body mass index [BMI] at or above 30), hypertension, self-reported
      diabetes, hyperlipidemia, and prevalent and incident cardiovascular disease.
      RESULTS: Dose-response relationships were seen; in fully adjusted models, women
      who reported a lifetime history of more than 12 months of lactation were less
      likely to have hypertension (odds ratio [OR] 0.88, P<.001), diabetes (OR 0.80,
      P<.001), hyperlipidemia (OR 0.81, P<.001), or cardiovascular disease (OR 0.91,
      P=.008) than women who never breast-fed, but they were not less likely to be
      obese. In models adjusted for all above variables and BMI, similar relationships
      were seen. Using multivariate adjusted prevalence ratios from generalized linear
      models, we estimate that among parous women who did not breast-feed compared with
      those who breast-fed for more than 12 months, 42.1% versus 38.6% would have
      hypertension, 5.3% versus 4.3% would have diabetes, 14.8% versus 12.3% would have
      hyperlipidemia, and 9.9% versus 9.1% would have developed cardiovascular disease
      when postmenopausal. Over an average of 7.9 years of postmenopausal participation
      in the Women's Health Initiative, women with a single live birth who breast-fed
      for 7-12 months were significantly less likely to develop cardiovascular disease
      (hazard ratio 0.72, 95% confidence interval 0.53-0.97) than women who never
      breast-fed. CONCLUSION: Among postmenopausal women, increased duration of
      lactation was associated with a lower prevalence of hypertension, diabetes,
      hyperlipidemia, and cardiovascular disease.

PMID- 19384112
TI  - Epidemiologic and economic effect of methicillin-resistant Staphylococcus aureus
      in obstetrics.
AB  - OBJECTIVE: To quantify the epidemiologic and economic burden of methicillin
      resistant Staphylococcus aureus (MRSA) infections in the obstetric population,
      identify main factors influencing the magnitude of disease, and evaluate the cost
      effectiveness of MRSA screening and decolonization. METHODS: A cost-effectiveness
      decision analytic model was constructed for estimations from both the societal
      and third party-payer perspectives. Probabilities were derived from prior studies
      when available. Cost data came from the Healthcare Cost and Utilization Project,
      medication wholesale prices, and the Centers for Medicare & Medicaid Services.
      Sensitivity analysis was conducted to assess the effect of variables across a
      range of values. RESULTS: Approximately 14,294 pregnant or postpartum women
      experience an invasive MRSA infection in the United States annually. The majority
      of invasive MRSA infections are mastitis (n=8,880). The annual economic effect of
      MRSA infections is projected to be approximately $8.7 million and approximately
      $8.0 million from the societal and payer perspectives, respectively. Sensitivity
      analyses demonstrate that the prevalence of MRSA, incidence of mastitis, and rate
      of cesarean deliveries were key driving factors for the estimations. CONCLUSION:
      Methicillin-resistant S aureus is an important emerging pathogen responsible for
      a modest burden of puerperal infections and associated costs. Universal screening
      and decolonization efforts do not currently seem to be cost-effective.

PMID- 19384113
TI  - Predictors of failed pelvic arterial embolization for severe postpartum
      hemorrhage.
AB  - OBJECTIVES: To estimate what factors are associated with a failed pelvic arterial
      embolization for postpartum hemorrhage and to attempt to estimate efficacy of
      pelvic arterial embolization in rare conditions. METHODS: This was a
      retrospective cohort study including all consecutive women who underwent pelvic
      arterial embolization trial for postpartum hemorrhage between 1994 and 2007 at a
      tertiary care center. Pelvic arterial embolization failure was defined as the
      requirement for subsequent surgical procedure to control postpartum hemorrhage.
      RESULTS: Pelvic arterial embolization was attempted in 0.3% of deliveries by the
      same radiologist in 87% of cases. Failures occurred in 11 of 100 cases (11%) and
      in 4 of 17 cases (24%) of placenta accreta or percreta. The major complication
      rate after pelvic arterial embolization was low (3%). Fifty patients (50%) were
      transferred from nine other institutions. Pelvic arterial embolization was
      performed in 11 cases (11%) after a failed conservative surgical procedure and in
      eight cases (8%) for secondary postpartum hemorrhage, with success rates of 91%
      and 88%, respectively. Pelvic arterial embolization demonstrated a patency
      throughout one ligated pedicle in 9 of the 11 cases of failed conservative
      surgical procedure (82%). Twin pregnancy, chorioamnionitis, operative vaginal
      delivery, hospital-to-hospital transfer, nature of embolizing agent and arteries
      embolized, failed surgical procedure, secondary postpartum hemorrhage, cause of
      postpartum hemorrhage, and more than one pelvic arterial embolization were not
      found to be significantly associated with failed pelvic arterial embolization.
      CONCLUSION: The only factors significantly associated with failed pelvic arterial
      embolization were a higher rate of estimated blood loss (more than 1,500 mL) and
      more than 5 transfused red blood cell units. Attempted pelvic arterial
      embolization after a failed vessel ligation procedure and for a secondary
      postpartum hemorrhage is a good option with high success rates.

PMID- 19384114
TI  - Effect of maternal obesity on the ultrasound detection of anomalous fetuses.
AB  - OBJECTIVE: To estimate the effect of maternal habitus on detection of fetuses
      with major structural anomalies during second-trimester standard and targeted
      ultrasound examinations. METHODS: This was a retrospective cohort study of
      pregnancies 18 to 24 weeks that underwent ultrasonography over a 5-year period.
      An anomalous fetus was considered detected if a major abnormality of the relevant
      organ system was identified, regardless of the anticipated ultrasound detection.
      Anomalies were verified using a prospectively maintained database. Body mass
      index (BMI) was based on weight at first prenatal visit. RESULTS: There were
      10,112 standard examinations in low-risk pregnancies and 1,098 targeted
      examinations in pregnancies with either high-risk indications or with an
      abnormality detected during standard ultrasonography. Detection of anomalous
      fetuses decreased with increasing BMI. For normal BMI, overweight, and class I,
      II, and III obesity, detection with standard ultrasonography was 66%, 49%, 48%,
      42%, and 25%, respectively, and with targeted ultrasonography, 97%, 91%, 75%,
      88%, and 75%, respectively, both P< or =.03. Residual anomaly risk after a normal
      ultrasound examination increased with increasing BMI, from 0.4% among women of
      normal BMI to 1.0% among obese women, P=.001. Anomaly detection was lower among
      women with pregestational diabetes than in those with other high-risk
      indications, 38% compared with 88% respectively, P<.001. CONCLUSION: With
      increasing maternal BMI, we found decreased detection of anomalous fetuses with
      either standard or targeted ultrasonography, a difference of at least 20% when
      women of normal BMI were compared with obese women. Anomaly detection was even
      less in pregnancies complicated by pregestational diabetes. Counseling may need
      to be modified to reflect the limitations of ultrasonography in obese women.

PMID- 19384115
TI  - Associations of unscavenged anesthetic gases and long working hours with preterm
      delivery in female veterinarians.
AB  - OBJECTIVE: To examine whether occupational hazards such as anesthetic gases,
      radiation, pesticides, and working hours in veterinary practice are associated
      with preterm delivery (before 37 weeks of gestation) in female veterinarians.
      METHODS: The Health Risks of Australian Veterinarians project was conducted as a
      questionnaire-based survey of all graduates of Australian veterinary schools
      during the 40-year period 1960-2000. Approximately 1,200 female veterinarians
      participated in the survey. Pregnancy was defined as the unit of analysis. We
      restricted analyses to pregnancies of those women who reported being employed
      when the pregnancy began and were working only in clinical practice. Of 1,355
      pregnancies in total in the file, 744 pregnancies were eligible for the final
      analysis. RESULTS: The prevalence of preterm birth in women exposed to
      unscavenged anesthetic gases was 7.3% compared with 5.7% in the general
      population. In a Cox proportional hazards model controlling for the potential
      confounders, there was a significant 2.5-fold increase (hazard ratio 2.56, 95%
      confidence interval [CI] 1.33-4.91) in the risk of preterm delivery in women
      exposed to unscavenged anesthetic gases for 1 or more hours per week compared
      with the unexposed group (women who did not perform surgery and those who
      performed surgery in the presence of a scavenger system). A dose-response
      relation also was found within this group when exposure was divided into finer
      categories. There was also a strong and monotonic increase in risk of preterm
      delivery and the number of hours worked per week with veterinarians working more
      than 45 hours a week (hazard ratio 3.69, 95% CI 1.40-9.72) compared with those
      working fewer than 45 hours per week. CONCLUSION: Long working hours and
      performing surgery in the absence of a scavenger system for anesthetic gases are
      important risk factors for preterm birth in female veterinarians.

PMID- 19384116
TI  - Cosmetologists and reproductive outcomes.
AB  - OBJECTIVE: To test the hypothesis that cosmetologists are at increased risk of
      poor pregnancy outcomes compared with women of the same age who are not
      cosmetologists. METHODS: Participants were recruited through mass mailing of
      questionnaires. To be included in the study, respondents to the survey had to be
      aged between 21 and 55 years and not have had a hysterectomy or oophorectomy.
      This analysis focused on 350 cosmetologists and 397 women in other occupations
      who met these inclusion criteria and who reported five or fewer singleton
      pregnancies. The main outcome measures were miscarriage, stillbirth, the
      occurrence of maternal health conditions during pregnancy (preeclampsia, high
      blood pressure, diabetes), hospitalization or physician-ordered bed rest during
      pregnancy, preterm labor, and premature delivery (before 37 weeks at delivery).
      RESULTS: There were no statistically significant associations between occupation
      and the pregnancy outcomes after adjustment for age, race, education, and smoking
      and alcohol use at the time of pregnancy. A statistically significant association
      was found between race and low birth weight such that nonwhite women were at
      increased risk of reporting a low birth weight neonate compared with white women
      (odds ratio [OR] 3.35, 95% confidence interval [CI] 1.53-7.26). Similarly,
      current smoking was found to be positively associated with miscarriage (OR 1.53,
      CI 1.09-2.16) and miscarriage or stillbirth (OR 1.64, 95% CI 1.18-2.28).
      CONCLUSION: Risk of adverse pregnancy outcomes among cosmetologists is not
      increased compared with women of the same age working in other occupations.

PMID- 19384117
TI  - Ovarian conservation at the time of hysterectomy and long-term health outcomes in
      the nurses' health study.
AB  - OBJECTIVE: To report long-term health outcomes and mortality after oophorectomy
      or ovarian conservation. METHODS: We conducted a prospective, observational study
      of 29,380 women participants of the Nurses' Health Study who had a hysterectomy
      for benign disease; 16,345 (55.6%) had hysterectomy with bilateral oophorectomy,
      and 13,035 (44.4%) had hysterectomy with ovarian conservation. We evaluated
      incident events or death due to coronary heart disease (CHD), stroke, breast
      cancer, ovarian cancer, lung cancer, colorectal cancer, total cancers, hip
      fracture, pulmonary embolus, and death from all causes. RESULTS: Over 24 years of
      follow-up, for women with hysterectomy and bilateral oophorectomy compared with
      ovarian conservation, the multivariable hazard ratios (HRs) were 1.12 (95%
      confidence interval [CI] 1.03-1.21) for total mortality, 1.17 (95% CI 1.02-1.35)
      for fatal plus nonfatal CHD, and 1.14 (95% CI 0.98-1.33) for stroke. Although the
      risks of breast (HR 0.75, 95% CI 0.68-0.84), ovarian (HR 0.04, 95% CI 0.01-0.09,
      number needed to treat=220), and total cancers (HR 0.90, 95% CI 0.84-0.96)
      decreased after oophorectomy, lung cancer incidence (HR=1.26, 95% CI 1.02-1.56,
      number needed to harm=190), and total cancer mortality (HR=1.17, 95% CI 1.04
      1.32) increased. For those never having used estrogen therapy, bilateral
      oophorectomy before age 50 years was associated with an increased risk of all
      cause mortality, CHD, and stroke. With an approximate 35-year life span after
      surgery, one additional death would be expected for every nine oophorectomies
      performed. CONCLUSION: Compared with ovarian conservation, bilateral oophorectomy
      at the time of hysterectomy for benign disease is associated with a decreased
      risk of breast and ovarian cancer but an increased risk of all-cause mortality,
      fatal and nonfatal coronary heart disease, and lung cancer. In no analysis or age
      group was oophorectomy associated with increased survival.

PMID- 19384118
TI  - Factors affecting risk of mortality in women with vaginal cancer.
AB  - OBJECTIVE: To estimate the current effect of demographics, pathology, and
      treatment on mortality among women with vaginal cancer. METHODS: Using data from
      17 population-based cancer registries that participate in the Surveillance,
      Epidemiology, and End Results program, 2,149 women diagnosed with primary vaginal
      cancer between 1990 and 2004 were identified. The association between various
      demographic factors, tumor characteristics, and treatments and risk of vaginal
      cancer mortality were evaluated using Cox proportional hazards modeling. RESULTS:
      The mean age+/-standard deviation at diagnosis was 65.7+/-14.3 years.
      Approximately 66% of all cases were non-Hispanic whites. Incidence was highest
      among African-American women (1.24 per 100,000 person-years). The 5-year disease
      specific survival was 84% (stage I), 75% (stage II), and 57% (stage III/IV). In a
      multivariate adjusted model, women with tumors greater than 4 cm and advanced
      disease had elevated risks of mortality (hazard ratios 1.71 and 4.67,
      respectively). Compared with women with squamous cell carcinomas, patients with
      vaginal melanoma had a 1.51-fold (95% confidence interval 1.07-2.41) increased
      risk of mortality. Surgery alone as a treatment modality had the lowest risk of
      mortality. The risk of mortality has decreased over time, as women diagnosed
      after 2000 had an adjusted 17% decrease in their risk of death compared with
      women from 1990-1994. CONCLUSION: Stage, tumor size, histology, and treatment
      modality significantly affect a woman's risk of mortality from vaginal cancer.
      There seems to be a survival advantage that is temporally related to the advent
      of chemoradiation.

PMID- 19384119
TI  - Clean intermittent self-catheterization after botulinum neurotoxin type A
      injections: short-term effect on quality of life.
AB  - OBJECTIVE: To investigate the hypothesis that the need for clean intermittent
      self-catheterization after botulinum neurotoxin type A injections is outweighed
      by the efficacy of this treatment, so that clean intermittent self
      catheterization is not a burden for patients with refractory idiopathic detrusor
      overactivity. METHODS: Women undergoing intradetrusor injections of 200 units
      botulinum neurotoxin type A for refractory idiopathic detrusor overactivity were
      evaluated prospectively. Clean intermittent self-catheterization was discussed
      with all patients and its possible need after botulinum neurotoxin type A
      treatment. As indicator of quality of life, lower urinary tract symptom distress
      and effect on daily activities were assessed using the validated Urogenital
      Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) before
      and 4 weeks after receiving botulinum neurotoxin type A injections. RESULTS: Mean
      age of the 65 women was 51 years, and all voided spontaneously before botulinum
      neurotoxin type A injections. After botulinum neurotoxin type A treatment, 28
      (43%) required clean intermittent self-catheterization. Mean UDI-6 and IIQ-7
      scores reduced from 61 to 33 (P<.001) and 62 to 30 (P<.001) in women performing
      clean intermittent self-catheterization and from 60 to 28 (P<.001) and 64 to 25
      (P<.001) in those who did not, respectively. Comparison of quality of life in
      women performing clean intermittent self-catheterization and in those who did not
      revealed no significant differences before and after botulinum neurotoxin type A
      treatment. CONCLUSION: Clean intermittent self-catheterization after botulinum
      neurotoxin type A intradetrusor injections did not impair quality of life in
      appropriately informed and selected women in the short term. All patients should
      be informed of the potential need for clean intermittent self-catheterization
      after botulinum neurotoxin type A injections, and a willingness to do so should
      be a prerequisite for this still unlicensed off-label treatment.

PMID- 19384120
TI  - Paracervical compared with intracervical lidocaine for suction curettage: a
      randomized controlled trial.
AB  - OBJECTIVE: To estimate the efficacy of paracervical compared with intracervical
      administration of local anesthesia during first-trimester suction curettage.
      METHODS: A double-blind, randomized controlled trial comparing paracervical with
      intracervical lidocaine was performed in women undergoing elective first
      trimester suction curettage with conscious sedation. Pain was assessed at
      baseline, with dilation, and with curettage using a 10-cm visual analog scale
      (VAS). Assuming a minimal clinically important difference in pain score of 1.6 cm
      and a mean pain score (+/-standard deviation [SD]) of 4.7 (+/-2.9) cm for
      paracervical block, 120 patients would provide 80% power with an alpha of .05.
      RESULTS: For the 132 women randomly assigned, no significant differences in VAS
      scores (mean+/-SD) were observed between paracervical and intracervical blocks
      during dilation (2.6+/-2.3 compared with 2.8+/-2.2, P=.72) or curettage (3.9+/
      2.9 compared with 3.3+/-2.5, P=.16). CONCLUSION: For women undergoing first
      trimester suction curettage with conscious sedation, there was no clinically
      meaningful difference in pain relief between paracervical and intracervical
      lidocaine. Providers should feel confident that both techniques provide equally
      effective and acceptable analgesia.

PMID- 19384121
TI  - Concurrent dinoprostone and oxytocin for labor induction in term premature
      rupture of membranes: a randomized controlled trial.
AB  - OBJECTIVE: : To estimate the effect of concurrent vaginal dinoprostone and
      oxytocin infusion against oxytocin infusion for labor induction in premature
      rupture of membranes (PROM) on vaginal delivery within 12 hours and patient
      satisfaction. METHODS: : Nulliparas with uncomplicated PROM at term, a Bishop
      score less than or equal to 6, and who required labor induction were recruited
      for a double-blind randomized trial. Participants were randomly assigned to 3-mg
      dinoprostone pessary and oxytocin infusion or placebo and oxytocin infusion. A
      cardiotocogram was performed before induction and maintained to delivery.
      Dinoprostone pessary or placebo was placed in the posterior vaginal fornix.
      Oxytocin intravenous infusion was commenced at 2 milliunits/min and doubled every
      30 minutes to a maximum of 32 milliunits/min. Oxytocin infusion rate was titrated
      to achieve four contractions every 10 minutes. Primary outcomes were vaginal
      delivery within 12 hours and maternal satisfaction with the birth process using a
      visual analog scale (VAS) from 0 to 10 (higher score, greater satisfaction).
      RESULTS: : One hundred fourteen women were available for analysis. Vaginal
      delivery rates within 12 hours were 25 of 57 (43.9%) for concurrent treatment
      compared with 27/57 (47.4%) (relative risk 0.9, 95% confidence interval 0.6-1.4,
      P=.85) for oxytocin only; median VAS was 8 (interquartile range [IQR] 2) compared
      with 8 (IQR 2), P=.38. Uterine hyperstimulation was 14% compared with 5.3%,
      P=.20; overall vaginal delivery rates were 59.6% compared with 64.9%, P=.70; and
      induction to vaginal delivery interval 9.7 hours compared with 9.4 hours P=.75
      for concurrent treatment compared with oxytocin, respectively. There was no
      significant difference for any other outcome. CONCLUSION: : Concurrent vaginal
      dinoprostone and intravenous oxytocin for labor induction of term PROM did not
      expedite delivery or improve patient satisfaction. CLINICAL TRIAL REGISTRATION: :
      Current Controlled Trials, www.controlled-trials.com, ISRCTN74376345 LEVEL OF
      EVIDENCE: : I.

PMID- 19384122
TI  - Early compared with late neuraxial analgesia in nulliparous labor induction: a
      randomized controlled trial.
AB  - OBJECTIVE: To determine whether early initiation of neuraxial analgesia
      (anesthetic[s] placed around the nerves of the central nervous system) compared
      with systemic opioid analgesia, followed later in labor by epidural analgesia,
      increases the rate of cesarean delivery in nulliparas undergoing induction of
      labor. METHODS: Nulliparas undergoing induction of labor who requested analgesia
      when cervical dilation was less than 4 cm participated in the study. Patients
      were randomized to neuraxial (early) or systemic opioid (late) analgesia at the
      first analgesia request. Patient-controlled epidural analgesia was initiated in
      the early group at the second analgesia request and in the late group at cervical
      dilation of 4 cm or greater or at the third analgesia request. The primary
      outcome was the rate of cesarean delivery. RESULTS: The rate of cesarean delivery
      was not different between groups (neuraxial [early] 32.7% compared with systemic
      [late] 31.5%, 95% confidence interval of the difference -3% to 6%, P=.65). A
      sample size of 30,500 would be required to detect a difference at the observed
      rate. There were no differences in the mode of vaginal delivery or Apgar scores.
      Pain scores were significantly lower (median 1 compared with 5 on a 0-10 scale,
      P<.001) and labor duration shorter (median 528 minutes compared with 569 minutes,
      P=.047) in the early group. The incidence of reassuring fetal heart rate tracings
      after analgesia was not different between groups. CONCLUSION: Early-labor
      neuraxial analgesia does not increase the cesarean delivery rate compared with
      late epidural analgesia in nulliparas undergoing induction of labor.

PMID- 19384123
TI  - Overview of maternal morbidity during hospitalization for labor and delivery in
      the United States: 1993-1997 and 2001-2005.
AB  - OBJECTIVE: To assess progress toward meeting the U.S. Healthy People 2010
      objective of reducing the rate of maternal morbidity at delivery hospitalization
      by comparing National Hospital Discharge Survey data from two time periods.
      METHODS: Using data from the National Hospital Discharge Survey, we estimated
      rates of intrapartum morbidity defined by obstetric complications, preexisting
      medical conditions, and cesarean delivery during 2001-2005 and compared them with
      rates published for 1993-1997. We calculated and compared the rates for
      categories of morbidity as well as rates for the summary groups of morbidity.
      RESULTS: Between the two time periods, the rate of obstetric complications
      remained unchanged at 28.6%; the prevalence of preexisting medical conditions at
      delivery increased from 4.1% to 4.9%. Rates of chronic hypertension and
      preeclampsia, gestational and preexisting diabetes, asthma, and postpartum
      hemorrhage increased, whereas rates of third- and fourth-degree lacerations and
      various types of infection decreased. The cesarean delivery rate increased from
      21.8% to 28.3%. CONCLUSION: Between 1993-1997 and 2001-2005, the rate of
      intrapartum morbidity associated with obstetric complications was unchanged and
      the rate of pregnancies complicated by preexisting medical conditions increased.

PMID- 19384124
TI  - Antenatal betamethasone administration alters stress physiology in healthy
      neonates.
AB  - OBJECTIVE: To analyze hypothalamic-pituitary-adrenal axis balance in healthy
      newborns after antenatal betamethasone treatment for lung maturation where
      delivery could be prolonged until or near term. METHODS: In a prospective
      observational study, salivary cortisol and cortisone levels were measured at the
      fourth day of life during resting conditions and in response to a pain-induced
      stress event in 23 neonates with antenatal exposure to a single course of
      betamethasone (2x12 mg) and compared with 40 controls. The mean interval between
      betamethasone treatment and delivery was 60+/-23 days. RESULTS: On day 4 of life,
      neonates in the control group exhibited a significant increase in cortisol and
      cortisone from baseline levels after the stress induction (1.175-2.4 ng/mL for
      cortisol and 11.35-18.15 ng/mL for cortisone [both P<.05]), whereas, in
      betamethasone-exposed neonates, cortisol and cortisone stress response was not
      significantly different from baseline levels (1.39-1.6 ng/mL for cortisone
      [P=.76] and 14.8-17.1 ng/mL for cortisol [P=.69]). No influence of gestational
      age at betamethasone administration (P=.76) or gestational age at delivery
      (P=.71) on stress response patterns was observed in a multiple stepwise
      regression. CONCLUSION: A single course of antenatal betamethasone treatment
      induces a suppression of stress reactivity in healthy newborns.

PMID- 19384125
TI  - Nonobstetric risk factors for symptomatic pelvic organ prolapse.
AB  - OBJECTIVE: To identify possible nonobstetric risk factors for symptomatic pelvic
      organ prolapse in the general female population. METHODS: This was a population
      based, cross-sectional study derived from a sample of 5,489 Stockholm women, 30
      to 79 years old, who answered a validated questionnaire for the identification of
      symptomatic prolapse. The 454 women whose answers indicated the presence of such
      prolapse and the 405 randomly selected control participants with answers that
      gave no indication of prolapse received a 72-item questionnaire, which probed
      into a priori suspected risk factors. Only those women with intact uteri and no
      prior surgery for incontinence or prolapse were included. Multivariable logistic
      regression models estimated prevalence odds ratios (ORs) with 95% confidence
      intervals (CIs). RESULTS: In addition to age and parity, overweight (prevalence
      OR for body mass index [kg/m] 26-30 compared with 19-25 was 1.9, 95% CI 1.2-3.1),
      history of conditions suggestive of deficient connective tissue (varicose
      veins/hernia/hemorrhoids, prevalence OR for positive history compared with no
      history 1.8, 95% CI 1.2-2.8), family history of prolapse (prevalence OR for
      positive history compared with no history 3.3, 95% CI 1.7-6.4), heavy lifting at
      work (prevalence OR for 10 kg or more compared with no heavy lifting 2.0, 95% CI
      1.1-3.6), and presence of constipation, hard stools, or difficult evacuation
      (prevalence OR relative to normal bowel habits 2.1, 95% CI 1.4-3.3) all were
      linked independently, significantly, and positively to the presence of
      symptomatic prolapse. CONCLUSION: In this nonconsulting population, age and
      parity were the dominating risk factors, but significant independent associations
      with markers suggestive of congenital susceptibility (family history and
      conditions signaling weak connective tissue) and nonobstetric strain on the
      pelvic floor (overweight/obesity, heavy lifting, and constipation) imply that
      individual predisposition and lifestyle/environment also may play an important
      role. The causal direction of the association with bowel habits remains
      uncertain, and the link to family history could be partly because of information
      bias.

PMID- 19384126
TI  - Optimal location and orientation of suture placement in abdominal sacrocolpopexy.
AB  - OBJECTIVE: To estimate the strongest location and optimal orientation of suture
      placement in the anterior longitudinal ligament for abdominal sacrocolpopexy in
      female cadavers. METHODS: The anterior longitudinal ligament was exposed below
      the level of the aortic bifurcation in 23 unembalmed female cadavers. To the
      right of midline of the vertebral column, sutures were placed in a horizontal
      orientation into the ligament at the sacral promontory, 1 and 2 cm above (sacral
      promontory+1 and sacral promontory+2), and 1, 2, and 3 cm below (sacral
      promontory-1, sacral promontory-2 and sacral promontory-3). At these same
      locations, but to the left of midline, sutures were placed in a vertical
      orientation. Pull-out force and ligament thickness at each level of testing were
      measured. Data were analyzed using Student t test and repeated measures analysis
      of variance. RESULTS: Sutures (either horizontally or vertically placed) had
      greater pull-out strengths at or above, compared with those placed below, the
      level of the sacral promontory. At sacral promontory and sacral promontory+1,
      there were no differences in the pull-out strengths of the ligament when sutures
      were placed in either orientation. However, horizontally placed sutures had
      significantly greater pull-out strengths than vertically placed sutures at sacral
      promontory+2, sacral promontory-1 and sacral promontory-2. Ligament thickness
      decreased from 2 cm above (mean+/-standard error of the mean sacral promontory+2,
      1.8+/-0.1 mm) to 3 cm below (sacral promontory-3, 1.3+/-0.1 mm) the sacral
      promontory. CONCLUSION: Sutures placed in the anterior longitudinal ligament at
      or above the sacral promontory are more secure than those placed below.
      Horizontally oriented sutures should be considered for mesh attachment below the
      sacral promontory because they are significantly stronger when compared with
      vertically placed sutures.

PMID- 19384127
TI  - Levonorgestrel-releasing intrauterine system and endometrial ablation in heavy
      menstrual bleeding: a systematic review and meta-analysis.
AB  - OBJECTIVE: To compare the effects of the levonorgestrel intrauterine system and
      endometrial ablation in reducing heavy menstrual bleeding. DATA SOURCES: Medline
      and EMBASE were searched online using Ovid up to January 2009, as well as the
      reference lists of published articles, to identify randomized controlled trials
      comparing the levonorgestrel intrauterine system with endometrial ablation in the
      treatment of heavy menstrual bleeding. METHODS OF STUDY SELECTION: This
      systematic review and meta-analysis was restricted to randomized controlled
      trials in which menstrual blood loss was reported using pictorial blood loss
      assessment chart scores. TABULATION, INTEGRATION, AND RESULTS: Six randomized
      controlled trials that included 390 women (levonorgestrel intrauterine system,
      n=196; endometrial ablation, n=194) were retrieved. Three studies pertained to
      first-generation endometrial ablation (manual hysteroscopy) and three to second
      generation endometrial ablation (thermal balloon). Study characteristics and
      quality were recorded for each study. Data on the effect of treatment on
      pictorial blood loss assessment chart scores were abstracted, integrated with
      meta-analysis techniques, and presented as weighted mean differences. Both
      treatment modalities were associated with similar reductions in menstrual blood
      loss after 6 months (weighted mean difference, -31.96 pictorial blood loss
      assessment chart score [95% confidence interval (CI), -65.96 to 2.04]), 12 months
      (weighted mean difference, 7.45 pictorial blood loss assessment chart score [95%
      CI, -12.37 to 27.26]), and 24 months (weighted mean difference, -26.70 pictorial
      blood loss assessment chart score [95% CI, -78.54 to 25.15]). In addition, both
      treatments were generally associated with similar improvements in quality of life
      in five studies that reported this as an outcome. No major complications occurred
      with either treatment modality in these small trials. CONCLUSION: Based on the
      meta-analysis of six randomized clinical trials, the efficacy of the
      levonorgestrel intrauterine system in the management of heavy menstrual bleeding
      appears to have similar therapeutic effects to that of endometrial ablation up to
      2 years after treatment.

PMID- 19384128
TI  - Uterine rupture in second-trimester misoprostol-induced abortion after cesarean
      delivery: a systematic review.
AB  - OBJECTIVE: To determine the risk of uterine rupture when using misoprostol for
      second-trimester abortion in women with a history of cesarean delivery. DATA
      SOURCES: MEDLINE, EMBASE, CINAHL, LILACS, and the Cochrane Library were searched
      systematically for all articles published before September 2008. METHODS OF STUDY
      SELECTION: Sixty-three articles were found using the above data sources. I
      excluded case reports, narrative reviews or commentaries, studies that excluded
      women with a history of cesarean delivery, studies with unrelated outcomes,
      studies not conducted in humans, and studies that were not available in English.
      The remaining 16 studies that described misoprostol use for second-trimester
      abortion in women with a history of cesarean delivery were examined. TABULATION,
      INTEGRATION, AND RESULTS: The number of participants with and without cesarean
      delivery, regimen of medical abortion used, and cases of uterine rupture were
      reviewed. To estimate the risk of uterine rupture in women with prior cesarean
      delivery undergoing second-trimester abortion with misoprostol and number needed
      to harm, I pooled the results of all 16 studies. The risk of uterine rupture in
      women with prior cesarean delivery was 0.28% (95% confidence interval [CI] 0.08
      1.00%). The risk of uterine rupture in women without prior cesarean delivery was
      0.04% (95% CI 0.01-0.20%). Based on these risks, if 414 women with a history of
      cesarean delivery were given misoprostol for second-trimester abortion, one would
      experience uterine rupture. CONCLUSION: The risk of uterine rupture among women
      with a prior cesarean delivery undergoing second-trimester abortion using
      misoprostol is less than 0.3%. This may be acceptable to both patients and
      providers.

PMID- 19384129
TI  - Evaluation and treatment of dyspareunia.
AB  - Dyspareunia affects 8-22% of women at some point during their lives, making it
      one of the most common pain problems in gynecologic practice. A mixture of
      anatomic, endocrine, pathologic, and emotional factors combine to challenge the
      diagnostic, therapeutic, and empathetic skills of the physician. New
      understandings of pain in general require new interpretations concerning the
      origins of pain during intercourse, but also provide new avenues of treatment.
      The outcomes of medical and surgical treatments for common gynecologic problems
      should routinely go beyond measures of coital possibility, to include assessment
      of coital comfort, pleasure, and facilitation of intimacy. This review will
      discuss aspects of dyspareunia, including anatomy and neurophysiology, sexual
      physiology, functional changes, pain in response to disease states, and pain
      after gynecologic surgical procedures.

PMID- 19384130
TI  - "Doctor, what would you do?".
AB  - Patients making difficult choices among therapeutic options often ask their
      physicians what they would do if they were in the same situation. When faced with
      that question, physicians might be concerned that a direct answer could infringe
      on a patient's autonomy by substituting the physician's unique worldview or
      experience for their patients'. However, refusing to answer the question might
      lead a patient to feel unsupported at a difficult time. In this article we
      describe an approach that allows a physician to contribute to the patient's
      decision without inadvertently being coercive. That approach requires physicians
      to meaningfully shape therapeutic options, and assist patients in making
      difficult decisions. It is dependent on the physician being aware of the role of
      both their patients' values, and health values (eg, autonomy, futility) in
      decision making. It also requires an awareness of the force of language, both
      stated and implied, in shaping a patient's choice. To make a good decision, women
      need more than accurate information. They also need to be supported and sense
      empathy and understanding from their physicians and feel cared for. Although the
      facts (benefits and harms related to any given choice) are a necessary component
      of counseling, without discussion of values, they do not lead to a truly informed
      decision.

PMID- 19384131
TI  - Time out for a mnemonic.

PMID- 19384132
TI  - Ephraim McDowell and Jane Todd Crawford: the bicentennial of a surgical
      masterpiece.

PMID- 19384133
TI  - The day I made a difference.

PMID- 19384135
TI  - Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer.

PMID- 19384143
TI  - Removing the cervix at hysterectomy: an unnecessary intervention?

PMID- 19384145
TI  - Urethral prolapse in a premenarchal Asian girl.

PMID- 19384147
TI  - Female cosmetic genital surgery.

PMID- 19384149
TI  - ACOG practice bulletin No. 104: antibiotic prophylaxis for gynecologic
      procedures.

PMID- 19384150
TI  - ACOG committee opinion No. 431: routine pelvic examination and cervical cytology
      screening.

PMID- 19384151
TI  - ACOG committee opinion No. 432: spinal muscular atrophy.

PMID- 19384152
TI  - ACOG committee opinion No. 433: optimal goals for anesthesia care in obstetrics.

PMID- 19384153
TI  - Molecular and cellular aspects of hepatitis C virus reinfection after liver
      transplantation: how the early phase impacts on outcomes.
AB  - Hepatitis C virus (HCV)-related liver disease postliver transplantation is
      associated with an accelerated course in comparison with that observed in the
      nonimmunosuppressed individual. Outcomes in transplantation for this indication
      have, therefore, been a major area of clinical interest in the field of liver
      transplantation. The factors underlying the rapid progression of HCV-related
      liver disease posttransplantation are complex and multifactorial. Nevertheless,
      recent data indicate a range of parameters assessable early posttransplantation
      that may be useful in the prediction of outcome of transplantation for this
      condition. This overview, therefore, concentrates on the early events occurring
      postliver transplantation in the HCV-infected patient, and the implications of
      these recent observations for the pathogenesis of the various forms of HCV
      related allograft injury.

PMID- 19384154
TI  - A call for standardization of antireflux surgery in the lung transplantation
      population.
AB  - Long-term survival post lung transplant is reduced significantly by Bronchiolitis
      Obliterans Syndrome. It is suggested that extra-esophageal reflux disease is a
      risk factor for Bronchiolitis Obliterans Syndrome and that antireflux surgery may
      be beneficial. However, practice between centers varies greatly. We suggest a
      need for improved evidence and standardization.

PMID- 19384155
TI  - Obesity and renal transplantation: is bariatric surgery the answer?

PMID- 19384156
TI  - Cold ischemia does not interfere with tolerance induction.
AB  - BACKGROUND: Ischemia/reperfusion injury activates innate immunity, which in turn
      may prevent tolerance induction. We asked whether prolonged cold ischemia
      interferes with successful tolerance induction. METHODS: Kidneys from Dark Agouti
      donors were grafted into binephrectomized Lewis rats after short (20 min) or
      prolonged (6 hr) cold ischemia. Tolerance was induced by nondepleting anti-CD4
      monoclonal antibody RIB 5/2 (10 mg/kg for 5 days). Binephrectomized untreated and
      cytotoxic T-lymphocyte antigen (CTLA)-4Ig treated recipients served as controls.
      Animals were followed for 100 days. Adoptive transfer experiments into
      sublethally irradiated naive Lewis were performed at day 100. Animals received
      kidneys from Dark Agouti rats subsequently without further immunosuppression and
      were followed for an additional 20 days. RESULTS: All RIB 5/2-treated recipients
      survived the first observation period independent of the cold ischemia time.
      Graft function, morphology, and transferred T-cell numbers were comparable in
      both groups. Twenty days after transfer amounts of intragraft and peripheral
      donor-derived cells were significantly reduced in recipients of the initially
      prolonged cold ischemia group associated with an attenuated immune response.
      CONCLUSIONS: Our results prove that an initially extended cold ischemia does not
      interfere with tolerance induced by RIB 5/2. Moreover, we conclude that a
      "tolerizing conditioning" achieved by prolonged cold ischemia during the
      tolerance-induction phase may reduce the immune response in recipients of an
      adoptive cell transfer.

PMID- 19384157
TI  - Identification and characterization of major proteins carrying ABO blood group
      antigens in the human kidney.
AB  - BACKGROUND: It is generally admitted that ABO(H) blood group antigens are linked
      to lipids and proteins. Although glycolipids carrying ABO antigens have been well
      characterized in human kidneys, glycoproteins carrying ABO antigens are largely
      unknown, and their molecular properties remain to be elucidated. METHODS: All the
      blood group A antigen-linked proteins in human kidney could be solubilized and
      captured on immobilized Helix pomatia lectin that recognizes A antigens. These
      proteins were separated on SDS-PAGE gels. The gel pieces containing protein bands
      immunoreactive with anti-A antibody were excised, in-gel digested with trypsin,
      and analyzed by nanoLC tandem mass spectrometer. Protein candidates that carry
      ABO antigens were confirmed by immunoprecipitation and double-labeled
      immunofluorescense microscopy. RESULTS: All the glycoproteins carrying ABO
      antigens were found to be Asn-linked glycoproteins, and presented as multiple
      bands on SDS-PAGE with molecular masses ranging from 60 to 270 kDa. The protein
      bands were subjected for mass spectrometric analysis, which identified 121
      distinct proteins with high confidence. Of the identified proteins, 55 N
      glycosylated, membrane proteins were selected as glycoprotein candidates that
      carry ABO antigens. Among them, most abundantly expressed proteins as estimated
      by the number of peptide matches in the MS spectrometric analysis, such as
      platelet endothelial cell adhesion molecule 1, plasmalemmal vesicle-associated
      protein, and von Willebrand factor, were further characterized. CONCLUSIONS:
      Several glycoproteins were identified that represented major glycoproteins
      carrying ABO antigens in the human kidney, which exhibited distinct features in
      localization to most of vascular endothelial cells.

PMID- 19384158
TI  - Extracorporeal photopheresis efficiently impairs the proinflammatory capacity of
      human 6-sulfo LacNAc dendritic cells.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) emerged as a promising treatment
      modality for steroid-refractory graft-versus-host disease (GVHD), which
      represents a major complication of allogeneic hematopoietic stem-cell
      transplantation. Dendritic cells (DCs) display an extraordinary capacity to
      induce T-cell responses and play a crucial role in the initiation and
      maintainance of GVHD. This study evaluated the direct impact of ECP on the
      proinflammatory capacity of 6-sulfo LacNAc (slan) DCs, representing a major
      subpopulation of human blood DCs. METHODS: SlanDCs were isolated from ECP-treated
      or untreated blood of healthy donors or GVHD patients by immunomagnetic
      isolation. The maturation of slanDC was determined by flow cytometry. Cytokine
      production of slanDCs was measured by enzyme-linked immunosorbent assay. SlanDC
      mediated T-cell proliferation was evaluated by H-thymidine incorporation. SlanDC
      mediated T-cell programming was determined by flow cytometry. RESULTS: ECP
      efficiently impairs the spontaneous maturation and secretion of proinflammatory
      tumor necrosis factor-alpha, interleukin-1beta, and interleukin-12 by slanDCs.
      Furthermore, ECP markedly inhibits slanDC-induced proliferation of CD4 and CD8 T
      cells and polarization of naive CD4 T lymphocytes into Th1 cells. CONCLUSIONS:
      These novel findings indicate that ECP efficiently impairs the proinflammatory
      capacity of slanDCs, which may represent an important mechanism for the
      therapeutic efficiency of ECP in GVHD.

PMID- 19384159
TI  - Primary graft dysfunction in lung transplantation: the role of
      CD26/dipeptidylpeptidase IV and vasoactive intestinal peptide.
AB  - BACKGROUND: Enzymatic activity inhibition of CD26/dipeptidylpeptidase IV
      (CD26/DPP IV) attenuated short-term post-Tx (transplantation) ischemia
      reperfusion injury after 18-hr-ischemia. Here, we investigated the effect of
      intragraft CD26/DPP IV catalytic inhibition on primary graft dysfunction during 7
      day post-Tx, following extended ischemia. METHODS: A syngeneic rat (LEW [Lewis
      abstract]) orthotopic lung Tx model was used, grafts exposed to 18 hr cold
      ischemia before Tx. Controls were flushed and preserved in Perfadex, and
      harvested after 1 day (CON1) or 7 day (CON7) post-Tx. Investigational groups IN1,
      IN3, and IN7 grafts were perfused with and stored in Perfadex + inhibitor (AB192)
      and harvested at 1, 3, and 7 days post-Tx, respectively. Blood gas analysis, peak
      airway pressure (PAwP), wet/dry weight ratio, myeloperoxidase thiobarbituric acid
      reactive substances (TBARS), and staining for vasoactive intestinal peptide (VIP)
      were analyzed. RESULTS: IN1 versus CON1 showed preserved histology, increased pO2
      (P<0.01), lowered PAwP (P<0.01), less edema (P<0.05) and decreased TBARS
      (P<0.05). Survival was better for IN7 versus CON7 (P<0.01). The course of AB192
      perfused grafts from 1 to 7 days displayed improved values for pO2 (P<0.01), PAwP
      (P<0.01), edema (P<0.05), TBARS (P<0.05), and myeloperoxidase (P<0.05). Compared
      with controls, VIP was preserved during 18 hr ischemia in alveolar macrophages
      (P=0.0001) and respiratory epithelial cells (P=0.001). CONCLUSIONS: Perfusion
      with an inhibitor of CD26/DPP IV enzymatic activity significantly reduced the
      incidence and severity of pulmonary primary graft dysfunction and enabled
      recovery after extended ischemia. This is the first report that CD26/DPPIV
      inhibitor treatment increases local pulmonary VIP levels, which correlate with
      preserved ventilatory function and pulmonary structural integrity.

PMID- 19384160
TI  - Potential feasibility of early bone marrow cell injection into the spleen for
      creating functional hepatocytes.
AB  - BACKGROUND: Bone marrow cells (BMCs) are believed to have the ability to generate
      functional hepatocytes and have some merits as a therapeutic modality for
      metabolic liver diseases. However, the appearance of BMC-derived hepatocytes
      (BMDHs) is low. We hypothesized that early BMC injection would be feasible for
      creating BMDHs for two main reasons: (1) the liver is a hematopoietic organ in
      neonatal rats and (2) it may allow sufficient time to generate more BMDHs before
      severe liver injury occurs. METHODS: We used Long Evans Cinnamon (LEC) rats as
      recipients, a model of (1) Wilson disease and (2) liver carcinogenesis. Green
      fluorescent protein-expressing BMCs were injected into newborn LEC rats through
      the spleen. The oxidative activity of ceruloplasmin, which is low in LEC rats,
      was measured to evaluate the treatment. In addition, we performed fluorescence in
      situ hybridization to clarify the origin of the BMDHs and immunohistochemical
      analysis to confirm whether these BMDHs had malignant potential. RESULTS: At 18
      months after injection, we found some green fluorescent protein-expressing areas
      macroscopically in the liver of treated LEC rats. The oxidative activity of
      ceruloplasmin increased in treated LEC rats (n=7) and were much higher than that
      in untreated LEC rats (P=0.015). Moreover, we confirmed that the BMDHs were
      generated by cell fusion and was not detected in any of the neoplastic lesions or
      cholngiofibrotic regions. CONCLUSION: Our results suggest that this novel
      strategy for creating BMDHs is effective and safe.

PMID- 19384161
TI  - Uridine-5'-triphosphate protects against hepatic- ischemic/reperfusion injury in
      mice.
AB  - BACKGROUND AND AIM: Mitochondrial calcium overload triggers apoptosis and also
      regulates ATP production. ATP and uridine-5'-triphosphate (UTP) depletion from
      hepatic tissue after ischemia causes cell death. ATP and UTP binds to cell
      membranes of the hepatocytes through P2Y receptors. Our aim was to investigate
      the role of UTP on the hepatic injury induced by ischemia. METHODS: Isolated
      mouse livers were randomly divided into five groups: (1) control group; (2)
      ischemic group (90 min); (3) as group 2, but with the administration of UTP; (4)
      as group 2, but with the administration of suramin, a P2Y antagonist; and (5) as
      group 3, but with the simultaneous administration of suramin and UTP. RESULTS:
      There was a postischemic significant reduction in the release of liver enzymes in
      the animals pretreated with UTP, the intrahepatic caspase-3 activity was
      significantly decreased, and the intrahepatic ATP content increased compared with
      group 2 (ischemic untreated). UTP prevented intracellular Ca overload after
      hypoxia in hepatocyte cultures. In the UTP-treated groups, significantly fewer
      apoptotic hepatocyte cells were noted by weaker activation of caspase-3 and by
      the transferase-mediated dUTP nick end labeling assay. The administration of
      suramin prevented the beneficial effect of endogenous ATP. UTP treatment
      attenuated the degradation of IkappaBalpha (nuclear factor-kappaB inhibitor) by
      80% during reperfusion with no effect on c-Jun N terminal kinase phosphorylation.
      CONCLUSION: The administration of UTP before induction of ischemia-reperfusion
      can attenuate hepatic injury. UTP administration decreased cytosolic Ca overload
      in hypoxic conditions. UTP-mediated protective effects may be regulated through
      nuclear factor- kappaB inactivation. These findings have important implications
      for the potential use of UTP in ischemic hepatic injury.

PMID- 19384162
TI  - Assessment of cadaveric organ viability during pulsatile perfusion using infrared
      imaging.
AB  - Assessment of pulsatile perfusion (PP) is limited to measurements of flow (V) and
      resistance (R). We investigated infrared (IR) imaging during PP as a means for
      precise organ assessment. IR was used to monitor 10 porcine kidneys during 18 hr
      of PP in an uncontrolled Donation after Cardiac Death model. An IR camera
      (Lockheed Martin) was focused on the anterior surfaces of the kidneys. The degree
      of temperature homogeneity was compared with standard measurements of V and R. IR
      thermal images correlated with V and R (R=0.92, P<0.001). IR detected an increase
      in homogeneity during PP by comparing standard deviation differences before and
      after PP (P=0.002), which was not evident by standard measurements of V and R.
      Finally, IR assessment allowed for measurement of dynamic changes in perfusion.

PMID- 19384164
TI  - Liver transplantation using young pediatric donor grafts in adults with hepatitis
      C infection.
AB  - BACKGROUND: The impact of using grafts from donor's age less than or equal to 13
      years on adult hepatitis C virus (HCV) recipients in terms of survival and HCV
      recurrence is undefined. To determine if adults undergoing liver transplantation
      for HCV who receive a graft from a donor age less than or equal to 13 years have
      similar outcomes to recipients of organs from 18- to 35-year-old donors. METHODS:
      Records from adult HCV patients undergoing liver transplantation between April
      1998 and April 2004 who received whole grafts from non-HCV donors less than 35
      years old after brain death were reviewed. Patients with donor age less than or
      equal to 13 years (group 1) and 18 to 35 years (group 2) were compared for
      patient and graft survival, allograft rejection, biliary complications, and HCV
      recurrence. RESULTS: Fifty-one HCV patients were analyzed. The two groups were
      similar except that group 1 donors and recipients were smaller in size. One year
      patient and graft survival for groups 1 vs. 2 were 93% vs. 94% and 93% vs. 83%,
      respectively (P=NS). Biliary complications, HCV recurrence, and advanced fibrosis
      free survival were not significantly different. CONCLUSION: Whole liver grafts
      from donors age less than or equal to 13 years can potentially be used in
      selected size-matched adult HCV patients in the absence of an acceptable
      pediatric recipient.

PMID- 19384163
TI  - Bariatric surgery among kidney transplant candidates and recipients: analysis of
      the United States renal data system and literature review.
AB  - BACKGROUND: Limited data exist on the safety and efficacy of bariatric surgery
      (BS) in patients with kidney failure. METHODS: We examined Medicare billing
      claims within USRDS registry data (1991-2004) to identify BS cases among renal
      allograft candidates and recipients. RESULTS: Of 188 BS cases, 72 were performed
      pre-listing, 29 on the waitlist, and 87 post-transplant. Roux-en-Y gastric bypass
      was the most common procedure. Thirty-day mortality after BS performed on the
      waitlist and post-transplant was 3.5%, and one transplant recipient lost their
      graft within 30 days after BS. BMI data were available for a subset and suggested
      median excess body weight loss of 31%-61%. Comparison to published clinical
      trials of BS in populations without kidney disease indicates comparable weight
      loss but higher post-BS mortality in the USRDS sample. CONCLUSIONS: Given the
      substantial contributions of obesity to excess morbidity and mortality, BS
      warrants prospective study as a strategy for improving outcomes before and after
      kidney transplantation.

PMID- 19384165
TI  - Increasing utilization of human T-cell lymphotropic virus (+) donors in liver
      transplantation: is it safe?
AB  - BACKGROUND: Liver transplantation is the best treatment option for endstage liver
      disease. The human T-cell lymphotrophic virus (HTLV) has been associated with
      leukemia/lymphoma and progressive neurologic disease. There has, however, been an
      increased utilization of HTLV (+) grafts with little data available to support or
      discourage their use. METHODS: We performed univariate and multivariate analyses
      related to graft and patient survival for recipients of HTLV (+) donors and
      compared them with recipients of HTLV (-) donors using the United Network for
      Organ Sharing database. Complete analysis of recipient and donor clinical and
      demographic factors was performed. RESULTS: There were 81 adult recipients of
      HTLV (+) donors and 29,747 HTLV (-) donor recipients. HTLV (+) donors were more
      likely to be older, women, and black, with a higher average donor risk index and
      creatinine, and were more likely to be shared nationally. Recipients of HTLV (+)
      organs were at slightly elevated risk of graft failure (HR=1.39, 95% CI 0.91
      2.11) and death (HR=1.20, CI 0.71-2.02) relative to HTLV (-) donor recipients
      (P=0.12 and 0.5, respectively). The risk decreased after multivariate analysis -
      graft survival (HR=1.20, CI 0.79-1.83) and patient survival (HR=1.06, CI 0.63
      1.79). CONCLUSION: Our analysis reveals no statistically significant difference
      in graft or patient survival between recipients of HTLV (+) and (-) donors.
      Serious limitations of these data are that serologic testing for HTLV has a high
      false positive rate and that there was a short follow-up period. Until these
      issues are addressed, extreme caution should be exercised when using these
      organs.

PMID- 19384166
TI  - Inadequate immune regulatory function of CD4+CD25bright+FoxP3+ T cells in heart
      transplant patients who experience acute cellular rejection.
AB  - BACKGROUND: CD4CD25FoxP3 regulatory T cells are suppressors of antigen-activated
      immune reactivity. Here, we assessed the clinically relevant role of these cells
      in the control of immune responses directed to a transplanted heart. METHODS: We
      investigated the phenotype and function of peripheral CD4CD25FoxP3 T cells in
      heart transplant patients free from acute rejections (n=9) and in rejectors
      (n=12) before and during acute cellular rejection. RESULTS: Between rejectors and
      nonrejectors, the proportion of CD4CD25 T cells and of FoxP3 cells within this
      population was comparable. Yet, CD4CD25FoxP3 T cells of rejectors had a higher
      CD127 expression than those of nonrejectors (P<0.0001). Depletion of CD4CD25 T
      cells from peripheral blood mononuclear cells increased the antidonor
      proliferative response of both nonrejectors (P=0.0005) and rejectors (P=0.03). In
      rejectors, however, only a 2-fold increase was measured, whereas the
      nonrejectors' response became 14 times higher (P=0.002). Reconstitution of
      CD4CD25 T cells only suppressed the overall antidonor proliferative response of
      CD25 responder cells of nonrejectors significantly (P=0.001). Moreover, the
      percentage inhibition of the response was higher in nonrejectors than in
      rejectors (P=0.02). Analyses of pretransplant samples revealed that CD4CD25 T
      cells of rejectors already had a lower suppressive capacity than those of
      nonrejectors before transplantation (P=0.04). CONCLUSION: CD4CD25FoxP3 T cells of
      heart transplant patients who experience acute rejection had an up-regulated
      CD127 expression and an inadequate regulatory function compared with those of
      nonrejecting patients. Our observations suggest that the function of circulating
      CD4CD25FoxP3 regulatory T cells may be pivotal for the prevention of acute
      cellular rejection after clinical heart transplantation.

PMID- 19384167
TI  - Outcomes of transplantation using kidneys from donors meeting expanded criteria
      in Australia and New Zealand, 1991 to 2005.
AB  - BACKGROUND: Kidneys from expanded criteria donors (ECD) are reported to have
      inferior transplant outcomes. METHODS: Using the Australia and New Zealand
      Dialysis and Transplant Registry, we reviewed deceased donor kidneys transplanted
      from 1991 to 2005 in Australia and New Zealand, followed until December 2006. ECD
      was defined using United Network for Organ Sharing criteria. Graft and patient
      outcomes, estimated glomerular filtration rates (eGFR), acute rejection, and
      delayed graft function were analyzed by donor-age and ECD status, with adjustment
      for important covariates. RESULTS: There were 3248 recipients of non-ECD kidneys
      and 781 recipients of ECD kidneys. Compared with donors aged less than 50 years,
      adjusted hazard ratios for graft failure (GF) at 0 to 1 and 1 to 5 years for ECD
      kidneys from donors aged 60 years or above were 1.92 (1.48-2.49; P<0.001) and
      2.52 (1.97-3.23; P<0.001). The hazard ratios for GF were 1.87 (1.31-2.70; P<0.05)
      for ECD kidneys from donors aged 50 to 59 years in the first year but were not
      increased subsequently. Mean eGFR at 1 year decreased with increasing donor age
      and ECD status (56.4 [53.8-58.9] mL/min for kidneys from donors aged <50, 46.6
      [45.0-48.3] and 43.5 [41.1-45.9] for non-ECD and ECD donors aged 50 to 59 years,
      respectively, and 38.6 [36.9-40.4] for donors > or =60; P<0.001) but subsequent
      eGFR loss was similar except for donors aged 60 years or above (P=0.021). Acute
      rejection and delayed graft function were more frequent in ECD kidney recipients,
      but the associations between GF and donor age/ECD status were independent of
      these factors. CONCLUSIONS: For recipients of ECD kidneys, donor age 60 years or
      above is the most significant determinant of poor outcome; donor age 50 to 59
      years represents a category of intermediate risk.

PMID- 19384168
TI  - Health-related quality of life of patients receiving low-toxicity
      immunosuppressive regimens: a substudy of the Symphony Study.
AB  - OBJECTIVE: To evaluate health-related quality of life (HRQoL) in patients with
      different low-toxicity regimens posttransplantation. METHODS: One hundred fifty
      six patients were randomized to standard-dose cyclosporine A (CsA), mycophenolate
      mofetil, and corticosteroids or daclizumab induction, mycophenolate mofetil, and
      corticosteroids with a low dose of CsA, tacrolimus (Low-Tac), or sirolimus. SF-36
      Health survey was completed at baseline, 3, 6, and 12 months. RESULTS: There were
      no differences between groups in SF-36 at baseline or at month 12. Low-Tac showed
      higher scores at month 3 than standard-dose CsA and low dose of CsA. Patients
      with serum creatinine less than or equal to 1.5 mg/mL had better HRQoL at 6 and
      12 months. Proportion of these patients was higher in Low-Tac at 6 months.
      Physical component summary of Patients increased during follow-up, but mental
      component summary did not. Patients with acute rejection showed lower mental
      component summary at 6 months. CONCLUSIONS: No HRQoL differences were identified
      among groups, but the low-dose Tac group showed the fastest improvement.

PMID- 19384169
TI  - Outcome of third renal allograft retransplants versus primary transplants from
      paired donors.
AB  - BACKGROUND: Third kidney retransplants have technical and immunologic hurdles
      that may preclude success, which is of particular importance in the contemporary
      context of discrepancy between organ supply and demand. METHODS: The outcomes of
      third renal transplant recipients (TRTR) were compared with those receiving a
      first transplant from paired donor kidneys to assess transplant success and
      complication rates. The Ontario-based Trillium Gift of Life Network database was
      used to identify deceased donors (n=28) who donated one kidney to a TRTR and the
      mate kidney to a primary renal transplant recipient (PRTR) from June 1977 to
      August 2006. RESULTS: As anticipated, TRTR were sensitized versus PRTR based on %
      panel reactive antibodies (24%+/-34% vs. 7%+/-14%, P=0.03). Delayed graft
      function (46% vs. 22%, P=0.05) and biopsy-proven rejection episodes (50% vs. 29%,
      P=0.01) occurred more frequently with TRTR despite greater frequency of induction
      therapy (74% vs. 35%, P=0.004). However, 1- and 5-year patient survival were
      similar at 93%, 83% and 96%, 87% for TRTR and PRTR, respectively. Accordingly, 1-
      and 5-year allograft survival censored for mortality, were comparable at 78%, 66%
      and 78%, 75%. Renal function was similar in both groups. Bacterial infections
      (43% vs. 18%, P=0.001) and wound problems (28% vs. 11%, P=0.09) were the only
      postoperative complications to occur more frequently in the TRTR. CONCLUSION: We
      conclude that third renal transplantation should not be discouraged based on
      functional outcomes alone.

PMID- 19384170
TI  - Rimonabant affects cyclosporine a, but not tacrolimus pharmacokinetics in renal
      transplant recipients.
AB  - BACKGROUND: Obesity is a common problem following renal transplantation.
      Rimonabant, a cannabinoid-1 receptor blocker, offers a new approach for reducing
      obesity. METHODS: The potential pharmacokinetic interaction between rimonabant
      and cyclosporine A (CsA, n=10) and tacrolimus (Tac, n=8) was assessed in stable
      renal transplant recipients 6.2 (0.9-21.7) years posttransplant. A 12-hour
      pharmacokinetic profile was obtained before and after two months of concomitant
      treatment with 20 mg rimonabant each morning. RESULTS: Rimonabant treatment
      induced a moderate, but significant increase in CsA AUC0-12 (19.8+/-16.1 %,
      P=0.005). Cmax and C2 values tended to increase whereas C0 remained unaffected.
      Tac pharmacokinetics was not significantly affected by rimonabant treatment.
      Eleven of 18 patients experienced adverse events. Two patients reported
      depressions and one reported severe nightmares. CONCLUSIONS: The effect on CsA
      pharmacokinetics is probably of marginal clinical relevance since trough
      concentrations were unaltered, but CsA concentrations should probably be more
      closely monitored if rimonabant treatment is initiated, preferably by C2
      monitoring.

PMID- 19384171
TI  - Tacrolimus concentrations in relation to CYP3A and ABCB1 polymorphisms among
      solid organ transplant recipients in Korea.
AB  - BACKGROUND: Cytochrome P450 3A (CYP3A) and the drug transporter P-glycoprotein (P
      gp) affect the bioavailability of tacrolimus, the most commonly used
      immunosuppressive agent in organ transplant recipients. We have determined the
      genotypic frequencies of the CYP3A and ATP-binding cassette sub-family B member 1
      (ABCB1) genes, which encode the CYP3A and P-gp proteins, respectively, in Korean
      organ transplant recipients and donors, and have assessed the influence of CYP3A
      and ABCB1 polymorphisms on tacrolimus concentrations. METHODS: Using chip-based
      MALDI-TOF mass spectrometry, 506 solid organ transplant recipients and 62
      corresponding of liver transplant donors were genotyped for CYP3A4*6, CYP3A4*18,
      CYP3A5*3, CYP3A5P1*3, ABCB1 c.2677G>A/T, and ABCB1 c.3435C>T alleles, and their
      steady-state blood concentrations of tacrolimus were measured. RESULTS:
      Frequencies of variant alleles among the transplant recipients were CYP3A5*3
      76.8%, CYP3A5P1*3 75.9%, ABCB1 c.2677A/T 52.8%, ABCB1 c.3435T 36.9%, CYP3A4*18
      1.9%, and CYP3A4*6 0.3%. The CYP3A5P1*3 allele was strongly linked to the
      CYP3A5*3 allele (r=0.816). Patients with the CYP3A5*3 and CYP3A5P1*3 alleles
      showed higher blood tacrolimus concentrations per adjusted dose ratio than did
      patients with wild-type alleles, among both liver transplant donors and renal
      transplant recipients. CONCLUSION: The CYP3A5 genotype of the liver is considered
      to show the most important association with tacrolimus concentrations.
      Ultimately, genotyping for CYP3A5 may help optimal individualization of
      immunosuppressive drug therapy for patients undergoing solid organ
      transplantation.

PMID- 19384172
TI  - Kidney transplantation for primary focal segmental glomerulosclerosis: outcomes
      and response to therapy for recurrence.
AB  - BACKGROUND: For a subset of adults and children with primary focal segmental
      glomerulosclerosis (FSGS), proteinuria and renal dysfunction recur after kidney
      transplantation (KTx). Predicting recurrence and response to plasmapheresis (PP)
      or other interventions remains problematic. METHODS: The prevalence, recurrence
      rate, outcomes, and treatment responses of patients with FSGS were determined
      among 1573 KTx recipients. Although 5.0% carried some diagnosis of FSGS, only
      1.9% (n=30) met strict diagnostic criteria for primary FSGS including biopsy
      proven FSGS, lack of secondary factors, negative family history, and progression
      to end-stage renal disease within 10 years. RESULTS: Of these, 47% had recurrent
      FSGS compared with 8% of those not meeting strict criteria (P<0.001). Recurrence
      was more common in children compared with adults (86% vs. 35%, P=0.01). Graft
      survival was lower for recipients with primary FSGS compared with all others and
      inferior graft survival was attributable to recurrent FSGS. Fourteen patients
      received PP preemptively (pre-KTx) or therapeutically (post-KTx) for recurrent
      disease. Four pediatric patients additionally received anti-CD20 (rituximab)
      therapy. Of the different treatment approaches, only PP combined with rituximab
      was associated with prolonged remission of proteinuria. CONCLUSIONS: The results
      indicate that patients at high risk for FSGS recurrence can be identified and may
      benefit from carefully planned peritransplant interventions.

PMID- 19384173
TI  - Preemptive management of Epstein-Barr virus reactivation after hematopoietic stem
      cell transplantation.
AB  - BACKGROUND: Epstein-Barr virus (EBV) reactivation after hematopoietic stem-cell
      transplantation can lead to posttransplant lymphoproliferative disease (PTLD),
      which carries a high mortality rate. Among therapeutic and prophylactic options
      being developed, B-cell depletion with monoclonal antibodies is encouraging.
      Because viral load after transplantation is correlated with PTLD occurrence, we
      developed a preemptive attitude based on polymerase chain reaction (PCR)-guided
      rituximab administration. METHODS: We monitored 115 transplant patients with a
      quantitative PCR for EBV DNA performed on whole-blood samples. Criteria for
      treatment initiation were a single PCR above 40,000 DNA genome copies per
      milliliter (gCop/mL) or two rising values above 10,000 gCop/mL. Weekly rituximab
      infusion at the dose of 375 mg/m was administered until negative PCR results were
      available. We evaluated the incidence of EBV reactivation and PTLD development.
      RESULTS: Nineteen patients (16.5%) met the criteria for treatment. Incidence of
      reactivation was the same in high-risk and standard-risk patients (12 vs. 7,
      P=0.38). One patient developed PTLD after discontinuation of therapy due to a
      serious adverse event. No other serious adverse events were noticed. Viral load
      disappeared after a median of three cycles of therapy, and weekly monitoring
      allowed prompt intervention. No PTLD-related death was observed, all-cause
      mortality in the treated population was 68%. CONCLUSIONS: Our PCR-guided and
      rituximab-based preemptive approach to avoid PTLD after allogeneic hematopoietic
      stem-cell transplantation is feasible but probably overtreated patients.
      Prospective trials are strongly needed, they should use uniform PCR techniques
      and consider higher threshold values for treatment initiation.

PMID- 19384174
TI  - ABO incompatible renal transplantation: a paradigm ready for broad
      implementation.
AB  - The requirements for potent immunosuppression coupled with the formidable risk of
      irreversible antibody-mediated rejection (AMR) have thus far limited the
      expansion of ABO incompatible (ABOi) kidney transplantation. We present a
      retrospective review of our single-center experience with 60 consecutive ABOi
      kidney transplants and describe the evolution of our treatment protocol to one
      that consists only of a brief escalation in immunosuppression without long-term B
      cell suppression from splenectomy or anti-CD20. The 1-, 3-, and 5-year graft
      survival rates for the cohort were 98.3%, 92.9%, and 88.7%, respectively, which
      is comparable with United Network for Organ Sharing data for compatible live
      donor transplants. No instances of hyperacute rejection were observed, and no
      grafts were lost secondary to AMR. In fact, fewer than 15% of the patients
      experienced a clinical episode of AMR, and rejections were mild. Elimination of B
      cell ablative therapies did not result in an increased incidence of AMR.
      Excellent graft function persists with a current median creatinine clearance of
      60 mL/min. The findings of this study and the relatively simple therapeutic
      regimen used should facilitate widespread application of ABOi kidney
      transplantation resulting in one of the most rapid escalations in access to
      organs in the modern era of kidney transplantation.

PMID- 19384175
TI  - Marked iron in liver explants in the absence of major hereditary hemochromatosis
      gene defects: a risk factor for cardiac failure.
AB  - BACKGROUND: Patients with hereditary hemochromatosis are known to have an
      increased risk for morbidity and mortality after orthotopic liver
      transplantation. METHODS: The clinical, histological, and genetic findings were
      examined in a series of seven adult patients with marked iron accumulation in
      their liver explants and cardiac failure despite the absence of HFE mutations.
      RESULTS: Causes for cirrhosis were alcohol and hepatitis C virus (HCV) (n=2), HCV
      (n=1), alcohol (n=1), and cryptogenic cirrhosis (n=3). Ages at transplantation
      ranged from 46 to 62 years. Genetic studies confirmed all seven cases were
      negative for HFE mutations C282Y and H63D. The liver explants showed marked iron
      accumulation that predominately involved hepatocytes, with more than 90% of the
      iron in hepatocytes. Two patients required cardiac transplantation and four died
      of cardiac failure. Cardiac tissues obtained from autopsies (n=3), endomyocardial
      biopsy (n=1), or cardiac transplants (n=2) showed marked myocyte hypertrophy and
      iron deposits with or without interstitial fibrosis. CONCLUSIONS: This study
      highlights a unique set of liver transplant patients with marked iron deposition
      in their cirrhotic liver who developed severe cardiac failure and have iron
      deposits in the heart, despite the absence of major HFE gene mutations. The cause
      of the systemic iron overload remains to be discovered.

PMID- 19384176
TI  - Rituximab for humoral rejection after kidney transplantation: an update.

PMID- 19384177
TI  - Structural limitations to the mimetic HLA epitope hypothesis.

PMID- 19384179
TI  - Sirolimus in kidney transplantation indications and practical guidelines: de novo
      sirolimus-based therapy without calcineurin inhibitors.
AB  - A de novo calcineurin inhibitor avoidance regimen based on sirolimus has been
      successfully used worldwide; demonstrating improved renal function from 1 to 5
      years. This includes use of an induction antibody followed by sirolimus,
      mycophenolate mofetil, and steroids. 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, especially the
      first 6 months posttransplant. Experience has also demonstrated that delaying the
      introduction of sirolimus in patients considered at high risk for early mammalian
      target of rapamycin associated complications will optimize these results. For
      such recipients, the initial use of a calcineurin inhibitor drug for 2 to 4
      months is preferred, followed by conversion to sirolimus. The late withdrawal of
      steroids may be possible, but awaits further evaluation in randomized controlled
      trials.

PMID- 19384180
TI  - Sirolimus-based therapy for kidney transplantation from expanded criteria donors.
AB  - The new class of immunosuppressants--inhibitors of the mammalian target of
      rapamycin--has no nephrotoxicity and the capacity to inhibit vascular smooth cell
      proliferation. These characteristics may afford considerable clinical advantages
      in the transplantation of kidneys from expanded criteria donors (ECD). Six
      clinical experiences of the use of sirolimus (SRL) in ECD kidneys recipients have
      been reported in the literature. Although the results varied somewhat, probably
      due to differences in the types of deceased donor and in the immunosuppressive
      regimens used, it seems that a calcineurin inhibitor free, SRL-based protocol can
      assure a good immunosuppressive effect with less nephrotoxicity and a low
      incidence of cytomegalovirus infection. For recipients of ECD kidneys at low
      immunological risk, we would recommend a regimen based on antithymocyte globulin
      induction and SRL, mycophenolate mofetil, and steroids for maintenance. For
      strongly responding recipients, we recommend SRL combined with a reduced, 76% to
      87% dose of calcineurin inhibitor.

PMID- 19384181
TI  - Minimizing the risk of chronic allograft nephropathy.
AB  - Chronic allograft nephropathy, now defined as interstital fibrosis and tubular
      atrophy not otherwise specified, is a near universal finding in transplant kidney
      biopsies by the end of the first decade posttransplantation. After excluding
      death with functioning graft, caused by cardiovascular disease or malignancy,
      chronic allograft nephropathy is the leading cause of graft failure. Original
      assumptions were that this was not a modifiable process but inexorable, likely
      due to past kidney injuries. However, newer understandings suggest that acute or
      subacute processes are involved, and with proper diagnosis, appropriate
      interventions can be instituted. Our method involved a review of the primary and
      secondary prevention trials in calcineurin inhibitor withdrawal. Some of the more
      important causes of progressive graft deterioration include subclinical cellular
      or humoral rejection, and chronic calcineurin inhibitor toxicity. Early graft
      biopsy, assessment of histology, and changes in immunosuppression may be some of
      the most important measures available to protect graft function. The avoidance of
      clinical inertia in pursuing subtle changes in graft function is critical.
      Modification in maintenance immunosuppression may benefit many patients with
      early evidence of graft deterioration.

PMID- 19384182
TI  - Minimizing the risk of posttransplant malignancy.
AB  - Nowadays cancer represents the second main cause of death in renal transplant
      patients with normal function of the graft. The incidence is 10 to 20 times
      higher than normal population. Calcineurin inhibitor therapy contributes to the
      increase in the development of neoplasia. Important evidence could bring a
      preventive effect of mammalian target of rapamycin in skin cancer, Kaposi's
      sarcoma, and renal cell carcinoma.

PMID- 19384183
TI  - Management of side effects of sirolimus therapy.
AB  - Sirolimus (SRL) has been shown to improve long-term graft survival in several
      calcineurin inhibitor avoidance/minimization protocols. Although SRL has been
      suggested to reduce the progression of chronic renal graft damage and to prevent
      the development of neoplasia, two of the most prominent challenges in the field
      of transplantation, its use is significantly limited by an extremely high
      incidence of side effects. Some of the side effects are directly linked to the
      antiproliferative action of SRL, whereas the mechanisms underlying most of the
      undesired effects of the drug are still far from being clarified. Nevertheless,
      there is an increasing body of evidence linking most these drug-associated events
      to SRL dose. In addition, it is now possible to identify well-defined risk
      factors for most of these effects. Thus, to limit SRL-related side effects the
      two golden rules are (1) accurate selection of patients to be treated and (2)
      avoidance of high SRL doses.

PMID- 19384184
TI  - Inhibitors of the mammalian target of rapamycin and transplant tolerance.
AB  - Certainly, achieving and maintaining donor-specific hyporesposiveness is a main
      challenge nowadays in organ transplantation to improve long-term graft survival.
      Immunosuppression seems to be mandatory in the majority of renal transplant
      patients. However, some specific drugs have shown to have interesting
      immunomodulatory effects, regardless of their immunosuppressive activity.
      Sirolimus, an immunosuppressive agent with a distinctive action mechanism has
      shown to be able to directly influence the main two cell subset population in
      charge of controlling alloimmune responses: regulatory T cells and dendritic
      cells. Here, we discuss and analyze the main mechanisms by which sirolimus may
      modulate the alloimmune response, thus facilitating a protolerogenic state in
      renal transplantation.

PMID- 19384185
TI  - Review of symposium. Sirolimus in kidney transplantation.
AB  - Sirolimus (SRL) is a non-nephrotoxic immunosuppressive drug blocking T-cell
      proliferation through mTOR inhibition. SRL can be used as (1) an early drug in a
      calcineurin inhibitor-free protocol in the first 3 months after transplantation,
      (2) in the early and late conversion protocols as suggested by the multicenter
      randomized CONVERT trial, and (3) in recipients from marginal donors, because
      calcineurin inhibitors can increase the preexisting renal damage induced by age,
      hypertension, and diabetes that are frequent in elderly cadaveric donors. In any
      case, SRL should be used in patients with a cutoff of proteinuria (<or=800 mg/24
      hr) or proteinuria-to-creatinine ratio less than 0.11.

PMID- 19384186
TI  - Protocol conversion from a calcineurin inhibitor based therapy to sirolimus.
AB  - Small late-conversion studies found an impressive glomerular filtration rate
      (GFR) increase 1 year after conversion from calcineurin inhibitor (CNI) to
      sirolimus (SRL). This effect could not be detected in the considerably larger
      CONVERT study, which found a lower rate of malignancies in the SRL group. In the
      spare the nephron trial patients converted to SRL exhibited a mean measured GFR
      of 68 mL/min at 1 year compared with 60 mL/min from CNI patients (P<0.05).
      Accordingly, the CONCEPT study which randomized patients to SRL conversion 3
      months after transplantation reported a significant higher GFR in the SRL
      patients at 1 year. These trials showed that conversion of stable renal
      transplant recipients from CNI to SRL is safe.

PMID- 19384187
TI  - IgG4-related sclerosing mastitis: description of a new member of the IgG4-related
      sclerosing diseases.
AB  - Immunoglobulin G (IgG)4-related sclerosing disease is a recently described
      syndrome characterized by mass-forming lesions in various organs due to dense
      lymphoplasmacytic infiltrates and stromal sclerosis, elevated serum IgG4 titer,
      increased tissue IgG4 plasma cells, and favorable clinical outcome. We describe 4
      patients with IgG4-related sclerosing mastitis, which represents a new member of
      this family of diseases. All patients were female with a mean age of 47.5 years,
      presenting with painless masses in 1 or both breasts. One patient had concurrent
      IgG4-related lymphadenopathy, and another had eyelid swelling of undetermined
      cause. The serum IgG4 titer was elevated in 1 tested patient, and circulating
      autoantibodies were found in 3 tested patients. All patients were well with no
      recurrence after excision or biopsy of the mass. Histologically, the breast
      masses featured dense lymphoplasmacytic infiltrates, prominent stromal sclerosis
      and loss of breast lobules. Phlebitis was present in 1 case. IgG4 cells ranged
      from 272 to 495 per high-power field, constituting 49% to 85% of all IgG cells.
      IgG4 cells were scarce in 9 of 9 cases of lymphocytic mastitis and 6 of 7 cases
      of granulomatous mastitis studied as controls. In summary, IgG4-related
      sclerosing mastitis appears to be a distinctive form of mastitis, sometimes
      accompanied by other components of IgG4-related sclerosing disease, and shows a
      favorable clinical outcome.

PMID- 19384188
TI  - The prognostic index: a useful pathologic guide for prediction of nodal
      metastases and survival in penile squamous cell carcinoma.
AB  - A concern of surgical oncologists has been to find a method to select patients
      for groin dissection in penile carcinomas considering the high morbidity of this
      procedure. A promising methodology, in the identification of early metastatic
      foci by the sentinel lymph node technique (initiated in Paraguay in the 1970s),
      was found, using a static anatomic approach, to be associated with a recurrence
      rate of 30%. Later, a dynamic method using radioactive tracers and peritumoral
      dye injection was introduced with an improvement in patients' outcome.
      Recurrences, however, remained high in most studies at a rate of about 15% to 20%
      except in few highly specialized centers with failure rates of 5%. The technical
      sophistication, lack of multicenter reproduction, and cost of dynamic sentinel
      node biopsies preclude their routine implementation in developing countries and
      other approaches are necessary. Because histologic grade, depth of tumor
      infiltration, and perineural invasion (PNI) are considered among the most
      important pathologic prognostic parameters in penile cancer, we devised a
      Prognostic Index combining these 3 factors. In this study, we are evaluating the
      incidence of nodal metastasis according to the Prognostic Index score. Pathologic
      materials from 193 patients with penectomy/circumcision and bilateral groin
      dissections for invasive squamous cell carcinoma were analyzed. The Prognostic
      Index (ranging from 2 to 7) consisted in the addition of numerical values given
      to histologic grade (1 to 3), deepest anatomic level involved by cancer (1 to 3),
      and presence of PNI (0 or 1). Histologic grades were defined as follows: grade 1,
      carcinomas with minimal to no atypias; grade 3, tumors showing any proportion of
      anaplastic cells; and grade 2, the remainder tumors. The anatomic levels and
      their numerical values were: in glans, lamina propria, 1; corpus spongiosum, 2;
      and corpus cavernosum, 3. In foreskin they were: lamina propria, 1; dartos, 2;
      and skin, 3. PNI was evaluated as follows: absence of PNI, 0; presence of PNI, 1.
      Penile intraepithelial neoplasia (carcinoma in situ), or index 1, was excluded
      from the study. Mean follow-up obtained in all patients was of 81 months. The
      distribution of cases and rate of metastasis according to index scores were: 2 (1
      case), no metastasis; 3 (17 cases), no metastasis; 4 (35 cases), 20% of
      metastasis; 5 50 cases), 50% of metastasis; 6 (47 cases), 66% of metastasis; and
      7 (43 cases), 79% of metastasis. On logistic regression analysis evaluating
      various pathologic factors, Prognostic Index scores were found as the best
      predictors of inguinal node metastasis and patients' survival. Inguinal node
      dissections might not be necessary for patients with low indices (2 and 3). Nodal
      dissections might be formally indicated for high-grade indexes (5 to 7). Patients
      with index 4 should be individually assessed for nodal dissection. If sentinel
      node biopsy cannot be performed for various reasons the Prognostic Index might
      represent a useful pathologic guide to the clinicians in the often difficult
      decision to perform an inguinal dissection or not.

PMID- 19384189
TI  - Histologic grade in penile squamous cell carcinoma: visual estimation versus
      digital measurement of proportions of grades, adverse prognosis with any
      proportion of grade 3 and correlation of a Gleason-like system with nodal
      metastasis.
AB  - Histologic grade has been reported as an important pathologic parameter
      predictive of nodal metastases and outcome in patients with penile squamous cell
      carcinoma. There is no consensus about the criteria for grading and the
      proportion of anaplastic cells required to classify a tumor as high grade. The
      incidence and management of heterogeneous tumors (tumors harboring more than 1
      histologic grade) are not well established. The purposes of this study were to
      present a grading model for penile cancer, to test the practicality of the system
      by comparing a visual ("naked-eye") estimation of the proportions of grades with
      a digitally guided measuring system and to determine the influence on nodal
      metastasis of the various proportions of grades. A total of 117 penectomy and
      circumcision specimens with bilateral inguinal lymph node dissections were
      studied and 62 heterogeneous tumors were identified (53%). The following steps
      were taken: (1) design of a grading system model; (2) determination of
      proportions of histologic grades by naked-eye evaluation and by digital
      measurement; (3) evaluation of metastasis according to proportions of grades; (4)
      determination of the influence of site of grade 3 in nodal metastasis; (5) design
      of a Gleason-like scoring system; and (6) statistical evaluation. We designed a 3
      tier grading system. Grade 1: well-differentiated cells, almost undistinguishable
      from normal squamous cells except for the presence of minimal basal/parabasal
      cell atypia. Grade 3: tumors predominantly composed of anaplastic cells. Grade 2:
      all tumors not fitting into criteria described for grade 1 or 3. A visual and
      digital-based (slides scanned and the corresponding areas measured with an image
      editing software) proportions of grades were estimated and the metastatic rate
      between them were confronted using different proportions of grade 3. To evaluate
      the influence of site of grade 3 on nodal metastasis, we selected 20
      heterogeneous tumors. We established 3 sites: superficial, at or within the main
      tumor and deep at front of invasion. There was no significant difference between
      the visual estimation and the digital measurement systems. Heterogeneous tumors
      comprised about half of penile squamous cell carcinomas. The majority of the
      heterogeneous tumors were composed of a combination of grades 2 and 3 (68%). No
      statistical differences were noted in the incidence of nodal metastasis when
      comparing tumors with various proportions of anaplastic cells (P>0.10 in all
      cases). Metastatic rate was significantly more frequent in tumors harboring any
      proportion of grade 3 as compared with tumors without grade 3 (58% vs. 14%,
      P=0.04). Any proportion of grade 3 was equally associated with a significant risk
      of nodal metastasis. A Gleason-like system showed a correlation of higher scores
      and rate of nodal metastasis. No predictive advantage was found when comparing
      the Gleason-like model with the proposed 3-tier grading system. The proposed
      grading system emphasized both ends of the differentiation spectrum and was based
      on easily recognizable morphologic criteria. When histologically evaluating
      penile carcinomas, we recommend a careful search of areas of grade 3. Any focus
      of grade 3 should be sufficient to grade the neoplasm as a high-grade tumor.

PMID- 19384190
TI  - S-100A1 is a reliable marker in distinguishing nephrogenic adenoma from prostatic
      adenocarcinoma.
AB  - Nephrogenic adenoma is a benign lesion that may occur at any site of the
      genitourinary tract, usually in association with previous urothelial injuries.
      Although its pathogenesis is still debated, recent studies seem to confirm its
      derivation from renal tubular epithelium, rather than from a metaplastic process
      of urothelium. In addition to its uncertain origin, there can be diagnostic
      difficulty in distinguishing nephrogenic adenoma from prostatic adenocarcinoma,
      particularly with lesions arising in the prostatic urethra. So far,
      immunohistochemical stains are often needed to make such a distinction, and
      several markers have been proposed, often with controversial results. S100A1 is a
      calcium binding protein that has been recently reported to be expressed in renal
      tubular cells and in a subset of renal cell neoplasms. Alpha-methylacyl-CoA
      racemase (AMACR), a recently identified prostate cancer marker, has also been
      found to be expressed in renal tubules and in some renal epithelial neoplasms. In
      this study, we investigated the expression of S100A1 and AMACR in 18 nephrogenic
      adenomas and in 100 prostatic adenocarcinomas. A strong and distinct cytoplasmic
      or nucleocytoplasmic staining of S100A1 was found in 17 out of 18 cases of
      nephrogenic adenoma (94%), but never in prostatic adenocarcinoma. In contrast,
      AMACR expression was detected in 14 of 18 nephrogenic adenomas (78%) and in 96 of
      100 prostatic adenocarcinomas (96%). We conclude that (1) S100A1 is a specific
      and sensitive immunohistochemical marker to differentiate nephrogenic adenoma
      from prostatic adenocarcinoma; (2) AMACR immunostaining does not seem to be a
      useful marker in distinguishing between these 2 lesions; (3) given that both
      S100A1 and AMACR have been reported to be expressed in renal tubular cells and in
      a subset of renal cell neoplasms, our findings confirm the histogenetic
      relationship between nephrogenic adenoma and renal tubular epithelium.

PMID- 19384191
TI  - Curcumin analogues exhibit enhanced growth suppressive activity in human
      pancreatic cancer cells.
AB  - Curcumin, a yellow pigment and the active component of turmeric, has been shown
      to protect against carcinogenesis and prevent tumor development in several types
      of cancer. However, its low bioavailability and potency prevent it from being
      effective in most chemotherapeutic applications. One potential means of
      circumventing this problem has been the creation of synthetic curcumin analogues.
      We tested the efficacy of two such analogues, known as FLLL11 and FLLL12, in
      human pancreatic cancer cell lines. We compared the impact of curcumin with
      FLLL11 and FLLL12 on cell viability in five different pancreatic cancer cell
      lines. Although all three compounds were capable of lowering viability in all
      cell lines tested, FLLL11 and FLLL12 (IC(50) values between 0.28-3.2 and 0.91
      3.43 micromol/l, respectively) were substantially more potent than curcumin
      (IC(50) values between 8.67 and 20.35 micromol/l). In addition, FLLL11 and FLLL12
      inhibited phosphorylation of signal transducer and activator of transcription 3
      and AKT, two cell signaling pathways frequently found persistently active in many
      forms of cancer. Furthermore, FLLL11 and FLLL12 were found to be more effective
      than curcumin in inducing apoptosis as evidenced by increased cleavage of PARP
      and caspase-3 in pancreatic cancer cell lines. These results indicate that the
      curcumin analogues, FLLL11 and FLLL12, are more effective than curcumin in
      inhibiting cell viability and inducing apoptosis, and may have translational
      potential as chemopreventive or therapeutic agents for pancreatic cancer.

PMID- 19384193
TI  - Head-to-head comparison between bicycle exercise testing and coronary calcium
      score and coronary stenoses on multislice computed tomography.
AB  - OBJECTIVE: To perform a head-to-head comparison between signs of ischemia during
      bicycle exercise testing and coronary atherosclerosis on multislice computed
      tomography (MSCT) in patients with suspected coronary artery disease (CAD).
      METHODS: Two hundred and one patients underwent exercise testing, followed by 64
      slice MSCT. A subgroup of 63 (31%) patients also underwent conventional coronary
      angiography. The exercise test was positive or negative based on
      electrocardiographic signs of ischemia. On MSCT, total calcium score was
      obtained. Based on MSCT angiography, the patients were classified as having
      normal MSCT or coronary atherosclerosis [with nonobstructive and obstructive CAD
      (>/=50% luminal narrowing) present]. RESULTS: In 178 patients with interpretable
      examinations, the exercise test was positive in 36 (20%) and negative in 142
      (80%) patients. Calcium score was identical in patients with a positive [median
      (interquartile range) 11 (0-343)] and a negative exercise test [18 (0-335),
      P=NS]. The prevalence of nonobstructive CAD was the same in two patients groups
      [13 (36%) patients with a positive vs. 54 (38%) patients with a negative exercise
      test, P=NS]. Although obstructive CAD was observed in 15 (42%) patients having a
      positive exercise test, obstructive lesions were also present in 38 (27%)
      patients without ischemia on exercise testing. The findings were confirmed by
      conventional coronary angiography. CONCLUSION: No correlation was observed
      between ischemia on exercise testing and both calcium scoring and nonobstructive
      CAD on MSCT. A large proportion of obstructive lesions on MSCT were not observed
      on exercise testing. Potentially, MSCT may provide additional information on CAD.

PMID- 19384194
TI  - The effect of implementing high-intensity intensive care unit staffing model on
      outcome of critically ill oncology patients.
AB  - OBJECTIVE: Implementing high-intensity staffing model improves outcome in general
      intensive care units (ICUs). We studied the effect of implementing such a model
      on the outcome of critically ill medical patients in an oncology ICU. DESIGN: We
      compared admission rates, ICU mortality rates (MRs), 28-day MRs, length of stay
      (LOS) for patients discharged alive, and bed turnover rates of medical patients
      admitted to the ICU in the year 2004 (before an intensivist model was
      established) with those in the years 2006 and 2007 (after the model was
      established). We allowed for 1 year of transition to implement the changes
      required including the transformation of the ICU to a closed ICU with daily
      multidisciplinary rounds led by an intensivist as described in the Leapfrog
      model. RESULTS: ICU admissions increased from 236 patients (2004) to 388 (2006)
      and 446 (2007). There was no significant difference in the disease severity of
      illness when compared by Acute Physiology and Chronic Health Evaluation II
      scores, 20.6 (before) vs. 20.9 (after) (p = 0.386). ICU MR for the consecutive
      years decreased from 35.17% (95% confidence interval [CI]: 29.08-41.26) to 23.97%
      (95% CI: 19.72-28.22) and 22.87% (95% CI: 18.97-26.77), and 28-day MRs decreased
      from 47.69% (95% CI: 40.68-54.7) to 38.24% (95% CI: 32.91-43.58) and 29.84% (95%
      CI: 24.79-34.89). LOS (for patients who survived) decreased from a mean of 4.26
      days (95% CI: 3.19-5.33) to 2.63 (95% CI: 2.4-2.86) and 2.63 (95% CI: 2.4-2.86).
      Bed turnover rates increased from 5.0 patient/bed (95% CI: 4.22-5.78) to 6.9
      patient/bed (95% CI: 6.04-7.77) and 7.56 patient/bed (95% CI: 6.67-8.44).
      CONCLUSION: Implementing a high-intensity staffing model is associated with
      significant improvements in MRs, LOS, and bed utilization of critically ill
      oncology patients.

PMID- 19384192
TI  - Effects of force-titrated valsartan/hydrochlorothiazide versus
      amlodipine/hydrochlorothiazide on ambulatory blood pressure in patients with
      stage 2 hypertension: the EVALUATE study.
AB  - BACKGROUND: Previous studies using the combination of angiotensin-receptor
      blockers and hydrochlorothiazide (HCTZ) have shown superior ambulatory blood
      pressure (ABP) reduction in study participants with stage 2 hypertension compared
      with monotherapy. OBJECTIVE: This multicenter, double-blind, parallel group,
      forced-titration study of individuals with stage 2 hypertension, compared the
      efficacy of valsartan and amlodipine in combination with HCTZ on ABP reduction.
      METHODS: After a 2-week washout period, participants (n=482) with mean office
      sitting systolic BP >or=160 mmHg and <or=200 mmHg were randomized to receive
      treatment with either valsartan 160 mg (n=241) or amlodipine 5 mg (n=241), force
      titrated to a maximum dose of valsartan/HCTZ 320/25 mg or amlodipine/HCTZ 10/25
      mg over 6 weeks and continued through week 10. The primary endpoint was change in
      mean 24-h ambulatory systolic BP from baseline to week 10. RESULTS: At week 10,
      changes from baseline in mean office BP were significantly (P<0.0001) decreased
      by both valsartan/HCTZ (-34.2/-14.2 mmHg) and amlodipine/HCTZ (-34.1/-14.7 mmHg).
      Changes from baseline in mean 24-h ABP were significantly (P<0.0001) decreased by
      both valsartan/HCTZ (-21.1/-12.5 mmHg) and amlodipine/HCTZ (-18.1/-9.9 mmHg).
      However, treatment with valsartan/HCTZ provided significant additional systolic
      BP (-3.8 mmHg; P=0.0042) and diastolic BP (-2.7 mmHg; P=0.0002) reduction
      compared with the amlodipine/HCTZ group. The proportion of individuals reaching
      the office goal BP (<140/80 mmHg) were similar in the valsartan/HCTZ (55.3%)
      versus amlodipine/HCTZ (54.9%) group, ABP control rates for the recommended ABP
      goal (<130/80 mmHg) were greater (P=0.0170) in the valsartan/HCTZ group (54.3%)
      than the amlodipine/HCTZ group (42.7%). Both treatments were well tolerated.
      CONCLUSION: On the basis of ABP monitoring but not office measurements, the fixed
      dose combination of valsartan/HCTZ is a significantly more effective treatment
      regimen than amlodipine/HCTZ, with similar tolerability.

PMID- 19384195
TI  - Increased long-term mortality among survivors of acute carbon monoxide poisoning.
AB  - OBJECTIVE: Recent data suggest that patients surviving acute carbon monoxide (CO)
      poisoning (COP) may have increased risk for long-term mortality. The objective of
      this study was to analyze long-term mortality of a large population of CO
      poisoned patients treated at one medical center over three decades. DESIGN:
      Retrospective cohort study of patients treated with hyperbaric oxygen and
      surviving the acute poisoning episode. Long-term mortality was compared to a
      standard population. Comparison of mortality within the cohort by clinical
      indicators of poisoning severity was assessed using Cox proportional hazards
      regression analysis. SETTING: Regional referral center for hyperbaric treatment
      of COP. PATIENTS: One thousand seventy-three patients aged >or=18 years treated
      from 1978 to 2005. INTERVENTIONS: All patients received hyperbaric oxygen
      treatment. MEASUREMENTS AND MAIN RESULTS: During 11,741 person-years of follow
      up, 162 subjects died. The expected number of deaths was 87 (standardized
      mortality ratio [SMR]), 1.9; 95% confidence interval [CI], 1.6-2.2). Most of the
      excess mortality was in the group treated initially for intentional COP (58
      excess deaths; SMR, 3.7; 95% CI, 2.9-4.6) vs. those treated for accidental COP
      (17 excess deaths; SMR, 1.3; 95% CI, 1.01-1.6). For the entire cohort, the major
      causes of death with significantly raised mortality were mental and psychiatric
      disorders, injuries, and violence. More specific causes of death with
      significantly raised mortality were alcoholism, motor vehicle accidents with
      pedestrians, motor vehicle accidents of unspecified type, accidental poisonings,
      and intentional self-harm. Within cohort comparisons showed that no difference in
      survival was observed by measure of CO poisoning severity, after controlling for
      age at poisoning, sex, race, and intent of CO poisoning. CONCLUSIONS: Adult
      survivors of acute CO poisoning treated with hyperbaric oxygen were at increased
      risk for long-term mortality. Such patients should be followed closely after
      discharge with consideration given to psychiatric and/or neurocognitive
      evaluation, as appropriate.

PMID- 19384196
TI  - Detrimental hemodynamic and inflammatory effects of microparticles originating
      from septic rats.
AB  - OBJECTIVE: Microparticles (MPs) are membrane vesicles with procoagulant and
      proinflammatory properties released during cell activation and might be
      potentially involved in the pathophysiology of septic shock. This study was
      designed to assess the effects of MPs from septic origin on the systemic
      hemodynamics as well as on the inflammatory, oxidative, and nitrosative stresses.
      DESIGN: A prospective, randomized, controlled experimental study with repeated
      measurements. SETTING: Investigational animal laboratory. SUBJECTS: Forty healthy
      rats were randomly allocated to three groups: 10 animals inoculated with MPs
      isolated from control rats (cMPs), 15 animals inoculated with MPs isolated from
      sham rats (shMPs), and 15 animals inoculated with MPs isolated from rats with
      peritonitis (sMPs). INTERVENTIONS: Rats were anesthetized, mechanically
      ventilated, and infused with the same amount of cMPs, shMPs, or sMPs. We measured
      the heart rate, mean arterial pressure, carotid artery, and portal vein blood
      flows. Hemodynamic parameters were recorded during 7 hours, and then animals were
      killed. Aorta and heart were harvested for further in vitro tissue analyses.
      MEASUREMENTS AND MAIN RESULTS: 1) The cellular origin (phenotype) but not the
      circulating concentration of MPs was different in septic rats, characterized by a
      significant increase in leukocyte-derived MPs. 2) sMPs but not cMPs or shMPs
      decreased mean arterial pressure without any effect on carotid artery and portal
      vein blood flows. 3) Rats inoculated with sMPs exhibited an increase in
      superoxide ion production and nuclear factor kappa B activity, overexpression of
      inducible nitric oxide synthase with subsequent nitric oxide overproduction and
      decrease in endothelial nitric oxide synthase activation. CONCLUSIONS: Rats with
      sepsis induced by peritonitis exhibited a specific phenotype of MPs. Inoculation
      of sMPs in healthy rats reproduced hemodynamic, septic inflammatory patterns,
      associated with oxidative and nitrosative stresses.

PMID- 19384197
TI  - Continuous electroencephalography in the medical intensive care unit.
AB  - OBJECTIVES: To examine predictors and the prognostic value of electrographic
      seizures (ESZs) and periodic epileptiform discharges (PEDs) in medical intensive
      care unit (MICU) patients without a primary acute neurologic condition. DESIGN:
      Retrospective study. SETTING: MICU in a university hospital. PATIENTS: A total of
      201 consecutive patients admitted to the MICU between July 2004 and January 2007
      without known acute neurologic injury and who underwent continuous
      electroencephalography monitoring (cEEG) for investigation of possible seizures
      or changes in mental status. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS:
      Median time from intensive care unit (ICU) admission to cEEG was 1 day
      (interquartile range 1-4). The majority of patients (60%) had sepsis as the
      primary admission diagnosis and 48% were comatose at the time of cEEG. Ten
      percent (n = 21) of patients had ESZs, 17% (n = 34) had PEDs, 5% (n = 10) had
      both, and 22% (n = 45) had either ESZs or PEDs. Seizures during cEEG were purely
      electrographic (no detectable clinical correlate) in the majority (67%) of
      patients. Patients with sepsis had a higher rate of ESZs or PEDs than those
      without sepsis (32% vs. 9%, p < 0.001). On multivariable analysis, sepsis at ICU
      admission was the only significant predictor of ESZs or PEDs (odds ratio 4.6, 95%
      confidence interval 1.9-12.7, p = 0.002). After controlling for age, coma, and
      organ dysfunction, the presence of ESZs or PEDs was associated with death or
      severe disability at hospital discharge (89% with ESZs or PEDs, vs. 39% if not;
      odds ratio 19.1, 95% confidence interval 6.3-74.6, p < 0.001). CONCLUSION: In
      this retrospective study of MICU patients monitored with cEEG, ESZs and PEDs were
      frequent, predominantly in patients with sepsis. Seizures were mainly
      nonconvulsive. Both seizures and periodic discharges were associated with poor
      outcome. Prospective studies are warranted to determine more precisely the
      frequency and clinical impact of nonconvulsive seizures and periodic discharges,
      particularly in septic patients.

PMID- 19384198
TI  - Glutamine attenuates tubular cell apoptosis in acute kidney injury via inhibition
      of the c-Jun N-terminal kinase phosphorylation of 14-3-3.
AB  - OBJECTIVE: Tubular cell apoptosis is linked to the development of acute kidney
      injury (AKI), which is a frequent complication of traumatic rhabdomyolysis. The
      14-3-3 protein, a multifunctional regulatory protein, binds a variety of
      apoptotic proteins and is a target of c-Jun N-terminal kinase (JNK) in the cell
      death signaling pathway. Therefore, we examined whether JNK phosphorylates 14-3-3
      and downstream mitochondrial death pathway mediates apoptosis in myoglobinuric
      acute kidney injury to determine whether these events are regulated by glutamine,
      which is known to induce heat shock protein 70 (Hsp70), or involved in the
      synthesis of glutathione (GSH). DESIGN: A prospective, randomized, controlled
      animal trial. SETTING: University research laboratory. SUBJECTS: Male Sprague
      Dawley rats. INTERVENTIONS: We utilized a rat model of myoglobinuric AKI.
      Glutamine or saline was administered intraperitoneally before and after glycerol
      injection. Apoptotic cell death was determined via transferase-mediated
      deoxyuridine triphosphate nick-end labeling staining, and Hsp70, JNK, phospho
      JNK, 14-3-3, phospho-14-3-3, and many other apoptotic proteins were examined via
      Western blot. Relative interactions between these proteins were tested by
      coimmunoprecipitation analyses. Also, GSH levels were determined to further test
      whether glutamine affects apoptotic cell death in myoglobinuric AKI. MEASUREMENTS
      AND MAIN RESULTS: Glutamine treatment elevated levels of Hsp70 or reduced GSH and
      attenuated tubular cell apoptosis in kidney tissues of rats with myoglobinuric
      AKI. Further, Hsp70 physically associated with JNK, thereby limiting its
      activation. In addition, JNK evidently interacted with 14-3-3, leading to its
      phosphorylation, Bad or Bax dissociation from 14-3-3, and subsequent Bax
      mitochondrial translocation and caspase activation in rats with acute renal
      failure. Glutamine treatment very modestly lowered elevated levels of serum
      creatinine in AKI rats. CONCLUSIONS: A signaling link between JNK and 14-3-3 and
      subsequent mitochondrial death pathway may partly act as an early signaling that
      promotes apoptotic cell death leading to AKI, and glutamine may at least
      partially prevent apoptosis via enhancing Hsp70 or GSH levels.

PMID- 19384199
TI  - Glutaraldehyde-polymerized bovine hemoglobin and phosphodiesterase-5 inhibition.
AB  - OBJECTIVE: Hemoglobin-based oxygen carriers (HBOC) of several types scavenge
      nitric oxide from the vasculature resulting in vasoconstriction and hypertension,
      both systemic and pulmonary. Phosphodiesterase-5 (PDE5) inhibitors promote nitric
      oxide activity and enhance vasodilation. The purpose of this study was to
      determine whether combined therapy of glutaraldehyde-polymerized bovine
      hemoglobin (HBOC) with a PDE5 inhibitor would counter the negative hemodynamic
      consequences of HBOC therapy alone, resulting in improved hemodynamics and oxygen
      delivery. DESIGN: A controlled, experimental study. SETTING: A research
      laboratory at a university. SUBJECTS: Conscious male Sprague-Dawley rats.
      INTERVENTIONS: Glutaraldehyde-polymerized bovine hemoglobin (HBOC), sildenafil
      (PDE5 inhibitor), and lactated Ringer's solution (control). MEASUREMENTS AND MAIN
      RESULTS: Infusion of the HBOC resulted in significant (p < 0.05) systemic and
      pulmonary vasoconstriction, with reduced cardiac output and reduced oxygen
      delivery to the periphery. Infusion of lactated Ringer's demonstrated no changes
      in the measured variables. Infusion of sildenafil alone reduced systemic and
      pulmonary artery blood pressure, while maintaining cardiac output and oxygen
      delivery. Combined HBOC and sildenafil infusion resulted in stable systemic blood
      pressure, cardiac output, and oxygen delivery. However, the addition of
      sildenafil to HBOC did not fully ameliorate the pulmonary vasoconstriction caused
      by HBOC. CONCLUSION: The HBOC used in this study resulted in pulmonary and
      systemic hypertension, reduced cardiac output, and oxygen delivery. These
      negative consequences of HBOC treatment can be largely overcome by combing HBOC
      treatment with a PDE5 inhibitor (sildenafil). Thus, these data support the
      continued investigation of combined HBOC and PDE5 inhibitor treatment in
      circumstances in which HBOC therapy is being considered.

PMID- 19384200
TI  - Experiencing the pediatric intensive care unit: perspective from parents of
      children with severe antecedent disabilities.
AB  - OBJECTIVE: To describe the experience of pediatric intensive care hospitalization
      from the perspective of a parents of children with severe, antecedent disability.
      DESIGN: Qualitative analysis of data obtained through semistructured interviews.
      SETTING: Pediatric intensive care unit (PICU) in a children's hospital. SUBJECTS:
      Parents of eight children admitted to the PICU with severe antecedent
      disabilities. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were
      collected between May and July 2006. Parents were interviewed during, or just
      after, PICU admission until data saturation was achieved. Seven major themes
      emerged from analysis: 1) know my child's baseline; 2) integrate and bridge
      multiple services; 3) disconnect between role of parent at home versus parent in
      the PICU; 4) a PICU admission does not equate with respite; 5) high stakes
      learning environment; 6) heterogeneity within group; and 7) lack of fit within
      the acute care model. The need for stellar communication and mutuality within the
      parent-professional relationship were common conceptual threads through all
      interviews. CONCLUSIONS: Children with severe antecedent disabilities and their
      parents are inextricably linked with critical care services. Study results
      provide data that can be used to help clinicians better understand the
      perspectives of these parents and also help guide interventions to improve care
      and support. Although communication is essential, the structure and processes of
      critical care including rounding format, continuity in management, and mutual
      participation models should be tested and tailored to better meet parental needs
      and expectations.

PMID- 19384201
TI  - A systematic review on clinical benefits of continuous administration of beta
      lactam antibiotics.
AB  - OBJECTIVE: The clinical benefits of extended infusion or continuous infusion of
      beta-lactam antibiotics remain controversial. We systematically reviewed the
      literature to determine whether any clinical benefits exist for administration of
      beta-lactam antibiotics by extended or continuous infusion. DATA SOURCE: PubMed
      (January 1950 to November 2007), EMBASE (1966 to November 2007), and the Cochrane
      Controlled Trial Register were searched (updated November 2007). STUDY
      SELECTIONS: Randomized controlled trials (RCTs) were meta-analyzed, and
      observational studies were described by two unblinded reviewers. DATA EXTRACTION:
      A total of 846 patients from eligible prospective randomized controlled studies
      were included in the meta-analysis. Two observational studies were deemed
      appropriate for description. DATA SYNTHESIS: A meta-analysis of prospective RCTs
      was undertaken using Review Manager. Among a total of 59 potentially relevant
      studies, 14 RCTs involving a total of 846 patients from nine countries were
      deemed appropriate for meta-analysis. The use of continuous infusion of a beta
      lactam antibiotic was not associated with an improvement in clinical cure (n =
      755 patients; odds ratio: 1.04, 95% confidence interval: 0.74-1.46, p = 0.83, I =
      0%) or mortality (n = 541 patients; odds ratio: 1.00, 95% confidence interval:
      0.48-2.06, p = 1.00, I = 14.8%). All RCTs except one used a higher antibiotic
      dose in the bolus administration group. Two observational studies, not pooled
      because they did not meet the a priori criteria for meta-analysis, showed that
      beta-lactam administration by extended or continuous infusion was associated with
      an improvement in clinical cure. The difference in the results between the meta
      analysis results and the observational studies could be explained by the bias
      created by a higher dose of antibiotic in the bolus group in the RCTs and because
      many of the RCTs only recruited patients with a low acuity of illness.
      CONCLUSIONS: The limited data available suggest that continuous infusion of beta
      lactam antibiotics leads to the same clinical results as higher dosed bolus
      administration in hospitalized patients.

PMID- 19384202
TI  - Low-volume resuscitation from traumatic hemorrhagic shock with Na+/H+ exchanger
      inhibitor.
AB  - OBJECTIVE: To evaluate the use of a Na/H exchanger (NHE-1) inhibitor as a
      cardioprotective adjunct therapy to low-volume resuscitation in two different rat
      models of traumatic hemorrhagic shock. DESIGN: Experimental, prospective study.
      SETTING: Medical center research laboratory. SUBJECTS: Sprague Dawley male rats.
      INTERVENTIONS: Series 1: femur fracture was induced in anesthetized rats,
      followed by pressure-controlled hemorrhage (40 mm Hg for 20 minutes) and
      resuscitation. Groups: 1) no therapy; 2) 15 mL/kg hetastarch; and 3) 3 mg/kg
      benzamide, N-(aminoiminomethyl)-4-[4-(2-furanylcarbonyl)-1-piperazinyl]-3
      (methylsulfonyl), methanesulfonate (BIIB513) (NHE-1 inhibitor) + 15 mL/kg
      hetastarch infusion over 40 minutes. The experiment was terminated at 6 hours
      after resuscitation. Series 2: the rats received laparotomy and closure under
      anesthesia and subsequently remained conscious for the rest of the study. The
      rats were subjected to volume-controlled hemorrhage (2.5 mL/100 g) followed by
      resuscitation as described in series 1. The experiment was terminated at 24 hours
      after resuscitation. MEASUREMENTS AND MAIN RESULTS: Series 1: all animals in the
      no-therapy group died within 2 hours. Compared with hetastarch infusion alone,
      the addition of NHE-1 inhibitor improved the hemodynamic response to fluid
      resuscitation, increased blood oxygen content, prevented metabolic acidosis, and
      improved 6-hour survival (42% in hetastarch group vs. 80% in BIIB513 + hetastarch
      group). NHE-1 inhibition also resulted in reduced plasma levels of tumor necrosis
      factor-alpha, intercellular adhesion molecule-1, and C-reactive protein, and
      attenuated neutrophil infiltration in the liver. Series 2: all animals in the no
      therapy group died within 4 hours after hemorrhage. Compared with hetastarch
      infusion alone, the addition of BIIB513 improved 24-hour survival (44% in
      hetastarch group vs. 78% in BIIB513 + hetastarch group). NHE-1 inhibition also
      reduced plasma levels alanine aminotransferase at 24 hours after resuscitation.
      CONCLUSIONS: NHE-1 inhibition facilitated the hemodynamic response to fluid
      resuscitation, attenuated tissue inflammatory injury, and organ dysfunction, but
      most importantly improved survival.

PMID- 19384203
TI  - Effects of hydroxyethyl starch resuscitation on extravascular lung water and
      pulmonary permeability in sepsis-related acute respiratory distress syndrome.
AB  - OBJECTIVE: Hydroxyethyl starch (HES) has greater volume expansion effect and
      longer intravascular persistence than crystalloids. HES also decreases
      microvascular permeability and capillary leakage by biophysically plugging
      endothelial leaks, exerting an anti-inflammatory effect, and decreasing
      activation of endothelial cells. The aim of our study was to determine whether
      medium molecular weight HES (pentastarch) resuscitation in the early stage of
      acute respiratory distress syndrome (ARDS) simultaneously increases cardiac
      output without worsening pulmonary edema and whether it attenuates pulmonary
      vascular permeability. DESIGN: Prospective observational study. SETTING: Twenty
      bed medical intensive care unit of a tertiary medical center. PATIENTS: Twenty
      patients with early-stage ARDS. INTERVENTION: Volume expansion with a 500-mL
      infusion of 10% pentastarch (HES 200/0.5) at a rate of 10 mL/kg/hr. MEASUREMENTS
      AND MAIN RESULTS: Baseline hemodynamics including systemic and pulmonary artery
      blood pressures, central venous pressure, pulmonary artery occlusion pressure,
      and cardiac output were obtained from an online HP Component Monitoring System
      and a pulmonary artery catheter. Intrathoracic blood volume (ITBV), global end
      diastolic volume, extravascular lung water (EVLW), and pulmonary vascular
      permeability (EVLW/ITBV) were measured with a PiCCOplus monitor. Hemodynamic
      measurements were repeated immediately and 2, 4, and 6 hours after volume
      expansion. Pentastarch loading significantly increased central venous pressure,
      pulmonary artery occlusion pressure, pulmonary arterial pressures, and cardiac
      output. Pulmonary mechanics, venous admixtures, and EVLW values remained
      unchanged throughout the study. EVLW/ITBV significantly decreased immediately
      after the pentastarch infusion. CONCLUSIONS: In patients with early ARDS,
      pentastarch resuscitation significantly improved their hemodynamics and cardiac
      output without worsening pulmonary edema and pulmonary mechanics. It even
      attenuated pulmonary vascular permeability.

PMID- 19384204
TI  - Red blood cell transfusion practices in acute lung injury: what do patient
      factors contribute?
AB  - OBJECTIVE: To describe red blood cell (RBC) transfusion practices and evaluate
      the association between patient-related factors and pretransfusion hemoglobin
      concentration in acute lung injury (ALI). DESIGN: Secondary analysis of
      prospectively collected data. SETTING: Nine intensive care units (ICUs) in three
      teaching hospitals in Baltimore, MD. PATIENTS: Two hundred forty-nine consecutive
      patients with ALI requiring mechanical ventilation. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Simple and multiple linear regression analyses
      were used to evaluate the association between the nadir hemoglobin concentration
      on the day of initial RBC transfusion and 20 patient-level demographic, clinical
      and ICU treatment factors as well as ICU type. Of 249 patients with ALI, 47%
      received an RBC transfusion in the ICU without evidence of active hemorrhage or
      acute cardiac ischemia. The mean (sd) nadir hemoglobin on the day of first
      transfusion was 7.7 (1.1) g/dL with 67%, 36%, 15%, and 5% of patients transfused
      at >7, >8, >9, and >10 g/dL, respectively. Transfused patients received a mean
      (sd) of 5 (6) RBC units from ALI diagnosis to ICU discharge. Prehospital use of
      iron or erythropoietin and platelet transfusion in the ICU were independently
      associated with lower pretransfusion hemoglobin concentrations. No patient
      factors were associated with higher hemoglobin concentrations. Admission to a
      surgical (vs. medical) ICU was independently associated with a 0.6 g/dL (95%
      confidence interval 0.1-1.1 g/dL) higher pretransfusion hemoglobin. CONCLUSIONS:
      Patients with ALI commonly receive RBC transfusions in the ICU. The
      pretransfusion hemoglobin observed in our study was lower than earlier studies,
      but a restrictive strategy was not universally adopted. Patient factors do not
      explain the gap between clinical trial evidence and routine transfusion
      practices. Future studies should further explore ICU- and physician-related
      factors as a source of variability in transfusion practice.

PMID- 19384205
TI  - Monocyte activation by necrotic cells is promoted by mitochondrial proteins and
      formyl peptide receptors.
AB  - OBJECTIVE: Necrotic cells evoke potent innate immune responses through unclear
      mechanisms. The mitochondrial fraction of the cell retains constituents of its
      bacterial ancestors, including N-formyl peptides, which are potentially
      immunogenic. Thus, we hypothesized that the mitochondrial fraction of the cell,
      particularly N-formyl peptides, contributes significantly to the activation of
      monocytes by necrotic cells. DESIGN: Human peripheral blood monocytes were
      incubated with necrotic cell fractions and mitochondrial proteins to investigate
      their potential for immune cell activation. SETTING: University Medical Center
      Research Laboratory. SUBJECTS: Healthy human adults served as blood donors.
      MEASUREMENTS AND MAIN RESULTS: Human blood monocyte activation was measured after
      treatment with cytosolic, nuclear and mitochondrial fractions of necrotic HepG2
      cells or necrotic HepG2 cells depleted of N-formyl peptides [Rho(0) cells]. The
      specific role of the high affinity formyl peptide receptor (FPR) was then tested
      using specific pharmacologic inhibitors and RNA silencing. The capacity of
      mitochondrial N-formyl peptides to activate monocytes was confirmed using a
      synthetic peptide conforming to the N-terminus of mitochondrial nicotinamide
      adenine dinucleotide subunit 6. The results demonstrated that mitochondrial cell
      fractions most potently activated monocytes, and interleukin (IL)-8 was
      selectively released at low-protein concentrations. Mitochondria from Rho(0)
      cells induced minimal monocyte IL-8 release, and specific pharmacologic
      inhibitors and RNA-silencing confirmed that FPR contributes significantly to
      monocyte IL-8 responses to both necrotic cells and mitochondrial proteins. N
      formyl peptides alone did not induce monocyte IL-8 release; whereas, the
      combination of mitochondrial N-formyl peptides and mitochondrial transcription
      factor A (TFAM) dramatically increased IL-8 release from monocytes. Likewise,
      high mobility group box 1, the nuclear homolog of TFAM, did not induce monocyte
      IL-8 release unless combined with mitochondrial N-formyl peptides. CONCLUSIONS:
      Interactions between mitochondrial N-formyl peptides and FPR in the presence of
      other mitochondrial antigens (e.g., TFAM) contributes significantly to the
      activation of monocytes by necrotic cells.

PMID- 19384206
TI  - Comparison of delirium assessment tools in a mixed intensive care unit.
AB  - OBJECTIVE: Delirium is a frequent problem in the intensive care unit (ICU)
      associated with poor prognosis. Delirium in the ICU is underdiagnosed by nursing
      and medical staff. Several detection methods have been developed for use in ICU
      patients. The aim of this study was to compare the value of three detection
      methods (the Confusion Assessment Method for the ICU [CAM-ICU], the Intensive
      Care Delirium Screening Checklist [ICDSC] and the impression of the ICU physician
      with the diagnosis of a psychiatrist, neurologist, or geriatrician). DESIGN:
      Prospective study. SETTING AND PATIENTS: During an 8-month period, 126 patients
      (mean age 62.4 years, sd 15.0; mean Acute Physiology and Chronic Health
      Evaluation II score 20.9, sd 7.5) admitted to a 32-bed mixed medical and surgical
      ICU were studied. MEASUREMENTS: The included patients were assessed independently
      by trained ICU nurses using either the CAM-ICU or the ICDSC. Furthermore, the ICU
      physician was asked whether a patient was delirious or not. A psychiatrist,
      geriatrician, or neurologist serving as reference rater diagnosed delirium using
      established criteria. MAIN RESULTS: The CAM-ICU showed superior sensitivity and
      negative predictive value (64% and 83%) compared with the ICDSC (43% and 75%).
      The ICDSC showed higher specificity and positive predictive value (95% and 82%
      vs. 88% and 72%). The sensitivity of the physicians view was only 29%.
      CONCLUSIONS: ICU physicians underdiagnose delirium in the ICU, which underlines
      the necessity of standard evaluation in all critically ill patients. In our mixed
      ICU population, the CAM-ICU had a higher sensitivity than the ICDSC.

PMID- 19384207
TI  - Time course of anemia during six months follow up following intensive care
      discharge and factors associated with impaired recovery of erythropoiesis.
AB  - OBJECTIVES: Anemia is a common complication of critical illness, but its duration
      after intensive care discharge and possible contributory factors have not been
      studied. Our aim was to follow patients discharged anemic from the intensive care
      unit (ICU) for up to 6 months and determine the duration of and possible reasons
      for persisting anemia. DESIGN: Prospective observational cohort study of
      intensive care (ICU) survivors with moderate-severe anemia at the time of ICU
      discharge. Erythropoietic and inflammatory markers were measured at regular
      intervals over six months to assess red cell production and factors limiting
      recovery from anemia. SETTING: An 18-bed medico-surgical ICU in a Scottish
      university teaching hospital. PATIENTS: Patients who required >24 hrs of
      ventilatory support and were discharged from intensive care with hemoglobin < 100
      g/L were studied prospectively over 6 months. 30 patients were recruited; 19
      completed 6 months follow-up, 6 died during the study period, and 5 completed
      part of the follow up. Patients with ongoing renal failure or chronic hematologic
      disorders were excluded. MEASUREMENTS AND MAIN RESULTS: 47% (9 of 19) of patients
      completing 6 months follow up recovered from their anemia. The median time to
      recovery was 11 wks (1, 3 quartiles: 9, 26 wks). 10 patients (53%) were still
      anemic 6 months after ICU discharge. No patients developed iron, vitamin B12 or
      folate deficiency. An inappropriately low erythropoietin response to anemia was
      observed in virtually all patients and did not distinguish nonrecovering
      patients. Patients with delayed recovery or persisting anemia during the 13 wks
      following ICU discharge had higher levels of circulating inflammatory markers (IL
      6 and C-reactive protein) and did not exhibit reticulocytosis during the weeks
      following discharge. CONCLUSIONS: Anemia persists in many patients following
      critical illness and is associated with ongoing inflammation, inappropriate
      erythropoietin response and poor marrow red cell production.

PMID- 19384208
TI  - Metabolic benefits of surface counter warming during therapeutic temperature
      modulation.
AB  - OBJECTIVE: To determine the impact of counter warming (CW) with an air
      circulating blanket on shivering and metabolic profile during therapeutic
      temperature modulation (TTM). DESIGN: A prospective observational study. SETTING:
      An 18-bed neurologic intensive care unit. PATIENTS: Fifty mechanically ventilated
      patients with brain injury undergoing TTM with automated surface and
      intravascular devices. INTERVENTIONS: Fifty indirect calorimetry (IDC)
      measurements with and without CW during TTM. MEASUREMENTS AND MAIN RESULTS: IDC
      was continuously performed for 10-15 minutes at baseline with CW (phase I), off
      CW (phase II), and again after the return of CW (phase III). Shivering severity
      during each phase was scored on a scale of 0-3 using the Bedside Shivering
      Assessment Scale (BSAS). Resting energy expenditure (REE), oxygen consumption,
      and carbon dioxide production were determined by IDC; 56% were women, with mean
      age 61 +/- 15 years. At the time of IDC, 72% of patients had signs of shivering
      (BSAS >0). All measures of basal metabolism increased after removal of the air
      warming blanket (from phases I and II); REE increased by 27% and oxygen
      consumption by 29% (both p < 0.002). A one-point increase in baseline BSAS was
      noted in 55% (n = 23/42) of patients from phase I to phase II. In a multivariate
      analysis, sedative use (p = 0.03), baseline moderate to severe shivering (p =
      0.04), and lower serum magnesium levels (p = 0.01) were associated with greater
      increases in REE between phase I and phase II of CW. Phase III of CW was
      associated with a reversal in the increases in all metabolic variables.
      CONCLUSIONS: Surface CW provides beneficial control of shivering and improves the
      metabolic profile during TTM.

PMID- 19384209
TI  - Helmet with specific settings versus facemask for noninvasive ventilation.
AB  - OBJECTIVE: To compare the physiologic effects of noninvasive pressure-support
      ventilation (NPSV) delivered by a facemask, a helmet with the same settings, and
      a helmet with specific settings. Inspiratory muscle effort, gas exchange, patient
      ventilator synchrony, and comfort were evaluated. DESIGN: Prospective crossover
      study. SETTING: A 13-bed medical intensive care unit in a university hospital.
      PATIENTS: Eleven patients at risk for respiratory distress requiring early NPSV
      after extubation. INTERVENTION: One hour after extubation, three 20-minute NPSV
      periods were delivered in a random order by facemask, helmet, and helmet with 50%
      increases in both pressure support and positive end-expiratory pressure and with
      the highest pressurization rate (95% max). MEASUREMENTS AND MAIN RESULTS: Flow
      and airway, esophageal, and gastric pressure signals were measured under the
      three NPSV conditions and during spontaneous breathing. Compared with the
      facemask, the helmet with the same settings resulted in a greater inspiratory
      muscle effort, but this difference was abolished by the specific settings
      (pressure-time product in cm H2O.s.min, 63.8 [27.3-85.9], 81.8 [36.0-111.5], and
      58.0 [25.4-79.5], respectively, p < 0.05, compared with 209.3 [29.8-239.6] during
      spontaneous breathing). Compared with the facemask, the helmet with the same
      settings worsened patient-ventilator synchrony, as indicated by longer triggering
      on and cycling-off delays (0.14 [0.11-0.20] seconds vs. 0.32 [0.26-0.43] seconds,
      p < 0.05; and 0.20 [0.08-0.24] seconds vs. 0.27 [0.25-0.35] seconds, p < 0.01,
      respectively). The specific settings significantly improved the triggering-on
      delay compared with the helmet without specific settings (p < 0.01). Tolerance
      was the same with the three methods. CONCLUSIONS: Our results suggest that
      increasing both the pressure-support level and positive end-expiratory pressure
      and using the highest pressurization rate may be advisable when providing NPSV
      via a helmet.

PMID- 19384210
TI  - A safe citrate anticoagulation protocol with variable treatment efficacy and
      excellent control of the acid-base status.
AB  - OBJECTIVE: Citrate anticoagulation is an excellent alternative to heparin
      anticoagulation for critically ill patients requiring continuous renal
      replacement therapy. In this article, we provide a safe and an easy-to-handle
      citrate anticoagulation protocol with variable treatment doses and excellent
      control of the acid-base status. DESIGN: Prospective observational study.
      SETTING: University hospital. PATIENTS: One hundred sixty-two patients with acute
      renal failure requiring renal replacement therapy were enrolled in the study.
      INTERVENTION: A continuous venovenous hemodialysis-based citrate anticoagulation
      protocol using a 4% trisodium solution, a specially designed dialysate fluid, and
      a continuous calcium infusion were used. The study period was 6 days. Hemofilters
      were changed routinely after 72 hours of treatment. The patients were grouped
      according to body weight, with patients below 60 kg body weight in group 1,
      patients with at least 60 kg and up to 90 kg body weight in group 2, and patients
      with a body weight of above 90 kg in group 3. Dialysate flow was adapted
      according to body size and matched approximately 2 L/hr for a patient with
      average body size. Blood flow, citrate flow, and calcium flow were adjusted
      according to the dialysate flow used. MEASUREMENTS AND MAIN RESULTS: Median
      filter run time was 61.5 hours (interquartile range: 34.5-81.1 hours). Only 5% of
      all hemofilters had to be changed because of clotting. The prescribed treatment
      dose was achieved in all patients. Acid-base and electrolyte control were
      excellent in all groups. In the rare cases of metabolic disarrangement during
      citrate anticoagulation, acid-base values were rapidly corrected by modifying
      either the dialysate flow or alternatively the blood flow rate. Eight patients
      (5%) developed signs of citrate accumulation indicated by an increase of the
      total calcium >3 mmol/L or a need for high calcium substitution. CONCLUSIONS: We
      provide a safe and an easy-to-handle citrate anticoagulation protocol that allows
      an excellent acid-base and electrolyte control in critically ill patients with
      acute renal failure. The protocol can be adapted to patients' need, allowing a
      wide spectrum of treatment doses.

PMID- 19384211
TI  - Does perioperative hemodynamic optimization protect renal function in surgical
      patients? A meta-analytic study.
AB  - OBJECTIVE: Postoperative acute deterioration in renal function, producing
      oliguria and/or increase in serum creatinine, is one of the most serious
      complication in surgical patients. Most cases are due to renal hypoperfusion as a
      consequence of systemic hypotension, hypovolemia, and cardiac dysfunction.
      Although some evidence suggests that perioperative monitoring and manipulation of
      oxygen delivery by volume expansion and inotropic drugs may decrease mortality in
      surgical patients, no study analyzed this approach on postoperative renal
      dysfunction. The objective of this investigation is to perform a meta-analysis on
      the effects of perioperative hemodynamic optimization on postoperative renal
      dysfunction. DATA SOURCES, STUDY SELECTION, DATA EXTRACTION: A systematic
      literature review, using MEDLINE, EMBASE, and The Cochrane Library databases
      through January 2008 was conducted and 20 studies met the inclusion criteria
      (4220 participants). Data synthesis was obtained by using odds ratio (OR) with
      95% confidence interval (CI) by random-effects model. DATA SYNTHESIS:
      Postoperative acute renal injury was significantly reduced by perioperative
      hemodynamic optimization when compared with control group (OR 0.64; CI 0.50-0.83;
      p = 0.0007). Perioperative optimization was effective in reducing renal injury
      defined consistently with risk, injury, failure, and loss and end-stage kidney
      disease and Acute Kidney Injury Network classifications, and in studies defining
      renal dysfunction by serum creatinine and/or need of renal replacement therapy
      only (OR 0.66; CI 0.50-0.88; p = 0.004). The occurrence of renal dysfunction was
      reduced when treatment started both preoperatively and intraoperatively or
      postoperatively, was performed in high-risk patients, and was obtained by fluids
      and inotropes. Mortality was significantly reduced in treatment group (OR 0.50;
      CI 0.31-0.80; p = 0.004), but statistical heterogeneity was observed.
      CONCLUSIONS: Surgical patients receiving perioperative hemodynamic optimization
      are at decreased risk of renal impairment. Because of the impact of postoperative
      renal complications on adverse outcome, efforts should be aimed to identify
      patients and surgery that would most benefit from perioperative optimization.

PMID- 19384212
TI  - The effect of increasing doses of norepinephrine on tissue oxygenation and
      microvascular flow in patients with septic shock.
AB  - OBJECTIVE: To investigate the effect of escalating doses of norepinephrine, aimed
      at achieving incremental increases in mean arterial pressure (MAP), on
      microvascular flow and tissue oxygenation in patients with septic shock. DESIGN:
      Single-center interventional study. SETTING: University hospital intensive care
      unit. PATIENTS: Sixteen patients with established septic shock. INTERVENTIONS:
      The norepinephrine dose was escalated to achieve incremental increases in the MAP
      from 60 to 70, 80, and 90 mm Hg. MEASUREMENTS AND MAIN RESULTS: In addition to
      routine clinical measurements, cardiac output was determined using lithium
      dilution and arterial waveform analysis, cutaneous tissue Pto2 was measured using
      a Clark electrode, cutaneous red blood cell flux was assessed using laser Doppler
      flowmetry, and sublingual microvascular flow was evaluated using sidestream
      darkfield imaging. The mean (sd) norepinephrine dose increased from 0.18 (0.18)
      microg x kg(-1) x min(-1) at 60 mm Hg to 0.41 (0.26) microg x kg(-1) x min(-1) at
      90 mm Hg (p < 0.0001). During this period, global oxygen delivery increased from
      487 (418-642) to 662 (498-829) mL x min(-1) x m(-2) (p < 0.01), cutaneous Pto2
      increased from 44 (11) to 54 (13) mm Hg (p < 0.0001) and cutaneous microvascular
      red blood cell flux increased from 26.1 (16.2-41.9) to 33.3 (20.3-46.7) perfusion
      units (p < 0.05). No changes in sublingual microvascular flow index, vessel
      density, the proportion of perfused vessels, perfused vessel density, or
      heterogeneity index were identified by sidestream darkfield imaging. CONCLUSIONS:
      In patients with septic shock, targeting higher MAP by increasing the dose of
      norepinephrine resulted in an increase in global oxygen delivery, cutaneous
      microvascular flow, and tissue oxygenation. There were no changes in preexisting
      abnormalities of sublingual microvascular flow. Further research is required to
      clarify the optimal end points for vasopressor therapy in patients with septic
      shock.

PMID- 19384213
TI  - Brain tissue oxygen and outcome after severe traumatic brain injury: a systematic
      review.
AB  - OBJECTIVE: In this study, available medical literature were reviewed to determine
      whether brain hypoxia as measured by brain tissue oxygen (Bto2) levels is
      associated with increased risk of poor outcome after traumatic brain injury
      (TBI). A secondary objective was to examine the safety profile of a direct BtO2
      probe. DATA SOURCE AND EXTRACTION: Clinical studies published between 1993 and
      2008 were identified from electronic databases, Index Medicus, bibliographies of
      pertinent articles, and expert consultation. The following inclusion criteria
      were applied for outcome analysis: 1) more than 10 patients described, 2) use of
      a direct Bto2 monitor, 3) brain hypoxia defined as Bto2 <10 mm Hg for >15 or 30
      minutes, 4) 6-month outcome data, and 5) clear reporting of patient outcome
      associated with Bto2. For the analysis, each selected article had to have
      adequate data to determine odds ratios (ORs) and confidence intervals (CIs).
      Thirteen studies met the initial inclusion criteria and three were included in
      the final outcome analysis. Safety data were abstracted from any report where it
      was mentioned. DATA SYNTHESIS: The three studies included 150 evaluable patients
      with severe TBI (Glasgow Coma Scale <or=8). Brain hypoxia was identified in 71
      (47%) of these patients. Among the patients with brain hypoxia, 52 (73%) had
      unfavorable outcome including 39 (55%) who died. In the absence of brain hypoxia,
      34 (43%) patients had an unfavorable outcome, including 17 (22%) who died.
      Overall brain hypoxia (Bto2 <10 mm Hg >15 minutes) was associated with worse
      outcome (OR 4.0; 95% CI 1.9-8.2) and increased mortality (OR 4.6; 95% CI 2.2
      9.6). We reviewed published safety data; in 292 patients monitored with a Bto2
      probe, only two adverse events were reported. CONCLUSION: Summary results
      indicate that brain hypoxia (<10 mm Hg) is associated with worse outcome after
      severe TBI and that Bto2 probes are safe. These results imply that treating
      patients to increase Bto2 may improve outcome after severe TBI. This question
      will require further study.

PMID- 19384215
TI  - The presence of a family witness impacts physician performance during simulated
      medical codes.
AB  - OBJECTIVE: To determine whether the presence and behavior of a family witness to
      cardiopulmonary resuscitation (CPR) impacts critical actions performed by
      physicians. DESIGN: This was a randomized comparison study of physicians'
      performance during a simulated cardiac arrest with three different family witness
      states. SETTING: This study was conducted at the Wayne State University Eugene
      Applebaum College of Pharmacy and Health Science's Center for Healthcare
      Simulation. SUBJECTS: Second-year and third-year emergency medicine (EM)
      residents from the Wayne State University Department of Emergency Medicine
      affiliated residency programs and Michigan State University-affiliated EM
      residency programs. INTERVENTION: Thirty teams comprised of one second-year and
      one third-year EM resident were randomly assigned to one of the three groups: 1)
      no family witness; 2) a nonobstructive "quiet" family witness; and 3) a family
      witness displaying an overt grief reaction. MEASUREMENTS AND MAIN RESULTS: Each
      pair was assessed for time to critical actions (e.g., minutes to CPR and drug
      administration) and for resuscitation-based performance outcomes (e.g., number of
      shocks) during a simulated cardiac arrest. The time to critical events was
      similar across groups with respect to initiating CPR, attempting to intubate the
      patient, and pronouncing the death of the patient. However, the time to deliver
      the first defibrillation shock was longer for the overt reaction witness group
      (2.57 minutes) as compared with the quiet (1.77 minutes) and no family witness
      (1.67 minutes) groups. Additionally, fewer total shocks were delivered in the
      overt reaction witness groups (4.0 minutes) vs. the quiet (6.5 minutes) and no
      family witness groups (6.0 minutes). CONCLUSION: The presence of a family witness
      may have a significant impact on physicians' ability to perform critical actions
      during simulated medical resuscitations. Further study is necessary to see if
      this effect crosses over into real clinical practice and if training ameliorates
      this effect.

PMID- 19384214
TI  - A simple clinical predictive index for objective estimates of mortality in acute
      lung injury.
AB  - OBJECTIVE: We sought to develop a simple point score that would accurately
      capture the risk of hospital death for patients with acute lung injury (ALI).
      DESIGN: This is a secondary analysis of data from two randomized trials. Baseline
      clinical variables collected within 24 hours of enrollment were modeled as
      predictors of hospital mortality using logistic regression and bootstrap
      resampling to arrive at a parsimonious model. We constructed a point score based
      on regression coefficients. SETTING: Medical centers participating in the Acute
      Respiratory Distress Syndrome Clinical Trials Network (ARDSnet). PATIENTS: Model
      development: 414 patients with nontraumatic ALI participating in the low tidal
      volume arm of the ARDSnet Acute Respiratory Management in ARDS study. Model
      validation: 459 patients participating in the ARDSnet Assessment of Low tidal
      Volume and elevated End-expiratory volume to Obviate Lung Injury study. Model
      Validation: 459 patients participating in the ARDSnet Assessment of Low tidal
      Volume and elevated End-expiratory volume to Obviate Lung Injury trial.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Variables comprising the
      prognostic model were hematocrit <26% (1 point), bilirubin >or=2 mg/dL (1 point),
      fluid balance >2.5 L positive (1 point), and age (1 point for age 40-64 years, 2
      points for age >or=65 years). Predicted mortality (95% confidence interval) for
      0, 1, 2, 3, and 4+ point totals was 8% (5% to 14%), 17% (12% to 23%), 31% (26% to
      37%), 51% (43% to 58%), and 70% (58% to 80%), respectively. There was an
      excellent agreement between predicted and observed mortality in the validation
      cohort. Observed mortality for 0, 1, 2, 3, and 4+ point totals in the validation
      cohort was 12%, 16%, 28%, 47%, and 67%, respectively. Compared with the Acute
      Physiology Assessment and Chronic Health Evaluation III score, areas under the
      receiver operating characteristic curve for the point score were greater in the
      development cohort (0.72 vs. 0.67, p = 0.09) and lower in the validation cohort
      (0.68 vs. 0.75, p = 0.03). CONCLUSIONS: Mortality in patients with ALI can be
      predicted using an index of four readily available clinical variables with good
      calibration. This index may help inform prognostic discussions, but validation in
      nonclinical trial populations is necessary before widespread use.

PMID- 19384216
TI  - A multicenter, randomized, double-blind, placebo-controlled, dose-escalation
      trial assessing safety and efficacy of active site inactivated recombinant factor
      VIIa in subjects with acute lung injury or acute respiratory distress syndrome.
AB  - OBJECTIVE: To evaluate the safety and efficacy of active site inactivated
      recombinant factor VIIa (FFR-rFVIIa) in patients with acute respiratory distress
      syndrome. DESIGN: Phase II, randomized, double-blind, placebo-controlled, dose
      escalation trial. SETTING: Forty-six intensive care units (ICU) in ten countries.
      PATIENTS: All adult (>or=18 years), mechanically ventilated patients with acute
      onset (within 48 hour) of acute lung injury/acute respiratory distress syndrome
      were included. INTERVENTIONS: Four sequential (in ascending order) treatment
      groups (cohorts) in single and multiple dosing strategies. Subjects were
      randomized in a 2:1 ratio to either FFR-rFVIIa or placebo within each cohort.
      MEASUREMENTS AND RESULTS: Data were collected daily for 7 days and on days 14 and
      28 for efficacy variables including hematology and coagulation parameters, plasma
      d-dimer levels, plasma interleukin-6 levels, vital signs, ventilator parameters,
      lung injury score, and Sequential Organ Failure Assessment score. The study was
      discontinued prematurely by the Safety Committee based on statistical analysis of
      the mortality in cohort 3 (4 x 400 microg/kg), which suggested that, after
      adjusting for prognostic covariates, 28-day mortality was significantly higher in
      this cohort than in the placebo group and time to death was significantly
      shorter. A total of 214 patients (147 male) were included in the trial, mean age
      59 years (range, 24-85 years). Overall, there were no significant differences in
      mortality rates in treated and placebo patients (36/144 deaths FFR-rFVIIa, 15/70
      placebo). There was no treatment effect of FFR-rFVIIa on vital signs, blood
      chemistry parameters, hematology parameters, or amount of transfusion products
      required. There was a trend to increased bleeding with increasing FFR-rFVIIa
      dose. CONCLUSION: In this randomized double-blind, placebo- controlled, dose
      escalation trial, FFR-rFVIIa had no beneficial effects on morbidity or outcome
      overall. The cohort of patients receiving 4 x 400 g/kg of FFR-rFVIIa had
      increased mortality rates compared with placebo-treated patients, and there was a
      trend to increased risk of serious bleeding with increasing doses.

PMID- 19384217
TI  - Staphylococcus aureus alpha-toxin and Escherichia coli hemolysin impair cardiac
      regional perfusion and contractile function by activating myocardial eicosanoid
      metabolism in isolated rat hearts.
AB  - OBJECTIVE: In sepsis, cardiac function is frequently depressed. Microcirculatory
      disturbances as evidenced in most organs may extend to the coronary circulation
      and may play a role in the occurrence of cardiac dysfunction. Staphylococcal
      alpha-toxin and Escherichia coli hemolysin (ECH), pore-forming exotoxins of
      clinically relevant bacteria, have recently been demonstrated to evoke cardiac
      dysfunction in isolated rat hearts by activating myocardial eicosanoid
      metabolism. alpha-Toxin activates synthesis of thromboxane (Tx) A2, ECH of
      cysteinyl-leukotrienes (Sibelius U, Grandel U, Buerke M, et al: Leukotriene
      mediated coronary vasoconstriction and loss in myocardial contractility evoked by
      low doses of Escherichia coli hemolysin in perfused reat hearts. Crit Care Med
      2003; 3:683-688, Sibelius U, Grandel U, Buerke M, et al: Staphylococcal alpha
      toxin provokes coronary vasoconstriction and loss in myocardial contractility in
      perfused rat hearts-Role of Tx formation. Circulation 2000; 101:78-85). We now
      investigated whether cardiac dysfunction in response to alpha-toxin and ECH is
      caused by disturbances of regional cardiac perfusion. DESIGN: A prospective,
      experimental study. SETTING: A research laboratory at a university hospital.
      SUBJECTS: Isolated hearts from male Wistar rats. INTERVENTIONS: Changes of
      regional perfusion were investigated by using colored microspheres in isolated
      rat hearts perfused with alpha-toxin or ECH either at constant coronary perfusion
      pressure or constant coronary flow rate. Significance of toxin-activated
      eicosanoid generation was evaluated by pharmacologic interventions. MEASUREMENTS
      AND MAIN RESULTS: By eliciting eicosanoid formation, both toxins caused an
      increase in coronary vascular resistance and a loss in contractile function. In
      ECH-perfused hearts, reduction of regional perfusion predominantly occurred in
      subendocardial sections in either perfusion mode (coronary perfusion pressure or
      coronary flow rate). When synthesis of cysteinyl-leukotrienes was blocked by the
      5-lipooxygenase inhibitor MK-886, disturbances of regional perfusion and the
      associated cardiac dysfunction were largely prevented. Coronary perfusion of
      alpha-toxin caused a decrease of regional perfusion that was more pronounced in
      subepicardial layers. Inhibiting the release of TxA2 by blocking the
      cyclooxygenase with indomethacin attenuated the perfusion abnormalities and the
      cardiodepression in response to alpha-toxin. CONCLUSIONS: Bacterial exotoxins of
      clinically relevant bacteria may impair cardiac function by eliciting distinct
      coronary perfusion abnormalities via release of vasoactive eicosanoids.

PMID- 19384218
TI  - N-acetylcysteine is associated with increased blood loss and blood product
      utilization during cardiac surgery.
AB  - OBJECTIVE: When used to prevent perioperative inflammation and ischemia
      reperfusion injury, N-acetylcysteine may inadvertently impair hemostasis. We,
      therefore, performed a post hoc analysis of a recent randomized controlled trial
      in cardiac surgery to determine whether N-acetylcysteine was associated with
      increased blood loss and blood product transfusion. DESIGN: Blinded (patients,
      caregivers, outcome assessors) placebo-controlled parallel group randomized trial
      (www.ClinicalTrials.gov ID NCT00188630). SETTING: Tertiary care hospital in
      Toronto, Ontario, Canada (September 2003 to October 2005). PATIENTS: A total of
      177 patients with preexisting moderate renal insufficiency (estimated glomerular
      filtration rate <or=60 mL/min) and undergoing cardiac surgery. INTERVENTIONS:
      Eighty-nine patients were randomized to receive intravenous N-acetylcysteine (100
      mg/kg bolus; 20 mg.kg.hr infusion until 4 hours after cardiopulmonary bypass),
      and 88 were randomized to receive placebo. MEASUREMENTS AND MAIN RESULTS: We used
      laboratory markers (hemoglobin, platelets, coagulation), chest-tube blood loss,
      and blood product transfusion to evaluate hemostasis. Compared with placebo,
      patients who received N-acetylcysteine arm experienced a mean 24-hour chest-tube
      blood loss that was 261 mL higher (95% confidence interval [CI] 93-488 mL, p =
      0.008), and were transfused 1.6 more units of red blood cells (95% CI 0.4-3.1
      units, p = 0.02) during hospitalization. The risk of receiving >or=5 units of red
      blood cells within 24 hours of surgery was significantly higher with N
      acetylcysteine (relative risk 1.85, 95% CI 1.06-3.21, p = 0.03; adjusted relative
      risk 2.09, 95% CI 1.24-3.83, p = 0.005). CONCLUSIONS: In patients who have
      preexisting moderate renal insufficiency and are undergoing cardiac surgery, N
      acetylcysteine was associated with important effects on blood loss and blood
      product transfusion. Clinicians and researchers should, therefore, consider the
      potential for impaired hemostasis when using N-acetylcysteine in the
      perioperative setting. Further research is needed to elucidate mechanisms by
      which N-acetylcysteine may impair hemostasis, and the risk-benefit profile of N
      acetylcysteine for perioperative organ protection.

PMID- 19384219
TI  - Active cytomegalovirus infection is common in mechanically ventilated medical
      intensive care unit patients.
AB  - OBJECTIVE: To assess the incidence, risk factors, and outcome of active
      cytomegalovirus (CMV) infection in nonimmunosuppressed intensive care unit (ICU)
      patients. DESIGN: Prospective epidemiologic study. SETTING: A medical ICU in a
      university hospital. PATIENTS: Two hundred forty-two nonimmunosuppressed ICU
      patients mechanically ventilated for >or=2 days. INTERVENTIONS: Routine pp65
      antigenemia and serology for CMV were performed at admission, and then weekly.
      Bronchoalveolar lavage viral cultures were done when pneumonia was suspected.
      MEASUREMENTS AND MAIN RESULTS: Thirty-nine of the 242 ICU patients (16.1%,
      confidence interval 11.5% to 20.7%) developed an active CMV infection, as
      diagnosed by positive antigenemia (85%) and/or positive rapid viral culture in
      bronchoalveolar lavage (26%). Antiviral treatment was initiated in 21 (54%)
      patients. ICU mortality (54% vs. 37%, p = 0.082) and in-hospital mortality (59%
      vs. 41%, p = 0.058) were increased in patients with active CMV infection, as
      compared with those without active CMV infection. Active CMV infection and
      Simplified Acute Physiology Score II at admission were associated with ICU death
      on multivariate analysis. The patients with active CMV infection had longer
      mechanical ventilation and longer ICU stay and were significantly more prone to
      developing bacterial nosocomial infections (p < 0.001). Logistic regression
      analysis showed that prior admission to other wards (p = 0.043; odds ratio [OR],
      2.49), blood transfusions (p = 0.04; OR, 3.31), enteral feeding (p = 0.005; OR,
      3.00), recent corticosteroid use before ICU admission (p = 0.08; OR, 2.26), and
      age (p = 0.07; OR, 1.026) were associated with the occurrence of active CMV
      infection. CONCLUSIONS: : Active CMV infection is common among previously healthy
      patients under mechanical ventilation in a medical ICU. Further studies are
      needed to evaluate the role of antiviral treatments to reduce both the incidence
      and the outcome impact of active CMV infection.

PMID- 19384220
TI  - The effect of daily bathing with chlorhexidine on the acquisition of methicillin
      resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and
      healthcare-associated bloodstream infections: results of a quasi-experimental
      multicenter trial.
AB  - OBJECTIVE: Spread of multidrug-resistant organisms within the intensive care unit
      (ICU) results in substantial morbidity and mortality. Novel strategies are needed
      to reduce transmission. This study sought to determine if the use of daily
      chlorhexidine bathing would decrease the incidence of colonization and
      bloodstream infections (BSI) because of methicillin-resistant Staphylococcus
      aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) among ICU patients.
      DESIGN, SETTING, AND PATIENTS: Six ICUs at four academic centers measured the
      incidence of MRSA and VRE colonization and BSI during a period of bathing with
      routine soap for 6 months and then compared results with a 6-month period where
      all admitted patients received daily bathing with a chlorhexidine solution.
      Changes in incidence were evaluated by Poisson and segmented regression modeling.
      INTERVENTIONS: Daily bathing with a chlorhexidine-containing solution.
      MEASUREMENTS AND MAIN RESULTS: Acquisition of MRSA decreased 32% (5.04 vs. 3.44
      cases/1000 patient days, p = 0.046) and acquisition of VREdecreased 50% (4.35 vs.
      2.19 cases/1000 patient days, p = 0.008) following the introduction of daily
      chlorhexidine bathing. Segmented regression analysis demonstrated significant
      reductions in VRE bacteremia (p = 0.02) following the introduction of
      chlorhexidine bathing. VRE-colonized patients bathed with chlorhexidine had a
      lower risk of developing VRE bacteremia (relative risk 3.35; 95% confidence
      interval 1.13-9.87; p = 0.035), suggesting that reductions in the level of
      colonization led to the observed reductions in BSI. CONCLUSION: We conclude that
      daily chlorhexidine bathing among ICU patients may reduce the acquisition of MRSA
      and VRE. The approach is simple to implement and inexpensive and may be an
      important adjunctive intervention to barrier precautions to reduce acquisition of
      VRE and MRSA and the subsequent development of healthcare-associated BSI.

PMID- 19384221
TI  - The impact of delirium on clinical outcomes in mechanically ventilated surgical
      and trauma patients.
AB  - OBJECTIVE: Previously, delirium has been identified as an independent risk factor
      for mortality in critically ill medical patients. We undertook this study to
      examine the relationships among medication usage, delirium, and clinical outcomes
      in a critically ill surgical/trauma population. DESIGN: Prospective,
      multicentered, observational study. SETTING: Two surgical intensive care units in
      level 1 trauma centers. PATIENTS: One hundred thirty-four consecutive surgical
      adult patients requiring mechanical ventilation (MV) for greater than 24 hours.
      INTERVENTIONS: Daily delirium assessment with the Confusion Assessment Method
      Intensive Care Unit tool, outcomes assessment, and prospective data collection.
      MEASUREMENT AND MAIN RESULTS: Of the 134 patients who met inclusion criteria, 84
      patients (63%) developed delirium at some point during their intensive care unit
      (ICU) stay. Delirium was associated with more MV days (9.1 vs. 4.9 days, p <
      0.01), longer ICU stay (12.2 vs. 7.4 days, p < 0.01), longer hospital stay (20.6
      vs. 14.7 days, p < 0.01). Additionally, greater cumulative lorazepam dose (p =
      0.012), and higher cumulative fentanyl dose (p = 0.035) were administered in the
      delirium group. CONCLUSIONS: Delirium in the surgical/trauma ICU cohort is
      independently associated with more days requiring MV, longer ICU length of stay,
      and longer hospital length of stay. Additionally, greater amounts of lorazepam
      and fentanyl were administered to patients with delirium.

PMID- 19384222
TI  - Low arginine/asymmetric dimethylarginine ratio deteriorates systemic hemodynamics
      and organ blood flow in a rat model.
AB  - OBJECTIVE: Both arginine and asymmetric dimethylarginine (ADMA) play a crucial
      role in the arginine-nitric oxide pathway. Low arginine and high ADMA levels can
      be found in critically ill patients after major surgery. The aim of this study
      was to evaluate the effects of low arginine plasma concentrations in combination
      with high ADMA plasma concentrations on hemodynamics and organ blood flow.
      DESIGN: Randomized, placebo-controlled animal laboratory investigation. SUBJECTS:
      Male Wistar rats (n = 21), anesthetized. INTERVENTIONS: Rats were randomly
      assigned to three groups: a control group, an ADMA group, or an arginase
      (ASE)/ADMA group. In the control group, rats received (at t = 0) an intravenous
      (IV) infusion of 1.5 mL 0.9% NaCl during a 20-minute period. After 60 minutes (t
      = 60), rats received an IV bolus of 1.0 mL 0.9% NaCl. In the ADMA group, rats
      received an IV infusion of 1.5 mL 0.9% NaCl during a 20-minute period and at t =
      60 an IV bolus of 1.0 mL ADMA (20 mg/kg). In the ASE/ADMA group, rats received an
      IV infusion of 1.5 mL ASE (3200 IU) solution during a 20-minute period and at t =
      60 an IV bolus of 1.0 mL ADMA (20 mg/kg). MEASUREMENTS AND MAIN RESULTS: Infusion
      of ADMA (20 mg/kg) and ASE (3200 IU) resulted in increased plasma ADMA levels and
      decreased arginine levels. During the whole experiment, systemic hemodynamics
      (heart rate, mean arterial pressure [MAP], and cardiac output) were measured. In
      addition, organ blood flow was measured at t = 90 and t = 180 minutes, using
      fluorescent microspheres. Compared with the control group, MAP and systemic
      vascular resistance were increased after infusion of ADMA. Infusion of ASE in
      combination with ADMA significantly deteriorated systemic hemodynamics (MAP,
      cardiac output, stroke volume, and systemic vascular resistance) and organ blood
      flow through the kidney and spleen. In addition, an initial decrease in arterial
      flow, followed by a later major increase, and panlobular apoptosis and necrosis
      of the liver was observed. CONCLUSIONS: The current study shows that low arginine
      plasma levels in combination with high ADMA plasma levels deteriorates systemic
      hemodynamics and reduces blood flow through the kidney and spleen and liver.
      These data suggest that a diminished nitric oxide production may be involved in
      the onset of organ failure.

PMID- 19384223
TI  - Influence of red blood cell transfusion on mortality and long-term functional
      outcome in 292 patients with spontaneous subarachnoid hemorrhage.
AB  - OBJECTIVE: To analyze the influence of red blood cell (RBC) transfusions on
      mortality and outcome of patients with spontaneous subarachnoid hemorrhage (SAH)
      and to determine predictors of unfavorable neurologic long-term outcome in this
      patient population. DESIGN: Cohort study with post-intensive care unit (ICU)
      prospective evaluation of functional long-term outcome. SETTING: Ten-bed neuro
      ICU in a tertiary care university hospital. PATIENTS: A consecutive cohort of 292
      patients with spontaneous SAH admitted to a neuro-ICU during a 70-month period.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 292 consecutive
      patients with SAH were enrolled in the study. At admission, mean hemoglobin was
      13.3 g/dL (+/-sd 1.8 g/dL), comparable in all Hunt and Hess groups (p = 0.61 by
      analysis of variance). Seventy-nine patients received at least one unit of RBC
      transfusion in the study period. In-ICU mortality was 20.5% (n = 60). Binary
      logistic regression analysis comparing survivors with nonsurvivors found only
      higher Hunt and Hess grades (i.e., Hunt and Hess 3-5) to be significantly (p <
      0.01) associated with mortality in the neuro-ICU, whereas transfusion, sex, and
      even age had no significant influence. Functional long-term outcome was assessed
      after a mean of 3.3 years (sd +/-1.7 years) by evaluating modified Rankin Scale
      (mRS) and Glasgow Outcome Scale (GOS). More than 41% of all patients have almost
      fully recovered (i.e., mRS 0-1; GOS 4-5). Factors associated with unfavorable
      long-term outcome (i.e., GOS 1-3 and mRS 2-6) were age (odds ratio 1.06; 95%
      confidence interval 1.03-1.09; p < 0.01), Hunt and Hess Grade (odds ratio 11.43;
      95% confidence interval 4.1-31.9; p < 0.01) but not transfusion (p = 0.46).
      CONCLUSION: Transfusion of RBCs was not associated with in-neuro-ICU mortality or
      unfavorable long-term outcome. Of all patients with SAH, >41% have almost fully
      recovered with favorable neurologic long-term outcome.

PMID- 19384224
TI  - Procalcitonin as a prognostic and diagnostic tool for septic complications after
      major trauma.
AB  - OBJECTIVE: The primary aim of this study was to investigate the diagnostic value
      of procalcitonin (PCT) and C-reactive protein (CRP) in septic complications after
      major trauma. A secondary aim was to determine whether there was a prognostic
      value of PCT for severity of injury, organ dysfunction, and sepsis. DESIGN:
      Prospective study. SETTING: Medical/surgical intensive care unit (ICU). PATIENTS:
      Ninety-four patients with consecutive trauma >or=16 years who were admitted to
      the ICU for an expected stay of >24 hours. INTERVENTIONS: None. MEASUREMENTS: PCT
      and CRP were collected at admission and every day thereafter. The American
      College of Chest Physicians/Society of Critical Care Medicine Consensus
      Conference definition was used to identify sepsis criteria. The Sequential Organ
      Failure Assessment score was used to describe the severity of organ dysfunction.
      We retrospectively analyzed the occurrence of systemic inflammatory response
      syndrome and sepsis using the collected variables (criteria fulfilled at least
      during three continuous days). MAIN RESULTS: Patients with trauma presented an
      early and significant increase in PCT at the moment of septic complications
      compared with concentrations measured 1 day before the diagnosis of sepsis: 0.85
      vs. 3.32 ng/mL for PCT (p < 0.001) and 135 vs. 175 mg/L for CRP (p = not
      significant). The areas under the respective curve at admission in the diagnosis
      of sepsis were 0.787 (p < 0.001) and 0.489 for PCT and CRP, respectively.
      CONCLUSION: PCT plasma reinduction marks possible septic complication during
      systemic inflammatory response syndrome after major trauma. In addition, high PCT
      concentration at admission after trauma in ICU patients indicates an increased
      risk of septic complications.

PMID- 19384225
TI  - Duodenal versus gastric feeding in medical intensive care unit patients: a
      prospective, randomized, clinical study.
AB  - OBJECTIVE: To determine whether medical intensive care unit (ICU) patients
      receiving nasoduodenal (ND) feedings achieve optimal nutritional support and
      better clinical outcomes compared with patients receiving nasogastric (NG)
      feedings. DESIGN: A prospective, randomized, clinical study. SETTING: Medical ICU
      of a university-affiliated tertiary medical center. PATIENTS: One hundred twenty
      one medical ICU patients required enteral feeding. INTERVENTIONS: Patients were
      randomized to receive enteral feeding. One group received ND feedings and the
      other group received NG feedings. All patients followed the same protocol.
      MEASUREMENTS AND MAIN RESULTS: The primary outcome of optimal nutritional support
      was assessed by measurement of time to goal tube feed rate and daily calorie and
      protein intake. Secondary clinical outcomes included number of ICU, hospital and
      ventilator days, number of the days in the study, blood-glucose levels, incidence
      of vomiting, diarrhea, gastrointestinal bleeding, tube replaced, tube clogged,
      fever, bacteremia, and ventilator-associated pneumonia (VAP), and mortality rate.
      Results showed that the ND group had a higher average daily calorie and protein
      intake compared with NG group and achieved nutritional goals earlier. In terms of
      clinical outcomes, patients in the ND group had a lower rate of vomiting and VAP.
      The other clinical outcomes such as number of ICU days, hospital days, ventilator
      days, blood-glucose level, tube replaced or clogged, diarrhea, gastrointestinal
      bleeding, fever, bacteremia, and mortality rate were not significantly different
      between two groups. CONCLUSIONS: Patients who received ND feedings achieved
      nutritional goals earlier than those who received NG feeding. ND feeding group
      also has a lower rate of vomiting and VAP in the medical ICU setting.

PMID- 19384226
TI  - Lung injury after hemorrhage is age dependent: role of peroxisome proliferator
      activated receptor gamma.
AB  - OBJECTIVE: The incidence of multiple organ failure in pediatric trauma victims is
      lower than in the adult population. However, the molecular mechanisms are not yet
      defined. We investigated whether the pathophysiologic characteristics of
      hemorrhage-induced lung injury may be age dependent and may be regulated by the
      peroxisome proliferator-activated receptor gamma (PPARgamma). DESIGN:
      Prospective, laboratory investigation that used an established rodent model of
      hemorrhagic shock. SETTING: University hospital laboratory. SUBJECTS: Young (n =
      67; 3-5 months old) and mature (n = 66; 11-13 months old) male rats.
      INTERVENTIONS: Hemorrhagic shock was induced in young and mature rats by
      withdrawing blood to a mean arterial blood pressure of 50 mm Hg. After 3 hours,
      rats were rapidly resuscitated by infusing the shed blood and killed 3 hours
      thereafter. MEASUREMENTS AND MAIN RESULTS: In young rats, lung injury was
      characterized by accumulation of red cells and neutrophils at the end of the
      resuscitation period; on Western blot analysis, lung expression of intercellular
      adhesion molecule-1 was increased. In contrast, the severity of lung injury was
      more pronounced in mature rats. Lung myeloperoxidase activity and expression of
      constitutive and inducible intercellular adhesion molecule-1 was significantly
      higher in mature rats compared with young rats. Mature rats also had higher
      plasma levels of cytokines and chemokines compared with young rats. This
      heightened inflammation was associated with higher degree of activation of
      nuclear factor-kappaB and down-regulation of PPARgamma and heat shock factor-1 in
      the lung of mature rats compared with young rats. Treatment with the PPARgamma
      ligand, the cyclopentenone prostaglandin 15-deoxy-Delta-prostaglandin J2,
      ameliorated lung injury in young, but not in mature animals. CONCLUSIONS: Lung
      injury after severe hemorrhage is age dependent and may be secondary to a diverse
      regulation of PPARgamma.

PMID- 19384227
TI  - Emergency trauma score: an instrument for early estimation of trauma severity.
AB  - OBJECTIVES: Early estimation of the mortality risk of severely injured patients
      is mandatory. To estimate the seriousness of the condition of patients with
      trauma, we developed the emergency trauma score (EMTRAS) for ease of use, with
      simple parameters that are available within 30 minutes. DESIGN: Prospective
      analysis of the German Trauma Registry of multitrauma patients. SETTING: EMTRAS
      was derived from data from 1993 through 2003. Potential parameters that were
      prognostic for mortality in univariate analysis were evaluated by multivariate
      binary logistic regression. Selected parameters were then assigned a subscore
      that varied from 0 to 3. The EMTRAS score was a simple addition of these
      subscores. EMTRAS was compared with other scores' receiver operating
      characteristic curves. After completion, EMTRAS was validated in patients from
      2004 and 2005. PATIENTS: A total of 11,533 patients were to be used for
      developing the score and 3314 patients for validating it. MAIN RESULTS: The
      strongest predictors of mortality were age, prehospital Glasgow Coma Scale, base
      excess (mmol/L), and prothrombin time (% of reference). These parameters were
      categorized in subscores of 0 through 3. Age: <40, 40 through 60, 61 through 75,
      and >75 scored 0, 1, 2, and 3, respectively. Glasgow Coma Scale: 13 through 15,
      10 through 12, 6 through 9, and 3 through 5 scored 0, 1, 2, and 3, respectively.
      Base excess: >-1, -5 through -1, -10 through -5.1, and <-10 scored 0, 1, 2, and
      3, respectively. Prothrombin time: <80%, 80% through 50%, 49% through 20%, and
      >20% received a score of 0, 1, 2, and 3, respectively. In the validation dataset,
      the area under the receiver operating characteristic curve for EMTRAS was 0.828.
      CONCLUSIONS: EMTRAS combines four early parameters from the emergency room and
      accurately predicts mortality. Knowledge of the anatomical injuries is not
      necessary. The determination of the EMTRAS will inform caregivers of the
      seriousness of patients with trauma at an early stage.

PMID- 19384228
TI  - Early assessment of outcome in cardiogenic shock: relevance of plasma N-terminal
      pro-B-type natriuretic peptide and interleukin-6 levels.
AB  - OBJECTIVE: Plasma N-terminal pro-B-type natriuretic peptide (Nt-pro-BNP) levels
      are frequently elevated in critically ill patients and are associated with an
      increased mortality. In this study, we determined Nt-pro-BNP levels in patients
      with cardiogenic shock (CS) and evaluated its association with clinical and
      hemodynamic parameters and 30-day mortality. DESIGN: Retrospective study.
      SETTING: Two, eight-bed intensive care units at a university and a community
      hospital. PATIENTS: Retrospective study on stored plasma samples of 58 patients
      with CS, obtained at admission to the intensive care unit. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Massively elevated Nt-pro-BNP concentrations
      showed no significant association with duration of shock, total Sequential Organ
      Failure Assessment score, or invasive hemodynamic parameters at the time of blood
      sampling but a significant association with estimated glomerular filtration rate
      (p < 0.001), C-reactive protein (p = 0.03), age (p = 0.005), and body weight (p =
      0.03). Both in univariate and multivariate survival analyses, Nt-pro-BNP levels
      above the median (>12,782 pg/mL) were significant predictors of 30-day mortality
      (p < 0.001) and showed a complementary role with interleukin (IL)-6 in predicting
      outcome. Patients with IL-6 >195 pg/mL and Nt-pro-BNP above the median value had
      the highest 30-day mortality (93.7%), whereas patients with lower IL-6 levels
      together with lower Nt-pro-BNP levels had significantly better survival
      (mortality rate 26.3%). Among patients who had acute myocardial infarction, those
      with Nt-pro-BNP concentrations above the median level showed a highly impaired
      clinical course even if coronary revascularization was successful (30-day
      mortality 90.9% vs. 29.4%, p = 0.001), whereas survival of patients with
      unsuccessful revascularization did not differ significantly with respect to the
      median of Nt-pro-BNP (30-day survival rate 81.8% vs. 75.0%, p = 0.71).
      CONCLUSION: The massive elevations of Nt-pro-BNP observed in the early phase of
      CS seem to be independent of ventricular performance. Nt-pro-BNP levels are
      nevertheless predictive of 30-day survival in patients with CS especially in
      those with successful revascularization and might be used in combination with IL
      6 for estimation of outcome early on.

PMID- 19384229
TI  - Update on neuromuscular pharmacology.
AB  - PURPOSE OF REVIEW: We review the efficacy and safety of gantacurium and AV002,
      two novel, investigational fumarate-based nondepolarizing neuromuscular blockers,
      as well as sugammadex and cysteine, two novel reversal drugs that have no
      acetylcholinesterase inhibition properties. RECENT FINDINGS: Gantacurium (with a
      pharmacodynamic profile similar to that of succinylcholine) and AV002 (with an
      intermediate duration of action) have shown efficacy in animals and, for
      gantacurium, in humans. Animal data have shown that exogenous administration of
      the amino acid cysteine accelerates the natural chemical degradation of both
      gantacurium and AV002 via the cysteine adduction pathway. Another reversal drug,
      sugammadex (a modified gamma-cyclodextrin and the first selective relaxant
      binding agent), forms very tight complexes in a 1: 1 ratio with steroidal
      neuromuscular blocking agents. SUMMARY: In a multicenter phase-2 randomized
      controlled study in the European Union, the efficacy and safety of gantacurium
      were evaluated, but results have not yet been published. Sugammadex is currently
      available in the European Union, but the United States Food and Drug
      Administration has had concerns about its safety (hypersensitivity and allergic
      reactions) and has asked for additional safety data. It is hoped that the
      widespread use of sugammadex in the European Union will provide additional
      information.

PMID- 19384230
TI  - Tattooing and various piercing: anaesthetic considerations.
AB  - PURPOSE OF REVIEW: Body art is increasing since the 1990s. Anaesthesiologists
      would be more and more confronted to patient with tattooing or piercing, or both.
      This review discusses the anaesthetic potential risks and complications observed
      with tattooing and piercing, their management and prevention. RECENT FINDINGS:
      Airway management during anaesthesia is of particular interest with oral jewelry.
      Patients often refuse to remove their piercing for fear of tract closure. There
      are no serious complications reported after epidural puncture through a tattoo,
      although any long-term consequence cannot be discarded yet. Even theoretical
      concerns are more and more debated. SUMMARY: Oral and nasal piercing is of
      particular concern because of the risks of swallowing and aspiration.
      Consequently, patients should be advised to remove piercing before anaesthesia.
      Emergency situations are especially risky and anaesthesiologists should be aware
      of the piercing removal techniques. In case of piercing loss, radiographies and
      fiberoptic endoscopy of the upper airways and digestive tracts should be
      performed to eliminate aspiration or swallowing of the foreign body. Epidurals
      should not be denied to parturients with lumbar tattooing. However, it seems
      still prudent to avoid direct tattoo puncture or when unavoidable, to nick the
      skin prior to inserting the needle through the tattoo.

PMID- 19384231
TI  - Retention of erythrocytes in the spleen: a double-edged process in human malaria.
AB  - PURPOSE OF REVIEW: Splenomegaly is frequent in acute or chronic forms of
      Plasmodium falciparum malaria, and splenectomy is associated with more frequent
      fever and parasitaemia. A novel role for the spleen in malaria is indicated by
      recent epidemiological and experimental data, bringing about a novel paradigm on
      severe malaria pathogenesis. RECENT FINDINGS: In Sudanese children, severe
      malarial anaemia was associated with larger spleen, longer fever duration, and
      lower parasitaemia than cerebral malaria. These findings are consistent with
      evolution toward severe malarial anaemia being linked to the presence of a spleen
      dependent mechanism that is absent or inefficient in cerebral malaria. An
      isolated-perfused human spleen model revealed unexpected retention of numerous
      erythrocytes harbouring young parasite stages (rings), probably through an innate
      mechanical process. SUMMARY: A new paradigm is discussed, whereby the extent of
      erythrocyte retention in the spleen conditions not only haemoglobin concentration
      and spleen size but also the rate of parasite load increase. The prediction is
      that, in nonimmune children, stringent splenic retention of rings and uninfected
      erythrocytes reduces the risk of cerebral malaria (a complication associated with
      high parasite loads) but increases the risk of severe malarial anaemia. This
      hypothesis casts new light on epidemiological, genetic, and experimental studies
      in malaria pathogenesis.

PMID- 19384232
TI  - The effects of neostigmine and glycopyrrolate on skin conductance as a measure of
      pain.
AB  - BACKGROUND AND OBJECTIVE: The number of fluctuations in skin conductance per
      second has been shown to correlate with postoperative pain. In this context, the
      effects of cholinesterase inhibitors and anticholinergic drugs used for the
      reversal of muscle relaxants were investigated. METHODS: Muscle relaxant effects
      were reversed in 30 patients with neostigmine and glycopyrrolate. No reversal
      agents were given to 30 controls. Patients' level of pain was quantified using a
      numeric rating scale (0-10) at several time points in the recovery room. The
      number of fluctuations in skin conductance per second was measured
      simultaneously. RESULTS: The number of fluctuations in skin conductance per
      second was significantly higher in patients with no and severe pain in the
      control compared with the reversal group (no pain 0.19 vs. 0.12; severe pain 0.40
      vs. 0.19). The number of fluctuations in skin conductance per second was less
      sensitive to identify time points with moderate/severe pain in the reversal
      group. CONCLUSION: Skin conductance-based assessment of pain is affected by
      reversal agents.

PMID- 19384233
TI  - One-lung ventilation in a patient with tracheobronchomegaly: a case report and
      literature review.

PMID- 19384234
TI  - Central venous catheter colonization and catheter-related bloodstream infections
      in critically ill patients: a comparison between standard and silver-integrated
      catheters.
AB  - BACKGROUND AND OBJECTIVE: Catheter-related bloodstream infections are one of the
      main complications affecting patients in intensive care units. This prospective,
      randomized, unblinded, controlled study investigated colonization and infection
      rates of standard central venous catheters in comparison with the rates for
      silver-integrated catheters in the intensive care unit. METHODS: Complete data
      were evaluated for 272 catheters inserted into 230 patients (141 standard and 131
      silver-integrated central venous catheters). Patient and catheter characteristics
      were documented for all patients. Positive catheters were detected by semi
      quantitative and quantitative microbiologic techniques. Peripheral blood cultures
      were obtained at the time of catheter removal. RESULTS: There was no significant
      difference in the colonization rates and the colonization per 1000 catheter days
      between the standard and silver-integrated catheters. Using the Kaplan-Meier
      curves (long-rank test), there was a significant difference in the incidence of
      colonization and infections over time between standard and silver-integrated
      catheters (P<0.01 and P<0.05, respectively). Whereas standard catheters were
      first colonized 3 days after the insertion, silver-integrated catheters were
      first colonized 5 days after insertion. CONCLUSION: Silver-integrated central
      venous catheters did not prevent catheter colonization and infections in
      critically ill patients, but there might be a significant difference in the
      incidence of colonization and infections over time between standard polyurethane
      and silver-integrated catheters.

PMID- 19384235
TI  - Perioperative anaesthetic management of mediastinal mass in adults.
AB  - Mediastinal mass syndrome remains an anaesthetic challenge that cannot be
      underestimated. Depending on the localization and the size of the mediastinal
      tumour, the clinical presentation is variable ranging from a complete lack of
      symptoms to severe cardiorespiratory problems. The administration of general
      anaesthesia can be associated with acute intraoperative or postoperative
      cardiorespiratory decompensation that may result in death due to tumour-related
      compression syndromes. The role of the anaesthesiologist, as a part of the
      interdisciplinary treatment team, is to ensure a safe perioperative period.
      However, there is still no structured protocol available for perioperative
      anaesthesiological procedure. The aim of this article is to summarize the genesis
      of and the diagnostic options for mediastinal mass syndrome and to provide a
      solid detailed methodology for its safe perioperative management based on a
      review of the latest literature and our own clinical experiences. Proper
      anaesthetic management of patients with mediastinal mass syndrome begins with an
      assessment of the preoperative status, directed foremost at establishing the
      localization of the tumour and on the basis of the clinical and radiological
      findings, discerning whether any vital mediastinal structures are affected. We
      have found it helpful to assign 'severity grade' (using a three-grade clinical
      classification scale: 'safe', 'uncertain', 'unsafe'), whereby each stage triggers
      appropriate action in terms of staffing and apparatus, such as the provision of
      alternatives for airway management, cardiopulmonary bypass and additional
      specialists. During the preoperative period, we are guided by a 12-point plan
      that also takes into account the special features of transportation into the
      operating theatre and patient monitoring. Tumour compression on the airways or
      the great vessels may create a critical respiratory and/or haemodynamic
      situation, and therefore the standard of intraoperative management includes
      induction of anaesthesia in the operating theatre on an adjustable surgical
      table, the use of short-acting anaesthetics, avoidance of muscle relaxants and
      maintenance of spontaneous respiration. In the case of severe clinical symptoms
      and large mediastinal tumours, we consider it absolutely essential to cannulate
      the femoral vessels preoperatively under local anaesthesia and to provide for the
      availability of cardiopulmonary bypass in the operating theatre, should
      extracorporeal circulation become necessary. The benefits of establishing
      vascular access under local anaesthesia clearly outweigh any associated degree of
      patient discomfort. In the case of patients classified as 'safe' or 'uncertain',
      a preoperative consensus with the surgeons should be reached as to the
      anaesthetic approach and the management of possible complications.

PMID- 19384236
TI  - Relationship between plasma antioxidant concentrations and carotid intima-media
      thickness: the Asymptomatic Carotid Atherosclerotic Disease In Manfredonia Study.
AB  - BACKGROUND: Few studies have examined the relationship among carotid
      atherosclerosis, vascular risk factors, and antioxidant plasma concentrations,
      and those that have reported conflicting results. The aim of this study was to
      assess the relationship between asymptomatic carotid atherosclerosis, as defined
      by carotid intima-media thickness (CIMT), and inflammatory markers, plasma lipids
      and serum antioxidant vitamins. METHODS AND RESULTS: We examined baseline
      characteristics of the 640 participants in the Asymptomatic Carotid
      Atherosclerotic Disease In Manfredonia Study. All participants were asymptomatic
      with respect to carotid artery disease in 2006-2007 and underwent physical
      examination with carotid ultrasound investigation, the collection of medical
      history and laboratory data. Analysis of variance methods were used to examine
      differences between participants by category of CIMT. Of the 640 participants,
      291 did not have evidence of carotid atherosclerosis (CIMT<0.8 mm), 232 were
      found to have some atherosclerosis (0.8 mm< or =CIMT<1.2 mm), and 117 were found
      to have extensive atherosclerosis (CIMT>1.2 mm). Among participants with CIMT> or
      =0.8 mm, body mass index, blood pressures, total cholesterol, LDL cholesterol,
      triglycerides, uric acid, C-reactive protein, and fibrinogen were significantly
      higher, whereas concentrations of vitamin A, vitamin E, lycopene, and beta
      carotene were all significantly lower when compared with participants who did not
      show evidence of carotid atherosclerosis (P<0.001). CONCLUSION: The optimal
      control of hypertension, diabetes, and dyslipidemia, in addition to smoking
      cessation and an adequate intake of antioxidant micronutrients from foods
      represent a key for the prevention of atherosclerotic disease.

PMID- 19384237
TI  - Renal colic as the first symptom of acute renal vein thrombosis, resulting in the
      diagnosis of nephrotic syndrome.
AB  - Renal vein thrombosis is a well-known complication of nephrotic syndrome, but
      rarely its first or only symptom. We describe a 26-year-old patient presenting
      with flank pain suggestive of renal colic. A computed tomography scan showed
      acute renal vein thrombosis, the only sign of a later diagnosed nephrotic
      syndrome. This is a rare presentation of a renal vein thrombosis caused by
      nephrotic syndrome, and easily misdiagnosed as renal calculi especially in young
      and otherwise asymptomatic patients.

PMID- 19384238
TI  - The prevalence of motor delay among HIV infected children living in Cape Town,
      South Africa.
AB  - Children living with HIV often display delayed motor performance owing to HIV
      infection of the central nervous system, the effects of opportunistic infections
      and, indirectly, owing to their social environments. Although these problems have
      been well documented, the impact of the virus on the development of South African
      children is less well known. The aim of this study was to document the motor
      performance of a group of HIV infected children in Cape Town, South Africa. The
      Bayley Scales of Infant Development Second Edition were administered to 51 HIV
      infected children [mean age 15.8 months (SD=7.5, range 6.2-31.7 months)] of whom
      34 were receiving antiretroviral therapy. Their performance was compared with an
      age-matched reference sample (n=35), whose HIV status was unknown. The HIV
      infected sample and the age-matched sample were comparable with regard to
      caregiver's level of education (P=0.42), employment status (P=0.35) and income
      (P=0.28). However, the HIV infected sample had significantly more hospital
      admissions (P<0.01), their caregivers were mostly single (P=0.04) and most lived
      in formal houses (P<0.01). The prevalence of significant motor delay was 66.7% in
      the HIV infected sample compared with 5.7% in the age-matched sample. As
      expected, the performance of the HIV infected sample was significantly poorer
      than the age-matched sample. However, the extent of the delay is a cause of
      concern as so many children presented with significant motor delay. Unexpectedly,
      a significant number of healthy children also displayed delayed performance. It
      is recommended that the developmental performance of HIV infected children be
      monitored over an extended period to determine whether the developmental delay
      can be reduced with treatment. In the interim, there is a need to provide
      stimulation and treatment to the large number of children who are developmentally
      delayed as a result of HIV infection, including those uninfected children in the
      community who are at risk owing to their socio-economic status.

PMID- 19384239
TI  - Systemic sclerosis and aortic valve stenosis: therapeutic implications in two
      cases of aortic valve replacement.
AB  - Cardiac involvement is very frequent and underestimated in systemic sclerosis,
      but few reports have been published on the surgical treatment of patients with
      systemic sclerosis. We describe herein two cases of valve replacement because of
      aortic stenosis.

PMID- 19384240
TI  - Anomalous left coronary artery arising from the right sinus of Valsalva causing
      angina pectoris.
AB  - We present a patient with an anomalous left coronary artery arising from the
      right sinus of Valsalva with effort angina. Diagnosis was made by coronary
      angiography. The course of the proximal segment was assessed with magnetic
      resonance imaging (MRI). An internal mammary artery was successfully grafted with
      symptomatic improvement.

PMID- 19384241
TI  - Pulmonary vein metastasis of a sacral chordoma extending into the left atrial
      cavity.
AB  - Chordomas are rare malignant tumors that rise from notochordal remnants of the
      developing spine. Distant metastases are rare and mostly occur in patients with
      local recurrence. In the case reported, 14 years after radical resection of a
      sacral chordoma, a distant metastasis to the left pulmonary vein with large
      intracardiac mass, location never described before, was diagnosed. No evidence of
      local recurrence was observed. Although the intracardiac tumor part was
      successfully resected, the patient died of heart failure.

PMID- 19384242
TI  - Randomized evaluation of intracoronary nitroprusside vs. adenosine after thrombus
      aspiration during primary percutaneous coronary intervention for the prevention
      of no-reflow in acute myocardial infarction: the REOPEN-AMI study protocol.
AB  - BACKGROUND: Thrombus aspiration improves microvascular obstruction in patients
      with acute myocardial infarction treated by percutaneous coronary intervention.
      However, drugs such as nitroprusside and adenosine have not yet been tested as
      adjuncts to thrombus aspiration. Therefore, we designed a placebo-controlled,
      randomized, open-label, blind-examination, multicenter trial assessing the
      effects of intracoronary nitroprusside or adenosine on microvascular obstruction
      in patients undergoing primary or rescue percutaneous coronary intervention and
      thrombus aspiration. METHODS AND RESULTS: Six hospitals in Italy participate in
      the REOPEN-AMI study. Two hundred and forty consecutive patients with acute
      myocardial infarction undergoing primary or rescue percutaneous coronary
      intervention and thrombus aspiration are randomly allocated 1: 1: 1 to receive
      either intracoronary nitroprusside, adenosine or placebo. The primary end-point
      is the incidence of ST resolution greater than 70% on surface ECG at 90 min after
      the procedure. Secondary end-points are: incidence of angiographic no-reflow
      (thrombolysis in myocardial infarction flow < or =2 or 3 with a myocardial blush
      grade <2); changes of left ventricular volumes at follow-up (at bidimensional
      echocardiography); rate of major adverse cardiac events (cardiac death,
      myocardial infarction, target lesion revascularization and heart failure
      requiring hospitalization). CONCLUSIONS: REOPEN-AMI will provide important data
      on the efficacy and safety of intracoronary nitroprusside and adenosine as an
      adjunctive treatment to percutaneous coronary intervention after thrombus
      aspiration for patients with acute myocardial infarction.

PMID- 19384243
TI  - Corticosteroid side effects and counseling in patients with inflammatory bowel
      disease.

PMID- 19384244
TI  - Intrafamilial spread of Helicobacter pylori infection in Greece.
AB  - GOAL: To find out the role of family members in the Helicobacter pylori infection
      in childhood by investigating the incidence of infection within families of H.
      pylori-infected children. BACKGROUND: H. pylori infection is usually acquired in
      early childhood and possibly family members are the main source of infection.
      STUDY: One hundred consecutive children with upper gastrointestinal symptoms,
      without previous H. pylori eradication treatment were prospectively studied by
      gastroscopy and C-urea breath test. Simultaneously, all family members were
      studied by C-urea breath test regardless of earlier eradication treatment for H.
      pylori infection. The age of children and their parents, socioeconomic status,
      parents' education, and living conditions were recorded. RESULTS: Forty-four
      index symptomatic children were infected by H. pylori. No statistical difference
      was found concerning demographic factors, between H. pylori-positive and H.
      pylori-negative index children except age, which was higher in the H. pylori
      infected children (P=0.009). In all H. pylori-positive and in 71.4% of the
      negative index children, at least 1 more family member was infected (P<0.001),
      always including a parent in the H. pylori-positive, compared with 69.6% in the
      H. pylori-negative group (P<0.001). The percentage of infected siblings, mothers
      and fathers was higher in H. pylori-infected index children (P<0.001, P=0.001,
      and P=0.035, respectively). CONCLUSIONS: The prevalence of H. pylori infection is
      significantly higher among families of infected index children. The presence of
      at least 1 infected family member in all H. pylori-positive index children
      suggests that the family could be the main source of H. pylori infection in
      children.

PMID- 19384245
TI  - Increasing prevalence of erosive esophagitis among Taiwanese aged 40 years and
      above: a comparison between two time periods.
AB  - BACKGROUND: Earlier prevalence studies have reported an increasing trend of
      gastroesophageal reflux disease in Asia, and obesity may be the promoting factor.
      GOALS: This study compared the prevalence of erosive esophagitis and obesity
      status among the same source of subjects in Taiwan between 1995 and 2002. STUDY:
      In the same routine health checkup unit, we recruited 1902 apparently healthy
      adults in 2002 matched by sex and age with 2044 individuals recruited in 1995.
      The prevalence of esophagitis and body mass index between these 2 groups were
      compared. RESULTS: The crude prevalence of esophagitis increased from 5% in 1995
      to 12.6% in 2002 (P<0.0001). Comparing by age stratum, there was an increase of
      esophagitis among subjects aged 40 years and above, with a dose-response
      relationship of adjusted prevalence ratios 2.65 [95% confidence interval (CI):
      1.10, 4.20] in those aged 40 to 49 years, 3.15 (95% CI: 1.51, 4.79) in those aged
      50 to 59 years, and 4.33 (95% CI: 2.56, 6.11) in those aged 60 years and above.
      The prevalence of esophagitis increased in both sexes. BMI was positively
      associated with the presence of esophagitis in women, but the proportion of
      overweight or obesity did not increase in women aged 40 years and above over
      time. CONCLUSIONS: There was a 2.5-fold of increase in prevalence of erosive
      esophagitis among Taiwanese adults from 1995 to 2002, particularly in those aged
      40 years and above. Factors other than obesity seem to contribute to the
      increasing trend of erosive esophagitis in Taiwanese women.

PMID- 19384246
TI  - Thiazolidinediones in NASH. An odd couple meant to be?

PMID- 19384247
TI  - Proton pump inhibitors: a better prescription is needed.

PMID- 19384248
TI  - How much do gastroenterology fellows know about nutrition?
AB  - BACKGROUND: Many people are afflicted with chronic diseases, in which nutrition
      plays a key role. The need for greater nutrition training among physicians,
      particularly gastroenterologists, is becoming increasingly evident. OBJECTIVES:
      To determine the nutritional knowledge and perceived nutrition knowledge of
      gastroenterology fellows. METHODS: Thirty-two gastrointestinal (GI) fellows
      currently enrolled in a GI fellowship program completed a needs assessment
      evaluating perceived nutrition knowledge and interest in the areas of nutrition
      support, assessment, obesity, micro/macronutrients, and nutrition in GI diseases.
      Additionally, an examination evaluating nutrition knowledge specific to
      gastroenterology fellows was administered. RESULTS: Thirty-two GI fellows
      completed the needs assessment. Cronbach alpha of the needs assessment instrument
      was 0.72, indicating satisfactory internal consistency reliability. GI fellows
      perceived themselves to have the least knowledge in obesity and
      micro/macronutrients. They indicated a perceived greater knowledge base in
      nutrition assessment. The mean total test score was 50.04% (SD=7.84%). Fellows
      had the highest score in the subscale of nutrition assessment (80.64%;
      SD=19.05%), which was significantly higher than scores obtained in nutrition
      support (49.45%; SD=11.98%; P<0.05), micro/macronutrients (37.84%; SD=16.94%;
      P<0.05), obesity (40.11%; SD=20.00%; P<0.05), and nutrition in GI diseases
      (65.05%; SD=22.09%; P<0.05). A backward linear regression including hours of
      nutrition education received during GI fellowship, hours of nutrition education
      received during medical school, and year of GI fellowship accounted for 22.7% of
      the variance in test performance (multiple R=0.477). CONCLUSIONS:
      Gastroenterology fellows think their knowledge of nutrition is suboptimal;
      objective evaluation of nutrition knowledge in this cohort confirmed this belief.
      A formal component of nutrition education could be developed in the context of GI
      fellowship education and continuing medical education as necessary.

PMID- 19384249
TI  - International survey of patients with IBS: symptom features and their severity,
      health status, treatments, and risk taking to achieve clinical benefit.
AB  - BACKGROUND: Although clinicians generally make treatment decisions in irritable
      bowel syndrome (IBS) related to the type of symptoms, other factors such as the
      perceived severity and the risks patients are willing to tolerate for effective
      treatment are also important to consider. These factors are not fully understood.
      OBJECTIVE: To describe among patients with IBS their symptoms and severity,
      quality of life and health status, medications taken, and the risk that they
      would take to continue medications for optimal relief. METHODS: Adult patients
      diagnosed with IBS who accessed the websites of the International Foundation for
      Functional GI Disorders or the University of North Carolina Center for Functional
      GI Disorders filled out questionnaires to address the study aims. RESULTS: The
      1966 respondents (83% female, 91% white, 78% US/Canada) reported impaired health
      status: restricting on average 73 days of activity in a year, having poor health
      related quality of life particularly with dietary restrictions, mood disturbance,
      and interference with daily activity, and 35% reported their symptoms as severe
      defined primarily as pain, bowel difficulties, bloating, and eating/dietary
      restrictions). These symptoms were reported in some combination by over 90%, and
      35.1% endorsed all 4 items. To receive a treatment that would make them symptom
      free, patients would give up 25% of their remaining life (average 15 y) and 14%
      would risk a 1/1000 chance of death. Most of the medications being taken were for
      pain relief and 18% were taking narcotics. Complementary and alternative
      treatments were used by 37%. CONCLUSIONS: Patients accessing IBS informational
      websites report moderate-to-severe impairments in health status, and would take
      considerable risk to obtain symptom benefit. There is an unmet need to find
      effective treatments for patients with IBS and regulatory agencies might consider
      raising risk-benefit ratios when approving new medications for IBS.

PMID- 19384250
TI  - Electroconvulsive therapy in early adolescents with schizophrenia spectrum
      disorders.
AB  - Electroconvulsive therapy is scarcely used in adolescents with diagnoses of
      schizophrenia, although it has been reported as an effective and safe treatment
      in the previous literature. We present 3 cases of early adolescent patients with
      schizophrenia who were treated with electroconvulsive therapy without adverse
      effects.

PMID- 19384251
TI  - Relative ineffectiveness of ultrabrief right unilateral versus bilateral
      electroconvulsive therapy in depression.
AB  - OBJECTIVE: Bilateral (BL) electrode placement delivered at 2.5 times the initial
      seizure threshold (ST; 2.5 x ST) is the gold standard method for seizure delivery
      during electroconvulsive therapy (ECT). However, there is a growing interest in
      using a high dose (6 x ST) with ultrabrief right unilateral (UB-RUL) electrode
      placement to reduce the incidence of possible short-term memory problems
      associated with BL ECT. Although studies have found UB-RUL ECT to have similar
      effectiveness to BL ECT, the objective of this study was to determine potential
      differences in efficiency (ie, the number of treatments needed to reach
      remission). METHODS: Electroconvulsive therapeutic data for 56 patients with
      depression treated during 2006 and 2007 were analyzed via retrospective chart
      review. A total of 26 patients were started on UB-RUL ECT, whereas 30 patients
      were started on brief pulse BL ECT. RESULTS: The patients started on high-dose UB
      RUL ECT required significantly more treatments than the patients started on BL
      ECT (9.4 [3.3] vs 7.7 [2.8] treatments). Of the 26 patients started on UB-RUL
      ECT, 12 (46%) experienced a lack of effectiveness and/or insufficient seizure
      induction and were thus switched to BL ECT; the 8 patients switched because of
      lack of effectiveness received a mean (SD) of 12.2 (2.9) treatments, whereas the
      4 patients switched because of insufficient seizure induction received a mean
      (SD) of 11.3 (3.6) treatments. CONCLUSIONS: These findings add to an emerging
      story of reduced efficiency of UB-RUL versus BL electrode placement for an index
      course of ECT for the treatment of depression.

PMID- 19384252
TI  - Acute and maintenance electroconvulsive therapy for treatment of severely
      disabling obsessive-compulsive symptoms in a patient with Asperger syndrome.
AB  - We report successful treatment with electroconvulsive therapy of a comorbid
      condition including severe obsessive-compulsive symptoms and hypochondriacal
      delusions in a 38-year-old man with Asperger syndrome. His condition deteriorated
      into a severely disabled chronic state that was refractory to different
      pharmacological and psychological treatments but was completely reversed after
      electroconvulsive therapy. Although typical obsessive-compulsive symptoms were
      predominant, the case also exhibits differences compared with regular obsessive
      compulsive disorder regarding onset and course that are discussed in the report.

PMID- 19384253
TI  - Cardiac rhythm disturbance in a depressed patient after implantation with a vagus
      nerve stimulator.
AB  - A 52-year-old woman with a long-standing history of treatment-resistant
      depression failed multiple courses of electroconvulsive therapy and various
      trials of antidepressant medications. As a result, the patient was deemed a good
      candidate for vagus nerve stimulation (VNS) therapy and underwent VNS insertion
      in May 2006. However, in December 2007, she began to experience recurrent falls
      and was referred to a cardiologist for a syncope evaluation. During a portable 30
      day cardiac event recording, she was noted to have intermittent second- and third
      degree heart block with ventricular standstill, which was felt by her
      cardiologist to be associated with VNS stimulation. We believe this to be the
      first reported case of heart block related to VNS in a depressed patient.

PMID- 19384255
TI  - Error positivity is related to attentional control of task switching.
AB  - This study aimed to investigate the relationship between attentional control and
      action monitoring in a task-switching paradigm by examining the error-related
      negativity and positivity, components of event-related potentials that reflect
      action monitoring, including error detection. This study was designed with both a
      task-switching condition and a single-task condition and the results were
      compared between the two conditions. Error-related positivity amplitude decreased
      in the task-switching condition, whereas error-related negativity amplitude did
      not change in either condition. The results therefore support the notion that the
      two error-related components represent different aspects of action monitoring,
      including error detection.

PMID- 19384254
TI  - Gender differences in osteoarthritis.

PMID- 19384258
TI  - What do we mean by "leadership"?

PMID- 19384256
TI  - Neural correlates of size illusions: an event-related potential study.
AB  - The aim of this study was to investigate the neural correlates of size illusions.
      Participants were presented with a sphere of a fixed angular size positioned (i)
      at either a far or close position within a three-dimensional virtual scene or
      (ii) at either an upper or lower screen position on a plain gray background. The
      visual-evoked potentials were recorded while participants were required to fixate
      on and attend to the sphere. The results showed that the amplitude of visual P2
      component was affected by sphere position in the three-dimensional scene
      condition only, suggesting that the activity level of the primary visual cortex
      was modulated by the size illusion at later stages of visual processing.

PMID- 19384259
TI  - Soft contact lens disinfection solution efficacy: clinical Fusarium isolates vs.
      ATCC 36031.
AB  - PURPOSE: To compare the disinfecting efficacy of five soft contact lens
      multipurpose disinfection solutions (MPDS) against Fusarium solani clinical
      isolates and the ISO standard ATCC 36031 strain. METHODS: Three commercially
      available and two recalled MPDS were tested using the ISO/CD 14,729 stand-alone
      test for contact lens care products against 10 ocular isolates of F. solani and
      the ATCC 36031 strain. The effect of filtering the fungal suspension before
      incubating in MPDS was also tested. An average log reduction in colony forming
      units at the manufacturer's minimum recommended disinfection time was determined
      and compared with criteria for stand-alone disinfection products for each MPDS
      against each strain. RESULTS: No difference between filtered and unfiltered
      fungal suspensions was observed for the ISO standard, whereas in one MPDS the
      representative clinical isolate showed significantly increased resistance when
      unfiltered. All but one solution met the stand-alone criteria of 1.0-log
      reduction of colony forming units against the recommended ISO standard strain
      ATCC 36031. However, there was wide variation in the ability of MPDS to meet the
      ISO disinfection criteria when tested against clinical isolates. Among the
      commercially available MPDS, the two polyquaternium-based solutions showed a
      higher disinfecting efficacy than the biguanide-based solution. The two recalled
      solutions showed a lower disinfecting efficacy than the polyquaternium-based
      solutions. Further, the clinical isolates were significantly more resistant to
      disinfection than was the recommended ISO strain. CONCLUSIONS: The effect of
      filtering the fungal suspension to remove hyphae seems to be relevant in the
      clinical isolate tested, but not in the ISO strain. Clinical isolates were
      significantly more resistant to disinfection than the recommended ISO strain in
      the presence of both the commercially available and the recalled MPDS. The use of
      clinical isolates in stand-alone disinfection testing is indicated. Because there
      were significant differences in increased resistance exhibited by clinical
      isolates and in a mixed (unfiltered) culture the use of a single laboratory
      strain may be insufficient to provide assurance that the disinfection solution
      will be effective against clinical isolates.

PMID- 19384260
TI  - Seasonality of respiratory viral identification varies with age and Aboriginality
      in metropolitan Western Australia.
AB  - BACKGROUND: Viral respiratory infections are a major cause of pediatric illness.
      It is not known whether seasonality of viruses differs between Aboriginal and non
      Aboriginal children of varying ages. METHODS: We extracted data on respiratory
      syncytial virus (RSV), influenza viruses A and B, parainfluenza virus types 1, 2,
      and 3 and adenovirus identified through cell culture or direct immunofluorescence
      between 1997 and 2005 from nasopharyngeal or throat specimens at Western
      Australia's only pediatric hospital. We used harmonic analysis in generalized
      linear models to examine the variations in seasonality of these viruses with
      Aboriginality and age. RESULTS: A respiratory virus was identified in 32% of 32
      741 specimens. RSV (18.6%), influenza virus A (5.1%), and parainfluenza virus 3
      (4.0%) were most common. The median age at time of identification was lower in
      Aboriginal children than non-Aboriginal for all viruses except RSV. Seasonality
      differed between all viruses and varied with age for RSV, influenza viruses and
      adenovirus. Influenza viruses A and B activity peaked earlier in Aboriginal than
      non-Aboriginal children during 1997, 1998, and 2002. CONCLUSIONS: All viruses
      showed distinct seasonality. Variability with age and different seasonal patterns
      for influenza viruses in Aboriginal children compared with non-Aboriginal
      children has to be taken into account when identifying target groups and timing
      for vaccination and other interventions.

PMID- 19384263
TI  - Immunogenicity and tolerability in infants of a New Zealand epidemic strain
      meningococcal B outer membrane vesicle vaccine.
AB  - BACKGROUND: An outer membrane vesicle meningococcal vaccine (MeNZB), was
      developed for the New Zealand epidemic strain of Neisseria meningitidis B:4:P1.7
      2,4. METHODS: A phase II, randomized, observer blind, controlled study evaluating
      the safety, reactogenicity, and immunogenicity of MeNZB administered with routine
      New Zealand immunizations at 6 weeks, 3 months, and 5 months of age (n = 375).
      Group 1 (n = 250) received 25 mug MeNZB and routine immunizations with a fourth
      MeNZB dose given at 10 months (n = 51). Group 2 (n = 125) received routine
      immunizations only. Sero-response was a > or =4-fold rise in vaccine strain serum
      bactericidal antibody titer compared with baseline or a titer of at least 1:8 for
      baselines <1:4. Reactogenicity was monitored for 7 days after vaccination.
      RESULTS: Sero-response in Group 1 was achieved in 53% (95% Confidence interval
      [CI]: 46-59, n = 239) and 69% (95% CI: 54-80, n = 45) with geometric mean
      antibody titers of 9 (95% CI: 7-10) and 22 (95% CI: 12-39) after the third and
      fourth doses, respectively. No negative interference by MeNZB on routine
      immunizations was detected. There were no serious adverse events judged to be
      vaccine related. CONCLUSIONS: In this group of New Zealand infants, 4 MeNZB doses
      were required to demonstrate titers comparable with those achieved after 3 doses
      in older children. MeNZB was safe when used concomitantly with routine New
      Zealand immunizations to 5 months of age.

PMID- 19384264
TI  - CYP3A5*1/*3 genotype influences the blood concentration of tacrolimus in response
      to metabolic inhibition by ketoconazole.
AB  - OBJECTIVES: Ketoconazole retards metabolic degradation of tacrolimus through its
      effect on the cytochrome P-450 enzyme system and allows reduction in treatment
      costs. Enzyme activity is determined by a single nucleotide polymorphism (*1/*3)
      in the CYP3A5 gene. METHODS: We prospectively investigated the impact of this
      polymorphism on tacrolimus concentration in a cohort of 79 renal transplant
      recipients on ketoconazole. Genotyping was carried out by using polymerase chain
      reaction-restriction fragment length polymorphism technique. Dose-adjusted trough
      level (C0) was calculated at baseline and at 3, 7, 15, 30, and 60 days. RESULTS:
      The baseline C0 was significantly lower in those with at least one *1 allele
      [44.95+/-14.12 vs. 63.43+/-14.72 (ng/ml)/(mg/kg/day), P<0.0001]. After starting
      ketoconazole in all genotypes, dose-normalized C0 increased and the cost of
      therapy decreased. Compared with baseline, the magnitude of increase was 112% and
      79% in those without and with *1 allele, respectively (P<0.001). The cost savings
      were 32% and 39% in mycophenolate mofetil-treated and 47% and 61% in azathioprine
      treated patients who were with and without one *1 allele, respectively.
      CONCLUSION: We show that the CYP3A5*1/*3 polymorphism is an important determinant
      of the response to inhibition of tacrolimus metabolism by ketoconazole, with a
      30% greater inhibition in those lacking *1 allele. This finding will allow better
      dose adjustment and minimize exposure to subtherapeutic or toxic concentrations.

PMID- 19384265
TI  - The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine
      lowering and migraine disability.
AB  - BACKGROUND: Migraine is a prevalent and debilitating disease that may, in part,
      arise because of disruption in neurovascular endothelia caused by elevated
      homocysteine. This study examined the homocysteine-lowering effects of vitamin
      supplementation on migraine disability, frequency and severity and whether
      MTHFRC677T genotype influenced treatment response. METHODS: This was a
      randomized, double-blind placebo, controlled trial of 6 months of daily vitamin
      supplementation (i.e. 2 mg of folic acid, 25 mg vitamin B6, and 400 microg of
      vitamin B12) in 52 patients diagnosed with migraine with aura. FINDINGS: Vitamin
      supplementation reduced homocysteine by 39% (approximately 4 mumol/l) compared
      with baseline, a reduction that was greater then placebo (P=0.001). Vitamin
      supplementation also reduced the prevalence of migraine disability from 60% at
      baseline to 30% after 6 months (P=0.01), whereas no reduction was observed for
      the placebo group (P>0.1). Headache frequency and pain severity were also reduced
      (P<0.05), whereas there was no reduction in the placebo group (P>0.1). In this
      patient group the treatment effect on both homocysteine levels and migraine
      disability was associated with MTHFRC677T genotype whereby carriers of the C
      allele experienced a greater response compared with TT genotypes (P<0.05).
      INTERPRETATION: This study provides some early evidence that lowering
      homocysteine through vitamin supplementation reduces migraine disability in a
      subgroup of patients. Larger trials are now warranted to establish whether
      vitamin therapy is a safe, inexpensive and effective prophylactic option for
      treatment of migraine and whether efficacy is dependant on MTHFRC677T genotype.

PMID- 19384267
TI  - Evodiamine stabilizes topoisomerase I-DNA cleavable complex to inhibit
      topoisomerase I activity.
AB  - Evodiamine (EVO), an alkaloidal compound isolated from Evodia rutaecarpa (Juss.),
      has been reported to affect many physiological functions. Topoisomerase
      inhibitors have been developed in a variety of clinical applications. In the
      present study, we report the topoisomerase I (TopI) inhibitory activity of EVO,
      which may have properties that lead to improved therapeutic benefits. EVO is able
      to inhibit supercoiled plasmid DNA relaxation catalyzed by TopI. Upon treatment 0
      10 microM EVO TopI was depleted in MCF-7 breast cancer cells in a concentration
      dependent and time-dependent manner in 0-120 min. A K-SDS precipitation assay was
      performed to measure the extent of Top I-trapped chromosomal DNA. The ability of
      EVO to cause the formation of a TopI-DNA complex increased in a concentration
      dependent manner, in that the DNA trapped increased by 24.2% in cells treated
      with 30 microM. The results suggest that EVO inhibits TopI by stabilizing the
      enzyme and DNA covalent complex.

PMID- 19384268
TI  - The shorter the better: reducing fixed primer regions of oligonucleotide
      libraries for aptamer selection.
AB  - Oligonucleotide aptamers are highly structured DNA or RNA molecules, or modified
      versions thereof, that can bind to targets with specific affinities comparable to
      antibodies. They are identified through an in vitro selection process termed
      SELEX (Systematic Evolution of Ligands by EXponential enrichment) to recognize a
      wide variety of targets, from small molecules to proteins, and from cultured
      cells to whole organisms. Aptamers possess a number of desirable properties, such
      as ease of synthesis, stability, robustness, and lack of immunogenicity. Standard
      SELEX libraries require two primers, one on each side of a central random domain,
      to amplify the target-bound sequences via PCR or RT-PCR. However, these primer
      sequences cause non-specific binding by their nature, and have been reported to
      lead to large numbers of false-positive binding sequences, or to interfere with
      binding of sequences within the random regions. This review is focused on methods
      which have been developed to eliminate fixed primer interference during the SELEX
      process.

PMID- 19384269
TI  - Syntheses, spectroscopic and AFM characterization of some manganese porphyrins
      and their hybrid silica nanomaterials.
AB  - The present work is concerned with the manganese complexes of 5,10,15,20
      tetraphenylporphyrin and of 5,10,15,20-tetra(3-hydroxyphenyl)porphyrin, which
      were prepared by metallation of the corresponding porphyrin ligands, and the
      study of their spectroscopic and photophysical behavior under strongly acidic and
      alkaline conditions. The second objective was to obtain and study some new hybrid
      materials, with special optoelectronic and surface properties, by impregnation of
      silica gels obtained by one step acid and by two steps acid-base catalysis with
      these Mn-porphyrins. The resulting nanomaterials exhibited interesting
      bathochromic and hyperchromic effects of their second band in the emission
      spectra in comparison with the Mn-porphyrins and also they have distinct
      orientation of the aggregates on surfaces, as shown by AFM images, making them
      useful for applications in medicine, formulation of sensors and for environmental
      friendly catalysts for photodegradation of organic compounds.

PMID- 19384271
TI  - A new insecticidal sesquiterpene ester from Celastrus angulatus.
AB  - A new sesquiterpene polyol ester with a beta-dihydroagarofuran skeleton, NW37
      (1), and three known compounds NW13 (2), NW16 (3) and NW35 (4) were isolated by
      bioassay-guided fractionation from the highly polar MeOH extracts of the root
      bark of Celastrus angulatus. Their chemical structures were elucidated mainly by
      analyses of MS and NMR spectral data. The insecticidal activity of compound 1
      against 4th instar Mythimna separata larvae with a KD(50) value of 252.3 microg
      g(-1) was demonstrated.

PMID- 19384270
TI  - Antimalarial and cytotoxic phenolic compounds from Cratoxylum maingayi and
      Cratoxylum cochinchinense.
AB  - Nine phenolic compounds isolated from Cratoxylum maingayi and C. cochinchinense
      were evaluated for anti-malarial activity against Plasmodium falciparum, and for
      cytotoxic activity against the NCI-H187 (human small cell lung cancer) cancer
      cell line. Formoxanthone C (3) was found to be the most active against the NCI
      H187 cancer cell line, with an IC(50) of 0.22 microg/mL, while vismione B (7) had
      the highest activity against Plasmodium falciparum, with an IC(50) of 0.66
      microg/mL.

PMID- 19384272
TI  - Molecular docking studies and anti-enzymatic activities of Thai mango seed kernel
      extract against snake venoms.
AB  - The ethanolic extract from seed kernels of Thai mango (MSKE) (Mangifera indica L.
      cv. 'Fahlun') (Anacardiaceae) and its major phenolic principle (pentagalloyl
      glucopyranose) exhibited dose-dependent inhibitory effects on enzymatic
      activities of phospholipase A(2) (PLA(2)), hyaluronidase and L-amino acid oxidase
      (LAAO) of Calloselasma rhodostoma (CR) and Naja naja kaouthia (NK)venoms by in
      vitro tests. The anti-hemorrhagic and anti-dermonecrotic activities of MSKE
      against both venoms were clearly supported by in vivo tests. Molecular docking
      studies indicated that the phenolic molecules of the MSKE could selectively bind
      to the active sites or their proximity, or modify conserved residues that are
      critical for the catalysis of PLA(2), and selectively bind to the LAAO binding
      pocket of both CR and NK venoms and thereby inhibit their enzymatic activities.
      The results imply a potential use of MSKE against snake venoms.

PMID- 19384273
TI  - Ultrasound promoted synthesis of bis(substituted pyrazol-4-ylcarbonyl)
      substituted thioureas.
AB  - A series of novel bis(substituted pyrazol-4-ylcarbonyl)-substituted thioureas
      have been synthesized by the reactions of substituted pyrazol-4-ylcarbonyl
      isothiocyanates with different diamines under ultrasound irradiation and
      classical heating method at 20-25 degrees C. In general, substantial improvement
      in rates and modest yields increases were observed when reactions were carried
      out under sonication, compared with the classical heating method. The structures
      of these compounds have been elucidated by elemental and spectral (IR, (1)H-NMR)
      analysis.

PMID- 19384274
TI  - Synthesis of new naphtho[2,3-f]quinoxaline-2,7,12(1H)-trione and anthra-9,10
      quinone dyes from furan-2,3-diones.
AB  - Novel naphtho[2,3-f]quinoxaline-2,7,12(1H)-trione and anthra-9,10-quinone dyes
      were synthesized in good yield from furan-2,3-diones using 1,2-diaminoanthra-9,10
      quinone and 1,4-diaminoanthra-9,10-quinone. The chromophores were characterized
      by molecular spectroscopy methods.

PMID- 19384275
TI  - Chemical composition and biological activities of essential oil from Salvia
      sclarea plants regenerated in vitro.
AB  - The essential oils obtained by hydrodistillation of dried aerial parts of Salvia
      sclarea L. plants, regenerated in vitro and reproduced from seeds, were analyzed
      by GC and GC-MS. The oils from in vitro and in vivo plants were compared in
      respect to their chemical composition as well as antimicrobial and cytotoxic
      activities. The chemical profiles of both oils were very similar, although the
      yield of essential oil from in vitro plants was lower (0.1%, v/w) than the oil
      yield isolated from in vivo S. sclarea plants (0.2%, v/w). Both oils showed
      antimicrobial and cytotoxic activity. The oil from in vitro regenerated plants of
      S. sclarea exhibited stronger cytotoxic action against NALM-6 cell lines in
      comparison with the essential oil from in vivo plants.

PMID- 19384276
TI  - QSAR studies on N-aryl derivative activity towards Alzheimer's disease.
AB  - A Quantitative Structure Activity Relationship (QSAR) study has been an attempted
      on a series of 88 N-aryl derivatives which display varied inhibitory activity
      towards both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE),
      targets in Alzheimer's drug discovery. QSAR models were derived for 53 and 61
      compounds for each target, respectively, with the aid of genetic function
      approximation (GFA) technique using topological, molecular shape, electronic and
      structural descriptors. The predictive ability of the QSAR model was evaluated
      using a test set of 26 compounds for AChE (r(2)(pred) = 0.857), (q(2)= 0.803) and
      20 compounds for BChE (r(2)(pred)= 0.882), (q(2)= 0.857). The QSAR models point
      out that AlogP98, Wiener, Kappa-1-AM, Dipole-Mag, and CHI-1 are the important
      descriptors effectively describing the bioactivity of the compounds.

PMID- 19384277
TI  - Polyphenolic profile and bioactivity study of Oenothera speciosa Nutt. aerial
      parts.
AB  - Two new flavonol glycosides, myricetin 4'-O-alpha-L-rhamnopyranoside (1) and
      quercetin 3'-O-alpha-L-rhamnopyranoside (2), together with a novel biflavonol
      compound, speciin (3), as well as eleven phenolic metabolites, namely myricitrin
      (4), europetin 3-O-alpha-L-(1)C(4)-rhamnopyranoside (5), quercitrin (6), hyperin
      (7), rhamnetin 3-O-beta-galacto-pyranoside (8), caffeic acid (9), caffeic acid
      methyl ester (10), chlorogenic acid (11), chlorogenic acid methyl ester (12),
      gallic acid (13) and gallic acid methyl ester (14), were identified from the 80 %
      methanol extract of the aerial parts (leaves and stems) of Oenothera speciosa
      Nutt. (Onagraceae). In addition myricetin (15), quercetin (16) and ellagic acid
      (17) were identified from the chloroform extract. The structures were established
      depending on their chemical and physical analyses (UV, HR-ESIMS, 1D and 2D NMR).
      It was found that 80 % aqueous methanol extract of O. speciosa is non-toxic to
      mice up to 5 g kg(-1)b wt. The investigated extract exhibited significant
      antihyperglycaemic and anti-inflammatory activities in a dose dependant manner.
      Also, the 80 % methanol extract, myricitrin(4) and hyperin(7) showed potent
      antioxidant activity in vitro using 1,1-diphenyl 2-picryl hydrazyl (DPPH) radical
      assay.

PMID- 19384278
TI  - An efficient one-pot three-component synthesis of fused 1,4-dihydropyridines
      using HY-zeolite.
AB  - A facile and convenient protocol was developed for the fast (2.5-3.5 h) and high
      yielding (70-90%) synthesis of fused 1,4-dihydropyridines from dimedone in the
      presence of HY-zeolite as an efficient recyclable heterogeneous catalyst.

PMID- 19384279
TI  - Maize arabinoxylan gels as protein delivery matrices.
AB  - The laccase induced gelation of maize bran arabinoxylans at 2.5% (w/v) in the
      presence of insulin or beta-lactoglobulin at 0.1% (w/v) was investigated. Insulin
      and beta-lacto-globulin did not modify either the gel elasticity (9 Pa) or the
      cross-links content (0.03 and 0.015 microg di- and triferulic acids/mg
      arabinoxylan, respectively). The protein release capability of the gel was also
      investigated. The rate of protein release from gels was dependent on the protein
      molecular weight. The apparent diffusion coefficient was 0.99 x 10(-7) and 0.79 x
      10(-7) cm(2)/s for insulin (5 kDa) and beta-lactoglobulin (18 kDa), respectively.
      The results suggest that maize bran arabinoxylan gels can be potential candidates
      for the controlled release of proteins.

PMID- 19384280
TI  - Synthesis of novel hybrid molecules from precursors with known antiparasitic
      activity.
AB  - Three novel new compounds derived from antiparasitic precursors have been
      synthesized and tested for their antiamoebic and antigiardial activities. The
      condensation of 2-(2-methyl-5-1H-nitroimidazolyl)ethylamine (6) with 5-nitro-2
      furylacrylic acid (7) gave 3-(5-nitrofuran-2-yl)-N-[2-(5-nitroimidazol-1
      yl)ethyl]acrylamide (8). Condensation of 7 with 7-chloro-4-(piperazin-1
      yl)quinoline (9) afforded 1-[4-(7-chloroquinolin-4-yl)piperazin-1-yl)-3-(5
      nitrofuran-2-yl)propenone as a mixture of two isomers; 10-a (the E-isomer) and 10
      b (the Z-isomer). In addition, the reaction of 9 with 1-(2-bromoethyl)-2-methyl-5
      nitroimidazole (11) in the presence of K(2)CO(3) and NaI yielded 7-chloro-4-(4-[2
      (5-nitroimidazol-1-yl)ethyl]-piprazin-1-yl)quinoline (12). On the basis of
      preliminary screening data for these new compounds, compound 12 exhibited potent
      lethal activities against Entamoeba histolytica and Giardia intestinalis; its
      IC(50) (about 1 microM) was lower, at least by a factor of five, compared to the
      standard drug, metronidazole. In addition, the IC(50) of compound 12 against the
      tested parasites is 600 times below that against Hep-2 and Vero cells. Compounds
      8 and 10-a also exhibited potent or moderate antiamoebic and antigiardial
      activities with IC(50 values) of about 5.5 microM, and 140 microM, respectively,
      against the tested parasites. These two hybrid molecules, 8, 10-a, were also non
      cytotoxic at the lethal concentrations against the parasites.

PMID- 19384281
TI  - Synthesis and molecular descriptor characterization of novel 4-hydroxy-chromene-2
      one derivatives as antimicrobial agents.
AB  - Several novel 4-hydroxy-chromene-2-one derivatives 2b-16b were easily prepared
      through condensation reactions with microwave heating and characterized by
      elemental analysis, IR, (1)H-NMR and mass spectrometry. Geometry optimization of
      these compounds was executed by PM3, PM5 and Minimize Energy methods to describe
      them via molecular descriptors. The antimicrobial activity of the synthesized
      compounds was evaluated against different microbial strains using two different
      methods: the diffusion method and the micro-dilution method. All data indicated
      that the products possess antimicrobial activity which depends on the nature of
      substituent attached to the benzopyran moiety. In general, after 24 h the MIC
      values of most tested coumarins was 0.13 mg/mL, but compounds 1 and 6b displayed
      the strongest antimicrobial activity on the tested cultures of bacteria after 48
      h. Compound 13b has the strongest growth inhibitory potential on fungus C.
      albicans, tested by diffusion method,with an inhibition zone of 30-37 mm at a
      concentration of 150 microg/mL. The conclusion of this experiment is that the
      synthesized compounds have varied and different influence on different classes of
      bacteria and the fungus C. albicans.

PMID- 19384282
TI  - Comparative molecular docking of antitrypanosomal natural products into multiple
      Trypanosoma brucei drug targets.
AB  - Antitrypanosomal natural products with different structural motifs previously
      shown to have growth inhibitory activity against Trypanosoma brucei were docked
      into validated drug targets of the parasite, which include trypanothione
      reductase, rhodesain, farnesyl diphosphate synthase, and triosephosphate
      isomerase. The in-silico calculations predicted that lowest energy docked poses
      of a number of the compounds can interact with catalysis-dependent residues, thus
      making them possible catalytic inhibitors and of course physiologically active.
      Compounds that possess a number of hydrogen-bond-accepting and/or -donating
      groups like phenolics and quinones show extensive interactions with the targets.
      Compounds like cissampeloflavone, 3-geranylemodin and ningpogenin thus offer
      profound promise.

PMID- 19384283
TI  - Determination of proton relaxivities of Mn(II), Cu(II) and Cr(III) added to
      solutions of serum proteins.
AB  - Relaxometric studies are still of scientific interest due to their use in
      medicine and biology. In this study, proton T(1) and T(2) relaxivities of Mn(II),
      Cu(II) and Cr(III) in water were determined in the presence and absence of
      various proteins (albumin, alpha-globulin, gamma-globulin, lysozyme, fibrinogen).
      The 1/T(1) and 1/T(2) in all solutions are linearly proportional to the
      concentration of the paramagnetic ions. Mn(II) has the great influence to alter
      relaxations in all protein solutions, while Cu(II) and Cr(III) have a poor
      influence on the relaxations. In addition, Mn(II) and Cu(II) are bound to each
      protein, but Cr(III) is not bound to any protein.

PMID- 19384284
TI  - Pseudo-cyclic face-to-face rigid structure caused by the intramolecular ion pair
      effect.
AB  - Six 3-methylpyridine zwitterions and six quinoline zwitterions were synthesized
      through the reaction of 4-hydroxycoumarins, p-benzoquinone and the corresponding
      N-aromatics. The novel pseudo-cyclic face-to-face rigid structure of the
      zwitterion was elucidated by (1)H-NMR at different temperatures, and assumed to
      be caused by both the intramolecular ion pair attraction and the steric
      interaction.

PMID- 19384285
TI  - Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals
      considerations and efficacy; a review article.
AB  - Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) which have
      a combined incidence of 5-8/100,000 population, represent the most common primary
      central nervous system tumors. The treatment outcomes even with aggressive
      approach including surgery, radiation therapy and chemotherapy are dismal with
      median reported survival is less than 1 year. Temozolomide is a new drug which
      has shown promise in treating malignant gliomas and other difficult-to-treat
      tumors. This drug is a per os (p.o) imidazotetrazine second-generation alkylating
      agent which represents the leading compound in a new class of chemotherapeutic
      agents that enter the cerebrospinal fluid and do not require hepatic metabolism
      for activation. The efficacy of temozolomide was tested in vitro studies and has
      demonstrated schedule-dependent antitumor activity against highly resistant
      malignancies, including high-grade glioma (HGG). In addition, in clinical
      studies, temozolomide consistently demonstrates reproducible linear
      pharmacokinetics with approximately 100% p.o. bioavailability, noncumulative
      minimal myelosuppression that is rapidly reversible, and activity against a
      variety of solid tumors in both children and adults. Moreover, preclinical
      studies have evaluated the combination of temozolomide with other alkylating
      agents and inhibitors of the DNA repair protein O(6)-alkylguanine
      alkyltransferase to overcome resistance to chemotherapy in malignant glioma and
      malignant metastatic melanoma. At the present time temozolomide is approved in
      the United States for the treatment of adult patients with refractory anaplastic
      astrocytoma and, in the European Union, for treatment of glioblastoma multiforme
      showing progression or recurrence after standard therapy. Temozolomide's
      characteristics which make it a candidate for a wide range of clinical testing to
      evaluate the potential of combination treatments in different tumor types are its
      predictable bioavailability and minimal toxicity. An overview of the mechanism of
      action of temozolomide and a summary of results from more important randomized
      controlled clinical trials in high grade gliomas are presented here.

PMID- 19384286
TI  - Trinor-cycloartane glycosides from the rhizomes of Cimicifuga foetida.
AB  - Three new trinor-cycloartane glycosides, 15alpha-hydroxy-16-dehydroxy-16(24)-en
      foetidinol-3-O-beta-D-xylopyranoside (1), 28-hydroxy-foetidinol-3-O-beta-D
      xylopyranoside (2) and foetidinol-3-O-beta-D-xylopyranosyl-(1"-->3')-beta-D
      xylopyranoside (3) together with the known compound foetidinol-3-O-beta-D
      xylopyranoside (4) were isolated from the n-BuOH fraction of the roots of
      Cimicifuga foetida. Their structures were elucidated on the basis of
      spectroscopic and chemical reaction data.

PMID- 19384287
TI  - Essential oil composition of Artemisia herba-alba from southern Tunisia.
AB  - The composition of the essential oil hydrodistilled from the aerial parts of 18
      individual Artemisia herba-alba Asso. plants collected in southern Tunisia was
      determined by GC and GCMS analysis. The oil yield varied between 0.68% v/w and
      1.93% v/w. One hundred components were identified, 21 of of which are reported
      for the first time in Artemisia herba-alba oil. The oil contained 10 components
      with percentages higher than 10%. The main components were cineole, thujones,
      chrysanthenone, camphor, borneol, chrysanthenyl acetate, sabinyl acetate, davana
      ethers and davanone. Twelve samples had monoterpenes as major components, three
      had sesquiterpenes as major components and the last three samples had
      approximately the same percentage of monoterpenes and sesquiterpenes. The
      chemical compositions revealed that ten samples had compositions similar to those
      of other Artemisia herba-alba essential oils analyzed in other countries. The
      remaining eight samples had an original chemical composition.

PMID- 19384288
TI  - Synthesis of gamma-nitro aliphatic methyl esters via Michael additions promoted
      by microwave irradiation.
AB  - A simple and efficient protocol has been developed for the direct synthesis of
      gamma-nitrobutyric acid methyl esters under microwave irradiation. This
      methodology reduces reaction times from days to minutes, compared to conventional
      conditions. Additionally, these conditions increased yields and provided cleaner
      reactions.

PMID- 19384289
TI  - Preparation of benzothiazole-substituted carbosilane dendrimers up to the 7th
      generation.
AB  - Carbosilane dendrimers with 2-(2-phenyloxy)benzothiazole groups on the periphery
      were prepared from the 1(st) to the 7(th) generation. All dendrimers were
      characterized by (1)H- and (13)C-NMR, elemental analysis, MALDI TOF MS, GPC, and
      PL (photoluminescence) spectroscopy. Characteristic PDI (Polydisperse Index)
      values of the peaks corresponding to the respective dendrimers in the GPC data is
      in very narrow range of 1.00-1.04. All PL spectra show a blue-shift increasing
      with generation from the 1(st) to the 7(th).

PMID- 19384290
TI  - Systemic correction of storage disease in MPS I NOD/SCID mice using the sleeping
      beauty transposon system.
AB  - The Sleeping Beauty (SB) transposon system is a nonviral vector that directs
      transgene integration into vertebrate genomes. We hydrodynamically delivered SB
      transposon plasmids encoding human alpha-L-iduronidase (hIDUA) at two DNA doses,
      with and without an SB transposase gene, to NOD.129(B6)-Prkdc(scid)
      IDUA(tm1Clk)/J mice. In transposon-treated, nonobese diabetic/severe combined
      immunodeficiency (NOD/SCID) mice with mucopolysaccharidosis type I (MPS I),
      plasma IDUA persisted for 18 weeks at levels up to several hundred-fold wild-type
      (WT) activity, depending on DNA dose and gender. IDUA activity was present in all
      examined somatic organs, as well as in the brain, and correlated with both
      glycosaminoglycan (GAG) reduction in these organs and level of expression in the
      liver, the target of transposon delivery. IDUA activity was higher in the treated
      males than in females. In females, omission of transposase source resulted in
      significantly lower IDUA levels and incomplete GAG reduction in some organs,
      confirming the positive effect of transposition on long-term IDUA expression and
      correction of the disease. The SB transposon system proved efficacious in
      correcting several clinical manifestations of MPS I in mice, including thickening
      of the zygomatic arch, hepatomegaly, and accumulation of foamy macrophages in
      bone marrow and synovium, implying potential effectiveness of this approach in
      treatment of human MPS I.

PMID- 19384291
TI  - Chimeric receptors containing CD137 signal transduction domains mediate enhanced
      survival of T cells and increased antileukemic efficacy in vivo.
AB  - Persistence of T cells engineered with chimeric antigen receptors (CARs) has been
      a major barrier to use of these cells for molecularly targeted adoptive
      immunotherapy. To address this issue, we created a series of CARs that contain
      the T cell receptor-zeta (TCR-zeta) signal transduction domain with the CD28
      and/or CD137 (4-1BB) intracellular domains in tandem. After short-term expansion,
      primary human T cells were subjected to lentiviral gene transfer, resulting in
      large numbers of cells with >85% CAR expression. In an immunodeficient mouse
      xenograft model of primary human pre-B-cell acute lymphoblastic leukemia, human T
      cells expressing anti-CD19 CARs containing CD137 exhibited the greatest
      antileukemic efficacy and prolonged (>6 months) survival in vivo, and were
      significantly more effective than cells expressing CARs containing TCR-zeta alone
      or CD28-zeta signaling receptors. We uncovered a previously unrecognized, antigen
      independent effect of CARs expressing the CD137 cytoplasmic domain that likely
      contributes to the enhanced antileukemic efficacy and survival in tumor bearing
      mice. Furthermore, our studies revealed significant discrepancies between in
      vitro and in vivo surrogate measures of CAR efficacy. Together these results
      suggest that incorporation of the CD137 signaling domain in CARs should improve
      the persistence of CARs in the hematologic malignancies and hence maximize their
      antitumor activity.

PMID- 19384292
TI  - Mechanism of reduction in titers from lentivirus vectors carrying large inserts
      in the 3'LTR.
AB  - Self-inactivating (SIN) lentiviruses flanked by the 1.2-kb chicken hypersensitive
      site-4 (cHS4) insulator element provide consistent, improved expression of
      transgenes, but have significantly lower titers. The mechanism by which this
      occurs is unknown. Lengthening the lentiviral (LV) vector transgene cassette by
      an additional 1.2 kb by an internal cassette caused no further reduction in
      titers. However, when cHS4 sequences or inert DNA spacers of increasing size were
      placed in the 3'-long terminal repeat (LTR), infectious titers decreased
      proportional to the length of the insert. The stage of vector life cycle affected
      by vectors carrying the large cHS4 3'LTR insert was compared to a control vector:
      there was no increase in read-through transcription with insertion of the 1.2-kb
      cHS4 in the 3'LTR. Equal amount of full-length viral mRNA was produced in
      packaging cells and viral assembly/packaging was unaffected, resulting in
      comparable amounts of intact vector particles produced by either vectors.
      However, LV vectors carrying cHS4 in the 3'LTR were inefficiently processed
      following target-cell entry, with reduced reverse transcription and integration
      efficiency, and hence lower transduction titers. Therefore, vectors with large
      insertions in the 3'LTR are transcribed and packaged efficiently, but the LTR
      insert hinders viral-RNA (vRNA) processing and transduction of target cells.
      These studies have important implications in design of integrating vectors.

PMID- 19384293
TI  - Injection of bone marrow cell extract into infarcted hearts results in functional
      improvement comparable to intact cell therapy.
AB  - We compared therapeutic benefits of intramyocardial injection of unfractionated
      bone marrow cells (BMCs) versus BMC extract as treatments for myocardial
      infarction (MI), using closed-chest ultrasound-guided injection at a clinically
      relevant time post-MI. MI was induced in mice and the animals treated at day 3
      with either: (i) BMCs from green fluorescent protein (GFP)-expressing mice (n =
      14), (ii) BMC extract (n = 14), or (iii) saline control (n = 14). Six animals per
      group were used for histology at day 6 and the rest followed to day 28 for
      functional analysis. Ejection fraction was similarly improved in the BMC and
      extract groups versus control (40.6 +/- 3.4 and 39.1 +/- 2.9% versus 33.2 +/-
      5.0%, P < 0.05) with smaller scar sizes. At day 6 but not day 28, both therapies
      led to significantly higher capillary area and number of arterioles versus
      control. At day 6, BMCs increased the number of cycling cardiomyocytes (CMs)
      versus control whereas extract therapy resulted in significant reduction in the
      number of apoptotic CMs at the border zone (BZ) versus control. Intracellular
      components within BMCs can enhance vascularity, reduce infarct size, improve
      cardiac function, and influence CM apoptosis and cycling early after therapy
      following MI. Intact cells are not necessary and death of implanted cells may be
      a major component of the benefit.

PMID- 19384294
TI  - AAV2/8-mediated correction of OTC deficiency is robust in adult but not neonatal
      Spf(ash) mice.
AB  - Ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder,
      is associated with severe hyperammonemia accompanied by a high risk of
      neurological damage and death in patients presenting with the neonatal-onset
      form. Contemporary therapies, including liver transplantation, remain inadequate
      with considerable morbidity, justifying vigorous investigation of alternate
      therapies. Clinical evidence suggests that as little as 3% normal enzyme activity
      is sufficient to ameliorate the severe neonatal phenotype, making OTC deficiency
      an ideal model for the development of liver-targeted gene therapy. In this study,
      we investigated metabolic correction in neonatal and adult male OTC-deficient
      Spf(ash) mice following adeno-associated virus (AAV)2/8-mediated delivery of the
      murine OTC complementary DNA under the transcriptional control of a liver
      specific promoter. Substantially supraphysiological levels of OTC enzymatic
      activity were readily achieved in both adult and neonatal mice following a single
      intraperitoneal (i.p.) injection, with metabolic correction in adults being
      robust and life-long. In the neonates, however, full metabolic correction was
      transient, although modest levels of OTC expression persisted into adulthood.
      Although not directly testable in Spf(ash) mice, these levels were theoretically
      sufficient to prevent hyperammonemia in a null phenotype. This loss of expression
      in the neonatal liver is the consequence of hepatocellular proliferation and
      presents an added challenge to human therapy.

PMID- 19384295
TI  - Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers
      and may have application as a non-invasive biomarker of disease.
AB  - Large chromosomal regions can be suppressed in cancer cells as denoted by
      hypermethylation of neighbouring CpG islands and downregulation of most genes
      within the region. We have analysed the extent and prevalence of long-range
      epigenetic silencing at 2q14.2 (the first and best characterised example of
      coordinated epigenetic remodelling) and investigated its possible applicability
      as a non-invasive diagnostic marker of human colorectal cancer using different
      approaches and biological samples. Hypermethylation of at least one of the CpG
      islands analysed (EN1, SCTR, INHBB) occurred in most carcinomas (90%), with EN1
      methylated in 73 and 40% of carcinomas and adenomas, respectively. Gene
      suppression was a common phenomenon in all the tumours analysed and affected both
      methylated and unmethylated genes. Detection of methylated EN1 using bisulfite
      treatment and melting curve (MC) analysis from stool DNA in patients and controls
      resulted in a predictive capacity of, 44% sensitivity in positive patients (27%
      of overall sensitivity) and 97% specificity. We conclude that epigenetic
      suppression along 2q14.2 is common to most colorectal cancers and the presence of
      a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic
      disease.

PMID- 19384297
TI  - The impact of radiotherapy late effects on quality of life in gynaecological
      cancer patients.
AB  - The aims of this study were to assess changes in quality of life (QoL) scores in
      relation to radical radiotherapy for gynaecological cancer (before and after
      treatment up to 3 years), and to identify the effect that late treatment effects
      have on QoL. This was a prospective study involving 225 gynaecological cancer
      patients. A QoL instrument (European Organisation for the Research and Treatment
      of Cancer QLQ-C30) and late treatment effect questionnaire (Late Effects Normal
      Tissues - Subjective Objective Management Analysis) were completed before and
      after treatment (immediately after radiotherapy, 6 weeks, 12, 24 and 36 months
      after treatment). Most patients had acute physical symptoms and impaired
      functioning immediately after treatment. Levels of fatigue and diarrhoea only
      returned to those at pre-treatment assessment after 6 weeks. Patients with high
      treatment toxicity scores had lower global QoL scores. In conclusion, treatment
      with radiotherapy for gynaecological cancer has a negative effect on QoL, most
      apparent immediately after treatment. Certain late treatment effects have a
      negative effect on QoL for at least 2 years after radiotherapy. These treatment
      effects are centred on symptoms relating to the rectum and bowel, for example,
      diarrhoea, tenesmus and urgency. Future research will identify specific symptoms
      resulting from late treatment toxicity that have the greatest effect on QoL;
      therefore allowing effective management plans to be developed to reduce these
      symptoms and improve QoL in gynaecological cancer patients.

PMID- 19384296
TI  - Predictors of survival and toxicity in patients on adjuvant therapy with 5
      fluorouracil for colorectal cancer.
AB  - The present study aimed at investigating whether the simultaneous evaluation of
      pharmacokinetic, pharmacogenetic and demographic factors could improve prediction
      on toxicity and survival in colorectal cancer patients treated with adjuvant 5
      fluorouracil (5FU)/leucovorin therapy. One hundred and thirty consecutive, B2 and
      C Duke's stage colorectal cancer patients were prospectively enrolled. 5FU
      pharmacokinetics was evaluated at the first cycle. Thymidylate synthase (TYMS)
      5'UTR and 3'UTR polymorphisms and methylenetetrahydrofolate reductase (MTHFR)
      C677T and A1298C polymorphisms were assessed in peripheral leukocytes. Univariate
      and multivariate analyses were applied to evaluate which variables could predict
      chemotherapy-induced toxicity, disease-free survival (DFS) and overall survival
      (OS). Multivariate analysis showed that: (a) low 5FU clearance was an independent
      predictive factor for severe toxicity (OR=7.32; P<0.0001); (b) high-5FU clearance
      predicted poorer DFS (HR=1.96; P=0.041) and OS (HR=3.37; P=0.011); (c) advanced
      age was associated with shorter DFS (HR=3.34; P=0.0008) and OS (HR=2.66;
      P=0.024); (d) the C/C genotype of the MTHFR C677T polymorphism was protective
      against grade 3-4 toxicity (P=0.040); (e) none of the TYMS polymorphisms could
      explain 5FU toxicity or clinical outcome.

PMID- 19384298
TI  - Inhibition of tyrosine kinase receptors by SU6668 promotes abnormal stromal
      development at the periphery of carcinomas.
AB  - Dynamic contrast-enhanced (albumin-Gd-DTPA) magnetic resonance imaging, performed
      during 2 weeks of daily administration of an inhibitor of tyrosine kinase
      receptors (SU6668) in an HT-29 colon carcinoma model, revealed the onset of a
      hyper-enhancing rim, not observed in untreated tumours. To account for tissue
      heterogeneity in the quantitative analysis, we segmented tumours into three
      subunits automatically identified by cluster analysis of the enhancement curves
      using a k-means algorithm. Transendothelial permeability (Kps) and fractional
      plasma volume (fPV) were calculated in each subunit. An avascular and necrotic
      region, an intermediate zone and a well-vascularised periphery were reliably
      identified. During untreated tumour growth, the identified sub-regions did not
      substantially change their enhancement pattern. Treatment with SU6668 induced
      major changes at tumour periphery where a significant increase of Kps and fPV was
      observed with respect to control tumours. Histology revealed a sub-capsular layer
      composed of hyper-dense viable tumour cells in the periphery of untreated
      tumours. The rim of viable neoplastic cells was reduced in treated tumours, and
      replaced by loose connective tissue characterised by numerous vessels, which
      explains the observed hyper-enhancement. The present data show a peripheral
      abnormal development of cancer-associated stroma, indicative of an adaptive
      response to anti-angiogenic treatment.

PMID- 19384299
TI  - T-regulatory cell modulation: the future of cancer immunotherapy?
AB  - T-regulatory cells suppress anti-tumour immunity in cancer patients and in murine
      tumour models. Furthermore, their activity is likely to have an effect on the
      effectiveness of immunotherapeutic treatments for cancer. Here we describe the
      current status of developing clinical strategies for modulating Treg activity in
      cancer patients.

PMID- 19384306
TI  - Going through the phases. Response: Post-approval monitoring.

PMID- 19384300
TI  - High expression of tumour-associated trypsin inhibitor correlates with liver
      metastasis and poor prognosis in colorectal cancer.
AB  - Increased expression of tumour-associated trypsin inhibitor (TATI) in tumour
      tissue and/or serum has been associated with poor survival in various cancer
      forms. Moreover, a proinvasive function of TATI has been shown in colon cancer
      cell lines. In this study, we have examined the prognostic significance of tumour
      specific TATI expression in colorectal cancer, assessed by immunohistochemistry
      (IHC) on tissue microarrays (TMAs) with tumour specimens from two independent
      patient cohorts. Kaplan-Meier analysis and Cox proportional hazards modelling
      were used to estimate time to recurrence, disease-free survival and overall
      survival. In both cohorts, a high (>50% of tumour cells) TATI expression was an
      independent predictor of a significantly shorter overall survival. In cohort II,
      in multivariate analysis including age, gender, disease stage, differentiation
      grade, vascular invasion and carcinoembryonal antigen (CEA), high TATI expression
      was associated with a significantly decreased overall survival (HR=1.82; 95%
      CI=1.19-2.79) and disease-free survival (HR=1.56; 95% CI=1.05-2.32) in curatively
      treated patients. Moreover, there was an increased risk for liver metastasis in
      both cohorts that remained significant in multivariate analysis in cohort II
      (HR=2.85; 95% CI=1.43-5.66). In conclusion, high TATI expression is associated
      with liver metastasis and is an independent predictor of poor prognosis in
      patients with colorectal cancer.

PMID- 19384307
TI  - Going through the phases.

PMID- 19384308
TI  - Going through the phases. Response: Approve and monitor.

PMID- 19384309
TI  - Periurethral swelling in a female C3H/HeNCrMTV mouse.

PMID- 19384310
TI  - Diagnosis | Clitoral gland abscess.

PMID- 19384311
TI  - Routine canine ocular exam.
AB  - This column reviews the techniques used to carry out a basic ocular examination
      in a dog. With some modifications, the procedure can be used in most species.

PMID- 19384312
TI  - Analysis of environmental sound levels in modern rodent housing rooms.
AB  - Noise in animal housing facilities is an environmental variable that can affect
      hearing, behavior and physiology in mice. The authors measured sound levels in
      two rodent housing rooms (room 1 and room 2) during several 24-h periods. Room 1,
      which was subject to heavy personnel traffic, contained ventilated racks and
      static cages that housed large numbers of mice. Room 2 was accessed by only a few
      staff members, contained static cages only and housed fewer mice. In both rooms,
      background sound levels were usually about 80 dB, and transient noises caused
      sound levels to temporarily rise 30-40 dB above the baseline level; such peaks
      occurred frequently during work hours (8:30 AM to 4:30 PM) and infrequently
      during non-work hours. Noise peaks during work hours in room 1 occurred about two
      times as often as in room 2 (P = 0.01). Use of changing stations located in the
      rooms caused background noise to increase by about 10 dB. Loud noise and noise
      variability were attributed mainly to personnel activity. Attempts to reduce
      noise should concentrate on controlling sounds produced by in-room activities and
      experimenter traffic; this may reduce the variability of research outcomes and
      improve animal welfare.

PMID- 19384313
TI  - A serological survey to evaluate contemporary prevalence of viral agents and
      Mycoplasma pulmonis in laboratory mice and rats in western Europe.
AB  - To evaluate current prevalence rates of 24 viruses and of the bacterium
      Mycoplasma pulmonis, the authors retrospectively surveyed serological data
      obtained from laboratory mice and rats housed in more than 100 western European
      institutions. Serum samples were submitted to the authors' institution for
      testing between January 2007 and June 2008. The prevalence of an infection was
      defined as the percentage of tested samples that yielded positive results for a
      specific agent. In mice, the most commonly detected infectious agents were murine
      norovirus (prevalence of 31.8%), mouse hepatitis virus (5.5%), mouse rotavirus
      (1.7%) and parvoviruses (1.0%). In rats, parvoviruses (12.1%) and M. pulmonis
      (3.6%) were the most prevalent infectious agents. Most rodent parvovirus
      infections could be attributed to mouse parvovirus in mice and to rat minute
      virus or to Kilham rat virus in rats. These data suggest the importance of up-to
      date animal health monitoring programs and should stimulate the scientific
      community to further improve the microbiological quality of laboratory rodents.

PMID- 19384314
TI  - A critical appraisal of open- and closed-chest models of experimental myocardial
      ischemia.
AB  - Myocardial ischemia is one of the most extensively studied topics in modern
      cardiovascular research. Early investigators first reported experimental
      myocardial ischemia (EMI) in 1862. The open-chest (surgical) approach is a well
      developed model of EMI that enables researchers to directly access and observe
      the heart. With this approach, EMI is generally induced by surgical ligation of a
      coronary artery. A drawback of the open-chest model is the need for major
      surgery, which can result in local and systemic side effects. Alternative closed
      chest models of EMI have been developed; most of these models involve
      endovascular catheterization with coronary artery embolization or thrombosis.
      Closed-chest techniques eliminate the need for invasive surgery, and the
      resultant model is more physiologically similar to clinical myocardial ischemia
      than is EMI produced by artery ligation. The authors present a review of open-
      and closed-chest models of EMI and discuss the advantages and disadvantages of
      each approach.

PMID- 19384315
TI  - Continuing education.

PMID- 19384316
TI  - Update on Molecular Psychiatry: new publication guidelines and new ways to stay
      current.

PMID- 19384317
TI  - Modulation of hippocampal activation by genetic variation in the GRIK4 gene.

PMID- 19384318
TI  - The Ala54Thr polymorphism in the fatty acid-binding protein 2 gene leads to
      higher food intake in Japanese women.

PMID- 19384319
TI  - A GRIK4 variant conferring protection against bipolar disorder modulates
      hippocampal function.

PMID- 19384320
TI  - Is poverty a risk factor for CKD?

PMID- 19384321
TI  - Vasculitis syndromes: LAMP-2 illuminates pathogenesis of ANCA glomerulonephritis.
AB  - The discovery that antibodies to a bacterial antigen can cross-react with a
      mammalian protein to cause pauci-immune necrotizing and crescentic
      glomerulonephritis opens up new possibilities for the diagnosis and treatment of
      this condition.

PMID- 19384322
TI  - Pathology: donor biopsy evaluation at time of renal grafting.
AB  - How can we improve the diagnostic value of donor kidney graft biopsies and the
      management of renal transplant recipients? A recent study developed a morphologic
      scoring system -- the Maryland Aggregate Pathology Index -- to help predict long
      term renal graft survival from preimplantation donor organ biopsy findings.

PMID- 19384323
TI  - Dialysis: preventing hypophosphatemia during pediatric CRRT.
AB  - A recent report showed that hypophosphatemia is common in children undergoing
      continuous renal replacement therapy, and that adding phosphate to the
      replacement and dialysate solutions significantly reduced the incidence of this
      complication. Should such supplementation be routinely performed?

PMID- 19384324
TI  - Transplantation: sirolimus plus calcineurin inhibitors in transplantation.
AB  - A recent study reported that combination therapy with sirolimus plus either
      tacrolimus or ciclosporin resulted in effective immunosuppression in high-risk
      renal allograft recipients. Does such combination therapy really represent an
      advance in immunosuppressive therapy for these individuals?

PMID- 19384325
TI  - Vasculitis syndromes: which maintenance therapy for ANCA vasculitis?
AB  - Antineutrophil cytoplasmic antibody-associated vasculitides are usually treated
      with a combination of high-dose corticosteroids and cyclophosphamide therapy to
      induce remission, commonly followed by maintenance treatment with a less-toxic
      immunosuppressant. Azathioprine and methotrexate are both options for maintenance
      therapy, but whether one of these immunosuppressants is superior to the other is
      unclear.

PMID- 19384326
TI  - Acute kidney injury: intravenous fluid to prevent contrast-induced AKI.
AB  - Trials that compared sodium bicarbonate and sodium chloride for the prevention of
      contrast-induced acute kidney injury have yielded highly conflicting results. The
      authors of a recent meta-analysis endeavored to provide a definitive assessment
      of the relative efficacy of these two intravenous fluids.

PMID- 19384327
TI  - An update on acute postinfectious glomerulonephritis worldwide.
AB  - Postinfectious glomerulonephritis is an immunologic response of the kidney to
      infection, commonly triggered by streptococci, although many other organisms can
      cause the condition. In recent decades, the prevalence of postinfectious
      glomerulonephritis has tended to decline in most industrialized countries, but
      high rates persist in some developing communities. Nowadays, patients in
      developed countries are usually adult and male, and those with comorbidities such
      as diabetes and alcoholism are at increased risk of developing the disease. The
      acute presentation ranges from nephritic syndrome to asymptomatic
      glomerulonephritis. The exact pathophysiology of postinfectious
      glomerulonephritis is still unknown; however, several possible pathologic
      antigens are under investigation. The majority of children and patients with the
      epidemic form of postinfectious glomerulonephritis have an excellent prognosis,
      which contrasts with the poor long-term outcome of sporadic cases. Therapy is
      largely supportive unless renal function fails to recover after eradication of
      the causative organism. This Review focuses on acute postinfectious
      glomerulonephritis, and covers its epidemiology, presentation, pathology,
      pathogenesis, treatment and outcomes.

PMID- 19384328
TI  - Lithium nephrotoxicity revisited.
AB  - Lithium is widely used to treat bipolar disorder. Nephrogenic diabetes insipidus
      (NDI) is the most common adverse effect of lithium and occurs in up to 40% of
      patients. Renal lithium toxicity is characterized by increased water and sodium
      diuresis, which can result in mild dehydration, hyperchloremic metabolic acidosis
      and renal tubular acidosis. The concentrating defect and natriuretic effect
      develop within weeks of lithium initiation. After years of lithium exposure, full
      blown nephropathy can develop, which is characterized by decreased glomerular
      filtration rate and chronic kidney disease. Here, we review the clinical and
      experimental evidence that the principal cell of the collecting duct is the
      primary target for the nephrotoxic effects of lithium, and that these effects are
      characterized by dysregulation of aquaporin 2. This dysregulation is believed to
      occur as a result of the accumulation of cytotoxic concentrations of lithium,
      which enters via the epithelial sodium channel (ENaC) on the apical membrane and
      leads to the inhibition of signaling pathways that involve glycogen synthase
      kinase type 3beta. Experimental and clinical evidence demonstrates the efficacy
      of the ENaC inhibitor amiloride for the treatment of lithium-induced NDI;
      however, whether this agent can prevent the long-term adverse effects of lithium
      is not yet known.

PMID- 19384329
TI  - ANCA-associated vasculitis: from bench research to novel treatments.
AB  - Small-vessel vasculitic syndromes such as Wegener granulomatosis and microscopic
      polyangiitis, which are associated with circulating antineutrophil cytoplasmic
      autoantibodies, are an important cause of renal failure. Current
      immunosuppressive regimens based on cyclophosphamide have significantly improved
      survival in patients with these conditions. However, such treatments are toxic,
      increase the risk of infection and do not cure the disease; fresh approaches are,
      therefore, required. An increased understanding of the pathogenesis of these
      syndromes has allowed the rational use of newer therapies such as rituximab, an
      anti-CD20 chimeric monoclonal antibody that depletes B cells. Further
      understanding of the disease pathogenesis is crucial to the development of novel
      targeted therapies, which are urgently required to improve patient prognosis.
      Future potential therapies include molecules that block signaling pathways that
      are essential in the pathogenesis of these diseases.

PMID- 19384331
TI  - Lead poisoning from an Ayurvedic herbal medicine in a patient with chronic kidney
      disease.
AB  - BACKGROUND: A 60-year-old man with a history of diabetes and hypertension was
      referred to a nephrology clinic for investigation of his elevated serum
      creatinine level. INVESTIGATIONS: Physical examination; laboratory
      investigations, including measurement of whole-blood lead level, body lead burden
      and urine albumin:creatinine ratio; history of lead exposure and use of herbal
      medical products; and renal ultrasonography. DIAGNOSIS: Stage 3 chronic kidney
      disease that was probably worsened by consumption of lead in the form of an
      Ayurvedic herbal remedy. MANAGEMENT: Cessation of the herbal product, followed by
      lead-chelation therapy with calcium disodium ethylenediaminetetraacetic acid. The
      patient's whole-body lead burden and blood lead level decreased to acceptable
      levels and his serum creatinine value was within the normal range at final follow
      up.

PMID- 19384332
TI  - Water-diffusion slowdown in the human visual cortex on visual stimulation
      precedes vascular responses.
AB  - We used magnetic resonance imaging (MRI) to investigate the temporal dynamics of
      changes in water diffusion and blood oxygenation level-dependent (BOLD) responses
      in the brain cortex of eight subjects undergoing visual stimulation, and compared
      them with changes of the vascular hemoglobin content (oxygenated, deoxygenated,
      and total hemoglobin) acquired simultaneously from intrinsic optical recordings
      (near infrared spectroscopy). The group average rise time for the diffusion MRI
      signal was statistically significantly shorter than those of the BOLD signal and
      total hemoglobin content optical signal, which is assumed to be the fastest
      observable vascular signal. In addition, the group average decay time for the
      diffusion MRI also was shortest. The overall time courses of the BOLD and optical
      signals were strongly correlated, but the covariance was weaker with the
      diffusion MRI response. These results suggest that the observed decrease in water
      diffusion reflects early events that precede the vascular responses, which could
      originate from changes in the extravascular tissue.

PMID- 19384330
TI  - Cardiovascular risk and management in chronic kidney disease.
AB  - Chronic kidney disease (CKD) is associated with accelerated progression of
      cardiovascular disease, perhaps because patients with CKD have a high burden of
      traditional cardiovascular risk factors in addition to a range of nontraditional
      risk factors such as inflammation and abnormal metabolism of calcium and
      phosphate. Although the cardiovascular burden of CKD is well documented,
      potentially beneficial therapies are sometimes underused in patients with stage 3
      4 CKD and are rarely studied in patients on dialysis. In this Review, we describe
      the epidemiology of cardiovascular disease in patients with stage 3-5 CKD
      (excluding kidney transplant recipients) and outline cardiovascular risk factors
      that are relevant in this population; we then discuss the implications of this
      knowledge for the optimal management of cardiovascular risk in this setting.
      Finally, we highlight opportunities for further research.

PMID- 19384333
TI  - Post-ischemic helium provides neuroprotection in rats subjected to middle
      cerebral artery occlusion-induced ischemia by producing hypothermia.
AB  - During the past decade, studies on the manipulation of various inhaled inert
      gases during ischemia and/or reperfusion have led to the conclusion that inert
      gases may be promising agents for treating acute ischemic stroke and perinatal
      hypoxia-ischemia insults. Although there is a general consensus that among these
      gases xenon is a golden standard, the possible widespread clinical use of xenon
      experiences major obstacles, namely its availability and cost of production.
      Interestingly, recent findings have shown that helium, which is a cost-efficient
      inert gas with no anesthetic properties, can provide neuroprotection against
      acute ischemic stroke in vivo when administered during ischemia and early
      reperfusion. We have investigated whether helium provides neuroprotection in rats
      subjected to middle cerebral artery occlusion (MCAO) when administered after
      reperfusion, a condition prerequisite for the therapeutic viability and possible
      clinical use of helium. In this study, we show that helium at 75 vol% produces
      neuroprotection and improvement of neurologic outcome in rats subjected to
      transient MCAO by producing hypothermia on account of its high specific heat as
      compared with air.

PMID- 19384335
TI  - TAT-Hsp70-mediated neuroprotection and increased survival of neuronal precursor
      cells after focal cerebral ischemia in mice.
AB  - Cerebral ischemia stimulates endogenous neurogenesis within the subventricular
      zone and the hippocampal dentate gyrus of the adult rodent brain. However, such
      newly generated cells soon die after cerebral ischemia. To enhance postischemic
      survival of neural precursor cells (NPC) and long-lasting neural regeneration, we
      applied the antiapoptotic chaperone heat shock protein 70 (Hsp70) fused to a cell
      penetrating peptide derived from the HIV TAT to ensure delivery across the blood
      brain barrier and the cell membrane. After transient focal cerebral ischemia in
      mice, TAT-Hsp70 was intravenously injected concomitant with reperfusion and
      additionally on day 14 after stroke. TAT-Hsp70 treatment resulted in smaller
      infarct size (27.1+/-9.0 versus 109.0+/-14.0 and 88.5+/-26.0 mm(3) in controls)
      and in functional improvement as assessed by the rota rod, tight rope, and water
      maze tests when compared with saline- and TAT-hemagglutinin-treated controls. In
      addition, postischemic survival of endogenous doublecortin (Dcx)-positive NPC was
      improved within the lesioned striatum of TAT-Hsp70-treated animals for up to 4
      weeks after stroke without changing overall cell proliferation of BrdU(+) cells.
      Thus, TAT-Hsp70 treatment after stroke may be a promising tool to act
      neuroprotective and improve postischemic functional outcome, and also to increase
      survival of endogenous NPC after stroke.

PMID- 19384334
TI  - A new model of cortical stroke in the rhesus macaque.
AB  - Primate models are essential tools for translational research in stroke but are
      reportedly inconsistent in their ability to produce cortical infarcts of
      reproducible size. Here, we report a new stroke model using a transorbital,
      reversible, two-vessel occlusion approach in male rhesus macaques that produces
      consistent and reproducible cortical infarcts. The right middle cerebral artery
      (distal to the orbitofrontal branch) and both anterior cerebral arteries were
      occluded with vascular clips. Bilateral occlusion of the anterior cerebral artery
      was critical for reducing collateral flow to the ipsilateral cortex. Reversible
      ischemia was induced for 45, 60, or 90 mins (n=2/timepoint) and infarct volume
      and neurologic outcome were evaluated. The infarcts were located predominantly in
      the cortex and increased in size with extended duration of ischemia determined by
      T(2)-weighted magnetic resonance imaging . Infarct volume measured by 2,3,5
      triphenyl tetrazolium chloride and cresyl violet staining corroborated magnetic
      resonance imaging results. Neurologic deficit scores worsened gradually with
      longer occlusion times. A subset of animals (n=5) underwent 60 mins of ischemia
      resulting in consistent infarct volumes primarily located to the cortex that
      correlated well with neurologic deficit scores. This approach offers promise for
      evaluating therapeutic interventions in stroke.

PMID- 19384336
TI  - Bone marrow stromal cells increase oligodendrogenesis after stroke.
AB  - Oligodendrocytes are sensitive to ischemic damage. The Sonic hedgehog (Shh)
      pathway is critical in oligodendrogenesis; Gli1 is the principal effector of Shh
      signaling. We investigated oligodendrogenesis and Shh/Gli1 pathway activation
      after bone marrow stromal cell (BMSC) treatment of stroke in rats. Rats were
      subjected to the middle cerebral artery occlusion (MCAo). BMSCs have been shown
      to promote functional recovery post stroke. A therapeutic dose of BMSC (3 x 10(6)
      cells) treatment was initiated 1 day after MCAo. Immunohistochemistry was carried
      out to measure the oligodendrocyte progenitor cells, oligodendrocytes, myelin,
      and expressions of Shh and Gli1 at 14 days after MCAo. Gene expression of Shh and
      Gli1 was tested at 2 days after MCAo. An in vitro study was used to investigate
      the effects of BMSC on a premature oligodendrocyte cell line (N20.1 cells). BMSC
      treatment significantly increased O4(+) oligodendrocytes, MBP(+) area, and
      bromodeoxyuridine (BrdU)(+), NG2(+), BrdU(+)-NG2(+) cells, and mRNA and protein
      expressions of Shh and Gli1 in the ipsilateral brain of the MCAo rats than that
      in phosphate buffered saline (PBS)-treated rats. BMSCs promoted N20.1 cell
      proliferation and Gli1 mRNA expression, and these effects were abolished by the
      Shh pathway inhibitor cyclopamine. These data indicate that the BMSC treatment
      stimulates oligodendrogenesis by activation of the Shh/Gli1 pathway post stroke.

PMID- 19384337
TI  - Joint analysis of spatial genetic structure and inbreeding in a managed
      population of Scots pine.
AB  - We have investigated the fine-scale spatial genetic structure in a managed Scots
      pine forest. For this purpose, we perform a Bayesian genetic-cluster analysis of
      96 geographically mapped individual seed trees of Swedish Scots pine based on 14
      microsatellite loci. The analysis was carried out with the recently developed
      program GENECLUST (Francois et al., 2006), which provides the facility to jointly
      incorporate both spatial information from a geographical neighborhood structure
      through a Potts-Dirichlet model and account for variable degrees of inbreeding
      within the clusters. To evaluate whether inbreeding and spatial interaction
      should be included in the best-fitting statistical model for our data, we used
      the deviance information criterion (DIC), a weighted measure of model fit that
      accounts for an effective number of free parameters in a model. Analysis shows
      that a model with a single estimated cluster, with high levels of inbreeding
      (0.25) and with a moderate amount of spatial dependency within the unique cluster
      (Psi=0.2-0.4), best explains the data. We also carried out Bayesian parentage
      analysis, which enabled us to exclude the possibility that the sample constitutes
      one single full-sib family.

PMID- 19384338
TI  - Evolutionary conserved lineage of Angela-family retrotransposons as a genome-wide
      microsatellite repeat dispersal agent.
AB  - A detailed examination of 45 pea (Pisum sativum L.) simple sequence repeat (SSR)
      loci revealed that 21 of them included homologous sequences corresponding to the
      long terminal repeat (LTR) of a novel retrotransposon. Further investigation,
      including full-length sequencing, led to its classification as an RLC-Angela
      family-FJ434420 element. The LTR contained a variable region ranging from a
      simple TC repeat (TC)(11) to more complex repeats of TC/CA, (TC)(12-30), (CA)(18
      22) and was up to 146 bp in length. These elements are the most abundant
      Ty1/copia retrotransposons identified in the pea genome and also occur in other
      legume species. It is interesting that analysis of 63 LTR-derived sequences
      originating from 30 legume species showed high phylogenetic conservation in their
      sequence, including the position of the variable SSR region. This extraordinary
      conservancy led us to the proposition of a new lineage, named MARTIANS, within
      the Angela family. Similar LTR structures and partial sequence similarities were
      detected in more distant members of this Angela family, the barley BARE-1 and
      rice RIRE-1 elements. Comparison of the LTR sequences from pea and Medicago
      truncatula elements indicated that microsatellites arise through the expansion of
      a pre-existing repeat motif. Thus, the presence of an SSR region within the LTR
      seems to be a typical feature of this MARTIANS lineage, and the evidence gathered
      from a wide range of species suggests that these elements may facilitate
      amplification and genome-wide dispersal of associated SSR sequences. The
      implications of this finding regarding the evolution of SSRs within the genome,
      as well as their utilization as molecular markers, are discussed.

PMID- 19384339
TI  - Mitochondrial phylogeography of the European ground squirrel, Spermophilus
      citellus, yields evidence on refugia for steppic taxa in the southern Balkans.
AB  - The spatial genetic structure of the European ground squirrel, a species
      characteristic of the short-grass steppe, was investigated on the basis of a 1140
      bp cyt b gene sequence. The phylogeographical architecture of this species is
      expected to shed light on the putative long-term presence of the steppic
      ecosystem in south-eastern Europe and the evolutionary consequences of glacial
      cycles as forcing factors in speciation. Among 31 haplotypes, three highly
      divergent phylogenetic lineages (Southern, Northern and Jakupica) were
      recognized. This result suggests the past existence of an allopatric
      fragmentation event caused by effective biogeographical barriers. The Southern
      lineage consisted of the southernmost populations, those from Greece, Macedonia
      and European Turkey, and showed the highest divergence from all other samples.
      Haplotypes of the Northern lineage showed little geographical structure, with
      dispersal on both sides of the Danube River and in both of the two main
      geographical fragments of the species. The Jakupica lineage is a geographical
      isolate on a high plateau in central Macedonia. The estimated time for divergence
      of the Southern lineage (ca. 0.58 Mya) suggests the long-term persistence of a
      short-grass steppic refugium in the southern Balkans. Although the divergence
      between the Northern and Jakupica lineages occurred more recently (ca. 0.3 Mya),
      it still putatively predates two glacial cycles. The three phylogeographical
      lineages of the European ground squirrel should be regarded as independent units
      for conservation management purposes.

PMID- 19384340
TI  - Spruce colonization at treeline: where do those seeds come from?
AB  - At treeline, selection by harsh environmental conditions sets an upward limit to
      arboreal vegetation. Increasing temperatures and the decline of traditional
      animal raising have favoured an upward shift of treeline in the last decades.
      These circumstances create a unique opportunity to study the balance of the main
      forces (selection and gene flow) that drive tree migration. We conducted a
      parentage analysis sampling and genotyping with five microsatellite markers in
      all Norway spruce individuals (342 juveniles and 23 adults) found in a recently
      colonized treeline area (Paneveggio forest, Eastern Alps, Italy). Our goal was to
      evaluate local reproductive success versus gene flow from the outside. We were
      able to identify both parents among local adults for only 11.1% of the juveniles.
      In the gamete pool we sampled, two-thirds were not produced locally. Effective
      seed dispersal distance distribution was characterized by a peak far from the
      seed source (mean 344.66 m+/-191.02 s.d.). Reproductive success was skewed, with
      six local adults that generated almost two-thirds (62.4%) of juveniles with local
      parents. Our findings indicate that, although a few local adults seem to play an
      important role in the colonization process at treeline, large levels of gene flow
      from outside were maintained, suggesting that the potential advantages of local
      adults (such as local adaptation, proximity to the colonization area,
      phenological synchrony) did not prevent a large gamete immigration.

PMID- 19384341
TI  - Evolutionary implications of discordant clines across the Baltic Mytilus hybrid
      zone (Mytilus edulis and Mytilus trossulus).
AB  - It is well established that reproductive isolation often arises from genome
      incompatibilities and that genes encoding reproductive traits are less prone to
      introgression. Hybrid zones of Mytilus trossulus and Mytilus edulis provide an
      intriguing model to assess reproductive isolation. Although gene flow is
      restricted in North America, introgression is pervasive in the Baltic. This study
      aimed at analyzing the shape of multilocus clines across the Baltic contact zone
      between M. edulis and M. trossulus to infer mechanisms of restriction to gene
      flow. We use maximum likelihood methods to construct the best fitting individual
      clines for five markers located on biparentally inherited autosomes and
      paternally and maternally inherited mitochondrial DNA (mtDNA). Strong cline shape
      differences among markers suggest that reproductive isolation arising from genome
      wide incompatibilities is weak, and that these discrepancies possibly result from
      genetic drift, hybrid zone movement or marker-specific selection. However, the
      finding of a common cline center for M7 lysin (involved in fertilization) and
      paternally transmitted mtDNA (causing nuclear-mitochondrial incompatibilities in
      hybrids) suggest that these loci may play a role in incomplete reproductive
      isolation.

PMID- 19384342
TI  - The genetic code has a 'shift' key.

PMID- 19384343
TI  - Geographically localised bursts of ribosomal DNA mobility in the grasshopper
      Podisma pedestris.
AB  - We report extraordinary variation in the number and the chromosomal location of
      ribosomal DNA (rDNA) arrays within populations of the alpine grasshopper Podisma
      pedestris; even greater differences were found between populations. The sites
      were detected by in situ hybridisation of labelled rDNA to chromosomal
      preparations. The total number of rDNA sites in an individual varied from three
      to thirteen. In the most extreme case, individuals from populations only 10 km
      apart had no rDNA loci in common. A survey of the geographical distribution of
      this variation identified clusters of populations with relatively similar
      chromosomal distribution of rDNA loci. These clusters correspond to those
      identified earlier by analysis of rDNA sequences. To explain this geographical
      clustering, we reconstructed the post-glacial colonisation of the region by
      assuming that the species' distribution has ascended to its current altitudinal
      range as the climate warmed. The reconstruction suggests that each cluster is
      descended from a colonisation route up a different alpine valley. That history
      would imply rapid establishment of rDNA differences, conceivably during the last
      10,000 years since the last glaciation. The proposal for rapid change is
      consistent with the extensive within-population variation, which indicates that
      the processes responsible for the change in rDNA's chromosomal location continue
      to occur at a higher rate. We discuss whether our reconstruction of colonisation
      routes implies movement of the hybrid zone, which would indicate that a neo-XY
      sex chromosome system has spread through extant populations.

PMID- 19384344
TI  - Optimal mobilization method and CD34+ dose calculation for autologous PBSC
      transplant in myeloma patients: two important unresolved questions.

PMID- 19384345
TI  - Functional identification of the promoter of SLC4A5, a gene associated with
      cardiovascular and metabolic phenotypes in the HERITAGE Family Study.
AB  - The sodium bicarbonate cotransporter gene SLC4A5, associated earlier with
      cardiovascular phenotypes, was tested for associations in the HERITAGE Family
      Study, and possible mechanisms were investigated. Twelve tag-single nucleotide
      polymorphisms (SNPs) covering the SLC4A5 gene were analyzed in 276 Black and 503
      White healthy, sedentary subjects. Associations were tested using a variance
      components-based (QTDT) method with data adjusted for age, sex and body size. In
      Whites, rs6731545 and rs7571842 were significantly associated with resting and
      submaximal exercise pulse pressure (PP) (0.0004 <P<0.0007 and 0.002<P<0.003
      respectively). Additionally, rs6731545 was associated with submaximal-exercise
      systolic blood pressure (SBP) and rate pressure product (P=0.002, both). New
      associations between rs6731545 and submaximal-exercise VO(2) (P=0.003), rs7587117
      and rs7571842 and VCO(2) (0.0005<P<0.0009) and rs828853 and VE (P=0.002) were
      found. All these associations had a FDR<0.05. Single-marker associations were
      confirmed in haplotype analyses. Using in silico analysis, evidence was found for
      a main and an alternative promoter for SLC4A5. Specific promoter activity was
      experimentally confirmed using reporter constructs targeting both promoters in
      three physiologically relevant cell lines. Re-sequencing of 32 individuals having
      opposite homozygotes for rs7571842 and rs6731545 and exhibiting significantly
      different phenotypes showed no SNPs in the alternative promoter and no
      differences between the groups with SNPs in the main promoter. Also, of all known
      SLC4A5-coding SNPs, only one synonymous SNP was detected. Summarizing, the
      observed associations with resting and submaximal-exercise cardiovascular and
      metabolic traits in the HERITAGE Family Study are likely due to neither variation
      in the promoter nor known coding SNPs of SLC4A5.

PMID- 19384346
TI  - Copy number variation and association analysis of SHANK3 as a candidate gene for
      autism in the IMGSAC collection.
AB  - SHANK3 is located on chromosome 22q13.3 and encodes a scaffold protein that is
      found in excitatory synapses opposite the pre-synaptic active zone. SHANK3 is a
      binding partner of neuroligins, some of whose genes contain mutations in a small
      subset of individuals with autism. In individuals with autism spectrum disorders
      (ASDs), several studies have found SHANK3 to be disrupted by deletions ranging
      from hundreds of kilobases to megabases, suggesting that 1% of individuals with
      ASDs may have these chromosomal aberrations. To further analyse the involvement
      of SHANK3 in ASD, we screened the International Molecular Genetic Study of Autism
      Consortium (IMGSAC) multiplex family sample, 330 families, for SNP association
      and copy number variants (CNVs) in SHANK3. A collection of 76 IMGSAC Italian
      probands from singleton families was also examined by multiplex ligation
      dependent probe amplification for CNVs. No CNVs or SNP associations were found
      within the sample set, although sequencing of the gene was not performed. Our
      data suggest that SHANK3 deletions may be limited to lower functioning
      individuals with autism.

PMID- 19384347
TI  - A new function for an old organelle: microtubule nucleation at the Golgi
      apparatus.

PMID- 19384348
TI  - Gene body DNA methylation in plants: a means to an end or an end to a means?

PMID- 19384349
TI  - A lipid kinase controls the maintenance of dendritic spines.

PMID- 19384353
TI  - Partial destruction of sensitivity in non-ideal interferometric detection of
      gravitational waves.
AB  - We have studied the interferometric sensitivity for gravitational wave detection
      explicitly including the photodetector efficiency. We show that the sensitivity
      is very strongly affected by non-ideal photodetector efficiency when we inject a
      squeezed signal, as compared to the ordinary vacuum case. Quantum limits and
      resonance are also discussed for short time detections.

PMID- 19384352
TI  - Introduction.
AB  - Quantum noise reduction in optical systems and the determination of quasi
      distribution functions, in particular Wigner functions, to describe quantum
      optical states, have been central issues in quantum optics for a number of years.
      The generation of sources of squeezed light has opened very exciting
      possibilities of ultrahigh precision measurements beyond the standard quantum
      limit, by either interferometric or spectroscopic means. In the present issue,
      the paper by Mundarain and Orszag discusses the interferometric detection of
      ultrasmall signals, in particular gravitational waves, when one injects a
      squeezed state in the unused port of the interferometer. The authors find that
      the sensitivity of the system is very strongly affected by the quantum efficiency
      of the non-ideal photodetectors, when the squeezed signal is injected, as opposed
      to the ordinary vacuum case where the effects are rather small. This imposes
      strong conditions on the quality of those photodetectors. The standard quantum
      limit and the corresponding minimum detectable gravitational amplitude is also
      discussed in general, for short time measurements.

PMID- 19384354
TI  - Sampling quantum phase space with squeezed states.
AB  - We study the application of squeezed states in a quantum optical scheme for
      direct sampling of the phase space by photon counting. We prove that the
      detection setup with a squeezed coherent probe field is equivalent to the probing
      of the squeezed signal field with a coherent state. An example of the Schr
      odinger cat state measurement shows that the use of squeezed states allows one to
      detect clearly the interference between distinct phase space components despite
      losses through the unused output port of the setup.

PMID- 19384355
TI  - Non-classical states of the electromagnetic field in cavity QED.
AB  - We propose simple experiments in cavity quantum electrodynamics leading, for the
      first time, to the measurement of negative values of the Wigner function of an
      electromagnetic field. We also show that the realization of a controlled-not gate
      within the framework of cavity QED is a special case of our proposal, and is
      equivalent to the measurement of the Wigner function of a one-photon field at the
      origin of phase space.

PMID- 19384356
TI  - Optical homodyne tomography of information carrying laser beams.
AB  - Optical homodyne tomography (OHT) is a tool that allows the reconstruction of
      Wigner functions for each detection frequency of a propagating optical beam. It
      can measure probability distribution functions (PDF's) of the field amplitude for
      any given quadrature of interest. We demonstrate OHT for a range of classical
      optical states with constant and time varying modulations and show the advantage
      of OHT over conventional homodyne detection. The OHT simultaneously determines
      the signal to noise ratio in both amplitude and phase quadratures. We show that
      highly non-Gaussian Wigner functions can be obtained from incoherent
      superpositions of optical states.

PMID- 19384357
TI  - Free-electron laser exploiting a superlattice-like medium.
AB  - Amplification in free-electron lasers exploiting media with periodically
      modulated refractive indices is studied in the regime of a large modulation. The
      conditions for realization of the large-modulation regime in a superlattice-like
      medium are established. The maximized gain, the corresponding saturation field
      and efficiency, as well as the optimal electron energy and propagation direction
      are determined. It is shown that the large-modulation regime makes it possible to
      extend significantly the operation frequency domain of the FEL employing a low
      relativistic electron beam. Relationship with the Cherenkov and stimulated
      resonance-transition-radiation FELs is discussed. This research is partially
      supported by RFBR grant 97-02-17783.

PMID- 19384358
TI  - Vacuum-induced jitter in spatial solitons.
AB  - We perform a calculation to determine how quantum mechanical fluctuations
      influence the propagation of a spatial soliton through a nonlinear material. To
      do so, we derive equations of motion for the linearized operators describing the
      deviation of the soliton position and transverse momentum from those of a
      corresponding classical solution to the nonlinear wave equation, and from these
      equations we determine the quantum uncertainty in the soliton position and
      transverse momentum. We find that under realistic laboratory conditions the
      quantum uncertainty in position is several orders of magnitude smaller the
      classical width of the soliton. This result suggests that the reliability of
      photonic devices based on spatial solitons is not compromised by quantum
      fluctuations.

PMID- 19384359
TI  - Doughnut-like laser beam output formation by intracavity flexible controlled
      mirror.
AB  - The formation of the given low loss and large beamwidth doughnut-like fundamental
      mode of stable resonator by an intracavity flexible mirror is discussed. The
      mirror is a bimorph one with one round and two ring controlling electrodes. An
      inverse propagation method is used to determine the appropriate shape of the
      controlled mirror. The mirror reproduces the shape with minimal RMS error by
      combining weights of experimentally measured response functions of the mirror
      sample. The voltages applied to each mirror electrode are calculated. The
      calculations are carried out for industrial CW CO2 laser.

PMID- 19384360
TI  - A fast, robust pattern recognition asystem for low light level image registration
      and its application to retinal imaging.
AB  - We describe an image processing system which we have developed to align
      autofluorescence and high-magnification images taken with a laser scanning
      ophthalmoscope. The low signal to noise ratio of these images makes pattern
      recognition a non-trivial task. However, once n images are aligned and averaged,
      the noise levels drop by a factor of n and the image quality is improved. We
      include examples of autofluorescence images and images of the cone photoreceptor
      mosaic obtained using this system.

PMID- 19384361
TI  - Introduction.
AB  - The pace of technological advancement of Optical Coherence Tomography (OCT) over
      the last several years has been extremely rapid. The field has progressed from
      one-dimensional low-coherence ranging to full three-dimensional imaging with
      individual two-dimensional images aquired at near video rate in a span of less
      than eight years. Imaging applications have included polymers and advanced
      composites, Ophthalmology, Developmental Biology, Gastroenterology, Urology,
      Cardiology, Neurology, and Gynecology. These preliminary studies indicate the
      great potential for OCT to make a significant impact, especially in clinical
      medicine.

PMID- 19384362
TI  - OCT elastography: imaging microscopic deformation and strain of tissue.
AB  - Optical coherence tomography (OCT) has been applied to the study of the
      microscopic deformation of biological tissue under compressive stress. We
      describe the hardware and theory of operation of an OCT elastography system that
      measures internal displacements as small as a few micrometers by using 2D cross
      correlation speckle tracking. Results obtained from gelatin scattering models,
      pork meat, and intact skin suggest possible medical applications of the
      technique.

PMID- 19384363
TI  - Imaging thermally damaged tissue by Polarization Sensitive Optical Coherence
      Tomography.
AB  - Polarization Sensitive Optical Coherence Tomography (PS- OCT) was used to image
      the reduction of birefringence in biological tissue due to thermal damage.
      Through simultaneous detection of the amplitude of signal fringes in orthogonal
      polarization states formed by interference of light backscattered from turbid
      media and a mirror in the reference arm of a Michelson interferometer, changes in
      the polarization due to the optical phase delay between light propagating along
      the fast and slow axes of birefringent media were measured. Inasmuch as fibrous
      structures in many biological tissues in uence the polarization state of light
      backscattered, PS-OCT is a potentially useful technique to image the structural
      properties of turbid biological materials. Birefringence of collagen, a
      constituent of many biological tissues, is reduced by denaturation that takes
      place at a temperature between 56-65 0 C, thus providing an "optical marker" for
      thermal damage. Images showing reduction of birefringence due to thermal damage
      in porcine tendon and skin are presented and demonstrate the potential of PS-OCT
      for burn depth assessment.

PMID- 19384364
TI  - In vivo video rate optical coherence tomography.
AB  - An optical coherence tomography system is described which can image up to video
      rate. The system utilizes a high power broadband source and real time image
      acquisition hardware and features a high speed scanning delay line in the
      reference arm based on Fourier-transform pulse shaping technology. The theory of
      low coherence interferometry with a dispersive delay line, and the operation of
      the delay line are detailed and the design equations of the system are presented.
      Real time imaging is demonstrated in vivo in tissues relevant to early human
      disease diagnosis (skin, eye) and in an important model in developmental biology
      (Xenopus laevis).

PMID- 19384365
TI  - Dental OCT.
AB  - We present here the first in vivo optical coherence tomography (OCT) images of
      human dental tissue. A novel dental optical coherence tomography system has been
      developed. This system incorporates the interferometer sample arm and transverse
      scanning optics into a handpiece that can be used intraorally to image human
      dental tissues. The average imaging depth of this system varied from 3 mm in hard
      tissues to 1.5 mm in soft tissues. We discuss the application of this imaging
      system for dentistry and illustrate the potential of our dental OCT system for
      diagnosis of periodontal disease, detection of caries, and evaluation of dental
      restorations.

PMID- 19384366
TI  - In vivo OCT imaging of hard and soft tissue of the oral cavity.
AB  - We use optical coherence tomography (OCT) to perform a comprehensive program of
      in vivo and in vitro structural imaging of hard and soft tissues within the oral
      cavity. We have imaged the different types of healthy oral mucosa as well as
      normal and abnormal tooth structure. OCT is able to differentiate between the
      various types of keratinized and non-keratinized mucosa with high resolution. OCT
      is also able to provide detailed structural information on clinical abnormalities
      (caries and non-caries lesions) in teeth and provide guidance in dental
      restorative procedures. Our investigations demonstrate the utility of OCT as a
      diagnostic imaging modality in clinical and research dentistry.

PMID- 19384367
TI  - Investigating pulsed dye laser-blood vessel interaction with color Doppler
      optical coherence tomography.
AB  - A non-invasive method of imaging laser irradiated blood vessels has been achieved
      using Color Doppler Optical Coherence Tomography (CDOCT). This method may
      increase understanding of the mechanisms behind treatment of vascular disorders.
      The CDOCT system used a 1280 nm center wavelength superluminescent diode. A 585
      nm, 360 aes pulsed dye laser was used to irradiate hamster dorsal skin flap
      window preparations. Irradiation sites were imaged with CDOCT prior to,
      immediately after, and 24 hours after laser irradiation. The processed CDOCT
      signal provided an estimate of the blood flow velocity. An increase in the blood
      vessel backscattered signal was observed as blood or vessel walls were
      coagulated. A decrease in damaged blood vessel reflectivity occurred after twenty
      four hours.

PMID- 19384368
TI  - Endoscopic applications of optical coherence tomography.
AB  - We report results of application of our endoscopic optical coherence tomography
      (EOCT) system in clinical experiments to image human internal organs. Based on
      the experience of studying more than 100 patients, we make first general
      conclusions on the place and capabilities of this method in diagnosing human
      mucous membranes. It is demonstrated that EOCT can serve for several clinical
      purposes such as performing directed biopsy, monitoring functional states of
      human body, guiding surgical and other treatments and monitoring post-operative
      recovery processes. We show that applications of OCT are more informative in the
      case of internal organs covered by epithelium separated from underlying stroma by
      a smooth basal membrane and therefore concentrate on the results of the EOCT
      study of three internal organs, namely of larynx, bladder, and uterine cervix.
      Finally, we report first examination of internal organs in abdomen with the use
      of laparoscopic OCT.

PMID- 19384369
TI  - Stabilization and Structure of wave packets in Rydberg atoms ionized by a strong
      light field.
AB  - New features of the phenomenon of interference stabilization of Rydberg atoms are
      found to exist. The main of them are: (i) dynamical stabilization, which means
      that in case of pulses with a smooth envelope the time-dependent residual
      probability for an atom to survive in bound states remains almost constant in the
      middle part of a pulse (at the strongest fields); (ii) existence of the strong
      field stabilization of the after-pulse residual probability in case of pulses
      longer than the classical Kepler period; and (iii) pulsation of the time
      dependent Rydberg wave packet formed in the process of photoionization.

PMID- 19384370
TI  - Energy flow in light-coupling masks for lensless optical lithography.
AB  - We illustrate the propagation of light in a new type of coupling mask for
      lensless optical lithography. Our investigation shows how the different elements
      comprising such masks contribute to the definition of an optical path that allows
      the exposure of features in the 100-nm-size range in the photoresist.

PMID- 19384371
TI  - Effect of molecular concentrations in tissu-simulating phantoms on images
      obtained using diffuse reflectance polarimetry.
AB  - We have investigated the possibility of using diffuse reflectance polarimetry to
      detect changes caused by different molecular compounds and concentrations in
      tissue-simulating phantoms. The effects of glucose, B-alanine and l-lysine at
      different concentrations in turbid media have been investigated separately. This
      approach is based on the effect of optical properties on the polarization state
      of light. The results show that this method has potential for determining changes
      in molecular concentrations in highly scattering biological media from
      polarization images.

PMID- 19384372
TI  - Pump-probe switching in gain-switched lasers.
AB  - We report a novel pump-probe switching phenomenon exhib-ited by gain-switched
      vibronic lasers under dual pulse excitation. A spatio-temporal rate equation
      model reveals the mechanismresponsible, and predicts observations of pump-probe
      switching in a Cr:forsterite laser under pulsed 1064nm excitation. The
      sensitivity of this energy storage-extraction process to the pump and probe
      fluences and their temporal separation is investigated for switching in the
      nanosecond and microsecond excitation regimes.

PMID- 19384373
TI  - Characteristics of a Yb-doped superfluorescent fiber source for use in optical
      coherence tomography.
AB  - We have used a newly developed Yb-doped high-power fiber source in an optical
      coherence tomography (OCT) apparatus. We have analyzed various properties of
      interest for OCT measurements such as spectral shape, related gate width, central
      wavelength, bandwidth, and power output.

PMID- 19384374
TI  - Introduction.
AB  - This special issue of Optics Express focuses on a number of exciting new
      applications in biology and medicine utilizing nonlinear microscopy and reflected
      light confocal optical microscopy.

PMID- 19384375
TI  - Prospects of nonlinear microscopy in the next decade: an overview.
AB  - A brief overview of nonlinear microscopy in biomedicine is presented. Some of the
      main results of the contributions of the Focus Issue are also briefly discussed.

PMID- 19384376
TI  - Third harmonic generation microscopy.
AB  - Third harmonic generation microscopy is used to make dynamical images of living
      systems for the first time. A 100 fs excitation pulse at 1.2 aem results in a 400
      nm signal which is generated directly within the specimen. Chara plant rhizoids
      have been imaged, showing dynamic plant activity, and non-fading image
      characteristics even with continuous viewing, indicating prolonged viability
      under these THG-imaging conditions.

PMID- 19384377
TI  - Multiphoton laser scanning microscopy for four-dimensional analysis of
      Caenorhabditis elegans embryonic development.
AB  - Multiphoton laser scanning microscopy (MPLSM) enables the production of long
      timelapse recordings from live fluorescent specimens. 1047- and 900-nm excitation
      were used to image both a vital fluorescent membrane probe, FM 4-64, and a
      modified green fluorescent protein (GFP) in live Caenorhabditis elegans embryos.
      Automated four-dimensional (4D) data collection yielded individual recordings
      comprising thousands of images, each allowing analysis of all of the cell
      divisions, contacts, migrations, and fusions that occur during a span of several
      hours of embryogenesis.

PMID- 19384378
TI  - Three-dimensional microscopic tomographic imagings of the cataract in a human
      lens in vivo.
AB  - The problem of three-dimensional visualization of a human lens in vivo has been
      solved by a technique of volume rendering a transformed series of 60 rotated
      Scheimpflug (a dual slit reflected light microscope) digital images. The data set
      was obtained by rotating the Scheimpflug camera about the optic axis of the lens
      in 3 degree increments. The transformed set of optical sections were first
      aligned to correct for small eye movements, and then rendered into a volume
      reconstruction with volume rendering computer graphics techniques. To help
      visualize the distribution of lens opacities (cataracts) in the living, human
      lens the intensity of light scattering was pseudocolor coded and the cataract
      opacities were displayed as a movie.

PMID- 19384379
TI  - Two-Photon deep tissue ex vivo imaging of mouse dermal and subcutaneous
      structures.
AB  - The non-invasive determination of deep tissue three dimensional structure and
      biochemistry is the ultimate goal of optical biopsy. Two-photon microscopy has
      been shown to be a particularly promising approach. The use of infrared radiation
      in two-photon microscopy is critical for deep tissue imaging since tissue
      absorption and scattering coefficients for infrared light are much lower than for
      shorter wavelengths. Equally important, tissue photodamage is localized to the
      focal region where fluorescence excitation occurs. This report demonstrates that,
      by means of high resolution two-photon microscopy, skin and subcutaneous tissue
      structures can be imaged utilizing their endogenous fluorescence. From a freshly
      prepared tissue punch of a mouse ear, we were able to 3D resolve both the living
      and cornified keratinocytes in the epidermis, the collagen/elastin fibers in the
      dermal layer and the cartilage in the subcutaneous layer. The ability to non
      invasively acquire 3D structures of these tissue components may find application
      in areas such as non-invasive diagnosis of skin cancer and the study of wound
      healing processes.

PMID- 19384380
TI  - Three-dimensional confocal microscopy of the living in situ rabbit cornea.
AB  - Three-dimensional confocal microscopy of a living in situ rabbit cornea, in a
      freshly excised eye, is demonstrated in two movie loops. A specimen chamber for
      the eye was designed and constructed to maintain the unstained, unfixed, in situ
      cornea in a viable physiological state during data acquisition. The 400 micron
      thick, transparent, cornea has been optically sectioned into 365 sections using a
      laser scanning confocal microscope. A high numerical aperture, water immersion
      microscope objective minimized the spherical aberrations which would occur with
      the use of an oil immersion objective. Depth dependent light attenuation due to
      absorption and scatter within the specimen was manually compensated at each
      sampled section. Isometric sampling resulted in near-cubic voxels which
      compensated for the reduced microscopic resolution in the z-axis as compared to x
      and y- resolution.

PMID- 19384381
TI  - Three-dimensional confocal microscopy of the human optic nerve in vivo.
AB  - A scanning laser confocal microscope was used to visualize the human fundus (the
      back portion of the eyeball, as seen by means of the ophthalmoscope) in vivo from
      near the retinal surface to deep within the optic nerve head. Thirty two optical
      sections based on reflected light were acquired, digitized and aligned to
      compensate for small eye movements. The registered stack of optical sections was
      reconstructed with three-dimensional volume rendering software and presented as a
      movie. The three-dimensional rendering presents a new technique to view the optic
      nerve. This technique is clinically important since morphological changes of the
      lamina cribrosa of the optic nerve may be involved in glaucoma.

PMID- 19384382
TI  - Dispersion-controlled hollow core fiber for phase matched harmonic generation.
AB  - We describe theoretically the performance of a new design for quasi-phase matched
      harmonic generation in a gas medium. A hollow core fiber in which thick glass
      plates are periodically introduced allows good phase control of the fundamental
      light. The generated x-rays are transmitted throught small holes in the plates.
      An increase of the harmonic yield of up to three orders of magnitude is predicted
      as a result of the structure. This esign can be considered as a phase-locked
      travelling-wave x-ray laser.

PMID- 19384383
TI  - Ultrafast pulse shaping: amplification and characterization.
AB  - We demonstrate high-resolution amplified pulse shaping using an acousto-optic
      modulator (AOM) at a center-wavelength of 795nm. The output pulses have energy of
      200mJ/pulse and a transform-limited pulsewidth of 150fs. A spectral modulation of
      over 40 features is achieved in a single pulse. We characterize the pulses using
      the STRUT (Spectrally and Temporally Resolved Upconversion Technique). Using
      predistortion techniques, we demonstrate that the pulses can be shaped in
      amplitude and phase. We create a complex pulse shape with hyperbolic secant
      amplitude and hyperbolic tangent frequency sweep, which is useful for
      applications in adiabatic rapid passage experiments.

PMID- 19384384
TI  - Laser modulated scattering as a nondestructive evaluation tool for defect
      inspection in optical materials for high power laser applications.
AB  - Laser modulated scattering (LMS) is introduced as a tool for defect inspection
      and characterization of optical materials for high power laser applications. LMS
      is a scatter sensitive version of the well-known photothermal microscopy
      techniques. Because only the defects of a super-polished optic generate a
      scattering signal, the technique is essentially a method for dark-field
      photothermal microscopy. Experimental results show that the technique (1)
      measures the local absorption properties of defects, contamination, and laser
      damage sites; (2) when used in conjunction with DC scattering, can differentiate
      between absorbing and non-absorbing defects; and (3) detects thermal transport
      inhomogeneities.

PMID- 19384385
TI  - Introduction.
AB  - The study of wave interactions in periodic structures has a rich history that
      dates from the early days of solid-state physics through the development of
      coupled-wave theory. Nonlinear optics, including the physics of optical solitons,
      is a newer discipline that is steadily finding applications in laser engineering,
      communications, medicine, and many other fields. The combined study, that of
      nonlinear optical interactions in periodic structures, has been a significant
      area of study during the 1980's and 1990's and is the subject of this focus issue
      of Optics Express. The papers included in this issue represent invited
      submissions from research groups known to be active in theoretical and
      experimental studies of the nonlinear optics of periodic structures. Many of the
      papers in this special issue were originally presented as invited papers at the
      Workshop on Novel Solitons and Nonlinear Periodic Structures held in Victoria,
      Canada, in April 1998.

PMID- 19384386
TI  - Bragg solitons and optical switching in nonlinear periodic structures: an
      historical perspective.
AB  - A brief historical narrative of the study of Bragg solitons and optical switching
      in nonlinear periodic structures is presented, beginning with the first
      theoretical predictions in the late 1970s up to and including several recent
      experimental demonstrations of optical switching and nonlinear pulse propagation
      in these structures.

PMID- 19384387
TI  - Parametric gap solitons in quadratic media.
AB  - Localized energy states such as two-color gap solitons are theoretically and
      numerically predicted in a periodic structure in the presence of a frequency
      doubling nonlinearity. These parametric solitons exhibit appealing features as
      compared to the Kerr case. Novel erects such as merging and all-optical buffering
      are envisaged.

PMID- 19384388
TI  - Propagation through apodized gratings.
AB  - It is shown that light propagation in an apodized fiber Bragg grating with a Kerr
      nonlinearity approximately obeys a nonlinear Schr"odinger-like equation, but with
      extra terms because the eigenstates of the grating vary with position. It is
      shown that propagation through such a grating leads to field enhancement, and to
      a nontrivial phase shift; an approximate expression for the reflectivity is also
      found.

PMID- 19384389
TI  - High-repetition-rate soliton-train generation using fiber Bragg gratings.
AB  - We propose a high-repetition-rate soliton-train source based on adiabatic
      compression of a dual-frequency optical signal in nonuniform fiber Bragg
      gratings. As the signal propagates through the grating, it is reshaped into a
      train of Bragg solitons whose repetition rate is predetermined by the frequency
      of initial sinusoidal modulation. We develop an approximate analytical model to
      predict the width of compressed soliton-like pulses and to provide conditions for
      adiabatic compression. We demonstrate numerically the formation of a 40-GHz train
      of 2.6-ps pulses and find that the numerical results are in good agreement with
      the predictions of our analytical model. The scheme relies on the dispersion
      provided by the grating, which can be up to six orders of magnitude larger than
      of fiber and makes it possible to reduce the fiber length significantly.

PMID- 19384390
TI  - Nonlinear pulse propagation in birefringent fiber Bragg gratings.
AB  - We present two sets of equations to describe nonlinear pulse propagation in a
      birefringent fiber Bragg grating. The first set uses a coupled-mode formalism to
      describe light in or near the photonic band gap of the grating. The second set is
      a pair of coupled nonlinear Schroedinger equations. We use these equations to
      examine viable switching experiments in the presence of birefringence. We show
      how the birefringence can both aid and hinder device applications.

PMID- 19384391
TI  - Semiconductor periodic structures for out-of-plane optical switching and Bragg
      soliton excitation.
AB  - We study out-of-plane coupling and switching in a semiconductor periodic
      waveguide structure, with attention given to both dispersion within the structure
      and impedence matching of an external wave with a guided mode. We show nanosecond
      scale optical switching and discuss the implications for Bragg soliton
      excitation.

PMID- 19384392
TI  - Low-power all-optical switching in active semiconductor chirped periodic
      structures.
AB  - We investigate the effects of spatial chirp of the built-in grating on the
      spectral range and switching power of all-optical switching in active
      semiconductor periodic structures. We show that a total linear variation in the
      grating period of as little as 0.24% nearly triples the spectral range of low
      power switching. Moreover, the upward-switching power at the onset of bistability
      is lowered by two orders of magnitude, to a value below 10 nW for typical device
      parameter values. These improvements occur for optical signals tuned to the long
      wavelength side of the stop band and propagating in the direction of increasing
      grating period. We also predict the existence of multiple bistable hystereses in
      devices with large amounts of spatial chirp.

PMID- 19384393
TI  - Nonlinear switching in fibre Bragg gratings.
AB  - We report on our recent experiments on nonlinear switching in fibre Bragg
      gratings. Using an all-fibre source we show an increase in transmission of a FBG
      from 4% to 40% at high powers. This switching is associated with the formation of
      gap solitons inside the grating. We also demonstrate an all-optical AND gate
      using polarization coupled gap solitons and the optical pushbroom.

PMID- 19384394
TI  - All-optical switching in distributed-feedback muiltiple-quantum-well waveguides.
AB  - We discuss experimental results that demonstrate all-optical switching and pulse
      routing functionality, at 1.55 um, of nonlinear multiple-quantum-well waveguides
      equipped with a Bragg grating. Basing on the nonlinear Time-Domain Beam
      Propagation Method, the switching behavior has been theoretically investigated
      using a model, developed as part of this work.

PMID- 19384395
TI  - Nonlinear pulse reflections from chirped fiber gratings.
AB  - We study the nonlinear evolution of optical pulses reflected from a chirped fiber
      grating experimentally and with numerical simulations. Over a broad range of
      grating parameters the nonlinearly reflected pulse splits into a pair of pulses
      in the range of incident pulse intensities where the transmitted pulse is a
      single narrowed pulse evolving into a fundamental soliton.

PMID- 19384396
TI  - Spatial patterns in optical parametric oscillators with spherical mirrors:
      classical and quantum effects: errata.
AB  - The correct author affiliation for K. I. Petsas, A. Gatti and L. A. Lugiato is:
      Dipartimento di Fisica dell'Universita di Milano, Istituto Nazionale per la
      Fisica della Materia, Via Celoria 16, Milano 20133, Italy.

PMID- 19384397
TI  - Introduction.
AB  - One of the greatest advantages of the ubiquitous Internet, the free and easy
      transmission of information, is also one of its greatest weaknesses, leading to
      the copying and outright theft of information. Of particular interest to the
      readers of this journal is the theft of images and videos. A content provider may
      want to publish information without having that information stolen and
      misrepresented as another's. Legally, the content provider needs to be able to
      enforce a copyright and convince an impartial arbitrator (e.g., a judge) that the
      content is his and not the other person's.

PMID- 19384398
TI  - Intellectual property protection systems and digital watermarking.
AB  - Adequate protection of digital copies of multimedia content - both audio and
      video - is a prerequisite to the distribution of this content over networks.
      Until recently digital audio and video content has been protected by its size: it
      is difficult to distribute and store without compression. Modern compression
      algorithms allow substantial bitrate reduction while maintaining high-fidelity
      reproduction. If distribution of these algorithms is controlled, cleartext
      uncompressed content is still protected by its size. However, once the
      compression algorithms are generally available cleartext content becomes
      extremely vulnerable to piracy. In this paper we explore the implications of this
      vulnerability and discuss the use of compression and watermarking in the control
      of piracy.

PMID- 19384399
TI  - Improved robust watermarking through attack characterization.
AB  - In this paper, we propose an approach to improve the performance of a broad class
      of watermarking schemes through attack characterization. Robust and reference
      watermarks are both embedded into a signal. The reference watermark is used to
      characterize any modifications of the resulting marked signal, so that the robust
      watermark can be more reliably extracted. Analysis and simulations are provided
      to demonstrate the effectiveness of the approach.

PMID- 19384400
TI  - Wavelet-based digital image watermarking.
AB  - A wavelet-based watermark casting scheme and a blind watermark retrieval
      technique are investigated in this research. An adaptive watermark casting method
      is developed to first determine significant wavelet subbands and then select a
      couple of significant wavelet coefficients in these subbands to embed watermarks.
      A blind watermark retrieval technique that can detect the embedded watermark
      without the help from the original image is proposed. Experimental results show
      that the embedded watermark is robust against various signal processing and
      compression attacks.

PMID- 19384401
TI  - Wavelet transform based watermark for digital images.
AB  - In this paper, we introduce a new multiresolution watermarking method for digital
      images. The method is based on the discrete wavelet transform (DWT). Pseudo
      random codes are added to the large coefficients at the high and middle frequency
      bands of the DWT of an image. It is shown that this method is more robust to
      proposed methods to some common image distortions, such as the wavelet transform
      based image compression, image rescaling/stretching and image halftoning.
      Moreover, the method is hierarchical.

PMID- 19384402
TI  - Image watermarking using block site selection and DCT domain constraints.
AB  - In this paper we propose an image watermarking algorithm based on constraints in
      the Discrete Cosine Transform (DCT) domain. An image watermarking algorithm has
      two stages: signature casting (embedding) and signature detection. In the first
      stage it embeds an identifying label in the image. This is recognized in the
      second stage. The proposed algorithm has two processing steps. In the first step
      certain pixel blocks are selected using a set of parameters while in the second
      step a DCT coefficient constraint is embedded in the selected blocks. Two
      different constraint rules are suggested for the parametric modification of the
      DCT frequency coefficients. The first one embeds a linear constraint among
      certain selected DCT coefficients and the second defines circular detection
      regions according to the given parameters. The watermarks cast by the proposed
      algorithm are resistant to JPEG compression and filtering.

PMID- 19384403
TI  - Experimental observation of interfering Bessel beams.
AB  - We experimentally verified the interference resulting of the superposition of two
      Bessel beams propagating in free space and showed for first time the self imaging
      effect using nondiffracting beams. Our results are supported by numerical
      simulations and possible applications are discussed.

PMID- 19384404
TI  - Four wave mixing in the scattering of Bose-Einstein condensates.
AB  - The nonlinear coupling term in the Gross-Pitiaevski equation which describes a
      Bose-Einstein condensate (BEC) can cause four- wave mixing (4WM) if three BEC
      wavepackets with momenta k1, k2, and k3 interact. The interaction will produce a
      fourth wavepacket with momentum k4 = k1 + k2. We study this process using
      numerical models and suggest that experiments are feasible. Conservation of
      energy and momentum have different consequences for 4WM with massive particles
      than in the nonlinear optics case because of the different energy-momentum
      dispersion relations.

PMID- 19384407
TI  - Small-molecule activators of insulin-degrading enzyme discovered through high
      throughput compound screening.
AB  - BACKGROUND: Hypocatabolism of the amyloid beta-protein (Abeta) by insulin
      degrading enzyme (IDE) is implicated in the pathogenesis of Alzheimer disease
      (AD), making pharmacological activation of IDE an attractive therapeutic
      strategy. However, it has not been established whether the proteolytic activity
      of IDE can be enhanced by drug-like compounds. METHODOLOGY/PRINCIPAL FINDINGS:
      Based on the finding that ATP and other nucleotide polyphosphates modulate IDE
      activity at physiological concentrations, we conducted parallel high-throughput
      screening campaigns in the absence or presence of ATP and identified two
      compounds--designated Ia1 and Ia2--that significantly stimulate IDE proteolytic
      activity. Both compounds were found to interfere with the crosslinking of a
      photoaffinity ATP analogue to IDE, suggesting that they interact with a bona fide
      ATP-binding domain within IDE. Unexpectedly, we observed highly synergistic
      activation effects when the activity of Ia1 or Ia2 was tested in the presence of
      ATP, a finding that has implications for the mechanisms underlying ATP-mediated
      activation of IDE. Notably, Ia1 and Ia2 activated the degradation of Abeta by
      approximately 700% and approximately 400%, respectively, albeit only when Abeta
      was presented in a mixture also containing shorter substrates.
      CONCLUSIONS/SIGNIFICANCE: This study describes the first examples of synthetic
      small-molecule activators of IDE, showing that pharmacological activation of this
      important protease with drug-like compounds is achievable. These novel activators
      help to establish the putative ATP-binding domain as a key modulator of IDE
      proteolytic activity and offer new insights into the modulatory action of ATP.
      Several larger lessons abstracted from this screen will help inform the design of
      future screening campaigns and facilitate the eventual development of IDE
      activators with therapeutic utility.

PMID- 19384408
TI  - Rpb1 sumoylation in response to UV radiation or transcriptional impairment in
      yeast.
AB  - Covalent modifications of proteins by ubiquitin and the Small Ubiquitin-like
      MOdifier (SUMO) have been revealed to be involved in a plethora of cellular
      processes, including transcription, DNA repair and DNA damage responses. It has
      been well known that in response to DNA damage that blocks transcription
      elongation, Rpb1, the largest subunit of RNA polymerase II (Pol II), is
      ubiquitylated and subsequently degraded in mammalian and yeast cells. However, it
      is still an enigma regarding how Pol II responds to damaged DNA and conveys
      signal(s) for DNA damage-related cellular processes. We found that Rpb1 is also
      sumoylated in yeast cells upon UV radiation or impairment of transcription
      elongation, and this modification is independent of DNA damage checkpoint
      activation. Ubc9, an E2 SUMO conjugase, and Siz1, an E3 SUMO ligase, play
      important roles in Rpb1 sumoylation. K1487, which is located in the acidic linker
      region between the C-terminal domain and the globular domain of Rpb1, is the
      major sumoylation site. Rpb1 sumoylation is not affected by its ubiquitylation,
      and vice versa, indicating that the two processes do not crosstalk. Abolishment
      of Rpb1 sumoylation at K1487 does not affect transcription elongation or
      transcription coupled repair (TCR) of UV-induced DNA damage. However, deficiency
      in TCR enhances UV-induced Rpb1 sumoylation, presumably due to the persistence of
      transcription-blocking DNA lesions in the transcribed strand of a gene.
      Remarkably, abolishment of Rpb1 sumoylation at K1487 causes enhanced and
      prolonged UV-induced phosphorylation of Rad53, especially in TCR-deficient cells,
      suggesting that the sumoylation plays a role in restraining the DNA damage
      checkpoint response caused by transcription-blocking lesions. Our results
      demonstrate a novel covalent modification of Rpb1 in response to UV induced DNA
      damage or transcriptional impairment, and unravel an important link between the
      modification and the DNA damage checkpoint response.

PMID- 19384409
TI  - N- and C-terminal domains of the calcium binding protein EhCaBP1 of the parasite
      Entamoeba histolytica display distinct functions.
AB  - Entamoeba histolytica, a protozoan parasite, is the causative agent of
      amoebiasis, and calcium signaling is thought to be involved in amoebic
      pathogenesis. EhCaBP1, a Ca(2+) binding protein of E. histolytica, is essential
      for parasite growth. High resolution crystal structure of EhCaBP1 suggested an
      unusual arrangement of the EF-hand domains in the N-terminal part of the
      structure, while C-terminal part of the protein was not traced. The structure
      revealed a trimer with amino terminal domains of the three molecules interacting
      in a head-to-tail manner forming an assembled domain at the interface with EF1
      and EF2 motifs of different molecules coming close to each other. In order to
      understand the specific roles of the two domains of EhCaBP1, the molecule was
      divided into two halves, and each half was separately expressed. The domains were
      characterized with respect to their structure, as well as specific functional
      features, such as ability to activate kinase and bind actin. The domains were
      also expressed in E. histolytica cells along with green fluorescent protein. The
      results suggest that the N-terminal domain retains some of the properties, such
      as localization in phagocytic cups and activation of kinase. Crystal structure of
      EhCaBP1 with Phenylalanine revealed that the assembled domains, which are similar
      to Calmodulin N-terminal domain, bind to Phenylalanine revealing the binding mode
      to the target proteins. The C-terminal domain did not show any of the activities
      tested. However, over-expression in amebic cells led to a dominant negative
      phenotype. The results suggest that the two domains of EhCaBP1 are functionally
      and structurally different from each other. Both the domains are required for
      structural stability and full range of functional diversity.

PMID- 19384410
TI  - Consumers control diversity and functioning of a natural marine ecosystem.
AB  - BACKGROUND: Our understanding of the functional consequences of changes in
      biodiversity has been hampered by several limitations of previous work, including
      limited attention to trophic interactions, a focus on species richness rather
      than evenness, and the use of artificially assembled communities. METHODOLOGY AND
      PRINCIPAL FINDINGS: In this study, we manipulated the density of an herbivorous
      snail in natural tide pools and allowed seaweed communities to assemble in an
      ecologically relevant and non-random manner. Seaweed species evenness and biomass
      specific primary productivity (mg O(2) h(-1) g(-1)) were higher in tide pools
      with snails because snails preferentially consumed an otherwise dominant seaweed
      species that can reduce biomass-specific productivity rates of algal assemblages.
      Although snails reduced overall seaweed biomass in tide pools, they did not
      affect gross primary productivity at the scale of tide pools (mg O(2) h(-1) pool(
      1) or mg O(2) h(-1) m(-2)) because of the enhanced biomass-specific productivity
      associated with grazer-mediated increases in algal evenness. SIGNIFICANCE: Our
      results suggest that increased attention to trophic interactions, diversity
      measures other than richness, and particularly the effects of consumers on
      evenness and primary productivity, will improve our understanding of the
      relationship between diversity and ecosystem functioning and allow more effective
      links between experimental results and real-world changes in biodiversity.

PMID- 19384411
TI  - Histoplasma capsulatum encodes a dipeptidyl peptidase active against the
      mammalian immunoregulatory peptide, substance P.
AB  - The pathogenic fungus Histoplasma capsulatum secretes dipeptidyl peptidase (Dpp)
      IV enzyme activity and has two putative DPPIV homologs (HcDPPIVA and HcDPPIVB).
      We previously showed that HcDPPIVB is the gene responsible for the majority of
      secreted DppIV activity in H. capsulatum culture supernatant, while we could not
      detect any functional contribution from HcDPPIVA. In order to determine whether
      HcDPPIVA encodes a functional DppIV enzyme, we expressed HcDPPIVA in Pichia
      pastoris and purified the recombinant protein. The recombinant enzyme cleaved
      synthetic DppIV substrates and had similar biochemical properties to other
      described DppIV enzymes, with temperature and pH optima of 42 degrees C and 8,
      respectively. Recombinant HcDppIVA cleaved the host immunoregulatory peptide
      substance P, indicating the enzyme has the potential to affect the immune
      response during infection. Expression of HcDPPIVA under heterologous regulatory
      sequences in H. capsulatum resulted in increased secreted DppIV activity,
      indicating that the encoded protein can be expressed and secreted by its native
      organism. However, HcDPPIVA was not required for virulence in a murine model of
      histoplasmosis. This work reports a fungal enzyme that can function to cleave the
      immunomodulatory host peptide substance P.

PMID- 19384412
TI  - Assessing biofuel crop invasiveness: a case study.
AB  - BACKGROUND: There is widespread interest in biofuel crops as a solution to the
      world's energy needs, particularly in light of concerns over greenhouse-gas
      emissions. Despite reservations about their adverse environmental impacts, no
      attempt has been made to quantify actual, relative or potential invasiveness of
      terrestrial biofuel crops at an appropriate regional or international scale, and
      their planting continues to be largely unregulated. METHODOLOGY/PRINCIPAL
      FINDINGS: Using a widely accepted weed risk assessment system, we analyzed a
      comprehensive list of regionally suitable biofuel crops to show that seventy
      percent have a high risk of becoming invasive versus one-quarter of non-biofuel
      plant species and are two to four times more likely to establish wild populations
      locally or be invasive in Hawaii or in other locations with a similar climate.
      CONCLUSIONS/SIGNIFICANCE: Because of climatic and ecological similarities,
      predictions of biofuel crop invasiveness in Hawaii are applicable to other
      vulnerable island and subtropical ecosystems worldwide. We demonstrate the
      utility of an accessible and scientifically proven risk assessment protocol that
      allows users to predict if introduced species will become invasive in their
      region of interest. Other evidence supports the contention that propagule
      pressure created by extensive plantings will exacerbate invasions, a scenario
      expected with large-scale biofuel crop cultivation. Proactive measures, such as
      risk assessments, should be employed to predict invasion risks, which could then
      be mitigated via implementation of appropriate planting policies and adoption of
      the "polluter-pays" principle.

PMID- 19384413
TI  - Hair cell bundles: flexoelectric motors of the inner ear.
AB  - Microvilli (stereocilia) projecting from the apex of hair cells in the inner ear
      are actively motile structures that feed energy into the vibration of the inner
      ear and enhance sensitivity to sound. The biophysical mechanism underlying the
      hair bundle motor is unknown. In this study, we examined a membrane flexoelectric
      origin for active movements in stereocilia and conclude that it is likely to be
      an important contributor to mechanical power output by hair bundles. We
      formulated a realistic biophysical model of stereocilia incorporating stereocilia
      dimensions, the known flexoelectric coefficient of lipid membranes, mechanical
      compliance, and fluid drag. Electrical power enters the stereocilia through
      displacement sensitive ion channels and, due to the small diameter of
      stereocilia, is converted to useful mechanical power output by flexoelectricity.
      This motor augments molecular motors associated with the mechanosensitive
      apparatus itself that have been described previously. The model reveals
      stereocilia to be highly efficient and fast flexoelectric motors that capture the
      energy in the extracellular electro-chemical potential of the inner ear to
      generate mechanical power output. The power analysis provides an explanation for
      the correlation between stereocilia height and the tonotopic organization of
      hearing organs. Further, results suggest that flexoelectricity may be essential
      to the exquisite sensitivity and frequency selectivity of non-mammalian hearing
      organs at high auditory frequencies, and may contribute to the "cochlear
      amplifier" in mammals.

PMID- 19384414
TI  - Auditory-visual object recognition time suggests specific processing for animal
      sounds.
AB  - BACKGROUND: Recognizing an object requires binding together several cues, which
      may be distributed across different sensory modalities, and ignoring competing
      information originating from other objects. In addition, knowledge of the
      semantic category of an object is fundamental to determine how we should react to
      it. Here we investigate the role of semantic categories in the processing of
      auditory-visual objects. METHODOLOGY/FINDINGS: We used an auditory-visual object
      recognition task (go/no-go paradigm). We compared recognition times for two
      categories: a biologically relevant one (animals) and a non-biologically relevant
      one (means of transport). Participants were asked to react as fast as possible to
      target objects, presented in the visual and/or the auditory modality, and to
      withhold their response for distractor objects. A first main finding was that,
      when participants were presented with unimodal or bimodal congruent stimuli (an
      image and a sound from the same object), similar reaction times were observed for
      all object categories. Thus, there was no advantage in the speed of recognition
      for biologically relevant compared to non-biologically relevant objects. A second
      finding was that, in the presence of a biologically relevant auditory distractor,
      the processing of a target object was slowed down, whether or not it was itself
      biologically relevant. It seems impossible to effectively ignore an animal sound,
      even when it is irrelevant to the task. CONCLUSIONS/SIGNIFICANCE: These results
      suggest a specific and mandatory processing of animal sounds, possibly due to
      phylogenetic memory and consistent with the idea that hearing is particularly
      efficient as an alerting sense. They also highlight the importance of taking into
      account the auditory modality when investigating the way object concepts of
      biologically relevant categories are stored and retrieved.

PMID- 19384415
TI  - Genetic structures of copy number variants revealed by genotyping single sperm.
AB  - BACKGROUND: Copy number variants (CNVs) occupy a significant portion of the human
      genome and may have important roles in meiotic recombination, human genome
      evolution and gene expression. Many genetic diseases may be underlain by CNVs.
      However, because of the presence of their multiple copies, variability in copy
      numbers and the diploidy of the human genome, detailed genetic structure of CNVs
      cannot be readily studied by available techniques. METHODOLOGY/PRINCIPAL
      FINDINGS: Single sperm samples were used as the primary subjects for the study so
      that CNV haplotypes in the sperm donors could be studied individually. Forty
      eight CNVs characterized in a previous study were analyzed using a microarray
      based high-throughput genotyping method after multiplex amplification. Seventeen
      single nucleotide polymorphisms (SNPs) were also included as controls. Two single
      base variants, either allelic or paralogous, could be discriminated for all
      markers. Microarray data were used to resolve SNP alleles and CNV haplotypes, to
      quantitatively assess the numbers and compositions of the paralogous segments in
      each CNV haplotype. CONCLUSIONS/SIGNIFICANCE: This is the first study of the
      genetic structure of CNVs on a large scale. Resulting information may help
      understand evolution of the human genome, gain insight into many genetic
      processes, and discriminate between CNVs and SNPs. The highly sensitive high
      throughput experimental system with haploid sperm samples as subjects may be used
      to facilitate detailed large-scale CNV analysis.

PMID- 19384416
TI  - Rare species are valued big time.
AB  - BACKGROUND: It has recently been postulated that the value humans place on rarity
      could cause the extinction of rare species. This is because people are willing to
      pay the high costs of exploiting the last individuals. Many hobbies, such as
      ecotourism or the keeping of exotic pets may cause this effect--known as the
      anthropogenic Allee effect. However, the entire theory relies on the insofar
      undemonstrated assumption that people do value rarity. METHODOLOGY/PRINCIPAL
      FINDINGS: In order to quantify how much people valued rare species relative to
      common ones, we created online slideshows of photographs of either rare or common
      species on an Internet web site. The slideshow with photographs of rare species
      attracted more visitors, and visitors spent, in general, more time waiting to
      view it. CONCLUSIONS/SIGNIFICANCE: We provide evidence that people value rare
      more than common species. As we did not target consumers of a specific market,
      this finding suggests that the anthropogenic Allee effect is likely be driven by
      a large part of the population. Given the substantial participation in our online
      experiment, we highlight the potential of the world wide web resource as a tool
      for conservation action. However, the evidence presented here that the general
      public value rare species, combined with the assumption that anthropogenic Allee
      effect is operating, implies that conservationists should be prudent when using
      rarity to promote conservation.

PMID- 19384417
TI  - Molecular identification and expression analysis of filaggrin-2, a member of the
      S100 fused-type protein family.
AB  - Genes of the S100 fused-type protein (SFTP) family are clustered within the
      epidermal differentiation complex and encode essential components that maintain
      epithelial homeostasis and barrier functions. Recent genetic studies have shown
      that mutations within the gene encoding the SFTP filaggrin cause ichthyosis
      vulgaris and are major predisposing factors for atopic dermatitis. As a vital
      component of healthy skin, filaggrin is also a precursor of natural moisturizing
      factors. Here we present the discovery of a member of this family, designated as
      filaggrin-2 (FLG2) that is expressed in human skin. The FLG2 gene encodes a
      histidine- and glutamine-rich protein of approximately 248 kDa, which shares
      common structural features with other SFTP members, in particular filaggrin. We
      found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis
      and placenta. In cultured primary keratinocytes, FLG2 mRNA expression displayed
      almost the same kinetics as that of filaggrin following Ca(2+) stimulation,
      suggesting an important role in molecular regulation of epidermal terminal
      differentiation. We provide evidences that like filaggrin, FLG2 is initially
      expressed by upper granular cells, proteolytically processed and deposited in the
      stratum granulosum and stratum corneum (SC) layers of normal epidermis. Thus,
      FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the
      formation of the epidermal barrier, protecting the skin from environmental
      insults and the escape of moisture by offering precursors of natural moisturizing
      factors.

PMID- 19384418
TI  - Consequences of the timing of menarche on female adolescent sleep phase
      preference.
AB  - Most parents experience their children's puberty as a dramatic change in family
      life. This is not surprising considering the dynamics of physical and
      psychosocial maturation which occur during adolescence. A reasonable question,
      particularly from the parents' perspective, is: when does this vibrant episode
      end and adulthood finally start? The aim of the present study was to assess the
      relationship between puberty and the changes in sleep phase preferences during
      female maturation and adulthood by a cross-sectional survey. The results from
      1'187 females aged 5 to 51 years based on self-report measures of sleep
      preferences on weekdays and on free days as well as the occurrence of menarche,
      show that in contrast to prepubertal children, adolescent females exhibit a
      striking progression in delaying their sleep phase preference until 5 years after
      menarche. Thereafter, the sleep phase preference switches to advancing. The
      current study provides evidence that a clear shift in sleep-wake cycles
      temporally linked to menarche heralds the beginning of "adult-like" sleep-wake
      behaviour in women and can be used as a (chrono)biological marker for the onset
      of adulthood.

PMID- 19384419
TI  - The ordered extension of pseudopodia by amoeboid cells in the absence of external
      cues.
AB  - Eukaryotic cells extend pseudopodia for movement. In the absence of external
      cues, cells move in random directions, but with a strong element of persistence
      that keeps them moving in the same direction Persistence allows cells to disperse
      over larger areas and is instrumental to enter new environments where spatial
      cues can lead the cell. Here we explore cell movement by analyzing the direction,
      size and timing of approximately 2000 pseudopodia that are extended by
      Dictyostelium cells. The results show that pseudpopod are extended perpendicular
      to the surface curvature at the place where they emerge. The location of new
      pseudopods is not random but highly ordered. Two types of pseudopodia may be
      formed: frequent splitting of an existing pseudopod, or the occasional extension
      of a de novo pseudopod at regions devoid of recent pseudopod activity. Split
      pseudopodia are extended at approximately 60 degrees relative to the previous
      pseudopod, mostly as alternating Right/Left/Right steps leading to relatively
      straight zigzag runs. De novo pseudopodia are extended in nearly random
      directions thereby interrupting the zigzag runs. Persistence of cell movement is
      based on the ratio of split versus de novo pseudopodia. We identify PLA2 and cGMP
      signaling pathways that modulate this ratio of splitting and de novo pseudopodia,
      and thereby regulate the dispersal of cells. The observed ordered extension of
      pseudopodia in the absence of external cues provides a fundamental insight into
      the coordinated movement of cells, and might form the basis for movement that is
      directed by internal or external cues.

PMID- 19384420
TI  - Integration of gravitational torques in cerebellar pathways allows for the
      dynamic inverse computation of vertical pointing movements of a robot arm.
AB  - BACKGROUND: Several authors suggested that gravitational forces are centrally
      represented in the brain for planning, control and sensorimotor predictions of
      movements. Furthermore, some studies proposed that the cerebellum computes the
      inverse dynamics (internal inverse model) whereas others suggested that it
      computes sensorimotor predictions (internal forward model). METHODOLOGY/PRINCIPAL
      FINDINGS: This study proposes a model of cerebellar pathways deduced from both
      biological and physical constraints. The model learns the dynamic inverse
      computation of the effect of gravitational torques from its sensorimotor
      predictions without calculating an explicit inverse computation. By using
      supervised learning, this model learns to control an anthropomorphic robot arm
      actuated by two antagonists McKibben artificial muscles. This was achieved by
      using internal parallel feedback loops containing neural networks which
      anticipate the sensorimotor consequences of the neural commands. The artificial
      neural networks architecture was similar to the large-scale connectivity of the
      cerebellar cortex. Movements in the sagittal plane were performed during three
      sessions combining different initial positions, amplitudes and directions of
      movements to vary the effects of the gravitational torques applied to the robotic
      arm. The results show that this model acquired an internal representation of the
      gravitational effects during vertical arm pointing movements.
      CONCLUSIONS/SIGNIFICANCE: This is consistent with the proposal that the
      cerebellar cortex contains an internal representation of gravitational torques
      which is encoded through a learning process. Furthermore, this model suggests
      that the cerebellum performs the inverse dynamics computation based on
      sensorimotor predictions. This highlights the importance of sensorimotor
      predictions of gravitational torques acting on upper limb movements performed in
      the gravitational field.

PMID- 19384421
TI  - Perturbing dynamin reveals potent effects on the Drosophila circadian clock.
AB  - BACKGROUND: Transcriptional feedback loops are central to circadian clock
      function. However, the role of neural activity and membrane events in molecular
      rhythms in the fruit fly Drosophila is unclear. To address this question, we
      expressed a temperature-sensitive, dominant negative allele of the fly homolog of
      dynamin called shibire(ts1) (shi(ts1)), an active component in membrane vesicle
      scission. PRINCIPAL FINDINGS: Broad expression in clock cells resulted in
      unexpectedly long, robust periods (>28 hours) comparable to perturbation of core
      clock components, suggesting an unappreciated role of membrane dynamics in
      setting period. Expression in the pacemaker lateral ventral neurons (LNv) was
      necessary and sufficient for this effect. Manipulation of other endocytic
      components exacerbated shi(ts1)'s behavioral effects, suggesting its mechanism is
      specific to endocytic regulation. PKA overexpression rescued period effects
      suggesting shi(ts1) may downregulate PKA pathways. Levels of the clock component
      PERIOD were reduced in the shi(ts1)-expressing pacemaker small LNv of flies held
      at a fully restrictive temperature (29 degrees C). Less restrictive conditions
      (25 degrees C) delayed cycling proportional to observed behavioral changes.
      Levels of the neuropeptide PIGMENT-DISPERSING FACTOR (PDF), the only known LNv
      neurotransmitter, were also reduced, but PERIOD cycling was still delayed in
      flies lacking PDF, implicating a PDF-independent process. Further, shi(ts1)
      expression in the eye also results in reduced PER protein and per and vri
      transcript levels, suggesting that shibire-dependent signaling extends to
      peripheral clocks. The level of nuclear CLK, transcriptional activator of many
      core clock genes, is also reduced in shi(ts1) flies, and Clk overexpression
      suppresses the period-altering effects of shi(ts1). CONCLUSIONS: We propose that
      membrane protein turnover through endocytic regulation of PKA pathways modulates
      the core clock by altering CLK levels and/or activity. These results suggest an
      important role for membrane scission in setting circadian period.

PMID- 19384422
TI  - Impact of pretreated Switchgrass and biomass carbohydrates on Clostridium
      thermocellum ATCC 27405 cellulosome composition: a quantitative proteomic
      analysis.
AB  - BACKGROUND: Economic feasibility and sustainability of lignocellulosic ethanol
      production requires the development of robust microorganisms that can efficiently
      degrade and convert plant biomass to ethanol. The anaerobic thermophilic
      bacterium Clostridium thermocellum is a candidate microorganism as it is capable
      of hydrolyzing cellulose and fermenting the hydrolysis products to ethanol and
      other metabolites. C. thermocellum achieves efficient cellulose hydrolysis using
      multiprotein extracellular enzymatic complexes, termed cellulosomes.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used quantitative proteomics
      (multidimensional LC-MS/MS and (15)N-metabolic labeling) to measure relative
      changes in levels of cellulosomal subunit proteins (per CipA scaffoldin basis)
      when C. thermocellum ATCC 27405 was grown on a variety of carbon sources [dilute
      acid pretreated switchgrass, cellobiose, amorphous cellulose, crystalline
      cellulose (Avicel) and combinations of crystalline cellulose with pectin or xylan
      or both]. Cellulosome samples isolated from cultures grown on these carbon
      sources were compared to (15)N labeled cellulosome samples isolated from
      crystalline cellulose-grown cultures. In total from all samples, proteomic
      analysis identified 59 dockerin- and 8 cohesin-module containing components,
      including 16 previously undetected cellulosomal subunits. Many cellulosomal
      components showed differential protein abundance in the presence of non-cellulose
      substrates in the growth medium. Cellulosome samples from amorphous cellulose,
      cellobiose and pretreated switchgrass-grown cultures displayed the most distinct
      differences in composition as compared to cellulosome samples from crystalline
      cellulose-grown cultures. While Glycoside Hydrolase Family 9 enzymes showed
      increased levels in the presence of crystalline cellulose, and pretreated
      switchgrass, in particular, GH5 enzymes showed increased levels in response to
      the presence of cellulose in general, amorphous or crystalline.
      CONCLUSIONS/SIGNIFICANCE: Overall, the quantitative results suggest a coordinated
      substrate-specific regulation of cellulosomal subunit composition in C.
      thermocellum to better suit the organism's needs for growth under different
      conditions. To date, this study provides the most comprehensive comparison of
      cellulosomal compositional changes in C. thermocellum in response to different
      carbon sources. Such studies are vital to engineering a strain that is best
      suited to grow on specific substrates of interest and provide the building blocks
      for constructing designer cellulosomes with tailored enzyme composition for
      industrial ethanol production.

PMID- 19384423
TI  - Doom and boom on a resilient reef: climate change, algal overgrowth and coral
      recovery.
AB  - BACKGROUND: Coral reefs around the world are experiencing large-scale
      degradation, largely due to global climate change, overfishing, diseases and
      eutrophication. Climate change models suggest increasing frequency and severity
      of warming-induced coral bleaching events, with consequent increases in coral
      mortality and algal overgrowth. Critically, the recovery of damaged reefs will
      depend on the reversibility of seaweed blooms, generally considered to depend on
      grazing of the seaweed, and replenishment of corals by larvae that successfully
      recruit to damaged reefs. These processes usually take years to decades to bring
      a reef back to coral dominance. METHODOLOGY/PRINCIPAL FINDINGS: In 2006, mass
      bleaching of corals on inshore reefs of the Great Barrier Reef caused high coral
      mortality. Here we show that this coral mortality was followed by an
      unprecedented bloom of a single species of unpalatable seaweed (Lobophora
      variegata), colonizing dead coral skeletons, but that corals on these reefs
      recovered dramatically, in less than a year. Unexpectedly, this rapid reversal
      did not involve reestablishment of corals by recruitment of coral larvae, as
      often assumed, but depended on several ecological mechanisms previously
      underestimated. CONCLUSIONS/SIGNIFICANCE: These mechanisms of ecological recovery
      included rapid regeneration rates of remnant coral tissue, very high competitive
      ability of the corals allowing them to out-compete the seaweed, a natural
      seasonal decline in the particular species of dominant seaweed, and an effective
      marine protected area system. Our study provides a key example of the doom and
      boom of a highly resilient reef, and new insights into the variability and
      mechanisms of reef resilience under rapid climate change.

PMID- 19384424
TI  - Protandim, a fundamentally new antioxidant approach in chemoprevention using
      mouse two-stage skin carcinogenesis as a model.
AB  - Oxidative stress is an important contributor to cancer development. Consistent
      with that, antioxidant enzymes have been demonstrated to suppress tumorigenesis
      when being elevated both in vitro and in vivo, making induction of these enzymes
      a more potent approach for cancer prevention. Protandim, a well-defined
      combination of widely studied medicinal plants, has been shown to induce
      superoxide dismutase (SOD) and catalase activities and reduce superoxide
      generation and lipid peroxidation in healthy human subjects. To investigate
      whether Protandim can suppress tumor formation by a dietary approach, a two-stage
      mouse skin carcinogenesis study was performed. At the end of the study, the mice
      on a Protandim-containing basal diet had similar body weight compared with those
      on the basal diet, which indicated no overt toxicity by Protandim. After three
      weeks on the diets, there was a significant increase in the expression levels of
      SOD and catalase, in addition to the increases in SOD activities. Importantly, at
      the end of the carcinogenesis study, both skin tumor incidence and multiplicity
      were reduced in the mice on the Protandim diet by 33% and 57% respectively,
      compared with those on basal diet. Biochemical and histological studies revealed
      that the Protandim diet suppressed tumor promoter-induced oxidative stress
      (evidenced by reduction of protein carbonyl levels), cell proliferation
      (evidenced by reduction of skin hyperplasia and suppression of PKC/JNK/Jun
      pathway), and inflammation (evidenced by reduction of ICAM-1/VCAM-1 expression,
      NF-kappaB binding activity, and nuclear p65/p50 levels). Overall, induction of
      antioxidant enzymes by Protandim may serve as a practical and potent approach for
      cancer prevention.

PMID- 19384425
TI  - Implantable Biosensors for Real-time Strain and Pressure Monitoring.
AB  - Implantable biosensors were developed for real-time monitoring of pressure and
      strain in the human body. The sensor, which was wireless and passive, consisted
      of a soft magnetic material and a permanent magnet. When exposed to a low
      frequency AC magnetic field, the soft magnetic material generated secondary
      magnetic fields that also included the higher-order harmonic modes. Parameters of
      interest were determined by measuring the changes in the pattern of these higher
      order harmonic fields, which was achieved by changing the intensity of a DC
      magnetic field generated by a permanent magnet. The DC magnetic field, or the
      biasing field, was altered by changing the separation distance between the soft
      magnetic material and the permanent magnet. For pressure monitoring, the
      permanent magnet was placed on the membrane of an airtight chamber. Changes in
      the ambient pressure deflected the membrane, altering the separation distance
      between the two magnetic elements and thus the higher-order harmonic fields.
      Similarly, the soft magnetic material and the permanent magnet were separated by
      a flexible substrate in the stress/strain sensor. Compressive and tensile forces
      flexed the substrate, changing the separation distance between the two elements
      and the higher-order harmonic fields. In the current study, both stress/strain
      and pressure sensors were fabricated and characterized. Good stability, linearity
      and repeatability of the sensors were demonstrated. This passive and wireless
      sensor technology may be useful for long term detection of physical quantities
      within the human body as a part of treatment assessment, disease diagnosis, or
      detection of biomedical implant failures.

PMID- 19384427
TI  - Mapping Nucleotide Sequences that Encode Complex Binary Disease Traits with
      HapMap.
AB  - Detecting the patterns of DNA sequence variants across the human genome is a
      crucial step for unraveling the genetic basis of complex human diseases. The
      human HapMap constructed by single nucleotide polymorphisms (SNPs) provides
      efficient sequence variation information that can speed up the discovery of genes
      related to common diseases. In this article, we present a generalized linear
      model for identifying specific nucleotide variants that encode complex human
      diseases. A novel approach is derived to group haplotypes to form composite
      diplotypes, which largely reduces the model degrees of freedom for an association
      test and hence increases the power when multiple SNP markers are involved. An
      efficient two-stage estimation procedure based on the expectation-maximization
      (EM) algorithm is derived to estimate parameters. Non-genetic environmental or
      clinical risk factors can also be fitted into the model. Computer simulations
      show that our model has reasonable power and type I error rate with appropriate
      sample size. It is also suggested through simulations that a balanced design with
      approximately equal number of cases and controls should be preferred to maintain
      small estimation bias and reasonable testing power. To illustrate the utility, we
      apply the method to a genetic association study of large for gestational age
      (LGA) neonates. The model provides a powerful tool for elucidating the genetic
      basis of complex binary diseases.

PMID- 19384428
TI  - Regulation of Nuclear Import During Differentiation; The IMP alpha Gene Family
      and Spermatogenesis.
AB  - Access to nuclear genes in eukaryotes is provided by members of the importin
      (IMP) superfamily of proteins, which are of alpha- or beta-types, the best
      understood nuclear import pathway being mediated by a heterodimer of an IMP alpha
      and IMP beta1. IMP alpha recognises specific targeting signals on cargo proteins,
      while IMP beta1 mediates passage into, and release within, the nucleus by
      interacting with other components of the transport machinery, including the
      monomeric guanine nucleotide binding protein Ran. In this manner, hundreds of
      different proteins can be targeted specifically into the nucleus in a tightly
      regulated fashion. The IMP alpha gene family has expanded during evolution, with
      only a single IMP alpha (Srp1p) gene in budding yeast, and three (IMP alpha1,
      2/pendulin and 3) and five (IMP alpha1, -2, -3, -4 and -6) IMP alpha genes in
      Drosophila melanogaster and mouse respectively, which fall into three
      phylogenetically distinct groups. The fact that IMP alpha3 and IMP alpha2 are
      only present in metazoans implies that they emerged during the evolution of
      multicellular animals to perform specialised roles in particular cells and
      tissues. This review describes what is known of the IMP alpha gene family in
      mouse and in D. melanogaster, including a comparitive examination of their mRNA
      expression profiles in a highly differentiated tissue, the testis. The clear
      implication of their highly regulated synthesis during the course of
      spermatogenesis is that the different IMP alphas have distinct expression
      patterns during cellular differentiation, implying tissue/cell type-specific
      roles.

PMID- 19384429
TI  - Ovarian cancer biomarkers: a focus on genomic and proteomic findings.
AB  - Among the gynaecological malignancies, ovarian cancer is one of the neoplastic
      forms with the poorest prognosis and with the bad overall and disease-free
      survival rates than other gynaecological cancers; several studies, analyzing
      clinical data and pathological features on ovarian cancers, have focused on the
      identification of both diagnostic and prognostic markers for applications in
      clinical practice. High-throughput technologies have accelerated the process of
      biomarker discovery, but their validity should be still demonstrated by extensive
      researches on sensibility and sensitivity of ovarian cancer novel biomarkers,
      determining whether gene profiling and proteomics could help differentiate
      between patients with metastatic ovarian cancer and primary ovarian carcinomas,
      and their potential impact on management.Therefore, considerable interest lies in
      identifying molecular prognostic biomarkers and protein indicators to guide
      treatment decisions and clinical follow up; the current state of knowledge about
      the potential clinical value of gene expression profiling in ovarian cancer is
      discussed, focusing on three main areas: distinguishing normal ovarian tissue
      from ovarian tumors, identifying different subtypes of ovarian cancer and
      identifying cancer likely to be responsive to therapy.In this elaborate we
      discuss the use of novel molecules, discovered by proteomics and genomics
      approaches, as potential protein biomarkers in the management of ovarian cancer,
      to improve the anticancer therapy for malignant ovarian tumors and to monitor the
      clinical follow up.

PMID- 19384431
TI  - The pervasive chemistry of metal-organic frameworks.

PMID- 19384430
TI  - A general quantitative genetic model for haplotyping a complex trait in humans.
AB  - Uncertainty about linkage phases of multiple single nucleotide polymorphisms
      (SNPs) in heterozygous diploids challenges the identification of specific DNA
      sequence variants that encode a complex trait. A statistical technique
      implemented with the EM algorithm has been developed to infer the effects of SNP
      haplotypes from genotypic data by assuming that one haplotype (called the risk
      haplotype) performs differently from the rest (called the non-risk haplotype).
      This assumption simplifies the definition and estimation of genotypic values of
      diplotypes for a complex trait, but will reduce the power to detect the risk
      haplotype when non-risk haplotypes contain substantial diversity. In this
      article, we incorporate general quantitative genetic theory to specify the
      differentiation of different haplotypes in terms of their genetic control of a
      complex trait. A model selection procedure is deployed to test the best number
      and combination of risk haplotypes, thus providing a precise and powerful test of
      genetic determination in association studies. Our method is derived on the
      maximum likelihood theory and has been shown through simulation studies to be
      powerful for the characterization of the genetic architecture of complex
      quantitative traits.

PMID- 19384432
TI  - Design of MOFs and intellectual content in reticular chemistry: a personal view.
AB  - This article gives a personal perspective on the ideas leading to the development
      of reticular chemistry. The feasibility of achieving targeted materials with
      predetermined metrics and functionality by designed synthesis is defended.

PMID- 19384433
TI  - Infinite coordination polymer nano- and microparticle structures.
AB  - Infinite coordination polymer particles (ICPs) represent an area of growing
      interest in chemistry and materials science due to their unique and highly
      tailorable properties. These structures can be conveniently synthesized in high
      yields from the appropriate metal salts and bifunctional ligand precursors.
      Unlike conventional metal-organic framework materials (MOFs), these ICPs exhibit
      a higher level of structural tailorability, including size- and morphology
      dependent properties, and therefore, the promise of a wider scope of utility. A
      variety of methods now exist for making numerous compositions, with modest
      control over particle size and shape. These structures can exhibit microporosity,
      tunable fluorescence, magnetic susceptibility, and unusual catalytic activity and
      selectivity. Perhaps most importantly, many of these ICP structures can be
      depolymerized (sometimes reversibly) much faster and under milder conditions than
      MOFs, which makes them attractive for a variety of biomedical applications. Thus
      far, several types of ICPs have been explored as contrast agents for magnetic
      resonance imaging and drug delivery systems. The groundwork for this emerging
      field of ICPs has been laid only in the past few years, yet significant advances
      have already been made. Indeed, this tutorial review introduces the reader to the
      field of ICPs, providing a guide to the work done so far, with an emphasis on
      synthesis, applications and future prospects.

PMID- 19384434
TI  - Polymerization reactions in porous coordination polymers.
AB  - Recent developments in polymerizations within the nanochannels of porous
      coordination polymers (PCPs) are covered in this tutorial review. The
      characteristic features of PCPs are regular structures, controllable channel
      sizes and shapes, a designable surface functionality, and flexible frameworks,
      which can be utilized for precision polymer synthesis and specific polymer
      confinement. This review discusses promising approaches to multiple controls of
      polymer structures, analysis systems for low-dimensional polymer assemblies and
      the construction of PCP-polymer nanohybrids, which are strong enticements to
      researchers in the areas of inorganic, materials and polymer chemistry.

PMID- 19384435
TI  - Using molecular simulation to characterise metal-organic frameworks for
      adsorption applications.
AB  - Molecular simulation is a powerful tool to predict adsorption and to gain insight
      into the corresponding molecular level phenomena. In this tutorial review, we
      provide an overview of how molecular simulation can be used to characterise metal
      organic frameworks for adsorption applications. Particular attention is drawn to
      how these insights can be combined to develop design principles for specific
      applications.

PMID- 19384436
TI  - Enantioselective catalysis with homochiral metal-organic frameworks.
AB  - This tutorial review presents recent developments of homochiral metal-organic
      frameworks (MOFs) in enantioselective catalysis. Following a brief introduction
      of the basic concepts and potential virtues of MOFs in catalysis, we summarize
      three distinct strategies that have been utilized to synthesize homochiral MOFs.
      Framework stability and accessibility of the open channels to reagents are then
      addressed. We finally survey recent successful examples of catalytically active
      homochiral MOFs based on three approaches, namely, homochiral MOFs with achiral
      catalytic sites, incorporation of asymmetric catalysts directly into the
      framework, and post-synthetic modification of homochiral MOFs. Although still in
      their infancy, homochiral MOFs have clearly demonstrated their utility in
      heterogeneous asymmetric catalysis, and a bright future is foreseen for the
      development of practically useful homochiral MOFs in the production of optically
      pure organic molecules.

PMID- 19384426
TI  - The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and
      therapeutic implications.
AB  - The phosphoinositide 3-kinase (PI3K) pathway is frequently activated in human
      cancer and represents an attractive target for therapies based on small molecule
      inhibitors. PI3K isoforms play an essential role in the signal transduction
      events activated by cell surface receptors including receptor tyrosine kinases
      (RTKs) and G-protein-coupled receptors (GPCRs). There are eight known PI3K
      isoforms in humans, which have been subdivided into three classes (I-III).
      Therefore PI3Ks show considerable diversity and it remains unclear which kinases
      in this family should be targeted in cancer. The class I(A) of PI3K comprises the
      p110alpha, p110beta and p110delta isoforms, which associate with activated RTKs.
      In human cancer, recent reports have described activating mutations in the PIK3CA
      gene encoding p110alpha, and inactivating mutations in the phosphatase and tensin
      homologue (PTEN) gene, a tumour suppressor and antagonist of the PI3K pathway.
      The PIK3CA mutations described in cancer constitutively activate p110alpha and,
      when expressed in cells drive oncogenic transformation. Moreover, these mutations
      cause the constitutive activation of downstream signaling molecules such as
      Akt/protein kinase B (PKB), mammalian target of rapamycin (mTOR) and ribosomal
      protein S6 kinase (S6K) that is commonly observed in cancer cells. In addition to
      p110alpha, the other isoforms of the PI3K family may also play a role in human
      cancer, although their individual functions remain to be precisely identified. In
      this review we will discuss the evidence implicating individual PI3K isoforms in
      human cancer and their potential as drug targets in this context.

PMID- 19384437
TI  - Secondary building units, nets and bonding in the chemistry of metal-organic
      frameworks.
AB  - This critical review presents a comprehensive study of transition-metal
      carboxylate clusters which may serve as secondary building units (SBUs) towards
      construction and synthesis of metal-organic frameworks (MOFs). We describe the
      geometries of 131 SBUs, their connectivity and composition. This contribution
      presents a comprehensive list of the wide variety of transition-metal carboxylate
      clusters which may serve as secondary building units (SBUs) in the construction
      and synthesis of metal-organic frameworks. The SBUs discussed here were obtained
      from a search of molecules and extended structures archived in the Cambridge
      Structure Database (CSD, version 5.28, January 2007) which included only crystals
      containing metal carboxylate linkages (241 references).

PMID- 19384438
TI  - Industrial applications of metal-organic frameworks.
AB  - New materials are prerequisite for major breakthrough applications influencing
      our daily life, and therefore are pivotal for the chemical industry. Metal
      organic frameworks (MOFs) constitute an emerging class of materials useful in gas
      storage, gas purification and separation applications as well as heterogeneous
      catalysis. They not only offer higher surface areas and the potential for
      enhanced activity than currently used materials like base metal oxides, but also
      provide shape/size selectivity which is important both for separations and
      catalysis. In this critical review an overview of the potential applications of
      MOFs in the chemical industry is presented. Furthermore, the synthesis and
      characterization of the materials are briefly discussed from the industrial
      perspective (88 references).

PMID- 19384439
TI  - Hydrogen storage in metal-organic frameworks.
AB  - New materials capable of storing hydrogen at high gravimetric and volumetric
      densities are required if hydrogen is to be widely employed as a clean
      alternative to hydrocarbon fuels in cars and other mobile applications. With
      exceptionally high surface areas and chemically-tunable structures, microporous
      metal-organic frameworks have recently emerged as some of the most promising
      candidate materials. In this critical review we provide an overview of the
      current status of hydrogen storage within such compounds. Particular emphasis is
      given to the relationships between structural features and the enthalpy of
      hydrogen adsorption, spectroscopic methods for probing framework-H(2)
      interactions, and strategies for improving storage capacity (188 references).

PMID- 19384440
TI  - Postsynthetic modification of metal-organic frameworks.
AB  - The modification of metal-organic frameworks (MOFs) in a postsynthetic scheme is
      discussed in this critical review. In this approach, the MOF is assembled and
      then modified with chemical reagents with preservation of the lattice structure.
      Recent findings show amide couplings, isocyanate condensations, 'click'
      chemistry, and other reactions are suitable for postsynthetic modification (PSM).
      In addition, a number of MOFs, from IRMOF-3 to ZIF-90, are amenable to PSM. The
      generality of PSM, in both scope of chemical reactions and range of suitable
      MOFs, clearly indicates that the approach is broadly applicable. Indeed, the
      rapid increase in reports on PSM demonstrates this methodology will play an
      increasingly important role in the development of MOFs for the foreseeable future
      (117 references).

PMID- 19384441
TI  - Luminescent metal-organic frameworks.
AB  - Metal-organic frameworks (MOFs) display a wide range of luminescent behaviors
      resulting from the multifaceted nature of their structure. In this critical
      review we discuss the origins of MOF luminosity, which include the linker, the
      coordinated metal ions, antenna effects, excimer and exciplex formation, and
      guest molecules. The literature describing these effects is comprehensively
      surveyed, including a categorization of each report according to the type of
      luminescence observed. Finally, we discuss potential applications of luminescent
      MOFs. This review will be of interest to researchers and synthetic chemists
      attempting to design luminescent MOFs, and those engaged in the extension of MOFs
      to applications such as chemical, biological, and radiation detection, medical
      imaging, and electro-optical devices (141 references).

PMID- 19384442
TI  - Magnetic metal-organic frameworks.
AB  - The purpose of this critical review is to give a representative and comprehensive
      overview of the arising developments in the field of magnetic metal-organic
      frameworks, in particular those containing cobalt(II). We examine the diversity
      of magnetic exchange interactions between nearest-neighbour moment carriers,
      covering from dimers to oligomers and discuss their implications in infinite
      chains, layers and networks, having a variety of topologies. We progress to the
      different forms of short-range magnetic ordering, giving rise to single-molecule
      magnets and single-chain-magnets, to long-range ordering of two- and three
      dimensional networks (323 references).

PMID- 19384443
TI  - Large breathing effects in three-dimensional porous hybrid matter: facts,
      analyses, rules and consequences.
AB  - This critical review focuses on a strange behaviour of crystallized solid matter:
      its reversible swelling with large magnitude. This will be of interest for
      experts in porous solids but also for solid state chemists and physicists. Some
      examples, classified according to the dimensionality of the inorganic subnetwork,
      present the general requirements and the structural rules which govern the
      existence of this phenomenon. Its consequences concern specific applications
      related to sensors, energy savings, sustainable development and health (100
      references).

PMID- 19384444
TI  - Design and synthesis of metal-organic frameworks using metal-organic polyhedra as
      supermolecular building blocks.
AB  - This critical review highlights supermolecular building blocks (SBBs) in the
      context of their impact upon the design, synthesis, and structure of metal
      organic materials (MOMs). MOMs, also known as coordination polymers, hybrid
      inorganic-organic materials, and metal-organic frameworks, represent an emerging
      class of materials that have attracted the imagination of solid-state chemists
      because MOMs combine unprecedented levels of porosity with a range of other
      functional properties that occur through the metal moiety and/or the organic
      ligand. First generation MOMs exploited the geometry of metal ions or secondary
      building units (SBUs), small metal clusters that mimic polygons, for the
      generation of MOMs. In this critical review we examine the recent (<5 years)
      adoption of much larger scale metal-organic polyhedra (MOPs) as SBBs for the
      construction of MOMs by highlighting how the large size and high symmetry of such
      SBBs can afford improved control over the topology of the resulting MOM and a new
      level of scale to the resulting framework (204 references).

PMID- 19384445
TI  - Thin films of metal-organic frameworks.
AB  - The fabrication of thin film coatings of metal-organic frameworks (MOFs) on
      various substrates is discussed in this critical review. Interestingly, the
      relatively few studies on MOF films that have appeared in the literature are
      limited to the following cases: [Zn4O(bdc)3] (MOF-5; bdc=1,4
      benzenedicarboxylate), [Cu3(btc)2] (HKUST-1; btc=1,3,5-benzenetricarboxylate),
      [Zn2(bdc)2(dabco)] (dabco=1,4-diazabicyclo[2.2.2]octane), [Mn(HCOO)],
      [Cu2(pzdc)2(pyz)] (CPL-1; pzdc=pyrazine-2,3-dicarboxylate, pyz=pyrazine),
      [Fe(OH)(bdc)] (MIL-53(Fe)) and [Fe3O(bdc)3(Ac)] (MIL-88B; Ac=CH3COO-). Various
      substrates and support materials have been used, including silica, porous
      alumina, graphite and organic surfaces, i.e. self-assembled monolayers (SAMs) on
      gold, as well as silica surfaces. Most of the MOF films were grown by immersion
      of the selected substrates into specifically pre-treated solvothermal mother
      liquors of the particular MOF material. This results in more or less densely
      packed films of intergrown primary crystallites of sizes ranging up to several
      microm, leading to corresponding film thicknesses. Alternatively, almost
      atomically flat and very homogenous films, with thicknesses of up to ca. 100 nm,
      were grown in a novel stepwise layer-by-layer method. The individual growth steps
      are separated by removing unreacted components via rinsing the substrate with the
      solvent. The layer-by-layer method offers the possibility to study the kinetics
      of film formation in more detail using surface plasmon resonance. In some cases,
      particularly on SAM-modified substrates, a highly oriented growth was observed,
      and in the case of the MIL-53/MIL-88B system, a phase selective deposition of MIL
      88B, rather than MIL-53(Fe), was reported. The growth of MOF thin films is
      important for smart membranes, catalytic coatings, chemical sensors and related
      nanodevices (63 references).

PMID- 19384446
TI  - Phosphonate and sulfonate metal organic frameworks.
AB  - Recent progress in phosphonate and sulfonate MOFs is reviewed with an emphasis on
      open frameworks. These two ligating functionalities are paired due to their
      structural analogy but the review will show that their differences likely
      outweigh their similarities when it comes to their framework structures and
      properties. Examples that are highlighted focus on new routes to open structures,
      demonstrations of porosity and functionality, and examples with dynamic
      structures. This critical review is geared to researchers interested in designing
      open framework solids (134 references).

PMID- 19384447
TI  - Metal-organic framework materials as catalysts.
AB  - A critical review of the emerging field of MOF-based catalysis is presented.
      Discussed are examples of: (a) opportunistic catalysis with metal nodes, (b)
      designed catalysis with framework nodes, (c) catalysis by homogeneous catalysts
      incorporated as framework struts, (d) catalysis by MOF-encapsulated molecular
      species, (e) catalysis by metal-free organic struts or cavity modifiers, and (f)
      catalysis by MOF-encapsulated clusters (66 references).

PMID- 19384448
TI  - Recent advances on simulation and theory of hydrogen storage in metal-organic
      frameworks and covalent organic frameworks.
AB  - This critical review covers the application of computer simulations, including
      quantum calculations (ab initio and DFT), grand canonical Monte-Carlo
      simulations, and molecular dynamics simulations, to the burgeoning area of the
      hydrogen storage by metal-organic frameworks and covalent-organic frameworks.
      This review begins with an overview of the theoretical methods obtained from
      previous studies. Then strategies for the improvement of hydrogen storage in the
      porous materials are discussed in detail. The strategies include appropriate pore
      size, impregnation, catenation, open metal sites in metal oxide parts and within
      organic linker parts, doping of alkali elements onto organic linkers,
      substitution of metal oxide with lighter metals, functionalized organic linkers,
      and hydrogen spillover (186 references).

PMID- 19384449
TI  - Selective gas adsorption and separation in metal-organic frameworks.
AB  - Adsorptive separation is very important in industry. Generally, the process uses
      porous solid materials such as zeolites, activated carbons, or silica gels as
      adsorbents. With an ever increasing need for a more efficient, energy-saving, and
      environmentally benign procedure for gas separation, adsorbents with tailored
      structures and tunable surface properties must be found. Metal-organic frameworks
      (MOFs), constructed by metal-containing nodes connected by organic bridges, are
      such a new type of porous materials. They are promising candidates as adsorbents
      for gas separations due to their large surface areas, adjustable pore sizes and
      controllable properties, as well as acceptable thermal stability. This critical
      review starts with a brief introduction to gas separation and purification based
      on selective adsorption, followed by a review of gas selective adsorption in
      rigid and flexible MOFs. Based on possible mechanisms, selective adsorptions
      observed in MOFs are classified, and primary relationships between adsorption
      properties and framework features are analyzed. As a specific example of tailor
      made MOFs, mesh-adjustable molecular sieves are emphasized and the underlying
      working mechanism elucidated. In addition to the experimental aspect, theoretical
      investigations from adsorption equilibrium to diffusion dynamics via molecular
      simulations are also briefly reviewed. Furthermore, gas separations in MOFs,
      including the molecular sieving effect, kinetic separation, the quantum sieving
      effect for H2/D2 separation, and MOF-based membranes are also summarized (227
      references).

PMID- 19384450
TI  - Kinetic analysis of experimental rabbit tumour and inflammation model with 18F
      FDG PET/CT.
AB  - Non-specific accumulation of 18F-FDG by both tumour and inflammatory lesions can
      make diagnostic analysis difficult. Our aim was to explore the difference in 18F
      FDG uptake kinetics between tumour and inflammatory cells. To this end, we
      investigated VX2 tumour lesions and inflammatory lesions in rabbits. METHODS: Six
      rabbits with VX2 tumour cells transplanted into one forelimb muscle and
      inflammatory lesions induced by turpentine oil in the contralateral forelimb were
      scanned for 60 minutes post 18F-FDG injection. Imaging data was analyzed with the
      standard 2-tissue-compartment model. Parameters, VB, Ki, K1, k2, k3, k4, were
      compared between tumour and inflammatory lesions. SUV and dual time scan methods
      were also compared in the experiment. RESULTS: Time activity curves of VX2 tumour
      lesions showed a characteristic pattern of gradually increasing 18F-FDG uptake up
      to 60 min, whereas, 18F-FDG uptake in inflammatory lesions increased more slowly
      than in tumours. Parameters estimated from the uptake process showed that forward
      transport constant, K1, and influx constant, Ki, values in VX2 tumour lesions
      (0.186 +/- 0.053 and 0.048 +/- 0.014, respectively) was significantly higher than
      that in inflammatory lesions (0.129 +/- 0.024 and 0.022 +/- 0.007, respectively)
      (p < 0.05). In contrast, mean values of VB, k2, k3 and k4 derived from VX2
      tumours were not significantly different from that of inflammatory lesions. SUVs
      at 60 minutes post 18F-FDG injection were also significantly higher in the VX2
      tumor lesions than in the inflammatory lesions. Retention index (RI) was not
      significantly different between VX2 tumours and inflammatory lesions (1.134 +/-
      0.076 vs. 1.060 +/- 0.058, p > 0.05). CONCLUSION: Different kinetic parameters
      (Ki, K1, k3) exist between inflammatory and tumour lesions.

PMID- 19384451
TI  - The success of 131I ablation in thyroid cancer patients is significantly reduced
      after a diagnostic activity of 40 MBq 131I.
AB  - OBJECTIVE: Dosimetry studies have shown that activities of 131I as small as 10-20
      MBq may cause a stunning effect. A result of this stunning effect may be a lower
      success rate of the ablative 131I therapy for differentiated thyroid carcinoma
      (DTC). The aim of this study was to determine whether pre-therapeutic uptake
      measurement with 40 MBq 131I causes a lower success rate of ablation. DESIGN:
      retrospective chart review study. PATIENTS, METHODS: In two hospitals the
      ablation protocols differed in one respect only: in the one hospital no
      diagnostic 131I was applied before ablation (group 1, n = 48), whereas in the
      other hospital a 24-h uptake-measurement with 40 MBq 131I was performed (group 2,
      n = 51). Included were all DTC patients without distant metastases who had
      undergone 131I ablation between July 2002 and December 2005, and who had returned
      for 131I follow-up. Successful ablation was defined as absence of pathological
      131I uptake on diagnostic whole-body scintigraphy and undetectable thyroglobulin
      levels under TSH stimulation. RESULTS: Overall, ablation was successful in 31/48
      patients (65%) in group 1 and in 17/51 patients (33%) in group 2 (p=0.002).
      Multivariate analysis showed that pre-therapeutic uptake measurement using 40 MBq
      131I was an independent determinant for success of ablation (p = 0.002).
      CONCLUSIONS: After applying a diagnostic activity of 40 MBq 131I before ablation,
      the success rate of ablation is severely reduced. Consequently, the routine
      application of 131I for diagnostic scintigraphy or uptake measurement prior to
      131I ablation is best avoided.

PMID- 19384452
TI  - [Myocardial perfusion scintigraphy 2007 in Germany--results of the query and
      current status].
AB  - AIM: This third survey of the working group Cardiovascular Nuclear Medicine of
      the German Society of Nuclear Medicine in cooperation with the working group
      Nuclear Cardiology of the German Cardiac Society was to deliver information on
      the procedures and in particular on the development of myocardial perfusion
      scintigraphy (MPS) from 2005 to 2007. METHOD: 370 questionnaires (222 private
      practices (PP), 117 hospitals (HO), 31 university hospitals (UH)) were evaluated.
      RESULTS: MPS of 114,374 patients were reported, 83% were investigated with 99mTc
      perfusion tracers. 76% [2006=74%] were performed in PP, 15% [2006=17%] in HO and
      9% [2006=9%] in UH. Diabetics represented 21% of all MPS patients in 2007. Data
      of 215 institutions which participated all from 2005 to 2007 showed an increase
      in MPS of 2.3% (PP +6.8%, HO -4.5%, UH -18.2%). The type of stress was
      pharmacological in 27% [2006 = 27%]; 67% adenosine (of these 25% with exercise),
      31% dipyridamole (of these 55% with exercise), and 2% dobutamine. Gated SPECT was
      performed in 47% [2006 = 42%] of all rest and in 44% [2006 = 39%] of all stress
      MPS. 61% [2006 = 83%] of all institutions did not apply perfusion scores. 20%
      [2006 = 24%] of the institutions reported changes in the use of MPS by competing
      methods. CONCLUSION: There is a small increase of MPS between 2005 and 2007
      despite competing methods. Gated SPECT has experienced more acceptance, but is
      still underrepresented. As compared to the European average and general standards
      of MPS a considerable backlog accounts to pharmacological stress tests, gated
      SPECT and perfusion scores.

PMID- 19384453
TI  - [Regional anaesthesia as advantage in competition between hospitals. Strategic
      market analysis].
AB  - BACKGROUND: The German Social Act V section sign 12 is aimed towards competition,
      efficiency and quality in healthcare. Because surgical departments are billing
      standard diagnosis-related group (DRG) case costs to health insurance companies,
      they claim best value for money for internal services. Thus, anaesthesia concepts
      are being closely scrutinized. The present analysis was performed to gain
      economic arguments for the strategic positioning of regional anaesthesia
      procedures into clinical pathways. METHODS: Surgical procedures, which in 2005
      had a relevant caseload in Germany, were chosen in which regional anaesthesia
      procedures (alone or in combination with general anaesthesia) could routinely be
      used. The structure of costs and earnings for hospital services, split by types
      and centres of cost, as well as by underlying procedures are contained in the
      annually updated public accessible dataset (DRG browser) of the German Hospital
      Reimbursement Institute (InEK). For the year 2005 besides own data, national
      anaesthesia staffing costs are available from the German Society of
      Anaesthesiology (DGAI). The curve of earnings per DRG can be calculated from the
      2005 InEK browser. This curve intersects by the cost curve at the point of
      national mean length of stay. The cost curve was calculated by process-oriented
      distribution of cost centres over the length of stay and allows benchmarking
      within the national competitive environment. For comparison of process times data
      from our local database were used. While the InEK browser lacks process times,
      the cost positions 5.1-5.3 (staffing costs anaesthesia) and the national
      structure adjusted anaesthesia staffing costs 2005 as published by the DGAI, were
      used to calculate nationwide mean available anaesthesia times which were compared
      with own process times. RESULTS: Within the portfolio diagram of lengths of stay
      for each DRG and process times most procedures are located in the economic lower
      left, in particular those with high case mix (length of stay and anaesthesia
      times below reimbursement relevant national mean). The driver of increased
      earnings is shortening length of stay. Our use of regional anaesthesia is 5 to 10
      fold higher than national benchmarks and may contribute to our advantageous
      position in national competition. The annual increases in profit per DRG range
      between EUR 1,706 and EUR 467,359 and compensate by far the investment of
      regional anaesthesia derived pain management, besides the advantage of increased
      patient satisfaction and avoidance of complications. CONCLUSION: Regional
      anaesthesia is a considerable value driver in clinical pathways by shortening
      length of stay. The present analysis further demonstrates that time for regional
      block performance is covered by anaesthesia reimbursement within the DRG costing
      schedule.

PMID- 19384454
TI  - [Burn trauma--Part 2. Anesthesiological, surgical and intensive care management].
AB  - After initial stabilization of burn victims at the scene and in the trauma room,
      a tight cooperation and communication between anesthesiologists, plastic surgeons
      and intensive care specialists is needed for further therapy. Interdisciplinary
      communication about preoperative planning, timing of necrectomy and intensive
      care therapy is vital regarding functional and aesthetic outcome and survival
      rate. During burn surgery attention has to be paid to excessive blood loss and
      the danger of hypothermia. The main problems of intensive care therapy involve
      the evaluation of volume status, high demands for analgesia and sedation, high
      incidence of septic multiorgan failure and therapy and prophylaxis of the effects
      of hypermetabolism.

PMID- 19384455
TI  - [Problematic of intra-abdominal pressure measurement].
AB  - Intra-abdominal hypertension (intra-abdominal pressure, IAP>12 mmHg) is observed
      in more than 30% of critically ill patients and is of major prognostic relevance.
      Unfortunately, clinical examination alone does not allow the IAP to be estimated
      with sufficient accuracy. Consequently, IAP monitoring should be considered if
      risk factors for intra-abdominal hypertension are present in order to enable
      early therapeutic intervention. A technically simple estimation of IAP is
      possible by intravesical pressure measurements. Alternatively, intragastric
      pressure can be measured continuously and IAP changes can be detected rapidly. In
      addition the development of IAP values over time can be appreciated more
      comprehensively compared to single snapshot-like measurements. The goal of IAP
      monitoring is not to keep the IAP below a certain threshold, but rather to
      establish a sufficient abdominal perfusion pressure [APP=mean arterial pressure
      (MAP)-IAP] of 50-60 mmHg. However, no data have yet been provided showing that
      the routine use of IAP monitoring and APP targeted therapy is able to improve the
      prognosis of critically ill patients.

PMID- 19384456
TI  - [Cardiac preload and central venous pressure].
AB  - The force of cardiac contraction is strongly influenced by myocardial fibre
      length at the beginning of systole. Because the length of cardiac sarcomers and
      muscle fibres primarily depends on the end-diastolic ventricular volume, filling
      pressures a priori can only act as indirect parameters of cardiac preload.
      Central venous pressure (CVP) gives information on right ventricular end
      diastolic pressure, which parallels changes in left ventricular end-diastolic
      pressure as long as ventricular function is not impaired. Since the pressure
      volume relationship of cardiac ventricles is not linear and shows great
      variability, filling of the ventricles cannot be directly derived from end
      diastolic pressure. Further limitations of CVP as a surrogate variable of preload
      are caused by the influence of intrathoracic and intra-abdominal pressures. A
      valid parameter of preload should describe the relationship between preload and
      stroke volume as given by the Frank-Starling law. Furthermore, estimates of
      cardiac preload should enable prediction of fluid responsiveness. Many studies
      have demonstrated that under clinical conditions CVP cannot meet these demands
      and thus does not appear to be a useful predictor of cardiac preload. Variables
      which more directly represent end-diastolic ventricular volume (e.g.
      intrathoracic blood volume or end-diastolic ventricular area) offer a higher
      validity as estimates of cardiac preload. Furthermore, dynamic parameters of
      ventricular preload, such as pulse pressure variation or stroke volume variation,
      seem to be more predictive of volume responsiveness in ventilated patients than
      CVP. These limitations, however, do not impair the importance of CVP as the
      downstream pressure of the systemic venous system.

PMID- 19384457
TI  - [Airway management in a patient with immobilized cervical spine. Preclinical use
      of the McGrath video-laryngoscope].
AB  - The McGrath video-laryngoscope was used in a patient with immobilized cervical
      spine and suspected difficult airway after a high level fall with traumatic brain
      injury and suspected cervical spine trauma. The airway was successfully secured
      in the preclinical setting using an oral endotracheal tube with full view of the
      glottis. Because video-laryngoscopy offers potential advantages compared to
      established airway management techniques, further studies are required to
      evaluate the significance of video-laryngoscopy in prehospital emergency
      medicine.

PMID- 19384458
TI  - Evaluation of POSSUM for patients undergoing pancreatoduodenectomy.
AB  - BACKGROUND: Comparison of operative morbidity rates after pancreatoduodenectomy
      between units may be misleading because it does not take into account the
      physiological variable of the condition of the patients. The aim of the present
      study was to evaluate the Physiological and Operative Severity Score for the
      enUmeration of Mortality and Morbidity (POSSUM) for pancreatoduodenectomy
      patients and to look for risk factors associated with morbidity in a high-volume
      center. METHODS: Between January 1993 and April 2006, 652 patients underwent a
      pancreatoduodenectomy, 502 of them for malignant disease. POSSUM performance was
      evaluated by assessing the "goodness-of-fit" with the linear analysis method.
      RESULTS: Overall, 332 of the 652 patients (50.9%) had one or more complication
      after pancreatoduodenectomy, and 9 patients (1.4%) died. POSSUM had a significant
      lack of fit using goodness-of-fit analysis. In multivariate analysis, one
      statistically significant factor associated with morbidity and not incorporated
      in POSSUM (P < 0.05) was identified: ampulla of Vater adenocarcinoma (OR = 1.73,
      95% CI: 1.07-2.80). CONCLUSIONS: Overall, there is a lack of calibration of
      POSSUM among patients who undergo pancreatoduodenectomy.

PMID- 19384459
TI  - Overcoming distance: video-conferencing as a clinical and educational tool among
      surgeons.
AB  - BACKGROUND: Since the 1960s, there has been substantial development in the uses
      of video-conferencing (VC) among medical personnel, including surgeons who have
      adopted the technology. METHODS: A report on our own experience with VC was
      combined with a comprehensive PubMed search with the key words telepresence,
      video-conferencing, video-teleconferencing, telementoring and surgery, trauma,
      follow-up, education, and multidisciplinary teams. A search through two peer
      reviewed telemedicine journals -- Journal of Telemedicine and Telecare and
      Telemedicine and e-Health Journal -- and references of all included papers and
      identified additional reports was conducted. RESULTS: A total of 517 articles
      were identified with 51 relevant manuscripts, which included the key phrases. VC
      is widely used among surgeons for telementoring surgical procedures and in trauma
      and emergency medicine. Furthermore, VC is widely used by multidisciplinary teams
      and for the follow-up of patients after surgery. CONCLUSIONS: VC is a common
      clinical tool for surgeons and provides a great opportunity to alter surgical
      practice and to offer patients the best expertise in surgical treatment despite
      long distances, especially in rural areas.

PMID- 19384460
TI  - Long-term quality of life after hepatic resection: health is not simply the
      absence of disease.
AB  - BACKGROUND: Due to advances in operative methods and perioperative care,
      mortality and morbidity following major hepatic resection have decreased
      substantially, making long-term quality of life (QoL) an increasingly prominent
      issue. We evaluated whether postoperative diagnosis was associated with long-term
      QoL and health in patients requiring hepatic surgery for benign or malignant
      disease. METHODS: QoL was evaluated using the European Organization for Research
      and Treatment of Cancer Quality of Life Questionnaire Core-30 and the liver
      specific QLQ-LMC21 module. RESULTS: Between 2002 and 2006, 249 patients underwent
      hepatic surgery for malignant (76%) and benign (24%) conditions. One hundred
      thirty-five patients were available for QoL analysis after a mean of 26.5 months.
      There was no statistical difference in global QoL scores between patients with
      malignant and benign diseases (p = 0.367). Neither the extent of the resection (>
      or =2 segments vs. <2 segments; p = 0.975; OR = 0.988; 95% CI = 0.461-2.119) nor
      patient age had a significant influence on overall QoL (p = 0.092). CONCLUSIONS:
      These results indicate that long-term QoL for patients who underwent liver
      resection for malignant disease is quite good and that a poor clinical prognosis
      does not seem to correlate with a poor QoL.

PMID- 19384461
TI  - Palmar type of median artery as a source of superficial palmar arch: a cadaveric
      study with its clinical significance.
AB  - The superficial palmar arch (SPA) and its contributing arteries are highly
      variable. The palmar type of median artery (PMA) can be involved in the formation
      of the SPA by replacing the superficial palmar branch of the radial artery (RA)
      or the ulnar artery (UA). The present study was undertaken to investigate the
      presence of the PMA and its contribution in the formation of SPA in 42 cadavers
      (84 upper limbs) of Indian origin. When there was a PMA, its outer diameter was
      measured in the carpal tunnel. The PMA was found in 13 upper limbs (15.4%), and
      of these ten incidences (11.9%), the PMA took part in the formation of SPA, and
      in three instances (3.5%), the PMA did not make up part of the SPA. Out of the
      ten cases in which the PMA contributed to the formation of SPA, in six cases
      (7.1%), the PMA anastomosed with the UA; in three cases (3.5%), the PMA
      anastomosed with both the UA and the RA, and in one incidence (1.1%), the PMA
      joined the arteria radialis indicis (deep branch of the RA) to complete the SPA.
      The outer diameters of the median arteries varied between 0.8 and 2.6 mm with the
      mean value of 1.7 mm. The present study concludes that the median-ulnar type of
      SPA was the most common type of SPA when the PMA was encountered as a source of
      superficial arterial arcade of the hand, followed by the radial-median-ulnar
      type. The vascular patterns found in this study are important to hand surgeons.
      The present study of PMA origin, course, and its contribution to the SPA will add
      to the existing knowledge of the vascular anatomy of forearm and hand.

PMID- 19384462
TI  - Efflux protein expression in human retinal pigment epithelium cell lines.
AB  - PURPOSE: The objective of this study was to characterize efflux proteins (P
      glycoprotein (P-gp), multidrug resistance proteins (MRP1-6) and breast cancer
      resistance protein (BCRP)) of retinal pigment epithelium (RPE) cell lines.
      METHODS: Expression of efflux proteins in two secondary (ARPE-19, D407) and two
      primary (HRPEpiC and bovine) RPE cell lines was measured by quantitative RT-PCR
      and western blotting. Furthermore, activity of MRP1 and MRP5 of ARPE-19 cell line
      was assessed with calcein-AM and carboxydichlorofluorescein (CDCF) probes.
      RESULTS: Similar efflux protein profile was shared between ARPE-19 and primary
      RPE cells, whereas D407 cell line was notably different. D407 cells expressed
      MRP2 and BCRP, which were absent in other cell lines and furthermore higher MRP3
      transcript expression was found. MRP1, MRP4 and MRP5 were identified from all
      human RPE cell lines and MRP6 was not expressed in any cell lines. The pattern of
      efflux protein expression did not change when ARPE-19 cells were differentiated
      on filters. The calcein-AM and CDCF efflux tests provided evidence supporting
      MRP1 and MRP5 activity in ARPE-19 cells. CONCLUSIONS: MRP1, MRP4 and MRP5 are the
      main efflux transporters in RPE cell lines. There are differences in efflux
      protein expression between RPE cell lines.

PMID- 19384463
TI  - Cytotoxicity of paclitaxel incorporated in PLGA nanoparticles on hypoxic human
      tumor cells.
AB  - PURPOSE: The aim of this work was to prepare paclitaxel-loaded PLGA nanoparticles
      and determine cytotoxicity of released paclitaxel for two hypoxic human tumor
      cell lines: breast carcinoma (MCF-7) and carcinoma cervicis (HeLa). METHODS:
      Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel were
      prepared by o/w emulsification-solvent evaporation method. Physicochemical
      characteristics of nanoparticles were studied. Cellular uptake of nanoparticles
      was evaluated by transmission electronic microscopy and fluorescence microscopy.
      Flow cytometry quantified the number of cells held in G(2)/M phase. Cell
      viability was determined by the ability of single cell to form colonies.
      Biodistribution of nanoparticles in mice was evaluated by fluorescence
      microscopy. RESULTS: The nanoparticles were spherical with average diameter 318
      +/- 5.1 nm. The encapsulation efficiency was 88.52%. The drug release profile in
      vitro exhibited a biphasic pattern. Cellular uptake was observed. Co-culture of
      tumor cells with paclitaxel-loaded nanoparticles demonstrated that released
      paclitaxel retained its bioactivity to block cells in G(2)/M phase. Paclitaxel
      loaded nanoparticles exhibited cytotoxic effect on both hypoxic MCF-7 and HeLa
      cells and its cytotoxicity was more significant than that of free paclitaxel.
      Fluorescent nanoparticles were mainly distributed to liver and spleen of mice.
      CONCLUSIONS: Paclitaxel-loaded PLGA nanoparticles may be considered a promising
      drug delivery system to eradicate hypoxic tumor cells.

PMID- 19384464
TI  - Nanoparticle coated submicron emulsions: sustained in-vitro release and improved
      dermal delivery of all-trans-retinol.
AB  - PURPOSE: The aim of this research is to investigate the dermal delivery of all
      trans-retinol from nanoparticle-coated submicron oil-in-water emulsions as a
      function of the initial emulsifier type, the loading phase of nanoparticles, and
      the interfacial structure of nanoparticle layers. METHODS: The interfacial
      structure of emulsions was characterized using freeze-fracture-SEM. In-vitro
      release and skin penetration of all-trans-retinol were studied using Franz
      diffusion cells with cellulose acetate membrane, and excised porcine skin. The
      distribution profile was obtained by horizontal sectioning of the skin using
      microtome-cryostat and HPLC assay. RESULTS: The steady-state flux of all-trans
      retinol from silica-coated lecithin emulsions was decreased (up to 90%) and was
      highly dependent on the initial loading phase of nanoparticles; incorporation
      from the aqueous phase provided more pronounced sustained release. For oleylamine
      emulsions, sustained release effect was not affected by initial location of
      nanoparticles. The skin retention significantly (p < or = 0.05) increased and was
      higher for positive oleylamine-stabilised droplets. All-trans-retinol was mainly
      localized in the epidermis with deeper distribution to viable skin layers in the
      presence of nanoparticles, yet negligible permeation (approximately 1% of
      topically applied dose) through full-thickness skin. CONCLUSIONS: Sustained
      release and targeted dermal delivery of all-trans-retinol from oil-in-water
      emulsions by inclusion of silica nanoparticles is demonstrated.

PMID- 19384465
TI  - Effect of tape stripping and adjuvants on immune response after intradermal DNA
      electroporation.
AB  - PURPOSE: DNA vaccines require both efficient delivery methods and appropriate
      adjuvants. Based on their mechanisms of action, we hypothesised that some
      adjuvants could enhance vaccine immunogenicity or direct the response towards Th1
      profile after intradermal DNA electroporation. METHODS: After intradermal
      electroporation of plasmid DNA encoding luciferase, mice received hyaluronidase,
      imiquimod, monophosphoryl lipid A or were tape stripped in order to modulate the
      immune response against the encoded protein. We measured total immunoglobulin G,
      IgG1, IgG2a titres and the cytokines produced by splenocyte cultures to assess
      both humoral and cellular response. The effect of tape stripping on the response
      against intradermally delivered ovalbumin protein was also assessed. RESULTS:
      Neither hyaluronidase nor imiquimod improved the immune response against the
      encoded luciferase. Monophosphoryl lipid A did not modify the cytokines
      production but increased the anti-luciferase IgG2a titres. Tape stripping
      significantly increased anti-luciferase IgG2a and IFN-gamma responses. It also
      enhanced the humoral response after intradermal injection of the ovalbumin
      protein. CONCLUSIONS: Tape stripping is able to increase the Th1 immune response
      against both DNA and protein vaccines. Therefore, tape stripping appears to have
      interesting adjuvant effect on intradermal vaccination.

PMID- 19384466
TI  - Local and sustained vascular endothelial growth factor delivery for angiogenesis
      using an injectable system.
AB  - PURPOSE: We hypothesize that a microsphere/hydrogel combination system could be
      useful for the local and sustained delivery of recombinant human vascular
      endothelial growth factor (rhVEGF) to enhance angiogenesis in vivo. METHODS:
      Poly(D,L-lactide-co-glycolide) (PLGA) microspheres containing rhVEGF were loaded
      into alginate gels by ionic cross-linking. The rhVEGF release from the system was
      monitored and bioactivity was tested in vitro. The combination system was
      subcutaneously injected into mice using a syringe, and new blood vessel formation
      was evaluated. RESULTS: Sustained rhVEGF release from the combination system was
      observed for 3 weeks, and the released rhVEGF remained bioactive. Endothelial
      cell proliferation was significantly enhanced when cells were cultured with the
      rhVEGF-releasing combination system in vitro. When the combination system was
      implanted, the granulation tissue layer was thicker with more newly formed blood
      vessels than that with a single dose VEGF injection. CONCLUSION: The rhVEGF
      release was controlled by varying relative portions of microspheres and hydrogels
      in combination delivery systems, which efficiently promoted new blood vessel
      formation in vivo. This combination system could be a promising delivery vehicle
      for therapeutic angiogenesis.

PMID- 19384467
TI  - Cellular responses to cancer chemopreventive agent D,L-sulforaphane in human
      prostate cancer cells are initiated by mitochondrial reactive oxygen species.
AB  - PURPOSE: Present study was undertaken to elucidate the mechanism of cellular
      responses to D,L-sulforaphane (SFN), a highly promising cancer chemopreventive
      agent. METHODS: Mitochondrial DNA deficient Rho-0 variants of LNCaP and PC-3
      cells were generated by culture in the presence of ethidium bromide. Apoptosis
      was assessed by analysis of cytoplasmic histone-associated DNA fragmentation and
      activation of caspase-3. Immunoblotting was performed to determine the expression
      of apoptosis- and cell cycle-regulating proteins. Generation of reactive oxygen
      species (ROS), mitochondrial membrane potential (MMP), and cell cycle
      distribution were measured by flow cytometry. RESULTS: The Rho-0 variants of
      LNCaP and PC-3 cells were significantly more resistant to SFN-induced ROS
      generation, apoptotic DNA fragmentation, disruption of MMP, cytosolic release of
      cytochrome c, and G2/M phase cell cycle arrest compared with corresponding wild
      type cells. SFN-induced autophagy, which serves to protect against apoptotic cell
      death in PC-3 and LNCaP cells, was also partially but markedly suppressed in Rho
      0 variants compared with wild-type cells. SFN statistically significantly
      inhibited activities of mitochondrial respiratory chain enzymes in LNCaP and PC-3
      cells. CONCLUSION: These results indicate, for the first time, that mitochondria
      derived ROS serve to initiate diverse cellular responses to SFN exposure in human
      prostate cancer cells.

PMID- 19384468
TI  - Calcein release from polymeric vesicles in blood plasma and PVA hydrogel.
AB  - PURPOSE: The main goal of this study was to show the long-term stability of
      vesicles from poly(2-methyl oxazoline-block-polydimethylsiloxane-block poly(2
      methyl oxazoline) (PMOXA-PDMS-PMOXA) in PBS, blood plasma and the feasibility to
      use these vesicles for drug release from PVA hydrogels. METHODS: The vesicle
      formation properties and loading efficiency was evaluated using fluorescent dyes.
      The stability of the vesicles was evaluated in buffer at pH 7 at room temperature
      and in 50% blood plasma at 37 degrees C. The calcein loaded vesicles were
      dispersed in a UV crosslinked PVA hydrogel. The stability of the vesicles in the
      hydrogel was observed over one week, before the vesicles were ruptured with
      Triton X-100. RESULTS: The vesicles are very stable in buffer, blood plasma, and
      the PVA hydrogel. In plasma 50% of the calcein is released in 48 h in the
      presence of sodium azide. The vesicles can be evenly dispersed in PVA and are
      stable. The release can be triggered and the calcein diffuses afterwards quickly
      throughout the gel. CONCLUSION: Polymeric vesicles can be used as diffusion
      barrier in hydrogels for the controlled release of water soluble drugs.

PMID- 19384469
TI  - Inhibition requirements of the human apical sodium-dependent bile acid
      transporter (hASBT) using aminopiperidine conjugates of glutamyl-bile acids.
AB  - PURPOSE: Synthesize aminopiperidine conjugates of glutamyl-bile acids (glu-BAs)
      and develop a hASBT inhibition model using the conformationally sampled
      pharmacophore (CSP) approach. METHODS: glu-BAs aminopiperidine conjugates were
      synthesized. hASBT inhibition was measured as K(i). A CSP-SAR model was built
      using structural and physico-chemical descriptors and evaluated via cross
      validation. RESULTS: Twenty-nine aminopiperidine conjugates were synthesized. All
      inhibited hASBT, with K(i) ranging from 0.95 to 31.8 muM. Amidation of the
      piperidine nitrogen slightly decreased activity, while replacement by a carbon
      increased potency. Esterification of the glutamic acid linker had a minor impact,
      suggesting that a negative charge around C-24 is not required for binding. Three
      quantitative CSP-SAR models were developed. The best model (r (2) = 0.813, Q (2)
      = 0.726) included two descriptors: angle between 7-OH, alpha-substituent and
      centroid of rings B and C, and electrostatic contribution to the solvation free
      energy. The model successfully distinguished between compounds with K(i) < 16muM
      and K(i) > 16muM. Models indicated that hydrophobicity, alpha substituent
      orientation, and partially compacted side chain conformation promote inhibitory
      potency. Qualitative CSP-SAR analysis indicated that the presence of an internal
      salt bridge, resulting in a locked conformation of the side chain, yielded weaker
      inhibitors. CONCLUSIONS: Aminopiperidine conjugates of glu-BAs were potent hASBT
      inhibitors. A predictive and robust CSP-SAR model was developed.

PMID- 19384470
TI  - Assessment of blood-brain barrier permeability using the in situ mouse brain
      perfusion technique.
AB  - PURPOSE: To assess the blood-brain barrier (BBB) permeability of 12 clinically
      used drugs in mdr1a(+/+) and mdr1a(-/-) mice, and investigate the influence of
      lipophilicity, nonspecific brain tissue binding, and P-gp-mediated efflux on the
      rate of brain uptake. METHODS: The BBB partition coefficient (PS) was determined
      using the in situ mouse brain perfusion technique. The net brain uptake for 12
      compounds, and the time course of brain uptake for selected compounds ranging in
      BBB equilibration kinetics from rapidly-equilibrating (e.g., alfentanil,
      sufentanil) to slowly-equilibrating (fexofenadine), was determined and compared.
      RESULTS: There was a sigmoidal relationship in mdr1a(-/-) mice between the log-PS
      and clogD(7.4) in the range of 0-5. The brain uptake clearance was a function of
      both permeability and blood flow rate. The brain unbound fraction was inversely
      proportional to lipophilicity. Alfentanil achieved brain equilibrium
      approximately 4,000-fold faster than fexofenadine, based on the magnitude of
      PSxfu,brain. CONCLUSIONS: In situ brain perfusion is a useful technique to
      determine BBB permeability. Lipophilicity, ionization state, molecular weight and
      polar surface area are all important determinants for brain penetration. The time
      to blood-to-brain equilibrium varies widely for different compounds, and is
      determined by a multiplicity of pharmacokinetic factors.

PMID- 19384471
TI  - PLGA and PHBV microsphere formulations and solid-state characterization: possible
      implications for local delivery of fusidic acid for the treatment and prevention
      of orthopaedic infections.
AB  - PURPOSE: To develop and characterize the solid-state properties of poly(DL-lactic
      co-glycolic acid) (PLGA) and poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid)
      (PHBV) microspheres for the localized and controlled release of fusidic acid
      (FA). METHODS: The effects of FA loading and polymer composition on the mean
      diameter, encapsulation efficiency and FA released from the microspheres were
      determined. The solid-state and phase separation properties of the microspheres
      were characterized using DSC, XRPD, Raman spectroscopy, SEM, laser confocal and
      real time recording of single microspheres formation. RESULTS: Above a loading of
      1% (w/w) FA phase separated from PLGA polymer and formed distinct spherical FA
      rich amorphous microdomains throughout the PLGA microsphere. For FA-loaded PLGA
      microspheres, encapsulation efficiency and cumulative release increased with
      initial drug loading. Similarly, cumulative release from FA-loaded PHBV
      microspheres was increased by FA loading. After the initial burst release, FA was
      released from PLGA microspheres much slower compared to PHBV microspheres.
      CONCLUSIONS: A unique phase separation phenomenon of FA in PLGA but not in PHBV
      polymers was observed, driven by coalescence of liquid microdroplets of a DCM-FA
      rich phase in the forming microsphere.

PMID- 19384472
TI  - Pericytes display increased CCN2 expression upon culturing.
AB  - By providing a source of alpha-smooth muscle actin (alpha-SMA)-expressing
      myofibroblasts, microvascular pericytes contribute to the matrix remodeling that
      occurs during tissue repair. However, the extent to which pericytes may
      contribute to the fibroblast phenotype post-repair is unknown. In this report, we
      test whether pericytes isolated from human placenta can in principle become
      fibroblast-like. Pericytes were cultured in vitro for 11 passages. The Affymetrix
      mRNA expression profile of passage 2 and passage 11 pericytes was compared. The
      expression of type I collagen, thrombospondin and fibronectin mRNAs was induced
      by passaging pericytes in culture. This induction of a fibroblast phenotype was
      paralleled by induction of connective tissue growth factor (CTGF/CCN2) and type I
      collagen protein expression and the fibroblast marker ASO2. These results
      indicate that, in principle, pericytes have the capacity to become fibroblast
      like and that pericytes may contribute to the population of fibroblasts in a
      healed wound.

PMID- 19384473
TI  - How to write an original article for the Journal of Orthopaedics and
      Traumatology.
AB  - The abstract is the precise summary of the article, not a preface. As Baue wrote
      in a popular editorial of the Archives of Surgery in 1979, "writing a good
      abstract is not abstract writing" [6]. The main data have to be represented, as
      they allow readers to understand contents clearly. Sentences like "The paper
      reports..." or "The authors describe..." have to be avoided as well as any
      generic statements.In order to help writers avoid generalities, the recently
      revised version of this journal's "instructions to authors" [4] requires the
      abstract to be no longer than 300 words and structured in 4 paragraphs: the
      Background declares the hypothesis, the Materials and methods impart the study
      design and quote the relevant numerical features of the samples, the Results
      report the main data and their statistical significance, the Conclusions state
      whether the hypothesis is verified or not. One or two sentences per paragraph are
      usually sufficient.The abstract is frequently recommended to be written after the
      text, as "the process of writing changes thought and perhaps even purpose" [7].
      Nonetheless, in my view, preparing the abstract first is a useful exercise that
      forces the authors to organize their thoughts and guides the organization of the
      article. However, the abstract should be always revised after the manuscript has
      been completed.

PMID- 19384474
TI  - Modular prostheses in the treatment of proximal humerus metastases: review of 40
      cases.
AB  - BACKGROUND: The humerus is the second most common site of metastatic bone disease
      involving long bones. Tumors which have a predilection for dissemination to bone
      are those of breast, prostate, thyroid, lung and kidney. The rationale for
      surgical treatment of these lesions is to prevent or treat pathological fractures
      in order to relieve pain and improve function. MATERIALS AND METHODS: Forty
      patients who had resection of the proximal humerus for metastatic bone disease
      and reconstruction with a modular prosthesis were retrospectively reviewed.
      RESULTS: Mean functional outcome was 73.1% (Enneking score) and better results
      were achieved when a reverse prosthesis was implanted. Overall survival was 70%
      at 1 year, 42.5% at 2 years and 20% at 5 years. Local recurrence occurred in 4
      patients, each of whom had initially been treated for a pathological fracture.
      CONCLUSIONS: It is important to follow rational guidelines, like those of Capanna
      and Mirels, in order to prevent pathological fractures and to give the patient a
      definitive treatment, as the advances in the management of cancer prolong the
      survival of these patients. In this series, satisfactory results were obtained,
      giving the patients an acceptable quality of life.

PMID- 19384475
TI  - Correction of knee and ankle valgus in hereditary multiple exostoses using the
      Ilizarov apparatus.
AB  - BACKGROUND: Hereditary multiple exostoses (HME) is a genetic disorder that causes
      limb deformities due to disturbance at the growth plates. MATERIALS AND METHODS:
      Six adolescents, whith symptomatic valgus deformity at the ankle and knee (seven
      affected legs) underwent correction procedures using the Ilizarov apparatus. In 5
      legs, a bifocal Ilizarov apparatus was used, whereas in 2 legs the use of a
      monofocal apparatus was sufficient. RESULTS: Correction of the mechanical axis
      was achieved in all cases, and limb length discrepancy was equalized in the 3
      cases that underwent limb elogation. The average knee and ankle corrections were
      15 degrees and 18 degrees , respectively. The average time from application to
      removal of the Ilizarove apparatus was 4.6 months. No major complication
      occurred. CONCLUSIONS: The use of the Ilizarov method in adolescents with HME
      enables successful simultaneous correction of multiplanar, multifocal complex
      limb deformities.

PMID- 19384476
TI  - How do porosity-inducing techniques affect antibiotic elution from bone cement?
      An in vitro comparison between hydrogen peroxide and a mechanical mixer.
AB  - BACKGROUND: Increasing the porosity of an antibiotic-loaded cement spacer
      increases the antibiotic elution, but the correlation between porosity and
      antibiotic elution is not well documented. The purposes of this study was to
      attempt new porosity-increasing methods and to investigate the correlation
      between antibiotic elution and both total and surface porosity. MATERIALS AND
      METHODS: Five types of antibiotic-loaded bone cement (ALBC) using 2 g cefazolin
      and 40 g cement were prepared. Other than manual mixing, hydrogen peroxide was
      used as a foaming agent and a mixing drill piece was used as a mechanical device
      to try to induce porosity when mixing the cement. Elution of antibiotic into
      phosphate-buffered saline was measured from 1 h to 1 week. Surface porosity was
      calculated from density values which were measured with a density kit and an
      electronic balance, while total porosity was quantified using micro-computed
      tomography. RESULTS: When a mixing drill piece was used to induce porosity, we
      observed a significant increasin antibiotic elution compared to a manually mixed
      ALBC. On the other hand, hydrogen peroxide reduced the elution significantly.
      Mild correlation between the total amount of cluted in 1 week antibiotic elution
      and total porosity was observed. CONCLUSIONS: In terms of improving elution, the
      mixing drill piece seemed to be efficient. A relationship between surface
      porosity and elution efficacy was not observed.

PMID- 19384477
TI  - Cost-effectiveness of cemented versus cementless total hip arthroplasty. A Markov
      decision analysis based on implant cost.
AB  - BACKGROUND: Probabilistic decision analysis is a means of reflecting the
      uncertainty parameter in models and of presenting it in a comprehensible manner
      to decision-makers. MATERIALS AND METHODS: A cost-effectiveness model was
      constructed to compare the cementless and cemented total hip prostheses implanted
      at our department in terms of lifetime costs and quality-adjusted life-years
      (QALY). Revision rates were obtained from the Orthopaedic Prosthesis Register of
      the Laboratory of Medical Technology, Istituti Ortopedici Rizzoli, Bologna,
      Italy. RESULTS: The risk of early revision (at 5 years of follow-up) for
      cementless and cemented prostheses was 1.6% and 1.4%, respectively, resulting in
      equal QALY for the two implant types. Analysis of mean cost and QALY indicated
      that use of either implant is not associated with cost savings. DISCUSSION:
      Management with cementless or cemented total hip prostheses in a theoretical
      cohort of 70-year-old patients with fracture of the femoral neck or arthritis
      involving the hip is not significantly different according to the probabilistic
      results from the model.

PMID- 19384478
TI  - Preventing acute infection in total hip prostheses implanted after external
      fixation of the femur: is there a need for a staged procedure?
AB  - We report two cases of acute infection of an uncemented femoral component in a
      hip prosthesis implanted after external fixation of a femoral fracture. In both
      cases, the surgical access did not cross over the pin scars. When the prosthesis
      was implanted the stem crossed one or more pin tracts. The preoperative clinical
      examination, laboratory tests and bone scintigraphy with marked granulocytosis
      did not show signs of local infection in either case. We suggest that every
      patient destined to receive a prosthesis after external fixation should be
      treated with a staged procedure, the first step being excision of the soft
      tissues around the pin tracts and curettage or drilling of the bony holes,
      followed by prosthesis implant.

PMID- 19384479
TI  - Elastofibroma dorsi: 8 case reports and a literature review.
AB  - A series of 8 cases of elastofibroma is reported, and the clinical, pathological
      and imaging features and different therapeutic modalities are reviewed. On this
      basis, we suggest an algorithm for the diagnosis and treatment of elastofibroma.
      Briefly, marginal excision is the treatment of choice in symptomatic patients,
      while followup appears to be a good solution in asymptomatic ones.

PMID- 19384480
TI  - Neglected patellar tendon rupture: a case of reconstruction without quadriceps
      lengthening.
AB  - Neglected rupture of the patellar tendon is a rare, can be easily missed in a
      group of patients. We present a 24 year old, male patient who sustained right
      femoral diaphyseal and tibial plateau fractures and a patellar tendon rupture
      following a motor vehicle accident. The fractures were treated by open reduction
      internal fixation but the patellar tendon rupture was missed and the diagnosis
      was delayed by 7 months. Patella was migrated proximally. It was moved distally
      to the original location and neglected patellar tendon rupture treated
      successfully with modified Ecker technique. Neither preoperative traction nor
      additional intraoperative procedures were performed to relocate the patella to
      its anatomic position in the extended knee and good functional result was
      achieved with intensive rehabilitation.

PMID- 19384481
TI  - The psoas muscle as cause of low back pain in infantile cerebral palsy.
AB  - Psoas muscle spasticity is hypothesised as a rare cause of low back pain in
      patients with infantile cerebral palsy. The authors describe a new manoeuvre for
      the study of psoas tenderness and ultrasound (US)-guided transabdominal botulinum
      toxin injection technique. A possible causal relationship between psoas tension
      and low back pain was found incidentally in two examined cases. In subsequent
      patients, botulinum toxin was injected and, in cases of disappearance of
      symptoms, the psoas tendon was sectioned at the pelvic brim with definitive
      disappearance of pain. The relationship between psoas tension and low back pain
      in patients with infantile cerebral palsy seems likely, given the result in the
      four patients.

PMID- 19384482
TI  - Perspectives on metaphyseal conservative stems.
AB  - Total hip replacement is showing, during the last decades, a progressive
      evolution toward principles of reduced bone and soft tissue aggression. These
      principles have become the basis of a new philosophy, tissue sparing surgery.
      Regarding hip implants, new conservative components have been proposed and
      developed as an alternative to conventional stems. Technical and biomechanical
      characteristics of metaphyseal bone-stock-preserving stems are analyzed on the
      basis of the available literature and our personal experience. Mayo, Nanos and
      Metha stems represent, under certain aspects, a design evolution starting from
      shared concepts: reduced femoral violation, non-anatomic geometry, proximal
      calcar loading and lateral alignment. However, consistent differences are level
      of neck preservation, cross-sectional geometry and surface finishing. The Mayo
      component is the most time-tested component and, in our hands, it showed an
      excellent survivorship at the mid-term follow-up, with an extremely reduced
      incidence of aseptic loosening (partially reduced by the association with last
      generation acetabular couplings). For 160 implants followed for a mean of 4.7
      years, survivorship was 97.5% with 4 failed implants: one fracture with unstable
      stem, 1 septic loosening and 2 aseptic mobilizations. DEXA analysis, performed on
      15 cases, showed a good calcar loading and stimulation, but there was significant
      lateral load transfer to R3-R4 zones, giving to the distal part of the stem a
      function not simply limited to alignment. Metaphyseal conservative stems
      demonstrated a wide applicability with an essential surgical technique. Moreover,
      they offer the options of a "conservative revision" with a conventional primary
      component in case of failure and a "conservative revision" for failed resurfacing
      implants.

PMID- 19384483
TI  - Arthroscopy surgery versus shock wave therapy for chronic calcifying tendinitis
      of the shoulder.
AB  - BACKGROUND: There are several treatment modalities for calcifying tendinitis of
      the shoulder. If the pain becomes chronic after several months of conservative
      treatment, open or arthroscopic removal is usually recommended. Recently,
      extracorporeal shock wave therapy has shown encouraging results in treating
      calcific deposits. MATERIALS AND METHODS: We report a retrospective study to
      compare the outcome after arthroscopic extirpation (group I, 22 cases) with the
      effect of low extracorporeal shock wave therapy (group II, 24 cases) in patients
      with a chronic homogeneous calcific deposit in the supraspinatus tendon. Patients
      included in the study had undergone unsuccessful conservative therapy in the
      previous six months with no evidence of subacromial impingement of the rotator
      cuff independent of the calcium deposit or rupture of the rotator cuff detected
      by sonography or magnetic resonance imaging. AP and LL radiographies were
      performed for all of the patients at least one week before the treatment and 24
      months after the treatment. To keep the possibility of spontaneous resorption
      low, the deposit had to be sharply outlined and densely structured on the
      radiograph (types I and II in the Gartner classification). In group II, the
      patients underwent an average of three treatment sessions of extracorporeal shock
      waves therapy with 1,500 impulses/session of 0.10-0.13 mJ/mm(2). RESULTS:
      Preoperative symptoms (P = 0.09), sex (P = 0.17), operated (P = 0.11) and
      dominant (P = 0.33) limbs, and age (P = 0.99) of the two groups did not show a
      significative difference between groups. According to the University of
      California Los Angeles (UCLA) rating system, the mean score in group I improved
      from 9.36 (+/-5.2) to 30.3 (+/-7.62) points after 24 months, with 81.81%
      reporting good or excellent results (P < 0.001). In group II the mean score after
      24 months rose from 12.38 (+/-6.5) to 28.13 (+/-9.34) points, with 70.83%
      reporting good or excellent results (P < 0.001). Radiologically, after two years
      of follow up, there was no calcific deposit in 86.35% (P < 0.001) of the patients
      of group I and in 58.33 % (P < 0.001) of the patients of group II. According to
      the UCLA scores, there was no significant difference between the groups at two
      years of follow-up (P = 0.38). CONCLUSIONS: We conclude that shock wave therapy
      is equivalent to arthroscopy, and so shock wave therapy should be preferred
      because of its noninvasiveness.

PMID- 19384484
TI  - Virtual MR arthroscopy of the shoulder: image gallery with arthroscopic
      correlation of major pathologies in shoulder instability.
AB  - BACKGROUND: The purpose of this study was to compare virtual MR arthroscopic
      reconstructions with arthroscopic images in patients affected by shoulder joint
      instability. MR arthrography (MR-AR) of the shoulder is now a well-assessed
      technique, based on the injection of a contrast medium solution, which fills the
      articular space and finds its way between the rotator cuff (RC) and the
      glenohumeral ligaments. In patients with glenolabral pathology, we used an
      additional sequence that provided virtual arthroscopy (VA) post-processed views,
      which completed the MR evaluation of shoulder pathology. MATERIALS AND METHODS:
      We enrolled 36 patients, from whom MR arthrographic sequence data (SE T1w and GRE
      T1 FAT SAT) were obtained using a GE 0.5 T Signa--before any surgical or
      arthroscopic planned treatment; the protocol included a supplemental 3D, spoiled
      GE T1w positioned in the coronal plane. Dedicated software loaded on a work
      station was used to elaborate VAs. Two radiologists evaluated, on a
      semiquantitative scale, the visibility of the principal anatomic structures, and
      then, in consensus, the pathology emerging from the VA images. RESULTS: These
      images were reconstructed in all patients, except one. The visualization of all
      anatomical structures was acceptable. VA and MR arthrographic images were fairly
      concordant with intraoperative findings. CONCLUSIONS: Although in our pilot study
      the VA findings did not change the surgical planning, the results showed
      concordance with the surgical or arthroscopic images.

PMID- 19384485
TI  - Hybrid external fixation for neglected fractures of the distal radius: results
      after one year.
AB  - BACKGROUND: External fixation is a well-established procedure for the treatment
      of unstable fractures of the distal radius, but its use is beset with
      complications. A plethora of theoretical and experimental data suggests that
      nonbridging fixators are superior for this setting. A new concept for the use of
      hybrid external fixation seemed reasonable and was applied for this study.
      MATERIALS AND METHODS: We report on the first 14 cases of unstable,
      extraarticular fractures of the distal radius with a one-year follow-up and
      describe the operative technique. All were treated at 3-5 weeks after injury;
      nevertheless, closed reduction after the fixator elements were fixed to the bone
      was always possible. RESULTS: We had no intraoperative complications, but in the
      follow-up period three cases of algodystrophy and one transient irritation of the
      ulnar nerve ensued. One case developed superficial infection at the K-wire entry
      site that resolved with local care and systemic antibiotics. No redisplacements
      were observed. Early and late (at one year) evaluation of results revealed good
      and very good anatomic results (Lidstrom system) and two satisfactory (cases with
      algodystrophy), eight very good and four good functional outcomes (Gartland
      Werley system). The patients' acceptance of the device was high. CONCLUSIONS:
      Hybrid external fixation of neglected distal radial fractures results in good
      outcomes if care is taken to prevent overdistraction of bone fragments.

PMID- 19384486
TI  - Flexor tendon injuries of the hand treated with TenoFix: mid-term results.
AB  - BACKGROUND: Recently, the Teno Fix device has been detailed in the literature.
      Conventional stranded cruciate repair requires splinting to protect the sutures
      from excessive loading, and then, active motion is strongly limited leading to a
      possible incomplete functional recovery. MATERIALS AND METHODS: The authors
      report on their experience in treating 21 patients presenting primary flexor
      tendon injuries within the digital sheath in zone 2, in all fingers (including
      the thumb), at an average follow-up of 16 (range: 6-26) months. RESULTS: There
      were, according to Strickland and Glogovac criteria: 12 excellent; 6 good; 3
      fair. CONCLUSIONS: This new device is practical clinically and can effect strong
      tendon repairs that withstand early active finger motion, but the best indication
      is to treat only selected cases of sharp flexor tendon lesions in zone 2. Using
      this technique it is possible to achieve a quick functional recovery and early
      return to work.

PMID- 19384488
TI  - Asymptomatic anterior shoulder dislocation of 24-year duration.
AB  - A 73-year-old woman presented with a very long-standing anterior dislocation of
      her right shoulder. She had no pain, mild impairment of active shoulder motion
      and clinical features suggesting no tear of the rotator cuff. CT 3D
      reconstructions showed a newly formed glenoid cavity below the coracoid process.
      This case indicates that an anterior shoulder dislocation lasting even decades
      may be compatible with an almost normal shoulder function.

PMID- 19384487
TI  - A study of grip endurance and strengh in different elbow positions.
AB  - BACKGROUND: The aim of our study was twofold. The first was to investigate the
      optimum position of the elbow while measuring grip endurance. The second was to
      investigate the optimum position of the elbow while measuring peak grip strength.
      The American Society of Hand Therapists advocate estimation of grip strength with
      the elbow flexed at 90 degrees with the subject in the sitting position . As far
      as we are aware, there have been no reports in English literature regarding
      studies done to evaluate the position of the elbow while measuring grip
      endurance. MATERIALS AND METHODS: A total of 45 healthy adults (16 males, 29
      females) participated in this study. A computerised handgrip analyser was used to
      measure the peak strength in the non-dominant hand, followed by measurement of
      the grip endurance. These measurements were conducted in 90 degrees of flexion
      and full extension of the elbow for each participant. RESULTS: Mean endurance in
      flexion was 71.0 N (SD 22.9) and in extension was 68.7 N (SD 27.4). Mean peak
      grip strength in flexion was 262.8 N (SD 73.1) and in extension was 264.1 N (SD
      82.0). T test analysis showed no statistical significance for elbow positions for
      grip endurance (P = 0.67) and peak gip strength (P = 0.93). CONCLUSION: Practical
      implications from this study are that grip endurance training can be undertaken
      with the elbow in 90 degrees of flexion or full extension.

PMID- 19384489
TI  - Fracture-dislocation of the shoulder and brachial plexus palsy: a terrible
      association.
AB  - Primary post-traumatic anterior dislocation of the shoulder with associated
      fracture of the greater tuberosity and brachial plexus injury is rare and, to our
      knowledge, has never previously been reported in the literature. We present a
      case of this unhappy triad in which a brachial plexus injury was diagnosed and
      treated 3 weeks later. The characteristics of this rare condition are discussed
      on the basis of our case and the published literature in order to improve early
      diagnosis and treatment of this lesion.

PMID- 19384490
TI  - Rapid resolution of femoral head osteonecrosis after rotational acetabular
      osteotomy.
AB  - The natural history of osteonecrosis of the femoral head is generally thought to
      be one of progressive deterioration if no intervention is undertaken. However, it
      is unknown whether surgical intervention is beneficial for patients with a small
      region of osteonecrosis. We observed rapid improvement of MRI findings after
      rotational acetabular osteotomy (RAO) was performed in a young patient with
      osteonecrosis of the femoral head. The band-like low signal area on T2-weighted
      images almost resolved by six months after surgery. He returned to work as an
      electrician by six months after surgery. Early surgical intervention such as RAO
      that alters the mechanical force acting on the necrotic region of the femoral
      head may accelerate the recovery of osteonecrosis and the improvement of
      symptoms.

PMID- 19384491
TI  - Retroacetabular osteolytic lesions behind well-fixed prosthetic cups: pilot study
      of bearings-retaining surgery.
AB  - BACKGROUND: Osteolytic lesions are common radiological findings behind acetabular
      prosthetic cups. If the cup is well-fixed, the management is quite controversial.
      Although implant exchange is the most reliable procedure, in most cases it could
      be considered overtreatment, with the potential for further morbidity and bone
      loss. Liner exchange associated with lesion debridement and grafting represents
      an alternative option that is less invasive. Here we present our experiences from
      a small pilot study of minimally invasive osteolysis treatment without bearings
      exchange in patients with no evidence of liner wear. MATERIALS AND METHODS: 
      INCLUSION CRITERIA: retroacetabular osteolytic lesions in ceramic-on-polyethylene
      or metal-on-polyethylene cementless total hip arthroplasties, affecting more than
      50% of the bone-prosthesis interface on anteroposterior radiography. EXCLUSION
      CRITERIA: head penetration into the liner, suspected loosening or infection. Six
      patients were selected, two asymptomatic and four symptomatic. Only the
      symptomatic patients accepted the proposed treatment (performed between June 2004
      and March 2006). All of them received fluoroscopy-assisted lesion debridement
      through an iliac cortical window, morcellized bone allograft mixed with
      autologous platelet-rich plasma, joint exploration for culture and lavage through
      a small capsular window. Patients were followed up clinically and radiologically
      at six months, 12 months, and then yearly. RESULTS: Three patients out of four
      showed clinical and radiological improvement. One showed radiological improvement
      only, and recently underwent cup exchange for subsequent loosening. The visual
      analog scale (VAS) values for pain decreased on average, but not significantly.
      No major complications occurred. No recurrence was noted at 2.25-4 years' follow
      up. CONCLUSIONS: Although the small series does not allow any absolute
      conclusions to be drawn, the reported results seem to justify further, wider
      studies. It is still unclear if osteolytic lesions associated with no wear of the
      poly liner would progress to implant failure if left untreated. Until the problem
      is better understood, this procedure might represent an interesting way to
      prevent potential loosening and severe bone loss in intact sockets.

PMID- 19384492
TI  - Health-related quality of life in patients with anterior cruciate ligament
      insufficiency undergoing arthroscopic reconstruction: a practice-based Italian
      normative group in comorbid-free patients.
AB  - BACKGROUND: Health-related quality of life (HRQoL) in anterior cruciate ligament
      (ACL) insufficiency has not been assessed in comorbid-free patients to date. An
      observational study was therefore conducted on a practice-based sample to test
      the hypothesis that SF-36 scoring in patients with chronic ACL insufficiency
      differs from the age- and gender-matched Italian norm. MATERIALS AND METHODS:
      Chronically ACL-insufficient patients with or without meniscal and/or focal
      chondral lesions were enrolled in the study. Exclusion criteria were acute ACL
      tear, severe and diffuse chondral lesions, concomitant knee major ligamentous
      injuries and/or fractures requiring surgery, previous ACL surgery and infectious,
      neoplastic and inflammatory disease. Knee function was evaluated by International
      Knee Documentation Committee (IKDC) form, HRQoL with the SF-36 questionnaire, and
      associated medical comorbidities by a Self-Administered Comorbidity Questionnaire
      (SCQ). RESULTS: A total of 316 consecutive patients, 265 males and 51 females
      (median age 25 years, range 15-52 years) met the inclusion/exclusion criteria. SF
      36 norm-based scoring showed that the Physical Functioning, Role Physical, Bodily
      Pain, and Social Functioning domains were significantly lower than the Italian
      norm; the Role Emotional domain was also lower than the norm, but the difference
      was not significant. Conversely, the General Health and Mental Health domains
      scored significantly higher than the norm; the Vitality domain also exceeded,
      albeit not significantly, the norm. CONCLUSIONS: The decision-making process
      leading to ACL reconstruction currently emphasises the evaluation of knee
      function and patients' level of activity. The findings in our study, by showing
      that chronic ACL insufficiency significantly affects HRQoL in otherwise healthy
      patients, suggest that a multidimensional evaluation including HRQoL in addition
      to knee function might be integrated into outcome assessment.

PMID- 19384494
TI  - The International Journal of Emergency Medicine: a new journal for a new era.

PMID- 19384495
TI  - State of emergency medicine in Azerbaijan.
AB  - BACKGROUND: There has been no previous study into the state of emergency medicine
      in Azerbaijan. As a legacy of the Soviet Semashko system, the "specialty" model
      of emergency medicine and integrated emergency departments do not exist here.
      Instead, pre-hospital emergency care is delivered by ambulance physicians and in
      hospital care by individual departments, often in specialty hospitals. Emergency
      care is therefore fragmented, highly specialized and inefficient. AIMS: The
      Emergency Medicine Development Initiative (EMDI) of the International Medical
      Corps (IMC) was designed to improve the quality of emergency care in four pilot
      regional centers in Azerbaijan. The objective of this study was to assess the
      baseline emergency medical capacity of these four centers. METHODS: EMDI staff
      conducted a four-part baseline survey in April 2006 to assess emergency care in
      Ganja (the second largest city in Azerbaijan), Kurdamir, Shamkir and Yevlakh.
      Data collection involved interviews with relevant personnel and a retrospective
      records review in each city. RESULTS: Pre-hospital: The number of ambulance teams
      per 10,000 inhabitants is below the number required by local regulations. On
      average, 45% of 27 medications and 37% of 17 pieces of critical equipment were
      available. Of the emergency procedures, 21% could be performed in the pre
      hospital setting. In-hospital: Admission rates were near 100% for the admissions
      department-an area that is supposed to function as an emergency department would.
      On average 57% of 40 medications and 42% of 22 pieces of critical equipment were
      available. Of the emergency procedures, 62% could be performed in the in-hospital
      setting. CONCLUSIONS: The emergency medical system surveyed in Azerbaijan is
      inefficiently organized, under-financed, poorly equipped and lacks adequately
      trained staff. Reforms need to be directed towards achieving international
      standards, while adapting new models for service delivery into the existing
      framework and improving system capacity as highlighted by this baseline
      assessment.

PMID- 19384496
TI  - Impact of health care system interventions on emergency department utilization
      and overcrowding in Singapore.
AB  - BACKGROUND: Public emergency departments (EDs) in Singapore were facing
      increasing attendances (visits) with frequent overcrowding in the 10 years from
      1975 to 1985. Over the next 12 years a series of social interventions were
      carried out to minimize "unnecessary" attendances at these EDs. AIMS: This paper
      reviews the various interventions carried out on ED utilization to determine
      their impact and usefulness. METHODS: Emergency and non-emergency attendances at
      the six main public EDs were analysed over the 32 years of the review and
      especially just before and soon after the application of four major interventions
      relating to use of EDs, including: (1) public education campaigns, (2) financial
      disincentives, (3) redirection to primary health care centres and (4) use of
      alternative clinics. RESULTS: The 12-year period of social interventions resulted
      in a fall in the proportion of non-emergency patients using the EDs from 57% to
      18%. Public education campaigns each resulted in a fall in inappropriate
      attendances of 27% to 67%. Financial disincentives were able to demonstrate an
      impact if they were significant and resulted in a heavier fiscal cost to the
      patient than if available primary health clinics were used. Redirection of non
      emergencies away from EDs resulted in significant public relations issues with
      only mild decreases in non-emergency attendances. Alternative clinics may provide
      some respite if actively promoted by ED staff, but are able to generate their own
      separate patient clientele. CONCLUSIONS: Public education and financial measures
      that seek to change the pattern of ED utilization in a community must go hand in
      hand with an easily accessible primary health care system for best effect. Co
      ordination of such efforts requires active support from all levels of the health
      service and political leadership. An active feedback loop is needed for better
      outcomes management.

PMID- 19384497
TI  - Triage Revised Trauma Score change between first assessment and arrival at the
      hospital to predict mortality.
AB  - OBJECTIVE: To assess among seriously injured accident victims whether change of
      the Triage Revised Trauma Score (T-RTS) between first assessment and arrival at
      the hospital independently predicts mortality. DESIGN: Prospective cohort study.
      METHODS: The study analysed data on 507 trauma patients with multiple injuries
      and with a Hospital Trauma Index-Injury Severity Score (HTI-ISS) of 16 or higher,
      who were presented directly by ambulance services to the Accident & Emergency
      Department of the University Medical Centre Utrecht (the Netherlands) in 1999 and
      2000. RESULTS: Compared to non-intubated patients whose T-RTS remained unchanged
      (reference category), the mortality risk was 3.1 times higher [95% confidence
      interval (CI): 1.5-6.3, p = 0.001] for patients with deteriorating T-RTS, 2.9
      times higher (95% CI: 1.3-6.5, p < 0.001) for patients who had an initially good
      T-RTS but were nevertheless intubated and 5.7 times higher (95% CI: 3.6-9.0, p <
      0.001) for patients who had an initially poor T-RTS and were intubated. These
      associations were independent of factors that could be assumed to have a direct
      effect on T-RTS, that is intravenous therapy, oxygen administration and being
      attended to by a mobile medical team at the scene of the accident. Along with T
      RTS change, more advanced age was associated with a higher mortality risk.
      CONCLUSION: Intubation and a deteriorating T-RTS between the time of the accident
      and patient's arrival at the hospital are powerful independent predictors of
      mortality after hospitalisation. Together with advanced age, a deteriorating T
      RTS should be the main aspect guiding the preclinical procedures.

PMID- 19384498
TI  - Cardiopulmonary resuscitation: outcome and its predictors among hospitalized
      adult patients in Pakistan.
AB  - INTRODUCTION: Our aim was to study the outcomes and predictors of in-hospital
      cardiopulmonary resuscitation (CPR) among adult patients at a tertiary care
      centre in Pakistan. METHODS: We conducted a retrospective chart review of all
      adult patients (age > or =14 years), who underwent CPR following cardiac arrest,
      in a tertiary care hospital during a 5-year study period (June 1998 to June
      2003). We excluded patients aged 14 years or less, those who were declared dead
      on arrival and patients with a "do not resuscitate" order. The 1- and 6-month
      follow-ups of discharged patients were also recorded. RESULTS: We found 383 cases
      of adult in-hospital cardiac arrest that underwent CPR. Pulseless electrical
      activity was the most common initial rhythm (50%), followed by asystole (30%) and
      ventricular tachycardia/fibrillation (19%). Return of spontaneous circulation was
      achieved in 72% of patients with 42% surviving more than 24 h, and 19% survived
      to discharge from hospital. On follow-up, 14% and 12% were found to be alive at 1
      and 6 months, respectively. Multivariable logistic regression identified three
      independent predictors of better outcome (survival >24 h): non-intubated status
      [adjusted odds ratio (aOR): 3.1, 95% confidence interval (CI): 1.6-6.0], location
      of cardiac arrest in emergency department (aOR: 18.9, 95% CI: 7.0-51.0) and
      shorter duration of CPR (aOR: 3.3, 95% CI: 1.9-5.5). CONCLUSION: Outcome of CPR
      following in-hospital cardiac arrest in our setting is better than described in
      other series. Non-intubated status before arrest, cardiac arrest in the emergency
      department and shorter duration of CPR were independent predictors of good
      outcome.

PMID- 19384499
TI  - Assessing risk of a prolonged QT interval-a survey of emergency physicians.
AB  - BACKGROUND: Although QT prolongation is associated with an increased risk of
      torsades de pointes (TdP), it is unclear how clinicians determine risk in
      individual patients with prolonged QT. AIMS: To investigate physicians'
      interpretation of electrocardiogram (ECG) values in patients with a prolonged QT
      in reference to risk of TdP. METHODS: A survey was sent to Australasian emergency
      physicians (EPs) to investigate interpretation of ECG data in risk assessment for
      TdP. The survey contained three sections: demographic information, questions on
      heart rate correction and six sets of ECG data which the clinician ranked from
      low to high risk. Risk analysis for ECG values was performed by producing
      histograms of the distribution of responses for each of the six sets of ECG
      parameters. These distributions were compared to predicted distributions based on
      Bazett's corrected QT > 500 ms and the QT nomogram. The QT nomogram is a recently
      developed method for assessing whether QT-HR pairs are associated with increased
      risk of TdP by plotting them to determine if they are above an at risk line-the
      nomogram. RESULTS: Of 720 surveys sent out, 249 were returned (35%). A heart rate
      correction was used by 90% of respondents and the median "at risk" QTc judged by
      EPs was 450 ms [interquartile range (IQR): 440-500 ms]. Respondents were divided
      as to whether bradycardia increased the risk of TdP, with equal numbers
      responding "no change" and "more caution". In four of the six sets of ECG
      parameters, EPs had a similar risk distribution to that predicted by Bazett. For
      one point predicted to be high risk by the QT nomogram, there was a uniform
      (undecided) risk distribution by EPs. CONCLUSIONS: EPs mainly relied on Bazett's
      correction as their method of TdP risk assessment, which may be problematic for
      bradycardic patients.

PMID- 19384500
TI  - The V-Quick patch versus the standard 12-lead ECG system: time is the essence.
AB  - INTRODUCTION: The V-Quick patch template system is compared with the standard 12
      lead electrocardiogram (ECG) acquisition technique in this paper. The objectives
      of the study were: (a) to study and compare the time taken to produce the printed
      12-lead ECG and (b) to look at the level of agreement when the ECGs were compared
      by two blinded, independent assessors. METHODS: One hundred and fifty each of
      male and female volunteers signed an informed consent form to participate in the
      clinical study. Nurses were put through a 4-h training session to familiarise
      themselves with the V-Quick patch system. The timings were measured with a
      stopwatch with the specific start and end points defined. The final ECG printouts
      were then compared by two blinded, independent assessors for several set
      criteria. RESULTS: The V-Quick patch system was proved to be significantly faster
      than the standard 12-lead system in the acquisition of the ECG in both male and
      female volunteers. The time taken in male volunteers was also noted to be
      significantly faster than in female volunteers. CONCLUSION: The two assessors
      shared a 100% agreement level when comparing the ECGs acquired by both techniques
      in the same individual (intra-assessor agreement) and when each ECG was read by
      the two assessors separately (inter-assessor agreement).

PMID- 19384501
TI  - Meningococcemia.

PMID- 19384502
TI  - Sats in the 60s.

PMID- 19384503
TI  - Traumatic pneumorrhachis: a rare entity of trauma.

PMID- 19384504
TI  - EMcounter-charting the epidemiology of medical emergencies in India: a status
      report.
AB  - BACKGROUND: In the last decade, the specialty of Emergency Medicine has gained
      tremendous interest in low and middle income countries, with a demand for new
      training programs, pre-hospital systems, emergency department expansions and
      policy change. Yet, little is known about the actual distribution of medical
      emergencies in these settings. AIM: Project EMcounter proposes the implementation
      of this much needed, uniform, multi-center epidemiologic survey of emergencies in
      India to provide sound scientific data upon which new training programs,
      infrastructural expansions, and legislative change can be built. METHODOLOGY: A
      standardized, web-based, user-friendly data entry tool, EMcounter, forms the
      backbone of this project. The tool is currently piloted at a tertiary center in
      Chennai, India. The project is aimed at capturing the geographic and temporal
      variations in over 20 participating centers across the private and public sector
      in rural and urban India. The uniform use of the web-based tool ensures
      standardization in data collection across the centers. Our pilot project logs
      patient demographics, pre-hospital transportation, chief complaints, vitals,
      interventions, disposition and diagnoses. The volume of data thus collected is
      large and is currently saved in a spread sheet format. OBSERVATIONS: The first
      quarter has already begun to highlight the epidemiologic differences between a
      local hospital in Chennai and national averages in the US. The pilot phase has
      been critical in gauging the robustness of the tool before its expansion to
      multiple centers and has proved to be invaluable in identifying potential flaws.
      CONCLUSION: The early pilot phase has demonstrated that combining the multiple
      parameters available through the EMcounter database will allow the study of
      demographics and existing practice algorithms. Expansion of the project to
      multiple centers will shed objective light on the gaps in health-care provision
      at various levels and help design triage and transfer guidelines based on these
      data. This epidemiologic knowledge can potentially have significant influence in
      shaping the inventories and designs of emergency departments, and identifying
      staff needs and skill requirements. The project aims to seek and analyze data
      that will make the development of emergency medicine in India locally relevant.

PMID- 19384505
TI  - 'Pseudopneumothorax'-hold that chest tube!
AB  - We report a case of herniation of abdominal contents into the left hemithorax in
      a patient with a history of vague left-sided thoracoabdominal trauma 18 days
      previous to admission and who also had a recent 1-week history of upper
      respiratory symptoms, including cough, and then presented with dyspnoea and fever
      for 3 days. There was no preceding cardiorespiratory pathology of note. We also
      discuss the epidemiology, pathogenesis and management of blunt-traumatic
      diaphragmatic rupture.

PMID- 19384506
TI  - Emergency medicine in Italy today: just like the USA in 1968.

PMID- 19384508
TI  - Application of lean thinking in health care: a role in emergency departments
      globally.

PMID- 19384509
TI  - A perspective on developing emergency medicine as a specialty.
AB  - AIMS: A rapidly increasing number of countries are developing their capacities to
      respond to acute illness and injury and organizing emergency medicine training
      programs. This article offers some insight into the way emergency medicine has
      undergone development in the Australasian region. METHODS: The perspective is
      built from experience in Australia, New Zealand and Papua New Guinea. CONCLUSION:
      The challenges are many, but with persistence can be surmounted. Lessons derived
      from these diverse environments are presented.

PMID- 19384510
TI  - Incidence and impact of undisclosed cocaine use in emergency department chest
      pain and trauma patients.
AB  - BACKGROUND: One of the highest rates of illicit cocaine consumption in Europe is
      in Spain. Our objective was to study the incidence and impact of undisclosed
      cocaine consumption in patients attending the emergency department (ED) for
      trauma or chest pain. METHODS: We analysed urine samples from consecutive
      patients attending the ED for trauma or chest pain to determine the presence of
      cocaine, cannabis, amphetamine/metaamphetamine and opioids by semiquantative
      tests with fluorescence polarization immunoassay (FPIA). RESULTS: Thirty percent
      of eligible patients participated. Of 75 cases, 61.3% had trauma and 38.7% chest
      pain; 25% presented a positive test for drugs. Cocaine was present in 13.3% and
      cannabis in the same proportion. No differences were found regarding positive
      cocaine test and chief complaint, ED or hospital stay, or additional tests.
      Cocaine-positive patients were significantly younger.

PMID- 19384511
TI  - Safety of procedural sedation and analgesia in children less than 2 years of age
      in a pediatric emergency department.
AB  - BACKGROUND: Although young age is considered a risk factor for adverse events
      related to procedural sedation and analgesia (PSA), data in very young children
      (<2 years of age) are lacking. AIMS: The main objective of our study is to
      describe PSA in children <2 years of age in an inner city tertiary care pediatric
      emergency department (PED). METHODS: We conducted a retrospective chart review
      from January 2005 to June 2007 of children <2 years of age who received PSA in
      our PED. We collected demographic variables, indication for and medications used
      for PSA, adverse events (AE) related to PSA, and interventions performed to treat
      them. RESULTS: Of the children who received PSA, 14.5% (180/1,235) were <2 years
      of age of whom 173 were included for the analysis; 73% (126/173) of the study
      subjects were between 1 and 2 years of age, 54.3% (94/173) were male, and 96.5%
      (167/173) belonged to American Society of Anesthesiologists class 1. Incision and
      drainage (45.0%, 78/173) and laceration repair (32.4%, 56/173) were the two most
      common indications for PSA. Ketamine and midazolam was the most common
      combination medication used for PSA (62.4%, 108/173). Sedation was deemed
      ineffective in 5.8% (10/173) of the children. There were only two failed
      sedations; 5.8% (10/173) of the children experienced AE with most being minor
      [oxygen desaturations 1.7% (3/173), emesis 2.3% (4/173), and others 1.2%
      (2/173)]. One child experienced serious AE in the form of apnea and bradycardia
      requiring intubation. CONCLUSIONS: Our data suggest that children under 2 years
      of age can be sedated effectively without increased risk of AE in a PED.

PMID- 19384512
TI  - Prospective study of patients with altered mental status: clinical features and
      outcome.
AB  - AIMS: Patients with altered mental status (AMS) present commonly to the Emergency
      Department (ED). The aim of this prospective study is to identify the various
      clinical features of this diverse group of patients and trace their outcomes.
      This will allow clinicians to be aware of the natural history of the symptom
      complex and the difficulties in managing them. METHODS: In this prospective
      observational study, we recruited patients aged 18 and above diagnosed with AMS
      at Tan Tock Seng Hospital ED from December 2006 to October 2007. This is an urban
      ED. Demographic, clinical, radiology, laboratory data, final diagnosis and length
      of stay were collected from their entry into the ED till discharge or demise
      using the ED's and inpatient electronic records. RESULTS: From December 2006 to
      October 2007, 967 patients with a mean age of 66.5 years diagnosed with AMS were
      recruited into our study. The total number of CT scans done during the study
      period was 674, of which 246 (37%) were abnormal and 428 (63%) were normal. The
      mean hospital length of stay was 11.6 days. Patients with abnormal CT results
      stayed longer than those whose results were normal (median of 9 days versus
      median of 6 days). The three most common causes of AMS in our study population
      were of neurological (34.4%), infectious (18.3%) and metabolic (12%) aetiologies.
      Overall, 106 (11%) patients died during hospitalisation; 36 (33.9%) and 39
      (36.8%) deaths were attributed to ischaemic stroke and haemorrhagic stroke,
      respectively. CONCLUSIONS: AMS remains a symptom complex that carries a
      significant length of hospital stay and mortality. The most common causes of AMS
      are those that require timely intervention and are highly treatable. This study
      will provide insight into proper allocation of resources to manage this group of
      patients, from triaging to investigations and treatment at the ED and inpatient
      levels.

PMID- 19384513
TI  - Focused abdominal sonography for trauma in the emergency department for blunt
      abdominal trauma.
AB  - BACKGROUND: Blunt abdominal trauma (BAT) is a diagnostic challenge to the
      emergency physician (EP). The introduction of bedside ultrasound provides another
      diagnostic tool for the EP to detect intra-abdominal injuries. AIMS: To evaluate
      the performance of EP in a local emergency department in Hong Kong to perform the
      'focused abdominal sonography for trauma' (FAST) in BAT patients. METHODS: This
      was a retrospective cohort study including all the trauma team cases in a 36
      month period in the emergency department of a public hospital in Hong Kong. The
      results of FAST scans were analyzed and compared with CT scans when the FAST was
      positive or followed by a period of clinical observation when the FAST was
      negative. Descriptive statistics and sensitivity, specificity, and predictive
      values were calculated. RESULTS: There was a total of 273 cases, and FAST scans
      were performed in 242 cases. The sensitivity and specificity were 86% and 99%,
      respectively. The negative predictive value was 0.98, while the positive
      predictive value was 0.94. The overall accuracy was 97%. CONCLUSIONS: The
      performance of the EP in using FAST scans in BAT patients was encouraging. The
      high specificity (99%), positive predictive value (0.98), and likelihood ratio
      for positive tests (86) make it a good 'rule in' tool for BAT patients. The high
      negative predictive value also makes the FAST scan a useful screening tool.
      However, ultrasound examination is operator dependent, and FAST scan has its own
      limitations. For negative FAST scan cases, we recommend a period of monitoring,
      serial FAST scans, or further investigations, such as CT scan or peritoneal
      lavage.

PMID- 19384514
TI  - The impact of process re-engineering on patient throughput in emergency
      departments in the UK.
AB  - BACKGROUND: The re-engineering of emergency department (ED) processes in the UK
      since 2002 has produced significant reductions in waiting times. AIMS: We aim to
      describe the generic themes contributory to this improvement in performance,
      which has led to progress not yet replicated elsewhere in the English-speaking
      world. METHODS: We reviewed the Emergency Services Collaborative (ESC) set up by
      the National Health Service (NHS) Modernisation Agency as well as our own
      departmental performance in order to identify key themes for discussion. In
      addition, we reviewed relevant information from the UK Department of Health
      website. We used the 4-h target of patient passage through the ED as our primary
      outcome measure. RESULTS: Early results from the ESC showed improvements, which
      have been sustained and enhanced since inception. We use our hospital performance
      figures to demonstrate a pattern of progressive improvement in performance, with
      99.1% of all new attenders in 2007-2008 being seen, treated and discharged or
      admitted within 4 h of presentation to the ED. CONCLUSIONS: The whole systems
      approach to re-engineering emergency care has led to universal improvements in
      patient throughput in EDs in the UK. Several of the concepts found to be useful
      in the NHS are worthy of consideration and adoption by other health care systems.
      Long waits in the ED are a thing of the past in the UK.

PMID- 19384515
TI  - Development of an ultrasound training curriculum in a limited resource
      international setting: successes and challenges of ultrasound training in rural
      Rwanda.
AB  - BACKGROUND: Over the last decade, the diffusion of ultrasound technology to
      nontraditional users has been rapid and far-reaching. Much research and effort
      has been focused on developing an ultrasound curriculum and training and practice
      guidelines for these users. The potential for this diagnostic tool is not limited
      to the developed world and in many respects ultrasound is adaptable to limited
      resource international settings. However, needs-based curriculum development,
      training guidelines, impact on resource utilization, and sustainability are not
      well studied in the developing world setting. AIMS: We review one method of
      introducing applicable curriculum, training local providers, and sustaining a
      comprehensive ultrasound program. METHODS: Two rural Rwandan hospitals affiliated
      with a US nongovernmental organization participated in a pilot ultrasound
      training program. Prior to introduction of ultrasound, local physicians completed
      a survey to determine the perceived importance of various ultrasound scan types.
      Hospital records were also reviewed to determine disease and presenting complaint
      prevalence as part of an initial needs assessment and to define our curriculum.
      We hypothesized certain studies would be more utilized and have a greater impact
      given available treatment resources. RESULTS: We review here the choice of
      curriculum, the training plan, helpful equipment specifications, and
      implementation of ongoing measures of quality assessment and sustainability. Our
      9-week lecture and practice-based ultrasound curriculum included obstetrics,
      abdominal, renal, hepatobiliary, cardiac, pleural, vascular, and procedural
      ultrasound. CONCLUSIONS: While ultrasound as a diagnostic modality for resource
      poor parts of the world has generated interest for years, recent advances in
      technology have brought ultrasound again to the forefront as a sustainable and
      high impact technology for resource-poor developing world nations. From our
      experience in rural Rwanda, we conclude that ultrasound remains helpful in
      patient care and the diagnostic impact is enhanced by choosing the correct
      applications to implement. We also conclude that ultrasound is a teachable skill,
      with a several week intensive training period involving hands-on practice skills
      and plans for long-term learning and have begun a second phase of evaluating
      knowledge retention for this introductory program.

PMID- 19384516
TI  - Understanding statistical tests in the medical literature: which test should I
      use?

PMID- 19384517
TI  - Transport time to trauma facilities in Karachi: an exploratory study.
AB  - BACKGROUND: Rapid urban growth in developing countries has outpaced the
      development of health infrastructure, including trauma centers, leading to
      potential delays in trauma care. This study was conducted in Karachi, a city of
      16 million people in Pakistan. AIMS: Our aim was to determine the time taken to
      reach the nearest 24-h emergency care facility (ECF) and the government
      designated trauma center (TC). We also sought to determine the availability of
      supplies and equipment required for "basic" trauma care at these centers.
      METHODS: We selected five towns in Karachi that had the highest number of road
      traffic injuries (RTIs) (as identified through medicolegal records). We then
      measured the time taken to reach the nearest ECF and the government-designated TC
      from four compass points within each town. We also asked about the equipment and
      supplies used in basic trauma care. RESULTS: All three TCs in Karachi were
      located in the selected towns and were within 5.0-10.5 km of each other. The
      transport times to the 3 TCs were an average of 13.3 min (+/- 7.1) and to the 16
      ECFs an average of 4.7 min (+/- 2.4) (p value < 0.00). Most ECFs did not have all
      equipment and supplies necessary for basic trauma care; 90% had the basic
      equipment for management of airway, oxygen, and IV fluids, 70% had morphine, and
      45% had C-spine collars. CONCLUSIONS: Vital time is lost in reaching a government
      designated TC. ECFs might be an alternative option, but are not fully equipped
      and funded to provide adequate trauma care to all.

PMID- 19384518
TI  - Early onset muscarinic manifestations after wild mushroom ingestion.
AB  - Despite being a favorite delicacy, only 200-300 of the 5,000 known mushroom
      species have been clearly established to be safe for consumption. Cases of
      mushroom poisoning have been reported with diverse clinical syndromes. A
      syndromic classification of mushroom poisoning has recently been developed to
      facilitate early interventions. We present a series of five cases of mushroom
      poisoning with muscarinic manifestations to highlight the difficulties we faced
      with exact species and toxin identification and the importance of this syndromic
      classification. The common symptoms in our case series are blurred vision,
      diarrhea, vomiting, and abdominal cramps.

PMID- 19384519
TI  - Bispectral index monitoring during cardiopulmonary resuscitation repeated twice
      within 8 days in the same patient: a case report.
AB  - Research on cardiac resuscitation has led to various changes in the techniques
      and drug administration involved in modern advanced life support. Besides
      improving primary cardiac survival, interest is increasingly focused on a
      favourable neurological outcome. However, until now there has been no on-site
      equipment to support the clinical observations of the cardiopulmonary
      resuscitation (CPR) team. Bispectral index (BIS) monitoring has been used for
      avoiding awareness during anaesthesia for many years. We report a case of a 68
      year-old patient suffering twice from cardiac arrest due to thromboembolism
      within a few days. While the first cardiac resuscitation was survived without
      neurological consequences, the patient died after the second event. Both
      resuscitation events were monitored using the BIS. We discuss the course of BIS
      values and their possible contribution to the prediction of outcome.

PMID- 19384520
TI  - The utility of cardiac sonography and capnography in predicting outcome in
      cardiac arrest.
AB  - Emergency physicians and intensivists are increasingly utilizing capnography and
      bedside echocardiography during medical resuscitations. These techniques have
      shown promise in predicting outcomes in cardiac arrest, and no cases of return of
      spontaneous circulation in the setting of sonographic cardiac standstill and low
      end-tidal carbon dioxide have been reported. This case report illustrates an
      example of such an occurrence. Our aims are to report a case of return of
      spontaneous circulation in a patient with sonographic cardiac standstill,
      electrocardiographic pulseless electrical activity, and low end-tidal carbon
      dioxide tensions and to place the case in the context of previous literature on
      this topic. Case report and brief review of the literature. In 254 cases
      reported, no patient has survived in the setting of sonographic cardiac
      standstill and low end-tidal carbon dioxide tension, making the reported case
      unique. This case should serve to illustrate the utility and limitations of
      combined cardiac sonography and end-tidal carbon dioxide measurement in
      determining prognosis during cardiac arrest.

PMID- 19384521
TI  - Torsade de pointes caused by polypharmacy and substance abuse in a patient with
      human immunodeficiency virus.
AB  - Drug-induced QT prolongation is a potentially dangerous adverse effect of some
      medication combinations. When QT prolongation progresses to torsade de pointes,
      life-threatening or fatal outcomes may result. A 57-year-old man with a history
      of human immunodeficiency syndrome on abacavir, nevirapine, tenofovir,
      voriconazole, and methadone presented to the emergency department with a chief
      complaint of new-onset seizures. The physical exam was unremarkable. The
      electrocardiogram demonstrated sinus bradycardia and a prolonged QT(c) interval
      of 690 ms. In the emergency department, he had several episodes of torsade de
      pointes (TdP) and ventricular tachycardia that resolved spontaneously. These
      episodes were accompanied by an alteration in mentation and generalized
      twitching. Magnesium and amiodarone were effective in terminating the
      dysrhythmia. The patient had multiple risk factors for prolonged QT syndrome
      including human immunodeficiency virus infection, methadone therapy, and
      polypharmacy leading to potential drug interactions. Physicians must be aware of
      multidrug interactions potentiating QT prolongation and leading to torsade de
      pointes.

PMID- 19384522
TI  - Malpositioning of a nasogastric tube: a pitfall in the emergency department.

PMID- 19384523
TI  - Leriche syndrome.

PMID- 19384524
TI  - Chest pain in an adolescent male.

PMID- 19384525
TI  - Complex metacarpophalangeal dislocation.

PMID- 19384526
TI  - Spontaneous pneumomediastinum.

PMID- 19384527
TI  - Acute renal infarction.

PMID- 19384528
TI  - Enhancing the research experience through peer-reviewed literature.

PMID- 19384531
TI  - [Septic organ failure and cellular malfunction].

PMID- 19384532
TI  - [Pathomechanisms of organ failure. Mitochondrial dysfunction in sepsis].
AB  - Proinflammatory mediators as well as increased formation of reactive oxygen and
      nitrogen species impair cellular respiration during sepsis. In particular, the
      highly reactive peroxynitrite irreversibly damages lipids, proteins and nucleic
      acids and also inhibits enzyme complexes of the respiratory chain. In this way
      cellular metabolic functions and subsequently organ functions are also impaired.
      Repair of DNA by poly(ADP-ribose)polymerase consumes large amounts of
      nicotinamide adenine dinucleotide (NAD+) which leads to cellular NAD+ depletion
      further promoting inflammation. This article summarizes central aspects of the
      pathophysiology of mitochondrial dysfunction during sepsis and gives an overview
      about newly developed strategies which proved effective in experimental studies
      and may have a potential clinical application in the future.

PMID- 19384533
TI  - [Intracranial pressure-volume relationship. Physiology and pathophysiology].
AB  - Posttraumatic increase of intracranial pressure (ICP) is a strong prognostic
      factor for the outcome of patients after traumatic brain injury. After exhausting
      all compensatory mechanisms ICP increases exponentially, where ICP(norm)=(CSF
      production*CSF flow resistance)+venous pressure((sinus sagittalis))=10-15 mmHg.
      The ICP curve is influenced by the compliance (DeltaV/DeltaP) and elasticity
      (DeltaP/DeltaV) of the brain. Marmarou could demonstrate that the non-linear
      cranio-spinal pressure-volume relationship describes a logarithmic, mono
      exponential, strongly linear relationship between pressure and volume and named
      this the pressure volume index (PVI=log ICP/DeltaV). The pressure volume index
      describes the volume necessary to increase ICP by a factor of 10. Additionally to
      PVI the measurement of volume-pressure response (VPR) was introduced. The
      continuous intracranial compliance could be determined on the principle of
      pulsatile volume increases as an equivalent of very small intra-cranial volume
      increases. However, to ascertain functional status of the injured brain a
      combination of measurements of different parameters, such as tissue oxygen
      partial pressure (p(ti)O2), cerebral blood flow (CBF), microdialysis and
      electrocorticography (ECoG) is recommended.

PMID- 19384534
TI  - [Monitoring intracranial pressure. Indication, limits, practice].
AB  - The function of the brain is not checkable in comatose or sedated patients.
      Because secondary brain damage will often cause brain edema it is necessary to
      recognize the resulting increases in brain pressure. Therefore, measurement of
      intracranial brain pressure (ICP) is the standard monitoring procedure in
      neurological intensive care. The procedure with a small drill hole trepanation
      and the insertion of a micropressure sensor has a comparatively low complication
      rate and offers continuous monitoring with reliable values. Other neuro
      monitoring procedures have not achieved the value of ICP measurement and only
      reflect changes in ICP with other measurement principles. ICP measurement is the
      procedure which is decisive for conservative measures in the intensive care unit
      to secure cerebral perfusion or indications for surgical treatment of brain
      edema. Central venous pressure, intra-abdominal pressure and positive end
      expiratory pressure do not have a substantial influence on ICP.

PMID- 19384535
TI  - [Anesthesia in ambulatory patients].
AB  - The share of ambulatory procedures is increasing with advances in operative and
      anesthesiological methods and pressured by economical necessities. Following
      legal regulations procedures with and without hospital stay underlie the same
      quality measures. Multimodal concepts comprising anesthesiological and operative
      procedures, pain therapy as well as postoperative care allow for quality
      improvements in respect to operative outcome and patient satisfaction.

PMID- 19384536
TI  - [Efficacy and patient benefit of treatment of irritated skin with ointments
      containing dexpanthenol: health services research (observational study) on self
      medication in a pharmaceutical network].
AB  - BACKGROUND: Products containing dexpanthenol are used to treat irritated and
      inflamed skin. So far there is a lack of data for the evidence of patient
      relevant benefits. OBJECTIVE: Assessment of the patient-relevant benefit of
      ointments containing dexpanthenol in the self-medicated therapy of irritated
      skin. METHODS: Prospective, observational study in a network of 392 pharmacies.
      Consecutive recruitment of n=1,886 patients with symptoms of irritated skin,
      including non-inflammatory intervals of atopic eczema, other xerotic skin
      conditions and impairment of skin barrier. The patient-relevant benefit was
      ascertained prior to and 7-10 days after treatment through the patient-benefit
      index (PBI). RESULTS: The PBI showed that 91.5% of the patients experienced a
      relevant benefit from treatment. 94.7% directly indicated to have had achieved
      successful therapeutic results. All symptoms of irritated skin (e.g. xerosis,
      erythema, desquamation) significantly improved (p<or=0,001). The subjective
      response was independent of age, gender and underlying skin disease. CONCLUSION:
      High patient-relevant benefits were observed in the treatment of irritated skin
      with dexpanthenol ointment.

PMID- 19384537
TI  - [Optical coherence tomography in middle ear surgery].
AB  - The application of optical coherence tomography (OCT) in middle ear surgery has a
      high diagnostic potential, especially for intraoperative evaluation of the cause
      of stapes fixation, intraoperative assessment of the morphology of the stapes
      footplate in revision stapes surgery, and as an orientation guide in cochlear
      implantation in congenital anomalies. OCT displays the middle and inner ear
      structures precisely. This technology enables the surgeon to use this information
      for further specification of the intraoperative modus operandi. Considering our
      own in vivo and ex vivo investigations and animal experiments, potential areas of
      application can be defined: visualization of the oval window niche in revision
      stapesplasty and reconstructive middle ear surgery, as well as during explorative
      tympanotomy for intraoperative assessment of perilymph fistula, and demonstration
      of structures of the exposed but not opened inner ear.

PMID- 19384538
TI  - [Stapes surgery : first experiences with the new Soft-CliP piston].
AB  - BACKGROUND: The first hearing results with a new stapes prosthesis with clip
      function (Soft-CliP(R) piston) are presented. PATIENTS AND METHODS: This new
      prosthesis was used in 15 patients (mean age 45.2 years; range 21-63 years)
      undergoing routine stapes surgery. Soft-CliP(R) piston prostheses with a shaft
      diameter of 0.4 mm and a length ranging from 4.25 mm to 5.5 mm were used.
      Postoperative audiological testing and measurement of the air-bone gap were
      performed after an average of 47.3 days and compared with the preoperative
      values. RESULTS: The median observed postoperative air-bone gap (ABG) was 8.33 dB
      +/-4.16 dB. All patients had less than 20 dB ABG and in 53.3% of cases was less
      than 10 dB. The operating time showed a clear difference between the left (66.5
      min +/-37.79 min) and right ears (47.2 min +/-11.08 min). DISCUSSION: This new
      prosthesis design greatly facilitates a very difficult step in stapes surgery,
      the prosthesis fixation to the incus. The first postoperative hearing results are
      very promising but long-term results in a larger group of patients are still
      pending.

PMID- 19384539
TI  - [Histiocytosis of Langerhans cells. Simultaneous manifestation in both mastoid
      cavities].
AB  - Histiocytosis X (Langerhans cells) is a rare disease with different forms of
      manifestation in the head and neck, which mostly occurs in children. We report
      the case of a 52-year-old male patient from Saudi Arabia who presented in the out
      patient department of the University Hospital Charite Berlin with therapy
      resistant otitis externa. ENT examination additionally showed nasal polyps. A
      paranasal computed tomography scan revealed as an incidental finding a mass
      forming tumor in both mastoids with osseous destruction of the posterior cranial
      fossa. Histological evaluation of the suspected tissue revealed histiocytosis X
      in both mastoids. After exclusion of a systemic disease local low-dose
      radiotherapy with 9 Gy (3x3 Gy) of the mastoid cavities was administered.

PMID- 19384540
TI  - [Multifocal manifestation of Rosai-Dorfman disease. A rare case of purely
      extranodal sinus histiocytosis in the elderly].
AB  - Rosai-Dorfman disease belongs to the group of childhood histiocytoses and was
      initially described as sinus histiocytosis with massive lymphadenopathy. Its rare
      purely extranodal manifestation is primarily found in the head and neck region.
      An atypical primary manifestation in an elderly patient with multifocal
      extranodal disease is described, and this pathological entity is reviewed.
      Specific difficulties concerning differential diagnostic aspects as well as
      individually appropriate treatment strategies are discussed.

PMID- 19384541
TI  - [Laryngeal lead shot injury: therapy and follow-up].
AB  - Laryngeal shot injuries are rare. The case of a 65-year-old man who suffered from
      an injury with lead pellets is reported. After exploration with removal of the
      pellet from the lateral cricoarytenoid muscle, an immobility of the vocal fold
      developed, accompanied by impaired vocal function. Despite persisting immobility
      of the vocal fold, after 12 weeks voice compensation was achieved by voice
      therapy.

PMID- 19384542
TI  - [Therapeutic management of dislocated laryngeal fractures].
AB  - BACKGROUND: Acute trauma with laryngeal fracture is a rare injury affecting all
      functions of the larynx. Resuscitation follows the ABC principles for acute
      trauma life support. The priority has always been the establishment of an
      adequate and secure airway. To achieve optimal therapeutic long-term results,
      permanent stabilisation of the airway and good functional restoration of
      phonation and swallowing are necessary. We describe the therapy and long-term
      follow-up of two patients who suffered laryngeal fracture. CASE REPORTS: The
      first case concerns a 31-year-old woman who suffered polytrauma with
      laryngotracheal separation in a car accident. The fracture was reduced and fixed
      utilizing miniplates. After decannulation the patient had a patent airway. She
      regained normal voice and was able to swallow without difficulty. The other case
      concerns a 16-year-old boy who suffered a laryngeal fracture in a bicycle
      accident. He also underwent subsequent operative therapy using adaptation plates.
      This patient also regained an adequate airway and a good postoperative voice.
      There were no problems with swallowing. CONCLUSION: Chondrosynthesis with
      adaptation plates provides an enduring and exact fixation of laryngeal fractures.
      In the long term, this leads to a stable recovery of function concerning airway,
      voice, and swallowing.

PMID- 19384545
TI  - [Acute brain stem syndromes].
AB  - The brain stem consists of the mesencephalon, pons, and medulla oblongata and
      contains the nuclei of the cranial nerves III to XII, their complex connectivity,
      the ascending and descending fibre tracts, and the cerebellar connections. The
      corticobulbar and corticospinal tracts and the medial lemniscus cross its
      midline. Vital functions such as wakefulness, respiration, swallowing, and
      circulation are controlled there. Here we discuss acute brain stem syndromes of
      vascular, inflammatory, and toxic-metabolic origin. They present frequently with
      alternating symptoms, i.e. ipsilateral cranial nerve deficits associated with
      contralateral signs of long-fibre tract involvement and with various disturbances
      of the oculomotor system. Modern diagnostic and therapeutic approaches are
      described along with clinical presentation.

PMID- 19384543
TI  - [Nobel price for vaccination against cervical cancer: current data and
      guidelines].
AB  - Harald zur Hausen received the Nobel price for Medicine in 2008 for his seminal
      research on human papilloma viruses and their association with anogenital
      diseases. On the basis of his work highly effective prophylactic vaccines have
      been developed. Clinical studies have shown nearly 100% seroconversion and an
      excellent safety profile as well as greater than 96% efficacy against HPV
      infection and premalignant dysplasia, induced by HPV types covered by the
      vaccine. Due to the convincing data of phase II and III clinical trials the
      introduction of HPV vaccination was recommended by health authorities and
      scientific committees in Germany. The development and availability of guidelines
      and evidence-based recommendations should support the introduction of the vaccine
      and widespread vaccination.

PMID- 19384546
TI  - Surface-enhanced Raman scattering: realization of localized surface plasmon
      resonance using unique substrates and methods.
AB  - Surface-enhanced Raman scattering (SERS) enhancement and the reproducibility of
      the SERS signal strongly reflect the quality and nature of the SERS substrates
      because of diverse localized surface plasmon resonance (LSPR) excitations excited
      at interstitials or sharp edges. LSPR excitations are the most important
      ingredients for achieving huge enhancements in the SERS process. In this report,
      we introduce several gold and silver nanoparticle-based SERS-active substrates
      developed solely by us and use these substrates to investigate the influence of
      LSPR excitations on SERS. SERS-active gold substrates were fabricated by
      immobilizing colloidal gold nanoparticles on glass slides without using any
      surfactants or electrolytes, whereas most of the SERS-active substrates that use
      colloidal gold/silver nanoparticles are not free of surfactant. Isolated
      aggregates, chain-like elongated aggregates and two-dimensional (2D)
      nanostructures were found to consist mostly of monolayers rather than
      agglomerations. With reference to correlated LSPR and SERS, combined experiments
      were carried out on a single platform at the same spatial position. The isolated
      aggregates mostly show a broadened and shifted SPR peak, whereas a weak blue
      shifted peak is observed near 430 nm in addition to broadened peaks centered at
      635 and 720 nm in the red spectral region in the chain-like elongated aggregates.
      In the case of 2D nanostructures, several SPR peaks are observed in diverse
      frequency regions. The characteristics of LSPR and SERS for the same gold
      nanoaggregates lead to a good correlation between SPR and SERS images. The
      elongated gold nanostructures show a higher enhancement of the Raman signal than
      the the isolated and 2D samples. In the case of SERS-active silver substrates for
      protein detection, a new approach has been adopted, in contrast to the
      conventional fabrication method. Colloidal silver nanoparticles are immobilized
      on the protein functionalized glass slides, and further SERS measurements are
      carried out based on LSPR excitations. A new strategy for the detection of
      biomolecules, particularly glutathione, under aqueous conditions is proposed.
      Finally, supramolecular J-aggregates of ionic dyes incorporated with silver
      colloidal aggregates are characterized by SERS measurements and correlated to
      finite-difference time-domain analysis with reference to LSPR excitations.

PMID- 19384547
TI  - Test-retest variability of quantitative [11C]PIB studies in Alzheimer's disease.
AB  - PURPOSE: The aim of this study was to assess the test-retest variability of
      [11C]PIB studies in patients with Alzheimer's disease (AD) and healthy controls
      using several tracer kinetic models and to assess the suitability of the
      cerebellum as reference tissue. METHODS: [11C]PIB studies with arterial sampling
      were performed in eight AD patients and eight healthy controls. Retest scans were
      performed in six controls and six AD patients. Data were analysed using plasma
      input and reference tissue models, together with simple ratios. RESULTS: Test
      retest variability was best ( approximately 3%) for SRTM2, a parametric method
      based on the simplified reference tissue model. Highest values ( approximately
      10%) were found for plasma input models. Cerebellar V(T) values did not differ
      significantly between AD and controls. CONCLUSION: Parametric SRTM2 with the
      cerebellum as reference tissue is the method of choice for quantitative analysis
      of [11C]PIB PET studies.

PMID- 19384548
TI  - Atherosclerotic plaque volume and composition in symptomatic carotid arteries
      assessed with multidetector CT angiography; relationship with severity of
      stenosis and cardiovascular risk factors.
AB  - The purpose of this study was to examine the volume and the composition of
      atherosclerotic plaque in symptomatic carotid arteries and to investigate the
      relationship between these plaque features and the severity of stenosis and the
      presence of cardiovascular risk factors. One hundred patients with
      cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV)
      and the relative contribution of plaque components (calcifications, fibrous
      tissue, and lipid) in the symptomatic artery. The contribution of different
      components was measured as the number of voxels within defined ranges of HU
      values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU).
      Fifty-seven patients had atherosclerotic plaque in the symptomatic carotid
      artery. The severity of stenosis and PV were moderately correlated. Age and
      smoking were independently related to PV. Patients with hypercholesterolemia had
      significantly less lipid and more calcium in their plaques than patients without
      hypercholesterolemia. Other cardiovascular risk factors were not significantly
      related to PV or plaque composition. Luminal stenosis of the carotid artery
      partly reflects the amount of atherosclerotic carotid disease. Plaque volume and
      plaque composition are associated with cardiovascular risk factors.

PMID- 19384550
TI  - [Regenerative potential of human adult precursor cells: cell therapy--an option
      for treating cartilage defects?].
AB  - Cell-based therapeutical approaches are already in clinical use and are
      attracting growing interest for the treatment of joint defects. Mesenchymal stem
      and precursor cells (MSC) cover a wide range of properties that are useful for
      the regeneration process of bone and cartilage defects. The following article is
      an overview of the regenerative potential of MSC and discusses how the properties
      of these cells can be used for the development of new strategies in regenerative
      medicine.

PMID- 19384549
TI  - [B-cell-targeted therapy in the treatment of autoimmune diseases].
AB  - In recent years a growing body of evidence suggests a more central role for B
      cells in the pathogenesis of several autoimmune diseases, apart from being the
      precursors of autoantibody-producing plasma cells. B-lymphocytes play an
      important role in the pathogenesis of various autoimmune diseases. In particular,
      the introduction of rituximab, a depleting antibody targeting CD20+ B cells and
      its clinical efficacy in rheumatoid arthritis, systemic lupus erythematosus,
      vasculitis and multiple sclerosis has stimulated further B-cell-targeted
      therapies. Other biologicals targeting CD20 are under clinical investigation. New
      strategies include targeting further B-cell surface markers such as CD22, as well
      as blocking B-cell-activating factors or their receptors.

PMID- 19384551
TI  - [Mesenchymal stem cells in arthritis].
AB  - While one of the major achievements of the 20th century was prolonging life
      expectancy in developed countries, the main challenge of the 21st century is to
      improve the quality of life of the aging population. Aging is associated with a
      progressive reduction of organ system function. Therefore, regenerative medicine
      will be one of the major developing fields of medicine. This new medical field
      does not only apply to aging but also to all degenerative diseases, such as
      arthritis and degenerative joint disease, which lead to progressive degeneration
      of mesenchymal tissues such as bone and cartilage. The discovery of pluripotent
      mesenchymal stem cells (MSCs) offers a promising alternative to surgery for non
      invasive regenerative therapies of mesenchymal tissues. This review focuses on
      the characterization and potential application of MSCs in the regeneration of
      damaged joints.

PMID- 19384552
TI  - [Therapeutic application of mesenchymal stromal cells in autoimmune disease:
      rationale and initial clinical experience].
AB  - Mesenchymal stromal cells (MSC) are characterized by their proliferative
      capacity, their phenotype and their ability to multipotent differentiation.
      However, little is known about their function and characteristics in vivo. MSC
      posses a tropism for injured tissues. Numerous investigations of MSC in different
      model systems suggest an immunosuppressive potential, although the results are in
      part contradictory. Apparently, MSC exert these effects on nearly all cells in
      the immune system. However, the relevance and mechanisms of these phenomena in
      vivo are not clear. The clinical effectiveness of allogeneic MSC in the treatment
      of refractory graft-versus-host disease has raised hopes that MSC could offer a
      new concept for the therapy of other immune-mediated disorders. However, before
      MSC are introduced in clinical practise, several important questions as to their
      side effects have to be addressed. This includes the possibility that MSC may
      contribute to the induction of malignant diseases.

PMID- 19384553
TI  - [From stem cells to lymphocytes].
AB  - Two types of pluripotent stem cells form the origins of the cells of the innate
      and the adaptive immune system, as well as of essential elements of cooperating
      environments of this system. Pluripotent hematopoietic stem cells and their
      subordinated, sub-specialized progenitor cells develop, throughout life, the red
      cells, platelets, myeloid and lymphoid cells of this continuously regenerating
      cell system. Pluripotent mesenchymal cells generate, among other types of
      differentiated cells, chondrocytes, epithelial cells, adipocytes and osteoblasts.
      These osteoblasts not only produce bone, the primary location for the
      hematopoietic cell development, but also directly interact with the hematopoietic
      stem and progenitor cells - and also with the mature, antigen-experienced memory
      types of lymphocytes which return after successful fights with antigens to the
      place of their origin. These interactions occur both by cell-cell contacts and
      cytokine-cytokine receptor recognitions in so-called"niches", and induce and
      guide the developments of the hematopoietic cells. These early phases of
      hematopoietic development are antigen-independent, because the cells of the
      adaptive system, the lymphocytes, have not yet made antigen-specific receptors.
      As soon as these cells express T-cell and B-cell receptors for antigen they are
      subjected to negative and positive selection pressures, first by auto-antigens in
      the primary lymphoid organs, then after maturation and migration to secondary
      lymphoid organs, also to external, foreign antigens. The repertoires of these
      lymphocytes expressing TcR and BcR adapt to the body's own, as well as external
      environmental, antigens. While cell-cell contacts with cooperating non
      hematopoietic as well as hematopoietic cells, and cytokine-cytokine receptor
      interactions continue to induce the cellular responses resulting in
      proliferation, differentiation and/or programmed cell death (apoptosis) of the
      mature hematopoietic cells, such responses of lymphocytes are now dominated by
      the specific interactions of their antigen-specific receptors, TcRs or BrCs with
      antigens.

PMID- 19384555
TI  - Movement disorder and neuronal migration disorder due to ARFGEF2 mutation.
AB  - We report a child with a severe choreadystonic movement disorder, bilateral
      periventricular nodular heterotopia (BPNH), and secondary microcephaly based on
      compound heterozygosity for two new ARFGEF2 mutations (c.2031_2038dup and
      c.3798_3802del), changing the limited knowledge about the phenotype. The brain
      MRI shows bilateral hyperintensity of the putamen, BPNH, and generalized atrophy.
      Loss of ARFGEF2 function affects vesicle trafficking, proliferation/apoptosis,
      and neurotransmitter receptor function. This can explain BPNH and microcephaly.
      We hypothesize that the movement disorder and the preferential damage to the
      basal ganglia, specifically to the putamen, may be caused by an increased
      sensitivity to degeneration, a dynamic dysfunction due to neurotransmitter
      receptor mislocalization or a combination of both.

PMID- 19384557
TI  - Abstracts of the 16th Annual Congress of the European Society of Musculoskeletal
      Radiology (ESSR). Genoa, Italy. June 11-13, 2009.

PMID- 19384554
TI  - Genome-wide association studies in ADHD.
AB  - Attention-deficit/hyperactivity disorder, ADHD, is a common and highly heritable
      neuropsychiatric disorder that is seen in children and adults. Although
      heritability is estimated at around 76%, it has been hard to find genes
      underlying the disorder. ADHD is a multifactorial disorder, in which many genes,
      all with a small effect, are thought to cause the disorder in the presence of
      unfavorable environmental conditions. Whole genome linkage analyses have not yet
      lead to the identification of genes for ADHD, and results of candidate gene-based
      association studies have been able to explain only a tiny part of the genetic
      contribution to disease, either. A novel way of performing hypothesis-free
      analysis of the genome suitable for the identification of disease risk genes of
      considerably smaller effect is the genome-wide association study (GWAS). So far,
      five GWAS have been performed on the diagnosis of ADHD and related phenotypes.
      Four of these are based on a sample set of 958 parent-child trio's collected as
      part of the International Multicentre ADHD Genetics (IMAGE) study and genotyped
      with funds from the Genetic Association Information Network (GAIN). The other is
      a pooled GWAS including adult patients with ADHD and controls. None of the papers
      reports any associations that are formally genome-wide significant after
      correction for multiple testing. There is also very limited overlap between
      studies, apart from an association with CDH13, which is reported in three of the
      studies. Little evidence supports an important role for the 'classic' ADHD genes,
      with possible exceptions for SLC9A9, NOS1 and CNR1. There is extensive overlap
      with findings from other psychiatric disorders. Though not genome-wide
      significant, findings from the individual studies converge to paint an
      interesting picture: whereas little evidence-as yet-points to a direct
      involvement of neurotransmitters (at least the classic dopaminergic,
      noradrenergic and serotonergic pathways) or regulators of neurotransmission, some
      suggestions are found for involvement of 'new' neurotransmission and cell-cell
      communication systems. A potential involvement of potassium channel subunits and
      regulators warrants further investigation. More basic processes also seem
      involved in ADHD, like cell division, adhesion (especially via cadherin and
      integrin systems), neuronal migration, and neuronal plasticity, as well as
      related transcription, cell polarity and extracellular matrix regulation, and
      cytoskeletal remodeling processes. In conclusion, the GWAS performed so far in
      ADHD, though far from conclusive, provide a first glimpse at genes for the
      disorder. Many more (much larger studies) will be needed. For this, collaboration
      between researchers as well as standardized protocols for phenotyping and DNA
      collection will become increasingly important.

PMID- 19384559
TI  - Teaching feedback to first-year medical students: long-term skill retention and
      accuracy of student self-assessment.
AB  - BACKGROUND: Giving and receiving feedback are critical skills and should be
      taught early in the process of medical education, yet few studies discuss the
      effect of feedback curricula for first-year medical students. OBJECTIVES: To
      study short-term and long-term skills and attitudes of first-year medical
      students after a multidisciplinary feedback curriculum. DESIGN: Prospective pre-
      vs. post-course evaluation using mixed-methods data analysis. PARTICIPANTS: First
      year students at a public university medical school. INTERVENTIONS: We collected
      anonymous student feedback to faculty before, immediately after, and 8 months
      after the curriculum and classified comments by recommendation
      (reinforcing/corrective) and specificity (global/specific). Students also self
      rated their comfort with and quality of feedback. We assessed changes in comments
      (skills) and self-rated abilities (attitudes) across the three time points.
      MEASUREMENTS AND MAIN RESULTS: Across the three time points, students' evaluation
      contained more corrective specific comments per evaluation [pre-curriculum mean
      (SD) 0.48 (0.99); post-curriculum 1.20 (1.7); year-end 0.95 (1.5); p = 0.006].
      Students reported increased skill and comfort in giving and receiving feedback
      and at providing constructive feedback (p < 0.001). However, the number of
      specific comments on year-end evaluations declined [pre 3.35 (2.0); post 3.49
      (2.3); year-end 2.8 (2.1)]; p = 0.008], as did students' self-rated ability to
      give specific comments. CONCLUSION: Teaching feedback to early medical students
      resulted in improved skills of delivering corrective specific feedback and
      enhanced comfort with feedback. However, students' overall ability to deliver
      specific feedback decreased over time.

PMID- 19384560
TI  - Bone stress injuries are common in female military trainees: a preliminary study.
AB  - Although bone stress injuries are common in male military trainees, it is not
      known how common they are in female trainees. It also is unclear whether
      asymptomatic bone stress injuries heal if intensive training is continued. We
      prospectively followed 10 female trainees of a military Reserve Officer Course.
      The subjects underwent clinical and MRI examinations of the pelvis, thighs, and
      lower legs at the beginning, once during, and at the end of their 3-month course.
      We identified two to five injuries in every female trainee, all of whom already
      had the injuries at the beginning of the officer course. None of these injuries
      increased their severity despite vigorous training. Two-thirds were asymptomatic
      and low grade. Femoral and tibial shafts were the most common locations. Higher
      grade injuries were more likely symptomatic, but regardless of the MRI findings,
      female trainees expressed only mild to moderate symptoms. Asymptomatic, low-grade
      bone stress injuries of the femoral and tibial shaft are common in female
      recruits undergoing heavy physical training. Because these injuries seem to
      remain constant or even disappear despite continued heavy physical activity, we
      do not recommend routine screening of asymptomatic trainees. As some bone stress
      fractures may have severe consequences (eg, in the femoral neck), symptomatic
      bone stress injuries should be examined and treated.

PMID- 19384561
TI  - The Friedman-Eilber resection arthroplasty of the pelvis.
AB  - It has been argued that internal hemipelvectomy without reconstruction of the
      pelvic ring leads to poor ambulation and inferior patient acceptance. To
      determine the accuracy of this contention, we posed the following questions:
      First, how effectively does a typical patient ambulate following this procedure?
      Second, what is the typical functional capacity of a patient following internal
      hemipelvectomy? In the spring of 2006, we obtained video documentation of eight
      patients who had undergone resection arthroplasty of the hemipelvis seen in our
      clinic during routine clinical followup. The minimum followup in 2006 was 1.1
      years (mean, 8.2 years; range, 1.1-22.7 years); at the time of last followup in
      2008 the minimum followup was 2.9 years (mean, 9.8 years; range, 2.9-24.5 years).
      At last followup seven of the eight patients were without pain, and were able to
      walk without supports. The remaining patient used narcotic medication and a cane
      or crutch only occasionally. The mean MSTS score at the time of most recent
      followup was 73.3% of normal (range 53.3-80.0%; mean raw score was 22.0; range 16
      24). All eight patients ultimately returned to gainful employment. These
      observations demonstrate independent painless ambulation and acceptable function
      is possible following resection arthroplasty of the hemipelvis. LEVEL OF
      EVIDENCE: Level IV, case series. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19384562
TI  - Role of the extraosseus blood supply in osteoarthritic femoral heads?
AB  - Blood perfusion to the femoral head might be endangered during the surgical
      approach or the preparation of the femoral head or both in hip resurfacing
      arthroplasty. The contribution of the intramedullary blood supply to the femoral
      head in osteoarthritis is questionable. Therefore, the contribution of the
      extraosseous blood supply to osteoarthritic femoral heads was measured
      intraoperatively to question if there is measurable blood flow between the
      epiphysis and metaphysis in osteoarthritic hips in case of extraosseus vessel
      damage. At defined points during surgery we acquired the epiphyseal and
      metaphyseal femoral head perfusion by high-energy laser Doppler flowmetry.
      Complete femoral neck osteotomy sparing the retinacular vessels to simulate
      intraosseous blood disruption showed unchanged epiphyseal blood flow compared to
      initial measurement after capsulotomy. The pulsatile signal disappeared after
      transection of the retinacular vessels. Based on these acute measurements, we
      conclude intramedullary blood vessels to the femoral head do not provide
      measurable blood supply to the epiphysis once the medial femoral circumflex
      artery or the retinacular vessels have been damaged. We recommend the use of a
      safe surgical approach for hip resurfacing and careful implantation of the
      femoral component to respect blood supply to the femoral head and neck region in
      hip resurfacing arthroplasty.

PMID- 19384563
TI  - The depressive phenotype induced in adult female rats by adolescent exposure to
      THC is associated with cognitive impairment and altered neuroplasticity in the
      prefrontal cortex.
AB  - We recently demonstrated that Delta(9)-tetrahydrocannabinol (THC) chronic
      administration in female adolescent rats induces alterations in the emotional
      circuit ending in depressive-like behavior in adulthood. Since cognitive
      dysfunction is a major component of depression, we assessed in these animals at
      adulthood different forms of memory. Adolescent female rats were treated with THC
      or its vehicle from 35 to 45 post-natal days (PND) and left undisturbed until
      their adulthood (75 PND) when aversive and spatial memory was assessed using the
      passive avoidance and radial maze tasks. No alteration was found in aversive
      memory, but in the radial maze THC pre-treated animals exhibited a worse
      performance than vehicles, suggesting a deficit in spatial working memory. To
      correlate memory impairment to altered neuroplasticity, level of marker proteins
      was investigated in the hippocampus and prefrontal cortex, the most relevant
      areas for learning and memory. A significant decrease in synaptophysin and PSD95
      proteins was found in the prefrontal cortex of THC pre-treated rats, with no
      alterations in the hippocampus. Finally, proteomic analysis of the synapses in
      the prefrontal cortex revealed the presence of less active synapses characterized
      by reduced ability in maintaining normal synaptic efficiency. This picture
      demonstrates the presence of cognitive impairment in THC-induced depressive
      phenotype.

PMID- 19384564
TI  - 5-Hydroxyanthranilic acid, a tryptophan metabolite, generates oxidative stress
      and neuronal death via p38 activation in cultured cerebellar granule neurones.
AB  - The essential amino acid tryptophan is primarily metabolised through the
      kynurenine pathway, some components of which may be neurotoxic. We have now
      examined the potential toxicity of several kynurenine metabolites in relation to
      the generation of oxidative stress and activation of cell death signalling
      pathways in cultured cerebellar granule neurons. 3-Hydroxykynurenine (3HK), 3
      hydroxyanthranilic acid (3HAA) and 5-hydroxyanthranilic acid (5HAA) induced cell
      death which increased with exposure time and compound concentration. The
      neurotoxic effects of 3HK, 3HAA and 5HAA were prevented by catalase, but not by
      superoxide dismutase. In addition, Western blot analysis demonstrated p38
      activation due to 3HK or 5HAA treatment, although caspase-3 activation was not
      evident in either case. The results indicate that kynurenine metabolites can be
      neurotoxic via a caspase-3 independent mechanism, and that the minor metabolite
      5HAA is as potent a toxin as the better documented compounds 3HK and 3HAA.

PMID- 19384565
TI  - Behavioral perturbations after prenatal neurogenesis disturbance in female rat.
AB  - The exposure to methylazoxymethanol (MAM) at embryonic day 17 (E17) results in
      behavioral anomalies in male rats that mimic several features of schizophrenia,
      including their emergence after puberty. Given that both men and women are likely
      to develop this illness and that currently no animal model is validated for
      females, we examined the behavioral consequences of E17 MAM exposure in female
      rats. We compared E17 MAM- and saline-exposed female rats before and/or after
      puberty for spontaneous activity, alternance and spatial recognition (Y-maze),
      spatial learning (Morris water maze), and sensory gating using the prepulse
      inhibition task. MAM-exposed female rats exhibited a significant increase in
      spontaneous locomotor activity in a novel environment, compared to sham animals,
      which emerged only after puberty. They also had deficits in spontaneous
      alternation performance and spatial recognition in a Y-maze as well as reference
      memory deficits in a Morris water maze task. Lastly, MAM-exposed female rats
      spent significantly less time in social interaction at both pre- and post-puberty
      and had a deficit in prepulse inhibition of the startle reflex (PPI) at
      adulthood. In conclusion, the present results show that, in female rat, exposure
      to MAM at E17 results in a pattern of behavioral changes that, on the whole,
      mimic positive, negative, and cognitive dimensions of schizophrenia. E17 MAM
      exposure thus appears to be a valid model for schizophrenia in both males and
      females.

PMID- 19384566
TI  - Cyanidin-3-glucoside reverses ethanol-induced inhibition of neurite outgrowth:
      role of glycogen synthase kinase 3 Beta.
AB  - Ethanol is a potent teratogen for the developing central nervous system (CNS),
      and fetal alcohol syndrome (FAS) is the most common nonhereditary cause of mental
      retardation. Ethanol disrupts neuronal differentiation and maturation. It is
      important to identify agents that provide neuroprotection against ethanol
      neurotoxicity. Using an in vitro neuronal model, mouse Neuro2a (N2a)
      neuroblastoma cells, we demonstrated that ethanol inhibited neurite outgrowth and
      the expression of neurofilament (NF) proteins. Glycogen synthase kinase 3beta
      (GSK3beta), a multifunctional serine/threonine kinase negatively regulated
      neurite outgrowth of N2a cells; inhibiting GSK3beta activity by retinoic acid
      (RA) and lithium induced neurite outgrowth, while over-expression of a
      constitutively active S9A GSK3beta mutant prevented neurite outgrowth. Ethanol
      inhibited neurite outgrowth by activating GSK3beta through the dephosphorylation
      of GSK3beta at serine 9. Cyanidin-3-glucoside (C3G), a member of the anthocyanin
      family rich in many edible berries and other pigmented fruits, enhanced neurite
      outgrowth by promoting p-GSK3beta(Ser9). More importantly, C3G reversed ethanol
      mediated activation of GSK3beta and inhibition of neurite outgrowth as well as
      the expression of NF proteins. C3G also blocked ethanol-induced intracellular
      accumulation of reactive oxygen species (ROS). However, the antioxidant effect of
      C3G appeared minimally involved in its protection. Our study provides a potential
      avenue for preventing or ameliorating ethanol-induced damage to the developing
      CNS.

PMID- 19384567
TI  - Neuroprotective effect of ghrelin in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine mouse model of Parkinson's disease by blocking microglial
      activation.
AB  - Ghrelin is an endogenous ligand for growth hormone (GH) secretagogue receptor 1a
      (GHS-R1a) and is produced and released mainly from the stomach. It was recently
      demonstrated that ghrelin can function as a neuroprotective factor by inhibiting
      apoptotic pathways. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes
      nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest
      that activated microglia actively participate in the pathogenesis of Parkinson's
      disease (PD) neurodegeneration. However, the role of microglia in the
      neuroprotective properties of ghrelin is still unknown. Here we show that, in the
      mouse MPTP PD model generated by an acute regimen of MPTP administration,
      systemic administration of ghrelin significantly attenuates the loss of
      substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic
      fibers through the activation of GHS-R1a. We also found that ghrelin reduced
      nitrotyrosine levels and improved the impairment of rota-rod performance. Ghrelin
      prevents MPTP-induced microglial activation in the SNpc and striatum, the
      expression of pro-inflammatory molecules tumor necrosis factor alpha (TNF-alpha)
      and interleukin-1beta (IL-1beta), and the activation of inducible nitric oxide
      synthase. The inhibitory effect of ghrelin on the activation of microglia appears
      to be indirect by suppressing matrix metalloproteinase-3 (MMP-3) expression in
      stressed dopaminergic neurons because GHS-R1a is not expressed in SNpc microglial
      cells. Finally, in vitro administration of ghrelin prevented 1-methyl-4
      phenylpyridinium-induced dopaminergic cell loss, MMP-3 expression, microglial
      activation, and the subsequent release of TNF-alpha, IL-1beta, and nitrite in
      mesencephalic cultures. Our data indicate that ghrelin may act as a survival
      factor for dopaminergic neurons by functioning as a microglia-deactivating factor
      and suggest that ghrelin may be a valuable therapeutic agent for
      neurodegenerative diseases such as PD.

PMID- 19384568
TI  - Neuronal and glial alterations due to focal cortical hypoxia induced by direct
      cobalt chloride (CoCl2) brain injection.
AB  - Ischemic brain injury is a dynamic process that involves oxidative stress,
      inflammation, and cell death, as well as activation of endogenous adaptive and
      regenerative mechanisms depending on activation of transcription factors such as
      hypoxia inducible factor 1-alpha (HIF-1alpha). Because CoCl2 activates HIF
      1alpha, we described a new focal-hypoxia model by direct intracerebral CoCl2
      injection. Adult male Wistar rats were intracerebrally injected with CoCl2 (2
      microl-50 mM), in frontoparietal cortex of right hemisphere, and saline (2
      microl) in the contralateral hemisphere. In slides of fixed brains at 1, 6, 9, 24
      h or 5 day after treatment, TTC, histochemistry (toluidine blue, Hoescht-33342,
      TUNEL), immunostaining (HIF-1alpha, GFAP), Lycopersicon esculentum lectin
      staining, and electron microscopy (EM) were performed. Immediately after 1 h post
      CoCl2 injection, HIF-1alpha stabilization and neuronal nuclear shrinkage and
      cromathin condensation were observed by immunostaining and EM, respectively.
      Neuronal apoptotic nuclear morphology and GFAP immunoreactivity and lectin
      maximal reactivity were detected during 6-9 h. Ultrastructural alterations of
      morphology included edematous perinuclear cytoplasm, organelles and endoplasmic
      reticulum (RE) enlargement, mitochondrial swelling with increased matrix density,
      and deposits of electron-dense material. Neurons showed particular nuclear
      indentations. Astrocytes and oligodendrocytes presented alterations in both
      nuclei and RE with dilated lumen and altered mitochondrias, and all these
      ultrastructural changes became detectable at day 5. CoCl2 cortical injection
      mimics focal brain ischemia, inducing neuronal death and glial activation. This
      model brings the opportunity to develop focal ischemia in selected brain areas to
      study their functional consequences and potential pharmacological therapies for
      in vivo models of stroke.

PMID- 19384569
TI  - Nicotine induces sensitization of turning behavior in 6-hydroxydopamine lesioned
      rats.
AB  - Nicotinic drugs have been proposed as putative drugs to treat Parkinson's disease
      (PD). In this study, we investigated whether nicotine can sensitize parkinsonian
      animals to the effect of dopaminergic drugs. Testing this hypothesis is important
      because nicotine has been shown to present neuroprotective and acute symptomatic
      effects on PD, but few studies have addressed the question of whether it may
      induce long-lasting effects on dopamine neurotransmission. We tested this
      hypothesis in the 6-hydroxydopamine (6-OHDA) rat model of PD. A pretreatment of
      these rats with 0.1-1.0 mg/kg nicotine induced a dose-dependent sensitization of
      the turning behavior when the animals were challenged with the dopamine receptor
      agonist apomorphine 24 h later. In agreement with previous studies, while
      apomorphine induced contraversive turns, nicotine, as well as amphetamine,
      induced ipsiversive turns in the 6-OHDA rats. This result suggests that, like
      amphetamine, nicotine induces turning behavior by promoting release of dopamine
      in the non-lesioned striatum of the rats. However, it is unlikely that the
      release of dopamine may also explain the nicotine-induced sensitization of
      turning behavior. First, the dopamine amount that could be released in the
      lesioned hemi-striatum by the nicotine pretreatment was minimum-less than 3%, as
      detected by HPLC-EC. Second, a pretreatment with amphetamine did not induce this
      behavioral sensitization. A pretreatment with apomorphine-induced sensitization,
      but it was minimal when compared to that induced by nicotine. Therefore, it is
      unlikely that the sensitization of the turning behavior induced by nicotine was
      consequent of the release of dopamine. However, the expression of such
      sensitization seems to depend on the activation of dopaminergic receptors, since
      it was seen when the nicotine-sensitized animals were challenged with
      apomorphine, but not with a second nicotine challenge. These findings are
      relevant for PD drug therapy since they suggest that the doses of dopaminergic
      drugs used to treat PD could be reduced if a nicotinic drug were co-administered.

PMID- 19384570
TI  - Non-hypoxic stabilization of hypoxia-inducible factor alpha (HIF-alpha):
      relevance in neural progenitor/stem cells.
AB  - Hypoxia-inducible factor-1 (HIF-1) plays an important role in neural progenitor
      cell (NPC) propagation and dopaminergic differentiation. In the presence of
      oxygen and iron, hypoxia-inducible factor 1 alpha (HIF-1alpha) is rapidly
      degraded via the prolyl hydroxylase (PHD)/VHL pathway. In addition to hypoxia,
      various non-hypoxic stimuli can stabilize HIF-1alpha in NPCs and influence the
      transcription of HIF-regulated genes. Here, we investigate various hypoxia
      mimetics: deferoxamine (DFO), ciclopirox olamine (CPX), dimethyloxallyl glycine
      (DMOG), a novel HIF-PHD inhibitor (FG-4497) and cobalt chloride (CoCl(2)) with
      respect to their ability to enhance in vitro proliferation, neurogenesis and
      dopaminergic differentiation of human fetal mesencephalic NPCs (hmNPCs) in
      ambient oxygen (21%). Although able to stabilize HIF-1alpha, iron chelators (DFO
      and CPX) and DMOG were toxic to hmNPCs. CoCl(2) was beneficial only towards
      neuronal and dopaminergic differentiation, while FG-4497 enhanced proliferation,
      neurogenesis and dopaminergic differentiation of hmNPCs. Both CoCl(2) and FG-4497
      were protective to human dopaminergic neurons. Finally, exposure to hyperbaric
      oxygen (HBO) also stabilized HIF-1alpha in hmNPCs and induced neurogenesis in
      vitro. These findings suggest that several HIF stabilizing agents or conditions
      can rescue impaired neurons and promote neurogenesis in vitro.

PMID- 19384571
TI  - Metallothionein treatment attenuates microglial activation and expression of
      neurotoxic quinolinic acid following traumatic brain injury.
AB  - The kynurenine pathway has been implicated as a major component of the
      neuroinflammatory response to brain injury and neurodegeneration. We found that
      the neurotoxic kynurenine pathway intermediate quinolinic acid (QUIN) is rapidly
      expressed, within 24 h, by reactive microglia following traumatic injury to the
      rodent neocortex. Furthermore, administration of the astrocytic protein
      metallothionein attenuated this neuroinflammatory response by reducing microglial
      activation (by approximately 30%) and QUIN expression. The suppressive effect of
      MT was confirmed upon cultured cortical microglia, with 1 mug/ml MT almost
      completely blocking interferon-gamma induced activation of microglia and QUIN
      expression. These results demonstrate the neuroimmunomodulatory properties of MT,
      which may have therapeutic applications for the treatment of traumatic brain
      injury.

PMID- 19384572
TI  - Modulation of behavior by expected reward magnitude depends on dopamine in the
      dorsomedial striatum.
AB  - Reward-predictive cues are important to guide behavioral responding. In a series
      of experiments, we sought to characterize the role of dopamine in the dorsomedial
      striatum in modulation of reward-directed responding by visual cues. Different
      groups of rats subjected to infusion of 6-hydroxydopamine or vehicle into the
      posterior part of the dorsomedial striatum (pDMS) were tested in three
      experiments. In experiment 1, rats were examined in an operant task demanding a
      lever release response. In intact rats, reaction times of responding were
      reliably shorter on cued large reward trials than on cued small reward trials.
      Results showed that pDMS dopamine depletion impaired reward-dependent modulation
      of reaction times, if visual cues predict large versus small reward, but not if
      visual cues predict reward versus no reward. These observations suggest that
      dopamine signaling in the pDMS contributes to a process through which reward
      directed responses become guided by cues associated with distinct reward
      magnitudes. Experiment 2 revealed that pDMS dopamine depletion did not compromise
      the acquisition of a conditional visual discrimination task in an operant box
      that required learning a rule of the type "if the cue light is bright press left
      lever for reward, if dim press right lever". Furthermore, experiment 3 showed
      that pDMS dopamine depletion did not impair the acquisition of a cross maze task
      that required learning a visual cue discrimination strategy to obtain food
      reward. Together results of experiments 2 and 3 indicate that dopamine signaling
      in the pDMS does not subserve stimulus discrimination per se and stimulus
      response learning.

PMID- 19384574
TI  - Unconjugated TAT carrier peptide protects against excitotoxicity.
AB  - We report in this article for the first time the neuroprotective effects of
      unconjugated TAT carrier peptide against a mild excitotoxic stimulus both in
      vitro and in vivo. In view of the widespread use of TAT peptides to deliver
      neuroprotectants into cells, it is important to know the effects of the carrier
      itself. Unconjugated TAT carrier protects dissociated cortical neurons against
      NMDA but not against kainate, suggesting that TAT peptides may interfere with
      NMDA signaling. Furthermore, a retro-inverso form of the carrier peptide caused a
      reduction in lesion volume (by about 50%) in a rat neonatal cerebral ischemia
      model. Thus, even though TAT is designed merely as a carrier, its own
      pharmacological activity will need to be considered in the analysis of TAT-linked
      neuroprotectant peptides.

PMID- 19384573
TI  - Assessment of symptomatic and neuroprotective efficacy of Mucuna pruriens seed
      extract in rodent model of Parkinson's disease.
AB  - Mucuna pruriens (MP) has long been used in Indian traditional medicine as support
      in the treatment of Parkinson's disease. However, no systematic preclinical
      studies that aimed at evaluating the efficacy of this substance are available to
      date. This study undertook an extensive evaluation of the antiparkinsonian
      effects of an extract of MP seeds known to contain, among other components, 12.5%
      L: -dihydroxyphenylalanine (L: -DOPA), as compared to equivalent doses of L: 
      DOPA. Moreover, the neuroprotective efficacy of MP and its potential rewarding
      effects were evaluated. The results obtained reveal how an acute administration
      of MP extract at a dose of 16 mg/kg (containing 2 mg/kg of L: -DOPA) consistently
      antagonized the deficit in latency of step initiation and adjusting step induced
      by a unilateral 6-hydroxydopamine lesion, whereas L: -DOPA was equally effective
      only at the doses of 6 mg/kg. At the same dosage, MP significantly improved the
      placement of the forelimb in vibrissae-evoked forelimb placing, suggesting a
      significant antagonistic activity on both motor and sensory-motor deficits. The
      effects of MP extract were moreover investigated by means of the turning behavior
      test and in the induction of abnormal involuntary movements (AIMs) after either
      acute or subchronic administration. MP extract acutely induced a significantly
      higher contralateral turning behavior than L: -DOPA (6 mg/kg) when administered
      at a dose of 48 mg/kg containing 6 mg/kg of L: -DOPA. On subchronic
      administration, both MP extract (48 mg/kg) and L: -DOPA (6 mg/kg) induced
      sensitization of contralateral turning behavior; however, L: -DOPA alone induced
      a concomitant sensitization in AIMs suggesting that the dyskinetic potential of
      MP is lower than that of L: -DOPA. MP (48 mg/kg) was also effective in
      antagonizing tremulous jaw movements induced by tacrine, a validated test
      reproducing parkinsonian tremor. Furthermore, MP induced no compartment
      preference in the place preference test, indicating the lack of components
      characterized by rewarding effects in the extract. Finally, in a subchronic mice
      model of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine hydrochloride (MPTP)
      induced dopamine neuron degeneration, MP extract did not prove capable of
      preventing either tyrosine hydroxylase decrease induced by MPTP or astroglial or
      microglial activation as assessed by means of GFAP and CD11b
      immunohistochemistry, supporting the absence of neuroprotective effects by MP.
      Characterization MP extract strongly supports its antiparkinsonian activity.

PMID- 19384575
TI  - Chronic dietary administration of valproic acid protects neurons of the rat
      nucleus basalis magnocellularis from ibotenic acid neurotoxicity.
AB  - Valproic acid (VPA) has been used for many years as a drug of choice for epilepsy
      and mood disorders. Recently, evidence has been proposed for a wide spectrum of
      actions of this drug, including antitumoral and neuroprotective properties.
      Valproic acid-mediated neuroprotection in vivo has been so far demonstrated in a
      limited number of experimental models. In this study, we have tested the
      neuroprotective potential of chronic (4 + 1 weeks) dietary administration of VPA
      on degeneration of cholinergic and GABAergic neurons of the rat nucleus basalis
      magnocellularis (NBM), injected with the excitotoxin, ibotenic acid (IBO), an
      animal models that is relevant for Alzheimer's disease-like neurodegeneration. We
      show that VPA treatment significantly protects both cholinergic and GABAergic
      neurons present in the injected area from the excitotoxic insult. A significant
      level of neuroprotection, in particular, is exerted towards the cholinergic
      neurons of the NBM projecting to the cortex, as demonstrated by the substantially
      higher levels of cholinergic markers maintained in the target cortical area of
      VPA-treated rats after IBO injection in the NBM. We further show that chronic VPA
      administration results in increased acetylation of histone H3 in brain,
      consistent with the histone deacetylase inhibitory action of VPA and putatively
      linked to a neuroprotective action of the drug mediated at the epigenetic level.

PMID- 19384576
TI  - Low doses of carbon monoxide protect against experimental focal brain ischemia.
AB  - Carbon monoxide (CO) is associated with central nervous system toxicity. However,
      evidence also indicates that CO can be protective, depending on its
      concentration. To determine if CO can be neuroprotective after ischemic brain
      injury, we subjected mice to transient middle cerebral artery occlusion and
      exposed them to different concentrations of CO. We found that in mice, low CO
      levels protected the brain from injury following 90-min transient focal ischemia
      and 48 h of reperfusion. When inhalation of 125 or 250 ppm CO began immediately
      at the onset of reperfusion, total hemispheric infarct volume was reduced by 32.1
      +/- 8.9% and 62.2 +/- 14.4%, respectively; with an extended therapeutic window of
      1-3 h after ischemia, CO inhalation also attenuated infarct volume significantly.
      Furthermore, early CO exposure limited brain edema formation by 3.2 +/- 0.8% (125
      ppm) and 2.6 +/- 0.3% (250 ppm). Finally, CO inhalation significantly improved
      neurological deficit scores at 48 h of survival time after ischemia. Transient
      elevation of carboxyhemoglobin levels returned rapidly to baseline when CO
      exposure was stopped. These findings suggest a potential application of CO to
      treat brain ischemic stroke.

PMID- 19384577
TI  - Dual modulation of ERK1/2 and p38 MAP kinase activities induced by minocycline
      reverses the neurotoxic effects of the prion protein fragment 90-231.
AB  - Several in vitro and in vivo studies addressed the identification of molecular
      determinants of the neuronal death induced by PrP(Sc) or related peptides. We
      developed an experimental model to assess PrP(Sc) neurotoxicity using a
      recombinant polypeptide encompassing amino acids 90-231 of human PrP (hPrP90-231)
      that corresponds to the protease-resistant core of PrP(Sc) identified in prion
      infected brains. By means of mild thermal denaturation, we can convert hPrP90-231
      from a PrP(C)-like conformation into a PrP(Sc)-like structure. In virtue of these
      structural changes, hPrP90-231 powerfully affected the survival of SH-SY5Y cells,
      inducing caspase 3 and p38-dependent apoptosis, while in the native alpha-helix
      rich conformation, hPrP90-231 did not induce cell toxicity. The aim of this study
      was to identify drugs able to block hPrP90-231 neurotoxic effects, focusing on
      minocycline, a tetracycline with known neuroprotective activity. hPrP90-231
      caused a caspase 3-dependent apoptosis via the blockade of ERK1/2 activation and
      the subsequent activation of p38 MAP kinase. We propose that hPrP90-231-induced
      apoptosis is dependent on the inhibition of ERK1/2 responsiveness to neurotrophic
      factors, removing a tonic inhibition of p38 activity and resulting in caspase 3
      activation. Minocycline prevented hPrP90-231-induced toxicity interfering with
      this mechanism: the pretreatment with this tetracycline restored ERK1/2 activity
      and reverted p38 and caspase 3 activities. The effects of minocycline were not
      mediated by the prevention of hPrP90-231 structural changes or cell
      internalization (differently from Congo Red). In conclusion, minocycline elicits
      anti-apoptotic effects against the neurotoxic activity of hPrP90-231 and these
      effects are mediated by opposite modulation of ERK1/2 and p38 MAP kinase
      activities.

PMID- 19384578
TI  - Effect of adenosine A(2A) receptor antagonists on L-DOPA-induced hydroxyl radical
      formation in rat striatum.
AB  - A(2A) adenosine receptor antagonists have been proposed as a new therapy for
      Parkinson's disease (PD). Since oxidative stress plays an important role in the
      pathogenesis of PD, we studied the effect of the selective A(2A) adenosine
      receptor antagonists 8-(3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2
      furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) on
      L: -3,4-dihydroxyphenylalanine (L: -DOPA)-induced hydroxyl radical generation
      using in vivo microdialysis in the striatum of freely moving rats. L: -DOPA (100
      mg/kg; in the presence of benserazide, 50 mg/kg) given acutely or repeatedly for
      14 days generated a high level of hydroxyl radicals, measured by HPLC with
      electrochemical detection, as the product of their reaction with p-hydroxybenzoic
      acid (PBA). CSC (1 mg/kg) and ZM 241385 (3 mg/kg) decreased haloperidol (0.5
      mg/kg)-induced catalepsy, while at low doses of 0.1 and 0.3 mg/kg, respectively,
      they did not display an effect. CSC (1 and 5 mg/kg) and ZM 241385 (3 and 9 mg/kg)
      given acutely, or CSC (1 mg/kg) and ZM 241385 (3 mg/kg) given repeatedly,
      increased the production of hydroxyl radicals in dialysates from rat striatum.
      Both acute and repeated administration of CSC (0.1 and 1 mg/kg) and ZM 241385 (3
      mg/kg) decreased L: -DOPA-induced generation of hydroxyl radicals. However, a
      high single dose of either CSC (5 mg/kg) and ZM 241385 (9 mg/kg) markedly
      potentiated the effect of L: -DOPA on hydroxyl radical production. The increase
      in hydroxyl radical production by acute and chronic injection of CSC and ZM
      241385 may be related to the increased release of dopamine (DA) and its
      metabolism in striatal dialysates. Similarly, increased DA release following a
      single high dose of CSC or ZM 241385 appears to be responsible for augmentation
      of L: -DOPA-induced hydroxyl radical formation. Conversely, the inhibition of L: 
      DOPA-induced production of hydroxyl radical by single and repeated low doses of
      CSC or repeated low doses of ZM 241385 may be related to reduced DA metabolism.
      Summing up, A(2A) antagonists, used as a supplement of L: -DOPA therapy,
      depending on the dose used, may have a beneficial or adverse effect on ongoing
      neurodegenerative processes and accompanying oxidative stress.

PMID- 19384579
TI  - A chronic iron-deficient/high-manganese diet in rodents results in increased
      brain oxidative stress and behavioral deficits in the morris water maze.
AB  - Iron deficiency (ID) is especially common in pregnant women and may even persist
      following childbirth. This is of concern in light of reports demonstrating that
      ID may be sufficient to produce homeostatic dysregulation of other metals,
      including manganese (Mn). These results are particularly important considering
      the potential introduction of the Mn-containing gas additive, methyl
      cyclopentadienyl manganese tricarbonyl (MMT), in various countries around the
      world. In order to model this potentially vulnerable population, we fed female
      rats fed either control (35 mg Fe/kg chow; 10 mg Mn/kg chow) or low iron/high
      manganese (IDMn; 3.5 mg Fe/kg chow; 100 mg Mn/kg chow) diet, and examined whether
      these changes had any long-term behavioral effects on the animals' spatial
      abilities, as tested by the Morris water maze (MWM). We also analyzed behavioral
      performance on auditory sensorimotor gating utilizing prepulse inhibition (PPI),
      which may be related to overall cognitive performance. Furthermore, brain and
      blood metal levels were assessed, as well as regional brain isoprostane
      production. We found that treated animals were slightly ID, with statistically
      significant increases in both iron (Fe) and Mn in the hippocampus, but
      statistically significantly less Fe in the cerebellum. Additionally, isoprostane
      levels, markers of oxidative stress, were increased in the brain stem of IDMn
      animals. Although treated animals were indistinguishable from controls in the PPI
      experiments, they performed less well than controls in the MWM. Taken together,
      our data suggest that vulnerable ID populations exposed to high levels of Mn may
      indeed be at risk of potentially dangerous alterations in brain metal levels
      which could also lead to behavioral deficits.

PMID- 19384580
TI  - Effect of chronic and subchronic organic solvents exposure on balance control of
      workers in plant manufacturing adhesive materials.
AB  - High-level occupational exposure to volatile organic solvents may elicit
      neurotoxic effects, especially on central and peripheral structures involved in
      balance ability. Studies on balance control in relation with exposure levels
      close to the threshold limit values are scarce. This study aimed to assess the
      neurotoxic effects of chronic and subchronic exposure to organic solvents among
      workers in plant manufacturing adhesive materials. Balance control was evaluated
      in 18 subjects, mainly exposed to n-hexane and toluene, with current median
      exposure levels of 222 and 102 mg/m(3), respectively, and a median exposure
      duration of 21 years, and in 32 nonexposed controls, using posturography tests
      with and without sensory conflicting situations. Tests were undergone at the
      beginning of the work shift (chronic exposure) following a week end, and after 72
      h (subchronic exposure). Balance control performance was lower in chronically
      exposed workers compared to controls, and got worse after subchronic exposure,
      particularly during situations, where vestibular information was important. Our
      study suggests that a low-level and prolonged exposure to volatile organic
      solvents, mainly n-hexane and toluene, in the workplace is associated with
      deleterious central effects involved in postural regulation. This neurotoxicity
      is characterized by difficulties to use the most relevant information to control
      balance, leading to altered management of sensory conflicting situations.

PMID- 19384581
TI  - Ocular manifestations of crystal methamphetamine use.
AB  - Numerous medical sequelae associated with illicit drug use have been reported.
      Nevertheless, there has been scarce documentation of the effects of these drugs
      on the eyes. Drug-induced ocular symptoms include decreased visual acuity,
      disturbances in perception, and even flashbacks. Methamphetamine (METH) is a
      highly addictive drug whose abuse has spread worldwide during the past two
      decades. METH abuse is associated with many adverse psychiatric and medical
      consequences including strokes and psychosis. METH-induced ophthalmic
      complications are rarely discussed but include retinal vasculitis, episcleritis,
      panophthalmitis, endophthalmitis, scleritis, retinopathy, corneal ulceration, and
      transient visual losses. Because the drug has shown a marked increase in the
      prevalence of its use amongst pregnant women, there has also been an increase of
      drug-induced complications in fetuses and newborn babies. These complications
      need to be further detailed and studied. Herein, the authors report on the ocular
      complications associated with METH abuse. They also discuss some potential
      mechanisms for the toxic effects of the drug on that system.

PMID- 19384583
TI  - Consumption of grape seed extract prevents amyloid-beta deposition and attenuates
      inflammation in brain of an Alzheimer's disease mouse.
AB  - Polyphenols extracted from grape seeds are able to inhibit amyloid-beta (Abeta)
      aggregation, reduce Abeta production and protect against Abeta neurotoxicity in
      vitro. We aimed to investigate the therapeutic effects of a polyphenol-rich grape
      seed extract (GSE) in Alzheimer's disease (AD) mice. APP(Swe)/PS1dE9 transgenic
      mice were fed with normal AIN-93G diet (control diet), AIN-93G diet with 0.07%
      curcumin or diet with 2% GSE beginning at 3 months of age for 9 months. Total
      phenolic content of GSE was 592.5 mg/g dry weight, including gallic acid (49
      mg/g), catechin (41 mg/g), epicatechin (66 mg/g) and proanthocyanidins (436.6 mg
      catechin equivalents/g). Long-term feeding of GSE diet was well tolerated without
      fatality, behavioural abnormality, changes in food consumption, body weight or
      liver function. The Abeta levels in the brain and serum of the mice fed with GSE
      were reduced by 33% and 44%, respectively, compared with the Alzheimer's mice fed
      with the control diet. Amyloid plaques and microgliosis in the brain of
      Alzheimer's mice fed with GSE were also reduced by 49% and 70%, respectively.
      Curcumin also significantly reduced brain Abeta burden and microglia activation.
      Conclusively, polyphenol-rich GSE prevents the Abeta deposition and attenuates
      the inflammation in the brain of a transgenic mouse model, and this thus is
      promising in delaying development of AD.

PMID- 19384584
TI  - 1-Benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous parkinsonism-inducing
      toxin, strongly potentiates MAO-dependent dopamine oxidation and impairs dopamine
      release: ex vivo and in vivo neurochemical studies.
AB  - 1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), an endogenous neurotoxin, is
      known to cause a parkinsonism-like syndrome in rodents and primates. In this
      study we evaluated the effects of single and multiple 1BnTIQ (50 mg/kg i.p.)
      administration on the concentrations of dopamine, serotonin, and respective
      metabolites (homovanillic acid, HVA; 3,4-dihydroxyphenylacetic acid, DOPAC; 3
      methoxytyramine, 3-MT; and 5-hydroxyindolacetic acid, 5-HIAA), in substantia
      nigra, striatum (STR), and nucleus accumbens of Wistar rats. In addition, the
      effect of 1BnTIQ on locomotor activity and dopamine release in vivo was also
      estimated in rat STR. In a behavioral study, acute administration of 1BnTIQ (50
      mg/kg i.p.) produced a significant decrease in exploratory locomotor activity. A
      high-performance liquid chromatography with electrochemical detection ex vivo
      study showed that a single injection of 1BnTIQ produced a dramatic fall in the
      dopamine concentration in the noted brain regions (approximately 65%; P < 0.01),
      but not in striatal serotonin. Moreover, 1BnTIQ reduced the content of the
      extraneuronal dopamine metabolite 3-MT by 70% (P < 0.01). Conversely, levels of
      DOPAC, HVA, and 5-HIAA were elevated by 220, 320, and 185%, respectively (P <
      0.01). Interestingly, multiple 1BnTIQ treatments (50 mg/kg/day i.p. x 10 days)
      resulted in development of tolerance to its dopamine depressing effect, while the
      impairment of dopamine synthesis was persisted. An in vivo microdialysis study
      demonstrated that 1BnTIQ (50 mg/kg i.p.) produced a profound and long-lasting
      decrease in extraneuronal striatal dopamine. Concurrently, however, DOPAC and HVA
      were elevated. This comparison between ex vivo and in vivo effects of 1BnTIQ
      provides greater insight into the neurotoxic actions of 1BnTIQ specific to
      dopamine neurons. 1BnTIQ neurotoxicity may be related to an impairment of
      dopamine storage, leading to a fall in intraneuronal dopamine and enhanced
      dopamine catabolism through a monoamine oxidize-dependent oxidative pathway that
      results in free radical production and ultimate cell death. Because 1BnTIQ is an
      endogenous compound, it may be one of the factors responsible for idiopathic
      Parkinson's disease.

PMID- 19384585
TI  - Protective effect of memantine against Doxorubicin toxicity in primary neuronal
      cell cultures: influence a development stage.
AB  - One of the serious unwanted effects of the anthracycline anticancer drug
      doxorubicin (Dox, adriamycin) is its neurotoxicity, which can be evoked by the
      activation of extracellular (FAS/CD95/Apo-1) pathway of apoptosis in cells. Since
      memantine, a clinically used N-methyl-D: -aspartic acid (NMDA) receptor
      antagonist, shows antiapoptotic action in several models of neuronal cell damage,
      in this study we evaluated the effect of memantine on the cell death induced by
      Dox in primary neuronal cell cultures. First, we investigated the effect of
      different concentrations of Dox (0.1-5 microM) on mouse neocortical, hippocampal,
      striatal, and cerebellar neurons on 7- and 12-day in vitro (DIV). The 7 DIV
      neuronal cell cultures were more prone to Dox-induced cell death than 12 DIV
      cultures. The cerebellar neurons were the most resistant to Dox-induced apoptosis
      in comparison to neuronal cell cultures derived from the forebrain. Memantine
      (0.1-2 microM) attenuated the Dox-evoked lactate dehydrogenase release in 7 DIV
      neuronal cell cultures with no significant effect on 12 DIV cultures. The
      ameliorating effect of memantine on Dox-mediated cell death was also confirmed by
      an increase in cell viability measured by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide reduction assay. There was no effect of memantine on
      Dox-induced caspase-8 and -3 activity and Dox-evoked decrease in mitochondrial
      potential, although attenuation in the number of cells with apoptotic DNA
      fragmentation was observed. We also showed that the antiapoptotic effect of
      memantine in our model was NMDA receptor-independent, since two other antagonists
      of this receptor, MK-801 and AP-5, did not attenuate Dox-induced cell death.
      Furthermore, memantine did not influence the Dox-evoked increase in cytoplasmic
      Ca2+ level. The obtained data suggest developmental regulation of both, the Dox
      mediated neurotoxicity and efficacy of memantine in alleviating the Dox-induced
      cell damage in neuronal cell cultures. Moreover, this neuroprotective effect of
      memantine seems not to be dependent on caspase-3 activity and on the antagonistic
      action on NMDA receptor.

PMID- 19384586
TI  - Molecular determinants of multiple effects of nickel on NMDA receptor channels.
AB  - Nickel (Ni2+) is a toxic metal that affects the function of several neuronal
      ionic channels. Ni2+ inhibits N-methyl-D: -aspartate receptor (NR) channel in a
      voltage-dependent manner, but also causes enhancement of NR2B-containing channel
      activity and voltage-independent inhibition of those containing NR2A. The present
      work was aimed to find the sites of Ni2+ interaction on the NR2A and NR2B
      subunits by expressing wild-type and mutated NRs in either HEK293 cells or
      Xenopus laevis oocytes. The point mutation N616G in the pore region of the NR2B
      subunit completely removed the voltage-dependent block. In NR2 subunits deleted
      for their entire amino terminal domain (ATD) and expressed with wild-type NR1
      subunit, voltage-independent inhibition of NR2A-containing channels was not
      modified, but the potentiation effect was abolished in NR2B-containing channels.
      In the latter channels, potentiation of the current was also removed by H127A,
      D101A, D104A point mutations and by the double mutation H127AD101A, all located
      in lobe I of ATD, and reduced by the point mutation T233A in lobe II, suggesting
      that the interaction site that causes potentiation shares common determinants
      with the Zn2+ and ifenprodil binding sites. In contrast, in NR2A-containing
      channels, we postulate the existence of an additional divalent cation binding
      site in the M3-M4 extracellular loop. In these channels, the point mutation H801A
      in the NR2A subunit caused an important reduction of the voltage-independent
      block, with a 7-time increase in IC(50). The block was also partially, but not as
      prominently, reduced by the double mutation H705AH709A in the same region of NR1.
      This additional binding site can be responsible of specific heavy metal
      interaction with NR channels.

PMID- 19384587
TI  - Substance P upregulates LTB4 in rat adherent macrophages from granuloma induced
      by KMnO4.
AB  - Substance P (SP) is an important neuropeptide involved in neurogenic inflammation
      and most of its pathophysiological functions are mediated through binding to the
      neurokinin-1 receptor. SP exerts various proinflammatory actions on immune-cells,
      including macrophages. Several compounds such as cytokines have the capacity to
      activate and stimulate macrophages to produce arachidonic acid oxygenation and
      lipoxygenation products. Leukotriene B4 (LTB4) is one of the most important
      mediators of leukocyte activation in acute and chronic inflammatory reactions.
      LTB4 stimulates chemotaxis, lysosomal enzyme release, and cell aggregation. In
      this report, we studied the effect of SP on rat adherent granuloma macrophages
      (RAGMs). The chronic granuloma in rat was induced by dorsal injections of a
      potassium permanganate (KMnO4) saturated crystal solution (200 microl of a 1:40
      dilution). After 7 days, all rats developed a subcutaneous granuloma in the
      injection site from which infiltrated macrophages were extracted, isolated, and
      cultured in vitro. We tested the hypothesis that SP stimulates the production of
      LTB4 in RAGMs and increases lipoxygenase expression. Here we show that the cell
      free supernatant of RAGMs stimulated with SP (10 microM), resulted in
      statistically significant increases of LTB4 Preincubation of RAGMs with NDGA
      (nordihydroguaiaretic acid (10 microM), completely abolished the production of
      LTB(4) in the supernatants and lipoxygenase expression on RAGMs challenged with
      SP, or the cation ionophore A23187 (positive control). Similar effects were
      obtained when the cells were pretreated with dexamethasone (10 microM). Our
      results suggest that SP is able to stimulate the release of LTB4 and lipoxygenase
      expression in macrophages from chronic inflammatory granuloma and provide further
      evidence for a neuroinflammatory pathway.

PMID- 19384588
TI  - Disubstituted diaryl diselenides inhibit [3H]-serotonin uptake in rats.
AB  - Diphenyl diselenide (PhSe)2, the parent compound of disubstituted diaryl
      diselenides, produces significant antidepressant-like effect when evaluated in
      the forced swimming test (FST) in rats. The goal of this study was to investigate
      the effects of diphenyl diselenide (PhSe)2, m-trifluoromethyl-diphenyl diselenide
      (F3CPhSe)2 and p-methoxy-diphenyl diselenide (CH3OPhSe)2 on [3H]-serotonin uptake
      in rat platelets and synaptosomes. At concentrations higher than 10 microM
      (PhSe)2, and (F3CPhSe)2 inhibited about 20% [3H]-serotonin uptake in platelets.
      (CH3OPhSe)2 inhibited [3H]-serotonin uptake in platelets at concentrations higher
      than 1 microM. Similarly, (PhSe)2, (F3CPhSe)2, and (CH3OPhSe)2 significantly
      inhibited [3H]-serotonin uptake (about 50%) in synaptosomes from rat brain at
      concentrations higher than 1 microM. The maximal inhibitory effects of (PhSe)2,
      (F3CPhSe)2, and (CH3OPhSe)2 on [3H]-serotonin uptake from rat synaptosomes were
      65%, 96%, and 80%, respectively. In conclusion, our results demonstrate that
      disubstituted diaryl diselenides altered monoaminergic system by interacting with
      monoamine uptake.

PMID- 19384589
TI  - PGF(2alpha) FP receptor contributes to brain damage following transient focal
      brain ischemia.
AB  - Although some of the COX-2 metabolites and prostaglandins have been implicated in
      stroke and excitotoxicity, the role of prostaglandin F(2alpha) (PGF(2alpha)) and
      its FP receptor have not been elucidated in the pathogenesis of ischemic
      reperfusion (I/R) brain injury. Here we investigated the FP receptor's
      contribution in a unilateral middle cerebral artery (MCA) occlusion model of
      focal cerebral ischemia in mice. The MCA in wild type (WT) and FP knockout (FP(-/
      )) C57BL/6 male mice was transiently occluded with a monofilament for 90 min.
      After 96 h of reperfusion, the FP(-/-) mice had 25.3% less neurological deficit
      (P < 0.05) and 34.4% smaller infarct volumes (P < 0.05) than those of the WT
      mice. In a separate cohort, physiological parameters were monitored before,
      during, and after ischemia, and the results revealed no differences between the
      groups. Because excitotoxicity is an acute mediator of stroke outcome, the effect
      of acute NMDA-induced neurotoxicity was also tested. Forty-eight hours after
      unilateral intrastriatal NMDA injection, excitotoxic brain damage was 20.8% less
      extensive in the FP(-/-) mice (P < 0.05) than in the WT counterparts, further
      supporting the toxic contribution of the FP receptor in I/R injury. Additionally,
      we investigated the effect of post-treatment with the FP agonist latanoprost in
      mice subjected to MCA occlusion; such treatment resulted in an increase in
      neurological deficit and infarct size in WT mice (P < 0.05), though no effects
      were observed in the latanoprost-treated FP(-/-) mice. Together, the results
      suggest that the PGF(2alpha) FP receptor significantly enhances cerebral ischemic
      and excitotoxic brain injury and that these results are of importance when
      planning for potential development of therapeutic drugs to treat stroke and its
      acute and/or long term consequences.

PMID- 19384590
TI  - Diabetic hyperglycemia aggravates seizures and status epilepticus-induced
      hippocampal damage.
AB  - Epileptic seizures in diabetic hyperglycemia (DH) are not uncommon. This study
      aimed to determine the acute behavioral, pathological, and electrophysiological
      effects of status epilepticus (SE) on diabetic animals. Adult male Sprague-Dawley
      rats were first divided into groups with and without streptozotocin (STZ)-induced
      diabetes, and then into treatment groups given a normal saline (NS) (STZ-only and
      NS-only) or a lithium-pilocarpine injection to induce status epilepticus (STZ +
      SE and NS + SE). Seizure susceptibility, severity, and mortality were evaluated.
      Serial Morris water maze test and hippocampal histopathology results were
      examined before and 24 h after SE. Tetanic stimulation-induced long-term
      potentiation (LTP) in a hippocampal slice was recorded in a multi-electrode dish
      system. We also used a simulation model to evaluate intracellular adenosine
      triphosphate (ATP) and neuroexcitability. The STZ + SE group had a significantly
      higher percentage of severe seizures and SE-related death and worse learning and
      memory performances than the other three groups 24 h after SE. The STZ + SE
      group, and then the NS + SE group, showed the most severe neuronal loss and mossy
      fiber sprouting in the hippocampal CA3 area. In addition, LTP was markedly
      attenuated in the STZ + SE group, and then the NS + SE group. In the simulation,
      increased intracellular ATP concentration promoted action potential firing. This
      finding that rats with DH had more brain damage after SE than rats without
      diabetes suggests the importance of intensively treating hyperglycemia and
      seizures in diabetic patients with epilepsy.

PMID- 19384591
TI  - The mitochondrial ATP-sensitive potassium channel blocker 5-hydroxydecanoate
      inhibits toxicity of 6-hydroxydopamine on dopaminergic neurons.
AB  - The neurotoxin 6-hydroxydopamine is commonly used in models of Parkinson's
      disease, and a potential factor in the pathogenesis of the disease. However, the
      mechanisms responsible for 6-hydroxydopamine-induced dopaminergic degeneration
      have not been totally clarified. Reactive oxygen species (ROS) derived from 6
      OHDA uptake and intraneuronal autooxidation, extracellular 6-OHDA autooxidation,
      and microglial activation have been involved. The mitochondrial implication is
      controversial. Mitochondrial ATP-sensitive K (mitoK(ATP)) channels may provide a
      convergent target that could integrate these different mechanisms. We observed
      that in primary mesencephalic cultures and neuron-enriched cultures, treatment
      with the mitoK(ATP) channel blocker 5-hydroxydecanoate, inhibits the dopaminergic
      degeneration induced by low doses of 6-OHDA. Furthermore, 5-hydroxydecanoate
      blocks the 6-OHDA-induced decrease in mitochondrial inner membrane potential and
      inhibits 6-OHDA-induced generation of superoxide-derived ROS in dopaminergic
      neurons. The results suggest that low doses of 6-OHDA may generate low levels of
      ROS through several mechanisms, which may be insufficient to induce neuron death.
      However, they could act as a trigger to activate mitoK(ATP) channels, thereby
      enhancing ROS production and the subsequent dopaminergic degeneration.
      Furthermore, the present study provides additional data for considering
      mitoK(ATP) channels as a potential target for neuroprotection.

PMID- 19384592
TI  - P2X7 nucleotide receptor is coupled to GSK-3 inhibition and neuroprotection in
      cerebellar granule neurons.
AB  - In this study we report the coupling of nucleotide receptors to GSK-3 signalling,
      a relevant survival pathway in cerebellar granule neurons. P2X(7) agonist BzATP
      induced a 3-4-fold increase in GSK-3 phosphorylation, which is reported to be
      associated with the catalytic activity inhibition. This effect was dependent on
      extracellular calcium and PKC, and independent of PI3-K (phosphatidyl-inositol-3
      kinase)/Akt, the main survival route of neurotrophins. BzATP also prevented the
      apoptosis of granule neurons induced by the pharmacological inhibition of the PI3
      K signalling. Both effects, BzATP-mediated GSK-3 phosphorylation and
      neuroprotection, were abolished by P2X(7) receptor antagonists, BBG, PPADS and A
      438079. We found that BzATP prevented the progressive GSK-3 dephosphorylation and
      caspase-3 activation occurring under conditions of sustained PI3-K inhibition.
      These results reveal that P2X(7) receptor activation could provide a relevant
      survival route alternative to classical neurotrophic factors.

PMID- 19384593
TI  - Potential of choroid plexus epithelial cell grafts for neuroprotection in
      Huntington's disease: what remains before considering clinical trials.
AB  - The choroid plexuses (CPs) help maintain the extracellular milieu of the brain by
      modulating chemical exchange between the cerebrospinal fluid and brain
      parenchyma, surveying the chemical and immunological status of the brain,
      detoxifying the brain, secreting a nutritive "cocktail" of polypeptides, and
      participating in repair processes following trauma. Based on recent pre-clinical
      studies in animal models, a novel therapeutic approach has been suggested that
      involves transplanting CP for treating acute and chronic brain diseases. To date
      most studies have focused on rodent and primate models of Huntington's disease
      (HD) with demonstrations that transplants of CP can prevent the behavioral and
      anatomical consequences of striatal degeneration. Despite the encouraging results
      that lend support to the possibility of protecting vulnerable neurons in HD,
      critical basic science issues remain unexamined that limit the translation of the
      pre-clinical findings into clinical evaluations of CP transplants for HD. Here we
      briefly outline the logic behind using this novel cell source for
      transplantation, the pre-clinical data supporting this concept, and most
      importantly identify several critical, gating issues that remain prior to moving
      this approach forward in a meaningful clinical manner.

PMID- 19384594
TI  - Neonatal fluoxetine exposure affects the neuronal structure in the somatosensory
      cortex and somatosensory-related behaviors in adolescent rats.
AB  - Selective serotonin reuptake inhibitor (SSRI)-type antidepressants are often
      prescribed to depressive pregnant women for their less adverse side effects.
      However, growing evidences have shown increased congenital malformations and poor
      neonatal adaptation in the perinatal SSRI-exposed human infants as well as animal
      pups. In this study, we examined the effects of early exposure of fluoxetine, the
      most popular SSRI-type antidepressant, on the developing somatosensory system.
      Physiological saline or fluoxetine (10 mg/kg) was subcutaneously injected into
      neonatal rats from P0 to P6. Somatosensory-related behaviors were examined in
      adolescence (P30-P35). Morphological features of the primary somatosensory cortex
      were checked at P7 and P35. The tactile and thermal perceptions as well as
      locomotor activity were affected by neonatal fluoxetine treatment. At the
      morphological level, the number of branch tips of thalamocortical afferents to
      the somatosensory cortex was reduced in the fluoxetine-treated rats. Furthermore,
      the spiny stellate neurons in the layer IV somatosensory cortex had reduced
      dendritic span and complexity with fewer branches, shorter dendritic length, and
      smaller dendritic field. The spine density of spiny stellate neurons was
      significantly reduced whereas the spine length of mushroom- and branched-type was
      increased. Taken together, these results indicate that neonatal fluoxetine
      administration has long-lasting effects on the function and structure in the
      somatosensory system. Sensory information processing may be disturbed in the
      neonatal fluoxetine-treated animals due to the structural deformation in the
      thalamocortical afferents and dendritic structures of the spiny stellate neurons
      in the layer IV somatosensory cortex.

PMID- 19384595
TI  - Fifteen-year experience in treating blepharospasm with Botox or Dysport: same
      toxin, two drugs.
AB  - OBJECTIVES: To compare the clinical characteristics and the long-term outcome of
      a large series of patients with blepharospasm (BS) treated with the two most used
      brands of BoNT-A over the last 15 years. METHODS: We have reviewed the clinical
      charts of 128 patients with BS who received botulinum neurotoxin (BoNT) in 1341
      treatments (Botox in 1009, Dysport in 332) over the last 15 years. RESULTS: Mean
      dose per session was 34U +/- 15 for Botox and 152U +/- 54 for Dysport. Mean
      latency of clinical effect was 4.5 +/- 4.6 days for Botox and 5.0 +/- 5.7 days
      for Dysport (P > 0.05). Mean duration of clinical improvement was higher for
      Dysport than Botox: 80.1 +/- 36.3 and 66.2 +/- 39.8 days, respectively (P <
      0.01). In a six-point scale (0: no efficacy, 6: remission of BS), the mean
      efficacy of both treatments was 3.60 +/- 1.3; 3.51 +/- 1.4 (Botox) and 3.85 +/-
      1.2 (Dysport), P < 0.01. The doses of Botox (beta = 0.40) and Dysport (beta =
      0.16) were significantly increased over time. Side effects occurred in 325 out of
      1341 treatments (24.2%): 21.8% of the patients who had received Botox, and in
      31.6% of those who had received Dysport (P < 0.01). CONCLUSIONS: Both brands are
      effective and safe in treating blepharospasm; efficacy is long lasting. The
      differences in outcome and side effects suggest that, albeit the active drug is
      the same, Botox and Dysport should be considered as two different drugs.

PMID- 19384596
TI  - Methamphetamine induces long-term alterations in reactivity to environmental
      stimuli: correlation with dopaminergic and serotonergic toxicity.
AB  - Methamphetamine (METH) abuse is known to induce persistent cognitive and
      behavioral abnormalities, in association with alterations in serotonin (5-HT) and
      dopamine (DA) systems, yet the neurobiological mechanisms underpinning this link
      are elusive. Thus, in the present study we analyzed the long-term impact of an
      acute toxic regimen of METH (4 mg/kg, subcutaneous x 4 injections, 2 h apart) on
      the reactivity of adult male rats to environmental stimuli, and correlated it to
      toxicity on 5-HT and DA innervations. Two separate groups of METH-injected rats
      were compared to their saline-treated controls on object exploration and startle
      paradigms, at either 1 or 3 weeks after METH administration, respectively. Twenty
      four hours after behavioral testing, animals were sacrificed, and the neurotoxic
      effects of the METH schedule on DA and 5-HT terminals were measured through
      immunochemical quantification of their transporters (DAT and 5-HTT). At both 1
      and 3 weeks after treatment, METH-injected rats exhibited a significant decline
      in the number of exploratory approaches to unfamiliar objects, which was
      significantly correlated with a parallel reduction in DAT immunoreactivity (IR)
      in the nucleus accumbens (NAc) core. Furthermore, METH-treated rats displayed a
      significant enhancement in startle magnitude after 3 (but not 1) weeks, which was
      inversely correlated with a decrement in 5-HTT IR in the Cg3 infralimbic area of
      prefrontal cortex. Our results suggest that METH induces long-term changes in
      object exploration and startle responsiveness, which may be respectively
      underpinned by reductions in DAergic and 5-HTergic brain terminals.

PMID- 19384597
TI  - Histaminergic activity in a rodent model of Parkinson's disease.
AB  - Rats lesioned shortly after birth with 6-OHDA have been proposed to be a near
      ideal model of severe Parkinson's disease, because of non-lethality of the
      procedure, near-total destruction of nigrostriatal dopaminergic fibers, and near
      total dopamine (DA) denervation of striatum. There are scarce data that in
      Parkinson's disease, activity of the central histaminergic system is increased.
      Therefore, the aim of this study was to determine histamine content in the brain
      and the effect of histamine receptor antagonists on behavior of adult rats. At 3
      days after birth, Wistar rats were pretreated with desipramine (20.0 mg/kg ip) 1
      h before bilateral icv administration of the catecholaminergic neurotoxin 6-OHDA
      (67 microg base, on each side) or saline-ascorbic acid (0.1%) vehicle (control).
      At 8 weeks levels of DA and its metabolites L: -3,4-dihydroxyphenylalanine
      (DOPAC) and homovanillic acid (HVA) were estimated in the striatum and frontal
      cortex by HPCL/ED technique. In the hypothalamus, hippocampus, frontal cortex,
      and medulla oblongata, the level of histamine was analyzed by immunoenzymatic
      method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped
      activity) were additionally made on control and 6-OHDA neonatally lesioned rats.
      Effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor
      antagonists (e.g., S(+)chlorpheniramine, H(1); cimetidine, H(2); thioperamide,
      H(3) agonist) were determined. We confirmed that 6-OHDA significantly reduced
      contents of DA and its metabolites in the brain in adulthood. Histamine content
      was significantly increased in the hypothalamus, hipocampus, and medulla
      oblongata. Moreover, in 6-OHDA-lesioned rats behavioral response was altered
      mainly by thioperamide (H(3) antagonist). These findings indicate that histamine
      and the central histaminergic system are altered in the brain of rats lesioned to
      model Parkinson's disease, and that histaminergic neurons exert a modulating role
      in Parkinsonian 6-OHDA-lesioned rats.

PMID- 19384598
TI  - Methamphetamine preconditioning: differential protective effects on monoaminergic
      systems in the rat brain.
AB  - Pretreatment with methamphetamine (METH) can attenuate toxicity due to acute METH
      challenges. The majority of previous reports have focused mainly on the effects
      of the drug on the striatal dopaminergic system. In the present study, we used a
      regimen that involves gradual increases in METH administration to rats in order
      to mimic progressively larger doses of the drug used by some human METH addicts.
      We found that this METH preconditioning was associated with complete protection
      against dopamine depletion caused by a METH challenge (5 mg/kg x 6 injections
      given 1 h apart) in the striatum and cortex. In contrast, there was no
      preconditioning-mediated protection against METH-induced serotonin depletion in
      the striatum and hippocampus, with some protection being observed in the cortex.
      There was also no protection against METH-induced norepinephrine (NE) depletion
      in the hippocampus. These results indicate that, in contrast to the present
      dogmas, there might be differences in the mechanisms involved in METH toxicity on
      monoaminergic systems in the rodent brain. Thus, chronic injections of METH might
      activate programs that protect against dopamine toxicity without influencing drug
      induced pathological changes in serotoninergic systems. Further studies will need
      to evaluate the cellular and molecular bases for these differential responses.

PMID- 19384599
TI  - Methylene blue provides behavioral and metabolic neuroprotection against optic
      neuropathy.
AB  - Methylene blue (MB) is a diaminophenothiazine with potent antioxidant and unique
      redox properties that prevent morphologic degenerative changes in the mouse
      retina induced by rotenone, a specific mitochondrial complex I inhibitor. This
      study evaluated pigmented rats to determine whether MB's neuroprotective effects
      against rotenone-mediated retinal neurotoxicity have functional relevance and
      whether these effects are mediated by an improvement in neuronal energy
      metabolism in vivo. Visual function was behaviorally assessed by determining
      differences in the illuminance sensitivity threshold pre- and post-bilateral
      intravitreal injection of rotenone (200 microg/kg) or rotenone plus MB (70
      microg/kg). Retinal degeneration was morphologically studied using unbiased
      stereological tools. Changes in histochemically determined cytochrome oxidase
      activity in the visual pathway were used to evaluate the impact of treatments on
      neuronal energy metabolism. Rotenone induced a 1.4 log unit increase in the
      illumination threshold compared to baseline, as well as a 32% decrease in
      ganglion cell layer cell (GCL) density, and a 56% decrease in GCL layer + nerve
      fiber layer thickness. Co-administration of MB prevented the changes in visual
      function and the retinal histopathology. Furthermore, rotenone induced a
      functional deafferentation of the visual system, as revealed by decreases in the
      metabolic activity of the retina, superior colliculus, and visual cortex. These
      metabolic changes were also prevented by MB. The results provided the first
      demonstration of MB's behavioral and metabolic neuroprotection against optic
      neuropathy, and implicate MB as a candidate neuroprotective agent with metabolic
      enhancing properties that may be used in the treatment of neurodegenerative
      diseases associated with mitochondrial dysfunction.

PMID- 19384600
TI  - Small-molecule mediated neuroprotection in an in situ model of tauopathy.
AB  - Small-molecule inhibitors of neurofibrillary lesion formation may have utility
      for treatment of Alzheimer's disease and certain forms of frontotemporal lobar
      degeneration. These lesions are composed largely of tau protein, which aggregates
      to form intracellular fibrils in affected neurons. Previously it was shown that
      chronic overexpression of human tau protein within identified neurons (anterior
      bulbar cells) of the sea lamprey induced a phenotype-resembling tauopathic
      neurodegeneration, including the formation of tau filaments, fragmentation of
      dendritic arbors, and eventual cell death. Development of this neurodegenerative
      phenotype was blocked by chronic administration of a benzothiazole derivative
      termed N3 ((E)-2-[[4-(dimethylamino)phenyl]azo]-6-methoxybenzothiazole) to
      lamprey aquaria. Here we examined the mechanism of action of N3 and an alkene
      analog termed N4 ((E)-2-[2-[4-(dimethylamino)phenyl]ethenyl]-6
      methoxybenzothiazole) in vitro and in the lamprey model. Results showed that
      although both compounds entered the lamprey central nervous system, only N3
      arrested tauopathy. On the basis of in vitro aggregation assays, neither compound
      was capable of directly inhibiting tau filament formation. However, N3, but not
      N4, was capable of partially antagonizing the binding of Thioflavin S to
      synthetic tau filaments. The results suggest that occupancy of N3-binding sites
      on nascent tau filaments may significantly retard the progressive degeneration
      accompanying tau overexpression in lamprey.

PMID- 19384601
TI  - Comparative neuroprotective effects of rasagiline and aminoindan with selegiline
      on dexamethasone-induced brain cell apoptosis.
AB  - Stress can affect the brain and lead to depression; however, the molecular
      pathogenesis is unclear. An association between stress and stress-induced
      hypersecretion of glucocorticoids occurs during stress. Dexamethasone (a
      synthetic glucocorticoid steroid) has been reported to induce apoptosis and
      increase the activity of monoamine oxidase (MAO) (Youdim et al. 1989). MAO is an
      enzyme for the degradation of aminergic neurotransmitters; dopamine,
      noradrenaline and serotonin and dietary amines and MAO inhibitors are classical
      antidepressant drugs. In this study, we have compared the ability of rasagiline
      (Azilect) and its main metabolite, R-aminoindan with selegiline (Deprenyl) in
      prevention of dexamethasone-induced brain cell death employing human
      neuroblastoma SH-SY5Y cells and glioblastoma 1242-MG cells. Dexamethasone reduced
      cell viability as measured by MTT test, but rasagiline, selegiline, and 1-R
      aminoindan could significantly prevent dexamethasone-induced brain cell death.
      Among three drugs, rasagiline had the highest neuroprotective effect.
      Furthermore, the inhibitory effects of these drugs on MAO B catalytic activity
      and on apoptotic DNA damage (TUNEL staining) were examined. Rasagiline exhibited
      highest inhibition on MAO B enzymatic activity and prevention on DNA damage as
      compared to selegiline and 1-R-aminoindan. In summary, the greater
      neuroprotective effect of rasagiline may be associated with the combination of
      the parent drug and its metabolite 1-R-aminoindan.

PMID- 19384602
TI  - Audiovisual non-verbal dynamic faces elicit converging fMRI and ERP responses.
AB  - In an everyday social interaction we automatically integrate another's facial
      movements and vocalizations, be they linguistic or otherwise. This requires
      audiovisual integration of a continual barrage of sensory input-a phenomenon
      previously well-studied with human audiovisual speech, but not with non-verbal
      vocalizations. Using both fMRI and ERPs, we assessed neural activity to viewing
      and listening to an animated female face producing non-verbal, human
      vocalizations (i.e. coughing, sneezing) under audio-only (AUD), visual-only (VIS)
      and audiovisual (AV) stimulus conditions, alternating with Rest (R).
      Underadditive effects occurred in regions dominant for sensory processing, which
      showed AV activation greater than the dominant modality alone. Right posterior
      temporal and parietal regions showed an AV maximum in which AV activation was
      greater than either modality alone, but not greater than the sum of the
      unisensory conditions. Other frontal and parietal regions showed Common
      activation in which AV activation was the same as one or both unisensory
      conditions. ERP data showed an early superadditive effect (AV > AUD + VIS, no
      rest), mid-range underadditive effects for auditory N140 and face-sensitive N170,
      and late AV maximum and common-activation effects. Based on convergence between
      fMRI and ERP data, we propose a mechanism where a multisensory stimulus may be
      signaled or facilitated as early as 60 ms and facilitated in sensory-specific
      regions by increasing processing speed (at N170) and efficiency (decreasing
      amplitude in auditory and face-sensitive cortical activation and ERPs). Finally,
      higher-order processes are also altered, but in a more complex fashion.

PMID- 19384603
TI  - Critical roles of voltage-dependent sodium channels in the process of
      synaptogenesis during the postnatal cortical development of rats.
AB  - The developmental changes of the sodium channel and construction of synapse
      connection were studied in cerebral cortical pyramidal neurons of rats at
      different age groups. We used whole-cell patch-clamp recordings to characterize
      electrophysiological properties of cortical neurons at different age stages,
      including the sodium currents, APs evoked by depolarizing current and short-term
      plasticity of the eEPSCs. The result shows that the sodium currents undergo a
      hyperpolarizing shift in activation process and acceleration of activation and
      inactivation with age. The maximal sodium current also increased with maturation,
      and the evident difference appeared from P7-P11 (with the day of birth as P0) to
      P12-P15 group. The tendency of the sodium current density changes which exhibited
      the same properties as that of sodium current, showed the significant increases
      from P19-P21 to P >or= 22 group. The APs' parameters exhibited the age-dependent
      changes except the threshold, including the increase of the peak amplitude from P
      <or= 6 to P16-P18 groups, and the curtailment of duration and the time-to-peak
      with age. The amplitude of 1st eEPSC increased with maturation, and STP displays
      depression at all observed groups. In addition, although STP also exhibited
      depression in response to last three stimulations in P >or= 22 group, the 2nd
      response showed the tendency of facilitation compared with the younger age
      groups. Our results indicated that the cerebral cortical pyramidal neurons of
      rats are undergoing marked changes in the characteristics of their sodium
      channels with maturation, which play a critical role in synaptogenesis and
      construction of the neuronal network.

PMID- 19384604
TI  - Parent-child acculturation patterns and substance use among Hispanic adolescents:
      a longitudinal analysis.
AB  - Acculturation discrepancy theory predicts that conflicting cultural preferences
      between adolescents and their parents will increase the adolescents' risk for
      behavior problems such as substance use. This study evaluated this hypothesis in
      a sample of 1683 Hispanic students in Southern California who completed surveys
      in 9th and 10th grade. Measures included the students' own cultural orientations
      and their perceptions of their parents' preference for their cultural
      orientations ("Perceived Parental Cultural Expectations"--PPCE). Hispanic PPCE in
      9th grade was a risk factor for lifetime, but not past-month, cigarette, alcohol,
      and marijuana use in 10th grade. The adolescents' own Hispanic orientation in 9th
      grade was protective against lifetime and past-month smoking and marijuana use
      and lifetime alcohol use in 10th grade. The effects of the acculturation
      variables did not vary according to generation in the U.S. Change in
      acculturation between 9th and 10th grade was statistically significant but small
      in magnitude. Increases in parent-child Hispanic acculturation discrepancy (i.e.,
      the difference between the adolescents' own cultural orientations and their PPCE,
      with adolescents perceiving that their parents wanted them to be more Hispanic
      oriented than they actually were) from 9th to 10th grade were associated with an
      increased risk of substance use. Family-based interventions for acculturating
      Hispanic families may be useful in decreasing the likelihood of substance use
      among Hispanic adolescents.

PMID- 19384605
TI  - The challenge of transplants to an intersubjectively established sense of
      personal identity.
AB  - Face transplants have been performed, in a small number, since 2005. Popular
      concern over the morality of the face transplant has tended to focus on the role
      that one's face plays in one's sense of self or one's personal identity. In order
      to address this concern, the current paper will explore the significance of face
      transplants in the light of a theory of the self that draws on symbolic
      interactionism, narrative theory, and accounts of embodiment. The paper will
      respond to certain presuppositions concerning personal identity made by Huxtable
      and Woodley. A theory of the self will be articulated that draws on the work of
      Merleau-Ponty and G. H. Mead, in order to place embodiment and social interaction
      centrally to an understanding of self-identity. This will allow an account of the
      nature of the suffering that a face transplant seeks to remedy, and its worth as
      an operation, and crucially the impact that it may have on the sense of personal
      identity of the recipient of the transplant. The conclusion will review the
      treatment in the context of the prejudices that members of contemporary societies
      may hold against those with disfigurements.

PMID- 19384606
TI  - The effectiveness of distal soft tissue procedures in hallux valgus.
AB  - BACKGROUND: Hallux valgus is a common disorder affecting mostly women population.
      Distal soft tissue procedure in the treatment of hallux valgus is one of the main
      operative techniques described. The aim of this study is to evaluate the outcomes
      of McBride's distal soft tissue procedure in hallux valgus cases. MATERIALS AND
      METHODS: This study includes 30 patients (27 women) having 31 hallux valgus, who
      were treated between 1999 and 2004. Modified McBride's distal soft tissue
      procedure was carried out in all cases. Pain status of the cases was recorded by
      using VAS, clinical assessment described by Bonney and Macnab, and American
      Orthopaedic Foot and Ankle Society's (AOFAS) score at the last follow up.
      RESULTS: The mean hallux valgus and intermetatarsal angles decreased from 31.4
      degrees and 13.8 degrees to 13.5 degrees and 10.5 degrees , respectively, with an
      average follow-up period of 54.4 months. AOFAS's score displayed significant
      improvement from 57 to 87. The mean VAS showed a significant decrease from 8.75
      preoperatively to 2.1 at the last follow-up. According to Bonney and Macnab
      criteria, only one case was accepted as poor result due to 5 degrees hallux
      varus. CONCLUSIONS: McBride's distal soft tissue procedure yields high rate of
      satisfaction for mild to moderate hallux valgus with no bony complications
      related to osteotomy.

PMID- 19384607
TI  - Clinical and radiological midterm results from using the Fixion expandable
      intramedullary nail in transverse and short oblique fractures of femur and tibia.
AB  - BACKGROUND: A locked nail is the principal method used to eliminate rotatory
      components in femoral and tibial fractures. Nevertheless, weight bearing is not
      directed onto the fracture site, slowing down the healing process; another
      possibility is to use a large-diameter nail and ream the canal to obtain as much
      adherence as possible and increase the grip, but this can cause a number of
      complications. The expandable nail is a new option that in theory should remove
      some problems with previous techniques. MATERIALS AND METHODS: This was a
      retrospective nonrandomized study encompassing 21 femoral fractures and 27 tibial
      fractures in 45 patients. They were classified according to the AO
      classification. Clinical and radiological checks were done at one, three, and six
      months and at one year from the surgery in order to check for signs of clinical
      and radiological healing. A good alignment was considered to be the presence of a
      deformity of less than 5 degrees in the sagittal and lateral planes and the
      absence of rotatory clinically evident problems. This protocol was adhered to up
      to six months after surgery by all of the patients, while only 62.2% performed
      the last control. The mean follow-up was 15 months. A second group of 48
      consecutive fractures (24 femural and 24 tibial) treated with locked nail was
      created to compare surgical times. RESULTS: Appropriate alignment was observed in
      all cases; the healing process appeared slower: radiological healing occurred in
      most cases at six months. The following complications were reported: a case of
      intraoperative fracture widening with no effect on the treatment; a case of a
      lesion of the tip of the nail with pneumatic system rupture that necessitated
      nail substitution; two cases of retarded consolidation at six months, with both
      tibial fractures treated successfully by intralesion platelet gel; a case of
      incarcerated nail on 17 removals, resolved by shearing. We had no cases of
      clinically evident compartment syndrome or pulmonary embolism. CONCLUSIONS: The
      expandable Fixion nail presents significant advantages in the treatment of
      transverse and short oblique fractures of femur and tibia because it is easy to
      use, involves minimal X-ray exposure and can control rotations. Nevertheless, it
      high cost limits its use. We consider it as an alternative to locked nail.

PMID- 19384608
TI  - Expandable intramedullary nailing and platelet rich plasma to treat long bone non
      unions.
AB  - BACKGROUND: Roentgenographic and functional outcomes of expandable self locking
      intramedullary nailing and platelet rich plasma (PRP) gel in the treatment of
      long bone non-unions are reported. MATERIALS AND METHODS: Twenty-two patients
      suffering from atrophic diaphyseal long bone non-unions were enrolled in the
      study. Patients were treated with removal of pre-existing hardware, decortication
      of non-union fragments, and fixation of pseudoarthrosis with expandable
      intramedullary nailing (Fixion, Disc'O Tech, Tel Aviv, Israel). At surgery, PRP
      was placed in the pseudoarthrosis rim. RESULTS: The thirteen-month follow-up
      showed 91% (20/22 patients) of patients attaining bony union. The average time to
      union was 21.5 weeks. No infection, neurovascular complication, rotational
      malalignment, or limb shortening >4 mm were observed. The healing rate of non
      unions was comparable to that observed in previous studies but with a lower
      complication frequency. CONCLUSIONS: The combined use of self locking
      intramedullary nailing and PRP in the management of atrophic diaphyseal long bone
      non-unions seems to produce comparable results with less complications than
      previously reported. Further data are warranted to investigate the single
      contribution of PRP gel and Fixion nail.

PMID- 19384609
TI  - Internal fixation of proximal humeral fractures with a Polarus humeral nail.
AB  - BACKGROUND: Proximal humeral fractures occur frequently. Displaced or unstable
      fractures require open reduction and internal fixation. Our objective was to
      investigate the clinical and radiographic results of the internal fixation using
      Polarus humeral nails for fractures of the proximal humerus. MATERIALS AND
      METHODS: From January 2001 to April 2006, 54 shoulders of 54 patients (44
      females, 10 males) underwent the intramedullary fixation using Polarus humeral
      nail. Mean age of the patients was 66-year-old (39-89) at the time of the
      surgery. Fracture-type by Neer classification was 2-part (29 shoulders), 3-part
      (22 shoulders) and 4-part (3 shoulders). The clinical and radiological outcomes
      were evaluated. RESULTS: All the shoulders after osteosynthesis obtained bone
      union. There was no osteonecrosis of the humeral head. Functional outcome
      measured by JOA score averaged 81 points. Totally 43 patients (79%) had
      satisfactory to excellent results. Varus deformity was seen in 4 shoulders (8%)
      and the deformity of the greater tuberosity in 4 (8%). CONCLUSION: The Polarus
      intramedullary humeral nail is effective for the treatment of proximal humeral
      fractures.

PMID- 19384610
TI  - Ipsilateral femoral neck and shaft fractures: a retrospective analysis of two
      treatment methods.
AB  - BACKGROUND: No consensus exists regarding the optimal treatment of ipsilateral
      femoral neck and shaft fractures. The three major issues related to these
      fractures are the optimal timing of surgery, which fracture to stabilize first,
      and the optimal implant to use. In an effort to find answers to these three key
      issues, we report our experience of managing 27 patients with ipsilateral femoral
      neck and shaft fractures by using two different treatment methods, i.e.,
      reconstruction-type intramedullary nailing and various plate combinations.
      MATERIALS AND METHODS: We divided patients into two groups. Group I included 15
      patients (13 males and 2 females) who were operated with cancellous lag screws or
      dynamic hip screws (DHS) for fractured neck and compression plate fixation for
      fractured shaft of the femur. Group II included 12 patients (11 males and 1
      female) who were operated with reconstruction-type intramedullary nailing.
      RESULTS: Mean age was 33.2 and 37.9 years in group I and II, respectively. Mean
      delay in surgery was 5.9 and 5.4 days in group I and II, respectively. Average
      union time for femoral neck fracture in groups I and II were 15.2 and 17.1 weeks,
      respectively; and for shaft fracture these times were 20.3 and 22.8 weeks,
      respectively. There were 13 (86.6%) good, 1 (6.7%) fair and 1 (6.7%) poor
      functional results in group I. There were 10 (83.3%) good, 1 (8.3%) fair and 1
      (8.3%) poor functional results in group II. CONCLUSIONS: Both of the treatment
      methods used in the present study achieved satisfactory functional outcome in
      these complex fractures. Fixation with plate for shaft and screws or DHS for hip
      is easy from a technical point of view. Choice of the treatment method should be
      dictated primarily by the type of femoral neck fracture and the surgeon's
      familiarity with the treatment method chosen. The femoral neck fracture should
      preferably be stabilized first, and a delay of 5-6 days does not affect the
      ultimate functional outcome.

PMID- 19384611
TI  - Internal fixation of proximal humeral fractures with locking proximal humeral
      plate (LPHP) in elderly patients with osteoporosis.
AB  - BACKGROUND: Different operative techniques used for treating displaced proximal
      humeral fractures could result in malunion, non-union, osteonecrosis of humeral
      head, loosening of screw and loss of reduction particularly in comminuted and
      osteoporotic fractures. Locking compression plate (LPHP) has been proposed for
      open reduction and internal fixation of these fractures and is associated with
      less complication rate. MATERIALS AND METHODS: We prospectively assessed the
      functional outcome and the complications after an average follow-up of 24.9
      months in 25 patients of proximal humeral fractures with osteoporosis. Mean age
      was 62 years. Using AO classification, 48% were type A and 52% type B. RESULTS:
      Mean constant score was 80 points. According to constant score, 28% had excellent
      outcome, 64% had good functional outcome, and 8% had moderate outcome. When the
      results were related to grades of osteoporosis, grade IV osteoporotic fractures
      had highest average Constant-Murley score (83 points, range 78-88 points),
      followed by grade III osteoporotic fractures (80 points, range 71-92 points),
      followed by grade II osteoporotic fractures (78 points, range 66-88 points).
      Varus malalignment and subacromial impingement were observed in 8% patients.
      Loosening of implant and loss of reduction were observed in 4% patients.
      Superficial infection was observed in 4% patients. CONCLUSIONS: Locking
      compression plate (LPHP) is an advantageous implant in proximal humeral fractures
      due to angular stability, particularly in comminuted fractures and in
      osteoporotic bones in elderly patients, thus allowing early mobilization.

PMID- 19384612
TI  - Quality of life evaluation in patients affected by osteoarthritis secondary to
      congenital hip dysplasia after total hip replacement.
AB  - BACKGROUND: The aim of the study was to evaluate the quality of life (QoL) in
      patients affected by osteoarthritis (OA) secondary to congenital hip dysplasia
      (CHD) and treated by hip arthroplasty. METHODS: We prospectively treated 40
      patients admitted to our hospital between 2001 and 2006. Each patient was asked
      to answer to two questionnaires: WOMAC and MOS SF-36. Patients were evaluated
      four months before surgery and once they had achieved postoperative
      rehabilitation. Pre- and postoperative results were analyzed and compared with
      the international literature on patients affected by OA and also with a healthy
      population. RESULTS: Pre- and post-operative results: WOMAC: pain 14.06-0.84;
      stiffness 4.26-0.52; function 42.68-5.39. SF-36: physical function 18.55-84.52;
      role physical 28.33-87.10; body pain 23.26-83.39; general health 55.19-81.74;
      vitality 32.74-72.10; social function 43.55-84.66; role emotional 68.82-93.55;
      mental health 48.77-79.35. All results were statistically significant.
      CONCLUSIONS: The study reports an important QoL improvement in patients affected
      by arthritis secondary to CHD that underwent hip surgery, and underlines
      differences with respect to primary OA. QoL evaluation cannot replace either
      clinical and instrumental evaluation or the physician's experience, but it can
      give weight to the patient's expectations, and may be considered an efficient
      test for medical and surgical treatments.

PMID- 19384613
TI  - Simultaneous chronic rupture of quadriceps tendon and contra-lateral patellar
      tendon in a patient affected by tertiary hyperparatiroidism.
AB  - Spontaneous ruptures of the extensor mechanism of the knee are very rare. They
      tend to increase considerably in patients with metabolic diseases such as chronic
      renal failure, hyperparathyroidism, diabetes, gout, and systemic lupus
      erythematosus. The reported case regards a 48-year-old man with chronic,
      spontaneous and simultaneous quadriceps, and contra-lateral patellar tendon
      rupture. The patient suffered from chronic renal failure and for the past year
      from tertiary hyperparathyroidism. Ruptured tendons were repaired and both knee
      were evaluated monthly for the next 12 months. Good functional recovery was
      achieved on both knees without relapse. This case emphasizes the importance of
      long-term high parathyroid hormone level in the etiology of tendons ruptures.

PMID- 19384614
TI  - Late post-operative paraparesis after rib penetration of the spinal canal in a
      patient with neurofibromatous scoliosis.
AB  - Rib displacement into the spinal canal is a rare cause of paraplegia or
      paraparesis in patients affected by neurofibromatous scoliosis. We describe a
      case of paraparesis in a 14-year-old child affected by neurofibromatous
      dystrophic kyphoscoliosis, treated with combined posterior and anterior spinal
      arthrodesis. Seventeen days after the surgical treatment the patient developed
      clinical signs and symptoms of paraparesis. A CT scan showed the head of the
      fifth rib protruding into the spinal canal with cord compression. Rib resection
      and posterior cord decompression were carried out following complete neurological
      recovery.

PMID- 19384615
TI  - Segond fracture with anterior cruciate ligament tear in an adolescent.
AB  - The authors report a case of acute knee injury in a 14-year-old teenager. The X
      ray showed a so-called Segond's fracture: a small avulsed bone fragment,
      elliptical in shape, lying immediately below the external tibial plateau, a few
      millimeters from the lateral tibial cortex. The fracture site was in the portion
      of the tibial condyle which is linked to the middle third of the lateral capsule
      by meniscal tibial fibers. Clinical examination under anesthesia and subsequent
      arthroscopy revealed a total intrasubstance ACL (anterior cruciate ligament) tear
      close to the proximal insertion. The authors confirm Segond's report of a
      possible association of this avulsion fracture with ACL injuries, even in
      adolescence.

PMID- 19384616
TI  - Tissue sparing surgery in knee reconstruction: unicompartmental (UKA),
      patellofemoral (PFA), UKA + PFA, bi-unicompartmental (Bi-UKA) arthroplasties.
AB  - Recently mini-invasive joint replacement has become one of the hottest topics in
      the orthopaedic world. However, these terms have been improperly misunderstood as
      a "key-hole" surgery where traditional components are implanted with shorter
      surgical approaches, with few benefits and several possible dangers. Small
      implants as unicompartmental knee prostheses, patellofemoral prostheses and bi
      unicompartmental knee prostheses might represent real less invasive procedures:
      Tissue sparing surgery, the Italian way to minimally invasive surgery (MIS).
      According to their experience the authors go through this real tissue sparing
      surgery not limited only to a small incision, but where the surgeons can respect
      the physiological joint biomechanics.

PMID- 19384617
TI  - Revision total hip arthroplasty using the Zweymuller femoral stem.
AB  - BACKGROUND: A variety of femoral stem designs have been reported to be successful
      in revision total hip arthroplasty without consensus as to optimal design. We
      evaluated the clinical and radiographic outcomes in a consecutive series of
      femoral revisions using a wedge-shape, tapered-stem design at medium and long
      term follow-up. MATERIALS AND METHODS: We performed a retrospective review of
      clinical and radiographic outcomes of twenty-eight consecutive femoral revisions
      arthroplasties, which were done using the Zweymuller femoral stem. RESULTS: The
      mean follow-up was 7.4 years (range 2-15 years). No stem re-revision was
      necessary. All stems were judged to be stable by radiographic criteria at the
      most recent follow-up. The final mean Harris hip score was 90. There was no
      difference in Harris hip scores, implant stability, or radiological appearance
      (distal cortical hypertrophy or proximal stress shielding) of the implants
      between medium-term (mean 5.7 years) and long-term (mean 12.4 years) follow-up.
      CONCLUSIONS: We found the Zweymuller femoral stem design to be durable for
      revision hip arthroplasty when there is an intact metaphyseal-diaphyseal junction
      for adequate press-fit stability at surgery.

PMID- 19384618
TI  - Effect of bioactive coating of the tibial component on migration pattern in
      uncemented total knee arthroplasty: a randomized RSA study of 14 knees presented
      according to new RSA-guidelines.
AB  - BACKGROUND: Bioactive coating of uncemented total knee arthroplasty (TKA) is
      believed to increase bone ingrowth and enhance early fixation of the TKA. In a
      prospective randomized study using radiostereometric analysis (RSA) we examined
      migrations of the tibial implant, in an uncemented TKA with and without bioactive
      coating. The study was performed according to new RSA guidelines, and focus was
      put on some important methodological issues. MATERIALS AND METHODS: Twenty-three
      patients with osteoarthrosis of the knee received an uncemented Duracon TKA
      either with bioactive (hydroxyapatite or periapatite) coating (+HA) or without
      bioactive coating (-HA). Patients had RSA examinations postoperatively and at 3,
      6 and 12 months. Nine patients were excluded during the study resulting in 14
      knees for final analysis. RESULTS: At 12 months follow-up we found no significant
      differences in migrations between the two groups. However, in general the -HA
      group migrated more than the +HA group, and we found a significant larger
      variation in migration pattern in the -HA group. In the +HA group the tibia
      component stabilized after 6 months, whereas the -HA group showed continuous
      migration. Subsidence and posterior tilt were the main migration patterns in both
      groups. CONCLUSIONS: Bioactive coating of TKA seems to enhance early
      stabilization of the tibia component. Similar results are found in previous
      studies.

PMID- 19384619
TI  - Late collapse of distal radius fractures after K-wire removal: is it significant?
AB  - BACKGROUND: The aim of this study was to find out whether distal radius fractures
      treated by Kirschner wire (K wire) fixation loose reduction after wire removal
      and analyze the variables may influence this. MATERIALS AND METHODS: Patients who
      underwent K wire fixation for unstable fractures of distal radius over a period
      of 3 years were included in this retrospective study. Fractures were classified
      according to AO classification. Radiographs taken just prior to removal of K
      wires and radiographs taken at least 1 month after wire removal were analyzed to
      study three radiological parameters; Palmar or dorsal tilt, radial inclination
      and ulnar variance. Loss of these angles was analyzed statistically against
      variables like age, sex, AO classification and duration of fixation. RESULTS: 59
      fractures were analyzed with mean age of 56 years and male to female ratio of
      1:2. Average loss of radial tilt was 2.6 degrees , loss of palmar tilt was 2.6
      degrees and loss of ulnar variance was 1.3 mm. CONCLUSIONS: We found that distal
      radius fractures treated by percutaneous K wire fixation, did not suffer
      significant loss of reduction of fracture position after removal of wires. This
      remains true regardless of age, sex, fracture type according to AO type or
      duration of wire fixation.

PMID- 19384620
TI  - Xenogenic demineralized bone matrix and fresh autogenous cortical bone effects on
      experimental bone healing: radiological, histopathological and biomechanical
      evaluation.
AB  - BACKGROUND: Bone grafting is used to enhance healing in osteotomies, arthrodesis,
      and multifragmentary fractures and to replace bony loss resulting from neoplasia
      or cysts. They are source of osteoprogenitor cells and induce bone formation and
      provide mechanical support for vascular and bone ingrowth. Autografts are used
      commonly but quantity of harvested bone is limited. The aim of this study is to
      evaluate autograft and new xenogenic bovine demineralized bone matrix (DBM)
      effects on bone healing process. MATERIALS AND METHODS: Twenty male White New
      Zealand rabbits were used in this study. In group I (n = 10) the defect was
      filled by xenogenic DBM and in autograft group the defect was filled by fresh
      autogenous cortical graft and fixed by cercelage wire. Radiological,
      histopathological and biomechanical evaluations were performed blindly and
      results scored and analyzed statistically. RESULTS: Statistical tests did not
      reveal any significant differences between two groups on the 14th postoperative
      day radiographically (P > 0.05). There was a significant difference for union on
      28th and 42nd postoperative days and for remodeling at on the 56th postoperative
      day radiologically (P < 0.05). Statistical tests did not support any significant
      differences between two groups for radiological bone formation (P > 0.05).
      Histopathological and biomechanical evaluation revealed no significant
      differences between two groups. CONCLUSIONS: The results of this study indicate
      that satisfactory healing occurred in rabbit radius defect filled with xenogenic
      bovine DBM. Complications were not identified and healing was faster, same as in
      cortical autogenous grafting.

PMID- 19384621
TI  - Biomarkers, type II collagen, glucosamine and chondroitin sulfate in
      osteoarthritis follow-up: the "Magenta osteoarthritis study".
AB  - BACKGROUND: The purpose of the present study was to determine relationship
      between disease activity, systemic markers of cartilage degradation, urinary C
      terminal cross-linking telopeptides of type II collagen (uCTX-II), and bone
      degradation, urinary C-terminal cross-linking telopeptides of type I collagen
      (uCTX-I), structural progression of osteoarthritis (OA) and potential therapeutic
      efficacy of type II collagen (COLLII) in combination with glucosamine and
      chondroitin sulfate (GC). MATERIALS AND METHODS: An observational retrospective
      study, 1-year follow-up, on 104 patients with OA (nodular osteoarthritis of the
      hand, erosive osteoarthritis of the hand, EOA, osteoarthritis of the knee or hip)
      who were treated with GC or glucosamine, chondroitin sulfate and collagen type II
      (GCC). The following information was collected at entry: demographics, BMI,
      characteristics of OA, patient global assessment (VAS), C-terminal cross-linking
      telopeptides of collagen types I (uCTX-I) and II (uCTX-II) and radiographs. After
      6 months: VAS, uCTX-I and uCTX-II. After 1 year: VAS, uCTX-I, uCTX-II and
      radiographs. RESULTS: After 6 months and 1 year of treatment VAS, uCTX-I and uCTX
      II mean values were significantly lower than the baseline. 57 were treated with
      GCC and 47 with GC. The group that received GCC showed a similar VAS mean value
      after 6 months and 1 year when compared with the group treated with GC. uCTX-I
      and uCTX-II mean level was lower in the group treated with GCC (P < 0.05).
      Radiological score (Kellgren and Lawrence summarized score for hands) after 1
      year showed a reduced progression compared to the baseline in the hand
      osteoarthritis group, especially after GCC treatment (P < 0.05). Finally, uCTX-I
      has better correlation with radiological score and with GC in the EOA subgroup
      (Pearson index: R = 0.44). CONCLUSIONS: (a) uCTX-I and uCTX-II proved to be
      useful biomarkers in OA monitoring; (b) uCTX-I is better correlated with hand EOA
      and could represent a potential further marker to assess the evolution of EOA
      bone damage; (c) GC slow down OA progression; (d) finally COLLII could represent
      a further protective factor in OA cartilage.

PMID- 19384622
TI  - A treatment protocol for abdomino-pelvic injuries.
AB  - BACKGROUND: Abdomino-pelvic injuries often present a challenge for the emergency
      department. Although literature reports several protocols on the treatment of
      abdomino-pelvic injuries aiming at defining the most advisable treatment line,
      optimal treatment is still controversial. This paper describes a protocol that
      has been used to treat abdomino-pelvic injuries in our hospital since 2002.
      MATERIALS AND METHODS: In literature different protocol of abdomino-pelvic
      injuries are described and comparing them most of the difference are the timing
      of CT scan, the angiography and the laparotomy when treating a lesion of pelvic
      ring. If patient is haemodynamically instable and presents a lesion of pelvic
      ring our protocol suggest the simplest and fastest stabilization (pelvic external
      fixator) in emergency room and delay exam such as CT scan as second level exam.
      In the presence of an abdominal injury, with a positive focused assessment with
      sonography for trauma test, the first step should be a pelvic ring stabilization,
      as laparotomy decreases the abdominal pressure and reduces the tamponade effect
      on the retroperitoneum. According to presented protocol the angiography is not be
      a first choice treatment. This protocol was applied to 58 cases of abdomino
      pelvic injury with unstable pelvic lesions from October 2002 to December 2005.
      Mean injury severity score was 27.2 (CI 24.1-30.3). RESULTS: Five patients (8%)
      died, three due to haemorrhagic shock and two due to pulmonary embolization. Four
      patients (6.9%) had a partial or complete cauda equina syndrome, four patients
      (6.9%) complained of mild incontinence, whilst 1 (1.7%) complained of urinary
      retention with multiple cystitis. Two patients (3.4%) with retention and multiple
      cystitis, had a malunion and a painful non-union of the fracture. Seven patients
      (12.3%) had neurological impairment: 5 (8.6%) sciatic nerve palsy, 1 (1.7%)
      lumbosacral root lesions in a C2-type fracture and there was one case (1.7%) of
      inconstant lumbago with sciatic pain. Twelve patients reported different levels
      of sexual dysfunction (20.7%). CONCLUSIONS: Although validation with a larger
      cohort is required, our preliminary clinical data are similar to, or better than,
      those reported in the most recent publications on this question, suggesting that
      this protocol could well reduce both the mortality rate and the long term
      complications of abdominopelvic injuries.

PMID- 19384623
TI  - Delayed union of an operated fracture of the femoral neck.
AB  - Fracture of the femoral neck continues to be a vexing clinical and therapeutic
      challenge for the orthopedic surgeon. The fracture has a propensity for non-union
      and avascular necrosis. It is a challenge for the orthopedic surgeon to decide
      when to intervene in a case with non-union where the implant continues to be in
      place. We present a case with persistent clinical and radiological non-union
      signs where the fracture eventually united after 32 months. The case bolsters the
      view that a continued conservative regime might entail good results in such
      situations.

PMID- 19384624
TI  - Spontaneous compartment syndrome in a patient with diabetes and statin
      administration: a case report.
AB  - Compartment syndrome is a condition characterized by pressure increasing in the
      inextensible muscular compartments that leads to a decrease of capillary
      perfusion with consequent ischemic lesions of the logia elements. The authors
      report a case of an unusual compartment syndrome with spontaneous onset in a
      patient with type II diabetes and chronic therapy with statins (Atorvastatin).
      The condition was successfully treated by a fasciotomy and medical support. The
      importance of a correct anamnesis and a high level of suspicion is emphasized.

PMID- 19384625
TI  - Treatment of acute grade III acromioclavicular dislocation: a lack of evidence.
AB  - BACKGROUND: Although nonoperative treatment is considered the standard of care
      for the treatment of grade I and II acromioclavicular joint injuries, the
      treatment of grade III injuries is controversial. There are as many methods of
      nonoperative treatment as there are for operative stabilization. That is why we
      conducted a literature research to find out the best evidence regarding the
      treatment of acute grade III acromioclavicular dislocation. METHOD: The research
      was limited to RCTs, systematic review and meta-analysis in the most
      representative databases. Even if research identifies more than 600 articles,
      only five were included in the study because there were RCTs, and systematic
      reviews, but no meta-analysis articles were found. Moreover, no meta-analysis was
      performed because of differences of data published in the three RCTs (different
      type of surgical treatments and different outcome measures). RESULTS: From the
      literature evaluation, clinical results seem to be comparable between the
      operative and the conservative treatments, but complications are more evident in
      the surgery group. Since there is not a preponderance of positive papers showing
      the benefits of a surgical technique over conservative therapy, the nonoperative
      treatment is still considered a valid procedure in the grade III
      acromioclavicular separation. CONCLUSION: More prospective randomized studies
      using validated outcome measures are needed to identify the suitable operation
      techniques for the acute injuries.

PMID- 19384627
TI  - Abstract book - 93rd national congress of the italian society of orthopaedics and
      traumatology.

PMID- 19384626
TI  - The role of dedicated instrumentation in total hip arthroplasty.
AB  - Tissue-sparing surgery is a surgical strategy aimed to reduce tissue damage in
      joint replacement. This can be achieved by reducing soft tissue trauma,
      performing minimally invasive access routes and limiting bone removal with
      implantation of conservative prostheses. In order to facilitate mini-approaches,
      special instrumentation was developed to avoid impingement of the soft tissues
      and provide an easier and more correct placement of the components. We performed
      an analysis of the literature and a research of the instrumentation available
      today, to evaluate the actual utility of dedicated tools.

PMID- 19384628
TI  - UHMWPE for arthroplasty: past or future?
AB  - Wear debris related osteolysis is recognised as being the main cause of failure
      in joint replacements based on UHMWPE inserts. However, many solutions and "new"
      polyethylenes have been suggested in order to address this issue. This review
      discusses "historical" issues associated with UHMWPE, such as oxidation,
      sterilization method and storage, as well as "new" topics, such as crosslinking
      and stabilization. The final aim is to aid orthopaedic surgeons in their
      selection of polyethylene inserts and in the information given to the patients.
      The main problem for the polymer is degradative oxidation, which is caused by the
      combination of the irradiation used for sterilization and oxygen, and which leads
      to a decrease in wear resistance and mechanical properties. Irradiation and
      packaging in the absence of oxygen can only reduce the oxidation, while
      sterilization with gas (EtO or gas plasma) is the only method that effectively
      eliminates it. Manufacturing processes are of great relevance to the clinical
      duration and must be considered by surgeons. Crosslinked polyethylene has been
      developed for joint inserts due to its superior wear resistance compared to
      conventional UHMWPE; to prevent the oxidation, crosslinked polyethylene requires
      post-irradiation thermal treatment, which reduces its mechanical properties and
      which depends on the producer. Several good clinical results from the use of
      crosslinked acetabular cups have reported at mid-term, while early results for
      knee replacements are also encouraging. Recently, the use of the antioxidant
      vitamin E (alpha-tocopherol) has been introduced for joint prostheses in order to
      prevent the oxidation of both crosslinked and noncrosslinked UHMWPE.

PMID- 19384629
TI  - The use of circular fine wire frames for the treatment of displaced intra
      articular calcaneal fractures.
AB  - BACKGROUND: The treatment of displaced intra-articular calcaneal fractures is
      still controversial. MATERIALS AND METHODS: Sixteen consecutive patients admitted
      at University Hospital with intra-articular fractures were treated with fine wire
      circular frames and followed up at an average of 160 days from their injuries. We
      focused on radiological outcome and functional outcome using a patient-based
      questionnaire. RESULTS: We had no secondary reconstruction procedures. With the
      numbers available, the difference between the preoperative values and the follow
      up measurements for Bohler's angle, Gissane's angle and posterior subtalar joint
      space was not statistically significant (P = 0.8, P = 0.2, and P = 0.4,
      respectively). The standardized AAOS FAS ranged from 42 to 96, with a mean of 80
      and a standard deviation of 19. CONCLUSIONS: Fine wire circular frame is a good
      alternative to ORIF in displaced intra-articular calcaneal fractures, yielding
      good patient function, a high return-to-work rate and a low complication rate.

PMID- 19384630
TI  - The external rotation method for reduction of acute anterior shoulder
      dislocations.
AB  - BACKGROUND: Shoulder dislocations account for almost 50% of all joint
      dislocations, and are most commonly anterior (90-98%) and occur due to trauma.
      This prospective study was conducted to report our experiences of using the
      external rotation method (ERM) in the reduction of acute anterior shoulder
      dislocation. MATERIALS AND METHODS: Between August 2006 and April 2007, ERM was
      applied to 31 patients who presented with traumatic anterior shoulder dislocation
      to the Emergency Department of our Hospital which is a level 2 trauma centre. We
      evaluated the type of dislocation, the effectiveness of the procedure in
      achieving reduction, the need for premedication, the ease of performing the
      reduction, and complications, if any. RESULTS: Of the 31 patients, 29 had a
      successful reduction. No premedication was required in 25 patients who had a
      successful reduction, and the average time required for reduction in 25 was less
      than 2 min. Only five patients reported severe pain during the process of
      reduction. The method was not successful in two patients in whom the reduction
      was achieved under narcosis. We experienced a success rate of 89% at the first
      attempt. None of the patients encountered any complication. CONCLUSIONS: ERM for
      the reduction of acute anterior dislocation of the shoulder is a safe and
      reliable method, mainly without requirement for any sedatives or opiate
      analgesics, that can be performed relatively painlessly for anterior shoulder
      dislocations. As no single method has a 100% success rate, ERM is a useful one to
      know.

PMID- 19384631
TI  - Cervical degenerative index: a new quantitative radiographic scoring system for
      cervical spondylosis with interobserver and intraobserver reliability testing.
AB  - BACKGROUND: The lack of a widely available scoring system for cervical
      degenerative spondylosis encouraged the authors to establish and validate a
      systematic quantitative radiographic index. MATERIALS AND METHODS: This study
      included intraobserver and interobserver reliability testing among three
      reviewers with different years of experience. Each observer independently scored
      four cervical radiographs of 48 patients at separate intervals, and statistical
      analysis of the grading was performed. RESULTS: There was high intraobserver and
      interobserver reliability between the two experienced observers. There was fair
      reliability between the less experienced observer and the more experienced
      observers. CONCLUSIONS: The cervical degenerative index appears to be a reliable
      and reproducible radiographic assessment of cervical spondylosis. The index will
      have direct applicability for longitudinal study of cervical spondylosis and may
      be clinically relevant as well.

PMID- 19384632
TI  - Cervical degenerative changes in idiopathic scoliosis patients who underwent long
      fusion to the sacrum as adults: incidence, severity, and evolution.
AB  - BACKGROUND: To date, there have been no published studies of the degenerative
      changes in the cervical spine in adult idiopathic scoliosis patients with
      thoracic and lumbar curves severe enough to require major reconstructive surgery.
      MATERIALS AND METHODS: The primary study group was 48 adult patients who had
      previously undergone a fusion from T10 or higher to the sacrum as an adult for
      idiopathic scoliosis. These were compared to 38 adults with unfused idiopathic
      scoliosis of 30 degrees -50 degrees and to 42 symptomatic adults presenting with
      cervical pain. Cervical degeneration was assessed using a new cervical
      degenerative index (CDI). RESULTS: The amount of degenerative change seen in the
      cervical spine in the long-fusion group was significantly higher at baseline
      (just prior to the fusion) than the two control populations and became much
      higher at a mean follow-up of 8.5 years. CONCLUSIONS: This unique subgroup of
      patients, those having fusion from the thoracic spine to the sacrum as adults for
      adolescent idiopathic scoliosis, had a high incidence and severity of
      degenerative changes in their cervical spine. Due to the presence of advanced
      cervical degenerative changes prior to the fusion, it is not possible to blame
      the fusion as the main cause for these findings. These changes are either related
      to the thoracic and lumbar deformities or are more likely due to this subgroup
      having a higher natural propensity for degenerative changes.

PMID- 19384633
TI  - A case of relapsing Salmonella osteomyelitis in a thalassaemia trait patient.
AB  - We report a case of chronic relapsing osteomyelitis caused by Salmonella Stanley
      in a beta-thalassaemia trait patient who is otherwise normal. The importance of
      obtaining definitive bacteriological diagnosis and timely intervention to treat
      bone infection effectively is emphasised here.

PMID- 19384634
TI  - Femoral neck fracture following intramedullary nailing with misplacement of an
      end cup: report of two cases.
AB  - Femoral neck fracture is an unusual complication of intramedullary fixation of a
      broken femur. We report on two cases of femoral neck fractures attributed to
      misplacement of an end cup and subsequent invasive maneuvers in an effort to
      remove it. Iatrogenic fractures of the femoral neck during or after
      intramedullary nailing are reported in the medical literature. Authors associate
      it with many possible technical mistakes performed during the procedure, yet no
      complications after missed end cup placement were noted. We suggest that the
      fractures described below were a consequence of injury to the vascular supply and
      bone stock of the initially intact femoral neck.

PMID- 19384635
TI  - Early catastrophic acetabular failure in Furlong total hip replacements.
AB  - The use of uncemented hip arthroplasty prostheses with ceramic articulations are
      popular, especially in the young, because of a perceived reduction in wear. We
      highlight a complication of ceramic on polyethylene articulating couples not
      previously described in the Furlong replacement. Despite widespread metalosis and
      particulate debris, osteolysis was not initially seen. The contamination
      compromised subsequent revision.

PMID- 19384636
TI  - Dysplasia epiphysealis hemimelica of the talus.
AB  - Dysplasia epiphysealis hemimelica is a rare developmental disorder with unknown
      etiology affecting epiphysis in childhood. The lesion is an osteochondroma
      arising from the epiphysis and increasing in size until skeletal maturity is
      reached. Surgical treatment is mandatory when symptoms such as pain, joint
      impingement or deformation are present, and yields good results when the mass is
      juxtaarticular or extraarticular. In those cases where articular symptoms are not
      present and only mass evolution is observed, surgical treatment is not
      recommended before skeletal maturity has been reached. A case of DEH located in
      the talus and successfully treated with surgery is presented.

PMID- 19384638
TI  - Ultrasound in emergency medicine: a colorful future in black and white.

PMID- 19384637
TI  - Learning curve in tissue sparing total hip replacement: comparison between
      different approaches.
AB  - BACKGROUND: The tissue sparing surgery (TSS) concept means not only smaller
      incisions but also less tissue disruption, allowing decreased blood loss and
      improved function. However, TSS techniques can result in more complications
      related to the learning curve. The aim of this study was to compare the learning
      curve of an experienced surgeon with different TSS approaches for total hip
      replacement (THR) from a clinical and surgical point of view, focussing
      especially on complications related to the use of different geometric stems.
      MATERIALS AND METHODS: Sixty patients scheduled to be operated for a primary THR
      were enrolled in the study and were randomly assigned to surgery by one of three
      different TSS approaches: lateral with mini incision (group A), minimally
      invasive anterior (group B) and minimally invasive antero-lateral (group C).
      Results from the three TSS groups were compared with a control group of 149
      patients (group D). RESULTS: Our results reveal significantly reduced blood loss
      in the TSS groups compared with the control group, with no differences between
      the TSS groups. We found better early functional scores in the two minimally
      invasive groups (anterior and anterolateral), and a lower rate of complications
      with the antero-lateral TSS approach. CONCLUSION: The antero-lateral TSS approach
      seems to be safer and less demanding than standard THR surgery, and is suitable
      for use with different stems.

PMID- 19384640
TI  - Introduction of a portable ultrasound unit into the health services of the Lugufu
      refugee camp, Kigoma District, Tanzania.
AB  - BACKGROUND: Diagnostic imaging services are scarce in much of the developing
      world. Ultrasound is a low-cost, safe, and widely applicable imaging modality.
      AIMS: We delivered a portable ultrasound machine to the Lugufu refugee camp in
      Tanzania and conducted a course on its use in order to assess the feasibility of
      introducing this technology into a very low-resource setting. METHODS: We
      conducted an intensive 4-day ultrasound training course for health care providers
      at Lugufu and established an exam logbook to track the frequency of use,
      distribution of ultrasound applications, and gender and age distribution of
      patients. RESULTS: Between 4 October 2005 and 1 November 2007 547 separate
      ultrasound exams on 460 patients were recorded at Lugufu. Overall, 86% of
      patients studied were female. Pregnancy-related exams accounted for 24.1% of
      total usage. The 20- to 29-year-old age group accounted for over one third of
      total exams performed. CONCLUSION: Ultrasound is a feasible and sustainable
      imaging modality in a very low-resource setting such as the Lugufu refugee camp
      in Tanzania.

PMID- 19384639
TI  - Use of ultrasound by emergency medical services: a review.
AB  - Prehospital ultrasound has been deployed in certain areas of the USA and Europe.
      Physicians, emergency medical technicians, and flight nurses have utilized a
      variety of medical and trauma ultrasound assessments to impact patient care in
      the field. The goal of this review is to summarize the literature on emergency
      medical services (EMS) use of ultrasound to more clearly define the potential
      utility of this technology for prehospital providers.

PMID- 19384641
TI  - Ultrasound as an aid for reduction of paediatric forearm fractures.
AB  - BACKGROUND: Displaced distal forearm fractures are frequently reduced in
      emergency departments. Not infrequently, some are not done adequately and require
      the tedious process of repeating the procedure, with repeated X-rays and
      radiation exposure, and inconvenience to patient and staff. The use of ultrasound
      (US) in its expanding role in the practice of emergency medicine has been
      proposed to visualise bone positioning. AIM: Our department embarked on this
      proof of concept study to assess the usefulness of this tool. METHOD: By way of
      convenience sampling, we looked at whether our US interpretation correlated with
      the corresponding X-ray findings, pre and post manipulation of suitable
      fractures. RESULTS: Out of 42 patients recruited over a 1-year period, we were
      successful in 38 (90%). Four were "unsuccessful" (10%) due to technique rather
      than equipment or patient factors. CONCLUSION: Whilst before we were blind prior
      to a post-reduction X-ray, this "new" additional role of the ultrasound (very
      accessible, cost effective and safe) can now aid us in our decision making,
      thereby enhancing the work flow of this group of patients through the department.

PMID- 19384642
TI  - The current state of hospital-based emergency medicine in Germany.
AB  - Germany has a long tradition of having physicians, often anesthesiologists with
      additional training in emergency medicine, deliver prehospital emergency care.
      Hospital-based emergency medicine in Germany also differs significantly from the
      Anglo-American model, and until recently having separate emergency rooms for
      different departments was the norm. In the past decade, many hospitals have
      created "centralized emergency departments" [Zentrale Notaufnahme (ZNAs)]. There
      is ongoing debate about the training and certification of physicians working in
      the ZNAs and whether Germany will adopt a specialty board certification for
      emergency medicine.

PMID- 19384643
TI  - In-process modification yields improved teaching outcomes for international
      emergency medicine.
AB  - AIMS: To determine if on-going modification of an international teaching course
      in emergency medicine will improve audience perception and receptivity. METHODS:
      Over 4 years, we conducted surveys during emergency medicine symposiums given in
      Ghana, West Africa. In 2003, 2004 and 2006, symposium interventions of content
      modification (lecture topics/workshops), audience modification (smaller groups,
      designing workshops for different levels of providers) and in-process
      modification (modification of lecture technique in two sequential 2006
      symposiums) were done. Survey responses were analyzed to determine what
      interventions resulted in greater participant satisfaction. When comparing the
      three groups, a one-way ANOVA test was conducted to determine differences among
      the 3 years. When comparing two groups, Levene's test for equality of variances
      was conducted for annual variance, and based on that result, an independent t
      test was calculated. RESULTS: The one-way ANOVA test indicated that there was a
      statistically significant difference among the three groups (2003, 2004, 2006) of
      symposium participants in four questions related to the participants' perception
      of the instructors. The independent t-test comparing the aggregate data of 2003
      and 2004 with 2006 (audience modification and in-process modification between two
      sequential symposiums) showed a statistically significant improvement in the
      participants' receptivity. The data indicated that modifying the content of
      international symposiums and modifying the audience to which it is addressed are
      equally valuable tools to ensure a positive participant receptivity. Moreover,
      the data indicated that "in-process" modification conducted between the two
      sequential 2006 symposiums produced a statistically significant increase in
      positive perception, facilitating knowledge transfer. CONCLUSION: Statistical
      analysis of surveys coupled with modification and intervention can improve
      participant satisfaction in international teaching programs.

PMID- 19384644
TI  - Emergency department utilization by HIV-positive adults in the HAART era.
AB  - BACKGROUND: No published study has analyzed emergency department (ED) utilization
      by human immunodeficiency virus (HIV)-positive adults in the highly active
      antiretroviral therapy (HAART) era. AIMS: The purpose of this study is to
      describe the demographic and HIV-specific variables associated with ED
      utilization by HIV-positive adults and their diagnoses when discharged from the
      ED or subsequently from the hospital. METHODS: We conducted a retrospective
      cohort study of all HIV-positive adults cared for at a tertiary center HIV clinic
      and ED (1 January-31 December 2006). Demographic, HIV clinical, and HIV lab
      variables were abstracted from the clinic database. ED/hospital diagnoses coded
      by the ICD-9 Diseases/Injuries Tabular Index were abstracted from identified
      discharge records. We used multivariate logistic regression to compute odds
      ratios (OR) of ED utilization based on the abstracted variables. We described the
      cohort and diagnoses using descriptive statistics. RESULTS: A total of 356
      patients met inclusion criteria. Their mean age was 42.7 years, and 77.2% of
      included patients were male; 52.5% were Caucasian and 47.5% non-Caucasian; 72
      patients (20.2%) presented to the ED during the study period [153 visits; 37
      (10.4%) required hospitalization (61/153 visits)]. Income level and mean 2006
      viral load had a significant association (p < 0.05) with ED utilization. Of 155
      ICD-9 ED discharge diagnoses, ill-defined symptoms/signs (25.2%), injury (18.7%),
      and musculoskeletal disorders (11.6%) were most prevalent. Of 450 ICD-9 hospital
      discharge diagnoses, endocrine/metabolic (13.3%), psychiatric (12.2%),
      infectious/parasitic (12%), and circulatory disorders (11.8%) were most
      prevalent. CONCLUSION: In this study of HIV-positive adults, income level and
      mean 2006 viral load had a significant association with ED utilization.
      Noninfectious diagnoses were alone most prevalent in ED discharged, but not
      hospitalized, patients.

PMID- 19384645
TI  - A national Internet survey on rapid sequence intubation patterns from Turkey.
AB  - AIM: To determine which specialty was performing rapid sequence intubation (RSI)
      in the emergency departments and to determine drug preferences of emergency
      physicians during RSI in Turkey. METHOD: All emergency departments were contacted
      via e-mail, and the chiefs of the departments were requested to answer a survey
      consisting of six questions. Hospitals within the specified regions were selected
      with the only inclusion criteria being that the hospital had an emergency
      medicine department. We determined that there were 32 university and 9 state
      hospital emergency medicine residency programs. RESULTS: Thirty-five emergency
      departments responded. In 31 (73%) departments emergency medicine physicians, in
      4 (10%) departments anesthetists, and in 7 (17%) departments physicians of either
      specialty were routinely performing RSI. The most commonly preferred drugs were
      fentanyl for premedication, vecuronium for defasciculation, etomidate for
      induction, and succinylcholine for neuromuscular blocking. CONCLUSION: In the
      majority of the emergency departments in Turkey, emergency medicine physicians
      perform the RSI; the anesthetists perform it in only a few departments.

PMID- 19384646
TI  - The willingness of final year medical and dental students to perform bystander
      cardiopulmonary resuscitation in an Asian community.
AB  - BACKGROUND: Despite the importance of early effective chest compressions to
      improve the chance of survival of an out-of-hospital cardiac arrest victim, it is
      still largely unknown how willing our Malaysian population is to perform
      bystander cardiopulmonary resuscitation (CPR). AIMS: We conducted a voluntary,
      anonymous self-administered questionnaire survey of a group of 164 final year
      medical students and 60 final year dental students to unravel their attitudes
      towards performing bystander CPR. METHODS: Using a 4-point Likert scale of
      "definitely yes," "probably yes," "probably no," and "definitely no," the
      students were asked to rate their willingness to perform bystander CPR under
      three categories: chest compressions with mouth-to-mouth ventilation (CC + MMV),
      chest compressions with mask-to-mouth ventilation (CC + PMV), and chest
      compressions only (CC). Under each category, the students were given ten
      hypothetical victim scenarios. Categorical data analysis was done using the
      McNemar test, chi-square test, and Fisher exact test where appropriate. For
      selected analysis, "definitely yes" and "probably yes" were recoded as a
      "positive response." RESULTS: Generally, we found that only 51.4% of the medical
      and 45.5% of the dental students are willing to perform bystander CPR. When
      analyzed under different hypothetical scenarios, we found that, except for the
      scenario where the victim is their own family member, all other scenarios showed
      a dismally low rate of positive responses in the category of CC + MMV, but their
      willingness was significantly improved under the CC + PMV and CC categories.
      CONCLUSION: This study shows that there are unique sociocultural factors that
      contribute to the reluctance of our students to perform CC + MMV.

PMID- 19384647
TI  - A treatment protocol including vasopressin and hydroxyethyl starch solution is
      associated with increased rate of return of spontaneous circulation in blunt
      trauma patients with pulseless electrical activity.
AB  - BACKGROUND: Survival after cardiopulmonary resuscitation (CPR) using standard
      vasopressor therapy is disappointing. Vasopressin is a potent vasopressor that
      could become a useful therapeutic alternative in the treatment of cardiac arrest.
      AIMS: The aim of this prehospital prospective cohort study was to assess the
      influence of treatment with vasopressin and hydroxyethyl starch solution (HHS) on
      outcome in resuscitated blunt trauma patients with pulseless electrical activity
      (PEA) cardiac arrest. METHODS: Two treatment groups of resuscitated trauma
      patients in cardiac arrest were compared: in the epinephrine group patients
      received epinephrine 1 mg IV every 3 min only; in the vasopressin group patients
      first received hypertonic HHS and arginine vasopressin 40 units IV only or
      followed by epinephrine 1 mg every 3 min until cessation of CPR. Medical trauma
      care was provided according to advanced trauma life support (ATLS) guidelines.
      RESULTS: The study included 31 patients and there were no significant demographic
      or clinical differences between the treatment groups. Significantly more
      circulatory restorations [11/13 (85%) vs 3/18 (17%); P < 0.01] and better 24-h
      survival rates [8/13 (62%) vs 2/18 (11%); P = 0.001] were observed in the
      vasopressin group. Average mean arterial pressure (100.4 +/- 11.4 mmHg vs 80.3 +/
      12.4 mmHg) and final end-tidal partial pressure of carbon dioxide (PETCO(2)) at
      admission (4.5 +/- 0.9 kPa vs 2.8 +/- 0.4 kPa) were also higher in the
      vasopressin group. CONCLUSION: Our results suggest that victims of severe blunt
      trauma with PEA should be initially treated with vasopressin in combination with
      HHS volume resuscitation followed by standard resuscitation therapy and other
      procedures when appropriate. Vasopressin might be potentially lifesaving in blunt
      trauma cardiac arrest compared to standard treatment with epinephrine.

PMID- 19384648
TI  - The role of emergency department HIV care in resource-poor settings: lessons
      learned in western Kenya.
AB  - The human immunodeficiency virus (HIV) pandemic in sub-Saharan Africa and other
      high prevalence regions continues to overwhelm health care systems. While there
      has been a global response to improve the delivery of antiretroviral therapy in
      these high prevalence regions, there are few models that have developed an
      adequate plan to deal with HIV specifically in resource-poor emergency department
      settings. In this manuscript, we report on the experience scaling up HIV care at
      one emergency department in a large referral hospital located in western Kenya.
      Specifically, we describe how rapid bedside HIV testing helps to narrow the
      differential diagnosis of disease processes in acute care patients and how HIV
      screening of patients discharged from the emergency department can detect HIV
      infected individuals.

PMID- 19384649
TI  - Pre-formatted written discharge summary-a step towards quality assurance in the
      emergency department.
AB  - BACKGROUND: Providing discharge instructions to emergency department (ED)
      patients is not a standard practice and there is wide disparity in its
      implementation. There is evidence that ED discharge instructions, especially a
      pre- formatted one, complements verbal instructions and improves patient
      communication and management. AIMS: Our aim was to audit the practice of
      providing a discharge summary in a standardized pre-formatted form to patients
      visiting the ED at Sundaram Medical Foundation (SMF), Chennai, India. METHODS:
      Case sheets of 200 patients who visited the ED from 1 July to 31 August 2007 were
      selected randomly and were assessed for the documentation of the demographic and
      clinical details in the retained copy of the discharge summary by three medical
      records personnel independently. Descriptive analysis was used to measure
      frequency and percentages. RESULTS: All patients (100%) received a discharge
      summary and a carbon copy of the same was retained in the hospital. Demographic
      data, diagnosis, prescription and discharge instructions were written in > 80%.
      Legibility of the three important sections, namely diagnosis, prescription and
      discharge instructions, were 66, 76 and 65%, respectively. The diagnosis was
      written in an abbreviated form in 27%. The patient's signature was obtained in
      80%, while doctors signed in 89%. Investigation results and follow-up advice were
      not documented in 85 and 93%, respectively. CONCLUSION: The pre-formatted
      discharge summary provided more information than a prescription form in terms of
      the amount of information written by virtue of its structured nature.
      Deficiencies did reflect a resistance to change current practices in spite of
      having a structured data sheet. Physician and staff education could overcome
      this.

PMID- 19384650
TI  - Board review course effect on resident in-training examination.
AB  - BACKGROUND: The in-training examination is a national and yearly exam
      administered by the American Board of Emergency Medicine to all emergency
      medicine residents in the USA. The purpose of the examination is to evaluate a
      resident's progress toward obtaining the fundamental knowledge to practice
      independent emergency medicine. AIMS: The purpose of this study was to determine
      the effects of a 40 hour board review lecture course on the resident in-training
      examination in emergency medicine. METHODS: A 40 hour board review lecture course
      was designed and implemented during the weekly 5 hour long resident conferences
      during the 8 weeks preceding the in-training examination date in 2006. Attendance
      was mandatory at the Accreditation Council for Graduate Medical Education (ACGME)
      standard of 70% or greater. A positive result was considered to be a 10% increase
      or greater in the resident's individual national class percentile ranking among
      their national peers for their class year for the emergency medicine in-training
      examination. A resident was excluded from the study if there was no 2005 in
      training examination score for self-comparison. The 95% confidence intervals (CI)
      were used to analyze the results. RESULTS: Of 16 residents, 1 (6.25%; 95% CI: 0
      18%) showed a positive result of increasing their national class percentile
      ranking by 10% or greater. For the PGY2, one of the eight had a positive result
      (12.5%; 95% CI: 0-35.4%). For PGY3, no resident (0%; 95% CI: 0-35.4%) had a
      positive result. CONCLUSIONS: A 40 hour board review lecture course has no
      positive effect on improving a resident's in-training examination score.

PMID- 19384651
TI  - Primary pyomyositis caused by ca-MRSA.

PMID- 19384652
TI  - Diospyrobezoar: an uncommon cause of obstructive ileus.

PMID- 19384653
TI  - Research and mentorship as cornerstones of advancing academic emergency medicine
      globally.

PMID- 19384654
TI  - State of emergency medicine in South Africa.
AB  - INTRODUCTION: Emergency medicine is a new speciality in South Africa. It was
      first registered in 2003, and there are now 30 specialists in the country, with
      10 new graduates from local registrar training programmes and over 40 trainees on
      four programmes across the country. CONCLUSION: Emergency medicine is currently
      enjoying a governmental focus as part of the preparations towards the FIFA 2010
      soccer World Cup. This article discusses the current structure of emergency care
      in South Africa.

PMID- 19384655
TI  - The use of simulation in the education of emergency care providers for cardiac
      emergencies.
AB  - BACKGROUND: Traditional methods of educating residents and medical students using
      lectures and bedside teaching are no longer sufficient. Today's generation of
      trainees grew up in a multimedia environment, learning on the World Wide Web
      instead of reading books. It is unreasonable to expect the educational model
      developed 50 years ago to be able to adequately train the medical students and
      residents of today. One area that is difficult to teach is the diagnosis and
      management of the critically ill patient, specifically cardiac emergencies and
      cardiac arrest. RATIONALE: In the management of a patient in cardiac arrest, it
      is sometimes the least experienced provider giving chest compressions, intubating
      the patient, and running the code during the most crucial moment in that
      patient's life. METHODS: Patient simulation has emerged as an educational tool
      that allows the learner to practice patient care, away from the bedside, in a
      controlled and safe environment, giving the learner the opportunity to practice
      the educational principles of deliberate practice and self-reflection. We
      performed a qualitative literature review of the uses of simulators in medical
      training with a focus on their current and potential applications in cardiac
      emergencies.

PMID- 19384656
TI  - Syncope: experience at a tertiary care hospital in Karachi, Pakistan.
AB  - INTRODUCTION: Our aim was to determine the characteristics of patients presenting
      with syncope at a tertiary care hospital in Karachi, Pakistan. METHODS: A review
      of medical records was conducted retrospectively at the Department of Medicine,
      Aga Khan University Hospital, Karachi. Patients aged 16 and above, admitted from
      January 2000 to December 2005 with the diagnosis of syncope made by the attending
      physician were included. RESULTS: A total of 269 patients were included (75%
      males, mean age: 57.4 years). Neurogenic (vasovagal) syncope was the most common
      cause (47%), followed by cardiogenic syncope (18%) and orthostatic syncope (9%).
      A total of 24% were discharged undiagnosed. Twenty patients (7.4%) did not have
      any prodrome. Common prodromal symptoms included dizziness (61%), sweating (25%),
      palpitations (19%), nausea/vomiting (19%) and visual symptoms (17%). The
      distribution of symptoms according to cause of syncope revealed only
      breathlessness to be significantly associated with cardiogenic syncope (p =
      0.002). Most patients with cardiogenic syncope were aged above 40 (98%, p <
      0.001), had coronary artery disease (72%, p < 0.001) and abnormal
      electrocardiogram at presentation (92%, p < 0.001). CONCLUSION: Despite
      differences in burden of diseases, our findings were similar to those of
      published syncope literature. Further studies are needed to develop a protocol to
      expedite the evaluation and limit the work-up and admission in low-risk patients.

PMID- 19384657
TI  - Predicting observation unit treatment failures in patients with skin and soft
      tissue infections.
AB  - BACKGROUND: Skin and soft tissue infections are a common admission diagnosis to
      emergency department (ED) observation units (OU). Little is known about which
      patients fail OU treatment. AIMS: This study evaluates clinical factors of skin
      or soft tissue infections associated with further inpatient treatment after OU
      treatment failure. METHODS: A structured retrospective cohort study of
      consecutive adults treated for abscess or cellulitis in our OU from April 2005 to
      February 2006 was performed. Records were identified using ICD-9 codes and were
      abstracted by two trained abstractors using a structured data collection form.
      Significant variables on univariate analysis P < 0.1 were entered into a
      multivariate logistic regression. RESULTS: A total of 183 patient charts were
      reviewed. Four patients with a non-infectious diagnosis were excluded, leaving
      179 patients. The median age was 41 (interquartile range: 20-74). Following
      observation treatment, 38% of patients required admission. The following
      variables were evaluated for association with failure to discharge home:
      intravenous drug use, gender, a positive community-acquired methicillin-resistant
      Staphylococcus aureus culture, age, presence of medical insurance, drainage of an
      abscess in the ED, diabetes and a white blood cell count (WBC) greater than
      15,000. Following multivariate analysis only female gender odds ratio (OR) 2.33
      [95% confidence interval (CI): 1.06-5.15] and WBC greater than 15,000 OR 4.06
      (95% CI: 1.53-10.74) were significantly associated with failure to discharge.
      CONCLUSIONS: Among OU patients treated for skin and soft tissue infections, women
      were twice as likely to require hospitalization and patients with a WBC > 15,000
      on presentation to the ED, regardless of gender, were 4 times more likely to
      require hospitalization.

PMID- 19384658
TI  - Risk stratification of patients in an emergency department chest pain unit:
      prognostic value of exercise treadmill testing using the Duke score.
AB  - BACKGROUND: Exercise treadmill testing (ETT) has been standard for evaluating
      outpatients at risk for cardiovascular events. Few studies have demonstrated its
      prognostic usefulness in emergency department chest pain units or have used the
      Duke score [(exercise duration in minutes) - (5 x ST-segment deviation in
      millimeters) - (4 x treadmill angina index)] to grade its performance. AIMS: Our
      objective was to assess the usefulness of this score in a chest pain unit to
      predict cardiovascular events. METHODS: From November 2000 to October 2001, we
      retrospectively studied consecutive patients in the chest pain unit. Those
      undergoing ETT were stratified into "low" (Duke score > or = 5) and
      "moderate/high" risk groups (< 5). Cardiovascular events defined as death,
      myocardial infarction > 24 h after presentation, revascularization, acute
      congestive heart failure, stroke or arrhythmia were identified within 1 year
      after presentation. Differences in risk of having a cardiovascular event among
      low-risk and moderate/high-risk groups are presented. RESULTS: During the study
      period, 1,048 patients entered the chest pain unit; 800 met inclusion criteria.
      Of these, 599 received ETT and 201 had contraindications or a positive finding in
      the chest pain unit protocol before ETT. Cardiovascular event rates were 0.7%
      (3/454), 15.2% (22/145) and 14.9% (30/201) after 1 month of follow-up for low
      risk, moderate/high-risk and no-ETT groups, respectively. CONCLUSIONS: According
      to the Duke score, the low-risk group developed minimal cardiovascular events
      compared with the moderate/high-risk group. The Duke score appears effective for
      risk stratification of chest pain patients in chest pain units.

PMID- 19384659
TI  - Seizure visits in US emergency departments: epidemiology and potential
      disparities in care.
AB  - INTRODUCTION: While epilepsy is a well-characterized disease, the majority of
      emergency department (ED) visits for "seizure" involve patients without known
      epilepsy. The epidemiology of seizure presentations and national patterns of
      management are unclear. The aim of this investigation was to characterize ED
      visits for seizure in a large representative US sample and investigate any
      potential impact of race or ethnicity on management. METHODS: Seizure visits from
      the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 1993 to 2003
      were analysed. Demographic factors associated with presentation, neuroimaging and
      hospital admission in the USA were analysed using controlled multivariate
      logistic regression. RESULTS: Seizure accounts for 1 million ED visits annually
      [95% confidence interval (CI): 926,000-1,040,000], or 1% of all ED visits in the
      USA. Visits were most common among infants, at 8.0 per 1,000 population (95% CI:
      6.0-10.0), and children aged 1-5 years (7.4; 95% CI: 6.4-8.4). Seizure was more
      likely among those with alcohol-related visits [odds ratio (OR): 3.2; 95% CI: 2.7
      3.9], males (OR: 1.4; 95% CI: 1.3-1.5) and Blacks (OR: 1.4; 95% CI: 1.3-1.6).
      Neuroimaging was used less in Blacks than Whites (OR: 0.6; 95% CI: 0.4-0.8) and
      less in Hispanics than non-Hispanics (OR: 0.6; 95% CI: 0.4-0.9). Neuroimaging was
      used less among patients with Medicare (OR: 0.4; 95% CI: 0.2-0.6) or Medicaid
      (OR: 0.5; 95% CI: 0.4-0.7) vs private insurance and less in proprietary
      hospitals. Hospital admission was less likely for Blacks vs Whites (OR: 0.6; 95%
      CI: 0.4-0.8). CONCLUSION: Seizures account for 1% of ED visits (1 million
      annually). Seizure accounts for higher proportions of ED visits among infants and
      toddlers, males and Blacks. Racial/ethnic disparities in neuroimaging and
      hospital admission merit further investigation.

PMID- 19384660
TI  - The difficult airway in the emergency department.
AB  - BACKGROUND: The patient with difficult airways is a common challenge for
      emergency physicians. AIMS: Our goal was to study the reasons for difficult
      airways in the emergency department. METHODS: We performed a prospective
      observational study of patients requiring advanced airway management from 1
      January 2000 to 31 December 2006. RESULTS: There were 2,343 patients who received
      advanced airway management of which 93 (4.0%) were deemed difficult. The main
      diagnoses were cardiac arrest (28), trauma (27) and congestive heart failure
      (10). The main reasons for the difficult airways were attributed to an anterior
      larynx (38, 40.9%), neck immobility (22, 23.7%) as well as the presence of
      secretions and blood (14, 15.1%). The mean number of attempts at intubation was
      3.6 versus 1.2 for all cases. The mortality rate of 40.5% among patients with
      difficult airways was not different from that of all patients who had airway
      management (41%). There were seven (0.3%) failed airways. Anaesthetists performed
      21 (22.6%) of the rescue airways while surgeons performed 5 (5.4%). Of the rescue
      strategies performed, 24 were through the use of the bougie, 3 by
      cricothyroidotomy, 4 by tracheostomy, 6 with the GlideScope and 3 with the
      laryngeal mask airway. The rest the airways were secured by tracheal intubation
      using the laryngoscope. CONCLUSIONS: Emergency physicians manage most of the
      difficult airways successfully (68.8%). However, the success rate can be further
      improved through the more frequent use of the bougie or other rescue device. A
      possible suggestion would be for the emergency physician to use the bougie after
      the second or third attempt at direct orotracheal intubation.

PMID- 19384661
TI  - Measuring access to emergency obstetric care in rural Zambia.
AB  - BACKGROUND: Global health experts identify emergency obstetric care (EmOC) as the
      most important intervention to improve maternal survival in low- and middle
      income countries. In Zambia, 1 in 27 women will die of maternal causes, yet the
      level of availability of EmOC is not known at the provincial level. AIMS: Our
      goal was to develop a tool to measure the availability of EmOC in rural Zambia in
      order to estimate pregnant women's access to this life-saving intervention.
      METHODS: We created an instrument for determining the availability of EmOC based
      on the supplies and medicines in stock at health facilities as well as the skill
      level of health workers. We then surveyed a random sample of 35 health centres in
      the Central Province of Zambia using our novel instrument. RESULTS: We graded
      health centres based on their ability to provide the six basic functions of EmOC:
      administering parenteral antibiotics, administering parenteral oxytocics,
      administering parenteral anticonvulsants, performing manual removal of the
      placenta, removing retained products of conception and performing assisted
      vaginal delivery. Of the 29 health centres providing delivery care, 65% (19) were
      graded as level 1 or 2, 28% (8) as level 3 or 4 and 7% (2) as level 5. No health
      centre received a grade of level 6. CONCLUSION: The availability of EmOC in the
      Central Province of Zambia is extremely limited; the majority of health centres
      provide only one or two basic functions of EmOC, and no health centres perform
      all six functions. Our grading system allows for inter- and intra-country
      comparisons by providing a systematic process for monitoring access to EmOC in
      rural, low-income countries similar to Zambia.

PMID- 19384662
TI  - Clinical research 101: why should you care?

PMID- 19384663
TI  - Tetanus antibody protection among HIV-infected US-born patients and immigrants.
AB  - INTRODUCTION: Public health initiatives to immunize children and adults have
      effectively reduced the number of tetanus cases in the USA. However, in the Third
      National Health and Nutrition Examination Survey (NHANES III), immigrants from
      Mexico had a 67% nonprotective anti-tetanus antibody (ATA) level. Less work has
      been conducted among other vulnerable populations such as human immunodeficiency
      virus (HIV)-infected patients. The objective of this study was to measure ATA
      levels among the HIV immigrant population compared with US-born HIV-infected
      patients. METHODS: A convenience sample of 158 HIV-infected individuals was
      recruited to determine the levels of ATA. A nonprotective level of ATA was
      defined as below 0.15 IU/ml. RESULTS: Among the HIV-infected patients, 72%
      (114/158) were born in the USA. A total of 17% (27/158) lacked protective levels
      of ATA. A total of 6.1% (7/114) of those born in the USA lacked protection,
      compared to 45% (20/44) born outside the USA (p < 0.0001). CONCLUSION: The
      results illustrate that the country of birth is an important predictor of ATA
      protection, even among HIV-infected patients.

PMID- 19384664
TI  - Intubation practice patterns in Tuscan emergency departments.
AB  - INTRODUCTION: Intubation is one of the most important life-saving procedures
      performed by emergency physicians (EPs). There is variation in practice when
      different countries are compared. METHODS: A written questionnaire on intubation
      practices was administered to a group of Italian doctors practicing in Tuscany
      during the examination period of a year-long course in emergency medicine.
      RESULTS: The survey was administered to 153 participants. Of these, 143 (93.4%)
      returned a complete survey. In the sub-group of physicians who work in the
      emergency department (ED), 73.6% report intubating patients. Of those that
      intubate patients, 92.3% use some sort of sedation, and 49.3% use paralytics.
      While direct visualization of the cords for intubation and auscultation of breath
      sounds after intubation are almost universal (97% and 100%, respectively), only
      11.9% use colorimetric CO2 detectors for confirmation of intubation. After
      intubation 58.2% commonly place a nasogastric tube and 50.7% obtain a post
      intubation chest radiograph. CONCLUSIONS: Practice patterns in the USA and
      Tuscany are different. RSI and post-intubation radiographs are the standard of
      care in EDs in the USA. This is not the case in Tuscany.

PMID- 19384665
TI  - Mortality after emergency department intubation.
AB  - INTRODUCTION: The purpose of this study is to identify the rate of emergency
      department (ED) intubation and the mortality associated with ED intubation.
      METHODS: We conducted a retrospective chart review of all patients intubated in
      the ED between 1 January 2004 and 31 December 2004 at an urban level one trauma
      centre with approximately 50,000 ED visits annually. All ED intubations were
      identified and reviewed. Two investigators reviewed all charts and collected the
      following data: age, sex, and final disposition from hospital as well as reason
      for intubation. The main outcome measure was survival to hospital discharge.
      RESULTS: One hundred sixty-three intubations were reviewed. Of the total 163
      patients, 44 (27.0%) died prior to discharge from the hospital, 42 (25.8.%)
      patients were discharged to a skilled nursing facility (e.g. nursing home,
      rehabilitation and extended care facility) and 71 (43.6%) patients were
      discharged home. Dividing our cohort into trauma and non-trauma subgroups, 38/126
      (30.2%) of the non-trauma patients and 6/37 (16.2.%) of the trauma patients died.
      The mean age for all patients in our study group was 61.5 years, with trauma
      patients being younger than the non-trauma subgroup. The mean age for trauma
      patients was 50.1 while non-trauma patients had a mean age of 64.8. CONCLUSIONS:
      The mortality after an ED intubation in our study population was relatively high.
      Further studies need to confirm these findings and help identify predictors of
      mortality.

PMID- 19384666
TI  - A pilot study of the King LT supralaryngeal airway use in a rural Iowa EMS
      system.
AB  - INTRODUCTION: In 2003, the King Laryngeal Tube (LT) received FDA approval for US
      sales. Prehospital systems in urban setting have begun evaluating and adopting
      the LT for clinical airway management. However, it is not routinely approved by
      State EMS Boards for use by all prehospital providers. Given the LT's simple
      design there may be benefit to using this tool for airway management in all
      levels of prehospital providers. This pilot study reviews cases where the King LT
      was used in a rural Iowa county EMS system. METHODS: In 2006, the Iowa Department
      of Public Health / Bureau of EMS approved a 12 month pilot evaluating the King LT
      by all levels of EMS providers in a rural county EMS system. Following a didactic
      and competency training session on using the King LT, the providers were
      instructed to continue airway management per usual protocol but were allowed to
      use the King LT as a first line airway tool if they felt indicated. Successful
      placement of airway devices used were determined by colourimetric end-tidal CO2,
      chest auscultation and rise as well as vital sign and skin colour improvement.
      Review of the data was approved by the University of Iowa Institution Review
      Board (IRB). RESULTS: During the 12-month pilot period, the King LT was used in
      13 patients with a mean age of 60.7 years (24-81). All patients had
      cardiopulmonary or traumatic arrest. The King LT was successfully placed on the
      first attempt in all but one case. The King LT was placed following endotracheal
      intubation failure in 6/13 (46.1%) cases and in 3/13 (23.1%) of cases of
      Combitube attempt / failure. CONCLUSIONS: This small pilot project emphasizes the
      need for additional rapid airway management tools given the demonstrated ETI
      failures. The authors believe the King LT has significant potential to impact
      prehospital airway management as a primary airway device or backup to other
      failed strategies. Further study is necessary to evaluate the LT's efficacy
      compared to current strategies.

PMID- 19384667
TI  - ED chief complaint categories for a medical student curriculum.
AB  - BACKGROUND: It is important to stimulate the interest of all medical students in
      emergency medicine to further its growth nationally and internationally. Students
      focused on other specialties can benefit from exposure to the more common, less
      acute problems seen in the emergency department (ED). AIMS: We developed a
      categorization system for chief complaints (CC) in an academic ED fast track (FT)
      area, so that a curriculum based upon actual CC and clinical experience could be
      designed for learners. METHODS: Primary (first) FTCCs were obtained from the ED
      electronic record of an academic medical center from 1 to 10 July 2006 and 1 to
      10 February 2007. Category definitions were developed, and CCs were collapsed
      into clinically coherent groups. Inter-rater reliability was assessed, and CC
      categories were compared for the two study periods. The study was exempted by the
      University Institutional Review Board. RESULTS: In the July data set, 493 CCs
      were placed into 8 categories which captured 96.3% of CCs: pain 32.3%, injury
      26.6%, infection 15%, psychiatric 8.1%, miscellaneous 6.1% (those with a
      frequency of </= 2%), nurse only visit 5.5%, eye 4.3% and rash 2.2%. The weighted
      kappa for CC categorization between two observers was 0.8980 (95% confidence
      interval: 0.8638-0.9322). In the February data set, refinements with 454 CCs
      resulted in categorization of 96.9% of the CCs into the same 8 categories with 53
      subcategories. The distribution of the major categories was similar in July and
      February (p = 0.13). CONCLUSIONS: The FTCC categorization was valid and reliable
      and can guide curriculum development for learners in an academic setting.

PMID- 19384668
TI  - Pneumoencephalus after one missed step.

PMID- 19384669
TI  - Testicular torsion-a common surgical emergency.

PMID- 19384670
TI  - Pott's paresis presentation in the emergency department.

PMID- 19384671
TI  - High-pressure water injection injury.

PMID- 19384672
TI  - Septic thrombophlebitis with acute osteomyelitis in adolescent children: a report
      of two cases and review of the literature.
AB  - The triad of acute osteomyelitis, deep venous thrombophlebitis, and septic
      pulmonary embolism is a rare, but life-threatening syndrome in children that
      requires prompt recognition and treatment. We report two cases of acute
      osteomyelitis complicated by septic thrombophlebitis and pulmonary emboli. Both
      patients required operative drainage to remove the septic focus. Recognition of
      any one component of the triad should prompt a search for the other associated
      disorders. Aggressive management with early antibiotic administration,
      anticoagulation, and surgical debridement can be life saving.

PMID- 19384673
TI  - Cost-effectiveness analysis of solifenacin flexible dosing in patients with
      overactive bladder symptoms in four Nordic countries.
AB  - OBJECTIVE: The purpose of the present analysis was to analyze and compare the
      cost-effectiveness of solifenacin flexible dosing (5-10 mg) with tolterodine 4 mg
      sustained release (SR) or placebo (assumed to be comparable to no treatment) for
      patients with overactive bladder (OAB) symptoms. DESIGN: A decision-analytic
      model was constructed. METHODS: Costs and effects were evaluated for the three
      treatment options in a one-year timeframe. Costs included were treatment costs,
      cost of pad use, and patients productivity loss based on data from the Nordic
      countries. SAMPLE: Results from two randomized controlled trials were used as
      input data in the cost-effectiveness analysis. MAIN OUTCOME MEASURES: Quality
      adjusted life years and incremental cost-effectiveness ratio. RESULTS:
      Solifenacin flexible dosing was more effective with respect to reducing OAB
      symptoms compared to both placebo and tolterodine 4 mg. Treatment with both
      solifenacin and tolterodine was more costly compared to placebo, but treatment
      with solifenacin was a less costly alternative compared to tolterodine 4 mg SR.
      Sensitivity analyses revealed that the conclusions were robust. CONCLUSION:
      Solifenacin flexible dosing was a cost-effective treatment alternative compared
      to tolterodine 4 mg SR.

PMID- 19384674
TI  - Intramural left atrial hematoma: a complication of primary coronary angioplasty
      inferior myocardial infarction.

PMID- 19384675
TI  - Digoxin for the treatment of chronic and acute heart failure syndromes.
AB  - Digitalis preparations have been used for centuries. Digoxin is an agent that is
      readily available, can be administered acutely and long-term, intravenously or
      orally, is safe and may be beneficial in both acute and chronic heart failure
      (HF). It may be an ideal drug for the treatment of acute heart failure syndromes
      and warrants further investigation in large clinical trials. The role of digoxin
      in acute and chronic HF was discussed at the 2008 European Society of Cardiology
      Working Group on Acute Cardiac Care Meeting held in Versailles, France from 25-28
      October 2008. This report represents a summary of the presentation at this
      meeting.

PMID- 19384676
TI  - ECG-based wireless home infant apnoea monitor.
AB  - A safe and wireless system for infant apnoea monitoring and treatment is
      proposed. It consists of two separate modules that detect apnoea based on a
      microcontroller processing and transmitting signals to the remote unit using
      wireless communication arrangement. Depending on the ECG signal, this system
      records the infant's heart and respiratory rates. Recognition of the consecutive
      QRS complexes within the ECG signal helps in calculating these vitals. Abnormal
      breathing rate or heart rate (apnoea) triggers both an alarm system on the remote
      unit to inform parents of this abnormality and a treatment device that stimulates
      the infant to breathe using vibration transducer. Different ECG signals from the
      MIT-Physionet database were used to test the prototype. The system successfully
      extracted, analysed and transmitted required vitals and decisions to the
      receiving unit. Finally, the system was bench tested on 25 adult volunteers and
      12 young children; voluntarily cessations of breathing were detected successfully
      for all subjects.

PMID- 19384677
TI  - 17beta-estradiol induces the proliferation of the in vitro cultured human
      urothelium.
AB  - OBJECTIVE: The genitourinary tract is considered to be a target for the actions
      of sex steroid hormones. Decreased ovarian function and lack of estrogen after
      menopause are associated with lower genitourinary tract symptoms as well as
      bladder dysfunctions such as incontinence. Estrogen may also affect urothelial
      cells. The estrogen receptors (ERs) are found in the mucosa of the urinary tract.
      The purpose of this study was to culture human urothelial cells (HUCs)
      originating from urothelial tissue biopsies and to use them as a reproducible
      test platform to evaluate the effect of 17beta-estradiol (E2). MATERIAL AND
      METHODS: Urothelial tissue biopsies were obtained from 95 patients undergoing
      gynaecological open surgery for urinary incontinence, paediatric vesicoureteral
      reflux or transurethral resection of the prostate (TURP) for benign prostatic
      hyperplasia. HUCs originating from biopsies were cultured in vitro in the absence
      or in the presence of 0.1 nmol, 0.01 micromol and 1 micromol of E2. ER expression
      of the cultured HUCs was examined by Western analysis and immunofluorescence
      microscopy, which was also used for HUC characterization. The effect of E2 in the
      proliferation of the HUCs was determined by tetrazolium salt 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)-assay. RESULTS: HUCs
      were cultured successfully in four to six passages but there was variation
      between samples. The cultured cells showed expression of beta(4)-integrin, E
      cadherin and cytokeratins 7, 8, 9 and 19, indicating the epithelial origin of the
      cells. Both types of ERs, ERalpha and ERbeta, were found in the in vitro cultured
      HUCs. E2 treatment of HUCs did not affect remarkably the expression of ERalpha
      but cell proliferation was induced. However, no concentration-dependent effect
      was seen. CONCLUSIONS: This study indicates that HUCs originating from small
      tissue biopsies can be cultured in several passages in vitro and could have
      potential in repairing or restoring urinary tract tissue by tissue engineering
      therapy. HUCs serve as a good in vitro test platform, as shown by analysing E2
      treated HUCs. E2 induced the proliferation of cultured HUCs even though
      concentration dependency was not observed. The findings of this study may have
      relevance in determining the mechanisms of estrogen therapy in postmenopausal
      urinary tract symptoms and in the future development of tissue engineering
      technology.

PMID- 19384678
TI  - Trazodone generates m-CPP: in 2008 risks from m-CPP might outweigh benefits of
      trazodone.
AB  - Since deleterious effects of m-CPP, the primary catabolic metabolite of
      trazodone, were last reviewed 2 years ago, research data continue to accrue
      showing that clinically significant levels of m-CPP (a) are generated in patients
      using trazodone for sleep and (b) are present 24 h a day and (c) have potentially
      serious ill effects. This commentary argues that the documented potential for
      harm and multiple risks of m-CPP outweigh potential benefits of trazodone, given
      the development and marketing of many safer alternatives since trazodone's
      introduction in the 1980s.

PMID- 19384679
TI  - Prenatal mercury exposure and postnatal outcome: clinical case report and
      analysis.
AB  - INTRODUCTION: It is well known that vapor emitted from metallic mercury is a
      potent neurotoxic agent, but little toxicological information on liquid metallic
      mercury itself is available, especially with respect to developmental
      neurotoxicity. We were unable to find any cases of parental metallic mercury
      administration that reveal its effect on embryogenesis and human development.
      CASE REPORT: Young woman who, following a suicide attempt through the intravenous
      injection of liquid mercury, developed extremely high blood and urine mercury
      levels but was able to become pregnant and deliver an apparently mature and
      healthy infant. ANALYSIS: To our knowledge, there were no similar cases reported
      in the literature. Therefore, we chose to perform a detailed analysis of this
      unique clinical case. We report levels of mercury in maternal, umbilical cord,
      and infant blood, in samples of breast milk and placental tissues. Despite high
      levels of mercury in blood and urine samples, no immediate adverse heath effects
      were observed in either mother or infant. This case may shed a new light and
      information on the toxicology of mercury.

PMID- 19384680
TI  - Beryllium and lung cancer: a weight of evidence evaluation of the toxicological
      and epidemiological literature.
AB  - The potential carcinogenicity of beryllium has been a topic of study since the
      mid-1940s. Since then, numerous scientific and regulatory bodies have assigned
      beryllium to various categories with respect to its carcinogenicity. Past
      epidemiologic and animal studies, however, have been marked with notable
      methodological shortcomings. Because it has been about 16 yr since IARC evaluated
      beryllium and approximately 50 relevant papers on the topic have been published
      since that time, we conducted a weight-of-evidence analysis of the historical as
      well as recent animal and human literature. We also assessed whether recently
      published studies improved upon methodological shortcomings or shed light upon
      uncertainties in prior studies. Thirty-three animal studies, principally designed
      to evaluate the cancer hazard or related mechanisms, and seventeen epidemiologic
      studies were considered in this assessment. Based on this analysis, the evidence
      for carcinogenicity of beryllium is not as clear as suggested by previous
      evaluations, because of the inadequacy of the available smoking history
      information, the lack of well-characterized historical occupational exposures and
      shortcomings in the animal studies. We concluded that the increase in potential
      risk of lung cancer was observed among those exposed to very high levels of
      beryllium and that beryllium's carcinogenic potential in humans at exposure
      levels that exist in modern industrial settings should be considered either
      inadequate or marginally suggestive.

PMID- 19384681
TI  - Internally displaced human resources for health: villager health worker
      partnerships to scale up a malaria control programme in active conflict areas of
      eastern Burma.
AB  - Approaches to expand malaria control interventions in areas of active conflict
      are urgently needed. Despite international agreement regarding the imperative to
      control malaria in eastern Burma, there are currently no large-scale
      international malaria programmes operating in areas of active conflict. A local
      ethnic health department demonstrated that village health workers are capable of
      implementing malaria control interventions among internally displaced persons
      (IDPs). This paper describes how these internally displaced villagers facilitated
      rapid expansion of the programme. Clinic health workers received training in
      malaria diagnosis and treatment, vector control and education at training sites
      along the border. After returning to programme areas inside Burma, they trained
      villagers to perform an increasingly comprehensive set of interventions. This
      iterative training strategy to increase human resources for health permitted the
      programme to expand from 3000 IDPs in 2003 to nearly 40,000 in 2008. It was
      concluded that IDPs are capable of delivering essential malaria control
      interventions in areas of active conflict in eastern Burma. In addition, health
      workers in this area have the capacity to train community members to take on
      implementation of such interventions. This iterative strategy may provide a model
      to improve access to care in this population and in other conflict settings.

PMID- 19384682
TI  - Pleiotrophin inhibits hippocampal long-term potentiation: a role of pleiotrophin
      in learning and memory.
AB  - Pleiotrophin (PTN) is a growth factor that has been shown to be involved in
      hippocampal synaptic plasticity and learning. To further understand the
      involvement of PTN in memory processes, we performed in vitro
      electrophysiological studies in PTN-stimulated CA1 from rat hippocampal slices
      combined with the behavioural testing of PTN deficient (PTN - / - ) mice. We
      found that PTN inhibited hippocampal long-term potentiation (LTP) induced by high
      frequency stimulation (HFS) consisted in three trains of 100 Hz separated by 20
      s. To test the possibility that PTN might be involved in behavioural memory
      processes, we tested the learning behaviour of PTN - / - mice using the Y-maze
      test. We did not observe significant differences in recognition memory between
      PTN - / - and Wild Type (WT) mice when a 30 min-interval intertrial (ITI) was
      used in the Y-maze test. However, whereas WT mice showed disruption of
      recognition memory using a 60 min-ITI, PTN - / - mice maintained the recognition
      memory. The data demonstrate that PTN inhibits hippocampal LTP in vitro and might
      play a role in memory processes in vivo.

PMID- 19384683
TI  - Role of the C-terminal linear region of EGF-like growth factors in ErbB
      specificity.
AB  - The epidermal growth factor (EGF)-like growth factors bind their ErbB receptors
      in a highly selective manner. Recently, we have shown that the sequence YYDLL in
      the C-terminal linear region is compatible with binding to all ligand-binding
      ErbB receptors. In the present study, we show that introduction of the YYDLL
      sequence into the ErbB1 specific ligands EGF and transforming growth factor-alpha
      (TGFalpha) broadened their receptor specificity towards ErbB4. Upon introduction
      of the YYDLL sequence into epiregulin, which by itself binds ErbB1 and ErbB4 but
      not ErbB3, its binding specificity was broadened to ErbB3, concomitant with
      enhanced affinity for ErbB4. Introduction of the YYDLL sequence into NRG1beta
      resulted in a 10-fold increase in affinity for ErbB3, without affecting its
      receptor specificity. Remarkably, the strongly enhanced affinity for ErbB3
      negatively influenced their mitogenic activity towards cells coexpressing ErbB2
      and ErbB3. These observations are discussed in terms of the optimised ErbB
      affinity, selectivity and mitogenic potential that have taken place during
      evolution.

PMID- 19384684
TI  - Journal of Biopharmaceutical Statistics. From the editors.

PMID- 19384685
TI  - Theoretical and practical application of traditional and accelerated titration
      Phase I clinical trial designs: the Wayne State University experience.
AB  - The traditional and accelerated titration (AT) designs are two frequently
      utilized Phase I clinical trial designs. Although each design has theoretical
      advantages and disadvantages, a summary of the practical application of these
      theories has not been reported. We report our center's experience in evaluating
      novel agents using both types of Phase I trial designs over a 13-year period.
      Results from nine Phase I clinical trials of multiple cytotoxic agents conducted
      at Wayne State University/Karmanos Cancer Institute in Detroit, MI, and published
      from 1995-2005 were analyzed for this report. Parameters analyzed included the
      number of patients, the number of dose levels, the total time to completion of
      the study, and adverse events. The mean number of patients treated on four Phase
      I trials using the traditional Phase I trial design was 34 compared to a mean of
      23.8 patients treated on five Phase I trials using the AT schema. The mean number
      of dose levels in patients treated using the traditional Phase I trial design was
      8.8 (range 7-11) compared to a mean of 10.6 (range 7-15) dose levels using the AT
      design. The mean length of study time (25-26 months) was similar in both trial
      designs. The theoretical advantages and disadvantages of both Phase I trial
      designs did not readily emerge in their actual application in clinical trials
      conducted at our institution.

PMID- 19384686
TI  - Optimal cost-effective designs of Phase II proof of concept trials and associated
      go-no go decisions.
AB  - This manuscript discusses optimal cost-effective designs for Phase II proof of
      concept (PoC) trials. Unlike a confirmatory registration trial, a PoC trial is
      exploratory in nature, and sponsors of such trials have the liberty to choose the
      type I error rate and the power. The decision is largely driven by the perceived
      probability of having a truly active treatment per patient exposure (a surrogate
      measure to development cost), which is naturally captured in an efficiency score
      to be defined in this manuscript. Optimization of the score function leads to
      type I error rate and power (and therefore sample size) for the trial that is
      most cost-effective. This in turn leads to cost-effective go-no go criteria for
      development decisions. The idea is applied to derive optimal trial-level, program
      level, and franchise-level design strategies. The study is not meant to provide
      any general conclusion because the settings used are largely simplified for
      illustrative purposes. However, through the examples provided herein, a reader
      should be able to gain useful insight into these design problems and apply them
      to the design of their own PoC trials.

PMID- 19384687
TI  - Continual reassessment method vs. traditional empirically based design:
      modifications motivated by Phase I trials in pediatric oncology by the Pediatric
      Brain Tumor Consortium.
AB  - In this article we provide additional support for the use of a model-based design
      in pediatric Phase I trials and present our modifications to the continual
      reassessment method (CRM), which were largely motivated by specific challenges we
      encountered in the context of the Pediatric Brain Tumor Consortium trials. We
      also summarize the results of our extensive simulations studying the operating
      characteristics of our modified approach and contrasting it to the empirically
      based traditional method (TM). Compared to the TM, our simulations indicate that
      the modified version of CRM is more accurate, exposes fewer patients to
      potentially toxic doses, and tends to require fewer patients. Further, the CRM
      based MTD has a consistent definition across trials, which is important,
      especially in a consortium setting where multiple agents are being tested in
      studies that are often running simultaneously and accruing from the same patient
      population.

PMID- 19384688
TI  - Between-arm comparisons in randomized Phase II trials.
AB  - In a Phase II trial, we may randomize patients to multiple arms of experimental
      therapies and evaluate their efficacy to determine if any of them is worthy of a
      large scale Phase III trial. Usually the primary objective of such a study is to
      identify experimental therapies that are efficacious compared to a historical
      control. Each arm is independently evaluated using a standard design a for single
      arm Phase II trial, e.g., Simon's optimal or minimax design. When more than one
      arm is accepted through such a randomized trial, we may want to select the
      winner(s) among them. There are methods for between-arm comparisons in the
      literature, but most of them have drawbacks. They have a large false selection
      (type I error) probability when the competing arms have a small difference in
      efficacy, or the statistical tests used in the selection procedure do not
      properly reflect the small sample sizes and multi-stage design of the trials. In
      this paper, we propose between-arm comparison methods for selection in randomized
      Phase II trials addressing these issues.

PMID- 19384689
TI  - A Bayesian case study in oncology Phase I combination dose-finding using logistic
      regression with covariates.
AB  - A Bayesian approach to finding the maximum tolerated dose (MTD) is presented. The
      approach is flexible, allowing inclusion of covariates, and enables transparent
      dose recommendations based on comprehensive inferential summaries on the
      probability of dose-limiting toxicities (DLT). A case study is presented for a
      Phase I combination of two oncology drugs, nilotinib and imatinib. Data obtained
      and decisions made during the study are described. Final determination of the MTD
      pair is outlined, along with discussion regarding the use and interpretability of
      within- and end-of-study data.

PMID- 19384690
TI  - Optimal two-stage randomized multinomial designs for Phase II oncology trials.
AB  - A new two-stage design is proposed that is suitable for early detection of the
      anticancer activity of experimental therapies in Phase II oncology trials. The
      endpoints of interest are response rate and early progression rate. The
      anticancer activity is defined by a positive signal in one endpoint and a non
      negative signal in the other endpoint. The two endpoints are modeled by the
      multinomial distribution. The design is optimal in that it minimizes the patient
      exposure when the experimental therapies are inactive. The design parameters are
      found by a grid searching algorithm under type I and type II error rate
      constraints. Examples of the design are also presented in this paper.

PMID- 19384692
TI  - Design issues in dose-finding Phase I trials for combinations of two agents.
AB  - Combination therapy of two antitumor agents may provide treatment additivity or
      synergy. Phase I trials for combination therapy search for the maximum tolerated
      dose (MTD) for combined agents. The conventional approach is to preselect an
      escalation path, usually increasing the dose of one agent and then another, and
      to use the standard 3 + 3 design. However, this procedure may miss the optimum
      dose combination, prolong the time it takes, and increase the number of patients
      necessary to reach the MTD. In this study, we present strategies for a
      comprehensive search for MTD for a two-agent combination therapy. We evaluate
      algorithms based on two-stage and three-stage design as well as variations in
      cohort size. A two-dimensional isotonic estimation method for toxicity rate is
      provided. We use simulation methods to compare 2 + 1 + 3 vs. 3 + 3 cohort sizes.
      We conclude that the comprehensive search proposed in our study can be more
      practical and efficient in identifying the MTD in combination-therapy of two
      agents.

PMID- 19384691
TI  - Selecting promising treatments in randomized Phase II cancer trials with an
      active control.
AB  - The primary objective of Phase II cancer trials is to evaluate the potential
      efficacy of a new regimen in terms of its antitumor activity in a given type of
      cancer. Due to advances in oncology therapeutics and heterogeneity in the patient
      population, such evaluation can be interpreted objectively only in the presence
      of a prospective control group of an active standard treatment. This paper deals
      with the design problem of Phase II selection trials in which several
      experimental regimens are compared to an active control, with an objective to
      identify an experimental arm that is more effective than the control or to
      declare futility if no such treatment exists. Conducting a multi-arm randomized
      selection trial is a useful strategy to prioritize experimental treatments for
      further testing when many candidates are available, but the sample size required
      in such a trial with an active control could raise feasibility concerns. In this
      study, we extend the sequential probability ratio test for normal observations to
      the multi-arm selection setting. The proposed methods, allowing frequent interim
      monitoring, offer high likelihood of early trial termination, and as such enhance
      enrollment feasibility. The termination and selection criteria have closed form
      solutions and are easy to compute with respect to any given set of error
      constraints. The proposed methods are applied to design a selection trial in
      which combinations of sorafenib and erlotinib are compared to a control group in
      patients with non-small-cell lung cancer using a continuous endpoint of change in
      tumor size. The operating characteristics of the proposed methods are compared to
      that of a single-stage design via simulations: The sample size requirement is
      reduced substantially and is feasible at an early stage of drug development.

PMID- 19384693
TI  - Design of Phase II cancer trials for evaluation of cytostatic/cytotoxic agents.
AB  - For experimental anticancer agents that may have both cytostatic and cytotoxic
      effects, assessment of response rates alone may not capture the full impact of
      the treatment. Oncologists are therefore interested in assessing both response
      and stable disease rates in early phase clinical trials of such therapies. We
      describe the design of a single-arm, Phase II clinical trial for the simultaneous
      evaluation of objective response and stable disease (lack of early tumor
      progression) rates using standard RECIST criteria. Demonstration of a
      sufficiently high rate for either of these endpoints will lead to rejection of
      the null hypothesis and a conclusion that the treatment warrants further study. A
      design is chosen that satisfies the desired type I error constraint and has
      sufficient statistical power at several selected points within the alternative
      hypothesis space using a restricted search algorithm. An early stopping rule for
      lack of efficacy is incorporated. The method is illustrated by the design of a
      Phase II clinical trial in head and neck cancer.

PMID- 19384694
TI  - Clinical trial designs for predictive biomarker validation: one size does not fit
      all.
AB  - Traditionally, anatomic staging systems have been used to provide predictions of
      individual patient outcome and, to a lesser extent, guide the choice of treatment
      in cancer patients. With targeted therapies, biomarkers have the potential for
      providing added value through an integrated approach to prediction using the
      genetic makeup of the tumor and the genotype of the patient for treatment
      selection and patient management. Specifically, biomarkers can aid in patient
      stratification (risk assessment), treatment response identification (surrogate
      markers), or differential diagnosis (identifying individuals who are likely to
      respond to specific drugs). In this study, we explore two major topics in
      relation to the design of clinical trials for predictive marker validation.
      First, we discuss the appropriateness of an enrichment (i.e., targeted) vs. an
      unselected design through case studies focusing on the clinical question(s) at
      hand, the strength of the preliminary evidence, and assay reproducibility.
      Second, we evaluate the efficiency (total number of events and sample size) of
      two unselected predictive marker designs for validation of a marker under a wide
      range of clinically relevant scenarios, exploring the impact of the prevalence of
      the marker and the hazard ratios for the treatment comparisons. The review and
      evaluation of these designs represents an essential step toward the goal of
      personalized medicine because we explicitly seek to explore and evaluate the
      methodology for the clinical validation of biomarker guided therapy.

PMID- 19384695
TI  - Some notable properties of the standard oncology Phase I design.
AB  - We identify three properties of the standard oncology Phase I trial design or 3 +
      3 design. We show that the standard design implicitly uses isotonic regression to
      estimate a maximum tolerated dose. We next illustrate the relationship between
      the standard design and a Bayesian design proposed by Ji et al. (2007). A slight
      modification to this Bayesian design, under a particular model specification,
      would assign treatments in a manner identical to the standard design. We finally
      present calculations revealing the behavior of the standard design in a worst
      case scenario and compare its behavior with other 3 + 3-like designs.

PMID- 19384696
TI  - Current issues in oncology drug development, with a focus on Phase II trials.
AB  - In this commentary we discuss several challenges that are of current relevance to
      the design of clinical trials in oncology. We argue that the compartmentalization
      of trials into the three standard phases, with non overlapping aims, is not
      necessary and in fact may slow the clinical development of agents. Combined Phase
      I/II trials and/or Phase I trials that at minimum collect efficacy data and more
      optimally include a preliminary measure of efficacy in dosing determination
      should be more widely utilized. Similarly, we posit that randomized Phase II
      trials should be used more frequently, as opposed to the traditional historical
      single arm Phase II trial that usually does not have a valid comparison group.
      The use of non binary endpoints is a simple modification that can improve the
      efficiency of early phase trials. The heterogeneity in scientific goals and
      contexts in early phase oncology trials is considerable, and the potential to
      improve the design to match these goals is great. We review these and other
      issues in the context of 5 manuscripts related to Phase II trials published in
      this volume. Our overall premise is that the potential benefits associated with
      the oncology clinical trial community moving away from the one size fits all
      paradigm of trial design are great, and that more flexible and efficient designs
      tailored to match the goals of each study are currently available and being used
      successfully.

PMID- 19384700
TI  - Attitudes of medical students to multiprofessional teaching sessions: are they
      time well spent?

PMID- 19384701
TI  - Tactile resonance sensors in medicine.
AB  - Tactile sensors in general are used for measuring the physical parameters
      associated with contact between sensor and object. Tactile resonance sensors in
      particular are based on the principle of measuring the frequency shift, Deltaf,
      defined as the difference between a freely vibrating sensor resonance frequency
      and the resonance frequency measured when the sensor makes contact to an object.
      Deltaf is therefore related to the acoustic impedance of the object and can be
      used to characterize its material properties. In medicine, tactile resonance
      sensor systems have been developed for the detection of cancer, human ovum
      fertility, eye pressure and oedema. In 1992 a Japanese research group published a
      paper presenting a unique phase shift circuit to facilitate resonance
      measurements. In this review we summarize the current state-of-the-art of tactile
      resonance sensors in medicine based on the phase shift circuit and discuss the
      relevance of the measured parameters for clinical diagnosis. Future trends and
      applications enabled by this technology are also predicted.

PMID- 19384702
TI  - Detecting early breast tumour by finite element thermal analysis.
AB  - Thermography has been proved to be an effective technique for indicating breast
      disease abnormalities or risks. However, the abnormalities might not express
      clearly due to various factors, such as when a small tumour is located in a deep
      region, or environmental influences that make breast disease difficult to find.
      This study aims to solve these problems for early detection of breast tumour. A
      three-dimensional breast model is presented to investigate the relationship
      between an embedded tumour and the surface temperature distribution. Then a
      subtraction technique is used to enhance the thermal signature of breast tumour.
      It was showed that the surface thermal characteristics of a small tumour even in
      a deep region could be found easily by this method. Furthermore, it was also
      found that the surface thermal characteristics of tumour obscured due to
      environmental cooling effect can be clearly displayed. The results are very
      useful for analysing breast thermograms.

PMID- 19384703
TI  - Assessing effects of PEEP and global expiratory lung volume on regional
      electrical impedance tomography.
AB  - OBJECTIVE: This study was performed to assess the value of electrical impedance
      tomography (EIT) as an indicator of tidal (V(T)) and end expiratory lung volume
      (EELV). METHODS: EIT measurements were performed in seven healthy piglets during
      constant tidal volume ventilation at incremental and decremental positive end
      expiratory pressure (PEEP) levels. Tidal impedance changes were calibrated to
      volume using V(T) calculated from flow at the airway opening. Simultaneously,
      calibrated respiratory inductive plethysmography was used to measure EELV
      changes, and used as a reference standard. RESULTS: EIT systematically
      underestimated both V(T) and EELV changes when EELV deviated from the level at
      which it was calibrated. Calculated over the entire pressure-volume curve, EIT
      systematically underestimated V(T) by 28 ml, with a precision from -16 to 72 ml.
      EELV was systemically underestimated by 406 ml, with a precision of -38 to 849
      ml. Nonlinear recruitment in the ventral regions of the lungs was the main cause
      of this underestimation. CONCLUSIONS: Tidal and end-expiratory changes in
      pulmonary impedance reflect corresponding changes in lung volume, but the
      increasing underestimation with increasing lung volume should be taken into
      account in the analysis of EIT data.

PMID- 19384704
TI  - Extraction of specific parameters for skin tumour classification.
AB  - In this paper, a methodological approach to the classification of tumour skin
      lesions in dermoscopy images is presented. Melanomas are the most malignant skin
      tumours. They grow in melanocytes, the cells responsible for pigmentation. This
      type of cancer is increasing rapidly; its related mortality rate is increasing
      more modestly, and inversely proportional to the thickness of the tumour. The
      mortality rate can be decreased by earlier detection of suspicious lesions and
      better prevention. Using skin tumour features such as colour, symmetry and border
      regularity, an attempt is made to determine if the skin tumour is a melanoma or a
      benign tumour. In this work, we are interested in extracting specific attributes
      which can be used for computer-aided diagnosis of melanoma, especially among
      general practitioners. In the first step, we eliminate surrounding hair in order
      to eliminate the residual noise. In the second step, an automatic segmentation is
      applied to the image of the skin tumour. This method reduces a colour image into
      an intensity image and approximately segments the image by intensity
      thresholding. Then, it refines the segmentation using the image edges, which are
      used to localize the boundary in that area of the skin. This step is essential to
      characterize the shape of the lesion and also to locate the tumour for analysis.
      Then, a sequences of transformations is applied to the image to measure a set of
      attributes (A: asymmetry, B: border, C: colour and D: diameter) which contain
      sufficient information to differentiate a melanoma from benign lesions. Finally,
      the various signs of specific lesion (ABCD) are provided to an artificial neural
      network to differentiate between malignant tumours and benign lesions.

PMID- 19384705
TI  - Time-frequency analysis of foetal heart sound signal for the prediction of
      prenatal anomalies.
AB  - Motion of the foetal heart gives rise to vibrations and sounds that can be
      acquired through the surface of the maternal abdominal wall. The process is
      called foetal phonocardiography (fPCG) and its study has shown to be a very
      useful mechanism to evaluate the wellbeing of the unborn. These signals exhibit
      innate rhythms and periodicity that are more readily expressed and appreciated in
      terms of frequency than time units. Time-frequency distribution shows the
      spectral composition of signal at a particular time instant, which is also known
      as a spectrogram. This work investigates the analysis of foetal heart sound using
      time frequency distribution generated by short-time Fourier transform (STFT). An
      innovative method is presented for foetal heart sound acquisition, processing and
      coloured spectral representation, which can be used in a portable foetal home
      monitoring system. The outcome of the work is a numerous spectral display
      produced by the system for varied real and simulated foetal heart sound signals.
      A comparative study of normal and abnormal heart sound is presented. The
      spectrograms exhibit noticeable morphological differences in terms of duration
      and spectral composition of the sounds. The study suggests that STFT based
      coloured spectrograms can become an important diagnostic tool, and it is expected
      that the presented work will facilitate the potential use of the method in
      prediction of the prenatal anomalies.

PMID- 19384706
TI  - A novel active contour model for serial image segmentation.
AB  - A novel method for the segmentation of serial images is proposed. In the
      presented framework, the driving force acts as the attracting term to propel the
      evolving curve towards the object boundaries, and the adaptive term changes the
      sign of driving force accordingly. Therefore, the evolving curves can arrive at
      the desired direction without a requirement for the initial curve to be strictly
      inside or outside the object. A weighted length term is used to keep the
      smoothness of curve and penalize the formulation of discontinuities. To prevent
      the level set function deviating from a signed distance function, a distance
      rectifying flow is also added to the model; therefore the time-consuming re
      initialization procedure is completely avoided. Experiments on both synthetic
      image and CT serial images demonstrate the feasibility and efficiency of the
      method.

PMID- 19384707
TI  - EEG dynamics of experienced Zen meditation practitioners probed by complexity
      index and spectral measure.
AB  - Changes in the electroencephalogram (EEG) characteristics in experienced Zen
      meditation practitioners (n = 23) during 40 minutes of meditation were compared
      with those in the matched controls (n = 23) taking a rest for 40 minutes.
      Averaged complexity index ([image omitted] ) evaluation and spectral analysis
      were measured in three intervals: the first, middle and the last 5-min segments
      of Zen meditation or relaxing rest. Significant increase in frontal alpha-1 (8-10
      Hz) and occipital beta power was found during meditation as compared with the EEG
      under the rest, whereas an average increase of theta power was observed in the
      controls. In meditation, brain dynamics exhibited high [image omitted] , which
      correlated with more beta activity. Control subjects showed no significant change
      in [image omitted] level. This distinction became more significant during the
      last 5 minutes of meditation over most electrodes. Deeper meditation state has
      been reported as having implications of increased beta power that can be more
      prominent by the approach of [image omitted] estimation. Our results substantiate
      the idea that long-term training with Zen-Buddhist meditation induces changes in
      the electro-cortical activity of the brain.

PMID- 19384708
TI  - Automatic adaptive onset detection using an electromyogram with individual
      difference for control of a meal assistance robot.
AB  - The onset detection of muscle activation is an essential issue in electromyogram
      (EMG) control. In this paper, a novel approach based on EMG power with automatic
      adaptive threshold is proposed to address this issue. The purpose is to develop
      an effective EMG-controlled meal assistance robot. Taking into account the
      individual difference such as contraction power and resting power, the threshold
      of onset detection is set with respect to the latest EMG signal. The results show
      the method is able to adjust automatically to avoid false alarms, and works well
      when the contraction power varies. Implementation of this EMG-controlled meal
      assistance robot may provide limb-deficient patients with an effective and
      comfortable human-machine assistance interface.

PMID- 19384709
TI  - Applicability of piezoelectric sensors for speech rehabilitation.
AB  - The applicability of piezoelectric sensors for speech rehabilitation was examined
      by setting vocalizing tasks for seven healthy young adults (four men and three
      women). A piezoelectric sensor was attached to the front of the neck and each
      seated subject was instructed to vocalize /a/ with subjective low and high tones
      and /pa/, /ta/, and /ka/ with a subjective middle tone. The three major findings
      were: (1) slow potential changes recorded at the start of these tasks were
      followed by rapid changes; (2) the tasks did not differ in the average range of
      the slow changes; (3) female subjects had higher average frequencies of rapid
      changes than male subjects. The frequencies and phases of the rapid changes
      paralleled the sound waves recorded in the neck during the tasks. Swallowing
      tasks verified the appropriateness of the recording system. The advantages of
      using piezoelectric sensors in the clinic are discussed.

PMID- 19384712
TI  - Feeding the fledgling repository: starting an institutional repository at an
      academic health sciences library.
AB  - In 2005, the Scott Memorial Library at Thomas Jefferson University started an
      institutional repository (IR), the Jefferson Digital Commons (JDC)
      <http://jdc.jefferson.edu/>. Originally intended as a showcase for faculty
      scholarship, it has evolved to serve also as a university press for original
      journals and newsletters, and as an institutional archive. Many lessons have been
      learned about marketing techniques, common IR issues, and advantages of an IR for
      a library. IR recruitment has come to be viewed as yet another form of collection
      development and has been integrated into all forms of the Library's outreach.
      Jefferson's academic health sciences environment has proven similar to other
      academic environments on issues of acceptance and participation.

PMID- 19384711
TI  - The effect of workload on biological monitoring of occupational exposure to
      toluene and n-Hexane: contribution of physiologically based toxicokinetic
      modeling.
AB  - A physiologically based toxicokinetic model was used to examine the impact of
      work load on the relationship between the airborne concentrations and exposure
      indicator levels of two industrial solvents, toluene and n-Hexane. The authors
      simulated occupational exposure (8 hr/day, 5 days/week) at different
      concentrations, notably 20 ppm and 50 ppm, which are the current threshold limit
      values recommended by ACGIH for toluene and n-hexane, respectively. Different
      levels of physical activity, namely, rest, 25 W, and 50 W (for 12 hr followed by
      12 hr at rest) were simulated to assess the impact of work load on the
      recommended biological exposure indices: toluene in blood prior to the last shift
      of the workweek, urinary o-cresol (a metabolite of toluene) at the end of the
      shift, and free (nonhydrolyzed) 2,5-hexanedione (a metabolite of n-hexane) at the
      end of the shift at the end of the workweek. In addition, urinary excretion of
      unchanged toluene was simulated. The predicted biological concentrations were
      compared with the results of both experimental studies among human volunteers and
      field studies among workers. The highest predicted increase with physical
      exercise was noted for toluene in blood (39 microg/L at 50 W vs. 14 microg/L at
      rest for 20 ppm, i.e., a 2.8-fold increase). The end-of-shift urinary
      concentrations of o-cresol and toluene were two times higher at 50 W than at rest
      (for 20 ppm, 0.65 vs. 0.33 mg/L for o-cresol and 43 vs. 21 microg/L for toluene).
      Urinary 2,5-hexanedione predicted for 50 ppm was 1.07 mg/L at 50 W and 0.92 mg/L
      at rest (+16%). The simulations that best describe the concentrations among
      workers exposed to toluene are those corresponding to 25 W or less. In
      conclusion, toxicokinetic modeling confirms the significant impact of work load
      on toluene exposure indicators, whereas only a very slight effect is noted on n
      hexane kinetics. These results highlight the necessity of taking work load into
      account in risk assessment relative to toluene exposure.

PMID- 19384713
TI  - Virtual Information for Patient Care-VIP care: an electronic collection to
      promote learning among third-year medical students.
AB  - Virtual Information for Patient Care (VIP Care) is an electronic collection of
      materials assembled to promote learning among Tufts University School of Medicine
      (TUSM) clinical clerks. Materials in the collection are selected on the basis of
      how well they match the core clerkship learning objectives. Consistent with TUSM
      curricular emphasis on utilizing evidence from research, VIP Care articles are
      culled, when possible, from Hirsh Health Sciences Library's electronic Evidence
      based Medicine (EBM) resource collection. This article describes the VIP Care
      collection within the context of the larger Patient Logs project of which it is a
      part and explains how this collection helps promote learning. It also reports on
      the process of compiling the collection as well as some of the methods librarians
      have adopted for publicizing the collection and keeping the content current.

PMID- 19384714
TI  - Virtual reference: chat with us!
AB  - Virtual chat services represent an exciting way to provide patrons of medical
      libraries with instant reference help in an academic environment. The purpose of
      this article is to examine the implementation, marketing process, use, and
      development of a virtual reference service initiated at the Massachusetts College
      of Pharmacy and Health Sciences and its three-campus libraries. In addition, this
      paper will discuss practical recommendations for the future improvement of the
      service.

PMID- 19384715
TI  - Evaluation of a new clinical librarian service.
AB  - In order to evaluate a new Clinical Medical Librarian (CML) service at Preston
      Medical Library in Knoxville, Tennessee, the three departments participating in
      the service were surveyed and interviewed. Participants in the study shed light
      on how much impact the attendance of a librarian at rounds and other meetings has
      had on their patient care decisions as well as their use of the library. Overall,
      the CML service has been well received by residents and faculty and will continue
      to serve at least these three departments.

PMID- 19384716
TI  - United States National Library of Medicine Drug Information Portal.
AB  - The Drug Information Portal is a free Web resource from the National Library of
      Medicine (NLM) that provides a user-friendly gateway to current information for
      more than 15,000 drugs. The site guides users to related resources of NLM, the
      National Institutes of Health (NIH), and other government agencies. Current drug
      related information regarding consumer health, clinical trials, AIDS, MeSH
      pharmacological actions, MEDLINE/PubMed biomedical literature, and physical
      properties and structure is easily retrieved by searching on a drug name. A
      varied selection of focused topics in medicine and drugs is also available from
      displayed subject headings. This column provides background information about the
      Drug Information Portal, as well as search basics.

PMID- 19384717
TI  - Supporting academic health centers with knowledge management: learning from the
      Web.
AB  - In a 2003 publication, the Association of Academic Health Sciences Libraries
      (AAHSL) made explicit the many ways in which a library might contribute to an
      academic health center's success through knowledge management (KM). Building on
      Success: Charting the Future of Knowledge Management within the Academic Health
      Center elucidated the ways in which a library can serve as the center of an
      organization's KM initiatives. The study and application of knowledge management
      tools is formidable; unlike information management (IM), the field of knowledge
      management has roots in a seemingly infinite and wide-ranging number of
      professional and academic disciplines. The planning of institutional KM
      initiatives is not commonly discussed, and history shows knowledge management
      projects often fail to thrive. This column introduces the topic of knowledge
      management and includes suggested Web-based resources for further understanding
      and project planning.

PMID- 19384718
TI  - Free-range RSS feeds and farm-raised journals: what to expect when using RSS as a
      TOC service.
AB  - Anyone who has tried to set up RSS feeds with or for a patron knows that the RSS
      feeds for e-journals can behave wildly, like free-range cattle, while the e
      journals that libraries subscribe to tend to be more like farm-raised cattle,
      because they are packaged for institutions rather than individuals. Because of
      this disconnect, the experience of teaching RSS feeds to one's patrons can be
      fraught with "oops" moments. Knowing what to expect can help librarians prepare
      to teach patrons to use RSS feeds without scaring them away from a powerful tool.
      This article will discuss some problems to expect and ways to work around them.

PMID- 19384719
TI  - Teaching first-year medical students where to go first: connecting information
      needs to e-resources.
AB  - The purpose of this project was to introduce first-year medical students to
      electronic resources that are best suited for different types of background
      questions. Specific questions from a case study were presented, and the students
      generalized them into a "type" of question. They then identified the best e
      resources for that type of question. This is their first introduction to the
      lifelong learning competency in the Indiana University School of Medicine
      competency-based curriculum.

PMID- 19384727
TI  - Microbial transformation of 18beta-glycyrrhetinic acid by Cunninghamella elegans
      and Fusarium lini, and lipoxygenase inhibitory activity of transformed products.
AB  - The microbial transformation of 18beta-glycyrrhetinic acid (1) by Cunninghamella
      elegans afforded a metabolite, 3beta,7beta-dihydroxy-11-oxo-olean-12-en-30-oic
      acid (2), while fermentation of 1 with Fusarium lini afforded a metabolite, 3,11
      dioxo-olean-12-en-30-oic acid (3). Compound 3 exhibited a potent lipoxygenase
      (LOX) inhibitory activity. The structures of these metabolites were elucidated on
      the basis of spectroscopic techniques.

PMID- 19384728
TI  - In vitro biological activity screening of Lycopodium complanatum L. ssp.
      chamaecyparissus (A. Br.) Doll.
AB  - This article reports the results of selected biological activities, including
      anticholinesterase, antioxidant, antibacterial, antifungal and antiviral
      properties, of the petroleum ether, chloroform and methanol extracts as well as
      the alkaloid fraction of Lycopodium complanatum L. ssp. chamaecyparissus (A. Br.)
      Doll (LCC, Lycopodiaceae) growing in Turkey. Anticholinesterase effect of the
      extracts was tested against both acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) at concentrations of 0.2 and 1 mg mL(-1) using
      microplate-reader assay based on Ellman method. Antioxidant activity of the LCC
      extracts was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging
      method at 0.2 mg mL(-1) using microplate-reader assay. Both DNA virus Herpes
      simplex (HSV) and RNA virus Parainfluenza (PI-3) were employed for antiviral
      assessment of LCC exracts using Madin-Darby Bovine Kidney and Vero cell lines.
      Antibacterial and antifungal activities of the extracts were screened against the
      bacteria: Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis,
      Acinobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Bacillus
      subtilis as well as the fungi: Candida albicans and C. parapsilosis. Only the
      petroleum ether extract of LCC possessed remarkable activity against both AChE
      and BChE at 1 mg mL(-1) (76.5 and 69.6%, respectively), whereas LCC extracts
      showed low free radical-scavenging activity. All of the extracts were found to be
      more effective against the ATCC strains than isolated ones, particularly S.
      aureus, while the extracts had moderate antifungal activity. On the other hand,
      we found that only the petroleum ether extract was active against HSV. In
      addition, we also analysed the content of the alkaloid fraction of the plant by
      capillary gas chromatography-mass spectrometry (GC-MS) and identified lycopodine
      as the major alkaloid (60.8%).

PMID- 19384729
TI  - Three di-O-caffeoylquinic acid derivatives from the heads of Cynara scolymus L.
AB  - Three di-O-caffeoylquinic acid derivatives were isolated from the ethanol
      extracts of the heads of Cynara scolymus L. Their structures were elucidated
      based on spectra analyses.

PMID- 19384726
TI  - 2008 Landis Award lecture. Inflammation and the autodigestion hypothesis.
AB  - Although long recognized in microvascular research, an increasing body of
      evidence suggests that inflammatory markers are present in human diseases. Since
      the inflammatory cascade serves as a repair mechanism, the presence of
      inflammatory markers in patient groups has raised an important question about the
      mechanisms that initiate the inflammatory cascade (i.e., the mechanisms that
      cause tissue injury). Using a severe form of inflammation, shock, and multiorgan
      failure, for which there is no accepted injury mechanism, we summarize studies
      that suggest that the powerful pancreatic digestive enzymes play a central role
      in the destruction of the intestine and other tissues if their
      compartmentalization in the lumen of the intestine and in the pancreas is
      compromised. Further, we summarize evidence that uncontrolled degrading enzyme
      activity in plasma causes proteolytic cleavage of the extracellular domain of
      membrane receptors and loss of associated cell functions. For example, in a model
      of metabolic disease with type II diabetes, proteolytic cleavage of the insulin
      receptor causes the inability of insulin to signal glucose transport across
      membranes. The evidence suggests that uncontrolled proteolytic and lipolytic
      enzyme activity may trigger the mechanism for tissue injury. The significance of
      such mechanisms remain to be explored in human diseases.

PMID- 19384730
TI  - Xanthones from roots of Calophyllum thwaitesii and their bioactivity.
AB  - Extracts from three Calophyllum species endemic to Sri Lanka were tested for
      antifungal and antioxidant activities. Of them, only the root methanol extract of
      Calophyllum thwaitesii showed activity, and the active extract on activity guided
      fractionation yielded four antifungal active and three inactive xanthones.
      Antifungal active xanthones were identified as 1,6-dihydroxy-5-methoxyxanthone, 1
      hydroxy-5,6-dimethoxyxanthone, 1-hydroxy-5-methoxyxanthone and 1-methoxy-5
      hydroxyxanthone, using spectroscopic methods and comparison with literature data.
      Inactive compounds were identified as 1-hydroxy-7-methoxyxanthone, 1,5-dihydroxy
      6-methoxyxanthone and 1,7-dihydroxy xanthone. This is the first report of above
      xanthones except the latter from C. thwaitesii. Further, five of the above
      xanthones along with thwaitesixanthone and calothwaitesixanthone, which have been
      previously reported from the root bark of the same species, showed free radical
      scavenging properties when tested with DPPH. Further, this is the first report of
      methylated xanthones from C. thwaitesii. Previous work on stem bark, root bark
      and the stem of the same species yielded only nonmethylated xanthones, indicating
      the absence of methylating enzymes in the plant. However, this new finding
      suggests the presence of methylating enzymes in the root stem of C. thwaitesii.

PMID- 19384731
TI  - The volatile constituents analysis of Lallemantia iberica (M.B.) Fischer & Meyer
      from Iran.
AB  - The volatile constituents of the aerial parts of Lallemantia iberica growing wild
      in Iran have been examined by GC-FID and GC-MS. Altogether, 11 compounds were
      identified, constituting approximately 97.2% of the oil. The oil of L. iberica
      consisted mainly of germacrene-D (33.7%), delta-3-carene (19.0%), iso
      caryophyllene (12.8%), sabinene (11.1%), alpha-terpinene acetate (6.5%) and
      limonene (4.4%).

PMID- 19384732
TI  - Characterisation of Blighia sapida (Sapindaceae) seed oil and defatted cake from
      Benin.
AB  - A sample of Blighia sapida seeds collected in Benin has been analysed and the
      results are compared to the scarcely available literature data. The chemical
      analysis of seed oil shows a saponification value of 145 and an iodine value of
      66, consistent with the high mono-unsaturated fatty acids (FAs) content (63.8
      wt%). The most interesting feature is the prominent concentration of eicosenoic
      acid (48.4 wt%). Arachidic acid being the main component within the saturated
      group, the C20 FAs fraction accounts for 68.4 wt%, thus making the peculiar
      composition of this oil. Among the unsaponifiable fraction (2.4 wt%), the major
      sterol is stigmasterol (54.6 wt%), surprisingly over passing beta-sitosterol.
      Tocols (338 ppm) contains mainly alpha- and gamma-tocopherol. Regarding the
      defatted cake, results show the prominent position of starch and a noticeable
      amount of proteins and fibers (44.2, 22.4, 15.6 wt%, respectively). Seventeen
      amino acids were identified together with valuable minerals (total ashes 3.5
      wt%). Possible uses of oil and defatted cake are discussed.

PMID- 19384733
TI  - An extract from Ricinus communis L. leaves possesses cytotoxic properties and
      induces apoptosis in SK-MEL-28 human melanoma cells.
AB  - Plants are an important source of several clinically useful anti-cancer agents. A
      volatile extract was obtained from Ricinus communis L. (Euphorbiaceae) leaves by
      standard hydrodistillation and subsequent extraction of the cohobated water in
      chloroform. GC-MS identified three monoterpenoids: 1,8-cineole, camphor and alpha
      pinene, and a sesquiterpenoid: beta-caryophyllene, as the main constituents. The
      leaf extract is cytotoxic to several human tumour cell lines in a dose-dependent
      fashion, with IC(50) values ranging between 10-40 microg mL(-1). Apoptosis was
      shown to be induced in SK-MEL-28 human melanoma cells at a concentration of 20
      microg mL(-1), as identified by means of morphological examination, nuclear
      staining and flow cytometric analysis of DNA content. Translocation of
      phosphatidyl serine to the cell membrane's external surface and loss of
      mitochondrial membrane potential were also detected. This study provides further
      insight into the potential use of mixtures of terpenoids as they occur in nature,
      as inducers of apoptosis in cancer cells.

PMID- 19384734
TI  - Chemical composition, antibacterial and antifungal activity of the essential oil
      of Thymbra spicata L. from Turkey.
AB  - The composition of the essential oil from aerial parts of Thymbra spicata L. from
      Turkey was analysed by GC-MS and its in vitro antimicrobial activity was
      examined. GC-MS analysis of the essential oil resulted in the identification of
      twenty-three constituents, representing 97.04% of the oil. The major compounds
      detected in the essential oil were carvacrol (60.39%), gamma-terpinene (12.95%),
      and p-cymene (9.61%). The in vitro efficacy of the essential oil against 21
      bacteria and seven Candida species was examined using disc diffusion and minimum
      inhibitory concentration (MIC) methods. The essential oil demonstrated strong
      anti-microbial activity in a wide spectrum against most microorganisms,
      particularly the yeasts tested. This is the first report on the anticandidal
      properties of the essential oil of T. spicata. In conclusion, this study confirms
      that T. spicata essential oil could be considered as a natural antimicrobial
      source.

PMID- 19384735
TI  - A new C-methylated homoisoflavanone and triterpenoid from the rhizomes of
      Polygonatum odoratum.
AB  - A new C-methylated homoisoflavanone together with four known rare methyl
      homoisoflavanones and one known 9,19-cyclolart triterpenoid were isolated and
      characterised from the rhizomes of Polygonatum odoratum. The structure of the new
      compound was determined as 3-(4'-methoxy-benzyl)-5,7-dihydroxy-6-methyl-8-methoxy
      chroman-4-one (1). The four known methyl-homoisoflavanones were determined as 3
      (4'-methoxy-benzyl)-5,7-dihydroxy-6,8-dimethyl-chroman-4-one (2), 3-(4'-hydroxy
      benzyl)-5,7-dihydroxy-6,8-dimethyl-chroman-4-one (3), 3-(4'-hydroxy-benzyl)-5,7
      dihydroxy-6-methyl-8-methoxy-chroman-4-one (4) and 3-(4'-hydroxy-benzyl)-5,7
      dihydroxy-6-methyl-chroman-4-one (5). The one 9,19-cyclolart triterpenoid was
      determined as 9,19-cyclolart-25-en-3beta,24 (R)-diol (6). Compound 2, 5, 6 were
      isolated for the first time from the Polygonatum genus. The compounds (1,3-6)
      were found to be strong against the growth of bacteria and plant pathogenic
      fungi.

PMID- 19384736
TI  - Pole walking for patients with breast cancer-related arm lymphedema.
AB  - Arm lymphedema is a well-known side effect of breast cancer treatment. Studies of
      the effect of physical exercise on arm lymphedema are very rare. The purpose of
      this study was to investigate the influence of pole walking on breast cancer
      related arm lymphedema when using a compression sleeve. Twenty-six women with
      unilateral arm lymphedema took part in a clinical study of pole walking on one
      occasion, 4 kilometers for 1 hour. Measurements were made before, immediately
      after, and 24 hours later. Results revealed no changes in total arm volume of the
      swollen arm, measured with water displacement method, or in subjective
      assessments of heaviness and tightness in the affected arm using visual analogue
      scale. Immediately after pole walking, a temporary increase in total arm volume
      of the healthy arm (P=0.037) was found. Twenty-four hours later, no differences
      were found compared to the measurements before walking. The median for perceived
      exertion immediately after pole walking, measured with Borg scale, was 11
      ("fairly light"). The results suggest that a controlled, short-duration pole
      walking program can be performed by patients with arm lymphedema, using a
      compression sleeve, without deterioration of the arm lymphedema.

PMID- 19384737
TI  - Effects of hippotherapy on people with cerebral palsy from the users'
      perspective: a qualitative study.
AB  - Although there is now some evidence for specific effects of hippotherapy on
      people with cerebral palsy, these studies fail to provide a comprehensive picture
      of the effects of hippotherapy. This was the first qualitative study to explore
      the hippotherapy experience of people with cerebral palsy from a user
      perspective. The effects of hippotherapy and their context were of particular
      interest. Seventeen users aged from 4 to 63, with or without their parents,
      participated in focus groups or individual interviews in six centres in Britain
      and in Germany. The main effects of hippotherapy, as identified by users and
      parents, are normalisation of muscle tone, improved trunk control, improved
      walking ability, carryover effects of hippotherapy to activities of daily living,
      and increased self-efficacy, confidence, and self-esteem. This study provided
      unique and new insights into the context in which hippotherapy happens, as well
      as its effects on impairment, activity, participation, and quality of life in
      people with cerebral palsy. The study's findings are integrated with the existing
      literature on motor learning and pedagogy to try to explain the complex effects
      of hippotherapy as reported by users and parents. A conceptual framework that
      illustrates these effects and their interactions is introduced.

PMID- 19384738
TI  - A grounded-theory investigation of patient education in physical therapy
      practice.
AB  - Patient education is a critical component of physical therapy and is used
      frequently in practice. Research describing the practice of patient education in
      physical therapy is scarce, however. Qualitative research methods can be used to
      describe the practice of patient education in physical therapy and to identify
      supportive theory. This study describes the practice of patient education
      grounded in data obtained from nine physical therapists in three settings:
      outpatient, acute care, and inpatient rehabilitation. From the data common themes
      are reported. From the themes, supportive theory can be identified. Results show
      four primary themes regarding patient education in physical therapy. First, the
      physical therapists in this study were not able to easily differentiate patient
      education from primary interventions. Second, the purpose of patient education
      was to empower patients toward self-management and prevention. Third, therapists
      used a patient-centered approach to decide upon content. Finally, each therapist
      used function or demonstration to assess the outcome of patient education
      interventions. The results of this study can be used to inform current
      practitioners, for future research and to identify theoretical underpinnings to
      support the practice of patient education in physical therapy.

PMID- 19384739
TI  - Effect of Maitland mobilization and exercises for the treatment of shoulder
      adhesive capsulitis: a single-case design.
AB  - The purpose of this single-case design (ABCBC) was to investigate the response of
      shoulder motions, pain, and function to two commonly used physiotherapy
      management approaches. An individual with stage three shoulder adhesive
      capsulitis was treated with exercise (phase B) and exercise plus mobilization
      (phase C). Initially, a "baseline" phase (phase A) when treatment had not started
      was established for comparison. Two types of Maitland "accessory" glenohumeral
      mobilization techniques, anteroposterior mobilization in shoulder flexion and
      longitudinal caudad in shoulder abduction, were evaluated during phase C. The
      Shoulder Pain and Disability Index (SPADI) was used to monitor pain and
      functional disability, and four shoulder movements (flexion, abduction, internal,
      and external rotations) were measured. The results were evaluated by using single
      case design analysis method of Split Middle Technique and visual observation. The
      SPADI scores deteriorated in phase A but improved in phase B1, C1, and B2. All
      four shoulder movements improved under both management approaches, although more
      gain in motion was observed when mobilizations were added to an exercise program.
      The exercise plus mobilization intervention shows promise as a cost-effective
      management. The deterioration in shoulder motion, pain, and function observed in
      phase A may suggest benefit of an earlier physiotherapy intervention.

PMID- 19384740
TI  - Intrasession reliability and influence of breathing during clinical assessment of
      lumbar spine postural control.
AB  - The aims of this study were to evaluate the influence of breathing when measuring
      lumbar postural control during a clinical progressive lumbar stabilization test
      (LST) and to estimate the intrasession reliability of the LST. The lumbar
      postural control index was calculated by using a biofeedback pressure unit. The
      LST was performed in two different positions (crook lying and upright) and two
      respiratory conditions (apnea and breathing) by 20 healthy individuals. The
      intrasession reliability of the lumbar postural control index of one trial was
      estimated with intraclass correlation coefficient (ICC) based on an Anova model.
      The results showed that the lumbar postural control index is similar between
      testing positions. There is an increase of the lumbar postural control index
      during breathing compared to the apnea. The reliability of the lumbar postural
      control index was fair to good (ICC 0.28-0.58). We also found that for the apnea,
      three trials had to be averaged to attain an ICC of 0.80 for both positions. The
      results of the present study indicate that the progressive LST can be similarly
      conducted in either supine or upright posture. Clinicians should be aware of the
      influence of breathing during LST. However, breathing could also serve as a
      clinical strategy to challenge lumbar spine postural control and stability during
      bracing therapeutic exercises.

PMID- 19384741
TI  - Atypical suboccipital vertebral artery blood flow in healthy subjects: case
      studies using real-time ultrasound.
AB  - Manual therapists and other professionals are using real-time ultrasound
      increasingly to visualize vessels and determine their diameter and blood flow.
      Four case studies are presented to show atypical ultrasound profiles of the
      suboccipital vertebral artery (VA3) in healthy, young individuals. VA3 diameters
      and blood flow velocities were measured with the subjects sitting, and the
      cervical spine in the neutral position then with active, full-range rotation to
      the left and right. None of the subjects reported any signs or symptoms of
      vertebrobasilar ischemia (VBI) during the measurement procedure, despite an
      absence of typical VA3 ultrasound profiles on one side in two of the individuals
      and a decreased unilateral VA3 blood flow in the other two subjects. Possible
      reasons for the atypical findings are proposed. Anatomical variations of VA3 and
      conditions such as obesity may give rise to atypical real-time ultrasound
      measurements of VA3 blood flow, particularly when associated with cervical spine
      rotation. The possibility of altered VA3 blood flow because of such factors,
      which may give rise to false-positive or false-negative findings in the standard
      VBI test, should be considered by manual therapists in pretreatment assessments
      and treatment programs in professional practice.

PMID- 19384743
TI  - Dyes from a twenty-first century perspective.
AB  - In June 2008, the Biological Stain Commission sponsored A Seminar on Dyes and
      Staining the purpose of which was twofold: first, to show that very useful
      information applicable to biomedical dyes and staining is available from
      unrelated disciplines and second, to summarize modern thinking on how dyes,
      solvents, and tissues interact to produce selective staining. In this
      introduction to the papers from the symposium, we acknowledge that biomedical dye
      research has declined as newer technologies have gained importance. We should
      point out, however, that dyes and staining still are vitally important. Moreover,
      needs abound for innovative studies concerned with dye analysis, synthesis, and
      mode of action. Concepts and tools from unrelated fields hold promise for
      significant breakthroughs in many areas of interest.

PMID- 19384744
TI  - Automating Giemsa banding of chromosomes: protocol for and evaluation of the use
      of a programmable, high-throughput automatic stainer.
AB  - The use of prometaphase chromosomes prepared for high-resolution imaging is
      essential for accurate cytogenetic investigations. The process of Giemsa
      chromosome banding (G-banding), however, is often time consuming and difficult to
      standardize owing to differing ambient conditions and inter-operator variability.
      Consequently, many laboratories currently are introducing automatic metaphase
      finder and analysis systems to achieve the goals of higher throughput of samples
      and more consistent chromosome quality. In this context, we investigated the use
      of automation to improve the G-banding process. We investigated the use of the
      Shandon Thermo Varistain Gemini automatic stainer to replicate the manual process
      of G-banding. We compared the current manual method and the automated procedure
      and found that automation provided equivalent quality, and increased consistency
      while decreasing the time required and reducing the cost per preparation.

PMID- 19384745
TI  - Cytological detection of Wolbachia in squashed and paraffin embedded insect
      tissues.
AB  - Wolbachia localization in situ is essential for accurate analysis of the
      infection and its consequences. Whole cell hybridization is proposed as an easy
      and rapid method for detecting Wolbachia cells in paraffin embedded tissues or
      testis squashes of Chorthippus parallelus (Orthoptera). Wolbachia is found in
      whole gonads and other adjacent tissues. A higher bacterial density, however, is
      observed in ovarioles and testis. Small independent bacteria with strictly
      cytoplasmic distribution are displayed. Bacterial density differences among
      individuals are also revealed.

PMID- 19384746
TI  - Staining of macromolecules: possible mechanisms and examples.
AB  - This review is based on a presentation given at the Biological Stain Commission
      meeting in June 2008. I discuss staining as an interaction between dye, solvent,
      and biological macromolecules. Most staining takes place in water, where the
      physico-chemical properties of the macromolecules are particularly important.
      Staining from aqueous solution is summarized. The first step is diffusion-ion
      exchange, which builds up the dye ion concentration close to the appropriately
      charged tissue constituents. While charge interactions are important for
      selectivity and build-up of dye ions around specific tissue and cell
      constituents, they have in most cases little to do with actual dye binding. The
      next step, actual binding, is predominantly between aromatic and other non-polar
      parts of the dye and corresponding groups in the tissue constituent. This results
      in a reduction of the total hydrophobic area exposed to water, hence the term
      hydrophobic interaction. Because dye binding is predominantly by dispersive
      forces, the larger the aromatic dye system and the fewer the number of charges on
      the dye, the greater the substantivity or affinity. Some relatively
      straightforward anionic or cationic one-step staining systems are discussed also.
      These include amyloid staining with Congo red, elastin staining with orceins,
      collagen staining with picrofuchsin, DNA-RNA staining with methyl green-pyronin
      Y, acid heteroglycan staining with Alcian blue, and metachromatic staining.

PMID- 19384747
TI  - Historic dyes and how to identify them.
AB  - The origin, production, and means of confirming the authenticity of some historic
      dyes are described. The underlying chemistry is revealed. The evolution of
      analytical techniques from early times, when the main criterion for a good
      textile dye was fitness for use, to more modern chromatographic techniques, where
      the emphasis is on chemical identity, is illustrated. Recent developments have
      led to smaller sample size requirements, greater speed of analysis and have led
      to a more detailed knowledge of the chemical components of historic dyes.

PMID- 19384748
TI  - Development of novel nitroxyl radicals for controlling reactivity with ascorbic
      acid.
AB  - Piperidine and pyrrolidine nitroxyl radicals (nitroxide) contain unpaired
      electrons and have been widely recognized as antioxidants, contrast agents, spin
      probes, radiation protective agents and polymerization mediators. Nitroxyl
      radicals can react with free radicals and reductants and their reactivities
      depend on the basic structure of the nitroxyl radicals themselves. However,
      reductants easily reduce these radicals and they lose their paramagnetic nature
      and function. Therefore, the aim of this study was to develop various functional
      nitroxyl radicals, particularly focusing on stability towards AsA through the
      improvement of the synthetic route for a series of 2,6-substituted nitroxyl
      radicals. Tetraethyl-substituted piperidine nitroxyl radical 8 exhibited
      resistance to AsA reduction and 2,6-dispiro-4',4''-dipyrane-piperidin-4-one-N
      oxyl 5 had a second-order rate constant 10-times greater than those of hydroxyl
      TEMPO and oxo-TEMPO. The 2,6-substituted compound offers various reactivities
      towards AsA and the possibility to be used as a new antioxidant, contrast agent
      and radical polymerizer.

PMID- 19384749
TI  - F(2)-isoprostanes, tocopherols and normal pregnancy.
AB  - This study investigates oxidative stress and antioxidants in normal human
      pregnancy and post-partum period. Thirty-seven healthy women with normal
      pregnancies were included. Both urinary and serum samples were collected
      throughout the pregnancy and post-partum period. Oxidative stress was estimated
      by measuring the reliable in vivo marker, namely 8-iso-prostaglandin F(2alpha) (8
      iso-PGF(2alpha,) an F(2)-isoprostane) and antioxidant status was evaluated by
      measuring alpha- and gamma-tocopherol in serum samples. Pregnancy was associated
      with successively increased levels of 8-iso-PGF(2alpha) with advancing
      gestational age. The median post-partum value corresponded to the values observed
      in early gestation and a significant decrease was observed from late pregnancy to
      the post-partum period. Lipid-adjusted alpha- and gamma-tocopherol levels
      decreased with advancing gestational age. This longitudinal study suggests that
      mild oxidative stress is involved in normal human pregnancy.

PMID- 19384750
TI  - Evaluation of antioxidant and anti-atherogenic properties of Glycyrrhiza glabra
      root using in vitro models.
AB  - The aim of present study was to evaluate antioxidant property of Glycyrrhiza
      glabra root extracts using in vitro models. The dose-dependent aqueous and
      ethanolic extracts demonstrated the scavenging activity against nitric oxide
      (concentration that caused 50% inhibition of nitric oxide radicals [IC(50)]=72
      and 62.1 microg/ml, respectively), superoxide (IC(50)=64.2 and 38.4 microg/ml,
      respectively), hydroxyl (IC(50)=81.9 and 63 microg/ml, respectively), DPPH
      (IC(50)=43.6 and 28.3 microg/ml, respectively) and ABTS(*+) (IC(50)=77.3 and 57.2
      microg/ml, respectively) radicals. Further, both extracts showed strong reducing
      power and iron-chelating capacities. In the Fe(2+)/ascorbate system, both
      extracts were found to inhibit mitochondrial fraction lipid peroxidation. In
      copper-catalyzed human serum and low-density lipoprotein oxidation models, both
      extracts significantly (P<0.05) lengthened the lag phase along with a decline in
      the oxidation rate, conjugated dienes, lipid hydroperoxides and thiobarbituric
      acid reactive substance formation. In conclusion, ethanolic extract of G. glabra
      possess considerable antioxidant activity and protective effect against the human
      lipoprotein oxidative system.

PMID- 19384751
TI  - Nutritional status of an economically-privileged convenience sample of urban
      children in Guatemala City.
AB  - BACKGROUND: The worldwide pandemic of overweight and obesity has now reached low
      income tropical societies. OBJECTIVE: To determine whether overweight or obesity
      is present among children from middle-class Guatemala City homes. METHODS: A
      total of 363 children, 173 boys and 190 girls aged 72-131 months, were included
      for height, weight, and abdominal circumference at its narrowest point (natural
      waist). RESULTS: Overall, 58.6% of subjects presented a body mass index within
      the normal Center for Disease Control and Prevention curve limits, whereas 3.9%
      fell below this range (low weight), 17.4% were in the risk of overweight range,
      and 20.1% were classified as overweight. The mean natural waist circumference was
      62.6+/-0.9 cm. The waist-circumference-to-height ratio had a median of 0.47, with
      36.9% of all children having a waist-circumference-to-height ratio exceeding the
      proposed 0.5 upper limit. CONCLUSIONS: Nutrition transition has reached the
      juvenile population of this Central American republic, at least in its urban,
      privileged groups.

PMID- 19384752
TI  - Paracoccidioidomycosis: an unusual presentation in a young girl disclosing an
      unnoted HIV-infection.
AB  - The association of paracoccidioidomycosis with AIDS is apparently less frequent
      than expected. The authors present an unusual case of paracoccidioidomycosis in a
      13-year-old female student which was later found to be the first opportunistic
      infection in the course of the patient's HIV-infection. The clinical presentation
      followed an accidental incised wound on the palmar region initially described as
      a 'sporotrichotic-chancre'. After good response under sulfamethoxazole
      trimethoprin, the patient relapsed and presented an associated oral candidiasis.
      HIV-infection was documented and additional investigation showed CD4(+) T
      cells=22/mm(3), CD8(+)=280 cell/mm(3) and viral load=4,043 log. This case report
      presents an uncommon dermatological-clinical picture in the youngest patient in
      which such association has been reported to date.

PMID- 19384753
TI  - Potential contribution of fungal infection and colonization to the development of
      allergy.
AB  - Fungi have long been recognized as an important source of allergens in patients
      with atopic disease. In this review, we explore the hypothesis that fungal
      exposures resulting in colonization or infection directly influence the tendency
      of an individual to develop allergic disease. According to this hypothesis,
      fungal exposures especially those early in life may influence the manner in which
      the immune response handles subsequent responses to antigen exposures. Studies
      detailing this potential connection between fungi have already provided important
      insights into the immunology of fungal-human interactions and offer the potential
      to provide new approaches and targets for the therapy of allergic disease. The
      first half of this review summarizes the data concerning fungal infections and
      asthma, including possible connections between fungal infections and urban
      asthma. The second half explores the potential role of the fungal
      gastrointestinal microbiota in promoting allergic inflammation.

PMID- 19384754
TI  - Insight into factors directing high production of eukaryotic membrane proteins;
      production of 13 human AQPs in Pichia pastoris.
AB  - Membrane proteins are key players in all living cells. To achieve a better
      understanding of membrane protein function, significant amounts of purified
      protein are required for functional and structural analyses. Overproduction of
      eukaryotic membrane proteins, in particular, is thus an essential yet non-trivial
      task. Hence, improved understanding of factors which direct a high production of
      eukaryotic membrane proteins is desirable. In this study we have compared the
      overproduction of all human aquaporins in the eukaryotic host Pichia pastoris. We
      report quantitated production levels of each homologue and the extent of their
      membrane localization. Our results show that the protein production levels vary
      substantially, even between highly homologous aquaporins. A correlation between
      the extents of membrane insertion with protein function also emerged, with a
      higher extent of membrane insertion for pure water transporters compared to
      aquaporin family members with other substrate specificity. Nevertheless, the
      nucleic acid sequence of the second codon appears to play an important role in
      overproduction. Constructs containing guanine at the first position of this codon
      (being part of the mammalian Kozak sequence) are generally produced at a higher
      level, which is confirmed for hAQP8. In addition, mimicking the yeast consensus
      sequence (ATGTCT) apparently has a negative influence on the production level, as
      shown for hAQP1. Moreover, by mutational analysis we show that the yield of hAQP4
      can be heavily improved by directing the protein folding pathway as well as
      stabilizing the aquaporin tetramer.

PMID- 19384755
TI  - Potential use of biodegradable nanoparticles for the photodynamic therapy of eye
      diseases.

PMID- 19384756
TI  - [Macular thickness might be a recurrence probability predictor in macular edema
      due to retinal vein occlusions treated with repeated intravitreal injections of
      antiangiogenics].

PMID- 19384757
TI  - [Pterygium surgery: comparative study of conjunctival autograft with suture
      versus fibrin adhesive].
AB  - PURPOSE: To compare recurrence rate, complications, and biomicroscopical findings
      after conjunctival autograft pterygium surgery with the use of a fibrin glue
      (Tissucol Duo, Baxter AG, Vienna, Austria) or suture (7-0 silk). METHODS:
      Patients with nasal pterygium were included in two groups of conjunctival
      autograft surgery. In 9 of them the graft was sutured to the surrounding
      conjunctiva and in 8 of them the graft was fixed to the conjunctiva using fibrin
      glue. RESULTS: 17 patients (17 eyes) 41.2% women and 58.8% men were surgically
      treated. Mean patient age was 59.8 years. Five of the patients presented
      recurrence for simple excision and 12 presented primary pterygium. The extent of
      corneal invasion was 2 to 4 mm. In the suture group, 33.3% of the patients
      experienced pain after surgery compared to none in the fibrin glue group. In the
      suture group, 44.4% of the patients presented inflammation after surgery compared
      to none in the glue group. One patient from the glue group lost the graft and
      presented a recurrence one month later. CONCLUSIONS: The use of fibrin glue in
      pterygium surgery reduces patient symptoms, inflammation and discomfort. The rate
      of recurrence seems to be similar in both procedures.

PMID- 19384758
TI  - [OCT in acute anterior uveitis].
AB  - PURPOSE: To evaluate macular thickening, the state of the optic disc and retinal
      nerve fibers layer (RFNL) in patients with an actual episode of acute anterior
      uvetis (AAU) by optical coherence tomography (OCT), and compare them with a
      control group. METHODS: In this prospective, cross-sectional, observational and
      controlled study we recruited 27 consecutive eyes of 20 patients with an actual
      episode of AAU, age and sex-matched with 40 healthy eyes of 20 volunteers. The
      age ranged between 8 and 78 years old, and all were evaluated by the <<fast
      macular thickness>>, <<fast optic disc>> and <<fast RFNL thickness>> scans by
      OCT. The patients were evaluated twice in a period of 1 month in order to obtain
      an average between the two measurements by OCT. RESULTS: We found a statistically
      significant increase in macular volume in AAU eyes compared with control eyes.
      Total macular volume in uveitic eyes was 7.3 SD 0.6 mm(3) and in healthy eyes was
      7.01 SD 0.3 mm(3) (mean SD standard deviation) (p<0.001). Indeed, we found a
      statistically significant increase in the superior RFNL thickness compared with
      controls. The Smax/Imax measurement was 1.05 SD 0.1 in pathological eyes and in
      healthy eyes it was 0.97 SD 0.1 (p<0.02). CONCLUSION: We found by OCT that
      patients suffering an AAU showed an increase in macular volume and superior RFNL
      thickness versus control eyes in the acute episode.

PMID- 19384759
TI  - [Retinopathy of prematurity in multiple births: risk analysis for plus disease].
AB  - PURPOSE: To analyze the risk factors associated with plus disease in retinopathy
      of prematurity (ROP). METHOD: Over a period of 8.5 years we carried out a
      prospective study of ROP in twins and triplets. Fifty-four multiple-birth infants
      with low birth weight (< or =1500 g) and low gestational age (32< or = weeks)
      were admitted to the University Hospital of Granada. RESULTS: Logistic regression
      analyses showed the following variables to be associated with an increased risk
      of plus disease: severe ROP, large area of avascular retina, low gestational age,
      low birth weight, a patent ductus arteriosus, length of mechanical ventilation,
      adverse events increase, low 5 min Apgar scores and poor postnatal weight gain
      (in the first 4 to 6 weeks of life). Using multiple logistic regression, only the
      grade of ROP (OR: 5.5; p < 0.009) and poor postnatal weight gain (OR: 0.58; p <
      0.04) were predictive factors of development of plus disease. Infants with
      <<plus>> disease gained an average 3.9 +/- 3.1 g/day in the first 6 weeks of
      life, compared to a mean of 11.84 +/- 8.3 g/day for those without plus disease (p
      < 0.0001). CONCLUSION: Advanced ROP stages and poor weight gain were the most
      significant factors associated with plus disease. Twins who gained weight at more
      than 7 g/day in the first 4-6 weeks of life had a significantly reduced risk of
      plus disease. A good weight gain is an effective strategy against avoidable
      blindness due to ROP.

PMID- 19384760
TI  - [Development of conjunctival hyperemia with the use of a fixed combination of
      latanoprost/timolol: systematic review and meta-analysis of clinical trials].
AB  - PURPOSE: To asses the association of conjunctival hyperemia with the use of a
      fixed combination of latanoprost/timolol, through a systematic review and meta
      analysis of clinical trials in patients with glaucoma. METHODS: A systematic
      review of published clinical trials of latanoprost/timolol and other competitors
      was conducted in Medline, Embasse and Cochrane Controlled Clinical Trials
      Register, between 2000 and 2007. Statistical analysis included calculation of the
      odds ratio (OR) with its 95% confidence interval (CI) using the fixed effects
      model of Mantel-Haenszel and the random effects model of Der Simonian and Laird.
      To assess the heterogeneity between trials the Cochrane Q test and the I(2) rate
      were calculated. The conjunctival hyperemia rates obtained were compared with the
      Chi-square test. RESULTS: A total of 8 clinical trials comparing
      latanoprost/timolol fixed combination with different therapeutic options were
      found. As trial heterogeneity was moderate (Q: 14.64; df=7; p=0.041; I(2)= 52.2%)
      a random effects model was used. The final OR was 0.47 (CI 95%: 0.24-0.90); p =
      0.024. The total conjunctival hyperemia incidence was 2.9% in the
      latanoprost/timolol group and 7.0% for the competitors (p<0.0001). CONCLUSIONS:
      The use of a fixed combination of latanoprost/timolol is associated with a
      significant reduction (53%; CI 95%: 10%-76%) in the development of conjunctival
      hyperemia against the other compared options for the treatment of glaucoma.

PMID- 19384761
TI  - [Intravitreal bevacizumab followed by focal laser for diffuse diabetic macular
      edema of recent progression. A clinical case].
AB  - CASE REPORT: We report the case of a 48-year-old man with diffuse diabetic
      macular edema of recent progression treated with two consecutive intravitreal
      injections of bevacizumab followed by focal laser therapy, with good anatomic and
      functional response. DISCUSSION: Diffuse diabetic macular edema is difficult to
      manage and frequently requires multiple therapies. We propose the use of
      bevacizumab as a strategy to reduce diffuse macular edema, facilitating the
      application of laser therapy.

PMID- 19384762
TI  - [Post-traumatic striate melanokeratosis in a Caucasian woman].
AB  - CLINICAL CASE: A fair-skinned woman presented marked striate melanokeratosis in
      her left eye related to recurrent corneal erosion. The source of pigmentation was
      a conjunctival melanosis. The conjunctival melanosis responded to treatment with
      topical mitomycin, while the corneal pigmentation persisted. DISCUSSION: Striate
      melanokeratosis is a condition described in dark-skinned patients who show a well
      defined pigmentation of the limbal area, with only one case of striate
      melanokeratosis reported previously in a Caucasian person. The stimuli for this
      proliferation are corneal lesions or melanosis close to the limbus. Avoiding both
      stimuli are the main steps in its management.

PMID- 19384764
TI  - [The eyes in the Code of Hammurabi].

PMID- 19384763
TI  - [Isolated conjunctival involvement in Langerhans cell histiocytosis].
AB  - CASE REPORT: A 43-year-old woman referred for a hyperemic node in the inferior
      conjunctival fornix. No improvement was observed after 10 days of antibiotic and
      anti-inflammatory topical treatment, so biopsy-extirpation was performed.
      Histopathological and immunohistochemical findings suggested the diagnosis of
      Langerhans cell histiocytosis (LCH). No findings of extraocular manifestations
      were shown after an intensive clinical and analytical investigation. DISCUSSION:
      LCH is a disease with different organ manifestations whose diagnosis depends on
      histological findings. We present a patient with isolated conjunctival
      affectation, which to our knowledge is the third case published in the
      literature.

PMID- 19384765
TI  - [Niels Stensen. Copenhagen, 1638 - Schwerin, 1686].

PMID- 19384766
TI  - [Central vision disorders--visual phenomena caused by lesions of the primary
      visual cortex and associated regions].

PMID- 19384767
TI  - [Communications of the 101st Annual Meeting of the Swiss Society of Ophthalmology
      SOG/SSO, Interlaken, September 10 - 13, 2008].

PMID- 19384768
TI  - [Primary or Secondary Prophylaxis of AMD with Anthocyanins?].
AB  - Bilberry extracts containing anthocyanins have become rather popular within the
      last 2 years among patients with age-related macular degeneration (AMD) in
      Switzerland as a medication for primary or secondary prophylaxis. So far human
      study results concerning safety and efficacy in AMD patients are not available.
      The present state of the scientific literature concerning the use of anthocyanins
      with relation to AMD will be analysed in this review.

PMID- 19384769
TI  - [Present state of the development and clinical use of dyes and staining
      substances for vitreoretinal surgery].
AB  - Staining of intraocular tissue has become an established tool of vitreoretinal
      procedures within the last 8 years. This review describes the presently available
      dyes and markers and their use during vitreoretinal procedures.

PMID- 19384770
TI  - Vitreoretinal interface changes in acute-onset postoperative endophthalmitis.
AB  - BACKGROUND: The aim of this study was to assess the significance of different
      clinical appearances of the vitreoretinal interface in the surgical management of
      acute postoperative endophthalmitis. PATIENTS AND METHODS: 22 patients underwent
      vitrectomy and were divided intraoperatively in 3 groups according to the degree
      of vitreoretinal interface changes: 10 patients had white infiltrates in the
      vitreous cortex but no retinal hemorrhages (group A), eight patients had white
      infiltrates in the vitreous cortex and retinal hemorrhages (group B) and four
      patients had advanced vitreous opacification, strong vitreoretinal adhesions and
      retinal hemorrhages (group C). In group A vitrectomy was performed and the
      vitreous cortex was removed cautiously, while in groups B and C the vitreous
      cortex was not removed in the first procedure. RESULTS: Visual acuity improved in
      14 patients, remained stable in 2 patients and deteriorated in 6 patients. The
      visual prognosis was better in group A. None of the cases was complicated with
      retinal detachment following vitrectomy, but in groups B and C 37.5 % and 50 % of
      the patients, respectively, went into phthisis. CONCLUSIONS: Intraoperative
      assessment of the vitreoretinal interface insult in acute postoperative
      endophthalmitis contributes to an optimal surgical management, and it also has a
      prognostic value.

PMID- 19384771
TI  - The impact of infectious ocular emergencies on hospital resources.
AB  - BACKGROUND: Infectious ocular emergencies cannot be pre-planned, need a more
      labour-intensive treatment and are often associated with prolonged
      hospitalisation. The aim of this study is to assess the impact of infectious
      ocular emergencies on hospital resources and identify changing trends over the
      last 10 years. PATIENTS AND METHODS: In a retrospective chart review 13,587
      inpatient records from 1998 to 2007 were analyzed for the reason for emergency
      hospitalization, treatment data, length of hospitalizations and economical
      impact. RESULTS: 341 cases of severe infectious ocular emergencies with the need
      for emergency hospitalization were identified. The annual incidence of such
      emergencies increased continuously and has more than doubled during the last 10
      years (51 vs. 24 annual cases). Within the same period the average
      hospitalization time of all non-infectious patients decreased from 5.41 to 4.95
      days while inpatient stay due to infectious ocular emergencies decreased from
      10.13 to 8.18 days. The average nursing effort was 4.26 hours per day in the
      infectious group, while electively admitted patients had an average requirement
      for nursing time of only 2.92 hours per day. CONCLUSION: The increase in
      infectious-related hospitalizations, their unpredictability and the need for a
      more intensive treatment regime have an increasing impact on hospital resources.

PMID- 19384772
TI  - Predictability of microkeratome-dependent flap thickness for DSAEK.
AB  - BACKGROUND: The recommended thickness of the graft lamella in Descemet's
      stripping automated endothelial keratoplasty (DSAEK) is 120 - 180 microm. To
      adjust for the large variation in central corneal thickness (CCT) of eye bank
      donor corneas, microkeratome plates of different heights are available. The aim
      of this study was to evaluate the lamella thickness predictability of different
      keratome plates in a clinical routine setting. METHODS: In a prospective study of
      60 consecutive DSAEK procedures, CCT was measured with a 50 MHz ultrasound
      pachymeter after meticulous epithelium removal immediately before and after
      lamella creation. Selected plate thickness was 300, 350, or 400 micro,
      respectively. Cutting depth was calculated by subtracting the remaining CCT of
      the deep lamella after the cut from the initial CCT before the cut. RESULTS: The
      mean (+/- SD) cutting depth was 320 +/- 45 microm with the Amadeus 350 keratome,
      317 +/- 48 microm with the Moria 300 keratome, 388 +/- 58 microm with the Moria
      350 keratome and 467 +/- 94 microm with the Moria 400 keratome. Neither the
      duration nor the type of donor preservation had an effect on the accuracy of the
      cutting depth. CONCLUSION: The mean cutting depth for the DSAEK keratomes is more
      accurate than the cutting depth of the same keratome heads designed for LASIK.
      This might be due to the fact that DSAEK lamellas were cut after complete
      epithelial removal. Despite the accurate mean cutting accuracy, there is a
      substantial variation between individual cuts which have to be taken into
      consideration.

PMID- 19384773
TI  - [Safety of treatment with tacrolimus ointment for anterior segment inflammatory
      diseases].
AB  - BACKGROUND: The off-label use of topical tacrolimus (Protopic) for inflammatory
      external eye diseases is gaining popularity. However, there are no reports on the
      safety profile of this new treatment option. PATIENTS AND METHODS: We treated six
      patients with different inflammatory eye diseases with topical tacrolimus
      (Protopic 0.03 %) as off-label use in addition to the conventional anti
      inflammatory treatment. Patients were interviewed for side effects and serum drug
      concentrations were measured under steady state conditions one hour after topical
      application of tacrolimus ointment. RESULTS: Two patients reported a slight
      burning sensation immediately after application, in one patient we found a slight
      worsening of the dry eye problems. No patient abandoned the treatment due to side
      effects. Serum drug concentrations remained below the analytical threshold in all
      cases (< 1.5 ng/ml). CONCLUSIONS: Tacrolimus for the topical treatment of
      anterior segment inflammatory eye diseases is well tolerated without detectable
      systemic drug resorption.

PMID- 19384774
TI  - In vivo confocal microscopy of keratic precipitates in fuchs heterochromic
      uveitis syndrome.
AB  - BACKGROUND: In vivo confocal microscopy (IVCM) enables large-field in vivo
      examination of the corneal endothelium and corneal precipitates. Keratic
      precipitates (KP) are prominent features of Fuchs Heterochromic uveitis syndrome
      (FHUS). The aim of this study was to investigate the effect of KP on the corneal
      endothelium. PATIENTS AND METHODS: Eight patients with clinically diagnosed FHUS
      and KP between July 2007 and May 2008 underwent slit lamp examination and IVCM.
      KP (shape, area), endothelial cell count and percentage of hexagonal cells were
      measured and compared with an age-matched control group and with not affected
      healthy contralateral eyes. RESULTS: The age of participants ranged between 26
      and 67 years. KP had a diameter ranging between 37 to 217 microm (mean 137
      microm) with an average area of KP of 5630 microm (2). The mean endothelial cell
      count in the study group was 2541 +/- 299 cells/mm (2), 2722 +/- 312 cells/mm (2)
      in the control group (p = 0,18) and 2397 +/- 192 cells/mm (2) in not affected
      contralateral eyes (p = 0.17). The percentage of hexagonal cells was 59.1 % in
      FHUS study group and 69.1 % in the control group (p = 0.0002) and 68.6 % in not
      affected contralateral eyes (p = 0.0495). CONCLUSIONS: KP in FHUS cause a focal
      damage of endothelial cells reflected in a decreased percentage of healthy
      hexagonal cells. The degree of endothelial cell damage seems to be low as it does
      not lead to a significant reduction in the endothelial cell count.

PMID- 19384775
TI  - Comparison of dynamic contour tonometry with Goldmann applanation tonometry
      following Descemet's stripping automated endothelial keratoplasty (DSAEK).
AB  - BACKGROUND: Intraocular pressure (IOP) measurements using Goldmann applanation
      tonometry (GAT) are influenced by central corneal thickness (CCT) whereas dynamic
      contour tonometry (DCT) allows for IOP measurements independent of CCT. After
      Descemet's stripping automated endothelial keratoplasty (DSAEK) the CCT is,
      compared to healthy eyes, increased. The objective of this prospective study was
      to compare IOP measurements obtained by DCT and GAT in patients after a DSAEK
      procedure. PATIENTS AND METHODS: DCT and GAT were performed 3 and/or 6 months
      after DSAEK. Comparison of means was performed using the Wilcoxon signed-ranks
      test. RESULTS: In total, 50 IOP measurements on 33 eyes were obtained. Mean CCT
      was 621 (+/- 60) microm. Overall correlation between GAT and DCT was good,
      however, in some patients a remarkable difference between pressure readings of up
      to 10.8 mmHg was observed. Mean IOP readings obtained by DCT were significantly
      higher (20.9 +/- 5.9 mmHg) than those obtained by GAT (19.1 +/- 6.5 mmHg; p =
      0.0002). However, the difference between GAT and DCT readings was not influenced
      by the thickness of the transplanted lamella. DISCUSSION: The well-known
      difference in mean pressure readings between DCT and GAT was not affected by the
      increase in CCT following DSAEK. IOP readings with the GAT seem not to be
      influenced by the increase in CCT. Because of the remarkable differences in
      individual pairs of IOP measurements, both GAT and DCT should be used after
      DSAEK.

PMID- 19384776
TI  - Channelography: imaging of the aqueous outflow pathway with flexible
      microcatheter and fluorescein in canaloplasty.
AB  - BACKGROUND: The aim of this study is to present a new approach to visualize the
      aqueous outflow system during glaucoma surgery using a flexible microcatheter and
      fluorescein, called channelography. PATIENTS AND METHODS: Schlemm's canal was
      unroofed in a standard non-penetrating dissection technique in patients
      undergoing canaloplasty. A flexible microcatheter (iTrack 250A) was introduced
      into the canal and advanced 360 degrees . Fluorescein sodium tracer was injected
      through the microcatheter during cannulation and the aqueous outflow pathway was
      video-recorded and evaluated. RESULTS: In the early phases, episcleral veins
      which were thinner, branched and fairly straight originating from the limbus
      could clearly be distinguished from ciliary veins which were thicker, tortuous
      vessels leaving posterior to the limbus. The filling quality of the episcleral
      veins varied among glaucoma patients. The permeability of the trabecular
      meshwork/inner wall of Schlemm's canal determined by fluorescein diffusion into
      the anterior chamber differed in this regard as well. In the late phases, the
      sclera stained with fluorescein, and no details were detectable. CONCLUSIONS:
      This qualitative in-vivo method was simple, safe, and enabled us to visualize the
      details of the aqueous outflow system during canaloplasty. Filling
      characteristics of episcleral venous network as well as trans-trabecular
      diffusion may reflect the clinical status of the outflow pathway in glaucoma
      patients, and may be helpful in the prediction of the surgical outcome in
      canaloplasty.

PMID- 19384777
TI  - Volumetric blood flow measurement in the ophthalmic artery using colour Doppler.
AB  - BACKGROUND: Herewith we present a new method for measurement of the volumetric
      blood flow in absolute units in the ophthalmic artery. PATIENTS AND METHODS: A
      Philips EnVisor HD ultrasound unit with a 12 - 3 MHz linear transducer was used
      to measure flow in the ophthalmic artery in 8 healthy young subjects. The
      transducer was mounted on a custom-made holder which enabled precise and
      reproducible positioning in 3 axes as well as in rotation angle. Blood flow
      velocity and vessel diameter were measured during 10 consecutive heartbeats. The
      measurements were ECG-gated. Blood vessel diameter and blood flow velocity were
      calculated in an average heartbeat cycle. Hence blood volume over time within a
      heartbeat cycle as well as blood flow in mL/min were determined. Simultaneously,
      cardiovascular parameters have been recorded by Finapres. Short time
      reproducibility (5 measurements on day 1) and long time reproducibility (5 days
      once daily) as well as interindividual coefficient of variation were evaluated.
      RESULTS: Average blood flow in the ophthalmic artery in all measurements was 39.7
      mL/min. The short-term intraindividual coefficient of variation was 24.1 +/- 9.2
      %, the long-term coefficient 32.0 +/- 13.8 %. Interindividual coefficient of
      variation was 32.8 %. CONCLUSIONS: Our method allows volumetric blood flow
      measurements in the ophthalmic artery in absolute units, reproducible to a
      limited extent.

PMID- 19384778
TI  - Hydrogel intraocular lens exchange: five-year experience.
AB  - BACKGROUND: This study presents an evaluation of the preoperative and
      postoperative best corrected visual acuity (BCVA), as well as of the incidence of
      perioperative and postoperative complications after opacified hydrogel
      intraocular lens (IOL) exchange. PATIENTS AND METHODS: We exchanged opacified
      hydrogel IOLs (Hydroview H 60 M, Bausch & Lomb) in 55 patients (55 eyes).
      Preoperative and postoperative BCVA were compared. Intraoperative and
      postoperative complications were recorded. Follow-up period ranged from 3 months
      to 24 months. RESULTS: Mean BCVA improved significantly from 0.05 preoperatively
      to 0.4 at 3 months postoperatively and to 0.2 at the end of the follow-up period.
      Forty patients (72.7 %) reported visual improvement. The procedure was uneventful
      in 30 eyes (54.5 %) with complete removal of the opacified IOL optics and
      haptics. Intraoperative complications included partial zonular dehiscence in 10
      eyes (18.2 %), en block capsular bag-IOL extraction in 2 eyes (3.6 %), posterior
      capsule rupture in 2 eyes (3.6 %), hyphema in 3 eyes (5.5 %), retained haptics in
      8 eyes (14.5 %). Postoperative complications included corneal decompensation in 5
      eyes (9.1 %), cystoid macular edema in 15 eyes (27.3 %), elevated intraocular
      pressure in 6 eyes (10.9 %), and retinal detachment in 1 eye (1.8 %).
      CONCLUSIONS: Visual acuity improved after opacified hydrogel IOL exchange,
      however, coexistent ocular morbidity as well as the appearance of serious
      postoperative complications may not yield the expected results. For these reasons
      extensive informed consent is mandatory.

PMID- 19384779
TI  - Capsular opacification after vitreous-sparing cataract surgery in children.
AB  - BACKGROUND: The aim of this study was to evaluate different methods of
      intraocular lens (IOL) implantation and posterior capsule management in the
      absence of vitrectomy with respect to visual axis opacification (VAO) in
      children. PATIENTS AND METHODS: Seventy-three eyes of African children undergoing
      cataract extraction and IOL implantation between 1998 and 2001 were evaluated. In
      all eyes, the IOL haptics were placed in the bag and the vitreous was preserved.
      The IOL optic and posterior capsule were managed in the following 3 ways: The IOL
      optic was captured behind the posterior capsule in conjunction with posterior
      capsulotomy (PC) in 47 eyes (group 1). The IOL optic was implanted in the bag
      with PC in 14 eyes (group 2) and without PC in 12 eyes (group 3). Cox
      proportional hazard analysis and Kaplan-Meier survival curves were performed to
      evaluate the incidence of Elschnig pearls (EP) and VAO. RESULTS: Elschnig pearls
      developed in 14.9 % of the patients in group 1, in 56.8 % in group 2 and in 91.7
      % in group 3. The occurrence of EP depended significantly on optic capture (p <
      0.001) and child's age (p < 0.05), but not on PC (p = 0.084) and eye side (p =
      0.1). The persistence of visual axis clarity depended significantly on optic
      capture (p < 0.001) but not on PC. CONCLUSIONS: In vitreous-sparing cataract
      surgery, posterior capsule opening does not effectively prevent VAO unless it is
      in conjunction with IOL optic capture.

PMID- 19384780
TI  - Late postoperative opacification of hydrogel intraocular lenses: analysis of 13
      explanted lenses.
AB  - PURPOSE: We report the clinical, morphological, and ultrastructural findings of
      13 consecutively explanted opacified Hydroview(R) (hydrogel) intraocular lenses
      (IOLs). Our purpose was to provide a comprehensive account on the possible
      factors involved in late postoperative opacification of these IOLs. PATIENTS AND
      METHODS: Thirteen consecutive opacified hydrogel IOLs (Hydroview H 60 M, Bausch &
      Lomb) were explanted due to the significant visual impairment they caused. The
      IOLs underwent macroscopical examination, transmission electron microscopy (TEM),
      scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS),
      and electrophoresis for protein detection. Three unused control Hydroview IOLs
      served for comparison. RESULTS: Macroscopical examination showed a diffuse or
      localized grey-whitish opacification within the IOL optic. TEM confirmed the
      presence of lesions inside the optic in all the explanted IOLs and revealed 3
      patterns of deep deposits: a) diffuse, thick, granular, electron-dense ones; b)
      small, thin, lattice-like ones, with prominent electron-lucent areas; and c)
      elongated electron-dense formations surrounded by electron-lucent halos. SEM
      showed surface deposits on four IOLs. EDS revealed oxygen and carbon in all IOLs
      and documented calcium, phosphorus, silicon and/or iron in the deposits. Two of
      the patients with iron in their IOLs had eye surgery prior to their
      phacoemulsification. Iron correlated well with the second TEM pattern of deep
      lesions, whereas calcium with the third TEM pattern. No protein bands were
      detected on electrophoresis. Control lenses did not show any ultrastructural or
      chemical abnormality. CONCLUSIONS: The present study supports the presence of
      chemical alterations inside the polymer of the optic in late postoperative
      opacification of Hydroview IOLs. This opacification does not follow a unique
      pathway but may present under different ultrastructular patterns depending on the
      responsible factors. Mechanical stress during surgery may initiate a sequence of
      events where ions such as calcium, phosphorus, silicon, and/or iron, participate
      in a biochemical cascade that leads to gradual alteration of the polymer network.
      Intraocular inflammation due to previous operation may be a factor inducing
      opacification through increase of iron-binding capacity in the aqueous humour.
      Calcification accounts only partially for the opacification noted in this type of
      IOL.

PMID- 19384781
TI  - Retinal vessels in patients with multiple sclerosis: baseline diameter and
      response to flicker light stimulation.
AB  - BACKGROUND: Transparency of ocular media enables the precise quantitative
      analysis of vessels of retina, a neuronal tissue which can be affected by
      multiple sclerosis (MS). PATIENTS AND METHODS: Eyes with no history of optic
      neuritis (non-ON eyes) of 21 patients with MS were examined with Retinal Vessel
      Analyzer. Segments of vessels of 500 microm length were measured proximal and
      distal from the optic disc and compared to those of 21 age- and gender-matched
      controls. Baseline diameters and peak response to flicker light stimulation of
      retinal vessels were analyzed. RESULTS: MS eyes had thinner arterioles (p = 0.02)
      and thicker venules (p = 0.008) than controls: arterioles 111 +/- 14 microm
      (proximal), 99 +/- 11 microm (distal) in MS eyes and 121 +/- 15 and 107 +/- 9 in
      controls, respectively. Values for venules were 157 +/- 18 and 136 +/- 20 (MS);
      147 +/- 15 and 119 +/- 20 (controls). Peak response was higher in MS eyes than in
      controls for arterioles (p = 0.007), but comparable for venules (p = 0.35).
      CONCLUSION: Narrower arterioles and wider venules might be a consequence of
      subclinical swelling of optic nerve axons in eyes with negative history of ON in
      MS patients.

PMID- 19384782
TI  - Rigidity of retinal vessels in patients with multiple sclerosis.
AB  - PURPOSE: The aim of this study was to analyze pulse wave propagation in the
      ocular circulation by assessing the phase delay between retinal arterioles and
      venules and calculating the pulse delay between the retinal and choroidal
      circulations in MS patients and in control subjects. SUBJECTS AND METHODS: Twenty
      patients with multiple sclerosis (38.3 +/- 6.2 years) and twenty healthy subjects
      (37.4 +/- 15.2 years) were examined with the Retinal Vessel Analyzer. In
      addition, an average peripapillary RNFL (retinal nerve fiber layer) thickness was
      measured by means of ocular coherence tomography in MS patients. The phase delay
      between the arteriole and venule pulsations was assessed at three sites: in the
      close retinal vicinity of the disc, 1 - 2 disc diameters and 3 - 4 disc diameters
      away from the disc. Assuming that venules are counterphased to the choroidal
      circulation, a choroid-to-retina pulse delay was calculated. RESULTS: The choroid
      to-retina pulse delay was 0.26 +/- 0.11, 0.27 +/- 0.13 and 0.34 +/- 0.15 sec in
      eyes with history of optic neuritis (ON-eyes); in eyes of MS patients without
      such a history (non-ON eyes) the corresponding values were 0.27 +/- 0.14, 0.29 +/
      0.11 and 0.30 +/- 0.15 sec, and in control eyes 0.32 +/- 0.19, 0.38 +/- 0.16 and
      0.45 +/- 0.20 sec, respectively, at three sites centrifugal from the disc. The
      choroid-to-retina pulse delay was significantly longer in healthy control eyes
      than both in ON eyes (p = 0.012) and non-ON eyes of MS patients (p = 0.004). The
      interocular difference of the choroid-to-retina pulse delay and OCT RNFL
      thickness showed a significant correlation in MS patients (Pearson r = 0.54, p =
      0.015; Spearman R = 0.66, p = 0.0016). CONCLUSION: Patients with multiple
      sclerosis seem to demonstrate an increased rigidity of the retinal vessels. The
      interocular difference in retinal vessel rigidity was significantly correlated
      with the interocular difference in RNFL thickness in MS patients.

PMID- 19384783
TI  - The disc damage likelihood scale (DDLS): interobserver agreement of a new grading
      system to assess glaucomatous optic disc damage.
AB  - BACKGROUND: The disc damage likelihood scale (DDLS) is a new grading system to
      estimate the amount of optic disc damage in glaucoma patients. The objective of
      this study was to assess the interobserver agreement of the DDLS and the cup/disc
      ratio. PATIENTS AND METHODS: The reproducibility of the DDLS and the cup/disc
      ratio was measured by two masked observers (one glaucoma specialist and one of
      two resident physicians in their first 6 months of training) staging 42 eyes of
      25 patients with glaucoma or ocular hypertension. Disc size, cup/disc ratio and
      DDLS were documented and the Cohen's kappa was calculated as a measure for
      interobserver agreement. RESULTS: The interobserver agreement for the cup/disc
      ratio was good (Cohen's kappa 0.803). For the DDLS, the interobserver agreement
      was even better (Cohen's kappa 0.902). DISCUSSION: Unlike the cup/disc ratio,
      which focuses on the excavation, the DDLS is based directly on the thickness of
      the neuroretinal rim and takes into account the optic disc size. Therefore, the
      DDLS estimates the glaucomatous damage of the optic disc more precisely than the
      currently used method. Although this new grading system is more complicated to
      use in clinical practice, the interobserver agreement for the DDLS in our study
      setting was very good.

PMID- 19384784
TI  - Retinal angiomatous proliferations: when should we suspect them and how should we
      detect them?
AB  - BACKGROUND: The aim of this study was to identify the clinical and angiographic
      features of retinal angiomatous proliferations (RAPs) in patients with age
      related macular degeneration. PATIENTS AND METHODS: 26 eyes of 24 patients with
      RAPs were retrospectively reviewed. All patients had colour and red-free
      photographs, and fluorescein (FA) and indocyanine-green angiography (ICGA). The
      biomicroscopic and angiographic characteristics were evaluated and video
      angiograms were analysed for staging the RAPs. RESULTS: The total number of RAPs
      was 29. Stage 1 was present in 3/29, stage 2 in 3/29 and stage 3 in 23/29 with a
      chorio-retinal anastomosis identified in 21 of these 23 eyes. The total number of
      retinal vessels involved were 83, 35 were arteries and 48 were veins. RAPs were
      seen in ICGA as hot spots in all but one case where it appeared as a plaque. A
      retinal pigment epithelial detachment (PED) was observed in 22/26 eyes. Cystoid
      macular oedema was observed in 13/26 eyes in FA and intraretinal ICG leakage in
      6/26 eyes. Hard exudates were present in 21/26 eyes. Retinal haemorrhages were
      present in 23/26 eyes; all but one were intraretinal and had a size of less than
      half of the optic disc diameter. The RAP was bilateral in 2/24 patients.
      CONCLUSIONS: Clinicians should suspect the diagnosis of RAP when hard exudates,
      small intraretinal haemorrhages, PED or a hot spot in ICGA are present. Both
      fluorescein and ICG video-angiography provide adequate temporal resolution and
      vascular flow examination leading to easier RAP staging and identification of the
      anastomosis.

PMID- 19384785
TI  - Macula-off retinal detachment--a matter of time?
AB  - BACKGROUND: The aim of this study was to determine the influence of the lag time
      between macular detachment and surgical intervention on post-operative visual
      acuity gain in patients with rhegmatogenous macula-off retinal detachment.
      PATIENTS AND METHODS: We retrospectively evaluated the medical records of 62
      consecutive patients having undergone scleral buckling surgery for rhegmatogenous
      macula-off retinal detachment. The correlation of gender, age, refraction, number
      of retinal breaks, development of cataract during follow-up, pre-operative visual
      acuity and timing of surgical intervention with final visual acuity and post
      operative visual acuity gain were determined. Mean follow-up time was 12.7
      months. RESULTS: A correlation with final visual acuity was found for pre
      operative visual acuity and lag between the beginning of symptoms and surgical
      intervention. A correlation with visual acuity gain was found only for timing of
      surgical procedure. When divided into subgroups operated after 0, 1-3, 4-6, or 7
      9 days, respectively, visual recovery was better the earlier the patients
      underwent surgical repair. Compared to surgery at day 0, statistical significance
      was found only for patients operated 4 or more days after the occurrence of
      symptoms. CONCLUSION: The first three days seem to represent a relatively safe
      period during which surgery for macula-off retinal detachment may be postponed
      without compromising the patient's visual prognosis.

PMID- 19384786
TI  - The treatment of choroidal neovascularizations in age-related macular
      degeneration using either Avastin or Lucentis.
AB  - BACKGROUND: Either Avastin or Lucentis was used in our clinic to treat choroidal
      neovascularizations in age-related macular degeneration. The number of injections
      necessary for drying the macular findings was especially assessed. PATIENTS AND
      METHODS: From April 2006 to August 2008 324 eyes were treated with Avastin, and
      from January 2007 to August 2008 348 eyes were treated with Lucentis. The
      intravitreal injections with Avastin (1.25 mg in 0.05 mL) were performed every
      six weeks, and with Lucentis (0.05 mg in 0.05 mL) every four weeks until the
      macular findings were considered to be dry. Fluorescein angiography and optical
      coherence tomography were used for the diagnosis and for the checks which were
      carried out every twelve weeks. The visual acuity was measured with an ETDRS
      chart. RESULTS: The treatment with Avastin is completed in 319 eyes with an
      average improvement of the visual acuity of 5.1 letters after 3.3 injections, and
      with Lucentis in 226 eyes with an average improvement of the visual acuity of 6.4
      letters after 3.4 injections (p = 0.24; one way ANOVA). CONCLUSION: Both of the
      drugs allow the drying of the macular findings in the great majority of the cases
      after a short time and lead to a quite similar improvement of the visual acuity.
      A definitive stabilization of the disease after stopping the treatment is not
      foreseeable.

PMID- 19384787
TI  - [Eales' disease--10 years experience with a rare disease].
AB  - BACKGROUND: Eales' disease is an uncommon vasoproliferative retinal disease
      affecting otherwise healthy young men. We report on our treatment results in a
      large patients group with long-term follow-up. PATIENTS AND METHODS: The
      treatment results in 50 eyes (35 patients) with Eales' disease, that were
      consecutively treated from May 1995 to August 2005, were analysed
      retrospectively. Recorded data included age, sex, race, association of systemic
      disease, medications, laboratory evaluation and the surgical treatment. Mean
      follow-up was 5.8 years (minimum: 3.2, maximum: 8.6 years). RESULTS: Systemic and
      laboratory evaluations detected a factor V Leiden mutation (4x),
      vestibuloauditory problems (1x) and migraine (1x). 10 eyes with peripheral non
      perfusion, teleangiectasia and mild neovascularisations were treated by scatter
      laser photocoagulation alone. 18 eyes with advanced neovascularisations/vitreous
      haemorrhages received cryocoagulation too. 14 eyes with persistent or recurrent
      bleedings despite coagulation therapy and/or development of tractional retinal
      detachment were treated by vitrectomy. 5 of them received a silicone oil
      endotamponade. All eyes could be stabilised without further bleedings. Visual
      acuity increased in 25 eyes. Only 5 eyes showed a visual loss. The visual results
      (rate of improvements and the stages of visual acuity as well) were the best in
      those eyes that received vitrectomy. CONCLUSIONS: These results suggest that
      early retinal laser and cryocoagulation and - if necessary - vitrectomy in due
      time may led to a stabilised retina without further bleedings and visual
      improvement too. Coagulopathy could play a role in the pathogenesis of Eales'
      disease.

PMID- 19384788
TI  - [Response of retinal vessel diameter to flicker-light in vasospastics compared to
      healthy controls].
AB  - BACKGROUND: Vascular dysregulation is considered to be a risk factor in several
      ophthalmic diseases. The purpose of this study was to evaluate the reaction of
      retinal vessels to flicker light in otherwise healthy subjects with a vasospastic
      propensity. PATIENTS AND METHODS: Thirty healthy Caucasians, aged between 18-35
      years were recruited for this study and grouped into vasospastics, based on a
      history of frequent cold hands, even in summer, with concordant findings in
      nailfold capillary microscopy, or as controls, if such a history was absent. The
      reaction of the retinal vascular diameter to flicker light was observed in a
      distance of two to three discs diameters away from the optic nerve head with the
      retinal vessel analyser. Three phases of flicker light of twenty seconds followed
      by baseline light phases of eighty seconds were recorded. The maximal
      vasodilatory amplitude of each flicker phase was determined and the results
      averaged. RESULTS: The maximal average dilatory amplitude at the arterial side
      reached (mean +/- SD) 2.9 +/- 1.7 % and 4.8 +/- 2.6 % of the baseline amplitude
      respectively in vasospastic subjects and in healthy controls (t = 2.34; p =
      0.025). The reaction at the venous side was statistically comparable in both
      groups. CONCLUSIONS: Otherwise healthy, vasospastic subject disclosed an altered
      reaction of the retinal vasculature to flicker light in this study.

PMID- 19384789
TI  - [Arteriovenous crossing sheathotomy in branch retinal vein occlusion].
AB  - BACKGROUND: The aim of this study is to report on arteriovenous sheathotomy in
      branch retinal vein occlusion (BRVO) with a long-term follow-up and examine the
      visual field effects of this surgical approach. PATIENTS AND METHODS: In a
      clinical trial 36 eyes with branch retinal vein occlusion (22 eyes with
      ischaemia, 14 eyes with chronic macular oedema) underwent surgical decompression
      accompanied by peeling of the membrana limitans interna after prior isovolemic
      haemodilution for 3 months had been unsuccessful. RESULTS: All eyes showed a
      significant reduction of macular oedema 3 months after surgery. During follow-up
      (median: 26.4 months) visual acuity increased in 24/36 eyes and was stabilised in
      8/36 eyes. We observed haemorrhages at the dissection site (5x), vitreous
      haemorrhages (12x) and retinal holes at the vitreous base (2x). Goldmann
      perimetry revealed paracentral scotomas in 3 eyes, which had been treated by
      arteriovenous dissection relatively close to the optic disc. In 16/22 eyes with
      ischaemic thromboses the visual field was narrowed in the affected quadrant.
      CONCLUSIONS: The results of arteriovenous sheathotomy in BRVO are encouraging
      because we observed increase of visual acuity in 67% of the eyes in spite of an
      unsuccessful haemodilution during 3 months before. However, whether its benefits
      outweigh potential surgical complications as visual field defects remains to be
      determined.

PMID- 19384790
TI  - [Long-term follow-up after surgery for exodeviation].
AB  - BACKGROUND: In strabismus surgery the challenge is the preoperative determination
      of the surgical dosage. We assessed the long-term follow-up after strabismus
      surgery for exodeviations and evaluated the employed dosage. PATIENTS AND
      METHODS: We present a study of 53 consecutive patients who underwent surgery for
      exodeviations. One year postoperative results were analysed based on strict
      criteria. Out of the original group of 53 patients we could evaluate the long
      term follow-up in 18 patients, after an average period of 13 years. The criteria
      for patients with intermittent exotropia and decompensating exophoria after one
      year and in the long-term follow-up were determined as follows: very good:
      orthophoria or orthotropia with exo- or esophoria less than 5 PD; good:
      orthotropia with exo- or esotropia less than 10 PD; satisfactory: orthotropia
      with exo- or esophoria > 10 PD but less than the preoperative angle; bad:
      constant eso- or exotropia or > preoperative angle. For patients with a constant
      divergent strabismus the following criteria were determined: very good:
      orthophoria or orthotropia with exo- or esophoria less than 5 PD; good: exo- or
      esophoria less than 10 PD or tropia of 5 degrees (microstrabismus); satisfactory:
      exo- or esophoria > 10 PD or exo- or esotropia > 10 PD but < preoperative angle;
      bad: same as preoperative or more. A subgroup analysis of 41 patients who
      underwent monolateral combined rectus muscle surgery was performed regarding
      their long-term follow-up (average: 13 years) as well. Concurrently the patients
      completed a questionnaire. RESULTS: One year postoperatively 6 outcomes were very
      good, 14 good, 31 satisfactory and 2 were poor. On average 13 years
      postoperatively the same patients were evaluated based on the same strict
      criteria. No outcome was very good, 4 good, 12 satisfactory and 2 were poor. The
      judgement of the patients in the questionnaire was at both times clearly better.
      The exo-shift in the first postoperative year was 3.5 degrees , in the next on
      average 12 years the mean divergent strabismus angle increased by another 2.9
      degrees. CONCLUSIONS: The outcome evaluation after a long-term follow-up showed
      amazingly stable results compared to the follow-up after one year. With a more
      aggressive dosage we could have achieved more orthophoric results, but also more
      undesirable overcorrections.

PMID- 19384791
TI  - [Rectus muscle transposition for the treatment of complex ocular motility
      disorders].
AB  - BACKGROUND: Transposition techniques alter the muscle paths thereby creating new
      directions of muscle force. Extraocular muscle transposition procedures have been
      used to treat abducens palsy, Duane's retraction syndrome, double-elevator palsy
      and other complex ocular motility abnormalities. The purpose of this study was to
      evaluate the surgical and functional results of rectus muscle transposition in
      patients with different aetiologies of severe ocular motility deficits. PATIENTS
      AND METHODS: Between 1992 and 2008 rectus muscle transposition surgery has been
      performed on 31 patients. In this retrospective case series one patient with an
      abducens nerve palsy is presented as an example. In addition, six patients with
      motility disorders of different aetiologies who had transposition manoeuvers were
      evaluated. Preoperative, surgical and postoperative data are reported. RESULTS:
      Rectus muscle transposition has been performed because of severe functional loss
      of the lateral rectus muscle, the superior rectus muscle or the medial rectus
      muscle as well as in myopic strabismus fixus. One of the patients had traumatic
      sixth nerve palsy. The underlying pathology in patients who had superior
      transposition of the horizontal rectus muscles were double-elevator palsy,
      congenital oculomotor nerve palsy and hypotropia caused by sphenoid wing
      hypoplasia. A nasal transposition of the vertical rectus muscles was performed in
      traumatic and tumour-associated muscle loss of the medial rectus muscle. The
      large preoperative deviations were markedly reduced postoperatively and even
      ocular motility partially improved. CONCLUSIONS: Transposition surgery seems to
      be a suitable procedure for the treatment of complex ocular motility disorders.
      In cases of a complete lack of function of an extraocular muscle or in complex,
      uncommon conditions, which are difficult to treat with any other surgery, muscle
      transposition seems to be an effective procedure.

PMID- 19384792
TI  - Relation of body mass index and blood pressure to subjective and objective acral
      temperature.
AB  - BACKGROUND: Vascular dysregulation, indicated by a positive history of cold
      extremities, has been postulated as a risk factor for a number of ocular
      diseases. In order to further characterize the phenotype of vasospastic persons,
      we tested the association between cold extremities, body mass index (BMI) and
      blood pressure (BP) in a cohort of healthy subjects. PATIENTS AND METHODS:
      Questionnaire data were collected from one hundred and seventeen healthy
      subjects. Based on the history of cold hands and feet they were divided in three
      groups, reporting "never", "sometimes" and "always" having cold extremities. BP
      was measured sphygmomanometrically and as an objective measure of finger
      temperature, it was recorded at the fingertips with an infrared thermometer
      (IRT). Two-way analysis of variance with gender as one, and group selection as
      the second factor was performed separately for BMI and mean BP. The correlation
      of finger temperature with BMI and BP was analyzed by the Pearson regression.
      RESULTS: Gender distribution was male/female = 41/16, 13/21 and 4/22, for the
      three groups, respectively, and average age 45.8 +/- 13.0 years. For BMI, factor
      groups was highly significant (p = 0.0012) with both genders behaving comparably
      (interaction p = 0.18). For BP the corresponding p values were: factor group p =
      0.026, interaction p = 0.89. Correlation coefficients between IRT and BMI were
      0.34 (p = 0.0002) and between IRT and BP 0.24 (p = 0.009). CONCLUSION: A
      statistical significant association is present in healthy subjects between body
      mass index and blood pressure on one, and cold extremities on the other side,
      defined subjectively as well as measured objectively. This relationship is gender
      independent.

PMID- 19384793
TI  - Adrenaline-induced chronic ocular hypertension in adult rabbits.
AB  - BACKGROUND: The aim of this study was to develop a new animal model to enhance
      our understanding of the biological pathomechanisms involved in glaucoma.
      MATERIALS AND METHODS: Forty white giant rabbits were divided into a treated (N =
      30) and a control group (N = 10). Boli of adrenaline hydrochloride (0.1 mL 0.1%
      solution) were repeatedly injected into the veins of the ears of the rabbits and
      physiological saline in the control group, respectively, for three months.
      Intraocular pressure (IOP) and outflow facility of the aqueous humour were
      measured prior to, during and after treatment (4-6 months, 7-9 months, 10-12
      months). RESULTS: In comparison to the control group, the adrenaline-treated
      group showed a significant increase in IOP both during treatment (25%) and 12
      months after treatment (57%). Comparative analysis further showed that the
      aqueous humour outflow facility of the treated group increased by 16.5% during
      the treatment, and showed a continuous decrease of 60 % after treatment.
      CONCLUSION: This rabbit model could be useful for further investigations of the
      pathomechanisms involved in glaucoma.

PMID- 19384794
TI  - [Contribution to comparative ophthalmo-morphology: the eye of the brown trout].
AB  - BACKGROUND: The aim of this study was to assess similarities and differences
      between the trout eye and the human eye. MATERIALS AND METHODS: Gross and
      microscopic examinations of the formalin-fixed eyes of each five trout and human
      eyes (donor eyes not suitable for keratoplastic) were carried out. RESULTS:
      Compared to the human eye, the trout showed a flattening of the anterior
      posterior axis, and cartilage-stabilized sclera. The peripheral cornea was much
      thicker than the central, had a multilayered thick epithelium, a distinct Bowman
      layer, and an implied Descement membrane. A ring-shaped ligament filled up the
      angle of the anterior chamber and linked the iris to the cornea. The lens showed
      a spherical aspect with a thick capsule and missing zonular fibres, however, a
      suspensory ligament of a superior part of the lens was present. Ventrally, at the
      end of the falciform process, a small, pigmented structure was in contact with
      the lens. The retina was similarly differentiated, but the choroid showed special
      structures like choroidal gland, falciform process and the argentea compared to
      the human eye. CONCLUSIONS: Great variations between the ocular anatomy of the
      trout and the human exist. However, the retina of the trout is fully
      differentiated and remarkably similar to that of human eyes.

PMID- 19384795
TI  - Large upper eyelid full-thickness defects reconstructed only with an anterior
      lamella.
AB  - BACKGROUND: The purpose of this study is to report a surgical procedure that only
      uses anterior lamella structures (muscle and skin) to reconstruct large upper
      eyelid full-thickness total defects. PATIENTS AND METHODS: The study design is a
      non-comparative retrospective interventional small case series. Three patients
      with upper eyelid full-thickness (anterior and posterior lamellae) total-defect
      (horizontal extent: > 3/4 length, vertical extent: > 15 mm) after tumor excision
      (basal cell, squamous cell, or Merkel's cell carcinoma). As intervention an
      eyelid reconstruction using only a rotation/advancement muscular-skin flap was
      used. The outcome was postoperatively an upper eyelid anatomic cosmetic
      appearance and lid-closure function. RESULTS: Good anatomic cosmetic-appearance
      and lid-closure function were achieved soon after surgery. No remarkable ocular
      as well as extra-ocular side effects or complications were noted. CONCLUSIONS: In
      a single-stage procedure it appears possible to repair upper eyelid full
      thickness total defects by reconstructing only the anterior lamella. With this
      procedure there is no need to reconstruct the posterior lamella and/or to use
      tissue from other eyelids or parts of the body.

PMID- 19384796
TI  - [Ophthalmological findings in microcephaly-lymphoedema-chorioretinal dysplasia
      syndrome].
AB  - BACKGROUND: Microcephaly-lymphoedema-chorioretinal dysplasia (MLCRD) is a rare
      syndrome characterized by microcephaly, chorioretinal dysplasia, lymphoedema and
      a characteristic facial phenotype. The exact mode of inheritance is uncertain,
      autosomal dominant, recessive and X-chromosomal cases have been reported. HISTORY
      AND SIGNS: A three-month-old boy with intrauterine growth retardation and
      microcephaly was referred to our clinic. The ophthalmic examination revealed a
      left eye with a persistent hyperplastic primary vitreous. On funduscopy of the
      right eye pale optic disc, chorioretinal dysplasia with pigmentary and atrophic
      changes and falciform folds were noted. General morphological changes and
      ophthalmological findings led to the diagnosis of MLCRD-syndrome. THERAPY AND
      OUTCOME: Eye examinations of the parents and the grandparents did not show any
      retinal changes, therefore an autosomal dominant inheritance was excluded.
      CONCLUSIONS: An ophthalmological examination in children with microcephaly and
      facial dysmorphies is essential. Parents and grandparents should also be
      considered for eye examination if a child has chorioretinal dysplasia and
      microcephaly.

PMID- 19384797
TI  - [Positive polymerase chain reaction for Bartonella henselae in conjunctival
      granuloma].

PMID- 19384798
TI  - Pseudomonas cepacia (PC) contamination of a cornea conservated in organ culture.

PMID- 19384799
TI  - [Atypic uveitis as an indicator of neurosyphilis].

PMID- 19384800
TI  - Bilateral serous retinal detachment in a case of preeclampsia.

PMID- 19384801
TI  - Rhegmatogenous retinal detachment in toxoplasmic chorioretinitis.

PMID- 19384802
TI  - Delayed occurrence of subretinal silicone oil after retinal detachment surgery in
      an optic disc pit--a case report.

PMID- 19384803
TI  - Spontaneous closure of a traumatic macular hole.

PMID- 19384804
TI  - Spontaneous closure of a traumatic macular hole.

PMID- 19384805
TI  - Spontaneous closure of macular hole: one-year follow-up with spectral-domain
      optical coherence tomography.

PMID- 19384806
TI  - Acute massive suprachoroidal hemorrhage after photodynamic therapy in a patient
      treated with warfarin.

PMID- 19384807
TI  - Pigment epithelium detachment following carotid cavernous sinus fistula.

PMID- 19384808
TI  - Optic disc dysplasia in cerebral gray matter heterotopias: a valuable clinical
      clue.

PMID- 19384809
TI  - [An unusual cause of orbital inflammation].

PMID- 19384810
TI  - [Readiness for organ donation: analysis of a survey for health themes].
AB  - BACKGROUND: Currently, organ transplantation is the treatment of choice for
      patients with chronic or acute organ failure. However, due to a lack of donor
      organs, every day three patients die on the waiting list for transplantation. At
      the same time there is a high potential of organ donors that is not utilized.
      Statements concerning the number of potential donors are possible only to a
      limited extent at present. Objective of this study was to collect the rate of
      holders of organ donor cards among the employees of the city of Essen before a
      targeted awareness raising campaign had been carried out. PATIENTS AND METHODS: A
      questionnaire was sent out to the employees of the city of Essen in 2007. Gender,
      age and the "indicator for readiness for organ donation" were stratified and
      analyzed according to the holding of organ donor cards. The indicator reflects
      the evaluation of health awareness in the respondents. RESULTS: Altogether, 1 814
      questionnaires were evaluated. 20 % of the respondents were holding an organ
      donor card at the time of the survey. No association between gender (p-value
      0.17) respectively age (p-value 0.79) and the possession of an organ donor card
      could be detected. 23 % of the respondents who regularly worked out or donated
      blood were identified as organ donor card holders. This is significantly more (p
      value < 0.0001) than in respondents where this criterion did not apply.
      CONCLUSION: In order to optimize the potential of organ donors in the long term,
      it is necessary to reconsider and advance attitude towards the readiness for
      organ donation. Further spreading of information and education as well as
      transparency in the transplantation medicine are essential for this project.

PMID- 19384811
TI  - [Peripheral polyneuropathy and bilateral optic neuropathy during treatment of
      chronic hepatitis C].
AB  - HISTORY AND CLINICAL FINDINGS: A 54-year-old female patient with recently
      confirmed chronic hepatitis C, genotype Ib and positive HCV-RNA was admitted for
      interferon induction therapy. EXAMINATIONS: Physical examination findings were
      normal. Ultrasound examination of the abdomen revealed slightly compacted liver
      structure with otherwise no pathological findings. Laboratory results showed
      marginally increased GPT value at 46 U/l with HCV-RNA of 769,000 U/ml. All other
      laboratory results were within the reference range. There was no indication for
      autoantibodies. THERAPY AND COURSE: After one-week induction therapy with
      interferon-alpha (IFN-alpha2a) plus ribavirin and amantadine, maintenance therapy
      with pegylated interferon-alpha (PEG-IFN-alpha2a) plus ribavirin and amantadine
      was initiated. Complete virus elimination was achieved after two and a half
      months. Five months after onset of therapy, painful peripheral neuropathy of the
      limbs occured and after one more month, severe vision impairment with opticus
      neuropathy and bilateral papilledema developed. Simultaneously, peripheral
      polyneuropathy progressed with additional motoric deficits. Interferon therapy
      was terminated and the patient received high-dose corticosteroids which resulted
      in an improvement of neuropathic complaints. Eight months later, only discrete
      bilateral vision impairment with optic nerve atrophy remained. CONCLUSION: Side
      effects occurring with interferon-alpha therapy and pegylated interferon-alpha
      therapy are generally low and well tolerated. However, in individual cases - as
      in our patient - side effects including severe peripheral neuropathy and optic
      neuropathy have been observed. In these cases, interferon therapy must be
      terminated immediately as severe damage of nerves may result.

PMID- 19384812
TI  - [84-year-old woman with diffuse abdominal pain and blood impurities in the
      stool].

PMID- 19384813
TI  - ["Liquid ecstasy": gamma-butyrolactone withdrawal delirium with rhabdomyolysis
      and dialysis dependent renal failure].
AB  - HISTORY AND ADMISSION FINDINGS: A 24-year-old man with known abuse of gamma
      butyrolactone (GBL) was found with stupor and myoclonies on all extremities. He
      had been known to have ingested 2 ml of pure GBL every half an hour. Decubiti
      were detected on the knuckle of the right foot, on both elbows and at the rump.
      INVESTIGATIONS: Laboratory findings revealed signs of severe rhabdomyolysis and
      renal failure as well as elevated markers of inflammation. Other routine
      laboratory parameters were normal. A toxicological screening revealed no signs of
      an acute intoxication. DIAGNOSIS, TREATMENT AND COURSE: A GBL withdrawal syndrome
      was diagnosed. The treatment of agitation and myoclonies required repeated
      applications of benzodiazepines. Because of the resulting respiratory depression
      the patient had to be intubated. To cope with myoclonies and other symptoms of
      substance withdrawal we had to administer midazolame and clonidine continuously
      until day four. Because of acute renal failure resulting from rhabdomyolysis
      hemodialysis was necessary three times. After 19 days the patient was transferred
      to a psychiatric clinic. CONCLUSIONS: Primary care physicians treating patients
      with a coma of unknown cause always have to think of the possibility of GBL
      withdrawal. The treatment will be symptomatic.

PMID- 19384814
TI  - [Strategies of mechanical ventilation in chronic obstructive pulmonary disease
      (COPD)].

PMID- 19384815
TI  - [Unlicensed use of drugs: measures to minimize risks].
AB  - INTRODUCTION: The use of unlicensed drugs is an unsettling issue in medical
      circles. "Dear Doctor Letters", batch recalls and important notifications about
      them are not provided systematically. Unlicensed use is, however, sometimes the
      only promising option for further medical treatment. Approaches to improve
      vigilance of pharmaceutical agents are available in many countries. An outline of
      legislation on and experiences with unlicensed use in selected industrial
      countries is reviewed in this article. Research data, documentation and
      assessment of the legal status of unlicensed drugs in selected industrial
      countries were obtained and compared to the situation in Germany. Expert
      interviews with specifically recruited representative samples from academic
      centers as well as regulatory and industrial sources, health technology
      assessments and health insurance data were analysed (N = 44, t = 20-120 min,
      transcribed verbatim). Approaches and limitations of licensing in different
      countries compared: Granting of a license has been an obligatory condition and
      there has been a duty of disclosure (sometimes with the right of prohibition) as
      well as reservations on the granting of permission. Central administration of
      data has made it possible to quantify and identify required drugs and ensure
      surveillance of their use. High administrative costs involved in giving notice of
      approval has caused delays in patient care. Procedures by which a medical doctor
      has to obtain permission affect physicians' freedom of action. Unlicensed and off
      label use is variably regulated across the analysed settings. Legislation and
      regulation continue to be highly heterogeneous. Most promising approaches include
      the duty of disclosure, which allows quantification of use and surveillance of
      safety, including the right of recall while ensuring doctors' freedom to treat
      with medicinal products.

PMID- 19384816
TI  - [Challenge in diabetes therapy: effects of glitazones beyond blood glucose
      control].
AB  - Not just since the results of ACCORD, ADVANCE and VADT were published, it is
      clear that lowering blood glucose alone does not reduce the cardiovascular risk
      of patients with type 2 diabetes. In fact, many studies also indicate that some
      treatment strategies may even have adverse effects. To treat type 2 diabetes
      appropriately, the co-morbidities such as diabetic dyslipidaemia, hypertension or
      nephropathy must also be taken into account. Thiazolidinediones reduce insulin
      resistance thus allowing to direct the treatment of type 2 diabetes towards its
      pathophysiologic origin. Due to their mechanism of action, thiazolidinediones not
      only lower blood glucose but have also beneficial effects on inflammatory and
      atherogenic parameters, blood pressure and microalbuminuria. Furthermore
      pioglitazone improves dyslipidaemia and reduces mortality, myocardial infarction
      and stroke in high risk patients. Effects of rosiglitazone on the cardiovascular
      risk are yet unclear. Numerous studies document the efficacy and safety of
      thiazolidinediones and provide a basis for an evidence-based therapeutic approach
      beyond blood glucose control.

PMID- 19384817
TI  - Inhibition of the mevalonate pathway rescues the dexamethasone-induced
      suppression of the mineralization in osteoblasts via enhancing bone morphogenetic
      protein-2 signal.
AB  - We used dexamethasone (DEX)-treated osteoblastic MC3T3-E1 cells, and investigated
      the effects of an AMP-activated protein kinase activator, 5-aminoimidazole-4
      carboxamide-1-beta- D-ribonucleoside (AICAR), a Rho-associated protein kinase
      inhibitor, fasudil hydrochrolide, as well as HMG-CoA reductase inhibitors,
      simvastatin and pitavastatin, all of which inhibit the mevalonate pathway. DEX
      (10(-8) M) significantly enhanced mRNA expression of bone morphogenetic protein
      (BMP)-2 antagonists, follistatin and Dan, and addition of each of 10 (-4) M
      AICAR, 10 (-5) M fasudil, 10(-6) M simvastatin, and 10(-6) M pitavastatin
      significantly reversed the enhancement in mRNA expression of follistatin and Dan
      and stimulated that of BMP-2 in the cells (p<0.05). DEX (10(-8) M) also
      significantly suppressed mineralization in the cells, and addition of each of
      these agents significantly reversed the suppression of mineralization (p<0.05).
      These findings suggest that the mevalonate pathway was involved in glucocorticoid
      induced osteoblast dysfunction, and that its inhibition might promote bone
      formation through BMP-2 and alleviate glucocorticoid-induced osteoporosis.

PMID- 19384818
TI  - Heat shock protein 27 modification is increased in the human diabetic failing
      heart.
AB  - Chronic conditions like diabetes mellitus (DM) leading to altered metabolism
      might cause cardiac dysfunction. Hyperglycemia plays an important role in the
      pathogenesis of diabetic complications including accumulation of methylglyoxal
      (MG), a highly reactive alpha-dicarbonyl metabolite of glucose degradation
      pathways and increased generation of advanced glycation endproducts (AGEs). The
      aim of this investigation was to study the extent of the MG-modification
      argpyrimidine in human diabetic heart and in rat cardiomyoblasts grown under
      hyperglycemic conditions. Left ventricular myocardial samples from explanted
      hearts of patients with cardiomyopathy with (n=8) or without DM (n=8) as well as
      nonfailing donor organs (n=6), and rat cardiac myoblasts H9c2 treated with
      glucose were screened for the MG-modification argpyrimidine. The small heat shock
      protein 27 (Hsp27) revealed to be the major argpyrimidine containing protein in
      cardiac tissue. Additionally, the modification of arginine leading to
      argpyrimidine and the phosphorylation of Hsp27 are increased in the myocardium of
      patients with DM. In H9c2 cells hyperglycemia leads to a decrease of the Hsp27
      expression and an increase in argpyrimidine content and phosphorylation of Hsp27,
      which was accompanied by the induction of oxidative stress and apoptosis. This
      study shows an association between diabetes and increased argpyrimidine
      modification of myocardial Hsp27, a protein which is involved in apoptosis,
      oxidative stress, and cytoskeleton stabilization.

PMID- 19384819
TI  - Influence of perinatal stress on the hormone content in immune cells of adult
      rats: dominance of ACTH.
AB  - Rat dams were stressed by total deprivation of food and water for 48 h just
      before or directly after delivery and the offspring were studied when adult. The
      immune cells' hormone content (ACTH, histamine, serotonin, and T(3)) was measured
      by immunocytochemical flow cytometry. The elevation of ACTH content in males was
      convincing in each cell type (lymphocytes, monocytes and granulocytes, and mast
      cells). The change in histamine and T(3) content was inconsistent, while
      serotonin level did not change at all. As ACTH is the key hormone in the General
      Adaptation Syndrome, it seems likely that the perinatal stress primarily caused
      elevation in ACTH level and it was provoking the life-long hormonal imprinting.
      There was a difference between the reaction of males and females (with males'
      advance), which points to the gender dependence of the phenomenon. It is
      important that the effect of stress on the offspring was similar in case of
      direct (prenatal, in the mother) and indirect (postnatal, transmitted by milk)
      stress treatment, which calls attention to the danger of stress during this
      latter period.

PMID- 19384821
TI  - [Natural orifice transluminal endoscopic surgery (NOTES) hat sich zum stimulus
      fur viele alte und neue Ideen der minimalinvasiven Chirurgie und Endoskopie
      entwickelt. Die Umsetzung vieler Visionen hangt sehr von der zukunftigen
      technischen Entwicklung ab].

PMID- 19384820
TI  - Important role of TNF-alpha in inhibitory effects of Radix Sophorae Flavescentis
      extract on vascular restenosis in a rat carotid model of balloon dilatation
      injury.
AB  - The aim of this study was to determine the molecular mechanism underlying the
      inhibition of vascular restenosis by Radix Sophorae Flavescentis (RSF) extract
      after balloon dilatation injury. In a rat carotid model of balloon dilatation
      injury, the RSF extract showed a significant inhibitory effect on vascular
      restenosis. Immunohistochemistry showed that the expression of tumor necrosis
      factor-alpha (TNF-alpha) in the vascular focus was markedly reduced upon
      treatment with the RSF extract, whereas the expression of proliferating cell
      nuclear antigens (PCNA) was mostly unaffected. Colorimetric assays of methylene
      blue incorporation demonstrated that the proliferation of cultured vascular
      smooth muscle cells (VSMCs) was not inhibited with serum from rats treated with
      RSF extract. However, the expression of TNF-alpha in cultured VSMCs was
      significantly downregulated by serum from rats treated with RSF extract. These
      results suggested that RSF extract has an inhibitory effect on vascular
      restenosis after balloon dilatation injury which might be, in part, attributable
      to its inhibition of TNF-alpha expression.

PMID- 19384822
TI  - [1 case--2 statements by BGH on hypothetical patient education--requirements of
      BHG covered?].

PMID- 19384823
TI  - Walking track analysis: an assessment method for functional recovery after
      sciatic nerve injury in the rat.
AB  - Walking track analysis was first described by de Medinaceli et al. This technique
      has been significantly modified to provide methods of indexing nerve function
      that are more valid. Moreover, it has been questioned by several authors. The aim
      of the present review is to offer a combined knowledge about walking track
      analysis for scientists who deal with neuroscience.

PMID- 19384824
TI  - Anatomy of the posterior cruciate ligament.
AB  - The purpose of the study was to explain the architecture of the posterior
      cruciate ligament because the views on its structure presented in the literature
      are inconsistent - from those considering it as indivisible to those presenting
      it as a multifascicular structure. Twenty formalin-fixed ligaments from human
      knee joints were tested using the preparation technique. All posterior cruciate
      ligaments clearly divided into the anterolateral bundle and the posteromedial
      bundle (20/20). In all ligaments, 2 fascicles were identified in the
      posteromedial bundle (20/20). In most cases, 2 fascicles were also seen in the
      anterolateral bundle (14/20). Less commonly, it consisted of multiple fascicles
      (6/20).

PMID- 19384825
TI  - Topographical anatomy and morphometry of the temporal bone of the macaque.
AB  - Based on the dissections of 24 bones of 12 macaques (Macaca mulatta), a
      systematic anatomical description was made and measurements of the chosen size
      parameters of the temporal bone as well as the skull were taken. Although there
      is a small mastoid process, the general arrangement of the macaque's temporal
      bone structures is very close to that which is observed in humans. The main
      differences are a different model of pneumatisation and the presence of
      subarcuate fossa, which possesses considerable dimensions. The main air space in
      the middle ear is the mesotympanum, but there are also additional air cells: the
      epitympanic recess containing the head of malleus and body of incus, the mastoid
      cavity, and several air spaces on the floor of the tympanic cavity. The vicinity
      of the carotid canal is also very well pneumatised and the walls of the canal are
      very thin. The semicircular canals are relatively small, very regular in shape,
      and characterized by almost the same dimensions. The bony walls of the labyrinth
      are relatively thin.

PMID- 19384826
TI  - Distribution of cocaine- and amphetamine-regulated transcript in the hippocampal
      formation of the guinea pig and domestic pig.
AB  - This study provides a detailed description concerning the distribution of
      cocaineand amphetamine-regulated transcript (CART) subunits - CART(61-102) and
      rhCART(28-116) - in the hippocampal formation (HF) of the guinea pig and domestic
      pig, focussing on the dentate gyrus (DG) and hippocampus proper (HP). Although in
      both studied species CART-immunoreactive (CART-IR) neuronal somata and processes
      were present generally in the same layers, some species-specific differences were
      still found. In the granular layer (GL) of both species, the ovalshaped neurons
      and some thick varicose fibres were encountered. In the guinea pig there was an
      immunoreactive "band of dots", probably representing crosssectioned terminals
      within the DG molecular layer (MOL), whereas in the domestic pig, some varicose
      fibres were detected, thus suggesting a different orientation of, at least, some
      nerve terminals. Furthermore, some CART-positive cells and fibres were observed
      in the hilus (HL) of the guinea pig, whereas in the analogical part of the
      domestic pig only nerve terminals were labelled. In both species, in the
      pyramidal layer (PL) of the hippocampus proper, CART-IR triangular somata were
      observed in the CA3 sector, as well as some positive processes in MOL; however, a
      few immunoreactive perikarya were found only in the CA1 sector of the guinea pig.
      As regards the localization patterns of two isoforms of CART in the guinea pig,
      both peptide fragments were present simultaneously in each of the labelled
      neurons or fibres, whereas in the domestic pig three types of fibres may be
      distinguished within the area of the DG. In the hilus and MOL of the dentate
      gyrus, there were fibres expressing both isoforms of CART in their whole length
      (fibres of the first type). Fibres of the second type (in GL) coexpressed both
      peptides only on their short segments, and the last ones (in MOL) expressed
      solely rhCART(28-116). These results indicate that the distribution of the two
      CART isoforms are specifically related, thus the relationship between the two
      CART isoforms may imply different metabolic profiles of CART-expressing neurons.

PMID- 19384827
TI  - Microscopic study of right fibrous annulus.
AB  - The term annulus fibrous is still used in anatomical and clinical terminology but
      does not exist in anatomical nomenclature. This structure is proposed as an
      anatomical substrate for circus movement of excitation. Multiple cardiac damage
      after blunt chest trauma is rare, but usually affects the septal part of the
      right fibrous annulus. Histological observation confirms the results of our
      previous macroscopic study and shows that the most stable part of fibrous annulus
      is the septal part and the region of anterior angle of the right ventricle, and
      the most labile parts are the lateral and posterior angles of the right ventricle
      and the posterior part of the fibrous annulus. Our histological study shows that
      the right fibrous annulus is a heterogeneous structure and may play a role in
      changes of shape of the right atrio-ventricular ostium during human life.

PMID- 19384828
TI  - The heart and its valves in Caspian miniature horse: a topographic study.
AB  - The Caspian miniature horse is one of the rare small breeds in the north of Iran.
      In the present study, the position of the heart and its valves were determined
      topographically in 4 miniature horses. We found that Caspian miniature horses
      have general similarities, with certain topographical variability, with other
      horses.

PMID- 19384829
TI  - Ultrastructural organisation and functional aspects of the olfactory epithelium
      of Wallago attu (Bleeker).
AB  - The topological architecture and functions of different cells of the olfactory
      epithelium in Wallago attu (Bleeker) have been systematically studied using a
      scanning electron microscope. The elongated olfactory rosette of the fish
      consists of 62 to 64 primary lamellae in each left and right rosette. Each
      lamella is provided with apical sensory epithelium and basal non-sensory
      epithelium. Topological analysis reveals that sensory epithelium contains
      receptor cells, ciliated supporting cells, labyrinth cells, and goblet cells. The
      non-sensory epithelium is made up of patches of ciliated supporting cells,
      epidermal or stratified epithelial cells with concentrically arranged
      microridges, and scattered goblet cells. Different cells on the olfactory
      epithelium support the view that the olfactory signalling is important to the
      survival of this fish in an aquatic environment.

PMID- 19384830
TI  - Evaluation of androgenic activity of allium cepa on spermatogenesis in the rat.
AB  - Allium cepa (onion) has a beneficial effect on disease treatment worldwide and
      has been used since ancient times as a medicinal and food source. Recently
      several reports have shown that onion has high antioxidant activity. As
      antioxidants have an essential effect on sperm health parameters, we investigated
      the effect of the fresh juice of onion bulbs on the spermatogenesis cycle in
      rats. Wistar male rats (n = 30) were allocated into 3 groups, control (n = 10)
      and two test groups (each of 10). The animals in the test groups were subdivided
      into groups of 2 that received fresh onion juice equivalent to 0.5 and 1 g/rat/
      /day of fresh onion. The fresh onion juice was administered by gavage for 20
      consecutive days. The animals were kept in standard conditions. On the twentieth
      day, the testes of rats in all groups were removed and sperm was collected from
      the epididymis and was prepared for analysis. Serum total testosterone
      significantly increased in all the test groups (p < 0.05), and levels of LH
      significantly increased only in the group that received the high dose of fresh
      onion juice (p < 0.05), but the level of FSH did not differ between the
      experimental and control groups. The percentage of sperm viability and motility
      in both test groups significantly increased (p < 0.05), but the sperm
      concentration significantly increased only in the group that received the high
      dose of freshly extracted onion juice (p < 0.05). It was evident that there was
      no difference on sperm morphology and testis weight in test groups compared to
      the control group. In our study, freshly prepared onion juice significantly
      affected the sperm number, percentage of viability, and motility; it seems that
      using 4 g/kg of freshly prepared onion juice is effective in sperm health
      parameters.

PMID- 19384831
TI  - A rare case of bilateral supernumerary heads of sternocleidomastoid muscle and
      its clinical impact.
AB  - The sternocleidomastoid muscle (SCM) functions as a landmark for physicians such
      as anatomists, orthopaedic surgeons, neurosurgeons, and anaesthesiologists, who
      intervene in the minor supraclavicular fossa located at the base of the neck. The
      variability of SCM anatomy may cause complications while trying to access the
      vital elements that are located in the minor supraclavicular fossa. This study
      aims to present a case of supernumerary heads of the sternocleidomastoid muscle
      and to discuss its clinical significance. The cervical region of an elderly male
      cadaver was dissected and the findings were recorded and photographed. On both
      sides, the SCM muscle had an additional sternal head, and simultaneously there
      were three additional clavicular heads, four in total. These additional heads,
      the sternal and the clavicular, reduced the interval between them causing
      significant stenosis of the minor supraclavicular fossa. Sternocleidomastoid
      muscle variations with regard to the number of its heads are very rare in the
      literature, but this variation may cause severe complications. The minor
      supraclavicular fossa is important for anaesthesiologists because of the anterior
      central venous catheterization approach. Physicians should be aware of this
      anatomical variation in order to prevent complications.

PMID- 19384832
TI  - A rare muscle anomaly: the supraclavicularis proprius muscle.
AB  - In the Dissection Team of the Second Chair of Anatomy at the School of Medicine
      of the University of Buenos Aires, Argentina, during the routine dissection of 78
      cadavers (corresponding to 156 supraclavicular fossae),10% formalin fixed, we
      found the supraclavicularis proprius muscle over the lower part of the left
      supraclavicular fossa in an adult Caucasian male cadaver. We described this rare
      muscular anomaly, the likelihood of finding this muscle, and its participation in
      supraclavicular nerve entrapment syndrome.

PMID- 19384833
TI  - Hydrogen sulfide: a new gaseous signal molecule and blood pressure regulator.
AB  - The gas hydrogen sulfide (H2S) is emerging as a novel regulator of important
      physiologic functions such as arterial diameter, blood flow and leukocyte
      adhesion. In addition, it may have antiinflammatory and antiapoptotic effects.
      H2S has recently attracted much interest as a potent vasorelaxative substance
      that may establish itself alongside another gaseous signal molecule, nitric oxide
      (NO). In contrast to NO, the major source of H2S in blood may be production by
      red blood cells or by vascular smooth muscle cells. H2S is produced from
      cysteine, involving the enzymes cystathionine beta-synthase and cystathionine
      gamma-lyase (CSE). The importance of CSE was recently demonstrated in a mouse
      lacking CSE which showed reduced H2S levels and developed hypertension and
      reduced endothelium-mediated vasorelaxation. These data establish H2S as a new
      and important biologic signal molecule and as a new regulator of vascular blood
      flow and blood pressure.

PMID- 19384834
TI  - Salt and its effect on blood pressure and target organ damage: new pieces in an
      old puzzle.
AB  - For centuries, salt has been regarded as essential to human health. Recent work,
      however, has provided further evidence that the current dietary intake of salt in
      Western societies is an important factor in the genesis of essential hypertension
      and may even partly cause blood pressure-independent target organ damage
      including renal damage. Accordingly, recent guidelines recommend reduction of
      daily consumption of salt to 6 g/day. Individuals vary with respect to the
      increase of blood pressure with increasing salt intake (salt sensitivity);
      individuals with renal disease are particularly salt sensitive. Salt causes major
      alterations of renal hemodynamics and accelerates progression. Despite some
      opinions to the contrary, salt restriction and volume control is particularly
      important in dialyzed patients. Understanding of how salt affects blood pressure
      and renal function has recently been advanced in 2 respects. The past concept
      that salt acts by expanding the extracellular fluid space has been challenged by
      the demonstration of water-free sodium storage of salt in tissues. Furthermore,
      salt promotes the secretion of cardiotonic steroids, i.e., mammalian "digitalis."
      Initial observations suggest a causal role for cardiotonic steroids in the
      genesis of cardiac abnormalities in advanced renal disease.

PMID- 19384835
TI  - Sympathetic activation in cardiovascular and renal disease.
AB  - Given the importance of adrenergic neural functioning in cardiovascular control,
      the hypothesis that an elevation in sympathetic drive represents a key
      pathophysiological feature of diseases characterized by an impairment in cardiac
      or renal function has been long considered. However, modern approaches to
      directly quantify sympathetic nerve firing in humans have only been possible in
      the last 2 decades to provide objective documentation for the hypothesis. This
      paper will review the evidence that conditions such as essential hypertension,
      congestive heart failure and metabolic syndrome are all accompanied by an
      increased sympathetic drive, which is likely in all of them to play a
      pathogenetic role. It will then offer examples showing that sympathetic
      influences are directly involved in the progression of organ damage associated
      with these conditions. Finally, evidence will be presented that a maximum degree
      of sympathetic activation can be seen in end-stage renal failure, in which a
      relationship between sympathetic activation and clinical outcome has been
      documented. This has therapeutic implications, which involve the need to use
      treatments that oppose rather than enhance sympathetic neural activation.

PMID- 19384836
TI  - Disturbances of glomerular hemodynamics: a risk factor determing progression of
      glomerular diseases?
AB  - In this review, we introduce first our experimental rat model in which
      disturbances of vascular regeneration and glomerular hemodynamics lead to
      irreversible glomerulosclerosis. Secondly, we demonstrate a pivotal role for gap
      junctional intercellular communication and adenosine triphosphate-dependent
      intercellular communication, via Ca++ signaling, in coordinating behavior of
      mesangial and juxtaglomerular cells. This has deepened our understanding of
      regulatory glomerular hemodynamics at the cellular and molecular levels. Thirdly,
      we show that local delivery of renoprotective agents such as angiotensin II
      receptor blockers, in combination with a diagnostic imaging system of the renal
      microvasculature, allowed us to evaluate the therapeutic effects of local
      blockade of renin-angiotensin system activity on the progression of
      glomerulosclerosis, finally leading to renal death.

PMID- 19384837
TI  - Nephrogenic systemic fibrosis an unsolved riddle.
AB  - Nephrogenic systemic fibrosis (NSF) is an emergent scleroderma-like disease
      progressively inducing a skin and joint severe dermal fibrosis. Until now there
      have been about 215 cases reported in NSF registry, linked to the use of
      Gadolinium as contrast agent for Magnetic Resonance. The pathogenesis of NSF is
      unexplained, and the factor or factors triggering the onset of the disease are a
      matter of debate. The toxic Gd effect on tissues of uremic patients may be linked
      to the long Gd half-life. Alternatively, according to the transmetallation
      theory, Gd may easily be released from linear versus cyclic chelating agents
      exchanged with other metals. Despite many studies indicating exposure to Gd in
      end-stage renal disease (ESRD) or hemodialysis as a trigger of NSF, a certain
      cause-effect relationship has still not been found. Other epidemiological studies
      report cases of NSF without previous Gd infusion. Another intriguing hypothesis
      is the possible role of lanthanum carbonate, which like Gd is a rare earth
      element. The lanthanum toxicity theory may explain the diffusion of Gd-induced
      NSF only in countries where the use of lanthanum carbonate was introduced some
      years ago (e.g., United States and northern Europe). In spite of the tight
      linkage reported between Gd infusion and NSF occurrence in ESRD and HD
      patients,the prevalence of this dermal severe disease ranges from 0.4 to 0.7%.
      Therefore the nephrologist, must keep this in mind and advise patients that the
      risk of renal impairement induced by iodinated contrast media infusion, is
      exceedingly more elevated than the occurrence of Gd-induced NSF which is below
      1%.

PMID- 19384838
TI  - Sympathetic hyperactivity and clinical outcome in chronic kidney disease patients
      during standard treatment.
AB  - BACKGROUND: Sympathetic hyperactivity has been associated with adverse clinical
      outcome and is common in patients with chronic kidney disease (CKD). Angiotensin
      converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB)
      have been shown to reduce sympathetic activity in CKD patients. The present study
      was performed to investigate whether sympathetic hyperactivity was related to
      clinical outcome in CKD patients treated with ACEi or ARB. METHODS: Muscle
      sympathetic nerve activity (MSNA) was measured in 66 nondiabetic patients (70%
      men) with CKD, median age 47 years (range 21-65) and mean estimated glomerular
      filtration rate (eGFR) 39+/-29 ml/min per 1.73 m2. Patients were followed up for
      a median 78 months (range 6-123), and subsequent clinical events were recorded.
      RESULTS: During follow-up, average blood pressure was 131+/-11 mm Hg systolic and
      83+/-6 mm Hg diastolic. Twenty-one events (4 deaths and 17 nonfatal
      cardiovascular events) occurred in 16 patients. MSNA among the group with events
      was 40+/-18 bursts/min, compared with 30+/-11 bursts/min in those with no events
      (p=0.009). An increase of MSNA of 10 bursts/min was related to an increased risk
      of an event (hazard ratio=1.6; 95% confidence interval, 1.0-2.8; p=0.08),
      independent of GFR and blood pressure. Age attenuated this relation. CONCLUSION:
      Sympathetic hyperactivity was associated with the composite of all-cause
      mortality and nonfatal cardiovascular events in CKD patients, despite treatment
      with ACEi or ARB. Further studies to investigate potential effects of additional
      sympatholytic therapy in these patients are warrented.

PMID- 19384839
TI  - The relationship between adiponectin levels and proinflammatory cytokines and
      left ventricular mass in dialysis patients.
AB  - INTRODUCTION: Adiponectin is increased in end-stage renal disease. However,
      efforts to clarify the cause of that increase and its clinical effects have been
      inconclusive. The aim of this study was to compare serum adiponectin levels of
      dialysis patients against healthy individuals and evaluate the relationship among
      adiponectin levels, IL-6, TNF- alpha and left ventricular mass index (LVMI).
      METHODS: Adiponectin, IL-6 and TNF- alpha measurements and echocardiographic
      evaluations were performed in 36 hemodialysis, 30 continuous ambulatory
      peritoneal dialysis (CAPD) patients and 22 healthy volunteers. Adiponectin, IL-6
      and TNF- alpha levels were measured by ELISA. RESULTS: Adiponectin was found to
      be higher in hemodialysis (52.78+/-18.01 ng/mL) and CAPD (52.96+/-17.53 ng/mL)
      groups than controls (28.36+/-13.20 ng/ mL; p=0.0003, p=0.0003, respectively). No
      difference was observed between the hemodialysis and CAPD groups. Adiponectin was
      positively correlated with IL-6 (r=0.293, p=0.02), TNF- alpha (r=0.458, p=0.0003)
      and LVMI (r=0.283, p=0.02). In the partial correlation analysis, by controlling
      for body mass index, the correlation between adiponectin and TNF- alpha (r=0.466,
      p=0.0003) persisted. When IL-6 was controlled with TNF- alpha, the relation
      between adiponectin and LVMI disappeared (r=0.145, p=0.30). In the linear
      regression analysis, with adiponectin as the dependent variable, and IL-6, TNF-
      alpha and body mass index as independent variables, a significant relationship
      was found between adiponectin and TNF- alpha (beta=0.488, p=0.001). CONCLUSIONS:
      Increased adiponectin seems to be associated with increased proinflammatory
      cytokines in dialysis patients, and this relationship suggests adiponectin may
      have a role in the development of left ventricular hypertrophy.

PMID- 19384840
TI  - Antiproteinuric effect of olmesartan in patients with IgA nephropathy.
AB  - BACKGROUND: IgA nephropathy is one of the most common primary
      glomerulonephritides, and the clinical course of almost 40% of the patients
      progresses to end-stage renal disease (ESRD) within 20 years. Angiotensin
      converting enzyme (ACE) inhibitors and/ or angiotensin II receptor blockers
      (ARBs) induce a marked renoprotective effect in nondiabetic chronic proteinuric
      nephropathies including IgA nephropathy. However, in Japan, ACE inhibitors and
      ARBs are not used for normotensive patients. The purpose of the present study was
      to evaluate the antiproteinuric effect of olmesartan, one of the ARBs, in
      normotensive patients with IgA nephropathy in Japan. METHODS: Olmesartan was
      given to 25 patients for 16 weeks. The initial dose was 5 mg and was increased
      stepwise to 10 mg, 20 mg and 40 mg. RESULTS: Final doses were 40 mg (n=11), 20 mg
      (n=5), 10 mg (n=7) and 5 mg (n=2). The change in urinary protein to creatinine
      ratio was -56.2%+/-22.8% at week 16. Creatinine clearance showed no changes
      throughout the study period. Blood pressure (systolic/diastolic) was 118.9+/-7.0
      / 76.8+/-7.4 mm Hg in the lead-in period and decreased to 107.0+/-10.1/66.3+/-7.8
      mm Hg at week 16. At the end of treatment with olmesartan, no correlation was
      observed between changes in the urinary protein to creatinine ratio and mean
      blood pressure based on investigation of dispersion diagrams. CONCLUSIONS:
      Olmesartan monotherapy showed robust reduction of urinary protein in normotensive
      IgA nephropathy patients, suggesting that this effect is independent of its blood
      pressure-lowering properties.

PMID- 19384841
TI  - Improved intradialytic stability during haemodialysis with blood volume
      controlled ultrafiltration.
AB  - BACKGROUND: Intradialytic morbid events (IMEs) during haemodialysis (HD),
      including symptomatic hypotension, are related to ultrafiltration (UF)-induced
      hypovolaemia. Blood volume monitoring and automatic feedback control of the UF
      rate were developed to limit the extent of hypovolaemia during dialysis. The
      present study investigated the effect of blood volume (BV)-controlled UF on the
      incidence of HD treatments with IMEs. METHODS: This prospective randomised
      crossover study included hypotension-prone patients, characterised by occurrence
      of IMEs in at least 33% of HD treatments during a 6-week screening phase. These
      patients underwent 2 treatment phases, each lasting 6 weeks, in randomised order.
      Each patient served as their own control, treated with standard HD in one phase
      and with BV-controlled UF in the other phase. RESULTS: Thirty-four patients from
      9 HD centres were enrolled; 26 could be included in the analysis population. In
      comparison with standard HD, BV-controlled UF reduced the percentage of HD
      sessions complicated by IME significantly from 40%+/-27% to 32%+/-25% (p=0.02). A
      lower frequency of HD sessions with IME could be observed in 46% of the patients.
      The frequency of treatments with symptomatic hypotension was reduced from 32%+/
      23% in standard HD to 24%+/-21% with BV-controlled UF (p=0.04). Changes in blood
      pressure and heart rate from start to end of the HD session were not different
      between the 2 treatment modes. CONCLUSIONS: This crossover study showed improved
      intradialytic stability with BV-controlled UF, compared with standard HD.

PMID- 19384842
TI  - The impact of pruritus on the quality of life of patients undergoing dialysis: a
      single centre cohort study.
AB  - BACKGROUND: Pruritus is common in dialysis patients, but no studies have
      addressed its impact on the patients' quality of life (QoL). OBJECTIVE: We sought
      to measure the impact of pruritus on the QoL of patients undergoing chronic
      hemodialysis (HHD) or peritoneal dialysis (PPD). METHODS: Pruritus intensity was
      measured on a 10-point visual analog scale. QoL was investigated with the 36-item
      Short Form of the Medical Outcomes Study questionnaire (SSF-336), the 12-item
      General Health Questionnaire (GHQ-12) and a dermatological questionnaire (Skindex
      29). RESULTS: One hundred and thirty-nine patients on HD and 30 on PD were
      recruited. Pruritus was found in 88/169 patients (52.1%),with no differences
      between HD and PD patients. Prevalence of poor sleep in patients with pruritus
      was higher than in those without (559% vs. 11%; p<0.001). Both physical and
      mental scores of SF-36 did not correlate with the presence and the intensity of
      pruritus. Pruritus intensity was significantly related to poor scores in all 3
      subscales of Skindex-29 (symptoms, social function and emotions). In the
      subscales of social function and emotions, worse scores were observed in patients
      undergoing HD and with minor psychiatric disorders (GHQpos). CONCLUSIONS:
      Pruritus had a high level of impact on all aspects of QoL and was a predictor of
      poor sleep. Type of dialysis and minor psychiatric disorders affect the emotional
      and social aspects of QoL.

PMID- 19384843
TI  - Mass-screening for early detection of renal disease: benefits and limitations of
      self-testing for proteinuria.
AB  - INTRODUCTION: Chronic kidney diseases are of growing importance for our health
      system. With regard to the high number of undetected cases, screening programs
      provide opportunities for an early to detect and treat patients. METHODS: With
      the support of local newspapers, we performed a mass screening of the citizens of
      Wurzburg, Germany. One hundred thousand dipsticks for proteinuria were
      distributed. Citizens were invited to self-test their urine and to report the
      results to the organizing centre. RESULTS: We received information for
      approximately 22% of the distributed dipsticks. Positive tests results numbered
      2,458 after removal of 309 positive results for pre-diagnosed renal diseases.
      From family doctors, we obtained data for control investigations of 856 dipstick
      positive subjects. In 104 of them, chronic proteinuria could be confirmed, due to
      essential hypertension (n=47), pyelo/interstitial nephritis (n=26), diabetic
      nephropathy (n=20), glomerulonephritis (n=4), nephrolithiasis (n=4),
      hypernephroma (n=2) and polycystic kidney disease (n=1). DISCUSSION: The benefit
      of self-testing was an unexpectedly high compliance, even in males. However, a
      great number of abnormal tests could not be confirmed by family doctors, possibly
      owing to the time variation in urine testing (early-morning urine in the self
      test vs. daytime testing by the physician), the high variability of urinary
      protein excretion and a large number of false-positive tests in the inexperienced
      participants. CONCLUSION: Mass screening for proteinuria with self-testing
      enhances the awareness of renal diseases and improves the chances for an early
      diagnosis and therapy. Limitations are the frequent overdiagnosis of proteinuria
      due to minimal colour changes in the dipsticks.

PMID- 19384844
TI  - How long is the warranty period for nil or low coronary artery calcium in
      patients new to hemodialysis?
AB  - BACKGROUND: Coronary artery calcification (CAC) is common in patients with
      advanced chronic kidney disease on dialysis. A sizeable proportion of patients
      has no or minimal CAC at the inception of dialysis, but it is unclear how long
      they remain free of it. METHODS: For the purpose of this study, 36 incident
      hemodialysis patients were submitted to sequential chest computed tomography to
      quantify CAC at baseline, 6, 12, 18 and 30 months. RESULTS: Among them, 15 had
      absent or minimal CAC score (CACS 0 to 30) and 21 had a CACS>30 at baseline.
      Overall, the median baseline CACS was 129 (interquartile range [IQR]=0-709) and
      it increased to 364 (IQR=8.3-1683) at study completion (182% increase). Among the
      15 patients with minimal CACS, only 3 progressed and the median CACS increase was
      20, as opposed to 15 of 21 patients with a baseline CACS>30 whose median
      progression was 431 (p<0.02). The 18 patients who had CACS progression were older
      (68.5 vs. 57.3 years, p=0.0081) and exhibited a poorer control of mineral
      metabolism (phosphorus 5.2 vs. 4.9 mg/ dL, p=0.048; corrected calcium x
      phosphorus product [CaxP] 49.3 vs. 46.2 mg2/dL2, p=0.001) than the patients
      without progression. On multivariable analysis, independent predictors of
      progression were baseline CACS (p=0.038) and time-averaged Cax;P (p=0.077).
      CONCLUSION: These data suggest that absent or low CAC at baseline is associated
      with minimal progression even up to 30 months. Careful management of mineral
      metabolism appears to be one of the main factors that limit progression of CAC.

PMID- 19384845
TI  - Albumin influences expression and function of the membrane transporter P
      glycoprotein in HK-2 human proximal tubular cells.
AB  - BACKGROUND: In proximal tubular cells exposed to albumin genes encoding membrane
      transporters were found to be up-regulated or down-regulated. P-glyco-protein
      (Pgp) is an efflux pump which transports a variety of compounds outside the cell.
      In the kidney, Pgp is located mainly on the luminal side of proximal tubular
      cells. The aim of this study was to assess whether albumin overload influences
      the expression and function of Pgp in HK-2 cells. METHODS: Tubular cells were
      cultured in the presence of albumin (20 mg/mL) for 24 and 72 hours. Pgp
      expression was evaluated by Western blot (WB). ABCB1 gene expression was assessed
      by RT-PCR. Pgp-mediated transport was measured by the rhodamine-123 (R-123) test.
      RESULTS: WB showed decreased protein expression (-7% after 24 hours and -65%
      after 72 hours, vs. controls). RT-PCR showed that gene expression decreased to
      66% after 72 hours of treatment. The fluorescence of HK-22 cells was 2.4-fold
      higher compared with controls (R-123) test. TNF-alpha restored Pgp expression and
      function. CONCLUSIONS: Tubular cells exposed to albumin present a decrease in
      both protein and gene expression of Pgp with impairment in transport function.
      The overexposure of tubular cells to toxic substrates due to Pgp transport
      failure represents a novel mechanism of tubular damage linked to proteinuria.

PMID- 19384846
TI  - New method to compute mixed water and electrolyte changes in hyponatremia: a
      preliminary report.
AB  - BACKGROUND: We developed a new method that diagnoses when either Na or water
      alone are altered during electrolyte abnormalities. The aim of this study is to
      describe the preliminary report of an original method which can give exact or
      useful calculations even in mixed disorders. METHODS: when NaCl is lost, the
      plasma Cl (PCl) to plasma Na (PNa) ratio falls from 0.75 (the normal value)
      toward zero, the ratio of plasma anions other than Cl (POAN) to PNa rises toward
      unity and POAN/PPCl toward infinity. With subscript 0 or normal values and
      subscript 1 for those during derangement, PCl1/PCl0 falls below unity, while POAN
      1 /POAN 0 rises above unity in these hyponatremic disorders. Based on these
      changes, we developed exact mathematical formulas to compute alterations in
      solvent and solutes. The boundary conditions of applicability were computer
      modeled. RESULTS: regression coefficients between true data fed oo the computer
      and those calculated with our formulas were 1.00 when the boundary conditions
      were entirely met (R2=1.00, <0.0001) and 0.93-0.96 (R2>0.94<0.99, <0.001) when
      the boundary conditions were allowed to extend beyond their limits of exclusive
      mathematical validity. The method was extended to patients whose data satisfied
      the boundary conditions. The results show that the computations satisfactorily
      predict the exact measurements obtained by the change in body weight (R2=0.61,
      <0.001). CONCLUSIONS: This new method represents useful adjunct in evaluating and
      treating hyponatremias. Although its validity is limited to rather strict
      boundary conditions, it represents an original way to evaluate mixed
      solvent/solute derangements.

PMID- 19384847
TI  - Calcimimetics normalize the phosphate-induced stimulation of PTH secretion in
      vivo and in vitro.
AB  - BACKGROUND: Hyperphosphatemia is a key pathogenic factor in the development of
      secondary hyperparathyroidism and precludes its treatment with vitamin D.
      Calcimimetics are therapeutic drugs demonstrated to lower parathyroid hormone
      (PTH) levels through an increase in the intracellular calcium of parathyroid
      cells. The mechanism by which high phosphate levels stimulate PTH secretion is
      related to its ability to prevent the elevation of intracellular calcium. The aim
      of this study was to assess whether calcimimetics are able to normalize the
      phosphate-induced stimulation of PTH secretion. METHODS: In vivo experiments
      studied PTH-calcium curves, and were carried out by hypocalcemic or hypercalcemic
      clamp, in normal rats and those with hyperphosphatemic renal failure treated with
      the calcimimetic NPS R-568. For in vitro studies, parathyroid glands from normal
      rats were incubated in normal (1 mM) and high (4 mM) phosphate media with
      calcimimetic. RESULTS: PTH-Ca curves showed that the calcimimetics produced a
      marked reduction in PTH secretion in both the hyperphosphatemic and control rats;
      maximal suppression of PTH was achieved with calcium of 0.9 mM vs. 0.7 mM,
      respectively. No effect was observed with calcium 0.6 mM. In vitro experiments
      showed that the addition of calcimimetic to medium with high phosphate
      concentration reduced PTH to values similar to those obtained from glands
      incubated in normal phosphate concentration. CONCLUSION: Calcimimetics overcome
      the stimulatory effect of high phosphate on PTH secretion in vivo and in vitro.
      Thus, calcimimetics should be effective in patients with secondary
      hyperparathyroidism whose phosphorus levels would contraindicate vitamin D
      treatment alone.

PMID- 19384848
TI  - A case of membranous nephropathy associated with chronic sinusitis.
AB  - Here we report a case of a 71-year-old Japanese woman with membranous nephropathy
      complicated with chronic sinusitis. The patient visited our hospital for
      treatment of edema and proteinuria, and was diagnosed as nephrotic syndrome with
      serum total protein 7.5 g/dL, albumin 2.2 g/dL and urine protein 3.7 g/day. Renal
      biopsy revealed membranous glomerulonephritis with tubulointerstitial nephritis.
      She had suffered from chronic sinusitis for several years. Laboratory tests
      showed that immunoglobulin G (IgG) and soluble interleukin-2 receptor (sIL-2R)
      were markedly increased (3,233 mg/dL and 5,110 U/mL, respectively) and Gallium
      scintigraphy showed abnormal accumulation to the paranasal sinus. After operation
      for chronic sinusitis, the levels of IgG and sIL-2R were decreased, and nephrotic
      syndrome was improved without any other specific treatments. It is known that
      various diseases, including membranous nephropathy and sinusitis, are caused by T
      cell dysfunction. Thus, we suspect the pathogenetic link between membranous
      nephropathy and chronic sinusitis in this case, most probably through T-cell
      dysfunction.

PMID- 19384849
TI  - Kidney graft loss associated with JC polyomavirus nephropathy.
AB  - This is the first case of documented treatment failure of JCV nephritis, despite
      a reduction of immunosuppressive agents and the use of antiviral therapy. We
      consistently detected high levels of JCV viremia, which correlated with the
      progressive deterioration of the graft and caused the final loss of the kidney,
      suggesting that JCV plays an etiological role in the onset of severe nephropathy
      in kidney transplant patients.

PMID- 19384850
TI  - Abstracts of the 6th International Congress of the Vascular Access Society -
      April 20-22, 2009, Rome, Italy.

PMID- 19384851
TI  - Parathyroid hormone inhibits phosphorylation of mitogen-activated protein kinase
      (MAPK) ERK1/2 through inhibition of c-Raf and activation of MKP-1 in osteoblastic
      cells.
AB  - Parathyroid hormone (PTH) regulation of mitogen-activated protein kinases (MAPK)
      ERK1/2 contributes to PTH regulation of osteoblast growth and apoptosis. We
      investigated the mechanisms by which PTH inhibits ERK1/2 activity in osteoblastic
      UMR 106-01 cells. Treatment with PTH significantly inhibited phosphorylated
      ERK1/2 between 5 and 60 min. Transient transfection of cells with a cDNA encoding
      MAPK phosphatase-1 (MKP-1) resulted in 30-40% inhibition of pERK1/2; however MKP
      1 protein levels were only significantly stimulated by PTH after 30 mins,
      suggesting another mechanism for the early phase of pERK1/2 inhibition. The
      active upstream kinase c-Raf phosphorylation at serine 338 (ser(338)) was
      significantly inhibited by PTH treatment within 5 min and transfection of the
      cells with constitutively-active c-Raf blocked PTH inhibition of pERK1/2.
      Inhibition of pERK1/2 and phosphor-c-Raf were seen when cells were treated with
      PTH(1-34) or PTH(1-31) analogues that stimulate cAMP, but not with PTH(3-34),
      PTH(7-34) or PTH(18-48) that do not stimulate cAMP. Stimulation of the cells with
      forskolin or 8BrcAMP also inhibited pERK1/2 and c-Raf.p338. Our results suggest
      that rapid PTH inhibition of ERK1/2 activity is mediated by PKA dependent
      inhibition of c-Raf activity and that stimulation of MKP-1 may contribute to
      maintaining pERK1/2 inhibition over prolonged time.

PMID- 19384852
TI  - Different roles for KIF17 and kinesin II in photoreceptor development and
      maintenance.
AB  - Kinesin 2 family members are involved in transport along ciliary microtubules. In
      Caenorhabditis elegans channel cilia, kinesin II and OSM-3 cooperate along
      microtubule doublets of the axoneme middle segment, whereas OSM-3 alone works on
      microtubule singlets to elongate the distal segment. Among sensory cilia,
      vertebrate photoreceptors share a similar axonemal structure with C. elegans
      channel cilia, and deficiency in either kinesin II or KIF17, the homologue of OSM
      3, results in disruption of photoreceptor organization. However, direct
      comparison of the two effects is confounded by the use of different species and
      knockdown strategies in prior studies. Here, we directly compare the effects of
      dominant-negative kinesin II and KIF17 expression in zebrafish cone
      photoreceptors. Our data indicate that dominant-negative kinesin II disrupts
      function at the level of the inner segment and synaptic terminal and results in
      cell death. In contrast, dominant-negative KIF17 has no obvious effect on inner
      segment or synaptic organization but has an immediate impact on outer segment
      assembly.

PMID- 19384853
TI  - Expression of stem cell pluripotency factors during regeneration in newts.
AB  - In this study, we present data indicating that mammalian stem cell pluripotency
      inducing factors are expressed during lens and limb regeneration in newts. The
      apparent expression even in intact tissues and the ensued regulation during
      regeneration raises the possibility that these factors might regulate tissue
      specific reprogramming and regeneration. Furthermore, these factors should enable
      us to understand the similarities and differences between animal regeneration in
      the newt and stem cell strategies in mammals. Developmental Dynamics 238:1613
      1616, 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19384854
TI  - DAX-1 and SOX6 molecular interplay results in an antagonistic effect in pre-mRNA
      splicing.
AB  - DAX-1 (DSS-AHC Critical Region on the X Chromosome-1) is a member of the nuclear
      hormone receptor superfamily that has an important role in steroidogenesis and
      gonadogenesis. To investigate the role of DAX-1 in the testis, a yeast two-hybrid
      screen was performed and SOX6, member of the Sry box (SOX) protein family, was
      cloned as candidate. The interaction was confirmed biochemically and expression
      of SOX6 overlapped with that of DAX-1 in the developing gonad, as well as in
      Sertoli cells of the adult testis. We show here that DAX-1 is able to inhibit
      splicing in in vivo and in vitro splicing assays, and this inhibition is relieved
      by the addition of SOX6. SOX6 appears to inhibit the interaction between DAX-1
      and the splicing machinery, thus providing a likely mechanism for functional
      interference. We conclude that DAX-1 and SOX6 proteins interact, have overlapped
      expression in the testis, and act antagonistically during pre-mRNA splicing.
      Developmental Dynamics 238:1595-1604, 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19384855
TI  - Embryogenesis and laboratory maintenance of the foam-nesting tungara frogs, genus
      Engystomops (= Physalaemus).
AB  - The vast majority of embryological research on amphibians focuses on just a
      single genus of frogs, Xenopus. To attain a more comprehensive understanding of
      amphibian development, experimentation on non-model frogs will be essential.
      Here, we report on the early development, rearing, and embryological analysis of
      tungara frogs (genus Engystomops, also called Physalaemus). The frogs Engystomops
      pustulosus, Engystomops coloradorum, and Engystomops randi construct floating
      foam-nests with small eggs. We define a table of 23 stages for the developmental
      period in the foam-nest. Embryos were immunostained against Lim1, neural, and
      somite-specific proteins and the expression pattern of RetinoBlastoma Binding
      Protein 6 (RBBP6) was analyzed by in situ hybridization. Due to their brief life
      cycle, frogs belonging to the genus Engystomops are attractive for comparative
      and genetic studies of development. Developmental Dynamics 238:1444-1454, 2009.
      (c) 2009 Wiley-Liss, Inc.

PMID- 19384856
TI  - The shroom family proteins play broad roles in the morphogenesis of thickened
      epithelial sheets.
AB  - Thickened epithelial sheets are found in a wide variety of organ systems and the
      mechanisms governing their morphogenesis remain poorly defined. We show here,
      through expression patterns and functional studies, that Shroom family proteins
      are broadly involved in generating thickened epithelial sheets. Through in situ
      hybridization, we report the temporal and spatial expression patterns of the four
      Shroom family members during early Xenopus development, from oocytes to tadpole
      stage embryos. Further, we show that Shroom1 and 2 mRNAs are maternally
      expressed, while Shroom3 and Shroom4 are zygotic transcripts. In addition,
      maternal Shroom1 and 2 mRNAs localize in the animal hemisphere of the Xenopus egg
      and early blastula. During later development, all four Shroom family proteins are
      broadly expressed in developing epithelial organs, and the epithelial cells that
      express Shrooms are elongated. Moreover, we show that ectopic expression of
      Shroom2, like Shroom3, is able to increase cell height and that loss of Shroom2
      function results in a failure of cell elongation in the neural epithelium.
      Together, these data suggest that Shroom family proteins play an important role
      in the morphogenesis of several different epithelial tissues during development.
      Developmental Dynamics 238:1480-1491, 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19384858
TI  - If we build it, they might come: an empirical investigation of supply and demand
      in the recruitment of rural psychologists.
AB  - Past research has established that practicing doctoral level psychologists tend
      to cluster in metropolitan areas, leaving the rural population gravely
      underserved. Discussions of this problem have assumed that psychologists hold
      negative attitudes toward rural work for many reasons, leading to a supply
      shortage. The present study attempts to examine the accuracy of this hypothesis
      by examining attitudes of current doctoral students in clinical psychology. Eight
      hundred eighty-four students responded to an online survey. Results indicate that
      attitudes toward rural practice were not overwhelmingly negative as predicted.
      Additionally, a significant number of respondents endorsed positive attitudes
      toward rural practice. A follow-up study was conducted to determine if the
      shortage of rural psychologists might be attributed to a lack of demand from
      rural employers. A search of three popular job resources revealed that few rural
      jobs were advertised, indicating weak demand for psychologists in rural areas.
      Results indicate that efforts to recruit psychologists to rural areas should be
      rethought, and increasing the visibility of available opportunities for
      psychologists should be made a priority.

PMID- 19384857
TI  - Toward defining the phosphoproteome of Xenopus laevis embryos.
AB  - Phosphorylation is universally used for controlling protein function, but
      knowledge of the phosphoproteome in vertebrate embryos has been limited. However,
      recent technical advances make it possible to define an organism's
      phosphoproteome at a more comprehensive level. Xenopus laevis offers established
      advantages for analyzing the regulation of protein function by phosphorylation.
      Functionally unbiased, comprehensive information about the Xenopus
      phosphoproteome would provide a powerful guide for future studies of
      phosphorylation in a developmental context. To this end, we performed a
      phosphoproteomic analysis of Xenopus oocytes, eggs, and embryos using recently
      developed mass spectrometry methods. We identified 1,441 phosphorylation sites
      present on 654 different Xenopus proteins, including hundreds of previously
      unknown phosphorylation sites. This approach identified several phosphorylation
      sites described in the literature and/or evolutionarily conserved in other
      organisms, validating the data's quality. These data will serve as a powerful
      resource for the exploration of phosphorylation and protein function within a
      developmental context. Developmental Dynamics 238:1433-1443, 2009. (c) 2009 Wiley
      Liss, Inc.

PMID- 19384859
TI  - Thermoregulatory sympathetic nervous system activity and diet-induced waist
      circumference reduction in obese Japanese women.
AB  - The present study is designed to investigate how and to what extent sympathovagal
      behavior in a balanced low-calorie diet relates to favorable changes of body
      mass, waist circumference, and/or metabolic risk factors. The study involved 28
      mildly obese women without clinical complications, who underwent an 8-week
      calorie restriction program using a 1,200-kcal daily diet with an adequate
      nutrient content; including two regular meals, and one formula meal replacement.
      All subjects were examined before and after the dietary intervention. We measured
      anthropometric parameters, blood pressure, and biochemical blood profiles for
      lipid metabolism. Autonomic nervous system activity was evaluated by heart rate
      variability power spectral analysis. The dietary intervention induced moderate,
      but significant reduction of waist circumference (-5.3% +/- 0.8%), body fat
      percentage (-5.8% +/- 0.8%), and body mass (-6.6% +/- 0.5%). Linear regression
      analysis showed that Deltavery low frequency (VLF) power reflecting energy
      metabolic- and thermoregulatory sympathetic function significantly correlated to
      Deltawaist circumference (r = -0.53, P < 0.01), Deltabody fat percentage (r = 
      0.39, P < 0.05), Deltabody mass (r = -0.43, P < 0.05), DeltaHDL-cholesterol/total
      cholesterol ratio (HDL-C/TC) (r = 0.62, P < 0.001), and Deltanonesterified fatty
      acids (NEFA) (r = 0.56, P < 0.01). A stepwise multiple regression analysis
      additionally revealed that Deltawaist circumference (P = 0.024), DeltaHDL-C/TC (P
      = 0.013), and DeltaNEFA (P = 0.016) were significant and independent factors,
      which contributing to the variance in DeltaVLF power (r(2) = 0.61). Although
      causes and consequences of obesity continue to elude researchers, the present
      study indicates that thermoregulatory sympathetic activity relates to moderate
      waist-circumference reduction together with favorable changes of blood lipid
      profiles after short-term dietary modification in mildly obese women.

PMID- 19384860
TI  - Richer milk for sons but more milk for daughters: Sex-biased investment during
      lactation varies with maternal life history in rhesus macaques.
AB  - Lactation represents the greatest postnatal energetic expenditure for human and
      non-human primate females, and the ability to sustain the costs of lactation is
      influenced by a mother's physical condition. This is especially true for young
      mothers that initiate reproduction shortly after adolescence. These mothers have
      fewer bodily reserves available for lactation and face tradeoffs between
      reproduction and their own growth. Milk synthesis among captive rhesus macaques
      (Macaca mulatta) was investigated at the California National Primate Research
      Center from 2005 to 2007 (N = 114). Rhesus macaques produced low energy density
      milk typical of the primate order, but there was substantial individual variation
      among mothers in both milk energy density and yield. As a consequence, the
      available milk energy (AME), the product of milk energy density and milk yield,
      to support infant growth, development, and activity, varied tenfold among
      mothers. Primiparous mothers (N = 40) had fewer bodily resources, as measured by
      mass and body mass index, available for lactation than did multiparous mothers (N
      = 74) and showed poorer lactational performance. Mothers of sons produced milk of
      higher energy density, especially primiparous mothers, but lower milk yield, such
      that AME was the same for sons and daughters. Although AME from the mother was
      the same for sons and daughters, there was significant sexual dimorphism in
      infant mass. These data indicate that selection has likely favored sex-specific
      regulation of growth and development that is not necessarily contingent on
      greater maternal investment.

PMID- 19384861
TI  - The Garifuna (Black Carib) people of the Atlantic coasts of Honduras: Population
      dynamics, structure, and phylogenetic relations inferred from genetic data,
      migration matrices, and isonymy.
AB  - The aim of this study is to assess population dynamics, structure, and
      phylogenetic relations of the populations that inhabit the Caribbean coasts of
      Honduras: the Garifuna (or Black Carib) people, an admixture of Black Africans
      and Red Carib Native Amerindians. Thirteen autosomal tetranucleotide
      microsatellite markers of the DNA (namely short tandem repeats) were genotyped in
      samples from the Garifuna communities of Bajamar, in the Department of Cortes;
      Corozal, in the Department of Atlantida; and Iriona, in the Department of Gracias
      a Dios. Each subject in the study filled a questionnaire with the following
      information: complete name and surname of participant, and places of birth of the
      participant, his/her parents, and grandparents. We performed analyses that
      included determination of migration rates and residence patterns from information
      of places of birth, fixation indices from genetic data, and analysis of surnames
      of the sampled subjects (isonymy). Migration matrices showed a migration wave
      from east to west in the parents and grandparents of the subjects. A raise in
      migration rates and a shift in predominating residence pattern from neolocality
      to matrilocality from grandparents to parents were observed. Analysis of isonymy
      conjunctly with values for F(IS) in each community showed high endogamy in
      Bajamar, and recent, high immigration in Iriona. A dendrogram constructed with
      allele frequencies of the Garifuna and other populations from the Americas,
      Africa, and Europe revealed the close relationships of this ethnic group with
      Afro-Caribbean and African Populations.

PMID- 19384862
TI  - Fetal signaling through placental structure and endocrine function: illustrations
      and implications from a nonhuman primate model.
AB  - The placenta is a transmitter of fetal need and fetal quality, interfacing
      directly with maternal physiology and ecology. Plasticity of placental structure
      and function across the developmental timeframe of gestation may serve as an
      important tool by which a fetus calibrates its growth to shifting maternal
      ecology and resource availability, and thereby signals its quality and
      adaptability to a changing environment. Signals of this quality may be conveyed
      by the size of the placental interface, an important marker of fetal access to
      maternal resources, or by production of placental insulin-like growth factor-II,
      a driver of fetoplacental growth. Litter size variation in the common marmoset
      monkey offers the opportunity to explore intrauterine resource allocation and
      placental plasticity in an important nonhuman primate model. Triplet marmosets
      are born at lower birth weights and have poorer postnatal outcomes and
      survivorship than do twins; triplet placentas differ in placental efficiency,
      microscopic morphology, and endocrine function. Through placental plasticity,
      triplet fetuses are able to adjust functional access to maternal resources in a
      way that allows pregnancy to proceed. However, the costs of such mechanisms may
      relate to reduced fetal growth and altered postnatal outcomes, with the potential
      to lead to adverse adult health consequences, suggesting an important link
      between the placenta itself and the developmental origins of health and disease.

PMID- 19384863
TI  - Age at first reproduction and economic change in the context of differing kinship
      ecologies.
AB  - Kinship systems which tend to be based on ecologies of subsistence also assign
      differential power, privilege, and control to human connections that present
      pathways for manipulation of resource access and transfer. They can be used in
      this way to channel resource concentrations in women and hence their reproductive
      value. Thus, strategic female life course trade-offs and their timing are likely
      to be responsive to changing preferences for qualities in women as economic
      conditions change. Female life histories are studied in two ethnic groups with
      differing kinship systems in NE India where the competitive market economy is now
      being felt by most households. Patrilineal Bengali (599 women) practice
      patrilocal residence with village exogamy and matrilineal Khasi (656 women)
      follow matrilocal residence with village endogamy, both also normatively
      preferring three-generation extended households. These households have helpful
      senior women and significantly greater income. Age at first reproduction (AFR),
      achieved adult growth (height) and educational level (greater than 6 years or
      less) are examined in reproductive women, ages 16-50. In both groups, women
      residing normatively are older at AFR and taller than women residing
      nonnormatively. More education is also associated with senior women. Thus,
      normative residence may place a woman in the best reproductive location, and
      those with higher reproductive and productive potential are often chosen as
      households face competitive market conditions. In both groups residing in
      favorable reproductive locations is associated with a faster pace of fertility
      among women, as well as lower offspring mortality among Khasi, to compensate for
      a later start.

PMID- 19384864
TI  - Integration of proximate and evolutionary explanation of reproductive strategy:
      the case of callitrichid primates and implications for human biology.
AB  - We offer examples of how proximate and evolutionary forms of argument may inform
      each other in better understanding reproductive strategy in callitrichid
      primates, the smallest of the anthropoid primates. In addition, we illustrate how
      comparative approaches, when applied judiciously, can aid in the formulation of
      hypotheses regarding even seemingly unique traits within a taxonomic group. In
      the first example, examination of the nature of genetics in cytokine systems that
      leads to altered ovulation number in sheep suggests some relatively simple
      changes could explain both the adaptation of increased ovulation number in
      marmosets and the subsequent decrease in ovulation number in the closely related
      species, callimico. In the second example, the role of body size and phylogeny in
      explaining the role of maternal energy constraints upon gestation and lactation
      is explored, leading to additional hypotheses regarding these relations in a
      species that is both small but also in a phylogenetic line selected for slow
      reproduction. Finally, the role of comparative data in the study of proximate and
      evolutionary explanations of "unique" human reproductive strategies is discussed.

PMID- 19384865
TI  - Ritualized combat as an indicator of intrasexual selection effects on male life
      history evolution.
AB  - Trade-offs between survival, growth, current reproduction, and future
      reproduction influence life history evolution, leading to adaptive timing of
      investment in various strategies. If engagement in costly intrasexual contests to
      gain better access to mates is an important form of male reproductive investment,
      then the expression of characters that promote success in this process should be
      influenced by their fitness effects across the lifespan. To test this prediction,
      the ages at which human (Homo sapiens) males exhibit the greatest investment in
      morphological, behavioral, and physiological characters associated with
      intrasexual competition was estimated by examining the ages at which males
      succeed in a form of ritualized combat. The average age of international boxing
      champions was in the latter half of the twenties, and titles were held for about
      2 years on average. Thus, peak investment in traits that enhance intrasexual
      competition abilities appears to coincide with ages at which males have highest
      reproductive success. Additionally, larger males reached peak probability of
      success in this ritualized combat at ages about 2.6 years greater than smaller
      males. Because body size is highly heritable and there is strong positive
      assortative mating relative to this character among humans, this may indicate a
      polymorphic set of reproductive strategies produced through maintenance of
      coadapted gene complexes.

PMID- 19384866
TI  - Socioeconomic variation in the growth status of urban school children 6-13 years
      in Oaxaca, Mexico, in 1972 and 2000.
AB  - Socioeconomic variation in the growth status of urban school children 6-13 years
      of age in 1972 and 2000 was compared. The children were resident in the city of
      Oaxaca and were students in the same primary school in each year. Socioeconomic
      status (SES) was based on parental occupation. Height, sitting height, estimated
      leg length, weight, and the body mass index in 218 boys and 191 girls in 1972 and
      173 boys and 166 girls in 2000 were compared. Sex-specific MANCOVA was used to
      evaluate SES differences within each year, while sex- and SES-specific MANCOVA
      was used to evaluate differences between years. The prevalence of stunting,
      overweight and obesity was estimated. There were no SES differences among boys
      and girls in 1972 and boys in 2000; low-middle and middle SES girls were
      significantly taller and heavier with longer legs than low SES girls in 2000.
      Within each SES group, children in 2000 were significantly larger in body size
      and segment lengths except for sitting height in low SES children of both sexes.
      Estimated secular gains increased from low to low-middle to middle SES in both
      sexes. Inequitable gains by SES contributed to an increase in the magnitude of
      differences between SES groups, especially between low SES children on one hand
      and low-middle and middle SES children on the other hand. The prevalence of
      stunting declined while the prevalence of overweight and to a lesser extent in
      obesity increased from 1972 to 2000, more so in low-middle and middle SES than in
      low SES children.

PMID- 19384868
TI  - Binding of LBP-1a to specific immunoglobulin switch regions in vivo correlates
      with specific repression of class switch recombination.
AB  - Upon stimulation of mature B cells, class switch recombination (CSR) can alter
      the specific immunoglobulin heavy chain constant region that is expressed. In a
      tissue culture cell line, we previously demonstrated that inhibition of late SV40
      factor (LSF) family members enhanced IgM to IgA CSR. Here, isotype specificity of
      CSR regulation by LSF family members is addressed in primary mouse splenic B
      cells. First, we demonstrate that leader-binding protein-1a (LBP-1a) is the
      prevalent family member in B lymphocytes. Second, we demonstrate by ChIP that LBP
      1a binds genomic sequences around mouse switch (S) regions in an isotype-specific
      manner, in accordance with computational predictions: binding is observed to Smu
      and Salpha, but not to the tested Sgamma1, regions. Importantly, binding of LBP
      1a is tightly regulated, with occupancy at genomic S regions dramatically
      decreasing following LPS stimulation. Finally, the consequence of DNA-binding by
      LBP-1a is determined using bone marrow chimeric mice in which LSF/LBP-1 activity
      is inhibited in hematopoietic lineages. Upon in vitro stimulation of such primary
      B cells, CSR occurs with a higher efficiency to IgA, but not to IgG1. These
      results are supportive of a model whereby LBP-1a represses CSR in an isotype
      specific manner via direct interaction with S regions involved in the
      recombination.

PMID- 19384869
TI  - Functional TLR9 modulates bone marrow B cells from rheumatoid arthritis patients.
AB  - TLR9 recognizes unmethylated CpG-rich, pathogen-derived DNA sequences and
      represents the component of the innate immune system that heavily influences
      adaptive immunity and may contribute to the immunological disturbances in
      rheumatoid arthritis (RA). Accumulating data indicate that BM of RA patients
      participates in the pathogenesis of this disease as a site of proinflammatory
      cytokines overproduction and lymphocytes activation. Here, we investigated the
      functionality of TLR9 and its role in the modulation of RA BM B-cell functions.
      We report that BM B cells isolated from RA patients express TLR9 at the mRNA and
      protein levels acquired at the stage of preB/immature B-cell maturation.
      Stimulation of BM CD20(+) B cells by CpG-containing oligodeoxynucleotide-enhanced
      expression of activation markers (CD86 and CD54) triggered IL-6 and TNF-alpha
      secretion and cell proliferation. Significantly higher levels of eubacterial DNA
      encoding 16S-rRNA were found in BM samples from RA than osteoarthritis patients.
      Moreover, RA BM B cells exerted higher expression of CD86 than their
      osteoarthritis counterparts, suggesting their in situ activation via TLR9. Thus,
      our data indicate that TLR9 may participate in direct activation and
      proliferation of B cells in BM, and therefore could play a role in the
      pathogenesis of RA.

PMID- 19384870
TI  - Mice deficient in stem cell antigen-1 (Sca1, Ly-6A/E) develop normal primary and
      memory CD4+ and CD8+ T-cell responses to virus infection.
AB  - Stem cell antigen-1 (Sca1, Ly-6A/E) is a well-established marker of murine
      hematopoietic stem cells, and also is expressed on memory T cells. It has been
      suggested that the functional maintenance of T-cell memory requires the
      expression of Sca1 on a specialized population of memory T cells termed "memory
      stem cells". Here, we evaluate the requirement for Sca1 in the primary T-cell
      response to virus infection, and in the establishment and maintenance of T-cell
      memory. We find that Sca1 expression increases on almost all CD4(+) and CD8(+) T
      cells during virus infection, and remains high on virus-specific memory cells.
      However, Sca1-deficient (Sca1KO) mice generate normal primary T-cell responses to
      infection; the kinetics, the immunodominance hierarchy, and the absolute numbers
      of CD4(+) and CD8(+) T cells are essentially indistinguishable from those
      observed in WT mice. Furthermore, by several criteria, primary and memory T cells
      in Sca1-deficient mice are phenotypically and functionally normal. These data
      indicate that Sca1, although perhaps a useful marker of virus-specific memory T
      cells, is not required for the regulation of T-cell quantity or quality, or for
      the development of a competent pool of memory cells.

PMID- 19384871
TI  - Interleukin-10-secreting T cells define a suppressive subset within the HIV-1
      specific T-cell population.
AB  - Recent studies have indicated that Treg contribute to the HIV type 1 (HIV-1)
      related immune pathogenesis. However, it is not clear whether T cells with
      suppressive properties reside within the HIV-1-specific T-cell population. Here,
      PBMC from HIV-1-infected individuals were stimulated with a 15-mer Gag peptide
      pool, and HIV-1-specific T cells were enriched by virtue of their secretion of IL
      10 or IFN-gamma using immunomagnetic cell-sorting. Neither the IL-10-secreting
      cells nor the IFN-gamma-secreting cells expressed the Treg marker FOXP3, yet the
      IL-10-secreting cells potently suppressed anti-CD3/CD28-induced CD4(+) as well as
      CD8(+) T-cell proliferative responses. As shown by intracellular cytokine
      staining, IL-10- and IFN-gamma-producing T cells represent distinct subsets of
      the HIV-1-specific T cells. Our data collectively suggest that functionally
      defined HIV-1-specific T-cell subsets harbor potent immunoregulatory properties
      that may contribute to HIV-1-associated T-cell dysfunction.

PMID- 19384872
TI  - Prostaglandin E2 enhances Th17 responses via modulation of IL-17 and IFN-gamma
      production by memory CD4+ T cells.
AB  - The contribution of Th1 and Th17 cells in chronic inflammatory conditions leading
      to autoimmunity remains highly controversial. In inflamed tissues, production of
      prostaglandins by COX-2 has been proposed to favor Th17 responses indirectly by
      increasing IL-23 and blocking IL-12 release from APC. We report here that
      prostaglandin E2 (PGE2) can directly modulate cytokine production by human memory
      CD4(+) T cells. TCR triggering in the presence of PGE2 increased IL-17 and
      reduced IFN-gamma production by freshly isolated memory T cells or T-cell clones.
      PGE2 triggered the EP2 and EP4 receptors expressed on T cells leading to a rapid
      increase of retinoic-acid-related orphan receptor-gammat (ROR-gammat) and
      decrease of T-cell-specific T-box transcription factor 21 (T-bet) mRNA. Moreover,
      PGE2 promoted the selective enrichment of IL-17-producing cells by differentially
      modulating the proliferation of memory T-cell subsets in vitro. Taken together
      our results indicate that T-cell effector function is a direct target for PGE2
      modulation and suggest a novel mechanism by which inhibitors of prostaglandin
      synthesis, such as COX-2 inhibitors, exert their anti-inflammatory effect.

PMID- 19384873
TI  - Oncostatin M deficiency leads to thymic hypoplasia, accumulation of apoptotic
      thymocytes and glomerulonephritis.
AB  - Oncostatin M (OSM) has been implicated in immune regulation, though its precise
      role remains elusive. Here we show that OSM plays a crucial role in the
      prevention of autoimmune diseases. OSM-deficient mice showed normal development
      of T cells, B cells and DC; however, their thymus showed hypoplasia and altered
      medullary structure. Autoantibodies against dsDNA accumulated and
      glomerulonephritis developed in aged OSM-deficient mice. Apoptotic cells
      accumulated in the thymus of OSM-deficient mice, and the administration of
      dexamethasone in young OSM-deficient mice resulted in the massive accumulation of
      apoptotic thymocytes and production of autoantibodies. These results suggest that
      OSM plays a key role in the prevention of autoimmune disease by regulating the
      clearance of apoptotic thymocytes.

PMID- 19384875
TI  - Perspectives on human stem cell research.
AB  - Human stem cell research draws not only scientists' but the public's attention.
      Human stem cell research is considered to be able to identify the mechanism of
      human development and change the paradigm of medical practices. However, there
      are heated ethical and legal debates about human stem cell research. The core
      issue is that of human dignity and human life. Some prefer human adult stem cell
      research or iPS cell research, others hES cell research. We do not need to
      exclude any type of stem cell research because each has its own merits and
      issues, and they can facilitate the scientific revolution when working together.

PMID- 19384874
TI  - Gammadelta T cells in EAE: early trafficking events and cytokine requirements.
AB  - We have previously shown that gammadelta T cells traffic to the CNS during EAE
      with concurrently increased expression of beta(2)-integrins and production of IFN
      gamma and TNF-alpha. To extend these studies, we transferred bioluminescent
      gammadelta T cells to WT mice and followed their movement through the acute
      stages of disease. We found that gammadelta T cells rapidly migrated to the site
      of myelin oligodendrocyte glycoprotein peptide injection and underwent massive
      expansion. Within 6 days after EAE induction, bioluminescent gammadelta T cells
      were found in the spinal cord and brain, peaking in number between days 10 and 12
      and then rapidly declining by day 15. Reconstitution of gammadelta T cell(-/-)
      mice with gammadelta T cells derived from beta(2)-integrin-deficient mice (CD11a,
      -b or -c) demonstrated that gammadelta T-cell trafficking to the CNS during EAE
      is independent of this family of adhesion molecules. We also examined the role of
      gammadelta T-cell-produced IFN-gamma and TNF-alpha in EAE and found that
      production of both cytokines by gammadelta T cells was required for full
      development of EAE. These results indicate that gammadelta T cells are critical
      for the development of EAE and suggest a therapeutic target in demyelinating
      disease.

PMID- 19384876
TI  - Atomic layer deposition of platinum nanoparticles on carbon nanotubes for
      application in proton-exchange membrane fuel cells.

PMID- 19384877
TI  - Biosensing by densely packed and optically coupled plasmonic particle arrays.
AB  - Densely packed plasmonic particle arrays are investigated for biosensing
      applications. Such particle arrays exhibit interparticle optical coupling
      creating a strong field between the particles, which is useful for sensing
      purposes. The sensor properties, such as bulk sensitivity, layer sensitivity, and
      the depth of sensitivity are investigated with the aid of a multiple multipole
      program. Sensitivity to the analyte with low concentration is also examined by a
      dynamic adsorption processes. The detectable concentration limit of streptavidin
      within 3000 s in the detection system is expected from the signal-to-noise to be
      less than 150 pM.

PMID- 19384878
TI  - Bio/abiotic interface constructed from nanoscale DNA dendrimer and conducting
      polymer for ultrasensitive biomolecular diagnosis.
AB  - For sensors detecting immobilized biomarkers, the interface between the surface
      and the fluid medium plays an important role in determining the levels of signal
      and noise in the electrochemical detection process. When protein is directly
      immobilized on the metal electrode, denaturation of the protein by surface
      protein interaction results in low activity and low signal level. A conducting
      polymer-based interface can prevent the protein conformation change and alleviate
      this problem. A DNA dendrimer is introduced into the interfacial film on the
      sensor surface to further improve the sensor performance. DNA dendrimer is a
      nanoscale dendrite constructed of short DNA sequences, which can be easily
      incorporated into the abiotic conducting polymer matrix and is biocompatible with
      most biological species. In this work, DNA dendrimer and polypyrrole (DDPpy) form
      the bio/abiotic interface on electrochemical sensors. Detection of two salivary
      protein markers (IL-8 and IL-1beta) and one mRNA salivary marker (IL-8) is used
      to demonstrate the efficiency of the DDPpy sensor. A limit of detection (LOD) of
      protein of 100-200 fg mL(-1) is achieved, which is three orders of magnitude
      better than that without the DNA dendrimer interface. An LOD of 10 aM is
      established for IL-8 mRNA. The typical sample volume used in the detection is 4
      microL, thus the LOD reaches only 25 target molecules (40 yoctomole).

PMID- 19384880
TI  - Colloidal hollow spheres of conducting polymers with smooth surface and uniform,
      controllable sizes.

PMID- 19384879
TI  - Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted
      cancer therapy and dual optical/magnetic resonance imaging.
AB  - A biocompatible, multimodal, and theranostic functional iron oxide nanoparticle
      is synthesized using a novel water-based method and exerts excellent properties
      for targeted cancer therapy, and optical and magnetic resonance imaging. For the
      first time, a facile, modified solvent diffusion method is used for the co
      encapsulation of both an anticancer drug and near-infrared dyes. The resulting
      folate-derivatized theranostics nanoparticles could allow for targeted
      optical/magnetic resonance imaging and targeted killing of folate-expressing
      cancer cells.

PMID- 19384881
TI  - Polarization portraits of single multichromophoric systems: visualizing
      conformation and energy transfer.
AB  - A novel technique, two-dimensional (2D) polarization single-molecule imaging, is
      presented. It is based on measurements and analysis of fluorescence intensity as
      a function of excitation and emission polarization angles. The technique allows
      recording of full information on the steady-state polarization properties of
      fluorescent objects. It is particularly suitable for application to single
      multichromophoric systems (molecules or nanoparticles) with energy transfer (ET)
      between different chromophores (e.g., single fluorescent pi-conjugated polymer
      chains). The 2D polarization data simultaneously provide information on the
      conformation of the system and the efficiency of its internal excitation ET. The
      technique is used to characterize single chains and different kinds of chain
      aggregates of different conjugated polymers at different temperatures. The 2D
      polarization measurements reveal a dramatic difference in ET taking place in
      these systems. Clear temperature dependence of ET is observed for individual
      aggregates as well as for their statistical ensembles. Also, a dependence on
      solvent and aggregate size is shown. Additionally, extensive "traditional one
      dimensional" polarization results on the polarization anisotropy of fluorescence
      excitation and emission are presented. These results and findings are discussed
      in relation to internal organization of the nano-objects under study.

PMID- 19384882
TI  - Deformation measurements on thin clay tactoids.

PMID- 19384883
TI  - Encapsulation of multiple biological compounds within a single electrospun fiber.

PMID- 19384884
TI  - Generation of metal photomasks by dip-pen nanolithography.

PMID- 19384885
TI  - Polyaniline/Pt hybrid nanofibers: high-efficiency nanoelectrocatalysts for
      electrochemical devices.
AB  - A simple and facile procedure to synthesize a novel hybrid nanoelectrocatalyst
      based on polyaniline (PANI) nanofiber-supported supra-high density Pt
      nanoparticles (NPs) or Pt/Pd hybrid NPs without prior PANI nanofiber
      functionalization at room temperature is demonstrated. This represents a new type
      of 1D hybrid nanoelectrocatalyst with several important benefits. First, the
      procedure is very simple and can be performed at room temperature using
      commercially available reagents without the need for templates and surfactants.
      Second, ultra-high density small "bare" Pt NPs or Pt/Pd hybrid NPs are grown
      directly onto the surface of the PANI nanofiber, without using any additional
      linker. Most importantly, the present PANI nanofiber-supported supra-high density
      Pt NPs or Pt/Pd hybrid NPs can be used as a signal enhancement element for
      constructing electrochemical devices with high performance.

PMID- 19384886
TI  - Contingency learning in human fear conditioning involves the ventral striatum.
AB  - The ability to detect and learn contingencies between fearful stimuli and their
      predictive cues is an important capacity to cope with the environment.
      Contingency awareness refers to the ability to verbalize the relationships
      between conditioned and unconditioned stimuli. Although there is a heated debate
      about the influence of contingency awareness on conditioned fear responses,
      neural correlates behind the formation process of contingency awareness have
      gained only little attention in human fear conditioning. Recent animal studies
      indicate that the ventral striatum (VS) could be involved in this process, but in
      human studies the VS is mostly associated with positive emotions. To examine this
      question, we reanalyzed four recently published classical fear conditioning
      studies (n = 117) with respect to the VS at three distinct levels of contingency
      awareness: subjects, who did not learn the contingencies (unaware), subjects, who
      learned the contingencies during the experiment (learned aware) and subjects, who
      were informed about the contingencies in advance (instructed aware). The results
      showed significantly increased activations in the left and right VS in learned
      aware compared to unaware subjects. Interestingly, this activation pattern was
      only found in learned but not in instructed aware subjects. We assume that the VS
      is not involved when contingency awareness does not develop during conditioning
      or when contingency awareness is unambiguously induced already prior to
      conditioning. VS involvement seems to be important for the transition from a
      contingency unaware to a contingency aware state. Implications for fear
      conditioning models as well as for the contingency awareness debate are
      discussed.

PMID- 19384888
TI  - Dissociation between phase-locked and nonphase-locked alpha oscillations in a
      working memory task.
AB  - The functions of human alpha oscillations ( approximately 10 Hz) were related to
      cognitive processes such as memory and top-down control. Recent models suggest
      that alpha phase serves as a mechanism especially relevant for the timing of
      neural activity, whereas alpha amplitude is important for the inhibition of task
      irrelevant brain areas. This study investigates directly the influence of top
      down modulation on phase-locked and nonphase-locked alpha rhythms. We conducted
      an EEG experiment where subjects performed a working memory task. In the encoding
      phase of the task subjects had to learn presented pictures of nonliving objects
      that could later be asked to be retrieved. We varied the top-down modulation by
      including cues indicating either to remember or to forget (not to remember) the
      next following item. Spectral analyses showed that nonremember cues elicited
      pronounced alpha amplitude increase compared to remember cues. Furthermore, phase
      locking in low frequencies, especially in the alpha range (7-12 Hz), was stronger
      for remember as opposed to not-to-remember items. In conclusion, we propose that
      alpha amplitude reflects top-down modulated inhibition and that alpha phase is
      important for the exact timing of neural activity and can be related to binding
      processes.

PMID- 19384887
TI  - The fMRI success rate of children and adolescents: typical development, epilepsy,
      attention deficit/hyperactivity disorder, and autism spectrum disorders.
AB  - Functional magnetic resonance imaging (fMRI) in children is increasingly used in
      clinical application and in developmental research; however, little is known how
      pediatric patient and typically developing populations successfully complete
      studies. We examined pediatric success rates with epilepsy, attention
      deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and
      typically developing children (TYP). We also examined the affect of age, and, for
      ADHD populations, medication status on success rates. We defined a successful
      fMRI individual run when the data were interpretable and included in group
      statistics. For unsuccessful runs, datasets with excessive motion or floor task
      performance were categorized when possible. All clinical groups scanned less
      successfully than controls; medication status did not affect ADHD success
      (epilepsy, 80%; ADHD (off methylphenidate), 77%; ADHD (on methylphenidate), 81%;
      ASD, 70%; TYP, 87%). Ten to 18-year-old had a significantly greater scan success
      rate than 4- to 6-year-old; adolescents (13- to 18-year-old) demonstrated greater
      scan success rates than 7- to 9-year-old. Success rate for completing an entire
      battery of experimental runs (n = 2-6), varied between 50-59% for patient
      populations and 69% for TYP (79% when excluding 4- to 6-year-old). Success rate
      for completing one run from a battery was greater than 90% for all groups, except
      for ASD (81%). These data suggest 20-30% more children should be recruited in
      these patient groups, but only 10-20% for TYP for research studies. Studies with
      4- to 6-year-olds may require 20-40% additional participants; studies with 10- to
      18-year-olds may require 10-15% additional participants.

PMID- 19384889
TI  - Modulation of preparatory volitional motor cortical activity by paired
      associative transcranial magnetic stimulation.
AB  - Paired associative transcranial magnetic stimulation (PAS) has been shown to
      induce long-term potentiation (LTP)-like or long-term depression (LTD)-like
      change in excitability of human primary motor cortex (M1), as probed by motor
      evoked potential (MEP) amplitude. In contrast, little is known about PAS effects
      on volitional motor cortical activity. In 10 healthy subjects, movement related
      cortical potentials (MRCP) were recorded to index volitional motor cortical
      activity during preparation of simple thumb abduction (prime mover: abductor
      pollicis brevis, APB) or wrist extension movements (prime mover: extensor carpi
      radialis, ECR). PAS(LTP) increased, PAS(LTD) decreased, and PAS(control) did not
      change MEP(APB), while MEP(ECR), not targeted by PAS, remained unchanged in all
      PAS conditions. PAS(LTP) decreased MRCP negativity during the late
      Bereitschaftspotential (-500 to 0 ms before movement onset), only in the APB
      task, and predominantly over central scalp electrodes contralateral to the thumb
      movements. This effect correlated negatively with the PAS(LTP) induced increase
      in MEP(APB). PAS(LTD) and PAS(control) did not affect MRCP amplitude. Findings
      indicate a specific interference of PAS with preparatory volitional motor
      cortical activity, suggestive of a net result caused by increased M1 excitability
      and disrupted effective connectivity between premotor areas and M1.

PMID- 19384891
TI  - Oscillatory activity in parietal and dorsolateral prefrontal cortex during
      retention in visual short-term memory: additive effects of spatial attention and
      memory load.
AB  - We used whole-head magnetoencephalography to study the representation of objects
      in visual short-term memory (VSTM) in the human brain. Subjects remembered the
      location and color of either two or four colored disks that were encoded from the
      left or right visual field (equal number of distractors in the other visual
      hemifield). The data were analyzed using time-frequency methods, which enabled us
      to discover a strong oscillatory activity in the 8-15 Hz band during the
      retention interval. The study of the alpha power variation revealed two types of
      responses, in different brain regions. The first was a decrease in alpha power in
      parietal cortex, contralateral to the stimuli, with no load effect. The second
      was an increase of alpha power in parietal and lateral prefrontal cortex, as
      memory load increased, but without interaction with the hemifield of the encoded
      stimuli. The absence of interaction between side of encoded stimuli and memory
      load suggests that these effects reflect distinct underlying mechanisms. A novel
      method to localize the neural generators of load-related oscillatory activity was
      devised, using cortically-constrained distributed source-localization methods.
      Some activations were found in the inferior intraparietal sulcus (IPS) and
      intraoccipital sulcus (IOS). Importantly, strong oscillatory activity was also
      found in dorsolateral prefrontal cortex (DLPFC). Alpha oscillatory activity in
      DLPFC was synchronized with the activity in parietal regions, suggesting that
      VSTM functions in the human brain may be implemented via a network that includes
      bilateral DLPFC and bilateral IOS/IPS as key nodes.

PMID- 19384890
TI  - Co-speech gestures influence neural activity in brain regions associated with
      processing semantic information.
AB  - Everyday communication is accompanied by visual information from several sources,
      including co-speech gestures, which provide semantic information listeners use to
      help disambiguate the speaker's message. Using fMRI, we examined how gestures
      influence neural activity in brain regions associated with processing semantic
      information. The BOLD response was recorded while participants listened to
      stories under three audiovisual conditions and one auditory-only (speech alone)
      condition. In the first audiovisual condition, the storyteller produced gestures
      that naturally accompany speech. In the second, the storyteller made semantically
      unrelated hand movements. In the third, the storyteller kept her hands still. In
      addition to inferior parietal and posterior superior and middle temporal regions,
      bilateral posterior superior temporal sulcus and left anterior inferior frontal
      gyrus responded more strongly to speech when it was further accompanied by
      gesture, regardless of the semantic relation to speech. However, the right
      inferior frontal gyrus was sensitive to the semantic import of the hand
      movements, demonstrating more activity when hand movements were semantically
      unrelated to the accompanying speech. These findings show that perceiving hand
      movements during speech modulates the distributed pattern of neural activation
      involved in both biological motion perception and discourse comprehension,
      suggesting listeners attempt to find meaning, not only in the words speakers
      produce, but also in the hand movements that accompany speech.

PMID- 19384893
TI  - Flavonoid-matrix cluster ions in MALDI mass spectrometry.
AB  - The behaviour of 2,5-dihydroxybenzoic acid (2,5-DHB) matrix under matrix-assisted
      laser desorption/ionisation (MALDI) conditions was investigated, and the
      formation of 2,5-DHB cluster ions, mainly dehydrated 2,5-DHB ions, is reported.
      Interestingly, in the mass spectra of this compound, besides dimers and trimers,
      protonated tetramers, pentamers, hexamers and heptamers were also found with
      significant abundance.The MALDI behaviour of four flavonoids, quercetin,
      myricetin, luteolin and kaempferol, using 2,5-DHB as matrix, was also
      investigated. The mass spectra of the flavonoids studied revealed a number of
      flavonoid-2,5-DHB cluster ions (mainly with the dehydrated 2,5-DHB). The number
      of clusters formed is dependent on the structure of the analyte. For luteolin and
      kaempferol, in particular, evidence was found for the formation of cluster ions
      involving retro Diels Alder fragments and intact flavonoids molecules, as well as
      the corresponding protonated retro Diels Alder fragments with dehydrated DHB
      molecules. All ion compositions were attributed taking into account high accuracy
      mass measurements and tandem mass spectrometry experiments.

PMID- 19384892
TI  - Intra-articular gene delivery and expression of interleukin-1Ra mediated by self
      complementary adeno-associated virus.
AB  - BACKGROUND: The adeno-associated virus (AAV) has many safety features that favor
      its use in the treatment of arthritic conditions; however, the conventional,
      single-stranded vector is inefficient for gene delivery to fibroblastic cells
      that primarily populate articular tissues. This has been attributed to the
      inability of these cells to convert the vector to a double-stranded form. To
      overcome this, we evaluated double-stranded self-complementary (sc) AAV as a
      vehicle for intra-articular gene delivery. METHODS: Conventional and scAAV
      vectors were used to infect lapine articular fibroblasts in culture to determine
      transduction efficiency, transgene expression levels, and nuclear trafficking.
      scAAV containing the cDNA for interleukin (IL)-1 receptor antagonist (Ra) was
      delivered to the joints of naive rabbits and those with IL-1beta-induced
      arthritis. From lavage of the joint space, levels of transgenic expression and
      persistence were measured by enzyme-linked immunosorbent assay. Infiltrating
      leukocytes were quantified using a hemocytometer. RESULTS: Transgene expression
      from scAAV had an earlier onset and was approximately 25-fold greater than
      conventional AAV despite the presence of similar numbers of viral genomes in the
      nuclei of infected cells. Fibroblasts transduced with scAAV produced amounts of
      IL1-Ra comparable to those transduced with adenoviral and lentiviral vectors. IL1
      Ra was present in lavage fluid of most animals for 2 weeks in sufficient
      quantities to inhibit inflammation of the IL-1beta-driven model. Once lost,
      neither subsequent inflammatory events, nor re-administration of the virus could
      re-establish transgene expression. CONCLUSIONS: scAAV-mediated intra-articular
      gene transfer is robust and similarly efficient in both normal and inflamed
      joints; the resulting transgenic expression is sufficient to achieve biological
      relevance in joints of human proportion.

PMID- 19384894
TI  - Stringent testing identifies highly potent and escape-proof anti-HIV short
      hairpin RNAs.
AB  - BACKGROUND: RNA interference (RNAi) is a cellular mechanism that can be induced
      by small interfering RNAs to mediate sequence-specific gene silencing by cleavage
      of the targeted mRNA. RNAi can be used as an antiviral approach to silence the
      human immunodeficiency virus type 1 (HIV-1) through stable expression of short
      hairpin RNAs (shRNAs). Previously, we used a co-transfection assay in which shRNA
      constructs were transfected with an HIV-1 molecular clone to identify 20 shRNA
      inhibitors that target highly conserved HIV-1 sequences. METHODS: In the present
      study, we selected the most potent shRNAs to formulate a combinatorial shRNA
      therapy and determine the best and easiest method for antiviral shRNA selection.
      We performed transient inhibition assays with either a luciferase reporter or HIV
      1 molecular clone and also infected shRNA-expressing T cell lines with HIV-1 and
      monitored virus replication. The latter assay allows detection of viral escape.
      In addition, we also tested shRNA-expressing T cells upon challenge with
      increasing dosages of HIV-1, and measured the dose required to result in massive
      virus-induced syncytia formation in this 2-week assay. RESULTS: Extended
      culturing selected three highly effective shRNAs that do not allow viral
      replication for more than 100 days. This difference in potency was not observed
      in the transient co-transfection assays. The use of increased dosages of HIV-1
      selected the same highly potent shRNAs as the laborious and extended escape
      study. CONCLUSIONS: These highly potent shRNAs could be used for a clinical
      vector and the comparison of the developed assays might help other researchers in
      their search for antiviral shRNAs.

PMID- 19384895
TI  - 'By papers and pens, you can only do so much': views about accountability and
      human resource management from Indian government health administrators and
      workers.
AB  - Although accountability drives in the Indian health sector sporadically highlight
      egregious behaviour of individual health providers, accountability needs to be
      understood more broadly. From a managerial perspective, while accountability
      functions as a control mechanism that involves reviews and sanctions, it also has
      a constructive side that encourages learning from errors and discretion to
      support innovation. This points to social relationships: how formal rules and
      hierarchies combine with informal norms and processes and more fundamentally how
      power relations are negotiated. Drawing from this conceptual background and based
      on qualitative research, this article analyses the views of government primary
      health care administrators and workers from Koppal district, northern Karnataka,
      India. In particular, the article details how these actors view two management
      functions concerned with internal accountability: supervision and disciplinary
      action. A number of disjunctures are revealed. Although extensive information
      systems exist, they do not guide responsiveness or planning. While supportive
      supervision efforts are acknowledged and practiced, implicit quid-pro-quo
      bargains that justify poor service delivery performance are more prevalent.
      Despite the enactment of numerous disciplinary measures, little discipline is
      observed. These disjunctures reflect nuanced and layered relationships between
      health administrators and workers, as well as how power is negotiated through
      corruption and elected representatives within the broader political economy
      context of health systems in northern Karnataka, India. These various dimensions
      of accountability need to be addressed if it is to be used more equitably and
      effectively.

PMID- 19384896
TI  - Successful outcome of an idiopathic thrombosis of the fetal inferior vena cava.

PMID- 19384897
TI  - Relationship of p21-activated kinase (PAK) and filopodia to persistence and
      oncogenic transformation.
AB  - Previously, we found that oncogenically transformed cells had fewer filopodia and
      more large, p21-activated kinase (PAK)-dependent features than normal cells.
      These large protrusions (LPs) were increased in cells expressing RhoA(N19) with
      Cdc42-associated kinase (ACK). Here, we determine how GTPase-mediated mechanisms
      of focal contact (FC) regulation affect these protrusions. Constructs encoding
      various proteins were introduced into cells which were then studied by microscopy
      and computerized image processing and analysis. Constructs that prevented PAK
      recruitment by PAK-interacting exchange factor (PIX) or restricted PAK residence
      time on FCs decreased both protrusions. Thus, filopodia were also PAK-dependent.
      A comparison of FC distribution in cells expressing PAK in the presence or
      absence of PAK kinase inhibitor domain (KID) suggested that PAK enlarged FCs
      without affecting the prevalence of either protrusion. KID or Nck expression
      increased LPs but not filopodia. Nck failed to synergize with KID or ACK and
      RhoA(N19) in enhancing LPs. Nck and KID synergistically enhanced filopodia,
      possibly because Nck recruited PAK to FCs while KID prevented their dissociation
      by PAK-mediated autophosphorylation. Coexpression of Nck, ACK, and RhoA(N19)
      abrogated filopodia and replicated the transformed phenotype. Since Nck
      recruitment of PAK is implicated in persistence of directional movement, we
      studied the PAK-Nck interface. Filopodia were eliminated by the Nck PAK-binding
      domain and LPs by the PAK Nck-binding domain. The results suggested that
      filopodia formation has more stringent requirements than LP formation, and Nck
      and PAK are used differently in the protrusions. Loss of filopodia in transformed
      cells may reflect defective regulation of GTPase mechanisms.

PMID- 19384898
TI  - Over-expression of SUMO-1 induces the up-regulation of heterogeneous nuclear
      ribonucleoprotein A2/B1 isoform B1 (hnRNP A2/B1 isoform B1) and uracil DNA
      glycosylase (UDG) in hepG2 cells.
AB  - Sumoylation is one of the post-translational modifications that governs many
      cellular activities, including subcellular localization targeting, protein
      protein interaction, and transcriptional activity regulation. SUMO E3 ligases are
      responsible for substrate specificity determination in which PIAS is the largest
      E3 family that consists of five members in human; they are PIAS1, PIAS3, PIASx
      alpha, PIASx beta, and PIASy. Several studies showed that all these PIAS genes
      are highly expressed in testis but only a few reports have discussed their
      expression pattern in other tissues. Though liver is a multifunctional organ and
      one would expect to find regulation of cellular functions by sumoylation, the
      identified sumoylation substrates are scarce and few of them correlate with liver
      cancer. In this report, we have found that PIASx alpha, PIASx beta, and PIASy are
      highly expressed in liver as well as testis by tissue distribution studies. We
      thus aimed to identify any SUMO-1 related proteins in liver cancer cells by two
      dimensional gel electrophoresis and mass spectrometry. Two up-regulated proteins,
      heterogeneous nuclear ribonucleoprotein A2/B1 isoform B1 (hnRNP A2/B1 isoform B1)
      and uracil DNA glycosylase (UDG), have been identified in the EGFP-SUMO-1 over
      expressing HepG2 cells. The up-regulation is suggested to be mediated via changes
      at the translational level or protection from degradation by western blotting and
      RT-PCR.

PMID- 19384899
TI  - Cloning and sequencing of the biosynthetic gene cluster for saquayamycin Z and
      galtamycin B and the elucidation of the assembly of their saccharide chains.
AB  - Sweet ways: We have investigated the glycosyltransferase genes of the
      saquayamycin Z (shown) and galtamycin B biosynthetic gene cluster from
      Micromonospora sp. Tu6368. The results unambiguously show that both compounds are
      derived from the same cluster. Furthermore, the function of five
      glycosyltransferases was elucidated, and the results have shed light on the
      assembly of the sugar chains.The Gram-positive bacterium, Micromonospora sp.
      Tu6368 produces the angucyclic antibiotic saquayamycin Z and the tetracenequinone
      galtamycin B. The structural similarity of both compounds suggests a common
      biosynthetic pathway. The entire biosynthetic gene cluster (saq gene cluster) was
      cloned and characterized. DNA sequence analysis of a 36.7 kb region revealed the
      presence of 31 genes that are probably involved in saquayamycin Z and galtamycin
      B formation. Heterologous expression experiments and targeted gene inactivations
      were carried out to specifically manipulate the saquayamycin Z and galtamycin B
      pathways; this demonstrated unambiguously that both compounds are derived from
      the same cluster. The inactivation of glycosyltransferase genes led to the
      production of novel saquayamycin and galtamycin derivatives, provided information
      on the assembly of the sugar chains, and showed that tetracenequinones are formed
      from angucyclines.

PMID- 19384900
TI  - Unlocking the chemotherapeutic potential of beta-aminovinyl ketones and related
      compounds.
AB  - The role of beta-aminovinyl ketones as synthetic intermediates has been well
      categorised, but recent developments have shown an interesting array of
      applications and new chemotherapeutic potential, both in the preparation of
      biologically active heterocycles and as pharmacophores in their own
      right.Medicinal chemists are accustomed to using the products of Knoevenagel-type
      condensations as auxiliaries for the synthesis of N-containing heteroaromatic
      compounds. One such example of these chemical building blocks are beta-aminovinyl
      ketones-valuable synthetic intermediates that have been used in the preparation
      of pyridines, pyrimidines, pyrazoles, and many other heterocyclic motifs. This
      review highlights their recent use in the synthesis of biologically active
      targets as part of drug discovery programmes and in natural product synthesis.
      However, it is becoming increasingly evident that the enaminone motif may serve
      as a therapeutic pharmacophore in its own right. This review highlights the range
      of biological responses that beta-aminovinyl ketones elicit, including as
      antitumour, antibacterial, and anticonvulsant agents. Thus, with a broad spectrum
      of biological properties and as versatile chemical intermediates, it is clear
      that beta-aminovinyl ketones offer great potential in the search for new
      chemotherapeutic agents.

PMID- 19384901
TI  - Fragment formal concept analysis accurately classifies compounds with closely
      related biological activities.
AB  - Fragment formal concept analysis (FragFCA) for compound classification: Signature
      fragment combinations for compound classes with closely related biological
      activity were identified using FragFCA. These combinations are used to accurately
      classify active test compounds on the basis of fragment mapping. FragFCA can
      extract class-specific fragment combinations from compounds active against
      different target families that have signature character and practical utility in
      compound classification and database searching.Formal concept analysis (FCA),
      originally developed in information science, has been adapted to identify
      relationships between fragments of compounds and their biological activity. Here
      applications of the FragFCA approach with practical utility for medicinal
      chemistry are explored. Hierarchically derived fragment populations of 24 classes
      of compounds active against eight target families were subjected to FragFCA
      analysis, and fragment combinations were identified that distinguished compounds
      with closely related biological activity from each other. Mapping of signature
      fragment combinations was carried out to classify active compounds for different
      target families with high accuracy. The results indicate that compound-class
      specific structural information and selectivity determinants are predominantly
      encoded by fragment combinations, rather than individual fragments. Furthermore,
      class-specific fragment combinations were successfully applied in similarity
      searching. The results demonstrate that FragFCA is capable of identifying
      fragment combinations that differentiate between compound sets with closely
      related biological activity and that can be used to predict structure-activity
      relationships.

PMID- 19384902
TI  - Metal-promoted nucleophilic addition and cyclization of diamines with
      dicyanonitrosomethanide, [C(CN)2(NO)]-.
AB  - The metal-promoted nucleophilic addition of diaminoalkanes to
      dicyanonitrosomethanide, C(CN)2(NO)- (dcnm), and subsequent cyclization has been
      utilized in the synthesis of novel anionic species. The addition and cyclization
      of 1,2-diaminoethane (en) to both nitrile groups of dcnm forms the anion
      diimidazolinylnitrosomethanide (dinm), isolated in the dinuclear complex
      [{Cu(dinm)(en)}2en][ClO4]2 (1). The same reaction solution yields
      [Cu(cinm)(ainm)] (cinm=cyanoimidazolinylnitrosomethanide, ainm=(((2
      aminoethyl)amino)iminomethyl)imidazolinylnitrosomethanide) (2), which contains
      intermediates of the dinm species, supporting a stepwise mechanism of addition of
      the diamine followed by cyclization. 1,3-Diaminopropane (pn) added and cyclized
      on only one nitrile group to form a 1,4,5,6-tetrahydropyrimidine ring. This
      resulted in the formation of the cyanonitroso-1,4,5,6
      tetrahydropyrimidinylmethanide ligand (cnpm) in complexes with the general
      formula [M(cnpm)2(pn)] (M=Cu (3a), Ni (3b), Zn (3c)). These reactions are
      contrasted to the addition of ethanolamine in the pyridine (py) complex
      [Ni(chnm)2(py)2].(py) (4) (chnm=cyano((2
      hydroxyethyl)amino)iminomethylnitrosomethanide) with no cyclization,
      demonstrating the higher reactivity of amines compared with alcohols. The
      formation of the complexes [M(cmnm)2(mame)] (M=Co (5a), Ni (5b),
      cmnm=cyano(imino(methoxy)methyl)nitrosomethanide, mame=1-dimethylamino-2
      methylaminoethane) indicate mame may be too sterically hindered to add to dcnm
      under similar reaction conditions.

PMID- 19384903
TI  - Low concentration of lipopolysaccharide acts on MC3T3-E1 osteoblasts and induces
      proliferation via the COX-2-independent NFkappaB pathway.
AB  - The translocations of lipopolysaccharide (LPS) from the gut and its effects on
      bone healing are usually of clinical interest during bone fracture. As already
      widely studied, Cyclooxygenase-2 (COX-2) is a key enzyme for prostaglandin E2
      (PGE(2)) production, which induces the nuclear factor kappa B (NFkappaB)
      activation and is beneficial to fracture healing. In order to know their roles in
      skeletal regeneration, mouse MC3T3-E1 osteoblasts were treated with NFkappaB
      inhibitor BAY 11-7082 and sc791 (a selective COX-2 inhibitor), in the presence of
      LPS. Interestingly, LPS could induce osteoblasts proliferation through increasing
      NFkappaB activation and translocation. This induction was not related to COX-2
      expression, suggesting that LPS-induced NFkappaB activation is independent of COX
      2. It is possible that low concentration of LPS can act as a stimulating factor
      of the NFkappaB pathway in nonstimulated cells such as osteoblasts. COX-2 is not
      necessary for the NFkappaB pathway during LPS-induced proliferation of
      osteoblasts since sc791 had no effects on this induction. These studies provide
      insight into a potential mechanism by which LPS can affect bone tissue repair in
      the initial phase of inflammation.

PMID- 19384904
TI  - Promoter hypermethylation of tumor-related genes in peritoneal lavage and the
      prognosis of patients with colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: The predictive value of free cancer cells in the
      peritoneal fluid of patients with colorectal cancer (CRC) remain to be
      elucidated. The aim of this study was to determine the prognostic relevance of
      the methylation of tumor-related genes detected in the peritoneal lavage fluid
      (PLF) of patients undergoing a resection for CRC. METHODS: The promoter
      methylation pattern of four target genes, CDH1, CDKN2A (p16), MGMT, and APC, was
      examined in 51 primary CRC and corresponding matched PLF DNA. The relative
      methylation levels of these genes in primary CRC tissue and paired PLF were
      assessed by quantitative methylation-specific polymerase chain reaction (QMSP).
      RESULTS: An aberrant methylation of at least one gene was found in 45 of 51 (88%)
      primary tumors. In matched PLF specimens, the frequencies of aberrant promoter
      methylation detected for each marker were 16% for CDH1, 2% for p16, 4% for MGMT
      and 24% for APC. Patients with PLF demonstrating the methylation of more than one
      of these four target genes demonstrated significantly shorter relapse-free
      survival. CONCLUSIONS: These findings suggest that disseminated tumor cells in
      PLF detected by QMSP may correlate with the postoperative clinical course of
      patients undergoing curative surgery for CRC.

PMID- 19384906
TI  - Osteosarcoma in the elderly over 60 years: a multicenter study by the Japanese
      Musculoskeletal Oncology Group.
AB  - BACKGROUND: Few studies have described the characteristics and prognostic factors
      of osteosarcoma patients aged over 60 years. METHODS: The Japanese
      Musculoskeletal Oncology Group (JMOG) carried out a retrospective review of
      patients over the age of 60 years with osteosarcoma. RESULTS: Only 12 patients
      had secondary osteosarcoma, with none associated with Paget's disease. The
      primary disease sites were the extremities in 63% and trunk in 33%. The overall
      survival was 42.8% and disease-free survival was 40.8% at 5 years in the high
      grade group. An univariate analysis indicated that significant poor prognostic
      factors for overall survival were axial location, lung metastasis at initial
      presentation, and absence of surgical treatment. Multivariate analysis revealed
      that a significant poor prognostic factor for overall survival was the absence of
      surgical treatment. Secondary osteosarcoma did not lower the overall or the
      disease-free survival in any group. CONCLUSIONS: The current study indicates that
      the number of osteosarcoma patients over 60 years is increasing. The number of
      cases with secondary osteosarcoma over 60 years is relatively small in Japan,
      with no patients having osteosarcomas related to Paget's disease. Although there
      is a predilection for axial localization, surgical treatment has a significant
      impact on patient's prognosis.

PMID- 19384907
TI  - Lymph node involvement in ampullary cancer: the importance of the number, ratio,
      and location of metastatic nodes.
AB  - BACKGROUND AND OBJECTIVES: Lymph node involvement significantly affects survival
      of cancer patients. The aim of this study was to evaluate the importance of the
      number, ratio, and location of metastatic lymph nodes in ampullary cancers.
      METHODS: Medical records of 111 patients who underwent curative
      pancreaticoduodenectomy for ampullary carcinomas were reviewed. RESULTS:
      Metastatic lymph nodes were found in 52 (47%) patients and the median number of
      involved nodes was 3 (95% confidence interval (CI) 3-4; range 1-17). In the
      univariate analysis, gender, type of pancreaticoduodenectomy, depth of tumor
      invasion, perineural invasion, presence of metastatic nodes, their number, and
      ratio of metastatic nodes significantly correlated with patient survival.
      However, the location of metastatic nodes did not influence survival among
      patients with nodal involvement. Only four or more metastatic nodes (relative
      risk 7.35, 95% CI 3.34-16.17) and tumor invasion of peripancreatic soft tissues
      (relative risk 5.00, 95% CI 1.20-20.92) were the independent prognostic factors
      in the multivariate analysis. CONCLUSIONS: The number of metastatic nodes
      significantly affected patient survival. Although the location and ratio of
      metastatic nodes were not independent prognostic factors, these variables should
      be further evaluated with large-scale population data sets.

PMID- 19384905
TI  - The 4th dimension and adult stem cells: Can timing be everything?
AB  - The rotation of the earth on its axis influences the physiology of all organisms.
      A highly conserved set of genes encoding the core circadian regulatory proteins
      (CCRP) has evolved across species. The CCRP acts through transcriptional and post
      transcriptional mechanisms to direct the oscillatory expression of genes
      essential for key metabolic events. In addition to the light:dark cycle, the CCRP
      expression can be entrained by changes in feeding and physical activity patterns.
      While mammalian CCRP were originally associated with the central clock located
      within the suprachiasmatic nucleus of the brain, there is a growing body of
      evidence documenting the presence of the CCRP in peripheral tissues. It is now
      evident that the CCRP play a role in regulating the proliferation,
      differentiation, and function of adult stem cells in multiple organs. This
      concise review highlights findings concerning the role of the CCRP in modulating
      the adult stem cell activities. Although the manuscript focuses on hematopoietic
      stem cells (HSCs), bone marrow-derived mesenchymal stem cells (BMSCs), adipose
      derived stem cells (ASCs) and cancer stem cells, it is likely that the
      contribution of the CCRP merits consideration and evaluation in all stem cell
      pathways.

PMID- 19384908
TI  - Invasive intraductal papillary-mucinous neoplasm of the pancreas: comparison with
      pancreatic ductal adenocarcinoma.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to clarify the
      clinicopathological differences between patients with invasive intraductal
      papillary-mucinous neoplasm (IPMN) of the pancreas and pancreatic ductal
      adenocarcinoma. METHODS: The medical records of 16 patients with invasive IPMN
      and 106 patients with pancreatic ductal adenocarcinoma, who underwent surgical
      resection, were retrospectively reviewed, and the clinicopathological factors and
      survival were compared between the two groups. RESULTS: The presence of
      retroperitoneal tissue invasion, portal or splenic vein invasion, nodal
      involvement, and positive surgical margins were significantly lower in patients
      with invasive IPMN than in those with ductal adenocarcinoma (P < 0.05). The
      actuarial 5-year overall survival rates in patients with invasive IPMN and ductal
      carcinoma were 40% and 18%, respectively (P = 0.008). However, the actuarial 5
      year survival rate of patients with invasive IPMN was only 27% for UICC stage II
      disease, although this was significantly higher than that of patients with UICC
      stage II ductal adenocarcinoma (P = 0.049). CONCLUSIONS: Invasive IPMN has a
      favorable prognosis compared with pancreatic ductal adenocarcinoma that is likely
      due to the less aggressive nature of the disease. However, the prognosis for
      cases of advanced invasive IPMN is not always favorable despite complete tumor
      resection.

PMID- 19384909
TI  - Colonic ischaemia and intra-abdominal hypertension following open repair of
      ruptured abdominal aortic aneurysm.
AB  - BACKGROUND: The aim was to investigate the association between colonic ischaemia
      and intra-abdominal pressure (IAP) after surgery for ruptured abdominal aortic
      aneurysm (rAAA). METHODS: Sigmoid colon perfusion was monitored with an
      intramucosal pH (pHi) tonometer. Patients with a pHi of 7.1 or less were treated
      for suspected hypovolaemia with intravenous colloids and colonoscopy. IAP was
      measured every 4 h. Patients with an IAP of 20 mmHg or more had neuromuscular
      blockade, relaparotomy or both. RESULTS: A total of 52 consecutive patients had
      open rAAA repair; 30-day mortality was 27 per cent. Eight patients died shortly
      after surgery. Fifteen were not monitored for practical reasons; mortality in
      this group was 33 per cent. IAP and pHi were measured throughout the stay in
      intensive care in the remaining 29 patients. Monitoring led to volume
      resuscitation in 25 patients, neuromuscular blockade in 16, colonoscopy in 19 and
      relaparotomy in two. One patient died in this group. Twenty-three of 29 patients
      had a pHi of 7.1 or less, of whom 15 had a pHi of 6.9 or less. Sixteen had an IAP
      of 20 mmHg or more, of whom ten also had a pHi below 6.90. Peak IAP values
      correlated with the simultaneously measured pHi (r = -0.39, P = 0.003).
      CONCLUSION: Raised IAP is an important mechanism behind colonic hypoperfusion
      after rAAA repair. Monitoring IAP and timely intervention may improve outcome.

PMID- 19384910
TI  - Measurement of anal cushions in idiopathic faecal incontinence.
AB  - BACKGROUND: Faecal incontinence affects a heterogeneous population and aetiology
      can be multifactorial. In a subset of patients the aetiology remains idiopathic
      despite standard investigations. Anal cushions are important in normal
      continence, but have rarely been studied. The aim of this study was to measure
      the size of the anal cushions and to evaluate their role in patients with
      idiopathic faecal incontinence. METHODS: Women in whom idiopathic faecal
      incontinence was diagnosed after standard anorectal investigations underwent
      transvaginal ultrasonography. The area of the anal cushions was measured and a
      cushion : canal (C : C) ratio derived, which was compared with that in a control
      group of women without faecal incontinence. RESULTS: Some 21 patients with
      incontinence (median age 60 years) and 102 asymptomatic controls (median age 41
      years) underwent scanning. The median (interquartile range) C : C ratio in the
      symptomatic group was significantly lower than that for controls (0.57 (0.54
      0.66) versus 0.68 (0.61-0.73) respectively; P = 0.001). C : C ratio was not
      influenced by age (r = 0.023, P = 0.821). CONCLUSION: The C : C ratio was reduced
      in patients with idiopathic faecal incontinence.

PMID- 19384911
TI  - Enzyme catalysis "reilluminated".
AB  - In a new light: The NADPH:protochlorophyllide (Pchlide) oxidoreductase (POR; see
      structure, green Pchlide, yellow NADPH) is a good model to investigate
      catalytical processes in enzymes, as its light activation allows an immediate
      start of the catalyzed reaction. By irradiation with weak, short laser pulses it
      is possible to detect conformation changes during the reaction and thus to
      uncover the elementary steps of the catalytic process.

PMID- 19384912
TI  - Faecal calprotectin or lactoferrin can identify postoperative recurrence in
      Crohn's disease.
AB  - BACKGROUND: Identifying Crohn's disease recurrence in symptomatic patients after
      ileocaecal resection is difficult. The aim of this study was to evaluate faecal
      concentrations of granulocyte degradation products in this setting. METHODS: A
      postoperative cohort of 13 patients was followed prospectively for 1 year with
      regular faecal calprotectin (FC) and lactoferrin (FL) measurements. A second
      postoperative cohort (median 24 months after resection) of 104 patients provided
      a single stool sample. Faecal measurements were compared with symptom diaries,
      the Harvey Bradshaw Index, endoscopic examination, C-reactive protein and
      platelet measurement. RESULTS: In the uncomplicated course, both markers
      normalized within 2 months. Both FC and FL correlated significantly with Harvey
      Bradshaw Index (P < 0.001). Twenty-eight patients with severely clinically active
      disease had high mean(s.e.) levels of FC (661.1(119.1) microg/g) and FL
      (116.6(32.2) microg/g); and 43 with clinically inactive disease had low levels of
      FC (70.2(27.1) microg/g) and FL (5.9(2.4) microg/g). In patients with mild to
      moderately clinically active disease, FC and FL identified individuals with and
      without recurrent inflammatory disease. Faecal markers were more accurate at
      predicting clinical disease activity than C-reactive protein, platelet count or
      endoscopic appearance. CONCLUSION: FC and FL are non-invasive tests that can help
      to identify disease recurrence in symptomatic postoperative patients.

PMID- 19384913
TI  - The role of surgery in breast cancer patients with isolated bone metastases at
      the time of diagnosis.
AB  - BACKGROUND: Surgery for the primary tumor in breast cancer patients with
      synchronous isolated bone metastasis is applied for palliation. The aim was to
      determine whether surgical removal of the primary tumor provides a better
      survival and disease progression. METHODS: Forty-four patients were diagnosed
      between the dates June 2004 and January 2007 and these patients are classified
      according to the removal of the primary tumor or not. Patients and tumor
      characteristics, removal of the primary tumor, and response to systemic therapy
      are examined as the factors that were affecting overall survival and time to
      progression of the disease. RESULTS: The median follow-up time was 37.5 months.
      Mean time to progression and overall survival was longer for the patients who
      received surgery than the patients who did not (20.4 vs. 18.4 months and 57.6 vs.
      44.5 months, respectively), but these were not significant (P = 0.58, P = 0.39).
      In multivariate analysis, response to systemic treatment [(P = 0.03), hazard
      ratio = 0.44, 95% confidence interval = 0.20-0.93] was independent factor
      associated with overall survival. CONCLUSION: The response to systemic therapy is
      the major factor on survival in the breast cancer patients with isolated bone
      metastasis. Excision of the primary tumor has no effect on time to progression
      and overall survival.

PMID- 19384914
TI  - Effects of pulsed electromagnetic stimulation on patients undergoing hip revision
      prostheses: a randomized prospective double-blind study.
AB  - In this prospective, randomized, double-blind study, the effect of Pulsed
      Electromagnetic Fields (PEMFs) was investigated in 30 subjects undergoing hip
      revision using the Wagner SL stem. The subjects were treated for 6 h/day up to 90
      days after revision. Study end points were assessed clinically by the functional
      scale of Merle D'Aubigne and instrumentally by Dual-Energy X-ray Absorptiometry
      (DXA) at the Gruen zones. Subject improvement according to Merle D'Aubigne scale
      was higher (P < 0.05) in subjects undergoing active stimulation compared to
      placebo. In analyzing the DXA findings, we subtracted for each area the
      postoperative bone mineral density (BMD) values from those measured at 90 days
      and we considered all results above 3.5% as responders. There were no significant
      differences in the average BMD values at each Gruen zone between the two groups
      both postoperatively and at 90 days investigation. In Gruen zones 5 and 6,
      corresponding to the medial cortex, we observed six responders (40%) in both
      areas in the control group, while in the stimulated group we observed 14 (93%)
      and 10 (66%) responders, respectively (both P < 0.05). This study showed that
      PEMF treatment aids clinical recovery and bone stock restoration.

PMID- 19384915
TI  - Theoretical investigation on multinuclear NMR chemical shifts of some
      tris(trifluoromethyl)boron complexes.
AB  - Tris(trifluoromethyl)boron complexes have unusual properties and may find
      applications in many fields of chemistry, biology, and physics. To gain insight
      into their NMR properties, the isotropic 11B, 13C, and 19F NMR chemical shifts of
      a series of tris(trifluoromethyl)boron complexes were systematically studied
      using the gauge-included atomic orbitals (GIAO) method at the levels of B3LYP/6
      31 + G(d,p)//B3LYP/6-31G* and B3LYP/6-311 + G(d,p)//B3LYP/6-311 + G(d,p). Solvent
      effects were taken into account by polarizable continuum models (PCM). The
      calculated results were compared with the experimental values. The reason that
      the structurally inequivalent fluorine atoms in a specific species give a same
      chemical shift in experimental measurements is attributed to the fast rotation of
      CF3 group around the B-C(F3) bond because of the low energy barrier. The
      calculated 11B, 13C(F3), and 19F chemical shifts are in good agreement with the
      experimental measurements, while the deviations of calculated 13C(X, X = O, N)
      chemical shifts are slightly large. For the latter, the average absolute
      deviations of the results from B3LYP/6-311 + G(d,p)//B3LYP/6-311 + G(d,p) are
      smaller than those from B3LYP/6-31 + G(d,p)//B3LYP/6-31G*, and the inclusion of
      PCM reduces the deviation values. The calculated 19F and 11B chemical shieldings
      of (CF3)3BCO are greatly dependent on the optimized structures, while the
      influence of structural parameters on the calculated 13C chemical shieldings is
      minor.

PMID- 19384916
TI  - Improved applicability of DOSY experiments by high resolution probes combined
      with gradient amplifiers of diffusion units.
AB  - Short relaxation times and small diffusion coefficients often impede reliable
      diffusion experiments due to insufficient signal to noise ratios, especially in
      low temperature studies, where in the case of small diffusion coefficients in
      combination with very short T(2) times and substantial convection, double
      stimulated-echo experiments are required as last resort of convection
      compensating DOSY pulse sequences. Therefore, the combination of a strong
      gradient amplifier of a diffusion unit with Z-gradient high resolution probes is
      tested for low temperature applications to combine the advantages of high (1)H
      resolution, flexible temperature, and multinuclear applications with short
      gradient durations and diffusion delay. The experimental spectra on
      phosphoramidite ligands and phosphoramidite-copper complexes show that signal to
      noise improvements up to 176% were achieved despite longer eddy current delays
      and increased noise levels. Calculational estimations of the enhancement factors
      predict special benefits for systems with short transversal relaxation times and
      small diffusion coefficients and promise even higher enhancement factors for
      noise level optimized combinations. In addition, an easy way is presented to find
      fast and effectively relaxation optimized DOSY parameters for the convection
      compensated double-stimulated-echo pulse sequence of Jerschow and Muller.

PMID- 19384917
TI  - Changes in testosterone or temperature during the in vitro oocyte culture do not
      alter the sex ratio of bovine embryos.
AB  - High follicular testosterone levels have been associated with a skew in the sex
      ratio in favor of males following in vitro fertilization, whereas egg incubation
      temperature has been found to influence sex ratio in some reptiles. The
      incubation temperature interferes with the aromatase activity, resulting in a sex
      determination mechanism thought to be lost in mammals. In this work we aimed to
      test the effects of testosterone on sex ratio of bovine embryos produced in vitro
      and to determine whether effects of sex and temperature are effectively decoupled
      in mammals. Bovine oocytes were in vitro matured for 22 hr in TCM199, PVA, FSH
      and LH after a 22 hr meiotic arrest in TCM199, PVA and roscovitine 25 microM.
      Matured oocytes were in vitro fertilized and cultured up to Day 3, and embryos
      having three or more cells were sexed. In the first experiment, testosterone (0,
      30, 300 and 1,500 nM), present both during meiotic inhibition and subsequent in
      vitro maturation (IVM), did not affect development rates or embryonic sex ratio.
      In the second experiment, increasing incubation temperatures (38, 39 or 40
      degrees C) during meiotic inhibition and subsequent IVM, reduced embryo
      development, but did not change the sex ratio. Under our experimental conditions,
      testosterone does not promote a preferential selection of Y-chromosome bearing
      spermatozoa by the oocyte, and temperature and sex ratio seems to be decoupled in
      mammals.

PMID- 19384918
TI  - Pancreatic adenocarcinoma in a young patient population--12-year experience at
      Memorial Sloan Kettering Cancer Center.
AB  - BACKGROUND: There is a dearth of data in a younger population of patients with
      pancreatic ductal adenocarcinoma (PAC) regarding epidemiology, genetics,
      prognosis, and outcome. This report examines a large cohort of patients with PAC
      <or=45 years of age evaluated at MSKCC over a 12-year period. METHODS: A
      retrospective analysis of patients referred to MSKCC with PAC identified from the
      institutional tumor registry, who were <or=45 years on the date of the diagnostic
      biopsy, between January 1995 and February 2008, was performed. Information
      reviewed included demographics, clinical and pathological staging, surgical
      management, therapy, date of relapse, death or last follow-up. Survival curves
      were estimated using the Kaplan-Meier method and compared using the log-rank
      test. RESULTS: One hundred thirty-six cases of PAC, age <or=45 years at
      diagnosis, were identified. Seventy-four (54%) females, 62 (46%) males. Age
      range: 24-45; 4, 38, and 94 patients in age groups 20-29, 30-39, 40-45 years,
      respectively. Fifty (37%) had a smoking history. Fourteen (10.3%) had a positive
      family history of PAC. Thirty-five (25.7%) underwent a curative resection for
      localized disease. Twenty-eight (20.1%) presented with locally advanced,
      inoperable disease. Sixty-eight (50%) presented as AJCC Stage IV. Twenty-three
      (37%) of those resected underwent adjuvant chemoradiation. Thirteen received
      adjuvant gemcitabine. The median overall survival for the entire cohort was 12.3
      months (95% CI 10.2-14.0 months). The median overall survival for the patients
      with locally resectable disease was 41.8 months (95% CI 20.3-47 months). The
      median overall survival for the patients who presented with locally advanced,
      unresectable disease was 15.3 months (95% CI 12-19.3 months). The median overall
      survival for those who presented with metastatic disease was 7.2 months (95% CI
      5.2-9.5 months). CONCLUSIONS: This is the largest reported cohort of young
      patients with PAC <or=45 years of age. The data suggest that patients with stages
      I-II disease may have an improved prognosis, however the prognosis for stages III
      IV patients appears to be similar to the typical (older) patient population with
      PAC.

PMID- 19384919
TI  - Prenatal diagnosis of dacryocystocele.

PMID- 19384920
TI  - Dyslexia and psycho-social functioning: an exploratory study of the role of self
      esteem and understanding.
AB  - Individuals with dyslexia may have lower self-esteem and exhibit more emotional
      and behavioural difficulties than those without reading problems. However, the
      nature of any relationship between self-esteem and psychopathology remains
      unknown. This exploratory study assessed levels of self-esteem using the Self
      Perception Profile for Children (Manual for the Self-Perception Profile for
      Children. University of Denver, CO: Denver; 1985) and psycho-social adjustment
      using the Strengths and Difficulties Questionnaire (J. Child Psychol. Psychiatry,
      1997; 38: 581-586) and examined child and parent understanding, attitudes and the
      perceived impact of reading difficulties on daily life. Sixty-eight children
      assessed as dyslexic on the basis of discrepancy scores (mean age 11.2 years; 44
      male), and their parents, participated. No global self-esteem deficit was found,
      but the mean score for both child and parent-rated scholastic competence was
      significantly lower than that of the general population. Rates of social,
      emotional and behavioural difficulties were significantly higher than in the
      general population and were correlated with self-esteem. For children who had
      high global self-worth, both children and their parents had more positive
      attitudes towards their reading difficulties and were less likely to perceive a
      negative impact on relationships. The association between academic self-esteem
      and emotional symptoms is consistent with the proposed link between dyslexia and
      internalizing difficulties. Good self-esteem and a good understanding of dyslexia
      may help children avoid some of these difficulties. Further research with larger
      more representative samples is necessary as understanding the factors that
      promote successful psycho-social adjustment is essential to the development of
      effective prevention and intervention strategies.

PMID- 19384921
TI  - Light-induced aggregation of type I soluble tumor necrosis factor receptor.
AB  - We evaluated the effect of UV-B light at 302 nm on a model therapeutic protein,
      2.6 D type I soluble tumor necrosis factor receptor (sTNF-RI). This protein
      contains a single Trp at position 97 and seven native disulfide bonds along its
      interior from the N to the C-terminus. At a protein concentration of 0.1 mg/mL
      photoirradiation was found to induce the formation of soluble disulfide cross
      linked dimers with greater levels of these species formed at pH 8 than at pH 5.
      Intermolecular disulfide formation was also directly correlated with the
      photoinduced unfolding of the protein as measured by changes in secondary
      structure by CD spectroscopy. Trp was implicated as the initiator of the observed
      photoreactions by the detection of the Trp oxidation products and the absence of
      dimer formation when Trp97 was replaced with Gln. Reactive oxygen species or
      triplet state species of Trp were not involved in the reaction suggesting that
      disulfides were cleaved through one-electron reduction by either hydrated or
      peptide bound electrons produced by the photoirradiated Trp resulting in thiyl
      radical formation with disruption of the protein structure and intermolecular
      cross-linking. Photodegradation was not prevented by deoxygenation, methionine or
      sucrose commonly used for formulation of biopharmaceuticals. To our knowledge
      this is the first report directly documenting disulfide mediated aggregation
      through thiyl radical formation initiated by photoirradiation of Trp.

PMID- 19384922
TI  - ABCB1 is predominantly expressed in human fetal neural stem/progenitor cells at
      an early development stage.
AB  - ABCB1 is a human ABC transporter originally characterized by its ability to cause
      resistance to chemotherapy drugs in cancer cells, and later found to be
      functionally expressed in human neural stem/progenitor cells (NSPCs) in vitro.
      Here, we performed a detailed examination of ABCB1's expression on human NSPCs in
      vitro and in human fetal brain tissues, and analyzed the cellular properties of
      the human NSPCs expressing ABCB1. We confirmed that ABCB1 was expressed on the
      surface of human NSPCs, and its level correlated well with those of Nestin and
      CD133. The population of fluorescence-activated cell sorter-sorted human NSPCs
      expressing high levels of ABCB1 showed enrichment of proliferating cells, higher
      expression of 246 genes (e.g., RGS6, IGFBP7, GFAP, TNC, Hes1), and lower
      expression of 71 genes (e.g., STMN2, DLX5, BASP1, DCX, CD24) compared with human
      NSPCs expressing low or no ABCB1. In situ, ABCB1 was selectively expressed in
      cells in the ventricular or subventricular regions of lateral ventricles that
      expressed Nestin in human development. These findings suggest that ABCB1 is
      predominantly expressed in immature human fetal NSPCs in vitro and at early
      developmental stages in vivo, and that it may be a useful marker for human NSPCs.

PMID- 19384923
TI  - Rapid conversion of API hydrates to anhydrous forms in aqueous media.
AB  - Three anhydrous polymorphs, a monohydrate and a dihydrate of an active
      pharmaceutical ingredient, N-{[(5S)-3-(4-{6-[(1R,5S)-6-cyano-3
      oxabicyclo[3.1.0]hex-6-yl]pyridin-3-yl}phenyl)-2-oxo-1,3-oxazolidin-5
      yl]methyl}acetamide (Compound 1), have been crystallized and characterized.
      Slurry experiments and thermal data have been used to determine their relative
      thermodynamic stability. The hydrates of Compound 1 were found to be less stable
      than the most stable anhydrous Form I and converted into Form I in water within
      15 min. The rate of conversion in a dry state was found to depend on the relative
      humidity (RH) and was highest at the two RH extremes examined, 5% and 97.5% RH.

PMID- 19384925
TI  - Thermal analysis of frozen solutions: multiple glass transitions in amorphous
      systems.
AB  - Frozen aqueous solutions of sucrose exhibit two "glass transition-like" thermal
      events below the melting endotherm of ice when examined by DSC, but the physical
      basis of these events has been a source of some disagreement. In this study, a
      series of sugars, including sucrose, lactose, trehalose, maltose, fructose,
      galactose, fucose, mannose, and glucose were studied by modulated DSC and freeze
      dry microscopy in order to better understand whether sucrose is unique in any way
      with respect to this behavior, as well as to explore the physical basis, and the
      pharmaceutical significance of these multiple transitions. Double transitions
      were found to be a common feature of all sugars examined. The results are
      consistent with both thermal events being glass transitions in that (1) both
      events have second-order characteristics that appear in the reversing signals,
      (2) annealing experiments reveal that enthalpy recovery is associated with each
      transition, and (3) Lissajous plots indicate that no detectable latent heat of
      melting is associated with either transition. The data in this study are
      consistent with the idea that the lower temperature transition arises from a
      metastable glassy mixture containing more water than that in the maximally freeze
      concentrated solute. Freeze-dry microscopy observations show that for all of the
      sugars examined, it is the higher temperature transition that is associated with
      structural collapse during freeze-drying. There is no apparent pharmaceutical
      significance associated with the lower-temperature transition.

PMID- 19384924
TI  - Targeted therapy of renal cell carcinoma: synergistic activity of cG250-TNF and
      IFNg.
AB  - Immunotherapeutic targeting of G250/Carbonic anhydrase IX (CA-IX) represents a
      promising strategy for treatment of renal cell carcinoma (RCC). The well
      characterized human-mouse chimeric G250 (cG250) antibody has been shown in human
      studies to specifically enrich in CA-IX positive tumors and was chosen as a
      carrier for site specific delivery of TNF in form of our IgG-TNF-fusion protein
      (cG250-TNF) to RCC xenografts. Genetically engineered TNF constructs were
      designed as CH2/CH3 truncated cG250-TNF fusion proteins and eucariotic expression
      was optimized under serum-free conditions. In-vitro characterization of cG250-TNF
      comprised biochemical analysis and bioactivity assays, alone and in combination
      with Interferon-gamma (IFNgamma). Biodistribution data on radiolabeled [(125)J]
      cG250-TNF and antitumor activity of cG250-TNF, alone and in combination with
      IFNgamma, were measured on RCC xenografts in BALB/c nu/nu mice. Combined
      administration of cG250-TNF and IFNgamma caused synergistic biological effects
      that represent key mechanisms displaying antitumor responses. Biodistribution
      studies demonstrated specific accumulation and retention of cG250-TNF at CA-IX
      positive RCC resulting in growth inhibition of RCC and improved progression free
      survival and overall survival. Antitumor activity induced by targeted TNF-based
      constructs could be enhanced by coadministration of low doses of nontargeted
      IFNgamma without significant increase in side effects. Administration of cG250
      TNF and IFNgamma resulted in significant synergistic tumoricidal activity.
      Considering the poor outcome of renal cancer patients with advanced disease,
      cG250-TNF-based immunotherapeutic approaches warrant clinical evaluation.

PMID- 19384928
TI  - Membrane technology for purification of therapeutic proteins.
AB  - Membrane systems are used throughout the downstream purification in the
      commercial production of high value therapeutic proteins. Over the last two
      decades, new membranes, modules, and systems have been developed specifically to
      meet the requirements of the biotechnology industry. These developments have been
      facilitated by an improved fundamental understanding of: (1) the effects of
      electrostatic interactions and concentration polarization on protein transmission
      during ultrafiltration and (2) the role of membrane morphology on protein fouling
      during both sterile and virus filtration. This perspective highlights some of the
      key work in this area and provides insights into possible future improvements in
      membrane technology for the purification of recombinant therapeutic proteins.

PMID- 19384931
TI  - Poor hematopoietic stem cell mobilizers: a single institution study of incidence
      and risk factors in patients with recurrent or relapsed lymphoma.
AB  - The purpose of this retrospective study was to determine the incidence and
      predictive factors if any, of mobilization failure in lymphoma patients referred
      for autologous stem cell transplantation. A total of 588 lymphoma patients were
      referred for transplant consultation from January 2003 to December 2004.
      Predictors of mobilization failure were evaluated using logistic regression
      analysis including diagnosis, mobilization regimen, age, sex, type and number of
      prior chemotherapies, bone marrow cellularity, platelet count, white count, prior
      bone marrow involvement with malignancy, and prior radiation therapy. Two hundred
      and six patients were eligible for transplantation and underwent stem cell
      mobilization. Twenty-nine (14%) patients failed to mobilize adequate stem cells
      after the first attempt. For the entire group age (>or=60 versus <60 years),
      diagnosis (Hodgkin's versus non-Hodgkin's lymphoma), use of cytokines alone,
      platelet count <150 x 10(9)/L, and bone marrow cellularity <30% were significant
      predictors for mobilization failure on univariate analysis. In view of small
      number of patients multivariate analysis was not possible. However, a low
      platelet count (150 x 10(9)/L) was the only significant predictor when the
      analysis was restricted to non-Hodgkin's lymphoma patients who were mobilized
      with chemotherapy. Mobilization failure rates are higher in patients with non
      Hodgkin's lymphoma compared with those with Hodgkin's lymphoma. In the subset of
      patients who undergo chemomobilization for non-Hodgkin's lymphoma platelet count
      at the time of mobilization is a predictor of mobilization failure.

PMID- 19384932
TI  - Near total effacement of bone marrow by medulloblastoma.

PMID- 19384933
TI  - Laboratory identification of lupus anticoagulants.
AB  - Lupus anticoagulants (LA) are acquired autoantibodies that can cause
      antiphospholipid syndrome. LAs prolong phospholipid-dependent coagulation tests,
      acting as nonspecific inhibitors that are neutralized in the presence of excess
      phospholipid. However, there is no gold standard test and the testing is
      influenced by a number of variables. This article summarizes laboratory testing
      for LAs, with particular focus on technical issues and limitations of testing.
      Am. J. Hematol. 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19384934
TI  - Shoulder morbidity after pectoralis major flap reconstruction for head and neck
      cancer.
AB  - BACKGROUND: The effect of pectoralis major flap (PMF) harvest on shoulder
      function, allowing for the effects of neck dissection, has not previously been
      objectively measured. METHODS: Twenty-two patients who underwent PMF
      reconstruction were studied. The control group comprised 35 patients with neck
      dissection (without PMF). Neck dissections in both groups were classified into 3
      grades; grade 1: no neck dissection/selective neck dissection; grade 2: modified
      radical neck dissection; grade 3: radical neck dissection/extended radical neck
      dissection. Objective shoulder assessments were carried out using Constant score.
      RESULTS: Constant score deteriorated with grade of neck dissection (p < .005).
      The median Constant score for PMF group and neck dissection only group were 82
      and 90, respectively (p = .40). Subgroup analysis within neck dissection grade
      did not show any significant difference, but the effect of PMF was noted to be
      greatest in grade 2 patients (p = .064). CONCLUSIONS: There is minimal or low
      shoulder morbidity, additional to neck dissection, caused by PMF reconstruction
      in head and neck surgery.

PMID- 19384935
TI  - No reduction in complication rate by stay in the intensive care unit for patients
      undergoing surgery for head and neck cancer and microvascular reconstruction.
AB  - BACKGROUND: The aim of this prospective cohort study was to determine whether an
      immediate postoperative period of deep sedation and artificial respiration in an
      intensive care unit (ICU) leads to fewer complications and a reduced failure rate
      of microvascular flaps compared with a situation in which patients are allowed to
      breathe spontaneously without sedation in a recovery room. METHODS: Each group
      comprised 50 patients. General medical complications and flap donor and recipient
      site complications were documented. RESULTS: Significantly, more patients had
      problems with weaning from ventilation in the ICU group (p = .022). More cases of
      respiratory insufficiency (p = .240) and pneumonia (p = .081) occurred in the ICU
      group compared with the recovery room group without statistically significant
      differences. The number of flaps lost was comparable in both groups (p = .646).
      CONCLUSIONS: Admission to an ICU did not reduce complications after microvascular
      reconstruction and, therefore, has only to be considered for selected cases.

PMID- 19384936
TI  - MRI findings in aplastic anemia.

PMID- 19384937
TI  - Ikaros family transcription factors in chronic and acute leukemia.

PMID- 19384938
TI  - Role and prognostic significance of the Ki-67 index in non-Hodgkin's lymphoma.
AB  - Expression of Ki-67, a nuclear antigen protein present in all cycling cells, is
      used to determine the growth fraction of tumors. The aim of this study was to
      evaluate the role and prognostic significance of the Ki-67 proliferation index
      (PI) in non-Hodgkin's lymphoma. Ki-67 was assayed immunohistochemically in tissue
      samples of 319 patients with newly-diagnosed non-Hodgkin's lymphoma. In 268
      patients, the Ki-67 PI was correlated with clinical course and outcome. The mean
      Ki-67 PI ranged from 26.6% in indolent lymphomas to 97.6% in very aggressive
      lymphomas (P < 0.001). The index was <45% in 82.8% of indolent lymphomas and >45%
      in 85% of aggressive lymphomas (AUC = 0.877, P < 0.001). In patients with diffuse
      large B-cell lymphoma (n = 141), a Ki-67 PI of 70% was found to significantly
      discriminate patients with good or bad prognosis (AUC = 0.65, P = 0.004). Three
      year survival was 75% +/- 5.6% in patients with a low Ki-67 index compared with
      55.9% +/- 6% in patients with a high index (P = 0.015). In patients with a low
      IPI (<or=2), 3-year survival was 94% +/- 4% in those with a Ki-67 index <or=70%
      and 64% +/- 8.1% in those with a higher index (P = 0.002); in patients with bulky
      disease (>10 cm), the corresponding 3-year survival by Ki-67 index was 100% and
      25% +/- 12% (P = 0.012). Our results suggest that the mean Ki-67 PI differs by
      type of lymphoma. A cut-off value of 45% can help differentiate indolent from
      aggressive disease. In diffuse large B-cell lymphoma, a cut-off value of 70% can
      distinguish patients with a good and bad prognosis when combined with other
      prognostic factors of low IPI score and bulky disease.

PMID- 19384939
TI  - Microarray analysis of liver gene expression in iron overloaded patients with
      sickle cell anemia and beta-thalassemia.
AB  - Chronic transfusion therapy is used clinically to supply healthy erythrocytes for
      patients with sickle cell anemia (SCA) or beta-thalassemia major (TM). Despite
      the benefits of red blood cell transfusions, chronic transfusions lead to iron
      accumulation in key tissues such as the heart, liver, and endocrine glands.
      Transfusion-acquired iron overload is recognized as a cause of morbidity and
      mortality among patients receiving chronic transfusions. At present, there is
      little understanding of molecular events that occur during transfusional iron
      loading and the reasons for the large inter-individual variation observed
      clinically in transfusion-acquired iron accumulation. To address these issues, we
      examined whether any liver-expressed genes in SCA or TM patients with
      transfusional iron overload were associated with the degree of iron accumulation.
      Specifically, we performed microarray analysis on liver biopsy specimens
      comparing SCA patients with mild or severe iron overload and also compared SCA
      with TM patients. Fifteen candidate genes were identified with significantly
      differential expression between the high and low liver iron concentrations. SCA
      patients and 20 candidate genes were detected between the SCA and TM patient
      comparison. Subsequent quantitative PCR experiments validated 12 candidate genes;
      with GSTM1, eIF5a, SULF2, NTS, and HO-1 being particularly good prospects as
      genes that might affect the degree of iron accumulation. Future work will
      determine the baseline expression of these genes prior to transfusional iron
      overload and elucidate the full impact of these genes on the inter-individual
      variation observed clinically in transfusion-acquired iron accumulation.

PMID- 19384940
TI  - Russell bodies.

PMID- 19384941
TI  - Russell bodies and Mott cells.

PMID- 19384942
TI  - Dutcher bodies.

PMID- 19384943
TI  - WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its
      prognostic factor.
AB  - There are urgent needs to develop methods for early detection of nonsmall cell
      lung cancer (NSCLC) because of its increasing incidence and poor prognosis. Here,
      we analyzed the production of IgG antibody (WT1 Ab) against WT1 (Wilms' tumor
      gene) protein that was overexpressed in the majority of NSCLC. Enzyme-linked
      immuno-sorbent assay showed that WT1 Ab was produced in all of 91 NSCLC patients
      and 70 healthy individuals and that WT1 Ab titers were significantly higher in
      NSCLC patients compared with healthy individuals. When the cut-off level of WT1
      Ab titers were fixed at mean + 3SD of those in healthy individuals, 26.4% of
      NSCLC patients had WT1 Ab titers over the cut-off level, and positive rates of
      WT1 Ab at each clinical stage were 25.0, 30.8 and 38.4% in stage I, II and III
      NSCLC, respectively. When WT1 Ab was combined with CEA or CYFRA for detection of
      NSCLC, positive detection rates increased from 25.0 to 34.1 and 31.8%,
      respectively, in stage I and from 38.4 to 69.2 and 46.1%, respectively, in stage
      III, but not changed in stage II. Western blot analysis showed that dominant
      subclass of WT1 Ab was Th1-type IgG2. Interestingly, elevation of WT1 Ab titers
      was significantly associated with longer disease-free survival in patients with
      stages I-III NSCLC. These results showed that WT1 Ab could be a useful marker for
      early detection of NSCLC and its prognostic prediction. These results also
      suggested that WT1-specific immune responses played an important role in anti
      cancer immunity in NSCLC.

PMID- 19384945
TI  - Mass screening for colorectal cancer is not justified in most developing
      countries.
AB  - Most developed countries insist on the prevention of colorectal cancer (CRC) and
      offer screening to the population. Mass screening is proposed to both sexes in
      the population aged 50 years or more. Colonoscopy is then offered to persons
      having a positive faecal occult blood test. This recommendation should not be
      diffused over the world without considering the distinct dimensions of the risk
      and resources in developed and developing countries. A national screening policy
      is legitimate in developed countries like Japan, South Korea, and in North
      America and Europe. On the other hand, a mass screening policy for CRC is not
      recommended in most developing countries. The limited amount of resources
      attributed to health care for cancer should concern other indications in the
      control of common cancers, particularly in the cervix or liver. Indeed the risk
      of CRC is very low in most regions of Africa, and in some countries of South
      America and Asia.

PMID- 19384944
TI  - Double stranded-RNA-mediated activation of P21 gene induced apoptosis and cell
      cycle arrest in renal cell carcinoma.
AB  - Small double stranded RNAs (dsRNA) are a new class of molecules which regulate
      gene expression. Accumulating data suggest that some dsRNA can function as tumor
      suppressors. Here, we report further evidence on the potential of dsRNA mediated
      p21 induction. Using the human renal cell carcinoma cell line A498, we found that
      dsRNA targeting the p21 promoter significantly induced the expression of p21 mRNA
      and protein levels. As a result, dsP21 transfected cells had a significant
      decrease in cell viability with a concomitant G1 arrest. We also observed a
      significant increase in apoptosis. These findings were associated with a
      significant decrease in survivin mRNA and protein levels. This is the first
      report that demonstrates dsRNA mediated gene activation in renal cell carcinoma
      and suggests that forced over-expression of p21 may lead to an increase in
      apoptosis through a survivin dependent mechanism.

PMID- 19384946
TI  - Methylation of multiple genes as molecular markers for diagnosis of a small, well
      differentiated hepatocellular carcinoma.
AB  - The current study was conducted to identify robust methylation markers and their
      combinations that may prove useful for the diagnosis of early hepatocellular
      carcinoma (HCC). To achieve this, we performed in silico CpG mapping, direct
      sequencing and pyrosequencing after bisulfite treatment, and quantitative
      methylation-specific PCR (MSP) in HCC and non-HCC liver tissues. In the filtering
      group (25 HCCs), our direct sequencing analysis showed that, among the 12
      methylation genes listed by in silico CpG mapping, 7 genes (RASSF1A, CCND2,
      SPINT2, RUNX3, GSTP1, APC and CFTR) were aberrantly methylated in stages I and II
      HCCs. In the validation group (20 pairs of HCCs and the corresponding non-tumor
      liver tissues), pyrosequencing analysis confirmed that the 7 genes were
      aberrantly and strongly methylated in early HCCs, but not in any of the
      corresponding non- tumor liver tissues (p < 0.00001). The results obtained using
      our novel quantitative MSP assay correlated well with those observed using the
      pyrosequencing analysis. Notably, in MSP assay, RASSF1A showed the most robust
      performance for the discrimination of HCC and non-HCC liver tissues. Furthermore,
      a combination of RASSF1A, CCND2 and SPINT2 showed 89-95% sensitivity, 91-100%
      specificity and 89-97% accuracy in discriminating between HCC and non-HCC
      tissues, and correctly diagnosed all early HCCs. These results indicate that the
      combination of these 3 genes may aid in the accurate diagnosis of early HCC.

PMID- 19384947
TI  - A novel anticancer effect of Astragalus saponins: Transcriptional activation of
      NSAID-activated gene.
AB  - Astragalus membranaceus has been used to ameliorate the side effects of
      antineoplastic drugs because of its immunomodulating nature. We had recently
      demonstrated that total Astragalus saponins (AST) possess anticarcinogenic and
      proapoptotic properties in human colon cancer cells and tumor xenograft. In this
      study, we identified NSAID-activated gene (NAG-1) as a potential molecular target
      of AST. The growth-inhibitory and proapoptotic effects of AST were assessed in a
      panel of human cancer cell lines. Hoechst 33342 nuclear staining, Annexin V
      FITC/propidium iodide staining, Western immunoblotting, real-time PCR, luciferase
      reporter assay and electrophoretic mobility shift assay were conducted to
      determine the association of NAG-1 and related transcription factors with AST
      during its regulation of apoptotic activities. Moreover, the combined
      proapoptotic and NAG-1 promoting activities of AST and/or inhibitors of the PI3K
      Akt pathway were also examined. AST caused overexpression of NAG-1, leading to
      PARP cleavage and apoptosis. The induction of NAG-1 promoter activity by the drug
      was associated with increased gene expression, in addition to prior increase in
      Egr-1 expression and DNA binding activity. AST-induced NAG-1 activation was
      intensified when PI3K inhibitor LY294002 or Akt inhibitor was co-treated and
      reversed by NAG-1 siRNA transfection. Nevertheless, the extent of NAG-1 induction
      could not be altered by the ERK inhibitor PD98059. Our results indicate that NAG
      1 is a potential molecular target of AST in its antitumorigenic and proapoptotic
      actions, which would have additive effects when used along with PI3K-Akt
      inhibitors. The information obtained could facilitate future development of a
      novel target-specific chemotherapeutic agent with known molecular pathway.

PMID- 19384948
TI  - Merkel cell polyomavirus sequences are frequently detected in nonmelanoma skin
      cancer of immunosuppressed patients.
AB  - Recently, a new human polyoma virus has been identified in Merkel cell carcinomas
      (MCC). MCC is a highly aggressive neuroendocrine nonmelanoma skin cancer (NMSC)
      associated with immunosuppression. Clonal integration of this virus which was
      termed Merkel cell polyoma virus (MCPyV) was reported in a number of MCC.
      Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are also NMSC and
      are the most frequent cancers in the setting of immunosuppression. A unique group
      of 56 NMSC from 11 immunosuppressed patients and 147 NMSC of 125 immunocompetent
      patients was tested for MCPyV by DNA PCR, targeting the Large T Antigen and the
      structural Viral Protein 1. NMSC included SCC, BCC and Bowen's disease (BD). In
      addition, normal skin and 89 colorectal cancers were tested. MCPyV specific
      sequences were significantly more frequently found in NMSC of immunosuppressed
      patients compared to immunocompetent patients (p < 0.001). In particular BD and
      BCC revealed a significant increased association of MCPyV of immunosuppressed
      patients (p = 0.002 and p = 0.006). Forty-seven of 147 (32%) sporadic NMSC were
      MCPyV positive. Interestingly, 37.5% (36/96) of sporadic BCC of immunocompetent
      patients were MCPyV positive. No MCPyV was detected within normal skin and only 3
      out of 89 of additionally tested colorectal cancers were MCPyV positive. Our data
      show that MCPyV is a frequently reactivated virus in immunocompromized patients.
      How MCPyV contributes to the pathogenesis of NMSC, i.e., BD, SCC and BCC, in
      immunosuppressed patients and in addition, potentially to the pathogenesis of a
      subset of sporadic BCC needs further investigations.

PMID- 19384949
TI  - Histone deacetylase inhibitors suppress thymidylate synthase gene expression and
      synergize with the fluoropyrimidines in colon cancer cells.
AB  - Despite recent therapeutic advances, the response rates to chemotherapy for
      patients with metastatic colon cancer remain at approximately 50% with the
      fluoropyrimidine, 5-fluorouracil (5-FU), continuing to serve as the foundation
      chemotherapeutic agent for the treatment of this disease. Previous studies have
      demonstrated that overexpression of thymidylate synthase (TS) is a key
      determinant of resistance to 5-FU-based chemotherapy. Therefore, there is a
      significant need to develop alternative therapeutic strategies to overcome TS
      mediated resistance. In this study, we demonstrate that the histone deacetylase
      inhibitors (HDACi) vorinostat and LBH589 significantly downregulate TS gene
      expression in a panel of colon cancer cell lines. Downregulation of TS was
      independent of p53, p21 and HDAC2 expression and was achievable in vivo as
      demonstrated by mouse xenograft models. We provide evidence that HDACi treatment
      leads to a potent transcriptional repression of the TS gene. Combination of the
      fluoropyrimidines 5-FU or FUdR with both vorinostat and LBH589 enhanced cell
      cycle arrest and growth inhibition. Importantly, the downstream effects of TS
      inhibition were significantly enhanced by this combination including the
      inhibition of acute TS induction and the enhanced accumulation of the cytotoxic
      nucleotide intermediate dUTP. These data demonstrate that HDACi repress TS
      expression at the level of transcription and provides the first evidence
      suggesting a direct mechanistic link between TS downregulation and the
      synergistic interaction observed between HDACi and 5-FU. This study provides
      rationale for the continued clinical evaluation of HDACi in combination with 5-FU
      based therapies as a strategy to overcome TS-mediated resistance.

PMID- 19384950
TI  - Diosgenin targets Akt-mediated prosurvival signaling in human breast cancer
      cells.
AB  - In recent years, Akt signaling has gained recognition for its functional role in
      more aggressive, therapy-resistant malignancies. As it is frequently
      constitutively active in cancer cells, several drugs are being investigated for
      their ability to inhibit Akt signaling. The purpose of this study is to determine
      effect of diosgenin (fenugreek), a dietary compound on Akt signaling and its
      downstream targets on estrogen receptor positive (ER(+)) and estrogen receptor
      negative (ER(-)) breast cancer (BCa) cells. Diosgenin inhibits pAkt expression
      and Akt kinase activity without affecting PI3 kinase levels, resulting in the
      inhibition of its downstream targets, NF-kappaB, Bcl-2, survivin and XIAP. The
      Raf/MEK/ERK pathway, another functional downstream target of Akt, was inhibited
      by diosgenin in ER(+) but not in ER(-) BCa cells. Additionally, we found that
      diosgenin caused G1 cell cycle arrest by downregulating cyclin D1, cdk-2 and cdk
      4 expression in both ER(+) and ER(-) BCa cells resulting in the inhibition of
      cell proliferation and induction of apoptosis. Interestingly, no significant
      toxicity was seen in the normal breast epithelial cells (MCF-10A) following
      treatment with diosgenin. Additionally, in vivo tumor studies indicate diosgenin
      significantly inhibits tumor growth in both MCF-7 and MDA-231 xenografts in nude
      mice. Thus, these results suggest that diosgenin might prove to be a potential
      chemotherapeutic agent for the treatment of BCa.

PMID- 19384951
TI  - An orthotopic endometrial cancer mouse model demonstrates a role for RUNX1 in
      distant metastasis.
AB  - Endometrial carcinoma is the most common malignancy of the female genital tract
      in industrialized countries. Metastasis is the major cause of endometrial cancer
      deaths. Therefore, there is a vital need for clinically relevant in vivo models
      allowing the elucidation of the molecular and cellular mechanisms underlying
      metastatic behavior. In this study, we describe an innovative experimental
      orthotopic model of human endometrial carcinoma. Implantation in the bifurcation
      of the uterine horns resulted in tumors integrated into the myometrial
      compartment, which can be used and further exploited for the study of in vivo
      angiogenesis, myometrial invasion, and the metastatic capacity of endometrial
      cancer cells. This orthotopic model also represents a suitable tool to analyze
      how tumorigenesis and distant metastasis of endometrial cancer might be
      influenced by gene alteration, by modulating its expression in the original
      cancer cell line. One of the candidate genes implicated in endometrial cancer is
      the transcription factor RUNX1. The over-expression of RUNX1 in the endometrial
      cancer cell line HEC1A and the transplantation of these cells to the uterus of
      nude mice were associated specifically with distant metastasis in the lung. RUNX1
      plays a role in the establishment of metastases in endometrial cancer. Translated
      to the clinics, these models would be equivalent to an advanced undifferentiated
      carcinoma with node affectation (stage IIIC) and distant metastasis (stage IVB).
      These patients would be candidates for adjuvant therapy, not efficient until
      today, and therefore, our models are actually suitable for the design and
      evaluation of experimental therapies.

PMID- 19384952
TI  - Ribosome-inactivating proteins isolated from dietary bitter melon induce
      apoptosis and inhibit histone deacetylase-1 selectively in premalignant and
      malignant prostate cancer cells.
AB  - Epidemiologic evidence suggests that a diet rich in fruits and vegetables is
      associated with a reduced risk of prostate cancer (PCa) development. Although
      several dietary compounds have been tested in preclinical PCa prevention models,
      no agents have been identified that either prevent the progression of
      premalignant lesions or treat advanced disease. Momordica charantia, known as
      bitter melon in English, is a plant that grows in tropical areas worldwide and is
      both eaten as a vegetable and used for medicinal purposes. We have isolated a
      protein, designated as MCP30, from bitter melon seeds. The purified fraction was
      verified by SDS-PAGE and mass spectrometry to contain only 2 highly related
      single chain Type I ribosome-inactivating proteins (RIPs), alpha-momorcharin and
      beta-momorcharin. MCP30 induces apoptosis in PIN and PCa cell lines in vitro and
      suppresses PC-3 growth in vivo with no effect on normal prostate cells.
      Mechanistically, MCP30 inhibits histone deacetylase-1 (HDAC-1) activity and
      promotes histone-3 and -4 protein acetylation. Treatment with MCP30 induces PTEN
      expression in a prostatic intraepithelial neoplasia (PIN) and PCa cell lines
      resulting in inhibition of Akt phosphorylation. In addition, MCP30 inhibits Wnt
      signaling activity through reduction of nuclear accumulation of beta-catenin and
      decreased levels of c-Myc and Cyclin-D1. Our data indicate that MCP30 selectively
      induces PIN and PCa apoptosis and inhibits HDAC-1 activity. These results suggest
      that Type I RIPs derived from plants are HDAC inhibitors that can be utilized in
      the prevention and treatment of prostate cancer.

PMID- 19384954
TI  - Detection of different tumor growth kinetics in single transgenic mice with
      oncogene-induced mammary carcinomas by flat-panel volume computed tomography.
AB  - Transgenic mouse models offer an excellent opportunity for studying the molecular
      basis of cancer development and progression. Here we applied flat-panel volume
      computed tomography (fpVCT) to monitor tumor progression as well as the
      development of tumor vasculature in vivo in a transgenic mouse model for oncogene
      induced mammary carcinogenesis (WAP-T mice). WAP-T mice develop multiple mammary
      carcinomas on oncogene induction within 3 to 5 months. Following induction, 3
      dimensional fpVCT data sets were obtained by serial single scans of entire mice
      in combination with iodine containing contrast agents and served as basis for
      precise measurements of tumor volumes. Thereby, we were able to depict tumors
      within the mammary glands at a very early stage of the development. Tumors of
      small sizes (0.001 cm(3)) were detected by fpVCT before being palpable or visible
      by inspection. The capability to determine early tumor onset combined with
      longitudinal noninvasive imaging identified diverse time points of tumor onset
      for each mammary carcinoma and different tumor growth kinetics for multiple
      breast carcinomas that developed in single mice. Furthermore, blood supply to the
      breast tumors, as well as blood vessels around and within the tumors, were
      clearly visible over time by fpVCT. Three-dimensional visualization of tumor
      vessels in high resolution was enhanced by the use of a novel blood pool contrast
      agent. Here, we demonstrate by longitudinal fpVCT imaging that mammary carcinomas
      develop at different time points in each WAP-T mouse, and thereafter show
      divergent growth rates and distinct vascularization patterns.

PMID- 19384953
TI  - Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin
      cancer in Caucasians.
AB  - Human pigmentation is a polygenic quantitative trait with high heritability.
      Although a large number of single nucleotide polymorphisms (SNPs) have been
      identified in pigmentation genes, very few SNPs have been examined in relation to
      human pigmentary phenotypes and skin cancer risk. We evaluated the associations
      between 15 SNPs in 8 candidate pigmentation genes (TYR, TYRP1, OCA2, SLC24A5,
      SLC45A2, POMC, ASIP and ATRN) and both pigmentary phenotypes (hair color, skin
      color and tanning ability) and skin cancer risk in a nested case-control study of
      Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285
      squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases and 870
      common controls. We found that the TYR Arg402Gln variant was significantly
      associated with skin color (p-value = 7.7 x 10(-4)) and tanning ability (p-value
      = 7.3 x 10(-4)); the SLC45A2 Phe374Leu variant was significantly associated with
      hair color (black to blonde) (p-value = 2.4 x 10(-7)), skin color (p-value = 1.1
      x 10(-7)) and tanning ability (p-value = 2.5 x 10(-4)). These associations
      remained significant after controlling for MC1R variants. No significant
      associations were found between these polymorphisms and the risk of skin cancer.
      We observed that the TYRP1 rs1408799 and SLC45A2 1721 C>G were associated with
      melanoma risk (OR, 0.77; 95% CI, 0.60-0.98 and OR, 0.75; 95% CI, 0.60-0.95,
      respectively). The TYR Ser192Tyr was associated with SCC risk (OR, 1.23; 95% CI,
      1.00-1.50). The TYR haplotype carrying only the Arg402Gln variant allele was
      significantly associated with SCC risk (OR, 1.35; 95% CI, 1.04-1.74). The OCA2
      Arg419Gln and ASIP g.8818 A>G were associated with BCC risk (OR, 1.50; 95% CI,
      1.06-2.13 and OR, 0.73; 95% CI, 0.53-1.00, respectively). The haplotype near ASIP
      (rs4911414[T] and rs1015362[G]) was significantly associated with fair skin color
      (OR, 2.28; 95% CI, 1.46-3.57) as well as the risks of melanoma (OR, 1.68; 95% CI,
      1.18-2.39) and SCC (OR, 1.54; 95% CI, 1.08-2.19). These associations remained
      similar after adjusting for pigmentary phenotypes and MC1R variants. The
      statistical power of our study was modest and additional studies are warranted to
      confirm the associations observed in the present study. Our study provides
      evidence for the contribution of pigmentation genetic variants, in addition to
      the MC1R variants, to variation in human pigmentary phenotypes and possibly the
      development of skin cancer.

PMID- 19384955
TI  - The PTEN regulator DJ-1 is associated with hTERT expression in clear cell renal
      cell carcinoma.
AB  - DJ-1 is as a novel regulator of the tumor suppressor PTEN with stimulatory
      effects on PI3K-AKT/PKB signaling, one possible target of which is cMyc. The
      catalytic unit of the telomerase complex, hTERT, can be activated at different
      levels, including transcriptionally by cMyc and through phosphorylation by
      AKT/PKB. The aim of the study was to analyze the putative signaling pathway
      encompassing DJ-1, cMyc and hTERT in a series of 176 renal cell carcinomas (RCC)
      and experimentally in cell lines. DJ-1 mRNA expression was significantly elevated
      in clear cell RCC (ccRCC) compared with in papillary RCC (pRCC; p = 0.005) and
      kidney cortex tissue (p < 0.001). ccRCC and pRCC demonstrated higher cMyc RNA
      levels than in kidney cortex (p < 0.001 for both) as well as increased levels of
      hTERT RNA (p < 0.001 and p = 0.011, respectively). DJ-1 was positively correlated
      to cMyc and hTERT in ccRCC (p < 0.001 and p = 0.019, respectively), but not in
      pRCC, indicating that this pathway could have a functional significance in ccRCC.
      siRNA knock down of DJ-1 induced downregulation of cMyc and hTERT mRNA associated
      with decreased expression of pAKT and cMyc protein levels. hTERT promoter
      activity was upregulated after DJ-1 transfection and this upregulation was
      inhibited after mutation of the cMyc binding sites. These experimental data
      support the functional link among DJ-1, cMyc and hTERT expression as indicated in
      the tumor material. Neither DJ-1, cMyc nor hTERT mRNA levels were associated with
      proliferation (S-phase fraction), telomere length or prognosis in ccRCC.

PMID- 19384956
TI  - A novel role for the chemokine receptor Cxcr4 in kidney morphogenesis: an in
      vitro study.
AB  - The CXCR4 chemokine receptor is involved in hematopoietic stem cell homing,
      neuronal development, and angiogenesis. We show a significant new role for this
      receptor in epithelial patterning and renal morphogenesis. This receptor is
      expressed in the ureteric bud (UB) and the metanephric mesenchyme (MM).
      Stimulation of Cxcr4 in renal tubular cells leads to activation of multiple
      signaling pathways and tubulogenesis and cell migration. Knocking down of this
      receptor in tubular cells leads to cyst formation. Inactivation of this receptor
      in embryonic kidney explants results in impaired UB branching and mesenchymal
      tubulogenesis. The data presented here point to its importance in the process of
      mesenchymal-to-epithelial transitioning (MET), a crucial developmental process in
      the embryonic kidney. A number of genes important for normal tubulogenesis and
      MET are decreased upon CXCR4 inactivation.

PMID- 19384957
TI  - Pericellular matrix of decidua-derived mesenchymal cells: a potent human-derived
      substrate for the maintenance culture of human ES cells.
AB  - In routine culture, human embryonic stem (hES) cells are maintained on either
      feeder cells or special culture substrates such as Matrigel. However, to expand
      hES cells for clinical applications, it is desirable to minimize animal-derived
      materials in the culture for safety reasons. In this report, we show that the
      pericellular matrix prepared from human decidua-derived mesenchymal cells (PCM
      DM) is a potent substrate material that supports the growth and pluripotency of
      hES cells as efficiently as Matrigel does. This supporting activity of PCM-DM is
      stable and can be preserved for several months in the refrigerator. PCM-DM-based
      culture is compatible with non-conditioned commercial defined medium, and with
      the maintenance of dissociated hES cells in the presence of ROCK inhibitor. Since
      decidual mesenchymal cells can be prepared and expanded in a large quantity, PCM
      DM is a practical human-derived substitute for the animal-derived substrates for
      use in clinical-grade culture of hES cells.

PMID- 19384958
TI  - Fgf signaling components are associated with muscles and tendons during limb
      development.
AB  - Muscle-tendon interactions are important for the establishment of a functional
      musculoskeletal system. Fgf4 and Fgf8 are expressed in muscle and tendon boundary
      regions during limb development, suggesting a potential role for Fgf signaling
      pathway in muscle and tendon interactions. We have examined the expression of Fgf
      syn-expression group components during muscle and tendon formation of vertebrate
      limb development. We observed that the transcriptional effector of Fgf signaling,
      Pea3, and the modulators of Fgf signal, Sprouty1 and 2, were expressed in muscles
      and tendons and that their expression was enhanced at the myotendinous junctions
      in chick and mouse limbs. Analysis of Pea3 and Sprouty gene expression in
      muscleless limbs of Pax3 mutant mice indicated a major expression in muscles but
      also revealed that the Pea3 and Sprouty expression in tendons depended on
      muscles. Finally, our data showed that Fgf4 positively regulated Pea3, Sprouty1,
      and 2 expression in chick limb mesenchyme.

PMID- 19384959
TI  - Diet-induced obesity disrupts ductal development in the mammary glands of
      nonpregnant mice.
AB  - Mammary glands develop postnatally in response to the hypothalamic-pituitary
      gonadal axis. Obesity-induced changes in the local environment, however, retard
      mammary gland development during late pregnancy and lactation. To clarify the
      effects of obesity on fundamental duct development, we compared the mammary
      glands of nulliparous nonpregnant obese mice fed a high-fat diet with those of
      lean mice fed a normal diet. Obese mice had enlarged mammary glands, reflecting
      fat pad size, whereas the ducts in obese mice showed a less dense distribution
      with less frequent branching. Additionally, the ducts were surrounded by thick
      collagen layers, and were incompletely lined with myoepithelium. Because leptin
      receptors were localized in the epithelium region and leptin that was highly
      expressed in the obese glands suppressed mammary epithelial cell proliferation in
      vitro, the present results suggest that obesity disrupts mammary ductal
      development, possibly by remodeling the mammary microenvironment and promoting
      the expression of such paracrine factors as leptin.

PMID- 19384961
TI  - A microarray screen for direct targets of Zic1 identifies an aquaporin gene, aqp
      3b, expressed in the neural folds.
AB  - The Zic1 transcription factor plays multiple roles during early development, for
      example, in patterning the early neural plate and formation of the neural crest,
      somites, and cerebellum. To identify direct downstream target genes of Zic1, a
      microarray screen was conducted in Xenopus laevis that identified 85 genes
      upregulated twofold or more. These include transcription factors, receptors,
      enzymes, proteins involved in retinoic acid signaling, and an aquaglyceroporin
      (aqp-3b), but surprisingly no genes known to be involved in cell proliferation.
      We show that both aqp-3 and aqp-3b were expressed in adult tissues, while during
      early embryonic development, only aqp-3b was transcribed. During neurula stages,
      aqp-3b was expressed specifically in the neural folds. This pattern of aqp-3b
      expression closely resembled that of NF-protocadherin (NFPC), which is involved
      in cell adhesion and neural tube closure. Aqp-3b may also be involved in neural
      tube closure, since mammalian Aqp-3 promotes cell migration and proliferation.

PMID- 19384963
TI  - Patch bandits.

PMID- 19384962
TI  - Increased Hox activity mimics the teratogenic effects of excess retinoic acid
      signaling.
AB  - Excess retinoic acid (RA) signaling can be teratogenic and result in cardiac
      birth defects, but the cellular and molecular origins of these defects are not
      well understood. Excessive RA signaling can completely eliminate heart formation
      in the zebrafish embryo. However, atrial and ventricular cells are differentially
      sensitive to more modest increases in RA signaling. Increased Hox activity,
      downstream of RA signaling, causes phenotypes similar to those resulting from
      excess RA. These results suggest that Hox activity mediates the differential
      effects of ectopic RA on atrial and ventricular cardiomyocytes and may underlie
      the teratogenic effects of RA on the heart.

PMID- 19384966
TI  - Age-related macular degeneration and functional promoter and coding variants of
      the apolipoprotein E gene.
AB  - Age-related macular degeneration (AMD) is a frequent, multifactorial disease of
      the central retina and a major cause of irreversible vision loss in
      industrialized countries. Apolipoprotein E (APOE) has been consistently
      associated with AMD, particularly its two functional isoforms E2 (predisposing)
      and E4 (protective). The biological correlate of this association, however, is
      still unclear. In this study, we have defined an extended haplotype block
      encompassing the entire APOE gene locus, including known coding as well as cis
      regulatory promoter variants. Of the five extended APOE haplotypes common in the
      general population, two were found to be significantly associated with AMD,
      namely G-G-G-G-epsilon2 (odds ratio [OR], 1.59; 95% confidence interval [CI],
      1.19-2.12) and T-G-A-G-epsilon4 (OR, 0.76; 95% CI, 0.58-0.99). When analyzing
      common extended haplotype combinations, T-C-G-G-epsilon3/T-G-A-G-epsilon4
      exhibited the most prominent effect (OR, 0.32; 95% CI, 0.20-0.51). Intriguingly,
      we also found one extended epsilon3-haplotype, G-G-G-A-epsilon3, to be protective
      in the homozygous state (OR, 0.65; 95% CI, 0.49-0.87). Since single nucleotide
      polymorphism (SNP) rs405509:G>T is a constituent of the extended epsilon
      haplotype block and is known to significantly influence APOE promoter activity,
      we hypothesize that both the relative rate of APOE isoform expression in
      conjunction with established functional differences of the respective isoforms
      may be crucial in mediating AMD pathology. This would also imply that genotyping
      of the core epsilon-haplotypes alone is not sufficient to estimate AMD risk, but
      that determination of extended haplotype combinations, including the functional
      promoter SNP rs405509, is required instead.

PMID- 19384970
TI  - Genomic variation in a global village: report of the 10th annual Human Genome
      Variation Meeting 2008.
AB  - The Centre for Applied Genomics of the Hospital for Sick Children and the
      University of Toronto hosted the 10th Human Genome Variation (HGV) Meeting in
      Toronto, Canada, in October 2008, welcoming about 240 registrants from 34
      countries. During the 3 days of plenary workshops, keynote address, and poster
      sessions, a strong cross-disciplinary trend was evident, integrating expertise
      from technology and computation, through biology and medicine, to ethics and law.
      Single nucleotide polymorphisms (SNPs) as well as the larger copy number variants
      (CNVs) are recognized by ever-improving array and next-generation sequencing
      technologies, and the data are being incorporated into studies that are
      increasingly genome-wide as well as global in scope. A greater challenge is to
      convert data to information, through databases, and to use the information for
      greater understanding of human variation. In the wake of publications of the
      first individual genome sequences, an inaugural public forum provided the
      opportunity to debate whether we are ready for personalized medicine through
      direct-to-consumer testing. The HGV meetings foster collaboration, and fruits of
      the interactions from 2008 are anticipated for the 11th annual meeting in
      September 2009.

PMID- 19384968
TI  - Morphometric analysis of testis cord formation in Sox9-EGFP mice.
AB  - Sox9-EGFP knockin mice were generated to label Sertoli cells and visualize testis
      cord formation during development. Confocal microscopy and morphometric analysis
      of developing cords were performed. Serial histological sections were used for
      three-dimensional cord reconstruction. Initially, gonad length decreased from
      embryonic day (E) 11.5 to E13.5, but increased thereafter, while gonad width
      doubled every 12 hours from E11.5 through E14.5. At E12.5, the average number of
      cords was 12.5, whereas this decreased to 10.4 at E13.5 and E14.5. Cord number at
      a given time point varied between gonads and influenced dimensions. The initial
      cords that formed were complex and branches were common. Time-lapse imaging
      revealed an intricate behavior of the Sertoli-germ cell mass and cellular
      exchange between connected neighboring cords. These results suggest that cord
      formation is a highly dynamic process that subsequently becomes refined to
      establish the final number of seminiferous tubule precursors.

PMID- 19384972
TI  - Different functional consequences of two missense mutations in the GJB2 gene
      associated with non-syndromic hearing loss.
AB  - Mutations in the GJB2 gene, which encodes the gap junction (GJ) protein
      connexin26 (Cx26), are the most common cause of inherited non-syndromic hearing
      loss (NSHL). We identified two missense mutations, p.D46E (c.138T>G) and p.T86R
      (c.257C>G), of GJB2 in Korean HL families. The novel p.D46E mutation exhibited
      autosomal dominant inheritance, while the p.T86R mutation, which is exclusively
      found in Asians, segregated with an autosomal recessive pattern. Thus, we sought
      to elucidate the pathogenic nature of such different inherited patterns of HL. We
      studied protein localization and gap junction functions in cells transfected with
      wild-type or mutant Cx26 tagged with fluorescent proteins, which allowed visual
      confirmation of homozygous or heterozygous mutant GJs. The Cx26-D46E mutant was
      targeted to the plasma membrane, but this mutant protein failed to transfer
      Ca(2+) or propidium iodide intercellularly, suggesting disruption of both ionic
      and biochemical coupling. Heterozygous GJs also showed dysfunctional
      intercellular couplings and hemichannel opening, confirming the dominant-negative
      nature of the p.D46E mutation. The Cx26-T86R mutant protein did not form GJs,
      since the mutated protein was confined in the cytoplasm and not transported to
      the cell membrane. When Cx26-T86R was co-expressed with Cx26-WT, ionic and
      biochemical coupling was normal, consistent with the recessive nature of the
      mutation. These studies revealed distinct pathogenic mechanisms of two GJB2
      mutations identified in Korean families.

PMID- 19384973
TI  - Relationship between caffeine intake and plasma sex hormone concentrations in
      premenopausal and postmenopausal women.
AB  - BACKGROUND: Circulating estrogens and androgens are important factors in the
      development of various female cancers. Caffeine intake may decrease risk of
      breast and ovarian cancer, although the data are not entirely consistent. Whether
      or not caffeine affects cancer risk by altering sex hormone levels is currently
      unknown. METHODS: We examined the relationship of caffeine, coffee, decaffeinated
      coffee, and tea with plasma concentrations of estrogens, androgens, progesterone,
      prolactin, and sex hormone-binding globulin (SHBG) in 524 premenopausal and 713
      postmenopausal women from the Nurses' Health Study (NHS) and NHSII. RESULTS: In
      premenopausal women, caffeine intake was inversely associated with luteal total
      and free estradiol, and positively associated with luteal progesterone levels (P
      trend = .02, .01, .03, respectively). Coffee intake was significantly associated
      with lower luteal total and free estradiol levels, but not luteal progesterone
      levels (P-trend = .007, .004, .20, respectively). Among the postmenopausal women,
      there was a positive association between caffeine and coffee intake and SHBG
      levels (P-trend = .03 and .06, respectively). No significant associations were
      detected with the other hormones. CONCLUSIONS: Data from this cross-sectional
      study suggest that caffeine may alter circulating levels of luteal estrogens and
      SHBG, representing possible mechanisms by which coffee or caffeine may be
      associated with pre- and postmenopausal malignancies, respectively. Future
      studies evaluating how caffeine-mediated alterations in sex hormones and binding
      protein levels affect the risk of female cancers are warranted.

PMID- 19384974
TI  - Baculovirus complementation restores a novel NDUFAF2 mutation causing complex I
      deficiency.
AB  - Mitochondrial complex I deficiency is the most common defect of the OXPHOS
      system. We report a patient from consanguineous parents with a complex I
      deficiency expressed in skin fibroblasts. Homozygosity mapping revealed several
      homozygous regions with candidate genes, including the gene encoding an assembly
      factor for complex I, NDUFAF2. Screening of this gene on genomic DNA revealed a
      homozygous stop-codon resulting in a truncation of the protein at position 38.
      The mutation causes a severely reduced activity and a disturbed assembly of
      complex I. A baculovirus containing the GFP-tagged wild-type NDUFAF2 gene was
      used to prove the functional consequences of the mutation. The expression and
      activity of complex I was almost completely rescued by complementation of the
      patient fibroblasts with the baculovirus. Therefore, the homozygous substitution
      in NDUFAF2 is the disease-causing mutation, which results in a complex I
      deficiency in the fibroblasts of the patient.

PMID- 19384975
TI  - Characterization of star adhesive sealants based on PEG/dextran hydrogels.
AB  - Swellable PEG amine/dextran aldehyde composite materials are emerging as a
      controlled, biocompatible tissue adhesive. We explain how preservation of natural
      tissue amines provides biocompatibility for PEG/dextran that exceeds the
      stringent, destructive cyanide-based chemistry of cyanoacrylates, and adhere far
      better than fibrin glue. Strategic variations of material composition allow for
      the improvement of biocompatibility and adhesion strength. Material variations
      can be tailored to match the needs of specific tissue beds for an array of
      clinical applications. PEG/dextran cohesive properties are most responsive to
      variations in the PEG component (number of arms and solid content), while
      tissue/material adhesion strength is primarily determined by the number of
      aldehydes in the dextran.

PMID- 19384976
TI  - Properties and bioapplications of blended cellulose and corn protein films.
AB  - A series of blend films have been prepared from cellulose and corn protein in a
      NaOH/urea solution by a simple, low cost, and 'green' pathway. Their structure
      and properties are characterized by amino acid analysis, X-ray diffraction,
      scanning electron microscopy, thermogravimetry, and tensile testing. The results
      reveal that a certain miscibility exists between cellulose and corn protein and
      their thermal stability and mechanical properties are improved significantly,
      compared with the protein materials, when the protein content is less than 18 wt.
      %. The protein, which contains tyrosine and histidine, could remain in the blend
      films after being washed for ten days, which indicates the strong hydrogen
      bonding between the hydroxy groups of cellulose and the hydroxyphenyl of tyrosine
      and imidazolyl of histidine in the protein. Furthermore, they exhibit good
      biocompatibility capable of supporting cell adhesion and proliferation.

PMID- 19384977
TI  - Gel-like structure of a hexadecyl derivative of hyaluronic acid for the treatment
      of osteoarthritis.
AB  - Hyaluronic acid is a polysaccharide with viscoelastic and mechanical properties
      that are crucial for the normal functioning of osteoarticular junctions. It is
      demonstrated that introduction of a hexadecyl side chain into HA yields an
      injectable polysaccharide capable of forming physical hydrogels, which are stable
      at very low polymer concentrations, whereas native hyaluronic acid forms viscous
      solutions at concentrations that are ten times higher. Characterization of this
      system showed that the driving force for its gel-like behavior is the occurrence
      of hydrophobic interactions involving aliphatic side chains, despite the low
      degree of substitution, as confirmed by molecular dynamics simulations of HYADD4
      and HA hydrogels.

PMID- 19384978
TI  - Application of 1-allyl-3-(1-butyl)imidazolium chloride in the synthesis of
      cellulose esters: properties of the ionic liquid, and comparison with other
      solvents.
AB  - The ionic liquid (IL), 1-allyl-3-(1-butyl)imidazolium chloride (AlBuImCl), has
      been synthesized and its properties determined. Increase in the temperature
      increased its conductivity and decreased its density, polarity, and viscosity.
      Microcrystalline cellulose (MCC), dissolves in this IL by heating at 80 degrees
      C; this did not affect its degree of polymerization, decreased its index of
      crystallinity (Ic), and changed in morphology after regeneration. Convenient
      acylation of MCC was achieved by using 50% excess anhydride at 80 degrees C, for
      24 or 48 h for acetic and butyric anhydride, respectively. The composition of the
      mixed esters depended on the initial ratio of the anhydrides, and their order of
      addition.

PMID- 19384979
TI  - Reverse thermal organogelation of poly(ethylene glycol)-polypeptide diblock
      copolymers in chloroform.
AB  - Most organogel formation has been observed at low temperatures and the gel melts
      as the temperature increases. As an opposite case to traditional organogels, we
      report a reverse thermal gelation of methoxy-aminopoly(ethylene glycol)
      homopolypeptide block-copolymer chloroform solutions that undergo a sol-to-gel
      transition as the temperature increases. A series of methoxy-aminopoly(ethylene
      glycol)-homopolypeptide block copolymers showing reverse thermal gelation in
      chloroform was synthesized and we prove that the secondary structure of the
      polypeptide determines the morphology of the organogel.

PMID- 19384981
TI  - The immediate-early oncoproteins Fra-1, c-Fos, and c-Jun have distinguishable
      surface behavior and interactions with phospholipids.
AB  - This work explores the surface properties of the transcription factor Fra-1 and
      compares them with those of two other immediate early proteins, c-Fos and c-Jun,
      to establish generalities and differences in the surface behavior and interaction
      with phospholipids of this type of proteins. We present several experimental
      clues of the flexible nature of Fra-1, c-Fos, and c-Jun that support sequence
      based predictions of their intrinsical disorder. The values of surface parameters
      for Fra-1 are similar in general to those of c-Fos and c-Jun. However, we find
      differences in the interactions of the three proteins with phospholipids. The
      closely related Fra-1 and c-Fos share affinity for anionic lipids but the former
      has more affinity for a condensed phase and senses a change in DPPC phase, while
      the latter has more affinity for an expanded phase. These features are in
      contrast with our previous finding that c-Jun is not selective for phospholipid
      polar head group or charge. We show here that at least some immediate early
      transcription factors can interact with membrane phospholipids in a
      distinguishable manner, and this shall provide a basis for their potential
      capacity to regulate membrane-mediated cellular processes.

PMID- 19384982
TI  - Single-molecule pair studies of the interactions of the alpha-GalNAc (Tn-antigen)
      form of porcine submaxillary mucin with soybean agglutinin.
AB  - Mucins form a group of heavily O-glycosylated biologically important
      glycoproteins that are involved in a variety of biological functions, including
      modulating immune response, inflammation, and adhesion. Mucins are also involved
      in cancer and metastasis and often express diagnostic cancer antigens. Recently,
      a modified porcine submaxillary mucin (Tn-PSM) containing GalNAcalpha1-O-Ser/Thr
      residues was shown to bind to soybean agglutinin (SBA) with approximately 10(6)
      fold enhanced affinity relative to GalNAcalpha1-O-Ser, the pancarcinoma
      carbohydrate antigen. In this study, dynamic force spectroscopy is used to
      investigate molecular pairs of SBA and Tn-PSM. A number of force jumps that
      demonstrate unbinding or rebinding events were observed up to a distance equal to
      2.0 microm, consistent with the length of the mucin chain. The unbinding force
      increased from 103 to 402 pN with increasing force loading rate. The position of
      the activation barrier in the energy landscape of the interaction was 0.1 nm. The
      lifetime of the SBA-TnPSM complex in the absence of applied force was determined
      to be in the range 1.3-1.9 s. Kinetic parameters describing the rate of
      dissociation of other sugar lectin interactions are in the range 3.3 x 10(-3)-2.5
      x 10(-3) s. The long lifetime of the SBA-TnPSM complex is compatible with a
      binding model in which lectin molecules "bind and jump" from alpha-GalNAc residue
      to alpha-GalNAc residue along the polypeptide chain of Tn-PSM before
      dissociating. These findings have important implications for the molecular
      recognition properties of mucins.

PMID- 19384983
TI  - Rat mitochondrial manganese superoxide dismutase: amino acid positions involved
      in covalent modifications, activity, and heat stability.
AB  - The role of three amino acid residues (Q143, Y34, S82) of rat mitochondrial
      superoxide dismutase (ratSOD2) in the enzymatic activity, thermostability, and
      post-translational modification of the enzyme was investigated through site
      directed mutagenesis studies. Six recombinant forms of the enzyme were produced,
      carrying the Q143 or H143 residue with or without the Y34F or S82A replacement.
      All proteins bound manganese as active cofactor and were organized as
      homotetramers. The greatest effect on the activity (sixfold reduction) was
      observed in ratSOD2 forms containing the H143 variant, whereas Y34F and S82A
      substitutions moderately reduced the enzymatic activity compared to the Q143
      form. Heat inactivation studies showed the high thermo-tolerance of ratSOD2 and
      allowed an evaluation of the related activation parameters of the heat
      inactivation process. Compared to Q143, the H143 variant was significantly less
      heat stable and displayed moderately lower enthalpic and entropic factors; the
      Y34F substitution caused a moderate reduction of heat stability, whereas the S82A
      replacement slightly improved the thermo-tolerance of the Q143 variant; both
      substitutions significantly increased enthalpic and entropic factors of heat
      inactivation, the greatest effect being observed with S82A substitution. All
      recombinant forms of ratSOD2 were glutathionylated in Escherichia coli, a feature
      pointing to the high reactivity of ratSOD2 toward glutathione. Moreover, the S82
      position of the enzyme was phosphorylated in an in vitro system containing human
      mitochondrial protein extracts as source of protein kinases. These data highlight
      the role played by some residues in ratSOD2 and suggest a fine regulation of the
      enzyme occurring in vivo.

PMID- 19384984
TI  - Evaluation at atomic resolution of the role of strain in destabilizing the
      temperature-sensitive T4 lysozyme mutant Arg 96 --> His.
AB  - Mutant R96H is a classic temperature-sensitive mutant of bacteriophage T4
      lysozyme. It was in fact the first variant of the protein to be characterized
      structurally. Subsequently, it has been studied extensively by a variety of
      experimental and computational techniques, but the reasons for the loss of
      stability of the mutant protein remain controversial. In the crystallographic
      refinement of the mutant structure at 1.9 A resolution one of the bond angles at
      the site of substitution appeared to be distorted by about 11( degrees ), and it
      was suggested that this steric strain was one of the major factors in
      destabilizing the mutant. Different computationally-derived models of the mutant
      structure, however, did not show such distortion. To determine the geometry at
      the site of mutation more reliably, we have extended the resolution of the data
      and refined the wildtype (WT) and mutant structures to be better than 1.1 A
      resolution. The high-resolution refinement of the structure of R96H does not
      support the bond angle distortion seen in the 1.9 A structure determination. At
      the same time, it does confirm other manifestations of strain seen previously
      including an unusual rotameric state for His96 with distorted hydrogen bonding.
      The rotamer strain has been estimated as about 0.8 kcal/mol, which is about 25%
      of the overall reduction in stability of the mutant. Because of concern that
      contacts from a neighboring molecule in the crystal might influence the geometry
      at the site of mutation we also constructed and analyzed supplemental mutant
      structures in which this crystal contact was eliminated. High-resolution
      refinement shows that the crystal contacts have essentially no effect on the
      conformation of Arg96 in WT or on His96 in the R96H mutant.

PMID- 19384985
TI  - Development of a CE-ESI-ITMS method for the enantiomeric determination of the non
      protein amino acid ornithine.
AB  - Unequivocal enantiomeric determination by CE-MS2 of the non-protein amino acid
      ornithine (Orn), previously derivatized with FITC, was carried out in this work.
      A CE-tandem MS system was used to combine the potential of CE in chiral
      separations with the sensitivity and selectivity of tandem MS detection. The
      electrospray-coaxial sheath flow interface conditions were optimized and an IT
      analyzer working in the MS2 mode was employed to provide the best sensitivity and
      selectivity. Satisfactory results were obtained in terms of linearity (r2 >
      0.99), precision (RSD from 1.3 to 2.3% for migration times and from 11.0 to 18.6%
      for corrected peak areas), and LOD (2 x 10(-9) M). Interestingly, the CE-MS2
      method developed allowed a sensitivity enhancement of 100 folds with respect to
      UV detection. The results demonstrated the feasibility for carrying out
      quantitative CE-ESI-MS2 determinations of Orn enantiomers in beers. Thus, L-Orn
      was found in the 16 beer samples analyzed at concentrations ranging from 1 x 10(
      6) to 2 x 10(-5) M, whereas the percentages of D-Orn with respect to the total
      amount of Orn reached values between 1.5 and 10.0%.

PMID- 19384986
TI  - Analytical method for simultaneous determination of pesticide and veterinary drug
      residues in milk by CE-MS.
AB  - This study reports a method based on CE-MS/MS detection developed for the
      multiresidue determination of seven pesticides (amidosulfuron, cyprodinil,
      cyromazine, imazaquin, pirimicarb, demethyl pirimicarb, procymidone) and eight
      residues of veterinary drugs (ciprofloxacin, enrofloxacin, sulfacetamide,
      sulfabenzamide, sulfachlorpyridazine, sulfaquinoxaline, sulfathiazole,
      sulfisoxazole), whose contents are regulated by the EU Council Regulations no.
      396/2005 and no. 2377/90, in animal edible tissues. Milk samples were extracted
      with ACN and the extract was cleaned up using an Oasis hydrophilic-lipophilic
      balance SPE cartridge. The proposed method was validated in accordance with the
      European Commission Decision 657/2002. MS/MS experiments, using an IT analyzer,
      operating in multiple reaction monitoring mode, were carried out to achieve the
      minimum number of required identification points. Recovery data were also
      satisfactory, with values higher than 78% for most pesticides and veterinary
      drugs extracted from milk spiked at half the maximum residue limit established
      for the studied compounds. The RSD% (n = 5) were lower than 13 and 15% for intra
      day and inter-day assays, respectively. The method was applied to establish the
      occurrence of the studied pesticides in 100 milk samples, attaining the
      determination of pesticide and veterinary drug residues in milk in the low
      microg/kg range.

PMID- 19384987
TI  - Conformational choices for the stereochemically constrained gamma-amino acid
      residue gabapentin: theoretical studies and correlation with experimental
      results.
AB  - Gabapentin (1-aminomethylcyclohexaneacetic acid, Gpn) is an achiral,
      conformationally constrained gamma amino acid residue. A survey of available
      crystal structures of Gpn peptides reveals that the torsion angles about the
      C(gamma)-C(beta) (theta(1)) and C(beta)-C(alpha) (theta(2)) bonds are
      overwhelmingly limited to gauche, gauche (g(+)g(+)/g(-)g(-)) conformations. The
      Gpn residue forms C(7) and C(9) hydrogen bonds in which the donor and acceptor
      atoms come from the flanking peptide units. In combination with alpha amino acid
      residues alphagamma and gammaalpha segments can adopt C(12) hydrogen bonded
      structures. The conformational choices available to the Gpn residue have been
      probed using energy calculations, adopting a grid search strategy. Ramachandran
      phi-psi maps have been constructed for fixed values of theta(1) and theta(2),
      corresponding to the gauche and trans conformations. The sterically allowed and
      energetically favorable regions of conformational space have been defined and
      experimental observations compared. C(7) and C(9) hydrogen bonded conformational
      families have been identified using a grid search approach in which theta(1) and
      theta(2) values are varied over a range of +/-10 degrees about ideal values at 1
      degrees intervals. The theoretical analysis together with experimental
      observations for 59 Gpn residues from 35 crystal structures permits definition of
      the limited range of conformational possibilities at this gamma amino acid
      residue.

PMID- 19384988
TI  - Contributions of all 20 amino acids at site 96 to the stability and structure of
      T4 lysozyme.
AB  - To try to resolve the loss of stability in the temperature-sensitive mutant of T4
      lysozyme, Arg 96 --> His, all of the remaining 18 naturally occurring amino acids
      were substituted at site 96. Also, in response to suggestions that the charged
      residues Lys85 and Asp89, which are 5-8 A away, may have important effects, each
      of these amino acids was replaced with alanine. Crystal structures were
      determined for many of the variants. With the exception of the tryptophan and
      valine mutants R96W and R96V, the crystallographic analysis shows that the
      substituted side chain following the path of Arg96 in wildtype (WT). The melting
      temperatures of the variants decrease by up to approximately 16 degrees C with WT
      being most stable. There are two site 96 replacements, with lysine or glutamine,
      that leave the stability close to that of WT. The only element that the side
      chains of these residues have in common with the WT arginine is the set of three
      carbon atoms at the C(alpha), C(beta), and C(gamma) positions. Although each side
      chain is long and flexible with a polar group at the distal position, the details
      of the hydrogen bonding to the rest of the protein differ in each case. Also, the
      glutamine replacement lacks a positive charge. This shows that there is some
      adaptability in achieving full stabilization at this site. At the other extreme,
      to be maximally destabilizing a mutation at site 96 must not only eliminate
      favorable interactions but also introduce an unfavorable element such as steric
      strain or a hydrogen-bonding group that remains unsatisfied. Overall, the study
      highlights the essential need for atomic resolution site-specific structural
      information to understand and to predict the stability of mutant proteins. It can
      be very misleading to simply assume that conservative amino acid substitutions
      cause small changes in stability, whereas large stability changes are associated
      with nonconservative replacements.

PMID- 19384989
TI  - Structural and functional modularity of proteins in the de novo purine
      biosynthetic pathway.
AB  - It is generally accepted that naturally existing functional domains can serve as
      building blocks for complex protein structures, and that novel functions can
      arise from assembly of different combinations of these functional domains. To
      inform our understanding of protein evolution and explore the modular nature of
      protein structure, two model enzymes were chosen for study, purT-encoded
      glycinamide ribonucleotide formyltransferase (PurT) and purK-encoded N(5)
      carboxylaminoimidazole ribonucleotide synthetase (PurK). Both enzymes are found
      in the de novo purine biosynthetic pathway of Escherichia coli. In spite of their
      low sequence identity, PurT and PurK share significant similarity in terms of
      tertiary structure, active site organization, and reaction mechanism. Their
      characteristic three domain structures categorize both PurT and PurK as members
      of the ATP-grasp protein superfamily. In this study, we investigate the
      exchangeability of individual protein domains between these two enzymes and the
      in vivo and in vitro functional properties of the resulting hybrids. Six domain
      swapped hybrids were unable to catalyze full wild-type reactions, but each hybrid
      protein could catalyze partial reactions. Notably, an additional loop replacement
      in one of the domain-swapped hybrid proteins was able to restore near wild-type
      PurK activity. Therefore, in this model system, domain-swapped proteins retained
      the ability to catalyze partial reactions, but further modifications were
      required to efficiently couple the reaction intermediates and achieve catalysis
      of the full reaction. Implications for understanding the role of domain swapping
      in protein evolution are discussed.

PMID- 19384990
TI  - Structural origin of weakly ordered nitroxide motion in spin-labeled proteins.
AB  - A disulfide-linked nitroxide side chain (R1) used in site-directed spin labeling
      of proteins often exhibits an EPR spectrum characteristic of a weakly ordered z
      axis anisotropic motion at topographically diverse surface sites, including those
      on helices, loops and edge strands of beta-sheets. To elucidate the origin of
      this motion, the first crystal structures of R1 that display simple z-axis
      anisotropic motion at solvent-exposed helical sites (131 and 151) and a loop site
      (82) in T4 lysozyme have been determined. Structures of 131R1 and 151R1
      determined at cryogenic or ambient temperature reveal an intraresidue C(alpha)-
      H...S(delta) interaction that immobilizes the disulfide group, consistent with a
      model in which the internal motions of R1 are dominated by rotations about the
      two terminal bonds (Columbus, Kalai, Jeko, Hideg, and Hubbell, Biochemistry
      2001;40:3828-3846). Remarkably, the 131R1 side chain populates two rotamers
      equally, but the EPR spectrum reflects a single dominant dynamic population,
      showing that the two rotamers have similar internal motion determined by the
      common disulfide-backbone interaction. The anisotropic motion for loop residue
      82R1 is also accounted for by a common disulfide-backbone interaction, showing
      that the interaction does not require a specific secondary structure. If the
      above observations prove to be general, then significant variations in order and
      rate for R1 at noninteracting solvent-exposed helical and loop sites can be
      assigned to backbone motion because the internal motion is essentially constant.

PMID- 19384991
TI  - Contribution of individual histidines to the global stability of human prolactin.
AB  - A member of the family of hematopoietic cytokines human prolactin (hPRL) is a 23k
      kDa polypeptide hormone, which displays pH dependence in its structural and
      functional properties. The binding affinity of hPRL for the extracellular domain
      of its receptor decreases 500-fold over the relatively narrow, physiologic pH
      range from 8 to 6; whereas, the affinity of human growth hormone (hGH), its
      closest evolutionary cousin, does not. Similarly, the structural stability of
      hPRL decreases from 7.6 to 5.6 kcal/mol from pH 8 to 6, respectively, whereas the
      stability of hGH is slightly increased over this same pH range. hPRL contains
      nine histidines, compared with hGH's three, and they are likely responsible for
      hPRL's pH-dependent behavior. We have systematically mutated each of hPRL's
      histidines to alanine and measured the effect on pH-dependent global stability.
      Surprisingly, a vast majority of these mutations stabilize the native protein, by
      as much as 2-3 kcal/mol. Changes in the overall pH dependence to hPRL global
      stability can be rationalized according to the predominant structural
      interactions of individual histidines in the hPRL tertiary structure. Using
      double mutant cycles, we detect large interaction free energies within a cluster
      of nearby histidines, which are both stabilizing and destabilizing to the native
      state. Finally, by comparing the structural locations of hPRL's nine histidines
      with their homologous residues in hGH, we speculate on the evolutionary role of
      replacing structurally stabilizing residues with histidine to introduce pH
      dependence to cytokine function.

PMID- 19384992
TI  - Apolipoprotein AI tertiary structures determine stability and phospholipid
      binding activity of discoidal high-density lipoprotein particles of different
      sizes.
AB  - Human high-density lipoprotein (HDL) plays a key role in the reverse cholesterol
      transport pathway that delivers excess cholesterol back to the liver for
      clearance. In vivo, HDL particles vary in size, shape and biological function.
      The discoidal HDL is a 140-240 kDa, disk-shaped intermediate of mature HDL.
      During mature spherical HDL formation, discoidal HDLs play a key role in loading
      cholesterol ester onto the HDL particles by activating the enzyme,
      lecithin:cholesterol acyltransferase (LCAT). One of the major problems for high
      resolution structural studies of discoidal HDL is the difficulty in obtaining
      pure and, foremost, homogenous sample. We demonstrate here that the commonly used
      cholate dialysis method for discoidal HDL preparation usually contains 5-10%
      lipid-poor apoAI that significantly interferes with the high-resolution
      structural analysis of discoidal HDL using biophysical methods. Using an
      ultracentrifugation method, we quickly removed lipid-poor apoAI. We also purified
      discoidal reconstituted HDL (rHDL) into two pure discoidal HDL species of
      different sizes that are amendable for high-resolution structural studies. A
      small rHDL has a diameter of 7.6 nm, and a large rHDL has a diameter of 9.8 nm.
      We show that these two different sizes of discoidal HDL particles display
      different stability and phospholipid-binding activity. Interestingly, these
      property/functional differences are independent from the apoAI alpha-helical
      secondary structure, but are determined by the tertiary structural difference of
      apoAI on different discoidal rHDL particles, as evidenced by two-dimensional NMR
      and negative stain electron microscopy data. Our result further provides the
      first high-resolution NMR data, demonstrating a promise of structural
      determination of discoidal HDL at atomic resolution using a combination of NMR
      and other biophysical techniques.

PMID- 19384993
TI  - Practical protocols for production of very high yields of recombinant proteins
      using Escherichia coli.
AB  - The gram-negative bacterium Escherichia coli offers a mean for rapid, high yield,
      and economical production of recombinant proteins. However, high-level production
      of functional eukaryotic proteins in E. coli may not be a routine matter,
      sometimes it is quite challenging. Techniques to optimize heterologous protein
      overproduction in E. coli have been explored for host strain selection, plasmid
      copy numbers, promoter selection, mRNA stability, and codon usage, significantly
      enhancing the yields of the foreign eukaryotic proteins. We have been working on
      optimizations of bacterial expression conditions and media with a focus on
      achieving very high cell density for high-level production of eukaryotic
      proteins. Two high-cell-density bacterial expression methods have been explored,
      including an autoinduction introduced by Studier (Protein Expr Purif 2005;41:207
      234) recently and a high-cell-density IPTG-induction method described in this
      study, to achieve a cell-density OD(600) of 10-20 in the normal laboratory
      setting using a regular incubator shaker. Several practical protocols have been
      implemented with these high-cell-density expression methods to ensure a very high
      yield of recombinant protein production. With our methods and protocols, we
      routinely obtain 14-25 mg of NMR triple-labeled proteins and 17-34 mg of
      unlabeled proteins from a 50-mL cell culture for all seven proteins we tested.
      Such a high protein yield used the same DNA constructs, bacterial strains, and a
      regular incubator shaker and no fermentor is necessary. More importantly, these
      methods allow us to consistently obtain such a high yield of recombinant proteins
      using E. coli expression.

PMID- 19384994
TI  - Systematic structural studies of iron superoxide dismutases from human parasites
      and a statistical coupling analysis of metal binding specificity.
AB  - Superoxide dismutases (SODs) are a crucial class of enzymes in the combat against
      intracellular free radical damage. They eliminate superoxide radicals by
      converting them into hydrogen peroxide and oxygen. In spite of their very
      different life cycles and infection strategies, the human parasites Plasmodium
      falciparum, Trypanosoma cruzi and Trypanosoma brucei are known to be sensitive to
      oxidative stress. Thus the parasite Fe-SODs have become attractive targets for
      novel drug development. Here we report the crystal structures of FeSODs from the
      trypanosomes T. brucei at 2.0 A and T. cruzi at 1.9 A resolution, and that from
      P. falciparum at a higher resolution (2.0 A) to that previously reported. The
      homodimeric enzymes are compared to the related human MnSOD with particular
      attention to structural aspects which are relevant for drug design. Although the
      structures possess a very similar overall fold, differences between the enzymes
      at the entrance to the channel which leads to the active site could be
      identified. These lead to a slightly broader and more positively charged cavity
      in the parasite enzymes. Furthermore, a statistical coupling analysis (SCA) for
      the whole Fe/MnSOD family reveals different patterns of residue coupling for Mn
      and Fe SODs, as well as for the dimeric and tetrameric states. In both cases, the
      statistically coupled residues lie adjacent to the conserved core surrounding the
      metal center and may be expected to be responsible for its fine tuning, leading
      to metal ion specificity.

PMID- 19384995
TI  - Identifying native-like protein structures with scoring functions based on all
      atom ECEPP force fields, implicit solvent models and structure relaxation.
AB  - Availability of energy functions which can discriminate native-like from non
      native protein conformations is crucial for theoretical protein structure
      prediction and refinement of low-resolution protein models. This article reports
      the results of benchmark tests for scoring functions based on two all-atom ECEPP
      force fields, that is, ECEPP/3 and ECEPP05, and two implicit solvent models for a
      large set of protein decoys. The following three scoring functions are
      considered: (i) ECEPP05 plus a solvent-accessible surface area model with the
      parameters optimized with a set of protein decoys (ECEPP05/SA); (ii) ECEPP/3 plus
      the solvent-accessible surface area model of Ooi et al. (Proc Natl Acad Sci USA
      1987;84:3086-3090) (ECEPP3/OONS); and (iii) ECEPP05 plus an implicit solvent
      model based on a solution of the Poisson equation with an optimized Fast Adaptive
      Multigrid Boundary Element (FAMBEpH) method (ECEPP05/FAMBEpH). Short Monte Carlo
      with-Minimization (MCM) simulations, following local energy minimization, are
      used as a scoring method with ECEPP05/SA and ECEPP3/OONS potentials, whereas
      energy calculation is used with ECEPP05/FAMBEpH. The performance of each scoring
      function is evaluated by examining its ability to distinguish between native-like
      and non-native protein structures. The results of the tests show that the new
      ECEPP05/SA scoring function represents a significant improvement over the earlier
      ECEPP3/OONS version of the force field. Thus, it is able to rank native-like
      structures with C(alpha) root-mean-square-deviations below 3.5 A as lowest-energy
      conformations for 76% and within the top 10 for 87% of the proteins tested,
      compared with 69 and 80%, respectively, for ECEPP3/OONS. The use of the FAMBEpH
      solvation model, which provides a more accurate description of the protein
      solvent interactions, improves the discriminative ability of the scoring function
      to 89%. All failed tests in which the native-like structures cannot be
      discriminated as those with low energy, are due to omission of protein-protein
      interactions. The results of this study represent a benchmark in force-field
      development, and may be useful for evaluation of the performance of different
      force fields.

PMID- 19384996
TI  - Self-guided Langevin dynamics study of regulatory interactions in NtrC.
AB  - Multiple self-guided Langevin dynamics (SGLD) simulations were performed to
      examine structural and dynamical properties of the receiver domain of nitrogen
      regulatory protein C (NtrC(r)). SGLD and MD simulations of the phosphorylated
      active form structure suggest a mostly stable but broad structural ensemble of
      this protein. The finite difference Poisson-Boltzmann calculations of the pK(a)
      values of the active site residues suggest an increase in the pK(a) of His-84 on
      phosphorylation of Asp-54. In SGLD simulations of the phosphorylated active form
      with charged His-84, the average position of the regulatory helix alpha4 is found
      closer to the starting structure than in simulations with the neutral His-84. To
      model the transition pathway, the phosphate group was removed from the
      simulations. After 7 ns of simulations, the regulatory helix alpha4 was found
      approximately halfway between positions in the NMR structures of the active and
      inactive forms. Removal of the phosphate group stimulated loss of helix alpha4,
      suggesting that the pathway of conformational transition may involve partial
      unfolding mechanism. The study illustrates the potential utility of the SGLD
      method in studies of the coupling between ligand binding and conformational
      transitions.

PMID- 19384997
TI  - Building a foundation for structure-based cellulosome design for cellulosic
      ethanol: Insight into cohesin-dockerin complexation from computer simulation.
AB  - The organization and assembly of the cellulosome, an extracellular multienzyme
      complex produced by anaerobic bacteria, is mediated by the high-affinity
      interaction of cohesin domains from scaffolding proteins with dockerins of
      cellulosomal enzymes. We have performed molecular dynamics simulations and free
      energy calculations on both the wild type (WT) and D39N mutant of the C.
      thermocellum Type I cohesin-dockerin complex in aqueous solution. The D39N
      mutation has been experimentally demonstrated to disrupt cohesin-dockerin
      binding. The present MD simulations indicate that the substitution triggers
      significant protein flexibility and causes a major change of the hydrogen-bonding
      network in the recognition strips-the conserved loop regions previously proposed
      to be involved in binding-through electrostatic and salt-bridge interactions
      between beta-strands 3 and 5 of the cohesin and alpha-helix 3 of the dockerin.
      The mutation-induced subtle disturbance in the local hydrogen-bond network is
      accompanied by conformational rearrangements of the protein side chains and bound
      water molecules. Additional free energy perturbation calculations of the D39N
      mutation provide differences in the cohesin-dockerin binding energy, thus
      offering a direct, quantitative comparison with experiments. The underlying
      molecular mechanism of cohesin-dockerin complexation is further investigated
      through the free energy profile, that is, potential of mean force (PMF)
      calculations of WT cohesin-dockerin complex. The PMF shows a high-free energy
      barrier against the dissociation and reveals a stepwise pattern involving both
      the central beta-sheet interface and its adjacent solvent-exposed loop/turn
      regions clustered at both ends of the beta-barrel structure.

PMID- 19384998
TI  - Nanoscale elongating control of the self-assembled protein filament with the
      cysteine-introduced building blocks.
AB  - Self-assembly of artificially designed proteins is extremely desirable for
      nanomaterials. Here we show a novel strategy for the creation of self-assembling
      proteins, named "Nanolego." Nanolego consists of "structural elements" of a
      structurally stable symmetrical homo-oligomeric protein and "binding elements,"
      which are multiple heterointeraction proteins with relatively weak affinity. We
      have established two key technologies for Nanolego, a stabilization method and a
      method for terminating the self-assembly process. The stabilization method is
      mediated by disulfide bonds between Cysteine-residues incorporated into the
      binding elements, and the termination method uses "capping Nanolegos," in which
      some of the binding elements in the Nanolego are absent for the self-assembled
      ends. With these technologies, we successfully constructed timing-controlled and
      size-regulated filament-shape complexes via Nanolego self-assembly. The Nanolego
      concept and these technologies should pave the way for regulated nanoarchitecture
      using designed proteins.

PMID- 19384999
TI  - Chemical synthesis and biotinylation of the thrombospondin domain TSR2.
AB  - The type 1 repeat domain from thrombospondin has potent antiangiogenic activity
      and a structurally interesting fold, making it an attractive target for protein
      engineering. Chemical synthesis is an attractive approach for studying protein
      domains because it enables the use of unnatural amino acids for site-specific
      labeling and detailed structure-function analysis. Here, we demonstrate the first
      total chemical synthesis of the thrombospondin type 1 repeat domain by native
      chemical ligation. In addition to the natural domain, five sites for side chain
      modification were evaluated and two were found to be compatible with oxidative
      folding. Several challenges were encountered during peptide synthesis due to the
      functional complexity of the domain. These challenges were overcome by the use of
      new solid supports, scavengers, and the testing of multiple ligation sites. We
      also describe an unusual sequence-specific protecting group migration observed
      during cleavage resulting in +90 Da and +194 Da adducts. Synthetic access to this
      domain enables the synthesis of a number of variants that can be used to further
      our understanding of the biochemical interaction network of thrombospondin and
      provide insight into the structure and function of this important antitumorogenic
      protein domain.

PMID- 19385000
TI  - Arresting and convicting the innocent: the potential role of an "inappropriate"
      emotional display in the accused.
AB  - Research from both simulated and actual jurors has demonstrated that the
      defendant's emotional display can influence legal decisions. The purpose of this
      paper is to review the evidence regarding the influence of the defendant's
      emotional display, and to consider the potential role of suspect and defendant
      emotion in wrongful convictions. It is possible that the lack of "appropriate"
      emotion during questioning or interrogation may lead investigators to create a
      mind-set that the suspect is the guilty party; as a result, they may be less
      inclined to investigate other leads. During a trial, the defendant's perceived
      level of emotion can potentially mislead jurors (e.g. a defendant displaying a
      low level of emotion leading people to believe, inappropriately, that he is
      guilty). After a review of the pertinent literature and examples of relevant
      cases, reasons are provided regarding why one's emotional display may be of
      limited diagnostic value. Future research ideas are proposed in an effort to
      determine more definitively the impact of the emotional display of the accused on
      legal decisions.

PMID- 19385001
TI  - Reid training and sensitivity to developmental maturity in interrogation: results
      from a national survey of police.
AB  - Although research has demonstrated that youthfulness is a risk factor for
      providing false confessions during criminal interrogations, it is unclear whether
      interrogation training programs address this issue. The goal was to analyze
      differences between Reid-trained (RT) and non-Reid-trained (non-RT) police in
      their sensitivity to the developmental maturity of young suspects. 1,828 police
      officers, 514 of whom were RT, completed surveys about their perceptions and
      practices during interrogation with children, adolescents, or adults. Results
      indicate that, compared with non-RT police, RT police demonstrate less
      sensitivity to the developmental maturity of adolescents in terms of (1)
      perceptions of their competencies during interrogation and (2) use of
      psychologically coercive questioning techniques. These findings have implications
      for the development of juvenile interrogation training programs.

PMID- 19385002
TI  - A high-performance liquid chromatographic analysis and preliminary
      pharmacokinetic characterization of 3'-hydroxypterostilbene in rats.
AB  - A high-performance liquid chromatographic method was developed for the analysis
      of 3'-hydroxypterostilbene. This method involves the use of a Luna C(18) column
      with ultraviolet detection at 325 nm. The mobile phase consisted of acetonitrile,
      water and formic acid (50:50:0.01, v/v/v) with a flow rate of 0.8 mL/min. The
      calibration curves were linear over the range 0.5-100.0 microg/mL. The mean
      extraction efficiency was between 97.40 and 111.16%. The precision of the assay
      was 0.196-14.39% (RSD%), and within 15% at the limit of quantitation (0.5
      microg/mL). The bias of the assay was <16% and within 15% at the limit of
      quantitation. This assay was successfully applied to pre-clinical pharmacokinetic
      samples from rat urine and serum.

PMID- 19385003
TI  - Recent advances in low- and intermediate-1-risk myelodysplastic syndrome:
      developing a consensus for optimal therapy.
AB  - Myelodysplastic syndrome (MDS) is relatively common, with an incidence estimated
      as high as 50 cases per 100,000 people per year. This cancer mainly affects older
      (>or=60 years) patients. MDS refers to a collection of hematologic malignancies
      that share an ineffective production, or hematopoiesis, of normal bone marrow or
      myeloid cells. As progressive bone marrow failure occurs, patients generally
      display gradually worsening cytopenias specific to the type of bone marrow cell
      affected, such as thrombocytopenia or neutropenia. MDS patients often develop
      disease-related anemia requiring chronic blood transfusion; this can lead to
      complications including iron overload. As MDS progresses and the number of bone
      marrow blasts increases, the disease transforms into acute myelogenous leukemia
      (AML). Several classification systems have been developed to identify and
      differentiate particular types of MDS. Proper identification is essential,
      allowing the oncologist to determine prognosis, as well as the optimal
      therapeutic strategy. Several agents have been developed or are under
      investigation for the treatment of MDS, with the therapeutic goal of increasing
      survival and decreasing the rate of AML transformation. Currently, 3 agents are
      FDA-approved: azacitidine, decitabine, and lenalidomide. This clinical roundtable
      will discuss the optimal management of patients with each of these approved
      therapies, as well as the various classification systems used to differentiate
      MDS subtypes for treatment.

PMID- 19385004
TI  - Exposure.  Court upholds time limit on HIV-positive woman's appeal.

PMID- 19385005
TI  - Inmate's HIV exposure claims dismissed.

PMID- 19385007
TI  - Exposure.  Civil commitment for HIV-positive man affirmed.

PMID- 19385006
TI  - Medications.  HIV-positive inmate's deliberate indifference claim dismissed.

PMID- 19385009
TI  - Extended abstracts of the Annual Symposium of the Working Group for Pharmacology
      in Oncology and Hematology (APOH) of the Central European Society for Anticancer
      Drug Research (CESAR). June 12-14, 2008. Gottingen, Germany.

PMID- 19385008
TI  - Accelerative effect of leflunomide on recovery from hepatic fibrosis involves
      TRAIL-mediated hepatic stellate cell apoptosis.
AB  - AIMS: Hepatic fibrosis is reversible, associated with apoptosis of activated
      hepatic stellate cells (HSCs) as injury subsides, thus providing potential
      targets for therapy. Little is known, however, about the course of this
      condition. The objective of this study was to elucidate the mechanism by which
      Kupffer cells regulate HSC biology during regression of hepatic fibrosis and the
      effect of leflunomide on this process. MAIN METHODS: We harvested Kupffer cells
      from rats during spontaneous recovery from liver fibrosis induced by carbon
      tetrachloride (CCl4) and prepared recovery Kupffer cell conditioned medium
      (KCCM). Culture-activated HSCs were pretreated in the absence or presence of
      A771726, the active metabolite of leflunomide, and then stimulated with recovery
      KCCM. KEY FINDINGS: Following stimulation with recovery KCCM, HSCs showed a
      decrease in proliferation and an increase in apoptosis by a caspase-dependent
      mechanism. Furthermore, pretreatment with A771726 markedly enhanced these
      effects. Real-time quantitative PCR (Q-PCR) analysis showed increased expression
      of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Kupffer
      cells during the spontaneous recovery phase. The pro-apoptotic function of KCCM
      prepared from TRAIL siRNA-treated Kupffer cells was obviously decreased,
      suggesting that TRAIL played an important role in recovery from hepatic fibrosis.
      Moreover, A771726 enhanced recovery KCCM-induced apoptosis of HSCs by a mechanism
      involving the inhibition of nuclear factor-kappa B (NF-kappaB) activation.
      SIGNIFICANCE: Our results showed the role of TRAIL in the apoptosis of activated
      HSCs that is induced by Kupffer cells prepared from livers recovering from CCI4
      induced fibrosis and provided insights into the resolution of fibrosis and the
      mechanisms by which leflunomide might act upon liver fibrosis.

PMID- 19385010
TI  - Targeting activated microglia in Alzheimer's pathology by intraventricular
      delivery of a phagocytosable MRI contrast agent in APP23 transgenic mice.
AB  - The role of phagocytosing immune cells in Alzheimer's pathology can be studied
      experimentally in APP23 transgenic mice. This present study intended to label
      phagocytosing immune cells in the plaque periphery of APP23 mice in vivo by
      intraventricular injection of VSOP-C184, a phagocytosable iron oxide nanoparticle
      MRI contrast agent. Firstly, the dosages of 0.1, 1.0 and 10 micromol Fe/kg body
      weight dissolved in 500 nl of artificial cerebrospinal fluid, delivered by
      stereotaxic surgery were evaluated 4 h after surgery in 7 wild type mice using 7
      T MRI. Secondly, the dosage of 1.0 micromol Fe/kg body weight was investigated in
      6 APP23 mice. The distribution of iron oxide particles was evaluated
      histologically. The injection of 0.1 micromol Fe/kg body weight did not result in
      any signal alterations, 10 micromol resulted in strong signal artifacts. The
      delivery of 1.0 micromol Fe/kg body weight in wild type mice resulted in MRI
      signal alterations throughout the ventricular system without large artifacts. It
      was regarded superior to other dosages for the study of the transgenic mice.
      There was no difference in MRI signal alterations and the distribution of iron
      particles in the histology between APP23 and wild type mice using the dosage of
      1.0 micromol Fe/kg body weight. Upon intraventricular injection, the
      phagocytosable contrast agent VSOP-C184 distributes throughout the ventricular
      system, whereas it does not reach the periphery of amyloid plaques in APP23 mice
      in a concentration sufficient to cause MRI signal alterations.

PMID- 19385011
TI  - Thalamo-cortical network pathology in idiopathic generalized epilepsy: insights
      from MRI-based morphometric correlation analysis.
AB  - Epileptic activity underlying idiopathic generalized epilepsy (IGE) is related to
      abnormal thalamo-cortical interactions. Our purpose was to map in vivo the
      organization of the thalamo-cortical network in IGE. We measured cortical
      thickness and thalamic volumes on MRI in 23 IGE patients with generalized tonic
      clonic seizures only and 46 healthy controls. Significant correlations between
      thalamic volumes and cortical thickness were interpreted as thalamo-cortical
      network connections. In controls, thickness of frontal, limbic, and occipital
      regions was positively correlated with the thalamic volumes, corresponding to
      known anatomical connections from sacrificial tracer studies in primates and
      human in vivo DTI data. In patients, thalamo-cortical network correlations
      increased in fronto-central and parietal regions, but decreased in limbic areas.
      Group analysis revealed that, compared to controls, IGE patients had bilateral
      thalamic atrophy and widespread cortical thinning that was most prominent in
      fronto-central areas, with a prevalence of up to 40%. Duration of epilepsy
      affected negatively thalamic volumes and thickness of fronto-central and limbic
      cortices. These effects were significantly different from aging in controls.
      Patients with poorly controlled seizures showed an even faster progression in
      these neocortical regions. Fronto-centro-parietal atrophy in IGE is likely the
      effect of generalized seizure activity inducing thalamo-cortical network
      remodeling. On the other hand, limbic abnormalities may take place secondary to
      thalamic disconnection.

PMID- 19385013
TI  - [Psychiatry and human rights: putting the good of the patient first].

PMID- 19385014
TI  - Understanding gradient artefacts in simultaneous EEG/fMRI.
AB  - Implementation of concurrent functional magnetic resonance imaging (fMRI) and
      electroencephalography (EEG) recording results in the generation of large
      artefacts that can compromise the quality of EEG data. While much effort has been
      devoted towards studying the temporal variation of the artefact waveforms
      produced by time-varying magnetic field gradients, the spatial variation of the
      artefact voltage across EEG leads has not previously been investigated in any
      depth. The aim of this work is to develop an improved understanding of the
      spatial characteristics of the gradient artefacts and the mechanism which
      underlies their generation. This paper therefore presents physical models of the
      artefacts produced by the temporally-varying magnetic field gradients required
      for MRI. Novel analytic expressions for the artefact voltage that account for
      realistic shifts and rotations of the human head were calculated from
      electromagnetic theory, assuming a spherical, homogeneous head and longitudinal
      wirepaths for the EEG cap. These were then corroborated by comparison with
      numerical simulations using actual EEG wirepaths and with experimental
      measurements on an agar phantom and human head. The numerical simulations
      produced accurate reproductions of experimentally measured spatial patterns for
      both the spherical phantom and human head in a variety of orientations and
      gradient fields; correlation coefficients were as high as 0.98 for the phantom
      and 0.95 for the human head. Furthermore, it was determined that artefact
      voltages for both longitudinal and transverse gradients could be decreased by
      adjusting the subject's axial position with respect to the gradient coils. The
      accuracy of the modelled spatial maps along with the ability to model gradient
      artefacts for any given head orientation are a step towards developing improved
      artefact correction algorithms that incorporate motion tracking of the subject
      and selective filtering based on calculated spatial artefact templates, leading
      to greater fidelity in simultaneous EEG/fMRI data.

PMID- 19385012
TI  - Target-specific contrast agents for magnetic resonance microscopy.
AB  - High-resolution ex vivo magnetic resonance (MR) imaging can be used to delineate
      prominent architectonic features in the human brain, but increased contrast is
      required to visualize more subtle distinctions. To aid MR sensitivity to cell
      density and myelination, we have begun the development of target-specific
      paramagnetic contrast agents. This work details the first application of luxol
      fast blue (LFB), an optical stain for myelin, as a white matter-selective MR
      contrast agent for human ex vivo brain tissue. Formalin-fixed human visual cortex
      was imaged with an isotropic resolution between 80 and 150 microm at 4.7 and 14 T
      before and after en bloc staining with LFB. Longitudinal (R1) and transverse (R2)
      relaxation rates in LFB-stained tissue increased proportionally with myelination
      at both field strengths. Changes in R1 resulted in larger contrast-to-noise
      ratios (CNR), per unit time, on T1-weighted images between more myelinated
      cortical layers (IV-VI) and adjacent, superficial layers (I-III) at both field
      strengths. Specifically, CNR for LFB-treated samples increased by 229 +/- 13% at
      4.7 T and 269 +/- 25% at 14 T when compared to controls. Also, additional
      cortical layers (IVca, IVd, and Va) were resolvable in 14 T-MR images of LFB
      treated samples but not in control samples. After imaging, samples were sliced in
      40-micron sections, mounted, and photographed. Both the macroscopic and
      microscopic distributions of LFB were found to mimic those of traditional
      histological preparations. Our results suggest target-specific contrast agents
      will enable more detailed MR images with applications in imaging pathological ex
      vivo samples and constructing better MR atlases from ex vivo brains.

PMID- 19385015
TI  - Robustness of multivariate image analysis assessed by resampling techniques and
      applied to FDG-PET scans of patients with Alzheimer's disease.
AB  - For finite and noisy samples extraction of robust features or patterns which are
      representative of the population is a formidable task in which over
      interpretation is not uncommon. In this work, resampling techniques have been
      applied to a sample of 42 FDG PET brain images of 19 healthy volunteers (HVs) and
      23 Alzheimer's disease (AD) patients to assess the robustness of image features
      extracted through principal component analysis (PCA) and Fisher discriminant
      analysis (FDA). The objective of this work is to: 1) determine the relative
      variance described by the PCA to the population variance; 2) assess the
      robustness of the PCA to the population sample using the largest principal angle
      between PCA subspaces; 3) assess the robustness and accuracy of the FDA. Since
      the sample does not have histopathological data the impact of possible clinical
      misdiagnosis on the discrimination analysis is investigated. The PCA can describe
      up to 40% of the total population variability. Not more than the first three or
      four PCs can be regarded as robust on which a robust FDA can be build. Standard
      error images showed that regions close to the falx and around ventricles are less
      stable. Using the first three PCs, sensitivity and specificity were 90.5% and
      96.9% respectively. The use of resampling techniques in the evaluation of the
      robustness of many multivariate image analysis methods enables researchers to
      avoid over-analysis when using these methods applied to many different
      neuroimaging studies often with small sample sizes.

PMID- 19385017
TI  - Discrimination of the local orientation structure of spiral Glass patterns early
      in human visual cortex.
AB  - The local orientation structure of a visual image is fundamental to the
      perception of spatial form. Reports of reliable orientation-selective modulations
      in the pattern of fMRI activity have demonstrated the potential for investigating
      the representation of orientation in the human visual cortex. Orientation
      selective voxel responses could arise from anisotropies in the preferred
      orientations of pooled neurons due to the random sampling of the cortical
      surface. However, it is unclear whether orientation-selective voxel responses
      reflect biases in the underlying distribution of neuronal orientation preference,
      such as the demonstrated over-representation of radial orientations (those
      collinear with fixation). Here, we investigated whether stimuli balanced in their
      radial components could evoke orientation-selective biases in voxel activity. We
      attempted to discriminate the sense of spiral Glass patterns (opening anti
      clockwise or clockwise), in which the local orientation structure was defined by
      the placement of paired dots at an orientation offset from the radial. We found
      that information within the spatial pattern of fMRI responses in each of V1, V2,
      V3, and V3A/B allowed discrimination of the spiral sense with accuracies
      significantly above chance. This result demonstrates that orientation-selective
      voxel responses can arise without the influence of a radial bias. Furthermore,
      the finding indicates the importance of the early visual areas in representing
      the local orientation structure for the perception of complex spatial form.

PMID- 19385016
TI  - Atlas-based whole brain white matter analysis using large deformation
      diffeomorphic metric mapping: application to normal elderly and Alzheimer's
      disease participants.
AB  - The purpose of this paper is to establish single-participant white matter atlases
      based on diffusion tensor imaging. As one of the applications of the atlas,
      automated brain segmentation was performed and the accuracy was measured using
      Large Deformation Diffeomorphic Metric Mapping (LDDMM). High-quality diffusion
      tensor imaging (DTI) data from a single-participant were B0-distortion-corrected
      and transformed to the ICBM-152 atlas or to Talairach coordinates. The deep white
      matter structures, which have been previously well documented and clearly
      identified by DTI, were manually segmented. The superficial white matter areas
      beneath the cortex were defined, based on a population-averaged white matter
      probability map. The white matter was parcellated into 176 regions based on the
      anatomical labeling in the ICBM-DTI-81 atlas. The automated parcellation was
      achieved by warping this parcellation map to normal controls and to Alzheimer's
      disease patients with severe anatomical atrophy. The parcellation accuracy was
      measured by a kappa analysis between the automated and manual parcellation at 11
      anatomical regions. The kappa values were 0.70 for both normal controls and
      patients while the inter-rater reproducibility was 0.81 (controls) and 0.82
      (patients), suggesting "almost perfect" agreement. A power analysis suggested
      that the proposed method is suitable for detecting FA and size abnormalities of
      the white matter in clinical studies.

PMID- 19385019
TI  - Competing with peers: mentalizing-related brain activity reflects what is at
      stake.
AB  - Competition imposes constraints for humans who make decisions. Concomitantly,
      people do not only maximize their personal profit but they also try to punish
      unfair conspecifics. In bargaining games, subjects typically accept equal-share
      offers but reject unduly small offers; competition affects this balance. Here we
      used functional magnetic resonance imaging (fMRI) to study adjustment to
      competition in a bargaining game where subjects competed against another person
      for a share of the stake. For medium-sized, but not for minimum offers,
      competition increased the likelihood of acceptance and thus shifted behavior
      towards maximizing personal profits, emphasizing the importance of financial
      incentives. Specifically for medium-sized offers, competition was associated with
      increased brain activation bilaterally in the temporo-parietal junction, a region
      associated with mentalizing. In the right inferior frontal region, competition
      related brain activation was strongest in subjects whose high acceptance rates in
      the standard ultimatum game hinted at a profit-oriented approach. The results
      suggest a network of brain areas supporting decision making under competition,
      with incentive-dependent mentalizing engaged when the competitor's behavior is
      difficult to predict and when the stake is attractive enough to justify the
      effort.

PMID- 19385018
TI  - Assessing the effects of age on long white matter tracts using diffusion tensor
      tractography.
AB  - Aging is associated with significant white matter deterioration and this
      deterioration is assumed to be at least partly a consequence of myelin
      degeneration. The present study investigated specific predictions of the
      myelodegeneration hypothesis using diffusion tensor tractography. This technique
      has several advantages over other methods of assessing white matter architecture,
      including the possibility of isolating individual white matter tracts and
      measuring effects along the whole extent of each tract. The study yielded three
      main findings. First, age-related white matter deficits increased gradually from
      posterior to anterior segments within specific fiber tracts traversing frontal
      and parietal, but not temporal cortex. This pattern inverts the sequence of
      myelination during childhood and early development observed in previous studies
      and lends support to a "last-in-first-out" theory of the white matter health
      across the lifespan. Second, both the effects of aging on white matter and their
      impact on cognitive performance were stronger for radial diffusivity (RD) than
      for axial diffusivity (AD). Given that RD has previously been shown to be more
      sensitive to myelin integrity than AD, this second finding is also consistent
      with the myelodegeneration hypothesis. Finally, the effects of aging on select
      white matter tracts were associated with age difference in specific cognitive
      functions. Specifically, FA in anterior tracts was shown to be primarily
      associated with executive tasks and FA in posterior tracts mainly associated with
      visual memory tasks. Furthermore, these correlations were mirrored in RD, but not
      AD, suggesting that RD is more sensitive to age-related changes in cognition.
      Taken together, the results help to clarify how age-related white matter decline
      impairs cognitive performance.

PMID- 19385021
TI  - Effects of 17beta-aminoestrogens on the sexual behavior of female rats.
AB  - 17beta-aminoestrogens (AEs) produce anticoagulant effects in rats contrastingwith
      17beta-estradiol (E2) procoagulant effects, their estrogenic effects are similar
      to E2, decreasing serum luteinizing hormone (LH), increasing uterine weight (Uw),
      activate transcription through the ERalpha and ERbeta receptors and pentolame
      induces progesterone (P) receptors in the anterior pituitary of ovariectomized
      (Ovx) rats similarly to E2, suggesting possible effects on female rats' sexual
      behavior. This work evaluated the AEs prolame, butolame, pentolame compared to E2
      and estradiol benzoate (EB) as facilitators on the rat lordotic behavior. Dose
      response curves were performed in rats by single subcutaneous (s.c.) injection
      (timezero) of: E2 (approximately 0.3, 3, 30, 60, 300 microg/kg); EB
      (approximately 0.4, 4, 40, 80, 400 microg/kg); prolame, butolame, pentolame
      (approximately 40, 400, 2000 or 4000 mg/kg), vehicle (corn oil; 300 microL/day;
      approximately 1.2 mL/kg) as control; 24 h after, P (1 mg/rat in 100 microL of
      corn oil; approximately 4 to 5 mg/kg) was administered, and 5 to 7 h later LQ was
      evaluated (number of lordosis displays/number of mounts x 100). E2, EB and AEs
      followed by P administration, induced lordosis in a dose-dependent manner.
      Prolame induced an LQEmax of 92, butolame85, EB 81, pentolame 44 and E2 43. The
      most potent was EB (LQED50 of 4.1 +/- 0.5 microg/kg); then E2 10 microg +/-
      2.2/kg; prolame 268 +/- 19 microg/kg; butolame 402 +/- 21 microg/kg, and
      pentolame 1037 +/- 28 microg/kg. The AEs LQ potency decreases as length
      substitution on the amine group in C-17 increases. AEs LQDE50 values correlate
      with previous Uw DE50, LH ID50 and binding studies indicates mediation of the
      response by estrogen receptors. AEs facilitate sexual behavior of Ovx rats as
      partial estrogenic agonists.

PMID- 19385020
TI  - Neural recruitment for the production of native and novel speech sounds.
AB  - Two primary areas of damage have been implicated in apraxia of speech (AOS) based
      on the time post-stroke: (1) the left inferior frontal gyrus (IFG) in acute
      patients, and (2) the left anterior insula (aIns) in chronic patients. While AOS
      is widely characterized as a disorder in motor speech planning, little is known
      about the specific contributions of each of these regions in speech. The purpose
      of this study was to investigate cortical activation during speech production
      with a specific focus on the aIns and the IFG in normal adults. While undergoing
      sparse fMRI, 30 normal adults completed a 30-minute speech-repetition task
      consisting of three-syllable nonwords that contained either (a) English (native)
      syllables or (b) non-English (novel) syllables. When the novel syllable
      productions were compared to the native syllable productions, greater neural
      activation was observed in the aIns and IFG, particularly during the first 10 min
      of the task when novelty was the greatest. Although activation in the aIns
      remained high throughout the task for novel productions, greater activation was
      clearly demonstrated when the initial 10 min was compared to the final 10 min of
      the task. These results suggest increased activity within an extensive neural
      network, including the aIns and IFG, when the motor speech system is taxed, such
      as during the production of novel speech. We speculate that the amount of left
      aIns recruitment during speech production may be related to the internal
      construction of the motor speech unit such that the degree of
      novelty/automaticity would result in more or less demands respectively. The role
      of the IFG as a storehouse and integrative processor for previously acquired
      routines is also discussed.

PMID- 19385022
TI  - Dose-dependent satiating effect of whey relative to casein or soy.
AB  - Dietary protein plays a role in body weight regulation, partly because of its
      effects on appetite. The objective was to compare the effects of high or normal
      casein-, soy-, or whey-protein breakfasts on appetite, specific hormones, amino
      acid responses and subsequent energy intake. Twenty-five healthy subjects (mean+/
      SEMBMI:23.9+/-0.3 kg/m2; age:22+/-1 years) received standardized breakfasts:
      custards with either casein-, soy, or whey-protein with either 10/55/35 (normal)
      or 25/55/20 (high)En% protein/carbohydrate/fat in a randomized, single-blind
      design. Appetite profile (Visual Analogue Scales) and amino acid concentrations
      were determined for 4 h whereas plasma glucose, insulin, active Glucagon-like
      Peptide 1 (GLP-1), and active ghrelin concentrations were determined for 3 h; the
      sensitive moment for lunch was determined. Subjects returned for a second set of
      experiments and received the same breakfasts, ad lib lunch was offered 180 min
      later; energy intake (EI) was assessed. At 10En%, whey decreased hunger more than
      casein or soy (p <0.05), coinciding with higher leucine, lysine, tryptophan,
      isoleucine, and threonine responses (p<0.05). At 25En% there were no differences
      in appetite ratings. Whey triggered the strongest responses in concentrations of
      active GLP-1 (p<0.05) and insulin (p<0.05) compared with casein and/or soy. There
      were no differences in EI. In conclusion, differences in appetite ratings between
      different proteins appeared at a normal concentration; at 10En% whey-protein
      decreased hunger more than casein- or soy-protein. At 25En% whey-protein
      triggered stronger responses in hormone concentrations than casein- or soy
      protein. The results suggest that a difference in appetite ratings between types
      of protein appears when certain amino acids are above and below particular
      threshold values.

PMID- 19385023
TI  - Structure of rat behavior in hole-board: II) multivariate analysis of
      modifications   induced by diazepam.
AB  - In our previous study we suggested that multivariate analysis could improve hole
      board test reliability providing a more useful tool to determine behavioral
      effects of anxiolytic drugs. To support this hypothesis, a multivariate analysis
      of rat behavior in hole-board, following administration of the reference
      anxiolytic drug diazepam, was carried out. Four groups, each composed of thirty
      male Wistar rats, were used: one saline and three diazepam injected (0.25, 0.5
      and 2 mg/kg IP). Rat behavior was recorded for 10 min through a digital
      videocamera. Descriptive and multivariate analyses were carried out. In all
      groups, more than 80% of whole behavioral structure encompassed walking,
      climbing, rearing, immobile-sniffing, edge-sniff and head-dip. Moreover,
      modifications observed of a specific index, represented by edge-sniff/head-dip
      ratio, were correlated to diazepam-induced modifications of anxiety level.
      Cluster analysis showed that diazepam at 0.5 and 2 mg/kg induced important
      changes for [edge-sniff/head-dip] cluster. In addition, in all diazepam groups a
      [walking/climbing] cluster appeared. Path diagrams showed close relationships
      among different patterns both in saline and diazepam injected animals. Also,
      significant changes were detected following diazepam for transitions encompassing
      both general exploratory patterns (walking, climbing) and the specific ones (head
      dip and edge-sniff). Adjusted residuals confirmed in all groups patterns
      relationships and, where present, significant behavioral associations. Results
      demonstrate that an anxiolytic activity can be revealed by head-dip/edge-sniff
      association weakening and by the addressing of behavioral structure toward
      general exploratory activity. Improvement of hole-board test reliability in
      behavioral study of anxiety, following multivariate analysis, is emphasized.

PMID- 19385024
TI  - Effects of restrained eating behaviour on insulin sensitivity in normal-weight
      individuals.
AB  - Restrained eating behaviour has been linked to abnormalities in metabolic and
      endocrine functions. However, the impact of restraint on fasting insulin and
      glucose plasma levels and insulin sensitivity remains controversial. Moreover,
      the few postprandial studies to date are limited by an inappropriate sampling
      time frame and a low "net" energy and carbohydrate load. The aims of this study
      are to assess the role of dietary restraint on fasting and postprandial plasma
      levels of insulin, glucose, triacylglycerol (TAG) and non esterified fatty acids
      (NEFA) in healthy volunteers with a normal and stable body weight and to
      determine whether the effect of restraint on the plasma levels of the previous
      hormones/metabolites is load dependent. Normal-weight participants (21 women and
      12 men) were classified as restrained/unrestrained based on the restraint scale
      of the Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour
      Questionnaire. The impact of restraint on the plasma levels of different
      hormones/metabolites was measured, in response to a 500 kcal and 1000 kcal
      breakfast, using a randomised crossover design. Restraint was associated with
      lower fasting insulin plasma levels (P<0.05) and a lower insulin (P<0.015) and
      glucose (P<0.05) plasma levels in the postprandial state, but did not impact on
      TAG or NEFA. Moreover, restrained eaters showed a better fasting (P<0.05) and
      postprandial insulin sensitivity (P<0.01). Restrained eating behaviour has,
      therefore, a significant impact on both fasting and postprandial glucose
      metabolism, being associated with increased insulin sensitivity. These findings
      suggest the need for adjusting for restraint level in studies where glucose
      metabolism is a major outcome.

PMID- 19385025
TI  - EEG activity and mood in health orientated runners after different exercise
      intensities.
AB  - An increasing number of studies within the recent years connected physical
      exercise with changes in brain cortical activity. Most of this data (1) refers to
      aerobic exercise and (2) does not correlate to psychological parameters although
      it is well known that exercise has a positive effect on mood. In times where
      health activities play a major role it is increasingly necessary to connect
      somato-physiological and somatopsychological components of physical activity.
      This study aimed to find changes in EEG activity and mood after low, preferred
      and high intensity running. EEG and actual state of mood were recorded before and
      after exercise. Results showed an effect for the preferred and high intensity
      velocity in both, EEG and mood. As only the higher frequency areas N18 Hz showed
      persisting decreases post-exercise we concluded that this might be a sign of
      outlasting effects of exercise on brain cortical activity which may have
      influences on general well-being. We could also show that there is a clear
      relationship between EEG activity and mood reflecting a basic principle of
      cortical excitation.

PMID- 19385026
TI  - Hedonics of taste influence the gastric emptying in rats.
AB  - It is known that taste sensation plays important roles in various functions
      including appetite, nutriental choices, food intake and digestion. To study the
      modulation of digestive functions by taste stimulation, we measured the gastric
      emptying of experimental foods with appetitive or aversive tastes in Wistar male
      rats. Rats were randomly divided into 3 groups: each group was trained to eat a
      mash mixture (8 g) made up with powdered food (4 g) and a solution (4 g) for 30
      min per day. The solution was either distilled water, saccharin solution as a
      palatable taste, or quinine solution as an aversive taste. On the test day, the
      contents of the stomach of each rat were measured before and 30, 150, or 300 min
      after the start of eating the mash. The results showed that the food output from
      the stomach was increased by the palatable mash and was decreased by the aversive
      mash in comparison with non-adulterated mash 150 min after eating. There were no
      significant differences in gastric emptying among the 3 groups after
      deafferentation of the two peripheral taste nerve branches, the chorda tympani
      and glossopharyngeal nerves, or after intragastric infusions of each mash. After
      the establishment of conditioned taste aversions to saccharin, saccharin mash
      became ineffective in increasing gastric emptying. These results show that
      hedonically positive tastes increase, but hedonically negative tastes decrease
      gastric function in terms of gastric emptying.

PMID- 19385027
TI  - Relationship between perilipin gene polymorphisms and body weight and body  
      composition during weight loss and weight maintenance.
AB  - BACKGROUND: Genetic variation in the perilipin (PLIN) gene may play a role in the
      etiology and treatment of obesity. OBJECTIVE: To examine different polymorphisms
      in the PLIN gene in relation to body-weight regulation. METHODS: 118 subjects
      followed a 6 wk VLCD, followed by 1 year weight maintenance. Body-weight (BW),
      body composition, leptin concentration, and polymorphisms of the PLIN gene:
      PLIN1:rs2289487, PLIN4:rs894160, PLIN6:rs1052700, PLIN5:rs2304795 and PLIN7:rs
      2304796 were determined. RESULTS: BW loss during VLCD was 7.0+/-3.1 kg (p<0.05),
      and BW regain was 3.7+/-1.4 kg (p<0.05), including changes in body mass index
      (BMI), waist-circumference, body-composition and leptin concentrations (p<0.05).
      Linkage disequilibria were observed between PLIN1 and PLIN4: D' >0.9, r2=0.72;
      PLIN5 and PLIN7: D' >0.9, r2=0.85. In men, body weight, BMI, waist circumference,
      body fat, leptin concentrations were significantly lower for the haplotype of
      PLIN1 (C-alleles) and PLIN4 (A-alleles). In women weight loss and loss of fat
      mass were larger for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles).
      For PLIN6 genotypes body weight and body fat were lower for homozygotes of the
      minor allele (T/T) in the men; in the women leptin concentrations were lower. The
      haplotype of PLIN5 and PLIN7 consisting of A/G and G/G of PLIN5 and A/A of PLIN7
      showed a reduction in FM: 5.9+/-0.6 kg vs 3.1+/-0.4 kg, % body fat: 5.5+/-0.6% vs
      2.2+/-0.2%, and leptin: 20.5+/-10.8 ng/ml vs 12.9+/-6.7 ng/ml over time in the
      women (p<0.05). CONCLUSION: Since the haplotype of the minor alleles PLIN1-4,
      PLIN5-7 and PLIN6, was related to body-weight regulation at a lower level of body
      weight in the men as well in the women we conclude that the PLIN1-4, 6, and 5-7
      locus appears as a genetic influencer of obesity risk in humans.

PMID- 19385028
TI  - The free-exploratory paradigm as a model of trait anxiety in rats: test-retest
      reliability.
AB  - The free exploratory paradigm has been proposed as a model of trait anxiety. By
      definition, trait anxiety does not vary from moment to moment, therefore any
      model used to evaluate it needs to give the same results in sequential trials.
      With this in mind, the test-retest reliability of the free-exploratory paradigm
      in rats was evaluated. The behaviour of drug-naive, adult, male, Wistar rats was
      measured in the free-exploratory apparatus on two occasions, either one week
      apart (Experiment I) or four weeks apart (Experiment II). The following
      parameters were evaluated: percentage of time spent in the novel compartment of
      the free exploratory box; percentage of novel compartment units visited;
      percentage of time rearing in the novel compartment; and attempts to enter the
      novel compartment. Subsequently, the intraclass correlation coefficient (ICC) and
      the kappa index (kappa) were calculated for each of these parameters. The
      "percentage of time spent in the novel compartment" was found to be stable over
      time. Analysis of this parameter in Experiment I showed high values of ICC
      (0.805) and kappa (0.716), indicating good reliability with a one-week inter
      trial interval. In Experiment II, although the same parameter's kappa index
      (0.255) failed to show a reasonable test/retest concordance, the ICC value
      (0.760) still demonstrated a good test/retest correlation, suggesting that with a
      four-week inter-trial interval, the reliability may diminish, but still exists.
      Therefore, our results bring further support to the free-exploratory paradigm as
      an animal model of trait anxiety.

PMID- 19385029
TI  - Assessing palatability of long-chain fatty acids from the licking behavior of  
      BALB/c mice.
AB  - Dietary oils such as corn oil, olive oil, and canola oil, which primarily contain
      triacylglycerol and small quantities of fatty acids, are highly palatable to
      animals. In a previous study, we examined the short-term (60 s) licking behavior
      of mice and observed that they exhibited a high licking response to a low
      concentration of fatty acid (linoleic acid), which is comparable to that observed
      for pure corn oil. This finding suggests that fatty acids contribute to the
      palatability of dietary oils. In order to supplement our knowledge of the
      fundamental features of fatty acid palatability in the oral cavity, we assessed
      the licking behavior of BALB/c mice to investigate the palatability of various
      types of long-chain fatty acids. The mice showed high licking responses to 1%
      unsaturated 16- and 18-carbon fatty acids (palmitoleic acid, 16:1; oleic acid,
      18:1; linoleic acid, 18:2; and linolenic acid, 18:3), low licking responses to 16
      and 20-carbon fatty acids (palmitic acid, 16:0 and arachidonic acid, 20:4), and
      no significant response to saturated fatty acids (stearic acid, 18:0 and
      arachidic acid, 20:0) or fatty acid derivatives (methyl linoleate and linole
      alcohol). Additionally, there were differences in the palatability of 18-carbon
      unsaturated fatty acids at very low concentrations. At fatty acid concentrations
      of 0.04% and 0.0625%, the mice showed significant preference for linoleic acid
      and linolenic acid, but not oleic acid, when compared with mineral oil. These
      results suggest that mice show high licking responses to 16- and 18-carbon
      unsaturated long-chain fatty acids at low concentrations. Further, we suggest
      that sensitivity to fatty acids is affected by the saturated state of the fatty
      acid, carbon chain length, and terminal carboxyl group.

PMID- 19385030
TI  - Extracellular calcium protects against verapamil-induced metaphase-II arrest and
      initiation of apoptosis in aged rat eggs.
AB  - Non-specific L-type calcium channel blockers, such as verapamil (> or =50
      microM), induce metaphase-II (M-II) arrest and apoptosis in aged rat eggs
      cultured in Ca(2+)-deficient medium. However, the effects of extracellular Ca(2+)
      on verapamil-induced M-II arrest and apoptosis have not yet been reported. We
      have demonstrated that postovulatory aging induced exit from M-II arrest by
      extruding a second polar body, a morphological sign of spontaneous egg activation
      (SEA). Verapamil inhibited SEA and induced egg apoptosis in a dose-dependent
      manner in Ca(2+)-deficient medium. The initiation of apoptotic features was
      observed at 50 microM of verapamil. Extracellular Ca(2+) (1.80 mM) reduced
      intracellular H2O2 level, bax protein expression, caspase-3 activity, DNA
      fragmentation and protected against 50 microM, but not higher concentrations of >
      or =100 microM in verapamil-induced egg apoptosis. These results suggest that
      extracellular Ca(2+) ions have a role during SEA and protect against verapamil
      induced apoptosis in aged rat eggs.

PMID- 19385031
TI  - Postprandial ghrelin responses are associated with the intermeal interval in  
      time-blinded normal weight men, but not in obese men.
AB  - OBJECTIVE: To investigate the relation between ghrelin responses and meal
      initiation and the effects of BMI and energy status on this. DESIGN: The
      experiment had a randomised, cross-over design. SETTING AND SUBJECTS: Nine normal
      weight (age: 33.2+/-4.8 y, BMI: 23.2+/-0.5 kg/m2) and eleven obese (age: 40.8+/-
      4.7 y, BMI: 33.2+/-0.8 kg/m2) healthy men were recruited from a pool of
      volunteers and by advertisements. INTERVENTIONS: Subjects followed a three-day
      energy restrictive and a three-day energy balanced diet separated by one month.
      Each diet was followed by a time-blinded (overnight) stay at the research
      facility. Subjects received a breakfast (preload) and were instructed to ask for
      lunch when they felt hungry. Ghrelin, insulin, glucose, free fatty acids,
      appetite, IMI and energy intake during lunch were assessed. RESULTS: Postprandial
      decreases in ghrelin (r=-0.54; p<0.05) and the AUC of the ghrelin response (r=
      0.57, p=0.01) were associated with the intermeal interval, independent of diet,
      but in normal weight subjects only. Lunch request was preceded by an increase in
      ghrelin, reaching at least 93% of fasting values. These preprandial increases in
      ghrelin were correlated with IMI, after energy restriction only. Ghrelin
      concentrations but not changes in ghrelin were correlated with appetite.
      CONCLUSION: Meal-related changes in ghrelin are correlated with the IMI in normal
      weight subjects only, independent of diet. Ghrelin concentrations may need to
      reach a certain threshold level before the next meal is initiated.

PMID- 19385032
TI  - Linker histone-like proteins in Muscovy duck (Cairina moschata L) erythrocyte
      chromatin.
AB  - Linker Histone-Like proteins (LHL1 and LHL2) were identified within a linker
      histone complement of Muscovy duck erythrocyte chromatin. Polyacrylamide gel
      electrophoretic patterns of N-bromosuccinimide-cleaved LHL products as well as
      liquid chromatography-electrospray-ion trap mass spectrometry analyses of trypsin
      digested LHL peptides revealed structural similarity of LHL1 to histone H5 and
      between LHL2 and histone H1 subtypes. Since the LHL proteins were stable in the
      presence of 2-mercaptoethanol and dithiothreitol that reduce disulfide bonds, it
      appeared unlikely that this doublet was a thiol-derived product of linker
      histones. A loss of LHL1, with a concomitant maintenance of LHL2 after treatment
      with dilute alkali, seems to suggest that they might represent disparate protein
      conjugates resulting from linker histone modifications through ester linkages.

PMID- 19385033
TI  - Comparative study of DNA damage and repair in head and neck cancer after
      radiation treatment.
AB  - We compared DNA damage and the efficacy of its repair after genotoxic treatment
      with gamma-radiation of lymphocytes and tissue cells isolated from patients with
      squamous cell carcinoma of head and neck (HNSCC) and healthy donors. Thirty-seven
      subjects with HNSCC and 35 healthy donors were enrolled in the study. The extent
      of DNA damage including oxidative lesions and efficiency of the repair were
      examined by alkaline comet assay. HNSCC cancer cells were more sensitive to
      genotoxic treatment and displayed impaired DNA repair. In particular, lesions
      caused by gamma-radiation were repaired less effectively in metastasis of HNSCC
      than in healthy controls. The differences in radiation sensitivity of cancer and
      control cells suggested that DNA repair might be critical for HNSCC treatment. We
      conclude that gamma-radiation might be considered as an effective therapeutic
      strategy for head and neck cancers, including patients in advanced stage of the
      disease with clear evidence of metastasis.

PMID- 19385034
TI  - JNK-binding protein 1 regulates NF-kappaB activation through TRAF2 and TAK1.
AB  - The mitogen-activated protein kinase (MAPK) cascades, including c-Jun N-terminal
      kinase (JNK), are composed of a MAPK, MAPK kinase (MAPKK), and MAPKK kinase
      (MAPKKK). Previously, we reported that JNK-binding protein 1 (JNKBP1) enhances
      JNK activation induced by the TGF-beta-activated kinase1 (TAK1) MAPKKK in
      transfected cells. We have investigated whether JNKBP1 functions as an adaptor
      protein for nuclear factor (NF)-kappaB activation mediated by TAK1 in COS-7
      cells. Co-expression experiments showed that JNKBP1 interacted with not only
      TAK1, but also with its upstream regulators, TNF-receptor associated factors 2
      and 6 (TRAF2 and TRAF6). An endogenous interaction between JNKBP1 and TRAF2 or
      TAK1 was confirmed by immunoprecipitation analysis. We also found that JNKBP1
      could enhance the NF-kappaB activation induced by TAK1 and TRAF2, and could
      promote TRAF2 polyubiquitination. These results suggest a scaffolding role for
      JNKBP1 in the TRAF2-TAK1-NF-kappaB signaling pathway.

PMID- 19385035
TI  - Altered expression of inflammatory cytokine receptors in response to LPS
      challenge through interaction between intestinal epithelial cells and lymphocytes
      of Peyer's patch.
AB  - The intense innate immunological activities occurring at the enteric mucosal
      surface involve interactions between intestinal epithelial cells and immune
      cells. Our previous studies have indicated that Peyer's patch lymphocytes may
      modulate intestinal epithelial barrier and ion transport function in homeostasis
      and host defense via cell-cell contact as well as cytokine signaling. The present
      study was undertaken using the established co-culture system of Caco-2 epithelial
      cells with lymphocytes of Peyer's patch to investigate the expression of IL-8 and
      IL-6 cytokines and cytokine receptors in the co-culture system after challenge
      with Shigella F2a-12 lipopolysaccharide (LPS). The human colonic epithelial cell
      line Caco-2 was co-cultured with freshly isolated lymphocytes from the murine
      Peyer's patch either in the mixed or separated (isolated but permeable
      compartments) co-culture configuration, and was challenged with Shigella F2a-12
      LPS for 8 h. The level of mRNA expressions of human interleukin-8 (hIL-8), human
      interleukin-8 receptor (hIL-8R), mouse interleukin-8 receptor (mIL-8R), mouse
      interleukin-6 (mIL-6), mouse interleukin-6 receptor (mIL-6R) and human
      interleukin-6 receptor (hIL-6R) was examined by semi-quantitative PCR. In both co
      culture groups, hIL-8 expression of Caco-2 cells was decreased, and hIL-8R
      expression was increased compared to the Caco-2 alone group. Upon LPS challenge,
      hIL-8 expression from the Caco-2 cells of both co-culture groups was higher than
      in the Caco-2 control group. The increased hIL-8 expression of Caco-2 cells in
      the separated co-culture group is correlated with a decreased hIL-8R expression
      and an increased mIL-8R expression. In the mixed co-culture group, the increased
      expression of hIL-8 was associated with the upregulated hIL-8R expression on Caco
      2 cells and downregulated mIL-8R on murine Peyer's patch lymphocytes (PPL). mIL-6
      expression from mouse PPL was also upregulated by LPS in mixed co-culture.
      However, upon the treatment with LPS, hIL-6R expression of Caco-2 cells was
      decreased in the mixed co-culture, but increased in separated co-culture. The
      data suggest that release of hIL-8 from epithelial cells may act on lymphocytes
      through a paracrine pathway, but it may also act on the epithelial cells
      themselves via an autocrine pathway. The data also suggest that the release of
      mIL-6 from Peyer's patch lymphocytes affects epithelial cells in a paracrine
      fashion.

PMID- 19385037
TI  - Feed-back regulation of successive meiotic cytokinesis.
AB  - The paper considers a number of abnormal phenotypes with impaired temporal
      regulation of cytokinesis during the meiotic division of pollen mother cells. The
      phenomenon of "non-stop" cytokinesis with blocked arrest of the phragmoplast
      centrifugal motion and cell plate growth as well as incomplete and premature
      cytokinesis are described. The obtained data suggested a model for regulation of
      the processes involved in the arrest of the main cytokinesis processes during its
      completion in the plant meiosis.

PMID- 19385036
TI  - A novel hypothesis regarding the possible involvement of cytosolic phospholipase
      2 in insulin-stimulated proliferation of vascular smooth muscle cells.
AB  - Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells
      (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44
      mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase
      (PI3K). In addition, cytosolic phospholipase 2 (cPLA2) is linked to VSMCs
      proliferation. However, the upstream mechanisms responsible for activation of
      cPLA2 are not well defined. Therefore, this investigation used primary cultured
      rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent
      phosphorylation of cPLA2 and proliferation induced by INS. Exposure of VSMCs to
      INS (100 nM) for 10 min increased the phosphorylation of cPLA2 by 1.5-fold ( p <
      0.01), which was blocked by the cPLA2 inhibitor MAFP (10 microM; 15 min).
      Similarly, the PI3K inhibitor LY294002 (10 microM; 15 min) and ERK1/2 inhibitor
      PD98059 (20 microM; 15 min) abolished the INS-mediated increase in cPLA2
      phosphorylation by 59% (p < 0.001), and by 75% ( p < 0.001), respectively.
      Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS
      stimulated ERK1/2 phosphorylation by 65% ( p < 0.01). Incubation of rat VSMCs
      with INS resulted in an increase of VSMCs proliferation by 85% ( p < 0.001). The
      effect of INS on VSMCs proliferation was significantly ( p < 0.01) reduced by
      pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs
      proliferation via a mechanism involving the PI3K-dependent activation of cPLA2
      and release of arachidonic acid (AA), which activates ERK1/2 and further
      amplifies cPLA2 activity.

PMID- 19385038
TI  - Rat bone marrow derived mesenchymal progenitor cells support mouse ES cell growth
      and germ-like cell differentiation.
AB  - Mouse embryonic fibroblasts (MEFs) have been used as feeder cells to support the
      growth of mouse embryonic stem cell (mESC) and primordial germ cells (PGC) in
      culture for many years. However, MEF preparation is a complex and tedious task.
      Recently, there are reports indicating that the microenvironment provided by bone
      marrow stromal cells could support the survival of embryonic-like stem cells in
      bone marrow. In this report, rat bone marrow derived mesenchymal progenitor cells
      (MPC) were used as feeder cells to culture mouse Oct4-GFP ES cell and ES cell
      derived germ cells. FACS results show that similar to MEF, rat MPC could
      efficiently support growth of the mouse Oct4-GFP ES cell line in culture (MPC
      85.5 +/- 5.1% vs MEF 84.1 +/- 6.2%). ES cells could be subcultured for >15
      passages without losing morphological characteristics. The cultured cells
      expressed stem cell marker alkaline phosphatase, Oct4, Sox2, and SSEA-1.
      Furthermore, rat MPC cells were able to support survival of germ cells isolated
      from mouse Oct4-GFP ES cell formed embryoid bodies (EB). After induction by
      retinoic acid for 7 days, some isolated cells differentiated to spermatogonial
      stem-like cells, expressing Mvh, Stra-8, Hsp90-a, integrinb1 and a6. Compared
      with traditional MEF culture systems, the rat MPC culture system is effective in
      supporting ES cell growth and is easy to prepare.

PMID- 19385040
TI  - Modulation of extracellular matrix turnover in the trabecular meshwork.
AB  - Intraocular pressure (IOP) is the most critical risk factor for primary open
      angle glaucoma (POAG). In most cases of POAG, IOP is increased because of an
      abnormally high aqueous humor outflow resistance in the juxtacanalicular region
      of the trabecular meshwork. A distinct structural change in the trabecular
      meshwork of patients with POAG is the increase in fibrillar extracellular matrix
      in the juxtacanalicular region of the trabecular meshwork. Our knowledge on the
      molecular factors that govern turnover of the extracellular matrix in the
      trabecular meshwork has increased considerably in recent years. It has become
      clear that quality and quantity of the extracellular matrix in the trabecular
      meshwork are regulated by several signaling molecules that interact with each
      other to promote its synthesis, degradation, or extracellular modification.
      Transforming growth factor-beta1 and beta2 (TGF-beta1 and TGF-beta2) which derive
      from the aqueous humor or may be locally expressed induce in cultured trabecular
      meshwork cells the expression of a variety of extracellular matrix molecules. The
      action of TGF-betas very likely requires local activation by thrombospondin-1 and
      is partly mediated by its downstream mediator connective tissue growth factor,
      both of which are constitutively expressed in the trabecular meshwork. Bone
      morphogenetic proteins (BMP)-7 and -4 effectively antagonize the effects of TGF
      beta2 on matrix deposition. The antagonizing effects of BMP-7 are mediated in
      trabecular meshwork cells through Smad7. Smad7 is a key molecular switch to
      inhibit TGF-beta2 signaling in the trabecular meshwork.

PMID- 19385039
TI  - Expression of human uncoupling protein-3 in Drosophila insulin-producing cells
      increases insulin-like peptide (DILP) levels and shortens lifespan.
AB  - Uncoupling proteins (UCPs) can dissipate mitochondrial protonmotive force by
      increasing the proton conductance of the inner membrane and through this effect
      could decrease ROS production, ameliorate oxidative stress and extend lifespan.
      We investigated whether ubiquitous, pan-neuronal or neurosecretory cell-specific
      expression of human UCP3 (hUCP3) in adult Drosophila melanogaster affected
      lifespan. Low, ubiquitous expression of hUCP3 at levels found in rodent skeletal
      muscle mitochondria did not affect proton conductance in mitochondria isolated
      from whole flies, but high pan-neuronal expression of hUCP3 increased the proton
      conductance of mitochondria isolated from fly heads. Expression of hUCP3 at
      moderate levels in adult neurons led to a marginal lifespan-extension in males.
      However, high expression of hUCP3 in neuronal tissue shortened lifespan. The life
      shortening effect was replicated when hUCP3 was expressed specifically in median
      neurosecretory cells (mNSC), which express three of the Drosophila insulin-like
      peptides (DILPs). Expression of hUCP3 in the mNSC did not alter expression of
      dilp2, dilp3 or dilp5 mRNA, but led to increased amounts of DILP2 in fly heads.
      These data suggest that lowering mitochondrial coupling by high expression of
      hUCP3 alters mNSC function in a way that appears to increase DILP-levels in fly
      heads and lead to a concomitant decrease in lifespan.

PMID- 19385041
TI  - Binding kinetics of histone chaperone Chz1 and variant histone H2A.Z-H2B by
      relaxation dispersion NMR spectroscopy.
AB  - The genome of eukaryotic cells is packed into a compact structure called
      chromatin that consists of DNA as well as histone and non-histone proteins.
      Histone chaperones associate with histone proteins and play important roles in
      the assembly of chromatin structure and transport of histones in the cell. The
      recently discovered histone chaperone Chz1 associates with the variant histone
      H2A.Z of budding yeast and plays a critical role in the exchange of the canonical
      histone pair H2A-H2B for the variant H2A.ZH2B. Here, we present an NMR approach
      that provides accurate estimates for the rates of association and dissociation of
      Chz1 and H2A.Z-H2B. The methodology exploits the fact that in a 1:1 mixture of
      Chz1 and H2A.Z-H2B, the small amounts of unbound proteins that are invisible in
      spectra produce line broadening of signals from the complex that can be
      quantified in terms of the thermodynamics and kinetics of the exchange process.
      The dissociation rate constant measured, 22 +/- 2 s(-1), provides an upper bound
      for the rate of transfer of H2A.Z-H2B to the chromatin remodeling complex, and
      the faster-than-diffusion association rate, 10(8) +/- 10(7) M(-1) s(-1),
      establishes the importance of attractive electrostatic interactions that form the
      chaperone-histone complex.

PMID- 19385043
TI  - Structural and functional studies of the biotin protein ligase from Aquifex
      aeolicus reveal a critical role for a conserved residue in target specificity.
AB  - Biotin protein ligase (BPL; EC 6.3.4.15) catalyses the formation of biotinyl-5'
      AMP from biotin and ATP, and the succeeding biotinylation of the biotin carboxyl
      carrier protein. We describe the crystal structures, at 2.4 A resolution, of the
      class I BPL from the hyperthermophilic bacteria Aquifex aeolicus (AaBPL) in its
      ligand-free form and in complex with biotin and ATP. The solvent-exposed beta-
      and gamma-phosphates of ATP are located in the inter-subunit cavity formed by the
      N- and C-terminal domains. The Arg40 residue from the conserved GXGRXG motif is
      shown to interact with the carboxyl group of biotin and to stabilise the alpha-
      and beta-phosphates of the nucleotide. The structure of the mutant AaBPL R40G in
      both the ligand-free and biotin-bound forms reveals that the mutated loop has
      collapsed, thus hindering ATP binding. Isothermal titration calorimetry indicated
      that the presence of biotin is not required for ATP binding to wild-type AaBPL in
      the absence of Mg(2+), and the binding of biotin and ATP has been determined to
      occur via a random but cooperative process. The affinity for biotin is relatively
      unaffected by the R40G mutation. In contrast, the thermodynamic data indicate
      that binding of ATP to AaBPL R40G is very weak in the absence or in the presence
      of biotin. The AaBPL R40G mutant remains catalytically active but shows poor
      substrate specificity; mass spectrometry and Western blot studies revealed that
      the mutant biotinylates both the target A. aeolicus BCCPDelta67 fragment and BSA,
      and is subject to self-biotinylation.

PMID- 19385045
TI  - Annexins--modulators of EGF receptor signalling and trafficking.
AB  - At the cell surface, activation of the epidermal growth factor (EGF) receptor
      triggers a complex network of signalling events that regulate a variety of
      cellular processes. For signal termination, the activated EGF receptor is
      internalised and targeted to lysosomes for degradation. Microdomain localization
      at the plasma membrane and endocytic transport of the EGFR is important for the
      formation of compartment-specific signalling complexes and is regulated by
      scaffolding and targeting proteins. This includes Ca2+-effector proteins, such as
      calmodulin and annexins (Anx), in particular AnxA1, AnxA2, AnxA6 and as shown
      recently,AnxA8. Given that these annexins show differences in their expression
      patterns, subcellular localization and mode of action, they are likely to
      differentially contribute and cooperate in the fine-tuning of EGFR activity. In
      support of this hypothesis, current literature suggests these annexins to be
      involved in different steps that control the endocytic transport and signalling
      of the EGF receptor. This review summarizes how the coordinated activity of
      AnxA1, AnxA2, AnxA6 and AnxA8 can contribute to regulate EGF receptor
      localization and activity.

PMID- 19385042
TI  - Roles and regulation of secretory and lysosomal acid sphingomyelinase.
AB  - Acid sphingomyelinase occupies a prominent position in sphingolipid catabolism,
      catalyzing the hydrolysis of sphingomyelin to ceramide and phosphorylcholine.
      Enzymatic dysfunction of acid sphingomyelinase results in Niemann-Pick disease, a
      lysosomal storage disorder characterized at the cellular level by accumulation of
      sphingomyelin within the endo-lysosomal compartment. Over the past decade
      interest in the role of acid sphingomyelinase has moved beyond its "housekeeping"
      function in constitutive turnover of sphingomyelin in the lysosome to include
      study of regulated ceramide generation. Ceramide functions as a bioactive
      sphingolipid with pleiotropic signaling properties, and has been implicated in
      diverse cellular processes of physiologic and pathophysiologic importance. Though
      many cellular enzymes have the capacity to generate ceramide,there is growing
      appreciation that "all ceramides are not created equal." Ceramides likely exert
      distinct effects in different cellular/subcellular compartments by virtue of
      access to other sphingolipid enzymes (e.g.ceramidases), effector molecules (e.g.
      ceramide-activated protein phosphatases), and neighboring lipids and proteins
      (e.g. cholesterol, ion channels). One of the unique features of acid
      sphingomyelinase is that it has been implicated in the hydrolysis of
      sphingomyelin in three different settings--the endo-lysosomal compartment,the
      outer leaflet of the plasma membrane, and lipoproteins. How a single gene product
      has the capacity to function in these diverse settings, and the subsequent impact
      on downstream ceramide-mediated biology is the subject of this review.

PMID- 19385044
TI  - The washout phenomenon in aqueous outflow--why does it matter?

PMID- 19385046
TI  - A SAXS study of glucagon fibrillation.
AB  - Protein amyloid formation proceeds through a number of different stages.
      Oligomeric species observed at early stages have aroused particular interest
      because of evidence for their involvement in cytotoxic processes such as membrane
      permeabilization. It is unclear whether these oligomers are obligate precursors
      to fibrils or represent "dead-end" species that impede fibrillation. Because of
      the many interconverting species present during amyloid formation, it is
      important to study the process as non-invasively as possible. Small angle X-ray
      scattering (SAXS) measurements allow us to monitor structural changes in solution
      for a population of different species over time. Here, SAXS was used to provide a
      detailed structural description of the fibrillation of the 29 residue peptide
      hormone glucagon at pH 2.5 from the monomer and early oligomers to mature fibers.
      Investigation of the pseudo-equilibrium behavior in the lag phase before
      fibrillation at several concentrations showed that glucagon is present in a
      monomeric form below about 5.1 mg/mL, while larger oligomers with average
      aggregation numbers of about three and seven, are formed at 6.4 and 10.7 mg/mL,
      respectively. Applying several modeling tools to the experimental data, it is
      shown that the early oligomerization states can be described as associations
      between glucagon molecules. After the lag phase, a short rod-like protofibril
      (radius of ~16 A and length >300 A) is formed and subsequently grows to N1000 A
      in length and assembles into long triple-bundled mature fibers. The protofibril
      shares many features with the elongated oligomer proposed to be the structural
      nucleus for insulin fibrils. We propose that on-pathway fibrillar intermediates
      share this elongated shape that easily allows them to be incorporated into mature
      fibrils. This contrasts with the annular shape, which is suggested to be involved
      in cytotoxic membrane permeabilization and may represent a dead-end species off
      the fibrillar pathway.

PMID- 19385047
TI  - TNF-alpha suppressed TGF-beta-induced CTGF expression by switching the binding
      preference of p300 from Smad4 to p65.
AB  - TGF-beta regulates diverse biologic effects including cell growth, cell death or
      apoptosis, cell differentiation, and extracellular matrix (ECM) synthesis.
      Connective tissue growth factor (CTGF), induced by TGF-beta has been reported to
      mediate stimulatory action of TGF-beta-induced ECM. Although TNF-alpha was
      reported to suppress theTGF-beta-induced CTGF gene expression, the molecular
      mechanism is not well clarified. In this study, we found the inhibitory effect of
      TNF-alpha on TGF-beta-induced CTGF expression in WT but not p65-/-MEF cells. TNF
      alpha neither induced Smad7 expression nor affected TGF-beta-induced Smad2
      phosphorylation and nuclear translocation. We demonstrated that p300 physically
      associated with p65 rather than Smad4 in the presence of both TNF-alpha and TGF
      beta. Moreover, the TGF-beta-induced binding of p300 and acetylated H4, but not
      Smad4 to the CTGF promoter was disturbed by TNF-alpha treatment. Overall, our
      data showed that suppression of TNF-alpha on TGF-beta-induced CTGF expression is
      due to the competition of p300 by p65 and Smad4.

PMID- 19385048
TI  - The SOCS box encodes a hierarchy of affinities for Cullin5: implications for
      ubiquitin ligase formation and cytokine signalling suppression.
AB  - The SOCS (suppressors of cytokine signalling) family of proteins inhibits the
      cytokine-induced signalling cascade in part by promoting the ubiquitination of
      signalling intermediates that are then targeted for proteasomal degradation. This
      activity relies upon an interaction between the SOCS box domain, the adapter
      complex elonginBC and a member of the Cullin family, the scaffold protein of an
      E3 ubiquitin ligase. In this study, we dissected this interaction in vitro using
      purified components.We found that all eight SOCS proteins bound Cullin5 but
      required prior recruitment of elonginBC. Neither SOCS nor elonginBC bound Cullin5
      when in isolation. Interestingly, the affinity of each SOCS-elonginBC complex for
      Cullin5 varied by 2 orders of magnitude across the SOCS family. Unexpectedly, the
      most potent suppressors of signalling, SOCS-1 and SOCS-3, bound most weakly to
      the E3 ligase scaffold, with affinities 100- and 10-fold lower, respectively,
      than the rest of the family. The remaining six SOCS proteins all bound Cullin5
      with high affinity (K(d) of ~10 nM) due to a slower off-rate and hence a longer
      halflife of the complex. This difference in affinity may reflect a difference in
      mode of action as only SOCS-1 and SOCS-3 have been shown to suppress signalling
      using both SOCS box-dependent and SOCS box-independent mechanisms. This is not
      the case with the other six SOCS proteins, and our data imply the existence of
      two distinct subclasses of SOCS proteins with a high affinity for Cullin5, the E3
      ligase scaffold, possibly reflecting complete dependence upon ubiquitination for
      suppression of cytokine signalling.

PMID- 19385049
TI  - Concurrent protective and destructive signaling of JNK2 in neuroblastoma cells.
AB  - Investigation of the c-Jun N-terminal kinases (JNKs) has mainly focused on their
      response to stress and their pro-apoptotic effects. In this regard, JNKs are
      crucial mediators of chemotherapy-induced killing of tumor cells. Importantly,
      however, JNKs also have physiological functions in cancer involving cell cycle
      regulation or oncogenesis. Hypothetically, the composition of JNK signalosomes
      determines the signaling outcome which,in turn, implies a multitude of different,
      sometimes opposing and interfering functions. In the present study,the well
      characterized human neuroblastoma cell line SH-SY5Y served as a model system to
      separate physiological and pro-apoptotic JNK actions in the response to the
      cytoskeleton-interfering substances colchicine, cytochalasin D and taxol.
      Basically, JNKs mediated both cell death and proliferation. Using the chemical
      JNK inhibitor SP600125 as well as compartment-specific JNK-inhibiting constructs
      and dominant negative isoform mutants, we show that the nuclear subgroup of JNK2
      is the dominant effector in colchicine and taxol-induced apoptosis, while cell
      cycle promotion is mediated by both cytoplasmic and nuclear JNK2.In contrast,
      cytochalasin D-triggered apoptosis is independent of JNK signaling.
      Interestingly, the data of the present study demonstrate for the first time that
      both cell protective (cell cycle progression) and destructive mechanisms
      (apoptosis) are simultaneously controlled by a single JNK isoform in the same
      cell system even under the influence of one stimulus. This has implications for
      the therapeutic application of JNK inhibitors and cytoskeleton-interfering
      substances in oncologic disorders.

PMID- 19385050
TI  - Functional decreases in P2X7 receptors are associated with retinoic acid-induced 
      neuronal differentiation of Neuro-2a neuroblastoma cells.
AB  - Neuro-2a (N2a) cells are derived from spontaneous neuroblastoma of mouse and
      capable to differentiate into neuronal-like cells. Recently, P2X7 receptor has
      been shown to sustain growth of human neuroblastoma cells but its role during
      neuronal differentiation remains unexamined.We characterized the role of P2X7
      receptors in the retinoic acid (RA)-differentiated N2a cells. RA induced N2a
      cells differentiation into neurite bearing and neuronal specific proteins,
      microtubule-associated protein 2 (MAP2) and neuronal specific nuclear protein
      (NeuN), expressing neuronal-like cells. Interestingly, the RA-induced neuronal
      differentiation was associated with decreases in the expression and function of
      P2X7 receptors. Functional inhibition of P2X7 receptors by P2X7 receptor
      selective antagonists, 5'-triphosphate, periodate-oxidized 2',3'-dialdehyde ATP
      (oATP), brilliant blue G (BBG) or A438079 induced neurite outgrowth. In addition,
      RA and oATP treatment stimulated the expression of neuron-specific class III beta
      tubulin (TuJ1), and knockdown of P2X7 receptor expression by siRNA induced
      neurite outgrowth. To elucidate the possible mechanism, we found the levels of
      basal intracellular Ca2+ concentrations ([Ca2+]i) were decreased in either RA- or
      oATP-differentiated or P2X7receptor knockdown N2a cells. Simply cultured N2a
      cells in low Ca2+ medium induced a 2-fold increase in neurite length. Treatment
      of N2a cells with ATP hydrolase apyrase and the P2X7 receptors selective
      antagonist oATP or BBG decreased cell viability and cell number. Nevertheless,
      oATP but not BBG decreased cell proliferation and cell cycle progression. These
      results suggest for the first time that decreases in expression/function of P2X7
      receptors are involved in neuronal differentiation.We provide additional evidence
      shown that the ATP release-activated P2X7 receptor is important in maintaining
      cell survival of N2a neuroblastoma cells.

PMID- 19385051
TI  - EGF-induced MMP-9 expression is mediated by the JAK3/ERK pathway, but not by  the
      JAK3/STAT-3 pathway in a SKBR3 breast cancer cell line.
AB  - The number of epidermal growth factor receptors (EGFRs) and their ligands are
      highly expressed in malignant tumor cells. The EGF signaling pathway is also
      activated in up to one-third of patients with breast cancer. In this study, we
      investigated the novel function of the JAK3 inhibitor, WHI-P131, on EGF-induced
      MMP-9 expression and the regulatory mechanism of EGF-induced MMP-9 expression in
      SKBR3 cells. We observed that EGF increased MMP-9 mRNA and protein expression in
      a dose-dependent manner. EGF also induced the phosphorylation of EGFR, ERK, and
      STAT-3, and these effects were inhibited by the EGFR inhibitor, AG1478.To
      investigate the involvement of the STAT-3 pathway on EGF-induced MMP-9
      expression, we pretreatedSKBR3 cells with JAK1, JAK2, and JAK3 inhibitors prior
      to EGF treatment. The results showed that the JAK3 inhibitor, WHI-P131, as well
      as JAK3 siRNA transfection, but not the JAK1 and JAK2 inhibitors, significantly
      decreased EGF-induced MMP-9 expression. In addition, EGF-induced STAT-3
      phosphorylation was only inhibited by WHI-P131. We then transfected cells with
      adenoviral STAT-3 (Ad-STAT-3), followed by treatment with EGF. Interestingly, EGF
      induced MMP-9 expression was decreased by Ad-STAT-3 overexpression in a dose
      dependent manner, while it was significantly increased by STAT-3 siRNA
      transfection. Our results also showed that basal levels of MMP-9 expression were
      significantly increased by constitutive active-MEK (CAMEK)overexpression. EGF
      induced ERK phosphorylation was prevented by WHI-P131, but not by JAK1 andJAK2
      inhibitors. On the other hand, EGF-induced MMP-9 expression was decreased by the
      MEK1/2 inhibitor,UO126. Therefore, for the first time, we suggest that the JAK3
      inhibitor, WHI-P131, inhibits EGF-induced STAT-3 phosphorylation as well as ERK
      phosphorylation. The JAK3/ERK pathway may play an important role in EGFinduced
      MMP-9 expression in SKBR3 cells.

PMID- 19385052
TI  - Acta Tropica. Preface.

PMID- 19385053
TI  - Classification, evolution, and species groups within the Triatominae.
AB  - Classification of the Triatominae has become a complex balance between
      traditional approaches and a wide variety of evolutionary interpretations. On the
      one hand is the need for a stable classification of practical use for those
      involved in vector surveillance and control. On the other is the desire to
      adequately reflect evolutionary theory derived from a range of molecular,
      cytogenetic and morphometric comparisons, with additional complications raised by
      current interpretations of the subfamily as a recently derived polyphyletic
      assemblage. Here we review key aspects of triatomine systematics and evolution,
      to derive a pragmatic classification that seeks to build on traditional
      morphological concepts within the context of current evolutionary theories.

PMID- 19385054
TI  - Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis.
AB  - Reactive oxygen species (ROS) have been suggested to be involved in a variety of
      human diseases. Catalase, an enzyme degrading hydrogen peroxide, can be used as a
      therapeutic agent for such diseases, but its successful application will depend
      on the distribution of the enzyme to the sites where ROS are generated. Chemical
      modification techniques have been used to control the tissue distribution of
      catalase, and delivery to hepatocytes (galactosylation), liver nonparenchymal
      cells (mannosylation or succinylation), kidney (cationization) and the blood pool
      (PEGylation) has been achieved. The effectiveness of catalase delivery has been
      demonstrated in animal models for hepatic ischemia/reperfusion injury, chemical
      induced tissue injuries and tumor metastasis to the liver, lung and peritoneal
      organs. Significant inhibition was observed in the ROS-mediated oxidative tissue
      damages and ROS-mediated upregulation of expression of genes responsible for
      recruitment of inflammatory cells and for metastatic growth of tumor cells.
      Because oxygen plays a fundamental key role in our life and oxidative stress is
      implicated in a wide variety of human diseases, catalase delivery could have wide
      application in the near future.

PMID- 19385055
TI  - Isradipine antagonizes hypobaric hypoxia induced CA1 damage and memory 
      impairment: Complementary roles of L-type calcium channel and NMDA receptors.
AB  - Hypobaric hypoxia leads to cognitive dysfunctions due to increase in
      intracellular calcium through ion channels. The purpose of this study was to
      examine the temporal contribution of L-type calcium channels and N-methyl-D
      aspartate receptors (NMDARs) in mediating neuronal death in male Sprague Dawley
      rats exposed to hypobaric hypoxia simulating an altitude of 25,000 ft for
      different durations. Decreasing exogenous calcium loads by blocking voltage-gated
      calcium influx with isradipine (2.5 mg kg(-1)), and its efficacy in providing
      neuroprotection and preventing memory impairment following hypoxic exposure was
      also investigated. Effect of isradipine on calcium-dependent enzymes mediating
      oxidative stress and apoptotic cell death was also studied. Blocking of L-type
      calcium channels with isradipine reduced hypoxia-induced activation of calcium
      dependent xanthine oxidases, monoamine oxidases, cytosolic phospholipase A(2) and
      cycloxygenases (COX-2) along with concomitant decrease in free radical generation
      and cytochrome c release. Increased expression of calpain and caspase 3 was also
      observed following exposure to hypobaric hypoxia along with augmented
      neurodegeneration and memory impairment which was adequately prevented by
      isradipine administration. Administration of isradipine during hypoxic exposure
      protected the hippocampal neurons following 3 and 7 days of exposure to hypobaric
      hypoxia along with improvement in spatial memory.

PMID- 19385056
TI  - CD44 is expressed in non-myelinating Schwann cells of the adult rat, and may play
      a role in neurodegeneration-induced glial plasticity at the neuromuscular
      junction.
AB  - CD44 is a multifunctional cell surface glycoprotein which regulates cell-cell and
      cell-matrix interactions in a variety of tissues. In particular, the protein was
      found to be expressed in glial cells of developing, but not adult, peripheral
      nerves, where it takes part in signaling mediated by ErbB class of receptors for
      neuregulins. Here, we demonstrate, using high resolution morphological methods,
      tissue fractionation and RT-PCR, that CD44 is strongly expressed in terminal
      Schwann cell (TSC) at the neuromuscular junction (NMJ) of the adult rat skeletal
      muscle. As CD44 is also expressed by Schwann cells of the non-myelinated Remak
      bundles of the proximal peripheral nerves, it appears to be a marker of non
      myelinating Schwann cell subpopulation. The analysis of transgenic rats bearing a
      mutated superoxide-dismutase gene (SOD1(G93A)) causing familial amyotrophic
      lateral sclerosis (ALS) revealed that TSC activation and morphological plasticity
      at the NMJ, caused by ongoing denervation-reinnervation is associated with a
      strong increase in CD44 expression therein. Notably, CD44 immunoreactivity is
      present in fine axon-escheating processes of the glial cells that guide
      reinnervation. In addition, we found that both in normal and SOD1(G93A) muscle,
      CD44 expressed in TSC partially colocalizes with immunoreactivities of neuregulin
      receptors ErbB2 and ErbB3. The colocalization appears to reflect a physical
      interaction, as evidenced by co-immunoprecipitation and fluorescence resonance
      energy transfer (FRET) analysis between CD44 and ErbB3. Importantly, TSC
      activation upon ALS-like neurodegeneration results in significant increase in
      molecular proximity of CD44 and ErbB3, which may have an impact on glial
      plasticity at the NMJ.

PMID- 19385057
TI  - KAAD-cyclopamine augmented TRAIL-mediated apoptosis in malignant glioma cells by
      modulating the intrinsic and extrinsic apoptotic pathway.
AB  - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      cancer therapeutic. The main obstacle in TRAIL-based therapy is that many glioma
      cells are resistant. In this study glioblastoma cell lines, human glioblastoma
      short-term cultures and human astrocytes were treated with 3-keto-N
      aminoethylaminoethylcaproyldihydrocinnamoyl cyclopamine (KAAD-cyclopamine),
      tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) or the
      combination of both. Single treatment with KAAD-cyclopamine or TRAIL does not
      induce cytotoxicity in malignant glioma cells. However, treatment with KAAD
      cyclopamine in combination with TRAIL induces rapid apoptosis in TRAIL-resistant
      glioma cells. Notably, normal human astrocytes were not affected by the
      combination treatment consisting of KAAD-cyclopamine and TRAIL. KAAD-cyclopamine
      led to an upregulation of death receptor 4 and 5 and down-regulation of bcl-2 and
      c-FLIP. Furthermore, overexpression of both bcl-2 and c-FLIP attenuated KAAD
      cyclopamine facilitated TRAIL-mediated apoptosis. Taken together,we provided
      evidence that KAAD-cyclopamine facilitated TRAIL-mediated apoptosis at the level
      of the intrinsic and extrinsic apoptotic pathways in malignant glioma cells.

PMID- 19385059
TI  - A highly reproducible rotenone model of Parkinson's disease.
AB  - The systemic rotenone model of Parkinson's disease (PD) accurately replicates
      many aspects of the pathology of human PD and has provided insights into the
      pathogenesis of PD. The major limitation of the rotenone model has been its
      variability, both in terms of the percentage of animals that develop a clear-cut
      nigrostriatal lesion and the extent of that lesion. The goal here was to develop
      an improved and highly reproducible rotenone model of PD. In these studies, male
      Lewis rats in three age groups (3, 7 or 12-14 months) were administered rotenone
      (2.75 or 3.0 mg/kg/day) in a specialized vehicle by daily intraperitoneal
      injection. All rotenone-treated animals developed bradykinesia, postural
      instability, and/or rigidity, which were reversed by apomorphine, consistent with
      a lesion of the nigrostriatal dopamine system. Animals were sacrificed when the
      PD phenotype became debilitating. Rotenone treatment caused a 45% loss of
      tyrosine hydroxylase-positive substantia nigra neurons and a commensurate loss of
      striatal dopamine. Additionally, in rotenone-treated animals, alpha-synuclein and
      poly-ubiquitin positive aggregates were observed in dopamine neurons of the
      substantia nigra. In summary, this version of the rotenone model is highly
      reproducible and may provide an excellent tool to test new neuroprotective
      strategies.

PMID- 19385060
TI  - TGFbeta-induced GRK2 expression attenuates AngII-regulated vascular smooth muscle
      cell proliferation and migration.
AB  - Through diametric actions, the transforming growth factor beta (TGFbeta) and
      Angiotensin II (AngII) play important roles in regulating various biological
      responses such as cell proliferation and migration. Signaling initiated by
      TGFbeta and AngII occurs through two structurally and functionally distinct
      receptor super families,the serine/threonine kinase and G protein-coupled
      receptors (GPCRs). Previously, we identified the Gprotein-coupled receptor kinase
      2 (GRK2), a key regulatory factor in the desensitization of GPCRs, as a direct
      downstream target of the TGFbeta signaling cascade. GRK2 acts through a negative
      feed-back loop mechanism to terminate TGFbeta-induced smad signaling. To
      investigate the impact of TGFbeta-induced GRK2 expression on GPCR signaling, we
      examined its effect on AngII signaling in vascular smooth muscle cells (VSMCs).
      In this study, we show that activation of the TGFbeta signaling cascade in VSMCs
      results in increased GRK2 expression levels, which consequently inhibits AngII
      induced ERK phosphorylation and antagonizes AngII-induced VSMC proliferation and
      migration. Moreover, the inhibitory effect of TGFbeta on AngII signaling occurs
      at the Mek-Erk interface and is abrogated when an anti-sense oligonucleotide
      directed against GRK2 is used. Thus,we conclude that TGFbeta signaling
      antagonizes AngII-induced VSMC proliferation and migration through the inhibition
      of ERK phosphorylation and that GRK2 is a key factor mediating the cross-talk
      between these two receptor super families.

PMID- 19385058
TI  - Anti-PrP Mab 6D11 suppresses PrP(Sc) replication in prion infected myeloid
      precursor line FDC-P1/22L and in the lymphoreticular system in vivo.
AB  - The pathogenesis of prion diseases is related to conformational transformation of
      cellular prion protein (PrP(C)) into a toxic, infectious, and self-replicating
      conformer termed PrP(Sc). Following extracerebral inoculation, the replication of
      PrP(Sc) is confined for months to years to the lymporeticular system (LRS) before
      the secondary CNS involvement results in occurrence of neurological symptoms.
      Therefore, replication of PrP(Sc), in the early stage of infection can be
      targeted by therapeutic approaches, which like passive immunization have limited
      blood-brain-barrier penetration. In this study, we show that 6D11 anti-PrP
      monoclonal antibody (Mab) prevents infection on a FDC-P1 myeloid precursor cell
      line stably infected with 22L mouse adapted scrapie strain. Passive immunization
      of extracerebrally infected CD-1 mice with Mab 6D11 resulted in effective
      suppression of PrP(Sc) replication in the LRS. Although, a rebound of PrP(Sc)
      presence occurred when the Mab 6D11 treatment was stopped, passively immunized
      mice showed a prolongation of the incubation period by 36.9% (pb0.0001) and a
      significant decrease in CNS pathology compared to control groups receiving
      vehicle or murine IgG. Our results indicate that antibody-based therapeutic
      strategies can be used, even on a short-term basis, to delay or prevent disease
      in subjects accidentally exposed to prions.

PMID- 19385061
TI  - Impaired astrocytic gap junction coupling and potassium buffering in a mouse
      model of tuberous sclerosis complex.
AB  - Abnormalities in astrocytes occur in the brains of patients with Tuberous
      Sclerosis Complex (TSC) and may contribute to the pathogenesis of neurological
      dysfunction in this disease. Here, we report that knock-out mice with Tsc1 gene
      inactivation in glia (Tsc1(GFAP)CKO mice) exhibit decreased expression of the
      astrocytic connexin protein, Cx43, and an associated impairment in gap junction
      coupling between astrocytes. Correspondingly, hippocampal slices from
      Tsc1(GFAP)CKO mice have increased extracellular potassium concentration in
      response to stimulation. This impaired potassium buffering can be attributed to
      abnormal gap junction coupling, as a gap junction inhibitor elicits an additional
      increase in potassium concentration in control, but not Tsc1(GFAP)CKO slices.
      Furthermore, treatment with a mammalian target of rapamycin inhibitor reverses
      the deficient Cx43 expression and impaired potassium buffering. These findings
      suggest that Tsc1 inactivation in astrocytes causes defects in astrocytic gap
      junction coupling and potassium clearance, which may contribute to epilepsy in
      Tsc1(GFAP)CKO mice.

PMID- 19385062
TI  - Forskolin increases angiogenesis through the coordinated cross-talk of  PKA
      dependent VEGF expression and Epac-mediated PI3K/Akt/eNOS signaling.
AB  - Forskolin, a potent activator of adenylyl cyclases, has been implicated in
      modulating angiogenesis, but the underlying mechanism has not been clearly
      elucidated. We investigated the signal mechanism by which forskolin regulates
      angiogenesis. Forskolin stimulated angiogenesis of human endothelial cells and in
      vivo neovascularization, which was accompanied by phosphorylation of CREB, ERK,
      Akt, and endothelial nitric oxide synthase (eNOS) as well as NO production and
      VEGF expression. Forskolin-induced CREB phosphorylation, VEGF promoter activity,
      and VEGF expression were blocked by the PKA inhibitor PKI.Moreover,
      phosphorylation of ERK by forskolin was inhibited by the MEK inhibitor PD98059,
      but not PKI. The forskolin-induced Akt/eNOS/NO pathway was completely inhibited
      by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, but not
      significantly suppressed by PKI. These inhibitors and a NOS inhibitor partially
      inhibited forskolin-induced angiogenesis. The exchange protein directly activated
      by cAMP (Epac) activator, 8CPT-2Me-cAMP, promoted the Akt/eNOS/NO pathway and ERK
      phosphorylation,but did not induce CREB phosphorylation and VEGF expression. The
      angiogenic effect of the Epac activator was diminished by the inhibition of PI3K
      and MEK, but not by the PKA inhibitor. Small interfering RNA-mediated knockdown
      of Epac1 suppressed forskolin-induced angiogenesis and phosphorylation of ERK,
      Akt, and eNOS, but not CREB phosphorylation and VEGF expression. These results
      suggest that forskolin stimulates angiogenesis through coordinated cross-talk
      between two distinct pathways, PKA-dependent VEGF expression and Epac-dependent
      ERKactivation and PI3K/Akt/eNOS/NO signaling.

PMID- 19385063
TI  - Cannabinoids attenuate the effects of aging upon neuroinflammation and
      neurogenesis.
AB  - WIN-55,212-2 (WIN-2) can elicit anti-inflammatory and cognitive-enhancing effect
      in aged rats. The current study was designed to determine the differential role
      of the endocannabinoid receptor sub-types 1 (CB1) and 2 (CB2) and transient
      receptor potential vanilloid 1 receptor (TRPV1) in the reduction of age
      associated brain inflammation and their effects on neurogenesis in the dentate
      gyrus of aged rats. Our results demonstrate that 1) the antagonist actions of WIN
      2 at the TRPV1 receptor are responsible for the reduction in microglial
      activation and 2) the agonist actions of WIN-2 at CB1/2 receptors can trigger
      neurogenesis in the hippocampus of aged rats. Chronic treatment with WIN-2
      established an anti-inflammatory cytokine profile within the hippocampus. Our
      results provide insight into the role of the endocannabinoid and vanilloid
      systems upon two different and detrimental aspects of normal and pathological
      aging, chronic neuroinflammation and decline in neurogenesis.

PMID- 19385064
TI  - Loss-of-function point mutations and two-furin domain derivatives provide
      insights  about R-spondin2 structure and function.
AB  - R-spondins (Rspos) potentiate Wnt/beta-catenin signaling, an important pathway in
      embryonic development that is constitutively active in many cancers. To analyze
      Rspo structure and function, we expressed full-length wild-type Rspo2 and Rspo2
      point mutants corresponding to Rspo4 variants that have been linked to
      developmental defects. The Rspo2 mutants had markedly reduced potency relative to
      the wild-type protein,demonstrating for the first time specific amino acid
      residues in Rspos that are critical for beta-catenin signaling. The diminished
      activity of Rspo2/C78Y and Rspo2/C113R was attributable to a defect in their
      secretion, while Rspo2/Q70R exhibited a decrease in its intrinsic activity.
      Cysteine assignments in a Rspo2 derivative containing only the two furin-like
      domains (Rspo2-2F) provided the first information about the disulfide bonding
      pattern of this motif, which was characterized by multiple short loops and
      unpaired cysteine residues, and established that the loss-of-function cysteine
      mutants disrupted disulfide bond formation. Moreover, Rspo2-2F demonstrated
      potent activity and synergized strongly with Wnt-3a in a beta-catenin reporter
      assay. In contrast, an Rspo2-2F derivative containing the Q70R substitution
      showed significantly reduced activity, although it still synergized with Wnt-3a
      in the reporter assay. Rspo2-2F derivatives elicited an unusually sustained
      phosphorylation (20 h) of the Wnt co-receptor, low density lipoprotein receptor
      related protein 6 (LRP6), as well as an increase in cell surface LRP6. Co
      immunoprecipitation experiments involving LRP6 and Kremens suggested that these
      associations contribute to Rspo2 activity, although the lack of major differences
      between wild-type and Q70R derivatives implied that additional interactions may
      be important.

PMID- 19385065
TI  - Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects
      in Finnish variant late infantile NCL.
AB  - Finnish variant LINCL (vLINCL(Fin)) is the result of mutations in the CLN5 gene.
      To gain insights into the pathological staging of this fatal pediatric disorder,
      we have undertaken a stereological analysis of the CNS of Cln5 deficient mice
      (Cln5-/-) at different stages of disease progression. Consistent with human
      vLINCL(Fin), these Cln5-/- mice displayed a relatively late onset regional
      atrophy and generalized cortical thinning and synaptic pathology, preceded by
      early and localized glial responses within the thalamocortical system. However,
      in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in
      the cortex and only subsequently occurred within thalamic relay nuclei.
      Nevertheless, as in other NCL mouse models, this progressive thalamocortical
      neuron loss was still most pronounced within the visual system. These data
      provide unexpected evidence for a distinctive sequence of neuron loss in the
      thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in
      other forms of NCL.

PMID- 19385066
TI  - Nuclear PLCbeta1 is required for 3T3-L1 adipocyte differentiation and regulates
      expression of the cyclin D3-cdk4 complex.
AB  - A phosphoinositide signalling cycle is present in the nucleus, independent of
      that which occurs at the plasma membrane. The key enzyme involved in this cycle
      is phospholipase (PLC) beta1. This nuclear cycle has been shown to be involved in
      both cell proliferation and differentiation. Here, we report that nuclear
      PLCbeta1 activity is upregulated during differentiation of 3T3-L1 adipocytes.
      During differentiation there are two phases of PLCbeta1 activity; the first
      occurs within 5 min of treatment with differentiation media, does not require new
      PLCbeta1 to enter the nucleus and is regulated by pERK and PKC alpha while the
      second phase occurs from day 2 of differentiation, requires new PLCbeta1 protein
      to enter the nucleus and is independent of regulation by pERK and PKC alpha. Over
      expression with the PLC mutants, Deltamk (which lacks the ERK phosphorylation
      site) and M2B (which lacks the nuclear localisation sequence), revealed that both
      phases of PLCbeta1 activity are required for terminal differentiation to occur.
      Inhibition of PLCbeta1 activity prevents the upregulation of cyclinD3 and cdk4
      protein, suggesting that PLCbeta1 plays a role in the control of the cell cycle
      during differentiation. These results indicate nuclear PLCbeta1 as a key
      regulator of adipocyte differentiation.

PMID- 19385067
TI  - Usefulness of Adams-Harbertson protein precipitation-based wine tannin method.

PMID- 19385068
TI  - [On 100th anniversary since birthday of Andrei Dmitrievich Ado].

PMID- 19385069
TI  - [Overcoming of a tissue barrier by allergens--a key form of predisposition to
      allergy].

PMID- 19385070
TI  - [Pathogenetic correlations between pathomorphological disorders and activation of
      lipoperoxidation in endotoxicosis].

PMID- 19385071
TI  - [Endotoxemia in hemorrhagic hypotension].

PMID- 19385072
TI  - [Tuberculosis morbidity in the Republic of Kazakhstan under new economic
      conditions].
AB  - The impact of economic reformation on the incidence of tuberculosis has been
      studied in the Republic of Kazakhstan under new economic conditions. The highest
      tuberculosis morbidity rate regions have identified. The level of income is given
      by the country's regions and the lowest tuberculosis morbidity rate is shown in
      the best financial regions. The author shows that despite the fact that in the
      past years the socioeconomic indices have improved in the Republic of Kazakhstan
      as a whole, but in not all population groups they are increasing equally. The
      incomes of pensioners, unemployed, and workers of the budgetary sector remain
      low, causing a significant increase in the morbidity of tuberculosis in these
      social groups. The author notes that reducing the incidence of tuberculosis
      primarily requires improvement of the mechanisms of social protection (including
      the increase of the efficiency of provision of the most socially vulnerable
      strata with drugs).

PMID- 19385073
TI  - [Biologic age as a criterion for work evaluation (exemplified by titanium alloys
      production)].
AB  - The article deals with results of studies concerning biologic age of workers
      (males) under occupational hazards of titanium alloys (jeopardy classes 3.3,
      3.4.4) in Verkhne-Saldinsky metallurgic production association. Based on
      mathematic statistic analysis, the authors worked out an equation of multiple
      regression for ageing pace to forecast the ageing with consideration of age,
      length of service, occupation. The authors determined occupational groups
      characterized by premature ageing and increased risk of health disorders.

PMID- 19385074
TI  - [Work conditions and occupational morbidity in workers of aluminium production
      enterprises].
AB  - The article covers analysis of work conditions for aluminium plant workers,
      through workplaces certification. The authors specified work condition classes
      according to the jeopardy degree. Number of workplaces with conditions having
      occupational hazards' MAC and MAL excess 10-fold and over (class 3.3 and 3.4)
      approached 30%. Materials on occupational morbidity in 9 aluminium plants over
      recent 6 years are presented, with parameters and structure of the morbidity.
      Findings are that 60.4% of the occupational diseases are diagnosed among
      electrolysis workers with average length of service of 26.3 years. Results of the
      workplaces certification are compared in accordance with work conditions and
      occupational morbidity parameters.

PMID- 19385075
TI  - [Related to age and length of service, changes in psycho-physiologic
      occupationally important traits of technologic processes operators].
AB  - Psycho-physiologic occupational fitness of technologic processes operators
      changes during long-standing work in the occupation. The changes are age-related.
      Over 50 years of age, attention and mental performance do not satisfy the level
      required, so occupational fitness should be re-assessed after 50 years of age.

PMID- 19385076
TI  - [Life quality of workers in machinery plants of Moscow region].
AB  - Questionnaires SF-36 and NJ-29 were used to examine 107 workers including 33 ones
      exposed to vibration, 27 ones - to various hazards mostly chemical, and 47
      individuals without any exposure. Life quality corresponding to normal was
      pointed out by 80.4% of the examinees throughout the whole select, but the
      minimal one - by 75.8 % of the workers exposed to vibration. The latter group
      examinees had lower life quality in Pain scale (76 points), General Health scale
      (60.51), Vitality (63.3), Social functioning (72 points). In all the groups,
      psychic health was decreased, according to self-estimation of the examinees
      (69.01; 75.26; 71.92). The authors recommend inclusion of Questionnaire SF-36
      into examination methods in periodic medical workups.

PMID- 19385077
TI  - [The curative preventive care to population of the Russian Federation in 2007:
      resource supply and functioning major indicators].

PMID- 19385078
TI  - [The rural families' morbidity and its modeling].
AB  - The research data revealed on the regional level the increase of differences in
      the life-style and health state between urban and rural population and social
      groups as well. The implementation of the mathematical modeling contributed to
      the elaboration of three mathematical patterns providing the prospective
      forecasting of morbidity in the full rural families dwelling on different
      territories. The traits of similarity and substantial distinctions in the
      development of full rural families' morbidity on the level of industrial, agro
      industrial and agrarian territories. The conclusion is made about the necessity
      of management of health in rural population on the individual familial and
      regional levels.

PMID- 19385079
TI  - [The organization of medical maintenance of patients with circulatory system
      pathology].

PMID- 19385080
TI  - [The organizational issues of the blood transfusion service operation].
AB  - The data on the security maintenance of blood, its components and preparations is
      presented. The issues of blood plasma quarantinization period are discussed. The
      results of plasma culling as a consequence of second donor non-attendance and
      second examination of fresh-frozen blood plasma are discussed. It is mentioned
      that it would be appropriate to expose to inactivation and to virus elimination
      the blood plasma which has to be a subject to destruction for one or another
      reason. At the same time it is preferably to apply the technology of virus
      inactivation of the fresh-frozen blood plasma utilizing the technique of solvent
      detergent agents processing of blood plasma.

PMID- 19385081
TI  - [The medical dosimetric registry as a health assessment tool in persons submitted
      to the radiative exposure].
AB  - The technique of medical dosimetric registry elaboration aimed to generating the
      registration groups according to the radiative exposure degree was developed by
      the example of the Federal target program "The Semipalatinsk proving ground
      Altai". The diseases' prevalence rates among various dispanserization groups in
      2007 has been calculated. It is established that in different registration groups
      of registry the prevalence of particular kinds of pathology differs
      significantly. The mortality indicators has been calculated as well. The diseases
      of circulatory system are established as the major cause of mortality among the
      observed contingent followed by the neoplasms. The neoplasms' mortality level
      among males is higher in comparison with females.

PMID- 19385082
TI  - [The diagnostic services in the Omsk medical health care institutions].
AB  - The analysis of the medical diagnostic services status in the city of Omsk is
      presented based on the study of the opinions of the medical specialists from
      various municipal medical health care institutions. The research results validity
      is proved by the implementation of the fitting criterion conjointly with its
      reliability evaluation.

PMID- 19385083
TI  - [The role of school medical nurse in the organization of visual impairment
      prevention among school students].

PMID- 19385084
TI  - [The Odessa physicians society and the development of emergency care service in
      the onset of twentieth century].

PMID- 19385086
TI  - Doctors still learning from pig brain disorder.

PMID- 19385085
TI  - Egr-1 is involved in the inhibitory effect of leptin on PPARgamma expression in
      hepatic stellate cell in vitro.
AB  - AIMS: Hepatic stellate cell (HSC) activation is a key step in the hepatic
      fibrogenic process. Increasing evidence demonstrates the pro-fibrogenic action of
      leptin in rodent liver. Peroxisome proliferator-activated receptor-gamma
      (PPARgamma) is a potential molecular target for inhibition of HSC activation. Our
      previous study suggested that leptin markedly down-regulated PPARgamma gene
      expression in HSCs. The aim of this study is to explore the molecular mechanisms
      underlying the inhibitory effect of leptin on PPARgamma expression in rat HSCs in
      vitro. MAIN METHODS: The effects of leptin on the expression and trans-activation
      activity of early growth response-1 (Egr-1) are examined by using real-time PCR,
      Western blotting analysis, transient transfection, and electrophoretic mobility
      shift assay. The role of Egr-1 in PPARgamma gene expression is demonstrated by co
      transfection approach, Western blotting analysis and real-time PCR. KEY FINDINGS:
      We document that leptin increases Egr-1 expression at protein and mRNA levels,
      and significantly stimulates Egr-1 trans-activation activity. Moreover, leptin
      induces the expression and activity of Egr-1 through activation of extracellular
      signal-regulated kinase (ERK) or phosphatidylinositol 3-kinase/AKT signaling (PI
      3K/AKT) pathway. Further investigation reveals that Egr-1 exerts a clear
      inhibitory effect on the promoter activity and expression of PPARgamma gene and
      demonstrates that Egr-1 increases the expression of HSC activation markers and
      promotes HSC growth. Taken together, these findings suggest that Egr-1 is
      involved in the inhibitory effect of leptin on PPARgamma expression in rat HSCs
      in vitro. SIGNIFICANCE: Our results provide novel insights into the mechanisms of
      leptin-induced inhibition of PPARgamma expression in HSCs in vitro.

PMID- 19385087
TI  - HIV policy: the path forward--a joint position paper of the HIV Medicine
      Association of the Infectious Diseases Society of America and the American
      College of Physicians.

PMID- 19385089
TI  - Perception of 3D shape in context: contrast and assimilation.
AB  - Whereas integration of shape and surround is held to occur through cue-dependent
      representations, we show that both cue-invariant and cue-dependent
      representations are involved. A central hinged plane and larger flanking plane
      were defined by either binocular disparity or motion. In a 'within-cue'
      condition, shape and surround were defined by the same cue and in a 'cross-cue'
      condition they were defined by a different cue. Observers compared the dihedral
      angle of the central shape with a constant reference. When the central shape was
      defined by disparity, the surround stimuli invoked a contrast bias in the within
      cue condition, but shape assimilation occurred in the cross-cue condition. When
      the central shape was defined by motion there were overall no significant
      results, but if a contrast bias was observed, it was in the within-cue condition
      where integration could occur through cue-dependent representations.

PMID- 19385088
TI  - Attention trades off spatial acuity.
AB  - Covertly attending to a stimulus location increases spatial acuity. Is such
      increased spatial acuity coupled with a decreased acuity at unattended locations?
      We measured the effects of exogenous (transient and involuntary) and endogenous
      (sustained and voluntary) attention on observers' acuity thresholds for a Landolt
      gap resolution task at both attended and unattended locations. Both types of
      attention increased acuity at the attended and decreased it at unattended
      locations relative to a neutral baseline condition. These trade-off findings
      support the idea that limited processing resources affect early vision, even when
      the display is impoverished and there is no location uncertainty. There was no
      benefit without a cost.

PMID- 19385090
TI  - Thioredoxin 1 delivery as new therapeutics.
AB  - Thioredoxin 1 (Trx 1) is a redox-active small protein ubiquitously present in
      human body. It is one of the defensive proteins induced in response to various
      stress conditions. In addition to its anti-oxidative effect by dithiol-disulfide
      exchange in its active site, Trx 1 has anti-apoptotic and anti-inflammatory
      effects. Trx 1 overexpression has been shown to be effective in a wide variety of
      animal models for oxidative and inflammatory disorders. An administration of
      recombinant Trx 1 protein is also effective in animal models especially for
      severe acute lung diseases where Trx 1 is likely to act with its anti
      inflammatory properties. Trx 1 in circulation shows anti-chemotactic effects for
      neutrophils and inhibitory effects against macrophage migration inhibitory factor
      (MIF). Neovascularization is also suppressed by Trx 1 via inhibition of the
      complement activation. Here we discuss precise mechanisms of Trx 1 and potential
      therapeutic approach of this molecule.

PMID- 19385091
TI  - Design and development of dendrimer photosensitizer-incorporated polymeric
      micelles for enhanced photodynamic therapy.
AB  - Photodynamic therapy (PDT), which involves systemic administration of
      photosensitizers (PSs) followed by local photoillumination, is a promising method
      for the treatment of solid tumors and other diseases. Recently, considerable
      efforts have been devoted to the development of nanocarriers for the PS delivery
      with the aim of avoiding non-specific phototoxicity to normal tissues such as the
      skin. Here, we discuss the biological significance of the use of nanocarrier
      encapsulated PSs in PDT. Also, we report our recent achievements on the
      development of dendrimer photosensitizer-loaded micelles as nanocarriers for PS
      delivery. We found that our nanocarriers greatly enhanced the PDT efficacy in
      vitro and in vivo, and also significantly reduced the skin phototoxicity. These
      results indicate the importance of a development strategy for nanocarriers and
      their great potential for clinical use. In addition, this review discusses the
      development of nanocarriers for emerging PDT-related technologies such as
      photodynamic diagnosis (PDD) and photochemical internalization (PCI).

PMID- 19385092
TI  - Effects of nitrite on modulating ROS generation following ischemia  and
      reperfusion.
AB  - It has long been known that the generation of reactive oxygen species (ROS) is a
      major cause of injury after ischemia/reperfusion. More recently it has emerged
      that the predominant source of these ROS are the mitochondria, which are
      specifically damaged during prolonged ischemic episodes. Several strategies have
      been tested to attenuate mitochondrial damage and reperfusion ROS. Most
      successful has been ischemic preconditioning, a procedure in which repetitive
      short periods of ischemia and reperfusion reduce injury from a subsequent
      prolonged ischemia and reperfusion. Recently, ischemic postconditioning, whereby
      reperfusion after prolonged ischemia is repetitively interrupted for a short
      period, has also been shown to equally protect as ischemic preconditioning. Both
      procedures activate the same down-stream kinase pathways that minimize apoptosis
      and tissue damage. Endothelial nitric oxide synthase is a target of these kinase
      pathways and nitric oxide (NO) administration can mimic its protective effect.
      However, the optimal NO dose is difficult to determine and excess NO levels have
      been shown to be detrimental. A recently described physiological storage pool of
      NO, nitrite, has been shown to be a potent mediator of cytoprotection after
      ischemia/reperfusion that mechanistically reduces mitochondrial ROS generation at
      reperfusion. Here, we describe the sources, bioactivaton, and mechanisms of
      action of nitrite and discuss the potential of this simple anion as a therapeutic
      to protect against ischemia/reperfusion injury.

PMID- 19385093
TI  - [Population, disease, and demographic change, 1537-1636: a critical look at the
      historical demography of Tunja].

PMID- 19385094
TI  - [Drinks and social environment in 19th-century Cuba].

PMID- 19385095
TI  - [The case against Juan Vazquez, a healer from Cajamarca, in 1710: a revealing
      study].

PMID- 19385096
TI  - ["Assisting the poor for free": the medical profession in colonial Jujuy].

PMID- 19385097
TI  - Donor age-dependent acceleration of cellular aging by  repeated ultraviolet A
      irradiation of human dermal  fibroblasts derived from a single donor.
AB  - The relationship between cellular aging and aging of entire organisms has been
      studied extensively.The findings are confusing, however, and no clear
      relationships have been demonstrated.The conflicting data may be due to
      individual differences among the donors of the studied cells.It is crucial to
      identify the changes in cellular properties that are the result of the aging
      process.Here, we used human dermal fibroblast cell lines established from a
      single donor at different ages to assess the influence of ultraviolet A (UVA) on
      cellular aging. These cell lines have the same genetic background and were
      obtained from a restricted body region. The results indicated that cellular aging
      was accelerated by UVA irradiation in a donor age-dependent manner. The ratio of
      lifespan shortening increased with donor age. Increased donor age not only
      decreased cell division, but also increased the growth arrest response to UVA
      irradiation. The characteristics of the cultured cells reflected the age-related
      changes in dermal fibroblasts.

PMID- 19385098
TI  - Donor age reflects the replicative lifespan of human  fibroblasts in culture.
AB  - Human fibroblasts, which have a finite lifespan in cultures, have been widely
      used as a model system for cellular aging, and frequently used as one model of
      human aging. But whether cellular aging contributes to organismal aging has been
      controversial. To reinvestigate this question, we cultured human fibroblasts from
      the skin of one individual volunteer collected at different ages. Over a period
      of 27 years (donor age 36 years to 62 years), we obtained skin cells four times
      at appropriate intervals, and established eight fibroblast lines. These human
      fibroblasts have presented evidence for a correlation between donor age and
      proliferative lifespan in vitro. This result parallels the fact that telomeric
      DNA size cultured fibroblasts decrease with the increase in donor age. These cell
      lines had a normal diploid human chromosome constitution and will be useful in
      studies of human biology including aging.

PMID- 19385099
TI  - Hopscotch games in Denmark: a report on tradition and innovation with a brief
      look at other Scandinavian countries.

PMID- 19385100
TI  - Witchcraft trials in Uppland before the great northern Swedish witch trials of
      1668-1676.

PMID- 19385101
TI  - [Biology, medicine, and eugenics in Uruguay].

PMID- 19385102
TI  - [The influence of the Mexican Eugenics Society on education and social medicine].

PMID- 19385103
TI  - [The development of eugenics in Cuba].

PMID- 19385104
TI  - [Eugenicists, but with prudence].

PMID- 19385105
TI  - [Eugenics in Spain, between science and sociopolitical     doctrine].

PMID- 19385106
TI  - [Gregorio Maranon's eugenic thought].

PMID- 19385107
TI  - Requirements for submission of bioequivalence data; final rule. Final rule.
AB  - The Food and Drug Administration (FDA) is amending its regulations on the
      submission of bioequivalence data to require an abbreviated new drug application
      (ANDA) applicant to submit data from all bioequivalence (BE) studies the
      applicant conducts on a drug product formulation submitted for approval. In the
      past, ANDA applicants have submitted BE studies demonstrating that a generic
      product meets bioequivalence criteria in order for FDA to approve the ANDA, but
      have not typically submitted additional BE studies conducted on the same drug
      product formulation, such as studies that do not show that the product meets
      these criteria. FDA is amending the regulation because we now believe that data
      from additional BE studies may be important in our determination of whether the
      proposed formulation is bioequivalent to the reference listed drug (RLD), and are
      relevant to our evaluation of ANDAs in general. In addition, such data will
      increase our understanding of how changes in components, composition, and methods
      of manufacture may affect product formulation performance.

PMID- 19385108
TI  - Medicare program; changes to the competitive acquisition of certain durable
      medical equipment, prosthetics, orthotics and supplies (DMEPOS) by certain
      provisions of the Medicare Improvements for Patients and Providers Act of 2008
      (MIPPA). Interim final rule with comment period.
AB  - This interim final rule with comment period implements certain provisions of
      section 154 of the Medicare Improvements for Patients and Providers Act of 2008
      (MIPPA) related to the durable medical equipment, prosthetics, orthotics, and
      supplies (DMEPOS) Competitive Acquisition Program. Specifically, this rule:
      Implements certain MIPPA provisions that delay implementation of Round 1 of the
      program; requires CMS to conduct a second Round 1 competition (the "Round 1
      rebid") in 2009; and mandates certain changes for both the Round 1 rebid and
      subsequent rounds of the program, including a process for providing feedback to
      suppliers regarding missing financial documentation and requiring contractors to
      disclose to CMS information regarding subcontracting relationships.

PMID- 19385109
TI  - Medicare program: Medicare Advantage and prescription drug programs MIPPA drug
      formulary & protected classes policies. Interim final rule with comment period.
AB  - This interim final rule with comment period revises the regulations governing the
      Medicare prescription drug benefit program (Part D). This regulation makes
      conforming changes to reflect revisions to the rules governing Part D that were
      made as a result of provisions in the Medicare Improvements for Patients and
      Providers Act (MIPPA), which became law on July 15, 2008. These MIPPA provisions
      change the definition of a covered Part D drug, and add new requirements that
      apply to Part D formularies.

PMID- 19385110
TI  - Health insurance reform; modifications to the Health Insurance Portability and
      Accountability Act (HIPAA) electronic transaction standards. Final rule.
AB  - This final rule adopts updated versions of the standards for electronic
      transactions originally adopted under the Administrative Simplification subtitle
      of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). This
      final rule also adopts a transaction standard for Medicaid pharmacy subrogation.
      In addition, this final rule adopts two standards for billing retail pharmacy
      supplies and professional services, and clarifies who the "senders" and
      "receivers" are in the descriptions of certain transactions.

PMID- 19385111
TI  - HIPAA administrative simplification: modifications to medical data code set
      standards to adopt ID-10-CM and ICD-10-PCS. Final rule.
AB  - This final rule adopts modifications to two of the code set standards adopted in
      the Transactions and Code Sets final rule published in the Federal Register
      pursuant to certain provisions of the Administrative Simplification subtitle of
      the Health Insurance Portability and Accountability Act of 1996 (HIPAA).
      Specifically, this final rule modifies the standard medical data code sets
      (hereinafter "code sets") for coding diagnoses and inpatient hospital procedures
      by concurrently adopting the International Classification of Diseases, 10th
      Revision, Clinical Modification (ICD-10-CM) for diagnosis coding, including the
      Official ICD-10-CM Guidelines for Coding and Reporting, as maintained and
      distributed by the U.S. Department of Health and Human Services (HHS),
      hereinafter referred to as ICD-10-CM, and the International Classification of
      Diseases, 10th Revision, Procedure Coding System (ICD-10-PCS) for inpatient
      hospital procedure coding, including the Official ICD-10-PCS Guidelines for
      Coding and Reporting, as maintained and distributed by the HHS, hereinafter
      referred to as ICD-10-PCS. These new codes replace the International
      Classification of Diseases, 9th Revision, Clinical Modification, Volumes 1 and 2,
      including the Official ICD-9-CM Guidelines for Coding and Reporting, hereinafter
      referred to as ICD-9-CM Volumes 1 and 2, and the International Classification of
      Diseases, 9th Revision, Clinical Modification, Volume 3, including the Official
      ICD-9-CM Guidelines for Coding and Reporting, hereinafter referred to as ICD-9-CM
      Volume 3, for diagnosis and procedure codes, respectively.

PMID- 19385112
TI  - Medicaid program; premiums and cost sharing. Final rule; delay of effective data
      and reopening of comment period.
AB  - In accordance with the memorandum of January 20, 2009, from the Assistant to the
      President and Chief of Staff, entitled "Regulatory Review Plan," this action
      temporarily delays for 60 days the effective date of the final rule entitled
      "Medicaid Program; Premiums and Cost Sharing" (73 FR 71828). The temporary 60-day
      delay in effective date is necessary to give Department officials the opportunity
      for further review and consideration of new regulations. In addition, this action
      reopens the comment period on the policies set out in the November 25, 2008 final
      rule.

PMID- 19385113
TI  - ["Usines a guerir": from electroradiology to anticancer centers: technical change
      and administrative thought in the fight against cancer in France].

PMID- 19385114
TI  - [The Jordan will purify us: German Gamazo's educational reform     in 1898].

PMID- 19385115
TI  - [A "summa" of German Romantic natural philosophy: Lorenz Oken's "Lehrbuch der
      Naturphilosophie." Part 2].

PMID- 19385116
TI  - [The reception of the Mendelian chromosome theory in Spain:     the contribution
      of Jose Fernandez Nonidez].

PMID- 19385117
TI  - [The therapeutic use of mineral products in 16th-century Spain: the book of
      "Medicamentos Simples" by Juan Fragoso and Juan Calvo's "Antidotario"].

PMID- 19385119
TI  - [Experience of work of units of clinical neuropsychology in district neurological
      clinics of the Moscow outpatient service].

PMID- 19385118
TI  - To explant or not to explant: an invasive and noninvasive monitoring protocol to
      determine the need of continued ventricular assist device support.
AB  - Predictors of myocardial recovery after ventricular assist device (VAD)
      implantation are not well defined. The authors report their current VAD weaning
      protocol. Between 2003 and 2006, 38 patients received VAD implants. The authors
      performed 5 tests in 4 patients in whom echocardiography findings suggested
      myocardial recovery after implant. The protocol consists of assessing symptoms,
      electrocardiographic findings, hemodynamics, and cardiac function at baseline and
      as VAD support is weaned. As a result, 3 patients passed the weaning protocol and
      were explanted. There has been no recurrence of heart failure 667, 752, and 1007
      days after explant, respectively. One patient failed the protocol after 151 days
      of support because of low cardiac index during the protocol. This patient was
      transplanted. This current experience of VAD weaning protocol is a novel tool to
      identify candidates for successful VAD explantation.

PMID- 19385120
TI  - [Efficacy of dynamic magnetic therapy in the complex treatment of cognitive
      disturbances in patients with chronic cerebrovascular insufficiency].

PMID- 19385121
TI  - [Immunological reactivity in schizophrenic patients (antitoxic immunity to
      diphtheria)].

PMID- 19385122
TI  - [Correction of clinical presentations of the emotional burnout syndrome].

PMID- 19385123
TI  - [Risk factors of lateral amyotrophic sclerosis: a case-control study].

PMID- 19385124
TI  - [Pathogenetic and therapeutic aspects of dementia in Parkinson's disease].

PMID- 19385125
TI  - [Neurosyphilis].

PMID- 19385126
TI  - Bevacizumab in non-small cell lung cancer: new indication. Too many adverse
      effects to justify its use.
AB  - The numerous adverse effects (especially life-threatening infections and
      bleeding) outweigh the at best only moderate efficacy.

PMID- 19385127
TI  - [Standards of postmortem studies and services: a new normative basis of
      postmortem service].
AB  - Standards for organization of a postmortem service have been approved by the
      Russian Health Care Surveillance Committee in 2006.

PMID- 19385128
TI  - [Independent postmortem examination: contents of its concept, organizational
      aspects of its performance].
AB  - The paper discloses the contents of the concept of independent postmortem
      examination and describes the organizational aspects of postmortem examination
      according to the materials of primary postmortem studies of autopsy and biopsy of
      surgically removed organs.

PMID- 19385129
TI  - [Frequency of divergence of final clinical and anatomical diagnoses as an
      indicator of medical care quality].
AB  - The authors show it necessary to modify the frequency of divergence between final
      clinical and anatomical diagnoses as an indicator of health care. This parameter
      should be integral and based on the analysis of the leading principles of
      analysis of a revealed faulty of health care, by taking into account both
      controllability of the underlying disease at the moment of a patient's first
      visit to a doctor for its manifestations and at the stage of health care delivery
      when misdiagnosis and maltreatment are made.

PMID- 19385130
TI  - [Foreign experience in registering and analyzing the poor outcomes of treatment].
AB  - Negative consequences of treatment are observed at least in 16% patients at
      multidisciplinary hospitals and may result from the causes that are independent
      of medical staff, but more frequently from errors and inadequate treatment
      standards due to human factors. Systematic improvement of professionalism, which
      should be started from some educational reforms at medical institutes, is needed.

PMID- 19385131
TI  - [Cardiac valve diseases: morphological characteristics and differential
      diagnosis].
AB  - Macroscopic, organometric, histological, cytological, and immunohistochemical
      studies and polymerase chain reaction using a statistical analysis have revealed
      that the most informative morphological signs for the differential diagnosis of
      cardiac valve diseases were identified, by using the material involving 1326
      valves from the patients operated on and 221 hearts from patients who had died
      from cardiac defects, and 30 hearts from patients with coronary heart disease (a
      control group).

PMID- 19385132
TI  - [Clinical and morphological characteristics and factors of prognosis of pulmonary
      thromboembolism].
AB  - Analysis of 146,521 autopsy protocols in Moscow in 2001-2005 showed that the
      incidence pulmonary thromboembolism (PTE) as a direct cause of death was 3.8-7%.
      PTE was not diagnosed during life in 20-28% of the patients who had died at
      hospitals and in 68-72% of those who had died at home. PTE was 2-3 times more
      common in females than in males, the age of the deceased patients was old and
      senile. The sources of PTE were thrombi of the leg deep veins (93.2%), small
      pelvic veins (3.4%), and right heart chambers (1.1%). Thrombophilic states were
      one of the main causes of the poor course and outcome of PTE. Based on the
      studies performed, an algorithm was developed for the diagnosis and treatment,
      which was successfully used at the N.N. Burdenko Main Military Clinical Hospital.
      The introduction of the results could reduce the incidence venous thrombosis from
      39% to 17%, that of cava-filter thromboses from 24% to 3.7%, and recurrent TELA
      from 15% to 5.6%.

PMID- 19385133
TI  - [Analysis of fatal outcomes issues of typhus fever].
AB  - The nature and frequency of complications in patients with typhus fever are of
      importance for its outcome. The causes of death were studied in 126 patients who
      had died from this disease. The immediate causes of death were as follows:
      infectious-toxic shock (31.7%), pneumonia (28.6%), and perforative peritonitis
      (26.2%). The pathomorphism of Payer's patches does not allow the stages of the
      disease to be identified. An immunohistochemical study established a drastic
      preponderance of granulomatous macrophages without proliferation markers with a
      simultaneous reduction in the count of T and B lymphocytes and dendritic cells.

PMID- 19385134
TI  - [Embryonic hepatic sarcoma in children: aspects of morphological diagnosis].
AB  - 13 cases of embryonic undifferentiated sarcoma of the liver were examined. The
      tumor was detected in children: 50% being between 5-6 years of age and no sex
      domination was found. The tumors were solitary, large, well demarcated and had
      cystic areas of gelatinous degeneration. The tumor was composed of atypical
      round, stellate, spindle and epithelioid-like cells that were loosely arranged in
      a myxoid stroma. Entrapped bile ducts were commonly present. Electron microscopic
      and immunohistochemical findings showed no clear-cut differentiation of embryonic
      sarcoma cells.

PMID- 19385135
TI  - [Gastrointestinal stromal tumor of the esophagus].
AB  - The paper describes a rare case of a stromal tumor of the esophagus in a 68-year
      old male who was initially diagnosed as having esophageal leiomyoma after biopsy
      and study of a surgical material. Stromal tumour could be diagnosed by
      immunohistochemical (positive expression of oncomarkers; CD117, CD34, vimentin,
      CD99, and GFAP) and molecular genetic (real-time PCR) studies. This case confirms
      that it is necessary to use an immunohistochemical study in patients with spindle
      cell tumors of the gastrointestinal tract.

PMID- 19385136
TI  - [Epidemiology, novelty in the classification of renal cancer].
AB  - The data on morbidity and mortality due to renal cancer and the role of the major
      etiologic factors of the disease are presented. The frequency of different
      histological types, changes in the histological and TNM classifications,
      requirements for a pathohistological study and for evaluation of the stage of
      renal cell carcinoma are provided. Emphasis is laid on the necessity of
      developing a uniform standard for a pathohistological examination of renal
      neoplasms, by taking into account the WHO recommendations.

PMID- 19385137
TI  - [Glial tumors of the brain: current aspects of their classification and bases for
      genetic predisposition].
AB  - Gliomas are the most common tumors of the central nervous system (CNS). Malignant
      astrocytic gliomas account for 50% of all primary brain tumors. Cells of origin
      are unknown for the majority of brain tumors: CNS tumors have frequently in their
      content many histological forms and their classification will depend on what the
      parts of neoplasm that will be clearly identified at the material taking and
      further investigation. Current immunohistochemical studies may determine the
      antigenic structure of a tumor cell, compare it with the antigens expressed by a
      certain cell type and, thus, classify the tumor by its origin, but there are no
      antibodies which would correctly identify different types of tumors. The lecture
      reflects the current classifications of glial tumors: the typical three-leveled
      classification, the Kernokhan classification, the Duma-Duport classification. A
      part of the lecture deals with the specific features of genetics and molecular
      biology of gliomas: recent studies cast any doubt on the existing data on the
      sources of growth of these tumors.

PMID- 19385138
TI  - CLABSI in the crosshairs. New program targets infections in ICUs across the
      country. Interview by Alan Joch.

PMID- 19385139
TI  - Weathering the recession.

PMID- 19385140
TI  - Licensed to fill.

PMID- 19385141
TI  - Looking past the silver lining. Assess technology to help prevent hospital
      acquired conditions.

PMID- 19385142
TI  - Technology's role in infection prevention.

PMID- 19385143
TI  - Automated tools aid in infection control.

PMID- 19385144
TI  - Build quality leadership for a stronger department, organization.

PMID- 19385145
TI  - "Don't tell her she's on hospice": ethics and pastoral care for families who
      withhold medical information.
AB  - When family members enroll a patient in hospice, they sometimes request that the
      patient not be told of the diagnosis and their enrollment in hospice--usually so
      the patient won't be sad. In these situations, hospice staff face an ethical
      dilemma involving a patient's right to full disclosure. A discussion of this
      issue at an ethics committee session, chaired by the author of this article,
      brought to light many personal dynamics associated with these situations, and the
      discussion is used by the author to draw conclusions about pastoral care for
      these patients and families. Several responses from colleagues follow.

PMID- 19385146
TI  - Truth telling and openness create ethical tension: a response to Gentry.

PMID- 19385147
TI  - Telling the truth: Bonhoeffer revisited in response to Gentry's discussion.

PMID- 19385148
TI  - "First, cause no harm": a response to Gentry.

PMID- 19385149
TI  - Withholding information from patients: a response to Gentry.

PMID- 19385150
TI  - Out, damned spot! Out, I say!

PMID- 19385151
TI  - Canadian Association of Radiologists national advisory on gadolinium
      administration and nephrogenic systemic fibrosis.

PMID- 19385152
TI  - Magnetic resonance imaging of the urinary bladder: cancer staging and beyond.

PMID- 19385153
TI  - Complications after liver transplantation: evaluation with magnetic resonance
      imaging, magnetic resonance cholangiography, and 3-dimensional contrast-enhanced
      magnetic resonance angiography in a single session.
AB  - OBJECTIVE: To evaluate a comprehensive magnetic resonance imaging (MRI) protocol
      as noninvasive diagnostic modality for simultaneous detection of parenchymal,
      biliary, and vascular complications after liver transplantation. METHODS: Fifty
      two liver transplant recipients suspected to have parenchymal, biliary, and (or)
      vascular complications underwent our MRI protocol at 1.5T unit using a phased
      array coil. After preliminary acquisition of axial T1w and T2w sequences,
      magnetic resonance cholangiography (MRC) was performed through a breath-hold,
      thin- and thick-slab, single-shot T2w sequence in the coronal plane. Contrast
      enhanced magnetic resonance angiography (CEMRA) was obtained using a 3
      dimensional coronal spoiled gradient-echo sequence, which enabled acquisition of
      32 partitions 2.0 mm thick. A fixed dose of 20 ml gadobenate dimeglumine was
      administered at 2 mL/s. A post-contrast T1w sequence was also performed. Two
      observers in conference reviewed source images and 3-dimensional reconstructions
      to determine the presence of parenchymal, biliary, and vascular complications.
      MRI findings were correlated with surgery, endoscopic retrograde cholangiography
      (ERC), biopsy, digital subtraction angiography (DSA), and imaging follow-up.
      RESULTS: MRI revealed abnormal findings in 32 out of 52 patients (61%), including
      biliary complications (anastomotic and nonanastomotic strictures, and lithiasis)
      in 31, vascular disease (hepatic artery stenosis and thrombosis) in 9, and
      evidence of hepatic abscess and hematoma in 2. ERC confirmed findings of MRC in
      30 cases, but suggested disease underestimation in 2. DSA confirmed 7 magnetic
      resonance angiogram (MRA) findings, but suggested disease overestimation in 2.
      CONCLUSION: MRI combined with MRC and CEMRA can provide a comprehensive
      assessment of parenchymal, biliary, and vascular complications in most recipients
      of liver transplantation.

PMID- 19385154
TI  - Positive intraluminal bowel contrast on computed tomography following oral
      ingestion of kayexelate.
AB  - Our study presents the computed tomography (CT) manifestations of orally ingested
      kayexelate (a powdered form of sodium polystyrene sulphonate) used to treat
      hyperkalemia. Five patients with whom kayexalate appeared as high-attenuating
      intraluminal enteric content, similar to oral contrast material or leakage of
      intravascular contrast, are reported. Radiologists should be familiar with its
      appearance as it may mimic oral or vascular contrast within the gastrointestinal
      tract, a finding that may lead to a diagnostic error or misinterpretation.

PMID- 19385155
TI  - Case of the month #139. Central nervous system Langerhans cell histiocytosis.

PMID- 19385156
TI  - Case of the month #140. Isolated cortical vein thrombosis of left vein of Labbe.

PMID- 19385157
TI  - Case of the month #141. Rhombencephalosynapsis.

PMID- 19385159
TI  - "Cross" fused ectopia.

PMID- 19385158
TI  - Case of the month #142. Ruptured pelvic echinococcal cysts.

PMID- 19385160
TI  - Infusion reactions associated with monoclonal antibodies in patients with solid
      tumors. Introduction.

PMID- 19385161
TI  - Anaphylaxis: implications of monoclonal antibody use in oncology.
AB  - Anaphylaxis is currently classified as an immunologically triggered response with
      reactions that are IgE-mediated and reactions that are not IgE-mediated. This
      immunologically mediated phenomenon can result in various clinical
      manifestations, including decreased blood pressure, generalized skin
      inflammation, such as hives and pruritus, and respiratory symptoms, such as
      wheezing or bronchospasm. The severity of anaphylaxis can range from a mild
      allergic reaction to a potentially fatal anaphylactic shock. Numerous causative
      agents trigger anaphylactic reactions, and some of the best described include
      food and bee sting allergens. Monoclonal antibodies, which are increasingly used
      in the treatment of various malignancies, also can cause anaphylaxis. In this
      review, the mechanisms governing anaphylaxis along with treatment strategies are
      reviewed. Diagnostic aids for anaphylaxis are also discussed. Increased awareness
      of the mechanisms, symptoms, and treatment of anaphylaxis can aid caregivers to
      make informed decisions when new agents, such as monoclonal antibodies, are
      introduced into the clinic.

PMID- 19385162
TI  - Infusion reactions to monoclonal antibodies for solid tumors: immunologic
      mechanisms and risk factors.
AB  - The development of monoclonal antibodies targeting various receptors and ligands
      has been a significant advance in cancer therapy. These monoclonal antibodies are
      generally well tolerated. A subset of patients, however, experience infusion
      reactions with symptoms ranging from mild to life-threatening anaphylaxis. The
      underlying mechanisms of these reactions are not well characterized. In this
      review, current findings in clinical risk factor assessments and known mechanisms
      of these infusion reactions are discussed.

PMID- 19385163
TI  - Management of infusion reactions in clinical trials and beyond: the US and EU
      perspectives.
AB  - Monoclonal antibodies have expanded our cancer-fighting armamentarium in both the
      United States and Europe. While in general, monoclonal antibodies are well
      tolerated and do not have significant overlapping side effects with traditional
      cytotoxic agents, severe infusion reactions (IRs)--sometimes severe enough to be
      life threatening--have been reported. The pathophysiology of severe infusion
      reactions associated with monoclonal antibodies is poorly understood, but
      mechanisms are beginning to be elucidated. Geographic differences in the
      incidence of IRs have become apparent. Understanding the risk, recognizing the
      signs and symptoms, and being ready to promptly manage severe IRs are key for the
      clinician to avoid unnecessarily discontinuing these effective anticancer agents
      and prevent potentially tragic consequences for their patients. To date, clinical
      trials have incorporated monoclonal antibodies into combinations with standard
      cytotoxic regimens; it is expected that in time clinical trials will be testing
      promising new combinations utilizing multiple targeted agents, resulting in
      improved toxicity profiles and efficacy for cancer patients.

PMID- 19385164
TI  - Management of hypersensitivity reactions: a nursing perspective.
AB  - Infusion reactions occur commonly with the administration of monoclonal antibody
      therapy and can vary in severity. Oncology nurses have experience in
      hypersensitivity reactions with different chemotherapy agents, but with the
      increased use of monoclonal antibody therapy in the treatment of various cancers,
      knowledge of specific risk and management of reactions with these therapies is
      important. Anaphylactic reactions are mediated by IgE and anaphylactoid reactions
      are not; monoclonal antibody reactions are also considered to be associated with
      cytokine release syndrome, which has a specific constellation of symptoms
      associated with it. Infusion reactions, while common, have the potential to be
      distressing and frightening to oncology nurses. These challenging occurrences
      also can increase hospitalization costs. Strategies to manage reactions have
      included patient desensitization, alteration of infusion rates, skin testing, and
      the use of premedication. Baseline comprehensive assessments, including allergy
      history, are important in reducing or preventing hypersensitivity reactions.
      Clinical pathways or established guidelines can help to familiarize staff with
      appropriate responses to infusion reactions and nurses should be aware of the
      variety of symptoms which can indicate infusion or hypersensitivity reactions.
      Oncology nurses should understand the management of hypersensitivity and
      anaphylaxis; the Oncology Nursing Society and the American Heart Association have
      both published guidelines to assist practicing health-care professionals with the
      management of this potentially fatal adverse event. Knowledge of emergency drugs
      and mechanism of action is vital. Nurses should be aware of appropriate emergency
      response as well as management of delayed or biphasic hypersensitivity reactions.
      Oncology nurses should be well-prepared for these often common events.

PMID- 19385165
TI  - Health economic analysis of the burden of infusion reactions on patients,
      caregivers, and providers.
AB  - The cost and efficiency of medical care is an ongoing issue that has a particular
      effect on patients and caregivers within the community oncology setting.
      Monoclonal antibody (MoAb) therapy has proven to be effective in the treatment of
      cancer patients. Although MoAbs are associated with minimal toxicity, they can
      cause infusion reactions (IRs) in some patients. Managing these infusion
      reactions leads to an increased burden on patients, caregivers, and providers.
      Health economic models can quantify the burden that MoAb-induced IRs have on the
      patient and can help identify ways to maximize the efficiency of providing
      quality health care. This review identifies the specific burden, including tasks
      and associated costs, that IRs have on the patient and caregivers, and discusses
      the importance of using this information to help manage IRs. Nurses are often the
      first to respond when an IR occurs and the particular impact IRs have on nurses
      is reviewed. Patients, caregivers, and providers should be aware of the potential
      burden that MoAb-induced IRs can have on a patient and use this information to
      help guide clinical decisions.

PMID- 19385166
TI  - [Some key issues about scientific research on traditional Chinese medicine].
AB  - Since the Tenth Five-Year Plan in China, the science and technology of
      traditional Chinese medicine (TCM) has gained unprecedented high attention, and
      at the same time, the people who have been engaging in the TCM research are
      bearing more and more missions and responsibilities. In order to get more
      significant breakthroughs and scientific achievements with great innovation,
      great value and great influence in the near future, the radical target and
      strategy for TCM research should be made out as follows: sifting out the lees,
      laying aside the disputes, tamping the identical opinions, and innovating to
      apply. In other words, the principle that "to do what can be done, not to do what
      can not be done; to do what should be done, not to do what should not be done,
      and to pay more attention to standardization than to innovation" should be
      recognized unequivocally. The six issues such as the evaluation and improvement
      of TCM efficacy, the safety evaluation and reasonable usage of TCM, the
      innovation and development of TCM quality evaluation and control technology, the
      sustainable utilization and protection of TCM resources, the elucidation and
      modernization of TCM basic theory, etc. should be considered as the prior and key
      aspects of TCM research in the following 20 years in China.

PMID- 19385167
TI  - [Reproductive biology of Dendrobium officinale (Orchidaceae) in Danxia landform].
AB  - OBJECTIVE: To reveal the breeding system and endangered mechanism of Dendrobium
      officinale in Danxia landform. METHOD: The habitat, growth traits, floral
      phenology, propagation characteristic and status of resource destruction of D.
      officinale in Danxia landform were investigated. RESULT: The results showed that
      D. officinale grew in poor condition and the growth summit appeared in spring;
      its two- or three-years-old stems could be bloomed; higher seed-setting rate
      would be obtained when pollinated in time; the ovary began swelling after
      pollinated four or five days, until about 185 days later, the fruit matured; the
      seed-setting rate was very low (0.31%) in natural environment; only one clone was
      generated from one stem in a clump in annual. CONCLUSION: D. officinale mainly
      reproduces by clonal propagation; over-collection is key factor which leads D.
      officinale to be in endangered status at present in this region.

PMID- 19385168
TI  - [Analysis of catharanthine content and agronomic traits in Catharanthus roseus].
AB  - Catharanthine content and agronomic traits in major Catharanthus roseus varieties
      were analyzed. It was found that there existed great difference in catharanthine
      content and agronomic traits among the varieties. Catharanthine content was the
      highest in variety Pacifica Polka Dot (PPD), reaching 3.79 mg g(-1) dry leaf
      weight, and the lowest in variety Cooler Pink (CP) with only 0.9 mg g(-1) dry
      leaf weight. Correlation existed in certain extent between catharanthine content
      and agronomic traits in C. roseus. Path analysis showed that among all the
      agronomic traits analyzed, internodal distance positively affected catharanthine
      content at significant level (P<0.05), with the path coefficient being 1.473.
      This study provides useful information for high-catharanthine content C. roseus
      introduction and breeding.

PMID- 19385169
TI  - [Effects of water stress in spring on membrane lipid peroxidation in in leaves of
      Ligusticum chuanxiong].
AB  - OBJECTIVE: To study the effects of continuous dry-stress and full-water
      treatments in different periods of spring on the water condition, permeability of
      plasma membrane and protective enzymes activities in leaves of Ligusticum
      chuanxiong. METHOD: Pot cultivation method was applied and physical and
      biochemical indexes were measured. RESULT: Under dry-stress treatment the soil
      relative water content (SRWC) and the relative water content (RWC) in leaves
      decreased gradually with the days of treatment increased, the content of
      malondialdephyde (MDA) and permeability of plasma membrane increased
      significantly. The activities of superoxide dismutase (SOD) and catalase (CAT)
      increased at first and then decreased while the activity of peroxidase (POD)
      increased. The influence of full-water treatment to all above indexes was the
      same trend with that of dry-stress treatment approximately but was not
      significant. CONCLUSION: In this experiment, the suitable soil relative water
      content for growth of Chuanxiong is about 60%.

PMID- 19385170
TI  - [Analysis of genetic difference among Scrophularia ningpoensis cultivars by
      SRAP].
AB  - OBJECTIVE: The genetic difference among Scrophularia ningpoensis cultivars were
      analyzed in molecular level. METHOD: Ninety-two individuls of three S.
      ningpoensis cultivars were employed to be analyzed by the approach of Sequence
      related Amplified Polymorphism (SRAP).The parameters were calculated by
      POPGENE1.31 and the relationship was constructed based on UPGMA method. RESULT:
      1) A total of 227 bands were scored and 199 bands of them were polymorphic. 2)
      The result is showed that there is a medium level of genetic diversity among
      three cultivars. At species level: percentage of polymorphic loci PPB=52.42%,
      effective number of alleles N(e)=1.2812, Nei's gene diversity H=0.1671 and
      Shannon's information index H(sp)= 0.2526; At cultivar level: PPB=21.44%,
      N(e)=1.1216, Nei's gene diversity H=0.0725 and Shannon's information index
      H(pop)= 0.1083. 3) The Nei's coefficient of genetic differentiation was 0.5625,
      which was consistent with the Shannon's coefficient of genetic differentiation
      (0.5713). Most of the genetic variation existed among cultivars. 4) The gene flow
      (N(m)=0.3889) was less among cultivars, indicating that the degree of genetic
      differentiation was higher. 5) Genetic similarity coefficient were changed from
      0.8082 to 0.9133. By clustering analysis, the classified result of SRAP marker
      between traditional modal character was almost same. CONCLUSION: The genetic
      diversity of samples of S. ningpoensis is medium. The genetic difference among
      cultivar is higher than that within cultivar.

PMID- 19385171
TI  - [Evaluation on in vitro release of Chinese medicinal compound sustained release
      preparations using multi-index chromatographic fingerprint].
AB  - OBJECTIVE: To establish a method to evaluate the in vitro release of Chinese
      medicinal compound sustained release preparations using multi-index
      chromatographic fingerprint. METHOD: With the Chinese medicinal compound Jiangya
      sustained tablets as model preparation, the in vitro cumulative release of the
      main component flavones and fingerprint were determined by HPLC fingerprint.
      Aacacetin, rutin, luteolin, fingerprint were determined simultaneously and used
      to calculate the in vitro cumulative release of the tablets. RESULT: Aacacetin,
      rutin, luteolin, and the fingerprint had different cumulative release.
      CONCLUSION: Multi-index chromatographic fingerprint can reflect different content
      of multi components of preparations and can be used in the evaluation on in vitro
      release of the sustained release preparations of Chinese medicinal compound. The
      method is simple, rapid, and of multi information.

PMID- 19385172
TI  - [Preparation of nanostructured lipid carriers loaded with supercritical carbon
      dioxide fluid extraction of Xionggui powder].
AB  - OBJECTIVE: To study the preparation ofnanostructured lipid carriers loaded with
      supercritical carbon dioxide fluid extraction of Xionggui powder. METHOD:
      Prepared nanostructured lipid carriers (NLC) loaded with supercritical carbon
      dioxide fluid extraction of Xionggui powder (XG-CO2-SFE) with a microemulsion
      ultrasonication method , established the best prescription of XG-CO2-SFE-NLC by
      orthogonal design methods with entrapment efficiency of nanoparticles as index,
      and investigated their physicochemical characterizations. RESULT: The best
      prescription was m(phospholipid) : m(S-40) : m(lipid carriers) = 5 : 2 : 1, the
      entrapment efficiency of nanopartices was 86.8%, results revealed that
      nanoparticles were sphere like with the mean size of 92.6 nm and the mean zeta
      potential was -20.68 mV. CONCLUSION: The prep aration method of the XG-CO2-SFE
      NLC is appropriate.

PMID- 19385173
TI  - [Application of fuzzy mathematics on modifying taste of oral solution of
      traditional Chinese drug].
AB  - OBJECTIVE: To apply Fuzzy mathematical methods to choose the best taste modifying
      prescription of oral solution of traditional Chinese drug. METHOD: Jin-Fukang
      oral solution was used as a model drug. The oral solution was prepared in
      different taste modifying prescriptions, whose tastes were evaluated by the fuzzy
      quality synthetic evaluation system. RESULT: Compound-sweeteners with Sucralose
      and Erythritol was the best choice. CONCLUSION: Fuzzy integrated evaluation can
      be used to evaluate the taste of traditional Chinese medicinal pharmaceuticals,
      which overcame the artificial factors and achieve more objective conclusion.

PMID- 19385174
TI  - [Role of Radix Platycodi in Tianwang buxinwan decoction analyzed by
      fingerprints].
AB  - OBJECTIVE: To establish the fingerprints of the active fractions from Tian-wang
      bu-xin-wan decoction by HPLC, and to explain the role of Radix Platycodi in the
      decoction prescription. METHOD: The experimental conditions of the HPLC method
      were established as follows: Hanbon Lichrospher C18 column (4.6 mm x 250 mm, 5
      microm), mobile phase were methanol and 0.012 5 mol L(-1) ammonium acetate/acetic
      acid buffer, eluted with a linear gradient, flow rate was 1.0 mL min(-1), the
      photodiode array detector (PDA) and evaporative light scattering detector (ELSD)
      were connected in series. RESULT: In the same conditions and used same method,
      the extract amount of whole prescription was higher than that of excepting Radix
      Platycodi. The method provided two kinds of fingerprints with satisfied
      separation, which were the HPLC-PDA (Max Plot) fingerprint and the HPLC-ELSD
      fingerprint. And, they had good correlation and complementaritiy. CONCLUSION: The
      Radix Platycodi can enhance the decoction yield of the prescription; and increase
      the dissolution and the contents of some ingredients in the decoction.

PMID- 19385175
TI  - [Studies on extraction of Ligusticum chuanxiong in Hongye Xintong soft capsule by
      super critical fluid extraction].
AB  - OBJECTIVE: To study the rationality of extraction prosess for the Ligusticum
      chuanxiong in Hongye Xintong Soft Capsule by super critical fluid
      extraction(SFE). METHOD: Conditions for the extraction were optimized by
      orthogonal experimental design as guided by the extraction rate and content of
      ligustilid in the extract; Combined with the experiment of rats ligated the left
      coronary artery, the two compounds containing different extracts (steam
      distillation and SFE) were compared to determine the extraction prosess. RESULT:
      The best extraction conditions were established as following: pressure 30 MPa,
      temperature 50 degrees C, extracting time 4 h, separate pressure 10 MPa. separate
      temperature 40 degrees C. Compared with steam distillation, the compound
      containing SFE extract showed stronger protective effects on rats ligated the
      left coronary artery. CONCLUSION: Super critical fluid can extract active
      ingredients in Ligusticum chuanxiong effectively.

PMID- 19385176
TI  - [Studies on application of ultra-filtration to purifying polysaccharides from
      Rhubarb].
AB  - OBJECTIVE: To purify Rhubarb polysaccharides via micro-filtration and ultra
      filtration. METHOD: The technology adopted micro-filtration and tubular membrane
      with different cut-off molecular weights. RESULT: Experiment results showed that
      the optimum operating conditions were that the ultra-filtration time controlled
      around 80 min, the temperature was set the 35-40 degrees C, the operating
      pressure was 0.08-0.12 MPa, the pH was 6-8, and a sample that of polysaccharide
      was 0.5 times of original concentration. The recovery ratio of the
      polysaccharides was 53.7%, the concentration could be condensed to 2.73 times
      compared with the sample liquid. CONCLUSION: The technology was simple and
      feasible, it can be applied to purify Rhubarb polysaccharides.

PMID- 19385177
TI  - [Studies on chemical constituents of aerial roots of Ficus microcarpa].
AB  - OBJECTIVE: To investigate the chemical constituents of the aerial roots of Ficus
      microcarpa. METHOD: The solvent extraction and silica gel and Sephadex LH-20
      column chromatography were used to isolate and purify the constituents. The
      chemical structures were elucidated by physicochemical properties and the
      analysis of spectroscopic data. RESULT: Eight compounds were obtained and
      identified as (2S, 3S, 4R) -2-[(2'R) -2' - hydroxypentracosanoylamino]-
      heptadecane -1, 3, 4-triol (1), 12, 20 (30) -ursa-dien-3alpha-ol (2),
      epifriedelanol (3), alpha-amyrin acetate (4), beta-sitosterol (5), beta
      daucosterol (6), hexacosanoic acid (7), heneicosanoic acid (8), respectively.
      CONCLUSION: Compound 1 was a new compound and named as microcarpaceramide A.
      Compound 2 was isolated from the aerial roots of F. microcarpa for the first
      time.

PMID- 19385178
TI  - [Flavonoid constituents from herbs of Sarcopyramis bodinieri var. delicata].
AB  - Phytochemical studies of the the herb Sarcopyramis bodinieri var. delicate
      (Melastomataceae) have been carried out. The compounds were separated by repeated
      D101 macroporous adsorption resin column combined with Sephadex LH-20, ODS, and
      silica gel chromatgrophy. The structures were identified on the basis of
      extensive spectroscopic data analysis, and by comparison of their spectral data
      with those reported. Eight flavonoid compounds isolated from the ethyl acetate
      extract was identified as isorhamnetin (1), quercetin (2), isorhamnetin-3-O-beta
      D-glucopyranoside (3), quercetin-3-O-beta-D-glucopyranoside (4), isorhamnetin-3-O
      (6"-acetyl)-beta-D-glucopyranoside (5), isorhamnetin-3-O-(2"-acetyl)-beta-D
      glucopyranoside (6), quercetin-3-O-(6"-acetyl)-beta-D-glucopyranoside (7), and
      quercetin- 3-O-(6"-O-E-p-coumaroyl)-beta-D-glucopyranoside (8). All of the
      compounds were separated from the genus of Sarcopyramis for the first time.

PMID- 19385179
TI  - [Studies on chemical constituents from EtOAc fraction of Sorbus tianschanica].
AB  - OBJECTIVE: To study the chemical constituents of Sorbus tianschanica. METHOD: The
      compounds were isolated and purified by recrystallization and chromatography with
      silica gel and resin. Their structures were identified by physicochemical
      properties and spectral analysis. RESULT: Seven compounds were isolated from the
      EtOH extraction and six structures were identified as benzoic acid (1), benzyl-O
      beta-D-glucopyranoside (2), ursolic acid (3), 2alpha-hydroxyursolic acid (4),
      hyperoside (5), quercetin-3-O-glucoside (6). CONCLUSION: Compounds 1-5 were
      isolated from S. tianschanica for the first time.

PMID- 19385180
TI  - [Studies on chemical constituents of Evodia rutaecarpa].
AB  - OBJECTIVE: To study the constituents of Evodia rutaecarpa. METHOD: The
      constituents were isolated by various chromatographic techniques and the
      structures were elucidated by their physicochemical properties and the spectral
      data analysis. RESULT: Eleven compounds were isolated and identified as
      rutaecarpine (1), dehydroevodiamine (2), limonin (3), wuchuyuamide I (4),
      evocarpine (5), daucosterol (6), taraxerone (7), 14-ursen-3-ol-1-one (8), trans
      caffeic acid methylate (9), methyl coumarate (10), caffeine (11). CONCLUSION:
      Compounds 7, 8, 10, 11 were isolated from E. rutaecarpa for the first time.

PMID- 19385181
TI  - [Studies on chemical constituents from rhizomes of Hedychium chrysoleucum].
AB  - OBJECTIVE: To investigate the chemical constituents from the rhizome o fHedychium
      chrysoleucum. METHOD: The compounds were isolated by column chromatography on
      silica gel. The structures were identified by NMR, IR and MS analyses. RESULT:
      Seven compounds were isolated and identified as hedychenone (1), coronarin A (2),
      yunnancoronarin A (3), coronarin E (4), beta-sitosterol (5), cryptomeridiol (6),
      and beta-eudesmol (7). CONCLUSION: Compounds 1-7 were obtained from this plant
      for the first time.

PMID- 19385182
TI  - [Studies on chemical constituents from roots of Polygonum amplexicaule].
AB  - OBJECTIVE: To investigate the chemical constituents in the roots of Polygonum
      amplexicaule var. sinense. METHOD: The compounds were isolated by column
      chromatography on silica gel and Sephadex LH-20. The structures were identified
      by means of IR, 1H-NMR, 13C-NMR and MS analyses. RESULT: Eight compounds were
      isolated and identified as friedelin (1), beta-sitosterol (2), simiarenone (3),
      angelicin (4), psoralen (5), palmitic acid (6), (-)-epicatechin (7), and
      quercetin (8), respectively. CONCLUSION: All compounds were isolated from this
      species for the first time and compounds 1, 3-6 were obtained from this genus for
      the first time.

PMID- 19385183
TI  - [Study on C21 steroidal glycosides of Cynanchum atratum by LC-MS].
AB  - High performance liquid chromatography coupled with on-line electrospray tandem
      mass spectrometry (HPLC/ESI-MS/MS) was used to identify C21 steroidal glycosides
      in the roots of Cynanchum atratum. The structures of C21 steroidal glycosides
      were deduced from mass fragments features in positive and negative mode. The
      constituents of C. atratum were separated and detected. 7 compounds were
      identified by comparing their ESI-MS/MS data with the reference compounds and 2
      compounds were inferred solely by the ESI-MS/MS data. The method is sensitive,
      and provides good separation and rapid qualitative characterization of C21
      steroidal glycosides in the roots of C. atratum.

PMID- 19385184
TI  - [Determination of salylic acid, syringic acid, benzoic acid and anthranilic acid
      in Radix Isatidis by HPCE].
AB  - OBJECTIVE: To develop a simple and rapid capillary electrophoresis (CE) method
      for the separation and determination of four active organic acids including
      salicylic acid, syringic acid, benzoic acid, and anthranilic acid in Radix
      Isatidis. METHOD: The HPCE system consisted of a fused-silica capillary column of
      47.3 cm (38.3 cm to the detector) x50 microm i.d. and a mixture ofacetonitrile
      borate buffer (15% acetonitrile, 25 mmol L(-1) borate, 15 mmol L(-1) beta-CD, pH
      9.10) solution as the operating buffer. The applied voltage was 11.5 kV and the
      UV detection was set at 220 nm. The effects of the applied voltage, detection
      wavelength, and the pH of buffer, the concentration of buffer, acetonitrile and
      beta-CD were investigated. RESULT: The linear calibration rang was 3.0-90 mg L(
      1) (r=0.9994) for salylic acid, 4.0-120 mg L(-1) (r=0.9995) for syringic acid,
      2.0-60 mg L(-1) (r=0.9998) for benzoic acid and 5.0-100 mg L(-1) (r=0.9992) for
      anthranilic acid. The recoveries of salylic acid, syringic acid, benzoic acid and
      anthranilic acid were 95.9%-102.6%, 98.6%-103.4%, 98.7%-104.1%, 96.1%-104.3%
      respectively. The detection limits of salylic acid, syringic acid, benzoic acid
      and anthranilic acid were 0.7, 1.1, 1.2 and 1.5 mg L(-1), respectively.

PMID- 19385185
TI  - [Effect of Astragalus mongholicus on expression of transforming growth factor-
      beta1 in SD rats with unilateral ureteral occlusion].
AB  - OBJECTIVE: To study the effect of Astragalus mongholicus (AM) on the expression
      of transforming growth factor-beta1 (TGF-beta1) in SD rats with unilateral
      ureteral occlusion (UUO) and to elucidate the mechanisms underlying the
      renoprotective effects of AM. METHOD: Fifty-four Sprague-Dawley rats were
      randomly divided into 4 groups: sham-operation group, the UUO group and AM
      treatment group. After administration of AM (10 g kg(-1) d(-1)) for 3, 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 expression of TGF
      beta1 and alpha-smooth muscle actin (alpha-SMA) was measured by
      immunohistochemistry staining sections. The mRNA of TGF-beta1 and alpha-SMA were
      reverse transcribed and quantified by real-time PCR. The expression of TGF-beta1
      protein were assessed by Western blot. RESULT: Renal damage was exacerbated and
      the expression of alpha-SMA and TGF-beta1 were all significantly increased in UUO
      group compared with those of sham-operation group (P<0.05) at each time point.
      Tubular impairment and interstitial fibrosis were alleviated, and up-regulations
      of expressions of TGF-beta1 and alpha-SMA were significantly suppressed by AM
      treatment (P<0.05). CONCLUSION: AM can ameliorate renal interstitial fibrosis
      induced by UUO in vivo. The mechanisms of its antifibrotic effects might be
      related with the down-regulation of TGF-beta1 expression and suppression of
      tubular epithelial myofibroblast transdifferentiation in the progress of renal
      interstitial fibrosis.

PMID- 19385186
TI  - [Protective effects of AST and ASI on memory impairment and its mechanism in
      senescent rats treated by GC].
AB  - OBJECTIVE: To study the protective effects and mechanisms of astragaloside (AST)
      and astragalus saponin I (ASI) on the memory impairment in senescent rats treated
      by glucocorticoid (GC). METHOD: Y maze test was performed to determine the
      effects of AST and ASI on memory impairment of hydrocortisone(HC)-induced
      senescent rats. Using Ca2+ sensitive fluorescent indicator (Furo-2), free
      intracellular calcium concentration ([Ca2+]i) was measured by double wavelength
      fluorescence sepectrophotometer in thymocytes and hippocampal neurons induced
      dexamethasone (DEX). And apoptosis was detected by DNA gel electrophoresis and
      flow cytometry. RESULT: Compared with HC control, AST and ASI can improve the
      memory of the senescent rats treated by HC, lower [Ca2+]i and suppress apoptosis
      of thymocytes and hippocampal neurons induced by DEX. CONCLUSION: AST and ASI can
      delay the aging in rats treated by HC, and its mechanism may includ
      lowering[Ca2+]i and suppressing the apoptosis of thymocytes and hippocampal
      neurons.

PMID- 19385187
TI  - [Effects of artemether and dihydroarteannuin on mouse model of scleroderma].
AB  - OBJECTIVE: To study the effects of artemether and dihydroarteannuin on the mouse
      model of scleroderma. METHOD: Sixty mice were randomly divided into 8 groups: PBS
      control group, model group, menstruum group (20% Tween-80, 0.4%CMC-Na), positive
      medicine group (penicillamine 200 mg kg(-1)), low-dose artemether group (5 mg kg(
      1)), high-dose artemether group (20 mg kg(-1)), low-dose dihydroarteannuin group
      (5 mg kg(-1)), high-dose dihydroarteannuin group (25 mg kg(-1)). We have
      established a mouse model for scleroderma in Balb/c mice by subcutaneous
      injections of bleomycin 0.1 mL per day (200 mg L(-1) BLM) for 3 weeks. Meanwhile,
      the administration lasted for 4 weeks. The back skin was removed in the next day
      after the final administration. Treated skins and lungs were harvested and
      analyzed for histological sclerosis. The thickness of the skin and fibrosis
      degree of derma were observed and made an analysis of the contents of collagen
      and hydroxyproline. RESULT: Compared with the model groups, the high-dose groups
      markedly inhibited the thickness of derma (P<0.001), furthermore, the contents of
      collagen and hydroxyproline in the skin were also significantly reduced (P<0.05).
      Other groups of mice showed improvement on scleroderma. CONCLUSION: Our results
      suggest that administration of artemether or dihydroarteannuin may be an
      effective approach in preventing systemic sclerosis.

PMID- 19385188
TI  - [Effects of Dengzhan Xixin on blood-brain barrier permeability and metabolites
      after cerebral ischemia-reperfusion injuries].
AB  - OBJECTIVE: The investigated the effects of Dengzhan Xixin on brain water content,
      blood-brain barrier (BBB) permeability, T2-weighted imaging (T2WI), metabolites
      and the lesion ratio after cerebral ischemia-reperfusion injuries (IRI). METHOD:
      The 65 rats were randomly individed into three groups, the sham-operated group,
      the ischemia-reperfusion group and the Dengzhan Xixin treatment group. The models
      of ischemia-reperfusion of middle cerebral artery in rats were established by
      placing an intraluminal suture. The Dengzhan Xixin treatment group were injected
      10% Dengzhan Xixin injection 22.5 mg kg(-1) after ischemia 1.5 h. The sh am
      operated group (n=5) were sacrificed on 1 to measure brain water content and BBB
      permeability. The rats of the ischemia-reperfusion group (n=30) and the Dengzhan
      Xixin treatment group (n=30) were sacrificed at reperfusion for 6 h, 12 h, 1 d, 2
      d, 4 d, 7 d, respectively, after ischemia 1.5 h. The additional 35 rats were
      individed into the same three groups. The changes of T2WI and metabolites in the
      brain were observed, and rats were sacrificed at reperfusion for 1 d, 2 d, 4 d
      after ischemia 1.5 h to determine the lesion ratio by TTC. RESULT: In the
      ischemia-reperfusion group, brain water content(77.93+/-0.68)% and BBB
      permeability (3.77+/-0.28) increased after reperfusion for 6 h. The peak time of
      brain water content was at 4 d (83.82+/-0.49)% and BBB permeability was at 2 d
      (5.51+/-0.24)%. In the ischemia-reperfusion group and the Dengzhan Xixin
      treatment group, there were hyperintense signals in the injury region of T2WI. In
      the ischemia-reperfusion group after reperfusion for 1 d, the ratio of NAA/Cr
      decreased and Cho/Cr increased. In the Dengzhan Xixin treatment group, the ratio
      of NAA/Cr increased and Cho/Cr decreased. In the treatment group, the lesion
      ratio decreased by TTC was 16.78+/-1.45 and in the ischemia-reperfusion group was
      21.27+/-1.73 at 2 d. CONCLUSION: Dengzhan Xixin may relieve cerebral ischemia
      reperfusion injury by influencing the metabolites of brain, stabilizing BBB and
      decreasing brain edema.

PMID- 19385189
TI  - [Dynamic study on effect of Chinese medicine compound Yiliuyin on angiogenesis in
      transplanted S180 tumor of mouse].
AB  - OBJECTIVE: To investigate the dynamic changes in angiogenesis within the tumor
      tissue of mice bearing S180 tumor at different day-points of oral administration
      with a Chinese medicine compound "Yiliuyin" (YLY) and to explore the anti-tumor
      mechanisms of YLY in vivo. METHOD: Fifty-six BALB/c mice were divided into YLY
      group and control group (28 mice/group) and each group was divided into four
      subgroups (7 mice/subgroup), randomly. After 24 hrs of inoculation with S180
      tumor cells subcutaneously in the right axilla, YLY in the mice of YLY group and
      equal volume of cold boiled-water in the mice of control group were administered
      orally twice every day, 0.5 mL each time. The mice of one subgroup from the two
      groups apiece were killed at 10, 20, 30 th and 40 th day-point of oral
      administration, respectively. The tumors were isolated and were made into
      paraffin embedded sections. The dynamic changes of the angiogenesis (CD34
      staining), vascular endothelial growth factor (VEGF), vascular endothelial growth
      factor receptor-2 (VEGFR-2) and endostatin (ES) in tumor tissue were detected by
      immunohistochemistry staining, and the results were shown as PED (positive enzyme
      dot). RESULT: YLY could remarkably decrease the angiogenesis within tumor
      tissues. The PED of CD34 in control group at 10, 20, 30 th and 40 th day-point
      was 392.86+/-42.01, 481.49+/-58.34, 386.31+/-54.91 and 376.69+/-28.71, and that
      in YLY group was 334.46+/-33.38, 289.34+/-39.63, 257.09+/-40.00 and 246.57+/
      36.78, respectively. The PED of CD34 in YLY group at each day-point was lower
      than that in control group (P<0.05, P<0.01, P<0.01 and P<0.01, respectively). The
      PED of VEGF in control group at 10, 20, 30 th and 40 th day-point was 852.63+/
      81.65, 1168.40+/-96.69, 1292.60+/-147.54 and 1124.74+/-139.64, and that inYLY
      group was 718.40+/-94.94, 866.54+/-72.40, 859.31+/-74.02 and 753.34+/-72.95,
      respectively. The PED of VEGF in YLY group at each day-point was lower than that
      in control group (P <0.05, P <0.01, P <0.01 and P <0.01, respectively). The PED
      of VEGFR-2 in control group at 10th, 20th, 30th and 40th day-point was 618.63+/
      59.08, 750.09+/-56.72, 684.91+/-72.86 and 644.06+/-60.25, and that in YLY group
      was 523.91+/-64.66, 449.03+/-46.85, 400.06+/-60.12 and 339.89+/-45.39,
      respectively. The PED of VEGFR-2 in YLY group at each day-point was lower than
      that in control group (P <0.05, P <0.01, P <0.01 and P <0.01, respectively). The
      PED of ES in control group at 10th, 20th, 30th and 40th day-point was 250.26+/
      36.27, 298.60+/-44.41, 450.86+/-38.95 and 398.43+/-34.19, and that in YLY group
      was 249.57+/-40.23, 350.03+/-40.92, 499.40+/-40.29 and 497.94+/-42.76,
      respectively. There was no difference between the two groups at 10th day
      point.The PED of ES in YLY group was higher than that in control group at 20, 30,
      40 th day-point (P <0.05, P <0.01 and P <0.01, respectively) . CONCLUSION: YLY
      could exert the anti- tumor role by down-regulating the expression of VEGF and
      VEGFR-2, up-regulating the expression of ES and inhibiting the angiogenesis
      within tumor tissue.

PMID- 19385190
TI  - [Effect of Tianwang Buxin decoction or Tianwang Buxin without Radix platycodi
      decoction on brain neurotransmitter of rats hyposomnia model].
AB  - OBJECTIVE: To understand the action mechanism of Tianwang Buxin decoction that is
      the whole prescription included all drugs from Tianwang Buxin honeyed pill and
      Tianwang Buxin without radix platycodi decoction on the nerves-calming and
      hyposomnia-curing. METHOD: The influence of Tianwang Buxin decoction and Tianwang
      Buxin without radix platycodi decoction on somnus utilizing the mice' s somnus in
      coordination with Pentobarbital sodium was observed. Investigation whether the
      compatibility of radix platycodi affect the concentration of brain
      neurotransmitter, 5-HT, NA and DA, correlated sleep-awareness by HPLC-ECD
      detection was carried out after rats' hyposomnia model were founded. RESULT: The
      falling asleep rates of mice given subthreshold dose raised (P<0.05), remarkably
      because of Tianwang Buxin decoction. But there is significant difference with
      Tianwang Buxin lack of radix platycodi decoction despite the heightening
      tendency. All groups were discovered that the level of 5-HT and 5-HIAA, the
      monoamine transmitter, heighten obviously after the whole prescription and the
      prescription without radix platycodi were administered in nuclei raphae medullae
      oblongatae (P<0.05), but it is only the whole prescription group that emerged
      same phenomenon in the Ammon's horn and striatum area. Furthermore significant
      difference exist as comparing Tianwang Buxin whole prescription decoction with
      Tianwang Buxin without radix platycodi decoction. The level of another monoamine
      transmitter DA stepped up notably in the whole prescription and the prescription
      without radix platycodi groups following administration in corpora striata
      (P<0.05). CONCLUSION: The mechanism of hypnosis action lie in enhancement of
      releasing 5-HT in encephalic regions for the Tianwang Buxin whole prescription
      decoction, but it's possible that radix platycodi may be the key point that
      adjusts the additional quantity.

PMID- 19385191
TI  - [Effect of hawthorn flavanone on blood-fat and expression of lipogenesis and
      lipolysis genes of hyperlipidemia model mouse].
AB  - OBJECTIVE: In order to investigate the possible mechanism of its function to
      degrade lipid, we detect the effects of hawthorn flavanone to the influence on
      blood-fat levels and adipogenesis genes transcription expression in fat and
      muscle tissue of hyperlipoidemia mouse. METHOD: In this experiment, a total of 48
      mouse were randomised to four groups and irrigated with two different
      concentrations (1.5 g kg(-1) body weight and 3.0 g kg(-1) body weight) of
      hawthorn flavanone, and killed in 0 h, 1 h, 2 h and 4 h. To estimate the content
      of TC, TG and HCL-C in blood: Total RNA was isolated from adipose and muscle,
      Real-time RT-PCR was used to analyze expression changes of adipogenesis genes
      (SREBP-1c, FAS, HSL and TGH) with time series; to analyze the correlation between
      TG in blood and some kinds of adipogenesis genes and the ratio of FAS/HARMEAN
      (HSL, TGH) mRNA in adipose. RESULT: Hawthorn flavanone was able to cut down the
      level ofTC, TG and HDL significantly in blood and achieved the lowest level at 1
      h. In adipose tissue, hawthorn flavanone up-regulated FAS, HSL and TGH, and
      achieved the level of significance (P<0.05), the expression level of FAS and TGH
      was ascend after 1 h, but HSL descend. The expression level of SREBP-1c was
      descend rapidly and achieved the level of significance after treating with
      hawthorn flavanone at 1 h (P<0.05), after that it rise again to even higher than
      the level of before treatment. After treating with hawthorn flavanone, the ratio
      of FAS/HARMEAN (HSL, TGH) in adipose was significantly descend and achieved the
      lowest level at 1 h (P<0.01), but it was descendsubsequently. In muscle tissue,
      hawthorn flavanone was able to significantly up-regulated the expression of FAS
      and HSL and lower dose group showed greater increasing, the change of SREBP-1c
      was similar in adipose tissue except the more heavily upgrade. CONCLUSION:
      Hawthorn flavanone had the function of depressing the concentration of blood-fat,
      it co-adjusted lipid metabolism of animal by regulating the transcription
      expression of FAS, HSL, TGH and SREBP-1c especially HSL and SREBP-1c
      transcription level.

PMID- 19385192
TI  - [Comparison of distribution of Ophiopogon japonicas polysaccharide in hearts of
      normal rats and myocardial ischemic rats].
AB  - OBJECTIVE: To investigate the distribution of Ophiopogon Japonicas polysaccharide
      (OJP) in hearts of normal rats and myocardial ischemic rats, and obtain the
      further evidences for determining the mechanism of its anti-myocardial ischemia.
      METHOD: Hearts of normal and myocardial ischemic groups were obtained at 5, 10,
      30 and 60 min after once intravenous administration of OJP with the dose of 50
      mg/kg. The concentration of OJP in samples was subsequently determined by HPGPC
      with a fluorescence detector. RESULT: The distribution of OJP in hearts of
      myocardial ischemic rats was much more than that in normal groups at all the
      sampling times. Moreover, the differences were proved to be significant by SPSS
      software with the exception of the situation in the 30 min sampling time.
      CONCLUSION: The enhanced permeability and retention effect caused by ischemia can
      overcome the negative effect of the reduction of blood flow on the distribution
      of OJP from blood into myocardial ischemic zones and actually help OJP target
      myocardial ischemic zones where it can exert its pharmacological effect directly.

PMID- 19385193
TI  - [Properties of energy transfer in two host materials doped with Ir(ppy)3 and
      Rubrene].
AB  - The devices with phosphorescent material tris(2-phenylpyridine)iridium [Ir(ppy)3]
      and fluorescent material 5,6,11, 12-tetraphenylnaphthacene [Rubrene] as dopants
      in two kinds of host were constructed in the present study. Respectively, the two
      kinds of host are polyvinylcarbazole [PVK] and 4,4'-N,N-dicarbazole-biphenyl
      [CBP]. We studied the properties of energy transfer between host materials and
      dopants. Firstly, the absorption and photoluminescence spectra of PVK, CBP,
      Ir(ppy)3 and Rubrene were measured. The spectral overlap between the
      photoluminescence of PVK and the absorption spectrum of Ir(ppy)3 is larger than
      that of Rubrene. The result of the spectral overlap for CBP is the same as PVK.
      It was shown that the energy transfer from the two host materials to Ir(ppy)3 is
      stronger than that to Rubrene. In addition, the energy transfer from Ir(ppy)3 to
      Rubrene is possible according to their absorption and photoluminescence spectra.
      We compared the electroluminescence properties of different devices. In devicel
      of ITO/PVK : Rubrene : Ir(ppy)3 (100 : 5 : x)/BCP(10 nm)/Alq3 (20 nm)/Al and
      device 2 ITO/CBP : Rubrene : Ir(ppy)3 (100 : 5 : x)/BCP(10 nm)/Alq3 (20 nm)/Al(x
      = 0, 3), under the same DC bias, the electroluminescence results show that energy
      transfer from host to Rubrene through Ir(ppy)3 is the main mechanism. And energy
      transfer is much more efficient in CBP as host than in PVK. In addition, at the
      same voltage, the light power of the device doped with Ir(ppy)3 and Rubrene is
      obviously stronger than that of the device doped with Rubrene only. When the
      concentration of Ir(ppy)3 increases, the light power decreases at the same
      voltage, and the effect of concentration quenching is enhanced.

PMID- 19385194
TI  - [Measurement of the Rb[5P3/2(F'=4)] hyperfine level nonradiative decay rate near
      a metallic film with laser retrofluoresence spectroscopy].
AB  - The signals of the hyperfine 85Rb[5P3/2(F' = 2,3,4) --> 5S1/2(F = 3)] transition
      lines in a diode laser induced retrofluorescence spectrum at the interface
      between glass and Rb vapor were experimentally identified and investigated. The
      glass-vapor interface was considered as two distinct regions, a wavelength
      thickness vapor layer joined to the surface and a more remote vapor region. The
      first region was analyzed as a spectral filter that annihilates the absorbed
      photons and the second one as a rich spectral light source. The experimental
      setup is described. A Rb reference cell (T = 293 K) was used. A part of the laser
      beam scanned the 5S1/2(F = 3) --> 5P3/2(F' = 2,3,4) transition. The Doppler
      broadened absorption profile (FWHM = 510 MHz) was determined. The laser detuning
      of the profile-center relative to the F = 3 --> F' = 4 transition was about 70
      MHz. Another laser beam was directed to the entrance cell window. The resonant
      retrofluorescence S(ob)(upsilon(L)) as a function of laser detuning for a cell
      temperature approximately 130 degrees C and laser power 0.4 mW was obtained. We
      can extract the experimental signal sexp(n) (upsilon(L)) originating from the
      near-field region by subtracting signal S(T) (upsilon(L)) originating from the
      far-field region from the total experiment signal S(ob)(upsilon(L)). A fit of the
      normalized profile of the data corresponding to the spectral band centered on the
      F' = 4 --> F = 3 hyperfine transition line was obtained by using a Lorentzian
      distribution function with GammaRF = 50 MHz full width at half-maximum. The role
      played by different relaxation processes contributing to the retrofluorescent
      atomic linewidth was characterized. The authors summed up the corresponding
      spectral broadening and obtained the relation GammaRF = Gamman + Gammacoll +
      Gammanr, where Gammacoll is the resonance collisional broadening of the hyperfine
      line, and Gammanr is an additional broadening induced by the nonradiative energy
      transfer phenomena of the excited atoms near the cell window surface. To evaluate
      Gammacoll, we used the relation Gammacoll = gammaRb - RbN, where gammaRb - Rb is
      line broadening parameter, and N is Rb atom number density. The effective
      nonradiative relaxation rate of the 5P3/2(F' = 4) energy hyperfine level was
      estimated to be AF(nr) = 4 --> F = 3 = 2.4 x 10(8) s(-1). The value of A(nr)
      seems relatively large compared to the spontaneous emission rate A(5P3/2 -->
      5P1/2) = 1.4 x 10(7) s(-1).

PMID- 19385195
TI  - [Open-path online monitoring of ambient atmospheric CO2 based on laser absorption
      spectrum].
AB  - With the conjunction of tunable diode laser absorption spectroscopy technology
      (TDLAS) and the open long optical path technology, the system designing scheme of
      CO2 on-line monitoring based on near infrared tunable diode laser absorption
      spectroscopy technology was discussed in detail, and the instrument for large
      range measurement was set up. By choosing the infrared absorption line of CO2 at
      1.57 microm whose line strength is strong and suitable for measurement, the
      ambient atmospheric CO2 was measured continuously with a 30 s temporal resolution
      at an suburb site in the autumn of 2007. The diurnal atmospheric variations of
      CO2 and continuous monitoring results were presented. The results show that the
      variation in CO2 concentration has an obvious diurnal periodicity in suburb where
      the air is free of interference and contamination. The general characteristic of
      diurnal variation is that the concentration is low in the daytime and high at
      night, so it matches the photosynthesis trend. The instrument can detect gas
      concentration online with high resolution, high sensitivity, high precision,
      short response time and many other advantages, the monitoring requires no gas
      sampling, the calibration is easy, and the detection limit is about 4.2 x 10(-7).
      It has been proved that the system and measurement project are feasible, so it is
      an effective method for gas flux continuous online monitoring of large range in
      ecosystem based on TDLAS technology.

PMID- 19385196
TI  - [A hyperspectral subpixel target detection method based on inverse least squares
      method].
AB  - In the present paper, an inverse least square (ILS) method combined with the
      Mahalanobis distance outlier detection method is discussed to detect the subpixel
      target from the hyperspectral image. Firstly, the inverse model for the target
      spectrum and all the pixel spectra was established, in which the accurate target
      spectrum was obtained previously, and then the SNV algorithm was employed to
      preprocess each original pixel spectra separately. After the pretreatment, the
      regressive coefficient of ILS was calculated with partial least square (PLS)
      algorithm. Each point in the vector of regressive coefficient corresponds to a
      pixel in the image. The Mahalanobis distance was calculated with each point in
      the regressive coefficient vector. Because Mahalanobis distance stands for the
      extent to which samples deviate from the total population, the point with
      Mahalanobis distance larger than the 3sigma was regarded as the subpixel target.
      In this algorithm, no other prior information such as representative background
      spectrum or modeling of background is required, and only the target spectrum is
      needed. In addition, the result of the detection is insensitive to the complexity
      of background. This method was applied to AVIRIS remote sensing data. For this
      simulation experiment, AVIRIS remote sensing data was free downloaded from the
      NASA official websit, the spectrum of a ground object in the AVIRIS hyperspectral
      image was picked up as the target spectrum, and the subpixel target was simulated
      though a linear mixed method. The comparison of the subpixel detection result of
      the method mentioned above with that of orthogonal subspace projection method
      (OSP) was performed. The result shows that the performance of the ILS method is
      better than the traditional OSP method. The ROC (receive operating characteristic
      curve) and SNR were calculated, which indicates that the ILS method possesses
      higher detection accuracy and less computing time than the OSP algorithm.

PMID- 19385197
TI  - [Analysis and experimental verification of sensitivity and SNR of laser warning
      receiver].
AB  - In order to countermeasure increasingly serious threat from hostile laser in
      modern war, it is urgent to do research on laser warning technology and system,
      and the sensitivity and signal to noise ratio (SNR) are two important performance
      parameters in laser warning system. In the present paper, based on the signal
      statistical detection theory, a method for calculation of the sensitivity and SNR
      in coherent detection laser warning receiver (LWR) has been proposed. Firstly,
      the probabilities of the laser signal and receiver noise were analyzed. Secondly,
      based on the threshold detection theory and Neyman-Pearson criteria, the signal
      current equation was established by introducing detection probability factor and
      false alarm rate factor, then, the mathematical expressions of sensitivity and
      SNR were deduced. Finally, by using method, the sensitivity and SNR of the
      sinusoidal grating laser warning receiver developed by our group were analyzed,
      and the theoretic calculation and experimental results indicate that the SNR
      analysis method is feasible, and can be used in performance analysis of LWR.

PMID- 19385198
TI  - [Morphology determination of multi-needle bipolar corona discharge by OES].
AB  - Using the method of OES (optical emission spectrum) for measuring N2 emission
      spectrum, the spacial distribution of energetic electrons in multi-needle bipolar
      corona discharge at atmospheric pressure was investigated. According to the
      distribution of N2 second positive band's intensity ISPB, the outline of
      ionisation region was drawn accurately. The relationship between ISPB and
      discharge current I was obtained through the sum of ISPB. There are two
      ionisation regions in the multi-needle bipolar corona discharge. One is near the
      HV electrode and the other is near the grounded electrode. The ionisation region
      exists around the needlepoint within 2-3 mm. The volume of ionisation region
      becomes big with the applied voltage U increasing. The ionisation region of
      negative corona is bigger than that of positive corona. Near the HV discharge
      electrode, the outline of electron avalanche is similar to the configuration of
      electric field lines in the ionisation region, so the electron avalanche along
      the axis direction of needle develops farther than that along the radial
      direction. The electric field in the migration area is weak, and the distribution
      of space charges is large along the radial direction. The sum of ISPB in each
      ionisation region is second order linear with I, but the quadratic coefficient is
      very small. So the sum of ISPB is nearly linear with I, the distribution of ISPB
      is corresponding to the density distribution of energetic electrons. So the
      charged particles forming the discharge current in ionisation region are
      electrons. No emission spectrum of N2 can be measured in migration area, so there
      is no energetic electron. The energetic electrons only exist in ionisation region
      and the charged particles in migration area are ions.

PMID- 19385199
TI  - [Studies on the determination of the flux of gaseous pollutant from an area by
      passive differential optical absorption spectroscopy].
AB  - An optical remote sensing method based on passive differential optical absorption
      spectroscopy (DOAS) for the determination of the flux of SO2 or other gaseous
      pollutants from an area (such as industrial area, city) which includes many
      different atmospheric pollution sources was studied in the present paper. Passive
      DOAS using the zenith scattered sunlight as the light source provides the column
      density (the integrated concentration of atmospheric absorbers along the light
      path) and has been successfully applied to the determination of the flux of
      gaseous pollutants emitted from the volcano or point source. Passive DOAS
      instrument installed in a car scanned the plume emitted from an area by circling
      around the area in this paper. Column density of each selected gaseous pollutant
      was retrieved from zenith scattered sunlight spectra collected by the instrument
      by spectral analysis method of passive DOAS in their particular absorption
      spectral range respectively. Combined with the meteorological (wind field)
      information during the period of measurement, the net flux value of gaseous
      pollutant from this area during the measurement could be estimated. DOAS method
      used to obtain the column density of gaseous pollutant in the section plane of
      the plume emitted from source and the method of net flux calculation of gaseous
      pollutant from a certain area are described. Also a passive DOAS instrument was
      developed and installed in a car to scan the gaseous pollutants from the area
      surrounded by the 5th Ring Road in Beijing city during a field campaign in the
      summer of 2005. The SO2 net flux 1.13 x 10(4) kg x h(-1) and NO2 net flux 9.3 x
      10(3) kg x h(-1) from this area were derived separately after the passive DOAS
      measured the entire ring road and the wind data were roughly estimated from wind
      profile radar. The results indicate that this optical remote sensing method based
      on passive DOAS can be used to rapidly determine the flux of gaseous pollutant
      (such as SO2, NO2) emitted from an area, especially from a city or an industrial
      area.

PMID- 19385200
TI  - [Multi-wavelength spectral aerosol scale height in inshore in contrast with that
      in inland].
AB  - In the present paper, based on the exponential attenuation of atmospheric aerosol
      concentration with height, so using continuous spectrum sun-photometer, forward
      scatter visibility sensor and hygrothermograph, the authors measured the
      atmosphere column optical characteristic and plane spectral extinction
      coefficient on earth on the base of two experiments at some edge of ocean at the
      same time, respectively, set up the calculative method of multi-wavelength
      spectral aerosol scale height. Firstly, the authors obtained atmospheric
      horizontal extinction coefficient with forward scattering visibility sensor,
      which subtracted molecular extinction coefficient, and could get aerosol
      extinction coefficient near ground; Then, selecting sea salt model, using OPAC
      software, the authors also could calculate the aerosol extinction coefficient
      under different humidity (0%, 50%, 70%, 80%, 90%, 95%, 98% and 99%) and different
      wavelength (400, 450, 500, 550, 600, 650, 700 and 750 nm), the aerosol extinction
      coefficient was detected by visibility sensor, using interpolation method,
      respectively; Finally, using the data of atmospheric columniation optical
      thickness detected by continuous spectral sun-photometer and subtracted molecular
      optical thickness corresponding wavelengths were accounted out by Modtran 4. 0.
      The authors obtained the characteristic of spectral aerosol scale height of
      visible light (wavelength is 400, 440, 532, 550 and 690 nm): with wavelength
      increments, and spectral aerosol scale height was found to decline neither in
      inland nor in inshore in China; Spectral aerosol scale height in winter is higher
      than in summer in southeast inshore; but spectral aerosol scale height in winter
      is smaller in summer than in inland.

PMID- 19385201
TI  - [Algorithm for estimating chlorophyll-a concentration in case II water body based
      on bio-optical model].
AB  - In the present study, a novel retrieval method for estimating chlorophyll-a
      concentration in case II waters based on bio-optical model was proposed and was
      tested with the data measured in the laboratory. A series of reflectance spectra,
      with which the concentration of each sample constituent (for example chlorophyll
      a, NPSS etc.) was obtained from accurate experiments, were used to calculate the
      absorption and backscattering coefficients of the constituents of the case II
      waters. Then non-negative least square method was applied to calculate the
      concentration of chlorophyll-a and non-phytoplankton suspended sediments (NPSS).
      Green algae was firstly collected from the Kasumigaura lake in Japan and then
      cultured in the laboratory. The reflectance spectra of waters with different
      amounts of phytoplankton and NPSS were measured in the dark room using FieldSpec
      Pro VNIR (Analytical Spectral Devises Inc. , Boulder, CO, USA). In order to
      validate whether this method can be applied in multispectral data (for example
      Landsat TM), the spectra measured in the laboratory were resampled with Landsat
      TM bands 1, 2, 3 and 4. Different combinations of TM bands were compared to
      derive the most appropriate wavelength for detecting chlorophyll-a in case II
      water for green algae. The results indicated that the combination of TM bands 2,
      3 and 4 achieved much better accuracy than other combinations, and the estimated
      concentration of chlorophyll-a was significantly more accurate than empirical
      methods. It is expected that this method can be directly applied to the real
      remotely sensed image because it is based on bio-optical model.

PMID- 19385202
TI  - [Spectra analyses of chitosans degraded by hydrogen peroxide under optimal
      conditions].
AB  - Chitosans with different average molecular weight (1,500-156 kDa) were prepared
      under optimal conditions based on our previous research by the depolymerization
      of initial chitosan using hydrogen peroxide, with maintaining the native
      structure of natural chitosan as principal consideration. Nitrogen and Carbon
      components of initial chitosan and degraded products were analyzed by BUCHI fully
      automatic nitrogen determination system and Liquid total organic carbon (TOC)
      analyzer respectively. Fourier transform infrared (FTIR), 13C nuclear magnetic
      resonance (13C NMR), X-ray diffraction and circular dichroism (CD) analyses were
      used to characterize the structure properties of samples. The results indicated
      that the maximum standard deviations of carbon content and nitrogen content and
      the degree of deacetylation (DD) of degraded products with the corresponding
      values of the initial chitosan are 2.4%, 2.3% and 6.9% respectively. Besides, the
      differentiations of the nitrogen content and DD value of the degraded product
      with the corresponding values of the initial chitosan are narrowed with the
      increase in the reaction time. FTIR spectra of resulting products are similar to
      that of initial chitosan in terms of peak number and position, indicating that
      there are no other functional groups formed during the degradation. 13C-NMR
      analyses of initial chitosan and degraded products revealed that the chemical
      structures of resulting chitosans are not changed to any noticeable extent. X-ray
      diffraction patterns of initial chitosan and degraded chitosans are alike and
      show characteristic peaks at 2theta = 10. 4 degrees and 19.8 degrees under the
      condition that the initial chitosan was disposed as degraded chitosans. Circular
      dichroism analyses showed that all the samples exhibit a broad negative band
      located at about 210 nm assigned to n --> pi* electronic transition of the --NH-
      CO-- chromophore on a glycosidic ring in acidic media, which demonstrated that
      degraded chitosans maintain their natural conformation in liquid state
      substantially. All these confirmed that the degraded chtiosans maintain their
      natural structure and conformation, and the breakage of beta-1,4-glucoside bonds
      in macromolecule is the basic process under optimal degradation conditions.

PMID- 19385203
TI  - [Study on the preparation and spectral characteristics of Bi2S3 nanoribbons].
AB  - In the present study, bismuth sulfide (Bi2S3) nanoribbons were prepared by the
      hydrothermal method using bismuth nitrate (Bi(NO3)3 x 5H2O), thioacetamide
      (C2H5NS) and nitrilotriacetic acid (C6H9NO6) as raw materials at 180 degrees C
      for 12 h. The reaction time was largely reduced and the route has been
      unreported. The constituent, structure and morphology of the products were
      characterized by XRD, XPS and TEM, respectively. The powder X-ray diffraction
      (XRD) pattern shows that the Bi2S3 crystals belong to the orthorhombic phase
      (JCPDS:17-320) with calculated lattice constants a = 1.1106 nm, b = 1.0993 nm and
      c = 0.3892 nm, which are consistent with the reported values (a = 1.1149 nm, b =
      1.1304 nm and c = 0.3981 nm). Transmission electron microscopic (TEM) studies
      reveal that the appearance of as-prepared Bi2S3 is nanoribbon-like with the
      typical width of about 100 nm; and the high-resolution transmission electron
      microscope (HRTEM) image shows that the crystal grows along the y axis. The
      quantification of X-ray photoelectron spectra (XPS) analysis peaks gives an
      atomic ratio of 2 : 3 for Bi : S, which is consistent with the given formula of
      Bi2S3. Furthermore, the Raman and UV-Vis spectra of the product were also
      studied. Compared with bulk Bi2S3 (236 cm(-1)), the Raman absorption band of the
      Bi2S3 nanoribbons (195 cm(-1)) red-shifts 41 cm(-1), which is because of the
      surface effect of nanomaterials. Furthermore, the product has absorption at the
      wavelength of about 450 nm in the UV-Vis region. The direct bang gap energy (Eg)
      was estimated to be about 1.58 eV(Eg of the bulk Bi2S3 is 1.3 eV), which
      indicates that the product has potential application in the optical and
      electrical areas.

PMID- 19385204
TI  - [Preparation of surface-modified carbon nanotubes/silica composite gel glass].
AB  - Owing to their unique structure and properties, carbon nanotubes (CNTs) have
      become the highlight of research since they were discovered. Part of the research
      interest lies in introducing them into solid state matrix to make them
      materialized. However, CNTs tend to aggregate in the matrix, which makes it
      difficult to make homogeneous composites. In order to solve this problem, we
      first modified the surface of CNTs by chemically bonding them to 3
      aminopropyltrie-thoxysilane (NH2 (CH2)3Si(OC2H5)3, APTES) using three-step
      reactions, and then connected them to silica network by sol-gel technique. In the
      present paper, CNTs were first treated with HNO3 to get CNTs-COOH, which were
      then treated with SOCl2 to be transferred to CNTs-COCl, and finally CNTs-COCl
      reacted with APTES to get CNTs-APTES. After that, CNTs were introduced into
      silica net work through the individual hydrolysis of CNTs-APTES,
      tetrathyloxysilane (Si(OC2H5)4, TEOS) and 3-glycidoxy-propltrimethoxysilane
      (CH2OCHCH2O(CH2)3Si(OCH3)3, GPTMS) as sol-gel precursors, and the
      copolymerization of their hydrolysis products. FTIR and SEM were used to
      characterize the composition and microstructure of the obtained samples. (Owing
      to the connection of CNTs with silica network, little aggregation of CNTs was
      observed and high-quality CNTs/SiO2 composite gel glass was obtained. A model of
      CNTs/SiO2 network was also given.

PMID- 19385205
TI  - [Research on the polycrystalline CdS thin films prepared by close-spaced
      sublimation].
AB  - In the present paper, the factors of influence on the deposition rate of CdS
      films prepared by close-spaced sublimation (CSS) were first studied
      systematically, and it was found from the experiments that the deposition rate
      increased with the raised temperature of sublimation source, while decreased with
      the raised substrate temperature and the deposition pressure. The structure,
      morphology and light transmittance of the prepared samples were tested
      subsequently, and the results show: (1) The CdS films deposited under different
      oxygen partial pressure all present predominating growth lattice orientation
      (103), and further more the films will be strengthened after annealed under CdCl2
      atmosphere. (2) The AFM images of CdS show that the films are compact and uniform
      in grain diameter, and the grain size becomes larger with the increased substrate
      temperature. Along with it, the film roughness was also augmented. (3) The
      transmittance in the shortwave region of visible light through the CdS films
      would be enhanced when its thickness is reduced, and that will help improve the
      shortwave spectral response of CdTe solar cells. Finally, the prepared CdS films
      were employed to fabricate CdTe solar cells, which have achieved a conversion
      efficiency of 10.29%, and thus the feasibility of CSS process in the manufacture
      of CdTe solar cells was validated primarily.

PMID- 19385206
TI  - [Research on laser spectrum detecting technology based on static Mach-Zehnder
      interferometer].
AB  - It is the key content of laser warning to reliably and real-time detect the type
      and characteristic parameters of incident laser. Coherent detection technology
      detects the information based on the coherence of laser, and is a kind of
      effective detection technology. In order to detect the incident laser's spectrum,
      a kind of device for laser detecting and real time spectrum measurement was
      designed, which measures the laser spectrum on the bases of coherent detecting
      technology, Fourier optics and optical signal processing. Using compact and
      static Mach-Zehnder interferometer as the coherent detection components, it can
      restrain the background light efficiently. The non-scanning mechanical parts
      allow fast spectrum detection, and narrow laser pulse can be detected. The real
      time signal processing is realized by DSP and multi-channel frame subtraction
      technology to wipe off the background light, detect the laser and measure its
      spectrum. The result indicates that, using Mach-Zehnder interferometer and multi
      channel frame subtraction technology can realize the laser pulse detection, and
      improve the measuring precision efficiently; 10 ns laser pulse can be detected
      and the wavelength measuring error is less than 10 nm.

PMID- 19385207
TI  - [Extracting projections from laser moire interference spectra].
AB  - Laser Moire Interference spectra of rocket exhausted plumes were analyzed.
      Projections for reconstruction were figured out, and air density distribution was
      reconstructed. Moire deflectograms of the plumes were produced and captured with
      a home-made, wide-range, high-sensitivity Moire deflectometer. Moire interference
      spectra were processed by phase unwrapping technique with Fourier transform, so
      the space phase distribution of Moire deflectograms was extracted. The background
      was worked out based on the margin of the Moire deflectograms, and so was the
      space phase distribution of the background. The phase shift distribution of
      distorted Moire interference spectra could easily be obtained by calculating the
      difference between the two space phase distributions. The relative projections
      could be extracted from the phase shift distribution. The air density
      distribution of the plumes was calculated by simple self-correlative algebraic
      reconstruction technique (SSART) based on deflected angles for projections. Eight
      projections with equal direction interval of 20 degree were used for
      reconstructing the air density distribution of a plume section. As a result, with
      phase unwrapping technique based on Fourier transform, any cross section
      projection could conveniently be worked out from the Moire deflectogram of rocket
      exhausted plumes. The air density distribution of the cross section could be
      reconstructed by SSART. So, SSART with deflected angle for projection is a kind
      of super nonlinear deflection tomography.

PMID- 19385208
TI  - [Study of spectra characteristics of Ca3SiO5 : Eu2+ phosphor].
AB  - The Ca3SiO5 : Eu2+ phosphor was synthesized by the sol-gel reaction method. The
      emission spectrum was measured by a SPEX1404 spectrophotometer, and the
      excitation spectrum was measured by a SHIMADZU RF-540 ultraviolet
      spectrophotometer. All the characterization of the phosphors was conducted at
      room temperature. The results show that the emission spectrum of Ca3SiO5 : Eu2+
      phosphor exhibits one asymmetry band centred at 505 nm under the 365 nm
      excitation, and the excitation spectrum for 505 nm indicates two bands centred at
      374 and 397 nm, respectively. The above results indicate that the phosphor used
      for w-LEDs can be excited by UV light, and emit green light. The effect of
      synthesis condition, such as synthesis temperature, synthesis time and Eu2+
      concentration, on the emission spectrum of Ca3SiO5 : Eu2+ phosphor was
      investigated. The results show that the emission peak intensity of Ca3SiO5 : Eu2+
      phosphor firstly increases, then decreases with the increase in synthesis
      temperature or synthesis time or Eu2+ concentration, and reaches the maximum
      value at 1,100 degrees C, for 4 h and 0.5 mol% Eu2+.

PMID- 19385209
TI  - [Determination of pazufloxacin mesylas by terbium sensitized chemiluminescence
      method].
AB  - Tb3+ can form chelate with pazufloxacin mesylas (PM), and the complex of terbium
      pazufloxacin mesylas(Tb3+-PM) can sensitize the chemiluminescence (CL) intensity
      of KMnO4-Na2SO3 system through energy transfer. Based on the chemiluminescence
      reaction, a new sensitized chemiluminescence method was developed for the
      determination of PM by flow-injection. Under the optimum conditions, the enhanced
      CL intensity was linear with the concentration of PM in the range of 0.10-12 mg x
      L(-1) with the detection limit of 0.04 mg x L(-1). The relative standard
      deviation for eleven continuous determinations of 1.0 mg x L(-1) PM was 1.9%.
      This method has been applied to the determination of PM in injection and body
      fluid with satisfactory results. This method has the merits of simpleness,
      speediness, sensitivity and good reproducibility. An original mechanism was
      proposed to explain this phenomenon.

PMID- 19385210
TI  - [Spectroscopy study of binding mechanisms and molecular recognition of
      methamidophos-specific moleculary imprinted polymer].
AB  - A new methamidophos-specific molecularly imprinted polymer (MIP) was synthesized
      based on non-covalent interaction. The complexes formed between MAP and MAA were
      evaluated by 1H NMR, FTIR and UV spectrometry. The MAP-MAA complexes of 1 : 2
      mole ratio were obtained by cooperative hydrogen bonding and the complexes
      possessed better stabilization (K = 2.894 x 10(6) L2 x mol(-2). The Infrared
      spectrometry differences of the MIPs before and after saturated with MAP further
      indicated that there were carboxyl functional groups in the MIP, which could
      interact with the template by cooperative hydrogen bonding specifically.

PMID- 19385211
TI  - [FTIR assessment of the secondary structure of proteins in royal jelly under
      different storage conditions].
AB  - The quality of royal jelly has a high positive correlation with its storage
      periods and temperature. In the present paper, Fourier transform infrared spectra
      (FTIR) of royal jelly was measured with different temperatures and storage
      periods, and the compositions of the secondary structure of protein were
      determined by curve-fitting analysis of the amide I bands in the FTIR spectra.
      The results showed that the spectral differences were observed among these types
      of samples, the composition of the secondary structures of protein exhibited
      extreme difference, and the rate of alpha-helix decreased and beta-sheet
      increased dramatically with the increase in storage temperature and periods. The
      content of beta-turn also tended to increase, and the order of their change
      extent was 28 degrees C > 16 degrees C > 4 degrees C > -18 degrees C. These
      results met the theory that royal jelly should be kept under lower temperature.
      So, FTIR spectroscopy combined with several data-processing methods, such as
      secondary derivative, deconvolution, and curve fitting would be an effective
      method for assessing the quality and freshness of royal jelly.

PMID- 19385212
TI  - [Characterization of structure of carboxymethylpachymaran by IR spectrum and
      atomic force microscopy].
AB  - The structure of Carboxymethylpachymaran was characterized using Fourier
      transform infrared spectroscopy. Morphological changes of carboxymethylpachymaran
      (CMP) were observed under different solution conditions by atomic force
      microscopy (AFM). After the carboxymethylation, the solubility of pachyman in the
      water was significantly increased, its beta-D-glucan characteristic absorption
      peak at 890 cm(-1) became weak obviously, and its methylene vibration absorption
      peak and C = O antisymmetrical stretch vibration absorption peak appeared at
      1,333 and 1,606 cm(-1) respectively, which indicated that the carboxymethylation
      succeeded. The analysis of AFM results showed that CMP molecules existed in
      different morphology under different solution conditions, and that the
      concentration, ionic strength and solvent physical chemistry characteristics of
      polysaccharide solution had effects on the CMP chains conformation and the action
      mode between different molecular chains. The phenomena were considered to be
      related to hydrogen bond association and intramolecular and intermolecular
      electrostatic interactions of CMP. Meanwhile, the affinity and electrostatic
      interaction between CMP molecules and the mica substrate also had an influence on
      the CMP chains conformation and the image quality.

PMID- 19385213
TI  - [Study on traditional Chinese medicine extracts of rhizoma coptidis by FTIR
      spectroscopy].
AB  - In the present paper, we applied Fourier transform infrared spectroscopy (FTIR)
      and second derivative infrared spectroscopy to establish a rapid and efficient
      analytical method for a preliminary quality control of medicinal herb extracts.
      The commonly used Chinese herb medicine, Rhizoma coptidis, was taken as an
      example. The main component-berberine in rhizoma coptidis was analyzed as target
      compound. The results indicated that the IR spectra of rhizoma coptidis herb, its
      water and alcohol extracts, exhibit their macroscopic fingerprint characters with
      fine repeatability, and the corresponding secondary derivative spectra further
      confirmed the spectral characteristics of the original IR spectra by enhancing
      spectral resolution. The typical and strongest absorption band of IR spectrum of
      berberine is at 1,505 cm(-1), which is assigned to aromatic skeleton vibration
      band, and its intensities in spectra of rhizoma coptidis herb and its different
      extracts become the main identification standard of the contents of berberine in
      those samples. In addition, comparing the IR spectra of the medicinal herb and
      its extracts, it was shown that the main bioactive components, alkaloids in
      rhizoma coptidis herb, are enriched by extraction, and the contents of berberine
      in alcohol extracts of rhizoma coptidis are higher than those in water extracts.
      The spectroscopic technique described is a simple and rapid analytical technique,
      which could provide valuable information about chemical constituents of medicinal
      extracts for guiding further chromatographic analysis and separation improvement.

PMID- 19385214
TI  - [Infrared spectroscopic study on the component and vigor analysis of Cistanche
      deserticola seeds].
AB  - Comparative study of the different parts of cistanche deserticola seeds and their
      changes after different processing were examined by Fourier transform infrared
      spectroscopy spectra (FTIR). The results of the analysis showed that components
      in the cistanche deserticola seeds were abundant, which contained characteristic
      absorption peaks of protein, fat and carbohydrate. As well, pectin and aromatic
      compound can be also found in the seeds. However, the components were different
      in different parts of cistanche deserticola seeds. The characteristic absorption
      peak intensities of fat at 2,926, 1,746, 1,161 and 721 cm(-1) were the strongest
      in the seed kernels. However, the seed coats mainly consisted of carbohydrate and
      pectin, which were showed at 1,054 cm(-1). The contents of protein and
      carbohydrate were decreased distinctly in the moldy and dead seeds after
      processing. The characteristic absorption peak intensity ratio of protein to fat
      (I1,630/I1,745 ) was all higher than 1.05 in the live seeds. The characteristic
      absorption peak intensity ratio of amido link I of protein to fat (11,653/I1,745)
      in the dead seed kernels of the cistanche deserticola was decreased from 0.31 to
      0. 23, which was 25.8% less than that in vital seed kernels. The results suggest
      that FTIR not only can be used in fast comprehensive analysis of seed components,
      but also can be used in the seed vigor analysis, seed longevity determination and
      seed quality evaluation.

PMID- 19385215
TI  - [Visible/NIR analysis of fat, protein and water in chilled pork].
AB  - Fat, protein and water were determined by visible and NIR transmittance
      spectroscopy in chilled pork. After preprocessed by multiplicative scatter
      correction (MSC), the quantitative analysis models were developed based on the
      original, first derivative and second derivative spectra by using partial least
      squares (PLS) at the temperatures of 0-4 degrees C and 20 degrees C,
      respectively. By comparing the correlation coefficient (r), RMSEC, and SEP, we
      found that the first derivative model was the best, and the performance for 0-4
      degrees C was better than that for 20 degrees C. At 0-4 degrees C and 20 degrees
      C, the correlation coefficients were 0.950 and 0.924 for fat, 0.713 and 0.455 for
      protein and 0.944 and 0.914 for water respectively, SEP values were 2.41 and 2.95
      for fat, 5.44 and 4.25 for protein, and 2.37 and 2.38 for water respectively. The
      results showed that the visible and NIR analysis could measure the fat and water
      contents in chilled pork well, but was bad for protein, and this was caused by
      processing line of chilled pork. What's more, the spectrum offset was found in
      the original spectra at about 770 nm to be about 10 nm.

PMID- 19385216
TI  - [Measuring fatty acid concentration in maize grain by near-infrared reflectance
      spectroscopy].
AB  - The fatty acid concentrations in maize grain were analyzed with a set of 294
      samples including normal inbred lines, high-oil inbred lines and high-oil
      recombinant inbred lines (RIL). The method of partial least squares (PLS)
      regression with internal cross validation was employed to develop the measuring
      models of near-infrared reflectance spectroscopy (NIRS) for concentrations of
      four major fatty acids, palmitic, stearic, oleic and linoleic acids, as well as
      oil concentration in maize grain. The NIRS models were accurate for oleic acid,
      linoleic acid and oil concentrations. The determination coefficients of these
      models in cross validation were 0.89, 0.88 and 0.91, respectively; the
      determination coefficients in external validation were 0.86, 0.84 and 0.92,
      respectively; and the ratio of standard deviation (SD) to root mean square error
      of validation (RMSEV) in both calibration and external validation sets (RSC(P))
      was higher than 2.5. But the models for palmitic and stearic acid concentrations
      were not accurate enough with determination coefficients in cross validation and
      external validation lower than 0.80, and RSC(P) lower than 2.5. Further practical
      validation showed that the predicted results by using NIRS models for oleic acid,
      linoleic acid and oil concentrations were accurate and reliable, which will be a
      useful approach to the measurement of a large number of breeding samples during
      genetic improvement of oil quality and quantity in maize.

PMID- 19385217
TI  - [FTIR and classification study on the powdered milk with different assist
      material].
AB  - The near infrared spectrum atlases of milk powders mingled with different
      adjuvant are the object for cluster analysis. Drawing assistance from the
      disparity in infrared fingerprint atlas that change according to the contents of
      chemical constituent, and making mingled component models, the milk powders
      mingled with different adjuvant were taken for a rapid sorting test using SIMCA
      clustering analytical method. In the experiment, two hundred fifty sorts of milk
      powders in the markets from different manufacturers were scanned by near infrared
      ray, and were tested with reproducibility determination. It was found difficult
      to extract fingerprint characters just from the external appearance of the near
      infrared spectrum atlases from milk powders mingled with different adjuvant, and
      it is needed to adopt pattern recognition technique to determine intelligently.
      One hundred sixty atlases were drawn out randomly for cluster analysis, and
      unknown samples were pretested. Results showed that the milk powders mingled with
      different adjuvant can be identified by near infrared spectrum analysis
      associated with cluster analysis methods, notwithstanding the similar near
      infrared spectrum atlases of different sample were difficult to identify
      directly. No overlapping phenomenon was found among milk powders mingled with
      different adjuvant, and they did not interfere with each other. The results from
      clustering spectra between samples were satisfactory, and the correct ratios of
      blind detections were over 90%. In addition, the correct ratios of this method
      may be elevated remarkably with sufficient number of samples, increasing training
      set sample quantity and sampling representation, and strengthening the standard
      degree of manipulation. It is concluded that the designed model to determine milk
      powders mingled with different adjuvant is rational, and the determination
      capability is fine.

PMID- 19385218
TI  - [Analysis of visible and near-infrared spectra of As-contaminated soil in
      croplands beside mines].
AB  - Soil samples in the depth from 0 to 20 cm were scooped from agricultural region
      beside mines and prepared for determination of As concentration, Fe
      concentrations and organic matter content. At the same time they were scanned by
      mobile hyperspectral radiometer for visible and near-infrared spectra. Savitzky
      Golay filter was used to smooth noises in spectrum curve because of some low
      signal-to-noise ratios in some regions of visible and near-infrared light, and
      all the spectra were resampled with the spectral interval of 10 nm. Before
      principal component regression and partial least square regression models were
      constructed for predicting As concentration, Fe concentrations and OM content,
      several spectral preprocessing techniques like first/second derivative (F/SD),
      baseline correction (B), standard normalized variate (SNV), multiplicative
      scatter correction (MSC) and continuum removal (CR) were used for promotion of
      models' robustness and predicting performance. For limited samples, cross
      validation was carried out by repeated leave-one-out procedure, and root mean
      square error of prediction (RMSEP) was used for validating the prediction ability
      of constructed models. In this study principal component regression models behave
      better than partial least square regression models in representing regressing
      ability, reducing risk of over-fitting with less factors and ensuring models'
      accuracy and pertinences (relative RMSEP and R2). Preprocessing techniques of
      SNV, MSC and CR improve obviously the prediction ability of models for As
      concentration, Fe concentrations and OM content with relative RMSEP equal to
      0.3040, 0.1443 and 0.1712, with number of factors equal to 5, 3 and 3,
      respectively. The analysis of regression vectors of selected optimal PCR models
      shows that several important wavelengths are simultaneously taken and helpful for
      prediction performance: 450, 1,000, 1,400, 1,900, 2,050, 2,200, 2,250, 2,400 and
      2,470 nm. Application of the calibrated models to soil contamination of croplands
      is promising. Concentrations of soil contaminants and contents of other matter
      can be determined by reflectance spectroscopy with high spectra resolution, which
      would provide potent reference for remote sensing monitoring of soil and
      environmental quality.

PMID- 19385219
TI  - [Characterization of kale (Brassica oberacea var acephala) under thallium stress
      by in situ attenuated total reflection FTIR].
AB  - The experiment was designed based on consumption of carbon dioxide through the
      photosynthesis of Brassica oberacea var acephala leaf, and the photosynthesis of
      kale leaf under thallium stress was investigated by in situ attenuated total
      reflection FTIR (in situ ATR-FTIR). The ATR-FTIR showed that the absorption peaks
      of leaves had no obvious difference between plants growing in thallium stress
      soil and plants growing in non-thallium pollution soil, and the strong peaks at
      3,380 cm(-1) could be assigned to the absorption of water, carbohydrate, protein
      or amide; the strong peaks at 2,916 and 2,850 cm(-1) assigned to the absorption
      of carbohydrate or aliphatic compound; the peaks at 1,640 cm(-1) assigned to the
      absorption of water. However, as detected by the in situ ATR-FTIR, the double
      peaks (negative peaks) at 2,360 and 2,340 cm(-1) that are assigned to the
      absorption of CO2 appeared and became high gradually. It was showed that kale was
      carrying photosynthesis. At the same time, the carbon dioxide consumption speed
      of leaf under thallium stress was obviously larger than that of the blank It was
      expressed that photosynthesis under thallium stress was stronger than the blank
      All these represented that kale had certain tolerance to the heavy metal
      thallium. Meanwhile, the carbon dioxide consumption of grown-up leaf was more
      than that of young leaf whether or not under thallium stress. It was also
      indicated that the intensity of photosynthesis in grown-up leaf is higher than
      that in young leaf.

PMID- 19385220
TI  - [Progress in application of near infrared spectroscopy to nondestructive on-line
      detection of products/food quality].
AB  - Increasing safety events caused by products/food quality problems has caught more
      and more attention, therefore non-destructive fast detection of products/food
      quality becomes necessary. At present, fast detection methods commonly used
      include chemical colorimetric method, near infrared spectroscopy (NIRS)
      technique, immunoassay method, bio-sensor technique, biomicroarray method,
      bioluminescence method, and so on. NIRS technique has found wide application in
      products/food quality detection because of its characteristics such as very high
      speed, no sample preparation, non-destruction, no pollution, low cost etc. Many
      research works have been done on products/food quality detection using NIRS
      technique both home and abroad, from static laboratory investigations to online
      investigations. In the present paper, basic knowledge of NIRS and its analysis
      process were briefly introduced. The applications of NIRS technique in online
      quality detection and control of fruit, fish, meat, milk, grain, fermentation of
      cheese and alcohol etc were reviewed. Finally, the existing problems of NIRS were
      pointed out and the prospect of NIRS technique was discussed. In the future, NIRS
      technique will combine with network technique to realize online update and
      upgrade of NIR models. And spectral imaging technique will be the development
      trend of NIRS technique in the 21st century.

PMID- 19385221
TI  - [Multiple dependent variables LS-SVM regression algorithm and its application in
      NIR spectral quantitative analysis].
AB  - In the present paper, on the basis of LS-SVM algorithm, we built a multiple
      dependent variables LS-SVM (MLS-SVM) regression model whose weights can be
      optimized, and gave the corresponding algorithm. Furthermore, we theoretically
      explained the relationship between MLS-SVM and LS-SVM. Sixty four broomcorn
      samples were taken as experimental material, and the sample ratio of modeling set
      to predicting set was 51 : 13. We first selected randomly and uniformly five
      weight groups in the interval [0, 1], and then in the way of leave-one-out (LOO)
      rule determined one appropriate weight group and parameters including penalizing
      parameters and kernel parameters in the model according to the criterion of the
      minimum of average relative error. Then a multiple dependent variables
      quantitative analysis model was built with NIR spectrum and simultaneously
      analyzed three chemical constituents containing protein, lysine and starch.
      Finally, the average relative errors between actual values and predicted ones by
      the model of three components for the predicting set were 1.65%, 6.47% and 1.37%,
      respectively, and the correlation coefficients were 0.9940, 0.8392 and 0.8825,
      respectively. For comparison, LS-SVM was also utilized, for which the average
      relative errors were 1.68%, 6.25% and 1.47%, respectively, and the correlation
      coefficients were 0.9941, 0.8310 and 0.8800, respectively. It is obvious that MLS
      SVM algorithm is comparable to LS-SVM algorithm in modeling analysis performance,
      and both of them can give satisfying results. The result shows that the model
      with MLS-SVM algorithm is capable of doing multi-components NIR quantitative
      analysis synchronously. Thus MLS-SVM algorithm offers a new multiple dependent
      variables quantitative analysis approach for chemometrics. In addition, the
      weights have certain effect on the prediction performance of the model with MLS
      SVM, which is consistent with our intuition and is validated in this study.
      Therefore, it is necessary to optimize weights in multiple dependent variables
      NIR modeling analysis.

PMID- 19385222
TI  - [XRD and FTIR spectra characteristics of nacreous layer in perna viridis].
AB  - The XRD and FTIR of aragonites in nacreous and prismatic layer of perna viridis
      were systematically measured, and the frequency variations of v1, v2 and v4 band
      of aragonites were especially analyzed. The results showed that both of them were
      aragonite and the frequency of v2 band differed in them, but the frequencies of
      other two bands were not altered and had the same values with cavernous
      aragonite. In the same specie of shell, the frequency of v2 band in nacreous
      layers was greater than that in prismatic layers, and there was a frequency shift
      of v2 band between them. For the first time, the phase transformation of biogenic
      aragonite was detected. After nacreous aragonite was heated at 300 degrees C, the
      frequency shift of v2 band was found. So it is concluded that the biogenic
      aragonite is related to the thermal effects in crystallizing process, meanwhile
      it stores excess energy. All of these can provide experiential basis for studying
      biomineralization theory.

PMID- 19385223
TI  - [FTIR and XRD analysis of the enzymatic degradation of crosslinked starch
      microspheres].
AB  - Crosslinked starch microspheres (CSM) were prepared by crosslinking of soluble
      starch and N, N'-methylene-bis-acrylamide in inverse suspension. In order to
      describe the enzymatic degradation of CSM in this experiment, soluble starch, CSM
      and CSM's degradation product obtained from the simulated intestinal fluid in
      different time were analysed by Fourier transform infrared spectroscopy (FTIR)
      and X-ray diffractometer (XRD). The FTIR and SEM results showed that the CSM's
      crosslinking structure could be maintained steady in digested liquid within 3
      hours. The intensity at 1,090 cm(-1) related to bending vibration bands of C--O-
      C, the amide band I and the amide band II became weaker in 3-12 hours along with
      the process of the enzymatic degradation, indicating the degradation of the
      molecular chain of starch and the depolymerization of the cross-linking
      structure. And then the disappearing of the amide band I and the amide band II
      indicated that the crosslinking structure was totally destructed after 12 hours
      and thereafter the enzymatic degradation was consistent with soluble starch. The
      XRD results proved that after 12 hours the CSM's degradation was similar to
      starch's degradation, their non-crystalline parts were decomposed, and their
      degree of crystallinity increased with the development of the degradation, but
      did not exceed the crystallinity of soluble starch.

PMID- 19385224
TI  - [LO phonon-plasmon coupled mode in hexagonal IngaN alloy].
AB  - Raman scattering spectra of hexagonal InGaN/GaN film, excited with 532 and 488 nm
      visible laser lines and 325 nm UV laser line, were investigated at room
      temperature and 78 K. The sample was grown by metalorganic chemical vapor
      deposition on a sapphire substrate. Excited with 532 and 488 nm visible laser
      lines, the E2 and A1 (LO) modes were observed at about 571.3 and 736.4 cm(-1),
      respectively. These scattering signals mainly originate from GaN layer. Excited
      with 325 nm UV laser line, the E2 mode shifts to 569.7 cm(-1), while A1 (LO) mode
      shifts to 730.3 cm(-1) and resonance is enhanced. These scattering signals
      originate from InGaN layer. A broad feature at high frequency of A1 (LO) mode was
      observed in spectroscopy excited with visible laser line, and was attributed to
      the LO phonon-plasmon coupled mode of InGaN layer. The electron concentration of
      InGaN film determined from the frequency of the coupled mode is ne = 1.61 x
      10(18) cm(-3). Excited with 325 nm UV laser light, the LO phonon-plasmon coupled
      mode is absent, and the scattering signal of A1 (LO) mode mainly originates from
      the surface depletion layer of the sample. The thickness of the surface depletion
      layer is about 40 nm. Furthermore, the scattering intensities of LO phonon
      plasmon coupled mode at room temperature and 78 K were compared and analyzed. The
      screening wave vectors of plasmon at different temperatures were calculated. At
      low temperature, the screening wave vector increases, the damping of the plasmon
      decreases, so the LO phonon-plasmon coupled mode becomes stronger. This work is
      helpful in understanding the property of InGaN and in developing the
      optoelectronic devices of nitride.

PMID- 19385225
TI  - [A study of Raman spectra denoising based on empirical mode decomposition].
AB  - The multiresolution empirical mode decomposition (EMD) is a new method of
      analyzing signal. It can be interpreted as a temporal and spatial filtering based
      on the extremum characteristic scale of the signal. This method can preserve the
      nonlinearity and non-stability of signal, and has potential superiority in
      filtering and denoising. In the present paper, a new denoising method of Raman
      spectra on the basis of empirical mode decomposition with multiresolution
      filtering is presented. First, Raman spectra polluted by the white noise is
      decomposed into several intrinsic mode function (IMF) components of different
      time scale based on empirical mode decomposition (EMD). Then, the IMF components
      of high frequencies are preprocessed using the threshold method, and we add these
      IMF components to the IMF components of low frequencies to achieve denoising
      signal. For various noise levels, the effects of three methods (the EMD threshold
      denoising, the wavelet threshold denoising and the EMD low-pass filtering) are
      analyzed by processing the noisy p-xylene spectra. The results show that the EMD
      threshold denosing method eliminates the noise effectively. In addition, this
      method also preserves the detailed information of the original spectra well. By
      contrast with the wavelet threshold denosing method, the EMD threshold denoising
      requires no prior knowledge about the sample composition and no selection of the
      suitable decomposition level, and the adaptation is in evidence. The new method
      will have a good application prospect in Raman spectra denoising.

PMID- 19385227
TI  - [Study on concentration quenching and energy transfer in Ln3+ (Ln = Tb, Tm, Eu)
      in Y2O3 nanocrystal powders].
AB  - Nano-powders Y2O3 with various particle sizes and different doping concentrations
      of Ln (Ln = Tb, Tm, Eu) were prepared by using a combustion technique. The bulky
      powders doped with concentrations corresponding to nano-powders were obtained by
      annealing the nano-powders at high temperature. The emission spectra, XRD spectra
      and TEM were used in the present study. The concentration quenching of
      luminescent centers and energy transfer between luminescent centers in Y2O3 : Ln
      nanocrystal powders were investigated. It was found that the behaviors of
      luminescence concentration quenching for 5D4 --> 7F5 : Tb3+ and 5D0 --> 7F2 :
      Eu3+ in nano-powders are similar to that in bulky powders. On the contrary, the
      quenching concentrations for 5D3 --> 7F5 : Tb3+ and 1D2 --> 3H4 : Tm3+ are
      distinctly higher than that in bulk powders. This owes to the size confinement
      effect: the interface of nanocrystal particles can stop a portion of the energy
      transfer, which happens in the bulk ones, between luminescent centers. The size
      confinement effect can bring different influences to the different types of
      energy transfer. For instance, it will restrain the energy transfer (governed by
      electric dipole-dipole interaction) between the ions in long distances, and will
      hardly affect the energy transfer (governed by exchange interaction) between the
      ions locating at near intervals.

PMID- 19385226
TI  - [Characteristic vibration analysis of M-RNA nucleic acid bases complexes (M = Ca+
      and Mg+) by DFT].
AB  - A density functional investigation of the interaction between calcium and
      magnesium univalent cations and RNA pyrimidine base (cytosine, thymine and
      uracil) was performed to determine geometric coordinates and free energies for
      all possible stable isomers at B3LYP/6-311 + G (2df, 2p) level. The most stable
      isomers C1M, T1M and U1M (M = Ca+ and Mg+) with the lowest free energy among the
      same pyrimidine base tautomers were calculated to determine the characters of
      infrared vibrations. According to the results, two characteristic infrared
      vibrations at wave numbers 1,684 and 1,765 cm(-1) were found for single
      pyrimidine base C1, at 1,747 and 1,792 cm(-1) for T1, 1,763 and at 1,796 cm(-1)
      for U1. In addition, spectrum shifts were found when the cations interact with
      the pyrimidine base tautomers. For deeper analysis, we found that when the stable
      complexes are formed, the cations are prone to act on the oxygen atoms, and cause
      the vibrational frequencies to change, the spectral lines belonging to the
      vibration of C--O--M turn out to redshift and the others turn out to blueshift.
      When the stable complex C1M is formed, the characteristic infrared vibration at
      1,684 cm(-1) mainly caused by the ring's vibration turns out to blueshift about
      10 cm(-1), and the another characteristic vibration of 1,765 cm(-1) caused by
      vibration of bond C--O with oxygen atom acting on cations directly turns out to
      redshift by 112 cm(-1) for complex C1Ca+ and by 110 cm(-1) for C1Mg+. When the
      stable complexes T1M are formed, the characteristic vibration of bond C--O--M
      turns out to redshift about 130 cm(-1) and the vibration of bond C--O turns out
      to blueshift about 55 cm(-1). When the stable complexes U1M are formed, the
      vibration of bond C--O--M turns out to redshift about 90 cm(-1) and about 50 cm(
      1) for another C--O. The characteristic infrared vibration frequencies are
      changed obviously when tautomers act on the cations, which is mainly because
      cations take part in molecule's vibrations and change the force constants and
      reduced masses.

PMID- 19385228
TI  - [Study on synthesis, structure characterization and fluorescence of europium
      complexes of 2-(4-fluorobenzoyl) benzoic acid].
AB  - The present paper reports three new europium complexes, EuL3(H2O)6,
      EuL3Phen(H2O)4 and EuL3 (TPPO) (H2O)5, synthesized with Eu(NO3)3 x 6H2O, 2-(4
      fluorobenzoyl) benzoic acid, Phen and TPPO(L = 2-(4-fluorobenzoyl) benzoic acid,
      Phen = 1, 10-phenanthroline, TPPO = triphenyl phosphine oxide). Their composition
      and chemical structures were characterized by elemental analysis, IR and 1H NMR
      spectroscopy. The IR spectra indicated that all complexes exhibited the
      characteristic peaks of carboxylate, asymmetric stretching vibration (vas (CO2(-
      and symmetric stretching vibration (vs (CO2(- peaks; the C = O stretching band at
      1,692 cm(-1) of COOH and the O--H stretching band around 2,500-3,200 cm(-1)
      disappeared. All these complexes had a smaller Deltav(vas (CO2(-))-vs(CO2(- value
      than that of NaL, so the carboxylate groups coordinated with the europium ion in
      the form of bridging bidentate. In 1HNMR, the signals of hydrogen in 2-(4
      fluorobenzoyl) benzoic acid became wide and shifted upfield, and those in Phen,
      TPPO shifted downfield. The excitation and emission spectra were recorded at room
      temperature. The excitation spectra showed that the optimum excitation peaks of
      these three complexes, EuL3 (H2O)6, EuL3Phen(H2O)5 and EuL3(TPPO)(H2O)5, were at
      353.0, 355.0 and 357.0 nm, respectively. All these three complexes showed Eu3+
      ion characteristic emission bands, the electron-dipole transition 5D0 --> 7F2 and
      magnetism dipole transition 5D0 --> 7F1; their emission peaks were at 596.0,
      617.0; 596.0, 619.0; 595.0, 620.0 nm, and the relative intensities were 1.1, 8.6;
      15.2, 100.0; 3.6, 23.2, respectively. The intensity of 5D0 --> 7F2 was stronger
      than that of 5D0 --> F1, which indicated that europium ions were at asymmetric
      center. The emission intensities of europium ions were greatly sensitized by
      Phen.

PMID- 19385229
TI  - [Fluorescence peak shift corresponding to high chlorophyll concentrations in
      inland water].
AB  - Hyperspectral remote sensing offers the potential to detect water quality
      variables such as Chl-a by using narrow spectral channels of less than 10 nm,
      which could otherwise be masked by broadband satellites such as Landsat TM.
      Fluorescence peak of the red region is very important for the remote sensing of
      inland and coastal waters, which is unique to phytoplankton Chl-a that takes
      place in this region. Based on in situ water sampling and field spectral
      measurement from 2004 to 2006 in Nanhu Lake, the features of the spectral
      reflectance were analyzed in detail with peak position shift. The results showed:
      An exponential fitting model, peak position = a(Chl-a)b, was developed between
      chlorophyll-a concentration and fluorescence peak shift, where a varies between
      686.11 and 686.29, while b between 0.0062 and 0.0065. It was found that the
      better the spectral resolution, the higher the precision of the model. Except
      that, the average of peak shift showed a high correlation with the average of
      different Chl-a grades, and the determination coefficient (R2) was higher than
      0.81. It contributed significantly to the increase in the accuracy of the
      derivation of chlorophyll values from remote sensing data in Nanhu Lake. There is
      satisfactory correspondence between hyperspectral models and chl-a concentration,
      therefore, it is possible to monitor the water quality of Nanhu lake throngh the
      hyperspetral remote sensing data.

PMID- 19385230
TI  - [Research on DNA fluorescence capillary biosensor marked by Goldview].
AB  - Goldview marked DNA fluorescence capillary biosensor was studied in the present
      paper. Based on fluorescence capillary analysis (FCA), the DNA biosensor uses
      capillary as immobilization carrier and detection carrier of DNA probe. Probes
      (20-mer-ssDNA) were immobilized on the inner wall of capillary by poly-l-lysine,
      and DNA fluorescence capillary biosensor (DNA-FCB) was made. After being
      hybridized with complementary target DNA and dyed by Goldview, the target DNA was
      qualified or quantified by detecting the fluorescence density of the Goldview
      using F-4500 spectrofluorometer. The sample volume was 12 microL. The
      concentration of the target DNA showed good linearity with the fluorescence
      intensity in the range of 0. 4-4 micromol x L(-1) (2.4-24 mg x L(-1)) (y =
      65.911x + 3.9944, r = 0.9989). The RSD was lower than 3.5%. The concentration
      detection limit of the target DNA was 0.39 micromol x L(-1) (2.2 mg x L(-1)). The
      DNA-FCB can be used to qualify or quantify the target DNA. It's advantages are
      simplicity of manipulation, thimbleful of sample and reagent volumes, repeated
      use of capillary, and the lowest test cost. By using DNA-FCB to qualify the
      target DNA, we can consumedly decrease the pollution of the environment.

PMID- 19385231
TI  - [Quantum chemistry study on fluorescence spectra of three aromatic hydrocarbons].
AB  - In the present paper, the fluorescence spectra of three common pesticides,
      isoprocarb, metolcarb and pirimicarb, were theoretically studied. The geometries
      of these compounds were fully optimized by density function theory (DFT) method
      at the B3LYP/6-31+G level. The three compounds under study were confirmed as true
      minima on the potential energy surface in the presence of only real frequencies
      by the vibrational analysis. The fluorescence spectra were calculated by
      configuration interaction (CI) method with PCM model, and the results match with
      the experimental values. The results of calculation suggest that the three
      compounds with planar structures are hyperconjugation systems. By the addition of
      the donor-electron groups, the wavelengths of the fluorescence spectra increased,
      and the frequencies underwent red-shift. In addition, the substitute alkyl has no
      more influence on the fluorescence spectra, but the addition of amido groups has
      more influence on the fluorescence spectra.

PMID- 19385232
TI  - [Synthesis and fluorescence properties of thermo-responsive microgel
      nanoparticles].
AB  - In the present paper, the preparation and properties of Eu(III) on poly(N
      isopropylacrylamide-co-acrylic acid) (P(NIPAM-co-AAc)) were described. At first,
      P(NIPAM-co-AAc) microgel nanoparticles were prepared by the precipitation
      copolymerization of N-isopropylacrylamide with acrylic acid in the presence of N,
      N-methylenebisacrylamide in water. The morphology and size of the P(NIPAM-co-AAc)
      nanoparticles were characterized by the scanning electron microscope (SEM)
      method. The result of SEM shows that the sample is uniformly sized spherical
      particle and the average particle size of the P(NIPAM-co-AAc) is about 365 nm.
      Then, EuCl3 was chosen to interact with P(NIPAM-co-AAc) nanoparticles and formed
      the complex of P(NIPAM-co-AAc)-Eu(III). The complex was characterized by Fourier
      transform infrared spectroscopy, ultraviolet-visible and fluorescence
      spectroscopy. It was found that the complex shows thermo-responsive fluorescence
      from the experimental results. There exists a energy transfer between the polymer
      ligand and the Eu(III), which can enhance fluorescence emission of the polymer
      ligand and Eu(III) at the same time. The LCST of P(NIPAM-co-AAc) containing
      Eu(III) has changed little after the formation of the complex of P(NIPAM-co-AAc)
      Eu(III). Therefore, the complex can be used for developing the new applications
      in biomedical and fluorescence field.

PMID- 19385233
TI  - [Influence of introducing hexyloxy group on fluorescence property of 4
      nitrostilbene compounds].
AB  - Two new stilbene derivatives, 4-methacryloxyl-4'-nitrostilbene (NS) and 4-(6
      methacryloxyl)-hexyloxy-4'-nitrostilbene (HNS), were synthesized and
      characterized by FTIR, UV-Vis, HPLC and 1H NMR. The influence of structure,
      concentration and solvent polarity on the fluorescence of the two compounds was
      investigated in the present paper. Results showed that both NS and HNS have
      concentration quenching effect and the fluorescence spectrum exhibited a red
      shift with the increase in the polarity of solvents. Moreover, the donor-acceptor
      structure is formed in HNS due to the introduction of donor group hexyloxy, which
      leads to a 72 nm red shift of the maximum wavelength of fluorescence compared
      with NS, and the fluorescence generated from such composite in DMF solution would
      change from yellow to orange.

PMID- 19385234
TI  - [Fluorescence studies of Eu ions adsorption on pseudo-boehmite colloidal particle
      surface].
AB  - Stable pseudo-boehmite sol was obtained by adding HNO3 as peptizing agent and
      adjusting pH to be 2.0. TEM result shows that the AlOOH colloidal particle size
      is about 60 nm. Field emission transmission electron microscope (FETEM) result
      shows that pseudo-boehmite colloidal particle is composed of 8 nm scaled AlOOH
      nanocrystals. The interaction of Eu3+ ions and colloidal AlOOH nanoparticle was
      investigated. The adsorption of Eu3+ ions on the surface of AlOOH nanocrystal was
      attributed to the chemical adsorption caused by electrostatic attraction. The
      photoluminescence characters of Eu3+ in AlOOH/Eu(NO3)3 composite sol system were
      investigated. The 529 nm emission intensity of Eu3+, I592, decreased with the
      increase in the molar ratio of AlOOH and Eu3+, RBoe/Re. The adsorption ratio
      (denoted R) and the adsorption density (denoted D) of Eu3+ ions on AlOOH
      colloidal particle surface was calculated from I592. The results show that the
      values of R and D increase with increasing RBoe/Re.

PMID- 19385235
TI  - [Study on the interaction of hesperidin or icariin with lysozyme by fluorescence
      spectroscopy].
AB  - The interaction of hesperidin (HES) or icariin (ICA) and lysozyme (LYS) was
      studied by fluorescence spectroscopy in physiological buffer solution. It was
      observed that there was a strong fluorescence quenching effect of hesperidin or
      icariin on lysozyme. The quenching constants of the drugs with lysozyme were
      measured at different temperatures, and the quenching mechanism was suggested as
      dynamic quenching for HES-LYS system and both static and dynamic quenching for
      ICA-LYS system. The thermodynamic parameters of the interaction of hesperidin or
      icariin and lysozyme were measured according to the Van's Hoff equation: the
      enthalpy change (DeltaH) and the entropy change (DeltaS) of HES-LYS system and
      ICA-LYS system were calculated to be 20.29 kJ x mol(-1) and 146.28 J x mol(-1) x
      K(-1), and -3.47 kJ x mol(-1) and 81.16 J x mol(-1) x K(-1), respectively, which
      indicated that the interaction of hesperidin and lysozyme was driven mainly by
      hydrophobic force, whereas the interaction of icariin and lysozyme was driven
      mainly by electrostatic force. It was showed that the reaCtion processes of the
      two systems occurred spontaneously since Gibbs free energy change (DeltaG) values
      were negative. The binding distances of hesperidin and icariin from the lysozyme
      tryptophan residue were calculated to be 1.34 nm and 1.24 nm, respectively, based
      on the Forster's theory of non-radiation energy transfer. The results of
      synchronous fluorescence spectra showed that the binding of hesperidin or icariin
      to lysozyme induced conformational changes in lysozyme.

PMID- 19385236
TI  - [Fluorescence characteristics and analytical application of Mn(II)-piperine
      cetyltrimethylammonium bromide ternary system].
AB  - The fluorescence characteristics of the complex of piperine with cation in
      micellar system were studied. At the same time, the influence of experimental
      condition on the fluorescence intensity was also studied. The experiments
      indicated that piperine had very low fluorescence signal itself. But in pH 8.77
      Na2 HPO4-NaH2PO4 buffer solution, both Mn(II) and cationic surfactant
      cetyltrimethylammonium bromide can enhance the fluorescence intensity and
      stability of piperine. Based on this, a sensitive method has been developed for
      the quantitative determination of piperine in Mn(II)-piperine
      cetyltrimethylammonium bromide ternary system. Under the optimum conditions,
      there is a linear relationship between the enhancement of fluorescence intensity
      and the concentration of Mn(II). The optimal conditions are as follows: the
      concentration of Mn(II) is 2.5 x 10(-4) mol x L(-1) and the concentration of
      cetyltrimethylammonium bromide is 5 x 10(-4) mol x L(-1). The fluorescence
      intensity was determined by a 1 cm quartz cell with the excitation wavelength of
      352 nm and the emission wavelength of 452 nm. The linear range of concentration
      of piperine was 2.02-10.1 microg x mL(-1) with the relative coefficient of 0.9985
      and the detection limit of 0.0602 microg x mL(-1). The relative standard
      deviation (RSD) was 1.10%. The proposed method has been successfully applied to
      the quantitative determination of piperine in the Mongolian medicine Piper longum
      L, and the recovery was within the range of 97.6%-102.0%. The results were very
      satisfactory.

PMID- 19385237
TI  - [Fluorescence spectra of ponceau-4R].
AB  - The fluorescence spectra of ponceau 4R induced by 220-400 nm light were studied
      in the present paper. The result shows that ponceau 4R has four obvious
      fluorescence spectral peaks respectively located at 420, 530, 635 and 687 nm,
      each of these fluorescence spectral peaks has different best induced light, and
      the corresponding fluorescence spectra were listed. It was considered that this
      fluorescence comes from the transition n --> pi* of n electrons in the -OH and
      pi* --> pi of pi electrons in the naphthalene. The fluorescence spectral peaks at
      420 nm come from the transition n --> pi* and the other three fluorescence
      spectral peaks come from pi* --> pi. But the intensity of the four fluorescence
      spectral peaks changes differently with the excited wavelength This paper
      attempted to give the expression of the four fluorescence spectral peaks based on
      the microcosmic mechanism. The reason for that ponceau 4R has complex
      fluorescence characteristic is that ponceau 4R not only has big and conjugate
      structure such as naphthalene and provides electron group -OH which can intensify
      its ability to emit fluorescence, but also absorbs electron group such as N=N
      which can depress its ability to emit fluorescence. Investigation on the
      fluorescence spectra and its characteristics will contribute to the study on the
      fluorescence spectra of other azo pigment and help find a new way for checking
      food safety.

PMID- 19385238
TI  - [Study of retrieving formaldehyde with differential optical absorption
      spectroscopy].
AB  - The present paper introduces the method of retrieving the concentration of HCHO
      with differential optical absorption spectroscopy (DOAS). The authors measured
      ambient HCHO in Beijing region with the help of differential optical absorption
      spectroscopy instrument made by ourself, and discussed numerous factors in
      retrieving the concentration of HCHO with differential optical absorption
      spectroscopy (DOAS), especially, the choice of HCHO wave band, how to avoid
      absorption of ambient SO2, NO2 and O3, and the influence of the Xenon lamp
      spectrum structure on the absorption of ambient HCHO. The authors achieved the
      HCHO concentration by simultaneously retrieving the concentrations of HCHO, SO2,
      NO2 and O3 with non-linear least square fitting method, avoiding the effect of
      choosing narrow wave of HCHO and the residual of SO2, NO2, O3 and the Xenon lamp
      spectrum structure in retrieving process to attain the concentration of HCHO,
      Finally the authors analyzed the origin of error in retrieving the concentration
      of HCHO with differential optical absorption spectroscopy (DOAS), and the total
      error is within 13.7% in this method.

PMID- 19385239
TI  - [Decomposing total suspended particle absorption based on the spectral
      correlation relationship].
AB  - A model for estimating the contributions of phytoplankton and nonalgal particles
      to the total particulate absorption coefficient was developed based on their
      separate spectral relationships, and a constrained nonlinear optimization code
      was used to realize the spectral decomposition. The spectral absorption of total
      particulate matter including phytoplankton and nonalgal particles was measured
      using the filter-pad method during two cruises in autumn in Northern South China
      Sea. Using the dataset collected in 2004, the spectral relationships of particle
      absorption coefficients were examined and the results showed that the
      phytoplankton absorption coefficients at various wavebands could be well
      expressed by aph (443) as the second-order quadratic equations; and the nonalgal
      particle absorption (aNAP(lambda)) could be successfully modeled with the simple
      exponential function. Based on these spectral relationships, we developed this
      partition model. The model was tested using the independently measured absorption
      by phytoplankton and nonalgal materials which were obtained in 2005 from the same
      area. The test results showed that the computed spectral absorption coefficients
      of phytoplankton and nonalgal particles were consistent with in situ measurement.
      Good correlations were fo und between the comput ed phytoplankton absorption
      coefficient and the measured value,with the determination coefficients (r2) being
      higher than 0.97 and slopes being around 1.0; and the RMSE values could be
      controlled within 17% over the main absorption wavebands such as 443, 490 and 683
      nm. Compared with the other two existing models from Bricaud et al. and
      Oubelkheir et al., this method shows many advantages for local applications.
      Moreover, this model does not need any information about pigment concentrations
      and the selected spectral bands are consistent with the ocean color satellite
      sensor. This method could also be used in the total absorption coefficient
      decomposition which provides much insight into the phytoplankton absorption
      retrieval from in situ measurement and ocean color remote sensing data.

PMID- 19385240
TI  - [Kinetic study on the in situ synthesis of nickle phthalocyanine in silica gel
      glass matrix by UV/Vis absorption spectra].
AB  - In decades, metallo-phthalocyanines (MPcs) have undergone a renaissance because
      of their singular and unconventional physical properties. However, for the
      successful application of MPcs in practical devices, it is important to disperse
      MPc molecules into solid state matrix to fabricate MPc doped composite with
      desired properties. Inorganic glass is an ideal matrix because of its
      transparency and high environmental stability. One attractive approach to
      fabricating MPc/inorganic composite is sol-gel technique. In the present paper,
      silica gel glass matrix was prepared by hydrolysis and poly-condensation of
      tetraethyloxysilane. 1,2-dicyanobenzene and analytically pure soluble nickle salt
      were used as the nickle phthalocyanine (NiPc) reactants and chemical synthesis
      technique was used to prepare NiPc doped sol-gel materials at several
      temperatures. During the heat treatment, four 1, 2-dicyanobenzene molecules and
      one nickle ion collide to form a NiPc molecule. In-situ synthesizing process of
      NiPc in the pores of silica gel glass matrix was traced by UV/Vis absorption
      spectra. Owing to the remarkable absorption band of NiPc in visible region,
      quantity of in-situ synthesized NiPc was calculated by the absorbance at certain
      wavelength of 670 nm, using composites with physically doped NiPc as a reference.
      The in-situ synthesized kinetics was studied in detail and found to be consistent
      with Avrami-Erofeev equation The reaction grades were deduced to be 4.5, 4.5,
      3.7, 3.2 and 1.9 respectively at temperatures of 180 degrees C, 185 degrees C,
      190 degrees C, 195 degrees C and 200 degrees C, respectively.

PMID- 19385241
TI  - [Comparative study on selenium and amino acids content in leaves of planted and
      wild Scutellaria baicalensis].
AB  - Scutellaria baicalensis is one of the most important Chinese herbs. It is widely
      used in Asian medicine to improve impaired brain function and to treat headaches,
      and used to treat prostate cancer. It is also known to be anti-inflammatory and
      antifungal, and also seems to have antiviral properties, including possible
      effectiveness against HIV. Scutellaria baicalensis tea and other products are in
      development. In the present study, the content of selenium (Se) in leaves of
      planted and wild Scutellaria baicalensis was determined by fluorescence
      photometer. The contents of 18 kinds of amino acids in the leaves of planted and
      wild Scutellaria baicalensis were determined with amino acids instruments. The
      results showed that the two kinds of leaves were rich in Se content, and the
      content of Se in planted Scutellaria baicalensis (0.051 microg x g(-1)) was not
      significantly different from that in wild one (0.051 microg x g(-1), alpha =
      0.05). The amino acids, of which the total content was up to 14.62% and 10.25%
      separately, were rich in both planted and wild Scutellaria baicalensis. Among the
      18 kinds of amino acids, aspartic acid, glutamic acid and leucine were
      comparatively high in leaves of planted and wild Scutellaria baicalensis. There
      are 8 kinds of amino acids essential to human body, which were higher in leaves
      of planted Scutellaria baicalensis than those of wild one. This study, for the
      first time, determined Se and amino acids content in Scutellaria baicalensis and
      concluded that the leaves of planted type have Se and amino acids content not
      lower or higher than that of wild type, and the planted type could be a good
      substitute of wild type in the development of Scutellaria baicalensis products.
      This study also provided useful data for explaining the multifunction of
      Scutellaria baicalensis and theological basis for developing its medical and
      edible value.

PMID- 19385242
TI  - [Immune resonance scattering spectral analysis of fenvalerate].
AB  - In the pH 7.2 Na2HPO4-NaH2PO4 buffer solutions and in the presence of PEG-6000,
      fenvalerate (Fen) antisera was combined with Fen specifically, and aggregated to
      form immune complex particles that exhibited five resonance scattering peaks at
      350, 390, 420, 440 and 480 nm respectively. The peak at 390 nm was the strongest
      and was chosen for use. Fen concentration (c) in the range of 0.20 to 6.40 microg
      x mL(-1) was proportional to the resonance scattering intensity at 390 nm. Its
      regression equation was DeltaIRS 23.05c-1.39, the correlation coefficient was
      0.9978, and the detection limit was 0.07 microg x mL(-1). Effects of buffer
      solution type, pH value, buffer solution volume, fenvalerate antisera
      concentration, PEG-6000 concentration, incubation temperature and time on the
      resonance scattering intensity were considered in detail. With pH (5.8-8.0)
      increasing, the IRS and Ib all decreased. When the pH value was at 7.2, the
      DeltaIRS was bigger. Three buffer solutions of pH 7.2, including Na2HPO4-citric
      acid, Na2HPO4-KH2PO4 and Na2HPO4-NaH2PO4, were examined. The pH 7.2 Na2HPO4
      NaH2PO4 buffer solution gives the biggest DeltaIRS value. PEG-6000 could enhance
      the DeltaIRS value. When the concentration of PEG-6000 was 50.0 mg x mL(-1), the
      DeltaIRS was achieved at max. Fen was a stable chemical. The IRS increased within
      20 min,while the DeltaIRS remained constant when incubation time was in the range
      of 20-40 min. The condition of a pH 7.2 Na2HPO4-NaH2PO4 buffer solution-50.0 mg x
      mL(-1) PEG-6000-6.67 microg x mL(-1) Fen antisera-30 degrees C-incubation time 20
      min was chosen. According to the procedure, the influence of foreign substances
      on the determination of 1.60 microg x mL(-1) Fen was examined, within a relative
      error of +/- 5%. Results showed that the following coexistent substances had no
      impact on the RS assay: 96 microg x mL(-1) ametryne, 96 microg x mL(-1) m
      aminotoluene, 48 microg x mL(-1) simetryne, 48 microg x mL(-1) p-aminotoluene,80
      microg x mL(-1) BSA, 80 microg x mL(-1) HSA, 80 microg x mL(-1) Fe3+, 80 microg x
      mL(-1) Mg2+, 160 microg x mL(-1) Ca2+, and 160 microg x mL(-1) glucose. The
      results indicated that this RSS assay has good selectivity. This immune resonance
      scattering spectral assay was applied to the determination of Fen in waste water
      samples with satisfactory results. The recovery was in the range of 92.91%
      101.25%, and the relative standard deviation was in the range of 1.71%-4.80%.

PMID- 19385243
TI  - [Research on particle size and size distribution of nanocrystals in urines by
      laser light scattering method].
AB  - In the present paper laser light scattering method was used to investigate the
      particle size and size distribution of nanoparticles simultaneously in urines of
      lithogenic patients and healthy persons. This method is economic, rapid, accurate
      and easy to operate. The results showed that healthy urines are more stable than
      lithogenic urines. In urines of healthy human, the ultrafine crystals were well
      scattered and not aggregated with a smaller size. However, the ultrafine crystals
      in lithogenic urine have a broad size distribution, which increases the
      aggregation trend of nanocrystals. Based on the intensity-autocorrelation curve,
      the stability of urine samples of both healthy human and lithogenic patients was
      comparatively investigated. The relationship between the measurement results and
      the methods of handling sample was studied. The results show that a stable urine
      sample can be obtained by diluting the urine with a ratio of 20%, then
      centrifuging it at 4,000 round per minute for 15 minutes or filtrating it with
      1.2 microm cellulose acetate filter. The results of laser light scattering method
      are consistent with that obtained by transmission electron microscopy (TEM). The
      reasons for the stability of urines are explained from the points of Van der
      Waals force, urine viscosity, pH value, ionic strength, surface charge and zeta
      potential of the ultrafine crystals, and so on. The results in this paper provide
      a new thought for preventing formation and recurrence of urinary stones.

PMID- 19385244
TI  - [Study on application of multi-spectral image texture to discriminating rice
      categories based on wavelet packet and support vector machine].
AB  - Based on multi-spectral digital image texture feature, a new rapid and
      nondestructive method for discriminating rice categories was put forward. The new
      method combined the advantages of wavelet packet and support vector machine
      (SVM). In the present study, the images which are 1 036 pixels in vertical
      direction by 1,384 pixels in horizontal direction with 24-bit depth were captured
      using a red (R) waveband, near infrared (NIR) waveband and green (G) waveband
      multi-spectral digital imager. The three wavebands of image (red, green and NIR)
      can be composed into one image which contains more information than images
      captured by ordinary digital cameras, and the NIR image can catch more
      information than visible spectrum. NIR waveband images were decomposed to 16
      subbands using three wavelet packet multi-resolution. Because the main feature of
      texture information is concentrated on the middle frequency, the 8 subbands of
      middle frequency were selected to calculate entropy, and the entropy of three
      wavebands of original image was calculated at the same time. Eighty images
      (twenty for each category) were used for calibration set and eighty images
      (twenty for each category) were used as the prediction set. Then the rice
      categories were classified by SVM. The classification rate of rice categories was
      only 93.75% using the entropy of original image, but reached 100% by wavelet
      packet decomposition. The overall results show that the technique combining
      wavelet packet and support vector machine can be efficiently utilized for texture
      recognition of multi-spectra, and is an effective and simple technique for
      discriminating the rice categories. This study also provides a foundation for
      rice grading and other rice industry processing such as quality diction and
      milling degree.

PMID- 19385245
TI  - [Spectroscopic study on the interaction between resveratrol and human serum
      albumin].
AB  - The interaction between resveratrol and human serum albumin (HSA) was studied by
      using fluorescence quenching spectra, synchronous fluorescence spectra and ultra
      violet spectra. The Stern-Volmer curve of the fluorescence quenching of HSA by
      resveratrol indicated that the quenching mechanism between resveratrol and HSA
      was mainly static quenching, with nonradiation energy transfer occurring within
      single molecule. The binding constants (KA) were 2.39 x 10(5) (25 degrees C),
      1.25 x 10(5) (35 degrees C) and 1.10 x 10(5) (45 degrees C), respectively.
      According to the Forster theory of nonradiation energy transfer, the binding
      distances (r) were 3.02 nm (25 degrees C), 3.46 nm (35 degrees C) and 3.79 nm (45
      degrees C), respectively. The thermodynamic parameters showed that the
      interaction between resveratrol and HSA was mainly driven by hydrophobic force.
      Synchronous spectrum was used to investigate the conformational change of HSA.

PMID- 19385246
TI  - [Preliminary study on the function of potteries of Liangzhu Culture].
AB  - Liangzhu Culture is an important late neolithic culture of China, but there are
      different opinions on the function of some potteries of Liangzhu Culture, for
      example vat and Ding. In the present paper, for discussing the function of these
      potteries, the content of Cl, Ca and P of some shard samples of vat and Ding from
      Liangzhu site were analyzed by using EDXRF line scanning technology. The results
      show that the content of element Cl in the outside and inside parts of the bottom
      of vat sample is not different from that of other contemporaneous archaic
      potteries, and that the distribution of element Cl in the outside part of the
      bottom of vat sample is the same as that in the inside part of the bottom, so it
      is concluded that the function of vat from Liangzhu Culture is not related to the
      production or storage of salt, but with regard to the true function of this
      pottery more works remain to be done. The analytical results also show that the
      content of two elements, Ca and P, in the bottom of the other pottery, Ding, is
      obviously higher than that in vat and other contemporaneous archaic potteries,
      and that the content of two elements, Ca and P, in the outside part of the bottom
      of Ding sample is higher than that in the inside part of the bottom. So it is
      concluded that Ding from Liangzhu Culture is a kind of cooking ware and its main
      function is meal cooking.

PMID- 19385247
TI  - [Studies on the reaction of norfloxacin with ovalbumin].
AB  - The interaction between norfloxacin (NRF) and ovalbumin (OVA) was studied by
      fluorescence and absorption spectroscopy. The binding constants and the binding
      sites were measured by fluorescence quenching method. It was found that the
      emission peak of OVA was positioned at 338 nm. When the norfloxacin was added
      into OVA solution gradually, the intensity of 338 nm emission peak of OVA
      decreased obviously and moved towards long wavelength. The experiment
      demonstrated that the higher the temperature, the lower the slopes of quenching
      curves of OVA in the presence of different amounts of NRF. It was confirmed that
      the combination of NRF with OVA is a single static quenching process. With the
      increase in the pH of the solution, the quenching efficiency decreased in the
      binding. From thermodynamic parameters, it can be judged that the binding power
      between OVA and NRF is electrostatic effect and H-bond formation. The UV-Vis
      absorption spectra of OVA in the presence of NRF show that the conformation of
      OVA changed.

PMID- 19385248
TI  - [Application and development of spectroscopy methodologies in the study on non
      covalent interactions].
AB  - Spectrophotometric method is widely used in the structure determination of
      biologic macromolecules and non-covalent interactions study for its convenience
      and speed. In the present paper, spectroscopy methodologies in the study of non
      covalent interactions between small-molecule and biomacromolecule is
      comprehensively reviewed with 25 references. This review article focuses on the
      applications and development of common spectroscopy methodologies in the study of
      non-covalent interactions between small molecule and biomacromolecule,including
      the UV, fluorescence, CD, IR, Raman, resonance light scattering technique and
      SPR. The advantages and disadvantages of spectroscopy methodologies are also
      described. UV-Vis absorption spectrum (UV) method is widely used in the study of
      non-covalent interactions for its convenience and speed. The binding site number,
      the apparent binding constant and the interaction mode of non-covalent
      interactions can be obtained by fluorescence spectrum method. Circular dichroism
      (CD) method is effective way in the study of non-covalent interactions measure.
      Spectroscopy information about protein secondary structure and conformation can
      be acquired by infrared spectrometry (IR) method. Raman spectroscopy method is a
      better way to investigate the conformation change in macromolecules in solution.
      Non-covalent interactions can be measured by surface plasma resonance (SPR)
      method under the natural active condition. X-ray diffraction analysis method is
      better for non-covalent interactions research, but it is difficult to cultivate
      crystalline complex.

PMID- 19385249
TI  - [Effect of charge compensation on emission spectrum of Sr2SiO4 : Dy3+ phosphor].
AB  - The Sr2SiO4 : Dy3+ phosphor was synthesized by the high temperature solid-state
      reaction method in air. Dy2O3 (99.9%), SiO2 (99.9%), SrCO3 (99.9%), Li2CO3
      (99.9%), Na2CO3 (99.9%) and K2CO3 (99.9%) were used as starting materials, and
      the Dy3+ doping concentration was 2 mol%. The emission spectrum was measured by a
      SPEX1404 spectrophotometer, and all the characterization of the phosphors was
      conducted at room temperature. The emission spectrum of Sr2 SiO4 : Dy3+ phosphor
      showed several bands centered at 486, 575 and 665 nm under the 365 nm excitation.
      The effect of Li+, Na+ and K+ on the emission spectra of Sr2SiO4 : Dy3+ phosphor
      was studied. The results show that the location of the emission spectrum of
      Sr2SiO4 : Dy3+ phosphor was not influenced by Li+, Na+ and K+. However, the
      emission spectrum intensity was greatly influenced by Li+, Na+ and K+, and the
      evolvement trend was monotone with different charge compensation, i. e. the
      emission spectrum intensity of Sr2SiO4 : Dy3+ phosphor firstly increased with
      increasing Li+ concentration, then decreased. However the charge compensation
      concentration corresponding to the maximum emission intensity was different with
      different charge compensation, and the concentration is 4, 3 and 3 mol%
      corresponding to Li+, Na+ and K+, respectively. And the theoretical reason for
      the above results was analyzed.

PMID- 19385250
TI  - [Comparative study of minerals and some nutrients in organic celery and
      traditional celery].
AB  - Conventional cultivation pattern, integrated cultivation pattern and organic
      cultivation pattern are three patterns in China, and organic produce from organic
      cultivation pattern is considered the best one in quality and safety. Some
      experiments have been done on the effect of different cultivation patterns on the
      vegetable quality, such as the contents of Vc, total sugar, and dissoluble solid,
      which show the organic cultivation pattern and integrated cultivation pattern
      excel the conventional cultivation pattern, but there are no data that show the
      difference in the contents of mineral elements. In the present study, the
      contents of nutritional elements such as Ca, Mg, K, Zn, Fe and Mn and heavy
      elements such as Cu, Cd and Pb in organic celery and traditional celery were
      analyzed by ICP-OES, and the contents of some nutritional ingradients such as
      water, total soluble solid, soluble sugar and asorbic acid were also
      investigated. The results showed that the contents of K and Zn in organic celery
      were respectively 70.22% and 47.93% higher than that in traditional celery, but
      there was no significant difference in the contents of Ca, Mg and Fe, while the
      content of Mn was 47.24% lower in organic celery (alpha = 0.05). The contents of
      Cu, Cd and Pb showed no significant difference between the two kinds of celery,
      and are lower than the national requirement. The content of water and total
      soluble solid showed no significant difference, whereas the contents of soluble
      sugar and asorbic acid in organic celery were 55.04% and 118.18% higher,
      respectively. The difference in the nutritional ingredients and mineral elements
      and safety status between the two kinds of celery provides academic data for the
      comparison between organic vegetables and traditional ones.

PMID- 19385251
TI  - [Study on testing methods of Al content of polyimide hybrid films with Al2O3].
AB  - The inorganic particles hybrid polyimide films are newly emerging advanced
      materials with excellent corona-resistant and have been widely used in frequency
      control motor. The Al2O3/PI hybrid films with different Al2O3 contents were
      prepared by superfine aluminum power treated by coupling agent and polyamide acid
      (PAA). Qualitative analysis and quantitative analysis on the inorganic content to
      it were conducted using Fourier Transform Infrared Spectroscope (FTIR), X-ray
      photoelectron spectroscopy (XPS), Inductively coupled plasma spectrometry (ICP),
      Gravimetric method, Thermogravimetric Analysis (TG/air atmosphere). It was found
      that FTIR and XPS are good qualitative analysis methods. FTIR is used to
      inference possible components by analyzing the structure of material. The method
      has a lot of advantages such as easily operational, good repeatability, high
      accuracy and so on. XPS is mainly used to get information of elements contained
      in the material, it provides information about the core level binding energies
      and oxidation states of complexes. It can be used to identify the species and
      valence states of elements, measure the relative content of elements. The
      relative standard deviations (RSDs) of XPS and TG are too great to perform
      quantitative analysis, the RSDs of XPS are all above 5.0%, and TG's RSDs are also
      above 2.0%. So they can be only used as semiquantitative analysis methods. On the
      contrary, ICP and Gravimetric method are two excellent quantitative analysis
      methods, their RSDs are all below 1.0%. Moreover Gravimetric method only can be
      used to analyze single inorganic constituent complex material, although its
      measured value is closest approach to theoretical value. ICP is the most accurate
      method and it can be used to analyze multi inorganic components in complex
      material, this method proved to be easily operational, rapid, highly sensitive,
      and accurate, and can be adopted as the method of determining many elements
      simultaneously. So a method was got to analysis of inorganic constituent in
      complex material from the conclusion upward. Firstly, components in complex
      material are defined by using FTIR and XPS as qualitative analysis methods and
      then using the result of XPS as a reference, exactly quantitative analysis of
      inorganic constituent in complex material was performed by using Gravimetric
      method and ICP.

PMID- 19385252
TI  - [Determination of U, Th and Tl in fourteen Chinese traditional medicines by
      microwave digestion-ICP-MS].
AB  - Fourteen Chinese traditional medicines were digested by microwave digestion,
      which are generally applied to treat tumor in clinic, and the contents of U, Th
      and Tl in the fourteen Chinese traditional medicines were determined by
      inductively coupled plasma mass spectrometry (ICP-MS), and the results show that
      the change ranges of the elements contents were: 0.005 153-0.1534 microg x g(-1)
      for U; 0.03501-0.4628 microg x g(-1) for Th; 0.00143-1.600 microg x g(-1) for Tl.
      The contents of U, Th and Tl in the fourteen Chinese traditional medicines were
      low, and not with one accord. The determination results of the fourteen Chinese
      traditional medicines were analyzed by SPSS 11.5, and the results show that there
      were not significant deviations(p>0.05) of the contents of U, Th and Tl between
      the medicine of treating the toxifying disease with poisonous agents and the
      medicines of heat-clearing. The study indicates that inductively coupled plasma
      mass spectrometry (ICP-MS) is a quick, accurate, sensitive method to determine
      the contents of U, Th and Tl in Chinese traditional medicine, and the results of
      this study provide reference data for using Chinese traditional medicine safely
      in clinic and developing Chinese traditional medicine.

PMID- 19385253
TI  - [The characteristic analysis of several mineral contents in Chinese orange
      juice].
AB  - A study was carried out on the contents of mineral elements such as K, Ca, Na,
      and Mg in seven different orange varieties, namely Pineapple orange, Hamlin,
      Trovita, Jincheng, 1,232 Tangor, Olinda Valencia and Delta Valencia, by flame
      atomic absorption spectrometry. The results indicated that the content sequence
      of different nutritional elements was K > Mg > Ca > Na, with a range of 1,233.75
      1,866.23, 77.51-167.15, 49.32-125.29 and 1.22-9.26 mg x L(-1) respectively. The
      range scale of the four elements was largely consistent with the reference value
      of AIJN (Association of the Industry of Juices and Nectars from Fruits and
      Vegetables of the European Union). The samples can be clustered into 2 groups by
      factor analysis, and lower Na content would be the characteristic of the Valencia
      varieties. All these data would offer important information for orange juice
      adulteration determination and quality evaluation.

PMID- 19385254
TI  - [Determination of lithium in the oil field water by flame atomic absorption
      spectrometry].
AB  - Flame atomic absorption spectrometry was applied to the determination of micro
      amount of lithium in the oil field water of certain area. In order to determine
      which method is more appropriate for the determination of lithium content in the
      oil field water, standard curve method and standard addition method were
      compared. The effects of dilution, coexistent ions, and deionizers on the
      determination were studied. For the determination of lithium content in the same
      diluted oil field water samples, there exist obvious differences between the
      results obtained from standard addition method and standard curve method.
      Standard addition method gives results with a larger error, whereas standard
      curve method gives more accurate results. It is difficult to eliminate the
      interferences when the standard addition method is used. The standard curve
      method is found to be more suitable for the determination of micro amount of
      lithium in the oil field water for its accuracy, simplicity, and feasibility.
      When the standard curve method is used, both the determined lithium concentration
      and the recovery change with the dilution extent of the oil field water. In order
      to get an accurate result, the oil field water sample should be diluted to 1/200
      or less. In this case, the recovery by standard addition method ranges from 94.3%
      to 96.9%. When sodium phosphate or sodium chloride is used as the deionizer, the
      recovery by standard addition method ranges from 94.6% to 98.6%, or from 94.2% to
      96.3%. In the determination of lithium content in oil field water, there are
      larger experimental errors without the addition of any deionizer. When the
      concentration of coexistent ions is within an allowed range, the addition of
      sodium phosphate as a deionizer can eliminate the interferences of the coexistent
      ions with the determination of the lithium content. If sodium chloride is used as
      a deionizer, a more accurate result can be obtained when the sodium content in
      the samples is near the sodium content in the standard solutions. In general,
      under suitable experimental conditions, sodium chloride can be used as the
      deionizer for the determination of lithium content in the oil field water.

PMID- 19385255
TI  - [XPS and Raman spectral analysis of nitrogenated tetrahedral amorphous carbon (ta
      C : N) films with different nitrogen content].
AB  - Nitrogenated tetrahedral amorphous carbon (ta-C : N) films were prepared on the
      polished C--Si substrates by introducing highly pure nitrogen gas into the
      cathode region and the depositing chamber synchronously using filtered cathodic
      vacuum arc (FCVA) technology. The nitrogen content in the films was controlled by
      changing the flow rate of nitrogen gas. The configuration of ta-C : N films was
      investigated by means of X-ray photoelectron spectroscopy (XPS) and visible Raman
      spectroscopy. It was shown that the nitrogen content in the films increased from
      0.84 at% to 5.37 at% monotonously when the nitrogen flow rate was varied from 2
      seem to 20 sccm. The peak position of C (1s) core level moved towards higher
      binding energy with the increase in nitrogen content. The shift of C (1s) peak
      position could be ascribed to the chemical bonding between carbon and nitrogen
      atoms even though more three-fold coordinated sp2 configuration as in graphite
      was formed when the films were doped with more nitrogen atoms. Additionally, the
      half width of C(1s) peak gradually was also broadened with increasing nitrogen
      content. In order to discover clearly the changing regularities of the
      microstructure of the films, the XPS C(1s) spectra and Raman spectra were
      deconvoluted using a Gaussian-Lorentzian mixed lineshape. It was shown that the
      tetrahedral hybridization component was still dominant even though the ratio of
      sp2/sp3 obtained from C(1s) spectra rose with the increase in nitrogen content.
      The Raman measurements demonstrated that the G peak position shifted towards
      higher frequency from 1,561 to 1,578 cm(-1) and the ratio of ID/IG also rose with
      the increase in nitrogen content. Both results indicated that the graphitizing
      tendency could occur with the increase in nitrogen content in the films.

PMID- 19385256
TI  - [Effect of urinary pH value on the composition of urinary nanocrystals].
AB  - The effect of urinary pH value on the composition of urinary nanocrystals was
      investigated by X-ray diffraction (XRD) and Fourier transform infrared (FTIR)
      spectroscopy. The differentiation of composition of urinary nanocrystals not only
      occurred between the people with different urinary pH, but also occurred in the
      same person when his or her urinary pH changed. At lower urinary pH (such as
      pH<5.8), most of the urinary components are uric acid, acidic phosphate, calcium
      oxalate etc. However, most of these components are urate, phosphate, magnesium
      ammonium phosphate, calcium oxalate etc at higher urinary pH (such as pH>6.2).
      Combining XRD and FTIR methods, t he compositions o f urinary nanocrystals can b
      edetermined accurately. It is helpful to exploring the cause of urinary stones.

PMID- 19385257
TI  - [Microanalysis study of Co-doped ZnO DMS crystal by SEM and XREDS].
AB  - In the present paper,with CoCl2 x 6H2O used as precursor, Co-doped ZnO diluted
      magnetic semiconductor (DMS) crystals were synthesized by hydrothermal method
      with KOH as mineralizer. The morphology, and the relative content and
      distribution uniformity of the surface and inner Co element of synthesized
      crystals were investigated by scanning electron microscope (SEM) and X-ray energy
      dispersive spectrometry (XREDS), respectively. It was found that Co-doped ZnO
      crystals with different morphology were yielded, while the bigger crystals showed
      polar growth charactertistics, and the Co content in the crystal depended on its
      morphology. The exposed face also changed with crystal morphology. There was more
      Co in bigger crystals than in smaller ones. Moreover, more Co located in +c (10
      11)compared to +c (10 10) exposed face, especially for cone crystals. In
      addition, it was observed that there was a little amount of cobalt oxide cluster
      in inner crystal,and the distribution of Co content was relative uniform in both
      the surface and inner part of the crystal. Cobalt oxide cluster may have effect
      on the magnetic properties of Co-doped ZnO diulted magnetic semiconductor since
      Co2+ possesses magnetic property.

PMID- 19385258
TI  - [Global modeling and analyzing of grating spectrometers].
AB  - A method for globally modeling and analyzing grating spectrometers is put forward
      in the present paper. Different from existing methods which are confined to parts
      of a spectrometer, the method takes a grating spectrometer as four functional
      parts, namely imaging optics, detector, reconstruction and display. Effects of
      each part on spectrum are considered and a global model of the spectrometer is
      developed, accompanied with its transfer function. With the help of the model and
      the transfer function, laws of each part affecting the holistic performance are
      summed up. It is suggested that high quality spectrogram needs enhancing baseband
      response and reducing spurious response, and reconstruction is an effective way.

PMID- 19385259
TI  - Ward sister role under scrutiny.

PMID- 19385260
TI  - Theatre nurse shortages.

PMID- 19385261
TI  - Advanced practice in nursing: from concept to reality.
AB  - This article provides an overview of an advanced practice initiative developed at
      NHS Lanarkshire. The criteria that must be met when determining advanced practice
      roles are discussed, and the management and leadership challenges inherent in
      defining and implementing advanced practice in nursing are explored. The article
      concludes with an outline of future activities in this field.

PMID- 19385262
TI  - Here's looking at you.
AB  - In December 2008, readers of RCN Publishing's eight specialist nursing journals
      were surveyed about their careers and asked for their opinions on the state of
      nursing in the UK. This article examines the responses of readers of Nursing
      Management and compares these with the overall survey results.

PMID- 19385263
TI  - Practice development in healthcare service reform.
AB  - This article examines the proposals contained in health minister Lord Darzi's
      Next Stage Review final report and considers how clinical teams can implement
      them in their everyday practice. While the article acknowledges that clinical
      teams may already meet many of the recommendations in the review, some may have
      insufficient evidence to prove that they have, or are not yet working
      systematically enough to ensure consistently high standards of practice. The
      article provides teams with approaches and tools that enable effective
      developments in practice.

PMID- 19385264
TI  - Patient safety: leading improvement.
AB  - This article explains how leadership, particularly nurse leadership, at all
      levels is central to reducing the number of patient adverse events. It describes
      several ways in which nurses can make ward-level and trust-wide improvements to
      patient safety by influencing trust boards, providing visible leadership, setting
      aims, monitoring progress, driving change and disseminating safety knowledge.

PMID- 19385265
TI  - Part of a community.

PMID- 19385266
TI  - How this doctor thinks.

PMID- 19385267
TI  - Hard case--deviations open to questions.

PMID- 19385268
TI  - Why isn't there a doctor in town? Perspective from rural Arkansas physicians on
      dwindling numbers.

PMID- 19385269
TI  - The home health model: reducing hospitalizations by improving medication
      reconciliation and communication.

PMID- 19385270
TI  - Considering an EMR system?

PMID- 19385271
TI  - Peds PLACE: quality continuing medical education in Arkansas.
AB  - The University of Arkansas for Medical Sciences (UAMS) and Arkansas Children's
      Hospital (ACH) sponsor Peds PLACE (Pediatric Physician Learning and Collaborative
      Education), a telemedicine continuing education program. This study assessed to
      what extent participants were satisfied with Peds PLACE and how to improve it. It
      was found that 95% of the participants agreed that the presentations related to
      their professional needs and 98% that it increased their knowledge. In addition,
      81% evaluated the presentations as some of the best they have attended and 93%
      agreed that the information would translate into professional practice and
      enhance patient care. Comments were positive and correlated with the survey data.
      Participants recommended several ways to improve Peds PLACE.

PMID- 19385272
TI  - Meeting standards, following guidelines. Hospital eliminates routine flash
      sterilization, reduces infection risk. Interview by Alan Joch.

PMID- 19385273
TI  - The industry's take on data standards.

PMID- 19385274
TI  - Integrating your facility's ORs.

PMID- 19385275
TI  - Proper chemical use is everyone's responsibility.

PMID- 19385276
TI  - Millions saved with purchasing coalition.

PMID- 19385277
TI  - The role of infection prevention in pandemic preparedness.

PMID- 19385278
TI  - Canine neoplasia--introductory paper.
AB  - The paper gives a brief introduction to canine oncology, including its
      comparative aspects as basis for recording tumours in the animal kingdom. In an
      abbreviated presentation of the Norwegian Canine Cancer Project for the years
      1990-1998, the data (n=14,401) were divided into age groups, each of two years,
      into different categories of tumours, and into age and gender. As expected,
      cutaneous histiocytoma was the dominant tumour type in both sexes during the two
      first years of life. In the age group 2-3.99 years histiocytoma was still the
      largest group in males, but was surpassed by benign epithelial skin tumours in
      females. After the age of 4 years, benign epithelial skin tumours constituted the
      greatest circumscribed group in males, and mammary tumours in females, although
      the summated other tumours, not explained in this survey, dominated overall in
      males. Maligancies (cancer) were shown in the same way, by corresponding groups
      of gender and age. While mastocytoma was the most common tumour and non-Hodgkin's
      lymphoma the second most common during the two first years of life in females,
      the situation was reversed in males. Later, mammary tumours dominated in females,
      while different tumour types not further specified in this summarized report
      dominated in males, until the end of the age registration (above 14 years).
      Number, sex and location of most common tumours are shown in a tabular outline.
      Comparative aspects between human and dog tumours are considered: mammary and
      testicular neoplasia seemed more frequent in dogs than in humans in Norway, while
      intestinal, pulmonary and prostatic malignancies were less common in dogs. In our
      study, vascular tumours and tumour-like lesions constituted about 3% of the total
      data. As benign vascular tumours are incompletely reported to the human Cancer
      Registry, no dependable comparison may be made, but malignant vascular tumours
      have been on the rise during the last decades in the Norwegian human population,
      more so in men then in women. Finally, the article deals briefly with the
      development of endothelial cells, and the sparse information on causal factors of
      vascular tumours.

PMID- 19385279
TI  - Canine vascular neoplasia--histologic classification and inmunohistochemical
      analysis of 221 tumours and tumour-like lesions.
AB  - A light microscopic evaluation of 221 canine vascular tumours and tumour-like
      lesions, supplemented by immunohistochemistry (von Willebrand Factor, CD31,
      vimentin), revealed a high degree of conformity with similar conditions in
      humans. Four main categories of tumours are reported, i.e. benign types:
      haemangiomas (n=127) and lymphangioma (n=1); tumour-like lesions: papillary
      endothelial hyperplasia (n=8) and vascular ectasias (n=2); neoplasms of
      intermediate malignancy: haemangioendotheliomas (n=27), and the obvious malignant
      form: angiosarcomas (n=57). Further classification showed that all subtypes had
      their human counterparts. Papillary endothelial hyperplasia and arteriovenous and
      venous haemangiomas are described for the first time in dogs. The combination of
      conventional histopathologic methods and immunohistochemistry was in many cases
      very useful diagnostically, the latter technique being in some cases
      indispensable for establishing a definite diagnosis. In general CD31 was the most
      useful marker for tumours originating from endothelial cells, especially for
      poorly differentiated haemangiosarcomas.

PMID- 19385280
TI  - Canine vascular neoplasia--a population-based clinicopathologic study of 439
      tumours and tumour-like lesions in 420 dogs.
AB  - This paper deals with a population-based material collected during the years 1990
      1998, and comprises 439 tumours and tumour-like vascular processes from 420 dogs.
      Anatomic location, age, breed and gender are reported. A distinction is made
      between benign neoplasms, tumours of intermediate malignancy, and obvious
      malignant processes (angiosarcomas). Clinical behaviour, comprising recurrence
      and metastatic disposition, is included. Subclassification is done according to
      criteria used in human oncology. More than one half (242 of 439) occurred in the
      skin, and a great majority of skin processes (223 of 242) represented benign
      tumours or tumour-like lesions. The next most common site of summarised lesions
      was the spleen, with 110 cases, with only 17 processes in this organ being
      defined as benign. Splenic involvement was followed by the liver, with 13 out of
      17 processes being angiosarcomas. Eleven of 12 heart tumours were angiosarcomas.
      A majority of skin haemangiomas was of the cavernous type (108 of 211), and more
      than one half (10 of 14) of the capillary haemangiomas were located on dorsal
      sites of the extremities. The mixed capillary/cavernous haemangiomas had a more
      diffuse distribution, although 20 of 31 were found in the skin of the hind limbs.
      Only one lymphangioma and one case of angiomatosis were observed. Most tumour
      like proliferations were papillary endothelial hyperplasias. Recurrence occurred
      in 17 dogs, some of which had received a primary benign diagnosis. Primary
      metastases were observed in 63 animals, the majority in the spleen and heart.
      Dissemination involved a further 23 cases (22 had angiosarcoma). The male/female
      rate of benign tumours was 0.78, for tumour-like processes 1.83, intermediate
      malignant tumours 1.65, and angiosarcomas 1.60. With few exceptions, there was an
      overweight of all subclassified vascular lesions in animals more than 6 years of
      age.

PMID- 19385281
TI  - Canine vascular neoplasia--a population-based study of prognosis.
AB  - The present study is the first complete presentation of the prognosis of all
      histological types of canine vascular tumours, using population-based data. A
      retrospective, longitudinal, population-based study of 420 dogs was carried out
      in 2001-2002 using updated histologically verified diagnoses of vascular tumours
      and tumour-like lesions recorded in Norwegian Canine Cancer Register (NCCR) 1990
      1998. Data on clinical signs and outcome of the vascular tumour, and causes of
      death, were obtained from dog owners and veterinary practitioners by mailed
      questionnaires. The a priori set inclusion criteria required that both
      questionnaire forms were completed, which was the case for 162 of the 420 dogs
      (39%). A benign tumour was diagnosed in 61%, whereas 15% had a tumour of
      intermediate malignancy and 24% had a malignant one. Survival time was estimated
      by the method of Kaplan-Meier (product limit) survival plot, and the survival
      time for three histological diagnoses was compared by a log-rank test. Hazard
      ratios were estimated by Cox proportional hazards model. A p-value <0.05 was
      considered statistically significant. Median survival time of dogs with malignant
      vascular tumour was < or = one day, and the respective median survival times for
      intermediate malignant and benign types were 101 and > or = 1095 days (P<0.0001).
      The median survival time of dogs with splenic vascular tumours was > or = 1095
      days, 110 days and < or = one day for benign, intermediate malignant and
      malignant tumour forms, respectively (P<0.0001). Since the histological diagnosis
      was made without any knowledge of the outcome, the present study confirms that
      the new histological criteria and methods employed have indeed a prognostic
      value. This is the first time it has been shown that a histopathological
      differentiation of malignant tumours into two well-defined subgroups
      differentiates the survival time correspondingly: dogs with less grave tumour
      diagnoses live 100-110 days longer than dogs with the obvious malignant tumours,
      if surgery alone is the treatment regime.

PMID- 19385282
TI  - Canine neoplasia--population-based incidence of vascular tumours.
AB  - We have identified thirteen breeds that are registered in the Norwegian Canine
      Cancer Register with more than five cases of newly diagnosed, primary vascular
      neoplasia in the period from 1990 to 1998. Incidence rates have been estimated
      for the boxer and the Bernese mountain dog because the population at risk is
      known as a result of the 1992/93-census of the Bernese mountain dog, boxer and
      bichon frise. The boxer had a mean annual incidence rate for all types of
      vascular tumours, for both sexes, of 4.3 cases per 1000 dogs. The sex ratio was
      close to one, and the age group of highest risk was 10-12 years. For vascular
      cancer, the mean annual incidence rate for both sexes was 1.5 cases per 1000
      dogs, and the age group of highest risk was 10-12 years. The mean annual
      incidence rate of vascular tumours for the Bernese mountain dog for both sexes
      was 2.5 cases per 1000 dogs. The male to female incidence ratio was approximately
      1/2. The age group of highest incidence rate was 10-11 years for all types of
      vascular tumours as for the vascular cancer. The mean annual incidence rate for
      malignant tumours for both sexes was 1.0 cases per year per 1000 dogs. For all
      thirteen breeds, the relative risk of all types of vascular tumours has been
      computed ad modum Arnesen. The highest estimated incidence rate of malignant
      vascular tumours per 1000 dogs was found in the boxer (1.5). The flat-coated
      retriever and Bernese mountain dog had 1.0 and 0.9, respectively, and the German
      shepherd had 0.8. The study shows that the German shepherd is not the breed with
      the highest frequency of vascular tumour when the population at risk is taken
      into consideration, although the total number of vascular tumours is highest in
      this breed.

PMID- 19385283
TI  - Roger T. Sherman Lecture. Advances in the management of blunt thoracic aortic
      injury: Parmley to the present.
AB  - This article traces the evolution in management of blunt aortic injury (BAI) over
      the past 50 years from the time of the seminal description from Parmley in 1958.
      There have been major advances in both diagnostics and treatment paradigms with
      very rapid technologic advances occurring over the past decade. For many years,
      conventional aortography was the principle diagnostic tool, but it has been
      replaced by the progression of CT. The widespread adoption of antihypertensive
      therapy has sharply reduced the incidence of aortic rupture before planned
      reconstruction. Many patients with major associated injuries have definitive
      treatment of BAI managed in a delayed fashion with the use of hypertensives,
      which appears to improve outcomes. In the past 5 years, definitive treatment has
      changed with the majority of injuries being treated today with endoluminal stent
      grafts as opposed to open thoracotomy and traditional repair techniques.
      Paraplegia rates have diminished from 8 to 10 per cent down to 1 to 2 per cent in
      association with these therapeutic advances.

PMID- 19385284
TI  - Patients with Cushing's syndrome are care-intensive even in the era of
      laparoscopic adrenalectomy.
AB  - We report outcomes from laparoscopic adrenalectomy (LA) comparing patients with
      Cushing's syndrome with those with other adrenal pathology with respect to length
      of stay (LOS), overall complications, and financial implications. We conducted a
      retrospective review of 80 continuous patients (103 glands) undergoing LA. The
      clinical diagnoses were: hypercortisolism (Cushing' syndrome; n=33),
      hyperaldosteronism (Conn's syndrome; n=20), phaeochromocytoma (n=16), and
      neoplasm (others; n=11). Advanced care in the intermediate or intensive care unit
      was necessary in 27 patients, most frequently in our Cushing's population (16 of
      33 [48%]). Six patients sustained major complications, including death in two
      patients; seven patients sustained minor complications. LOS was longer for
      patients with Cushing's syndrome (mean, 5.5 vs. 3.3 days; P = 0.024).
      Financially, patients with Cushing's syndrome had statistically higher total
      hospital (P = 0.009), advanced care (P = 0.002), and anesthetic costs (P =
      0.005). LA in patients with Cushing's syndrome is associated with longer
      hospitalizations, more frequent major complications, and higher advanced care
      requirements, especially for patients undergoing bilateral adrenalectomy. Minor
      complications were infrequent and median LOS was brief regardless of diagnosis.
      Patients with Cushing's syndrome had higher costs for overall hospital charges,
      advanced care, and anesthesia.

PMID- 19385285
TI  - The changing face of trauma: New Orleans before and after Hurricane Katrina.
AB  - Charity Hospital (CH) was devastated by Hurricane Katrina and remains closed.
      Design and staffing of a new, temporary dedicated trauma hospital relied on data
      from prior experience at CH, updated census information, and a changed trauma
      demographic. The study objective was to analyze the new trauma program and
      evaluate changes in demographics, injury patterns, and outcomes between pre- (PK)
      and post-Katrina (POK) trauma populations. A retrospective review of trauma
      patients' demographics, anatomical variables, and physiological variables 6
      months PK and POK was performed under an approved Institutional Review Board
      protocol. Trauma activation triage criteria between study periods were also
      analyzed. Continuous data comparisons between the two time periods were made with
      Student's t test. Dichotomous data were analyzed using chi2 test. The demographic
      of trauma patients is different in the POK interval, reflecting changes in the
      New Orleans population. Modification of triage criteria by the exclusion of
      mechanism as an activation criterion resulted in an increase of patients with
      higher acuity and Injury Severity Score, lower initial Glasgow Coma Score, and a
      higher proportion of penetrating mechanism. Outcome measures reflect longer
      length of stay (4.4 vs. 6.8 days, P < 0.0001) without a significant difference in
      mortality (6.0 vs 7.5, P = 0.227). Hospital data demonstrates that the POK trauma
      system was stressed by the increased acuity, penetrating injury, and number of
      procedures per patient (1.7 vs. 3.4). Resources should be directed toward
      patients requiring multidisciplinary care by increasing intensive care unit beds
      and operating room capacity. Future resource planning in the recovery phases of
      large-scale natural disasters should take into account these observations.

PMID- 19385286
TI  - Acute adrenal insufficiency may affect outcome in the trauma patient.
AB  - Acute adrenal insufficiency in the trauma patient is underrecognized and the
      impact poorly understood. Our hypothesis was that the identification and
      treatment of acute adrenal insufficiency reduces mortality in trauma patients.
      Institutional Review Board approval for the retrospective review of a prospective
      database from a Level 1 trauma center for 2002 to 2004 was obtained. The study
      population included patients receiving a cosyntropin stimulation test (250
      microg) and/or random cortisol level based on our practice management guideline
      and an intensive care unit stay longer than 24 hours. Demographic, acuity, and
      outcome data were collected. The nonresponders had baseline cortisol levels less
      than 20 microg/dL or poststimulation rise less than 9 microg/dL. Independent t
      tests and chi2 statistics were used. One hundred thirty-seven patients had
      cosyntropin stimulation tests performed. Eighty-two (60%) patients were
      nonresponders of which 66 were treated with hydrocortisone and 16 went untreated
      as a result of the discretion of the attending physician. The 55 (40%) responders
      showed no statistical differences in outcome variables whether or not they
      received hydrocortisone. The untreated adrenal-insufficient patients had
      significantly higher mortality, longer hospital length of stay, intensive care
      unit days, and ventilator-free days. Conclusions were: (1) treatment of acute
      adrenal insufficiency reduces mortality by almost 50 per cent in the trauma
      patient; and (2) acute adrenal insufficiency recognized by low random cortisol
      levels or nonresponse to a stimulation tests should be considered for treatment.

PMID- 19385287
TI  - Elderly patients with pelvic fracture: interventions and outcomes.
AB  - We examined the outcome of elderly trauma patients with pelvic fractures.
      Patients 65 years of age and older (elderly) with pelvic fractures were
      retrospectively compared with patients younger than 65 years with pelvic
      fractures and also with elderly patients without fracture. Over the study period,
      1223 patients sustained a pelvic fracture (younger than 65 years, n=1066, 87.2%;
      elderly, n=157, 12.8%). These patients were also compared with 1770 elderly
      patients with blunt trauma without fracture. Although the pelvic fracture
      patients were equally matched for Injury Severity Score (21.2 +/- 13.4 nonelderly
      vs. 20.5 +/- 13.6 elderly), hospital length of stay was increased in the elderly
      (12.5 +/- 13.1 days vs. 11.5 +/- 14.1 days) and they had a higher mortality rate
      (20.4% [32 of 157] vs. 8.3% 88 of 10661). The elderly without fracture also had a
      higher mortality rate when compared with the younger patients (10.9% [191 of
      1760]; P < 0.03). The elderly were more likely to die from multisystem organ
      failure (25.0% [eight of 32] vs. 10.2% [nine of 88]), whereas the nonelderly
      group was more likely to die from exsanguination (45.5% [40 of 88] younger than
      65 years vs. 21.9% [seven of 32] 65 years or older; P < 0.05). Elderly patients
      with pelvic fracture have worse outcomes than their younger counterparts despite
      aggressive management at a Level I trauma center.

PMID- 19385288
TI  - Elective inguinal hernia repair: a unified informed consent, or who wants to know
      what?
AB  - Informed consent is increasingly being standardized. We sought to evaluate
      variability in the amount and quality of information desired by patients in
      choosing whether to undergo elective surgical hernia repair, a prototypical low-
      to moderate-risk common procedure. Consecutive stable outpatients were asked to
      assume that they were considering hernia repair and interviewed with a standard
      questionnaire that asked them to rate their interest in learning about the
      natural history, pathology, and management of inguinal hernia as well as
      herniorrhaphy complications and postoperative recovery. Ninety-eight consecutive
      patients exhibited substantial interpersonal variability in their level of
      interest in receiving information. Although interest in some types of information
      tended to correlate with interest in other types of information, patients' degree
      of interest in receiving information about anesthesia during the procedure was
      independent of other variables. Education and previous exposure to individuals
      with hernias also affected interest in receiving potentially important
      information before deciding whether to consent to hernia surgery. Patients may
      vary with regard to the information they want to receive when deciding whether to
      consent to an invasive procedure. It may be preferable to individualize the
      consent process to patients' preferences rather than adhering to standardized
      content.

PMID- 19385289
TI  - Repair of massive ventral hernias with the separation of parts technique:
      reversal of the 'lost domain'.
AB  - Massive ventral hernia repairs are sometimes complicated by the "loss of domain".
      The separation of parts hernia repair reverses the loss of domain by increasing
      intra-abdominal volume, but not by elevating the hemidiaphragms into the thoracic
      cavity. Hernia repair in patients with a "loss of abdominal domain" is thought to
      be associated with postoperative pulmonary difficulties. A retrospective chart
      review was performed on 102 patients treated by a single surgeon. The 10 patients
      with matching preoperative and postoperative abdominal CT scans were computer
      analyzed for intra-abdominal volume changes and diaphragm height measurements.
      Postoperative pulmonary complications in these 102 patients were recorded. Intra
      abdominal volume increased after separation of parts hernia repair from 8600 +/-
      2800 mL to 9700 +/- 2700 mL (P = 0.01). Diaphragm height did not statistically
      change. Two of the 102 patients had prolonged intubations, and seven other
      patients were ventilated briefly. The separation of parts technique is able to
      close large ventral hernias without a high incidence of pulmonary complications
      as a result of its ability to expand the abdominal domain without a change in
      diaphragmatic height.

PMID- 19385290
TI  - Transfusion, not just injury severity, leads to posttrauma infection: a matched
      cohort study.
AB  - Blood transfusion has been associated with infection; however, the collinearity
      of injury severity has not been clearly addressed to show a direct relationship.
      Using more rigorous analysis, we aimed to untangle the effect of injury severity
      from transfusion leading to sepsis. We hypothesized that blood transfusion
      independently increases infection in massively transfused versus nontransfused
      patients with matched Injury Severity Scores (ISSs). We performed a matched
      cohort study measuring infection rates in trauma patients receiving massive
      transfusion. Control subjects were contemporaneous patients with matched ISS
      receiving no blood. Infection was defined as intraperitoneal or intrathoracic
      abscesses, pneumonia, urinary tract infection, or bacteremia. Multivariate
      logistic and univariate analysis was completed. Infection rate was 61 per cent in
      44 transfused patients versus 20 per cent in 44 control subjects (P = 0.001).
      Odds of infection were eightfold greater in transfused patients (OR, 7.97; 95%
      CI, 2.3 to 27.5; P < 0.001) independent of ISS, Glasgow Coma Scale, mechanism,
      and age. Infection was most associated with transfusion of packed red blood cells
      (PRBCs), although transfusion of other blood products had strong collinearity
      with PRBCs. Transfused patients had eight times the risk of infection independent
      of ISS; this appears to be the result of PRBC transfusion. Modifying the ratio of
      components in transfusion protocols favoring plasma may cause less infection
      after injury.

PMID- 19385291
TI  - Liver transplantation for iatrogenic porta hepatis transection.
AB  - Iatrogenic porta hepatis transection is a rare but devastating surgical
      complication. There are no systematic studies examining the best treatment
      strategy in patients with this injury. We report two cases of transection of all
      three portal structures, one during an open right adrenalectomy and another
      during a laparoscopic cholecystectomy, both of which were transferred to our
      tertiary care center hours postinjury. Diagnostic imaging and exploration
      revealed nonsalvageable livers, and both patients underwent total hepatectomies
      and portocaval shunting. Donor livers were available 12 to 20 hours after United
      Network for Organ Sharing Status 1 listing and both patients survived their
      postoperative course with 2- and 6-year follow up to date. Two-stage total
      hepatectomy with portocaval shunting followed by liver transplantation should be
      considered for patients presenting with porta hepatis transection.

PMID- 19385292
TI  - Perineal injuries at a large urban trauma center: injury patterns and outcomes.
AB  - The purpose of this study was to describe the characteristics of this unique
      patient population, their clinical presentations, and outcomes. The Los Angeles
      County and University of Southern California Medical Center Trauma Registry was
      used to retrospectively identify patients who sustained perineal injuries.
      Information included gender, age, vital signs, trauma scores, mechanisms of
      injury, studies performed, surgeries performed, and outcomes. Pediatric patients
      and injuries related to obstetric trauma were not included. Sixty-nine patients
      were identified between February 1, 1992 and October 31, 2005. One patient died
      on arrival; 85 per cent (58 of 68) were males, mean age was 30 +/- 12 years, and
      there was a penetrating mechanism in 56 per cent. Vital signs on admission were
      systolic blood pressure 119 +/- 33 mmHg, heart rate 94 +/- 27 beats/minute, and
      respiratory rate 20 +/- 6 breaths/min. Glasgow Coma Scale (GCS) was 13 +/- 3,
      Revised Trauma Score (RTS) was 7.2 +/- 1.5, and Injury Severity Score (ISS) was
      11 +/- 12. CT scan was obtained for 23 (33%) patients. Lower extremity fractures
      were 35 per cent and pelvic fractures 32 per cent. The most common surgery was
      debridement and drainage, diversion with colostomy in five patients (7%). Overall
      mortality was 10 per cent. Mortality group mean scores were: GCS, 6; RTS, 5.74;
      and ISS, 34. The survival group mean scores were: GCS, 14; RTS, 7.7; and ISS, 8.
      There was a statistically significant association between mortality and GCS, RTS,
      and ISS scores (P < 0.001). Most patients with perineal injuries (93%) can be
      managed without colostomy. Associated injuries are not uncommon, particularly
      bony fractures. Mortality is mostly the result of exsanguination related to
      associated injuries.

PMID- 19385293
TI  - The lateral paramedian: revisiting a forgotten incision.
AB  - Incisional hernia is a potential complication of all abdominal incisions and
      still remains a significant problem financially and medically. Presently, there
      is a lack of general consensus among surgeons in regard to the optimal treatment.
      The midline incision is the most common used abdominal incision and it carries a
      high incidence of incisional hernia (up to 15%). The paramedian incision was
      known to lead to a small incidence of incisional hernias. This discussion is
      meant to bring the paramedian incision back to the picture as a hope to decrease
      the incidence of incisional hernia.

PMID- 19385294
TI  - An international fellowship in trauma research and the potential benefits for
      fellows, sponsoring institution, and the global trauma community.
AB  - For over a decade, the Los Angeles County/University of Southern California
      Hospital has supported an international fellowship in trauma that provides
      research experience, education, and opportunity for clinical observation at a
      high-volume American College of Surgeons (ACS) designated Level I trauma center.
      We performed a descriptive study of the design, implementation, and results of an
      international fellowship in trauma and critical care. Fellows from 27 countries
      throughout the world have actively engaged in trauma research at Los Angeles
      County/University of Southern California Hospital. Our program involves intensive
      education and clinical observation components designed to facilitate
      dissemination of evidence-based trauma practices throughout the world by
      graduates. The majority of alumni responding to a survey returned to their
      countries of origin, remaining active in trauma care and research. Motivation for
      participation varied, but former fellows universally rated their experience
      highly and stated they would recommend the program to their colleagues. An
      international research fellowship in trauma and critical care provides foreign
      medical trainees opportunities for exposure to research and evidence-based
      practices at a high-volume trauma center. The program is designed to be
      beneficial to both the participating fellow and sponsoring institution; and is
      constructed to effectively promote improved trauma education and the
      dissemination of quality trauma practices internationally.

PMID- 19385295
TI  - Treatment of hyperinsulinemic hypoglycemia due to diffuse nesidioblastosis in
      adults: a case report.
AB  - An 82-year-old man was admitted to our hospital with a complaint of hypoglycemic
      syncope in the early morning. Insulinoma was suspected, but an abdominal CT
      showed no mass. Abdominal angiography showed a slight stain fed from the splenic
      artery. Arterial stimulation and venous sampling (ASVS) showed an abnormal
      insulin response only from the splenic artery. Under a provisional diagnosis of
      insulinoma, surgical treatment was undertaken. Although no pancreatic masses were
      palpable, we performed a distal pancreatectomy. Subsequently, a pathological
      examination revealed diffuse nesidioblastosis. Reported cases of diffuse
      nesidioblastosis have had common clinical features: postprandial hyperinsulinemic
      hypoglycemia, no abnormal findings in radiological examinations, and the presence
      of the ductulo-insular complex on histological examination. Surgical resection is
      recommended, but the extent of surgery is controversial. Our case had some
      clinical features of insulinoma but was diagnosed as diffuse nesidioblastosis
      according to histopathologic criteria. Because ASVS showed that the pancreatic
      body and tail had a lesion producing insulin abnormally, we performed a distal
      pancreatectomy to cure the hypoglycemia. Clinically, it is very difficult to
      distinguish diffuse nesidioblastosis from insulinoma. When we treat
      hyperinsulinemic hypoglycemia, ASVS can be an essential examination to decide the
      extent of pancreatectomy.

PMID- 19385296
TI  - Carcinosarcoma of the colon: a rare cause of colovesical fistula.
AB  - Carcinosarcomas are relatively rare tumors composed of both carcinomatous and
      sarcomatous components. The most common sites involved by this tumor are the head
      and neck, respiratory tract, uterus, ovaries, and fallopian tubes. Within the
      gastrointestinal tract this tumor most often occurs in the esophagus, followed by
      the stomach. Carcinosarcomas are very aggressive tumors associated with a poor
      prognosis. The first case of carcinosarcoma of the colon was reported in 1986.
      The case reported here is the only one involving an associated colovesical
      fistula.

PMID- 19385297
TI  - Elastofibroma: diagnosis and treatment of six cases.
AB  - Elastofibroma is a rare, benign pseudotumor that arises from connective tissue,
      most commonly found at the right scapular tip. These tumors usually can be
      distinguished from malignant soft-tissue tumors by their anatomical location and
      also through imaging techniques. Although elastofibroma is rare, it is important
      for surgeons to be aware of this diagnosis to prevent unnecessary biopsies and
      unnecessary operations. We report a series of six patients, four of whom were
      female, with a median age of 62.5 years, diagnosed with and treated for
      elastofibroma. Five of the six patients had unilateral lesions, while one patient
      had bilateral elastofibromas. All unilateral lesions were found on the right
      side. The elastofibroma in five of six patients was located on the subscapular
      tip, the remaining patient's elastofibroma was found on the chest wall external
      to the pleural surface. The pathogenesis of this lesion is discussed, as recent
      evidence suggests a neoplastic origin to elastofibroma. Additionally, cellular
      changes occurring in elastofibroma may reflect the pathogenesis of other
      disorders of elastic fibers.

PMID- 19385298
TI  - Compound intussusception in an adult: a rare cause of long standing abdominal
      pain.

PMID- 19385299
TI  - Surgical management for acute cholangitis in patient with a left lobe liver
      lesion.

PMID- 19385300
TI  - Profound hemorrhage in a patient taking herbal products.

PMID- 19385301
TI  - A large adrenal teratoma in a neonate.

PMID- 19385302
TI  - Empyema--a complication of vacuum-assisted closure of infected thoracotomy wounds
      in two consecutive cases.

PMID- 19385303
TI  - Enteric duplication cyst in a 33-year-old man.

PMID- 19385304
TI  - Laparoscopic cholecystectomy in the presence of abdominal situs inversus: does
      surgeon positioning matter?

PMID- 19385305
TI  - Perforated ulcer mimicking a spontaneous pneumothorax in a patient with
      congenital diaphragmatic hernia.

PMID- 19385306
TI  - [The GISSI-HF trial].

PMID- 19385307
TI  - [Heart failure epidemiology in Apulia, Italy, from 2001-2006].
AB  - BACKGROUND: Heart failure is one of the main causes of morbidity and mortality in
      western countries, engaging from 1% to 2% of the healthcare budget in Italy. The
      aim of this study was to evaluate the course of heart failure over time in the
      Apulia region on the basis of the hospitalization analysis. METHODS: Analyses of
      the directional informative system data of the Apulia region, Italy, coming from
      hospital discharge records, allowed the estimation of the overall admission rate
      in Apulia from 2001 to 2006, of admissions for cardiovascular disease and heart
      failure as the main diagnosis, classified according to age, average
      hospitalization rates and of discharge units. RESULTS: In Apulia, overall
      admissions decreased by 8.6% from 2001 to 2006, whereas the costs related to
      hospital admissions increased by 2.41%. Admissions for cardiovascular diseases
      decreased by 0.73% when shock and cardiac failure were excluded, whereas they
      increased by 1.3% when shock and cardiac failure were included. Admissions with
      DRG 127 stepped up by 15.26%; this increase was mainly related to a higher number
      of hospitalizations of patients > 75 years old. From 2001 to 2006, admissions for
      heart failure increased in Cardiology wards, whereas they decreased in coronary
      care units and Medicine wards. CONCLUSIONS: The data related to the increase in
      hospital admissions for heart failure are relevant for their economic and
      organizational impact, landing support to the need for effective patient
      management in order to reduce high early rehospitalization rates.

PMID- 19385308
TI  - [Mitral valve replacement in a patient with severe mitral regurgitation and non
      compaction of the ventricular myocardium].

PMID- 19385310
TI  - Home health help.

PMID- 19385311
TI  - Pressing issues. Congress weighs strategies to expand access to coverage and meet
      the needs of the growing number of uninsured.

PMID- 19385312
TI  - Legislation supports progress in health information technology.

PMID- 19385313
TI  - There's no place like home. Home monitoring devices are popular with patients and
      show promise for improving care and containing costs.

PMID- 19385314
TI  - Closing the gap. Health plans offer training to improve the quality of cross
      cultural care.

PMID- 19385315
TI  - Wellness: collaborations are the key.

PMID- 19385316
TI  - The giving kind. Putting their money where their hearts are, employees deliver on
      charitable dollars.

PMID- 19385317
TI  - Safe & sound. Interview by Helena Gail Rubinstein.

PMID- 19385318
TI  - Increasing consensus with patients and their loved ones.

PMID- 19385319
TI  - Increasing rates of organ donation: exploring the Institute of Medicine's boldest
      recommendation.

PMID- 19385320
TI  - Translating the IOM's "boldest recommendation" into accepted practice.

PMID- 19385321
TI  - Public policy should facilitate organ donation for transplantation: a commentary
      on "Increasing rates of organ donation: exploring the IOM's boldest
      recommendation".

PMID- 19385322
TI  - Ethics consultation and "facilitated" consensus.

PMID- 19385323
TI  - Consensus and independent judgment in clinical ethics: or what can an eighteenth
      century French mathematician teach us about ethics consultation?

PMID- 19385324
TI  - Difficult patients, overmedication, and groupthink.

PMID- 19385325
TI  - Groupthink and caregivers' projections: addressing barriers to empathy.

PMID- 19385326
TI  - A process and format for clinical ethics consultation.

PMID- 19385327
TI  - Seeking excellence in hospital care: evolving toward a systems approach.

PMID- 19385328
TI  - Cell phone and road safety.

PMID- 19385329
TI  - [Fleas (Siphonaptera): a new old infestant in urban environment. Analysis of the
      cases verified in the South Piedmont in the years 2005-2008].
AB  - In the present study, ten cases of human and environmental infestation, observed
      between 2005 and 2008 in the Southern part of Piedmont, are reported. The
      infestation were caused by fleas and in particular by Ctenocephalides felis. The
      importance of human pulicasis transmitted by animals you have with (cats) and
      related risks to human health is inderlined. In the past pulicasis, mainly due to
      Pulex irritans, was related to poor hygienic conditions. On the contrary
      nowadays, pulicasis in urban habitats seems to be caused, on the basis of the
      observed cases, by particular fleas species of low host specificity and to linked
      to the available host species.

PMID- 19385330
TI  - [Measles and its secondary pulmonary complications: prevention is better than
      treatment].
AB  - Recent measles outbreaks observed in North America and in several European
      countries, including Italy, raised the attention about the risks linked to this
      infection and the need of implementing and maintaining adequate preventive
      strategies. Measles may cause several respiratory complications such as chronic
      obstructive lung disease, pneumonia, with subsequent development of chronic
      suppurative lung disease, giant cells pneumonia or progressive respiratory
      insufficiency. The current preventive strategies aim to improve vaccination
      coverage rates with 2 doses of measles-mumps and rubella vaccine, and to catch up
      individuals who have not been previously vaccinated. The present review analyses
      pulmonary complications of measles and measles preventive strategies. Elimination
      of measles is a feasible goal. Since measles complications are preventable by
      vaccination, improvement in vaccination coverage is highly desirable.

PMID- 19385331
TI  - [Acute pancreatitis hospitalization in Veneto Region, Italy].
AB  - The incidence rate of acute pancreatitis (AP) has been reported as having
      increased during recent decades and associated mortality lies around 10%. This
      study was undertaken to establish the current AP hospitalization and mortality
      rates in Veneto Region. A retrospective study of all cases of acute pancreatitis
      admitted in hospital between 2000 and 2007 was carried out in all Veneto
      population. Data concerning patients discharged with a diagnosis of acute
      pancreatitis (ICD 9-CM code: 577.0) were obtained from the Regional data
      warehouse and analysed on a computer database. Altogether 11,685 discharges for
      AP were recorded; median age of the patients was 61.6 +/- 20.3 years. The mean
      annual AP hospitalization rate was 30.6 per 100,000 and in-hospital annual
      mortality rate (death from all causes) was 1.1 per 100,000 population.
      Hospitalization and mortality rates were larger in older and increased sharply
      with age. Hospital admissions for AP rose from 29.3 in 2000 to 32.2 per 100,000
      population in 2007 without significative variations in mortality rate probably
      due to the increase of effectiveness and quality of care. The AP hospitalization
      rate in Veneto population is comparable to what has been found elsewhere in Italy
      and AP remains an increasing disease with high mortality.

PMID- 19385332
TI  - [Factors influencing uptake of influenza vaccination in healthcare workers.
      Findings from a study in a general hospital].
AB  - Despite recommendations, influenza vaccination coverage in health professionals
      remains low throughout the world. In order to identify reasons for adherence or
      refusal we conducted a study within our hospital by means of interview
      questionnaires which were distributed to health care workers to reveal factors
      influencing acceptance or refusal of vaccination and to get suggestions to
      improve vaccination coverage. There is good overlap between our results and data
      obtainable from international literature: the main motivating factor for
      vaccination is personal protection against influenza, while only a significantly
      smaller part gave protection of patients as a reason. The main factors for not
      adhering to vaccination are belief the vaccine is not effective, influenza
      related sick leave, fear of adverse effects and lack of availability. These data
      point out the need for more information concerning the importance of influenza
      infection within risk groups, the safety and effectiveness of the vaccine.
      Further, it is suitable to increase availability of the vaccine free of charge.

PMID- 19385333
TI  - [Epidemiological impact of RV gastroenteritis in the Abruzzo Region: SDO
      analysis].
AB  - RV represent the principle cause of acute gastroenteritis in infants in the
      world. In developing countries they are responsible for a high mortality rate in
      children under the age of five, whereas, in industrialized countries the RV
      infection is mainly related to hospitalisation. In order to study the
      epidemiological impact of enteritis caused by RV, we used the SDO files (hospital
      discharge code) in the Abruzzo Region relative to the years 2003-2006. Of a total
      number of 3146 children under the age of 5 who were diagnosed with
      gastroenteritis at the moment of hospitalisation, 1025 presented gastroenteritis
      of viral origin and 48.4% (496) due to RV. Furthermore, 253 hospital admissions
      were observed for RV in a second diagnosis. Infants of 12-23 months are those
      subject to the highest rate of hospitalisation ranging from 295/100.000 and
      517/100.000. The use of the SDO files can determine an underestimation of the
      hospitalisation incidence for RV because to confirm a correct diagnosis the
      analysis of faeces should be systematically carried out but this is not always
      undertaken. The implementation of a secure and efficient vaccine strategy seems
      to be justified in poor countries, whereas in the industrialized countries, such
      a strategy can reduce the health expenditure for gastroenteritis by RV.

PMID- 19385334
TI  - [Evaluation of environmental pollutant exposure in paediatric age: the case of
      "benzene"].
AB  - The aim of the study was to evaluate benzene exposure in paediatric age. The
      research was conducted among a group of 243 children (5-11 years) residents in
      two areas of Latium, respectively middle urbanization and rural area. Data was
      collected by a questionnaire administered to parents and analytical
      determinations of unmodified benzene, trans,trans-muconic acid and S
      fenilmercapturic acid in urinary samples collected at the end of a "typical day"
      (school day). Comparison of data showed that unmodified benzene is a better
      biomarker of short term exposure, while metabolites are more useful to assess
      long term exposure, therefore integrate approach results fundamental to evaluate
      the intake of low environmental concentrations of benzene. In the present
      research, high significant exposure factors resulted urbanization of area and
      passive smoke exposure in domestic environment. Consequently, prevention programs
      on these specific factors become necessary to reduce benzene health risk for
      general population, especially to protect a particular susceptible group as
      paediatric age.

PMID- 19385335
TI  - [Drivers' random controls and population's recent drug use monitoring].
AB  - Substance abuse, particularly among young people, does not seem to have the
      tendency to decrease. Our knowledges on this phenomenon are manifold and they
      validly compete to address the actions of contrast. Nevertheless, it would seem
      profit to be able to have further informations, to place side by side to those
      already existing, with the aim to improve the surveillance of the phenomenon. For
      this purpose, in the present paper we propose a monitoring model based on the
      results of random controls on road, carried out by the Police (or by the
      Hospital) in relationship to the road safety. The representativeness of the data
      that we could get this way appears elevated as an hight percentage of the
      population own the driver's licence. As it is shown, these controls could be both
      individual and related to drivers' pools of biological samples. This last
      approach would seem to be more practicable since problems relating to the
      drivers' privacy would be avoided.

PMID- 19385336
TI  - [Identification of Legionella spp. by means of cultural and molecular methods in
      a public hospital].
AB  - An epidemiologic study on the isolation of Legionella spp from the sanitary water
      of a public Hospital in Cagliari (Italy) has been performed. The aim of the study
      was the comparison between the isolation of various Legionella spp from different
      hospital sources and the real hazard of Legionella infection of the inpatients.
      Two test methods were used for Legionella detection: a) the culture on selective
      media, that has the disadvantage of being quite time-consuming and of isolating
      also other bacterial species. Furthermore, the culture method often fails the
      isolation of vital but not culturable bacteria (VBNC); b) the PCR molecular
      method, which is rapid and precise and recognizes also VBNC cells. The most
      relevant result of this work was that, in spite of the isolation of a
      considerable number of Legionella spp (even Legionella pneumophila), no case of
      infection was detected in the Hospital during the period of the study.

PMID- 19385337
TI  - [Game as a strategy to educate youngsters about disability].
AB  - Disability is an interesting social topic even if it is sistematically neglected
      in common educational programs that are addressed prevalently to disabled person
      and not to all community. But only a community approach can promote a full social
      inclusion of all its members. Game is an easy and funny method to improve social
      participation and control emotions that this topic can hide. Aim of this article
      is to illustrate how some sensitive and motorial experiences can be easily
      proposed in a young community to explicit educational finalities.

PMID- 19385338
TI  - [Overweight and obesity related risk factors].

PMID- 19385339
TI  - [Somatic diseases of the schizophrenic patient].
AB  - Cardiovascular diseases and metabolic disorders such as obesity, diabetes and
      metabolic syndrome that increase their risk, are common in schizophrenic
      patients. Psychiatric therapy of the schizophrenic patient should from the
      beginning also include examination of somatic status, support towards a healthy
      lifestyle and appropriate treatment of somatic diseases. Psychiatrists should
      update their knowledge of diagnostics of somatic diseases, and other medical
      profession should be aware of the substantial associated somatic morbidity.

PMID- 19385340
TI  - [Thromboembolic complications in day case surgery].
AB  - Prevention of venous thrombosis in surgical hospital patients hasgained attention
      due to the fact that in spite of therapy, deep vein thrombosis and pulmonary
      embolism can cause long-term impediment and even mortality. In day case surgery,
      the threat of venous thrombosis has been considered low and few studies on the
      subject are available. On the other hand, increasingly diseased and aged patients
      are operated on day case surgery basis and more demanding procedures are
      performed for patients being discharged from the hospital during the same day. In
      addition, more information is constantly obtained concerning the significance of
      risk factors.

PMID- 19385341
TI  - [Is diagnosing fibromyalgia necessary?].
AB  - Fibromyalgia is a controversial pain syndrome with chronic widespread pain
      (occurring on both sides of the body as well as axially below and above the
      waist) and unexplained fatigue as the predominating features. Fibromyalgia
      involves lots of symptoms focusing on different organ systems. In sensory
      examination the most significant finding is general allodynia. The widespread
      chronic pain and tender points at certain locations as reported by the patient
      differentiate fibromyalgia patients from those suffering from other diseases of
      the musculoskeletal system.

PMID- 19385342
TI  - [Food additive hypersenisivity--near myth].
AB  - There are over 200 food additives that have been approved in Finland. They are
      being used in order to improve preservability, flavor, appearance and texture.
      Some of them may cause hypersensitivity reactions, the most common being
      anaphylactic reactions, urticaria and exacerbation of asthma. Such reactions are,
      however, very rare. Anaphylactic reactions and other symptoms have resulted from
      carmine, lysozyme, acetic acid and acetates, gums of plant origin, sulfites and
      tartrazine.

PMID- 19385343
TI  - [Treatment of atopic eczema].
AB  - Atopic dermatitis affects 15 to 20% of the populations, the proportion being even
      larger in children. The diagnosis is a clinical one. Essential symptoms include
      itching and eczema on typical regions of the skin, as well as dry skin. The
      prognosis is good, but development of respiratory allergy is common. Instructed
      self-care constitutes the basis of therapy. The skin is inflamed and its care is
      essential. First line treatment comprises regular application of emollient cream
      and intermittent use of ointments containing corticosteroids.

PMID- 19385344
TI  - [Fever from the cold--familial cold autoinflammatory syndrome].
AB  - Familial cold autoinflammatory syndrome (FCAS) is a dominantly inherited syndrome
      caused by mutations of the CIAS1 gene. It is characterized by recurrent episodes
      involving fever, urticaria, articular symptoms and conjunctivitis. The episodes
      may be associated with exposure to cold. In some families, association with
      reactive AA amyloidosis has been described for the syndrome. We describe a
      Finnish family, in which at least 16 persons were affected with FCAS, and one
      person had been diagnosed with renal amyloidosis.

PMID- 19385345
TI  - [Update on current care guidelines. Safe use of non-steroidal anti-inflammatory
      drugs].
AB  - Pain medication should be based on patient's needs and risk profile. Age > 65
      years, prior ulcer, co-morbidities, large daily dose, Helicobacter pylori
      infection, concurrent use of glucocorticoids, serotonin re-uptake inhibitors, or
      warfarin increase the risk of upper gastrointestinal bleeds. As a preventive
      strategy the use of concurrent proton pump inhibitors with non-selective NSAIDs
      is recommended. It is also possible to use COX-2 selective NSAIDs but they are
      contraindicated for persons with atherosclerotic diseases and special
      consideration is required for persons with risk factors of heart diseases.
      Paracetamol is the drug of choice for pain.

PMID- 19385346
TI  - Time to step up to the plate: adopting the WHO 2006 growth curves for US infants.

PMID- 19385347
TI  - Mothers' experiences of sharig breastfeeding or breastmilk co-feeding in
      Australia 1978-2008.
AB  - While the concept of breastfeeding in contemporary Western culture is of a mother
      breastfeeding her own baby or babies, others have replaced the mother as provider
      of breastmilk, for a variety of reasons, through most periods of human existence.
      Existing policies for the sharing of this bodily fluid, milk, appear to have been
      written without the benefit of a detailed examination of the actual experiences
      of the mothers and babies involved. This study attempts to fill this information
      gap by investigating the sharing of breastfeeding or expressed breastmilk by
      Australian women in a recent thirty-year period, 1978-2008. The objective of this
      study was to explore the mothers' experiences of sharing breastfeeding or human
      milk including: the circumstances in which this bodily fluid was freely shared;
      what screening process, if any, was used before the milk of another mother was
      accepted; the mothers' feelings about the experience; the reported attitudes of
      others; and the children's behaviour when put to the breast of someone other than
      the mother. The underpinning reason for the sharing of breastfeeding or
      breastmilk was the desire of mothers to provide human milk to their babies,
      exclusively, including while they were absent or temporarily unable to
      breastfeed. Most mothers were selective about those with whom they would share
      breastfeeding or breastmilk.

PMID- 19385348
TI  - Mothers' experiences with breastfeeding management and support: a quality
      improvement study.
AB  - The purpose of this study was to examine the experiences on mothers with regard
      to the breastfeeding support and management provided by healthcare professionals
      on an acute care postpartum unit in a multiethnic obstetrical referral center in
      Montreal, Canada. The study survey was largely based on the UNICEF/World Health
      Organization's (1998) ten steps to successful breastfeeding. The convenience
      sample included 60 recently-delivered mothers. Findings indicated that
      primiparous women and women who delivered by caesarean section consistently
      received more information about breastfeeding management than multiparous women
      and women who delivered vaginally. However, the study does suggest that all
      women, regardless of parity or type of delivery, have information and support
      needs related to breastfeeding. A total of 29 mothers (67%), who intended to
      breastfeed exclusively, supplemented with artificial baby milk. Of these mothers,
      16 (55%) stated 'milk insufficiency' as their primary reasons for supplementing.
      Overall, respondents perceived healthcare professionals to be encouraging of
      breastfeeding, and 48 mothers (80%) were 'moderately' to 'very' satisfied with
      the breastfeeding education and support received. These findings suggest that
      overall adherence to breastfeeding best practices in the current study hospital
      are below targets set by the World Health Organization for 'Baby Friendly'
      status. Results from the study can be used to target areas for improvement.

PMID- 19385349
TI  - Biofilm removal with a dental water jet.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of a dental
      water jet on plaque biofilm removal using scanning electron microscopy (SEM).
      METHODOLOGY: Eight teeth with advanced aggressive periodontal disease were
      extracted. Ten thin slices were cut from four teeth. Two slices were used as the
      control. Eight were inoculated with saliva and incubated for 4 days. Four slices
      were treated using a standard jet tip, and four slices were treated using an
      orthodontic jet tip. The remaining four teeth were treated with the orthodontic
      jet tip but were not inoculated with saliva to grow new plaque biofilm. All
      experimental teeth were treated using a dental water jet for 3 seconds on medium
      pressure. RESULTS: The standard jet tip removed 99.99% of the salivary (ex vivo)
      biofilm, and the orthodontic jet tip removed 99.84% of the salivary biofilm.
      Observation of the remaining four teeth by the naked eye indicated that the
      orthodontic jet tip removed significant amounts of calcified (in vivo) plaque
      biofilm. This was confirmed by SEM evaluations. CONCLUSION: The Waterpik dental
      water jet (Water Pik, Inc, Fort Collins, CO) can remove both ex vivo and in vivo
      plaque biofilm significantly.

PMID- 19385351
TI  - Time for change: oral health self-care practices based on evidence and behavior
      patterns.

PMID- 19385350
TI  - The dental water jet: a product ahead of its time.
AB  - The dental water jet was invented by Dr. Gerald Moyer, a dentist, and John
      Mattingly, an engineer, in Ft. Collins, Colorado, in the late 1950s. The dental
      water jet, also known as an oral irrigator, was introduced to the dental
      profession in Texas during the 1962 Dallas Dental Convention. Numerous studies
      measuring the irrigator's efficacy in different cohorts have been published in
      peer-reviewed journals. The results of those studies are discussed in this
      article. The bulk of research has been conducted on one product (Waterpik dental
      water jet, Water Pik, Inc, Fort Collins, CO). This article is designed to provide
      dental professionals with the evidence essential to making an informed decision
      on the oral health benefits and expected outcomes of the dental water jet.

PMID- 19385352
TI  - Waterpik dental water jet: creating value for your patients.

PMID- 19385353
TI  - Human trafficking: 21st century slavery.

PMID- 19385354
TI  - Better living through chemistry.

PMID- 19385355
TI  - Going organic.

PMID- 19385356
TI  - The American Recovery and Reinvestment Act of 2009.

PMID- 19385357
TI  - Leg pain in a young soccer player: the diagnosis of acute exertional compartment
      syndrome.

PMID- 19385358
TI  - Informed consent and informed refusal in Oklahoma.

PMID- 19385359
TI  - Introduction: a symposium in seven parts.

PMID- 19385360
TI  - Part one: definition of narrative medicine.

PMID- 19385361
TI  - The $44,000 question.

PMID- 19385362
TI  - Over-prescribing, under-prescribing: who is responsible and what is at risk?

PMID- 19385363
TI  - TMA IIC keeping track of TennCare inequities.

PMID- 19385364
TI  - HIT changes in the economic stimulus package.

PMID- 19385365
TI  - Rx drug safety in TN: some successes, some challenges.

PMID- 19385366
TI  - Teen prescription drug abuse a major health concern.

PMID- 19385367
TI  - Health care spending: how much is "too much"? Part II: personal costs and
      investment.

PMID- 19385368
TI  - Should we settle?

PMID- 19385369
TI  - Speaking for results: how to make presentations with confidence and credibility.

PMID- 19385370
TI  - Aortic thrombosis in infancy.
AB  - A 33-day-old female was admitted to hospital with the diagnosis of viral
      bronchiolitis. The physical examination performed after treatment with
      bronchodilators revealed a grade 2/6 systolic ejection murmur at the left upper
      sternal edge. The arterial pulses and blood pressure in all extremities were
      normal. The two-dimensional echocardiogram revealed a mass measuring 3.5 x 3.5 cm
      at the ductus level consistent with a thrombus; there was flow acceleration at
      the level of the proximal descending aorta with no significant gradient. All
      other laboratory tests were normal except for an elevated platelet count. The
      infant was treated with subcutaneous enoxaparin and oral aspirin for four months
      and nine months, respectively Progressively the clot became smaller, however
      still visible at last evaluation at age of 12 months. Her growth and development
      remained normal. Aorticthrombosis in neonates and young children is uncommon.
      Until 2000 only 63 cases had been reported in the English literature. Spontaneous
      aortic thrombosis is rare. A 20-year literature review in 2006 yielded only 12
      such cases. The clinical presentation is variable and the prognosis can be life
      threatening. The prognosis depends on the size and location of the thrombus, the
      underlying cause, delay in reaching a diagnosis, and the treatment modality.

PMID- 19385371
TI  - Diffuse ST segment elevation: what's your diagnosis? Acute pericarditis.

PMID- 19385372
TI  - Is suicide foreseeable?

PMID- 19385373
TI  - Hansen's disease with HIV: a case of immune reconstitution disease.
AB  - Immune reconstitution inflammatory syndrome (IRIS) is an acute symptomatic
      expression of a latent infection during the recovery of the immune system usually
      as a response to antiretroviral therapy (ART). Opportunistic infections can
      trigger IRIS. Hansen's disease is an infection caused by Mycobacterium leprae (M.
      leprae). There have been a limited number of case reports reporting the
      presentation of the co-infection of HIV and M. leprae. We report an unique case
      of IRIS in a patient co-infected with HIV and M. leprae presenting as an
      exacerbation of his Hansen's Disease where the patient's skin lesions progressed
      from borderline tuberculoid to lepromatous leprosy following ART administration.

PMID- 19385375
TI  - Post-infant circumcision amongst children in Hawai'i.
AB  - BACKGROUND: The purpose of this study is to determine the frequency of
      circumcision in children older than 12 months of age in US born versus non-US
      born children in Hawai'i from 1996-2005. METHODS: Aggregate circumcision data
      from a children's hospital was obtained from medical records. Birth place was
      also identified for circumcisions (ICD9 code 64.0) in children 12 months to 18
      years of age. Birth place is a surrogate marker of immigration status. RESULTS:
      During the 1996-2005 study period, there were 29,408 male births with an average
      newborn circumcision rate of 89%. The rate of circumcisions has declined from 93%
      in 1997 to 88% in 2005. There were 552 circumcisions performed on children 12
      months to 18 years of age during this study period. Of these, 45 were performed
      in 1996 and 81 cases were performed in 2005. Birthplace data was missing from 25%
      of these cases. For those with birthplace data available, 60% of the
      circumcisions were amongst those born in Hawai'i, 15% were born in the other 49
      states and US territories, and 24% were born in a foreign country. CONCLUSION: In
      a community in which newborn circumcision rates are high, the frequency of
      circumcision is declining, while the number of circumcisions performed in
      children aged 1-18 is increasing. The number of circumcisions performed in non-US
      born children is disproportionately higher than what would be expected suggesting
      that the post-infant circumcision rates for this age group is higher in
      immigrants.

PMID- 19385374
TI  - Racial disparities in Pacific Islanders undergoing renal transplant evaluation.
AB  - Pacific Islanders currently comprise 35% of all end-stage renal disease patients
      in Hawai'i but a much smaller proportion of those who undergo renal transplant.
      The purpose of this study to determine the reasons for such a disparity. In this
      retrospective review of 207 patients who were referred for renal transplant
      evaluation, 18.8% were Pacific Islanders. Patients attended a kidney transplant
      class, were offered evaluation and were placed on the waiting list if deemed
      appropriate. Of patients that were eventually placed on the list, 18.6% were
      Pacific Islander. There was no difference in age, gender body mass index,
      presence of diabetes, number with potential living donors, dialysis status, time
      from the referral to attending class and the time from the class to listing
      between Pacific Islanders and other ethnic groups. Pacific Islanders who are
      referred to our transplant program are able to make it through the evaluation and
      be listed with the same success as other patients. The problem in racial
      disparities in Hawai'i involves referral to the transplant center. Whether the
      problem of referral is due to other medical comorbidities or noncompliance is not
      clear and will require further investigation.

PMID- 19385376
TI  - Medical student research at John A. Burns School of Medicine (JABSOM), University
      of Hawai'i.

PMID- 19385378
TI  - Biased articles.

PMID- 19385377
TI  - Ovarian cancer: risks.

PMID- 19385379
TI  - A brief inspection of the navel.

PMID- 19385380
TI  - Inflammatory bowel disease.

PMID- 19385381
TI  - Epidemiology of inflammatory bowel disease and overview of pathogenesis.

PMID- 19385382
TI  - Medical therapy of IBD in 2009.

PMID- 19385383
TI  - OSCCAR: Ocean State Crohn's and Colitis Area Registry.

PMID- 19385384
TI  - What's new in surgical treatment for Crohn's disease.

PMID- 19385386
TI  - Advances in imaging in Crohn's disease.

PMID- 19385385
TI  - Ileal pouch-anal anastomosis for ulcerative colitis--the Rhode Island experience.

PMID- 19385387
TI  - Family caregiver health: what to do when a spouse or child needs help.

PMID- 19385388
TI  - Traumatic brain injury in Rhode Island.

PMID- 19385389
TI  - Pain and prejudice: the use of chronic narcotic therapy in medical practice.

PMID- 19385390
TI  - A time for real "change" in primary care.

PMID- 19385391
TI  - A frantic assemblage of words.

PMID- 19385392
TI  - Standards must be priority.

PMID- 19385393
TI  - Slump in cost of living sees nurses receive above-inflation pay rise.

PMID- 19385394
TI  - A suitable case for treatment.
AB  - Although mental health care in prion has improved, there is still a long way to
      go.

PMID- 19385395
TI  - The bone detectives.
AB  - With an ageing population, the number of people with osteoporosis is set to
      increase. Nurses are identifying the condition and those at risk of it.

PMID- 19385396
TI  - Unlocking a safer system.
AB  - Having to hunt for the nurse who had the drug cupboard keys was taking time away
      from patient care. A simple solution has changed that.

PMID- 19385397
TI  - Happy families.

PMID- 19385398
TI  - A matter of context.

PMID- 19385399
TI  - Diagnosis and management of cystic fibrosis-related diabetes in adults.
AB  - Diabetes is an increasingly common complication in adolescents and adults with
      cystic fibrosis. However, there is little research on the physical and
      psychological effects of having both cystic fibrosis and diabetes. Some
      individuals find it difficult to cope with the increased burden of a second
      chronic disease. Nurses and other healthcare professionals should endeavour to
      identify appropriate ways to support these individuals. This article provides an
      overview of cystic fibrosis-related diabetes, including diagnosis, treatment,
      nutrition and other important factors.

PMID- 19385400
TI  - Urinary catheterisation: assessing the best options for patients.
AB  - There are two methods of draining urine from the bladder via a catheter. They
      involve intermittent catheterisation or the use of an indwelling catheter. This
      article outlines the history of urinary catheterisation, reasons for its use, and
      the rationale for choosing the most appropriate option for patients with urinary
      dysfunction. Many articles have been written on urinary catheterisation, reasons
      for insertion and probable catheter-associated problems. In deciding which method
      of catheterisation is required, whenever possible the needs and views of the
      patient should be discussed before a decision is taken.

PMID- 19385401
TI  - Reducing the risks associated with urinary catheters.
AB  - The NHS strives to create and promote a safe environment for patient care in
      which risks are minimised. Urinary catheterisation is a common healthcare
      procedure but it is an invasive intervention that carries the risk of infection.
      Evidence-based guidelines have been developed to minimise the risks associated
      with these devices and to allow healthcare professionals to implement best
      practice at all times. This article looks at evidence-based guidance and
      technological innovations aimed at reducing infection risks and improving patient
      outcomes.

PMID- 19385402
TI  - Norovirus.

PMID- 19385403
TI  - Administering medication to adult patients with dysphagia.
AB  - Medication administration errors are almost twice as frequent in mental health
      inpatients with swallowing difficulties than those without. Similar research has
      not been done in non mental-health patients. But dysphagia is a common symptom
      and this supplement aims to outline and describe the reasoning behind the
      national guidelines on medication administration in dysphagia, to promote safe
      administration of medicines and reduce the level of errors associated with
      medication administration in dysphagia.

PMID- 19385404
TI  - We are all in it together.

PMID- 19385405
TI  - Putting thought into practice.

PMID- 19385406
TI  - Build an effective team.

PMID- 19385407
TI  - Nurses struggle to care for cancer survivors.

PMID- 19385408
TI  - Why nurses are vital in beating cancer.

PMID- 19385409
TI  - Does access to contraception raise teenage pregnancy rates?

PMID- 19385410
TI  - Setting up a nurse-led contraceptive clinic for young parents.
AB  - This article describes the development of a nurse-led contraceptive and sexual
      health drop-in clinic, which runs alongside an existing young parents' drop-in
      service provided by a charity called Key to the Door. The clinic provides young
      parents, whose average age is 16-25, with access to a variety of first-issue
      contraceptive methods and screening for sexually transmitted infections (STIs).
      The article explains how the service was developed and provides information from
      an audit, which shows the clinic's effectiveness and positive outcomes for
      service users.

PMID- 19385411
TI  - Why is specialist nursing care pivotal in managing under-age pregnancy?

PMID- 19385412
TI  - A nurse-led minor illness and injury home-visiting service for young children.
AB  - This article outlines an initiative to deliver a nurse-led home-visiting service
      to support families and develop their knowledge and skills in managing unwell or
      injured children. The service has reduced unnecessary A&E attendances and has
      provided extra support for families with children aged 0-5 years in one of the
      country's most deprived areas.

PMID- 19385413
TI  - Interventions for preventing weight gain after people quit smoking.

PMID- 19385414
TI  - Emergency oxygen delivery 2: patients with asthma and COPD.
AB  - This is the second of a two-part unit on the use of emergency oxygen in adults.
      Part 1 outlined the main recommendations of the recently published British
      Thoracic Society guidance. It also examined managing breathlessness in non
      hypoxaemic patients. This part discusses some potential changes to clinical
      practice and provides practical examples on administering oxygen to patients with
      acute asthma and COPD. It also outlines issues around administering oxygen that
      lack evidence and need good-quality studies.

PMID- 19385415
TI  - Building an online community to support nurse education.
AB  - This article explores the topic of developing an online community for student
      nurses to use in learning. It examines the different definitions and types of e
      learning and outlines the online community's role in healthcare education,
      together with some of its pitfalls. A comparison is then made to the process of
      bidding on eBay, to determine possible similarities.

PMID- 19385417
TI  - 'Nursing tries to patch up the wounds of poverty'.

PMID- 19385416
TI  - Nurses are in a key position to reduce the number of people getting cancer.

PMID- 19385418
TI  - On spiritual care in a secular health service.

PMID- 19385419
TI  - Introduction to the symposium--humanism in healthcare management.

PMID- 19385420
TI  - Ten approaches for enhancing empathy in health and human services cultures.
AB  - Empathy is defined as a predominantly cognitive attribute that involves an
      understanding of experiences, concerns and perspectives of another person,
      combined with a capacity to communicate this understanding. Empathy in the
      context of clinical care can lead to positive patient outcomes including greater
      patient satisfaction and compliance, lower rates of malpractice litigation, lower
      cost of medical care, and lower rate of medical errors. Also, health
      professionals' wellbeing is associated with higher empathy. Enhancing empathic
      engagement in patient care is one of the important tasks of medical education. In
      this article, I briefly describe 10 approaches for enhancing empathy in the
      health care environment: improving interpersonal skills, audio- or video-taping
      of encounters with patients, exposure to role models, role playing (aging game),
      shadowing a patient (patient navigator), hospitalization experiences, studying
      literature and the arts, improving narrative skills, theatrical performances, and
      the Balint method. I conclude that empathic engagement in the health care and
      human services is beneficial not only to the patients, but also to physicians,
      other health care providers, administrators, managers, health care institutions,
      and the public at large.

PMID- 19385421
TI  - The health care leader as humanist.
AB  - This paper discusses the nature of humanism in healthcare management and
      leadership. Humanism in healthcare management should entail serving 1) patients
      and their families, 2) organizational members, and 3) the community. The article
      describes how humanism is largely absent from healthcare organizations as a
      critical and important value. In the twentieth century, a number of models of
      healthcare leadership were developed that were humanistic in focus. These models
      primarily stressed the value of attention by leaders on the needs and values of
      people working in the organization. However, humanistic, healthcare leadership
      involves not only motivating and empowering employees, but a primary, essential
      focus is for leaders to create environments that support and uplift patients and
      their families. Humanistic care in healthcare organizations can be facilitated by
      leaders establishing positive, supportive, and empowering environments for
      clinicians and other employees. Secondly, managers can establish programs to
      develop and train employees to provide humanistic care.

PMID- 19385422
TI  - Caring science and human caring theory: transforming personal and professional
      practices of nursing and health care.
AB  - This article explores some of the latest developments of the emergence of Caring
      Science as the moral, theoretical, and philosophical foundation for nursing,
      leading to transformative personal/professional practices. Through nurse's taking
      responsibility for advancing nursing qua nursing, practitioners, patients, and
      systems alike are witnessing a revolution in nursing, which is restoring the
      heart of nursing and health care through theory-guided philosophical practices of
      heart-centered love and caring as the foundation for healing.

PMID- 19385423
TI  - Humanism in nursing homes: the impact of top management.
AB  - We provide a review of ways in which top managers of nursing homes can provide or
      impact the humanistic component of care provided in their facilities. We describe
      the nursing home top management team; the role of top managers in nursing homes;
      the role of top managers as leaders in the nursing home; the literature examining
      the impact of top managers in nursing homes; and, examine developments in the
      nursing home industry that are influencing (or could potentially influence) the
      humanistic components of care. We conclude with suggestions for top managers,
      nursing home owners, and policy makers to create more caring humanistic
      environments. Suggestions include resident-directed care initiatives and culture
      change.

PMID- 19385424
TI  - Organizational and individual perspectives on caring in hospitals.
AB  - Caring and humanism in hospitals exist on both the organizational and the
      individual levels. This paper identifies key organizations and foundations that
      have succeeded in promoting or fostering caring environments in hospitals. These
      include the Picker Institute, the Baptist Healing Trust, Sage Consulting, and the
      Caritas Consortium. Exemplary, caring clinicians in hospitals are also described.
      These clinicians developed positive relationships with patients and in interviews
      communicated a number of approaches to express caring to patients. Health and
      human services managers can take a number of steps to promote caring among their
      clinicians. However, they must implement a culture and a reward system that
      encourages humanism.

PMID- 19385425
TI  - [Myocardial infarction: peculiarities of lipid metabolism, oxidative and
      antioxidative potential].
AB  - Characteristics of lipid metabolism, lipid peroxidation products (LPP), and
      antioxidative potential were determined in patients with acute myocardial
      infarction. Minor variations of serum total cholesterol, LDL, and triglycerids
      were detected in patients with small-focal MI. After completion of therapy
      cholesterol dropped only in patients with transmural infarction. LDL cholesterol
      was low prior to therapy in all patients and continued to decrease in transmural
      MI. All patients had high dienic congugate levels in plasma and erythrocytes that
      did not change under effect of baseline therapy. The level of secondary LPP (MDA)
      in erythrocytes was high and remained unaltered during treatment. Antioxidative
      potential measured as SOD activity was elevated in all patients. Glutathione
      reductase, glutathione peroxidase, and catalase activities decreased throughout
      the treatment period. Patients with acute IM developed oxidative stress during
      heart attack, it persisted for a long time and was responsible for suppression of
      pentosophosphate cycle in erythrocytes associated with low activity of
      glutathione reductase and catalase that needed reduced NADPH2 codehydrogenase to
      manifest itself. Patients with small-focal and transmural AMI experienced
      elevation of oxidative potential in erythrocytes and membranopathy. Baseline
      therapy failed to normalize production of primary and secondary LPP in patients
      with MI and eliminate oxidative stress that developed during heart attacks and
      persisted after the termination of therapy. It is concluded that correction of
      metabolic disturbances requires antioxidative therapy to neutralize LPP.

PMID- 19385426
TI  - [An experimental luminescent immunochromatographic system].
AB  - Luminescent immunochromatographic assay for antigens of microorganisms was
      developed to detect antigens and cells of microorganisms, toxins. Luminescent
      submicrone latex particles, quantum labels, ganglioside-containing liposomes with
      sulforhodamine-01 in the internal volume were used as a luminescent mobile phase
      for conjugation with antibodies. Devices for registration of luminescent
      immunochromatograms were developed. Submicrone latexes were shown to have
      advantages over quantum labels, ganglioside-containing liposomes with
      sulforhodamine-101 and colloid gold for immunochromatographic procedures.
      Sensitivity of luminescent latex-based immunochromatographic indicator element
      was 3-30 that elements based on colloid gold conjugates for identical
      microorganisms and elements.

PMID- 19385427
TI  - [Electroencephalographic signs of internal attention in the mental counting of
      heart beats].
AB  - Attention is regarded as a dynamic spatio-temporal structure reflected inter alia
      in distribution patterns of total spectral power density of EEG alpha-rhythm
      obtained in volunteers. Factors influencing formation, time of existence and
      parameters of such structure are related to dynamics of the observation object
      (heart), to the use of individual combinations of perception codes, by the
      volunteers etc. It is supposed that localization of a single "cerebral area of
      attention" can not be universal for all individuals. An approach to the
      description of different types of attention to one's own heart is proposed in
      which attention is characterized based on distinguishing critical points or EEG
      registration zones in which the loss of system's stability is most likely
      reflected as transition to another functional state.

PMID- 19385428
TI  - [Problems of experimental simulation of hypo- and hyperthyroidism].
AB  - This paper reviews main conventional and new experimental models of hypo- and
      hyperthyroidism. The authors propose classification of methods (physical,
      chemical, and biological) for modulation of thyroid activity and criteria for
      life-time and postmortem diagnosis of hypo- and hyperthyroidism. New approaches
      to simulation of diffuse toxic goiter in animals are considered, advantages and
      limitations of different models are compared.

PMID- 19385429
TI  - [Classification of lectins as universal regulator molecules of biological
      systems].
AB  - Modern concepts of lectin classification reflecting tendencies in the development
      of functional classification of lectins (Ln) and Ln-like proteins are presented.
      Classification of bacterial Ln is proposed. Classification of Ln and Ln-like
      proteins of plants, animals, and bacteria is based on 8 major elements of protein
      secondary structure that allows for the evaluation of topographic diversity of
      their surfaces, potential compatibility of bacterial, vegetable, and mammalian Ln
      molecules and possible variants of their co-functioning.

PMID- 19385430
TI  - [Penitentiary microenvironment as a risk factor of psychosomatic health
      (digest)].
AB  - This analytical survey shows that health status of jail prisoners in Russia as
      worldwide is strikingly different from that of the general population. The
      difference is accounted for by the concentration of socially dysadapted
      individuals in penitentiary institutions, conditions and relations facilitating
      the spread of certain infections in prisons. This problem is of importance for
      society at large because most prisoners sooner or later come back to the normal
      life and influence national health statistics. Moreover, penitentiary
      institutions constitute an important reserve of national health care systems
      since prevention and treatment of a large group of diseases among the prisoners
      facilitate the work of public health facilities serving the general population.

PMID- 19385431
TI  - [Scientific and pedagogic school of academician I. P. Pavlov].

PMID- 19385432
TI  - Closing the gap in a generation: health equity through action on the social
      determinants of health. A report of the WHO Commission on Social Determinants of
      Health (CSDH) 2008.

PMID- 19385433
TI  - Predictive tool for estimating the potential effect of water fluoridation on
      dental caries.
AB  - OBJECTIVE: To provide a tool for public health planners to estimate the potential
      improvement in dental caries in children that might be expected in a region if
      its water supply were to be fluoridated. BASIC RESEARCH DESIGN: Recent BASCD
      (British Association for the Study of Community Dentistry) dental epidemiological
      data for caries in 5- and 11-year-old children in English primary care trusts in
      fluoridated and non-fluoridated areas were analysed to estimate absolute and
      relative improvement in dmft/DMFT and caries-free measures observed in England.
      Where data were sufficient for testing significance this analysis included the
      effect of different levels of deprivation. RESULTS: A table of observed
      improvements was produced, together with an example of how that table can be used
      as a tool for estimating the expected improvement in caries in any specific
      region of England. Observed absolute improvements and 95% confidence intervals
      were: for 5-year-olds reduction in mean dmft 0.56 (0.38, 0.74) for IMD 12, 0.73
      (0.60, 0.85) for IMD 20, and 0.94 (0.76, 1.12) for IMD 30, with 12% (9%, 14%)
      more children free of caries; for 11-year-olds reduction in mean DMFT 0.12 (0.04,
      0.20) for IMD 12, 0.19 (0.13, 0.26) for IMD 20, 0.29 (0.18, 0.40) and for IMD 30,
      with 8% (5%, 11%) more children free from caries. CONCLUSIONS: The BASCD data
      taken together with a deprivation measure are capable of yielding an age
      specific, 'intention to treat' model of water fluoridation that can be used to
      estimate the potential effect on caries levels of a notional new fluoridation
      scheme in an English region.

PMID- 19385434
TI  - Dental caries prevalence and distribution among preschoolers in Singapore.
AB  - OBJECTIVE: To describe the prevalence, severity and distribution of dental caries
      among preschoolers in Singapore. BASIC RESEARCH DESIGN: population-based, cross
      sectional study. SETTING: 13 randomly selected People's Action Party Community
      Foundation (PCF) Education Centers, the main provider of preschool education in
      Singapore. PARTICIPANTS: 1782 children aged 3-6 years. MAIN OUTCOME MEASURES: The
      caries status was evaluated by using WHO examination procedures and diagnostic
      criteria. RESULTS: About 40% children (26%, 37%, and 49% for 3-4, 4-5, and 5-6
      year-olds, respectively) were affected by caries. The mean (SD) deft and defs
      were 1.54 (2.75) and 3.30 (7.49), respectively. About 90% of the affected teeth
      were decayed teeth. A significantly skewed distribution of caries lesions was
      revealed, indicating that 16% children with high caries activity (deft > or =4)
      were carrying 78% lesions. Rampant caries, defined as caries affecting the smooth
      surfaces of two or more maxillary incisors, was found in 16.5% of children. About
      61% of affected surfaces were smooth surfaces. Malays and boys tended to have
      more rampant caries. Higher caries severity and treatment need were found among
      Malays and children in the low socio-economic group. CONCLUSIONS: Caries is a
      severe oral health problem for Singaporean preschoolers, especially in the Malay
      community and among children with low economic status.

PMID- 19385435
TI  - Oral health in German children, adolescents, adults and senior citizens in 2005.
AB  - OBJECTIVE: The aim of this field study (the "Fourth German Oral Health Study")
      was to obtain representative data on caries (DMFT index), periodontitis (CPI) and
      prosthetic status in the German population and to evaluate changes in the oral
      health of the German people as compared with the findings of the Third German
      Oral Health Study conducted eight years previously. BASIC RESEARCH DESIGN: The
      study took the form of a population-representative cross-sectional survey with
      random samples, and was complemented by a questionnaire to reveal sociological as
      well as behavioural data. PARTICIPANTS: The age cohorts in the present study were
      12-year-olds (children), 15-year-olds (adolescents), 35- to 44-year-olds (adults)
      and 65- to 74-year-olds (senior citizens). RESULTS: All age groups showed
      considerable improvements in oral health with respect to caries. Of the children,
      70.1% were free of dentine caries and the mean DMFT value was 0.7. In adults and
      senior citizens both the DMFT value and the number of missing teeth and
      edentulousness declined. With regard to periodontal conditions, increasing
      prevalence of moderate and severe findings was recorded in adults and senior
      citizens, owing probably to the larger number of natural teeth remaining in the
      oral cavity. CONCLUSION: The study documents a distinct improvement in oral
      health in the German population. Interrelated with the higher numbers of
      remaining natural teeth a higher prevalence of moderate and severe periodontal
      conditions in German adults and senior citizens was observed.

PMID- 19385436
TI  - Caries prevalence and fluoride use in low SES children in Clermont-Ferrand
      (France).
AB  - OBJECTIVE: To evaluate the association between dental caries experience and
      preventive behaviours of children residing in a deprived area in Clermont-Ferrand
      (France). PARTICIPANTS AND METHODS: All 4-5 yr-olds attending nine schools in
      deprived areas of the city were invited to participate and 81% (n=282) consented
      and were examined. Dental caries was recorded at the dentine threshold. Parents
      completed a questionnaire concerning family demographics and the child's use of
      fluoride. Non-parametric tests and logistic regression assessed the relative
      importance of SES and fluoride variables on dental status (dt>1). RESULTS: Fifty
      four (19%) of the examined children were living in families with an immigrant
      background, 33% were fully covered by the national health insurance programme for
      deprived families. Caries experience was high; mean dft was 1.94 (3.31) and 30%
      of the children had >1 carious teeth. Thirty percent of the families reported
      using fluoridated salt. Tooth brushing once daily was reported for 39% and twice
      daily for 26%. Parents declared supervising tooth brushing for 60%. Two thirds of
      the children, according to their parents, used fluoride supplement between birth
      and two years. Supervised tooth brushing was significantly correlated with lower
      mean dt scores. Systemic fluoride use was poorly related to dental caries
      Immigrant background, family size, type of health insurance and mother's
      unemployment were significantly correlated with caries prevalence. In
      multivariate analysis, immigrant status, supervised tooth brushing and parental
      knowledge about fluoride in toothpastes were significant caries predictors.
      CONCLUSIONS: The majority of low SES children did not practice effective caries
      prevention; few reported twice daily brushing with fluoride toothpaste. Caries
      experience was very high and much was untreated. Immigrant status, supervised
      tooth brushing and parental knowledge about fluoride in toothpastes were
      significant caries predictors.

PMID- 19385437
TI  - Previous radiographic experience of children referred for dental extractions
      under general anaesthesia in the U.K.
AB  - OBJECTIVE: To determine what proportion of children undergo radiographic
      assessment prior to referral to a dental hospital for extractions under general
      anaesthesia. BASIC RESEARCH DESIGN: This prospective survey was conducted over a
      6-month period. A data sheet was used to record the following information:
      patient's age; referrer's name and place of work (general dental practice or
      community dental service); teeth to be extracted (primary dentition and/or
      permanent dentition) and reported previous radiographic examination. Patients
      were excluded from the study if, following a clinical examination, radiographs
      were not actually deemed necessary for diagnosis and treatment planning purposes.
      Clinical setting A paediatric dentistry clinic within a dental hospital in the
      North of England. Participants 161 patients with a mean age of six years (SD =
      2.2, range = 3-14 years) who were referred to the dental hospital for extractions
      under general anaesthesia. RESULTS: Overall, 12.4% of children had reportedly
      undergone a previous radiographic assessment prior to hospital referral. A
      significantly greater proportion of children referred for permanent tooth
      extractions had been subject to radiographic examination compared to children
      referred for primary tooth extractions (46.2% as compared to 6.3%; P = 0.001 chi
      squared test). Furthermore, patients referred from the community dental service
      were significantly more likely to have had previous dental radiographs than
      children referred from general dental practice (36.9% compared to 9.3%; P = 0.003
      chi-squared test). CONCLUSIONS: Radiographs do not appear to be routinely
      employed for caries diagnosis and treatment planning in young children within
      general dental practice in the U.K.

PMID- 19385438
TI  - The prevalence of dental caries and fissure sealants in 12 year old children by
      disadvantaged status in Dublin (Ireland).
AB  - OBJECTIVE: The aim was to record dental caries levels and the presence of fissure
      sealants in 12-year-old schoolchildren whose domestic water supply had been
      fluoridated since birth in Dublin (Ireland). RESEARCH DESIGN: Cross-sectional
      study. Participants A representative, random sample of 12-year-old schoolchildren
      in north-west Dublin. OUTCOME MEASURES: Dental caries levels were recorded using
      WHO criteria and fissure sealant was recorded when sealant was detectable on a
      permanent molar tooth. Medical card ownership, as a surrogate for disadvantage,
      was recorded by use of a questionnaire. RESULTS: Three-hundred and thirty-two
      (332) children were examined. The mean DMFT was 0.80 (SD 1.24). Analysis (Mann
      Whitney U test) based on stratification of the sample according to medical-card
      status revealed no statistically significant difference between DMFT median
      scores of children of medical-card holders (i.e., social disadvantage background)
      and non medical-card holders (p-value = 0.23). However, the data revealed a
      social gradient in the presence of at least one fissure sealant. Approximately
      10% more children in the group of medical-card holders had no fissure sealants
      present. Fisher's exact test was used to examine the association between the
      absence of fissure sealants and at least one fissure sealant between the two
      groups and was considered to be statistically significant (p-value = 0.04).
      CONCLUSION: This study demonstrated a social gradient in the presence of fissure
      sealants, but no such gradient in dental caries levels. This demonstrates the
      importance of population-based measures in the prevention of dental caries, such
      as water fluoridation, in reducing oral health inequalities.

PMID- 19385439
TI  - Childhood growth and dental caries.
AB  - OBJECTIVES: The aim of the study was to examine whether the removal of carious
      teeth affected children's growth relative to that of a standard population.
      DESIGN: Longitudinal prospective observational study. SETTING: Manchester Dental
      Hospital (MDH), U.K. PARTICIPANTS: Five- and six-year-old children who attended
      for extraction of carious teeth under general anaesthesia. MAIN OUTCOME MEASURE:
      Change in height, weight and BMI standard deviation scores during the six months
      after extraction of carious teeth. METHODS AND MATERIALS: The children's dental
      caries levels, weight and height were measured prior to extraction using standard
      criteria and a single trained examiner and they were then re-measured six months
      later. The body mass index of the children was calculated and all measurements
      were converted to standard deviation scores (SDS) using the U.K. 1990 growth
      reference. Changes in growth SDS during the six months subsequent to the
      extractions were then calculated. RESULTS: Two hundred and eighteen children,
      mean (range) age 5.9 (5-6) were examined initially, of whom 131 were successfully
      followed up a mean 7.1 (0.13) months later. The participants had a mean dmft of
      7.18 (SD 3.27) at baseline and were not shorter than expected (8.3% <10th
      percentile), or more underweight (6.9% <10th percentile for weight). At follow up
      children showed a statistically significant gain in BMI SDS (mean (SD) 0.26 (37)
      p < 0.001) and a small gain in height SDS (0.05 (0.38) p = 0.05). CONCLUSION:
      This study suggests that the extraction of carious teeth in five and six year old
      children promotes weight gain and possibly growth.

PMID- 19385440
TI  - Measurement of attitudes of U.K. dental practitioners to core job constructs.
AB  - OBJECTIVES: To develop a measure to identify dental practitioner attitudes
      towards core job dimensions relating to job satisfaction and motivation and to
      test this against practice characteristics and provider attributes of U.K.
      practitioners. RESEARCH DESIGN: an 83-item questionnaire was developed from open
      ended interviews with practitioners and use of items in previously used dentist
      job satisfaction questionnaires. This was subsequently sent to 684 practitioners.
      Item analysis reduced the item pool to 40 items and factor analysis (PCA) was
      undertaken. RESULTS: 440 (64%) dentists responded. Factor analysis resulted in
      six factors being identified as distinguishable job dimensions, overall
      Cronbach's alpha = 0.88. The factors were: 'restriction in being able to provide
      quality care (F1)', 'respect from being a dentist (F2)', 'control of work (F3)',
      'running a practice (F4)', 'clinical skills (F5)', and 'caring for patients
      (F6)'. All six factors were correlated with a global job satisfaction score,
      although F1 was most strongly related (r = 0.60). Regression model analysis
      revealed that 'whether the dentist worked within the National Health Service or
      wholly or partly in the private sector' (p < 0.001), 'time since qualification'
      (p = 0.009), and the position of the dentist within the practice (whether a
      practice owner or associate dentist), (p = 0.047) were predictive of this factor.
      CONCLUSIONS: Six core job constructs of U.K. practitioners have been identified,
      together with several practice characteristics and practitioner attributes which
      predict these factors. The study demonstrates the importance of refining measures
      of dentists' job satisfaction to take account of the culture and the system in
      which the practitioner works.

PMID- 19385441
TI  - Dental general anaesthesia--will the service disappear? A pilot study.
AB  - OBJECTIVES: To identify likely future trends in recruitment of consultant
      anaesthetists to the ambulatory dental general anaesthetic (DGA) services.
      PARTICIPANTS: The sample consisted of all anaesthetic specialist registrars
      (SpRs) in their final year of training, within Mersey and South-Western Deaneries
      in the U.K. RESEARCH DESIGN: A questionnaire divided into a quantitative section
      to establish level of training in ambulatory DGA, and a qualitative section
      designed to elicit opinions and attitudes towards ambulatory DGA services.
      RESULTS: The response rate was 75% (27/36). Within both regions 81% (22/27) had
      received practical training in ambulatory DGA procedures. SpRs in the South
      Western Deanery held the greatest misgivings about the ambulatory DGA technique.
      Once appointed to Consultant position only 11% (3/27) of respondents expressed a
      definite interest in providing ambulatory DGA services. CONCLUSIONS: Within the
      Northwest and Southwest of England, most specialist registrars in anaesthetics
      receive training in ambulatory DGA, although their future commitment to the
      delivery of these services is questionable.

PMID- 19385442
TI  - Orthodontic treatment need and oral health-related quality among children.
AB  - OBJECTIVES: To determine the association between the impact of oral health on
      quality of life (OHQoL) among children and their need for orthodontic treatment.
      METHODS: Children (217) were screened for orthodontic treatment need using a
      number of professionally derived indices: Index of Orthodontic Treatment Need
      (IOTN)--Aesthetic Component (AC) and Dental Health Component (DHC); Index of
      Complexity, Outcome and Need (ICON) and the Dental Aesthetic Index (DAI). In
      addition, all children self-completed the 37-item Child Perception Questionnaire
      (CPQ), a measure of OHQoL, to assess Oral Symptoms (OS) experienced, Functional
      Limitation (FL), Emotional Well Being (EWB) and Social Well Being (SWB). RESULTS:
      Different prevalence of orthodontic treatment need was observed depending on
      occlusal indices used (ranged from 31.6% to 85.9%). However, there were
      significant correlations between the different occlusal indices (p < 0.01).
      Significant differences in overall CPQ scores existed between those with and
      without an orthodontic treatment need irrespective of occlusal indices used to
      categorize treatment need (p < 0.05); Effect sizes ranged from 0.24 to 0.51.
      However no single index's categorization of treatment need could identify
      variations in all of CPQ domain scores (OS, FL, EWB and SWB). CONCLUSION:
      Different occlusal indices (AC, DHC, ICON and DAI) prescribe a different
      prevalence of orthodontic treatment need. Those categorized as having an
      orthodontic treatment need by AC, DHC, ICON and DAI criteria had poorer overall
      OHQoL compared to those ascribed as not having a treatment need. None of the
      occlusal indices could comprehensively differentiate poorer OHQoL across all its
      domains.

PMID- 19385443
TI  - Changing dental caries levels in the 1980's, 1990's and 2005 among children of a
      Jerusalem region.
AB  - OBJECTIVE: To study caries levels and related variables among first grade and
      fourth grade schoolchildren in one Jerusalem geographic region in 2005, and
      possible changes in caries levels over three decades: the 1980s, 1990s and
      finally in 2005. METHODS: Dental caries was examined, within schools, employing
      the DMFS and defs indices, for permanent and deciduous teeth respectively.
      RESULTS: Data indicate a consistent decline in disease: a reduction from 1.64 to
      0.32 to 0.16 for DMFS, and 13.95 to 8.09 to 5.07 for defs (1983, 1992, 2005,
      respectively), among first grade children; and from 3.50 to 2.50 to 1.07 for
      DMFS, and 13.88 to 7.26 to 4.16 for defs, (1983, 1992, 2005, respectively), among
      fourth grade children. CONCLUSIONS: A consistent decrease in caries has been
      detected over three decades. Specific causal factors were not ascertained.

PMID- 19385444
TI  - CMS "never events" and other new trends in quality health care standards for
      hospitals.

PMID- 19385445
TI  - Black seed, Nigella sativa, deserves more attention.

PMID- 19385446
TI  - Level of high-sensitivity C-reactive protein in Saudi patients with chronic
      stable coronary artery disease.
AB  - BACKGROUND: Inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) is
      an independent predictor of future cardiovascular events and it predicts risk of
      incident hypertension and diabetes. The aim of this study was to determine the
      serum levels of the circulating acute-phase reactant high-sensitivity C-reactive
      protein (hsCRP) in Saudi patients with chronic stable Coronary Artery Disease
      (CAD). METHODS: This cross sectional study was conducted in the Department of
      Physiology and Department of Cardiology, College of Medicine and King Khalid
      University Hospital, King Saud University, Riyadh between August 2006 and
      December 2007. One hundred and seven individuals with chronic stable CAD and 33
      healthy, age and BMI-matched individuals were studied. Overnight fasting blood
      samples were collected, and analyzed for total cholesterol (TC), Triglycerides
      (TG), Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL) and hsCRP
      in patients with chronic stable CAD. RESULTS: TC (Control 4.41 +/- 0.57 vs CAD
      4.28 +/- 1.40, p = 0.8394) and LDL levels (Control 2.70 +/- 0.52 vs CAD 2.71 +/-
      1.20, p = 0.7963) did not differ significantly between the two groups. While
      there were significant differences in TG (Control 1.13 +/- 0.47 vs CAD 1.84 +/-
      1.10, p = 0.0135) and HDL levels (Control 1.06 +/- 0.30 vs CAD 0.71 +/- 0.25, p =
      0.0000). hsCRP levels were significantly higher in patients with CAD (5.0 +/-
      4.4) compared to healthy individuals (2.7 +/- 2.7, p = 0.0166). Frequency of low
      risk levels was significantly higher in Controls than CAD patients (24.2% vs
      8.4%, p = 0.0332) and vice versa for high risk levels (24.2% vs 51.4%, p =
      0.0110). At average risk levels frequency did not differ significantly (51.5% vs
      40.1%, p = 0.3429) between control and CAD groups. CONCLUSION: Saudi patients
      with stable chronic CAD have higher hsCRP levels compared to healthy individuals.
      Moreover the prevalence of undesirable risk levels of hsCRP is also higher in CAD
      patients.

PMID- 19385447
TI  - Prevalence of cardiomyopathy in Duchenne and Becker's muscular dystrophy.
AB  - BACKGROUND: Cardiac assessment was not done routinely in Duchenne (DMD) and
      Becker muscular dystrophy (BMD) patients in Northern region of England while
      evidence was gathering on progressive cardiomyopathy in these patients. We wanted
      to find out the prevalence, progression and clinical features of cardiac
      involvement in Duchenne and Becker muscular dystrophy. METHODS: It is a
      retrospective review of clinical, electrocardiographic and echocardiographic
      assessments. RESULTS: The notes of 52 Duchenne and Becker muscular dystrophy
      patients were reviewed out of which 32 had DMD, 6 had Intermediate muscular
      dystrophy (IMD) and 14 had BMD. Prevalence of preclinical and clinically evident
      cardiac involvement was 88.4% in DMD and BMD patients. Sixty nine% of patients
      had clinically evident cardiac involvement but only four patients had cardiac
      symptoms in the form of palpitations, out of which two were due to respiratory
      dysfunction and others was due to cardiac failure. Clinical examination of the
      rest of all of the patients was unremarkable. Electrocardiogram was abnormal in
      88.4% of patients. Conduction defects were found in 19.4% of patients.
      Echocardiogram was abnormal in 80.7% of patients but all were poor echo subjects
      including those who had normal echocardiogram. CONCLUSIONS: Though most patients
      were asymptomatic, a high percentage had evidence of preclinical and clinically
      evident cardiac involvement. So in all patients with Xp21 linked muscular
      dystrophy a routine baseline cardiac assessment should be done at the age of 10
      years and reviewed after intervals of one to two years.

PMID- 19385448
TI  - Clinical outcome in measles patients hospitalized with complications.
AB  - BACKGROUND: Measles is a highly communicable viral illness and is common cause of
      childhood mortality and morbidity. Keeping in view the high prevalence of measles
      in the developing world, we carried out this study to look into the complicated
      measles cases and clinical outcome in patients admitted in children ward of Ayub
      Teaching Hospital. METHODS: Detailed history and physical examination of all the
      hospitalized patients with complication of measles were recorded in a proforma.
      Immunization and nutritional status of each admitted patient was assessed and the
      clinical outcome of measles was compared with demographic profile. RESULT: One
      hundred thirty six hospitalized patients with complications of measles were
      studied. There was 60.3% male and 57.3% of patients were vaccinated against
      measles. Malnourished patients were 71.35% and had longer hospital stay (> 5
      days). Pneumonia (39.7%) and diarrhoea (38.2%) were the commonest complications.
      Seven children died and encephalitis (57.1%) was the commonest cause of death.
      CONCLUSION: The most common complications of measles are pneumonia and diarrhoea
      with dehydration requiring admission. Malnutrition results in more complications
      and longer hospital stay. Mortality is significantly associated with
      encephalitis.

PMID- 19385449
TI  - Onset of chilblains in relation with weather conditions.
AB  - BACKGROUND: Chilblains or perniosis is a moderately severe form of cold injury,
      localized to peripheral parts of the body, which occurs after exposure to non
      freezing temperatures and damp conditions. Although inter-individual variations
      exist with respect to susceptibility to develop chilblains, no study has been
      carried out in this region to determine the role of different weather conditions
      either alone or in combination, in predisposing the susceptible individuals to
      chilblains. The objective of this study was to determine the relationship between
      weather conditions and onset of chilblains at a moderately cold weather station.
      METHODS: This study was conducted at the Department of Dermatology, Combined
      Military Hospital, Abbottabad, from Dec 2004 to Mar 2005. All patients fulfilling
      the clinical criteria for diagnosis of chilblains were included in the study.
      These patients were interviewed and examined thoroughly. A specially designed
      proforma was filled for each patient separately. Meteorological department was
      contacted for record of weather conditions. Onset of chilblains in each patient
      was related with weather conditions of that particular month. Computer programme
      SPSS 10 was used for statistical analysis. RESULTS: Out of 111 patients, 67
      (60.4%) were males and 44 (39.6%) were females. Eighty nine (80.2%), 90 (81.1%)
      and 90 (81.1%) patients had onset in relation with lower temperature (< 10
      degrees C), relatively low atmospheric pressure (< 1500 kpa) and higher relative
      humidity (> 60%) respectively. There was statistically significant relationship
      of weather conditions with onset of chilblains when different groups, i.e.,
      elderly and young, males and females, locals and non locals, outdoor workers and
      those remaining inside most of the time and those having disease of longer or
      shorter duration were compared. CONCLUSION: The cold weather conditions that can
      be endured by humans depend on combination of the duration and the extent of the
      exposure, in addition to physiological adaptive changes. However, susceptibility
      to chilblains increases when ambient temperature is less than 10 degrees C and
      relative humidity is more than 60%. Elderly, females, outdoor workers and those
      having chronic or recurrent episodes of chilblains are less tolerant to cold
      weather and develop the disease under lesser ambient cold.

PMID- 19385450
TI  - Efficacy of cervicothoracic sympathectomy versus conservative management in
      patients suffering from incapacitating Raynaud's syndrome after frost bite.
AB  - BACKGROUND: Raynaud's syndrome is a known complication of cold injuries. Stress,
      smoking and metabolic diseases may further aggravate the disease course. The
      purpose of this study was to determine the efficacy of Cervico-thoracic
      sympathectomy as compared to conservative management in severe Raynaud's syndrome
      after frostbite. METHODS: This non-randomized controlled trial was conducted at
      Railway Hospital, Rawalpindi and Islamic International Medical Complex, Islamabad
      between January 1999 and June 2006. All patients sustained severe cold trauma in
      the mountain ridges of Himalayas in Kashmir. In all cases, an informed consent
      was obtained from patients and families. All operations performed were free of
      charges. Out of the total 48 patients who developed incapacitating Raynaud's
      syndrome of the upper limbs after frost bite, 17 patients underwent thoracic
      sympathectomy through anterior supraclavicular route. Remaining 31 patients were
      treated conservatively and were placed in the control group. Data was collected
      on pre-designed proforma and assessed using SPSS (version 11). Chi-square test
      was applied to assess the effectiveness of the two treatment modalities. RESULTS:
      All operated cases initially showed improvement in symptoms and incapacitation.
      Among sympathectomised patients, 11 patients became symptom free and 3 patients
      showed mild but improved symptoms. Two patients after initial transient
      improvement developed incapacitating symptoms requiring further treatment, one
      patient developed gangrene ofdistal phalanx nine month after sympathectomy
      requiring amputation of the finger. Frequency of attacks and duration between the
      attacks reduced in all operated patients of cervical sympathectomy (p < 0.05) as
      compared to conservative management. CONCLUSION: Cervical sympathectomy is a very
      effective modality of treatment in patients having severe Raynaud's disease of
      upper limbs secondary to frost bite.

PMID- 19385451
TI  - Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella
      sativa, in mice and rats.
AB  - BACKGROUND: Thymoquinone is the major active principle of Nigella sativa (N.
      sativa) and constitutes about 30% of its volatile oil or ether extract. N. sativa
      oil and seed are commonly used as a natural remedy for many ailments. Using
      modern scientific techniques, a number of pharmacological actions of N. sativa
      have been investigated including immunostimulant, anti-inflammatory, anticancer,
      antioxidant, antihistaminic, antiasthmatic, hypoglycemic, antimicrobial and
      antiparasitic. There are only few reports regarding the toxicity of thymoquinone.
      METHODS: The present study was carried out to determine LD50 of thymoquinone both
      in mice and rats, orally as well as intraperitoneall, by the method of Miller and
      Tainter. Autopsy and histopathology of liver, kidney, heart and lungs were also
      determined. RESULTS: The LD50 in mice after intraperitoneal injection was
      determined to be 104.7 mg/kg (89.7-119.7, 95% confidence interval) and after oral
      ingestion was 870.9 mg/kg (647.1-1094.8, 95% confidence interval). Whereas, LD50
      in rats after intraperitoneal injection was determined to be 57.5 mg/kg (45.6
      69.4, 95% confidence intervals) and after oral ingestion was 794.3 mg/kg (469.8
      1118.8, 95% confidence intervals). The LD50 values presented here after
      intraperitoneal injection and oral gavages are 10-15 times and 100-150 times
      greater than doses of thymoquinone reported for its anti-inflammatory, anti
      oxidant and anti-cancer effects. CONCLUSION: Thymoquinone is a relatively safe
      compound, particularly when given orally to experimental animals.

PMID- 19385452
TI  - Evaluation of restoration of sensitivities of resistant Staphylococcus aureus
      isolates by using cefuroxime and clavulanic acid in combination.
AB  - BACKGROUND: The present study was planned to observe the activity of cefuroxime,
      a second generation cephalosporin after combining it with a beta-lactamase
      inhibitor calvulanic acid. The study was conducted to evaluate the restoration or
      increase in sensitivity of beta-lactamase producing isolates of Staphylococcus
      aureus. METHODS: Staphylococcus aureus were identified by standard procedures.
      For beta-lactamase detection chromogenic Nitrocefin impregnated sticks were used.
      The sensitivity of the bacteria to the antibiotic disks was measured by disk
      diffusion method using standard zone diameter criteria given by National
      Committee of Clinical Laboratory Standards. RESULTS: The disks of cefuroxime with
      clavulanic acid had developed larger zones of inhibition. The activity of
      cefuroxime against Staphylococcus areus was significantly increased by clavulanic
      acid. CONCLUSION: Clavulanic acid if used in combination with cefuroxime, can
      improve the antimicrobial activity of cefuroxime against beta-lactamase producing
      Staphylococcus aureus.

PMID- 19385453
TI  - Evaluation of cervical cerclage for sonographically incompetent cervix in at high
      risk patients.
AB  - BACKGROUND: To determine the impact of Cervical Cerclage (CC) for prolongation of
      pregnancy, maternal and foetal outcome. METHODS: This Descriptive cross-sectional
      study was conducted over a period of 2 years patients with history of two or more
      recurrent midtrimester abortions/preterm deliveries were included. Those with
      abnormal foetus, vaginal bleeding and choreoamneonitis were excluded. All
      patients were subjected to transvaginal sonography. Those having sonographic
      evidence of cervical shortening/dilatation/cone formation were subjected to
      McDonald suture. Age, parity, period of gestation and aetiological factors were
      determined. RESULTS: Results were evaluated on the basis of pregnancy
      prolongation, 14-28 weeks (7.5%), 28-36 weeks (18.7%), 35-37 weeks
      (73.7%),vaginal delivery in (70%), instrumental (1305%), Caesarean section
      (17.5%),miscarriage (7.5%), prematurity (18.7%), term delivery (73.7%), prenatal
      death (13.7%), foetal survival rate (85.1%). No intraoperative complication
      found. During pregnancy premature rupture of membrane (3.7%), abruption (2.5%),
      severe pre-eclampsia (3.7%). During labour cervical dystocia was found in (2.5%),
      foetal distress (8.7%), mal-presentations (6.2%), cervical trauma (3.7%).
      CONCLUSION: We determined a high success rate of cervical cerclage on properly
      selected patients with sonographic evidence of cervical changes. Cervical
      sonography can be a valuable adjunct to clinical evaluation of these patients.

PMID- 19385454
TI  - Awareness among barbers about health hazards associated with their profession.
AB  - BACKGROUND: Barbers are important professionals of the community which are still
      owned, cared and financed by the community especially the rural one. Barbers
      besides performing duties in social events like marriage, circumcision etc is
      also responsible for hair and nail cutting. In urban settings they have developed
      their profession by incorporating facial massage and make-up. It is the need of
      their profession to utilize instruments like knife, blades etc. The objective of
      the study was to assess awareness among barbers regarding health hazards related
      to their profession and to identify professional practices linked with infection
      transmission. METHODS: This descriptive cross sectional study was conducted in
      Kharian city of district Gujrat, located almost mid-way between Lahore and
      Islamabad, from June 2003 to September 2003. Sample of 50 barbers were selected
      by simple random sampling technique. Data was collected by using a semi
      structured questionnaire and a checklist. Data was analyzed using SPSS 10.
      RESULTS: The mean age of barbers interviewed was 33.3 years with SD +/- 8.3. It
      was found that 29 (58%) barbers denied about any health hazards associated with
      their profession whereas 21 (42%) had knew about hepatitis, AIDS; they also
      described the role of contaminated blades, clips, towels, apron, and combs in
      causing skin problems. It was observed that 90% of barbers did not wash hands,
      80% did not change the apron, 66% did not change towel during barbering services
      to different customers. Besides 7 (14%) barbers were also performing minor
      surgeries like circumcision, in growing toe nail excision and abscess drainage.
      There was significant difference in level of awareness among barbers in respect
      of age; educational status and duration of working. Age group (15-25) had better
      knowledge about the health hazards than barbers in age group (26-50). There is a
      significant difference (p < 0.05) in the awareness of those who got formal
      education. As for the effect of media on the knowledge of these workers, it was
      observed that 78% of them had the access to TV and out of these 69% had
      significant knowledge about health hazards related to barbering profession.
      CONCLUSION: The level of knowledge among barbers about health hazards associated
      with their profession is very poor. Majority of them do not have any perception
      of unhealthy working practices in barbering. Awareness about threat of receiving
      hazardous infection from their customers is also unsatisfactory.

PMID- 19385455
TI  - Comparative analysis of disease activity in patients of chronic hepatitis B
      virus, with and without superinfection with hepatitis D virus; an experience at
      tertiary care centre.
AB  - BACKGROUND: The hepatitis D virus super-infection contributes significantly to
      the morbidity and mortality of hepatitis B virus infection. The objectives were
      to describe the incidence of Hepatitis D virus and comparative analysis of
      disease activity in patients of chronic hepatitis B virus, with and without super
      infection of hepatitis D virus. METHODS: This Cross-sectional comparative study
      was conducted at Department of Medicine and Gastroenterology Clinic Jinnah
      Postgraduate Medical Centre, Karachi, Pakistan from February 2007 to July 2007.
      HBsAg positive patients who attended our Gastroenterology clinic were selected
      for the study. After screening for Anti-HDV these patients were segregated in to
      Anti-HDV positive and negative groups. Data was analyzed on SPSS 12. RESULTS:
      Eighty-four patients were selected. Seventy-three patients who fulfilled the
      inclusion criteria were enrolled in to the study. Anti-HDV was positive in 23
      (31.5%) patients. Among these 23 anti-HDV positive, HDV-RNA was detected in 15
      (75%) patients. The differences of age, gender, marital status and area of
      residence whether rural or urban were not significant between the two groups. HBV
      DNA was significantly suppressed in majority of anti-HDV positive patients (p =
      0.019). Mean serum ALT levels were significantly higher in patients who had HDV
      infection (p = 0.014). CONCLUSION: HDV infection was common in this series of
      patients with a frequency of 31.5%. All patients of chronic HBV should be
      screened for HDV whether they are asymptomatic HBV carriers or have chronic
      active hepatitis particularly when they have raised serum ALT.

PMID- 19385456
TI  - Extrapulmonary tuberculosis in Lady Reading Hospital Peshawar, NWFP, Pakistan:
      survey of biopsy results.
AB  - BACKGROUND: Tuberculosis is a disease of poor countries. In the recent years,
      there has been an increase in the occurrence of extra-pulmonary tuberculosis
      (EPTB) world over. As very little data is available regarding the situation of
      EPTB in NWFP, this study was conducted to asses its frequency in various organ
      systems of the body and to evaluate the role of demographic factors like sex and
      age in its causation. METHODS: A total of 525 cases of EPTB diagnosed
      histopathologically in the Department of Pathology, Lady Reading Hospital
      Peshawar in the years 2002-2005 were included in the study. Age, sex and sites of
      biopsies were recorded. RESULTS: High female preponderance was noted with a M:F
      ratio of 1:2. Mean age was 35 years and 70% of the patients were in the age group
      15-45 years. Lymph nodes were the most common site of EPTB, involved in 66.4% of
      the cases. CONCLUSION: EPTB has high rates in females in their reproductive age.
      Tuberculous lymphadenitis is the most common form of EPTB. High occurrence of
      EPTB in female population needs immediate attention of tuberculosis control
      programs.

PMID- 19385457
TI  - Risk to household contacts of tuberculous patients based on Mantoux test and
      antibody titre.
AB  - BACKGROUND: Tuberculosis, being an infectious disease, carries a risk of
      infection to contacts attending tuberculous patients. This study was conducted to
      evaluate the risk for household contacts of tuberculous patients as compared to
      non-contacts. The study was conducted at PGMI, Gulab Devi Hospital and Defence
      Housing Authority Lahore. The study included 120 household contacts and 80 non
      contacts. METHODS: A Cross sectional study for evaluation of antituberculous
      antibodies levels by ELISA method in two groups; Mantoux positive household
      contacts 49, Mantoux negative household contacts 71 and normal healthy persons
      'non contacts' 80. Routine Haematological investigations like HB, TLC and ESR
      were done by conventional methods and all the sera of 200 subjects included in
      the study were tested for IgM, IgG and IgA anti tuberculous antibodies by enzyme
      linked immunosorbant assay (ELISA). Purified protein derivative 0.1 ml containing
      5 TU was injected intradermally. The test was read after 72 hours by measuring
      the induration around injection site of forearm. RESULTS: There was no difference
      in the average age of the household contacts and non-contacts. The complaints of
      pyrexia, night sweats and weight loss were more in house hold contacts as
      compared to non-contacts. The awareness about BCG vaccination was equal in both.
      There were 49 contacts with positive Mantoux test while negative Mantoux test was
      found in 71 contacts. There were only three Mantoux positive among eighty non
      contacts. There was no significant difference in the presence of IgM among
      household contacts as compared to non-contacts. However both IgG and IgA were
      present in significantly higher number of household contacts compared to non
      contacts. CONCLUSION: Household contacts of patients suffering from active
      pulmonary tuberculosis have more chances of being infected with Mycobacterium
      tuberculosis as compared to the healthy non-contact, as shown by the higher
      levels of antituberculous antibodies & positivity of Mantoux test.

PMID- 19385458
TI  - Frequency of dyslipidaemia in type 2 diabetes mellitus in patients of Hazara
      division.
AB  - BACKGROUND: Diabetes mellitus increases the risk of atherosclerotic vascular
      disease because of associated dyslipidaemia. Many studies advocate aggressive
      management of lipid disorders in Type 2 Diabetes to decrease these complications.
      This study was carried out to know the frequency of dyslipidaemia in our patients
      and also to determine that whether patients with good glycaemic control (HbA1c <
      or = 8%) are having better lipid profile than poorly controlled group. Cross
      sectional survey was conducted in Medical OPD and Medical 'B' Ward of Ayub
      Teaching Hospital, Abbottabad between March 2006 to March 2007. METHODS: Patients
      with Type 2 Diabetes mellitus coming to Medical OPD as well as among those
      admitted in Medical 'B' Ward fulfilling the inclusion criteria were selected.
      Blood was taken in the fasting state for lipid profile, fasting blood glucose and
      glycosylated haemoglobin determination. RESULTS: Among 100 patients with Type 2
      Diabetes, 78 were found to have hypertriglyceridaemia, while, 92 had LDL
      Cholesterol in borderline cardiovascular risk status. Out of 78 patients with
      hypertriglyceridaemia 46 (59%) were poorly controlled diabetics (HbA1c > 8%)
      emphasizing the importance of good glycaemic control. However none of our
      patients had a low HDL-Cholesterol as found in some other studies. CONCLUSION:
      Hypertriglyceridaemia along with impaired LDL-Cholesterol is present in majority
      of our patients. Good glycaemic control does affect the lipid profile in Type 2
      Diabetes mellitus. However to provide the benefits of lipid lowering therapy to
      our patients, as confirmed in many studies, we need more awareness and placebo
      controlled double blind studies.

PMID- 19385459
TI  - An audit of the quality of care indicators for the management of diabetes in
      family practice clinics in Karachi, Pakistan.
AB  - BACKGROUND: Management of diabetes is a painstaking and careful approach. This
      study was aimed to evaluate the quality of care for the management of diabetes
      provided by family practitioners to their patients having diabetes. This is a
      retrospective audit of medical records conducted in a tertiary care teaching
      hospital of private sector in Karachi for one month. METHODS: For this study, 150
      medical records of patients with type 2 diabetes that visited family practice
      clinics for their diabetes care were examined. A total of 88 patient's medical
      records were selected and analyzed who attended the studied clinics for at least
      one year and had minimum of four out-patient visits. Majority (68%) of the
      audited medical records were of females. RESULTS: Of the total medical records
      analyzed, only one-quarter of the cases qualified the criteria of 'excellent' or
      'good' diabetes care. Monitoring of body weight of the patient was only one
      indicator which was according the recommendations in 100% case at every visit.
      The other nearest quality of care indicator documented was blood glucose advice
      at every visit in 79.5% (95% CI: 71.1-87.9) of cases. Physical activity
      advised/reinforced at every visit was least observed (27.3%; 95% CI: 18.0-36.6).
      In addition, blood sugar control was reported in less than a quarter (23.9%) with
      95% CI of 15.0-32.8. CONCLUSION: This work has identified a big gap in the
      management of type 2 diabetes provided by family practitioners. In addition,
      majority of the patients found to have poor glycemic control. Interventions are
      suggested to improve the quality of diabetes care. More such audits and research
      are recommended at the larger scale.

PMID- 19385460
TI  - Maternal morbidity and mortality due to primary PPH--experience at Ayub Teaching
      Hospital Abbottabad.
AB  - BACKGROUND: Postpartum Haemorrhage (PPH) remains a significant cause of maternal
      mortality and morbidity like hypovolemic shock, anaemia, multi organ failure,
      consumptive coagulopathy, disseminated intra vascular coagulation (DIC), blood
      transfusion related complications and hysterectomy leading to loss of
      childbearing potential. The present study was conducted to determine the
      frequency of PPH and the associated maternal morbidity at the Department of
      Gynaecology Unit 'B', Ayub Teaching Hospital Abbottabad. METHODS: The study was
      carried out in the Department of Obstetrics and Gynaecology Unit B of the Ayub
      teaching Hospital Abbottabad from 18th April 2006 to 17 July 2006. The study
      population included all cases admitted with primary PPH during the study period.
      For calculation of frequencies, the total number of deliveries in the setting
      during the study period was used. All subjects underwent a complete obstetrical
      clinical workup comprising of history, general physical examination, abdominal
      and pelvic examination, relevant laboratory investigations. The maternal
      condition was assessed and managed according to established hospital protocols
      which included both pharmacological and surgical intervention. All maternal
      complications were noted and recorded on pre-designed proformas. Data was entered
      and analyzed by computer. RESULTS: A total of 50 cases of primary PPH were
      recorded during the study period. The frequency of PPH was calculated as 7.1%.
      The major cause of PPH was uterine atony found in 29 (58%) cases, followed by
      cervical, vaginal and perineal tears in 12 (24%) cases. Initially all patients
      were managed pharmacologically followed by surgical intervention. Subtotal
      (haemostatic) hysterectomy was performed in 10 (20%) cases. Maternal morbidity
      was detected in 31 (62%) of cases; the major morbidities were DIC in 3 (6%)
      cases, Acute renal failure in 3 (6%) patients and shock in 2 (9.9%) cases and
      anaemia in 20 (90.1%) cases. CONCLUSION: The study concludes that the frequency
      of primary PPH in this setting is in keeping with globally cited frequencies.
      Other findings such as causes of primary PPH and maternal morbidity data also
      agree with most national and international studies on this topic.

PMID- 19385461
TI  - Compliance to antihypertensive drugs, salt restriction, exercise and control of
      systemic hypertension in hypertensive patients at Abbottabad.
AB  - BACKGROUND: Hypertension is one of the most important cardiovascular risk factor
      but its control is still a challenge for physicians all around the world. Control
      of blood pressure can reduce cardiovascular morbidity and mortality, so the
      compliance to antihypertensive drugs and life style modification play an
      important role for the control of hypertension. This analytical (cross-sectional)
      study was conducted to assess prevalence of control of hypertension among
      hypertensive patients and to assess the relationship of control of hypertension
      with factors like compliance to antihypertensive drugs, salt restriction and
      exercise among the hypertensive patients. This study was conducted at outpatient
      clinic of medicine at Shahina Jamil Hospital Abbottabad from April 2007 to
      September 2007. METHODS: Eighty-nine patients seen in the outpatient clinic of
      medicine were enrolled in the study. All the patients with age 15 years or above,
      diagnosed as a case of systemic hypertension were included. RESULTS: Among eighty
      nine patients, 67 were female and 22 were male with mean age of 55.8 +/- 13.4
      years, mean systolic and diastolic blood pressure of 160 +/- 28.6 and 97.8 +/-
      14.1 mm Hg respectively, and pulse rate of 85.9 +/- 11.4 per minutes. Out of 89
      patients, 25.8% were having controlled hypertension, 48.3% were compliant and
      51.7% were not compliant to antihypertensive drugs, 55.1% were having salt
      restriction and 44.9% were having no salt restriction and 23.6% were used to do
      physical activity while 76.4% were not used to do physical activity. In group A
      consisted of patients with controlled hypertension, 95.7% patients were compliant
      to antihypertensive patients, 95.7% were having salt restriction, and 43.5% were
      used to do physical activity. In group B consisted of patients with uncontrolled
      hypertension, only 31.8% were compliant to antihypertensive drugs, 40.9% were
      having salt restriction, 16.7% were used to do physical activity. CONCLUSION:
      Hypertension can be controlled if the hypertensive patients have good compliance
      to antihypertensive drugs, salt restriction and do some sort of physical activity
      regularly and in this way, prevent themselves from the hypertensive
      complications.

PMID- 19385462
TI  - Association and pattern of diastolic dysfunction in patients of metabolic
      syndrome.
AB  - BACKGROUND: Diastolic dysfunction is important predictor of morbidity and
      mortality in patients with metabolic syndrome. This prospective study is to
      evaluate an association and pattern of diastolic dysfunction in patients of
      metabolic syndrome in our population. This cross-sectional study was performed at
      Armed Forces Institute of Cardiology Rawalpindi for a period of 6 months from
      20th November 2007 to 20th April 2008. METHODS: One hundred eligible and
      consenting patients having metabolic syndrome reporting in the OPD were
      registered. Inclusion criteria included patients of metabolic syndrome with
      negative ETT and normal systolic function. Exclusion criteria were patients with
      age above 60 years and valvular heart disease. Data was collected by a structured
      clinical interview with a physician, ECG and a transthoracic M-mode, 2D and TDI
      echocardiogram. The metabolic syndrome was defined according to International
      Diabetes Federation. RESULTS: There was a positive association between the degree
      of the metabolic syndrome-assessed as number of concurrently present components
      and parameters of cardiac structure and function, with a consistent and
      statistically significant trend for all cardiac variables considered (p = 0.000).
      There was also a positive association between each parameter and the cardiac
      diastolic dysfunction grading, e.g., systolic blood pressure (p = 0.000),
      diastolic blood pressure (p = 0.005), waist circumference (p = 0.004), fasting
      blood sugar (p = 0.008), triglycerides (p = 0.006), HDL cholesterol (p = 0.001).
      CONCLUSION: Several cardiac functional abnormalities regardless of symptoms
      increased progressively with increasing degree of metabolic syndrome.

PMID- 19385463
TI  - Surgical experience with cardiac myxomas.
AB  - BACKGROUND: Cardiac myxomas are the most common benign intracardiac tumours. We
      studied the clinical presentation of cardiac myxomas and the morbidity, mortality
      and recurrence rate following surgery at our institution over a 6 year period.
      METHODS: This historical longitudinal study was performed at department of
      Cardiac Surgery, Armed forces Institute of Cardiology and National Institute of
      Heart Diseases Rawalpindi, Pakistan between January 2002 and March 2008 a total
      number of 8506 cardiac operations were performed. Of these 34 patients (19 males,
      15 females) underwent complete excision of primary or recurrent intracardiac
      myxomas. Pre-operative diagnosis was established by echocardiography. All
      patients underwent operation soon after the diagnosis of a myxoma was made.
      Complete tumour excision followed by close inspection and copious saline
      irrigation of the cardiac chambers was done in each case. Of the 32 patients who
      survived the surgery, 29 patients were followed up at regular intervals for
      recurrence. The mean follow-up period was 34 months. RESULTS: Cardiac myxomas
      constituted 0.40% of the total cardiac operations at our institution. They most
      commonly occurred in the fourth decade. The commonest location was the left
      atrium (LA) (79%) followed by the right atrium (RA) (14%). Only one patient had
      myxoma in the right ventricle (RV). Patients with LA myxoma simulated mitral
      stenosis clinically whereas patients with RA and RV myxomas presented with
      features of right heart failure. A smaller percentage presented with embolic and
      constitutional symptoms. There were two early deaths. One recurrence was noted at
      27 months after surgery. No late deaths were observed in the study. CONCLUSION:
      Cardiac myxomas form a very small percentage of the cardiac cases. A high index
      of suspicion is essential for diagnosis. Echocardiography is the ideal diagnostic
      tool as also for follow-up. Immediate surgical treatment is indicated in all
      patients. Cardiac myxomas can be excised with a low rate of mortality and
      morbidity.

PMID- 19385464
TI  - Early vascular complications of intraaortic balloon counterpulsation in patients
      undergoing open heart surgery.
AB  - BACKGROUND AND OBJECTIVES: The use of IABP is helpful for haemodynamic stability
      of patients with low cardiac output and compromised left ventricular function in
      patients who undergo coronary artery bypass grafting. This procedure is also
      associated with some vascular complications due to the insertion of IABP. The
      objective of this research was to study the vascular complications in patients
      with IABP counterpulsation. We observed the clinical outcome of these patients
      with special reference to post IABP complications in our research. METHODS: One
      hundred and six consecutive patients were included in this study from August 2005
      to February 2007. Mean age of patients was 58.08 +/- 1.814 years. Seventy nine
      patients (74.5%) were male and 29 (25.5%) were females. Out of these 106
      patients, 101 were operated for CABG, one for angina due to aortic stenosis, two
      patients had ischemic mitral regurgitation and one patient had post infarct VSD.
      In 102 (96.2%) patients IABP was inserted percutaneously, one patient received
      transthoracic and in three patients IABP was inserted with open technique.
      Thirteen (12.3%) patients received IABP with sheath and 93 (87.7%) received IABP
      without sheath. RESULTS: Ten patients (9.4%) out of 106 developed vascular
      complications due to insertion of IABP. Seven patients (6.6%) had the major
      complications and 3 (2.8%) patients developed minor vascular complications.
      Mortality due to vascular complications in 106 patients was 8.49% with p < 0.005.
      CONCLUSION: IABP has remarkable beneficial effects in patients with haemodynamic
      instability due to myocardial ischemia and low cardiac output syndrome. At the
      same time IABP is related to significant morbidity and mortality related to
      vascular complications due to its insertion which include limb ischemia, limb
      loss and even mortality.

PMID- 19385465
TI  - Comparison of closed and open methods of pneumoperitonium in laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Pneumoperitonium is the first step in laparoscopic surgery including
      cholecystectomy. Two commonly used methods to create pneumoperitonium are closed
      and open technique. Both have advantages and disadvantages. The current study was
      designed to compare these two techniques in terms of safety and time required to
      complete the procedure. METHODS: This was a randomized controlled prospective
      study conducted at Department of Surgery, Ayub Hospital Complex Abbottabad, from
      1st June 2007 to 31st May 2008. Randomization was done into two groups randomly
      using sealed envelopes containing the questionnaire. Seventy envelopes were kept
      in the cupboard, containing 35 proformas for group A and 35 for group B. An
      envelope was randomly fetched and opened upon selection of the patient after
      taking the informed consent. Pneumoperitonium was created by closed technique in
      group A, and by open technique in group B. Time required for successful
      pneumoperitonium was calculated in each group. Failure to induce pneumoperitonium
      was determined for each technique. Time required to close the wounds at
      completion, total operating time and injuries sustained during induction of
      pneumoperitonium were compared in both techniques. RESULT: Out of the total 70
      patients included in study, 35 were in group A and 35 in group B. Mean time
      required for successful pneumoperitonium was 9.17 minutes in group A and 8.11
      minutes in group B. Total operating time ranged from 55 minutes to 130 minutes in
      group A and from 45 minutes to 110 minutes in group B. Mean of total operating
      time was 78.34 and 67 minutes in group A and B respectively. Mean time needed to
      close the wound was 9.88 minutes in group A and 4.97 minutes in group B. Failure
      of technique was noted in three patients in group A while no failure was
      experienced in group B. In two cases in group A minor complications during
      creation of pneumoperitonium were observed while in group B no complication
      occurred. No patient died in the study. CONCLUSIONS: We concluded from this study
      that open technique of pneumoperitonium was, less time consuming and safer than
      the closed technique.

PMID- 19385466
TI  - Carcinoma of prostate in clinically benign enlarged gland.
AB  - BACKGROUND: Carcinoma of the prostate is one of the common tumours of old age in
      men. This cross sectional study was conducted to detect carcinoma of prostate in
      clinically benign enlarged gland and to evaluate the efficacy of Digital rectal
      Examination in detection of prostatic cancer in patients presented at Khyber
      Teaching Hospital, Peshawar from July 1998 to July 1999. METHODS: Patients
      presenting with lower urinary tract symptoms over the age of 50 years were
      evaluated on English version of International Prostate Symptoms Score (IPSS),
      clinically examined and post-voiding residual urine determined on abdominal
      sonography. The selection criteria were; Severe IPSS, absence of signs of
      malignancy on Digital Rectal Examination (DRE) and post-voiding residual urine
      more than 100 ml. Thus a total 100 patients were selected for further study. Four
      ml blood was taken to assess Prostate Specific Antigen (PSA) level pre
      operatively. All these patients underwent either transvesical prostatectomy or
      transurethral resection of prostate (TURP) and enucleated prostatic tissues were
      sent to histopathology. RESULTS: Eighty-five percent patients had PSA level up to
      10 etag/ml. PSA level of 15 (15%) patients were above 10n gm/ml out of which 13
      (13%) patients were having PSA in range of 11-12 etag/ml and two (2%) had PSA
      level between 20-25 etag/ml. Histopathology report of 2% patients turned out as
      adenocarcinoma of the prostate. CONCLUSION: Out of 100 patients who were having
      clinically benign DRE findings, 2 turned out as Carcinoma of the prostate
      histologically.

PMID- 19385467
TI  - Aspiration and tetracycline sclerotherapy of primary vaginal hydrocoele of testis
      in adults.
AB  - BACKGROUND: Primary Vaginal Hydrocoele of Testis is a common condition which is
      primarily treated surgically. Many patients with Hydrocoele of testis are either
      not willing or are unfit for surgery. This study was done to know the safety,
      efficacy and out come of tetracycline induced sclerotherapy of Primary Vaginal
      Hydrocoele of Testis in adults. METHODS: This quasi experimental study was done
      in Shahina Jamil Hospital, attached with Frontier Medical College and Ayub
      Teaching Hospital, Abbottabad from March 2006 to April, 2007. Thirty-seven
      patients with primary vaginal hydrocoele were included in the study. Aspiration
      and instillation of Tetracycline was done after spermatic cord block with 2%
      lignocaine. Procedure time, Peri and Post-procedure complications, number of
      injections for cure and patients' satisfaction with the procedure were recorded.
      Patients were discharged home 3 to 4 hours after the procedure and followed up
      after one week, one month, three months and six months. Direct admission and re
      admissions were recorded. RESULTS: The mean age of patients was 47 years. Mean
      procedure time was 45 minutes. All patients were cured. Mild postoprocedure pain
      occurred in 12 (40%), moderate pain in 14 (46%) patients and severe pain in 4
      (13.3%) patients. No patient developed haematoma or local infection. One patient
      (3.3%) had micturition problem. Two (6.6%) patients had minimal recurrence. One
      injection was sufficient for cure in all patients. 28 (93%) patients were
      satisfied while 2 (6.6%) patients were not satisfied with this procedure. No
      patient was admitted in the hospital after the procedure. CONCLUSION: Aspiration
      and injection of tetracycline in Primary vaginal Hydrocoele of Testis in adults
      is safe, effective and very economical procedure.

PMID- 19385468
TI  - Mortality in necrotizing fasciitis.
AB  - OBJECTIVE: The objective of this study was to determine the mortality rate in
      patients presenting with Necrotizing Fasciitis. This prospective study was
      conducted at ward 26, JPMC Karachi over a period of two years from March 2001 to
      Feb 2003. METHODS: All patients above the age of 12 years diagnosed to be having
      Necrotizing Fasciitis and admitted through the Accident and emergency department
      were included in this study. After resuscitation, the patients underwent the
      emergency exploration and aggressive surgical debridement. Post-operatively, the
      patients were managed in isolated section of the ward. The patients requiring
      grafting were referred to plastic surgery unit. The patients were followed up in
      outpatients department for about two years. RESULTS: Over all, 25 male and 5
      female patients fulfilled the inclusion criteria and were included in this study.
      The common clinical manifestations include redness, swelling, discharging
      abscess, pain, fever, skin necrosis and foul smelling discharge etc. The most
      common predisposing factor was Diabetes mellitus whereas the most commonly
      involved site was perineum. All patients underwent aggressive and extensive
      surgical debridements. The common additional procedures included Skin grafting,
      Secondary suturing, Cystostomy and Orchidectomy. Bacteroides and E. coli were the
      main micro-organisms isolated in this study. Bacteroides was the most common
      microorganism isolated among the eight patients who died. CONCLUSION: Necrotizing
      Fasciitis is a potentially life threatening emergency condition and carries the
      mortality rate of about 26.6%. The major contributing factors to increase the
      mortality missed initially diagnosed, old age, diabetes mellitus truncal
      involvement and late presentation. Anorectal involvement of disease carry worse
      prognosis. Hyperbaric oxygen therapy and proper use of unprocessed honey reduced
      the mortality rate.

PMID- 19385469
TI  - Mushroom poisoning in children: clinical presentation and outcome.
AB  - BACKGROUND: A variable clinical picture characterizes mushroom poisoning. The
      Amatoxin, the main toxic component of these fungi, are responsible for
      gastrointestinal symptoms as well as hepatic and renal failure. As acute
      gastroenteritis is extremely common in our set up, so every patient presenting
      with these symptoms is treated as gastroenteritis of viral aetiology. The authors
      present the clinical picture of the phalloid syndrome, its treatment and
      immediate outcome. METHODS: All children age less than 16 years admitted in Saidu
      Hospital Swat from January to December 2006 with mushroom poisoning were included
      in the study. Patients with doubtful history or with associated illness were not
      included. The diagnosis was based on the clinical picture of the patient, history
      and the laboratory data. In addition to maintenance of fluid and electrolyte
      balance and treating sepsis, oral Silymarin and intravenous penicillin was
      started. Liver function tests, renal functions tests, serum electrolytes and
      coagulation profile was done in all the patients. The severity of poisoning was
      graded according to hepatic transaminase elevations and prolongation of
      prothrombin time. RESULTS: Of the 18 patients, fifteen were above five years of
      age. Female were twice in number. Fifteen patients developed hepatic failure and
      three patients developed renal failure. Thirteen patients expired. CONCLUSION: To
      start timely management, Mushroom poisoning should be considered in the
      differential diagnosis in patients presenting with food poisoning particularly
      coming in groups. Delay in diagnosis is associated with high mortality.

PMID- 19385470
TI  - Morbidity & mortality of firearm injury in Peshawar Region.
AB  - BACKGROUND: Firearm injuries cause significant morbidity and mortality among its
      victims. The present study, carried out at a major tertiary care hospital of
      Peshawar, Pakistan was aimed at highlighting the extent and severity of firearm
      related morbidity and resultant mortality despite expert medical care. METHODS:
      All victims of firearm injury brought to the Lady Reading Hospital Peshawar
      Emergency Department and thereafter admitted to hospital wards during the period
      mid-2006 to mid-2007 were included in the study prospectively regardless of age,
      gender or socio-economic status. Data relevant to the background of firearm use,
      type of firearm used, types and extents of injuries, clinical condition of the
      patients and final outcome were collected on performas and entered into SPSS 15.0
      for analysis. RESULTS: Seventy-four cases of firearm injury were recorded during
      the study period, with a predominant male to female ratio (9.6:1). Most victims
      (79.7%) were in the age group of 15-35 years. Although there were more cases from
      Peshawar (28.4%), there was no major referral pattern noted. High velocity
      weapons were used in 95.9% of cases and homicide was the main motive for injury
      (60.8%). Injuries were sustained most frequently in the abdomen and pelvis
      (44.6%) and 67.6% of victims sustained internal injuries. There were only 5
      (6.8%) deaths from firearm injuries. CONCLUSION: It is concluded, the young males
      of the population must be targeted for lifestyle adjustments such as training to
      refrain from anger or disputes (usually over petty things) and to prevent the
      easy access of firearms as a weapon to settle disputes.

PMID- 19385471
TI  - Vascular endothelial growth factor and basic fibroblast growth factor expression
      positively correlates with angiogenesis and peritumoural brain oedema in
      astrocytoma.
AB  - BACKGROUND: Astrocytoma is the most malignant intracranial neoplasm and is
      characterized by high neovascularization and peritumoural brain oedema.
      Angiogenesis is a complicated process in oncogenesis regulated by the balance
      between angiogenic and antiangiogenic factors. METHODS: The expression of two
      angiogenic growth factors, vascular endothelial growth factor and basic
      fibroblast growth factor were investigated using immunohistochemistry for
      astrocytoma from 82 patients and 11 normal human tissues. RESULTS: The expression
      of vascular endothelial growth factor and basic fibroblast growth factor
      positively correlate with the pathological grade of astrocytoma, microvessel
      density numbers and brain oedema, which may be responsible for the increased
      tumour neovascularization and peritumoural brain oedema. CONCLUSION: The results
      support the idea that inhibiting vascular endothelial growth factor and basic
      fibroblast growth factor are useful for the treatment of human astrocytoma and to
      improve patient's clinical outcomes and prognosis.

PMID- 19385472
TI  - Morphological changes in human placenta of wet snuff users.
AB  - BACKGROUND: Wet snuff is commonly used by both males and females in different
      parts of Pakistan. Apart from other ingredients, tobacco is the major component
      of snuff. Adverse effects of smoking on morphology of human placenta have been
      shown by some previous studies. But snuff is not considered as dangerous as
      smoking during pregnancy. This study was designed to see the effects of snuff on
      morphology of human placenta. METHODS: In present study total 80 human placentae,
      40 from normal and 40 from snuff users were used. This study was carried out in
      the Department of Anatomy Basic Medical Sciences Institution (BSMI) Karachi.
      Duration of study was six months. Samples were obtained from Gynaecology and
      Obstetric unit-I JPMC. Placentae washed well with running tap water to remove
      blood clots. Umbilical cord and other membranes were removed and placenta gently
      squeezed to expel the foetal blood. Gross features like weight, diameters,
      central thickness and attachment of umbilical cord were noted in normal and snuff
      users' placentae. Then placentae were preserved in 10% formalin for at least five
      days before the sectioning for micromorphology. Placentae divided in two groups-A
      & B. 4 microm thick sections of the tissue were taken on rotary microtome and
      stained with H & E, Mallorys trichrome and methanamine silver for different
      histological observations. RESULTS: Micromorpholgical changes have been observed
      in placentae of snuff users leading to loss of functional components of
      placentae. This loss of functional component may have deleterious effects on
      outcome of pregnancy. No significant gross morphological changes were found in
      snuff user placentae. CONCLUSION: Wet snuff effect the micromorphology of
      placenta leading to loss of functional component and in turn effects the exchange
      of materials between mother and foetus which may leads to intrauterine growth
      retardation. Loss of trophoblasts may lead to hormonal imbalance necessary for
      normal pregnancy and this imbalance can cause premature labour. Nocotine can
      cross the placental barrier, which may produce foetal tachycardia.

PMID- 19385473
TI  - Gender differences on bioavailabity of ofloxacin.
AB  - BACKGROUND: The fluoroquinolones are currently enjoying extensive worldwide
      clinical applications because of their good bioavailability and pharmacokinetic
      profile. Investigation into several aspects of the pharmacokinetic of all
      clinically relevant fluoroquinolones, have been carried out notably in Europe,
      USA and Japan. In view of the 'geonetical' (geographical influences on genetics
      pharmacogenetics) differences, it is important that for the optimal therapeutic
      outcome, biodisposition studies on drugs are better conducted in the population
      and environments where wide and extensive use of the drug is anticipated. The
      Objectives of study were to see the pharmacokinetic parameters in healthy young
      male and female volunteers. This comparative study was conducted King Edward
      Medical University, Lahore, Pakistan, from July 2005 to December 2005. METHOD: In
      Pakistan where the use of antibiotics is more frequent by the general
      practitioners it is important to elucidate certain dose parameters it is also
      noticed that side effects are more in females than males so present study is
      conducted to calculate any differences in bioavailability on the basis of sex.
      The pharmacokinetic parameters of ofloxacin were determined in each of the
      clinically health eight young girls and boys (mean age 23.9 and 25.1 years,
      respectively) following a single oral dose of 400 mg tablet. The method adopted
      was microbiological assay. RESULTS: The blood samples collected at predetermined
      time intervals after drug administration revealed almost twice as high
      concentration of the drug in plasma of the girls than that in the boys. The
      pharmacokinetic parameters revealed significantly (p < 0.01) higher values for
      area under curve (AUC) and C(max) and lower total body clearance (TBC) and volume
      of distribution in the girls than in the boys. CONCLUSION: The gender differences
      in pharmacokinetic parameters indicate that the dose adjustment should be
      considered in male and female.

PMID- 19385474
TI  - A new and novel treatment of opioid dependence: Nigella sativa 500 mg.
AB  - BACKGROUND: Opioid dependence is one of the major social and psychiatric problem
      of society. Unfortunately there is no non opiate treatment available. For
      centuries man has used plants for their healing proprieties. These plants play a
      fundamental part in all treatment modalities, both ancient and modern. METHODS:
      This study was conducted to find non opiate treatment for opiate withdrawal.
      Total 35 known addicts of opiates were included in the study. This study was
      based on DSM IV criteria for opioid dependence. RESULT: This study demonstrates
      that non opioid treatment for opioid addiction decreases the withdrawal effects
      significantly. It further demonstrates that there are no changes in physiological
      parameters of subjects during treatment (BP, Pulse rate etc.). There is increased
      appetite but no significant weight gain in the subjects. CONCLUSION: Non opioid
      drug Nigella sativa is effective in long-term treatment of opioid dependence. It
      not merely cures the opioid dependence but also cures the infections and weakness
      from which majority of addicts suffer.

PMID- 19385475
TI  - Key to successful vesico-vaginal fistula repair--an experience of urogenital
      fistula surgeries and outcome at gynaecological surgical camp-2005.
AB  - BACKGROUND: Vesico-vaginal fistula is not life threatening medical problem, but
      the woman face demoralization, social boycott and even divorce and separation.
      The aetiology of the condition has been changed over the years and in developed
      countries obstetrical fistula are rare and they are usually result of
      gynaecological surgeries or radiotherapy. Urogenital fistula surgery doesn't
      require special or advance technology but needs experienced urogynaecologist with
      trained team and post operative care which can restore health, hope & sense of
      dignity to women. METHODS: This prospective study was carried out to analyze the
      success rate in patients attending the referral hospital and sent from free
      gynaecological surgery camps held at interior of Sindh, and included preoperative
      evaluation for route of surgery, operative techniques and postoperative care.
      Total 70 patients were admitted from the patients attending the camp. Out of
      these, 29 patients had uro-genital fistula. Surgical repair of the fistula was
      done through vaginal route on 27 patients while 2 required abdominal approach.
      RESULTS: Out of 29 surgical repairs performed, 27 proved successful. CONCLUSION:
      Difficult and complicated fistulae need experienced surgeon. Establishment of
      separate fistula surgery unit along with appropriate care and expertise accounts
      for the desired results.

PMID- 19385476
TI  - Branch retinal vein occlusion.
AB  - Retinal vein occlusions (RVO) are the second commonest sight threatening vascular
      disorder. Branch retinal vein occlusion (BRVO) and central retinal vein occlusion
      (CRVO) are the two basic types of vein occlusion. Branch retinal vein occlusion
      is three times more common than central retinal vein occlusion and- second only
      to diabetic retinopathy as the most common retinal vascular cause of visual loss.
      The origin of branch retinal vein occlusion undoubtedly includes both systemic
      factors such as hypertension and local anatomic factors such as arteriovenous
      crossings. Branch retinal vein occlusion causes a painless decrease in vision,
      resulting in misty or distorted vision. Current treatment options don't address
      the underlying aetiology of branch retinal vein occlusion. Instead they focus on
      treating sequelae of the occluded venous branch, such as macular oedema, vitreous
      haemorrhage and traction retinal detachment from neovascularization. Evidences
      suggest that the pathogenesis of various types of retinal vein occlusion, like
      many other ocular vascular occlusive disorders, is a multifactorial process and
      there is no single magic bullet that causes retinal vein occlusion. A
      comprehensive management of patients with retinal vascular occlusions is
      necessary to correct associated diseases or predisposing abnormalities that could
      lead to local recurrences or systemic event. Along with a review of the
      literature, a practical approach for the management of retinal vascular
      occlusions is required, which requires collaboration between the ophthalmologist
      and other physicians: general practitioner, cardiologist, internist etc. as
      appropriate according to each case.

PMID- 19385477
TI  - Mesenteric volvulus in children: two autopsy cases and review of the literature.
AB  - Small bowel mesenteric volvulus when compared with mesocolonic volvulus, have not
      high incidence. Two autopsy cases of small bowel mesenteric volvulus in infants,
      highlighting the importance of a suspicion in early recognition of this rare but
      potentially fatal intra-abdominal emergency are reported. We also review the
      literature on possible aetiologies and mechanism of small bowel mesenteric
      volvulus, as well as its management.

PMID- 19385478
TI  - Small bowel perforations due to deliberate ingestion of injurious foreign bodies-
      a personal experience.
AB  - Ingestion of foreign bodies is not an uncommon problem in our society. The
      patients usually ingest different types of foreign bodies either accidentally or
      deliberately. Rare in children but adults are not uncommonly affected and are
      either psychiatric patients or ingest foreign bodies accidentally. Life
      threatening complications may occur at times due to ingestion of sharp and
      pointed objects. An interesting case of ingestion of multiple injurious foreign
      bodies presenting with multiple small intestinal perforations is presented with
      review of literature.

PMID- 19385480
TI  - Mucoepidermoid carcinoma of parotid presenting as unilocular cyst.
AB  - An interesting case of a 09 years old girl is reported who presented with a
      painless, mobile, spherical, fluctuant and brilliantly translucent swelling in
      front of left ear. The fine needle aspiration revealed turbid dark yellow colour
      fluid. This cystic swelling was completely excised and the specimen on
      histopathology was reported as low grade Mucoepidermoid carcinoma. Recovery was
      uneventful. This unusual presentation of Mucoepidermoid carcinoma as a
      preauricular cyst is one of the rare unique reported case.

PMID- 19385479
TI  - Combined urethrolithotomy with vesicolithotomy in an 18-months old boy.
AB  - We present a case of 18 months old male child who reported with acute urinary
      retention. He had a urethral calculus along with a vesical calculus. He was
      subjected to combined external urethrotomy and open vesicolithotomy in one
      sitting. The patient made a smooth post operative recovery and was followed up
      for 6 months.

PMID- 19385481
TI  - N-butyl-2-cyanoacrylate and lipoidol pulmonary embolism (glue embolism).
AB  - Glue embolisation is a rare happening and many clinicians who evaluate patients
      for post sclerotherapy problems may be unaware of this complication. We present a
      case of pulmonary embolism in a patient of cirrhosis liver secondary to gastric
      variceal sclerotherapy with N-Butyl-2-cyanoacrylate and lipoidol solution. This
      is also called glue embolism.

PMID- 19385482
TI  - Data analysis workshops to enhance analytical skills among health professionals:
      an experience of conducting workshop with hands-on training on SPSS.

PMID- 19385484
TI  - Stem cell transplantation in Malaysia and future directions.

PMID- 19385483
TI  - Anaesthesia for interventional neuroradiology.

PMID- 19385485
TI  - Adult allogeneic haematopoietic stem cell transplantation: a single centre
      experience in Malaysia.
AB  - We analysed the outcome of 104 patients from a single institution who underwent
      allogeneic haematopoietic stem cell transplantation (AHSCT) from their HLA
      identical siblings between 1993 and 2006. Sixty-nine percent of patients had
      peripheral blood stem cell (PBSC) as the stem cell source and the remaining had
      bone marrow (BM). The majority of patients are Chinese (60%) followed by Malays
      (24%) and Indians (14%). The median time to reach white cell counts of >1 x
      10(9)/L and platelet counts of >30 x 10(9)/L was 13 and 15 days, respectively in
      patients who had PBSC transplantation compared with 16 and 25 days in patients
      who had BM transplantation, (p < 0.0001 and p < 0.001). Acute graft-versus-host
      disease (aGVHD) of grade II to IV was observed in 34% of patients and chronic
      graft-versus-host disease (cGVHD) in 38% of patients. Although not statistically
      significant, there was a higher incidence of overall aGVHD in Indian patients
      (73%) compared to Chinese and Malays (57% and 56% respectively). There was no
      significant difference in the incidence of aGVHD and cGVHD with the source of
      stem cells. Overall survival (OS) and disease free survival (DFS) was 50% and 60%
      at five years respectively. Multivariate analysis showed that patients
      transplanted in standard risk and those who had limited cGVHD had a significant
      better OS, (p = 0.05 and p = 0.05). Patients who had cGVHD and transplanted in
      standard risk had a better DFS, (p = 0.002 and p < 0.001). In summary, AHSCT in
      standard risk patients is associated with a better outcome than those
      transplanted in high risk and although not statistically significant, there is a
      higher incidence of aGVHD in Indian patients.

PMID- 19385486
TI  - Improvements of knowledge and perception towards HIV/AIDS among secondary school
      students after two hours talk.
AB  - Malaysia is confronted with an increasing incidence of HIV and AIDS among
      adolescents and young adults. The effectiveness of various programs offered to
      school going teenagers is unknown. The objective of this study is to measure the
      effectiveness of two hours talk on sex education offered by a non governmental
      organization (NGO) in improving youngsters' knowledge and perception towards HIV
      and AIDS. A cross sectional study was conducted among the adolescent students
      from a secondary school in Ipoh, Perak, a province of Malaysia. A total of 182
      students participated in the study. A standard questionnaire consisting of
      demographic data, knowledge and perception towards HIV/ADIS were distributed
      before (pre-test) and after the intervention (post-test). Performance of
      participants was compared to establish the effectiveness of the intervention. Our
      findings suggests that there was a significant increase in participants'
      knowledge and perception after the intervention (p = 0.000). Knowledge
      improvement was found in both genders however, improvement in perception was
      higher among female students. Interestingly, 80% of participants disagree that
      sexual education will encourage sex among youngsters. NGOs are playing a
      supplementary role in providing sex education programs in schools. This program
      although of short duration but it is effective in enhancing adolescence awareness
      about HIV/AIDS.

PMID- 19385487
TI  - Benefit and pitfalls of newborn hearing screening.
AB  - The importance of universal newborn hearing screening (UNHS) in identifying
      hearing-impaired infants as early as possible is already well recognized.
      Transient evoked otoacoustic emissions (TEOAE) have been established as a
      reliable method for UNHS in full term infants. This is a cross sectional study
      between April 2003--December 2005. Thirteen thousand five hundred and ninety
      eight (13,598) newborns were screened for hearing loss with portable otoacoustic
      emission (OAE) before discharge. The initial coverage rate during the 3 years
      study period was 85.9% (13,598) with 89.2% (3762), 79.0% (4480) and 90.3% (5356)
      for 2003, 2004 and 2005 respectively. The mean age when hearing loss was
      diagnosed using ABR were 3.56 months old, 3.08 months old, and 2.25 months old
      and 3.01 months old for 2003, 2004, 2005 respectively and it was statistically
      significant. The defaulter rate at the third stage during the 3 years study
      period was 35% (21), 15.2% (7) and 18.2% (2) for 2003, 2004 and 2005
      respectively. This study showed significant improvement in initial referral rate,
      coverage rate and age of diagnosis. However, we need to improve on high defaulter
      rates.

PMID- 19385488
TI  - Medical thoracoscopy: Pahang experience.
AB  - Medical thoracoscopy has gain its popularity in Malaysia recently. This paper
      presents our early experience in thoracoscopy using semi-rigid fiberoptic
      thoracoscope. All thoracoscopy records since October 2006 were retrieved. The
      patients' records, thoracocentesis investigations results, thoracoscopic findings
      and all pleural biopsy results were reviewed. Twenty-four thoracoscopic
      procedures on 22 patients in whom two patients had repeated thoracoscopy. Ten
      patients were confirmed carcinoma. Eight patients had inconclusive thoracoscopic
      pleural biopsy results. Three patients underwent pleurodesis for malignant
      effusion. One patient had adhesiolysis for empyema. There was no procedure
      related deaths or intraoperative accidents. Thoracoscopy is a relatively safe
      procedure.

PMID- 19385489
TI  - Awareness on ex-gratia compensation scheme among medical department staff in a
      tertiary government hospital in Kuala Lumpur.
AB  - The Ex-Gratia Compensation Scheme was introduced by the Government of Malaysia in
      1994 to provide compensation, which is not covered by any prior legislation, for
      all its workers suffering from injuries and illnesses due to work. Despite more
      than ten years of implementation, the submission for claims is still minimal and
      there is an impression that awareness on the provision of Ex-Gratia benefit among
      government employees, especially health care staff, is poor. A cross sectional
      survey was conducted at a medical department of a government hospital in Kuala
      Lumpur to assess the knowledge and awareness level on Ex-Gratia among a
      representative group of front line health care workers. The results show that the
      respondents' knowledge on Ex-Gratia is generally poor as compared to knowledge on
      the Social Security (SOCSO) Schemes. Majority of the respondents are unsure
      whether they will be compensated in case of occupational illness and injuries.
      They also do not know what kind of compensation scheme they are currently
      eligible. There is an urgent need for the Treasury and health care managers to
      expand the knowledge and awareness on Ex-Gratia among health care workers.

PMID- 19385490
TI  - Risk factors associated with low birth weight infants in the Malaysian
      population.
AB  - This study aimed to identify the risk factors which were significantly associated
      with low birth weight (LBW, <2500 g) infants among the Malaysian population. This
      was a case-control study carried out at the Tuanku Jaafar Hospital, Seremban,
      Malaysia over a five-month period. Cases were all infants born with birth weight
      less than 2500 g. Control infant were selected with the help a random sampling
      table from among infants with birth weight of > or =2500 g born on the same day
      in the hospital. Of 3341 livebirths delivered in the hospital, 422 (12.6%) were
      LBW infants. Logistic regression analysis showed that, after controlling for
      various potential confounders, the only significant risk factors associated with
      infants of LBW were gestational age (adjusted odds ratio (OR)=0.6, 95% C.I.: 0.5,
      0.6; < 0.0001), maternal pre-pregnancy weight (adjusted OR = 0.97, 95% C.I.:
      0.95, 0.99; p < 0.0001), nulliparity (adjusted OR = 3.4, 95% C.I.: 2.2, 5.1; p <
      0.0001), previous history of LBW infants (adjusted OR = 2.3, 95% C.I.: 1.4, 3.8;
      p=0.001) and PIH during current pregnancy (adjusted OR=3.3, 95% C.I.: 1.6, 6.6; p
      = 0.001). A number of potentially preventable or treatable risk factors were
      identified to be associated with LBW infants in Malaysia.

PMID- 19385492
TI  - The effect of "group detailing" on drug prescribing in primary care.
AB  - The quality of physician prescribing is suboptimal. Patients are at risk of
      potentially adverse reaction because of inappropriate or writing error in the
      drug prescriptions. We assess the effect of "group academic detailing" to reduce
      writing drug name using brand name and short form in the drug prescriptions in a
      controlled study at two primary health care clinics in Negeri Sembilan. Five
      medical officers in Ampangan Health Clinic received an educational intervention
      consisting of group academic detailing from the resident Family Medicine
      Specialist, as well as a drug summary list using generic names. The academic
      detailing focused on appropriate prescribing habit and emphasized on using the
      full generic drug name when writing the drug prescription. Analyses were based on
      3371 prescriptions that were taken from two clinics. The other health clinic was
      for comparison. The prescribing rates were assessed by reviewing the
      prescriptions (two months each for pre- and post-intervention phase).
      Statistically significant reduction in writing prescription using brand name and
      using short form were observed after the educational intervention. Writing
      prescription using brand name for pre- and postintervention phase were 33.9% and
      19.0% (postintervention vs pre-intervention RR 0.56, 95% CI 0.48 to 0.66) in the
      intervention clinic. Prescription writing using any short form for pre- and post
      intervention phase were 49.2% and 29.2% (post-intervention vs pre-intervention RR
      0.59, 95% CI 0.53 to 0.67). This low cost educational intervention focusing on
      prescribing habit produced an important reduction in writing prescription using
      brand name and short form. Group detailing appears to be feasible in the public
      health care system in Malaysia and possibly can be used for other prescribing
      issues in primary care.

PMID- 19385491
TI  - The outcome of pleomorphic sarcoma at University Malaya Medical Center--a fifteen
      year review.
AB  - Pleomorphic sarcoma is the most common sarcoma. Reports of outcome as well as
      evaluation of prognostic factors in the literature show great variation. We
      looked at our experience in treating this tumour at University Malaya Medical
      Center. This is a review of patients diagnosed with Pleomorphic Sarcoma from
      January 1990 to December 2005 at University Malaya Medical Center. Outcome
      measures studied are the overall survival, disease free survival and local
      recurrence of disease. Prognostic factors for survival and local recurrence which
      were studied are the tumour size, depth, stage, type of surgery, adjuvant
      therapy, and surgical margin. There were fifty four patients available for
      analysis of demographics. The mean age at presentation was 52.3 +/- 16.7 years.
      There were thirty male patients (56%) and twenty four female patients (44%) in
      the study population. The patients were predominantly Malay (44.4%) and Chinese
      (42.6%). There were two Indian patients (3.7%) and five patients from other races
      (9.3%). Thirty patients had disease affecting the extremities while six patients
      had disease affecting the trunk. Patients with tumour affecting the trunk had
      100% mortality. In patients with tumour affecting the extremity, 46.7% presented
      with Stage 3 disease. The overall median survival was 39 months. The overall
      survival rate at 3 years was 53.3% and the 5 years was 30.0%. The disease free
      survival rate at five years was 27.6%. However, if patients who presented with
      metastasis were excluded, the 5 year survival rate was 60% while the disease free
      survival was 53.3%. Recurrence rate was 33.3%. Factors affecting survival was
      stage, size and location of tumour. No factors were found to correlate with
      higher local recurrence rate. In conclusion, Pleomorphic Sarcoma is a
      heterogenous disease with variable outcome. In our centre, late presentation with
      advanced disease significantly affects the overall outcome of this condition.
      Tumour size and location are important prognostic factors. Inherent tumour
      behavior and aggressiveness probably outweigh current treatment modalities as the
      most important prognostic factor in the management of Pleomorphic Sarcoma.

PMID- 19385493
TI  - Long term Tai Chi exercise reduced DNA damage and increased lymphocyte apoptosis
      and proliferation in older adults.
AB  - Effect of Tai Chi exercise on the level of DNA damage using the comet assay,
      lymphocyte viability and frequency of sister chromatid exchange (SCE) were
      determined in adults aged above 45. Tai Chi participants of 7 years (n=35),
      showed higher level of normal DNA and lower level of mild and severely damaged
      DNA as compared to the sedentary subjects (n=35). The former are suggested to
      have effective DNA repair mechanism as their frequency of SCE was markedly lower.
      Higher lymphocyte apoptosis and proliferation found in the Tai Chi participants
      also indicated that the exercise promotes renewal and regeneration of
      lymphocytes.

PMID- 19385494
TI  - Audit of newborn screening programme for congenital hypothyroidism.
AB  - Newborn screening for congenital hypothyroidism (CH) was implemented in Hospital
      UKM in December 2004 using cord blood sample. From the audit over a period of 25
      months, a total of 13,875 newborn babies were screened with a coverage of 98.8%.
      From this cohort, the mean recall rate was 0.32%; unfortunately the mean
      percentage of recalled babies that came for retesting was only 79.5%. In
      addition, the mean sample rejection rate was high, i.e. 2.2%. Two babies were
      diagnosed to have CH. These findings implied that whilst the coverage of
      screening was good, there is a need for regular surveillance of performance of
      both clinical and laboratory personnel. In addition, a more concerted effort
      should be carried out to promote community awareness of such a programme.

PMID- 19385495
TI  - Angiokeratoma corporis diffusum.
AB  - Angiokeratoma is a dark violaceous keratotic papule which can be solitary or
      multiple. Generalised systemic angiokeratoma constitute angiokeratoma corporis
      diffusum, a rare X-linked recessive inborn error of glycosphingolipid metabolism
      due to deficiency of alpha galactosidase A. Patients with this disease have
      premature death due to the vascular complications. A case of possible Fabry's
      disease is presented.

PMID- 19385496
TI  - A case of cutaneous larva migrans acquired from soiled toilet floors in urban
      Kuala Lumpur.
AB  - Despite being a common skin dermatosis in the tropics, physicians in the tropics
      may miss the diagnosis of cutaneous larva migrans for other pruritic skin
      manifestation. This is especially in those who live in urban housing with no
      history of travel. Cutaneous larva migrans, an intensely pruritic skin pathology
      is mainly contracted by people with history of beach holiday or contact with
      moist soft sand which had been contaminated with dog or cat faeces. This article
      reports a patient who presented with intensely itchy papular spots over the
      dorsum of his foot after walking barefooted in an urban toilet soiled with cat
      faeces. The patient had initially seen an urban general practitioner who
      diagnosed the papular skin lesion as an allergic reaction, and prescribed
      antihistamines. The patient subsequently developed creeping skin lesions and was
      seen by the author who prescribed albendazole 400 mg twice daily for three days.
      The patient reported reduction in itching after two days of albendazole treatment
      and a follow up at ten days revealed a healed infection.

PMID- 19385497
TI  - An arrow in the maxillary sinus.
AB  - We experienced the case of a patient who had a foreign body in the maxillary
      sinus. The foreign body was an arrow accidentally triggered by the patient while
      fishing. The foreign body was removed via the Caldwell-Luc approach.

PMID- 19385498
TI  - Endoscopic resection of primary nasoseptal chondrosarcoma.
AB  - Chondrosarcoma of the nasal septum is an extremely rare malignant tumor. It
      accounts for only 10% to 20% of primary bone tumors, with approximately 10% found
      in the head and neck. A case is presented here to illustrate its presentation,
      evaluation and surgical treatment.

PMID- 19385499
TI  - Endoscopic orbital decompression for optic neuropathy in thyroid ophthalmopathy.
AB  - Optic neuropathy, an uncommon manifestation occurs in 5% of patients with Graves'
      ophthalmopathy. Its outcome is good if early and proper treatment given. We
      reported a 49 years old male patient of Graves' disease with bilateral optic
      neuropathy. He underwent bilateral transnasal endoscopic orbital decompression
      with marked improvement of visual acuity bilaterally. The preoperative visual
      acuity was 6/36 in his right eye and 6/60 in his left eye. Two days after
      operation, his visual acuity was 6/12 in his right eye and 6/24 in his left eye.
      Transnasal endoscopic orbital decompression is a choice of treatment in optic
      neuropathy in thyroid ophthalmopathy after trial of corticosteroids.

PMID- 19385500
TI  - The use of paramedian forehead flap reconstruction after wide excision of basal
      cell carcinoma of the nose.
AB  - Basal cell carcinoma (BCC) is an indolent, slow-growing malignant skin tumour.
      Approximately 70% of the tumours occur in the head and neck region. The nose is a
      common site for malignant skin tumours, such as basal cell carcinoma and squamous
      cell carcinoma because it is exposed to the sun. Excision of the BCC will leave
      the nose with a soft tissue defect which requires reconstruction. This report
      illustrates a case of BCC of nose whereby a wide excision and reconstruction was
      performed with a paramedian forehead flap.

PMID- 19385501
TI  - Cerebrospinal fluid rhinorrhoea secondary to amyloidosis of the sphenoid sinus.
AB  - Amyloidosis of the skull base is a rare entity. A patient with localized
      amyloidosis of the sphenoid sinus presented at our institution with cerebrospinal
      fluid rhinorrhoea. Endoscopic excision of the lesion and multilayered
      obliteration of the sphenoid sinus resolved the symptoms.

PMID- 19385502
TI  - Two stage penile reconstruction with free prefabricated sensate radial forearm
      osteocutaneous flap.
AB  - Penile reconstructive surgeries are performed mainly as radical treatment for
      conditions associated with congenital abnormalities of the urethra or penis,
      after penile trauma, penile cancer, short penis, corporal fibrosis and in cases
      of gender reassignment. We present here a method of penile reconstruction with a
      pre fabricated radial forearm free flap incorporating the segment of the radius
      for structural support.

PMID- 19385503
TI  - Recurrent Chromobacterium violaceum infection in a patient with chronic
      granulomatous disease.
AB  - We report a rare case of recurrent infection of Chromobacterium violaceum in an
      immunocompromised patient. Despite the high mortality rate associated with this
      infection as reported in the literature, this patient survived three episodes of
      recurrent infection. We believe that with high clinical suspicion, prompt
      treatment and appropriate antimicrobial agents, it is possible for clinicians to
      treat this infection effectively and reduce the mortality rate.

PMID- 19385504
TI  - Endocannabinoid system and cardio-metabolic risk.
AB  - Recent research in bio-medical science has shown an integral role of
      endocannabinoid system (ECS) in determining cardio-metabolic risk of human body.
      The mechanism is mediated through binding of endocannabinoids at the CB1
      receptors. The stimulation of CB1 receptor in the brain is believed to control
      and mediate the effects on appetite. In normal physiology, CB1 receptors
      activation is responsible for energy homeostasis, govern emotions and behaviors
      such as anxiety, fear, appetite, food and water intake. CB1 receptors also found
      in peripheral tissues like liver, pancreas, skeletal muscles and adipose tissues,
      which play an important role in lipid and glucose metabolism. Over-activation of
      ECS is associated with various metabolic diseases such as dyslipidemia, insulin
      resistance, lipogenesis, excessive weight gain and increasing intra-abdominal
      obesity. All these events lead to increased cardiovascular risk. Use of selective
      CB1 receptor blocker such as rimonabant has shown to reduced waist circumference,
      better glycemic control, lower triglyceride levels, raise HDL cholesterol and
      over all reduction in total body fat. This drug has been recommended for patients
      with metabolic syndrome.

PMID- 19385505
TI  - Foot kinematics in gait of children with cerebral palsy (CP).
AB  - Cerebral palsy (CP) is a developmental disorder of motor, psychological and
      emotional functions. Its most typical symptom is a walking disorder. The aim of
      this study was to analyze children's walking abilities based on basic kinematic
      parameters. In this research, the analysis of a three-dimensional kinematical
      movement is used to record the right and left parts of the child's body. The
      walking skills of two CP children are described. For locomotion analysis, the
      angular displacements in the right and left knees and ankles and foot distortion
      in both support and swing phases of the walk were chosen. The kinematic
      parameters can be helpful in the diagnosis and allow physiotherapists to suggest
      what exercise program should be develop in order to improve the habit of walking.

PMID- 19385506
TI  - Elastic silicone matrices as a tool for load relief in overdenture implants.
AB  - The objective of this study was to analyze how the elasticity of matrices
      attaching to an overdenture affects implants and how the location of implants
      affects their loading. The attachments proposed made from elastic matrix increase
      the denture stability and simultaneously preserve the mechanisms of occlusion
      load transfer in compliance with principles usually applied in the denture used
      in the case of edentulous maxilla or mandible. It was revealed that denture
      dislodgement caused by occlusion forces did not result in the force being greater
      than the attachment retention force determined empirically. Our analysis also
      demonstrates that in the case where the implants are inserted in such a way that
      they are shifted too much to the back area of the tooth arc, an increase in the
      implant bending occurs, with the supporting capacities of alveolar processes not
      being fully utilized. This fact suggests the necessity to increase the
      susceptibility of attachments in a posterior location.

PMID- 19385507
TI  - Mechanical properties of temporomandibular joint disc on the basis of porcine
      preparation investigations.
AB  - The paper presents the results of a study on mechanical properties of porcine
      temporomandibular joint discs. Taking into account anatomical properties, three
      typical spots were selected for the investigation: the posterior, anterior and
      central parts of the disc. The main focus was on the influence of samples'
      preparation on the changes in mechanical properties. Complete undamaged discs,
      cylindrically cut disc samples of 5 mm in diameter as well as discs of locally
      broken continuity in the upper layer around the measuring zone were prepared.
      Periodic compression was applied during testing, by varying the force in a
      sawtooth control signal. The rate of increasing the force applied equalled 1 N/s
      with a maximum value of 3 N. Based on the stress and strain characteristics
      obtained, the object's rigidity, Young's modulus of the samples, and effective
      Young's modulus of joint discs were calculated. Results showed that the stress
      and strain characteristics of the discs' substance depend on sample preparation,
      measurement location and load history within a given number of cycles. Only the
      fifth load cycle may be considered as stabilized. The most rigid proved to be the
      posterior part of the disc, as the rigidity of the samples, of an incised disc
      and of a complete disc in the fifth loading cycle amounted to 117.9 N/mm, 88.8
      N/mm and 87.1 N/mm, respectively. A central part of the disc exhibited the lowest
      rigidity, whose values for the samples, for an incised disc and for a complete
      disc reached 87.9 N/mm, 70.6 N/mm, and 38.7 N/mm, respectively. Excision of the
      samples resulted in their dehydration, which led to increased rigidity, as
      reflected by Young's modulus values. In the posterior part of the disc, the
      modulus value was 12.56 MPa, while in the anterior part and in the center, these
      values reached 7.25 MPa and 6.99 MPa, respectively. Excised discs also exhibited
      dehydration effects during examination. While loading complete discs, the lowest
      effective values of Young's modulus were obtained, despite the influence of the
      tissues adjacent to the loaded zone, counteracting deformation. The values were
      4.44 MPa, 1.97 MPa and 2.99 MPa for the posterior, central and anterior parts,
      respectively. Present data allow the conclusion that the error introduced due to
      breaking the tissue continuity is greater than the error resulting from ignoring
      substance continuity when applying local loads to an undamaged disc. Therefore,
      it seems more sensible to adopt the effective Young's modulus values in numerical
      analyses rather than to apply the results obtained for the samples cut out of
      discs.

PMID- 19385508
TI  - Stress distribution around a TKR implant: are lab results consistent with
      observational studies?
AB  - Malalignment of Total Knee Replacement prosthesis has been reported to limit the
      implant survival time. We hypothesized that this may be secondary to excessive
      stress occurring at the bone-implant interface, resulting from abnormal load
      transfer across the knee joint. In this study, we conducted Finite Element
      Analysis of a geometrical model of the knee joint after Total Knee Replacement
      with different axial alignments. The calculated stresses and displacements were
      significantly higher with varus knee malalignment than with the valgus one. The
      stresses are not high enough to pose a serious risk of a crack or a fracture but
      might be responsible for chronic pain reported by some patients. In cases where
      optimal implant positioning is not possible, slight valgus malalignment might
      produce better results than varus.

PMID- 19385509
TI  - Dynamic testing of bone grafts.
AB  - The influence of cycling loading force on the substrate made of frozen bone
      grafts was investigated. Three layers of bone grafts were compacted in a
      spherical model of hip joint acetabulum and then subjected to a sinusoidal
      loading force. For each layer a series of N = 30 loading cycles were performed.
      The least impacted grafts were located in the upper part of the acetabulum, close
      to its opening, whereas the bed is the most compacted part. Compacting is a non
      linear process which quickly loses its dynamics during subsequent cycles. Most of
      the compacting was observed during the first cycles and the deformation of bone
      grafts has clearly plastic character. Bone grafts initially compacted by
      orthopedist undergo further compacting when exposed to a cyclic load.

PMID- 19385510
TI  - Influence of developmental hip dislocation on femoral head sphericity:
      experimental study in dogs.
AB  - The aim of this study was to assess the growth and the changes in the shape of a
      femoral head in dog puppies with dislocated and unstable hip joints. Ten 5-week
      old, mountain shepherd puppies were divided into two subgroups. In five animals,
      the femoral head was dislocated, and in the other five dogs, femoral head was
      reduced after the dislocation procedure, making the joint congruent but unstable.
      After 4 weeks the animals were euthanised. The optical method of contour
      measurement of the femoral head sphericity was used. The shape of the dislocated
      femoral head differed from the normal one. The medial part was extended into
      beard-like form. The overgrowth of the femoral heads was significant and from 38%
      to 61% larger compared with the normal contralateral head. The unstable head of
      the second group did not differ in the shape nor in its size from the
      contralateral normal one. The large adaptive and deforming changes of shape in
      the dislocated femoral heads in our study show the pronounced malformation of the
      joint. The shape of beard-like deformity may be explained by the enlargement of
      contact surface between the medial part of the head and illiac bone. The
      restricting modelling role of the acetabulum, the minor vascular impairment
      during the surgery and the short time of follow-up were possible factors
      contributing to the minimal changes of the affected femoral head in the unstable
      but congruent hip joint.

PMID- 19385511
TI  - Studies on constitutive equation that models bone tissue.
AB  - A method for identifying viscoelastic constitutive equations for bone is
      developed. In the method, anisotropy, non-homogeneity and bone remodelling are
      taken into consideration. The equations correspond to monotropic rheological
      model of bone. In order to calculate the material parameters of elasticity and
      viscosity, a new algorithm is developed, in which the results of creep
      compression and shear tests are used. The way of determining the material
      constants of elasticity and viscoelasticity for bone in the areas that are
      crucial in strain and stress analysis is shown a well. The strength experiments
      (tests) and creep tests were performed on bone samples extracted from the femur
      of calf. The method of bone modelling in terms of rheology is the following: bone
      samples are properly prepared from biological material. For given bone samples,
      which have more or less the same density, three independent short-term creep
      tests are carried out. The results of the creep tests permit us to determine five
      elastic constants and viscoelastic constants of a monotropic material [1]. In
      order to describe rheological processes in terms of structural models, fractional
      exponential functions and normal exponential functions are used. The constitutive
      equations are formulated in the compliance form. The computer program that
      executes the algorithm of elastic and viscoelastic constant determination is
      used.

PMID- 19385512
TI  - Experimental determination of cervical spine mechanical properties.
AB  - The results of research into human cervical spine mechanical parameters necessary
      for process modelling are presented. Our tests were divided into identification
      of tissues mechanical features and determination of data useful for validating
      human cervical spine models. Mechanical properties of the whole cervical spine as
      well as the stiffness of ligaments and discs were identified on the basis of
      tests on cadaveric spinal specimens. Thanks to our cooperation with medical
      practitioners, physiological cross-section areas of neck muscles were analysed
      using MRI. Functional computed tomography was used to determine kinematics of
      cervical vertebrae during head movement in sagittal and frontal planes.

PMID- 19385513
TI  - Improving surgical precision--application of navigation system in orthopedic
      surgery.
AB  - Navigation systems track objects with precision expressed as root mean square
      equalling even up to 0.15 mm. Application of navigation system combined with
      imaging technique makes surgical operations less invasive, which results in the
      reduced risk of infection, smaller scar and a shorter time of rehabilitation.
      Imaging techniques allow surgeon to create individual virtual models for virtual
      surgery planning. Navigation system tracks the positions of surgical tools in
      relation to the patient's coordinate systems. Medical imaging enables low
      invasive surgery, whereas the position of surgical instruments is monitored on
      screen. The paper presents a newly developed computer-aided surgical system
      consisting of ultrasonographic probe and tracking system to measure bone
      geometry, design surgical scenario virtually and follow it intraoperatively. The
      system assists surgeon to correct bone deformities. The paper presents the
      results of several accuracy tests, which demonstrate good repeatability and
      accuracy.

PMID- 19385514
TI  - Avoiding complications in the treatment of humeral fractures.
AB  - Three of the most common complications that may occur after the treatment of
      humeral fractures are nonunion, loss of fixation, and nerve injury. Nonunion may
      occur in up to 15% of patients who have been treated surgically. Loss of fixation
      often is caused by poor quality bone in the osteopenic humeral head. Nerve injury
      can occur as a result of trauma or from treatment.

PMID- 19385515
TI  - Prevention of complications after treatment of proximal femoral fractures.
AB  - Two factors are primarily responsible for complications after treatment of
      proximal femoral fractures. First, the strong deforming forces across the hip
      joint and proximal femur can make fracture reduction difficult. Second, the
      placement of the implant affects fracture healing and outcome more dramatically
      than in other areas of the body. In subtrochanteric fractures, the use of
      appropriate reduction and stabilization techniques can prevent varus malreduction
      and subsequent failure of the fixation device. In intertrochanteric fractures,
      lag screw cutout can be prevented by correct implant positioning. In femoral neck
      fractures, nonunion can be avoided by careful attention to reduction and hardware
      positioning.

PMID- 19385516
TI  - Prevention of complications after treatment of femoral shaft and distal femoral
      fractures.
AB  - The need for surgical treatment of femoral shaft and distal femoral fractures is
      undisputed. The treatment options are varied, and often the choice is based on
      the surgeon's preference rather than orthopaedic science. The decision should be
      determined by the predicted functional outcome rather than by the type of implant
      to be used. The entry point for intramedullary femoral nailing is of no
      consequence, if the nailing is performed correctly and the patient has a good
      functional outcome. The primary goal of treatment for a supracondylar femoral
      fracture is to restore limb alignment while preventing angular deformity. Proper
      technique, not the choice of a nail or plate, is key to recovery.

PMID- 19385517
TI  - Avoiding complications in the care of fractures of the tibia.
AB  - Tibial fractures are the most common long-bone fractures. Orthopaedic surgeons,
      regardless of their subspecialty, often must treat these injuries, which range
      from low-energy, minimally displaced fractures to limb-threatening injuries with
      neurologic and vascular damage and significant damage to the soft-tissue
      envelope. Tibial shaft fractures are often prone to complications, such as apex
      anterior and valgus malalignments after nailing of the fractures in the proximal
      one third of the tibia, infection after open fractures, and aseptic nonunions.
      Understanding the common complications will aid in preventing them and will allow
      recognition and provide treatment strategies when such problems occur.

PMID- 19385518
TI  - Avoiding complications in the treatment of pronation-external rotation ankle
      fractures, syndesmotic injuries, and talar neck fractures.
AB  - Fractures of the foot and ankle are common injuries that often are successfully
      treated nonsurgically; however, some injuries require surgical intervention. To
      restore anatomy and avoid the need for additional surgery, surgeons must pay
      attention to detail and understand common, avoidable complications. The surgeon
      should have an understanding of the pathologic characteristics of three common
      injuries of the foot and ankle as well as the potential complications and their
      prevention.

PMID- 19385519
TI  - The management of complications associated with tibial fractures.
AB  - Tibial fractures are common and frequently require surgical stabilization. These
      two factors mean that complications when treating this difficult injury are to be
      expected. The objectives in the treatment of open tibial shaft fractures are to
      prevent sepsis, achieve union, and restore function of the limb. However, these
      goals are often compromised by infection, compartment syndromes, and bone loss
      associated with many tibial shaft fractures. Recent studies provide a better
      understanding of the factors involved in the initial care of patients with open
      tibial fractures and have challenged prior dogmas and practices. An example is
      studies that define the relationship between the time to debridement of open
      fractures and subsequent infection. The diagnosis of compartment syndromes
      continues to be challenging. Careful review of clinical criteria will assist
      physicians in the early recognition and the management of compartment syndromes.
      Despite uncomplicated initial care, infections will occur. However, improved
      knowledge in the basic science of infections, specifically infections about
      orthopaedic implants, has led to the development of protocols for treatment and
      obtaining union. Bone loss, a result of either infection or trauma, is one of the
      most difficult complications to manage. Research regarding bone morphogenesis and
      the synthesis of multiple compounds has created new options for treating tibial
      fractures with bone loss.

PMID- 19385520
TI  - Fractures of the femoral neck.
AB  - Fractures of the femoral neck are increasing at an exponential rate as a result
      of the longevity of the general population. The Garden and Pauwels
      classifications both are routinely used to describe displacement and stability of
      femoral neck fractures. Osteonecrosis and nonunion remain problematic because of
      the compromised blood supply to the femoral head in displaced fractures.
      Nondisplaced fractures and displaced fractures in patients physiologically
      younger than 65 years are treated with closed or open reduction and internal
      fixation. Anatomic reduction is the single most important step in the treatment
      and fixation of these difficult fractures. Because of the higher complication
      rate in patients physiologically older than 65 years, a prosthetic replacement
      may be considered for the treatment of displaced fractures. In patients who are
      low-level community ambulators or nursing home ambulators with comorbidities and
      who are not expected to live more than 5 years after injury, a hemiprosthesis is
      indicated. In active, elderly patients physiologically older than 65 years who
      are expected to live longer than 5 years after injury, a total hip replacement is
      the treatment of choice. Total hip replacement relieves pain and allows faster
      rehabilitation than other forms of treatment in this age group. Patients with
      preexisting hip disease also are treated with total hip replacement. An algorithm
      that considers physiologic age and activity level of the patient is helpful when
      deciding whether to fix or replace the hip in a patient with a displaced femoral
      neck fracture. It is also useful in deciding what type of prosthesis to use. The
      treatment of femoral neck fractures remains complex and difficult. Because of the
      enormous burden of this injury, orthopaedists must improve results in the care of
      femoral neck fractures.

PMID- 19385521
TI  - Treatment of femoral neck fractures in young adults.
AB  - Femoral neck fractures in physiologically young adults, which often result from
      high-energy trauma, are less common than intracapsular femoral neck fractures in
      elderly patients. They are associated with higher incidences of femoral head
      osteonecrosis and nonunion. Understanding the multiple factors that play a
      significant role in preventing these complications will contribute to a good
      outcome. Although achieving an anatomic reduction and stable internal fixation
      are imperative, other treatment variables, such as time to surgery, the role of
      capsulotomy, and the method of fixation remain debatable. Open reduction and
      internal fixation through a Watson-Jones exposure is the recommended approach.
      Definitive fixation can be accomplished with three cannulated or noncannulated
      cancellous screws. Capsulotomy in femoral neck fractures remains a controversial
      issue, and the practice varies by institution, region, and country. The timing of
      the open reduction and internal fixation is controversial. Until conclusive data
      are available through prospective, controlled studies, performing a capsulotomy
      followed by open reduction and internal fixation on an urgent basis is
      recommended. The goals of treating femoral neck fractures should include early
      diagnosis, early surgery, anatomic reduction, capsular decompression, and stable
      internal fixation.

PMID- 19385522
TI  - Salvage of failed treatment of femoral neck fractures.
AB  - The number of patients treated for femoral neck fractures continues to increase.
      Although most fractures will heal, reported rates of nonunion and osteonecrosis
      are cause for concern; therefore, implementation of effective salvage strategies
      is important. The choice of salvage strategy generally is guided by patient age,
      remaining bone quality, the status of the articular surface of the hip joint, and
      the viability of the femoral head. Nonunions in patients younger than 60 years
      are typically treated with valgus-producing osteotomies, which convert shear
      forces to compressive forces and have demonstrated relatively high union rates.
      The role of various vascularized and nonvascularized bone grafts remains
      undefined. Nonunions in patients older than 60 years are typically salvaged with
      some form of hip arthroplasty. Both hemiarthroplasty and total hip arthroplasty
      can be effective. Surgical challenges include osteopenic bone; bony defects from
      hardware; and contracted, scarred, and shortened limbs. Careful attention to
      detail during surgery is necessary to avoid complications and provide durable
      reconstructions in this setting.

PMID- 19385523
TI  - Improving outcomes after pertrochanteric hip fractures.
AB  - Complex pertrochanteric fractures, such as those with reverse obliquity and
      subtrochanteric extension, represent a subset of hip fractures that sometimes is
      difficult to treat. Critical assessment of the available literature and a review
      of treatment indications, implant recommendations, and technical pitfalls will
      provide insight to physicians to enable better care of patients with these
      complex injuries.

PMID- 19385524
TI  - Periprosthetic femoral fractures.
AB  - Periprosthetic fractures of the femur are increasing both in the absolute number
      of fractures per year and in frequency (proportion of fractures among patients
      with hip arthroplasty). As a result, orthopaedic surgeons will face these
      challenging injuries more often. The optimal treatment must be individualized,
      taking into consideration the fracture location relative to the arthroplasty
      component, the implant stability, the underlying quality of the bone, and the
      medical and functional status of the patient. Based on these factors, successful
      treatment usually involves some combination of open reduction, internal fixation,
      and revision arthroplasty with or without adjuvant bone grafting.

PMID- 19385525
TI  - Orthopaedic war injuries: recent developments in treatment and research.
AB  - Musculoskeletal injury is the most common type of injury among survivors of
      combat trauma, and combat-related trauma is challenging for an orthopaedic
      surgeon to treat. Methods of treatment are evolving, but significant gaps remain
      as knowledge of civilian trauma is extrapolated to combat trauma.

PMID- 19385526
TI  - Gunshot wounds: epidemiology, wound ballistics, and soft-tissue treatment.
AB  - The extremities are the most common anatomic location for gunshot wounds. Because
      of the prevalence of gunshot injuries, it is important that orthopaedic surgeons
      are knowledgeable about caring for them. The most common injuries seen with
      gunshot wounds are those of the soft tissues. Nonsurgical management of patients
      who have gunshot wounds with minimal soft-tissue disruption has been successfully
      accomplished in emergency departments for several years; this includes extremity
      wounds without nerve, intra-articular, or vascular injury. Stable, nonarticular
      fractures of an extremity have also been successfully treated with either minimal
      surgical or nonsurgical methods in the emergency department. Indications for
      surgical treatment include unstable fractures, intra-articular injuries, a
      significant soft-tissue injury (especially with skin loss), vascular injury,
      and/or a large or expanding hematoma.

PMID- 19385527
TI  - Basics of primary total hip arthroplasty: preoperative and postoperative
      decisions.
AB  - Preoperative planning, choice of implant-bearing surface materials to reduce
      wear, factors to minimize the incidence of postoperative dislocation, and the
      critical postoperative care issues to facilitate a rapid recovery are important
      considerations in patients undergoing total hip arthroplasty.

PMID- 19385528
TI  - Primary total hip arthroplasty: intraoperative decisions and surgical techniques.
AB  - Intraoperative decisions and surgical techniques are important factors in the
      success of a total hip arthroplasty. Each of the available surgical exposures has
      advantages and disadvantages. Reproducing accurate leg length and precisely
      implanting the acetabular and femoral components also are critical.

PMID- 19385529
TI  - Perioperative blood management in total hip arthroplasty.
AB  - Blood management during total hip arthroplasty is a critical component of
      successful patient care, and an overall strategy is necessary. Multiple options
      for blood management are available, including the use of predeposited autologous
      blood, perioperative blood salvage, hemodilution techniques, erythropoietic
      agents, hemostatic agents, and allogeneic blood. Rather than relying on automatic
      so-called transfusion triggers, the surgeon should identify patient-specific risk
      factors such as the anticipated difficulty of the procedure, preoperative
      hemoglobin level, comorbidities, and a plan for blood management.

PMID- 19385530
TI  - Severe femoral bone loss in infected total hip arthroplasty: surgical management.
AB  - The management of severe bone loss in a patient with a chronically infected total
      hip arthroplasty is a complex surgical challenge. The surgical alternatives are
      numerous and include the use of allografts, both structural and morcellized;
      cemented and cementless femoral components; and segmental replacement
      megaprostheses.

PMID- 19385531
TI  - Vancouver type B3 periprosthetic fractures: evaluation and treatment.
AB  - Periprosthetic fracture with preexisting severe loss of bone stock is a
      challenging condition to treat. Available surgical options can be divided into
      three categories: complex reconstruction of the deficient proximal femur with
      secure distal fixation; segmental substitution of the proximal femur with a
      megaprosthesis or allograft/stem composite; and distally fixed replacement with a
      modular stem, which acts as a scaffold around which the remaining deficient
      proximal bone can be assembled, to unite and possibly reconstitute.

PMID- 19385532
TI  - Revision total hip arthroplasty for instability: surgical techniques and
      principles.
AB  - Instability is one of the most common complications after total hip arthroplasty.
      Fortunately, instability usually occurs as a single episode and can successfully
      be treated nonsurgically in many instances. However, recurrent instability may
      require surgical treatment. Although many studies related to instability exist,
      the etiology and the optimal management of recurrent instability are not well
      known and continue to be investigated. It is important to understand the
      principles of management and surgical techniques for the treatment of recurrent
      instability, including the use of constrained liners.

PMID- 19385533
TI  - The peritrochanteric space of the hip.
AB  - The field of hip arthroscopy continues to grow as surgeons become more familiar
      with disorders of the intra-articular and extra-articular compartments of the
      hip. Recent studies have described the endoscopic treatment of injuries to the
      lateral peritrochanteric compartment of the hip, including recalcitrant
      trochanteric bursitis, external coxa saltans, and tears of the gluteus medius and
      minimus tendons.

PMID- 19385534
TI  - Conventional radiographs to assess femoroacetabular impingement.
AB  - Femoroacetabular impingement (FAI) is a pathologic condition of the hip joint in
      young adults that, if untreated, leads to end-stage osteoarthritis. It is
      characterized by early pathologic contact between primary osseous prominences of
      the acetabular rim (so-called pincer FAI) and/or the femoral head-neck junction
      (cam FAI). Conventional radiographs are often considered normal because classic
      radiographic signs of osteoarthritis are not present initially. The physician
      should be aware of the radiographic features for both types of impingement to
      recognize subtle pathologies.

PMID- 19385535
TI  - The young adult with hip impingement: deciding on the optimal intervention.
AB  - Femoroacetabular impingement is a recognized cause of hip pain and osteoarthritis
      in young adults. The clinical presentation of this pathology is quite varied in
      terms of the underlying deformity, patient age, and the degree of cartilage
      damage. Open hip surgery with surgical dislocation is the gold standard for
      treating femoral deformities and the damaged acetabular labral complex; however,
      less invasive techniques such as hip arthroscopy and arthroscopy combined with
      limited anterior hip arthrotomy may provide comparable outcomes with less
      surgical morbidity. Unresolved issues include the indications for acetabular rim
      trimming with labral refixation in the presence of acetabular retroversion and/or
      delaminated acetabular cartilage. Other issues involve the use of arthroplasty in
      older patients and/or in those with significant cartilage damage.

PMID- 19385536
TI  - Femoroacetabular impingement: treatment of the acetabular side.
AB  - Over the past decade, femoroacetabular impingement (FAI) has become an
      increasingly recognized pathomechanism that may explain why some hips that were
      previously considered to have normal morphology fail early in life. Subtle
      morphologic alterations in the acetabulum or femur, as well as the degree of
      hypermobility or impact on the hip, affect the potential for joint damage. The
      most frequent location of FAI is the anterosuperior acetabular rim, and the most
      critical motion is internal rotation of the hip in flexion. Because medication,
      activity restrictions, and physical therapy are rarely successful in treating
      symptoms caused by FAI, surgery has become a mainstay of treatment. Acetabular
      causes of FAI, called pincer FAI, can be treated by improving hip clearance.
      Independent of whether local or global overcoverage is present, rim reduction
      should be combined with labral preservation whenever possible.

PMID- 19385537
TI  - Arthroscopic management of femoroacetabular impingement.
AB  - Femoroacetabular impingement is a well-recognized cause of intra-articular
      pathology and secondary osteoarthritis among young adults. It has been proposed
      that femoroacetabular impingement that does not require periacetabular osteotomy
      sometimes can be managed by arthroscopic methods. Clinically relevant impingement
      is suspected based on the patient history, examination findings, and radiographic
      features. Pathologic impingement is then substantiated based on the arthroscopic
      parameters of characteristic intra-articular pathology. Early experience has
      shown that hip arthroscopy can achieve results that compare favorably to open
      methods in patients with femoroacetabular impingement.

PMID- 19385538
TI  - Extended retinacular soft-tissue flap for intra-articular hip surgery: surgical
      technique, indications, and results of application.
AB  - Osteotomies of the proximal femur for hip joint conditions are normally done at
      the intertrochanteric or subtrochanteric level. Intra-articular osteotomies would
      be more direct and therefore allow a more powerful correction with no or very
      little undesired side correction. However, concerns about the risk of vascular
      damage and osteonecrosis of the femoral head have so far basically excluded this
      technique from practical use. Based on detailed knowledge of the vascular anatomy
      of the proximal femur, an approach to safely dislocate the femoral head has been
      described and successfully performed. Experience as well as further studies of
      femoral head perfusion allowed a substantial extension of this approach, with
      subperiosteal exposure of the circumference of the femoral neck with constant
      intraoperative control of the blood supply to the head. Using the extended
      retinacular soft-tissue flap, four surgical techniques (relative neck
      lengthening, subcapital realignment in slipped capital femoral epiphysis, true
      femoral neck osteotomy, and femoral head reduction osteotomy) evolved or became
      safer with respect to perfusion of the femoral head. The extended retinacular
      soft-tissue flap offers the technical and biologic possibility for a new class of
      intra articular procedures. Although meticulous execution of the surgical steps
      is important, the procedures have a high level of safety for femoral head
      perfusion.

PMID- 19385539
TI  - The correlation between minor or unrecognized developmental deformities and the
      development of osteoarthritis of the hip.
AB  - The 20th century brought three major conceptual changes about osteoarthritis of
      the hip. The first was a dramatic change in the understanding of the etiology of
      many cases of osteoarthritis of the hip. The second was the establishment of the
      mechanism by which minor developmental abnormalities lead to arthritis. The third
      was, for the first time, the possibility that the rate of disease development
      could be retarded and even possibly prevented from progressing. To understand
      these conceptual changes, it is essential to define the terms used to describe
      osteoarthritis of the hip.

PMID- 19385540
TI  - Intraoperative issues concerning the patellofemoral mechanism during total knee
      arthroplasty.
AB  - The patellofemoral joint historically has been a significant source of poor
      clinical outcomes in total knee arthroplasty. Patellar maltracking, peeling of
      the patellar tendon insertion, and difficult exposure are conditions that must be
      addressed and corrected during surgery. A surgeon with a repertoire of techniques
      to handle patellofemoral problems intraoperatively can prevent or correct these
      problems with confidence.

PMID- 19385541
TI  - Resistant organisms in infected total knee arthroplasty: occurrence, prevention,
      and treatment regimens.
AB  - Infection of a primary joint arthroplasty can be a life-changing event for a
      patient. When the infecting organism demonstrates antibiotic resistance,
      treatment can be prolonged, and the chances for a successful outcome may be
      decreased. Antibiotic resistance has been an evolutionary process since the
      introduction of pharmacologic treatment and until recently has been more
      problematic with nosocomial types of infections. Methicillin-resistant
      Staphylococcus aureus skin infections within the community among school or sports
      teams has been a recent cause for concern. Hospitals have implemented screening
      and/or isolation procedures to reduce the risk of spreading these resistant
      organisms and identify patients colonized with resistant organisms. These
      measures have been successful in patients undergoing total joint arthroplasty. It
      is important for the orthopaedic surgeon to be knowledgeable about the emergence
      of resistant bacteria, preoperative and intraoperative screening guidelines, and
      postoperative considerations to prevent resistant organism infections in total
      joint arthroplasty patients.

PMID- 19385542
TI  - Adolescent shoulder injuries: consensus and controversies.
AB  - Adolescent participation in sports is at an all-time high. Younger patients also
      are competing with a greater intensity level, frequently playing organized sports
      throughout the year. Players are putting greater demands on their shoulders,
      making them more prone to injuries. Because these players are in the process of
      skeletal development, certain considerations are needed for this patient
      population. There is controversy regarding the appropriate treatment of these
      adolescent athletes- including debate on injury prevention; nonsurgical treatment
      versus surgical treatment; overuse injuries; and return to play after shoulder
      fractures, dislocations, and instability. It is valuable to review evidence in
      the current literature regarding recommendations for the treatment of shoulder
      injuries in adolescent athletes.

PMID- 19385543
TI  - The treatment of primary anterior shoulder dislocations.
AB  - The treatment of primary anterior shoulder dislocations is complex and
      challenging. The goal of treatment is to achieve a stable, pain-free shoulder
      with a full range of motion. The currently available evidence on the outcomes of
      nonsurgical treatment and immediate surgical stabilization conflicts; decision
      making must also take into account patient-specific variables, including age,
      occupation, functional demands, sports participation, physical characteristics,
      and compliance. Although recurrence rates after anterior shoulder dislocation are
      difficult to pinpoint, abundant data indicate that the shoulder is more
      vulnerable to instability after a first traumatic dislocation. Relatively young
      patient age at the time of injury is the most consistent and significant
      prognostic factor for recurrent instability. Male gender is independently
      predictive of recurrent instability. Most recent studies have not identified
      sports participation or a type of sports activity as correlated with the risk of
      recurrent instability. Nonsurgical treatment typically involves closed reduction,
      a period of immobilization, and physical therapy for strengthening the rotator
      cuff and scapular stabilizers. The evidence for this treatment strategy is
      largely anecdotal, and the literature on its efficacy is inconclusive. Several
      recent studies suggested that immobilization of the shoulder in external rotation
      after a primary traumatic anterior shoulder dislocation may decrease the risk of
      recurrent instability more than conventional sling immobilization. The limited
      evidence available from randomized, controlled trials supports early surgical
      stabilization of a first traumatic anterior dislocation in high-risk young adults
      who engage in demanding physical activities. Although different outcome tools
      were used, the reported recurrence rates and functional outcomes consistently and
      significantly favored surgical treatment over nonsurgical treatment in this
      population of young, active patients. Early or prophylactic stabilization is not
      advisable unless the patient has a high risk of recurrence.

PMID- 19385544
TI  - Arthroscopic bankart repair for unidirectional shoulder instability.
AB  - A successful arthroscopic Bankart repair for unidirectional shoulder instability
      requires careful patient selection and, to the extent possible, the restoration
      of normal anatomy. The patient's goals and anticipated demands are important
      considerations. A patient who participates in an overhead sport requires not only
      a stable shoulder but also a full range of shoulder motion. An athlete who
      engages in a contact or collision sport, however, may tolerate a mild loss of
      motion provided the shoulder is stable. Compared with an open procedure, an
      arthroscopic repair provides the opportunity to retain the most normal
      postoperative range of motion and function. Other considerations include patient
      age, which often relates to overall tissue laxity, and the number of previous
      instability episodes, which correlates with the severity of pathology (in
      particular, capsulolabral strain, glenoid chondromalacia, and bony deficiency of
      the glenoid or posterior humeral head). The magnitude of bone loss, particularly
      for the anterior glenoid, can make an arthroscopic repair inadvisable. Accurate
      portal placement, glenoid preparation, anchor insertion, and suture passage are
      key components of the arthroscopic technique, but the most important overall goal
      is the secure restoration of capsulolabral tissue tension. Secondary
      posteroinferior laxity, partial rotator cuff tears, labral disorders, and
      articular cartilage pathology may also require treatment.

PMID- 19385545
TI  - Posterior and multidirectional instability of the shoulder.
AB  - The shoulder is an inherently unstable joint that is subject to different
      patterns of instability. Determining the direction of subluxation that is causing
      the patient's symptoms can be difficult. Although posterior and multidirectional
      instability share many characteristics, they have different etiologies and
      treatment requirements. Multidirectional instability was first described in 1980
      by Neer and Foster, but the continuing lack of a consistent definition for the
      condition contributes to difficulty in both diagnosis and treatment. Posterior
      instability has been more precisely defined, but the diagnosis nonetheless can be
      difficult. For most patients with either condition, rehabilitation and bracing
      are the preferred treatment. If nonsurgical treatment is unsuccessful,
      arthroscopic treatment can provide a satisfactory result.

PMID- 19385546
TI  - Glenohumeral bone defects in the treatment of anterior shoulder instability.
AB  - There is a well-recognized association between osseous defects of the glenoid or
      humerus and shoulder dislocation, which often leads to recurrent instability. A
      variety of strategies have been used to treat bone loss, and procedures have
      become more refined as the goals of surgery have evolved. Achieving optimal
      motion and function and minimizing the risk of osteoarthritis have become almost
      as important as stabilizing the joint.

PMID- 19385547
TI  - Graft selection for anterior cruciate ligament reconstruction.
AB  - More than 100,000 anterior cruciate ligament reconstructions are done in the
      United States each year. With improvements in technology and surgical ability,
      the number of variables that must be considered has increased dramatically. The
      choice of autograft or allograft, which is one of the most important variables,
      has largely become a decision to be made by the surgeon and the patient. It is
      critical to understand the advantages and disadvantages of each type of graft to
      make informed and intelligent decisions.

PMID- 19385548
TI  - Complications of anterior cruciate ligament reconstruction.
AB  - Anterior cruciate ligament reconstruction has become one of the most common
      arthroscopic knee procedures, and it has excellent success rates. Intraoperative
      technical complications are uncommon but can be devastating to knee function.
      Each of the multiple steps in the reconstruction has associated complications.

PMID- 19385549
TI  - Posterior cruciate ligament biomechanics and options for surgical treatment.
AB  - Treatment algorithms for posterior cruciate ligament (PCL) injury have evolved
      over the past two decades as the natural history of these injuries has become
      clearer. Whether they are isolated injuries or occur with other ligament trauma,
      PCL ruptures substantially alter knee kinematics. Because of the effects of PCL
      injury and the less than optimal results after nonsurgical treatment, new
      surgical techniques have been developed. Several surgical techniques currently
      are available for reconstruction of the PCL. Most recent reports suggest that the
      tibial inlay technique is the best choice for restoring posterior tibial
      stability. Tibial inlay PCL reconstructions can be performed through both open
      and arthroscopic approaches. Crucial to the outcome of these procedures is
      detecting all injuries to the secondary restraints, especially the posterolateral
      corner. Failure to recognize and treat these deficits can compromise the results
      of PCL reconstruction, emphasizing the need for a detailed, meticulous physical
      examination when PCL injuries are suspected.

PMID- 19385550
TI  - Evaluation and treatment of the multiligament-injured knee.
AB  - A dislocated knee with tearing of both cruciate ligaments and one or both of the
      collateral ligaments is a severe injury that can result from high-or low-energy
      trauma. Vascular injuries (especially of the popliteal artery), nerve injuries,
      associated fractures, functional instability, and posttraumatic arthrosis all can
      occur with this injury complex. Most of these ligament injuries require surgical
      treatment, although some low-grade medial collateral ligament complex injuries
      can be treated with bracing. The timing of surgical treatment of acute multiple
      ligament injuries depends on the ligaments injured, the vascular status and skin
      condition of the injured extremity, the degree of knee instability, and the
      patient's overall health. It is important to correct all components of
      instability. Delaying reconstruction for 2 to 3 weeks may decrease the incidence
      of arthrofibrosis. Allograft tissue generally is preferred for these complex
      surgical procedures. Currently, there is no conclusive evidence that double
      bundle posterior cruciate ligament reconstruction provides better results than
      single-bundle posterior cruciate ligament reconstruction in the knee with
      injuries to multiple ligaments.

PMID- 19385551
TI  - Evaluation and treatment of acute and chronic injuries to the capsular ligaments
      of the knee.
AB  - Injury to the capsular ligaments of the knee commonly occurs in conjunction with
      cruciate ligament injury. An untreated grade III sprain can lead to recurrent
      meniscal injury, failure of cruciate ligament reconstruction, and arthrosis.
      Careful clinical examination is necessary to identify injuries to discrete
      ligaments and estimate the severity of injuries not discernable on imaging
      studies. A classification system of capsular injury is useful to link the
      diagnosis to a treatment algorithm. Anatomically based surgical procedures for
      acute and chronic sprains of the posteromedial, anterolateral, and posterolateral
      capsular structures have been proven in long-term outcome studies. The goal is to
      restore the anatomy by repair (for an acute sprain) or capsular shift (for a
      chronic sprain), rather than to substitute extra-articular tendon routing.

PMID- 19385552
TI  - Advanced techniques in hip arthroscopy.
AB  - The indications for hip arthroscopy are expanding as the understanding of hip
      disease increases. Improved instrumentation and technical skills also have
      facilitated the ability to treat some hip disorders arthroscopically.
      Femoroacetabular impingement (FAI) is increasingly recognized as a disorder that
      can lead to progressive intra-articular chondral and labral injury. Although FAI
      is usually treated through an open approach, limited-open and all-arthroscopic
      approaches have been described. Various arthroscopic techniques allow treatment
      of labral and acetabular rim pathology as well as peripheral compartment femoral
      head-neck abnormalities. Early outcomes of limited-open and all-arthroscopic
      treatment of FAI are only beginning to be reported but appear to compare
      favorably with those of open dislocation procedures. Although labral tears
      traditionally have been treated with simple debridement, concerns have been
      raised about the consequences of removing the labrum. Modified portal placement
      and hip-specific suture anchors are now being used in an effort to repair some
      labral tears. Snapping hip disorders typically are treated nonsurgically. For
      persistent symptoms, arthroscopic release is successful, compared with open
      release, and allows additional evaluation of the hip joint during surgery.
      Diagnosis and management of traumatic and atraumatic hip instability continue to
      be challenging. Hip arthroscopy has been shown to be effective in the treatment
      of hip instability in some patients. The extra-articular peritrochanteric space
      is receiving increased attention. The arthroscopic anatomy has been well defined,
      but the treatment of greater trochanteric pain syndrome and arthroscopic repair
      of abductor tendon tears are only beginning to be reported. Improved techniques
      and longer-term outcomes studies will further define the optimal role of hip
      arthroscopy.

PMID- 19385553
TI  - Doc, when can he go back in the game?
AB  - In the injured athlete, several criteria must be considered before return to
      play. There are separate considerations for knee injuries, shoulder injuries, and
      general upper and lower extremity injuries, as well as concussion, hypertrophic
      cardiomyopathy, mononucleosis, and spondylolysis. It is important that surgical
      indications, postoperative rehabilitation, and risk for reinjury are reviewed by
      the surgeon before the athlete is allowed to resume activity.

PMID- 19385554
TI  - Typical and atypical shoulder impingement syndrome: diagnosis, treatment, and
      pitfalls.
AB  - The cause of shoulder impingement syndrome usually is considered to be
      compression of the rotator cuff and subacromial bursa against the anterolateral
      aspect of the acromion. The typical symptom is anterolateral shoulder pain that
      worsens at night and with overhead activity. However, the pain may be caused by
      factors other than a hooked acromion. Atypical impingement syndrome most commonly
      results from an os acromiale, a subcoracoid disorder, acromioclavicular joint
      undersurface hypertrophy, a deconditioned rotator cuff, or scapular dyskinesis.
      The correct diagnosis is made through the patient history and physical
      examination, with appropriate diagnostic imaging. Nonsurgical treatment is
      successful for most types of impingement syndrome; if it is not successful, all
      structural causes of mechanical impingement must be corrected.

PMID- 19385555
TI  - Avoidance and treatment of complications in shoulder arthroplasty.
AB  - Total shoulder replacement is well established as a treatment for a painful
      arthritic glenohumeral joint, typically leading to improved shoulder function and
      decreased pain. The frequency of revision surgery is increasing, as it is for hip
      and knee arthroplasty. The most common complications of shoulder arthroplasty can
      be avoided or successfully treated.

PMID- 19385556
TI  - Elbow arthroscopy for posttraumatic arthrosis.
AB  - Posttraumatic stiffness is a common complication after injury to the elbow. The
      loss of motion may significantly limit an individual's ability to perform normal
      activities of daily living. If conservative measures including medication,
      physical therapy, static splinting, and selective injection fail to restore
      functional range of motion, surgical intervention may be warranted. Open
      procedures have been described with reasonable success in restoring motion.
      However, arthroscopic techniques may provide several advantages in these patients
      who have often undergone previous extensive open surgery.

PMID- 19385557
TI  - Coronoid and radial head reconstruction in chronic posttraumatic elbow
      subluxation.
AB  - Chronic elbow subluxation is uncommon but challenging to treat. Although many
      treatment methods have been described, few clinical outcome studies have been
      done because of the infrequency of the condition. Reconstruction has been better
      defined for radial head deficiencies than for the coronoid. Recognizing and
      repairing or reconstructing any associated soft-tissue deficiencies are important
      to a good outcome. For some patients, protecting the reconstruction with a hinged
      external fixator is recommended to allow early range of motion.

PMID- 19385558
TI  - Total elbow arthroplasty for posttraumatic arthrosis.
AB  - Total elbow arthroplasty can be effective in treating acute injuries and
      posttraumatic conditions of the elbow, although typically it is considered a
      salvage procedure. The ideal prosthetic implant appears to be linked and
      semiconstrained, with an anterior flange to resist posterior and rotatory forces.
      The ability to fix the stem without condyle preservation is important in treating
      a posttraumatic condition. The results of total elbow arthroplasty can
      deteriorate over time because of periprosthetic fracture, implant fracture,
      bushing wear, or other mechanical failure. The rate of aseptic loosening is less
      than 10% after 10 years, which is lower than had been anticipated. Elbow
      replacement can be extremely effective for a properly selected patient with
      posttraumatic arthrosis. However, approximately 25% of patients have a
      complication.

PMID- 19385559
TI  - Surgical treatment of bicolumn distal humeral fractures: relevant anatomy and
      classification.
AB  - Intercondylar or bicondylar distal humeral fractures involving both the medial
      and lateral columns are complex periarticular injuries that are challenging to
      treat. Understanding the normal elbow anatomy and classification systems that
      describe injury patterns provides the basis for the successful treatment of these
      complex humeral fractures.

PMID- 19385560
TI  - Surgical exposures for bicolumn distal humeral fractures.
AB  - The surgical management of fractures of the distal humerus is technically
      challenging. The goal is to obtain adequate exposure without causing unnecessary
      morbidity, which can be achieved if the surgeon is familiar with several
      posterior approaches used to expose bicolumn distal humeral fractures. These
      approaches begin with a common medial dissection and branch into progressively
      more extensile exposures.

PMID- 19385561
TI  - Open reduction and internal fixation with 90-90 plating of bicolumn distal
      humeral fractures.
AB  - A bicolumn intra-articular fracture is the most challenging distal humeral
      fracture to treat. Open reduction and internal fixation of these fractures is
      best achieved using either 90-90 medial-lateral or parallel opposing plates.
      Either technique can be used to treat most patients, although in some instances,
      one technique may be preferred over another. The goal of treatment is accurate
      anatomic restoration and stable fixation that will permit early range of motion.

PMID- 19385562
TI  - Parallel plate fixation of bicolumn distal humeral fractures.
AB  - Inadequate fixation of bicolumn distal humeral fractures can result in
      postoperative complications, including nonunion and contracture. Fixation using
      medial-lateral parallel plating provides stable fixation and permits an early and
      intensive program of elbow motion that is associated with a high rate of union.
      Parallel plate fixation locks the two columns of the distal humerus together and
      provides the features and stability of an arch. This construct applies an
      architectural concept and engineering principles to orthopaedic surgery.

PMID- 19385563
TI  - Elbow arthroplasty for the treatment of bicolumn distal humeral fractures.
AB  - Distal humeral fractures are difficult to treat in elderly patients. Recent
      advances in precontoured and locked plates have made open reduction and internal
      fixation easier, but rigid and anatomic reconstruction is required for a
      successful result. In elderly patients with poor bone quality and an
      unreconstructable articular surface, total elbow arthroplasty can be a successful
      alternative to open reduction and internal fixation.

PMID- 19385564
TI  - Postoperative management after open reduction and internal fixation of distal
      humeral fractures.
AB  - Postoperative care is a critically important component in treating patients with
      complex distal humeral fractures. The immediate, intermediate, and late phases of
      the postoperative period present different issues that require specific
      management to maximize the eventual functional outcome for patients with these
      injuries.

PMID- 19385565
TI  - Distal humeral nonunion.
AB  - Nonunion is one of the most common and challenging complications of distal
      humeral fractures. Newer internal fixation principles and techniques have
      improved the ability of orthopaedic surgeons to achieve stable fixation of
      complex distal humeral fractures. However, some fractures will fail to unite,
      leaving the patient with an unstable, dysfunctional, and often painful upper
      extremity that requires additional surgery.

PMID- 19385566
TI  - Arthritis of the thumb basal joint: old and new treatments for a common
      condition.
AB  - Arthritis of the basal joint of the thumb is a condition that is becoming even
      more common as longevity increases and more people have active lifestyles in
      later life. The role of new hyaluronase-based injectable agents is evolving. A
      number of surgical procedures are effective in treating early-stage arthritis;
      the commonly performed trapezium resection and ligament reconstruction procedures
      have been modified by using limited-incision approaches, arthroscopic assistance,
      and bioengineered materials, as well as metacarpal repositioning osteotomy.

PMID- 19385567
TI  - Reconstruction after flexor tendon injury: state of the art.
AB  - The methods used to treat intrasynovial flexor tendon injuries are the result of
      decades of clinical experience coupled with advances in understanding the
      biomechanical, physiologic, and cellular milieu of the repair. Successful
      treatment requires optimizing the factors that can be controlled and ameliorating
      those that cannot be controlled.

PMID- 19385568
TI  - Evaluation and treatment of ankle syndesmosis injuries.
AB  - Athletes sustain ankle syndesmosis injuries far less frequently than they do
      lateral ankle sprains; however, syndesmosis injuries are more challenging to
      detect and treat. Grade II injuries, which are occultly unstable, may be
      overlooked or treated too conservatively (nonsurgically), leading to latent
      diastasis, chronic instability, further injury, arthritic changes, chronic pain,
      osteochondral lesions, and other sequelae. Surgical intervention for chronic
      syndesmosis injuries produces mixed results and creates an uncertain future for
      athletes who desire to return to their sport. Optimal treatment starts with a
      comprehensive evaluation that includes a thorough physical examination as well as
      imaging studies to evaluate for instability (medial clear space widening and
      syndesmosis disruption). All acute unstable syndesmosis injuries (grades II and
      III) should be treated with surgery, which can include repair of the deltoid
      ligament with open reduction and internal fixation of the syndesmosis. Isolated
      deltoid sprains also are often repaired surgically in athletes. This more
      aggressive treatment helps avoid the chronic pain and instability and
      osteochondral abnormalities associated with chronic injury.

PMID- 19385569
TI  - Current management of tarsometatarsal injuries in the athlete.
AB  - The frequency of foot injuries is increasing in certain athletes, particularly
      injuries to the tarsometatarsal joint complex. A high index of suspicion for this
      injury is required to make the diagnosis because the clinical signs often are
      subtle. A comprehensive examination along with bilateral weight-bearing plain
      radiographs of the foot should be obtained in any suspected midfoot injury.
      Further imaging studies and stress radiographs may assist in the diagnosis and
      direct management. Nonsurgical treatment can be considered in a stable sprain
      with less than 2 mm of diastasis between the first and second metatarsal bases on
      a weight-bearing AP foot radiograph. Any tarsometatarsal injury with displacement
      of more than 2 mm or instability requires surgical treatment. Various techniques
      and approaches have been described, depending on the injury pattern, including
      primary arthrodesis and ligament reconstruction. Anatomic reduction is the most
      critical goal in the treatment of these injuries.

PMID- 19385570
TI  - Surgical treatment of the ankle and foot in patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis can be as devastating for the joints of the foot and ankle
      as for other joints of the lower and upper extremities. Early conservative
      treatment often is provided by a primary care provider or rheumatologist. Drug
      and injection therapies are used with footwear modifications, activity
      restrictions, and orthoses. Surgery often is the last treatment modality
      available to the patient; it has the potential to relieve pain and improve
      function.

PMID- 19385571
TI  - Emergency evaluation, imaging, and classification of thoracolumbar injuries.
AB  - Thoracolumbar injuries usually are the result of high-energy trauma and
      frequently are associated with multisystem concomitant injuries. Whenever a
      thoracolumbar injury is suspected, a prompt and thorough evaluation should be
      performed in the emergency department, using the guidelines of the American
      College of Surgeons and including full primary and secondary surveys as well as
      resuscitation. Protection of the spine and spinal cord is of paramount importance
      during the initial evaluation. A careful and complete neurologic examination is
      warranted as part of the secondary survey. Plain radiography, CT, and MRI studies
      are useful in diagnosing and classifying thoracolumbar injuries. At many trauma
      centers, CT has become the standard imaging technology for the initial evaluation
      of the spine. MRI is particularly accurate in detecting injury to the posterior
      ligamentous complex of the thoracolumbar spine. Classification and treatment of
      thoracolumbar injuries are controversial. The comprehensive, reproducible
      classification system of the Spine Trauma Study Group has prognostic significance
      and can guide treatment decisions. The Thoracolumbar Injury Classification and
      Severity scale classifies thoracolumbar injures based on three pivotal
      characteristics: the morphology of the injury, the integrity of the posterior
      ligamentous complex, and the patient's neurologic status. A total severity score
      is used in conjunction with the classification system to determine the treatment.

PMID- 19385572
TI  - Nonsurgical treatment of thoracolumbar spinal fractures.
AB  - The transitional anatomy of the thoracolumbar spine makes it vulnerable to injury
      from high-energy vehicular crashes and falls. The definitive management of
      patients with thoracolumbar spinal fractures is dependent on the presence and
      extent of neurologic injury, the presence and magnitude of acute deformity, and
      an estimate concerning spinal stability. It is well established that neurologic
      deficits generally improve without surgery. Nonsurgical treatment leads to
      decreased pain and improved function. Although there is a dearth of high-quality
      studies comparing surgical with nonsurgical treatment, the natural course of
      thoracolumbar fractures usually is benign, and nonsurgical methods should be the
      standard treatment with few exceptions.

PMID- 19385573
TI  - Surgical treatment of thoracolumbar fractures.
AB  - Surgical management of a thoracolumbar fracture varies according to many factors.
      Fracture morphology, neurologic status, and surgeon preference play major roles
      in deciding on an anterior, a posterior, or a combined approach. The goal is to
      optimize neural decompression while providing stable internal fixation over the
      least number of spinal segments. Short-segment constructs through a single-stage
      approach (anterior or posterior) have become viable options with advances in
      instrumentation and techniques. Unstable burst fractures can be treated with
      anterior-only fixation using a strut graft and a modern thoracolumbar plating
      system or with a posterior-only construct using pedicle screws and possibly
      hooks. A circumferential construct is considered for extremely unstable injuries.

PMID- 19385574
TI  - Sacral fractures.
AB  - Sacral fractures are a treatment challenge for the orthopaedic surgeon. The
      relative rarity of sacral fractures limits physician exposure to these injuries
      and has resulted in questions regarding their optimal treatment. Proper diagnosis
      and classification also are subjects of considerable debate. Studies of sacral
      fractures have been mainly retrospective in nature and have involved
      heterogeneous and small patient populations. The current literature is,
      therefore, limited.

PMID- 19385575
TI  - The pathophysiology and nonsurgical treatment of lumbar spinal stenosis.
AB  - Lumbar spinal stenosis, which affects an ever-increasing number of patients, is
      best defined as a collection of clinical symptoms that includes low back pain,
      bilateral lower extremity pain, paresthesias, and other neurologic deficits that
      occur concomitantly with anatomic narrowing of the neural pathway through the
      spine. The narrowing may be centrally located in the spinal canal or more
      laterally in the lateral recesses or neuroforamina. Lumbar spinal stenosis can
      have a congenital or acquired etiology, and the origin of acquired lumbar
      stenosis is classified as degenerative, posttraumatic, or iatrogenic. In
      degenerative lumbar stenosis, the anatomic changes result from a cascade of
      events that includes intervertebral disk degeneration, facet joint arthrosis, and
      hypertrophy of the ligamentum flavum. The altered biomechanical characteristics
      of the spinal segment perpetuate a cycle of degenerative changes, and the
      resulting stenosis produces radicular pain through a combination of direct
      mechanical compression of nerve roots, restriction of microvascular circulation
      and axoplasmic flow, and inflammatory mediators. The initial treatment of lumbar
      spinal stenosis is nonsurgical. The most effective nonsurgical treatment is a
      comprehensive combination of oral anti-inflammatory drugs, physical therapy and
      conditioning, and epidural steroid injections. A significant number of patients
      improve after nonsurgical treatment, although most studies have found that
      patients treated surgically have better clinical results. Delaying surgical
      treatment until after a trial of nonsurgical treatment does not affect the
      outcome. Surgical intervention should be considered only if a comprehensive
      program of nonsurgical measures fails to improve the patient's quality of life.

PMID- 19385576
TI  - Surgical treatment of lumbar spinal stenosis associated with adult scoliosis.
AB  - Lumbar spinal stenosis associated with adult scoliosis is being increasingly
      recognized and studied. Degenerative changes leading to spinal stenosis can
      precede a spinal deformity resulting in de novo scoliosis. Conversely,
      degenerative changes leading to spinal stenosis can occur in a preexisting
      deformity. Scoliosis has been shown to negatively affect the quality of life in
      adults studied with validated instruments. Surgical intervention can positively
      affect the quality of life in these patients. The optimal surgical procedure
      depends on a careful evaluation of involved segments and patient comorbidities.
      Positive sagittal imbalance is associated with significant morbidity and should
      be corrected when feasible. Data that continue to be collected in this patient
      population will guide future efforts in treating this complicated disease.

PMID- 19385577
TI  - The use of bone morphogenetic protein in lumbar spine surgery.
AB  - Creating a solid lumbar spinal fusion remains a challenge. Despite advances in
      fixation, a pseudarthrosis still may occur. Recently, attention has focused on
      creating a more biologically favorable environment to enhance fusion rate. Bone
      morphogenetic proteins (BMPs) are a group of secreted growth factors that belong
      to the transforming growth factor-beta superfamily. Two recombinant BMP proteins,
      rhBMP-2 and rhBMP-7 (OP-1), have been used successfully in preclinical and
      clinical trials and are commercially available for clinical applications.

PMID- 19385578
TI  - Anterior cervical fusion: the role of anterior plating.
AB  - Treatment of cervical pathology requires a clear understanding of the
      biomechanical benefits and limitations of cervical plates, their indications, and
      their associated complications. The use of anterior cervical plates has evolved
      significantly since their early application in cervical trauma. They have become
      widely used for anterior cervical decompression and fusion for cervical
      spondylosis. Plate design has undergone significant refinement and innovation,
      from the initial unlocked plates requiring bicortical purchase to the latest
      rotationally and translationally semiconstrained dynamic plates. Excellent
      clinical results have been reported for single-level anterior cervical
      decompression and fusion with or without plate fixation; however, the addition of
      an anterior cervical plate clearly leads to earlier fusion and better clinical
      results in longer fusions. Longer fusions should ideally consist of corpectomies
      and strut grafting because the decreased number of fusion surfaces tends to lead
      to higher fusion rates. Although anterior plate fixation leads to higher fusion
      rates in fusions of three or more levels, the associated pseudarthrosis rate is
      still high. The use of dynamic plates, through increased load sharing across the
      graft and decreased stress shielding, may improve fusion rates, particularly in
      long fusions. Nevertheless, adjuvant posterior fixation is recommended for
      fusions of more than three vertebral levels. Anterior plate fixation may be of
      particular benefit in the management of traumatic injuries, in revision settings,
      and in the treatment of smokers. Complications unique to plate fixation include
      hardware breakage and migration as well as ossification of the adjacent disk
      levels.

PMID- 19385579
TI  - Prevention, identification, and treatment of inadequate decompression of the
      cervical spine.
AB  - Inadequate decompression is one of the most common reasons for failed spinal
      surgery. Understanding the common areas where neural impingement occurs in the
      cervical spine, recognizing these changes on imaging studies, and recognizing the
      clinical manifestations help provide an intraoperative template for thorough
      decompression. A thorough preoperative workup assesses sagittal alignment of the
      cervical spine, determines if instability exists, identifies the location of the
      compression, and determines the etiology of the compressive lesion. This
      information guides the surgeon in deciding whether an anterior, a posterior, or a
      combined anterior and posterior approach will provide the most adequate
      decompression. It also will help determine whether arthrodesis is needed to
      provide optimal neurologic recovery. Patients who have had surgery and present
      with persistent neurologic symptoms, or who do not recover as expected, pose a
      unique challenge. The surgeon must determine if persistent compression exists,
      look for evidence of instability, and evaluate for irreversible spinal cord
      changes. Alternatively, other causes of neurologic changes, unrelated to
      neurologic impingement, must be ruled out. The initial step in achieving the goal
      of complete neurologic decompression is a thorough preoperative evaluation for
      static and dynamic causes of compression. The most important concept regarding
      inadequate decompression is to avoid it with careful preoperative planning of the
      index procedure.

PMID- 19385580
TI  - Vertebral artery injury in cervical spine surgery.
AB  - Vertebral artery injuries during cervical spine surgery are rare, with a reported
      incidence of 0.3% to 0.5%. The vertebral artery enters the vertebral foramen most
      commonly at C6 and courses from anterior and lateral to medial and posterior with
      respect to the vertebral body up to C3. The vertebral artery has a more variable
      course in the atlantoaxial region. Careful assessment on preoperative imaging
      will identify common anomalies and help avoid a vertebral artery injury. If a
      vertebral artery injury occurs, rapid action is required to prevent
      exsanguination or catastrophic neurologic injury. Every attempt should be made to
      repair the vertebral artery because the contralateral artery may not provide
      sufficient blood flow in this spondylotic population. If repair is not possible
      and contralateral circulation is deemed adequate, endovascular coiling or primary
      ligation should be performed. Tamponade should be avoided as the definitive
      treatment because of well-known complications.

PMID- 19385581
TI  - Dysphonia, dysphagia, and esophageal injuries after anterior cervical spine
      surgery.
AB  - Anterior cervical spine surgery is commonly used by spine surgeons to treat
      numerous pathologic entities. The most common procedures involve decompression of
      the cervical spine through either diskectomy or corpectomy. Procedures that
      involve anterior dissection of the neck can lead to various complications,
      including dysphonia, dysphagia, and esophageal injuries.

PMID- 19385582
TI  - Problems related to cervical fusion: malalignment and nonunion.
AB  - Two common complications associated with cervical surgery are malalignment,
      particularly after multilevel laminectomies, and nonunion. In both situations,
      prevention and early recognition are critical in clinical management. In
      postlaminectomy kyphosis, the prevailing cause is an alteration in the normal
      spinal biomechanics. The exact incidence is unknown; however, this malalignment
      can cause significant morbidity. Surgical treatment is used once a patient
      becomes symptomatic. Anterior cervical procedures are frequently used to correct
      the deformity. Like postlaminectomy kyphosis, most nonunions can be prevented.
      The reported incidence of pseudarthrosis has ranged from 0% to 50%. With advances
      in instrumentation and attention to surgical detail, the frequency of this
      complication has decreased. Fortunately, not all nonunions are symptomatic or
      require treatment. For symptomatic nonunions, surgical options include anterior,
      posterior, and combined cervical procedures depending on the pathology. As the
      frequency of cervical procedures continues to increase, it is paramount for spine
      surgeons to be aware of these complications and the various methods to treat
      them.

PMID- 19385583
TI  - Adjacent segment disease after cervical spine fusion.
AB  - Anterior cervical diskectomy and fusion is one of the most common cervical spine
      procedures. Although it is usually successful in relieving the symptoms of
      radiculopathy and myelopathy, the subsequent development of clinically
      significant disk disease at levels adjacent to the fusion is a matter of concern.
      Adjacent segment cervical disease occurs in approximately 3% of patients; the
      incidence is expected to increase to more than 25% of patients within the first
      10 years after the index fusion procedure. The disease is well described in the
      literature, and significant basic science and clinical research has been
      conducted. Nonetheless, the cause of the disease is a matter of debate. A
      combination of factors probably contributes to its development, including the
      increased biomechanical stress placed on the disk space adjacent to a fusion and
      the natural history of cervical spondylosis in patients known to have such
      pathology. Clinical and biomechanical data are available to support each of these
      claims. Symptomatic disk disease adjacent to a cervical fusion is a significant
      clinical problem, and, therefore, motion-sparing technology has been developed to
      reduce its incidence. Two cervical disk replacement systems are currently
      approved by the US Food and Drug Administration for the treatment of symptomatic
      cervical spondylosis.

PMID- 19385584
TI  - Cyclooxygenase-2 inhibitors and other nonsteroidal anti-inflammatory drugs in the
      treatment of musculoskeletal conditions.
AB  - Selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are
      widely used to treat a variety of musculoskeletal conditions. The efficacy of
      these medications has been proved, although the risks have not been clearly
      delineated. Nonselective NSAIDs are associated with gastrointestinal, renal, and
      hematologic complications. The risks of using selective NSAIDs may include
      cardiovascular adverse events. The most appropriate agent should be chosen by
      considering the possible complications as well as the patient's risk profile.

PMID- 19385585
TI  - Postoperative pain management techniques in hip and knee arthroplasty.
AB  - Adequate control of postoperative pain following hip and knee arthroplasty can be
      a challenging task fraught with potential complications. Postoperative pain is
      perceived by the patient via a complex network and a multitude of molecular
      messengers in both the peripheral and central nervous systems. This allows the
      physician to modulate pain via an array of medications that act on different
      sites within the body. Using both contemporary and traditional pain modulators,
      the delivery and timing of these medications can affect postoperative pain and,
      ultimately, rehabilitation of the arthroplasty patient. Current techniques for
      controlling pain use both multimodal and preemptive analgesia to improve the
      outcome of the surgery while minimizing the potential adverse effects of the
      medications given.

PMID- 19385586
TI  - Venous thromboembolic disease after total hip and knee arthroplasty.
AB  - A variety of pharmacologic and mechanical means can be used to prevent
      thromboembolic disease following total hip or knee arthroplasty. The existing
      pharmacologic options are parenteral heparin, fondaparinux, oral warfarin, and
      oral acetylsalicylic acid. An oral form of heparin as well as direct thrombin
      inhibitors of factors IIa, IXa, and Xa are being developed in the hope of
      discovering an agent that effectively prevents thrombi formation but carries a
      low risk of bleeding complications. Mechanical prophylaxis devices include foot
      pumps, calf pumps, and calf and thigh pumps for standard pneumatic compression,
      sequential compression, or rapid inflation compression. Although an ideal
      prophylaxis does not exist, a multimodal approach incorporating pharmacologic and
      mechanical prophylaxis has been proved safe and effective. The published
      recommendations of the American College of Chest Physicians (ACCP) for deep
      venous thrombosis prophylaxis of total joint patients are widely used throughout
      the world. These ACCP guidelines have a rigorous foundation in evidence-based
      medicine and meet the requirements of many oversight groups; some recommendations
      also meet the standards of certain state and federal programs. In the view of
      many orthopaedic surgeons, however, these ACCP guidelines have some notable
      disadvantages. The routine use of relatively aggressive pharmacologic prophylaxis
      has led to complication rates higher than those reported in the studies used by
      the ACCP. Equivalent results have been achieved in reducing symptomatic deep
      venous thrombosis, pulmonary embolisms, and deaths with less aggressive, less
      expensive prophylaxis protocols that still meet the requirements of recently
      enacted federal programs that monitor deep venous thrombosis.

PMID- 19385587
TI  - Prevention of symptomatic pulmonary embolism in patients undergoing total hip and
      knee arthroplasty: clinical guideline of the American Academy of Orthopaedic
      Surgeons.
AB  - A work group of the American Academy of Orthopaedic Surgeons, with the assistance
      of the Center for Clinical Evidence Synthesis at Tufts-New England Medical
      Center, has proposed a guideline for the prevention of symptomatic (and fatal)
      pulmonary embolism in patients undergoing total hip and knee arthroplasty. This
      guideline includes recommendations from both a consensus process and an analysis
      of 42 publications since 1996. The end points included symptomatic and fatal
      pulmonary embolism rates, total death rates, and major bleeding complications.
      The guideline recommends preoperative evaluation of all patients for "standard"
      and "high" risks of both pulmonary embolism and major bleeding complications. The
      use of regional anesthesia, mechanical prophylaxis, rapid mobilization, and
      patient education were consensus recommendations. The choice of a specific
      medication postoperatively should be based on an individual risk-benefit analysis
      of pulmonary embolism and major bleeding complications.

PMID- 19385588
TI  - Osteoporosis: management and densitometry for orthopaedic surgeons.
AB  - Osteoporosis is a metabolic condition that is increasing in prevalence as people
      live longer. A fracture is a sentinel event. Despite all the advances in
      technology, a history of low-energy fracture in adulthood is the best predictor
      of future fracture-an even better predictor than low bone mineral density.
      Osteoporosis and the risk of fracture go hand in hand. The orthopaedic surgeon is
      often viewed as an expert in managing and treating bone disorders. Given that the
      orthopaedic surgeon is often the first and only physician to evaluate a patient
      with a fracture, he or she may be in the ideal position to initiate patient
      evaluation and therapy. However, many times the orthopaedic surgeon is concerned
      about the adverse effects of the pharmacologic treatment of osteoporosis to the
      extent that prescribing these drugs is avoided. A treatment approach
      incorporating nonpharmacologic agents is an effective strategy in the prevention
      and treatment of osteoporosis.

PMID- 19385589
TI  - Osteoporosis: management and treatment strategies for orthopaedic surgeons.
AB  - Osteoporosis is a metabolic condition that is gaining increasing attention as
      people live longer. It may frequently be present in patients with and without
      fracture. Nonpharmacologic methods and pharmacologic methods may be used to treat
      osteoporosis and related fractures. The ultimate goal in managing and treating
      osteoporosis is to optimize fracture risk reduction. Commonly used
      nonpharmacologic interventions include calcium and vitamin D supplementation,
      fall prevention, hip protectors, and balance and exercise programs. These
      interventions act in conjunction with pharmacologic methods, if prescribed.

PMID- 19385590
TI  - Diagnosis and treatment of joint-related tumors that mimic sports-related
      injuries.
AB  - Tumors involving the joint or having symptoms in the joint are rare. Both joint
      related tumors and sports-related injuries can affect young, active patients, and
      their symptoms often overlap. Sports medicine specialists rarely encounter
      synovial conditions, so expertise in this area is difficult to establish.
      Orthopaedic oncologists often see only patients with an advanced condition. The
      clinical presentation of a soft-tissue sarcoma may be similar to that of a common
      lesion such as a synovial cyst. Some benign or malignant bone tumors cause
      referred pain to distant joints, possibly leading to a delay in diagnosis or
      inappropriate initial surgery. For example, a hip or proximal femoral bone tumor
      commonly causes isolated knee pain. Conversely, because the symptoms of some
      sports-related conditions or pseudotumors (such as a rectus femoris tear, fascial
      herniation, myositis ossificans, an avulsion injury, an avulsive cortical
      irregularity, femoral diaphyseal periostitis, or pseudotumor deltoideus) are
      similar to symptoms of a sarcoma, overtreatment is possible. A sports medicine
      physician should be familiar with these conditions to facilitate accurate and
      expedient diagnosis with appropriate treatment.

PMID- 19385592
TI  - Spin density distribution of the excited triplet state of bacteriochlorophylls.
      Pulsed ENDOR and DFT studies.
AB  - The photoexcited triplet states of bacteriochlorophyll a and bacteriochlorophyll
      b have been investigated by ENDOR spectroscopy at 34 GHz in frozen solution and
      by DFT calculations. The spin density distributions in the triplet state were
      found to be similar for bacteriochlorophyll a and bacteriochlorophyll b except
      for the presence of spin density on carbon 8(1) in bacteriochlorophyll b. Judging
      from a comparison with ENDOR experiments for the radical cation and anion, the
      triplet state in bacteriochlorophylls cannot be explained as being a simple HOMO-
      >LUMO excitation of Gouterman orbitals. Rather, it must be described as a mixture
      of HOMO-->LUMO and HOMO-1-->LUMO excitations for a satisfactory explanation of
      the observed hyperfine interactions. The observed hyperfine couplings in the
      ENDOR spectra were assigned, and the field dependence of the signals was found to
      be fully compatible with the orientation of the zero-field splitting tensor
      determined from magnetophotoselection studies.

PMID- 19385591
TI  - CD44+ cancer cells express higher levels of the anti-apoptotic protein Bcl-2 in
      breast tumours.
AB  - Breast tumours consist of phenotypically diverse populations of breast cancer
      cells of which only a minority has the ability to form new tumours. The capacity
      for breast tumour development has been shown to be restricted to breast cancer
      stem cells with the CD44+/CD24(-/low) phenotype. These cells can resist apoptosis
      through mechanisms such as the regulation of Bcl-2. Identification of this
      population of cells is important because of its implication in the development of
      new therapeutic strategies. One hundred and forty-six primary operable breast
      cancer patients were investigated in order to identify the population of CD44+
      and Bcl-2+ cells in paraffin-embedded tissues by immunohistochemistry. The
      prevalence of these phenotypes was then correlated with clinicopathological
      features. CD44 and Bcl-2 expression was detected in 86% and 82% of breast
      tumours, respectively. There was no significant correlation between CD44+ tumour
      cell prevalence and tumour characteristics, whereas the prevalence of CD44+ cells
      was associated with higher levels of Bcl-2 expression (P = 0.004). In univariate
      analysis, Bcl-2 expression was correlated with breast tumours of lower grade (P <
      0.001) and fewer lymphatic metastases (P < 0.05). Our findings suggest that the
      prevalence of CD44+ tumour cells as a subpopulation of breast cancer stem cells
      was of no clinicopathological significance, but was correlated with higher Bcl-2
      expression. This population of tumour cells may thus be more resistant to
      apoptosis. Targeting these cells in combination with current treatments may be
      more effective in treating breast cancer patients.

PMID- 19385593
TI  - Rate constants for the gas-phase reactions of NO3 radicals and O3 with C6-C14 1
      alkenes and 2-methyl-1-alkenes at 296 +/- 2 K.
AB  - Rate constants for the gas-phase reactions of NO(3) radicals and O(3) with a
      series of C(6)-C(14) 1-alkenes and 2-methyl-1-alkenes have been measured at 296
      +/- 2 K and atmospheric pressure of air using relative rate methods. For the
      NO(3) radical reactions, the rate constants obtained (in units of 10(-14) cm(3)
      molecule(-1) s(-1)) were: 1-hexene, 2.00 +/- 0.16; 1-octene, 2.35 +/- 0.15; 1
      decene, 2.55 +/- 0.16; 1-dodecene, 2.79 +/- 0.36; 1-tetradecene, 2.87 +/- 0.21; 2
      methyl-1-pentene, 43.8 +/- 2.3; 2-methyl-1-hexene, 52.4 +/- 2.5; 2-methyl-1
      octene, 57.8 +/- 2.6; 2-methyl-1-nonene, 60.8 +/- 2.9; 2-methyl-1-undecene, 60.8
      +/- 3.3; 2-methyl-1-tridecene, 60.3 +/- 3.4; and cycloheptene, 49.4 +/- 2.0. For
      the O(3) reactions, the rate constants obtained (in units of 10(-17) cm(3)
      molecule(-1) s(-1)) were: 1-hexene, 0.898 +/- 0.054; 1-heptene, 1.05 +/- 0.07; 1
      octene, 1.01 +/- 0.04; 1-decene, 1.11 +/- 0.05; 1-dodecene, 1.38 +/- 0.14; 1
      tridecene, 1.92 +/- 0.12; 1-tetradecene, 2.44 +/- 0.24; 2-methyl-1-pentene, 1.26
      +/- 0.13; 2-methyl-1-heptene, 1.35 +/- 0.05; 2-methyl-1-octene, 1.38 +/- 0.06; 2
      methyl-1-decene, 1.48 +/- 0.07; 2-methyl-1-undecene, 1.46 +/- 0.11; and 2-methyl
      1-tridecene, 2.85 +/- 0.42. The rate constants for the NO(3) radical reactions
      significantly increase with increasing carbon number, attaining a plateau at > or
      = C(14) for the 1-alkenes and at C(10)-C(14) for the 2-methyl-1-alkenes. In
      contrast, the rate constants for O(3) reactions increase only slightly with
      increasing carbon number up to approximately C(10) for the 1-alkenes and
      approximately C(12) for the 2-methyl-1-alkenes, with the significant increase in
      the measured rate constants for the > C(10) 1-alkenes and > C(12) 2-methyl-1
      alkenes possibly being due to heterogeneous reactions. Reasons for the observed
      trends in NO(3) radical and O(3) reaction rate constants with alkene carbon
      number are discussed.

PMID- 19385594
TI  - Proton mobilities in phosphonic acid-based proton exchange membranes probed by 1H
      and 2H solid-state NMR spectroscopy.
AB  - Two novel phosphonic acid-based "dry" proton exchange membrane materials that may
      allow for fuel cell operation above 100 degrees C have been prepared and
      characterized via solid-state 1H and 2H MAS NMR spectroscopy. We obtained
      information on both the nature of hydrogen bonding and local proton mobilities
      among phosphonic acid moieties. In particular, 2H MAS NMR line shape analysis
      yielded apparent activation energies of the underlying motional processes. Using
      this approach, we have investigated both a model compound and a novel PEM system.
      It was found that the relation of estimated hydrogen-bond strength and local
      proton mobility accessible by solid-state NMR and bulk proton conductivity is
      complex. Improvements through admixture of a second component with protogenic
      groups are suggested.

PMID- 19385595
TI  - From yellow rain to green wheat: 25 years of trichothecene biosynthesis research.
AB  - Trichothecene biosynthesis research at the U.S. Department of Agriculture in
      Peoria, IL, began in 1984 in response to concerns about the use of trichothecenes
      in biological warfare, but continued as a long-term research program on the
      intractable problem of trichothecene contamination of human foods and animal
      feeds. Over 25 years, the trichothecene biosynthesis research group integrated
      natural product chemistry with fungal genetics and plant pathology in the
      laboratory and in the field to understand how and why Fusarium species make these
      complex and highly toxic metabolites. This interdisciplinary research placed
      trichothecenes in the unique class of fungal metabolites that not only cause
      mycotoxicoses in animals but also are virulence factors in plant disease.

PMID- 19385596
TI  - Gas chromatography-mass spectrometry (GC-MS) characterization of volatile
      compounds in quality vinegars with protected european geographical indication.
AB  - The volatile composition of 26 premium quality vinegars belonging to three
      different protected geographical indications (traditional balsamic vinegar of
      Modena, balsamic vinegar of Modena, and sherry vinegar) has been characterized by
      means of a solid-phase extraction (SPE) gas chromatography-mass spectrometry GC
      MS method. Among the about 90 quantified compounds, short-chain fatty acids,
      furanic compounds, enolic derivatives, and some esters were found to discriminate
      the samples as a consequence of differences in the extent of Maillard reactions,
      presence of alcoholic fermentation, or duration of wood aging.

PMID- 19385597
TI  - Analysis of protein composition of red wine in comparison with rose and white
      wines by electrophoresis and high-pressure liquid chromatography-mass
      spectrometry (HPLC-MS).
AB  - Wine proteins not only influence wine stability but are also being discussed as
      potential allergens. Proteins from red, rose, and white wines were enriched by
      dialysis and lyophilization followed by separation by SDS-PAGE. Significant
      differences were detected in the protein compositions of the analyzed wine
      varieties, and the major protein bands were identified by mass spectrometry after
      in-gel digestion with trypsin. In German Portugieser red wine, a total of 121
      tryptic peptides were identified, which were attributed to 12 grape proteins and
      6 proteins derived from yeast. Among the identified constituents are several
      proteins considered to influence wine stability and previously described
      potential grape allergens. The pathogenesis-related proteins represent the main
      proteins in all of the wines, but only some red wines show a band with a
      molecular mass of 12 kDa, identified as a lipid transfer protein (LTP). The
      occurrence and distribution of LTP depend on the wine variety.

PMID- 19385598
TI  - Amyloid beta protein: Abeta40 inhibits Abeta42 oligomerization.
AB  - Abeta40 and Abeta42 are peptides that adopt similar random-coil structures in
      solution. Abeta42, however, is significantly more neurotoxic than Abeta40 and
      forms amyloid fibrils much more rapidly than Abeta40. Here, mass spectrometry and
      ion mobility spectrometry are used to investigate a mixture of Abeta40 and
      Abeta42. The mass spectrum for the mixed solution shows the presence of a
      heterooligomer composed of equal parts of Abeta40 and Abeta42. Ion mobility
      results indicate that this mixed species comprises an oligomer distribution
      extending to tetramers. Abeta40 alone produces such a distribution, whereas
      Abeta42 alone produces oligomers as large as dodecamers. This indicates that
      Abeta40 inhibits Abeta42 oligomerization.

PMID- 19385600
TI  - Synthesis and modeling of new benzofuranone histone deacetylase inhibitors that
      stimulate tumor suppressor gene expression.
AB  - New benzofuranones were synthesized and evaluated toward NCI-H661 non-small cell
      lung cancer cells. Benzamide derivatives possessed micromolar antiproliferative
      and histone deacetylase inhibitory activities and modulate histone H4
      acetylation. Hydroxamic acids were found to be potent nanomolar antiproliferative
      agents and HDAC inhibitors. Computational analysis presented a rationale for the
      activities of the hydroxamate derivatives. Impact of the HDAC inhibition on the
      expression of E-cadherin and the SEMA3F tumor suppressor genes revealed new
      promising compounds for lung cancer treatments.

PMID- 19385599
TI  - The importance of negative superhelicity in inducing the formation of G
      quadruplex and i-motif structures in the c-Myc promoter: implications for drug
      targeting and control of gene expression.
AB  - The importance of DNA supercoiling in transcriptional regulation has been known
      for many years, and more recently, transcription itself has been shown to be a
      source of this superhelicity. To mimic the effect of transcriptionally induced
      negative superhelicity, the G-quadruplex/i-motif-forming region in the c-Myc
      promoter was incorporated into a supercoiled plasmid. We show, using enzymatic
      and chemical footprinting, that negative superhelicity facilitates the formation
      of secondary DNA structures under physiological conditions. Significantly, these
      structures are not the same as those formed in single-stranded DNA templates.
      Together with the recently demonstrated role of transcriptionally induced
      superhelicity in maintaining a mechanosensor mechanism for controlling the firing
      rate of the c-Myc promoter, we provide a more complete picture of how c-Myc
      transcription is likely controlled. Last, these physiologically relevant G
      quadruplex and i-motif structures, along with the mechanosensor mechanism for
      control of gene expression, are proposed as novel mechanisms for small molecule
      targeting of transcriptional control of c-Myc.

PMID- 19385601
TI  - Diversification of a thieno[2,3-d]pyrimidin-4-one scaffold via regioselective
      alkylation reactions.
AB  - The 2-aryl-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-ones and 2
      aryl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-ones have been
      diversified by alkylation reactions, applying benzylchlorides and N-substituted 2
      chloroacetamides as alkylating agents. Under the found uniform conditions the
      substitution direction does not depend on the structure of the alkylating agent
      and gives monoalkylated products in high yields with simple workup. The
      alkylation of the 2,3-dihydropyrimidin-4(1H)-one derivatives proceeds onto the N1
      position; however, in the case of pyrimidin-4(3H)-ones the O-alkylated products
      are formed selectively. An alternative strategy for the synthesis of the N1
      benzyl-2,3-dihydropyrimidin-4(1H)-one derivatives is also developed. It applies
      the redaction of N2-substituted Gewald's amides with aromatic aldehydes and
      allows simple introduction of various substituents in the final molecule.

PMID- 19385602
TI  - Novel fluorescent cationic silver thiosemicarbazone clusters containing different
      eight-membered Ag(4)S(4) metallacycles.
AB  - The reaction of silver acetate and silver nitrate with the new
      phosphinethiosemicarbazone ligand 2-(2-(diphenylphosphino)benzylidene)-N
      ethylthiosemicarbazone (HLPEt) gave rise to the complexes [Ag(LPEt)](4).2MeOH (1)
      and [Ag(2)(LPEt)(HLPEt)](2).(NO(3))(2) (3). Slow crystallization of the mother
      liquors obtained from the synthesis of 1 and 3 afforded suitable crystals of
      [Ag(2)(LPEt)(HLPEt)](2)(CH(3)COO)(2).6MeOH (2) and
      [Ag(2)(LPEt)(HLPEt)](2)(NO(3))(2).2MeOH.2H(2)O (4), respectively. Complexes 2 and
      4 are tetranuclear silver clusters displaying a similar Ag(4)S(4)P(4) core, but
      containing different sizes, conformations for the Ag(4)S(4) metallacycles, and
      crystal packings. The four complexes are strongly luminescent in methanol
      solutions. A comparison between the emission bands of compounds 1-4 lead us to
      conclude that the luminescence is notably affected by the charge and the
      counterion of the cluster.

PMID- 19385603
TI  - Crucial role of conserved cysteine residues in the assembly of two iron-sulfur
      clusters on the CIA protein Nar1.
AB  - Iron-sulfur (Fe/S) protein maturation in the eukaryotic cytosol and nucleus
      requires conserved components of the essential CIA machinery. The CIA protein
      Nar1 performs a specific function in transferring an Fe/S cluster that is
      assembled de novo on the Cfd1-Nbp35 scaffold to apoproteins. Here, we used
      systematic site-directed mutagenesis and a combination of in vitro and in vivo
      studies to show that Nar1 holds two Fe/S clusters at conserved N- and C-terminal
      cysteine motifs. A wealth of biochemical studies suggests that the assembly of
      these Fe/S clusters on Nar1 cannot be studied in Escherichia coli, as the
      recombinant protein does not contain the native Fe/S clusters. We therefore
      followed Fe/S cluster incorporation directly in yeast by a (55)Fe radiolabeling
      method in vivo, and we measured the functional consequences of Nar1 mutations in
      the assembly of cytosolic Fe/S proteins. We find that both Fe/S clusters are
      essential for Nar1 function and cell viability. Molecular modeling using a
      structurally but not functionally related bacterial iron-only hydrogenase as a
      template provided compelling structural explanations for our mutational data. The
      C-terminal Fe/S cluster is stably buried within Nar1, whereas the N-terminal one
      is exposed at the protein surface and hence may be more easily lost. Insertion of
      an Fe/S cluster into the C-terminal location depends on the N-terminal motif,
      suggesting the participation of the latter motif in the assembly process of the C
      terminal cluster. The vicinity of the two Fe/S centers suggests a close
      functional cooperation during cytosolic Fe/S protein maturation.

PMID- 19385604
TI  - Dielectric properties of water inside single-walled carbon nanotubes.
AB  - In this paper, we report novel ferroelectric properties of a new form of ice
      inside single-walled carbon nanotubes (SWCNTs). These are called "ice nanotubes"
      (ice NTs) and they consist of polygonal water rings stacked one-dimensionally
      along the SWCNT axis. We performed molecular dynamics (MD) calculations for the
      ice NTs under an external electric field and in a temperature range between 100
      and 350 K. It is revealed that ice NTs show stepwise polarization with a
      significant hysteresis loop as a function of the external field strength. In
      particular, pentagonal and heptagonal ice NTs are found to be the world's
      smallest ferroelectrics with spontaneous polarization of around 1 microC/cm(2).
      The n-gonal ice NT, where n = 5, 6, or 7, has (n + 1)-polarized structures with
      different polarizations. These findings suggest potential applications of SWCNTs
      encapsulating dielectric materials for the fabrication of the smallest
      ferroelectric devices. Experimental evidence for the presence of ice NTs inside
      SWCNTs is also discussed in great detail.

PMID- 19385605
TI  - A common mechanism underlies the dark fraction formation and fluorescence
      blinking of quantum dots.
AB  - CdSe quantum dots (QDs) are known to exhibit both power-law blinking dynamics and
      a dark fraction. A complete description of the mechanistic origins of these
      properties is still lacking. We show that a change in the pH of the QD
      environment systematically changes both the dark fraction and the blinking
      statistics. As pH is lowered, shorter "on" times and longer "off" times, as well
      as an increase in the permanent dark fraction, are observed. The increase in the
      dark fraction is preceded by a decrease in the emission intensity of a single QD.
      Interestingly, the form of the probability distribution function describing
      blinking changes when the QDs are taken from an air-exposed environment into an
      aqueous one. These results are used to propose a coupled role for H(+) ions by
      which they first reduce the intensity of the emitting state as well as affect the
      probabilities of the QD to switch between "on" and "off" states and eventually
      trap the QD in a permanent "off" state. We discuss and extend two theoretical
      blinking models to account for the effect of H(+) ions as well as to highlight
      their common principle of a diffusion-controlled mechanism governing blinking.

PMID- 19385606
TI  - One-pot synthesis of N-arylpyrazoles from arylhalides.
AB  - A simple one-pot method for the synthesis of diversely functionalized pyrazoles
      from aryl nucleophiles, di-tert-butylazodicarboxlate, and 1,3-dicarbonyl or
      equivalent compounds is presented.

PMID- 19385607
TI  - Organocatalytic enantioselective Friedel-Crafts alkylation of 4,7-dihydroindoles
      with alpha,beta-unsaturated aldehydes: an easy access to 2-substituted indoles.
AB  - An enantioselective Friedel-Crafts alkylation of 4,7-dihydroindoles and
      alpha,beta-unsaturated aldehydes has been developed. The process is promoted by
      diphenylprolinol ether to afford 2-substituted 4,7-dihydroindoles in high yields
      and enantioselectivities. After a subsequent oxidation of the products, the
      optically active 2-substituted indoles could be obtained smoothly in high yields
      without any loss of enantioselectivity.

PMID- 19385608
TI  - Generation of ortho-quinone methides by p-TsOH on silica and their hetero-Diels
      Alder reactions with styrenes.
AB  - 2-Arylchromans were readily prepared from the hetero-Diels-Alder reactions of
      styrenes with the ortho-quinone methides (o-QMs) which, in turn, were generated
      by treating the MOM-protected benzylacetate derivatives with p-TsOH immobilized
      on silica (PTS-Si) in toluene under mild conditions (0 degrees C to rt). The
      corresponding chromans were obtained in moderate to excellent yields (42-97%) and
      in moderate to excellent diastereoselectivity (up to >99:1).

PMID- 19385609
TI  - One-pot syntheses of dissymmetric diamides based on the chemistry of cyclic
      monothioanhydrides. Scope and limitations and application to the synthesis of
      glycodipeptides.
AB  - Opening cyclic monothioanhydrides by amines provides a convenient entry into
      amido thioacids that can be trapped in situ by 2,4-dinitrobenzenesulfonamides, by
      electron-deficient azides, or by amines in the presence of Sanger's reagent
      leading, in each case, to dissymmetric diamides in what can be considered a one
      pot, three-component coupling sequence. The use of monothiomaleic anhydride and
      bifunctional nucleophiles such as amino thiols provides access to heterocyclic
      amides. The low reactivity of cyclic monothioanhydrides toward alcohols enables
      the use of methanol as solvent and obviates the need for the protection of
      alcohols in the various reaction components. Reaction of N-benzyloxycarbonyl-l
      aspartic monothioanhydride with unprotected glycosyl amines, followed by capture
      of the thioacid intermediate with N-sulfonyl amino acid derivatives results in a
      three-component convergent synthesis of glycosylated peptides.

PMID- 19385610
TI  - A direct and efficient total synthesis of the tubulin-binding agents ceratamine A
      and B; use of IBX for a remarkable heterocycle dehydrogenation.
AB  - The total synthesis of the tubulin-binding agents ceratamine A and B is reported,
      along with des-methyl analogs, via a synthetic route that is high-yielding and
      operationally efficient. The synthetic route involved a Beckmann rearrangement to
      form an azepine ring precursor, a Knoevenagel condensation to install the
      benzylic side chain, and an effective imidazole annulation onto an alpha
      aminoketone precursor with a protected S-methylisothiourea. Final dehydrogenation
      proved remarkably facile using IBX.

PMID- 19385611
TI  - Synthesis of dibenz[b,f]oxepins via manganese(III)-based oxidative 1,2-radical
      rearrangement.
AB  - The oxidation of monoalkyl 2-(9H-xanthenyl)malonates 1 with Mn(OAc)(3) gave the 9
      or 10-dibenz[b,f]oxepincarboxylates 2 in good yields. The reaction proceeds with
      high regioselectivity except for the case of (1-methoxyxanthenyl)malonate 1 (R(1)
      = Me, R(2) = 1-MeO), which gave two regioisomers. It was proposed that the
      process for the formation of 2 must include the 1,2-aryl radical rearrangement
      followed by oxidative decarboxylation.

PMID- 19385612
TI  - Mixed micelles of Triton X-100, sodium dodecyl dioxyethylene sulfate, and
      synperonic l61 investigated by NOESY and diffusion ordered NMR spectroscopy.
AB  - Mixed micelles formed from nonionic surfactant Triton X-100 (TX100), anionic
      surfactant sodium dodecyl dioxyethylene sulfate (SDP2S), and triblock copolymer
      Synperonic L61 (SL61) were investigated by 1H NMR spectroscopy. The size and
      shape of the aggregates were determined by diffusion ordered NMR spectroscopy
      (DOSY), while 2D nuclear Overhauser enhanced spectroscopy (NOESY) NMR was used to
      study the mutual spatial arrangement of the surfactant molecules in the
      aggregated state. An average micellar hydrodynamic radius of 3.6 nm, slightly
      increasing upon increasing TX100 molar fraction, was found for the mixed systems
      without additives. Addition of SL61 to the mixed micellar systems results in a
      slight increase of micellar radii. In the presence of AlCl3, an increase of
      TX100/SDP2S micellar sizes from 4 to 10 nm was found when increasing the SDP2S
      molar fraction. The mixed TX100/SDP2S micelles in the presence of both AlCl3 and
      polymer SL61 are almost spherical, with a radius of 4.5 nm. 2D NOESY data reveal
      that, as the individual TX100 micelles, mixed TX100/SDP2S and
      TX100/SDP2S/SL61/AlCl3 micelles also have a multilayer structure, with partially
      overlapping internal and external layers of TX100 molecules. In these mixed
      micelles, the SDP2S molecules are located at the level of the external layer of
      TX100 molecules, whereas the SL61 polymer is partially incorporated inside of the
      micellar core.

PMID- 19385613
TI  - Human glucagon receptor antagonists with thiazole cores. A novel series with
      superior pharmacokinetic properties.
AB  - The aim of the work presented here was to design and synthesize potent human
      glucagon receptor antagonists with improved pharmacokinetic (PK) properties for
      development of pharmaceuticals for the treatment of type 2 diabetes. We describe
      the preparation of compounds with cyclic cores (5-aminothiazoles), their binding
      affinities for the human glucagon and GIP receptors, as well as affinities for
      rat, mouse, pig, dog, and monkey glucagon receptors. Generally, the compounds had
      slightly less glucagon receptor affinity compared to compounds of the previous
      series, but this was compensated for by much improved PK profiles in both rats
      and dogs with high oral bioavailabilities and sustained high plasma exposures.
      The compounds generally showed species selectivity for glucagon receptor binding
      with poor affinities for the rat, mouse, rabbit, and pig receptors. However, dog
      and monkey glucagon receptor affinities seem to reflect the human situation. One
      compound of this series, 18, was tested intravenously in an anesthetized glucagon
      challenged monkey model of hyperglucagonaemia and hyperglycaemia and was shown
      dose-dependently to decrease glycaemia. Further, high plasma exposures and a long
      plasma half-life (5.2 h) were obtained.

PMID- 19385614
TI  - Large-scale application of high-throughput molecular mechanics with Poisson
      Boltzmann surface area for routine physics-based scoring of protein-ligand
      complexes.
AB  - We apply a high-throughput formulation of the molecular mechanics with Poisson
      Boltzmann surface area (htMM-PBSA) to estimate relative binding potencies on a
      set of 308 small-molecule ligands in complex with the proteins urokinase, PTP-1B,
      and Chk-1. We observe statistically significant correlation to experimentally
      measured potencies and report correlation coefficients for the three proteins in
      the range 0.72-0.83. The htMM-PBSA calculations illustrate the feasibility of
      procedural automation of physics-based scoring calculations to produce rank
      ordered binding-potency estimates for protein-ligand complexes, with sufficient
      throughput for realization of practical implementation into scientist workflows
      in an industrial drug discovery research setting.

PMID- 19385615
TI  - On the synergism between H2O and a tetrahydropyran template in the regioselective
      cyclization of an epoxy alcohol.
AB  - A regioselective epoxy alcohol cyclization promoted by the combination of neutral
      water and a tetrahydropyran template was investigated through a series of
      mechanistic experiments carried out on an epoxy alcohol containing a
      tetrahydropyran ring (1a) and its carbocyclic congener (1b). In contrast to 1a,
      cyclizations of 1b were unselective and displayed significantly faster reaction
      rates suggesting that the tetrahydropyran oxygen in 1a is requisite for
      regioselective cyclization. Reactions for both substrates were shown to occur in
      solution and under kinetic control without significant influence from hydrophobic
      effects. Kinetic measurements carried out in water/dimethyl sulfoxide mixtures
      suggest that 1b reacts exclusively through an unselective pathway requiring one
      water molecule more than what is required to solvate the epoxy alcohol. Similar
      experiments for 1a suggest a competition between an unselective and a selective
      pathway requiring one and two water molecules in excess of those required to
      solvate 1a, respectively. The selective pathway observed for 1a but not in 1b is
      rationalized by electronic and conformational differences between the two
      compounds.

PMID- 19385616
TI  - Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces
      coelicolor. Mechanism and stereochemistry of the enzymatic formation of epi
      isozizaene.
AB  - Epi-isozizaene synthase from Streptomyces coelicolor catalyzes the multistep
      cyclization of farnesyl diphosphate (2, FPP) to the tricyclic sesquiterpene
      hydrocarbon (+)-epi-isozizaene (3), which is converted in turn to the antibiotic
      albaflavenone (1) in a two-step, cytochrome P450-catalyzed oxidation. Competitive
      incubation of deuterated and nondeuterated samples of (3S)-NPP and (3RS)-NPP
      followed by GC-MS analysis of the degree of deuteration in the resulting labeled
      epi-isozizaene established that (3R)-NPP is the natural cyclization intermediate.
      Incubation of (3RS)-(Z)-[1-(2)H]NPP (4b) with epi-isozizaene synthase gave
      [11(anti)-(2)H]epi-isozizaene (3b), indicating that the S(N)' cyclization of 4
      involves the predicted anti stereochemistry, consistent with the inference from
      earlier experiments with chirally deuterated FPP. Incubation of separate samples
      of [12,12,12-(2)H(3)]FPP (2d) and [13,13,13-(2)H(3)]FPP (2e) gave epi-isozizaenes
      3d and 3e, thereby establishing the stereochemical course of the cyclization of
      the proposed intermediate acorenyl cation 6, as well as the stereochemistry of
      the successive 1,2-methyl migration and deprotonation that generate the final
      product. Further insights into the mechanism and the role of the enzyme came from
      site-directed mutagenesis of active site residues in two universally conserved
      Mg(2+)-binding domains and the identification of six minor sesquiterpene products
      9-13 and 15 produced by the wild-type and mutant proteins. The aberrant products
      are believed to result from derailment and premature quenching of the normal
      intermediates of the cationic cyclization cascade.

PMID- 19385617
TI  - Decamethylytterbocene complexes of bipyridines and diazabutadienes:
      multiconfigurational ground states and open-shell singlet formation.
AB  - Partial ytterbium f-orbital occupancy (i.e., intermediate valence) and open-shell
      singlet formation are established for a variety of bipyridine and diazabutadiene
      adducts with decamethylytterbocene, (C(5)Me(5))(2)Yb, abbreviated as Cp*(2)Yb.
      Data used to support this claim include ytterbium valence measurements using Yb
      L(III)-edge X-ray absorption near-edge structure spectroscopy, magnetic
      susceptibility, and complete active space self-consistent field (CASSCF)
      multiconfigurational calculations, as well as structural measurements compared to
      density functional theory calculations. The CASSCF calculations indicate that the
      intermediate valence is the result of a multiconfigurational ground-state wave
      function that has both an open-shell singlet f(13)(pi*)(1), where pi* is the
      lowest unoccupied molecular orbital of the bipyridine or diazabutadiene ligands,
      and a closed-shell singlet f(14) component. A number of other competing theories
      for the unusual magnetism in these materials are ruled out by the lack of
      temperature dependence of the measured intermediate valence. These results have
      implications for understanding chemical bonding not only in organolanthanide
      complexes but also for f-element chemistry in general, as well as understanding
      magnetic interactions in nanoparticles and devices.

PMID- 19385618
TI  - Passing two strings through the same ring using an octahedral metal center as
      template: a new synthesis of [3]rotaxanes.
AB  - Octahedral transition metal centers such as Fe(II), Co(II), and Co(III) have been
      used as templates in the construction of [3]pseudorotaxanes and [3]rotaxanes from
      various acyclic and macrocyclic fragments. The species obtained consist of a ring
      threaded by two string-like compounds. Such systems are relatively uncommon in
      the [3]rotaxane family, the most usual form being made up of a single axis
      threaded through two rings. The key structural feature of the present systems is
      the coordinating unit incorporated in the various organic fragments and used in
      conjunction with the metal to gather and thread the two filaments through the
      ring. This bidentate chelate is derived from 8,8'-diphenyl-3,3'-bi-isoquinoline,
      a very rare example of an endotopic but nonsterically hindering ligand. The
      stoppered [3]rotaxanes were obtained by using an open-chain fragment bearing
      azide groups as end functions, followed by click chemistry using a propargyl
      ether attached to a very bulky group. A particularly attractive X-ray structure
      was obtained for a cobalt(III)-complexed [3]pseudorotaxane consisting of a 41
      membered ring and two crescent-shaped threaded components. The Fe(II) and Co(III)
      complexes were characterized by (1)H NMR and ES-MS. By taking advantage of the
      markedly different kinetic properties of the two oxidation states, Co(II) and
      Co(III), it was possible to proceed to fast coordination or decoordination
      reactions (for the divalent state) or, when needed, to "freeze" the complexes due
      to the kinetic inertness of the trivalent state and to study them by (1)H NMR.
      Finally, demetalation of the two stoppered compounds prepared was performed. This
      demetalation reaction was fast for the Co(II)-complexed [3]rotaxane, whereas
      decomplexation of the Fe(II) equivalent required harsh conditions which were not
      compatible with the stability of the metal-free rotaxane. Interestingly, the
      thermal stability of the free [3]rotaxane toward unthreading and formation of its
      constitutive elements was only limited. (1)H NMR measurements showed that the
      half-life of the rotaxane is about one week at room temperature in
      dichloromethane. A variable-temperature study revealed that the unthreading
      reaction leading to dissociation of the [3]rotaxane has a remarkably high entropy
      of activation, in agreement with the intuitive view that the unthreading process
      involves a highly ordered transition state.

PMID- 19385620
TI  - Locked nucleic acid (LNA)-modified dinucleotide mRNA cap analogue: synthesis,
      enzymatic incorporation, and utilization.
AB  - There has been considerable therapeutic interest in the development of human
      vaccines against cancers and infectious diseases such as HIV and biowarfare
      agents by using transfected mRNAs for antigenic proteins of interest. The highest
      expression levels of these proteins are obtained when the transfected mRNA
      contains 5'-capped ends. In the present study, the locked nucleic acid (LNA)
      modified cap analogue 3, m(7(LNA))G[5']ppp[5']G, has been synthesized and its
      biological properties were examined. The LNA-modified cap analogue was an
      efficient substrate for T7 RNA polymerase, and the mRNA transcribed, with a
      poly(A) tail, was efficiently utilized in an in vitro translation process. The
      RNA with the 5'-LNA-modified cap was found to be approximately 1.61- and 1.28
      fold more stable than the RNA with the 5'-standard 4 and ARCA cap, respectively,
      and approximately 4.23-fold more stable than the uncapped control RNA. The RNA
      capped with the m(7(LNA))G[5']ppp[5']G 3 cap analogue was translated the most
      efficiently, with approximately 3.2-fold more activity than the standard cap,
      m(7)G[5']ppp[5']G 4. Furthermore, we have developed a nonradioactive analytical
      HPLC assay to determine that the LNA-modified 3 cap analogue was incorporated
      solely into the forward orientation. Molecular modeling of the
      m(7(LNA))G[5']ppp[5']G 3 cap analogue with the cap binding protein elF4E complex
      indicates that the LNA-modified cap-protein complex is more stable by 47.28
      kcal/mol as compared to the standard mCAP-protein complex. These findings suggest
      that the new antireverse cap analogue m(7(LNA))G[5']ppp[5']G 3 is a potential
      candidate for RNA-based therapeutic vaccine production as well as studying
      biochemical processes.

PMID- 19385619
TI  - Evolution of a histone H4-K16 acetyl-specific DNA aptamer.
AB  - We report the in vitro selection of DNA aptamers that bind to histone H4 proteins
      acetylated at lysine 16. The best aptamer identified in this selection binds to
      the target protein with a K(d) of 21 nM and discriminates against both the
      nonacetylated protein and histone H4 proteins acetylated at lysine 8. Comparative
      binding assays performed with a chip-quality antibody reveal that this aptamer
      binds to the acetylated histone target with similar affinity to a commercial
      antibody but shows significantly greater specificity (15-fold versus 2400-fold)
      for the target molecule. This result demonstrates that aptamers that are both
      modification and location specific can be generated to bind specific protein post
      translational modifications.

PMID- 19385621
TI  - Charge and temperature dependence of biomolecule conformations: K+
      tryptamine(H2O)(n=0-1)Ar(m=0-1) cluster ions.
AB  - The impact of temperature and charge on the conformation of tryptamine (Tryp) is
      examined in the gas phase by infrared laser-vibrational predissociation
      spectroscopy in the 2800-3800 cm(-1) region. Previous studies of neutral
      Tryp(H(2)O)(n) clusters showed preferential stabilization of specific tryptamine
      conformers through hydrogen bonding. When complexed with the biologically
      significant potassium ion, the only conformers found to form under these
      experimental conditions are built on hitherto unobserved neutral Tryp conformers.
      The electrostatic interaction between K(+), the tryptamine NH(2) lone pair, and
      the indole ring in K(+)(Tryp) favors the formation of these new conformers. The
      observed K(+)(Tryp)(H(2)O) conformers vary significantly from the previously
      reported neutral Tryp(H(2)O) structure. Using the argon tagging method, we show
      how variations in temperature impact the observed infrared spectra, demonstrating
      that different conformers are populated under the different experimental
      conditions. In addition, the presence of a high-energy conformer of
      K(+)(Tryp)(H(2)O), trapped by the argon evaporative cooling process, was
      identified. Exploring the conformational landscape of hydrated cluster ions
      bearing flexible biomolecules is now possible.

PMID- 19385622
TI  - Thermal expansion matching via framework flexibility in zinc dicyanometallates.
AB  - The thermal expansion properties of two isostructural zinc dicyanometallates that
      crystallize with and without the inclusion of a weakly interacting secondary
      crystalline phase have been investigated using variable temperature single
      crystal and powder X-ray diffraction. The guest-free Zn[Au(CN)(2)](2) framework
      was found to show very strong anisotropic positive and negative thermal
      expansion. In contrast, its cocrystal analogue Zn[Ag(CN)(2)](2) x xAgCN exhibited
      much more moderate behavior, such that the coefficient of thermal expansion for
      the host Zn[M(CN)(2)](2) framework now matched that of crystalline AgCN. It was
      proposed that this correlation points to a more general ability of highly
      flexible framework materials to "match" the thermal expansivity of adhered phases
      (e.g., substrates, sorbates, or cocrystallized species), suggesting a methodology
      of eliminating thermal strain in multicomponent assemblies.

PMID- 19385623
TI  - Lack of visible chromophore development in the pulse radiolysis oxidation of 5,6
      dihydroxyindole-2-carboxylic acid oligomers: DFT investigation and implications
      for eumelanin absorption properties.
AB  - The structural factors underlying the peculiar optical properties and visible
      chromophore of eumelanin biopolymers are largely uncharted. It is known that
      synthetic eumelanins from 5,6-dihydroxyindole are black and display a featureless
      UV-visible absorption spectrum, whereas those from 5,6-dihydroxyindole-2
      carboxylic acid (1) are lighter in color and exhibit a distinct band around 310
      nm, but the origin of this difference has never been addressed in detail.
      Recently, we showed that 5,6-dihydroxyindole dimers generate on pulse radiolysis
      oxidation strongly absorbing transients with intense maxima in the 500-600 nm
      region, which have been attributed to planar extended quinone methide species. We
      now report the unexpectedly different behavior of three oligomers from 1, namely,
      the 4,4'-biindolyl 2, the 4,7'-biindolyl 3, and the 4,7':4',7''-terindolyl 4.
      Pulse radiolysis oxidation of 2-4 led initially to semiquinone intermediates
      exhibiting similar absorption maxima at 360-380 nm. Semiquinone absorption decay
      followed second-order kinetics (2k = 1.4 x 10(8), 3.2 x 10(8), and 1.4 x 10(8) M(
      1) s(-1) for 2, 3, and 4, respectively) but did not lead to significant
      chromophore development in the visible region. Similar absorption traces were
      obtained from monomer 1. DFT calculations predicted 5,6-dihydroxyindolyl-5,6
      indolequinone structures with significant dihedral twists across the interunit
      single bonds for the most stable two-electron oxidation products of 2 and 3. The
      computed absorption spectra consistently featured strong bands around 310 nm but
      little or no absorption in the visible region. It is suggested that the effective
      conjugation length in oligomeric/polymeric eumelanin components from 1 may be
      controlled by hindered rotation around inter-ring bonds preventing planarization
      of the continuous array of indole units. This may provide an explanation for the
      difference in the absorption properties of polymers from the two key eumelanin
      monomers.

PMID- 19385624
TI  - Technique for ultrathin layer chromatography using an electrospun, nanofibrous
      stationary phase.
AB  - A technique for creating devices for ultrathin layer chromatography (UTLC) using
      an electrospinning method is described. The devices use a nanofibrous stationary
      phase with fiber diameters that are 400 nm. Separations of mixtures of laser dyes
      and mixtures of steroidal compounds were performed to illustrate the capabilities
      of these new UTLC media. The complete analyses were found to require very little
      development time and require less solvent than typical TLC methods. The
      efficiency of the separations was substantially improved compared to that
      determined using commercial phases. The retention properties and efficiency of
      the technique are discussed as are the effects of mat thickness and mobile phase
      composition on the chromatographic properties of the devices.

PMID- 19385625
TI  - A nanocube plasmonic sensor for molecular binding on membrane surfaces.
AB  - Detection and characterization of molecular interactions on membrane surfaces is
      important to biological and pharmacological research. Here, silver nanocubes
      interfaced with glass-supported model membranes form a label-free sensor that
      measures protein binding to the membrane. The technique utilizes plasmon
      resonance scattering of nanocubes, which are chemically coupled to the membrane.
      In contrast to other plasmonic sensing techniques, this method features simple,
      solution-based device fabrication and readout. Static and dynamic
      protein/membrane binding are monitored and quantified.

PMID- 19385626
TI  - Theoretical and experimental studies of the conversion of chromopyrrolic acid to
      an antitumor derivative by cytochrome P450 StaP: the catalytic role of water
      molecules.
AB  - Chromopyrrolic acid (CPA) oxidation by cytochrome P450 StaP is a key process in
      the biosynthesis of antitumor drugs (Onaka, H.; Taniguchi, S.; Igarashi, Y.;
      Furumai, T. Biosci. Biotechnol. Biochem. 2003, 67, 127-138), which proceeds by an
      unusual C-C bond coupling. Additionally, because CPA is immobilized by a hydrogen
      bonding array, it is prohibited from undergoing direct reaction with Compound I,
      the active species of P450. As such, the mechanism of P450 StaP poses a puzzle.
      In the present Article, we resolve this puzzle by combination of theory, using
      QM/MM calculations, and experiment, using crystallography and reactivity studies.
      Theory shows that the hydrogen-bonding machinery of the pocket deprotonates the
      carboxylic acid groups of CPA, while the nearby His(250) residue and the crystal
      waters, Wat(644) and Wat(789), assist the doubly deprotonated CPA to transfer
      electron density to Compound I; hence, CPA is activated toward proton-coupled
      electron transfer that sets the entire mechanism in motion. The ensuing mechanism
      involves a step of C-C bond formation coupled to a second electron transfer, four
      proton-transfer and tautomerization steps, and four steps where Wat(644) and
      Wat(789) move about and mediate these events. Experiments with the dichlorinated
      substrate, CCA, which expels Wat(644), show that the enzyme loses its activity.
      H250A and H250F mutations of P450 StaP show that His(250) is important, but in
      its absence Wat(644) and Wat(789) form a hydrogen-bonding diad that mediates the
      transformation. Thus, the water diad emerges as the minimal requisite element
      that endows StaP with function. This highlights the role of water molecules as
      biological catalysts that transform a P450 to a peroxidase-type (Derat, E.;
      Shaik, S. J. Am. Chem. Soc. 2006, 128, 13940-13949).

PMID- 19385627
TI  - Emission mechanism of doubly ortho-linked quinoxaline/diphenylfluorene or cis
      stilbene/fluorene hybrid compounds based on the transient absorption and emission
      measurements during pulse radiolysis.
AB  - A series of bipolar OLED materials were subjected to pulsed radiolysis
      experiments to determine their transient absorption and lifetime profiles of the
      independently in situ generated radical cations and anions in solutions.
      Moreover, their emission behaviors from the charge recombination of their radical
      ions were also determined by the pulse radiolysis method. It was found the
      absorption bands in doubly ortho-linked quinoxaline/diphenylfluorene hybrids 1a-e
      are red-shifted progressively with increasing electron-donating nature at the C5
      and C8 positions of the quinoxaline template. The incipient radical anions in 1a
      e are mainly localized on the quinoxaline heterocyclic moiety, whereas the
      incipient radical cations are mainly distributed onto the attached electron
      donating groups at the C5 and C8 positions of the quinoxaline template. For other
      doubly ortho-linked cis-stilbene derivatives 3d, 3f, and 4f, the radical anions
      are mainly localized on the cis-stilbene central moiety and the radical cation is
      mainly distributed onto both para substituents of the cis-stilbene templates. It
      was also shown that there is a correlation between their optoelectronic emission
      efficiencies and the radiolysis induced emission intensities. In addition, the
      charge transporting behaviors within an OLED device were found to show the
      relationship with transient absorption half-lives (tau(1/2)) of the radical ions.
      Charge recombination mechanisms in both the OLED and pulsed radiolysis
      experiments were proposed to rationalize these observations, allowing us to
      establish some guidelines for an ultimate molecular design of ideal bipolar
      optoelectronic materials with a judicious choice of local charge appendages in
      the optoelectronic templates.

PMID- 19385628
TI  - Dynamic measurements of aqueous lanthanide triflate-catalyzed reactions using
      luminescence decay.
AB  - There is tremendous interest in water-compatible lanthanide triflate-based
      catalysts for carbon-carbon bond forming reactions; however, poor understanding
      of their aqueous mechanism severely limits the ability to increase the utility of
      these catalysts. Here, we report dynamic measurements of the water-coordination
      number of lanthanide triflate-based catalysts using luminescence-decay
      measurements in a range of aqueous systems. This unique characterization method
      is a reliable, convenient, and fast approach to analyze lanthanide-based
      catalysts in aqueous systems.

PMID- 19385629
TI  - Magnetic resonance imaging studies on catalyst impregnation processes:
      discriminating metal ion complexes within millimeter-sized gamma-Al2O3 catalyst
      bodies.
AB  - Magnetic resonance imaging (MRI) was used to study the impregnation step during
      the preparation of Ni/gamma-Al(2)O(3) hydrogenation catalysts with Ni(2+) metal
      ion present in different coordinations. The precursor complexes were
      [Ni(H(2)O)(6)](2+) and [Ni(edtaH(x))]((2-x)-) (where x = 0, 1, 2 and edta =
      ethylenediaminetetraacetic acid), representing a nonshielded and a shielded
      paramagnetic complex, respectively. Due to this shielding effect of the ligands,
      the dynamics of [Ni(H(2)O)(6)](2+) or [Ni(edtaH(x))]((2-x)-) were visualized
      applying T(2) or T(1) image contrast, respectively. MRI was applied in a
      quantitative manner to calculate the [Ni(H(2)O)(6)](2+) concentration
      distribution after impregnation when it was present alone in the impregnation
      solution, or together with the [Ni(edtaH(x))]((2-x)-) species. Moreover, the
      combination of MRI with UV-vis microspectroscopy allowed the visualization of
      both species with complementary information on the dynamics and
      adsorption/desorption phenomena within gamma-Al(2)O(3) catalyst bodies. These
      phenomena yielded nonuniform Ni distributions after impregnation, which are
      interesting for certain industrial applications.

PMID- 19385630
TI  - Polar or nonpolar? A+ cation polarity control in A2Ti(IO3)6 (A = Li, Na, K, Rb,
      Cs, Tl).
AB  - We have synthesized a series of new alkali-metal or Tl(+) titanium iodates,
      A(2)Ti(IO(3))(6) (A = Li, Na, K, Rb, Cs, Tl). Interestingly the Li and Na phases
      are noncentrosymmetric (NCS) and polar, whereas the K, Rb, Cs, and Tl analogues
      are centrosymmetric (CS) and nonpolar. We are able to explain the change from NCS
      polar to CS nonpolar using cation-size arguments, coordination requirements, and
      bond valence concepts. The six materials are topologically similar, consisting of
      TiO(6) octahedra, each of which is bonded to six IO(3) polyhedra. These
      polyhedral groups are separated by the A(+) cations. Our calculations on
      Na(2)Ti(IO(3))(6) indicate that polarization reversal is energetically very
      unfavorable, rendering the material polar but not ferroelectric. For all of the
      materials, synthesis, structural characterization, electronic structure analysis,
      infrared spectra, UV-vis and thermogravimetric measurements, and ion-exchange
      reactions are reported. For the polar materials, second-harmonic generation,
      piezoelectricity, and polarization measurements were performed. Crystal data:
      Li(2)Ti(IO(3))(6): hexagonal, space group P6(3) (No. 173), a = b = 9.3834(11) A,
      c = 5.1183(6) A, Z = 1. Na(2)Ti(IO(3))(6): hexagonal, space group P6(3) (No.
      173), a = b = 9.649(3) A, c = 5.198(3) A, Z = 1. K(2)Ti(IO(3))(6): trigonal,
      space group R3 (No. 148), a = b = 11.2703(6) A, c = 11.3514(11) A, Z = 3.
      Rb(2)Ti(IO(3))(6): trigonal, space group R3 (No. 148), a = b = 11.3757(16) A, c =
      11.426(3) A, Z = 3. Cs(2)Ti(IO(3))(6): trigonal, space group R3 (No. 148), a = b
      = 11.6726(5) A, c = 11.6399(10) A, Z = 3. Tl(2)Ti(IO(3))(6): trigonal, space
      group R3 (No. 148), a = b = 11.4167(6) A, c = 11.3953(11) A, Z = 3.

PMID- 19385631
TI  - Enhancing protein stability by adsorption onto raftlike lipid domains.
AB  - We demonstrate that the stability of adsorbed proteins can be enhanced by
      controlling the heterogeneity of the surfaceby creating raftlike domains in a
      soft liposomal membrane. Recent work has shown that enzymes adsorbed onto highly
      curved nanoscale supports can be more stable than those adsorbed on flat surfaces
      with nominally the same chemical structure. This effect has been attributed to a
      decrease in lateral interenzyme interactions on a curved surface. Exploiting this
      idea, we asked if adsorbing enzymes onto "patchy" surfaces composed of adsorbing
      and nonadsorbing regions can be used to reduce lateral interactions even on
      relatively flat surfaces. We demonstrate that creating domains on which an enzyme
      can adsorb enhances the stability of that enzyme under denaturing conditions.
      Furthermore, we demonstrate that the size of these domains has a considerable
      effect on the degree of stability imparted by adsorption. Such biomimetic raft
      inspired systems may find use in applications ranging from biorecognition to the
      design of novel strategies for the separation of biomolecules and controlling the
      interaction of multicomponent membrane-bound enzymes.

PMID- 19385632
TI  - Electric field-assisted alignment of self-assembled fibers composed of hydrogen
      bonded molecules having laterally fluorinated mesogens.
AB  - Aligned fibrous aggregates of amide compounds having laterally fluorinated
      aromatic mesogens have been successfully obtained by the application of the
      alternating current electric field (1.0 V/microm, 1 kHz) in dodecylbenzene. In
      contrast, randomly entangled fibers are formed in the solvent without electric
      fields. For the analogous compounds without fluorine substituent, no aligned
      fibrous aggregates have been obtained under the electric fields. The electric
      field alignment of the fibers should be assisted by the fluorinated rod-shaped
      mesogens that exhibit negative dielectric anisotropy.

PMID- 19385633
TI  - On the role of short and strong hydrogen bonds on the mechanism of action of a
      model chymotrypsine active site.
AB  - The electronic properties of a chemical model that mimics the His-57...Asp-102
      catalytic residues of alpha- chymotrypsine during the transition from normal
      hydrogen bond to short and strong hydrogen-bond regimes are presented. The
      results suggest that upon a global external stimulus induced by compression, the
      system response is the transfer of the nucleophilic reactivity from the model Asp
      102 moiety toward the model His-57 fragment in the hydrogen-bonded complex. In
      this way, the catalytic effect may be consistently explained on the basis of a
      pair site reactivity model framed on the second-order static density response
      function.

PMID- 19385634
TI  - Effect of surface charge on colloidal charge reversal.
AB  - The objective of this research work is to understand the effect of the surface
      charge density on the charge reversal phenomenon. To this end, we use
      experimental results and computer simulations. In particular, we measure the
      electrophoretic mobility of latex particles (macroions) in the presence of a
      multivalent electrolyte. We have focused on the electrolyte concentration range
      at which a reversal in the electrophoretic mobility is expected to happen. In
      particular, the role of the surface charge on the charge reversal process is
      looked into from several latexes with the same functional group but different
      surface charge densities. Although the mechanism responsible for the colloidal
      charge reversal is still a controversial issue, it is proved that ionic
      correlations are behind the appearance of such phenomenon (especially near the
      macroion surface). This conclusion can be inferred from a great variety of
      theoretical models. According to them, one of the factors that determine the
      charge reversal is the surface charge density of the macroions. However, this
      feature has been rarely analyzed in experiments. Our results appear therefore as
      a demanded survey to test the validity of the theoretical predictions. Moreover,
      we have also performed Monte Carlo simulations that take the ion size into
      account. The correlation found between experiments and simulations is fairly
      good. The combination of these techniques provides new insight into the colloidal
      charge reversal phenomena showing the effect of surface charge.

PMID- 19385635
TI  - NMR and pulsed field gradient NMR approach of water sorption properties in Nafion
      at low temperature.
AB  - The water uptake and the water self-diffusion coefficient were measured in Nafion
      membranes at subzero temperatures. NMR spectroscopy was used to precisely
      quantify the actual concentration of water in membranes as a function of the
      temperature and their hydration rates at room temperature. We find that below 273
      K the water concentration decreases with temperature to reach, at around 220 K, a
      limit value independent of the initial concentration. This regime is observed if
      the concentration at room temperature is higher than 10%. Below this
      concentration no membrane deswelling was observed. The water self-diffusion
      coefficient, measured by pulsed field gradient NMR in function of the
      temperature, is determined by the actual concentration C(T) whatever the
      concentration at room temperature. The concentration variation is attributed to a
      decrease in the relative humidity RH(T) of the water vapor surrounding the
      membrane induced by the simultaneous presence of supercooled water inside the
      membrane and ice outside the membrane.

PMID- 19385637
TI  - Evidence for domain motion in proteins affecting global diffusion properties: a
      nuclear magnetic resonance study.
AB  - The rotational diffusion of proteins is an important hydrodynamic property.
      Compact protein structures were found previously to exhibit hydration layer
      viscosity, etaloc, higher than the viscosity of bulk water, eta. This implies an
      apparent activation energy for rotational diffusion higher than the activation
      energy of water viscosity, Eeta=15.4+/-0.3 kJ/mol. In this study we examine
      etaloc of internally mobile proteins using 15N spin relaxation methods. We also
      examine the activation enthalpy, DeltaH#, and activation entropy, DeltaS#, for
      rotational diffusion. Of particular relevance are internally mobile ligand-free
      forms and compact ligand-bound forms of multidomain proteins. Adenylate kinase
      (AKeco) and Ca2+-calmodulin (Ca2+-CaM) are typical examples. For AKeco (Ca2+-CaM)
      we find that DeltaH# is 14.5+/-0.5 (15.7+/-0.4) kJ/mol. For the complex of AKeco
      with the inhibitor AP5A (the complex of Ca2+-CaM with the peptide smMLCKp), we
      find that DeltaH# is 18.1+/-0.7 (18.2+/-0.5) kJ/mol. The internally mobile outer
      surface protein A has DeltaH#=12.6+/-0.8 kJ/mol, and the compact protein
      Staphylococcal nuclease has DeltaH#=18.8+/-0.6 kJ/mol. For the internally mobile
      and compact proteins studied, <|DeltaS(|> equals 62+/-7 J/(mol K) and 44+/-5
      J/(mol K), respectively. The fact is that etaloc>eta (DeltaH#>Eeta) for compact
      proteins was ascribed previously to electrostatic interactions between surface
      sites and water rigidifying the hydration layer. We find herein that obliteration
      of these interactions by domain motion leads to etaloc approximately eta, DeltaH#
      approximately Eeta, and large activation entropy for internally mobile protein
      structures.

PMID- 19385636
TI  - Acetylation of vertebrate H2A.Z and its effect on the structure of the
      nucleosome.
AB  - Purified histone H2A.Z from chicken erythrocytes and a sodium butyrate-treated
      chicken erythroleukemic cell line was used as a model system to identify the
      acetylation sites (K4, K7, K11, K13, and K15) and quantify their distribution in
      this vertebrate histone variant. To understand the role played by acetylation in
      the modulation of the H2A.Z nucleosome core particle (NCP) stability and
      conformation, an extensive analysis was conducted on NCPs reconstituted from
      acetylated forms of histones, including H2A.Z and recombinant H2A.Z (K/Q)
      acetylation mimic mutants. Although the overall global acetylation of core
      histones destabilizes the NCP, we found that H2A.Z stabilizes the NCP regardless
      of its state of acetylation. Interestingly and quite unexpectedly, we found that
      the change in NCP conformation induced by global histone acetylation is dependent
      on H2A/H2A.Z acetylation. This suggests that acetylated H2A variants act
      synergistically with the acetylated forms of the core histone complement to alter
      the particle conformation. Furthermore, the simultaneous occurrence of H2A.Z and
      H2A in heteromorphic NCPs that most likely occurs in vivo slightly destabilizes
      the NCP, but only in the presence of acetylation.

PMID- 19385638
TI  - DFT study on the molecular mechanism of the [4 + 2] cycloaddition between
      thiobenzophenone and arylalkenes via radical cations.
AB  - The mechanistic aspects of the radical cationic version of the [4 + 2]
      cycloaddition between thiobenzophenone 1 and three aryl-substituted alkenes 2a-c
      have been studied using DFT methods at the UB3LYP/6-31G* level of theory. In the
      ground state, the Diels-Alder reaction follows an asynchronous concerted
      mechanism; the large activation energy associated with bond formation prevents
      this process. After generation of the radical cation (RC), formation of a
      molecular complex (MC) between 1 and 2a-c initiates a stepwise mechanism, with
      attack of the sulfur atom of 1 to the aryl-conjugated position of 2a-c.
      Subsequent ring closure is the rate-determining step of these cycloadditions.
      Methoxy or dimethylamino substitution at the aryl group, while stabilizing the
      corresponding RC, results in a less exothermic formation of MC and a significant
      increase of the cycloaddition barrier.

PMID- 19385639
TI  - Flip-flop of phospholipids in vesicles: kinetic analysis with time-resolved small
      angle neutron scattering.
AB  - We applied a time-resolved small-angle neutron scattering technique to vesicle
      systems to determine interparticle transfer and flip-flop of phospholipids.
      Measurements were performed for large unilamellar vesicles, consisting of
      dimyristoylphosphatidylcholine (DMPC), 1-palmitoyl-2-oleoylphosphatidylcholine
      (POPC), or 1-palmitoyl-2-oleoylphosphatidic acid (POPA), which differ either in
      their acyl chains or headgroup. POPC, which is analogous to naturally occurring
      phosphatidylcholines, exhibited no transbilayer transfer and very slow
      interbilayer migration. POPC on the inner leaflet of vesicles did not flop even
      when phospholipase D converted all POPC molecules on the outer leaflet into POPA,
      which was shown to exhibit fast flip-flop. From these results, together with the
      observation that the flip-flop of DMPC was entirely inhibited in the presence of
      cholesterol, it is deduced that the flip-flop of phosphatidylcholines does not
      take place spontaneously in cellular plasma membranes rich in cholesterol and
      that it requires enzymatic activities of energy-dependent and/or -independent
      flippases/floppases.

PMID- 19385640
TI  - 2009 Edward E Smissman Award. Pharmaceutical "gold" from neurostabilizing agents:
      topiramate and successor molecules.

PMID- 19385641
TI  - Noncooperative dimethyl sulfoxide-induced dissection of insulin fibrils: toward
      soluble building blocks of amyloid.
AB  - The enormous molecular weight complicates detailed structural studies of amyloid
      fibrils and obscures identification of biologically active forms of protein
      aggregates in amyloid-related diseases. Here we show that aqueous solutions of
      dimethyl sulfoxide (DMSO) solubilize insulin fibrils while maintaining their beta
      pleated structure. This is accompanied by a marked decrease in the fluorescence
      of thioflavin T. According to atomic force microscopy images and dynamic light
      scattering measurements, the partial DMSO-induced dissection of insulin fibrils
      favors formation of smaller soluble oligomers, which retain a limited capacity to
      induce daughter generation of fibrils through seeding to the native insulin, as
      well as the ability to reassemble into fibrils upon removal of DMSO through
      dialysis against water. These findings suggest that the DMSO-induced ensembles of
      insulin molecules are closely related to elementary building blocks of amyloid
      fibrils.

PMID- 19385643
TI  - Synthesis of polymer-biohybrids: from small to giant surfactants.
AB  - Amphiphiles or surfactants, more popularly known as soaps, are among the oldest
      known chemical compounds used by man. Written text on a clay tablet dated to 2200
      B.C. indicates that the Babylonians were familiar with soap-like substances.
      According to the Ebers papyrus (1550 B.C.), the ancient Egyptians bathed
      regularly in a mixture of animal oils, vegetable extracts, and alkaline salts,
      and a soap factory with bars of scented soap was found in the ruins of Pompeii
      (79 A.D.). In modern times, the use of soap has become universal, and we now
      understand reasonably well what happens when soap molecules are dispersed in
      aqueous solution and how the cleaning properties of soap work. The latter is
      related to the surface-active behavior of soap molecules, which is a result of
      their amphiphilic, also called amphipathic, character. Although the cleaning
      aspect is still an important issue, scientists are increasingly focusing on other
      properties of soaps, for example, self-assembling behavior and how this can be
      used in the design and non-covalent synthesis of new (macro)molecular
      architectures. These new molecules can be employed in nanotechnology and drug
      delivery, among other applications. This Account will focus on three different
      classes of amphiphiles. The first is the low molecular weight amphiphiles, also
      called classical amphiphiles in this context. A short overview will be given on
      the research carried out by our group and others on the self-assembly behavior
      and properties of these compounds; in particular, we focus on the ones that can
      be stabilized by polymerization (polymerized vesicles). Next, we will introduce
      the still relatively young field of superamphiphiles, macromolecules consisting
      of a hydrophobic and a hydrophilic polymeric block. Finally, and this constitutes
      the main part of this Account, we will provide an overview of a new class of
      amphiphiles, the so-called giant amphiphiles. These macromolecules have an enzyme
      or protein as the polar head group and a hydrophobic polymer as a tail. We will
      finish the Account with conclusions and an outlook to the future.

PMID- 19385644
TI  - Crystal structures of cyclohexanone monooxygenase reveal complex domain movements
      and a sliding cofactor.
AB  - Cyclohexanone monooxygenase (CHMO) is a flavoprotein that carries out the
      archetypical Baeyer-Villiger oxidation of a variety of cyclic ketones into
      lactones. Using NADPH and O(2) as cosubstrates, the enzyme inserts one atom of
      oxygen into the substrate in a complex catalytic mechanism that involves the
      formation of a flavin-peroxide and Criegee intermediate. We present here the
      atomic structures of CHMO from an environmental Rhodococcus strain bound with FAD
      and NADP(+) in two distinct states, to resolutions of 2.3 and 2.2 A. The two
      conformations reveal domain shifts around multiple linkers and loop movements,
      involving conserved arginine 329 and tryptophan 492, which effect a translation
      of the nicotinamide resulting in a sliding cofactor. Consequently, the cofactor
      is ideally situated and subsequently repositioned during the catalytic cycle to
      first reduce the flavin and later stabilize formation of the Criegee
      intermediate. Concurrent movements of a loop adjacent to the active site
      demonstrate how this protein can effect large changes in the size and shape of
      the substrate binding pocket to accommodate a diverse range of substrates.
      Finally, the previously identified BVMO signature sequence is highlighted for its
      role in coordinating domain movements. Taken together, these structures provide
      mechanistic insights into CHMO-catalyzed Baeyer-Villiger oxidation.

PMID- 19385645
TI  - The molecular face of prostate cancer.

PMID- 19385646
TI  - Preparation of functional aptamer films using layer-by-layer self-assembly.
AB  - Advances in many aptamer-based applications will require a better understanding
      of how an aptamer's molecular recognition ability is affected by its
      incorporation into a suitable matrix. In this study, we investigated whether a
      model aptamer system, the sulforhodamine B aptamer, would retain its binding
      ability while embedded in a multilayer polyelectrolyte film. Thin films
      consisting of poly(diallyldimethylammonium chloride) as the polycation and both
      poly(sodium 4-styrene-sulfonate) and the aptamer as the polyanions were deposited
      by the layer-by-layer approach and were compared to films prepared using calf
      thymus DNA or a random single-stranded oligonucleotide. Data from UV-vis
      spectroscopy, quartz crystal microbalance studies, confocal microscopy, and time
      of flight secondary ion mass spectrometry confirm that the aptamer's recognition
      of its target is retained, with no loss of specificity and only a modest
      reduction of binding affinity, while it is incorporated within the thin film.
      These findings open up a raft of new opportunities for the development and
      application of aptamer-based functional thin films.

PMID- 19385647
TI  - Electrophoretic behavior of copolymeric galacturonans including comments on the
      information content of the intermolecular charge distribution.
AB  - Capillary electrophoresis has been used to characterize samples of the
      copolymeric anionic polysaccharides homo- and rhamno-galacturonan (HG and RGI,
      respectively). In the case of HG, the ratios of the two component sugar residues,
      galacturonic acid and its methylesterified analogue, have been controlled
      chemically to produce samples comprised of varying degrees of
      methylesterification (DM). The mapping of the measured electrophoretic mobilities
      to the biopolymer charge density has been considered in some detail and for HG
      substrates with random intramolecular patterns of methylesterification it is
      shown that the experimentally extracted intermolecular DM distribution agrees
      well with the predictions of calculations based on the binomial theorem. This
      demonstrates that the intermolecular distribution of the methylesterification of
      pectin samples contains information on the intramolecular pattern by virtue of
      the fact that they are both manifestations of the same statistical process.

PMID- 19385648
TI  - Effect of confinement and kinetics on the morphology of phase separating gelatin
      maltodextrin droplets.
AB  - The effect of confinement on the structure evolution and final morphology during
      phase separation and gelation of gelatin and maltodextrin was investigated and
      compared to the structures seen in bulk phase. Emulsion droplets with diameters
      from 4 to 300 mum were analyzed using confocal laser scanning microscopy and
      image analysis. With the confocal laser scanning microscope it was possible to
      follow the entire phase separating process inside the droplets in real-time. The
      samples were either quenched directly from 70 degrees C down to 20 degrees C or
      exposed to holding times at 40 degrees C. Different cooling procedures were
      studied to examine the structure evolution both before and after gelation in the
      restricted geometries. The concentration of the biopolymer mixture was kept
      constant at 4 w/w% gelatin and 6 w/w% maltodextrin. The results revealed that the
      size of the confinement had a great effect on both the initiation of phase
      separation and the final morphology of the microstructure inside the emulsion
      droplets. The phase separation in small droplets was observed to occur at a
      temperature above the phase separating temperature for bulk. Small droplets had
      either a microstructure with a shell of maltodextrin and core of gelatin or a
      microstructure where the two biopolymers had formed two separate bicontinuous
      halves. The initiation of phase separation in large droplets was similar to what
      was seen in bulk. The microstructure in large droplets was discontinuous,
      resembling the morphology in bulk phase. The kinetics had an effect on the
      character of the maltodextrin inclusions, as the cooling procedure of a direct
      quench gave spherical inclusions with an even size distribution, while a holding
      time at 40 degrees C resulted in asymmetrical and elongated inclusions.

PMID- 19385649
TI  - Mixing a sol and a precipitate of block copolymers with different block ratios
      leads to an injectable hydrogel.
AB  - A facile method to obtain a thermoreversible physical hydrogel was found by
      simply mixing an aqueous sol of a block copolymer with a precipitate of a similar
      copolymer but with a different block ratio. Two ABA-type triblock copolymers
      poly(D,L-lactic acid-co-glycolic acid)-B-poly(ethylene glycol)-B-poly(D,L-lactic
      acid-co-glycolic acid) (PLGA-PEG-PLGA) were synthesized. One sample in water was
      a sol in a broad temperature region, while the other in water was just a
      precipitate. The mixture of these two samples with a certain mix ratio underwent,
      however, a sol-to-gel-to-precipitate transition upon an increase of temperature.
      A dramatic tuning of the sol-gel transition temperature was conveniently achieved
      by merely varying mix ratio, even in the case of a similar molecular weight. Our
      study indicates that the balance of hydrophobicity and hydrophilicity within this
      sort of amphiphilic copolymers is critical to the inverse thermal gelation in
      water resulting from aggregation of micelles. The availability of encapsulation
      and sustained release of lysozyme, a model protein by the thermogelling systems
      was confirmed. This "mix" method provides a very convenient approach to design
      injectable thermogelling biomaterials with a broad adjustable window, and the
      novel copolymer mixture platform is potentially used in drug delivery and other
      biomedical applications.

PMID- 19385650
TI  - A stochastic, local mode treatment of high-energy gas-liquid collisions.
AB  - The scattering angle distributions of high-energy molecular beams at the surfaces
      of three different liquids are treated in terms local mode theory. This is
      achieved by setting up a stochastic process modeling the effect of a
      superposition of local mode surface displacements on the incoming particle's
      trajectory. The results are found to be in good qualitative agreement with
      experiment, and directions for further work are indicated.

PMID- 19385651
TI  - Domain averaged Fermi hole analysis for open-shell systems.
AB  - The Article reports the extension of the new original methodology for the
      analysis and visualization of the bonding interactions, known as the analysis of
      domain averaged Fermi holes (DAFH), to open-shell systems. The proposed
      generalization is based on straightforward reformulation of the original approach
      within the framework of unrestricted Hartree-Fock (UHF) and/or Kohn-Sham (UKS)
      levels of the theory. The application of the new methodology is demonstrated on
      the detailed analysis of the picture of the bonding in several simple systems
      involving the doublet state of radical cation NH(3)((+)) and the triplet ground
      state of the O(2) molecule.

PMID- 19385652
TI  - The photochromism and fluorescence of diarylethenes with a imidazole bridge unit:
      a strategy for the design of turn-on fluorescent diarylethene system.
AB  - A class of diarylethenes with a imidazole bridge unit has been synthesized and
      shows photochromic properties with UV/vis light irradiation. It is found that
      electronic properties of substituent in the imidazole bridge unit have a great
      effect on both photochromism and fluorescence of diarylethenes because of
      intramolecular charge transfer. Both "turn-on" and "turn-off" fluorescent
      diarylethenes systems can be achieved by simple modification of molecular
      structure and electronic properties of substituent, which provides a strategy for
      the design of new fluorescent diarylethene systems to be used as switches.

PMID- 19385653
TI  - More sustainable approaches for the synthesis of N-based heterocycles.

PMID- 19385654
TI  - Iridium-catalyzed addition of acid chlorides to terminal alkynes.
AB  - An iridium N-heterocyclic carbene (NHC) complex, IrCl(cod)(IPr), successfully
      catalyzed an addition of common aromatic acid chlorides to terminal alkynes to
      afford (Z)-beta-chloro-alpha,beta-unsaturated ketones regio- and
      stereoselectively. When the NHC ligand (IPr) was changed to a phosphine (RuPhos),
      the addition occurred with decarbonylation to give the corresponding (Z)-vinyl
      chlorides. Furthermore, the former reaction using IrCl(cod)(IPr) can be applied
      to the catalytic synthesis of 2,5-disubstituted furans.

PMID- 19385655
TI  - Melamine detection in infant formula powder using near- and mid-infrared
      spectroscopy.
AB  - Near- and mid-infrared spectroscopy methods (NIR, FTIR-ATR, FTIR-DRIFT) were
      evaluated for the detection and quantification of melamine in infant formula
      powder. Partial least-squares (PLS) models were established for correlating
      spectral data to melamine concentration: R(2) > 0.99, RMSECV <= 0.9, and RPD >=
      12. Factorization analysis of spectra was able to differentiate unadulterated
      infant formula powder from samples containing 1 ppm melamine with no
      misclassifications, a confidence level of 99.99%, and selectivity > 2. These
      nondestructive methods require little or no sample preparation. The NIR method
      has an assay time of 1 min, and a 2 min total time to detection. The FTIR methods
      require up to 5 min for melamine detection. Therefore, NIR and FTIR methods
      enable rapid detection of 1 ppm melamine in infant formula powder.

PMID- 19385656
TI  - Resistance mechanism to bensulfuron-methyl in biotypes of Scirpus mucronatus L.
      collected in Chilean rice fields.
AB  - Two biotypes of Scirpus mucronatus not controlled with the herbicide bensulfuron
      methyl in rice fields were characterized by using field, greenhouse, and
      laboratory techniques. Seeds were collected in two rice areas [Parral (R1) and
      Linares (R2)], where bensulfuron-methyl at 150 g ha(-1) did not control S.
      mucronatus. A third seed sample of S. mucronatus susceptible (S) to bensulfuron
      methyl was collected in an area from Chile. The dose-response studies confirmed
      resistance to bensulfuron-methyl in R1 and R2 S. mucronatus biotypes; ratios
      (R/S) of the ED(50) values of resistant to susceptible plants were 1719 and 1627
      for R1 and R2, respectively. The biotype R1 also showed strong cross-resistance
      (ratios ranging from 1719 to 43) to sulfonylureas (bensulfuron-methyl,
      cyclosulfamuron, ethoxysulfuron, imazosulfuron, and pyrazosulfuron-ethyl) and
      imidazolinone (imazamox) and a weak cross-resistance (ratio of 1.705) to
      pyrimidinyloxybenzoates (bispyribac-sodium), all ALS inhibiting herbicides used
      in rice. Absorption, translocation, and metabolism results did not explain the
      differences in susceptibility among biotypes. The in vitro assays confirmed cross
      resistance to all ALS inhibitors tested and the level of cross resistance was
      bensulfuron-methyl > imazosulfuron ? cyclosulfamuron ? pyrazosulfuron-ethyl ?
      ethoxysulfuron > imazamox ? bispiribac-sodium. Molecular studies demonstrated
      that the Pro197His amino acid substitution on the ALS enzyme could explain the
      loss of affinity for the ALS-inhibiting herbicides.

PMID- 19385657
TI  - Filamentous polymer nanocarriers of tunable stiffness that encapsulate the
      therapeutic enzyme catalase.
AB  - Therapeutic proteins are prone to inactivation by aggregation, proteases and
      natural inhibitors, motivating development of protective delivery systems. Here
      we focus on protective encapsulation of the potent antioxidant enzyme, catalase,
      by filamentous polymer nanocarriers (f-PNC), with the specific goal of addressing
      whether polymer molecular weight (MW) controls formation and structural
      properties such as size and stiffness. While maintaining the same MW ratio of
      polyethylene glycol to polylactic acid, a series of PEG-b-PLA diblock copolymers
      were synthesized, with total MW ranging from about 10 kg/mol to 100 kg/mol. All
      diblocks formed f-PNC upon processing, which encapsulated active enzyme that
      proved resistant to protease degradation. Further, f-PNC stiffness, length, and
      thickness increased with increasing MW. Interestingly, heating above a polymer's
      glass transition temperature (<30 degrees C) increased f-PNC flexibility. Thus,
      we report here for the first time f-PNC that encapsulate an active enzyme with
      polymer MW-tunable flexibility, offering several potential therapeutic
      applications.

PMID- 19385658
TI  - Fibrin-lipoplex system for controlled topical delivery of multiple genes.
AB  - Nonviral gene delivery via natural biomacromolecules show great promise as
      controlled release systems while avoiding the associated drawbacks with viral
      gene delivery such as immunogenicity and safety issues. Here, a fibrin-lipoplex
      system for topical delivery of multiple genes is described. In vitro release
      analysis showed efficient retention of the lipoplexes in the fibrin scaffold. The
      biomolecular interaction between fibrinogen and liposomes was investigated
      qualitatively using surface plasmon resonance. The strong binding between the
      lipoplexes and the fibrinogen component of the scaffold was observed and that
      could explain the in vitro release profile observed in our studies. Both in vitro
      and in vivo transfection studies using multiple reporter genes were performed to
      establish the bioactivity of released lipoplexes. The ability of the lipoplexes
      to transfect fibroblasts in vitro was shown to be maintained even after extended
      periods of encapsulation within the scaffold. Furthermore, in a rabbit ear ulcer
      model, the fibrin-lipoplex system was shown to have significantly higher
      transfection efficiency for two reporter genes at day 7 when compared to
      lipoplexes alone, suggesting that this fibrin-lipoplex system is suitable for
      extended release of lipoplexes for topical gene delivery applications.

PMID- 19385659
TI  - Simple approach to stabilized micelles employing miktoarm terpolymers and
      stereocomplexes with application in paclitaxel delivery.
AB  - A simple and versatile approach to miktoarm co- and terpolymers from carbonate
      functional oligomers is described. The key building block employed is a
      carboxylic acid functional cyclic carbonate, derived from 2,2
      bis(methylol)propionic acid, that was readily coupled to a hydroxyl functional
      monomethylether poly(ethylene glycol) oligomer. Ring-opening of the cyclic
      carbonate using functional amines generates a carbamate linkage bearing a
      functional group capable of initiating either controlled radical or ring-opening
      polymerization, together with a primary hydroxyl group for ring-opening
      polymerization. Two tandem polymerization steps were possible which add the
      second two arms, thus generating the targeted ABC miktoarm terpolymer. The
      resulting amphiphilic miktoarm terpolymers containing poly(D- and L-lactide)
      formed polylactide stereocomplexes in the bulk. In aqueous solution, the
      stereocomplex mixture of Y-shaped miktoarm copolymers, poly(ethylene glycol)
      poly(D-lactide)-poly(D-lactide) and poly(ethylene glycol)-poly(L-lactide)-poly(L
      lactide), or the stereoblock miktoarm poly(ethylene glycol)-poly(D-lactide)
      poly(L-lactide) form stabilized micelles with a significantly lower critical
      micelle concentration than those derived from conventional stereo regular linear
      or Y-shaped amphiphiles. This simple and versatile approach provides a useful
      synthetic route to complex macromolecular architectures that can assemble into
      stable micelles. These micelles provide high capacity for loading of the
      anticancer drug paclitaxel and possess narrow size distribution as well as unique
      structure, leading to sustained and near zero-ordered release of drug without
      significant initial burst.

PMID- 19385660
TI  - Carrageenan-based hydrogels for the controlled delivery of PDGF-BB in bone tissue
      engineering applications.
AB  - One of the major drawbacks found in most bone tissue engineering approaches
      developed so far consists in the lack of strategies to promote vascularisation.
      Some studies have addressed different issues that may enhance vascularisation in
      tissue engineered constructs, most of them involving the use of growth factors
      (GFs) that are involved in the restitution of the vascularity in a damaged zone.
      The use of sustained delivery systems might also play an important role in the re
      establishment of angiogenesis. In this study, kappa-carrageenan, a naturally
      occurring polymer, was used to develop hydrogel beads with the ability to
      incorporate GFs with the purpose of establishing an effective angiogenesis
      mechanism. Some processing parameters were studied and their influence on the
      final bead properties was evaluated. Platelet derived growth factor (PDGF-BB) was
      selected as the angiogenic factor to incorporate in the developed beads, and the
      results demonstrate the achievement of an efficient encapsulation and controlled
      release profile matching those usually required for the development of a fully
      functional vascular network. In general, the obtained results demonstrate the
      potential of these systems for bone tissue engineering applications.

PMID- 19385661
TI  - Plasmon near-field coupling in metal dimers as a step toward single-molecule
      sensing.
AB  - In this study, we report on ultrasensitive protein detection with
      lithographically prepared plasmonic nanostructures. We have engineered optical
      nanosensors by the combined approach of negative resist, electron beam
      lithography, and reactive ion etching to form highly reproducible arrays of gold
      dimers in which the near-field coupling in their subwavelength gap enables for
      scaling the sensing volume down to the single-protein scale. In good agreement
      with recent theoretical predictions, the dimer geometry offers enhanced
      sensitivity compared to isolated particles for the detection of both small
      organic molecules and proteins. Beyond, by exploiting size exclusion, we are
      capable of monitoring the number of proteins able to bind across the gap region
      through the precise engineering of the structures coupled to the selective
      binding of a surface-assembled monolayer and covalent attachment of the protein.

PMID- 19385662
TI  - Zn/InCl(3)-mediated pinacol cross-coupling reactions of aldehydes with alpha,beta
      unsaturated ketones in aqueous media.
AB  - A zinc/indium chloride-mediated pinacol cross-coupling reaction between aldehyde
      and alpha,beta-unsaturated ketone in aqueous media was developed. The 1,2-diols
      were obtained in moderate to good yields with up to 93:7 diastereoselectivity.

PMID- 19385663
TI  - Capillary electrophoresis of conidia from cultivated microscopic filamentous
      fungi.
AB  - In immunocompromised people fungal agents are able to cause serious infections
      with high mortality rate. An early diagnosis can increase the chances of survival
      of the affected patients. Simultaneously, the fungi produce toxins and they are
      frequent cause of allergy. Currently, various methods are used for detection and
      identification of these pathogens. They use microscopic examination and growth
      characteristic of the fungi. New methods are based on the analysis of structural
      elements of the target microorganisms such as proteins, polysaccharides,
      glycoproteins, nucleic acids, etc. for the construction of antibodies, probes,
      and primers for detection. The above-mentioned methods are time-consuming and
      elaborate. Here hydrophobic conidia from the cultures of different strains of the
      filamentous fungi were focused and separated by capillary zone electrophoresis
      and capillary isoelectric focusing. The detection was optimized by dynamic
      modifying of conidia by the nonionogenic tenside on the basis of pyrenebutanoate.
      Down to 10 labeled conidia of the fungal strains were fluorometrically detected,
      and isoelectric points of conidia were determined. The observed isoelectric
      points were compared with those obtained from the separation of the cultured
      clinical samples, and they were found to be not host-specific.

PMID- 19385664
TI  - Structures of Abeta-related peptide--monoclonal antibody complexes.
AB  - Passive immunotherapy (PI) is being explored as a potential therapeutic against
      Alzheimer's disease. The most promising antibodies (Abs) used in PI target the
      EFRH motif of the Abeta N-terminus. The monoclonal anti-Abeta Ab PFA1 recognizes
      the EFRH epitope of Abeta. PFA1 has a high affinity for Abeta fibrils and
      protofibrils (0.1 nM), as well as good affinity for Abeta monomers (20 nM).
      However, PFA1 binds the toxic N-terminally modified pyroglutamate peptide pyro
      Glu3-Abeta with a 77-fold loss in affinity compared to the WT Abeta(1-8).
      Furthermore, our earlier work illustrated PFA1's potential for cross-reactivity.
      The receptor tyrosine kinase Ror2, which plays a role in skeletal and bone
      formation, possesses the EFRH sequence. PFA1 Fab binds the Ror2(518-525) peptide
      sequence REEFRHEA with a 3-fold enhancement over WT Abeta(1-8). In this work, the
      crystal structures of the hybridoma-derived PFA1 Fab in complex with pyro-Glu3
      Abeta peptide and with a cross-reacting peptide from Ror2 have been determined at
      resolutions of 1.95 and 2.7 A, respectively. As with wild-type Abeta, these
      peptides bind to the Fab via a combination of charge- and shape-complementarity,
      hydrogen-bonding, and hydrophobic interactions. Comparison of the structures of
      the four peptides Abeta(1-8), Grip1, pyro-Glu3-Abeta(3-8), and Ror2 in complex
      with PFA1 shows that the greatest conformational flexibility occurs at residues 2
      to 3 and 8 of the peptide. These structures provide a molecular basis of the
      specificity tolerance of PFA1 and its ability to recognize Abeta N-terminal
      heterogeneity. The structures provide clues to improving mAb specificity and
      affinity for pyroglutamate Abeta.

PMID- 19385665
TI  - Activation of anthranilate phosphoribosyltransferase from Sulfolobus solfataricus
      by removal of magnesium inhibition and acceleration of product release .
AB  - Anthranilate phosphoribosyltransferase from the hyperthermophilic archaeon
      Sulfolobus solfataricus (ssAnPRT) is encoded by the sstrpD gene and catalyzes the
      reaction of anthranilate (AA) with a complex of Mg(2+) and 5'-phosphoribosyl
      alpha1-pyrophosphate (Mg.PRPP) to N-(5'-phosphoribosyl)-anthranilate (PRA) and
      pyrophosphate (PP(i)) within tryptophan biosynthesis. The ssAnPRT enzyme is
      highly thermostable (half-life at 85 degrees C = 35 min) but only marginally
      active at ambient temperatures (turnover number at 37 degrees C = 0.33 s(-1)). To
      understand the reason for the poor catalytic proficiency of ssAnPRT, we have
      isolated from an sstrpD library the activated ssAnPRT-D83G + F149S double mutant
      by metabolic complementation of an auxotrophic Escherichia coli strain. Whereas
      the activity of purified wild-type ssAnPRT is strongly reduced in the presence of
      high concentrations of Mg(2+) ions, this inhibition is no longer observed in the
      double mutant and the ssAnPRT-D83G single mutant. The comparison of the crystal
      structures of activated and wild-type ssAnPRT shows that the D83G mutation alters
      the binding mode of the substrate Mg.PRPP. Analysis of PRPP and Mg(2+)-dependent
      enzymatic activity indicates that this leads to a decreased affinity for a second
      Mg(2+) ion and thus reduces the concentration of enzymes with the inhibitory
      Mg(2).PRPP complex bound to the active site. Moreover, the turnover number of the
      double mutant ssAnPRT-D83G + F149S is elevated 40-fold compared to the wild-type
      enzyme, which can be attributed to an accelerated release of the product PRA.
      This effect appears to be mainly caused by an increased conformational
      flexibility induced by the F149S mutation, a hypothesis which is supported by the
      reduced thermal stability of the ssAnPRT-F149S single mutant.

PMID- 19385668
TI  - Engineered nanoscaled polyplex gene delivery systems.
AB  - Improving the transfection efficiencies of nonviral gene delivery requires
      properly engineered nanoscaled delivery carriers that can overcome the multiple
      barriers associated with the delivery of oligonucleotides from the site of
      administration to the nucleus or cytoplasm of the target cell. This article
      reviews the current advantages and limitation of polyplex nonviral delivery
      systems, including the apparent barriers that limit gene expression efficiency
      compared to physical methods such as hydrodynamic dosing and electroporation. An
      emphasis is placed on engineered nanoscaled polyplexes (NSPs) of modular design
      that both self-assemble and systematically disassemble at the desired stage of
      delivery. It is suggested that NSPs of increasingly sophisticated designs are
      necessary to improve the efficiency of the rate limiting steps in gene delivery.

PMID- 19385666
TI  - Myelin basic protein binds to and inhibits the fibrillar assembly of Abeta42 in
      vitro.
AB  - The deposition of amyloid beta-protein (Abeta) fibrils into plaques within the
      brain parenchyma and along cerebral blood vessels is a hallmark of Alzheimer's
      disease. Abeta peptides are produced through the successive cleavage of the Abeta
      precursor protein by beta- and gamma-secretase, producing peptides between 39 and
      43 amino acids in length. The most common of these are Abeta40 (the most
      abundant) and Abeta42. Abeta42 is more fibrillogenic than Abeta40 and has been
      implicated in early Abeta plaque deposition. Our previous studies determined that
      myelin basic protein (MBP) was capable of inhibiting fibril formation of a highly
      fibrillogenic Abeta peptide containing both E22Q (Dutch) and D23N (Iowa)
      mutations associated with familial forms of cerebral amyloid angiopathy [Hoos, M.
      D., et al. (2007) J. Biol. Chem. 282, 9952-9961]. In this study, we show through
      a combination of biochemical and ultrastructural techniques that MBP is also
      capable of inhibiting the beta-sheet fibrillar assembly of the normal Abeta42
      peptide. These findings suggest that MBP may play a role in regulating the
      deposition of Abeta42 and thereby also may regulate the early formation of
      amyloid plaques in Alzheimer's disease.

PMID- 19385669
TI  - Inter- and intramolecular photochemical reactions of fleroxacin.
AB  - In the cation formed by photoinduced C-F bond cleavage in fleroxacin,
      intramolecular reaction with the N-ethyl chain is prevented by the electron
      withdrawing effect of fluorine and intermolecular attack by nucleophiles is
      facilitated.

PMID- 19385670
TI  - Convenient synthesis of tetra- and hexaarylanthracenes by means of
      RuH2(CO)(PPh3)3-catalyzed C-H arylation of anthraquinone with arylboronates.
AB  - A new method for the synthesis of multiarylanthracenes was developed by means of
      the RuH(2)(CO)(PPh(3))(3)-catalyzed arylation of anthraquinone with
      arylboronates. This method consists of short and straightforward sequences
      starting with an easily accessible anthraquinone and is applicable to the
      syntheses of various multiarylanthracenes including those bearing twisted
      backbones.

PMID- 19385671
TI  - The aignopsanes, a new class of sesquiterpenes from selected chemotypes of the
      sponge Cacospongia mycofijiensis.
AB  - A survey of individual specimens of northern Papua New Guinea derived Cacospongia
      mycofijiensis has yielded novel sesquiterpenes, aignopsanoic acid A (1), methyl
      aignopsanoate A (2), and isoaignopsanoic acid A (3). The structures and absolute
      configurations of 1-3 were established using NMR data, X-ray crystallography
      results, and an analysis of CD properties. Two of these metabolites, 1 and 2,
      were moderately active against Trypanosoma brucei, the parasite responsible for
      sleeping sickness.

PMID- 19385672
TI  - Enantioselective synthesis of Janus kinase inhibitor INCB018424 via an
      organocatalytic aza-Michael reaction.
AB  - An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza
      Michael addition of pyrazoles (16 or 20) to (E)-3-cyclopentylacrylaldehyde (23)
      using diarylprolinol silyl ether as the catalyst was developed. Michael adducts
      (R)-24 and (R)-27 were isolated in good yield and high ee and were readily
      converted to INCB018424.

PMID- 19385674
TI  - Ion-pair dissociation dynamics of HCl: fast predissociation.
AB  - We have studied the ion-pair dissociation dynamics of HCl --> Cl(-) ((1)S(0)) +
      H(+) in the 14.41-14.60 eV using tunable XUV laser and the velocity map imaging
      method. The measured ion-pair yield spectrum has P- and R-branch resolved
      vibrational structure, which indicates a predissociation mechanism for the ion
      pair dissociation. All of the anisotropy parameters for the angular distribution
      of the fragments have the limiting values of beta = 2, which suggests that the
      predissociation occurs via (1)Sigma(+) Rydberg states, and is fast in comparison
      with the rotational period of HCl. To understand the predissociation dynamics,
      the diabatic potential energy curve of the ion-pair state has been calculated at
      the MRCI/CAS/vtz level. The experimental and theoretical results obtained in this
      work have provided a solid foundation for the previously proposed mechanism that
      the ion-pair dissociation occurs via predissociation of Rydberg states converging
      to HCl(+) (A(2)Sigma(+)).

PMID- 19385675
TI  - Dynamics of OH formation in the photodissociation of o-nitrobenzoic acid at 295
      and 355 nm.
AB  - Photodissociation dynamics of o-nitrobenzoic acid at 295 and 355 nm is studied by
      probing the nascent OH photoproduct employing the single-photon laser-induced
      fluorescence technique. At both of the photolysis wavelengths, the OH fragments
      are found to be vibrationally cold but have different rotational state
      distributions. Upon photolysis at 295 nm, the relative population of OH in
      different rotational states does not follow the Boltzmann equilibrium
      distribution, whereas upon photolysis at 355 nm, a Boltzmann distribution is
      observed with a rotational temperature of 1010 +/- 100 K. Between the two spin
      orbit states, (2)Pi(3/2) and (2)Pi(1/2), the former is found to be preferentially
      populated, and the distribution of the Pi(A') state for the Lambda-doublet is
      dominant at both of the wavelengths studied. Several possible dissociation
      pathways of o-nitrobenzoic acid leading to formation of the OH fragment are
      investigated computationally. On the basis of the theoretical and experimental
      studies, a possible mechanism of OH formation from the photodissociation of o
      nitrobenzoic acid at 295 and 355 nm is proposed.

PMID- 19385676
TI  - EPR line shifts and line shape changes due to spin exchange of nitroxide free
      radicals in liquids: 6. Separating line broadening due to spin exchange and
      dipolar interactions.
AB  - EPR spectra of perdeuterated 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (PDT) are
      studied as functions of molar concentration, c, and temperature, T, in water and
      70 wt % glycerol in water. The increase of the intrinsic line width averaged over
      the three hyperfine lines, B(tot), varies linearly with c with zero intercept in
      both solvents at all temperatures; therefore dB(tot)/dc is independent of c. The
      spin exchange induced dispersion, from which the spin exchange frequency,
      omega(e), may be computed, increases linearly with B(tot), passing through the
      origin in water and in 70% glycerol at high temperatures; however, at low
      temperatures, where dipolar interactions broaden the spectra, linearity does not
      prevail until B(tot) > 1 G due to a contribution of dipolar interactions to the
      dispersion. The broadening constant due to spin exchange, dB(e)/dc, is found from
      the slope of the linear region, permitting a computation of the dipolar constant,
      dB(dip)/dc = dB(tot)/dc - dB(e)/dc. Thus, the separation of concentration
      broadening into spin exchange and dipolar contributions is effected without
      having to appeal to some supposed temperature dependence of the two interactions.
      The fractional broadening by spin exchange, Omega(T), is near unity at high
      temperatures in both solvents, decreasing to zero in 70% glycerol at 273 K.
      Omega(T) is a continuous function of the inverse rotational correlation time of
      PDT but is discontinuous as a function of T/eta where eta is the shear viscosity.
      Omega(T) = 0.5, where spin exchange and dipolar interactions contribute equally
      to the line width occurs at T/eta = 20 +/- 1 K/cP in 70% glycerol. Hydrodynamic
      predictions of dB(e)/dc via the Stokes-Einstein (SE) equation are remarkably
      accurate in 70% glycerol comparable with the results in a series of alkanes. In
      water, dB(e)/dc is linear with T/eta with zero intercept as required by the SE;
      however, with slope a factor of 0.73 smaller. dB(dip)/dc is reasonably predicted
      by the SE only at very small values of eta/T very quickly following an
      approximately logarithmic dependence rather that the linear prediction. Values of
      dB(dip)/dc approach a plateau above eta/T = 0.20 cP/K that is about one-half the
      solid state limit. Line shifts due to spin exchange are not yet useful to deduce
      values of Omega(T) due to a lack of knowledge of the time between re-encounters;
      however, they may be used to verify the values determined from line broadening
      and spin exchange induced dispersion. Some effects at low temperatures in 70%
      glycerol suggest that the effects of dipolar interaction are inadequately
      described by the widely accepted theory.

PMID- 19385677
TI  - Adiabatic interaction leading to the avoided crossing between the twin
      3(1)Delta(g) and 4(1)Delta(g) Rydberg States in Na2.
AB  - We present detailed investigations of our previously reported observations of the
      3(1)Delta(g) and 4(1)Delta(g) Rydberg states having separated-atom limits of
      Na(3s) + Na(4d) and Na(3s) + Na(4f), respectively, of Na(2) using high-resolution
      cw optical-optical double resonance spectroscopic measurements and analyzing the
      assigned rovibrational energy levels both by the individual linear fit method and
      the Dunham polynomial fit method. We have sorted out e/f-parity observed energy
      levels, and then from the Dunham polynomial fits of the e-parity levels, we have
      derived molecular constants and constructed Rydberg-Klein-Rees potentials of the
      3(1)Delta(g) and 4(1)Delta(g) states, which appear to be twin states with an
      avoided crossing at R(c) = 4.10 A and a splitting of DeltaE(c) = 94 cm(-1). The
      potentials are in good agreement with the ab initio calculations and linear fit
      results. The Lambda-doubling splittings and the (f-d) l-mixing are investigated.
      A detailed discussion is focused on the adiabatic interaction of the perturbed
      molecular wave functions/states causing mutual amplitude/intensity sharing giving
      rise to avoided crossing between the 3(1)Delta(g) and 4(1)Delta(g) states.

PMID- 19385678
TI  - Matrix isolation infrared spectrum of the sulfuric acid-monohydrate complex: new
      assignments and resolution of the "missing H-Bonded v(OH) band" issue.
AB  - The matrix isolation infrared spectra of "dry" and "wet" vapors of sulfuric acid
      have been investigated as trapped in solid argon matrices. The availability of a
      spectrum of trapped anhydrous acid vapor and its comparison with the spectra of
      trapped water containing vapors of the acid allowed the identification of the
      hydrogen-bonding shifted hydroxyl bands for both the acid and the water moieties
      of the monohydrated H(2)SO(4).H(2)O complex. The experimental results are
      compared to the various theoretically calculated wavenumber values of the acid
      and its monohydrated complex. The complex stabilization energies, as obtained
      from calculations and empirical correlations, are compared.

PMID- 19385679
TI  - Kinetics of ion-molecule reactions with dimethyl methylphosphonate at 298 K for
      chemical ionization mass spectrometry detection of GX.
AB  - Kinetics studies of a variety of positive and negative ions reacting with the GX
      surrogate, dimethyl methylphosphonate (DMMP), were performed. All protonated
      species reacted rapidly, that is, at the collision limit. The protonated reactant
      ions created from neutrals with proton affinities (PAs) less than or equal to the
      PA for ammonia reacted exclusively by nondissociative proton transfer. Hydrated
      H(3)O(+) ions also reacted rapidly by proton transfer, with 25% of the products
      from the second hydrate, H(3)O(+)(H(2)O)(2), forming the hydrated form of
      protonated DMMP. Both methylamine and triethylamine reacted exclusively by
      clustering. NO(+) also clustered with DMMP at about 70% of the collision rate
      constant. O(+) and O(2)(+) formed a variety of products in reactions with DMMP,
      with O(2)(+) forming the nondissociative charge transfer product about 50% of the
      time. On the other hand, many negative ions were less reactive, particularly,
      SF(5)(-), SF(6)(-), CO(3)(-), and NO(3)(-). However, F(-), O(-), and O(2)(-) all
      reacted rapidly to generate m/z = 109 amu anions (PO(3)C(2)H(6)(-)). In addition,
      product ions with m/z = 122 amu from H(2)(+) loss to form H(2)O were the dominant
      ions produced in the O(-) reaction. NO(2)(-) underwent a slow association
      reaction with DMMP at 0.4 Torr. G3(MP2) calculations of the ion energetics
      properties of DMMP, sarin, and soman were also performed. The calculated
      ionization potentials, proton affinities, and fluoride affinities were consistent
      with the trends in the measured kinetics and product ion branching ratios. The
      experimental results coupled with the calculated ion energetics helped to predict
      which ion chemistry would be most useful for trace detection of the actual
      chemical agents.

PMID- 19385681
TI  - Why oxonium cation in the crystal phase is a bad acceptor of hydrogen bonds: a
      charge density analysis of potassium oxonium bis(hydrogensulfate).
AB  - Peculiarities of chemical bonding in the crystal of potassium oxonium
      bis(hydrogensulfate) were analyzed by means of R. Bader's "Atoms in Molecule"
      theory on the basis of the experimental data. The results obtained were shown to
      provide insight into the tendency of the oxygen atom of the oxonium moiety to
      avoid the H-bond formation in its crystalline salts.

PMID- 19385680
TI  - Reactive uptake of N2O5 by aerosols containing dicarboxylic acids. Effect of
      particle phase, composition, and nitrate content.
AB  - Reactive uptake coefficients for loss of N(2)O(5) to micron-size aerosols
      containing oxalic malonic, succinic, and glutaric acids, and mixtures with
      ammonium hydrogen sulfate and ammonium sulfate, are presented. The uptake
      measurements were made using two different systems: atmospheric pressure laminar
      flow tube reactor (Cambridge) and the Large Indoor Aerosol Chamber at
      Forschungszentrum Juelich. Generally good agreement is observed for the data
      recorded using the two techniques. Measured uptake coefficients lie in the range
      5 x 10(-4)-3 x 10(-2), dependent on relative humidity, on particle phase, and on
      particle composition. Uptake to solid particles is generally slow, with observed
      uptake coefficients less than 1 x 10(-3), while uptake to liquid particles is
      around an order of magnitude more efficient. These results are rationalized using
      a numerical model employing explicit treatment of both transport and chemistry.
      Our results indicate a modest effect of the dicarboxylic acids on uptake and
      confirm the strong effect of particle phase, liquid water content, and
      particulate nitrate concentrations.

PMID- 19385682
TI  - The probable molecular association in liquid D-1-propanol through neutron
      diffraction.
AB  - The neutron scattering data of liquid D-1-propanol at room temperature has been
      carefully analyzed to extract the probable molecular association. The molecular
      conformation (quite elongated) being very different from its isomer 2-propanol
      (somewhat spherical) would suggest a different type of molecular association in 1
      propanol. The probable molecular associations like open chain trimer (as in
      recent X-ray work) to pentamer (winding) as in earlier X-ray analysis in addition
      to hexameric ring clusters (as reported in 2-propanol and other alcohols) are
      compared. It is surprisingly seen that hexameric rings are most probable
      molecular association in 1-propanol too.

PMID- 19385683
TI  - Eta3-sandwich-like complexes based on the smallest polynitrogen ring.
AB  - Over the past decades, polynitrogen chemistry has witnessed rapidly growing
      progress. Unfortunately and to our great surprise, eta(3)-assembled species based
      on the simplest polynitrogen ring (N(3)) have never been reported. In this paper,
      we report the first successful assembly design of the long-escaped N(3)-based
      compounds, that is, [N(3)NiN(3)](2-), [N(3)M(CO)(2)N(3)](q) ((M,q), = (Fe,0) (Mn,
      1)), [N(3)M(CO)(3)](q) ((M,q) = (Co,0), (Fe,-1)), and [N(3)MCp](q) ((M,q) = (Ni,
      0), (Co,-1)), at the density functional level. The conversion and dissociation of
      them need to overcome considerable barriers kinetically. To our surprise, the
      detailed structural, charge distribution, and orbital analyses consistently
      reveal a triplet polynitrogen unit, cyclic-(3)N(3)(-), rather than another
      simplest trinitrogen unit cyclic-(1)N(3)(+). The two unpaired spins within the
      naked cyclic-(3)N(3)(-) have effectively participated in the bonding interaction
      with the central transition-metal atoms (here, M is Ni, Fe, Co, and Mn).
      Moreover, the possible experimental routes of N(3)Co(CO)(3) were proposed. The
      diradical-like polynitrogen ring, cyclic-(3)N(3)(-), would add to the
      polynitrogen family as a novel building block. The assembly-designed species
      await future experimental verification.

PMID- 19385684
TI  - Information-theoretical analysis of time-correlated single-photon counting
      measurements of single molecules.
AB  - Time-correlated single photon counting allows luminescence lifetime information
      to be determined on a single molecule level. This paper develops a formalism to
      allow information theory analysis of the ability of luminescence lifetime
      measurements to resolve states in a single molecule. It analyzes the information
      content of the photon stream and the fraction of that information that is
      relevant to the state determination problem. Experimental losses of information
      due to instrument response, digitization, and different types of background are
      calculated and a procedure to determine the optimal value of experimental
      parameters is demonstrated. This paper shows how to use the information
      theoretical formalism to evaluate the number of photons required to distinguish
      dyes that differ only by lifetime. It extends this idea to include distinguishing
      molecular states that differ in the electron transfer quenching or resonant
      energy transfer and shows how the differences between the lifetime of signal and
      background can help distinguish the dye position in an excitation beam.

PMID- 19385685
TI  - Comment on "closing the loop on bond selective chemistry using tailored strong
      field laser pulses".

PMID- 19385687
TI  - Improvements to the percolator algorithm for Peptide identification from shotgun
      proteomics data sets.
AB  - Shotgun proteomics coupled with database search software allows the
      identification of a large number of peptides in a single experiment. However,
      some existing search algorithms, such as SEQUEST, use score functions that are
      designed primarily to identify the best peptide for a given spectrum.
      Consequently, when comparing identifications across spectra, the SEQUEST score
      function Xcorr fails to discriminate accurately between correct and incorrect
      peptide identifications. Several machine learning methods have been proposed to
      address the resulting classification task of distinguishing between correct and
      incorrect peptide-spectrum matches (PSMs). A recent example is Percolator, which
      uses semisupervised learning and a decoy database search strategy to learn to
      distinguish between correct and incorrect PSMs identified by a database search
      algorithm. The current work describes three improvements to Percolator. (1)
      Percolator's heuristic optimization is replaced with a clear objective function,
      with intuitive reasons behind its choice. (2) Tractable nonlinear models are used
      instead of linear models, leading to improved accuracy over the original
      Percolator. (3) A method, Q-ranker, for directly optimizing the number of
      identified spectra at a specified q value is proposed, which achieves further
      gains.

PMID- 19385688
TI  - Large aggregated ions found in some protic ionic liquids.
AB  - Large aggregated parent ions, for example, C(8)A(7)(+) (C = cation and A =
      anion), have been observed within some protic ionic liquids (PILs) using
      electrospray ionization mass spectrometry (ESI-MS). We have shown that the
      formation and size of aggregates is dependent on the nature of the anion and
      cation. Solvent structuring in select PILs through aggregation can contribute to
      their classification as "poor ionic liquids" and can also strongly influence the
      entropic component to the free energy of amphiphile self-assembly in select PILs.

PMID- 19385689
TI  - Computing ion solvation free energies using the dipolar Poisson model.
AB  - A new continuum model is presented for computing the solvation free energies of
      cations in water. It combines in a single formalism based on statistical
      thermodynamics the Poisson model for electrostatics with the Langevin dipole
      model to account for nonuniform water dipole distribution around the ions. An
      excellent match between experimental and computed solvation free energies is
      obtained for 10 monovalent and divalent ions.

PMID- 19385690
TI  - The properties of water: insights from quantum simulations.
AB  - The properties of water play a central role in many phenomena of relevance to
      different areas of science, including physics, chemistry, biology, geology, and
      climate research. Although well studied for decades, the behavior of water under
      different conditions and in different environments still remains mysterious and
      often surprising. In this article, various efforts aimed at providing a
      comprehensive representation of the water properties at a molecular level through
      computer modeling and simulation will be described. In particular, the unique
      role played by the hydrogen-bond network will be examined, first in liquid water,
      then in the solvation of model biological compounds, and finally in ice,
      especially highlighting the important effects related to the quantization of the
      nuclear motion.

PMID- 19385691
TI  - Mechanistic insight by in situ FTIR for the gas phase photo-oxidation of ethylene
      by V-doped titania and nano titania.
AB  - Vanadium-doped titania is found to be a better photocatalyst for gas phase photo
      oxidation of ethylene than nano titania. In situ FTIR studies were undertaken to
      elucidate the mechanistic pathway for ethylene oxidation on these two catalyst
      surfaces. Vanadium doping leads to formation of more chemisorbed hydroxyl
      species, which makes it a better photocatalyst. The labile hydroxyls which were
      responsible for the reduction of V(5+) to V(4+) during the process of calcination
      were also ascertained. The ethylene decomposition occurs via formation of ethoxy
      groups, transformed to acetaldehyde or enolates, subsequently to
      acetates/formates, and then to CO(2). The enolates were more stabilized on the
      TiO(2) surface, leading to formation of formates along with the acetates. On
      vanadium-doped TiO(2), acetaldehyde was more stabilized than its enol tautomer,
      leading to the formation of labile acetic acid and acetates. The formation of the
      labile acetic acid, adsorbed acetates, and the adsorbed acetate -M salts led to
      easier oxidation of them to provide higher yield of CO(2). The higher positive
      charge density over Ti in Ti(0.95)V(0.05)O(2) with respect to nano TiO(2) makes
      the acetate (stronger nucleophile) a more stable intermediate on it.

PMID- 19385692
TI  - Monitoring and interpretation of photoinduced biochemical processes by rapid-scan
      FTIR difference spectroscopy and hybrid hard and soft modeling.
AB  - Natural photochemical processes often require special instrumentation to monitor
      them at a suitable time scale. Rapid-scan FTIR difference spectroscopy is one of
      the preferred techniques to obtain rich structural information in the scale of
      milliseconds about photochemical processes of complex natural systems. The
      difference spectra obtained by this technique enhance the fine spectroscopic
      changes undergone during the process but require powerful data analysis
      methodologies to take full advantage of the information provided. Hybrid hard-
      and soft-modeling methodologies allow for coping with difficulties linked to the
      nature of the time-resolved measurement and to the complexity of the kinetic
      model describing the natural photochemical process. Thus, this methodology
      presents the following advantages: (a) handles difference spectra, taking into
      account the consequences of the lack of measurement about the initial stage of
      the process, (b) models events of the process that may be defined by a kinetic
      model (by hard modeling) and events that do not obey a mechanistic behavior (by
      soft modeling), (c) adapts to the photoaccumulation/relaxation stages of
      reversible photochemical processes, and (d) works simultaneously with series of
      experiments performed in different conditions and showing different kinetic
      behavior. The results of this data treatment provide complete kinetic information
      on the photochemical processes, e.g., rate constants, and a global picture of the
      difference spectra and the concentration profiles linked to each of the events
      (hard or soft modeled) contributing to the measured signal. The performance of
      the combination of time-resolved differential FTIR and hybrid hard and soft
      modeling is shown in a complex case study related to the photosynthetic activity
      of the reaction center of the purple bacteria Rhodobacter sphaeroides.

PMID- 19385693
TI  - Energy landscapes associated with the self-aggregation of an alanine-based
      oligopeptide (AAKA)4.
AB  - The alanine-based 16-mer peptide (AAKA)(4) has recently been shown to aggregate
      into a hydrogel at centimolar concentrations and high ionic strength ( Measey, T.
      J.; Schweitzer-Stenner, R. J. Am. Chem. Soc. 2006 , 128 , 13324. ). This is a
      surprising result since the current understanding of peptide self-aggregation
      would lead one to expect that the positively charged lysine residues inhibit the
      formation of beta-sheet structures. The present study was aimed at shedding some
      light on the mechanism governing the initial phase of the self-aggregation
      process. To this end we measured CD and FTIR spectra of the (AAKA)(n) at
      millimolar concentration and low ionic strength and found that the peptide forms
      soluble aggregates rather than a hydrogel under these conditions. To analyze the
      initial phase of this aggregation process, we carried out simulations on the
      dimerization and trimerization of (AAKA)(4) using replica exchange molecular
      dynamics (MD) methods based on an implicit solvent model. The results indicate
      that the peptide aggregates into stable antiparallel beta-sheet structures under
      conditions comparable to experiments. Furthermore, the existence of trimers is a
      very sensitive function of the peptide concentration and temperature; no
      significant amount of trimers is formed at low concentration and the trimer
      population drops sharply as temperature increases above about 320 K. These
      results on oligomers are consistent with the trend observed in our experiments
      (reported elsewhere). We have also obtained the free energy landscapes of the
      trimers as a function of reaction coordinates, which reveal a few basins of
      minimal free energy. Associated with them, six major types of stable conformers
      were identified and the structures of transition states between them were also
      determined. We suggest a possible transition mechanism between these conformers
      based on the landscape and structural analysis of the aggregates.

PMID- 19385694
TI  - Thermostabilization mechanism of bovine serum albumin by trehalose.
AB  - Thermal denaturation of bovine serum albumin (BSA) is analyzed from differential
      scanning calorimetry (DSC) and Raman spectroscopy investigations. DSC curves
      exhibit a marked dependence on protein concentration. BSA thermal denaturation
      becomes broader and bimodal, and the temperature of denaturation increases with
      increasing protein concentration. Raman scattering investigations simultaneously
      carried out in the low-frequency range (10-350 cm(-1)) and in the amide I band
      region (1500-1800 cm(-1)) indicate that the denaturation process is described as
      a biphasic process independent of protein concentration. The dependence of the
      protein stability upon the protein concentration can be interpreted from the
      coupling of protein and solvent dynamics. The confrontation of previous results
      obtained from Raman investigations on lysozyme (LYS) and the present study of BSA
      brings out significant information on protein dynamics and the coupling of
      protein and hydration-water dynamics in relation with the solvent accessible
      surface area. Contrary to LYS, the modification of the dynamics of hydration
      water by the protein is clearly observed on BSA. The influence of trehalose on
      the protein dynamics was analyzed. We found that trehalose reduces the dynamic
      fluctuations of polar side chains at the protein-solvent interface. The mechanism
      of thermostabilization by trehalose is related to the reduction of the exposure
      of hydrophobic groups of BSA to the water molecules, and to a strengthening of
      intermolecular O-H interactions in the hydrogen-bond network of water, leading to
      the stabilization of the tertiary structure.

PMID- 19385695
TI  - Weighting formulas for the least-squares analysis of binding phenomena data.
AB  - The rectangular hyperbola, y = abx/(1 + bx), is widely used as a fit model in the
      analysis of data obtained in studies of complexation, sorption, fluorescence
      quenching, and enzyme kinetics. Frequently, the "independent variable" x is
      actually a directly measured quantity, and y may be a simply computed function of
      x, like y = x(0) - x. These circumstances violate one of the fundamental tenets
      of most least-squares methods that the independent variable be error-free and
      they lead to fully correlated error in x and y. Using an effective variance
      approach, we treat this problem to derive weighting formulas for the least
      squares analysis of such data by the given equation and by all of its common
      linearized versions: the double reciprocal, y-reciprocal, and x-reciprocal forms.
      We verify the correctness of these expressions by computing the nonlinear least
      squares parameter standard errors for exactly fitting data, and we confirm their
      utility through Monte Carlo simulations. The latter confirm a problem with
      inversion methods when the inverted data are moderately uncertain ( approximately
      30%), leading to the recommendation that the reciprocal methods not be used for
      such data. For benchmark tests, results are presented for specific data sets
      having error in x alone and in both x and x(0). The actual estimates of a and b
      and their standard errors vary somewhat with the choice of fit model, with one
      important exception: the Deming-Lybanon algorithm treats multiple uncertain
      variables equivalently and returns a single set of parameters and standard errors
      independent of the manner in which the fit model is expressed.

PMID- 19385696
TI  - Functional characteristics of small proteins (70 amino acid residues) forming
      protein-nucleic acid complexes.
AB  - The proteins composed of short polypeptides (about 70 amino acid residues)
      participating in large complexes (ribosome) and proteins interacting with DNA/RNA
      were taken for analysis and classified according to the hydrophobicity
      excess/deficiency distribution as a measure of structural and functional
      specificity and similarity. The characterization of this group of proteins is the
      introductory part to the analysis of the so called "Never Born Proteins" (NBP) in
      search for protein compounds exhibiting biological activity that may be valuable
      in pharmacological research. The entropy scale (classification between random and
      deterministic limits) organized in ranking list allows the comparative analysis
      of the proteins under consideration. The comparison of the hydrophobicity
      deficiency appeared to be useful for similarity recognition, the examples of
      which are shown in the paper. The specificity of proteins participating in large
      protein-nucleic acid complexes generation is presented.

PMID- 19385697
TI  - DNA-Prot: identification of DNA binding proteins from protein sequence
      information using random forest.
AB  - DNA-binding proteins (DNABPs) are important for various cellular processes, such
      as transcriptional regulation, recombination, replication, repair, and DNA
      modification. So far various bioinformatics and machine learning techniques have
      been applied for identification of DNA-binding proteins from protein structure.
      Only few methods are available for the identification of DNA binding proteins
      from protein sequence. In this work, we report a random forest method, DNA-Prot,
      to identify DNA binding proteins from protein sequence. Training was performed on
      the dataset containing 146 DNA-binding proteins and 250 non DNA-binding proteins.
      The algorithm was tested on the dataset containing 92 DNA-binding proteins and
      100 non DNA-binding proteins. We obtained 80.31% accuracy from training and
      84.37% accuracy from testing. Benchmarking analysis on the independent of 823 DNA
      binding proteins and 823 non DNA-binding proteins shows that our approach can
      distinguish DNA-binding proteins from non DNA-binding proteins with more than 80%
      accuracy. We also compared our method with DNAbinder method on test dataset and
      two independent datasets. Comparable performance was observed from both methods
      on test dataset. In the benchmark dataset containing 823 DNA-binding proteins and
      823 non DNA-binding proteins, we obtained significantly better performance from
      DNA-Prot with 81.83% accuracy whereas DNAbinder achieved only 61.42% accuracy
      using amino acid composition and 63.5% using PSSM profile. Similarly, DNA-Prot
      achieved better performance rate from the benchmark dataset containing 88 DNA
      binding proteins and 233 non DNA-binding proteins. This result shows DNA-Prot can
      be efficiently used to identify DNA binding proteins from sequence information.
      The dataset and standalone version of DNA-Prot software can be obtained from
      http://www3.ntu.edu.sg/home/EPNSugan/index_files/dnaprot.htm.

PMID- 19385698
TI  - Binding regularities in complexes of transcription factors with operator DNA:
      homeodomain family.
AB  - In order to disclose general regularities of binding in homeodomain-DNA complexes
      we considered five of them and extended the observed regularities over the entire
      homeodomain family. The five complexes have been selected by similarity of
      protein structures and patterns of contacting residues. Their long range
      interactions and interfaces were compared. The long-range stage of the
      recognition process was characterized by electrostatic potentials about 5
      Angstrom away from molecular surfaces of protein or DNA. For proteins, clear
      positive potential is displayed only at the side contacting the DNA. The double
      chained DNA molecule displays a rather strong negative potential, especially in
      their grooves. Thus, a functional role of electrostatics is a guiding of the
      protein into the DNA major groove, so the protein and DNA could form a loose non
      specific complex. At the close-range stage, neutralization of the phosphate
      charges by positively charged residues is necessary for decreasing the strong
      electrostatic potential of DNA, allowing nucleotide bases to participate in the
      formation of protein-DNA atomic contacts in the interface. The recognizing alpha
      helix of protein was shown to form both invariant and variable groups of contacts
      with DNA by means of certain specific side groups. The invariant contacts
      included highly specific protein-DNA hydrogen bonds between asparagine and
      adenine, nonpolar contacts of hydrophobic amino acids serving as a stereochemical
      barrier for fixing the protein factor on DNA, and an interface cluster of water
      molecules providing local conformational mobility necessary for the dissociation
      process. There is a unique water molecule within the interface that is
      conservative and located at the interface center. Invariant contacts of the
      proteins are mostly formed with the TAAT motif of the promoter DNA forward
      strand. While the invariant contacts specify the family of homeodomains, the
      variable contacts that are formed with the reverse strand of DNA provide
      specificity of individual complexes within the homeodomain family.

PMID- 19385699
TI  - Binding of Hoechst 33258 and its derivatives to DNA.
AB  - In the present work, we employed UV-VIS spectroscopy, fluorescence methods, and
      circular dichroism spectroscopy (CD) to study the interaction of dye Hoechst
      33258, Hoechst 33342, and their derivatives to poly[d(AT)].poly[d(AT)],
      poly(dA).poly(dT), and DNA dodecamer with the sequence 5'-CGTATATATACG-3'. We
      identified three types of complexes formed by Hoechst 33258, Hoechst 33342, and
      methylproamine with DNA, corresponding to the binding of each drug in monomer,
      dimer, and tetramer forms. In a dimer complex, two dye molecules are sandwiched
      in the same place of the minor DNA groove. Our data show that Hoechst 33258,
      Hoechst 33342, and methylproamine also form complexes of the third type that
      reflects binding of dye associates (probably tetramers) to DNA. Substitution of a
      hydrogen atom in the ortho position of the phenyl ring by a methyl group has a
      little effect on binding of monomers to DNA. However it reduces strength of
      binding of tetramers to DNA. In contrast, a Hoechst derivative containing the
      ortho-isopropyl group in the phenyl ring exhibits a low affinity to
      poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] and binds to DNA only in the
      monomer form. This can be attributed to a sterical hindrance caused by the ortho
      isopropyl group for side-by-side accommodation of two dye molecules in the minor
      groove. Our experiments show that mode of binding of Hoechst 33258 derivatives
      and their affinity for DNA depend on substituents in the ortho position of the
      phenyl ring of the dye molecule. A statistical mechanical treatment of binding of
      Hoechst 33258 and its derivatives to a polynucleotide lattice is described and
      used for determination of binding parameters of Hoechst 33258 and its derivatives
      to poly[d(AT)].poly[d(AT)] and poly(dA).poly(dT).

PMID- 19385700
TI  - Inter-helical interactions in membrane proteins: analysis based on the local
      backbone geometry and the side chain interactions.
AB  - The availability of a significant number of the structures of helical membrane
      proteins has prompted us to investigate the mode of helix-helix packing. In the
      present study, we have considered a dataset of alpha-helical membrane proteins
      representing structures solved from all the known superfamilies. We have
      described the geometry of all the helical residues in terms of local coordinate
      axis at the backbone level. Significant inter-helical interactions have been
      considered as contacts by weighing the number of atom-atom contacts, including
      all the side-chain atoms. Such a definition of local axis and the contact
      criterion has allowed us to investigate the inter-helical interaction in a
      systematic and quantitative manner. We show that a single parameter (designated
      as alpha), which is derived from the parameters representing the mutual
      orientation of local axes, is able to accurately capture the details of helix
      helix interaction. The analysis has been carried out by dividing the dataset into
      parallel, anti-parallel, and perpendicular orientation of helices. The study
      indicates that a specific range of alpha value is preferred for interactions
      among the anti-parallel helices. Such a preference is also seen among interacting
      residues of parallel helices, however to a lesser extent. No such preference is
      seen in the case of perpendicular helices, the contacts that arise mainly due to
      the interaction of surface helices with the end of the trans-membrane helices.
      The study supports the prevailing view that the anti-parallel helices are well
      packed. However, the interactions between helices of parallel orientation are non
      trivial. The packing in alpha-helical membrane proteins, which is systematically
      and rigorously investigated in this study, may prove to be useful in modeling of
      helical membrane proteins.

PMID- 19385701
TI  - Molecular dynamics simulations to investigate the structural stability and
      aggregation behavior of the GGVVIA oligomers derived from amyloid beta peptide.
AB  - Several neurodegenerative diseases, such as Alzheimer's, Parkinson's, and
      Huntington's diseases, are associated with amyloid fibrils formed by different
      polypeptides. Recently, the atomic structure of the amyloid-forming peptide
      GGVVIA from the C-terminal hydrophobic segment of amyloid-beta (Abeta) peptide
      has been determined and revealed a dry, tightly self-complementing structure
      between two beta-sheets, termed as "steric zipper". In this study, several all
      atom molecular dynamics simulations with explicit water were conducted to
      investigate the structural stability and aggregation behavior of the GGVVIA
      oligomers with various sizes. The results of our single-layer models suggested
      that the structural stability of the GGVVIA oligomers increases remarkably with
      increasing the numbers of beta-strands. We further identified that SH2-ST2 may
      act as a stable seed in prompting amyloid fibril formations. Our results also
      demonstrated that hydrophobic interaction is the principle driving force to
      stabilize and associate the GGVVIA oligomers between beta-strands; while the
      hydrophobic steric zipper formed via the side chains of V3, V4, and I5 plays a
      critical role in holding the two neighboring beta-sheets together. Single glycine
      substitution at V3, V4, and I5 directly disrupted the hydrophobic steric zipper
      between these two beta-sheets, resulting in the destabilization of the oligomers.
      Our simulation results provided detailed insights into understanding the
      aggregation behavior of the GGVVIA oligomers in the atomic level. It may also be
      helpful for designing new inhibitors able to prevent the fibril formation of
      Abeta peptide.

PMID- 19385702
TI  - Determination of phosphorylation sites for NADP-specific isocitrate dehydrogenase
      from mycobacterium tuberculosis.
AB  - Isocitrate Dehydrogenase (ICD) catalyzes the oxidative decarboxylation reaction
      of 2R,3S-isocitrate to yield 2-oxoglutarate in the Tricarboxylic Acid (TCA)
      cycle. Two isoforms of NADP-specific ICDs with the E.C number 1.1.1.42 have been
      annotated in the organism Mycobacterium tuberculosis, monomeric ICD2 and dimeric
      ICD1. BLAST search against the Protein Data Bank (PDB) database shows a marked
      similarity between dimeric Mycobacterium tuberculosis ICD1 sequence and that of
      Sus scrofa, a cytosolic eukaryotic ICD (65% identity). Escherischia coli ICD
      shows less sequence similarity than the eukaryotic structure. A Homology model
      has thus been built for M. tuberculosis ICD1 using Sus scrofa and human ICD as
      templates. Inactivation of ICD1 by phosphorylation similar to E. coli ICD is
      important to open up the shunt pathway in the TCA cycle, which has been indicated
      in the case of M. tuberculosis. We therefore attempted to identify a number of
      likely phosphorylation sites in M. tuberculosis using pattern prediction and
      checked with the homology models for the accessibility of the peptides containing
      Serine. It was found that the homologous Serine by alignment with E. coli on M.
      tuberculosis ICD1 is difficult to access by specific kinases. Hence other
      probable sites of phosphorylation were checked and three highly probable serine
      containing peptides were identified. The effect of phosphorylation at each of
      these sites was determined by checking the degree of conformational changes, the
      differences caused by the effect of phosphorylation in the active-site and other
      apparent motion different from that of the control, i.e., unphosphorylated M.
      tuberculosis ICD1 model, using molecular dynamics simulations.

PMID- 19385703
TI  - A cost-effective amino-acid-type selective isotope labeling of proteins expressed
      in Leishmania tarentolae.
AB  - We report a cost efficient approach for amino-acid-type selective isotope
      labeling of proteins expressed in Leishmania tarentolae. The method provides an
      economically advantageous alternative to recently established protocol for
      isotopic labeling using expensive synthetic media. The method is based on
      cultivation of the L. tarentolae expression strain in a cheap complex medium
      supplemented with labeled amino acid(s). In this protocol, a labeled amino acid
      is deliberately diluted in the medium of undefined composition, which leads to a
      low-level isotope enrichment upon protein over-expression. The economic advantage
      of the protocol is achieved by avoiding large volumes of expensive synthetic
      medium. Decreased sensitivity of a NMR experiment due to low-level isotope
      enrichment is compensated by a five- to seven-fold increase of the yield of the
      recombinant protein in complex medium as compared to that in the synthetic
      medium. In addition, the decreased sensitivity can be compensated by using a
      higher magnetic field, cryo-detection system or higher number of transients
      during the NMR data acquisition. We show that enrichment as low as 5% does not
      compromise a NMR experiment and makes preparation of the recombinant proteins
      over-expressed in L. tarentolae economically viable. The method is demonstrated
      by selective labeling of the approximately 27 kDa enhanced green fluorescent
      protein (EGFP) with 15N-labeled valine.

PMID- 19385704
TI  - Alignment-free comparison of protein sequences based on reduced amino acid
      alphabets.
AB  - Protein sequences are treated as stochastic processes on the basis of a reduced
      amino acid alphabet of 10 types of amino acids. The realization of a stochastic
      process is described by associated transition probability matrix that corresponds
      to the process uniquely. Then new distances between transition probability
      matrices are defined for sequences similarity analysis. Two separate datasets are
      prepared and tested to identify the validity of the method. The results
      demonstrate the new method is powerful and efficient.

PMID- 19385705
TI  - Sequence analysis, structure prediction, and functional validation of phaC1/phaC2
      genes of Pseudomonas sp. LDC-25 and its importance in polyhydroxyalkanoate
      accumulation.
AB  - Polyhydroxyalkanoates (PHAs) are attractive biomaterials in both conventional
      medical devices and tissue engineering. PHA synthase is responsible for
      catalyzing the formation of Polyhydroxyalkanoates (PHA), but its structural
      information is limited. Hence, this study focuses to predict 3D model for phaC1
      and phaC2 genes of field-soil strain Pseudomonas sp. LDC-25 and to validate the
      functional properties through in vitro studies. The phaC1/phaC2 genes were
      amplified, cloned, and sequenced. The sequence analysis showed > 90% homology to
      phaC loci and presence of alpha/beta hydrolase fold, but phaC2 loci of LDC-25
      exhibits variation in the conserved residue (Ser is replaced by Ala). Threading
      approach demonstrated that Carboxylesterase (d1tqha) can be used as the modeling
      template. The predicted models showed the presence of conserved residues at 122
      (G), 205 (S), and 236 (S). In vitro studies also supported that PHA accumulation
      ability was less in Pseudomonas sp. LDC-25 compared to other field isolate,
      Pseudomonas sp. LDC-5. FT-IR spectrum showed PHA specific peaks at 1735.62 cm(
      1). Results of this study would help to detect the functional domains of the
      protein in order to elucidate their structure/function characteristics with
      special emphasis on invariant conserved residues.

PMID- 19385706
TI  - Modification and modificatory kinetics of the active center of prawn beta-N
      acetyl-D-glucosaminidase.
AB  - Beta-N-acetyl-D-glucosaminidase (NAGase, EC3.2.1.52) plays important role in
      molting, digestion of chitinous foods, and defense systems against parasites in
      prawn (Litopenaeus vannamei). However, study on functional groups and catalytic
      mechanism of NAGase are yet limited. The modification of the active center of
      NAGase from prawn has been first studied. The results demonstrate that the
      disulfide bonds and the carbamidine groups of arginine residues are not essential
      to the enzyme's activity. The modification of indole group of tryptophan of the
      enzyme by N-bromosuccinimide (NBS) can lead to the complete inactivation,
      accompanying the absorption decreasing at 276 nm, indicating that tryptophan is
      essential residue to the enzyme. The modificatory kinetics of NAGase in the
      appropriate concentrations of NBS solution has been studied and the numbers of
      essential tryptophan residues have been determined using the kinetic method of
      the substrate reaction. The result shows that only one tryptophan residue is
      essential for enzyme activity. And the modifications of histidine, lysine
      residue, and the carboxyl groups also inactivate the enzyme completely or
      incompletely. The results showed that the carboxyl groups of acidic amino acid,
      imidazole groups of histidine residue, amino groups of lysine residue, and indole
      group of tryptophan were essential for the activity of enzyme.

PMID- 19385707
TI  - Abstracts of Albany 2009: 16th Conversation. June 16-20 2009. Albany, New York,
      USA.

PMID- 19385708
TI  - Sex differences in pharmacokinetics and pharmacodynamics.
AB  - Significant differences that exist between the sexes affect the prevalence,
      incidence and severity of a broad range of diseases and conditions. Men and women
      also differ in their response to drug treatment. It is therefore essential to
      understand these reactions in order to appropriately conduct risk assessment and
      to design safe and effective treatments. Even from that modest perspective, how
      and when we use drugs can result in unwanted and unexpected outcomes. This review
      summarizes the sex-based differences that impact on pharmacokinetics, and
      includes a general comparison of clinical pharmacology as it applies to men,
      women and pregnant women. Sex-related or pregnancy-induced changes in drug
      absorption, distribution, metabolism and elimination, when significant, may guide
      changes in dosage regimen or therapeutic monitoring to increase its effectiveness
      or reduce potential toxicity. Given those parameters, and our knowledge of sex
      differences, we can derive essentially all factors necessary for therapeutic
      optimization. Since this is a rapidly evolving area, it is essential for the
      practitioner to review drug prescribing information and recent literature in
      order to fully understand the impact of these differences on clinical
      therapeutics.

PMID- 19385709
TI  - Effect of pregnancy on the pharmacokinetics of antihypertensive drugs.
AB  - In the US, approximately 12% of women have hypertension during their pregnancy.
      Antihypertensive drugs are often given to lower maternal blood pressure in those
      with severe hypertension to prevent stroke and hypertensive crises. There is no
      conclusive evidence that antihypertensive treatment is beneficial to the mother
      in mild to moderate hypertension; however, approximately 3% of all pregnant women
      receive an antihypertensive drug at some time during their pregnancy. There are
      only limited data on the effects of pregnancy on the pharmacokinetics of
      antihypertensive drugs. However, knowledge of the pharmacokinetic properties of a
      drug in the nonpregnant adult and use of a mechanistic-based approach allow an
      estimation of the effect of pregnancy on the pharmacokinetics of drugs when data
      are limited or not available. In general, an increased plasma volume and
      decreased protein binding can alter the volume of distribution of the drug.
      Clearance can increase or decrease, depending on the pathway of elimination of
      the drug. Through changes in the volume of distribution and clearance, pregnancy
      can cause a change in the elimination half-life, resulting in the need for
      modification of the dosing frequency. The few studies in pregnant women with
      hypertension have included small numbers of women in the third trimester and
      postpartum, with little or no data in early pregnancy. In addition, many studies
      evaluating the efficacy of antihypertensive medications have been performed using
      dosing regimens of medications that have not been substantiated by
      pharmacological data in pregnant women. There is a need for well designed
      pharmacokinetic and pharmacodynamic studies of antihypertensive medications that
      include analysis during all three trimesters of pregnancy and postpartum. Higher
      doses and altered dosage intervals may be needed for antihypertensive drugs used
      in pregnant women.

PMID- 19385710
TI  - Population pharmacokinetics and dosing recommendations for cisplatin during
      intraperitoneal peroperative administration: development of a limited sampling
      strategy for toxicity risk assessment.
AB  - BACKGROUND: Ovarian cancer is the leading cause of gynaecological cancer-related
      death in Western countries. Intraperitoneal (IP) peroperative chemotherapy is an
      interesting therapeutic option. However, very few data are available regarding
      pharmacokinetics and especially population pharmacokinetics. PATIENTS AND
      METHODS: Thirty-one patients with advanced epithelial cancer classified as
      International Federation of Gynecology and Obstetrics stage IIIC were included in
      the study. Blood and IP samples were taken over a 24-hour period during and after
      IP treatment. Both total and ultrafiltered (Uf) platinum (Pt) concentrations were
      analysed using a population approach with nonlinear mixed-effects modelling
      (NONMEM) software. Improvement of the model with covariates was performed as well
      as assessment of the model using bootstrap and posterior visual predictive
      methods. RESULTS: Both IP fluid and serum pharmacokinetics were satisfactorily
      described with a three-compartment model for both Uf Pt and total Pt
      concentrations. The covariates were bodyweight for the IP volume of distribution
      in the Uf Pt model, and both IP and serum protein concentrations for the
      clearance from the central compartment in the total Pt model. A nomogram, based
      on the results of the Monte Carlo simulations, displays a dose recommendation
      regarding both the risk of renal toxicity and the potent efficacy of the
      treatment. A limited sampling strategy (LSS) allowing the estimation of potential
      risk of renal toxicity is also described. CONCLUSION: The pharmacokinetics of
      cisplatin during peroperative IP chemotherapy could be successfully fitted with
      the present model, which allowed a dosing strategy accompanied by an LSS to
      facilitate the follow-up of patients.

PMID- 19385711
TI  - Defining the role of macrophages in local moxifloxacin tissue concentrations
      using biopsy data and whole-body physiologically based pharmacokinetic modelling.
AB  - OBJECTIVES: This study used a whole-body physiologically based pharmacokinetic
      (WB-PBPK) model for moxifloxacin, plus in vitro and in vivo literature data on
      its interaction with macrophages, to interpret biopsy results generated from
      patients undergoing primarily colorectal surgery. METHODS: A WB-PBPK model was
      developed using PK-Sim(R) software and refined using observed plasma profiles.
      The model was assessed by comparing predictions of unbound interstitial
      concentrations with in vivo data from a microdialysis study. RESULTS:
      Incorporating in vitro data on the percentage volume of macrophages in a
      colorectal resection (8.1%) plus the in vivo kinetic and accumulation potential
      of moxifloxacin in macrophages into the WB-PBPK model, biopsy concentrations and
      kinetics were predicted and compared with observed data. The WB-PBPK model
      accurately described adipose and muscle interstitial unbound concentrations. The
      predicted biopsy concentrations (including interstitial, intracellular, vascular
      space and macrophages) were slightly greater than the observed values, although
      the kinetic (i.e. observed biopsy half-life = 21 hours) was similar to that of
      moxifloxacin in macrophages (20.8 hours) and thus similar to the predicted biopsy
      half-life. A reduction in the predicted biopsy concentrations to match the
      observed data required a decrease in the volume fraction of macrophages from 8.1%
      to 3.6%. CONCLUSION: When plasma concentrations are known, WB-PBPK is a method to
      determine interstitial and intracellular concentrations. In this study,
      integration of biopsy data with WB-PBPK allowed for generation and testing of
      hypotheses to determine the reason for the observed biopsy kinetics. This type of
      translational modelling may lead to a better understanding of the anti-infective
      pharmacokinetic/pharmacodynamic relationship.

PMID- 19385712
TI  - Population pharmacokinetics of orally administered duloxetine in patients:
      implications for dosing recommendation.
AB  - OBJECTIVES: The objectives of this analysis were to characterize the
      pharmacokinetics of duloxetine at steady state in patients, estimate the
      variability, identify significant covariates that may influence duloxetine
      pharmacokinetics and provide appropriate dosing recommendations for patients on
      duloxetine treatment. METHODS: The pharmacokinetic meta-analysis dataset was
      created from one open-label clinical study and four double-blind, placebo
      controlled clinical studies. Duloxetine concentrations (N = 2002) were obtained
      from 594 patients diagnosed with major depressive disorder (n = 223), diabetic
      peripheral neuropathic pain (n = 112), stress urinary incontinence (n = 128) and
      fibromyalgia (n = 131). Patients were given 20-60 mg/day of oral duloxetine once
      or twice daily (the highest dose studied was 120 mg/day). A population
      pharmacokinetic model was developed using a nonlinear mixed-effects modelling
      method. Covariates including bodyweight, age, sex, ethnicity, smoking status,
      disease condition, dose, dosing regimen and creatinine clearance were tested for
      their influence on duloxetine pharmacokinetics. The final model was used to
      predict steady-state duloxetine concentration-time profiles in various patient
      subgroups. RESULTS: Duloxetine pharmacokinetics in patients were described by a
      one-compartmental pharmacokinetic model. The interpatient variability in apparent
      oral clearance (CL/F) was 59% and the interpatient variability in the apparent
      volume of distribution after oral administration (V(d)/F) was 97%. The residual
      error was 31%. Sex, smoking status, age and dose had a statistically significant
      effect on CL/F, whereas the V(d)/F was influenced by ethnicity. CL/F was 40%
      lower in females than in males and 30% lower in nonsmokers than in smokers. CL/F
      decreased with increasing dose and age. The V(d)/F in Hispanic patients was twice
      that of non-Hispanic patients. Simulations showed a considerable overlap in
      duloxetine exposure between the identified patient subgroups. CONCLUSION: Given
      the clinically insignificant change in the magnitude of duloxetine steady-state
      exposure and the considerable overlap in duloxetine exposure between the patient
      subgroups, specific dose recommendations based on sex, smoking status, age, dose
      and ethnicity are not warranted.

PMID- 19385715
TI  - Induction of DNA strand breaks by genotoxicants in the alga Chlamydomonas
      reinhardtii.
AB  - The use of unicellular algae in ecotoxicity testing is well established,
      particularly regarding whole-organism and population-level end points such as
      lethality and population growth. Conflicting information exists, however, on the
      potential for genetic toxicity to be incorporated into the safety studies in this
      test organism. In the present study, DNA strand breaks (Comet assay) and
      ethoxyresorufin-O-deethylase (EROD) activity were used as indicators of genetic
      toxicity and cytochrome P450 1A baseline xenobiotic metabolism, respectively, in
      the unicellular green alga Chlamydomonas reinhardtii. DNA strand breaks were
      quantified following exposure to the direct-acting genotoxic agents 4
      nitroquinoline-1-oxide (NQO) and the N-hydroxy metabolite of 2
      acetylaminofluorene (N-OH-2-AAF) and the indirect-acting genotoxin chrysoidine.
      Following compound exposure, chrysoidine and N-OH-2-AAF produced statistically
      significant increases in DNA strand breaks at both 0.1 and 10 microM and 0.05 and
      5 microM, respectively (p < 0.05 and p < 0.01). Different light sources were also
      found to influence DNA strand breaks, the minimum response being observed using a
      source that omits the ultraviolet range. Compared to many mammalian cells, both
      DNA damage responses and EROD activity were relatively weak. EROD activity was
      0.03 pmol/min/10(6) cells in control cells, and the maximum level of DNA strand
      breaks observed was 14.1% at a 5 nM concentration of NQO. The responses exhibited
      were not enhanced by the use of a cell wall-free mutant strain. In conclusion, C
      reinhardtii responded, albeit weakly, to selected direct- and indirect-acting
      genotoxicants and also exhibited measurable EROD activity.

PMID- 19385713
TI  - Effect of the cytochrome P450 2C19 inhibitor omeprazole on the pharmacokinetics
      and safety profile of bortezomib in patients with advanced solid tumours, non
      Hodgkin's lymphoma or multiple myeloma.
AB  - BACKGROUND AND OBJECTIVE: Bortezomib, an antineoplastic for the treatment of
      relapsed multiple myeloma and mantle cell lymphoma, undergoes metabolism through
      oxidative deboronation by cytochrome P450 (CYP) enzymes, primarily CYP3A4 and
      CYP2C19. Omeprazole, a proton-pump inhibitor, is primarily metabolized by and
      demonstrates high affinity for CYP2C19. This study investigated whether
      coadministration of omeprazole affected the pharmacokinetics, pharmacodynamics
      and safety profile of bortezomib in patients with advanced cancer. The
      variability of bortezomib pharmacokinetics with CYP enzyme polymorphism was also
      investigated. PATIENTS AND METHODS: This open-label, crossover, pharmacokinetic
      drug-drug interaction study was conducted at seven institutions in the US and
      Europe between January 2005 and August 2006. Patients who had advanced solid
      tumours, non-Hodgkin's lymphoma or multiple myeloma, were aged >/=18 years,
      weighed >/=50 kg and had a life expectancy of >/=3 months were eligible. Patients
      received bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 for two 21-day cycles, plus
      omeprazole 40 mg in the morning of days 6-10 and in the evening of day 8 in
      either cycle 1 (sequence 1) or cycle 2 (sequence 2). On day 21 of cycle 2,
      patients benefiting from therapy could continue to receive bortezomib for six
      additional cycles. Blood samples for pharmacokinetic/pharmacodynamic evaluation
      were collected prior to and at various timepoints after bortezomib administration
      on day 8 of cycles 1 and 2. Blood samples for pharmacogenomics were also
      collected. Pharmacokinetic parameters were calculated by noncompartmental
      analysis of plasma concentration-time data for bortezomib administration on day 8
      of cycles 1 and 2, using WinNonlin version 4.0.1.a software. The pharmacodynamic
      profile was assessed using a whole-blood 20S proteasome inhibition assay.
      RESULTS: Twenty-seven patients (median age 64 years) were enrolled, 12 in
      sequence 1 and 15 in sequence 2, including eight and nine pharmacokinetic
      evaluable patients, respectively. Bortezomib pharmacokinetic parameters were
      similar when bortezomib was administered alone or with omeprazole (maximum plasma
      concentration 120 vs 123 ng/mL; area under the plasma concentration-time curve
      from 0 to 72 hours 129 vs 135 ng . h/mL). The pharmacodynamic parameters were
      also similar (maximum effect 85.8% vs 93.7%; area under the percent inhibition
      time curve over 72 hours 4052 vs 3910 % x h); the differences were not
      statistically significant. Pharmacogenomic analysis revealed no meaningful
      relationships between CYP enzyme polymorphisms and
      pharmacokinetic/pharmacodynamic parameters. Toxicities were generally similar
      between patients in sequence 1 and sequence 2, and between cycle 1 and cycle 2 in
      both treatment sequences. Among 26 evaluable patients, 13 (50%) were assessed as
      benefiting from bortezomib at the end of cycle 2 and continued to receive
      treatment. CONCLUSION: No impact on the pharmacokinetics, pharmacodynamics and
      safety profile of bortezomib was seen with coadministration of omeprazole.
      Concomitant administration of bortezomib and omeprazole is unlikely to cause
      clinically significant drug-drug interactions and is unlikely to have an impact
      on the efficacy or safety of bortezomib.

PMID- 19385716
TI  - Seroprevalence of Toxoplasma gondii and concurrent Bartonella spp., feline
      immunodeficiency virus, and feline leukemia virus infections in cats from
      Grenada, West Indies.
AB  - Toxoplasma gondii and Bartonella spp. are zoonotic pathogens of cats. Feline
      immunodeficiency virus (FIV) and feline leukemia virus (FeLv) are related to
      human immunodeficiency virus, and human leukemia virus, respectively; all of
      these viruses are immunosuppressive. In the present study, the prevalence of
      antibodies to T. gondi, Bartonella spp., FIV, as well as FeLv antigen were
      determined in sera from 75 domestic and 101 feral cats (Felis catus) from the
      Caribbean island of Grenada, West Indies. Using a modified agglutination test,
      antibodies to T. gondii were found in 23 (30.6%) of the 75 pet cats with titers
      of 1:25 in 1, 1:50 in 3, 1:400 in 4, 1:500 in 12, 1:800 in 2, and 1:1,600 in 1,
      and 28 (27.7%) of 101 feral cats with titers of 1:25 in 4, 1:50 in 7, 1:200 in 4,
      1:400 in 1, 1:500 in 3, 1:800 in 2, 1:1,600 in 3, and 1:3,200 in 4. Overall, in
      both pet and feral cats, the seroprevalence increased with age. Antibodies to
      Bartonella spp. were found in 38 (50.6%) of the 75 pet cats and 52.4% of 101
      feral cats. Antibodies to FIV were found in 6 domestic and 22 feral cats. None of
      the 176 cats was positive for FeLv antigen. There was no correlation among T.
      gondii, Bartonella spp., and FIV seropositivity.

PMID- 19385717
TI  - Self-organization of dynein motors generates meiotic nuclear oscillations.
AB  - Meiotic nuclear oscillations in the fission yeast Schizosaccharomyces pombe are
      crucial for proper chromosome pairing and recombination. We report a mechanism of
      these oscillations on the basis of collective behavior of dynein motors linking
      the cell cortex and dynamic microtubules that extend from the spindle pole body
      in opposite directions. By combining quantitative live cell imaging and laser
      ablation with a theoretical description, we show that dynein dynamically
      redistributes in the cell in response to load forces, resulting in more dynein
      attached to the leading than to the trailing microtubules. The redistribution of
      motors introduces an asymmetry of motor forces pulling in opposite directions,
      leading to the generation of oscillations. Our work provides the first direct in
      vivo observation of self-organized dynamic dynein distributions, which, owing to
      the intrinsic motor properties, generate regular large-scale movements in the
      cell.

PMID- 19385718
TI  - A cell cycle timer for asymmetric spindle positioning.
AB  - The displacement of the mitotic spindle to one side of a cell is important for
      many cells to divide unequally. While recent progress has begun to unveil some of
      the molecular mechanisms of mitotic spindle displacement, far less is known about
      how spindle displacement is precisely timed. A conserved mitotic progression
      mechanism is known to time events in dividing cells, although this has never been
      linked to spindle displacement. This mechanism involves the anaphase-promoting
      complex (APC), its activator Cdc20/Fizzy, its degradation target cyclin, and
      cyclin-dependent kinase (CDK). Here we show that these components comprise a
      previously unrecognized timer for spindle displacement. In the Caenorhabditis
      elegans zygote, mitotic spindle displacement begins at a precise time, soon after
      chromosomes congress to the metaphase plate. We found that reducing the function
      of the proteasome, the APC, or Cdc20/Fizzy delayed spindle displacement.
      Conversely, inactivating CDK in prometaphase caused the spindle to displace
      early. The consequence of experimentally unlinking spindle displacement from this
      timing mechanism was the premature displacement of incompletely assembled
      components of the mitotic spindle. We conclude that in this system, asymmetric
      positioning of the mitotic spindle is normally delayed for a short time until the
      APC inactivates CDK, and that this delay ensures that the spindle does not begin
      to move until it is fully assembled. To our knowledge, this is the first
      demonstration that mitotic progression times spindle displacement in the
      asymmetric division of an animal cell. We speculate that this link between the
      cell cycle and asymmetric cell division might be evolutionarily conserved,
      because the mitotic spindle is displaced at a similar stage of mitosis during
      asymmetric cell divisions in diverse systems.

PMID- 19385719
TI  - From rapid place learning to behavioral performance: a key role for the
      intermediate hippocampus.
AB  - Rapid place encoding by hippocampal neurons, as reflected by place-related
      firing, has been intensely studied, whereas the substrates that translate
      hippocampal place codes into behavior have received little attention. A key point
      relevant to this translation is that hippocampal organization is characterized by
      functional-anatomical gradients along the septotemporal axis: Whereas the ability
      of hippocampal neurons to encode accurate place information declines from the
      septal to temporal end, hippocampal connectivity to prefrontal and subcortical
      sites that might relate such place information to behavioral-control processes
      shows an opposite gradient. We examined in rats the impact of selective lesions
      to relevant parts of the hippocampus on behavioral tests requiring place learning
      (watermaze procedures) and on in vivo electrophysiological models of hippocampal
      encoding (long-term potentiation [LTP], place cells). We found that the
      intermediate hippocampus is necessary and largely sufficient for behavioral
      performance based on rapid place learning. In contrast, a residual septal pole of
      the hippocampus, although displaying intact electrophysiological indices of rapid
      information encoding (LTP, precise place-related firing, and rapid remapping),
      failed to sustain watermaze performance based on rapid place learning. These data
      highlight the important distinction between hippocampal encoding and the
      behavioral performance based on such encoding, and suggest that the intermediate
      hippocampus, where substrates of rapid accurate place encoding converge with
      links to behavioral control, is critical to translate rapid (one-trial) place
      learning into navigational performance.

PMID- 19385720
TI  - Target genes of the MADS transcription factor SEPALLATA3: integration of
      developmental and hormonal pathways in the Arabidopsis flower.
AB  - The molecular mechanisms by which floral homeotic genes act as major
      developmental switches to specify the identity of floral organs are still largely
      unknown. Floral homeotic genes encode transcription factors of the MADS-box
      family, which are supposed to assemble in a combinatorial fashion into organ
      specific multimeric protein complexes. Major mediators of protein interactions
      are MADS-domain proteins of the SEPALLATA subfamily, which play a crucial role in
      the development of all types of floral organs. In order to characterize the roles
      of the SEPALLATA3 transcription factor complexes at the molecular level, we
      analyzed genome-wide the direct targets of SEPALLATA3. We used chromatin
      immunoprecipitation followed by ultrahigh-throughput sequencing or hybridization
      to whole-genome tiling arrays to obtain genome-wide DNA-binding patterns of
      SEPALLATA3. The results demonstrate that SEPALLATA3 binds to thousands of sites
      in the genome. Most potential target sites that were strongly bound in wild-type
      inflorescences are also bound in the floral homeotic agamous mutant, which
      displays only the perianth organs, sepals, and petals. Characterization of the
      target genes shows that SEPALLATA3 integrates and modulates different growth
      related and hormonal pathways in a combinatorial fashion with other MADS-box
      proteins and possibly with non-MADS transcription factors. In particular, the
      results suggest multiple links between SEPALLATA3 and auxin signaling pathways.
      Our gene expression analyses link the genomic binding site data with the
      phenotype of plants expressing a dominant repressor version of SEPALLATA3,
      suggesting that it modulates auxin response to facilitate floral organ outgrowth
      and morphogenesis. Furthermore, the binding of the SEPALLATA3 protein to cis
      regulatory elements of other MADS-box genes and expression analyses reveal that
      this protein is a key component in the regulatory transcriptional network
      underlying the formation of floral organs.

PMID- 19385721
TI  - Treatment of HIV infection with raltegravir.
AB  - BACKGROUND: Raltegravir, an inhibitor of the HIV-1 integrase enzyme, is now
      available for the treatment of drug-resistant virus. OBJECTIVE: To establish
      raltegravir as an effective addition to the existing antiretroviral armamentarium
      by reviewing pharmacokinetics, efficacy, safety and tolerability. METHODS: Data
      from pharmacokinetic, Phase II and III clinical trials were reviewed.
      RESULTS/CONCLUSIONS: Results from clinical trials indicate that raltegravir is
      safe and highly effective in the treatment of both antiretroviral-naive and 
      experienced patients.

PMID- 19385722
TI  - Integrated imaging approach with MEG and DTI to detect mild traumatic brain
      injury in military and civilian patients.
AB  - Traumatic brain injury (TBI) is a leading cause of sustained impairment in
      military and civilian populations. However, mild (and some moderate) TBI can be
      difficult to diagnose due to lack of obvious external injuries and because the
      injuries are often not visible on conventional acute MRI or CT. Injured brain
      tissues in TBI patients generate pathological low-frequency neuronal magnetic
      signal (delta waves 1-4 Hz) that can be measured and localized by
      magnetoencephalography (MEG). We hypothesize that abnormal MEG delta waves
      originate from gray matter neurons that experience de-afferentation due to axonal
      injury to the underlying white matter fiber tracts, which is manifested on
      diffusion tensor imaging (DTI) as reduced fractional anisotropy. The present
      study used a neuroimaging approach integrating findings of magnetoencephalography
      (MEG) and diffusion tensor imaging (DTI), evaluating their utility in diagnosing
      mild TBI in 10 subjects in whom conventional CT and MRI showed no visible lesions
      in 9. The results show: (1) the integrated approach with MEG and DTI is more
      sensitive than conventional CT and MRI in detecting subtle neuronal injury in
      mild TBI; (2) MEG slow waves in mild TBI patients originate from cortical gray
      matter areas that experience de-afferentation due to axonal injuries in the white
      matter fibers with reduced fractional anisotropy; (3) findings from the
      integrated imaging approach are consistent with post-concussive symptoms; (4) in
      some cases, abnormal MEG delta waves were observed in subjects without obvious
      DTI abnormality, indicating that MEG may be more sensitive than DTI in diagnosing
      mild TBI.

PMID- 19385724
TI  - Engineering functional islets from cultured cells.
AB  - OBJECTIVE: Although pancreatic islet transplantation can now be performed
      minimally invasively in patients with type 1 diabetes, the availability of
      functional islet donors remains the chief obstacle to widespread clinical
      application. Tissue engineering islet cells in vitro that function when implanted
      in vivo provides a solution to this problem. RESEARCH DESIGN AND METHODS: Rat
      pancreatic islets were enzymatically dissociated into a single-cell suspension
      and seeded onto a polyglycolic acid (PGA) scaffold. The cells were cultured in
      CMRL 1099 medium containing epidermal growth factor, nerve growth factor, and
      insulin-like growth factor for 5 days. The PGA and isolated cells were then
      suspended in a thermoreversible gelatin polymer (TGP) with insulin, transferring
      and selenous acid, in F-12 and Dulbecco's modified Eagle's medium, to proliferate
      over a 40-day period. After the degradation of the PGA fibers, the TGP was
      removed using cold temperature extraction. The tissue-engineered (TE) islets were
      then collected manually and transplanted beneath the kidney capsule of
      Streptozotocin (STZ)-induced diabetic nude mice. RESULTS: All mice that received
      the TE islets reverted from the induced hyperglycemic state to a state of
      normoglycemia (n = 6). The treated mice demonstrated normal oral glucose
      tolerance tests. Testing for the species-specific C-peptide allowed
      discrimination between the exogenous insulin secretions of the TE rat islets and
      the endogenous secretions of the nude mice. Immunohistochemistry confirmed the
      multilineage potential of these TE endocrine cells, showing them capable of
      secreting insulin, glucagon, and somatostatin. CONCLUSIONS: The ability to tissue
      engineer pancreatic islets in vitro, through use of PGA and TGP, that fully
      function in vivo to return diabetic-induced mice to state of normoglycemia has
      potential implications for the treatment type 1 diabetes.

PMID- 19385725
TI  - A novel cylindrical biaxial computer-controlled bioreactor and biomechanical
      testing device for vascular tissue engineering.
AB  - It is becoming evident that tissue-engineered constructs adapt to altered
      mechanical loading, and that specific combinations of multidirectional loads
      appear to have a synergistic effect on the remodeling. However, most studies of
      mechanical stimulation of engineered vascular tissue engineering employ only
      uniaxial stimulation. Here we present a novel computer-controlled bioreactor and
      biomechanical testing device designed to precisely and simultaneously control
      mean and cyclic values of transmural pressure (at rates up to 1 Hz and ranges of
      40 mmHg), luminal flow rate, and axial length (or load) applied to gel-derived,
      scaffold-derived, and self-assembly-derived tissue-engineered blood vessels
      during culture, while monitoring vessel geometry with a resolution of 6.6 mum.
      Intermittent monitoring of the extracellular matrix and cells is accomplished on
      live tissues using multi-photon confocal microscopy under unloaded and loaded
      conditions at multiple time-points in culture (on the same vessel) to quantify
      changes in cell and extracellular matrix content and organization. This same
      device is capable of performing intermittent cylindrical biaxial biomechanical
      testing at multiple time-points in culture (on the same vessel) to quantify
      changes in the mechanical behavior during culture. Here we demonstrate the
      capabilities of this new device on self-assembly-derived and collagen-gel-derived
      tissue-engineered blood vessels.

PMID- 19385726
TI  - Resurrected pandemic influenza viruses.
AB  - Influenza viruses continue to pose a major global public health problem. There is
      a need to better understand the pathogenicity and transmission of pandemic
      influenza viruses so that we may develop improved methods for their prevention
      and control. Reconstruction of the 1918 virus and studies elucidating the
      exceptional virulence and transmissibility of the virus are providing exciting
      new insights into this devastating pandemic strain. The primary approach has been
      to reconstruct and analyze recombinant viruses, in which genes of the 1918 virus
      are replaced with genes of contemporary influenza viruses of lesser virulence.
      This review highlights the current status of the field and discusses the
      molecular determinants of the 1918 pandemic virus that may have contributed to
      its virulence and spread. Identifying the exact genes responsible for the high
      virulence of the 1918 virus will be an important step toward understanding
      virulent influenza strains and will allow the world to better prepare for and
      respond to future influenza pandemics.

PMID- 19385728
TI  - Community ecology of fungal pathogens causing wheat head blight.
AB  - Research on the pathogen components involved in Fusarium head blight (FHB) along
      with the effects of their interactions on disease development and mycotoxin
      accumulation is reviewed. The fungal components within the FHB complex differ
      significantly in different environments. Individual species may respond
      differently to, and be differentially influenced by, particular disease control
      measures. Almost all published co-inoculation studies on wheat spikes or grains
      show that competitive interactions among FHB pathogens are the rule when
      fungal/disease development is considered. However, the fungi with the competitive
      advantage do not usually gain any advantage from the presence of other weaker
      competing fungi. Total mycotoxin production in mixed inoculations may decrease,
      increase, or remain unchanged compared with single-isolate inoculations,
      depending on the fungal species concerned and environmental conditions. A few
      recent studies, where each individual fungal component was quantified using
      molecular methods, suggest that mycotoxin productivity in mixed inoculations
      generally increases.

PMID- 19385727
TI  - Regulation of translation initiation by RNA binding proteins.
AB  - RNA binding proteins are capable of regulating translation initiation by a
      variety of mechanisms. Although the vast majority of these regulatory mechanisms
      involve translational repression, one example of translational activation has
      been characterized in detail. The RNA recognition targets of these regulatory
      proteins exhibit a wide range in structural complexity, with some proteins
      recognizing complex pseudoknot structures and others binding to simple RNA
      hairpins and/or short repeated single-stranded sequences. In some instances the
      bound protein directly competes with ribosome binding, and in other instances the
      bound protein promotes formation of an RNA structure that inhibits ribosome
      binding. Examples also exist in which the bound protein traps the ribosome in a
      complex that is incapable of initiating translation.

PMID- 19385729
TI  - Plant disease diagnostic capabilities and networks.
AB  - Emerging, re-emerging and endemic plant pathogens continue to challege our
      ability to safeguard plant health worldwide. Further, globalization, climate
      change, increased human mobility, and pathogen and vector evolution have combined
      to increase the spread of invasive plant pathogens. Early and accurate diagnoses
      and pathogen surveillance on local, regional, and global scales are necessary to
      predict outbreaks and allow time for development and application of mitigation
      strategies. Plant disease diagnostic networks have developed worldwide to address
      the problems of efficient and effective disease diagnosis and pathogen detection,
      engendering cooperation of institutions and experts within countries and across
      national borders. Networking maximizes impact in the face of shrinking government
      investments in agriculture and diminishing human resource capacity in diagnostics
      and applied pathology. New technologies promise to improve the speed and accuracy
      of disease diagnostics and pathogen detection. Widespread adoption of standard
      operating procedures and diagnostic laboratory accreditation serve to build trust
      and confidence among institutions. Case studies of national, regional, and
      international diagnostic networks are presented.

PMID- 19385730
TI  - Diversity, pathogenicity, and management of verticillium species.
AB  - The genus Verticillium encompasses phytopathogenic species that cause vascular
      wilts of plants. In this review, we focus on Verticillium dahliae, placing
      emphasis on the controversy surrounding the elevation of a long-spored variant as
      a new species, recent advances in the analysis of compatible and incompatible
      interactions, highlighted by the use of strains expressing fluorescent proteins,
      and the genetic diversity among Verticillium spp. A synthesis of the approaches
      to explore genetic diversity, gene flow, and the potential for cryptic
      recombination is provided. Control of Verticillium wilt has relied on a panoply
      of chemical and nonchemical strategies, but is beset with environmental or site
      specific efficacy problems. Host resistance remains the most logical choice, but
      is unavailable in most crops. The genetic basis of resistance to Verticillium
      wilt is unknown in most crops, as are the subcellular signaling mechanisms
      associated with Ve-mediated, race-specific resistance. Increased understanding in
      each of these areas promises to facilitate management of Verticillium wilts
      across a broad range of crops.

PMID- 19385731
TI  - Look before you leap: memoirs of a "cell biological" plant pathologist.
AB  - In this article, I recount how I became a plant pathologist and used clues
      derived from light and electron microscopy to direct my research on the
      interactions between plants and biotrophic fungi. Examples of the value of
      microscopic examination are described for investigations of host compatibility,
      the hypersensitive response, nonhost resistance, and the evolution of host
      parasite specificity.

PMID- 19385734
TI  - Lack of evidence for human herpesvirus-8 transmission via blood transfusion in a
      historical US cohort.
AB  - BACKGROUND: Recent studies have found evidence of occasional human herpesvirus
      (HHV)-8 transmission via blood transfusion. However, because these studies were
      conducted outside the United States or did not have linked donor-recipient pairs,
      they have a limited ability to inform US blood-banking policy. METHODS: We
      investigated HHV-8 transmission via blood transfusion in the United States by
      conducting HHV-8 serologic testing among participants of the Transfusion
      Transmitted Viruses Study (TTVS), who enrolled during the 1970s. RESULTS: HHV-8
      seroprevalence was 2.8% (29/1023) among blood donors, 7.1% (96/1350) among
      transfusion recipients, 7.7% (46/599) among surgical control patients who did not
      receive transfusions, and 96.3% (77/80) among control patients with Kaposi
      sarcoma. One transfusion recipient seroconverted (0.08% [1/1259]), but this
      patient did not receive any HHV-8-seropositive blood units, suggesting that the
      infection was not related to blood transfusion. One of the surgical control
      patients who did not receive transfusions also seroconverted (0.18% [1/556]).
      Rates of seroconversion were 1.6 per 1000 person-years (95% confidence interval
      [CI], 0.04-8.9 per 1000 person-years) for the transfusion recipients and 3.6 per
      1000 person-years (95% CI, 0.09-20.1 per 1000 person-years) for the surgical
      control patients who did not receive transfusions (P = .61). CONCLUSIONS: Rates
      of HHV-8 seroconversion in the transfusion and nontransfusion groups were not
      statistically different, and the historical nature of the cohort (e.g., before
      leukoreduction) suggests that any current transmission via blood transfusion is
      rare.

PMID- 19385733
TI  - Tuberculosis treatment and risk of stavudine substitution in first-line
      antiretroviral therapy.
AB  - BACKGROUND: Treatment for tuberculosis (TB) is common among individuals receiving
      stavudine-containing highly active antiretroviral therapy (HAART), but the effect
      of TB treatment on stavudine toxicity has received little attention. We estimated
      the effect of TB treatment on risk of stavudine substitution among individuals
      receiving first-line HAART. METHODS: We evaluated a cohort of 7066 patients who
      initiated HAART from April 2004 through March 2007 in Johannesburg, South Africa.
      Three exposure categories were considered: ongoing TB treatment at HAART
      initiation, concurrent initiation of TB treatment and HAART, and incident TB
      treatment after HAART initiation. The outcome was single-drug stavudine
      substitution. Adjusted hazard ratios (aHRs) were estimated using marginal
      structural models to control for confounding, loss to follow-up, and competing
      risks. RESULTS: Individuals with ongoing and concurrent TB treatment were at
      increased risk of stavudine substitution, irrespective of stavudine dosage. For
      ongoing TB treatment, aHR was 3.18 (95% confidence interval [CI], 1.82-5.56) in
      the first 2 months of HAART, 2.51 (95% CI, 1.77-3.54) in months 3-6, and 1.19
      (95% CI, 0.94-1.52) thereafter. For concurrent TB treatment, aHR was 6.60 (95%
      CI, 3.03-14.37) in the first 2 months, 1.88 (95% CI, 0.87-4.09) in months 3-6,
      and 1.07 (95% CI, 0.65-1.76) thereafter. There was no effect of incident TB on
      stavudine substitution risk. CONCLUSIONS: Risk of stavudine substitution was
      increased among patients who received TB treatment and was especially elevated
      during the period soon after HAART initiation. In settings in which alternative
      antiretroviral drugs are available, initiation of stavudine therapy in patients
      receiving TB treatment may need to be reconsidered.

PMID- 19385735
TI  - Protective immunity afforded by inactivated H5N1 (NIBRG-14) vaccine requires
      antibodies against both hemagglutinin and neuraminidase in mice.
AB  - BACKGROUND: Hemagglutination-inhibition (HI) antibody titers correlate with
      protective immunity to seasonal influenza viruses. However, inactivated H5N1
      influenza vaccines from Vietnam 2004 strains afford protection without producing
      high or even detectable HI antibodies. METHODS: BALB/c mice were immunized twice
      (at a 3-week interval) with inactivated whole-virus influenza vaccine produced
      using reverse genetics, with the internal genes of A/PR/8/34 (a high-yield
      strain) and the hemagglutinin (HA) and neuraminidase (NA) genes of
      A/Vietnam/1194/04 (H5N1) virus (NIBRG-14) adjuvanted with alum (5 microg of HA).
      Either HA- or NA-binding antibodies were absorbed from the immune serum. The
      protective efficacy of these antibodies was determined by injecting the absorbed
      serum into severe combined immunodeficiency mice, which were then challenged with
      highly pathogenic H5N1 virus (A/Vietnam/Jp1203/2004; Japanese isolate of
      A/Vietnam/1203/2004). RESULTS: The NIBRG-14 vaccine elicited levels of anti-HA
      antibodies similar to levels elicited by the H1N1 vaccines, as well as levels of
      anti-NA antibodies higher than those elicited by the H1N1 vaccines. The
      absorption of either anti-HA or anti-NA antibody from immune serum samples
      obtained from NIBRG-14-vaccinated mice significantly reduced the protective
      efficacy of the serum. CONCLUSIONS: For NIBRG-14 vaccines to confer protection to
      vaccinated hosts, both anti-HA and anti-NA antibodies are required. This finding
      implies that the measurement of both antibody levels may be required for accurate
      evaluation of vaccine efficacy.

PMID- 19385736
TI  - An assessment of donor-to-recipient transmission patterns of human
      cytomegalovirus by analysis of viral genomic variants.
AB  - BACKGROUND: We studied human cytomegalovirus (CMV) donor-to-recipient
      transmission patterns in organ transplantation by analyzing genomic variants on
      the basis of CMV glycoprotein B (gB) genotyping. METHODS: Organ transplant
      recipients were included in the study if they had CMV viremia, if they had
      received an organ from a CMV-seropositive donor, and if there was at least 1
      other recipient of an organ from the same donor who developed CMV viremia.
      Genotypes (gB1-4) were determined by real-time polymerase chain reaction.
      RESULTS: Forty-seven recipients of organs from 21 donors developed CMV viremia.
      Twenty-three recipients had a pretransplant donor/recipient (D/R) CMV serostatus
      of D(+)/R(+), and 24 had a serostatus of D(+)/R(-). The prevalences of genotypes
      in recipients were as follows: for gB1, 51% (n = 24); for gB2, 19% (n = 9); for
      gB3, 9% (n = 4); for gB4, 0% (n = 0); and for mixed infection, 21% (n = 10).
      Recipients of an organ from a common donor had infection with CMV of the same gB
      genotype in 12 (57%) of 21 instances. Concordance between genotypes was higher
      among seronegative (i.e., D(+)/R(-)) recipients than among seropositive
      (D(+)/R(+)) recipients, although discordances resulting from the transmission of
      multiple strains were seen. In seropositive recipients, transmission of multiple
      strains from the donor could not be differentiated from reactivation of a
      recipient's own strains. CONCLUSION: Our analysis of strain concordance among
      recipients of organs from common donors showed that transmission of CMV has
      complex dynamic patterns. In seropositive recipients, transmission or
      reactivation of multiple CMV strains is possible.

PMID- 19385737
TI  - Use of blood-donor and transfusion-recipient biospecimen repositories to address
      emerging blood-safety concerns and advance infectious disease research: the
      National Heart, Lung, and Blood Institute Biologic Specimen Repository.

PMID- 19385741
TI  - Introduction to special issue: advancing the ethics of community-based
      participatory research.
AB  - Increasingly communities are engaging in community-based participatory research
      (CBPR) to address their pressing health concerns, frequently in partnership with
      institutions. CBPR with its underlying values challenges us to expand the
      traditional framework of ethical analysis to include community-level and
      partnership-oriented considerations. This special issue considers ethical
      considerations inherent in CBPR, presents examples of how communities have
      created their own processes for research ethics review, and identifies challenges
      CBPR teams may encounter with institution-based research ethics committees.
      Drawing upon the special issue articles and the work conducted by Community
      Campus Partnerships for Health and the Tuskegee University National Center for
      Bioethics in Research and Health Care, we propose an approach and a set of
      strategies to create a system of research ethics review that more fully accounts
      for individual and community-level considerations.

PMID- 19385742
TI  - Creating community-based participatory research in a diverse community: a case
      study.
AB  - Communities struggle to create research guidelines for ethical collaborative
      research within their locale. In Lawrence, Massachusetts (USA) a collaborative
      group of community members and academic researchers, known as the Mayor's Health
      Task Force Research Initiative Working Group, took on the challenge of creating
      guidelines for ethical community-based research. This case study of the Task
      Force's work addresses questions of research ethics in a diverse community where
      families struggle with few resources and face many health disparities, under the
      often-intrusive and unhelpful scrutiny of researchers from the many nearby major
      research universities. Representatives from the city, community organizations,
      and research universities developed a set of core ethical principles for research
      partnerships, a list of criteria for agreements between partners, and a model to
      help guide researchers and community members toward equitable and mutually
      beneficial research. This model can be generalized to similar other communities.

PMID- 19385743
TI  - Balancing power among academic and community partners: the case of El Proyecto
      Bienestar.
AB  - Balancing power among academic and community partners, addressing community
      identified needs, and strengthening community capacity are ethical values unique
      to community-based participatory research (CBPR). Negotiation of these values in
      one CBPR environmental justice project was evaluated to advance the environmental
      and occupational health of a Hispanic agricultural community in central
      Washington State. Data were collected through document review and participant
      observation. Applied conversation and discourse analysis were used to interpret
      the data. Within the organization, farmworkers primarily served an advisory role.
      Facilitation style influenced how participants negotiated environmental justice.
      Research goals were advanced in the project, but no direct actions were taken to
      improve farmworker health. Implementing CBPR's ethical values requires a
      willingness to confront institutional and interpersonal challenges, and offers a
      vision of research that builds knowledge and strengthens communities.

PMID- 19385744
TI  - Enacting research ethics in partnerships with indigenous communities in Canada:
      "Do it in a good way".
AB  - Two studies conducted through community-campus partnerships demonstrated emerging
      frameworks for ethical conduct of research involving Indigenous peoples in
      Canada. Both projects involved multiple Indigenous community partners whose
      interests in promoting children's development and fathers' involvement motivated
      the projects. The Indigenous projects were conceived within a broader social
      agenda of restorative justice and self-determination of Indigenous peoples in
      Canada following centuries of colonial government interventions. Guiding
      principles included community relevance, community participation, mutual capacity
      building, and benefit to Indigenous communities. Memoranda of Understanding
      negotiated with each community partner specified the roles of community and
      university partners and research team members in each phase of the research.
      Testimonials obtained from community representatives before and after the
      research projects indicated the success of the projects in yielding benefits to
      the communities in the form of substantive knowledge and strengthened capacities
      to engage in collaborative research through community-campus partnerships. The
      larger collaborative research projects in which these two Indigenous projects
      were embedded created challenges and opportunities due to varying recognition
      within these networks of the primacy of relationships as a foundation for
      research and the indeterminacy of outcomes when ownership of data and control
      over dissemination is in the hands of community partners.

PMID- 19385745
TI  - Developing a participatory Aboriginal health research project: "Only if it's
      going to mean something".
AB  - Community-based research methods were used in a study of health needs with the
      Wikwemikong Unceded Indian Reserve, Ontario, Canada based on critical theory,
      Indigenous teachings and participatory action research (PAR). The process of
      developing the project led to the elucidation of eight key principles deemed
      necessary for the development of a project that is both culturally and community
      appropriate: partnership, empowerment, community control, mutual benefit,
      wholism, action, communication and respect. Adherence to these eight principles
      appears necessary for an ethical and an effective research process in Aboriginal
      communities.

PMID- 19385746
TI  - Variability in institutional approaches to ethics review of community-based
      research conducted in collaboration with unaffiliated organizations.
AB  - Academic institutions' requirements FOR ethics committee (IRB) review of research
      conducted by investigators from unaffiliated organizations engaged in
      collaborative, community-based research (CBR) may be highly variable. The present
      study examined the extent of this variability through a national survey of 196
      IRB directors from US academic institutions. Fifty-three percent of respondents
      reported a formal policy or standardized approach to reviewing this type of CBR,
      with high volume IRBs more likely than low volume IRBs to do so (aOR 2.11, 95% CI
      1.02, 4.35). The most common policy (40%) was to require that unaffiliated
      community organizations obtain a Federalwide Assurance on which they delegate
      responsibility for IRB review to their own (i.e., the academic institution's)
      IRB. Among IRBs without formal policies, 56% reported that human subject risk was
      their foremost consideration when reviewing CBR. Universities (71%) were more
      likely than medical schools (33%) to report subject risk as their foremost
      consideration (aOR 4.68, 95% CI 1.43, 15.28).

PMID- 19385747
TI  - An HIV prevention protocol reviewed at 15 national sites: how do ethics
      committees protect communities?
AB  - To learn whether ethics committees reviewing community-based participatory
      research concentrate on the protection of communities, in addition to individual
      participants, data from 15 sites were analyzed. Eighty-two ethics committee
      concerns related to consent (35%), protocol procedures (49%), data collection
      (17%), and HIPAA (6%) were identified. Concerns generally involved individual
      level subject issues; only 17% were related to community issues. To improve
      community-level protections in research, the authors recommend that both ethics
      committee members and research staff receive education concerning protection and
      respect for communities, that a community member group be established to advise
      researchers throughout the planning and implementation of community-level studies
      and that local ethics committee boards include members with community-level
      experience.

PMID- 19385748
TI  - Educational advantage.
AB  - This special issue of JERHRE focuses on ethical considerations in community-based
      participatory research (CBPR), including IRB practices, partnerships, and CBPR in
      Aboriginal and Indigenous communities. This Educational Advantage section
      presents discussion questions relating to the range of issues raised across the
      different articles. While separate questions are identified for each of the
      articles, we encourage readers to borrow relevant ideas from other articles in
      this issue when answering questions. For example, in responding to the Lawrence
      Research Initiative Working Group questions, what further insight can be gained
      from the articles written by Postma or Jacklin and Kinoshameg? We encourage you
      to discuss the following questions in small groups, as the group process will
      deepen your insights.

PMID- 19385752
TI  - Earning trust.

PMID- 19385753
TI  - Partnering for Care in HIV Prevention Trials.
AB  - QUALITATIVE CASE STUDIES WERE conducted at seven international sites conducting
      HIV prevention research in Africa, Asia, and the Americas to identify strategies
      for ensuring that health needs of research participants identified in the course
      of research are adequately addressed. Key factors were identified that contribute
      to the balance between direct care and healthcare referrals at a research site,
      as well as the overall quality of the healthcare made available to research
      participants. The case studies exemplify the concept of "moral negotiation" in
      research (Weijer & LeBlanc, 2006), that is, a process where researchers and
      sponsors negotiate with increasingly empowered local communities and host
      countries to achieve meaningful and substantive benefits from biomedical research
      for all stakeholders.

PMID- 19385754
TI  - Sharing data and results with study participants: report on a survey of cultural
      anthropologists.
AB  - A FIRST-EVER SURVEY of cultural anthropologists was conducted concerning the
      sharing of data, interpretations, and results with study participants. Briefly
      summarized, the study showed that almost all of the survey respondents had shared
      data or results with participants and almost all found this to be a positive
      experience. They had carried out research in many countries, some over long
      periods of time, and many had completed several field projects. Most believe that
      researchers, either alone or in consultation with participants and their groups,
      should decide whether, when, and what to share. Anthropologists find that sharing
      produces many benefits, for themselves as individuals and as researchers, for
      individual participants, and for the communities, groups, or institutions to
      which the latter belong. The perceived harms that might result from sharing have
      to do particularly with potential threats to privacy, confidentiality or
      anonymity, as well as the possibilities of social conflict and oppression. Thus,
      researchers have serious concerns about the sharing of certain kinds of data that
      might lead to such consequences. While many or most respondents think that
      sharing is the ethically proper course of action, they are very aware of the
      complexities of particular situations and the need for nuanced decision making.
      Most think that the researcher should play a major role in deciding whether
      sharing should take place and what should be shared. Hence, for these cultural
      anthropologists, in the end, sharing requires trying to balance the good of
      sharing with the good of doing no harm to those with whom they have done
      research.

PMID- 19385755
TI  - Trust in health research relationships: accounts of human subjects.
AB  - TRUST IS FUNDAMENTAL in health research, yet there is little empirical evidence
      that explores the meaning of trust from the perspective of human subjects. The
      analysis presented here focuses on how human subjects talked about trust in the
      in-depth interviews. It emerged from the accounts that trust could not be assumed
      in the research setting, rather it was portrayed as a dynamic concept, built and
      easily broken, characterized by reciprocity and negotiation. Human subjects were
      ambivalent about who, when, what, and how much to trust in the research endeavor.
      This paper adds a fresh perspective to the literature on trust, and so offers a
      currently neglected, and little understood dimension to the discourse around
      health research ethics.

PMID- 19385756
TI  - International analysis of institutional review boards registered with the u.s.
      Office for human research protections.
AB  - INSTITUTIONAL REVIEW BOARDS form the backbone of the human subject protection
      system. Yet little is known about the characteristics of these committees. This
      study compiles and analyzes the data on 1,326 IRBs in 113 countries registered
      with the Office for Human Research Protections. The study analyzes data on the
      following IRB characteristics: institutional affiliation, number of full-time
      administrative positions, approximate total number of protocols, and number of
      currently active protocols supported by DHHS or regulated by the Food and Drug
      Administration. The analysis found that the most common IRB profile is to be
      affiliated with a clinical organization (41.9% of IRBs) and to have one full-time
      staff member (40.0%). Regarding protocol volume, the most common IRB profile was
      to have 26-99 currently active protocols (42.0% of IRBs), to have 1-25 DHHS
      protocols (46.6%), and 1-25 FDA-regulated protocols (45.6%). Further analyses
      reveal considerable differences among countries. This study can provide a
      baseline for future IRB evaluations.

PMID- 19385757
TI  - The convergence of research and clinical practice: institutional review board
      review of humanitarian use device applications.
AB  - WE SURVEYED IRB CHAIRS IN THE United States to ascertain whether their IRBs have
      clarity regarding their FDA-mandated role in reviewing humanitarian use device
      (HUD) applications, which are neither research devices nor fully tested
      treatments. Of 2,588 Chairs, 469 (18%) completed the survey, almost half of whom
      (44%) reported review of a HUD application within the previous five years.
      Findings suggest that many IRB Chairs are confused about what HUDs are, how to
      review HUD applications, and why IRBs should review them. We recommend that the
      FDA clarify their policies so that Chairs can provide the guidance necessary for
      IRBs to more effectively and consistently review HUD applications, and thereby
      better protect HUD-treated patients.

PMID- 19385758
TI  - IRB Chairs' Perspectives on Genomics Research Involving Stored Biological
      Materials: Ethical Concerns and Proposed Solutions.
AB  - WE EVALUATED 55 IRB CHAIRS' perspectives on ethical issues in a hypothetical
      study involving mental health-related genomics research using stored specimens to
      identify potential barriers and solutions to such research. Most Chairs
      identified the ethical issues of consent and confidentially as important. The
      majority of Chairs expressed concern about using materials in new research,
      especially concerning a mental health condition, that was not discussed in the
      original consent. Few Chairs considered permissible strategies, such as
      deidentification and waiver of consent, which could allow the proposed research
      to go forward without consent. Chairs who reviewed more protocols and had
      attended conferences on human subjects protection identified more of the salient
      ethical issues in the scenario. Our study could not determine whether Chairs were
      not familiar with the strategies of de-identification and waiver of consent, or
      believed that they did not adequately protect participants who had provided
      specimens for research. Thus, our findings suggest that investigators and IRBs
      should consider future use of specimens and obtain appropriate consent before
      collection of specimens. Furthermore, our findings suggest that IRBs can improve
      review of genomics research involving stored specimens by redesigning forms to
      prompt IRB members to consider some strategies, such as de-identification and
      Certificates of Confidentiality, that are recommended for this type of research
      and by sending members to conferences on human subjects protections and research
      ethics.

PMID- 19385759
TI  - Educational advantage.
AB  - This issue of JERHRE introduces a concept vital to successful research-trust-and
      shows that it can be variously earned and destroyed. An understanding of these
      aspects of trust and reflection on how they pertain to new instances of research
      can be of great value to students, professionals, and those who review the
      research of others. Also described in this issue are various aspects of the
      structure and process of ethics committees that have an important impact on the
      quality of their performance, and merit the attention of research administrators
      and ethics committee members. Last, but not least, the U.S. Bureau of Census has
      made available to the public its training module on confidentiality; this, in
      conjunction with other resources, can provide useful tutorials for investigators
      and ethics committee members.

PMID- 19385760
TI  - Research agenda.
AB  - This issue of JERHRE focuses on two topics that have been largely ignored-trust
      in the human research industry and structural factors that affect the efficacy of
      ethical review of human research (i.e., factors that are not under the control of
      ethics committee members, such as the funding of committee resources and the
      provision of clear workable regulations). Trust and an adequate ethical
      infrastructure are integral to one another. Ethical capacity does not reside with
      an ethics committee alone, but springs from four foundations of ethical research.
      It derives from (a) national bodies that regulate research and clarify the
      ethical principles that are promulgated, (b) the institutional research
      administrations that finance and build the needed infrastructure, (c) the ethics
      committees that struggle to operate within this system, and (d) the individual
      disciplines and departments that should work collaboratively with investigators
      and ethics committees to provide needed expertise. Research on trust and adequate
      ethical review needs to be mindful of the larger dynamic system within which
      ethical oversight occurs, and how failure of any of its four major components
      weakens its other components.

PMID- 19385764
TI  - Data mining: knowledge discovery for human research ethics.

PMID- 19385765
TI  - Hidden data for research ethicists: an introduction to the concept and a series
      of papers.
AB  - THIS SPECIAL SECTION OF THE Journal of Empirical Research on Human Research
      Ethics (JERHRE) is based upon the assumption that much of the best empirical data
      relevant to research ethics is hidden from the view of Research Ethics Committee
      (REC) members and others who are interested in research ethics. There are at
      least three different senses in which ethics-relevant empirical research may be
      hidden: (1) it may be published in a journal that ethics committee members would
      not regularly read, (2) it may not use key words that would guide one to its
      ethics-relevant content, or (3) it may be sequestered in part of a research
      article that is about something else. This special section of JERHRE reviews all
      of these types of "hidden ethics" articles on the following issues: What is the
      relative frequency of hidden ethics articles in journals that focus on vulnerable
      populations? What does the non-ethics literature in clinical research and
      experimental economic decision theory teach us about ways of improving subjects'
      comprehension of risk information? How satisfied are parents and children with
      their experience with pediatric psychotrophic medication trials? And, how can
      retention rates be improved in longitudinal studies of difficult regimens such as
      drug rehabilitation? There is a major amount of ethics-relevant literature that
      is hidden. Without better ways of communicating the existence of this literature
      through use of key words, or recasting of the information to highlight its
      relevance to research ethics in journals that ethics committee members read, the
      benefits of evidence-based ethical problem solving will be lost.

PMID- 19385766
TI  - Hidden Empirical Research Ethics: A Review of Three Health Journals from 2005
      through 2006.
AB  - WE HYPOTHESIZED THAT A SIGNIFICANT amount of empirical data pertinent to research
      ethics is currently inaccessible to research ethics committee or Institutuional
      Review Board (IRB) members for at least three reasons: it is published in non
      ethics journals; articles are not adequately indexed using ethics-related
      keywords; and articles do not discuss the ethical significance of their data. We
      reviewed all articles from three health journals from January 2005 to December
      2006, and identified 26 articles that contained data pertinent to research
      ethics. Only 7 articles contained keywords clearly related to research ethics; 15
      of the articles contained no discussion of the ethical significance of their
      findings. Overall the articles we found constituted 2.2% of the research articles
      published in the three journals during the two-year period. If the same average
      number of articles were extrapolated to the top 100 of the approximately 5,000
      journals indexed in MEDLINE, then at least 433 hidden ethics articles would be
      published each year. We conclude that better indexing of articles is needed, that
      IRB members and researchers need training to identify relevant data in the
      literature, and that IRB composition should include members from diverse
      disciplines familiar with ethics-relevant empirical data in their respective
      disciplines.

PMID- 19385767
TI  - Enrolling, Retaining, and Benefiting Out-of-Treatment Drug Users in Intervention
      Research.
AB  - LONGITUDINAL RESEARCH ON street-recruited out-of-treatment drug users involves
      ethical issues concerning enrollment and retention of participants, remuneration
      and benefits. In contrast to practices of excluding such high-risk populations
      from research and assuming that they would not comply with a protocol requiring
      repeated measures over a 12-month period, this report presents examples from 15
      years of community-based studies that have enrolled drug-using participants and
      achieved a 96% retention rate. We also examine ethical issues connected with cash
      remuneration, and describe methods to elucidate the kinds of benefits that are
      most meaningful to this population. Findings suggest that the research community
      must reconsider the ethics of blanket exclusions of such high-risk subjects, and
      make evidence-based decisions about recruitment, retention, remuneration, and
      benefits.

PMID- 19385768
TI  - Assessing and improving research participants' understanding of risk: potential
      lessons from the literature on physician-patient risk communication.
AB  - EVIDENCE THAT LAY PEOPLE FREQUENTLY misinterpret risk raises concerns for the
      ethical conduct of human research, which requires adequate disclosure,
      understanding, and appreciation of risk information. Review of the risk
      communication research literature suggests new directions for empirical research
      on human research ethics: Investigation is needed on how to best assess and
      improve potential and enrolled subjects' understanding of risk information.
      Preferences regarding the presentation of risk information and the effects of
      alternative presentation formats and decision aids on knowledge, trust,
      satisfaction, risk/benefit analysis, and perceptions of respectful treatment
      should be studied. Research is also needed on the effects of payment for research
      participation, the order in which study information is presented, and having
      one's own physician present risk information.

PMID- 19385769
TI  - Psychotropic medication research in children and adolescents: empirical findings
      and ethical implications.
AB  - WITH THE ESCALATION IN PRESCRIPTIONS of psychotropic medicine to young people
      over the last 11.2 decades, there has been increased scrutiny of
      psychopharmacological research with children and adults. There is a small but
      growing literature on participant knowledge of consent form information and of
      subject satisfaction in psychopharmacological studies. The data thus far suggest
      that parents and their participating children generally have had a good knowledge
      of the purposes of the trials, experimental conditions, possibility of receiving
      placebo, and right to withdraw from pharmacological trials; however,
      understanding of randomization is relatively poor. Social validity surveys
      indicate high levels of satisfaction with choice of outcome measures, clinical
      recommendations emanating from the research, and treatment received; most
      participants indicate that they would recommend the studies to other parents and
      children having similar conditions. None of the studies reviewed appears in a
      journal dedicated to research ethics or bioethics and in this sense may be hidden
      from IRB members and bioethicists. Nevertheless, the findings are pertinent to
      IRB deliberations. More research on participant knowledge and satisfaction is
      needed, with some emphasis on the perspectives of the youth themselves.

PMID- 19385770
TI  - Do incentives exert undue influence on survey participation? Experimental
      evidence.
AB  - MONETARY INCENTIVES ARE INCREASINGLY used to help motivate survey participation.
      Research Ethics Committees have begun to ask whether, and under what conditions,
      the use of monetary incentives to induce participation might be coercive. The
      article reports research from an online vignette-based study bearing on this
      question, concluding that at present the evidence suggests that larger incentives
      do not induce research participants to accept higher risks than they would be
      unwilling to accept with smaller ones.

PMID- 19385771
TI  - Purpose and benefits of early phase cancer trials: what do oncologists say? What
      do patients hear?
AB  - CANCER PATIENTS OVERESTIMATE BENEFITS of early phase trials but studies have not
      reported what oncologists say to patients about trials. We audiotaped oncologists
      talking to cancer patients about Phase I or II trials and interviewed patients
      about the purpose and expected outcomes of trials presented to them. Oncologists
      gave mixed messages, saying Phase I trials measure safety and dosing, yet
      referring to trials as treatment with uncertain therapeutic effects. Seventeen
      percent of Phase I respondents said the trial's purpose related to safety/dosing
      (p = 0.017); 17% of Phase I respondents said the purpose was "to cure my cancer."
      Patients may find it important to believe trials offer significant benefit.
      Oncologists, while respecting patients' hopes, should be precise in their
      language, particularly regarding Phase I trials, distinguishing early stages of
      research from treatment.

PMID- 19385772
TI  - Educational advantage.
AB  - THIS ISSUE OF JERHRE features three main themes: (1) finding and using empirical
      research bearing on ethical problem-solving that does not appear in the ethics
      related literature; (2) determining whether large incentives can induce subjects
      to accept risks that they otherwise would consider unacceptable, and (3)
      examining some of the complexity and uncertainty surrounding subjects' decisions
      to participate in research. Each of these articles breaks important new
      conceptual and methodological ground and provides new venues for evidence-based
      ethical problem-solving. A thoughtful grasp of these new concepts will provide
      new tools and opportunities for students, investigators, and ethics committees.

PMID- 19385773
TI  - Research agenda.
AB  - THIS ISSUE OF JERHRE introduces the concept of hidden ethics---empirical data
      relevant to ethical problem-solving that does not appear in the ethics literature
      and is difficult to access. Three related research agendas are suggested
      concerning methods of finding this literature, scope of inquiry, and synthesis of
      new knowledge about ethical problem-solving. This issue also introduces the
      complexities and uncertainties that face persons when deciding whether to
      participate in Phase 1 and Phase 2 trials. Finally, it introduces a rigorous
      statistical approach to determining whether an incentive can be large enough to
      influence subjects to take risks they ordinarily would not take, and thus sets as
      a research agenda the further exploration of the generalizability of this method
      and the current findings.

PMID- 19385777
TI  - Protecting the Vulnerable: Who are They?

PMID- 19385778
TI  - Opinions of IRB Members and Chairs Regarding Investigators' Relationships with
      Industry.
AB  - THE EFFECTS OF CONFLICTS OF INTEREST on the conduct of human research have been
      roundly debated, but less attention has been paid to the role of Institutional
      Review Boards (IRBs) in their identification and management. Government and
      private policy recommendations disagree about IRBs' responsibility in this area.
      A survey focusing on respondents' attitudes and behaviors regarding consideration
      of investigator and institutional financial relationships with industry when
      reviewing research protocols was mailed to a random sample of 893 IRB members and
      316 IRB chairs at 115 academic institutions (response rates of 67% and 72%,
      respectively). More than half of IRB members and chairs felt that industry
      relationships posed a moderate or big problem for research integrity nationally,
      and about one-third thought such relationships were a problem at their own
      institution. Approximately two-thirds felt that investigator-industry
      relationships should be considered when reviewing protocols regardless of whether
      they are deemed to be conflicts of interest. While more than 90% of IRB members
      and chairs believed that investigators' relationships should be disclosed to
      research participants, 61% of members and chairs reported that these
      relationships were not always disclosed to participants. While more than 80%
      believed that institutional relationships should be disclosed to research
      participants, only 39% of members and chairs said this happened all the time.
      Some beliefs of IRB members and chairs are at odds with recommendations to limit
      the role of IRBs in the management of potential investigator conflicts. Lack of
      unambiguous guidelines has led to inconsistent practices among IRBs.

PMID- 19385779
TI  - IRB Member Judgments of Decisional Capacity, Coercion, and Risk in Medical and
      Psychiatric Studies.
AB  - WHILE INDIVIDUALS WITH PSYCHIATRIC illnesses are widely considered a special
      class of research subjects regarding decisional capacity and coercion
      vulnerability, those with physical illnesses often are not. IRB members (N = 127)
      read vignettes that described clinical research targeting one of two levels of
      disease severity (high/low) for psychiatric or medical diagnoses. They then rated
      decisional capacity, coercion, and risks for hypothetical research subjects. IRB
      members viewed psychiatric subjects as having greater vulnerability to coercion
      and less decisional capacity than medical subjects, even when medical illness was
      of a severity likely to engender psychiatric comorbidities. These results suggest
      that IRB members may inflate the vulnerability and decisional incapacity of
      psychiatric subjects, while discounting vulnerability and incapacity in medical
      subjects.

PMID- 19385780
TI  - Investigating Perceived Institutional Review Board Quality and Function Using the
      IRB Researcher Assessment Tool.
AB  - THE INSTITUTIONAL REVIEW BOARD-RESEARCHER ASSESSMENT TOOL (IRB-RAT) was designed
      to assess the relative importance of various factors to the effective functioning
      of IRBs. We employed the IRB-RAT to gain insight into the ways in which our IRB
      is perceived to be deficient by those who routinely interact with our Office of
      Research Integrity and Protections. Respondents ranked qualities thought to be
      characteristic of an "ideal" IRB and then compared our IRB to that internal
      standard. We observed that the rate of study participation varied by role. The
      composite relative ranking of the 45 items that comprise the IRB-RAT differed
      significantly from the rank order reported by Keith-Spiegel et al. Our data
      furthermore suggest that role influences scoring of the IRB-RAT (e.g.,
      investigators awarded our IRB significantly higher scores in several areas than
      did research coordinators). Additional research is warranted to determine if the
      observed role-dependent differences in the perceived quality of our IRB simply
      reflect the local research culture or if they are indicative of a more
      fundamental and generalizable difference in outlook between investigators and
      research coordinators.

PMID- 19385781
TI  - Perceived benefits in trauma research: examining methodological and individual
      difference factors in responses to research participation.
AB  - THIS STUDY EXAMINED METHODOLOGICAL and individual difference factors in relation
      to perceived benefits and cost-benefit ratios among adult participants in trauma
      related research. In two samples (N's = 72 and 118), ethnically-diverse community
      participants completed trauma-related questionnaires plus an in-depth interview.
      In separate community (N = 213) and undergraduate (N = 130) samples, participants
      completed trauma-related questionnaires, but no interviews. Participants rated
      their perceptions of the research process using the Response to Research
      Participation Questionnaire (RRPQ). Cost-benefit ratios were favorable in all
      samples. The research procedures (questionnaires only versus questionnaires plus
      interviews) explained unique variance in RRPQ scale scores and cost-benefit
      ratios, as did trauma-related distress. Implications of these findings for
      developing trauma research protocols are discussed.

PMID- 19385782
TI  - Children's Perception of Research Participation: Examining Trauma Exposure and
      Distress.
AB  - USING THE REACTIONS TO RESEARCH Participation Questionnaire for Children (RRPQ
      C), this study examined perceptions of research participation among 181 school
      aged children with and without trauma histories. As part of two larger studies,
      children completed non-trauma related tasks to assess emotion understanding and
      cognitive ability. Parents (and not children) reported on children's
      interpersonal (e.g., sexual abuse, physical abuse, witnessing domestic violence,
      witnessing community violence) and non-interpersonal (e.g., motor vehicle
      accidents, medical traumas, natural disasters) trauma exposure. Children's
      perceptions of costs and benefits of research participation and understanding of
      informed consent did not vary as a function of trauma exposure. The number of
      traumatic events experienced was unrelated to children's perceptions.
      Furthermore, children across trauma-exposure groups generally reported a positive
      cost-benefit ratio, and understanding of the consent information. Implications of
      these data are discussed.

PMID- 19385783
TI  - The effects of trauma-focused research on pregnant female participants.
AB  - RECENT EMPHASIS ON THE ETHICAL CONDUCT of researchers has resulted in a growing
      body of literature exploring the impact of trauma-focused research on
      participants. To date, pregnant women have not been widely included in trauma
      focused research, possibly because they are considered a vulnerable population in
      research. The current research investigated how 41 expectant mothers responded to
      participation in a trauma-focused study. Overall, the results of this study
      suggest that trauma-focused research is well tolerated by pregnant women.
      Specific findings indicated that pregnant women considered more traumatized
      perceived greater benefits from participation. Best practices for conducting
      ethical trauma-focused research with pregnant women are provided. As well,
      recommendations for future research are outlined in an effort to further extend
      the ethical understanding of the benefits and costs of trauma-focused research
      with potentially vulnerable populations.

PMID- 19385784
TI  - Administrators' perspectives on ethical issues in long-term care research.
AB  - ETHICAL ISSUES ARE A SIGNIFICANT potential barrier to much-needed research in
      long-term care settings. LTC stakeholder perspectives are largely absent from the
      development of regulation and guidelines. Fifteen long-term care administrators
      were interviewed as part of a study of ethical issues in community-based, long
      term care research. Established qualitative procedures for conducting content
      analysis were used to organize the data. Findings suggest that existing
      mechanisms to protect human subjects do not take into account important
      differences between academic and long-term care settings. The full potential of
      LTC research will not be realized until supportive processes to enhance human
      subjects protections are developed in a way that is reflective of the LTC
      environment.

PMID- 19385785
TI  - Public disclosure in research with exception from informed consent: the use of
      survey methods to assess its effectiveness.
AB  - IN CLINICAL TRIALS WITH EXCEPTION from informed consent, the Final Rule
      stipulates that investigators inform and consult with the community. A random
      digit-dialing survey of 200 individuals assessed the effectiveness of public
      disclosure via press releases, notices in local newspapers, local radio and
      television stations and the host hospital's website, as well as a series of
      community meetings regarding a pending clinical trial of this kind. Results
      showed a 10% awareness level of the public trial, which is higher than surveys
      using convenience samples. Understanding of the nature of the trial was generally
      poor, while opinions about participating in this type of research were more
      favorable among individuals aware of the trial. Our findings suggest that
      adherence to the intent of the Final Rule is dependent on uniform guidelines for
      what constitute effective public disclosure methods and adequate community
      awareness and understanding and the use of rigorous sampling methods for
      evaluation.

PMID- 19385786
TI  - Are We Misjudging How Well Informed Consent Forms are Read?
AB  - UNDERSTANDING THAT INFORMED CONSENT forms are provided to be read and
      comprehended, this study compares the research assistant's perception of
      comprehension with the actual time potential participants spend reading their
      consent form. After providing information verbally to two samples of women,
      research assistants observed as the women reviewed and signed the consent form
      recording the time spent reading and the assistant's impression of reading
      behavior. Over half of the women "read" their consent forms in thirty seconds or
      less before signing. Despite the brief time participants actually read, research
      assistants reported that 38%-74% (depending on the sample) appeared to have
      completely read the forms. Research to determine if timing aids will improve
      research assistants' assessment of participant reading behaviors should be
      considered.

PMID- 19385788
TI  - Research agenda.
AB  - THIS ISSUE OF JERHRE FOCUSES on various kinds of vulnerability: those of
      institutions due to poor detection of risk, and those of research participants
      who fall into subpopulations considered vulnerable. These problems suggest many
      fruitful forms of research that can advance understanding of ways to better
      protect human subjects, research activities, and institutions.

PMID- 19385787
TI  - Educational advantage.
AB  - THIS ISSUE OF JERHRE FEATURES themes of risk management at various levels within
      the research institution. At the institutional level, we see that many questions
      remain unanswered with regard to handling conflicts of interest, providing much
      opportunity for introspection about one's own institution. We also see that
      evaluation of IRB functioning is not uniform across sectors of the institution
      another important area for examination of one's own institution. Within research
      on risky topics, we find that empirical data do not bear out intuition-based
      predictions of risk providing an important rationale for empirical explorations
      of one's own subjects' evaluation of their own reactions to the research
      experience. Finally we focus on some typically silent partners in the research
      process: gatekeepers who are entrusted with some risk management
      responsibilities, and explore whether they fulfill their appointed roles
      adequately.

PMID- 19385791
TI  - Emerging ethical challenges in advanced neuroimaging research: review,
      recommendations and research agenda.
AB  - The dynamic and ever-evolving nature of neuroimaging research creates important
      ethical challenges. New domains of neuroscience research and improving
      technological capabilities in neuroimaging have expanded the scope of studies
      that probe the biology of the social and ethical brain, the range of eligible
      volunteers for research, and the extent of academic-industry relationships.
      Accordingly, challenges in informed consent and subject protection are surfacing.
      In this context, we provide an overview of the current landscape for neuroimaging
      and discuss specific research ethics topics arising from it. We suggest
      preliminary approaches to tackle current issues, and identify areas for further
      collaboration between neuroimagers and institutional review boards (research
      ethics committee).

PMID- 19385792
TI  - Empirically Assessing Participant Perceptions of the Research Experience in a
      Randomized Clinical Trial: The Women's Self-Defense Project as a Case Example.
AB  - A growing body of empirical literature has systematically documented the
      reactions to research participation among participants in traumafocused research.
      To date, the available data has generally presented an optimistic picture
      regarding participants' ability to tolerate and even find benefit from their
      participation. However, this literature has been largely limited to cross
      sectional designs. No extant literature has yet examined the perceptions of
      participants with psychiatric illness who are participating in randomized
      clinical trials (RCTs) designed to evaluate the efficacy or effectiveness of
      novel trauma treatments. The authors posit that negative experiences of, or poor
      reactions to, the research experience in the context of a trauma-focused RCT may
      elevate the risk of participation. Indeed, negative reactions may threaten to
      undermine the potential therapeutic gains of participants and promoting early
      drop out from the trial. Empirically assessing reactions to research
      participation at the pilot-study phase of a clinical trial can both provide
      investigators and IRB members alike with empirical evidence of some likely risks
      of participation. In turn, this information can be used to help shape the design
      and recruitment methodology of the full-scale trial. Using data from the pilot
      study of the Women's Self-Defense Project as a case illustration, we provide
      readers with concrete suggestions for empirically assessing participants'
      perceptions of risk involved in their participation in behaviorally oriented
      clinical trials.

PMID- 19385793
TI  - Research Ethics Review and Aboriginal Community Values: Can the Two be
      Reconciled?
AB  - CONTEMPORARY RESEARCH ETHICS REVIEW COMMITTEES (RECs) are heavily influenced by
      the established academic or health care institutional frameworks in which they
      operate, sharing a cultural, methodological and ethical perspective on the
      conduct of research involving humans. The principle of autonomous choice carries
      great weight in what is a highly individualistic decision-making process in
      medical practice and research. This assumes that the best protection lies in the
      ability of patients or research participants to make competent, voluntary,
      informed choices, evaluating the risks and benefits from a personal perspective.
      Over the past two decades, North American and international indigenous
      researchers, policy makers and communities have identified key issues of
      relevance to them, but ignored by most institutional or university-based RECs.
      They critique the current research review structure, and propose changes on a
      variety of levels in an attempt to develop more community sensitive research
      ethics review processes. In doing so, they have emphasized recognition of
      collective rights including community consent. Critics see alternative policy
      guidelines and community-based review bodies as challenging the current system of
      ethics review. Some view them as reflecting a fundamental difference in values.
      In this paper, we explore these developments in the context of the political,
      legal and ethical frameworks that have informed REC review. We examine the
      process and content of these frameworks and ask how this contrasts with emerging
      Aboriginal proposals for community-based research ethics review. We follow this
      with recommendations on how current REC review models might accommodate the
      requirements of both communities and RECs.

PMID- 19385794
TI  - Applying research ethics guidelines: the view from a sub-saharan research ethics
      committee.
AB  - CONSIDERABLE VARIATION HAS BEEN demonstrated in applying regulations across
      research ethics committees (RECs) in the U.S., U.K., and European nations. With
      the rise of international research collaborations, RECs in developing countries
      apply a variety of international regulations. We conducted a qualitative
      descriptive pilot study with members of the national REC in Malawi to determine
      criteria they use to review research, and their views on international
      collaborations. Qualitative content analysis demonstrated that international
      guidelines are interpreted in light of local African conditions such that
      emphasis is placed on examining benefit to the community and ensuring the
      informed consent process translates concepts in locally-meaningful ways. Members
      suggest that RECs often must comply with regulations that do not fit local
      conditions. Recommendations are provided for improving such international
      collaborations.

PMID- 19385795
TI  - Recommending randomized trials for pediatric leukemia: observer and physician
      report of recommendations.
AB  - Physicians' presentation of treatment options in a non-coercive manner is
      critical for informed consent for participation in randomized clinical trials
      (RCTs). This study examined discrepancies between observer and physician report
      of treatment recommendations for pediatric leukemia RCTs. This study also
      assessed relationships between recommendations and decisions to participate in
      RCTs. Participants were 104 parents of children with leukemia and the treating
      physicians. Measures included observations of informed consent conferences
      (ICCs), physician report of treatment recommendations, and parent report of trial
      participation. Observation revealed that physicians recommended RCTs in 38% of
      ICCs, while physicians reported recommending RCTs in 73% of ICCs. Treatment
      recommendations were unrelated to decisions to participate in RCTs. Results
      highlight the importance of enhancing parent-physician communication regarding
      RCT participation.

PMID- 19385796
TI  - Reported Goals For Knowledge to be Learned in Responsible Conduct of Research
      Courses.
AB  - EDUCATION IN RESPONSIBLE CONDUCT OF RESEARCH (RCR) has been a required part of
      training for students on U. S. National Institutes of Health (NIH) training
      grants for over 15 years. However, there is little evidence of commonly accepted
      goals for RCR instruction, making it difficult to assess effectiveness. As part
      of a larger study examining RCR instructors' goals for RCR education, this report
      focuses on those reported goals categorized as knowledge. To identify RCR
      instructors, e-mail requests were sent to the 116 recipients of NIH training
      grants awarded in 2000. Of 67 verified RCR instructors, 50 (75% response rate)
      from 37 different institutions were successfully interviewed. Despite a shared
      sense of the basics to be taught in RCR courses, these instructors were diverse
      in their views and understanding of goals for RCR education. This diversity
      suggests a challenge to be overcome not only for improving the effectiveness of
      RCR education, but also for attempts to assess that effectiveness.

PMID- 19385797
TI  - Research agendas.

PMID- 19385798
TI  - Educational advantage.
AB  - THE JUNE ISSUE OF JERHRE features three themes: (1) Managing risks or
      unanticipated events that arise in research and pose serious ethical and
      practical questions. (2) Collaborating across cultures when relevant values are
      not shared, in particular values of individualism found largely in Western
      cultures versus community values which are more frequently found in traditional
      cultures. (3) Challenges to researchers and their mentors of learning and
      teaching how to responsibly resolve or ameliorate difficult ethical challenges.

PMID- 19385803
TI  - Institutional introspection.

PMID- 19385804
TI  - Normative dissonance in science: results from a national survey of u.s.
      Scientists.
AB  - NORMS OF BEHAVIOR IN SCIENTIFIC RESEARCH represent ideals to which most
      scientists subscribe. Our analysis of the extent of dissonance between these
      widely espoused ideals and scientists' perceptions of their own and others'
      behavior is based on survey responses from 3,247 mid- and early-career scientists
      who had research funding from the U.S. National Institutes of Health. We found
      substantial normative dissonance, particularly between espoused ideals and
      respondents' perceptions of other scientists' typical behavior. Also, respondents
      on average saw other scientists' behavior as more counternormative than
      normative. Scientists' views of their fields as cooperative or competitive were
      associated with their normative perspectives, with competitive fields showing
      more counternormative behavior. The high levels of normative dissonance
      documented here represent a persistent source of stress in science.

PMID- 19385805
TI  - Personality and ethical decision-making in research: the role of perceptions of
      self and others.
AB  - THIS STUDY EXAMINED BASIC PERSONALITY characteristics, narcissism, and cynicism
      as predictors of ethical decision-making among graduate students training for
      careers in the sciences. Participants completed individual difference measures
      along with a scenario-based ethical decision-making measure that captures the
      complex, multifaceted nature of ethical decision-making in scientific research.
      The results revealed that narcissism and cynicism (individual differences
      influencing self-perceptions and perceptions of others) showed consistently
      negative relationships with aspects of ethical decision-making, whereas more
      basic personality characteristics (e.g., conscientiousness, agreeableness) were
      less consistent and weaker. Further analyses examined the relationship of
      personality to metacognitive reasoning strategies and socialbehavioral response
      patterns thought to underlie ethical decision-making. The findings indicated that
      personality was associated with many of these social-cognitive mechanisms which
      might, in part, explain the association between personality and ethical
      decisions.

PMID- 19385806
TI  - Content Validation of the Organizational Climate for Research Integrity (OCRI)
      Survey.
AB  - THE PURPOSE OF THIS STUDY WAS TO develop and establish content validity of an
      instrument designed to measure the organizational climate for research integrity
      in academic health centers. Twenty-seven research integrity scholars and
      administrators evaluated 64 survey items for relevance and clarity, as well as
      overall comprehensiveness of the constructs that are measured (organizational
      inputs, structures, processes and outcomes). Both quantitative and qualitative
      methods were used, particularly content validity indices (CVI) and analyses of
      respondents' comments. The content validity index for the overall survey was
      initially high (CVI = .83) and improved (CVI = .90) when 17 marginal-to-poor
      items were removed. This study resulted in the Organizational Climate for
      Research Integrity (OCRI) survey, a 43-item fixed-response survey with
      established content validity.

PMID- 19385807
TI  - Research Participants' Perceptions of the Certificate of Confidentiality's
      Assurances and Limitations.
AB  - THE CERTIFICATE OF CONFIDENTIALITY (COC) provides additional protections to
      personal and sensitive research data. COC guarantees are not absolute and
      investigators are obligated to inform potential participants of COC limitations.
      The present study utilized qualitative and partnership methodology to examine
      participants' (N = 24) perceptions of COC assurances and limitations in the
      context of a hypothetical study on depression. Although some participants were
      comforted by COC assurances, a majority of participants had
      confidentiality/privacy concerns specifically with COC passages concerning
      federal audits and legal reporting requirements. As one respondent noted, "Why is
      it that you guys don't have to turn the records over to the court unless I say so
      . . . but you have to give them over to the government? . . . I don't know about
      what is goin' on." Our findings underscore the need for larger quantitative
      investigations to examine the negative and positive impact of COCs on research
      participation and response bias.

PMID- 19385808
TI  - The reporting of monetary compensation in research articles.
AB  - STUDY PARTICIPANT COMPENSATION IS OF increasing concern, yet few investigations
      have explored it; none have examined whether published journal articles report
      it. Medline searches for articles in six areas-HIV, substance abuse (heroin and
      cocaine), depression, essential hypertension, and cardiac surgery-reveal very low
      mention of payment (0-32.1%). Of 207 articles, only 13.5% mentioned financial
      compensation in any way, and only 11.1% listed amounts. Of the 207 studies, 92
      involved more than minimal risk interventions, but were not more likely to
      mention compensation. Studies that included substance users were significantly
      more likely than others to mention payment (p < .001). These overall low rates
      are concerning as they can hamper evaluation of ethical issues, and impact study
      replicability. Publication requirements should consider discussion of
      compensation.

PMID- 19385809
TI  - Education level, primary language, and comprehension of the informed consent
      process.
AB  - TO OBTAIN INFORMATION ON HOW PERSONS from diverse backgrounds experience the
      informed consent process, we surveyed adults with a wide variety of educational
      levels and different primary languages (English, Spanish, or Vietnamese) who had
      recently enrolled in a study requiring written informed consent. Of the 100
      participants, 62 were non-White, 43 had less than a high school education, and 60
      had a primary language other than English. The median score for comprehension was
      62% (IQR 50-76%); the median satisfaction score was 86% (IQR 71-100%). In
      multivariate analysis, only educational level was significantly associated with
      comprehension and satisfaction with the informed consent process (p < 0.001).
      Comprehension and satisfaction with the informed consent process were markedly
      lower among persons with lower educational levels.

PMID- 19385810
TI  - The impact of minor adverse event tracking on subject safety: a web-based system.
AB  - BASED ON THE ASSUMPTION THAT MINOR symptoms may presage serious events, we report
      four years' experience with a web-based adverse event (AE) tracking system
      (eAETS) designed to capture AEs of a minor nature that would not meet criteria
      for ethical review. The eAETS has supported 175 diverse clinical protocols, is
      user-friendly and navigationally intuitive, and restricts access based on
      protocol ownership. The user creates an initial risk profile for comparison to
      subsequent AEs to identify unanticipated patterns. Out of 2,440 AE reports, 1,053
      did not match the risk profile. Corrective modification was recommended in 6
      (13%) protocols. The eAETS provides a framework for weighing the impact of AEs on
      subject safety.

PMID- 19385811
TI  - Guide to researching human research subjects laws in west Africa.
AB  - BECAUSE OF THE SCARCITY OF PUBLICLY accessible information on West African human
      research subjects' protections, resources are difficult to find; many of these
      nations do not have local laws governing human research subjects protections and
      many of the local regulations are not available online. Without such information,
      investigators cannot effectively develop acceptable methods and procedures as
      they plan research in West African countries. This guide is intended for research
      ethics committee administrators, governmental and commercial regulators,
      ethicists, those in the legal community, and researchers seeking information
      regarding human research subjects' protections laws in West Africa. It is
      assembled in the hope that it will make these resources more widely available and
      so aid in the review and conduct of research involving human research subjects
      and stimulate further efforts to update such information as new regulations
      evolve.

PMID- 19385812
TI  - Educational advantage.
AB  - THIS ISSUE OF JERHRE FEATURES ARTICLES on characteristics of persons and
      institutions that influence whether research is conducted in an ethically
      responsible manner. As such, these articles provide investigators, ethics
      committees and research administrators with tools for informal self-assessment
      and training.

PMID- 19385816
TI  - Empirical research to evaluate ethics committees' burdensome and perhaps
      unproductive policies and practices: a proposal.
AB  - THE U.S. SYSTEM FOR THE PROTECTION of human research subjects, particularly its
      ethics committee or Institutional Review Board (IRB) component, is excessively
      burdened. Many commentators, myself included, are concerned that, as a
      consequence of these excessive burdens, the IRB is losing its effectiveness in
      safeguarding the rights and welfare of human subjects. I believe that IRBs devote
      too much time doing work that simply does not need to be done. Several routine
      practices of IRBs are highly time consuming and, in my opinion, not sufficiently
      productive to warrant their continuation in their present form. Empirical
      research can and should be done to evaluate the consequences of these practices.
      If they are found to be insufficiently cost-effective, they should be modified or
      abandoned. This would result in reducing the burdens on IRBs, freeing up
      reviewers' time and energy to concentrate on more important and productive
      pursuits. I suggest we begin by evaluating two routine practices: (1) The
      practice of conducting all continuing reviews of ongoing research at convened
      meetings of the IRB. (2) The practice of referring all adverse events to the IRB
      for its review.

PMID- 19385818
TI  - Research agenda.

PMID- 19385817
TI  - Educational advantage.
AB  - The September Issue of Jerhre Features four themes: Experiments that IRBs might
      conduct to evaluate alternative candidates for best IRB practices; Ways of
      learning and respecting the values of research participants, with special focus
      on participants from traditional cultures; Evidence-based assessment of the
      emotional risk inherent in research on trauma and other kinds of research that
      may produce an emotional response; and Procedures for sharing data and solving
      problems of disclosure risk while retaining analytical usefulness of the data.
      The curriculum materials presented here are deliberately general so that the
      instructor can adapt them to any students, be they freshmen, ethics committee
      members, or senior investigators. Drawing on the concepts and methods presented
      in the seven articles that explore these four topics, some useful skills of
      ethical problem solving can be developed.

PMID- 19385819
TI  - Women's Autonomy and Informed Consent in Microbicides Clinical Trials.
AB  - ACHIEVING RESPECT FOR PERSONS is problematic in settings with concepts of
      autonomy that differ from Western values. For international research, women's
      autonomy to consent to participation is an increasingly contentious issue. We
      present data from ancillary studies conducted in preparation for a clinical trial
      testing the safety and efficacy of topical microbicides, used to prevent HIV
      infection. These ancillary studies were conducted in seven countries, using
      qualitative research methods to collect data from female and male community
      members, and their health care professionals and community leaders. Our findings
      indicate that by working at the level of the community, couple and individual,
      researchers may be able to take steps to increase women's ability to make their
      own independent decisions about participating in research. This approach may, in
      turn, improve both the conduct and outcomes of research.

PMID- 19385820
TI  - The importance of story-telling: research protocols in aboriginal communities.
AB  - AN ORAL TRADITION AND STORY TELLING CULTURE are still central to aboriginal
      personal and community identity, and provide major means of remembering and
      conveying personal and community experience with university researchers. These
      stories describe stark accounts of betrayal and upset, as well as descriptions of
      positive experiences. They provide dramatic reminders to researchers of the
      importance of respectful and collaborative relationships with traditional
      community leaders and their members.

PMID- 19385821
TI  - Ethical issues in trauma-related research: a review.
AB  - ETHICAL DECISION-MAKING ABOUT TRAUMA-RELATED STUDIES requires a flexible
      approach that counters assumptions and biases about victims, assures a favorable
      ethical cost-benefit ratio, and promotes advancement of knowledge that can
      benefit survivors of traumatic stress. This paper reviews several ethical issues
      in the field of traumatic stress: benefit and risks in trauma-related research,
      whether trauma-related research poses unique risks and if so what those might be,
      informed consent and mandatory reporting, and supervision of trauma-related
      research. For each topic, we review potential ethical issues, summarize the
      research conducted thus far to inform ethical practice, and recommend future
      practice, research questions and policies to advance the field so that research
      on trauma can continue to be a win-win situation for all stakeholders in the
      research enterprise.

PMID- 19385822
TI  - Introduction: data sharing and disclosure limitation techniques.
AB  - THIS SPECIAL SECTION OF JERHRE is in response to the needs of institutions to
      develop advanced data sharing capabilities. On October 1, 2003, the National
      Institutes of Health (NIH) initiated a requirement that investigator-initiated
      proposals for grants with direct costs over $500,000 in any year incorporate
      plans to accommodate sharing research data. The requirement stipulates that such
      plans describe the procedures through which shared data would be rendered "free
      of identifiers that would permit linkages to individual research participants and
      variables that could lead to deductive disclosure of the identity of individual
      subjects." (http://grants2.nih.gov/grants/policy/data_sharing). We expect that
      many researchers who deal with human research data are unfamiliar with the
      procedures presented in the ensuing articles. These sophisticated procedures have
      been developed to help protect confidentiality of subjects' data in files that
      are shared, while simultaneously preserving the analytic value of data for
      secondary users. Among these are procedures developed by government statisticians
      that include innovative methods to prevent deductive disclosure of identities.
      More recently, academic researchers and data experts have adapted or extended
      these methods. Together, these methods aim to achieve both disclosure limitation
      and retention of key analytic usefulness of the shared data.

PMID- 19385823
TI  - Essentials of the disclosure review process: a federal perspective.
AB  - MANY RESEARCHERS NEED TO MAKE arrangements to share de-identified electronic
      data files. However, the ways in which respondent identity may be protected are
      not well understood or are assumed to be the special province of large
      statistical agencies or specialized statisticians. Approaches to data sharing and
      protecting respondent identity have been pioneered by federal agencies which
      gather data vital to political and economic decision making. These agencies are
      required by statutory law both to assure confidentiality and to share data in
      usable form with other governmental agencies and with scholars who perform needed
      analyses of those data. The basic principles of disclosure limitation developed
      by the Census Bureau, the National Center for Health Statistics, and other
      federal agencies are fundamental to meeting new funding requirements to share and
      deidentify data, and are often referred to in the literature on data sharing. We
      describe how these principles are employed by the Disclosure Review Boards (DRBs)
      of these two agencies, and then state these principles in more general terms that
      are applicable to any disclosure review process. The kinds of data that academic
      institutions share may call for less complex or stringent DRBs and specific
      nondisclosure procedures different from those employed by federal agencies, but
      the same general principles apply. Specific application of these six principles
      by non-government researchers will depend on the nature of their data, their own
      institutional resources, and the likely future usefulness of their data.

PMID- 19385824
TI  - Solving problems of disclosure risk while retaining key analytic uses of publicly
      released microdata.
AB  - MEASURES USED TO PROTECT SUBJECTS in publicly distributed microdata files often
      have a significant negative impact on key analytic uses of the data. For example,
      it may be important to analyze subpopulations within a data file such as racial
      minorities, yet these subjects may present the greatest disclosure risk because
      their records tend to stand out or be unique. Files or records that are linkable
      create another type of disclosure risk-common elements between two files can be
      used to link files with sensitive data to externally available files that
      disclose identity. Examples of disclosure limitation methods used to address
      these types of issues include blanking out data, coarsening response categories,
      or withholding data altogether. However, the very detail that creates the
      greatest risk also provides insight into differences that are of greatest
      interest to analysts. Restricted-use agreements that provide unaltered versions
      of the data may not be available, or only selectively so. The public-use version
      of the data is very important because it is likely to be the only one to which
      most researchers, policy analysts, teaching faculty, and students will ever have
      access. Hence, it is the version from which much of the utility of the data is
      extracted and often it effectively becomes the historical record of the data
      collection. This underscores the importance that the disclosure review c ommittee
      s trikes a g ood b alance b etween protection and u tility. In this paper we d
      escrib e our disclosure review committee's (DRC) analysis and resulting data
      protection plans for two national studies and one administrative data system.
      Three distinct disclosure limitation methods were employed, taking key uses of
      the data into consideration, to protect respondents while still providing
      statistically accurate and highly useful public-use data. The techniques include
      data swapping, microaggregation, and suppression of detailed geographic data. We
      describe the characteristics of the data sets that led to the selection of these
      methods, provide measures of the statistical impact, and give details of their
      implementations so that others may also utilize them. We briefly discuss the
      composition of our DRC, highlighting what we believe to be the important
      disciplines and experience represented by the group.

PMID- 19385825
TI  - Solving problems of disclosure risk in an academic setting: using a combination
      of restricted data and restricted access methods.
AB  - THE HEALTH AND RETIREMENT STUDY collects a vast amount of information about a
      sample of the U.S. population over age 50 from biennial interviews, supplemental
      questionnaires, and through linkages with administrative data including Social
      Security earnings and benefits records and Medicare claims records. To h onor i
      ts p ledge to t he r espondents that their data will be kept confidential, but at
      the same time meet its objective of providing useful data to researchers, it has
      develop ed procedures for stripping sensitive information (i.e., information that
      could facilitate re-identification of sample members) from data sets that are
      publicly released, and also for providing mechanisms for qualified researchers to
      gain access to a variety of restricted-access data files. These mechanisms
      include a procedure whereby highly qualified researchersin particular, only those
      who have a current grant from a federal agencycan apply to obtain restricted
      access data sets for a limited amount of time, with the understanding that they
      will make no attempt to r e-identify s amp le m embers and t hat they w ill be
      audited to ensure that they have adhered to the agreedupon safeguards. For those
      who meet some but not all of the requirements for receiving these data, the files
      can be analyzed in a data enclave (a controlled, secure environment in which
      eligible researchers can perform analyses). This paper focuses on approaches to
      restricting data access that may need to be considered by investigators who plan
      to share their data, and by their institutional officials who will need to
      support that effort with appropriate infrastructure and policies. It also
      provides guidance to investigators and institutional review boards (IRBs) who
      seek access to restricted data generated and archived elsewhere.

PMID- 19385826
TI  - Call for abstracts of papers: recovering respect for persons: research involving
      survivors of violence, trauma and stigma.

PMID- 19385827
TI  - Call for Abstracts: Hidden Research Ethics: Ethics Research by any Other Name.

PMID- 19385831
TI  - Empirical Research on IRBs and Methodologies Usually Associated with Minimal
      Risk.

PMID- 19385832
TI  - Educational advantage.

PMID- 19385833
TI  - Research agendas.
AB  - WHILE EACH ARTICLE IN THIS ISSUE OF JERHRE raises important questions that call
      for empirical research, one article-the editorial-subsumes all issues raised by
      the rest of the articles herein. It is a call to make full use of the allowed
      freedom to design an improved system of ethical problem solving and ethical
      oversight in human research. Being an ethical researcher is often cast in terms
      of compliance with ethics committee rules. In some contexts those rules,
      inflexibly applied, may cause unnecessary delay, damage and hindrance to
      important research projects. Stated otherwise, they may impose unethical
      requirements on research. Yet it is the very inaction or compliance of
      researchers and research administrators that causes us to fail to help create
      systems of research oversight that work-that foster valid and ethical research
      and advance human society.

PMID- 19385834
TI  - A Review of Paying Research Participants: It's Time to Move Beyond the ethical
      Debate.
AB  - CURRENT REGULATORY GUIDELINES REQUIRE the ethical review committee to consider
      one question when evaluating payment: Is the payment to the participant undue or
      coercive? Although this is a seemingly simple question, determining appropriate
      payment involves a series of complex issues. There is limited empirical knowledge
      to assist with this determination and little consensus on which elements of a
      study should be considered in making these decisions. For example, should the
      culture of the study population or the potential risks and benefits of the
      research be considered in the selection of appropriate payment? Following a
      review of national and international guidelines, the concerns and benefits of
      paying research participants are presented, and prior ethical debate is outlined.
      The current research literature on the practice of paying participants and the
      impact of payment on participants and study integrity are reviewed. Finally,
      given continued debate with limited data to help determine best practices, a
      research agenda is proposed to assist in the development of an empirical basis to
      aid investigators and ethical review committees in making appropriate decisions
      about payment to research participants.

PMID- 19385835
TI  - The ethics of paying drug users who participate in research: a review and
      practical recommendations.
AB  - THE PAYMENT OF RESEARCH PARTICIPANTS raises ethical and empirical questions that
      have special importance in addictions research involving drugdependent
      participants. Despite a now large literature on human subjects payment, what is
      still needed is practical guidance for investigators and ethics committees. This
      paper reviews the literature on: current payment practices and guidelines;
      defining features of undue and due incentives and fair reimbursement; and the
      significance of risks and harms that may arise from paying drug using
      participants. We conclude that research payments are ethically acceptable in most
      circumstances of addictions research, but should be closely scrutinized in
      situations where these may exacerbate existing harms or create additional risks
      for participants and investigators. General principles, key questions and
      procedural options are highlighted for an applied approach to ethical research
      payments. Future research directions are identified.

PMID- 19385836
TI  - Paying Clinical Research Participants: One Institution's Research Ethics
      Committees' Perspective.
AB  - REGULATORY GUIDELINES LEAVE determination of coercion and undue influence of
      research participants open to interpretation. A web-based survey was conducted of
      the research ethics committees members at Virginia Commonwealth University (VCU)
      to evaluate their perspectives on paying participants in clinical research via
      general questions, as well as 8 short cases involving hypertension placebo
      controlled trials, a pilot exercise study, a survey of substance abusers, a
      healthy-volunteer pharmacokinetic study, a twin study involving DNA samples, and
      an asthma medication study in children. Research ethics committee members were
      asked to state what payment they would consider appropriate for a given type of
      protocol. The results suggest that risk, time required, reimbursement for
      expenses, and inconvenience were important in determining appropriate payment,
      while income and funding source were not. The case studies revealed wide
      variation in recommended payments both within type of study and between studies.

PMID- 19385838
TI  - Methods and practices of investigators for determining participants' decisional
      capacity and comprehension of protocols.
AB  - ETHICISTS RECOMMEND THAT investigators assess subjects' comprehension prior to
      accepting their consent as valid. Because children represent an at-risk
      population, ensuring adequate comprehension in pediatric research is vital. We
      surveyed all corresponding authors of research articles published over a six
      month period in five leading adult and pediatric journals. Our goal was to assess
      how often subject's comprehension or decisional capacity was assessed in the
      consent process, whether there was any difference between adult and pediatric
      research projects, and the rate at which investigators use formal or validated
      tools to assess capacity. Responses from 102 authors were analyzed (response rate
      56%). Approximately two-thirds of respondents stated that they assessed
      comprehension or decisional capacity prior to accepting consent, and we found no
      difference between adult and pediatric researchers. Nine investigators used a
      formal questionnaire, and three used a validated tool. These findings suggest
      that fewer than expected investigators assess comprehension and decisional
      capacity, and that the use of standardized and validated tools is the exception
      rather than the rule.

PMID- 19385839
TI  - Ethical issues in registry research: in-hospital resuscitation as a case study.
AB  - RESEARCH BASED ON REGISTRY STUDIES involves significant ethical issues. Using
      detailed information about one registry concerning in-hospital resuscitation, we
      present issues concerning informed consent, access to identifiable medical
      information, and benefit for participants. In addition, multiple methodological
      difficulties have indirect implications for the ethical conduct of registry
      research, including consensus about variable definitions, validity and
      reliability for clinical decisions, sample sizes, and sources of data. Both
      direct and indirect ethical issues are examined from the viewpoint of accepted
      regulations and codes regarding ethical conduct of research; specific examples of
      more or less ethical solutions to the problems are presented from published
      research.

PMID- 19385837
TI  - Using formative research to develop a context-specific approach to informed
      consent for clinical trials.
AB  - PARTICIPANT UNDERSTANDING is of particular concern when obtaining informed
      consent. Recommendations for improving understanding include disclosing
      information using culturallyappropriate and innovative approaches. To increase
      the effectiveness of the consent process for a clinical trial in Malawi on
      interventions to prevent mother-tochild transmission of HIV during breastfeeding,
      formative research was conducted to explore the community's understanding of
      medical research as well as how to explain research through local terms and
      meanings. Contextual analogies and other approaches were identified to explain
      consent information. Guided by theory, strategies for developing culturally
      appropriate interventions, and recommendations from the literature, we
      demonstrate how the formative data were used to develop culturally appropriate
      counseling cards specifically for the trial in Malawi. With appropriate
      contextual modifications, the steps outlined here could be applied in other
      clinical trials conducted elsewhere, as well as in other types of research.

PMID- 19385840
TI  - Trends in Canadian Sociology Master's Theses in Relation to Research Ethics
      Review, 1995-2004.
AB  - THIS PAPER EXAMINES TRENDS IN CANADIAN Master's theses in sociology, 1995-2004,
      in the course the implementation of Canada's national research-ethics guidelines
      (2001), using data available from ProQuest Dissertations. While there has been no
      decline in the number of theses completed during this period, nearly 1/4 fewer
      theses now involve research participants. The proportion of theses using
      quantitative methods shows decline; theses using qualitative methods, however,
      have increased significantly over time. A closer inspection qualitative theses
      shows an impressive increase in the proportion of theses using interviews, while
      the decrease in theses using field work is even more dramatic, from 40% to 5%.
      The decrease of theses involving field work is particularly alarming for a
      significant segment of sociology that must derive its material mainly from field
      work. Data drawn from a larger study supplement the findings in this article.

PMID- 19385841
TI  - Consultants for 2006.

PMID- 19385845
TI  - Respect for persons and informed consent-a moving target.

PMID- 19385846
TI  - Questioning the Need for Informed Consent: A Case Study of California's
      Experience with a Pilot Newborn Screening Research Project.
AB  - CALIFORNIA PROVIDES MANDATORY newborn screening for disorders that cause
      irreversible, severe disabilities if not identified and treated early in life.
      Parental consent is not required. In 2001, the Genetic Disease Branch was
      mandated to pilot test a new technology that could identify many additional
      disorders using the same blood specimen already collected. Study participation
      required informed consent, which was obtained for 47% of births during the study
      timeframe. The inability of hospitals to carry out the consent procedure for all
      newborns resulted in denial of testing and missed cases. If informed consent were
      waived, all newborns could have been tested. Several empirical questions are
      posed and each is examined from the perspective of society, the parents and the
      newborn. It is concluded that the legitimate needs of society and the interests
      of newborns should not be sacrificed to respond to the autonomy interests of the
      few parents who did not wish their infant to participate in the study, and that
      in the future, parental consent should be waived for projects evaluating new
      screening technologies.

PMID- 19385847
TI  - Cancer patients' attitudes toward future research uses of stored human biological
      materials.
AB  - THE POLICY DEBATE CONCERNING INFORMED consent for future, unspecified research of
      stored human biological materials (HBM) would benefit from an understanding of
      the attitudes of individuals who contribute tissue specimens to HBM repositories.
      Cancer patients who contributed leftover tissue to the Indiana University Cancer
      Center Tissue Bank under such conditions were recruited for a mail survey study
      of their attitudes. Our findings suggest that a clear majority of subjects would
      permit unlimited future research on stored HBMs without re-contact and reconsent,
      and a significant minority appear to desire ongoing control over future research
      uses of their tissue. These differences merit further investigation and suggest
      that a policy of blanket consent for all future, unspecified research would be
      premature.

PMID- 19385848
TI  - Ethics committee experience with emergency exception from informed consent
      protocols.
AB  - SINCE 1996, U.S. FEDERAL REGULATIONS allow research without informed consent to
      study emergency conditions, if there is currently no satisfactory treatment for
      the condition, no time to obtain advance consent from the patient or
      representative, and if there is community involvement through a public disclosure
      and community consultation process. REB experiences since then are unknown. We
      surveyed REB chairpersons at the 126 United States medical schools to quantify
      reviewed protocols and identify attitudes about the rule, to better understand
      the rule's impact on REBs. Sixty-nine surveys were returned (55%). Fifty-two
      respondents reviewing human research had heard of the Rule. Forty-eight percent
      (25/52) had reviewed such a study; 40% of those had rejected at least one.
      Seventy-eight percent believe the rule protects human subjects, and 88% feel
      prepared to implement them. REB views differed from public opinion on how best to
      enact notification and consultation.

PMID- 19385849
TI  - Respondent reactions to sensitive questions.
AB  - WE ADMINISTERED DEBRIEFING PROBES TO gauge respondent discomfort in reaction to
      sensitive questions. These probes assessed respondents' own reactions to being
      asked to report on substance use (subjective discomfort), as well as their
      beliefs about the reaction of others (projective discomfort). We investigated
      whether a sample of men from the general population were more uncomfortable with
      questions about drug use than a sample of men who have sex with men (MSM)
      surveyed from the same city (Chicago). We also investigated whether those who
      disclosed drug use on the survey experienced higher levels of discomfort.
      Contrary to opinions often expressed as research ethics committee (REC)
      recommendations, questions about drug use do not generate much subjective
      discomfort. MSM did not differ from the general population with respect to
      subjective discomfort. General population males did, however, report higher
      levels of "drug specific" projective discomfort. Respondents disclosing recent
      drug use reported higher levels of subjective discomfort. Implications for the
      REC practice, researcher and REC education, and directions for future research
      are discussed.

PMID- 19385850
TI  - Two methods of obtaining informed consent in a genetic epidemiological study:
      effects on understanding.
AB  - THIS STUDY EVALUATED THE EFFECT ON participant understanding and participation
      rates of two different approaches to obtaining informed consent, using 2,192
      actual research subjects in a genetic cohort study. One group received the
      routine approach consisting of written materials and an oral explanation. The
      other group received a more intense approach consisting of educational lectures
      and group meetings in addition to the routine approach. Subjects in the intense
      approach group were relatively more likely to read some or all of the explanatory
      material. Those in the intense group who did not read the material were more
      likely than those in the routine group to express uncertainty about their
      understanding of the research. Those in the intense group who read the material
      perceived that they had a higher level of understanding of the research and this
      was associated with a higher frequency of volunteering to participate. In
      contrast, subjects in the routine group were less likely to read the written
      material, but ironically more likely to assume that they understood what the
      research was about. These rather paradoxical findings raised questions about what
      motivates potential research subjects to become sufficiently engaged to seek
      actual understanding of the research before volunteering.

PMID- 19385851
TI  - Debriefing in deceptive research: a proposed new procedure.
AB  - THIS STUDY EXAMINES THE EFFECTIVENESS of a new debriefing procedure designed
      specifically to address possible negative consequences of participation in
      deceptive research. The new debriefing includes an extended educational procedure
      that enables participants to gain insight into relevant deceptive practices and
      how to recognize and deal effectively with them, and thus end their participation
      with a positive and beneficial learning experience. The usefulness of the new
      tool was analyzed in a suggestibility study in which we compared the effects of
      the standard debriefing and the new procedure in terms of participants' mood,
      self-esteem, and attitudes toward psychological experiments. The most important
      result was that at the end of the study subjects who received the new debriefing
      system expressed more positive mood and more positive attitudes toward research
      than those who received the standard debriefing system. The implications of these
      results for generalizing to other kinds of deception research are discussed.

PMID- 19385852
TI  - Perceptions of stress among students participating in psychology research: a
      canadian survey.
AB  - IT HAS BEEN SHOWN THAT PROPERLY conducted interviews in sensitive clinical
      contexts are negligibly stressful. The present study sought to extend these
      results and determine the perception of stress by research participants in
      nonclinical settings. Students enrolled in first year psychology courses
      typically have the option to receive class credit for research participation in
      studies assumed to pose minimal risk to participants. The perceptions of 101
      student volunteers were examined to determine if they felt that research
      participation was stressful and, if so, what components of the process caused
      their stress. Participants completed a short survey indicating the reasons they
      served as research participants and the degree to which participation was
      stressful. They indicated that research participation was a valuable learning
      experience and the majority felt no stress associated with participation. Stress
      was reported by some due to concerns about confidentiality and evaluation by
      others of their personal performance. In addition, the majority of students
      reported having no knowledge of the ethical review process that preceded their
      participation. It is suggested that students should be informed of the ethical
      review process.

PMID- 19385854
TI  - Educational advantage.

PMID- 19385853
TI  - Effects of human subjects requirements on classroom research: multidisciplinary
      evidence.
AB  - PROFESSORS WHO INCLUDE THEIR STUDENTS as subjects in classroom-based research
      projects typically must submit to a review by their university's research ethics
      committee (REC) even in cases which present only minimal risks, and when the
      investigation is intended for evaluation of teaching approaches only, and not for
      publication. Results of a web-based survey with 378 respondents indicate that the
      perceived costs of the review process may outweigh the perceived benefits to
      subjects. A logistic regression analysis identifies the time it takes to complete
      the review application, the time it takes to receive a response, and the
      necessity of revising a project as significant factors in respondents viewing the
      REC process as a barrier to research. Instituting policies of expedited review
      for minimal-risk classroom research and exempting evaluations that are not to be
      published, both of which are permitted under the current regulations, would
      decrease burdens on both researchers and REC members, and foster improvement of
      teaching.

PMID- 19385855
TI  - Research agendas.

PMID- 19385856
TI  - Call for papers: ethical considerations in community-based participatory
      research: special issue of the journal of empirical research on human research
      ethics.

PMID- 19385860
TI  - The evolution of best ethical practices in human research.
AB  - Ideally, best practices in human research would evolve quickly in the wake of new
      ethical challenges, but in reality such challenges sometimes evoke Procrustean
      new oversight requirements that benefit neither human subjects nor science. The
      rapid advance of new topics, methods and ethical challenges in human research
      inevitably raises questions about the appropriateness of time-honored research
      practices, and about the most intelligent application of ethical principles to
      these new contexts. Such questions typically call for an insightful and nuanced
      understanding of the new context, rather than debate based on older conceptions.
      JERHRE serves as a forum to promote and publish meritorious empirical research on
      ethical issues, designed to enable us to learn from these challenges, and thereby
      hasten the evolution of best ethical practices in human research.

PMID- 19385861
TI  - Letters to the editor.

PMID- 19385862
TI  - Research agendas: an invitation to readers.
AB  - Ethical problem solving in human research is a continuing dialectic. Each
      question that is investigated leads to new questions calling for research.
      Articles published in JERHRE include a research agenda, and questions raised
      elsewhere suggest research agendas publishable here. Pursuit of these research
      agendas will lead to a more comprehensive understanding of effective approaches
      to ethical problem solving. Readers are invited to propose agendas, form
      collaborations, and publish their findings.

PMID- 19385863
TI  - Educational advantage.
AB  - What special advantage does JERHRE offer to research ethics education? Empirical
      research employs concepts and methods for understanding and addressing problems;
      the methods employed can be generalized to related problems in new contexts.
      Research published in JERHRE uses concepts and methods designed to understand and
      solve ethical problems in human research. These tools can be reused by JERHRE's
      readership as part of their learning and problem solving. Instead of telling
      scientists, students, ethics committee members and others what they ought to do,
      educators can use curriculum based on the empirical articles contained in JERHRE
      to enable learners to solve the particular research-related problems they
      confront. Each issue of JERHRE publishes curriculum based on articles published
      therein. The lesson plans are deliberately general so that they can be adapted to
      the particular learners.

PMID- 19385864
TI  - Cognitive interviewing as a tool for improving the informed consent process.
AB  - Consent materials often contain complex information, legalese, and other features
      that render them difficult to comprehend in such a way that consent is truly
      informed. I propose that researchers adapt cognitive interviewing, normally used
      for the pretesting of survey questionnaires, to evaluate the understandability of
      consent materials and the way which subjects use this information to make
      decisions regarding participation. Cognitive interviewing involves the intensive
      probing of small samples of volunteer subjects to elucidate thought processes
      that otherwise remain hidden. Cognitive interviewing can be applied: (a) to
      further the basic science of informed consent; (b) to pretest materials for a
      specific study; and (c) as embedded procedure for assessing subject thought
      processes in the course of obtaining consent.

PMID- 19385865
TI  - Informed consent in international health research.
AB  - Informed consent is universally recognized as a central component of ethical
      conduct in scientific research. Investigators working with diverse populations
      throughout the world face myriad challenges. The application of standards for
      informed consent can be daunting for researchers when they face the pragmatic
      constraints of the field and the reality of cultural beliefs about consent that
      may be in direct conflict with regulatory requirements. This paper explores
      cultural and social factors underlying informed consent for health research with
      diverse populations in international settings. Sociocultural influences on
      comprehension of information, perceptions of risk, and beliefs regarding
      decisional authority are reviewed. The implications of power inequities between
      study sponsors, researchers and participants are also considered. Issues
      associated with the development and preparation of consent forms, including
      translation and documentation are highlighted. Recommendations for good practices
      are outlined and future directions for research are explored.

PMID- 19385867
TI  - JERHRE's First Annual Conference.

PMID- 19385866
TI  - What scientists want from their research ethics committee.
AB  - Whereas investigators have directed considerable criticism against Institutional
      Review Boards (IRBs), the desirable characteristics of IRBs have not previously
      been empirically determined. A sample of 886 experienced biomedical and social
      and behavioral scientists rated 45 descriptors of IRB actions and functions as to
      their importance. Predictions derived from organizational justice research
      findings in other work settings were generally borne out. Investigators place
      high value on the fairness and respectful consideration of their IRBs. Expected
      differences between biomedical and social behavioral researchers and other
      variables were unfounded. Recommendations are offered for educating IRBs to
      accord researchers greater respect and fair treatment.

PMID- 19385870
TI  - Guest editorial: the ethics in human research ethics.
AB  - FALSE, BUT COMMON, ASSUMPTIONS about dilemmas in moral reasoning and the so
      called fact/value dichotomy can impede the prosecution JERHRE's prime aim:
      facilitating ethical problem solving in human research. Research ethics, and the
      development of moral science, demand better assumptions about ordinary everyday
      problem solving morality and the deep-seated connectedness of facts and values.

PMID- 19385872
TI  - Research agendas: an invitation to readers.
AB  - THE AIM OF JERHRE IS TO identify and promote meritorious research and
      collaboration that will enhance human research and promote the evolution of best
      research practices. The purpose of this column is to identify topics in need of
      research and to invite collaboration, as set forth in the March 2006 issue. (See
      http://caliber.ucpress.net/loi/jer). An agenda proposed in this issue is research
      on harms to those who gather data. The scientific and ethical quality of human
      research depends, in large measure, on the persons who work day-to-day gathering
      data. Persons who work under conditions of high stress, or in fear of bodily harm
      are not in the best position to gather high quality data or attend fully to
      ethical aspects of research conduct.

PMID- 19385873
TI  - Educational advantage.
AB  - WHAT SPECIAL ADVANTAGE DOES JERHRE offer to research ethics education? Empirical
      research employs concepts and methods for understanding and addressing problems;
      the methods employed can be generalized to related problems in new contexts.
      Research published in JERHRE uses concepts and methods designed to understand and
      solve ethical problems in human research. These tools can be reused by JERHRE's
      readership as part of their learning and problem solving. Instead of telling
      scientists, students, ethics committee members and others what they ought to do,
      educators can use curriculum based on the empirical articles contained in JERHRE
      to enable learners to solve the particular research-related problems they
      confront. Each issue of JERHRE publishes curriculum based on articles published
      therein. The lesson plans are deliberately general so that they can be adapted to
      the particular learners.

PMID- 19385874
TI  - Research sponsorship, financial relationships, and the process of research in
      pharmaceutical clinical trials.
AB  - THE EFFECTS OF SPONSORSHIP AND FINANCIAL relationships on the conduct of clinical
      trials were examined by surveying 321 authors who had published reports of
      pharmaceutical clinical trials. The survey asked about research sponsorship,
      financial relationships, who controlled the research, and who carried it out. W
      hen a commercial s ponsor w as t he e xclusive research sponsor, authors reported
      less control over and less contribution to the research, and more sponsor control
      and contribution, as compared with noncommercial or mixed sponsorship. Similarly,
      financial relationships with firms were associated with less author contribution
      to and more sponsor control over and contribution to the research. The results
      raise concerns about bias in the design, conduct, or reporting of research.

PMID- 19385875
TI  - Resisting power and influence: a case study in virtue ethics.
AB  - THIS IS A CASE STUDY based on the author's experience while serving as an ethics
      committee (IRB) chair in New York City. It addresses the issues of power and
      coercion as they apply to the human research participants protection process. It
      primarily focuses on the power imbalance that can exist between research
      participants and their IRB advocates on the one hand and the research
      institutions, funding agencies, and investigators with their unlimited resources
      on the other. IRB Chairs and IRB leaders must be fire-walled from conflicts of
      interest arising not just from financial factors but from factors related to
      power, hierarchy, structure, and control. Senior staff, IRB members,
      administrators and ethicists best advocate for human volunteers in research
      through personal identification and solidarity.

PMID- 19385876
TI  - A needs assessment to build international research ethics capacity.
AB  - INTERNATIONAL COLLABORATORS IN BIOMEDICAL sciences face ethical challenges in the
      design, review, and conduct of research. Challenges include differences in
      research ethics capacity, cultural differences in interpretation and application
      of ethical principles, and cooperation between ethics review boards at
      collaborating institutions. Indiana University School of Medicine (Indianapolis,
      USA) and Moi University Faculty of Health Sciences (Eldoret, Kenya) developed a
      Memorandum of Understanding (MOU) to establish greater cooperation between their
      ethics review boards, followed by a joint needs assessment to assess barriers to
      implementing the MOU. Focus groups and interviews at each institution revealed
      that while each side verbalized understanding and respect for the other's
      culture, there were misunderstandings deeply rooted in each culture that could
      potentially derail the collaboration. Although the participants at each
      university agreed on the major principles and issues in research ethics and on
      the importance attributed to them, a more in-depth evaluation of the responses
      revealed important differences. Methods to address these misunderstandings are
      outlined in the recommended Best Practices.

PMID- 19385877
TI  - U. S. Health Researchers Review their Ethics Review Boards: A Qualitative Study.
AB  - VIRTUALLY ALL RESEARCH INVOLVING HUMAN subjects in the United States must be
      reviewed by an institutional review board, a form of research ethics review
      board. This article reports the results of qualitative research on how
      investigators regard this regulatory regime. Interviews were conducted with forty
      investigators conducting health-related research. Most respondents shared the
      regulations' goals, but doubted that the regulations, as implemented, promoted
      these goals efficiently, effectively and fairly. The interviews suggest that
      efforts to raise researchers' ethical consciousness have been, over time, quite
      successful, but that implementation of the regulations remains problematic.
      Research aimed at better defining the problem to be solved b y the r egulatory sy
      stem, and at a ssessing the effectiveness of the regulatory tools for solving
      properly defined problems, could guide a more productive debate about human
      subject protection.

PMID- 19385878
TI  - Anthropological Research in Light of Research-Ethics Review: Canadian Master's
      Theses, 1995-2004.
AB  - DESPITE CLAIMS THAT RESEARCH-ETHICS review is changing or discouraging social
      research, there are no studies that have tested this assumption. Examining
      Canadian Master's theses in anthropology between 1995 and 2004, this paper
      explores the extent to which the theses represent a change in number, topic, or
      methodology in relation to formal ethicsreview guidelines that came into force in
      Canada in 2001. ProQuest Digital Dissertations reveals that the number of theses
      has increased, and that there has not been a noticeable shift from research
      involving humans to research based on archival data, or theoretical or review
      theses. However, there has been a very significant increase in research that is
      called ethnography, but that relies exclusively on interviews. Possible reasons
      for the halving of percent of ethnographic or participantobservation research are
      explored.

PMID- 19385879
TI  - If Ethics Committees were Designed for Ethnography.
AB  - WHERE DID THE ETHICS REVIEW PROCESS go wrong for qualitative research, and how
      can we make it right, or at least better? This paper begins with an excerpt from
      an ethnography of attempting to attend an ethics review-related workshop, which
      exemplifies that the ethics-review process is based on epistemological
      assumptions aligned with positivistic research, and does not fit the qualitative
      research process. We suggest that a new format for ethics review, based on
      assumptions associated with qualitative research and ethnography, might be a
      better fit. In this model the researcher becomes the expert and the committee the
      learner or ethnographer. In this process the ethics review process is guided by
      four core open-ended questions that facilitate a fuller and richer exchange of
      information. The second part of this paper presents strategies that may lessen
      the risks associated with the unknown or emergent aspects of qualitative
      research. These strategies include a dual consent process and the co-opting of
      journal editors or thesis review boards to review ethical considerations prior to
      publication or sign off, and a renewed focus of ethics training.

PMID- 19385880
TI  - The Anthropologist and the Crayons: Changing our Focus from Avoiding Harm to
      Doing Good.
AB  - THE ETHICAL REVIEW PROCESS is aimed at protecting research participants,
      evaluating risk in relation to benefit, and, where possible, reducing risk to
      research participants (and by extension, to the sponsoring organizations). In
      practice, however, there is usually much focus on risk and little on benefit.
      However, social research presents an opportunity to give active benefits to many
      constituents: the research participants, the host community, the researcher and
      research team members, the sponsoring institution and funding agency, the
      academic community, and society at large. Even when benefits are considered, the
      proximal benefits-those that actually accrue during (and because of) the
      investigator's presence-are too often overlooked by both investigators and ethics
      committees in favor of the more distal benefits related to the contribution to
      knowledge. The research design and review processes can both be redirected to
      focus more centrally on imagining, creating and extending the benefits of our
      work.

PMID- 19385881
TI  - JERHRE's New Web Pages.
AB  - JERHRE'S WEBSITE, www.csueastbay.edu/JERHRE/ has two new pages. One of those
      pages is devoted to curriculum that may be used to educate students,
      investigators and ethics committee members about issues in the ethics of human
      subjects research, and to evaluate their learning. It appears at
      www.csueastbay.edu/JERHRE/cur.html. The other is devoted to emailed letters from
      readers. Appropriate letters will be posted as soon as they are received by the
      editor. Letters from readers appear at www.csueastbay.edu/JERHRE/let.html.

PMID- 19385882
TI  - JERHRE's First Annual Conference.

PMID- 19385883
TI  - Call for abstracts of papers.

PMID- 19385887
TI  - What is the Value of a Timely Empirical Question?
AB  - ETHICAL ANALYSIS IN THE HUMAN research enterprise often proceeds on the
      assumption that conceptual ethical analysis alone will suffice. Investigators,
      ethics committees and others usually agree on the relevant ethical principles,
      but may argue about what action should follow from those principles. Typically,
      the debate does not lead to the formulation of empirical questions that could
      result in elucidation of the problem and, perhaps, yield a solution agreeable to
      all. Without common ground for resolving these differences with an evidence-based
      solution, a discouraged investigator and a compromised research method may be the
      outcome. JERHRE has sought to remedy this situation through publication of
      empirical solutions, research agendas, editorials calling for various courses of
      empirical research, and through the first of many conferences seeking to promote
      evidence-based ethical problem solving. This special issue of JERHRE is devoted,
      in part, to the results of that first conference.

PMID- 19385888
TI  - Sharing Data and Results in Ethnographic Research: Why This Should not be an
      Ethical Imperative.
AB  - RESEARCHERS RECENTLY HAVE argued that offering to share research results with
      study participants should be an "ethical imperative." This article considers that
      suggestion in light of the practice of ethnographic, particularly
      anthropological, research. Sharing results is discussed in relation to several
      issues, e.g., whether it occurs during or after completion of a project, whether
      the research is long-term, the complexities involved in depositing field
      materials in archives, the changing politics of ethnographic research, research
      not concerned with communities, situations in which participants and the
      anthropologist may be in danger, and changing styles of ethnographic research. I
      argue that, ideally, sharing should be a regular component of ethnographic
      research but should not be an ethical requirement. Given the complexity, variety
      and changing political contexts of ethnographic research, implementing such a
      requirement would often be practically impossible and sometimes would be
      inadvisable. I recommend instead that research ethics boards educate themselves
      about the nature of ethnographic research. Further, they should approach decision
      making on the issue of data or results sharing on a case-by-case basis. For
      researchers, I recommend that discussion of data and result sharing should become
      part of the education of all ethnographers and that discussion of the issue
      should be fostered.

PMID- 19385889
TI  - Establishment of a standing ethics/institutional review board in a nigerian
      university: a blueprint for developing countries.
AB  - AN ETHICS/INSTITUTIONAL REVIEW BOARD (IRB) was established according to
      International standards at the University of Ibadan in Nigeria. To achieve this,
      a private-public partnership was developed to support a review of prevailing
      practice and the development of necessary infrastructure for an effective IRB. An
      internationally registered and well-constituted IRB with a federal-wide assurance
      (FWA) from the National Institute of Health in the United States was established
      within a year. Over a 3-year period, the number of proposals reviewed increased
      by 150% while time to approval decreased by 62%. International collaboration and
      external research funding has increased substantially. These findings support our
      initial supposition that the development of a properly functioning IRB can be a
      catalyst for increased research productivity at academic centers in developing
      countries while ensuring the protection of vulnerable human research subjects.
      The University of Ibadan is now assisting other academic Institutions in Nigeria
      and sub-Saharan Africa with the establishment of their own IRBs.

PMID- 19385890
TI  - Community-based participatory research and the ethics review process.
AB  - THIS EXPLORATORY STUDY EXAMINES the experiences of community-based participatory
      researchers' (CBPR) with the IRB. CBPR is oftentimes applied to non-clinical
      questions where academic researchers collaborate with community partners to
      address local concerns. Constant Comparative Method guided the analysis of ten
      CBPR interviews. The interview questions included: How does your
      conceptualization of research coincide with the regulations' definition? How are
      community partners involved in the IRB process? What are the benefits/challenges
      of the IRB process? And, what recommendations do you have to strengthen the IRB
      process? The article concludes with suggestions for IRB reviewers and CBPR
      partners on how to facilitate the review of CBPR projects.

PMID- 19385891
TI  - Content Among Locally Approved HIPAA Authorization forms for Research.
AB  - THIS STUDY WAS DESIGNED TO ASSESS differences in the content of HIPAA
      authorization forms now required for clinical research. Authorization forms were
      collected from 111 institutions, including academic medical centers and
      commercial Institutional Review Boards. The requirement for an element covering
      the use of information acquired was fulfilled in 95% of the forms, and 100% had a
      statement fulfilling the core requirement of a description of the data to be
      collected. However, only 19% distinguished between entities that could see
      personal identifiers versus aggregate data. Significant differences existed in
      how long the disclosure agreement would remain in effect, and complex legalistic
      language was common. Thus, while research authorization forms technically met the
      requirements, the complex language and confusion over personal identifiers may
      raise concerns in prospective research participants.

PMID- 19385892
TI  - Educational advantage.
AB  - THE RESEARCH ARTICLES IN THE March 2007 issue of JERHRE explore two major topics:
      * Research methods wherein the investigator does not have unilateral control over
      the setting, as in ethnography and community-based participatory research, raise
      special problems of ethical oversight and problem solving. * Introducing new
      ethical oversight, whether developing an effective ethics committee in a
      developing country or implementing HIPAA requirements in human research, call for
      mindfulness of ethical objectives rather than simple rule following. JERHRE has
      an advantage in the ethics education arena. Lecturing about what should be done
      is an ineffective way to change people's hearts and minds, much less their
      behavior. In contrast, JERHRE provides concepts and methods that learners can use
      to discover for themselves what should be done. In the process, learners discover
      that what they should do is synonymous with what is in their best interests. Such
      is the persuasive power of evidence-based ethical problem solving.

PMID- 19385893
TI  - Special section of research agendas: ethical issues and empirical questions.

PMID- 19385894
TI  - Trauma research.

PMID- 19385895
TI  - Exposure to emotionally evocative media.

PMID- 19385896
TI  - Involuntary commitment by relatives.

PMID- 19385897
TI  - Assessing Incidence of Sexual Assault (SA) and Needs of SA Survivors Via Random
      Digit Dialing.

PMID- 19385899
TI  - Summary of empirical questions pertaining to trauma research.

PMID- 19385898
TI  - Challenges of research on women veterans with traumatic stress disorders.

PMID- 19385900
TI  - Interviewing children of a parent with a serious mental illness.

PMID- 19385901
TI  - Mandated reporting.

PMID- 19385902
TI  - Mandatory Reporting: How much detail about risk should subjects receive?

PMID- 19385903
TI  - The privacy of stigmatized persons.

PMID- 19385904
TI  - Recruitment of Men Having Sex with Men (MSM) Who Use Illegal Drugs.

PMID- 19385905
TI  - Registered sex offender study.

PMID- 19385906
TI  - Researching hidden networks.

PMID- 19385907
TI  - Creating social change and protecting research.

PMID- 19385908
TI  - Privacy in organizational research.

PMID- 19385909
TI  - Studying IRB Processes.

PMID- 19385910
TI  - Behavior, leadership and economic success.

PMID- 19385911
TI  - Informed consent.

PMID- 19385912
TI  - The Interviewee Who is Reluctant to Sign a Consent Form Until After the
      Interview.

PMID- 19385913
TI  - Teen smoking cessation programs-when parental permission increases risk.

PMID- 19385914
TI  - Research in emergency situations: community consultation and public disclosure.

PMID- 19385915
TI  - Informed Consent and Assent Decisions by Persons with Dementia and their Legally
      Designated Representatives.

PMID- 19385916
TI  - Pain Relief After Acute Injury and/or Emergent Surgery.

PMID- 19385918
TI  - Cultural competence of researchers.

PMID- 19385917
TI  - Informed consent for research with children on mechanical ventilation.

PMID- 19385919
TI  - Obtaining informed consent for research on immigrant populations.

PMID- 19385920
TI  - Making research trustworthy for native americans.

PMID- 19385921
TI  - Deception in psoriasis study involving greater than minimal risk.

PMID- 19385922
TI  - Deception.

PMID- 19385923
TI  - Effects of social variables on cheating.

PMID- 19385924
TI  - The water purification study.

PMID- 19385925
TI  - Protecting researchers.

PMID- 19385926
TI  - Tobacco sale to minors.

PMID- 19385927
TI  - Tobacco sale to minors.

PMID- 19385928
TI  - Travel Advisory Requirement: Is this Abusive Bureaucracy at Work?

PMID- 19385929
TI  - Interviewer safety.

PMID- 19385930
TI  - Sharing data, DNA and tissue samples.

PMID- 19385931
TI  - Making public DNA sequencing data from children.

PMID- 19385932
TI  - Acceptable Use of a Large Volume of Tissue Samples for Research Purposes without
      Consent.

PMID- 19385933
TI  - Family Educational Rights and Privacy Act (FERPA).

PMID- 19385934
TI  - No Child Left Behind: Math Coaches Project (MCP).

PMID- 19385935
TI  - Release of student contact information for research recruitment.

PMID- 19385936
TI  - Preeclamptic toxemia: a disease ripe for proteomic discovery.

PMID- 19385937
TI  - Proteomics in prenatal diagnosis.

PMID- 19385938
TI  - Quantitative proteomics and biomarker discovery in human cancer.

PMID- 19385940
TI  - Advanced proteomic technologies for cancer biomarker discovery.
AB  - Proteomic technologies have experienced major improvements in recent years. Such
      advances have facilitated the discovery of potential tumor markers with improved
      sensitivities and specificities for the diagnosis, prognosis and treatment
      monitoring of cancer patients. This review will focus on four state-of-the-art
      proteomic technologies, namely 2D difference gel electrophoresis, MALDI imaging
      mass spectrometry, electron transfer dissociation mass spectrometry and reverse
      phase protein array. The major advancements these techniques have brought about
      and examples of their applications in cancer biomarker discovery will be
      presented in this review, so that readers can appreciate the immense progress in
      proteomic technologies from 1997 to 2008. Finally, a summary will be presented
      that discusses current hurdles faced by proteomic researchers, such as the wide
      dynamic range of protein abundance, standardization of protocols and validation
      of cancer biomarkers, and a 5-year view of potential solutions to such problems
      will be provided.

PMID- 19385941
TI  - Postgenomics of Neisseria meningitidis: an update.
AB  - Neisseria meningitidis infection represents a major life-threatening bacterial
      disease worldwide. Genomics has revolutionized every aspect of the field of
      microbiology. As a consequence of genome sequencing, the postgenomic era
      commenced 15 years ago. Comparative genomics, functional genomics and proteomics,
      as well as a combination of these techniques, will play important roles in
      providing vital information regarding bacterial biological complexity and
      pathogenic traits, and accelerate the development of therapeutic drugs and
      vaccines for combating infections. This review summarizes the current knowledge
      regarding different approaches aimed to shed light on meningococcal biology and
      pathogenesis, and to accelerate the development and characterization of vaccines
      against pathogenic meningococci.

PMID- 19385942
TI  - Protein microarrays: high-throughput tools for proteomics.
AB  - Protein microarrays are versatile tools for parallel, miniaturized screening of
      binding events involving large numbers of immobilized proteins in a time- and
      cost-effective manner. They are increasingly applied for high-throughput protein
      analyses in many research areas, such as protein interactions, expression
      profiling and target discovery. While conventionally made by the spotting of
      purified proteins, recent advances in technology have made it possible to produce
      protein microarrays through in situ cell-free synthesis directly from
      corresponding DNA arrays. This article reviews recent developments in the
      generation of protein microarrays and their applications in proteomics and
      diagnostics.

PMID- 19385943
TI  - Puzzle of protein complexes in vivo: a present and future challenge for
      functional proteomics.
AB  - Complete description of the complex network of cellular mechanisms and use of the
      network to predict the full range of cellular behaviors are major goals of
      systems biology. A key role in contemporary biology can be played by functional
      proteomics, which focuses on the elucidation of protein functions and the
      definition of cellular mechanisms at the molecular level. The attainment of these
      targets is strictly dependent on the identification of individual proteins within
      functional complexes in vivo. Isolation of interacting proteins relies on either
      affinity-based or immunoprecipitation procedures in which the protein bait and
      its specific partners can be fished out by their specific binding to ligand
      molecules immobilized on insoluble supports. These approaches led to the final
      identification of several proteins belonging to distinct complexes endowed with
      different biological functions. Assignment of each protein to a specific complex
      constitutes a tremendous problem that can only be partially solved using protein
      protein interaction databases and literature information. The development of
      prefractionation methodologies to separate individual protein complexes while
      preserving their native interactions might then represent an essential tool for
      the future of functional proteomics. Prepurification of single complexes can only
      be pursued under native conditions on the basis of their physicochemical
      features, such as size, dimension (gel filtration chromatography) and density
      (gradient ultracentrifugation). Following prefractionation, the complex
      associated to a specific biological function can be isolated using affinity
      purification techniques. Functional proteomics approaches able to describe
      individual proteins belonging to complexes involved in specific cellular
      functions will have a terrific impact on future systems biology studies.

PMID- 19385944
TI  - Utility of mass spectrometry for proteome analysis: part II. Ion-activation
      methods, statistics, bioinformatics and annotation.
AB  - This is the second article in a series, intended as a tutorial to provide the
      interested reader with an overview of the concepts not covered in part I, such
      as: the principles of ion-activation methods, the ability of mass-spectrometric
      methods to interface with various proteomic strategies, analysis techniques,
      bioinformatics and data interpretation and annotation. Although these are
      different topics, it is important that a reader has a basic and collective
      understanding of all of them for an overall appreciation of how to carry out and
      analyze a proteomic experiment. Different ion-activation methods for MS/MS, such
      as collision-induced dissociation (including postsource decay) and surface
      induced dissociation, electron capture and electron-transfer dissociation,
      infrared multiphoton and blackbody infrared radiative dissociation have been
      discussed since they are used in proteomic research. The high dimensionality of
      data generated from proteomic studies requires an understanding of the underlying
      analytical procedures used to obtain these data, as well as the development of
      improved bioinformatics tools and data-mining approaches for efficient and
      accurate statistical analyses of biological samples from healthy and diseased
      individuals, in addition to determining the utility of the interpreted data.
      Currently available strategies for the analysis of the proteome by mass
      spectrometry, such as those employed for the analysis of substantially purified
      proteins and complex peptide mixtures, as well as hypothesis-driven strategies,
      have been elaborated upon. Processing steps prior to the analysis of mass
      spectrometry data, statistics and the several informatics steps currently used
      for the analysis of shotgun proteomic experiments, as well as proteomics
      ontology, are also discussed.

PMID- 19385945
TI  - Protozoan parasite aquaporins.
AB  - Protozoan parasites are a major threat to human health with millions of
      fatalities worldwide, especially in nonindustrialized countries. Currently, there
      is no cure for many of these parasitic diseases. Consequently, there is an
      imperative to find treatment targets and develop novel drugs based on the
      proteins encoded in the genomes of these parasites. Aquaporins, members of
      membrane proteins discovered and characterized within the past 20 years, are the
      mechanism through which water is transported through living membranes. The
      presence of aquaporins explains disease etiology related to water physiology and
      presents new pharmacogenomic targets. In this article, we review the literature
      on aquaporins found in Apicomplexan, Kinetoplastida and Microsporidia parasites
      as potential drug targets. Furthermore, by analyzing protein motion dynamics, we
      identify impediments that need to be surmounted for developing effective drugs
      targeting the aquaglyceroporin of Plasmodium falciparum, the causative agent of
      the most fatal form of human malaria.

PMID- 19385947
TI  - Dynamic aspects of ascorbic acid metabolism in the circulation: analysis by
      ascorbate oxidase with a prolonged in vivo half-life.
AB  - Because AA (L-ascorbic acid) scavenges various types of free radicals to form
      MDAA (monodehydroascorbic acid) and DAA (dehydroascorbic acid), its regeneration
      from the oxidized metabolites is critically important for humans and other
      animals that lack the ability to synthesize this antioxidant. To study the
      dynamic aspects of AA metabolism in the circulation, a long acting AOase
      (ascorbate oxidase) derivative was synthesized by covalently linking PEG
      [poly(ethylene glycol)] to the enzyme. Fairly low concentrations of the modified
      enzyme (PEG-AOase) rapidly decreased AA levels in isolated fresh plasma and blood
      samples with a concomitant increase in their levels of MDAA and DAA. In contrast,
      relatively high doses of PEG-AOase were required to decrease the circulating
      plasma AA levels of both normal rats and ODS (osteogenic disorder Shionogi) rats
      that lack the ability to synthesize AA. Administration of 50 units of PEG
      AOase/kg of body weight rapidly decreased AA levels in plasma and the kidney
      without affecting the levels in other tissues, such as the liver, brain, lung,
      adrenal grand and skeletal muscles. PEG-AOase slightly, but significantly,
      decreased glutathione (GSH) levels in the liver without affecting those in other
      tissues. Suppression of hepatic synthesis of GSH by administration of BSO [L
      buthionin-(S,R)-sulfoximine] enhanced the PEG-AOase-induced decrease in plasma AA
      levels. These and other results suggest that the circulating AA is reductively
      regenerated from MDAA extremely rapidly and that hepatic GSH plays important
      roles in the regeneration of this antioxidant.

PMID- 19385948
TI  - Lipoxin A4 generation is decreased in aspirin-sensitive patients in lysine
      aspirin nasal challenge in vivo model.
AB  - BACKGROUND: Lipoxins represent a group of lipoxygenase derived eicosanoids which,
      in contrast to leukotrienes, are potent anti-inflammatory mediators. The aim of
      our study was to determine lipoxin A(4) (LXA(4)) and leukotriene C(4) (LTC(4))
      levels in nasal lavages after intranasal challenge with aspirin in aspirin
      intolerant (AIA) in comparison to aspirin tolerant (ATA) asthmatics and after
      allergen challenge in patients suffering from allergic rhinitis. METHODS: Twelve
      AIA, 8 ATA and 20 allergic patients were challenged with placebo, 16 mg of lysine
      aspirin (Lys-ASA) or allergen (grasses). Nasal lavages were collected and
      eicosanoids' levels were determined using ELISA. RESULTS: Clinically positive Lys
      ASA challenge in AIA resulted in influx of leukocytes (eosinophils and basophils)
      to nasal secretions and increase of LTC(4) to 106.82 pg/ml (P < 0.05 vs baseline
      (26.58 pg/ml)) on first hour after the challenge. We did not observe any
      differences in LTC(4) level before and after ASA challenge in ATA. In AIA group
      the mean level of LXA(4) was 43 +/- 21.5 pg/ml after placebo and decreased in 2 h
      after Lys-ASA challenge (29 +/- 17 pg/ml, P = 0.015). We found an increase in
      LXA(4) in ATA after ASA provocation as compared to placebo (33 +/- 16 pg/ml vs 52
      +/- 31 pg/ml, P = 0.046). In atopic patients baseline level of LXA(4) was 33.49
      +/- 16.95 pg/ml with no difference after the clinically positive allergen
      challenge (36.22 +/- 13.26 pg/ml, P = 0.23). CONCLUSIONS: Results of our study
      confirm that AIA have diminished LXs' biosynthesis capacities in vivo after ASA
      challenge. Taking into consideration anti-inflammatory properties of lipoxins
      this phenomenon may be partially responsible for the development of chronic
      inflammation in AIA patients.

PMID- 19385949
TI  - Vacuum-assisted delivery is associated with late-onset asthma.
AB  - BACKGROUND: Perinatal factors during delivery might modulate fetal immunological
      development and thereby be associated with the development of allergic diseases
      and asthma later. METHODS: Perinatal data was recorded during pregnancy and at
      the time of delivery in regard to 5823 children who were born in Northern Finland
      in 1985-1986. Data from self-administered questionnaires were available at the
      ages of 7 and 15-16 years and skin prick tests for four main allergens were
      carried out at the age of 15-16 years. Only singletons delivered by the vaginal
      route were analyzed. RESULTS: There was a higher prevalence of doctor-diagnosed
      asthma at any time of life among children who were delivered by vacuum extraction
      (RR 1.80, 95% CI 1.27-2.56; P < 0.001) in comparison with spontaneously delivered
      children. In particular, this risk was increased as regards late-onset asthma (RR
      2.41, 95% CI 1.52-3.81; P < 0.001). Perinatal effects had less impact on the
      development of other asthma, atopy or hay fever. CONCLUSIONS: The delivery by
      vacuum extraction had significant impact on the development of late-onset asthma
      compared with spontaneously delivered children.

PMID- 19385950
TI  - Cefaclor anaphylaxis in children.

PMID- 19385951
TI  - 'Well days' after sublingual immunotherapy with a high-dose 6-grass pollen
      preparation.

PMID- 19385952
TI  - Allergen content of grass pollen preparations for skin prick testing and
      sublingual immunotherapy.
AB  - BACKGROUND: The allergen content of diagnostics and immunotherapeutics is crucial
      for effective diagnosis and treatment. The aim of this study was to quantify and
      compare the allergen content of different grass pollen preparations for skin
      prick testing and sublingual immunotherapy (SLIT). METHODS: Five skin prick test
      (SPT) solutions and 10 sublingual immunotherapeutics were analysed for protein
      and allergen concentration by Bradford assay, inhibition of IgE-binding to Phleum
      pratense ImmunoCAPs and content of the main allergen Phl p 5 by two-site enzyme
      immunoassay. In addition, the grass pollen preparations were compared by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting
      analyses. RESULTS: Protein concentrations of SPT solutions ranged from 15 to 427
      microg/ml, and Phl p 5 concentrations ranged from 0.15 to 18.3 microg/ml. The
      ranking of SPT solutions concerning Phl p 5 content and IgE inhibition capacity
      was the same, and the ranking of protein and allergen content was closely
      correlated (r = 0.9). Protein content of the maintenance doses of the
      immunotheurapeutics ranged from 5 to 153 microg, Phl p 5 content ranged from 0.2
      to 21.6 microg. IgE inhibition capacity of the maintenance doses was closely
      correlated to their Phl p 5 and protein content. SDS-PAGE and immunoblots
      confirmed the differences in protein and allergen content. CONCLUSIONS: Grass
      pollen preparations for SPT and SLIT varied greatly concerning protein and
      allergen content. Whereas this result corresponds to previous analyses results of
      SPT solutions, it was the first comparison of grass pollen immunotherapeutics.
      For diagnosis and therapy, these differences should be taken into account.

PMID- 19385954
TI  - Abstracts of the American Transplant Congress 2009. May 29-June 3, 2009. Boston,
      Massachusetts, USA.

PMID- 19385958
TI  - The EuroPrevall surveys on the prevalence of food allergies in children and
      adults: background and study methodology.
AB  - BACKGROUND: The epidemiological surveys in children and adults of the EU-funded
      multidisciplinary Integrated Project EuroPrevall, launched in June 2005, were
      designed to estimate the currently unknown prevalence of food allergy and
      exposure to known or suspected risk factors for food allergy across Europe. We
      describe the protocol for the epidemiological surveys in children and adults.
      This protocol provides specific instructions on the sampling strategy, the use of
      questionnaires, and collection of blood samples for immunological analyses.
      METHODS: The surveys were performed as multi-centre, cross-sectional studies in
      general populations. Case-control studies were nested within these surveys. The
      studies in children aged 7-10 years and adults aged 20-54 years were undertaken
      in eight centres representing different social and climatic regions in Europe.
      RESULTS: After a community-based survey collecting basic information on adverse
      reactions to foods, all those stating they had experienced such reactions, as
      well as of a random sample of those stating 'no reactions' to foods, completed a
      detailed questionnaire on potential risks and exposures. Also a blood sample was
      taken to allow serological analysis to establish patterns of food and
      aeroallergen sensitization. We also included a questionnaire to schools on their
      preparedness for dealing with food allergy amongst pupils. Subjects reporting
      adverse reactions to foods and sensitized to the same food(s) were called in for
      a full clinical evaluation that included a double blind placebo controlled food
      challenge (DBPCFC), following a protocol which is described in detail elsewhere.
      CONCLUSIONS: The outcome of these studies will help to improve our understanding
      of several important aspects of food allergies in the European Community,
      providing for more well-informed policies and effective measures of disease
      prevention, diagnosis and management.

PMID- 19385959
TI  - Counter regulation of the high affinity IgE receptor, FcepsilonRI, on human
      airway dendritic cells by IL-4 and IL-10.
AB  - BACKGROUND: Immunoglobulin E is a signalling molecule within the environment of
      the respiratory tract, the high affinity receptor for which, FcepsilonRI, is
      expressed by dendritic cells (DC). Little is known, however, of the expression
      and function of FcepsilonRI on DC in the human respiratory tract. METHODS:
      CD1c(+) DC were purified from surgically resected nasal turbinates of 11 atopic
      and 12 nonatopic patients with chronic rhinosinusitis. Expression of FcepsilonRI
      was determined by flow cytometry. Cytokine production by DC was determined by
      cytometric bead array. RESULTS: Expression of FcepsilonRI was significantly
      elevated on respiratory tract dendritic cells (RTDC) from atopic as compared to
      nonatopic patients. Activation of RTDC through FcepsilonRI induced production of
      the pro-inflammatory cytokines IL-6 and TNF-alpha, and the anti-inflammatory
      cytokine IL-10. The production of IL-6 and TNF-alpha was elevated in atopic
      compared to nonatopic patients studied. Conversely IL-10 production was elevated
      in nonatopic patients. Concomitant activation of FcepsilonRI and stimulation of
      RTDC with IL-4 inhibited production of IL-10 by RTDC. Neutralization experiments
      with anti-IL-10 Ab enhanced whereas addition of exogenous IL-10 to RTDC inhibited
      FcepsilonRI-mediated inflammatory cytokine production. CONCLUSION: The function
      of FcepsilonRI on RTDC from patients with rhinosinusitis is susceptible to
      counter regulation by IL-4 and IL-10.

PMID- 19385960
TI  - Transient high glycaemic intake in the last trimester of pregnancy increases
      offspring birthweight and postnatal growth rate in sheep: a randomised control
      trial.
AB  - OBJECTIVE: Investigate the effect of transient hyperglycemic intake (analogous to
      snacking on high glycaemic foods) in the third trimester of pregnancy on
      offspring birthweight and subsequent growth in sheep. DESIGN: Randomised trial.
      SETTING: University research farm. SAMPLE: Third trimester pregnant ewes.
      METHODS: Ewes were blocked on weight, age and litter size and were randomly
      assigned to receive oral administration of 100 ml of propylene glycol (PG; n =
      51) or 100 ml of water (control, C; n = 53) twice/day. Twice during treatment, 12
      ewes from each group were selected and blood samples collected to determine the
      glucose and insulin response to treatment. MAIN OUTCOME MEASURES: At birth, blood
      was collected from the lambs, their body dimensions measured and body weights
      recorded at 0, 6 and 12 weeks of age after which lambs were slaughtered when they
      reached 40 kg live weight. RESULTS: Administration of PG elevated (P < 0.05)
      plasma glucose and insulin concentrations for 2 hours post administration
      compared with control ewes. Lambs (C: n = 80; PG: n = 70) born to ewes fed high
      glycaemic meals had higher birthweights (C: 5.01 +/- 0.18 kg; PG: 5.27 +/- 0.22
      kg, P = 0.032), plasma glucose concentrations (P = 0.001) and ponderal index
      (weight/height(3), P = 0.043) and reached a similar (P > 0.05) slaughter carcass
      weight (C: 20.0 +/- 0.51 kg; PG: 20.6 +/- 0.55 kg) at an earlier age (PG: 166.0
      +/- 13.2; C: 183.4 +/- 13.8 days, P = 0.039) compared with control lambs.
      CONCLUSIONS: Transient high glycaemic intakes in the third trimester of pregnancy
      resulted in heavier offspring at birth that had faster growth rates in early
      postnatal life. This animal model is relevant for studying the relationship
      between maternal diet, fetal size and the risk of childhood obesity.

PMID- 19385961
TI  - Choice and birth method: mixed-method study of caesarean delivery for maternal
      request.
AB  - OBJECTIVE: To explore whether women view decision-making surrounding vaginal or
      caesarean birth as their choice. DESIGN: Longitudinal cohort study utilising
      quantitative (questionnaire, routinely collected data) and qualitative (in-depth
      interviews) methods simultaneously. SETTING: A large hospital providing National
      Health Service maternity care in the UK. SAMPLE: Four-hundred and fifty-four
      primigravid women. METHODS: Women completed up to three questionnaires between
      their antenatal booking appointment and delivery. Amongst these women, 153 were
      interviewed at least once during pregnancy (between 24 and 36 weeks) and/or after
      12 moths after birth. Data were also obtained from women's hospital delivery
      records. Descriptive statistical analysis was performed (survey and delivery
      data). Interview data were analysed using a seven-stage sequential form of
      qualitative analysis. RESULTS: Whilst many women supported the principle of
      choice, they identified how, in practice their autonomy was limited by individual
      circumstance and available care provision. All women felt that concerns about
      their baby's or their own health should take precedence over personal preference.
      Moreover, expressing a preference for either vaginal or caesarean birth was
      inherently problematic as choice until the time of delivery was neither static
      nor final. Women did not have autonomous choice over their actual birth method,
      but neither did they necessarily want it. CONCLUSIONS: The results of this large
      exploratory study suggest that choice may not be the best concept through which
      to approach the current arrangements for birth in the UK. Moreover, they
      challenge the notion of choice that currently prevails in international debates
      about caesarean delivery for maternal request.

PMID- 19385962
TI  - Treating miscarriages: a randomised study of cost-effectiveness in medical or
      surgical choice.
AB  - OBJECTIVE: The aim was to carry out a cost effectiveness analysis (CEA) of
      medical and surgical treatment of miscarriage using quantitative and qualitative
      indicators. DESIGN: A prospective study where the data of the clinical course of
      the treatment and the patients; experiences (pain and satisfaction) were
      collected from a previous randomised study. SETTING: Department of Obstetrics and
      Gynecology, Oulu University Hospital, Oulu, Finland. POPULATION: Ninety-eight
      eligible women with a diagnosed miscarriage. METHODS: The incremental cost
      effectiveness ratio (ICER) was calculated by using institutional prices
      (provider's aspect) of the medical care and the number of patients who
      experienced pain, dissatisfaction or unsuccessful treatment while treated for the
      miscarriage. MAIN OUTCOME MEASURES: Primary (uncomplicated treatment) and
      secondary (complications and other unplanned events) costs of the treatments.
      RESULTS: Primary costs of the surgical treatment were higher, but the more
      frequent unplanned events and complications in the medical group brought the
      costs to the same level. In the medical group, based on the ICER, 12 patients
      more experienced pain, 7 patients more were dissatisfied with the treatment and 5
      patients more had unsuccessful treatment compared with surgically treated
      patients. In theory, these negative outcomes could have been avoided by investing
      euro1688 more in the surgical treatment. CONCLUSIONS: Medical treatment of
      miscarriage was not more cost-effective, when the adverse events were considered.
      As neither of these two methods was economically superior, the treatment choice
      should be made on an individual basis by respecting the patient's choice.

PMID- 19385964
TI  - Women's views on the use of decision aids for decision making about the method of
      delivery following a previous caesarean section: qualitative interview study.
AB  - OBJECTIVE: To obtain the views of women on their experiences of decision making
      about the method of delivery following a previous caesarean section and the role
      of decision aids in this process. DESIGN: Qualitative study nested within a
      randomised controlled trial, using repeat semi-structured interviews conducted
      pre- and postnatally. Data were analysed using a framework approach. SETTING:
      Three maternity units in south-west England and Scotland. SAMPLE: Purposive
      sample of 30 women participating in a randomised controlled trial of two decision
      aids for women making a decision about mode of next delivery following a previous
      caesarean section (Decision Aids for Mode of next Delivery). RESULTS: Thirty
      women were interviewed during pregnancy about their experience of decision making
      about the mode of delivery and 22 were re-interviewed postnatally. Key themes
      were: role of decision aids in reducing decisional conflict and uncertainty
      during the pregnancy; impact of decision aids on knowledge and anxiety; the
      relationship between prior preferences, decisions and actual outcome; and the
      mediating role of decision aids. CONCLUSIONS: Women making a decision about mode
      of delivery following previous caesarean section value some form of structured
      information to help reduce decisional conflict. Information provision for women
      making this decision needs to be relevant to their individual needs. Decision
      analysis may help reconcile prior preferences and the actual mode of delivery.

PMID- 19385963
TI  - Occupational predictors of pregnancy outcomes in Irish working women in the
      Lifeways cohort.
AB  - OBJECTIVE: The objective of this study was to explore the association between
      occupational factors and pregnancy outcomes in a prospective cohort of Irish
      pregnant women. DESIGN: This study has a prospective design. POPULATION: The
      Lifeways cohort included 1124 pregnant women, 676 of whom delivered a single baby
      and were working at their first prenatal care visit when they filled in a self
      administered questionnaire. METHODS: Occupational factors were measured using
      this questionnaire and included eight factors describing job and working
      conditions. Data including pregnancy outcomes were also obtained from clinical
      hospital records. Logistic regression analysis was used to adjust for well-known
      risk factors. MAIN OUTCOME MEASURES: Birthweight (< or =3000 g and < or =2500 g),
      preterm delivery (<37 gestation weeks) and small-for-gestational-age. RESULTS:
      Significant associations were found between physical work demands and low
      birthweight (< or =2500 g) and working with between a temporary contract and
      preterm delivery. Trends were also observed between working 40 hours or more a
      week and shift work, and birthweight of 3000 g or less. The study of a cumulative
      index showed that being exposed to at least two of these occupational factors
      significantly predicted birthweight of < or =3000 g (OR = 2.44, 95% CI: 1.17
      5.08) and of < or =2500 g (OR = 4.65, 95% CI: 1.08-20.07) and preterm delivery
      (OR = 5.18, 95% CI: 1.00-27.01). CONCLUSIONS: Our findings suggest that
      occupational factors may predict birthweight through their predictive effects on
      preterm delivery. This is one of the few prospective studies on pregnancy
      outcomes that include working conditions. As they may be modifiable, occupational
      factors deserve more attention in relation to birth outcomes.

PMID- 19385965
TI  - Angiogenic growth factors in tissue homogenates of HNSCC: expression pattern,
      prognostic relevance, and interrelationships.
AB  - Head and neck squamous cell carcinoma has still a poor prognosis. Since
      angiogenesis is crucial for tumor growth, a better understanding of the potential
      clinical relevance as well as the interactions between the numerous proangiogenic
      growth factors is essential to develop improved therapeutic strategies in these
      tumors. Expression levels of eight growth factors known to induce angiogenesis
      (HGF, bFGF, VEGF-A, VEGF-D, PDGF-AB, PDGF-BB, G-CSF, and GM-CSF) were
      quantitatively measured by ELISA in homogenates of 41 head and neck squamous cell
      carcinomas. In addition, microvessel density and protein localization of growth
      factors were assessed by immunohistochemistry. Statistical analysis was performed
      to assess interrelationships between growth factors analyzed and to correlate
      protein levels with patient outcome. In 90% of the tissues at least 4/8 growth
      factors analyzed were detectable. Highest amounts and most frequent expression
      were found for HGF, bFGF and VEGF-A while PDGF-AB and PDGF-BB were present in two
      thirds and G-CSF and GM-CSF in approximately half of the cases. Although there
      was no significant relation to microvessel density, we identified significant
      associations for bFGF with HGF and G-CSF as well as of PDGF-AB with those of VEGF
      A and PDGF-BB. For the first time we demonstrate that expression levels of HGF as
      well as that of bFGF and G-CSF in head and neck squamous tumors are negative
      prognostic factors for patient survival. Our data indicate a network of
      interrelated and prognostically relevant growth factors in these tumors that have
      to be taken into consideration when planning an antiangiogenic and antitumor
      therapy.

PMID- 19385966
TI  - Pathogenetic significance of ecotropic viral integration site-1 in hematological
      malignancies.
AB  - The ecotropic viral integration site-1 (Evi-1) gene was first identified as a
      common locus of retroviral integration in murine leukemia models. In humans, EVI
      1 is located on chromosome 3q26, and rearrangements on chromosome 3q26 often
      activate EVI-1 expression in hematological malignancies. Overexpression of EVI-1
      also occurs with high frequency in leukemia patients without 3q26 abnormalities,
      and importantly, high EVI-1 expression is an independent negative prognostic
      indicator irrespective of the presence of 3q26 rearrangements. Recent gene
      targeting studies in mice revealed that Evi-1 is preferentially expressed in
      hematopoietic stem cells and plays an essential role in proliferation and
      maintenance of hematopoietic stem cells. In addition, intense attention has been
      focused on the EVI-1 gene complex as retrovirus integration sites because
      transcription-activating integrations into the EVI-1 locus confer survival and
      self-renewing ability to hematopoietic cells. The experimental results using
      animal models suggest that activation of Evi-1 in hematopoietic cells leads to
      clonal expansion or dysplastic hematopoiesis, whereas onset of full-blown
      leukemia requires cooperative genetic events. EVI-1 possesses diverse functions
      as an oncoprotein, including suppression of transforming growth factor-beta
      mediated growth inhibition, upregulation of GATA2, inhibition of the Jun kinase
      pathway, and stimulation of cell growth via activator protein-1. In this article,
      we summarize current knowledge regarding the biochemical properties and
      biological functions of EVI-1 in normal and malignant hematopoiesis, with
      specific focus on its pathogenetic significance in hematological malignancies.

PMID- 19385968
TI  - Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are
      characterized by negative estrogen receptor, positive human epidermal growth
      factor receptor type 2, and high Ki67 expression.
AB  - Recently, aldehyde dehydrogenase (ALDH) 1 has been identified as a reliable
      marker for breast cancer stem cells. The aim of our study was to investigate the
      clinicopathological characteristics of breast cancers with ALDH1+ cancer stem
      cells. In addition, the distribution of ALDH1+ tumor cells was compared on a cell
      by-cell basis with that of estrogen receptor (ER)+, Ki67+, or human epidermal
      growth factor receptor type 2 (HER2)+ tumor cells by means of double
      immunohistochemical staining. Immunohistochemical staining of ALDH1 was applied
      to 203 primary breast cancers, and the results were compared with various
      clinicopathological characteristics of breast cancers including tumor size,
      histological grade, lymph node metastases, lymphovascular invasion, ER,
      progesterone receptor, HER2, Ki67, and topoisomerase 2A as well as prognosis.
      Immunohistochemical double staining of ALDH1 and ER, Ki67, or HER2 was also
      carried out to investigate their distribution. Of the 203 breast cancers, 21
      (10%) were found to be ALDH1+, and these cancers were significantly more likely
      to be ER- (P = 0.004), progesterone receptor- (P = 0.025), HER2+ (P = 0.001),
      Ki67+ (P < 0.001), and topoisomerase 2A+ tumors (P = 0.012). Immunohistochemical
      double staining studies showed that ALDH1+ tumor cells were more likely to be ER
      , Ki67-, and HER2+ tumor cells. Patients with ALDH1 (score 3+) tumors showed a
      tendency (P = 0.056) toward a worse prognosis than did those with ALDH1- tumors.
      Breast cancers with ALDH1+ cancer stem cells posses biologically aggressive
      phenotypes that tend to have a poor prognosis, and ALDH1+ cancer stem cells are
      characterized by ER-, Ki67-, and HER2+.

PMID- 19385967
TI  - Cyclin E correlates with manganese superoxide dismutase expression and predicts
      survival in early breast cancer patients receiving adjuvant epirubicin-based
      chemotherapy.
AB  - Anthracycline-based chemotherapy represents a milestone in the treatment of
      breast cancer. We previously demonstrated in an in vitro model that cyclin E
      overexpression is associated with increased expression of manganese superoxide
      dismutase (MnSOD) and resistance to doxorubicin. In the present study,
      immunohistochemical expression of cyclin E and MnSOD was evaluated in 134 early
      breast cancer patients receiving adjuvant epirubicin-based chemotherapy regimens
      containing epirubicin. Both parameters were correlated with the available
      clinicopathological parameters and with the outcome of patients. Overexpression
      of cyclin E and MnSOD was detected in 46 (34.3%) and 56 (41.8%) patients,
      respectively, and expression levels of the two proteins were related. Disease
      free and alive patients displayed a lower mean percentage of cyclin E-expressing
      cells than relapsed and dead patients, respectively. Kaplan-Meier survival
      analysis demonstrated a significant separation between high versus low cyclin E
      expressing tumors in terms of overall survival (P = 0.038 by log-rank). Similar
      results were obtained considering the subset of node-negative patients
      separately. No significant relationship with patient outcome was observed for
      MnSOD expression levels. At multivariate analysis cyclin E failed to demonstrate
      an independent prognostic value. In conclusion, the results of the present study
      support previous evidence that increased cyclin E expression is associated with
      higher MnSOD expression levels and poorer outcome, at least as evaluated in terms
      of overall survival. Further studies are warranted to evaluate the usefulness of
      cyclin E as a prognostic marker to identify breast cancer patients at higher risk
      of death from the disease when treated with adjuvant anthracycline-based therapy.

PMID- 19385969
TI  - Cyclin-dependent kinase 1 inhibitor RO-3306 enhances p53-mediated Bax activation
      and mitochondrial apoptosis in AML.
AB  - Cyclin-dependent kinase (CDK) 1 and the murine double minute 2 homolog (MDM2)-p53
      interaction are potential therapeutic targets in cancer, and their inhibition has
      been reported to be more proapoptotic in malignant cells compared to normal
      cells. We investigated the effect of CDK1 inhibition on p53 signaling after
      simultaneous dual blockade using the CDK1 inhibitor RO-3306 and the MDM2
      inhibitor Nutlin-3 in AML. Treatment of growing AML cells with RO-3306 induced
      G2/M-phase cell cycle arrest and apoptosis in a dose- and time-dependent manner.
      We found that RO-3306 acts cooperatively with Nutlin-3 to induce mitochondrial
      apoptosis in a cell cycle-independent fashion. RO-3306 downregulated expression
      of the antiapoptotic proteins Bcl-2 and survivin and blocked p53-mediated
      induction of p21 and MDM2. CDK1 siRNA experiments showed that reduced CDK1
      expression affects p53-induced p21 transactivation. We suggest that RO-3306
      actively enhances downstream p53 signaling to promote apoptosis and that a
      combination strategy aimed at both inhibiting CDK1 and activating p53 signaling
      is potentially effective in AML, where TP53 mutations are rare and downstream p53
      signaling is intact.

PMID- 19385970
TI  - Personal use of hair dye and cancer risk in a prospective cohort of Chinese
      women.
AB  - Although widely studied over the past 40 years, personal use of hair dye
      generally has not been associated with overall cancer risk. The association
      between hair dye use and risk of bladder and hematopoietic cancers has been less
      conclusive. Most hair dye studies have been case-control studies conducted in
      Caucasian populations. We examined the relationship between personal hair dye use
      and cancer risk in a prospective cohort of 70,366 Chinese women. After an average
      of 7 years of follow up, 2437 women were newly diagnosed with cancer by 31
      December 2005. Cox proportional hazard models were used to estimate relative
      risks (RR) and 95% confidence intervals (CI) of cancer risk associated with hair
      dye use, adjusting for potential confounding factors. Compared with women who
      reported no hair dye use, ever users had an overall cancer risk of 0.89 (95% CI
      0.82, 0.97). No significant association was observed for several common cancers,
      including cancers of the breast (RR 0.93, 95% CI 0.78, 1.09), lung (RR 0.81, 95%
      CI 0.62, 1.09), stomach (RR 0.90, 95% CI 0.66, 1.21), and colorectum (RR 1.04,
      95% CI 0.84, 1.28). We also found no significant association with most other
      cancers, including bladder cancer (RR 1.14, 95% CI 0.56, 2.35) and hematopoietic
      cancers overall (RR 0.89, 95% CI 0.59, 1.35) or their subtypes, including non
      Hodgkin lymphoma, multiple myeloma, and leukemia. We generally found no evidence
      of an association between personal use of hair dye and cancer risk, although our
      study is limited by small numbers for certain cancer types.

PMID- 19385971
TI  - Both CD133+ and CD133- subpopulations of A549 and H446 cells contain cancer
      initiating cells.
AB  - Tumors have been known to contain a small population of cancer stem cells that
      initiate tumor growth and promote tumor spreading. CD133 alone or in combination
      with other markers is currently being used for identification and isolation of
      the putative cancer stem cell population from malignant tumors. To determine
      whether the CD133+ cells constitute the stem cell populations of lung cancer
      cells A549 and H446, CD133+ and CD133- subpopulations were sorted from A549 and
      H446 cells by magnetic cell separation and characterized for their in vitro stem
      cell-like properties. Interestingly, both the CD133+ and CD133- cells displayed
      similar abilities of colony formation, self-renewal, proliferation,
      differentiation, and invasion, as well as resistance to chemotherapy drugs.
      Furthermore, colony formation assays showed that more than 40% of cells in both
      the CD133+ cells and CD133- subpopulations could form large colonies capable of
      regenerating the unsorted populations and forming tumors in nude mice. These
      results suggest that CD133 alone cannot be used as a stem cell marker for the
      lung cancer cells A549 and H446, and both the CD133+ and CD133- subpopulations
      contain similar numbers of cancer stem cells.

PMID- 19385972
TI  - Vascular endothelial growth factor receptor 1 expression in pelvic lymph nodes
      predicts the risk of cancer progression after radical prostatectomy.
AB  - Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) 1
      positive hematopoietic progenitor cells precede the arrival of tumor cells and
      form clusters that may portend sites of future metastatic disease. The aim of the
      present study was to clarify whether VEGFR1 expression in pelvic lymph nodes
      predicts the risk of prostate cancer progression after radical prostatectomy.
      VEGFR1 expression in pelvic lymph nodes was examined by immunohistochemistry in
      95 patients who underwent radical prostatectomy for prostate cancer. A cluster of
      VEGFR1-positive cells was considered positive. Expression of VEGFR1 in pelvic
      lymph nodes and biochemical recurrence after radical prostatectomy were examined
      by univariate survival analysis and multivariate Cox proportional hazards
      regression analysis. Thirty-seven of 79 lymph node-negative patients (46.8%) were
      found to have VEGFR1-positive cells in their pelvic lymph nodes, whereas 16 of 16
      lymph node metastasis-positive patients (100%) had VEGFR1 clusters. There was a
      significant correlation between pathological stage and VEGFR1 staining (P =
      0.002). Univariate analysis showed that pathological stage > or = pT3 and VEGFR1
      expression in pelvic lymph nodes were each significantly associated with
      biochemical recurrence after radical prostatectomy. Multivariate analysis showed
      VEGFR1 expression to be an independent predictor of biochemical recurrence after
      radical prostatectomy (risk ratio = 5.715, P = 0.010), as was preoperative
      prostate-specific antigen (PSA) level > or = 10 ng/mL. Although larger validation
      studies are required, our results suggest that VEGFR1 expression in pelvic lymph
      nodes predicts the risk of biochemical PSA recurrence after radical
      prostatectomy.

PMID- 19385973
TI  - From tumor lymphangiogenesis to lymphvascular niche.
AB  - Metastasis in sentinel lymph nodes indicates the initial spread of tumors from a
      primary site. The recent discovery of tumor-associated growth of lymphatic
      vessels clarified that tumor lymphangiogenesis actively promotes enhanced
      draining/sentinel lymph node metastasis. Studies of experimental carcinogenesis
      have further established that tumors continue to induce lymphangiogenesis in
      metastatic foci such as draining lymph nodes. Lymphangiogenesis within draining
      lymph nodes probably contributes to enhanced distant lymph node and distant organ
      metastases. Lymph node lymphangiogenesis has recently been identified in several
      human malignancies, such as cutaneous malignant melanoma. Tumor-associated
      lymphangiogenesis thus has potential significance not only at the primary site,
      but also in lymph nodes. Primary tumors induce new lymphatic vessel growth in
      draining lymph nodes before metastasis. The remarkable enlargement of sinusoidal
      lymphatic endothelium might facilitate tumor cell transport to the lymph nodes,
      and potentially contribute to the migration, residence, and/or survival of
      metastatic tumor cancer stem cells by inducing a specific tumor microenvironment.
      Therefore, the novel concept of 'lymphvascular niche' is proposed herein to
      explain lymphatic network expansion. This concept might help to improve
      understanding of the molecular mechanism of lymph node metastasis, and change
      therapeutic approaches to treating cancer metastasis.

PMID- 19385975
TI  - Aberrant DNA methylation profile of hepatocellular carcinoma and surgically
      resected margin.
AB  - Field cancerization currently described the theory of tumorigenesis and, until
      now, has been described in almost all organ systems except in liver. For this
      reason, we explore the presence of field cancerization in liver and its
      underlying clinical implication in hepatocellular carcinoma (HCC). In our study,
      methylation profile of HCC and surgically resected margin (SRM) were established
      by methylation-specific PCR. Liver cirrhosis (LC), chronic hepatitis and normal
      liver were treated in the same way as the background control. The correlation
      analysis among the methylation profile of HCC, SRM and clinicopathological data
      of HCC patients was made respectively. Our results showed that methylation
      abnormities related to HCC, but not background disease existed in histologically
      negative SRM. Monoclonal and polyclonal models may coexist in field cancerization
      in liver. Patients with RIZ1 methylation in SRM had a shorter disease free
      survival. The local recurrence trend of early and later recurrence in HCC is
      potentially related to a second field tumor. From these results, we can suggest
      that field cancerization exists in liver. The study of field cancerization in
      liver plays an important role in hepatocarcinogenesis. Second field tumor derived
      form field cancerization may have important implications in HCC prognosis
      assessment that is worthy of further study.

PMID- 19385974
TI  - Antibodies to Helicobacter pylori and CagA protein are associated with the
      response to antibacterial therapy in patients with H. pylori-positive API2-MALT1
      negative gastric MALT lymphoma.
AB  - The aim of this study was to clarify predictive factors for response to
      eradication therapy in cases of Helicobacter pylori (H. pylori)-positive API2
      MALT1-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Sixty
      six patients who were examined for H. pylori infection and the presence of the
      API2-MALT1 chimeric transcript and who underwent H. pylori eradication therapy as
      first-line therapy, were enrolled in this study. Immunohistochemical markers
      (p53, Ki-67, and BCL10), microsatellite instability, loss of heterozygosity,
      serum levels of antibodies (anti-H. pylori and anti-CagA), and markers for
      gastritis (gastrin and pepsinogens) were examined, and the results were compared
      between patients whose tumors regressed completely after eradication therapy
      (responders) and patients whose tumors did not regress (non-responders). Of the
      66 patients with localized gastric MALT lymphoma, 47 (71.2%) showed complete
      remission after eradication therapy. None of the H. pylori-negative (n = 9)
      and/or API2-MALT1-positive (n = 7) patients responded to antibacterial treatment.
      Of 44 patients with H. pylori-positive API2-MALT1-negative gastric MALT lymphoma,
      38 (86.4%) showed complete remission after eradication therapy. Titers of
      antibodies against H. pylori and CagA protein were significantly higher in the
      responders than in the non-responders (P = 0.0235 and 0.0089, respectively). No
      significant difference between the groups was observed for the other factors. In
      conclusion, measurement of titers of serum antibodies to H. pylori and CagA
      protein may be useful for predicting the response to eradication therapy in
      patients with H. pylori-positive API2-MALT1-negative gastric MALT lymphoma.

PMID- 19385976
TI  - Prognostic implication of SYT-SSX fusion type and clinicopathological parameters
      for tumor-related death, recurrence, and metastasis in synovial sarcoma.
AB  - The present study aimed to describe the distribution and features of the SYT-SSX
      fusion gene in Chinese patients with synovial sarcoma (SS), and to analyze the
      prognostic value of SYT-SSX fusion type and clinicopathological parameters for
      tumor-related death, recurrence, and metastasis in SS. SYT-SSX1 and SYT-SSX2
      fusion transcripts were tested by reverse transcription-polymerase chain reaction
      in 141 formalin-fixed, paraffin-embedded SS. The prognostic implication of SYT
      SSX fusion type and clinicopathological parameters were analyzed by univariate
      and multivariate survival analyses. SYT-SSX1 and SYT-SSX2 were detected in 50
      (34.5%) and 91 (64.5%) tumors, respectively. SYT-SSX1 (risk ratio [RR] = 2.032, P
      = 0.004), larger tumor size (RR = 1.859, P = 0.008), and aggressive Federation
      Nationale des Centers de Lutte Contre le Cancer grade (RR = 2.094, P = 0.001)
      were adverse predictors for disease-specific survival. However, SYT-SSX fusion
      type was not associated with local recurrence-free survival (P = 0.216). Patients
      with larger tumors (RR = 2.071, P = 0.005) and those who received marginal
      excision (RR = 2.556, P = 0.005) had poor local recurrence-free survival.
      Besides, SYT-SSX1 (RR = 1.859, P = 0.037), older age (RR = 1.799, P = 0.040), and
      aggressive International Union Against Cancer stage (RR = 3.690, P < 0.001)
      proved to be adverse prognostic factors for metastasis-free survival. In
      conclusion, compared to SYT-SSX1, SYT-SSX2 was more frequent in Chinese patients
      with SS. Moreover, SYT-SSX1 was an adverse predictor for disease-specific
      survival and metastasis-free survival, but had no relation to local recurrence
      free survival. In addition, histological grade and tumor size were also important
      prognostic factors for SS.

PMID- 19385977
TI  - Islet enhancer vildagliptin: a powerful partner with metformin for the treatment
      of patients with type 2 diabetes.

PMID- 19385978
TI  - Metformin--the gold standard in type 2 diabetes: what does the evidence tell us?
AB  - Metformin is a cornerstone of oral antidiabetic treatment. Recent joint American
      and European guidelines recommend instituting metformin therapy along with
      lifestyle modification at the time type 2 diabetes mellitus (T2DM) is diagnosed.
      Metformin acts to reduce hepatic gluconeogenesis and improve glucose uptake, and
      it may exert protective effects on pancreatic islet cells. Although metformin
      therapy produces substantial reductions in HbA1c, it does not produce body weight
      gain, is not associated with substantial risk for hypoglycaemia and has neutral
      to positive effects on lipids and blood pressure. The major adverse events
      associated with metformin are gastrointestinal. T2DM progresses even with
      initially effective monotherapy, and most patients will therefore receive
      combination therapy. When selecting agents to coadminister with metformin, a
      physician must consider efficacy in glycaemic control, safety, tolerability and
      any effects that may compromise overall efficacy (e.g. effects on body weight,
      lipids or blood pressure). In this regard, incretin-based therapies have
      characteristics that make them particularly suitable for add-on therapy with
      metformin.

PMID- 19385979
TI  - The scientific evidence: vildagliptin and the benefits of islet enhancement.
AB  - Vildagliptin is an oral incretin enhancer that acts to increase active levels of
      the incretin hormone glucagon-like peptide-1 (GLP-1) by inhibiting the dipeptidyl
      peptidase-4 enzyme responsible for the rapid deactivation of GLP-1 in vivo. This
      activity results in improved glucose-dependent functioning of pancreatic islet
      beta and alpha cells, addressing two central deficits in type 2 diabetes mellitus
      (T2DM). Vildagliptin treatment improves beta-cell sensitivity to glucose,
      producing increased insulin secretory rate relative to glucose in both
      postprandial and fasting states. Improved alpha-cell function is shown as
      restoration of appropriate glucose-related suppression of glucagon and,
      therefore, reduced endogenous glucose production during both postprandial and
      fasting periods. There is evidence that long-term vildagliptin treatment may slow
      underlying deterioration of beta-cell function in T2DM. There is also a potential
      synergistic effect of vildagliptin and metformin in increasing active GLP-1
      levels, and this activity may contribute to the long-term improvements in beta
      cell function observed in patients with T2DM who have vildagliptin added to
      ongoing metformin therapy. Vildagliptin treatment has also been associated with
      beneficial extrapancreatic effects, including improved peripheral insulin
      sensitivity and improved postprandial triglyceride-rich lipoprotein metabolism.
      Improvement of beta- and alpha-cell function through incretin enhancement with
      vildagliptin results in more physiologic meal-related and fasting glycaemia
      profiles.

PMID- 19385980
TI  - Translating science into clinical practice: focus on vildagliptin in combination
      with metformin.
AB  - Vildagliptin is a potent and selective oral dipeptidyl peptidase-4 inhibitor that
      improves glycaemic control in patients with type 2 diabetes mellitus (T2DM) by
      increasing both alpha- and beta-cell responsiveness to glucose. The efficacy,
      tolerability and safety of the combination of vildagliptin and metformin in the
      treatment of T2DM have been established in numerous trials in the extensive
      vildagliptin clinical programme. As add-on therapy in patients with inadequate
      glycaemic control on metformin, vildagliptin produces clinically significant
      reductions in glycated haemoglobin (HbA1c) and fasting plasma glucose, is well
      tolerated, and is associated with absence of weight gain and minimal risk of
      hypoglycaemia. Compared with thiazolidinedione add-on treatment, vildagliptin is
      associated with similar significant reductions in HbA1c without the weight gain
      seen with the former. Compared with sulfonylurea add-on treatment, vildagliptin
      is associated with similar efficacy in controlling glycaemia but absence of
      weight gain and a markedly lower risk of hypoglycaemia. In drug-naive patients,
      single-tablet combinations of vildagliptin/metformin 50/500 and 50/1000 mg bid
      produced significantly greater reductions in HbA1c than monotherapy with either
      agent and were well tolerated, with no weight gain and minimal risk of
      hypoglycaemia. The combination of vildagliptin and metformin poses numerous
      advantages in the treatment of T2DM.

PMID- 19385981
TI  - Raising the bar for acceptance; new length restrictions on Epilepsia manuscripts.

PMID- 19385982
TI  - Hippocampal Nabeta3 expression in patients with temporal lobe epilepsy.
AB  - Voltage-dependent sodium channels consist of a pore-forming alpha-subunit and
      regulatory beta-subunits. Alterations in these channels have been implicated in
      temporal lobe epilepsy (TLE) and several genetic epilepsy syndromes. Recently we
      identified Na(v)beta3 as a TLE-regulated gene. Here we performed a detailed
      analysis of the hippocampal expression of Na(v)beta3 in TLE patients with
      hippocampal sclerosis (HS) and without HS (non-HS) and compared expression with
      autopsy controls (ACs). Immunoblot analysis showed that Na(v)beta3 levels were
      dramatically reduced in the hippocampus, but not in the cortex of non-HS patients
      when compared to HS patients. This was confirmed by immunohistochemistry showing
      reduced Na(v)beta3 expression in all principal neurons of the hippocampus proper.
      Sequence analysis revealed no Na(v)beta3 mutations. The functional consequences
      of the reduced Na(v)beta3 expression in non-HS patients are unknown. Altered
      Na(v)beta3 expression might influence microcircuitry in the hippocampus,
      affecting excitability and contributing to epileptogenesis in non-HS patients.
      Further experiments are required to elucidate these functional possibilities.

PMID- 19385983
TI  - Ventricular asystole during vagal nerve stimulation.

PMID- 19385984
TI  - Recurrent lamotrigine-induced aseptic meningitis.

PMID- 19385987
TI  - Results of risk-adapted therapy in acute myeloid leukaemia. A long-term
      population-based follow-up study.
AB  - In 1997-2003, a protocol for treatment of acute myeloid leukaemia (AML) (except
      promyelocytic leukaemia) was activated in four Swedish health care regions
      covering 50% of the national population. Based on cytogenetics and clinical
      findings, patients aged 18-60 yr were assigned to one of three risk groups. In
      this report we account for the long-term clinical outcome of enrolled patients.
      Patients received idarubicin and cytarabine in standard doses as induction
      therapy and consolidation courses included high-dose cytarabine. Allogeneic stem
      cell transplantation (allo-SCT) from an human leucocyte antigen-identical sibling
      was recommended in standard and poor-risk patients, whereas unrelated donor
      transplant was reserved for poor-risk patients. Autologous (auto-SCT) was
      optional for standard or poor risk patients not eligible for allo-SCT. Two
      hundred seventy-nine patients with de novo or secondary (9%) AML, median age 51
      (18-60) yr, corresponding to 77% of all patients in the population, were
      included. Twenty (7%) patients were assigned to the good risk group, whereas 150
      (54%) and 109 patients (39%) were assigned to standard- and poor-risk groups,
      respectively. Induction failures accounted for 55 patients; 16 early deaths eight
      of whom had white blood cell (WBC) >100 at diagnosis, and 39 refractory disease.
      Thus, complete remission (CR) rate was 80%. At study closure, the median follow
      up time of living patients was 90 months. Median survival time from diagnosis in
      the whole group was 27 months and 4-yr overall survival (OS) rate was 44%. In
      good, standard, and poor risk groups, 4-yr OS rates were 60, 57 and 24%,
      respectively. Median relapse-free survival (RFS) time in CR1 was 25 months and
      RFS at 4 yr was 44%. Four-year RFS rates were significantly (P < 0.001) different
      between the three risk groups; 64% in good risk, 51% in standard risk and 27% in
      poor risk patients. One hundred-ten transplantations were performed in CR1; 74
      allo-SCT (50 sibling, 24 unrelated donor), and 36 auto-SCT. Non-relapse mortality
      was 16% for allo-SCT patients. Outcome after relapse was poor with median time to
      death 163 d and 4-yr survival rate 17%. Three conclusions were: (i) these data
      reflect treatment results in a minimally selected population-based cohort of
      adult AML patients <60 yr old; (ii) a risk-adapted therapy aiming at early
      allogeneic SCT in patients with a high risk of relapse is hampered by induction
      deaths, refractory disease, and early relapses; and (iii) high WBC count at
      diagnosis is confirmed as a strong risk factor for early death but not for
      relapse.

PMID- 19385988
TI  - Neuronal substrates of gaze following in monkeys.
AB  - Human and non-human primates follow the gaze of their respective conspecific to
      identify objects of common interest. Whereas humans rely on eye-gaze for such
      purposes, monkeys preferentially use head-gaze information. Functional magnetic
      resonance imaging (fMRI) studies have delineated an area in the human superior
      temporal sulcus (STS), which is specifically activated when subjects actively
      follow the eye-gaze of others. Similarly, using fMRI, we have identified an
      analogous region in the monkey's middle STS responding to gaze following. Hence,
      although humans and monkeys might rely on different directional cues guiding
      their attention, they seem to deploy a similar and possibly homologous cortical
      area to follow the gaze of a conspecific. Our results support the idea that the
      eyes developed a new social function in human evolution, most likely to support
      cooperative mutual social interactions building on a phylogenetically old STS
      module for the processing of head cues.

PMID- 19385989
TI  - Differential loss and preservation of glutamate receptor function in bipolar
      cells in the rd10 mouse model of retinitis pigmentosa.
AB  - Photoreceptor degenerations can trigger morphological alterations in second-order
      neurons, however, the functional implications of such changes are not well known.
      We conducted a longitudinal study, using whole-cell patch-clamp,
      immunohistochemistry and electron microscopy to correlate physiological with
      anatomical changes in bipolar cells of the rd10 mouse - a model of autosomal
      recessive retinitis pigmentosa. Rod bipolar cells (RBCs) showed progressive
      changes in mGluR6-induced currents with advancing rod photoreceptor degeneration.
      Significant changes in response amplitude and kinetics were observed as early as
      postnatal day (P)20, and by P45 the response amplitudes were reduced by 91%, and
      then remained relatively stable until 6 months. These functional changes
      correlated with the loss of rod photoreceptors and mGluR6 receptor expression.
      Moreover, we showed that RBCs make transient ectopic connections with cones
      during progression of the disease. At P45, ON-cone bipolar cells (ON-CBCs) retain
      mGluR6 responses for longer periods than the RBCs, but by about 6 months these
      cells also strongly downregulate mGluR6 expression. We propose that the relative
      longevity of mGluR6 responses in CBCs is due to the slower loss of the cones. In
      contrast, ionotropic glutamate receptor expression and function in OFF-CBCs
      remains normal at 6 months despite the loss of synaptic input from cones. Thus,
      glutamate receptor expression is differentially regulated in bipolar cells, with
      the metabotropic receptors being absolutely dependent on synaptic input. These
      findings define the temporal window over which bipolar cells may be receptive to
      photoreceptor repair or replacement.

PMID- 19385991
TI  - Learning to filter out visual distractors.
AB  - When learning to master a visual task in a cluttered natural environment, it is
      important to optimize the processing of task-relevant information and to
      efficiently filter out distractors. However, the mechanisms that suppress task
      irrelevant information are not well understood. Here we show that training leads
      to a selective increase in motion coherence detection thresholds for task
      irrelevant motion directions that interfered with the processing of task-relevant
      directions during training. Furthermore, using functional magnetic resonance
      imaging we found that training attenuated neural responses associated with the
      task-irrelevant direction compared with the task-relevant direction in the visual
      cortical areas involved in processing of visual motion. The strongest suppression
      of functional magnetic resonance imaging responses to task-irrelevant motion
      information was observed in human area MT+. These findings reveal that perceptual
      learning leads to the suppression and efficient filtering of task-irrelevant
      visual information.

PMID- 19385990
TI  - Comparing the role of the anterior cingulate cortex and 6-hydroxydopamine nucleus
      accumbens lesions on operant effort-based decision making.
AB  - Both the anterior cingulate cortex (ACC) and mesolimbic dopamine, particularly in
      the nucleus accumbens (NAc), have been implicated in allowing an animal to
      overcome effort constraints to obtain greater benefits. However, their exact
      contribution to such decisions has, to date, never been directly compared. To
      investigate this issue we tested rats on an operant effort-related cost-benefit
      decision-making task where animals selected between two response alternatives,
      one of which involved investing effort by lever pressing on a high fixed-ratio
      (FR) schedule to gain high reward [four food pellets (HR)], whereas the other led
      to a small amount of food on an FR schedule entailing less energetic cost [two
      food pellets, low reward (LR)]. All animals initially preferred to put in work to
      gain the HR. Systemic administration of a D2 antagonist caused a significant
      switch in choices towards the LR option. Similarly, post-operatively, excitotoxic
      ACC lesions caused a significant bias away from HR choices compared with sham
      lesioned animals. There was no slowing in the speed of lever pressing and no
      correlation between time to complete the FR requirement and choice performance.
      Unexpectedly, no such alteration in choice allocation was observed in animals
      following 6-hydroxydopamine NAc lesions. However, these rats were consistently
      slower to initiate responding when cued to commence each trial and also showed a
      reduction in food hoarding on a species-typical foraging task. Taken together,
      this implies that only ACC lesions, and not 6-hydroxydopamine NAc lesions as
      performed here, cause a bias away from investing effort for greater reward when
      choosing between competing options

PMID- 19385992
TI  - Alpha2 nicotine receptors function as a molecular switch to continuously excite a
      subset of interneurons in rat hippocampal circuits.
AB  - Rapid activation of nicotinic acetylcholine receptors (nAChRs) at various
      anatomical and cellular locations in the hippocampus differentially modulates the
      operation of hippocampal circuits. However, it is largely unknown how the
      continued presence of nicotine affects the normal operation of hippocampal
      circuits. Here, we used single and dual whole-cell recordings to address this
      question. We found that horizontally oriented interneurons in the stratum
      oriens/alveus continuously discharged action potentials in the presence of
      nicotine. In these interneurons, bath application of nicotine produced slow
      inward currents that were well maintained and inhibited by the non-alpha 7
      antagonist dihydro-beta-erythroidine. Single-cell reverse transcription
      polymerase chain reaction analysis showed that nicotine-responding interneurons
      were consistently positive for the alpha2 subunit mRNA. These observations
      suggest that in the presence of nicotine, a subset of interneurons in the stratum
      oriens/alveus are continuously excited due to the sustained activation of alpha2*
      nAChRs. These interneurons were synaptically connected to pyramidal cells, and
      nicotine increased inhibitory baseline currents at the synapses and suppressed
      phasic inhibition at the same synapses. Nicotine-induced inhibitory activity
      increased background noise and masked small phasic inhibition in pyramidal cells,
      originating from other interneurons in the stratum radiatum. Thus, the continued
      presence of nicotine alters the normal operation of hippocampal circuits by
      gating inhibitory circuits through activating a non-desensitizing alpha2 nAChR
      subtype on a distinct population of interneurons.

PMID- 19385993
TI  - Substance P and cocaine employ convergent mechanisms to depress excitatory
      synaptic transmission in the rat nucleus accumbens in vitro.
AB  - Substance P (SP) has been reported to produce effects on excitatory synaptic
      transmission in the nucleus accumbens (NAc) that are similar to those induced by
      cocaine. To address the question of whether SP serves as an endogenous mediator
      producing cocaine-like effects that are known to be D1-receptor-mediated, we
      tested the hypothesis that the effects of SP and cocaine on excitatory
      postsynaptic currents (EPSCs) in the NAc occlude one another. We report here that
      SP and SP(5-11) actions occlude the effect of cocaine and vice versa. SP, SP(5
      11) and cocaine all depressed evoked, non-N-methyl-D-aspartate (NMDA) receptor
      mediated synaptic currents in a concentration-dependent manner, with EC50 values
      of 0.12, 0.17 and 8.3 microm, respectively. Although cocaine was the least
      potent, it was most efficacious. SP, SP(5-11) and cocaine all suppressed isolated
      NMDA receptor-mediated evoked EPSCs. SP(5-11) (1 microm)-induced EPSC depression
      was blocked by the neurokinin-1 antagonist L732138 and by the D1-like receptor
      antagonist SCH23390. Pretreatment of slices with cocaine (30 microm) depressed
      the EPSC by 39.1% +/- 4.8%. Application of SP or SP(5-11) (1 microm) at the peak
      of the cocaine depressive effect on the EPSC did not produce any additional
      diminution of the response (5.7% +/- 2.8%). In the reverse experiments, in which
      either SP or SP(5-11) was applied first, subsequent application of cocaine at the
      peak of the peptide's effect (30.3% +/- 2.3%) produced a further but smaller
      depression (15.5% +/- 3.6%) of the remaining EPSC. These data indicate that
      cocaine and SP produce similar effects on excitatory synaptic transmission in the
      NAc, and that their actions occlude one another. This suggests that SP may act
      like cocaine in its absence, and may be an endogenous trigger for the reward and
      behaviors associated with cocaine.

PMID- 19385994
TI  - Cholesterol-dependent attachment of human respiratory cells by Bordetella
      pertussis.
AB  - Bordetella pertussis is a re-emerging human respiratory pathogen whose infectious
      process is not fully understood, hampering the design of effective vaccines. The
      nature of bacterial attachment to host cells is a key event in the outcome of the
      infection. However, host cell receptors involved in B. pertussis colonization of
      the respiratory tract are still under investigation. Here, we report that
      cholesterol-rich domains are involved in B. pertussis adhesion to epithelial
      cells. Treatment of A549 cells with cholesterol-sequestering drugs such as methyl
      beta-cyclodextrin, nystatin, or filipin resulted in a significant decrease of B.
      pertussis attachment. Confocal laser microscopy studies showed B. pertussis
      associated with cholesterol-rich domains. Accordingly, B. pertussis was found in
      detergent-resistant membrane domain fractions isolated from bacterial-infected
      A549 cells. Our results indicate a main role of filamentous hemagglutinin, an
      environmentally regulated virulence factor, in this interaction, and a specific
      affinity for cholesterol, one of the major components of tracheal secretions,
      which might additionally contribute to the effective colonization of the
      respiratory tract.

PMID- 19385995
TI  - Influence of antibiotic exposure in the early postnatal period on the development
      of intestinal microbiota.
AB  - The influence of antibiotic exposure in the early postnatal period on the
      development of intestinal microbiota was monitored in 26 infants including five
      antibiotic-treated (AT) subjects orally administered a broad-spectrum antibiotic
      for the first 4 days of life and three caesarean-delivered (CD) subjects whose
      mothers were intravenously injected by the similar type of antibiotics in the
      same period. The faecal bacterial composition was analysed daily for the first 5
      days and monthly for the first 2 months. Terminal restriction fragment length
      polymorphisms in the AT subjects showed less diversity with the attenuation of
      the colonization of some bacterial groups, especially in Bifidobacterium and
      unusual colonization of Enterococcus in the first week than the control
      antibiotic-free infants (AF, n=18). Quantitative real-time PCR showed overgrowth
      of enterococci (day 3, P=0.01; day 5, P=0.003; month 1, P=0.01) and arrested
      growth of Bifidobacterium (day 3, P=0.03) in the AT group. Furthermore, after 1
      month, the Enterobacteriaceae population was markedly higher in the AT group than
      in the AF group (month 1, P=0.02; month 2, P=0.02). CD infants sustained similar,
      although relatively weaker, alteration in the developing microbiota. These
      results indicate that antibiotic exposure at the beginning of life greatly
      influences the development of neonatal intestinal microbiota.

PMID- 19385996
TI  - DNA repair in Mycobacterium tuberculosis revisited.
AB  - Our understanding of Mycobacterium tuberculosis DNA repair mechanisms is still
      poor compared with that of other bacterial organisms. However, the publication of
      the first complete M. tuberculosis genome sequence 10 years ago boosted the study
      of DNA repair systems in this organism. A first step in the elucidation of M.
      tuberculosis DNA repair mechanisms was taken by Mizrahi and Andersen, who
      identified homologs of genes involved in the reversal or repair of DNA damage in
      Escherichia coli and related organisms. Genes required for nucleotide excision
      repair, base excision repair, recombination, and SOS repair and mutagenesis were
      identified. Notably, no homologs of genes involved in mismatch repair were
      identified. Novel characteristics of the M. tuberculosis DNA repair machinery
      have been found over the last decade, such as nonhomologous end joining, the
      presence of Mpg, ERCC3 and Hlr - proteins previously presumed to be produced
      exclusively in mammalian cells - and the recently discovered bifunctional dCTP
      deaminase:dUTPase. The study of these systems is important to develop therapeutic
      agents that can counteract M. tuberculosis evolutionary changes and to prevent
      adaptive events resulting in antibiotic resistance. This review summarizes our
      current understanding of the M. tuberculosis DNA repair system.

PMID- 19385997
TI  - Differentiation of Debaryomyces hansenii and Candida famata by rRNA gene
      intergenic spacer fingerprinting and reassessment of phylogenetic relationships
      among D. hansenii, C. famata, D. fabryi, C. flareri (=D. subglobosus) and D.
      prosopidis: description of D. vietnamensis sp. nov. closely related to D.
      nepalensis.
AB  - The intergenic spacer rDNA amplification and AluI fingerprinting (IGSAF) method
      detected four distinct groups among 170 Debaryomyces hansenii strains: D.
      hansenii var. hansenii; Candida famata var. famata; D. hansenii var. fabryi and
      C. famata var. flareri. IGS sequence comparison of representative strains showed
      that D. hansenii var. hansenii and C. famata var. famata belonged to one species,
      whereas D. hansenii var. fabryi and C. famata var. flareri belonged to two
      different ones. This confirmed the following three species recently reinstated:
      D. hansenii (=C. famata), Debaryomyces fabryi and Debaryomyces subglobosus
      (=Candida flareri). Accordingly, growth at 37 degrees C may no longer be used to
      differentiate D. hansenii from D. fabryi. Riboflavin production is more specific
      for D. fabryi and D. subglobosus strains. IGSAF identified all the other 17
      species of the genus Debaryomyces, six of them sharing with D. hansenii an rRNA
      gene unit harbouring two 5S rRNA genes. The phylogenetic tree established with
      IGS sequences was congruent with the one based on ACT1, GPD1 and COX2 sequences
      depicting a distinct D. hansenii clade close to the D. subglobosus, Debaryomyces
      prosopidis and D. fabryi clade. Description of Debaryomyces vietnamensis sp. nov.
      (type strain CBS 10535(T), MUCL 51648(T)), closely related to Debaryomyces
      nepalensis is given.

PMID- 19385999
TI  - Space maintenance.
AB  - OBJECTIVE: The use of a space maintainer appliance, or restoration of a carious
      primary tooth that can then act as a natural space maintainer, may potentially
      obviate the consequences of loss of arch length and the need for complex
      orthodontic treatment at a later stage. Nevertheless, all space maintainer
      appliances are plaque retentive and may predispose to dental caries and gingival
      inflammation. Space maintainer appliances may also impinge on the soft tissues,
      interfere with eruption of adjacent teeth, fracture, and become dislodged or
      lost. This review article provides a summary of the available evidence, and
      considers the indications for space maintenance. METHODS: Medline and Ovid
      Medline were scanned, and additionally a hand-search of non-listed peer-reviewed
      papers written in English was performed. A total of 16 pertinent papers published
      between 1987 and 2007 that satisfied the inclusion criteria were selected for
      discussion. CONCLUSIONS: There is limited evidence to recommend either for or
      against the use of space maintainers to prevent or reduce the severity of
      malocclusion in the permanent dentition. Decisions regarding the use of space
      maintainers should be guided by balancing the occlusal disturbance that may
      result if one is not used against the potential plaque accumulation and caries
      that the appliance may cause.

PMID- 19385998
TI  - Dynamics of in vitro acquisition of resistance by Candida parapsilosis to
      different azoles.
AB  - Candida parapsilosis is a common isolate from clinical fungal infectious
      episodes. Resistance of C. parapsilosis to azoles has been increasingly reported.
      To analyse the development of resistance in C. parapsilosis, four azole
      susceptible clinical strains and one American Type Culture Collection type strain
      were cultured in the presence of fluconazole, voriconazole and posaconazole at
      different concentrations. The isolates developed variable degrees of azole
      resistance according to the antifungal used. Fluconazole was the fastest inducer
      while posaconazole was the slowest. Fluconazole and voriconazole induced
      resistance to themselves and each other, but not to posaconazole. Posaconazole
      induced resistance to all azoles. Developed resistance was stable; it could be
      confirmed after 30 days of subculture in drug-free medium. Azole-resistant
      isolates revealed a homogeneous population structure; the role of azole
      transporter efflux pumps was minor after evaluation by microdilution and
      cytometric assays with efflux pump blockers (verapamil, ibuprofen and carbonyl
      cyanide 3-chloro-phenylhydrazone). We conclude that the rapid development of
      azole resistance occurs by a mechanism that might involve mutation of genes
      responsible for ergosterol biosynthesis pathway, stressed by exposure to
      antifungals.

PMID- 19386002
TI  - Symmorphosis and livestock bioenergetics: production animal muscle has low
      mitochondrial volume fractions.
AB  - A comparative analysis of skeletal muscle structure reveals that production
      species (nine species, representing three mammalian families and an avian family)
      have mitochondrial volume fractions (MVF) 37% lower than the non-production
      species at equivalent size (17 species, with representatives from 10 mammalian
      families) (Fig. 1; F(1,25) = 4.79; p = 0.039). As MVF provides evidence of
      oxidative capacity, this comparative analysis indicates that production animals
      share an exceptionally low oxidative capacity muscle phenotype. A possible
      bioenergetic reason for this observation, relating to a reduction in the cost of
      maintaining trans-membrane ion gradients is briefly discussed. This discussion is
      framed within a biological economic design theory called symmorphosis and makes
      predictions about avenues for improvements in livestock bioenergetics.

PMID- 19386003
TI  - Daily pattern of some fatty acids in the athletic horse.
AB  - In the sport field, non-esterified fatty acids (NEFA) are important for the
      physical performance during the aerobic exercise of short intensity and long
      duration. In man, rat, goat and in the sedentary horse studies on the
      chronometabolism showed the presence of a circadian rhythm of the plasmatic
      concentration of NEFA while data for the athletic horse are lacking. To define a
      chronogram helpful for a specific planning and the differentiation of the
      training programmme in the athletic horse, the circadian pattern of some fatty
      acids (NEFA, palmitic, stearic, oleic, linoleic and linolenic acids) was studied
      in five Sella Italiana horses. These horses trained following a daily model of
      activity consisting of walk, trot, gallop and jump of obstacles of different
      heights. Blood samples were collected from the jugular vein every 4 h, starting
      at 08:00 hours, for 2 days to assess the concentrations of total NEFA (by
      spectrophotometry), palmitic, stearic, oleic, linoleic and linolenic acids (by
      gas chromatography). anova for repeated measures showed a statistical significant
      effect of the time of the day in NEFA, oleic and linolenic acids. The application
      of the periodic model showed the periodic pattern of NEFA, oleic, linoleic and
      linolenic acids. Acrophases were in the afternoon for all parameters. The results
      obtained showed a different trend of the circadian pattern of the studied
      parameters in the athletic horse than in the sedentary one because the physical
      activity and the post-prandial metabolism acted as zeitgebers.

PMID- 19386004
TI  - Effect of dietary alpha-tocopherol + ascorbic acid, selenium, and iron on
      oxidative stress in sub-yearling Chinook salmon (Oncorhynchus tshawytscha
      Walbaum).
AB  - A three-variable central composite design coupled with surface-response analysis
      was used to examine the effects of dietary alpha-tocopherol + ascorbic acid
      (TOCAA), selenium (Se), and iron (Fe) on indices of oxidative stress in juvenile
      spring Chinook salmon. Each dietary factor was tested at five levels for a total
      of fifteen dietary combinations (diets). Oxidative damage in liver and kidney
      (lipid peroxidation, protein carbonyls) and erythrocytes (erythrocyte resistance
      to peroxidative lysis, ERPL) was determined after feeding experimental diets for
      16 (early December) and 28 (early March) weeks. Only TOCAA influenced oxidative
      stress in this study, with most measures of oxidative damage decreasing (liver
      lipid peroxidation in December and March; ERPL in December; liver protein
      carbonyl in March) with increasing levels of TOCAA. We also observed a TOCAA
      stimulated increase in susceptibility of erythrocytes to peroxidative lysis in
      March at the highest levels of TOCAA. The data suggest that under most
      circumstances a progressive decrease in oxidative stress occurs as dietary TOCAA
      increases, but higher TOCAA concentrations can stimulate oxidative damage in some
      situations. Higher levels of TOCAA in the diet were required in March than in
      December to achieve comparable levels of protection against oxidative damage,
      which may have been due to physiological changes associated with the parr-smolt
      transformation. Erythrocytes appeared to be more sensitive to variation in
      dietary levels of TOCAA than liver and kidney tissues. Using the March ERPL assay
      results as a baseline, a TOCAA level of approximately 350-600 mg/kg diet would
      provide adequate protection against lipid peroxidation under most circumstances
      in juvenile Chinook salmon.

PMID- 19386005
TI  - The effect of vitamin C supplementation in healthy dogs on antioxidative capacity
      and immune parameters.
AB  - The aim of the study was to investigate the ability of vitamin C to increase the
      antioxidative and immunomodulating potential in healthy dogs. Fifteen dogs were
      tested for the effects of orally administered vitamin E (60 mg dl-alpha
      tocopheryl acetate) in combination with vitamin C (0, 30 or 60 mg ascorbic acid
      crystalline). Three treatments (0, 30, 60 mg vitamin C) were tested in a 3 x 3
      cross-over study in three periods of 36 days. Pre-prandial blood samples were
      taken for analysis of vitamins C, E, A, retinyl palmitate and stearate,
      antioxidant status [Thiobarbituric acid reactive substances (TBARS) and uric
      acid], biochemical and haematological analysis. Subpopulations of lymphocytes,
      mitogen-induced peripheral blood mononuclear cell proliferation (PBMC) and serum
      IgA and IgG concentrations were determined. There was a trend (p = 0.056) for an
      increased plasma vitamin C concentration by vitamin C supplementation. There was
      no evidence that dietary treatment altered neither the other plasma vitamin
      concentrations nor TBARS and uric acid concentrations nor the subpopulations of
      the lymphocytes except for the number of CD4+ lymphocytes that increased with
      vitamin C supplementation. There was no effect of vitamin C on serum IgA and IgG
      concentration. A significant time x treatment interaction was demonstrated on
      PBMC's to pokeweed, with an increase observed by 30 mg vitamin C supplementation
      but a decrease by 60 mg vitamin C supplementation. There was no clear evidence
      for an effect of dietary vitamin C on antioxidative capacity in healthy dogs fed
      a diet with vitamin E concentrations well above the recommendations. Yet, a
      limited number of immunological parameters were slightly affected.

PMID- 19386006
TI  - Comparison of the fast-induced and high dietary zinc-induced molting: trace
      elements dynamic in serum and eggs at different production stages in hens (Gallus
      domesticus).
AB  - A number of 252, 70 week old, single comb white leghorn hens at the end of their
      first production cycle were divided into two groups: group-I; molted by fasting
      and group-II; by high dietary zinc to obtain the second and third production
      cycle. Sampling was carried out at 5%, peak and end of the second production
      cycle and at 5% and peak of the third production cycle. Serum zinc decreased at
      the peak of the second production cycle, while increased at the 5% of the third
      production cycle in zinc-molted group. Serum copper and manganese increased at
      the 5% and peak of the second production cycle in zinc-molted group. Egg albumin
      zinc and copper increased at the 5% and peak of the second as well as third
      production cycles in zinc-molted group. Egg albumin manganese increased at 5%
      during the second production cycle in fasting molted group. Egg yolk zinc
      increased at the peak of the second production cycle in zinc-molted group. Egg
      yolk copper increased at the 5% of second production cycle but decreased during
      the third production cycle in zinc-molted group. Egg yolk manganese increased at
      the 5% and at the end of the second production cycle in zinc molted group. Egg
      yolk manganese and iron decreased during the third production cycle in zinc
      molted group. Eggshell zinc decreased at the end of the second production cycle
      in the zinc-molted group, while eggshell copper increased at the peak of the
      second as well as third production cycles in fasting molted group.

PMID- 19386007
TI  - Nutritive defaunation of the rumen in steers with subsequent refaunation using a
      cryopreserved monoculture of Entodinium caudatum.
AB  - This study evaluated a technique for the nutritive defaunation of the rumen of
      cattle with subsequent single species refaunation using a cryopreserved
      monoculture of Entodinium caudatum (family Ophryoscolecidae). Four mature steers
      were nutritionally defaunated in two periods using two steers in each period. A
      diet containing (dry matter basis) 68% ground wheat grain, 7% wheat bran, 8%
      soybean oil and 17% wheat straw was used to decrease the pH of ruminal contents
      and to eliminate rumen ciliate protozoa. Protozoa-free rumens were observed on
      day 8 and 9 in the first and second period, respectively, after the start of
      defaunation. A monoculture of E. caudatum (34/89/94) was transported from the
      Institute of Animal Physiology, Slovak Academy of Sciences in Kosice to the
      University of Kiel (Germany) in liquid nitrogen in October 1996. The inoculation
      was accomplished on day 15 in the second period by applying 30 ml culture medium
      with a monoculture of E. caudatum (34/89/94; average concentration of protozoal
      cells 2 650/ml) into the rumen of a defaunated steer via the ruminal fistula. The
      mono-faunated steer was successfully inoculated with an average concentration of
      E. caudatum cells at 4.1 x 10(3)/ml (SD = 0.2) on day 2 after the inoculation.

PMID- 19386008
TI  - Optimizing the sensory characteristics and acceptance of canned cat food: use of
      a human taste panel.
AB  - A methodology based on descriptive analysis techniques used in the evaluation of
      human food has been successfully refined to allow for a human taste panel to
      profile the flavour and texture of a range of cat food products (CFP) and their
      component parts. Included in this method is the development of evaluation
      protocols for homogeneous products and for binary samples containing both meat
      chunk (MC) and gravy/gel (GG) constituents. Using these techniques, 18 flavour
      attributes (sweet, sour/acid, tuna, herbal, spicy, soy, salty, cereal, caramel,
      chicken, methionine, vegetable, offaly, meaty, burnt flavour, prawn, rancid and
      bitter) and four texture dimensions (hardness, chewiness, grittiness and
      viscosity) were generated to describe the sensations elicited by 13 commercial
      pet food samples. These samples differed in intensity for 16 of the 18 flavour
      attributes, which allows for individual CFP flavour profiles to be developed.
      Principal components analysis (PCA) could successfully discriminate between
      samples within the PCA space and also reveal some groupings amongst them. While
      many flavour attributes were weakly correlated, a large number (describing both
      taste and retro-nasal aroma qualities) were required to adequately differentiate
      between samples, suggesting considerable complexity in the products assessed. For
      both MC and GG, differences between samples for each of the texture dimensions
      were also found. For MC, grittiness appears to be the most discriminating
      textural attribute, while for GG viscosity discriminates well between samples.
      Meat chunks and gravy/gels differed significantly from each other in both flavour
      and texture. Cat food products differed in their liking ratings, although no
      differences were found between homogeneous, MC and GG samples, and eight flavour
      attributes were correlated with overall liking scores. It is now necessary to
      determine the usefulness and limits of sensory data gathered from human panels in
      describing and predicting food acceptance and preference behaviours in cats. For
      instance, while the sense of taste in cats appears generally similar to that of
      other mammals, they lack a sweet taste receptor (Li et al., 2006), which may
      limit the applicability of sweetness ratings obtained from humans. Modification
      of existing techniques used with human food research, such as external preference
      mapping (Naes and Risvik, 1996) may be useful. Ultimately, this may facilitate
      more economical and efficient methods for optimizing cat food flavour and texture
      and predicting the effects of composition and processing changes on cat feeding
      behaviour. This will require collaboration between pet food manufacturers and
      nutritionists, animal behaviourists and human sensory scientists. The results of
      this preliminary study should assist in this process.

PMID- 19386009
TI  - High methanogenic potential of sucrose compared with starch at high ruminal pH.
AB  - The role of ruminal pH with respect to the expression of a differentiation in the
      methanogenic potential of easily fermentable carbohydrates was determined using
      the rumen simulation technique. The target pH at 21 h after feed supply was set
      to 6.0 and 7.0 through a specific buffer management. A basal diet was
      supplemented with crystalline sucrose or steamflaked maize starch. With sucrose
      instead of starch, the decline in fermenter fluid pH, 4 h after introducing new
      feed, was more pronounced at both buffer levels, and degradability of all
      nutrients, including fibre was higher too. At low pH, molar propionate proportion
      was higher with sucrose. Methane quantity depended on the combination of pH and
      source of easily fermentable carbohydrate as sucrose, compared with starch,
      enhanced methanogenesis (+40%), but only at the high pH. The concomitant increase
      in organic matter degradability with sucrose at high target pH did not completely
      explain this phenomenon, as the effects on methane were still significant when
      related to apparently fermented organic matter. However, differences caused by pH
      and carbohydrate type decreased when methane was related to degraded fibre,
      suggesting that there was a mutual supportive effect of high pH and sucrose on
      fibre degradation.

PMID- 19386010
TI  - Use of gene profiling to evaluate the effects of a feed additive on immune
      function in periparturient dairy cattle.
AB  - Objectives were to investigate mechanisms by which a nutritional supplement
      alters immunity in dairy cattle. Our hypothesis was that feeding this product to
      dairy cattle altered neutrophil gene expression. Eight periparturient Jersey
      cattle were randomly assigned to one of two treatments: control and treated.
      Control animals were fed a dry cow ration for 1 month prior to calving. The
      treated cows were fed the same ration supplemented with OmniGen-AF. Following
      calving, blood samples were taken and neutrophils were prepared after which RNA
      was extracted. Gene expression in neutrophils of treated versus control-fed
      animals was then assessed using bovine-total leukocyte (BOTL-5) arrays. Eighteen
      genes were differentially regulated in the experimental group and of these, twice
      as many were up-regulated as down-regulated. Patterns of changes indicated that
      the additive might alter neutrophil apoptosis, signaling and sensitivity. Two of
      the regulated genes [interleukin-1beta converting enzyme (ICE) and interleukin-4
      receptor (IL-4R)] were investigated in more detail using quantitative reverse
      transcriptase-polymerase chain reaction (QRT-PCR). Each was found to be elevated
      by the feeding of experimental product. Increased expression of ICE indicates
      potential for enhanced neutrophil expression of interleukin-1beta (IL-1beta), a
      cytokine which plays roles in the inflammatory response and which stimulates
      adaptive immunity following innate immune activation. Altered expression of IL-4R
      indicates potential for changes in neutrophil apoptosis. The experiment
      identified mechanisms by which the additive altered neutrophil gene expression.
      While many nutrients support the immune system, we have shown that a non
      traditional nutritional approach may also have utility in modulating immune
      function.

PMID- 19386011
TI  - Histological and immunohistochemical evaluation of duodenal and colonic biopsies
      after oral bovine lactoferrin supplementation in beagle puppies.
AB  - Lactoferrin is a natural compound in the milk of mammals and was shown to
      influence the intestinal micro-flora and the immune system in mice, calves, dogs
      and man. The present study was carried out to investigate the effect of orally
      administered bovine lactoferrin (0, 30, 60 and 120 mg/kg DM feed) on the
      intestinal morphology and lymphocyte colonization in 36 motherless raised
      puppies. Endoscopic biopsies from duodenum and colon, taken in week 14, were
      scored histologically after staining with haematoxylin and eosin (H&E) and
      lymphocytes (CD3+, CD4+, CD8+) and plasma cells (IgA+, IgG+, IgM+) were
      enumerated after immunohistochemical staining by computer-aided quantification.
      Histological scoring revealed no significant differences amongst the groups. IgG+
      plasma cells were reduced (p < 0.05) in the lamina propria of the colon of the 30
      and the 60 mg group. The number of CD8+ lymphocytes was higher (p < 0.05) in the
      epithelium of the colon of the lactoferrin groups. In conclusion, this study
      indicated only minimal effects of bovine lactoferrin on the population of
      selected immune cells in the gut mucosa of puppies. More investigations are
      needed to describe the impact of lactoferrin on the digestive physiology of
      puppies.

PMID- 19386012
TI  - Beta-carotene is incorporated or mobilized along with triglycerides in bovine
      adipose tissue in response to insulin or epinephrine.
AB  - Pasture fed cattle ingest substantial amounts of beta-carotene (beta-C). Not all
      of the carotenoid compound is transformed into vitamin A, but the surplus is
      deposited in adipose tissue (AT). The mechanisms of beta-C incorporation and
      mobilization are unknown. Two experiments were conducted using explants from
      bovine AT cultured in vitro. First, beta-C incorporation by explants from three
      animals was examined with different beta-C concentrations (0, 1, 5 and 20 microm)
      and different times of incubation (every 5 h up to 25 h). The data showed a
      significant increase of beta-C concentration in explants only for 20 microm beta
      C. Secondly, effects of insulin and epinephrine on beta-C and triglyceride (TG)
      contents of explants were studied. Explants from six animals were incubated with
      either hormone and 0 or 20 microm beta-C for 20 h. Both TG and beta-C contents
      were affected positively by insulin and negatively by epinephrine. Interestingly,
      changes in ratios of beta-C/TG (hormone vs. control) were similar (1.7 x 10(-3)
      and 1.8 x 10(-3)), respectively, for insulin and epinephrine, indicating that
      beta-C level is directly related to TG content. We also report the presence of
      mRNA for beta-C 15, 15' oxygenase in bovine AT. The in vitro culture system using
      explants from bovine AT is a promising model to investigate factors that might
      affect the accumulation and metabolism of beta-C.

PMID- 19386013
TI  - Feeding value of enset (Ensete ventricosum), Desmodium intortum hay and untreated
      or urea and calcium oxide treated wheat straw for sheep.
AB  - Feed intake, in vivo nutrient digestibility and nitrogen utilization were
      evaluated in male sheep fed different fractions (leaf, pseudostem, corm, whole
      plant) of enset, untreated or 2% urea- and 3% calcium oxide- (CaO or lime)
      treated wheat straw and Desmodium intortum hay as sole diets. All feeds, except
      D. intortum hay and enset leaf had low crude protein (CP) content. Non-fiber
      carbohydrate contents were higher in enset fractions, especially in pseudostem
      and corm relative to other feeds. Enset leaf and pseudostem had high calcium,
      phosphorus and manganese contents. Corm, whole enset and D. intortum hay were
      rich sources of zinc. Daily dry matter and CP intakes were higher (p < 0.05) in
      sheep fed D. intortum hay (830 and 133 g, respectively) than those fed pseudostem
      (92 and 7.8 g, respectively). Organic matter digestibilities were highest for
      corm (0.780) and whole enset (0.776) and lowest for D. intortum hay (0.534) and
      untreated wheat straw (0.522). The CP digestibility ranged from 0.636 in D.
      intortum hay to 0.408 in corm. Nitrogen (N) balance was highest (p < 0.05) in D.
      intortum hay (10.4 g/day) and lowest in corm (-1.3 g/day). Enset leaf could be a
      useful protein supplement whereas the pseudostem and corm could be good sources
      of energy.

PMID- 19386014
TI  - Indication of intracellular magnesium deficiency in lactating dairy cows revealed
      by magnesium loading and renal fractional excretion.
AB  - Nine non-pregnant, lactating dairy cows were used to study plasma and urinary
      magnesium concentrations ([Mg]pl; [Mg]u), and the urinary fractional excretion of
      magnesium (FE(Mg)) before, during and after an 120 min intravenous magnesium (Mg)
      administration (2.5 mg/kg body weight). Animals received a total mixed ration,
      and Mg content of the diet was within recommended range. Basal mean [Mg]pl, [Mg]u
      and FE(Mg) were 0.89 +/- 0.09 mm, 5.92 +/- 2.99 mm and 8.3 +/- 9.7% respectively.
      For all parameters, a substantial inter-individual variation was observed. Three
      cows showed suboptimal [Mg]pl and/or [Mg]u as well as low FE(Mg) values of
      approximately 2% indicating an insufficient Mg supply to these animals (depressed
      feed intake, reduced absorption of Mg). The applied Mg challenge induced no
      significant change of mean [Mg]pl in the cows because part of the excess Mg was
      excreted in the urine. But in five out of nine cows, a decrease of the FE(Mg),
      during and after an intravenous Mg load was observed showing that part of the
      infused Mg is used to replenish intracellular Mg pools. Thus, the existence of an
      intracellular Mg deficiency in these cows was unmasked by performing the Mg
      loading test only. Because a reduced free intracellular [Mg] impairs cell and
      tissue functions, the results highlight the importance of an accurate definition
      of the intracellular Mg status. The Mg loading test is a suitable procedure,
      however, for practical purposes less expensive and time consuming methods must be
      developed.

PMID- 19386015
TI  - Dietary protein concentration affects intestinal microbiota of adult cats: a
      study using DGGE and qPCR to evaluate differences in microbial populations in the
      feline gastrointestinal tract.
AB  - The objective of this study was to identify qualitative and quantitative
      differences in microbial populations of adult cats fed diets containing different
      protein concentrations. Following a 4 week baseline period, eight healthy adult
      domestic short-hair queens (>1-year-old) were randomly allotted to a moderate
      protein (MP; n = 4) or high-protein (HP; n = 4) diet for 8 weeks. Fresh faecal
      samples were collected after baseline and 8 weeks on treatment and stored at -80
      degrees C. Following DNA extraction, samples were analyzed using denaturing
      gradient gel electrophoresis to distinguish qualitative changes between diets.
      Quantitative polymerase chain reaction was used to measure E. coli,
      Bifidobacterium, Clostridium perfringens, and Lactobacillus populations. Compared
      to baseline, cats fed MP had a bacterial similarity index of 66.7% as opposed to
      40.6% similarity for those fed HP, exhibiting marked changes in intestinal
      bacteria of cats fed HP. Bifidobacterium populations were greater (p < 0.05) in
      cats fed MP versus HP (9.44 vs. 5.63 CFU/g). Clostridium perfringens populations
      were greater (p < 0.05) in cats fed HP than MP (12.39 vs. 10.83 CFU/g). In this
      experiment, a high-protein diet resulted in a dramatic shift in microbial
      populations. Decreased Bifidobacterium population in cats fed HP may justify
      prebiotic supplementation for such diets.

PMID- 19386016
TI  - Influence of rumen escape starch on pancreatic exocrine secretion of goats.
AB  - The objective of the experiment was to evaluate the effect of rumen escape starch
      (RES), accomplished by altering dietary starch concentrations on pancreatic
      exocrine secretion of goats. Four goats (36.8 +/- 3.2 kg) with common bile duct
      re-entrant and duodenal catheters were used in a 4 x 4 Latin square. Goats were
      fed diets containing 20%, 30%, 40% and 50% starch. Periods consisted of 10 day
      adaptation followed by 3 day of sample collection. Juice was collected in 1-h
      fractions continuously for 72 h. Total juice secreted was recorded, and 3% sub
      samples were retained to form a composite sample. The remaining fluid was
      returned to the duodenum. Juice composite samples were analyzed for activities of
      alpha-amylase, trypsin, chymotrypsin and lipase. Secretion of pancreatic alpha
      amylase was lower (p < 0.05) when comparing lambs fed 20% starch diet with 30%,
      40% and 50% starch diets. Lipase secretion was greater (p < 0.05) in lambs fed
      40% starch diet compared with the other diets. Total secretion of juice, trypsin
      and chymotrypin was not affected (p > 0.05) by dietary starch concentration.
      Rumen escape starch increased with increasing dietary starch concentration (p <
      0.05). Regression analysis showed that increasing RES results in a quadratic
      increase (p < 0.05) in pancreatic alpha-amylase and lipase secretion, and the
      secretion of alpha-amylase and lipase is maximum when RES is 113 and 83 g/day
      respectively. These results suggest that optimal RES for pancreatic secretion of
      alpha-amylase and lipase is 80-110 g/day in adult goats.

PMID- 19386018
TI  - Phototoxic and photoallergic reactions.

PMID- 19386017
TI  - Effects of fermentable carbohydrates and low dietary phosphorus supply on the
      chemical composition of faecal bacteria and microbial metabolites in the
      gastrointestinal tract of pigs.
AB  - The objective was to determine the effects of fermentable carbohydrates on
      phosphorus (P) metabolism, the chemical composition of the faecal mixed bacterial
      mass (MBM) and the microbial activity in the large intestine (LI) of pigs. Eight
      barrows (mean BW 35.9 +/- 0.9 kg), fitted with simple T-cannulas at the terminal
      ileum, were either fed a low-P corn-soybean meal-based control diet or 75% of the
      control diet supplemented with 25% cellulose, starch or pectin according to a 4 x
      3 Latin Square design. Both pectin and cellulose caused higher faecal than ileal
      P recoveries. Ileal volatile fatty acids (VFA) levels were more pronounced for
      the starch (p < 0.05) rather than the cellulose and pectin treatments, whereas
      pectin resulted in a higher faecal VFA concentration in comparison to starch and
      cellulose (p < 0.05). The differences in faecal VFA concentrations corresponded
      to the pH values obtained in faeces. The N content of MBM was higher (p < 0.05)
      when cellulose was supplemented. Pectin caused a decrease in the P content of the
      MBM compared to the control (p < 0.05). As a result, the N:P ratio was
      significantly higher for the pectin (N:P = 4.33) than for the control treatment
      (N:P = 2.63), while the Ca:P ratio remained constant for all treatments,
      suggesting changes in the accumulation of N, P and Ca in MBM, probably due to
      changes in the species composition and activity of the microflora.

PMID- 19386019
TI  - Off-label use in dermatology in Germany: what has changed since 2004.
AB  - Off-label use is defined as the usage of pharmaceuticals beyond their submitted,
      tested and approved use. Not only indications but also doses, route of
      administration, patients' characteristics and concomitant therapies are affected
      by the approval. In recent years, the impact of off-label use has increased
      markedly primarily because of the large number of new medications with often
      limited approval. In dermatology, a multitude of diagnoses exist which are so
      uncommon that they have no chance of approval studies. Experiences of off-label
      use often provide important scientific data that can influence or even improve
      further concepts of therapy. Both professional liability and mode of payment are
      still controversial for medications in off-label use. There is an urgent need for
      more legal certainty in use of off-label medication to guarantee maximum safety
      for patients and medical staff. Both professional societies and funding agencies
      should work together to resolve this problem.

PMID- 19386020
TI  - Changes in quality of life for patients with chronic venous insufficiency,
      present or healed leg ulcers.
AB  - BACKGROUND: Patients with chronic leg ulcers are handicapped in daily life, both
      by physical complaints and social problems. The aim of our study was not only to
      assess a possible impairment of quality of life (QOL) of leg ulcer patients but
      also to evaluate if there is a real improvement of QOL after healing of the
      ulcer. Patients with chronic venous insufficiency served as the control group. We
      further analyzed if there were significant differences in the response between
      patients who were and were not performing compression therapy. PATIENTS AND
      METHOD: We interviewed three groups of patients (active venous leg ulcer, healed
      venous leg ulcer and patients with chronic venous insufficiency using the
      "Freiburger Life Quality Assessment fur Venenerkrankungen" (FLQAv). RESULTS:
      Physical problems, daily handicaps and social problems all increased with age.
      Contrary to our expectations, healing of a leg ulcer did not lead to a
      significant increase in QOL. Instead, patients with active ulcers did not regard
      their QOL as lower than those in the other groups. Compression therapy also did
      not impair QOL in the three groups. CONCLUSION: Even though ulcer healing is an
      admirable goal, it does not necessarily lead to an improved QOL, probably because
      of the numerous comorbidities in this patient group. Nonetheless, it is important
      to control problems associated directly with the wound to allow ulcer patients to
      participate actively in everyday life and minimize social problems.

PMID- 19386021
TI  - Sensitization to para-amino compounds in swim fins in a 10-year-old boy.
AB  - A ten-year-old boy presented with recurrent eczema on the dorsal of both feet and
      the thighs. His symptoms became worse when he used racing swim fins. Patch
      testing included the standard, ointments, preservatives, leather, textile dyes,
      rubber component, and corticosteroid series of the German Contact Dermatitis
      Research Group (DKG) as well as the patient's own materials (fin material). At 72
      hours positive reactions were observed to blue flipper material, Acid Yellow 36,
      Bismarck Brown R, and DPPD. DPPD is widely used as an antioxidant in the rubber
      industries. Therefore, the dermatitis was most probably attributable to DPPD in
      the blue flipper material, although we were not able to prove this due to lack of
      cooperation of the manufacturer. Sensitization to Acid Yellow 36 and Bismarck
      Brown R are interpreted as cross sensitizations, since all substances are para
      amino compounds.

PMID- 19386022
TI  - Non-infectious inflammatory disorders of the nail apparatus.
AB  - Inflammatory non-infectious diseases of the nails are not uncommon. The nail
      changes may look different in the same diseases, but also very much alike in
      various different nail disorders depending on which particular structure of the
      nail apparatus is involved. Of all skin diseases, psoriasis is the one with the
      most frequent nail involvement. The presence of many pits allows the diagnosis to
      be made, but salmon spots and onycholysis are also characteristic features.
      Lichen planus may occur isolated on the nails or in association with lesions of
      the skin and adjacent mucosal membranes. Longitudinal striations and loss of the
      nail plate shine are the most frequent features of nail lichen planus. The more
      severe the alopecia areata is and the younger the patient is, the more often it
      affects the nail, usually with a rough surface and loss of shine. Eczemas and
      various autoimmune dermatoses may also affect the nails but the changes are not
      clinically specific.

PMID- 19386023
TI  - Pain: basics and relevance in dermatology.
AB  - Scientific progress in pathophysiology and differentiation of pain, functional
      diagnostic of pain and emerging treatments highlight this subject. Basics of
      development of pain, as well as differentiation of nociceptive and neuropathic
      pain are depicted; the latter is illustrated with the example of postherpetic
      neuralgia. Complex regional pain syndromes are described as a third pain complex.
      Principles of differentiated pain management are given. Substance groups from the
      WHO scheme including antipyretic analgesics, non-steroidal antiinflammatory drugs
      (NSAIDs) and opioids are discussed. Recommendations of the Drug Commission of the
      German Medical Association concerning NSAIDs and of the International Association
      for the Study of Pain (IASP) concerning new treatment options for cancer pain are
      cited. Overviews amongst others from the Cochrane library for local anesthetics,
      opioids and for the treatment of postherpetic neuralgia are included. Tables are
      provided to simplify use in daily practice. The goal of this overview is a
      conceptual development of pain diagnosis and therapy in dermatology.

PMID- 19386024
TI  - Melatonin reduces induction of Bax, caspase and cell death in methamphetamine
      treated human neuroblastoma SH-SY5Y cultured cells.
AB  - Several studies demonstrated that methamphetamine (MA)-treated human
      neuroblastoma cells exhibit increased oxidative stress, which regulates
      intracellular signaling cascades leading to cell death. Melatonin has a potential
      as a direct free radical scavenger and protects against cell death caused by MA.
      The objective of this study was to investigate the neuroprotective properties of
      melatonin on MA-induced induction of death signaling cascade and neuronal cell
      degeneration in human neuroblastoma SH-SY5Y cultured cells. The results of the
      present study demonstrate that MA significantly reduced cell viability in SH-SY5Y
      cultured cells. Desipramine, a monoamine uptake blocker, and melatonin reversed
      the toxic effect of MA in reducing cell viability. Induction of Bax, Bcl-2 and
      cleaved caspase-3 protein levels were observed in SH-SY5Y cultured cells treated
      with MA, whereas the induction of Bax and cleaved caspase-3 was diminished by
      melatonin. Visualization of the induction of Bax using immunofluorescence but a
      reduction in mitochondrial sites using red-fluorescent mitochondria-staining dye
      was more obviously apparent in MA-treated cells than in untreated control cells
      and, again, this effect was abolished by melatonin. These findings demonstrate
      important roles of Bax and caspase in death signaling cascade, and the protective
      effects of melatonin in MA-treated SH-SY5Y cells.

PMID- 19386025
TI  - Outcomes of transjugular intrahepatic portosystemic shunt through the left branch
      vs. the right branch of the portal vein in advanced cirrhosis: a randomized
      trial.
AB  - BACKGROUND/AIMS: The transjugular intrahepatic portosystemic shunt (TIPS) is
      technically divided into TIPS through the left branch of the portal vein (TIPS
      LBPV) and TIPS through the right branch of the portal vein (TIPS-RBPV). In order
      to compare their advantages and disadvantages, this randomized, controlled trial
      was designed to investigate their outcomes in advanced cirrhotic patients.
      METHODS: Seventy-two patients were randomly placed into TIPS-LBPV (36 patients)
      and TIPS-RBPV (36 patients, with four failures) groups, and they were
      prospectively followed for 2 years after TIPS implantation. RESULTS: Patients who
      underwent the two different kinds of TIPS were balanced during recruitment for
      this study. The incidences of overall encephalopathy and de novo encephalopathy
      in the TIPS-LBPV group were significantly lower than that of the TIPS-RBPV group
      during follow-up (P=0.036 and 0.012 respectively). The incidences of rebleeding
      or re-intervention and improvement of ascites were similar between groups
      (P>0.05). Patients undergoing TIPS-RBPV required more rehospitalization and
      incurred more costs than those who underwent TIPS-LBPV (P=0.030 and 0.039
      respectively). There was no significant difference between the two groups in
      survival based on a survival curve constructed according to the Kaplan-Meier
      method (P>0.05). CONCLUSION: Patients undergoing TIPS-LBPV had a lower incidence
      of encephalopathy, less rehospitalization and lower costs after TIPS implantation
      compared with patients undergoing TIPS-RBPV.

PMID- 19386026
TI  - Telmisartan attenuates progression of steatohepatitis in mice: role of hepatic
      macrophage infiltration and effects on adipose tissue.
AB  - BACKGROUND/AIMS: Non-alcoholic fatty liver disease and non-alcoholic
      steatohepatitis (NASH) are the hepatic manifestation of metabolic syndrome.
      However, its therapeutic strategy has not been established. Recently, an
      angiotensin II type 1 receptor blocker, telmisartan (Tel), has received a great
      deal of attention as a therapeutic tool for metabolic syndrome. The aim of this
      study was to investigate the efficacy and mechanisms of Tel on a murine NASH
      model. METHODS: C57BL/6 mice were fed a methionine- and choline-deficient high
      fat diet (MCDHF) or a standard diet with/without the administration of Tel (10
      mg/kg/day) for 8 weeks. RESULTS: MCDHF feeding induced marked steatohepatitis
      with macrophage infiltration. Tel attenuated liver steatosis with decreased
      hepatic triglycerides (P<0.05) and fibrogenesis with decreased type I collagen
      and transforming growth factor-beta1 mRNA expressions (P<0.05). Tel also
      suppressed the infiltration of macrophages into the liver and decreased hepatic
      monocyte chemoattractant protein-1 and its receptor (CC-chemokine receptor 2;
      CCR2) mRNA expressions, especially CCR2. In vitro, Tel suppressed CCR2
      expression, which was induced by low-density lipoprotein. The size of adipocyte
      in visceral fat tissue was reduced with an increased serum adiponectin
      concentration in the Tel group. CONCLUSIONS: In this study, we revealed that Tel
      attenuated steatohepatitis progression by suppressing the macrophage infiltration
      into the liver. Tel also affected the reduction of adipocyte size and elevation
      of serum adiponectin. Tel might serve as a new therapeutic strategy for NASH.

PMID- 19386027
TI  - Superoxide anions and hydrogen peroxide inhibit proliferation of activated rat
      stellate cells and induce different modes of cell death.
AB  - BACKGROUND: In chronic liver injury, hepatic stellate cells (HSCs) proliferate
      and produce excessive amounts of connective tissue causing liver fibrosis and
      cirrhosis. Oxidative stress has been implicated as a driving force of HSC
      activation and proliferation, although contradictory results have been described.
      AIM: To determine the effects of oxidative stress on activated HSC proliferation,
      survival and signalling pathways. METHODS: Serum-starved culture-activated rat
      HSCs were exposed to the superoxide anion donor menadione (5-25 micromol/L) or
      hydrogen peroxide (0.2-5 mmol/L). Haem oxygenase-1 mRNA expression, glutathione
      status, cell death, phosphorylation of mitogen-activated protein (MAP) kinases
      and proliferation were investigated. RESULTS: Menadione induced apoptosis in a
      dose- and time-dependent, but caspase-independent manner. Hydrogen peroxide
      induced necrosis only at extremely high concentrations. Both menadione and
      hydrogen peroxide activated Jun N-terminal kinase (JNK) and p38. Hydrogen
      peroxide also activated extracellular signal-regulated protein. Menadione, but
      not hydrogen peroxide, reduced cellular glutathione levels. Inhibition of JNK or
      supplementation of glutathione reduced menadione-induced apoptosis. Non-toxic
      concentrations of menadione or hydrogen peroxide inhibited platelet-derived
      growth factor- or/and serum-induced proliferation. CONCLUSION: Reactive oxygen
      species (ROS) inhibit HSC proliferation and promote HSC cell death in vitro.
      Different ROS induce different modes of cell death. Superoxide anion-induced HSC
      apoptosis is dependent on JNK activation and glutathione status.

PMID- 19386028
TI  - The energy balance equation: looking back and looking forward are two very
      different views.
AB  - The energy balance equation has served as an important tool for the study of
      bioenergetics. It is based on one of the most fundamental properties of
      thermodynamics and has been invaluable in understanding the interactions of
      energy intake, energy expenditure, and body composition. Recently, however, the
      obesity epidemic has extended the use of the equation to the creation of public
      health messages for preventing or even reversing secular trends in body mass
      index. This usage often fails to consider how changes in any one term of the
      equation can lead to accommodations in one or both of the other two terms. It is
      concluded that research and public health messages should not simply consider how
      interventions affect just energy expenditure or energy intake, but rather how
      they affect the balance or gap between energy intake and expenditure.

PMID- 19386029
TI  - Vegetarian and vegan diets in type 2 diabetes management.
AB  - Vegetarian and vegan diets offer significant benefits for diabetes management. In
      observational studies, individuals following vegetarian diets are about half as
      likely to develop diabetes, compared with non-vegetarians. In clinical trials in
      individuals with type 2 diabetes, low-fat vegan diets improve glycemic control to
      a greater extent than conventional diabetes diets. Although this effect is
      primarily attributable to greater weight loss, evidence also suggests that
      reduced intake of saturated fats and high-glycemic-index foods, increased intake
      of dietary fiber and vegetable protein, reduced intramyocellular lipid
      concentrations, and decreased iron stores mediate the influence of plant-based
      diets on glycemia. Vegetarian and vegan diets also improve plasma lipid
      concentrations and have been shown to reverse atherosclerosis progression. In
      clinical studies, the reported acceptability of vegetarian and vegan diets is
      comparable to other therapeutic regimens. The presently available literature
      indicates that vegetarian and vegan diets present potential advantages for the
      management of type 2 diabetes.

PMID- 19386030
TI  - Funding food science and nutrition research: financial conflicts and scientific
      integrity.
AB  - There has been significant public debate about the susceptibility of research to
      biases of various kinds. The dialogue has extended to the peer-reviewed
      literature, scientific conferences, the mass media, government advisory bodies,
      and beyond. While biases can come from myriad sources, the overwhelming focus of
      the discussion, to date, has been on industry-funded science. Given the critical
      role that industry has played and will continue to play in the research process,
      the International Life Sciences Institute (ILSI) North America Working Group on
      Guiding Principles has, in this paper, set out proposed conflict-of-interest
      guidelines, regarding industry funding, for protecting the integrity and
      credibility of the scientific record, particularly with respect to health,
      nutrition, and food-safety science. Eight principles are enumerated, specifying
      ground rules for industry-sponsored research. The paper, which issues a challenge
      to the broader scientific community to address all bias issues, is only a first
      step; the document is intended to be dynamic, prompting ongoing discussion and
      refinement. The Guiding Principles are as follows. In the conduct of
      public/private research relationships, all relevant parties shall: 1) conduct or
      sponsor research that is factual, transparent, and designed objectively;
      according to accepted principles of scientific inquiry, the research design will
      generate an appropriately phrased hypothesis and the research will answer the
      appropriate questions, rather than favor a particular outcome; 2) require control
      of both study design and research itself to remain with scientific investigators;
      3) not offer or accept remuneration geared to the outcome of a research project;
      4) prior to the commencement of studies, ensure that there is a written agreement
      that the investigative team has the freedom and obligation to attempt to publish
      the findings within some specified time-frame; 5) require, in publications and
      conference presentations, full signed disclosure of all financial interests; 6)
      not participate in undisclosed paid authorship arrangements in industry-sponsored
      publications or presentations; 7) guarantee accessibility to all data and control
      of statistical analysis by investigators and appropriate auditors/reviewers; and
      8) require that academic researchers, when they work in contract research
      organizations (CRO) or act as contract researchers, make clear statements of
      their affiliation; require that such researchers publish only under the auspices
      of the CRO.

PMID- 19386031
TI  - Fatty acids and cardiovascular disease.
AB  - Fatty acids have been classified into "good" or "bad" groups according to their
      degree of unsaturation or whether they are "animal fat" or "vegetable fat".
      Today, it appears that the effects of fatty acids are complex and vary greatly
      according to the dose and the nature of the molecule. Monounsaturated fatty acids
      are still considered as having a "neutral" status, but any benefits may be
      related to the chemical environment of the source food or the associated overall
      food pattern. Controversy surrounds omega-6 polyunsaturated fatty acids, because
      even though they lower LDL cholesterol levels, excessive intakes do not appear to
      be correlated with cardiovascular benefit. The omega-3 fatty acids are known to
      exert cardiovascular protective effects. Dairy fat and its cardiovascular impact
      are being evaluated. This review examines the existing literature on the
      relationships between the different fatty acids and cardiovascular disease.

PMID- 19386032
TI  - Into the matrix: regulation of the iron regulatory hormone hepcidin by matriptase
      2.
AB  - Matriptase-2 is a recently identified membrane-bound, cell-surface serine
      protease expressed primarily in liver. Mutations in matriptase-2 in mice and
      humans cause iron-deficiency anemia that responds poorly to iron therapy. The
      poor response results from an inability to decrease hepcidin production during
      iron deficiency. Cell culture studies reveal that matriptase-2 inhibits hepcidin
      induction by cleaving membrane hemojuvelin, a potent activator of hepcidin
      transcription. As a novel suppressor of hepcidin expression, matriptase-2 emerges
      as a possible candidate for therapeutic interventions aimed at treating disorders
      of iron metabolism.

PMID- 19386033
TI  - Vitamin D and tuberculosis.
AB  - Tuberculosis is highly prevalent worldwide, accounting for nearly two million
      deaths annually. Vitamin D influences the immune response to tuberculosis, and
      vitamin D deficiency has been associated with increased tuberculosis risk in
      different populations. Genetic variability may influence host susceptibility to
      developing active tuberculosis and treatment response. Studies examining the
      association between genetic polymorphisms, particularly the gene coding for the
      vitamin D receptor (VDR), and TB susceptibility and treatment response are
      inconclusive. However, sufficient evidence is available to warrant larger
      epidemiologic studies that should aim to identify possible interactions between
      VDR polymorphisms and vitamin D status.

PMID- 19386035
TI  - Out of the Andes: patterns of diversification in clearwing butterflies.
AB  - Global biodiversity peaks in the tropical forests of the Andes, a striking
      geological feature that has likely been instrumental in generating biodiversity
      by providing opportunities for both vicariant and ecological speciation. However,
      the role of these mountains in the diversification of insects, which dominate
      biodiversity, has been poorly explored using phylogenetic methods. Here we study
      the role of the Andes in the evolution of a diverse Neotropical insect group, the
      clearwing butterflies. We used dated species-level phylogenies to investigate the
      time course of speciation and to infer ancestral elevation ranges for two diverse
      genera. We show that both genera likely originated at middle elevations in the
      Andes in the Middle Miocene, contrasting with most published results in
      vertebrates that point to a lowland origin. Although we detected a signature of
      vicariance caused by the uplift of the Andes at the Miocene-Pliocene boundary,
      most sister species were parapatric without any obvious vicariant barrier.
      Combined with an overall decelerating speciation rate, these results suggest an
      important role for ecological speciation and adaptive radiation, rather than
      simple vicariance.

PMID- 19386036
TI  - A retrospective study on the microbiology in patients with oral complaints and
      oral mucosal lesions.
AB  - OBJECTIVE: The aim of this study was to microbiologically analyze oral mucosal
      samples collected during 2 years from patients with oral mucosal complaints.
      MATERIALS AND METHODS: Mucosal scraping samples were taken from 297 patients and
      semiquantified by culture for detection of opportunistic microorganisms e.g.
      Staphylococcus aureus, enterococci, aerobic Gram-negative bacilli (AGNB) and
      yeasts. Antibiotic susceptibility test was performed. RESULTS: Altogether 297
      patients were sampled (mean age 56.8 +/- 20.7). Among the 110 patients with known
      medical condition, 48 were systemically immunocompromised, 35 had systemic
      diseases, and 27 had only local oral complaints. Opportunists in moderate growth
      or more were present commonly in all three groups and most frequent in the
      immunocompromised patients (66.7%). Candida species were the most frequent
      opportunist (68.8%), however, their level was low and combinations with bacterial
      opportunists were common (39.6%). All bacterial opportunists tested were
      antibiotic multiresistant. Follow-up samples were collected in 23 cases out of
      which seven showed still presence of opportunists in heavy growth despite
      repeated treatment with ciprofloxacin. CONCLUSIONS: This study showed a frequent
      presence of bacterial and fungal opportunists in patients with oral mucosal
      complaints, which were most common in immunocompromised individuals, however,
      also frequent in patients with local oral complaints only. Systematic evaluation
      of different treatment strategies is needed.

PMID- 19386039
TI  - Discovering genetic polymorphisms in next-generation sequencing data.
AB  - The ongoing revolution in DNA sequencing technology now enables the reading of
      thousands of millions of nucleotide bases in a single instrument run. However,
      this data quantity is often compromised by poor confidence in the read quality.
      The identification of genetic polymorphisms from this data is therefore
      problematic and, combined with the vast quantity of data, poses a major
      bioinformatics challenge. However, once these difficulties have been addressed,
      next-generation sequencing will offer a means to identify and characterize the
      wealth of genetic polymorphisms underlying the vast phenotypic variation in
      biological systems. We describe the recent advances in next-generation sequencing
      technology, together with preliminary approaches that can be applied for single
      nucleotide polymorphism discovery in plant species.

PMID- 19386040
TI  - A genome-wide analysis of single nucleotide polymorphism diversity in the world's
      major cereal crops.
AB  - Over 3.5 million expressed sequence tags from the major cereal taxa were used to
      electronically mine over 176,000 putative single nucleotide polymorphisms (SNPs).
      The density, distribution and degree of linkage between these SNPs were compared
      among the different taxa. The frequency of sequence polymorphism was lowest in
      diploid taxa (rice, barley and sorghum), intermediate in tetraploid maize and
      highest in allohexaploid wheat and octoploid sugarcane. SNPs were further
      categorized as either intravarietal (differences between gene family members and
      homoeologues) or varietal (differences between two varieties), and as either co
      segregating or non-co-segregating with neighbouring polymorphisms. Varietal co
      segregating SNPs represent the best candidates for molecular markers as they show
      variation between varieties and have a high probability of being validated, as
      sequencing errors are unlikely to co-segregate with one another. This elite class
      of SNPs was most abundant in barley and least abundant in wheat and rice. Despite
      the large number of observed sequence polymorphisms in allohexaploid wheat, only
      a fraction of those available are likely to make good molecular markers. In
      addition, we found that rice SNPs up to 10 kb apart were in linkage
      disequilibrium (LD), but that high levels of LD attributable to population
      structure confounded the tracking of LD over greater distances.

PMID- 19386041
TI  - Single nucleotide polymorphism discovery in barley using autoSNPdb.
AB  - Molecular markers are used to provide the link between genotype and phenotype,
      for the production of molecular genetic maps and to assess genetic diversity
      within and between related species. Single nucleotide polymorphisms (SNPs) are
      the most abundant molecular genetic marker. SNPs can be identified in silico, but
      care must be taken to ensure that the identified SNPs reflect true genetic
      variation and are not a result of errors associated with DNA sequencing. The SNP
      detection method autoSNP has been developed to identify SNPs from sequence data
      for any species. Confidence in the predicted SNPs is based on sequence
      redundancy, and haplotype co-segregation scores are calculated for a further
      independent measure of confidence. We have extended the autoSNP method to produce
      autoSNPdb, which integrates SNP and gene annotation information with a graphical
      viewer. We have applied this software to public barley expressed sequences, and
      the resulting database is available over the Internet. SNPs can be viewed and
      searched by sequence, functional annotation or predicted synteny with a reference
      genome, in this case rice. The correlation between SNPs and barley cultivar,
      expressed tissue type and development stage has been collated for ease of
      exploration. An average of one SNP per 240 bp was identified, with SNPs more
      prevalent in the 5' regions and simple sequence repeat (SSR) flanking sequences.
      Overall, autoSNPdb can provide a wealth of genetic polymorphism information for
      any species for which sequence data are available.

PMID- 19386042
TI  - Targeted single nucleotide polymorphism (SNP) discovery in a highly polyploid
      plant species using 454 sequencing.
AB  - Discovering single nucleotide polymorphisms (SNPs) in specific genes in a
      heterozygous polyploid plant species, such as sugarcane, is challenging because
      of the presence of a large number of homologues. To discover SNPs for mapping
      genes of interest, 454 sequencing of 307 polymerase chain reaction (PCR)
      amplicons (> 59 kb of sequence) was undertaken. One region of a four-gasket
      sequencing run, on a 454 Genome Sequencer FLX, was used for pooled PCR products
      amplified from each parent of a quantitative trait locus (QTL) mapping population
      (IJ76-514 x Q165). The sequencing yielded 96,755 (IJ76-514) and 86,241 (Q165)
      sequences with perfect matches to a PCR primer used in amplification, with an
      average sequence depth of approximately 300 and an average read length of 220
      bases. Further analysis was carried out on amplicons whose sequences clustered
      into a single contig using an identity of 80% with the program cap3. In the more
      polymorphic sugarcane parent (Q165), 94% of amplicons (227/242) had evidence of a
      reliable SNP--an average of one every 35 bases. Significantly fewer SNPs were
      found in the pure Saccharum officinarum parent--with one SNP every 58 bases and
      SNPs in 86% (213/247) of amplicons. Using automatic SNP detection, 1632 SNPs were
      detected in Q165 sequences and 1013 in IJ76-514. From 225 candidate SNP sites
      tested, 209 (93%) were validated as polymorphic using the Sequenom MassARRAY
      system. Amplicon re-sequencing using the 454 system enables cost-effective SNP
      discovery that can be targeted to genes of interest and is able to perform in the
      highly challenging area of polyploid genomes.

PMID- 19386043
TI  - Functional brain-electrical correlates of negative priming in the flanker task:
      evidence for episodic retrieval.
AB  - Negative priming (NP) refers to inefficient responding when previous distractors
      become targets. NP may reflect persisting inhibition of former distractors and/or
      retrieval of task-inappropriate information from the primes. In an event-related
      potential (ERP) study of the flanker task, NP was accompanied by reduced
      positivity in the P300 time range. The early portion of this effect was shared
      with a target-repetition condition and hence may indicate retrieval processes
      cued by repeated stimuli. A subsequent N400-like component was specific for NP
      and may reflect processing of the retrieved task-inappropriate information. In
      addition, NP effects on the lateralized readiness potential (LRP) matched
      predictions of the episodic-retrieval view. NP effects on P300, N400, and
      response-locked LRP were stronger in participants with above-median behavioral
      NP, confirming the significance of these ERP effects for NP. Overall, findings
      support episodic-retrieval explanations of NP.

PMID- 19386044
TI  - Impaired response selection in schizophrenia: evidence from the P3 wave and the
      lateralized readiness potential.
AB  - Reaction times (RTs) are substantially prolonged in schizophrenia patients, but
      the latency of the P3 component is not. This suggests that the RT slowing arises
      from impairments in a late stage of processing. To test this hypothesis, 20
      schizophrenia patients and 20 control subjects were tested in a visual oddball
      paradigm that was modified to allow measurement of the lateralized readiness
      potential (LRP), an index of stimulus-response translation processes. Difference
      waves were used to isolate the LRP and the P3 wave. Patients and control subjects
      exhibited virtually identical P3 difference waves, whereas the LRP difference
      wave was reduced in amplitude and delayed in latency in the patients. These
      results indicate that, at least in simple tasks, the delayed RTs observed in
      schizophrenia are primarily a consequence of impairments in the response
      selection and preparation processes that follow perception and categorization.

PMID- 19386045
TI  - A simple classification tool for single-trial analysis of ERP components.
AB  - Event-related potentials (ERPs) were recorded by measuring a dense sensor EEG
      from eight healthy volunteers in a visual oddball experiment. Single trials were
      analyzed with an extremely simple high-dimensional version of discriminant
      analysis. The question was how many of the target trials contribute to the
      average P3, and to test whether other components in the ERP are sensitive to
      discriminate between target and non-target trials. One common classification rule
      for all participants expressing the P3 component correctly classified 88% of the
      ERPs of all subjects in response to a target or non-target trial. For four of the
      eight participants, there were strong differences in an early ERP component over
      the occipital recording sites. Their individual classification rules, obtained
      from the training data in the time interval up to 200 ms, correctly classified
      85% of the trials of the test data.

PMID- 19386046
TI  - Genetic and environmental influences on frontal EEG asymmetry and alpha power in
      9-10-year-old twins.
AB  - Modest genetic influences on frontal EEG asymmetry have been found in adults, but
      little is known about its genetic origins in children. Resting frontal asymmetry
      and alpha power were examined in 951 9-10-year-old twins. Results showed that in
      both males and females: (1) a modest but significant amount of variance in
      frontal asymmetry was accounted for by genetic factors (11-28%) with the
      remainder accounted for by non-shared environmental influences, and (2) alpha
      power were highly heritable, with 71-85% of the variance accounted for by genetic
      factors. Results suggest that the genetic architecture of frontal asymmetry and
      alpha power in late childhood are similar to that in adulthood and that the high
      non-shared environmental influences on frontal asymmetry may reflect
      environmentally influenced individual differences in the maturation of frontal
      cortex as well as state-dependent influences on specific measurements.

PMID- 19386047
TI  - When beef primes reef more than leaf: orthographic information affects
      phonological priming in spoken word recognition.
AB  - This study was designed to investigate orthographic effects on spoken word
      recognition by combining the priming paradigm with a measure of event-related
      brain potentials (ERPs). Primes and targets either shared both orthography and
      phonology of the rhyme (beef-reef) or they shared rhyme phonology only (leaf
      reef). The two "related" conditions were compared against an "unrelated"
      condition (sick-reef). The results revealed a significant orthographic priming
      effect that was present on the early part of the N400 and that occurred as early
      as the phonological priming effect itself. Importantly, phonological and
      orthographic priming effects had different topographic distributions: The
      phonological priming effect was localized over centro-posterior regions, whereas
      the orthographic priming effect was more anterior. These results support a theory
      according to which orthographic information is coactivated online in spoken word
      recognition.

PMID- 19386048
TI  - Autonomic reactions to mutilation pictures: positive affect facilitates safety
      signal processing.
AB  - For survival, humans are continuously vigilant for signs of danger. Equally
      important, but less studied, is our ability to detect and respond to safety cues.
      The trait of positive affect may be a key component determining human variability
      in safety detection. Here we investigate autonomic and self-report reactivity to
      pictures of mutilated bodies, after reading a text about the art of mimicking
      injuries in the movies. Participants that scored high in positive affect trait
      showed attenuated autonomic reactions to the mutilation pictures. Thus, high
      positive affect facilitated engagement in safety cues and modulated reflexive
      reactions of the brain's defense system.

PMID- 19386050
TI  - The application of subliminal priming in lie detection: scenario for
      identification of members of a terrorist ring.
AB  - We studied a lie detection protocol immune to countermeasures. The 4 stimulus
      conditions were (1 and 2) supraliminal acquaintance name primed by subliminal
      acquaintance name (A-A) versus subliminal nonacquaintance name (N-A) and (3 and
      4) supraliminal nonacquaintance name primed by subliminal acquaintance name (A-N)
      versus subliminal nonacquaintance name (N-N). In Experiment 1 and replication,
      principal components analysis-derived event-related potential components revealed
      significant differences between dishonestly answered supraliminal acquaintance
      conditions with differing primes (A-A vs. N-A). In Experiment 2 subjects were
      required to lie in A-N and N-N conditions, in contrast to Experiment 1, in which
      subjects lied in A-A and N-A conditions. No significant effects were found. In
      Experiment 3, the lying task was removed and no significant differences were
      found. We conclude that subliminal primes modulate ERPs in conditions with
      supraliminal acquaintance name when the task involves lying.

PMID- 19386049
TI  - The impact of menstrual cycle phase on cardiac autonomic regulation.
AB  - This study investigated menstrual cycle phase differences in heart rate (HR) and
      RR interval variability (RRV) in 49 healthy, premenopausal, eumenorrheic women
      (age 30.2+/-6.2 years). HR and RRV were computed from ambulatory 24-h
      electrocardiogram, collected for up to 6 days, with at least 1 day each during
      early to midfollicular and midluteal menstrual phases. Phase effects on HR and
      RRV were assessed using linear mixed effects models with a random intercept to
      account for the correlation of observations within each subject as well as
      intrasubject variation. During follicular phase monitoring, women had
      significantly lower average HR (-2.33 bpm), and higher standard deviation, the
      root mean squared successive difference, and high frequency (0.04-0.15 Hz) and
      low frequency (0.15-0.40 Hz) RRV than during the luteal phase. These results
      provide strong support for the influence of menstrual phase on cardiac autonomic
      regulation in premenopausal women.

PMID- 19386051
TI  - Fear potentiated startle at short intervals following conditioned stimulus onset
      during delay but not trace conditioning.
AB  - The latency of conditioned fear after delay and trace conditioning was
      investigated. Some argue that delay conditioning is not dependent on awareness.
      In contrast, trace conditioning, where there is a gap between the conditioned
      stimulus (CS) and the unconditioned stimulus (US), is assumed to be dependent on
      awareness. In the present study, a tone CS signaled a noise US presented 1000 ms
      after CS onset in the delay conditioning group. In the trace conditioning group,
      a 200-ms tone CS was followed by an 800-ms gap prior to US presentation. Fear
      potentiated startle should be seen at shorter intervals after delay conditioning
      compared to trace conditioning. Analyses showed increased startle at 30, 50, 100,
      and 150 ms after CS onset following delay conditioning compared to trace
      conditioning. This implies that fear-relevant stimuli elicit physiological
      reactions before extended processing of the stimuli occur, following delay, but
      not trace conditioning.

PMID- 19386052
TI  - Protective effect of interval exercise on psychophysiological stress reactivity
      in children.
AB  - Two studies determined whether interval exercise reduces children's stress
      reactivity. For Experiment 1 children completed interval exercise (n=14) or
      watched TV (n=14) for 25 min. After 20 min rest children completed a speech task.
      Speech-induced diastolic blood pressure (DBP) reactivity was dampened in the
      exercise group (p<.05). For Experiment 2 children (n=22) completed interval
      exercise-speech and TV-speech conditions on separate days. Physical activity was
      assessed by accelerometry and aerobic fitness estimated by submaximal exercise.
      DBP, systolic BP, and heart rate (HR) reactivity to the speech stressor were
      dampened (p<.05) after exercise compared to TV watching. Fitness was positively
      associated with HR reactivity. Interval exercise that mimics usual patterns of
      physically active play dampens cardiovascular reactivity to interpersonal stress.

PMID- 19386053
TI  - Unmasking emotion: exposure duration and emotional engagement.
AB  - Effects of exposure duration on emotional reactivity were investigated in two
      experiments that parametrically varied the duration of exposure to affective
      pictures from 25-6000 ms in the presence or absence of a visual mask. Evaluative,
      facial, autonomic, and cortical responses were measured. Results demonstrated
      that, in the absence of a visual mask (Experiment 1), emotional content modulated
      evaluative ratings, cortical, autonomic, and facial changes even with very brief
      exposures, and there was little evidence that emotional engagement increased with
      longer exposure. When information persistence was reduced by a visual mask
      (Experiment 2), differences as a function of hedonic content were absent for all
      measures when exposure duration was 25 ms but statistically reliable when
      exposure duration was 80 ms. Between 25-80 ms, individual differences in
      discriminability were critical in observing affective reactions to masked
      pictures.

PMID- 19386054
TI  - Distraction of task-relevant information processing by irrelevant changes in
      auditory, visual, and bimodal stimulus features: a behavioral and event-related
      potential study.
AB  - Distractibility with auditory, visual, and bimodal stimulus changes was
      investigated using an audio-visual distraction paradigm. Participants were asked
      to discriminate between equiprobable short and long audio-visual stimuli.
      Infrequently, the auditory, the visual, or both parts of the stimuli changed.
      These rare deviations (deviants) were irrelevant for the actual task. The
      influence of the three types of deviant stimuli on the processing of task
      relevant information was assessed with behavioral and event-related potential
      (ERP) measures assuming that bimodal deviants would lead to an increase in
      distraction. Behavioral and ERP results did not support this assumption, as
      reaction time (RT) prolongation and components amplitudes did not differ
      significantly for auditory and bimodal deviants. It is suggested that a maximal
      threshold of distraction accounts for these results. In addition, the processing
      of bimodal deviations was assessed. Audio-visual interactions were found
      following modality-specific deviance detection suggesting that integration only
      occurs with involuntary attention switching to task-irrelevant changes.

PMID- 19386055
TI  - Publication ethics.

PMID- 19386056
TI  - Health problems and health behaviors of Korean preschoolers living with parents
      and under guardianship.
AB  - PURPOSE: A comparative analysis was conducted to identify and compare the health
      status and behaviors of preschoolers attending daycare centers in South Korea
      between children living with parents and those under guardianship. DESIGN: The
      study design was descriptive and correlational. SAMPLE: Data were collected from
      152 parents and 85 guardians of preschool children using a structured
      questionnaire. RESULTS: Of 237 children, 23.9-32.5% were overweight or obese,
      while 13.8-30.0% were underweight. Boys under guardianship were more likely to be
      obese. Hand-foot-mouth disease and atopic dermatitis were more prevalent among
      children living with parents, while those under guardianship were less likely to
      have dentistry visits, more likely to be absent from childcare due to pneumonia,
      and had significantly fewer health-related conversations with their guardians. In
      relation to health behaviors, the frequency of tooth-brushing and high-calcium
      food consumption was significantly lower among children under guardianship than
      among those living with parents. CONCLUSION: Compared with children living with
      parents, those under guardianship were exposed to unfavorable circumstances in
      terms of health management practices and health behaviors, which implies that the
      guardians were less interested in health care and dealt inappropriately with the
      health problems of their foster children.

PMID- 19386057
TI  - Workplace health promotion activities of Finnish occupational health nurses.
AB  - OBJECTIVE: This study describes workplace centered activities performed by
      occupational health professionals, as well as difficulties linked to workplace
      centered activities, cooperation with client workplaces, and participation both
      in risk assessment and in the development of working environment. DESIGN: The
      design is a cross-sectional prevalence study. SAMPLE: The questionnaires were
      sent to 250 occupational health professionals, of whom 176 (70%) returned the
      completed forms and of whom 99% were nurses. MEASUREMENTS: Their activities,
      difficulties, cooperation, and participation in risk assessment and development
      of safe and healthy working conditions. ANALYTIC STRATEGY: The data were analyzed
      by using frequencies, means, 1-way ANOVA, and the Kruskal-Wallis test. RESULTS:
      Workplace focused activity hours were mainly spent on risk assessment and
      counseling. One workplace visit took approximately 4 hr. The greatest
      difficulties were encountered with participation in development projects and in
      monitoring the effectiveness of improvement activities, especially in health care
      centers. Occupational health nurses cooperated with client enterprises and
      participated in risk assessment more often than the other occupational health
      professionals. Also workplace representatives participated actively in risk
      assessment. The most difficult modules were considered to be the risk assessment
      of chemicals, biological factors, and perceived stress, this being especially so
      in health care centers. CONCLUSIONS: It is essential that occupational health
      professionals visit more often in their client enterprises and improve their
      skills in preventing harms caused by chemical and biological factors, and
      perceived stress.

PMID- 19386058
TI  - Correlates of community health service utilization for menopausal symptoms among
      urban Japanese women.
AB  - OBJECTIVES: This study aims to identify the factors associated with community
      health service utilization for menopausal symptoms among Japanese women in urban
      areas by using Andersen's behavioral model of health service use. DESIGN: A cross
      sectional study was conducted. SAMPLE: The sample comprised 350 women aged 40-60
      years living in a community in Japan. MEASUREMENTS: The independent variables
      were predisposing (demographics, social status, and health beliefs), enabling
      (family and community resources), and need factors (perceived health status and
      the need for community health services). The dependent variable was community
      health service utilization. A logistic regression model was used. RESULTS: 8 of
      the women were categorized in "treatment required" by simplified menopausal index
      score, and 103 women said that they would use the services. Knowledge regarding
      the services, OR: 1.814 (1.084-3.036); the absence of a negative attitude toward
      menopausal syndromes, OR: 0.605 (0.367-0.998); and the presence of a positive
      attitude, OR: 2.203 (1.070-4.536); influenced community health service
      utilization. CONCLUSIONS: An appropriate attitude toward menopausal symptoms was
      observed to be more relevant to community health service utilization than the
      experience or acuity of the menopausal symptoms themselves. Therefore, community
      dwelling, middle-aged women should be provided with sufficient education
      regarding menopausal symptoms to encourage their utilization of community health
      services.

PMID- 19386059
TI  - The effects of a walking program on older Chinese American immigrants with
      hypertension: a pretest and posttest quasi-experimental design.
AB  - OBJECTIVE: Hypertension is known to have high rates among Chinese Americans.
      Identifying culturally specific interventions to reduce sedentary behavior may be
      effective in reducing hypertension. This study examines the effects of an 8-week
      walking program with and without cultural modification. DESIGN: The study used a
      2-group, pretest and posttest, quasi-experimental design. SAMPLE: A total sample
      of 128 Chinese American immigrants with hypertension were assigned to walking
      groups. RESULTS: The results showed that the walking program had no significant
      effects upon participant blood pressure or walking endurance. The results also
      revealed that individuals in the maintenance stage walked longer than those in
      the preparation stage. A comparison of demographic data showed that subjects with
      a lower level of education walked more minutes per week, which contributed to
      lower systolic blood pressures among this group as compared with those with a
      higher level of education. CONCLUSIONS: These results suggest that this walking
      protocol, when translated into Chinese and when accompanied by a weekly telephone
      reminder and other interactions with a Chinese-speaking nurse, is appropriate to
      use without additional cultural modification. Future research should examine
      other components of Chinese culture or should apply this protocol for a longer
      period of time.

PMID- 19386060
TI  - Assessment of depressive symptoms and cognitive impairment in elders from rural
      areas of the Brazilian State of Rio Grande do Sul.
AB  - OBJECTIVE: The main objective of this study was to examine the relationships
      among demographic characteristics, depressive symptoms, and cognitive impairment
      in oldest-old elders from rural areas of the Brazilian State of Rio Grande do
      Sul. DESIGN: A cross-sectional, descriptive correlational design was used to
      conduct the study. SAMPLE: 137 Brazilian elders age 80 years or over.
      MEASUREMENTS: A target population data form, a county data form, a demographic
      questionnaire, the Mini-Mental State Examination, and the Depressive Cognition
      Scale were used to collect the data. RESULTS: A significant difference was found
      between males and females in regard to cognitive impairment. In addition,
      educational level and depressive symptoms were correlated with cognitive
      impairment. Depressive symptoms were a weak but significant predictor of
      cognitive impairment after controlling for the effect of age, gender, and
      educational level of the oldest-old elders. CONCLUSIONS: The findings need to be
      interpreted cautiously since the sample scored above the cutoff points for
      cognitive impairment, and had low scores on depressive symptoms. Despite several
      limitations, findings from this study can be a foundation for further studies,
      and well-designed correlational or experimental approaches, are warranted.

PMID- 19386061
TI  - Effects of a cognition-oriented breast self-examination intervention for Korean
      women and their spouses.
AB  - OBJECTIVE: This study evaluated the effectiveness of a cognition-oriented breast
      self-examination (BSE) intervention program that is based on the Transtheoretical
      Model and reflects individual characteristics according to BSE stage among Korean
      women and their spouses. DESIGN: A time-series nonequivalent control group design
      was used. SAMPLE AND MEASUREMENT: Twenty-four couples in each of 2 groups
      completed a preintervention test and were evaluated 1, 3, and 6 months later for
      their knowledge of breast cancer and BSE, spousal encouragement for BSE,
      perceived confidence in BSE methods, change in BSE stage, and perceived benefits
      and barriers to BSE. The intervention involved husbands as well as women, and
      consisted of lectures on breast cancer and BSE, demonstrations and practice with
      models while being videotaped, and feedback. RESULTS: There were significant
      differences between the control and experimental groups for all variables. Change
      of BSE stage in experimental group showed significantly advancement over time.
      CONCLUSIONS: This intervention program was effective in promoting regular BSE
      practice and in enhancing confidence in BSE. The intervention also raised
      awareness among husbands of the importance of breast health for their wives.
      Educational interventions for breast cancer prevention should be specified to an
      individual's stage of BSE.

PMID- 19386062
TI  - Social support and cervical and breast cancer screening in Argentinean women from
      a rural population.
AB  - OBJECTIVE: To examine whether emotional social support influences the use of 3
      cancer screening tests in females. DESIGN: Cross-sectional study. SAMPLE: Data
      were collected via a household survey of a random sample of 200 Argentinean
      women. MEASUREMENTS: The questionnaire included self-reported data about the
      cancer screening tests (Papanicolaou [Pap] test for cervical cancer, breast self
      examination, and clinical examination for breast cancer), and socioeconomic
      background information. Social support was measured by the Duke-UNC-11
      questionnaire. ANALYSIS: Logistic models were used to investigate the association
      between social support and cancer screening tests. RESULTS: Emotional social
      support was associated with having participated in Pap screening within 3 years
      before this study, but a link between social support and self or clinical breast
      examination was not supported. CONCLUSION: Emotional social support may play a
      role in early cervical cancer detection among Argentinean females, specifically
      by encouraging performance of the Pap test. The educational practices
      accomplished by nurses should include actions that involve the family and
      community; therefore, emphasizing the importance of social ties on health and
      promoting interactions between target women and existent social groups in the
      community.

PMID- 19386063
TI  - Do specialist community public health nurses assess risk factors for depression,
      suicide, and self-harm among South Asian mothers living in London?
AB  - Evidence indicates that suicide rates are higher in South Asian women in the
      United Kingdom compared with other ethnic groups, suggesting increased
      vulnerability to attempted suicide and mental distress in these women. Specialist
      Community Public Health Nurses (SCPHNs, including health visitors) are in an
      ideal position to assess such risk. The objectives are to determine whether
      SCPHNs assess known risk factors for depression, self-harm, and suicide during
      initial contact with South Asian mothers in London; the extent to which these
      risk factors are documented in the nursing records; and whether their assessments
      of South Asian women differ from those of other ethnic groups. Structured content
      analysis of semistructured interviews with 8 SCPHNs and analysis of 60 matched
      pairs of SCPHN records were carried out in an inner London community. The results
      revealed that SCPHNs assessed general risk factors for postnatal depression and
      some culture-specific factors when assessing South Asian mothers. Documentation
      of risk factors was under-represented in the SCPHN records and there was a
      significant difference between the documented risk factors for South Asian women
      and women from other ethnic groups. While SCPHNs understood some aspects of South
      Asian culture, service improvements must be made to ensure better care provision.

PMID- 19386064
TI  - The retirement of a public health nurse leader.
AB  - Elizabeth Gordon Fox was a distinguished member of the profession and an
      influential advocate for visiting nurse services at the time of her retirement.
      The dinner guests who came to honor her 20 years as director of the New Haven,
      Connecticut Visiting Nurse Association included luminaries in public health
      including Thomas Parran, Ira V. Hiscock, Ruth Hubbard, and Anna Fillmore. Dr. C.
      E. A. Winslow, an eminent leader in public health, and Annie Warburton Goodrich,
      the retired dean of the Yale School of Nursing were also present. The occasion
      was marked by an address by Thomas Parran, former U. S. Surgeon General, who
      focused attention on nursing leadership in public health. Speeches by both Parran
      and Fox addressed the challenges faced at mid-century-challenges of public
      accountability, of a widespread nursing shortage, and of the need to distribute
      knowledge and services with both efficiency and compassion. Dr. Parran's talk and
      an excerpt from Fox's comments that evening were published in Public Health
      Nursing in December 1949. Selected passages from each of their speeches recall
      for contemporary readers the concerns of the era and the hopes of those who had
      dedicated their professional careers to improvement of the health of the public.

PMID- 19386066
TI  - Airline policy for passengers requiring supplemental in-flight oxygen.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the current
      Australian/New Zealand airline policy on supplemental in-flight oxygen for
      passengers with lung disease. METHODS: Fifty-four commercial airlines servicing
      international routes were surveyed. Information was gathered from airline call
      centres and web sites. The survey documented individual airline policy on in
      flight oxygen delivery, approval schemes, equipment and cost. RESULTS: Of the 54
      airlines contacted, 43 (81%) were able to support passengers requiring in-flight
      oxygen. The majority (88%) of airlines provided a cylinder for passengers to use.
      Airline policy for calculating the cost of in-flight oxygen differed considerably
      between carriers. Six (14%) airlines supplied oxygen to passengers free of
      charge; however, three of these airlines charged for an extra seat. Fifteen
      airlines (35%) charged on the basis of oxygen supplied, that is, per cylinder.
      Fourteen airlines (33%) had a flat rate charge per sector. CONCLUSIONS: This
      study confirmed that most airlines can accommodate passengers requiring
      supplemental oxygen. However, the findings highlight inconsistencies in airline
      policies and substantial cost differences for supplemental in-flight oxygen. We
      advocate an industry standardization of policy and cost of in-flight oxygen.

PMID- 19386067
TI  - Predicting the response to air travel in passengers with non-obstructive lung
      disease: are the current guidelines appropriate?
AB  - BACKGROUND AND OBJECTIVE: Air travel guidelines recommend using baseline arterial
      oxygen levels and the hypoxic challenge test (HCT) to predict in-flight
      hypoxaemia and the requirement for in-flight oxygen in patients with lung
      disease. The purpose of the present study was to (i) quantify the hypoxaemic
      response to air travel and (ii) identify baseline correlate(s) to predict this
      response in passengers with non-obstructed lung disease. METHODS: Fourteen
      passengers (seven women) with chronic non-obstructed lung disease volunteered for
      this study. The study involved three phases: (i) respiratory function testing;
      (ii) in-flight measures (SpO(2), cabin pressure and dyspnoea); and (iii) a HCT.
      The in-flight hypoxaemic response was compared with the baseline arterial oxygen
      level, respiratory function and the HCT. RESULTS: All subjects flew without
      oxygen and no adverse events were recorded in-flight. Mean cabin pressure was 593
      +/- 16 mm Hg. Pre-flight SpO(2) was 95 +/- 3% and significantly decreased to 85
      +/- 9% in-flight, with further significant falls in subjects who walked during
      the flight (nadir SpO(2) 78 +/- 11%). The pre-flight SpO(2) showed the strongest
      correlation with in-flight SpO(2) (r = 0.91, P < 0.001). The HCT SpO(2) was
      moderately correlated to the in-flight SpO(2) (r = 0.58, P < 0.05). Spirometry,
      D(L,CO) and TLC measurements did not correlate with in-flight SpO(2). CONCLUSION:
      Significant in-flight desaturation can be expected in passengers with non
      obstructive lung disease. Respiratory function did not predict in-flight
      desaturation. We found a good relationship between pre-flight SpO(2) and in
      flight SpO(2) which supports the role of pre-flight oximetry for predicting in
      flight hypoxaemia in passengers with non-obstructed lung disease.

PMID- 19386068
TI  - Correlation of C-reactive protein with disease severity in CT diagnosed
      emphysema.
AB  - BACKGROUND AND OBJECTIVE: Recent studies suggest that CRP levels are related to
      airflow obstruction. However, limited data exist on the relevance of CRP levels
      in individuals with or without emphysema. The aim of this study was to assess the
      relationship between the extent of emphysema, COPD severity and serum CRP levels.
      METHODS: Lung function tests and high-sensitivity CRP were examined in 651 males
      with stable disease who underwent CT screening for lung cancer. CRP levels were
      examined cross-sectionally in individuals with various degrees of emphysema and
      in those without emphysema. RESULTS: Emphysema was detected in 179 (34.7%) of 516
      current smokers. Airflow obstruction was observed in 47 (28.8%) of 163 smokers
      with mild emphysema, in eight (57.1%) of 14 smokers with moderate emphysema, and
      in two of two individuals with severe emphysema. CRP levels were not higher in
      individuals with mild or moderate emphysema compared with individuals without
      emphysema. Among 98 individuals with airflow obstruction (19.0% of the 516
      current smokers), there was a modest correlation between CRP levels and FEV(1)%.
      CONCLUSIONS: The severity of COPD varied in individuals with similar degrees of
      emphysema. CRP levels were not significantly higher in individuals with mild or
      moderate emphysema compared with individuals without emphysema but CRP levels
      were modestly correlated with FEV(1)% among individuals with airflow obstruction.

PMID- 19386069
TI  - Clinical outcomes in sarcoidosis after cessation of infliximab treatment.
AB  - BACKGROUND AND OBJECTIVE: Infliximab appears to be efficacious for the treatment
      of recalcitrant forms of sarcoidosis. However, there are minimal data concerning
      the course of sarcoidosis once infliximab is discontinued. METHODS: Clinical
      outcomes in patients who had received infliximab and had discontinued it for at
      least 2 months were analysed retrospectively. The severity of involvement of the
      index organ from the time of discontinuation of infliximab was compared with that
      at the end of the follow-up period. RESULTS: Fourteen patients with sarcoidosis
      who had been treated with infliximab and had discontinued this therapy were
      identified. Before discontinuation of infliximab, 9 of the 14 patients (64%)
      responded to infliximab treatment and only one (7%) deteriorated. Patients who
      discontinued infliximab were followed for a mean of 12 months. At the end of the
      follow-up period, 12 of the 14 patients (86%) had deteriorated as compared with
      their status at the time of discontinuation of infliximab and two (14%) had
      remained stable. Kaplan-Meier analysis of time to clinical deterioration showed
      that half the patients deteriorated within 3 months of discontinuing infliximab.
      Patients who had discontinued infliximab appeared to be more likely to have their
      dose of prednisone increased. CONCLUSION: Patients with recalcitrant sarcoidosis
      who receive infliximab appear likely to deteriorate after discontinuation of this
      medication.

PMID- 19386070
TI  - Attenuation of lipopolysaccharide-induced acute lung injury by treatment with IL
      10.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to characterize the changes
      in neutrophils and cytokines in BAL fluid following acute lung injury (ALI), and
      to determine the protective effect of post-injury treatment with IL-10. METHODS:
      A rat model of ALI was established by evenly spraying LPS (16 mg/kg) into the
      lungs followed by observation for 48 h. Histological changes and the kinetics of
      neutrophil infiltration were evaluated in the injured lungs. The cytokines (TNF
      alpha, IL-6, IL-10 and interferon-gamma) and macrophage-inflammatory protein (MIP
      2) were measured in BAL fluid by ELISA. The activation of BAL fluid neutrophils
      was investigated after treatment with IL-10 in vitro. The protective effect on
      histology and MIP-2 levels of intra-tracheal instillation of IL-10 12 and 16 h
      after LPS treatment was studied in vivo. RESULTS: Intra-tracheal instillation of
      LPS caused significant lung injury and the activation of neutrophils. The levels
      of TNF-alpha and IL-6 in BAL fluid peaked at 8 and 16 h after LPS instillation
      respectively. IL-10 levels reached a maximum at 16-24 h, at the beginning of
      resolution of tissue injury. IL-10 inhibited the activation of neutrophils in
      vitro and MIP-2 induction in vivo. IL-10 had a protective effect if it was
      administered 12 but not 16 h after LPS. CONCLUSIONS: Neutrophils appeared to play
      an important role in ALI. Time-dependent treatment with IL-10 after intra
      tracheal instillation of LPS was effective in protecting rats from ALI, probably
      by suppressing pulmonary infiltration with activated neutrophils.

PMID- 19386071
TI  - Non-invasive ventilation improves peripheral oxygen saturation and reduces
      fatigability of quadriceps in patients with COPD.
AB  - BACKGROUND AND OBJECTIVE: Non-invasive ventilation (NIV) might improve peripheral
      muscle function and exercise capacity in severely disabled patients. This study
      evaluated the physiological impact of NIV on isokinetic concentric strength and
      endurance of lower limb muscles in patients with severe COPD. METHODS: This
      clinical trial tested COPD patients (n = 24) and healthy subjects (n = 18).
      Subjects underwent isokinetic dynamometry tests while given either bi-level
      positive airway pressure ventilation (BV) or sham ventilation (SV), in a
      randomized order with 30 min of rest prior to each intervention. The inspiratory
      level of BV was set up to 14 cm H(2)O and expiratory pressure up to 6 cm H(2)O.
      Peripheral oxygen saturation (SpO(2)), heart rate (HR), systolic (SBP) and
      diastolic blood pressure (DBP) at the peak of exercise were measured for each
      intervention. RESULTS: Compared with controls, COPD patients had lower values of
      SpO(2) and HR (P < 0.01) during both BV and SV and lower values of DBP (P < 0.01)
      during BV. BV improved SpO(2) (P < 0.01), and reduced SBP in both COPD (P < 0.01)
      and control groups (P < 0.05) and reduced DBP in COPD patients (P < 0.01). BV
      also reduced the fatigue index in COPD patients when compared with SV (P =
      0.003). Variation (BV-SV) of total work at the peak of the test was higher in the
      control group than in the COPD group (P < 0.05). CONCLUSIONS: BV improved SpO(2)
      and reduced the fatigability of the quadriceps muscle in patients with severe
      COPD. These results support the need for further evaluation of BV as adjunct
      during high-intensity strength exercise training in these patients.

PMID- 19386072
TI  - Neuromuscular disease in the dialysis patient: an update for the nephrologist.
AB  - Neuromuscular disease is an extremely common complication of end-stage kidney
      disease (ESKD), manifesting in almost all dialysis patients, and leading to
      weakness, reduced exercise capacity, and disability. Recent studies have
      suggested that hyperkalemia may underlie the development of neuropathy. As such,
      maintenance of serum K(+) within normal limits between periods of dialysis in
      ESKD patients manifesting early neuropathic symptoms may reduce neuropathy
      development and progression. For patients with more severe neuropathic syndromes,
      increased dialysis frequency or a switch to high-flux dialysis may prevent
      further deterioration, while ultimately, renal transplantation is required to
      improve and restore nerve function. Exercise training programs are beneficial for
      ESKD patients with muscle weakness due to neuropathy or myopathy, and are capable
      of improving exercise tolerance and quality of life. Specific treatments have
      recently been evaluated for symptoms of autonomic neuropathy, including
      sildenafil for impotence and midodrine for intra-dialytic hypotension, and have
      been shown to be effective and well tolerated. Other important management
      strategies for neuropathy include attention to foot care to prevent callus and
      ulceration, vitamin supplementation, and erythropoietin. Treatment with membrane
      stabilizing agents, such as amitryptiline and gabapentin, are highly effective in
      patients with painful neuropathy.

PMID- 19386073
TI  - Aminoglycosides in hemodialysis patients: is the current practice of post
      dialysis dosing appropriate?
AB  - Aminoglycosides have been widely used in end-stage renal failure patients for the
      treatment of infections caused by gram-negative bacilli and Staphylococcus
      aureus. Traditionally, these agents are administered post dialysis to avoid
      premature dialytic clearance, although no studies have been performed to confirm
      that this dosing strategy represents the optimal treatment regimen. In recent
      years, a more complete understanding of the pharmacokinetics-pharmacodynamics of
      aminoglycosides has led to a global change in clinical practice from multiple to
      once-daily dosing in patients with normal renal function with the aim of
      providing intermittent pulses to maximize the peak concentration relative to
      overall drug exposure. These same considerations strongly support administration
      of aminoglycosides before, rather than after, hemodialysis. This study will
      review the key pharmacokinetic/pharmacodynamic considerations in aminoglycoside
      dosing, the relationship between serum aminoglycoside concentrations and
      efficacy/toxicity, the influence of renal function and hemodialysis on
      aminoglycoside pharmacokinetics/pharmacodynamics, and the mounting population
      pharmacokinetic and clinical study evidence supporting a paradigm shift in
      aminoglycoside dosing from post dialysis to predialysis.

PMID- 19386074
TI  - Laparoscopy in the early diagnosis and management of sclerosing encapsulating
      peritonitis.
AB  - Sclerosing encapsulating peritonitis (SEP) is a rare and dreaded complication
      that can occur in patients undergoing peritoneal dialysis (PD). Although risk
      factors have been identified, the diagnosis is difficult and is usually made late
      in the disease after extensive fibrosis of the peritoneal membrane has occurred,
      at which point therapy is often fruitless. The high mortality rate of SEP is due
      to complications resulting from recurrent bowel obstruction, malnutrition, and
      sepsis. We report three patients with signs and symptoms suggestive of SEP all of
      whom had normal abdominal CT scans. Nevertheless, each patient underwent
      diagnostic laparoscopy, which confirmed the clinical suspicion of SEP. In each
      case, the diagnosis was made before extensive peritoneal fibrosis had occurred
      allowing therapeutic intervention at an early stage. All three patients
      subsequently became asymptomatic and thrived. This clinical improvement was
      supported by the lack of progression to overt peritoneal fibrosis on repeat
      laparoscopy. We conclude that a high index of suspicion in conjunction with a low
      threshold for diagnostic laparoscopy may be an effective strategy to establish an
      early diagnosis and treatment regimen for SEP. Additionally, repeat laparoscopy
      can be used to guide the length of therapy. These interventions may ultimately
      improve the long-term morbidity and mortality of SEP.

PMID- 19386075
TI  - The estimated number of patients with hepatocellular carcinoma selected for liver
      transplantation using expanded selection criteria.
AB  - Recently, several groups have introduced expanded criteria for selection of
      patients with hepatocellular carcinoma (HCC) prior to transplant, but the exact
      number of potential newly recruited patients remains unclear. This registry-based
      study assessed 270 patients diagnosed with HCC. The potential number of
      transplant candidates was based on age (< or =65 years), absence of metastases
      and macro-vascular invasion, and on 12 previously published, expanded selection
      criteria. A wide range of increase in the number of transplant candidates was
      observed (12-63% when compared with the number of such candidates who would have
      been selected solely based on the Milan criteria). The most conservative criteria
      were Seoul (Kwon, 2007; increase of 12%), Valencia (Silva, 2008; 16%), total
      tumor volume/alpha-fetoprotein (Toso, 2009; 20%) and UCSF (Yao, 2007; 20%). This
      data will assist Centers and policy agencies in predicting the need for resources
      linked to an expansion of criteria.

PMID- 19386076
TI  - Interventions to improve medication-adherence after transplantation: a systematic
      review.
AB  - Reports of interventions to improve adherence to medical regimens in solid organ
      transplant recipients are scarce. A systematic review identified 12 intervention
      studies. These studies focused on renal, heart, and liver transplant recipients.
      Five reports used randomized controlled trial (RCT) designs. Sample sizes varied
      between 18 and 110 subjects. The interventions are difficult to evaluate and
      categorize because of brief descriptions of intervention details. Of the 12
      studies identified in this review, only five studies found a statistically
      significant improvement in at least one medication-adherence outcome with the
      intervention. In general, most included a combination of patient-focused
      cognitive/educational, counseling/behavioral, and psychologic/affective
      dimensions. Eight studies intervened at the healthcare provider, healthcare
      setting or healthcare system level, but showed a limited improvement in
      adherence. No single intervention proved to be superior at increasing medication
      adherence in organ transplantation, but a combination of interventions in a team
      approach for the chronic disease management of organ transplant patients may be
      effective in a long-term perspective. In conclusion, finding the most effective
      combination of interventions to enhance adherence is vital. Utilizing an RCT
      design and adhering to the CONSORT guidelines can lead to higher quality studies
      and possibly more effective intervention studies to enhance medication-adherence.

PMID- 19386077
TI  - Congestion of the donor remnant right liver after extended left lobe donation.
AB  - The clinical importance of congestion of the remnant right lobe has not yet been
      fully elucidated in donors who donate their left lobe with the middle hepatic
      vein. The impact of congestion on clinical course and liver regeneration in 52
      donor remnant livers were evaluated. The donors were divided into three groups
      according to the degree of the congestion: the mild [congestion ratio (CR) <
      10%], moderate (CR ranged from 10% to 25%) and severe congestion groups (CR >
      25%). The regeneration ratio of the graft at postoperative day 7 (7 POD) was 22.0
      +/- 14.3% and inversely correlated with the CR in the remnant right lobe (P =
      0.003). Aspartate aminotransferase and alanine aminotransferase at 7 POD were
      significantly higher in the severe CR group in comparison to the mild CR group (P
      = 0.003 and 0.019, respectively), but those of the three groups were comparable
      at 30 POD. The hospital stays were significantly longer in the severe CR group (P
      = 0.010). In conclusion, the congestion of the donors' remnant right liver can
      lead the transient liver dysfunction and poor regeneration. Therefore, the
      conversion of the graft from the left to right lobe might be appropriate
      according to the degree of the congestion.

PMID- 19386078
TI  - Role of NK and NKT cells in solid organ transplantation.
AB  - In the context of solid organ transplantation, the exact interactions between the
      innate and adaptive alloimmune response have not yet been fully explored. In this
      transplant setting, natural killer (NK) cells have emerged as a particular focus
      of interest because of their ability to distinguish allogeneic major
      histocompatibility complex (MHC) antigens and their potent cytolytic activity.
      Based on this observation and its potential clinical relevance, NK cells have
      recently been shown to participate in the immune response in both acute and
      chronic rejection of solid organ allografts. Numerous experimental and clinical
      studies demonstrate that NK cells determine transplant survival by rejecting an
      allograft not directly but indirectly by providing bystander effects. In
      addition, NK cells are influenced by immunosuppressive therapies such as
      calcineurin inhibitors or steroids. As NK and natural killer T (NKT) cells have
      also been shown to play a profound role in allograft tolerance induction, this
      review summarizes the major findings to highlight the functional role of these
      lymphocyte subsets, which may constitute an underestimated mechanism affecting
      graft outcome in solid organ transplantation.

PMID- 19386079
TI  - Impact of immunosuppression on the incidence of early subclinical renal allograft
      rejection: implications for protocol biopsy policy.
AB  - In order to determine the impact of immunosuppression (IS) on the incidence of
      early subclinical rejection (SCR), we studied two groups of patients receiving
      different immunosuppressive regimens. Patients received cyclosporin (CsA),
      azathioprine and prednisolone (group 1; n = 304) or IS according to immunological
      risk (group 2; n = 150). The highest-risk patients received basiliximab
      induction, tacrolimus, mycophenolate mofetil (MMF) and prednisolone; medium-risk
      patients CsA, MMF and prednisolone; low-risk CsA, azathioprine and prednisolone.
      Protocol biopsies were performed in all patients, irrespective of graft function,
      on days 7 and 28 post-transplantation. Only patients with good stable function at
      the time of biopsy were included for assessment of SCR. Group 2 patients showed
      significant reductions in total rejection frequency (32.6% vs. 57.2%, P =
      <0.0001) and SCR frequency in day 7 protocol biopsies (2% vs. 13%, P = <0.05). In
      group 2 patients, all SCRs, but not borderline changes, were treated. Untreated
      borderline changes did not have an adverse impact on graft function at 1 year
      post-transplantation. New immunosuppressive regimens may reduce subclinical in
      addition to clinical rejection-frequency, suggesting that the relative benefit of
      early protocol biopsies in detecting SCR is also reduced.

PMID- 19386080
TI  - Mycotic pseudoaneurysm as aortic complication after heart transplantation.

PMID- 19386081
TI  - Effect of conversion from mycophenolate mofetil to enteric-coated mycophenolate
      sodium on maximum tolerated dose and gastrointestinal symptoms following kidney
      transplantation.
AB  - Despite the potential tolerability advantage of enteric-coated mycophenolate
      sodium (EC-MPS), no prospective, randomized trial has evaluated whether
      conversion from mycophenolate mofetil (MMF) to EC-MPS permits mycophenolic acid
      dose to be increased or gastrointestinal side-effects to be ameliorated. In a
      randomized, multicenter, open-label trial, kidney transplant recipients
      experiencing gastrointestinal side-effects either remained on MMF or switched to
      an equimolar dose of EC-MPS, adjusted 2 weeks subsequently to target the highest
      tolerated dose up to 1440 mg/day (EC-MPS) or 2000 mg/day (MMF). Patients were
      followed up to 12 weeks postrandomization. One hundred and thirty-four patients
      were randomized. The primary efficacy endpoint, the proportion of patients
      receiving a higher mycophenolic acid (MPA) dose at week 12 than at randomization,
      was significantly greater in the EC-MPS arm (32/68, 47.1%) than the MMF arm
      (10/61, 16.4%; P < 0.001). At the final visit, 50.0% (34/68) of EC-MPS patients
      were receiving the maximum recommended dose versus 26.2% (16/61) of MMF patients
      (P = 0.007). Kidney transplant patients receiving reduced-dose MMF because of
      gastrointestinal side-effects can tolerate a significant increase in MPA dose
      after conversion to EC-MPS. Patient-reported gastrointestinal outcomes with
      higher doses of EC-MPS remained at least as good as in MMF-treated controls.

PMID- 19386082
TI  - Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in
      renal transplantation.
AB  - m-TOR inhibitors (e.g. sirolimus) are well-tolerated immunosuppressants used in
      renal transplantation for prophylaxis of organ rejection, and are associated with
      long-term graft survival. Early use of sirolimus is often advocated by
      clinicians, but this may be associated with a number of side-effects including
      impaired wound-healing, lymphoceles and delayed graft function. As transplant
      clinicians with experience in the use of sirolimus, we believe such side-effects
      can be limited by tailored clinical management. We present recommendations based
      on published literature and our clinical experience. Furthermore, guidance is
      provided on sirolimus use during surgery, both at transplantation and for
      subsequent operations.

PMID- 19386083
TI  - Differential effects of Staphylococcal enterotoxin B-mediated immune activation
      on intestinal defensins.
AB  - In the small intestine members of both the alpha-defensin (DEFA5 and DEFA6) and
      beta-defensin (DEFB1 and DEFB2) family contribute to the anti-microbial barrier
      against infection. The aim of this study was to determine whether Staphylococcal
      enterotoxin B (SEB)-mediated immune activation and proinflammatory cytokines play
      a role in the regulation of intestinal defensin expression. Defensin mRNA and
      peptide secretion was studied after ex vivo tissue culture of duodenal biopsies
      over 24 h. Immune (T cell and macrophage) activation was induced by SEB, and in
      separate experiments exogenous proinflammatory cytokines were added individually.
      Defensin mRNA levels were quantified by reverse transcription-polymerase chain
      reaction, and peptide release into culture supernatants was quantified by immuno
      dot blot or enzyme-linked immunosorbent assay. Increasing concentrations of SEB
      down-regulated DEFA5, DEFA6 and DEFB1 mRNA in a dose-dependent manner but
      increased DEFB2 simultaneously. The down-regulation of alpha-defensins was
      reversed by dexamethasone. DEFA5 and DEFB2 peptide secretion levels were altered
      in parallel with mRNA. Interferon-gamma and interleukin (IL)-1beta exhibited a
      dose-dependent down-regulation of alpha-defensin mRNA, IL-6 significantly down
      regulated only DEFA6; in contrast, tumour necrosis factor-alpha and IL-4 had no
      significant effect. Immune cell activation and proinflammatory cytokines down
      regulated the constitutively expressed DEFA5, DEFA6 and DEFB1 defensins, and up
      regulated DEFB2 in intact human intestinal tissue explants in short-term culture.
      The effect of local immune activation on innate defence may explain the reduced
      alpha-defensin expression noted in inflammatory T cell-mediated enteropathies.

PMID- 19386084
TI  - Targeting eEF1A by a Legionella pneumophila effector leads to inhibition of
      protein synthesis and induction of host stress response.
AB  - The Legionella pneumophila Dot/Icm type IV secretion system is essential for the
      biogenesis of a phagosome that supports bacterial multiplication, most likely via
      the functions of its protein substrates. Recent studies indicate that fundamental
      cellular processes, such as vesicle trafficking, stress response, autophagy and
      cell death, are modulated by these effectors. However, how each translocated
      protein contributes to the modulation of these pathways is largely unknown. In a
      screen to search substrates of the Dot/Icm transporter that can cause host cell
      death, we identified a gene whose product is lethal to yeast and mammalian cells.
      We demonstrate that this protein, called SidI, is a substrate of the Dot/Icm type
      IV protein transporter that targets the host protein translation process. Our
      results indicate that SidI specifically interacts with eEF1A and eEF1Bgamma, two
      components of the eukaryotic protein translation elongation machinery and such
      interactions leads to inhibition of host protein synthesis. Furthermore, we have
      isolated two SidI substitution mutants that retain the target binding activity
      but have lost toxicity to eukaryotic cells, suggesting potential biochemical
      effect of SidI on eEF1A and eEF1Bgamma. We also show that infection by L.
      pneumophila leads to eEF1A-mediated activation of the heat shock regulatory
      protein HSF1 in a virulence-dependent manner and deletion of sidI affects such
      activation. Moreover, similar response occurred in cells transiently transfected
      to express SidI. Thus, inhibition of host protein synthesis by specific effectors
      contributes to the induction of stress response in L. pneumophila-infected cells.

PMID- 19386085
TI  - Evaluation of surveillance case definition in the diagnosis of leptospirosis,
      using the Microscopic Agglutination Test: a validation study.
AB  - BACKGROUND: Leptospirosis is endemic in both urban and rural areas of Sri Lanka
      and there had been many out breaks in the recent past. This study was aimed at
      validating the leptospirosis surveillance case definition, using the Microscopic
      Agglutination Test (MAT). METHODS: The study population consisted of patients
      with undiagnosed acute febrile illness who were admitted to the medical wards of
      the Teaching Hospital Kandy, from 1st July 2007 to 31st July 2008. The subjects
      were screened to diagnose leptospirosis according to the leptospirosis case
      definition. MAT was performed on blood samples taken from each patient on the 7th
      day of fever. Leptospirosis case definition was evaluated in regard to
      sensitivity, specificity and predictive values, using a MAT titre >or= 1:800 for
      confirming leptospirosis. RESULTS: A total of 123 patients were initially
      recruited of which 73 had clinical features compatible with the surveillance case
      definition. Out of the 73 only 57 had a positive MAT result (true positives)
      leaving 16 as false positives. Out of the 50 who didn't have clinical features
      compatible with the case definition 45 had a negative MAT as well (true
      negatives), therefore 5 were false negatives. Total number of MAT positives was
      62 out of 123. According to these results the test sensitivity was 91.94%,
      specificity 73.77%, positive predictive value and negative predictive values were
      78.08% and 90% respectively. Diagnostic accuracy of the test was 82.93%.
      CONCLUSION: This study confirms that the surveillance case definition has a very
      high sensitivity and negative predictive value with an average specificity in
      diagnosing leptospirosis, based on a MAT titre of >or= 1: 800.

PMID- 19386086
TI  - Immunomodulatory parasites and toll-like receptor-mediated tumour necrosis factor
      alpha responsiveness in wild mammals.
AB  - BACKGROUND: Immunological analyses of wild populations can increase our
      understanding of how vertebrate immune systems respond to 'natural' levels of
      exposure to diverse infections. A major recent advance in immunology has been the
      recognition of the central role of phylogenetically conserved toll-like receptors
      in triggering innate immunity and the subsequent recruitment of adaptive response
      programmes. We studied the cross-sectional associations between individual levels
      of systemic toll-like receptor-mediated tumour necrosis factor alpha
      responsiveness and macro- and microparasite infections in a natural wood mouse
      (Apodemus sylvaticus) population. RESULTS: Amongst a diverse group of
      macroparasites, only levels of the nematode Heligmosomoides polygyrus and the
      louse Polyplax serrata were correlated (negatively) with innate immune
      responsiveness (measured by splenocyte tumour necrosis factor alpha responses to
      a panel of toll-like receptor agonists). Polyplax serrata infection explained a
      strikingly high proportion of the total variation in innate responses.
      Contrastingly, faecal oocyst count in microparasitic Eimeria spp. was positively
      associated with innate immune responsiveness, most significantly for the
      endosomal receptors TLR7 and TLR9. CONCLUSION: Analogy with relevant laboratory
      models suggests the underlying causality for the observed patterns may be
      parasite-driven immunomodulatory effects on the host. A subset of
      immunomodulatory parasite species could thus have a key role in structuring other
      infections in natural vertebrate populations by affecting the 'upstream' innate
      mediators, like toll-like receptors, that are important in initiating immunity.
      Furthermore, the magnitude of the present result suggests that populations free
      from immunosuppressive parasites may exist at 'unnaturally' elevated levels of
      innate immune activation, perhaps leading to an increased risk of
      immunopathology.

PMID- 19386087
TI  - Rifampin pharmacokinetics in children, with and without human immunodeficiency
      virus infection, hospitalized for the management of severe forms of tuberculosis.
AB  - BACKGROUND: Rifampin is a key drug in antituberculosis chemotherapy because it
      rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse
      and thus enables 6-month short-course chemotherapy. Little is known about the
      pharmacokinetics of rifampin in children. The objective of this study was to
      evaluate the pharmacokinetics of rifampin in children with tuberculosis, both
      human immunodeficiency virus type-1-infected and human immunodeficiency virus
      uninfected. METHODS: Fifty-four children, 21 human immunodeficiency virus
      infected and 33 human immunodeficiency virus-uninfected, mean ages 3.73 and 4.05
      years (P = 0.68), respectively, admitted to a tuberculosis hospital in Cape Town,
      South Africa with severe forms of tuberculosis were studied approximately 1 month
      and 4 months after commencing antituberculosis treatment. Blood specimens for
      analysis were drawn in the morning, 45 minutes, 1.5, 3.0, 4.0 and 6.0 hours after
      dosing. Rifampin concentrations were determined by liquid chromatography tandem
      mass spectrometry. For two sample comparisons of means, the Welch version of the
      t-test was used; associations between variables were examined by Pearson
      correlation and by multiple linear regression. RESULTS: The children received a
      mean rifampin dosage of 9.61 mg/kg (6.47 to 15.58) body weight at 1 month and
      9.63 mg/kg (4.63 to 17.8) at 4 months after commencing treatment administered as
      part of a fixed-dose formulation designed for paediatric use. The mean rifampin
      area under the curve 0 to 6 hours after dosing was 14.9 and 18.1 microg/hour/ml
      (P = 0.25) 1 month after starting treatment in human immunodeficiency virus
      infected and human immunodeficiency virus-uninfected children, respectively, and
      16.52 and 17.94 microg/hour/ml (P = 0.59) after 4 months of treatment. The mean
      calculated 2-hour rifampin concentrations in these human immunodeficiency virus
      infected and human immunodeficiency virus-uninfected children were 3.9 and 4.8
      microg/ml (P = 0.20) at 1 month after the start of treatment and 4.0 and 4.6
      microg/ml (P = 0.33) after 4 months of treatment. These values are considerably
      less than the suggested lower limit for 2-hour rifampin concentrations in adults
      of 8.0 microg/ml and even 4 microg/ml CONCLUSION: Both human immunodeficiency
      virus-infected and human immunodeficiency virus-uninfected children with
      tuberculosis have very low rifampin serum concentrations after receiving standard
      rifampin dosages similar to those used in adults. Pharmacokinetic studies of
      higher dosages of rifampin are urgently needed in children to assist in placing
      the dosage of rifampin used in childhood on a more scientific foundation.

PMID- 19386088
TI  - The effect of varying analytical methods on estimates of anti-malarial clinical
      efficacy.
AB  - BACKGROUND: Analytical approaches for the interpretation of anti-malarial
      clinical trials vary considerably. The aim of this study was to quantify the
      magnitude of the differences between efficacy estimates derived from these
      approaches and identify the factors underlying these differences. METHODS: Data
      from studies conducted in Africa and Thailand were compiled and the risk
      estimates of treatment failure, adjusted and unadjusted by genotyping, were
      derived by three methods (intention to treat (ITT), modified intention to treat
      (mITT) and per protocol (PP)) and then compared. RESULTS: 29 clinical trials (15
      from Africa and 14 from Thailand) with a total of 65 treatment arms (38 from
      Africa and 27 from Thailand) were included in the analysis. Of the 15,409
      patients enrolled, 2,637 (17.1%) had incomplete follow up for the unadjusted
      analysis and 4,489 (33.4%) for the adjusted analysis. Estimates of treatment
      failure were consistently higher when derived from the ITT or PP analyses
      compared to the mITT approach. In the unadjusted analyses the median difference
      between the ITT and mITT estimates was greater in Thai studies (11.4% [range 2.1
      31.8]) compared to African Studies (1.8% [range 0-11.7]). In the adjusted
      analyses the median difference between PP and mITT estimates was 1.7%, but ranged
      from 0 to 30.9%. The discrepancy between estimates was correlated significantly
      with the proportion of patients with incomplete follow-up; p < 0.0001. The
      proportion of studies with a major difference (> 5%) between adjusted PP and mITT
      was 28% (16/57), with the risk difference greater in African (37% 14/38) compared
      to Thai studies (11% 2/19). In the African studies, a major difference in the
      adjusted estimates was significantly more likely in studies in high transmission
      sites (62% 8/13) compared to studies in moderate transmission sites (24% 6/25); p
      = 0.035. CONCLUSION: Estimates of anti-malarial clinical efficacy vary
      significantly depending on the analytical methodology from which they are
      derived. In order to monitor temporal and spatial trends in anti-malarial
      efficacy, standardized analytical tools need to be applied in a transparent and
      systematic manner.

PMID- 19386089
TI  - Brain metastasis development and poor survival associated with carcinoembryonic
      antigen (CEA) level in advanced non-small cell lung cancer: a prospective
      analysis.
AB  - BACKGROUND: Central nervous system is a common site of metastasis in NSCLC and
      confers worse prognosis and quality of life. The aim of this prospective study
      was to evaluate the prognostic significance of clinical-pathological factors
      (CPF), serum CEA levels, and EGFR and HER2 tissue-expression in brain metastasis
      (BM) and overall survival (OS) in patients with advanced NSCLC. METHODS: In a
      prospective manner, we studied 293 patients with NSCLC in IIIB-IV clinical stage.
      They received standard chemotherapy. CEA was measured prior to treatment; EGFR
      and HER2 were evaluated by immunohistochemistry. BM development was confirmed by
      MRI in symptomatic patients. RESULTS: BM developed in 27, and 32% of patients at
      1 and 2 years of diagnosis with adenocarcinoma (RR 5.2; 95% CI, 1.002-29; p =
      0.05) and CEA > or = 40 ng/mL (RR 11.4; 95% CI, 1.7-74; p < 0.01) as independent
      associated factors. EGFR and HER2 were not statistically significant. Masculine
      gender (RR 1.4; 95% CI, 1.002-1.9; p = 0.048), poor performance status (RR 1.8;
      95% CI, 1.5-2.3; p = 0.002), advanced clinical stage (RR 1.44; 95% CI, 1.02-2; p
      = 0.04), CEA > or = 40 ng/mL (RR 1.5; 95% CI, 1.09-2.2; p = 0.014) and EGFR
      expression (RR 1.6; 95% CI, 1.4-1.9; p = 0.012) were independent associated
      factors to worse OS. CONCLUSION: High CEA serum level is a risk factor for BM
      development and is associated with poor prognosis in patients with advanced
      NSCLC. Surface expression of CEA in tumor cells could be the physiopathological
      mechanism for invasion to CNS.

PMID- 19386090
TI  - High abundances of neurotrophin 3 in atopic dermatitis mast cell.
AB  - BACKGROUND: Neurotrophin 3 (NT-3) is a member of the neurotrophin family, a group
      of related proteins that are known to regulate neuro-immune interactions in
      allergic diseases. Their cellular sources and role in the recruitment of mast
      cell precursors in atopic dermatitis have not been characterized in detail so
      far. OBJECTIVE: Characterize NT-3 on a transcriptional and translational level in
      individuals with atopic dermatitis with special focus on mast cells. METHODS: To
      meet this objective NT-3 levels in the serum of AD patients were measured, the
      effect of NT-3 on keratinocytes was evaluated and the gene expression and
      regulation assessed using ELISA, immunohistochemistry and RNA quantification.
      RESULTS: Systemic levels of NT-3 were found to be higher in individuals with AD
      as compared to healthy controls. A distinct genetic expression was found in the
      various cells of the skin. In lesional mast cells of individuals with atopic
      dermatitis an increased amount of NT-3 was apparent. Functional in vitro
      experiments demonstrated that NT-3 stimulation led to a suppression of IL-8
      secretion by HaCat cells. CONCLUSION: These findings could imply a role for NT-3
      in the pathogenesis of allergic skin diseases.

PMID- 19386091
TI  - Recursive regularization for inferring gene networks from time-course gene
      expression profiles.
AB  - BACKGROUND: Inferring gene networks from time-course microarray experiments with
      vector autoregressive (VAR) model is the process of identifying functional
      associations between genes through multivariate time series. This problem can be
      cast as a variable selection problem in Statistics. One of the promising methods
      for variable selection is the elastic net proposed by Zou and Hastie (2005).
      However, VAR modeling with the elastic net succeeds in increasing the number of
      true positives while it also results in increasing the number of false positives.
      RESULTS: By incorporating relative importance of the VAR coefficients into the
      elastic net, we propose a new class of regularization, called recursive elastic
      net, to increase the capability of the elastic net and estimate gene networks
      based on the VAR model. The recursive elastic net can reduce the number of false
      positives gradually by updating the importance. Numerical simulations and
      comparisons demonstrate that the proposed method succeeds in reducing the number
      of false positives drastically while keeping the high number of true positives in
      the network inference and achieves two or more times higher true discovery rate
      (the proportion of true positives among the selected edges) than the competing
      methods even when the number of time points is small. We also compared our method
      with various reverse-engineering algorithms on experimental data of MCF-7 breast
      cancer cells stimulated with two ErbB ligands, EGF and HRG. CONCLUSION: The
      recursive elastic net is a powerful tool for inferring gene networks from time
      course gene expression profiles.

PMID- 19386092
TI  - The components of the Daphnia pulex immune system as revealed by complete genome
      sequencing.
AB  - BACKGROUND: Branchiopod crustaceans in the genus Daphnia are key model organisms
      for investigating interactions between genes and the environment. One major theme
      of research on Daphnia species has been the evolution of resistance to pathogens
      and parasites, but lack of knowledge of the Daphnia immune system has limited the
      study of immune responses. Here we provide a survey of the immune-related genome
      of D. pulex, derived from the newly completed genome sequence. Genes likely to be
      involved in innate immune responses were identified by comparison to homologues
      from other arthropods. For each candidate, the gene model was refined, and we
      conducted an analysis of sequence divergence from homologues from other taxa.
      RESULTS AND CONCLUSION: We found that some immune pathways, in particular the
      TOLL pathway, are fairly well conserved between insects and Daphnia, while other
      elements, in particular antimicrobial peptides, could not be recovered from the
      genome sequence. We also found considerable variation in gene family copy number
      when comparing Daphnia to insects and present phylogenetic analyses to shed light
      on the evolution of a range of conserved immune gene families.

PMID- 19386093
TI  - Number of teeth and myocardial infarction and stroke among elderly never smokers.
AB  - BACKGROUND: In most previous studies the association between number of teeth and
      cardiovascular diseases has been found to be stronger among younger age groups
      than in older age groups, which indicates that age may modify the association
      between number of teeth and cardiovascular diseases. We investigated the
      association between tooth loss and atherosclerotic vascular diseases such as
      myocardial infarction and stroke in a homogeneous elderly population. The study
      population was comprised of a subpopulation of 392 community-living elderly
      people who participated in the population-based Kuopio 75+ study. The data were
      collected through an interview, a structured clinical health examination and from
      patient records. The main outcome measures were a history of diagnosed myocardial
      infarction and diagnosed ischemic stroke. Prevalence proportion ratios (PPR) were
      estimated using generalised linear models. RESULTS: Edentate subjects had a
      weakly, statistically non-significantly increased likelihood of a history of
      myocardial infarction and ischemic stroke compared with dentate subjects. Those
      with a large number of teeth had a slightly, but not statistically significantly
      increased likelihood of a history of myocardial infarction and ischemic stroke
      compared with those with a small number of teeth. CONCLUSION: These data did not
      show evidence that total or partial tooth loss would be associated with
      atherosclerotic vascular diseases such as myocardial infarction and ischemic
      stroke among an elderly population aged 75 years or older.

PMID- 19386094
TI  - Transcriptomic and metabolic responses of Staphylococcus aureus exposed to supra
      physiological temperatures.
AB  - BACKGROUND: Previous evaluation by different molecular and physiological assays
      of Staphylococcus aureus (S. aureus) responses to heat shock exposure yielded a
      still fragmentary view of the mechanisms determining bacterial survival or death
      at supra-physiological temperatures. This study analyzed diverse facets of S.
      aureus heat-shock adjustment by recording global transcriptomic and metabolic
      responses of bacterial cultures shifted for 10 min from 37 degrees C to a sub
      lethal (43 degrees C) or eventually lethal (48 degrees C) temperature. A relevant
      metabolic model of the combined action of specific stress response mechanisms
      with more general, energy-regulating metabolic pathways in heat-shocked S. aureus
      is presented. RESULTS: While S. aureus cultures shifted to 43 degrees C or left
      at 37 degrees C showed marginal differences in growth and survival rates,
      bacterial cultures exposed to 48 degrees C showed a rapid growth arrest followed
      by a subsequent decline in viable counts. The most substantial heat shock-induced
      changes at both 43 degrees C and 48 degrees C occurred in transcript levels of
      HrcA- and CtsR-regulated genes, encoding classical chaperones DnaK and GroESL,
      and some Hsp100/Clp ATPases components, respectively. Other metabolic pathways up
      regulated by S. aureus exposure at 48 degrees C included genes encoding several
      enzymes coping with oxidative stress, and DNA damage, or/and impaired osmotic
      balance. Some major components of the pentose phosphate cycle and gluconeogenesis
      were also up-regulated, which reflected depletion of free glucose by bacterial
      cultures grown in Mueller-Hinton broth prior to heat shock. In contrast, most
      purine- and pyrimidine-synthesis pathway components and amino acyl-tRNA
      synthetases were down-regulated at 48 degrees C, as well as arginine deiminase
      and major fermentative pathway components, such as alcohol, lactate and formate
      dehydrogenases. Despite the heat-induced, increased requirements for ATP
      dependent macromolecular repair mechanisms combined with declining energy
      sources, intracellular ATP levels remained remarkably constant during heat shock.
      CONCLUSION: The sequential loss of replication and viability at 48 degrees C
      cannot be explained by significant reductions in intracellular ATP levels, but
      may reflect ATP rerouting for macromolecular repair mechanisms and cell survival.
      Our metabolic model also suggests that heat-stressed S. aureus should down
      regulate the production of potential, DNA-damaging reactive oxygen species that
      might result from electron transport-generated ATP, involving excessive levels of
      free heavy metals, in particular iron.

PMID- 19386095
TI  - Expression of iron-related genes in human brain and brain tumors.
AB  - BACKGROUND: Defective iron homeostasis may be involved in the development of some
      diseases within the central nervous system. Although the expression of genes
      involved in normal iron balance has been intensively studied in other tissues,
      little is known about their expression in the brain. We investigated the mRNA
      levels of hepcidin (HAMP), HFE, neogenin (NEO1), transferrin receptor 1 (TFRC),
      transferrin receptor 2 (TFR2), and hemojuvelin (HFE2) in normal human brain,
      brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain
      tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2
      oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines.
      RESULTS: Except for hemojuvelin, all genes studied had detectable levels of mRNA.
      In most tumor types, the pattern of gene expression was diverse. Notable findings
      include high expression of transferrin receptor 1 in the hippocampus and medulla
      oblongata compared to other brain regions, low expression of HFE in normal brain
      with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in
      astrocytoma cell lines despite expression in normal brain and tumor specimens.
      CONCLUSION: These results indicate that several iron-related genes are expressed
      in normal brain, and that their expression may be dysregulated in brain tumors.

PMID- 19386096
TI  - Capecitabine plus Irinotecan (XELIRI regimen) compared to 5-FU/LV plus Irinotecan
      (FOLFIRI regimen) as neoadjuvant treatment for patients with unresectable liver
      only metastases of metastatic colorectal cancer: a randomised prospective phase
      II trial.
AB  - BACKGROUND: Phase II studies have shown that the combination of capecitabine and
      irinotecan (the XELIRI regimen) is active in metastatic colorectal cancer (MCRC).
      There are, however, no data about the use of the XELIRI regimen in the
      neoadjuvant treatment. METHODS: Patients with unresectable liver-only metastases
      of MCRC with < or = 75 years of age were randomised to either the XELIRI
      (irinotecan 250 mg/m(2) given on day one and capecitabine 1000 mg/m(2) twice
      daily from day 2-15, every 21 days) or the FOLFIRI arm (irinotecan 180 mg/m(2), 5
      FU 400 mg/m(2), LV 200 mg/m(2), 5-FU 2400 mg/m(2) (46-h infusion)--all given on
      day one, every 14 days). Primary end points were objective response rate (ORR)
      and rate of radical (R0) surgical resection. Secondary end points were
      progression-free survival (PFS), overall survival (OS) and safety. RESULTS:
      Altogether 87 patients were enrolled (41 pts in the XELIRI and 46 pts in the
      FOLFIRI arm). The median age was 63 years (63 years in the XELIRI and 62 years in
      the FOLFIRI arm) (p = 0.33). ORR was 49% in the XELIRI and 48% in the FOLFIRI arm
      (p = 0.76). The rate of radical R0 resection was 24% in both arms of patients. At
      the end of treatment, 37% of patients in the XELIRI and 26% of patients in the
      FOLFIRI arm were without evidence of the disease (CR+R0 resection) (p = 0.56).
      There were no statistical differences in grade 3 or 4 adverse events between both
      arms: diarrhoea 7% vs. 6%, neutropenia 5% vs. 13%, ischemic stroke 0 vs. 2%,
      acute coronary syndrome 2% vs. 4%, respectively. At the median follow up of 17
      (range 1-39) months, the median PFS was 10.3 months in the XELIRI and 9.3 months
      in the FOLFIRI arm (p = 0.78), the median OS was 30.7 months in the XELIRI arm
      and 16.6 months in the FOLFIRI arm (p = 0.16). CONCLUSION: The XELIRI regimen
      showed similar ORR as the FOLFIRI regimen in the neoadjuvant treatment of
      patients with MCRC. In addition, the XELIRI regimen showed similar PFS and OS
      with acceptable toxicity compared to the FOLFIRI regimen. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN19912492.

PMID- 19386097
TI  - Masked volume wise Principal Component Analysis of small adrenocortical tumours
      in dynamic [11C]-metomidate Positron Emission Tomography.
AB  - BACKGROUND: In previous clinical Positron Emission Tomography (PET) studies novel
      approaches for application of Principal Component Analysis (PCA) on dynamic PET
      images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was
      shown to be a feasible multivariate analysis technique, which, without modeling
      assumptions, could extract and separate organs and tissues with different kinetic
      behaviors into different principal components (MVW-PCs) and improve the image
      quality. METHODS: In this study, MVW-PCA was applied to 14 dynamic 11C-metomidate
      PET (MTO-PET) examinations of 7 patients with small adrenocortical tumours. MTO
      PET was performed before and 3 days after starting per oral cortisone treatment.
      The whole dataset, reconstructed by filtered back projection (FBP) 0-45 minutes
      after the tracer injection, was used to study the tracer pharmacokinetics.
      RESULTS: Early, intermediate and late pharmacokinetic phases could be isolated in
      this manner. The MVW-PC1 images correlated well to the conventionally summed
      image data (15-45 minutes) but the image noise in the former was considerably
      lower. PET measurements performed by defining "hot spot" regions of interest
      (ROIs) comprising 4 contiguous pixels with the highest radioactivity
      concentration showed a trend towards higher SUVs when the ROIs were outlined in
      the MVW-PC1 component than in the summed images. Time activity curves derived
      from "50% cut-off" ROIs based on an isocontour function whereby the pixels with
      SUVs between 50 to 100% of the highest radioactivity concentration were
      delineated, showed a significant decrease of the SUVs in normal adrenal glands
      and in adrenocortical adenomas after cortisone treatment. CONCLUSION: In addition
      to the clear decrease in image noise and the improved contrast between different
      structures with MVW-PCA, the results indicate that the definition of ROIs may be
      more accurate and precise in MVW-PC1 images than in conventional summed images.
      This might improve the precision of PET measurements, for instance in therapy
      monitoring as well as for delineation of the tumour in radiation therapy
      planning.

PMID- 19386098
TI  - Ranking differentially expressed genes from Affymetrix gene expression data:
      methods with reproducibility, sensitivity, and specificity.
AB  - BACKGROUND: To identify differentially expressed genes (DEGs) from microarray
      data, users of the Affymetrix GeneChip system need to select both a preprocessing
      algorithm to obtain expression-level measurements and a way of ranking genes to
      obtain the most plausible candidates. We recently recommended suitable
      combinations of a preprocessing algorithm and gene ranking method that can be
      used to identify DEGs with a higher level of sensitivity and specificity.
      However, in addition to these recommendations, researchers also want to know
      which combinations enhance reproducibility. RESULTS: We compared eight
      conventional methods for ranking genes: weighted average difference (WAD),
      average difference (AD), fold change (FC), rank products (RP), moderated t
      statistic (modT), significance analysis of microarrays (samT), shrinkage t
      statistic (shrinkT), and intensity-based moderated t statistic (ibmT) with six
      preprocessing algorithms (PLIER, VSN, FARMS, multi-mgMOS (mmgMOS), MBEI, and
      GCRMA). A total of 36 real experimental datasets was evaluated on the basis of
      the area under the receiver operating characteristic curve (AUC) as a measure for
      both sensitivity and specificity. We found that the RP method performed well for
      VSN-, FARMS-, MBEI-, and GCRMA-preprocessed data, and the WAD method performed
      well for mmgMOS-preprocessed data. Our analysis of the MicroArray Quality Control
      (MAQC) project's datasets showed that the FC-based gene ranking methods (WAD, AD,
      FC, and RP) had a higher level of reproducibility: The percentages of overlapping
      genes (POGs) across different sites for the FC-based methods were higher overall
      than those for the t-statistic-based methods (modT, samT, shrinkT, and ibmT). In
      particular, POG values for WAD were the highest overall among the FC-based
      methods irrespective of the choice of preprocessing algorithm. CONCLUSION: Our
      results demonstrate that to increase sensitivity, specificity, and
      reproducibility in microarray analyses, we need to select suitable combinations
      of preprocessing algorithms and gene ranking methods. We recommend the use of FC
      based methods, in particular RP or WAD.

PMID- 19386099
TI  - Multichromosomal median and halving problems under different genomic distances.
AB  - BACKGROUND: Genome median and genome halving are combinatorial optimization
      problems that aim at reconstructing ancestral genomes as well as the evolutionary
      events leading from the ancestor to extant species. Exploring complexity issues
      is a first step towards devising efficient algorithms. The complexity of the
      median problem for unichromosomal genomes (permutations) has been settled for
      both the breakpoint distance and the reversal distance. Although the
      multichromosomal case has often been assumed to be a simple generalization of the
      unichromosomal case, it is also a relaxation so that complexity in this context
      does not follow from existing results, and is open for all distances. RESULTS: We
      settle here the complexity of several genome median and halving problems,
      including a surprising polynomial result for the breakpoint median and guided
      halving problems in genomes with circular and linear chromosomes, showing that
      the multichromosomal problem is actually easier than the unichromosomal problem.
      Still other variants of these problems are NP-complete, including the DCJ double
      distance problem, previously mentioned as an open question. We list the remaining
      open problems. CONCLUSION: This theoretical study clears up a wide swathe of the
      algorithmical study of genome rearrangements with multiple multichromosomal
      genomes.

PMID- 19386100
TI  - Myxoid liposarcoma: a rare soft-tissue tumor with a misleading benign appearance.
AB  - BACKGROUND: Lipoma is by far the most common of all benign soft-tissue tumors
      which far outnumber malignant tumors. Soft-tissue sarcomas are malignant tumors
      and are usually named for the type of tissue in which they begin. Liposarcoma
      (LPS), which arises in the fatty tissue, is rather an uncommon soft-tissue tumor.
      Multiple histologic subtypes of liposarcoma are recognized, including myxoid
      liposarcoma, and correspond to tumors of very different prognosis. In two-third
      of the cases, this tumor occurs in the muscle while often demonstrating a
      misleading benign appearance as observed in the majority of soft-tissue sarcomas.
      CASE PRESENTATION: We report the case of a 50-year-old man operated on for a fat
      tumor of the thigh initially diagnosed as lipoma but revealing to be a myxoid
      liposarcoma after histopathological examination. The initial incomplete tumor
      excision required the need for a re-excision with adjuvant chemotherapy and
      complementary radiotherapy. CONCLUSION: When any suspicious soft-tissue tumor is
      diagnosed, the combined information gathered from accurate preoperative
      radiographic planning and X-rays or surgical biopsy is of tremendous value for
      establishing the most appropriate therapeutic program, highly adapted to the
      histopathological findings.

PMID- 19386101
TI  - Human embryonic stem cells hemangioblast express HLA-antigens.
AB  - BACKGROUND: It has been suggested that the initial differentiation of endothelial
      and hematopoietic cells during embryogenesis occurs from a common progenitor,
      called hemangioblast (hB). We hypothesized that these cells with dual
      hematopoietic/endothelial potential could be used in future regenerative
      medicine. METHODS: We used the two-step differentiation technology to generate
      bipotential blast cells from human embryonic stem cells (hES). This involved
      short differentiation in our in vitro EB system followed by differentiation in
      semisolid culture medium supplemented with mixture of cytokines. RESULTS: The
      occurrence of blast-colony-forming cells (BL-CFC) during EB differentiation (day
      0-6) was transient and peaked on day 3. The emergence of this event was
      associated with expression of mesoderm gene T, and inversely correlated with
      expression of endoderm gene FoxA2. Similarly, the highest BL-CFC number was
      associated with increase in expression of early hematopoietic/endothelial genes:
      CD34, CD31 and KDR. The derived colonies were composed of 30-50 blast cells on
      day 6 in culture. These cells had homogenous appearance in Wright-Giemsa stain,
      but to a different extent expressed markers of immature hematopoietic and
      endothelial cells (CD31, CD34, VE-cadherin, Flt-1) and mature differentiated
      cells (CD45, CD33, CD146). We found that some of them expressed fetal and
      embryonic globin genes. Interestingly, these cells expressed also HLA class I
      molecules, however at very low levels compared to endothelial and hematopoietic
      cells. The blast cells could be successfully differentiated to hematopoietic
      cells in a CFU assay. In these conditions, blast cells formed CFU-M colonies
      (63.4 +/- 0.8%) containing macrophages, BFU-E colonies (19.5 +/- 3.5%) containing
      nucleated red blood cells, and CFU-EM colonies (17.1 +/- 2.7%) composed of
      macrophages and nucleated erythrocytes. Cells of CFU-EM and BFU-E colonies
      expressed both epsilon - and gamma- globin genes, but not adult-type gamma
      globin. When in endothelial cell culture conditions, blast cells differentiated
      to endothelial cells which had the ability to take up Dil-Ac-LDL and to form
      complex vascular networks in Matrigel. CONCLUSION: 1) Hematoendothelial
      precursors exist transiently in early embryonic development and form single cell
      derived colonies; 2) their differentiation can be tracked by the use of chosen
      molecular markers; 3) blast colonies consist of cells having properties of
      endothelial and hematopoietic precursors, however the issue of their ability to
      maintain dual properties over time needs to be further explored; 4) blast cells
      can potentially be used in regenerative medicine due to their low expression of
      HLA molecules.

PMID- 19386102
TI  - Nitric oxide production by Biomphalaria glabrata haemocytes: effects of
      Schistosoma mansoni ESPs and regulation through the extracellular signal
      regulated kinase pathway.
AB  - BACKGROUND: Schistosoma mansoni uses Biomphalaria glabrata as an intermediate
      host during its complex life cycle. In the snail, the parasite initially
      transforms from a miracidium into a mother sporocyst and during this process
      excretory-secretory products (ESPs) are released. Nitric oxide (NO) and its
      reactive intermediates play an important role in host defence responses against
      pathogens. This study therefore aimed to determine the effects of S. mansoni ESPs
      on NO production in defence cells (haemocytes) from schistosome-susceptible and
      schistosome-resistant B. glabrata strains. As S. mansoni ESPs have previously
      been shown to inhibit extracellular signal-regulated kinase (ERK) phosphorylation
      (activation) in haemocytes from susceptible, but not resistant, B. glabrata the
      regulation of NO output by ERK in these cells was also investigated. RESULTS:
      Haemocytes from resistant snails challenged with S. mansoni ESPs (20 mug/ml) over
      5 h displayed an increase in NO production that was 3.3 times greater than that
      observed for unchallenged haemocytes; lower concentrations of ESPs (0.1-10
      mug/ml) did not significantly increase NO output. In contrast, haemocytes from
      susceptible snails showed no significant change in NO output following challenge
      with ESPs at any concentration used (0.1-20 mug/ml). Western blotting revealed
      that U0126 (1 muM or 10 muM) blocked the phosphorylation (activation) status of
      ERK in haemocytes from both snail strains. Inhibition of ERK signalling by U0126
      attenuated considerably intracellular NO production in haemocytes from both
      susceptible and resistant B. glabrata strains, identifying ERK as a key regulator
      of NO output in these cells. CONCLUSION: S. mansoni ESPs differentially influence
      intracellular NO levels in susceptible and resistant B. glabrata haemocytes,
      possibly through modulation of the ERK signalling pathway. Such effects might
      facilitate survival of S. mansoni in its intermediate host.

PMID- 19386103
TI  - Don't lose sight of the importance of the individual in effective falls
      prevention interventions.
AB  - Falls remain a major public health problem, despite strong growth in the research
      evidence of effective single and multifactorial interventions, particularly in
      the community setting. A number of aspects of falls prevention require individual
      tailoring, despite limitations being reported regarding some of these, including
      questions being raised regarding the role of falls risk screening and falls risk
      assessment. Being able to personalise an individual's specific risk and risk
      factors, increase their understanding of what interventions are likely to be
      effective, and exploring options of choice and preference, can all impact upon
      whether or not an individual undertakes and sustains participation in one or more
      recommendations, which will ultimately influence outcomes. On all of these
      fronts, the individual patient receiving appropriate and targeted interventions
      that are meaningful, feasible and that they are motivated to implement, remains
      central to effective translation of falls prevention research evidence into
      practice.

PMID- 19386104
TI  - Age-specific effects of estrogen receptors' polymorphisms on the bone traits in
      healthy fertile women: the BONTURNO study.
AB  - BACKGROUND: Skeletal characteristics such as height (Ht), bone mineral density
      (BMD) or bone turnover markers are strongly inherited. Common variants in the
      genes encoding for estrogen receptor alpha (ESR1) and beta (ESR2) are proposed as
      candidates for influencing bone phenotypes at the population level. METHODS: We
      studied 641 healthy premenopausal women aged 20-50 years (yrs) participating into
      the BONTURNO study. Exclusion criteria were irregular cyclic menses, low trauma
      fracture, metabolic bone or chronic diseases. Serum C-telopeptide of type I
      collagen (CTX), osteocalcin (OC), and N-terminal propeptide of type I procollagen
      (P1NP) were measured in all enrolled subjects, who underwent to lumbar spine
      (LS), total hip (TH) and femoral neck (FN) BMD evaluation by DXA. Five hundred
      seventy Caucasian women were genotyped for ESR1 rs2234693 and rs9340799 and ESR2
      rs4986938 polymorphisms. RESULTS: Although no genotype differences were found in
      body parameters, subjects with combined ESR1 CCGG plus ESR2 AA-AG genotype were
      taller than those with opposite genotype (P = 0.044). Moreover, ESR1 rs2234693
      genotypes correlated with family history of osteoporosis (FHO) and hip fracture
      (FHF) (P < 0.01), while ESR2 AA-AC genotypes were strongly associated with FHF
      (OR 2.387, 95% CI 1.432-3.977; P < 0.001).When clustered by age, 20-30 yrs old
      subjects, having at least one ESR1 rs2234693 C allele presented lower LS- (P =
      0.008) and TH-BMD (P = 0.047) than TT genotypes. In 41-50 yrs age, lower FN-BMD
      was associated with ESR2 AA (P = 0.0180) subjects than in those with the opposite
      genotype. ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms did not
      correlate with age-adjusted values of OC, CTX and P1NP. CONCLUSION: These
      findings support the presence of age-specific effects of ESR1 and ESR2
      polymorphisms on various skeletal traits in healthy fertile women.

PMID- 19386105
TI  - The effect of high frequency steep pulsed electric fields on in vitro and in vivo
      antitumor efficiency of ovarian cancer cell line skov3 and potential use in
      electrochemotherapy.
AB  - BACKGROUND: Patients received electrochemotherapy often associated with
      unpleasant sensations mainly result from low-frequency electric pulse induced
      muscle contractions. Increasing the repetition frequency of electric pulse can
      reduce unpleasant sensations. However, due to the specificity of SPEF, frequency
      related antitumor efficiency need to be further clarified. The aim of this study
      was to compare in vitro cytotoxic and in vivo antitumor effect on ovarian cancer
      cell line SKOV3 by SPEF with different repetition frequencies. Explore potential
      benefits of using high frequency SPEF in order to be exploitable in
      electrochemotherapy. METHODS: For in vitro experiment, SKOV3 cell suspensions
      were exposed to SPEF with gradient increased frequencies (1, 60, 1000, 5000 Hz)
      and electric field intensity (50, 100, 150, 200, 250, 300, 350, 400 V/cm)
      respectively. For in vivo test, SKOV3 subcutaneous implanted tumor in BALB/c nude
      mice (nu/nu) were exposure to SPEF with gradient increased frequencies (1, 60,
      1000, 5000 Hz) and fixed electric field intensity (250 V/cm) (7 mice for each
      frequency and 7 for control). Antitumor efficiency was performed by in vitro
      cytotoxic assay and in vivo tumor growth inhibition rate, supplemented by
      histological and TEM observations. Data were analyzed using one-way ANOVA
      followed by the comparisons of multiple groups. RESULTS: SPEF with a given
      frequency and appropriate electric field intensity could achieve similar
      cytotoxicity until reached a plateau of maximum cytotoxicity (approx. 100%). SPEF
      with different frequencies had significant antitumor efficiency in comparison to
      the control group (P < 0.05). However, there was no difference in tumor responses
      among test groups (P > 0.05). Histological and TEM observations demonstrated
      obvious cell damages in response to SPEF exposure. Furthermore, SPEF with 5 kHz
      could induce apoptosis under TEM observations both in vitro and in vivo.
      CONCLUSION: SPEF with high frequency could also achieve similar antitumor
      efficiency which can be used to reduce unpleasant sensations in tumor electrical
      treatment. Our research proposed potential applications of using high frequency
      SPEF in clinical cancer treatment.

PMID- 19386106
TI  - How parents choose to use CAM: a systematic review of theoretical models.
AB  - BACKGROUND: Complementary and Alternative Medicine (CAM) is widely used
      throughout the UK and the Western world. CAM is commonly used for children and
      the decision-making process to use CAM is affected by numerous factors. Most
      research on CAM use lacks a theoretical framework and is largely based on
      bivariate statistics. The aim of this review was to identify a conceptual model
      which could be used to explain the decision-making process in parental choice of
      CAM. METHODS: A systematic search of the literature was carried out. A two-stage
      selection process with predetermined inclusion/exclusion criteria identified
      studies using a theoretical framework depicting the interaction of psychological
      factors involved in the CAM decision process. Papers were critically appraised
      and findings summarised. RESULTS: Twenty two studies using a theoretical model to
      predict CAM use were included in the final review; only one examined child use.
      Seven different models were identified. The most commonly used and successful
      model was Andersen's Sociobehavioural Model (SBM). Two papers proposed
      modifications to the SBM for CAM use. Six qualitative studies developed their own
      model. CONCLUSION: The SBM modified for CAM use, which incorporates both
      psychological and pragmatic determinants, was identified as the best conceptual
      model of CAM use. This model provides a valuable framework for future research,
      and could be used to explain child CAM use. An understanding of the decision
      making process is crucial in promoting shared decision making between healthcare
      practitioners and parents and could inform service delivery, guidance and policy.

PMID- 19386107
TI  - Bone sialoprotein does not interact with pro-gelatinase A (MMP-2) or mediate MMP
      2 activation.
AB  - BACKGROUND: A recent model for activation of the zymogen form of matrix
      metalloproteinase 2 (MMP-2, also known as gelatinase A) has suggested that
      interactions between the SIBLING protein bone sialoprotein (BSP) and MMP-2 leads
      to conformational change in MMP-2 that initiates the conversion of the pro-enzyme
      into a catalytically active form. This model is particularly relevant to cancer
      cell metastasis to bone since BSP, bound to the alphavbeta3 integrin through its
      arginine-glycine-aspartic acid motif, could recruit MMP-2 to the cell surface.
      METHODS: We critically assessed the relationship between BSP and proMMP-2 and its
      activation using various forms of recombinant and purified BSP and MMP-2.
      Gelatinase and collagenase assays, fluorescence binding assays, real-time PCR,
      cell culture and pull-down assays were employed to test the model. RESULTS:
      Studies with a fluorogenic substrate for MMP-2 showed no activation of proMMP-2
      by BSP. Binding and pull-down assays demonstrated no interaction between MMP-2
      and BSP. While BSP-mediated invasiveness has been shown to depend on its integrin
      binding RGD sequence, analysis of proMMP-2 activation and the level of membrane
      type 1 (MT1)-MMP in cells grown on a BSP substratum showed that the BSP
      alphavbeta3 integrin interaction does not induce the expression of MT1-MMP.
      CONCLUSION: These studies do not support a role for BSP in promoting metastasis
      through interactions with pro-MMP-2.

PMID- 19386109
TI  - Estimating the probability of stroke in Korean hypertensive patients visiting
      tertiary hospitals using a risk profile from the Framingham study.
AB  - BACKGROUND: Hypertension is the most important single modifiable risk factor for
      stroke. We investigated the distribution of stroke risk factors and 10-year
      probability of stroke in Korean hypertensive patients. METHODS: A total of 1,402
      hypertensive patients treated by cardiology departments at 37 general hospitals
      nationwide were enrolled. Risk factors for stroke were evaluated using a series
      of laboratory tests and physical examinations, and the 10-year probability of
      stroke was determined by applying the Framingham stroke risk equation. RESULTS:
      The proportion of patients who have uncontrolled hypertension despite use of
      antihypertensives was 37.2% (37.2% women, 37.3% men, p = 0.990). The average 10
      year probability of stroke in hypertensive patients was 24.27% (24.17% women,
      24.39% men, p = 0.825), approximately 2.4 times higher than of the risk of stroke
      observed in the Korean Cancer Prevention Study [KCPS] cohort. The 10-year stroke
      probability in patients with hypertension increased in proportion to age. In
      patients for hypertension, the 10-year probability of stroke increased in
      proportion to blood pressure. CONCLUSION: Aggressive interventions are mandated
      to reduce blood pressure and alleviate the high risk of stroke in hypertensive
      patients.

PMID- 19386110
TI  - Serum procalcitonin for the early recognition of nosocomial infection in the
      critically ill patients: a preliminary report.
AB  - BACKGROUND: The usefulness of procalcitonin (PCT) measurement in critically ill
      medical patients with suspected nosocomial infection is unclear. The aim of the
      study was to assess PCT value for the early diagnosis of bacterial nosocomial
      infection in selected critically ill patients. METHODS: An observational cohort
      study in a 15-bed intensive care unit was performed. Seventy patients with either
      proven (n = 47) or clinically suspected but not confirmed (n = 23) nosocomial
      infection were included. Procalcitonin measurements were obtained the day when
      the infection was suspected (D0) and at least one time within the 3 previous days
      (D-3 to D0). Patients with proven infection were compared to those without. The
      diagnostic value of PCT on D0 was determined through the construction of the
      corresponding receiver operating characteristic (ROC) curve. In addition, the
      predictive value of PCT variations preceding the clinical suspicion of infection
      was assessed. RESULTS: PCT on D0 was the best predictor of proven infection in
      this population of ICU patients with a clinical suspicion of infection (AUROCC =
      0.80; 95% CI, 0.68-0.91). Thus, a cut-off value of 0.44 ng/mL provides
      sensitivity and specificity of 65.2% and 83.0%, respectively. Procalcitonin
      variation between D-1 and D0 was calculated in 45 patients and was also found to
      be predictive of nosocomial infection (AUROCC = 0.89; 95% CI, 0.79-0.98) with a
      100% positive predictive value if the +0.26 ng/mL threshold value was applied.
      Comparable results were obtained when PCT variation between D-2 and D0, or D-3
      and D0 were considered. In contrast, CRP elevation, leukocyte count and fever had
      a poor predictive value in our population. CONCLUSION: PCT monitoring could be
      helpful in the early diagnosis of nosocomial infection in the ICU. Both absolute
      values and variations should be considered and evaluated in further studies.

PMID- 19386108
TI  - Systems biology coupled with label-free high-throughput detection as a novel
      approach for diagnosis of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a treatable and preventable
      disease state, characterised by progressive airflow limitation that is not fully
      reversible. Although COPD is primarily a disease of the lungs there is now an
      appreciation that many of the manifestations of disease are outside the lung,
      leading to the notion that COPD is a systemic disease. Currently, diagnosis of
      COPD relies on largely descriptive measures to enable classification, such as
      symptoms and lung function. Here the limitations of existing diagnostic
      strategies of COPD are discussed and systems biology approaches to diagnosis that
      build upon current molecular knowledge of the disease are described. These
      approaches rely on new 'label-free' sensing technologies, such as high-throughput
      surface plasmon resonance (SPR), that we also describe.

PMID- 19386112
TI  - Road traffic injuries in one local health unit in the Lazio region: results of a
      surveillance system integrating police and health data.
AB  - OBJECTIVE: Different sources are available for the surveillance of Road Traffic
      injuries (RTI), but studied individually they present several limits. In this
      paper we present the results of a surveillance integrating healthcare data with
      the data gathered by the municipal police in the southeastern area of Rome
      (630,000 inhabitants) during the year 2003. METHODS: The Municipal police RTI
      reports, which list the exact location, circumstances and some risk factor of the
      crash, were searched in the emergency visit, hospitalization and mortality
      databases, to integrate them with the information on health consequences. A
      multivariate analysis was conducted to evaluate risk factors (crash
      circumstances, age ad gender of the casualty) associated with hospital admission
      following a RTI. Mapping of RTI locations was created. The locations with higher
      risk of accidents with severe health consequences and at higher risk for
      pedestrians were identified. RESULTS: According to police records 4571 RTI
      occurred in 2003, 75% of which led to emergency department admissions. Sixteen
      percent of these emergency visits ended in hospitalization, and 44 deaths were
      reported within 30 days of the event, most of which occurred in young men. The
      people with the highest risk of hospitalization after an RTI were the cyclists,
      pedestrians and followed by people on two-wheeled vehicles. The type of crash
      with the highest risk of hospitalization was head-on collision. Geographical
      analyses showed four clusters with higher severity of RTI. Specific attention was
      paid to pedestrian injuries. Analyzing the locations of RTIs involving
      pedestrians permitted us to rank the most dangerous streets. The roads at high
      risk for pedestrians identified problems in the bus stop constructions and in the
      placement of the zebra pedestrian crossings. CONCLUSION: This study proves the
      feasibility of an integrated surveillance system of RTI by using routinely
      collected local data. The high-risk locations identified with the geographic
      analyses method in this study highlighted infrastructural problems, suggesting
      immediate preventive interventions.

PMID- 19386113
TI  - The value of minilaparotomy for total hysterectomy for benign uterine disease: a
      comparative study with conventional Pfannenstiel and laparoscopic approaches.
AB  - BACKGROUND: The aim of this paper is to review and compare the results obtained
      using the Pfannenstiel, laparoscopy and minilaparotomy approaches for total
      hysterectomy procedure in relation to benign uterine diseases. METHODS: A
      retrospective data analysis was performed on 165 patients who underwent
      hysterectomy for benign uterine diseases at our centre during the period 2004 to
      2006. FINDINGS: The minilaparotomy procedure was the fastest procedure with a
      mean time of 73.4 minutes (range: 67.85 to 78.94 minutes, p < 0.001). Hospital
      stay was shortest for laparosopic procedure (mean time: 3.24 days, range: 2.86 to
      3.61 days) (p < 0.001). The rate of intraoperative and postoperative
      complications were not statistical different among three procedures. CONCLUSION:
      The minilaparotomy procedure offers a minimally invasive option for total
      hysterectomy due to benign uterine disease.

PMID- 19386111
TI  - Action to achieve smoke-free homes: an exploration of experts' views.
AB  - BACKGROUND: Smoking in the home is the major cause of exposure to second-hand
      smoke in children in the UK, particularly those living in low income households
      which have fewer restrictions on smoking in the home. Reducing children's
      exposure to second-hand smoke is an important public health and inequalities
      issue. Drawing on findings from a qualitative Scottish study, this paper
      identifies key issues and challenges that need to be considered when developing
      action to promote smoke-free homes at the national and local level. METHODS: Two
      panels of tobacco control experts (local and national) from Scotland considered
      the implications of the findings from a qualitative study of smokers and non
      smokers (who were interviewed about smoking in the home), for future action on
      reducing smoking in the home. RESULTS: Several key themes emerged through the
      expert panel discussions. These related to: improving knowledge about SHS among
      carers and professionals; the goal and approach of future interventions
      (incremental/harm reduction or total restrictions); the complexity of the
      interventions; and issues around protecting children. CONCLUSION: The expert
      panels were very aware of the sensitivities around the boundary between the
      'private' home and public health interventions; but also the lack of evidence on
      the relative effectiveness of specific individual and community approaches on
      increasing restrictions on smoking in the home. Future action on smoke-free homes
      needs to consider and address these complexities. In particular health
      professionals and other key stakeholders need appropriate training on the issues
      around smoking in the home and how to address these, as well as for more research
      to evaluate interventions and develop a more robust evidence base to inform
      effective action on this issue.

PMID- 19386114
TI  - Effect of sugar on male Anopheles gambiae mating performance, as modified by
      temperature, space, and body size.
AB  - BACKGROUND: Anopheles gambiae plant-sugar feeding was thought to be rare and
      physiologically optional. Unlike adult females, males have no alternative source
      of energy and soon die with only water, yet they might be competent to inseminate
      all females within their brief lifespan. This study was designed to detect
      sugar's effect, if any, on male performance. METHODS: Males with and without 20%
      sucrose were evaluated at two body sizes and two temperatures, 23 degrees and 27
      degrees C. Survival was recorded twice daily, and sexual behaviour was recorded
      each night after adult emergence. Insemination at a 2:1 male:female ratio was
      examined in three cage sizes, including walk-in mesocosms. RESULTS: Without
      sugar, males of both sizes lived longer at 23 degrees than 27 degrees C, and
      large males lived longer at each temperature. Survival of large males at low
      temperature averaged 3.7 days, small males at high temperature, 1.9 days. With
      sugar, males in all four treatments suffered minimal mortality. With sugar, in
      small cages, large males at 27 degrees C matured most rapidly. A few erected
      fibrillae and inseminated females on night 1. On night 2, maximal proportions
      erected fibrillae and swarmed, and over one-third of females became inseminated.
      Small sugar-fed males at 23 degrees C matured most slowly but had achieved nearly
      maximal levels of swarming by night 3. By night 5, small males had inseminated
      more than half the females, and large males had inseminated nearly all of them.
      Without sugar, large males progressed similarly during the first two nights. On
      night 3, however, the proportion erecting fibrillae and swarming declined
      precipitously at 27 degrees C, and to a lesser degree at 23 degrees C. Cumulative
      insemination never reached high levels. Small males never achieved high levels of
      fibrillar erection or swarming and inseminated few females, even at 23 degrees C.
      In larger cages and under more semi-natural conditions, regardless of body size,
      without sugar male insemination capacity was virtually nonexistent. CONCLUSION:
      Under some conditions, a limited number of sugar-deprived males can survive long
      enough to inseminate females. However, in nature males that cannot obtain sugar
      at frequent intervals will not be competitive with those that can, suggesting
      that male performance is closely tied to plant communities.

PMID- 19386115
TI  - Close phylogenetic relationship between Angolan and Romanian HIV-1 subtype F1
      isolates.
AB  - BACKGROUND: Here, we investigated the phylogenetic relationships of the HIV-1
      subtype F1 circulating in Angola with subtype F1 strains sampled worldwide and
      reconstructed the evolutionary history of this subtype in Central Africa.
      METHODS: Forty-six HIV-1-positive samples were collected in Angola in 2006 and
      subtyped at the env-gp41 region. Partial env-gp120 and pol-RT sequences and near
      full-length genomes from those env-gp41 subtype F1 samples were further
      generated. Phylogenetic analyses of partial and full-length subtype F1 strains
      isolated worldwide were carried out. The onset date of the subtype F1 epidemic in
      Central Africa was estimated using a Bayesian Markov chain Monte Carlo approach.
      RESULTS: Nine Angolan samples were classified as subtype F1 based on the analysis
      of the env-gp41 region. All nine Angolan sequences were also classified as
      subtype F1 in both env-gp120 and pol-RT genomic regions, and near full-length
      genome analysis of four of these samples confirmed their classification as "pure"
      subtype F1. Phylogenetic analyses of subtype F1 strains isolated worldwide
      revealed that isolates from the Democratic Republic of Congo (DRC) were the
      earliest branching lineages within the subtype F1 phylogeny. Most strains from
      Angola segregated in a monophyletic group together with Romanian sequences;
      whereas South American F1 sequences emerged as an independent cluster. The origin
      of the subtype F1 epidemic in Central African was estimated at 1958 (1934-1971).
      CONCLUSION: "Pure" subtype F1 strains are common in Angola and seem to be the
      result of a single founder event. Subtype F1 sequences from Angola are closely
      related to those described in Romania, and only distantly related to the subtype
      F1 lineage circulating in South America. Original diversification of subtype F1
      probably occurred within the DRC around the late 1950s.

PMID- 19386117
TI  - Awareness of benign paroxysmal positional vertigo in central Israel.
AB  - BACKGROUND: Despite its frequent occurrence and effective treatment options,
      benign paroxysmal positional vertigo (BPPV) still remains under-estimated in the
      community. METHODS: We reviewed referral letters and medical records of 120
      patients who were treated for BPPV at our Dizziness Clinic during the years 2006
      2008 and searched for factors that possibly contribute to missing this entity.
      RESULTS: The referral diagnosis could be clustered into four groups: BPPV
      (25.6%), further unspecified vertigo (36.6%), dizziness (27.5%) and other (10%).
      BPPV was recognized more frequently by ENT doctors than by other
      specialists.Patients referred with the correct diagnosis of BPPV were
      significantly younger and the duration of their symptoms shorter than in other
      referral groups. Patients in the distinct referral groups did not differ in the
      presence of autonomic symptoms or a history of another serious disease. A history
      typical of BPPV could be obtained in all but 11 patients, but position dependence
      was noted by the referring physician only in 55 patients, 31 of them correctly
      assigned as possible BPPV. Only in two patients was the Dix-Hallpike test
      performed. Thirty two patients were diagnosed with BPPV in the past, but this did
      not influence the recognition of the recurrence of this clinical entity. About
      40% of patients had an audiogram and/or brainstem auditory evoked potentials.
      Electronystagmography was performed in 7.5% and brain imaging in 14% of patients
      before referral. CONCLUSION: Our results show that BPPV is still an under
      recognized entity.Education and the demand on specialists to learn how to treat
      BPPV, could improve the situation.

PMID- 19386116
TI  - Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and
      invasion in ovarian cancer cells.
AB  - BACKGROUND: Ovarian cancer is the leading cause of mortality from gynecological
      malignancies, often undetectable in early stages. The difficulty of detecting the
      disease in its early stages and the propensity of ovarian cancer cells to develop
      resistance to known chemotherapeutic treatments dramatically decreases the 5-year
      survival rate. Chemotherapy with paclitaxel after surgery increases median
      survival only by 2 to 3 years in stage IV disease highlights the need for more
      effective drugs. The human immunodeficiency virus (HIV) infection is
      characterized by increased risk of several solid tumors due to its inherent
      nature of weakening of immune system. Recent observations point to a lower
      incidence of some cancers in patients treated with protease inhibitor (PI)
      cocktail treatment known as HAART (Highly Active Anti-Retroviral Therapy).
      RESULTS: Here we show that ritonavir, a HIV protease inhibitor effectively
      induced cell cycle arrest and apoptosis in ovarian cell lines MDH-2774 and SKOV-3
      in a dose dependent manner. Over a 3 day period with 20 muM ritonavir resulted in
      the cell death of over 60% for MDAH-2774 compared with 55% in case of SKOV-3 cell
      line. Ritonavir caused G1 cell cycle arrest of the ovarian cancer cells, mediated
      by down modulating levels of RB phosphorylation and depleting the G1 cyclins,
      cyclin-dependent kinase and increasing their inhibitors as determined by gene
      profile analysis. Interestingly, the treatment of ritonavir decreased the amount
      of phosphorylated AKT in a dose-dependent manner. Furthermore, inhibition of AKT
      by specific siRNA synergistically increased the efficacy of the ritonavir-induced
      apoptosis. These results indicate that the addition of the AKT inhibitor may
      increase the therapeutic efficacy of ritonavir. CONCLUSION: Our results
      demonstrate a potential use of ritonavir for ovarian cancer with additive effects
      in conjunction with conventional chemotherapeutic regimens. Since ritonavir is
      clinically approved for human use for HIV, drug repositioning for ovarian cancer
      could accelerate the process of traditional drug development. This would reduce
      risks, limit the costs and decrease the time needed to bring the drug from bench
      to bedside.

PMID- 19386119
TI  - Patient-physician interaction in general practice and health inequalities in a
      multidisciplinary study: design, methods and feasibility in the French INTERMEDE
      study.
AB  - BACKGROUND: The way in which patients and their doctors interact is a potentially
      important factor in optimal communication during consultations as well as
      treatment, compliance and follow-up care. The aim of this multidisciplinary study
      is to use both qualitative and quantitative methods to explore the 'black box'
      that is the interaction between the two parties during a general practice
      consultation, and to identify factors therein that may contribute to producing
      health inequalities. This paper outlines the original multidisciplinary
      methodology used, and the feasibility of this type of study. METHODS AND DESIGN:
      The study design combines methodologies on two separate samples in two phases.
      Firstly, a qualitative phase collected ethnographical and sociological data
      during consultation, followed by in-depth interviews with both patients and
      doctors independently. Secondly, a quantitative phase on a different sample of
      patients and physicians collected data via several questionnaires given to
      patients and doctors consisting of specific 'mirrored' questions asked post
      consultation, as well as collecting information on patient and physician
      characteristics. DISCUSSION: The design and methodology used in this study were
      both successfully implemented, and readily accepted by doctors and patients
      alike. This type of multidisciplinary study shows great potential in providing
      further knowledge into the role of patient/physician interaction and its
      influence on maintaining or producing health inequalities. The next challenge in
      this study will be implementing the multidisciplinary approach during the data
      analysis.

PMID- 19386118
TI  - Pregnancy in the mature adult mouse does not alter the proportion of mammary
      epithelial stem/progenitor cells.
AB  - INTRODUCTION: In humans, an early full-term pregnancy reduces lifetime breast
      cancer risk by up to 50% whereas a later pregnancy (>35 years old) can increase
      lifetime risk. Several mechanisms have been suggested, including changes in
      levels of circulating hormones, changes in the way the breast responds to these
      hormones, changes in gene expression programmes which may alter susceptibility to
      transformation and changes to mammary stem cell numbers or behaviour. Previous
      studies have shown that the mammary tissue isolated from both virgin and parous
      mice has the ability to repopulate a cleared mammary fat pad in transplant
      experiments. Limited dilution transplant assays have demonstrated that early
      pregnancy (at 5 weeks of age) reduces stem/progenitor cell numbers in the mouse
      mammary epithelium by twofold. However, the effects on stem/progenitor cell
      numbers in the mammary epithelium of a pregnancy in older animals have not yet
      been tested. METHODS: Mice were put through a full-term pregnancy at 9 weeks of
      age, when the mammary epithelium is mature. The total mammary epithelium was
      purified from parous 7-week post-lactation and age-matched virgin mice and
      analysed by flow cytometry and limiting dilution cleared fat pad transplants.
      RESULTS: There were no significant differences in the proportions of different
      mammary epithelial cell populations or numbers of CD24(+/Low) Sca-1- CD49f(High)
      cells (stem cell enriched basal mammary epithelial compartment). There was no
      significant difference in stem/progenitor cell frequency based on limiting
      dilution transplants between the parous and age-matched virgin epithelium.
      CONCLUSIONS: Although differences between parous and virgin mammary epithelium at
      later time points post lactation or following multiple pregnancies cannot be
      ruled out, there are no differences in stem/progenitor cell numbers between
      mammary epithelium isolated from parous animals which were mated at 9 weeks old
      and virgin animals. However, a recent report has suggested that animals that were
      mated at 5 weeks old have a twofold reduction in stem/progenitor cell numbers.
      This is of interest given the association between early, but not late, pregnancy
      and breast cancer risk reduction in humans. However, a mechanistic connection
      between stem cell numbers and breast cancer risk remains to be established.

PMID- 19386120
TI  - Effect of conjugated linoleic acids from beef or industrial hydrogenation on
      growth and adipose tissue characteristics of rats.
AB  - BACKGROUND: The conjugated linoleic acid (CLA) content of beef can be increased
      by supplementing appropriate beef cattle diets with vegetable oil or oil seed.
      Yet the effect of consumption of such beef on adipose tissue characteristics is
      unclear, thus the study was conducted to compare adipose tissue responses of rats
      to diets containing beef from steers either not provided or provided the oil
      supplements to alter CLA composition of the fat in muscle. METHODS: Effects of
      feeding synthetic (industrial hydrogenation) CLA or CLA from beef on growth and
      adipose tissue responses of weanling, male, Wistar rats (n = 56; 14 per treatment
      diet) were investigated in a completely randomized design experiment. Diets were:
      control (CON) diet containing casein and soybean oil, synthetic CLA (SCLA) diet;
      where 1.69% synthetic CLA replaced soybean oil, two beef-diets; CONM and CLAM,
      containing freeze dried beef from steers either not fed or fed 14% sunflower
      seeds to increase CLA content of beef. Diets were isonitrogenous (20% protein)
      and isocaloric. Rat weights and ad libitum intakes were recorded every 2 wk.
      After 9 wk, rats were fasted for 24 h, blood sampled by heart puncture,
      sacrificed, tissue and organs were harvested and weights recorded. The adipose
      tissue responses with regard to cellularity and fatty acid compositions of
      retroperitoneal and inguinal adipose tissue were determined. RESULTS: Body
      weights and gains were comparable, but organ weights as percent of body weight
      were greater for rats fed SCLA than CONM. Fasting blood glucose concentration was
      lower (p < 0.01) in rats fed SCLA than those fed CONM or CLAM. Retroperitoneal
      and inguinal fat weights, as percent of body weight were greater (p < 0.01) in
      rats fed CONM or CLAM than those fed CON or SCLA diets. Adipocyte numbers were
      least in retroperitoneal tissue of rats fed SCLA, while inguinal tissue cell
      density and total number were lower (p = 0.02) in rats fed CLAM (7.26 x 107
      cells/g and 8.03 x 108 cells) than those fed CONM (28.88 x 107 cells/g and 32.05
      x 108 cells, respectively). CONCLUSION: Study suggests that dietary CLA either as
      synthetic or high CLA-beef may alter adipose tissue characteristics by decreasing
      the number of adipocytes and by decreasing the size of the tissue.

PMID- 19386121
TI  - Hunting strategies used in the semi-arid region of northeastern Brazil.
AB  - Hunting for wild animals is stimulated by the many different human uses of faunal
      resources, and these animals constitute important subsistence items in local
      communities in the Caatinga region. In order to gain access to these resources,
      hunters have developed a series of techniques and strategies that are described
      in the present work. The principal hunting techniques encountered were: waiting,
      especially directed towards hunting diurnal birds; calling ("arremedo"), a
      technique in which the hunters imitate the animal's call to attract it to close
      range; hunting with dogs, a technique mostly used for capturing mammals;
      tracking, a technique used by only a few hunters who can recognize and follow
      animal tracks; and "facheado", in which the hunters go out at night with lanterns
      to catch birds in their nests. Additionally, many animal species are captured
      using mechanical traps. The types of traps used by the interviewees were: dead
      fall traps ("quixo"), iron-jaw snap traps ("arataca"), wooden cages with bait
      ("arapuca"), iron-cage traps ("gaiola'), "visgo", multi-compartment bird cages
      ("alcapao"), buried ground traps with pivoted tops ("fojo"), and nooses and cages
      for carnivorous. The choice of which technique to use depends on the habits of
      the species being hunted, indicating that the hunters possess a wide knowledge of
      the biology of these animals. From a conservation perspective, active hunting
      techniques (waiting, imitation, hunting with dogs, and "facheado") have the
      greatest impact on the local fauna. The use of firearm and dogs brought greater
      efficiency to hunting activities. Additional studies concerning these hunting
      activities will be useful to contribute to proposals for management plans
      regulating hunting in the region - with the objective of attaining sustainable
      use of faunal resources of great importance to the local human communities.

PMID- 19386122
TI  - Cloning of transgenic tobacco BY-2 cells; an efficient method to analyse and
      reduce high natural heterogeneity of transgene expression.
AB  - BACKGROUND: Phenotypic characterization of transgenic cell lines, frequently used
      in plant biology studies, is complicated because transgene expression in
      individual cells is often heterogeneous and unstable. To identify the sources and
      to reduce this heterogeneity, we transformed tobacco (Nicotiana tabacum L.) BY-2
      cells with a gene encoding green fluorescent protein (GFP) using Agrobacterium
      tumefaciens, and then introduced a simple cloning procedure to generate cell
      lines derived from the individual transformed cells. Expression of the transgene
      was monitored by analysing GFP fluorescence in the cloned lines and also in lines
      obtained directly after transformation. RESULTS: The majority ( approximately
      90%) of suspension culture lines derived from calli that were obtained directly
      from transformation consisted of cells with various levels of GFP fluorescence.
      In contrast, nearly 50% of lines generated by cloning cells from the primary
      heterogeneous suspensions consisted of cells with homogenous GFP fluorescence.
      The rest of the lines exhibited "permanent heterogeneity" that could not be
      resolved by cloning. The extent of fluorescence heterogeneity often varied, even
      among genetically identical clones derived from the primary transformed lines. In
      contrast, the offspring of subsequent cloning of the cloned lines was uniform,
      showing GFP fluorescence intensity and heterogeneity that corresponded to the
      original clone. CONCLUSION: The results demonstrate that, besides genetic
      heterogeneity detected in some lines, the primary lines often contained a mixture
      of epigenetically different cells that could be separated by cloning. This
      indicates that a single integration event frequently results in various heritable
      expression patterns, which are probably accidental and become stabilized in the
      offspring of the primary transformed cells early after the integration event.
      Because heterogeneity in transgene expression has proven to be a serious problem,
      it is highly advisable to use transgenes tagged with a visual marker for BY-2
      transformation. The cloning procedure can be used not only for efficient
      reduction of expression heterogeneity of such transgenes, but also as a useful
      tool for studies of transgene expression and other purposes.

PMID- 19386123
TI  - The zinc finger protein Zn72D and DEAD box helicase Belle interact and control
      maleless mRNA and protein levels.
AB  - BACKGROUND: The Male Specific Lethal (MSL) complex is enriched on the single X
      chromosome in male Drosophila cells and functions to upregulate X-linked gene
      expression and equalize X-linked gene dosage with XX females. The zinc finger
      protein Zn72D is required for productive splicing of the maleless (mle)
      transcript, which encodes an essential subunit of the MSL complex. In the absence
      of Zn72D, MLE levels are decreased, and as a result, the MSL complex no longer
      localizes to the X chromosome and dosage compensation is disrupted. To understand
      the molecular basis of Zn72D function, we identified proteins that interact with
      Zn72D. RESULTS: Among several proteins that associate with Zn72D, we found the
      DEAD box helicase Belle (Bel). Simultaneous knockdown of Zn72D and bel restored
      MSL complex localization to the X chromosome and dosage compensation. MLE protein
      was restored to 70% of wild-type levels, although the level of productively
      spliced mle transcript was still four-fold lower than in wild-type cells. The
      increase in production of MLE protein relative to the amount of correctly spliced
      mle mRNA could not be attributed to an alteration in MLE stability. CONCLUSION:
      These data indicate that Zn72D and Bel work together to control mle splicing and
      protein levels. Thus Zn72D and Bel may be factors that coordinate splicing and
      translational regulation.

PMID- 19386124
TI  - Conserved amino acid markers from past influenza pandemic strains.
AB  - BACKGROUND: Finding the amino acid mutations that affect the severity of
      influenza infections remains an open and challenging problem. Of special interest
      is better understanding how current circulating influenza strains could evolve
      into a new pandemic strain. Influenza proteomes from distinct viral phenotype
      classes were searched for class specific amino acid mutations conserved in past
      pandemics, using reverse engineered linear classifiers. RESULTS: Thirty-four
      amino acid markers associated with host specificity and high mortality rate were
      found. Some markers had little impact on distinguishing the functional classes by
      themselves, however in combination with other mutations they improved class
      prediction. Pairwise combinations of influenza genomes were checked for
      reassortment and mutation events needed to acquire the pandemic conserved
      markers. Evolutionary pathways involving H1N1 human and swine strains mixed with
      avian strains show the potential to acquire the pandemic markers with a double
      reassortment and one or two amino acid mutations. CONCLUSION: The small mutation
      combinations found at multiple protein positions associated with viral phenotype
      indicate that surveillance tools could monitor genetic variation beyond single
      point mutations to track influenza strains. Finding that certain strain
      combinations have the potential to acquire pandemic conserved markers through a
      limited number of reassortment and mutation events illustrates the potential for
      reassortment and mutation events to lead to new circulating influenza strains.

PMID- 19386125
TI  - Oleate lipase activity in Gardnerella vaginalis and reconsideration of existing
      biotype schemes.
AB  - BACKGROUND: Gardnerella vaginalis is a facultative gram positive organism that
      requires subculture every 1-2 days to maintain viability. It has been linked with
      bacterial vaginosis (BV), a syndrome that has been associated with increased risk
      for preterm delivery, pelvic inflammatory disease and HIV acquisition. About 10%
      of the G. vaginalis isolates have been reported to produce sialidase, but there
      have not been any studies relating sialidase production and biotype. Sialidase
      activity is dramatically increased in the vaginal fluid of women with BV and
      bacterial sialidases have been shown to increase the infectivity of HIV in vitro.
      There are 8 different biotypes of G. vaginalis. Biotypes 1-4 produce lipase and
      were reported to be associated with BV and the association of these biotypes with
      BV is under dispute. Other studies have demonstrated that G. vaginalis biotype 1
      can stimulate HIV-1 production. Because of the discrepancies in the literature we
      compared the methods used to biotype G. vaginalis and investigated the
      relationship of biotype and sialidase production. RESULTS: A new medium for
      maintenance of Gardnerella vaginalis which allows survival for longer than one
      week is described. Some isolates only grew well under anaerobic conditions.
      Sialidase producing isolates were observed in 5 of the 6 biotypes tested. Using 4
      methylumbelliferyl-oleate to determine lipase activity, instead of egg yolk agar,
      resulted in erroneous biotypes and does not provide reliable results. CONCLUSION:
      Previous studies associating G. vaginalis biotype with bacterial vaginosis were
      methodologically flawed, suggesting there is not an association of G. vaginalis
      biotypes and bacterial vaginosis. Sialidase activity was observed in 5 of the 8
      biotypes.

PMID- 19386126
TI  - Validation of spinal motion with the spine reposition sense device.
AB  - BACKGROUND: A sagittal plane spine reposition sense device (SRSD) has been
      developed. Two questions were addressed with this study concerning the new SRSD:
      1) whether spine movement was occurring with the methodology, and 2) where
      movement was taking place. METHODS: Sixty-five subjects performed seven trials of
      repositioning to a two-thirds full flexion position in sitting with X and Y
      displacement measurements taken at the T4 and L3 levels. The thoracolumbar angle
      between the T4 and the L3 level was computed and compared between the positions
      tested. A two (vertebral level of thoracic and lumbar) by seven (trials) mixed
      model repeated measures ANOVA indicated whether significant differences were
      present between the thoracic (T4) and lumbar (L3) angular measurements. RESULTS:
      Calculated thoracolumbar angles between T4 and L3 were significantly different
      for all positions tested indicating spinal movement was occurring with testing.
      No interactions were found between the seven trials and the two vertebral levels.
      No significant findings were found between the seven trials but significant
      differences were found between the two vertebral levels. CONCLUSION: This study
      indicated spine motion was taking place with the SRSD methodology and movement
      was found specific to the lumbar spine. These findings support utilizing the SRSD
      to evaluate changes in spine reposition sense during future intervention studies
      dealing with low back pain.

PMID- 19386127
TI  - Effect of optically modified polyethylene terephthalate fiber socks on chronic
      foot pain.
AB  - BACKGROUND: Increasing experimental and clinical evidence suggests that
      illumination of the skin with relatively low intensity light may lead to
      therapeutic results such as reduced pain or improved wound healing. The goal of
      this study was to evaluate prospectively whether socks made from polyethylene
      terephthalate (PET) incorporating optically active particles (Celliant)
      ameliorates chronic foot pain resulting from diabetic neuropathy or other
      disorders. Such optically modified fiber is thought to modify the illumination of
      the skin in the visible and infrared portions of the spectrum, and consequently
      reduce pain. METHODS: A double-blind, randomized trial with 55 subjects (38 men,
      17 women) enrolled (average age 59.7 +/- 11.9 years), 26 with diabetic neuropathy
      and 29 with other pain etiologies. Subjects twice completed the Visual Analogue
      Scale (VAS), Brief Pain Inventory (BPI), McGill Pain Questionnaire (MPQ), and SF
      36 a week apart (W(1+2)) before receiving either control or Celliant socks. The
      same questionnaires were answered again one and two weeks (W(3+4)) later. The
      questionnaires provided nine scores for analyzing pain reduction: one VAS score,
      two BPI scores, five MPQ scores, and the bodily pain score on the SF-36. Mean
      W(1+2) and W(3+4) scores were compared to measure pain reduction. RESULTS: More
      pain reduction was reported by Celliant subjects for 8 of the 9 pain questions
      employed, with a significant (p = 0.043) difference between controls and Celliant
      for McGill question III. In neuropathic subjects, Celliant caused more pain
      reduction in 6 of the 9 questions, but not significantly. In non-neuropathic
      subjects 8 of 9 questions showed more pain reduction with the Celliant socks.
      CONCLUSION: Socks with optically modified PET (Celliant) appear to have a
      beneficial impact on chronic foot pain. The mechanism could be related to the
      effects seen with illumination of tissues with visible and infrared light. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00458497.

PMID- 19386128
TI  - Individualized therapies in colorectal cancer: KRAS as a marker for response to
      EGFR-targeted therapy.
AB  - Individualized therapies that are tailored to a patient's genetic composition
      will be of tremendous value for treatment of cancer. Recently, Kirsten ras (KRAS)
      status has emerged as a predictor of response to epidermal growth factor receptor
      (EGFR) targeted therapies. In this article, we will discuss targeted therapies
      for colorectal cancers (CRC) based on EGFR signaling pathway and review published
      data about the potential usefulness of KRAS as a biological marker for response
      to these therapies. Results from relevant studies published since 2005 and
      unpublished results presented at national meetings were retrieved and summarized.
      These studies reflected response (or lack of response) to EGFR-targeted therapies
      in patients with metastatic CRC as a function of KRAS status. It has become clear
      that patients with colorectal cancer whose tumor has an activating mutation in
      KRAS do not respond to monoclonal antibody therapies targeting EGFR. It should
      now become a standard practice that any patients being considered for EGFR
      targeted therapies have their tumors tested for KRAS status and only those with
      wild-type KRAS being offered such therapies.

PMID- 19386129
TI  - Endometrial thickness, Caucasian ethnicity, and age predict clinical pregnancy
      following fresh blastocyst embryo transfer: a retrospective cohort.
AB  - BACKGROUND: In-vitro fertilization (IVF) with blastocyst as opposed to cleavage
      stage embryos has been advocated to improve success rates. Limited information
      exists on which to predict which patients undergoing blastocyst embryo transfer
      (BET) will achieve pregnancy. This study's objective was to evaluate the
      predictive value of patient and cycle characteristics for clinical pregnancy
      following fresh BET. METHODS: This was a retrospective cohort study from 2003
      2007 at an academic assisted reproductive program. 114 women with infertility
      underwent fresh IVF with embryo transfer. We studied patients undergoing transfer
      of embryos at the blastocyst stage of development. Our main outcome of interest
      was clinical pregnancy. Clinical pregnancy and its associations with patient
      characteristics (age, body mass index, FSH, ethnicity) and cycle parameters
      (thickness of endometrial stripe, number eggs, available cleaving embryos, number
      blastocysts available, transferred, and cryopreserved, and embryo quality) were
      examined using Student's T test and Mann-Whitney-U tests as appropriate.
      Multivariable logistic regression models were created to determine independent
      predictors of CP following BET. Receiver Operating Characteristic analyses were
      used to determine the optimal thickness of endometrial stripe for predicting
      clinical pregnancy. RESULTS: Patients achieving clinical pregnancy demonstrated a
      thicker endometrial stripe and were younger preceding embryo transfer. On
      multivariable logistic regression analyses, Caucasian ethnicity (OR 2.641, 95% CI
      1.054-6.617), thickness of endometrial stripe, (OR 1.185, 95% CI 1.006-1.396) and
      age (OR 0.879, 95% CI 0.789-0.980) predicted clinical pregnancy. By receiver
      operating characteristic analysis, endometrial stripe >or= 9.4 mm demonstrated a
      sensitivity of 83% for predicting clinical pregnancy following BET. CONCLUSION:
      In a cohort of patients undergoing fresh BET, thicker endometrial stripe,
      Caucasian ethnicity, and younger age are positive predictors of clinical
      pregnancy after fresh BET. These findings may be useful in clinical management of
      infertile patients undergoing fresh BET cycles.

PMID- 19386130
TI  - Comparative study of the persistence of anti-HIV activity of deoxynucleoside HIV
      reverse transcriptase inhibitors after removal from culture.
AB  - BACKGROUND: Most in vitro assays of drug potency may not adequately predict the
      performance in vivo. Methods to assess the persistence of antiviral activity of
      deoxynucleoside analogs, which require intracellular activation to the active
      metabolites that can persist in cells, will be important for designing dosages,
      combination regimens, and assessing treatment compliance. Using an HIV-IIIB/TZM
      bl indicator cell culture system, we assessed the ability of an inhibitor to
      protect cells from infection and to delay viral rebound after removal of
      inhibitor from culture. RESULTS: The order of protection of cells from HIV
      infection was 4'-Ed4T > LFD4C > DDI > D4T > 3TC > AZT > FTC > NVP. The fold
      increase in EC50 to delay viral rebound was DDI < 4'-Ed4T < LFD4C < FTC < D4T <
      3TC < NVP < AZT. The ranking of persistence of anti-HIV activity of the
      inhibitors based on the two-component assay was DDI > 4'-Ed4T > LFD4C > FTC = D4T
      > 3TC > NVP > AZT. CONCLUSION: The persistence ranking was derived from assays
      based on measures of single viral replication-cycle and cumulative inhibition at
      multiple time-points. Therefore, a better indicator of the pharmacodynamic
      property of an inhibitor. The persistence of anti-HIV activity assay may
      complement in vitro potency assays to better predict in vivo performance of
      nucleoside analogs.

PMID- 19386131
TI  - Research collaboration in Tehran University of Medical Sciences: two decades
      after integration.
AB  - BACKGROUND: In 1985 medical schools were integrated into the Ministry of Health,
      and the Ministry of Health and Medical Education was created in Iran. Under this
      infrastructure education, research and service provision are unified, and it is
      expected that collaboration between researchers and decision makers become easier
      in such an integrated context.The question here is how the researchers behavior
      in the biggest medical university of the country towards collaboration is, i.e.
      how much do decision makers participate in different stages of research? Which
      factors affect it? METHODOLOGY: The samples under study were all Tehran
      University of Medical Sciences (TUMS) completed research projects that had gotten
      grants in 2004 and were over by the time this study was done. Two questionnaires
      were designed for this study: i) the research checklist which was filled for 301
      projects, ii) the researcher's questionnaire, which was sent to principle
      investigators, 208 of which were collected. Multiple linear regression analysis
      was used for evaluating the potential factors affecting individuals
      'collaboration score'. RESULTS: Only 2.2 percent of TUMS' projects initiated in
      2004 have had collaboration as a joint PI or co-investigator from non-academic
      organizations. The principle investigators mean collaboration score was 2.09,
      where 6 was the total score. So the collaboration score obtained was 35%. The
      'type of research' had significant association with the collaboration score which
      is shown in the linear regression; collaboration was seen more in clinical (p =
      0.007) and health system researches (p = 0.001) as compared to basic research.
      CONCLUSION: The present study shows that not many individuals collaborated as co
      investigators from outside the university. This finding shows that research
      policy makers need to introduce interventions in this field. And assessment of
      barriers to collaboration and its facilitating factors should be considered in
      order to make it actually happen.

PMID- 19386132
TI  - Cellular and subcellular localization of Marlin-1 in the brain.
AB  - BACKGROUND: Marlin-1 is a microtubule binding protein that associates
      specifically with the GABAB1 subunit in neurons and with members of the Janus
      kinase family in lymphoid cells. In addition, it binds the molecular motor
      kinesin-I and nucleic acids, preferentially single stranded RNA. Marlin-1 is
      expressed mainly in the central nervous system but little is known regarding its
      cellular and subcellular distribution in the brain. RESULTS: Here we have studied
      the localization of Marlin-1 in the rodent brain and cultured neurons combining
      immunohistochemistry, immunofluorescence and pre-embedding electron microscopy.
      We demonstrate that Marlin-1 is enriched in restricted areas of the brain
      including olfactory bulb, cerebral cortex, hippocampus and cerebellum. Marlin-1
      is abundant in dendrites and axons of GABAergic and non-GABAergic hippocampal
      neurons. At the ultrastructural level, Marlin-1 is present in the cytoplasm and
      the nucleus of CA1 neurons in the hippocampus. In the cytoplasm it associates to
      microtubules in the dendritic shaft and occasionally with the Golgi apparatus,
      the endoplasmic reticulum (ER) and dendritic spines. In the nucleus, clusters of
      Marlin-1 associate to euchromatin. CONCLUSION: Our results demonstrate that
      Marlin-1 is expressed in discrete areas of the brain. They also confirm the
      microtubule association at the ultrastructural level in neurons. Together with
      the abundance of the protein in dendrites and axons they are consistent with the
      emerging role of Marlin-1 as an intracellular protein linking the cytoskeleton
      and transport. Our study constitutes the first detailed description of the
      cellular and subcellular distribution of Marlin-1 in the brain. As such, it will
      set the basis for future studies on the functional implications of Marlin-1 in
      protein trafficking.

PMID- 19386134
TI  - Maternal mortality in the informal settlements of Nairobi city: what do we know?
AB  - BACKGROUND: Current estimates of maternal mortality ratios in Kenya are at least
      as high as 560 deaths per 100,000 live births. Given the pervasive poverty and
      lack of quality health services in slum areas, the maternal mortality situation
      in this setting can only be expected to be worse. With a functioning health care
      system, most maternal deaths are avoidable if complications are identified early.
      A major challenge to effective monitoring of maternal mortality in developing
      countries is the lack of reliable data since vital registration systems are
      either non-existent or under-utilized. In this paper, we estimated the burden and
      identified causes of maternal mortality in two slums of Nairobi City, Kenya.
      METHODS: We used data from verbal autopsy interviews conducted on nearly all
      female deaths aged 15-49 years between January 2003 and December 2005 in two slum
      communities covered by the Nairobi Urban Health and Demographic Surveillance
      System (NUHDSS). In describing the distribution of maternal deaths by cause, we
      examined maternal and late maternal deaths according to the ICD-10
      classification. Additionally we used data from a survey of health care facilities
      that serve residents living in the surveillance areas for 2004-2005 to examine
      causes of maternal death. RESULTS: The maternal mortality ratio for the two
      Nairobi slums, for the period January 2003 to December 2005, was 706 maternal
      deaths per 100,000 live births. The major causes of maternal death were: abortion
      complications, hemorrhage, sepsis, eclampsia, and ruptured uterus. Only 21% of
      the 29 maternal deaths delivered or aborted with assistance of a health
      professional. The verbal autopsy tool seems to capture more abortion related
      deaths compared to health care facility records. Additionally, there were 22 late
      maternal deaths (maternal deaths between 42 days and one year of pregnancy
      termination) most of which were due to HIV/AIDS and anemia. CONCLUSION: Maternal
      mortality ratio is high in the slum population of Nairobi City. The Demographic
      Surveillance System and verbal autopsy tool may provide the much needed data on
      maternal mortality and its causes in developing countries. There is urgent need
      to address the burden of unwanted pregnancies and unsafe abortions among the
      urban poor. There is also need to strengthen access to HIV services alongside
      maternal health services since HIV/AIDS is becoming a major indirect cause of
      maternal deaths.

PMID- 19386133
TI  - End-of-life issues in the acute and critically ill patient.
AB  - The challenges of end-of-life care require emergency physicians to utilize a
      multifaceted and dynamic skill set. Such skills include medical therapies to
      relieve pain and other symptoms near the end-of-life. Physicians must also
      demonstrate aptitude in comfort care, communication, cultural competency, and
      ethical principles. It is imperative that emergency physicians demonstrate a
      fundamental understanding of end-of-life issues in order to employ the versatile,
      multidisciplinary approach required to provide the highest quality end-of-life
      care for patients and their families.

PMID- 19386135
TI  - Synovial chondromatosis originating from the synovium of the anterior cruciate
      ligament: a case report.
AB  - A case of synovial chondromatosis originating from the synovium of the anterior
      cruciate ligament (ACL) resulting in a mechanical block to knee extension is
      reported. A 36-year-old man complained of a restricted range of left-knee motion
      and pain when walking. Plain roentgenograms showed normal appearance, however,
      magnetic resonance imaging showed intensity changes in the ACL. Arthroscopically,
      numerous small free bodies were observed. Proliferation of synovium and
      cartilaginous tissues were identified around the ACL. There were no significant
      findings in the synovium except around the ACL. The synovium around the ACL was
      resected and free bodies were washed out. This is the first report of synovial
      chondromatosis originating from the synovium of the ACL.

PMID- 19386136
TI  - Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and
      function.
AB  - BACKGROUND: Human S100A12 is a member of the S100 family of EF-hand calcium
      modulated proteins that are associated with many diseases including cancer,
      chronic inflammation and neurological disorders. S100A12 is an important factor
      in host/parasite defenses and in the inflammatory response. Like several other
      S100 proteins, it binds zinc and copper in addition to calcium. Mechanisms of
      zinc regulation have been proposed for a number of S100 proteins e.g. S100B,
      S100A2, S100A7, S100A8/9. The interaction of S100 proteins with their targets is
      strongly dependent on cellular microenvironment. RESULTS: The aim of the study
      was to explore the factors that influence S100A12 oligomerization and target
      interaction. A comprehensive series of biochemical and biophysical experiments
      indicated that changes in the concentration of calcium and zinc led to changes in
      the oligomeric state of S100A12. Surface plasmon resonance confirmed that the
      presence of both calcium and zinc is essential for the interaction of S100A12
      with one of its extracellular targets, RAGE--the Receptor for Advanced Glycation
      End products. By using a single-molecule approach we have shown that the presence
      of zinc in tissue culture medium favors both the oligomerization of exogenous
      S100A12 protein and its interaction with targets on the cell surface. CONCLUSION:
      We have shown that oligomerization and target recognition by S100A12 is regulated
      by both zinc and calcium. Our present work highlighted the potential role of
      calcium-binding S100 proteins in zinc metabolism and, in particular, the role of
      S100A12 in the cross talk between zinc and calcium in cell signaling.

PMID- 19386137
TI  - Focal therapy for prostate cancer: revolution or evolution?
AB  - The face of prostate cancer has been dramatically changed since the late 1980s
      when PSA was introduced as a clinical screening tool. More men are diagnosed with
      small foci of cancers instead of the advanced disease evident prior to PSA
      screening. Treatment options for these smaller tumors consist of expectant
      management, radiation therapy (brachytherapy and external beam radiotherapy) and
      surgery (cryosurgical ablation and radical prostatectomy). In the highly select
      patient, cancer specific survival employing any of these treatment options is
      excellent, however morbidity from these interventions are significant. Thus, the
      idea of treating only the cancer within the prostate and sparing the non
      cancerous tissue in the prostate is quite appealing, yet controversial. Moving
      forward if we are to embrace the focal treatment of prostate cancer we must: be
      able to accurately identify index lesions within the prostate, image cancers
      within the prostate and methodically study the litany of focal therapeutic
      options available.

PMID- 19386138
TI  - Optimization and validation of multi-coloured capillary electrophoresis for
      genotyping of Plasmodium falciparum merozoite surface proteins (msp1 and 2).
AB  - BACKGROUND: Genotyping of Plasmodium falciparum based on PCR amplification of the
      polymorphic genes encoding the merozoite surface proteins 1 and 2 (msp1 and msp2)
      is well established in the field of malaria research to determine the number and
      types of concurrent clones in an infection. Genotyping is regarded essential in
      anti-malarial drug trials to define treatment outcome, by distinguishing
      recrudescent parasites from new infections. Because of the limitations in
      specificity and resolution of gel electrophoresis used for fragment analysis in
      most genotyping assays it became necessary to improve the methodology. An
      alternative technique for fragment analysis is capillary electrophoresis (CE)
      performed using automated DNA sequencers. Here, one of the most widely-used
      protocols for genotyping of P. falciparum msp1 and msp2 has been adapted to the
      CE technique. The protocol and optimization process as well as the potentials and
      limitations of the technique in molecular epidemiology studies and anti-malarial
      drug trials are reported. METHODS: The original genotyping assay was adapted by
      fluorescent labeling of the msp1 and msp2 allelic type specific primers in the
      nested PCR and analysis of the final PCR products in a DNA sequencer. A
      substantial optimization of the fluorescent assay was performed. The CE method
      was validated using known mixtures of laboratory lines and field samples from
      Ghana and Tanzania, and compared to the original PCR assay with gel
      electrophoresis. RESULTS: The CE-based method showed high precision and
      reproducibility in determining fragment size (< 1 bp). More genotypes were
      detected in mixtures of laboratory lines and blood samples from malaria infected
      children, compared to gel electrophoresis. The capacity to distinguish
      recrudescent parasites from new infections in an anti-malarial drug trial was
      similar by both methods, resulting in the same outcome classification, however
      with more precise determination by CE. CONCLUSION: The improved resolution and
      reproducibility of CE in fragment sizing allows for comparison of alleles between
      separate runs and determination of allele frequencies in a population. The more
      detailed characterization of individual msp1 and msp2 genotypes may contribute to
      improved assessments in anti-malarial drug trials and to a further understanding
      of the molecular epidemiology of these polymorphic P. falciparum antigens.

PMID- 19386140
TI  - Cervico-isthmic corporeal pregnancy with delivery at term: a review of the
      literature with a case report.
AB  - BACKGROUND: True primary cervical pregnancies are rare. Although these can cause
      massive hemorrhage, most of these abort during the first trimester without having
      been diagnosed. However, cervico-isthmic and cervico-isthmic corporeal
      pregnancies are more likely to persist to an advanced gestation in the second and
      third trimester and cause profuse bleeding with attempted removal of the
      placenta. CASE PRESENTATION: A case of cervico-isthmic corporeal pregnancy at
      term with near exsanguinating hemorrhage is reported. A 35-year-old Sri Lankan
      woman presented for prenatal care with the complaint of daily, painless vaginal
      bleeding. An ultrasound showed a cervical pregnancy. Despite counseling regarding
      the poor outcome of cervical pregnancies, the patient wished to continue the
      pregnancy. At repeat cesarean section, bleeding was profuse requiring pressure,
      electrocautery, and oversewing the uterus. The patient developed massive bleeding
      in the recovery room, requiring laparotomy, and total abdominal hysterectomy to
      control bleeding. She received multiple blood transfusions and required re
      exploration for recurrent hemorrhage. The pathology report revealed a placenta
      accreta and chorionic villi at the junction of the isthmus and cervix. After a
      long hospital course, the patient was discharged. CONCLUSION: Cervical
      pregnancies involving the isthmus and isthmus and corpus are more common than
      true cervical pregnancies. They are significant because placental involvement of
      the cervix can cause erosion of the uterine arteries and massive bleeding when
      placental removal is attempted. Anticipatory planning, including permission for
      hysterectomy if necessary, may lead to improved maternal and fetal morbidity.
      TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING
      OBJECTIVES: After completion of this article, the reader should be able to
      distinguish the different types of cervical pregnancies, describe management
      strategies for cervical pregnancies, and summarize the diagnostic criteria for
      cervical pregnancies.

PMID- 19386139
TI  - Peritoneal inclusion cysts: a review.
AB  - OBJECTIVE: To provide a comprehensive review of peritoneal inclusion cysts in the
      female patient population. To define the optimal diagnostic modalities and review
      the medical and surgical options for management, enabling the gynecologist to
      individualize treatment for patients. DATA SOURCES: We searched the MEDLINE
      database for articles with keywords "peritoneal inclusion cyst" and "benign
      (multicystic) mesothelioma." Our search was limited to the English language. All
      reports included a tissue-confirmed diagnosis, except 1. Case reports and case
      series with adolescent and adult patients were reviewed. METHOD OF STUDY: We
      evaluated all studies meeting our criteria for clinical features, histologic
      criteria for diagnosis, imaging and laboratory studies, and treatment modalities.
      TABULATION, INTEGRATION, AND RESULTS: Fifty-two descriptive studies and 1
      prospective cohort study meet criteria for review. Eleven articles focused on
      imaging modalities. Nineteen articles depicted histopathology. Eight addressed
      treatment modalities. CONCLUSION: This is a comprehensive review of peritoneal
      inclusion cysts. We specifically focus on the method of diagnosis and management.
      There is no standard algorithm by which the patients are evaluated, treated, or
      followed up. Peritoneal inclusion cysts have minimal mortality but high
      morbidity. Diagnosis is made by clinical history, ultrasound imaging, and CA-125
      correlation. Magnetic resonance imaging is useful if ultrasound is unclear.
      Tissue sample is necessary for definitive diagnosis. Prior studies have suggested
      that cure is only accomplished with surgical resection; however, patients have a
      50% risk of recurrence. We suggest that the goal for such a chronic disease
      should not be cure, but symptomatic relief through individualization of
      treatment. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians.
      LEARNING OBJECTIVES: After completion of this article, the reader should be able
      to summarize imaging characteristics of peritoneal inclusion cysts, explain the
      epidemiology and risk factors for the development of peritoneal inclusion cysts,
      and describe possible treatment options for peritoneal inclusion cysts.

PMID- 19386141
TI  - The HPV vaccines--which to prefer?
AB  - This review presents an unbiased comparison between the two vaccines available
      against human papillomavirus (HPV). We conducted a PUBMED and Google search for
      the years 1998 to October 2008 using the terms: cervical cancer vaccine, HPV
      vaccine, Gardasil, and Cervarix; and also reviewed abstracts from international
      meetings. Both vaccines are intended to protect against cervical cancer and high
      grade CIN caused by HPV 16 and HPV 18. Only the quadrivalent vaccine is designed
      to prevent condylomata acuminata and low-grade CIN caused by HPV 6 and HPV 11. It
      has been approved by the FDA for women aged 9 to 26 years against vulvar and
      vaginal cancer, and against cervical cancer and precancer. The adjuvant of the
      bivalent vaccine more significantly accelerates an immune reaction. Both vaccines
      demonstrate cross-protection, although against different HPV types. The bivalent
      vaccine is registered for above age 26 in Australia and Israel, and the
      quadrivalent vaccine in the Philippines and Ecuador. Time will verify claims and
      reveal differences. In the meantime, both vaccines are safe and effective for
      their approved indications and, recommendations should be based on individual
      patient characteristics. TARGET AUDIENCE: Obstetricians & Gynecologists, Family
      Physicians. LEARNING OBJECTIVES: After completion of this article, the reader
      should be able to describe the viral targets of the two HPV vaccines, explain the
      potential benefits of HPV vaccination to patients, and compare the data regarding
      the two HPV vaccines.

PMID- 19386142
TI  - From the editor.

PMID- 19386143
TI  - Chronic fatigue in Gulf War veterans: should it be treated as chronic fatigue
      syndrome?

PMID- 19386144
TI  - How we know our own minds: the relationship between mindreading and
      metacognition.
AB  - Four different accounts of the relationship between third-person mindreading and
      first-person metacognition are compared and evaluated. While three of them
      endorse the existence of introspection for propositional attitudes, the fourth
      (defended here) claims that our knowledge of our own attitudes results from
      turning our mindreading capacities upon ourselves. Section 1 of this target
      article introduces the four accounts. Section 2 develops the "mindreading is
      prior" model in more detail, showing how it predicts introspection for perceptual
      and quasi-perceptual (e.g., imagistic) mental events while claiming that
      metacognitive access to our own attitudes always results from swift unconscious
      self-interpretation. This section also considers the model's relationship to the
      expression of attitudes in speech. Section 3 argues that the commonsense belief
      in the existence of introspection should be given no weight. Section 4 argues
      briefly that data from childhood development are of no help in resolving this
      debate. Section 5 considers the evolutionary claims to which the different
      accounts are committed, and argues that the three introspective views make
      predictions that are not borne out by the data. Section 6 examines the extensive
      evidence that people often confabulate when self-attributing attitudes. Section 7
      considers "two systems" accounts of human thinking and reasoning, arguing that
      although there are introspectable events within System 2, there are no
      introspectable attitudes. Section 8 examines alleged evidence of "unsymbolized
      thinking". Section 9 considers the claim that schizophrenia exhibits a
      dissociation between mindreading and metacognition. Finally, section 10 evaluates
      the claim that autism presents a dissociation in the opposite direction, of
      metacognition without mindreading.

PMID- 19386174
TI  - The propositional nature of human associative learning.
AB  - The past 50 years have seen an accumulation of evidence suggesting that
      associative learning depends on high-level cognitive processes that give rise to
      propositional knowledge. Yet, many learning theorists maintain a belief in a
      learning mechanism in which links between mental representations are formed
      automatically. We characterize and highlight the differences between the
      propositional and link approaches, and review the relevant empirical evidence. We
      conclude that learning is the consequence of propositional reasoning processes
      that cooperate with the unconscious processes involved in memory retrieval and
      perception. We argue that this new conceptual framework allows many of the
      important recent advances in associative learning research to be retained, but
      recast in a model that provides a firmer foundation for both immediate
      application and future research.

PMID- 19386209
TI  - Oral lichen planus: a retrospective comparative study between Thai and Croatian
      patients.
AB  - Oral lichen planus (OLP) is a common oral mucosal disease that affects middle age
      patients. However, there are few reports about the incidence of OLP in different
      ethnic groups. The purpose of this study was to compare the characteristics of
      OLP in Thai and Croatian patients. Retrospective data were taken from medical
      records of 175 patients referred to the Oral Medicine Department of Chulalongkorn
      University and 175 patients referred to the School of Dental Medicine, University
      of Zagreb during the 1997-2007 period. In all patients the diagnosis of OLP was
      clinically and histopathologically confirmed. In Thai and Croatian OLP patients,
      females were predominant (the female to male ratio was 3.5:1). Croatian OLP
      patients were older with a significant age difference between female Thai and
      Croatian OLP patients (p<0.05). Atrophic-erosive type of OLP was common in Thai
      patients, whereas reticular OLP was predominant in Croatians (p<0.001). Burning
      sensation was the most common chief complaint in both ethnic groups. Significant
      differences between the two ethnic groups were found in the sites of OLP lesions
      as well as in the occurrence of pain, roughness and white patches, systemic
      diseases and use of medication (p<0.05). Croatian patients had more systemic
      diseases and took more medications than Thai. Three cases showed dysplasia in
      either group, whereas only one Thai patient developed squamous cell carcinoma.
      Although Thai and Croatian patients differed significantly according to the
      clinical type of OLP, the rate of malignant transformation was very low.

PMID- 19386210
TI  - Erythema multiforme with reference to atypical presentation in an HIV-positive
      patient following antiretroviral therapy discontinuation.
AB  - Erythema multiforme (EM) is a skin disease caused by numerous potential
      triggering agents. It is characterized by symmetrically distributed, round,
      erythematous iris lesions, with remarkable tendency of recurrence. The purpose of
      this randomized retrospective study was to summarize our experience concerning
      the etiology, clinical variants and management of EM. We present 12 EM patients,
      along with laboratory, clinical and histopathologic analysis, and an overview of
      the treatment used. According to clinical presentation and histopathologic
      analysis, there were six cases of EM major, five cases of EM minor and one case
      of Stevens-Johnson syndrome. In five patients, EM was associated with the use of
      certain drugs (terbinafine, azithromycin, diclofenac, piroxicam). In three
      patients, the disease was triggered by the herpes simplex virus infection. In
      four cases, the etiologic factor (involved in the occurrence) of EM remained
      unknown. We also present an unusual case of an HIV-positive patient with multiple
      acral target lesions without mucosal involvement, which developed upon
      antiretroviral therapy discontinuation. To our knowledge, no case of such EM
      occurrence has yet been reported. There are various etiologic factors and
      numerous clinical presentations of EM, including acral target lesions and
      atypical widely distributed cutaneous and mucosal lesions.

PMID- 19386211
TI  - Morphological evidence of periodical exacerbation of hyperkeratosis lenticularis
      perstans.
AB  - We present a case of hyperkeratosis lenticularis perstans (Flegel's disease) in a
      71-year-old-woman. Apart from all the typical morphological features of the
      disease, we evidenced mounds of parakeratosis that contained neutrophils,
      alternating with other strata of the horny layers in which no infiltrate was
      seen. Such a pattern has been described in association with diseases that show a
      periodic clinical pattern of presentation with periods of exacerbations and
      remissions. Our case also showed a lichenoid inflammatory chronic infiltrate with
      vacuolation of the basal layer and mild spongiosis. Both findings strongly
      support the hypothesis that the inflammatory infiltrate might play a primary
      role, and that the hyperkeratosis might be a secondary event.

PMID- 19386212
TI  - Treatment of massive rhinophyma by combined electrosurgery and CO2 laser.
AB  - A case of massive rhinophyma that produced significant functional and cosmetic
      difficulties was treated using electrosurgery and carbon dioxide laser. Minimal
      bleeding occurred during the operative procedure despite grotesque enlargement
      and high degree of vascularity of the skin and soft tissue. Using this technique,
      restoration of normal function and excellent cosmetic effect was achieved without
      any complication.

PMID- 19386213
TI  - The basis of topical superoxide dismutase antipruritic activity.
AB  - In humans, as in all mammals and most chordates, three forms of superoxide
      dismutase (SOD) are present: SOD1 is located in the cytoplasm, SOD2 in the
      mitochondria, and SOD3 is extracellular. SOD is used in cosmetic products to
      reduce free radical damage to the skin, for example, to reduce fibrosis following
      radiation for breast cancer. Pruritus is one of the most common symptoms of skin
      diseases, but can also be a major symptom of systemic diseases (e.g., malignancy,
      infection or metabolic disorders). There are various antihistaminics used as
      antipruritogenic substances. In the genesis of pruritus there are many
      pruritogens involved, not only histamine and leukotrienes such as acetylcholine,
      cytokines, kallikreins, proteases, kinins, opioids, etc., which are described. On
      many occasions, we observed that topical SOD seemed to possess strong
      antipruritic activity, even in anti-histamine-resistant pruritus. We analyzed
      literature data on the effect of SOD as an anti-pruritogen on NK-1 receptors and
      proinflammatory cytokines, its regulatory role in calcitonin gene-related peptide
      production and expression, down-regulation of TNF- and numerous cytokines, and
      suppression of nitric oxide production.

PMID- 19386214
TI  - Dermatologic medication in pregnancy.
AB  - In female body, a vast number of skin changes occur during pregnancy. Some of
      them are quite distressing to many women. Therefore, performing treatment for
      physiologic skin changes during pregnancy with antiinfective agents,
      glucocorticosteroids, topical immunomodulators, retinoids, minoxidil, etc., is
      discussed. Drug administration during pregnancy must be reasonable.

PMID- 19386215
TI  - An overview of the cosmetic treatment of facial muscles with a new botulinum
      toxin.
AB  - Botulinum toxin (BTX) is used nowadays in a much more differentiated way with a
      much more individualized approach to the cosmetic treatment of patients. To the
      well known areas of the upper face new indications in the mid and lower face have
      been added. Microinjection techniques are increasingly used besides the classic
      intramuscular injection technique. BTX injections of the mid and lower face
      require small and smallest dosages. The perioral muscles act in concert to
      achieve the extraordinarily complex movements that control facial expressions,
      eating, and speech. As the mouth has horizontal as well as vertical movements,
      paralysis of these perioral muscles has a greater effect on facial function and
      appearance than does paralysis of muscles of the upper face, which move primarily
      in vertical direction. It is essential that BTX injections should achieve the
      desired cosmetic result with the minimum dose without any functional discomfort.
      In this paper the three-year clinical experience with average dosages for an
      optimal outcome in the treatment of facial muscles with a newly developed
      botulinum toxin type A (Xeomin) free from complexing proteins is presented.

PMID- 19386216
TI  - Nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs, angiotensin
      converting enzyme inhibitors, radiocontrast media, local anesthetics, volume
      substitutes and medications used in general anesthesia.
AB  - Urticaria and angioedema are common allergic manifestations and medications are
      one of common triggering factors. The most severe immediate drug reaction is
      anaphylaxis. Apart from the well established IgE-mediated immediate type
      hypersensitivity reactions, the pathogenesis of drug-induced urticaria,
      angioedema and anaphylaxis often remains obscure. In this article, emphasis is
      put on nonallergic reactions to the most commonly used drug groups of
      nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors,
      radiocontrast media, volume expanders and drugs used in general anesthesia.
      Urticaria is the second most common drug eruption after maculopapular exanthema.
      The mechanisms of acute urticarial reactions are multiple, mostly IgE mediated,
      but some drugs can induce immune complex reactions and activate complement
      cascade, while others can induce direct activation of mast cells and
      degranulation or activation of complement by non-immune mechanisms. With
      different types of medications different pathomechanisms are involved. Non
      steroid anti-inflammatory drugs are thought to cause reaction due to
      cyclooxygenase-1 inhibition and overproduction of leukotrienes, blamed for
      cutaneous and respiratory symptoms. Angiotensin-converting enzyme inhibitors can
      cause fatal angioedema, which is partially explained with bradykinin excess and
      impairment of aminopeptidase P and dipeptidyl peptidase IV that are involved in
      the metabolism of substance P and bradykinin. It remains unknown what additional
      mechanisms are involved. Radiocontrast media and local anesthetics mostly cause
      nonallergic hypersensitivity reaction, but in rare cases true allergic reaction
      can occur. Dextran is known to cause IgG mediated, immune complex anaphylaxis and
      it is recommended to use human serum albumin as the safest colloid.

PMID- 19386217
TI  - Allergic contact dermatitis to antibacterial agents.
AB  - Topical antibiotics are frequently introduced in therapy by various specialists,
      e.g., dermatologists-venereologists, ENT specialists, proctologists,
      ophthalmologists, and others. In dermatology, topical antibiotics are used in the
      treatment of superficial inflammatory skin lesions, acne and rosacea. These
      agents are also used in the prevention of inflammatory lesions after surgical and
      corrective procedures. Long-term and uncontrolled application of topical
      antibiotics, on the skin with impaired protective barrier in particular, implies
      a risk for the development of hypersensitivity to these agents. Considering the
      very wide utilization of these agents, hypersensitivity to topical antibiotics
      poses a major problem worldwide. The groups at a high risk of contact sensitivity
      to topical antibiotics include patients with chronic venous insufficiency,
      chronic ulcers and chronic otitis externa, as well as individuals at occupational
      exposure to antibiotics, e.g., human medicine and veterinary medicine
      professionals, pharmaceutical industry workers, cattle breeders, etc. When long
      term therapy fails to result in improvement in the above mentioned chronic
      states, the possibility of allergic reactions to topical agents should be taken
      in consideration. Cross-sensitivity, which is frequently associated with the use
      of topical aminoglycoside antibiotics, poses a significant problem.

PMID- 19386218
TI  - Anaphylactic shock caused by a cosmetic cream applied fourteen hours before
      manifested on medical examination: case report.

PMID- 19386219
TI  - Human dirofiliariasis in Croatia.
AB  - Dear Editor, I read with great interest the article "Subcutaneous dirofilariasis
      caused by Dirofilaria repens diagnosed by histopathologic and polymerase chain
      reaction analysis", published in the last issue of Acta Dermatovenerologica
      Croatica. The authors of the article describe a case of human dirofilariasis with
      typical subcutaneous presentation of the parasite. They cite this case as the
      fourth reported case of the disease in Croatia (1). However, dirofilariasis in
      Croatia has been reported more frequently than it looks at the first glance. The
      main reason for this discrepancy is that some cases have been reported in
      journals and other publications with poor or no visibility. The first case
      reported was the case of conjunctival dirofilariasis described by Bujger et al.
      in 1996, published in Ophthalmologia Croatica. Unaware of this case, due to its
      invisibility in the main journal databases, in 2003 Puizina-Ivic et al. reported
      two cases of the disease as the first cases of human dirofilariasis in Croatia.
      Actually, these were the first reported cases of the subcutaneous form of the
      disease in our country, followed by the case presented as subcutaneous mammary
      nodule (3,4). All of these subcutaneous cases were from the southern part of
      Croatia, where additional cases were frequently encountered and reported (5,6).
      In 2007, another case of ocular dirofilariasis was reported, followed by two
      reported cases of the subcutaneous form of the disease, all from the inland part
      of Croatia (7,8). In all of the reported cases, Dirofilaria repens was identified
      as the causative agent. Altogether, including the case reported in your journal,
      at least 10 human cases of this emerging zoonosis have been reported in Croatia
      so far, confirming the conclusion by Marusic et al. that Croatia represents an
      endemic area, like other countries in the Mediterranean basin (1). As the
      majority of cases presented as subcutaneous nodules, dermatologists and
      dermatopathologists should familiarize themselves with the clinical and
      histologic aspects of the disease, considering it in the differential diagnosis
      of solitary nodules in subcutaneous tissue.

PMID- 19386220
TI  - Corrective dermatology: yesterday - today - tomorrow.

PMID- 19386225
TI  - Utility and evaluation of new variable-number tandem-repeat systems for
      genotyping mycobacterial tuberculosis isolates.
AB  - We compared mycobacterial interspersed repetitive unit (MIRU)-variable number
      tandem repeat (VNTR) typing to traditional spoligotyping for discriminating
      Mycobacterium tuberculosis (MTB) strains. Our 17-loci MIRU-VNTR typing method was
      found to be superior to spoligotyping for non-Beijing family strains. To extend
      the method we also established PCR-based rapid genotyping protocols for Beijing,
      East-African-Indian and U lineages.

PMID- 19386226
TI  - New strategies for electrophoresis analysis of enterobacterial repetitive
      intergenic consensus PCR in animal intestinal microflora.
AB  - Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) is a molecular
      biological technology that can be used to study microbial community diversity and
      dynamics. In many reports, investigations of microbial diversity from
      environmental samples were based on the agarose gel electrophoresis (AGE)
      patterns of ERIC-PCR amplified products. This is not a sound practice, since
      bands with identical positions can contain different sequences; thus, this
      practice could possibly exaggerate the similarities or diversities among samples.
      To mitigate this issue, we employed a denaturing gradient gel electrophoresis
      (DGGE) strategy to explore DNA bands with the same size, between ERIC-PCR
      profiles of samples. DPS software was used with Shannon-Wiener diversity index
      (H') to analyze ERIC-PCR fingerprint profiles. H' revealed that the microbial
      community diversity at DGGE was higher than with AGE. The results of this study
      suggest that the ERIC-PCR assays with DGGE can provide a better assessment of
      electrophoresis pattern with regards to the structure of an intestinal microbial
      community.

PMID- 19386227
TI  - A bovine macrophage screening system for identifying attenuated transposon
      mutants of Mycobacterium avium subsp. paratuberculosis with vaccine potential.
AB  - Johne's disease is a chronic granulomatous enteritis in ruminants caused by
      Mycobacterium avium subsp. paratuberculosis (MAP). The disease is responsible for
      considerable economic losses in the livestock industry and in particular within
      the dairy sector. A more effective vaccine against Johne's disease would be of
      major benefit. In this study, we developed an efficient procedure for identifying
      mutants of MAP with reduced virulence that are potential live vaccine candidates
      against Johne's disease. A mariner transposon was used to create random
      insertional libraries in two different MAP strains (989 and k10), an effective
      cattle macrophage survival system was developed, and a total of 1890 insertion
      mutants were screened by using a 96-prong multi-blot replicator (frogger) system.
      Two of the transposon mutants with poor survival ability in macrophages were
      tested in mice. These strains were found to be attenuated in vivo, thereby
      validating the further use of this macrophage screening system to identify MAP
      mutants with potential as candidate vaccines against Johne's disease.

PMID- 19386228
TI  - p66(ShcA) adaptor molecule accelerates ES cell neural induction.
AB  - SHC genes codify for a family of adaptor molecules comprising four genes.
      Previous data have implicated the Shc(s) molecules in stem cell division and
      differentiation. Specifically, the p66(ShcA) isoform has been found to contribute
      to longevity and resistance from oxidative stress. Here we report that p66(ShcA)
      is up-regulated during in vitro neural induction in embryonic stem cells.
      p66(ShcA) over-expression in ES cells reduces GSK-3beta kinase activation and
      increases beta-catenin stabilization and its transcriptional activity. p66(ShcA)
      over-expression results in ES cells undergoing an anticipated neural induction
      and accelerated neuronal differentiation. Similar effects are obtained in human
      ES cells over-expressing p66(ShcA). This study reveals a role for p66(ShcA) in
      the modulation of Wnt/beta-catenin pathway and in ES cell neuralization which is
      consistent between mouse and human.

PMID- 19386229
TI  - Low molecular weight Abeta induces collapse of endoplasmic reticulum.
AB  - The endoplasmic reticulum (ER) is a dynamic multifunction organelle that is
      responsible for Ca(2+) homeostasis, protein folding, post-translational
      modification, protein degradation, and transportation of nascent proteins.
      Disruption of ER architecture might affect the normal physiology of the cell. In
      yeast, expansion of the ER is observed under unfolded protein response (UPR) and
      subsequently induces autophagy initiated from the ER. Here, we found that soluble
      low molecular weight of Abeta disrupted the anchoring between ER and microtubules
      (MT) and induced collapse of ER. In addition, it decreased the stability of MT.
      Subsequently, low molecular weight Abeta triggered autophagy and enhanced
      lysosomal degradation, as shown by electron microscopy and live-cell imaging.
      Dysfunction of ER can be further proved in postmortem AD brain and transgenic
      mice bearing APP Swedish mutation by immunohistochemical analysis of
      calreticulin. Treatment with Taxol, a MT-stabilizing agent, could partially
      inhibit collapse of the ER and induction of autophagy. The results show that
      Abeta-induced disruption of MT can affect the architecture of the ER.
      Collapse/aggregation of the ER may play an important role in Abeta peptide
      triggered neurodegenerative processes.

PMID- 19386231
TI  - Cell autonomous defects in cortical development revealed by two-color chimera
      analysis.
AB  - A complex program of cell intrinsic and extrinsic signals guide cortical
      development. Although genetic studies in mice have uncovered roles for numerous
      genes and gene families in multiple aspects of corticogenesis, determining their
      cell autonomous functions is often complicated by pleiotropic defects. Here we
      describe a novel lentiviral-based method to analyze cell autonomy by generating
      two-color chimeric mouse embryos. Ena/VASP-deficient mutant and control embryonic
      stem (ES) cells were labeled with different fluorescent chimeric proteins (EGFP
      and mCherry) that were modified to bind to the plasma membrane. These labeled ES
      cells were used to generate two-color chimeric embryos possessing two genetically
      distinct populations of cortical cells, permitting multiple aspects of neuronal
      morphogenesis to be analyzed and compared between the two cell populations. We
      observed little difference between the ability of control and Ena/VASP-deficient
      cells to contribute to cortical organization during development. In contrast, we
      observed axon fiber tracts originating from control neurons but not Ena/VASP
      deficient neurons, indicating that loss of Ena/VASP causes a cell autonomous
      defect in cortical axon formation. This technique could be applied to determine
      other cell autonomous functions in different stages of cortical development.

PMID- 19386232
TI  - Nogo-A inhibits necdin-accelerated neurite outgrowth by retaining necdin in the
      cytoplasm.
AB  - Nogo-A has been identified in the central nervous system as an inhibitor for
      axonal regeneration. Previous works have mainly focused on Nogo-A in
      oligodendrocytes and the roles of neuronal intracellular Nogo-A remain elusive.
      To gain deep insight into the physiological functions of Nogo-A, a yeast two
      hybrid screening was performed with Nogo-66 as bait. We identified a new
      interaction between Nogo-66 and necdin. Mutagenesis analysis revealed that the
      central region of necdin was indispensable for the interaction of necdin with
      Nogo-66. The interaction was further confirmed by co-immunoprecipitation in
      neural tissues and cultured cortical neurons. Morphological evidence showed that
      Nogo-A and necdin highly colocalized in rat cortical and dorsal root ganglia
      neurons. Ectopic expression of Nogo-A in HEK293 cells led to retention of necdin
      from the nucleus to the cytoplasm. Furthermore, overexpression of Nogo-A in PC12
      cells and cultured cortical neurons inhibited necdin-accelerated neurite
      outgrowth. Meanwhile, necdin was found to be significantly sequestered in the
      cytoplasm of PC12 cells stably overexpressing Nogo-A. Together, these data
      suggest that Nogo-A is a novel necdin binding protein and inhibits necdin
      accelerated neuronal neurite outgrowth by sequestering necdin in the cytoplasm.

PMID- 19386233
TI  - PF9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine] confers MAO-B
      independent neuroprotection in ER stress-induced cell death.
AB  - Endoplasmic reticulum (ER) stress has recently been proposed as one of the
      factors contributing to apoptotic cell death in Parkinson's disease (PD).
      Although MAO-B inhibitors have been suggested to exert neuroprotective effects in
      several experimental models of PD, their effectiveness against ER stress has not
      been fully determined. Therefore, we have studied the potential usefulness of
      PF9601N, a non-amphetamine-like MAO-B inhibitor, in preventing cell death in a
      cell culture model of ER stress. Exposure of human dopaminergic cell line SH-SY5Y
      to the ER stressor brefeldin A led to Golgi disassembly, activation of the
      unfolded protein response (UPR), and subsequent expression of the proapoptotic
      mediator GADD153/CHOP. In this context, PF9601N pretreatment prevented brefeldin
      A-induced UPR responses, thus blocking the expression of GADD153/CHOP and
      resulting apoptotic features. In summary, our data suggests that PF9601N is able
      to block the responses elicited by ER stress, thus preventing apoptotic cell
      death in brefeldin A-treated cells.

PMID- 19386237
TI  - Enhanced degradation of synaptophysin by the proteasome in mucopolysaccharidosis
      type IIIB.
AB  - The interruption of the lysosomal degradation of heparan sulfate oligosaccharides
      has deleterious consequences on the central nervous system in children or in
      animals with mucopolysaccharidosis type III (Sanfilippo syndrome). Behavioural
      manifestations are prominent at disease onset, suggesting possible early synaptic
      defects in cortical neurons. We report that synaptophysin, the most abundant
      protein of the synaptic vesicle membrane, was detected at low levels in the
      rostral cortex of MPSIII type B mice as early as 10 days after birth. This defect
      preceded other disease manifestations, was associated with normal neuron and
      synapse density and corrected after gene transfer inducing re-expression of the
      missing lysosomal enzyme. Clearance of heparan sulfate oligosaccharides in
      cultured embryonic MPSIIIB cortical neurons or treatment with proteasome
      inhibitors restored normal synaptophysin levels indicating that heparan sulfate
      oligosaccharides activate the degradation of synaptophysin by the proteasome with
      consequences on synaptic vesicle components that are relevant to clinical
      manifestations.

PMID- 19386238
TI  - Environmental toxicity, oxidative stress, human disease and the "black box" of
      their synergism: how much have we revealed?

PMID- 19386239
TI  - Cytogenetic biomonitoring of Brazilian workers exposed to pesticides:
      micronucleus analysis in buccal epithelial cells of soybean growers.
AB  - Pesticides have been considered potential chemical mutagens and various
      agrochemical ingredients possess mutagenic properties. Biomonitoring provides a
      useful tool to estimate the genetic risk from exposure to a complex mixture of
      chemicals. In general genetic damage associated with pesticides occurs in human
      populations subject to high exposure levels due to intensive use, misuse or
      failure of control measures. Few studies have been carried out using the
      micronucleus (MN) analysis in buccal cells of farm workers and, from the
      available data, only one has found a positive relationship. Micronuclei were
      analyzed in 29 Brazilian workers exposed to pesticides in soybean fields and in
      37 non-exposed individuals. The results obtained indicate that the mean number of
      cells with MN in the exposed group (3.55+/-2.13) was significantly higher than in
      the control group (1.78+/-1.23). The number of cells with MN was not influenced
      by age, smoking habit, smoking time, number of cigarettes/day, alcohol
      consumption and years of exposure to pesticides. The genotoxic potential of the
      pesticides used in soybean fields may explain the detectable increase of cells
      with MN in exposed workers.

PMID- 19386240
TI  - Performance of the comet assay in a high-throughput version.
AB  - The high-throughput comet assay was developed to reduce the processing time and
      to increase sample-throughput of the assay as described by Tice et al. (RR. Tice,
      E. Agurell, D. Anderson, B. Burlinson, A. Hartmann, H. Kobayashi, Y. Miyamae, E.
      Rojas, JC. Ryu, YF. Sasaki. Single cell gel/comet assay: guidelines for in vitro
      and in vivo genetic toxicology testing, Environ. Mol. Mutagen.35 (2000) 206-221).
      This high-throughput version allows for the processing of up to 400 samples per
      day. The basis of the new assay is a 96-well plate (multichamber plate, MCP)
      suitable for electrophoresis. After exposure of the cells to genotoxic agents,
      the walls of the MCP are separated from the bottom plate. All 96 samples together
      then go through lysis, alkaline unwinding, electrophoresis, neutralization, and
      staining. In this study, the first concentration-dependent results obtained with
      the high-throughput version are shown and a comparison is made with the standard
      version of the comet assay using five representative chemicals with different
      genotoxic properties. These genotoxic chemicals are methyl methanesulfonate (MMS)
      and ethylnitrosourea, which form small alkylation adducts, 4-nitroquinoline-1
      oxide for bulky adducts, cisplatin for DNA cross-links, and H(2)O(2) for direct
      DNA breakage. For medium and high effective concentrations a standard deviation
      of 3-20% for three replicates (25 comets per sample) was determined. A comparison
      of the standard assay with the high-throughput version revealed similar results
      for MMS and H(2)O(2). The integrated viability assay (FDA assay), which was
      performed after chemical treatment and before detachment of the bottom from the
      walls of the MCP, did not influence the outcome of the comet formation. In
      conclusion, the high-throughput version of the comet assay facilitates the
      determination of genotoxicity in cases where large numbers of samples have to be
      measured, such as during testing of industrial chemicals, biomonitoring of
      environmental samples, and early screening of drug candidates for
      genotoxicity/photogenotoxicity. For such applications the cost- and time-saving
      of the high-throughput method provides substantial advantages over the standard
      comet assay.

PMID- 19386241
TI  - Inhibition of mitomycin C-induced chromosomal aberrations by micrometer powder of
      selenium-enriched green tea in mice spermatocytes.
AB  - The anticlastogenic effect of micrometer powder of selenium-enriched green tea
      (MSTP) was evaluated by using a chromosomal aberration assay in mouse testicular
      cells. Animals fed with a Se-deficient diet were treated with MSTP, micrometer
      powder of regular green tea (MRTP), selenite, and MRTP + selenite for 30 days by
      an intragastric route, followed by treatment of mitomycin C (MMC) on day 19
      through intraperitoneal injection (ip). Selenium status and antioxidant enzymes
      were measured. Results indicated that MSTP showed a significant capability to
      reduce the incidence of MMC-induced chromosomal aberrations in spermatocytes from
      22.7% to 6.7%. This inhibitory was highest, for MSTP, at 73.1%, while it was only
      38.4% for MRTP. After 30 days of a Se-deficient diet, mice, either with or
      without the MMC treatment, showed a lower selenium concentration in blood and
      liver as well as lower enzyme activity of the antioxidants, GPx and SOD.
      Supplementation with MSTP, selenite, or selenite + MRTP enhanced the activities
      of these antioxidant enzymes. This enhancement was accompanied with a concomitant
      elevation of selenium levels, which favored the synthesis of the seleno-enzyme
      GPx and protected the cells from the MMC-induced oxidative stress. Our results
      indicate that MSTP is both able to prevent the chromosomal aberrations induced by
      MMC in mouse spermatocytes and to enhance GPx and SOD activity in blood serum and
      liver.

PMID- 19386242
TI  - The introduction of the Salmonella/microsome mutagenicity assay in a groundwater
      monitoring program.
AB  - The objective of this study was to verify the possible inclusion of the
      Salmonella/microsome mutagenicity assay in a groundwater monitoring program as a
      complementary assay to assess water quality. Groundwater samples belonging to
      seven wells from different types of aquifers were analyzed. Three different
      methods for sample preparation were used: membrane filtration; liquid-liquid and
      XAD-4 extraction. The filtered samples were tested using TA98, TA100, YG1041 and
      YG1042 and the water extracts only with TA98 and TA100. No mutagenic activity was
      observed in any of the 16 filtered samples tested. Out of the 10 samples analyzed
      using XAD-4 extraction, five showed mutagenic activity with potency ranging from
      130 to 1500 revertants/L. Concerning the liquid-liquid extraction, from the 11
      samples analyzed, 3 showed mutagenicity. The XAD-4 extraction was the most
      suitable sample preparation. TA98 without S9 was found to be the most sensitive
      testing condition. The wells presenting water samples with mutagenic activity
      belonged to unconfined aquifers, which are more vulnerable to contamination. The
      data suggest that Salmonella/microsome assay can be used as an efficient
      screening tool to monitor groundwater for mutagenic activity.

PMID- 19386243
TI  - Influence of glutathione levels on radiation-induced chromosomal DNA damage and
      repair in human peripheral lymphocytes.
AB  - Endogenous thiols, especially the tripeptide-reduced glutathione (GSH), are known
      to play an important role in cellular defense against radiation. However, there
      are evidences that suggest that GSH may not be an efficient protector of DNA. The
      present study will determine whether modulation of endogenous GSH levels protects
      or potentiates the amount of chromosomal damage induced by ionizing radiation
      (IR). Human lymphocytes were isolated and then treated with GSH (for 1h) or
      buthionine sulfoximine (BSO; GSH-depleting agent for 5 h) before X-irradiation.
      DNA damage was analyzed by scoring chromosome aberrations (CAs) and by comet
      assay. The level of endogenous GSH was measured in lymphocytes treated with GSH,
      BSO or X-rays. A roughly 20% increase in endogenous GSH level was observed after
      a 3-h treatment with exogenous GSH and this reduced the frequency of all types of
      CA and aberrant metaphase chromosomes induced by 1 and 2 Gy of X-rays and also
      decreased the tail moment as determined by comet assay, suggesting radiation
      protection. Such uniform protection by GSH pretreatment was not visible while
      cells were exposed to 3 Gy or higher. Interestingly, in GSH-depleted lymphocytes,
      the frequency of radiation-induced CA was increased in a non-uniform manner.
      Therefore, an increase in the level of endogenous GSH in lymphocytes was unable
      to reduce chromosomal damage induced by 3 Gy or above, whereas decrease in the
      level of GSH enhanced the frequency of CA at all radiation doses in a non-uniform
      manner. It seems that GSH did not act as a radioprotector against DNA damage
      induced by higher dose X-rays rather it acts as a modulator of DNA repair
      activity.

PMID- 19386244
TI  - Evaluation of the cytotoxicity and genotoxicity of curcumin in PC12 cells.
AB  - Neurotoxicity induced by reactive oxygen species can appear as an adverse effect
      of chemotherapy treatment with platinum compounds, such as cisplatin. The use of
      this drug in clinical practice is limited due to its adverse effects, including
      nephrotoxicity, ototoxicity, neurotoxicity and genotoxicity. Functional foods or
      nutraceuticals have demonstrated potential neuroprotective activity in several
      experiments and models. This study aimed to investigate the possible cytotoxicity
      and genotoxicity/antigenotoxic effects of curcumin in PC12 cells exposed to
      cisplatin. Cell viability and genotoxicity/antigenotoxicity were evaluated by the
      MTT assay and micronucleus test, respectively. PC12 cells were treated with
      different concentrations of cisplatin and curcumin (0.5 -- 128 microg/mL).
      Analysis of the results showed that high concentrations of curcumin were
      cytotoxic and increased micronuclei frequency compared to the control group. In
      the associated treatments, at all three concentrations evaluated, curcumin
      significantly reduced the total frequency of micronuclei induced by cisplatin.
      Determining the cytotoxic and genotoxic/antigenotoxic effects of this frequently
      used antioxidant in a neuronal model is important to assess possible hazards when
      combined with other chemical agents, including chemotherapy drugs used in cancer
      therapy.

PMID- 19386245
TI  - Micronuclei frequency in peripheral blood lymphocytes of thyroid cancer patients
      after radioiodine therapy and its relationship with metastasis.
AB  - In most cancers peripheral blood lymphocytes exhibit DNA damage. In the case of
      thyroid cancer the micronucleus (MN) assay has been used to assess DNA damage
      before and after exposure to iodine-131 ((131)I). The aim of our study was to use
      this method to assess DNA damage in peripheral blood lymphocytes of thyroid
      cancer patients and search for its relationship with metastasis as well as (131)I
      exposure. A significant increase in micronuclei frequency was observed in
      peripheral blood lymphocytes of 54 thyroid cancer patients in comparison to 38
      controls (p=0.000). Further analysis revealed significant elevation in
      micronuclei index from 48.5 MN/1000 BN cells (range: 25.1-111.2, n=25) in
      patients without metastasis to 68.1 MN/1000 BN cells (range: 26.2-135.5, n=29,
      p=0.001) in group of patients with metastasis to one or more sites. There was no
      clear correlation between the micronuclei frequency and the therapeutic (131)I
      dose ranging from 0.41 to 31.5 GBq with the exposure interval of <1 to 126
      months. In addition, age and sex did not show any influence on micronuclei
      frequency in either patients or control population. These findings are indicative
      of increased basal DNA damage in thyroid cancer patients before treatment.
      Radioiodine treatment did not increase DNA damage measured by the micronuclei
      frequency for the interval between the last radioiodine dose administered and
      analysis of blood sample. However a significant increase of peripheral blood
      lymphocytes micronuclei was observed in thyroid cancer patients with metastasis.

PMID- 19386246
TI  - Sensitivity of Tradescantia pallida (Rose) Hunt. 'Purpurea' Boom to genotoxicity
      induced by ozone.
AB  - The aims of this study were to investigate the sensitivity of Tradescantia
      pallida 'Purpurea' to genotoxicity induced by ozone, by means of the micronucleus
      (MCN) bioassay, to verify whether the intensity of genotoxic responses in
      inflorescences is modulated by concentrations of ascorbic acid (AA) in their
      bracts, and/or by air temperature variations during the progress of the bioassay,
      and to define the time lag necessary after ozone exposure to observe maximal
      genotoxic effects. Flowering branches were exposed to filtered air (control) and
      to 60 ppb of ozone (ozone) for 3h in fumigation chambers during spring, autumn,
      winter and summer. After exposure, they were maintained for 24-120 h under
      filtered air for recovery. A sub-group of each treatment was taken every 24h,
      when MCN was scored in inflorescences and the levels of AA were determined in
      bracts. Ozone caused a significant increase in the frequency of MCN after 24-120
      of recovery, compared to measurements in inflorescences from the control
      treatment, but maximal MCN rate was reached between 72 and 120 h of recovery. The
      highest percentages of MCN in both fumigation treatments were found during the
      winter experiment. Ozone exposure did not induce significant changes in the
      content of AA. However, it was positively influenced by daily amplitude of air
      temperature during the period of the bioassay. The intensity of genotoxic damage
      and the time lag necessary to visualize an enhanced number of MCN depended on the
      levels of ascorbic acid in bracts 24h before MCN scoring and on the daily
      amplitude of air temperature during the development of the bioassay. Narrower
      ranges between daily maximum and minimum temperatures (around 4 degrees C) during
      the days of experiment seemed to promote a more efficient diagnostic of
      genotoxiciy induced by ozone.

PMID- 19386247
TI  - Genotoxic effects of vehicle traffic pollution as evaluated by micronuclei test
      in tradescantia (Trad-MCN).
AB  - The quality of life in large urban centers is directly affected by the air
      quality there. Atmospheric monitoring is therefore imperative, and bioassays
      using plant models to detect the effects of genotoxic agents are recognized as
      giving excellent results. The present study utilized Trad-MCN to evaluate the
      genotoxic effects of atmospheric pollutants in the city of Feira de Santana,
      Bahia State, Brazil, in three locations with varying traffic loads.
      Inflorescences were collected on a monthly basis from plants growing in these
      locations in both passive and active monitoring regimes. The occurrence of
      micronuclei (MCN) was found to be proportional to vehicular flux under both
      monitoring regimes; with the plants being accompanied by active monitoring
      demonstrating the greatest sensitivity to atmospheric contamination. The results
      indicated that locations with the most intense vehicular traffic demonstrated
      significant atmospheric contamination by pollutants able to damage DNA.

PMID- 19386248
TI  - Genotoxic, cytostatic, antineoplastic and apoptotic effects of newly synthesized
      antitumour steroidal esters.
AB  - In this study, we have investigated the genotoxic, cytostatic, antineoplastic and
      apoptotic effects of three newly synthesized modified steroidal esters, having as
      alkylating agent p-N,N-bis(2-chloroethyl) aminophenyl butyrate (CHL) or p-N,N
      bis(2-chloroethyl) aminophenyl acetate (PHE) esterified with the steroidal
      nucleus modified in the B- and D-ring. The genotoxic and cytotoxic effects of the
      compounds were investigated both in vitro, in lymphocyte cultures obtained from
      blood samples of healthy donors and in vivo, in ascites cells of P388 leukemia
      obtained from the peritoneal cavity of DBA/2 mice. Preparations were scored for
      sister-chromatid exchange (SCE) and proliferation-rate indices (PRI). The newly
      synthesized compounds were also studied for antineoplastic activity against
      lymphocytic P388 and lymphoid L1210 leukemias in mice, by calculating the mean of
      the median survival of the drug-treated animals (T) versus the untreated control
      (C) (T/C%). The activity of caspase-2 and caspase-3, indicators of apoptosis, was
      assessed biochemically in primary cultures of human lymphocytes. Our results show
      that the newly synthesized compounds caused severe genotoxic effects by
      significantly increasing the frequency of SCE and decreasing the PRI values in
      cultures of peripheral lymphocytes in vitro and in ascites cells of lymphocytic
      P388 leukemia in vivo. A significant correlation was also observed in both the in
      vitro and in vivo experiments: the higher the SCE frequency the lower the PRI
      value (r=-0.65, P<0.001 and r=-0.99, P<0.01, respectively). The measured
      antileukemic potency was statistically increased by all test compounds in both
      types of tumours, while the activity of caspase-2 and caspase-3 showed a
      statistically significant increase after two periods of exposure. The genotoxic
      (increase of SCE), cytostatic/cytotoxic (decrease of PRI) and antileukemic
      effects (increase of T/C%) in combination with the induction of apoptosis
      (activation of caspase-2 and caspase-3) caused by the newly synthesized
      compounds, lead us to propose them as agents with potentially antineoplastic
      properties.

PMID- 19386249
TI  - A case-control study on the effect of p53 and p73 gene polymorphisms on gastric
      cancer risk and progression.
AB  - The p53 protein and its functional homologue p73 share several functions in
      modulating cell-cycle control and apoptosis. Based on the functional interaction
      between p53 and p73 in carcinogenesis, we investigated the combined effect of p73
      G4C14-to-A4T14 and p53 gene polymorphisms and their interaction with selected
      environmental factors, on the risk for gastric cancer in a hospital-based case
      control study conducted in Italy. The effect of these polymorphisms on cancer
      progression was also investigated. One hundred and fifteen gastric cancer cases
      and 295 hospital controls were genotyped for p73 G4C14-to-A4T14, and p53 exon 4
      (Arg72Pro), intron 3 and intron 6 polymorphisms. An increased risk for gastric
      cancer was found to be associated with the inheritance of the p73 homozygous
      variant genotype among the gastric cancer intestinal histotype (odds ratio
      (OR)=6.75; 95% confidence interval (95% CI)=1.88-24.24). An effect modification
      of the p73 variant allele by gender was observed [(OR=2.82; 95%CI=1.24-6.40)
      among females, versus an OR of 0.70 (95%CI=0.32-1.54) among males; p-value for
      homogeneity among strata estimates =0.03]. Gene-gene interaction analyses
      demonstrated that individuals with combined p53 exon 4 and intron 6 variant
      alleles are borderline significantly protected from gastric cancer (OR=0.52; 95%
      CI=0.26-1.07; p-value for interaction =0.005), which was confirmed by the
      haplotype analysis. Finally, a poorer survival was observed among carriers of the
      variant allele of p53 intron 6 if compared with those carrying both wild-type
      alleles (p-value for log-rank test =0.02). This study shows that the p73 G4C14-to
      A4T14 polymorphism may be a risk factor for gastric cancer, as reported from
      other studies in different tumour sites among Caucasians. Along with the
      protective effect of p53 exon 4-intron 6 allelic variants, already noted for
      breast and lung cancer, our results require confirmation from larger studies.

PMID- 19386250
TI  - Comparison of sensitivity to arsenic compounds between a Bhas 42 cell
      transformation assay and a BALB/c 3T3 cell transformation assay.
AB  - A short-term cell transformation assay has recently been developed, using Bhas 42
      cells which were established from BALB/c 3T3 cells transfected by v-Ha-ras gene
      and postulated to be initiated in the two-stage carcinogenesis theory. The Bhas
      42 cell transformation assay has been reported to be capable of detecting
      initiating and promoting activities of chemical carcinogens, according to the
      different protocols, initiation assay and promotion assay, respectively. The
      assay is superior to classical transformation assays in cost and labor
      performance. The present study was carried out to compare its sensitivity with
      that of a classical BALB/c 3T3 cell system. We performed the Bhas 42 cell
      transformation assay with inorganic arsenic compounds which are potent
      environmental carcinogens in human but not mutagens in bacteria or weak mutagens
      in mammalian cells in vitro. Sodium arsenite, disodium arsenate, and their
      metabolites, monomethylarsonic acid and dimethylarsinic acid (DMAA) were included
      in the study. Sodium arsenite was positive in the initiation assay and all
      compounds except for DMAA were positive in the promotion assay. These results
      were compared with reported data in a two-stage BALB/c 3T3 cell transformation
      assay. The sensitivity of Bhas 42 cell transformation assay was found to be
      similar to that of the conventional BALB/c 3T3 cell transformation assay for the
      detection of initiating activities of arsenic compounds. For the detection of
      promoting activities, its sensitivity was equivalent to that of the two-stage
      BALB/c 3T3 cell transformation assay where the target cells were initiated with
      sub-threshold dose of 3-methylcholanthrene, confirming that Bhas 42 cells behave
      as initiated cells in the transformation assay.

PMID- 19386251
TI  - Effect of PCB153 on BaP-induced genotoxicity in HepG2 cells via modulation of
      metabolic enzymes.
AB  - Benzo(a)pyrene (BaP) is a representative environmental carcinogen and is
      metabolically activated by several cytochrome P450 (CYP) enzymes to become the
      ultimate carcinogen. Numerous studies have indicated that 2,2',4,4',5,5'
      hexachlorobiphenyl (PCB153) could effectively alter the activity of xenobiotic
      metabolizing enzymes (XMEs). Therefore, we propose that PCB153 may affect BaP
      induced genotoxicity mediated by XMEs. In the present study, we treated HepG2
      cells with BaP (50 microM) or PCB153 (0.1, 1, 10 and 100 microM), or pretreated
      the cells with PCB153 for 48 h followed by treatment with a combination of both
      BaP and PCB153. CYP1A1 activity was dramatically increased in cells treated with
      either BaP or PCB153. Glutathione-S-transferase (GST) activity was increased in
      BaP-treated cells, but decreased in PCB153-treated cells. In parallel to studies
      on enzyme activity, the micronuclei (MN) assay was used to assess the genotoxic
      damage caused by BaP and PCB153. BaP and PCB153 at 100 microM enhanced MN
      formation. In contrast to BaP treatment alone, treatment with both BaP and PCB153
      significantly enhanced the activity of CYP1A1 and the formation of MN, but
      reduced the activity of GST. alpha-Naphthoflavone (ANF), an inhibitor of CYP1A1,
      inhibited MN formation in the presence of both BaP and PCB153. In addition, there
      was a positive correlation between CYP1A activity and MN formation (r(2)=0.794,
      P<0.001). Our observations suggest that co-exposure to BaP and PCB153 may
      increase BaP-induced genotoxicity, possibly through the induction of CYP1A1 and
      inhibition of GST.

PMID- 19386252
TI  - Reticulocyte and micronucleated reticulocyte responses to gamma irradiation:
      effect of age.
AB  - The effect of age on the formation of radiation-induced micronucleated
      reticulocytes (MN-RETs) and reticulocytes (RETs) was investigated by exposing
      female C57BL/6J mice to graded doses of gamma rays from a (137)Cs source. Age at
      time of irradiation was 6, 16, or 32 weeks, and doses ranged from 0.5 to 3 Gy. A
      flow cytometric technique based on anti-CD71 labeling was used to measure RET and
      MN-RET frequencies in blood specimens collected 43 h post-irradiation. Mean RET
      frequencies declined in a dose-dependent manner for each age group. There was
      only one significant difference among the ages, that is, %RETs were not
      significantly reduced in the oldest animals at 0.5 Gy, whereas this dose did have
      a significant effect on the other age groups. MN-RET data were more complex. Age
      was observed to influence the baseline frequency of MN-RET, with the oldest mice
      exhibiting a significantly higher mean value. Each group's %MN-RETs values
      increased up to 1 Gy, but past this dose the frequencies plateaued or decreased.
      Age was observed to influence micronucleus frequency, with older mice exhibiting
      higher mean MN-RET values, especially at the high doses where the response was
      saturated (2-3 Gy). We hypothesize that these dissimilar responses can largely be
      explained by an age-related down-regulation of apoptosis whereby younger animals
      eliminate damaged bone marrow erythroid precursors with a greater efficiency
      compared with aged mice.

PMID- 19386253
TI  - Micronuclei and shisha/goza smoking in Egypt.

PMID- 19386254
TI  - SAT in silence.
AB  - X chromosome inactivation triggered by Xist RNA can only occur in specific
      developmental contexts. In this issue of Developmental Cell, Agrelo et al. show
      that the nuclear matrix protein SATB1 is a critical determinant of Xist
      responsiveness.

PMID- 19386255
TI  - Diversity of polyubiquitin chains.
AB  - Polyubiquitin chains linked through different lysines of ubiquitin may exert both
      proteasome-dependent and -independent functions. In a recent Cell issue, Xu et
      al. employ quantitative proteomics to profile polyubiquitin linkages in yeast.
      They find that linkages through all lysines of ubiquitin, except lysine-63, can
      target proteasomal degradation in vivo, and that lysine-11 polyubiquitination is
      important for endoplasmic reticulum-associated degradation (ERAD).

PMID- 19386256
TI  - Semiconserved regulation of mesendoderm differentiation by microRNAs.
AB  - MicroRNAs are known to play important roles in many different processes. However,
      their roles in shaping the early steps in embryogenesis have remained largely
      hidden. In this issue of Developmental Cell, Rosa et al. show that the miR
      430/427/302 family of microRNAs has a distinct effect on Nodal signaling,
      affecting mesendoderm differentiation in Xenopus embryos and human embryonic cell
      lines.

PMID- 19386257
TI  - Fibroblast "cilia growth" factor in the development of left-right asymmetry.
AB  - Although fibroblast growth factor (FGF) signaling is critical for many
      developmental processes, the cellular mechanism(s) by which FGF exerts its
      effects remains obscure. In recent papers, Neugebauer et al. and Hong and Dawid
      focus on the role of FGF signaling on left-right axis patterning, showing that
      FGF functions at least in part via an effect on ciliogenesis.

PMID- 19386258
TI  - Epithelial polarity: dual Lkb1 pathways regulate apical microvilli.
AB  - The Lkb1/Strad/Mo25 complex can polarize single epithelial cells, leading to the
      formation of a brush border containing microvilli on the apical surface. In this
      issue of Developmental Cell, ten Klooster et al. show that the Lkb1/Strad/Mo25
      complex mediates two separate pathways, and that both are required for assembly
      of apical microvilli.

PMID- 19386259
TI  - Septins and the lateral compartmentalization of eukaryotic membranes.
AB  - Eukaryotic cells from neurons and epithelial cells to unicellular fungi
      frequently rely on cellular appendages such as axons, dendritic spines, cilia,
      and buds for their biology. The emergence and differentiation of these appendages
      depend on the formation of lateral diffusion barriers at their bases to insulate
      their membranes from the rest of the cell. Here, we review recent progress
      regarding the molecular mechanisms and functions of such barriers. This overview
      underlines the importance and conservation of septin-dependent diffusion
      barriers, which coordinately compartmentalize both plasmatic and internal
      membranes. We discuss their role in memory establishment and the control of
      cellular aging.

PMID- 19386260
TI  - SATB1 defines the developmental context for gene silencing by Xist in lymphoma
      and embryonic cells.
AB  - The noncoding Xist RNA triggers silencing of one of the two female X chromosomes
      during X inactivation in mammals. Gene silencing by Xist is restricted to a
      special developmental context in early embryos and specific hematopoietic
      precursors. Here, we show that Xist can initiate silencing in a lymphoma model.
      We identify the special AT-rich binding protein SATB1 as an essential silencing
      factor. Loss of SATB1 in tumor cells abrogates the silencing function of Xist. In
      lymphocytes Xist localizes along SATB1-organized chromatin and SATB1 and Xist
      influence each other's pattern of localization. SATB1 and its homolog SATB2 are
      expressed during the initiation window for X inactivation in ES cells.
      Importantly, viral expression of SATB1 or SATB2 enables gene silencing by Xist in
      embryonic fibroblasts, which normally do not provide an initiation context. Thus,
      our data establish SATB1 as a crucial silencing factor contributing to the
      initiation of X inactivation.

PMID- 19386261
TI  - The miR-430/427/302 family controls mesendodermal fate specification via species
      specific target selection.
AB  - The role of microRNAs in embryonic cell fate specification is largely unknown. In
      vertebrates, the miR-430/427/302 family shows a unique expression signature and
      is exclusively expressed during early embryogenesis. Here, we comparatively
      address the embryonic function of miR-302 in human embryonic stem cells (hESCs)
      and its ortholog miR-427 in Xenopus laevis. Interestingly, we found that this
      miRNA family displays species-specific target selection among ligands of the
      Nodal pathway, with a striking conservation of the inhibitors, Lefties, but
      differential targeting of the activators, Nodals. The Nodal pathway plays a
      crucial role in germ layer specification. Accordingly, by gain and loss of
      function experiments in hESCs, we show that miR-302 promotes the mesendodermal
      lineage at the expense of neuroectoderm formation. Similarly, depletion of miR
      427 in Xenopus embryos hinders the organizer formation and leads to severe dorsal
      mesodermal patterning defects. These findings suggest a crucial role for the miR
      430/427/302 family in vertebrate embryogenesis by controlling germ layer
      specification.

PMID- 19386262
TI  - SRp38 regulates alternative splicing and is required for Ca(2+) handling in the
      embryonic heart.
AB  - SRp38 is an atypical SR protein splicing regulator. To define the functions of
      SRp38 in vivo, we generated SRp38 null mice. The majority of homozygous mutants
      survived only until E15.5 and displayed multiple cardiac defects. Evaluation of
      gene expression profiles in the SRp38(-/-) embryonic heart revealed a defect in
      processing of the pre-mRNA encoding cardiac triadin, a protein that functions in
      regulation of Ca(2+) release from the sarcoplasmic reticulum during excitation
      contraction coupling. This defect resulted in significantly reduced levels of
      triadin, as well as those of the interacting protein calsequestrin 2. Purified
      SRp38 was shown to bind specifically to the regulated exon and to modulate
      triadin splicing in vitro. Extending these results, isolated SRp38(-/-) embryonic
      cardiomyocytes displayed defects in Ca(2+) handling compared with wild-type
      controls. Taken together, our results demonstrate that SRp38 regulates cardiac
      specific alternative splicing of triadin pre-mRNA and, reflecting this, is
      essential for proper Ca(2+) handling during embryonic heart development.

PMID- 19386264
TI  - Mst4 and Ezrin induce brush borders downstream of the Lkb1/Strad/Mo25
      polarization complex.
AB  - The human Lkb1 kinase, encoded by the ortholog of the invertebrate Par4 polarity
      gene, is mutated in Peutz-Jeghers cancer syndrome. Lkb1 activity requires complex
      formation with the pseudokinase Strad and the adaptor protein Mo25. The complex
      can induce complete polarization in a single isolated intestinal epithelial cell.
      We describe an interaction between Mo25alpha and a human serine/threonine kinase
      termed Mst4. A homologous interaction occurs in the yeast Schizosaccharomyces
      pombe in the control of polar tip growth. Human Mst4 translocates from the Golgi
      to the subapical membrane compartment upon activation of Lkb1. Inhibition of Mst4
      activity inhibits Lkb1-induced brush border formation, whereas other aspects of
      polarity such as the formation of lateral junctions remain unaffected. As an
      essential event in brush border formation, Mst4 phosphorylates the regulatory
      T567 residue of Ezrin. These data define a brush border induction pathway
      downstream of the Lkb1/Strad/Mo25 polarization complex, yet separate from other
      polarity events.

PMID- 19386263
TI  - Plk1-dependent and -independent roles of an ODF2 splice variant, hCenexin1, at
      the centrosome of somatic cells.
AB  - Outer dense fiber 2 (ODF2) was initially identified as a major component of the
      sperm tail cytoskeleton, and was later suggested to be localized to somatic
      centrosomes and required for the formation of primary cilia. Here we show that a
      splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently
      localizes to somatic centrosomes via a variant-specific C-terminal extension and
      recruits Plk1 through a Cdc2-dependent phospho-S796 motif within the extension.
      This interaction and Plk1 activity were important for proper recruitment of
      pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar
      spindles. Earlier in the cell cycle, hCenexin1, but again not hODF2, also
      contributed to centrosomal recruitment of ninein and primary cilia formation
      independent of Plk1 interaction. These findings provide a striking example of how
      a splice-generated C-terminal extension of a sperm tail-associating protein
      mediates unanticipated centrosomal events at distinct stages of the somatic cell
      cycle.

PMID- 19386265
TI  - Linking asymmetric cell division to the terminal differentiation program of
      postmitotic neurons in C. elegans.
AB  - How asymmetric divisions are connected to the terminal differentiation program of
      neuronal subtypes is poorly understood. In C. elegans, two homeodomain
      transcription factors, TTX-3 (a LHX2/9 ortholog) and CEH-10 (a CHX10 ortholog),
      directly activate a large battery of terminal differentiation genes in the
      cholinergic interneuron AIY. We establish here a transcriptional cascade linking
      asymmetric division to this differentiation program. A transient lineage-specific
      input formed by the Zic factor REF-2 and the bHLH factor HLH-2 directly activates
      ttx-3 expression in the AIY mother. During the terminal division of the AIY
      mother, an asymmetric Wnt/beta-catenin pathway cooperates with TTX-3 to directly
      restrict ceh-10 expression to only one of the two daughter cells. TTX-3 and CEH
      10 automaintain their expression, thereby locking in the differentiation state.
      Our study establishes how transient lineage and asymmetric division inputs are
      integrated and suggests that the Wnt/beta-catenin pathway is widely used to
      control the identity of neuronal lineages.

PMID- 19386266
TI  - Integration of telencephalic Wnt and hedgehog signaling center activities by
      Foxg1.
AB  - The forebrain is patterned along the dorsoventral (DV) axis by Sonic Hedgehog
      (Shh). However, previous studies have suggested the presence of an Shh
      independent mechanism. Our study identifies Wnt/beta-catenin-activated from the
      telencephalic roof-as an Shh-independent pathway that is essential for
      telencephalic pallial (dorsal) specification during neurulation. We demonstrate
      that the transcription factor Foxg1 coordinates the activity of two signaling
      centers: Foxg1 is a key downstream effector of the Shh pathway during induction
      of subpallial (ventral) identity, and it inhibits Wnt/beta-catenin signaling
      through direct transcriptional repression of Wnt ligands. This inhibition
      restricts the dorsal Wnt signaling center to the roof plate and consequently
      limits pallial identities. Concomitantly to these roles, Foxg1 controls the
      formation of the compartment boundary between telencephalon and basal
      diencephalon. Altogether, these findings identify a key direct target of Foxg1,
      and uncover a simple molecular mechanism by which Foxg1 integrates two opposing
      signaling centers.

PMID- 19386267
TI  - Establishment of intestinal identity and epithelial-mesenchymal signaling by
      Cdx2.
AB  - We demonstrate that conditional ablation of the homeobox transcription factor
      Cdx2 from early endoderm results in the replacement of the posterior intestinal
      epithelium with keratinocytes, a dramatic cell fate conversion caused by ectopic
      activation of the foregut/esophageal differentiation program. This anterior
      homeotic transformation of the intestine was first apparent in the early
      embryonic Cdx2-deficient gut by a caudal extension of the expression domains of
      several key foregut endoderm regulators. While the intestinal transcriptome was
      severely affected, Cdx2 deficiency only transiently modified selected posterior
      Hox genes and the primary enteric Hox code was maintained. Further, we
      demonstrate that Cdx2-directed intestinal cell fate adoption plays an important
      role in the establishment of normal epithelial-mesenchymal interactions, as
      multiple signaling pathways involved in this process were severely affected. We
      conclude that Cdx2 controls important aspects of intestinal identity and
      development, and that this function is largely independent of the enteric Hox
      code.

PMID- 19386268
TI  - Fgf-dependent Etv4/5 activity is required for posterior restriction of Sonic
      Hedgehog and promoting outgrowth of the vertebrate limb.
AB  - Crosstalk between the fibroblast growth factor (FGF) and Sonic Hedgehog (Shh)
      pathways is critical for proper patterning and growth of the developing limb bud.
      Here, we show that FGF-dependent activation of the ETS transcription factors Etv4
      and Etv5 contributes to proximal-distal limb outgrowth. Surprisingly, blockage of
      Etv activity in early distal mesenchyme also resulted in ectopic, anterior
      expansion of Shh, leading to a polydactylous phenotype. These data indicate an
      unexpected function for an FGF/Etv pathway in anterior-posterior patterning. FGF
      activity in the limb is not only responsible for maintaining posterior-specific
      Shh expression, but it also acts via Etvs to prevent inappropriate anterior
      expansion of Shh. This study identifies another level of genetic interaction
      between the orthogonal axes during limb development.

PMID- 19386269
TI  - FGF-regulated Etv genes are essential for repressing Shh expression in mouse limb
      buds.
AB  - Anterior-posterior (A-P) patterning of the vertebrate limb is controlled by sonic
      hedgehog (SHH) signaling, and the precise restriction of Shh expression to the
      posterior limb bud is essential for its polarizing effect. Fibroblast growth
      factor (FGF) signaling, a key control of proximal-distal (P-D) limb outgrowth, is
      known to promote Shh expression in the posterior limb bud. Here, we show that
      conditional knockout of the FGF-activated transcription factor genes Etv4 and
      Etv5 in mouse led to ectopic Shh expression in the anterior limb bud and a
      preaxial polydactyly (PPD) skeletal phenotype. These unexpected results suggest
      that ETV4 and ETV5 act downstream of FGF signaling to inhibit Shh expression in
      the anterior limb bud. This finding elucidates a novel aspect of the mechanism
      coordinating limb development along the A-P and P-D axes.

PMID- 19386270
TI  - Inhibition of endothelial cell apoptosis by netrin-1 during angiogenesis.
AB  - Netrin-1 was recently proposed to play an important role in embryonic and
      pathological angiogenesis. However, data reported led to the apparently
      contradictory conclusions that netrin-1 is either a pro- or an antiangiogenic
      factor. Here, we reconcile these opposing observations by demonstrating that
      netrin-1 acts as a survival factor for endothelial cells, blocking the
      proapoptotic effect of the dependence receptor UNC5B and its downstream death
      signaling effector, the serine/threonine kinase DAPK. The netrin-1 effect on
      blood vessel development is mimicked by caspase inhibitors in ex vivo assays, and
      the inhibition of caspase activity, the silencing of the UNC5B receptor, and the
      silencing of DAPK are each sufficient to rescue the vascular sprouting defects
      induced by netrin-1 silencing in zebrafish. Thus, the proapoptotic effect of
      unbound UNC5B and the survival effect of netrin-1 on endothelial cells finely
      tune the angiogenic process.

PMID- 19386271
TI  - Central administration of palmitoylethanolamide reduces hyperalgesia in mice via
      inhibition of NF-kappaB nuclear signalling in dorsal root ganglia.
AB  - Despite the clear roles played by peroxisome proliferators-activated receptor
      alpha (PPAR-alpha) in lipid metabolism, inflammation and feeding, the effects of
      its activation in the central nervous system (CNS) are largely unknown.
      Palmitoylethanolamide (PEA), a member of the fatty-acid ethanolamide family, acts
      peripherally as an endogenous PPAR-alpha agonist, exerting analgesic and anti
      inflammatory effects. Both PPAR-alpha and PEA are present in the CNS, but the
      specific functions of this lipid and its receptor remain to be clarified. Using
      the carrageenan-induced paw model of hyperalgesia in mice, we report here that
      intracerebroventricular administration of PEA (0.1-1 microg) 30 min before
      carrageenan injection markedly reduced mechanical hyperalgesia up to 24 h
      following inflammatory insult. This effect was mimicked by GW7647 (1 microg), a
      synthetic PPAR-alpha agonist. The obligatory role of PPAR-alpha in mediating
      PEA's actions was confirmed by the lack of anti-hyperalgesic effects in mutant
      mice lacking PPAR-alpha. PEA significantly reduced the expression of
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in sciatic
      nerves and restored carrageenan-induced reductions of PPAR-alpha in the L4-L6
      dorsal root ganglia (DRG). To investigate the mechanism by which PEA attenuated
      hyperalgesia, we evaluated inhibitory kB-alpha (IkB-alpha) degradation and p65
      nuclear factor kB (NF-kappaB) activation in DRG. PEA prevented IkB-alpha
      degradation and p65 NF-kappaB nuclear translocation, confirming the involvement
      of this transcriptional factor in the control of peripheral hyperalgesia. These
      results add further support to the broad-spectrum of biological and
      pharmacological effects induced by PPAR-alpha agonists, suggesting a centrally
      mediated component for these drugs in controlling inflammatory pain.

PMID- 19386272
TI  - Polymer micelles with cross-linked polyanion core for delivery of a cationic drug
      doxorubicin.
AB  - Polymer micelles with cross-linked ionic cores were prepared by using block
      ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA)
      copolymer and divalent metal cations as templates. Doxorubicin (DOX), an
      anthracycline anticancer drug, was successfully incorporated into the ionic cores
      of such micelles via electrostatic interactions. A substantial drug loading level
      (up to 50 w/w%) was achieved and it was strongly dependent on the structure of
      the cross-linked micelles and pH. The drug-loaded micelles were stable in aqueous
      dispersions exhibiting no aggregation or precipitation for a prolonged period of
      time. The DOX-loaded polymer micelles exhibited noticeable pH-sensitive behavior
      with accelerated release of DOX in acidic environment due to the protonation of
      carboxylic groups in the cores of the micelles. The attempt to protect the DOX
      loaded core with the polycationic substances resulted in the decrease of loading
      efficacy and had a slight effect on the release characteristics of the micelles.
      The DOX-loaded polymer micelles exhibited a potent cytotoxicity against human
      A2780 ovarian carcinoma cells. These results point to a potential of novel
      polymer micelles with cross-linked ionic cores to be attractive carriers for the
      delivery of DOX.

PMID- 19386273
TI  - Nanotoxicity assessment: all small talk?

PMID- 19386274
TI  - Nonviral vector-mediated RNA interference: its gene silencing characteristics and
      important factors to achieve RNAi-based gene therapy.
AB  - RNA interference (RNAi) is a potent and specific gene silencing event in which
      small interfering RNA (siRNA) degrades target mRNA. Therefore, RNAi is of
      potential use as a therapeutic approach for the treatment of a variety of
      diseases in which aberrant expression of mRNA causes a problem. RNAi can be
      achieved by delivering siRNA or vectors that transcribe siRNA or short-hairpin
      RNA (shRNA). The aim of this review is to examine the potential of nonviral
      vector-mediated RNAi technology in treating diseases. The characteristics of
      plasmid DNA expressing shRNA were compared with those of siRNA, focusing on the
      duration of gene silencing, delivery to target cells and target specificity.
      Recent progresses in prolonging the RNAi effect, improving the delivery to target
      cells and increasing the specificity of RNAi in vivo are also reviewed.

PMID- 19386275
TI  - Effects of nanomaterial physicochemical properties on in vivo toxicity.
AB  - It is well recognized that physical and chemical properties of materials can
      alter dramatically at nanoscopic scale, and the growing use of nanotechnologies
      requires careful assessment of unexpected toxicities and biological interactions.
      However, most in vivo toxicity concerns focus primarily on pulmonary, oral, and
      dermal exposures to ultrafine particles. As nanomaterials expand as therapeutics
      and as diagnostic tools, parenteral administration of engineered nanomaterials
      should also be recognized as a critical aspect for toxicity consideration. Due to
      the complex nature of nanomaterials, conflicting studies have led to different
      views of their safety. Here, the physicochemical properties of four
      representative nanomaterials (dendrimers, carbon nanotubes, quantum dots, and
      gold nanoparticles) as it relates to their toxicity after systemic exposure is
      discussed.

PMID- 19386276
TI  - A functional polymorphism in estrogen receptor alpha gene is associated with
      Japanese methamphetamine induced psychosis.
AB  - BACKGROUND: A recent study reported an association between rs2234693, which
      influences enhancer activity levels in estrogen receptor alpha gene (ESR1), and
      schizophrenia. This study reported that schizophrenic patients with the CC
      genotype have significantly lower ESR1 mRNA levels in the prefrontal cortex than
      patients with other genotypes. The symptoms of methamphetamine induced psychosis
      are similar to those of paranoid type schizophrenia. Therefore, we conducted an
      association analysis of rs2234693 with Japanese methamphetamine induced psychosis
      patients. METHOD: Using rs2234693, we conducted a genetic association analysis of
      case-control samples (197 methamphetamine induced psychosis patients and 197
      healthy controls). The age and sex of the control subjects did not differ from
      those of the methamphetamine induced psychosis patients. RESULTS: We detected a
      significant association between ESR1 and methamphetamine induced psychosis
      patients in allele/genotype-wise analysis. For further interpretation of these
      associations, we performed single marker analysis of subjects divided by sex.
      Rs2234693 was associated with male methamphetamine induced psychosis. DISCUSSION:
      Our results suggest that rs2234693 in ESR1 may play a role in the pathophysiology
      of Japanese methamphetamine induced psychosis patients.

PMID- 19386277
TI  - Association analysis of group II metabotropic glutamate receptor genes (GRM2 and
      GRM3) with mood disorders and fluvoxamine response in a Japanese population.
AB  - BACKGROUND: Several lines of evidence implicate abnormalities in glutamate neural
      transmission in the pathophysiology of mood disorders, including major depressive
      disorder (MDD) and bipolar disorder (BP). Preclinical antidepressant effects were
      also reported for group II metabotropic glutamate receptor (Group II mGluRs)
      antagonists show dose-dependent antidepressant-like effects in murine models of
      depression. Also, it has been suggested that abnormalities in the hypothalamic
      pituitary-adrenal axis and serotonergic neural transmission are important
      mechanisms in the pathophysiology of mood disorders. Group II mGluRs play an
      important role in regulating the function of these mechanisms. From these
      results, it has been suggested that abnormalities in Group II mGluRs might be
      involved in the pathophysiology of mood disorders, including MDD) and BP, and may
      influence the clinical response to treatment with SSRIs in MDD. Therefore, we
      studied the association between Group II mGluR genes (GRM2 and GRM3) and mood
      disorders and the efficacy of fluvoxamine treatment in Japanese MDD patients.
      MATERIALS AND METHODS: Using three tagging SNPs in GRM2 and an SNP (rs6465084)
      reported functional variant in GRM3, we conducted a genetic association analysis
      of case-control samples (325 MDD patients, 155 BP patients and 802 controls) in
      the Japanese population. In addition, we performed an association analysis of
      GRM2 and GRM3 and the efficacy of fluvoxamine treatment in 117 Japanese patients
      with MDD. The MDD patients in this study had scores of 12 or higher on the 17
      items of the Structured Interview Guide for Hamilton Rating Scale for Depression
      (SIGH-D). We defined a clinical response as a decrease of more than 50% in
      baseline SIGH-D within 8 weeks, and clinical remission as an SIGH-D score of less
      than 7 at 8 weeks. RESULTS: We found an association between rs6465084 in GRM3 and
      MDD in the allele-wise analysis after Bonferroni's correction (P-value=0.0371).
      However, we did not find any association between GRM3 and BP or the fluvoxamine
      therapeutic response in MDD in the allele/genotype-wise analysis. We also did not
      detect any association between GRM2 and MDD, BP or the fluvoxamine therapeutic
      response in MDD in the allele/genotype-wise or haplotype-wise analysis.
      DISCUSSION: We detected an association between only one marker (rs6465084) in
      GRM3 and Japanese MDD patients. However, because we did not perform an
      association analysis based on LD and a mutation scan of GRM3, a replication study
      using a larger sample and based on LD may be required for conclusive results.

PMID- 19386278
TI  - Effects of mono and di(n-butyl) phthalate on superoxide dismutase.
AB  - Di(n-butyl) phthalate (DBP) is a plasticizer used in the manufacture of several
      industrial and household articles. They get easily released to the environment
      and may cause adverse effects to living organisms. Effects of DBP and its
      metabolite monobutyl phthalate (MBP) on superoxide dismutase (SOD), an
      antioxidant enzyme, have been studied. When SOD was incubated with varying amount
      of DBP the activity of the enzyme was decreased proportionate to the
      concentration of the phthalates added. A similar result was observed with MBP
      also. These indicate that the DBP and MBP possess concentration dependent
      inhibitory effect on SOD. The mode of interaction of DBP and MBP has also been
      investigated using modeling and docking studies. The docking results showed that
      both DBP and MBP can bind in the active site of SOD and can make hydrogen bonds
      with the active site residue R143. This residue is crucial in the binding of
      reactive oxygen species (ROS) during its conversion to hydrogen peroxide and
      molecular oxygen. This may perhaps explain the inhibitory effect of DBP and MBP
      on SOD.

PMID- 19386279
TI  - Expression of metallothionein mRNAs on mouse cerebellum microglia cells by
      thimerosal and its metabolites.
AB  - Effects of thimerosal and its metabolites, ethyl mercury and thiosalicylate, on
      the expression of metallothionein (MT) mRNAs in mouse cerebellum microglia cell
      line, C8-B4 cells, were studied. The level of MT-1 mRNA significantly decreased
      at early hours and recovered time-dependently 24h after thimerosal was added to
      the C8-B4 cells. However, MT-2 and MT-3 mRNA expressions did not change from the
      control group. In contrast, the expression of MT-1 mRNA increased in a mouse
      neuroblastoma cell line 6h after incubation with thimerosal. In addition, the
      level of MT-1 mRNA decreased in C8-B4 cells 6h after the addition of
      thiosalicylate, but ethyl mercury induced MT-1 mRNA expression. When cell
      viability was compared with thimerosal, thiosalicylate, and ethyl mercury, the
      viability of C8-B4 cells decreased dose-dependently 24h after either thimerosal
      or ethyl mercury was added; however, the viability increased dose-dependently
      until 15 microM thiosalicylate was added. From the present results, it is
      concluded that the expression of MT-1 mRNA may be mediated by different factors
      than the expression of MT-2 mRNA in C8-B4 cells. The reduction of MT-1 mRNA level
      by thiosalicylate may affect the proliferation of C8-B4 cells.

PMID- 19386280
TI  - Clinical picture of sulfur mustard poisoning.

PMID- 19386281
TI  - Myocardial heat shock protein 60 expression is upregulated following acute
      cardiac rejection.
AB  - BACKGROUND: Heat shock proteins (HSPs) are endogenous adjuvants which are
      upregulated following cellular injury. HSP60 may be upregulated in response to
      myocardial injury, inducing activation via TLR ligation on monocytes, dendritic
      cells and T cells. On these grounds, this study was designed to assess HSP60
      expression during the rejection process following cardiac transplantation.
      METHODS: Intracellular and cell surface endomyocardial concentration of HSP60 was
      quantified longitudinally in a cohort of heart transplant recipients (n = 17, 54
      biopsy samples) using competitive sandwich ELISA. RESULTS: HSP 60 concentration
      was low before and during an acute rejection episode. Surprisingly an increase of
      HSP60 was observed in the period following rejection during recovery (p = 0.026).
      CONCLUSIONS: This novel data demonstrates that human endomyocardial HSP60 is
      increased following an acute rejection episode. This may occur following
      endomyocardial damage as a result of immune cell infiltration and graft cell
      damage. However, in contrast to the general assumption that this molecule
      represents a danger signal, our findings suggest HSP60 expression may be induced
      as part of a protective response following tissue damage.

PMID- 19386282
TI  - Penehyclidine hydrochloride attenuates LPS-induced acute lung injury involvement
      of NF-kappaB pathway.
AB  - To investigate the protective effects of penehyclidine hydrochloride (PHC) in
      lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the underlying
      molecular mechanism. ALI was induced by intravenous injection of LPS (5mg/kg).
      Male Sprague-Dawley (SD) rats challenged with or without LPS were pretreated with
      varied doses of PHC 0.5h before injection of LPS or saline. Blood gas in arterial
      blood, lung weight gain, bronchoalveolar lavage fluid (BALF), and neutrophils
      sequestration were examined 6h after administration of LPS. Pathological changes
      of lung tissue were measured by light microscopy. Phosphorylation of mitogen
      activated protein kinase (MAPK) family and NF-kappaB were detected by western
      blot. All animals demonstrated drops in arterial oxygen tension (PaO(2)) after
      LPS application, which were significantly reversed by PHC pretreatment.
      Administration of PHC reduced lung water gain, bronchoalveolar lavage protein
      content, infiltration of neutrophils, malondialdehyde (MDA) content, and lactate
      dehydrogenase (LDH) activity and enhanced superoxide dismutase (SOD) activity.
      Histopathological study also indicated that PHC treatment markedly attenuated
      lung histopathological changes, alveolar hemorrhage, and inflammatory cells
      infiltration with evidence of decreasing of myeloperoxidase (MPO) activity.
      Furthermore, p38MAPK, ERK, and NF-kappaB were activated in 6h after LPS
      treatment, which could be blunted by PHC, while JNK remained unchanged. These
      findings confirmed significant protection by PHC against LPS-induced lung
      vascular leak and inflammation and implicated inhibition of p38MAPK activation
      signaling a potential role for PHC in the management of ALI.

PMID- 19386283
TI  - Sildenafil therapy in secondary pulmonary hypertension: Is there benefit in
      prolonged use?
AB  - BACKGROUND: Sildenafil is of benefit to selected patients with pulmonary
      hypertension due to parenchymal lung or cardiac disease. We present data from
      patients with secondary pulmonary hypertension, comparing their right heart
      catheter results and six minute walking distance to time on treatment. METHODS:
      25 patients with symptomatic secondary pulmonary hypertension received sildenafil
      50 mg tds in a 5-year period. Underlying causes were chronic inoperable
      thromboembolic disease (11), COPD (6), interstitial lung disease (5) and valvular
      heart disease (3). Their cardio-pulmonary haemodynamics were measured with right
      heart catheterization prior to treatment, post-treatment at 2, 6 and 12 months
      and subsequently depending upon clinical need. Six-minute walk distance was also
      measured. RESULTS: Patient age range was 40 to 83 (median 70.5) years. Time of
      treatment to latest right heart catheter was 2 to 60 (median 17) months and 8 to
      61 (median 34) months to clinic follow-up or death. There was a significant
      reduction in six-minute walk distance from baseline to long term (>12 months)
      follow-up (p=0.002). Pulmonary vascular resistance was significantly reduced from
      baseline to 12 months (p=0.049). The mean pulmonary arterial (PA) pressure was
      significantly reduced at long-term follow-up (p=0.009). 20 patients had an
      improved PA pressure with treatment. In those with a worsening PA pressure, two
      had an improvement in cardiac output and six minute walk distance, two had stable
      cardiac output at 20 and 21 months, and one had measurements taken during a
      significant illness. Three patients, who had a reduction in PA pressure,
      subsequently died of progression of underlying illness at 8 months, from
      myocardial infarction at 34 months, and from aspergillus pneumonia at 59 months.
      CONCLUSION: Long-term use of sildenafil in patients with secondary forms of
      pulmonary hypertension is associated with a sustained improvement in cardio
      pulmonary haemodynamics. Lack of improvement may be attributed to other factors
      apart from treatment failure, such as underlying disease progression or unrelated
      concurrent illness at time of assessment.

PMID- 19386284
TI  - Post-transcriptional silencing of TRPC1 ion channel gene by RNA interference
      upregulates TRPC6 expression and store-operated Ca2+ entry in A7r5 vascular
      smooth muscle cells.
AB  - This study investigates functional consequences of TRPC1 ion channel
      downregulation observed in aging rat aorta by employing RNA interference in
      cultured vascular smooth muscle cells. For this purpose, A7r5 aortic smooth
      muscle cells were used in quantitative gene and protein expression as well as in
      functional analyses. According to quantitative RT-PCR results, TRPC3, TRPC4 and
      TRPC5 mRNAs were not at detectable levels. In siTRPC1-transfected cells, TRPC1
      mRNA and protein levels were decreased by 40% and 64%; however, those of TRPC6
      were drastically increased by 100% and 200%, respectively. In fura-2-loaded TRPC1
      knockdown cells, despite the decreased TRPC1 levels, cyclopiazonic acid-induced
      Ca2+ entry and store-operated Ca2+ entry following Ca2+ addition were elevated by
      77% and 135%, respectively. Results suggest that decrease in TRPC1 may be
      compensated by upregulated TRPC6 that possibly takes part in store-operated Ca2+
      entry in vascular smooth muscle cells.

PMID- 19386285
TI  - Intracluster correlation adjustments to maintain power in cluster trials for
      binary outcomes.
AB  - Adequately powered sample size calculations for cluster randomized trials
      primarily depend on the event rate variability, effect size, average cluster
      size, and intracluster correlation (ICC). Furthermore, an ICC estimate depends on
      event rate variability among clusters, cluster size, and number of clusters. We
      evaluated the impact on ICC estimates of event rates, event rate variations,
      cluster size, and cluster size variations for different numbers of clusters. We
      also evaluated how the event rate changes at the end of the trial affect ICC
      estimates. We created one simulation exercise to investigate how different event
      rates, event rate variations, cluster size, and cluster size variations impact
      ICC estimates and 95% confidence intervals. A separate simulation exercise in
      four different trial scenarios examined the impact of an intervention or drug
      effect in the intervention group on ICC estimates, 95% confidence intervals, and
      on sample size. The first simulation results suggest that the ICC value depends
      upon the event rate and event rate variations in addition to the cluster size,
      cluster size variations, and number of clusters. The second simulation exercise
      suggested that adjusting the sample size will help to preserve the appropriate
      power at the end of the trial.

PMID- 19386286
TI  - Antiphospholipid antibodies and malignancies.
AB  - Since the 1980s it is known that an important thrombogenic mechanism is mediated
      by antiphospholipid antibodies (aPL). Aim of this review is to discuss how much
      aPL presence may worsen the thrombophilic state of neoplastic patients and how
      much cancer may worsen and extend the thrombophilic state of patients with
      Antiphospholipid Syndrome (APS). In the last years a higher prevalence of aPL was
      observed in patients with solid tumors compared to controls. These patients,
      already at higher risk of thrombosis, may have a still higher risk when aPL
      carriers. Those with a solid malignancy seem to be more likely to have a
      thrombotic event compared to patients with a hematological disorder. On the other
      hand aPL presence may be a risk factor for malignancies (particularly
      hematological). Even if the significance of aPL and cancer relationship has to be
      further investigated, clinicians should remember that in neoplastic patients aPL
      presence can increase thromboembolic risk and in healthy carriers can increase
      the possibility of developing a malignancy.

PMID- 19386288
TI  - Acute rheumatic fever and its consequences: a persistent threat to developing
      nations in the 21st century.
AB  - Acute rheumatic fever (ARF) is an autoimmune, multi-system response secondary to
      molecular mimicry following Lancefield group A streptococcus (GAS) pharyngitis;
      it is now most commonly found in the pediatric populations of developing nations.
      The major source of morbidity and mortality of ARF stems from rheumatic heart
      disease (RHD), although the cardinal symptoms of the disease also include
      polyarthritis, Sydenham's chorea, subcutaneous nodules, and erythema marginatum.
      Therapy is aimed towards treating the initial GAS infection, using anti
      inflammatory medications for acute symptoms and surgery to correct RHD. Secondary
      prevention is crucial, given the high risk of recurrence, and includes long-term
      antibiotic prophylaxis. However, vaccination towards GAS may soon be on the
      horizon, which may assist in both decreasing the risk of initial infection in
      naive patients and helping to lower the risk of recurrence.

PMID- 19386287
TI  - Intravenous immunoglobulin as add on treatment with mycophenolate mofetil in
      severe myositis.
AB  - OBJECTIVES: To report the use of intravenous immunoglobulin (IVIg) and
      mycophenolate mofetil (MMF) in polymyositis (PM) and dermatomyositis (DM).
      METHODS: We performed an open study in PM and DM with active disease. Indications
      for treatment were: steroid-dependency, refractoriness to steroid and/or
      immunosuppressants, and life-threatening disease. IVIg was used at 2 g/kg in
      monthly cycles for six months and then each other month for other three cycles.
      MMF was slowly titrated to 30 mg/kg/day orally. Parameters employed to follow
      patients were the Medical Research Council (MRC) scale, the modified Rankin
      score, CK serum levels and daily prednisone dose. RESULTS: Seven patients were
      studied (4PM, 3DM). All were females, with a mean age of 49 years. All of them
      achieved a complete remission and, at the last follow-up visit, significant
      differences in MRC score, modified Rankin score, CK levels, and the daily
      maintenance prednisone dose were documented. No relevant side effects were
      observed. CONCLUSION: IVIg as add on treatment with MMF is effective in severe
      and refractory myositis, moreover as safe and steroid-sparing agent.

PMID- 19386291
TI  - Editor review of "Erythropoietin as a neuroprotective agent in traumatic brain
      injury" by Mammis et al.

PMID- 19386292
TI  - A brief history on determining occlusion of aneurysms by clips.

PMID- 19386293
TI  - The lesson of anatomy.

PMID- 19386295
TI  - Choosing to switch: spontaneous task switching despite associated behavioral
      costs.
AB  - The literature shows that switching among simple cognitive tasks is difficult and
      involves a performance cost. Accordingly, cost-benefit considerations seem to
      predict that task switching would not occur spontaneously. Here we show that
      spontaneous task switching is a robust phenomenon, despite its costs. In
      Experiment 1, participants had to judge shapes according to one of three possible
      dimensions. Importantly, they were given the option to choose another relevant
      dimension or let the computer program change the dimension for them, but only if
      they wanted to do so. The results showed that spontaneous task switching was
      prevalent, despite robust switching costs. Experiment 2 extended this finding in
      showing spontaneous switching from an easy task to a more difficult task. The
      authors provide two possible explanations for the phenomenon that posit that
      spontaneous switching may be unpreventable or even advantageous.

PMID- 19386296
TI  - [Preoperative corticosteroid treatment and nasal polyposis].
AB  - OBJECTIVES: Impairment of the surgical view by bleeding in endoscopic
      ethmoidectomy for chronic rhinosinusitis with nasal polyps (CRSwNP) contributes
      to the risk of skull base injuries. The aim of this study was to investigate the
      effect of a short course of a systemic corticoid treatment on bleeding and
      surgical field quality during endoscopic ethmoidectomy for CRSwNP. METHODS: A
      prospective study was conducted on 40 patients. Before surgery, 21 of them (group
      B) were treated with 1 mg/kg per day of prednisolone for seven days. They were
      compared with the 19 other patients (group A) on intraoperative blood loss and
      surgery duration. RESULTS: The two groups shared identical clinical features
      (Lidholdt endoscopic grading). There was no statistical difference in terms of
      bleeding, although the Lund-Mackay CT score was higher in group B (19/24 vs.
      21/24, p=0.05). The surgical procedure was shorter in group B (72 min vs. 85 min,
      p=0.05). CONCLUSION: Preoperative treatment with systemic corticosteroids does
      not seem to reduce surgical blood loss. However, we noted a decrease in the
      procedure's duration. By reducing mucous inflammation, this treatment could
      improve the local conditions and help the surgeon in the mucous eradication.

PMID- 19386297
TI  - Analog simulation of aortic and of mitral regurgitation.
AB  - By using an equivalent electronic circuit either mitral or aortic regurgitation
      was simulated. Simulation allowed not only a measurement of various pressures
      within the cardiovascular system and cardiac output, but also mitral and aortic
      flow. In normal conditions mitral and aortic flows were monophasic, anterograde.
      In valve regurgitation mitral and aortic flows were, as expected, biphasic. In
      mitral regurgitation, during systole and diastole the valve flow was retrograde
      and anterograde, respectively. In aortic regurgitation, during systole and
      diastole the valve flow was anterograde and retrograde, respectively. The
      magnitude of the regurgitant valve flow was measured by time-integration and
      compared to the net flow, i.e. cardiac output. Valve flow was determined not only
      by the magnitude of valve dysfunction, but also by the resistive/capacitive
      characteristics of the "falsely" attached regurgitant circuit. If the regurgitant
      valve flow was large enough, it in turn affected the function of the left
      ventricle. The present investigation suggests that many features observed in
      patients with mitral or aortic regurgitation can be qualitatively satisfactorily
      simulated. In some respects even quantitative simulation is possible. However,
      for simulation of chronic mitral or aortic regurgitation, in the analog
      electronic circuit additional adjustments-in capacitance of the left ventricle
      and pulmonary system--would be required.

PMID- 19386298
TI  - Classification of peptide mass fingerprint data by novel no-regret boosting
      method.
AB  - We have developed an integrated tool for statistical analysis of large-scale LC
      MS profiles of complex protein mixtures comprising a set of procedures for data
      processing, selection of biomarkers used in early diagnostic and classification
      of patients based on their peptide mass fingerprints. Here, a novel boosting
      technique is proposed, which is embedded in our framework for MS data analysis.
      Our boosting scheme is based on Hannan-consistent game playing strategies. We
      analyze boosting from a game-theoretic perspective and define a new class of
      boosting algorithms called H-boosting methods. In the experimental part of this
      work we apply the new classifier together with classical and state-of-the-art
      algorithms to classify ovarian cancer and cystic fibrosis patients based on
      peptide mass spectra. The methods developed here provide automatic, general, and
      efficient means for processing of large scale LC-MS datasets. Good classification
      results suggest that our approach is able to uncover valuable information to
      support medical diagnosis.

PMID- 19386299
TI  - Hedged predictions for traditional Chinese chronic gastritis diagnosis with
      confidence machine.
AB  - Most classifiers output predictions for new instances without indicating how
      reliable they could be. Transductive confidence machine (TCM) is a novel
      framework that provides hedged prediction coupled with valid confidence. Many
      popular machine learning algorithms can be transformed into the framework of TCM,
      and therefore be used for producing hedged predictions. This paper incorporates
      random forest (RF) to propose a method named TCM-RF for classification of chronic
      gastritis data. Our method benefits from TCM-RF's high performance when features
      are noisy, highly correlated and of mixed types. The experimental results show
      that TCM-RF produces informative as well as effective predictions.

PMID- 19386300
TI  - What factors currently limit magnetic resonance-guided focused ultrasound of
      leiomyomas? A survey conducted at the first international symposium devoted to
      clinical magnetic resonance-guided focused ultrasound.
AB  - OBJECTIVE: To see if clinicians' impressions were influenced by expert opinion on
      patient selection criteria that influence magnetic resonance-guided focused
      ultrasound (MRgFUS) leiomyoma treatment. DESIGN: Survey-based study. SETTING:
      First international symposium devoted to MRgFUS, "MRgFUS 2008," October 6-7,
      2008, Washington, DC. INTERVENTION(S): Questionnaires on fibroid treatment were
      distributed to attending practitioners before and after the symposium. MAIN
      OUTCOME MEASURE(S): Selection criteria, which could be considered to be
      limitations to focused ultrasound therapy, were assessed on a 10-point Likert
      scale ranging from 1, which indicated no impediment to therapy, to 10, which
      represented an absolute contraindication to therapy. RESULT(S): A total of 12
      paired pre- and post-symposium questionnaires were analyzed. Mild adenomyosis,
      heavy bleeding, and bulk complaint were viewed as least likely to be an
      impediment to therapy both before and after the symposium. The presence of severe
      adenomyosis and five or more fibroids showed significant increases in mean
      rankings as contraindications to therapy following the symposium. Significant
      adverse events not previously reported were elicited by the survey.
      CONCLUSION(S): Expert opinion on patient selection criteria for MRgFUS is a
      useful resource for practitioner education.

PMID- 19386301
TI  - Computer-aided learning in capsule endoscopy leads to improvement in lesion
      recognition ability.
AB  - BACKGROUND: The rapid expansion in use of capsule endoscopy (CE) has led to
      discussion about training needs and provision. The lesion recognition skills
      required for CE are ideally suited to computer-based training. OBJECTIVE: The aim
      of this study was to prospectively evaluate the educational effectiveness of a
      computer-based CE training and testing module on trainees with varying
      experience. DESIGN: This was a prospective educational evaluation study. SETTING:
      Academic endoscopy unit. PATIENTS: This study involved 28 trainees of varying CE
      experience (medical students, gastroenterology trainees) and 4 CE experts.
      INTERVENTION: Trainees (medical students and gastroenterology trainees) without
      CE experience completed a 60-question, computer-based test module consisting of
      30-second video clips and multiple-choice questions. Without feedback, trainees
      then completed a comprehensive, menu-driven, computer-based CE training module.
      The test module was then completed a second time and feedback was given. Expert
      performance on the test module was benchmarked by 4 CE experts. MAIN OUTCOME
      MEASUREMENTS: The first measure was the difference in baseline performance on the
      test module between trainees and experts (to determine construct validity). The
      second measure was a change in performance on the test module after training (to
      determine content validity of the training module). RESULTS: A significant
      difference was noted in baseline performance (P < .001) among CE experts (mean
      73.8% +/- 8.0%), gastroenterology trainees (49.5% +/- 10.9%), and medical
      students (29.5% +/- 3.3%). Performance improved significantly (P < .001) in both
      trainee groups after training (gastroenterology trainees' posttraining score
      62.1% +/- 7.7%; medical students' 46.7% +/- 6.8%). CONCLUSION: Computer-based
      learning has a potentially significant role in the development of a training
      syllabus for CE and in CE accreditation.

PMID- 19386302
TI  - Plexiform neurofibroma: an unusual cause of GI bleeding and intestinal
      obstruction.

PMID- 19386303
TI  - Gastric mucosal pattern by using magnifying narrow-band imaging endoscopy clearly
      distinguishes histological and serological severity of chronic gastritis.
AB  - BACKGROUND: Magnifying narrow-band imaging (NBI) endoscopy clearly visualizes
      superficial gastric mucosal patterns and capillary patterns. OBJECTIVE: To
      investigate gastric mucosal patterns by using magnifying NBI endoscopy and
      identify any relationship between those patterns and Helicobacter pylori-induced
      gastritis. DESIGN: Gastric mucosal patterns seen with magnifying NBI in
      uninvolved gastric corpus were divided into the following categories: normal-
      small, round pits with regular subepithelial capillary networks; type 1-slightly
      enlarged, round pits with unclear or irregular subepithelial capillary networks;
      type 2--obviously enlarged, oval or prolonged pits with increased density of
      irregular vessels; and type 3-well--demarcated oval or tubulovillous pits with
      clearly visible coiled or wavy vessels. SETTING: Department of Gastroenterology,
      Fujita Health University. PATIENTS: This study involved 106 participants
      undergoing upper endoscopy. RESULTS: H pylori infection-positive ratios of normal
      and types 1, 2, and 3 patterns were 7.5%, 92.9%, 94.5%, and 66.7%, respectively.
      Sensitivity and specificity for types 1 + 2 + 3 for detection of H pylori
      positivity and type 3 for detection of intestinal metaplasia were 95.2%, 82.2%,
      73.3%, and 95.6%, respectively. Development of mucosal patterns from normal to
      types 1, 2, and 3 was correlated with all histological parameters (P < .0001),
      lower pepsinogen I/II ratios (P < .0001), and degree of endoscopic atrophy (P <
      .0001). Sensitivity and specificity of type 3 for the prediction of severe
      histological atrophy was also better than those of serum pepsinogen level and
      standard endoscopy. LIMITATIONS: Only 1 endoscopist performed endoscopic
      procedures, and interobserver agreement could not be assessed. CONCLUSIONS:
      Magnifying NBI endoscopy is useful for predicting H pylori infection and the
      histological severity of gastritis and is valuable for predicting gastric atrophy
      in the entire stomach.

PMID- 19386304
TI  - Ultrathin endoscopy versus high-resolution endoscopy for diagnosing superficial
      gastric neoplasia.
AB  - BACKGROUND: Ultrathin endoscopy (UTE) is an acceptable and cost-effective
      alternative to EGD with the patient under sedation, although the diagnostic
      accuracy of UTE is not well established. OBJECTIVE: To compare the diagnostic
      accuracy of UTE and high-resolution endoscopy (HRE) for superficial gastric
      neoplasia. DESIGN: Prospective comparative study. SETTING: Academic center.
      PATIENTS AND INTERVENTIONS: Patients with or without superficial gastric
      neoplasia underwent peroral UTE and HRE, back-to-back in a random order while
      under standard sedation. The procedures were performed by 2 endoscopists who were
      blinded to the clinical information. MAIN OUTCOME MEASUREMENTS: The rate of
      missed lesions and misdiagnosis, sensitivity, and specificity for the diagnosis
      of gastric neoplasia when using pathology as the reference standard. RESULTS: In
      total, 126 lesions (41 superficial gastric neoplasias, 85 nonneoplastic lesions)
      were recorded in 57 enrolled patients. For the diagnosis of gastric neoplasia,
      the sensitivity of UTE (58.5%) was significantly (P = .021) lower than that of
      HRE (78%), and the specificity of UTE (91.8%) was significantly (P = .014) lower
      than that of HRE (100%). The rate of missed lesions and misdiagnosis of gastric
      neoplasias when using UTE (41.5%) was significantly (P > .001) higher than that
      of HRE (22.0%). The corresponding rate of neoplasias at the proximal portion
      (fornix and corpus) when using UTE (29%) was significantly (P = .002) higher than
      that of HRE (7.2%), although the rates of neoplasias at the distal portion
      (angulus and antrum) were comparable for UTE and HRE. LIMITATION: Small sample
      numbers in an enriched population. CONCLUSIONS: The diagnostic accuracy of UTE is
      significantly lower than that of HRE for superficial gastric neoplasia, and this
      difference is particularly striking for neoplasias in the proximal stomach. For
      UTE to be used as an alternative modality, improvements in optical quality and
      the incorporation of additional procedures, including close-range observations
      and chromoendoscopy, are required to enhance visualization.

PMID- 19386305
TI  - Resource-intensive endoscopy: revenue source or cash drain?
AB  - BACKGROUND: Recent research has demonstrated that resource-intensive endoscopic
      procedures are not financially viable if performed without the need for further
      clinical care. OBJECTIVE: To determine whether the net income from downstream
      clinical activities makes resource-intensive endoscopy a financially viable
      activity. DESIGN: Retrospective database review. SETTING: Tertiary-referral
      medical center. PATIENTS: Patients whose initial contacts with the medical center
      were as outpatients who underwent EUS, EMR, or ERCP in 2004. MAIN OUTCOME
      MEASUREMENTS: Hospital charges, the cost of providing services, revenue, and net
      income from all services provided through June 2006. RESULTS: A total of 120
      patients were reviewed whose initial procedure was EUS (48), ERCP (53), or EMR
      (19). Although income was lost by performing the endoscopic procedures, revenue
      was generated by the subsequent clinical care derived from EUS (mean $7093 per
      patient, standard deviation [SD] $23,686, range $12,316-$117,984 per patient); a
      loss of revenue was incurred in the clinical care of both patients who underwent
      ERCP (mean -$5028 per patient, SD $12,565, range -$33,648-$47,481) and patients
      who underwent EMR (mean -$931 per patient, SD $6515, range -$11,245-$12,196). The
      most lucrative activity arising from initial endoscopic referral was surgery.
      Revenue was lost for these procedures in Medicare patients compared with non
      Medicare patients. LIMITATION: Indirect costs are institution specific and may
      not be generalizable to other centers. CONCLUSIONS: EUS is the most remunerative
      resource-intensive endoscopic procedure. Centralizing these resource-intensive
      procedures into multispecialty practice sites that provide surgical and oncologic
      care allows downstream revenue from patient treatment to offset procedural
      losses. Even taking account of downstream revenues, performing these procedures
      on Medicare patients is not financially viable. Any future cuts in Medicare
      physician payment rates will further increase this Medicare/non-Medicare
      reimbursement imbalance and likely have consequences on the performance of these
      procedures.

PMID- 19386306
TI  - Prospective trial comparing solid-state catheter and water-perfusion triple-lumen
      catheter for sphincter of Oddi manometry done at the time of ERCP.
AB  - BACKGROUND: Sphincter of Oddi manometry is the reference standard for the
      diagnosis of sphincter of Oddi dysfunction. Numerous studies have established
      ranges of normal values as well as typical readings in pathologic conditions. All
      these studies have been done using a water-perfused, triple-lumen catheter (TLC).
      A recently approved, new generation, solid-state catheter (SSC) has potential
      advantages, but concerns have been raised as to whether the pressures obtained by
      TLCs are reproducible by SSCs. To date, no data exist on the accuracy of
      sphincter of Oddi pressure measurements with the new-generation SSCs. OBJECTIVE:
      To evaluate the accuracy of the SSC by using the TLC as the reference standard.
      DESIGN: Prospective crossover trial. SETTING: A tertiary academic center.
      PATIENTS: Thirty patients with clinical indications for sphincter of Oddi
      manometry. INTERVENTIONS: Sphincter of Oddi manometry with TLC and SSC in the
      same patient. MAIN OUTCOME MEASUREMENTS: Accuracy of sphincter of Oddi pressure
      measurements. RESULTS: A total of 376 pressure measurements in 47 sphincter
      segments (24 biliary, 23 pancreatic) were obtained. Manometry results were
      abnormal in 10 of 24 biliary sphincters and 12 of 23 pancreatic sphincters. There
      was complete agreement on the final results of the sphincter of Oddi manometry
      (normal/abnormal) between the TLC and SSC (accuracy 100%). A split-plot analysis
      of the 378 individual measurements was performed. The P value of .9966 was
      insignificant, consistent with no catheter effect on the measurements.
      LIMITATIONS: Lack of blinding. CONCLUSIONS: Measurement of sphincter of Oddi
      pressures with the SSC is accurate, and results were essentially identical to
      those of the water-perfused catheter system.

PMID- 19386307
TI  - Prophylactic argon plasma coagulation ablation does not decrease delayed
      postpolypectomy bleeding.
AB  - BACKGROUND: The most common complication of colonoscopic polypectomy is
      postpolypectomy bleeding (PPB). However, there are no established guidelines for
      the prevention of delayed PPB. It is possible that submucosal vessels of an
      artificial ulcer are a potential source of delayed bleeding that occurs several
      days after polypectomy. OBJECTIVE: The aim of this randomized, controlled study
      was to evaluate the efficacy of prophylactic argon plasma coagulation (APC) of
      nonbleeding visible vessels in preventing delayed PPB. DESIGN: A prospective,
      randomized, controlled study. SETTING: A tertiary referral center. PATIENTS: A
      total of 987 polyps in 600 consecutive patients were resected by colonoscopic
      polypectomy. INTERVENTION: In patients who underwent APC (APC group), all
      nonbleeding visible vessels on the ulcer crater were targeted and were then
      coagulated by APC ablation until they disappeared, but not in patients who did
      not undergo APC (control group). MAIN OUTCOME MEASUREMENT: The incidence of
      delayed PPB in the APC group was compared with that in the control group.
      RESULTS: Delayed PPB occurred in 3.3% (16/475) of all the patients, including
      2.5% (6/240) in the APC group and 4.3% (10/235) in the control group. No
      significant differences were observed between the 2 groups in the rates of
      delayed PPB, irrespective of the type of delayed bleeding (significant bleeding:
      0.8% [2/240] vs 1.3% [3/235], P = .638; minor bleeding: 1.7% [4/240] vs 3%
      [7/235], P = .378). There were no significant APC-related complications.
      LIMITATION: Single-center study. CONCLUSION: Prophylactic APC ablation does not
      appear to have an additional advantage in the prevention of delayed PPB.

PMID- 19386308
TI  - Colonic abscess mimicking submucosal tumor.

PMID- 19386309
TI  - Cadaveric assessment of a new guidewire insertion device for volar percutaneous
      fixation of nondisplaced scaphoid fracture.
AB  - PURPOSE: Volar percutaneous screw fixation (PSF) of acute nondisplaced scaphoid
      waist fractures allows early mobilisation of the wrist and a faster return to
      work than prolonged cast immobilisation. Usually, placement of the wire which
      guides the definitive canulated screw is performed by hand. Nevertheless, correct
      placement of this wire is technically difficult. We designed a guidewire
      insertion device (GID) to facilitate this placement. METHODS: We compared the
      hand held technique with the technique using the GID in a cadaveric study. The
      hand held technique was performed on 16 scaphoids and the GID was used in 16
      other scaphoids. The four participating surgeons were divided into two groups:
      two experienced surgeons and two inexperienced surgeons. RESULTS: The GID
      significantly decreased procedure duration (P<0.001), number of attempts to place
      the wire (P<0.001), and number of image-intensifier shots (P<0.001). With both
      techniques, experienced surgeons were significantly faster (P=0.0083) and
      required significantly fewer attempts (P=0.043) than inexperienced surgeons.
      Using the GID, the procedure duration (P=0.0039) and the number of image
      intensifier shots (P<0.001) decreased more with inexperienced surgeons than with
      experienced surgeons. As for the number of attempts, there was no statistical
      difference between the two groups (P=0.32). CONCLUSIONS: The GID decreased the
      time and radiation exposure needed to achieve correct volar percutaneous wire
      placement in the scaphoid, compared to the conventional hand held technique.
      Easier wire placement may lead surgeons to use PSF instead of prolonged cast
      immobilisation for treating nondisplaced scaphoid fractures.

PMID- 19386310
TI  - The Canadian Orthopaedic Trauma Society: a model for success in orthopaedic
      research.
AB  - The Canadian Orthopaedic Trauma Society has been a promoter of multicentre
      research studies for more than a decade. From its modest beginnings, the group
      has grown to over 50 members who meet twice a year. The following article is a
      review of how the group developed to become a leader in level-one orthopaedic
      research. The success of the group stems from the respect and collaboration
      amongst the surgeons and research coordinators. This is most evident in the
      design of new studies. Surgeons and coordinators both have input into new
      protocols and this has been essential in designing protocols that are followed to
      completion. The group has completed a number of prospective randomised trials
      over the years and has received numerous awards. These awards are highlighted
      along with recent publications by the group. These accomplishments have led to
      recognition as a leader in successful randomised orthopaedic trials and have
      helped us to obtain funding for our ongoing and future research.

PMID- 19386311
TI  - Peroxisome proliferator-activated receptor-alpha (PPARalpha): at the crossroads
      of obesity, diabetes and cardiovascular disease.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality world
      wide. The burden of disease is also increasing as a result of the global
      epidemics of diabetes and obesity. Peroxisome proliferator-activated receptor
      alpha (PPARalpha), a member of this nuclear receptor family, has emerged as an
      important player in this scenario, with evidence supporting a central co
      ordinated role in the regulation of fatty acid oxidation, lipid and lipoprotein
      metabolism and inflammatory and vascular responses, all of which would be
      predicted to reduce atherosclerotic risk. Additionally, the Fenofibrate
      Intervention and Event Lowering in Diabetes (FIELD) study has indicated the
      possibility of preventive effects in diabetes-related microvascular
      complications, although the mechanisms of these effects warrant further study.
      The multimodal pharmacological profile of PPARalpha has prompted development of
      selective PPAR modulators (SPPARMs) to maximise therapeutic potential. It is
      anticipated that PPARalpha will continue to have important clinical application
      in addressing the major challenge of cardiometabolic risk associated with type 2
      diabetes, obesity and metabolic syndrome.

PMID- 19386312
TI  - Mechanical events within the arterial wall: The dynamic context for elastin
      fatigue.
AB  - Change in arterial stiffness is generally considered a risk factor for
      cardiovascular disease and, in various ways, has been associated with
      hypertension, diabetes, hyperlipidemia, atherosclerosis, and heart failure,
      likely because of altered dynamics of the wall and of the fluid-wall interplay in
      pulsatile flow. We present a comprehensive analytical study of longitudinal
      displacements and stresses within the thickness of the vessel wall induced by
      pulsatile flow at different times within the cardiac cycle, using the fractional
      derivative model which has been found to provide a good descriptor of the
      rheological material's response to frequency. The results indicate that the
      extent of displacement and shear stress within the depth of the vessel wall
      depend critically on the degree to which the wall is tethered to surrounding
      tissue and on the mechanical consistency of the wall material, particularly on
      the relative proportions of viscous and elastic content within the wall. In
      particular, loss of viscous consistency leads to higher shear stresses within the
      wall thus putting higher loading on elastin and may ultimately lead to elastin
      fatigue and, as elastin gradually fails, its load bearing function is presumably
      taken over by collagen which renders the vessel wall less elastic and more rigid
      as is indeed observed in the aging process. It is thus concluded that loss of
      viscous content within the vessel wall, whether by disease or aging, may be a
      prelude to elastin fatigue and elastin failure within the vessel wall.

PMID- 19386313
TI  - Effects of excessive body weight on postural control.
AB  - Research that evaluated both static and dynamic stability was performed, to
      clarify the impact of excessive body weight on postural control. The spontaneous
      center of foot pressure (CP) motion during quiet stance and a range of forward
      voluntary CP displacements were studied in 100 obese, and 33 lean women.
      Characteristics of postural sway were acquired while the subjects were standing
      quiet on a force plate with eyes open (EO) and with eyes closed (EC). Their
      anterior range of CP voluntary displacements was assessed upon a range of maximal
      whole body leanings which were directed forward. A substantial reduction of
      postural sway was observed in all patients which had increased body weight. Main
      postural sway parameters i.e., the total path length as well as its directional
      components were negatively correlated with the body mass and body mass index
      (BMI). The range of a whole body voluntary forward leaning, did not exhibit any
      significant change in patients with an obesity grade of I and II. Such a deficit
      was, however, found in subjects with a body mass index above 40. In conclusion,
      the increased body weight imposed new biomechanical constraints, that resulted in
      functional adaptation of the control of the erect posture. This functional
      adaptation was characterized by a reduced postural sway associated with a
      substantial reduction of the dynamic stability range in subjects with BMI>40.

PMID- 19386314
TI  - Analysis of phytosterols in extra-virgin olive oil by nano-liquid chromatography.
AB  - In this work the applicability of nano-liquid chromatography (nano-LC) was
      evaluated for the determination of phytosterols in extra-virgin olive oil
      samples. These compounds represent a minor part of lipids in vegetable oils, but
      their quantification can be useful to establish oil origin and to reveal
      intentional adulterations. The analysis of five main sterols, specifically
      brassicasterol, stigmasterol, campesterol, cholesterol and beta-sitosterol, was
      performed in a laboratory-assembled nano-LC system coupled with a UV detector.
      The separation of all compounds was obtained in about 20 min, employing a
      capillary column packed with a C18-RP (sub-2 microm particles) stationary phase
      for 15 cm. Methanol only was used as mobile phase. The simple method developed
      and optimized was validated in terms of repeatability, linearity, limit of
      detection and limit of quantification (0.78 and 1.56 microg/mL, respectively)
      achieving good results. After this, it was applied to the determination of
      phytosterols in extra-virgin olive oil samples. Isolation of phytosterols was
      obtained by solid-phase extraction, after saponification and liquid-liquid
      extraction of the unsaponified fraction with diethyl ether. Recovery tests were
      performed and values between 90% and 103%, with RSDs within 5%, were obtained.
      Moreover the nano-LC system was coupled with a mass spectrometer for an accurate
      identification of phytosterols.

PMID- 19386315
TI  - Lamp-based native fluorescence detection of proteins in capillary
      electrophoresis.
AB  - The potential of a recently developed lamp-based fluorescence detector for the
      analysis of underivatised proteins by capillary electrophoresis (CE) was
      investigated. Fluorescence detection (Flu) was achieved using optical light
      guides to deliver excitation light from a Xenon-Mercury lamp to the capillary
      detection window and to collect fluorescence emission and lead it to a
      photomultiplier. The performance of the detector was evaluated by monitoring the
      native fluorescence of the amino acid tryptophan and the proteins alpha
      chymotrypsinogen A, carbonic anhydrase II, lysozyme and trypsinogen upon
      excitation at 280 nm. The test compounds were analysed using background
      electrolytes (BGEs) of sodium phosphate at pH 3.0 and 11.3. The results were
      compared to experiments of CE with UV absorbance detection. For tryptophan, a
      linear fluorescence response was obtained with a dynamic range of over 4 orders
      of magnitude, and a limit of detection (LOD) of 6.7nM. This LOD was a factor of
      200 more favourable than UV detection at 280 nm, and a factor of 20 better than
      detection at low-UV wavelengths. All tested proteins showed linear fluorescence
      responses up to 250 microg/mL. LODs were typically in the 10-20 nM range. These
      LODs were a factor of 25 lower than for UV detection at 280 nm, and comparable to
      UV detection at low-UV wavelengths. Overall, Flu yields much more stable
      baselines, especially with a BGE of high pH. The applicability of CE-Flu is
      demonstrated by the analysis of a degraded protein mixture, and of an expired
      formulation of the protein drug human growth hormone, indicating that protein
      degradation products can be selectively detected.

PMID- 19386316
TI  - Hydrothermal preparation and photocatalytic activity of mesoporous Au-TiO2
      nanocomposite microspheres.
AB  - Au-TiO2 nanocomposite microspheres were prepared by hydrothermal treatment of
      precipitates of tetrabutyl titanate (Ti(OC4H9)4) in a mixed solution of water,
      ethanol and Au colloid particles at 180 degrees C for 7 h. The as-prepared
      products were characterized by scanning electron microscopy, transmission
      electron microscopy, X-ray diffraction, nitrogen sorption, UV-visible diffuse
      reflectance spectroscopy, X-ray photoelectron spectroscopy and photoluminescence
      spectroscopy. The photocatalytic activity was evaluated by photocatalytic
      oxidation decomposition of formaldehyde in air. The results showed that the
      presence of nanosized Au particles slightly depressed the grain growth of
      anatase, resulting in smaller crystallite size and greater specific surface
      areas. Moreover, the absorbance and photoluminescence of anatase TiO2 was
      modified by those added Au nanoparticles and an appropriate Au amount in Au-TiO2
      nanocomposite microspheres led to increase of band gap, decrease of
      photoluminescence intensity and prolongation of life of photo-generated electrons
      and holes. The photocatalytic activity of Au-TiO2 nanocomposite microspheres was
      obviously higher than that of pure TiO2 microspheres and Degussa P25. When the
      atomic percentage ratio of Au to Ti was below 0.00425, the apparent reaction rate
      constants increased. When the atomic percentage ratio of Au to Ti reached
      0.00425, the sample displayed the highest photocatalytic activity.

PMID- 19386317
TI  - Simulation and experimental study of intercalation of urea in kaolinite.
AB  - Experimental measurements and molecular simulations were used to describe the
      characteristics of the kaolinite/urea intercalation compound. The intercalation
      compound was synthesized by a mechanochemical method and examined by X-ray
      diffraction and thermogravimetry. Additionally, a series of NpT (constant
      particle number-pressure-temperature) simulations was performed to identify
      thermodynamically stable basal spacings. From the simulations the most probable
      molecular orientations were determined for single and double layered arrangements
      of urea molecules that develop between the layers of kaolinite.

PMID- 19386318
TI  - Are self-explanations always beneficial?
AB  - We present evidence suggesting that the effect of self-explanations on learning
      is not always beneficial and, in fact, in some contexts has a detrimental effect.
      Over eight sessions, fourth-graders engaged in investigation of a database with
      the goal of identifying causal effects. In a separate task, children in one
      condition also generated self-explanations regarding the mechanisms underlying
      the causal effects they believed to be present. In a comparison condition, they
      did not. On a transfer task, children in the no-explanations condition showed
      superior causal inference performance. The findings are discussed as reflecting
      the development of "data-reading" skill with which an emphasis on explanations
      may interfere.

PMID- 19386319
TI  - A sensitive, noise-resistant method for identifying focal demyelination and
      remyelination in patients with multiple sclerosis via voxel-wise changes in
      magnetization transfer ratio.
AB  - Magnetization transfer imaging (MTI) provides a reliable and histopathologically
      validated means for identifying important tissue changes in multiple sclerosis
      (MS), including demyelination and remyelination. However, most approaches to date
      have been based on a priori regions of interest (ROIs) and have been relatively
      insensitive to small focal changes or competing processes. More recent techniques
      have sought to address this through a voxel-wise approach, but have been limited
      in their detection capabilities by the amount of noise in standard MTR images. To
      address this issue while remaining sensitive to local changes, we propose the use
      of the recently introduced threshold-free cluster enhancement (TFCE) technique in
      combination with a Monte Carlo estimation approach. TFCE is first applied to
      enhance individual voxels based on their level of local cluster support, and then
      Monte Carlo estimation is performed to allow meaningful statistical
      interpretation of the resulting TFCE values. We validated this technique in three
      complementary ways: healthy control scan-rescan analysis, analysis of a "gold
      standard" simulated dataset, and analysis of a group of MS patients and healthy
      volunteers with 1-year longitudinal MRI scans. Scan-rescan analysis demonstrated
      a very low false-positive rate (1.44 mL increasing and 1.48 mL decreasing at the
      optimal detection threshold). Simulated dataset analysis yielded an area under
      receiver-operating characteristic curve of 0.942 (compared to 0.801 for a more
      conventional voxel-wise thresholding analysis). Finally, analysis of the real
      subject population showed highly significant differences (p<0.001) in volume of
      decreasing MTR between patients and controls. The proposed method provides a
      valuable means for quantifying MS-related tissue changes, particularly
      demyelination and remyelination, in vivo and without the use of highly complex or
      experimental MRI acquisition techniques. It improves on the sensitivity of other
      approaches, and may increase the statistical power of studies investigating the
      effects of therapy on MRI outcomes in MS.

PMID- 19386320
TI  - Nematode response to metal, PAHs and organic enrichment in tourist marinas of the
      Mediterranean Sea.
AB  - The structure of nematode assemblages was investigated in the sediments of two
      different tourist marinas in the Mediterranean Sea and related to pollution
      variables. Nematode densities and generic compositions were determined, as were
      concentrations of heavy metals, PAHs and organic matter. Results showed different
      assemblages at the two marinas, with a dominance of the genera
      Paralongicyatholaimus and Daptonema. Significant correlations between nematodes
      and concentrations of environmental contaminants were found. In particular,
      Paralongicyatholaimus showed a significant negative correlation with Cu
      concentrations and was almost absent at the stations where higher Cu
      concentrations were found. The presence of sensitive/tolerant nematode genera
      represents a promising tool to identify areas subjected to a higher level of
      disturbance and to define the correct environmental management strategy for
      harbors.

PMID- 19386321
TI  - [Preclinical atherosclerosis in a group of young subjects with type 1 diabetes
      from a Mediterranean area].
AB  - BACKGROUND AND OBJECTIVE: Carotid intima-media thickness (cIMT) and presence of
      atherosclerotic plaques were evaluated in a cross-sectional study performed in a
      group of type 1 diabetes mellitus (T1D) subjects from a Mediterranean area
      without additional cardiovascular risk factors. These results were compared to
      those obtained from a reference population. PATIENTS AND METHODS: Twenty-two
      patients with T1D (age 34.6 (7.9) years) and a disease duration of 15.3 (5.9)
      years) were included. B-mode IMT measurements were used to evaluate cIMT and the
      presence of plaques. RESULTS: A significantly higher cIMT and max-cIMT were found
      in patients with T1D in comparison with the age-reference population (0.52 (0.08)
      vs. 0.46 (0.09)mm; p<0.001 and 0.63 (0.13) vs. 0.55 (0.12); p<0.007 for cIMT and
      max-cIMT, respectively). The proportion of subjects affected by plaques within
      the group of T1D subjects was equivalent to the value observed in the 46-55 year
      old reference group. CONCLUSION: Even in the absence of major cardiovascular risk
      factors, subjects with T1D from a low prevalence CVD risk area display signs of
      an increased and accelerated preclinical atherosclerotic process.

PMID- 19386322
TI  - [Lipoprotein (a), D-Dimer and apolipoprotein A1 as markers of presence and
      severity of coronary disease].
AB  - BACKGROUND AND OBJECTIVE: To examine the relationship between blood levels of
      lipids as well as haemostatic and inflammatory markers and the presence and
      severity of angiographically-evaluated coronary stenosis. MATERIAL AND METHOD: We
      included 897 patients (629 males and 268 females), aged 65.12+/-11.23 years, who
      were admitted to the hospital presenting an acute episode or to discard coronary
      heart disease. Each patient underwent coronariography using the Seldinger
      technique. Blood samples were drawn to analyze lipid [total cholesterol,
      HDLcholesterol, triglycerides, LDLcholesterol, apolipoprotein A1, apolipoprotein
      B100, lipoprotein (a)], haemostatic (fibrinogen, D-Dimer, tissue factor and
      tissue factor pathway inhibitor), and inflammatory (C-reactive protein, leukocyte
      count) markers. RESULTS: Six hundred and fifty nine patients presented coronary
      stenosis and 238 were considered as controls. Patients with coronary stenosis
      presented higher values of lipoprotein (a), D-Dimer, C-reactive protein and
      leukocyte count and lower concentrations of HDLcholesterol, apolipoprotein A1 and
      total cholesterol than controls. In a multivariate analysis, sex (OR 2,692; IC95%
      1,822-3,979), dislypemia (OR 2,241; IC95% 1,559-3,221), arterial hypertension (OR
      1,623; IC95% 1,116-2,359), diabetes (OR 1,608; IC95%1,054-2,451), leukocyte count
      (OR 1,181; IC95% 1,082-1,288), lipoprotein (a) (OR 1,205 IC95% 1,079-1,346), D
      dimer (OR 1,468 IC95% 1,152-1,871) and apolipoprotein A1 (OR 0,992 IC95% 0,985
      0,999) were independent risk factors of coronary obstruction. Only lipoprotein
      (a) and D-dimer levels increased according to the severity of obstruction whereas
      apolipoprotein A1 and HDl cholesterol diminished. CONCLUSIONS: Our results
      suggest that lipoprotein (a), D-dimer and apolipoprotein A1 are significantly
      associated with the presence and severity of coronary stenosis.

PMID- 19386323
TI  - [Seroprevalence study of hepatitis B among orienteers].
AB  - BACKGROUND AND OBJECTIVE: Our objectives were to detect asymptomatic cases
      involved in an outbreak of hepatitis B, to assess the seroprevalence of hepatitis
      B (HB) in orienteers and to establish recommendations. PATIENTS AND METHOD: One
      hundred sixteen orienteers who had competed in the categories involved in the
      previous outbreak as well as a stratified random sample of 166 of the remaining
      orienteers in other competition categories were included in a cross-sectional
      serological prevalence study. HB surface antigen (anti-HBs); total antibody to HB
      core antigen (total anti-HBc); HB surface antigen (Ag HBs); and antibody IgM to
      HB core antigen (anti-HBcIgM) along with the history of vaccination for hepatitis
      B were analyzed. The results were weighted. RESULTS: The seroprevalence of HB
      (total anti-HBc positive) was 6.7% (n=12, 95% CI 0.6-12.9). No case of acute HB
      or chronic infection was observed. All the serological markers were negative for
      61.1% (n=64, 95% CI 46.3-75.6), and 31.5% (n=29, 95% CI 18.2-46.4) had markers of
      immunity due to vaccination. Among individuals under 25 years of age, 28.4% were
      unvaccinated, although they were covered by vaccination programs. CONCLUSION: Our
      results suggest that the seroprevalence of HB among orienteers is not different
      from the general population in Spain. However, it is necessary to reinforce the
      vaccination among adolescents and young adults. General recommendations for the
      prevention of HB were made to orienteering federations.

PMID- 19386324
TI  - [Clinicopathological cases: a great chance for continuous learning].

PMID- 19386325
TI  - [Outpatient treatment of venous throemboembolic disease].
AB  - The advent of subcutaneous treatment with low -molecular-weight heparins (LMWH)
      and less intensive monitoring has made it possible for patients the treatment at
      home. Large, randomised, controlled trials have demonstrated that outpatient
      treatment of deep vein thrombosis (DVT) with LMWH is as safe as the hospital
      based treatment with intravenous unfractionated heparin (UFH). However, the risk
      of death in patients with treatment at home is higher for pulmonary embolism (PE)
      than for DVT, and additional evidence is required before the results of
      outpatient treatment for DVT can be extrapolated to PE. The prognostic
      stratification of patients with acute PE has important management implications
      for the outpatient treatment.

PMID- 19386326
TI  - [Postural control disorders in initial phases of whiplash].
AB  - BACKGROUND AND OBJECTIVE: Dizziness of variable intensity is a frequent complaint
      in patients who suffered whiplash and largely documented balance disturbances.
      The objective of the study was to identify balance disorders in early stage of
      whiplash after road traffic accidents. PATIENTS AND METHOD: Ninety nine women
      were included in the study. Fifty four women had suffered whiplash within two
      weeks and 45 were included in a healthy control group. Static posturography on a
      force platform was carried out in all study participants, by means of the Romberg
      test in four sequential phases, using the postural sway area (SA) as a dependent
      variable. Visual Analogic Scale (VAS) and Northwick Park Neck Pain Questionnaire
      (NPH) were used to evaluate pain and function. RESULTS: Postural sway area
      increased significantly in each of the consecutive phases in both groups. The
      differences of the means of the postural sway area were statistically significant
      in all Romberg phases (p=.009 to P=.000). No correlation was found between SA and
      VAS or NPH scores. There was a positive correlation between the postural sway
      area standing on a thick foam cushion placed over the plate with closed eyes and
      the number of days of transitory incapacity (r=0.414; P=.009). CONCLUSIONS:
      Patients with recent whiplash show a postural control disturbance revealed trough
      a sequential static posturography analysis. This suggests that the balance
      disorder is not only a consequence of late whiplash syndrome evolution.
      Therefore, we should promote early instauration of a specific therapeutic
      approach if and when the patient refers dizziness and related symptoms.

PMID- 19386327
TI  - [Clinical study of 28 patients with cerebellar hemorrhage].
AB  - BACKGROUND AND OBJECTIVE: To characterize the clinical features, etiology and
      prognosis of cerebellar hemorrhage. PATIENTS AND METHODS: Descriptive study of 28
      patients with cerebellar hemorrhages included in the Sagrat Cor Hospital of
      Barcelona Stroke Registry over a 19 year period. The vascular risk factors and
      clinical profiles in the subcortical hemorrhage group (n=133) were compared.
      RESULTS: Cerebellar hemorrhages accounted for 0.73% of all acute strokes
      (n=3,808) and 6,9% of all intracerebral hemorrhages. Hypertension was present in
      60,7%, atrial fibrillation in 17,9% and ischemic heart disease in 10,4%. The
      overall in-hospital mortality rate was 21,4%. Ataxia (OR=91,75; 95% CI, 14,90
      564,98), nausea and vomiting (OR=12,85; 95% CI, 2,80-58,93) and sensory symptoms
      (OR=0.05; 95% CI, 0,01-0,36) were independent clinical predictors related to
      cerebellar hemorrhage. CONCLUSIONS: Cerebellar hemorrhage is uncommon. In
      hospital mortality is 21.4% and clinical profiles were different in cerebellar
      hemorrhages when compared to subcortical hemorrhages.

PMID- 19386328
TI  - [Uneasiness or uncomfortably: is it a symptom ovenproof in the end of life?].

PMID- 19386329
TI  - [A 24 year-old man with fever and cutaneous rash].

PMID- 19386330
TI  - ["New" cardiovascular risk factors: will they emerge or will go down?].

PMID- 19386331
TI  - [Usefulness of anaerobic vial in the diagnosis of bacteremia or fungemia].

PMID- 19386332
TI  - [Mediterranean environment and protection on the cardiovascular risk of type 1
      diabetes].

PMID- 19386333
TI  - [Thyroid dysfunction in patients with pulmonary arterial hypertension. A cohort
      study of 58 patients].
AB  - BACKGROUND AND OBJECTIVE: Thyroid disease (TD) is more prevalent in patients with
      pulmonary arterial hypertension (PAH) than in the general population. The
      frequency and the cause of this association are not well established. We aimed to
      quantify and analyze the incidence and characteristics of TD in a cohort of PAH
      patients (idiopathic or preferentially associated with systemic diseases) and
      review the literature. PATIENTS AND METHOD: Fifty eight PAH patients were
      prospectively studied, according to a previously established protocol (that
      included right heart catheterization); TSH, T(4), and antithyroglobulin and
      antiperoxidase antibodies were determined. TD was defined as an abnormal TSH
      level and/or elevated antithyroid antibodies (TAbs). Clinical, biological and
      hemodynamic variables were compared between patients with and without TD.
      RESULTS: TD was detected in 30 patients (51%): high TSH levels were observed in
      21 (36,21%); hyperthyroidism in 2 (3,45%); and TAbs in 16 of 54 (27,59%), 7 of
      whom were euthyroid. In the TD group, PAH evolution time was longer (4,62 vs 2,61
      years; P=.005, CI 95%, 0,63-3,38), more patients were in functional class IV
      (13;43,3% vs 5;15,8%, P=.046, CI 95% ,0,05-11,75), cardiac output was lower
      (P=.032, CI 95%, 3,16-4,89) and epoprostenol treatment was more frequently used
      (14;46,6% vs 4;14,3%, P=.008, CI 95%, 1,46-18,85; OR=5,25). CONCLUSIONS: The
      frequency of TD detected in this PAH cohort reaches 51% and it was associated
      with a longer evolution time of PAH and worse hemodynamic situation. Although
      epoprostenol was used more frequently in TD patients, a causal relationship with
      TD could not be established.

PMID- 19386334
TI  - A province-based surveillance system for the risk factors of non-communicable
      diseases: A prototype for integration of risk factor surveillance into primary
      healthcare systems of developing countries.
AB  - OBJECTIVES: To establish a surveillance system for risk factors of non
      communicable diseases, develop a valid tool and methodology for surveillance
      surveys, and build capacity in 41 provincial surveillance sites to design and
      conduct the surveys and provide provincially interpretable baseline data. STUDY
      DESIGN: Population-based national study. METHODS: The World Health Organization's
      STEPwise approach to non-communicable disease surveillance was adapted to design
      a national risk factor surveillance model. The first national population-based
      and cross-sectional study was conducted in 2005 in 41 universities of medical
      sciences in all 30 provinces of Iran. This involved multi-stage cluster sampling
      from 25-64 year-old Iranians and non-institutionalized populations. A national
      technical unit at the Ministry of Health and Medical Education supervised all
      study processes including data management and analysis. RESULTS: From the
      national results, the survey estimated that the prevalence of daily current
      smoking was 17.9%. Of the target population, 5% consumed at least five combined
      servings of fruit and vegetables per day. The median daily time spent undertaking
      transport-related physical activity (43.8 min) was significantly higher than the
      median time spent on work-related physical activity (27.5 min) or recreational
      physical activity (28.6 min). Overall, 54.7% of the target population were
      overweight or obese, and waist circumference was greater among women than men.
      The prevalence of hypertension was 23.8%, with a higher prevalence among women
      than men. In addition, 6% of the target population had a high fasting blood
      glucose (> or =126 mg/dl), and 45.1% had a total cholesterol level of at least
      200 mg/dl. CONCLUSION: Integration of province-based surveillance activities into
      the Iranian primary healthcare system is feasible. Provincial reports could
      provide a baseline picture of the most important risk factors for non
      communicable diseases. There are several important risks with a prominent burden
      that may cause a progressive epidemic of major non-communicable diseases in the
      future in the absence of quality interventions.

PMID- 19386335
TI  - Health impact assessment: the contribution of the right to the highest attainable
      standard of health.
AB  - There are growing demands for governments to carry out human rights impact
      assessments prior to adopting and implementing policies. This article outlines a
      preliminary human rights impact assessment methodology, using the right to the
      highest attainable standard of health as the case study. The authors recommend a
      mainstreaming approach, which involves integrating human rights into existing
      impact assessment methodologies. Accordingly, they identify considerations that,
      from a human rights perspective, governments should incorporate into existing
      impact assessment methodologies in order to comply with their legal obligations
      to realize human rights. To test the mainstreaming methodology, the authors
      propose integrating the right to the highest attainable standard of health into
      health impact assessment.

PMID- 19386336
TI  - Assessment of six different collagenase-based methods to isolate feline
      pancreatic islets.
AB  - Isolation of pancreatic islets is necessary to study the molecular mechanisms
      underlying beta-cell demise in diabetic cats. Six collagenase-based methods of
      isolation were compared in 10 cat pancreata, including single and double course
      of collagenase, followed or not by Ficoll centrifugation or accutase, and
      collagenase plus accutase. Morphometric analysis was performed to measure the
      relative area of islet and exocrine tissue. Islet specific mRNA transcripts were
      quantified in isolates by real-time PCR. The single and double course of
      collagenase digestion was successful in each cat and provided similar islet-to
      exocrine tissue ratio. Quantities of insulin mRNA did not differ between the two
      methods. However, on histological examination either method yielded only
      approximately 2% of pure islets. The other methods provided disrupted islets or
      insufficient samples in 1-7 cats. Although pancreas digestion with single and
      double course of collagenase was superior, further studies are needed to improve
      islet isolation in cats.

PMID- 19386337
TI  - Gene delivery to renal tubular epithelial cells using adeno-associated virus
      vector in domestic cats.
AB  - Recombinant adeno-associated virus (rAAV) vectors provide excellent gene delivery
      into the kidney in several mammals. This study evaluated gene delivery into the
      cat kidney using an rAAV vector. First, infection and reporter gene expression
      using rAAV vector encoding the enhanced green fluorescent protein gene (rAAV
      EGFP) was examined in vitro in epithelial crandell reese feline kidney (CRFK)
      cells. At 12h after transduction, green fluorescence was detected in cells. Next,
      the rAAV-EGFP construct was injected into the kidneys of two anesthetized cats
      via the skin, similar to a renal biopsy. On 3 and 12days after injection, green
      fluorescence was detected in renal tubules localized near the injected site, but
      not in glomeruli, blood vessels, or interstitial cells. Finally, the rAAV-EGFP
      construct was transduced into kidney sections cultured ex vivo. EGFP was
      expressed in renal tubules between the outer cortex and inner medulla regions.
      These results demonstrate that rAAV vectors effectively mediate gene delivery
      into cat renal tubules, and may prove usefulness in gene therapy for cats with
      renal diseases.

PMID- 19386338
TI  - [MRI features of spinal neurosarcoidosis associed with cervical spondylosis].
AB  - INTRODUCTION: Spinal neurosarcoidosis is rare and exceptionally inaugural.
      OBSERVATION: A 49-year-old African woman developed a progressive left Brown
      Sequard syndrome. Magnetic resonance imaging (MRI) scans of the cervical spinal
      cord revealed an intramedullary lesion from C2 to T1 with intense pial
      enhancement after administration of contrast material associated with cervical
      spondylosis. The diagnostic of sarcoidosis was confirmed by liver biopsy which
      demonstrated noncaseating granulomas. CONCLUSIONS: MRI features of spinal
      neurosarcoidosis were reviewed by the authors with focus on differential
      diagnosis.

PMID- 19386339
TI  - Lymphopenia is observed regularly in the acute (leptospiraemic) phase but not the
      immune phase of leptospirosis.
AB  - Lymphocyte counts in patients with leptospirosis have been shown to be variable.
      This study retrospectively compared lymphocyte counts from the first blood
      samples taken following hospital presentation in patients with leptospirosis who
      were either (i) IgM non-reactive, (ii) IgM reactive and microscopic agglutination
      test (MAT) non-reactive or (iii) IgM and MAT reactive in an effort to determine
      whether differences in lymphocyte counts are observed in the acute and immune
      phase of leptospirosis. Statistical differences in lymphocyte counts were
      observed between the three groups. In conclusion, this study has shown that the
      phase of leptospiral infection may affect patient lymphocyte counts.

PMID- 19386340
TI  - Estimating the kinetic parameters of activated sludge storage using weighted non
      linear least-squares and accelerating genetic algorithm.
AB  - In this study, weighted non-linear least-squares analysis and accelerating
      genetic algorithm are integrated to estimate the kinetic parameters of substrate
      consumption and storage product formation of activated sludge. A storage product
      formation equation is developed and used to construct the objective function for
      the determination of its production kinetics. The weighted least-squares analysis
      is employed to calculate the differences in the storage product concentration
      between the model predictions and the experimental data as the sum of squared
      weighted errors. The kinetic parameters for the substrate consumption and the
      storage product formation are estimated to be the maximum heterotrophic growth
      rate of 0.121/h, the yield coefficient of 0.44 mg CODX/mg CODS (COD, chemical
      oxygen demand) and the substrate half saturation constant of 16.9 mg/L,
      respectively, by minimizing the objective function using a real-coding-based
      accelerating genetic algorithm. Also, the fraction of substrate electrons
      diverted to the storage product formation is estimated to be 0.43 mg CODSTO/mg
      CODS. The validity of our approach is confirmed by the results of independent
      tests and the kinetic parameter values reported in literature, suggesting that
      this approach could be useful to evaluate the product formation kinetics of mixed
      cultures like activated sludge. More importantly, as this integrated approach
      could estimate the kinetic parameters rapidly and accurately, it could be applied
      to other biological processes.

PMID- 19386341
TI  - Computational modelling to investigate the sampling of lead in drinking water.
AB  - The monitoring of lead in drinking water is beset by difficulties relating to the
      inherent temporal variation of lead emissions at individual premises. Such
      difficulties are compounded by spatial variation when considering an entire water
      supply area (e.g., City or Town), which is necessary to determine compliance with
      regulatory standards and to judge the efficacy of corrective measures. A
      computational modelling system, that uses a Monte Carlo probabilistic framework
      for simulating lead emissions within a water supply area, has been successfully
      validated in a range of UK case studies and enabled corrective treatment measures
      to be optimised for a range of water types. This modelling system includes the
      simulation of a range of sampling methods, and has made it possible to undertake
      an exhaustive comparison between daily average lead emissions (DAC--which are
      equivalent to weekly average lead concentrations as a consequence of the
      modelling system used), random daytime sampling (RDT), 30 min stagnation sampling
      (30MS) and 6 h stagnation sampling (6HS). It is concluded that: (a) the
      stringency of UK and US compliance assessment methods for lead in drinking water
      is fairly similar for waters of reduced plumbosolvency, despite different
      sampling approaches; (b) RDT sampling is equivalent to random DAC for waters of
      moderate plumbosolvency; (c) RDT sampling is more stringent than random DAC for
      waters of low plumbosolvency; (d) all random sampling methods suffer from poor
      reproducibility, albeit less so for low plumbosolvency water; and (e) fixed point
      stagnation sampling may not be representative.

PMID- 19386342
TI  - Sociodemographic factors influencing participation in the Barcelona Health Survey
      study on serum concentrations of persistent organic pollutants.
AB  - BACKGROUND: Little is known about factors affecting participation in population
      based biomonitoring studies. We analyzed socioeconomic factors influencing
      participation in the Barcelona Health Survey (BHS) study on the distribution of
      serum concentrations of persistent organic pollutants (POPs). METHODS: After
      completing the BHS personal interview at home participants aged >or=15 years were
      invited to donate blood. Conducted on a different date and location, the POPs
      study included additional questions, blood extraction, and a brief physical
      examination. Factors influencing participation were analyzed by logistic
      regression. RESULTS: Of 523 BHS participants that we contacted to participate in
      the study, 231 (44%) participated; they were broadly representative of the city
      population regarding sex, birth place, body mass index (BMI), employment status
      and occupational social class. Participants in the POPs study had higher
      educational level and family income. Controlling for confounders, participation
      was slightly higher among women than men (odds ratio [OR]=1.38, p=0.02), and
      lower among the youngest and oldest subjects (p=0.002), with a strong and
      monotonic trend of increasing participation with increasing educational level
      (p<0.001) (OR for university level vs. no studies=4.58, 95% CI: 2.3-9.3).
      CONCLUSIONS: Although participation was somewhat low, participants were similar
      to the city population regarding sex, BMI, birth place, employment, and
      occupational social class. Health surveys that integrate environmental biomarkers
      should invest specific resources to encourage participation of the youngest and
      oldest individuals, and of those with more disadvantaged socioeconomic position
      (particularly, citizens with lowest education).

PMID- 19386343
TI  - Bioassay-directed fractionation of marine sediment solvent extracts from the east
      coast of Ireland.
AB  - Crude solvent extracts were prepared from three sediment sites in Ireland namely
      Bull Lagoon, Dunmore East and Dublin Port. These were assayed with Tisbe
      battagliai and the Microtox system. The extracts were chemically characterised
      using a variety of analytical techniques for a suite of organic contaminants.
      Metals and organic contaminant concentration data are reported for the three
      sites. On the basis of determined toxicity and chemical analysis of these crude
      extracts, a further bioassay-directed fractionation (BDF) employing the Dunmore
      East crude organic extract was conducted in addition to chemical analysis. For
      the crude extracts, T. battagliai and Microtox system demonstrated an order of
      decreasing toxicity for each of the three sites to be Dublin Port>Dunmore
      East>Bull Lagoon. Microtox system EC10 values after 30min exposure were 1.08%,
      11.6% and 26.9% solvent extract for these sites, respectively. Fractionation of
      the Dunmore East extract revealed that fraction 1 was the most toxic fraction to
      both the T. battagliai and the Microtox system demonstrating EC50's after 48 h
      and 30 min of 44.7% and 16.8% solvent extract for the T. battagliai and Microtox
      assays, respectively. T. battagliai however did show increased sensitivity to
      fraction 3 when comparing EC10 values and demonstrated an EC10 value of 17.8%
      solvent extract after 48h. Fraction 1 was shown to contain the highest quantity
      of the butyltins, in particular TBT in relation to fractions 2 and 3. A useful
      BDF technique was developed and employed in this study.

PMID- 19386344
TI  - Influence of soil properties on the biodegradation of 1,3,6,8-tetrachlorodibenzo
      p-dioxin and fungal treatment of contaminated paddy soil by white rot fungus
      Phlebia brevispora.
AB  - To examine the bioremediation potential of Phlebia brevispora in dioxin
      contaminated soil, the fungus was inoculated into autoclaved soil that was
      contaminated with 2,7-dichlorodibenzo-p-dioxin (2,7-DCDD) or 1,3,6,8
      tetrachlorodibenzo-p-dioxin (1,3,6,8-TCDD). Three types of soils, organic-rich
      soil (Andosol), organic-poor soil (Granitic Regosols), and paddy soil, were used
      for the construction of artificially contaminated soil to understand the
      influence of the soil property on fungal growth and dioxin degradation ability.
      Under a solid-state condition, although the growth of the fungus improved in
      organic-rich soil, the degradation of 2,7-DCDD was inhibited. Although the
      degradation of 1,3,6,8-TCDD under a solid-state condition was inhibited severely,
      1,3,6,8-TCDD degradation was observed under a slurry-state condition in organic
      poor soil. In the case of organic-rich soil, an increase in water content
      improved the 1,3,6,8-TCDD degradation efficiency. When the historically
      contaminated paddy soil was treated with P. brevispora under a slurry-state
      condition, 1,3,6,8-TCDD as the main contaminant degraded 50% after 90d
      incubation.

PMID- 19386345
TI  - Expression patterns of Trk-A, Trk-B, GRP78, and p75NRT in olfactory
      neuroblastoma.
AB  - Olfactory neuroblastoma is an uncommon neuroectodermal tumor of the sinonasal
      tract. It represents 2% to 3% of sinonasal neoplasms. Most olfactory
      neuroblastoma behave locally aggressive with 30% recurrence rates. A subset
      metastasizes to lymph nodes and/or distant sites. Grading of olfactory
      neuroblastoma involves a combination of factors with low-grade tumors having
      better survival than high-grade tumors. The grade does not always predict
      prognosis, however, as metastases can be seen in all grades of olfactory
      neuroblastoma. Trk-A, Trk-B, and p75NRT are neurotrophin receptors associated
      with numerous solid malignancies, particularly pediatric neuroblastoma. GRP78 is
      an endoplasmic reticulum protein, associated with differentiation of neuroblastic
      cells. Trk-A, p75NRT, and GRP78 overexpression are favorable prognostic factors
      in pediatric neuroblastoma, whereas Trk-B is associated with a poorer prognosis
      in these tumors. Olfactory neuroblastoma is clinically distinct from pediatric
      neuroblastoma but shares some histological features. Trk-A and p75NRT have been
      demonstrated in olfactory neuroblastoma previously. Trk-B and GRP78 have not been
      investigated in olfactory neuroblastoma. None of these markers have been
      correlated with grade or outcome in olfactory neuroblastoma. To investigate the
      role of Trk-A, Trk-B, p75NRT, and GRP78, a series of 20 olfactory neuroblastomas
      was stained with these antibodies. Trk-A and Trk-B stained most cases of
      olfactory neuroblastoma (90% and 85%). GRP78 stained most cases (90%), although
      weakly. P75NRT demonstrated focal membranous staining in a sustentacular pattern
      (60%). None of these markers correlated with Hyams grade. None of these markers
      definitively correlated with patient outcome. Neurotrophin receptors do not
      appear to have a prognostic role; however, Trk's may play an oncogenic role in
      olfactory neuroblastoma.

PMID- 19386346
TI  - Altered desmoplakin expression at transcriptional and protein levels provides
      prognostic information in human oropharyngeal cancer.
AB  - Desmoplakin, a desmosomal component, is a key protein involved in cell-cell
      adhesion. Down-regulation of desmosomal proteins is associated with the invasive
      and metastatic ability of tumor cells. We examined 37 cases of human primary
      oropharyngeal squamous cell carcinomas lacking overt distant metastases to gain
      further insights on the potential role of desmoplakin in oral cancer. Desmoplakin
      expression was evaluated using reverse transcriptase-polymerase chain reaction
      and immunohistochemistry on frozen unfixed sections. Western blotting was
      performed to characterize the relative expression levels for each of the 2
      desmoplakin protein isoforms, I and II. Desmoplakin expression was compared with
      histopathological grade, clinical stage, and patient outcome. Desmoplakin
      expression was prominent in highly differentiated tumors and reduced or absent in
      poorly differentiated tumors that developed distant metastases within the 3 years
      of follow-up period. Desmoplakin mRNA levels tracked with protein levels,
      suggesting that lack of desmoplakin protein expression is due to down-regulation
      of mRNA expression at the transcription level. Western blot analysis demonstrated
      that the 2 desmoplakin isoforms displayed different patterns of subcellular
      distribution in tumors, with the desmoplakin II detected only in patients in
      which desmoplakin immunoreactivity displayed an abnormal cytoplasmic
      localization. Our findings suggest that down-regulation of desmoplakin expression
      may represent a useful marker for evaluating the risk of distant metastasis
      formation in oropharyngeal squamous cell carcinomas. Interestingly, desmoplakin
      II was detected only in tumors associated with a poor clinical outcome,
      suggesting a potential specific function for this isoform in oral carcinogenesis.
      Characterizing DSP expression may improve evaluation risk of distant metastasis
      formation in oral cancer patients.

PMID- 19386347
TI  - Distinct expression of polycomb group proteins EZH2 and BMI1 in hepatocellular
      carcinoma.
AB  - Polycomb gene products play a crucial role in the development of highly malignant
      phenotypes and aggressive cancer progression in a variety of cancers; however,
      their role in hepatocellular carcinoma remains unclear. First, we analyzed the
      impact of EZH2 and BMI1 modulation on cell growth of HepG2 cells. 3-(4,5
      Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      assays revealed marked growth inhibition after EZH2 or BMI1 knockdown. In
      addition, simultaneous knockdown of these 2 genes further augmented cell growth
      inhibitory effects. Next, we conducted immunohistochemical assessment of 86
      hepatocellular carcinoma surgical specimens, evaluating the correlation between
      EZH2 and BMI1 protein expression and clinicopathologic features. High-level EZH2
      and BMI1 expression was detected in 57 (66.3%) and 52 tumor tissues (60.5%),
      respectively. Among these, 48 tumor tissues (55.8%) showed colocalization of EZH2
      and BMI1 in almost all tumor cells. The cumulative recurrence rate, but not
      survival rate, was significantly higher in patients positive for EZH2 (P = .029)
      and BMI1 (P = .039) than in their negative counterparts, as determined by Kaplan
      Meier analysis. These data indicate that EZH2 and BMI1 may cooperate in
      initiation and progression of hepatocellular carcinoma.

PMID- 19386348
TI  - Clinicopathologic analysis of patients with BK viruria and rejection-like graft
      dysfunction.
AB  - BK virus infection can be associated with interstitial inflammation, tubulitis
      without viral cytopathic effect, and negative in situ hybridization for viral
      DNA. We evaluated the consequences of increased immunosuppression in 32 viruric
      patients, with such acute cellular rejection-like changes in allograft biopsies
      (n = 50). When follow-up information was available, complete creatinine response,
      decrease in urine viral load (VL), and improvement in overall Banff grade for
      acute rejection were only seen in 13 (27%) of 49, 7 (21%) of 33, and 10 (39%) of
      26 episodes of graft dysfunction, respectively. Histologic response was not
      always accompanied by clinical response. This low rate of response to
      antirejection therapy suggests that interstitial nephritis in a subset of these
      patients was secondary to viral infection. The presence of high VL (>1.0 E+05
      copies/mL) was associated with low immune cell function values (129 +/- 99 ng of
      adenosine triphosphate per milliliter, P = .08) and with significant development
      of viremia after antirejection treatment (5/9 [56%] versus 0/24 [0%] in patients
      with low VL, P < .001).

PMID- 19386349
TI  - CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas:
      frequency, clinicopathologic features, and utility in differentiation from
      chromophobe renal cell carcinoma.
AB  - SUMMARY: Renal oncocytoma is a benign tumor occurring singly or as multiple
      synchronous lesions. The histologic features of renal oncocytoma may overlap with
      those of chromophobe renal cell carcinoma. Chromosomal translocations involving
      the CCND1 locus at 11q13 and overexpression of cyclin D1 occur in a subset of
      renal oncocytomas. We evaluated a series of 63 renal oncocytomas and 36
      chromophobe renal cell carcinomas and assessed the clinical features, cyclin D1
      overexpression by immunohistochemistry, and alterations of the CCND1 gene by
      fluorescence in situ hybridization. All 36 chromophobe renal cell carcinomas were
      negative for cyclin D1 overexpression and alterations of CCND1. Of the 63 renal
      oncocytomas, 21 (33%) showed cyclin D1 overexpression. Of 21 renal oncocytomas
      with cyclin D1 overexpression, a CCND1 rearrangement was detected in 12 (57%). A
      CCND1 rearrangement was also identified in 1 (2%) of the 42 renal oncocytomas
      without cyclin D1 overexpression. Of 42 renal oncocytomas without cyclin D1
      overexpression, 16 (38%) were from patients with multiple renal oncocytomas at
      nephrectomy. Of 21 renal oncocytomas with cyclin D1 overexpression, only 1 (5%)
      patient had multiple renal oncocytomas (P = .006). Of the 25 patients whose
      original tumor showed no cyclin D1 overexpression, 8 (32%) developed a subsequent
      renal oncocytoma. None of 15 patients whose original tumor showed cyclin D1
      overexpression had a subsequent renal oncocytoma (P = .016). The findings of this
      study suggest that renal oncocytomas lacking cyclin D1 overexpression may be
      associated with the development of multiple renal oncocytomas and that these
      patients are more likely to develop subsequent renal oncocytomas suggesting the
      need for more frequent clinical for these patients and little need for follow-up
      in patients with renal oncocytomas overexpressing cyclin D1. The data also show
      that cyclin D1 overexpression and CCND1 rearrangements by fluorescence in situ
      hybridization are absent in chromophobe renal cell carcinoma, suggesting that
      these are useful when differentiating between renal oncocytoma and chromophobe
      renal cell carcinoma.

PMID- 19386350
TI  - Anaplastic lymphoma kinase immunoreactivity correlates with ALK gene
      rearrangement and transcriptional up-regulation in non-small cell lung
      carcinomas.
AB  - Recently, the fusion gene EML4-ALK was identified in non-small cell lung
      carcinoma, which could be a potential therapeutic target. We investigated the
      prevalence of anaplastic lymphoma kinase protein expression in these tumors by
      immunohistochemistry and correlated the results with data from ALK molecular
      studies. Gene expression profiling was performed on 35 adenocarcinomas to
      identify cases with ALK gene up-regulation, which was correlated with protein
      overexpression by immunohistochemistry. Immunohistochemistry was also performed
      on an independent cohort consisting of 150 adenocarcinomas and 150 squamous cell
      carcinomas to evaluate the utility of anaplastic lymphoma kinase immunostaining
      as a screening tool. Florescence in situ hybridization for the ALK locus and
      reverse transcriptase-polymerase chain reaction for EML4-ALK were performed on
      tumors positive for anaplastic lymphoma kinase by immunohistochemistry.
      Transcriptional up-regulation of ALK was identified in 2 (6%) of 35
      adenocarcinomas by gene expression profiling. These 2 cases were positive for
      anaplastic lymphoma kinase by immunohistochemistry, whereas the remaining 33
      cases were completely negative. In the independent cohort, anaplastic lymphoma
      kinase immunostaining was positive in 1 of 150 squamous cell carcinomas and in 3
      of 150 adenocarcinomas. The 6 cases positive for anaplastic lymphoma kinase by
      immunohistochemistry showed evidence of ALK locus rearrangement by florescence in
      situ hybridization but were negative for EGFR and KRAS mutation. The presence of
      EML4-ALK fusion transcript was confirmed in 2 cases by reverse transcriptase
      polymerase chain reaction. In conclusion, anaplastic lymphoma kinase
      immunoreactivity in non-small cell lung carcinomas was associated with
      transcriptional up-regulation, ALK locus rearrangement, and the presence of EML4
      ALK fusion transcript. Anaplastic lymphoma kinase immunohistochemistry may have
      utility as a screening tool or as a surrogate marker for the molecular techniques
      to detect the EML4-ALK fusion gene in these tumors.

PMID- 19386351
TI  - High ratio of IgG4-positive plasma cell infiltration in cutaneous plasmacytosis-
      is this a cutaneous manifestation of IgG4-related disease?
AB  - Cutaneous plasmacytosis is a rare condition affecting middle-aged individuals,
      characterized by multiple red-brown papules and plaques over the trunk. It has
      been reported mainly in Japan. The condition is accompanied by polyclonal
      hypergammaglobulinemia and superficial lymphadenopathy. Lung or retroperitoneal
      involvement occurs rarely. In the present study, 3 consecutive cases of cutaneous
      plasmacytosis were observed histologically to have abundant infiltration of IgG4
      bearing plasma cells. All 3 were associated with superficial lymphadenopathy, one
      with interstitial lung involvement showing ground-glass opacity on computed
      tomography and the others with bone marrow plasmacytosis, showing histologic
      evidence of more IgG4-positive plasma cells. All 3 had polyclonal
      hypergammaglobulinemia, one had high serum concentration of IgG4, and all had
      elevated serum IL-6. The ratios of IgG4+ to IgG+ plasma cells were assessed using
      skin biopsy specimens with pemphigus (n = 7), discoid lupus erythematosus (n =
      5), and morphea (n = 2) (mean ratios, 19%, 0%, and 0%, respectively); we noted
      the proportion of IgG4-positive plasma cells in cutaneous plasmacytosis (mean,
      48%). IgG4-related sclerosing disease is a newly recognized systemic disorder
      characterized by lymphoplasmacytic infiltration and fibrosis and by a high serum
      IgG4 level and increased IgG4-positive plasma cells in the tissues. Skin
      manifestations of this disorder have not been described. Although cutaneous
      plasmacytosis could be a chronic allergic hypersensitivity reaction, our findings
      raise the possibility of a relationship in pathogenesis between cutaneous
      plasmacytosis and IgG4-related sclerosing disease.

PMID- 19386352
TI  - Antigenic profiles of individual-matched pairs of primary and melanoma
      metastases.
AB  - A unique collection of individual-matched pairs of primary and melanoma
      metastases were studied immunohistochemically with a panel of 6 monoclonal
      antibodies directed to gp-100, pigmentation-associated antigen, tyrosinase
      related protein, human leukocyte antigen DR, MAA-1, and MAA-2 (high molecular
      weight melanoma-associated antigens). The antigenic profile of immunoreactive
      pigment cells was compared with the stage of tumor progression. Our data show
      consistent antigenic profiles of primary melanomas and their metastases within
      the same patient. Expression of tyrosinase-related protein and pigmentation
      associated antigen was observed in the radial growth phase of primary melanomas
      but showed diminished or complete loss of expression in the vertical growth phase
      and in metastatic melanomas. HLA-DR was negative in the most primary lesions, but
      melanoma cells and a larger proportion of immunoreactive cells were observed at
      the metastatic site. The melanoma-associated antigens MAA-1 and MAA-2 were
      expressed throughout tumor progression. Although no clear distinction could be
      made between primary and secondary melanoma lesions for both melanoma-associated
      antigens, there was a profound variability in the topographical antigen
      distribution when compared with HLA-DR. The loss of expression of pigmentation
      associated antigen and tyrosinase-related protein in the vertical growth phase of
      the primary lesions and metastatic melanomas did not reach statistical
      significance but still may be related to tumor progression. This indicates that
      primary melanomas can be distinguished from their metastases by evaluation of the
      antigenic profile and in this respect facilitate the recognition of tumor
      progression stages.

PMID- 19386353
TI  - The definition of fibrogenic processes in fibroblastic foci of idiopathic
      pulmonary fibrosis based on morphometric quantification of extracellular
      matrices.
AB  - There is limited information regarding the process of tissue remodeling in
      fibroblastic foci associated with idiopathic pulmonary fibrosis. The aim of this
      study was to identify the different pathologic stages of tissue remodeling in
      fibroblastic foci based on the histopathologic differences in the
      glycosaminoglycan distribution and collagen deposition. In addition, we also
      aimed at clarifying the stage-specific characteristics by taking into
      consideration the expression pattern of matrix metalloproteinase and
      angiogenesis. Lung biopsies of 16 patients with idiopathic pulmonary fibrosis
      were used. The presence of glycosaminoglycans was detected by Alcian blue
      staining, and type I collagen was detected by immunohistochemical analysis with a
      primary antibody specific to the cross-linked carboxyterminal telopeptide of type
      I collagen. The fibroblastic foci characterized by the expression intensity of
      Alcian blue and telopeptide of type I collagen were divided into 3 groups,
      namely, Alcian blue(+)telopeptide of type I collagen(weak), Alcian
      blue(+)telopeptide of type I collagen(+), and Alcian blue(weak)telopeptide of
      type I collagen(+); consequently, 3 new stages were defined--stages I, II, and
      III, respectively. A significant inverse correlation was observed between the
      area densities of Alcian blue(+) and telopeptide of type I collagen(+) in
      fibroblastic foci. Stage I was characterized by the expression of matrix
      metalloproteinase-2 and tissue inhibitor of matrix metalloprotease-2 in
      fibroblasts and the overlying epithelium of fibroblastic foci, and also the
      absence of capillary angiogenesis. In contrast, the expression of these proteins
      was attenuated in stage III, except for that of matrix metalloproteinase-2 in
      fibroblasts. In stages II and III, capillary angiogenesis was observed.
      Lymphangiogenesis was undetected in all the 3 stages. Thus, pathologic staging
      helps understand the roles of the factors involved in tissue remodeling in
      idiopathic pulmonary fibrosis.

PMID- 19386354
TI  - Neuropathology in 2 cases of fatal enterovirus type 71 infection from a recent
      epidemic in the People's Republic of China: a histopathologic,
      immunohistochemical, and reverse transcription polymerase chain reaction study.
AB  - Between late March and June of 2008, an outbreak of hand, foot, and mouth disease
      caused by enterovirus 71 occurred in China. In this outbreak, more than 176,000
      cases occurred, and at least 40 people died. However, there has been no
      description of the neuropathologic features of fatal enterovirus 71 infection
      cases during this outbreak. We report postmortem studies in 2 fatal cases of
      enterovirus 71 infection with examination of the central nervous system using
      histopathology, immunohistochemistry, and reverse transcription polymerase chain
      reaction. Characteristic features of acute encephalitis were found predominantly
      in the brain stem and spinal cord. Abundant numbers of inflammatory cells with
      unusual irregularly rod-shaped and lobulated nuclei, which mimicked neutrophil
      morphology, were found both in abscess-like clusters associated with necrosis, as
      well as in inflammatory infiltrates. Immunohistochemistry showed that most of
      these cells were CD68 positive and CD15 negative. Viral antigens were found in
      the cytoplasm of neurons, neuronal processes, and inflammatory cells, most often
      associated with glial nodules. The presence of enterovirus 71 was confirmed by
      reverse transcription polymerase chain reaction and sequencing. Results indicate
      that immunohistochemistry with CD68 and CD15 may offer some help in the
      differential diagnosis of brain stem encephalitis caused by enterovirus 71.
      Postmortem reverse transcription polymerase chain reaction from brain stem
      tissues, which have already undergone fixation and histologic processing, can be
      an important diagnostic tool, which may be of particular value in patients who
      may have been misdiagnosed clinically.

PMID- 19386355
TI  - A short cytochemical note on the nucleolar and cytoplasmic RNA concentration in
      differentiating cells represented by human erythroblasts.
AB  - The present study was undertaken to provide more information on the nucleolar and
      cytoplasmic RNA concentration in differentiating cells of the erythroid lineage.
      These cells represent a convenient model to study cell differentiation since all
      stages are morphologically well characterised. The bone marrow of patients
      suffering from the chronic phase of chronic myeloid leukaemia without a large
      increase in the granulocyte to erythroid ratio provided erythroblasts for
      computer-assisted image density measurements of RNA in nucleoli and cytoplasm at
      the single cell level. The measurements indicated a significant decrease of the
      nucleolar and cytoplasmic RNA concentration only in advanced stages of
      erythroblast differentiation (polychromatic and orthochromatic erythroblasts).
      The ratio of the nucleolar to cytoplasmic RNA concentration was otherwise very
      stable and did not change during differentiation, being similar in the early and
      advanced stages of erythroblastic development. In contrast, the nucleolar size
      significantly decreased even during the early stages of erythroid development
      (basophilic erythroblasts). This marked decrease in the nucleolar diameter in
      differentiating erythroblasts and the less marked decrease in the nucleolar RNA
      concentration suggest that the amount of RNA in the nucleolus is closely
      associated with nucleolar size rather than on its concentration within the
      nucleolar body.

PMID- 19386356
TI  - Resuscitation at birth and long-term follow-up.

PMID- 19386358
TI  - CDKN1C mutations in HELLP/preeclamptic mothers of Beckwith-Wiedemann Syndrome
      (BWS) patients.
AB  - Preeclampsia is the development of new-onset hypertension with proteinuria after
      20 weeks of gestation. HELLP syndrome (haemolysis, elevated liver enzymes, and
      low platelet count) is a severe form of preeclampsia with high rates of neonatal
      and maternal morbidity. In recent years, loss of function of cdkn1c (a tight
      binding inhibitor of G1 cyclin/cyclin-dependent kinase complexes and a negative
      regulator of cell proliferation) has been observed in several mouse models of
      preeclampsia. In this paper, we report on three women with HELLP/preeclampsia who
      had children with Beckwith Wiedemann syndrome, a complex genetic disorder
      characterised, among other findings, by overgrowth, omphalocele and macroglossia.
      All three children displayed mutations in CDKN1C predicted to generate truncated
      proteins. Two of the mutations were maternally inherited while the third was de
      novo. This finding suggests a fetal contribution to the maternal disease. To the
      best of our knowledge this is the first report of CDKN1C mutations in children
      born to women with preeclampsia/HELLP syndrome, thus suggesting the involvement
      of an imprinted gene in the pathophysiology of preeclampsia.

PMID- 19386357
TI  - Resuscitation at birth and cognition at 8 years of age: a cohort study.
AB  - BACKGROUND: Mild cerebral injury might cause subtle defects in cognitive function
      that are only detectable as the child grows older. Our aim was to determine
      whether infants receiving resuscitation after birth, but with no symptoms of
      encephalopathy, have reduced intelligence quotient (IQ) scores in childhood.
      METHODS: Three groups of infants were selected from the Avon Longitudinal Study
      of Parents and Children: infants who were resuscitated at birth but were
      asymptomatic for encephalopathy and had no further neonatal care (n=815), those
      who were resuscitated and had neonatal care for symptoms of encephalopathy
      (n=58), and the reference group who were not resuscitated, were asymptomatic for
      encephalopathy, and had no further neonatal care (n=10 609). Cognitive function
      was assessed at a mean age of 8.6 years (SD 0.33); a low IQ score was defined as
      less than 80. IQ scores were obtained for 5953 children with a shortened version
      of the Weschler intelligence scale for children (WISC-III), the remaining 5529
      were non-responders. All children did not complete all parts of the test, and
      therefore multiplied IQ values comparable to the full-scale test were only
      available for 5887 children. Results were adjusted for clinical and social
      covariates. Chained equations were used to impute missing values of covariates.
      FINDINGS: In the main analysis at 8 years of age (n=5887), increased risk of a
      low IQ score was recorded in both resuscitated infants asymptomatic for
      encephalopathy (odds ratio 1.65 [95% CI 1.13-2.43]) and those with symptoms of
      encephalopathy (6.22 [1.57-24.65]). However, the population of asymptomatic
      infants was larger than that of infants with encephalopathy, and therefore the
      population attributable risk fraction for an IQ score that might be attributable
      to the need for resuscitation at birth was 3.4% (95% CI 0.5-6.3) for asymptomatic
      infants and 1.2% (0.2-2.2) for those who developed encephalopathy.
      INTERPRETATION: Infants who were resuscitated had increased risk of a low IQ
      score, even if they remained healthy during the neonatal period. Resuscitated
      infants asymptomatic for encephalopathy might result in a larger proportion of
      adults with low IQs than do those who develop neurological symptoms consistent
      with encephalopathy. FUNDING: Wellcome Trust.

PMID- 19386359
TI  - Increase of intracellular Ca2+ by adenine and uracil nucleotides in human
      midbrain-derived neuronal progenitor cells.
AB  - Nucleotides play an important role in brain development and may exert their
      action via ligand-gated cationic channels or G protein-coupled receptors. Patch
      clamp measurements indicated that in contrast to AMPA, ATP did not induce
      membrane currents in human midbrain derived neuronal progenitor cells (hmNPCs).
      Various nucleotide agonists concentration-dependently increased [Ca(2+)](i) as
      measured by the Fura-2 method, with the rank order of potency ATP>ADP>UTP>UDP. A
      Ca(2+)-free external medium moderately decreased, whereas a depletion of the
      intracellular Ca(2+) storage sites by cyclopiazonic acid markedly depressed the
      [Ca(2+)](i) transients induced by either ATP or UTP. Further, the P2Y(1) receptor
      antagonistic PPADS and MRS 2179, as well as the nucleotide catalyzing enzyme
      apyrase, allmost abolished the effects of these two nucleotides. However, the
      P2Y(1,2,12) antagonistic suramin only slightly blocked the action of ATP, but
      strongly inhibited that of UTP. In agreement with this finding, UTP evoked the
      release of ATP from hmNPCs in a suramin-, but not PPADS-sensitive manner.
      Immunocytochemistry indicated the co-localization of P2Y(1,2,4)
      immunoreactivities (IR) with nestin-IR at these cells. In conclusion, UTP may
      induce the release of ATP from hmNPCs via P2Y(2) receptor-activation and thereby
      causes [Ca(2+)](i) transients by stimulating a P2Y(1)-like receptor.

PMID- 19386360
TI  - Squid nerve Na+/Ca2+ exchanger expressed in Saccharomyces cerevisiae: up
      regulation by a phosphorylated cytosolic protein (ReP1-NCXSQ) is identical to
      that of native exchanger in situ.
AB  - This work shows, for the first time, a properly metabolically regulated squid
      nerve Na(+)/Ca(2+) exchanger (NCXSQ1) heterologous expressed in Saccharomyces
      cerevisiae. The exchanger was fused to the enhanced green fluorescence protein
      (eGFP) on its C-terminus and had two tags, a Strep-tag II and 6 histidines, added
      to the N-terminal region (ST-6HB-NCXSQ1-eGFP). The eGFP fluorescence signal co
      localized with that of the plasma membrane marker FM1-43 in whole cells that
      displayed an uptake of Ca(2+) with the expected characteristics of the reverse
      Na(+)/Ca(2+) exchange mode. Similar to squid nerve membrane vesicles, inside-out
      yeast plasma membrane vesicles (ISOV) showed a Ca(2+)(i) regulation of the
      forward mode that was modulated by previously phosphorylated regulatory cytosolic
      protein (ReP1-NCXSQ). On the other hand, a close association between NCXSQ1 and
      ReP1-NCXSQ, estimated by co-immunoprecipitation, was independent of ReP1-NCXSQ
      phosphorylation. An additional crucial observation was that in proteoliposomes
      containing only the ST-6HB-NCXSQ1-eGFP protein, Na(+)/Ca(2+) exchange was
      stimulated by phosphorylated ReP1-NCXSQ; i.e., this up-regulation needs no other
      requirement besides the lipid membrane and the exchanger protein. Finally, this
      work provides a potential approach to obtain enough purified NCXSQ1 for
      structural and biochemical studies which have been delayed due to the lack of
      sufficient material.

PMID- 19386361
TI  - Extended rituximab schedules may result in increased efficacy in pulmonary malt
      lymphoma.

PMID- 19386362
TI  - Phytoremediation of heavy-metal-polluted soils: screening for new accumulator
      plants in Angouran mine (Iran) and evaluation of removal ability.
AB  - Heavy metal pollution is a worldwide problem. Phytoremediation is an effective
      and low-cost interesting technology. This study was conducted in a dried waste
      pool of a lead and zinc mine in Angouran (Iran) to find accumulator plant(s).
      Concentrations of heavy metals were determined both in the soil and the plants
      that were grown in the mine and out of mine. The concentration of total Cu, Fe,
      Zn, Pb and Ni in the mine area were higher than the control soil. The results
      showed that five dominant vegetations namely Amaranthus retroflexus, Polygonum
      aviculare, Gundelia tournefortii, Noea mucronata and Scariola orientalis
      accumulated heavy metals. Based on the results, it was concluded that N.
      mucronata is the best accumulator for Pb, Zn, Cu, Cd and Ni, but the best Fe
      accumulator is A. retroflexus. Phytoremediation ability of N. mucronata was
      evaluated in experimental pots. The study showed that the amounts of heavy metals
      were decreased in polluted soils during experiments. The accumulation of metals
      in the root, leave and shoot portions of N. mucronata varied significantly but
      all the concentrations were more than natural soils. The results indicated that
      N. mucronata is an effective accumulator plant for phytoremediation of heavy
      metals-polluted soils.

PMID- 19386363
TI  - Role of a distal enhancer in the transcriptional responsiveness of the human
      CD200 gene to interferon-gamma and tumor necrosis factor-alpha.
AB  - CD200 plays an important role in prevention of graft rejection, autoimmune
      diseases and spontaneous abortion by delivering an immunoregulatory signal
      through interaction with its receptor. It also plays a role in regulating tumor
      immunity. We previously documented evidence for C/EBP beta as being important in
      the regulation of constitutive expression of CD200. However, the molecular
      mechanism(s) controlling inducible expression of CD200 are yet to be explored.
      Here we address the regulated expression of human CD200 by T cells in response to
      Con A, IFN-gamma or/and TNF-alpha. A prominent DNase I hypersensitivity site
      (DHS) was localized approximately 5.4 kb upstream of the major transcriptional
      start site. Four cis-elements were identified within this genomic region: one
      nuclear factor-kappaB (NF-kappaB) site, one IFN-gamma activation site (GAS)
      element and two IFN-stimulated response element (ISRE) for binding of interferon
      regulatory factors (IRFs), respectively. Mutation of the NF-kappaB site, GAS or
      one but not the other of ISREs dramatically reduced the luciferase activity.
      These findings were further confirmed by chromatin immunoprecipitation (ChIP)
      assays using antibodies against NF-kappaB p65, STAT1alpha, and IRF-1. All the
      above findings suggest that IFN-gamma and TNF-alpha induce CD200 expression
      through a 5' upstream enhancer and that NF-kappaB, STAT1 and IRF-1 play pivotal
      roles in this process.

PMID- 19386364
TI  - Copper.Lys-Gly-His-Lys mediated cleavage of tRNA(Phe): studies of reaction
      mechanism and cleavage specificity.
AB  - The reactivity of [Cu2+.Lys-Gly-His-Lys-NH2]2+ and [Cu2+.Lys-Gly-His-Lys]+ toward
      tRNA(Phe) has been evaluated. The amidated and carboxylate forms of the copper
      peptides display complex binding behavior with strong and weak sites evident
      (K(D1)(app) approximately 71 microM, K(D2)(app) approximately 211 microM for the
      amide form; and K(D1)(app) approximately 34 microM, K(D2)(app) approximately 240
      microM for the carboxylate form), while Cu2+(aq) yielded K(D1)(app) approximately
      81 microM and K(D2)(app) approximately 136 microM. The time-dependence of the
      reaction of [Cu2+.Lys-Gly-His-Lys]+ and [Cu2+.Lys-Gly-His-Lys-NH2]2+ with
      tRNA(Phe) yielded k(obs) approximately 0.075 h(-1) for both complexes. HPLC
      analysis of the reaction products demonstrated guanine as the sole base product.
      Mass spectrometric data shows a limited number of cleavage fragments with product
      peak masses consistent with chemistry occurring at a discrete site defined by the
      structurally contiguous D and TPsiC loops, and in a domain where high affinity
      magnesium centers have previously been observed to promote hydrolysis of the
      tRNA(Phe) backbone. This cleavage pattern is more selective than that previously
      observed by Long and coworkers for nickel complexes of a series of C-terminally
      amidated peptides (Gly-Gly-His, Lys-Gly-His, and Arg-Gly-His), and may reflect
      variations in structural recognition and a distinct reaction path by the nickel
      derivatives. The data emphasizes the optimal positioning of the metal-associated
      reactive oxygen species, relative to scissile bonds, as a major criterion for
      development of efficient catalytic nucleases or therapeutics.

PMID- 19386365
TI  - Synthesis, characterization of strontium-bile acid salts and their bioactivity
      vs. the anti-osteoporosis drug strontium ranelate.
AB  - The strontium salts Sr(cholate)2, (Compound 1), Sr(dehydrocholate)2, (Compound 2)
      and Sr3(3-dehydrocholanoyliden-L-tartrate)2, (Compound 3) have been prepared and
      characterized. The potential anti-osteoporotic activity of these compounds was
      tested on human primary osteoblasts (hOBs) and human primary osteoclasts (hOCs)
      in comparison with the bioactivity of strontium ranelate, previously registered
      as drug in the treatment of post-menopausal osteoporosis. Our results led to the
      hypothesis that the tested compounds, particularly Compound 2, may have
      requirements for modulating skeletal tissue regeneration or at least down
      regulating the loss of bone mass. In fact, all tested compounds have been shown
      to induce maturation in human primary osteoblasts (hOBs) and apoptosis of human
      primary osteoclasts (hOCs) at the same time.

PMID- 19386366
TI  - Prognostic factors for fatal adult influenza pneumonia.
AB  - OBJECTIVES: To elucidate the prognostic factors for fatal adult influenza
      pneumonia. METHODS: Complicated influenza pneumonia is a notifiable disease in
      Taiwan. In this retrospective nationwide cohort, medical records were reviewed in
      38 qualifying cases from 2001 to 2007. In-hospital mortality was the primary
      endpoint of this study. RESULTS: The median patient age was 52 years, with the in
      hospital mortality rate of 44.7%. Influenza A virus was found in 25 patients and
      influenza B was in 13 patients. Fifty percent of patients had no comorbidities.
      More than half of the patients developed sepsis, septic shock, respiratory
      failure or acute respiratory distress syndrome. The median duration from symptom
      onset to hospital visit was 3 days, and from hospital visit to death was 4 days.
      A univariate analysis demonstrated poor prognosis in patients with shock,
      respiratory rate > or =25/min, arterial pH<7.35, creatinine> or =2mg/dL and
      Pneumonia Severity Index IV or V. A multivariate analysis showed an association
      with mortality in patients with APACHE II score > or =20 (hazard ratio 5.941,
      p=0.024) or PaO(2)/FiO(2) ratio <150 (hazard ratio 4.194, p=0.017). CONCLUSIONS:
      Clinical knowledge of identified prognostic factors for mortality may aid
      management of adult influenza pneumonia.

PMID- 19386367
TI  - Aspirin and infective endocarditis: an ancient medicine used to fight an ancient
      disease-but does it work?

PMID- 19386368
TI  - Novelty seeking: difference between suicidal and non-suicidal Hungarian
      adolescent outpatients suffering from depression.
AB  - AIMS: The aim of the study was to explore possible differences in temperament and
      character dimensions between two focused clinical adolescent groups, namely
      suicidal (1) and non-suicidal (2) depressive adolescent outpatients. SAMPLE: From
      a multisite Western-Hungarian sample of consecutively referred 14-18 year old new
      psychiatric outpatients, two groups of adolescent outpatients were compared:
      Group I, n=39 (9 boys, 30 girls) "Suicidal-depressives" and Group II, n=51 (12
      boys, 39 girls) "Non-suicidal depressives". Other diagnoses as major depression
      and/or dysthymia and suicidal behaviour were excluded including bipolar disorder,
      and the groups were matched by age, sex and family status. Assessment methods
      used were the Hungarian standard versions of the Mini International
      Neuropsychiatric Interview (M.I.N.I Plus), and the Junior Temperament (Cloninger)
      Character Inventory (JTCI). RESULTS: The only difference between the groups was
      that suicidal-depressive adolescents exhibited significantly higher novelty
      seeking compared to "pure" depressive clinical peers. CONCLUSIONS: More research
      and the use of closer clinical personality typologies are warranted to explore
      the fine differences between these two clinical groups of depressive adolescent
      patients that are similar to each other in many aspects: suicidal and non
      suicidal youngsters.

PMID- 19386369
TI  - The expression pattern of TIR8 is conserved among vertebrates.
AB  - IL-1R/TLRs play an important role in the inflammatory responses. Their signaling
      pathway is tightly regulated to keep inflammation under control. The regulation
      involves both extracellular and intracellular mechanisms. TIR8, also known as
      SIGIRR (Single Immunoglobulin IL-1R-Related molecule), is an orphan receptor
      belonging to the IL-1R/TLRs super-family. Recent studies suggest its role in
      modulating the inflammatory response in the gastrointestinal tract in mice,
      acting as an IL-1 receptor family antagonist. We identified the sequence and
      analyzed the expression of TIR8 in a wide panel of organs and tissues in
      different animals. There was high homology of the cDNA sequence among human,
      mouse and the domestic species (74-85%). The pattern of expression of this
      receptor was similar in all the species examined (high levels in kidney and
      gastrointestinal tract) and similar to the human. These results demonstrate that
      TIR8 is conserved, in evolutionary terms, both with regard to sequence and
      pattern of expression, a finding consistent with a key function of this molecule
      in modulating inflammation in the gastrointestinal tract.

PMID- 19386370
TI  - 17beta-Estradiol inhibits chondrogenesis in the skull development of zebrafish
      embryos.
AB  - 17beta-Estradiol (E2) plays important roles in the development and
      differentiation of the gonad and central nervous systems, but little is known
      regarding the effects of exogenous E2 on chondrogenesis in skeletal development.
      In the present study, we found that treatment with E2 1-5 days post-fertilization
      (dpf) at concentrations above 1.5x10(-5)M increased the mortality rate in
      zebrafish embryos. Morphological analysis showed that treatment with E2 1-5dpf
      caused abnormal cartilage formation in a dose-dependent manner at concentrations
      above 5x10(-6)M. E2 1-5dpf at 1.5x10(-5)M caused defects of the ethmoid plate,
      parallel cleft of the trabecular cartilage, and hypoplasia of Meckel's cartilage
      and the ceratohyal cartilage. The sensitivity of embryos to E2 depended on the
      developmental stage. In early chondrogenesis (1-2dpf), the embryos were highly
      sensitive to E2, leading to hypoplasia of the cartilage. In situ hybridization
      studies showed that expression levels of patched1 (ptc1) and patched2 (ptc2)
      receptor mRNAs were markedly decreased by exposure to 2x10(-5)M E2 1-2dpf.
      However, the expression levels of sonic hedgehog (shh) and tiggywinkle hedgehog
      (twhh) mRNAs were constant in the E2-treated embryos. In addition, the estrogen
      receptor antagonist ICI 182,780 did not completely abolish the effects of E2,
      suggesting that E2 may not inhibit chondrogenesis through its nuclear estrogen
      receptor. These results suggest that exposure to exogenous E2 possibly inhibits
      chondrogenesis via inhibition of the hedgehog (Hh) signal transduction system.

PMID- 19386371
TI  - Evidence of impaired coronary flow reserve and elevated microvascular resistances
      in a case of recurrent left apical ballooning.
AB  - A 56-year old man was admitted for precordial pain associated with dyspnea and
      evidence of myocardial ischemia on ECG and cardiac ultrasound. His previous
      history included an episode of left apical ballooning five years before. At
      angiography, no evidence of significant epicardial coronary artery disease was
      manifest. Interestingly, both coronary flow reserve and the index of
      microvascular resistances were abnormal, showing evidence of impaired
      microvascular function. This is the first report providing direct evidence of
      microvascular dysfunction in a patient with (recurrent) apical ballooning.

PMID- 19386372
TI  - Predictive ability of the SCORE Belgium risk chart for cardiovascular mortality.
AB  - BACKGROUND: The identification of persons at high cardiovascular risk is of
      primary importance in the context of cardiovascular prevention. Accuracy and
      precision of risk assessment are essential properties. We developed a calibrated
      SCORE risk chart (Systematic COronary Risk Evaluation) for calculating the
      absolute 10-year probability of developing a fatal cardiovascular event, adapted
      to national mortality statistics and risk factor distributions in Belgium and
      critically evaluated its predictive accuracy. METHODS: Our SCORE Belgium risk
      chart was validated using data from 6212 non-diabetic men and women free of CHD
      participating in a prospective cohort study carried out in the eighties (Belgian
      Interuniversity Research on Nutrition and Health). Agreement between numbers of
      predicted and observed CVD deaths across the entire spread of risk was studied
      using chi-square and Hosmer-Lemeshow statistics. Discriminatory power of risk
      estimates was evaluated according to Harrell's c-statistic. RESULTS: During the
      period of 10 years, 274 CVD deaths were observed while the recalibrated risk
      chart predicted 263 events. The SCORE Belgium risk chart showed very good
      accuracy over the complete range of predicted risk (Hosmer-Lemeshow: P=0.14). ROC
      analysis revealed excellent discriminatory power in labelling future cases of
      fatal cardiovascular disease with a c-statistic of 0.86. The 5% threshold for the
      probability of 10-year cardiovascular death yielded an optimal balance of
      sensitivity and specificity. CONCLUSIONS: The SCORE Belgium risk chart proves to
      be well suited as an accurate and precise estimation tool for the assessment of
      cardiovascular risk in Belgium.

PMID- 19386373
TI  - Hybrid palliation in complex congenital heart malformation with duct-dependent
      isolated pulmonary artery.
AB  - A 2 month-old infant with severe congestive heart failure due to unrestrictive
      ventricular septal defect and absence of the left pulmonary artery was submitted
      to a hybrid transcatheter-surgical palliation consisting in percutaneous re
      canalization of the occluded arterial duct-left pulmonary artery complex and
      surgical banding of the right pulmonary artery. The post-operative course was
      uneventful and the baby was discharged in a few days under mild anti-congestive
      therapy. This hybrid approach was highly effective in stabilizing this critical
      infant in view of a later and safer surgical repair.

PMID- 19386374
TI  - Molecular and cellular mechanisms of aortic stenosis.
AB  - Calcific aortic stenosis is the most common cause of aortic valve replacement in
      developed countries, and this condition increases in prevalence with advancing
      age. The fibrotic thickening and calcification are common eventual endpoint in
      both non-rheumatic calcific and rheumatic aortic stenoses. New observations in
      human aortic valves support the hypothesis that degenerative valvular aortic
      stenosis is the result of active bone formation in the aortic valve, which may be
      mediated through a process of osteoblast-like differentiation in these tissues.
      Additionally histopathologic evidence suggests that early lesions in aortic
      valves are not just a disease process secondary to aging, but an active cellular
      process that follows the classical "response to injury hypothesis" similar to the
      situation in atherosclerosis. Although there are similarities with the risk
      factor and as well as with the process of atherogenesis, not all the patients
      with coronary artery disease or atherosclerosis have calcific aortic stenosis.
      This review mainly focuses on the potential vascular and molecular mechanisms
      involved in the pathogenesis of aortic valve stenosis. Namely extracellular
      matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like
      differentiation resulting in bone formation have been shown to play a role in the
      pathogenesis of calcific aortic stenosis. Several mediators related to underlying
      mechanisms, including growth factors especially transforming growth factor-beta1
      and vascular endothelial growth factors, angiogenesis, cathepsin enzymes,
      adhesion molecules, bone regulatory proteins and matrix metalloproteinases have
      been demonstrated, however the target to be attacked is not defined yet.

PMID- 19386375
TI  - Isolation of adhesive strains and evaluation of the colonization and immune
      response by Lactobacillus plantarum L2 in the rat gastrointestinal tract.
AB  - Five Lactobacillus strains were tested for their ability to adhere to Caco-2 and
      IEC-6 cell lines as in vitro models and to induce of the secretion of pro- and
      anti-inflammatory cytokines by human peripheral blood mononuclear cells (PBMCs).
      Among the tested strains, Lactobacillus plantarum L2 was the most adhesive
      strain, approximately 595+/-125 or 704+/-273 of the added bacteria adhered to
      Caco-2 or IEC-6 cell cultures, respectively. Furthermore, L. plantarum L2 was
      also found to induce a considerable level of IL-10 from PBMCs, but low levels of
      all three pro-inflammatory cytokines TNF-alpha, IFN-gamma and IL-12. From these
      results, one promising strain, L. plantarum L2, was selected for in vivo studies.
      For 28 days F344 rats were fed a daily dose of 2 x 10(9)L. plantarum L2; for the
      next 14 days the rats were not fed any Lactobacillus. Intestinal mucosal samples
      and feces were taken at days 0, 28 and 42 to determine the colonizing ability of
      the lactobacilli. Recovered Lactobacillus isolates were initially identified by
      API 50CHL and strain-specific PCR. Intestinal specimen was analyzed using
      fluorescence in situ hybridization with a strain-specific molecular probe, and
      immune cell populations were determined by immunostaining for evidence of immune
      responses at the colonized sites. After intake of L. plantarum L2 for 28 days, a
      significant increase in live L. plantarum was found in the rats' feces, small
      intestine and colon. The bacterial levels remained high even after the L.
      plantarum L2 administration had been stopped for two weeks. Strain-specific PCR
      and FISH provided clear and direct evidence of colonization of the rat
      gastrointestinal tract by L. plantarum L2. Additionally, a significant increase
      in CD19-positive cells in the ileum was observed after intake of L. plantarum L2.
      In conclusion, dietary supplementation with L. plantarum L2 induced significant
      colonization of the gastrointestinal tract of rats, and this was associated with
      significant alteration of the immune response in the gastrointestinal mucosa.

PMID- 19386376
TI  - Prevalence and virulence properties of non-O1 non-O139 Vibrio cholerae strains
      from seafood and clinical samples collected in Italy.
AB  - Seafood and clinical samples collected in Italy during 2006 were analyzed to
      evaluate prevalence, serological and virulence properties of non-O1 non-O139
      Vibrio cholerae (NCV) isolates. Biochemical and serological characterization of
      the strains was performed by standardized procedures while virulence properties
      of NCVs were assayed by molecular, in vivo and in vitro toxicological methods. Of
      the 300 seafood samples examined, including mussel, cod, mackerel, anchovy, clam,
      prawn and cuttlefish, 5.6% were positive for NCVs: 4.7% and 8.5% from local and
      imported seafood, respectively. The prevalence of NCVs was highest in prawn
      (16.6%) and mussel (7.7%). Of 58 hospitalized patients that presented acute
      diarrhea, 3.4% eliminated NCVs in stools 24-48 h after consumption of seafood.
      All NCVs had ToxR and hlyAET genes but lacked ctxA, zot, and tcpA genes. One
      isolate from prawn had stn/sto gene. All strains were hemolytic, cytotoxic, and
      able to induce intestinal and extraintestinal effects on the suckling mouse
      model. Our results confirm that non-toxigenic NCVs that express the gene encoding
      El Tor-like hemolysin can be isolated from patients suffering a cholera-like
      syndrome after consumption of seafood. This evidence along with the virulence and
      enteropathogenicity of all the ctxA(-) tcpA(-) zot(-) stn/sto(-) hlyAET(+) NCV
      isolates in the experimental model, suggest that El Tor-like hemolysin may play
      an important role in human pathogenesis. Moreover, the isolates from seafood
      showed molecular, biological and enzymatic patterns similar to those isolated
      from clinical samples, underlining that environmental NCVs are potentially able
      to induce human infections and confirming the important role of seafood as a
      vehicle of V. cholerae diseases.

PMID- 19386377
TI  - Study of the phenotypic and genotypic biodiversity of potentially ochratoxigenic
      black aspergilli isolated from grapes.
AB  - Ochratoxin A (OTA) is a mycotoxin with nephrotoxic, carcinogenic, teratogenic and
      immunotoxic effects, naturally found in agricultural products including grapes
      and wine. Black Aspergillus species (Section Nigri) are mainly responsible for
      OTA accumulation in wine grapes and in particular Aspergillus carbonarius and
      Aspergillus niger aggregate. The biodiversity of potentially ochratoxigenic
      strains of black aspergilli from different French vineyards in the southern
      Mediterranean region of Languedoc-Roussillon was studied. One hundred and eighty
      nine black strains were isolated from grapes and studied according to harvest
      year, production zone, grape variety and pre-harvest treatment of grapevines. The
      strains were identified and classified in two groups according to macroscopic and
      microscopic characters; these were called the A. carbonarius representative group
      and the A. niger aggregate representative group. Members of each group were
      classified in subgroups based on macroscopic morphological colony characters.
      Strain biodiversity was studied according to phenotypic and genotypic
      characterization and to the OTA production of selected strains on PDA medium.
      After identification was confirmed by specific PCR using primer pair ITS1/CAR and
      ITS1/NIG, 24 potential ochratoxigenic strains belonging to A. carbonarius and A.
      niger aggregate were discriminated by RAPD-PCR using 8 different OPC primers. The
      use of specific primers supported the identification based on phenotypic and
      morphological characters. RAPD-PCR patterns demonstrated a considerable diversity
      among the strains. Clustering among A. niger aggregate strains was associated
      with production zone and harvest year, but not grape variety or pre-harvest
      treatment. Clustering among A. carbonarius strains was not associated with any of
      the above parameters. OTA production of strains on culture medium seemed to
      correlate better with morphological characters than with genotypic profiles. No
      clear relation could be established between phenotypic and genotypic characters
      of the studied black aspergilli.

PMID- 19386378
TI  - Medical diagnostic process optimization through the semantic integration of data
      resources.
AB  - In this paper we study the optimization of medical diagnostic process from the
      data access point of view. According to many studies which showed that optimized
      diagnostic process can considerably improve efficiency in health care industry,
      we present a new approach to data integration within a diagnostic process. It is
      our belief that a unified access to data resources throughout the whole
      diagnostic process considerably improves the efficiency of the process itself.
      When combining the optimized data access with an existing algorithmic
      optimization method an optimized process can be achieved that takes into account
      the quality of a diagnosis, the individual needs of each patient, the associated
      costs, and the utilization of personnel/equipment. To enable an efficient
      management of data, we developed a semantic web based system for the integration
      of data resources within a medical diagnostic process. Then we combined the
      unified data access with our existing diagnostic process optimization framework
      that uses machine learning techniques and evolutionary algorithms. The new
      defined diagnostic process framework is finally used in a case-study for
      optimizing the diagnosing of the mitral valve prolapse syndrome in a regional
      hospital department.

PMID- 19386379
TI  - Analytical modelling of fringe and core biodegradation in groundwater plumes.
AB  - Biodegradation can be divided into two categories depending on the location at
      which it occurs within the plume: degradation at the plume fringes, and
      degradation in the interior (core). Available analytical solutions are limited to
      the consideration of either fringe or core degradation, which in turn limits the
      applicability of these solutions. Here, a new analytical approach to modelling
      plumes with both fringe and core degradation is presented. The approach relies on
      the use of readily available analytical solutions for solute transport. Using a
      well-known solution for three-dimensional solute transport from a planar source,
      an approximate solution is derived for the maximum plume length at steady-state
      conditions. This is verified through the use of a numerical solution. The
      solution suggests that the parameters controlling the plume length are: (i) the
      size of the contaminant source, (ii) electron acceptor to electron donor ratio,
      (iii) transverse dispersivities and (iv) the ratio between degradation rate
      constant and velocity (lambda/v). The latter term provides a simple check on the
      relative weights of transport to core degradation and can be used to estimate the
      importance of core degradation in the overall plume attenuation. The well
      documented Bemidji field site has both fringe and core degradation. The new
      combined degradation model estimates the length of the plume with 10 m of the
      observed length; core only and fringe only solutions overestimate the length by
      more than a factor of 2.

PMID- 19386380
TI  - Monodehydroascorbate reductase 2 and dehydroascorbate reductase 5 are crucial for
      a mutualistic interaction between Piriformospora indica and Arabidopsis.
AB  - Ascorbate is a major antioxidant and radical scavenger in plants.
      Monodehydroascorbate reductase (MDAR) and dehydroascorbate reductase (DHAR) are
      two enzymes of the ascorbate-glutathione cycle that maintain ascorbate in its
      reduced state. MDAR2 (At3g09940) and DHAR5 (At1g19570) expression was upregulated
      in the roots and shoots of Arabidopsis seedlings co-cultivated with the root
      colonizing endophytic fungus Piriformospora indica, or that were exposed to a
      cell wall extract or a culture filtrate from the fungus. Growth and seed
      production were not promoted by Piriformospora indica in mdar2 (SALK_0776335C)
      and dhar5 (SALK_029966C) T-DNA insertion lines, while colonized wild-type plants
      were larger and produced more seeds compared to the uncolonized controls. After 3
      weeks of drought stress, growth and seed production were reduced in
      Piriformospora indica-colonized plants compared to the uncolonized control, and
      the roots of the drought-stressed insertion lines were colonized more heavily by
      the fungus than were wild-type plants. Upregulation of the message for the
      antimicrobial PDF1.2 protein in drought-stressed insertion lines indicated that
      MDAR2 and DHAR5 are crucial for producing sufficient ascorbate to maintain the
      interaction between Piriformospora indica and Arabidopsis in a mutualistic state.

PMID- 19386381
TI  - Clostridium difficile ribotypes 027 and 106: clinical outcomes and risk factors.
AB  - The present study investigates risk factors for onset of Clostridium difficile
      associated diarrhoea, specific ribotype and environmental spore contamination in
      a District General Hospital in South East England. C. difficile isolates were
      ribotyped from 97 diarrhoeal cases, following detection of C. difficile toxin
      from faecal specimens by enzyme immunoassay (Health Protection Agency,
      Southampton). The isolates were tested for various antimicrobial susceptibilities
      by E-test. Cases were assessed for prior antibiotic use and followed up for
      clinical outcomes. Controls were matched for age, sex, ward, length of stay and
      comorbidity to identify any antibiotic risk factors using conditional logistic
      regression analysis. Environmental sampling on wards was performed with
      cycloserine-cefoxitin-egg yolk agar. Forty-five percent C.difficile isolates
      ribotyped as 027, 39% as 106 and 10% as 001. All ribotypes were resistant to
      ciprofloxacin, erythromycin and cefotaxime but remained susceptible to
      metronidazole and vancomycin. The crude (death within 28 days) and early (death
      within 72h) mortalities were 23% and 11% for the 027 strain, whereas for the 106
      ribotype they were 11% and 3%, respectively. The case-control study identified
      ciprofloxacin usage for >7 days as a significant risk factor (adjusted odds
      ratios of 3.72; 95% CI: 1.38-10.02; P=0.019). Environmental sampling revealed the
      presence of spores on faecally contaminated equipment such as commodes and bedpan
      shells, which persisted after cleaning. Ciprofloxacin appears to encourage
      C.difficile-associated diarrhoea and should be restricted to short courses.
      Cleaning agents for clinical equipment must have sporicidal activity to prevent
      cross-transmission.

PMID- 19386382
TI  - Exercise moderates age-related atrophy of the medial temporal lobe.
AB  - Regional deterioration of brain structure is a typical feature of aging, but
      emerging evidence suggests that exercise may mitigate the decline. The purpose of
      the present investigation was to examine the moderating influence of exercise
      engagement on cross-sectional estimates of age-related brain atrophy at both
      global and regional levels. Estimates of exercise engagement over the past 10
      years and MRI-based measures of global (gray and white) and regional volumes were
      obtained in a sample of 52 healthy older adults aged 55-79. Volume estimates were
      obtained in prefrontal, parietal, temporal, occipital, neostriatal, and medial
      temporal regions. Higher levels of exercise engagement were related to larger
      superior frontal volumes. Most critically, exercise engagement selectively
      moderated age-related medial temporal lobe atrophy. Specifically, significant age
      related atrophy was observed for older adults who engaged in low levels of
      exercise, but not for those who engaged in high levels of exercise. This novel
      finding extends support for the efficacy of exercise to the potential maintenance
      of medial temporal lobe integrity in older adults.

PMID- 19386383
TI  - A Multiple Indicators Multiple Causes (MIMIC) model of Behavioural and
      Psychological Symptoms in Dementia (BPSD).
AB  - INTRODUCTION: Although there is evidence for distinct behavioural sub-phenotypes
      in Alzheimer's disease (AD), their inter-relationships and the effect of clinical
      variables on their expression have been little investigated. METHODS: We have
      analysed a sample of 1850 probable AD patients from the UK and Greece with 10
      item Neuropsychiatric Inventory (NPI) data. We applied a Multiple Indicators
      Multiple Causes (MIMIC) approach to investigate the effect of MMSE, disease
      duration, gender, age and age of onset on the structure of a four-factor model
      consisting of "psychosis", "moods", "agitation" and "behavioural dyscontrol".
      RESULTS: Specific clinical variables predicted the expression of individual
      factors. When the inter-relationship of factors is modelled, some previously
      significant associations are lost. For example, lower MMSE scores predict
      psychosis, agitation and behavioural dyscontrol factors, but psychosis and mood
      predict the agitation factor. Taking these associations into account MMSE scores
      did not predict agitation. CONCLUSIONS: The complexity of the inter-relations
      between symptoms, factors and clinical variables is efficiently captured by this
      MIMIC model.

PMID- 19386384
TI  - Anti-inflammatory drugs reduce age-related decreases in brain volume in
      cognitively normal older adults.
AB  - Previous studies have indicated a decreased risk for developing Alzheimer's
      disease in anti-inflammatory (AI) drug users. Yet few studies have determined
      whether AI drug use provides a protective effect against normal age-related
      changes in the brains of older adults. Regional volume changes in gray and white
      matter were assessed cross-sectionally using optimized voxel-based morphometry in
      36 females taking AI drugs as arthritis or pain medication and 36 age- and
      education-matched female controls. Although mean gray and white matter volume
      differences between AI drug users and the non-AI group were small, AI drug use
      interacted with age, such that the non-AI group showed significantly greater age
      related volume changes in regions of both gray and white matter compared to the
      AI drug users. These regions included the superior and medial frontal gyri,
      middle and inferior temporal gyri, fusiform and parahippocampal gyri, and
      occipital gray matter as well as temporal, parietal, and midbrain white matter.
      The results are consistent with the notion that AI drugs provide protection
      against age-related changes in brain volume. It is possible that inflammation
      plays a role in volume decreases associated with normal aging, and that
      suppressing the inflammatory response moderates this decrease.

PMID- 19386385
TI  - [Epidemic risk of disease associated with a new strain of Clostridium difficile].
AB  - The incidence of Clostridium difficile infection in North America and Europe has
      increased in the last years, generating concern among health professionals. A new
      strain of C. difficile has been identified in recent nosocomial outbreaks and
      community-acquired infections. This new strain, characterized as toxigenic type
      III, PCR ribotype 027 (C. difficile 027), presents higher pathogenicity because
      of increased exotoxin production, and a characteristic antibiotic resistance
      profile. Since 2003, several European countries have notified cases of C.
      difficile 027-associated disease, a fact that demonstrates its rapid
      dissemination. In this article, we review the latest nosocomial outbreaks
      associated with this new strain, which illustrate the need for a standardized
      surveillance system for early detection and implementation of control measures
      aimed at reducing the spread of this microorganism.

PMID- 19386386
TI  - [An HIV-positive man with spontaneous development of a thyroid tumor].

PMID- 19386387
TI  - [Tuberculous pericarditis: an unusual presentation of a common disease].

PMID- 19386388
TI  - [Changes in nosocomial infection control: new challenges and responsibilities for
      the infection control nurse].
AB  - The complexity of surveillance, prevention, and control of nosocomial infections
      has increased over the last decades, owing to reductions in the length of
      hospital stay, health care practice outside of the hospital (home care, day
      hospital care, long-term care facilities, nursing homes), the increase in the
      number of elderly patients, new and emerging diseases, multidrug-resistant
      pathogens, and the administrative requirements for accreditation. In this
      setting, infection control nurses are progressively assuming new responsibilities
      in addition to infection control, such as ensuring the safety of the patient,
      guaranteeing health care quality, and other tasks. In the light of these changes,
      professional organizations of infection control personnel have voiced the opinion
      that staffing for infection control work should not be based solely on the number
      of hospital beds, but also on the complexity of the tasks involved, which should
      be defined according to standardized criteria and infection control indicators.
      In addition, the cost-benefit relationship of infection control programs should
      be demonstrated.

PMID- 19386389
TI  - [Comparative study of the in vitro activity of tigecycline against multiresistant
      Enterococcus faecium isolates].

PMID- 19386390
TI  - Hematogenous spondylitis due to Aspergillus fumigatus in a patient with acquired
      immunodeficiency syndrome.

PMID- 19386391
TI  - [Treatment of respiratory infection by Pseudomonas aeruginosa in adult patients
      within a hospital at home service: clinical characteristics and analysis of
      prognostic factors for relapse].
AB  - INTRODUCTION: Pseudomonas aeruginosa respiratory infections are associated with
      poor respiratory function, low quality of life, and a high relapse rate. METHODS:
      A 6-year prospective study (2000-2005) was carried out. Patients with P.
      aeruginosa respiratory infection admitted to a Hospital at Home service for
      parenteral antibiotic treatment were enrolled in the study. Clinical response to
      treatment, relapse, and relapse-free time, were analyzed as primary endpoints.
      RESULTS: A total of 111 episodes were recorded in 81 patients. Bronchiectasia was
      the most common associated disease (57%). Ceftazidime and tobramycin were the
      first-line therapies used (61%). The average length of stay was 14 days. Among
      the total, 80% of patients had severe/very severe respiratory obstruction, and
      35% were culture-positive at the end of treatment. Median follow-up to relapse
      was 144 days; 65% of episodes relapsed. Relapse was associated with
      bronchiectasia, aerosol therapy, and more severe respiratory obstruction. In the
      patients with severe/very severe obstruction, there was a decrease in relapse
      free time from 1080 to 139 days, in those with positive culture at the end of
      therapy from 248 to 78 days, and in those with resistance to any antipseudomonal
      antibiotic, from 390 to 97 days. On multivariate analysis, severity of
      respiratory obstruction and the antibiotic resistance were independent risk
      factors for relapse. CONCLUSION: Patients infected by P. aeruginosa in poor
      clinical condition or showing resistance to any antipseudomonal antibiotics have
      a higher probability of relapse, and a shorter time to relapse than other
      patients with this infection. The Hospital at Home Service is a good approach to
      reducing the long-term hospital stay in these patients.

PMID- 19386392
TI  - Nosocomial outbreak by imipenem-resistant metallo-beta-lactamase-producing
      Pseudomonas aeruginosa in an adult intensive care unit in a Brazilian teaching
      hospital.
AB  - OBJECTIVE: To describe an outbreak of imipenem-resistant metallo-beta-lactamase
      producing Pseudomonas aeruginosa, enzyme type bla, by horizontal transmission in
      patients admitted to a mixed adult ICU. METHODS: A case-control study was carried
      out, including 47 patients (cases) and 122 patients (control) admitted to the
      mixed ICU of a university hospital in Minas Gerais, Brazil from November 2003 to
      July 2005. The infection site, risk factors, mortality, antibiotic
      susceptibility, metallo-beta-lactamase (MBL) production, enzyme type, and clonal
      diversity were analyzed. RESULTS: A temporal/spatial relationship was detected in
      most patients (94%), overall mortality was 55.3%, and pneumonia was the
      predominant infection (85%). The majority of isolates (95%) were resistant to
      imipenem and other antibiotics, except for polymyxin, and showed MBL production
      (76.7%). Only bla SPM-1 (33%) was identified in the 15 specimens analyzed. In
      addition, 4 clones were identified, with a predominance of clone A (61.5%) and B
      (23.1%). On multivariate analysis, advanced age, mechanical ventilation,
      tracheostomy, and previous imipenem use were significant risk factors for
      imipenem-resistant P. aeruginosa infection. CONCLUSIONS: Clonal dissemination of
      MBL-producing P. aeruginosa strains with a spatial/temporal relationship
      disclosed problems in the practice of hospital infection control, low adherence
      to hand hygiene, and empirical antibiotic use.

PMID- 19386393
TI  - [Impact of 7-valent pneumococcal conjugate vaccination in a population with low
      to intermediate vaccination levels].
AB  - OBJECTIVE: To analyze the changes occurring in declared cases (microbiological
      report) of invasive pneumococcal disease (IPD) in children <2 years old in
      Catalonia (Spain) after the 7-valent pneumococcal conjugate vaccine (PCV7) was
      licensed for use. MATERIAL AND METHODS: Cases of IPD in children <2 years old
      were obtained from notifications to the Microbiological Reporting System of
      Catalonia (MRSC) in 1997-1999 and 2002-2004 by the hospitals (n=23) that have
      participated in the MRSC continuously and uninterruptedly since its inception in
      1995. RESULTS: Overall reported rates were 49.2 cases per 100,000 persons-year in
      1997-1999 and 40.4 per 100,000 persons-year in 2002-2004; the difference was not
      statistically significant. The rate of bacteremic pneumonia fell from 25.2 per
      100,000 persons-year in 1997-1999 to 21.6 per 100,000 persons-year in 2002-2004,
      and meningitis from 6.0 to 4.3 per 100,000 persons-year; again, differences were
      not statistically significant (P>0.05). CONCLUSIONS: After PCV7 was licensed for
      use, a noticeable, but non-significant, reduction in reported IPD rates in
      children <2 years old occurred in Catalonia. If the results had been
      statistically significant, the overall reduction would have been 17.90%, not far
      below the theoretically expected reduction (22%), based on the protective
      efficacy of PCV7 (89%), the percentage of invasive disease-causing serotypes
      included in the vaccine (70%), and the vaccination coverage achieved during the
      study period (35%).

PMID- 19386394
TI  - [Sepsis, psoas abscess and septic arthritis of the hip caused by Yersinia
      enterocolitica].

PMID- 19386395
TI  - [False-negative result with the rapid diagnostic test in Plasmodium ovale
      infection].

PMID- 19386396
TI  - Photochemical electrocyclisation of 3-vinylindoles to pyrido[2,3-a]-, pyrido[4,3
      a]- and thieno[2,3-a]-carbazoles: design, synthesis, DNA binding and antitumor
      cell cytotoxicity.
AB  - In the context of the design and synthesis of DNA ligands, some new hetarene
      annelated carbazoles were synthesized. As lead structure the intercalating
      tetracyclic systems pyrido[2,3-a]- and pyrido[4,3-a]-carbazoles and in one case a
      thieno[2,3-a]-carbazole were taken into account. A dialkyl amino amidic chain was
      introduced to the planar chromophoric system with the intent to generate minor
      groove binding properties. The cytotoxicity of some compounds was examined by the
      NCI antitumor screening. Furthermore, biophysical as well as biochemical studies
      were performed in order to get some information about the DNA-binding properties
      and inhibition of DNA related functional enzymes of this new series of molecules.

PMID- 19386397
TI  - A new type of five-membered heterocyclic inhibitors of basic
      metallocarboxypeptidases.
AB  - A structure-based virtual screening survey was used to identify potential
      inhibitors of the human M14 family of metallocarboxypeptidases. A good
      correlation between docking energy scores and measured K(i) values was observed,
      indicating an efficient performance of the screening procedure. Among various
      compounds displaying K(i) values in the low micromolar range, N-(3-chlorophenyl)
      4-((5-(3-methoxybenzylthio)-1,3,4-oxadiazol-2-yl)methyl)thiazol-2-amine emerged
      as the most powerful inhibitor for human carboxypeptidase B (CPB). According to
      molecular docking, this compound fits into CPB active site cleft through
      coordination of the catalytic zinc ion with the 1,3,4-oxadiazole moiety. This
      represents a novel five-membered heterocyclic type of inhibitor for disease
      linked metallocarboxypeptidases and an interesting lead for further development.

PMID- 19386398
TI  - Dopamine- and tyramine-based derivatives of triazenes: activation by tyrosinase
      and implications for prodrug design.
AB  - A range of triazene derivatives were synthesized and investigated as prodrug
      candidates for melanocyte-directed enzyme prodrug therapy (MDEPT). The prodrugs
      contained a tyramine or dopamine promoiety required for tyrosinase activation and
      this was joined via a urea functional group to the cytotoxic triazene. The
      stability of each of the prodrugs in phosphate buffer, human plasma and in
      mushroom tyrosinase is discussed. The identification of the main peak formed
      after the tyrosinase reaction was attempted by LC-MS and the conversion of
      prodrug to the quinone was confirmed.

PMID- 19386399
TI  - Dry olive leaf extract ameliorates experimental autoimmune encephalomyelitis.
AB  - BACKGROUND & AIMS: Experimental autoimmune encephalomyelitis (EAE) is an animal
      model of CNS inflammatory and demyelinating disease multiple sclerosis.
      Mediterranean diet, rich in olive products is associated with lower incidence of
      multiple sclerosis in South European population. Therefore, the influence of dry
      olive leaf extract (DOLE) on EAE course was investigated. METHODS: Spinal cord
      homogenate and complete Freund's adjuvant were used for the induction of EAE in
      Dark Agouti rats. DOLE was applied intragastrically once per day, starting from
      the day of the immunization. Real time PCR and ELISA were used for the
      determination of IFN-gamma and IL-17 gene expression and production,
      respectively. RESULTS: DOLE reduced various parameters of EAE severity in DA
      rats, including cumulative disease index, maximal clinical score and disease
      duration. Also, DOLE decreased cellularity of the draining lymph nodes and
      production of IFN-gamma and IL-17 by the cells infiltrating spinal cord of EAE
      rats. CONCLUSIONS: The results presented in this paper strongly suggest that DOLE
      enriched diet has a beneficial effect in EAE in rats. Further studies in humans
      are required in order to investigate if DOLE could be a useful supplementary
      dietetic for the patients suffering from multiple sclerosis and other
      neuroinflammatory disorders.

PMID- 19386400
TI  - 137Cs in a raised bog in central Sweden.
AB  - The vertical distribution of (137)Cs activity in peat soil profiles and (137)Cs
      activity concentration in plants of various species was studied in samples
      collected at two sites on a raised bog in central Sweden. One site (open bog) was
      in an area with no trees and only a few sparsely growing plant species, while the
      other (low pine) was less than 100 m from the open bog site and had slowly
      growing Scots pine, a field layer dominated by some ericaceous plants and ground
      well-covered by plants. The plant samples were collected in 2004-2007 and were
      compared with samples collected in 1989 from the same open bog and low pine
      sites. Ground deposition of (137)Cs in 2005 was similar at both sites, 23,000 Bq
      m(-2). In the open bog peat profile it seems to be an upward transport of caesium
      since a clear peak of (137)Cs activity was found in the uppermost 1-4 cm of
      Sphagnum layers, whereas at the low pine site (137)Cs was mainly found in deeper
      (10-12 cm) layers. The migration rate was 0.57 cm yr(-1) at the open bog site and
      the migration centre of (137)Cs was at a depth of 10.7, while the rate at the low
      pine site was 0.78 cm yr(-1) and the migration centre was at 14.9 cm. Heather
      (Calluna vulgaris) was the plant species with the highest (137)Cs activity
      concentrations at both sites, 43.5 k Bq(-1) DM in 1989 decreasing to 20.4 in 2004
      2007 on open bog and 22.3 k Bq kg(-1) DM in 1989 decreasing to 11.2 k Bq(-1) DM
      by the period 2004-2007 on the low pine site. (137)Cs transfer factors in plants
      varied between 0.88 and 1.35 on the open bog and between 0.48 and 0.69 m(2)kg(-1)
      DM at the low pine site.

PMID- 19386401
TI  - Parotid pleomorphic adenoma with solitary renal metastasis.
AB  - We present a rare case of renal metastasis of a recurrent pleomorphic adenoma of
      the parotid gland in an elderly woman. Metastasising pleomorphic adenoma shows
      malignant clinical behaviour, and although it appears histologically benign,
      there may be unknown molecular features that determine its unusual ability to
      spread.

PMID- 19386402
TI  - Women's experiences of group antenatal care in Australia--the CenteringPregnancy
      Pilot Study.
AB  - OBJECTIVE: to describe the experiences of women who were participants in the
      Australian CenteringPregnancy Pilot Study. CenteringPregnancy is an innovative
      model of care where antenatal care is provided in a group environment. The aim of
      the pilot study was to determine whether it would be feasible to implement this
      model of care in Australia. DESIGN: a descriptive study was conducted. Data
      included clinical information from hospital records, and antenatal and postnatal
      questionnaires. SETTING: two metropolitan hospitals in Sydney, Australia.
      PARTICIPANTS: 35 women were recruited to the study and 33 ultimately received all
      their antenatal care (eight sessions) through five[CH(1)] CenteringPregnancy
      groups. FINDINGS: difficulties with recruitment within a short study timeline
      resulted in only 35 (20%) of 171 women who were offered group antenatal care
      choosing to participate. Most women chose this form of antenatal care in order to
      build friendships and support networks. Attendance rates were high and women
      appreciated the opportunity and time to build supportive relationships through
      sharing knowledge, ideas and experiences with other women and with midwives
      facilitating the groups. The opportunity for partners to attend was identified as
      important. Clinical outcomes for women were in keeping with those for women
      receiving standard care; however, the numbers were small. CONCLUSION: the high
      satisfaction of the women suggests that CenteringPregnancy is an appropriate
      model of care for many women in Australian settings, particularly if recruitment
      strategies are addressed and women's partners can participate. IMPLICATIONS FOR
      PRACTICE: CenteringPregnancy group antenatal care assists women with the
      development of social support networks and is an acceptable way in which to
      provide antenatal care in an Australian setting. Recruitment strategies should
      include ensuring that practitioners are confident in explaining the advantages of
      group antenatal care to women in early pregnancy. Further research needs to be
      conducted to implement this model of care more widely.

PMID- 19386403
TI  - Biomechanics of walking with silicone prosthesis after midtarsal (Chopart)
      disarticulation.
AB  - BACKGROUND: Currently accepted understanding is that silicone foot prostheses
      have little influence on biomechanics of walking; however clinical observations
      suggest several beneficial effects. The objective of this study was to
      characterize biomechanics of gait in a group of subjects with disarticulation
      through the talonavicular (T-N) and calcaneocuboid (C-C) (midtarsal) joints
      wearing two different prosthetic solutions: silicone prostheses and conventional
      prostheses. METHODS: Four subjects that underwent Chopart partial foot amputation
      were included in the study. Silicone prosthesis was custom manufactured for each
      individual subject. Instrumented gait analysis was performed in each subject in
      four experimental conditions: barefooted, barefooted and wearing silicon
      prosthesis, wearing footwear with conventional prosthesis and wearing footwear
      with silicon prosthesis. Comparisons and statistical analysis were made between
      both barefooted conditions and both foot-wearing conditions. FINDINGS: Our
      results show that silicone prosthesis without reinforced sole increases gait
      velocity, improves generation of ankle plantarflexion moment throughout the
      stance phase and enables greater power generation at push-off. The most important
      changes, however, occur in the frontal plane, where improved hip adduction angles
      and higher hip abduction moment in the stance enable more normal pelvic movement
      and consequently also less trunk inclination toward amputated side.
      INTERPRETATION: We conclude that silicone prostheses are not solely for cosmetic
      reasons but may be also biomechanically superior over other prosthetic solutions,
      especially for walking barefoot.

PMID- 19386404
TI  - Differential protection of ethylenediurea (EDU) against ambient ozone for five
      cultivars of tropical wheat.
AB  - The antiozonant EDU (ethylenediurea) was used to assess the impact of ambient
      O(3) under field conditions on five cultivars of tropical wheat (Triticum
      aestivum L.). EDU solution (0 ppm and 400 ppm) was applied as soil drench (100 ml
      plant(-1)) 10 days after germination (DAG) at an interval of 12 days. EDU-treated
      plants showed significant increments in stomatal conductance, photosynthetic
      rate, variable fluorescence, total chlorophyll, ascorbic acid, proline and
      protein contents and protective enzymes (POX, SOD and APX) activities in HUW468,
      HUW510 and HUW234 cultivars, while, a reverse trend was observed for lipid
      peroxidation. EDU application restored grain yield significantly by maintaining
      higher levels of antioxidants, metabolites and enzymes in cultivars HUW468 and
      HUW510. Sonalika and PBW343 showed least response of measured parameters under
      EDU treatment suggesting their greater resistance to O(3). EDU, thus proved its
      usefulness in screening suitable wheat cultivars for areas experiencing elevated
      concentrations of O(3).

PMID- 19386405
TI  - An investigation on the physical, chemical and ecotoxicological characteristics
      of particulate matter emitted from light-duty vehicles.
AB  - Particulate matter (PM) emitted from three light-duty vehicles was studied in
      terms of its physicochemical and ecotoxicological character using Microtox
      bioassay tests. A diesel vehicle equipped with an oxidation catalyst emitted PM
      which consisted of carbon species at over 97%. PM from a diesel vehicle with a
      particle filter (DPF) consisted of almost equal amounts of carbon species and
      ions, while a gasoline vehicle emitted PM consisting of approximately 90% carbon
      and approximately 10% ions. Both the DPF and the gasoline vehicles produced a
      distinct nucleation mode at 120 km/h. The PM emitted from the DPF and the
      gasoline vehicles was less ecotoxic than that of conventional diesel, but not in
      direct proportion to the emission levels of the different vehicles. These results
      indicate that PM emission reductions are not equally translated into ecotoxicity
      reductions, implying some deficiencies on the actual environmental impact of
      emission control technologies and regulations.

PMID- 19386406
TI  - Differences in the self-reported racism experiences of US-born and foreign-born
      Black pregnant women.
AB  - Differential exposure to minority status stressors may help explain differences
      in United States (US)-born and foreign-born Black women's birth outcomes. We
      explored self-reports of racism recorded in a survey of 185 US-born and 114
      foreign-born Black pregnant women enrolled in Project Viva, a prospective cohort
      study of pregnant women in Boston, Massachusetts, USA. Self-reported prevalence
      of personal racism and group racism was significantly higher among US-born than
      foreign-born Black pregnant women, with US-born women having 4.1 and 7.8 times
      the odds, respectively, of childhood exposure. In multivariate analyses, US-born
      women's personal and group racism exposure also was more pervasive across the
      eight life domains we queried. Examined by immigrant subgroups, US-born women
      were more similar in their self-reports of racism to foreign-born women who moved
      to the US before age 18 than to women who immigrated after age 18. Moreover, US
      born women more closely resembled foreign-born women from the Caribbean than
      those from Africa. Differential exposure to self-reported racism over the life
      course may be a critically important factor that distinguishes US-born Black
      women from their foreign-born counterparts.

PMID- 19386407
TI  - Primary school children are able to perform basic life-saving first aid measures.
AB  - INTRODUCTION: First aid measures can be life-saving. Starting first aid education
      early may strengthen interest, motivation and ability to provide first aid.
      OBJECTIVE: To determine if a first aid teaching program including 5 lessons (45
      min each) of theoretical and practical training for 6-7-year-old children can
      influence their performance in a first aid scenario. METHODS: 228 primary school
      children at the age of 6-7 years were included in the study, 102 girls and 126
      boys. One child was 5 years old. 117 children were taught basic first aid
      measures and 111 without training served as control group. In the test scenario
      the children had to provide first aid to an unconscious victim after a cycle
      accident. The course participants were retested after 6 months. RESULTS:
      Statistically significant differences between course participants compared to
      those without training could be shown for all tested subjects, including correct
      assessment of consciousness (p<0.001), correct assessment of breathing (p<0.001),
      knowledge of the correct emergency telephone number (p<0.001), giving correct
      emergency call information (p<0.001), knowledge of correct recovery position
      (p<0.001), correct airway management (p<0.001). Retesting after 6 months showed
      statistically significant differences for 5 of 6 tested items. CONCLUSION: 6-7
      Year-old children can give basic first aid to an unconscious patient. A course
      with 5 lessons leads to a significant increase in first aid knowledge and skills.
      Knowledge retention is good after 6 months. All primary school children should
      receive first aid training starting in first grade.

PMID- 19386408
TI  - Outcome measures utilized in clinical trials of interventions for post-cardiac
      arrest syndrome: a systematic review.
AB  - BACKGROUND: The post-cardiac arrest syndrome (period of critical illness
      following return of spontaneous circulation [ROSC]) is a promising window of
      opportunity for clinical trials of therapeutic interventions to improve outcome
      from cardiac arrest. However, the methodological rigor of post-ROSC trials and
      the ability to compare or pool data on treatment effects across studies requires
      consistent and appropriate outcome measures. We aimed to determine the current
      degree of uniformity of outcome measures in clinical trials of post-ROSC
      interventions. METHODS: We conducted a systematic review of Cochrane Library,
      MEDLINE, EMBASE, CINAHL, conference proceedings, and clinical trial registrations
      using a comprehensive strategy. We identified experimental or quasi-experimental
      trials testing post-ROSC interventions in adults. Four authors independently
      extracted data and assessed study quality using standardized instruments.
      RESULTS: The search yielded 33 potential studies, of which 13 randomized
      controlled trials (n=1937) were included in the final analysis. Seven trials
      tested pharmacologic therapies and six tested non-pharmacologic therapies. Our
      main finding is that heterogeneity in the selection and reporting of outcomes
      limited comparability of results across studies. No two trials used exactly the
      same primary outcome, and timing of measurement varied widely. We found only two
      commonalities: (1) indices of functional survival were used rather than survival
      alone, and (2) ordinal scales of neurological function were collapsed into
      clinically meaningful groups ("good" versus "bad" outcome). CONCLUSION: Currently
      there is a lack of uniformity in selection and reporting of outcome measures
      among trials of post-ROSC interventions. Achieving consensus would be an
      important advance for resuscitation science.

PMID- 19386409
TI  - Fetal volume and crown-rump length from 7 to 10 weeks of gestational age in
      singletons and twins.
AB  - OBJECTIVE(S): We intend to verify if fetal volume and crown-rump length were
      different between singletons and twins in pregnancies aged from 7 to 10 weeks and
      to evaluate if fetal volume is more accurate to determine the gestational age
      than crown-rump length at this gestational age. STUDY DESIGN: From 52 days (7
      weeks and 3 days) to 73 days (10 weeks and 3 days) weekly three-dimensional
      ultrasonography was performed in 20 twin fetuses and 20 singletons. Crown-rump
      length and fetal volume using VOCAL were assessed in all examinations. The 'true'
      gestational age was based on oocyte retrieval. RESULTS: At the age of 52 days,
      the crown-rump length was 11.74+/-0.27 mm (mean+/-S.D.) and 11.48+/-0.22 mm
      (singletons and twins, respectively), while the fetal volume was 0.354+/-0.015
      cm(3) and 0.324+/-0.012 cm(3). At the gestational age of 73 days, the crown-rump
      length was 36.19+/-0.90 mm and 35.87+/-0.54 mm and the fetal volume was 6.204+/
      0.090 cm(3) and 6.083+/-0.081 cm(3). The total relative increase observed was
      much higher for fetal volume than for CRL: 1705+/-301% vs. 210+/-33% in
      singletons and 1827+/-305% vs. 214+/-25% in twins. The 95% limits of agreement
      (+/-2.3 days vs.+/-3.2 days, fetal volume vs. crown-rump length) and the
      intraclass correlation coefficients (0.989 vs. 0.978) between the "true"
      gestational age and that predicted by fetal volume were better than those
      predicted by crown-rump length. No significant difference was identified between
      singletons and twins for both fetal volume and crown-rump length. CONCLUSION(S):
      Twins and singletons had similar fetal volume and crown-rump length between the
      7th and 10th week of gestational age. Additionally, fetal volume assessed by
      VOCAL was better than crown-rump length to estimate the gestational age at the
      evaluated period. However, the improvement was small and probably without
      clinical significance. CONDENSATION: Fetal volume and crown-rump length were
      similar between singletons and twins. Fetal volume relative increase was higher
      and the predicted gestational age was better.

PMID- 19386410
TI  - Info-gap theory and robust design of surveillance for invasive species: the case
      study of Barrow Island.
AB  - Surveillance for invasive non-indigenous species (NIS) is an integral part of a
      quarantine system. Estimating the efficiency of a surveillance strategy relies on
      many uncertain parameters estimated by experts, such as the efficiency of its
      components in face of the specific NIS, the ability of the NIS to inhabit
      different environments, and so on. Due to the importance of detecting an invasive
      NIS within a critical period of time, it is crucial that these uncertainties be
      accounted for in the design of the surveillance system. We formulate a detection
      model that takes into account, in addition to structured sampling for incursive
      NIS, incidental detection by untrained workers. We use info-gap theory for
      satisficing (not minimizing) the probability of detection, while at the same time
      maximizing the robustness to uncertainty. We demonstrate the trade-off between
      robustness to uncertainty, and an increase in the required probability of
      detection. An empirical example based on the detection of Pheidole megacephala on
      Barrow Island demonstrates the use of info-gap analysis to select a surveillance
      strategy.

PMID- 19386411
TI  - Production of lightweight aggregates from mining and industrial wastes.
AB  - Washing aggregate sludge from a gravel pit, sewage sludge from a wastewater
      treatment plant (WWTP) and a clay-rich sediment have been physically, chemically
      and mineralogically characterized. They were mixed, milled and formed into
      pellets, pre-heated for 5 min and sintered in a rotary kiln at 1150 degrees C,
      1175 degrees C, 1200 degrees C and 1225 degrees C for 10 and 15 min at each
      temperature. The effects of the raw material characteristics, heating
      temperatures and dwell times on the loss on ignition (LOI), bloating index (BI),
      bulk density (rho(b)), apparent and dry particle densities (rho(a), rho(d)),
      voids (H), water absorption (WA(24h)) and compressive strength (S) were
      determined. All the mixtures presented a bloating potential taking into
      consideration the gases released at high temperatures. The products obtained were
      lightweight aggregates (LWAs) in accordance with Standard UNE-EN-13055-1
      (rho(b)<or=1.20 g/cm(3) or particle density<or=2.00 g/cm(3)). LWAs manufactured
      with 50% washing aggregate sludge and 50% clay-rich sediment were expanded LWAs
      (BI>0) and showed the lowest apparent particle density, the lowest water
      absorption and the highest compressive strength. It was possible to establish
      three groups of LWAs on the basis of their properties in comparison to Arlita G3,
      F3 and F5, commercially available lightweight aggregates manufactured in Spain.
      Our LWAs may have the same or similar applications as these commercial products,
      such as horticulture, prefabricated lightweight structures and building
      structures.

PMID- 19386412
TI  - Partially pyrolyzed olive pomace sorbent of high permeability for
      preconcentration of metals from environmental waters.
AB  - The aim of this work is to develop a preconcentration procedure of Cd(2+), Zn(2+)
      and Cu(2+) in environmental waters using olive pomace (OP) prior to their
      determination by flame atomic absorption spectrometry (FAAS). Raw OP as
      preconcentrating sorbent was found to have low permeability towards the passed
      water samples and thus long time was needed. Even reducing the vacuum pressure
      caused cartridge blockage. Novel preconcentrating sorbents of high permeability
      were then prepared by heat pretreatment under inert atmosphere (partial
      pyrolysis) of OP at various temperatures (100, 150, 200, 250 and 300 degrees C).
      The permeability of OP pyrolyzed at 200 degrees C (sorbent OP-200) was enhanced
      11 times relative to the raw OP, which significantly reduced the time required in
      the preconcentration process. A preconcentration procedure was optimized using OP
      200 as preconcentrating sorbent, in which the detection limits were 42 ng L(-1)
      for Cu(2+), 76 ng L(-1) for Zn(2+) and 172 ng mL(-1) for Cd(2+). The method was
      linear within the studied concentration range (2-100 ng mL(-1)). The proposed
      method gave recoveries from 83+/-6 to 103+/-5% for determination of metals in tap
      water; and recoveries from 81+/-6 to 100+/-6% in well water. The method was
      validated by comparison with independent method and by analysis of lake sediments
      LKSD-4 certified reference material.

PMID- 19386413
TI  - Kinetics, equilibrium and mechanism of Cd2+ removal from aqueous solution by
      mungbean husk.
AB  - Mungbean husk (mbh), an agrowaste material, was investigated as a new sorbent for
      the removal of Cd(2+) from aqueous solution. The maximum removal of Cd(2+) was
      found to be 35.41 mg g(-1) at pH 5.0, 500 mg l(-1) initial Cd(2+) concentration
      and 5 g l(-1) sorbent dosage. Sorption kinetics and equilibria followed pseudo
      second order and Langmuir isotherm equations. The mechanism of Cd(2+) adsorption
      on mbh was investigated by DRIFT spectroscopy, SEM-EDX analysis, and by
      monitoring the release of alkali and alkaline earth metal cations (Ca(2+),
      Mg(2+), K(+) and Na(+)) during the uptake of Cd(2+). DRIFT spectra of mbh showed
      the presence of amino, carboxyl, carbonyl and hydroxyl as the major functional
      groups involved in the sorption of Cd(2+). The sum of Ca(2+), Mg(2+), Na(+) and
      K(+) released from mbh with the quantitatively equivalent uptake of Cd(2+)
      indicated that the main mechanism of Cd(2+) adsorption was ion exchange. EDX
      analysis data supported the hypothesis of the involvement of ion exchange, as
      alkali and alkaline earth metal cations were noted to disappear in EDX spectrum
      of mbh after the uptake of Cd(2+). No significant loss in Cd(2+) sorption
      capacity of regenerated mbh was noted during reuse for five successive sorption
      desorption cycles.

PMID- 19386414
TI  - A QSPR model for estimation of lower flammability limit temperature of pure
      compounds based on molecular structure.
AB  - In this study, a quantitative structure-property relationship was presented to
      estimate lower flammability limit temperature (LFLT) of pure compounds. This
      relationship is a multi-linear equation and has six parameters. These chemical
      structure-based parameters were selected from 1664 molecular-based parameters by
      genetic algorithm multivariate linear regression (GA-MLR). Since 1171 compounds
      were used to develop this equation, the model can be used to estimate the LFLT of
      a wide range of pure compounds.

PMID- 19386415
TI  - An assembled poly-4-vinyl pyridine and cellulose triacetate membrane and Bi2S3
      electrode for photoelectrochemical diffusion of metallic ions.
AB  - The transport phenomena across ion exchange membrane may be enhanced by applying
      various strengths inside or outside the system. The electrical current, generated
      by n-type semiconductor, is used to catalyse the separation of metal ions. The
      cation exchange membrane located between the two compartments allows both the
      separation and concentration of M(n+) (Ag(+), Cu(2+), Pb(2+) and Ni(2+)). The
      flows of M(n+) from the aqueous solution to-and inside the membrane are monitored
      by the determination of the fluxes and the potentials. In this study, the four
      cations are investigated alone or in quaternary systems. From
      photoelectrochemical measurement, the gap of Bi(2)S(3) is found to be indirect at
      1.65 eV. The shape of photocurrent potential curve and the negative flat band
      potential (-1.02 V(SCE)) give evidence of n-type character. The conduction band (
      1.25 V(SCE)) yields thermodynamically M(2+) photoreduction and catalyzes the
      diffusion process. The photoelectrode Bi(2)S(3) makes the flux twofold greater
      than that observed in the dark. In all cases, the potential of the electrode
      M(2+)/M in the feed compartment increases until a maximal value, reached at
      approximately 100 min above which it undergoes a diminution. The membrane is more
      selective to Cu(2+) and this selectivity decreases in the quaternary system.

PMID- 19386417
TI  - Effect of the pH in the adsorption and in the immersion enthalpy of
      monohydroxylated phenols from aqueous solutions on activated carbons.
AB  - An activated carbon Carbochem--PS230 was modified by chemical and thermal
      treatment in flow of H(2) in order to evaluate the influence of the activated
      carbon chemical surface in the adsorption of the monohydroxylated phenols. The
      solid-solution interaction was determined by analyzing the adsorption isotherms
      at 298 K at pH 7, 9 and 11 during 48 h. The adsorption capacity of activated
      carbons increases when the pH solution decreases. The amount adsorbed increases
      in the reduced carbon at the maximum adsorption pH and decreases in the oxidized
      carbon. In the sample of granulated activated carbon, CAG, the monohydroxylated
      phenols adsorption capacity diminishes in the following order catechol
      >hydroquinone >resorcinol, at the three pH values. The experimental data are
      evaluated with Freundlich's and Langmuir's models. The immersion enthalpies are
      determined and increase with the retained amount, ranging between 21.5 and 45.7 J
      g(-1). In addition, the immersion enthalpies show more interaction with the
      reduced activated carbon that has lower total acidity contents.

PMID- 19386416
TI  - Mercury(II) and methyl mercury speciation on Streptococcus pyogenes loaded Dowex
      Optipore SD-2.
AB  - A solid phase extraction procedure based on speciation of mercury(II) and methyl
      mercury on Streptococcus pyogenes immobilized on Dowex Optipore SD-2 has been
      established. Selective and sequential elution with 0.1 mol L(-1) HCl for methyl
      mercury and 2 mol L(-1) HCl for mercury(II) were performed at pH 8. The
      determination of mercury levels was performed by cold vapour atomic absorption
      spectrometry (CVAAS). Optimal analytical conditions including pH, amounts of
      biosorbent, sample volumes, etc., were investigated. The influences of the some
      alkaline and earth alkaline ions and some transition metals on the recoveries
      were also investigated. The capacity of biosorbent for mercury(II) and methyl
      mercury was 4.8 and 3.4 mg g(-1). The detection limit (3 sigma) of the reagent
      blank for mercury(II) and methyl mercury was 2.1 and 1.5 ng L(-1).
      Preconcentration factor was calculated as 25. The relative standard deviations of
      the procedure were below 7%. The validation of the presented procedure is
      performed by the analysis of standard reference material (NRCC-DORM 2 Dogfish
      Muscle). The procedure was successfully applied to the speciation of mercury(II)
      and methyl mercury in natural water and environmental samples.

PMID- 19386418
TI  - Removal of copper(II) from aqueous solution by pine and base modified pine cone
      powder as biosorbent.
AB  - Pine cone, a popular agricultural waste in South Africa has been studied for its
      potential application as a biosorbent in its raw and sodium hydroxide modified
      form. Surface modification were carried out using sodium hydroxide solution of
      concentration ranging from 0.01 to 0.15 mol L(-1)and the samples characterized.
      Batch kinetics were carried out on the biosorption of copper(II) from aqueous
      solution using the prepared samples and varying biosorption parameters such as
      solution pH, dose and biosorption temperature. The results revealed that pine
      cone surface was modified by sodium hydroxide treatment, carboxylic and phenolic
      functional groups were mostly affected as seen from Boehm's titration and FTIR
      analysis. Surface modification reduced pH(PZC) from 7.49 to 2.55 and also
      increased the internal surface of pine cone powder. Copper(II) biosorption
      studies revealed that optimum solution pH and biosorbent dose for copper(II)
      removal was pH 5 and 8.0g L(-1), for the untreated and treated samples.
      Copper(II) uptake followed the pseudo-second order kinetic model and the
      intraparticle diffusion model. Copper(II) removal increased with NaOH
      modification and higher NaOH concentration. Biosorption temperature was found to
      increase copper(II) uptake for all samples indicating that copper(II) biosorption
      is endothermic in nature. Activation energy computed from the pseudo-second order
      rate constant increased with NaOH modification from 18.22 to 21.39 kJ mol(-1).
      The thermodynamic parameters of activation (DeltaG*, DeltaH* and DeltaS*) were
      computed using Erying equation and the results show that the reorientation step
      is mostly entropy controlled at the activation state and the contribution of
      entropy to the reorientation step of activation tends to decrease with NaOH
      washing and with increase in NaOH concentration.

PMID- 19386419
TI  - Refinement of the 200 structure factor for GaAs using parallel and convergent
      beam electron nanodiffraction data.
AB  - We present a new method to measure structure factors from electron spot
      diffraction patterns recorded under almost parallel illumination in transmission
      electron microscopes. Bloch wave refinement routines have been developed to
      refine the crystal thickness, its orientation and structure factors by comparison
      of experimentally recorded and calculated intensities. Our method requires a
      modicum of computational effort, making it suitable for contemporary personal
      computers. Frozen lattice and Bloch wave simulations of GaAs diffraction patterns
      are used to derive optimised experimental conditions. Systematic errors are
      estimated from the application of the method to simulated diffraction patterns
      and rules for the recognition of physically reasonable initial refinement
      conditions are derived. The method is applied to the measurement of the 200
      structure factor for GaAs. We found that the influence of inelastically scattered
      electrons is negligible. Additionally, we measured the 200 structure factor from
      zero loss filtered two-dimensional convergent beam electron diffraction patterns.
      The precision of both methods is found to be comparable and the results agree
      well with each other. A deviation of more than 20% from isolated atom scattering
      data is observed, whereas close agreement is found with structure factors
      obtained from density functional theory [A. Rosenauer, M. Schowalter, F. Glas, D.
      Lamoen, Phys. Rev. B 72 (2005), 085326-1], which account for the redistribution
      of electrons due to chemical bonding via modified atomic scattering amplitudes.

PMID- 19386420
TI  - Selection of appropriate serological tests to measure the incidence of natural
      Leishmania infantum infection during DNA/MVA prime/boost canine vaccine trials.
AB  - In response to the increasing need for field trials of experimental DNA vaccines
      against zoonotic visceral leishmaniasis in dogs, our aim was to validate the use
      of ELISA protocols which will be suitable for detection of natural infection in
      vaccinated dogs. We have previously demonstrated that DNA/modified vaccinia virus
      Ankara (MVA) vaccine expressing tryparedoxin peroxidase (TRYP) induced high
      titres of TRYP antigen-specific IgG in immunized dogs. Here we report our
      findings that seroconversion to an unrelated diagnostic antigen rK39 did not
      occur in vaccinated dogs, and that responses to crude Leishmania infantum
      promastigote antigen (CLA) were weak and short-lived. This is in contrast to
      strong responses to both antigens shown in naturally infected dogs. To select an
      appropriate serological test for measurement of infection incidence, we also
      tested longitudinal samples from an immunologically well-characterized cohort of
      naturally infected dogs. The sensitivity of CLA ELISA was superior to that of
      rK39 in early stage infection (from 2 months before, to 2 months after the first
      detection of infection by PCR or parasitological culture), and more sensitive
      than rK39 in cross-sectional sampling (81.0% vs 61.9%). We conclude that CLA
      ELISA will provide sensitive estimates of L. infantum infection incidence in
      DNA/MVA vaccinated dogs, though optimal testing would include rK39, or a similar
      recombinant antigen, to improve overall specificity.

PMID- 19386421
TI  - Sex differences in hormonal responses to a social stressor in chronic major
      depression.
AB  - BACKGROUND: Acute depression has been associated with increased hypothalamic
      pituitary-adrenal (HPA) reactivity. While chronicity of depressive illness
      influences symptoms, course and outcome, its effect on the HPA axis has not been
      extensively evaluated. The current study evaluated cortisol stress responses to a
      social challenge in chronic major depressive disorder (CMDD). METHODS: Cortisol
      stress responses to the Trier Social Stress Test (TSST) were compared in 26
      participants with CMDD and 28 healthy controls using repeated measures analysis
      of variance (RANOVA). In addition, group differences in area under the curve
      (AUC) and peak percentage change in cortisol were examined. RESULTS: The RANOVA
      indicated a significant sex by condition interaction in cortisol responses to the
      social challenge. Post-hoc testing of pair-wise group differences revealed that
      in females, CMDD subjects had greater cortisol levels in response to the TSST
      than did controls. Similarly, AUC was greater in females with CMDD than in female
      controls. Neither of these differences was significant in males. However, male
      CMDD subjects exhibited a significantly decreased peak percentage change in
      cortisol in response to the TSST than did male controls. CONCLUSIONS: Males and
      females with CMDD exhibited unique differences in cortisol responses to the
      social challenge relative to controls. In females, CMDD subjects had greater
      overall secretion of cortisol whereas in males, CMDD subjects had a blunted peak
      response to the social stressor. Sex differences are an important consideration
      in future work in this population.

PMID- 19386422
TI  - Understanding comorbidity between substance use, anxiety and affective disorders:
      broadening the research base.
AB  - In this paper, we argue that the research base for understanding comorbidity
      between substance use and other mental disorders needs to be broadened. We
      specifically advocate for: 1) more prospective epidemiological studies of
      relationships between alcohol and other drug use disorders and anxiety and mood
      disorders; 2) greater use of twin study designs to disentangle shared genetic and
      environmental contributions to comorbidity; 3) prospective neuroimaging studies
      of the effects of early and sustained alcohol and drug use on the developing
      adolescent brain; 4) a greater focus on the effects on comorbidity of primary and
      secondary prevention interventions for substance use, anxiety, affective and
      conduct disorders among children and adolescents; and 5) better evaluations of
      the impact of treatment upon persons with comorbid substance use and other mental
      disorders.

PMID- 19386423
TI  - Dosimetric comparison of three different involved nodal irradiation techniques
      for stage II Hodgkin's lymphoma patients: conventional radiotherapy, intensity
      modulated radiotherapy, and three-dimensional proton radiotherapy.
AB  - PURPOSE: To compare the dose distribution to targeted and nontargeted tissues in
      Hodgkin's lymphoma patients using conventional radiotherapy (CRT), intensity
      modulated RT (IMRT), and three-dimensional proton RT (3D-PRT). METHODS AND
      MATERIALS: CRT, IMRT, and 3D-PRT treatment plans delivering 30 cobalt Gray
      equivalent (CGE)/Gy to an involved nodal field were created for 9 Stage II
      Hodgkin's lymphoma patients (n = 27 plans). The dosimetric endpoints were
      compared. RESULTS: The planning target volume was adequately treated using all
      three techniques. The IMRT plan produced the most conformal high-dose
      distribution; however, the 3D-PRT plan delivered the lowest mean dose to
      nontarget tissues, including the breast, lung, and total body. The relative
      reduction in the absolute lung volume receiving doses of 4-16 CGE/Gy for 3D-PRT
      compared with CRT ranged from 26% to 37% (p < .05), and the relative reduction in
      the absolute lung volume receiving doses of 4-10 CGE/Gy for 3D-PRT compared with
      IMRT was 48-65% (p < .05). The relative reduction in absolute total body volume
      receiving 4-30 CGE/Gy for 3D-PRT compared with CRT was 47% (p < .05). The
      relative reduction in absolute total body volume receiving a dose of 4 CGE/Gy for
      3D-PRT compared with IMRT was 63% (p = .03). The mean dose to the breast was
      significantly less for 3D-PRT than for either IMRT or CRT (p = .03) The mean dose
      and absolute volume receiving 4-30 CGE/Gy for the heart, thyroid, and salivary
      glands were similar for the three modalities. CONCLUSION: In this favorable
      subset of Hodgkin's lymphoma patients without disease in or below the hila, 3D
      PRT significantly reduced the dose to the breast, lung, and total body. These
      observed dosimetric advantages might improve the clinical outcomes of Hodgkin's
      lymphoma patients by reducing the risk of late radiation effects related to low
      to-moderate doses in nontargeted tissues.

PMID- 19386424
TI  - PET/CT for radiotherapy treatment planning in patients with soft tissue sarcomas.
AB  - PURPOSE: To study the possibility of incorporating positron emission
      tomography/computed tomography (PET/CT) information into radiotherapy treatment
      planning in patients with high-grade soft tissue sarcomas (STS). METHODS AND
      MATERIALS: We studied 17 patients treated with preoperative radiotherapy at our
      institution from 2005 to 2007. All patients had a high-grade STS and had had a
      staging PET/CT scan. For each patient, an MRI-based gross tumor volume (GTV),
      considered to be the contemporary standard for radiotherapy treatment planning,
      was outlined on a T1-gadolinium enhanced axial MRI (GTV(MRI)), and a second set
      of GTVs were outlined using different threshold values on PET images (GTV(PET)).
      PET-based target volumes were compared with the MRI-based GTV. Threshold values
      for target contouring were determined as a multiple (from 2 to 10 times) of the
      background soft tissue uptake values (B) sampled over healthy tissue. RESULTS:
      PET-based GTVs contoured using a threshold value of 2 or 2.5 most closely
      resembled the GTV(MRI) volumes. Higher threshold values lead to PET volumes much
      smaller than the GTV(MRI). The standard deviations between the average volumes of
      GTV(PET) and GTV(MRI) ratios for all thresholds were large, ranging from 36% for
      2 xB up to 93% for 10 xB. Maximum uptake-to-background ratio correlated poorly
      with the maximum standardized uptake values. CONCLUSIONS: It is unlikely that
      PET/CT will make a significant contribution in GTV definition for radiotherapy
      treatment planning in patients with STS using threshold methods on PET images.
      Future studies will focus on molecular imaging and tumor physiology.

PMID- 19386425
TI  - Postoperative radiotherapy in the management of resected non-small-cell lung
      carcinoma: 10 years' experience in a single institute.
AB  - PURPOSE: This study reports the long term outcomes of postoperative radiotherapy
      in patients with resection for non-small-cell lung cancer (NSCLC). METHODS AND
      MATERIALS: A total of 98 patients with resected NSCLC who received postoperative
      radiotherapy (PORT) between January 1994 and December 2004 were retrospectively
      analyzed. The most frequently performed surgical procedure was lobectomy (59
      patients), followed by pneumonectomy (25), wedge resection (8), and bilobectomy
      (6). Postoperative radiotherapy was delivered as an adjuvant treatment in 71
      patients, after a wedge resection in 8 patients, and after an R1 resection in 19
      patients. The PORT was administered using a Co-60 source in 86 patients and 6-MV
      photons in 12 patients. A Kaplan-Meier estimate of overall survival, locoregional
      control, and distant metastasis-free survival were calculated. RESULTS: Stages
      included I (n =13), II (n = 50), IIIA (n = 29), and IIIB (n = 6). After a median
      follow-up of 52 months median survival was 61 months. The 5-year overall
      survival, locoregional control, and distant metastasis-free survival rates for
      the whole group were 50%, 78%, and 55% respectively. The RT dose, Karnofsky
      performance status, age, lateralization of the tumor, and pneumonectomy were
      independent prognostic factors for OAS; anemia and the number of involved lymph
      nodes were independent prognostic factors for LC. CONCLUSIONS: Doses of PORT of
      greater than 54 Gy were associated with higher death rate in patients with left
      sided tumor, which may indicate a risk of radiation-induced cardiac mortality.

PMID- 19386426
TI  - Factors predictive of tumor recurrence and survival after initial complete
      response of esophageal squamous cell carcinoma to definitive chemoradiotherapy.
AB  - PURPOSE: To assess factors predictive of recurrent disease and survival after
      achieving initial complete response (CR) to chemoradiotherapy (CRT) for
      esophageal cancer. METHODS AND MATERIALS: Patients who had clinical Stage I-IVA
      esophageal cancer and received definitive CRT between 2001 and 2007 were
      retrospectively analyzed. RESULTS: Of 269 patients with esophageal cancer, 110
      who achieved CR after definitive CRT were included in the analyses.
      Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with
      concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences
      and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates
      were 18% and 32%, respectively. By univariate and multivariate analyses, tumor
      category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p =
      0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9;
      95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4;
      p = 0.004) were independent risk factors for regional lymph node or distant
      recurrences. The cumulative overall 1- and 3-year survival rates were 91% and
      66%, respectively. As expected, recurrence was associated with poor survival (p =
      0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8;
      95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4;
      p = 0.018) were independent factors predictive of survival after recurrence.
      CONCLUSION: Risk of recurrence after definitive CRT for esophageal cancer was
      associated with tumor category, age, and primary tumor location; this information
      may help in improved prognostication for these patients.

PMID- 19386427
TI  - Hypofractionated intensity-modulated arc therapy for lymph node metastasized
      prostate cancer.
AB  - PURPOSE: To determine the planning results and acute toxicity after
      hypofractionated intensity-modulated arc radiotherapy and androgen deprivation
      for lymph node metastasized (Stage N1) prostate cancer. METHODS AND MATERIALS: A
      total of 31 patients with Stage T1-T4N1M0 prostate cancer were treated with
      intensity-modulated arc radiotherapy and 3 years of androgen deprivation as
      primary treatment. The clinical target volume (CTV(p)) was the prostate and
      seminal vesicles. Elective lymph node areas ((e)) were delineated and expanded by
      2 mm to create the CTV(e). The planning target volumes (PTV(p) and PTV(e)) were
      created using a three-dimensional expansion of the CTV(p) and CTV(e),
      respectively, of 7 mm. A median dose of 69.3 Gy and 50 Gy was prescribed to the
      PTV(p) and PTV(e) respectively, to be delivered in 25 fractions. Upper and lower
      gastrointestinal toxicity was scored using the Radiation Therapy Oncology Group
      toxicity and radiotherapy-induced lower intestinal toxicity scoring system.
      Genitourinary toxicity was scored using a combined Radiation Therapy Oncology
      Group, LENT-SOMA (late effects normal tissue-subjective, objective, management,
      analytic), and Common Toxicity Criteria toxicity scoring system. RESULTS: The
      median follow-up time was 3 months. The mean prescription dose to the CTV(p) and
      PTV(p) was 70.4 Gy and 68.6 Gy, respectively. The minimal dose to the CTV(e) and
      PTV(e) was 49.0 Gy and 47.0 Gy, respectively. No acute Grade 2 or greater
      gastrointestinal toxicity occurred. Fourteen patients developed acute Grade 2
      lower gastrointestinal toxicity. Acute Grade 3 and 2 genitourinary toxicity
      developed in 2 and 14 patients, respectively. CONCLUSION: The results of our
      study have shown that hypofractionated intensity-modulated arc radiotherapy as
      primary therapy for N1 prostate cancer is feasible with low toxicity.

PMID- 19386428
TI  - Robotic stereotactic radioablation concomitant with neo-adjuvant chemotherapy for
      breast tumors.
AB  - PURPOSE: Robotic stereotactic radioablation (RSR) allows stereotactic irradiation
      of thoracic tumors; however, it has never been used for breast tumors and may
      have a real potential. We conducted a Phase I study, including neoadjuvant
      chemotherapy (NACT), a two-level dose-escalation study (6.5 Gy x 3 fractions and
      7.5 Gy x 3 fractions) using RSR and breast-conserving surgery followed by
      conventional radiotherapy. MATERIALS AND METHODS: To define toxicity, we
      performed a dermatologic exam (DE) including clinical examination by two
      independent observers and technical examination by colorimetry, dermoscopy, and
      skin ultrasound. DE was performed before NACT (DE0), at 36 days (DE1), at 56 days
      (DE2), after the NACT treatment onset, and before surgery (DE3). Surgery was
      performed 4-8 weeks after the last chemotherapy session. A pathologic examination
      was also performed. RESULTS: There were two clinical complete responses and four
      clinical partial responses at D56 and D85. Maximum tolerable dose was not
      reached. All patients tolerated RSR with no fatigue; 2 patients presented with
      mild pain after the third fraction of the treatment. There was no significant
      toxicity measured with ultrasound and dermoscopy tests. Postoperative irradiation
      (50 Gy) has been delivered without toxicity. CONCLUSION: The study showed the
      feasibility of irradiation with RSR combined with chemotherapy and surgery for
      breast tumors. There was no skin toxicity at a dose of 19.5 Gy or 22.5 Gy
      delivered in three fractions combined with chemotherapy. Lack of toxicity
      suggested that the dose could be increased further. Pathologic response was
      acceptable.

PMID- 19386429
TI  - Stereotactic radiotherapy for intracranial nonacoustic schwannomas including
      facial nerve schwannoma.
AB  - PURPOSE: Although the effectiveness of stereotactic radiosurgery for nonacoustic
      schwannomas is currently being assessed, there have been few studies on the
      efficacy of stereotactic radiotherapy (SRT) for these tumors. We investigated the
      long-term outcome of SRT for nonacoustic intracranial nerve schwannomas. METHODS
      AND MATERIALS: Seventeen patients were treated between July 1994 and December
      2006. Of these patients, 7 had schwannomas located in the jugular foramen, 5 in
      the trigeminal nerve, 4 in the facial nerve, and 1 in the oculomotor nerve.
      Radiotherapy was used as an initial treatment without surgery in 10 patients
      (59%) and after initial subtotal resection in the remaining patients. The tumor
      volume ranged from 0.3 to 31.3 mL (mean, 8.2 mL). The treatment dose was 40 to 54
      Gy in 20 to 26 fractions. The median follow-up period was 59.5 months (range, 7.4
      122.6 months). Local control was defined as stable or decreased tumor size on
      follow-up magnetic resonance imaging. RESULTS: Tumor size was decreased in 3
      patients, stable in 13, and increased in 1 after SRT. Regarding neurologic
      symptoms, 8 patients (47%) had improvement and 9 patients were unchanged. One
      patient had an increase in tumor size and received microsurgical resection at 32
      months after irradiation. No patient had worsening of pre-existing neurologic
      symptoms or development of new cranial nerve deficits at the last follow-up.
      CONCLUSIONS: SRT is an effective alternative to surgical resection for patients
      with nonacoustic intracranial nerve schwannomas with respect to not only long
      term local tumor control but also neuro-functional preservation.

PMID- 19386430
TI  - Concomitant chemoradiotherapy using carboplatin, tegafur-uracil and leucovorin
      for stage III and IV head-and-neck cancer: results of GORTEC Phase II study.
AB  - PURPOSE: Concomitant chemoradiotherapy is the standard treatment of locally
      advanced, nonresectable, head-and-neck squamous cell carcinoma. However, the
      optimal chemotherapy regimen is still controversial. The objective of this Phase
      II study was to evaluate the feasibility and efficacy of a concomitant treatment
      using tegafur-uracil, leucovorin, carboplatin, and radiotherapy. METHODS AND
      MATERIALS: A total of 77 patients with head-and-neck squamous cell carcinoma
      Stage III and IVA were enrolled between October 2003 and July 2005. Of the 77
      patients, 72 were eligible. They were treated with tegafur-uracil (300 mg/m(2)/d)
      and leucovorin (75 mg/d) from Days 1 to 19 and from Days 29 to 47 and carboplatin
      (70 mg/m(2) intravenously for 4 consecutive days), in three cycles every 21 days.
      Conventional radiotherapy was delivered to a total dose of 70 Gy in 35 fractions.
      RESULTS: With a mean follow-up of 22.8 months, the 3-year locoregional control,
      overall survival and disease-free survival actuarial rate was 33.1%, 41.9%, and
      27.2%, respectively. The compliance of the treatment was correct. The main acute
      toxicity was mucositis, with 62% Grade 3-4. Three patients (4.2%) died of acute
      toxicity. The incidence and severity of late toxicity was acceptable, with 32%
      Grade 3 and no Grade 4 toxicity. CONCLUSION: The protocol of concomitant
      chemoradiotherapy using tegafur-uracil, leucovorin, and carboplatin for locally
      advanced unresectable head-and-neck squamous cell carcinoma is feasible. The
      compliance was correct. The incidence and severity of the acute and late
      toxicities were acceptable, but not improved. The efficacy of this regimen seems
      equivalent to the main protocols of concurrent chemoradiotherapy. It represents a
      possible alternative for patients without an intravenous catheter.

PMID- 19386431
TI  - Treatment of nasopharyngeal carcinoma using intensity-modulated radiotherapy-the
      national cancer centre singapore experience.
AB  - PURPOSE: The aim of this study was to determine the efficacy and acute toxicity
      of our early experience with treating nasopharyngeal carcinoma (NPC) patients
      with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A review was
      conducted on case records of 195 patients with histologically proven,
      nonmetastatic NPC treated with IMRT between 2002 and 2005. MRI of the head and
      neck was fused with CT simulation images. All plans had target volumes at three
      dose levels, with a prescribed dose of 70 Gy to the gross disease, in 2.0-2.12
      Gy/fraction over 33-35 fractions. Cisplatin-based chemotherapy was offered to
      Stage III/IV patients. RESULTS: Median patient age was 52 years, and 69% were
      male. Median follow-up was 36.5 months. One hundred and twenty-three patients had
      Stage III/IV disease (63%); 50 (26%) had T4 disease. One hundred and eighty-eight
      (96%) had complete response; 7 (4%) had partial response. Of the complete
      responders, 10 (5.3%) had local recurrence, giving a 3-year local recurrence-free
      survival estimate of 93.1% and a 3-year disease-free survival of 82.1%. Fifty-one
      patients (26%) had at least one Grade 3 toxicity. CONCLUSIONS: Results from our
      series are comparable to those reported by other centers. Acute toxicity is
      common. Local failure or persistent disease, especially in patients with bulky T4
      disease, are issues that must be addressed in future trials.

PMID- 19386432
TI  - Clinical-pathologic features and long-term outcomes of tubular carcinoma of the
      breast compared with invasive ductal carcinoma treated with breast conservation
      therapy.
AB  - PURPOSE: To evaluate our institutional experience of treating tubular carcinoma
      of the breast (TC) and invasive ductal carcinoma (IDC) with conservative surgery
      and radiation therapy, to compare clinical-pathologic features and long-term
      outcomes. METHODS AND MATERIALS: A review of our institution's tumor registry
      from 1975 to 2007, followed by a central pathology review of available slides,
      yielded 71 cases of Stage I/II TC and 2,238 cases of Stage I/II IDC treated with
      breast conservation therapy. Clinical-pathologic features and outcomes were
      analyzed by subtype to detect significant differences. RESULTS: The median follow
      up was 7 years. The TC cohort presented more frequently with pT1 disease (97% vs.
      80%, p = 0.0007), pN0 disease (95% vs. 74%, p = 0.0004), hormone-receptor
      positivity (ER+, 89% vs. 62%, p = 0.0001; PR+, 81% vs. 52%, p = 0.0001), and HER
      2 negativity (89% vs. 71%, p = 0.04). Clinical outcomes also favored the TC
      cohort, with lower rates of breast cancer-related death (1% vs. 10%; p = 0.0109)
      and distant metastasis (1% vs. 13%; p = 0.0028) and higher rates of 10-year
      overall (90% vs. 80%; p = 0.033), cause-specific (99% vs. 86%; p = 0.011), and
      disease-free (99% vs. 82%; p = 0.003) survival. There was a nonsignificant trend
      toward improved breast cancer relapse-free survival for the TC cohort (95% vs.
      87%; p = 0.062) but no difference in nodal relapse-free survival or contralateral
      breast cancer relapse-free survival (all p values >0.05) between the cohorts.
      CONCLUSION: Our institutional experience suggests that TC, when compared with
      IDC, is associated with more favorable clinical-pathologic features and
      comparable, if not superior, outcomes after breast conservation therapy,
      suggesting the appropriateness of a conservative approach to this rare subtype.

PMID- 19386434
TI  - Frequency distribution of second solid cancer locations in relation to the
      irradiated volume among 115 patients treated for childhood cancer.
AB  - PURPOSE: To provide better estimates of the frequency distribution of second
      malignant neoplasm (SMN) sites in relation to previous irradiated volumes, and
      better estimates of the doses delivered to these sites during radiotherapy (RT)
      of the first malignant neoplasm (FMN). METHODS AND MATERIALS: The study focused
      on 115 patients who developed a solid SMN among a cohort of 4581 individuals. The
      homemade software package Dos_EG was used to estimate the radiation doses
      delivered to SMN sites during RT of the FMN. Three-dimensional geometry was used
      to evaluate the distances between the irradiated volume, for RT delivered to each
      FMN, and the site of the subsequent SMN. RESULTS: The spatial distribution of SMN
      relative to the irradiated volumes in our cohort was as follows: 12% in the
      central area of the irradiated volume, which corresponds to the planning target
      volume (PTV), 66% in the beam-bordering region (i.e., the area surrounding the
      PTV), and 22% in regions located more than 5 cm from the irradiated volume. At
      the SMN site, all dose levels ranging from almost zero to >75 Gy were
      represented. A peak SMN frequency of approximately 31% was identified in volumes
      that received <2.5 Gy. CONCLUSION: A greater volume of tissues receives low or
      intermediate doses in regions bordering the irradiated volume with modern
      multiple-beam RT arrangements. These results should be considered for risk
      benefit evaluations of RT.

PMID- 19386433
TI  - A prognostic index for predicting lymph node metastasis in minor salivary gland
      cancer.
AB  - PURPOSE: Large studies examining the clinical and pathological factors associated
      with nodal metastasis in minor salivary gland cancer are lacking in the
      literature. METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End
      Results (SEER) database, we identified 2,667 minor salivary gland cancers with
      known lymph node status from 1988 to 2004. Univariate and multivariate analyses
      were conducted to identify factors associated with the use of neck dissection,
      the use of external beam radiation therapy, and the presence of cervical lymph
      node metastases. RESULTS: Four hundred twenty-six (16.0%) patients had neck nodal
      involvement. Factors associated with neck nodal involvement on univariate
      analysis included increasing age, male sex, increasing tumor size, high tumor
      grade, T3-T4 stage, adenocarcinoma or mucoepidermoid carcinomas, and pharyngeal
      site of primary malignancy. On multivariate analysis, four statistically
      significant factors were identified, including male sex, T3-T4 stage, pharyngeal
      site of primary malignancy, and high-grade adenocarcinoma or high-grade
      mucoepidermoid carcinomas. The proportions (and 95% confidence intervals) of
      patients with lymph node involvement for those with 0, 1, 2, 3, and 4 of these
      prognostic factors were 0.02 (0.01-0.03), 0.09 (0.07-0.11), 0.17 (0.14-0.21),
      0.41 (0.33-0.49), and 0.70 (0.54-0.85), respectively. Grade was a significant
      predictor of metastasis for adenocarcinoma and mucoepidermoid carcinoma but not
      for adenoid cystic carcinoma. CONCLUSIONS: A prognostic index using the four
      clinicopathological factors listed here can effectively differentiate patients
      into risk groups of nodal metastasis. The precision of this index is subject to
      the limitations of SEER data and should be validated in further clinical studies.

PMID- 19386435
TI  - Stereotactic body radiation therapy for liver tumors: impact of daily setup
      corrections and day-to-day anatomic variations on dose in target and organs at
      risk.
AB  - PURPOSE: To assess day-to-day differences between planned and delivered target
      volume (TV) and organ-at-risk (OAR) dose distributions in liver stereotactic body
      radiation therapy (SBRT), and to investigate the dosimetric impact of setup
      corrections. METHODS AND MATERIALS: For 14 patients previously treated with SBRT,
      the planning CT scan and three treatment scans (one for each fraction) were
      included in this study. For each treatment scan, two dose distributions were
      calculated: one using the planned setup for the body frame (no correction), and
      one using the clinically applied (corrected) setup derived from measured tumor
      displacements. Per scan, the two dose distributions were mutually compared, and
      the clinically delivered distribution was compared with planning. Doses were
      recalculated in equivalent 2-Gy fraction doses. Statistical analysis was
      performed with the linear mixed model. RESULTS: With setup corrections, the mean
      loss in TV coverage relative to planning was 1.7%, compared with 6.8% without
      corrections. For calculated equivalent uniform doses, these figures were 2.3% and
      15.5%, respectively. As for the TV, mean deviations of delivered OAR doses from
      planning were small (between -0.4 and +0.3 Gy), but the spread was much larger
      for the OARs. In contrast to the TV, the mean impact of setup corrections on
      realized OAR doses was close to zero, with large positive and negative
      exceptions. CONCLUSIONS: Daily correction of the treatment setup is required to
      obtain adequate TV coverage. Because of day-to-day patient anatomy changes, large
      deviations in OAR doses from planning did occur. On average, setup corrections
      had no impact on these doses. Development of new procedures for image guidance
      and adaptive protocols is warranted.

PMID- 19386436
TI  - Basic fibroblast growth factor-2/beta3 integrin expression profile: signature of
      local progression after chemoradiotherapy for patients with locally advanced non
      small-cell lung cancer.
AB  - PURPOSE: No biologic signature of chemoradiotherapy sensitivity has been reported
      for patients with locally advanced non-small-cell lung cancer (NSCLC). We have
      previously demonstrated that basic fibroblast growth factor (FGF-2) and
      alphavbeta3 integrin pathways control tumor radioresistance. We investigated
      whether the expression of the proteins involved in these pathways might be
      associated with the response to treatment and, therefore, the clinical outcome.
      METHODS AND MATERIALS: FGF-2, beta3 integrin, angiopoietin-2, and syndecan-1
      expression was studied using immunohistochemistry performed on biopsies obtained,
      before any treatment, from 65 patients exclusively treated with chemoradiotherapy
      for locally advanced NSCLC. The response to treatment was evaluated according to
      the Response Evaluation Criteria in Solid Tumors criteria using computed
      tomography at least 6 weeks after the end of the chemoradiotherapy. Local
      progression-free survival, metastasis-free survival, and disease-free survival
      were studied using the log-rank test and Cox proportional hazard analysis.
      RESULTS: Among this NSCLC biopsy population, 43.7% overexpressed beta3 integrin
      (beta3(+)), 43% FGF-2 (FGF-2(+)), 41.5% syndecan-1, and 59.4% angiopoietin-2. Our
      results showed a strong association between FGF-2 and beta3 integrin expression
      (p = .001). The adjusted hazard ratio of local recurrence for FGF-2(+)/beta3(+)
      tumors compared with FGF-2(-)/beta3(-) tumors was 6.1 (95% confidence interval,
      2.6-14.6, p = .005). However, the risk of local recurrence was not increased when
      tumors overexpressed beta3 integrin or FGF-2 alone. Moreover, the co-expression
      of these two proteins was marginally associated with the response to
      chemoradiotherapy and metastasis-free survival. CONCLUSION: The results of this
      study have identified the combined profile FGF-2/beta3 integrin expression as a
      signature of local control in patients treated with chemoradiotherapy for locally
      advanced NSCLC.

PMID- 19386437
TI  - Physician expectations of treatment outcomes for patients with brain metastases
      referred for whole brain radiotherapy.
AB  - PURPOSE: Patients with advanced cancer are referred to our Rapid Response
      Radiotherapy Program for quick access to palliative radiotherapy. The primary
      objective of this prospective study was to determine the physician expectations
      of the treatment outcomes for patients with brain metastases referred for whole
      brain radiotherapy (WBRT). The secondary objectives were to determine the factors
      influencing the expectations and to examine the accuracy of the physician
      estimated patient survival. METHODS AND MATERIALS: Patients were identified
      during a 17-month period. The referring physicians were sent a survey by
      facsimile to be completed and returned before the patient consultation.
      Information was sought on the patient's disease status, the physician's
      expectations of WBRT, the estimated patient survival and performance status, and
      physician demographic data. RESULTS: A total of 137 surveys were sent out, and
      the overall response rate was 57.7%. The median patient age was 66 years (range,
      35-87), 78.5% had multiple brain metastases, 42.3% had a controlled primary
      tumor, and 62.3% had extracranial disease. WBRT was thought to stabilize
      neurologic symptoms, improve quality of life, and allow for a Decadron
      (dexamethasone) taper by > or =94.9% of the referring physicians; 87.0% thought
      WBRT would improve performance status; 77.9% thought it would improve neurologic
      symptoms; and 40.8% thought it would improve survival. The referring physicians
      estimated patient survival as a median of 6.0 months; however, the actual
      survival was a median of 2.5 months, for a median individual difference of 1.9
      months (p < .0001). CONCLUSION: Physicians referring patients with brain
      metastases for consideration of WBRT are often overly optimistic when estimating
      the clinical benefit of the treatment and overestimate patient survival. These
      findings highlight the need for education and additional research in this field.

PMID- 19386438
TI  - Margin on gross tumor volume and risk of local recurrence in head-and-neck
      cancer.
AB  - PURPOSE: To determine whether the method or extent of construction of the high
      dose clinical target volume (CTV) and high-dose planning target volume (PTV) in
      intensity-modulated radiation therapy (IMRT) for head-and-neck cancer are
      associated with an increased risk of locoregional failure. MATERIALS AND METHODS:
      Patients with nasopharyngeal, oropharyngeal, oral cavity, hypopharyngeal, or
      laryngeal squamous cell carcinomas treated definitively with IMRT were included.
      All patients without local relapse had a minimum follow-up of 12 months. Median
      follow-up for all patients was 24 months. Treatment plans of 85 available
      patients were reviewed, and the gross tumor volume (GTV) to PTV expansion method
      was estimated. RESULTS: The GTVs were expanded volumetrically in 71 of 85
      patients, by a median of 15 mm (range, 4-25 mm). An anatomic component to the
      expansion of GTV was used in 14 of 85 patients. Eighteen patients failed
      locoregionally, for an actuarial locoregional control rate of 77.2% at 2 years.
      There was no significant difference in locoregional control between patients with
      GTVs expanded volumetrically vs. those with a component of anatomic expansion. In
      patients with GTVs expanded volumetrically, no increase in risk of local failure
      was seen in patients with a total GTV expansion of < or =15 mm. CONCLUSION: In
      this retrospective study, there was not an increased risk of local failure using
      smaller margins or expanding GTVs volumetrically when treating head-and-neck
      cancer patients definitively with IMRT.

PMID- 19386439
TI  - Early hyperbaric oxygen therapy for reducing radiotherapy side effects: early
      results of a randomized trial in oropharyngeal and nasopharyngeal cancer.
AB  - PURPOSE: Comparison of quality of life (QoL) and side effects in a randomized
      trial for early hyperbaric oxygen therapy (HBOT) after radiotherapy (RT). METHODS
      AND MATERIALS: From 2006, 19 patients with tumor originating from the tonsillar
      fossa and/or soft palate (15), base of tongue (1), and nasopharynx (3) were
      randomized to receive HBOT or not. HBOT consisted of 30 sessions at 2.5 ATA (15
      msw) with oxygen breathing for 90 min daily, 5 days per week, applied shortly
      after the RT treatment was completed. As of 2005, all patients received validated
      questionnaires (i.e., the European Organization for Research and Treatment of
      Cancer [EORTC] QLQ-C30, EORTC QLQ Head and Neck Cancer Module (H&N35),
      Performance Status Scale): before treatment; at the start of RT treatment; after
      46 Gy; at the end of RT treatment; and 2, 4, and 6 weeks and 3, 6, 12, and 18
      months after follow-up. RESULTS: On all QoL items, better scores were obtained in
      patients treated with hyperbaric oxygen. The difference between HBOT vs. non-HBOT
      was significant for all parameters: EORTC H&N35 Swallowing (p = 0.011), EORTC
      H&N35 Dry Mouth (p = 0.009), EORTC H&N35, Sticky Saliva (p = 0.01), PSS Eating in
      Public (p = 0.027), and Pain in Mouth (visual analogue scale; p < 0.0001).
      CONCLUSIONS: Patients randomized for receiving hyperbaric oxygen after the RT had
      better QoL scores for swallowing, sticky saliva, xerostomia, and pain in mouth.

PMID- 19386440
TI  - Locally advanced rectal cancer patients receiving radio-chemotherapy: a novel
      clinical-pathologic score correlates with global outcome.
AB  - PURPOSE: To determine the importance of downstaging of locally advanced rectal
      cancer after neoadjuvant treatment. METHODS AND MATERIALS: The study included all
      consecutive patients with locally advanced rectal cancer who underwent
      neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian
      centers from June 1996 to December 2003. A novel score was used, calculated as
      the sum of numbers obtained by giving a negative or positive point, respectively,
      to each degree of increase or decrease in clinical to pathologic T and N status.
      RESULTS: A total of 317 patients were eligible for analysis. Neoadjuvant
      treatments performed were as follows: radiotherapy alone in 75 of 317 patients
      (23.7%), radiotherapy plus chemotherapy in 242 of 317 patients (76.3%). Worse
      disease-free survival was observed in patients with a lower score (Score 1 = -3
      to +3 vs. Score 2 = +4 to +7; p = 0.04). CONCLUSIONS: Our results suggest that a
      novel score, calculated from preoperative and pathologic tumor and lymph node
      status, could represent an important parameter to predict outcome in patients
      receiving neoadjuvant treatment for rectal cancer. The score could be useful to
      select patients for adjuvant chemotherapy after neoadjuvant treatment and
      surgery.

PMID- 19386441
TI  - Ductal carcinoma in situ of the breast with close or focally involved margins
      following breast-conserving surgery: treatment with reexcision or radiotherapy
      with increased dosage.
AB  - PURPOSE: Following breast-conserving surgery for DCIS, reexcision before
      radiotherapy is recommended when margins are close or involved. We investigated
      whether an additional radiation dose could replace reexcision. METHODS: We
      selected 208 women with DCIS of the breast treated with breast-conserving surgery
      between 1992 and 2002 who had either close margins (< 2 mm) (89 pts) or focally
      (< 1 mm) or minimally (1-15 mm) involved margins (119 pts). Sixty-one patients
      (29%) underwent reexcision before irradiation and 147 patients (71%) received
      breast irradiation with boost, without reexcision. RESULTS: Median follow-up was
      89 months. Median age was 53 years with 7 patients less than 41. Involved margins
      were less frequent in the non reexcision group than in the reexcised group (50%
      vs. 74%, p = 0.0019). All other clinical and histological features were
      comparable. Median whole-breast radiation dose was 50 Gy. Median total doses to
      the tumour bed were 67 Gy (range, 45-77) and 60 Gy (range, 46-74), respectively
      (p < 0.0001). Of the 61 reexcised patients, 56% had residual DCIS and 6% had
      invasive cancer. Six underwent a mastectomy for persistent margin involvement.
      Seven-year locoregional failure rates were 9.3% without, and 9.6% with reexcision
      (ns). No differences were observed when adjusting for margin status. CONCLUSION:
      In carefully selected patients with close (< 2 mm) or focally/minimally involved
      margins, reexcision may be avoided and satisfactory local control achieved by
      increasing the radiation dose to the tumour bed to at least 66 Gy. These results
      only apply to patients older than 40 and would need confirmation in independent
      series.

PMID- 19386442
TI  - Effectiveness and safety of spot scanning proton radiation therapy for chordomas
      and chondrosarcomas of the skull base: first long-term report.
AB  - PURPOSE: To evaluate effectiveness and safety of spot-scanning-based proton
      radiotherapy (PT) in skull-base chordomas and chondrosarcomas. METHODS AND
      MATERIALS: Between October 1998 and November 2005, 64 patients with skull-base
      chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer
      Institute with PT using spot-scanning technique. Median total dose for chordomas
      was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per
      fraction. Local control (LC), disease specific survival (DSS), and overall
      survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v.
      3.0. RESULTS: Mean follow-up period was 38 months (range, 14-92 months). Five
      patients with chordoma and one patient with chondrosarcoma experienced local
      recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for
      chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross
      tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years
      rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for
      chondrosarcomas, respectively. High-grade late toxicity consisted of one patient
      with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two
      patients with Grade 3 central nervous system necrosis. No patient experienced
      brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%.
      CONCLUSIONS: Our data indicate safety and efficacy of spot-scanning based PT for
      skull-base chordomas and chondrosarcomas. With target definition, dose
      prescription and normal organ tolerance levels similar to passive-scattering
      based PT series, complication-free, tumor control and survival rates are at
      present comparable.

PMID- 19386443
TI  - Geometrical sparing factors for the rectum and bladder in the prediction of grade
      2 and higher complications after high-dose-rate brachytherapy for cervical
      cancer.
AB  - PURPOSE: This study aimed to assess the predictive values of geometrical sparing
      factors for the rectum and bladder in high-dose-rate intracavitary brachytherapy
      (HDRICB) for Grade 2 and higher late sequelae in patients with cervical cancer.
      METHODS: A total of 392 patients were enrolled in this study. They were treated
      with external beam radiotherapy to the pelvis, after which HDRICB was performed
      using Ir-192 remote after-loading at 1-week intervals for three or four sessions.
      The geometrical sparing factor (GSF) was defined as the average of the ratios
      between the reference doses and the Point A dose. RESULTS: A total of 46 patients
      (11.7%) had Grade 2 or higher late rectal complications (36 Grade 2, 9 Grade 3,
      and 1 Grade 4). In all, 32 patients (8.2%) had Grade 2 or higher late bladder
      complications (14 Grade 2, 16 Grade 3, and 2 Grade 4). Multivariate analysis
      demonstrated a high risk of rectal sequelae in patients who developed bladder
      complications (p = 0.0004, hazard ratio 3.54) and had a rectal GSF greater than
      0.7 (p = 0.01, hazard ratio 1.99). The high risk factors for bladder
      complications were development of rectal complications (p = 0.0004, hazard ratio
      3.74), concurrent chemotherapy (p = 0.0001, relative risk 3.94), and a bladder
      GSF greater than 0.9 (p = 0.01, hazard ratio, 2.53). CONCLUSION: This study
      demonstrates the predictive value of GSFs in HDRICB for cervical cancer. Patients
      with rectal GSFs greater than 0.7 or bladder GSFs greater than 0.9 are at risk
      for Grade 2 and higher late sequelae.

PMID- 19386444
TI  - Imaging cellular proliferation during chemo-radiotherapy: a pilot study of serial
      18F-FLT positron emission tomography/computed tomography imaging for non-small
      cell lung cancer.
AB  - PURPOSE: To establish whether (18)F-3'-deoxy-3'-fluoro-L-thymidine ((18)F-FLT)
      can monitor changes in cellular proliferation of non-small-cell lung cancer
      (NSCLC) during radical chemo-radiotherapy (chemo-RT). METHODS AND MATERIALS: As
      part of a prospective pilot study, 5 patients with locally advanced NSCLC
      underwent serial (18)F-FLT positron emission tomography (PET)/computed tomography
      (CT) scans during treatment. Baseline (18)F-FLT PET/CT scans were compared with
      routine staging (18)F-FDG PET/CT scans. Two on-treatment (18)F-FLT scans were
      performed for each patient on Days 2, 8, 15 or 29, providing a range of time
      points for response assessment. RESULTS: In all 5 patients, baseline lesional
      uptake of (18)F-FLT on PET/CT corresponded to staging (18)F-FDG PET/CT
      abnormalities. (18)F-FLT uptake in tumor was observed on five of nine (55%) on
      treatment scans, on Days 2, 8 and 29, but not Day 15. A "flare" of (18)F-FLT
      uptake in the primary tumor of one case was observed after 2 Gy of radiation
      (1.22 x baseline). The remaining eight on-treatment scans demonstrated a mean
      reduction in (18)F-FLT tumor uptake of 0.58 x baseline. A marked reduction of
      (18)F-FLT uptake in irradiated bone marrow was observed for all cases. This
      reduction was observed even after only 2 Gy, and all patients demonstrated a
      complete absence of proliferating marrow after 10 Gy. CONCLUSIONS: This proof of
      concept study indicates that (18)F-FLT uptake can monitor the distinctive
      biologic responses of epithelial cancers and highly radiosensitive normal tissue
      changes during radical chemo-RT. Further studies of (18)F-FLT PET/CT imaging
      during therapy may suggest that this tracer is useful in developing response
      adapted RT for NSCLC.

PMID- 19386445
TI  - ACR appropriateness criteria on external beam radiation therapy treatment
      planning for clinically localized prostate cancer expert panel on radiation
      oncology--prostate.

PMID- 19386446
TI  - [Is the stability of results in IVF possible?].
AB  - OBJECTIVES: To evaluate quality control impact, in assisted reproductive
      medecine, in view of the stability of results. MATERIALS AND METHODS: Prospective
      collection of all IVF cycles at the center of AMP at Antoine-Beclere hospital
      (Clamart), as well as pregnancy outcomes, from 2002 till 2006. RESULTS: 44.3% in
      the clinical pregnancy rate and 38.0% in the delivery rate per oocyte retrieval.
      These rates are stable during the five years studied. The rate of multiple
      pregnancy is of 30.7%, decreasing, with the decrease in number of transferred
      embryos. CONCLUSION: Results are stable over five years duration. Quality control
      seems to be necessary.

PMID- 19386447
TI  - [Management of antenatal fetal abdominal tumors. Clues for the diagnosis of a
      congenital mesoblastic nephroma].
AB  - The prenatal diagnosis of abdominal mass poses the problem of its origin. Renal
      tumors are rarer than neuroblastoma but they are most often congenital
      mesoblastic nephroma. The congenital mesoblastic nephroma has a good forecast in
      spite of a sonographic impressive aspect. MRI can help to locate tumor but cannot
      tell difference between the different kinds of renal tumor. Prenatal forecast is
      especially linked with hydramnios and hydrops fetalis. Histolological study of
      the tumor is important for the prognosis. Two morphological subtypes are
      currently distinguished: the classic type with a good forecast and the atypical
      or cellular type. Distant metastases have been related only to the cellular form
      but especially in infants aged more than 3 months and never in the newborns. The
      diagnosis of the tumor does not change the mode of delivery except in case of an
      important volume. Complications are searched during the first days of life:
      hypertension, hypercalcemia, vomiting, hyperreninemia. Radical nephrectomy is
      performed after the end of the first week. In case of a classic form, the healing
      is always obtained. In case of cellular form, distant metastases are searched. In
      any rate, the follow-up is recommended until the end of the growth.

PMID- 19386448
TI  - The harm inside: injection during incarceration among male injection drug users
      in Tijuana, Mexico.
AB  - Limited access to sterile syringes and condoms in correctional facilities make
      these settings high risk environments for HIV transmission. Although
      incarceration among injection drug users (IDUs) is common, there is limited
      information regarding specific IDU risk behaviors inside. We examined correlates
      of incarceration, injection inside and syringe sharing inside among male IDUs
      recruited in Tijuana, Mexico, using respondent driven sampling (RDS) (n=898). An
      interviewer administered survey collected data on sociodemographic, behavioral
      and contextual characteristics. Associations with (a) history of incarceration,
      (b) injection inside, and (c) syringe sharing inside were identified using
      univariate and multiple logistic regression models with RDS adjustment. Seventy
      six percent of IDUs had been incarcerated, of whom 61% injected inside. Three
      quarters (75%) of those who injected shared syringes. U.S. deportation [adjusted
      odds ratio (AOR)=1.61; 95% confidence interval (CI): 1.07, 2.43] and migration
      (AOR=1.81; 95% CI: 1.12, 2.95) were independently associated with incarceration.
      Injection inside was independently associated with recent receptive syringe
      sharing (AOR=2.46; 95% CI: 1.75, 3.45) and having sex with a man while
      incarcerated (AOR=3.59; 95% CI: 1.65, 7.83). Sharing syringes inside was
      independently associated with having sex with a man while incarcerated (AOR=6.18;
      95% CI: 1.78, 21.49). A majority of incarcerated IDUs reported injecting and
      syringe sharing during incarceration, and these IDUs were more likely to engage
      in sex with other men. Corrections-based interventions to reduce injection and
      syringe sharing are urgently needed, as are risk reduction interventions for male
      IDUs who have sex with men while incarcerated.

PMID- 19386449
TI  - Whole-body vibration augments resistance training effects on body composition in
      postmenopausal women.
AB  - Age-related changes in body composition are well-documented with a decrease in
      lean body mass and a redistribution of body fat generally observed. Resistance
      training alone has been shown to have positive effects on body composition,
      however, these benefits may be enhanced by the addition of a vibration stimulus.
      OBJECTIVE: The purpose of this study was to determine the effects of 8 months of
      resistance training with and without whole-body vibration (WBV) on body
      composition in sedentary postmenopausal women. METHODS: Fifty-five women were
      assigned to resistance only (RG, n=22), vibration plus resistance (VR, n=21) or
      non-exercising control (CG, n=12) groups. Resistance training (3 sets 10
      repetitions 80% strength) was performed using isotonic weight training equipment
      and whole-body vibration was done with the use of the power plate (Northbrooke,
      IL) vibration platform for three times per week for 8 months. Total and regional
      body composition was assessed from the total body DXA scans at baseline (pre) and
      after 8 months (post) of training. RESULTS: In the VR group, total % body fat
      decreased from pre- to post-time points (p<0.05), whereas, the CG group had a
      significant increase in total % body fat (p<0.05). Both training groups exhibited
      significant increases in bone free lean tissue mass for the total body, arm and
      trunk regions from pre to post (p<0.05). CG did not show any changes in lean
      tissue. CONCLUSION: In older women, resistance training alone and with whole-body
      vibration resulted in positive body composition changes by increasing lean
      tissue. However, only the combination of resistance training and whole-body
      vibration was effective for decreasing percent body fat.

PMID- 19386451
TI  - Abnormal bleeding in postmenopausal hormone users-What do we know today?
AB  - Whilst use of estrogen-containing hormone therapy (HT) has declined in recent
      years, it is still used by a significant minority of women and remains the most
      effective way of treating menopausal vasomotor symptoms and vaginal dryness.
      Unscheduled vaginal bleeding and spotting is a common unwanted effect of combined
      HT. This abnormal bleeding is inconvenient and commonly leads to invasive tests
      to exclude underlying pelvic pathology. The mechanisms underlying unscheduled
      bleeding with HT are poorly understood and there are no evidence-based treatment
      options. Relatively few studies have investigated how combined hormone therapy
      induces changes in the endometrium which may predispose to increased bleeding.
      The available evidence suggests that combined HT induces changes in endometrial
      blood vessels and stroma which may increase vascular fragility. An improved
      understanding of how combined HT changes the endometrium to induce bleeding may
      lead to targeted therapies to effectively prevent or resolve bleeding in
      postmenopausal women. This will improve the acceptability of combined HT and have
      personal benefits for postmenopausal women and financial benefits for healthcare
      providers. This review will discuss current evidence and potential mechanisms
      underlying unscheduled bleeding with combined HT.

PMID- 19386450
TI  - Comparative effects of risedronate, atorvastatin, estrogen and SERMs on bone mass
      and strength in ovariectomized rats.
AB  - OBJECTIVE: The aim of this study was to investigate bone protective effects of
      risedronate, atorvastatin, raloxifene and clomiphene citrate in ovariectomized
      rats. METHODS: Our study was conducted on 63 rats at Experimental Research Center
      of Celal Bayar University. Six-month-old rats were divided into seven groups.
      There were five drug administered ovariectomized groups, one ovariectomized
      control group without drug administration and one non-ovariectomized control
      group without drug administration. Eight weeks postovariectomy, rats were treated
      with the bisphosphonate risedronate sodium, the statin atorvastatin, the estrogen
      17beta-estradiol and the selective estrogen receptor modulators (SERMs)
      raloxifene hydrochloride and clomiphene citrate by gavage daily for 8 weeks. At
      the end of the study, rats were killed under anesthesia. For densitometric
      evaluation, left femurs and tibiae were removed. Left femurs were also used to
      measure bone volume. Right femurs were used for three-point bending test.
      RESULTS: Compared to ovariectomized group, femur cortex volume increased
      significantly in non-ovariectomized group (p=0.016). Compared to non
      ovariectomized group, distal femoral metaphyseal and femur midshaft bone mineral
      density values were significantly lower in ovariectomized group (p=0.047). In
      ovariectomy+atorvastatin group, whole femur and femur midshaft bone mineral
      density and three-point bending test maximal load values were significantly
      higher than ovariectomized group (p=0.049, 0.05, and 0.018). When compared to the
      ovariectomized group, no significant difference was found with respect to femoral
      maximum load values in groups treated with risedronate, estrogen, raloxifene and
      clomiphene (p=0.602, 0.602, 0.75, and 0.927). In ovariectomy+risedronate group,
      femur midshaft bone mineral density values were significantly higher than the
      values in ovariectomized group (p=0.023). When compared to ovariectomized group,
      no significant difference was found with respect to femur midshaft bone mineral
      density values in groups treated with estrogen, raloxifene and clomiphene
      (p=0.306, 0.808, and 0.095). CONCLUSIONS: While risedronate sodium prevented the
      decrease in bone mineral density in ovariectomized rats, atorvastatin maintained
      mechanical characteristics of bone and also prevented the decrease in bone
      mineral density as risedronate sodium.

PMID- 19386452
TI  - Pattern of injury in child fatalities resulting from child abuse.
AB  - According to the US Department of Health and Human Services, in 2005, an
      estimated 1460 children died of maltreatment. The purpose of this study is to
      further examine the pattern of bony injuries in child maltreatment fatalities,
      with an emphasis on the prevalence of antemortem fractures and the presence of
      associated perimortem fractures. The sample was 162 male and female children. The
      majority of the data were collected from the case files of the NC Child Fatality
      Prevention Team at the Office of the Chief Medical Examiner in Chapel Hill, North
      Carolina (n=152) spanning from 2000 to 2005. An additional 10 cases from 2001 to
      2006 were included from the Charleston County Coroner's Office, Charleston, SC.
      Six age categories were used in this study: 0-3 months, 4-6 months, 7-9 months,
      10-16 months, 17 months to 2 years, and 2-6 years. Lesions were documented and
      categorized into four general body loci: craniofacial, thoraco/abdominal,
      appendicular, and multiple. The peak age categories of death were 0-3 months
      (25%) and 2-6 years (19%), with 50% of deaths occurring in infants 9 months old
      or younger. The body locus most frequently affected was craniofacial.

PMID- 19386453
TI  - Cerebral palsy update.
AB  - A common language on CP has been developed for the European registers by the SCPE
      (Surveillance of Cerebral Palsy in Europe) working group and the common database
      allows prevalence analyses on a larger basis. CP prevalence increases with lower
      birthweight and higher immaturity. Increase of survival after preterm birth has
      first also increased CP rates. But already in the 80s this trend was reversed for
      LBW infants, and in the 90 s also for VLBW or very immature infants. The outcome
      with respect to CP in the group of extremely LBW or immature infants remains a
      matter of specific concern, as prevalence seems to be rather stable on a high
      level. CP is caused in more than 80% by brain lesions or maldevelopments which
      can be attributed to different timing periods of the developing brain. Extent and
      topography determine the clinical subtype of CP and are related also to the
      presence and severity of associated disabilities. CP, thus, offers a model to
      study plasticity of the developing brain. Reorganisation following unilateral
      lesions is mainly interhemispheric and homotopic. In the motor system, it
      involves the recruitment of ipsilateral tracts; functionality seems to be limited
      and decreases already towards the end of gestation. There is no clear evidence
      for substantial reorganisation in the sensory system. The best compensatory
      potential is described concerning language function following left hemispheric
      lesions. Language function reorganized to the right hemisphere eventually seems
      not to be impaired, this occurs, however, on the expense of primary right
      hemispheric functions.

PMID- 19386454
TI  - Review of Alexander disease: beyond the classical concept of leukodystrophy.
AB  - Alexander disease is classified as one of the leukodystrophies, which are
      degenerative diseases primarily affecting the cerebral white matter. Formal
      diagnosis is achieved by showing diffuse accumulation of Rosenthal fibers in the
      brain by biopsy or autopsy. Showing a heterozygous mutation in the glial
      fibrillary acidic protein (GFAP) gene is currently sufficient for diagnosis. The
      mechanisms of Rosenthal fiber formation remain unclear. However, both the quality
      and quantity of GFAP are important. GFAP-epsilon (rodent homologous GFAP-delta),
      one of the alternatively spliced GFAP isoforms, may also play a modulating role
      in aggregate formation. The current ease of diagnosis has accelerated the
      accumulation of a wide variety of patients with Alexander disease along with the
      widespread use of MRI. In contrast to the classical infantile type, patients with
      juvenile and adult types mainly complain of bulbar symptoms and usually show
      progressive atrophy of the lower brainstem and cervical spinal cord with mild or
      minimal leukodystrophic changes. Among the many MRI findings of Alexander
      disease, periventricular linear lesions with various names depending on the
      thickness and shape seem to represent the unique pathophysiology, because the
      subventricular zone of the adult human brain includes special astrocytes that
      behave as multipotent progenitor cells and specifically produce GFAP-epsilon.
      Except for a few mutations, no clear phenotype-genotype correlation has been
      established for Alexander disease, although male preponderance in the infantile
      type suggests that phenotypes may be partly affected by gender.

PMID- 19386455
TI  - Panayiotopoulos syndrome: an important childhood autonomic epilepsy to be
      differentiated from occipital epilepsy and acute non-epileptic disorders.
AB  - Panayiotopoulos syndrome is a common multifocal autonomic childhood epileptic
      disorder with significant clinical, pathophysiological and management
      implications. It affects otherwise normal children with onset at around 3-6
      years. It is characterized by seizures, often prolonged, with predominantly
      autonomic symptoms and mainly ictal vomiting. EEG shows shifting and/or multiple
      foci, often with occipital dominance. Despite characteristic clinical and EEG
      manifestations Panayiotopoulos syndrome is often confused with occipital epilepsy
      and acute non-epileptic disorders such as encephalitis, syncope, cyclic vomiting
      or atypical migraine. This review aims to describe Panayiotopoulos syndrome on
      the basis of independent major studies and provide clinical clues for diagnosis
      and management.

PMID- 19386456
TI  - Corticosteroids for acute adult bacterial meningitis.
AB  - Bacterial meningitis in adults is a severe disease, with high fatality and
      morbidity rates. Experimental studies showed that the inflammatory response in
      the subarachnoid space is associated with unfavorable outcome. In these
      experiments, corticosteroids, and in particular dexamethasone, were able to
      reduce the inflammatory cascades in the subarachnoid space. The use of
      corticosteroids as adjunctive therapy in adults with bacterial meningitis was
      evaluated in eight studies, performed over 45 years. Most studies on adjunctive
      dexamethasone therapy in adults with bacterial meningitis suffered from
      methodological flaws. In 2002, a trial with sufficient study-power to show
      significant differences was published. This study showed that adjunctive
      dexamethasone therapy reduced the rate of unfavorable outcomes from 25 to 15% in
      adults with bacterial meningitis. In this study, adjunctive treatment with
      dexamethasone was given before or with the first dose of antibiotics, without
      serious adverse effects. A quantitative review showed a consistent beneficial
      effect of dexamethasone on mortality and a borderline statistical beneficial
      effect on neurologic sequels. On the basis of available evidence, adjunctive
      dexamethasone therapy should be initiated before or with the first dose of
      antibiotics and continued for four days in all adults with suspected or proven
      community bacterial meningitis in high-income countries, regardless of bacterial
      etiology. Since prompt use of dexamethasone and appropriate antibiotics improves
      the prognosis of adults with bacterial meningitis, hospitals will need protocols
      to include dexamethasone with the initial antibiotic therapy.

PMID- 19386457
TI  - True pancreaticoduodenal artery aneurysms: a decision analysis.
AB  - PURPOSE: True pancreaticoduodenal artery aneurysms are rare. No definitive study
      evaluating the natural history of these lesions or their preferred method of
      treatment has been published. The purpose of this study was to evaluate the
      outcome of preventive treatment of unruptured pancreaticoduodenal artery
      aneurysms using a Markov model. MATERIALS AND METHODS: With the use of a Markov
      model, we performed a decision analysis to evaluate the outcome of preventive
      treatment of unruptured pancreaticoduodenal artery aneurysms. The risk of rupture
      and the mortality of preventive treatment are unknown. Therefore, we performed
      sensitivity analysis using these parameters. Effectiveness was measured in life
      expectancy. RESULTS: For 80-year-old patients, preventive treatment was dominated
      by no treatment if mortality rates of preventive treatment were greater than
      1.4%, greater than 2.6%, greater than 3.8%, and greater than 4.8% at annual
      rupture rates of 1%, 2%, 3%, and 4%, respectively. For 50-year-old patients,
      preventive treatment was dominated by no treatment if mortality rates of
      preventive treatment were greater than 3.3%, greater than 5.9%, greater than
      8.0%, and greater than 9.7% at annual rupture rates of 1%, 2%, 3%, and 4%,
      respectively. CONCLUSION: The effectiveness of preventive treatment of unruptured
      pancreaticoduodenal artery aneurysms depends on the aneurysm rupture rate,
      mortality rate of preventive treatment, and patient age. Taking into account the
      effects of these parameters is important in making treatment decisions.

PMID- 19386458
TI  - Initiation of the adventure of X-rays in Turkey.
AB  - Following the discovery of X-rays by Wilhelm Conrad ROENTGEN in 1895, the
      interest in these rays increased in many countries, and studies were initiated
      for the use of this discovery in the field of medicine. The contributions of Dr.
      Esad Feyzi, and Dr. Rifat Osman who later joined him, are significant with
      respect to introducing the knowledge about ROENTGEN rays to Turkey in a very
      short time span. In this article, we will briefly mention the initiation period
      of the adventure of X-rays in Turkey. All medical fields should be aware of their
      own histories. Only in this way the future of sciences may be shaped through a
      healthier progress.

PMID- 19386459
TI  - Study of the destructive effect to inherent quality of Angelicae dahuricae radix
      (Baizhi) by sulfur-fumigated process using chromatographic fingerprinting
      analysis.
AB  - The after-harvesting sun-dried process of Angelicae dahuricae radix (Chinese
      name: Baizhi) was previously the traditional treatment for commodity. Over recent
      decades the natural drying process for some fleshy roots or rhizomes of Chinese
      materia medica has been replaced by sulfur-fumigation for curtailing the drying
      duration and pest control. We used high performance liquid chromatography (HPLC)
      and high performance thin-layer chromatography (HPTLC) fingerprinting analysis to
      investigate the potential damaging effect of the sulfur-fumigating process. The
      experimental conditions were as follows. HPTLC analysis was carried out on pre
      coated silica-gel 60 plate, twice development was performed with two solvent
      systems (mobile phase) A, chloroform-ethyl acetate (10:1) and B, hexane
      chloroform-ether (4:1:2); the fluorescent images were observed under UV 365 nm.
      HPLC was preceeded on Zorbax SB-C(18) column; the linear gradient elution was
      conducted with mobile phase prepared from methanol-0.5% acetic acid; column
      temperature was at 25 degrees C; the detection wavelength was 250 nm. We found
      serious degradation of the majority of coumarins in sulfur-fumigated Baizhi. The
      destructive effect was manifested by the defaced chromatographic profile and
      verified by imitating the sulfur dioxide reaction with the constituents in Baizhi
      in the laboratory. It is suggested that sulfur-fumigation process is an
      unacceptable approach for processing herbal drugs.

PMID- 19386460
TI  - "It's not like I can change my mind later": reversibility and decision timing in
      prostate cancer treatment decision-making.
AB  - OBJECTIVE: To explore whether reversibility, decision timing, and uncertainty are
      relevant to men deciding on treatment for localized prostate cancer (LPC).
      DESIGN: Secondary qualitative data analysis of unstructured interviews. METHODS:
      Content analysis of previously collected qualitative data (31 individual
      interviews, 5 focus groups). We identified the frequency of references to
      reversibility, decision timing, and uncertainty and related sub-themes. RESULTS:
      We identified eight themes: reversibility, timing of decision, number of options,
      "getting it over with," "the way I make decisions," uncertainty among experts,
      desire for certainty, and probability. Fifteen men mentioned reversibility in
      individual interviews; 13 mentioned the importance of the timing of their
      decision. Eleven mentioned the importance of the number of options; twelve "the
      way I make decisions." Eleven men mentioned the uncertainty of experts, fourteen
      the desire to "get it over with," and six a desire for certainty. CONCLUSION:
      This study provides compelling preliminary data suggesting that men consider the
      reversibility, decision timing, and uncertainty in the prostate cancer treatment
      decision. PRACTICE IMPLICATION: These findings may be helpful in enhancing
      support for men facing the treatment decision.

PMID- 19386461
TI  - Health literacy and self-efficacy for participating in colorectal cancer
      screening: The role of information processing.
AB  - OBJECTIVE: This study aimed to document the association between health literacy
      and willingness and ability to seek information about the new colorectal cancer
      (CRC) screening program in the UK.(1) We also assessed self-efficacy for
      screening to determine the impact of health literacy on perceived confidence to
      take part in screening. METHODS: Ninety-six participants aged 50-69 years
      completed the British version of the Test of Functional Health Literacy in Adults
      (TOFHLA) (UK-TOFHLA) and used an interactive information menu to select
      information on why and how to participate in CRC screening. We derived a measure
      of reading effort by calculating the average amount of time spent reading
      individual information links. Each participant also completed a measure of
      comprehension, and self-efficacy for participating in screening. RESULTS: A
      multivariate analysis supported the hypothesis that lower health literacy would
      be associated with less information-seeking (b=.079, 95% confidence interval,
      .001-.157) greater effort in reading (b=-.965, 95% CI, -1.457 to -.473) and less
      self-efficacy for CRC screening (b=.61, 95% CI, .009-.131). CONCLUSION: Lower
      health literacy had a direct impact on information-seeking. It was also
      independently associated with perceived confidence to participate in screening.
      PRACTICE IMPLICATIONS: Reliance on printed communication when inviting low
      literate adults for screening can be problematic. The independent association
      between health literacy and self-efficacy further adds to the challenge of
      developing accessible and effective health promotion materials in this area.

PMID- 19386462
TI  - Bilingual health literacy assessment using the Talking Touchscreen/la Pantalla
      Parlanchina: Development and pilot testing.
AB  - OBJECTIVE: Current health literacy measures are too long, imprecise, or have
      questionable equivalence of English and Spanish versions. The purpose of this
      paper is to describe the development and pilot testing of a new bilingual
      computer-based health literacy assessment tool. METHODS: We analyzed literacy
      data from three large studies. Using a working definition of health literacy, we
      developed new prose, document and quantitative items in English and Spanish.
      Items were pilot tested on 97 English- and 134 Spanish-speaking participants to
      assess item difficulty. RESULTS: Items covered topics relevant to primary care
      patients and providers. English- and Spanish-speaking participants understood the
      tasks involved in answering each type of question. The English Talking
      Touchscreen was easy to use and the English and Spanish items provided good
      coverage of the difficulty continuum. CONCLUSION: Qualitative and quantitative
      results provided useful information on computer acceptability and initial item
      difficulty. After the items have been administered on the Talking Touchscreen (la
      Pantalla Parlanchina) to 600 English-speaking (and 600 Spanish-speaking) primary
      care patients, we will develop a computer adaptive test. PRACTICE IMPLICATIONS:
      This health literacy tool will enable clinicians and researchers to more
      precisely determine the level at which low health literacy adversely affects
      health and healthcare utilization.

PMID- 19386463
TI  - [New biological and radiological markers in amyotrophic lateral sclerosis].
AB  - The only specific marker of sporadic amyotrophic lateral sclerosis (ALS), that
      represent about 90% of all cases, is neuropathological and based on the
      demonstration of motoneuronal degeneration associated with typical inclusions
      positive for ubiquitine and TDP-43. The gene encoding the superoxide dismutase 1
      (SOD1) is implicated in about 10-20% of familial ALS. A mutation in the SOD1 gene
      can be considered as a genetic marker of ALS, and not a polymorphism, if the
      mutation has been shown to be pathogenic or to segregate to the disease in
      familial cases. Studies in blood or cerebral spinal fluid have shown biological
      changes involving different physiopathological pathways (oxidative stress,
      inflammation, excitotoxicity...). These abnormalities are neither sensitive nor
      specific enough to provide a diagnostic tool. The ectopic expression of Nogo-A in
      muscle biopsy is a promising marker but further studies are needed to demonstrate
      its value as a diagnostic tool in ALS. Studies in series of ALS patients have
      shown that MR-spectroscopy and diffusion tensor imaging can detect cortico-spinal
      degeneration. However, because of an overlap between patients and normal
      subjects, spectroscopic and DTI-parameters cannot be used as diagnostic tool in
      individual patients. In the future, a combination of biological, radiological and
      electrophysiological markers, rather than a single marker, may provide diagnostic
      tool for the diagnosis and follow-up of ALS patients.

PMID- 19386464
TI  - [Deep cerebral venous system thrombosis: a CT sign not to be missed].

PMID- 19386465
TI  - [Angiogenesis and thyroid cancer].
AB  - During the last two decades, the understanding of molecular biology of thyroid
      cancers has greatly improved, and this has permitted the development of novel
      therapeutic tools in patients with refractory disease. Kinase inhibitors inhibit
      kinases of the vascular endothelial growth factor (VEGF) receptors, and by doing
      this inhibit angiogenesis, and some of these agents also inhibit other kinases of
      the MAPkinase pathway. These inhibitors are effective in differentiated and
      medullary thyroid cancers, and induce a partial response or a long term
      stabilisation in more than half of patients.

PMID- 19386466
TI  - [Medullary compression by Burkitt lymphoma in an adult].

PMID- 19386467
TI  - Hopfield neural networks for on-line parameter estimation.
AB  - This paper addresses the problem of using Hopfield Neural Networks (HNNs) for on
      line parameter estimation. As presented here, a HNN is a nonautonomous nonlinear
      dynamical system able to produce a time-evolving estimate of the actual
      parameterization. The stability analysis of the HNN is carried out under more
      general assumptions than those previously considered in the literature, yielding
      a weaker sufficient condition under which the estimation error asymptotically
      converges to zero. Furthermore, a robustness analysis is made, showing that,
      under the presence of perturbations, the estimation error converges to a bounded
      neighbourhood of zero, whose size decreases with the size of the perturbations.
      The results obtained are illustrated by means of two case studies, where the HNN
      is compared with two other methods.

PMID- 19386468
TI  - Intelligence in the brain: a theory of how it works and how to build it.
AB  - This paper presents a theory of how general-purpose learning-based intelligence
      is achieved in the mammal brain, and how we can replicate it. It reviews four
      generations of ever more powerful general-purpose learning designs in Adaptive,
      Approximate Dynamic Programming (ADP), which includes reinforcement learning as a
      special case. It reviews empirical results which fit the theory, and suggests
      important new directions for research, within the scope of NSF's recent
      initiative on Cognitive Optimization and Prediction. The appendices suggest
      possible connections to the realms of human subjective experience, comparative
      cognitive neuroscience, and new challenges in electric power. The major challenge
      before us today in mathematical neural networks is to replicate the "mouse
      level", but the paper does contain a few thoughts about building, understanding
      and nourishing levels of general intelligence beyond the mouse.

PMID- 19386469
TI  - Adaptive learning via selectionism and Bayesianism, Part I: connection between
      the two.
AB  - According to the selection-by-consequence characterization of operant learning,
      individual animals/species increase or decrease their future probability of
      action choices based on the consequence (i.e., reward or punishment) of the
      currently selected action (the so-called "Law of Effect"). Under Bayesianism, on
      the other hand, evidence is evaluated based on likelihood functions so that
      action probability is modified from a priori to a posteriori according to the
      Bayes formula. Viewed as hypothesis testing, a selectionist framework attributes
      evidence exclusively to the selected, focal hypothesis, whereas a Bayesian
      framework distributes across all hypotheses the support from a piece of evidence.
      Here, an intimate connection between the two theoretical frameworks is revealed.
      Specifically, it is proven that when individuals modify their action choices
      based on the selectionist's Law of Effect, the learning population, on the
      ensemble level, evolves according to a Bayesian-like dynamics. The learning
      equation of the linear operator model [Bush, R. R., & Mosteller, F. (1955).
      Stochastic models for learning, New York: John Wiley and Sons], under ensemble
      averaging, yields the class of predictive reinforcement learning models (e.g.,
      [Busemeyer, J. R., & Myung, I. J. (1992). An adaptive approach to human decision
      making: Learning theory, decision theory, and human performance. Journal of
      Experimental Psychology: General, 121, 177-194; Montague, P. R., Dayan, P., &
      Sejnowski, T. J. (1996). A framework for mesencephalic dopamine systems based on
      predictive Hebbian learning. Journal of Neuroscience, 16, 1936-1947]).

PMID- 19386470
TI  - Complex and chaotic dynamics in a discrete-time-delayed Hopfield neural network
      with ring architecture.
AB  - This paper is devoted to the analysis of a discrete-time-delayed Hopfield-type
      neural network of p neurons with ring architecture. The stability domain of the
      null solution is found, the values of the characteristic parameter for which
      bifurcations occur at the origin are identified and the existence of Fold/Cusp,
      Neimark-Sacker and Flip bifurcations is proved. These bifurcations are analyzed
      by applying the center manifold theorem and the normal form theory. It is proved
      that resonant 1:3 and 1:4 bifurcations may also be present. It is shown that the
      dynamics in a neighborhood of the null solution become more and more complex as
      the characteristic parameter grows in magnitude and passes through the
      bifurcation values. A theoretical proof is given for the occurrence of Marotto's
      chaotic behavior, if the magnitudes of the interconnection coefficients are large
      enough and at least one of the activation functions has two simple real roots.

PMID- 19386471
TI  - Intraosseous lipoma of the mandible: a case report and review of the literature.
AB  - Intraosseous lipoma is a benign tumor of the bone. It is mostly seen in the
      metaphyses of the long bones and calcaneus. There are few documented cases of
      intraosseous lipomas in the jaw. Clinically, the lesion is usually silent and
      radiologically it appears as a radiolucent area rarely including some radio
      opacities. Diagnosis is based on clinical, radiological and histopathological
      features. Surgical removal of the lesion is the recommended treatment. The
      authors report a rare case of an intraosseous mandibular lipoma in a 45-year-old
      female, and review previously documented cases in the English literature. The
      histopathological and radiological features of the lesion are emphasized.

PMID- 19386472
TI  - Why all the confusion? Experimental task explains discrepant semantic priming
      effects in schizophrenia under "automatic" conditions: evidence from Event
      Related Potentials.
AB  - The schizophrenia research literature contains many differing accounts of
      semantic memory function in schizophrenia as assessed through the semantic
      priming paradigm. Most recently, Event-Related Potentials (ERPs) have been used
      to demonstrate both increased and decreased semantic priming at a neural level in
      schizophrenia patients, relative to healthy controls. The present study used ERPs
      to investigate the role of behavioral task in determining neural semantic priming
      effects in schizophrenia. The same schizophrenia patients and healthy controls
      completed two experiments in which word stimuli were identical, and the time
      between the onset of prime and target remained constant at 350 ms: in the first,
      participants monitored for words within a particular semantic category that
      appeared only in filler items (implicit task); in the second, participants
      explicitly rated the relatedness of word-pairs (explicit task). In the explicit
      task, schizophrenia patients showed reduced direct and indirect semantic priming
      in comparison with healthy controls. In contrast, in the implicit task,
      schizophrenia patients showed normal or, in positively thought-disordered
      patients, increased direct and indirect N400 priming effects compared with
      healthy controls. These data confirm that, although schizophrenia patients with
      positive thought disorder may show an abnormally increased automatic spreading
      activation, the introduction of semantic decision-making can result in abnormally
      reduced semantic priming in schizophrenia, even when other experimental
      conditions bias toward automatic processing.

PMID- 19386474
TI  - Antimicrobial activity against Helicobacter pylori strains and antioxidant
      properties of blackberry leaves (Rubus ulmifolius) and isolated compounds.
AB  - Rubus spp. (Rosaceae) provide extracts used in traditional medicine as
      antimicrobial, anticonvulsant, muscle relaxant and radical scavenging agents.
      Resistance to antibiotics used to treat Helicobacter pylori infection as well as
      their poor availability in developing countries prompted us to test the
      antimicrobial activity of Rubus ulmifolius leaves and isolated polyphenols
      against two H. pylori strains with different virulence (CagA+ strain 10K and
      CagA(-) strain G21). The antioxidant activity (TEAC values) of the tested
      compounds ranged from 4.88 (gallic acid) to 1.60 (kaempferol), whilst the leaf
      extract gave a value of 0.12. All the isolated polyphenols as well as the leaf
      extract showed antibacterial activity against both of the H. pylori strains. The
      minimum bactericidal concentrations (MBCs) of the extract for H. pylori strains
      G21 and 10K, respectively, were 1200 microg/mL and 1500 microg/mL after 24h of
      exposure and 134 microg/mL and 270 microg/mL after 48 h exposure. Ellagic acid
      showed very low MBC values towards both of the H. pylori strains after 48 h (2
      microg/mL and 10 microg/mL for strains G21 and 10K, respectively) and kaempferol
      toward G21 strain (MBC=6 microg/mL). A relationship between antimicrobial
      activity and antioxidant capacity was found only for H. pylori strain G21 CagA(-)
      strain.

PMID- 19386473
TI  - An upregulation of DNA-methyltransferase 1 and 3a expressed in telencephalic
      GABAergic neurons of schizophrenia patients is also detected in peripheral blood
      lymphocytes.
AB  - Several lines of schizophrenia (SZ) research suggest that a functional
      downregulation of the prefrontal cortex GABAergic neuronal system is mediated by
      a promoter hypermethylation, presumably catalyzed by an increase in DNA
      methyltransferase-1 (DNMT-1) expression. This promoter hypermethylation may be
      mediated not only by DNMT-1 but also by an entire family of de novo DNA
      methyltransferases, such as DNA-methyltransferase-3a (DNMT-3a) and -3b (DNMT-3b).
      To verify the existence of an overexpression of DNMT-3a and DNMT-3b in the brain
      of schizophrenia patients (SZP), we compared their mRNA expression in Brodmann's
      area 10 (BA10) and in the caudate nucleus and putamen obtained from the Harvard
      Brain Tissue Resource Center (Belmont, MA) from both nonpsychiatric subjects
      (NPS) and SZP. Our results demonstrate that DNMT-3a and DNMT-1 are expressed and
      co-localize in distinct GABAergic neuron populations whereas DNMT-3b mRNA is
      virtually undetectable. We also found that unlike DNMT-1, which is frequently
      overexpressed in telencephalic GABAergic neurons of SZP, DNMT-3a mRNA is
      overexpressed only in layer I and II GABAergic interneurons of BA10. To ascertain
      whether these DNMT expression differences observed in brain tissue could also be
      detected in peripheral tissues, we studied whether DNMT-1 and DNMT-3a mRNAs were
      overexpressed in peripheral blood lymphocytes (PBL) of SZP. Both DNMT-1 and DNMT
      3a mRNAs are expressed in the PBL and although DNMT-3a mRNA levels in the PBL are
      approximately 1/10 of those of DNMT-1, the comparison of the PBL content in NPS
      and SZP showed a highly significant 2-fold increase of both DNMT-1 and DNMT-3a
      mRNA in SZP. These changes were unaffected by the dose, the duration, or the type
      of antipsychotic treatment. The upregulation of DNMT-1 and to a lesser extent
      that of DNMT-3a mRNA in PBL of SZP supports the concept that this readily
      available peripheral cell type can express an epigenetic variation of specific
      biomarkers relevant to SZ morbidity. Hence, PBL studies may become useful to
      investigate a diagnostic epigenetic marker of SZ morbidity.

PMID- 19386475
TI  - Effect of perospirone on P300 electrophysiological activity and social cognition
      in schizophrenia: a three-dimensional analysis with sloreta.
AB  - The purpose of this study was to determine if perospirone, a second generation
      antipsychotic drug and partial agonist at serotonin-5-HT(1A) receptors, enhances
      electrophysiological activity, such as event-related potentials (ERPs), in
      frontal brain regions, as well as cognitive function in subjects with
      schizophrenia. P300 current source images were obtained by means of standardized
      low resolution brain electromagnetic tomography (sLORETA) before and after
      treatment with perospirone for 6 months. Perospirone significantly increased P300
      current source density in the left superior frontal gyrus, and improved positive
      symptoms and performance on the script tasks, a measure of verbal social
      cognition, while verbal learning memory tended to be improved. There was a
      significant correlation between the changes in P300 amplitude on the left frontal
      lead and those in social cognition. These results suggest the changes in three
      dimensional distribution of cortical activity, as demonstrated by sLORETA, may
      mediate some of the actions of antipsychotic drugs. The distinct cognition
      enhancing profile of perospirone in patients with schizophrenia may be related to
      its actions on 5-HT(1A) receptors.

PMID- 19386476
TI  - Increased choline-containing compounds in the orbitofrontal cortex and
      hippocampus in euthymic patients with bipolar disorder: a proton magnetic
      resonance spectroscopy study.
AB  - The neuronal mechanisms underlying the pathophysiology of bipolar disorder (BD)
      have not been fully characterized. The aim of this study was to compare
      metabolite levels in the hippocampus and the orbitofrontal cortex in a homogenous
      population of 12 euthymic patients with well-established BD and 12 age- and sex
      matched healthy comparison subjects. Using a GE Signa, 3-Tesla scanner, we
      performed proton magnetic resonance spectroscopy (H-MRS) to examine levels of N
      acetyl aspartate, glutamate and choline-containing compounds. Choline-containing
      compounds were significantly increased in the hippocampus and the orbitofrontal
      cortex in BD patients relative to control subjects. Significant elevations of
      glycerophosphocholine+phosphocholine (GPC+PCh) were measured in the hippocampus
      and the orbitofrontal cortex of patients. As choline is a marker of membrane
      phospholipid metabolism, the elevated choline in patients may indicate increased
      membrane breakdown in the brain regions examined. Abnormal neuronal loss within
      the hippocampus and orbitofrontal cortex further supports previous work
      suggesting that these regions are involved in the pathophysiology of BD.

PMID- 19386478
TI  - Maximum tolerated dose and early response - results of a phase I trial of
      paclitaxel and cisplatin with radiation therapy in carcinoma of the cervix.
AB  - AIMS: Cisplatin-based chemotherapy with radiotherapy is currently the standard
      treatment for locally advanced carcinoma of the cervix. Recent studies have shown
      a better response with the addition of newer chemotherapeutic agents. The aim of
      this phase I study was to establish the maximum tolerated dose (MTD) of
      paclitaxel in combination with cisplatin as a radiosensitiser along with
      radiation therapy in the treatment of carcinoma of the cervix and to analyse the
      toxicity profile of the combination regimen. MATERIALS AND METHODS: In total, 21
      newly diagnosed patients with squamous cell carcinoma of the cervix,
      International Federation of Gynecology and Obstetrics stage IB to IIIB were
      included in this trial. All patients received external beam radiation therapy to
      the pelvis (50 Gy in 25 fractions) delivered by conventional four-field box
      technique followed by low dose rate brachytherapy. Concurrent chemotherapy was
      administered with weekly cisplatin (30 mg/m(2)) and an escalating dose of weekly
      paclitaxel starting at 10 mg/m(2) up to 50 mg/m(2) (according to the modified
      Fibonacci series). RESULTS: The MTD of weekly paclitaxel was found to be 40
      mg/m(2). The dose-limiting toxicity that occurred in our patients at a dose of 50
      mg/m(2) weekly paclitaxel was grade 3 proctitis and vaginitis. CONCLUSION: In
      this phase I trial of concurrent radiation and combination chemotherapy with
      weekly paclitaxel and cisplatin (30 mg/m(2)/week), the MTD of paclitaxel was
      found to be 40 mg/m(2). This combination was feasible, with an acceptable
      toxicity profile.

PMID- 19386477
TI  - Beyond NMR spectra of antimicrobial peptides: dynamical images at atomic
      resolution and functional insights.
AB  - There is a considerable current interest in understanding the function of
      antimicrobial peptides for the development of potent novel antibiotic compounds
      with a very high selectivity. Since their interaction with the cell membrane is
      the major driving force for their function, solid-state NMR spectroscopy is the
      unique method of choice to study these insoluble, non-crystalline, membrane
      peptide complexes. Here I discuss solid-state NMR studies of antimicrobial
      peptides that have reported high-resolution structure, dynamics, orientation, and
      oligomeric states of antimicrobial peptides in a membrane environment, and also
      address important questions about the mechanism of action at atomic-level
      resolution. Increasing number of solid-state NMR applications to antimicrobial
      peptides are expected in the near future, as these compounds are promising
      candidates to overcome ever-increasing antibiotic resistance problem and are well
      suited for the development and applications of solid-state NMR techniques.

PMID- 19386479
TI  - Even-toed but uneven in length: the digits of artiodactyls.
AB  - In captive ruminants housed in small enclosures, hypertrophy of the outer hooves
      of the hindlimbs is often observed. We hypothesised that the underlying cause is
      overload attributable to an asymmetry of the digits, especially with respect to
      their length. To test this hypothesis, the bones of the digits of four species of
      artiodactyls, which included 11 wild chamois (Rupicapra rupicapra), 11 captive
      fallow deer (Dama dama), 11 captive bison (Bison bison) and 11 European moose
      (Alces alces; 9 wild, 2 captive), were radiographed post mortem and measured
      using a computer programme. In addition, the dimensions of the outer and inner
      hooves were measured directly with a caliper. The mean lengths of the epiphysis
      of the fourth metacarpal/metatarsal bone and the first and second phalanges of
      the fourth digit were greater than that of the third digit, whereas the third
      phalanx of the third digit had a greater mean length. The mean total length of
      the fourth digit of the forelimbs was greater than that of the third digit in 73
      95% of specimens, depending on species. In the hindlimbs, the fourth digit was
      longer in 91-100% of the specimens. The hooves of the fourth digit were
      significantly broader than the hooves of the third digit, whereas the inner
      hooves of the third digits had a greater toe length than those of the fourth
      digit. The paired digits of artiodactyls are uneven in length, which suggests a
      different function during stance and weight bearing. It is conceivable that this
      asymmetry is the result of selection processes that favoured locomotion on soft
      ground.

PMID- 19386480
TI  - Phyllanthus urinaria extract attenuates acetaminophen induced hepatotoxicity:
      involvement of cytochrome P450 CYP2E1.
AB  - Acetaminophen is a commonly used drug for the treatment of patients with common
      cold and influenza. However, an overdose of acetaminophen may be fatal. In this
      study we investigated whether mice, administered intraperitoneally with a lethal
      dose of acetaminophen, when followed by oral administration of Phyllanthus
      urinaria extract, may be prevented from death. Histopathological analysis of
      mouse liver sections showed that Phyllanthus urinaria extract may protect the
      hepatocytes from acetaminophen-induced necrosis. Therapeutic dose of Phyllanthus
      urinaria extract did not show any toxicological phenomenon on mice.
      Immunohistochemical staining with the cytochrome P450 CYP2E1 antibody revealed
      that Phyllanthus urinaria extract reduced the cytochrome P450 CYP2E1 protein
      level in mice pre-treated with a lethal dose of acetaminophen. Phyllanthus
      urinaria extract also inhibited the cytochrome P450 CYP2E1 enzymatic activity in
      vitro. Heavy metals, including arsenic, cadmium, mercury and lead, as well as
      herbicide residues were not found above their detection limits. High performance
      liquid chromatography identified corilagin and gallic acid as the major
      components of the Phyllanthus urinaria extract. We conclude that Phyllanthus
      urinaria extract is effective in attenuating the acetaminophen induced
      hepatotoxicity, and inhibition of cytochrome P450 CYP2E1 enzyme may be an
      important factor for its therapeutic mechanism.

PMID- 19386481
TI  - Modulating effect of Hesperidin on experimental murine colitis induced by dextran
      sulfate sodium.
AB  - Hesperidin, a flavanone-type flavonoid, is abundant in citrus fruit and has a
      wide range of pharmacological effects. Here we investigated the effect of
      Hesperidin on dextran sulphate sodium (DSS)-induced experimental ulcerative
      colitis in mice. Sulfasalazine (positive control) and Hesperidin in doses of 10,
      40 and 80 mg/kg were administered orally once a day for 7 days, beginning
      concurrently with exposure to DSS. The symptom of ulcerative colitis was
      evaluated by disease activity index (DAI) and the wet weight of colon.
      Myeloperoxidase (MPO) activity, malondialdehyde (MDA) content and the levels of
      interleukin-4 (IL-4) and interleukin-6 (IL-6) in serum were measured to observe
      the possible mechanisms. Oral administration of Hesperidin significantly
      decreased DAI, MPO activity, MDA content and the level of IL-6 in serum (p<0.01),
      while there was no significantly effect on the level of IL-4 in serum. These
      results demonstrate that Hesperidin can ameliorate DSS-induced experimental
      colitis, and may be useful in the prevention and treatment of colitis.

PMID- 19386482
TI  - Waste battery treatment options: comparing their environmental performance.
AB  - Waste consumer batteries are recycled using different routes based on
      hydrometallurgical and pyrometallurgical processes. Two hydrometallurgical and
      two pyrometallurgical treatment scenarios are compared starting from an average
      composition of Belgian waste batteries. The environmental performance is compared
      using life cycle analysis (LCA). The recycling rate is studied through mass
      balance calculation. Each treatment scenario results in a specific recycling
      rate. The environmental impact and benefits also vary between the treatment
      options. There is no such thing as a typical hydrometallurgical or
      pyrometallurgical treatment. When applying a hydrometallurgical treatment
      scenario, the focus lies on zinc and iron recycling. When allowing manganese
      recycling, the energy demand of the hydrometallurgical process increases
      considerably. Both pyrometallurgical options recycle zinc, iron and manganese.
      According to the LCA, none of the treatment scenarios performs generally better
      or worse than the others. Each option has specific advantages and disadvantages.
      The Batteries Directive 2006/66/EC sets out a recycling rate of 50% for consumer
      waste batteries. Based on metal recycling alone, the mass balances show that the
      target is difficult to obtain.

PMID- 19386483
TI  - Vision and the establishment of direction-selectivity: a tale of two circuits.
AB  - Direction-selective neurons, which respond selectively to motion in one
      direction, have been characterized in visual circuits across many species.
      Recently, the development of these directional neurons has been explored in both
      retina and primary visual cortex (V1). The development of direction-selective
      cells in V1 requires visual experience. In contrast, direction-selective ganglion
      cells in retina are present at the age of the earliest light responses. The
      vision-independent signals guiding the asymmetric wiring underlying retinal
      direction selectivity remain unknown. The details of how retinal and cortical
      circuits extract motion information could explain their differing requirements
      for visual experience in development.

PMID- 19386484
TI  - Evolution of protein modularity.
AB  - Proteins in their evolution appear to follow several discrete stages, which is
      reflected in their modular organization. The sequences of the protein modules are
      highly variable while their functions and structures are rather conserved. The
      relatedness of the variable sequences is well represented by the networks in
      natural protein sequence space that also suggests evolutionary connections.

PMID- 19386485
TI  - Pathogens and antibiotic residues in animal manures and hygienic and ecological
      risks related to subsequent land application.
AB  - The practice of spreading of livestock wastes onto land used for the production
      of food or animal feeds is widely regarded as the least environmentally damaging
      disposal method, however, the practice is still fraught with pitfalls such as N
      pollution of air and water and significant microbiological risks. Therefore this
      paper focuses on some of the latest developments that provide new insights into
      the microbiological safety of animal manures, the related treatment options and
      the spreading the products onto land. In conclusion the paper stresses the need
      to fully address issues concerning environmental contamination and transmission
      of antimicrobial-resistant bacteria through livestock manure, improve current
      environmental regulations regarding manure management practice and coordination
      of research activities and dissemination of technical information.

PMID- 19386486
TI  - Comparison of several methods for effective lipid extraction from microalgae.
AB  - Various methods, including autoclaving, bead-beating, microwaves, sonication, and
      a 10% NaCl solution, were tested to identify the most effective cell disruption
      method. The total lipids from Botryococcus sp., Chlorella vulgaris, and
      Scenedesmus sp. were extracted using a mixture of chloroform and methanol (1:1).
      The lipid contents from the three species were 5.4-11.9, 7.9-8.1, 10.0-28.6, 6.1
      8.8, and 6.8-10.9 g L(-1) when using autoclaving, bead-beating, microwaves,
      sonication, and a 10% NaCl solution, respectively. Botryococcus sp. showed the
      highest oleic acid productivity at 5.7 mg L(-1)d(-1) when the cells were
      disrupted using the microwave oven method. Thus, among the tested methods, the
      microwave oven method was identified as the most simple, easy, and effective for
      lipid extraction from microalgae.

PMID- 19386487
TI  - Effect of immobilization of a bacterial consortium on diuron dissipation and
      community dynamics.
AB  - This work intended to study the relationship between diuron herbicide dissipation
      and the population dynamics of co-cultivated Delftia acidovorans WDL34 (WDL34)
      and Arthrobacter sp. N4 (N4) for different cell formulations: free cells or
      immobilization in Ca-alginate beads of one or both strains. GFP-tagged WDL34 and
      N4 Gram staining allowed analyzing the cell growth and distribution of each
      strain in both beads and culture medium in the course of the time. Compared to
      the free cell co-culture of WDL34 and N4, immobilization of WDL34 in Ca-alginate
      beads co-cultivated with free N4 increased the dissipation rate of diuron by 53%
      (0.141 mg ml(-1) h(-1)). In that case, immobilization strongly modified the final
      equilibrium among both strains (highest total N4 to WDL34 ratio). Our results
      demonstrated that the inoculant formulation played a major role in the cell
      growth of each cultivated strain possibly increasing diuron dissipation. This
      optimized cell formulation may allow improving water and soil treatment.

PMID- 19386488
TI  - Effects of biomass weight and light intensity on the performance of
      photosynthetic microbial fuel cells with Spirulina platensis.
AB  - Microalgae Spirulina platensis were attached to the anode of a membrane-free and
      mediator-free microbial fuel cell (MFC) to produce electricity through the
      consumption of biochemical compounds inside the microalgae. An increase in open
      circuit voltage (OCV) was observed with decreasing light intensity and optimal
      biomass area density. The highest OCV observation for the MFC was 0.39 V in the
      dark with a biomass area density on the anode surface of 1.2 g cm(-2).
      Additionally, it was observed that the MFC with 0.75 g cm(-2) of biomass area
      density produced 1.64 mW m(-2) of electrical power in the dark, which is superior
      to the 0.132 mW m(-2) produced in the light. Which also means the MFC can be
      applied to generate electrical power under both day and night conditions.

PMID- 19386489
TI  - Selective recovery of precious metals by persimmon waste chemically modified with
      dimethylamine.
AB  - Persimmon waste was chemically modified with dimethylamine (DMA) to obtain a
      tertiary-amine-type gel, named DMA persimmon waste gel (DMA-PW). It was found to
      be effective for the adsorption of Au(III), Pd(II), and Pt(IV) in hydrochloric
      acid medium. In contrast, base metals such as Cu(II), Zn(II), Fe(III), and Ni(II)
      were not practically adsorbed. The formation of ion pairs of the metal chloro
      complex anions with the protonated adsorption gels was proposed as the main
      adsorption process. The gel exhibited selectivity only for precious metals with a
      remarkably high capacity for Au(III), i.e., 5.63 mol/kg dry gel and comparable
      capacities, i.e., 0.42 and 0.28 mol/kg for Pd(II) and Pt(IV), respectively.
      According to the kinetic and electrochemical studies, the adsorption rate of
      Au(III) was greatly enhanced by the chemical modification. Also, its excellent
      adsorption characteristics for the precious metals were confirmed by adsorption
      and elution tests using a column packed with the DMA-PW gel.

PMID- 19386490
TI  - Identified biosynthetic pathway of aspergiolide A and a novel strategy to
      increase its production in a marine-derived fungus Aspergillus glaucus by feeding
      of biosynthetic precursors and inhibitors simultaneously.
AB  - Aspergiolide A is a novel anti-tumor anthraquinone derivant produced by marine
      derived fungus Aspergillus glaucus. To identify its biosynthetic pathway and
      further improve the production, the effects of biosynthetic pathway specific
      inhibitors and precursors were investigated. Cerulenin and iodoacetamide, the
      specific inhibitors of polyketide pathway, could completely inhibit the
      aspergiolide A accumulation. Putative precursors of polyketide pathway could
      increase aspergiolide A production greatly, such as 6 mM acetate increased
      production by 135%. Simvastatin and citrate, the inhibitors of mevalonate
      pathway, stimulated the production by 63% and 179%, respectively. Considering
      that acetyl-CoA is the common starter unit in both polyketide and mevalonate
      pathway, a novel strategy was designed to stimulate the aspergiolide A
      accumulation. Combinations of 12 mM acetate with 0.3 mM simvastatin could
      increase the production by 151%, while the supplementation with 12 mM acetate and
      12 mM citrate brought a 262% increase of aspergiolide A production. The strategy
      might be very useful to enhance the production of other secondary metabolites
      derived from polyketide pathway.

PMID- 19386491
TI  - Studies on Guizotia abyssinica L. oil: biodiesel synthesis and process
      optimization.
AB  - Guizotia abyssinica seeds, a common bird feedstock, have been explored for the
      potential of biodiesel synthesis. The oil was extracted from the seeds by solvent
      extraction and composition of G. abyssinica oil was examined. The reaction
      parameters for biodiesel synthesis have been optimized. Temperature, oil:
      methanol ratio, catalyst type and catalyst concentration were found to have
      significant role on ester conversion. According to this study, the maximum yield
      of ester (98.7%) can be obtained with optimized sodium methoxide catalyst dosage
      (0.6%) at an operational temperature of 65 degrees C. Methyl ester of G.
      abyssinica oil was also studied for its oxidation stability and low temperature
      properties. Further, the synthesized product was blended in diesel at 5-20%
      ratios and evaluated for physico-chemical properties.

PMID- 19386492
TI  - Effect of xylanase supplementation of cellulase on digestion of corn stover
      solids prepared by leading pretreatment technologies.
AB  - Solids resulting from pretreatment of corn stover by ammonia fiber expansion
      (AFEX), ammonia recycled percolation (ARP), controlled pH, dilute acid, lime, and
      sulfur dioxide (SO(2)) technologies were hydrolyzed by enzyme cocktails based on
      cellulase supplemented with beta-glucosidase at an activity ratio of 1:2,
      respectively, and augmented with up to 11.0 g xylanase protein/g cellulase
      protein for combined cellulase and beta-glucosidase mass loadings of 14.5 and
      29.0 mg protein (about 7.5 and 15 FPU, respectively)/g of original potential
      glucose. It was found that glucose release increased nearly linearly with
      residual xylose removal by enzymes for all pretreatments despite substantial
      differences in their relative yields. The ratio of the fraction of glucan removed
      by enzymes to that for xylose was defined as leverage and correlated
      statistically at two combined cellulase and beta-glucosidase mass loadings with
      pretreatment type. However, no direct relationship was found between leverage and
      solid features following different pretreatments such as residual xylan or acetyl
      content. However, acetyl content not only affected how xylanase impacted
      cellulase action but also enhanced accessibility of cellulose and/or cellulase
      effectiveness, as determined by hydrolysis with purified CBHI (Cel7A).
      Statistical modeling showed that cellulose crystallinity, among the main
      substrate features, played a vital role in cellulase-xylanase interactions, and a
      mechanism is suggested to explain the incremental increase in glucose release
      with xylanase supplementation.

PMID- 19386493
TI  - Surfactant modified barley straw for removal of acid and reactive dyes from
      aqueous solution.
AB  - A barley straw was modified by a surfactant, cetylpyridinium chloride, and used
      as an adsorbent for acid (acid blue 40) and reactive dye (reactive black 5)
      adsorption in aqueous solution. Characterization of the modified barley straw was
      performed using N(2) adsorption, titration, and FT-IR analysis. It was found that
      the surfactant modified barley straw exhibits higher adsorption to acid blue 40
      than reactive black 5 and adsorption of the dyes is influenced by several
      parameters such as dye initial concentration, adsorbent dosage, solution pH, and
      adsorption temperature. Adsorption isotherms show that maximum adsorption of acid
      blue 40 and reactive black 5 is 1.02x10(-4) and 2.54x10(-5) mol/g, respectively.
      Desorption studies show that both dyes are strongly bounded with the adsorbent
      and exhibit low desorption.

PMID- 19386494
TI  - Heavy metal fractionation during the co-composting of biosolids, deinking paper
      fibre and green waste.
AB  - Due to the introduction of the European Union Landfill Directive, composting has
      become a potentially viable disposal route for some organic wastes. As waste
      derived compost is frequently added to soil to improve soil quality, it is
      important to quantify the environmental risk posed by potentially toxic elements
      contained within it. Here we used a sequential chemical extraction procedure to
      investigate the temporal dynamics of heavy metals (Cu, Zn, Pb and Ni) during the
      co-composting of biosolids, deinking paper fibre and green waste. Overall,
      composting over 26 weeks reduced the availability of Ni, had no effect on Pb and
      slightly increased the availability of Cu and Zn. We conclude that although the
      total Cu and Ni concentrations in the compost exceed legislative guidelines for
      land application, due to their recalcitrant nature within the compost, this
      compost posed very little threat to soil or plant quality if used in agriculture
      or land restoration.

PMID- 19386495
TI  - Efficient synthesis of Idraparinux, the anticoagulant pentasaccharide.
AB  - An efficient [DEF+GH] route was developed to the synthesis of Idraparinux, which
      is a fully O-sulfated, O-methylated mimic of the unique Antithrombin III binding
      domain of heparin.

PMID- 19386496
TI  - Synthesis of analogs of forodesine HCl, a human purine nucleoside phosphorylase
      inhibitor-Part II.
AB  - Forodesine HCl is being investigated as a potential therapeutic target for the
      control of T-cell proliferation. During the filing process for a New Drug
      Application (NDA) it became evident that there was a need to synthesize some
      stereo-isomers of forodesine HCl. Herein we present the synthesis of these three
      novel compounds (2-4).

PMID- 19386497
TI  - Benzothiophene piperazine and piperidine urea inhibitors of fatty acid amide
      hydrolase (FAAH).
AB  - The synthesis and structure-activity relationships (SAR) of a series of
      benzothiophene piperazine and piperidine urea FAAH inhibitors is described. These
      compounds inhibit FAAH by covalently modifying the enzyme's active site serine
      nucleophile. Activity-based protein profiling (ABPP) revealed that these urea
      inhibitors were completely selective for FAAH relative to other mammalian serine
      hydrolases. Several compounds showed in vivo activity in a rat complete Freund's
      adjuvant (CFA) model of inflammatory pain.

PMID- 19386498
TI  - Synthesis of analogs of forodesine HCl, a human purine nucleoside phosphorylase
      inhibitor-Part I.
AB  - Forodesine HCl is being investigated as a potential therapeutic target for the
      control of T-cell proliferation. During our ongoing process development work on
      forodesine HCl several novel compounds were identified as possible impurities in
      the process. Herein we present the synthesis of three novel compounds (2-4).

PMID- 19386499
TI  - Novel immunoconjugates comprised of streptonigrin and 17-amino-geldanamycin
      attached via a dipeptide-p-aminobenzyl-amine linker system.
AB  - Cytotoxic agents streptonigrin and 17-amino-geldanamycin were linked to
      monoclonal antibodies (mAbs), forming antibody-drug conjugates (ADCs) for antigen
      mediated targeting to cancer cells. The drugs were conjugated with a linker
      construct that is labile to lysosomal proteases and incorporates a valine-alanine
      p-aminobenzyl (PAB)-amino linkage for direct attachment to the electron-deficient
      amine functional groups present in both drugs. The resulting ADCs release drug
      following internalization into antigen-positive cancer cells. The drug linkers
      were conjugated to mAbs cAC10 (anti-CD30) and h1F6 (anti-CD70) via alkylation of
      reduced interchain disulfides to give ADCs loaded with 4 drugs/mAb. The
      streptonigrin ADCs were potent and immunologically specific on a panel of cancer
      cell lines in vitro and in a Hodgkin lymphoma xenograft model. We conclude that
      streptonigrin ADCs are candidates for further research, and that the novel linker
      system used to make them is well-suited for the conjugation of cytotoxic agents
      containing electron-deficient amine functional groups.

PMID- 19386500
TI  - Brown-Sequard syndrome associated with Horner's syndrome following a penetrating
      drill bit injury to the cervical spine.
AB  - We report a 41-year-old male who presented with a partial Brown-Sequard syndrome
      and Horner's syndrome following a penetrating drill bit injury to his mid
      cervical spine. As the injury was not a complete hemisection of the spinal cord,
      the patient presented with ipsilateral motor deficit and hyperesthesia and
      diminished contralateral fine touch sensation; however, proprioception, vibration
      and temperature were all initially intact. A cervical CT and MRI scan showed a
      damaged spinal cord at the C5/6 level with posterior cord compression secondary
      to haematoma. A decompressive laminectomy and evacuation of the haematoma was
      performed. Over the following 5 days the patient's right-sided motor deficit
      improved daily; however, he developed a contralateral deficit to pain and
      temperature upon wakening from the operation which did not resolve. The right
      sided Horner's syndrome also persisted.

PMID- 19386501
TI  - Discovery, synthesis, and biological evaluation of piperidinol analogs with anti
      tuberculosis activity.
AB  - Direct anti-tuberculosis screening of commercially available compound libraries
      identified a novel piperidinol with interesting anti-tuberculosis activity and
      drug like characteristics. To generate a structure activity relationship about
      this hit a 22 member optimization library was generated using parallel synthesis.
      Products of this library 1-((R)-3-(4-chlorophenoxy)-2-hydroxypropyl)-4-(4-chloro
      3-(trifluoromethyl) phenyl)piperidin-4-ol and 1-((S)-3-(4-(trifluoromethyl)
      phenoxy)-2-hydroxypropyl)-4-(4-chloro-3-(trifluoromethyl) phenyl) piperidin-4-ol
      demonstrated good anti-tuberculosis activity. Unfortunately, side effects were
      observed upon in vivo anti-tuberculosis testing of these compounds precluding
      their further advancement, which may be in part due to the secondary pharmacology
      associated with the aryl piperidinol core.

PMID- 19386502
TI  - 3D QSAR of novel estrogen-RGD peptide conjugates: getting insight into structural
      dependence of anti-osteoporosis activity and side effect of estrogen in ERT.
AB  - To explore the structural dependence of the oral potency and side effect of
      estrogen-RGD peptide conjugates, here six novel conjugates were prepared via
      introducing RGD-tetrapeptides into both 3- and 17-positions of estradiol, and
      introducing RGD-octapeptides into 3-position of estrone. In an ovariectomized
      mouse model they exhibited higher anti-osteoporosis activity and lower side
      effect than estrogen. For 3D QSAR analysis the anti-osteoporosis activities of
      nine known conjugates estrogen-RGD tetrapeptide conjugates were also provided.
      Using Cerius(2) module their 3D QSAR analysis was performed, four equations with
      high r(2) values were established, and the structural dependence of the oral
      potency and side effect of them was elucidated.

PMID- 19386503
TI  - Boron neutron capture therapy for an explanted organ: the logistical challenges.
AB  - Single liver metastases of colorectal cancer can be cured by surgery;
      disseminated liver metastases are incurable. A research group in Pavia, Italy,
      used BNCT as an experimental method to irradiate in curative intention the
      explanted liver of patients suffering from disseminated hepatic metastases. The
      situation in Pavia, where a reactor with a specially adapted thermal column and
      the hospital are close by, is unique. For the purpose of the present study, it
      was necessary to investigate how the Pavia experience can be repeated with
      transplantation centers located at distance from a reactor. Some basic
      investigations of the logistics of such a procedure are reported.

PMID- 19386504
TI  - Experimental feasibility studies on a SPECT tomograph for BNCT dosimetry.
AB  - This article reports on the development of a prototype of a SPECT tomograph
      system for online dosimetry in BNCT based on LaBr(3)(Ce) scintillation detectors.
      The setup shielding was optimized to be used in the accelerator based BNCT
      facility of the University of Birmingham. The system was designed and built. An
      image of a (241)Am point source was reconstructed. A projection of a phantom with
      two tumors with 400 microg/g of (10)B was measured at the BNCT facility.

PMID- 19386505
TI  - Tumor control and normal tissue complications in BNCT treatment of nodular
      melanoma: a search for predictive quantities.
AB  - A previous work concerning tumor control and skin damage in cutaneous melanoma
      treatments with BNCT has been extended to include doses, volumes and responses of
      104 subcutaneous lesions from all patients treated in Argentina. Acute skin
      reactions were also scored for these patients, and cumulative dose-area
      histograms and dose-based figures of merit for skin were calculated. Broadening
      the tumor response analysis with the latest data showed that the (minimum or
      mean) tumor dose is not a good predictor of the observed clinical outcome by
      itself. However, when the tumor volume was included in the model as second
      explicative variable, the dose increases its significance and becomes a critical
      variable jointly with the volume (p-values<0.05). A preliminary analysis to
      estimate control doses for two groups of tumor sizes revealed that for small
      tumor volumes (< 0.1cm(3)) doses greater than 20 Gy-Eq produce a high tumor
      control (> 80%). However, when tumor volumes are larger than 0.1cm(3), control is
      moderate (< 40%) even for minimum doses up to 40 Gy-Eq. Some quantities based on
      skin doses, areas and complication probabilities were proposed as candidates for
      predicting the severity of the early skin reactions. With the current data, all
      the evaluated figures of merit derived similar results: ulceration is present
      among the cases for which these quantities take the highest values.

PMID- 19386506
TI  - Accumulation of MRI contrast agents in malignant fibrous histiocytoma for
      gadolinium neutron capture therapy.
AB  - Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential,
      especially that gadolinium is generally used as a contrast medium in magnetic
      resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell
      line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI
      system. The commercially available MRI contrast medium Gd-DTPA (Magnevist,
      dimeglumine gadopentetate aqueous solution) and the biodegradable and highly
      gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were
      prepared as MRI contrast agents. The MFH cells were cultured and collected into
      three falcon tubes that were set into the 3-tesra MRI system to acquire signal
      intensities from each pellet by the spin echo method, and the longitudinal
      relaxation time (T1) was calculated. The amount of Gd in the sample was measured
      by inductively coupled plasma atomic emission spectrography (ICP-AES). The
      accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that
      in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd
      DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the
      larger accumulation exerted the adverse effect of lowering the enhancement of
      MRI. Further studies are warranted to gain insight into the therapeutic potential
      of Gd-NCT.

PMID- 19386507
TI  - Verification of the accuracy of BNCT treatment planning system THORplan.
AB  - THORplan is a treatment planning system developed at Tsing Hua University,
      Taiwan, for boron neutron capture therapy (BNCT) purpose. It is recently
      developed with user-friendly interface using Interactive Data Language. In this
      article the accuracy of THORplan is verified by comparing results of Snyder
      phantom calculation with the analytical model results of MCNP. Neutron source
      from THOR epithermal neutron beam is used as the source for the calculation. The
      thermal neutron flux calculated by THORplan is very close to the reference
      results. SERA overestimates thermal neutron flux by 2-5%. NCTPlan underestimates
      thermal neutron flux by 4-9% in most locations. The total weighted dose
      calculated by THORplan is accurate to within 3% except at the tissue interface.
      SERA overestimates the total weighted dose at depth >1.5 cm by 2-5%. NCTPlan
      underestimates the total weighted dose by approximately 10% at depth >1cm.

PMID- 19386508
TI  - A computational dosimetry tool for the study of tumor doses and skin toxicities
      in BNCT.
AB  - A Matlab-based computational tool, named SPHERE, was developed that helps
      determining tumor and skin doses in BNCT treatments. It was especially designed
      for cutaneous melanoma treatments and, among its features, it provides a guide
      for the location and delineation of tumors and a visual representation of
      superficial dose distributions (for both tumor and normal tissues). It also
      generates cumulative dose-volume histograms for different volumes of interest and
      dose-area histograms for skin. A description of the tool is presented, as well as
      examples of its application.

PMID- 19386509
TI  - Prompt gamma analysis of fly ash, silica fume and Superpozz blended cement
      concrete specimen.
AB  - Preventive measures against corrosion of reinforcing steel require making the
      concrete dense by adding pozzolanic materials, such as fly ash, silica fume,
      Superpozz, blast furnace slag, etc. to Portland cement. In order to obtain the
      desired strength and durability of concrete, it is desirable to monitor the
      concentration of the pozzolan in the blended cement concrete. Addition of
      pozzolan to blended cement changes the overall concentration of calcium and
      silicon in the blended cement concrete. The resulting variation in calcium and
      silicon gamma-ray yield ratio from blended cement concrete has found to have an
      inverse correlation with concentration of fly ash, silica fume, Superpozz, blast
      furnace slag in the blended cement concrete. For experimental verification of the
      correlation, intensities of calcium and silicon prompt gamma-ray due to capture
      of thermal neutrons in blended cement concrete samples containing 5-80% (by
      weight of cement) silica fume, fly ash and Superpozz were measured. The gamma-ray
      intensity ratio was measured from 6.42 MeV gamma-rays from calcium and 4.94 MeV
      gamma-ray from silicon. The experimentally measured values of calcium to silicon
      gamma-ray yield ratio in the fly ash, silica fume and Superpozz cement concrete
      specimens agree very well with the results of the Monte Carlo simulations.

PMID- 19386510
TI  - Caffeic acid modulates ultraviolet radiation-B induced oxidative damage in human
      blood lymphocytes.
AB  - Ultraviolet (UV) radiation causes inflammation, gene mutation and
      immunosuppressin in the human skin cells. These biological changes are
      responsible for photocarcinogenesis and photoaging. Normal lymphocytes are highly
      sensitive to the damaging effect of UV-radiation and undergo cell death. In the
      present study, the photoprotective effect of caffeic acid (3,4-dihydroxy cinnamic
      acid), a dietary phenolic compound, has been examined in the UVB (280-320)
      irradiated human blood lymphocytes. Lymphocytes pretreated with increasing
      concentration of caffeic acid (l, 5 and 10 microg/mL) for 30min were irradiated
      and lipid peroxidation, antioxidant defence status, cell viability (by MTT assay)
      and DNA damage (by comet assay) were examined. UVB-irradiation causes increased
      levels of lipid peroxidation, DNA damage and decreased antioxidant status, cell
      viability in human lymphocytes. Caffeic acid pretreatment significantly reduced
      the levels of lipid peroxidation markers i.e. thiobarbituric acid reactive
      substance (TBARS), lipid hydroperoxide (LPH), conjugated diene (CD) and decreased
      DNA damage (tail length and % tail DNA) in UVB-irradiated lymphocytes. Further,
      caffeic acid pretreatment significantly maintains antioxidant status and
      decreased UVB-induced cytotoxicity. The maximum dose of caffeic acid (l0
      microg/mL) normalized the UVB induced cellular changes indicating the
      photoprotective effect of caffeic acid in irradiated lymphocytes.

PMID- 19386511
TI  - Having a permanent resident in intensive care: the rewards and challenges.
AB  - BACKGROUND: Intensive care units are generally structured and staffed to care for
      short-term critically ill patients. This is in contrast to the increasing
      incidence of patients who require long-term (i.e. greater than 6 months)
      intensive care in the contemporary health care context. AIM: The aim of this
      paper is to share our experience of caring for a long-term ventilated patient in
      intensive care, including providing a summary of strategies and considerations
      that proved effective in our setting. PROCESS: Dealing with the initial reactions
      of the staff, patient and family was the first focus of care, with strategies
      developed to manage the psychological as well as practical challenges. Core to
      subsequent strategies was the early formation of a multi-disciplinary case
      management team. Ongoing challenges included integrating rehabilitation care into
      the intensive care, developing effective multi-dimensional communication
      strategies, facilitating appropriate involvement of the patient and her family,
      operationalising trips outside the intensive care environment and adapting the
      model of nursing care to suit the context. CONCLUSION: Elements essential for the
      effective care of a long-term patient within the intensive care setting included
      the development and maintenance of an open and honest relationship with the
      patient and family, regular multi-disciplinary case management meetings and
      effective communication strategies throughout the health care team. Importantly,
      clinical leaders should remain open to considering new ideas and strategies that
      facilitate effective care for a patient whose primary focus is different to the
      majority of intensive care patients.

PMID- 19386514
TI  - Fat containing HCC: findings on CT and MRI including serial contrast-enhanced
      imaging.
AB  - RATIONALE AND OBJECTIVES: The purpose of this article is to review the spectrum
      of computed tomography (CT) and magnetic resonance imaging (MRI) findings of fat
      containing hepatocellular carcinoma (HCC), including serial contrast-enhanced
      imaging. MATERIALS AND METHODS: Imaging findings of 10 fat-containing HCCs on CT
      (n = 2) or MRI (n = 3) or on both CT and MRI (n = 5) were retrospectively
      reviewed in 9 patients. Both techniques included serial contrast enhanced imaging
      in arterial, portal venous, and late venous phases. RESULTS: On non-contrast CT,
      fat containing HCC was either homogeneously hypodense (n = 6) or of mixed density
      (n = 1). The density values ranged between -11 and 9 HU. On MRI, homogenous (n =
      4) or heterogeneous (n = 4) signal loss was observed on T1-weighted out-of-phase
      images as compared to in-phase images. Enhancement patterns on serial contrast
      enhanced CT and MRI included: arterial enhancement indistinguishable from the
      liver with venous wash out (n = 2), arterial capillary blush with venous phase
      fading (n = 2), and heterogeneous arterial enhancement with unenhanced foci and
      venous phase wash out of enhancements. Larger lesions had late capsular
      enhancement. CONCLUSIONS: Fat containing HCC has spectrum of imaging findings on
      CT and MRI. MRI with chemical shift technique depicts the fat content. Arterial
      contrast enhancement with venous washout or fading may help for the diagnosis of
      HCC in inconclusive cases.

PMID- 19386513
TI  - Intestinal T cells: facing the mucosal immune dilemma with synergy and diversity.
AB  - The epithelium of the gastrointestinal tract, which represents the greatest body
      surface area exposed to the outside environment, is confronted with a plethora of
      foreign and potentially harmful antigens. Consequently, the immune system of the
      gut faces the daunting task of distinguishing harmless dietary proteins and
      commensal bacteria from potentially dangerous pathogens, and of then responding
      accordingly. Mucosal T cells play a central role in maintaining barrier function
      and controlling the delicate balance between immune activation and immune
      tolerance. This review will focus on the unique features of mucosal T cell
      subsets that reside in the epithelium and lamina propria of the gut.

PMID- 19386512
TI  - Barrier immunity and IL-17.
AB  - CD4+ T(H)17 cells display a featured role in barrier immunity. This effector
      population of T cells is important for clearance of microorganisms but can also
      promote autoimmunity at barrier sites. Recent work has indicated that these
      effector cells share a pathway with CD4+ regulatory T cells (T(R) cells) that
      also have a critical function in barrier protection and immune regulation. The
      development and function of T(H)17 cells, and their relationship with T(R) cells
      are discussed.

PMID- 19386515
TI  - Serum and stimulated whole saliva parathyroid hormone in menopausal women with
      oral dry feeling.
AB  - OBJECTIVE: The aim of this study was to evaluate the correlation of severity of
      oral dryness (OD) with serum and saliva parathyroid hormone (PTH) and calcium
      levels, and to compare serum and stimulated whole saliva PTH and calcium between
      menopausal women with/without OD. METHODS: A case-control study was carried out
      in 76 (38 as case and 38 as control) selected menopausal women with/without OD
      conducted at the Clinic of Oral Medicine, Tehran University of Medical Sciences
      (TUMS). Xerostomia Inventory (XI) score was also used as an index of OD severity.
      Serum and saliva Ca(+2) concentrations were assessed colorimetrically by Arsenazo
      reaction. PTH concentration was analyzed by enzyme-linked immunosorbent assay
      (ELISA). Statistical analysis of Student t test and Spearman correlation was
      used. RESULTS: The mean saliva calcium and PTH concentrations and outputs, and
      serum PTH were significantly higher in the case group, compared with control.
      However, there were no significant differences in serum calcium concentration and
      stimulated saliva flow rate between groups. XI score correlated significantly
      with serum PTH (r = 0.387, P = .004), saliva concentration (r = 0.382, P = .002)
      and output (r = 0.346, P = .007) of PTH; and also with saliva concentration (r =
      0.326, P = .013) and output (r = 0.315, P = .018) of calcium; but not with serum
      calcium and saliva flow rate. CONCLUSION: OD severity correlated positively with
      serum and stimulated whole saliva PTH, and with saliva calcium levels in this
      group of menopausal women. Thus, salivary calcium and PTH levels appear
      associated with OD and menopause.

PMID- 19386516
TI  - Advanced malignant minor salivary glands tumors of the oral cavity.
AB  - OBJECTIVE: Intraoral minor salivary gland carcinomas (MSGC) are rare tumors with
      different frequency, distribution, and prognostic factors relating to overall
      survival. STUDY DESIGN: From 1992 to 2006, a total of 95 patients with MSGC
      originating in the oral cavity were analyzed by univariate and multivariate
      analysis using the log-rank test and Cox-regression. RESULTS: Fifty-four percent
      of all patients had a low-grade disease and 46% had a high grade disease. The 2-,
      5-, and 10-year overall survivals were 82%, 73%, and 58%, respectively. The T (P
      = .007), N category (P = .010), UICC stage (P = .021), and resection margin
      status (P < .0001) statistically influenced survival, whereas the M status did
      not (P = .16). Salvage treatment influenced the patients' overall survival
      significantly (P < .0001). CONCLUSION: This study confirms that in MSGC salvage
      surgery and tumor stage correlates well with prognosis. More studies are
      necessary to confirm prognostic factors and determine the true frequency of MSGC
      in the oral cavity.

PMID- 19386517
TI  - Bone mass and trabecular pattern in the mandible as an indicator of skeletal
      osteopenia: a 10-year follow-up study.
AB  - OBJECTIVES: The aim of this investigation was to evaluate mandibular trabecular
      pattern as an indicator of osteopenia and bone mineral density (BMD) changes in
      relation to mandibular bone changes. STUDY DESIGN: Forty females (49 to 80 years
      old) underwent intraoral radiography and BMD examinations 10 years apart. The
      trabecular pattern was assessed visually (Lindh's index), bone texture digitally,
      and bone mass by its grey-level values. RESULTS: With the exception of one
      subject, all individuals with sparse trabeculation were found to be osteopenic.
      All mandibular variables were tested for correlations with forearm and hip BMDs.
      They predicted forearm BMD, but adjusted for body mass index not hip BMD. Age,
      body mass index, and mandibular variables explained 29% to 64% of BMD variance.
      BMD changes correlated with body mass index change, bone texture change, and
      trabeculation change. CONCLUSIONS: Mandibular variables identify individuals with
      low BMD, but they are not discriminating enough for osteoporosis diagnostics.
      Mandibular bone changes correlated with forearm BMD changes.

PMID- 19386518
TI  - Three-dimensional analysis of maxillary first molar mesiobuccal root canal
      configuration and curvature using micro-computed tomography.
AB  - OBJECTIVE: The complex anatomic configuration of the maxillary first molar
      mesiobuccal (MB) root canal system has been the subject of several studies. The
      purpose of this investigation was to analyze the 3-dimensional (3D)
      characteristics of the maxillary first molar MB canal system using micro-computed
      tomography (microCT). STUDY DESIGN: Extracted maxillary first molars (46) were
      scanned by microCT and their canals reconstructed by 3D modeling software.
      RESULTS: In these MB roots, nearly two-thirds (65.2%) had 2 canals, fewer than
      one-third (28.3%) had only 1 canal, and a few (6.5%) had 3 canals. The most
      common root canal configuration was 2 distinct canals (type III: 37.0%), followed
      by 1 single canal (type I: 28.3%), 2 canals that joined together (type II:
      17.4%), 1 canal that split into 2 (type IV: 10.9%), and 3 canals (type V: 6.5%).
      CONCLUSION: MicroCT provided an in-depth analysis of canal configurations, as
      well as length, curvature, and location of calcified segments.

PMID- 19386519
TI  - Comparative investigation of 2 rotary nickel-titanium instruments: protaper
      universal versus protaper.
AB  - OBJECTIVE: The objective of this study was to evaluate whether the changes in the
      design of the ProTaper canal instruments contribute to the shaping ability of the
      instrument in terms of the morphology of curved canals measured by the cross
      sectional area using the Bramante method. STUDY DESIGN: Ten extracted human
      mandibular molars with root canal curvatures between 25 degrees and 41 degrees
      were used. Ten mesiobuccal canals were instrumented with ProTaper and 10
      mesiolingual canals were instrumented with ProTaper Universal rotary instruments.
      Pre- and postoperative sections were obtained from the coronal, middle, and
      apical portions and analyzed. Statistical analysis was performed using the
      Student t test (P < .05). RESULTS: No statistically significant difference was
      observed in terms of amount of dentin removed, transportation, variation of canal
      shape factor or change in working length, and working time (P > .05). Only one
      instrument fracture (F2 in the ProTaper group) and 2 instrument deformations (S1
      and F3 in ProTaper and ProTaper Universal, respectively) were noted. CONCLUSION:
      Within the limitations of this study, the modifications on ProTaper instruments
      were found to not create any discrepancy on the shaping abilities of instruments
      and the evaluated other factors. In addition, both rotary nickel-titanium
      instruments prepared a well-shaped root canal with minimal canal transportation.

PMID- 19386520
TI  - Condyle replacement after tumor resection: comparison of individual prefabricated
      titanium implants and costochondral grafts.
AB  - OBJECTIVE: The indications for temporomandibular joint (TMJ) reconstruction are
      well established, but the method of reconstruction is controversial. The purpose
      of this retrospective study was to compare individual prefabricated condyle
      implants and costochondral grafts in condyle reconstruction after tumor
      resection. STUDY DESIGN: We conducted a retrospective review of a case series
      with 28 patients treated with costochondral grafting and 23 patients treated with
      individual prefabricated titanium implants. For each patient, variables included
      both subjective (pain and interference with eating) and objective (interincisal
      distance) data. RESULTS: Baseline patient characteristics were similar in the 2
      groups; all patients were followed for a minimum of 2 years. Patients in both
      groups showed an improvement in symptoms. Those treated with individual
      prefabricated implants had greater improvement and fewer complications than those
      in the costochondral group; also, more patients in the autogenous group required
      reoperation. CONCLUSION: Individual prefabricated condyle implants are effective
      in reconstruction of TMJ tumor defects. These prostheses are a viable choice in
      the setting of tumor resection and reconstruction, with improvement of jaw
      function, reduction of joint pain, and esthetic improvement.

PMID- 19386521
TI  - Assessment of linear and angular measurements on three-dimensional cone-beam
      computed tomographic images.
AB  - OBJECTIVE: The purpose of this research was to provide further evidence to
      demonstrate the precision and accuracy of maxillofacial linear and angular
      measurements obtained by cone-beam computed tomography (CBCT) images. STUDY
      DESIGN: The study population consisted of 15 dry human skulls that were submitted
      to CBCT, and 3-dimensional (3D) images were generated. Linear and angular
      measurements based on conventional craniometric anatomical landmarks, and were
      identified in 3D-CBCT images by 2 radiologists twice each independently.
      Subsequently, physical measurements were made by a third examiner using a digital
      caliper and a digital goniometer. RESULTS: The results demonstrated no
      statistically significant difference between inter- and intra-examiner analysis.
      Regarding accuracy test, no statistically significant differences were found of
      the comparison between the physical and CBCT-based linear and angular
      measurements for both examiners (P = .968 and .915, P = .844 and .700,
      respectively). CONCLUSIONS: 3D-CBCT images can be used to obtain dimensionally
      accurate linear and angular measurements from bony maxillofacial structures and
      landmarks.

PMID- 19386522
TI  - Push-out bond strength and SEM evaluation of new polymeric root canal fillings.
AB  - OBJECTIVE: The objective of this study was to compare the interfacial strengths
      and failure modes of new polymeric endodontic obturation systems consisting of
      different material combinations. STUDY DESIGN: Extracted human single-rooted
      teeth (n = 105) were instrumented using HERO Shaper rotary instruments and
      obturated with different combinations of core and sealer as follows: group 1,
      RealSeal/Resilon; group 2, RealSeal/Herofill; group 3, Hybrid Root Seal/Resilon;
      group 4, Hybrid Root Seal/Herofill; group 5, MM-Seal/Resilon; group 6, MM
      Seal/Herofill; group 7 (control). Failure modes of root slices (1.00 +/- 0.05-mm
      thick) after push-out testing were examined with stereomicroscope and scanning
      electron microscopy. RESULTS: Hybrid Root Seal/Resilon combination had
      significantly greater bond strength than all the other groups (P < .001);
      RealSeal/Resilon combination proved to have the second highest bond strength (P <
      .001). Bond failure was mainly mixed failure in both adhesive and cohesive modes
      at the dentin/sealer interface. CONCLUSION: The push-out bond strengths of
      methacrylate-based sealers (Hybrid Root Seal and RealSeal) and thermoplastic
      synthetic-polymer-based core material (Resilon) combinations were higher than
      epoxy-resin-based sealer (MM-Seal) and gutta-percha (Herofill) combination.

PMID- 19386524
TI  - Veterinary medicine and animal behaviour: barking up the right tree!

PMID- 19386525
TI  - NMR with excitation modulated by Frank sequences.
AB  - Miniaturized NMR is of growing importance in bio-, chemical, and -material
      sciences. Other than the magnet, bulky components are the radio-frequency power
      amplifier and the power supply or battery pack. We show that constant flip-angle
      excitation with phase modulation following a particular type of polyphase perfect
      sequences results in low peak excitation power at high response peak power. It
      has ideal power distribution in both the time domain and the frequency domain. A
      savings in peak excitation power of six orders of magnitude has been realized
      compared to conventionally pulsed excitation. Among others, the excitation
      promises to be of use for button-cell operated miniature NMR devices as well as
      for complying with specific-absorption-rate regulations in high-field medical
      imaging.

PMID- 19386523
TI  - Post-translational modifications of Runx1 regulate its activity in the cell.
AB  - In this report we review the current knowledge of the interaction of RUNX1(AML1)
      with serine/threonine kinases, lysine and arginine methyltransferases, lysine
      acetyltransferases, and histone deacetylases. We also discuss the effect of RUNX1
      ETO fusion gene on DNA methylation. RUNX1 post-transcriptional modification can
      affect its role in influencing differentiation and self-renewal of hematopoietic
      cells. The goal of these studies is to develop targets for improved leukemia
      therapy.

PMID- 19386526
TI  - Predictive modeling of the total deactivation rate constant of singlet oxygen by
      heterocyclic compounds.
AB  - We constructed a predictive model of the total deactivation rate constant (k(t))
      of singlet oxygen by heterocyclic compounds that are widespread in biological
      systems and participate in highly relevant biologic functions related with
      photochemical processes, by means of quantitative structure-property
      relationships (QSPR). The study of the reactivity of singlet oxygen with
      biomolecules provides their antioxidant capability, and the determination of the
      rate constants allows evaluation of the efficiencies of these processes. Our
      optimal linear model based on 41 molecular structures, which have not been used
      previously in a QSPR study, consists of six variables, selected from more than
      thousand geometrical, topological, quantum-mechanical and electronic types of
      molecular descriptors. Our recently developed strategy to determine the optimal
      number of descriptors in model is successfully applied. As a practical
      application of our QSPR model we estimated the unknown k(t) of several
      heterocyclic compounds that are of particular interest for further experimental
      studies in our research group.

PMID- 19386527
TI  - Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results
      in serum protein profile changes in normal adult subjects.
AB  - OBJECTIVE: To identify biomarkers of growth hormone (GH) and insulin-like growth
      factor 1 (IGF-1) action in human serum. BACKGROUND: The search for new markers of
      GH activity has received extensive attention given that the current biomarkers
      (IGF-1, IGFBP-3 and collagen peptides) show substantial variability in the
      population, and are not reliably predictive of either the physiologic effects of
      GH therapy or the detection of GH abuse by athletes. GH releasing hormone (GHRH)
      is a polypeptide synthesized in the hypothalamus that binds to receptors on
      pituitary somatotropes to promote the synthesis and release of GH. Serum GH and
      IGF-1 levels have been shown to increase with administration of GHRH or CJC-1295,
      a long-acting GHRH analog. DESIGN: Sera from 11 healthy young adult men before
      and one week after CJC-1295 injection were analyzed by two-dimensional gel
      electrophoresis for proteomic changes. Serum proteins displaying significant
      changes before and after treatment were subsequently identified using mass
      spectrometry. In addition, correlations between these proteins and GH or IGF-1
      levels were evaluated. RESULTS: Two protein spots that displayed decreased
      intensities after treatment were identified as an apolipoprotein A1 isoform and a
      transthyretin isoform. Three protein spots upregulated by CJC-1295 treatment
      included beta-hemoglobin, a C-terminal fragment of albumin, and a mix of an
      immunoglobulin fragment and another C-terminal albumin fragment. A linear
      relationship was found between the spot containing immunoglobulin and albumin
      fragments and IGF-1 levels. CONCLUSIONS: Although the molecular mechanisms
      linking the identified proteins to GH and IGF-1 biological activity remain to be
      clarified, the results suggest that they represent potential biomarkers of GH
      and/or IGF-1 action.

PMID- 19386528
TI  - Influence of different Fletcher-Suit applicator geometries on sagittal dose
      distribution.
AB  - INTRODUCTION: One of the brachytherapy treatment modality of cervix carcinomas is
      insertion with Fletcher-Suit (FS) applicator. Depending on the patient anatomy
      and pathology and on the construction of the FS applicator different geometrical
      arrangements in ovoid separation, in ovoids' sagittal level with respect to the
      tandem were experienced. The multiple insertions show minor differences in
      applicator geometries. The aim of the study is to evaluate the influence of main
      geometrical parameters: the ovoid separation, symmetry and the ovoids' sagittal
      shift on dose distribution in different FS applicator arrangements. We tested the
      effect of dwell time settings in improvement of dose distribution of less
      adequate insertions. We also investigated the effect of inter-fractional
      variation of applicator geometry. MATERIALS AND METHODS: We considered 73
      treatment fractions of 22 patients. All insertions were performed by the same
      gynaecologist with the same type of FS applicator, while the treatment plans were
      generated by the same physicist using the same treatment planning method. We
      compared the sagittal dose distribution of different FS applicator geometries
      with dose levels at two applicator points, defined 2 cm apart from the tandem
      towards the bladder and rectum. We computed the Pearson correlation coefficients
      between the dose levels at the applicator points and the ovoid separation,
      symmetry and the ovoids' sagittal shift. We also investigated the effect of dwell
      time settings in ovoids in order to decrease the dose to organs at risk. The
      inter-fractional variation of the FS applicator geometries and the influence on
      the dose levels at the two applicator points were also tested. RESULTS AND
      CONCLUSIONS: Strong correlation was found between the ovoid separation and dose
      values to applicator points defined in sagittal direction of FS applicator
      arrangements. Also strong correlation was between the ovoids' sagittal position
      with respect to the tandem and the applicator point defined towards the rectum,
      while the ovoid symmetry had no influence on the sagittal dose distribution. The
      standard deviations of inter-fractional variation of the ovoid separation and the
      ovoids' sagittal position were within +/-5.2 mm and +/-10.2 mm respectively. The
      inter-fractional variations in FS applicator geometry resulted in variation in
      dose levels at the applicator points +/-0.8 Gy typically, while the largest value
      was +/-1.6 Gy.

PMID- 19386529
TI  - [The tympanic thermometer in pediatrics as an alternative to the mercury-in-glass
      thermometer].
AB  - OBJECTIVES: To determine the behavior of a new and smaller model of infrared
      thermometer cone and to assess whether it is an appropriate alternative to
      determine fever in children under 14-years-old. METHOD: We performed a cross
      sectional, descriptive study comparing the temperatures taken with a mercury
      thermometer with those taken by an infrared thermometer in children under 14
      years-old. The researchers followed the manufacturer's instructions for use for
      each thermometer. The overall sample of 400 children was divided into two age
      groups. Group I consisted of children aged less than 2 years and group II of 2-14
      years-old. In group I the rectal mercury thermometer was placed in the rectum for
      3 minutes and the tympanic thermometer was used in rectal mode and placed in the
      right ear. In group II, the axillary mercury thermometer was placed for 8 minutes
      in the right axilla and the tympanic thermometer was used in the axillary mode.
      To analyze intraobserver bias, 50 patients were selected from the sample and
      their temperatures were simultaneously taken by two nurses from the team. The
      intraclass correlation coefficient (ICC) was used both to measure the reliability
      of the tympanic thermometer and to analyze intraobserver bias. RESULTS:
      Temperature measurements with both instruments showed an ICC of 0.91 (95%
      confidence interval [CI], 0.88-0.94) for group I and 0.90 (95% CI, 0.87-0.92) for
      group II. The reproducibility of the measurements taken by the two nurses in 50
      patients showed an ICC of 0.97 (95% CI, 0.95-0.98) for the tympanic thermometer.
      CONCLUSIONS: The infrared thermometer is an appropriate device for rapidly
      measuring temperature in the emergency department. However, the measurements
      taken should be confirmed by another method when clinical decisions are based on
      temperature values.

PMID- 19386530
TI  - A fatal case of invasive fungal sinusitis by Scopulariopsis acremonium in a bone
      marrow transplant recipient.
AB  - A fatal case of Scopulariopsis acremonium sinus infection in an allogeneic
      hematopoietic stem cell transplant patient is reported. Rapid vascular diffusion
      of the fungus to the major head vessels was observed, which led to subsequent
      repeated cerebral ischemia and death. The presence of hyphae in the right carotid
      wall might be considered an indirect sign of fungal blood diffusion in the
      absence of positive blood cultures. The infection developed during the course of
      prolonged voriconazole prophylaxis, which was found to be effective in the in
      vitro antifungal drug assay. This finding induced us to consider the capacity of
      this drug to reach infected paranasal sinuses, and the need in cases such as this
      of a combined systemic and local pharmacological therapy or a combined medical
      and surgical approach.

PMID- 19386531
TI  - Ocular tuberculosis: diagnostic and treatment challenges.

PMID- 19386532
TI  - [Genotyping of blood group systems at the CNRGS. I: FY, JK, MNS systems].
AB  - AIM OF THE STUDY: Determination of blood group antigens from data obtained by
      using molecular methods (genotyping) has become an indispensable tool in the
      specialized immunohematology laboratories. The French National Reference Centre
      for Blood group typing (CNRGS) routinely performs genotyping of the FY, JK and
      MNS system (common genotyping), providing a phenotype deduced from genotyping
      data for FY1, FY2, JK1, JK2, MNS3 and MNS4 antigens. PATIENTS AND METHODS: We
      performed a study to evaluate the common genotyping prescriptions referred to the
      CNRGS over the last three years. RESULTS: Between February 2006 and February
      2009, the CNRGS performed 2392 genotyping, including 981 common genotyping.
      Analysis of 172 common genotyping performed in 2008 showed that 63.8% of the
      prescriptions expressed a genotyping demand. Of the latter, 42.7% were genotyping
      prescriptions only, whereas 57.2% were prescriptions of genotyping associated
      with alloantibody identification. All prescriptions refer to blood group
      genotyping indications issued from guidelines, with no incorrect prescription,
      that are patients transfused within four months before blood sampling in 63.6% of
      cases or a positive direct antiglobulin test in 24.5% of cases. Lastly, 36% of
      the blood samples referred to the CNRGS had no genotyping prescription. Yet,
      common genotyping was performed by the CNRGS to get complete immunohematology
      data for antibody identification. CONCLUSION: Usefulness of blood group
      genotyping in specialized immunohematology laboratories is obvious. However, the
      strategy for implementation of molecular methods remains to be defined. Use of
      high-throughput DNA analysis should change our way of working.

PMID- 19386533
TI  - Degradation of diclofenac during sonolysis, ozonation and their simultaneous
      application.
AB  - Diclofenac is a widely used anti-inflammatory non-steroidal drug that escapes
      conventional urban wastewater treatment trains because of its resistance to
      biodegradation. Therefore it is frequently found in treated effluents, lakes and
      rivers. It has been reported that diclofenac can exhibit adverse effects on
      aquatic organisms. Advanced oxidation processes like ozonation (O(3)) and
      sonolysis (US) can be employed for the removal of such recalcitrant compounds
      from water matrices. This study included the investigation of the efficiency of
      O(3) and US and also of their combined application (US+O(3)) for the degradation
      and potential mineralization of diclofenac in a water matrix. Under the
      conditions applied, all three systems proved to be effective in inducing
      diclofenac oxidation, leading to 22% of mineralization for O(3) and 36% for US
      after 40min of treatment. The synergy observed in the combined schemes, mainly
      due to the effects of US in enhancing the O(3) decomposition, led to higher
      mineralization (about 40%) for 40min treatment, and to a significantly higher
      mineralization level for shorter treatment duration.

PMID- 19386534
TI  - Auxin-regulated cell polarity: an inside job?
AB  - Auxin is now known to be a key regulator of polar events in plant cells. The
      mechanism by which auxin conveys a polar signal to the cell is unknown, but one
      well-known hypothesis is that the auxin flux across the plasma membrane regulates
      vesicle trafficking. This hypothesis remains controversial because of its
      reliance on an as-yet-undiscovered membrane flux sensor. In this article I
      suggest instead that the polar signal is the auxin gradient within the cell
      cytoplasm. A computer model of vascular development is presented that
      demonstrates the plausibility of this scenario. The auxin-binding protein ABP1
      might be the receptor for the auxin gradient.

PMID- 19386536
TI  - Determination by ultraviolet absorption spectrometry and theoretical calculation
      of dissociation constant of 1,2,3,9-tetrahydro-4H-carbazol-4-one.
AB  - The dissociation constant of 1,2,3,9-tetrahydro-4H-carbazol-4-one was determined
      by ultraviolet absorption spectrometry method based on the absorption spectra of
      1,2,3,9-tetrahydro-4H-carbazol-4-one at different pH in ethanol-water mixed
      solvents. The results show that the pK(b) was a good linear function of the
      volume fraction of ethanol in the concentration range studied. The dissociation
      constant of 1, 2, 3,9-tetrahydro-4H-carbazol-4-one in water were determined by
      extrapolation to be 14.04 under the condition of this experiment. The accurate
      pK(b) calculations of 1,2,3,9-tetrahydro-4H-carbazol-4-one have been investigated
      using the combination of the extended clusters-continuum model with the
      polarizable continuum solvation model (PCM). The calculations are performed at
      the B3LYP/6-31G levels. The formation of molecular clusters by means of the
      1,2,3,9-tetrahydro-4H-carbazol-4-one wrapped up with water molecules leads to the
      weakness of the interaction between the polar solvents and the 1,2,3,9-tetrahydro
      4H-carbazol-4-one, hence, the accuracy of pK(b) has been enhanced. The
      dissociation constant of 1,2,3,9-tetrahydro-4H-carbazol-4-one in water were
      calculated to be 14.10 and agreed well with experimental data.

PMID- 19386535
TI  - Seeing slow and seeing fast: two limits on perception.
AB  - Video cameras have a single temporal limit set by the frame rate. The human
      visual system has multiple temporal limits set by its various constituent
      mechanisms. These limits seem to form two groups. A fast group comprises
      specialized mechanisms for extracting perceptual qualities such as motion
      direction, depth and edges. The second group, with coarse temporal resolution,
      includes judgments of the pairing of color and motion, the joint identification
      of arbitrary spatially separated features, the recognition of words and high
      level motion. These temporally coarse percepts might all be mediated by high
      level processes. Working at very different timescales, the two groups of
      mechanisms collaborate to create our unified visual experience.

PMID- 19386537
TI  - Vibrational spectra of cysteine zwitterion and mechanism of its formation: bulk
      and specific solvent effects and geometry optimization in aqueous media.
AB  - Vibrational spectrum of the zwitterionic (Z)-forms of cysteine has been studied
      considering full geometry optimization under the bulk solvent effect of aqueous
      media combined with the solvent effect of up to three specific water molecules.
      The tautomerization barrier energy of the molecule from its normal (N) to the Z
      form has also been obtained. Geometry optimization was performed at the B3LYP/AUG
      cc-pVDZ level which was followed by single point energy calculations at the
      MP2/AUG-cc-pVDZ level of theory in both gas phase and aqueous media. Transition
      states (TS) were located between the N and Z-forms of cysteine complexed with one
      to three water molecules and also without any complexed water molecule. The bulk
      solvent effect of aqueous media was treated using the integral equation formalism
      of the polarizable continuum model (IEF-PCM). It has been found that the barrier
      energy decreases with the increasing number of complexed water molecules
      significantly. Two conformers (A, B) of Z-cysteine are found to have comparable
      stabilities. It is shown that agreement between the experimentally observed and
      our calculated vibrational frequencies for Z-cysteine, at the present level of
      treatment, is improved significantly for 22 out of 27 frequencies. For these 22
      frequencies, for the more stable conformer (A) of Z-cysteine, the rms value of
      differences between our calculated and experimentally observed frequencies
      reduces from 22 to 11 cm(-1) in going from 0 to 3 complexed water molecules.
      Certain vibrational frequencies have been identified with the help of which the
      conformers A and B of Z cysteine can be identified.

PMID- 19386538
TI  - Vibrational spectroscopic studies and DFT calculations of 4-aminoantipyrine.
AB  - The pyrazole derivative, 4-aminoantipyrine (4AAP), used as an intermediate for
      the synthesis of pharmaceuticals especially antipyretic and analgesic drugs has
      been analyzed experimentally and theoretically for its vibrational frequencies.
      The FTIR and FT Raman spectra of the title compound have been compared with the
      theoretically computed frequencies invoking the standard 6-311g(d,p) and cc-pVDZ
      basis sets at DFT level of theory (B3LYP). The harmonic vibrational frequencies
      at B3LYP/cc-pVDZ after appropriate scaling method seem to coincide satisfactorily
      with the experimental observations rather than B3LYP/6-311g(d,p) results. The
      theoretical spectrograms for FT-IR and FT-Raman spectra of 4AAP have been also
      constructed and compared with the experimental spectra. Additionally,
      thermodynamic data have also been calculated and discussed.

PMID- 19386539
TI  - Ternary complex formation of Eu(III) with o-phthalate in aqueous solutions.
AB  - Ternary hydroxo complex formation of Eu(III) with o-phthalate was investigated by
      potentiometry and fluorescence spectrophotometry. Curves of the equilibrium pH
      versus the amount of NaOH added showed that the pH value starting to form a
      Eu(III) precipitate was decreased due to the formation of a ternary hydroxo
      complex, EuOHL(s) (L = phthalate). The formation of EuOHL(s) was qualitatively
      confirmed by the enhancement of the fluorescence intensity of Eu(III) in the
      precipitate with the light absorbed by phthalate, and was quantitatively
      confirmed by the measurement of the amounts of Eu(III), OH(-) and phthalate
      included in the precipitate. The solubility product of EuOHL(s) was determined as
      pK(sp)(0) = 15.6+/-0.4. Characteristic features in the fluorescence spectra and
      the solubility product of the Eu(III)-phthalate complex were compared with those
      of the Eu(III)-PDA (PDA = pyridine-2,6-dicarboxylate) complex. The fluorescence
      intensity of the EuL(+) complex of L = PDA was about 11 times stronger than that
      of L = phthalate. The origin of the difference in the fluorescence intensity is
      discussed based on the intramolecular energy transfer effect from the lowest
      triplet energy level of the ligand to the resonance energy level of Eu(III).

PMID- 19386540
TI  - LinkEHR-Ed: a multi-reference model archetype editor based on formal semantics.
AB  - PURPOSE: To develop a powerful archetype editing framework capable of handling
      multiple reference models and oriented towards the semantic description and
      standardization of legacy data. METHODS: The main prerequisite for implementing
      tools providing enhanced support for archetypes is the clear specification of
      archetype semantics. We propose a formalization of the definition section of
      archetypes based on types over tree-structured data. It covers the specialization
      of archetypes, the relationship between reference models and archetypes and
      conformance of data instances to archetypes. RESULTS: LinkEHR-Ed, a visual
      archetype editor based on the former formalization with advanced processing
      capabilities that supports multiple reference models, the editing and semantic
      validation of archetypes, the specification of mappings to data sources, and the
      automatic generation of data transformation scripts, is developed. CONCLUSIONS:
      LinkEHR-Ed is a useful tool for building, processing and validating archetypes
      based on any reference model.

PMID- 19386541
TI  - Age and gender specific prevalence of HTLV-1.
AB  - BACKGROUND: The seroprevalence of Human T-cell Leukemia Virus Type 1 (HTLV-1) is
      female predominant despite the higher incidence of Adult T-cell Leukemia (ATL) in
      males. If the mother-to-child transmission of HTLV-1 is more common for male
      infants than in female infants, longer exposure to the virus for males may
      explain the paradoxically higher incidence of ATL. OBJECTIVES: To test the
      hypothesis that the seroprevalence of HTLV-1 is male predominant during
      adolescence. STUDY DESIGN: The presence of HTLV-1 antibody in 272,043 blood
      samples donated to a regional blood bank in an HTLV-1 high-endemic region was
      assessed. RESULTS: The entire population of female donors had a significantly
      higher seroprevalence compared to males (2.05% and 1.80%, respectively,
      p<0.0001). However, compared with male donors, the carrier rate for female donors
      was lower for the youngest subgroup (16-19 years, p=0.0011); was similar for the
      next two age subgroups (20-29 years and 30-39 years); and was significantly
      higher for the last two age subgroups (40-49 years and over 50-64 years, both
      p<0.0001). In general, older age subgroups led to higher seroprevalence in both
      genders. CONCLUSIONS: HTLV-1 infection is more common for males until after age
      20, when male to female sexual transmission becomes likely. This suggests that
      mother-to-child transmission is more common for males.

PMID- 19386542
TI  - Auditory discrimination profiles of speech sound changes in 6-year-old children
      as determined with the multi-feature MMN paradigm.
AB  - OBJECTIVE: A linguistic multi-feature mismatch negativity (MMN) paradigm with
      five types of changes (vowel, vowel-duration, consonant, frequency (F0), and
      intensity) in Finnish syllables was used to determine speech-sound discrimination
      in 17 normally-developing 6-year-old children. The MMNs for vowel and vowel
      duration were also recorded in an oddball condition in order to compare the two
      paradigms. Similar MMNs in the two paradigms would suggest that they tap the same
      processes. This would promote the usefulness of the more time-efficient multi
      feature paradigm for future studies in children. METHODS: MMNs to five deviant
      types were recorded in the multi-feature paradigm in which these deviants (total
      of 50%) were presented in an alternating fashion with standards (50%). An oddball
      condition with vowel and vowel-duration deviants served as a control. RESULTS:
      The linguistic multi-feature paradigm elicited significant MMN responses to all
      changes used and the responses were comparable to the ones recorded with the
      traditional oddball paradigm. Compared to a previous adult study (Pakarinen S,
      Lovio R, Huotilainen M, Alku P, Naatanen R, Kujala T. Fast multi-feature paradigm
      for recording several mismatch negativities (MMNs) to phonetic and acoustic
      changes in speech sounds. Biol Psychol, submitted for publication), the MMN
      amplitudes seemed to be smaller and of longer latencies in general in children
      than in adults. CONCLUSIONS: The new time-efficient paradigm can be used in
      studies addressing cortical speech-sound discrimination in young children.
      SIGNIFICANCE: The multi-feature paradigm enables fast (20 min) recording of MMNs
      for five speech-sound features. In future, it might be useful in detecting
      abnormalities in speech discrimination profiles of children with possible
      language-related disorders.

PMID- 19386543
TI  - Cholinergic modulation of MEG resting-state oscillatory activity in Parkinson's
      disease related dementia.
AB  - OBJECTIVE: EEG and MEG studies in Parkinson's disease (PD) related dementia (PDD)
      have shown a slowing of resting-state, oscillatory activity compared to non
      demented PD. Aim of the present MEG study was to determine whether treatment with
      the cholinesterase inhibitor rivastigmine would reverse this slowing of resting
      state activity in PDD patients. METHODS: In eight PDD patients, whole head MEG
      was recorded in a resting-state condition before and after treatment with
      rivastigmine. Relative spectral power was calculated in the delta, theta, alpha,
      beta and gamma frequency bands in fronto-central, parieto-occipital and temporal
      regions. RESULTS: After treatment with rivastigmine, PDD patients demonstrated an
      increase in relative power in the alpha range in parieto-occipital and temporal
      regions together with a diffuse increase in beta power. Furthermore, a decrease
      of delta power in fronto-central and parieto-occipital regions was found.
      CONCLUSIONS: Treatment with the cholinesterase inhibitor rivastigmine at least
      partly counteracts the slowing of resting-state brain activity that is known to
      occur in PD related dementia. SIGNIFICANCE: Our observations emphasize the
      prominent role of degeneration of the cholinergic system in the pathophysiology
      of dementia in PD. In the future, MEG might contribute to the selection of PD
      patients who may optimally benefit from cholinergic treatment.

PMID- 19386544
TI  - High plasticity in the production of diatom-derived polyunsaturated aldehydes
      under nutrient limitation: physiological and ecological implications.
AB  - Diatoms have evolved a silicified cell wall that provides an efficient barrier
      against herbivores. These microalgae also produce chemical compounds such as
      polyunsaturated aldehydes (PUAs) that can potentially impair recruitment and
      cause malformations in the offspring of such grazers. We measured silica content
      as an indication of cell wall thickness, organic nutrient cell quotas, PUAs and
      polyunsaturated fatty acid cell content in Skeletonema marinoi grown under N-, P-
      and Si-limitation in continuous cultures. A 7.5 fold increase in PUA production
      was observed (27.5 fmol cell(-1)) in Si-limited cells with respect to the
      controls, while Si content decreased by 50%. PUA production decreased in nitrogen
      limited cells to 0.14 fmol cell(-1) and increased 3 times in phosphorus-limited
      cells (7.53 fmol cell(-1)), while silica content increased by 20% in both cases.
      The substrate to product ratio suggested that production of the PUAs heptadienal
      and octadienal was limited by the amount of substrate under P- and Si-limitation,
      and by enzyme activity under N-limitation. Octatrienal production was likely
      limited by enzyme activity in all growth conditions. The high PUA levels produced
      under Si-limitation, when cells have a thinner cell wall, suggests a compensatory
      alternation of mechanical and chemical defense mechanisms.

PMID- 19386545
TI  - Phylogeny and taxonomy of Xanthophyceae (Stramenopiles, Chromalveolata).
AB  - The stramenopile class Xanthophyceae has been variously divided into two to seven
      orders. Previous molecular phylogenetic analyses of the class have had limited
      taxon/gene sampling or have focused on particular taxa. Despite these limitations
      para-polyphyletic groups have been identified at different taxonomic ranks. To
      investigate the phylogeny of the Xanthophyceae, a multiple alignment containing
      SSU rDNA, rbcL and psaA gene portions was analyzed according to bayesian
      inference, maximum likelihood, minimum evolution and maximum parsimony methods.
      This multigenic approach allowed robust resolution of evolutionary relationships
      within Xanthophyceae and the proposal of a taxonomic revision within the class.
      The best statistically supported tree either showed/or confirmed that several
      taxa at different taxonomic levels were para-polyphyletic. Ten epitypes were
      formally proposed for species of Chlorellidium, Botrydiopsis and Bumilleriopsis.
      Boundaries of these coccoid genera were redefined as monophyletic groups. Four
      major clades received strong statistical support. These accommodated most of the
      studied coccoid, filamentous and siphonous Xanthophyceae. Unicellular
      flagellates, amoeboid and palmelloid taxa were not included in the study.
      Botrydiopsis pyrenoidosa was excluded from Xanthophyceae and placed incertae
      sedis.

PMID- 19386546
TI  - Malignant fungating wounds: a survey of nurses' clinical practice in Switzerland.
AB  - BACKGROUND: The care of individuals with a fungating malignant wound represents
      challenging cancer management not only for patients and their families but also
      for health care professionals. Understanding the difficulties faced by nurses
      when they care for patients with such a wound can help guide practice and service
      development. The aim of this study was to investigate how many patients with a
      malignant fungating wounds did nurses see and what kind of difficulties in caring
      for patients with a malignant fungating wound did nurses experience. METHOD: A
      survey was conducted in three different geographical regions of Switzerland over
      a 6month period. RESULTS: A total of 269 nurses participated in this survey. The
      nurses reported the prevalence rate of fungating wounds as 6.6%. There was a
      difference in perceived prevalence between the regions. The most frequent
      location for such wounds was the breast in women with breast cancer. The
      appearance was mainly ulcerating. The main difficulties nurses experienced in the
      management of patients related to malodour, pain and difficulties in applying the
      dressings to the wound. The most frequently used dressing was an absorbent
      dressing. The difficulties nurses had and what kind of dressings they used were
      closely connected. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Strategies need to
      be explored to help understand the diverse range of wound problems including
      physical and psychological components. Furthermore, there is a need to raise the
      awareness of existing wound management specialists in the support of cancer
      patients.

PMID- 19386547
TI  - A comparison between infrared tympanic thermometry, oral and axilla with rectal
      thermometry in neutropenic adults.
AB  - BACKGROUND: This study assessed the agreement between infrared tympanic membrane
      (TM), axillary, corrected axillary (+0.5 degrees C), oral, and corrected oral
      (+0.3 degrees C) to rectal thermometry as reference standard in neutropenic
      adults. The sensitivity and specificity of the mentioned thermometries in
      detecting rectal fever (> or =38 degrees C) were also analysed. METHOD: This is a
      comparative diagnostic test study. A total of 400 sets of blinded simultaneous
      temperature readings were measured from 21 haemato-oncology in-patients with
      neutropenia following chemotherapy. Three-hundred sets were then randomly
      sampled. Agreements were analysed using random two-way intraclass correlation
      (ICC). Sensitivity and specificity were analysed using contingency 2x2 table.
      FINDINGS: Both right and left TM thermometry have good correlation with rectal
      thermometry; 0.810 (95% CI, 0.748-0.855) and 0.770 (95% CI, 0.713-0.815)
      respectively. Axilla thermometry has weak agreement (ICC 0.486 (95% CI, 0.118
      0.689)) with rectal thermometry. The sensitivity (sn) and specificity (sp) in
      detecting rectal fever (> or =38 degrees C) were: right TM (sn) 0.712 (95% CI,
      0.586-0.814), (sp) 0.957 (95% CI, 0.920-0.978); oral (sn) 0.561 (95% CI, 0.433
      0.681), (sp) 0.983 (95% CI, 0.954-0.995); and axilla (sn) 0.348 (95% CI, 0.238
      0.477), (sp) 0.996 (95% CI, 0.973-0.999). INTERPRETATION: Single tympanic
      membrane thermometry is in good agreement with rectal thermometry. It is more
      sensitive than oral or axillary thermometry in detecting rectal fever.

PMID- 19386550
TI  - Moments of movement: active learning and practice development.
AB  - As our understanding of practice development becomes more sophisticated, we
      enhance our understanding of how the facilitation of learning in and from
      practice, can be more effectively achieved. This paper outlines an approach for
      enabling and maximizing learning within practice development known as 'Active
      Learning'. It considers how, given establishing a learning culture is a
      prerequisite for the sustainability of PD within organisations, practice
      developers can do more to maximize learning for practitioners and other
      stakeholders. Active Learning requires that more attention be given by
      organisations committed to PD, at a corporate and strategic level for how
      learning strategies are developed in the workplace. Specifically, a move away
      from a heavy reliance on training may be required. Practice development
      facilitators also need to review: how they organise and offer learning, so that
      learning strategies are consistent with the vision, aims and processes of PD;
      have skills in the planning, delivery and evaluation of learning as part of their
      role and influence others who provide more traditional methods of training and
      education.

PMID- 19386549
TI  - Neuromuscular junction destruction during amyotrophic lateral sclerosis: insights
      from transgenic models.
AB  - Amyotrophic lateral sclerosis (ALS) represents the major adult-onset motor neuron
      disease. Analyses of ALS animal models have shown that motor neuron death starts
      with neuromuscular junction (NMJ) destruction and distal axonal degeneration.
      Most importantly, motor neuron death results from pathological events occurring
      outside the motor neuron, especially in glial cells and skeletal muscle and,
      surprisingly, is associated with pathological defects outside the motor system.
      In particular, ALS pathogenesis includes systemic defects such as muscle
      hypermetabolism, energy deficit, and widespread alterations of lipid metabolism
      that were shown to participate in motor neuron degeneration. Current research
      should now focus on understanding the relationships between these pathological
      hallmarks and how such global defects lead to the ALS-linked selective loss of
      motor neurons.

PMID- 19386551
TI  - Nurses' information retrieval skills in psychiatric hospitals - are the
      requirements for evidence-based practice fulfilled?
AB  - Nursing professionals have long recognized the importance to practice of research
      and the value of research evidence. Nurses still do not use research findings in
      practice. The purpose of this paper was to describe nurses' skills in using
      literature databases and the Internet in psychiatric hospitals and associations
      of nurses' gender, age, and job position with their information retrieval skills.
      The study was carried out in 2004 among nursing staff (N=183) on nine acute
      psychiatric wards in two psychiatric hospitals in Finland (n=180, response rate
      98%). The Finnish version of the European Computer Driving Licence test (ECDL)
      was used as a data collection instrument. The study showed that there were clear
      deficits in information retrieval skills among nurses working in psychiatric
      hospitals. Thus, nurses' competence does not support the realization of evidence
      based practice in the hospitals. Therefore, it is important to increase nurses'
      information retrieval skills by tailoring continuing education modules. It would
      be also advisable to develop centralized systems for the internal dissemination
      of research findings for the use of nursing staff.

PMID- 19386548
TI  - Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in
      patients with limited-stage small-cell lung cancer in complete remission after
      chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212,
      and IFCT 99-01): a randomised clinical trial.
AB  - BACKGROUND: The optimum dose of prophylactic cranial irradiation (PCI) for
      limited-stage small-cell lung cancer (SCLC) is unknown. A meta-analysis suggested
      that the incidence of brain metastases might be reduced with higher PCI doses.
      This randomised clinical trial compared the effect of standard versus higher PCI
      doses on the incidence of brain metastases. METHODS: Between September, 1999, and
      December, 2005, 720 patients with limited-stage SCLC in complete remission after
      chemotherapy and thoracic radiotherapy from 157 centres in 22 countries were
      randomly assigned to a standard (n=360, 25 Gy in 10 daily fractions of 2.5 Gy) or
      higher PCI total dose (n=360, 36 Gy) delivered using either conventional (18
      daily fractions of 2 Gy) or accelerated hyperfractionated (24 fractions in 16
      days with two daily sessions of 1.5 Gy separated by a minimum interval of 6 h)
      radiotherapy. All of the treatment schedules excluded weekends. Randomisation was
      stratified according to medical centre, age (</=60 and >60 years), and interval
      between the start of induction treatment and the date of randomisation (</=90, 91
      180, and >180 days). Eligible patients were randomised blindly by the data centre
      of the Institut Gustave Roussy (PCI99-01 and IFCT) using minimisation, and by the
      data centres of EORTC (EORTC ROG and LG) and RTOG (for CALGB, ECOG, RTOG, and
      SWOG), both using block stratification. The primary endpoint was the incidence of
      brain metastases at 2 years. Analysis was by intention-to-treat. This study is
      registered with ClinicalTrials.gov number NCT00005062. FINDINGS: Five patients in
      the standard-dose group and four in the higher-dose group did not receive PCI;
      nonetheless, all randomised patients were included in the effectiveness anlysis.
      After a median follow-up of 39 months (range 0-89 months), 145 patients had brain
      metastases; 82 in the standard-dose group and 63 in the higher-dose group. There
      was no significant difference in the 2-year incidence of brain metastases between
      the standard PCI dose group and the higher-dose group, at 29% (95% CI 24-35) and
      23% (18-29), respectively (hazard ratio [HR] 0.80 [95% CI 0.57-1.11], p=0.18).
      226 patients in the standard-dose group and 252 in the higher-dose group died; 2
      year overall survival was 42% (95% CI 37-48) in the standard-dose group and 37%
      (32-42) in the higher-dose group (HR 1.20 [1.00-1.44]; p=0.05). The lower overall
      survival in the higher-dose group is probably due to increased cancer-related
      mortality: 189 patients in the standard group versus 218 in the higher-dose group
      died of progressive disease. Five serious adverse events occurred in the standard
      dose group versus zero in the higher-dose group. The most common acute toxic
      events were fatigue (106 [30%] patients in the standard-dose group vs 121 [34%]
      in the higher-dose group), headache (85 [24%] vs 99 [28%]), and nausea or
      vomiting (80 [23%] vs 101 [28%]). INTERPRETATION: No significant reduction in the
      total incidence of brain metastases was observed after higher-dose PCI, but there
      was a significant increase in mortality. PCI at 25 Gy should remain the standard
      of care in limited-stage SCLC. FUNDING: Institut Gustave-Roussy, Association pour
      la Recherche sur le Cancer (2001), Programme Hospitalier de Recherche Clinique
      (2007). The European Organisation for Research and Treatment of Cancer (EORTC)
      contribution to this trial was supported by grants 5U10 CA11488-30 through 5U10
      CA011488-38 from the US National Cancer Institute.

PMID- 19386554
TI  - Sex differences in pain intensity in adolescents suffering from cancer:
      differences in pain memories?
AB  - Although sex differences have been investigated in chronic pain populations,
      little is known about sex differences in the pain experience of paediatric
      oncology patients and also whether their parents rate the pain experience
      differently for boys and girls. The aim of the present study was to determine if
      (1) boys and girls with cancer differ in current perception and past recollection
      of cancer-related pain and (2) if adolescents' and parents' pain ratings differ
      in relation to the sex of the adolescent. One hundred twelve adolescents with
      malignant diagnoses (12 to 18 years) and their parents participated in the study.
      Girls reported higher pain intensity within the last 7 days and 4 weeks despite
      similar diagnosis, physical status, duration of diagnoses, and main pain causes.
      When asked for pain intensity that dated back in time, parent and adolescent
      ratings diverged, with a trend for parents to reporting higher pain intensity in
      boys and lower pain intensity in girls, particularly for pain in the preceding 7
      days. The present study provides preliminary evidence for sex differences in the
      recalled pain experience of adolescents with malignant diagnoses. Although boys
      and girls experience present pain similarly and hence should be treated
      similarly, girls recall higher pain intensity than boys. Future studies should
      address whether negative memories in girls play a significant role and may have
      an impact on girls' well-being and pain-related distress. Additionally,
      psychosocial factors such as gender role expectations may need to be
      investigated. Parental variables and their impact on parents' pain ratings,
      especially for ratings of precedent pain, warrants further investigation.
      PERSPECTIVE: Girls with malignant diagnoses differ from boys in their recalled
      pain intensity ratings, with girls reporting higher pain intensity. Additional
      pain management strategies referring to the memory of pain may need to be
      implemented.

PMID- 19386553
TI  - Differential effect of capsaicin treatment on pain-related behaviors after
      plantar incision.
AB  - We evaluated the effect of infiltration of dilute solutions of capsaicin,
      administered before plantar incision, on 3 pain-related behaviors: guarding pain,
      heat-withdrawal latency, and mechanical-withdrawal threshold. Perineural
      application of capsaicin was also studied and the appearance of the wound was
      also evaluated. Dilute solutions of capsaicin .025% and .10% were infiltrated in
      the plantar region 1 day before incision. In another group of rats, perineural
      capsaicin (1%) was applied to the nerves innervating the plantar aspect of the
      rat hindpaw. Rats were then tested for pain-related behaviors before and after
      plantar incision and then daily thereafter. Wound appearance was graded and
      histopathology was evaluated. Infiltration with capsaicin reduced guarding pain
      and heat hyperalgesia after plantar incision; there were minimal effects on
      mechanical responses. Perineural-capsaicin application produced a similar result.
      Both capsaicin infiltration and perineural-capsaicin application impaired wound
      apposition. Histologic evaluation also confirmed impaired wound apposition after
      capsaicin infiltration. In conclusion, dilute solutions of capsaicin have
      differential effects on pain-related behaviors after plantar incision. Based on
      the antinociception produced by capsaicin both via infiltration and perineural
      injection, the effect on wound appearance was likely related to its inhibitory
      effects on pain behaviors and was not necessarily a local effect of the drug.
      PERSPECTIVE: This study demonstrated that capsaicin infiltration before plantar
      incision produced an analgesic effect that depended upon the stimulus modality
      tested. When evaluating novel treatments for postoperative pain, studies using a
      single stimulus modality may overlook an analgesic effect by not examining a
      variety of stimuli.

PMID- 19386555
TI  - In situ electrochemical and AFM study of thalidomide-DNA interaction.
AB  - The interaction of thalidomide (TD) with double-stranded DNA (dsDNA) was studied
      using atomic force microscopy (AFM) at highly oriented pyrolytic graphite (HOPG),
      differential pulse voltammetry (DPV) at glassy carbon electrodes (GCE), UV-Vis
      and electrophoresis. After incubation of dsDNA with different concentrations of
      TD, the AFM images show the formation of thin and incomplete TD-DNA network films
      with a number of embedded molecular aggregates and regions of uncovered HOPG.
      Both the TD-dsDNA aggregates and network thickness directly depended on the TD
      concentration and incubation time. The voltammetric data also showed that the
      modifications caused by TD to the DNA double helical structure are time
      dependent. In agreement with AFM, DPV, UV-Vis and electrophoresis results, a
      model is proposed for the TD-DNA interaction, considering that TD intercalates
      into the dsDNA, causing defects in the dsDNA secondary structure and DNA double
      helix unwinding. Moreover, both AFM and DPV show that condensation is caused to
      DNA by TD and occurs until 24 h of incubation, as well as DNA oxidative damage,
      detected electrochemically by the appearance of the 8-oxoGua and/or 2,8 oxoAde
      oxidation peak.

PMID- 19386556
TI  - Construction of a circular single-stranded DNA template containing a defined
      lesion.
AB  - We report a concise and efficient method to make a circular single-stranded DNA
      containing a defined DNA lesion. In this protocol, phagemid DNA containing Uracil
      is used as a template to synthesize a complementary DNA strand using T7 DNA
      polymerase and an oligonucleotide primer including a site-specific DNA lesion.
      The ligated lesion-containing strand can be recovered after the phage-derived
      template DNA is degraded by treatment with E. coli Uracil DNA glycosylase and
      Exonucleases I and III. The resulting product is a circular single-stranded DNA
      containing a defined DNA lesion suitable for in vitro translesion replication
      assays.

PMID- 19386557
TI  - Determination of endogenous thiols and thiol drugs in urine by HPLC with
      ultraviolet detection.
AB  - Analysis of urine for endogenous thiols and thiol drugs content by HPLC with
      ultraviolet detection is addressed. Other methodologies for detection and
      determination of thiols in urine are only mentioned. Outline of metabolism, role
      of main biological thiols in physiological and pathological processes and their
      reference concentrations in urine are presented. In particular, urine sample
      preparation procedures, including reduction of thiol disulfides, chemical
      derivatization and reversed-phase HPLC separation steps are discussed. Some
      experimental details of analytical procedures for determination of endogenous
      thiols cysteine, cysteinylglycine, homocysteine, N-acetylcysteine, thioglycolic
      acid; and thiol drugs cysteamine, tiopronin, D-penicillamine, captopril, mesna,
      methimazole, propylthiouracil and thioguanine are reviewed.

PMID- 19386558
TI  - Evicting hitchhiker antigens from purified antibodies.
AB  - Antibodies that target common cellular structures may have a propensity to bind
      those very same antigens as they become exposed in dead or dying cells during
      production in a bioreactor. Those tendencies can be accentuated if the targeted
      epitope is highly conserved across species. While attention to contaminants such
      as endotoxin, viral particles, cellular DNA and even prions has grown coincident
      with the emergence of the monoclonal antibody industry, it is surprising how
      little attention has been focused on hitchhiker antigens that may co-elute while
      bound to the supposedly pure antibody. In this case study, we will focus on anti
      histone antibodies and the measures we have taken to eliminate stowaways, such as
      histone-DNA complexes. These simple measures include the addition of a quartenary
      amine guard column to the protein A, adjusting the ionic strength of the cell
      culture supernatant to 400 mM sodium chloride, and establishing a mobile phase
      gradient from 400 mM to 2M during protein A chromatography. Initially adjusting
      the cell culture to 600 mM can compromise the quartenary amine guard column.
      Also, we demonstrate the applicability of these techniques in both the R&D lab
      and the manufacturing plant, particularly in improving the apparent potency of
      antibodies destined for the clinic. Given the prominence of anti-histone
      antibodies in chromatin immunoprecipitation (ChIP), the implications of
      hitchhiker antigens interferring with the results of an experiment are far
      reaching, indeed, we detect them in some popularly used antibodies. Moreover, a
      wide variety of monoclonals that may target antigens expressed by the producer
      cell line may face similar problems, resulting in a decreased production yield,
      as well as a diminished apparent binding potency.

PMID- 19386559
TI  - Sulfenic acid--a key intermediate in albumin thiol oxidation.
AB  - The single thiol of human serum albumin (HSA-SH) is the predominant plasma thiol.
      Both circulating albumin and pharmaceutical preparations are heterogeneous
      regarding the thiol redox status, as revealed by anion-exchange-hydrophobic
      interaction chromatography. Sulfenic acid (HSA-SOH) is an intermediate in HSA-SH
      oxidation processes that was detected through different techniques including mass
      spectrometry. Recently, quantitative data led to the determination of rate
      constants. The preferred fate of HSA-SOH is the formation of mixed disulfides.
      Alternatively, HSA-SOH can be further oxidized to sulfinic and sulfonic acids.
      Oxidized forms increase under disease conditions, underscoring the importance of
      HSA-SH as a plasma scavenger of intravascular oxidants. We here provide a
      critical review of the oxidation of HSA-SH in the context of the intravascular
      compartment, with emphasis in the methodological approaches of mass spectrometry
      and chromatography for the analysis of albumin thiol redox states.

PMID- 19386560
TI  - Optical coherence tomography in pediatric patients: a feasible technique for
      diagnosing celiac disease in children with villous atrophy.
AB  - BACKGROUND AND AIM: Celiac disease is a common condition with many atypical
      manifestations, where histology serves as the "gold standard" for diagnosis. A
      useful new technique, optical coherence tomography, can depict villous morphology
      in detail, using light waves. This study examined the correlation between the
      sensitivity and specificity of optical coherence tomography in pediatric patients
      undergoing esophago-gastro-duodenoscopy for the diagnosis of celiac disease.
      MATERIALS AND METHODS: A total of 134 children were prospectively enrolled, 67
      with a serological suspicion of celiac disease (group 1) and 67 with negative
      histology for celiac disease (group 2). During a diagnostic esophago-gastro
      duodenoscopy we acquired multiple images and films in the four quadrants of the
      second part of the duodenum, and biopsies were taken in the area where optical
      coherence tomography had been done. Three patterns of villous morphology were
      considered: pattern 1=no atrophy (types 0, 1 or 2 of the Marsh classification);
      pattern 2=mild atrophy (type 3a or 3b); pattern 3=marked atrophy (type 3c).
      RESULTS: The diagnosis of celiac disease was histologically confirmed in all 67
      children with positive antiendomysium and/or antitransglutaminase antibodies.
      Optical coherence tomography correlated with pattern 1 histology in 11/11 cases,
      pattern 2 in 30/32 (93.8%) and pattern 3 in 22/24 (91.6%). Sensitivity and
      specificity were 82% and 100%. In the control group there was 100% concordance
      between optical coherence tomography and histology. The overall concordance
      between optical coherence tomography and histology in determining patchy lesions
      was 75%. CONCLUSION: Optical coherence tomography could be a helpful diagnostic
      tool in children with mild or marked villous atrophy for diagnosing celiac
      disease during upper gastrointestinal (GI) endoscopy, avoiding biopsies. However,
      duodenal biopsies are mandatory if the optical coherence tomography shows normal
      villous morphology in patients with positive antibodies.

PMID- 19386561
TI  - A reverse flow cross finger pedicle skin flap from hemidorsum of finger.
AB  - A reverse-flow cross-finger pedicle skin flap raised from the hemidorsum has been
      used, which is a modification of the distally based dorsal cross-finger flap. The
      flap is raised from the hemidorsum at a plane above the paratenon, the distal
      most location of the base being at the level of the distal interphalangeal joint.
      Thirty-two flaps were used from as many fingers of as many patients. Of these, 31
      (97%) flaps survived fully; there was stiffness of finger in one (3%) patient and
      the two-point discrimination was 4-8mm (n=14). Follow-up period was 2 months to 3
      years, the median being 1 year and 3 months. The advantages of this flap are that
      there is less disruption of veins and less visible disfigurement of the dorsum of
      the finger when compared to other pedicled cross-finger skin flaps. The
      disadvantage of this flap is its restricted width. It is recommended as the cross
      finger pedicle skin flap of choice when the defect is not wide.

PMID- 19386562
TI  - Use of ligaclips in stopping microvascular anastomotic leaks.

PMID- 19386563
TI  - [An efficient strategy to decrease the central venous catheter-related adverse
      events rate in haemodialysis patients].
AB  - INTRODUCTION: Catheter-related adverse events (CAE) remain a major cause of
      mortality and morbidity. AIM: We aimed to compare the CAE prevalence and adverse
      events rate at 10 years interval in one centre using different devices, dressing
      procedures. METHODS: We compared two periods, from 1994 to 1997 (period 1) and
      from 2004 to 2007 (period 2). We recorded all prevalent tunnelled CAE and their
      related adverse event rate: catheter-related bacteraemia (CRB), catheter local
      infection (CLI), catheter dysfunction leading to CAE exchange, thrombolytic use
      and spontaneous pulling up. RESULTS: In period 1, PermCath catheter (Quinton,
      N=63) and TwinCath catheter (MedComp, N=76) were used in 95 HD. BioFlex catheter
      (N=52) and ASPC split catheter (MedComp, N=52) were used in 72 HD in period 2. In
      period 1, we performed catheter dressing using povidone iodine versus alcoholic
      chlorexidine in period 2. Between period 1 and period 2, the CAE prevalence
      decreased from 15-18% to 9-6%, CRB from 1.1 to 0.23/1000 day-catheter (p<0.001),
      CLI from 1.1 to 0.28/1000 day-catheter (p<0.001), definitive dysfunction from 12
      to 1.2% (p<0.001) and CAE pulling up from 4 to 0%. The annual urokinase
      consumption decreased from three to one unit per CAE. CONCLUSION: This study
      shows the dramatic decrease in CAE prevalence (-50%) and related-adverse events
      (approximately -200%) since 10 years. Switching povidone iodine to chlorexidine
      and using more recent catheter devices appear very efficient in decreasing
      catheter-related adverse events.

PMID- 19386564
TI  - [Surgical treatment for early Barrett cancer].
AB  - Adenocarcinomas in Barrett's oesophagus are more commonly diagnosed at an early
      stage due to effective surveillance programmes. Subtotal oesophagectomy with
      extended lymphadenectomy is considered the best curative treatment for patients
      with early adenocarcinoma of the oesophagus. However, such treatment carries
      substantial morbidity and compromises quality of life. Limited resection, minimal
      invasive surgical procedures or endoscopic mucosal ablation have been proposed as
      less invasive alternatives. A comparison of treatment associated morbidity,
      recurrence rate, long-term survival and functional outcome suggests that none of
      these alternative methods can be universally recommended. An individualized
      strategy should be employed based on staging (tumour penetration into the
      mucosa/submucosa, presence of lymph node metastasis), multicentricity, length of
      the underlying Barrett mucosa and risk factors of the patient. Surgical resection
      (radical or limited) remains the treatment of choice for tumours invading the
      submucosa, or multicentric and recurrent tumours after endoscopic mucosectomy.

PMID- 19386565
TI  - [Self-expanding metal stents for palliation of malignant oesophageal
      obstruction].
AB  - BACKGROUND: Malignant oesophageal stenosis can be caused by cancer of the
      oesophagus, gastric cardia, lungs, mediastinum or, rarely, breast. Most of these
      cases are inoperable due to advanced stage of the disease, comorbidities or age
      of the patients; and palliative treatment can be applied only. The quality of
      life is mostly determined by the extent of dysphagia. Several methods are
      available to palliate dysphagia. Hereby, the authors review their results with
      palliation of malignant oesophageal obstruction applying self-expanding metal
      stents. PATIENTS AND METHODS: 68 endoscopic stent implantations were performed in
      64 patients (15 female and 49 male) with malignant dysphagia between 2003 and
      2008. After radiological investigations, distally deployed covered stents with or
      without an antireflux valve were placed, depending on the localization of the
      tumour. In one patient with a stenosis localized in the upper third of the
      oesophagus a proximally deployed covered stent was used. The aim was to re
      establish oral nutrition and cover possible fistulas. RESULTS: Significant
      improvement of swallowing was detected in every patient. Average dysphagia score
      has improved from 3.2 to 1.7. Technical difficulties during stenting occurred in
      a relatively low percentage of patients only (2 in 68; i.e. 2.94%). Fistulas were
      covered in every case. Early stent migration (<7 days) happened in one case. One
      patient suffered non-fatal myocardial infarction two days after stent placement.
      In 5 cases tumour in- and overgrowth, in 4 cases bleeding was seen as late
      complications. Oesophago-tracheal fistula was noted in three patients after stent
      implantation. Late stent migration (>7 days) occurred in two patients. Re
      stenting was necessary in four cases, while three patients needed an upper GI
      endoscopy for cleansing the stent caused by food obstruction. CONCLUSIONS:
      According to our data self-expanding metal stents are highly effective and safe
      for improving dysphagia. Stent-related complications are relatively rare. This
      method is highly recommended for palliation of malignant dysphagia.

PMID- 19386566
TI  - [Osteosynthesis with plates for full sternal dehiscence (Titanium Sternal
      Fixation System Synthes) -- first use in Hungary].
AB  - The prevalence of deep sternal infection after cardiac surgery is between 0,5 and
      5%, with an average mortality up to 50%. The authors present the case of the rst
      sternal osteosynthesis carried out in Hungary after postoperative deep sternal
      infection. Using this orthopedic reconstructive surgical technique in this
      patient group, an anatomical reconstruction and reposition of the sternum is
      feasible. With the Titanium Sternal Fixation Synthes system reconstruction of
      total or partial sternal absence is possible.

PMID- 19386567
TI  - [Development of scar cancer after subtotal oesophagectomy for corrosive injury].
AB  - INTRODUCTION: The incidence of cicatricial carcinoma of the scarred esophagus in
      patients with corrosive injuries is relatively high. Therefore, the necessity to
      resect the diseased oesophagus was raised as opposed to carry out a simple by
      pass reconstruction only. CASE REPORT: A 56-year-old female patient with a past
      medical history of lye consumption presented with a stricture of the esophagus.
      She underwent resection of the diseased esophagus with mediastinal colon
      interposition. 28 years after surgery the patient had symptoms of progressive
      dysphagia and loss of weight caused by scar cancer of the esophagus. After
      neoadjuvant chemo-radiotherapy, resection of the remainder oesophagus was
      performed with free jejunal transplantation. On postoperative day 14 the patient
      had been discharged with no complications and good swallowing function.
      CONCLUSION: In our case, scar cancer developed 28 years after oesophageal
      resection and more than 50 years after the corrosive injury. This case is another
      argument for simple bypass.

PMID- 19386568
TI  - [Long-term experience with therapy of a female patient with Gardner's syndrome,
      first presenting with extra-abdominal desmoid tumor, and review of the
      literature].
AB  - Gardner's syndrome is a clinical subgroup of familial adenomatous polyposis, an
      autosomal dominant disease. It is characterized by gastrointestinal polyps and
      extra-intestinal manifestations including multiple osteomas, skin and soft tissue
      tumours. Aggressive desmoid tumours can be very difficult to manage in patients
      with Gardner's syndrome. We present a case of a 17-year-old female who presented
      with an aggressive desmoid tumor arising of the lumbar area as part of her
      Gardner's syndrome. She was treated with surgery, nonsteroidal anti-inflammatory
      drugs, tamoxifen and radiotherapy, and was followed up for 80 months. We conclude
      that desmoid tumors can precede gastrointestinal manifestations of familial
      adenomatous polyposis or Gardner's syndrome. Such patients should be evaluated
      with genetic testing followed by colonoscopy. Desmoid tumours should be managed
      in a multidisciplinary setting, as well.

PMID- 19386569
TI  - [Surgical treatment of primary leiomyosarcoma of the inferior vena cava].
AB  - CASE REPORT: pLMS in the wall of the inferior vena cava is an extremely rare form
      of retroperitoneal malignancies. A case in a young female patient is presented;
      clinical symptoms, pre- and postoperative diagnosis and surgical treatment are
      discussed. A retroperitoneal mass detected by imaging was found to be a large
      tumor mass located at the middle segment of the IVC on exploration. The tumour
      was successfully excised and the IVC was reconstructed with a synthetic graft.
      Eight years later, this patient needed a repeat surgery due to local recurrence.
      This time tumour was attached to the left renal vein. A re-resection of the IVC
      was performed with subsequent synthetic graft reconstruction and the distal end
      of the left renal vein was reimplanted into a lower segment of IVC. DISCUSSION:
      Primary leiomyosarcoma of the inferior vena cava (pLMS-IVC) is an extremely rare
      form of retroperitoneal malignancies. The tumour arises from the medial layer of
      the venous wall and can grow either intraluminally, or extraluminally or in both
      directions, as well. It can be localized in the first segment of IVC (above the
      hepatic veins), in the second segment between hepatic and renal veins and finally
      in the third segment between the right common iliac vein and renal veins.
      Therefore, the tumour can infiltrate both hepatic and/or renal vessels. Upper
      segment tumours can cause Budd-Chiari syndrome (hepatomegaly, abdominal pain,
      jaundice and ascites) with a bad prognosis. Middle segment tumours usually
      present with right upper quadrant pain, or may mimic biliary tract disease with a
      much better prognosis. Accumulating experience suggests that radio-chemotherapy
      alone seems to be less effective than "en bloc" resection with clear margins
      including loco-regional lymph nodes. Therefore, our choice of treatment was the
      latter. Although radical resection can be carried out in most of cases, 50% of
      patients develop a late recurrence yet.

PMID- 19386570
TI  - [Our experience with the incidence of hereditary non-polyposis colorectal
      cancer].
AB  - INTRODUCTION: Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is the most
      frequent genetic disease leading to colorectal malignancies. 3-5 percent of all
      colorectal cancer cases are related to Hereditary Non-Polyposis Colorectal
      Cancer. Currently there is no reliable data on the incidence of the disease in
      Hungary. METHODS: The family history of 809 patients with colorectal cancer was
      investigated between 1997 and 2006. Data collection was performed in a
      retrospective manner in the rst and in a prospective manner in the second phase
      of the study. Subsequent immunohistochemical and microsatellite instability
      analysis, and DNA sequencing was carried out to detect any underlying MMR gene
      mutation. Moreover, multiple ligation dependent probe amplication was applied for
      recognizing large deletions in MMR genes. RESULTS: During the investigation 10
      pathogenic mutations and several polymorphisms were found. Seven mutations were
      detected in families fulfilling the Amsterdam Criteria, while the remaining three
      fulfilled the Bethesda Criteria. In the second phase of the study -- which better
      reflects the real population characteristics -- six percent of our patients
      fulfilled completely the Amsterdam Criteria and we managed to nd pathogenic MMR
      gene mutations in 1,7 percent of our patients. CONCLUSION: 8 out of 10 pathogenic
      mutations were novel and published rst time by ourselves. No repeatedly occurring
      mutations were found in our patients. It seems that these genetic alterations are
      located sporadically on different exons of the involved MMR genes. Our mutation
      detection rate was 77 percent in the Amsterdam positive patients who were
      completely examined, which appears to be better than the published data in the
      relevant literature. Importantly, 30 percent of the mutation carrier could be
      missed applying only this single criteria system. In order to detect the highest
      number of HNPCC patients, we suggest using both the Amsterdam as well as the
      Bethesda Criteria.

PMID- 19386571
TI  - [Gyorgy Berci--88 years of age].

PMID- 19386574
TI  - Body weight dynamics and their association with physical function and mortality
      in older adults: the Cardiovascular Health Study.
AB  - BACKGROUND: To estimate the associations of weight dynamics with physical
      functioning and mortality in older adults. METHODS: Longitudinal cohort study
      using prospectively collected data on weight, physical function, and health
      status in four U.S. Communities in the Cardiovascular Health Study. Included were
      3,278 participants (2,013 women and 541 African Americans), aged 65 or older at
      enrollment, who had at least five weight measurements. Weight was measured at
      annual clinic visits between 1992 and 1999, and summary measures of mean weight,
      coefficient of variation, average annual weight change, and episodes of loss and
      gain (cycling) were calculated. Participants were followed from 1999 to 2006 for
      activities of daily living (ADL) difficulty, incident mobility limitations, and
      mortality. RESULTS: Higher mean weight, weight variability, and weight cycling
      increased the risk of new onset of ADL difficulties and mobility limitations.
      After adjustment for risk factors, the hazard ratio (95% confidence interval) for
      weight cycling for incident ADL impairment was 1.28 (1.12, 1.47), similar to that
      for several comorbidities in our model, including cancer and diabetes. Lower
      weight, weight loss, higher variability, and weight cycling were all risk factors
      for mortality, after adjustment for demographic risk factors, height, self-report
      health status, and comorbidities. CONCLUSIONS: Variations in weight are important
      indicators of future physical limitations and mortality in the elderly and may
      reflect difficulties in maintaining homeostasis throughout older ages. Monitoring
      the weight of an older person for fluctuations or episodes of both loss and gain
      is an important aspect of geriatric care.

PMID- 19386575
TI  - Localization of brain white matter hyperintensities and urinary incontinence in
      community-dwelling older adults.
AB  - BACKGROUND: Because white matter hyperintensities (WMHs) on magnetic resonance
      imaging (MRI) may be linked to geriatric syndromes involving mobility, cognition,
      and affect, we postulated that involvement of areas critical to bladder control
      could influence urinary incontinence (UI). METHODS: One hundred community
      dwelling individuals (75-89 years) were recruited into three groups stratified by
      age and gender reflecting normal and mildly and moderately impaired mobility.
      Baseline incontinence status and related symptoms were evaluated in 97
      individuals using validated instruments (3IQ, Urinary Incontinence Severity
      Index, Urogenital Distress Inventory, Incontinence Impact Questionnaire).
      Regional WMH was measured using an MRI brain imaging segmentation pipeline and WM
      tract-based parcellation atlas. RESULTS: Sixty-two (64%) of the participants were
      incontinent, mostly with urgency (37; 60%) and moderate-severe symptoms (36;
      58%). Incontinent individuals were more likely to be women with worse scores for
      depression and mobility. WMH located in right inferior frontal regions predicted
      UI severity, with no significant relationship with incontinence, incontinence
      type, bother, or functional impact. As regards WM tracts, WMH within regions
      normally occupied by the anterior corona radiata predicted severity and degree of
      bother, cingulate gyrus predicted incontinence and severity, whereas cingulate
      (hippocampal portion) and superior fronto-occipital fasciculus predicted
      severity. CONCLUSIONS: Presence of WMH in right inferior frontal regions and
      selected WM tracts predicts incontinence, incontinence severity, and degree of
      bother. Our observations support the findings of recent functional MRI studies
      indicating a critical role for the cingulum in bladder control, while also
      suggesting potential involvement of other nearby WM tracts such as anterior
      corona radiata and superior fronto-occipital fasciculus.

PMID- 19386576
TI  - Rate of cannabis use disorders in clinical samples of patients with
      schizophrenia: a meta-analysis.
AB  - OBJECTIVE: Our aim was to review recent studies and estimate the rate of cannabis
      use disorders (CUDs) in schizophrenia, as well as to examine the factors
      affecting this rate. METHODS: We conducted an electronic search of 3 literature
      databases and a manual search of articles from 1996 to 2008. The key words used
      were "schizophreni*," "psychos*s," "psychotic," "cannabis abuse," "cannabis
      dependence," "cannabis use disorder," "substance use disorder," "substance
      abuse," "substance dependence," and "dual diagnosis." Articles that reported
      diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders
      or International Classification of Diseases were included. Regression analysis
      was used to examine how estimated rates of CUDs are affected by various study
      characteristics such as the classification system, inpatient vs outpatient
      status, study location, proportion of males, age of the sample, or duration of
      illness. RESULTS: Thirty-five studies met our search criteria. The median current
      rate of CUDs was 16.0% (interquartile range [IQR] = 8.6-28.6, 10 studies), and
      the median lifetime rate was 27.1% (IQR = 12.2-38.5, 28 studies). The median rate
      of CUDs was markedly higher in first-episode vs long-term patients (current
      28.6%/22.0%, lifetime 44.4%/12.2%, respectively) and in studies where more than
      two-thirds of the participants were males than in the other studies
      (33.8%/13.2%). CUDs were also more common in younger samples than in the others
      (current 38.5%/16.0%, lifetime 45.0%/17.9%). CONCLUSIONS: Approximately every
      fourth schizophrenia patient in our sample of studies had a diagnosis of CUDs.
      CUDs were especially common in younger and first-episode patient samples as well
      as in samples with a high proportion of males.

PMID- 19386577
TI  - Intrinsic motivation inventory: an adapted measure for schizophrenia research.
AB  - This article describes the psychometric validation of a scale designed to measure
      intrinsic motivation (IM) in schizophrenia. Recent studies have highlighted the
      relationship between motivation and functional outcome in schizophrenia and
      identified IM as an important mediating factor between neurocognition and
      psychosocial outcome. It therefore becomes imperative to have validated measures
      of IM for empirical use. To that end, we validated a self-report IM scale that
      gauges the central motivational structures identified by Self-determinism Theory
      as pertinent to cognitive task engagement, skill acquisition, treatment
      compliance, and remediation outcome. Participants were schizophrenia outpatients
      involved in a cognitive remediation study (n = 58), a convenience subsample of
      clinically stable schizophrenia outpatients (n = 15), and a group of healthy
      normals (n = 22). The Intrinsic Motivation Inventory for Schizophrenia Research
      (IMI-SR) is a concise instrument, possessing good internal consistency (alpha =
      .92) and test-retest reliability (intraclass correlation = .77). Data were
      analyzed to abridge the original 54 items into a final 21-item questionnaire
      comprised of 3 domains relevant to motivation for treatments (interest/enjoyment,
      perceived choice, value/usefulness). The scale was highly associated with germane
      constructs of motivation for health-related behaviors, including perceived
      competency for attempting challenging tasks and autonomous treatment engagement.
      Importantly, the scale was able to distinguish improvers and nonimprovers on a
      cognitive task and actual learning exercises, delineate high vs low treatment
      attendance, and demonstrate sensitivity to motivational changes due to
      intervention variation. The IMI-SR is a viable instrument to measure IM in
      schizophrenia as part of a cognitive remediation protocol or psychosocial
      rehabilitation program.

PMID- 19386578
TI  - Validity of the prodromal risk syndrome for first psychosis: findings from the
      North American Prodrome Longitudinal Study.
AB  - Treatment and prevention studies over the past decade have enrolled patients
      believed to be at risk for future psychosis. These patients were considered at
      risk for psychosis by virtue of meeting research criteria derived from
      retrospective accounts of the psychosis prodrome. This study evaluated the
      diagnostic validity of the prospective "prodromal risk syndrome" construct.
      Patients assessed by the Structured Interview for Prodromal Syndromes as meeting
      criteria of prodromal syndromes (n = 377) from the North American Prodrome
      Longitudinal Study were compared with normal comparison (NC, n = 196), help
      seeking comparison (HSC, n = 198), familial high-risk (FHR, n = 40), and
      schizotypal personality disorder (SPD, n = 49) groups. Comparisons were made on
      variables from cross-sectional demographic, symptom, functional, comorbid
      diagnostic, and family history domains of assessment as well as on follow-up
      outcome. Prodromal risk syndrome patients as a group were robustly distinguished
      from NC subjects across all domains and distinguished from HSC subjects and from
      FHR subjects on most measures in many of these domains. Adolescent and young
      adult SPD patients, while distinct from prodromal patients on definitional
      grounds, were similar to prodromals on multiple measures, consistent with SPD in
      young patients possibly being an independent risk syndrome for psychosis. The
      strong evidence of diagnostic validity for the prodromal risk syndrome for first
      psychosis raises the question of its evaluation for inclusion in Diagnostic and
      Statistical Manual of Mental Disorders (Fifth Edition).

PMID- 19386579
TI  - Pretreatment and outcome correlates of sexual and physical trauma in an
      epidemiological cohort of first-episode psychosis patients.
AB  - OBJECTIVES: High prevalence of trauma has been reported in psychosis. While role
      of trauma as a risk factor for developing psychosis is still debated, its
      negative impact on outcome has been described. Few studies have explored this
      issue in first-episode psychosis (FEP) patients. We assessed rate of stressful
      events, as well as premorbid and outcome correlates of past sexual and/or
      physical abuse (SPA) in an epidemiological FEP patients cohort. METHODS: The
      Early Psychosis Prevention and Intervention Centre admitted 786 FEP patients
      between 1998 and 2000. Data were collected from patients' files using a
      standardized questionnaire. A total of 704 files were available, 43 excluded
      because of a nonpsychotic diagnosis at end point and 3 due to missing data
      regarding past stressful events; 658 patients were analyzed. RESULTS: A total of
      83% patients had been exposed to at least one stressful event and 34% to SPA. SPA
      patients were more likely to have presented other psychiatric disorders before
      psychosis onset (posttraumatic stress disorder, substance use disorder), to have
      made suicide attempts in the past, and to have had poorer premorbid functional
      levels. Additionally, SPA patients had higher rate of comorbid diagnosis at
      program entry and were more likely to attempt suicide during treatment.
      CONCLUSIONS: SPA prevalence is high in FEP patients and must be explored by
      clinicians considering its durable impact on psychological balance and link with
      long-lasting suicidal risk. More research is warranted to better understand
      mechanisms involved between trauma and its potential consequences, as well as to
      develop psychological interventions adapted to this very sensitive and complex
      issue.

PMID- 19386580
TI  - Novel variants of muscle calpain 3 identified in human melanoma cells: cisplatin
      induced changes in vitro and differential expression in melanocytic lesions.
AB  - Calpains are cysteine proteases comprising members ubiquitously expressed in
      human tissues and other tissue-specific isoforms. Alterations of calpain 3 (p94),
      the muscle-specific isoform that contains three peculiar sequences (NS, IS1 and
      IS2), are strictly associated to the limb-girdle muscular dystrophy type 2A, in
      which a myonuclear apoptosis has been documented. Our recent demonstration of a
      proapoptotic role of ubiquitous calpains in drug-induced apoptosis of melanoma
      cells prompted us to investigate the expression of calpain 3 in human melanoma
      cell lines undergoing apoptosis and in melanocytic lesions. In melanoma cell
      lines, we have identified two novel splicing variants of calpain 3 (hMp78 and
      hMp84): they have an atypical initiation exon and a putative nuclear localization
      signal, the shorter one lacks IS1 inset and both proteins are extremely unstable.
      Virtually, both isoforms (prevalently as cleavage forms) are localized in
      cytoplasm and in nucleoli. In cisplatin-treated preapoptotic cells, an increase
      of both transcription and autoproteolytic cleavage of the novel variants is
      observed; the latter event is prevented by the inhibitor of ubiquitous calpains,
      calpeptin, which is also able to protect from apoptosis. Interestingly, among
      melanocytic lesions, the expression of these novel variants is significantly
      downregulated, compared with benign nevi, in the most aggressive ones, i.e. in
      vertical growth phase melanoma and, even more, in metastatic melanoma cells,
      characterized by invasiveness properties and usually highly resistant to
      apoptosis. On the whole, our observations suggest that calpain 3 variants can
      play a proapoptotic role in melanoma cells and its downregulation, as observed in
      highly aggressive lesions, could contribute to melanoma progression.

PMID- 19386582
TI  - Does early review by a respiratory physician lead to a shorter length of stay for
      patients with non-severe community-acquired pneumonia?
AB  - BACKGROUND: The aim of this study was to evaluate whether patients with non
      severe community-acquired pneumonia (CAP) have a shorter length of stay (LOS)
      when initially seen by a respiratory physician compared with a non-respiratory
      physician. METHODS: At Nottingham City Hospital, following nurse triage, acute
      medical patients who are not severely ill are admitted to the consultant-led
      emergency short stay unit (ESSU). Records of patients seen on ESSU between
      January 2004 and December 2007 with a clinical discharge code relating to CAP
      were retrospectively examined. Patients with a diagnosis of cellulitis over the
      same time period were used as controls. Patients were grouped depending on
      whether they were seen on their first post-take ward round by a respiratory
      consultant physician (group A), non-respiratory consultant physician (group B) or
      on a Saturday or Sunday (group C). RESULTS: Following exclusions, 426 patients
      with CAP and 935 patients with cellulitis were analysed. The median LOS for
      patients with CAP in group A was 1.74 days (n = 123, interquartile range (IQR)
      0.97-4.09) compared with 3.03 days for patients in group B (n = 174, IQR 1.12
      6.23; p<0.01). There was a larger percentage of discharges within 24 h of
      consultant review in group A (43.1%) compared with group B (31.9%), although this
      was not statistically significant (p = 0.18). There was no statistically
      significant difference between groups A and B with cellulitis in LOS or
      percentage discharged within 24 h of first consultant review. CONCLUSION:
      Patients with non-severe CAP have a shorter hospital LOS when initially seen by a
      respiratory compared with a non-respiratory physician.

PMID- 19386581
TI  - Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet
      distinct gene expression profiles between Keap1 knockout and triterpenoid-treated
      mice.
AB  - Loss of NF-E2-related factor 2 (Nrf2) signaling increases susceptibility to acute
      toxicity, inflammation and carcinogenesis in mice due to the inability to mount
      adaptive responses. In contrast, disruption of Keap1 (a cytoplasmic modifier of
      Nrf2 turnover) protects against these stresses in mice, although inactivating
      mutations in Keap1 have been identified recently in some human cancers. Global
      characterization of Nrf2 activation is important to exploit this pathway for
      chemoprevention in healthy, yet at-risk individuals and also to elucidate the
      consequences of hijacking the pathway in Keap1-mutant human cancers. Liver
      targeted conditional Keap1-null, Albumin-Cre:Keap1((flox/-)) (CKO) mice provide a
      model of genetic activation of Nrf2 signaling. By coupling global gene expression
      analysis of CKO mice with analysis of pharmacologic activation using the
      synthetic oleanane triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28
      oyl]imidazole (CDDO-Im), we are able to gain insight into pathways affected by
      Nrf2 activation. CDDO-Im is an extremely potent activator of Nrf2 signaling. CKO
      mice were used to identify genes modulated by genetic activation of Nrf2
      signaling. The CKO response was compared with hepatic global gene expression
      changes in wild-type mice treated with CDDO-Im at a maximal Nrf2 activating dose.
      The results show that genetic and pharmacologic activation of Nrf2 signaling
      modulates pathways beyond detoxication and cytoprotection, with the largest
      cluster of genes associated with lipid metabolism. Genetic activation of Nrf2
      results in much larger numbers of detoxication and lipid metabolism gene changes.
      Additionally, analysis of pharmacologic activation suggests that Nrf2 is the
      primary mediator of CDDO-Im activity, though other cell-signaling targets are
      also modulated following an oral dose of 30 micromol/kg.

PMID- 19386583
TI  - Validation and clinical implications of the IDSA/ATS minor criteria for severe
      community-acquired pneumonia.
AB  - BACKGROUND: The 2007 Infectious Disease Society of America (IDSA)/American
      Thoracic Society (ATS) guidelines defined severe community-acquired pneumonia
      (CAP) and recommended intensive care unit (ICU) admission when patients fulfilled
      three out of nine minor criteria. These criteria have not been validated.
      METHODS: All patients admitted to our hospital from 2004 to 2007 for CAP were
      reviewed retrospectively. Patients who fulfilled any IDSA/ATS major criteria for
      severe CAP at the emergency department (ie, the need for mechanical ventilation
      or vasopressors) were excluded. The predictive characteristics of the IDSA/ATS
      minor criteria were compared with those of the Pneumonia Severity Index (PSI) and
      the CURB-65 score for hospital mortality and ICU admission. RESULTS: 1242
      patients were studied (mean age 65.7 years, hospital mortality 14.7%). The areas
      under the receiver operating characteristic curves for the IDSA/ATS minor
      criteria were 0.88 (95% CI 0.86 to 0.91) and 0.85 (95% CI 0.81 to 0.88) for
      predicting hospital mortality and ICU admission, respectively. These were greater
      than the corresponding areas for the PSI and the CURB-65 score (p < 0.05). The
      sensitivity, specificity, positive and negative predictive values of the minor
      criteria were 81.4%, 82.9%, 45.2% and 96.3%, respectively, for hospital mortality
      and 58.3%, 90.6%, 52.9% and 92.3%, respectively, for ICU admission. The minor
      criteria were more specific than the PSI and more sensitive than the CURB-65
      score for both outcomes. CONCLUSION: These findings support the use of the
      IDSA/ATS minor criteria to predict hospital mortality and guide ICU admission in
      inpatients with CAP who do not require emergency mechanical ventilation or
      vasopressors.

PMID- 19386584
TI  - The PHF11 gene is not associated with asthma or asthma phenotypes in two
      independent populations.
AB  - BACKGROUND: Numerous areas of the human genome have previously been associated
      with asthma and asthma-related phenotypes, but few positive findings have been
      successfully replicated in independent populations. Initial studies have reported
      strong associations of variants in the plant homeodomain zinc finger protein 11
      (PHF11) gene with serum IgE levels, asthma, airway hyper-responsiveness and
      childhood atopic dermatitis. OBJECTIVES: To investigate the association of
      variants in the PHF11 gene with asthma and associated intermediate phenotypes in
      two independent Western Australian population-based samples. METHODS: A linkage
      disequilibrium (LD)-tagging set of 20 single nucleotide polymorphisms (SNPs) was
      genotyped in PHF11 in two separate populations (total n = 2315), a family-based
      twin study consisting of 230 families (n = 992 subjects) and a population-based
      nested case-control study consisting of 617 asthma cases and 706 controls.
      Information regarding asthma, respiratory physiology, atopy and environmental
      exposures was collected. Transmission disequilibrium tests, variance components
      models and generalised linear models were used to test for association between
      PHF11 SNPs and selected asthma outcomes (including longitudinal change in lung
      function). RESULTS: After correction for multiple testing, no statistically
      significant (p < 0.05) associations were found between PHF11 and either asthma or
      total serum IgE levels in either population. No statistically significant
      associations were found with any other asthma-associated phenotypes in either
      population. CONCLUSIONS: Previously reported associations of PHF11 with asthma
      outcomes were not replicated in this study. This study suggests that PHF11 is
      unlikely to contain polymorphic loci that have a major impact on asthma
      susceptibility in our populations.

PMID- 19386585
TI  - Qualitative aspects of breathlessness in health and disease.
AB  - BACKGROUND: Patients with respiratory disease use many different expressions to
      describe the sensation they experience as breathlessness. Although previous
      analyses have identified multiple dimensions of breathlessness, there is little
      agreement about their number and nature. This study has applied a novel approach,
      principal component analysis (PCA), to understanding descriptions of
      breathlessness in health and disease and extracting representative components.
      METHODS: 202 patients (asthma n = 60, chronic obstructive pulmonary disease n =
      65, interstitial lung disease n = 41, idiopathic hyperventilation n = 36) and 30
      healthy volunteers were studied. All subjects performed spirometry and gave
      binary responses to 45 descriptions recalling their experience of breathlessness
      at the end of exercise; patients repeated this for resting breathlessness. PCA
      identified response patterns in the questionnaire data and extracted
      discriminatory components. Component scores were calculated for each individual
      using the regression method. RESULTS: PCA identified six distinct components of
      breathlessness on exercise, explaining 62.8% of the variance: (1) air hunger, (2)
      affective, (3) nociceptive, (4) regulation, (5) attention and (6) miscellaneous
      qualities. Rest components explaining 63.1% of variance were (1) affective, (2)
      air hunger, (3) nociceptive, (4) wheeze, (5) regulation and (6) miscellaneous.
      Components identified on exercise differed significantly between disease groups
      and controls and were related to percentage predicted forced vital capacity.
      CONCLUSION: This analysis suggests that air hunger is the dominant sensation
      during exercise, while affective distress characterises resting breathlessness in
      patients with a range of respiratory disorders including idiopathic
      hyperventilation where lung mechanics are normal. This suggests that common
      mechanisms operate in qualitative aspects of breathlessness.

PMID- 19386586
TI  - Neural respiratory drive in obesity.
AB  - BACKGROUND: The load imposed on ventilation by increased body mass contributes to
      the respiratory symptoms caused by obesity. A study was conducted to quantify
      ventilatory load and respiratory drive in obesity in both the upright and supine
      postures. METHODS: Resting breathing when seated and supine was studied in 30
      obese subjects (mean (SD) body mass index (BMI) 42.8 (8.6) kg/m(2)) and 30 normal
      subjects (mean (SD) BMI 23.6 (3.7) kg/m(2)), recording the electromyogram of the
      diaphragm (EMGdi, transoesophageal multipair electrode), gastric and oesophageal
      pressures. RESULTS: Ventilatory load and neural drive were higher in the obese
      group as judged by the EMGdi (21.9 (9.0) vs 8.4 (4.0)%max, p<0.001) and
      oesophageal pressure swings (9.6 (2.9) vs 5.3 (2.2) cm H(2)O, p<0.001). The
      supine posture caused an increase in oesophageal pressure swings to 16.0 (5.0) cm
      H(2)O in obese subjects (p<0.001) and to 6.9 (2.0) cm H(2)O in non-obese subjects
      (p<0.001). The EMGdi increased in the obese group to 24.7 (8.2)%max (p<0.001) but
      remained the same in non-obese subjects (7.0 (3.4)%max, p = NS). Obese subjects
      developed intrinsic positive end-expiratory pressure (PEEPi) of 5.3 (3.6) cm
      H(2)O when supine. Applying continuous positive airway pressure (CPAP) in a
      subgroup of obese subjects when supine reduced the EMGdi by 40%, inspiratory
      pressure swings by 25% and largely abolished PEEPi (4.1 (2.7) vs 0.8 (0.4) cm
      H(2)O, p = 0.009). CONCLUSION: Obese patients have substantially increased neural
      drive related to BMI and develop PEEPi when supine. CPAP abolishes PEEPi and
      reduces neural respiratory drive in these patients. These findings highlight the
      adverse respiratory consequences of obesity and have implications for the
      clinical management of patients, particularly where the supine posture is
      required.

PMID- 19386587
TI  - Dual targeting of a tRNAAsp requires two different aspartyl-tRNA synthetases in
      Trypanosoma brucei.
AB  - The mitochondrion of the parasitic protozoon Trypanosoma brucei does not encode
      any tRNAs. This deficiency is compensated for by partial import of nearly all of
      its cytosolic tRNAs. Most trypanosomal aminoacyl-tRNA synthetases are encoded by
      single copy genes, suggesting the use of the same enzyme in the cytosol and in
      the mitochondrion. However, the T. brucei genome encodes two distinct genes for
      eukaryotic aspartyl-tRNA synthetase (AspRS), although the cell has a single
      tRNAAsp isoacceptor only. Phylogenetic analysis showed that the two T. brucei
      AspRSs evolved from a duplication early in kinetoplastid evolution and also
      revealed that eight other major duplications of AspRS occurred in the eukaryotic
      domain. RNA interference analysis established that both Tb-AspRS1 and Tb-AspRS2
      are essential for growth and required for cytosolic and mitochondrial Asp-tRNAAsp
      formation, respectively. In vitro charging assays demonstrated that the
      mitochondrial Tb-AspRS2 aminoacylates both cytosolic and mitochondrial tRNAAsp,
      whereas the cytosolic Tb-AspRS1 selectively recognizes cytosolic but not
      mitochondrial tRNAAsp. This indicates that cytosolic and mitochondrial tRNAAsp,
      although derived from the same nuclear gene, are physically different, most
      likely due to a mitochondria-specific nucleotide modification. Mitochondrial Tb
      AspRS2 defines a novel group of eukaryotic AspRSs with an expanded substrate
      specificity that are restricted to trypanosomatids and therefore may be exploited
      as a novel drug target.

PMID- 19386588
TI  - MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by
      down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non
      integrin (DC-SIGN).
AB  - MicroRNA-155 (miR-155) has been involved in the response to inflammation in
      macrophages and lymphocytes. Here we show how miR-155 participates in the
      maturation of human dendritic cells (DC) and modulates pathogen binding by down
      regulating DC-specific intercellular adhesion molecule-3 grabbing non-integrin
      (DC-SIGN), after directly targeting the transcription factor PU.1. During the
      maturation of DCs, miR-155 increases up to 130-fold, whereas PU.1 protein levels
      decrease accordingly. We establish that human PU.1 is a direct target for miR-155
      and localize the target sequence for miR-155 in the 3'-untranslated region of
      PU.1. Also, overexpression of miR-155 in the THP1 monocytic cell line decreases
      PU.1 protein levels and DC-SIGN at both the mRNA and protein levels. We prove a
      link between the down-regulation of PU.1 and reduced transcriptional activity of
      the DC-SIGN promoter, which is likely to be the basis for its reduced mRNA
      expression, after miR-155 overexpression. Finally, we show that, by reducing DC
      SIGN in the cellular membrane, miR-155 is involved in regulating pathogen binding
      as dendritic cells exhibited the lower binding capacity for fungi and HIV protein
      gp-120 when the levels of miR-155 were higher. Thus, our results suggest a
      mechanism by which miR-155 regulates proteins involved in the cellular immune
      response against pathogens that could have clinical implications in the way
      pathogens enter the human organism.

PMID- 19386589
TI  - Nuclear factor I-C is essential for odontogenic cell proliferation and
      odontoblast differentiation during tooth root development.
AB  - Our previous studies have demonstrated that nuclear factor I-C (NFI-C) null mice
      developed short molar roots that contain aberrant odontoblasts and abnormal
      dentin formation. Based on these findings, we performed studies to elucidate the
      function of NFI-C in odontoblasts. Initial studies demonstrated that aberrant
      odontoblasts become dissociated and trapped in an osteodentin-like mineralized
      tissue. Abnormal odontoblasts exhibit strong bone sialoprotein expression but a
      decreased level of dentin sialophosphoprotein expression when compared with wild
      type odontoblasts. Loss of Nfic results in an increase in p-Smad2/3 expression in
      aberrant odontoblasts and pulp cells in the subodontoblastic layer in vivo and
      primary pulp cells from Nfic-deficient mice in vitro. Cell proliferation analysis
      of both cervical loop and ectomesenchymal cells of the Nfic-deficient mice
      revealed significantly decreased proliferative activity compared with wild type
      mice. In addition, Nfic-deficient primary pulp cells showed increased expression
      of p21 and p16 but decreased expression of cyclin D1 and cyclin B1, strongly
      suggesting cell growth arrest caused by a lack of Nfic activity. Analysis of the
      pulp and abnormal dentin in Nfic-deficient mice revealed an increase in apoptotic
      activity. Further, Nfic-deficient primary pulp cells exhibited an increase in
      caspase-8 and -3 activation, whereas the cleaved form of Bid was hardly detected.
      These results indicate that the loss of Nfic leads to the suppression of
      odontogenic cell proliferation and differentiation and induces apoptosis of
      aberrant odontoblasts during root formation, thereby contributing to the
      formation of short roots.

PMID- 19386590
TI  - Meningioma 1 is required for appropriate osteoblast proliferation, motility,
      differentiation, and function.
AB  - The vitamin D endocrine system is essential for calcium and phosphate homeostasis
      and skeletal mineralization. The 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))
      hormone binds to the vitamin D receptor (VDR) to regulate gene expression. These
      gene products in turn mediate the actions of 1,25(OH)(2)D(3) in mineral
      regulating target cells such as the osteoblast. We showed previously that
      meningioma 1 (MN1) is a novel target of 1,25(OH)(2)D(3) in MG-63 osteoblastic
      cells and that it is a coactivator for VDR-mediated transcription (Sutton, A. L.,
      Zhang, X., Ellison, T. I., and MacDonald, P. N. (2005) Mol. Endocrinol. 19, 2234
      2244). However, the functional significance of MN1 in osteoblastic cell biology
      is largely unknown. Here, we demonstrate that MN1 expression is increased
      dramatically during differentiation of primary osteoblastic cells. Using
      calvarial osteoblasts derived from wild-type and MN1 knock-out mice, we provide
      data supporting an essential role of MN1 in maintaining appropriate osteoblast
      proliferation, differentiation, and function. MN1 knock-out osteoblasts displayed
      altered morphology, decreased growth rate, impaired motility, and attenuated
      1,25(OH)(2)D(3)/VDR-mediated transcription as well as reduced alkaline
      phosphatase activity and mineralized nodule formation. MN1 null osteoblasts were
      also impaired in supporting osteoclastogenesis in co-culture studies presumably
      because of marked reduction in the RANKL:OPG ratio in the MN1 null cells.
      Mechanistic studies supported a transcriptional role for MN1 in controlling RANKL
      gene expression through activation of the RANKL promoter. Cumulatively, these
      studies indicate an important role for MN1 in maintaining the appropriate
      maturation and function of calvarial osteoblasts.

PMID- 19386591
TI  - ATP regulation of type-1 inositol 1,4,5-trisphosphate receptor activity does not
      require walker A-type ATP-binding motifs.
AB  - ATP is known to increase the activity of the type-1 inositol 1,4,5-trisphosphate
      receptor (InsP3R1). This effect is attributed to the binding of ATP to glycine
      rich Walker A-type motifs present in the regulatory domain of the receptor. Only
      two such motifs are present in neuronal S2+ splice variant of InsP3R1 and are
      designated the ATPA and ATPB sites. The ATPA site is unique to InsP3R1, and the
      ATPB site is conserved among all three InsP3R isoforms. Despite the fact that
      both the ATPA and ATPB sites are known to bind ATP, the relative contribution of
      these two sites to the enhancing effects of ATP on InsP3R1 function is not known.
      We report here a mutational analysis of the ATPA and ATPB sites and conclude
      neither of these sites is required for ATP modulation of InsP3R1. ATP augmented
      InsP3-induced Ca2+ release from permeabilized cells expressing wild type and ATP
      binding site-deficient InsP3R1. Similarly, ATP increased the single channel open
      probability of the mutated InsP3R1 to the same extent as wild type. ATP likely
      exerts its effects on InsP3R1 channel function via a novel and as yet
      unidentified mechanism.

PMID- 19386592
TI  - Decreased expression of cholesterol 7alpha-hydroxylase and altered bile acid
      metabolism in Apobec-1-/- mice lead to increased gallstone susceptibility.
AB  - Quantitative trait mapping in mice identified a susceptibility locus for
      gallstones (Lith6) spanning the Apobec-1 locus, the structural gene encoding the
      RNA-specific cytidine deaminase responsible for production of apolipoprotein B48
      in mammalian small intestine and rodent liver. This observation prompted us to
      compare dietary gallstone susceptibility in Apobec-1(-/-) mice and congenic
      C57BL/6 wild type controls. When fed a lithogenic diet (LD) for 2 weeks, 90%
      Apobec-1(-/-) mice developed solid gallstones in comparison with 16% wild type
      controls. LD-fed Apobec-1(-/-) mice demonstrated increased biliary cholesterol
      secretion as well as increased cholesterol saturation and bile acid
      hydrophobicity indices. These changes occurred despite a relative decrease in
      cholesterol absorption in LD-fed Apobec-1(-/-) mice. Among the possible
      mechanisms to account for this phenotype, expression of Cyp7a1 mRNA and protein
      were significantly decreased in chow-fed Apobec-1(-/-) mice, decreasing further
      in LD-fed animals. Cyp7a1 transcription in hepatocyte nuclei, however, was
      unchanged in Apobec-1(-/-) mice, excluding transcriptional repression as a
      potential mechanism for decreased Cyp7a1 expression. We demonstrated that APOBEC
      1 binds to AU-rich regions of the 3'-untranslated region of the Cyp7a1
      transcript, containing the UUUN(A/U)U consensus motif, using both UV cross
      linking to recombinant APOBEC-1 and in vivo RNA co-immunoprecipitation. In vivo
      Apobec-1-dependent modulation of Cyp7a1 expression was further confirmed
      following adenovirus-Apobec-1 administration to chow-fed Apobec-1(-/-) mice,
      which rescued Cyp7a1 gene expression. Taken together, the findings suggest that
      the AU-rich RNA binding-protein Apobec-1 mediates post-transcriptional regulation
      of murine Cyp7a1 expression and influences susceptibility to diet-induced
      gallstone formation.

PMID- 19386593
TI  - The action of 11-cis-retinol on cone opsins and intact cone photoreceptors.
AB  - 11-cis-retinol has previously been shown in physiological experiments to promote
      dark adaptation and recovery of photoresponsiveness of bleached salamander red
      cones but not of bleached salamander red rods. The purpose of this study was to
      evaluate the direct interaction of 11-cis-retinol with expressed human and
      salamander cone opsins, and to determine by microspectrophotometry pigment
      formation in isolated salamander photoreceptors. We show here in a cell-free
      system using incorporation of radioactive guanosine 5'-3-O-(thio)triphosphate
      into transducin as an index of activity, that 11-cis-retinol inactivates
      expressed salamander cone opsins, acting an inverse agonist. Similar results were
      obtained with expressed human red and green opsins. 11-cis-retinol had no
      significant effect on the activity of human blue cone opsin. In contrast, 11-cis
      retinol activates the expressed salamander and human red rod opsins, acting as an
      agonist. Using microspectrophotometry of salamander cone photoreceptors before
      and after bleaching and following subsequent treatment with 11-cis-retinol, we
      show that 11-cis-retinol promotes pigment formation. Pigment was not formed in
      salamander red rods or green rods (containing the same opsin as blue cones)
      treated under the same conditions. These results demonstrate that 11-cis-retinol
      is not a useful substrate for rod photoreceptors although it is for cone
      photoreceptors. These data support the premise that rods and cones have
      mechanisms for handling retinoids and regenerating visual pigment that are
      specific to photoreceptor type. These mechanisms are critical to providing
      regenerated pigments in a time scale required for the function of these two types
      of photoreceptors.

PMID- 19386594
TI  - Herpes simplex virus gD forms distinct complexes with fusion executors gB and
      gH/gL in part through the C-terminal profusion domain.
AB  - Herpes simplex virus entry into cells requires a multipartite fusion apparatus
      made of glycoprotein D (gD), gB, and heterodimer gH/gL. gD serves as a receptor
      binding glycoprotein and trigger of fusion; its ectodomain is organized in an N
      terminal domain carrying the receptor-binding sites and a C-terminal domain
      carrying the profusion domain, required for fusion but not receptor binding. gB
      and gH/gL execute fusion. To understand how the four glycoproteins cross-talk to
      each other, we searched for biochemical defined complexes in infected and
      transfected cells and in virions. Previously, interactions were detected in
      transfected whole cells by split green fluorescent protein complementation
      (Atanasiu, D., Whitbeck, J. C., Cairns, T. M., Reilly, B., Cohen, G. H., and
      Eisenberg, R. J. (2007) Proc. Natl. Acad. Sci. U. S. A. 104, 18718-18723;
      Avitabile, E., Forghieri, C., and Campadelli-Fiume, G. (2007) J. Virol. 81, 11532
      11537); it was not determined whether they led to biochemical complexes. Infected
      cells harbor a gD-gH complex (Perez-Romero, P., Perez, A., Capul, A., Montgomery,
      R., and Fuller, A. O. (2005) J. Virol. 79, 4540-4544). We report that gD formed
      complexes with gB in the absence of gH/gL and with gH/gL in the absence of gB.
      Complexes with similar composition were formed in infected and transfected cells.
      They were also present in virions prior to entry and did not increase at virus
      entry into the cell. A panel of gD mutants enabled the preliminary location of
      part of the binding site in gD to gB to the amino acids 240-260 portion and
      downstream with Thr304-Pro305 as critical residues and of the binding site to
      gH/gL at the amino acids 260-310 portion with Pro291-Pro292 as critical residues.
      The results indicate that gD carries composite-independent binding sites for gB
      and gH/gL, both of which are partly located in the profusion domain.

PMID- 19386595
TI  - The lupane-type triterpene 30-oxo-calenduladiol is a CCR5 antagonist with anti
      HIV-1 and anti-chemotactic activities.
AB  - The existence of drug-resistant human immunodeficiency virus (HIV) viruses in
      patients receiving antiretroviral treatment urgently requires the
      characterization and development of new antiretroviral drugs designed to inhibit
      resistant viruses and to complement the existing antiretroviral strategies
      against AIDS. We assayed several natural or semi-synthetic lupane-type
      pentacyclic triterpenes in their ability to inhibit HIV-1 infection in permissive
      cells. We observed that the 30-oxo-calenduladiol triterpene, compound 1,
      specifically impaired R5-tropic HIV-1 envelope-mediated viral infection and cell
      fusion in permissive cells, without affecting X4-tropic virus. This lupane
      derivative competed for the binding of a specific anti-CCR5 monoclonal antibody
      or the natural CCL5 chemokine to the CCR5 viral coreceptor with high affinity. 30
      oxo-calenduladiol seems not to interact with the CD4 antigen, the main HIV
      receptor, or the CXCR4 viral coreceptor. Our results suggest that compound 1 is a
      specific CCR5 antagonist, because it binds to the CCR5 receptor without
      triggering cell signaling or receptor internalization, and inhibits RANTES
      (regulated on activation normal T cell expressed and secreted)-mediated CCR5
      internalization, intracellular calcium mobilization, and cell chemotaxis.
      Furthermore, compound 1 appeared not to interact with beta-chemokine receptors
      CCR1, CCR2b, CCR3, or CCR4. Thereby, the 30-oxo-calenduladiol-associated anti-HIV
      1 activity against R5-tropic virus appears to rely on the selective occupancy of
      the CCR5 receptor to inhibit CCR5-mediated HIV-1 infection. Therefore, it is
      plausible that the chemical structure of 30-oxo-calenduladiol or other related
      dihydroxylated lupane-type triterpenes could represent a good model to develop
      more potent anti-HIV-1 molecules to inhibit viral infection by interfering with
      early fusion and entry steps in the HIV life cycle.

PMID- 19386596
TI  - The superagonistic activity of bovine thyroid-stimulating hormone (TSH) and the
      human TR1401 TSH analog is determined by specific amino acids in the hinge region
      of the human TSH receptor.
AB  - Bovine TSH (bTSH) has a higher affinity to the human TSHR (hTSHR) and a higher
      signaling activity than human TSH (hTSH). The molecular reasons for these
      phenomena are unknown. Distinct negatively charged residues (Glu297, Glu303, and
      Asp382) in the hinge region of the hTSHR are known to be important for bTSH
      binding and signaling. To investigate the potential relevance of these positions
      for differences between bTSH and hTSH in the interaction to the hTSHR, we
      determined bTSH- and hTSH-mediated cAMP production of several substitutions at
      these three hinge residues. To examine specific variations of hTSH, we also
      investigated the superagonistic hTSH analog TR1401 (TR1401), whose sequence
      differs from hTSH by four additional positively charged amino acids that are also
      present in bTSH. To characterize possible interactions between the acidic hTSHR
      positions Glu297, Glu303, or Asp382 and the additional basic residues of TR1401,
      we investigated TR1401 binding and signaling properties. Our data reveal
      increased cAMP signaling of the hTSHR using TR1401 and bTSH compared with hTSH.
      Whereas Asp382 seems to be important for bTSH- and TR1401-mediated but not for
      hTSH-mediated signaling, the substitution E297K exhibits a decreased signaling
      for all three TSH variants. Interestingly, bTSH and TR1401 showed only a slightly
      different binding pattern. These observations imply that specific residues of the
      hinge region are mediators of the superagonistic activity of bTSH and TR1401 in
      contrast to hTSH. Moreover, the simultaneous localization of binding components
      in the glycoprotein hormone molecule and the receptor hinge region permits
      important reevaluation of interacting hormone receptor domains.

PMID- 19386598
TI  - Differential regulation of actin polymerization and structure by yeast formin
      isoforms.
AB  - The budding yeast formins, Bnr1 and Bni1, behave very differently with respect to
      their interactions with muscle actin. However, the mechanisms underlying these
      differences are unclear, and these formins do not interact with muscle actin in
      vivo. We use yeast wild type and mutant actins to further assess these
      differences between Bnr1 and Bni1. Low ionic strength G-buffer does not promote
      actin polymerization. However, Bnr1, but not Bni1, causes the polymerization of
      pyrene-labeled Mg-G-actin in G-buffer into single filaments based on fluorometric
      and EM observations. Polymerization by Bnr1 does not occur with Ca-G-actin. By
      cosedimentation, maximum filament formation occurs at a Bnr1:actin ratio of 1:2.
      The interaction of Bnr1 with pyrene-labeled S265C Mg-actin yields a pyrene
      excimer peak, from the cross-strand interaction of pyrene probes, which only
      occurs in the context of F-actin. In F-buffer, Bnr1 promotes much faster yeast
      actin polymerization than Bni1. It also bundles the F-actin in contrast to the
      low ionic strength situation where only single filaments form. Thus, the
      differences previously observed with muscle actin are not actin isoform-specific.
      The binding of both formins to F-actin saturate at an equimolar ratio, but only
      about 30% of each formin cosediments with F-actin. Finally, addition of Bnr1 but
      not Bni1 to pyrene-labeled wild type and S265C Mg-F actins enhanced the pyrene-
      and pyrene-excimer fluorescence, respectively, suggesting Bnr1 also alters F
      actin structure. These differences may facilitate the ability of Bnr1 to form the
      actin cables needed for polarized delivery of nutrients and organelles to the
      growing yeast bud.

PMID- 19386597
TI  - Plasma membrane-associated annexin A6 reduces Ca2+ entry by stabilizing the
      cortical actin cytoskeleton.
AB  - The annexins are a family of Ca(2+)- and phospholipid-binding proteins, which
      interact with membranes upon increase of [Ca(2+)](i) or during cytoplasmic
      acidification. The transient nature of the membrane binding of annexins
      complicates the study of their influence on intracellular processes. To address
      the function of annexins at the plasma membrane (PM), we fused fluorescent
      protein-tagged annexins A6, A1, and A2 with H- and K-Ras membrane anchors. Stable
      PM localization of membrane-anchored annexin A6 significantly decreased the store
      operated Ca(2+) entry (SOCE), but did not influence the rates of Ca(2+)
      extrusion. This attenuation was specific for annexin A6 because PM-anchored
      annexins A1 and A2 did not alter SOCE. Membrane association of annexin A6 was
      necessary for a measurable decrease of SOCE, because cytoplasmic annexin A6 had
      no effect on Ca(2+) entry as long as [Ca(2+)](i) was below the threshold of
      annexin A6-membrane translocation. However, when [Ca(2+)](i) reached the levels
      necessary for the Ca(2+)-dependent PM association of ectopically expressed wild
      type annexin A6, SOCE was also inhibited. Conversely, knockdown of the endogenous
      annexin A6 in HEK293 cells resulted in an elevated Ca(2+) entry. Constitutive PM
      localization of annexin A6 caused a rearrangement and accumulation of F-actin at
      the PM, indicating a stabilized cortical cytoskeleton. Consistent with these
      findings, disruption of the actin cytoskeleton using latrunculin A abolished the
      inhibitory effect of PM-anchored annexin A6 on SOCE. In agreement with the
      inhibitory effect of annexin A6 on SOCE, constitutive PM localization of annexin
      A6 inhibited cell proliferation. Taken together, our results implicate annexin A6
      in the actin-dependent regulation of Ca(2+) entry, with consequences for the
      rates of cell proliferation.

PMID- 19386599
TI  - A novel function of thrombin-activatable fibrinolysis inhibitor during rat liver
      regeneration and in growth-promoted hepatocytes in primary culture.
AB  - Thrombin-activatable fibrinolysis inhibitor (TAFI) exhibits anti-fibrinolytic
      activity by removing C-terminal lysine residues from fibrin or plasminogen
      receptor proteins on the cellular surface, and plays an important role in the
      regulation of fibrinolysis. In this study, we examined the regulation of TAFI in
      hepatocytes during liver regeneration, and revealed its pivotal role in
      hepatocyte proliferation. In rat models, partial hepatectomy or carbon
      tetrachloride (CCl4)-induced acute liver injury suppressed the levels of plasma
      TAFI activity and hepatic TAFI mRNA, whereas this operation markedly increased
      both the hepatic plasmin activity and the level of proliferating cell nuclear
      antigen. In primary cultures of rat hepatocytes, the TAFI mRNA level was
      decreased under growth-promoting culture conditions. Treatment of the hepatocytes
      with TAFI siRNA increased the amount of plasmin on the hepatocytes and promoted
      hepatocyte proliferation. We concluded that TAFI regulates plasmin activity
      through its enzymatic activity whereby it reduces the plasminogen-binding
      capacity of the hepatocytes. The TAFI gene expression is down-regulated in
      hepatocyte proliferation for producing a fibrinolytic microenvironment suitable
      for cell growth. This is the first report on the role of TAFI in the pericellular
      fibrinolysis necessary for cellular proliferation.

PMID- 19386600
TI  - Regulation of platelet-derived growth factor receptor function by integrin
      associated cell surface transglutaminase.
AB  - A functional collaboration between growth factor receptors such as platelet
      derived growth factor receptor (PDGFR) and integrins is required for effective
      signal transduction in response to soluble growth factors. However, the
      mechanisms of synergistic PDGFR/integrin signaling remain poorly understood. Our
      previous work showed that cell surface tissue transglutaminase (tTG) induces
      clustering of integrins and amplifies integrin signaling by acting as an integrin
      binding adhesion co-receptor for fibronectin. Here we report that in fibroblasts
      tTG enhances PDGFR-integrin association by interacting with PDGFR and bridging
      the two receptors on the cell surface. The interaction between tTG and PDGFR
      reduces cellular levels of the receptor by accelerating its turnover. Moreover,
      the association of PDGFR with tTG causes receptor clustering, increases PDGF
      binding, promotes adhesion-mediated and growth factor-induced PDGFR activation,
      and up-regulates downstream signaling. Importantly, tTG is required for efficient
      PDGF-dependent proliferation and migration of fibroblasts. These results reveal a
      previously unrecognized role for cell surface tTG in the regulation of the joint
      PDGFR/integrin signaling and PDGFR-dependent cell responses.

PMID- 19386601
TI  - Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha
      DNA binding with expression profiling of hypoxia-inducible transcripts.
AB  - Hypoxia-inducible factor (HIF) controls an extensive range of adaptive responses
      to hypoxia. To better understand this transcriptional cascade we performed genome
      wide chromatin immunoprecipitation using antibodies to two major HIF-alpha
      subunits, and correlated the results with genome-wide transcript profiling.
      Within a tiled promoter array we identified 546 and 143 sequences that bound,
      respectively, to HIF-1alpha or HIF-2alpha at high stringency. Analysis of these
      sequences confirmed an identical core binding motif for HIF-1alpha and HIF-2alpha
      (RCGTG) but demonstrated that binding to this motif was highly selective, with
      binding enriched at distinct regions both upstream and downstream of the
      transcriptional start. Comparison of HIF-promoter binding data with bidirectional
      HIF-dependent changes in transcript expression indicated that whereas a
      substantial proportion of positive responses (>20% across all significantly
      regulated genes) are direct, HIF-dependent gene suppression is almost entirely
      indirect. Comparison of HIF-1alpha- versus HIF-2alpha-binding sites revealed that
      whereas some loci bound HIF-1alpha in isolation, many bound both isoforms with
      similar affinity. Despite high-affinity binding to multiple promoters, HIF-2alpha
      contributed to few, if any, of the transcriptional responses to acute hypoxia at
      these loci. Given emerging evidence for biologically distinct functions of HIF
      1alpha versus HIF-2alpha understanding the mechanisms restricting HIF-2alpha
      activity will be of interest.

PMID- 19386602
TI  - Interleukin-32 expression in the pancreas.
AB  - Interleukin (IL)-32 is a recently described proinflammatory cytokine
      characterized by the induction of nuclear factor (NF)-kappaB activation. We
      studied IL-32 expression in human pancreatic tissue and pancreatic cancer cell
      lines. Tissue samples were obtained surgically. IL-32 expression was evaluated by
      standard immunohistochemical procedures. IL-32 mRNA expression was analyzed by
      Northern blotting and real time PCR analyses. IL-32 was weakly immunoexpressed by
      pancreatic duct cells. In the inflamed lesions of chronic pancreas, the ductal
      expression of IL-32 was markedly increased. A strong expression of IL-32alpha was
      detected in the pancreatic cancer cells. In pancreatic cancer cell lines (PANC-1,
      MIA PaCa-2, and BxPC-3 cells), the expression of IL-32 mRNA and protein was
      enhanced by IL-1beta, interferon (IFN)-gamma, and tumor necrosis factor (TNF)
      alpha. An inhibitor of phosphatidylinositol 3-kinase (LY294002) significantly
      suppressed the IL-1beta-, IFN-gamma- and TNF-alpha-induced IL-32 mRNA expression.
      The blockade of NF-kappaB and activated protein-1 activation markedly suppressed
      the IL-1beta-, IFN-gamma-, and/or TNF-alpha-induced IL-32 mRNA expression.
      Furthermore, IL-32-specific small interfering RNA significantly decreased the
      uptake of [3H]thymidine and increased the annexin V-positive population
      (apoptotic cells) in PANC-1 cells. IL-32 knockdown also suppressed the mRNA
      expression of antiapoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1). Pancreatic duct
      cells are the local source of IL-32, and IL-32 may play an important role in
      inflammatory responses and pancreatic cancer growth.

PMID- 19386603
TI  - ATP-mediated activation of the NADPH oxidase DUOX1 mediates airway epithelial
      responses to bacterial stimuli.
AB  - Activation of the NADPH oxidase homolog dual oxidase 1 (DUOX1) within the airway
      epithelium represents a key mechanism of innate airway host defense, through
      enhanced production of H2O2, which mediates cellular signaling pathways that
      regulate the production of various inflammatory mediators. Production of the CXC
      chemokine interleukin (IL)-8/CXCL8 forms a common epithelial response to many
      diverse stimuli, including bacterial and viral triggers, environmental oxidants,
      and other biological mediators, suggesting the potential involvement of a common
      signaling pathway that may involve DUOX1-dependent H2O2 production. Following
      previous reports showing that DUOX1 is activated by extracellular ATP and
      purinergic receptor stimulation, this study demonstrates that airway epithelial
      IL-8 production in response to several bacterial stimuli involves ATP release and
      DUOX1 activation. ATP-mediated DUOX1 activation resulted in the activation of
      ERK1/2 and NF-kappaB pathways, which was associated with epidermal growth factor
      receptor (EGFR) ligand shedding by ADAM17 (a disintegrin and metalloproteinase
      17). Although ATP-mediated ADAM17 activation and IL-8 release were not prevented
      by extracellular H2O2 scavenging by catalase, these responses were attenuated by
      intracellular scavengers of H2O2 or related oxidants, suggesting an intracellular
      redox signaling mechanism. Both ADAM17 activation and IL-8 release were
      suppressed by inhibitors of EGFR/ERK1/2 signaling, which can regulate ADAM17
      activity by serine/threonine phosphorylation. Collectively, our results indicate
      that ATP-mediated DUOX1 activation represents a common response mechanism to
      several environmental stimuli, involving H2O2-dependent EGFR/ERK activation,
      ADAM17 activation, and EGFR ligand shedding, leading to amplified epithelial EGFR
      activation and IL-8 production.

PMID- 19386604
TI  - Oxidative stress renders retinal pigment epithelial cells susceptible to
      complement-mediated injury.
AB  - Uncontrolled activation of the alternative pathway of complement is thought to be
      associated with age-related macular degeneration (AMD). The alternative pathway
      is continuously activated in the fluid phase, and tissue surfaces require
      continuous complement inhibition to prevent spontaneous autologous tissue injury.
      Here, we examined the effects of oxidative stress on the ability of immortalized
      human retinal pigment epithelial cells (ARPE-19) to regulate complement
      activation on their cell surface. Combined treatment with H(2)O(2) (to induce
      oxidative stress) and complement-sufficient serum was found to disrupt the
      barrier function of stable ARPE-19 monolayers as determined by transepithelial
      resistance (TER) measurements. Neither treatment alone had any effect. TER
      reduction was correlated with increased cell surface deposition of C3, and could
      be prevented by using C7-depleted serum, an essential component of the terminal
      complement pathway. Treatment with H(2)O(2) reduced surface expression of the
      complement inhibitors DAF, CD55, and CD59, and impaired regulation at the cell
      surface by factor H present within the serum. Combined treatment of the
      monolayers with H(2)O(2) and serum elicited polarized secretion of vascular
      epidermal growth factor (VEGF). Both, secretion of VEGF and TER reduction could
      be attenuated using either an alternative pathway inhibitor or by blocking VEGF
      receptor-1/2 signaling. Regarded together, these studies demonstrate that
      oxidative stress reduces regulation of complement on the surface of ARPE-19
      cells, increasing complement activation. This sublytic activation results in VEGF
      release, which mediates disruption of the cell monolayer. These findings link
      oxidative stress, complement activation, and apical VEGF release, which have all
      been associated with the pathogenesis of AMD.

PMID- 19386605
TI  - The major role of the Rab Ypt7p in vacuole fusion is supporting HOPS membrane
      association.
AB  - Yeast vacuole fusion requires soluble N-ethylmaleimide-sensitive factor
      attachment protein receptors (SNAREs), the Rab GTPase Ypt7p, vacuolar lipids,
      Sec17p and Sec18p, and the homotypic fusion and vacuole protein sorting complex
      (HOPS). HOPS is a multisubunit protein with direct affinities for SNAREs,
      vacuolar lipids, and the GTP-bound form of Ypt7p; each of these affinities
      contributes to HOPS association with the organelle. Using all-purified
      components, we have reconstituted fusion, but the Rab Ypt7p was not required. We
      now report that phosphorylation of HOPS by the vacuolar kinase Yck3p blocks HOPS
      binding to vacuolar lipids, making HOPS membrane association and the ensuing
      fusion depend on the presence of Ypt7p. In accord with this finding in the
      reconstituted fusion reaction, the inactivation of Ypt7p by the GTPase-activating
      protein Gyp1-46p only blocks the fusion of purified vacuoles when Yck3p is
      present and active. Thus, although Ypt7p may contribute to other fusion
      functions, its central role is to bind HOPS to the membrane.

PMID- 19386606
TI  - In vivo selection of kinase-responsive RNA elements controlling alternative
      splicing.
AB  - Alternative pre-mRNA splicing is often controlled by cell signals, for example,
      those activating the cAMP-dependent protein kinase (PKA) or the Ca2+/calmodulin
      dependent protein kinase IV (CaMKIV). We have shown that CaMKIV regulates
      alternative splicing through short CA repeats and hnRNP L. Here we use a splicing
      reporter that shows PKA/CaMKIV promotion of exon inclusion to select from exons
      containing random 13-nt sequences for RNA elements responsive to the kinases in
      cultured cells. This selection not only identified both PKA- and CaMKIV
      responsive elements that are similar to the CaMKIV-responsive RNA element 1
      (CaRRE1) or CA repeats, but also A-rich elements not previously known to respond
      to these kinases. Consistently, hnRNP L is identified as a factor binding the CA
      rich elements. Analyses of the motifs in the highly responsive elements indicate
      that they are indeed critical for the kinase effect and are enriched in
      alternative exons. Interestingly, a CAAAAAA motif is sufficient for the
      PKA/CaMKIV-regulated splicing of the exon 16 of the CaMK kinase beta1 (CaMKK2)
      transcripts, implying a role of this motif in signaling cross-talk or feedback
      regulation between these kinases through alternative splicing. Therefore, these
      experiments identified a group of RNA elements responsive to PKA and CaMKIV from
      in vivo selection. This also provides an approach for selecting RNA elements
      similarly responsive to other cell signals controlling alternative splicing.

PMID- 19386607
TI  - Tubacin kills Epstein-Barr virus (EBV)-Burkitt lymphoma cells by inducing
      reactive oxygen species and EBV lymphoblastoid cells by inducing apoptosis.
AB  - Tubacin is a small molecule inhibitor of histone deacetylase 6 and blocks
      aggresome activity. We found that Epstein-Barr virus (EBV)-positive Burkitt
      lymphoma (BL) cells were generally killed by lower doses of tubacin than EBV
      transformed lymphoblastoid cells (LCLs) or EBV-negative BL cells. Tubacin induced
      apoptosis of LCLs, which was inhibited by pretreatment with a pancaspase
      inhibitor but not by butylated hydroxyanisole, which inhibits reactive oxygen
      species. In contrast, tubacin killed EBV-positive BL cells in a caspase-3
      independent pathway that involved reactive oxygen species and was blocked by
      butylated hydroxyanisole. Previously, we showed that bortezomib, a proteasome
      inhibitor, induces apoptosis of EBV LCLs and that LCLs are killed by lower doses
      of bortezomib than EBV-positive BL cells. Here we found that the combination of
      bortezomib and tubacin acted in synergy to kill EBV-positive BL cells and LCLs.
      Tubacin or the combination of bortezomib and tubacin did not induce EBV lytic
      replication. These findings suggest that the combination of a proteasome
      inhibitor and an HDAC6 inhibitor may represent a useful strategy for the
      treatment of certain EBV-associated B cell lymphomas.

PMID- 19386608
TI  - Identification and characterization of a novel lysophosphatidic acid receptor,
      p2y5/LPA6.
AB  - p2y5 is an orphan G protein-coupled receptor that is closely related to the
      fourth lysophosphatidic acid (LPA) receptor, LPA4. Here we report that p2y5 is a
      novel LPA receptor coupling to the G13-Rho signaling pathway. "LPA receptor-null"
      RH7777 and B103 cells exogenously expressing p2y5 showed [3H]LPA binding, LPA
      induced [35S]guanosine 5'-3-O-(thio)triphosphate binding, Rho-dependent
      alternation of cellular morphology, and Gs/13 chimeric protein-mediated cAMP
      accumulation. LPA-induced contraction of human umbilical vein endothelial cells
      was suppressed by small interfering RNA knockdown of endogenously expressed p2y5.
      We also found that 2-acyl-LPA had higher activity to p2y5 than 1-acyl-LPA. A
      recent study has suggested that p2y5 is an LPA receptor essential for human hair
      growth. We confirmed that p2y5 is a functional LPA receptor and propose to
      designate this receptor LPA6.

PMID- 19386609
TI  - Low-dose terlipressin plus banding ligation versus low-dose terlipressin alone in
      the prevention of very early rebleeding of oesophageal varices.
AB  - BACKGROUND: Very early rebleeding is frequently encountered in patients with
      acute oesophageal variceal bleeding. A trial was designed to assess the efficacy
      and safety in patients with no active bleeding at endoscopy, receiving banding
      ligation association with terlipressin to prevent very early rebleeding. METHODS:
      Patients with no active variceal bleeding at endoscopy were evaluated. Eligible
      patients were randomised to receive terlipressin infusion alone for 5 days
      (Terlipressin group) or banding ligation plus terlipressin infusion for 2 days
      (Combined group). Primary endpoints were treatment failure and very early
      rebleeding. RESULTS: The terlipressin group was composed of 46 patients and the
      Combined group was composed of 47 patients. Both groups were comparable in terms
      of baseline data. Forty-eight-hour haemostasis was achieved in 91% in the
      Terlipressin group and 98% in the Combined group (p = 0.20). Very early
      rebleeding within 48-120 h occurred in 7 patients (15%) in the Terlipressin group
      but not in any patients (0%) in the Combined group (p = 0.006). Treatment failure
      was 24% in the Terlipressin group and 2% in the Combined group (p = 0.002).
      Multivariate analysis revealed that treatment (OR 0.081; 95% CI 0.010 to 0.627)
      was the only predictive factor of very early rebleeding. Blood requirement was
      significantly lower in the Combined group than in the Terlipressin group.
      Complications and 6-week survival were similar in both groups. CONCLUSIONS:
      Combination of banding ligation and terlipressin infusion for 2 days was superior
      to only infusion of terlipressin for 5 days in the reduction of very early
      rebleeding and treatment failure in patients with inactive variceal bleeding at
      endoscopy. TRIAL REGISTRATION NUMBER: ISRCTN28353453.

PMID- 19386610
TI  - Bone loss in patients with active early rheumatoid arthritis: infliximab and
      methotrexate compared with methotrexate treatment alone. Explorative analysis
      from a 12-month randomised, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To examine the effect of infliximab plus methotrexate (MTX) compared
      with placebo plus MTX on bone loss in patients with early rheumatoid arthritis
      (RA) in a double-blind randomised study design. Further, to explore the
      associations between bone loss and markers of RA disease. METHODS: All 20
      patients with RA (10 patients in each treatment group) had active, early RA. Bone
      mineral density (BMD) was assessed at the hand, lumbar spine (L2-4) and hip by
      dual energy x-ray absorptiometry at baseline and 12 months' follow-up. Clinical
      data were collected at regular visits. RESULTS: BMD loss was significantly
      reduced in the infliximab group compared with the placebo group at the femoral
      neck (-0.35% vs -3.43%, p = 0.01) and total hip (-0.23% vs -2.62%, p = 0.03) but
      not at the hand (-2.09% vs -2.82%, p = 0.82) and spine (-0.75% vs -1.77%, p =
      0.71). Measures of disease process and joint damage were found to be
      independently associated with bone loss. CONCLUSIONS: This study provides strong
      evidence of a causal link between inflammation and bone loss in RA. The anti
      inflammatory effect of infliximab was potent enough to arrest inflammatory bone
      loss at the hip but not at the spine and hand.

PMID- 19386611
TI  - Culture, risk factors and mortality: can Switzerland add missing pieces to the
      European puzzle?
AB  - BACKGROUND: The aim was to compare cause-specific mortality, self-rated health
      (SRH) and risk factors in the French and German part of Switzerland and to
      discuss to what extent variations between these regions reflect differences
      between France and Germany. METHODS: Data were used from the general population
      of German and French Switzerland with 2.8 million individuals aged 45-74 years,
      contributing 176 782 deaths between 1990 and 2000. Adjusted mortality risks were
      calculated from the Swiss National Cohort, a longitudinal census-based record
      linkage study. Results were contrasted with cross-sectional analyses of SRH and
      risk factors (Swiss Health Survey 1992/3) and with cross-sectional national and
      international mortality rates for 1980, 1990 and 2000. RESULTS: Despite similar
      all-cause mortality, there were substantial differences in cause-specific
      mortality between Swiss regions. Deaths from circulatory disease were more common
      in German Switzerland, while causes related to alcohol consumption were more
      prevalent in French Switzerland. Many but not all of the mortality differences
      between the two regions could be explained by variations in risk factors. Similar
      patterns were found between Germany and France. CONCLUSION: Characteristic
      mortality and behavioural differentials between the German- and the French
      speaking parts of Switzerland could also be found between Germany and France.
      However, some of the international variations in mortality were not in line with
      the Swiss regional comparison nor with differences in risk factors. These could
      relate to peculiarities in assignment of cause of death. With its cultural
      diversity, Switzerland offers the opportunity to examine cultural determinants of
      mortality without bias due to different statistical systems or national health
      policies.

PMID- 19386612
TI  - Low-income groups and behaviour change interventions: a review of intervention
      content, effectiveness and theoretical frameworks.
AB  - BACKGROUND: Interventions to change health-related behaviours have potential to
      increase health inequalities. METHODS: This review investigated the effectiveness
      of interventions targeting low-income groups to reduce smoking or increase
      physical activity and/or healthy eating. Of 9766 papers identified by the search
      strategy, 13 met the inclusion criteria. Intervention content was coded into
      component technique and theoretical basis, and examined as a potential source of
      effect heterogeneity. RESULTS: Interventions were heterogeneous, comprising 4-19
      techniques. Nine interventions had positive effects, seven resulted in no change
      and one had an adverse effect. Effective interventions had a tendency to have
      fewer techniques than ineffective interventions, with no evidence for any
      technique being generally effective or ineffective. Only six studies cited theory
      relative to intervention development, with little information about how theory
      was used and no obvious association with intervention content or effect.
      CONCLUSION: This review shows that behaviour change interventions, particularly
      those with fewer techniques, can be effective in low-income groups, but
      highlights the lack of evidence to draw on in informing the design of
      interventions for disadvantaged groups.

PMID- 19386613
TI  - Root secretions: from genes and molecules to microbial associations.

PMID- 19386614
TI  - Wheat.
AB  - Wheat is the dominant crop in temperate countries being used for human food and
      livestock feed. Its success depends partly on its adaptability and high yield
      potential but also on the gluten protein fraction which confers the viscoelastic
      properties that allow dough to be processed into bread, pasta, noodles, and other
      food products. Wheat also contributes essential amino acids, minerals, and
      vitamins, and beneficial phytochemicals and dietary fibre components to the human
      diet, and these are particularly enriched in whole-grain products. However, wheat
      products are also known or suggested to be responsible for a number of adverse
      reactions in humans, including intolerances (notably coeliac disease) and
      allergies (respiratory and food). Current and future concerns include sustaining
      wheat production and quality with reduced inputs of agrochemicals and developing
      lines with enhanced quality for specific end-uses, notably for biofuels and human
      nutrition.

PMID- 19386615
TI  - Water movement into dormant and non-dormant wheat (Triticum aestivum L.) grains.
AB  - The movement of water into harvest-ripe grains of dormant and non-dormant
      genotypes of wheat (Triticum aestivum L.) was investigated using Magnetic
      Resonance Micro-Imaging (MRMI). Images of virtual sections, both longitudinal and
      transverse, throughout the grain were collected at intervals after the start of
      imbibition and used to reconstruct a picture of water location within the
      different grain tissues and changes over time. The observations were supplemented
      by the weighing measurements of water content and imbibition of grains in water
      containing I(2)/KI which stains starch and lipid, thereby acting as a marker for
      water. In closely related genotypes, with either a dormant or a non-dormant
      phenotype, neither the rate of increase in water content nor the pattern of water
      distribution within the grain was significantly different until 18 h, when
      germination became apparent in the non-dormant genotype. Water entered the embryo
      and scutellum during the very early stages of imbibition through the micropyle
      and by 2 h water was clearly evident in the micropyle channel. After 12 h of
      imbibition, embryo structures such as the coleoptile and radicle were clearly
      distinguished. Although water accumulated between the inner (seed coat) and outer
      (pericarp) layers of the coat surrounding the grain, there was no evidence for
      movement of water directly across the coat and into the underlying starchy
      endosperm.

PMID- 19386616
TI  - Seasonal pattern of apoplastic solute accumulation and loss of cell turgor during
      ripening of Vitis vinifera fruit under field conditions.
AB  - Using a novel pressure membrane (PM) apparatus for the extraction of apoplastic
      fluid from field-grown grape (Vitis vinifera L.) berries, our hypothesis that
      significant apoplast solutes accumulate at the beginning of the ripening process
      (i.e. veraison), and that this accumulation might contribute to progressive berry
      softening due to a progressive loss of mesocarp cell turgor pressure (P) was
      tested. It was necessary to correct the solute potential (Psi(s)) of fluid
      collected with the PM for dilution due to the presence of a dead volume in the
      apparatus, but after correction, the Psi(s) obtained with the PM agreed with that
      obtained by low speed centrifugation. A clear decline in fruit apoplastic solute
      potential (psi(S)(A)) began approximately 10 d prior to fruit coloration, and it
      was found to be coincident with a decline in mesocarp cell P and fruit elasticity
      (E). By late in fruit development when berry growth ceased (90 d after anthesis),
      both apoplast and fruit Psi(s) reached almost -4 MPa. These results support the
      hypothesis that a decrease in psi(S)(A) is responsible for the observed loss in
      mesocarp cell P, and is the mechanistic cause of berry softening.

PMID- 19386617
TI  - Head-up tilt induced syncope and adenosine A2A receptor gene polymorphism.
AB  - AIMS: High adenosine plasma levels and high expression of adenosine A(2A)
      receptors are observed in patients with unexplained syncope and a positive head
      up tilt test (HUT). This study aimed to evaluate the single nucleotide
      polymorphism (SNP) (c.1364 T>C) which is the most commonly found polymorphism in
      the A(2A) receptor gene, in patients with unexplained syncope undergoing HUT.
      METHODS AND RESULTS: One hundred and five patients with unexplained syncope who
      underwent HUT were included. Fifty-two had a positive test. Receptor genotype
      determinations were performed in patients and in 121 healthy subjects. Genotype
      (TT, CC, TC) was determined from DNA leucocytes. The distribution of the
      polymorphism showed significant (P < 0.0001) difference when the results of HUT
      were analysed. Fifty-two per cent of patients with a positive HUT had a CC
      genotype and 34.6% a TC genotype, whereas 13.2% of the patients with a negative
      HUT had a CC genotype and 71.7% a TC genotype. Patients with a CC genotype had a
      higher incidence of spontaneous syncopal episodes. CONCLUSION: In patients with
      unexplained syncope, a significant association between high incidence of syncopal
      episodes, positive HUT, and the presence of the CC variant in the adenosine A(2A)
      receptor gene was elicited.

PMID- 19386618
TI  - Oligonucleotides suppress PKB/Akt and act as superinductors of apoptosis in human
      keratinocytes.
AB  - DNA oligonucleotides (ODN) applied to an organism are known to modulate the
      innate and adaptive immune system. Previous studies showed that a CpG-containing
      ODN (CpG-1-PTO) and interestingly, also a non-CpG-containing ODN (nCpG-5-PTO)
      suppress inflammatory markers in skin. In the present study it was investigated
      whether these molecules also influence cell apoptosis. Here we show that CpG-1
      PTO, nCpG-5-PTO, and also natural DNA suppress the phosphorylation of PKB/Akt in
      a cell-type-specific manner. Interestingly, only epithelial cells of the skin
      (normal human keratinocytes, HaCaT and A-431) show a suppression of PKB/Akt. This
      suppressive effect depends from ODN lengths, sequence and backbone. Moreover, it
      was found that TGF alpha-induced levels of PKB/Akt and EGFR were suppressed by
      the ODN tested. We hypothesize that this suppression might facilitate programmed
      cell death. By testing this hypothesis we found an increase of apoptosis markers
      (caspase 3/7, 8, 9, cytosolic cytochrome c, histone associated DNA fragments,
      apoptotic bodies) when cells were treated with ODN in combination with low doses
      of staurosporin, a well-known pro-apoptotic stimulus. In summary the present data
      demonstrate DNA as a modulator of apoptosis which specifically targets skin
      epithelial cells.

PMID- 19386619
TI  - High-resolution genome-wide cytosine methylation profiling with simultaneous copy
      number analysis and optimization for limited cell numbers.
AB  - Many genome-wide assays involve the generation of a subset (or representation) of
      the genome following restriction enzyme digestion. The use of enzymes sensitive
      to cytosine methylation allows high-throughput analysis of this epigenetic
      regulatory process. We show that the use of a dual-adapter approach allows us to
      generate genomic representations that includes fragments of <200 bp in size,
      previously not possible when using the standard approach of using a single
      adapter. By expanding the representation to smaller fragments using HpaII or
      MspI, we increase the representation by these isoschizomers to more than 1.32
      million loci in the human genome, representing 98.5% of CpG islands and 91.1% of
      refSeq promoters. This advance allows the development of a new, high-resolution
      version of our HpaII-tiny fragment Enrichment by Ligation-mediated PCR (HELP)
      assay to study cytosine methylation. We also show that the MspI representation
      generates information about copy-number variation, that the assay can be used on
      as little as 10 ng of DNA and that massively parallel sequencing can be used as
      an alternative to microarrays to read the output of the assay, making this a
      powerful discovery platform for studies of genomic and epigenomic abnormalities.

PMID- 19386620
TI  - Structural basis for m7G-cap hypermethylation of small nuclear, small nucleolar
      and telomerase RNA by the dimethyltransferase TGS1.
AB  - The 5'-cap of spliceosomal small nuclear RNAs, some small nucleolar RNAs and of
      telomerase RNA was found to be hypermethylated in vivo. The Trimethylguanosine
      Synthase 1 (TGS1) mediates this conversion of the 7-methylguanosine-cap to the
      2,2,7-trimethylguanosine (m(3)G)-cap during maturation of the RNPs. For mammalian
      UsnRNAs the generated m(2,2,7)G-cap is one part of a bipartite import signal
      mediating the transport of the UsnRNP-core complex into the nucleus. In order to
      understand the structural organization of human TGS1 as well as substrate binding
      and recognition we solved the crystal structure of the active TGS1
      methyltransferase domain containing both, the minimal substrate m(7)GTP and the
      reaction product S-adenosyl-L-homocysteine (AdoHcy). The methyltransferase of
      human TGS1 harbors the canonical class 1 methyltransferase fold as well as an
      unique N-terminal, alpha-helical domain of 40 amino acids, which is essential for
      m(7)G-cap binding and catalysis. The crystal structure of the substrate bound
      methyltransferase domain as well as mutagenesis studies provide insight into the
      catalytic mechanism of TGS1.

PMID- 19386621
TI  - MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral
      polarity in epithelial cells.
AB  - MicroRNAs are small noncoding RNA species, some of which are playing important
      roles in cell differentiation. However, the level of participations of microRNAs
      in epithelial cell differentiation is largely unknown. Here, utilizing an
      epithelial differentiation model with T84 cells, we demonstrate that miR-338-3p
      and miR-451 contribute to the formation of epithelial basolateral polarity by
      facilitating translocalization of beta1 integrin to the basolateral membrane.
      Among 250 microRNAs screened in this study, the expression levels of four
      microRNAs (miR-33a, 210, 338-3p and 451) were significantly elevated in the
      differentiated stage of T84 cells, when epithelial cell polarity was established.
      To investigate the involvement of these microRNAs in terms of epithelial cell
      polarity, we executed loss-of- and gain-of-function analyses of these microRNAs.
      The blockade of endogenous miR-338-3p or miR-451 via each microRNA-specific
      antisense oligonucleotides inhibited the translocalization of beta1 integrin to
      the basolateral membrane, whereas inhibition of miR-210 or miR-33a had no effect
      on it. On the other hand, simultaneous transfection of synthetic miR-338-3p and
      miR-451 accelerated the translocalization of beta1 integrin to the basolateral
      membrane, although the introduction of individual synthetic microRNAs exhibited
      no effect. Therefore, we concluded that both miR-338-3p and miR-451 are necessary
      for the development of epithelial cell polarity.

PMID- 19386622
TI  - A genome-wide screen for essential yeast genes that affect telomere length
      maintenance.
AB  - Telomeres are structures composed of repetitive DNA and proteins that protect the
      chromosomal ends in eukaryotic cells from fusion or degradation, thus
      contributing to genomic stability. Although telomere length varies between
      species, in all organisms studied telomere length appears to be controlled by a
      dynamic equilibrium between elongating mechanisms (mainly addition of repeats by
      the enzyme telomerase) and nucleases that shorten the telomeric sequences. Two
      previous studies have analyzed a collection of yeast deletion strains (deleted
      for nonessential genes) and found over 270 genes that affect telomere length
      (Telomere Length Maintenance or TLM genes). Here we complete the list of TLM by
      analyzing a collection of strains carrying hypomorphic alleles of most essential
      genes (DAmP collection). We identify 87 essential genes that affect telomere
      length in yeast. These genes interact with the nonessential TLM genes in a
      significant manner, and provide new insights on the mechanisms involved in
      telomere length maintenance. The newly identified genes span a variety of
      cellular processes, including protein degradation, pre-mRNA splicing and DNA
      replication.

PMID- 19386624
TI  - Predictors of prenatal multivitamin adherence in pregnant women.
AB  - There is no study available that has investigated determinants of prenatal
      multivitamin adherence among pregnant women, based on gastrointestinal (GI)
      adverse events. The objective of this study was to identify determinants
      predicting adherence to prenatal multivitamins in pregnant women who were
      randomized to take 2 different supplements. The authors recruited and interviewed
      70 women on the importance of various factors that may have affected adherence to
      previous and assigned multivitamins. The different factors included GI symptoms
      and swallowing difficulty. The authors used a 5-point scale to measure degree of
      importance. The highest scoring factors for not taking or discontinuing any
      previous multivitamins were fear of or experience of nausea, vomiting, and
      gagging. For women who never took the assigned prenatal multivitamins, the
      highest scoring factors contributing to that decision were fear of nausea, fear
      of vomiting, and health care provider advice. For women who started taking the
      assigned supplements, the most important factors affecting adherence were dosing
      regimen, health care provider advice, and mode of product distribution. Adherence
      to assigned prenatal multivitamins significantly correlated only with the
      importance of constipation in deciding to discontinue any previous multivitamins.
      It is concluded that predictors of adherence to recommended prenatal
      multivitamins during pregnancy are rooted in women's prior experiences with
      multivitamin use.

PMID- 19386623
TI  - Transcriptionally active TFIIH of the early-diverged eukaryote Trypanosoma brucei
      harbors two novel core subunits but not a cyclin-activating kinase complex.
AB  - Trypanosoma brucei is a member of the early-diverged, protistan family
      Trypanosomatidae and a lethal parasite causing African Sleeping Sickness in
      humans. Recent studies revealed that T. brucei harbors extremely divergent
      orthologues of the general transcription factors TBP, TFIIA, TFIIB and TFIIH and
      showed that these factors are essential for initiating RNA polymerase II-mediated
      synthesis of spliced leader (SL) RNA, a trans splicing substrate and key molecule
      in trypanosome mRNA maturation. In yeast and metazoans, TFIIH is composed of a
      core of seven conserved subunits and the ternary cyclin-activating kinase (CAK)
      complex. Conversely, only four TFIIH subunits have been identified in T. brucei.
      Here, we characterize the first protistan TFIIH which was purified in its
      transcriptionally active form from T. brucei extracts. The complex consisted of
      all seven core subunits but lacked the CAK sub-complex; instead it contained two
      trypanosomatid-specific subunits, which were indispensable for parasite viability
      and SL RNA gene transcription. These findings were corroborated by comparing the
      molecular structures of trypanosome and human TFIIH. While the ring-shaped core
      domain was surprisingly congruent between the two structures, trypanosome TFIIH
      lacked the knob-like CAK moiety and exhibited extra densities on either side of
      the ring, presumably due to the specific subunits.

PMID- 19386625
TI  - Mechanism-based enterohepatic circulation model of mycophenolic acid and its
      glucuronide metabolite: assessment of impact of cyclosporine dose in Asian renal
      transplant patients.
AB  - Mycophenolic acid (MPA) is mainly metabolized to MPA-glucuronide (MPAG), which
      may be reconverted to MPA following enterohepatic circulation (EHC). A
      physiologically realistic EHC model was proposed to estimate and assess the
      impact of cyclosporine (CsA) dose on the extent of EHC of MPA and MPAG. After the
      first oral dose of mycophenolate mofetil (MMF), the MPA and MPAG plasma
      concentration-time data of 14 adult renal transplant patients (12 receiving
      concomitant CsA and prednisolone and 2 receiving only concomitant prednisolone
      without CsA) were analyzed by individual pharmacokinetic modeling using a
      proposed 5-compartment drug and metabolite EHC model with a time-varying
      gallbladder emptying process. Simulations were performed to assess the influence
      of the time of bile release after dosing (T(bile)) and the gallbladder emptying
      interval (tau(gall)) on the EHC process. The extent of EHC for both MPA and MPAG
      tended to be lower in the group receiving CsA coadministration and decreased with
      increasing total body weight-adjusted CsA dose. Simulations revealed that T(bile)
      and tau(gall) influenced the time of occurrence and maximum concentration of the
      second peak, as well as the extent of EHC, for MPA and MPAG.

PMID- 19386631
TI  - Human ovarian tissue: vitrification versus conventional freezing.

PMID- 19386626
TI  - Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with
      downregulation of GIP- and GLP-1 receptors and impaired beta-cell function.
AB  - Recent human genetics studies have revealed that common variants of the TCF7L2 (T
      cell factor 7-like 2, formerly known as TCF4) gene are strongly associated with
      type 2 diabetes mellitus (T2DM). We have shown that TCF7L2 expression in the beta
      cells is correlated with function and survival of the insulin-producing
      pancreatic beta-cell. In order to understand how variations in TCF7L2 influence
      diabetes progression, we investigated its mechanism of action in the beta-cell.
      We show robust differences in TCF7L2 expression between healthy controls and
      models of T2DM. While mRNA levels were approximately 2-fold increased in isolated
      islets from the diabetic db/db mouse, the Vancouver Diabetic Fatty (VDF) Zucker
      rat and the high fat/high sucrose diet-treated mouse compared with the non
      diabetic controls, protein levels were decreased. A similar decrease was observed
      in pancreatic sections from patients with T2DM. In parallel, expression of the
      receptors for glucagon-like peptide 1 (GLP-1R) and glucose-dependent
      insulinotropic polypeptide (GIP-R) was decreased in islets from humans with T2DM
      as well as in isolated human islets treated with siRNA to TCF7L2 (siTCF7L2).
      Also, insulin secretion stimulated by glucose, GLP-1 and GIP, but not KCl or
      cyclic adenosine monophosphate (cAMP) was impaired in siTCF7L2-treated isolated
      human islets. Loss of TCF7L2 resulted in decreased GLP-1 and GIP-stimulated AKT
      phosphorylation, and AKT-mediated Foxo-1 phosphorylation and nuclear exclusion.
      Our findings suggest that beta-cell function and survival are regulated through
      an interplay between TCF7L2 and GLP-1R/GIP-R expression and signaling in T2DM.

PMID- 19386632
TI  - Fertility preservation for healthy women: ethical aspects.
AB  - There is currently much debate about cryopreservation of ovarian tissue or
      oocytes as a possible means of fertility preservation for women urgently needing
      potentially sterilizing medical treatment. Although both techniques are still
      experimental, some centres have started offering them also to healthy women who
      want to postpone childbearing until after they may have lost their natural
      reproductive capacity, or fear that they may not before that time find a partner
      with whom to raise a family. This article explores and discusses the ethical
      issues raised by this practice. We argue that there are no convincing a priori
      moral reasons why cryopreservation of ovarian tissue or oocytes should not also
      be available for healthy women. However, this is on the assumption of established
      techniques, also in terms of the efficient and safe use of any frozen reserve.
      The fact that there is still uncertainty about these aspects is rightly seen as a
      reason for only offering cryopreservation of ovarian tissue or oocytes in an
      experimental setting. But does that also mean that these techniques should
      presently only be available for a medical reason, i.e. for women facing
      iatrogenic fertility loss? We argue against this conclusion.

PMID- 19386633
TI  - Analysis of c-fos and zif268 expression reveals time-dependent changes in
      activity inside and outside the lesion projection zone in adult cat area 17 after
      retinal lesions.
AB  - Retinal lesions induce a topographic reorganization in the corresponding lesion
      projection zone (LPZ) in the visual cortex of adult cats. To gain a better
      insight into the reactivation dynamics, we investigated the alterations in
      cortical activity throughout area 17. We implemented in situ hybridization and
      real-time polymerase chain reaction to analyze the spatiotemporal expression
      patterns of the activity marker genes zif268 and c-fos. The immediate early gene
      (IEG) data confirmed a strong and permanent activity decrease in the center of
      the LPZ as previously described by electrophysiology. A recovery of IEG
      expression was clearly measured in the border of the LPZ. We were able to
      register reorganization over 2.5-6 mm. We also present evidence that the central
      retinal lesions concomitantly influence the activity in far peripheral parts of
      area 17. Its IEG expression levels appeared dependent of time and distance from
      the LPZ. We therefore propose that coupled changes in activity occur inside and
      outside the LPZ. In conclusion, alterations in activity reporter gene expression
      throughout area 17 contribute to the lesion-induced functional reorganization.

PMID- 19386634
TI  - Neurovascular congruence during cerebral cortical development.
AB  - There is evidence for interaction between the developing circulatory and nervous
      systems. Blood vessels provide a supporting niche in regions of adult
      neurogenesis. Here we present a systematic analysis of vascular development in
      the embryonic murine cortex and demonstrate that dividing cells, including Tbr2
      positive intermediate progenitor cells, are closer to the vasculature than
      expected from a random distribution. To examine whether neurites of the newly
      generated embryonic neurons find blood vessels as an attractive and permissive
      substrate, we overlayed green fluorescent protein (GFP)-labeled dissociated
      cortical progenitors on embryonic organotypic cortical slice cultures with
      labeled vasculature. Our observations of neurites extending toward and along
      labeled blood vessels support the notion of vascular-neuronal interactions. The
      altered cortical layering had no obvious effect on the vascular patterns within
      the cortical plate (CP) in shaking rat Kawasaki (SRK) and the reeler mutant mouse
      at the ages studied (E19 and P3). It appears that similarly to other neurogenic
      regions in the adult, the embryonic "vascular niche" might influence neural
      progenitor cells during telencephalic neurogenesis, neuronal migration, and
      neurite extension, but the laminar phenotype of cell classes within the CP has
      limited influence on the developing vasculature.

PMID- 19386635
TI  - Integrating visual and tactile information in the perirhinal cortex.
AB  - By virtue of its widespread afferent projections, perirhinal cortex is thought to
      bind polymodal information into abstract object-level representations. Consistent
      with this proposal, deficits in cross-modal integration have been reported after
      perirhinal lesions in nonhuman primates. It is therefore surprising that imaging
      studies of humans have not observed perirhinal activation during visual-tactile
      object matching. Critically, however, these studies did not differentiate between
      congruent and incongruent trials. This is important because successful
      integration can only occur when polymodal information indicates a single object
      (congruent) rather than different objects (incongruent). We scanned
      neurologically intact individuals using functional magnetic resonance imaging
      (fMRI) while they matched shapes. We found higher perirhinal activation
      bilaterally for cross-modal (visual-tactile) than unimodal (visual-visual or
      tactile-tactile) matching, but only when visual and tactile attributes were
      congruent. Our results demonstrate that the human perirhinal cortex is involved
      in cross-modal, visual-tactile, integration and, thus, indicate a functional
      homology between human and monkey perirhinal cortices.

PMID- 19386636
TI  - Quantifying the adequacy of neural representations for a cross-language phonetic
      discrimination task: prediction of individual differences.
AB  - In order for stimuli to be perceptually discriminable, their representations in
      the brain must be distinct. Investigating the task of discriminating the
      syllables /ra/ and /la/, we hypothesized that the more distinct a person's neural
      representations of those sounds were, the better their behavioral ability to
      discriminate them would be. Standard neuroimaging approaches are ill-suited to
      testing this hypothesis as they have problems differentiating between neural
      representations spatially intermingled within the same brain area. We therefore
      performed multi-voxel pattern-based analysis of the functional magnetic resonance
      imaging (fMRI) activity elicited by these syllables, in native speakers of
      English and Japanese. In right primary auditory cortex, the statistical
      separability of these fMRI patterns predicted subjects' behavioral ability to
      tell the sounds apart, not only across groups but also across individuals. This
      opens up a new approach for identifying neural representations and for
      quantifying their task suitability.

PMID- 19386637
TI  - Fragile X mental retardation protein in the driver's seat.

PMID- 19386639
TI  - Qualitative research and Occupational Medicine.

PMID- 19386638
TI  - Dlx1&2 and Mash1 transcription factors control MGE and CGE patterning and
      differentiation through parallel and overlapping pathways.
AB  - Here we define the expression of approximately 100 transcription factors (TFs) in
      progenitors and neurons of the developing mouse medial and caudal ganglionic
      eminences, anlage of the basal ganglia and pallial interneurons. We have begun to
      elucidate the transcriptional hierarchy of these genes with respect to the Dlx
      homeodomain genes, which are essential for differentiation of most gamma
      aminobutyric acidergic projection neurons of the basal ganglia. This analysis
      identified Dlx-dependent and Dlx-independent pathways. The Dlx-independent
      pathway depends in part on the function of the Mash1 basic helix-loop-helix (b
      HLH) TF. These analyses define core transcriptional components that
      differentially specify the identity and differentiation of the globus pallidus,
      basal telencephalon, and pallial interneurons.

PMID- 19386640
TI  - George Clair Tooker, Jr Government Bureau (1956).

PMID- 19386641
TI  - Every cloud has a silver lining ... even a failed private practice.

PMID- 19386643
TI  - Occupational health in Nigeria.

PMID- 19386644
TI  - Lost in translation?

PMID- 19386645
TI  - The role of the science of ergonomics in WRULDs.

PMID- 19386646
TI  - Pitfalls of reviewing reviews.

PMID- 19386647
TI  - Why I became an occupational physician ...

PMID- 19386648
TI  - The Life Events Inventory (LEI).

PMID- 19386649
TI  - Introduction. Putting the 'bio' into bioinformatics.
AB  - Bioinformatic analyses have grown rapidly in sophistication and efficiency to
      accommodate the vast increase in available data. One of the major challenges has
      been to incorporate the growing appreciation of the complexity of molecular
      evolution into new analytical methods. As the reliance on molecular data in
      biology and medicine increases, we need to be confident that these methods
      adequately reflect the underlying processes of genome change. This special issue
      focuses on the way that patterns and processes of molecular evolution are
      influenced by features of populations of whole organisms, such as selection
      pressure, population size and life history. The advantage of this approach to
      molecular evolution is that it views genomic change not simply as a biochemical
      or stochastic process, but as the result of a complex series of interactions that
      shape the kinds of genomic changes that can and do happen.

PMID- 19386650
TI  - On the problems of a closed marriage: celebrating Darwin 200.
AB  - Darwin devoted much of his working life to the study of plant reproductive
      systems. He recognized that many of the intricacies of floral morphology had been
      shaped by natural selection in favour of outcrossing, and he clearly established
      the deleterious effects of self-fertilization on progeny. Although Darwin
      hypothesized the adaptive significance of self-fertilization under conditions of
      low mate availability, he held that a strategy of pure selfing would be strongly
      disadvantageous in the long term. Here, I briefly review these contributions to
      our understanding of plant reproduction. I then suggest that investigating two
      very different sexual systems, one in plants and the other in animals, would
      throw further light on the long-term implications of a commitment to reproduction
      exclusively by selfing.

PMID- 19386651
TI  - A new basal hadrosauroid dinosaur from the Late Cretaceous of Uzbekistan and the
      early radiation of duck-billed dinosaurs.
AB  - Levnesovia transoxiana gen. et sp. nov., from the Late Cretaceous (Middle-Late
      Turonian) of Uzbekistan, is the oldest well-documented taxon referable to
      Hadrosauroidea sensu Godefroit et al. It differs from a somewhat younger and
      closely related Bactrosaurus from Inner Mongolia (China) by a tall sagittal crest
      on the parietals and the absence of club-shaped dorsal neural spines in adult
      specimens. Levnesovia, Bactrosaurus and possibly Gilmoreosaurus represent the
      earliest radiation of Hadrosauroidea, which took place during the Cenomanian
      Turonian and possibly in North America. The second, Santonian-age radiation of
      Hadrosauroidea included Aralosaurus, Hadrosauridae and lineages leading to Tanius
      (Campanian) and Telmatosaurus (Maastrichtian). Hadrosauridae appears to be
      monophyletic, but Hadrosaurinae and Lambeosaurinae originated in North America
      and Asia, respectively.

PMID- 19386652
TI  - Do ants make direct comparisons?
AB  - Many individual decisions are informed by direct comparison of the alternatives.
      In collective decisions, however, only certain group members may have the
      opportunity to compare options. Emigrating ant colonies (Temnothorax albipennis)
      show sophisticated nest-site choice, selecting superior sites even when they are
      nine times further away than the alternative. How do they do this? We used radio
      frequency identification-tagged ants to monitor individual behaviour. Here we
      show for the first time that switching between nests during the decision process
      can influence nest choice without requiring direct comparison of nests. Ants
      finding the poor nest were likely to switch and find the good nest, whereas ants
      finding the good nest were more likely to stay committed to that nest. When ants
      switched quickly between the two nests, colonies chose the good nest. Switching
      by ants that had the opportunity to compare nests had little effect on nest
      choice. We suggest a new mechanism of collective nest choice: individuals respond
      to nest quality by the decision either to commit or to seek alternatives.
      Previously proposed mechanisms, recruitment latency and nest comparison, can be
      explained as side effects of this simple rule. Colony-level comparison and choice
      can emerge, without direct comparison by individuals.

PMID- 19386653
TI  - Social implications of the battle of the sexes: sexual harassment disrupts female
      sociality and social recognition.
AB  - Across sexually reproducing species, males and females are in conflict over the
      control of reproduction. At the heart of this conflict in a number of taxa is
      male harassment of females for mating opportunities and female strategies to
      avoid this harassment. One neglected consequence that may result from sexual
      harassment is the disruption of important social associations. Here, we
      experimentally manipulate the degree of sexual harassment that wild female
      guppies (Poecilia reticulata) experience by establishing replicated, semi-natural
      pools with different population sex ratios. We quantify the effects of sexual
      harassment on female social structure and the development of social recognition
      among females. When exposed to sexual harassment, we found that females had more
      disparate social networks with limited repeated interactions when compared to
      females that did not experience male harassment. Furthermore, females that did
      not experience harassment developed social recognition with familiar individuals
      over an 8-day period, whereas females that experienced harassment did not, an
      effect we suggest is due to disruption of association patterns. These results
      show that social network structure and social recognition can be affected by
      sexual harassment, an effect that will be relevant across taxonomic groups and
      that we predict will have fitness consequences for females.

PMID- 19386654
TI  - A longirostrine tyrannosauroid from the Early Cretaceous of China.
AB  - The fossil record of tyrannosauroid theropods is marked by a substantial temporal
      and morphological gap between small-bodied, Barremian taxa, and extremely large
      bodied taxa from the latest Cretaceous. Here we describe a new tyrannosauroid,
      Xiongguanlong baimoensis n. gen. et sp., from the Aptian-Albian Xinminpu Group of
      western China that represents a phylogenetic, morphological, and temporal link
      between these disjunct portions of tyrannosauroid evolutionary history.
      Xiongguanlong is recovered in our phylogenetic analysis as the sister taxon to
      Tyrannosauridae plus Appalachiosaurus, and marks the appearance of several
      tyrannosaurid hallmark features, including a sharp parietal sagittal crest, a
      boxy basicranium, a quadratojugal with a flaring dorsal process and a flexed
      caudal edge, premaxillary teeth bearing a median lingual ridge, and an expanded
      axial neural spine surmounted by distinct processes at its corners. Xiongguanlong
      is characterized by a narrow and elongate muzzle resembling that of Alioramus.
      The slender, unornamented nasals of Xiongguanlong are inconsistent with recent
      hypotheses of correlated progression in tyrannosauroid feeding mechanics, and
      suggest more complex patterns of character evolution in the integration of
      feeding adaptations in tyrannosaurids. Body mass estimates for the full-grown
      holotype specimen of Xiongguanlong fall between those of Late Cretaceous
      tyrannosaurids and Barremian tyrannosauroids, suggesting that the trend of
      increasing body size observed in North American Late Cretaceous Tyrannosauridae
      may extend through the Cretaceous history of Tyrannosauroidea though further
      phylogenetic work is required to corroborate this.

PMID- 19386655
TI  - A new tarkadectine primate from the Eocene of Inner Mongolia, China: phylogenetic
      and biogeographic implications.
AB  - Tarka and Tarkadectes are Middle Eocene mammals known only from the Rocky
      Mountains region of North America. Previous work has suggested that they are
      members of the Plagiomenidae, an extinct family often included in the order
      Dermoptera. Here we describe a new primate, Tarkops mckennai gen. et sp. nov.,
      from the early Middle Eocene Irdinmanha Formation of Inner Mongolia, China. The
      new taxon is particularly similar to Tarka and Tarkadectes, but it also displays
      many features observed in omomyids. A phylogenetic analysis based on a data
      matrix including 59 taxa and 444 dental characters suggests that Tarkops, Tarka
      and Tarkadectes form a monophyletic group--the Tarkadectinae--that is nested
      within the omomyid clade. Within Omomyidae, tarkadectines appear to be closely
      related to Macrotarsius. Dermoptera, including extant and extinct flying lemurs
      and plagiomenids, is recognized as a clade nesting within the polyphyletic group
      of plesiadapiforms, therefore supporting the previous suggestion that the
      relationship between dermopterans and primates is as close as that between
      plesiadapiforms and primates. The distribution of tarkadectine primates on both
      sides of the Pacific Ocean basin suggests that palaeoenvironmental conditions
      appropriate to sustain primates occurred across a vast expanse of Asia and North
      America during the Middle Eocene.

PMID- 19386656
TI  - Tensioning the helix: a mechanism for force generation in twining plants.
AB  - Twining plants use their helical stems to clasp supports and to generate a
      squeezing force, providing stability against gravity. To elucidate the mechanism
      that allows force generation, we measured the squeezing forces exerted by the
      twiner Dioscorea bulbifera while following its growth using time-lapse
      photography. We show that the development of the squeezing force is accompanied
      by stiffening of the stem and the expansion of stipules at the leaf base. We use
      a simple thin rod model to show that despite their small size and sparse
      distribution, stipules impose a stem deformation sufficient to account for the
      measured squeezing force. We further demonstrate that tensioning of the stem
      helix, although counter-intuitive, is the most effective mechanism for generating
      large squeezing forces in twining plants. Our observations and model point to a
      general mechanism for the generation of the twining force: a modest radial stem
      expansion during primary growth, or the growth of lateral structures such as leaf
      bases, causes a delayed stem tensioning that creates the squeezing forces
      necessary for twining plants to ascend their supports. Our study thus provides
      the long-sought answer to the question of how twining plants ascend smooth
      supports without the use of adhesive or hook-like structures.

PMID- 19386657
TI  - Many ways to be small: different environmental regulators of size generate
      distinct scaling relationships in Drosophila melanogaster.
AB  - Static allometries, the scaling relationship between body and trait size,
      describe the shape of animals in a population or species, and are generated in
      response to variation in genetic or environmental regulators of size. In
      principle, allometries may vary with the different size regulators that generate
      them, which can be problematic since allometric differences are also used to
      infer patterns of selection on morphology. We test this hypothesis by examining
      the patterns of scaling in Drosophila melanogaster subjected to variation in
      three environmental regulators of size: nutrition, temperature and rearing
      density. Our data indicate that different environmental regulators of size do
      indeed generate different patterns of scaling. Consequently, flies that are
      ostensibly the same size may have very different body proportions. These data
      indicate that trait size is not simply a read-out of body size, but that
      different environmental factors may regulate body and trait size, and the
      relationship between the two, through different developmental mechanisms. It may
      therefore be difficult to infer selective pressures that shape scaling
      relationships in a wild population without first elucidating the environmental
      and genetic factors that generate size variation among members of the population.

PMID- 19386658
TI  - A giant ornithomimosaur from the Early Cretaceous of China.
AB  - Ornithomimosaurs (ostrich-mimic dinosaurs) are a common element of some
      Cretaceous dinosaur assemblages of Asia and North America. Here, we describe a
      new species of ornithomimosaur, Beishanlong grandis, from an associated, partial
      postcranial skeleton from the Aptian-Albian Xinminpu Group of northern Gansu,
      China. Beishanlong is similar to another Aptian-Albian ornithomimosaur,
      Harpymimus, with which it shares a phylogenetic position as more derived than the
      Barremian Shenzhousaurus and as sister to a Late Cretaceous clade composed of
      Garudimimus and the Ornithomimidae. Beishanlong is one of the largest definitive
      ornithomimosaurs yet described, though histological analysis shows that the
      holotype individual was still growing at its death. Together with the co-eval and
      sympatric therizinosaur Suzhousaurus and the oviraptorosaur Gigantraptor,
      Beishanlong provides evidence for the parallel evolution of gigantism in separate
      lineages of beaked and possibly herbivorous coelurosaurs within a short time span
      in Central Asia.

PMID- 19386659
TI  - Thoracoscopic drainage of ascending mediastinitis arising from pancreatic
      pseudocyst.
AB  - Acute mediastinitis is a life-threatening disease. Common etiologies include
      surgical infection, esophageal perforation, and descending necrotizing
      mediastinitis from the oral cavity or pharynx. Mediastinitis caused by pancreatic
      disease is rare. The most common thoracic complication of pancreatic disease is
      reactive pleural effusion. We report a case of acute mediastinitis and bilateral
      empyema thoracis arising from a pancreatic pseudocyst. We utilized thoracoscopy
      to drain the mediastinum without drainage of the intra-abdominal cyst. The
      patient recovered well after operation.

PMID- 19386660
TI  - Aortic dissection due to sildenafil abuse.
AB  - This report deals with a 28-year-old male patient, admitted with a type A aortic
      dissection, potentially related to the use of sildenafil. In the literature, we
      found only two other potentially sildenafil-related cases of aortic dissections,
      one type A and one type B. In our patient, a bicuspid aortic valve and an
      ascending aortic aneurysm were other underlying anomalies that could have led to
      the aortic dissection.

PMID- 19386661
TI  - Preliminary results by flow-sensitive magnetic resonance imaging after Tiron
      David I procedure with an anatomically shaped ascending aortic graft.
AB  - We present preliminary data of the vascular hemodynamics in a novel, anatomically
      shaped ascending aortic graft in comparison to non-operated individuals by use of
      3D magnetic resonance (MR) flow measurements. We examined a 72-year-old male
      patient after Tiron David I valve sparing aortic root reconstruction and
      replacement of the ascending aorta (AAo) with an anatomically curved prosthesis.
      Results from flow-sensitive MR at 3T were compared to 12 age-matched individuals
      with comparable diameters of the AAo. For 3D flow visualization, streamlines and
      time-resolved particle traces were applied. A visual analysis of hemodynamic
      properties including blood flow helicity, vorticity and retrograde flow was
      performed. In contrast to reported highly disturbed flow of straight aortic
      grafts in the literature, the patient analysis revealed smooth blood flow through
      the graft which gave rise to a right-handed helical flow in the reconstructed
      aorta. In comparison to non-operated volunteers, blood flow helicity was more
      pronounced. Flow jets or vortices were not encountered. While physiological
      retrograde flow was seen in the volunteers, it was absent in the patient which
      may be explained by the altered aortic compliance and thus reduced Windkessel
      effect. This promising finding will have to prove its validity in further
      comparative studies.

PMID- 19386662
TI  - Neuropilin-mediated neural crest cell guidance is essential to organise sensory
      neurons into segmented dorsal root ganglia.
AB  - The peripheral nervous system (PNS) of higher vertebrates is segmented to align
      the spinal nerve roots with the vertebrae. This co-patterning is set up during
      embryogenesis, when vertebrae develop from the sclerotome layer of the metameric
      somites, and PNS neurons and glia differentiate from neural crest cells (NCCs)
      that preferentially migrate into the anterior sclerotome halves. Previous
      analyses of mice deficient in the class 3 semaphorin (SEMA3) receptors neuropilin
      (NRP) 1 or 2 raised the possibility that each controlled a distinct aspect of
      trunk NCC migration. We now demonstrate that both pathways act sequentially in
      distinct NCC subpopulations and thereby cooperate to enforce segmental NCC
      migration. Specifically, SEMA3A/NRP1 signalling first directs one population of
      NCCs from the intersomitic path into the sclerotome, and SEMA3F/NRP2 signalling
      acts subsequently to restrict a second population to the anterior half of the
      sclerotome. NCC exclusion from either the posterior sclerotome or the
      intersomitic boundary is sufficient to enforce the separation of neighbouring NCC
      streams and the segregation of sensory NCC progeny into metameric dorsal root
      ganglia (DRG). By contrast, the combined loss of both guidance pathways leads to
      ectopic invasion of the intersomitic furrows and posterior sclerotome halves,
      disrupting metameric NCC streaming and DRG segmentation.

PMID- 19386663
TI  - Hairy1 acts as a node downstream of Wnt signaling to maintain retinal stem cell
      like progenitor cells in the chick ciliary marginal zone.
AB  - In the vertebrate retina, stem cell-like progenitor cells are maintained in a
      distinct region called the ciliary marginal zone (CMZ). Canonical Wnt signaling
      regulates the maintenance of the progenitor cells in the CMZ. However, its
      downstream molecular mechanisms have remained largely unclear. Here, we show that
      chick Hairy1, an established Notch signaling effector, mediates the Wnt-dependent
      maintenance of CMZ progenitor cells in chicken. Interestingly, unlike other
      developmental contexts in which Hes gene expression is regulated by Notch
      signaling, Hairy1 expression in the CMZ is regulated by Wnt signaling. Hairy1 is
      necessary and sufficient for the expression of a set of molecular markers
      characteristic of the CMZ, and Wnt2b fails to induce CMZ markers when Hairy1
      activity is inhibited. Furthermore, microarray analysis identifies multiple Wnt
      responsive transcription factors that activate Hairy1 expression. We thus propose
      that Hairy1 functions as a node downstream of Wnt signaling to maintain
      progenitor cells in the chick CMZ.

PMID- 19386664
TI  - Preparation and evaluation of nimesulide-loaded ethylcellulose and
      methylcellulose nanoparticles and microparticles for oral delivery.
AB  - The present study was designed to assess and compare with a range of surfactant
      coated, nimesulide-free, and nimesulide-loaded ethylcellulose/methylcellulose
      (EC/MC) nanoparticles that were prepared by varying drug concentration (ED/MD),
      polymer concentration (EP/MP), and surfactant concentration (ES/MS). EC/MC
      nanoparticles prepared by desolvation method produced discrete particles and they
      were characterized by SEM, AFM, and FTIR studies. The particles mean size
      diameter (nm) ranged from 244 to 1056 nm and 1065 to 1710 nm for EC and MC
      nanoparticles, respectively. Studies on drug: polymer ratio showed a linear
      relationship between drug concentration and percentage of loading in
      nanoparticles. The encapsulation efficiency decreased with the increase of
      nimesulide concentration with respect to polymer concentration. Encapsulation
      efficiency of drug-loaded nanoparticles was varied between 32.8% and 64.9%. The
      in vitro release of drug-loaded nanoparticles was found to be a first order. This
      was significantly increased in EC nanoparticles (95.50%) in comparison with MC
      nanoparticles (95.12%) after 12 h in 24 h long study. Nimesulide release from EC
      nanoparticles was much slower at slightly alkaline pH 7.4. The in vitro hemolysis
      tests of nanoparticles were carried out to ascertain the hemocompatibility and
      shown to be insignificant for EC nanoparticles. In comparison, ES4 from EC
      formulations with nimesulide was found to be promising with slow and sustained
      drug release.

PMID- 19386665
TI  - Ectopic bone formation in adipose-derived stromal cell-seeded osteoinductive
      calcium phosphate scaffolds.
AB  - The phenomenon of osteoinduction by biomaterials has been proven and used in
      animals. However, whether the ability of a biomaterial to initiate bone formation
      in ectopic implantation sites improves the performance of such osteoinductive
      biomaterial as a scaffold for tissue-engineered (TE) bone remains unclear. In
      this study, we compared ectopic bone formation by combining autologous adipose
      derived stromal cells (ADSCs) with an osteoinductive and a nonosteoinductive
      biphasic calcium phosphate (BCP) ceramic to create a tissue engineering construct
      in the muscle of dogs. Two groups of BCP scaffolds (BCP1 and BCP2) were prepared.
      In each group, ADSCs were seeded, and the scaffolds without seeded cells served
      as controls. All implants were implanted in the back muscle of 10 adult dogs for
      8 weeks and 12 weeks. Microcomputed tomography (Micro-CT) analysis and
      histomorphometry were performed to evaluate and quantify ectopic bone formation.
      The results indicated that the osteoinductive BCP1 performed significantly better
      compared to the nonosteoinductive BCP2 in cell-based TE bone formation
      ectopically. The ADSCs had a significantly positive effect on the ectopic bone
      formation. In addition, the usefulness of Micro-CT for the efficient and
      nondestructive analysis of mineralized bone and calcium phosphate scaffold was
      confirmed.

PMID- 19386666
TI  - Development of self-assembled nanoceramic carrier construct(s) for vaccine
      delivery.
AB  - Hydroxyapatite (HA) has been extensively investigated as scaffolds for tissue
      engineering, as drug delivery agents, as non-viral gene carriers, as prosthetic
      coatings, and composites. Recent studies in our laboratory demonstrated the
      immunoadjuvant properties of HA when administered with malarial merozoite surface
      protein-1(19) (MSP-1(19)). HA nanoceramic carrier was prepared by co
      precipitation method that comprises of sintering and spray-drying technique.
      Prepared systems were characterized for crystallinity, size, shape, and antigen
      loading efficiency. Small size and large surface area of prepared HA demonstrated
      good adsorption efficiency of immunogens. Prepared nanoceramic formulations also
      showed slower in vitro antigen release and slower biodegrability behavior, which
      may lead to a prolonged exposure to antigen-presenting cells and lymphocytes.
      Furthermore, addition of mannose in nanoceramic formulation may additionally lead
      to increased stability and immunological reactions. Immunization with MSP-1(19)
      in nanoceramic-based adjuvant systems induced a vigorous immunoglobulin G (IgG)
      response, with higher IgG2a than IgG1 titers. In addition considerable amount of
      IFN-g and IL-2 was observed in spleen cells of mice immunized with nanoceramic
      based vaccines. On the contrary, mice immunized with MSP-1(19) alone or with alum
      did not exhibit a significant cytotoxic response. The antibody responses to
      vaccine co-administered with HA was a mixed Th1/Th2 compared to the Th2-biased
      response obtained with alum. The prepared HA nanoparticles exhibit
      physicochemical properties that appear promising to make them a suitable
      immunoadjuvant to be used as antigen carriers for immunopotentiation.

PMID- 19386667
TI  - Cytocompatibility and effect of increasing MgO content in a range of quaternary
      invert phosphate-based glasses.
AB  - Recently, phosphate-based glass (PBG) fibers have been used to reinforce the
      biodegradable polymers polycaprolactone and polylactic acid, in order to
      fabricate materials suitable for use as resorbable bone fracture fixation
      devices. However, the PBG fibers investigated tended to degrade too quickly for
      application. Therefore, more durable PBG formulations were sought with emphasis
      remaining firmly placed on their biocompatibility. In this study, four invert PBG
      formulations (in the system P2O5-CaO-MgO-Na2O) were produced with fixed phosphate
      and calcium content at 40 and 25 mol%, respectively. MgO was added at 10-30 mol%
      in place of Na2O and the maximum divalent cation to phosphate ratio obtained was
      1.375. Thermal analyses showed a linear increase in T(g) with increasing MgO
      content. This was proposed to be due to an increase in the cross-link density of
      the glass network, which also improved the chemical durability of the glass. EDX
      analyses were also conducted to verify the final composition of the glass. XRD
      analyses confirmed the amorphous nature of the glasses investigated. Rapid
      quenching of the Mg30 glass revealed a degree of surface crystallization, which
      was shown to be a CaMgP2O7 phase. The degradation rates of the glasses
      investigated decreased with increasing MgO content. The decrease in rate seen was
      almost two orders of magnitude (a x 50 difference was seen between glass Mg0 and
      Mg30). The cytocompatibility studies of the formulations investigated showed good
      cellular response over time for up to 14 days. Statistical analysis revealed that
      the formulations investigated gave a response comparable to the tissue culture
      plastic control. It is suggested that invert PBG provide degradation profiles and
      the cytocompatibility response desired to make these glasses useful for bone
      repair applications.

PMID- 19386668
TI  - Development of nanohydroxyapatite/polycarbonate composite for bone repair.
AB  - In this study, nano-hydroxyapatite (n-HA) combined polycarbonate was synthesized
      by a novel method. The physical and chemical property of the composite was
      tested. The results indicated the n-HA a crystal has the similar grain size,
      phase composition and crystal structure as. TEM photos results show the n-HA
      crystals were uniformly distributed in the polymer matrix. Then, the chemical
      bond between inorganic n-HA and polycarbonate was investigated and discussed.
      Proliferation of MSCs/composite cultured for up to 11 days the adhesion were
      tested by MTT and SEM. The in vitro test confirmed that the n-HA/PC composite was
      biocompatible and no negative effect on MSCs has found. The composite is proved
      to be osteoconductive, and can stimulate the growth of new bone. These results
      indicated that the composite meet the basic requirement of bone substitute
      material, and be potentially applied for clinic.

PMID- 19386669
TI  - A man with Wegener's granulomatosis and haemoptysis.

PMID- 19386672
TI  - Meeting information needs of patients with incurable progressive disease and
      their families in South Africa and Uganda: multicentre qualitative study.
AB  - OBJECTIVES: To explore the information needs of patients with progressive, life
      limiting disease and their family caregivers in South Africa and Uganda and to
      inform clinical practice and policy in this emerging field. DESIGN:
      Semistructured qualitative interview study. SETTING: Four palliative care
      services in South Africa and one in Uganda, covering rural, urban, and peri-urban
      locations. PARTICIPANTS: 90 patients and 38 family caregivers enrolled in
      palliative care services; 28 patients had cancer, 61 had HIV infection (including
      6 dual HIV/cancer diagnoses), and 1 had motor neurone disease. RESULTS: Five
      themes emerged from the data. (1) INFORMATION SOURCES: a lack of information from
      general healthcare providers meant that patients and caregivers had to draw on
      alternative sources of information. (2) Information needs: patients and
      caregivers reported needing more information in the key areas of the causes and
      progression of the disease, its symptoms and treatment, and financial/social
      support. (3) Impact of unmet needs: poor provision of information had a
      detrimental effect on patients' and caregivers' ability to cope. (4)
      Communication: negative experiences of communication with general healthcare
      staff were reported (misinformation, secrecy, insensitivity). (5) Barriers to
      effective provision of information: barriers related to symptoms, culture, time
      constraints in hospital, and paternalism in general health care. CONCLUSIONS:
      Lack of information was a major theme for both patients and carers, who had
      important unanswered questions relating to living with a progressive incurable
      disease. Evidence based recommendations for clinicians are presented, including
      the proactive provision of information tailored to individual patients and
      families.

PMID- 19386673
TI  - Diarrhoea and vomiting caused by gastroenteritis in children under 5 years:
      summary of NICE guidance.

PMID- 19386674
TI  - Perinatal mortality in the Netherlands.

PMID- 19386675
TI  - Strontium ranelate may cause alopecia.

PMID- 19386679
TI  - Six international research bodies form alliance to target chronic diseases.

PMID- 19386680
TI  - Malnutrition and hunger rise as economic crisis hits world's poorest people.

PMID- 19386681
TI  - Drug industry protests over need to register trial results.

PMID- 19386682
TI  - Incidence and aetiology of eosinophilic pleural effusion.
AB  - Although eosinophilic pleural effusion (EPE) has been a subject of numerous
      studies, its clinical significance still remains unclear. The aim of our study
      was to evaluate: 1) the relative incidence and aetiology of EPE; 2) the
      predictors of malignancy in patients with EPE; and 3) the relationship between
      repeated thoracentesis and pleural fluid eosinophilia. A retrospective analysis
      of 2,205 pleural fluid samples from 1,868 patients treated between 1995 and 2007
      was performed. We identified 135 patients with EPE (7.2% of all patients with
      pleural effusion) and 153 EPE samples. The most common condition associated with
      EPE was malignancy (34.8%) followed by infectious (19.2%), unknown (14.1%), post
      traumatic (8.9%) and miscellaneous (23.0%) pleural effusions. The incidence of
      malignancy was significantly higher in patients with a lower (< or =40%) pleural
      fluid eosinophil percentage. 40 patients with EPE underwent a second
      thoracentesis. In 16, eosinophilia was present in both pleural fluid samples, 14
      revealed pleural fluid eosinophilia only after the second thoracentesis and 10
      had eosinophilia only in the first pleural fluid sample. Pleural fluid
      eosinophilia should not be regarded as a predictor of nonmalignant aetiology.
      Probability of malignancy is lower in effusions with a high eosinophil
      percentage. The incidence of EPE in patients undergoing second thoracentesis is
      not different to that found during the first thoracentesis.

PMID- 19386683
TI  - Efficacy of moxifloxacin in the treatment of bronchial colonisation in COPD.
AB  - This study was designed to investigate the efficacy of moxifloxacin for the
      eradication of bacterial colonisation of the airways in patients with moderate-to
      severe chronic obstructive pulmonary disease (COPD). Out of 119 stable patients
      with COPD screened, 40 (mean age 69 yrs, mean forced expiratory volume in 1 s 50%
      predicted) were colonised with potentially pathogenic microorganisms (PPMs) and
      were included in a randomised, double-blind, placebo-controlled trial with
      moxifloxacin 400 mg daily for 5 days. Eradication rates were 75% with
      moxifloxacin and 30% with placebo at 2 weeks (p = 0.01). Bacterial persistence at
      8 weeks was still higher (not significantly) in the placebo arm (five (25%) out
      of 20 versus one (5%) out of 20; p = 0.18). The frequencies of acquisition of a
      new PPM were high and similar in both treatment groups; consequently, the
      prevalence of colonisation at 8 weeks was also similar between treatment arms. No
      difference was found in the number of patients with exacerbations during the 5
      month follow-up. Only the acquisition of a new PPM during follow-up showed a
      statistically significant relationship with occurrence of an exacerbation.
      Moxifloxacin was effective in eradicating PPMs in patients with positive sputum
      cultures. However, most patients were recolonised after 8 weeks of follow-up.
      Acquisition of a new strain of bacteria was associated with an increased risk of
      developing an exacerbation.

PMID- 19386684
TI  - Propofol versus combined sedation in flexible bronchoscopy: a randomised non
      inferiority trial.
AB  - Combined sedation with a benzodiazepine and an opiate has been proposed as
      standard sedation for bronchoscopy. Propofol is a sedative-hypnotic with a rapid
      onset of action and fast recovery time, but carries the potential risk of
      respiratory failure. Consecutive patients (n = 200) were randomly allocated to
      receive either the combination midazolam and hydrocodone or intravenous propofol.
      The primary end-points were the mean lowest arterial oxygen saturation during
      bronchoscopy and the readiness-for-discharge score 1 h after the procedure. The
      mean lowest arterial oxygen saturation during bronchoscopy did not differ across
      treatment groups (p = 0.422), and the number of patients recording an arterial
      oxygen saturation of < or =90% on at least one occasion was similar in both
      groups (p = 0.273). The median (interquartile range) readiness-for-discharge
      score 1 h after the procedure was significantly higher in the propofol group than
      in the combined sedation group (8 (6-9) versus 7 (5-9); p = 0.035). Patients
      assigned propofol exhibited less tachycardia during bronchoscopy and for > or =1
      h after the examination. Minor procedural complications were noted in 71 (35.5%)
      patients and exhibited a similar incidence in both treatment arms (p = 0.460).
      Propofol is as effective and safe as combined sedation in patients undergoing
      flexible bronchoscopy, thus representing an appealing option if timely discharge
      is a priority.

PMID- 19386685
TI  - Alveolar macrophages and CC chemokines are increased in children with cystic
      fibrosis.
AB  - Airway inflammation is an important component of cystic fibrosis (CF) lung
      disease. We sought to determine whether alveolar macrophages were involved in
      early CF lung disease. Children with CF (median age 3.1 yrs) participated in a
      surveillance programme that included annual bronchoalveolar lavage (BAL). Control
      samples were obtained from non-CF children (median age 3.1 yrs; n = 24)
      investigated for persistent respiratory symptoms. Pulmonary infection was
      detected in 31% (16 out of 51) and 38% (nine out of 24) of children from the CF
      and non-CF groups, respectively. Alveolar macrophages in BAL were increased in CF
      compared with non-CF in the absence of infection (223x10(3) versus 85x10(3)
      cells.mL(-1); p = 0.001) and were associated with elevations in the CC chemokines
      (macrophage inflammatory protein (MIP)-3alpha (chemokine (C-C motif) ligand
      (CCL)20; 355.8 versus 46.0 pg.mL(-1); p<0.001), monocyte chemotactic protein-1
      (CCL2; 263.5 versus 25.3 pg.mL(-1); p<0.001), MIP-1alpha (CCL3; 38.2 versus 4.9
      pg.mL(-1); p<0.001) and MIP-1beta (CCL4; 326.6 versus 27.5 pg.mL(-1); p<0.001)).
      Total cell counts and neutrophil numbers increased in the presence of infection;
      however, there was no additional effect of CF. Alveolar macrophages and CC
      chemokines are elevated in the lungs in young children with CF even in the
      absence of pulmonary infection. Longitudinal studies are required to determine
      the clinical relevance of these findings.

PMID- 19386686
TI  - CXCR3 ligands are augmented during the pathogenesis of pulmonary sarcoidosis.
AB  - We and other investigators have hypothesised that the CXC chemokine receptor
      (CXCR)3/CXCR3 ligand biological axis is involved in the formation of sarcoid lung
      granulomas; however, significant discrepancies in the current literature remain.
      In an effort to clarify previous conflicting findings, we performed the largest
      observational study to date of interferon-inducible ELR(-) (lacking the sequence
      glutamic acid-leucine-arginine) CXC chemokines in sarcoid bronchoalveolar fluid
      (BALF). BALF chemokine levels from sarcoid patients (n = 72) and healthy controls
      (n = 8) were measured with the ELISA method. Immunohistochemical staining was
      performed for CXCR3 and its ligands. BALF CXC chemokine ligand (CXCL)10 levels
      from sarcoid patients were not significantly increased compared with controls.
      BALF CXCL11 levels from sarcoid patients demonstrated a trend towards elevation;
      subgroup analysis by stage showed significant BALF CXCL11 elevation in stage I
      sarcoid patients compared with controls. BALF CXCL9 levels were elevated from
      sarcoid patients compared with controls. CXC11, CXCL9 and CXCR3 were expressed
      from epithelioid histiocytes, multinucleated giant cells and other inflammatory
      cells forming sarcoid lung granulomas. Our data suggest that CXCL9 and CXCL11 are
      important mediators in recruiting CXCR3-expressing cells. Importantly, we have
      made the novel observation that both lymphocytes and cells of monocyte linage
      express CXCR3 and are involved in the formation of sarcoid lung granulomas.

PMID- 19386687
TI  - CTLA4 gene polymorphisms are associated with chronic bronchitis.
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by chronic and
      progressive dyspnoea, cough and sputum production. T-lymphocytes may play a key
      role in the pathogenesis of COPD and chronic bronchitis. Cytotoxic T-lymphocyte
      antigen (CTLA) 4 is a potential candidate gene because it modulates T-cell
      activation. Genetic association between nine CTLA4 single nucleotide
      polymorphisms (SNPs) and chronic bronchitis was assessed in 606 pedigrees (1,896
      individuals) from the International COPD Genetics Network (ICGN) population. We
      then replicated the associations in 342 COPD subjects with chronic bronchitis and
      511 COPD subjects without chronic bronchitis from Bergen, Norway. Family-based
      association tests were used to analyse the ICGN cohort, and a logistic regression
      model was used for the Bergen cohort. Six CTLA4 SNPs were significantly
      associated with chronic bronchitis in the ICGN cohort (0.0079< or = p < or
      =0.0432), with three being replicated with the same directionality of association
      in the Bergen cohort (0.0325< or = p < or =0.0408). One of these replicated SNPs
      (rs231775) encodes the Thr to Ala substitution at amino acid position 17.
      Haplotype analyses supported the results of single SNP analyses. Thus, CTLA4 is
      likely to be a genetic determinant of chronic bronchitis among COPD cases.

PMID- 19386688
TI  - Azithromycin has an antiproliferative and autophagic effect on airway smooth
      muscle cells.
AB  - Azithromycin is used in long-term, low-dose treatment of airway diseases where
      airway wall remodelling is present. Since it improves total score symptom and
      respiratory function of such patients, we hypothesise that azithromycin's
      additional clinical benefits are due to an inhibition of airway smooth muscle
      cell (SMC) proliferation. Rabbit tracheal SMCs were treated with azithromycin
      (10(-5) to 10(-6) M) in the presence or absence of 10% fetal bovine serum (FBS).
      The proliferation was estimated using the Cell Titer 96(R) AQ(ueous) One Solution
      Assay (Promega, Madison, WI, USA). Cell viability was assessed with Trypan blue
      staining and flow cytometry after 7-aminoactinomycin D (7-AAD) staining.
      Induction of autophagy was studied by indirect immmunofluorescence and/or Western
      blotting with antibodies against human smooth muscle alpha-actin, beclin 1, light
      chain 3 and caspase 3. The involvement of the phosphoinositide 3-kinase pathway
      was investigated with the inhibitors LY294002 and wortmannin. Incubation with
      azithromycin for 72 h in the presence of FBS reduced SMC proliferation and
      viability in a dose-dependent manner. Azithromycin treatment was accompanied by
      the formation of cytoplasmic vacuoles, characteristic of autophagy. All these
      effects were reversible after azithromycin removal and prevented by the autophagy
      inhibitor, 3-methyladenine, or LY294002, but not by wortmannin. In conclusion,
      azithromycin reduces proliferation and causes autophagy of airway SMCs.

PMID- 19386689
TI  - Clinical relevance of Mycobacterium malmoense isolation in The Netherlands.
AB  - Uncertainty exists about the clinical relevance of Mycobacterium malmoense
      isolation, especially in pulmonary samples. We therefore determined clinical
      relevance, treatment and outcome of M. malmoense isolation in The Netherlands. A
      retrospective medical file study was conducted for all patients in The
      Netherlands from whom Mycobacterium malmoense had been isolated between January
      2002 and January 2006. Diagnostic criteria for nontuberculous mycobacterial (NTM)
      disease published by the American Thoracic Society (ATS) were used to determine
      clinical relevance. Treatment was compared with guidelines published by the
      British Thoracic Society. In total, 51 patients were found from whom M. malmoense
      was isolated. Of these, 40 (78%) patients had pulmonary isolates and 32 (80%) of
      them met the ATS diagnostic criteria. Cavitary disease was most common (n = 28;
      88%). Patients with pulmonary disease were mostly males, with an average age of
      56 yrs and pre-existing chronic obstructive pulmonary disease. Cervical
      lymphadenitis was the most common extrapulmonary disease type. Adherence to
      treatment guidelines was poor. A good clinical response to treatment was observed
      in 70% and 73% of patients treated for pulmonary and extrapulmonary disease,
      respectively. In conclusion, M. malmoense is a clinically highly relevant NTM in
      The Netherlands causing serious pulmonary morbidity. Adherence to treatment
      guidelines is not satisfactory.

PMID- 19386690
TI  - Seasonality of tuberculosis in an Eastern-Asian country with an extreme
      continental climate.
AB  - Aggregate monthly notifications of incident sputum smear-positive tuberculosis
      (TB) in Mongolia, stratified by sex and age groups, were analysed separately for
      Ulaanbaatar, Mongolia, and the rest of the country for the 9-yr period from 1998
      to 2006. TB notifications were compared with ambient surface temperature. More
      than twice as many TB cases were notified in the peak month (April) compared with
      the trough months (October-December), paralleling the temperature curve. The
      fluctuations recurred consistently over the entire observation period, were
      identical in the capital compared with the rest of the country, and were
      independent of age and sex. TB notifications parallel the temperature amplitudes
      and have a magnitude not reported elsewhere. We hypothesise that the influence of
      temperature on life either indoors or outdoors is consistent with the
      transmission probability of Mycobacterium tuberculosis and the subsequent delay
      to disease recognition and notification with the incubation period, possibly co
      determined by other factors, rather than accessibility to services.

PMID- 19386691
TI  - Screening for pulmonary and cerebral arteriovenous malformations in children with
      hereditary haemorrhagic telangiectasia.
AB  - Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease
      characterised by vascular dysplasia complicated by visceral arteriovenous
      malformations (AVMs). To date, the diagnostic yield of screening procedures for
      pulmonary and cerebral AVMs in children with definite or potential HHT is not
      well defined. The aim of the present study was to prospectively evaluate the
      diagnostic yield of a screening protocol for pulmonary and cerebral AVMs in
      children with either a definite or potential HHT diagnosis. All children referred
      for evaluation for HHT between 1996 and 2008 were included in the present
      analysis. Screening tests for AVMs included chest computed tomography and brain
      magnetic resonance imaging. 61 children with a definite clinical and/or genetic
      diagnosis of HHT were asymptomatic for visceral AVMs at their first baseline
      assessment (mean+/-SD age 8.7+/-4.7 yrs; range 0-17.0 yrs). Of these, 15 (25%)
      had pulmonary and/or cerebral AVMs diagnosed on initial screening tests.
      Pulmonary AVMs predominated in paediatric HHT patients (14 out of 15 patients)
      and were found in eight children aged <10 yrs. 55 children had a potential HHT
      diagnosis as they fulfilled only one or two HHT clinical diagnostic criteria and
      did not have a confirmatory genetic diagnosis (age 10.9+/-4.8 yrs; range 0-17.9
      yrs). None of these children had pulmonary or cerebral AVMs on initial screening
      tests. The present data suggest that children with a definite HHT diagnosis have
      a high frequency of pulmonary AVMs even when clinically asymptomatic. In
      contrast, no AVMs were observed in children not fulfilling HHT diagnostic
      criteria. Genetic testing appears to be useful in defining an at-risk group for
      pulmonary AVMs in childhood.

PMID- 19386692
TI  - Impaired detection of Mycobacterium tuberculosis immunity in patients using high
      levels of immunosuppressive drugs.
AB  - We have previously shown, in renal transplant recipients on maintenance
      immunosuppression, that a whole-blood assay was superior in detecting immunity
      towards purified protein derivative (PPD) compared with skin testing. As blood
      tests may have limitations during high-dose immunosuppression therapy, the
      present study was aimed at characterising the effect of high immunosuppressive
      drug levels on PPD-specific T-cell immunity. PPD-reactive CD4 T-cells from 13
      renal transplant recipients were longitudinally quantified by the induction of
      cytokines using flow cytometry. To further address the effect of high and low
      maintenance immunosuppression, drug effects were studied in vitro and in 49 age
      matched lung transplant recipients and 49 renal transplant recipients.
      Maintenance immunosuppression after renal transplantation did not affect PPD
      specific T-cell detection (median T-cell frequencies 0.55% before and 0.46% >12
      months after transplantation), whereas specific T-cell frequencies were
      significantly lower 3 months after transplantation (0.15%; p = 0.0002). Likewise,
      high-level maintenance immunosuppression after lung transplantation was
      associated with a significantly lower prevalence in PPD-specific T-cell
      reactivity compared with renal transplant recipients (16.7% versus 52.1%; p =
      0.0005). In line with the observations made in vivo, calcineurin inhibitors
      analysed in vitro led to a dose-dependent decrease in antigen-specific T-cell
      reactivity. The flow cytometric assay is not adversely affected by low drug
      doses. In contrast, decreased levels of PPD-specific T-cells early after
      transplantation and low prevalence of PPD-reactivity in lung transplant
      recipients suggest a reduced sensitivity of in vitro testing during high-level
      immunosuppression.

PMID- 19386693
TI  - Utility of quantitative T-cell responses versus unstimulated interferon-{gamma}
      for the diagnosis of pleural tuberculosis.
AB  - The clinical utility of antigen-specific interferon (IFN)-gamma release assays
      (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB),
      requires clarification. We compared the diagnostic utility of unstimulated
      pleural IFN-gamma levels with several pleural antigen-specific T-cell IGRAs
      (early secretory antigenic target-6 and culture filtrate protein-10 (T
      SPOT.(R)TB, QuantiFERON(R)-TB Gold In-tube), purified protein derivative (PPD)
      and heparin-binding haemagglutinin (HBHA)) in 78 South African TB suspects. Test
      results were compared against a clinical score and a reference standard. Out of
      74 evaluable subjects 48, seven and 19 had definite, probable and no TB,
      respectively. 11 (15%) out of 74 pleural samples (nine (19%) out of 48 of the
      definite TB cases) had total cell counts that were inadequate for T-cell
      processing. In the remaining 63 samples, the sensitivity, specificity, positive
      predictive value and negative predictive value of different diagnostic methods
      were as follows. Maximal bioclinical score: 54, 89, 92 and 43%, respectively; T
      SPOT.(R)TB: 86, 60, 84 and 64%, respectively; QuantiFERON(R)-TB Gold In-tube: 57,
      80, 87 and 44%, respectively; HBHA-specific IGRA: 59, 31, 64 and 27%,
      respectively; PPD-specific IGRA: 81, 40, 76 and 46%, respectively; and pleural
      fluid unstimulated IFN-gamma: 97, 100, 100 and 94%, respectively. Unstimulated
      IFN-gamma was the most accurate test for distinguishing TB from non-TB effusions
      in a high-burden setting. The antigen-specific T-cell IGRAs were limited by
      suboptimal accuracy and the inability to isolate sufficient mononuclear cells to
      perform the assay.

PMID- 19386694
TI  - Pseudomonas aeruginosa in patients hospitalised for COPD exacerbation: a
      prospective study.
AB  - Risk factors for Pseudomonas aeruginosa (PA) isolation in patients hospitalised
      for chronic obstructive pulmonary disease (COPD) exacerbation remain
      controversial. The aim of our study was to determine the incidence and risk
      factors for PA isolation in sputum at hospital admission in a prospective cohort
      of patients with acute exacerbation of COPD. We prospectively studied all
      patients with COPD exacerbation admitted to our hospital between June 2003 and
      September 2004. Suspected predictors of PA isolation were studied. Spirometry
      tests and 6-min walking tests were performed 1 month after the patients were
      discharged. High-resolution computed tomography (HRCT) was performed in a
      randomised manner in one out of every two patients to quantify the presence and
      extent of bronchiectasis. Patients were followed up during the following year for
      hospital re-admissions. A total of 188 patients were included, of whom 31 (16.5%)
      had PA in sputum at initial admission. The BODE (body mass index, airflow
      obstruction, dyspnoea, exercise capacity) index (OR 2.18, CI 95% 1.26-3.78; p =
      0.005), admissions in the previous year (OR 1.65, CI 95% 1.13-2.43; p = 0.005),
      systemic steroid treatment (OR 14.7, CI 95% 2.28-94.8; p = 0.01), and previous
      isolation of PA (OR 23.1, CI 95% 5.7-94.3; p<0.001) were associated with PA
      isolation. No relationship was seen between bronchiectasis in HRCT and antibiotic
      use in the previous 3 months. PA in sputum at hospital admission is more frequent
      in patients with poorer scoring on the BODE index, previous hospital admissions,
      oral corticosteroids and prior isolation of PA.

PMID- 19386695
TI  - Water taste transduction pathway is calcium dependent in Drosophila.
AB  - In mammals, detection of osmolarity by the gustatory system was overlooked until
      recently. In insects, specific taste receptor neurons detect hypoosmotic stimuli
      and are commonly called "W" (water) cells. W cells are easy to access in vivo and
      represent a good model to study the transduction of hypoosmotic stimuli. Using
      pharmacological and genetic approaches in Drosophila, we show that tarsal W cell
      firing activity depends on the concentration of external calcium bathing the
      dendrite. This dependence was confirmed by the strong inhibition of W cell
      responses to hypoosmotic stimuli by lanthanum (IC(50) = 8 nM), an ion known to
      inhibit calcium-permeable channels. Downstream, the transduction pathway likely
      involves calmodulin because calmodulin antagonists such as W-7 (IC(50) = 2
      microM) and fluphenazine (IC(50) = 30 microM) prevented the activation of the W
      cell by hypoosmotic stimuli. A protein kinase C (PKC) may also be involved as W
      cell responses were blocked by PKC inhibitors, chelerythrine (IC(50) = 20 microM)
      and staurosporine (IC(50) = 30 microM). It was also reduced when expressing an
      inhibitory pseudosubstrate of PKC in gustatory receptor neurons. In the rat, the
      transduction pathway underlying low osmolarity detection involves aquaporin and
      swelling-activated ion channels. Our study suggests that the transduction pathway
      of hypoosmotic stimuli in insects differs from mammals.

PMID- 19386697
TI  - IL-10 protects monocytes and macrophages from complement-mediated lysis.
AB  - Phagocytes, such as monocytes and macrophages, are important cells of the innate
      immunity in the defense against microbes. So far, it is unclear how these cells
      survive at the site of combat against microbes, where a hostile inflammatory
      environment prevails with strong complement activity. We hypothesized that IL-10,
      a key cytokine involved in the resolution of inflammation, induces resistance to
      complement attack. Here, we demonstrate for the first time such a cell-protective
      effect of IL-10 on human monocytes and macrophages. IL-10 is indeed able to
      protect these cell types in an in vitro model of complement lysis triggered by an
      anti-MHCI antibody or by binding of zymosan. Investigating potential underlying
      mechanisms, we found that IL-10 up-regulated the expression of complement
      regulatory membrane protein CD59 and the general cell-protective stress protein
      HO-1 in human monocytes. However, further functional analysis failed to link
      these individual IL-10-mediated effects with the increased protection from
      complement lysis. Blocking the protective effect of CD59 with an antibody
      increased complement lysis but did not abrogate the IL-10-protective effect.
      Interestingly, chemical interference with HO-1 activity did abrogate the
      protective effect of IL-10, but siRNA-mediated knockdown of HO-1 did not confirm
      this observation. Our results suggest that IL-10 generates pathogen-clearing
      phagocytes, which are resistant to complement lysis and thereby, enabled to
      survive longer in a hostile inflammatory environment.

PMID- 19386698
TI  - Mer tyrosine kinase (MerTK) promotes macrophage survival following exposure to
      oxidative stress.
AB  - The MerTK plays several important roles in normal macrophage physiology,
      including regulation of cytokine secretion and clearance of apoptotic cells. Mer
      signaling in other cell types, including malignant cells that ectopically
      overexpress the RTK, leads to downstream prosurvival pathway activation. We
      explored the hypothesis that Mer has a prosurvival role in macrophages exposed to
      oxidative stress. H(2)O(2) treatment of peritoneal exudate murine macrophages and
      J774 cells rapidly stimulated Mer phosphorylation in a concentration-dependent
      manner. Mer phosphorylation was dependent on the ligand Gas6, as treatment with
      warfarin or MerFc (a fusion protein of the extracellular domain of Mer and the Fc
      portion of human Ig), inhibitors of Gas6 activity, blocked H(2)O(2)-mediated
      activation of Mer. Antiapoptotic signals including pAkt and pErk 1/2 were
      increased dramatically (threefold and 4.5-fold, respectively) in WT Mer-positive
      macrophages compared with Mer KO macrophages stimulated with H(2)O(2). In a
      consistent manner, Mer expression led to decreased cleavage of proapoptotic
      indicators PARP and Caspase-3. Furthermore, Mer provided up to twofold enhanced
      cellular survival to primary macrophages exposed to H(2)O(2). These data
      represent the first report of Mer activation in response to oxidative stress and
      demonstrate the ability of Mer RTK to promote macrophage survival in disease
      states that involve an oxidative stress environment.

PMID- 19386699
TI  - Lymphocyte and antibody responses reduce enterovirus 71 lethality in mice by
      decreasing tissue viral loads.
AB  - Enterovirus 71 (EV71) infects the central nervous system and causes death and
      long-term neurological sequelae in hundreds of thousands of young children, but
      its pathogenesis remains elusive. Immunopathological mechanisms have been
      suspected to contribute to the pathogenesis of neurological symptoms, so anti
      inflammatory agents have been used to treat patients with neurological symptoms.
      The present study was therefore designed to investigate the functions of
      lymphocyte and antibody responses in EV71 infection using a mouse model.
      Immunohistochemical staining analysis revealed virus and three types of
      lymphocytes, B cells, CD4 T cells, and CD8 T cells, in the spinal cord of an EV71
      infected patient who died. A study of mice showed that the levels of virus and
      lymphocytes in brains and antibody titers in sera were elevated during the time
      when the mice succumbed to death in a phenomenon analogous to that observed in
      patients. Further studies demonstrated that after infection, the disease
      severity, mortality, and tissue viral loads of mice deficient in B, CD4 T, or CD8
      T cells were significantly higher than those of wild-type mice. In addition,
      treatment with a virus-specific antibody, but not a control antibody, before or
      after infection significantly reduced the disease severity, mortality, and tissue
      viral loads of mice deficient in B cells. Our results show that both lymphocyte
      and antibody responses protect mice from EV71 infection. Our study suggests the
      use of vaccines and virus-specific antibodies to control fatal outbreaks and
      raises caution over the use of corticosteroids to treat EV71-infected patients
      with neurological symptoms.

PMID- 19386700
TI  - A point mutation, E95D, in the mumps virus V protein disengages STAT3 targeting
      from STAT1 targeting.
AB  - Mumps virus, like other paramyxoviruses in the Rubulavirus genus, encodes a V
      protein that can assemble a ubiquitin ligase complex from cellular components,
      leading to the destruction of cellular signal transducer and activator of
      transcription (STAT) proteins. While many V proteins target the interferon
      activated STAT1 or STAT2 protein, mumps virus V protein is unique in its ability
      to also target STAT3 for ubiquitin modification and proteasome-mediated
      degradation. Here we report that a single amino acid substitution in the mumps
      virus V protein, E95D, results in defective STAT3 targeting while maintaining the
      ability to target STAT1. Results indicate that the E95D mutation disrupts the
      ability of the V protein to associate with STAT3. A recombinant mumps virus
      carrying the E95D mutation in its P and V proteins replicates normally in
      cultured cells but fails to induce targeting of STAT3. Infection with the
      recombinant virus results in the differential regulation of a number of cellular
      genes compared to wild-type mumps virus and increases cell death in infected
      cells, producing a large-plaque phenotype.

PMID- 19386701
TI  - The respiratory syncytial virus M2-1 protein forms tetramers and interacts with
      RNA and P in a competitive manner.
AB  - The respiratory syncytial virus (RSV) M2-1 protein is an essential cofactor of
      the viral RNA polymerase complex and functions as a transcriptional processivity
      and antitermination factor. M2-1, which exists in a phosphorylated or
      unphosphorylated form in infected cells, is an RNA-binding protein that also
      interacts with some of the other components of the viral polymerase complex. It
      contains a CCCH motif, a putative zinc-binding domain that is essential for M2-1
      function, at the N terminus. To gain insight into its structural organization, M2
      1 was produced as a recombinant protein in Escherichia coli and purified to >95%
      homogeneity by using a glutathione S-transferase (GST) tag. The GST-M2-1 fusion
      proteins were copurified with bacterial RNA, which could be eliminated by a high
      salt wash. Circular dichroism analysis showed that M2-1 is largely alpha-helical.
      Chemical cross-linking, dynamic light scattering, sedimentation velocity, and
      electron microscopy analyses led to the conclusion that M2-1 forms a 5.4S
      tetramer of 89 kDa and approximately 7.6 nm in diameter at micromolar
      concentrations. By using a series of deletion mutants, the oligomerization domain
      of M2-1 was mapped to a putative alpha-helix consisting of amino acid residues 32
      to 63. When tested in an RSV minigenome replicon system using a luciferase gene
      as a reporter, an M2-1 deletion mutant lacking this region showed a significant
      reduction in RNA transcription compared to wild-type M2-1, indicating that M2-1
      oligomerization is essential for the activity of the protein. We also show that
      the region encompassing amino acid residues 59 to 178 binds to P and RNA in a
      competitive manner that is independent of the phosphorylation status of M2-1.

PMID- 19386702
TI  - Single-injection vaccine protects nonhuman primates against infection with
      marburg virus and three species of ebola virus.
AB  - The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with
      high mortality in humans and nonhuman primates. Among the most promising
      filovirus vaccines under development is a system based on recombinant vesicular
      stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in
      place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in
      order to determine the potential of having one single-injection vaccine capable
      of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire
      ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV).
      In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine
      consisting of equal parts of the vaccine vectors VSVDeltaG/SEBOVGP,
      VSVDeltaG/ZEBOVGP, and VSVDeltaG/MARVGP. Four weeks later, three of these animals
      were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with
      SEBOV. Three control animals were vaccinated with VSV vectors encoding a
      nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and
      five unvaccinated control animals were challenged with CIEBOV. Importantly, none
      of the macaques vaccinated with the blended vaccine succumbed to a filovirus
      challenge. As expected, an experimental control animal vaccinated with
      VSVDeltaG/ZEBOVGP and challenged with SEBOV succumbed, as did the positive
      controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control
      animals challenged with CIEBOV became severely ill, and three of the animals
      succumbed on days 12, 12, and 14, respectively. The two animals that survived
      CIEBOV infection were protected from subsequent challenge with either SEBOV or
      ZEBOV, suggesting that immunity to CIEBOV may be protective against other species
      of Ebola virus. In conclusion, we developed an immunization scheme based on a
      single-injection vaccine that protects nonhuman primates against lethal challenge
      with representative strains of all human pathogenic filovirus species.

PMID- 19386703
TI  - Herpesvirus capsid association with the nuclear pore complex and viral DNA
      release involve the nucleoporin CAN/Nup214 and the capsid protein pUL25.
AB  - After penetrating the host cell, the herpesvirus capsid is transported to the
      nucleus along the microtubule network and docks to the nuclear pore complex
      before releasing the viral DNA into the nucleus. The viral and cellular
      interactions involved in the docking process are poorly characterized. However,
      the minor capsid protein pUL25 has recently been reported to be involved in viral
      DNA uncoating. Here we show that herpes simplex virus type 1 (HSV-1) capsids
      interact with the nucleoporin CAN/Nup214 in infected cells and that RNA silencing
      of CAN/Nup214 delays the onset of viral DNA replication in the nucleus. We also
      show that pUL25 interacts with CAN/Nup214 and another nucleoporin, hCG1, and
      binds to the pUL36 and pUL6 proteins, two other components of the herpesvirus
      particle that are known to be important for the initiation of infection and viral
      DNA release. These results identify CAN/Nup214 as being a nuclear receptor for
      the herpesvirus capsid and pUL25 as being an interface between incoming capsids
      and the nuclear pore complex and as being a triggering element for viral DNA
      release into the nucleus.

PMID- 19386704
TI  - Human monoclonal antibodies against West Nile virus induced by natural infection
      neutralize at a postattachment step.
AB  - West Nile virus (WNV) is a neurotropic flavivirus that is now a primary cause of
      epidemic encephalitis in North America. Studies of mice have demonstrated that
      the humoral immune response against WNV limits primary infection and protects
      against a secondary challenge. The most-potent neutralizing mouse monoclonal
      antibodies (MAbs) recognize an epitope on the lateral ridge of domain III (DIII
      lr) of the envelope (E) protein. However, studies with serum from human patients
      show that antibodies against the DIII-lr epitope comprise, at best, a minor
      component of the human anti-WNV antibody response. Herein, we characterize in
      detail two WNV-specific human MAbs, CR4348 and CR4354, that were isolated from B
      cell populations of convalescent patients. These MAbs strongly neutralize WNV
      infection of cultured cells, protect mice against lethal infection in vivo, and
      yet poorly recognize recombinant forms of the E protein. Instead, CR4348 and
      CR4354 bind determinants on intact WNV virions and subviral particles in a pH
      sensitive manner, and neutralization is altered by mutations at the dimer
      interface in domain II and the hinge between domains I and II, respectively.
      CR4348 and CR4354 human MAbs neutralize infection at a postattachment step in the
      viral life cycle, likely by inhibiting acid-induced fusion within the endosome.

PMID- 19386705
TI  - Critical role of cyclophilin A and its prolyl-peptidyl isomerase activity in the
      structure and function of the hepatitis C virus replication complex.
AB  - Replication of hepatitis C virus (HCV) RNA occurs on intracellular membranes, and
      the replication complex (RC) contains viral RNA, nonstructural proteins, and
      cellular cofactors. We previously demonstrated that cyclophilin A (CyPA) is an
      essential cofactor for HCV infection and the intracellular target of
      cyclosporine's anti-HCV effect. Here we investigate the mechanism by which CyPA
      facilitates HCV replication. Cyclosporine treatment specifically blocked the
      incorporation of NS5B into the RC without affecting either the total protein
      level or the membrane association of the protein. Other nonstructural proteins or
      viral RNAs in the RC were not affected. NS5B from the cyclosporine-resistant
      replicon was resistant to this disruption of RC incorporation. We also isolated
      membrane fractions from both naive and HCV-positive cells and found that CyPA is
      recruited into membrane fractions in HCV-replicating cells via an interaction
      with RC-associated NS5B, which is sensitive to cyclosporine treatment. Finally,
      we introduced point mutations in the prolyl-peptidyl isomerase (PPIase) motif of
      CyPA and demonstrated a critical role of this motif in HCV replication in cDNA
      rescue experiments. We propose a model in which the incorporation of the HCV
      polymerase into the RC depends on its interaction with a cellular chaperone
      protein and in which cyclosporine inhibits HCV replication by blocking this
      critical interaction and the PPIase activity of CyPA. Our results provide a
      mechanism of action for the cyclosporine-mediated inhibition of HCV and identify
      a critical role of CyPA's PPIase activity in the proper assembly and function of
      the HCV RC.

PMID- 19386706
TI  - The crystal structures of Chikungunya and Venezuelan equine encephalitis virus
      nsP3 macro domains define a conserved adenosine binding pocket.
AB  - Macro domains (also called "X domains") constitute a protein module family
      present in all kingdoms of life, including viruses of the Coronaviridae and
      Togaviridae families. Crystal structures of the macro domain from the Chikungunya
      virus (an "Old World" alphavirus) and the Venezuelan equine encephalitis virus (a
      "New World" alphavirus) were determined at resolutions of 1.65 and 2.30 A,
      respectively. These domains are active as adenosine di-phosphoribose 1''
      phosphate phosphatases. Both the Chikungunya and the Venezuelan equine
      encephalitis virus macro domains are ADP-ribose binding modules, as revealed by
      structural and functional analysis. A single aspartic acid conserved through all
      macro domains is responsible for the specific binding of the adenine base.
      Sequence-unspecific binding to long, negatively charged polymers such as poly(ADP
      ribose), DNA, and RNA is observed and attributed to positively charged patches
      outside of the active site pocket, as judged by mutagenesis and binding studies.
      The crystal structure of the Chikungunya virus macro domain with an RNA trimer
      shows a binding mode utilizing the same adenine-binding pocket as ADP-ribose, but
      avoiding the ADP-ribose 1''-phosphate phosphatase active site. This leaves the
      AMP binding site as the sole common feature in all macro domains.

PMID- 19386707
TI  - Infection of HLA-DR1 transgenic mice with a human isolate of influenza a virus
      (H1N1) primes a diverse CD4 T-cell repertoire that includes CD4 T cells with
      heterosubtypic cross-reactivity to avian (H5N1) influenza virus.
AB  - The specificity of the CD4 T-cell immune response to influenza virus is
      influenced by the genetic complexity of the virus and periodic encounters with
      variant subtypes and strains. In order to understand what controls CD4 T-cell
      reactivity to influenza virus proteins and how the influenza virus-specific
      memory compartment is shaped over time, it is first necessary to understand the
      diversity of the primary CD4 T-cell response. In the study reported here, we have
      used an unbiased approach to evaluate the peptide specificity of CD4 T cells
      elicited after live influenza virus infection. We have focused on four viral
      proteins that have distinct intracellular distributions in infected cells,
      hemagglutinin (HA), neuraminidase (NA), nucleoprotein, and the NS1 protein, which
      is expressed in infected cells but excluded from virion particles. Our studies
      revealed an extensive diversity of influenza virus-specific CD4 T cells that
      includes T cells for each viral protein and for the unexpected immunogenicity of
      the NS1 protein. Due to the recent concern about pandemic avian influenza virus
      and because CD4 T cells specific for HA and NA may be particularly useful for
      promoting the production of neutralizing antibody to influenza virus, we have
      also evaluated the ability of HA- and NA-specific CD4 T cells elicited by a
      circulating H1N1 strain to cross-react with related sequences found in an avian
      H5N1 virus and find substantial cross-reactivity, suggesting that seasonal
      vaccines may help promote protection against avian influenza virus.

PMID- 19386708
TI  - Human parainfluenza virus infection of the airway epithelium: viral hemagglutinin
      neuraminidase regulates fusion protein activation and modulates infectivity.
AB  - Three discrete activities of the paramyxovirus hemagglutinin-neuraminidase (HN)
      protein, receptor binding, receptor cleaving (neuraminidase), and triggering of
      the fusion protein, each affect the promotion of viral fusion and entry. For
      human parainfluenza virus type 3 (HPIV3), the effects of specific mutations that
      alter these functions of the receptor-binding protein have been well
      characterized using cultured monolayer cells, which have identified steps that
      are potentially relevant to pathogenesis. In the present study, proposed
      mechanisms that are relevant to pathogenesis were tested in natural host cell
      cultures, a model of the human airway epithelium (HAE) in which primary HAE cells
      are cultured at an air-liquid interface and retain functional properties.
      Infection of HAE cells with wild-type HPIV3 and variant viruses closely reflects
      that seen in an animal model, the cotton rat, suggesting that HAE cells provide
      an ideal system for assessing the interplay of host cell and viral factors in
      pathogenesis and for screening for inhibitory molecules that would be effective
      in vivo. Both HN's receptor avidity and the function and timing of F activation
      by HN require a critical balance for the establishment of ongoing infection in
      the HAE, and these HN functions independently modulate the production of active
      virions. Alterations in HN's F-triggering function lead to the release of
      noninfectious viral particles and a failure of the virus to spread. The finding
      that the dysregulation of F triggering prohibits successful infection in HAE
      cells suggests that antiviral strategies targeted to HN's F-triggering activity
      may have promise in vivo.

PMID- 19386709
TI  - Activated Ras/MEK inhibits the antiviral response of alpha interferon by reducing
      STAT2 levels.
AB  - The ability of interferon (IFN) to induce the expression of antiviral genes, and
      therefore suppress viral infection, is dependent on the activity of cellular
      suppressors. The Ras/MEK pathway is one of these cellular suppressors, since the
      activation of Ras/MEK permits viral replication in the presence of alpha IFN (IFN
      alpha). Here, we have investigated the mechanism by which activated Ras/MEK
      inhibits the IFN-alpha response. We found that the induction of antiviral
      proteins in response to IFN-alpha was impaired in Ras-transformed NIH 3T3
      (RasV12) cells. The inhibition of the Ras/MEK pathway restored the IFN-mediated
      induction of antiviral genes, indicating that activated Ras interrupts the IFN
      pathway upstream of antiviral gene transcription. Indeed, the IFN-induced
      phosphorylation of signal transducer and activator of transcription 1 (STAT1) and
      STAT2 was inhibited in RasV12 cells compared to that of vector control cells. In
      addition, we found that the total amount of STAT2 was reduced in RasV12 cells. To
      determine if the impaired IFN-alpha response can be rescued by restoring the
      overall level of STAT2, we overexpressed STAT2 in RasV12 cells. The IFN-alpha
      induced phosphorylation of STAT1 and STAT2, as well as the expression of
      antiviral protein, were restored, and IFN-induced antiviral protection was
      partially restored. Moreover, we demonstrated that the downregulation of STAT2
      levels by Ras/MEK was mediated at the transcriptional level. Thus, the activation
      of the Ras/MEK pathway reduces the amount of STAT2 available for propagating the
      IFN signal, resulting in the impairment of the IFN-alpha-induced antiviral
      response.

PMID- 19386710
TI  - Structure and expression strategy of the genome of Culex pipiens densovirus, a
      mosquito densovirus with an ambisense organization.
AB  - The genome of all densoviruses (DNVs) so far isolated from mosquitoes or mosquito
      cell lines consists of a 4-kb single-stranded DNA molecule with a monosense
      organization (genus Brevidensovirus, subfamily Densovirinae). We previously
      reported the isolation of a Culex pipiens DNV (CpDNV) that differs significantly
      from brevidensoviruses by (i) having a approximately 6-kb genome, (ii) lacking
      sequence homology, and (iii) lacking antigenic cross-reactivity with
      Brevidensovirus capsid polypeptides. We report here the sequence organization and
      transcription map of this virus. The cloned genome of CpDNV is 5,759 nucleotides
      (nt) long, and it possesses an inverted terminal repeat (ITR) of 285 nt and an
      ambisense organization of its genes. The nonstructural (NS) proteins NS-1, NS-2,
      and NS-3 are located in the 5' half of one strand and are organized into five
      open reading frames (ORFs) due to the split of both NS-1 and NS-2 into two ORFs.
      The ORF encoding capsid polypeptides is located in the 5' half of the
      complementary strand. The expression of NS proteins is controlled by two
      promoters, P7 and P17, driving the transcription of a 2.4-kb mRNA encoding NS-3
      and of a 1.8-kb mRNA encoding NS-1 and NS-2, respectively. The two NS mRNAs
      species are spliced off a 53-nt sequence. Capsid proteins are translated from an
      unspliced 2.3-kb mRNA driven by the P88 promoter. CpDNV thus appears as a new
      type of mosquito DNV, and based on the overall organization and expression
      modalities of its genome, it may represent the prototype of a new genus of DNV.

PMID- 19386712
TI  - Detection of nonstructural protein 6 in murine coronavirus-infected cells and
      analysis of the transmembrane topology by using bioinformatics and molecular
      approaches.
AB  - Coronaviruses encode large replicase polyproteins which are proteolytically
      processed by viral proteases to generate mature nonstructural proteins (nsps)
      that form the viral replication complex. Mouse hepatitis virus (MHV) replicase
      products nsp3, nsp4, and nsp6 are predicted to act as membrane anchors during
      assembly of the viral replication complexes. We report the first antibody
      mediated Western blot detection of nsp6 from MHV-infected cells. The nsp6
      specific peptide antiserum detected the replicase intermediate p150 (nsp4 to
      nsp11) and two nsp6 products of approximately 23 and 25 kDa. Analysis of nsp6
      transmembrane topology revealed six membrane-spanning segments and a conserved
      hydrophobic domain in the C-terminal cytosolic tail.

PMID- 19386711
TI  - Human papillomavirus type 16 (HPV-16) virus-like particle L1-specific CD8+
      cytotoxic T lymphocytes (CTLs) are equally effective as E7-specific CD8+ CTLs in
      killing autologous HPV-16-positive tumor cells in cervical cancer patients:
      implications for L1 dendritic cell-based therapeutic vaccines.
AB  - Papillomavirus-like particles (VLPs) based on L1 capsid protein represent a
      promising prophylactic vaccine against human papillomavirus (HPV) infections.
      However, cell-mediated immune responses against this antigen are believed to be
      of limited therapeutic value in established HPV-infected cervical lesions and,
      for this reason, have not been intensively investigated in cervical cancer
      patients. In this study we analyzed and quantified by real-time PCR (RT-PCR) the
      RNA expression levels of E6, E7, and L1 genes in flash-frozen HPV-16 cervical
      carcinomas. In addition, the kinetics of expression of E6, E7, and L1 in HPV-16
      infected primary cell lines established as long-term cultures in vitro was also
      evaluated at RNA and protein levels. Finally, in order to evaluate the
      therapeutic potential of L1-specific CD4(+) and CD8(+) T lymphocytes responses in
      cervical cancer patients, L1 VLP-loaded dendritic cells (DCs) were used to
      stimulate peripheral blood lymphocytes from cervical cancer patients and such
      responses were compared to those elicited by the E7 oncoprotein. We show that 22
      of 22 (100%) flash-frozen cervical biopsy samples collected from HPV-16-positive
      cervical cancer patients harbor L1, in addition to E6 and E7 RNA, as detected by
      RT-PCR. E7 RNA copy number (mean, 176.2) was significantly higher in HPV-16
      positive cervical cancers compared to the E6 RNA copy number (mean, 47.3) and the
      L1 copy number (mean, 58.3) (P < 0.0001 and P < 0.001, respectively). However, no
      significant differences in expression levels between E6 and L1 were found.
      Kinetic studies of E6, E7, and L1 RNA and protein expression levels in primary
      tumors showed a sharp reduction in L1 expression after multiple in vitro passages
      compared to E6 and E7. Autologous DCs pulsed with HPV-16 VLPs or recombinant full
      length E7 elicited strong type 1 L1- and E7-specific responses in CD4(+) and
      CD8(+) T cells from cervical cancer patients. Importantly, L1 VLP-specific CD8(+)
      T lymphocytes expressed strong cytolytic activity against autologous tumor cells
      and were as effective as E7-specific cytotoxic T lymphocytes in lysing naturally
      HPV-16-infected autologous tumor cells. Taken together, these data demonstrate a
      consistent expression of L1 in primary cervical tumors and the possibility of
      inducing effective L1/tumor-specific CD4(+) and CD8(+) T-lymphocyte responses in
      patients harboring HPV-infected cervical cancer. These results may have important
      implications for the treatment of patients harboring established HPV-infected
      lesions with L1 VLPs or combined E7/L1 DC-based vaccinations.

PMID- 19386713
TI  - Cassava brown streak virus (Potyviridae) encodes a putative Maf/HAM1
      pyrophosphatase implicated in reduction of mutations and a P1 proteinase that
      suppresses RNA silencing but contains no HC-Pro.
AB  - The complete positive-sense single-stranded RNA genome of Cassava brown streak
      virus (CBSV; genus Ipomovirus; Potyviridae) was found to consist of 9,069
      nucleotides and predicted to produce a polyprotein of 2,902 amino acids. It was
      lacking helper-component proteinase but contained a single P1 serine proteinase
      that strongly suppressed RNA silencing. Besides the exceptional structure of the
      5'-proximal part of the genome, CBSV also contained a Maf/HAM1-like sequence (678
      nucleotides, 226 amino acids) recombined between the replicase and coat protein
      domains in the 3'-proximal part of the genome, which is highly conserved in
      Potyviridae. HAM1 was flanked by consensus proteolytic cleavage sites for
      ipomovirus NIaPro cysteine proteinase. Homology of CBSV HAM1 with cellular
      Maf/HAM1 pyrophosphatases suggests that it may intercept noncanonical nucleoside
      triphosphates to reduce mutagenesis of viral RNA.

PMID- 19386714
TI  - Development of infectious clones for virulent and avirulent pichinde viruses: a
      model virus to study arenavirus-induced hemorrhagic fevers.
AB  - Several arenaviruses can cause hemorrhagic fever diseases (VHFs) in humans, the
      pathogenic mechanism of which is poorly understood due to their virulent nature
      and the lack of molecular clones. A safe, convenient, and economical small animal
      model of arenavirus hemorrhagic fever is based on guinea pigs infected by the
      arenavirus Pichinde (PICV). PICV does not cause disease in humans, but an adapted
      strain of PICV (P18) causes a disease in guinea pigs that mimics arenavirus
      hemorrhagic fever in humans in many aspects, while a low-passaged strain (P2)
      remains avirulent in infected animals. In order to identify the virulence
      determinants within the PICV genome, we developed the molecular clones for both
      the avirulent P2 and virulent P18 viruses. Recombinant viruses were generated by
      transfecting plasmids that contain the antigenomic L and S RNA segments of PICV
      under the control of the T7 promoter into BSRT7-5 cells, which constitutively
      express T7 RNA polymerase. By analyzing viral growth kinetics in vitro and
      virulence in vivo, we show that the recombinant viruses accurately recapitulate
      the replication and virulence natures of their respective parental viruses. Both
      parental and recombinant virulent viruses led to high levels of viremia and
      titers in different organs of the infected animals, whereas the avirulent viruses
      were effectively controlled and cleared by the hosts. These novel infectious
      clones for the PICV provide essential tools to identify the virulence factors
      that are responsible for the severe VHF-like disease in infected animals.

PMID- 19386715
TI  - Identification of varicella-zoster virus-specific CD8 T cells in patients after T
      cell-depleted allogeneic stem cell transplantation.
AB  - To study the role of CD8 T cells in the control of varicella-zoster virus (VZV)
      reactivation, we developed multimeric major histocompatibility complexes to
      identify VZV-specific CD8 T cells. Potential HLA-A2 binding peptides from the
      putative immediate-early 62 protein (IE62) of VZV were tested for binding, and
      peptides with sufficient binding capacity were used to generate pentamers.
      Patients with VZV reactivation following stem cell transplantation were screened
      with these pentamers, leading to the identification of the first validated class
      I-restricted epitope of VZV. In 42% of HLA-A2 patients following VZV
      reactivation, these IE62-ALW-A2 T cells could be detected ex vivo.

PMID- 19386716
TI  - Different subcellular localization of Theiler's murine encephalomyelitis virus
      leader proteins of GDVII and DA strains in BHK-21 cells.
AB  - The highly virulent GDVII strain of Theiler's murine encephalomyelitis virus
      causes acute and fatal encephalomyelitis, whereas the DA strain causes mild
      encephalomyelitis followed by a chronic inflammatory demyelinating disease with
      virus persistence. The differences in the amino acid sequences of the leader
      protein (L) of the DA and GDVII strains are greater than those for any other
      viral protein. We examined the subcellular distribution of DA L and GDVII L
      tagged with the FLAG epitope in BHK-21 cells. Wild-type GDVII L was localized
      predominantly in the cytoplasm, whereas wild-type DA L showed a nucleocytoplasmic
      distribution. A series of the L mutant experiments demonstrated that the zinc
      finger domain, acidic domain, and C-terminal region of L were necessary for the
      nuclear accumulation of DA L. A GDVII L mutant with a deletion of the
      serine/threonine (S/T)-rich domain showed a nucleocytoplasmic distribution, in
      contrast to the predominant cytoplasmic distribution of wild-type GDVII L. A
      chimeric DA/GDVII L, D/G, which encodes the N region of DA L including the zinc
      finger domain and acidic domain, followed by the GDVII L sequence including the
      S/T-rich domain, was distributed exclusively throughout the cytoplasm but not in
      the nucleus, as observed with wild-type GDVII L. Another chimeric L, G/D (which
      is the converse of the D/G construct), accumulated in the nucleus as well as the
      cytoplasm, as was observed for wild-type DA L. The findings suggest that the
      differential distribution of DA L and GDVII L is determined primarily by the S/T
      rich domain. The S/T-rich domain may be important for the viral activity through
      the regulation of the subcellular distribution of L.

PMID- 19386717
TI  - HLA class I subtype-dependent expansion of KIR3DS1+ and KIR3DL1+ NK cells during
      acute human immunodeficiency virus type 1 infection.
AB  - NK cells are critical in the early containment of viral infections.
      Epidemiological and functional studies have shown an important role of NK cells
      expressing specific killer immunoglobulin-like receptors (KIRs) in the control of
      human immunodeficiency virus type 1 (HIV-1) infection, but little is known about
      the mechanisms that determine the expansion of these antiviral NK cell
      populations during acute HIV-1 infection. Here we demonstrate that NK cells
      expressing the activating receptor KIR3DS1(+) and, to a lesser extent, the
      inhibitory receptor KIR3DL1(+) specifically expand in acute HIV-1 infection in
      the presence of HLA-B Bw480I, the putative HLA class I ligand for KIR3DL1/3DS1.
      These data demonstrate for the first time the HLA class I subtype-dependent
      expansion of specific KIR(+) NK cells during an acute viral infection in humans.

PMID- 19386718
TI  - Identification of infected B-cell populations by using a recombinant murine
      gammaherpesvirus 68 expressing a fluorescent protein.
AB  - Infection of inbred mice with murine gammaherpesvirus 68 (MHV68) has proven to be
      a powerful tool to study gammaherpesvirus pathogenesis. However, one of the
      limitations of this system has been the inability to directly detect infected
      cells harvested from infected animals. To address this issue, we generated a
      transgenic virus that expresses the enhanced yellow fluorescent protein (YFP),
      driven by the human cytomegalovirus immediate-early promoter and enhancer, from a
      neutral locus within the viral genome. This virus, MHV68-YFP, replicated and
      established latency as efficiently as did the wild-type virus. During the early
      phase of viral latency, MHV68-YFP efficiently marked latently infected cells in
      the spleen after intranasal inoculation. Staining splenocytes for expression of
      various surface markers demonstrated the presence of MHV68 in distinct
      populations of splenic B cells harboring MHV68. Notably, these analyses also
      revealed that markers used to discriminate between newly formed, follicular and
      marginal zone B cells may not be reliable for phenotyping B cells harboring MHV68
      since virus infection appears to modulate cell surface expression levels of CD21
      and CD23. However, as expected, we observed that the overwhelming majority of
      latently infected B cells at the peak of latency exhibited a germinal center
      phenotype. These analyses also demonstrated that a significant percentage of
      MHV68-infected splenocytes at the peak of viral latency are plasma cells (ca. 15%
      at day 14 and ca. 8% at day 18). Notably, the frequency of virus-infected plasma
      cells correlated well with the frequency of splenocytes that spontaneously
      reactivate virus upon explant. Finally, we observed that the efficiency of
      marking latently infected B cells with the MHV68-YFP recombinant virus declined
      at later times postinfection, likely due to shut down of transgene expression,
      and indicating that the utility of this marking strategy is currently limited to
      the early stages of virus infection.

PMID- 19386719
TI  - Effective downregulation of HLA-A*2 and HLA-B*57 by primary human
      immunodeficiency virus type 1 isolates cultured from elite suppressors.
AB  - Elite controllers or suppressors (ES) are human immunodeficiency virus type 1
      (HIV-1)-infected patients who control viral replication to <50 copies/ml without
      antiretroviral therapy. Downregulation of HLA class I molecules is an important
      mechanism used by HIV-1 to evade the immune system. In this study, we showed that
      primary isolates from ES are as effective as isolates obtained from patients with
      progressive HIV-1 disease at downregulating HLA-A*2 and HLA-B*57 molecules on
      primary CD4(+) T cells. Thus, a diminished ability of viral isolates from ES to
      evade HIV-specific immune responses probably does not contribute to the control
      of viral replication in these patients.

PMID- 19386720
TI  - Homologous recombinational repair factors are recruited and loaded onto the viral
      DNA genome in Epstein-Barr virus replication compartments.
AB  - Homologous recombination is an important biological process that facilitates
      genome rearrangement and repair of DNA double-strand breaks (DSBs). The induction
      of Epstein-Barr virus (EBV) lytic replication induces ataxia telangiectasia
      mutated (ATM)-dependent DNA damage checkpoint signaling, leading to the
      clustering of phosphorylated ATM and Mre11/Rad50/Nbs1 (MRN) complexes to sites of
      viral genome synthesis in nuclei. Here we report that homologous recombinational
      repair (HRR) factors such as replication protein A (RPA), Rad51, and Rad52 as
      well as MRN complexes are recruited and loaded onto the newly synthesized viral
      genome in replication compartments. The 32-kDa subunit of RPA is extensively
      phosphorylated at sites in accordance with those with ATM. The
      hyperphosphorylation of RPA32 causes a change in RPA conformation, resulting in a
      switch from the catalysis of DNA replication to the participation in DNA repair.
      The levels of Rad51 and phosphorylated RPA were found to increase with the
      progression of viral productive replication, while that of Rad52 proved constant.
      Furthermore, biochemical fractionation revealed increases in levels of DNA-bound
      forms of these HRRs. Bromodeoxyuridine-labeled chromatin immunoprecipitation and
      PCR analyses confirmed the loading of RPA, Rad 51, Rad52, and Mre11 onto newly
      synthesized viral DNA, and terminal deoxynucleotidyltransferase-mediated dUTP
      nick end labeling analysis demonstrated DSBs in the EBV replication compartments.
      HRR factors might be recruited to repair DSBs on the viral genome in viral
      replication compartments. RNA interference knockdown of RPA32 and Rad51 prevented
      viral DNA synthesis remarkably, suggesting that homologous recombination and/or
      repair of viral DNA genome might occur, coupled with DNA replication to
      facilitate viral genome synthesis.

PMID- 19386721
TI  - Determinants of secretion and intracellular localization of human herpesvirus 8
      interleukin-6.
AB  - Human herpesvirus 8 (HHV-8) interleukin-6 (vIL-6) is distinct from human and
      other cellular IL-6 proteins in that it does not require the nonsignaling alpha
      receptor subunit for the formation of gp130-based signal transducing complexes
      and also is largely retained intracellularly rather than being secreted. We and
      others have reported that vIL-6 is retained and is active in the endoplasmic
      reticulum (ER) compartment, and data from our laboratory have demonstrated that
      intracellular vIL-6 is functional in the autocrine promotion of proliferation and
      survival of HHV-8 latently infected primary effusion lymphoma cells. It has also
      been reported that vIL-6 secretion in gp130-deficient cells can be enhanced by
      introduced gp130, thereby implicating the signal transducer in vIL-6 trafficking
      to the cell surface. We examine here the requirements for intracellular retention
      and localization of vIL-6. Using vIL-6-hIL-6 chimeric and point-mutated vIL-6
      proteins, we identified regions and residues of vIL-6 influencing vIL-6
      secretion. However, there was no correlation between vIL-6 secretion and gp130
      interaction. We found that vIL-6, but not hIL-6, could associate stably with ER
      resident chaperone protein calnexin. Glycosylation-dependent interaction of vIL-6
      with calnexin correlated with proper protein folding, but there was no direct
      relationship between vIL-6-calnexin interaction and intracellular retention.
      While calnexin depletion had little influence on absolute amounts of secreted vIL
      6, it led to markedly reduced levels of intracellular cytokine. This was reversed
      by gp130 transduction, which had no detectable effect on vIL-6 secretion, but
      redistributed vIL-6 into ER-distinct locations in calnexin-depleted cells,
      specifically. Our data reveal that calnexin plays a role in ER localization of
      vIL-6 and that gp130 promotes ER exit, but not secretion, of the viral cytokine.

PMID- 19386722
TI  - Activation of the PI3K/Akt pathway early during vaccinia and cowpox virus
      infections is required for both host survival and viral replication.
AB  - Viral manipulation of the transduction pathways associated with key cellular
      functions such as actin remodeling, microtubule stabilization, and survival may
      favor a productive viral infection. Here we show that consistent with the
      vaccinia virus (VACV) and cowpox virus (CPXV) requirement for cytoskeleton
      alterations early during the infection cycle, PBK/Akt was phosphorylated at S473
      [Akt(S473-P)], a modification associated with the mammalian target of rapamycin
      complex 2 (mTORC2), which was paralleled by phosphorylation at T308 [Akt(T308-P)]
      by PI3K/PDK1, which is required for host survival. Notably, while VACV stimulated
      Akt(S473-P/T308-P) at early (1 h postinfection [p.i.]) and late (24 h p.i.) times
      during the infective cycle, CPXV stimulated Akt at early times only.
      Pharmacological and genetic inhibition of PI3K (LY294002) or Akt (Akt-X and a
      dominant-negative form of Akt-K179M) resulted in a significant decline in virus
      yield (from 80% to >/=90%). This decline was secondary to the inhibition of late
      viral gene expression, which in turn led to an arrest of virion morphogenesis at
      the immature-virion stage of the viral growth cycle. Furthermore, the cleavage of
      both caspase-3 and poly(ADP-ribose) polymerase and terminal deoxynucleotidyl
      transferase-mediated deoxyuridine nick end labeling assays confirmed that
      permissive, spontaneously immortalized cells such as A31 cells and mouse
      embryonic fibroblasts (MEFs) underwent apoptosis upon orthopoxvirus infection
      plus LY294002 treatment. Thus, in A31 cells and MEFs, early viral receptor
      mediated signals transmitted via the PI3K/Akt pathway are required and precede
      the expression of viral antiapoptotic genes. Additionally, the inhibition of
      these signals resulted in the apoptosis of the infected cells and a significant
      decline in viral titers.

PMID- 19386724
TI  - Basic fibroblast growth factor causes urinary bladder overactivity through gap
      junction generation in the smooth muscle.
AB  - Overactive bladder is a highly prevalent clinical condition that is often caused
      by bladder outlet obstruction (BOO). Increased coupling of bladder smooth muscle
      cells (BSMC) via gap junctions has been hypothesized as a mechanism for myogenic
      bladder overactivity in BOO, although little is known about the regulatory system
      underlying such changes. Here, we report the involvement of basic fibroblast
      growth factor (bFGF) and connexin 43, a bladder gap junction protein, in bladder
      overactivity. BOO created by urethral constriction in rats resulted in elevated
      bFGF and connexin 43 levels in the bladder urothelium and muscle layer,
      respectively, and muscle strips from these bladders were more sensitive than
      those from sham-operated controls to a cholinergic agonist. In vitro bFGF
      treatment increased connexin 43 expression in cultured rat BSMC via the ERK 1/2
      pathway. This finding was supported by another in vivo model, where bFGF released
      from gelatin hydrogels fixed on rat bladder walls caused connexin 43 upregulation
      and gap junction formation in the muscle layer. Bladder muscle strips in this
      model showed increased sensitivity to a cholinergic agonist that was blocked by
      inhibition of gap junction function with alpha-glycyrrhetinic acid. Cystometric
      analyses of this model showed typical features of detrusor overactivity such as
      significantly increased micturition frequency and decreased bladder capacity.
      These findings suggest that bFGF from the urothelium could induce bladder
      hypersensitivity to acetylcholine via gap junction generation in the smooth
      muscle, thereby contributing to the myogenic overactivity of obstructed bladders.

PMID- 19386723
TI  - Expression and modulation of translocator protein and its partners by hypoxia
      reoxygenation or ischemia and reperfusion in porcine renal models.
AB  - Translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine
      receptor, is an 18-kDa drug- and cholesterol-binding protein localized to the
      outer mitochondrial membrane and implicated in a variety of cell and
      mitochondrial functions. To determine the role of TSPO in ischemia-reperfusion
      injury (IRI), we used both in vivo and in vitro porcine models: an in vivo renal
      ischemia model where different conservation modalities were tested and an in
      vitro model where TSPO-transfected porcine proximal tubule LLC-PK(1) cells were
      exposed to hypoxia and oxidative stress. The expression of TSPO and its partners
      in steroidogenic cells, steroidogenic acute regulatory protein (StAR) and
      cytochrome P-450 side chain cleavage CYP11A1, as well as the impact of TSPO
      overexpression and exposure to TSPO ligands in vitro in hypoxia-ischemia
      conditions were investigated. Hypoxia induced caspase activation, reduction of
      ATP content, and LLC-PK(1) cell death. Transfection and overexpression of TSPO
      rescued the cells from the detrimental effects of hypoxia and reoxygenation.
      Moreover, TSPO overexpression was accompanied by a reduction of H(2)O(2)-induced
      necrosis. TSPO drug ligands did not affect TSPO-mediated functions. In vivo, TSPO
      expression was modulated by IRI and during regeneration particularly in proximal
      tubule cells, which do not express this protein at the basal level. Under the
      same conditions, StAR and CYP11A1 protein and gene expression was reduced without
      apparent relation to TSPO changes. Pregnenolone was identified and measured in
      the pig kidney. Pregnenolone synthesis was not affected by the experimental
      conditions used. Taken together, these results indicate that changes in TSPO
      expression in kidney regenerating tissue could be important for renal protection
      and maintenance of kidney function.

PMID- 19386725
TI  - AT(1) receptor activation regulates the mRNA expression of CAT1, CAT2, arginase
      1, and DDAH2 in preglomerular vessels from angiotensin II hypertensive rats.
AB  - Previously, we found increased expression of l-arginine metabolizing enzymes in
      both kidneys from two-kidney, one-clip (2K1C) hypertensive rats (Helle F,
      Hultstrom M, Skogstrand T, Palm F, Iversen BM. Am J Physiol Renal Physiol 296:
      F78-F86, 2009). In the present study, we investigate whether AT(1) receptor
      activation can induce the changes observed in 2K1C. Four groups of rats were
      infused with 80 ng/min ANG II or saline for 14 days and/or given 60 mg x kg(-1) x
      day(-1) losartan. Gene expression was studied in isolated preglomerular vessels
      by RT-PCR. Dose-responses to ANG II were studied in isolated preglomerular
      vessels with and without acute NOS inhibition [10(-4) mol/l N(G)-nitro-l-arginine
      methyl ester (l-NAME)]. Expressions of endothelial nitric oxide synthase (eNOS),
      caveolin-1, and arginase-2 were not changed by ANG II infusion. CAT1 (0.3 8 +/-
      0.07 to 0.73 +/- 0.12, P < 0.05), CAT2 (1.14 +/- 0.29 to 2.74 +/- 0.48), DDAH2
      (1.09 +/- 0.27 to 2.3 +/- 0.46), and arginase-1 (1.08 +/- 0.17 to 1.82 +/- 0.22)
      were increased in ANG II-infused rats. This was prevented by losartan treatment,
      which reduced the expression of eNOS (0.97 +/- 0.26 to 0.37 +/- 0.11 in controls;
      0.8 +/- 0.16 to 0.36 +/- 0.1 in ANG II-infused rats) and caveolin-1 (2.49 +/-
      0.59 to 0.82 +/- 0.24 in controls and 2.59 +/- 0.61 to 1.1 +/- 0.25 in ANG II
      infused rats). ANG II (10(-10) mol/l) caused vessels from ANG II-infused animals
      to contract to 53 +/- 15% of baseline diameter and 90 +/- 5% of baseline diameter
      in controls (P < 0.05) and was further enhanced by l-NAME to 4 +/- 4% of baseline
      diameter (P < 0.05). In vivo losartan treatment reduced the reactivity of
      isolated vessels to 91 +/- 2% of baseline in response to 10(-7) mol/l ANG II
      compared with 82 +/- 3% in controls (P < 0.05) and prevented the increased
      responsiveness caused by ANG II infusion. In conclusion, CAT1, CAT2, DDAH2, and
      arginase-1 expression in renal resistance vessels is regulated through the AT(1)
      receptor. This finding may be of direct importance for NOS and the regulation of
      preglomerular vascular function.

PMID- 19386726
TI  - Accuracy modulating mutations of the ribosomal protein S4-S5 interface do not
      necessarily destabilize the rps4-rps5 protein-protein interaction.
AB  - During the process of translation, an aminoacyl tRNA is selected in the A site of
      the decoding center of the small subunit based on the correct codon-anticodon
      base pairing. Though selection is usually accurate, mutations in the ribosomal
      RNA and proteins and the presence of some antibiotics like streptomycin alter
      translational accuracy. Recent crystallographic structures of the ribosome
      suggest that cognate tRNAs induce a "closed conformation" of the small subunit
      that stabilizes the codon-anticodon interactions at the A site. During formation
      of the closed conformation, the protein interface between rpS4 and rpS5 is broken
      while new contacts form with rpS12. Mutations in rpS12 confer streptomycin
      resistance or dependence and show a hyperaccurate phenotype. Mutations reversing
      streptomycin dependence affect rpS4 and rpS5. The canonical rpS4 and rpS5
      streptomycin independent mutations increase translational errors and were called
      ribosomal ambiguity mutations (ram). The mutations in these proteins are proposed
      to affect formation of the closed complex by breaking the rpS4-rpS5 interface,
      which reduces the cost of domain closure and thus increases translational errors.
      We used a yeast two-hybrid system to study the interactions between the small
      subunit ribosomal proteins rpS4 and rpS5 and to test the effect of ram mutations
      on the stability of the interface. We found no correlation between ram phenotype
      and disruption of the interface.

PMID- 19386727
TI  - Endovascular approaches to acute stroke, part 2: a comprehensive review of
      studies and trials.
AB  - Reperfusion remains the mainstay of acute ischemic stroke treatment. Endovascular
      therapy has become a promising alternative for patients who are ineligible for or
      have failed intravenous (IV) thrombolysis. The conviction that recanalization of
      properly selected patients is essential for the achievement of good clinical
      outcomes has led to the rapid and widespread growth in the adoption of
      endovascular stroke therapies. However, comparisons of the recent reperfusion
      studies have brought into question the strength of the association between
      revascularization and improved clinical outcome. Despite higher rates of
      recanalization, the mechanical thrombectomy studies have demonstrated
      substantially lower rates of good outcomes compared with IV and/or intra-arterial
      thrombolytic trials. However, such analyses disregard important differences in
      clot location and burden, baseline stroke severity, time from stroke onset to
      treatment, and patient selection in these studies. Many clinical trials are
      testing novel devices and drugs as well as the paradigm of physiology-based
      stroke imaging as a treatment-selection tool. The objective of this article is to
      provide a comprehensive review of the relevant past, current, and upcoming data
      on endovascular stroke therapy with a special focus on the prospective studies
      and randomized clinical trials.

PMID- 19386728
TI  - CT and MR imaging cochlear distance measurements may predict cochlear implant
      length required for a 360 degrees insertion.
AB  - BACKGROUND AND PURPOSE: A preoperative prediction of the 360 degrees point
      insertion depth would aid the planning of electric acoustic stimulation (EAS)
      implantation. The purpose of this study was to establish whether the distance
      between the round window and the opposite cochlear wall on CT or MR imaging may
      be used to predict the length of a cochlear implant electrode array required to
      be inserted to the 360 degrees point of the basal turn. MATERIALS AND METHODS: CT
      and MR imaging data were studied in 19 patients undergoing cochlear implantation.
      Distances were measured between the round window and the opposite outer cochlear
      wall on an oblique paracoronal reformatted image. Adjusted distance measurements
      were applied to a spiral function to estimate the length of an electrode array
      extending between the round window entry point and the 360 degrees point. This
      was compared with measurements of implant length to this insertion depth on
      postoperative CT. RESULTS: Intraobserver reproducibility for each of the 2
      observers was r = 0.85/0.55 for CT and r = 0.87/0.67 for MR imaging.
      Interobserver reproducibility was r = 0.68 for CT and r = 0.84 for MR imaging.
      There was no bias between CT and MR imaging measurements, with a mean difference
      of less than 0.1 mm. CT and MR imaging estimates markedly correlated with the
      actual length of the electrode array extending to the 360 degrees insertion depth
      (SD between the estimated and actual length was 0.84 mm for CT and 0.87 mm for MR
      imaging). CONCLUSIONS: CT and MR imaging measures of cochlear distance (CD) were
      used to predict insertion depths to 360 degrees , and these were markedly
      concordant with the actual length of the electrode array required to reach this
      point. MR imaging measurements were more precise and similar in accuracy to those
      obtained with CT.

PMID- 19386729
TI  - Volume-based morphometry of brain MR images in adolescent idiopathic scoliosis
      and healthy control subjects.
AB  - BACKGROUND AND PURPOSE: Adolescent idiopathic scoliosis (AIS) is a spinal
      deformity with unknown cause. Previous studies have suggested that subclinical
      neurologic abnormalities are associated with AIS. The objective of this
      prospective study was to characterize systematically neuroanatomic changes in
      patients with left thoracic AIS vs right thoracic AIS and healthy control
      subjects by using volume-based morphometry. MATERIALS AND METHODS: Our current
      study involved 9 girls with left thoracic AIS and 20 girls with right thoracic
      AIS vs 11 and 17 matched female control subjects, respectively. Voxel-based
      morphometry (VBM), deformation-based morphometry (DBM), and tensor-based
      morphometry (TBM) were used to analyze the MR images aligned with a specific
      brain template of local adolescent girls. The statistical t test was used in VBM
      and TBM, and the Hotelling T(2) test was applied in DBM. RESULTS: Using VBM, we
      found statistically significant differences (P < .05) in the white matter
      attenuation of the genu of the corpus callosum and left internal capsule (left
      thoracic AIS < control subjects). In contrast, no significant differences were
      observed between patients with right thoracic AIS and control subjects.
      CONCLUSIONS: White matter attenuation in the corpus callosum and left internal
      capsule, responsible for interhemispheric communication and conduit of the
      corticothalamic projectional fibers, respectively, were found to be significantly
      lower in left thoracic AIS compared with control subjects; however, this was not
      the case in right thoracic AIS. Confirmation of the findings is required in
      future research, which needs to evaluate the relationship of white matter
      abnormality to curve laterality, pathogenesis, and prognosis in patients with
      AIS, with biologic significance and possible therapeutic correction.

PMID- 19386730
TI  - A limbic encephalitis MR imaging in a patient with Behcet disease and relapsing
      polychondritis.

PMID- 19386731
TI  - Hemorrhage in posterior reversible encephalopathy syndrome: imaging and clinical
      features.
AB  - BACKGROUND AND PURPOSE: Hemorrhage is known to occur in posterior reversible
      encephalopathy syndrome (PRES), but the characteristics have not been analyzed in
      detail. The purpose of this study was to evaluate the imaging and clinical
      features of hemorrhage in PRES. MATERIALS AND METHODS: Retrospective assessment
      of 151 patients with PRES was performed, and 23 patients were identified who had
      intracranial hemorrhage at toxicity. Hemorrhage types were identified and
      tabulated, including minute focal hemorrhages (<5 mm), sulcal subarachnoid
      hemorrhage, and focal hematoma. Clinical features of hemorrhage and nonhemorrhage
      PRES groups were evaluated, including toxicity blood pressure, coagulation
      profile/platelet counts, coagulation-altering medication, and clinical conditions
      associated with PRES. Toxicity mean arterial pressure (MAP) groups were defined
      as normal (<106 mm Hg), mildly hypertensive (106-116 mm Hg), or severely
      hypertensive (>116 mm Hg). RESULTS: The overall incidence of hemorrhage was
      15.2%, with borderline statistical significance noted between the observed
      clinical associations (P = .07). Hemorrhage was significantly more common (P =
      .02) after allogeneic bone marrow transplantation (allo-BMT) than after solid
      organ transplantation. The 3 hemorrhage types were noted with equal frequency. A
      single hemorrhage type was found in 16 patients, with multiple types noted in 7.
      Patients undergoing therapeutic anticoagulation were statistically more likely to
      develop hemorrhage (P = .04). No difference in hemorrhage incidence was found
      among the 3 blood pressure subgroups (range, 14.9%-15.9%). CONCLUSIONS: Three
      distinct types of hemorrhage (minute hemorrhage, sulcal subarachnoid hemorrhage,
      hematoma) were identified in PRES with equal frequency. The greatest hemorrhage
      frequency was seen after allo-BMT and in patients undergoing therapeutic
      anticoagulation. Hemorrhage rate was independent of the toxicity blood pressure.

PMID- 19386733
TI  - Neck injury is critical to elastase-induced aneurysm model.
AB  - We modified the elastase-induced aneurysm model by use of a simple surgical
      technique in rabbits. A temporary arcuated aneurysm clip was placed at the origin
      of the right common carotid artery (RCCA), ascertaining the inner edge of the
      clip blade on the juncture of the RCCA and right subclavian artery (RSCA), and
      the elastase-induced aneurysm procedure was undertaken. We found elastase and
      location of the temporary arcuated aneurysm clip are critical to the success of
      this aneurysm model.

PMID- 19386734
TI  - Consider using diffusion tensor imaging in Geron phase I trial.

PMID- 19386732
TI  - Diffusion tensor imaging detects abnormalities in the corticospinal tracts of
      neonates with infantile Krabbe disease.
AB  - BACKGROUND AND PURPOSE: It is not possible to determine if neonates diagnosed
      with Krabbe disease through statewide neonate screening programs will develop the
      disease as infants, juveniles, or adults. The only available treatment for this
      fatal neurodegenerative condition is unrelated umbilical cord transplantation,
      but this treatment is only effective before clinical symptoms appear. Therefore,
      a marker of disease progression is needed. The purpose of this study was to
      evaluate the use of diffusion tensor imaging (DTI) with fiber tracking in
      identifying early changes in major motor tracts of asymptomatic neonates with
      infantile Krabbe disease. MATERIALS AND METHODS: Six neonates with infantile
      Krabbe disease identified because of family history underwent brain MR imaging
      within the first 4 weeks of life. Six-direction DTI and quantitative tractography
      of the corticospinal tracts were performed. Hypothesis tests, 1 for each
      hemisphere, were used to determine whether the fractional anisotropy (FA) ratio
      of the neonates with infantile Krabbe disease was significantly different from
      that of 45 age- and sex-matched controls. RESULTS: The average FA ratio for
      patients with Krabbe disease was 0.89 and 0.87 for left and right tracts,
      respectively (P = .002 and < .001). After adjusting for gestational age,
      gestational age at birth, birth weight, sex, and race, the 6 patients with Krabbe
      disease had significantly lower FA values than the controls (P < .001).
      CONCLUSIONS: DTI with quantitative tractography detected significant differences
      in the corticospinal tracts of asymptomatic neonates who had the early-onset form
      of Krabbe disease. Once standardized and validated, this tool has the potential
      to be used as a marker of disease progression in neonates diagnosed through
      statewide neonate screening programs.

PMID- 19386735
TI  - A cherubism with aneurysmal bone cyst.

PMID- 19386736
TI  - Scoring clinical functions in subacute sclerosing panencephalitis.

PMID- 19386737
TI  - Functional imaging of central nervous system involvement in complex regional pain
      syndrome.
AB  - SUMMARY: In complex regional pain syndrome (CRPS), functional imaging studies
      gave evidence for an important role of the central nervous system (CNS) in the
      pathogenesis of the disease. Especially, reorganization in central somatosensory
      and motor networks was demonstrated, leading to an altered central processing of
      tactile and nociceptive stimuli, as well as to an altered cerebral organization
      of movement. These findings may explain a number of clinical signs and symptoms
      occurring in the course of the disease and seem to be closely related to chronic
      pain in CRPS. Neurorehabilitative strategies, which target cortical areas and aim
      to restore impaired sensorimotor function in patients with CRPS, therefore, may
      be effective not only in restoring impaired function but also in pain reduction.
      This article reviews findings of functional imaging studies, which have been
      conducted to clarify CNS involvement in the course of CRPS.

PMID- 19386738
TI  - Body iron excretion by healthy men and women.
AB  - BACKGROUND: Iron excretion measured by isotope dilution has been a primary basis
      for the factorial derivation of recommendations for iron intake, but the results
      have been available for men only. OBJECTIVE: The objective of this study was to
      confirm iron excretion measurements in healthy men and extend them to women.
      DESIGN: The turnover rate of 55Fe that had been administered > or =1 y earlier
      was determined from blood sampled semiannually for up to 3 y from 53 subjects in
      the community. Body iron was determined from hemoglobin, serum ferritin, and
      transferrin receptor. Complete menstrual collections were obtained from 13 women.
      RESULTS: The total median (range) iron excretion was 1.18 (0.11-2.07) mg/d for 29
      men, 1.58 (0.65-4.88) mg/d for 19 menstruating women, and 0.99 (0.86-1.57) for 5
      postmenopausal women. When hormonal contraceptive users were omitted, the median
      for 15 menstruating women increased to 1.66 mg/d. The distribution of iron
      excretion was normal for the men and postmenopausal women and was highly skewed
      for the menstruating women; menstrual iron accounted for 90% of the variation.
      Iron excretion was not strongly related to body weight. Body iron in menstruating
      women decreased somewhat (by 4.6%) in the men and tended to increase (by 1.5%)
      during the study. CONCLUSIONS: The results extend direct iron excretion
      measurements in men to include similar measurements in women. The results
      emphasize the wide range of iron excretion in humans, which results in a 40-fold
      range of requirements for absorbed iron. This trial was registered at
      clinicaltrials.gov as NCT00755105.

PMID- 19386739
TI  - Leukocyte telomere length: the telomere tale continues.

PMID- 19386740
TI  - Effect of dietary macronutrient composition under moderate hypocaloric intake on
      maternal adaptation during lactation.
AB  - BACKGROUND: No evidence-based recommendations exist concerning what dietary
      macronutrient composition optimizes weight loss during lactation while
      maintaining milk production. OBJECTIVES: The study was designed to test the
      following hypotheses: compared with a reduced-calorie, high-carbohydrate (H-CHO)
      diet, an isonitrogenous, isocaloric high-fat (H-F) diet will decrease milk
      production and carbohydrate oxidation, increase gluconeogenesis and
      hexoneogenesis, and not affect energy balance. DESIGN: Seven healthy lactating
      mothers and their infants were studied on 2 occasions in random order for 8 d
      separated by 1-2 wk. On one occasion, the subjects received the H-F (30% of
      energy as carbohydrate and 55% as fat) diet and on the other occasion received
      the H-CHO (60% of energy as carbohydrate and 25% as fat) diet. Milk production,
      infant intakes, and substrate and hormone concentrations were measured. Glucose
      rates of appearance, production, gluconeogenesis, glycogenolysis, and
      hexoneogenesis were measured by using stable-isotope gas chromatography-mass
      spectrometric techniques, and energy expenditure and substrate oxidation were
      measured by using indirect calorimetry. RESULTS: Milk volume, lactose, and
      protein concentrations were unaffected. Milk fat, energy, and infant intakes were
      higher (P < 0.05) during the H-F diet. Neither gluconeogenesis nor hexoneogenesis
      was different. During the H-F diet, energy expenditure and fat and protein
      oxidation rates were higher (P < 0.05), and the daily energy balance deficit was
      greater (P < 0.01). CONCLUSIONS: Milk fat, energy output, and energy expenditure
      were higher during the H-F diet, which resulted in a greater negative energy
      balance. The lactating mothers adapted to a low carbohydrate intake by decreasing
      carbohydrate oxidation. Additional studies are warranted to determine whether a
      hypocaloric H-F diet might promote weight loss to a greater extent than the H-CHO
      diet while maintaining milk production.

PMID- 19386741
TI  - Weight loss during oligofructose supplementation is associated with decreased
      ghrelin and increased peptide YY in overweight and obese adults.
AB  - BACKGROUND: Rodent studies show that oligofructose promotes weight loss,
      stimulates satiety hormone secretion, reduces energy intake, and improves lipid
      profiles. OBJECTIVE: Our objective was to examine the effects of oligofructose
      supplementation on body weight and satiety hormone concentrations in overweight
      and obese adults. DESIGN: This study was a randomized, double-blind, placebo
      controlled trial. Forty-eight otherwise healthy adults with a body mass index (in
      kg/m2) > 25 were randomly assigned to receive 21 g oligofructose/d or a placebo
      (maltodextrin) for 12 wk. Body composition (by dual-energy X-ray absorptiometry);
      meal tolerance tests, including satiety hormone response; food intake; and
      subjective appetite ratings were determined. RESULTS: There was a reduction in
      body weight of 1.03 +/- 0.43 kg with oligofructose supplementation, whereas the
      control group experienced an increase in body weight of 0.45 +/- 0.31 kg over 12
      wk (P = 0.01). A lower area under the curve (AUC) for ghrelin (P = 0.004) and a
      higher AUC for peptide YY (PYY) with oligofructose (P = 0.03) coincided with a
      reduction in self-reported caloric intake (P < or = 0.05). Glucose decreased in
      the oligofructose group and increased in the control group between initial and
      final tests (P < or = 0.05). Insulin concentrations mirrored this pattern (P < or
      = 0.05). Oligofructose supplementation did not affect plasma active glucagon-like
      peptide 1 secretion. According to a visual analog scale designed to assess side
      effects, oligofructose was well tolerated. CONCLUSIONS: Independent of other
      lifestyle changes, oligofructose supplementation has the potential to promote
      weight loss and improve glucose regulation in overweight adults. Suppressed
      ghrelin and enhanced PYY may contribute in part to the reduction in energy
      intake. The trial was registered at clinicaltrials.gov as NCT00522353.

PMID- 19386742
TI  - Optimal protein intake in healthy infants.

PMID- 19386743
TI  - Lipid profiles in middle-aged men and women after famine exposure during
      gestation: the Dutch Hunger Winter Families Study.
AB  - BACKGROUND: Many studies in humans have related birth weight to lipid profiles in
      adulthood. Fewer have estimated associations directly attributable to maternal
      nutrition during pregnancy. OBJECTIVE: Our objective was to determine whether
      famine exposure during gestation is associated with a more atherogenic profile in
      adult offspring. DESIGN: In 2003-2005, we studied 1) 359 singleton men and women
      born between January 1945 and March 1946 in clinics in Amsterdam, Rotterdam, and
      Leiden whose mothers were exposed to the famine during pregnancy; 2) 299
      singletons born in the same 3 institutions during 1943 or 1947; and 3) 313
      unexposed same-sex siblings of the above individuals. A lipid profile was
      obtained after an overnight fast. RESULTS: Female offspring with prenatal famine
      exposure had a dyslipidemic pattern characterized by elevated total cholesterol
      (0.26 mmol/L; 95% CI: 0.07, 0.46; P = 0.007), triglycerides (0.17 mmol/L; 95% CI:
      0.03, 0.31; P = 0.02), and LDL cholesterol (0.17 mmol/L; 95% CI: -0.01, 0.36; P =
      0.06) compared with unexposed offspring. This pattern was not seen in men. The
      increases in total cholesterol and LDL cholesterol were independent of body mass
      index, waist circumference, and midthigh circumference. The increase in
      triglycerides was independent of midthigh circumference but was attenuated with
      control for either body mass index or waist circumference. There was no evidence
      for associations within specific gestational windows. No association was observed
      between prenatal famine exposure and HDL cholesterol in either sex. CONCLUSION:
      In women, but not in men, aged approximately 58 y, we observed an association
      between prenatal undernutrition and elevated total cholesterol concentrations and
      triglycerides.

PMID- 19386744
TI  - Vitamin K supplementation and progression of coronary artery calcium in older men
      and women.
AB  - BACKGROUND: Coronary artery calcification (CAC) is an independent predictor of
      cardiovascular disease. A preventive role for vitamin K in CAC progression has
      been proposed on the basis of the properties of matrix Gla protein (MGP) as a
      vitamin K-dependent calcification inhibitor. OBJECTIVE: The objective was to
      determine the effect of phylloquinone (vitamin K1) supplementation on CAC
      progression in older men and women. DESIGN: CAC was measured at baseline and
      after 3 y of follow-up in 388 healthy men and postmenopausal women; 200 received
      a multivitamin with 500 microg phylloquinone/d (treatment), and 188 received a
      multivitamin alone (control). RESULTS: In an intention-to-treat analysis, there
      was no difference in CAC progression between the phylloquinone group and the
      control group; the mean (+/-SEM) changes in Agatston scores were 27 +/- 6 and 37
      +/- 7, respectively. In a subgroup analysis of participants who were > or =85%
      adherent to supplementation (n = 367), there was less CAC progression in the
      phylloquinone group than in the control group (P = 0.03). Of those with
      preexisting CAC (Agatston score > 10), those who received phylloquinone
      supplements had 6% less progression than did those who received the multivitamin
      alone (P = 0.04). Phylloquinone-associated decreases in CAC progression were
      independent of changes in serum MGP. MGP carboxylation status was not determined.
      CONCLUSIONS: Phylloquinone supplementation slows the progression of CAC in
      healthy older adults with preexisting CAC, independent of its effect on total MGP
      concentrations. Because our data are hypothesis-generating, further studies are
      warranted to clarify this mechanism. This trial was registered at
      clinicaltrials.gov as NCT00183001.

PMID- 19386745
TI  - Is higher sodium intake associated with elevated systemic inflammation? A
      population-based study.
AB  - BACKGROUND: Observational epidemiologic studies have suggested that a low-sodium
      diet is associated with reduced mortality. OBJECTIVE: The objective was to test
      the hypothesis that a higher dietary intake of sodium is associated with
      increased systemic inflammation--a potential risk factor for both cardiovascular
      disease and cancer. DESIGN: The study design consisted of a randomly selected,
      cross-sectional, population-based study of 2633 individuals surveyed in 1991, of
      whom 1597 participants provided paired urinary and blood samples permitting
      measurement of 24-h urinary sodium excretion and serum C-reactive protein (CRP)
      concentrations. RESULTS: The mean (+/-SD) 24-h sodium intake for the population
      was 177 +/- 69 mmol. In the basic model adjusted for age, sex, and smoking,
      higher levels of 24-h sodium excretion were directly associated with serum CRP,
      with an increase in serum CRP of 1.20 mg/L per 100-mmol increment in sodium
      excretion (95% CI: 1.11, 1.30). However, this association was reduced after
      adjustment for body mass index, with an increase in serum CRP of 1.06 mg/L per
      100-mmol increment in sodium excretion (95% CI: -1.02, 1.15). CONCLUSIONS: We
      observed a linear association between an objective measure of sodium intake and
      serum CRP that may be influenced by confounding by body mass index. The magnitude
      of these associations suggests that dietary sodium consumption is unlikely to be
      an important modifiable risk factor for increased systemic inflammation.

PMID- 19386746
TI  - Comparison of self-reported, measured, metabolizable energy intake with total
      energy expenditure in overweight teens.
AB  - BACKGROUND: The accuracy of dietary energy assessment tools is critical to
      understanding the role of diet in the increasing rate of obesity. OBJECTIVES: The
      purposes of our study in overweight adolescent boys and girls were 1) to assess
      the energy reporting bias of diet records against the referent of total energy
      expenditure (TEE) and 2) to compare the methods of determining energy needs by
      using measured metabolizable energy intake (MEI) and TEE. DESIGN: Twenty girls
      [12-15 y, body mass index (in kg/m2) = 33.0 +/- 5] and 14 boys (12-14 y, body
      mass index = 27.4 +/- 4) participated in 2- to 3-wk metabolic balance studies.
      TEE was measured by using doubly labeled water (TEE(DLW)), and MEI was measured
      by bomb calorimetry of composite daily diet, urine, and fecal collections. Food
      records were collected before each study. RESULTS: Food records underreported
      TEE(DLW) by 35 +/- 20%. Underreporting of energy intake was correlated with all
      macronutrient intake concentrations (g or kcal) (P < 0.0001). A multiple
      regression model showed that 86.4% of the variance in underreporting error was
      explained by dietary fat (g), BMI, and sex. The intrasubject CV was 3.9% for
      TEE(DLW) and 9.9% for MEI. MEI for weight stability (MEI(wtstb)) averaged 99 +/-
      11% of TEE. CONCLUSIONS: The increased underreporting of dietary intake with
      increasing body weight in teens may explain in part previous reports noting that
      there has been an increased incidence of obesity, although energy intakes have
      not appeared to increase. MEI(wtstb) and TEE(DLW) gave similar estimates of
      energy needs. This trial was registered at clinicaltrials.gov as NCT 00592137.

PMID- 19386747
TI  - Lower protein in infant formula is associated with lower weight up to age 2 y: a
      randomized clinical trial.
AB  - BACKGROUND: Protein intake during infancy was associated with rapid early weight
      gain and later obesity in observational studies. OBJECTIVE: The objective was to
      test the hypothesis that higher protein intake in infancy leads to more rapid
      length and weight gain in the first 2 y of life. DESIGN: In a multicenter
      European study, 1138 healthy, formula-fed infants were randomly assigned to
      receive cow milk-based infant and follow-on formula with lower (1.77 and 2.2 g
      protein/100 kcal, respectively) or higher (2.9 and 4.4 g protein/100 kcal,
      respectively) protein contents for the first year. For comparison, 619
      exclusively breastfed children were also followed. Weight, length, weight-for
      length, and BMI were determined at inclusion and at 3, 6, 12, and 24 mo of age.
      The primary endpoints were length and weight at 24 mo of age, expressed as length
      and weight-for-length z scores based on the 2006 World Health Organization growth
      standards. RESULTS: Six hundred thirty-six children in the lower (n = 313) and
      higher (n = 323) protein formula groups and 298 children in the breastfed group
      were followed until 24 mo. Length was not different between randomized groups at
      any time. At 24 mo, the weight-for-length z score of infants in the lower protein
      formula group was 0.20 (0.06, 0.34) lower than that of the higher protein group
      and did not differ from that of the breastfed reference group. CONCLUSIONS: A
      higher protein content of infant formula is associated with higher weight in the
      first 2 y of life but has no effect on length. Lower protein intake in infancy
      might diminish the later risk of overweight and obesity. This trial was
      registered at clinicaltrials.gov as NCT00338689.

PMID- 19386748
TI  - Effect of treatment frequency on haemodialysis dose: comparison of EKR and
      stdKt/V.
AB  - BACKGROUND: Haemodialysis outcome cannot be improved by increasing the dialysis
      session dose above the current standard in conventional schedules. Promising
      results have been reported from daily dialysis, but the optimal dose has not been
      established. METHODS: Weekly eKt/V, equivalent renal clearance (EKR) and stdKt/V
      were compared retrospectively in 588 complete urea kinetic modelling sessions of
      35 haemodialysis patients. Equivalent values of EKR and stdKt/V corresponding to
      the standard and high doses of the HEMO study were defined by computer
      simulation. The effect of frequency on the dose measures was demonstrated by
      simulating different schedules. RESULTS: EKR and stdKt/V take into consideration
      both frequency and RRF, but appreciate them differently. The values of EKRc (EKR
      in millilitres per minute, normalized to distribution volume 40 l), stdEKR (EKR
      in litres per week divided by urea distribution volume in litres) and stdKt/V
      corresponding to eKt/V 1.20-close to the standard dose in the HEMO study-were
      13.2 ml/min/40 l, 3.34/wk and 2.23/wk, respectively. stdKt/V appreciates
      frequency more than EKR. A spreadsheet was created to compute the dialysis
      session time to achieve the EKR or stdKt/V target when the basic urea kinetic
      variables are known. CONCLUSIONS: Haemodialysis efficiency can be increased by
      increasing frequency. EKR and stdKt/V are more appropriate than weekly eKt/V as
      measures of dialysis dose in different schedules. With increasing frequency,
      stdKt/V as the dosing target results in shorter treatment times and higher
      concentrations than EKR.

PMID- 19386749
TI  - Ischaemia/reperfusion in rat renal cortex: vesicle leakiness and Na+, K+-ATPase
      activity in membrane preparations.
AB  - BACKGROUND: Despite the central role of Na(+), K(+)-ATPase (NKA) in ischaemic
      renal injury (IRI), cortical NKA activity values during renal ischaemia remain
      controversial. In this study, we explore why cortical NKA activity shows such
      behaviour during ischaemia in rats. METHODS: Ischaemia was induced by unilateral
      renal artery clamping (40 min, I) followed or not by reperfusion (60 min, IR).
      NKA alpha- and beta-subunit abundance was analysed by western blot. We studied
      the NKA detergent sodium dodecyl sulphate (SDS) enzymatic activation in isolated
      membrane preparations from control and ischaemic kidneys. RESULTS: NKA activity
      was diminished in I cortical homogenates (C = 9.3 +/- 1.1, I = 4.7 +/- 1.1*
      micromol Pi/h mg Prot, n = 4-6, *P < 0.05 versus C). This was rapidly recovered
      after reperfusion (IR = 9.9 +/- 1.2 micromol Pi/h mg Prot). alpha-subunit levels
      were increased, while beta-subunit was unchanged. At SDS 0.9 mg/ml (maximal
      detergent activation), the activities were indistinguishable (C = 90.5 +/- 2.2, I
      = 91.4 +/- 15.1 micromol Pi/h mg Prot). The analysis of detergent activation of
      NKA activity is widely used to estimate membrane leakiness in plasma membrane
      preparations. Our results suggest a higher population of sealed impermeable
      vesicles in preparations from ischaemic renal tissue. CONCLUSION: The well-known
      effect of ischaemia on renal cell cytoskeleton could explain the observed changes
      in the leakiness of membrane vesicles.

PMID- 19386750
TI  - Multisensory integration in mesencephalic trigeminal neurons in Xenopus tadpoles.
AB  - Mesencephalic trigeminal (M-V) neurons are primary somatosensory neurons with
      somata located within the CNS, instead of in peripheral sensory ganglia. In
      amphibians, these unipolar cells are found within the optic tectum and have a
      single axon that runs along the mandibular branch of the trigeminal nerve. The
      axon has collaterals in the brain stem and is believed to make synaptic contact
      with neurons in the trigeminal motor nucleus, forming part of a sensorimotor
      loop. The number of M-V neurons is known to increase until metamorphosis and then
      decrease, suggesting that at least some M-V neurons may play a transient role
      during tadpole development. It is not known whether their location in the optic
      tectum allows them to process both visual and somatosensory information. Here we
      compare the anatomical and electrophysiological properties of M-V neurons in the
      Xenopus tadpole to principal tectal neurons. We find that, unlike principal
      tectal cells, M-V neurons can sustain repetitive spiking when depolarized and
      express a significant H-type current. M-V neurons could also be driven
      synaptically by visual input both in vitro and in vivo, but visual responses were
      smaller and longer-lasting than those seen in principal tectal neurons. We also
      found that the axon of M-V neurons appears to directly innervate a tentacle found
      in the corner of the mouth of premetamorphic tadpoles. Electrical stimulation of
      this transient sensory organ results in antidromic spiking in M-V neurons in the
      tectum. Thus M-V neurons may play an integrative multisensory role during tadpole
      development.

PMID- 19386751
TI  - Loss of potassium homeostasis underlies hyperthermic conduction failure in
      control and preconditioned locusts.
AB  - At extreme temperature, neurons cease to function appropriately. Prior exposure
      to a heat stress (heat shock [HS]) can extend the temperature range for action
      potential conduction in the axon, but how this occurs is not well understood.
      Here we use electrophysiological recordings from the axon of a locust visual
      interneuron, the descending contralateral movement detector (DCMD), to examine
      what physiological changes result in conduction failure and what modifications
      allow for the observed plasticity following HS. We show that at high temperature,
      conduction failure in the DCMD occurred preferentially where the axon passes
      through the thoracic ganglia rather than in the connective. Although the membrane
      potential hyperpolarized with increasing temperature, we observed a modest
      depolarization (3-6 mV) in the period preceding the failure. Prior to the
      conduction block, action potential amplitude decreased and half-width increased.
      Both of these failure-associated effects were attenuated following HS.
      Extracellular potassium concentration ([K+]o) increased sharply at failure and
      the failure event could be mimicked by the application of high [K+]o. Surges in
      [K+]o were muted following HS, suggesting that HS may act to stabilize ion
      distribution. Indeed, experimentally increased [K+]o lowered failure temperature
      significantly more in control animals than in HS animals and experimentally
      maintained [K+]o was found to be protective. We suggest that the more attenuated
      effects of failure on the membrane properties of the DCMD axon in HS animals is
      consistent with a decrease in the disruptive nature of the [K+]o-dependent
      failure event following HS and thus represents an adaptive mechanism to cope with
      thermal stress.

PMID- 19386752
TI  - Synergistic roles of GABAA receptors and SK channels in regulating
      thalamocortical oscillations.
AB  - Rhythmic oscillations throughout the cortex are observed during physiological and
      pathological states of the brain. The thalamus generates sleep spindle
      oscillations and spike-wave discharges characteristic of absence epilepsy. Much
      has been learned regarding the mechanisms underlying these oscillations from in
      vitro brain slice preparations. One widely used model to understand the
      epileptiform oscillations underlying absence epilepsy involves application of
      bicuculline methiodide (BMI) to brain slices containing the thalamus. BMI is a
      well-known GABAA receptor blocker that has previously been discovered to also
      block small-conductance, calcium-activated potassium (SK) channels. Here we
      report that the robust epileptiform oscillations observed during BMI application
      rely synergistically on both GABAA receptor and SK channel antagonism. Neither
      application of picrotoxin, a selective GABAA receptor antagonist, nor application
      of apamin, a selective SK channel antagonist, alone yielded the highly
      synchronized, long-lasting oscillations comparable to those observed during BMI
      application. However, partial blockade of SK channels by subnanomolar
      concentrations of apamin combined with picrotoxin sufficiently replicated BMI
      oscillations. We found that, at the cellular level, apamin enhanced the intrinsic
      excitability of reticular nucleus (RT) neurons but had no effect on relay
      neurons. This work suggests that regulation of RT excitability by SK channels can
      influence the excitability of thalamocortical networks and may illuminate
      possible pharmacological treatments for absence epilepsy. Finally, our results
      suggest that changes in the intrinsic properties of individual neurons and
      changes at the circuit level can robustly modulate these oscillations.

PMID- 19386754
TI  - Developmental changes in dendritic shape and synapse location tune single-neuron
      computations to changing behavioral functions.
AB  - During nervous system development, different classes of neurons obtain different
      dendritic architectures, each of which receives a large number of input synapses.
      However, it is not clear whether synaptic inputs are targeted to specific regions
      within a dendritic tree and whether dendritic tree geometry and subdendritic
      synapse distributions might be optimized to support proper neuronal input-output
      computations. This study uses an insect model where structure and function of an
      individually identifiable neuron, motoneuron 5 (MN5), are changed while it
      develops from a slow larval crawling into a fast adult flight motoneuron during
      metamorphosis. This allows for relating postembryonic dendritic remodeling of an
      individual motoneuron to developmental changes in behavioral function. Dendritic
      architecture of MN5 is analyzed by three-dimensional geometric reconstructions
      and quantitative co-localization analysis to address the distribution of synaptic
      terminals. Postembryonic development of MN5 comprises distinct changes in
      dendritic shape and in the subdendritic distribution of GABAergic input synapses
      onto MN5. Subdendritic synapse targeting is not a consequence of neuropil
      structure but must rely on specific subdendritic recognition mechanisms. Passive
      multicompartment simulations indicate that postembryonic changes in dendritic
      architecture and in subdendritic input synapse distributions may tune the passive
      computational properties of MN5 toward stage-specific behavioral requirements.

PMID- 19386753
TI  - Task-dependent modulation of primary afferent depolarization in cervical spinal
      cord of monkeys performing an instructed delay task.
AB  - Task-dependent modulation of primary afferent depolarization (PAD) was studied in
      the cervical spinal cord of two monkeys performing a wrist flexion and extension
      task with an instructed delay period. We implanted two nerve cuff electrodes on
      proximal and distal parts of the superficial radial nerve (SR) and a recording
      chamber over a hemi-laminectomy in the lower cervical vertebrae. Antidromic
      volleys (ADVs) in the SR were evoked by intraspinal microstimuli (ISMS, 3-10 Hz,
      3-30 microA) applied through a tungsten microelectrode, and the area of each ADV
      was measured. In total, 434 ADVs were evoked by ISMS in two monkeys, with onset
      latency consistently shorter in the proximal than distal cuffs. Estimated
      conduction velocity suggest that most ADVs were caused by action potentials in
      cutaneous fibers originating from low-threshold tactile receptors. Modulation of
      the size of ADVs as a function of the task was examined in 281 ADVs induced by
      ISMS applied at 78 different intraspinal sites. The ADVs were significantly
      facilitated during active movement in both flexion and extension (P<0.05),
      suggesting an epoch-dependent modulation of PAD. This facilitation started 400
      900 ms before the onset of EMG activity. Such pre-EMG modulation is hard to
      explain by movement-induced reafference and probably is associated with
      descending motor commands.

PMID- 19386755
TI  - Cholecystokinin excites interneurons in rat basolateral amygdala.
AB  - The amygdala formation is implicated in generation of emotional states such as
      anxiety and fear. Many substances that modulate neuronal activity in the amygdala
      alter anxiety. Cholecystokinin (CCK) is an endogenous neuropeptide that induces
      anxiety states in behavioral studies in both animals and humans. Using a brain
      slice preparation, we found that application of CCK increases inhibitory synaptic
      transmission measured in projection neurons of the basolateral amygdala. To
      determine the source of the increased inhibition we examined the direct effect of
      CCK on local interneurons in this region. CCK most strongly depolarized fast
      spiking interneurons. Burst-firing and regular-firing interneurons were also
      depolarized, although to a lesser degree. However, another distinct group of
      interneurons was unaffected by CCK. These effects were mediated by the CCKB
      receptor subtype. The excitatory effect of CCK appeared to be mediated by both a
      nonselective cation and a K+ current.

PMID- 19386756
TI  - Whole cell recordings from visualized neurons in the inner laminae of the
      functionally intact spinal cord.
AB  - The in vitro whole spinal cord preparation has been an invaluable tool for the
      study of the neural network that underlies walking because it provides a means of
      recording fictive locomotor activity following surgical and/or pharmacological
      manipulation. The recent use of molecular genetic techniques to identify discrete
      neuronal populations in the spinal cord and subsequent studies showing some of
      these populations to be involved in locomotor activity have been exciting
      developments that may lead to a better understanding of the structure and
      mechanism of function of this neural network. It would be of great benefit if the
      in vitro whole spinal cord preparation could be updated to allow for the direct
      targeting of genetically defined neuronal populations, allowing each to be
      characterized physiologically and anatomically. This report describes a new
      technique that enables the visualization of, and targeted whole cell patch-clamp
      recordings from, genetically defined populations of neurons while leaving
      connectivity largely intact. The key feature of this technique is a small notch
      cut in the lumbar spinal cord that reveals cells located in the intermediate
      laminae while leaving the ventral portion of the spinal cord-the region
      containing the locomotor neural network-untouched. Whole cell patch-clamp
      recordings demonstrate that these neurons are healthy and display large rhythmic
      depolarizations that are related to electroneurogram bursts recorded from ventral
      roots during fictive locomotion. Intracellular labeling demonstrates that this
      technique can also be used to map axonal projection patterns of neurons. We
      expect that this procedure will greatly facilitate electrophysiological and
      anatomical study of important neuronal populations that constitute neural
      networks throughout the CNS.

PMID- 19386757
TI  - Brain polarization enhances the formation and retention of motor memories.
AB  - One of the first steps in the acquisition of a new motor skill is the formation
      of motor memories. Here we tested the capacity of transcranial DC stimulation
      (tDCS) applied over the motor cortex during motor practice to increase motor
      memory formation and retention. Nine healthy individuals underwent a crossover
      transcranial magnetic stimulation (TMS) study designed to test motor memory
      formation resulting from training. Anodal tDCS elicited an increase in the
      magnitude and duration of motor memories in a polarity-specific manner, as
      reflected by changes in the kinematic characteristics of TMS-evoked movements
      after anodal, but not cathodal or sham stimulation. This effect was present only
      when training and stimulation were associated and mediated by a differential
      modulation of corticomotor excitability of the involved muscles. These results
      indicate that anodal brain polarization can enhance the initial formation and
      retention of a new motor memory resulting from training. These processes may be
      the underlying mechanisms by which tDCS enhances motor learning.

PMID- 19386758
TI  - Regulation of cation channel voltage and Ca2+ dependence by multiple modulators.
AB  - Ion channel regulation is key to controlling neuronal excitability. However, the
      extent that modulators and gating factors interact to regulate channels is less
      clear. For Aplysia, a nonselective cation channel plays an essential role in
      reproduction by driving an afterdischarge in the bag cell neurons to elicit egg
      laying hormone secretion. We examined the regulation of cation channel voltage
      and Ca2+ dependence by protein kinase C (PKC) and inositol trisphosphate (IP3)
      two prominent afterdischarge signals. In excised, inside-out patches, the channel
      remained open longer and reopened more often with depolarization from -90 to +30
      mV. As previously reported, PKC could closely associate with the channel and
      increase activity at -60 mV. We now show that, following the effects of PKC,
      voltage dependence was shifted to the left (essentially enhanced), particularly
      at more negative voltages. Conversely, the voltage dependence of channels lacking
      PKC was shifted to the right (essentially suppressed). Predictably, activity was
      increased at all Ca2+ concentrations following the effects of PKC; nevertheless,
      Ca2+ dependence was actually shifted to the right. Moreover, whereas IP3 did not
      alter activity at -60 mV, it drastically shifted Ca2+ dependence to the right-an
      outcome largely reversed by PKC. With respect to the afterdischarge, these data
      suggest PKC initially upregulates the channel by direct gating and shifting
      voltage dependence to the left. Subsequently, PKC and IP3 attenuate the channel
      by suppressing Ca2+ dependence. This ensures hormone delivery by allowing
      afterdischarge initiation and maintenance but also prevents interminable
      bursting. Similar regulatory interactions may be used by other neurons to achieve
      diverse outputs.

PMID- 19386759
TI  - Wireless neural stimulation in freely behaving small animals.
AB  - We introduce a novel wireless, low-power neural stimulation system for use in
      freely behaving animals. The system consists of an external transmitter and a
      miniature, implantable wireless receiver-stimulator. The implant uses a custom
      integrated chip to deliver biphasic current pulses to four addressable bipolar
      electrodes at 32 selectable current levels (10 microA to 1 mA). To achieve
      maximal battery life, the chip enters a sleep mode when not needed and can be
      awakened remotely when required. To test our device, we implanted bipolar
      stimulating electrodes into the songbird motor nucleus HVC (formerly called the
      high vocal center) of zebra finches. Single-neuron recordings revealed that
      wireless stimulation of HVC led to a strong increase of spiking activity in its
      downstream target, the robust nucleus of the arcopallium. When we used this
      device to deliver biphasic pulses of current randomly during singing, singing
      activity was prematurely terminated in all birds tested. Thus our device is
      highly effective for remotely modulating a neural circuit and its corresponding
      behavior in an untethered, freely behaving animal.

PMID- 19386760
TI  - Reverse optical trawling for synaptic connections in situ.
AB  - We introduce a new method to unveil the network connectivity among dozens of
      neurons in brain slice preparations. While synaptic inputs were whole cell
      recorded from given postsynaptic neurons, the spatiotemporal firing patterns of
      presynaptic neuron candidates were monitored en masse with functional multineuron
      calcium imaging, an optical technique that records action potential-evoked
      somatic calcium transients with single-cell resolution. By statistically
      screening the neurons that exhibited calcium transients immediately before the
      postsynaptic inputs, we identified the presynaptic cells that made synaptic
      connections onto the patch-clamped neurons. To enhance the detection power, we
      devised the following points: 1) [K+]e was lowered and [Ca2+]e and [Mg2+]e were
      elevated, to reduce background synaptic activity and minimize the failure rate of
      synaptic transmission; and 2) a small fraction of presynaptic neurons was
      specifically activated by glutamate applied iontophoretically through a glass
      pipette that was moved to survey the presynaptic network of interest
      ("trawling"). Then we could theoretically detect 96% of presynaptic neurons
      activated in the imaged regions with a 1% false-positive error rate. This on-line
      probing technique would be a promising tool in the study of the wiring topography
      of neuronal circuits.

PMID- 19386761
TI  - Humanin inhibits neuronal cell death by interacting with a cytokine receptor
      complex or complexes involving CNTF receptor alpha/WSX-1/gp130.
AB  - Humanin (HN) inhibits neuronal death induced by various Alzheimer's disease (AD)
      related insults via an unknown receptor on cell membranes. Our earlier study
      indicated that the activation of STAT3 was essential for HN-induced
      neuroprotection, suggesting that the HN receptor may belong to the cytokine
      receptor family. In this study, a series of loss-of-function tests indicated that
      gp130, the common subunit of receptors belonging to the IL-6 receptor family, was
      essential for HN-induced neuroprotection. Overexpression of ciliary neurotrophic
      factor receptor alpha (CNTFR) and/or the IL-27 receptor subunit, WSX-1, but not
      that of any other tested gp130-related receptor subunit, up-regulated HN binding
      to neuronal cells, whereas siRNA-mediated knockdown of endogenous CNTFR and/or
      WSX-1 reduced it. These results suggest that both CNTFR and WSX-1 may be also
      involved in HN binding to cells. Consistent with these results, loss-of-functions
      of CNTFR or WSX-1 in neuronal cells nullified their responsiveness to HN-mediated
      protection. In vitro-reconstituted binding assays showed that HN, but not the
      other control peptide, induced the hetero-oligomerization of CNTFR, WSX-1, and
      gp130. Together, these results indicate that HN protects neurons by binding to a
      complex or complexes involving CNTFR/WSX-1/gp130.

PMID- 19386762
TI  - The mating-specific Galpha interacts with a kinesin-14 and regulates pheromone
      induced nuclear migration in budding yeast.
AB  - As a budding yeast cell elongates toward its mating partner, cytoplasmic
      microtubules connect the nucleus to the cell cortex at the growth tip. The Kar3
      kinesin-like motor protein is then thought to stimulate plus-end depolymerization
      of these microtubules, thus drawing the nucleus closer to the site where cell
      fusion and karyogamy will occur. Here, we show that pheromone stimulates a
      microtubule-independent interaction between Kar3 and the mating-specific Galpha
      protein Gpa1 and that Gpa1 affects both microtubule orientation and cortical
      contact. The membrane localization of Gpa1 was found to polarize early in the
      mating response, at about the same time that the microtubules begin to attach to
      the incipient growth site. In the absence of Gpa1, microtubules lose contact with
      the cortex upon shrinking and Kar3 is improperly localized, suggesting that Gpa1
      is a cortical anchor for Kar3. We infer that Gpa1 serves as a positional
      determinant for Kar3-bound microtubule plus ends during mating.

PMID- 19386763
TI  - Timely septation requires SNAD-dependent spindle pole body localization of the
      septation initiation network components in the filamentous fungus Aspergillus
      nidulans.
AB  - In the filamentous fungus Aspergillus nidulans, cytokinesis/septation is
      triggered by the septation initiation network (SIN), which first appears at the
      spindle pole body (SPB) during mitosis. The coiled-coil protein SNAD is
      associated with the SPB and is required for timely septation and conidiation. We
      have determined that SNAD acted as a scaffold protein that is required for the
      localization of the SIN proteins of SIDB and MOBA to the SPB. Another scaffold
      protein SEPK, whose localization at the SPB was dependent on SNAD, was also
      required for SIDB and MOBA localization to the SPB. In the absence of either SEPK
      or SNAD, SIDB/MOBA successfully localized to the septation site, indicating that
      their earlier localization at SPB was not essential for their later appearance at
      the division site. Unlike their functional counterparts in fission yeast, SEPK
      and SNAD were not required for vegetative growth but only for timely septation.
      Furthermore, down-regulation of negative regulators of the SIN suppressed the
      septation and conidiation phenotypes due to the loss of SNAD. Therefore, we
      conclude that SPB localization of SIN components is not essential for septation
      per se, but critical for septation to take place in a timely manner in A.
      nidulans.

PMID- 19386764
TI  - Specificity of cytoplasmic dynein subunits in discrete membrane-trafficking
      steps.
AB  - The cytoplasmic dynein motor complex is known to exist in multiple forms, but few
      specific functions have been assigned to individual subunits. A key limitation in
      the analysis of dynein in intact mammalian cells has been the reliance on gross
      perturbation of dynein function, e.g., inhibitory antibodies, depolymerization of
      the entire microtubule network, or the use of expression of dominant negative
      proteins that inhibit dynein indirectly. Here, we have used RNAi and automated
      image analysis to define roles for dynein subunits in distinct membrane
      trafficking processes. Depletion of a specific subset of dynein subunits, notably
      LIC1 (DYNC1LI1) but not LIC2 (DYNC1LI2), recapitulates a direct block of ER
      export, revealing that dynein is required to maintain the steady-state
      composition of the Golgi, through ongoing ER-to-Golgi transport. Suppression of
      LIC2 but not of LIC1 results in a defect in recycling endosome distribution and
      cytokinesis. Biochemical analyses also define the role of each subunit in
      stabilization of the dynein complex; notably, suppression of DHC1 or IC2 results
      in concomitant loss of Tctex1. Our data demonstrate that LIC1 and LIC2 define
      distinct dynein complexes that function at the Golgi versus recycling endosomes,
      respectively, suggesting that functional populations of dynein mediate discrete
      intracellular trafficking pathways.

PMID- 19386765
TI  - Rab7 activation by growth factor withdrawal contributes to the induction of
      apoptosis.
AB  - The Rab7 GTPase promotes membrane fusion reactions between late endosomes and
      lysosomes. In previous studies, we demonstrated that Rab7 inactivation blocks
      growth factor withdrawal-induced cell death. These results led us to hypothesize
      that growth factor withdrawal activates Rab7. Here, we show that growth factor
      deprivation increased both the fraction of Rab7 that was associated with cellular
      membranes and the percentage of Rab7 bound to guanosine triphosphate (GTP).
      Moreover, expressing a constitutively GTP-bound mutant of Rab7, Rab7-Q67L, was
      sufficient to trigger cell death even in the presence of growth factors. This
      activated Rab7 mutant was also able to reverse the growth factor-independent cell
      survival conferred by protein kinase C (PKC) delta inhibition. PKCdelta is one of
      the most highly induced proteins after growth factor withdrawal and contributes
      to the induction of apoptosis. To evaluate whether PKCdelta regulates Rab7, we
      first examined lysosomal morphology in cells with reduced PKCdelta activity.
      Consistent with a potential role as a Rab7 activator, blocking PKCdelta function
      caused profound lysosomal fragmentation comparable to that observed when Rab7 was
      directly inhibited. Interestingly, PKCdelta inhibition fragmented the lysosome
      without decreasing Rab7-GTP levels. Taken together, these results suggest that
      Rab7 activation by growth factor withdrawal contributes to the induction of
      apoptosis and that Rab7-dependent fusion reactions may be targeted by signaling
      pathways that limit growth factor-independent cell survival.

PMID- 19386766
TI  - Vimentin regulates scribble activity by protecting it from proteasomal
      degradation.
AB  - Scribble (Scrib), Discs large, and Lethal giant larvae form a protein complex
      that regulates different aspects of cell polarization, including apical-basal
      asymmetry in epithelial cells and anterior-posterior polarity in migrating cells.
      Here, we show that Scrib interacts with the intermediate filament cytoskeleton in
      epithelial Madin-Darby canine kidney (MDCK) cells and endothelial human umbilical
      vein endothelial cells. Scrib binds vimentin via its postsynaptic density 95/disc
      large/zona occludens domains and in MDCK cells redistributes from filaments to
      the plasma membrane during the establishment of cell-cell contacts. RNA
      interference-mediated silencing of Scrib, vimentin, or both in MDCK cells results
      in defects in the polarization of the Golgi apparatus during cell migration.
      Concomitantly, wound healing is delayed due to the loss of directional movement.
      Furthermore, cell aggregation is dependent on both Scrib and vimentin. The
      similar phenotypes observed after silencing either Scrib or vimentin support a
      coordinated role for the two proteins in cell migration and aggregation.
      Interestingly, silencing of vimentin leads to an increased proteasomal
      degradation of Scrib. Thus, the upregulation of vimentin expression during
      epithelial to mesenchymal transitions may stabilize Scrib to promote directed
      cell migration.

PMID- 19386767
TI  - Moments of weakness: the implicit context dependencies of temptations.
AB  - The implicit appeal of temptations may vary by the social and self-regulatory
      contexts in which they are encountered. In each of four studies, participants
      were subliminally primed with the name of someone associated with either drug use
      or drug abstinence, after which their own motives toward drug use were assessed.
      Results indicate that the appeal of this temptation often depended on
      participants' chronicity of indulgence (Study 1), relationship closeness with the
      tempter (Study 2), self-regulatory effectiveness (Study 3), and goal
      disengagement tendencies (Study 4). Although the influence of tempters may be
      automatic, it is also a dynamic process and these findings suggest that the
      appeal of temptations varies both situationally and motivationally.

PMID- 19386768
TI  - Dimerization of Kit-ligand and efficient cell-surface presentation requires a
      conserved Ser-Gly-Gly-Tyr motif in its transmembrane domain.
AB  - Kit-ligand (Kitl), also known as stem cell factor, is a membrane-anchored,
      noncovalently bound dimer signaling via the c-kit receptor tyrosine kinase,
      required for migration, survival, and proliferation of hematopoietic stem and
      germ cells, melanocytes, and mastocytes. Despite its fundamental role in
      morphogenesis and stem cell biology, the mechanisms that regulate Kitl
      dimerization are not well understood. By employing cell-permeable cross-linker
      and quantitative bimolecular fluorescence complementation of wild-type and
      truncated forms of Kitl, we determined that Kitl dimerization is initiated in the
      endoplasmic reticulum and mediated to similar levels by the transmembrane and the
      extracellular growth factor domain. Further biochemical and mutational analysis
      revealed a conserved Ser-Gly-Gly-Tyr-containing motif that is required for
      transmembrane domain dimerization and efficient cell-surface expression of Kitl.
      A novel intracellular capture assay with the Kitl transmembrane domain as bait
      revealed specific interactions with Kitl, but not with unrelated transmembrane
      proteins. During evolution, the transmembrane dimerization motif appeared in Kitl
      at the transition from teleosts to tetrapods, which correlates with the emergence
      of Kitl as a supporter of stem cell populations. Thus, transmembrane-mediated
      association of membrane-anchored growth factors consists of a novel mechanism to
      improve paracrine signaling and morphogenesis.

PMID- 19386769
TI  - Brief report: unintentional injury risk among children with sensory impairments.
AB  - OBJECTIVE: Pediatric injuries result from a multifaceted process involving a
      range of individual, interpersonal, and environmental influences. One risk that
      remains poorly understood is the role of children's perception and perceptual
      disabilities. METHODS: Injury counts (parent-report of injuries requiring
      professional medical treatment over the past year) in three groups of children
      were compared: those without vision or hearing sensory impairments, those with
      deficits who use eyeglasses or hearing aids, and those with deficits who do not
      use aids as recommended. A national sample of 7391 5-year-olds in the National
      Head Start/Public School Early Childhood Transition Demonstration Study was
      studied. RESULTS: Injury counts over the past year were higher among children
      with sensory impairments, and higher still among children with sensory
      impairments who did not use prescribed sensory aids. CONCLUSIONS: Awareness of
      increased injury risk among children with hearing and vision impairment could
      help professionals protect children from injury.

PMID- 19386770
TI  - Enhancing pain management in the PICU by teaching guided mental imagery: a
      quality-improvement project.
AB  - OBJECTIVE: This quality-improvement study, following the PDCA methodology,
      compared the effectiveness of teaching mental imagery (MI) for pain management
      versus conducting a detailed inquiry (DI) about pain-related experiences with
      acutely injured PICU patients. METHODS: Participants included 44 hospitalized
      children and adolescents assigned to one of two intervention groups, MI (N = 24)
      or DI (N = 20). Pain was assessed pre- and post-intervention using the Wong-Baker
      Faces Pain Rating Scale and a 0-10 Likert pain rating scale, and the Pediatric
      Trauma Score was utilized to assess the severity of each child's injuries.
      RESULTS: Boys in the MI condition exhibited a significant decrease in average
      pain ratings [t(38) = 3.41, p = .0015]. Girls in the MI condition exhibited a non
      significant decrease in average pain ratings. CONCLUSIONS: Teaching children the
      use of MI for pain management in an intensive-care setting was supported; the use
      of DI with boys was not supported.

PMID- 19386772
TI  - On the need for a radiation accident registry in Canada.
AB  - To be able to respond effectively to any radiological or nuclear emergency, a
      radiation accident registry is a valuable asset. This type of registry is able to
      assist responders in preparing for and managing situations during the event and
      in providing effective follow-up on the long-term health effects of persons
      exposed. It is especially important to register radiation-exposed people in
      vulnerable population groups, such as children and pregnant women, to ensure
      proper long-term health care and protection. As part of its national system of
      emergency preparedness for response to radiological or nuclear events, Canada
      needs to develop a plan for a radiation accident registry. Apart from radiation
      dose information, this registry should also contain a sub-database of available
      medical facilities and necessary supplies as well as professionals specialising
      in radiation treatment and protection. Following the establishment of the
      registry, it should routinely be tested in training exercises to ensure its
      readiness for implementation whenever the need might arise.

PMID- 19386773
TI  - Simultaneous 222Rn and 220Rn measurements in Winnipeg, Canada.
AB  - Naturally occurring isotopes of radon in indoor air are identified as the second
      leading cause of lung cancer after tobacco smoking. Winnipeg had the highest
      radon ((222)Rn) concentration among 18 Canadian cities surveyed in the past.
      There is great interest to know the current radon as well as thoron ((220)Rn)
      concentrations in Winnipeg homes. Therefore, radon-thoron discrimination
      detectors were deployed in 117 houses for a period of 3 months. The results
      confirmed that thoron is present at detectable levels in about half of the
      Winnipeg homes and radon remains significantly higher than the national average.
      In this study, radon concentrations ranged from 20 to 483 Bq m(-3) with a
      geometric mean of 112 Bq m(-3) and a geometric standard deviation of 2.07. It is
      estimated that 20% of Winnipeg homes could have radon concentrations above the
      Canadian indoor radon guideline of 200 Bq m(-3). This conclusion is similar to
      the previous estimation made 20 y ago. Thoron concentrations were below the
      detection limit in 60 homes. Among the homes with detectable thoron
      concentrations, the values varied from 5 to 297 Bq m(-3), the geometric mean and
      standard deviation were 21 Bq m(-3) and 2.53, respectively.

PMID- 19386771
TI  - A mediation analysis of the ATHENA intervention for female athletes: prevention
      of athletic-enhancing substance use and unhealthy weight loss behaviors.
AB  - OBJECTIVE: To explain, through mediation analyses, the mechanisms by which ATHENA
      (Athletes Targeting Healthy Exercise and Nutrition Alternatives), a primary
      prevention and health promotion intervention designed to deter unhealthy body
      shaping behaviors among female high school athletes, produced immediate changes
      in intentions for unhealthy weight loss and steroid/creatine use, and to examine
      the link to long-term follow-up intentions and behaviors. METHODS: In a
      randomized trial of 1668 athletes, intervention participants completed coach-led
      peer-facilitated sessions during their sport season. Participants provided pre
      test, immediate post-test, and 9-month follow-up assessments. RESULTS: ATHENA
      decreased intentions for steroid/creatine use and intentions for unhealthy weight
      loss behaviors at post-test. These effects were most strongly mediated by social
      norms and self-efficacy for healthy eating. Low post-test intentions were
      maintained 9 months later and predicted subsequent behavior. CONCLUSIONS: ATHENA
      successfully modified mediators that in turn related to athletic-enhancing
      substance use and unhealthy weight loss practices. Mediation analyses aid in the
      understanding of health promotion interventions and inform program development.

PMID- 19386774
TI  - Radioactivity concentrations in soil and vegetables from the northern Jordan Rift
      Valley and the corresponding dose estimates.
AB  - The Jordan Rift Valley (JRV) is considered the food bowl of Jordan, especially
      during the winter season. In this study, soil and vegetable samples collected
      from greenhouses in the northern JRV were analysed for their radioactive content.
      The activity concentrations of (238)U, (235)U, (232)Th, (226)Ra, (137)Cs and
      (40)K in soil were found to be (+/-SD) 33 +/- 12, 2.2 +/- 0.7, 11.2 +/- 3.3, 40.5
      +/- 15.5, 3.5 +/- 1.3 and 156.0 +/- 46.6 (Bq kg(-1)), respectively. In
      vegetables, the activity concentration of (40)K was found in the range of 698
      1439 Bq kg(-1), while those of (226)Ra and (228)Ra were found to be in the range
      of <0.61-2.56 and <0.69-3.35 Bq kg(-1), respectively. Transfer factors for (40)K
      were found to be high and ranged from 5 to 8, while those for (226)Ra and (228)Ra
      were found to be from <0.01 to 0.07 and from <0.09 to 0.42, respectively. The
      calculated external annual effective dose is found to be within the worldwide
      range.

PMID- 19386775
TI  - On the effect of updated MCNP photon cross section data on the simulated response
      of the HPA TLD.
AB  - The relative response of the new Health Protection Agency thermoluminescence
      dosimeter (TLD) has been calculated for Narrow Series X-ray distribution and
      (137)Cs photon sources using the Monte Carlo code MCNP5, and the results compared
      with those obtained during its design stage using the predecessor code, MCNP4c2.
      The results agreed at intermediate energies (approximately 0.1 MeV to (137)Cs),
      but differed at low energies (<0.1 MeV) by up to approximately 10%. This
      disparity has been ascribed to differences in the default photon interaction data
      used by the two codes, and derives ultimately from the effect on absorbed dose of
      the recent updates to the photoelectric cross sections. The sources of these data
      have been reviewed.

PMID- 19386776
TI  - Too much of a good thing?

PMID- 19386777
TI  - Analyses of conditions for KMSSS loop in tyrosyl-tRNA synthetase by building a
      mutant library.
AB  - The KMSKS motif is the ATP binding motif for aminoacylation process of class I
      aminoacyl-tRNA synthetases. Although researches based on natural proteins inform
      us about the contribution of natural amino acid sequences for the catalysis, they
      have difficulties in discussing the other alternative sequences and prohibited
      sequences for the motif to maintain the catalytic ability. In order to reveal
      such the conditions for the alternative and prohibited sequences, it is important
      to investigate a library of various mutants for the motif. For that purpose, we
      build a library of more than 200 mutants substituting the KMSSS loop, Lys204
      Met205-Ser206-Ser207-Ser208, in tyrosyl-tRNA synthetase of Methanococcus
      jannaschii, and their catalytic abilities were examined by the Amber suppression
      method. Mutants of K204R and K204N still maintained catalytic abilities to a
      certain extent. On the other hand, a variety of alternative sequences for Ser206
      Ser207-Ser208 were obtained, and some of those did not include either Ser or Thr,
      which were regarded as necessary residues in the KMSKS motif in previous works.
      In this article, catalytic activity of all the mutants are represented in detail
      and some suggestions for the condition of the motif are discussed.

PMID- 19386778
TI  - Fast binding kinetics and conserved 3D structure underlie the antagonistic
      activity of mutant TNF: useful information for designing artificial proteo
      antagonists.
AB  - Tumour necrosis factor (TNF) is an important cytokine that induces an
      inflammatory response predominantly through the TNF receptor-1 (TNFR1). A crucial
      strategy for the treatment of many autoimmune diseases, therefore, is to block
      the binding of TNF to TNFR1. We previously identified a TNFR1-selective
      antagonistic mutant TNF (R1antTNF) from a phage library containing six randomized
      amino acid residues at the receptor-binding site (amino acids 84-89). Two
      R1antTNFs, R1antTNF-T2 (A84S, V85T, S86T, Y87H, Q88N and T89Q) and R1antTNF-T8
      (A84T, V85P, S86A, Y87I, Q88N and T89R), were successfully isolated from this
      library. Here, we analysed R1antTNF-T8 using surface plasmon resonance
      spectroscopy and X-ray crystallography to determine the mechanism underlying the
      antagonistic activity of R1antTNF. The kinetic association/dissociation
      parameters of R1antTNF-T8 were higher than those of wild-type TNF, indicating
      more rapid bond dissociation. X-ray crystallographic analysis suggested that the
      binding mode of the T89R mutation changed from a hydrophobic to an electrostatic
      interaction, which may be responsible for the antagonistic behaviour of R1antTNF.
      Knowledge of these structure-function relationships will facilitate the design of
      novel TNF inhibitors based on the cytokine structure.

PMID- 19386779
TI  - A novel virtual spectrometry: Visualized regulatory motifs on ADM, rPol{beta} and
      CD83 mRNAs in human-friendly manners.
AB  - Recently, riboswitches and other structures discovered on mRNAs have been
      reported as examples of functional RNA structures, motifs. Such motifs were shown
      to be present as single-form valid structures but they are obscured among other
      less-valid structures. Here, I present a novel, practical virtual spectrometry
      (the GenoPoemics Spectrometry) visualizing motifs on mRNA strands as spectra at-a
      glance. Every motif along with validity of their existences could be observed on
      the spectra in human-friendly manners, and whole structures of mRNAs could be
      overviewed. Therefore, the spectra helped distinguish valid and less valid
      motifs. The spectrometry was applied to variety of mRNAs such as ADM, rPolbeta
      and CD83 to identify structures of high validity on them, previously reported
      functional motifs were successfully revealed. These findings indicate that the
      structures of mRNAs that may be folded into multiple forms can be further
      discussed quantitatively based on the visual spectra to discover functional RNA
      motifs.

PMID- 19386780
TI  - Analysis of Puumala hantavirus in a bank vole population in northern Finland:
      evidence for co-circulation of two genetic lineages and frequent reassortment
      between strains.
AB  - In this study, for the first time, two distinct genetic lineages of Puumala virus
      (PUUV) were found within a small sampling area and within a single host genetic
      lineage (Ural mtDNA) at Pallasjarvi, northern Finland. Lung tissue samples of 171
      bank voles (Myodes glareolus) trapped in September 1998 were screened for the
      presence of PUUV nucleocapsid antigen and 25 were found to be positive. Partial
      sequences of the PUUV small (S), medium (M) and large (L) genome segments were
      recovered from these samples using RT-PCR. Phylogenetic analysis revealed two
      genetic groups of PUUV sequences that belonged to the Finnish and north
      Scandinavian lineages. This presented a unique opportunity to study inter-lineage
      reassortment in PUUV; indeed, 32 % of the studied bank voles appeared to carry
      reassortant virus genomes. Thus, the frequency of inter-lineage reassortment in
      PUUV was comparable to that of intra-lineage reassortment observed previously
      (Razzauti, M., Plyusnina, A., Henttonen, H. & Plyusnin, A. (2008). J Gen Virol
      89, 1649-1660). Of six possible reassortant S/M/L combinations, only two were
      found at Pallasjarvi and, notably, in all reassortants, both S and L segments
      originated from the same genetic lineage, suggesting a non-random pattern for the
      reassortment. These findings are discussed in connection to PUUV evolution in
      Fennoscandia.

PMID- 19386781
TI  - In vitro biology of fibropapilloma-associated turtle herpesvirus and host cells
      in Hawaiian green turtles (Chelonia mydas).
AB  - Fibropapillomatosis (FP) of green turtles has a global distribution and causes
      debilitating tumours of the skin and internal organs in several species of marine
      turtles. FP is associated with a presently non-cultivable alphaherpesvirus
      Chelonid fibropapilloma-associated herpesvirus (CFPHV). Our aims were to employ
      quantitative PCR targeted to pol DNA of CFPHV to determine (i) if DNA sequesters
      by tumour size and/or cell type, (ii) whether subculturing of cells is a viable
      strategy for isolating CFPHV and (iii) whether CFPHV can be induced to a lytic
      growth cycle in vitro using chemical modulators of replication (CMRs),
      temperature variation or co-cultivation. Additional objectives included
      determining whether non-tumour and tumour cells behave differently in vitro and
      confirming the phenotype of cultured cells using cell-type-specific antigens.
      CFPHV pol DNA was preferentially concentrated in dermal fibroblasts of skin
      tumours and the amount of viral DNA per cell was independent of tumour size. Copy
      number of CFPHV pol DNA per cell rapidly decreased with cell doubling of tumour
      derived fibroblasts in culture. Attempts to induce viral replication in known
      CFPHV-DNA-positive cells using temperature or CMR failed. No significant
      differences were seen in in vitro morphology or growth characteristics of
      fibroblasts from tumour cells and paired normal skin, nor from CFPHV pol-DNA
      positive intestinal tumour cells. Tumour cells were confirmed as fibroblasts or
      keratinocytes by positive staining with anti-vimentin and anti-pancytokeratin
      antibodies, respectively. CFPHV continues to be refractory to in vitro
      cultivation.

PMID- 19386784
TI  - Characterization of seven novel human papillomavirus types isolated from
      cutaneous tissue, but also present in mucosal lesions.
AB  - Seven novel human papillomavirus (HPV) types were isolated and characterized. HPV
      94 is related most closely to HPV 10 and belongs to the genus
      Alphapapillomavirus, whereas HPV 98, HPV 99, HPV 100, HPV 104, HPV 105 and HPV
      113 all belong to the genus Betapapillomavirus. These HPV types were isolated
      from and demonstrated in cutaneous tissue, but HPV 98, HPV 100, HPV 104 and HPV
      113 were also detected in malignant oesophageal and oral lesions. The general
      prevalence of these HPV types in lesions is infrequent.

PMID- 19386783
TI  - Chlorella viruses prevent multiple infections by depolarizing the host membrane.
AB  - Previous experiments established that when the unicellular green alga Chlorella
      NC64A is inoculated with two viruses, usually only one virus replicates in a
      single cell. That is, the viruses mutually exclude one another. In the current
      study, we explore the possibility that virus-induced host membrane
      depolarization, at least partially caused by a virus-encoded K(+) channel (Kcv),
      is involved in this mutual exclusion. Two chlorella viruses, PBCV-1 and NY-2A,
      were chosen for the study because (i) they can be distinguished by real-time PCR
      and (ii) they exhibit differential sensitivity to Cs(+), a well-known K(+)
      channel blocker. PBCV-1-induced host membrane depolarization, Kcv channel
      activity and plaque formation are only slightly affected by Cs(+), whereas all
      three NY-2A-induced events are strongly inhibited by Cs(+). The addition of one
      virus 5-15 min before the other results primarily in replication of the first
      virus. However, if virus NY-2A-induced membrane depolarization of the host is
      blocked by Cs(+), PBCV-1 is not excluded. We conclude that virus-induced membrane
      depolarization is at least partially responsible for the exclusion phenomenon.

PMID- 19386782
TI  - Antibody responses to 26 skin human papillomavirus types in the Netherlands,
      Italy and Australia.
AB  - Solar UV radiation is the main risk factor for cutaneous squamous cell carcinoma
      (SCC), but infections with skin human papillomavirus (HPV) types have also been
      linked to the development of SCC. Little is known about the natural history of
      these infections and whether the seroprevalence of skin HPV types is affected by
      ambient or individual levels of sun exposure. This study investigated this by
      analysing sera for antibodies to 26 skin HPV types from five phylogenetic genera
      obtained from 807 healthy individuals from the Netherlands, Italy and Australia,
      countries with strong differences in sunlight intensity. Overall HPV
      seroprevalence was similar across the three countries (50-57 % for beta-HPV
      types, 40-48 % for gamma-HPV types), and the most frequent beta-HPV and gamma-HPV
      types were the same in all countries. The highest seroprevalences for 24 of the
      26 skin HPV types were observed in Italy (14 types) and Australia (ten types).
      Seroprevalence among men was generally higher than among women, and the male sex
      was significantly associated with both beta-HPV [odds ratio (OR) 2.81, 95 %
      confidence interval (CI) 1.64-4.82] and gamma-HPV (OR 2.42, 95 % CI 1.40-4.18)
      antibodies in Australia. The only measure of sun sensitivity or UV exposure
      significantly associated with skin HPV seroprevalence was found for weekend sun
      exposure in Australia and beta-HPV antibodies. It was concluded that type spectra
      and HPV seroprevalence are similar in countries with different sunlight
      intensity, and that levels of UV exposure do not play a strong role in the
      development of skin HPV antibodies in this study population.

PMID- 19386785
TI  - Formulation of bovine respiratory syncytial virus fusion protein with CpG
      oligodeoxynucleotide, cationic host defence peptide and polyphosphazene enhances
      humoral and cellular responses and induces a protective type 1 immune response in
      mice.
AB  - Respiratory syncytial virus (RSV) is the leading cause of serious respiratory
      tract disease in children and calves; however, RSV vaccine development has been
      slow due to early observations that formalin-inactivated vaccines induced Th2
      type immune responses and led to disease enhancement upon subsequent exposure.
      Hence, there is a need for novel adjuvants that will promote a protective Th1
      type or balanced immune response against RSV. CpG oligodeoxynucleotides (ODNs),
      indolicidin, and polyphosphazene were examined for their ability to enhance
      antigen-specific immune responses and influence the Th-bias when co-formulated
      with a recombinant truncated bovine RSV (BRSV) fusion protein (DeltaF). Mice
      immunized with DeltaF co-formulated with CpG ODN, indolicidin, and
      polyphosphazene (DeltaF/CpG/indol/PP) developed higher levels of DeltaF-specific
      serum IgG, IgG1 and IgG2a antibodies when compared with DeltaF alone, and
      displayed an increase in the frequency of gamma interferon-secreting cells and
      decreased interleukin (IL)-5 production by in vitro restimulated splenocytes,
      characteristic of a Th1 immune response. These results were observed in both
      C57BL/6 and BALB/c strains of mice. When evaluated in a BRSV challenge model,
      mice immunized with DeltaF/CpG/indol/PP developed significantly higher levels of
      BRSV-neutralizing serum antibodies than mice immunized with the DeltaF protein
      alone, and displayed significantly less pulmonary IL-4, IL-5, IL-13 and eotaxin
      and reduced eosinophilia after challenge. These results suggest that co
      formulation of DeltaF with CpG ODN, host defence peptide and polyphosphazene may
      result in a safe and effective vaccine for the prevention of BRSV and may have
      implications for the development of novel human RSV vaccines.

PMID- 19386786
TI  - Comparison of 12 turkey hemorrhagic enteritis virus isolates allows prediction of
      genetic factors affecting virulence.
AB  - Turkey hemorrhagic enteritis virus (THEV) is a member of the genus Siadenovirus
      and causes disease in turkey poults characterized by splenomegaly, bloody
      diarrhoea and death. The mechanism responsible for intestinal lesion formation
      and mortality is not known, although there is strong evidence that it is immune
      mediated. All strains of THEV are serologically indistinguishable, although there
      are naturally occurring avirulent strains of THEV that replicate efficiently in
      turkeys without the intestinal haemorrhage or mortality associated with more
      virulent strains. The purpose of this study was to determine which viral genes
      are involved in virulence. The full-length genome of an avirulent vaccine strain
      was sequenced and compared with the genome of a virulent field isolate from
      Israel that was sequenced in 1998. Comparison of the two 26.3 kb genomes revealed
      49 nucleotide differences resulting in 14 putative amino acid changes within
      viral proteins. Sequencing of the regions surrounding the 14 missense mutations
      revealed variations in ORF1, E3 and the fiber (fib) knob domain in five
      additional strains with varying degrees of virulence. Complete sequences of these
      genes were determined in a total of 11 different strains of THEV. All strains had
      at least one missense mutation in ORF1, and all but two of the strains had one
      missense mutation in E3. At least one missense mutation was found in the fiber
      knob domain in six out of seven virulent strains. Sequence variation of ORF1, E3
      and fib in strains of THEV with different phenotypes strongly indicates that
      these genes are the key factors affecting virulence.

PMID- 19386787
TI  - Cystic fibrosis transmembrane conductance regulator and caveolin-1 regulate
      epithelial cell internalization of Pseudomonas aeruginosa.
AB  - Patients with cystic fibrosis (CF) exhibit defective innate immunity and are
      susceptible to chronic lung infection with Pseudomonas aeruginosa. To investigate
      the molecular bases for the hypersusceptibility of CF patients to P. aeruginosa,
      we used the IB3-1 cell line with two defective CF transmembrane conductance
      regulator (CFTR) genes (DeltaF508/W1282X) to generate isogenic stable, clonal
      lung epithelial cells expressing wild-type (WT)-CFTR with an NH(2)-terminal green
      fluorescent protein (GFP) tag. GFP-CFTR exhibited posttranslational modification,
      subcellular localization, and anion transport function typical of WT-CFTR. P.
      aeruginosa internalization, a component of effective innate immunity, required
      functional CFTR and caveolin-1, as shown by: 1) direct correlation between GFP
      CFTR expression levels and P. aeruginosa internalization; 2) enhanced P.
      aeruginosa internalization by aminoglycoside-induced read through of the CFTR
      W1282X allele in IB3-1 cells; 3) decreased P. aeruginosa internalization
      following siRNA knockdown of GFP-CFTR or caveolin-1; and 4) spatial association
      of P. aeruginosa with GFP-CFTR and caveolin-1 at the cell surface. P. aeruginosa
      internalization also required free lateral diffusion of GFP-CFTR, allowing for
      bacterial coclustering with GFP-CFTR and caveolin-1 at the plasma membrane. Thus
      efficient initiation of innate immunity to P. aeruginosa requires formation of an
      epithelial "internalization platform" involving both caveolin-1 and functional,
      laterally mobile CFTR.

PMID- 19386788
TI  - Endofacial competitive inhibition of the glucose transporter 1 activity by
      gossypol.
AB  - Gossypol is a natural disesquiterpene that blocks the activity of the mammalian
      facilitative hexose transporter GLUT1. In human HL-60 cells, which express GLUT1,
      Chinese hamster ovary cells overexpressing GLUT1, and human erythrocytes,
      gossypol inhibited hexose transport in a concentration-dependent fashion,
      indicating that blocking of GLUT1 activity is independent of cellular context.
      With the exception of red blood cells, the inhibition of cellular transport was
      instantaneous. Gossypol effect was specific for the GLUT1 transporter since it
      did not alter the uptake of nicotinamide by human erythrocytes. Gossypol affects
      the glucose-displaceable binding of cytochalasin B to GLUT1 in human erythrocyte
      ghost in a mixed noncompetitive way, with a K(i) value of 20 microM. Likewise,
      GLUT1 fluorescence was quenched approximately 80% by gossypol, while Stern-Volmer
      plots for quenching by iodide displayed increased slopes by gossypol addition.
      These effects on protein fluorescence were saturable and unaffected by the
      presence of D-glucose. Gossypol did not alter the affinity of D-glucose for the
      external substrate site on GLUT1. Kinetic analysis of transport revealed that
      gossypol behaves as a noncompetitive inhibitor of zero-trans (substrate outside
      but not inside) transport, but it acts as a competitive inhibitor of equilibrium
      exchange (substrate inside and outside) transport, which is consistent with
      interaction at the endofacial surface, but not at the exofacial surface of the
      transporter. Thus, gossypol behaves as a quasi-competitive inhibitor of GLUT1
      transport activity by binding to a site accessible through the internal face of
      the transporter, but it does not, in fact, compete with cytochalasin B binding.
      Our observations suggest that some effects of gossypol on cellular physiology may
      be related to its ability to disrupt the normal hexose flux through GLUT1, a
      transporter expressed in almost every kind of mammalian cell and responsible for
      the basal uptake of glucose.

PMID- 19386789
TI  - Satellite cell-mediated angiogenesis in vitro coincides with a functional hypoxia
      inducible factor pathway.
AB  - Muscle regeneration involves the coordination of myogenesis and revascularization
      to restore proper muscle function. Myogenesis is driven by resident stem cells
      termed satellite cells (SC), whereas angiogenesis arises from endothelial cells
      and perivascular cells of preexisting vascular segments and the collateral
      vasculature. Communication between myogenic and angiogenic cells seems plausible,
      especially given the number of growth factors produced by SC. To characterize
      these interactions, we developed an in vitro coculture model composed of rat
      skeletal muscle SC and microvascular fragments (MVF). In this system, isolated
      epididymal MVF suspended in collagen gel are cultured over a rat SC monolayer
      culture. In the presence of SC, MVF exhibit greater indices of angiogenesis than
      MVF cultured alone. A positive dose-dependent effect of SC conditioned medium
      (CM) on MVF growth was observed, suggesting that SC secrete soluble-acting growth
      factor(s). Next, we specifically blocked VEGF action in SC CM, and this was
      sufficient to abolish satellite cell-induced angiogenesis. Finally, hypoxia
      inducible factor-1alpha (HIF-1alpha), a transcriptional regulator of VEGF gene
      expression, was found to be expressed in cultured SC and in putative SC in
      sections of in vivo stretch-injured rat muscle. Hypoxic culture conditions
      increased SC HIF-1alpha activity, which was positively associated with SC VEGF
      gene expression and protein levels. Collectively, these initial observations
      suggest that a heretofore unexplored aspect of satellite cell physiology is the
      initiation of a proangiogenic program.

PMID- 19386790
TI  - Introgression of apomixis into sexual species is inhibited by mentor effects and
      ploidy barriers in the Ranunculus auricomus complex.
AB  - BACKGROUND AND AIMS: Apomictic plants maintain functional pollen, and via
      pollination the genetic factors controlling apomixis can be potentially
      transferred to congeneric sexual populations. In contrast, the sexual individuals
      do not fertilize apomictic plants which produce seeds without fertilization of
      the egg cells. This unidirectional introgressive hybridization is expected
      finally to replace sexuality by apomixis and is thought to be a causal factor for
      the wide geographical distribution of apomictic complexes. Nevertheless, this
      process may be inhibited by induced selfing (mentor effects) of otherwise self
      incompatible sexual individuals. Here whether mentor effects or actual cross
      fertilization takes place between diploid sexual and polyploid apomictic
      cytotypes in the Ranunculus auricomus complex was tested via experimental
      crosses. METHODS: Diploid sexual mother plants were pollinated with tetra- and
      hexaploid apomictic pollen donators by hand, and the amount of well-developed
      seed compared with aborted seed was evaluated. The reproductive pathways were
      assessed in the well-developed seed via flow cytometric seed screen (FCSS). KEY
      RESULTS: The majority of seed was aborted; the well-developed seeds have resulted
      from both mentor effects and cross-fertilization at very low frequencies (1.3 and
      1.6 % of achenes, respectively). Pollination by 4x apomictic pollen plants
      results more frequently in cross-fertilization, whereas pollen from 6x plants
      more frequently induced mentor effects. CONCLUSIONS: It is concluded that
      introgression of apomixis into sexual populations is limited by ploidy barriers
      in the R. auricomus complex, and to a minor extent by mentor effects. In mixed
      populations, sexuality cannot be replaced by apomixis because the higher
      fertility of sexual populations still compensates the low frequencies of
      potential introgression of apomixis.

PMID- 19386792
TI  - Mechanism-based pharmacokinetic/pharmacodynamic model of parathyroid hormone
      calcium homeostasis in rats and humans.
AB  - The purpose of this study was to develop a mechanism-based
      pharmacokinetic/pharmacodynamic model that describes the regulation of the
      parathyroid hormone (PTH)-Ca(2+) system in rats and humans. Temporal
      concentration data for endogenous PTH and Ca(2+) were extracted from literature
      for rats (normal adult males) and humans. In addition, exogenous PTH was
      administered subcutaneously to male Sprague-Dawley rats with jugular vein
      catheters, and plasma concentrations were measured over time. A mathematical
      model was developed and fitted simultaneously to endogenous PTH, Ca(2+), and
      exogenous PTH concentrations in rats. Ca(2+) concentrations were described using
      a turnover model, with its depletion being induced by a chelating agent, and PTH
      concentrations were characterized using a precursor-dependent indirect response
      model. The same structural model was used for fitting data obtained in humans.
      PTH stimulation was driven by occupancy of the Ca(2+) sensing receptor, and
      lowering of physiological Ca(2+) concentrations increased PTH secretion, with PTH
      profiles being adequately described by the model. PTH stimulatory capacity was
      baseline-dependent in rats [S(max_rats) = 34.8 x PTH(0)] and humans
      [S(max_humans) = 392/PTH(0)]. Modeling results suggest that normal rats are twice
      as sensitive to Ca(2+)-induced PTH stimulation compared with humans. In
      conclusion, the developed model adequately characterizes the PTH-Ca(2+)
      regulation across species and may be useful in the development of therapeutic
      drugs targeting this system.

PMID- 19386791
TI  - Overexpression of peroxiredoxin 6 does not prevent ethanol-mediated oxidative
      stress and may play a role in hepatic lipid accumulation.
AB  - Oxidative stress is implicated in the etiology of many diseases, including
      alcoholic liver disease (ALD). Peroxiredoxin 6 is a cytosolic peroxidase that has
      been demonstrated to protect various tissues, such as skin, lung, and cardiac
      muscle, against acute oxidative insults. Consequently, peroxiredoxin 6 was
      hypothesized to also protect the liver from oxidative stress generated during the
      process of chronic ethanol ingestion. To test this, wild-type peroxiredoxin 6
      knockout mice (KO), and transgenic peroxiredoxin 6 overexpressing mice (TG) were
      fed an ethanol-containing diet. Various biomarkers of ALD were assessed, along
      with the effects of chronic ethanol consumption on the antioxidant defenses.
      After 9 weeks of ethanol consumption, all backgrounds exhibited elevations of
      plasma alanine aminotransferase activity, hepatosteatosis, CYP2E1 induction, and
      lipid peroxidation; however, hepatic triglyceride accumulation seemed to be
      exacerbated in ethanol-fed TG mice. Differences in antioxidant protein expression
      and activity in response to chronic ethanol consumption were also observed.
      Examples include significant inductions of catalase and glutathione transferase
      activity in ethanol-fed KO and TG mice, along with elevated levels of glutathione
      peroxidase activity. These alterations in antioxidant defenses could be
      attributed to either compensatory responses due to the genetic manipulations or
      ethanol-mediated responses. In conclusion, both ethanol-fed KO and ethanol-fed TG
      mice developed early stage ALD and peroxiredoxin 6 may play a role in ethanol
      mediated hepatic lipid accumulation.

PMID- 19386793
TI  - Effects of roflumilast, a phosphodiesterase-4 inhibitor, on hypoxia- and
      monocrotaline-induced pulmonary hypertension in rats.
AB  - Phosphodiesterase type 4 (PDE4) is involved in the hydrolysis of cAMP in
      pulmonary vascular smooth muscle (PA-SMC) and immune inflammatory cells. Given
      that intracellular cAMP accumulation inhibits contraction and growth of PA-SMCs
      as well as inflammatory cell functions, we investigated the effects of the PDE4
      inhibitor 3-cyclopropylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]
      benzamide (roflumilast), on pulmonary hypertension (PH) in rats. Treatment with
      roflumilast (0.5 or 1.5 mg x kg(-1) day(-1)) from day 1 to day 21 after
      monocrotaline (MCT) injection (60 mg x kg(-1) s.c.) attenuated PH development:
      pulmonary artery pressure, right ventricular hypertrophy, and muscularization of
      distal vessels on day 21 were decreased compared to control MCT-treated rats.
      Roflumilast (1.5 mg x kg(-1) day(-1)) also reduced the increases in interleukin-6
      and monocyte chemotactic protein-1 mRNAs observed in lung tissue on day 21
      without affecting the rise in interleukin-1beta mRNA on days 1 and 21.
      Roflumilast (1.5 mg x kg(-1) day(-1)) from day 21 to day 42 after MCT reversed
      established PH, almost normalizing pulmonary artery pressure and structure, and
      suppressing proliferating cell nuclear antigen-positive cells in pulmonary
      vascular walls. Treatment with roflumilast similarly attenuated PH development
      due to chronic hypoxia. Treatment of human PA-SMCs with roflumilast N-oxide, the
      active metabolite of roflumilast, at concentrations up to 10(-6) M, potentiated
      PA-SMC growth inhibition induced by prostacyclin (10(-6) M) or interleukin-1beta
      (10 ng x ml(-1)) but was inactive on its own. In conclusion, the PDE4 inhibitor
      roflumilast significantly attenuates pulmonary vascular remodeling and
      hypertension induced by chronic hypoxia or MCT and reverses established PH after
      MCT administration.

PMID- 19386794
TI  - Comparison of the effect of two driving retraining programs on on-road
      performance after stroke.
AB  - BACKGROUND: Several driving retraining programs have been developed to improve
      driving skills after stroke. Those programs rely on different rehabilitation
      concepts. OBJECTIVES: The current study sought to examine the specific carryover
      effect of driving skills of a comprehensive training program in a driving
      simulator when compared with a cognitive training program. METHODS: Further
      analysis from a previous randomized controlled trial that investigated the effect
      of simulator training on driving after stroke. Forty-two participants received
      simulator-based driving training, whereas 41 participants received cognitive
      training for 15 hours. Overall performance in the on-road test and each of its 13
      items were compared between groups immediately posttraining and at 6 months
      poststroke. RESULTS: Generalized estimating equation analysis showed that the
      total score on the on-road test and each item score improved significantly over
      time for both groups. Those who received driving simulator training achieved
      better results when compared with the cognitive training group in the overall on
      road score and the items of anticipation and perception of signs, visual behavior
      and communication, quality of traffic participation, and turning left. Most of
      the differences in improvement between the 2 interventions were observed at 6
      months poststroke. CONCLUSIONS: Contextual training in a driving simulator
      appeared to be superior to cognitive training to treat impaired on-road driving
      skills after stroke. The effects were primarily seen in visuointegrative driving
      skills. Our results favor the implementation of driving simulator therapy in the
      conventional rehabilitation program of subacute stroke patients with mild
      deficits.

PMID- 19386795
TI  - Evaluation of a novel therapeutic approach to treating severe pneumococcal
      infection using a mouse model.
AB  - P4, a 28-amino-acid peptide, is a eukaryotic cellular activator that enhances
      specific in vitro opsonophagocytic killing of multiple bacterial pathogens. In a
      previous study, we successfully recreated this phenomenon in mice in vivo by
      using a two-dose regimen of P4 and pathogen-specific antibodies, which
      significantly reduced moribundity in mice. For the present study, we hypothesized
      that the inclusion of a low-dose antibiotic would make it possible to treat the
      infected mice with a single dose containing a mixture of P4 and a pathogen
      specific antibody. A single dose consisting of P4, intravenous immunoglobulin
      (IVIG), and ceftriaxone effectively reduced moribundity compared to that of
      untreated controls (n = 10) by 75% (P < 0.05) and rescued all (10 of 10) infected
      animals (P < 0.05). If rescued animals were reinfected with Streptococcus
      pneumoniae and treated with a single dose containing P4, IVIG, and ceftriaxone,
      they could be rerescued. This observation of the repeated successful use of P4
      combination therapy demonstrates a low risk of tolerance development.
      Additionally, we examined the polymorphonuclear leukocytes (PMN) derived from
      infected mice and observed that P4 enhanced in vitro opsonophagocytic killing (by
      >80% over the control level; P < 0.05). This finding supports our hypothesis that
      PMN are activated by P4 during opsonophagocytosis and the recovery of mice from
      pneumococcal infection. P4 peptide-based combination therapy may offer an
      alternative and rapid immunotherapy to treat fulminant pneumococcal infection.

PMID- 19386796
TI  - Evaluation of a commercial blocking enzyme-linked immunosorbent assay to detect
      avian influenza virus antibodies in multiple experimentally infected avian
      species.
AB  - Wild birds of the orders Anseriformes and Charadriiformes are the natural
      reservoirs for avian influenza (AI) viruses. Traditionally, AI virus surveillance
      in wild birds has relied on virus identification strategies, including virus
      isolation and detection. To evaluate the accuracy of a commercial blocking enzyme
      linked immunosorbent assay (bELISA) and the agar gel immunodiffusion (AGID) test
      for detection of antibodies in wild birds, which is indicative of AI virus
      infection, we tested 281 serum samples from various wild avian species that were
      experimentally infected with AI viruses. Included in these samples were 178
      samples from birds with confirmed AI virus infections (122 infected with low
      pathogenic AI [LPAI] viruses and 56 infected with highly pathogenic AI [HPAI]
      viruses) and 103 samples from birds that were uninfected, negative controls. The
      sensitivities of the bELISA and the AGID test were 0.820 (95% confidence interval
      [95% CI], 0.756 to 0.874) and 0.674 (95% CI, 0.600 to 0.742), respectively. Both
      tests had an estimated specificity of 1.00 (95% CI, 0.965 to 1.00). The bELISA
      was significantly more sensitive than the AGID test for both LPAI virus- and HPAI
      virus-infected birds. Both assays, however, had a higher sensitivity for birds
      infected with HPAI virus than for birds infected with LPAI virus. These results
      demonstrate the potential utility of the bELISA for detection of antibodies to
      both LPAI and HPAI viruses in multiple avian species, representing five avian
      orders and 17 genera. Additional studies are warranted to further evaluate the
      utility of the bELISA for use with naturally infected birds.

PMID- 19386797
TI  - Altered ex vivo expression of caspase 8, caspase 9, and Bcl-2 is associated with
      T-cell hyporeactivity in patients with paracoccidioidomycosis.
AB  - To better understand the T-cell hyporesponsiveness of patients with
      paracoccidioidomycosis, we tested the hypothesis that the T cells were committed
      to apoptosis. We show here that T cells of patients with paracoccidioidomycosis
      overexpress caspase 9 and caspase 8 but express low Bcl-2 levels and that
      interleukin-2 was unable to revert the hyporesponsiveness. These data suggest
      that the T cells would in vivo be driven to a tolerant state and apoptosis.

PMID- 19386798
TI  - Relevance of gamma interferon, tumor necrosis factor alpha, and interleukin-10
      gene polymorphisms to susceptibility to Mediterranean spotted fever.
AB  - The acute phase of Mediterranean spotted fever (MSF) is characterized by dramatic
      changes in cytokine production patterns, clearly indicating their role in the
      immunomodulation of the response against the microorganism, and the differences
      in cytokine production seem to influence the extent and severity of the disease.
      In this study, the single nucleotide polymorphisms (SNPs) of tumor necrosis
      factor alpha (TNF-alpha) -308G/A (rs1800629) and interleukin-10 (IL-10) -1087G/A
      (rs1800896), -824C/T (rs1800871), and -597C/A (rs1800872) and the gamma
      interferon (IFN-gamma) T/A SNP at position +874 (rs2430561) were typed in 80
      Sicilian patients affected by MSF and in 288 control subjects matched for age,
      gender, and geographic origin. No significant differences in TNF-alpha -308G/A
      genotype frequencies were observed. The +874TT genotype, associated with an
      increased production of IFN-gamma, was found to be significantly less frequent in
      MSF patients than in the control group (odds ratio [OR], 0.18; 95% confidence
      interval [95% CI], 0.06 to 0.51; P corrected for the number of genotypes [Pc],
      0.0021). In addition, when evaluating the IFN-gamma and IL-10 genotype
      interaction, a significant increase of +874AA/-597CA (OR, 5.31; 95% CI, 2.37 to
      11.88; P(c), 0.0027) combined genotypes was observed. In conclusion, our data
      strongly suggest that finely genetically tuned cytokine production may play a
      crucial role in the regulation of the immune response against rickettsial
      infection, therefore influencing the disease outcomes, ranging from nonapparent
      or subclinical condition to overt or fatal disease.

PMID- 19386799
TI  - Identification of secreted antigen 3 from Babesia gibsoni.
AB  - A cDNA expression library of Babesia gibsoni was screened with the serum
      collected from a dog experimentally infected with B. gibsoni. A novel antigen
      sharing homology with secreted antigen 1 of B. gibsoni was isolated. The genomic
      analysis indicated that the BgSA3 gene exists as multicopies in the genome of B.
      gibsoni. The putative peptide encoded by the BgSA3 gene showed some
      characteristics of secreted proteins. The serum raised in mice immunized with the
      recombinant BgSA3 expressed in Escherichia coli could recognize a native parasite
      protein with a molecular mass of 70 kDa. Moreover, a sandwich enzyme-linked
      immunosorbent assay with anti-BgSA3 antibodies could detect the circulating BgSA3
      in the blood plasma of dogs experimentally infected with B. gibsoni. The
      identification of BgSA3 provided a useful target for the development of a
      diagnostic test for detecting specific antibodies and circulating antigens.

PMID- 19386800
TI  - Serological diagnosis of Brucella infections in odontocetes.
AB  - Brucella ceti causes disease in Odontoceti. The absence of control serum
      collections and the diversity of cetaceans have hampered the standardization of
      serological tests for the diagnosis of cetacean brucellosis. Without a "gold"
      standard for sensitivity and specificity determination, an alternative approach
      was followed. We designed an indirect enzyme-linked immunosorbent assay (iELISA)
      that recognizes immunoglobulins G (IgGs) from 17 odontocete species as a single
      group. For the standardization, we used Brucella melitensis and Brucella abortus
      lipopolysaccharides, serum samples from seven resident odontocetes with no
      history of infectious disease displaying negative rose bengal test (RBT)
      reactions, and serum samples from seven dolphins infected with B. ceti. We
      compared the performance of the iELISA with those of the protein G ELISA
      (gELISA), the competitive ELISA (cELISA), and the immunofluorescence (IF) and dot
      blot (DB) tests, using 179 odontocete serum samples and RBT as the reference. The
      diagnostic potential based on sensitivity and specificity of the iELISA was
      superior to that of gELISA and cELISA. The correlation and agreement between the
      iELISA and the gELISA were relatively good (R(i/g)2 = 0.65 and kappa(i/g) = 0.66,
      respectively), while the correlation and agreement of these two ELISAs with
      cELISA were low (R(i/c)2 = 0.46, R(g/c)2 = 0.37 and kappa(i/c) = 0.62, kappa(g/c)
      = 0.42). In spite of using the same anti-odontocete IgG antibody, the iELISA was
      more specific than were the IF and DB tests. An association between high antibody
      titers and the presence of neurological symptoms in dolphins was observed. The
      prediction is that iELISA based on broadly cross-reacting anti-dolphin IgG
      antibody would be a reliable test for the diagnosis of brucellosis in
      odontocetes, including families not covered in this study.

PMID- 19386801
TI  - Interleukin-12 is the optimum cytokine to expand human Th17 cells in vitro.
AB  - Recently, a new lineage of CD4+ T cells in humans and in mice has been reported.
      This T helper cell secretes interleukin-17 (IL-17) and has been defined as T
      helper 17 (Th17). Th17 cells express the IL-23 receptor (IL-23R) and play an
      important pathogenic role in different inflammatory conditions. In this study,
      our aim was to characterize the optimum conditions for isolation and propagation
      of human peripheral blood Th17 cells in vitro and the optimum conditions for
      isolation of Th17 clones. To isolate Th17 cells, two steps were taken. Initially,
      we negatively isolated CD4+ T cells from peripheral blood mononuclear cells of a
      normal human blood donor. Then, we isolated the IL-23R+ cells from the CD4+ T
      cells. Functional studies revealed that CD4+ IL-23R+ cells could be stimulated ex
      vivo with anti-CD3/CD28 to secrete both IL-17 and gamma interferon (IFN-gamma).
      Furthermore, we expanded the CD4+ IL-23R+ cells for 1 week in the presence of
      anti-CD3/CD28, irradiated autologous feeder cells, and different cytokines. Our
      data indicate that cytokine treatment increased the number of propagated cells 14
      to 99-fold. Functional evaluation of the expanded number of CD4+ IL-23R+ cells
      in the presence of different cytokines with anti-CD3/CD28 revealed that all
      cytokines used (IL-2, IL-7, IL-12, IL-15, and IL-23) increased the amount of IFN
      gamma secreted by IL-23R+ CD4+ cells at different levels. Our results indicate
      that IL-7 plus IL-12 was the optimum combination of cytokines for the expansion
      of IL-23R+ CD4+ cells and the secretion of IFN-gamma, while IL-12 preferentially
      stimulated these cells to secrete predominately IL-17.

PMID- 19386802
TI  - Gene expression of nucleic acid-sensing pattern recognition receptors in children
      hospitalized for respiratory syncytial virus-associated acute bronchiolitis.
AB  - Given the critical role of pattern recognition receptors (PRRs) in acid nucleic
      recognition in the initiation of innate immunity and the orchestration of
      adaptive immunity, the aim of this study was to determine whether any
      heterogeneity of PRR expression in the airway tracts of infants with respiratory
      syncytial virus (RSV) infection might explain the broad clinical spectrum of RSV
      associated bronchiolitis in infants. For this purpose, the levels of melanoma
      differentiation-associated protein-5 (MDA-5), retinoic acid inducible gene-1 (RIG
      1), and Toll-like receptor 3 (TLR-3), TLR-7, TLR-8, and TLR-9 mRNAs were
      evaluated, using TaqMan quantitative reverse transcription-PCR, in cells from
      nasopharyngeal washes collected from 157 infants suffering from acute
      bronchiolitis whether or not they were associated with respiratory viruses. High
      interindividual variability was observed in both virus-positive and -negative
      infants; however, the relative gene expression levels of MDA-5, RIG-1, TLR-7, and
      TLR-8 were significantly higher in the virus-infected group, whereas the
      expression levels of TLR-3 and TLR-9 were not significantly different. The
      differences in the gene expression of MDA-5, RIG-1, TLR-7, and TLR-8 were more
      evident in infants with RSV infection than in those with bocavirus or rhinovirus
      infection. In RSV-infected infants, PRR-mRNA levels also were analyzed in
      relation to interferon protein levels, viral load, clinical severity, days of
      hospitalization, age, and body weight. A significant positive correlation was
      observed only between RSV viral load and RIG-1 mRNA levels. These findings
      provide the first direct evidence that, in infants with respiratory virus
      associated bronchiolitis, especially RSV, there are substantial changes in PRR
      gene expression; this likely is an important determinant of the clinical outcome
      of bronchiolitis.

PMID- 19386803
TI  - Two cys or not two cys? That is the question; alternative oxidase in the
      thermogenic plant sacred Lotus.
AB  - Sacred lotus (Nelumbo nucifera) regulates temperature in its floral chamber to 32
      degrees C to 35 degrees C across ambient temperatures of 8 degrees C to 40
      degrees C with heating achieved through high alternative pathway fluxes. In most
      alternative oxidase (AOX) isoforms, two cysteine residues, Cys(1) and Cys(2), are
      highly conserved and play a role in posttranslational regulation of AOX. Further
      control occurs via interaction of reduced Cys(1) with alpha-keto acids, such as
      pyruvate. Here, we report on the in vitro regulation of AOX isolated from
      thermogenic receptacle tissues of sacred lotus. AOX protein was mostly present in
      the reduced form, and only a small fraction could be oxidized with diamide.
      Cyanide-resistant respiration in isolated mitochondria was stimulated 4-fold by
      succinate but not pyruvate or glyoxylate. Insensitivity of the alternative
      pathway of respiration to pyruvate and the inability of AOX protein to be
      oxidized by diamide suggested that AOX in these tissues may lack Cys(1).
      Subsequently, we isolated two novel cDNAs for AOX from thermogenic tissues of
      sacred lotus, designated as NnAOX1a and NnAOX1b. Deduced amino acid sequences of
      both confirmed that Cys(1) had been replaced by serine; however, Cys(2) was
      present. This contrasts with AOXs from thermogenic Aroids, which contain both
      Cys(1) and Cys(2). An additional cysteine was present at position 193 in NnAOX1b.
      The significance of the sequence data for regulation of the AOX protein in
      thermogenic sacred lotus is discussed and compared with AOXs from other
      thermogenic and nonthermogenic species.

PMID- 19386804
TI  - Auxin-responsive genes AIR12 code for a new family of plasma membrane b-type
      cytochromes specific to flowering plants.
AB  - We report here on the identification of the major plasma membrane (PM) ascorbate
      reducible b-type cytochrome of bean (Phaseolus vulgaris) and soybean (Glycine
      max) hypocotyls as orthologs of Arabidopsis (Arabidopsis thaliana) AIR12 (for
      auxin induced in root cultures). Soybean AIR12, which is glycosylated and
      glycosylphosphatidylinositol-anchored to the external side of the PM in vivo, was
      expressed in Pichia pastoris in a recombinant form, lacking the
      glycosylphosphatidylinositol modification signal and purified from the culture
      medium. Recombinant AIR12 is a soluble protein predicted to fold into a beta
      sandwich domain and belonging to the DOMON (for dopamine beta-monooxygenase N
      terminus) domain superfamily. It is shown to be a b-type cytochrome with a
      symmetrical alpha-band at 561 nm, fully reduced by ascorbate, and fully oxidized
      by monodehydroascorbate radical. AIR12 is a high-potential cytochrome b showing a
      wide bimodal dependence from the redox potential between +80 mV and +300 mV.
      Optical absorption and electron paramagnetic resonance analysis indicate that
      AIR12 binds a single, highly axial low-spin heme, likely coordinated by
      methionine-91 and histidine-76, which are strongly conserved in AIR12 sequences.
      Phylogenetic analyses reveal that the auxin-responsive genes AIR12 represent a
      new family of PM b-type cytochromes specific to flowering plants. Circumstantial
      evidence suggests that AIR12 may interact with other redox partners within the PM
      to constitute a redox link between cytoplasm and apoplast.

PMID- 19386805
TI  - Reactive oxygen species are involved in brassinosteroid-induced stress tolerance
      in cucumber.
AB  - Brassinosteroids (BRs) induce plant tolerance to a wide spectrum of stresses. To
      study how BR induces stress tolerance, we manipulated the BR levels in cucumber
      (Cucumis sativus) through a chemical genetics approach and found that BR levels
      were positively correlated with the tolerance to photo-oxidative and cold
      stresses and resistance to Cucumber mosaic virus. We also showed that BR
      treatment enhanced NADPH oxidase activity and elevated H(2)O(2) levels in
      apoplast. H(2)O(2) levels were elevated as early as 3 h and returned to basal
      levels 3 d after BR treatment. BR-induced H(2)O(2) accumulation was accompanied
      by increased tolerance to oxidative stress. Inhibition of NADPH oxidase and
      chemical scavenging of H(2)O(2) reduced BR-induced oxidative and cold tolerance
      and defense gene expression. BR treatment induced expression of both regulatory
      genes, such as RBOH, MAPK1, and MAPK3, and genes involved in defense and
      antioxidant responses. These results strongly suggest that elevated H(2)O(2)
      levels resulting from enhanced NADPH oxidase activity are involved in the BR
      induced stress tolerance.

PMID- 19386806
TI  - Anatomical and transcriptomic studies of the coleorhiza reveal the importance of
      this tissue in regulating dormancy in barley.
AB  - The decay of seed dormancy during after-ripening is not well understood, but
      elucidation of the mechanisms involved may be important for developing strategies
      for modifying dormancy in crop species and, for example, addressing the problem
      of preharvest sprouting in cereals. We have studied the germination
      characteristics of barley (Hordeum vulgare 'Betzes') embryos, including a
      description of anatomical changes in the coleorhiza and the enclosed seminal
      roots. The changes that occur correlate with abscisic acid (ABA) contents of
      embryo tissues. To understand the molecular mechanisms involved in dormancy loss,
      we compared the transcriptome of dormant and after-ripened barley embryos using a
      tissue-specific microarray approach. Our results indicate that in the coleorhiza,
      ABA catabolism is promoted and ABA sensitivity is reduced and that this is
      associated with differential regulation by after-ripening of ABA 8'-hydroxylase
      and of the LIPID PHOSPHATE PHOSPHATASE gene family and ABI3-INTERACTING PROTEIN2,
      respectively. We also identified other processes, including jasmonate responses,
      cell wall modification, nitrate and nitrite reduction, mRNA stability, and blue
      light sensitivity, that were affected by after-ripening in the coleorhiza that
      may be downstream of ABA signaling. Based on these results, we propose that the
      coleorhiza plays a major role in causing dormancy by acting as a barrier to root
      emergence and that after-ripening potentiates molecular changes related to ABA
      metabolism and sensitivity that ultimately lead to degradation of the coleorhiza,
      root emergence, and germination.

PMID- 19386807
TI  - CIA2 coordinately up-regulates protein import and synthesis in leaf chloroplasts.
AB  - Plastid biogenesis and maintenance depend on the coordinated assembly of proteins
      imported from the cytosol with proteins translated within plastids. Chloroplasts
      in leaf cells have a greater need for protein import and protein synthesis than
      plastids in other organs due to the large amount of proteins required for
      photosynthesis. We previously reported that the Arabidopsis (Arabidopsis
      thaliana) transcription factor CIA2 specifically up-regulates leaf expression of
      genes encoding protein translocons Toc33 and Toc75, which are essential for
      protein import into chloroplasts. Protein import efficiency was therefore reduced
      in cia2 mutant chloroplasts. To further understand the function of CIA2, gene
      expression profiles of the wild type and a cia2 mutant were compared by
      microarray analysis. Interestingly, in addition to genes encoding protein
      translocon components, other genes down-regulated in cia2 almost exclusively
      encode chloroplast ribosomal proteins. Isolated cia2 mutant chloroplasts showed
      reduced translation efficiency and steady-state accumulation of plastid-encoded
      proteins. When CIA2 was ectopically expressed in roots, expression of both the
      protein translocon and ribosomal protein genes increased. Further analyses in
      vivo revealed that CIA2 up-regulated these genes by binding directly to their
      promoter regions. We propose that CIA2 is an important factor responsible for
      fulfilling the higher protein demands of leaf chloroplasts by coordinately
      increasing both protein import and protein translation efficiencies.

PMID- 19386808
TI  - The effects on lignin structure of overexpression of ferulate 5-hydroxylase in
      hybrid poplar.
AB  - Poplar (Populus tremula x alba) lignins with exceedingly high syringyl monomer
      levels are produced by overexpression of the ferulate 5-hydroxylase (F5H) gene
      driven by a cinnamate 4-hydroxylase (C4H) promoter. Compositional data derived
      from both standard degradative methods and NMR analyses of the entire lignin
      component (as well as isolated lignin fraction) indicated that the C4HF5H
      transgenic's lignin was comprised of as much as 97.5% syringyl units (derived
      from sinapyl alcohol), the remainder being guaiacyl units (derived from coniferyl
      alcohol); the syringyl level in the wild-type control was 68%. The resultant
      transgenic lignins are more linear and display a lower degree of polymerization.
      Although the crucial beta-ether content is similar, the distribution of other
      interunit linkages in the lignin polymer is markedly different, with higher
      resinol (beta-beta) and spirodienone (beta-1) contents, but with virtually no
      phenylcoumarans (beta-5, which can only be formed from guaiacyl units). p
      Hydroxybenzoates, acylating the gamma-positions of lignin side chains, were
      reduced by >50%, suggesting consequent impacts on related pathways. A model
      depicting the putative structure of the transgenic lignin resulting from the
      overexpression of F5H is presented. The altered structural features in the
      transgenic lignin polymer, as revealed here, support the contention that there
      are significant opportunities to improve biomass utilization by exploiting the
      malleability of plant lignification processes.

PMID- 19386809
TI  - Expression level of ABERRANT PANICLE ORGANIZATION1 determines rice inflorescence
      form through control of cell proliferation in the meristem.
AB  - Two types of branches, rachis branches (i.e. nonfloral) and spikelets (i.e.
      floral), are produced during rice (Oryza sativa) inflorescence development. We
      previously reported that the ABERRANT PANICLE ORGANIZATION1 (APO1) gene, encoding
      an F-box-containing protein orthologous to Arabidopsis (Arabidopsis thaliana)
      UNUSUAL FLORAL ORGANS, suppresses precocious conversion of rachis branch
      meristems to spikelets to ensure generation of certain number of spikelets. Here,
      we identified four dominant mutants producing an increased number of spikelets
      and found that they are gain-of-function alleles of APO1. The APO1 expression
      levels are elevated in all four mutants, suggesting that an increase of APO1
      activity caused the delay in the program shift to spikelet formation. In
      agreement with this result, ectopic overexpression of APO1 accentuated the APO1
      gain-of-function phenotypes. In the apo1-D dominant alleles, the inflorescence
      meristem starts to increase in size more vigorously than the wild type when
      switching to the reproductive development phase. This alteration in growth rate
      is opposite to what is observed with the apo1 mutants that have a smaller
      inflorescence meristem. The difference in meristem size is caused by different
      rates of cell proliferation. Collectively, these results suggest that the level
      of APO1 activity regulates the inflorescence form through control of cell
      proliferation in the meristem.

PMID- 19386810
TI  - Variations in the composition of gelling agents affect morphophysiological and
      molecular responses to deficiencies of phosphate and other nutrients.
AB  - Low inorganic phosphate (Pi) availability triggers an array of spatiotemporal
      adaptive responses in Arabidopsis (Arabidopsis thaliana). There are several
      reports on the effects of Pi deprivation on the root system that have been
      attributed to different growth conditions and/or inherent genetic variability.
      Here we show that the gelling agents, largely treated as inert components,
      significantly affect morphophysiological and molecular responses of the seedlings
      to deficiencies of Pi and other nutrients. Inductively coupled plasma-mass
      spectroscopy analysis revealed variable levels of elemental contaminants not only
      in different types of agar but also in different batches of the same agar.
      Fluctuating levels of phosphorus (P) in different agar types affected the growth
      of the seedlings under Pi-deprivation condition. Since P interacts with other
      elements such as iron, potassium, and sulfur, contaminating effects of these
      elements in different agars were also evident in the Pi-deficiency-induced
      morphological and molecular responses. P by itself acted as a contaminant when
      studying the responses of Arabidopsis to micronutrient (iron and zinc)
      deficiencies. Together, these results highlighted the likelihood of erroneous
      interpretations that could be easily drawn from nutrition studies when different
      agars have been used. As an alternative, we demonstrate the efficacy of a sterile
      and contamination-free hydroponic system for dissecting morphophysiological and
      molecular responses of Arabidopsis to different nutrient deficiencies.

PMID- 19386811
TI  - Chloroplast photooxidation-induced transcriptome reprogramming in Arabidopsis
      immutans white leaf sectors.
AB  - Arabidopsis (Arabidopsis thaliana) immutans (im) has green and white sectoring
      due to the action of a nuclear recessive gene, IMMUTANS. The green sectors
      contain normal-appearing chloroplasts, whereas the white sectors contain abnormal
      chloroplasts that lack colored carotenoids due to a defect in phytoene desaturase
      activity. Previous biochemical and molecular characterizations of the green leaf
      sectors revealed alterations suggestive of a source-sink relationship between the
      green and white sectors of im. In this study, we use an Affymetrix ATH1
      oligoarray to further explore the nature of sink metabolism in im white tissues.
      We show that lack of colored carotenoids in the im white tissues elicits a
      differential response from a large number of genes involved in various cellular
      processes and stress responses. Gene expression patterns correlate with the
      repression of photosynthesis and photosynthesis-related processes in im white
      tissues, with an induction of Suc catabolism and transport, and with
      mitochondrial electron transport and fermentation. These results suggest that
      energy is derived via aerobic and anaerobic metabolism of imported sugar in im
      white tissues for growth and development. We also show that oxidative stress
      responses are largely induced in im white tissues; however, im green sectors
      develop additional energy-dissipating mechanisms that perhaps allow for the
      formation of green sectors. Furthermore, a comparison of the transcriptomes of im
      white and norflurazon-treated white leaf tissues reveals global as well as tissue
      specific responses to photooxidation. We conclude that the differences in the
      mechanism of phytoene desaturase inhibition play an important role in
      differentiating these two white tissues.

PMID- 19386813
TI  - Palliative care in heart failure: a position statement from the palliative care
      workshop of the Heart Failure Association of the European Society of Cardiology.
AB  - Heart failure is a serious condition and equivalent to malignant disease in terms
      of symptom burden and mortality. At this moment only a comparatively small number
      of heart failure patients receive specialist palliative care. Heart failure
      patients may have generic palliative care needs, such as refractory multifaceted
      symptoms, communication and decision making issues and the requirement for family
      support. The Advanced Heart Failure Study Group of the Heart Failure Association
      of the European Society of Cardiology organized a workshop to address the issue
      of palliative care in heart failure to increase awareness of the need for
      palliative care. Additional objectives included improving the accessibility and
      quality of palliative care for heart failure patients and promoting the
      development of heart failure-orientated palliative care services across Europe.
      This document represents a synthesis of the presentations and discussion during
      the workshop and describes recommendations in the area of delivery of quality
      care to patients and families, education, treatment coordination, research and
      policy.

PMID- 19386812
TI  - Cytochrome P450 monooxygenases as reporters for circadian-regulated pathways.
AB  - Cytochrome P450 monooxygenases (P450s) play important roles in the synthesis of
      diverse secondary compounds in Arabidopsis (Arabidopsis thaliana). Comparison of
      four data sets analyzing seedlings harvested over a 2-d period of constant
      conditions after growth with varying photoperiods and thermocycles recorded a
      total of 98 P450 loci as circadian regulated for at least one of the four
      conditions. Here, we further describe the circadian-regulated pathways using, as
      reporters, individual P450 loci that are likely to be rate limiting in secondary
      metabolic pathways. Reverse transcription-polymerase chain reaction gel blot
      analyses have confirmed circadian regulation of P450s in phenylpropanoid,
      carotenoid, oxylipin, glucosinolate, and brassinosteroid biosyntheses and have
      shown that both P450 and non-P450 genes in the many branches of the
      phenylpropanoid pathway have similar circadian patterns of expression. In silico
      analyses of the subsets of coregulated promoters have identified overrepresented
      promoter elements in various biosynthetic pathway genes, including MYB and MYB4
      elements that are significantly more abundant in promoters for the core and
      lignin sections of phenylpropanoid metabolism. Interactions with these elements
      important for circadian regulation do not involve the MYB transcription factor
      PAP1, as previously proposed, since the expression patterns of circadian
      regulated P450s are the same in pap1-D mutant seedlings as in wild-type
      seedlings. Further analysis of circadian-regulated promoters in other biochemical
      pathways provides us with the opportunity to identify novel promoter motifs that
      might be important in P450 circadian regulation.

PMID- 19386814
TI  - Remote ischaemic pre-conditioning does not attenuate ischaemic left ventricular
      dysfunction in humans.
AB  - AIMS: Remote ischaemic pre-conditioning (RIPC) reduces distant tissue ischaemia
      reperfusion injury. We tested the hypothesis that RIPC would protect the left
      ventricle (LV) from ischaemic dysfunction and stunning. METHODS AND RESULTS:
      Forty-two patients with single vessel coronary disease and normal LV function
      were prospectively recruited. Twenty patients had repeated conductance catheter
      assessment of LV function during serial coronary occlusions with/without RIPC and
      a further 22 patients underwent serial dobutamine stress echocardiography and
      tissue Doppler analysis with/without RIPC. Remote ischaemic pre-conditioning was
      induced by three 5 min inflations of a blood pressure cuff around the upper arm.
      RIPC did not diminish the degree of ischaemic LV dysfunction during coronary
      balloon occlusion (Tau, ms: 59.2 (2.8) vs. 62.8 (2.8), P = 0.15) and there was
      evidence of cumulative LV dysfunction despite RIPC [ejection fraction (EF), %:
      54.3 (5.8) vs. 44.9 (3.7), P = 0.03]. Remote ischaemic pre-conditioning did not
      improve contractile recovery during reperfusion (EF, %: 51.7 (3.6) vs. 51.5
      (5.7), P = 0.88 and Tau, ms: 55.6 (2.8) vs. 56.0 (2.0), P = 0.85). A neutral
      effect of RIPC on LV function was confirmed by tissue Doppler analysis of
      ischaemic segments at peak dobutamine (V(s), cm s(-1) control: 8.2 (0.4) vs. RIPC
      8.1 (0.4), P = 0.43) and in recovery. CONCLUSION: RIPC does not attenuate
      ischaemic LV dysfunction in humans.

PMID- 19386815
TI  - Obituary to Philip Poole-Wilson 1943-2009.

PMID- 19386816
TI  - Differential success rates in racial groups: results of a clinical trial of
      smoking cessation among female prisoners.
AB  - INTRODUCTION: This study replicated prior observations of racial differences in
      smoking cessation in which Black smokers have demonstrated lower smoking
      cessation rates than White smokers. METHODS: The study used data from a smoking
      cessation intervention and compared White and Black female prisoners (N = 233) on
      a 10-week intervention of group psychotherapy and nicotine replacement (patch).
      Generalized estimating equations were used to model smoking cessation across the
      12-month follow-up. RESULTS: Compared with an untreated control group, both Black
      and White smokers benefited from the cessation treatment. However, after
      controlling for potential confounds, White smokers had significantly higher
      overall smoking cessation rates across time compared with Black smokers (e.g.,
      30% vs. 24% abstinent at 6 weeks; 13% vs. 10% abstinent at 12 months). Smoking
      mentholated cigarettes was not associated with these differences in quit rates.
      DISCUSSION: Understanding differential treatment responses can lead to the
      development of more tailored and efficacious smoking cessation interventions that
      may reduce the morbidity and mortality associated with smoking in prison
      populations.

PMID- 19386817
TI  - Measuring the oral health of nursing home elders.
AB  - The primary purposes of this descriptive and prospective pilot study was to test
      the feasibility of a nursing and dental hygiene team to measure specific oral
      health indices in a sample of older adults residing in nursing homes (NHs). The
      secondary purpose was to determine the relationship between plaque and dentate
      status. Oral health indicators, functional status scores, and behavioral scores
      were collected and analyzed from 38 female NH residents from two geographically,
      organizationally, and economically diverse NHs. Persons with dentures had
      significantly lower plaque scores than those with natural dentition. Rural NH
      residents and African American NH residents had fewer filled teeth, indicating a
      potential lack of access to dental care. Oral health indicators were collected
      safely and efficiently from NH residents using a nursing and dental hygiene
      collaborative approach. Nursing and dental hygiene collaborations hold promise
      for improving the oral health in institutionalized elders.

PMID- 19386818
TI  - Anti-cyclic citrullinated peptide and anti-keratin antibodies in patients with
      idiopathic inflammatory myopathy.
AB  - OBJECTIVE: To investigate the prevalence of anti-cyclic citrullinated peptide
      (anti-CCP) and anti-keratin antibodies (AKAs) in a cohort of patients with
      idiopathic inflammatory myopathy. METHODS: In a cross-sectional study, we
      determined the presence of anti-CCP and AKAs by ELISA and IIF, respectively, in a
      cohort of 90 consecutive patients with idiopathic inflammatory myopathy.
      Associations between anti-CCP and clinical manifestations or other autoantibodies
      were determined with the chi-square and Mann-Whitney U-tests. Radiographs of
      hands were retrospectively evaluated. Serum autoantibody profile was determined
      in all patients. RESULTS: Twelve patients were positive to anti-CCP (13.3%); in
      eight cases values were moderate-high. AKAs were not detected in any patient.
      Comparison between patients positive and negative to anti-CCP did not show
      clinical or biological differences. Arthritis joint erosions or positive status
      to anti-synthetase antibodies were not more frequent in patients with anti-CCP
      antibodies. Prevalence of RF was the only variable significantly associated with
      the presence of these antibodies (P = 0.043). CONCLUSIONS: High titres of anti
      CCP can occasionally be found in patients with inflammatory myopathy. Therefore,
      a possible diagnosis of RA should be considered with caution in these patients.

PMID- 19386819
TI  - Early diagnosis of temporomandibular joint involvement in juvenile idiopathic
      arthritis: a pilot study comparing clinical examination and ultrasound to
      magnetic resonance imaging.
AB  - OBJECTIVES: To study the validity of both rheumatological and orthodontic
      examinations and ultrasound (US) as screening methods for early diagnosis of TMJ
      arthritis against the gold standard MRI. METHODS: Thirty consecutive juvenile
      idiopathic arthritis (JIA) patients were included in this pilot study.
      Rheumatological and orthodontic examinations as well as US were performed within
      1 month of the MRI in a blinded fashion. Joint effusion and/or increased contrast
      enhancement of synovium or bone were considered signs of active arthritis on MRI.
      RESULTS: A total of 19/30 (63%) patients and 33/60 (55%) joints had signs of TMJ
      involvement on MRI. This was associated with condylar deformity in 9/19 (47%)
      patients and 15/33 (45%) joints. Rheumatological, orthodontic and US examinations
      correctly diagnosed 11 (58%), 9 (47%) and 6 (33%) patients, respectively, with
      active TMJ arthritis, but misdiagnosed 8 (42%), 10 (53%) and 12 (67%) patients,
      respectively, as having no signs of inflammation. The best predictor for active
      arthritis on MRI was a reduced maximum mouth opening. CONCLUSION: None of the
      methods tested was able to reliably predict the presence or absence of MRI-proven
      inflammation in the TMJ in our cohort of JIA patients. US was the least useful of
      all methods tested to exclude active TMJ arthritis.

PMID- 19386820
TI  - Misconceptions about high-fructose corn syrup: is it uniquely responsible for
      obesity, reactive dicarbonyl compounds, and advanced glycation endproducts?
AB  - Misconceptions about high-fructose corn syrup (HFCS) abound in the scientific
      literature, the advice of health professionals to their patients, media
      reporting, product advertising, and the irrational behavior of consumers.
      Foremost among these is the misconception that HFCS has a unique and substantive
      responsibility for the current obesity crisis. Inaccurate information from
      ostensibly reliable sources and selective presentation of research data gathered
      under extreme experimental conditions, representing neither the human diet nor
      HFCS, have misled the uninformed and created an atmosphere of distrust and
      avoidance for what, by all rights, should be considered a safe and innocuous
      sweetener. In the first part of this article, common misconceptions about the
      composition, functionality, metabolism, and use of HFCS and its purported link to
      obesity are identified and corrected. In the second part, an emerging
      misconception, that HFCS in carbonated soft drinks contributes materially to
      physiological levels of reactive dicarbonyl compounds and advanced glycation
      endproducts, is addressed in detail, and evidence is presented that HFCS does not
      pose a unique dietary risk in healthy individuals or diabetics.

PMID- 19386821
TI  - Fructose ingestion: dose-dependent responses in health research.
AB  - Many hypotheses of disease risk and prevention depend on inferences about the
      metabolic effects of fructose; however, there is inadequate attention to dose
      dependency. Fructose is proving to have bidirectional effects. At moderate or
      high doses, an effect on any one marker may be absent or even the opposite of
      that observed at very high or excessive doses; examples include fasting plasma
      triglyceride, insulin sensitivity, and the putative marker uric acid. Among
      markers, changes can be beneficial for some (e.g., glycated hemoglobin at
      moderate to high fructose intake) but adverse for others (e.g., plasma
      triglycerides at very high or excessive fructose intake). Evidence on body weight
      indicates no effect of moderate to high fructose intakes, but information is
      scarce for high or excessive intakes. The overall balance of such beneficial and
      adverse effects of fructose is difficult to assess but has important implications
      for the strength and direction of hypotheses about public health, the relevance
      of some animal studies, and the interpretation of both interventional and
      epidemiological studies. By focusing on the adverse effects of very high and
      excessive doses, we risk not noticing the potential benefits of moderate to
      higher doses, which might moderate the advent and progress of type-2 diabetes,
      cardiovascular disease, and might even contribute to longevity. A salutary rather
      than hyperbolic examination of the evidence base needs to be undertaken.

PMID- 19386822
TI  - Dietary sweeteners containing fructose: overview of a workshop on the state of
      the science.
AB  - The occurrence and impact of fructose in the American food supply has garnered
      much recent attention in the popular press as well as the scientific community.
      This paper provides an overview of a workshop cosponsored by the International
      Life Sciences Institute North America and the USDA, Agricultural Research
      Service, titled "State of the Science on Dietary Sweeteners Containing Fructose."
      Papers in the workshop addressed the chemical composition and properties of
      dietary sweeteners that contain fructose, the sources and amount of fructose in
      the American diet, and the metabolism of fructose in the human body. Further, the
      authors of each paper assessed the strength of the existing data linking dietary
      fructose intake and risk for overweight, metabolic syndrome, type 2 diabetes
      mellitus, cardiovascular disease, and other disorders. The assessment considered
      factors in study design, including the amount fed, the food form, the length of
      the study, the characteristics of the subjects, the specific methodology, and
      other potential confounders including diet. In addition to papers assessing the
      basic science of fructose, some papers also addressed consumer concern about
      sugars and fructose in the diet, the way fructose and other sugars are presented
      in the media, and the resulting confusion of consumers about fructose and other
      sugars in the diet. The purpose of the papers in the aggregate was to clarify
      what data exist about fructose and what the gaps are in the data and to help both
      scientists and consumers understand issues surrounding fructose in the food
      supply.

PMID- 19386823
TI  - Meningioma and mobile phone use.

PMID- 19386824
TI  - Reader's response: meningioma and mobile phone use--a collaborative case-control
      study in five North European countries.

PMID- 19386825
TI  - Breast cancer survival in Canada and the USA: meta-analytic evidence of a
      Canadian advantage in low-income areas.
AB  - BACKGROUND: This study tested the hypothesis that relatively poor Canadian women
      with breast cancer have a survival advantage over their counterparts in the USA.
      METHODS: Seventy-eight independent retrospective cohort (incidence between 1984
      and 2000, followed until 2006) outcomes were synthesized. Fixed effects meta
      regression models compared women with breast cancer in low-income areas of Canada
      and the USA. RESULTS: Low-income Canadian women were advantaged on survival [rate
      ratio (RR) = 1.14; 95% confidence interval (CI) 1.13-1.15] and their advantage
      was even larger among women <65 years of age who are not yet eligible for
      Medicare coverage in the USA (RR = 1.21, 95% CI 1.18-1.24). Canadian advantages
      were also larger for node positive breast cancer, which may present with greater
      clinical and managerial discretion (RR = 1.40, 95% CI 1.30-1.50), and smaller
      when Hawaii, the state providing the most Canadian-like access, was the US
      comparator (RR = 1.12, 95% CI 1.01-1.20). CONCLUSIONS: More inclusive health care
      insurance coverage in Canada vs the USA, particularly among each country's
      relatively poor people, seems the most plausible explanation for such Canadian
      advantages. Provision of health care for all Americans would likely prevent
      countless early deaths, particularly among the relatively poor.

PMID- 19386826
TI  - The impact of anticipatory grief on caregiver burden in dementia caregivers.
AB  - PURPOSE: Interest in anticipatory grief (AG) has typically focused on terminal
      diseases such as cancer. However, the issues involved in AG are unique in the
      context of dementia due to the progressive deterioration of both cognitive and
      physical abilities. The current study investigated the nature of AG in a sample
      of dementia caregivers and examined the relationship between AG and caregiver
      burden. DESIGN AND METHODS: A total of 80 informal caregivers of individuals with
      dementia completed interviews and questionnaires assessing their experience of
      grief, physical and mental health, aspects of the caregiving situation, and the
      level of patient impairment. Hierarchical linear regression models were used to
      examine whether AG is significantly associated with caregiver burden. RESULTS: AG
      was shown to be significantly and independently associated with caregiver burden
      in this sample, beyond the effects of known predictors such as background
      characteristics, behavior problems in the care recipient, and depressive
      symptoms. IMPLICATIONS: The current results suggest that grief may be an
      important yet understudied aspect of the caregiving experience. It is likely that
      consideration of grief in future conceptualizations of caregiver burden can lead
      to better support for caregivers and more accurate predictions of outcomes.

PMID- 19386827
TI  - Optimism, pessimism, mutuality, and gender: predicting 10-year role strain in
      Parkinson's disease spouses.
AB  - PURPOSE: There is wide variability in how spouses providing care respond to their
      care situations. Few studies focus on the roles of both intra- and interpersonal
      factors in long-term spousal care, particularly in the context of Parkinson's
      disease (PD). The current study uses longitudinal data over a 10-year period to
      examine the roles of optimism, pessimism, mutuality, and spouse gender in
      predicting role strain in PD spouses. DESIGN AND METHODS: A longitudinal design
      was used to study 255 spouses of persons with PD over a 10-year period, with data
      points at baseline (Year 0), Year 2, and Year 10. A series of multilevel models
      were used to examine four role strain variables -- global strain, strain from
      worry, strain from feelings of being manipulated, and strain from increased
      tension. RESULTS: Female spouse gender predicted both higher Year 10 role strain
      and faster increases in role strain over the 10-year period. In addition, high
      mutuality and optimism and low pessimism at baseline played important protective
      roles against increased role strain at Year 10. IMPLICATIONS: This study focused
      on early-stage spousal care in a primarily physical disability context. Findings
      suggest that gender differences place wives at greater risk for negative
      outcomes, even in the absence of dementia. Additionally, clinicians have
      opportunities to target interventions early in the care trajectory based on intra
      and interpersonal risk factors.

PMID- 19386828
TI  - Understanding the experience of stroke: a mixed-method research agenda.
AB  - The use of both quantitative and qualitative strategies to examine a single
      research question has been a subject of considerable controversy and still
      remains a largely uncommon practice in the sociology of health and illness. Yet,
      when seeking to understand the meaning of a chronic disabling condition in later
      life from a social psychological perspective, a mixed-method approach is likely
      to provide the most comprehensive picture. This article provides an overview of
      the usefulness and appropriateness of a mixed-method approach to understanding
      the stroke experience. I comment on the current state of research on the
      experience of stroke, including epistemological and ontological orientations.
      Using real data examples, I address paradigmatic assumptions, methods of
      integration, as well as challenges and pitfalls in integrating methods. I
      conclude by considering future directions in this field of research.

PMID- 19386829
TI  - Perceived income adequacy among older adults in 12 countries: findings from the
      survey of health, ageing, and retirement in Europe.
AB  - PURPOSE: To validate a survey research measure of subjective income, as measured
      by perceived income adequacy, in an international context. DESIGN AND METHODS:
      The study population comprised persons aged 50 years and older in 12 countries
      from the Survey of Health, Ageing and Retirement in Europe (n = 28,939).
      Perceived difficulty in making ends meet was regressed on sociodemographic
      variables, economic indicators, health status measures, and expectations
      regarding one's financial future. Country differences were also controlled.
      RESULTS: The findings confirm a multidimensional explanation of perceived income
      adequacy but also point to the primacy of objective economic indicators in
      predicting household financial distress. Respondents aged 80 years and older
      report less financial difficulty. Poor health status and pessimistic financial
      expectations also predict greater household financial distress but to a lesser
      degree. IMPLICATIONS: Self-rated economic status is a robust indicator of
      financial capacity in older age and can be used by practitioners to gain
      meaningful information. However, practitioners should keep in mind that the
      oldest-old may underestimate financial difficulties.

PMID- 19386831
TI  - Genetic relationships deduced from emm and multilocus sequence typing of invasive
      Streptococcus dysgalactiae subsp. equisimilis and S. canis recovered from
      isolates collected in the United States.
AB  - Beta-hemolytic group C and G streptococci cause a considerable invasive disease
      burden and sometimes cause disease outbreaks. Little is known about the critical
      epidemiologic parameter of genetic relatedness between isolates. We determined
      the emm types of 334 Streptococcus dysgalactiae subsp. equisimilis isolates, and
      attempted emm typing of 5 Streptococcus canis isolates from a recent population
      based surveillance for invasive isolates. Thirty-four emm types were observed,
      including one from S. canis. We formulated multilocus sequence typing (MLST)
      primers with six of the seven loci corresponding to the Streptococcus pyogenes
      MLST scheme. We performed MLST with 65 of the 334 surveillance isolates (61 S.
      dysgalactiae subsp. equisimilis isolates, 4 S. canis isolates) to represent each
      emm type identified, including 2 to 3 isolates for each of the 25 redundantly
      represented emm types. Forty-one MLST sequence types (STs) were observed.
      Isolates within 16 redundantly represented S. dysgalactiae subsp. equisimilis emm
      types shared identical or nearly identical STs, demonstrating concordance between
      the emm type and genetic relatedness. However, seven STs were each represented by
      two to four different emm types, and 7 of the 10 S. dysgalactiae subsp.
      equisimilis eBURST groups represented up to six different emm types. Thus, S.
      dysgalactiae subsp. equisimilis isolates were similar to S. pyogenes isolates, in
      that strains of the same emm type were often highly related, but they differed
      from S. pyogenes, in that S. dysgalactiae subsp. equisimilis strains with
      identical or closely similar STs often exhibited multiple unrelated emm types.
      The phylogenetic relationships between S. dysgalactiae subsp. equisimilis and S.
      pyogenes alleles revealed a history of interspecies recombination, with either
      species often serving as genetic donors. The four S. canis isolates shared highly
      homologous alleles but were unrelated clones without evidence of past
      recombination with S. dysgalactiae subsp. equisimilis or S. pyogenes.

PMID- 19386830
TI  - Pediatric Helicobacter pylori isolates display distinct gene coding capacities
      and virulence gene marker profiles.
AB  - Helicobacter pylori strains display remarkable genetic diversity, and the
      presence of strains bearing the toxigenic vacA s1 allele, a complete cag
      pathogenicity island (PAI), cagA alleles containing multiple EPIYA
      phosphorylation sites, and expressing the BabA adhesin correlates with
      development of gastroduodenal disease in adults. To better understand the genetic
      variability present among pediatric strains and its relationship to disease, we
      characterized H. pylori strains infecting 47 pediatric North American patients.
      Prevalence of mixed infection was assessed by random amplified polymorphic DNA
      analysis of multiple H. pylori clones from each patient. Microarray-based
      comparative genomic hybridization was used to examine the genomic content of the
      pediatric strains. The cagA and vacA alleles were further characterized by allele
      specific PCR. A range of EPIYA motif configurations were observed for the cagA
      gene, which was present in strains from 22 patients (47%), but only 19 (41%)
      patients contained a complete cag PAI. Thirty patients (64%) were infected with a
      strain having the vacA s1 allele, and 28 patients (60%) had the babA gene. The
      presence of a functional cag PAI was correlated with ulcer disease (P = 0.0095).
      In spite of declining rates of H. pylori infection in North America, at least 11%
      of patients had mixed infection. Pediatric strains differ in their spectrum of
      strain-variable genes and percentage of absent genes in comparison to adult
      strains. Most children were infected with H. pylori strains lacking the cag PAI,
      but the presence of a complete cag PAI, in contrast to other virulence markers,
      was associated with more severe gastroduodenal disease.

PMID- 19386832
TI  - Endocarditis due to Neisseria bacilliformis in a patient with a bicuspid aortic
      valve.
AB  - We report a case of endocarditis due to the rod-shaped Neisseria species
      Neisseria bacilliformis. The phenotypic characterization of this recently
      characterized bacteria is difficult, and the identification requires the
      sequencing of the 16S rRNA gene. The resolution of the disease was complete after
      appropriate antibiotic therapy, and surgery was not required.

PMID- 19386833
TI  - Spontaneous bacterial pericarditis with tamponade due to Ureaplasma spp.
AB  - Infectious pericardial effusion with tamponade is an uncommon but life
      threatening disease. We report an unusual case of spontaneous Ureaplasma
      pericardial effusion with tamponade associated with pneumonia, pleural effusion,
      and urinary tract infection. All published cases of clinically invasive
      Ureaplasma infections in the adult population are also reviewed.

PMID- 19386834
TI  - Complete genome sequence and phylogenetic relatedness of hepatitis B virus
      isolates in Papua, Indonesia.
AB  - Each hepatitis B virus (HBV) genotype and subgenotype is associated with a
      particular geographic distribution, ethnicity, and anthropological history. Our
      previous study showed the novel HBV subgenotypes C6 (HBV/C6) and D6 (HBV/D6),
      based on the S gene sequences of isolates in Papua, Indonesia. The present study
      investigated the complete genome sequence of 22 strains from Papua and subjected
      them to molecular evolutionary analysis. A phylogenetic analysis revealed that 9
      out of 22 strains were classified as HBV/C6, 3 strains as HBV/D6, and 9 strains
      as HBV/B3. A particular strain positioned between HBV/B3 and HBV/B5 remained
      unclassifiable into any known subgenotypes. This strain showed high homology with
      HBV/C5 from the Philippines in the core region and was thought to have undergone
      genetic recombination with HBV/C5. Further studies are needed to determine
      whether this strain belongs to a new subgenotype of HBV/B. Based on the amino
      acid alignment, HBV/C6 has subgenotype specific variations (G18V and V47M) in the
      S region. HBV/C6 strains were more closely related in terms of evolutionary
      distance to strains from the east Asia and Pacific regions than those found in
      southeast Asia. HBV/D6 strains were most closely related to strains from the
      Western countries (HBV/D3) rather than those from Asia and Papua New Guinea. In
      conclusion, we have confirmed by complete sequence analysis that two novel HBV
      subgenotypes, HBV/C6 and HBV/D6, are prevalent in Papua, Indonesia.

PMID- 19386835
TI  - Pulmonary disease due to Mycobacterium arosiense, an easily misidentified
      pathogenic novel mycobacterium.
AB  - Mycobacterium arosiense is a newly described species. After noticing it was
      misidentified as Mycobacterium intracellulare by the commercial identification
      system GenoType CM (Hein, Nehren, Germany), we detected 4 such strains among 33
      that were previously misidentified as M. intracellulare. Three more strains were
      found among unidentified mycobacteria not tested previously with GenoType. The
      first case of pulmonary disease due to M. arosiense is reported here, and the
      novel species, of which so far only one strain had been investigated, is further
      characterized.

PMID- 19386836
TI  - Detection of plasmid-mediated quinolone resistance genes in clinical isolates of
      Enterobacter spp. in Spain.
AB  - We have studied by PCR and DNA sequencing the presence of the qnrA, qnrB, qnrS,
      aac(6')-Ib-cr, qepA, intI1, and ISCR1 genes in 200 clinical isolates of
      Enterobacter cloacae (n = 153) and E. aerogenes (n = 47) consecutively collected
      between January 2004 and October 2005 in two hospitals located in Santander
      (northern Spain) and Seville (southern Spain). Mutations in the quinolone
      resistance-determining region of gyrA and parC also were investigated in
      organisms containing plasmid-mediated quinolone resistance genes. The isolates
      had different resistant phenotypes, including AmpC hyperproduction, extended
      spectrum beta-lactamase production, resistance or decreased susceptibility to
      quinolones, and/or resistance to aminoglycosides. Among the 116 E. cloacae
      isolates from Santander, qnrS1, qnrB5, qnrB2, and aac(6')-Ib-cr were detected in
      22 (19%), 1 (0.9%), 1 (0.9%), and 3 (2.6%) isolates, respectively. Twenty-one,
      17, and 2 qnrS1-positive isolates also contained bla(LAP-1), intI1, and ISCR1,
      respectively. A qnrB7-like gene was detected in one E. aerogenes isolate from
      Santander. No plasmid-mediated quinolone resistance gene was detected in the
      isolates from Seville. The qnrS1-containing isolates corresponded to four pulsed
      field gel electrophoresis patterns and showed various levels of resistance to
      quinolones. Six isolates were susceptible to nalidixic acid and presented reduced
      susceptibility to ciprofloxacin. The qnrS1 gene was contained in a conjugative
      plasmid of ca. 110 kb, and when the plasmid was transferred to recipient strains
      that did not have a specific mechanism of quinolone resistance, the ciprofloxacin
      MICs ranged from 0.047 to 0.125 microg/ml.

PMID- 19386837
TI  - Enrichment broth improved detection of extended-spectrum-beta-lactamase-producing
      bacteria in throat and rectal surveillance cultures of samples from patients in
      intensive care units.
AB  - We evaluated the use of a trypticase soy broth (TSB) for improving detection of
      extended-spectrum-beta-lactamase-producing (ESBL(+)) bacteria. Preenrichment of
      throat and rectal swabs in TSB prior to inoculation on solid medium doubled the
      number of ESBL(+) bacteria detected in samples obtained from patients in our
      intensive care unit.

PMID- 19386838
TI  - Performance of three nucleic acid amplification tests for detection of Chlamydia
      trachomatis and Neisseria gonorrhoeae by use of self-collected vaginal swabs
      obtained via an Internet-based screening program.
AB  - Use of self-obtained vaginal specimens processed by nucleic acid amplification
      tests (NAATs) has significantly increased the utilization of nontraditional
      locations for Chlamydia trachomatis and Neisseria gonorrhoeae screening programs.
      One important emerging source of such venues includes home-based self-sampling
      kits available via the Internet. The objective of our study was to evaluate the
      performance of three commercially available NAATs (Becton-Dickinson ProbeTec SDA,
      Gen-Probe Aptima Combo2 TMA, and Roche Amplicor PCR) for detection of C.
      trachomatis and N. gonorrhoeae in vaginal samples obtained via an Internet-based
      screening program. From July 2004 to August 2005, 500 self-collected vaginal
      swabs were tested for C. trachomatis and N. gonorrhoeae by using all three NAATs.
      Another 500 samples were collected between August 2005 and November 2007 and
      tested by ProbeTec and Combo2; PCR testing was discontinued due to low
      specificity for N. gonorrhoeae. All tests were conducted according to the
      manufacturers' procedures; the "gold standard" for an infected C. trachomatis or
      N. gonorrhoeae patient was defined as > or = 2 positive NAAT results. Of the
      first 500 swabs submitted, 46 were C. trachomatis infected (9.2%) and 5 were N.
      gonorrhoeae infected (1.0%), and 3 of these were coinfected (0.6%). All C.
      trachomatis and N. gonorrhoeae Combo2-positive/ProbeTec-negative samples were
      confirmed as true positives by an alternative NAAT. For C. trachomatis, ProbeTec,
      Combo2, and PCR had sensitivities of 82.6%, 100%, and 100%, with specificities of
      100%, 100%, and 99.3%, respectively. For N. gonorrhoeae, ProbeTec, Combo2, and
      PCR had sensitivities of 80%, 100%, and 100%, with specificities of 100%, 100%,
      and 98.8%, respectively. Of the total 1,000 swabs submitted, 92 were C.
      trachomatis infected (9.2%) and 15 were N. gonorrhoeae infected (1.5%), and 7 of
      these were coinfected (0.7%). There were no ProbeTec-positive/Combo2-negative
      samples. For C. trachomatis, ProbeTec and Combo2 had sensitivities of 81.5% and
      100%, with specificities of 100% and 100%, respectively. For N. gonorrhoeae,
      ProbeTec and Combo2 had sensitivities of 80% and 100%, with specificities of 100%
      and 100%, respectively. Overall, ProbeTec had 17 C. trachomatis false-negative
      results (1.7%) and 3 N. gonorrhoeae false-negative results (0.3%), while Combo2
      had none. Our results were consistent with the sensitivities and specificities
      stated by the manufacturers. NAATs perform well for detection of chlamydia and
      gonorrhea with self-obtained vaginal swabs shipped in a dry state to a
      laboratory. For 1,000 self-collected vaginal swabs tested by NAATs, the
      sensitivities for C. trachomatis and N. gonorrhoeae for Combo2 were 100% and
      100%, while they were 81.5% and 80%, respectively, for ProbeTec. For 500 PCR
      samples, the C. trachomatis sensitivity was 100% and the N. gonorrhoeae
      sensitivity was 100%, with specificities of 99.3% and 98.8%, respectively.

PMID- 19386840
TI  - First Spanish case of nocardiosis caused by Nocardia takedensis.
AB  - Nocardia takedensis is a recently described species isolated from soil. The first
      clinical isolate in Japan has recently been reported. This report describes the
      first clinical isolate of N. takedensis in Spain from a respiratory specimen.

PMID- 19386839
TI  - Rapid variable-number tandem-repeat genotyping for Mycobacterium leprae clinical
      specimens.
AB  - Mycobacterium leprae is the noncultivable pathogen of leprosy. Since the genome
      sequence of an isolate of M. leprae has become available, multiple-locus variable
      number tandem-repeat (VNTR) analysis (MLVA) has been explored as a tool for
      strain typing and identification of chains of transmission of leprosy. In order
      to discover VNTRs and develop methods transferable to clinical samples, MLVA was
      applied to a global collection of M. leprae isolates derived from leprosy
      patients and propagated in armadillo hosts. PCR amplification, agarose gel
      electrophoresis, and sequencing methods were applied to DNA extracts from these
      infected armadillo tissues (n = 21). We identified polymorphisms in 15 out of 25
      short-tandem-repeat (STR) loci previously selected by in silico analyses of the
      M. leprae genome. We then developed multiplex PCR for amplification of these 15
      loci in four separate PCRs suitable for fluorescent fragment length analysis and
      demonstrated STR profiles highly concordant with those from the sequencing
      methods. Subsequently, we extended this method to DNA extracts from human
      clinical specimens, such as skin biopsy specimens (n = 30). With these
      techniques, mapping of multiple loci and differentiation of genotypes have been
      possible using total DNA extracts from limited amounts of clinical samples at a
      reduced cost and with less time. These practical methods are therefore available
      and applicable to answer focused epidemiological questions and to allow
      monitoring of the transmission of M. leprae in different countries where leprosy
      is endemic.

PMID- 19386841
TI  - Cutaneous infection caused by Macrophomina phaseolina in a child with acute
      myeloid leukemia.
AB  - We report a case of Macrophomina phaseolina skin infection in an
      immunocompromised child with acute myeloid leukemia, which was treated
      successfully with posaconazole without recurrence after a hematopoietic stem cell
      transplant. The fungus was identified by DNA sequencing using both the internal
      transcribed spacer and D1/D2 region of the 28S ribosomal DNA gene.

PMID- 19386842
TI  - No correlation between giant cell arteritis and Chlamydia pneumoniae infection:
      investigation of 189 patients by standard and improved PCR methods.
AB  - A total of 189 temporal artery biopsy samples from giant cell arteritis (GCA)
      patients were investigated using sensitive PCR targeting Chlamydia pneumoniae.
      Chlamydial DNA was detected in 17 samples, 11 of which were positive for
      chlamydial antigens. Our data did not reveal strong evidence that C. pneumoniae
      plays an important role in the pathogenesis of GCA.

PMID- 19386843
TI  - Detection of Streptococcus pneumoniae strain cocolonization in the nasopharynx.
AB  - Colonization with more than one distinct strain of the same species, also termed
      cocolonization, is a prerequisite for horizontal gene transfer between
      pneumococcal strains that may lead to change of the capsular serotype. Capsule
      switch has become an important issue since the introduction of conjugated
      pneumococcal polysaccharide vaccines. There is, however, a lack of techniques to
      detect multiple colonization by S. pneumoniae strains directly in nasopharyngeal
      samples. Two hundred eighty-seven nasopharyngeal swabs collected during the
      prevaccine era within a nationwide surveillance program were analyzed by a novel
      technique for the detection of cocolonization, based on PCR amplification of a
      noncoding region adjacent to the pneumolysin gene (plyNCR) and restriction
      fragment length polymorphism (RFLP) analysis. The numbers of strains and their
      relative abundance in cocolonized samples were determined by terminal RFLP. The
      pneumococcal carriage rate found by PCR was 51.6%, compared to 40.0% found by
      culture. Cocolonization was present in 9.5% (10/105) of samples, most (9/10) of
      which contained two strains in a ratio of between 1:1 and 17:1. Five of the 10
      cocolonized samples showed combinations of vaccine types only (n = 2) or
      combinations of nonvaccine types only (n = 3). Carriers of multiple pneumococcal
      strains had received recent antibiotic treatment more often than those colonized
      with a single strain (33% versus 9%, P = 0.025). This new technique allows for
      the rapid and economical study of pneumococcal cocolonization in nasopharyngeal
      swabs. It will be valuable for the surveillance of S. pneumoniae epidemiology
      under vaccine selection pressure.

PMID- 19386844
TI  - Rapid group-, serotype-, and vaccine strain-specific identification of poliovirus
      isolates by real-time reverse transcription-PCR using degenerate primers and
      probes containing deoxyinosine residues.
AB  - We have adapted our previously described poliovirus diagnostic reverse
      transcription-PCR (RT-PCR) assays to a real-time RT-PCR (rRT-PCR) format. Our
      highly specific assays and rRT-PCR reagents are designed for use in the WHO
      Global Polio Laboratory Network for rapid and large-scale identification of
      poliovirus field isolates.

PMID- 19386845
TI  - Feasibility of the GenoType MTBDRsl assay for fluoroquinolone, amikacin
      capreomycin, and ethambutol resistance testing of Mycobacterium tuberculosis
      strains and clinical specimens.
AB  - The new GenoType Mycobacterium tuberculosis drug resistance second line (MTBDRsl)
      assay (Hain Lifescience, Nehren, Germany) was tested on 106 clinical isolates and
      directly on 64 sputum specimens for the ability to detect resistance to
      fluoroquinolones, injectable drugs (amikacin or capreomycin), and ethambutol in
      Mycobacterium tuberculosis strains. A total of 63 strains harboring
      fluoroquinolone, amikacin/capreomycin, or ethambutol resistance and 43 fully
      susceptible strains were comparatively analyzed with the new MTBDRsl assay, by
      DNA sequencing, and by conventional drug susceptibility testing in liquid and
      solid media. No discrepancies were obtained in comparison with the DNA sequencing
      results. Fluoroquinolone resistance was detected in 29 (90.6%) of 32,
      amikacin/capreomycin resistance was detected in 39/39 (84.8%/86.7%) of 46/45, and
      ethambutol resistance was detected in 36 (69.2%) of 52 resistant strains. A total
      of 64 sputum specimens (42 smear positive, 12 scanty, and 10 smear negative) were
      tested with the new MTBDRsl assay, and the results were compared with those of
      conventional drug susceptibility testing. Fluoroquinolone resistance was detected
      in 8 (88.9%) of 9, amikacin/capreomycin resistance was detected in 6/7
      (75.0%/87.5%) of 8, and ethambutol resistance was detected in 10 (38.5%) of 26
      resistant strains. No mutation was detected in susceptible strains. The new
      GenoType MTBDRsl assay represents a reliable tool for the detection of
      fluoroquinolone and amikacin/capreomycin resistance and to a lesser extent also
      ethambutol resistance. In combination with a molecular test for detection of
      rifampin and isoniazid resistance, the potential for the detection of extensively
      resistant tuberculosis within 1 to 2 days can be postulated.

PMID- 19386846
TI  - Evaluation of the new Vitek 2 ANC card for identification of medically relevant
      anaerobic bacteria.
AB  - Of 261 anaerobic clinical isolates tested with the new Vitek 2 ANC card, 257
      (98.5%) were correctly identified at the genus level. Among the 251 strains for
      which identification at the species level is possible with regard to the ANC
      database, 217 (86.5%) were correctly identified at the species level. Two strains
      (0.8%) were not identified, and eight were misidentified (3.1%). Of the 21
      strains (8.1%) with low-level discrimination results, 14 were correctly
      identified at the species level by using the recommended additional tests. This
      system is a satisfactory new automated tool for the rapid identification of most
      anaerobic bacteria isolated in clinical laboratories.

PMID- 19386847
TI  - Fine-needle aspiration, an efficient sampling technique for bacteriological
      diagnosis of nonulcerative Buruli ulcer.
AB  - Invasive punch or incisional skin biopsy specimens are currently employed for the
      bacteriological confirmation of the clinical diagnosis of Buruli ulcer (BU), a
      cutaneous infectious disease caused by Mycobacterium ulcerans. The efficacy of
      fine-needle aspirates (FNA) using fine-gauge needles (23G by 25 mm) for the
      laboratory confirmation of BU was compared with that of skin tissue fragments
      obtained in parallel by excision or punch biopsy. In three BU treatment centers
      in Benin, both types of diagnostic material were obtained from 33 clinically
      suspected cases of BU and subjected to the same laboratory analyses: i.e., direct
      smear examination, IS2404 PCR, and in vitro culture. Twenty-three patients,
      demonstrating 17 ulcerative and 6 nonulcerative lesions, were positive by at
      least two tests and were therefore confirmed to have active BU. A total of 68
      aspirates and 68 parallel tissue specimens were available from these confirmed
      patients. When comparing the sensitivities of the three confirmation tests
      between FNA and tissue specimens, the latter yielded more positive results, but
      only for PCR was this significant. When only nonulcerative BU lesions were
      considered, however, the sensitivities of the confirmation tests using FNA and
      tissue specimens were not significantly different. Our results show that the
      minimally invasive FNA technique offers enough sensitivity to be used for the
      diagnosis of BU in nonulcerative lesions.

PMID- 19386848
TI  - Genetic variability of group A human respiratory syncytial virus strains
      circulating in Germany from 1998 to 2007.
AB  - The variability between respiratory syncytial virus (RSV) strains is one of the
      features of RSV infections that might contribute to the ability of the virus to
      infect people repeatedly and cause yearly outbreaks. To study the molecular
      epidemiology of RSV, more than 1,400 RSV isolates from human nasopharyngeal
      aspirates or nasal or throat swabs from patients with respiratory illness were
      identified and differentiated by TaqMan reverse transcription-PCR into groups A
      and B. RSV group A was dominant in seven out of nine epidemic seasons.
      Phylogenetic analysis revealed that RSV group A genotypes GA2 and GA5 circulated
      from 1998 to 2007. Genotype GA7 was present in only two seasons (1999 to 2000 and
      2002 to 2003). Comparison of the synonymous mutation/nonsynonymous mutation
      ratios showed greater evidence for selection pressure for genotype GA2 (1.18)
      than for GA5 (4.34). Partial protein sequences were predicted to encode G
      proteins of 298 amino acids in length and in a few cases of G proteins of 297
      amino acids in length. Amino acid analysis also revealed genotype-specific amino
      acid substitutions: two substitutions for genotype GA2, seven for GA5, and three
      for GA7. Two to four putative, genotype-specific N-linked glycosylation sites
      were determined. Predicted O-glycosylation sites included 22 to 34 residues. This
      study provides for the first time data on the circulation pattern of RSV group A
      genotypes and their molecular characterization in Germany during nine consecutive
      epidemic seasons.

PMID- 19386849
TI  - Cost-effective frozen master mix modification of a commercial methicillin
      resistant Staphylococcus aureus PCR assay.
AB  - The expense inherent to molecular diagnostics may be an overriding concern for a
      variety of clinical laboratories in the development of PCR-based methicillin
      resistant Staphylococcus aureus (MRSA) active surveillance programs. BD GeneOhm
      MRSA assay master mix was reconstituted, aliquoted into SmartCycler tubes in 25
      microl volumes, and frozen at -70 degrees C. One hundred percent of archival
      nasal swab lysates yielded the expected PCR results when incubated in master mix
      frozen for 1, 2, 3, and 4 weeks. A 98.8% concordance of the final result was
      observed upon prospective PCR analysis of 320 clinical lysates utilizing freshly
      reconstituted master mix and 2-week-frozen master mix. Initial unresolved rates
      generated by frozen master mix and freshly reconstituted master mix differed by
      1.6% (P = 0.16). Of 50 MRSA-positive lysates, the titers of 32 (64%) were
      determined to the same value upon initial tandem frozen master mix and freshly
      reconstituted master mix utilization; the titers of an additional 14 were
      determined to the same value upon repeat testing. Frozen master mix maintains
      potency for at least 4 weeks, facilitating detection of MRSA from nasal swab
      lysates, and may decrease the amount of unused reagent up to an average of 33%.

PMID- 19386850
TI  - Sensitive screening tests for suspected class A carbapenemase production in
      species of Enterobacteriaceae.
AB  - The detection of class A serine-carbapenemases among species of
      Enterobacteriaceae remains a challenging issue. Methods of identification for
      routine use in clinical microbiology laboratories have not been standardized to
      date. We developed a novel screening methodology suitable for countries with high
      basal levels of carbapenem resistance due to non-carbapenemase-mediated
      mechanisms and standardized several simple confirmatory methods that allow the
      recognition of bacteria producing class A carbapenemases, including KPC, Sme,
      IMI, NMC-A, and GES, by using boronic acid (BA) derivatives. A total of 28
      genetically unrelated Enterobacteriaceae strains producing several class A
      carbapenemases were tested. Thirty-eight genetically unrelated negative controls
      were included. The isolates were tested against imipenem (IPM), meropenem (MEM),
      and ertapenem (ETP) by MIC and disk diffusion assays in order to select
      appropriate tools to screen for suspected carbapenemase production. It was
      possible to differentiate class A carbapenemase-producing bacteria from non
      carbapenemase-producing bacteria by using solely the routine IPM susceptibility
      tests. The modified Hodge test was evaluated and found to be highly sensitive,
      although false-positive results were documented. Novel BA-based methods (a double
      disk synergy test and combined-disk and MIC tests) using IPM, MEM, and ETP, in
      combination with 3-aminophenylboronic acid as an inhibitor, were designed as
      confirmatory tools. On the basis of the performance of these methods, a sensitive
      flow chart for suspicion and confirmation of class A carbapenemase production in
      species of Enterobacteriaceae was designed. By using this methodology, isolates
      producing KPC, GES, Sme, IMI, and NMC-A carbapenemases were successfully
      distinguished from those producing other classes of beta-lactamases (extended
      spectrum beta-lactamases, AmpCs, and metallo-beta-lactamases, etc). These methods
      will rapidly provide useful information needed for targeting antimicrobial
      therapy and appropriate infection control.

PMID- 19386851
TI  - Activity of contemporary antifungal agents, including the novel echinocandin
      anidulafungin, tested against Candida spp., Cryptococcus spp., and Aspergillus
      spp.: report from the SENTRY Antimicrobial Surveillance Program (2006 to 2007).
AB  - Results from the SENTRY international fungal surveillance program for 2006 to
      2007 are presented. A total of 1,448 Candida sp., 49 Aspergillus fumigatus, and
      33 Cryptococcus neoformans isolates were obtained from infected sterile-site
      sources in patients on five continents. Reference susceptibility was determined
      for anidulafungin, caspofungin, 5-flucytosine, fluconazole, itraconazole,
      posaconazole, voriconazole, and amphotericin B by CLSI methods.

PMID- 19386852
TI  - Are putative periodontal pathogens reliable diagnostic markers?
AB  - Periodontitis is one of the most common chronic inflammatory diseases. A number
      of putative bacterial pathogens have been associated with the disease and are
      used as diagnostic markers. In the present study, we compared the prevalence of
      oral bacterial species in the subgingival biofilm of generalized aggressive
      periodontitis (GAP) (n = 44) and chronic periodontitis (CP) (n = 46) patients
      with that of a periodontitis-resistant control group (PR) (n = 21). The control
      group consisted of subjects at least 65 years of age with only minimal or no
      periodontitis and no history of periodontal treatment. A total of 555 samples
      from 111 subjects were included in this study. The samples were analyzed by PCR
      of 16S rRNA gene fragments and subsequent dot blot hybridization using
      oligonucleotide probes specific for Aggregatibacter (Actinobacillus)
      actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia,
      Tannerella forsythia, a Treponema denticola-like phylogroup (Treponema phylogroup
      II), Treponema lecithinolyticum, Campylobacter rectus, Fusobacterium spp., and
      Fusobacterium nucleatum, as well as Capnocytophaga ochracea. Our data confirm a
      high prevalence of the putative periodontal pathogens P. gingivalis, P.
      intermedia, and T. forsythia in the periodontitis groups. However, these species
      were also frequently detected in the PR group. For most of the species tested,
      the prevalence was more associated with increased probing depth than with the
      subject group. T. lecithinolyticum was the only periodontopathogenic species
      showing significant differences both between GAP and CP patients and between GAP
      patients and PR subjects. C. ochracea was associated with the PR subjects,
      regardless of the probing depth. These results indicate that T. lecithinolyticum
      may be a diagnostic marker for GAP and C. ochracea for periodontal health. They
      also suggest that current presumptions of the association of specific bacteria
      with periodontal health and disease require further evaluation.

PMID- 19386853
TI  - Outbreak of nontuberculous mycobacterial subcutaneous infections related to
      multiple mesotherapy injections.
AB  - We describe an outbreak of severe subcutaneous infections due to nontuberculous
      mycobacteria following mesotherapy. Epidemiological studies and molecular
      comparisons of Mycobacterium chelonae strains from different patients and the
      environment suggested that contamination may be associated with inappropriate
      cleaning of the multiple-injection device with tap water.

PMID- 19386854
TI  - High diversity of Mycobacterium tuberculosis genotypes in South Africa and
      preponderance of mixed infections among ST53 isolates.
AB  - The reemergence of tuberculosis (TB) has become a major health problem worldwide,
      especially in Asia and Africa. Failure to combat this disease due to nonadherence
      or inappropriate drug regimens has selected for the emergence of multiple-drug
      resistant (MDR) TB. The development of new molecular genotyping techniques has
      revealed the presence of mixed Mycobacterium tuberculosis infections, which may
      accelerate the emergence of drug-resistant strains. There are some studies
      describing the local distribution of circulating strains in South Africa, but to
      date, reports describing the frequency and distribution of M. tuberculosis
      genotypes, and specifically MDR genotypes, across the different provinces are
      limited. Thus, 252 isolates (of which 109 were MDR) from eight of the nine
      provinces of South Africa were analyzed by spoligotyping. Spoligotyping showed 10
      different lineages, and ST53 (11.1%) and ST1 (10.3%) were the most frequent
      genotypes. Of the 75 different spoligopatterns observed, 20 (7.9%) were
      previously unreported. Analysis of the mycobacterial interspersed repetitive
      units of variable-number tandem repeats of the ST53 and ST1 isolates revealed
      that approximately 54% of the ST53 isolates were of mixed M. tuberculosis
      subpopulations. Drug resistance (defined as resistance to at least isoniazid
      and/or rifampin) could only be linked to a history of previous anti-TB treatment
      (adjusted odds ratio, 4.0; 95% confidence interval, 2.27 to 7.10; P = <0.0001).
      This study describes a high diversity of circulating genotypes in South Africa in
      addition to a high frequency of mixed M. tuberculosis subpopulations among the
      ST53 isolates. MDR TB in South Africa could not be attributed to the spread of
      any single lineage.

PMID- 19386855
TI  - Multilocus variable-number tandem-repeat method for typing Salmonella enterica
      serovar Newport.
AB  - In recent years, the proportion of Salmonella enterica infections represented by
      S. enterica serovar Newport has increased markedly among humans and animals.
      Multilocus variable-number tandem-repeat analysis (MLVA) has proven to be useful
      in discriminating other highly clonal Salmonella serovars. Here, we report on the
      development of a highly discriminatory MLVA for Salmonella serovar Newport.

PMID- 19386856
TI  - Spectrum of zygomycete species identified in clinically significant specimens in
      the United States.
AB  - Several members of the order Mucorales (subphylum Mucoromycotina) are important
      agents of severe human infections. The identification of these fungi by using
      standard mycologic methods is often difficult and time consuming. Frequently, the
      etiological agent in clinical cases is reported either as a Mucor sp., which is
      not the most frequent genus of zygomycetes, or only as a member of the Mucorales.
      For this reason, the actual spectrum of species of zygomycetes and their
      incidences in the clinical setting is not well known. The goals of this study
      were to compare the results of the molecular identification of an important set
      of clinical isolates, received in a mycological reference center from different
      regions of the United States, with those obtained by using the traditional
      morphological methods and to determine the spectrum of species involved. We
      tested 190 isolates morphologically identified as zygomycetes by using sequencing
      of the internal transcribed spacer (ITS) region of the ribosomal DNA. Molecular
      identification revealed that Rhizopus oryzae represented approximately half
      (44.7%) of these isolates. The remainder was identified as Rhizopus microsporus
      (22.1%), Mucor circinelloides (9.5%), Mycocladus corymbifer (formerly Absidia
      corymbifera) (5.3%), Rhizomucor pusillus (3.7%), Cunninghamella bertholletiae
      (3.2%), Mucor indicus (2.6%), Cunninghamella echinulata (1%), and Apophysomyces
      elegans (0.5%). The most common anatomic sites for clinically significant
      zygomycetes, as determined by isolates sent to the Fungus Testing Laboratory for
      identification and/or susceptibility testing and included in this study, were the
      sinuses, lungs, and various cutaneous locations, at 25.8%, 26.8%, and 28%,
      respectively. These sites represented approximately 80% of the isolates
      evaluated. A high level of correlation (92.6%) between morphological and
      molecular identifications was found.

PMID- 19386858
TI  - Aequanimitas.

PMID- 19386857
TI  - Evaluation of impact of serial hepatitis B virus DNA levels on development of
      hepatocellular carcinoma.
AB  - We aimed to investigate the impact of hepatitis B virus (HBV) DNA on the
      development of hepatocellular carcinoma (HCC). We conducted a case/control study
      based on 506 chronic HBV patients followed up since 1997. Forty-one patients
      developed HCC, and each of them was age and gender matched with two
      simultaneously recruited controls without HCC. HBV DNA was measured at the
      initial visit, at yearly intervals, and at the last visit. Patient age at the
      time of HCC development was 55 +/- 9 years. Forty-nine (40%) patients experienced
      antiviral treatment. The median time from diagnosis to the development of HCC was
      17 months, and the control patients were followed for 92 months. At the trough
      level (defined as lowest level among all studied visits), more (27 patients; 66%)
      HCC patients had HBV DNA levels of >10,000 copies/ml than the controls (17
      patients; 21%). The area under the receiver operating characteristic curve of the
      trough log HBV DNA level for HCC was 0.79 (95% confidence interval [CI], 0.69 to
      0.89). Trough log HBV DNA (odds ratio, 11.4; 95% CI, 3.6 to 37.6; P < 0.0001) and
      liver cirrhosis (odds ratio, 11.4; 95% CI, 3.6 to 36.2; P < 0.0001) levels were
      independently associated with HCC after an adjustment for age, gender, antiviral
      treatment, and HBV genotype. The difference in the trough HBV DNA level was more
      obvious among untreated patients (5.7 +/- 1.4 log copies/ml in HCC patients
      versus 3.2 +/- 1.3 log copies/ml in control patients; P < 0.0001) than among
      those who had received antiviral treatment (3.0 +/- 1.4 log copies/ml in HCC
      patients versus 2.5 +/- 0.9 log copies/ml in control patients; P = 0.38). A high
      trough HBV DNA level was associated with a higher risk of HCC. Whether antiviral
      treatment could prevent HCC was uncertain.

PMID- 19386860
TI  - Packers, pushers and stuffers--managing patients with concealed drugs in UK
      emergency departments: a clinical and medicolegal review.
AB  - Body packing, pushing and stuffing are methods by which illicit drugs may be
      carried within the human body. Patients involved in these practices may present
      UK emergency departments with complex medical, legal and ethical considerations.
      This review article examines not only the evidence behind the clinical management
      of these patients, but also the legal powers afforded to the authorities to
      authorise the use of intimate searches and diagnostic imaging for forensic
      purposes. Serious complications from concealed drug packets are now rare, and
      most asymptomatic patients may be safely discharged from hospital after
      assessment. Emergency surgery is indicated for body packers with cocaine
      poisoning and for some cases of heroin poisoning. Urgent surgery is indicated for
      obstruction, perforation, the passage of packet fragments and failure of
      conservative treatment. Guidance is given for doctors who are faced with requests
      from the authorities to perform intimate searches and diagnostic imaging for
      forensic purposes.

PMID- 19386861
TI  - In an emergency--call the clinical librarian!
AB  - This paper reviews the role of the clinical librarian in the emergency
      department.

PMID- 19386862
TI  - Intravenous thrombolysis for ischaemic stroke: short delays and high community
      based treatment rates after organisational changes in a previously inexperienced
      centre.
AB  - AIM: To evaluate hospital delays in thrombolytic treatment before and after
      organisational changes and community-based treatment rates in a previously
      inexperienced centre. METHODS: The delays before and after organisational changes
      made in 2006 were compared using a prospective treatment database. In a 6-month
      period in 2007, a community-based search was performed for all hospitalisations
      for ischaemic stroke. The number of patients admitted within the 0-3 h time
      window and the proportion treated with tissue plasminogen activator were
      analysed. RESULTS: The number of treatments increased fourfold from 2005 to 2007
      with a significant reduction in mean door-to-needle time from 60 min to 38 min (p
      = 0.002). In the community-based series, 14/137 patients (10%) hospitalised with
      ischaemic stroke and 13/32 patients (41%) admitted in the 0-3 h window were
      treated. CONCLUSIONS: An inexperienced stroke centre can rapidly implement the
      necessary logistics to deliver thrombolysis to a large proportion of patients
      with acute stroke with short hospital delays. Important factors are probably
      prenotification of a team and the initiation of thrombolytic treatment in the
      emergency room.

PMID- 19386863
TI  - Acute gastric dilatation.

PMID- 19386864
TI  - Basic cardiac life support education for non-medical hospital employees.
AB  - BACKGROUND: The International Liaison Committee on Resuscitation (ILCOR)
      recommends that strategies should be implemented that promote cardiopulmonary
      resuscitation (CPR) training in the workplace. Non-medical employees at a
      hospital were therefore trained to conduct basic life support (BLS). Subject
      background information, test results and survey findings were examined and
      factors affecting BLS skill acquisition were studied. METHODS: Of 1432 non
      medical employees at a hospital trained to conduct BLS, 880 agreed to participate
      in the survey. The training course consisted of a single session of 3 h of
      lectures, practice and testing. Skill acquisition was assessed using a 13-item
      skill checklist and a 5-point overall competency scale. The effects of age,
      gender, type of job, educational status, a previous history of CPR training and
      level of subject-perceived training difficulty were examined. RESULTS: According
      to total checklist scores, subjects achieved a mean (SD) score of 8.66 (3.57).
      22.3% performed all 13 skills. Based on 5-point overall competency ratings, 43.7%
      of subjects were rated as "competent", "very good" or "outstanding". Age (<40
      years and >or=40 years) was the only factor that significantly affected skill
      acquisition (skill acquisition by those >or=40 years of age was poorer than by
      those aged <40 years). CONCLUSION: Traditional BLS training is less effective in
      individuals aged >or=40 years.

PMID- 19386865
TI  - Syncope management in the UK and Republic of Ireland.
AB  - AIMS: To establish the current practice of emergency department (ED) management
      of syncope in the UK and Republic of Ireland. METHODS: A survey of "major" or
      "intermediate" size ED in the UK and Republic of Ireland conducted by postal and
      telephone questionnaire. RESULTS: 177 (70%) ED responded. 32 (18%) ED have
      syncope guidelines, which are based on a range of existing guidelines. 97 ED
      (55%) have an observation ward or clinical decision unit and 48 (49%) of these
      admit syncope patients to these units. 32 ED (18%) have access to a specialist
      syncope outpatient clinic. This is most likely to be run by general practitioner
      specialists (43%) or general physicians (24%). 81% of ED felt that improved
      research-based guidelines would be useful when managing syncope patients.
      CONCLUSION: The ED management of syncope patients in the UK and Republic of
      Ireland is varied. Only 18% of ED have specific guidelines for managing this
      difficult condition and only 18% have access to a specialist syncope clinic. A
      robust consensus UK syncope guideline is clearly required.

PMID- 19386866
TI  - Emergency abdominal aortic aneurysm presenting without haemodynamic shock is
      associated with misdiagnosis and delay in appropriate clinical management.
AB  - BACKGROUND: Emergency abdominal aortic aneurysm (EmAAA) represents a spectrum of
      disease from symptomatic non-ruptured aneurysms to free intraperitoneal rupture,
      with significantly worse outcomes for patients in a haemodynamically shocked
      state before surgery. A study was undertaken to see if the preoperative journey
      and outcome were different in patients who deviated from the classic acutely
      shocked presentation. METHODS: An observational database compiled from case notes
      of patients undergoing surgery for EmAAA at Sunderland Royal Hospital between
      April 2000 and October 2006 was interrogated to examine details of patient
      preoperative journey, physiological status and 30-day survival. Comparison
      between groups was performed using chi(2) analysis and the Mann-Whitney U test
      where appropriate. RESULTS: Records for 98 patients were available for review.
      Overall 30-day mortality was 49%, and was significantly higher for patients in
      shock at induction of anaesthesia than in those who were haemodynamically stable
      (59.6% vs 34.1%, p = 0.01). At presentation, 56 patients were stable and
      misdiagnosis was significantly more common in these patients than in those who
      were in shock (58.9% vs 26.2%, p = 0.002), with a significantly increased median
      time delay from presentation to diagnosis (144 min (IQR 24-366) vs 12 min (IQR 0
      42), p<0.0001). Median time from diagnosis to arrival in theatre was
      significantly longer in patients who were haemodynamically stable at presentation
      (90 min (IQR 60-150) vs 48 min (IQR 36-90), p = 0.02). Of the 56 patients who
      were haemodynamically stable at presentation, 19 underwent haemodynamic
      decompensation before surgery with a significantly increased mortality compared
      with those who remained stable (73.7% vs 37.8%, p = 0.02). Of these 19 patients,
      only 5 were correctly diagnosed at presentation. CONCLUSIONS: Diagnosis and
      treatment of EmAAA in haemodynamically stable patients is often delayed, with the
      risk of significant rupture and haemodynamic decompensation which is associated
      with poor outcome. Correct diagnosis and treatment before development of shock
      has the potential to reduce mortality.

PMID- 19386867
TI  - Relationship between intensive care complications and costs and initial 24 h
      events of trauma patients with severe haemorrhage.
AB  - BACKGROUND: The correlation between the events occurring in the initial 24 h
      following traumatic injury and the outcome of patients presenting with
      hypovolaemic shock is not clear. METHODS: 27 patients who presented to a regional
      trauma centre with severe hypovolaemic shock were prospectively monitored.
      Evidence of severe hypovolaemia and shock was noted on admission with a mean
      systolic blood pressure of 73.8 mm Hg and a mean lactate level of 6.6 mM/l. The
      patients received a mean of 21.7 litres intravenous fluids during the first 24 h
      to maintain a mean systolic blood pressure >or=110 mm Hg and urine output of
      >or=50 ml/h. Multiple metabolic and physiological parameters were obtained
      prospectively and on an almost hourly basis for the first 24 h after admission.
      Patients were followed throughout their stay in hospital to record outcome,
      complications, total hospital costs and length of stay. RESULTS: Using regression
      and multivariate analysis, adult respiratory distress syndrome was correlated
      with hypothermia and persistent lactic acidosis (R(2) = 0.65, p = 0.005).
      Coagulopathy was associated with hypothermia (R(2) = 0.43, p = 0.04). Length of
      stay and cost of hospitalisation were highly related to intensive care unit days,
      hospital-acquired infections and ventilator days (R(2) = 0.86, p = 0.03).
      CONCLUSION: The initial 24 h events of trauma patients with haemorrhagic shock
      may have a significant impact on hospital costs and on complications developing
      later during hospitalisation.

PMID- 19386868
TI  - Validation study of a transcutaneous carbon dioxide monitor in patients in the
      emergency department.
AB  - BACKGROUND: Transcutaneous carbon dioxide tension (TcPco(2)) monitors offer a non
      invasive method of continuously measuring arterial carbon dioxide tensions. The
      concordance between the TcPco(2) measurement and the value obtained from arterial
      blood gas sampling (Paco(2)) was measured in patients attending the emergency
      department. METHODS: A prospective observational cohort study was performed in 49
      adult patients who were undergoing arterial blood gas sampling as part of their
      assessment. Blood gas sampling and recording of the TcPco(2) level from the
      monitor was done simultaneously. Concordance between the two values (Paco(2) and
      TcPco(2)) was demonstrated using the method described by Bland and Altman.
      RESULTS: The mean difference was 0.02 kPa (95% CI -0.11 to 0.15). The Pearson's
      correlation coefficient was 0.94 (p<0.001) and the Bland-Altman limits of
      agreement were +/-0.9 kPa. CONCLUSIONS: In adult patients, concordance between
      carbon dioxide measurements by transcutaneous monitor and arterial blood sampling
      is good. Using the transcutaneous method, patients may be monitored non
      invasively which may reduce the need for repeated blood gas sampling.

PMID- 19386869
TI  - Comparison of bupivacaine and lidocaine with epinephrine for digital nerve
      blocks.
AB  - OBJECTIVE: This study compared the efficacy in terms of pain of injection, time
      of onset and duration of action of digital blocks of bupivacaine 0.5% alone and
      lidocaine 1% with epinephrine (1:100,000). METHODS: A randomised double-blind
      prospective study was performed in a single self-controlled group of 12 healthy
      volunteers (4 women, 8 men). Each participant was randomised to receive either
      lidocaine 1% with epinephrine (1:100,000) or bupivacaine 0.5% in either the right
      or left middle finger. Pain of injection was measured as the primary outcome
      using a 0-100 mm visual analogue scale. The time before anaesthesia to pinpricks
      was recorded and the duration of anaesthesia was reported by all volunteers.
      Statistical analysis was conducted using the non-parametric Wilcoxon signed rank
      test. RESULTS: Median visual analogue scale scores were significantly different
      between the lidocaine + epinephrine and bupivacaine groups (26.00 mm (4-52) vs
      40.50 mm (10-71), p<0.05). The median time before anaesthesia to pinpricks was
      not significantly different between the two drugs (3.45 min (3-8) vs 3.30 min (3
      8), p = 0.84). The median time needed for return of pinpricks was significantly
      different between the two drugs (321 min (228-463) vs 701 min (245-913), p<0.05).
      Follow-up was completed at 24 h. CONCLUSION: Lidocaine (1%) with epinephrine
      (1:100 000) was significantly less painful and had a shorter duration of action
      than bupivacaine (0.5%), which had a similar onset of action for digital nerve
      block. TRIAL REGISTRATION NUMBER: ISRCTN45121950.

PMID- 19386871
TI  - A simple, effective and cheap device for the safe irrigation of open traumatic
      wounds.
AB  - This study reports the use of an overturned plastic gallipot from a sterile wound
      dressing pack as a splashguard during the irrigation of traumatic wounds with a
      device consisting of a 20 ml syringe and a 21F gauge hypodermic needle. This
      simple, effective and cheap device can be constructed from items readily
      available within the emergency department or operating theatre and minimises
      exposure to biologically hazardous material during wound irrigation.

PMID- 19386870
TI  - Oculovagal reflex in paediatric orbital floor fractures mimicking head injury.
AB  - BACKGROUND: The oculovagal reflex is well described in ophthalmic surgery, but
      may be caused by any manner of pressure on the globe. Children with orbital
      blowout fractures present in a different manner from adults. The classic
      presentation in children is a white eye injury (ie, no subconjunctival
      haemorrhage) with upgaze diplopia and general malaise. METHODS: A retrospective
      audit is presented of paediatric and young adult patients referred to the Orbital
      Service at St George's Hospital who required surgical intervention. RESULTS: One
      third of children with orbital blowout fractures are admitted for head injury
      observations, while the true cause for the symptoms goes unrecognised and
      uninvestigated. CONCLUSIONS: Orbital blowout fractures in children require more
      swift intervention than in adults if muscle ischaemia and permanent impairment of
      the vision is to be avoided. The delay for head injury observation may therefore
      compromise the surgical outcome.

PMID- 19386872
TI  - A life-threatening sign, gas in the kidney is produced by bacteria: bilateral
      emphysematous pyelonephritis.

PMID- 19386873
TI  - Best evidence topic reports. Bet 1. Managing acute pulmonary oedema: high or
      standard dose glyceryl trinitrate?

PMID- 19386875
TI  - Best evidence topic reports. Bet 2. Troponin for 30-day risk stratification in
      chest pain patients with ischaemic ECG.

PMID- 19386876
TI  - Best evidence topic reports. Bet 4. Spiral computed tomography scan or
      intravenous urography in renal colic?

PMID- 19386877
TI  - Best evidence topic reports. Bet 3. Endotracheal adrenaline in intubated patients
      with asthma.

PMID- 19386878
TI  - Helicopter emergency medical system in a region lacking trauma coordination
      (experience from Tehran).
AB  - BACKGROUND: The helicopter emergency medical service (HEMS) has been working in
      Iran since 2000. The present study is the first prospective research to determine
      the epidemiological characteristics of injured patients transported by helicopter
      in Tehran. METHODS: All injured patients brought to three hospitals from the
      injury scene by HEMS were reviewed in a 4-month period. RESULTS: The mean
      transport time was 54 minutes. The most common mechanism of trauma was road
      traffic accidents (96.2%). The mean injury severity score was 8.6 (SD 8.6) and
      9.6% of patients were sent to the intensive care unit; 10.2% of patients died.
      CONCLUSION: This study shows that overtriage in HEMS (transportation of patients
      without severe injuries) and the long transportation time is mainly a result of
      not having a trauma system. The study has shown HEMS to be an effective and
      feasible option in countries with heavy traffic and no trauma system.

PMID- 19386879
TI  - Views regarding the provision of prehospital critical care in the UK.
AB  - AIMS: There is a lack of consensus regarding the role for critical care in the
      prehospital environment in the UK. It was hypothesised that this related to
      differences in views and understanding among opinion leaders within influential
      prehospital care organisations. METHODS: A 38-item survey was developed by an
      established paramedic-physician prehospital critical care service. The survey was
      distributed to individuals in senior positions within seven organisations that
      have a major influence on UK prehospital services. Analysis comprised a
      description of the distribution of results, assessment of the level of agreement
      with each statement by professional background and current involvement in
      prehospital critical care and evaluation of the overall consistency of responses.
      Free-text comments were invited to illustrate the reasoning behind each response.
      RESULTS: There were 32 respondents. The estimated response rate was 40%. The
      consistency of the questionnaire responses was very high. Overall, all
      individuals agreed with most of the statements. Paramedic respondents were more
      likely to disagree with statements that suggested that critical care involved
      interventions that exceed the current capability of the NHS ambulance service
      (p<0.05). Free-text comments revealed wide differences of opinion. CONCLUSION:
      Although there appears to be broad agreement among opinion leaders regarding the
      concepts underpinning existing prehospital critical care services, areas of
      contention are highlighted that may help explain the current lack of consensus.
      Cooperative efforts to assess the current demand and clinical evidence would
      assist in the creation of a joint consensus and allow effective future planning
      for the provision of prehospital critical care throughout the UK.

PMID- 19386880
TI  - Evaluation of attitudes and perceptions of key clinical stakeholders regarding
      out-of-hospital diagnosis and treatment of ST elevation myocardial infarction
      patients using a region-wide survey.
AB  - INTRODUCTION: In ST elevation myocardial infarction (STEMI), prehospital
      management (PHM) may improve clinical outcomes through a reduction in reperfusion
      delay. The purpose of this study was to evaluate perceptions among healthcare
      stakeholder groups relating to the barriers and facilitators of implementing a
      PHM programme. METHODS: A 25-question cross-sectional survey, using a four-point
      Likert scale assessing barriers and facilitators of PHM, was distributed to
      paramedics, cardiologists, emergency physicians and emergency nurses within the
      Edmonton region, where prehospital STEMI treatment is established. The proportion
      of responses on each question was compared and differences between groups were
      determined using chi(2) and Fisher's exact tests. RESULTS: 57% (355/619) of
      subjects responded: 69% paramedics, 50% cardiologists, 54% emergency physicians
      and 45% emergency nurses. A majority believed PHM reduced treatment delays in
      both rural (96-100%) and urban (86-96%) areas, while decreasing patient mortality
      (paramedics 97%, cardiologists 74%, emergency physicians 85%, emergency nurses
      88%). Regarding the capability of paramedics to deliver PHM, paramedics 25%,
      cardiologists 33%, emergency physicians 67%, and emergency nurses 47% stated that
      urban paramedics are better equipped and trained than rural paramedics. Although
      81% of paramedics supported the possibility of PHM delivery without physician
      overview, 0% of cardiologists, 98% of emergency physicians and 95% emergency
      nurses agreed. A majority (71-88%) favoured mandatory signed informed consent.
      CONCLUSIONS: While stakeholders agreed on the benefits of PHM, perceptual
      differences existed on paramedics' ability to deliver PHM without physician
      overview. Addressing real and perceived barriers through communication and
      educational programmes may enhance PHM within this healthcare region and
      facilitate the implementation of PHM programmes.

PMID- 19386881
TI  - Can DVD simulations provide an effective alternative for paramedic clinical
      placement education?
AB  - OBJECTIVE: This study aimed to evaluate the usability of DVD simulations, the
      impact on student learning satisfaction and the potential for using DVD
      simulations to reduce the clinical placement burden on the current healthcare
      system. The clinical DVD simulations were underpinned by interprofessional
      educational principles that supported clinical placements for paramedic students.
      METHOD: Eleven DVD simulations were developed by academic staff members from
      Monash University with input and feedback from a team of healthcare
      professionals. Students (N = 97) from the Bachelor of Emergency Health at Monash
      University viewed the DVD simulations. Students' perceptions, attitudes and
      thoughts about the clinical relevance of the simulations were assessed by
      completing a standardised self-report 7-point Likert scale questionnaire (7
      indicating the highest satisfaction score). Qualitative data assessing if and how
      the DVD simulations had influenced paramedic students' clinical placement
      learning experiences were also collected via two focus groups (n = 6). RESULTS:
      Overall, paramedic students positively perceived the DVD simulations with
      relation to learning satisfaction (mean (SD) 5.14 (1.14), 95% CI 4.91 to 5.37)
      and information processing quality (mean (SD) 5.50 (0.83), 95% CI 5.33 to 5.67).
      The simulations maintained students' attention and concentration (mean (SD) 4.35
      (0.95), 95% CI 4.15 to 4.54) and provided clinical authenticity and relevance to
      practice (mean (SD) 4.27 (0.65), 95% CI 4.14 to 4.40). A number of themes emerged
      from the focus group data including the impact on employment, greater
      appreciation of healthcare teamwork and notion of interdisciplinary teamwork, the
      fact that DVD simulations have the capacity to replace some clinical placement
      rotations and should be integrated into standard curriculum, and that varying
      amounts of learning wastage occur during clinical placements. CONCLUSIONS: DVD
      simulations with an interprofessional education focus were developed. Paramedic
      students reported the simulations as being educationally, professionally and
      clinically relevant. The students also identified some aspects of current
      clinical placements that may be replaced by using DVD simulations. The cost
      benefit of using interprofessional DVD simulations to supplement and replace
      certain clinical placement rotations should be investigated further.

PMID- 19386882
TI  - Severe rhabdomyolysis after recreational training.
AB  - A 26-year-old woman presented at the emergency department with 4 days' bilateral
      lower limb pain and swollen upper legs. Serum creatine kinase was elevated to 33
      736 mmol. A diagnosis of rhabdomyolysis was made and she was treated using a
      rhabdomyolysis algorithm.

PMID- 19386883
TI  - Diagnostically challenging tumour in a great vessel: leiomyosarcoma of inferior
      vena cava.

PMID- 19386884
TI  - A headache not to be sneezed at.
AB  - A 32-year-old male patient presented to the emergency department (ED) complaining
      of a headache and vertigo precipitated by sneezing. He had a recent history of
      neck trauma. Examination revealed horizontal nystagmus and a gait that veered to
      the left, exacerbated by heel to toe walking. A diagnosis of vertebral artery
      dissection (VAD) was suspected. A bleed was ruled out in the ED by computerised
      tomography, after which the patient was loaded with aspirin. The diagnosis was
      confirmed by magnetic resonance imaging and magnetic resonance angiography.
      Although optimal treatment for VAD is unknown, the Cervical Artery Dissection in
      Stroke Study (CADISS) is an ongoing randomised multicentre prospective study
      comparing antiplatelet therapy with anticoagulation for patients with both
      carotid artery dissection and VAD. Headache is a very common presentation to the
      ED and a full neurological examination is essential if rarer causes are not to be
      missed.

PMID- 19386885
TI  - An unusual case of neonatal ileus.

PMID- 19386886
TI  - Seat belt injury causing delayed sigmoid colon fistula.
AB  - Seat belt use can decrease the mortality rate associated with road traffic
      accidents (RTA). However, there is an increased risk of bowel perforations among
      seat belt wearers, possibly as a result of improper use. A case is reported of a
      female passenger who presented with an abdominal wall fistula 2 weeks after a
      RTA.

PMID- 19386887
TI  - Ascending aortic injury: computed tomography is not enough.
AB  - A case of an ascending aortic injury caused by a fall from height is presented.
      The patient had a suspicion of this injury identified on chest x ray and computed
      tomography (CT) scan. Subsequent aortography was necessary to clarify further the
      type and location of injury. This case highlights the potential difference in
      management between ascending aortic injuries and more common descending aortic
      injuries (in which diagnosis and choice of treatment can be based on CT alone).
      After CT has identified a possible ascending aortic injury, aortography is needed
      because CT images of this region are less diagnostic and clear.

PMID- 19386889
TI  - How deep is your sedation?

PMID- 19386890
TI  - Ethics and analgesia.

PMID- 19386891
TI  - Harms of targets.

PMID- 19386893
TI  - The T-cell-receptor signaling network.

PMID- 19386894
TI  - CTCF and its protein partners: divide and rule?
AB  - CTCF is a ubiquitous transcription factor that is involved in numerous, seemingly
      unrelated functions. These functions include, but are not limited to, positive or
      negative regulation of transcription, enhancer-blocking activities at
      developmentally regulated gene clusters and at imprinted loci, and X-chromosome
      inactivation. Here, we review recent data acquired with state-of-the-art
      technologies that illuminate possible mechanisms behind the diversity of CTCF
      functions. CTCF interacts with numerous protein partners, including cohesin,
      nucleophosmin, PARP1, Yy1 and RNA polymerase II. We propose that CTCF interacts
      with one or two different partners according to the biological context, applying
      the Roman principle of governance, 'divide and rule' (divide et impera).

PMID- 19386896
TI  - Aberrant function and structure of retinal ribbon synapses in the absence of
      complexin 3 and complexin 4.
AB  - Complexins regulate the speed and Ca(2+) sensitivity of SNARE-mediated synaptic
      vesicle fusion at conventional synapses. Two of the vertebrate complexins, Cplx3
      and Cplx4, are specifically localized to retinal ribbon synapses. To test whether
      Cplx3 and Cplx4 contribute to the highly efficient transmitter release at ribbon
      synapses, we studied retina function and structure in Cplx3 and Cplx4 single- and
      double-knockout mice. Electroretinographic recordings from single and double
      mutants revealed a cooperative perturbing effect of Cplx3 and Cplx4 deletion on
      the b-wave amplitude, whereas most other detected effects in both plexiform
      synaptic layers were additive. Light and electron microscopic analyses uncovered
      a disorganized outer plexiform layer in the retinae of mice lacking Cplx3 and
      Cplx4, with a significant proportion of photoreceptor terminals containing
      spherical free-floating ribbons. These structural and functional aberrations were
      accompanied by behavioural deficits indicative of a vision deficit. Our results
      show that Cplx3 and Cplx4 are essential regulators of transmitter release at
      retinal ribbon synapses. Their loss leads to aberrant adjustment and fine-tuning
      of transmitter release at the photoreceptor ribbon synapse, alterations in
      transmission at bipolar cell terminals, changes in the temporal structure of
      synaptic processing in the inner plexiform layer of the retina and perturbed
      vision.

PMID- 19386895
TI  - Filaggrin in the frontline: role in skin barrier function and disease.
AB  - Recently, loss-of-function mutations in FLG, the human gene encoding profilaggrin
      and filaggrin, have been identified as the cause of the common skin condition
      ichthyosis vulgaris (which is characterised by dry, scaly skin). These mutations,
      which are carried by up to 10% of people, also represent a strong genetic
      predisposing factor for atopic eczema, asthma and allergies. Profilaggrin is the
      major component of the keratohyalin granules within epidermal granular cells.
      During epidermal terminal differentiation, the approximately 400 kDa profilaggrin
      polyprotein is dephosphorylated and rapidly cleaved by serine proteases to form
      monomeric filaggrin (37 kDa), which binds to and condenses the keratin
      cytoskeleton and thereby contributes to the cell compaction process that is
      required for squame biogenesis. Within the squames, filaggrin is citrullinated,
      which promotes its unfolding and further degradation into hygroscopic amino
      acids, which constitute one element of natural moisturising factor. Loss of
      profilaggrin or filaggrin leads to a poorly formed stratum corneum (ichthyosis),
      which is also prone to water loss (xerosis). Recent human genetic studies
      strongly suggest that perturbation of skin barrier function as a result of
      reduction or complete loss of filaggrin expression leads to enhanced percutaneous
      transfer of allergens. Filaggrin is therefore in the frontline of defence, and
      protects the body from the entry of foreign environmental substances that can
      otherwise trigger aberrant immune responses.

PMID- 19386897
TI  - Characterization of Snail nuclear import pathways as representatives of C2H2 zinc
      finger transcription factors.
AB  - Snail proteins are C(2)H(2) class zinc finger transcription factors involved in
      different processes during embryonic development, as well as in several adult
      pathologies including cancer and organ fibrosis. The expression of Snail
      transcription factors is tightly regulated at the transcriptional level and their
      activity is modulated by their subcellular localization. Given the importance of
      this gene family in physiology and pathology, it is essential to understand the
      mechanisms by which Snail proteins are imported into or exported out of the
      nucleus. Here we show that several importins mediate the nuclear import of the
      human Snail proteins and we identify a unique nuclear localization signal (NLS),
      recognized by all the importins, that has been conserved during the evolution of
      the Snail family. This NLS is characterized by the presence of basic residues at
      defined positions in at least three consecutive zinc fingers. Interestingly, the
      consensus residues for importin-binding are also involved in DNA binding,
      suggesting that importins could prevent non-specific binding of these
      transcription factors to cytoplasmic polyanions. Importantly, the identified
      basic residues are also conserved in other families of C(2)H(2) transcription
      factors whose nuclear localization requires the zinc finger region.

PMID- 19386898
TI  - Glycosylation-related gene expression profiling in the brain and spleen of
      scrapie-affected mouse.
AB  - A central event in the formation of infectious prions is the conformational
      change of a host-encoded glycoprotein, PrP(C), into a pathogenic isoform,
      PrP(Sc). The molecular requirements for efficient PrP conversion remain unknown.
      Altered glycosylation has been linked to various pathologies and the N-glycans
      harbored by two prion protein isoforms are different. In order to search for
      glycosylation-related genes that could mark prion infection, we used a
      glycosylation-dedicated microarray that allowed the simultaneous analysis of the
      expression of 165 glycosylation-related genes encoding proteins of the
      glycosyltransferase, glycosidase, lectin, and sulfotransferase families to
      compare the gene expression profiles of normal and scrapie-infected mouse brain
      and spleen. Eight genes were found upregulated in "scrapie brain" at the final
      state of the disease. In the spleen, five genes presented a modified expression.
      Three genes were also upregulated in the spleen of infected mice, and two (Pigq
      and St3gal5) downregulated. All changes were confirmed by qPCR and biochemical
      analyses applied to Pigq and St3gal5 proteins.

PMID- 19386899
TI  - Converging evidence for the Nogo-66 receptor gene in schizophrenia.

PMID- 19386900
TI  - The primate retina contains distinct types of Y-like ganglion cells.

PMID- 19386901
TI  - Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap
      junctions.
AB  - MECP2, an X-linked gene encoding the epigenetic factor methyl-CpG-binding protein
      2, is mutated in Rett syndrome (RTT) and aberrantly expressed in autism. Most
      children affected by RTT are heterozygous Mecp2-/+ females whose brain function
      is impaired postnatally due to MeCP2 deficiency. While prior functional
      investigations of MeCP2 have focused exclusively on neurons and have concluded
      the absence of MeCP2 in astrocytes, here we report that astrocytes express MeCP2,
      and MeCP2 deficiency in astrocytes causes significant abnormalities in BDNF
      regulation, cytokine production, and neuronal dendritic induction, effects that
      may contribute to abnormal neurodevelopment. In addition, we show that the MeCP2
      deficiency state can progressively spread at least in part via gap junction
      communications between mosaic Mecp2-/+ astrocytes in a novel non-cell-autonomous
      mechanism. This mechanism may lead to the pronounced loss of MeCP2 observed
      selectively in astrocytes in mouse Mecp2-/+ brain, which is coincident with
      phenotypic regression characteristic of RTT. Our results suggest that astrocytes
      are viable therapeutic targets for RTT and perhaps regressive forms of autism.

PMID- 19386903
TI  - Brain injury does not alter the intrinsic differentiation potential of adult
      neuroblasts.
AB  - Neuroblasts produced by the neural stem cells of the adult subventricular zone
      (SVZ) migrate into damaged brain areas after stroke or other brain injuries, and
      previous data have suggested that they generate regionally appropriate new
      neurons. To classify the types of neurons produced subsequent to ischemic injury,
      we combined BrdU or virus labeling with multiple neuronal markers to characterize
      new cells at different times after the induction of stroke. We show that SVZ
      neuroblasts give rise almost exclusively to calretinin-expressing cells in the
      damaged striatum, resulting in the accumulation of these cells during long term
      recovery after stroke. The vast majority of SVZ neuroblasts as well as newly born
      young and mature neurons in the damaged striatum constitutively express the
      transcription factor Sp8, but do not express transcription factors characteristic
      of medium-sized spiny neurons, the primary striatal projection neurons lost after
      stroke. Our results suggest that adult neuroblasts do not alter their intrinsic
      differentiation potential after brain injury.

PMID- 19386902
TI  - Complex intrinsic membrane properties and dopamine shape spiking activity in a
      motor axon.
AB  - We studied the peripheral motor axons of the two pyloric dilator (PD) neurons of
      the stomatogastric ganglion in the lobster, Homarus americanus. Intracellular
      recordings from the motor nerve showed both fast and slow voltage- and activity
      dependent dynamics. During rhythmic bursts, the PD axons displayed changes in
      spike amplitude and duration. Pharmacological experiments and the voltage
      dependence of these phenomena suggest that inactivation of sodium and A-type
      potassium channels are responsible. In addition, the "resting" membrane potential
      was dependent on ongoing spike or burst activity, with more hyperpolarized values
      when activity was strong. Nerve stimulations, pharmacological block and current
      clamp experiments suggest that this is due to a functional antagonism between a
      slow after-hyperpolarization (sAHP) and inward rectification through
      hyperpolarization-activated current (IH). Dopamine application resulted in modest
      depolarization and "ectopic" peripheral spike initiation in the absence of
      centrally generated activity. This effect was blocked by CsCl and ZD7288,
      consistent with a role of IH. High frequency nerve stimulation inhibited
      peripheral spike initiation for several seconds, presumably due to the sAHP. Both
      during normal bursting activity and antidromic nerve stimulation, the conduction
      delay over the length of the peripheral nerve changed in a complex manner. This
      suggests that axonal membrane dynamics can have a substantial effect on the
      temporal fidelity of spike patterns propagated from a spike initiation site to a
      synaptic target, and that neuromodulators can influence the extent to which spike
      patterns are modified.

PMID- 19386904
TI  - Organization of intralaminar and translaminar neuronal connectivity in the
      superficial spinal dorsal horn.
AB  - The spinal dorsal horn exhibits a high degree of intrinsic connectivity that is
      critical to its role in the processing of nociceptive information. To examine the
      spatial organization of this intrinsic connectivity, we used laser-scanning
      photostimulation in parasagittal and transverse slices of lumbar spinal cord to
      stimulate presynaptic neurons by glutamate uncaging, and mapped the location of
      sites that provide excitatory and inhibitory synaptic input to neurons of the
      superficial laminae. Excitatory interneuronal connectivity within lamina II
      exhibited a pronounced sagittal orientation, in keeping with the somatotopic
      organization present in the pattern of primary afferent projections. Excitatory
      inputs to all classes of lamina II neurons arose from a wider rostrocaudal area
      than inhibitory inputs, whereas both excitatory and inhibitory input zones were
      restricted mediolaterally. Lamina I-II neurons exhibited cell type-specific
      patterns in the laminar distribution of their excitatory inputs that were related
      to their dorsoventral dendritic expanse. All cell types received excitatory input
      predominantly from positions ventral to that of their soma, but in lamina I
      neurons and lamina II vertical cells this ventral displacement of the excitatory
      input zone was greater than in the other cell types, resulting in a more
      pronounced translaminar input pattern. A previously unknown excitatory input to
      the superficial dorsal horn from lamina III-IV was identified in a subset of the
      vertical cell population. These results reveal a specific three-dimensional
      organization in the local patterns of excitatory and inhibitory connectivity that
      has implications for the processing of information related to both somatotopy and
      sensory modality.

PMID- 19386905
TI  - Role of protein kinase C in the induction and maintenance of serotonin-dependent
      enhancement of the glutamate response in isolated siphon motor neurons of Aplysia
      californica.
AB  - Serotonin (5-HT) mediates learning-related facilitation of sensorimotor synapses
      in Aplysia californica. Under some circumstances 5-HT-dependent facilitation
      requires the activity of protein kinase C (PKC). One critical site of PKC's
      contribution to 5-HT-dependent synaptic facilitation is the presynaptic sensory
      neuron. Here, we provide evidence that postsynaptic PKC also contributes to
      synaptic facilitation. We investigated the contribution of PKC to enhancement of
      the glutamate-evoked potential (Glu-EP) in isolated siphon motor neurons in cell
      culture. A 10 min application of either 5-HT or phorbol ester, which activates
      PKC, produced persistent (> 50 min) enhancement of the Glu-EP. Chelerythrine and
      bisindolylmaleimide-1 (Bis), two inhibitors of PKC, both blocked the induction of
      5-HT-dependent enhancement. An inhibitor of calpain, a calcium-dependent
      protease, also blocked 5-HT's effect. Interestingly, whereas chelerythrine
      blocked maintenance of the enhancement, Bis did not. Because Bis has greater
      selectivity for conventional and novel isoforms of PKC than for atypical
      isoforms, this result implicates an atypical isoform in the maintenance of 5-HT's
      effect. Although induction of enhancement of the Glu-EP requires protein
      synthesis (Villareal et al., 2007), we found that maintenance of the enhancement
      does not. Maintenance of 5-HT-dependent enhancement appears to be mediated by a
      PKM-type fragment generated by calpain-dependent proteolysis of atypical PKC.
      Together, our results suggest that 5-HT treatment triggers two phases of PKC
      activity within the motor neuron, an early phase that may involve conventional,
      novel or atypical isoforms of PKC, and a later phase that selectively involves an
      atypical isoform.

PMID- 19386906
TI  - The occurrence of aging-dependent reticulon 3 immunoreactive dystrophic neurites
      decreases cognitive function.
AB  - Reticulon 3 (RTN3) has been shown to mark a distinct and abundant population of
      dystrophic neurites named RTN3 immunoreactive dystrophic neurites (RIDNs) in
      patients' brains of Alzheimer disease (AD). Transgenic mice expressing RTN3 (Tg
      RTN3) also spontaneously develop RIDNs. To determine whether RIDNs formed in Tg
      RTN3 mice would ever naturally occur in the nontransgenic mouse brain, we
      targeted our examination to elderly mouse brains on the basis that AD is an age
      dependent neurodegenerative disease where the decline in cognitive function
      becomes progressively increased during the course of the disease. Here, we
      demonstrate that the distribution of RIDNs is abundant, rather than sporadic, in
      elderly but not young mouse brains. RIDNs in the elderly brain have two distinct
      populations: abundantly dispersed RIDNs that can only be marked by RTN3, and less
      abundantly clustered RIDNs that can be marked by multiple proteins including
      RTN3, ubiquitin, and phosphorylated neurofilament. The abundance of RIDNs in Tg
      RTN3 mice at the age of 3 months resembles that of 24-month-old wild type mice,
      suggesting that this animal model mimics and accelerates the natural occurrence
      of RIDNs. Importantly, we demonstrate that preformed RIDNs appear to reduce
      dendritic spine density and synaptic function. Further analysis from mechanistic
      studies suggests that elevated levels of RTN3 lead to an imbalance in the axonal
      transport of RTN3, which results in the accumulation of RTN3 in swollen neurites.
      Collectively, these results suggest that blocking the formation of RIDNs may be a
      promising strategy to impede cognitive decline in the elderly and in AD patients.

PMID- 19386907
TI  - Dopamine modulation of GABA tonic conductance in striatal output neurons.
AB  - We previously reported greater GABAA receptor-mediated tonic currents in D2+
      striatopallidal than D1+ striatonigral medium spiny neurons (MSNs) are mediated
      by alpha5-subunit-containing receptors. Here, we used whole-cell recordings in
      slices from bacterial artificial chromosome transgenic mice to investigate the
      link between subunit composition, phosphorylation, and dopamine receptor
      activation. Whole-cell recordings in slices from delta-subunit knock-out mice
      demonstrate that while MSNs in wild-type mice do express delta-subunit-containing
      receptors, this receptor subtype is not responsible for tonic conductance
      observed in the acute slice preparation. We assessed the contribution of the
      beta1- and beta3-subunits expressed in MSNs by their sensitivity to etomidate, an
      agonist selective for beta2- or beta3-subunit-containing GABAA receptors.
      Although etomidate produced substantial tonic current in D2+ neurons, there was
      no effect in D1+ neurons. However, with internal PKA application or dopamine
      modulation, D1+ neurons expressed tonic conductance and responded to etomidate
      application. Our results suggest that distinct phosphorylation of beta3-subunits
      may cause larger tonic current in D2+ striatopallidal MSNs, and proper
      intracellular conditions can reveal tonic current in D1+ cells.

PMID- 19386908
TI  - NAD+ activates KNa channels in dorsal root ganglion neurons.
AB  - Although sodium-activated potassium channels (KNa) have been suggested to shape
      various firing patterns in neurons, including action potential repolarization,
      their requirement for high concentrations of Na+ to gate conflicts with this
      view. We characterized KNa channels in adult rat dorsal root ganglion (DRG)
      neurons. Using immunohistochemistry, we found ubiquitous expression of the Slack
      KNa channel subunit in small-, medium-, and large-diameter DRG neurons. Basal KNa
      channel activity could be recorded from cell-attached patches of acutely
      dissociated neurons bathed in physiological saline, and yet in excised inside-out
      membrane patches, the Na+ EC50 for KNa channels was typically high, approximately
      50 mM. In some cases, however, KNa channel activity remained considerable after
      initial patch excision but decreased rapidly over time. Channel activity was
      restored in patches with high Na+. The channel rundown after initial excision
      suggested that modulation of channels might be occurring through a diffusible
      cytoplasmic factor. Sequence analysis indicated that the Slack channel contains a
      putative nicotinamide adenine dinucleotide (NAD+)-binding site; accordingly, we
      examined the modulation of native KNa and Slack channels by NAD+. In inside-out
      excised neuronal patch recordings, we found a decrease in the Na+ EC50 for KNa
      channels from approximately 50 to approximately 20 mM when NAD+ was included in
      the perfusate. NAD+ also potentiated recombinant Slack channel activity. NAD+
      modulation may allow KNa channels to operate under physiologically relevant
      levels of intracellular Na+ and hence provides an explanation as to how KNa
      channel can control normal neuronal excitability.

PMID- 19386909
TI  - Two mechanisms for task switching in the prefrontal cortex.
AB  - Measuring the cognitive and neural sequelae of switching between tasks permits a
      window into the flexible functioning of the executive control system. Prolonged
      reaction times (RTs) after task switches are accompanied by increases in brain
      activity in the anterior cingulate cortex (ACC) and dorsolateral prefrontal
      cortex (dlPFC), but the contribution made by these regions to task level control
      remains controversial. Here, subjects performed a hybrid spatial Stroop/task
      switching paradigm, requiring them to respond with a joystick movement to
      congruent or incongruent spatial/verbal cues. Relative to the previous trial, the
      active task either switched or remained the same. Calculating switch costs as a
      function of current and previous trial congruency, we observed both a general RT
      increase on every switch trial, and additional slowing and impairment to
      performance when the switch occurred on the second of two successive incongruent
      trials (iI trials). Imaging data revealed corresponding neural concomitants of
      these two switch costs: the ACC was activated by task switches regardless of
      trial type (including congruent trials in which task-relevant and task-irrelevant
      information did not clash), whereas the caudal dlPFC exhibited a switch cost that
      was unique to iI trials. We argue that the ACC configures the priorities
      associated with a new task, whereas the dlPFC tackles interference from recently
      active, rivalrous task sets. These data contribute to a literature arguing that
      human cognitive flexibility benefits from the setting of new priorities for
      future action as well as the overcoming of interference from previously active
      task sets.

PMID- 19386910
TI  - Sleep promotes the neural reorganization of remote emotional memory.
AB  - Sleep promotes memory consolidation, a process by which fresh and labile memories
      are reorganized into stable memories. Emotional memories are usually better
      remembered than neutral ones, even at long retention delays. In this study, we
      assessed the influence of sleep during the night after encoding onto the neural
      correlates of recollection of emotional memories 6 months later. After incidental
      encoding of emotional and neutral pictures, one-half of the subjects were allowed
      to sleep, whereas the others were totally sleep deprived, on the first
      postencoding night. During subsequent retest, functional magnetic resonance
      imaging sessions taking place 3 d and 6 months later, subjects made recognition
      memory judgments about the previously studied and new pictures. Between these
      retest sessions, all participants slept as usual at home. At 6 month retest,
      recollection was associated with significantly larger responses in subjects
      allowed to sleep than in sleep-deprived subjects, in the ventral medial
      prefrontal cortex (vMPFC) and the precuneus, two areas involved in memory
      retrieval, as well as in the extended amygdala and the occipital cortex, two
      regions the response of which was modulated by emotion at encoding. Moreover, the
      functional connectivity was enhanced between the vMPFC and the precuneus, as well
      as between the extended amygdala, the vMPFC, and the occipital cortex in the
      sleep group relative to the sleep-deprived group. These results suggest that
      sleep during the first postencoding night profoundly influences the long-term
      systems-level consolidation of emotional memory and modifies the functional
      segregation and integration associated with recollection in the long term.

PMID- 19386911
TI  - Cross-seeding fibrillation of Q/N-rich proteins offers new pathomechanism of
      polyglutamine diseases.
AB  - A pathological hallmark of the Huntington's disease (HD) is intracellular
      inclusions containing a huntingtin (Htt) protein with an elongated polyglutamine
      tract. Aggregation of mutant Htt causes abnormal protein-protein interactions,
      and the functional dysregulation of aggregate-interacting proteins (AIPs) has
      been proposed as a pathomechanism of HD. Despite this, a molecular mechanism
      remains unknown how Htt aggregates sequester AIPs. We note an RNA-binding
      protein, TIA-1, as a model of AIPs containing a Q/N-rich sequence and suggest
      that in vitro and in vivo Htt fibrillar aggregates function as a structural
      template for inducing insoluble fibrillation of TIA-1. It is also plausible that
      such a cross-seeding activity of Htt aggregates represses the physiological
      function of TIA-1. We thus propose that Htt aggregates act as an intracellular
      hub for the cross-seeded fibrillation of Q/N-rich AIPs and that a cross-seeding
      reaction is a molecular origin to cause diverse pathologies in a polyglutamine
      disease.

PMID- 19386912
TI  - Selective increase in representations of sounds repeated at an ethological rate.
AB  - Exposure to sounds during early development causes enlarged cortical
      representations of those sounds, leading to the commonly held view that the size
      of stimulus representations increases with stimulus exposure. However,
      representing stimuli based solely on their prevalence may be inefficient, because
      many frequent environmental sounds are behaviorally irrelevant. Here, we show
      that cortical plasticity depends not only on exposure time but also on the
      temporal modulation rate of the stimulus set. We examined cortical plasticity
      induced by early exposure to 7 kHz tone pips repeated at a slow (2 Hz), fast (15
      Hz), or ethological (6 Hz) rate. Certain rat calls are modulated near 6 Hz. We
      found that spectral representation of 7 kHz increased only in the ethological
      rate-reared animals, whereas improved entrainment of cortical neurons was seen in
      animals reared in the slow- and fast-rate condition. This temporal rate
      dependence of spectral plasticity may serve as a filtering mechanism to
      selectively enlarge representations of species-specific vocalizations.
      Furthermore, our results indicate that spectral and temporal plasticity can be
      separately engaged depending on the statistical properties of the input stimuli.

PMID- 19386913
TI  - Ventral mesencephalon-enriched genes that regulate the development of
      dopaminergic neurons in vivo.
AB  - Mesodiencephalic dopaminergic (mDA) neurons are critical for movement control and
      other physiological activities. However, the molecular mechanisms underlying
      their development are poorly understood. We aimed to establish the expression
      profiles of genes involved in this process and unravel genetic programs that
      control late development of mDA neurons. We compared genome-wide gene expression
      profiles of developing mouse ventral mesencephalon (VM) using microarrays. We
      identified a set of genes that show spatially and temporally restricted
      expression in the VM in an Ngn2 (neurogenin 2)-dependent manner and are
      potentially important for mDA neuron development. Functional analysis on mice
      lacking the VM-specific gene early B-cell factor 1 (Ebf1) revealed that Ebf1 is
      essential for the terminal migration of mDA neurons in the substantia nigra pars
      compacta. Thus, we identified a set of VM-enriched genes that are important for
      mDA neuron development. Our analysis also provides a genetic framework for
      further investigation of the molecular mechanisms mediating mDA neuron
      development.

PMID- 19386914
TI  - A novel function for p53: regulation of growth cone motility through interaction
      with Rho kinase.
AB  - The transcription factor p53 suppresses tumorgenesis by regulating cell
      proliferation and migration. We investigated whether p53 could also control cell
      motility in postmitotic neurons. p53 isoforms recognized by phospho-p53-specific
      (at Ser-15) or "mutant" conformation-specific antibodies were highly and
      specifically expressed in axons and axonal growth cones in primary hippocampal
      neurons. Inhibition of p53 function by inhibitors, small interfering RNAs, or by
      dominant-negative forms, induced axonal growth cone collapse, whereas p53
      overexpression led to larger growth cones. Furthermore, deletion of the p53
      nuclear export signal blocked its axonal distribution and induced growth cone
      collapse. p53 inhibition-induced axonal growth cone collapse was significantly
      reduced by the Rho kinase (ROCK) inhibitor, Y27632 [(R)-(+)-trans-N-(4-pyridyl)-4
      (1-aminoethyl)-cyclohexanecarboxamide]. Our results reveal a new function for p53
      as a critical regulator of axonal growth cone behavior by suppressing ROCK
      activity.

PMID- 19386915
TI  - Cerebellar neurons possess a vesicular compartment structurally and functionally
      similar to Glut4-storage vesicles from peripheral insulin-sensitive tissues.
AB  - The insulin-sensitive isoform of the glucose transporting protein, Glut4, is
      expressed in fat as well as in skeletal and cardiac muscle and is responsible for
      the effect of insulin on blood glucose clearance. Recent studies have revealed
      that Glut4 is also expressed in the brain, although the intracellular
      compartmentalization and regulation of Glut4 in neurons remains unknown. Using
      sucrose gradient centrifugation, immunoadsorption and immunofluorescence
      staining, we have shown that Glut4 in the cerebellum is localized in
      intracellular vesicles that have the sedimentation coefficient, the buoyant
      density, and the protein composition similar to the insulin-responsive Glut4
      storage vesicles from fat and skeletal muscle cells. In cultured cerebellar
      neurons, insulin stimulates glucose uptake and causes translocation of Glut4 to
      the cell surface. Using 18FDG (18fluoro-2-deoxyglucose) positron emission
      tomography, we found that physical exercise acutely increases glucose uptake in
      the cerebellum in vivo. Prolonged physical exercise increases expression of the
      Glut4 protein in the cerebellum. Our results suggest that neurons have a novel
      type of translocation-competent vesicular compartment which is regulated by
      insulin and physical exercise similar to Glut4-storage vesicles in peripheral
      insulin target tissues.

PMID- 19386916
TI  - Polarity-sensitive modulation of cortical neurotransmitters by transcranial
      stimulation.
AB  - Transcranial direct current stimulation (tDCS) modulates cortical excitability
      and is being used for human studies more frequently. Here we probe the underlying
      neuronal mechanisms by measuring polarity-specific changes in neurotransmitter
      concentrations using magnetic resonance spectroscopy (MRS). MRS provides evidence
      that excitatory (anodal) tDCS causes locally reduced GABA while inhibitory
      (cathodal) stimulation causes reduced glutamatergic neuronal activity with a
      highly correlated reduction in GABA, presumably due to the close biochemical
      relationship between the two neurotransmitters.

PMID- 19386917
TI  - Caenorhabditis elegans innexins regulate active zone differentiation.
AB  - In a genetic screen for active zone defective mutants in Caenorhabditis elegans,
      we isolated a loss-of-function allele of unc-7, a gene encoding an
      innexin/pannexin family gap junction protein. Innexin UNC-7 regulates the size
      and distribution of active zones at C. elegans neuromuscular junctions. Loss-of
      function mutations in another innexin, UNC-9, cause similar active zone defects
      as unc-7 mutants. In addition to presumptive gap junction localizations, both UNC
      7 and UNC-9 are also localized perisynaptically throughout development and
      required in presynaptic neurons to regulate active zone differentiation. Our
      mosaic analyses, electron microscopy, as well as expression studies suggest a
      novel and likely nonjunctional role of specific innexins in active zone
      differentiation in addition to gap junction formations.

PMID- 19386918
TI  - Phase-resetting curves determine synchronization, phase locking, and clustering
      in networks of neural oscillators.
AB  - Networks of model neurons were constructed and their activity was predicted using
      an iterated map based solely on the phase-resetting curves (PRCs). The
      predictions were quite accurate provided that the resetting to simultaneous
      inputs was calculated using the sum of the simultaneously active conductances,
      obviating the need for weak coupling assumptions. Fully synchronous activity was
      observed only when the slope of the PRC at a phase of zero, corresponding to
      spike initiation, was positive. A novel stability criterion was developed and
      tested for all-to-all networks of identical, identically connected neurons. When
      the PRC generated using N-1 simultaneously active inputs becomes too steep, the
      fully synchronous mode loses stability in a network of N model neurons.
      Therefore, the stability of synchrony can be lost by increasing the slope of this
      PRC either by increasing the network size or the strength of the individual
      synapses. Existence and stability criteria were also developed and tested for the
      splay mode in which neurons fire sequentially. Finally, N/M synchronous
      subclusters of M neurons were predicted using the intersection of parameters that
      supported both between-cluster splay and within-cluster synchrony. Surprisingly,
      the splay mode between clusters could enforce synchrony on subclusters that were
      incapable of synchronizing themselves. These results can be used to gain insights
      into the activity of networks of biological neurons whose PRCs can be measured.

PMID- 19386919
TI  - Expertise with artificial nonspeech sounds recruits speech-sensitive cortical
      regions.
AB  - Regions of the human temporal lobe show greater activation for speech than for
      other sounds. These differences may reflect intrinsically specialized domain
      specific adaptations for processing speech, or they may be driven by the
      significant expertise we have in listening to the speech signal. To test the
      expertise hypothesis, we used a video-game-based paradigm that tacitly trained
      listeners to categorize acoustically complex, artificial nonlinguistic sounds.
      Before and after training, we used functional MRI to measure how expertise with
      these sounds modulated temporal lobe activation. Participants' ability to
      explicitly categorize the nonspeech sounds predicted the change in pretraining to
      posttraining activation in speech-sensitive regions of the left posterior
      superior temporal sulcus, suggesting that emergent auditory expertise may help
      drive this functional regionalization. Thus, seemingly domain-specific patterns
      of neural activation in higher cortical regions may be driven in part by
      experience-based restructuring of high-dimensional perceptual space.

PMID- 19386921
TI  - Fundamental contribution by the basolateral amygdala to different forms of
      decision making.
AB  - Impairments in decision making about risks and rewards have been observed in
      patients with amygdala damage. Similarly, lesions of the basolateral amygdala
      (BLA) in rodents disrupts cost/benefit decision making, reducing preference for
      larger rewards obtainable after a delay or considerable physical effort. We
      assessed the effects of inactivation of the BLA on risk- and effort-based
      decision making, using discounting tasks conducted in an operant chamber.
      Separate groups of rats were trained on either a risk- or effort-discounting
      task, consisting of four blocks of 10 free-choice trials. Selection of one lever
      always delivered a smaller reward (one or two pellets), whereas responding on the
      other delivered a larger, four pellet reward. For risk discounting, the
      probability of receiving the larger reward decreased across trial blocks (100
      12.5%), whereas on the effort task, the larger reward was delivered after a ratio
      of presses that increased across blocks (2-20). Infusions of GABA agonists
      baclofen/muscimol into the BLA disrupted risk discounting, inducing a risk-averse
      pattern of choice, and increased response latencies and trial omissions, most
      prominently during trial blocks that provided the greatest uncertainty about the
      most beneficial course of action. Similar inactivations also increased effort
      discounting, reducing the preference for larger yet more costly rewards, even
      when the relative delays to reward delivery were equalized across response
      options. These findings point to a fundamental role for the BLA in different
      forms of cost/benefit decision making, facilitating an organism's ability to
      overcome a variety of costs (work, uncertainty, delays) to promote actions that
      may yield larger rewards.

PMID- 19386920
TI  - The ventral premammillary nucleus links fasting-induced changes in leptin levels
      and coordinated luteinizing hormone secretion.
AB  - Physiological conditions of low leptin levels like those observed during negative
      energy balance are usually characterized by the suppression of luteinizing
      hormone (LH) secretion and fertility. Leptin administration restores LH levels
      and reproductive function. Leptin action on LH secretion is thought to be
      mediated by the brain. However, the neuronal population that mediates this effect
      is still undefined. The hypothalamic ventral premammillary nucleus (PMV) neurons
      express a dense concentration of leptin receptors and project to brain areas
      related to reproductive control. Therefore, we hypothesized that the PMV is well
      located to mediate leptin action on LH secretion. To test our hypothesis, we
      performed bilateral excitotoxic lesions of the PMV in adult female rats. PMV
      lesioned animals displayed a clear disruption of the estrous cycle, remaining in
      anestrus for 15-20 d. After apparent recovery of cyclicity, animals perfused in
      the afternoon of proestrus showed decreased Fos immunoreactivity in the
      anteroventral periventricular nucleus and in gonadotropin releasing hormone
      neurons. PMV-lesioned animals also displayed decreased estrogen and LH secretion
      on proestrus. Lesions caused no changes in mean food intake and body weight up to
      7 weeks after surgery. We further tested the ability of leptin to induce LH
      secretion in PMV-lesioned fasted animals. We found that complete lesions of the
      PMV precluded leptin stimulation of LH secretion on fasting. Our findings
      demonstrate that the PMV is a key site linking changing levels of leptin and
      coordinated control of reproduction.

PMID- 19386922
TI  - Neuroprotection by the NR3A subunit of the NMDA receptor.
AB  - Hyperactivation of NMDA-type glutamate receptors (NMDARs) results in
      excitotoxicity, contributing to damage in stroke and neurodegenerative disorders.
      NMDARs are generally comprised of NR1/NR2 subunits but may contain modulatory NR3
      subunits. Inclusion of NR3 subunits reduces the amplitude and dramatically
      decreases the Ca2+ permeability of NMDAR-associated channels in heterologous
      expression systems and in transgenic mice. Since excessive Ca2+ influx into
      neurons is a crucial step for excitotoxicity, we asked whether NR3A subunits are
      neuroprotective. To address this question, we subjected neurons genetically
      lacking NR3A to various forms of excitotoxic insult. We found that cultured
      neurons prepared from NR3A knock-out (KO) mice displayed greater sensitivity to
      damage by NMDA application than wild-type (WT) neurons. In vivo, neonatal, but
      not adult, WT mice contain NR3A in the cortex, and neonatal NR3A KO mice
      manifested more damage than WT after hypoxia-ischemia. In adult retina, one
      location where high levels of NR3A normally persist into adulthood, injection of
      NMDA into the eye killed more retinal ganglion cells in adult NR3A KO than WT
      mice. These data suggest that endogenous NR3A is neuroprotective. We next asked
      whether we could decrease excitotoxicity by overexpressing NR3A. We found that
      cultured neurons expressing transgenic (TG) NR3A displayed greater resistance to
      NMDA-mediated neurotoxicity than WT neurons. Similarly in vivo, adult NR3A TG
      mice subjected to focal cerebral ischemia manifested less damage than WT mice.
      These data suggest that endogenous NR3A protects neurons, and exogenously added
      NR3A increases neuroprotection and could be potentially exploited as a
      therapeutic.

PMID- 19386923
TI  - Learning signals from the superior colliculus for adaptation of saccadic eye
      movements in the monkey.
AB  - Vital to motor learning is information about movement error. Using this
      information, the brain creates neural learning signals that instruct a plasticity
      mechanism to produce appropriate behavioral learning. Little is known, however,
      about brain structures that generate learning signals for voluntary movements.
      Here we show that signals from the superior colliculus (SC) can drive learning in
      saccadic eye movements in the monkey. Electrical stimulation of the SC deeper
      layers, subthreshold for evoking saccades, was applied immediately (approximately
      60 ms) after the end of horizontal saccades in one or both directions. The target
      disappeared during saccades and remained invisible for 1 s to eliminate effects
      of postsaccadic visual information. Repetitive pairing of saccades with SC
      stimulation produced a marked, two-dimensional shift in movement endpoint
      relative to the target location. The elicited endpoint shift took a gradual,
      approximately exponential course over several hundred saccades as in visually
      induced saccade adaptation. The shift in movement endpoint remained nearly
      unchanged after stimulation was discontinued, indicating involvement of neuronal
      plasticity. When both rightward and leftward saccades were paired with
      stimulation, their endpoints shifted in similar directions. The endpoint shift
      was directed contralaterally to the stimulated SC. The direction and size of the
      endpoint shift depended on the stimulation site in the SC. We propose that the
      SC, a brainstem structure long known to be crucial for saccade execution, is
      involved in motor learning and sends signals that dictate the direction of
      adaptive shift in saccade endpoint.

PMID- 19386924
TI  - Gap junctions between striatal fast-spiking interneurons regulate spiking
      activity and synchronization as a function of cortical activity.
AB  - Striatal fast-spiking (FS) interneurons are interconnected by gap junctions into
      sparsely connected networks. As demonstrated for cortical FS interneurons, these
      gap junctions in the striatum may cause synchronized spiking, which would
      increase the influence that FS neurons have on spiking by the striatal medium
      spiny (MS) neurons. Dysfunction of the basal ganglia is characterized by changes
      in synchrony or periodicity, thus gap junctions between FS interneurons may
      modulate synchrony and thereby influence behavior such as reward learning and
      motor control. To explore the roles of gap junctions on activity and spike
      synchronization in a striatal FS population, we built a network model of FS
      interneurons. Each FS connects to 30-40% of its neighbors, as found
      experimentally, and each FS interneuron in the network is activated by simulated
      corticostriatal synaptic inputs. Our simulations show that the proportion of
      synchronous spikes in FS networks with gap junctions increases with increased
      conductance of the electrical synapse; however, the synchronization effects are
      moderate for experimentally estimated conductances. Instead, the main tendency is
      that the presence of gap junctions reduces the total number of spikes generated
      in response to synaptic inputs in the network. The reduction in spike firing is
      due to shunting through the gap junctions; which is minimized or absent when the
      neurons receive coincident inputs. Together these findings suggest that a
      population of electrically coupled FS interneurons may function collectively as
      input detectors that are especially sensitive to synchronized synaptic inputs
      received from the cortex.

PMID- 19386925
TI  - The hippocampus codes the uncertainty of cue-outcome associations: an
      intracranial electrophysiological study in humans.
AB  - Learning to predict upcoming outcomes based on environmental cues is essential
      for adaptative behavior. In monkeys, midbrain dopaminergic neurons code two
      statistical properties of reward: a prediction error at the outcome and
      uncertainty during the delay period between cues and outcomes. Although the
      hippocampus is sensitive to reward processing, and hippocampal-midbrain
      functional interactions are well documented, it is unknown whether it also codes
      the statistical properties of reward information. To address this question, we
      recorded local field potentials from intracranial electrodes in human hippocampus
      while subjects learned to associate cues of slot machines with various monetary
      reward probabilities (P). We found that the amplitudes of negative event-related
      potentials covaried with uncertainty at the outcome, being maximal for P = 0.5
      and minimal for P = 0 and P = 1, regardless of winning or not. These results show
      that the hippocampus computes an uncertainty signal that may constitute a
      fundamental mechanism underlying the role of this brain region in a number of
      functions, including attention-based learning, associative learning,
      probabilistic classification, and binding of stimulus elements.

PMID- 19386926
TI  - Identification of candidate genes and gene networks specifically associated with
      analgesic tolerance to morphine.
AB  - Chronic morphine administration may alter the expression of hundreds to thousands
      of genes. However, only a subset of these genes is likely involved in analgesic
      tolerance. In this report, we used a behavior genetics strategy to identify
      candidate genes specifically linked to the development of morphine tolerance. Two
      inbred genotypes [C57BL/6J (B6), DBA2/J (D2)] and two reciprocal congenic
      genotypes (B6D2, D2B6) with the proximal region of chromosome 10 (Chr10)
      introgressed into opposing backgrounds served as the behavior genetic filter.
      Tolerance after therapeutically relevant doses of morphine developed most rapidly
      in the B6 followed by the B6D2 genotype and did not develop in the D2 mice and
      only slightly in the D2B6 animals indicating a strong influence of the proximal
      region of Chr10 in the development of tolerance. Gene expression profiling and
      pattern matching identified 64, 53, 86, and 123 predisposition genes and 81, 96,
      106, and 82 tolerance genes in the periaqueductal gray (PAG), prefrontal cortex,
      temporal lobe, and ventral striatum, respectively. A potential gene network was
      identified in the PAG in which 19 of the 34 genes were strongly associated with
      tolerance. Eleven of the network genes were found to reside in quantitative trait
      loci previously associated with morphine-related behaviors, whereas seven were
      predictive of tolerance (morphine-naive condition). Overall, the genes modified
      by chronic morphine administration show a strong presence in canonical pathways
      representative of neuroadaptation. A potentially significant role for the micro
      RNA and epigenetic mechanisms in response to chronic administration of
      pharmacologically relevant doses of morphine was highlighted by candidate genes
      Dicer and H19.

PMID- 19386927
TI  - Frontal eye field neurons with spatial representations predicted by their
      subcortical input.
AB  - The frontal eye field (FEF) is a cortical structure involved in cognitive aspects
      of eye movement control. Neurons in the FEF, as in most of cerebral cortex,
      primarily represent contralateral space. They fire for visual stimuli in the
      contralateral field and for saccadic eye movements made to those stimuli. Yet
      many FEF neurons engage in sophisticated functions that require flexible spatial
      representations such as shifting receptive fields and vector subtraction. Such
      functions require knowledge about all of space, including the ipsilateral
      hemifield. How does the FEF gain access to ipsilateral information? Here, we
      provide evidence that one source of ipsilateral information may be the opposite
      superior colliculus (SC) in the midbrain. We physiologically identified neurons
      in the FEF that receive input from the opposite SC, same-side SC, or both. We
      found a striking structure-function relationship: the laterality of the response
      field of an FEF neuron was predicted by the laterality of its SC inputs. FEF
      neurons with input from the opposite SC had ipsilateral fields, whereas neurons
      with input from the same-side SC had contralateral fields. FEF neurons with input
      from both SCs had lateralized fields that could point in any direction. The
      results suggest that signals from the two SCs provide each FEF with information
      about all of visual space, a prerequisite for higher level sensorimotor
      computations.

PMID- 19386928
TI  - Biochemical support for the "threshold" theory of creativity: a magnetic
      resonance spectroscopy study.
AB  - A broadly accepted definition of creativity refers to the production of something
      both novel and useful within a given social context. Studies of patients with
      neurological and psychiatric disorders and neuroimaging studies of healthy
      controls have each drawn attention to frontal and temporal lobe contributions to
      creativity. Based on previous magnetic resonance (MR) spectroscopy studies
      demonstrating relationships between cognitive ability and concentrations of N
      acetyl-aspartate (NAA), a common neurometabolite, we hypothesized that NAA
      assessed in gray and white matter (from a supraventricular slab) would relate to
      laboratory measures of creativity. MR imaging and divergent thinking measures
      were obtained in a cohort of 56 healthy controls. Independent judges ranked the
      creative products of each participant, from which a "Composite Creativity Index"
      (CCI) was created. Different patterns of correlations between NAA and CCI were
      found in higher verbal ability versus lower verbal ability participants,
      providing neurobiological support for a critical "threshold" regarding the
      relationship between intelligence and creativity. To our knowledge, this is the
      first report assessing the relationship between brain chemistry and creative
      cognition, as measured with divergent thinking, in a cohort comprised exclusively
      of normal, healthy participants.

PMID- 19386929
TI  - Long-term plasticity in mouse sensorimotor circuits after rhythmic whisker
      stimulation.
AB  - Mice actively explore their environment by rhythmically sweeping their whiskers.
      As a consequence, neuronal activity in somatosensory pathways is modulated by the
      frequency of whisker movement. The potential role of rhythmic neuronal activity
      for the integration and consolidation of sensory signals, however, remains
      unexplored. Here, we show that a brief period of rhythmic whisker stimulation in
      anesthetized mice resulted in a frequency-specific long-lasting increase in the
      amplitude of somatosensory-evoked potentials in the contralateral primary
      somatosensory (barrel) cortex. Mapping of evoked potentials and intracortical
      recordings revealed that, in addition to potentiation in layers IV and II/III of
      the barrel cortex, rhythmic whisker stimulation induced a decrease of
      somatosensory-evoked responses in the supragranular layers of the motor cortex.
      To assess whether rhythmic sensory input-based plasticity might arise in natural
      settings, we exposed mice to environmental enrichment. We found that it resulted
      in somatosensory-evoked responses of increased amplitude, highlighting the
      influence of previous sensory experience in shaping sensory responses.
      Importantly, environmental enrichment-induced plasticity occluded further
      potentiation by rhythmic stimulation, indicating that both phenomena share common
      mechanisms. Overall, our results suggest that natural, rhythmic patterns of
      whisker activity can modify the cerebral processing of sensory information,
      providing a possible mechanism for learning during sensory perception.

PMID- 19386930
TI  - Dorsal-ventral integration in the recognition of motion-defined unfamiliar faces.
AB  - The primate visual system is organized into two parallel anatomical pathways,
      both originating in early visual areas but terminating in posterior parietal or
      inferior temporal regions. Classically, these two pathways have been thought to
      subserve spatial vision and visual guided actions (dorsal pathway) and object
      identification (ventral pathway). However, evidence is accumulating that dorsal
      visual areas may also represent many aspects of object shape in absence of
      demands for attention or action. Dorsal visual areas exhibit selectivity for
      three-dimensional cues of depth and are considered necessary for the extraction
      of surfaces from depth cues and can carry out cognitive functions with such cues
      as well. These results suggest that dorsal visual areas may participate in object
      recognition, but it is unclear to what capacity. Here, we tested whether three
      dimensional structure-from-motion (SFM) cues, thought to be computed exclusively
      by dorsal stream mechanisms, are sufficient to drive complex object recognition.
      We then tested whether recognition of such stimuli relies on dorsal stream
      mechanisms alone, or whether dorsal-ventral integration is invoked. Results
      suggest that such cues are sufficient to drive unfamiliar face recognition in
      normal participants and that ventral stream areas are necessary for both
      identification and learning of unfamiliar faces from SFM cues.

PMID- 19386931
TI  - Staircase currents in motoneurons: insight into the spatial arrangement of
      calcium channels in the dendritic tree.
AB  - In spinal motoneurons, activation of dendritically located depolarizing
      conductances can lead to amplification of synaptic inputs and the production of
      plateau potentials. Immunohistochemical and computational studies have implicated
      dendritic CaV1.3 channels in this amplification and suggest that CaV1.3 channels
      in spinal motoneurons may be organized in clusters in the dendritic tree. Our
      goal was to provide physiological evidence for the presence of multiple discrete
      clusters of voltage-gated calcium channels in spinal motoneurons and to explore
      the spatial arrangement of these clusters in the dendritic tree. We recorded
      voltage-gated calcium currents from spinal motoneurons in slices of mature mouse
      spinal cords. We demonstrate that single somatic voltage-clamp steps can elicit
      multiple inward currents with varying delays to onset, resulting in a current
      with a "staircase"-like appearance. Recordings from cultured dorsal root ganglion
      cells at different stages of neurite development provide evidence that these
      currents arise from the unclamped portions of the dendritic tree. Finally, both
      voltage- and current-clamp data were used to constrain computer models of a
      motoneuron. The resultant simulations impose two conditions on the spatial
      distribution of CaV channels in motoneuron dendrites: one of asymmetry relative
      to the soma and another of spatial separation between clusters of CaV channels.
      We propose that this compartmentalization would provide motoneurons with the
      ability to process multiple sources of input in parallel and integrate this
      processed information to produce appropriate trains of action potentials for the
      intended motor behavior.

PMID- 19386933
TI  - Creatinine values change when laboratories standardize assay.

PMID- 19386932
TI  - Nucleus accumbens deep brain stimulation produces region-specific alterations in
      local field potential oscillations and evoked responses in vivo.
AB  - Deep brain stimulation of the nucleus accumbens (NAC) region is an effective
      therapeutic avenue for several psychiatric disorders that are not responsive to
      traditional treatment strategies. Nonetheless, the mechanisms by which DBS
      achieves therapeutic effects remain unclear. We showed previously that high
      frequency (HF) NAC DBS suppressed pyramidal cell firing and enhanced slow local
      field potential (LFP) oscillations in the orbitofrontal cortex (OFC) via
      antidromic activation of corticostriatal recurrent inhibition. Using simultaneous
      multisite LFP recordings in urethane-anesthetized rats, we now show that NAC DBS
      delivered for 90 min at high or low frequency (LF) selectively affects
      spontaneous and evoked LFP oscillatory power and coherence within and between the
      medial prefrontal cortex (mPFC), lateral OFC, mediodorsal thalamus (MD), and NAC.
      Compared with LF or sham DBS, HF DBS enhanced spontaneous slow oscillations and
      potentiated evoked LFP responses only in OFC. HF DBS also produced widespread
      increases in spontaneous beta and gamma power and enhanced coherent beta activity
      between MD and all other regions. In contrast, LF DBS elevated theta power in MD
      and NAC. Analysis of acute NAC-induced oscillations showed that HF DBS increased
      and LF DBS decreased induced relative gamma coherence compared with sham DBS.
      These data suggest that HF (therapeutic) and LF (possibly deleterious) NAC DBS
      produce distinct region-specific and frequency band-specific changes in LFP
      oscillations. NAC DBS may achieve therapeutic effects by enhancing rhythmicity
      and synchronous inhibition within and between afferent structures, thereby
      normalizing function of a neural circuit that shows aberrant activity in
      obsessive-compulsive disorder and depression.

PMID- 19386934
TI  - New oral treatment for kidney cancer approved.

PMID- 19386935
TI  - FDA, researchers focus on genetics of drug hypersensitivity.

PMID- 19386936
TI  - Most Wisconsin hospitals adopt standardized color alerts.

PMID- 19386937
TI  - Perception of drug-name legibility by pharmacists and pharmacy technicians.

PMID- 19386938
TI  - Effect of a distraction-free environment on medication errors.

PMID- 19386939
TI  - Difficulty in administration of liquid protein solution via an enteral feeding
      tube.

PMID- 19386940
TI  - Preliminary national survey of pharmacist involvement in trauma resuscitation.

PMID- 19386941
TI  - Recent trends in drug shortages: an update from the 2003 report.

PMID- 19386942
TI  - Use of performance portfolios for pharmacy personnel.

PMID- 19386943
TI  - Whither pharmacy informatics.

PMID- 19386944
TI  - Romiplostim: a novel thrombopoiesis-stimulating agent.
AB  - PURPOSE: The pharmacology, pharmacokinetics, dosage and administration, efficacy,
      safety, effects on quality of life, and place in therapy of romiplostim are
      reviewed. SUMMARY: Romiplostim is a second- generation thrombopoietic agent that
      stimulates the thrombopoietin receptor and platelet production without inducing
      production of autoantibodies. Romiplostim, a peptibody, bears no structural
      resemblance to endogenous thrombopoietin, thus minimizing the risk for
      development of thrombopoietin autoantibodies. Clinical trials have shown that
      romiplostim increases platelet counts compared with placebo in both
      splenectomized and non-splenectomized adult patients with chronic idiopathic
      thrombocytopenic purpura (ITP). Clinical trials with romiplostim are ongoing for
      patients with myelodysplastic syndrome and those receiving chemotherapy for
      treatment of malignancies. Romiplostim may confer an increased risk of bone
      marrow reticulin formation or fibrosis, malignancy, thrombosis, and
      thrombocytopenia that is more severe than the level present before initiation of
      romiplostim. While all patients receiving romiplostim in clinical trials
      experienced at least one adverse event, most were mild to moderate in severity.
      The most frequent adverse effects were ecchymosis, headache, and petechiae.
      Romiplostim is initiated at a dosage of 1 microg/kg subcutaneously once weekly
      and titrated to achieve platelet counts between 50 and 200 x 10(9) platelets/L,
      with a maximum dose of 10 microg/kg. Romiplostim is only available through the
      manufacturer's risk-management program. The current wholesale price of
      romiplostim is $1,062.50 for a single-use vial of 250 microg or $2,125 for a
      single-use vial of 500 microg. The extrapolated drug cost for weekly dosing for
      one year is approximately $55,250. CONCLUSION: Romiplostim is a novel
      thrombopoietic-stimulating agent for use in patients with chronic ITP who have
      not responded to other therapies.

PMID- 19386945
TI  - Methadone-associated Q-T interval prolongation and torsades de pointes.
AB  - PURPOSE: The association of methadone with Q-T interval prolongation and torsades
      de pointes (TdP) is reviewed, and recommendations for preventing Q-T interval
      prolongation in methadone users are provided. SUMMARY: Abnormalities in voltage
      gated potassium channels have been shown to lead to prolonged action potentials
      that are expressed as long Q-T intervals, and methadone has been found to
      interact with the voltage-gated potassium channels of the myocardium. While
      cardiac arrhythmias in methadone users have been reported for several decades,
      specific reports of methadone-associated Q-T interval prolongation and TdP did
      not appear in the literature until the early part of the 21st century. Because
      not every patient experiences Q-T interval prolongation with methadone, recent
      research has elucidated risk factors that predispose patients to this adverse
      effect, including female sex, hypokalemia, high-dose methadone, drug
      interactions, underlying cardiac conditions, unrecognized congenital long Q-T
      interval syndrome, and predisposing DNA polymorphisms. Given the high mortality
      rates seen in untreated illicit opioid users and the clear efficacy of methadone
      in treating opioid addiction, the risk of using methadone, even in a patient with
      other risk factors for Q-T interval prolongation, may outweigh the alternative of
      no pharmacologic treatment. A baseline electrocardiogram (ECG), personal and
      family history of syncope, and a complete medication history should be obtained
      before a patient begins treatment with methadone. Given the apparent synergistic
      effects of parenteral methadone and chlorobutanol, oral methadone should be used
      whenever possible. CONCLUSION: Q-T interval prolongation and TdP associated with
      the use of methadone are potentially fatal adverse effects. A thorough patient
      history and ECG monitoring are essential for patients treated with this agent,
      and alterations in treatment options may be necessary.

PMID- 19386946
TI  - Lepirudin-induced thrombocytopenia following subcutaneous administration.
AB  - PURPOSE: A case of lepirudin-induced thrombocytopenia is reported. SUMMARY: A 61
      year-old white man arrived at the emergency department with complaints of pain in
      his left thigh that worsened with walking. His medical history was significant
      for extensive thromboses over a period of six months. He had recently been
      discharged from the hospital for suspected heparin-induced thrombocytopenia (HIT)
      while on enoxaparin. A venous duplex scan revealed two new deep venous thromboses
      in the left common, superficial, and popliteal veins. The patient was admitted
      and initiated on aspirin 325 mg and warfarin sodium 2 mg daily. Intravenous
      lepirudin with an activated partial thromboplastin time (aPTT) goal of 60-80
      seconds was also started. Because of his recurrent thrombotic event, a new
      International Normalized Ratio (INR) goal of 3.0-3.5 was established for warfarin
      therapy. Eighteen days after admission, the patient's INR and aPTT were high;
      therefore, his warfarin dose was reduced and i.v. lepirudin was changed to
      subcutaneous administration. The patient was transferred to the intensive care
      unit (ICU) and, 5 days later, he developed melena. During the 7 days of treatment
      with subcutaneous lepirudin, a drop in platelet counts was observed. Subcutaneous
      lepirudin was discontinued after resolution of melena, and i.v. lepirudin was
      restarted. After 15 days, his platelet counts increased and he was switched back
      to subcutaneous lepirudin, which again led to a drop in platelets. After 27 days
      in the ICU, the patient's INR and aPTT remained high. Lepirudin was discontinued
      and i.v. bivalirudin was initiated. His platelet count increased and he was
      discharged. Eleven days later, the patient was found unresponsive with left-sided
      fasciculations. The patient died secondary to respiratory arrest as a consequence
      of intracranial hemorrhage. CONCLUSION: A 61-year-old white man with a history of
      thromboses and suspected HIT developed thrombocytopenia possibly associated with
      receiving two courses of subcutaneous lepirudin. Careful monitoring of platelet
      counts are warranted in patients who have a history of HIT and are receiving
      subcutaneous lepirudin.

PMID- 19386947
TI  - Effects of nitazoxanide on pharmacokinetics and pharmacodynamics of a single dose
      of warfarin.
AB  - PURPOSE: The effects of nitazoxanide on warfarin pharmacokinetics and
      pharmacodynamics are examined. METHODS: This was a Phase I, single-center, open
      label, randomized, two-way, crossover study. Secondary endpoints included an
      evaluation of the effect of nitazoxanide on coagulation parameters observed after
      a single dose of warfarin and an assessment of the overall tolerability of study
      treatments. Fourteen healthy men were selected for the study. The study consisted
      of two treatment periods (Treatment A and Treatment B), each lasting 6 days, with
      a washout period of at least 21 days between both warfarin intakes. All subjects
      were scheduled to receive both Treatment A and Treatment B, according to the
      randomization list. Treatment A consisted of a single oral dose of 25 mg warfarin
      sodium (five 5-mg tablets). Treatment B consisted of a single oral intake of 25
      mg warfarin sodium (five 5-mg tablets) and one 500-mg tablet of nitazoxanide
      (with nitazoxanide 500 mg continued twice daily for up to 6 days). RESULTS: All
      14 subjects received Treatment B, and 13 of the 14 subjects received Treatment A.
      Pharmacokinetic results were similar in both treatments, and pharmacodynamic
      parameters were similar in both treatments. Fourteen adverse events occurred in
      eight subjects after administration of at least one dose of the study drug.
      Eleven adverse events occurred in six subjects after treatment with warfarin and
      nitazoxanide, and three adverse events occurred in two subjects after treatment
      with warfarin alone. At discharge, a high hemoglobin level and a low total
      bilirubin level were reported in both groups. CONCLUSION: Coadministration of
      nitazoxanide twice daily for six days did not affect the pharmacokinetic or
      pharmacodynamic properties of a single 25-mg dose of warfarin sodium.
      Administration of a single dose of warfarin or combined administration of a
      single dose of warfarin and multiple doses of nitazoxanide appeared safe and well
      tolerated.

PMID- 19386948
TI  - Medication errors resulting from computer entry by nonprescribers.
AB  - PURPOSE: The characteristics of medication errors associated with the use of
      computer order-entry systems by nonprescribers are discussed. METHODS: A
      retrospective analysis of records submitted to MEDMARX was conducted for the
      period from July 1, 2001, to December 31, 2005, to identify all computer-related
      medication errors made by nonprescribers. Quantitative analysis of the records
      included the severity of each error, the origin within the medication-use
      process, the type of error, principal causes, the location within the facility
      where the error was made, and the therapeutic drug classes frequently involved.
      Similar data from the University of Pittsburgh Medical Center (UPMC) were also
      analyzed and compared with the national data set. RESULTS: During the 4.5 years,
      693 unique facilities submitted 90,001 medication error records that were the
      result of computer entry by nonprescribers. The national data set and the UPMC
      data had similar findings for error severity, error origin, and type of error but
      showed some differences in the rank ordering of error causes, location where the
      error occurred, and drug classes frequently associated with such errors. The
      percentage of harm associated with computer-entry errors was small for both the
      national data set and UPMC data (0.99% and 0.80%, respectively). Both data sets
      cited performance deficit as the leading cause of computer-entry errors, but
      large percentage differences were seen with other causes, including inaccurate or
      omitted transcription (30% versus 12.6%, respectively), documentation (19.5%
      versus 10.6%, respectively), and procedure or protocol not followed (21.7% versus
      30.3%, respectively). Both data sets implicated the inpatient pharmacy department
      as the location where most computer-entry errors occurred (49.3% versus 69.0%,
      respectively). CONCLUSION: Analysis of the characteristics of medication errors
      associated with the use of computer-entry systems by non-prescribers from both
      MEDMARX and an individual health system database demonstrated that computer
      systems create new opportunities for errors to occur. Working closely with
      information technology personnel dedicated to assisting pharmacy departments and
      vendors, adequate training of pharmacy staff, and development of national
      standards for drug information displays in computer order-entry systems may help
      minimize such errors.

PMID- 19386949
TI  - Effects of an integrated medicines management program on medication
      appropriateness in hospitalized patients.
AB  - PURPOSE: The effects of an integrated medicines management (IMM) program on
      medication appropriateness are discussed. METHODS: Patients enrolled in an IMM
      project within a hospital were randomly allocated to either a control or an
      intervention group. Patients in the control group received standard
      pharmaceutical care, while the intervention patients received the IMM service.
      The appropriateness of the medications prescribed was estimated on admission and
      discharge using the Medicines Appropriateness Index (MAI), which ranged from 0
      (no prescribing problems) to 18 (most prescribing problems). For each medication
      scored, the difference between admission and discharge MAI scores for individual
      patients was calculated. RESULTS: Scoring was completed on 1711 medications
      prescribed for 117 patients. There was a statistically significant difference (p
      = 0.03) in the mean MAI scores on discharge between the intervention and control
      groups (5.69 versus 9.97, respectively). There was also a statistically
      significant difference (p = 0.00003) in the mean MAI scores on admission and
      discharge (17.48 versus 5.69, respectively) for the intervention group. The
      intervention group had a mean +/- S.D. difference of -11.78 +/- 14.64, while the
      control group had a mean +/- S.D. difference of -3.19 +/- 11.80. The difference
      was statistically significant (p = 0.0011) between the two groups. CONCLUSION:
      This study demonstrated significant improvements in the appropriateness of
      medications on discharge for patients receiving an IMM service compared with
      patients who did not receive this service.

PMID- 19386950
TI  - Stability of fentanyl 5 microg/mL diluted with 0.9% sodium chloride injection and
      stored in polypropylene syringes.
AB  - PURPOSE: The stability of fentanyl 5 microg/mL in 0.9% sodium chloride solution
      packaged in polypropylene syringes was studied. METHODS: Samples of fentanyl 5
      microg (as the citrate) per milliliter in 0.9% sodium chloride injection were
      prepared and assessed for chemical stability using a validated, stability
      indicating high- performance liquid chromatographic (HPLC) assay. A total of 12
      syringe samples were submitted for chemical stability testing by HPLC. The
      syringes were protected from light and stored in controlled ambient conditions
      (23-27 degrees C and 55-65% relative humidity) in an environmental chamber. Three
      samples were tested initially and at each 30-day interval. Each syringe sample
      was tested with two determinations, using the average of the determinations for
      the assay result. Samples were assessed for pH and inspected for color and
      visible particulate matter. Stability was defined as the retention of 90-110% of
      the initial drug concentration at 30, 60, and 90 days. RESULTS: Fentanyl citrate
      injection maintained the appearance of a clear, colorless solution, with mean +/-
      S.D. pH values ranging from 4.13 +/- 0.01 to 4.52 +/- 0.02 throughout the study
      period. Recovery of fentanyl ranged from 99.86% +/- 0.29% to 102.74% +/- 1.60% of
      the initial concentration, with no detectable changes in the chromatographic
      profiles of all tested samples. CONCLUSION: Fentanyl 5 microg (as the citrate)
      per milliliter in 0.9% sodium chloride injection, packaged in polypropylene
      syringes and stored protected from light, was stable for at least 90 days in
      controlled ambient conditions.

PMID- 19386951
TI  - Implications of recent clinical trials on pay-for-performance.

PMID- 19386952
TI  - Klippel-Trenaunay syndrome with hemimegalencephaly, retroperitoneal lymphangioma
      and double inferior vena cava.
AB  - Klippel-Trenaunay syndrome (KTS) is a rare disorder characterised by congenital
      vascular hamartomas, limb hypertrophy, lymphangiomas and atresia of lymph vessels
      with non-pitting oedema. A 6-year-old girl with KTS was referred to our hospital
      for evaluation of intractable seizures. In addition to findings consistent with
      KTS, we also found hemimegalencephaly, retroperitoneal lymphangioma and double
      inferior vena cava. All of these associations in the same patient with KTS are
      unique in the English literature. We report on the multidedector CT and MRI
      features of such an unusual case.

PMID- 19386953
TI  - Testicular seminoma with mediastinal lymphadenopathy -- a diagnostic pitfall.
AB  - Relapse following adjuvant paraaortic radiation therapy in patients with Stage I
      seminoma is rare, occurring in approximately 4% of men. The majority of relapses
      are sited in the pelvis but relapse in the mediastinum is also recognised. As
      such, radiological imaging using chest radiographs remains commonplace in follow
      up. However, there are reports of the association of testicular cancers with
      sarcoidosis and sarcoid-like processes in the mediastinum, emphasising the
      importance of making histological diagnosis prior to commencement of any
      treatment. We report on two men treated for testicular seminoma who on follow-up
      developed mediastinal lymphadenopathy, which was initially assumed to be
      metastatic seminoma. Both patients underwent mediastinascopy and biopsy prior to
      commencement of anti-cancer therapy. In both cases, the biopsies showed
      sarcoidosis, and unnecessary anti-cancer treatment was avoided.

PMID- 19386954
TI  - Early failure of a Birmingham resurfacing hip replacement with lymphoreticular
      spread of metal debris: pre-operative diagnosis with MR.
AB  - Metal-on-metal hip replacements are the subject of much current debate. There is
      some evidence that there may be a hypersensitivity reaction, specific to metal-on
      metal total hip replacements (THRs), which is associated with early failure of
      these prostheses. It has to date only been described in total replacements and
      not in metal-on-metal hip resurfacing. We present the case of a 68-year-old man
      who underwent bilateral metal-on-metal hip resurfacing for osteoarthrosis. The
      patient presented 6 months after surgery with pain and lateral thigh swelling.
      Pre-operative ultrasound and MRI demonstrated findings similar to those described
      in early failing metal-on-metal THRs, as well as evidence of lymphoreticular
      spread of metal debris. The operative findings included extensive aseptic soft
      tissue necrosis. Histology revealed necrosis and a dense perivascular lymphocytic
      infiltrate along with metal debris within sinus histiocytes. The surgical,
      radiological and histological findings are similar to soft-tissue reactions
      described in metal-on-metal THRs.

PMID- 19386955
TI  - A pain in the neck -- an unexpected complication of transrectal ultrasound and
      biopsy.
AB  - In the UK, over 26 000 cases of prostate cancer are diagnosed annually, with many
      more patients undergoing investigation. Prostate-specific antigen (PSA) testing
      and its interpretation has always been controversial. Many patients undergo PSA
      driven biopsies, which can cause significant morbidity. We report an unusual but
      severe complication following transrectal ultrasound and biopsy.

PMID- 19386956
TI  - MDCT findings of acute aortic dissection with diastolic prolapse of the intimal
      flap into the left ventricle.
AB  - Acute aortic regurgitation is frequently recognised in patients with Stanford
      Type A aortic dissection. However, diastolic prolapse of the aortic intimal flap
      into the left ventricle can cause aortic regurgitation in rare cases. Here is
      presented an image report of severe aortic regurgitation that was secondary to
      the back-and-forth intimal flap movement of acute Type A aortic dissection by the
      use of transthoracic echocardiography and multidetector row CT.

PMID- 19386957
TI  - Gastrointestinal stromal tumour with a KIT exon 11 mutation presenting as a
      paratesticular mass.
AB  - Gastrointestinal stromal tumours (GISTs) are sarcomas arising in the
      gastrointestinal tract. They are characterised by a gain in function mutation of
      the KIT oncogene and the majority express the receptor tyrosine kinase KIT, which
      can be detected by the immunohistochemical stain CD117. Patients with a GIST
      present with symptoms such as abdominal pain or gastrointestinal bleeding, or may
      be asymptomatic. We describe the clinical history and pathological features of a
      patient with a GIST who presented with a paratesticular mass which, to our
      knowledge, has never previously been reported. With the development of new drugs
      to treat GISTs, the knowledge of the type of mutations may in the future prove
      helpful in determining optimal treatment strategies and prognosis.

PMID- 19386958
TI  - 21st L H Gray Conference: the radiobiology/radiation protection interface.
AB  - The 21st L H Gray Conference, organised by the L H Gray Trust with the Society
      for Radiological Protection, brought together international experts in
      radiobiology, epidemiology and risk assessment, and scientists involved in
      diagnostic and therapeutic radiation exposure. The meeting - held in Edinburgh,
      Scotland, on 4-6 June 2008 - aimed to raise awareness, educate and share
      knowledge of important issues in radiation protection. A distinguished group of
      speakers discussed topics that included (i) non-targeted effects of radiation,
      (ii) exposure to high natural background radiation, (iii) non-cancer effects in
      Japanese bomb survivors, (iv) lessons learnt from Chernobyl, (v) radiation in the
      workplace, (vi) biokinetic modelling, (vii) uncertainties in risk estimation,
      (viii) issues in diagnostic medical exposures, (ix) lessons leant from the
      polonium-210 incidence and (x) how the radiobiology/radiation oncology community
      is needed to help society prepare for potential future acts of radiation
      terrorism. The conference highlighted the importance, relevance and topicality of
      radiobiology today.

PMID- 19386959
TI  - The use of gonad shielding in paediatric hip and pelvis radiographs.
AB  - The problem of inaccurate placement of gonad shields in children has been
      highlighted by several publications nationally and internationally over the past
      decade and more. Here, we review the literature and present the results of a
      regional audit designed to assess the use and accuracy of placement of gonad
      shields for hip and pelvis radiographs in children. 100 consecutive
      anteroposterior hip or pelvis radiographs in patients under the age of 16 years
      were reviewed in each of 9 centres. We also included the most recent and all
      previously available relevant radiographs. A total of 2405 radiographs were
      reviewed with regard to the presence of a shield and to the accuracy of any
      shield placement with respect to gonad protection and visualization of
      orthopaedic landmarks. It is recommended that gonad shields are used in all
      follow-up paediatric pelvis radiographs. Our results show they were only used in
      70% of such cases. When placed, only 38% of all shields were considered to be
      positioned accurately. For cases where shielding was indicated, an accurately
      placed shield was present in just 26% of radiographs. Formal written departmental
      guidelines for shield use were only available in two centres. We conclude that
      clear guidelines need to be formulated which, together with shield redesign,
      improved training and audit, should increase effective gonad protection for
      children.

PMID- 19386960
TI  - The use of time to maximum enhancement to indicate areas of ablation following
      the treatment of liver tumours with high-intensity focused ultrasound.
AB  - The aim of this study was to investigate the use of time to maximum enhancement
      (t(max)) for each voxel in contrast-enhanced MRI (CE-MRI) as a non-invasive tool
      to determine areas of necrosis following treatment of liver tumours with high
      intensity focused ultrasound (HIFU) and, having established the utility of t(max)
      maps, to develop a three-dimensional (3-D) representation to display this
      information concisely. 3-D T(1) weighted fast spoiled gradient echo images of the
      liver were acquired before and after administration of contrast agent. The CE-MR
      images were aligned to the pre-contrast volume and an estimate of t(max) was
      obtained for each voxel. Such pre- and post-contrast image sets were acquired
      before and after ablation. The t(max) maps before and after HIFU treatment were
      correlated with the procedure notes, radiological reports and gross histological
      specimen. Finally, 3-D t(max) maps of the whole liver were reconstructed to show
      all areas of abnormal tissue perfusion. Normal, healthy liver tissue uniformly
      enhances maximally after approximately 1 min. The computed t(max) maps accurately
      delineated areas of abnormal contrast agent uptake, corresponding to tumour
      deposits. Changes in t(max) and non-enhancing voxels after treatment correlate
      well with volumes targeted during ablation and the necrotic regions seen on gross
      histological specimens. Alignment of the contrast-enhanced images with the pre
      contrast volume greatly improved the conspicuity of the t(max) maps. We conclude
      that t(max) maps and their 3-D views can be used as a non-invasive tool to assess
      and potentially to quantify the success of HIFU ablation, and concisely represent
      the large number of CE-MRI data.

PMID- 19386961
TI  - Differential diagnosis of hyperintense cerebrospinal fluid on fluid-attenuated
      inversion recovery images of the brain. Part I: pathological conditions.
AB  - The fluid-attenuated inversion recovery imaging sequence is a widely used MRI
      sequence of the brain. It is an inversion recovery pulse sequence, designed to
      suppress signals from the cerebrospinal fluid. It is highly sensitive in
      detection of lesions adjacent to or within the cerebrospinal fluid associated
      with T(2) prolongation or T(1) shortening. The term "hyperintense cerebrospinal
      fluid" is used to describe failed suppression, or hyperintensity, of
      cerebrospinal fluid on fluid-attenuated inversion recovery imaging of the brain.
      It is often encountered in many important pathological conditions, including
      subarachnoid haemorrhage, meningitis and leptomeningeal metastasis. However,
      certain non-pathological states in which there is no definite cerebrospinal fluid
      abnormality can also present with hyperintense cerebrospinal fluid. Correct
      interpretation of abnormalities is important to arrive at an appropriate
      diagnosis. This pictorial review provides fluid-attenuated inversion recovery
      images of hyperintense cerebrospinal fluid of the brain and describes
      distinguishing features. Part I features pathological conditions whereas Part II
      focuses on non-pathological conditions.

PMID- 19386962
TI  - A curious mass of the anterior compartment in the knee.

PMID- 19386963
TI  - Interference of gadolinium-based contrast agents with the measurement of serum
      creatinine by the Jaffe reaction.

PMID- 19386964
TI  - Increase in clinical prevalence of AIDS implies increase in unsafe medical
      injections.
AB  - A mass action model developed by the World Health Organization (WHO) estimates
      that the re-use of contaminated syringes for medical care accounted for 2.5% of
      HIV infections in sub-Saharan Africa in 2000. The WHO's model applies the
      population prevalence of HIV infection rather than the clinical prevalence to
      calculate patients' frequency of exposure to contaminated injections. This
      approach underestimates iatrogenic exposure risks when progression to advanced
      HIV disease is widespread. This sensitivity analysis applies the clinical
      prevalence of HIV to the model and re-evaluates the transmission efficiency of
      HIV in injections. These adjustments show that no less than 12-17%, and up to 34
      47%, of new HIV infections in sub-Saharan Africa may be attributed to medical
      injections. The present estimates undermine persistent claims that injection
      safety improvements would have only a minor impact on HIV incidence in Africa.

PMID- 19386965
TI  - IUSTI: 2008 European Guidelines on the Management of Syphilis.

PMID- 19386966
TI  - Relationship between heterosexual anal sex, injection drug use and HIV infection
      among black men and women.
AB  - US blacks carry a disproportionate risk of heterosexually transmitted HIV. This
      study aimed to evaluate the association between self-reported heterosexual anal
      intercourse and HIV. Using respondent-driven sampling (RDS), we recruited and
      interviewed 909 blacks from areas of high poverty and HIV prevalence in Houston,
      Texas, and who reported heterosexual sex in the last year. All individuals were
      tested for HIV. Weighted prevalence values were calculated to account for non
      random recruitment associated with RDS. The weighted population prevalence of HIV
      infection was 2.4% and 2.5% among men and women, respectively. Education,
      employment status, income and crack cocaine use were not associated with HIV
      infection. Lifetime injection drug use (odds ratio [OR] 3.31, 95% confidence
      interval [CI] 1.31-8.33%) and heterosexual anal intercourse (OR 2.41, 95% CI 1.02
      5.73%) were associated with HIV infection. Individuals who reported both
      injection drug use and heterosexual anal intercourse had 6.21 increased odds of
      HIV (95% CI 2.47-15.61%). Our results suggest that heterosexual anal sex may be a
      vector for HIV transmission, especially in the context of injection drug use.
      Prevention strategies directed at curbing the HIV epidemic among black
      heterosexuals require that we correctly identify the risks so that appropriate
      interventions can be developed.

PMID- 19386967
TI  - Diagnosis, management and prevalence estimation of gonorrhoea: influences of
      Aptima Combo 2 assay with alternative target confirmation.
AB  - Case-notes and laboratory data were retrospectively reviewed for influences of
      dual testing by Aptima Combo 2 (AC2) for Chlamydia trachomatis (CT) and Neisseria
      gonorrhoeae (NG) on the diagnosis, management and prevalence estimation of
      gonorrhoea in the genitourinary (GU) medicine clinic and community. NG positives
      by AC2 were confirmed by Aptima Gonococcus assay. Unconfirmed positives were
      rare. Our study showed that in the GU medicine clinic, AC2 detected about 20%
      extra cases of NG beyond culture. For best standard of care, NG culture and
      microscopy are still required in some patients to ensure that treatment is rapid
      and appropriate. Compared to self-referral at the GU medicine clinic, community
      tests made a substantial contribution to the overall number of NG cases found (40
      community versus 35 Macclesfield GU medicine clinic). The ratio of female to male
      NG cases found was significantly higher (P = 0.002) in the community (13 M, 27 F)
      than at the GU medicine clinic (25 M, 10 F). In the community, over 60% of NG
      infections occurred in chlamydia-negative patients. The overall prevalence of NG
      in the GU medicine clinic was 1.3%, the true prevalence being much lower at 0.9%
      on primary test. Prevalence in the community was 0.4%. Data from dual testing in
      the community can clarify NG prevalence beyond the existing KC60 (sexually
      transmitted infections) reports.

PMID- 19386968
TI  - Drug abuse profile - patient delay, diagnosis delay and drug resistance pattern -
      among addict patients with tuberculosis.
AB  - Socioeconomic problems limit the access of drug users to health-care services.
      This descriptive cross-sectional study was carried out by making use of the
      medical records of new case tuberculosis (TB) patients hospitalized at Masih
      Daneshvari Hospital, the national referral centre in Iran, from 2003 to 2006.
      Demographic and personal characteristics of the patients and type of disease were
      collected and categorized. Of the 944 patients with confirmed TB, 143 (15.1%)
      were drug users, among whom 140 (97.9%) were men with just three women drug
      users. The mean age of the drug users group was 43.04 +/- 13.81 years. The type
      of drug used was opium in 100 cases (69.9%), heroin in 29 (20.3%), opium and
      heroin together in four (2.8%) and all three, opium, heroin and crack, in two
      (1.4%). For 238 high-risk patients, an HIV test was performed and HIV infection
      was confirmed in 33 cases. Patient delay was longer in drug users (P = 0.000)
      against other patients, whereas diagnosis delay was shorter (P = 0.007). Drug
      susceptibility tests were performed for 515 patients with positive cultures. One
      hundred and thirty-three (14.1%) were found to have 'any resistance' to anti-TB
      drugs, and 10 (1.1%) individuals had multidrug-resistant TB. Twenty-six (19.5%)
      of the individuals who showed resistance to first-line agents were drug users.
      There was no significant relation between drug resistance and drug use (P = 0.4).
      In conclusion, it seems that active case finding for TB and HIV in addict cases
      must be contained in harm reduction packages. Moreover, the manifestations of the
      disease should be considered seriously regardless of attributing them to drug
      use.

PMID- 19386969
TI  - How do UK medical graduates rate their knowledge and skills in sexual health and
      HIV medicine? A national survey.
AB  - The objectives of this study are to determine self-assessed knowledge and skills
      in sexual health and HIV medicine in preregistration house officers and to
      explore undergraduate experiences of teaching and assessment in these subjects
      prior to the launch of National Core Learning Outcomes in Sexual and Reproductive
      Health and HIV. The study was designed as a postal questionnaire survey. The
      participants were all UK medical graduates of August 2004. The response rate
      1737/4746 (36%). The main outcome measures were Doctors' views on their
      preparedness to manage patients with sexual health and HIV-related problems.
      Since graduation, 90% of respondents had seen at least one patient with a
      sexually transmitted infection or HIV-related issue. Seventy-six percent felt
      confident to take a sexual history. In all, 63% and 53% felt competent in male
      and female genital examination, respectively. Forty-three percent felt they could
      conduct an appropriate HIV pretest discussion and 59% felt they could recognize
      clinical indicators suggestive of HIV. Seventy-eight percent had been formally
      assessed in sexual health and 55% in HIV medicine. Increased confidence in sexual
      history taking, HIV pretest discussion and recognition of HIV indicators was
      associated with a longer duration of teaching and formal examination. In
      conclusion, although the proportion of recent graduates confident in sexual
      history taking is encouraging, their lack of skill in discussing HIV testing,
      risk assessment and recognition of possible HIV presentations must be addressed.
      Integration of National Core Learning Outcomes into all undergraduate curricula
      is a key step in reducing inconsistencies in undergraduate training.

PMID- 19386970
TI  - A novel use of AIDS surveillance data to assess the impact of initial treatment
      regimen on survival.
AB  - The expense in time and money limit the use of randomized clinical trials (RCT)
      and cohort studies for evaluating long-term AIDS treatment outcomes. We conducted
      a case-control study to characterize predictors of AIDS mortality after the
      availability of highly active antiretroviral therapy (HAART) in San Francisco, in
      which cases were matched with controls on stage of disease, year of AIDS
      diagnosis and year of HAART initiation. Overall, 266 cases and 1173 controls were
      included, representing >90% of eligible patients. The class of initial HAART
      regimen was not associated with mortality. Predictors of mortality were older age
      ([adjusted odds ratio] AOR 1.23, 95% [confidence interval] CI: 1.13-1.35), public
      versus private health insurance (AOR 2.80, 95% CI: 1.77-4.42), no versus private
      insurance (AOR 1.45, 95% CI: 1.02-2.07) and unboosted saquinavir (AOR 2.50, 95%
      CI: 1.34-4.65). Survival benefit was found in following the 2004 US Department of
      Health and Human Services preferred treatment guidelines; borderline survival
      benefits were found in following the guidelines from other years. Similar
      predictors were found for all-cause and AIDS-specific mortality. Our findings
      mirrored those of RCT and multi-centre cohort studies, and may be applicable to
      other settings. Our findings support similar survival benefit to persons
      initiating HAART with non-nucleoside reverse transcriptase inhibitor- or protease
      inhibitor-based regimens.

PMID- 19386971
TI  - Frequency of isolated hepatitis B core antibody in HIV-hepatitis C virus co
      infected individuals.
AB  - Association between isolated hepatitis B core antibody (anti-HBc) and hepatitis C
      virus (HCV) infection has been noted in HIV-infected individuals. This study
      describes the frequency of isolated anti-HBc and its possible value for the
      detection of HBV-DNA in HIV-infected patients with or without HCV co-infection.
      Ninety-two HIV-infected patients were enrolled in the study. Hepatitis B surface
      antigen (HBs Ag), anti-HBs, anti-HBc, anti-HCV, HIV viral load and CD4 count were
      tested in all subjects. Then we compared 63 subjects with HIV-HCV co-infection
      with 29 subjects with HIV infection alone regarding isolated anti-HBc (HBs Ag
      negative, anti-HBs negative and anti-HBc positive). The presence of HBV-DNA was
      determined by real-time polymerase chain reaction in serum samples of patients
      with isolated anti-HBc. Of 63 anti-HCV-positive patients, 18 subjects (28.6%, 95%
      [confidence interval] CI: 22.6-34.6%), and of 29 anti-HCV-negative patients, five
      subjects (17.2%, 95% CI: 11.5-22.9%) had isolated anti-HBc. HBV-DNA was
      detectable in three of 18 anti-HCV-positive patients (16.7%, 95% CI: 9.7-23.7%)
      and none of the anti-HCV-negative patients with isolated anti-HBc. Our study
      showed that individuals co-infected with HIV and HCV were more likely to have
      isolated anti-HBc than subjects with HIV alone. This investigation also
      demonstrates that the presence of isolated anti-HBc in HIV-HCV-infected
      individuals may reflect occult HBV infection in these patients.

PMID- 19386972
TI  - Adverse events to antituberculosis therapy: influence of HIV and antiretroviral
      drugs.
AB  - This study investigated whether serious adverse events (SAEs) during
      antituberculosis therapy occur more frequently in HIV co-infected patients in a
      South African population. A retrospective analysis examined incidences of
      hepatotoxicity, peripheral neuropathy, severe arthralgia, persistent vomiting and
      severe rash in 400 patients treated for tuberculosis in a community clinic. A
      total of 141 patients were co-infected with HIV, among whom only 16.3% were
      receiving antiretrovirals. Details of SAEs were ascertainable in 331/400
      patients, and occurred in 26.7% of HIV-infected and 13.3% of HIV-uninfected
      individuals (P = 0.003). The excess was attributable to increased peripheral
      neuropathy (8.3% and 1.9%, respectively, P = 0.009) and persistent vomiting
      (13.3% and 3.3%, P = 0.001). SAE occurrence was not related to antiretroviral
      use, although median CD4 counts were lower in those experiencing side-effects
      (130 and 259 cells/microL, P = 0.008). The treatment completion did not differ
      significantly between the two groups (76.6% and 84.2%, P = 0.08).

PMID- 19386973
TI  - A survey of Cambodian health-care providers' HIV knowledge, attitudes and
      intentions to take a sexual history.
AB  - Cambodia has one of the highest prevalence rates of HIV in Asia and is scaling up
      HIV testing. We conducted a cross-sectional survey with 358 health care providers
      in Phnom Penh, Cambodia to assess readiness for voluntary testing and counselling
      for HIV. We measured HIV knowledge and attitudes, and predictors of intentions to
      take a sexual history using the Theory of Planned Behaviour. Over 90% of health
      care providers correctly answered knowledge questions about HIV transmission, but
      their attitudes were often not positive towards people living with HIV. The
      Theory of Planned Behaviour constructs explained 56% of the variance in intention
      to take a sexual history: the control providers perceive they have over taking a
      sexual history was the strongest contributor (51%), while social pressure
      explained a further 3%. Attitudes about taking a sexual history did not
      contribute to intention. Interventions with Cambodian health care providers
      should focus on improving skills in sexual history-taking.

PMID- 19386974
TI  - UK National Audit of Sexual History-taking: case-notes audit.
AB  - A national audit of sexual history-taking was conducted in genitourinary medicine
      clinics in the UK in 2008. Data were aggregated by region and clinic, allowing
      practice to be compared between regions, as well as to national averages and
      against national Guidelines. In this paper the case-notes of 4121 patients were
      audited. A high proportion of the case-notes were deemed to be completely
      legible. In other respects there is considerable inter-regional variation in the
      adherence to national Guidelines. Interventions are especially required to
      improve documentation of practice in discussing condom use, HIV risk assessment,
      offer of a chaperone and assessment for hepatitis B vaccination and hepatitis C
      testing, and issues concerning sexual contacts.

PMID- 19386975
TI  - UK National Audit of Sexual History-taking: clinic policies audit.
AB  - Provision of a confidential, private environment for sexual history-taking was
      provided in almost all clinics. However, less than half of the clinics had a
      policy displayed about their confidentiality policy in waiting areas, although
      more had this available by other means. About two-thirds of clinic
      information/advertising literature included information about the need to take a
      sexual history. Sixty percent of clinics assessed clinician communication skills
      as part of service quality. Most clinics had policies relating to patients whose
      first language is not English, but only around half of clinics had policies for
      hearing difficulties and learning difficulties. Policies are also lacking in some
      clinics for documentation of the offer of chaperones and assessment of the
      competency of under-16-year-olds to consent to history-taking and examination.

PMID- 19386976
TI  - Concordance between nucleic acid amplification technique and culture for the
      diagnosis of gonorrhoea.
AB  - The objective of the study was to evaluate the concordance between nucleic acid
      amplification technique (NAAT) and culture for the diagnosis of Neisseria
      gonorrhoeae among attendees at a genitourinary medicine clinic in East London.
      All patients testing positive for N. gonorrhoeae on NAAT and/or culture between 1
      April 2007 and 31 August 2008 at the Department of Sexual Health at Homerton
      University Hospital were included. Male patients had a first void urine sample
      for NAAT and urethral culture; female patients had a self-taken vulval swab or
      endocervical sample sent for NAAT and an endocervical culture sample. After
      interim analysis, discrepant results had both NAAT and culture repeated prior to
      treatment. Of 159 male patients with a positive NAAT, 22 (13%) had a negative
      culture. Among 135 female patients with a positive NAAT, 36 (27%) had a negative
      culture. Three men had a positive culture and negative NAAT. Nineteen of the
      discrepant samples were retested prior to treatment and 12 (63%) had
      spontaneously revered to negative. In conclusion, there was concordance in 84% of
      male and 67% of female samples. In two-thirds of the discrepant cases, the
      previously positive NAAT had become negative prior to treatment. This study
      highlights the importance of consideration of the clinical picture when assessing
      results.

PMID- 19386977
TI  - Chlamydia screening programme, HMP Hydebank Wood Young Offender Centre, Belfast,
      Northern Ireland, UK.
AB  - In a young offender's centre, 204 male prisoners were offered chlamydia
      screening, from January 2007 to April 2007. The aim of this screening programme
      was to identify and treat asymptomatic prisoners with chlamydia infection.
      Offering the screening within a prison was an opportunity to test a hard-to-reach
      population that is at high risk of chlamydia infection. The programme established
      a high level of testing acceptability with a 98% screening uptake rate. Using
      nucleic acid amplification testing, 21 (10.5%) tested prisoners were positive for
      Chlamydia trachomatis. Patients were treated under Patient Group Direction (PGD).
      Further screening for sexually transmitted diseases was offered to chlamydia
      positive patients by the genitourinary (GU) medicine specialist.

PMID- 19386978
TI  - Threadworm: an infrequent clinical finding in a genitourinary medicine clinic
      attendee presenting with ano-genital irritation.
AB  - A 24-year-old lady presented to an evening genitourinary (GU) clinic with a short
      history of vulval and anal irritation. On perianal examination, several
      threadworms were visible. Symptoms resolved with oral mebendazole and strict
      personal and environmental hygiene. Threadworm is a common and easily treatable
      cause of pruritus ani, yet is underreported in GU literature. If the history is
      suggestive, consider performing the diagnostic cellophane test and/or prescribing
      empirical treatment.

PMID- 19386979
TI  - What attracts trainees to genitourinary medicine?

PMID- 19386980
TI  - Quality enhancements and quality assurance of laboratory diagnosis of sexually
      transmitted infections in Eastern Europe.

PMID- 19386981
TI  - Is the service of HIV counselling and testing satisfied in Hangzhou, China?

PMID- 19386982
TI  - Activin A, activin receptor type II, nodal, and cripto mRNA are expressed by
      eutopic and ectopic endometrium in women with ovarian endometriosis.
AB  - Activin A is a dimeric protein that regulates endometrial functions by signaling
      at its receptors, namely type I (ActRI) and type II (ActRII). Nodal is an activin
      competitor that requires the coreceptor cripto to assemble its signaling pathway
      through ActRI and ActRII. In the current study, we evaluated the expression of
      activin A, ActRII, nodal, and cripto in eutopic and ectopic endometrium collected
      from women with ovarian endometrioma (n = 15) and in eutopic endometrium of
      healthy participants (n = 15). Eutopic endometrial samples were evaluated
      according to the stage of menstrual cycle. Total RNA was extracted from tissue
      homogenates and analyzed by real-time polymerase chain reaction (PCR). Activin A
      messenger RNA (mRNA) expression in eutopic endometrium of patients with
      endometriosis was significantly higher than in controls (P < .001) with a 10.2
      fold and 7.3-fold increase in the proliferative and secretory phases,
      respectively. ActRII and nodal mRNA expression were found to be similar in
      patients with and without endometriosis, while cripto mRNA was markedly lower in
      eutopic (fold change = 0.03 at proliferative phase, P < .001) and ectopic
      endometrium (fold change = 0.14, P < .001) of women with endometriosis compared
      with eutopic endometrium from healthy controls. In conclusion, the altered
      endometrial expression of activin A and cripto during the menstrual cycle and the
      differences observed in the endometriotic tissue support the involvement of the
      activin system in endometrial changes of women with endometriosis.

PMID- 19386983
TI  - Cortisol and corticosterone in immune organs and brain of European starlings:
      developmental changes, effects of restraint stress, comparison with zebra
      finches.
AB  - Glucocorticoids (GCs) are produced in the adrenal glands and also in extra
      adrenal sites, including immune organs and brain. Here, we examined regulation of
      systemic GC levels in plasma and local GC levels in immune organs and brain
      during development. We conducted two studies and examined a total of 462 samples
      from 70 subjects. In study 1, we determined corticosterone and cortisol levels in
      the plasma, immune organs, and brain of wild European starlings on posthatch day
      0 (P0) and P10 (at baseline and after 45 min of restraint). Baseline
      corticosterone and cortisol levels were low in the immune organs and brain at P0
      and P10, providing little evidence for local GC synthesis in starlings. At P0,
      restraint had no significant effects on corticosterone or cortisol levels in the
      plasma or tissues; however, there was a trend for restraint to increase both
      corticosterone and cortisol in the immune organs. At P10, restraint increased
      corticosterone levels in the plasma and all tissues, but restraint increased
      cortisol levels in the plasma, thymus, and diencephalon only. In study 2, we
      directly compared GC levels in European starlings and zebra finches at P4. In
      zebra finches but not starlings, cortisol levels were higher in the immune organs
      than in plasma. This difference in immune GC levels might be due to evolutionary
      lineage, life history strategy, or experiential factors, such as parasite
      exposure. This is the first study to measure immune GC levels in wild animals and
      one of the first studies to measure local GC levels after restraint stress.

PMID- 19386984
TI  - Marinobufagenin causes endothelial cell monolayer hyperpermeability by altering
      apoptotic signaling.
AB  - Marinobufagenin (MBG) is an endogenous mammalian cardiotonic steroid that is
      involved in the inhibition of the sodium pump Na(+)/K(+)-ATPase. Increased plasma
      levels of MBG have been reported in patients with preeclampsia. MBG increases
      microvascular barrier permeability in an animal model of preeclampsia. However,
      the mechanism by which MBG impairs endothelial permeability is unknown. We
      utilized rat lung microvascular endothelial cells (RLMEC) to examine alterations
      in MBG-induced monolayer permeability and the effect of MBG on the
      phosphorylation status of ERK1/2, Jnk, and p38. Apoptosis was evaluated by
      examining alterations in caspases 3/7, 8, and 9 and annexin-V staining. We also
      examined the effect of MBG on the endothelial adherens junctions of the RLMEC
      monolayer. MBG inhibited the proliferation, and increased the monolayer
      permeability, of RLMEC. These actions of MBG were attenuated by ERK, p38, and pan
      caspase inhibition. MBG significantly decreased the phosphorylation of ERK1/2 and
      activated the phosphorylation of Jnk and p38. MBG also significantly increased
      the expression of caspases 3/7, 8, and 9, indicating the activation of apoptosis.
      MBG-induced apoptosis signaling was not observed in cells pretreated with a p38
      inhibitor. MBG treatment induced the disruption of endothelial cell junctions.
      This effect was prevented by a pan caspase inhibitor. In conclusion, 1) MBG
      induced an impairment of RLMEC proliferation; 2) the bufadienolide also caused
      endothelial hyperpermeability; and 3) these effects of MBG were mediated by the
      downregulation of ERK1/2, the upregulation of Jnk and p38, by the activation of
      apoptosis, and by the disruption of endothelial cell junctions.

PMID- 19386985
TI  - High glucose concentration in cell culture medium does not acutely affect human
      mesenchymal stem cell growth factor production or proliferation.
AB  - Optimizing the function and proliferative capacity of stem cells is essential to
      maximize their therapeutic benefits. High glucose concentrations are known to
      have detrimental effects on many cell types. We hypothesized that human
      mesenchymal stem cells (hMSCs) cultured in high glucose-containing media would
      exhibit diminished proliferation and attenuated production of VEGF, hepatocyte
      growth factor (HGF), and FGF2 in response to treatment with TNF-alpha, LPS, or
      hypoxia. hMSCs were plated in medium containing low (5.5 mM) and high (20 mM or
      30 mM) glucose concentrations and treated with TNF-alpha, LPS, or hypoxia.
      Supernatants were collected at 24 and 48 h and assayed via ELISA for VEGF, HGF,
      and FGF2. In addition, hMSCs were cultured on 96-well plates at the above glucose
      concentrations, and proliferation at 48 h was determined via bromo-2'-deoxy
      uridine (BrdU) incorporation. At 24 and 48 h, TNF-alpha, LPS, and hypoxia-treated
      hMSCs produced significantly higher VEGF, HGF, and FGF2 compared with control.
      Hypoxia-induced VEGF production by hMSCs was the most pronounced change over
      baseline. At both 24 and 48 h, glucose concentration did not affect production of
      VEGF, HGF, or FGF2 by untreated hMSCs and those treated with TNF-alpha, LPS, or
      hypoxia. Proliferation of hMSCs as determined via BrdU incorporation was
      unaffected by glucose concentration of the media. Contrary to what has been
      observed with other cells, hMSCs may be resistant to the short-term effects of
      high glucose. Ongoing efforts to characterize and optimize ex vivo and in vivo
      conditions are critical if the therapeutic benefits of MSCs are to be maximized.

PMID- 19386986
TI  - Dorsomedial medullary 5-HT2 receptors mediate immediate onset of initial
      hyperventilation, airway dilation, and ventilatory decline during hypoxia in
      mice.
AB  - The dorsomedial medulla oblongata (DMM) includes the solitary tract nucleus and
      the hypoglossal nucleus, to which 5-HT neurons project. Effects of 5-HT in the
      DMM on ventilatory augmentation and airway dilation are mediated via 5-HT2
      receptors, which interact with the CO(2) drive. The interaction may elicit cycles
      between hyperventilation with airway dilation and hypoventilation with airway
      narrowing. In the present study, effects of 5-HT2 receptors in the DMM on hypoxic
      ventilatory and airway responses were investigated, while 5-HT release in the DMM
      was monitored. Adult male mice were anesthetized, and then a microdialysis probe
      was inserted into the DMM. The mice were placed in a double-chamber
      plethysmograph. After recovery from anesthesia, the mice were exposed to hypoxic
      gas (7% O(2) in N(2)) for 5 min with or without a 5-HT2 receptor antagonist (LY
      53857) perfused in the DMM. 5-HT release in the DMM was increased by hypoxia
      regardless of the presence of LY-53857. Immediate onset and the peak of initial
      hypoxic hyperventilatory responses were delayed. Subsequent ventilatory decline
      and airway dilation during initial hypoxic hyperventilation were suppressed with
      LY-53857. These results suggest that 5-HT release increased by hypoxia acts on 5
      HT2 receptors in the DMM, which contributes to the immediate onset of initial
      hypoxic hyperventilation, airway dilation, and subsequent ventilatory decline.
      Hypoxic ventilatory and airway responses mediated via 5-HT2 receptors in the DMM
      may play roles in immediate rescue and defensive adaptation for hypoxia and may
      be included in periodic breathing and the pathogenesis of obstructive sleep
      apnea.

PMID- 19386987
TI  - High-fat feeding increases insulin receptor and IRS-1 coimmunoprecipitation with
      SOCS-3, IKKalpha/beta phosphorylation and decreases PI-3 kinase activity in
      muscle.
AB  - Suppressor of cytokine signaling (SOCS) proteins and/or activation of the
      proinflammatory pathway have been postulated as possible mechanisms that may
      contribute to skeletal muscle insulin resistance. Thus, the aims of the present
      investigation were to determine in high-fat-fed skeletal muscle: 1) whether SOCS
      3 protein concentration is increased, 2) whether coimmunoprecipitation of SOCS-3
      with the insulin receptor-beta subunit and/or IRS-1 is increased, and 3) whether
      select components of the proinflammatory pathway are altered. Thirty-two male
      Sprague-Dawley rats were assigned to either control (CON, n = 16) or high-fat-fed
      (HF, n = 16) dietary groups for 12 wk and then subjected to hind limb perfusions
      in the presence (n = 8/group) or absence (n = 8/group) of insulin. Insulin
      stimulated skeletal muscle 3-MG transport rates and PI-3 kinase activity were
      greater (P < 0.05) in CON. IRS-1 tyrosine phosphorylation was decreased (P <
      0.05), and IRS-1 serine 307 phosphorylation was increased (P < 0.05) in HF.
      Insulin receptor-beta (IR-beta) subunit coimmunoprecipitation with IRS-1 was
      reduced in HF. SOCS-3 protein concentration and SOCS-3 coimmunoprecipitation with
      both the IR-beta subunit and IRS-1 was increased (P < 0.05) in HF. IKKalpha/beta
      serine phosphorylation was increased (P < 0.05), IkappaBalpha protein
      concentration was decreased (P < 0.05) and IkappaBalpha serine phosphorylation
      was increased (P < 0.05) in HF. Increased colocalization of SOCS-3 with both the
      IR-beta subunit and IRS-1 may provide steric hindrance that prevents IRS-1 from
      interacting with IR-beta, while increased IKKbeta serine phosphorylation may
      contribute to increasing IRS-1 serine phosphorylation, both of which
      independently can have deleterious effects on insulin-stimulated PI-3 kinase
      activation in high-fat-fed rodent skeletal muscle.

PMID- 19386989
TI  - B-type natriuretic peptide 8-32, which is produced from mature BNP 1-32 by the
      metalloprotease meprin A, has reduced bioactivity.
AB  - 32-amino acid B-type natriuretic peptide (BNP 1-32) plays an important role in
      cardiovascular homeostasis. Recently, it was reported that BNP 1-32 is cleaved by
      the metalloprotease meprin A to BNP 8-32, the bioactivity of which is undefined.
      We hypothesized that BNP 8-32 has reduced vasodilating and natriuretic
      bioactivity compared with BNP 1-32 in vivo. Human BNP 8-32 and BNP 1-32 were
      compared in a crossover study in eight anesthetized normal canines. After a
      preinfusion clearance, BNP 1-32 was infused at 30 ng.kg(-1) x min(-1) for 45 min
      followed by a 60-min washout and a second preinfusion clearance. Then, equimolar
      BNP 8-32 was infused. In half of the studies, the peptide sequence was reversed.
      Changes with peptides from the respective preinfusion clearance to infusion
      clearance were compared with paired tests. Mean arterial pressure was reduced by
      both BNP 8-32 and BNP 1-32 (-8 +/- 3 vs. -6 +/- 2 mmHg, P = 0.48). Changes in
      right atrial pressure, pulmonary capillary wedge pressure, heart rate, cardiac
      output, and glomerular filtration rate were similar. However, urinary sodium
      excretion increased less with BNP 8-32 than with BNP 1-32 (+171 +/- 24 vs. +433
      +/- 43 muEq/min; P = 0.008), as did urinary potassium excretion, urine flow, and
      renal blood flow. While BNP 8-32 has similar vasodilating actions as BNP 1-32,
      its diuretic and natriuretic actions are reduced, suggesting a role for meprin A
      in the regulation of BNP 1-32 bioactivity in the kidney. Meprin A inhibition may
      be a potential strategy to increase the bioactivity of endogenous and exogenous
      BNP 1-32 in cardiovascular diseases.

PMID- 19386988
TI  - Integration of skeletal muscle resistance arteriolar reactivity for perfusion
      responses in the metabolic syndrome.
AB  - Previous study suggests that with evolution of the metabolic syndrome, patterns
      of arteriolar reactivity are profoundly altered and may constrain functional
      hyperemia. This study investigated interactions between parameters of vascular
      reactivity at two levels of resistance arterioles in obese Zucker rats (OZR),
      translating these observations into perfusion regulation for in situ skeletal
      muscle. Dilation of isolated and in situ resistance arterioles from OZR to
      acetylcholine, arachidonic acid (AA), and hypoxia (isolated arterioles only) were
      blunted vs. lean Zucker rats (LZR), although dilation to adenosine was intact.
      Increased adrenergic tone (phenylephrine) or intralumenal pressure (ILP) impaired
      dilation in both strains (OZR>LZR). Treatment of OZR arterioles with Tempol
      (superoxide dismutase mimetic) or SQ-29548 (prostaglandin H2/thromboxane A2
      receptor antagonist) improved dilator reactivity under control conditions and
      with increased ILP, but had minimal effect with increased adrenergic tone.
      Arteriolar dilation to adenosine was well maintained in both strains under all
      conditions. For in situ cremasteric arterioles, muscle contraction-induced
      elevations in metabolic demand elicited arteriolar dilations and hyperemic
      responses that were blunted in OZR vs. LZR, although distal parallel arterioles
      were characterized by heterogeneous dilator and perfusion responses. alpha
      Adrenoreceptor blockade improved outcomes at rest but had minimal effect with
      elevated metabolic demand. Treatment with Tempol or SQ-29548 had minimal impact
      at rest, but lessened distal arteriolar perfusion heterogeneity with increased
      metabolic demand. In blood-perfused gastrocnemius of OZR, perfusion was
      constrained primarily by adrenergic tone, while myogenic activation and
      endothelium-dependent dilation did not appear to contribute significantly to
      ischemia. These results of this novel, integrated approach suggest that
      adrenergic tone and metabolic dilation are robust determinants of bulk perfusion
      to skeletal muscle of OZR, while endothelial dysfunction may more strongly
      regulate perfusion distribution homogeneity via the impact of oxidant stress and
      AA metabolism.

PMID- 19386990
TI  - Expression regulation of Na+-K+-ATPase alpha1-subunit subtypes in zebrafish gill
      ionocytes.
AB  - In zebrafish (Danio rerio), six distinct Na+-K+-ATPase (NKA) alpha1-subunit genes
      have been identified, and four of them, zatp1a1a.1, zatp1a1a.2, zatp1a1a.4, and
      zatp1a1a.5, are expressed in embryonic skin where different types of ionocytes
      appear. The present study attempted to test a hypothesis of whether these NKA
      alpha1 paralogues are specifically expressed and function in respective
      ionocytes. Double fluorescence in situ hybridization analysis demonstrated the
      specific expression of zatp1a1a.1, zatp1a1a.2, and zatp1a1a.5 in NKA-rich (NaR)
      cells, Na+-Cl- cotransporter (NCC)-expressing cells, and H+-ATPase-rich (HR)
      cells, respectively, based on the colocalization of the three NKA alpha1 genes
      with marker genes of the respective ionocytes (epithelial Ca2+ channel in NaR
      cells; NCC in NCC cells; and H+-ATPase and Na+/H+ exchanger 3b in HR cells). The
      mRNA expression (by real-time PCR) of zatp1a1a.1, zatp1a1a.2, and zatp1a1a.5
      were, respectively, upregulated by low-Ca2+, low-Cl-, and low-Na+ freshwater,
      which had previously been reported to stimulate uptake functions of Ca2+, Cl-,
      and Na+. However, zatp1a1a.4 was not colocalized with any of the three types of
      ionocytes, nor did its mRNA respond to the ambient ions examined. Taken together,
      zATP1a1a.1, zATP1a1a.2, and zATP1a1a.5 may provide driving force for Na+-coupled
      cotransporter activity specifically in NaR, NCC, and HR cells, respectively.

PMID- 19386991
TI  - Significant improvement in cloning efficiency of an inbred miniature pig by
      histone deacetylase inhibitor treatment after somatic cell nuclear transfer.
AB  - The National Institutes of Health (NIH) miniature pig was developed specifically
      for xenotransplantation and has been extensively used as a large-animal model in
      many other biomedical experiments. However, the cloning efficiency of this pig is
      very low (<0.2%), and this has been an obstacle to the promising application of
      these inbred swine genetics for biomedical research. It has been demonstrated
      that increased histone acetylation in somatic cell nuclear transfer (SCNT)
      embryos, by applying a histone deacetylase (HDAC) inhibitor such as trichostatin
      A (TSA), significantly enhances the developmental competence in several species.
      However, some researchers also reported that TSA treatment had various
      detrimental effects on the in vitro and in vivo development of the SCNT embryos.
      Herein, we report that treatment with 500 nM 6-(1,3-dioxo-1H, 3H
      benzo[de]isoquinolin-2-yl)-hexanoic acid hydroxyamide (termed scriptaid), a novel
      HDAC inhibitor, significantly enhanced the development of SCNT embryos to the
      blastocyst stage when NIH inbred fetal fibroblast cells (FFCs) were used as
      donors compared with the untreated group (21% vs. 9%, P < 0.05). Scriptaid
      treatment resulted in eight pregnancies from 10 embryo transfers (ETs) and 14
      healthy NIH miniature pigs from eight litters, while no viable piglets (only
      three mummies) were obtained from nine ETs in the untreated group. Thus,
      scriptaid dramatically increased the cloning efficiency when using inbred
      genetics from 0.0% to 1.3%. In contrast, scriptaid treatment decreased the
      blastocyst rate in in vitro fertilization embryos (from 37% to 26%, P < 0.05). In
      conclusion, the extremely low cloning efficiency in the NIH miniature pig may be
      caused by its inbred genetic background and can be improved by alteration of
      genomic histone acetylation patterns.

PMID- 19386992
TI  - Histone H2A has a novel variant in fish oocytes.
AB  - Histone variants and their modification have significant roles in many cellular
      processes. In this study, we identified and characterized the histone H2A variant
      h2af1o in fish and revealed its oocyte-specific expression pattern during
      oogenesis and embryogenesis. Moreover, posttranslational modification of H2af1o
      was observed that results from phosphorylation during oocyte maturation. To
      understand the binding dynamics of the novel core histone variant H2af1o in
      nucleosomes, we cloned ubiquitous gibel carp h2afx as a conventional histone
      control and investigated the dynamic exchange difference in chromatin by
      fluorescence recovery after photobleaching. H2af1o has significantly higher
      mobility in nucleosomes than ubiquitous H2afx. Compared with ubiquitous H2afx,
      H2af1o has a tightly binding C-terminal and a weakly binding N-terminal. These
      data indicate that fish oocytes have a novel H2A variant that destabilizes
      nucleosomes by protruding its N-terminal tail and stabilizes core particles by
      contracting its C-terminal tail. Our findings suggest that H2af1o may have
      intrinsic ability to modify chromatin properties during fish oogenesis, oocyte
      maturation, and early cleavage.

PMID- 19386993
TI  - Three-dimensional structure of the cytoskeleton in Trichomonas vaginalis revealed
      new features.
AB  - The flagellated protozoan Trichomonas vaginalis has been widely studied owing to
      its medical significance and unique structure. The complicated three-dimensional
      (3D) structure of the cellular components of T. vaginalis was reconstructed from
      serial sections to enable observation of the spatial features of the whole cell.
      Electron tomography was used to examine the detailed structure of the cellular
      organelles. Tomographic reconstruction showed the mastigont system and the
      parabasal filament of T. vaginalis in detail. The last thin filament (Pf3) was
      located close to the adjacent filament, and the two filaments appeared to be
      vertically parallel in the cross-sectional view. It is likely that Pf3 cannot be
      distinguished from the adjacent filament in 2D images obtained from transmission
      electron microscopy. Our 3D reconstruction of T. vaginalis revealed the presence
      of an additional striated fiber, and 3D reconstruction by electron tomography
      showed twisting of the split parabasal filament.

PMID- 19386994
TI  - The role of grief in dementia caregiving.
AB  - The literature examining issues of caregiver stress, burden,or depression has
      focused on the stress-process model of caregiving, which posits that there are
      characteristics inherent in dementia and in the course of caregiving for a person
      with dementia that can cause stress in the caregiver's life. A more recent
      literature has emerged that argues that issues of loss and grief play a
      significant role ina caregiver's ability to cope with the stressors of
      caregiving. This article reviews the caregiver stress and grief literatures,and
      proposes a conceptual model of dementia caregiving that outlines pathways of
      stress and grief in dementia caregiving. Issues specific to caregiver grief are
      proposed for future research and intervention design.

PMID- 19386995
TI  - Variation on a theme: identifying sequence variation in disease genes and
      defining pathogenicity.

PMID- 19386996
TI  - NSAID exposure and risk of Alzheimer disease: is timing everything?

PMID- 19386998
TI  - Human dignity and human rights as a common ground for a global bioethics.
AB  - The principle of respect for human dignity plays a crucial role in the emerging
      global norms relating to bioethics, in particular in the UNESCO Universal
      Declaration on Bioethics and Human Rights. This instrument, which is a legal, not
      merely an ethical document, can be regarded as an extension of international
      human rights law into the field of biomedicine. Although the Declaration does not
      explicitly define human dignity, it would be a mistake to see the emphasis put on
      this notion as a mere rhetorical strategy. Rather, the appeal to dignity reflects
      a real concern about the need to promote respect both for the intrinsic worth of
      human beings and for the integrity of the human species. But dignity alone cannot
      solve most of the dilemmas posed by biomedical practice. This is why
      international biolaw combines, on the one hand, the appeal to human dignity as an
      overarching principle with, on the other hand, the recourse to human rights,
      which provide an effective and practical way forward for dealing with bioethical
      issues at a global level.

PMID- 19386997
TI  - Risk of dementia and AD with prior exposure to NSAIDs in an elderly community
      based cohort.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent Alzheimer
      dementia (AD). METHODS: We analyzed the association of prior NSAID exposure with
      incident dementia and AD in the Adult Changes in Thought population-based cohort
      aged > or = 65 years (median 74.8) at enrollment. Participants were members of
      Group Health, which provided computerized pharmacy dispensing records from 1977
      onward. We studied 2,736 dementia-free enrollees with extensive prior pharmacy
      data, following them biennially for up to 12 years to identify dementia and AD.
      Cox proportional hazards regression assessed association of dementia or AD with
      NSAID use graded in standard daily doses (SDD) dispensed over 2 years (e.g.,
      heavy use = 500 + SDD), with some analyses also adding consecutive biennial self
      reports of NSAID use. RESULTS: Pharmacy records identified 351 participants
      (12.8%) with history of heavy NSAID use at enrollment. Another 107 became heavy
      users during follow-up. Some 476 individuals developed incident dementia, 356
      with AD (median onset ages 83.5 and 83.8 years). Contrary to the hypothesis that
      NSAIDs protect against AD, pharmacy-defined heavy NSAID users showed increased
      incidence of dementia and AD, with adjusted hazard ratios of 1.66 (95% confidence
      interval, 1.24-2.24) and 1.57 (95% confidence interval, 1.10-2.23). Addition of
      self-reported exposure data did not alter these results. CONCLUSIONS: These
      findings differ from those of other studies with younger cohorts. The results
      observed elsewhere may reflect delayed onset of Alzheimer dementia (AD) in
      nonsteroidal anti-inflammatory drug (NSAID) users. Conceivably, such delay could
      result in increased AD incidence in late old age. The relation of NSAID use and
      AD pathogenesis needs further investigation.

PMID- 19386999
TI  - UNESCO, "universal bioethics," and state regulation of health risks: a
      philosophical critique.
AB  - The United Nations Educational, Scientific, and Cultural Organization's (UNESCO)
      Universal Declaration on Bioethics and Human Rights announces a significant array
      of welfare entitlements--to personal health and health care, medicine, nutrition,
      water, improved living conditions, environmental protection, and so forth--as
      well as corresponding governmental duties to provide for such public health
      measures, though the simple expedient of announcing that such entitlements are
      "basic human rights." The Universal Declaration provides no argument for the
      legitimacy of the sweeping governmental authority, taxation, and regulation to
      create and impose such "rights." As this paper explores that some action promotes
      a purported good, such as "health," does not thereby make the action morally
      permissible. Just as there are moral limits on legitimate personal actions, there
      are also moral limits on legitimate governmental actions to promote purported
      goods, including health. A core question of any governmental regulation,
      therefore, is whether it is a legitimate application of moral political authority
      or an unauthorized act of state coercion. Pace UNESCO's wide-ranging assertions,
      this paper argues that promoting health only falls within the legitimate
      authority of governments in very narrowly defined circumstances. As the paper
      critically explores, at stake are foundational moral and political questions
      concerning the limits of governmental authority to intervene in the consensual
      interaction of persons. Imposing such duties on others, including citizens of a
      state through regulatory activity and taxation, must be justified, nonarbitrary,
      and demonstrably within the limits of moral political authority. UNESCO's
      assertions do not meet this burden of proof.

PMID- 19387000
TI  - Solidarity and the Universal Declaration on Bioethics and Human Rights.
AB  - Recent work has stressed the importance of the concept of solidarity to bioethics
      and social philosophy generally. But can and should it feature in documents such
      as the Universal Declaration on Bioethics and Human Rights as anything more than
      a vague notion with multiple possible interpretations? Although noting the
      tension between universality and particularity that such documents have to deal
      with, and also noting that solidarity has a political content, the paper explores
      the suggestion that solidarity should feature more centrally in international
      regulations. The paper concludes with the view that when solidarity is seen
      aright, the UDBHR is an implicitly solidaristic document.

PMID- 19387001
TI  - Bioethics as public discourse and second-order discipline.
AB  - Bioethics is best viewed as both a second-order discipline and also part of
      public discourse. Since their goals differ, some bioethical activities are more
      usefully viewed as advancing public discourse than academic disciplines. For
      example, the "Universal Declaration on Bioethics and Human Rights" sponsored by
      the United Nations Educational, Scientific, and Cultural Organization seeks to
      promote ethical guidance on bioethical issues. From the vantage of philosophical
      ethics, it fails to rank or specify its stated principles, justify controversial
      principles, clarify key terms, or say what is meant by calling potentially
      conflicting norms "foundational." From the vantage of improving the public
      discourse about bioethical problems and seeking ethical solutions in the public
      arena, however, this document may have an important role. The goals and relations
      between bioethics as a second-order discipline and public discourse are explored.

PMID- 19387002
TI  - The UNESCO Declaration on Bioethics and Human Rights: a canon for the ages?
AB  - The UNESCO Universal Declaration on Bioethics and Human Rights of 2005 purports
      to articulate universal norms for bioethics. However, this document has met with
      mixed reviews. Some deny that the elaboration of universal bioethics norms is
      needed; some deny that UNESCO has the expertise or authority to articulate such
      norms; some regard the content of the UNESCO document as too vague or general to
      be useful; and some regard the document as a cog in the effort of like-minded
      cosmopolitans to codify their particular moral intuitions in international law.
      This issue examines the potential merits and pitfalls of the Universal
      Declaration on Bioethics and Human Rights.

PMID- 19387003
TI  - Inattentive symptoms of ADHD are related to evening orientation.
AB  - OBJECTIVE: Morningness is a stable characteristic of individuals, related to
      impulsivity and novelty seeking. The evening orientation is a risk factor for
      psychiatric conditions such as depression and personality disorders. The authors
      hypothesized that adults suspected of having ADHD are more evening oriented than
      adults without ADHD. METHOD: Exploratory factor analyses were performed on the
      polychoric correlation matrices of the full Adult Self-Report Scale for ADHD
      (ASRS) and the Composite Scale of Morningness (CSM). RESULTS: As expected, two
      factors for the ASRS--Inattention and Impulsivity- Hyperactivity--and three
      factors for the CSM were retrieved. All three CSM factors correlated negatively
      with ASRS Inattention, none with ASRS Impulsivity-Hyperactivity. CONCLUSION:
      Inattention is more strongly related to eveningness than is Impulsivity
      Hyperactivity, and therefore eveningness may constitute an endophenotype of the
      predominantly inattentive subtype of ADHD. These findings need to be replicated
      in a patient population with a standardized assessment of sleep quality.

PMID- 19387004
TI  - Rescue of coagulation factor VII function by the U1+5A snRNA.
AB  - Our previous studies with genomic minigenes have demonstrated that an engineered
      small nuclear RNA-U1 (U1+5a) partially rescued coagulation factor VII (FVII) mRNA
      processing impaired by the 9726+5G>A mutation. Here, to evaluate the U1+5a
      effects on FVII function, we devised a full-length FVII splicing-competent
      construct (pSCFVII-wt). This construct drove in COS-1 cells the synthesis of
      properly processed FVII transcripts and of secreted functional FVII (23 +/- 4
      ng/mL), which were virtually undetectable upon introduction of the 9726+5G>A
      mutation (pSCFVII-9726+5a). Cotransfection of pSCFVII-9726+5a with pU1+5a
      resulted in a partial rescue of FVII splicing and protein biosynthesis. The level
      increase in medium was dose dependent and, with a molar excess (1.5x) of pU1+5a,
      reached 9.5% plus or minus 3.2% (5.0 +/- 2.8 ng/mL) of FVII-wt coagulant
      activity. These data provide the first insights into the U1-snRNA-mediated rescue
      of donor splice sites at protein level, thus further highlighting its therapeutic
      implications in bleeding disorders, which would benefit even from tiny increase
      of functional levels.

PMID- 19387005
TI  - Pesticide exposure and risk of monoclonal gammopathy of undetermined significance
      in the Agricultural Health Study.
AB  - Pesticides are associated with excess risk of multiple myeloma, albeit
      inconclusively. We included 678 men (30-94 years) from a well-characterized
      prospective cohort of restricted-use pesticide applicators to assess the risk of
      monoclonal gammopathy of undetermined significance (MGUS). Serum samples from all
      subjects were analyzed by electrophoresis performed on agarose gel; samples with
      a discrete or localized band were subjected to immunofixation. Age-adjusted
      prevalence estimates of MGUS were compared with MGUS prevalence in 9469 men from
      Minnesota. Associations between pesticide exposures and MGUS prevalence were
      assessed by logistic regression models adjusted for age and education level.
      Among study participants older than 50 years (n = 555), 38 were found to have
      MGUS, yielding a prevalence of 6.8% (95% CI, 5.0%-9.3%). Compared with men from
      Minnesota, the age-adjusted prevalence of MGUS was 1.9-fold (95% CI, 1.3- to 2.7
      fold) higher among male pesticide applicators. Among applicators, a 5.6-fold (95%
      CI, 1.9- to 16.6-fold), 3.9-fold (95% CI, 1.5- to 10.0-fold), and 2.4-fold (95%
      CI, 1.1- to 5.3-fold) increased risk of MGUS prevalence was observed among users
      of the chlorinated insecticide dieldrin, the fumigant mixture carbon
      tetrachloride/carbon disulfide, and the fungicide chlorothalonil, respectively.
      In summary, the prevalence of MGUS among pesticide applicators was twice that in
      a population-based sample of men from Minnesota, adding support to the hypothesis
      that specific pesticides are causatively linked to myelomagenesis.

PMID- 19387006
TI  - Two distinct pathways regulate platelet phosphatidylserine exposure and
      procoagulant function.
AB  - Procoagulant platelets exhibit hallmark features of apoptotic cells, including
      membrane blebbing, microvesiculation, and phosphatidylserine (PS) exposure.
      Although platelets possess many well-known apoptotic regulators, their role in
      regulating the procoagulant function of platelets is unclear. To clarify this, we
      investigated the consequence of removing the essential mediators of apoptosis,
      Bak and Bax, or directly inducing apoptosis with the BH3 mimetic compound ABT
      737. Treatment of platelets with ABT-737 triggered PS exposure and a marked
      increase in thrombin generation in vitro. This increase in procoagulant function
      was Bak/Bax- and caspase-dependent, but it was unaffected by inhibitors of
      platelet activation or by chelating extracellular calcium. In contrast, agonist
      induced platelet procoagulant function was unchanged in Bak(-/-)Bax(-/-) or
      caspase inhibitor-treated platelets, but it was completely eliminated by
      extracellular calcium chelators or inhibitors of platelet activation. These
      studies show the existence of 2 distinct pathways regulating the procoagulant
      function of platelets.

PMID- 19387007
TI  - Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic
      features of 9 cases.
AB  - In chronic lymphocytic leukemia (CLL), spontaneous regressions are an exceptional
      phenomenon, whose biologic features are unknown. We describe 9 CLL patients who
      underwent a spontaneous clinical regression over an 11-year follow-up, despite a
      residual neoplastic clone detected by flow cytometry. CD38 and ZAP-70 were
      negative in all cases. Immunoglobulin heavy chain variable region (IgVH) genes,
      mutated in all 7 evaluable patients, were restricted to the VH3 family in 6, with
      the usage of V(H)3-30 gene in 2. The light chain variable region genes were
      mutated in 6 of 8 cases, with the use of V(kappa)4-1 gene in 3. Microarray
      analysis of CLL cells showed a distinctive genomic profile with an
      overrepresentation of BCR-related and ribosomal genes, regulators of signal
      transduction and transcription. The number of activated T lymphocytes expressing
      IFN-gamma, TNF-alpha, and IL-4 was similar between CLL in spontaneous regression
      and healthy persons. In conclusion, spontaneous clinical regressions can occur in
      CLL despite the persistence of the neoplastic clone, and the biologic features
      include negative CD38 and ZAP-70, mutated V(H)3-30 and V(kappa)4-1 genes. The
      peculiar gene profile suggests that BCR signaling may play an important role in
      this scenario as the most significant feature of the leukemic clone in
      regression.

PMID- 19387008
TI  - Frequent CBL mutations associated with 11q acquired uniparental disomy in
      myeloproliferative neoplasms.
AB  - Recent evidence has demonstrated that acquired uniparental disomy (aUPD) is a
      novel mechanism by which pathogenetic mutations in cancer may be reduced to
      homozygosity. To help identify novel mutations in myeloproliferative neoplasms
      (MPNs), we performed a genome-wide single nucleotide polymorphism (SNP) screen to
      identify aUPD in 58 patients with atypical chronic myeloid leukemia (aCML; n =
      30), JAK2 mutation-negative myelofibrosis (MF; n = 18), or JAK2 mutation-negative
      polycythemia vera (PV; n = 10). Stretches of homozygous, copy neutral SNP calls
      greater than 20Mb were seen in 10 (33%) aCML and 1 (6%) MF, but were absent in
      PV. In total, 7 different chromosomes were involved with 7q and 11q each affected
      in 10% of aCML cases. CBL mutations were identified in all 3 cases with 11q aUPD
      and analysis of 574 additional MPNs revealed a total of 27 CBL variants in 26
      patients with aCML, myelofibrosis or chronic myelomonocytic leukemia. Most
      variants were missense substitutions in the RING or linker domains that abrogated
      CBL ubiquitin ligase activity and conferred a proliferative advantage to 32D
      cells overexpressing FLT3. We conclude that acquired, transforming CBL mutations
      are a novel and widespread pathogenetic abnormality in morphologically related,
      clinically aggressive MPNs.

PMID- 19387010
TI  - Diversity in degrees of freedom of mitochondrial transit peptides.
AB  - Most mitochondrial proteins are synthesized in the cytosol of eukaryotic cells as
      precursor proteins carrying N-terminal extensions called transit peptides or
      presequences, which mediate their specific transport into mitochondria. However,
      plant cells possess a second potential target organelle for such transit
      peptides, the chloroplast. It can therefore be assumed that mitochondrial transit
      peptides in plants are exposed to an increased demand of specificity, which in
      turn leads to reduced degrees of freedom in these transit peptides compared with
      those of nonplant organisms. Our study investigates this hypothesis using fractal
      dimension. Statistical analysis of sequence data shows that the fractal dimension
      of mitochondrial transit peptides in plants is indeed significantly lower than
      that from nonplant organisms.

PMID- 19387011
TI  - Is interlineage recombination responsible for low divergence of mitochondrial
      nad3 genes in Mytilus galloprovincialis?
AB  - The existence of mtDNA recombination in animals has been confirmed by several
      case studies. Still, for Mytilus mussels possessing two divergent mitochondrial
      genomes (M and F), which can recombine, no recombination between coding sequences
      of highly diverged M and F genomes has been shown. Based on the full sequences of
      both genomes, it has been suggested that particularly low divergence observed
      within the mitochondrial nad3 gene of the Mytilus galloprovincialis mussel may be
      caused by its exceptionally low evolutionary rate. Here, we contribute a new pair
      of mitochondrial genomes typical for M. galloprovincialis and show that this low
      divergence is not a sign of evolutionary conservation but is rather caused by the
      acquisition of an F-related sequence by the published M genome of M.
      galloprovincialis. The most likely scenario for this apparent mtDNA-coding region
      recombination case is an assembly artifact.

PMID- 19387009
TI  - Dinoflagellate spliced leader RNA genes display a variety of sequences and
      genomic arrangements.
AB  - Spliced leader (SL) trans-splicing is a common mRNA processing mechanism in
      dinoflagellates, in which a 22-nt sequence is transferred from the 5'-end of a
      small noncoding RNA, the SL RNA, to the 5'-end of mRNA molecules. Although the SL
      RNA gene was shown initially to be organized as tandem repeats with transcripts
      of 50-60 nt, shorter than most of their counterparts in other organisms, other
      gene organizations and transcript lengths were reported subsequently. To address
      the evolutionary gradient of gene organization complexity, we thoroughly examined
      transcript and gene organization of the SL RNA in a phylogenetically and
      ecologically diverse group of dinoflagellates representing four Orders. All these
      dinoflagellates possessed SL RNA transcripts of 50-60 nt, although in one species
      additional transcripts of up to 92 nt were also detected. At the genomic level,
      various combinations of SL RNA and 5S rRNA tandem gene arrays, including SL RNA
      only, 5S rRNA-only, and mixed SL RNA-5S rRNA (SL-5S) clusters, were amplified by
      polymerase chain reaction for six dinoflagellates, containing intergenic spacers
      ranging from 88 bp to over 1.2 kb. Of these species, no SL-5S cluster was
      detected in Prorocentrum minimum, and only Karenia brevis showed the U6 small
      nuclear RNA gene associated with these mixed arrays. The 5S rRNA-only array was
      also found in three dinoflagellates, along with two SL-5S-adjacent arrangements
      found in two other species that could represent junctions. Two species contained
      multimeric SL exon repeats with no associated intron. These results suggest that
      1) both the SL RNA tandem repeat and the SL-5S cluster genomic organizations are
      an "ancient" and widespread feature within the phylum of dinoflagellates and 2)
      rampant genomic duplication and recombination are ongoing independently in each
      dinoflagellate lineage, giving rise to the highly complex and diversified genomic
      arrangements of the SL RNA gene, while conserving the length and structure of the
      functional SL RNA.

PMID- 19387012
TI  - Rapid evolution of immune proteins in social insects.
AB  - The existence of behavioral traits connected to defense against pathogens
      manifests the importance of pathogens in the evolution of social insects.
      However, very little is known about how pathogen pressure has affected the
      molecular evolution of genes involved in their innate immune system. We have
      studied the sequence evolution of several immune genes in ants and honeybees. The
      results show high rates of evolution in both ants and honeybees as measured by
      the ratio of amino acid changes to silent nucleotide changes, the ratio being
      clearly higher than in Drosophila immune genes or in nonimmunity genes of bees.
      This conforms to our expectations based on high pathogen pressure in social
      insects. The codon-based likelihood method found clear evidence of positive
      selection only in one ant gene, even though positive selection has earlier been
      found in both ant and termite immune genes. There is now indication that
      selection on the amino acid composition of the immune-related genes has been an
      important part in the fight against pathogens by social insects. However, we
      cannot distinguish in all the cases whether the high observed d(N)/d(S) ratio
      results from positive selection within a restricted part of the studied genes or
      from relaxation of purifying selection associated with effective measures of
      behaviorally based colony-level defenses.

PMID- 19387013
TI  - Discrete shoot and root stem cell-promoting WUS/WOX5 functions are an
      evolutionary innovation of angiosperms.
AB  - The morphologically diverse bodies of seed plants comprising gymnosperms and
      angiosperms, which separated some 350 Ma, grow by the activity of meristems
      containing stem cell niches. In the dicot model Arabidopsis thaliana, these are
      maintained by the stem cell-promoting functions of WUS and WUSCHEL-related
      homeobox 5 (WOX5) in the shoot and the root, respectively. Both genes are members
      of the WOX gene family, which has a monophyletic origin in green algae. The
      establishment of the WOX gene phylogeny from basal land plants through
      gymnosperms to basal and higher angiosperms reveals three major branches: a basal
      clade consisting of WOX13-related genes present in some green algae and
      throughout all land plant genomes, a second clade containing WOX8/9/11/12
      homologues, and a modern clade restricted to seed plants. The analysis of the
      origin of the modern branch in two basal angiosperms (Amborella trichopoda and
      Nymphaea jamesoniana) and three gymnosperms (Pinus sylvestris, Ginkgo biloba, and
      Gnetum gnemon) shows that all members of the modern clade consistently found in
      monocots and dicots exist at the base of the angiosperm lineage, including WUS
      and WOX5 orthologues. In contrast, our analyses identify a single WUS/WOX5
      homologue in all three gymnosperm genomes, consistent with a monophyletic origin
      in the last common ancestor of gymnosperms and angiosperms. Phylogenetic data,
      WUS- and WOX5-specific evolutionary signatures, as well as the expression pattern
      and stem cell-promoting function of the single gymnosperm WUS/WOX5 pro-orthologue
      in Arabidopsis indicate a gene duplication event followed by subfunctionalization
      at the base of angiosperms.

PMID- 19387014
TI  - Images in clinical medicine. Bilateral subacute subdural hematomas.

PMID- 19387015
TI  - Association of HTRA1 mutations and familial ischemic cerebral small-vessel
      disease.
AB  - BACKGROUND: The genetic cause of cerebral autosomal recessive arteriopathy with
      subcortical infarcts and leukoencephalopathy (CARASIL), which is characterized by
      ischemic, nonhypertensive, cerebral small-vessel disease with associated alopecia
      and spondylosis, is unclear. METHODS: In five families with CARASIL, we carried
      out linkage analysis, fine mapping of the region implicated in the disease, and
      sequence analysis of a candidate gene. We also conducted functional analysis of
      wild-type and mutant gene products and measured the signaling by members of the
      transforming growth factor beta (TGF-beta) family and gene and protein expression
      in the small arteries in the cerebrum of two patients with CARASIL. RESULTS: We
      found linkage of the disease to the 2.4-Mb region on chromosome 10q, which
      contains the HtrA serine protease 1 (HTRA1) gene. HTRA1 is a serine protease that
      represses signaling by TGF-beta family members. Sequence analysis revealed two
      nonsense mutations and two missense mutations in HTRA1. The missense mutations
      and one of the nonsense mutations resulted in protein products that had
      comparatively low levels of protease activity and did not repress signaling by
      the TGF-beta family. The other nonsense mutation resulted in the loss of HTRA1
      protein by nonsense-mediated decay of messenger RNA. Immunohistochemical analysis
      of the cerebral small arteries in affected persons showed increased expression of
      the extra domain-A region of fibronectin and versican in the thickened tunica
      intima and of TGF-beta1 in the tunica media. CONCLUSIONS: CARASIL is associated
      with mutations in the HTRA1 gene. Our findings indicate a link between repressed
      inhibition of signaling by the TGF-beta family and ischemic cerebral small-vessel
      disease, alopecia, and spondylosis.

PMID- 19387016
TI  - Changes in the incidence and duration of periods without insurance.
AB  - BACKGROUND: Policymakers have recently proposed ways of providing health care
      coverage for an increased number of uninsured persons. However, there are few
      data that show how the incidence and duration of periods in which persons do not
      have insurance have changed over time. METHODS: We used two data sets from the
      Survey of Income and Program Participation of the U.S. Census Bureau: one that
      covered the period from 1983 through 1986 (25,946 persons), and another that
      covered the period from 2001 through 2004 (40,282 persons). For each set of
      years, we estimated the probability that a person would be uninsured for some
      period of time and the probability that a person would subsequently obtain
      private or public insurance. We also estimated the probabilities that persons in
      various demographic groups would become uninsured over the course of a year and
      would remain uninsured for various amounts of time. RESULTS: The percentage of
      the population that lost insurance in a 12-month period increased from 19.8% in
      1983-1986 to 21.8% in 2001-2004 (P=0.04). The percentage that was uninsured for a
      period of time increased markedly among persons with the lowest educational level
      and predominantly represented loss of private coverage. The percentage of new
      uninsured periods that ended within 24 months increased from 73.8% to 79.7%
      between the two study periods (P<0.001); increases were seen in all age groups
      and among persons of all educational levels. Transition from no insurance to
      private insurance decreased from 65.2% to 59.2% (P<0.001). Transition from no
      insurance to public insurance increased from 8.7% to 20.4% (P<0.001).
      CONCLUSIONS: As compared with the years from 1983 through 1986, from 2001 through
      2004, more people, particularly those with the lowest educational level, had
      periods in which they were not insured. The periods without insurance were
      shorter in 2001-2004 than they were in 1983-1986, since an increase in
      transitions to public coverage offset a reduction in transitions to private
      coverage. Our results portend difficulties if private coverage continues to
      decline and is not offset by further expansions of public insurance.

PMID- 19387017
TI  - Minimally invasive total knee arthroplasty for osteoarthritis.

PMID- 19387018
TI  - Images in clinical medicine. Pulmonary arteriovenous fistula.

PMID- 19387019
TI  - Case records of the Massachusetts General Hospital. Case 13-2009. A 54-year-old
      woman with respiratory failure and a cavitary lesion in the lung.

PMID- 19387020
TI  - Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia.

PMID- 19387021
TI  - Vitiligo.

PMID- 19387022
TI  - More on reports of esophageal cancer with oral bisphosphonate use.

PMID- 19387023
TI  - Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy.

PMID- 19387024
TI  - Thomas L. Petty Aspen Lung Conference: Asthma: Insights and Expectations.
      Introduction and perspective.

PMID- 19387026
TI  - Eosinophilic and neutrophilic inflammation in asthma: insights from clinical
      studies.
AB  - Cellular inflammation of the airways with eosinophils and neutrophils is a
      characteristic feature of asthma and is considered relevant to the pathogenesis
      of the disease. Studies of large numbers of subjects with well-characterized
      asthma in recent years has resulted in new insights about the clinical and
      pathologic correlates of eosinophilic and neutrophilic inflammation in asthma.
      For example, eosinophilic asthma is a distinct phenotype of asthma that is
      associated pathologically by thickening of the basement membrane zone and
      pharmacologically by corticosteroid responsiveness. In contrast, noneosinophilic
      asthma, a sizeable subgroup of asthma that includes patients with severe disease,
      is not characterized by thickening of the basement membrane zone, and it appears
      to be relatively corticosteroid resistant. Eosinophilic and neutrophilic asthma
      are not mutually exclusive subtypes of asthma. Rather, neutrophils accumulate in
      the airways in patients with asthma with more severe airflow obstruction, where
      eosinophils may also be present in excess. In addition, neutrophils are prominent
      in airway secretions during acute severe asthma exacerbations, where it is
      possible that they have roles in both the initiation and resolution of attacks.
      These insights about the relationships between cellular inflammation and disease
      phenotypes of asthma support the concept that different subgroups of patients
      with asthma, despite clinically similar features, can be defined by specific
      cellular and molecular markers. The promise now is that these markers will
      ultimately guide personalized treatment programs.

PMID- 19387025
TI  - Nuclear factor kappaB, airway epithelium, and asthma: avenues for redox control.
AB  - A wealth of recent studies points to the importance of airway epithelial cells in
      the orchestration of inflammatory responses in the allergic inflamed lung.
      Studies also point to a role of oxidative stress in the pathophysiology of
      chronic inflammatory diseases. This article provides a perspective on the
      significance of airway epithelial cells in allergic inflammation, and reviews the
      relevance of the transcription factor, nuclear factor kappaB, herein. We also
      provide the reader with a perspective on the role that oxidants can play in lung
      homeostasis, and address the concept of "redox biology." In addition, we review
      recent evidence that highlights potential inhibitory roles of oxidants on nuclear
      factor kappaB activation and inflammation, and discuss recent assays that have
      become available to probe the functional roles of oxidants in lung biology.

PMID- 19387027
TI  - Innate immunity and asthma.
AB  - Asthma remains a major health problem worldwide that has increased in developed
      countries. Much of the focus in asthma research in the past has been on adaptive,
      antigen-dependent immune responses. Recent work suggests that the innate, non
      antigen-dependent immune system plays a critical role in asthma pathogenesis.
      Here we will highlight innate receptors and cells in the context of allergic
      responses. Reviewing animal models and human studies, we focus on interactions of
      innate and adaptive immunity.

PMID- 19387028
TI  - Bugs and asthma: a different disease?
AB  - The prevalence of asthma has dramatically increased in recent decades.
      Exacerbations of asthma are a large contributor to asthma-related costs, and are
      primarily caused by viral and atypical bacterial infections. Rhinoviruses (RVs)
      are the most common viruses detected after an asthma exacerbation. RVs,
      respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) viral
      infections early in life can induce wheezing and are associated with the
      development of asthma later in life. Atypical bacterial infections from
      Mycoplasma pneumoniae and Chlamydia pneumoniae have also been linked to chronic
      asthma and potential asthma exacerbations. In this article, we will discuss
      recent developments in viral infections, specifically RV, RSV, and hMPV, and
      atypical bacterial infections as causes of asthma exacerbations, including new
      data focusing on the host immune response in airway epithelial cells and animal
      models of infection.

PMID- 19387029
TI  - The origins of asthma and chronic obstructive pulmonary disease in early life.
AB  - Results from birth cohort and cross-sectional studies of young children with
      wheezing have uncovered strong associations between both lung function and immune
      responses in early life and the subsequent development of persistent wheezing and
      chronic airway obstruction up to mid-adulthood. It is now apparent that the
      pattern of bronchial hyperresponsiveness, deficits in lung function, and
      structural airway remodeling that are characteristic of asthma may be already
      established during the preschool years in most patients. Interactions between
      acute viral infections, especially those due to rhinovirus and respiratory
      syncytial virus, and exposure to perennial aeroallergens may induce persistent
      alterations in immune responses and airway function in susceptible subjects.
      Similarly, deficits in airway function present shortly after birth predict
      airflow limitation in early adult life, which in turn is a strong predisposing
      factor for chronic obstructive pulmonary disease. The fact that these alterations
      are more likely to occur during early life and even in utero than later during
      childhood suggests that there a developmental window of susceptibility during
      which exposures can disrupt normal growth trajectories. Novel strategies for
      primary prevention of chronic respiratory diseases will be based on the
      identification of the genetic and environmental factors that interactively cause
      these disruptions.

PMID- 19387031
TI  - Genetics of asthma: where are we and where do we go?
AB  - Since the recognition that asthma is genetically determined, enormous progress
      has been made to understand which genes determine disease development in
      interaction with each other and/or with different environmental factors. This is
      the result of rapid developments in techniques for genotyping and statistical
      analyses. However, we are only at the beginning of understanding the complex
      nature of asthma. Follow-up of both clinical and environmental measures in a
      standardized way in numerous prospective cohorts is needed to establish which
      sets of genes and environmental factors determine the different phenotypes of
      asthma. This includes differences between sex, asthma severity, asthma remission,
      and asthma progression. Investigation of genetic profiling and gene expression
      profiling may further help to better understand the underlying pathophysiologic
      mechanisms, taking into account the insight in the biology currently present.
      Only by collaborative efforts of many groups of researchers that join forces in
      DNA analyses will it be possible to help to develop preventive strategies for
      asthma.

PMID- 19387030
TI  - Pediatric asthma: a different disease.
AB  - Asthma currently affects the lives of more than 30 million Americans from infancy
      to the elderly. In many ways, pediatric asthma differs from adult asthma,
      including childhood-onset adult asthma. Despite many advances in our
      understanding of the disease, the natural history of asthma is not well defined,
      especially in different subsets of patients. For many with allergic asthma the
      disease has its origins in early childhood, associated with early sensitization
      to aeroallergens and exposure to repeated viral infections. These early life
      exposures, coupled with genetically determined susceptibility, have a major
      impact on the natural history of the disease. A number of risk factors during the
      critical early stages in the initiation of asthma have been associated with
      subsequent outcomes. In addition, protective factors linked to early life
      experiences have also been delineated which may impact the development of atopy
      and asthma and reduce the prevalence of these diseases. Cumulatively, the data
      highlight the critical nature of this early period in which immune/inflammatory
      responses in the lung are initiated and serve to maintain the disease in
      subsequent years.

PMID- 19387032
TI  - Epithelium, inflammation, and immunity in the upper airways of humans: studies in
      chronic rhinosinusitis.
AB  - The purpose of this review is to discuss recent findings made during studies of
      the upper airways and sinuses of people with chronic rhinosinusitis (CRS) in the
      context of the literature. CRS is a chronic inflammatory disorder affecting
      nearly 30 million Americans and is generally resistant to therapy with
      antibiotics and glucocorticoids (Meltzer EO and coworkers, J Allergy Clin Immunol
      2004;114:155-212). We have formed a collaboration that consists of
      otolaryngologists, allergists, and basic scientists to address the underlying
      immunologic and inflammatory processes that are occurring in, and possibly
      responsible for, this disease. The main emphasis of our work has been to focus on
      the roles that epithelium, in the sinuses and upper airways, plays as both a
      mediator and regulator of immune and inflammatory responses. It is not our
      intention here to provide a comprehensive review of the literature in this area,
      but we will try to put our work in the context of the findings of others (Kato A
      and Schleimer RP, Curr Opin Immunol 2007;19:711-720; Schleimer RP and coworkers,
      J Allergy Clin Immunol 2007;120:1279-1284). In particular, we discuss the
      evidence that epithelial cell responses are altered in CRS, including those
      relevant to regulation of dendritic cells, T cells, B cells, and barrier
      function.

PMID- 19387033
TI  - Disrupting actin-myosin-actin connectivity in airway smooth muscle as a treatment
      for asthma?
AB  - Breathing is known to functionally antagonize bronchoconstriction caused by
      airway muscle contraction. During breathing, tidal lung inflation generates force
      fluctuations that are transmitted to the contracted airway muscle. In vitro,
      experimental application of force fluctuations to contracted airway smooth muscle
      strips causes them to relengthen. Such force fluctuation-induced relengthening
      (FFIR) likely represents the mechanism by which breathing antagonizes
      bronchoconstriction. Thus, understanding the mechanisms that regulate FFIR of
      contracted airway muscle could suggest novel therapeutic interventions to
      increase FFIR, and so to enhance the beneficial effects of breathing in
      suppressing bronchoconstriction. Here we propose that the connectivity between
      actin filaments in contracting airway myocytes is a key determinant of FFIR, and
      suggest that disrupting actin-myosin-actin connectivity by interfering with actin
      polymerization or with myosin polymerization merits further evaluation as a
      potential novel approach for preventing prolonged bronchoconstriction in asthma.

PMID- 19387034
TI  - Remodeling in asthma.
AB  - Airway remodeling refers to the structural changes that occur in both the large
      and the small airways of miscellaneous diseases, including asthma. In asthma,
      airway structural changes include subepithelial fibrosis, increased smooth muscle
      mass, enlargement of glands, neovascularization, and epithelial alterations.
      Although controversial, airway remodeling is commonly attributed to the
      underlying chronic inflammatory process. These remodeling changes contribute to
      thickening of airway walls and consequently lead to airway narrowing, bronchial
      hyperresponsiveness, airway edema, and mucous hypersecretion. Airway remodeling
      is associated with poorer clinical outcome among patients with asthma. Early
      diagnosis and prevention of airway remodeling has the potential to decrease
      disease severity, to improve control, and to prevent disease expression. In this
      article, we briefly provide an update on the characteristic features of airway
      remodeling observed in asthma and their clinical consequences.

PMID- 19387035
TI  - Physiologic dysfunction of the asthmatic lung: what's going on down there,
      anyway?
AB  - Asthma is a syndrome of lung dysfunction characterized by airflow obstruction,
      reversibility to bronchodilators, and airways hyperresponsiveness (AHR). There is
      a growing body of evidence that suggests that the principle defect in asthma is
      the occlusion of the airway lumen by liquid, fibrin, and mucus. The fall in
      FEV(1) observed in asthma is best explained by a loss of communicating airspaces
      and the rise in residual lung volume. Imaging studies in both human patients and
      experimental animals support this hypothesis. An increased propensity for the
      airways to close can be a cause of AHR. We conclude that loss of lung volume
      plays a central role in determining the dysfunction of the asthmatic lung as
      measured by FEV(1). Together, these recent findings provide a better
      understanding of the causes of airflow obstruction and AHR, suggesting new
      avenues for the development of more effective asthma therapies.

PMID- 19387036
TI  - Asthma therapies revisited: what have we learned?
AB  - Asthma is a heterogenous disorder related to numerous biologic, immunologic, and
      physiologic components that generate multiple clinical phenotypes. Further,
      genetic and environmental factors interact in ways that produce variability in
      both disease onset and severity and differential expression based on both the age
      and sex of the patient. Thus, the natural history of asthma is complex in terms
      of disease expression, remission, relapse, and progression. As such, therapy for
      asthma is complicated and has been approached from the standpoints of primary,
      secondary, and tertiary prevention. Presently, asthma cannot be cured but can be
      controlled in most patients, an indication that most of the success clinical
      research strategies have realized has been in the area of tertiary prevention.
      Since for many adult patients with asthma their disease had its roots in early
      life, much recent research has focused on events during early childhood that can
      be linked to subsequent asthma development with the hopes of creating appropriate
      interventions to alter its natural history of expression. These research
      approaches can be categorized into three questions. Who is the right patient to
      treat? When is the right time to begin treatment? And finally, what is the
      appropriate treatment to prescribe?

PMID- 19387037
TI  - Thomas L. Petty Aspen Lung Conference: Asthma: Insights and Expectations.
      Conference summary.

PMID- 19387066
TI  - Intrastromal keratotomy with femtosecond laser avoids profibrotic TGF-beta1
      induction.
AB  - PURPOSE: To examine expression of the profibrotic cytokine TGF-beta1 after
      selective intrastromal corneal injury with the use of a femtosecond laser.
      METHODS: Rabbits underwent monocular intrastromal keratotomy at a preoperatively
      determined corneal depth of 160 to 200 mum with the use of a femtosecond laser.
      Femtosecond laser-induced TGF-beta1 expression was compared in nonoperated
      control eyes and eyes treated with photorefractive keratectomy (PRK). Follow-up
      examinations were performed 1, 3, 7, and 28 days after surgery. TGF-beta1 protein
      was identified by immunofluorescence labeling. With the use of laser-capture
      microdissection, epithelial, stromal, and endothelial cell layers were collected,
      and changes in TGF-beta1 mRNA expression were quantified with quantitative RT
      PCR. RESULTS: TGF-beta1 mRNA and protein expression did not significantly
      increase after intrastromal femtosecond laser keratotomy. In contrast, TGF-beta1
      was induced in corneal epithelial and stromal cells after PRK and showed up to 23
      fold higher TGF-beta1 mRNA levels compared with control corneas. The increase of
      TGF-beta1 mRNA levels after PRK was accompanied by increased TGF-beta1 protein
      production. CONCLUSIONS: Isolated stromal injury with a femtosecond laser does
      not result in induction of the profibrotic cytokine TGF-beta1. Because TGF-beta1
      has been implicated in a fibrotic response of the corneal stroma to injury,
      absence of TGF-beta1 induction argues for a favorable wound-healing response.
      These findings support highly selective intrastromal procedures in refractive
      surgery.

PMID- 19387067
TI  - Stromal edema in klf4 conditional null mouse cornea is associated with altered
      collagen fibril organization and reduced proteoglycans.
AB  - PURPOSE: Klf4, one of the highly expressed transcription factors in the mouse
      cornea, plays an important role in maturation and maintenance of the ocular
      surface. In this study, the structure and proteoglycan composition of the Klf4
      conditional null (Klf4CN) corneal stroma was investigated, to further
      characterize the previously reported Klf4CN stromal edema. METHODS: Collagen
      fibril spacing and diameter were calculated from scattering intensity profiles
      from small angle synchrotron x-ray scattering patterns obtained across the cornea
      along a vertical meridian at 0.5-mm intervals. Collagen fibril organization and
      proteoglycans were visualized by electron microscopy (EM), with or without the
      cationic dye cuprolinic blue. Proteoglycans and glycosaminoglycans were further
      analyzed by fluorophore-assisted carbohydrate electrophoresis (FACE) and
      immunoblot analysis. Q-RT-PCR was used to measure the transcript levels. RESULTS:
      In the central cornea, the average collagen interfibrillar Bragg spacing
      increased from 44.5 nm (SD +/-1.8) in wild-type to 66.5 nm (SD +/-2.3) in Klf4CN,
      as measured by x-ray scattering and confirmed by EM. Mean collagen fibril
      diameter increased from 32 nm (SD +/-0.4) in wild-type to 42.3 nm (SD +/-4.8) in
      Klf4CN corneal stroma. Downregulation of proteoglycans detected by EM in the
      Klf4CN stroma was confirmed by FACE and immunoblot analysis. Q-RT-PCR showed
      that, whereas the Klf4CN corneal proteoglycan transcript levels remained
      unchanged, matrix metalloproteinase (MMP) transcript levels were significantly
      upregulated. CONCLUSIONS: The Klf4CN corneal stromal edema is characterized by
      increased collagen interfibrillar spacing and increased diameter of individual
      fibrils. The stroma also exhibits reduced interfibrillar proteoglycans
      throughout, which is possibly caused by increased expression of MMPs.

PMID- 19387068
TI  - Age-related changes in the spatial distribution of human lens alpha-crystallin
      products by MALDI imaging mass spectrometry.
AB  - PURPOSE: To develop a protocol for MALDI (matrix-assisted laser desorption
      ionization) imaging mass spectrometry for mapping the distributions of alpha
      crystallin and its modified forms in human lens tissue as a function of lens age
      and cataract. METHODS: Frozen human lenses were cryosectioned equatorially and
      axially into 20-mum-thick sections, and the sections were mounted onto conductive
      glass slides by methanol soft-landing. An ethanol washing procedure facilitated
      uniform matrix crystal formation by a two-step matrix deposition procedure to
      produce high-quality mass spectral data. Molecular images of modified and
      unmodified alpha-crystallin subunits were obtained from mass spectral data
      acquired in 100-mum steps across normal and cataractous lens sections. Proteins
      extracted from the lens sections were digested with endoproteinase Glu-C and
      subjected to mass spectrometric analysis for identification of modifications.
      RESULTS: Intact alpha-crystallin signals were detected primarily in the outer
      cortical fiber cells in lenses up to 29 years of age. Multiple truncation
      products were observed for alpha-crystallin that increased in abundance, both
      with distance into the lens and with lens age. Phosphorylated alphaB-crystallin
      forms were most abundant in the cortical region of older lenses. In axial
      sections, no significant anterior-posterior pole variation was observed. A
      previously unreported alphaA-crystallin mutation was detected in an age-matched
      cataractous human lens. CONCLUSIONS: A method has been developed to spatially map
      the age-related changes of human lens alpha-crystallin by MALDI imaging mass
      spectrometry including a novel L52F alphaA-crystallin mutation in a cataractous
      lens. Application of this spatially resolved proteomic technique to lens biology
      enhances the understanding of alpha-crystallin protein processing in aging and
      diseased human lenses.

PMID- 19387069
TI  - Minor influence of myopic laser in situ keratomileusis on the posterior corneal
      surface.
AB  - PURPOSE: To check whether myopic LASIK induces changes on the posterior corneal
      surface. METHODS: A Scheimpflug system (Pentacam; Oculus, GmbH, Wetzlar, Germany)
      was used to measure preoperative and postoperative posterior corneal topography
      in 27 eyes (of 14 subjects) that had undergone standard myopic LASIK surgery
      (attempted corrections between -1.25 and -8.50 D) and on 18 nonoperated eyes (9
      subjects). A hybrid porcine-plastic eye model was developed to validate the
      measurement technique. Longitudinal displacement of the posterior corneal apex
      and changes of the apical radius of curvature and asphericity were computed.
      RESULTS: Measurements on a hybrid model eye of known posterior corneal geometry
      showed that the measured posterior corneal radius of curvature was minimally
      affected by the geometry of the anterior surface. The measurements on patients
      showed that, on average, the only relevant (though clinically unimportant) change
      in radius of curvature and asphericity occurred the first day after surgery
      (DeltaR = -28 +/- 34 microm and DeltaQ = -0.06 +/- 0.06). No statistically
      significant change was observed afterward. The change in radius was more
      pronounced in the vertical direction than in the horizontal direction. On
      average, there was no significant displacement of the posterior corneal apex.
      Individual changes over time did not show a systematic trend across patients, and
      control subjects experienced changes of the same order of magnitude. CONCLUSIONS:
      The Pentacam Scheimpflug system can be used reliably to assess changes in the
      posterior corneal radius of curvature after LASIK. There is no evidence of
      surgically induced changes in the corneal posterior surface beyond 1 week after
      surgery.

PMID- 19387071
TI  - Causes of blindness and visual impairment in Nigeria: the Nigeria national
      blindness and visual impairment survey.
AB  - PURPOSE: Determine causes of blindness and visual impairment among adults aged
      >or=40 years. METHODS: Multistage, stratified, cluster random sampling with
      probability proportional to size procedures were used to identify a nationally
      representative sample of 15,027 persons >or=40 years of age. Distance vision was
      measured with a reduced logMAR tumbling E-chart. Clinical examination included a
      basic eye examination of all subjects and a more detailed examination of those
      who had presenting vision <6/12 in either eye. Cause for vision loss was assigned
      to all subjects with presenting vision <6/12 in any eye. RESULTS: Of the 15,122
      persons aged >or=40 years who were enumerated, 13,599 (89.9%) were examined. In
      84%, blindness was avoidable. Uncorrected refractive errors were responsible for
      57.1% of moderate (<6/18-6/60) visual impairment. Cataract (43%) was the
      commonest cause of blindness (<3/60). Prevalence of cataract-related blindness
      was 1.8% (95% CI: 1.57-2.05) and glaucoma-related blindness was 0.7% (95% CI:
      0.55-0.88). Increasing age was associated with increasing prevalence of all major
      blinding conditions. Females, illiterate persons, and residents in the North East
      geopolitical zone had significantly higher odds of cataract-induced blindness and
      severe visual impairment. CONCLUSIONS: The high proportion of avoidable
      blindness, with half being attributable to cataract alone and uncorrected
      refractive errors being responsible for 57% of moderate visual impairment, means
      that appropriate and accessible refraction and surgical services need to be
      provided. If priority attention is not given, the number of blind and severely
      visually impaired adults in Nigeria will increase by >40% over the next decade.

PMID- 19387070
TI  - Inhibition of human scleral fibroblast cell attachment to collagen type I by
      TGFBIp.
AB  - PURPOSE: Transforming growth factor beta-induced protein (TGFBIp; 68 kDa) is a
      secreted extracellular matrix (ECM) protein that has been demonstrated to
      regulate cell attachment in a variety of cell types. The sclera synthesizes and
      secretes TGFBIp, which may function to facilitate scleral ECM remodeling events
      associated with myopia development. Here the authors report that human scleral
      fibroblasts (HSFs) express TGFBI and that its protein product, TGFBIp, mediates
      an effect on cell attachment. METHODS: TGFBI/TGFBIp expression was evaluated by
      RT-PCR and immunoblot of HSF lysates and culture supernatants. The effect of
      rTGFBIp (50 microg/mL) on cell attachment to collagen type I was determined with
      the use of fluid-phase cell attachment assays in HSFs, human foreskin fibroblasts
      (HFFs), and human corneal stroma fibroblasts (HCFs). Binding assays using
      biotinylated rTGFBIp were used to assess TGFBIp binding to the HSF surface. Flow
      cytometry and immunocytochemistry were used to determine both alphavbeta3 and
      alphavbeta5 expression and localization to the HSF cell surface. RESULTS: HSFs
      expressed TGFBI and secreted TGFBIp (approximately 833 ng/h). rTGFBIp
      significantly decreased (25 microg/mL; P <or= 0.05) HSF attachment to collagen
      type I, whereas rTGFBIp did not significantly affect cell attachment of HFFs (P =
      0.50) or HCFs (P = 0.24) to collagen compared with BSA. Integrins alphavbeta3 and
      alphavbeta5 were detected on the cell surface, and both anti-alphavbeta3 and anti
      alphavbeta5 functionally blocked rTGFBIp binding to HSFs. CONCLUSIONS: TGFBIp
      plays an inhibitory role in HSF attachment to collagen type I in vitro through
      interactions with alphavbeta3 and alphavbeta5 integrin receptors. These results
      suggest that TGFBIp may modulate scleral cell-matrix interactions in vivo,
      thereby affecting scleral viscoelasticity.

PMID- 19387072
TI  - The effects of transient retinal detachment on cavity size and glial and neural
      remodeling in a mouse model of X-linked retinoschisis.
AB  - PURPOSE: To determine the cellular consequences of retinal detachment in
      retinoschisin knockout (Rs1-KO) mice, a model for retinoschisin in humans.
      METHODS: Experimental retinal detachments (RDs) were induced in the right eyes of
      both Rs1-KO and wild-type (wt) control mice. Immunocytochemistry was performed on
      retinal tissue at 1, 7, or 28 days after RD with antibodies to anti-GFAP, 
      neurofilament, and -rod opsin to examine cellular changes after detachment.
      Images of the immunostained tissue were captured by laser scanning confocal
      microscopy. Quantitative analysis was performed to measure the number of Hoechst
      stained photoreceptor nuclei and their density, number, and size of inner retinal
      cavities, as well as the number of subretinal glial scars. RESULTS: Since
      detachments were created with balanced salt solution, by examination, all retinas
      had spontaneously reattached by 1 day. Cellular responses common to many
      photoreceptor degenerations occurred in the nondetached retinas of Rs1-KO mice,
      and, of importance, RD did not appear to significantly accentuate these
      responses. The number of schisis cavities was not changed after detachment, but
      their size was reduced. CONCLUSIONS: These data indicate that large short-term RD
      in Rs1-KO mice, followed by a period of reattachment may cause a slight increase
      in photoreceptor cell death, but detachments do not accentuate the gliosis and
      neurite sprouting already present and may in fact reduce the size of existing
      retinal cavities. This finding suggests that performing subretinal injections to
      deliver therapeutic agents may be a viable option in the treatment of patients
      with retinoschisis without causing significant cellular damage to the retina.

PMID- 19387073
TI  - A novel antimicrobial peptidoglycan recognition protein in the cornea.
AB  - PURPOSE: In an earlier gene expression study, the authors identified a novel
      antimicrobial gene, Peptidoglycan recognition protein 1 (Pglyrp1), in the mouse
      cornea. Here the expression of the Pglyrp1 transcript and the encoded protein,
      PGLYRP1, in the cornea was investigated. The role of PGLYRP1 in the cornea was
      further investigated using wild-type and Pglyrp1-deficient mice. This is the
      first report of this antimicrobial protein in the cornea. METHODS: PGLYRP1 was
      detected in the cornea and was further localized to the epithelium by
      immunohistology, confocal microscopy, immunoblotting, and real-time PCR. The role
      of PGLYRP1 in the cornea was investigated by comparing the response of wild-type
      and Pglyrp1(-/-) mice to corneal epithelial wounds and Pseudomonas aeruginosa
      mediated corneal infections. The antibacterial effects of corneal PGLYRP1 were
      assayed by measuring bacterial growth in vitro, in the presence of wild-type
      corneal epithelial extracts, before and after antibody-mediated blocking of
      PGLYRP1. RESULTS: PGLYRP1 is expressed at high levels in the mouse corneal
      epithelium. PGLYRP1 was localized to the mouse corneal epithelium and the human
      corneal epithelium. The Pglyrp1(-/-) mouse shows delayed healing and poor
      clearing of bacterial keratitis; in vitro its epithelial protein extract shows
      reduced bacteriostatic activity compared with wild-type mice. CONCLUSIONS:
      PGLYRP1 is a novel antimicrobial protein of the corneal epithelium and protects
      the ocular surface from bacterial infections.

PMID- 19387074
TI  - Effects of elevated Pax6 expression and genetic background on mouse eye
      development.
AB  - PURPOSE: To analyze the effects of Pax6 overexpression and its interaction with
      genetic background on eye development. METHODS: Histologic features of eyes from
      hemizygous PAX77(+/-) transgenic (high Pax6 gene dose) and wild-type mice were
      compared on different genetic backgrounds. Experimental PAX77(+/-)<-->wild-type
      and control wild-type<-->wild-type chimeras were analyzed to investigate the
      causes of abnormal eye development in PAX77(+/-) mice. RESULTS: PAX77(+/-) mice
      showed an overlapping but distinct spectrum of eye abnormalities to Pax6(+/-)
      heterozygotes (low Pax6 dose). Some previously reported PAX77(+/-) eye
      abnormalities did not occur on all three genetic backgrounds examined. Several
      types of eye abnormalities occurred in the experimental PAX77(+/-)<-->wild-type
      chimeras, and they occurred more frequently in chimeras with higher contributions
      of PAX77(+/-) cells. Groups of RPE cells intruded into the optic nerve sheath,
      indicating that the boundary between the retina and optic nerve may be displaced.
      Both PAX77(+/-) and wild-type cells were involved in this ingression and in
      retinal folds, suggesting that neither effect was cell-autonomous. Cell
      autonomous effects included failure of PAX77(+/-) and wild-type cells to mix
      normally and overrepresentation of PAX77(+/-) in the lens epithelium and RPE.
      CONCLUSIONS: The extent of PAX77(+/-) eye abnormalities depended on PAX77(+/-)
      genotype, genetic background, and stochastic variation. Chimera analysis
      identified two types of cell-autonomous effects of the PAX77(+/-) genotype.
      Abnormal cell mixing between PAX77(+/-) and wild-type cells suggests altered
      expression of cell surface adhesion molecules. Some phenotypic differences
      between PAX77(+/-)<-->wild-type and Pax6(+/-)<-->wild-type chimeras may reflect
      differences in the levels of PAX77(+/-) and Pax6(+/-) contributions to chimeric
      lenses.

PMID- 19387075
TI  - Efficiency and safety of AAV-mediated gene delivery of the human ND4 complex I
      subunit in the mouse visual system.
AB  - PURPOSE: To evaluate the efficiency and safety of AAV-mediated gene delivery of a
      normal human ND4 complex I subunit in the mouse visual system. METHODS: A nuclear
      encoded human ND4 subunit fused to the ATPc mitochondrial targeting sequence and
      FLAG epitope were packaged in AAV2 capsids that were injected into the right eyes
      of mice. AAV-GFP was injected into the left eyes. One month later, pattern
      electroretinography (PERG), rate of ATP synthesis, gene expression, and
      incorporation of the human ND4 subunit into the murine complex I were evaluated.
      Quantitative analysis of ND4FLAG-injected eyes was assessed compared with green
      fluorescent protein (GFP)-injected eyes. RESULTS: Rates of ATP synthesis and PERG
      amplitudes were similar in ND4FLAG- and GFP-inoculated eyes. PERG latency was
      shorter in eyes that received ND4FLAG. Immunoprecipitated murine complex I gave
      the expected 52-kDa band of processed human ND4FLAG. Confocal microscopy revealed
      perinuclear expression of FLAG colocalized with mitochondria-specific fluorescent
      dye. Transmission electron microscopy revealed FLAG immunogold within
      mitochondria. Compared with Thy1.2-positive retinal ganglion cells (RGCs),
      quantification was 38% for FLAG-positive RGCs and 65% for GFP-positive RGCs.
      Thy1.2 positive-RGC counts in AAV-ND4FLAG were similar to counts in control eyes
      injected with AAV-GFP. CONCLUSIONS: Human ND4 was properly processed and imported
      into the mitochondria of RGCs and axons of mouse optic nerve after intravitreal
      injection. Although it had approximately two-thirds the efficiency of GFP, the
      expression of normal human ND4 in murine mitochondria did not induce the loss of
      RGCs, ATP synthesis, or PERG amplitude, suggesting that allotopic ND4 may be safe
      for the treatment of patients with Leber hereditary optic neuropathy.

PMID- 19387076
TI  - An FMRI study of word-level recognition and processing in patients with age
      related macular degeneration.
AB  - PURPOSE: To compare the cortical networks that underlie word recognition and
      processing in patients with age-related macular degeneration (AMD) with those of
      normally sighted control subjects using functional magnetic resonance imaging
      (fMRI). METHODS: Six patients with bilateral geographic atrophy who were using an
      eccentrically located preferred retinal location were recruited. Six younger and
      six older control subjects were also recruited. Patients and control subjects
      were asked to perform a three-letter (3Let) and a six-letter (6Let) word
      recognition task during fMRI on a 3.0-Tesla MRI scanner. The fMRI tasks were two
      condition, blocked-design paradigms in which central fixation was alternated with
      a word recognition task requiring a forced, two-choice reaction time
      living/nonliving judgment. RESULTS: When contrasted with controls, patients
      showed increased brain activation in a widespread cortical network that included
      regions identified as the frontal eye fields, both superior and inferior parietal
      lobules, and regions within the prefrontal cortex. Peak activation within these
      prefrontal regions was correlated with increased accuracy (r = 0.875, P = 0.024;
      r = 0.848, P = 0.033) and decreased reaction times (r = -0.861, P = 0.028; r = 
      0.842, P = 0.036) for the 3Let task within the group of patients. Correlations
      between peak activity and behavioral performance were also found in both the
      right (-0.818, P = 0.047) and left (r = -0.839, P = 0.037) superior parietal
      lobules for the 3Let task. Similar relationships were found for the 6Let task.
      CONCLUSIONS: Patients with AMD demonstrate increased prefrontal and parietal
      activation compared with controls. The authors posit that these increases reflect
      increased top-down involvement in basic word recognition to compensate for
      decreased sensory function.

PMID- 19387077
TI  - Transient retinal effects of 5,6-dimethylxanthenone-4-acetic acid (DMXAA,
      ASA404), an antitumor vascular-disrupting agent in phase I clinical trials.
AB  - PURPOSE: 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), an anticancer vascular
      disrupting agent, has induced transient visual symptoms in some patients.
      Exploratory investigations were undertaken to characterize the visual
      disturbances in two consecutive phase I trials. METHODS: Assessments were made in
      21 patients before and immediately after a 20-minute IV infusion of DMXAA,
      including visual acuity, funduscopy, color discrimination, pattern
      electroretinography (PERG), pattern visual-evoked potentials (VEP), and full
      field electroretinography (ERG). Evaluation of late effects was undertaken
      subsequently in 12 patients before and after 6 weeks of IV DMXAA at one dose per
      week. RESULTS: Frequency and intensity of transient visual disturbance increased
      with DMXAA dose, occurring in two thirds of patients at 3000 mg x m(-2). Symptoms
      included blurring, flickering, fragmentation, alteration of colors, and contrast
      and mild photosensitivity, starting during the infusion and resolving completely,
      usually within 60 minutes. Visual acuity was unchanged but color discrimination
      was perturbed. Dose-dependent increases in PERG P50 implicit time by up to 23 ms
      returned toward baseline values within 90 minutes. Prominent transient changes on
      ERG included prolonged scotopic rod and 30-Hz flicker implicit times and reduced
      30-Hz flicker amplitude. In the second trial, no clinically significant sustained
      effects were detected, although an increase in bright flash a-wave implicit time
      (P = 0.022) was seen on whole-group analysis. In vitro studies showed nonspecific
      phosphodiesterase inhibition by DMXAA. CONCLUSIONS: DMXAA induced acute,
      transient disturbance of retinal activity consistent with phosphodiesterase
      inhibition. No clinically significant cumulative effects were noted and most
      effects occurred at doses higher than those used in ongoing clinical trials
      (ClinicalTrials.gov numbers, NCT00856336, NCT00863733, and NCT00003697).

PMID- 19387078
TI  - Lipofuscin and autofluorescence metrics in progressive STGD.
AB  - PURPOSE: To evaluate Stargardt disease (STGD) progression and relative lipofuscin
      levels via autofluorescence image analysis. METHODS: The relationship between
      focally increased autofluorescence (FIAF), geographic atrophy (GA) and focally
      decreased autofluorescence (FDAF) was analyzed in serial, registered
      autofluorescence (AF) scans of 10 patients with STGD (20 eyes, 40 scans; mean
      follow-up, 2.0 years) using automated techniques. RESULTS: GA progressed
      uniformly in a transition zone with minimal FIAF. Only 4.3% of FIAF progressed to
      GA or FDAF, despite significant progression of GA (median 30%/year) and FDAF
      (mean, 29%/year). As a spatial predictor, the mean chance of FIAF for progression
      to FDAF was 4.3% +/- 4.4%, significantly less than that of random areas (6.7% +/-
      4.0%, P = 0.029, Mann-Whitney test). In the seven eyes with GA, the mean chance
      of FIAF in the transition zone for transition to GA was 12% +/- 8.9%,
      significantly less than that of random areas (33% +/- 3.6%, P = 0.026, Mann
      Whitney test). CONCLUSIONS: Autofluorescent flecks and FIAF deposits with AF
      levels elevated above the initial macular background were less likely in the
      short term (2 years) to transform to GA and FDAF (AF levels below the final
      background) than random areas, suggesting additional mechanisms beyond direct
      lipofuscin toxicity. FIAF/FDAF levels were observed to fluctuate, with focal
      remodeling of FIAF and FDAF, or rarely, even transition of FDAF to FIAF. FDAF
      tended to develop, not coincident with, but adjacent to initial FIAF. Because AF
      identifies these characteristic biological markers so specifically,
      autofluorescence metrics merit consideration in the study of STGD.

PMID- 19387079
TI  - Molecular sequelae of histone deacetylase inhibition in human retinoblastoma cell
      lines: clinical implications.
AB  - PURPOSE: To characterize the molecular sequelae induced in retinoblastoma (Rb)
      cells by histone deacetylase inhibitors (HDACIs). Hydroxamic acid-based HDACIs
      such as vorinostat (suberoylanilide hydroxamic acid) induce the differentiation
      and apoptosis of transformed cells. Vorinostat has demonstrated significant
      anticancer activity against hematologic and solid tumors at doses well tolerated
      by patients and has been approved for the treatment of patients with cutaneous T
      cell lymphoma. METHODS: The authors evaluated the effects of the HDACIs
      vorinostat and m-carboxycinnamic acid bis-hydroxamide on the Rb cell lines Y79
      and WERI-Rb1 with the use of the MTT assay, BrdU incorporation assay, flow
      cytometry, immunoblotting, gene-expression profiling, quantitative RT-PCR, and NF
      kappaB DNA-binding assay. RESULTS: Both HDACIs were effective against both Rb
      cell lines, inducing growth arrest and apoptosis in vitro. Vorinostat increased
      p53 expression and activated caspases -8, -9 and -3, whereas caspase inhibition
      abrogated vorinostat-induced apoptosis. Vorinostat downregulated baseline NF
      kappaB activity and potentiated the activity of the DNA-damaging chemotherapeutic
      doxorubicin. Gene expression profiling and qRT-PCR demonstrated that vorinostat
      modulated the mRNA levels of genes important for signal transduction, cell cycle,
      cellular metabolism, stress response, apoptosis, extracellular matrix synthesis,
      and cell differentiation. Notably, several transcripts involved in the ephrin and
      Notch signaling pathways were upregulated. CONCLUSIONS: HDACIs, such as
      vorinostat, induce caspase-dependent apoptosis in Rb cells, downregulate baseline
      NF-kappaB activity, and potentiate the effectiveness of conventional
      chemotherapy. The finding that vorinostat augments the effectiveness of
      doxorubicin provides a rationale for future clinical studies looking at the use
      of vorinostat in combination with conventional chemotherapy in Rb.

PMID- 19387080
TI  - Enhancement on primate corneal endothelial cell survival in vitro by a ROCK
      inhibitor.
AB  - PURPOSE: The transplantation of cultivated corneal endothelial cells (CECs) has
      gained attention recently for the treatment of patients with corneal endothelial
      dysfunction. However, an efficient culturing technique for human (H)CECs has yet
      to be properly established. The present study was conducted to investigate the
      applicability of the Rho kinase (ROCK) inhibitor Y-27632 in promoting cultivation
      of cynomolgus monkey (M)CECs. METHODS: MCECs of cynomolgus monkeys were cultured
      in a medium containing 10 microM Y-27632. The number of viable cells adherent to
      culture plates were monitored by a luminescent cell-viability assay and colony
      growth was detected by toluidine blue staining. Proliferating cells were detected
      by Ki67 expression using flow cytometry and a BrdU-labeling assay for
      immunocytochemistry. Annexin V-positive apoptotic cells were analyzed by flow
      cytometry. RESULTS: The number of viable cultivated MCECs was enhanced by Y-27632
      addition after 24 hours in culture. The colony area of the culture in the
      presence of Y-27632 was higher than in the absence of Y-27632 on day 10. In Y
      27632-treated cultures, the number of Ki67-positive cells was significantly
      increased at 24 and 48 hours, and the number of proliferating BrdU-positive cells
      was increased at 48 hours. The number of Annexin V-positive apoptotic cells was
      decreased at 24 hours. CONCLUSIONS: The inhibition of Rho/ROCK signaling by
      specific ROCK inhibitor Y-27632 promoted the adhesion of MCECs, inhibited
      apoptosis, and increased the number of proliferating cells. These results suggest
      that the ROCK inhibitor may serve as a new tool for cultivating HCECs for
      transplantation.

PMID- 19387081
TI  - COL1A1 and COL2A1 genes and myopia susceptibility: evidence of association and
      suggestive linkage to the COL2A1 locus.
AB  - PURPOSE: Collagen involvement in myopia development via scleral remodeling is
      well-known. Recently, COL1A1 and COL2A1 gene polymorphisms were reported to be
      associated with high-grade and common myopia, respectively. This study was
      conducted to investigate whether these collagen genes are associated and/or
      genetically linked with myopia in large Caucasian family datasets. METHODS: High
      grade myopia was defined as <or=-5.00 D. Two independent datasets comprising 146
      (Duke) and 130 (Cardiff) families with high-grade myopia participated in the
      association study. Allelic discrimination assays were performed on tagging SNPs
      for COL1A1 and COL2A1. The pedigree disequilibrium test (PDT) and the association
      test in the presence of linkage (APL) were used for association analyses. Linkage
      analyses for COL2A1 locus markers were performed with the Fastlink and Merlin
      programs in conjunction with data obtained from our collaborative whole-genome
      linkage study (254 families). RESULTS: Significant association was identified
      between five SNPs (rs1034762, rs1635529, rs1793933, rs3803183, and rs17122571) of
      the COL2A1 locus and high-grade myopia (P < 0.045, minimum (min) P = 0.008) and
      with myopia status set at <or=-0.50 or -0.75 D (min P = 0.004) in the Duke
      dataset. The SNP rs1635529 also showed significant association in the Cardiff
      dataset (<or=-5.00 D, min P = 0.004; <or=-0.50 D, min P = 0.007). Linkage
      analyses showed suggestive linkage to the COL2A1 locus on 12q. No association was
      found between COL1A1 SNPs and any degree of myopia. CONCLUSIONS: The COL2A1 gene
      was associated with high-grade myopia in two independent Caucasian family
      datasets. COL1A1 gene polymorphisms were not associated with myopia in our
      dataset, indicating possible heterogeneity across different ethnicities.

PMID- 19387083
TI  - Lamina cribrosa and peripapillary sclera histomorphometry in normal and advanced
      glaucomatous Chinese eyes with various axial length.
AB  - PURPOSE: To measure laminar and peripapillary scleral architecture in normal and
      glaucomatous Chinese eyes with normal and those with elongated axial length.
      METHODS: The histomorphometric investigation included a normal group (nonaxially
      elongated eyes) of 40 human globes (40 patients; mean age, 41.3 +/- 13.4 years;
      range,15-68) enucleated because of malignant choroidal melanoma, a glaucomatous
      group (non-axially elongated eyes) of 55 eyes (55 patients; age, 43.3 +/- 20.3
      years; range, 12-88) enucleated because of painful secondary angle-closure
      glaucoma, and a group of 26 glaucomatous globes (glaucomatous elongated axial
      length group; 26 patients; age, 29.0 +/- 14.4 years; range, 12-60) with an axial
      length > 27.5 mm. Anterior-posterior histologic sections were morphometrically
      evaluated. RESULTS: The lamina cribrosa was significantly (P < 0.001) thicker in
      the normal group than in the glaucomatous group, in which it was significantly (P
      < 0.001) thicker than in the glaucomatous elongated-length group. Lamina cribrosa
      thickness decreased significantly with increasing axial length (P < 0.001) and
      presence of glaucoma (P < 0.001). Peripapillary scleral thickness close to the
      optic nerve scleral canal and just outside of the optic nerve meninges decreased
      significantly with increasing axial length (P = 0.04 and P = 0.02, respectively).
      Peripapillary scleral thickness did not vary significantly between the
      glaucomatous group and the normal group. The distance between the intraocular
      space and cerebrospinal fluid space was (P < 0.001) shorter in the two
      glaucomatous groups than in the normal group. CONCLUSIONS: Lamina cribrosa
      thickness and peripapillary sclera thickness decreased significantly with axial
      length, in addition to a glaucoma-related thinning of the lamina cribrosa. In non
      axially elongated eyes, the peripapillary sclera thickness did not vary
      significantly between glaucomatous eyes and normal eyes.

PMID- 19387082
TI  - Embryonic corneal Schwann cells express some Schwann cell marker mRNAs, but no
      mature Schwann cell marker proteins.
AB  - PURPOSE: Embryonic chick nerves encircle the cornea in pericorneal tissue until
      embryonic day (E)9, then penetrate the anterior corneal stroma, invade the
      epithelium, and branch over the corneal surface through E20. Adult corneal
      nerves, cut during transplantation or LASIK, never fully regenerate. Schwann
      cells (SCs) protect nerve fibers and augment nerve repair. This study evaluates
      SC differentiation in embryonic chick corneas. METHODS: Fertile chicken eggs were
      incubated from E0 at 38 degrees C, 45% humidity. Dissected permeabilized corneas
      plus pericorneal tissue were immunostained for SC marker proteins. Other corneas
      were paraffin embedded, sectioned, and processed by in situ hybridization for
      corneal-, nerve-related, and SC marker gene expression. E9 to E20 corneas,
      dissected from pericorneal tissue, were assessed by real-time PCR (QPCR) for mRNA
      expression. RESULTS: QPCR revealed unchanging low to moderate SLIT2/ROBO and
      NTN/UNC5 family, BACE1, and CADM3/CADM4 expressions, but high NEO1 expression.
      EGR2 and POU3F1 expressions never surpassed PAX3 expression. ITGNA6/ITGNB4
      expressions increased 20-fold; ITGNB1 expression was high. SC marker S100 and MBP
      expressions increased; MAG, GFAP, and SCMP expressions were very low. Antibodies
      against the MPZ, MAG, S100, and SCMP proteins immunostained along pericorneal
      nerves, but not along corneal nerves. In the cornea, SLIT2 and SOX10 mRNAs were
      expressed in anterior stroma and epithelium, whereas PAX3, S100, MBP, and MPZL1
      mRNAs were expressed only in corneal epithelium. CONCLUSIONS: Embryonic chick
      corneas contain SCs, as defined by SOX10 and PAX3 transcription, which remain
      immature, at least in part because of stromal transcriptional and epithelial
      translational regulation of some SC marker gene expression.

PMID- 19387084
TI  - Infiltrating cells and IFNgamma production in the injected eye after uniocular
      anterior chamber inoculation of HSV-1.
AB  - PURPOSE: After uniocular anterior chamber (AC) inoculation with HSV-1, the
      anterior segment of the injected eye becomes inflamed and infected; however,
      virus does not spread from the anterior segment and infect the retina of the
      injected eye. The purpose of this study was to identify early infiltrating cells
      and to determine whether infiltrating cells produce interferon (IFN)gamma.
      METHODS: Euthymic, female, BALB/c mice were injected in one AC with 3 x 10(4) PFU
      of HSV-1 (KOS) in a volume of 2 microL. Mice from each group were killed at 12,
      24, 36, 48, and 72 hours post injection (pi), the eyes were enucleated, and
      frozen sections were stained with antibodies specific for IFNgamma, Mac-1
      (CD11b), CD49b, F4/80, CD4, CD8, and CD11c. The same antibodies were also used to
      stain single-cell suspensions of ocular cells for flow cytometry. RESULTS: In the
      anterior segment of the injected eye, the ciliary body, and iris were virus
      infected and inflamed, and infiltrating cells increased throughout the period of
      observation. Mac-1(+), CD49b(+), and F4/80(+) cells colocalized with IFNgamma in
      the anterior segment as early as 12 hours pi, and the percentage of Mac-1(+)
      cells increased in the injected eye beginning at 24 hours pi and continued to 72
      hours pi. CONCLUSIONS: Taken together, these results demonstrate that Mac-1(+)
      cells are important IFNgamma-producing cells in the injected eye before day 3 and
      suggest that the IFNgamma produced by these cells is involved in inhibition of
      anterior to posterior spread of virus in the injected eye.

PMID- 19387086
TI  - Dimethylarsinic acid in drinking water changed the morphology of urinary bladder
      but not the expression of DNA repair genes of bladder transitional epithelium in
      F344 rats.
AB  - Inorganic arsenic increases urinary bladder transitional cell carcinoma in
      humans. In F344 rats, dimethylarsinic acid (DMA[V]) increases transitional cell
      carcinoma. Arsenic-induced inhibition of DNA repair has been reported in cultured
      cell lines and in lymphocytes of arsenic-exposed humans, but it has not been
      studied in urinary bladder. Should inhibition of DNA damage repair in
      transitional epithelium occur, it may contribute to carcinogenesis or
      cocarcinogenesis. We investigated morphology and expression of DNA repair genes
      in F344 rat transitional cells following up to 100 ppm DMA(V) in drinking water
      for four weeks. Mitochondria were very sensitive to DMA(V), and swollen
      mitochondria appeared to be the main source of vacuoles in the transitional
      epithelium. Real-time reverse transcriptase polymerase chain reaction (Real-Time
      RT PCR) showed the mRNA levels of tested DNA repair genes, ataxia telangectasia
      mutant (ATM), X-ray repair cross-complementing group 1 (XRCC1), excision repair
      cross-complementing group 3/xeroderma pigmentosum B (ERCC3/XPB), and DNA
      polymerase beta (Polbeta), were not altered by DMA(V). These data suggested that
      either DMA(V) does not affect DNA repair in the bladder or DMA(V) affects DNA
      repair without affecting baseline mRNA levels of repair genes. The possibility
      remains that DMA(V) may lower damage-induced increases in repair gene expression
      or cause post-translational modification of repair enzymes.

PMID- 19387087
TI  - Spontaneous hibernomas in Sprague-Dawley rats.
AB  - Hibernomas are rare neoplasms originating in brown adipose tissue of humans and
      other animal species, including laboratory animals. Background incidence values
      for these tumors in all common strains of laboratory rats are generally accepted
      as being <0.1%. Between April 2000 and April 2007, however, sixty-two hibernomas
      (an overall prevalence of 3.52%) were observed in a total of 1760 Sprague-Dawley
      rats assigned to three carcinogenesis bioassays at two separate research
      laboratories. All rats were obtained from Charles River's breeding facilities in
      either Portage, Michigan, or Raleigh, North Carolina. Tumors (twenty-nine benign
      and thirty-three malignant) were randomly distributed among test article-treated
      and control groups and were considered to be spontaneous. Most tumors originated
      in the thoracic cavity, and they were usually described as soft, mottled to tan
      masses with nodular to lobulated profiles. Immunohistochemical procedures for
      uncoupling protein 1 (UCP1) confirmed brown adipose tissue as the site of origin
      rather than white fat. The marked increase in hibernomas in our studies suggests
      that greater numbers of spontaneous hibernomas may be sporadically encountered in
      future carcinogenesis studies with Sprague-Dawley rats. The increased potential
      for hibernomas to arise as spontaneous neoplasms has important implications in
      studies involving peroxisome proliferators-activated receptor (PPAR) drugs,
      lipophilic environmental chemicals (e.g., polychlorinated biphenyls), and other
      molecules or physiologic processes (e.g., beta-adrenergic stimulation) that may
      target brown fat adipocytes.

PMID- 19387088
TI  - Thyroid histopathology assessments for the amphibian metamorphosis assay to
      detect thyroid-active substances.
AB  - In support of an Organization for Economic Cooperation and Development (OECD)
      Amphibian Metamorphosis Assay (AMA) Test Guideline for the detection of
      substances that interact with the hypothalamic-pituitary-thyroid axis, a document
      was developed that provides a standardized approach for evaluating the
      histology/histopathology of thyroid glands in metamorphosing Xenopus laevis
      tadpoles. Here, a consolidated description of histology evaluation practices,
      core diagnostic criteria and severity grading schemes for the AMA, an atlas of
      the normal architecture of amphibian thyroid glands over the course of
      metamorphosis, and the core diagnostic criteria with examples of severity grades
      is provided. Core diagnostic criteria include thyroid gland hypertrophy/atrophy,
      follicular cell hypertrophy, and follicular cell hyperplasia. The severity
      grading scheme is semiquantitative and employs a four-grade approach describing
      ranges of variation within assigned ordinal classes: not remarkable, mild,
      moderate, and severe. The purpose of this severity grading approach is to provide
      an efficient, semi-objective tool for comparing changes (compound-related
      effects) among animals, treatment groups, and studies. Proposed descriptions of
      lesions for scoring the four core criteria are also given.

PMID- 19387089
TI  - The influence of estrogen on hepatobiliary osteopontin (SPP1) expression in a
      female rodent model of alcoholic steatohepatitis.
AB  - Our recent studies suggest that higher neutrophil infiltration in females
      correlates with increased hepatobiliary expression of osteopontin (OPN) in
      alcoholic steatohepatitis (ASH). The objective of this study was to understand
      the role of alcohol in altering estrogen levels in females by examining the
      effect of ethanol (EtOH) on the estrous cycle and then investigate the potential
      relationship between estradiol (E2) and hepatobiliary OPN expression in a female
      rat ASH model. Ovariectomized (OVX) and E2-implanted OVX rats in the ASH group
      were evaluated for OPN mRNA and protein expression. Low doses of E2 resulted in
      significant down-regulation of OPN protein and mRNA as compared to the OVX group.
      However, with increasing doses of E2, there was up-regulation of both OPN mRNA
      and protein. Osteopontin was localized primarily to the biliary epithelium. Liver
      injury assessed by serum ALT and histopathology revealed a pattern similar to OPN
      expression. In all groups, hepatic neutrophilic infiltration correlated
      positively with OPN expression. Based on these data, we conclude that in our ASH
      model, low doses of E2 appear to be hepatoprotective, whereas the protective
      effect appears to diminish with increasing doses of E2, although additional cause
      and effect studies are needed for confirmation.

PMID- 19387091
TI  - Jewish laws, customs, and practice in labor, delivery, and postpartum care.
AB  - Many communities throughout the world, especially in the United States and
      Israel, contain large populations of religiously observant Jews. The purpose of
      this article is to provide a comprehensive, descriptive guide to specific laws,
      customs, and practices of traditionally, religious observant Jews for the
      culturally sensitive management of labor, delivery, and postpartum. Discussion
      includes intimacy issues between husband and wife, dietary laws, Sabbath
      observance, as well as practices concerning prayer, communication trends, modesty
      issues, and labor and birth customs. Health care professionals can tailor their
      practice by integrating their knowledge of specific cultures into their
      management plan.

PMID- 19387090
TI  - Clock is important for food and circadian regulation of macronutrient absorption
      in mice.
AB  - Clock genes respond to external stimuli and exhibit circadian rhythms. This study
      investigated the expression of clock genes in the small intestine and their
      contribution in the regulation of nutrient absorption by enterocytes. We examined
      expression of clock genes and macronutrient transport proteins in the small
      intestines of wild-type and Clock mutant (Clk(mt/mt)) mice with free or limited
      access to food. In addition, we studied absorption of macronutrients in these
      mice. Intestinal clock genes show circadian expression and respond to food
      entrainment in wild-type mice. Dominant negative Clock in Clk(mt/mt) mice
      disrupts circadian expression and food entrainment of clock genes. The absorption
      of lipids and monosaccharides was high in Clk(mt/mt) mice whereas peptide
      absorption was reduced. Molecular studies revealed that Clock regulates several
      transport proteins involved in nutrient absorption. Clock plays an important role
      in light and food entrainment of intestinal functions by regulating nutrient
      transport proteins. Disruptions in intestinal circadian activity may contribute
      to hyperlipidemia and hyperglycemia.

PMID- 19387092
TI  - Association of acculturation status with beliefs, barriers, and perceptions
      related to cardiovascular disease prevention among racial and ethnic minorities.
AB  - Acculturation has been correlated with traditional cardiovascular disease risk
      factors. The purpose of this study was to examine the association between
      acculturation and health beliefs, barriers, and perceptions related to
      cardiovascular disease prevention. Racial/ethnic minority participants in the
      Family Intervention Trial for Heart Health were included in this analysis. Less
      acculturated minorities were more likely to have health beliefs that may impede
      prevention, have greater perceived susceptibility to disease, and believe in an
      external locus of control. Evaluating acculturation in clinical practice may be
      an opportunity to promote awareness, healthy behaviors, and prevention among
      immigrants.

PMID- 19387094
TI  - Deep tissue injury from a bioengineering point of view.
AB  - The phrasing of the National Pressure Ulcer Advisory Panel's (NPUAP) definition
      of deep tissue injury (DTI) was based on case reports, clinical observations, and
      experience. Although etiological studies of DTI, primarily related to
      characterizing biomechanical factors affecting onset and progression, support and
      strengthen parts of the NPUAP's definition, some recent findings suggest a need
      to re-evaluate the wording and perhaps refine future definitions of DTI.
      Application of existing bioengineering research to underlying biological,
      physical, biomechanical, and biochemical mechanisms involved in the definition of
      DTI suggests the following: 1) changes in skin color - ie, deviation of the local
      skin color from the surroundings - may indicate a DTI might be present, but color
      is not useful for quantifying the severity of injury; 2) the pressure and/or
      shear definition is inaccurate because it creates an artificial distinction
      between pressure and shear, which are physically coupled, and because it ignores
      tensional loads; 3) palpating tissue firmness at the wound site provides limited
      assessment information because tissue firmness will depend on the point in time
      along the course of DTI development. Damaged tissues might appear stiffer than
      surrounding tissues if examined when muscle tissue is locally contracted due to
      local rigor mortis but at a later stage damage might manifest as tissues that are
      softer than their surroundings when digestive enzymes start decomposing necrotic
      tissues; 4) skin temperature changes near the DTI site may reflect inflammatory
      response, causing local heating, or ischemic perfusion, causing local cooling;
      and 5) rapid deterioration of DTI is likely occurring due to muscle tissue
      stiffening at the rigor mortis phase; stiffened tissues abnormally deform
      adjacent tissues and this effect is amplified if muscles are atrophied. The
      application of interdisciplinary research may help clinicians and researchers
      move from evolving jargons, staging systems, and injury definitions to valid and
      reliable clinical instruments, which will improve clinical practice.

PMID- 19387093
TI  - Assessing diabetes dietary goals and self-management based on in-depth interviews
      with Latino and Caucasian clients with type 2 diabetes.
AB  - Latino (n = 10) and Caucasian (n = 8) clients with type 2 diabetes receiving care
      at a community health clinic participated in individual in-depth interviews
      assessing diabetes dietary self-management goal behaviors. Themes from interviews
      were identified using content analysis, which revealed current and future goals,
      influencing factors, and motivators and barriers to dietary modification for
      diabetes management. Implications for practice include simplifying goal setting
      to those goals with the greatest potential clinical impact or the greatest
      significance to the patient, in a socially supportive environment. Results
      contribute to future survey development and understanding how to optimize
      diabetes education for these populations.

PMID- 19387095
TI  - Clinical experience with wound biofilm and management: a case series.
AB  - Biofilm is a relatively new concept in the fields of infectious disease, wound
      infection, and healing. Although scientific research and "noise" regarding wound
      biofilm is increasing, little is known about the presentation, diagnosis,
      potential implications, and management strategies regarding wound biofilms. A
      series of four clinical cases is utilized to demonstrate the existence of wound
      biofilm. All patients presented with or developed a film on the wound bed that
      appeared to be distinct from slough; wounds also were failing to progress.
      Although the slough in some of the wounds was easily removed with traditional
      debridement methods, removal of the film required physical disruption with a
      curette or dry gauze. All wounds eventually progressed to healing. Considering
      the biofilm concept and available preclinical research, it is evident from this
      small case series that the appearance of biofilm in wounds is quite different
      from slough and requires different management strategies for its control. The
      evolving biofilm paradigm could profoundly change approaches to wound management.
      Additional research is needed in this evolving aspect of wound management.

PMID- 19387096
TI  - Reducing pressure ulcer prevalence rates in the long-term acute care setting.
AB  - Information about pressure ulcer prevalence, prevention, and optimal management
      strategies in the long-term acute care hospital (LTACH) setting is sparse.
      Although care processes in other patient care settings have been reported to
      affect pressure ulcer prevalence rates, the effect of such programs in the LTACH
      is unknown. To reduce perceived above-average pressure ulcer prevalence rates and
      improve care processes, a 108-bed LTACH used a failure mode and effects analysis
      to identify and address high-priority areas for improvement. Areas in need of
      improvement included a lack of 1) wound care professionals, 2) methods to
      consistently document prevention and wound data, and 3) an interdisciplinary
      wound care team approach, as well as a faulty electronic medical record. While
      prevalence data were collected, policies and procedures based on several
      published guidelines were developed and incorporated into the pressure ulcer plan
      of care by the newly established wound care team. Improved assessment and
      documentation methods, enhanced staff education, revised electronic records,
      wound care product reviews, and a facility-wide commitment to improved care
      resulted in a reduction of facility-acquired pressure ulcer prevalence from 41%
      at baseline to an average of 4.2% during the following 12 months as well as fewer
      missing electronic record data (<1% of charts had missing data). These study
      results suggest that staff education, better documentation, and a dedicated wound
      care team improves care practices and reduces pressure ulcer prevalence in the
      LTACH. Studies to increase knowledge about the LTACH patient population and their
      unique needs and risk profiles are needed.

PMID- 19387097
TI  - Global climate change and wound care: case study of an off-season vibrio
      alginolyticus infection in a healthy man.
AB  - Vibrio alginolyticus is a halophilic Gram-negative bacterium normally present in
      seawater. Vibrios are not capable of cutaneous invasion through intact skin and
      their isolation from extraintestinal sites is uncommon. However, interruptions in
      skin integrity (cuts or abrasions) can allow these bacteria to cause complicated
      skin and soft tissues infections. This case study describes the clinical
      assessment and management of a nonhealing traumatic wound, sustained in a coastal
      area during the winter months, in a healthy 70-year-old man. Culture results were
      positive for V. alginolyticus. Appropriate antibiotic treatment and topical wound
      care successfully resolved the infection. V. alginolyticus infections are usually
      benign; respond well to treatment, even with local therapy only; and tend to
      result from contact with warm ocean water. The clinical characteristics of the
      wound prompted a suspicion of a Vibrio infection even though the wound was
      sustained in the winter time and the patient did not have direct contact with
      ocean water. Although other case studies of Vibrio infections in the absence of
      direct contact with ocean water have been published, increased ocean temperatures
      due to global climate changes may explain the out-of-season infection in this
      patient. Clinicians should monitor the progression of wound healing and be
      prepared to modify treatment based on individual circumstances, especially in the
      case of unusual wound presentation, nonhealing, or a progressing wound infection.

PMID- 19387098
TI  - Skin cancers and wounds in the geriatric population: a review.
AB  - Diagnosis of wound malignancy often remains elusive and is of particular concern
      in the geriatric population because the average age for presentation of squamous
      cell cancer is 70 years. Basal and squamous cell carcinoma, as well as Marjolin's
      ulcer, may look like a chronic or acute wound, can develop in the wound itself,
      or be found in the scar tissue of these wounds. A complete patient history should
      include questions about sun exposure and personal and family history of skin
      cancer. Some wounds exhibit typical clinical signs of cancer - ie, raised
      borders, crusting - but many do not, making diagnosis more challenging. A punch,
      excisional, or ellipse biopsy from all ulcers and wounds that do not respond to
      appropriate protocols of care should be obtained. An accurate diagnosis is
      crucial to positive treatment outcomes.

PMID- 19387099
TI  - A micro-machined retro-reflector for improving light yield in ultra-high
      resolution gamma cameras.
AB  - High-resolution imaging of x-ray and gamma-ray distributions can be achieved with
      cameras that use charge coupled devices (CCDs) for detecting scintillation light
      flashes. The energy and interaction position of individual gamma photons can be
      determined by rapid processing of CCD images of individual flashes. Here we
      investigate the improvement of such a gamma camera when a micro-machined retro
      reflector is used to increase the light output of a continuous scintillation
      crystal. At 122 keV we found that retro-reflectors improve the intrinsic energy
      resolution (full width at half maximum (FWHM)) by 32% (from 50% to 34%) and the
      signal-to-noise (SNR) ratio by 18%. The spatial resolution (FWHM) was improved by
      about 4%, allowing us to obtain a resolution of 159 microm. The full width at
      tenth maximum (FWTM) improvement was 13%. Therefore, this enhancement is a next
      step towards realizing compact high-resolution devices for imaging gamma
      emitters.

PMID- 19387100
TI  - Dosimetry for the MRI accelerator: the impact of a magnetic field on the response
      of a Farmer NE2571 ionization chamber.
AB  - The UMC Utrecht is constructing a 1.5 T MRI scanner integrated with a linear
      accelerator (Lagendijk et al 2008 Radiother. Oncol. 86 25-9). The goal of this
      device is to facilitate soft-tissue contrast based image-guided radiotherapy, in
      order to escalate the dose to the tumour while sparing surrounding normal
      tissues. Dosimetry for the MRI accelerator has to be performed in the presence of
      a magnetic field. This paper investigates the feasibility of using a Farmer
      NE2571 ionization chamber for absolute dosimetry. The impact of the mcagnetic
      field on the response of this ionization chamber has been measured and simulated
      using GEANT4 Monte Carlo simulations. Two orientations of the ionization chamber
      with respect to the incident beam and the magnetic field which are feasible in
      the MRI accelerator configuration are taken into account. Measurements are
      performed using a laboratory magnet ranging from 0 to 1.2 T. In the simulations a
      range from 0 to 2 T is used. For both orientations, the measurements and
      simulations agreed within the uncertainty of the measurements and simulations. In
      conclusion, the response of the ionization chamber as a function of the magnetic
      field is understood and can be simulated using GEANT4 Monte Carlo simulations.

PMID- 19387101
TI  - Development of an imaging modality utilizing 2D optical signals during an EPI
      fluorescent optical mapping experiment.
AB  - Optical mapping is a commonly used technique to visualize the electrical activity
      in the heart. Recently, several groups have attempted to use the signals acquired
      in optical mapping to image the transmembrane potential in the heart, which would
      be particularly advantageous when studying the effects of defibrillation-type
      shocks throughout the wall of the heart. Our work presents an alternative imaging
      method that makes use of data obtained using multiple wavelengths and therefore
      multiple optical decay constants. A modified form of the diffusion equation
      Green's function for a semi-infinite slab of tissue is derived and used to relate
      the detected optical signals to the source of emission photons. Images using the
      optical signals are reconstructed using Gaussian quadrature and matrix inversion.
      Our results show that images can be obtained for source terms located below the
      tissue surface. Furthermore, we demonstrate that our reconstruction method's
      susceptibility to noise can be alleviated using sophisticated matrix inverse
      techniques, such as singular value decomposition. Sources that rapidly decay with
      depth or are highly localized in the image plane require more sophisticated
      techniques (e.g., regularization methods) to image the electrical activity in the
      heart. The work presented here demonstrates the feasibility of a new imaging
      technique of cardiac electrical activity using optical mapping.

PMID- 19387102
TI  - Exact image reconstruction with triple-source saddle-curve cone-beam scanning.
AB  - In this paper, we propose an exact shift-invariant filtered backprojection (FBP)
      algorithm for triple-source saddle-curve cone-beam CT. In this imaging geometry,
      the x-ray sources are symmetrically positioned along a circle, and the trajectory
      of each source is a saddle curve. Then, we extend Yang's formula from the single
      source case to the triple-source case. The saddle curves can be divided into four
      parts to yield four datasets. Each of them contains three data segments
      associated with different saddle curves, respectively. Images can be
      reconstructed on the planes orthogonal to the z-axis. Each plane intersects the
      trajectories at six points (or three points at the two ends) which can be used to
      define the filtering directions. Then, we discuss the properties of these curves
      and study the case of 2N+1 sources (N>or=2). A necessary condition and a
      sufficient condition are given to find efficient curves. Finally, we perform
      numerical simulations to demonstrate the feasibility of our triple-source saddle
      curve approach. The results show that the triple-source geometry is advantageous
      for high temporal resolution imaging, especially important for cardiac imaging
      and small animal imaging.

PMID- 19387104
TI  - Risk of incident Alzheimer's disease in diabetic patients: a systematic review of
      prospective trials.
AB  - Diabetes mellitus is an established risk factor of cognitive decline. This excess
      risk has frequently been attributed to cerebrovascular disease. The contribution
      of diabetes mellitus to the risk of Alzheimer's disease is less clear. We
      performed a systematic literature review based on prospective studies that
      examined the risk of incident Alzheimer's disease in diabetic patients. Fourteen
      studies in eleven different populations fulfilled the entry criteria. Only one
      study per population was included by pre-defined criteria, leaving eleven studies
      for analysis. All studies reported risk ratios greater than one (median 1.59,
      range 1.15-2.7). In four studies, this excess risk was statistically significant
      (median 1.73, range 1.59-1.9); in seven studies the lower border of the 95%
      confidence interval was below 1.0. Factors associated with significant results
      were a sample size of 600 or more diabetic subjects, inclusion of patients with
      mild glycemic dysregulation as assessed by oral glucose tolerance test, and a
      high proportion of diagnoses of Alzheimer's disease verified by autopsy or
      magnetic resonance imaging. Diabetes mellitus is likely to increase the risk of
      Alzheimer's disease. The association of Alzheimer's disease and diabetes mellitus
      is more clear-cut, if mild cases of diabetes mellitus are included in the
      analysis.

PMID- 19387103
TI  - The Alzheimer's disease-diabetes angle: inevitable fate of aging or metabolic
      imbalance limiting successful aging. Preface.

PMID- 19387105
TI  - Type II diabetes in mild cognitive impairment and Alzheimer's disease: results
      from a prospective population-based study in Germany.
AB  - Diabetes mellitus type 2 (T2DM) is considered to be an important risk factor for
      mild cognitive impairment (MCI) and subsequent Alzheimer's disease (AD). The
      majority of studies relating T2DM to MCI and AD were performed in North America.
      We investigated the potential impact of T2DM on the development of MCI and AD in
      the Interdisciplinary Longitudinal Study on Adult Development and Aging which
      involves a representative birth cohort of subjects born between 1930 and 1932 in
      Germany. Subjects received a thorough psycho-geriatric examination and
      neuropsychological testing; particular care was taken to exclude subjects with
      severe medical or neurological conditions sufficient to explain the cognitive
      deficits, or other major psychiatric disorders. When compared to healthy subjects
      (n=159), patients with MCI (n=108) or AD (n=26) showed a tendency towards
      increased prevalence rates for T2DM (17% vs. 23%; chi2=1.7, p=0.18). In both
      patients with MCI and controls, T2DM was associated with psychomotor slowing but
      not deficits in other cognitive domains typically involved in MCI. Our findings
      indicate that T2DM is involved in MCI and may aggravate the clinical picture as a
      concomitant factor.

PMID- 19387106
TI  - Adiposity, type 2 diabetes, and Alzheimer's disease.
AB  - This manuscript provides a comprehensive review of the epidemiologic evidence
      linking the continuum of adiposity and type 2 diabetes (T2D) with Alzheimer's
      disease (AD). The mechanisms relating adiposity and T2D to AD may include
      hyperinsulinemia, advanced products of glycosylation, cerebrovascular disease,
      and products of adipose tissue metabolism. Elevated adiposity in middle age is
      related to a higher risk of AD but the data on this association in old age is
      conflicting. Several studies have shown that hyperinsulinemia, a consequence of
      higher adiposity and insulin resistance, is also related to a higher risk of AD.
      Hyperinsulinemia is a risk factor for T2D, and numerous studies have shown a
      relation of T2D with higher AD risk. The implication of these associations is
      that a large proportion of the world population may be at increased risk of AD
      given the trends for increasing prevalence of overweight, obesity,
      hyperinsulinemia, and T2D. However these associations may present a unique
      opportunity for prevention and treatment of AD. Several studies in the prevention
      and treatment of T2D are currently conducting, or have planned, cognition
      ancillary studies. In addition, clinical trials using insulin sensitizers in the
      treatment or prevention of AD are under way.

PMID- 19387107
TI  - Mechanisms of ceramide-mediated neurodegeneration.
AB  - Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis
      (NASH) can be associated with cognitive impairment or early neurodegeneration.
      Previously, we showed that diet-induced obesity with T2DM and NASH results in
      mild neurodegeneration with some features of AD, including brain insulin
      resistance. In a companion study, we correlated obesity/T2DM/NASH-associated
      central nervous system (CNS) abnormalities with increased pro-ceramide gene
      expression in liver. Since ceramides are neurotoxic and cause insulin resistance,
      we directly investigated the role of ceramides as mediators of neurodegeneration
      using an in vitro culture model. We treated PNET2 human CNS neuronal cells with D
      erythro-Ceramide analogs (C2Cer:N-acetylsphinganine and C6Cer:N
      hexanoylsphinganine), or the inactive dihydroceramide analog (C2DCer) for 48 h,
      and probed for changes in genes and proteins that are critical to insulin/IGF
      signaling, and associated with neurodegeneration. Exposure to C6Cer>C2Cer
      impaired energy metabolism, viability, and insulin and insulin-like growth factor
      signaling mechanisms, and resulted in increased levels of AbetaPP-Abeta and pTau,
      whereas C2D had no significant effect on these parameters. CNS exposure to
      neurotoxic ceramides from exogenous sources, including liver, can cause
      neurodegeneration with impairments in insulin and IGF signaling mechanisms,
      similar to the findings in experimental models of obesity/T2DM, and NASH.

PMID- 19387108
TI  - Hepatic ceramide may mediate brain insulin resistance and neurodegeneration in
      type 2 diabetes and non-alcoholic steatohepatitis.
AB  - Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis
      (NASH) can be complicated by cognitive impairment and neurodegeneration.
      Experimentally, high fat diet (HFD)-induced obesity with T2DM causes mild
      neurodegeneration with brain insulin resistance. Since ceramides are neurotoxic,
      cause insulin resistance, and are increased in T2DM, we investigated the
      potential role of ceramides as mediators of neurodegeneration in the HFD
      obesity/T2DM model. We pair-fed C57BL/6 mice with a HFD or control diet for 4-20
      weeks and examined pro-ceramide gene expression in liver and brain and
      neurodegeneration in the temporal lobe. HFD feeding gradually increased body
      weight, but after 16 weeks, liver weight surged (P<0.001) due to lipid
      (triglyceride) accumulation (P<0.001), and brain weight declined (P<0.0001-Trend
      analysis). HFD feeding increased ceramide synthase, serine palmitoyl transferase,
      and sphingomyelinase expression in liver (P<0.05-P<0.001), but not brain. In HFD
      fed mice, temporal lobe levels of ubiquitin (P<0.001) and 4-hydroxynonenal
      (P<0.05 or P<0.01) increased, and tau, beta-actin, and choline acetyltransferase
      levels decreased (P<0.05-P<0.001) with development of NASH. In obesity, T2DM, or
      NASH, neurodegeneration with brain insulin resistance may be mediated by excess
      hepatic production of neurotoxic ceramides that readily cross the blood-brain
      barrier.

PMID- 19387110
TI  - An integrative view of the role of oxidative stress, mitochondria and insulin in
      Alzheimer's disease.
AB  - The processes underlying the pathogenesis of Alzheimer's disease involve several
      factors including impaired glucose/energy metabolism, mitochondrial dysfunction,
      oxidative stress and altered insulin-signaling pathways. This review is mainly
      devoted to discuss evidence supporting the notion that mitochondrial dysfunction
      and oxidative stress are interconnected and intimately associated with the
      development and progression of Alzheimer's disease. Furthermore, the review
      explores the role of insulin signaling in the pathophysiology of the disease.
      Indeed, several studies have begun to find links between insulin and mechanisms
      with clear pathogenic implications for this disorder. Understanding the key
      mechanisms involved in the etiopathogenesis of Alzheimer's disease may provide
      opportunities for the design of efficacious preventive and therapeutic
      strategies.

PMID- 19387109
TI  - Leptin: a novel therapeutic strategy for Alzheimer's disease.
AB  - Adipocyte-derived leptin appears to regulate a number of features defining
      Alzheimer's disease (AD) at the molecular and physiological level. Leptin has
      been shown to reduce the amount of extracellular amyloid beta, both in cell
      culture and animal models, as well as to reduce tau phosphorylation in neuronal
      cells. Importantly, chronic administration of leptin resulted in a significant
      improvement in the cognitive performance of transgenic animal models. In AD,
      weight loss often precedes the onset of dementia and the level of circulating
      leptin is inversely proportional to the severity of cognitive decline. It is
      speculated that a deficiency in leptin levels or function may contribute to
      systemic and CNS abnormalities leading to disease progression. Furthermore, a
      leptin deficiency may aggravate insulin-controlled pathways, known to be aberrant
      in AD. These observations suggest that a leptin replacement therapy may be
      beneficial for these patients.

PMID- 19387112
TI  - Reactive oxygen species in diabetes-induced vascular damage, stroke, and
      Alzheimer's disease.
AB  - A morphological hallmark of Alzheimer's disease (AD) is the deposition of amyloid
      beta peptide in plaques and along blood vessels. As several lines of evidence
      suggest that vascular dysfunction contributes to AD, the pathophysiology of
      diabetic vasculopathy and stroke may cast light on the vascular component of AD.
      In this review, we compile some recent findings on the role of reactive oxygen
      species in diabetes-induced vascular dysfunction and the consequent cerebral
      ischemia and compare them with key findings in AD. Overall, there is compelling
      evidence that reactive oxygen species play a key role in the pathophysiology of
      AD. Unfortunately, this insight has not yet led to a new treatment of AD.

PMID- 19387113
TI  - Common pathological processes and transcriptional pathways in Alzheimer's disease
      and type 2 diabetes.
AB  - Numerous epidemiological and experimental studies have established a strong
      connection between type 2 diabetes and the risk of the development of Alzheimer's
      disease. Indeed, several pathological features have been identified as common
      denominators of diabetic and Alzheimer's patients, including insulin resistance,
      dyslipidemia and inflammation, suggesting a close connection between the two
      disorders. Here we review common metabolic and inflammatory processes implicated
      in the pathogenesis of both disorders. In particular, the role of critical
      transcriptional checkpoints in the control of cellular metabolism, insulin
      sensitivity, and inflammation will be emphasized in this context. These
      transcriptional regulators hold great promise as new therapeutic targets in the
      potentially combined treatment of type 2 diabetes and Alzheimer's disease in the
      future.

PMID- 19387111
TI  - Oxidative stress in diabetes and Alzheimer's disease.
AB  - Oxidative stress plays a major role in diabetes as well as in Alzheimer's disease
      and other related neurological diseases. Intracellular oxidative stress arises
      due to the imbalance in the production of reactive oxygen/reactive nitrogen
      species and cellular antioxidant defense mechanisms. In turn, the excess reactive
      oxygen/reactive nitrogen species mediate the damage of proteins and nucleic
      acids, which have been shown to have direct and deleterious consequences in
      diabetes and Alzheimer's disease. Oxidative stress also contributes to the
      production of advanced glycation end products through glycoxidation and lipid
      peroxidation. The advanced glycation end products and lipid peroxidation products
      are ubiquitous to diabetes and Alzheimer's disease and serve as markers of
      disease progression in both disorders. Antioxidants and advanced glycation end
      products inhibitors, either induced endogenously or exogenously introduced, may
      counteract with the deleterious effects of the reactive oxygen/reactive nitrogen
      species and thereby, in prevention or treatment paradigms, attenuate or
      substantially delay the onset of these devastating pathologies.

PMID- 19387114
TI  - Inflammation and NF-kappaB in Alzheimer's disease and diabetes.
AB  - Inflammatory processes are a hallmark of many chronic diseases including
      Alzheimer's disease and diabetes mellitus. Fairly recent statistical evidence
      indicating that type 2 diabetes increases the risk of developing Alzheimer's
      disease has led to investigations of the potential common processes that could
      explain this relation. Here, we review the literature on how inflammation and the
      inducible nuclear factor NF-kappaB might be involved in both diabetes mellitus
      and Alzheimer's disease and whether these factors can link both diseases.

PMID- 19387115
TI  - Growth factors, AGEing, and the diabetes link in Alzheimer's disease.
AB  - Diabetes mellitus and Alzheimer's disease (AD) each become increasingly common
      with age. Diabetes causes many chronic end-organ complications and among them is
      dementia, which may be due to an underlying vascular cause, as well as being
      related to AD. The pathogenic mechanisms that lead to diabetes complications
      include advanced glycation end products (AGEs) and growth factor dysregulation.
      This review explores the evidence for epidemiological links between diabetes and
      AD, as well as potential pathogenic mechanisms whereby AGEs, their cellular
      receptors, and key growth factors may contribute to AD development and
      progression in diabetes. Directions for future research are also discussed.

PMID- 19387117
TI  - Involvement of toxic AGEs (TAGE) in the pathogenesis of diabetic vascular
      complications and Alzheimer's disease.
AB  - Recent clinical evidence has suggested diabetes mellitus as one of the risk
      factors for the development and progression of Alzheimer's disease (AD).
      Continuous hyperglycemia is a causative factor for diabetic vascular
      complications, and it enhances the generation of advanced glycation end-products
      (AGEs), thereby being involved in the pathogenesis of AD as well. Moreover, there
      is a growing body of evidence to show that the interaction of glyceraldehyde
      derived AGEs (Glycer-AGE), which is a predominant structure of toxic AGEs (TAGE),
      with a receptor for AGEs elicits oxidative stress generation in numerous types of
      cells, all of which could contribute to the pathological changes of diabetic
      vascular complications and AD. Indeed, we have recently found that Glycer-AGE
      induces apoptotic cell death in cultured cortical neuronal cells. We also found
      that the neurotoxic effect of diabetic serum on neuronal cells was blocked by a
      neutralizing antibody raised against the Glycer-AGE epitope. Moreover, in human
      AD brain, Glycer-AGE is distributed in the cytosol of neurons in the hippocampus.
      These results suggest that Glycer-AGE is involved in the pathogenesis of AD. In
      this review, we discuss the pathophysiological role for AGEs in the development
      and progression of diabetic vascular complications and AD, especially focusing on
      TAGE.

PMID- 19387116
TI  - RAGE and Alzheimer's disease: a progression factor for amyloid-beta-induced
      cellular perturbation?
AB  - Receptor for Advanced Glycation Endproducts (RAGE) is a multiligand member of the
      immunoglobulin superfamily of cell surface molecules which serves as a receptor
      for amyloid-beta peptide (Abeta) on neurons, microglia, astrocytes, and cells of
      vessel wall. Increased expression of RAGE is observed in regions of the brain
      affected by Alzheimer's disease (AD), and Abeta-RAGE interaction in vitro leads
      to cell stress with the generation of reactive oxygen species and activation of
      downstream signaling mechanisms including the MAP kinase pathway. RAGE-mediated
      activation of p38 MAP kinase in neurons causes Abeta-induced inhibition of long
      term potentiation in slices of entorhinal cortex. Increased expression of RAGE in
      an Abeta-rich environment, using transgenic mouse models, accelerates and
      accentuates pathologic, biochemical, and behavioral abnormalities compared with
      mice overexpressing only mutant amyloid-beta protein precursor. Interception of
      Abeta interaction with RAGE, by infusion of soluble RAGE, decreases Abeta content
      and amyloid load, as well as improving learning/memory and synaptic function, in
      a murine transgenic model of Abeta accumulation. These data suggest that RAGE may
      be a therapeutic target for AD.

PMID- 19387118
TI  - Vascular factors in diabetes and Alzheimer's disease.
AB  - The homeostasis of neuronal cells is maintained by the cerebral circulation and
      blood-brain barrier. In addition to age-related physiological decline, diabetes
      disturbs microvascular functions through mechanisms, including activation of
      protein kinase C, excess production of reactive oxygen species and cellular
      activation of the receptor for advanced glycation endproducts (RAGE). Impaired
      microvasculature has been correlated with pathological changes in both vascular
      dementia and Alzheimer's disease. Furthermore, RAGE-mediated chronic inflammation
      initiates a degenerative positive feedback loop between endothelium and neuronal
      cells. The levels of circulating CD34+ cells, which support maintenance of the
      microvasculature and are decreased in diabetes, have been proposed to provide a
      marker of the contribution of cerebrovascular factors in patients with cognitive
      impairment.

PMID- 19387119
TI  - Regulated proteolysis of RAGE and AbetaPP as possible link between type 2
      diabetes mellitus and Alzheimer's disease.
AB  - Epidemiological studies have linked type 2 diabetes mellitus (T2DM) with an
      increased risk of developing Alzheimer's disease (AD). In T2DM, the elevated
      blood glucose level promotes formation of advanced glycation end products (AGEs).
      The receptor for AGEs (RAGE) is a type I membrane-protein and is also able to
      import amyloid-beta (Abeta) from the blood across the blood-brain-barrier into
      the brain. Oligomeric Abeta peptides disturb synaptic function in the brain and
      are believed to contribute to the development of AD. Abeta peptides are released
      from the amyloid-beta protein precursor (AbetaPP) after sequential proteolysis by
      beta- and gamma-secretases but alpha-secretase-mediated cleavage of AbetaPP
      prevents Abeta generation. Insulin influences Abeta production by modulating
      alpha-secretase activity and Abeta degradation. Recent publications demonstrate
      that RAGE is subjected to protein ectodomain shedding. Proteolysis of RAGE occurs
      constitutively and is inducible by activation of protein kinase C. Alpha
      secretase-like enzymes release the ligand binding domain of RAGE from the cell
      surface and after that gamma-secretase processes the membrane-remaining part of
      RAGE. Proteolysis of RAGE may represent a regulatory mechanism in RAGE signal
      transduction and in addition may prevent Abeta peptide transport across the blood
      brain-barrier. Current data suggest that the sequential proteolysis of RAGE is
      homologous to AbetaPP processing.

PMID- 19387120
TI  - Iron toxicity in diseases of aging: Alzheimer's disease, Parkinson's disease and
      atherosclerosis.
AB  - Excess free iron generates oxidative stress that hallmarks diseases of aging. The
      observation that patients with Alzheimer's disease or Parkinson's disease show a
      dramatic increase in their brain iron content has opened the possibility that
      disturbances in brain iron homeostasis may contribute to the pathogenesis of
      these disorders. While the reason for iron accumulation is unknown, iron
      localization correlates with the production of reactive oxygen species in those
      areas of the brain that are prone to neurodegeneration. A role for iron is also
      proposed in atherosclerosis, a further frequent disorder of aging. We will review
      experimental evidences for an involvement of iron in these diseases and discuss
      some mouse models with impairment in iron-related genes that may be useful to
      study the role of iron in these disorders.

PMID- 19387121
TI  - The model Caenorhabditis elegans in diabetes mellitus and Alzheimer's disease.
AB  - Diabetes mellitus, with its complications, and Alzheimer's disease (AD) share
      many similarities. Both are age-related and associated with enhanced formation of
      advanced glycation endproducts (AGEs) and oxidative stress, factors that can be
      observed during the normal aging process as well. AGE deposits can be found in
      areas of atherosclerotic lesions in diabetes and in senile plaques and
      neurofibrillary tangles in AD. A classical model organism in aging research is
      the nematode Caenorhabditis elegans (C. elegans). Though C. elegans lacks a
      vascular system, it has been introduced in diabetes and AD research since it
      shares many similarities at the molecular level to pathological processes found
      in humans. AGEs accumulate in C. elegans, and increased AGE-formation and
      mitochondrial AGE-modification are responsible for increased oxidative stress and
      limiting life span. Moreover, C. elegans has an accessible and well characterized
      nervous system and features several genes homologous to human genes implicated in
      AD like amyloid-beta protein precursor, presenilins and tau. In addition, human
      genes linked to AD, such as amyloid-beta or tau, can be expressed and studied in
      C. elegans. So far, C. elegans research has contributed to a better understanding
      of the function of AD-related genes and the development of this disease.

PMID- 19387122
TI  - Alzheimer research forum live discussion: calcium in AD pathogenesis.

PMID- 19387124
TI  - Prevalence of high-risk human papillomavirus in an inner-city population with
      atypical squamous cells of undetermined significance.
AB  - OBJECTIVE: To compare the prevalence of high-risk human papillomavirus (HPV) in
      patients with atypical squamous cells of undetermined significance (ASCUS)
      cytology in an inner-city clinic and a private office population to determine if
      HPV screening is useful in either group before colposcopy. METHODS: After an
      institutional review board approval at Hartford Hospital, we reviewed the charts
      of patients with ASCUS cytology and high-risk HPV DNA who were seen at the
      Community Health Services, Inc. in Hartford, CT (clinic patients), between
      January 1, 2000, and July 1, 2004, and at a private practice site in Hartford, CT
      (private patients), between January 1, 2004, and December 31, 2004. All charts
      were reviewed for demographic information, history of sexually transmitted
      diseases, tobacco, alcohol, and other drug use. A power analysis indicated that
      32 patients would be needed in each group for a p <.05 with 80% confidence.
      RESULTS: A total of 257 patient's charts were reviewed: 79 clinic charts and 178
      private office charts. Three patients were eliminated due to a lack of HPV
      testing. High-risk HPV was identified in 94.9% of the clinic patients and 45.5%
      of the private patients. The populations were statistically different with regard
      to history of chlamydia (26.6% of clinic patients and 6.2% of private office
      patients; p <.0001), gonorrhea (11.4% clinic patients and 1.1% of private
      patients; p =.0005), and trichomonas (7.6% of clinic patients and 0% of private
      office patients; p =.0007). The prevalence of herpes simplex virus in clinic
      patients was 2.5%, whereas it was present in 6.2% of private patients (p =.35).
      Tobacco use was significantly higher in clinic patients (31.6% of clinic patients
      and 15.2% of private patients; p =.009). CONCLUSIONS: In our study, 94.9% of the
      women in the clinic population with an ASCUS cytology had high-risk HPV compared
      with a rate of 45.5% in the private patients studied. Because most clinic
      patients with ASCUS have high-risk HPV, it is reasonable to defer reflex testing
      for HPV in these high-risk patients and proceed straight to colposcopy.

PMID- 19387125
TI  - Assessing the role of education in women's knowledge and acceptance of adjunct
      high-risk human Papillomavirus testing for cervical cancer screening.
AB  - OBJECTIVE: To assess women's knowledge, concerns, and willingness for adjunct
      high-risk human papillomavirus (HR-HPV) testing before and after an educational
      intervention. MATERIALS AND METHODS: At the time of their annual gynecologic
      examination, women aged 30 years and older received an educational intervention
      about HR-HPV. Subjects completed preintervention and postintervention
      questionnaires. Demographic characteristics were summarized using frequency
      measures. Comparisons between the pre-education and posteducation questionnaires
      were performed using Fisher exact test. RESULTS: Fifty women completed the study.
      After the educational intervention, 77% of women were willing to be tested for HR
      HPV. Sixty-seven percent of women would be likely to return for their annual
      gynecologic examination even if a Pap smear was not required for 3 years.
      Education statistically reduced concern regarding a positive HR-HPV result with
      60% pre-education and 27% posteducation very concerned (p =.002). When surveyed
      about what their concerns would be if tested positive for HR-HPV, women associate
      future cervical cancer diagnosis (38% pre-education vs 48% posteducation, p
      =.903) but not partner infidelity (0%) with testing positive for HR-HPV.
      Knowledge concerning HPV, cervical cancer, and cervical cancer screening was
      statistically improved after the educational intervention in all but 2 questions.
      CONCLUSION: Women 30 years and older are willing to have adjunct HR-HPV testing,
      with education reducing their degree of concern about testing positive. Women who
      test positive would be most concerned about getting cervical cancer. Women would
      be willing to return for yearly gynecologic examinations, even if a Pap smear was
      not needed for 3 years. Education improves women's knowledge of HPV, cervical
      cancer, and cervical cancer screening, but did not allay the concern for getting
      cervical cancer.

PMID- 19387126
TI  - The utility of human papillomavirus testing in the management of atypical
      glandular cells on cytology.
AB  - OBJECTIVE: To determine the value of human papillomavirus (HPV) testing for HPV
      associated cervical disease (HPV-AD) and overall disease (atypical glandular cell
      [AGC]-associated cervical disease) in women with AGCs. MATERIALS AND METHODS: A
      literature search was conducted from January 1993 through September 2007 using
      various AGC-related terms with the exploded Medical Subject Heading (MeSH) term
      "HPV." Findings from 7 studies were used to calculate disease rates according to
      HPV status. RESULTS: The rate of AGC-associated cervical disease for 661 cases of
      AGC with concurrent HPV testing was 23.3%. The rate of HPV-AD was higher in HPV
      positive, versus negative, cases (53% vs 3%, respectively). Human papillomavirus
      positive, versus negative, status predicted a higher likelihood of a cervical
      intraepithelial neoplasia 2/3 lesion (odds ratio = 39.6, 95% CI = 17.9-87.4, p
      <.001). The rate of HPV-nonassociated cancers was significantly higher in
      patients who were negative, versus positive, for HPV (4% vs 0.4%; p =.016). Human
      papillomavirus testing had an overall 90% sensitivity, 79% specificity, 53%
      positive predictive value, and 97% negative predictive value for cases of HPV-AD.
      Atypical glandular cell with concurrent atypical squamous cell (ASC) or squamous
      intraepithelial lesion (SIL) (ASC/SIL) had higher rates of disease than AGC
      alone. The positive predictive value of HPV testing for AGC with concurrent
      ASC/SIL was higher than that for AGC alone. CONCLUSIONS: All women with AGC
      should undergo a comprehensive initial examination regardless of HPV status. The
      presence of HPV identifies a group of women at higher risk for cervical disease
      who should be followed closely. Women positive for human papillomavirus with AGC
      and concurrent ASC/SIL are at even higher risk. If, after a comprehensive initial
      examination, women with AGC not-otherwise-specified and positive HPV have no
      identifiable disease, a cervical conization may be considered.

PMID- 19387127
TI  - High-risk human papillomavirus DNA test results are useful for disease risk
      stratification in women with unsatisfactory liquid-based cytology pap test
      results.
AB  - OBJECTIVES: This study assesses whether high-risk human papillomavirus (HPV) DNA
      test results from residual vial fluid of unsatisfactory liquid-based
      cytology(LBC) samples might provide useful information on disease risk. MATERIALS
      AND METHODS: Patients with unsatisfactory imaged ThinPrep Pap test results and
      available Hybrid Capture 2 high-risk HPV results were identified at an academic
      women's hospital laboratory between July 1, 2005, and July 31, 2007. Follow-up
      repeat cytology results, HPV results, and available biopsy results were analyzed.
      RESULTS: Three hundred four patients with unsatisfactory cytology results and HPV
      test results were studied. Eleven (3.6%) of 304 tested positive for HPV DNA, and
      293 tested HPV negative. Five (45%) of 11 HPV-positive patients had detectible
      low-grade squamous intraepithelial/cervical intraepithelial neoplasia 1 during a
      mean follow-up period of almost 6 months. Among 293 women with negative HPV
      results, only 1 case of cervical intraepithelial neoplasia 1 was identified
      during roughly the same follow-up period. CONCLUSIONS: A positive high-risk HPV
      result associated with an unsatisfactory ThinPrep Pap test result identified
      patients at risk for diagnosis of an undetected squamous intraepithelial/cervical
      intraepithelial neoplasia. Negative high-risk HPV results associated with an
      unsatisfactory LBC had high negative predictive value in this limited study. The
      overall low detection rate for significant disease on follow-up of all patients
      with unsatisfactory imaged LBC is similar to findings reported in another LBC
      study but differs from studies reporting increased risk for undetected disease in
      women screened with unsatisfactory conventional Pap smears.

PMID- 19387128
TI  - Preventing cervical cancer through human papillomavirus vaccination: perspective
      from focus groups.
AB  - OBJECTIVE: It has been a little more than a year ago since the prophylactic
      vaccine against human papillomavirus (HPV) was released in Malaysia. Little is
      known about parental knowledge and acceptability of the vaccine. The objective of
      this study is to assess the mother's knowledge and attitudes toward HPV
      vaccination. The results are aimed to provide insights into the provision of
      appropriate educational and promotional program for effective immunization
      uptake. MATERIALS AND METHODS: Purposive sampling method was adopted for
      recruitment of participants. A total of 47 mothers participated across 8 focus
      group discussions carried out between October and November 2007. The transcribed
      group discussions were analyzed using open-, axial-, and selective-coding
      procedures. RESULTS: Respondents have low awareness about the newly released
      vaccine and the link between HPV and cervical cancer. When provided with
      information about HPV and cervical cancer, most mothers were in favor of
      protecting their daughters from cervical cancer using the vaccine. As with any
      new vaccine, efficacy and safety were the major concern, particularly when the
      vaccine is recommended to preadolescent. Many expressed concern about the high
      cost of the vaccine and hope that the inoculation could be at least partially
      subsidized by the government. A minority were concerned that the sexually
      transmitted disease-related vaccine would promote sexual activities, and some
      opposed making vaccination mandatory. For Muslim respondents, the kosher issue of
      HPV vaccine was an important factor for acceptance. CONCLUSIONS: Developing
      public health messages that focus on the susceptibility of HPV infection and its
      link to cervical cancer to educate parents may have the greatest impact on
      improving the uptake of the vaccine. Apart from the major concern about safety
      and efficacy, affordability, and acceptability of vaccinating young children,
      religious and ethnic backgrounds were important considerations when recommending
      the HPV vaccine. To foster broad acceptance, these issues need to be addressed
      before mass vaccination is pushed forward to the Malaysian public.

PMID- 19387129
TI  - Use of human papillomavirus testing in the management of atypical glandular
      cells.
AB  - OBJECTIVE: To analyze the role of human papillomavirus (HPV) testing in the
      management of women with atypical glandular cells (AGCs). MATERIALS AND METHODS:
      After institutional review board approval, cases of AGC with concurrent HPV
      testing were identified from the pathology database at Hartford Hospital from
      January 2000 to September 2006, inclusive. Atypical glandular cell-associated
      disease included cervical intraepithelial neoplasia 2 (CIN 2) or anything of
      greater pathologic importance on histology. Human papillomavirus-associated
      disease included CIN 2-3, glandular atypia, adenocarcinoma in situ, or any
      cervical malignancy. RESULTS: Two hundred fourteen cases of AGC with concurrent
      HPV testing were evaluated, including 27 cases of AGC with concurrent atypical
      squamous cells, low-grade squamous intraepithelial lesions, or high-grade
      squamous intraepithelial lesions. The rate of disease was 20.6%, with a 7.0%
      prevalence of cancer. Among the 214 cases of AGC, 30.4% tested positive for HPV.
      The rate of HPV-associated disease among cases testing positive for HPV was 40.0%
      compared with 4.0% among HPV-negative cases. The sensitivity of HPV testing for
      HPV-associated disease was 81.3%. Women positive for human papillomavirus were
      less likely to have endometrial or extrauterine disease (1.5%) than HPV-negative
      women (7.4%). CONCLUSIONS: All women with AGC on cervical cytology require
      colposcopy and endocervical curettage regardless of HPV status. Women positive
      for human papillomavirus are at higher risk than HPV-negative women for cervical
      disease and should be evaluated and followed up closely. Women at risk for
      endometrial or extrauterine malignancies should undergo appropriate evaluation
      regardless of HPV status.

PMID- 19387130
TI  - Can recurrence of cervical cancer be predicted by human papillomavirus DNA in
      nodes or plasma?
AB  - OBJECTIVE: To determine if human papillomavirus (HPV) DNA in pelvic lymph nodes
      or plasma of women with early-stage cervical cancer is a marker for recurrence.
      MATERIALS AND METHODS: Twenty-eight women undergoing radical hysterectomy for
      cervical cancer stage IB had HPV DNA testing in cervical tissue, plasma, and the
      largest lymph nodes. Human papillomavirus genotyping was done by restriction
      fragment length polymorphism/line blot assay. Human papillomavirus quantitation
      was performed with specific primers for types 16 and 18. Women were followed up
      to determine recurrence of disease. RESULTS: Human papillomavirus DNA was
      detected in cervical tumor tissue from all the women. Twenty-two women had
      genotype 16, 5 women had HPV18, and 1 had type 31. Human papillomavirus viral
      load in cervical biopsies significantly correlated with the viral loads in the
      lymph nodes (r = 0.97; p = 0). Nine women had nodal metastasis, but only 3 of
      them had HPV DNA in lymph nodes. Recurrence was seen in 4 women, of whom 3 had
      tumor in the lymph nodes at initial surgery and none had HPV. CONCLUSIONS: Human
      papillomavirus DNA can be detected in lymph nodes even when they are not
      obviously involved by tumor metastasis. This study did not show plasma or lymph
      node HPV DNA to be a prognostic marker.

PMID- 19387131
TI  - Surgical excision of strangulated urethral prolapse mimicking urethral carcinoma
      under local anesthesia in a postmenopausal woman.
AB  - Urethral prolapse is frequently reported in girls; however, the clinical
      condition is frequently encountered in postmenopausal women by urologists and
      gynecologists. The treatment of urethral prolapse is controversial. Information
      regarding the treatment and pathophysiology of this clinical entity in
      postmenopausal women is sparse in the published literature. We report a case of
      strangulated urethral prolapse that was successfully treated by surgical excision
      under local anaesthesia.

PMID- 19387132
TI  - Hodgkin lymphoma presenting as a vulvar mass in a patient with crohn disease: a
      case report and literature review.
AB  - OBJECTIVE: A case of Hodgkin lymphoma of the vulva and perineum is presented
      along with a review of the literature. MATERIALS AND METHODS: Medical chart and
      clinical images were reviewed. RESULTS: A 45-year-old female patient with a
      longstanding history of Crohn disease presented with a large vulvar and perineal
      mass. Physical examination revealed a mass measuring approximately 20 x 20 cm
      involving primarily the labia majora, the labia minora, and the clitoris as well
      as the perineum. Incisional biopsy of the vulvar mass revealed histologic
      diagnosis and immunohistochemistry typical of classic Hodgkin lymphoma. Imaging
      revealed involvement of multiple lymph nodes as well as the liver. The patient
      was designated as having stage IV disseminated Hodgkin lymphoma, and chemotherapy
      with doxorubicin, bleomycin, vinblastine, and dacarbazine was instituted. A
      significant reduction of the size of the vulvar mass was observed following 8
      cycles of chemotherapy. CONCLUSIONS.: Lymphoma of the vulva is rare with the
      majority being of the non-Hodgkin lymphoma type. The most common subtypes of
      vulvar lymphoma reported are diffuse large B-cell lymphoma and follicular
      lymphoma. Perianal Hodgkin lymphoma is also very rare but has been reported in
      association with human immunodeficiency virus infection, Epstein-Barr virus
      infection, and Crohn disease. This is only the second reported case of Hodgkin
      lymphoma of the vulva and the second case of Hodgkin lymphoma involving the
      perianal area in a female patient. There is currently no evidence that Crohn
      disease is associated with an increased risk of Hodgkin lymphoma.

PMID- 19387133
TI  - Vulvar cancer and the need for awareness of precursor lesions.
AB  - Vulvar cancer continues to rise in incidence. In the absence of screening,
      attempts to reduce this cancer must focus on recognizing precursor lesions,
      namely, lichen sclerosus and vulvar intraepithelial neoplasia (VIN). The steep
      rise in human papillomavirus-repeated VIN will fall after the introduction of
      vaccination against human papillomavirus; in the meantime, those patients with
      VIN must be treated and then reviewed carefully and frequently. Lichen sclerosus
      has a 3% to 5% risk of progressing to vulvar cancer. Recommendations about which
      patients require referral to and follow-up by specialists/specialist clinics are
      given.

PMID- 19387134
TI  - Clinical question: ask the expert.

PMID- 19387136
TI  - Home study course: spring 2009.
AB  - GLOBAL OBJECTIVE: The Home Study Course is intended for the practicing
      colposcopist or practitioner who is seeking to develop or enhance his/her
      colposcopic skills. The goal of the course is to present colposcopic cases that
      are unusual or instructive in terms of appearance, presentation, or management or
      that demonstrates new and important knowledge in the area of colposcopy or
      pathology. Participants may benefit from reading and studying the material or
      from testing their knowledge by answering the questions. TARGET AUDIENCE: Target
      learners for Home Study Courses are colposcopists in clinical practice and may
      include gynecologists, family physicians, pathologists, residents in training in
      any one of these specialties, gynecologic oncologists, and midlevel providers
      such as nurse practitioners, physician's assistants, and certified nurse
      midwives. ACCME ACCREDITATION: The ASCCP is accredited by the Accreditation
      Council for Continuing Medical Education (ACCME) to provide continuing medical
      education for physicians. The ASCCP designates this education activity for a
      maximum of 1 AMA PRA Category 1 Credit. Physicians should only claim credit
      commensurate with the extent of their participation in the activity.The Home
      Study Course is planned and produced in accordance with the ACCME's Essential
      Areas and Elements and Updated Criteria. DISCLOSURE AND MANAGEMENT OF CONFLICTS
      OF INTEREST: As an accredited provider of CME credit, ASCCP is required to comply
      with the ACCME's Standards of Commercial Support and has implemented a process to
      manage potential conflicts of interest. We have a process to ensure that anyone
      who is in a position to affect the content of the educational activity (e.g.,
      faculty, planners, etc.) has disclosed to us all relevant financial relationships
      with any commercial interest. The ASCCP then discloses to learners any relevant
      financial relationship(s) to include the following information: (1) the name of
      the individual; (2) the name of the commercial interest; and (3) the nature of
      the relationship the person has with each commercial interest. Slides are
      reviewed for possible bias before the course by the Editor, and concerns are
      resolved before publication. Any discussion of off-label use of products is
      noted. Disclosures of these commitments and/or relationships will be published in
      the enduring materials, so those learners in the activity may formulate their own
      judgments regarding the presentation(s). Under ASCCP policy, anyone declining
      either to disclose or amend material to eliminate potential bias identified by
      the Editor will be replaced. DISCLOSURES: : R. Kevin Reynolds, MD (author); L.
      Stewart Massad, MD (Accreditation and Enduring Materials Chair); Deborah L.
      McClain (Home Study Course Staff Administrator); Thomas M. Julian, MD (Journal of
      Lower Genital Tract Disease Executive Editor); and Sandra Smith (Journal of Lower
      Genital Tract Disease Administrative Assistant to the Editor) have no such
      financial relationship or conflict of interest to report.Richard W. Lieberman, MD
      (author): Science and Technology International (consultant).Mark Spitzer, MD
      (Home Study Course Editor): Merck (advisory board, honorarium); Elsevier (book
      author or CD author, royalty); Quest Laboratories (speaker's bureau, honorarium);
      SABK (book author or CD author, royalty)Kathleen G. Poole (ASCCP, Executive
      Director): Pfizer (stockholder); Eli Lilly & Co. (stockholder). DISCLAIMER: : The
      clinical history and images in the Home Study Course may represent an actual
      case, but not always. To improve educational quality, some gross, cytological, or
      histological images may come from photographic libraries. Good teaching cases are
      often difficult to obtain, and we encourage our readers to submit cases with high
      quality images to the Home Study Course Editor or Executive Editor to consider
      for publication. ACKNOWLEDGMENT: All images courtesy of Richard W. Lieberman, MD.

PMID- 19387138
TI  - Policy debate over human papillomavirus vaccines.

PMID- 19387140
TI  - Introduction to the southeastern society of plastic and reconstructive surgeons
      section.

PMID- 19387141
TI  - Effects of perivascular Botulinum Toxin-A application on vascular smooth muscle
      and flap viability in the rat.
AB  - Botulinum toxin-A (BTX) has become a widely used pharmacologic agent for esthetic
      surgeons and those who treat neuromuscular and gastrointestinal conditions. Until
      recently, there has been very little basic science research related to how this
      powerful agent may be useful when applied to vessels. The mechanism of action of
      this agent suggests that it may be useful in treating vasospastic conditions and
      ischemic tissues. We present data from experiments conducted to establish whether
      perivascular application of BTX decreases skin flap necrosis in an island pedicle
      skin flap in the rat. Using an ischemic ventral pedicled island cutaneous flap
      model, 30 adult Sprague-Dawley rats were divided into groups and treated with
      BTX, papaverine, or saline to the intact vascular pedicle to determine the
      percentage of tissue necrosis and ischemia. Flaps were elevated, and the pedicle
      treated with 1 of the 3 agents, and the flaps reinset. Analysis of the percentage
      of flap necrosis and areas of flap ischemia were evaluated on postoperative day
      4. There were no differences in area of flap necrosis between BTX-, papaverine-,
      and saline-treated animal groups. There was a significant decrease in flap
      ischemia in the papaverine-treated group compared with both BTX and saline (P <
      0.01). When necrotic and ischemic areas were combined, papaverine again showed a
      protective effect when compared with the BTX- and saline-treated groups (P <
      0.04). In our ischemic pedicled island cutaneous flap model, papaverine showed
      the greatest protective effect against skin flap ischemia compared with BTX and
      saline. However, our data suggest that BTX may provide a protective effect after
      the first several days following flap elevation.

PMID- 19387142
TI  - The pathophysiology of venous thromboembolism: implications with compression
      garments.
AB  - The highest risk of venous thromboembolism lies with abdominoplasty and
      liposuction and deaths increase when combined with other procedures. The
      objective of this study was to evaluate physiologic changes in the deep venous
      system with compression-garments and asses whether there is a correlation between
      these procedures, rectus plication, and garments. Part 1 of this article is a
      retrospective review of all office surgical incidents that resulted in an
      abdominoplasty and/or liposuction death in the state of Florida over the past 8
      years. Part 2 is a clinical study, evaluating the effect compression garments
      have on the pathophysiology of venous thromboembolism. Duplex ultrasounds were
      performed with and without garments to evaluate venous changes. Literature was
      reviewed related to intraabdominal pressure and high-tension abdominal closures
      and surgeons were polled about their use of rectus plication and
      garments/binders. In 8 years, 13 patients died related to abdominoplasty,
      liposuction, or the combination of the 2. In 100% of subjects, ultrasounds showed
      a decrease in venous flow, proximal vessel dilation, and loss of normal biphasic
      flow within the popliteal vein. Multiple publications have reported an increased
      morbidity and mortality related to liposuction and abdominoplasty procedures. The
      most frequent cause of death with these types of procedures was thromboembolism,
      and we discuss possible reasons for this increased rate. The exact cause of deep
      venous thrombosis in these procedures remains unknown, but postoperative garments
      may affect the physiology of venous flow, and may be involved in the formation of
      deep venous thrombosis and should be considered along with other patient safety
      procedures.

PMID- 19387143
TI  - Perspectives on plastic surgery and global health.
AB  - Of the many factors affecting the health of the human race, those amenable to
      correction by plastic surgical intervention comprise a significant number. The
      interface between the global health community and the plastic surgery community
      historically has been quite diminutive, but this is changing with globalization.
      This overview provides a primer of global health for the plastic surgeon, and a
      discussion of the global burden of disease as it relates to plastic surgery. The
      article then briefly discusses the disparity between the global plastic surgery
      needs and the supply of expertise, and the difficulties presented by policy,
      finances, and implied societal preferences for care.

PMID- 19387144
TI  - Suture suspension technique for midface and neck rejuvenation.
AB  - Seventeen patients averaging 51 years of age underwent 23 surgical procedures,
      including suture suspension for both midface and neck rejuvenations. A 3/0
      polypropylene thread with bioabsorbable cones with multiple point fixations in
      addition to 2 x 0.5-cm polypropylene surgical mesh are used in this technique.
      The mean postoperative, follow-up time was 9 months. Of the 17 patients, 12
      underwent this procedure for midface rejuvenations, 3 for facial palsy, 5 for
      neck aesthetic procedures, 2 for brow ptosis, and 1 for brow asymmetry. The
      average number of sutures used for each face was 4 and 2 were used for each neck.
      The authors present an anatomic study for the safe placement of sutures, the
      surgical technique, and a microscopic photo documentation of the fibrosis around
      the suture knot and cone. All patients developed temporary edema. Two patients
      had a moderate aesthetic improvement of the face, and 1 patient underwent
      resuspension of the sutures 4 months postsurgery. Overall early patient
      satisfaction at 9 months was 90%. This technique has the potential to be a useful
      and effective clinical tool for minimally invasive face and neck rejuvenations.

PMID- 19387145
TI  - Outcomes in threadlift for facial rejuvenation.
AB  - The search for less invasive surgical techniques to address the effects of facial
      aging led to the development of barbed polypropylene sutures for facial
      suspension. Theoretical advantages of these "threadlifts" included limited
      scarring, rapid recovery, relative safety, and reduced cost when compared with a
      standard rhytidectomy. The goal of this study was to evaluate the outcomes of
      patients undergoing threadlifts to determine the actual complication rates, the
      durability of results, and the rates of reoperative surgery. A single surgeon's
      initial 2-year experience with 72 patients undergoing threadlifts was
      retrospectively reviewed. Preoperative patient demographical and clinical data,
      operative information, and postoperative outcomes data were compiled and
      evaluated. A total of 72 thread lifts were performed by 1 surgeon over a 24-month
      period. Of these patients, 76% underwent threadlift alone, whereas concomitant
      procedures were performed in 24% of patients. Minor complications were common and
      usually self-limited. Forty-two percent of patients underwent a secondary
      procedure after primary threadlift, an average of 8.4 months after the original
      surgery. Thirty-one percent of patients required revisional surgery for cosmetic
      reasons an average of 8.7 months after their threadlift. Eleven percent of the
      patients ultimately required removal of palpable threads. Threadlift is a safe
      procedure associated with minor complications. Rates of revisional surgery for
      cosmesis are high after threadlift. Time to revisional surgery for cosmesis is
      short. Results achieved by threadlift are subtle and short-lived. Threadlift is
      not a minimally invasive replacement of surgical rhytidectomy. Patients should
      understand the limitations of this technique and its high rates of revisional
      surgery.

PMID- 19387146
TI  - The combined use of the Ilizarov method and microsurgical techniques for limb
      salvage.
AB  - The purpose of this article is to review clinical outcomes and propose a new
      classification scheme for combined use of Ilizarov Method with free tissue
      transfer for limb salvage. This is an Institutional Review Board-approved
      retrospective review of 62 patients treated with free tissue transfer and
      Ilizarov method over the past 15 years at a single institution. The surgical
      management of these patients is classified into 4 distinct approaches. The mean
      age was 37 years with the most common injury being Gustillo IIIB tibial fractures
      (61%). Eighty-seven percent of patients had failed prior fixation and 63% had
      osteomyelitis with a draining wound. The overall flap survival rate was 97%. The
      mean duration of Ilizarov fixation was 6.9 months with a mean limb length
      correction of 3 cm. The overall rate of primary bony union was 74%. With a mean
      follow-up of 42 months, the combined techniques resulted in limb salvage for 84%
      of cases. Failure of primary bony union was the only predictor of limb
      amputation. This multidisciplinary approach to limb salvage combines
      reconstructive microsurgery and the Ilizarov method.

PMID- 19387147
TI  - Five-year retrospective review of the extended SMAS: critical landmarks and
      technical refinements.
AB  - The beneficial effects of SMAS flap manipulation have been clearly demonstrated
      for the neck and jowls; however, safe limits of subplatysmal dissection in the
      neck have not been established, and recommendations vary widely. Sixty patients
      undergoing rhytidectomy with an extended SMAS flap were retrospectively reviewed
      over a 5-year period. Five critical landmarks for extended SMAS flap dissection
      were marked preoperatively and confirmed intraoperatively. Skin flaps were
      mobilized and redraped independently. All patients were available for follow-up
      at an average of 8.3 months postoperatively (range 5-23 months). There were no
      clinically apparent facial or great auricular nerve injuries or pixy-ear
      deformities. Wound complication rates were acceptably low and included hematoma
      (3%), retroauricular epidermolysis (5%), and temporal scalp alopecia (1.6%).
      Extended SMAS flap dissection allows safe, predictable, and durable correction of
      the neck and jowls. The degree of mobilization proposed in this study allows
      anchoring points of the SMAS flap to be removed from potentially visible and
      palpable areas on the face to the temporal fascia superiorly and the mastoid
      fascia posteriorly. The study also represents a departure from more conventional
      facelifting techniques that advocate dissection of a mesomandibularis.

PMID- 19387148
TI  - Supraclavicular artery flap: a new option for pharyngeal reconstruction.
AB  - Laryngopharyngeal oncologic resections produce complex reconstructive problems,
      requiring dependable robust flaps to restore form and function. Current options
      include morbid local-regional flaps or free tissue transfers. The supraclavicular
      artery flap (SAF) offers a great new option. Partial pharyngeal oncologic defects
      were reconstructed with pedicled SAFs. Handheld Doppler probes marked the pedicle
      preoperatively. Flaps were design based upon the dopplered vascular anatomy.
      Complications and functional outcomes were assessed. All flaps (n = 6) were
      harvested in under 1 hour with uneventful postoperative recoveries. Ablative
      wounds and donor sites were closed primarily. Two patients had small controlled
      leaks because of preoperative radiation and overly aggressive oral intakes, that
      subsequently resolved. There were no functional donor site morbidities. We
      describe a novel application of the SAF for pharyngeal reconstructions after
      laryngopharyngeal cancer ablation. This thin, reliable, easy to harvest, low
      morbidity flap is an excellent reconstructive option for pharyngeal
      reconstructions.

PMID- 19387149
TI  - Overnight observation in stand-alone surgicenters: is the practice safe?
AB  - The safety of performing operations in surgery centers that require overnight
      stays has not been established. To determine whether this practice is safe we
      performed a retrospective chart review of all cases performed at Paces over a 12
      year period. There were 12,072 total cases and 11,147 general anesthesia (GA) or
      monitored anesthesia care (MAC) cases. Four thousand eight hundred ten patients
      stayed overnight. The hospital admission rate for patients undergoing either GA
      or MAC was 0.12% and for local anesthesia it was 0%. Overnight stay patients had
      a rate of 0.15%, while same day discharge patients had a rate of 0.08%. Excluding
      local anesthesia cases, the rate increased to 0.10%. For the GA and MAC patients,
      there was no statistical difference in hospitalization rates between the same day
      and the overnight stay groups. All patients had good outcomes after
      hospitalization. Performing operations that require an overnight stay in a
      surgery center can be a safe practice.

PMID- 19387150
TI  - Composite tissue engineering on polycaprolactone nanofiber scaffolds.
AB  - Tissue engineering has largely focused on single tissue-type reconstruction (such
      as bone); however, the basic unit of healing in any clinically relevant scenario
      is a compound tissue type (such as bone, periosteum, and skin). Nanofibers are
      submicron fibrils that mimic the extracellular matrix, promoting cellular
      adhesion, proliferation, and migration. Stem cell manipulation on nanofiber
      scaffolds holds significant promise for future tissue engineering. This work
      represents our initial efforts to create the building blocks for composite tissue
      reflecting the basic unit of healing. Polycaprolactone (PCL) nanofibers were
      electrospun using standard techniques. Human foreskin fibroblasts, murine
      keratinocytes, and periosteal cells (4-mm punch biopsy) harvested from children
      undergoing palate repair were grown in appropriate media on PCL nanofibers. Human
      fat-derived mesenchymal stem cells were osteoinduced on PCL nanofibers. Cell
      growth was assessed with fluorescent viability staining; cocultured cells were
      differentiated using antibodies to fibroblast- and keratinocyte-specific surface
      markers. Osteoinduction was assessed with Alizarin red S. PCL nanofiber scaffolds
      supported robust growth of fibroblasts, keratinocytes, and periosteal cells.
      Cocultured periosteal cells (with fibroblasts) and keratinocytes showed improved
      longevity of the keratinocytes, though growth of these cell types was randomly
      distributed throughout the scaffold. Robust osteoinduction was noted on PCL
      nanofibers. Composite tissue engineering using PCL nanofiber scaffolds is
      possible, though the major obstacles to the trilaminar construct are maintaining
      an appropriate interface between the tissue types and neovascularization of the
      composite structure.

PMID- 19387152
TI  - Introduction to the northeastern society of plastic surgeons section of annals of
      plastic surgery.

PMID- 19387151
TI  - The incidence of methicillin-resistant staphylococcus aureus in community
      acquired hand infections.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has become increasingly
      prevalent in hand infections. Traditionally, the empiric treatment of hand
      infections has involved beta-lactam antibiotics, which are ineffective against
      MRSA. Centers for Disease Control recommends empiric coverage of MRSA infections
      if the local rate of MRSA exceeds 10% to 15%. A retrospective review was
      performed on all patients admitted for community-acquired soft tissue infections
      of the hand between 2004 and 2007 at a single institution. The overall incidence
      of MRSA was 60%. The incidence of MRSA in healthy adults was 64%, healthy
      pediatric patients was 100%, immunocompromised patients was 45%, and diabetic
      patients was 20%. The current rates of MRSA would imply that all patients
      presenting with hand infections should be treated empirically for MRSA. Linezolid
      is the only oral antibiotic approved by the Food and Drug Administration for
      treating MRSA, but many studies have reported that trimethoprim-sulfamethoxazole
      is an effective antibiotic for outpatient treatment of MRSA.

PMID- 19387153
TI  - Defining the kinetics of breast pseudoptosis after reduction mammaplasty.
AB  - Despite the clinical relevance of bottoming out, or pseudoptosis, associated with
      reduction mammaplasty (RM) its evaluation remains an imprecise science. This
      study aims to further define the kinetics of postoperative pseudoptosis over an
      extended period of time, after our previous study investigating pseudoptosis in
      the early postoperative period. Patients undergoing medial pedicle RM had 3
      dimensional photographs taken at year 1 and year 2 intervals postoperatively
      (year 1 = 300-450 days; year 2 = 700-900 days). Bottoming out was assessed with
      various 3-dimensional parameters. The total breast volume and the percent tissue
      distribution in the upper pole of the breast did not change from year 1 to year
      2. The anterior-posterior projection as well as vector measurements for
      internipple distance and sternal notch to nipple distance also remained stable
      from year 1 to year 2. Although previous data from our group documented the
      occurrence of bottoming out and continued size reduction over the first
      postoperative year after breast reduction, the present study shows that
      pseudoptosis does not seem to occur during the second postoperative year.

PMID- 19387154
TI  - Breast reconstruction for breast asymmetry using recipient site pre-expansion and
      autologous fat grafting: a case report.
AB  - A single case is reported utilizing, recipient site pre-expansion with BRAVA
      (Brava, Inc, Miami, FL) followed by autologous fat grafting to the breast in a
      patient with severe breast asymmetry. Recipient site pre-expansion, used 2 to 3
      weeks before fat grafting and 2 weeks after fat grafting may have both practical
      and theoretical benefits in optimizing the volume and enhancing the survival of
      grafted adipocytes, the mechanism of which is discussed. Recipient site pre
      expansion and fat grafting may have early clinical adoption in cases of severe
      asymmetry, tuberous breasts, and other deformities that are difficult to treat
      with current reconstructive techniques, but studies are needed to clearly
      delineate its safety and its role.

PMID- 19387155
TI  - Wise-pattern breast reconstruction: modification using AlloDerm and a
      vascularized dermal-subcutaneous pedicle.
AB  - Immediate implant-based breast mound reconstruction offers many advantages over
      staged implant reconstruction techniques. For large volume breast reconstruction,
      a Wise-pattern skin resection may provide very good aesthetic results; however,
      the submuscular implant pocket is inadequate to cover the inferior pole of the
      breast. In this patient population, the risk of implant exposure from T-point
      breakdown is significant. We present our technique of Wise-pattern breast
      reconstruction using AlloDerm (LifeCell, Branchburg, NJ) and a vascularized
      dermal-subcutaneous pedicle (DSP) to augment the volume and quality of immediate
      breast implant coverage, particularly in the area of the T-point suture lines. We
      reviewed a series of 20 consecutive patients with large breasts who were treated
      with an immediate implant reconstruction of greater than 400 mL volume using the
      Wise-pattern with DSP. Preoperative and postoperative 3-dimensional surface scan
      studies were performed to evaluate breast symmetry. The average volume of breast
      reconstruction in this study group was 458 mL. T-point breakdown occurred in 5
      patients (25%). These patients were treated with local wound care and healed with
      an excellent aesthetic result. None of these patients required implant removal,
      implant exchange, or operative debridement. Pre- and postoperative 3-dimensional
      surface scan analysis of these patients demonstrated comparable differences
      between the affected and unaffected sides in women undergoing immediate breast
      implant reconstruction when compared with a matched group of patients undergoing
      2-stage breast reconstruction with tissue expanders. Wise-pattern skin-reducing
      mastectomy is an excellent strategy to provide an aesthetically pleasing,
      immediate implant breast reconstruction. This technique provides breast symmetry
      that is at least comparable to that of tissue expander-based, staged implant
      reconstructions. The reliability of the Wise-pattern technique is significantly
      improved with the addition of AlloDerm to the muscular pocket and a vascularized
      DSP to preserve the integrity of the reconstruction in the presence of T-point
      breakdown.

PMID- 19387156
TI  - Improving surgeon confidence in the DIEP flap: a strategy for reducing operative
      time with minimally invasive donor site.
AB  - Criticisms of the DIEP (deep inferior epigastric perforator) flap include
      difficulties in perforator identification and dissection and prolonged operative
      times. Likewise, the stress level in such harvests varies considerably,
      particularly in bilateral breast reconstruction where 2 successful flap harvests
      are mandatory. Various operative strategies were explored in 100s of DIEP flaps
      to refine the DIEP harvest from a safety, expediency, and musculofascial
      preservation perspective, both for total mastectomy and partial mastectomy
      applications. Ultimately, a strategy based on the antegrade pedicle dissection
      technique, usually with a single perforator harvest and discontinuous fascial
      incisions, has lead to a safer, more expeditious and minimally invasive DIEP flap
      harvest that is applicable in many cases. Flap harvest time is now generally on
      the order of one hour with significantly less stress and minimized fascial
      incisions. DIEP free flap harvest can be managed with greater confidence, reduced
      operative times and less muscle, and fascial invasion using the specific
      operative strategy of the antegrade pedicle dissection technique.

PMID- 19387157
TI  - A new diagnostic algorithm for early prediction of vascular compromise in 208
      microsurgical flaps using tissue oxygen saturation measurements.
AB  - The purpose of the study was to evaluate the detection of vascular complications
      earlier than clinical evidence using a noninvasive near-infrared tissue oximeter
      monitor. Early detection of circulatory compromise allows for earlier re
      exploration and better outcomes. The monitoring method studied was the ViOptix
      T.Ox Tissue Oximeter (ViOptix Inc., Fremont, CA). The device uses an optical
      tissue characterization based on measuring scattering and absorption of near
      infrared light. Tissue oxygen saturation and its derivates were evaluated as
      candidates for a more sensitive algorithm to predict vascular flap complications.
      Criteria studied in various combinations were the absolute value of tissue oxygen
      saturation (StO2), the amount of its change (DeltaStO2) and the rate of its
      change (DeltaStO2/Deltat). There were 208 monitored breast flaps in 145 patients
      (62 bilateral and 83 unilateral). In 1 patient, 2 flaps were used to make a
      single breast. Patients were monitored intraoperatively and postoperatively for
      36 hours. No flap being monitored was lost. Among the 208 flaps monitored, 5
      patients exhibited complications that were predicted by the tissue oximeter
      before clinical signs were evident. If blood flow was completely occluded by
      either venous or arterial thrombosis, the tissue oximeter provided information
      that enabled diagnosis to be made in about 1 hour. The drop rate indicator
      DeltaStO2/Deltat, when it is equal to or greater than 20% per hour sustained more
      than 30 minutes predicted vascular complications. The use of the new diagnostic
      algorithm with the T.Ox Tissue Oximeter monitor was successful in predicting flap
      complication within 1 hour of the onset of the occlusive event with a high
      diagnostic accuracy in the 208 flap procedures.

PMID- 19387159
TI  - Minimally invasive correction of inverted nipples: a safe and simple technique
      for reliable, sustainable projection.
AB  - Numerous techniques have been described for the correction of inverted nipples;
      their diversity supports the lack of a consistently reliable method.
      Dermoglandular flaps, open suture, and suction techniques have all been described
      to combat the "corrected" nipple's propensity to collapse. We present a minimally
      invasive parenchymal release and percutaneous suture technique that provides
      sustainable long-term correction of inverted nipples. Thirty-one patients with 58
      inverted nipples were treated. The technique, performed under local anesthesia,
      employs lysis of the foreshortened subareolar fibro-ductal tissue to achieve
      resting eversion of the nipple using an 18-gauge needle. Through the same needle
      access site, a purse-string suture is then placed, exiting the areolar skin and
      re-entering through the same stitch point every 3 to 5 mm around the
      circumference of the new nipple-base. An absorbable suture closes the access site
      over the knot, and 2 crossed absorbable mattress sutures are placed beneath the
      nipple to complete the correction. Of 27 patients with bilateral and 4 with
      unilateral, nipple inversion, durable correction was achieved in 1 procedure in
      45 of 58 nipples (78%). There were 13 recurrences, of which 11 (19%) were
      successfully treated under local anesthesia with a second purse-string suture,
      and 2 (3%) required a third procedure under local anesthesia. There were no late
      reinversions. There were no cases of infection, nipple ischemia, or other
      complications. Occasional recurrences are corrected very simply under local
      anesthesia. Percutaneous release of nipple inversion followed by purse-string
      suture support performed through "needle-only" access points is a simple, safe,
      and reliable technique, and should be considered for the correction of inverted
      nipples.

PMID- 19387158
TI  - Maximizing aesthetics and safety in circumferential-incision lower body lift with
      selective undermining and liposuction.
AB  - Circumferential dermolipectomy has been an effective means of reducing excess
      skin and fat after massive weight loss, however, regions of residual midabdominal
      and epigastric fat frequently confer a suboptimal contour, and often mediocre
      cosmetic results. Liposuction in association with lower body lift surgery has
      been regarded with caution, for fear of ischemia or necrosis of the undermined
      flaps as potential dire consequences. In this study, a theoretical and technical
      approach that maximizes safety and aesthetics in circumferential lower body lift
      after massive weight loss with contouring using liposuction is described and
      evaluated. Twenty-four patients were treated with follow-up ranging from 6 to 40
      months (mean follow-up 17 months). All patients were treated with the resection
      of circumferential skin and fat maintaining a low-lying transverse suture line
      with a prone-to-supine approach. Dorsally, liberal liposuction is performed after
      the instillation of lidocaine-free wetting solution above and below the resection
      lines. Ventrally, the upper flap is elevated widely to the umbilical horizontal.
      The umbilicus is circumcised, and the dissection then progresses in a narrow
      column above the rectus sheaths to the xiphoid. Judicious subcostal undermining
      is performed, maintaining an intact bilateral subcostal "perforator zone" of 4 to
      6 cm. Diastasis repair and anterior sheath plication are performed, and the
      umbilicus is anchored to the fascia. Wetting solution is instilled, and suction
      assisted lipoplasty of the entire flap, particularly in the midline and in the
      region of the neo-umbilicus, is performed, removing excess fat and providing
      discontinuous lateral flap "undermining." There was 1 hematoma (4%) requiring re
      exploration and 4 seromas (17%) treated with percutaneous aspiration. There was
      no infection, skin loss, or wound dehiscence. Unlike standard dermolipectomy
      procedures with wide undermining, the maintenance of a broad subcostal blood
      supply with selective direct undermining allows for liberal flap contouring with
      suction and the establishment of lower suture-line position. With this technique,
      liposuction can be safely used during lower body lift to maximize aesthetic
      outcomes.

PMID- 19387160
TI  - A novel method of auricular reconstruction.
AB  - Seven male patients and 8 total ears underwent composite excision for neoplasm of
      the auricular helix. Defect size ranged from 2.5 to 4.5 cm exceeding the
      conventional limit of l.5 cm for wedge excision with primary closure. An incision
      at the root of the helix released the superior auricular muscle and a portion of
      the strong supporting anterior auricular tendon. An inferior incision allowed for
      the advancement of the lobule. The combined release permitted chondrocutaneous
      mobilization and closure without tension. The cupping deformity was avoided by
      trimming the concha in a wedge excision. Notching was eliminated with a step cut
      and close approximation on closure. The superior auriculocephalic sulcus was
      preserved by altering the fulcrum point of rotation.Ears were reconstructed with
      favorable esthetic outcome with over 1 year of follow-up in 5 of 7 patients. This
      technique represents an alternative method of single stage reconstruction of the
      auricular helix.

PMID- 19387161
TI  - The proximally based peroneal vascular bundle: an insulated extension cord for
      free flap reconstruction.
AB  - Large, traumatic wounds around the proximal third of the lower extremity may have
      disrupted local vasculature, potentially obviating local pedicled options.
      However, free-tissue transfer to this area is technically challenging given the
      resulting paucity of recipient options and the depth of principal blood vessels.
      We present an anatomic and radiographic study of the proximally based peroneal
      vascular bundle as a recipient option in the proximal leg. Optimal approach was
      prone, through an incision over the fibula with dissection between lateral and
      posterior compartments. Magnetic resonance angiography demonstrated consistent
      vascular anatomy between patients. A proximally based peroneal vascular bundle
      protected by a cuff of flexor hallucis longus was used as a recipient vessel in
      free flap reconstruction of an open knee wound. The bundle itself does not
      require coverage by virtue of its own local muscle cuff. Caveats for its use
      include the need for adequate leg inflow and foot outflow.

PMID- 19387162
TI  - Free transverse rectus abdominis myocutaneous and deep inferior epigastric
      perforator flaps for breast reconstruction: a systematic review of flap
      complication rates and donor-site morbidity.
AB  - Free transverse rectus abdominis myocutaneous and deep inferior epigastric
      perforator flaps represent increasingly popular options for breast
      reconstruction. Although several retrospective, small-scale studies comparing
      these flaps have been published, most have failed to find a significant
      difference in flap complication rates or donor-site morbidity. We systematically
      reviewed the current literature, and subsequently pooled and analyzed data from
      included studies. Included studies reported flap complications and/or donor site
      morbidities for both flap types. Eight studies met the inclusionary criteria. For
      flap complications, there was a statistically significant difference between deep
      inferior epigastric perforator and free transverse rectus abdominis myocutaneous
      flaps in fat necrosis rates (25.5 +/- 0.49 vs. 11.3% +/- 0.41%, P < 0.001) and
      total necrosis rates (4.15 +/- 0.08 vs. 1.59% +/- 0.08%, P = 0.044). Partial
      necrosis rates were not statistically significant (3.54 +/- 0.07 vs. 1.60% +/-
      0.07%, P = 0.057). For donor-site morbidity, there was no statistically
      significant difference in abdominal bulge (8.07 +/- 0.23 vs. 11.25% +/- 0.29%, P
      = 0.28). Multicenter, prospective studies are needed to further investigate
      differences between these flap options.

PMID- 19387163
TI  - Management of the difficult sentinel lymph node in patients with primary
      cutaneous melanoma.
AB  - Sentinel lymph nodes (SLN) are examined for occult melanoma metastases for
      accurate staging to dictate optimal therapy. The aim of this case series is to
      discuss clinical challenges in SLN biopsy. Ten challenging cases were identified
      from over 700 melanoma patients with SLN biopsy for primary cutaneous melanoma at
      the Yale Cancer Center Melanoma Unit. These cases were complicated by issues of
      (1) visualization of SLN, (2) concurrent and topographically close melanomas, (3)
      aberrant lymphatic drainage outside standard basins, (4) altered lymphatic
      drainage secondary to surgery, and (5) access to SLN. This case series identifies
      complex clinical scenarios encountered with SLN biopsy that should be familiar to
      a surgeon involved in the surgical care of melanoma patients.

PMID- 19387164
TI  - 3D analysis of breast augmentation defines operative changes and their
      relationship to implant dimensions.
AB  - Breast augmentation is one of the most common plastic surgery procedures
      performed in the United States today. Evaluation of postoperative results lacks
      true objective measurements. The following study reports the application of 3
      dimensional (3D) photography to document changes that occur in breast morphology
      after breast augmentation. Patients undergoing augmentation mammaplasty with a
      periareolar incision were offered pre- and postoperative 3D photographs. 3D
      models were constructed and the following parameters were assessed: maximum
      anterior-posterior projection from the chest wall, angle of breast projection,
      total breast volume, volumetric tissue distribution in the superior and inferior
      poles, and surface and vector distance measurements to key landmarks. A completed
      series of 3D images were obtained from 14 augmentation patients (28 breasts) at
      an average postoperative day of 143. Saline and silicone implants were used
      equally (n = 14 for each). Total volume of the breast changed in correlation with
      the implant size (1.9% difference, P = 0.83). There were no significant changes
      in the volumetric distribution within the upper and lower poles of the breasts
      noted between pre- and postoperative scans (P = 0.81). The internal angle of
      breast projection was found to increase (13.6 degrees, P < 0.01), as did the
      sternal notch to nipple distance (11 mm, P = 0.018). Anterior-posterior
      projection significantly increased by 23.3 mm. However, this increase in
      projection was 20.9% less than expected based on implant dimensions (72.7-58.7
      mm, respectively, P < 0.01). This study documents objective changes in breast
      morphology after augmentation mammaplasty. 3D imaging scans were able to document
      true changes that occur with breast augmentation including breast volume, the
      increase in the internal angle of the breast projection, and the sternal notch to
      nipple distance. 3D photography further highlighted that breast augmentation
      results in less than expected anterior-posterior projection, possibly due to
      tissue attenuation occurring anterior to the implant.

PMID- 19387165
TI  - Gene therapy in skin: choosing the optimal viral vector.
AB  - Skin is an ideal gene therapy target because it is readily accessible and is
      involved in many pathologic processes. Viruses are the most common gene vectors,
      however, few comparative studies exist examining their efficacy in skin. This
      study evaluates adenovirus serotype 5, adeno-associated virus type 2 and 5, MMLV
      derived retrovirus, and human immunodeficiency virus-1 derived lentivirus for
      gene vector activity in human dermal fibroblasts and other skin cell lines. Human
      immunodeficiency virus-1-based lentiviral vector resulted in over 90%
      transduction in all cell lines tested. Transduced cells maintained reporter
      expression over several passages after a single exposure. In contrast, gene
      activity fell rapidly over cell divisions with adenoviral and adeno-associated
      vectors. Therefore, lentiviral vectors are the delivery mechanism of choice for
      long-term therapeutic gene expression in dermal fibroblasts and other skin cell
      lines, whereas adenoviral or adeno-associated vectors may be preferred for short
      term therapy.

PMID- 19387166
TI  - Purse-string closure of hemangiomas: early results of a follow-up study.
AB  - Hemangiomas often leave contour deformities and scarring after involution.
      Surgical resection leaves permanent scars and may distort adjacent anatomy.
      Circular excision with purse-string closure results in the smallest possible scar
      and minimal distortion. Thirty-six patients with varying stages of hemangiomas
      underwent resection with purse-string closure. The dimensions of each hemangioma
      were measured at the time of excision. Dimensions of the scar at follow-up office
      visits were recorded. The final scar was calculated as a percentage of the
      original size of the lesion. Thirty-six patients underwent circular excision and
      purse-string closure of 39 hemangiomas. Thirty (83.3%) were girls and 6 (16.7%)
      were boys. The ages of the patients ranged from 5 months to 13 years, with a
      median age of 2.08. The most common locations were: scalp 9 (23.1%), cheek 9
      (23.1%), forehead 5 (12.8%), and eyebrow 4 (10.3%). The median area of the
      hemangiomas was 491 mm (range: 113-2826 mm2). Follow-up measurements were
      available for 25 patients with 33 hemangiomas. Follow-up ranged from 1 to 22
      months (median follow-up, 3 months). The median area of the purse-string scar was
      70.7 mm (range: 3.925-706.5 mm2). The median percentage reduction in area of
      involvement was 80.6% (range: 24.2%-99.1%). When the hemangiomas were stratified
      into "large" and "small" hemangiomas, the median percentage reduction in the
      areas were 84.1% and 79.2%, respectively. There were 3 complications: 1 patient
      scratched open her incision (ultimately 76% of original size), and 1 toddler
      scraped her scalp against the carpet and dehisced the purse-string closure (final
      size, 43% of original size), and a second toddler fell and dehisced a scalp
      hemangioma (final size, 80% of original size). Traditional lenticular excision of
      hemangiomas results in increased scar length as compared with the original
      lesion. Circular excision and purse-string closure of defects results in a scar
      smaller than the original lesion. It is well tolerated and can be considered the
      default method in most anatomic locations.

PMID- 19387167
TI  - Nipple-sparing mastectomy: evaluation of patient satisfaction, aesthetic results,
      and sensation.
AB  - The purpose of this study is to describe our experience with nipple-sparing
      mastectomy and immediate reconstruction, with particular attention to patient
      satisfaction, aesthetic results, and nipple sensation. Immediate reconstruction
      was performed on 17 breasts in 10 patients, using either implants or autologous
      tissue flaps. Assessment of outcomes was performed through patient interviews, a
      self-reported patient satisfaction survey and review of postoperative
      photographs. Short-term complications included partial loss of the nipple-areolar
      complex requiring debridement (n = 3) and removal of the nipple-areolar complex
      (n = 2) for occult ductal carcinoma in situ. While all patients with completed
      breast reconstructions were satisfied with their general reconstructive
      experience, 6 of 9 patients were aesthetically satisfied with their breast
      reconstruction. Postoperative nipple sensation was reported in 75% of patients,
      although sensation was low (mean of 2.8 of 10). As nipple-sparing mastectomy is
      becoming an increasing patient preference, preoperative discussion needs to
      address expectations, aesthetic satisfaction, and long-term cancer control.

PMID- 19387168
TI  - Surgical outcomes and nipple projection using the modified skate flap for nipple
      areolar reconstruction in a series of 422 implant reconstructions.
AB  - Numerous techniques have been used in an attempt to achieve long-term nipple
      projection following nipple-areolar reconstruction (NAR). A common setback,
      however, is the diminution of projection over time; this phenomenon is
      particularly evident following implant based breast reconstruction. The purpose
      of this report was thus to evaluate surgical outcomes and long-term nipple
      projection with the use of "modified skate flap" technique in exclusively implant
      based postmastectomy reconstructions. A retrospective review was performed for
      the period between 1993 and 2007. All consecutive patients with 2-staged tissue
      expander/implant reconstructions followed by NAR using the modified skate flap
      technique performed by the senior author (P.C.) were identified in a
      prospectively maintained breast reconstruction database. Only patients with a
      minimum of 1-year follow-up were included in the study. Patients with a history
      of irradiation to the breast were excluded from nipple projection assessment.
      Clinical outcome measurements included long-term nipple projection as well as
      incidence of complications from the NAR procedure using the modified skate flap
      technique. Over the 15-year study period, 475 patients underwent 2-staged tissue
      expander/implant reconstruction followed by NAR using the modified skate flap
      technique. Of these, there was a total of 292 patients with the minimum
      requirement of 1-year follow-up post NAR (61% follow-up rate). The total number
      of reconstructed nipple areolar complexes evaluated in this series was 422 (130
      bilateral and 162 unilateral NAR). Forty patients (28 unilateral and 12 bilateral
      NAR) who received radiation to their breasts were excluded from nipple projection
      assessment. At a median follow-up of 44 months (range: 12-84 months), mean nipple
      projection was 2.5 mm (range: 1-4 mm). Minor complications occurred in 7.2% of
      the patients (n = 292). Skin graft donor site dehiscence was the most common
      complication (3.1%) followed by partial skin graft nontake of the areola (2.1%).
      This report documents the largest series of NAR using a single technique in the
      setting of postmastectomy reconstructions. This technique can be safely performed
      over breast implants with acceptably low rates of complications and predictable
      results. Long-term nipple projection over implant reconstructions using this
      technique is modest and this must be forewarned to patients completing the final
      stage of their implant reconstruction.

PMID- 19387171
TI  - Reporting the results of a study that did not go according to plan.

PMID- 19387172
TI  - Cleyer introduces Europeans to acupuncture.

PMID- 19387174
TI  - Volatile anesthetic action in a computational model of the thalamic reticular
      nucleus.
AB  - BACKGROUND: Although volatile anesthetics (VAs) modulate the activity of multiple
      ion channels, the process whereby one or more of these effects are integrated to
      produce components of the general anesthetic state remains enigmatic. Computer
      models offer the opportunity to examine systems level effects of VA action at one
      or more sites. Motivated by the role of the thalamus in consciousness and sensory
      processing, a computational model of the thalamic reticular nucleus was used to
      determine the collective impact on model behavior of VA action at multiple sites.
      METHODS: A computational model of the thalamic reticular nucleus was modified to
      permit VA modulation of its ion channels. Isobolographic analysis was used to
      determine how multiple sites interact. RESULTS: VA modulation of either T-type
      Ca(2+) channels or gamma-aminobutyric acid type A receptors led to increased
      network synchrony. VA modulation of both further increased network
      synchronization. VA-induced decrements in Ca(2+) current permitted greater impact
      of inhibitory currents on membrane potential, but at higher VA concentrations the
      decrease in Ca(2+) current led to a decreased number of spikes in the burst
      generating the inhibitory signal. MAC-awake (the minimum alveolar concentration
      at which 50% of subjects will recover consciousness) concentrations of both
      isoflurane and halothane led to similar levels of network synchrony in the model.
      CONCLUSIONS: Relatively modest VA effects at both T-type Ca(2+) channels and
      gamma-aminobutyric acid type A receptors can substantially alter network behavior
      in a computational model of a thalamic nucleus. The similarity of network
      behavior at MAC-awake concentrations of different VAs is consistent with a
      contribution of the thalamus to VA-induced unconsciousness through action at
      these channels.

PMID- 19387173
TI  - Continuous perioperative insulin infusion decreases major cardiovascular events
      in patients undergoing vascular surgery: a prospective, randomized trial.
AB  - BACKGROUND: A growing body of evidence suggests that hyperglycemia is an
      independent predictor of increased cardiovascular risk. Aggressive glycemic
      control in the intensive care decreases mortality. The benefit of glycemic
      control in noncardiac surgery is unknown. METHODS: In a single-center,
      prospective, unblinded, active-control study, 236 patients were randomly assigned
      to continuous insulin infusion (target glucose 100-150 mg/dl) or to a standard
      intermittent insulin bolus (treat glucose > 150 mg/dl) in patients undergoing
      peripheral vascular bypass, abdominal aortic aneurysm repair, or below- or above
      knee amputation. The treatments began at the start of surgery and continued for
      48 h. The primary endpoint was a composite of all-cause death, myocardial
      infarction, and acute congestive heart failure. The secondary endpoints were
      blood glucose concentrations, rates of hypoglycemia (< 60 mg/dl) and
      hyperglycemia (> 150 mg/dl), graft failure or reintervention, wound infection,
      acute renal insufficiency, and duration of stay. RESULTS: The groups were well
      balanced for baseline characteristics, except for older age in the intervention
      group. There was a significant reduction in primary endpoint (3.5%) in the
      intervention group compared with the control group (12.3%) (relative risk, 0.29;
      95% confidence interval, 0.10-0.83; P = 0.013). The secondary endpoints were
      similar. Hypoglycemia occurred in 8.8% of the intervention group compared with
      4.1% of the control group (P = 0.14). Multivariate analysis demonstrated that
      continuous insulin infusion was a negative independent predictor (odds ratio,
      0.28; 95% confidence interval, 0.09-0.87; P = 0.027), whereas previous coronary
      artery disease was a positive predictor of adverse events. CONCLUSION: Continuous
      insulin infusion reduces perioperative myocardial infarction after vascular
      surgery.

PMID- 19387175
TI  - Connell gas-oxygen apparatus, brass model war SP.

PMID- 19387176
TI  - Reversal of profound neuromuscular block by sugammadex administered three minutes
      after rocuronium: a comparison with spontaneous recovery from succinylcholine.
AB  - BACKGROUND: Rocuronium in intubation doses provides similar intubation conditions
      as succinylcholine, but has a longer duration of action. This study compared time
      to sugammadex reversal of profound rocuronium-induced neuromuscular block with
      time to spontaneous recovery from succinylcholine. METHODS: One hundred and
      fifteen adult American Society of Anesthesiologists Class I-II surgical patients
      were randomized to this multicenter, safety-assessor-blinded, parallel group,
      active-controlled, Phase IIIa trial. Anesthesia was induced and maintained with
      propofol and an opioid. Neuromuscular transmission was blocked and tracheal
      intubation facilitated with 1.2 mg/kg rocuronium or 1 mg/kg succinylcholine.
      Sugammadex (16 mg/kg) was administered 3 min after rocuronium administration.
      Neuromuscular function was monitored by acceleromyography. The primary efficacy
      endpoint was the time from the start of relaxant administration to recovery of
      the first train-of-four twitch (T(1)) to 10%. RESULTS: One hundred and ten
      patients received study treatment. Mean times to recovery of (T(1)) to 10% and
      (T(1)) to 90% were significantly faster in the rocuronium-sugammadex group (4.4
      and 6.2 min, respectively), as compared with the succinylcholine group (7.1 and
      10.9 min, respectively; all P < 0.001). Timed from sugammadex administration, the
      mean time to recovery of (T(1)) to 10%, (T(1)) to 90%, and the train-of-four
      (T(4)/T(1)) ratio to 0.9 was 1.2, 2.9, and 2.2 min, respectively. Reoccurrence of
      the block was not observed. There were no serious adverse events related to study
      treatments. CONCLUSION: Reversal of profound high-dose rocuronium-induced
      neuromuscular block (1.2 mg/kg) with 16 mg/kg sugammadex was significantly faster
      than spontaneous recovery from 1 mg/kg succinylcholine.

PMID- 19387178
TI  - Randomized, double-blind, placebo-controlled, dose-response, and preclinical
      safety study of transforaminal epidural etanercept for the treatment of sciatica.
AB  - BACKGROUND: Recent evidence implicates the inflammatory cytokine tumor necrosis
      factor as a major cause of radiculopathy. Yet, whereas open-label studies with
      systemically delivered tumor necrosis factor inhibitors have yielded positive
      results, a placebo-controlled study failed to demonstrate efficacy. One variable
      that may have contributed to poor outcomes is low drug levels at the site of
      nerve inflammation. To date, no studies have evaluated the efficacy or safety of
      epidurally administered anti-tumor necrosis factor agents. METHODS: A double
      blind, placebo-controlled, dose-response study was conducted to evaluate an
      epidural tumor necrosis factor inhibitor. Twenty-four patients with subacute
      lumbosacral radiculopathy were randomly assigned to receive two transforaminal
      epidural injections of 2, 4, or 6 mg of entanercept 2 weeks apart in successive
      groups of eight. In each group, two patients received epidural saline. A parallel
      epidural canine safety study was conducted using the same injection doses and
      paradigm as in the clinical study. RESULTS: The animal and human safety studies
      revealed no behavioral, neurologic, or histologic evidence of drug-related
      toxicity. In the clinical arm, significant improvements in leg and back pain were
      collectively noted for the etanercept-treated patients, but not for the saline
      group, one month after treatment. One patient in the saline group (17%), six
      patients in the 2-mg group (100%), and four patients each in the 4-mg and 6-mg
      groups (67%) reported at least 50% reduction in leg pain and a positive global
      perceived effect one month after treatment. Six months after treatment, the
      beneficial effects persisted in all but one patient. CONCLUSION: Epidural
      entanercept holds promise as a treatment for lumbosacral radiculopathy.

PMID- 19387179
TI  - Anesthetizing enemy sailors.

PMID- 19387177
TI  - 4G/5G polymorphism of plasminogen activator inhibitor-1 gene is associated with
      mortality in intensive care unit patients with severe pneumonia.
AB  - BACKGROUND: Higher plasma and pulmonary edema fluid levels of plasminogen
      activator inhibitor-1 (PAI-1) are associated with increased mortality in patients
      with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of
      the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence
      of hospitalizations for pneumonia. The authors hypothesized that the 4G allele
      would be associated with worse clinical outcomes (mortality and ventilator-free
      days) in patients with severe pneumonia. METHODS: The authors enrolled patients
      admitted with severe pneumonia in a prospective cohort. Patients were followed
      until hospital discharge. DNA was isolated from blood samples, and genotyping
      detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based
      allelic discrimination. RESULTS: A total of 111 patients were available for
      analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111
      (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital
      discharge and 105 patients (94%) received mechanical ventilation. Patients with
      the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007)
      and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients
      with the 5G/5G genotype. CONCLUSIONS: The 4G allele of the 4G/5G polymorphism in
      the PAI-1 gene is associated with fewer ventilator-free days and increased
      mortality in hospitalized patients with severe pneumonia. These findings suggest
      that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be
      an important biomarker of risk in patients with severe pneumonia.

PMID- 19387180
TI  - The Edison etherizer.

PMID- 19387181
TI  - Pressure and flow(meter).

PMID- 19387183
TI  - Multiplane reconstruction is better than plain X-ray to measure the
      tracheobronchial tree.

PMID- 19387185
TI  - Antiinflammatory effect of peripheral nerve blockade.

PMID- 19387186
TI  - Modified and newly designed right-sided double-lumen endobronchial tubes are
      complementary.

PMID- 19387188
TI  - Infection control practices by the anesthesiologist.

PMID- 19387190
TI  - Increased impedance on nerve stimulator display may actually reflect a decrease
      in total system impedance.

PMID- 19387192
TI  - Nitrous oxide: a global toxicological effect to consider.

PMID- 19387193
TI  - Lumbar plexus or lumbar paravertebral blocks?

PMID- 19387195
TI  - What happens with the fluid replacement in the septic surgical patient?

PMID- 19387197
TI  - Nitric oxide metabolites, platelet activation, and myocardial ischemia
      reperfusion injury.

PMID- 19387199
TI  - Continuous positive airway pressure applied through a bronchial blocker as a
      treatment for hypoxemia due to stenosis of the left main bronchus.

PMID- 19387200
TI  - Tuberculosis of the spine on Tc-99m MDP bone scan: additional role of SPECT-CT.
AB  - Dedicated multislice single-photon emission computed tomography-computed
      tomography (SPECT-CT) is useful for accurate anatomic localization and lesion
      characterization of abnormal findings on planar scintigraphy. We present a case
      of a 33-year-old woman with a history of low back pain. Lumbar spine radiographs
      demonstrated irregularity of the superior end plate of L2 with an associated
      compression fracture. A Tc-99m MDP bone scan was performed given her young age
      and the absence of a history of trauma. The whole body planar imaging revealed
      nonspecific findings of diffuse linear increased tracer uptake involving L2. The
      SPECT-CT findings were in keeping with spinal tuberculosis. This was confirmed
      with culture of CT-guided aspiration of a left psoas collection, which revealed
      heavy growth of Mycobacterium tuberculosis. This case highlights the benefits of
      multislice SPECT-CT imaging in the anatomic localization of increased metabolic
      activity and provision of additional diagnostic information. This enabled rapid
      diagnosis and management.

PMID- 19387201
TI  - Reduced heart rate response to dipyridamole as a marker of left ventricular
      dysfunction in diabetic patients undergoing myocardial perfusion scintigraphy.
AB  - PURPOSE OF THE REPORT: This study sought to find among clinical, hemodynamic and
      left ventricular perfusion and function data obtained from myocardial perfusion
      scintigraphy (MPS), those associated with a reduced heart rate (HR) response to
      dipyridamole in diabetic patients. This phenomenon, although previously described
      as a marker of autonomic dysfunction in patients with diabetes, has not been
      fully elucidated. MATERIALS AND METHODS: One hundred two consecutive diabetic
      patients undergoing dual-isotope (rest Tl-201/dipyridamole stress Tc-99m
      tetrofosmin) MPS were prospectively enrolled. A reduced HR response to
      dipyridamole was considered present if the ratio between maximal HR after
      dipyridamole infusion and rest HR was <or=1.20. MPS images were interpreted
      semiquantitatively, and perfusion scores were calculated. Left ventricular
      ejection fraction (LVEF) was automatically obtained. A logistic regression
      analysis was used to find variables independently associated with a reduced HR
      response to dipyridamole. RESULTS: A reduced HR response to dipyridamole was
      found in 46.1% of the patients and was associated with the presence of chronic
      renal failure (chi2 = 6.4), with high baseline HR (chi2 = 4.7) and low poststress
      LVEF (chi2 = 10.6). CONCLUSIONS: Attenuation of the HR response to dipyridamole
      was frequent and was strongly associated with reduced LVEF. Autonomic dysfunction
      may be reflected in the higher baseline HR but should not be considered the sole
      mechanism accounting for the reduction in HR response to dipyridamole in patients
      with diabetes.

PMID- 19387202
TI  - Case study of anti-1-amino-3-F-18 fluorocyclobutane-1-carboxylic acid (anti-[F
      18] FACBC) to guide prostate cancer radiotherapy target design.
AB  - PURPOSE OF THE REPORT: Anti-1-amino-3-F-18 fluorocyclobutane-1-carboxylic acid
      (FACBC) is a novel radiotracer, which has shown some promise for use with
      positron emission tomography (PET)/computed tomography (CT) for visualizing
      prostate cancer. Here we describe a case of a prostate cancer patient who
      underwent radiation treatment and had an FACBC scan obtained as part of a pilot
      study. METHODS: We explored the potential impact of FACBC on treatment planning.
      We registered the FACBC acquisition with the PET/CT, which required a simple
      translation. Then, we did a deformable image registration of the PET/CT with the
      planning CT-this process allowed the FACBC-defined gross tumor volume (GTVFACBC)
      to be projected into the planning CT. An intensity-modulated radiotherapy (IMRT)
      plan (plan A) not including GTVFACBC (with final dose to 81.0 Gy) was generated,
      as was an IMRT plan including the GTVFACBC to a final dose of 86.4 Gy (plan B).
      Target coverage and normal tissue dose volume histogram (DVH) endpoints were
      tabulated. RESULTS: In this particular patient, bladder constraints could not be
      met on any plan due to anatomic limitations. However, the impact on the rectal
      DVH could be assessed, and inclusion of the GTVFACBC did permit rectal DVH
      constraints to be met in plan B while maintaining target coverage and
      inhomogeneity constraints. CONCLUSION: In our test case, it was feasible to use
      FACBC to guide IMRT, and highlights the role of deformable image registration of
      the PET/CT with the planning CT. These findings can guide future studies
      incorporating FACBC into treatment planning.

PMID- 19387203
TI  - Rim of FDG uptake around a pulmonary infarct on PET/CT in a patient with
      unsuspected pulmonary embolism.

PMID- 19387204
TI  - F-18 flurodeoxyglucose negative, F-18 fluoride accumulating in a brain metastasis
      in a treated case of carcinoma of the breast.

PMID- 19387205
TI  - Tc-99m HMPAO-SPECT with CT attenuation correction improves detection of
      epileptogenic areas.

PMID- 19387206
TI  - Umbilical metastasis from breast cancer detected by FDG PET.

PMID- 19387207
TI  - Breast carcinoma metastatic to renal oncocytoma detected on F-18-FDG PET/CT.

PMID- 19387208
TI  - The identification of a tumor of the cervix on PET/CT with bladder filling and
      emptying.

PMID- 19387209
TI  - Primary cardiac lymphoma evaluated with integration of PET/CT and contrast
      enhanced CT.

PMID- 19387210
TI  - Dual primary subclavicular angiosarcoma and lung cancer imaging with C-11 acetate
      PET and FDG PET.

PMID- 19387211
TI  - F-18 FDG PET/CT of polymyalgia rheumatica.

PMID- 19387212
TI  - Increased thallium-201 accumulation in the transplanted lung.

PMID- 19387213
TI  - Delayed epiphyseal closure seen on Tc-99m methylene disphosphonate bone scan in
      association with hypopituitarism.

PMID- 19387214
TI  - Detection of solitary humeral metastasis from pancreatic adenocarcinoma with F-18
      FDG PET/CT.

PMID- 19387215
TI  - F-18 FDG PET/CT findings of a case of complete hydatidiform mole.

PMID- 19387216
TI  - Faster radioiodine washout in the treatment of pulmonary metastases of papillary
      thyroid cancer prepared with recombinant human thyroid-stimulating hormone.

PMID- 19387217
TI  - Gallium scan-prompted skin biopsy revealed intravascular large B-cell lymphoma in
      a patient who presented with fever of unknown origin.

PMID- 19387218
TI  - Asymmetric FDG uptake in the extraocular muscles resulting from oculomotor nerve
      paralysis.

PMID- 19387219
TI  - Recurrent falls resulting in pseudoaneurysm of a calcified femoral artery.

PMID- 19387220
TI  - FDG PET/CT findings of mesenchymal hamartoma of the liver in an adult.

PMID- 19387222
TI  - Current readings in nuclear medicine.

PMID- 19387221
TI  - F-18 FDG PET/CT as a noninvasive diagnostic and follow-up tool in brown tumors
      due to secondary hyperparathyroidism.

PMID- 19387223
TI  - Pediatric herpes simplex virus keratitis.
AB  - PURPOSE: To report the clinical characteristics and visual outcomes of pediatric
      herpes simplex virus (HSV) keratitis. METHODS: The medical records of 29 patients
      younger than 16 years with HSV keratitis who were diagnosed and treated at Chang
      Gung Memorial Hospital, Taoyuan, Taiwan, between 1996 and 2004 were
      retrospectively reviewed. The diagnosis of HSV keratitis was proven by a positive
      viral culture and/or real-time quantitative polymerase chain reaction or by a
      clear history of dendritic keratitis or herpetic kerato-uveitis. Type of HSV
      keratitis, recurrence rate, and visual outcome were analyzed. RESULTS: The
      average age at the entry into the study was 5.7 years (range: 7 months to 15
      years). Mean follow-up time was 35.3 months (range: 2-69 months). Epithelial
      keratitis including dendritic and geographic ulcers was noted in 14 eyes, stromal
      keratitis in 2 eyes, stromal keratitis concurrent with epithelial keratitis in 8
      eyes, and endotheliitis in 6 eyes. One patient had sequential involvement of both
      eyes. Thirteen patients (45%) developed recurrent HSV keratitis after the first
      documented episode. Female gender (but not age or the type of keratitis) was
      significantly associated with recurrences. Five patients who were maintained on
      oral valacyclovir prophylaxis up to 1 year had no recurrence during the period.
      Fifteen of 21 patients younger than 8 years of age had best-corrected visual
      acuity available at last follow-up, and 10 patients developed amblyopia.
      CONCLUSIONS: Children with HSV keratitis are at risk for recurrent keratitis and
      amblyopia. Prolonged systemic antiviral prophylaxis may help to prevent such
      consequences.

PMID- 19387224
TI  - Influence of corneal curvature on central and paracentral pachymetry with optical
      coherence tomography.
AB  - PURPOSE: Optical coherence tomography (OCT) has been found to be valuable to
      measure the corneal thickness (CT). The purpose of this clinical study was to
      determine the influence of corneal curvature on central and paracentral
      pachymetry with slit lamp-adapted OCT using a linear scanning geometry. METHODS:
      In a prospective, comparative observational study, a total of 77 consecutive
      patients (77 eyes) participated. Central and paracentral (4 mm) CT with slit lamp
      adapted OCT (Heidelberg Engineering, Heidelberg, Germany) and with ultrasound
      (US) pachymetry were performed. The corneal curvature was determined with manual
      keratometry, and the influence of the corneal curvature on CT with OCT was
      compared with curvature-independent US values. RESULTS: The overall mean central
      CT values were 533 +/- 53 microm (OCT) and 546 +/- 56 microm (US) and
      paracentrally 562 +/- 55 microm (OCT) and 569 +/- 55 microm (US). The mean
      central and paracentral differences (P < 0.001) between both methods were 12.7
      and 6.4 microm, respectively. The mean corneal curvature was 7.79 +/- 0.30 mm
      corresponding to a mean corneal power of 43.39 +/- 1.69 diopters. In the central
      area, there was no influence on the OCT measurements (r = -0.01, P = 0.935),
      whereas there was a minimal influence (r = 0.131, P = 0.021) on paracentral
      pachymetry with OCT using a linear scanning module. In paracentral areas, the
      systematic difference between OCT and US decreased from 8.4 microm in flat
      corneas (P < 0.001) to 5.0 microm in steeper corneas (P = 0.06). CONCLUSIONS:
      Slit lamp-adapted OCT allowed noncontact central and paracentral CT measurements.
      Although there were significant differences between OCT and US measurements, the
      corneal curvature had only a minimal influence on paracentral pachymetry with OCT
      using a linear scanning geometry. For more peripheral measurements or in marked
      alterations of the corneal curvature, correction factors may be needed.

PMID- 19387225
TI  - Postkeratoplasty corneal wavefront analysis of selective suture removal.
AB  - PURPOSE: To analyze the corneal wavefront higher order aberrations (HOAs) after
      penetrating keratoplasty and selective suture removal. METHODS: All patients
      undergoing penetrating keratoplasty by the same surgeon (R.K.F.) using identical
      suturing technique were retrospectively identified. Corneal HOAs were calculated
      at the week 6, week 10, 6-month, and final postoperative visits and compared with
      simulated corneal astigmatism, surface regularity index, surface asymmetry index,
      and best-corrected visual acuity. RESULTS: Ninety-two eyes were identified. Total
      corneal HOAs declined from the week 6 visit to the final visit (week 6: 0.65,
      final: 0.50, P = 0.041). Final visit linear regression demonstrated correlations
      of surface asymmetry index and surface regularity index with total corneal HOAs
      (R = 0.51 and R = 0.45, respectively). No relationship for simulated corneal
      astigmatism or vision was found with total corneal HOAs (R = 0.003 and 0.30,
      respectively). CONCLUSIONS: Total corneal HOAs are increased in the early
      postkeratoplasty course, possibly representing the optical consequences of
      surface irregularity. Because simulated keratometry provides no information in
      regard to corneal HOAs, measuring HOAs may be indicated in select cases. Total
      corneal HOAs perhaps provide a clinical representation of irregular astigmatism.
      The visual significance of these total corneal HOAs was not evident.

PMID- 19387226
TI  - Effect of chronic topical glaucoma medications on aerobic conjunctival bacterial
      flora.
AB  - PURPOSE: To investigate whether the chronic topical medications affect aerobic
      conjunctival bacterial flora of patients with glaucoma and to compare their
      findings with the findings of the controls. METHODS: Eighty-one patients and 67
      healthy control subjects participated in this case-control study. Duplicate
      conjunctival swab specimens were collected from each patient at the microbiology
      laboratory and were investigated for the presence of aerobic bacteria. All
      bacterial species from isolated colonies were identified. RESULTS: Thirty seven
      (45.7%) of the 81 patients and 25 (37.3%) of 67 controls had positive
      conjunctival cultures. Coagulase-negative Staphylococcus was the most commonly
      isolated bacterial species in both groups. There were no statistically
      significant differences between the prevalence of other conjunctival cultures
      testing positive for any of the isolated organisms. The patients were also
      evaluated with respect to the presence of a systemic illness. Age, sex, presence
      of diabetes and asthma, duration of antiglaucomatous medication, and number of
      medications used did not have an effect on culture positivity in both groups when
      evaluated by logistic regression model. CONCLUSIONS: The conjunctival culture
      positivity was higher in patients with glaucoma than in the healthy controls and
      in patients with diabetes than in patients without diabetes, although both were
      statistically insignificant. Aerobic conjunctival flora of the patients using
      topical glaucoma medications and the controls did not differ. Further studies are
      needed to comment on the clinical importance of these findings.

PMID- 19387227
TI  - Differences between overnight and long-term wear of orthokeratology contact
      lenses in corneal contour, thickness, and cell density.
AB  - PURPOSE: To investigate changes in corneal topography and morphology in human
      eyes wearing orthokeratology (OK) lenses for overnight and over a 5-year period.
      MATERIALS AND METHODS: Fifty-six adults with moderate myopia were assigned to 2
      groups based on age matching: 5-year lens wear (n = 26, 51 eyes) and 1-night lens
      wear (n = 30, 60 eyes). All subjects wore reverse-geometry OK lenses with the
      eyes before 1-night lens wear serving as a control to both the groups. Visual
      acuity, slit-lamp biomicroscopy, confocal microscopy, and corneal topography were
      assessed before and after lens wear. RESULTS: Visual acuity was improved
      satisfactorily with flattening of the central cornea in both lens wear groups.
      Corneal thickness increased extensively in the 1-night lens wear group but only
      paracentrally in the 5-year lens wear group. Central epithelial thinning with a
      decreased density of the basal cells was only observed in the 5-year group.
      Keratocyte density was reduced throughout the entire corneal thickness for the 2
      groups. Endothelium was normal in density and morphology for the 2 groups.
      CONCLUSIONS: Short-term and long-term OK lens wear can effectively correct myopia
      by flattening the cornea. The flattened cornea in the short-term lens wear is
      mainly because of the thickening of the midperipheral cornea. In the long-term
      lens wear, however, this change is associated with thickening of the
      midperipheral cornea and thinning of the central corneal epithelium.

PMID- 19387228
TI  - Outcomes of augmented relaxing incisions for postpenetrating keratoplasty
      astigmatism in keratoconus.
AB  - PURPOSE: To determine the outcomes of augmented relaxing incisions (relaxing
      incisions and counter-quadrant compression sutures) as graft refractive surgery
      (GRS) in keratoconic eyes. PATIENTS AND METHODS: This interventional case series
      included keratoconic eyes undergoing GRS for intolerable amounts of
      postpenetrating keratoplasty (PKP) astigmatism. Relaxing incisions were made in
      the graft-host interface down to Descemet membrane on both sides of the steepest
      meridian. Interrupted 10-0 nylon compression sutures were added in the opposite
      meridian to overcorrect astigmatism. Selective suture removal was initiated after
      3-6 weeks to achieve tolerable amounts of astigmatism. Best-corrected visual
      acuity and refractive and keratometric astigmatisms were compared before and
      after the operation using simple subtraction and vector analysis methods.
      RESULTS: Overall, 77 eyes of 77 patients including 51 (66.2%) male and 26 (33.8%)
      female subjects with mean age of 30.0 +/- 10.2 years at the time of PKP were
      studied. Average follow-up was 61.5 +/- 33.5 months after PKP and 40.8 +/- 29.3
      months after GRS. Mean best-corrected visual acuity improved from 0.31 +/- 0.26
      logMAR (20/40) before GRS to 0.18 +/- 0.12 logMAR (20/30) postoperatively (P <
      0.001). Mean preoperative and postoperative values for refractive astigmatism,
      keratometric astigmatism, and spherical equivalent refractive error were 6.8 +/-
      1.4 and 3.9 +/- 1.6 diopters (D) (P < 0.001), 7.9 +/- 1.9 and 4.5 +/- 2.2 D (P <
      0.001), and -2.0 +/- 2.9 and -3.24 +/- 2.8 D (P < 0.001), respectively. Vector
      analysis demonstrated that refractive and keratometric astigmatisms were reduced
      by 4.8 and 5.9 D, respectively. CONCLUSIONS: GRS using augmented relaxing
      incisions reduces post-PKP astigmatism in keratoconic eyes; however, it causes a
      slight myopic shift.

PMID- 19387229
TI  - Risk factors, microbiological findings, and clinical outcomes in cases of
      microbial keratitis admitted to a tertiary referral center in ireland.
AB  - AIM: To identify the risk factors for, and to report the microbiological findings
      and clinical outcomes of, severe microbial keratitis (MK). METHODS: This was a
      retrospective study of all cases of presumed MK admitted to a tertiary referral
      center over a 2-year period (September 2001 to August 2003). Data recorded
      included demographic data, details relating to possible risk factors, results of
      microbiological studies, clinical findings at presentation, and clinical and
      visual outcomes. RESULTS: Ninety patients were admitted with a diagnosis of
      presumed MK during the study period. The mean age of patients was 45 +/- 32
      years, and the male to female ratio was 47:43 (52.2%:47.7%). Predisposing risk
      factors for MK included contact lens wear (37; 41.1%), anterior segment disease
      (19; 21.1%), ocular trauma (13; 14.4%), systemic disease (5; 5.6%), and previous
      ocular surgery (1; 1.1%). Cultured organisms included gram-negative bacteria (17;
      51.5%), gram-positive bacteria (11, 33.3%), acanthamoeba (2; 6.1%), and fungi (1;
      3%). Visual acuity improved significantly after treatment [mean best-corrected
      visual acuity (+/-standard deviation) at presentation: 0.76 (+/-0.11); mean best
      corrected visual acuity at last follow-up: 0.24 (+/-0.07); P < 0.001]. Secondary
      surgical procedures were required in 18 (20%) cases, and these included punctal
      cautery (1; 1.1%), tissue glue repair of corneal perforation (2; 2.2%),
      tarsorrhaphy (9; 9.9%), Botulinum toxin-induced ptosis (1; 1.1%), penetrating
      keratoplasty (3; 3.3%), and evisceration (2; 2.2%). CONCLUSIONS: Contact lens
      wear remains a significant risk factor for severe MK. MK remains a threat to
      vision and to the eye, but the majority of cases respond to prompt and
      appropriate antimicrobial therapy.

PMID- 19387230
TI  - Recovery time of an optimally secreting meibomian gland.
AB  - PURPOSE: To investigate the times for an optimally secreting meibomian gland
      (OSMG) to be drained of available liquid secretion, to recover with expressible
      liquid secretion, and then to be redrained. METHODS: Twelve subjects with no dry
      eye symptoms and mean age 21.3 +/- 1.9 years were recruited. Lipid layer
      thickness and tear breakup time were measured. The number of meibomian glands
      yielding liquid secretion for both right and left lower eyelids was counted using
      a meibomian gland diagnostic expression device. A single OSMG in the central
      third of the right and left lower eyelids was marked. A second diagnostic
      expression device was used to drain the liquid secretion from each marked gland.
      The times to drain the gland of available liquid secretion, for the drained gland
      to recover, and then be redrained were measured. RESULTS: The mean lipid layer
      thickness and tear breakup time were 98 +/- 44 nm and 12.4 +/- 1.9 seconds. The
      mean time to drain the marked meibomian gland was 12.1 +/- 3.5 seconds, range: 8
      20 seconds; for partial recovery of the drained meibomian gland was 2.17 +/- 0.49
      hours, range: 1.5-2.5 hours; and to redrain the meibomian gland after recovery
      was 5.54 +/- 1.9 seconds, range: 5-10 seconds. CONCLUSIONS: This report shows
      that (1) a single OSMG can be drained of its liquid secretion in 8-20 seconds
      upon application of a constant force of 1 g/mm, and (2) a partial recovery occurs
      after approximately 2 hours, evidenced by detectable liquid secretion which then
      expressed for only half of the original time.

PMID- 19387231
TI  - Thickness measurements of donor posterior disks after descemet stripping
      endothelial keratoplasty with anterior segment optical coherence tomography.
AB  - PURPOSE: To evaluate donor posterior disk thickness measured with anterior
      segment optical coherence tomography after Descemet stripping endothelial
      keratoplasty. METHODS: Fifteen patients (17 eyes) after Descemet stripping
      endothelial keratoplasty, using manually dissected donor posterior disks, were
      measured with the Visante anterior segment optical coherence tomography (Carl
      Zeiss Meditec Inc, Dublin, CA). Optical coherence tomography scans were made in a
      radial pattern, 45 degrees apart, starting in the horizontal axis. Thickness
      measurements of the donor posterior disks were taken centrally and at fixed radii
      toward the periphery and were correlated to postoperative change in spherical
      equivalent (SE), best-corrected visual acuity (BCVA, in Snellen), and improvement
      in BCVA. RESULTS: Median BCVA was 20/30 (range 20/60-20/20) postoperatively.
      Median postoperative improvement in BCVA was 4 lines (range 1-11). Median follow
      up time was 15.5 months (range 6-32 months). Median postoperative change in SE
      was -0.25 diopters (range -4.25 to +3.00 diopters). Median central disk thickness
      was 128.3 microm (range 55-181 microm) and increased significantly toward the
      periphery: median disk thickness at the 1.5 mm radius was 140.8 microm (range 72
      199 microm) and at the 3.0 mm radius was 161.5 microm (range 102-245 microm). No
      correlation was found between (central) donor disk thickness and postoperative
      BCVA or change in SE. A nonstatistically significant trend was seen toward more
      improvement in BCVA with thinner donor disks. CONCLUSIONS: Optical coherence
      tomography measurements of the manually dissected donor posterior disk showed
      significant variation in thickness, without a statistically significant effect on
      postoperative BCVA or improvement thereof. Central thickness varied significantly
      from the peripheral thickness within donor posterior disk.

PMID- 19387232
TI  - Long-term evaluation of complications and results of photorefractive keratectomy
      in myopia: an 8-year follow-up.
AB  - PURPOSE: To evaluate 8-year results of photorefractive keratectomy (PRK) for
      myopia in terms of safety, efficacy, stability, and late complications. METHODS:
      From 371 myopic eyes of 203 patients who underwent PRK using NIDEK EC-5000
      excimer laser with 5.5- to 6-mm ablation zones in Basir Eye Center, Tehran, Iran,
      during 1997-1998, data of 179 myopic eyes of 98 patients, who participated in
      annual examinations, were analyzed. Treated eyes were divided into 3 groups
      according to preoperative refraction: low myopia [<or=-6.00 diopters (D)],
      moderate myopia (-6.10 to -10.00 D), and high myopia (>-10.00 D). The main
      outcome measures were safety, efficacy, stability, and postoperative
      complications. RESULTS: Eight years after PRK, 69.64%, 44.44%, and 45.65% of the
      low, moderate, and high myopic groups were within +/-0.5 D of emmetropia. Sixteen
      eyes (4.31% of original cases) underwent retreatment mainly because of
      regression. Although a small myopic shift occurred up to 8 years after surgery,
      changes in myopic regression stabilized in all myopic groups within 24 months.
      Four eyes (2.06%) lost 2 lines of best spectacle-corrected visual acuity (1 eye
      for corneal haze and other 3 for problems not related to refractive surgery).
      Corneal haze occurred in 11.34% especially in medium and high myopic groups, but
      it cleared within 2 years in 68.2% of cases. CONCLUSIONS: Based on our study, PRK
      seems to be a safe, efficient, and stable surgical procedure, and if patients
      obtain a good result with the initial treatment, then their results are
      relatively stable over time.

PMID- 19387233
TI  - Short-term corneal response to corneal refractive therapy for different
      refractive targets.
AB  - PURPOSE: The goal of the present study was to investigate the short-term
      variations in corneal topography within the first 3 hours of lens wear under open
      eye conditions, which can be considered an off-label condition in current
      orthokeratology treatment, and the recovery of the effect during an additional 3
      hour period after lens removal. METHODS: Fourteen volunteers were fitted with
      Paragon CRT reverse geometry rigid gas permeable contact lenses simulating 2
      different refractive targets of -2.00 and -4.00 diopters of myopia correction in
      the right and left eyes in random order. After the lenses were placed in both
      eyes, subsequent measurements of corneal topography were obtained at 30, 60, and
      180 minutes; the same measurements were also taken at 30, 60, and 180 minutes
      after lens removal. RESULTS: Significant flattening of the cornea was evident
      after 30 minutes of lens wear. Overall, the -4.00 group changes progressed more
      rapidly than in the -2.00 group, and they also took more time to recover after
      lens removal. However, for most of the parameters, differences between -2.00 and 
      4.00 treatments are evident only after 60 minutes of lens wear. CONCLUSIONS:
      Under open eye conditions, the first 30 minutes of corneal refractive therapy are
      determinant to establish the myopic orthokeratologic effect and changes are
      almost identical irrespective of the refractive target. After this point, changes
      are different depending on the refractive target. The recovery was almost as fast
      as the onset of the orthokeratologic effect, demonstrating that the cornea
      deforms quickly beneath these lenses and does recover safely and quickly once the
      lenses are removed.

PMID- 19387234
TI  - Efficacy and safety of intracameral perfluoropropane (C3F8) tamponade and
      compression sutures for the management of acute corneal hydrops.
AB  - PURPOSE: To assess the efficacy of intracameral perfluoropropane (C3F8) and
      compression sutures in patients with acute corneal hydrops. DESIGN:
      Interventional case series. METHODS: Seventeen patients with acute hydrops were
      treated. Fifteen patients with stromal clefts underwent C3F8 intracameral
      injection with compression sutures and 2 had only C3F8 injection. The time taken
      for the resolution of corneal edema and the best-corrected visual acuity were
      assessed. RESULTS: Of the 17 patients, 11 were males and 6 were females with an
      average age of 15.0 +/- 4.99 years. The presenting visual acuity ranged from hand
      movements to 2/60. The average period between the onset of acute hydrops and
      intracameral injection was 11.0 +/- 10.01 days. The corneal edema resolved in
      8.87 +/- 4.98 days with C3F8 and compression sutures. The average period of
      persistence of bubble in the anterior chamber was 10.75 +/- 2.62 days. No
      complications were noted. Suture removal was done on an average of 3.7 weeks (2-6
      weeks) after the procedure. The average period of follow-up was 6.56 months (1-12
      months). The final best-corrected visual acuity improved in all but 2 cases.
      CONCLUSIONS: The combined use of intracameral gas and compression sutures in
      corneal hydrops with stromal clefts is an effective and safe modality of
      treatment. It also prevents use of repeat gas injection.

PMID- 19387235
TI  - Boston type 1 keratoprosthesis: the university of california davis experience.
AB  - PURPOSE: To compare the University of California Davis experience using the
      Boston keratoprosthesis with the Boston Keratoprosthesis Study Group's initial
      report. DESIGN: Retrospective chart review. PARTICIPANTS: We analyzed 30 eyes of
      28 patients who previously underwent Boston type 1 keratoprosthesis surgery at
      our institution between 2004 and 2008. METHODS: Preoperative, intraoperative, and
      postoperative parameters were collected and analyzed. MAIN OUTCOME MEASURES:
      Visual acuity and keratoprosthesis stability. RESULTS: Preoperative diagnoses
      were failed graft (26 eyes, 87%), chemical injury (3 eyes, 10%), and Stevens
      Johnson syndrome (1 eye, 3%). Twenty eyes (66%) had preoperative glaucoma.
      Preoperative best-corrected visual acuity ranged from 20/150 to light perception
      and was <20/200 in 83% of eyes. At an average follow-up of 19 months (range, 1
      48; SD, 13.8; and median, 13), postoperative vision improved to >or=20/200 in 77%
      of eyes. Among eyes at least 1 year after the operation (16 eyes), vision was
      >or=20/200 in 75% of eyes and >or=20/40 in 25% of eyes. At an average follow-up
      of 19 months, retention of the initial keratoprosthesis was 83.3%. CONCLUSIONS:
      The Boston type 1 keratoprosthesis is a viable option after multiple keratoplasty
      failures or in conditions with a poor prognosis for primary keratoplasty.
      Patients with autoimmune disease are at higher risk for complications. The
      University of California Davis experience seems equivalent to the initial report
      of the Boston Keratoprosthesis Study Group. With longer follow-up, additional
      surgical procedures may be required but good anatomic and functional outcomes can
      be maintained.

PMID- 19387236
TI  - Evaluation of cytotoxic effects of bevacizumab on human corneal cells.
AB  - PURPOSE: Corneal neovascularization contributes to corneal opacification in
      inflammatory conditions of the cornea and severely compromises the success of
      corneal transplantation. Vascular endothelial growth factor (VEGF) plays an
      important role in stimulating and maintaining corneal neovascularization. Anti
      VEGF therapy, especially the use of anti-VEGF antibody bevacizumab, has gained
      popularity in the management of retinal neovascularization and is being used
      topically for corneal neovascularization. The aim of this study was to
      investigate the safety profile of bevacizumab on human corneal cell lines.
      METHODS: Human corneal epithelial and fibroblast cell lines and an umbilical
      vascular endothelial cell line were treated with increasing doses of bevacizumab.
      The effect of this treatment on cell viability was assessed by WST-1 and crystal
      violet staining assays. Cytotoxicity was also assessed by fluorescent microscopy
      and flow cytometric evaluation of propidium iodide-stained cells. RESULTS: In the
      cytotoxicity experiments, there was no difference in cell numbers after 24-hour
      exposure compared with control in any of the cell lines at the concentrations
      tested (P > 0.05 to 0.98). CONCLUSION: Bevacizumab was nontoxic to human corneal
      epithelial and fibroblast cells at 3 different concentrations.

PMID- 19387237
TI  - Intracorneal epithelial ingrowth after descemet stripping endothelial
      keratoplasty and stromal puncture.
AB  - PURPOSE: To report a case of intracorneal epithelial ingrowth after Descemet
      stripping endothelial keratoplasty (DSEK) with stromal puncture for phakic
      bullous keratopathy. METHODS: A 35-year-old man underwent DSEK for phakic bullous
      keratopathy in his right eye after an episode of trauma some years ago.
      Intraoperative drainage of interlamellar fluid was assisted by stromal punctures.
      Postoperatively, the patient had a best-corrected visual acuity of 20/40 in his
      right eye. A small area of epithelial ingrowth appeared in the corneal
      intrastromal interface inferiorly as an irregular flat haze about a month after
      surgery. It was in continuity with the inferior stromal puncture incision made
      intraoperatively. By 10 months, the epithelial pearls became confluent and
      homogenously white with a sharp demarcation. RESULTS: Because the epithelial
      ingrowth remained stationary till the last follow-up (13 months), no surgical
      intervention was planned. The central visual axis was clear and the best
      corrected visual acuity was 20/40. CONCLUSIONS: Epithelial ingrowth into the
      cornea may occur after an uncomplicated DSEK with stromal puncture. Patients
      undergoing DSEK should be closely monitored for development and progression of
      intracorneal epithelial ingrowth, especially when stromal punctures have been
      made to drain interface fluid.

PMID- 19387238
TI  - Descemet stripping automated endothelial keratoplasty in a child with descemet
      membrane breaks after forceps delivery.
AB  - PURPOSE: To report the use of Descemet stripping automated endothelial
      keratoplasty (DSAEK) and to treat visual loss in Descemet membrane (DM) breaks
      after forceps delivery. METHODS: An 8-year-old boy presented with unilateral DM
      ruptures secondary to forceps delivery. Central, vertically oriented DM breaks
      significantly decreased visual acuity. Preoperative visual acuity was 20/80. A
      DSAEK was performed, the DM and endothelium were stripped from the recipient, and
      an 8.5-mm-diameter donor button consisting of posterior stroma and healthy
      endothelium was folded and implanted through a 5-mm incision. An air bubble was
      used to press the donor tissue against the recipient cornea, allowing it to
      attach without sutures. RESULTS: Graft dislocation in the early postoperative
      period required surgical repositioning of the donor lenticule, which led to
      excellent anatomic and functional outcomes. There was a significant and rapid
      improvement of the best-corrected visual acuity, which was 20/50 at the first
      month and 20/32 at the seventh month postoperatively. CONCLUSIONS: To our
      knowledge, this is the first report of a DSAEK in a child with DM tears after
      forceps delivery. Selective replacement of posterior corneal layers with DSAEK
      might be a promising alternative to penetrating keratoplasty to successfully
      treat endothelial or DM lesions during childhood.

PMID- 19387240
TI  - The castroviejo square graft: wound healing after 51 years.
AB  - PURPOSE: To describe the histopathologic characteristics of a 51-year-old
      Castroviejo square graft that remained functional for more than 50 years and to
      describe the wound-healing characteristics over this period of time. METHODS: An
      80-year-old woman with a history of keratoconus underwent penetrating
      keratoplasty with square grafts in 1956 and 1957 in the right and left eyes,
      respectively. The graft from the right eye was replaced in 2007, and the corneal
      specimen was submitted for histopathologic analysis. RESULTS: Light microscopy
      demonstrated a smooth transition between host and donor stroma. Descemet's
      membrane was markedly thickened (>40 m) and laminated, and a very thin
      retrocorneal membrane was visible at high magnification. CONCLUSIONS: This case
      provides an opportunity to observe the histopathology of corneal wound healing
      over a period of more than half a century.

PMID- 19387239
TI  - Calcareous degeneration of host-donor interface after descemet membrane stripping
      with automated endothelial keratoplasty.
AB  - PURPOSE: To report a case of host-donor interface calcification after Descemet
      membrane stripping with automated endothelial keratoplasty (DSAEK). METHODS:
      Review of the patient's clinical records and histopathologic examination of the
      donor corneal lamella from repeat DSAEK performed subsequent to the original
      DSAEK. RESULTS: Review of the clinical record of the patient revealed an ocular
      history of Fuchs dystrophy and pseudophakic bullous keratoplasty that was treated
      with DSAEK. She later developed corneal edema and a partially detached donor
      lamella and underwent repeat DSAEK. Histopathologic and transmission electron
      microscopic evaluations of the corneal lamella revealed calcium deposits in the
      host-donor interface. CONCLUSIONS: Calcareous degeneration of the host-donor
      interface after DSAEK is reported as a novel postoperative complication of DSAEK.
      Calcium deposits in the host-donor interface after DSAEK should be considered in
      the differential diagnosis of interface opacity after this procedure,
      particularly in patients with predisposing systemic or local risk factors such as
      retained phosphate-containing viscoelastic material, excessive postoperative
      inflammation, or use of phosphate-buffered, postoperative topical medications.

PMID- 19387241
TI  - Bilateral acanthamoeba keratitis after orthokeratology.
AB  - PURPOSE: To report bilateral Acanthamoeba keratitis after wearing an overnight
      reverse geometric contact lens for 5 days. METHODS: Case report and review of the
      medical literature RESULTS: A 22-year-old woman developed bilateral corneal
      ulcers during orthokeratology. A slit-lamp examination showed round epithelial
      abrasion, radial infiltration, and disciform keratitis in both corneas. Visual
      acuity OD was hand motion and OS was counting fingers. Bilateral Acanthamoeba
      keratitis was diagnosed by culture by using non-nutrient agar overlaid with
      viable Escherichia coli. Small, round, and double-walled cysts were observed in
      non-nutrient agar under an inverted phase contrast microscope. Topical 0.02%
      polyhexamethylene biguanide, Cravit (0.5% levofloxacin), and Tobra (0.5%
      tobramycin) were administered. After 1 month of treatment, the corneal ulcer had
      healed, and the patient's best-corrected visual acuity was 20/100 OD and 20/25
      OS. CONCLUSIONS: Acanthamoeba keratitis can simultaneously affect both eyes
      during overnight orthokeratology.

PMID- 19387242
TI  - Retention of host embryonic descemet membrane in endothelial keratoplasty.
AB  - OBJECTIVE: To describe a case of retained host embryonic Descemet membrane (DM)
      after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS:
      Review of clinical findings in a case of DSAEK with retention of host embryonic
      DM. RESULTS: A geographic and patchy haze in the interface involving the visual
      axis was noted postoperatively as soon as 1 week after DSAEK surgery. This was
      noted on clinical exam and thought to be retained embryonic DM. Review of
      pathology on the explanted DM confirmed delamination of DM with absence of the
      anterior embryonic layer and only patchy areas of full-thickness DM. The haze was
      followed over time and did not regress over the first 6 months after surgery. It
      did not seem to affect vision significantly, and the patient achieved best
      spectacle-corrected vision of 20/30 by 6 months. CONCLUSIONS: Endothelial
      keratoplasty is a relatively new technique for posterior corneal transplantation.
      Variations in operative technique continue to be described. Delamination of DM
      during stripping can occur; however, retention of host embryonic DM in DSAEK
      surgery seems to be compatible with good vision.

PMID- 19387243
TI  - Necrotic choroidal melanoma with scleritis and choroidal effusion.
AB  - PURPOSE: To report a case of a choroidal melanoma that presented with painful
      scleritis and choroidal effusion. METHODS: Interventional case report with
      cytopathologic correlation. RESULTS: A 78-year-old otherwise healthy woman
      presented with sudden, severe painful ocular inflammation and marked injection of
      the right eye over a 3-day period, consistent with scleritis. Upon referral, 360
      degrees of scleral and conjunctival injection and peripheral choroidal effusion
      were found. In addition, a solid hemorrhagic, choroidal mass was evident,
      suspicious for melanoma. Fine needle aspiration biopsy of the choroidal mass
      confirmed necrotic melanoma. The melanoma was treated with iodine 125 plaque
      radiotherapy, and during surgery, the temporal sclera was markedly edematous and
      the orbital tissue was fibrotic, presumed related to inflammation. Two months
      after radiotherapy, the scleritis and choroidal effusion had resolved.
      CONCLUSION: Uveal effusion can rarely occur with uveal melanoma, particularly
      when the tumor is necrotic.

PMID- 19387244
TI  - In vivo confocal microscopy study of ocular surface neoplasia manifesting after
      radial keratotomy and laser in situ keratomileusis.
AB  - We report a case of ocular surface neoplasia in a patient with history of radial
      keratotomy and laser in situ keratomileusis. In vivo confocal microscopy of the
      cornea was useful to evaluate whether the incisions and scars of previous
      refractive surgeries were involved and to establish appropriate therapy.

PMID- 19387245
TI  - Herpetic epithelial keratitis after intravitreal injection of bevacizumab
      (avastin).
AB  - PURPOSE: To report a case of herpetic epithelial keratitis that developed after
      intravitreal bevacizumab (Avastin) injection. METHODS: A 63-year-old man with
      diabetes with proliferative diabetic retinopathy and macular edema received
      intravitreal injection of bevacizumab (Avastin) in his right eye. RESULTS: Three
      days after the injection, the patient presented with foreign body sensation,
      redness, tearing, photophobia, and decreased visual acuity in the right eye. The
      cornea showed an arborizing dendritic epithelial lesion with terminal bulb
      typical of herpes simplex virus (HSV) epithelial keratitis. HSV-DNA was detected
      in corneal scrapings using polymerase chain reaction. A diagnosis for herpes
      simplex epithelial keratitis was made. Topical acyclovir ointment therapy was
      initiated with good resolution of HSV signs and symptoms. CONCLUSIONS: Herpes
      simplex epithelial keratitis can be a possible complication of intravitreal
      bevacizumab (Avastin) injection. To our knowledge, this case is the first report
      of herpetic epithelial keratitis after intravitreal bevacizumab (Avastin)
      injection.

PMID- 19387246
TI  - Suction loss during femtosecond laser incision for penetrating keratoplasty.
AB  - We present a case of suction loss during a femtosecond laser incision for
      penetrating keratoplasty in the host cornea. This case illustrates a technique
      for completing the procedure with no further complications.

PMID- 19387248
TI  - Coexistent congenital hereditary endothelial dystrophy and congenital glaucoma.

PMID- 19387249
TI  - Analysis of N-terminal pro-B-type natriuretic peptide in patients with acute
      coronary syndromes.
AB  - BACKGROUND: The N-terminal portion of brain natriuretic peptide (NT-proBNP) has
      been identified as an indicator of prognosis in different cardiovascular
      diseases. The objective of this study was to determine the utility of measuring
      plasma NT-proBNP levels in patients with acute coronary syndromes. METHODS AND
      RESULTS: We studied 66 patients admitted in our division for acute coronary
      syndromes. Patients underwent a venous blood sample within 24 h from the
      admission to determine NT-proBNP levels. Increasing plasma levels of NT-proBNP
      (in tertiles) was associated with a greater history of hypertension and current
      smoking, whereas biochemical parameters were associated with higher level of
      creatine kinase-MB mass, cardiac troponin I, and renal insufficiency. We detected
      correlations between the values of NT-proBNP and several variables; positive
      correlations were found between the values of NT-proBNP and creatinine (r=+0354;
      P=0.0024), cardiac troponin I levels (r=0320; P=0.0111), and creatine kinase-MB
      mass values (r=0261; P=0.035). An interesting result of our study was a
      significantly longer hospitalization in those patients belonging to the third
      tertile compared with those belonging to the first one (P=0.02). Finally, we
      showed a higher N-terminal brain natriuretic peptide level in patients with poor
      outcome during the hospitalization (left-ventricular systolic dysfunction,
      recurrent ischemic events, or death) compared with those who did not (3204+/-1841
      vs. 836+/-1136, P=0.003). CONCLUSION: Measurement of B-type natriuretic peptide
      provides predictive information during the hospitalization in patients with acute
      coronary syndromes.

PMID- 19387250
TI  - The diagnostic and prognostic value of tissue Doppler imaging during dobutamine
      stress echocardiography in end-stage renal disease.
AB  - OBJECTIVE: To determine whether a quantitative measurement of peak systolic
      velocity (PSV) during dobutamine stress echocardiography (DSE) detects severe
      coronary artery disease (CAD) and predicts mortality in patients with end-stage
      renal disease. METHODS: One hundred and forty renal transplant candidates had DSE
      and coronary angiography. DSE analysis was performed using conventional visual
      wall motion assessment, longitudinal PSV, and combining the two modalities.
      Failure of PSV to rise by more than 50% predicted an ischemic response.
      Significant CAD was defined as luminal stenosis greater than 70%. RESULTS: The
      number of positive DSE studies according to conventional, PSV, and combined
      criteria was 41 (30%), 42 (31%), and 46 (34%) respectively. Forty patients (29%)
      had significant CAD at angiography. The sensitivity, specificity, positive and
      negative predictive values for conventional DSE analysis were 84, 91, 86, and 90%
      respectively. The same values for PSV analysis were 86, 92, 86, and 91%,
      respectively. The same values for the combination of visual and PSV analysis were
      88, 94, 87, and 92% respectively. The differences between the three methods were
      not statistically significant. Sensitivity for single-vessel CAD (P=0.05) and
      circumflex artery disease (P=0.05) diagnosis was higher with PSV compared with
      conventional DSE analysis. Failure of PSV to rise by more than 50% during DSE was
      associated with significantly increased mortality (P=0.001). CONCLUSION: A
      quantitative interpretation of DSE, based on the percentage rise of PSV during
      stress, accurately detects CAD and predicts prognosis in end-stage renal disease.

PMID- 19387251
TI  - Combination of C-reactive protein and cardiac troponin I for predicting adverse
      cardiac events after sirolimus-eluting stent implantation.
AB  - AIMS: We assessed the predictive value of a combination of C-reactive protein
      (CRP) and cardiac troponin I (cTnI) in a 2-year prospective study in patients
      undergoing sirolimus-eluting stents (SES) implantation. METHODS AND RESULTS: CRP
      and cTnI levels were examined 1 day before and after SES implantation in 322
      patients. CRP level greater than 3.0 mg/l (defining the high serum CRP levels)
      and cTnI level greater than 1.0 microg/l (defining the high serum cTnI levels)
      were considered abnormal. Major adverse cardiac events were defined as nonfatal
      myocardial infarction (MI), target vessel revascularization (TVR), and cardiac
      death. After 2+/-0.2 years of follow-up, there were 11 MI, 19 TVR, and 11 cardiac
      deaths. After adjustment for relevant risk factors, the combination of high CRP
      and cTnI remained predictive of adverse cardiac events, with the presence of both
      elevated CRP and cTnI associated with the highest risks of MI [relative risk
      (RR): 4.0, 95% confidence interval (CI): 2.3-6.4], TVR (RR: 3.3, 95% CI: 2.8
      5.3), and cardiac death (RR: 4.2, 95% CI: 2.6-6.0). The presence of either a high
      CRP or cTnI was associated with an intermediated risk of MI (RR: 1.7, 95% CI: 1.2
      2.2), TVR (RR: 1.5, 95% CI: 1.2-2.7), and cardiac death (RR: 2.8, 95% CI: 2.2
      3.6). CONCLUSION: The combination of elevated CRP and cTnI increased the risk of
      adverse cardiac events, demonstrating the additive impacts of active inflammation
      and myocardial injury on prognosis after SES implantation.

PMID- 19387252
TI  - Bibliography--editors' selection of current world literature.

PMID- 19387254
TI  - Update on viral hepatitis: 2008.
AB  - PURPOSE OF REVIEW: The present review is a concise review of recent developments
      in the field of viral hepatitis, based on publications between December 2007 and
      November 2008. RECENT FINDINGS: The incidence of acute hepatitis A and B
      infection has declined significantly, especially among children less than 15
      years of age. Five oral antiviral agents have been approved for the treatment of
      chronic hepatitis B. Telbivudine is more potent than lamivudine but is associated
      with a high rate of antiviral resistance compared with entecavir or tenofovir. De
      novo combination of lamivudine and adefovir reduces the rate of antiviral
      resistance compared with lamivudine monotherapy. Individualizing dose and
      duration of pegylated interferon and ribavirin according to on-treatment
      virologic response may improve sustained virologic response rates. Several
      specifically targeted antiviral therapies notably protease and polymerase
      inhibitors are promising but must be used in combination with pegylated
      interferon and ribavirin. Hepatitis E virus has been reported to result in
      chronic hepatitis in transplant patients. SUMMARY: Multiple treatment options are
      available for hepatitis B but long-term treatment is required. Several
      specifically targeted antiviral therapies have shown promise. In the meantime,
      individualizing dose and duration of pegylated interferon and ribavirin might
      improve sustained virologic response rates in patients with hepatitis C.

PMID- 19387255
TI  - Pathogenesis of hepatocellular carcinoma and molecular therapies.
AB  - PURPOSE OF REVIEW: Over the past decades, advances in the knowledge of the
      molecular pathogenesis of hepatocellular carcinoma (HCC) have allowed significant
      improvements in the therapeutic management of this devastating disease. Several
      investigations have established the role of aberrant activation of major
      intracellular signaling pathways during human hepatocarcinogenesis. Genome-wide
      analysis of DNA copy number changes and gene expression led to the identification
      of gene signatures and novel targets for cancer treatment. Numerous attempts have
      tried to develop a molecular classification of HCC. This review aims to summarize
      the most relevant genetic alterations and pathways involved in the development
      and progression of HCC, providing an overview of the molecular targeted therapies
      tested so far in human HCC. RECENT FINDINGS: The discovery of sorafenib, a
      multikinase inhibitor, as a treatment with survival benefits in patients with
      advanced HCC, has become a major breakthrough in the clinical management of HCC.
      For the first time, a molecular therapy was able to demonstrate significant
      efficacy for the treatment of HCC patients. New guidelines have established the
      ideal endpoints for the design of clinical trials for HCC. At last, a molecular
      classification of HCC based on genome-wide investigations, able to identify
      patient subclasses according to drug sensitivity will lead to a more personalized
      medicine. SUMMARY: In this review, we provide a comprehensive analysis of the
      underlying molecular mechanisms leading to human hepatocarcinogenesis, providing
      the scientific rationale for the development of new therapeutic targets.

PMID- 19387256
TI  - Autoimmune liver disease.
AB  - PURPOSE OF REVIEW: To review studies that improve the diagnosis and treatment of
      autoimmune hepatitis and extend the understanding of its pathogenic mechanisms.
      RECENT FINDINGS: A simplified diagnostic scoring system has high sensitivity and
      specificity. Biliary changes detected by MRI are of uncertain nature and
      significance. New candidate autoantigens have been identified by proteomic
      analyses. T regulatory cells suppress disease activity; their adoptive transfer
      is beneficial in animal models. Budesonide in combination with azathioprine is
      effective frontline therapy. Bone marrow-derived mesenchymal stem cell
      transplantation may emerge as salvage therapy. Screening for hepatocellular
      cancer is justified. Racial disparities in disease severity, mortality, and
      treatment remain unexplained. SUMMARY: Diagnosis has been simplified and
      management strategies have been upgraded. Biliary changes have been recognized
      but are of uncertain nature and significance. New antigens and antibodies have
      been described. T-cell populations that modulate disease activity have been
      characterized, and adoptive transfer of T regulatory cells is possible.
      Budesonide in combination with azathioprine is effective frontline therapy, and
      therapeutic interventions that target critical pathogenic mechanisms are
      feasible.

PMID- 19387257
TI  - A conceptual proposal for staging ductal cholangiocarcinoma.

PMID- 19387258
TI  - Current world literature.

PMID- 19387262
TI  - T-cell interferon-gamma release assays for the rapid immunodiagnosis of
      tuberculosis: clinical utility in high-burden vs. low-burden settings.
AB  - PURPOSE OF REVIEW: The utility of T-cell interferon-gamma (IFN-gamma) responses
      to Mycobacterium tuberculosis specific antigens [interferon-gamma release assays
      (IGRAs)] in high-burden settings remains unclear and there is growing evidence
      that IGRA performance varies across high tuberculosis (TB) burden vs. low TB
      burden settings. Here we review the evidence supporting the utility of IGRAs in
      specific subgroups and compare their performance in high-burden vs. low-burden
      settings. RECENT FINDINGS: Although the IGRA, compared with the tuberculin skin
      test (TST), has greater specificity in BCG-vaccinated individuals, treatment of
      latent tuberculosis infection is not a priority in high-burden setting.
      Nevertheless, in high-burden settings, the TST performs reasonably well and
      correlates as well, or better, with proxy measures of exposure. SUMMARY: IGRAs
      may still be useful in high-burden settings in specific subgroups at high risk of
      progression, including young children, HIV-infected individuals and healthcare
      workers, but this requires confirmation. Although the IGRAs cannot distinguish
      between latent and active TB, their utility as rule-out tests, when combined with
      smear microscopy or the TST, requires further study. Prospective studies are
      required in high-burden settings to confirm whether IFN-gamma responses are
      predictive of high risk of progression to active TB, particularly in HIV-infected
      individuals.

PMID- 19387263
TI  - Community-acquired pneumonia.
AB  - PURPOSE OF REVIEW: Community-acquired pneumonia (CAP) is a major cause of
      morbidity, mortality and expenditure of resources. When followed, guidelines for
      CAP management have been demonstrated to improve clinical outcomes; however,
      several issues are still open. This review summarizes the recent advances in this
      field and the priority needs for future research. RECENT FINDINGS: Recently
      identified clinical and biochemical tools promise to improve the assessment of
      CAP severity; however, definition of the most accurate and feasible rule(s) for
      clinical practice is now necessary. Some empirical antimicrobial regimens are
      still being debated, such as the need for atypical pathogen coverage in home
      treated and nonsevere hospitalized patients and the inclusion of respiratory
      fluoroquinolones among first-choice molecules. New drugs such as tigecycline and
      cethromycin appear promising. Pharmacokinetically enhanced
      amoxicillin/clavulanate is highly effective, even for treating CAP caused by
      multiple-drug-resistant Streptococcus pneumoniae. Other aspects recently
      clarified include the inappropriateness of rigid time-to-first-antibiotic-dose
      rules, the advantages of shorter antibiotic treatments for nonsevere patients and
      the need of special clinical attention for acute myocardial infarction among
      patients with severe CAP or clinical failure. SUMMARY: Recent developments have
      significantly contributed to refine the management of CAP patients. However,
      various hot topics remain undefined as yet and urgently require ad-hoc research
      in order to optimize the outcomes and the costs of this highly social-impacting
      disease.

PMID- 19387264
TI  - Current world literature.

PMID- 19387266
TI  - Current world literature.
AB  - This bibliography is compiled by clinicians from the journals listed at the end
      of this publication. It is based on literature entered into our database between
      1 January 2008 and 31 December 2008 (articles are generally added to the database
      about two and a half months after publication). In addition, the bibliography
      contains every paper annotated by reviewers; these references were obtained from
      a variety of bibliographic databases and published between the beginning of the
      review period and the time of going to press. The bibliography has been grouped
      into topics that relate to the reviews in this issue.

PMID- 19387267
TI  - Impact of intravenous insulin protocols on hypoglycemia, patient safety, and
      nursing workload.
AB  - The practice of tight glycemic control using an intravenous insulin infusion has
      been adopted in many clinical settings, and although beneficial patient outcomes
      have been clearly documented, the therapy poses potential risks to patient safety
      related to hypoglycemia and increases nursing workload. This article examines
      these issues through a review of current research on tight glycemic protocols.
      Strategies for nurse leaders are provided to improve patient safety and support
      bedside nurses in the administration of insulin infusion protocols.

PMID- 19387269
TI  - Treating agitation with dexmedetomidine in the ICU.
AB  - Patients in the intensive care unit frequently experience delirium, anxiety, and
      agitation, with a variety of treatments used. This article discusses the role of
      an alpha-adrenoceptor agonist, dexmedetomidine, and its clinical relevance and
      advantages for the agitated patient.

PMID- 19387270
TI  - Innovative solutions--the art of improvisation: patient and family preferences
      for visitation in critical care.
AB  - Critical care nurses identified that, although a liberal visitation policy was
      followed, patients and families occasionally expressed preferences for verbal
      communication, rather than have the visitor physically present in the unit.
      Previously tested communication devices interfered with operating equipment
      resulting in poor reception. The purpose of this project was to find an effective
      method for patients to verbally communicate with visitors.

PMID- 19387271
TI  - A personal reflection: dedication.
AB  - A personal account of a U.S. Navy nurse's experiences with a victim of trauma in
      Iraq is presented.

PMID- 19387272
TI  - A personal reflection: what does the general public know about certification of
      critical care nurses?
AB  - This article describes one nurse's views about certification and its importance
      to patient care. The need to educate the public about the value of certification
      is also discussed.

PMID- 19387274
TI  - Using models to teach congenital heart defects: a hands-on approach.
AB  - New pediatric intensive care unit nurses and nursing students often find that
      understanding various congenital heart defects is challenging. This article
      discusses a teaching technique that educators can use when teaching pediatric
      congenital heart defects.

PMID- 19387276
TI  - Risk factors as predictors of sexual activity in heart failure.
AB  - Patients with heart failure (HF) often have concerns about sexual activity while
      living with HF. Little is known about factors that contribute to sexual activity
      and sexual dysfunction in HF. This study examined selected risk factors and
      demographic variables as predictors of sexual activity in HF patients. The sample
      (N = 97) was mostly male and white and had some college education. Four risk
      factors, tobacco use, alcohol use, having diabetes, and number of medications,
      were statistically significant in showing decreased odds of being sexually
      active, when controlling for age, sex, education, and body mass index.
      Nonexercisers and hypertension were not significant predictors of sexual
      activity. Among cardiac medication classes, there were no statistically
      significant differences between those HF patients who were and were not sexually
      active. Health professionals need to be mindful of these predictive factors as
      they provide sexual counseling to patients with HF.

PMID- 19387279
TI  - Data management and security in qualitative research.
AB  - Qualitative research provides rich data on phenomena important to nursing and may
      offer in-depth information for critical care nurses in providing care to their
      patients. Data management, which encompasses topics such as human subjects'
      protection, confidentiality, data storage and record keeping, data ownership, and
      data sharing, is a critical process in qualitative research that deserves
      researchers' attention. Thus, the purpose of this article is to synthesize
      existing research studies on qualitative data management.

PMID- 19387280
TI  - A brief report of student research: mechanism of analgesic effect and efficacy
      and anesthesia interactions of kava in the male Sprague-Dawley rat.
AB  - Use of herbal supplements in the United States continues to grow, and it is
      estimated that approximately 1 in 3 Americans use unconventional therapies to
      relieve pain. Eight herbal supplements have been identified that could pose the
      greatest potential risks in surgical patients. Among these is kava, which is used
      for a wide spectrum of therapeutic properties, including sedative, anxiolytic,
      analgesic, and neuroprotective effects. The purpose of this investigation was to
      examine how kava may modulate pain pathways and how it may interact with morphine
      using the hot-plate analgesia technique.

PMID- 19387283
TI  - National nurses week and the Nightingale pledge.

PMID- 19387285
TI  - Policy: becoming active participants in change.

PMID- 19387286
TI  - Palliative care in the home: an Aotearoa New Zealand perspective.

PMID- 19387287
TI  - Encouraging family caregivers to "step inside the patient's shoes".

PMID- 19387288
TI  - Preventing central line-associated bloodstream infections and the Joint
      Commission's Home Care National Patient Safety Goals.

PMID- 19387290
TI  - Issues in latex allergy in children and adults receiving home healthcare.

PMID- 19387292
TI  - Telehealth: is your staff ready to implement? A descriptive exploratory study of
      readiness for this technology in home health care.

PMID- 19387293
TI  - Caring for vulnerable children in Cambodia.

PMID- 19387294
TI  - Students' perceptions of home visiting.

PMID- 19387295
TI  - Visiting nurse agencies are front and center.

PMID- 19387301
TI  - Uneven operative experience in surgical training: a call for action.

PMID- 19387302
TI  - Specialization: the answer or the problem?

PMID- 19387303
TI  - Adjuvant interferon-based chemoradiation followed by gemcitabine for resected
      pancreatic adenocarcinoma.

PMID- 19387304
TI  - Does laparoscopic-assisted colectomy lead to a better oncologic outcome? Still an
      open question.

PMID- 19387306
TI  - Percutaneous transesophageal gastrostomy (PTEG) is a more acceptable technique
      than cervical pharyngostomy.

PMID- 19387308
TI  - Is laparoscopic appendectomy associated with better outcomes?

PMID- 19387310
TI  - Surgeon volume does not predict outcomes in the setting of technical
      credentialing: results from a randomized trial of colon cancer.

PMID- 19387313
TI  - Neurocognitive evaluation of mild traumatic brain injury in the hospitalized
      pediatric population.
AB  - OBJECTIVE: To test the feasibility of inpatient neurocognitive testing and
      measure the degree of disability in children hospitalized with mild traumatic
      brain injury (MTBI). SUMMARY BACKGROUND DATA: MTBI is common in the pediatric
      population. A standardized approach to identify neurocognitive impairment and
      determine optimal time to return to exertional activities (eg, school, sports) is
      lacking. METHODS: For a 2-year period, children (age: 11-17 years) hospitalized
      at a level 1 urban Pediatric Trauma Center with MTBI were prospectively enrolled.
      Neurocognitive performance was assessed utilizing previously validated computer
      based tests (Immediate Postconcussion Assessment and Cognitive Testing) as
      inpatient and in follow-up clinic after discharge. The feasibility of inpatient
      testing and the degree neurocognitive impairment and symptomatology were
      assessed. This study was approved by the IRB and registered with
      clinicaltrials.gov (NCT00715949). RESULTS: For the 2 years of study, 116 subjects
      were prospectively enrolled and tested. The population had a mean age of 14 years
      and 69.8% were male. On initial in-hospital testing, the overall population
      demonstrated considerable neurocognitive deficits (mean values for all 4 subtests
      below 25th percentile, norm 50%) with at least one subtest score below 25% in
      95.7% and an abnormal symptom score in 83.4% of patients. In comparing initial
      testing to follow-up testing (N = 63), significant improvements were noted for
      all subtests (verbal memory: 28.0% vs. 37.5%, respectively, norm 50%, P = 0.02;
      visual memory: 24.9% vs. 38.1%, respectively, norm 50%, P < 0.01; visual motor:
      21.8% vs. 31.1%, respectively, norm 50%, P = 0.01; reaction time: 21.8% vs.
      30.3%, respectively, norm 50%, P = 0.05), with a decline in the symptom score
      (26.9 vs. 9.2, respectively, norm 0-8, P < 0.01) as well. Patients not seen in
      follow-up (N = 53) did not differ demographically from those seen in clinic.
      CONCLUSIONS: Inpatient neurocognitive testing was feasible in pediatric MTBI
      patients. Neurocognitive abnormalities were nearly universally present on initial
      evaluation with significant improvements demonstrated at the time of outpatient
      follow-up. Return to activity recommendations are thus best deferred for most
      hospitalized MTBI children until formal assessment can be performed after
      discharge.

PMID- 19387314
TI  - Long-term risk of mortality and acute kidney injury during hospitalization after
      major surgery.
AB  - OBJECTIVE: To determine the relationship between long-term mortality and acute
      kidney injury (AKI) during hospitalization after major surgery. SUMMARY
      BACKGROUND DATA: AKI is associated with a risk of short-term mortality that is
      proportional to its severity; however the long-term survival of patients with AKI
      is poorly studied. METHODS: This is a retrospective cohort study of 10,518
      patients with no history of chronic kidney disease who were discharged after a
      major surgery between 1992 and 2002. AKI was defined by the RIFLE (Risk, Injury,
      Failure, Loss, and End-stage Kidney) classification, which requires at least a
      50% increase in serum creatinine (sCr) and stratifies patients into 3 severity
      stages: risk, injury, and failure. Patient survival was determined through the
      National Social Security Death Index. Long-term survival was analyzed using a
      risk-adjusted Cox proportional hazards regression model. RESULTS: In the risk
      adjusted model, survival was worse among patients with AKI and was proportional
      to its severity with an adjusted hazard ratio of 1.18 (95% confidence interval
      [CI], 1.08-1.29) for the RIFLE-Risk class and 1.57 (95% CI, 1.40-1.75) for the
      RIFLE-Failure class, compared with patients without AKI (P < 0.001). Patients
      with complete renal recovery after AKI still had an increased adjusted hazard
      ratio for death of 1.20 (95% CI, 1.10-1.31) compared with patients without AKI (P
      < 0.001). CONCLUSIONS: In a large single-center cohort of patients discharged
      after major surgery, AKI with even small changes in sCr level during
      hospitalization was associated with an independent long-term risk of death.

PMID- 19387315
TI  - Early hypothermia in severely injured trauma patients is a significant risk
      factor for multiple organ dysfunction syndrome but not mortality.
AB  - OBJECTIVE: To evaluate the relationship of early hypothermia to multiple organ
      failure and mortality in a prospectively-collected database of severely injured
      trauma patients. METHODS: This prospective observational study was performed at 7
      level I trauma centers over a 16-month period. Severely injured trauma patients
      with signs of hypoperfusion (eg, base deficit, hypotension) and need for blood
      transfusion during their early hospital course were followed for 24 hours with
      near infrared spectroscopy-derived tissue oxygen saturation (StO2) and other
      variables for 28 days to evaluate outcomes including multiple organ dysfunction
      syndrome (MODS) and death. Early hypothermia was defined as the presence of a
      temperature <35 degrees C [corrected] anytime within the first 6 hours of
      hospitalization. Comparisons between groups were made using the Wilcoxon Two
      Sample test for continuous variables and either the Fisher exact or chi2 test for
      categorical variables. Multivariate logistic regression was utilized to
      understand the effect of hypothermia on outcome (MODS and mortality). RESULTS:
      Hypothermia was very common in this cohort of patients, present in 43% of
      patients enrolled (155/359). Hypothermic patients were 3 times more likely than
      normothermic patients to develop MODS (21% vs. 9%, P = 0.003). Hypothermic
      patients did not have an increased incidence of mortality (16% vs. 12%, P=
      0.2826). Base deficit in hypothermic patients did not discriminate between
      patients who did or did not develop MODS (9.8 +/- 4.6 mEq/L vs. 9.4 +/- 4.4
      mEq/L). In contrast, base deficit in hypothermic patients discriminated with
      respect to mortality (14.6 +/- 7.2 mEq/L versus 9.5 +/- 4.5 mEq/L; P 0.0021), but
      this effect was not observed in normothermic patients [corrected]. Significant
      predictors of MODS using multivariate analysis included minimum StO2 (P= 0.0014)
      and hypothermia (P = 0.0371). Predictors for mortality using multivariate
      analysis included minimum StO2 (P= 0.0021) and base deficit (P= 0.0454), but not
      hypothermia (P= 0.5289). Hypothermia remained a significant risk factor for MODS
      when systolic blood pressure, volume of fluid, and volume of blood infused were
      included in the multivariate model. CONCLUSION: Hypothermia is common in severely
      injured trauma patients (nearly half of patients in this series) and is a
      significant risk factor for MODS but not mortality. The predictive value of base
      deficit for development of MODS is blunted in the presence of hypothermia. A low
      StO2 value predicts MODS and mortality in trauma patients and is a durable
      measure in both normothermic and hypothermic patient groups.

PMID- 19387316
TI  - Predictive factors for ipsilateral or contralateral central lymph node metastasis
      in unilateral papillary thyroid carcinoma.
AB  - OBJECTIVES: To investigate the incidence and the risk factors for occult
      ipsilateral or contralateral central neck lymph node (LN)metastasis in patients
      with unilateral papillary thyroid carcinoma (PTC) and a clinically negative neck.
      SUMMARY BACKGROUND DATA: Elective central lymph node dissection (CLND) in
      patients with PTC remains controversial. There have been few prospective studies
      assessing accurate histopathologic information and predictive factors for the
      presence of metastasis to the ipsilateral or contralateral central compartment of
      the neck in patients with PTC and clinically negative neck nodes. METHODS: We
      reviewed a prospective protocol of 111 unilateral PTC patients with clinically
      node-negative necks who have received total thyroidectomy and elective bilateral
      CLND from 2005 to 2007. The relationships between LN metastasis to the
      ipsilateral or contralateral central neck compartment and clinico-pathologic
      factors such as age, sex, size of primary tumor, perithyroidal invasion,
      lymphovascular invasion, and capsular invasion were analyzed. RESULTS: Occult
      central neck LN metastasis was present in 54.1% (60/111). Of these patients,
      bilateral central LN metastases were present in 50% (30/60), unilateral
      ipsilateral central LN metastasis in 43.3% (26/60), and unilateral contralateral
      central LN metastasis in 6.7% (4/60). In the univariate analysis, the rate of
      ipsilateral central LN metastasis was significantly higher in male patients, high
      risk MACIS score, carcinoma with a maximal diameter of greater than 1 cm, and
      carcinoma with lymphovascular invasion (P < 0.05). The rate of contralateral
      central LN metastasis was significantly higher in cases of carcinoma with a
      maximal diameter of greater than 1 cm, lymphovascular invasion or histologically
      proven metastasis to the ipsilateral central LN (P < 0.05). Multivariate analysis
      showed that the tumor size was an independent risk factor for the presence of
      ipsilateral central LN metastasis, and the presence of ipsilateral central LN
      metastasis was the only independent predictor for the presence of contralateral
      central LN metastasis. CONCLUSIONS: Unilateral PTC with a maximal diameter of
      greater than 1 cm is associated with a high rate of ipsilateral central neck LN
      metastasis. Moreover, ipsilateral central LN metastasis is a potential
      independent predictor of synchronous contralateral central LN metastasis. These
      findings suggest that contralateral as well as ipsilateral elective CLND,
      performed during the initial thyroid operation, may be effective in the
      management of patients with unilateral PTC having a maximal diameter of greater
      than 1 cm and ipsilateral central LN metastasis.

PMID- 19387317
TI  - The value of level III clearance in patients with axillary and sentinel node
      positive breast cancer.
AB  - BACKGROUND: The value of level III axillary clearance is contentious, with great
      variance worldwide in the extent and levels of clearance performed. OBJECTIVE: To
      determine rates of level III positivity in patients undergoing level I-III
      axillary clearance, and identify which patients are at highest risk of involved
      level III nodes. METHODS: From a database of 2850 patients derived from
      symptomatic and population-based screening service, 1179 patients who underwent
      level I-III clearance between the years 1999-2007 were identified. The pathology,
      surgical details, and prior sentinel nodes biopsies of patients were recorded.
      RESULTS: Eleven hundred seventy nine patients had level I-III axillary clearance.
      Of the patients, 63% (n = 747) were node positive. Of patients with node positive
      disease, 23% (n = 168) were level II positive and 19% (n = 141) were level III
      positive. Two hundred fifty patients had positive sentinel node biopsies prior to
      axillary clearance. Of these, 12% (n = 30) and 9% (n = 22) were level II and
      level III positive, respectively. On multivariate analysis, factors predictive of
      level III involvement in patients with node positive disease were tumor size (P <
      0.001, OR = 1.36; 95% CI: 1.2-1.5), invasive lobular disease (P < 0.001, OR =
      3.6; 95% CI: 1.9-6.95), extranodal extension (P < 0.001, OR = 0.27; 95% CI: 0.18
      0.4), and lymphovascular invasion (P = 0.04, OR = 0.58; 95% CI: 0.35-1). Lobular
      invasive disease (P = 0.049, OR = 4.1; 95% CI: 1-16.8), extranodal spread (P =
      0.003, OR = 0.18; 95% CI: 0.06-0.57), and having more than one positive sentinel
      node (P = 0.009, OR = 4.9; 95% CI: 1.5-16.1) were predictive of level III
      involvement in patients with sentinel node positive disease. CONCLUSION: Level
      III clearance has a selective but definite role to play in patients who have node
      positive breast carcinoma. Pathological characteristics of the primary tumor are
      of particular use in identifying those who are at various risk of level III nodal
      involvement.

PMID- 19387318
TI  - Surgeon characteristics and use of breast conservation surgery in women with
      early stage breast cancer.
AB  - BACKGROUND: Most women with localized breast cancer have a choice between
      mastectomy and breast conserving surgery (BCS). Aside from clinical factors, this
      decision may be associated with surgeon and patient characteristics. We
      investigated the effect of surgeon characteristics on the BCS rate. METHODS: We
      used the Surveillance, Epidemiology, and End Results-Medicare database to
      identify women >65 years, diagnosed with stages I-II BC, between 1991 and 2002,
      and used the Physician Unique Identification Number linked to the American
      Medical Association Masterfile to obtain information on surgeons. We investigated
      the association of patient demographic, tumor, and surgeon-related factors with
      receipt of BCS, using Generalized Estimating Equations to control for clustering.
      RESULTS: Of 56,768 women with breast cancer, 30,006 (53%) underwent BCS, whereas
      26,762 (47%) underwent mastectomy. Between 1991 and 2002, the proportion of
      patients undergoing BCS increased from 35% to 60%. In a multivariate analysis,
      patients who received BCS were younger, of higher SES, and had more favorable
      tumor characteristics. They were also more likely to be black and live in
      metropolitan areas. Women who underwent BCS were more likely to have surgeons who
      were female (OR = 1.40; 95% CI: 1.25-1.55), US-trained (OR = 1.12; 95% CI: 1.02
      1.22), with a larger patient panel (OR = 1.29; 95% CI: 1.21-1.39), and completed
      training after 1975 (OR = 1.16; 95% CI: 1.08-1.25), than surgeons of patients who
      underwent mastectomy. CONCLUSIONS: Surgeon characteristics, such as gender,
      training, year of graduation, and volume, are small but significant independent
      predictor of BCS. Efforts to differentiate whether these associations reflect
      patients' preferences, quality of physician training, surgeon attitudes,
      physician-patient communication, or other effects on decision-making are
      warranted.

PMID- 19387319
TI  - Mechanisms of renal phosphate loss in liver resection-associated
      hypophosphatemia.
AB  - OBJECTIVE: To determine precisely the role of parathyroid hormone (PTH) and of
      phosphatonins in the genesis of posthepatectomy hypophosphatemia. BACKGROUND:
      Posthepatectomy hypophosphatemia has recently been related to increased renal
      fractional excretion of phosphate (FE P). To address the cause of
      hypophosphatemia, we measured serum concentrations of PTH, various phosphatonins,
      and the number of removed hepatic segment in patients with this disorder.
      METHODS: Serum phosphate (PO4), ionized calcium (Ca++), HCO3-, pH and FE P,
      intact PTH (I-PTH), carboxyl-terminal fibroblast growth factor 23 (C-FGF-23) and
      intact fibroblast growth factor 23 (I-FGF-23), FGF-7, and secreted frizzled
      related-protein-4 (sFRP-4) were measured before and on postoperative (po) days 1,
      2, 3, 5, and 7, in 18 patients undergoing liver resection. The number of removed
      hepatic segments was also assessed. RESULTS: Serum PO4 concentrations decreased
      within 24 hours, were lowest (0.66 +/- 0.03 mmol/L; P < 0.001) at 48 hours, and
      returned to normal within 5 days of the procedure. FE P peaked at 25.07% +/-
      2.26% on po day 1 (P < 0.05). Decreased ionized calcium concentrations (1.10 +/-
      0.01 mmol/L; P < 0.01) were observed on po day 1 and were negatively correlated
      with increased I-PTH concentrations (8.8 +/- 0.9 pmol/L; P < 0.01; correlation: r
      = -0.062, P = 0.016). FE P was positively related to I-PTH levels on po day 1 (r
      = 0.52, P = 0.047) and negatively related to PO4 concentrations (r = -0.56, P =
      0.024). Severe hypophosphatemia and increased urinary phosphate excretion
      persisted for 72 hours even when I-PTH concentrations had returned to normal. I
      FGF-23 decreased to its nadir of 7.8 +/- 6.9 pg/mL (P < 0.001) on po day 3 and
      was correlated with PO4 levels on po days 0, 3, 5, and 7 (P < 0.001). C-FGF-23,
      FGF-7 and sFRP-4 levels could not be related to either PO4 concentrations or FE
      P. CONCLUSION: Posthepatectomy hypophosphatemia is associated with increased FE P
      unrelated to I-FGF-23 or C-FGF-23, FGF-7, or sFRP-4. I-PTH contributes to
      excessive FE P partially on po day 1 but not thereafter. Other yet defined
      factors should explain post hepatectomy hypophosphatemia.

PMID- 19387320
TI  - Accelerated perinecrotic outgrowth of colorectal liver metastases following
      radiofrequency ablation is a hypoxia-driven phenomenon.
AB  - OBJECTIVE: The aim of this study was to assess how thermal ablation of colorectal
      liver metastases affects the outgrowth of micrometastases in the transition zone
      (TZ) between ablated tissue and the unaffected reference zone (RZ) in 2 different
      murine models. BACKGROUND: Thermal destruction therapies of nonresectable
      colorectal liver metastases, including radiofrequency ablation (RFA), can provide
      tumor clearance, but local recurrences are common. METHODS: Three days after
      intrasplenic injection of C26 colon carcinoma cells, RFA was applied to the left
      liver lobe. Perinecrotic microcirculation, tissue hypoxia, hypoxia inducible
      factor (HIF)-1alpha and HIF-2alpha, and the outgrowth of micrometastases both in
      the TZ and in the RZ were evaluated over time. RESULTS: In 2 different animal
      models, the outgrowth of micrometastases in the TZ following RFA was stimulated
      approximately 4-fold compared to tumor growth in the RZ. Accelerated tumor growth
      in the TZ was associated with microcirculatory disturbances, prolonged hypoxia,
      and stabilization of HIF-1alpha and HIF-2alpha in the tumor cells. In addition,
      RFA induced the formation of new hepatic vessels that sprouted from existing
      sinusoids and grew into the generated necrotic lesion. Surprisingly, the
      accelerated tumor growth was not associated with these vessels. Treatment with
      17DMAG prevented HIF-1alpha and HIF-2alpha stabilization and selectively reduced
      tumor growth in the TZ by approximately 40% without affecting tumor growth in
      sham-operated mice or in the RZ of RFA-treated mice. PTK787/ZK-222584, a
      nonselective Vascular Endothelial Growth Factor (VEGF)-receptor inhibitor,
      reduced RFA-stimulated tumor growth and tumor growth in the RZ to a similar
      extent. CONCLUSIONS: We conclude that RFA stimulates the outgrowth of tumor cells
      at the lesion periphery. Angiogenesis is not the driving force behind RFA
      stimulated tumor growth, but other hypoxia/HIF-activated pathways are likely to
      be important.

PMID- 19387321
TI  - A phosphodiesterase III inhibitor protects rat liver from sinusoidal obstruction
      syndrome through heme oxygenase-1 induction.
AB  - OBJECTIVE: The aim of study was to investigate pharmacological treatment for
      sinusoidal obstruction syndrome (SOS). BACKGROUND: SOS is associated with
      oxaliplatin-based chemotherapy in patients with hepatic colorectal metastases.
      Patients with SOS have increased postoperative morbidity after major hepatectomy,
      but a method for effective prevention of SOS has not been established. METHODS:
      Male Sprague-Dawley rats were treated with cobalt protoporphyrin IX (CoPP) or
      olprinone (OLP), a phosphodiesterase III inhibitor, and hepatic HO-1 expression
      and HO enzymatic activity were determined. Monocrotaline (MCT) was given to rats
      to induce SOS, and blockage of SOS by CoPP or OLP-induced hepatic HO-1 was
      examined in these rats. Zinc protoporphyrin IX (ZnPP), a competitive HO
      inhibitor, was given to MCT-treated rats together with OLP to clarify the
      mechanism of protection against SOS. We also examined if OLP preserved remnant
      liver function after 70% hepatectomy in MCT-treated rats. RESULTS: OLP up
      regulated hepatic HO-1 protein expression and HO enzymatic activity, and
      activated Akt protein. Administration of ZnPP to OLP-treated rats resulted in
      inhibition of HO activity and inactivation of Akt. Induction of HO-1 by
      pretreatment with CoPP led to amelioration of SOS in histologic findings and
      blockage of elevation of serum liver enzymes. Pretreatment with OLP gave a
      similar result and preserved remnant liver function, as indicated by improved
      survival after hepatectomy. ZnPP completely abolished the protective effects of
      OLP. CONCLUSIONS: Protection of the liver from drug-induced injury by prior up
      regulation of HO-1 using OLP may have potential as a therapeutic strategy for
      prevention of SOS.

PMID- 19387322
TI  - Predictors of survival after resection of early hepatocellular carcinoma.
AB  - OBJECTIVE: To identify clinicopathologic factors that predict survival following
      hepatectomy in patients with early hepatocellular carcinoma (HCC). SUMMARY
      BACKGROUND DATA: Although surgical resection of early HCC is thought to be
      associated with a good outcome, factors predictive of prognosis following
      resection of these tumors remain ill-defined. METHODS: The Surveillance,
      Epidemiology, and End Results database was used to identify patients with
      histologically confirmed early HCC (< or =5 cm and no nodal involvement,
      metastases, or major vascular invasion) who underwent surgical resection (not
      ablation or transplantation) between 1988 and 2005. Prognostic factors were
      evaluated using Kaplan-Meier curves and Cox proportional hazards models. RESULTS:
      The study included 788 patients. Median tumor size was 3.2 cm, and 20% of
      patients had tumors < or =2 cm. Most HCC lesions were solitary (74%) and had no
      evidence of vascular invasion (82%). Following surgery, overall median and 5-year
      survival were 45 months and 39%, respectively. After adjusting for demographic
      factors and histological grade, tumor size >2 cm (hazard ratio [HR]: 1.51),
      multifocal tumors (HR: 1.51), and vascular invasion (HR: 1.44) remained
      independent predictors of poor survival (all P < 0.05). Based on these findings,
      a prognostic scoring system was developed that allotted 1 point each for these
      factors. Patients with early HCC could be stratified into 3 distinct prognostic
      groups (median and 5-year survival, respectively): 0 points (70 months, 55%), 1
      point (52 months, 42%), and > or =2 points (24 months, 29%) (P < 0.001).
      CONCLUSIONS: Although early HCC is generally associated with a good prognosis,
      pathologic factors can still be used to stratify patients with respect to
      survival after resection. These data emphasize the importance of pathologic
      staging even in small HCC.

PMID- 19387323
TI  - Should laparoscopic cholecystectomy be practiced in the developing world?: the
      experience of the first training program in Afghanistan.
AB  - OBJECTIVE: We address the controversial issue of whether or not it is wise to
      perform and train laparoscopic cholecystectomy (LC) in a developing nation by
      reviewing the results of the first large series done in Afghanistan. Afghanistan
      has been devastated by 3 decades of war leaving it with deficiencies in training
      programs, medical technologies, and overall medical infrastructure that are among
      the worst in the developing world. METHODS: We retrospectively reviewed 137
      consecutive cholecystectomies, 102 laparoscopic and 35 open, performed by 4
      senior and 3 junior surgeons trained at our hospital in Kabul from July 2005
      until February 2008. Deaths, complications, conversion rate, operative time, and
      hospital length of stay were compared. RESULTS: Unrecognized major operative
      injuries occurred in 4 LC patients, 3 bile leaks, and 1 duodenal perforation,
      although there were no such injuries in the open cholecystectomy group.
      Complication rates were much higher for patients operated on for acute
      cholecystitis for both surgeon groups. Even though junior surgeons converted to
      open cholecystectomy more frequently than senior surgeons, they had a higher
      major complication rate. Hospital length of stay was 28% shorter for the
      laparoscopic group. CONCLUSIONS: The high rate of major unrecognized
      intraoperative complications during LC in our series underscores the difficulties
      inherent in performing and training LC in developing nations. Practical changes
      are suggested to make LC more efficient and safer in a developing world hospital.

PMID- 19387324
TI  - Comparison of the prognostic value of inflammation-based pathologic and
      biochemical criteria in patients undergoing potentially curative resection for
      colorectal cancer.
AB  - OBJECTIVE: To examine interrelationships between the local inflammatory response
      (Klintrup and Jass scores) and the systemic inflammatory response (Glasgow
      prognostic score [GPS]), and compare their prognostic value in patients
      undergoing curative resection for colorectal cancer. BACKGROUND: Both localized
      peritumoral inflammatory cell infiltrate and the host systemic inflammatory
      response are known to have prognostic value in colorectal cancer. However, the
      interrelationships of biochemical and cellular components of the systemic
      inflammatory response and the local inflammatory response are poorly understood.
      METHODS: Retrospective study of 287 patients who underwent surgery between 1997
      and 2004. Data were collected from routine preoperative blood tests. Routine
      pathology specimens were scored according to Jass and Klintrup criteria for
      peritumoral infiltrate. RESULTS: Increased Dukes stage was associated with less
      peritumoral infiltrate (Jass criteria: P < 0.001, Klintrup criteria: P < 0.01).
      Increased modified GPS (mGPS) was associated with increased circulating white
      cell (P < 0.01) and neutrophil (P < 0.01) counts and low lymphocyte counts (P <
      0.01). Increased circulating white cell count was associated with increased
      neutrophil count (P < 0.001) and low-grade peritumoral infiltrate (P < 0.05,
      Klintrup criteria). Jass and Klintrup criteria for peritumoral infiltrate were
      directly associated (P < 0.001). On univariate survival analysis of patients with
      node-negative disease (Dukes A and B), age (P < 0.01), mGPS (P < 0.01),
      neutrophil count (P < 0.05), and Klintrup criteria (P < 0.05) were associated
      with cancer-specific survival. On multivariate survival analysis in node-negative
      disease, the mGPS (hazard ratio: 2.61, 95% CI: 1.27-5.35, P < 0.01) and Klintrup
      criteria (hazard ratio: 6.31, 95% CI: 1.40-28.44, P < 0.05) were independently
      associated with cancer-specific survival. CONCLUSIONS: The results of the present
      study suggest low peritumoral infiltrate (Klintrup criteria) and increased
      systemic inflammation (mGPS criteria) are linked through the cell-mediated immune
      system. Furthermore, both pathologic (Klintrup) and biochemical (mGPS) measures
      of the inflammatory response predict survival after colorectal cancer surgery.

PMID- 19387325
TI  - Effect of body mass index on the outcome of patients with rectal cancer receiving
      curative anterior resection: disparity between the upper and lower rectum.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of body mass index
      (BMI) on local recurrence of primary rectal cancer after open curative sphincter
      saving resection. BACKGROUND: Increasing BMI was reported to be associated with a
      higher likelihood of local recurrence in male patients with rectal cancer.
      However, it remained unclear whether BMI exerts the same effects on local
      recurrence of rectal cancer in the upper and lower rectum. METHODS: Between
      January 1995 and December 2002, we investigated 1873 patients with well
      documented body height and body weight who underwent curative anterior resection
      for primary rectal cancer in a single institution. The patients were assigned to
      4 groups according to their BMI: underweight, normal, overweight, and obese.
      RESULTS: The frequency of local recurrence increased with an increase in the BMI
      in patients with lower rectal cancer. The local recurrence rates were 2.5% (2 of
      79), 6.1% (48 of 782), 9.2% (39 of 424), and 13.8% (9 of 65) in underweight,
      normal, overweight, and obese patients with lower rectal cancer, respectively.
      These results were different from those of patients with upper rectal cancer.
      Independent risk factors for local recurrence in the lower rectal cancer group
      were BMI, resection margin, histologic grade of differentiation, depth of tumor
      invasion, and status of lymph node metastases. In the upper rectal cancer group,
      the depth of tumor invasion and histologic grade of differentiation reached
      statistical significance. CONCLUSIONS: BMI exerted different effects on local
      recurrence of rectal cancer in the upper and lower rectum. Further, more
      aggressive adjuvant and/or neoadjuvant treatments should be considered for
      patients with tumor in the lower rectum and with higher BMI.

PMID- 19387326
TI  - Transanal endoscopic microsurgery versus conventional transanal excision for
      patients with early rectal cancer.
AB  - OBJECTIVE: To compare transanal endoscopic microsurgery (TEMS) with conventional
      transanal excision (TAE) in terms of the quality of resection, local recurrence,
      and survival rates in patients with stage I rectal cancer. BACKGROUND: Although
      TEMS is often considered a superior surgical technique to TAE, it is poorly
      suited for excising tumors in the lower third of the rectum. Such tumors may
      confer a worse prognosis. METHODS: We retrospectively reviewed information on all
      patients with stage pT1 and pT2 rectal adenocarcinoma who underwent local
      excision from 1997 through mid-2006. We excluded patients with node-positive,
      metastatic, recurrent, previously irradiated, or snare-excised tumors. RESULTS:
      Our study included 42 TEMS and 129 TAE patients. We found no significant
      differences in patient characteristics, adjuvant therapy, tumor stage, or adverse
      histopathologic features. In the TAE group, 52 (40%) of tumors were <5 cm from
      the anal verge (AV); in the TEMS group, only 1 (2%) (P = 0.0001). Surgical
      margins were less often positive in the TEMS group (2%) than in the TAE group
      (16%) (P = 0.017). For patients with tumors > or =5 cm from the AV, the estimated
      5-year disease-free survival (DFS) rate was similar between the TEMS group
      (84.1%) and the TAE group (76.1%) (P = 0.651). But within the TAE group, the
      estimated 5-year DFS rate was better for patients with tumors > or =5 cm from the
      AV (76.1%) vs. <5 cm from the AV (60.5%) (P = 0.029). In our multivariate
      analysis, the tumor distance from the anal verge, the resection margin status,
      the T stage, and the use of adjuvant therapy--but not the surgical technique
      (i.e., TEMS or TAE) itself--were independent predictors of local recurrence and
      DFS. CONCLUSIONS: The quality of resection is better with TEMS than with TAE.
      However, the apparently better oncologic outcomes with TEMS can be partly
      explained by case selection of lower-risk tumors of the upper rectum.

PMID- 19387327
TI  - A novel subclassification of pT2 gastric cancers according to the depth of
      muscularis propria invasion: superficial muscularis propria versus deep
      muscularis propria/subserosa.
AB  - PURPOSE: To propose a novel subclassification of pT2 gastric cancers according to
      the depth of muscularis propria (MP) invasion (superficial MP vs. deep
      MP/subserosa [SS]) and to investigate its impact in prognostic assessment.
      SUMMARY BACKGROUND DATA: The major change in the sixth edition of the
      International Union Against Cancer (UICC)/American Joint Committee on Cancer
      (AJCC) TNM classification concerned the pT (primary tumor) category.
      Specifically, pT2 lesions were divided into pT2a (invading the MP) and pT2b
      (invading the SS) to discriminate these intramural locations. However, the value
      of the modification is still debated. METHODS: One thousand two hundred fifty-six
      patients with pT2 cancers classified according to the UICC/AJCC pT staging system
      were reviewed. Among them, 214 (17.0%) were classified as invasion of the
      superficial MP (sMP) or inner circular muscle, 163 (13.0%) as invasion of the
      deep MP (dMP) or outer longitudinal muscle, and 879 (70.0%) as invasion of SS.
      Clinicopathologic features were compared between patients with sMP, dMP, and SS
      invasion. Overall survival rates were compared between the pT2a and pT2b stage
      cancers, according to the UICC/AJCC and the novel pT2 system. Two-step
      multivariate analysis was performed to identify the significantly important
      prognostic factors. RESULTS: There was significant difference in most of the
      clinicopathologic features between sMP and SS cancers. Although, only 5 factors
      (tumor location, tumor size, Borrmann type, metastasis number, and metastasis
      ratio) were significantly different between dMP and SS cancers. In step 1 of the
      multivariate analysis, the UICC/AJCC pT2 system was an independent factor that
      correlated with prognosis, but was substituted by the novel pT2 system in step 2
      of the multivariate analysis. With a certain metastasis ratio of lymph nodes, the
      novel pT2 system discriminated 2 subsets of patients with significantly different
      prognoses, whereas the UICC/AJCC pT2 system did not. CONCLUSIONS: The novel pT2
      staging system, which was subclassified as sMP and dMP/SS cancers, had more
      potential to identify the different prognoses for patients with pT2 gastric
      cancers.

PMID- 19387328
TI  - Post-treatment endoscopic biopsy is a poor-predictor of pathologic response in
      patients undergoing chemoradiation therapy for esophageal cancer.
AB  - PURPOSE: Endoscopic biopsy after chemoradiation therapy (CRT) for esophageal
      cancer has been used to determine response to treatment. We wanted to determine
      if endoscopic biopsy can accurately establish evidence of local pathologic
      complete response (pCR) in patients undergoing CRT. METHODS: We queried a
      prospectively maintained database for patients seen at Memorial Sloan-Kettering
      Cancer Center from 1996 to the present who underwent, (1) CRT for local
      regionally advanced esophageal cancer, (2) post-CRT endoscopic biopsy, and (3)
      esophagectomy. Data points included pathology of post-CRT endoscopy and surgical
      specimens, tumor histology, and survival. Correlations were analyzed by the chi2
      test and one-way analysis of variance. Survival comparisons were assessed using
      the Kaplan-Meier method and log-rank analysis. RESULTS: One hundred fifty-six
      patients were identified. Over 80% of patients received cisplatin-based
      chemotherapy and 5040 cGy of radiation. One hundred eighteen patients had no
      tumor identified on endoscopic biopsy. A negative biopsy at endoscopy was a poor
      predictor of pCR (negative predictive value: 31%), with 69% having local disease
      at esophagectomy. A positive biopsy was predictive of residual disease (positive
      predictive value: 95%). Negative endoscopic biopsy better predicted a pCR for
      squamous cell carcinomas versus adenocarcinomas (P[r] < 0.001). Nodal status of
      surgical specimens was not correlated with post-treatment endoscopic findings.
      Survival was equivalent after surgery in patients with a negative endoscopic
      biopsy versus patients with positive pathology. CONCLUSION: A negative endoscopic
      biopsy is not a useful predictor of a pCR after CRT, final nodal status, or
      overall survival.

PMID- 19387329
TI  - Validation study of radio-guided sentinel lymph node navigation in esophageal
      cancer.
AB  - BACKGROUND: Radio-guided detection of sentinel lymph nodes (SLN) has been used to
      predict regional lymph node metastasis in patients with melanoma and breast
      cancer. However, the validity of the SLN hypothesis is still controversial for
      esophageal cancer. The aim of this study is to evaluate the feasibility and
      accuracy of radio-guided SLN mapping for esophageal cancer. METHODS: Seventy-five
      consecutive patients who were diagnosed preoperatively with T1N0M0 or T2N0M0
      primary esophageal cancer were enrolled. Endoscopic injection of technetium-99m
      tin colloid was performed before surgery and radioactive SLNs were identified
      with preoperative lymphoscintigraphy and gamma probe. Standard radical
      esophagectomy with lymphadenectomy was performed in all patients and all resected
      nodes were evaluated by routine pathologic examination. RESULTS: SLNs were
      identified successfully in 71 (95%) of 75 patients. The mean number of identified
      SLNs per case was 4.7. Twenty-nine (88%) of 33 cases with lymph node metastasis
      showed positive SLNs. The diagnostic accuracy based on SLN status was 94%
      (67/71). Distribution of identified SLNs was widely spread from the cervical to
      abdominal areas. CONCLUSIONS: This study reveals that radio-guided SLN mapping is
      an accurate diagnostic procedure for detecting lymph node metastasis in patients
      with early-stage esophageal cancer.

PMID- 19387331
TI  - Neuromuscular electrical stimulation reduces skeletal muscle protein degradation
      and stimulates insulin-like growth factors in an age- and current-dependent
      manner: a randomized, controlled clinical trial in major abdominal surgical
      patients.
AB  - OBJECTIVE: To investigate the effect of neuromuscular electrical stimulation
      (NMES) on skeletal muscle metabolism after major abdominal surgery. SUMMARY
      BACKGROUND DATA: Protein catabolism associated with surgical interventions leads
      to reduced muscle strength, increased clinical complications and prolonged
      convalescence. Immobilization is suggested as a major stimulus for muscle
      wasting. This study investigates the potency of NMES on skeletal muscle growth
      factors and degradation processes in surgical patients. METHODS: This observer
      blind study included 26 patients after major abdominal surgery mainly due to
      cancer aged 60 +/- 10 years. Starting on the first postoperative day, 1 randomly
      assigned thigh of each patient was treated on 4 consecutive days with NMES,
      whereas the other leg was used as sham-stimulated control. Thereafter, muscle
      biopsies from both legs were performed. Differences in mRNA level, protein
      expression, and enzyme activity between legs were analyzed by cross-over analysis
      of variance (Clinical Trial Registration Number: NCT00635440). RESULTS: NMES
      significantly increased total RNA content and total sarcoplasmatic protein
      content. NMES significantly reduced ubiquitin-conjugated sarcoplasmatic proteins
      and proteasome activity. The mechano growth factor mRNA level correlated
      positively with the applied current and negatively with the body mass index of
      the patients. The increase in insulin like growth factor-1Ea mRNA after NMES
      correlated negatively with the age of the patients. CONCLUSIONS: This study shows
      that NMES significantly increases total RNA content and reduces protein
      degradation in postoperative patients. Moreover, the induction of growth factors
      by NMES reveals dependency on body mass index, age, and applied current. We
      conclude that NMES is a useful clinical tool to reduce protein catabolism in
      postoperative patients.

PMID- 19387332
TI  - Real time intraoperative confocal laser microscopy-guided surgery.
AB  - OBJECTIVE: To assess the potential utility of in vivo histologic surface and
      subsurface imaging in real-time using the Optiscan confocal laser microscope to
      detect diseased tissue at the time of surgery. SUMMARY BACKGROUND DATA: The goal
      of surgical treatment of diseases such as cancer is complete microscopic
      resection of diseased tissue; however, current methods for the assessment of
      extent of disease at the time of surgery are inadequate. METHODS: We assessed the
      potential of the Optiscan confocal laser microscope, a new device developed for
      real-time in vivo histologic surface and subsurface imaging during surgery.
      RESULTS: Intravenous Fluorescein Sodium contrast enabled visualization of
      cellular and architectural morphology of intra-abdominal organs with
      magnification equivalent to light microscopy and enabled differentiation between
      normal organs and disease. CONCLUSIONS: Real time intraoperative confocal
      microscopy has significant potential application in detecting disease, and
      influencing decision-making at the time of surgery.

PMID- 19387330
TI  - Influence of acute epinephrine infusion on endotoxin-induced parameters of heart
      rate variability: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether the acute anti-inflammatory influence of
      epinephrine (EPI) extends to changes in heart rate variability (HRV) induced by
      the prototypical inflammatory stimulus, endotoxin (lipopolysaccharide [LPS]).
      SUMMARY BACKGROUND DATA: HRV reflects fluctuating cardiac autonomic inputs and is
      acutely reduced during the systemic inflammation induced by LPS as well as during
      severe critical illnesses such as sepsis and traumatic injury. While EPI may
      diminish proinflammatory cytokine release, it is unknown whether this net anti
      inflammatory activity extends to HRV. METHODS: Healthy volunteers (n = 17) were
      randomized to either saline + LPS (2 ng/kg) or LPS + antecedent EPI infusion (30
      ng/kg/min) from -3 to 6 hours relative to LPS. HRV and blood samples were
      obtained before EPI and LPS as well as hourly afterward. Plasma cytokines were
      measured by ELISA. Statistical analysis was by repeated measures analysis of
      variance. This study was registered at Clinicaltrials.gov and is listed under the
      following ID number: NCT00753402. RESULTS: LPS acutely influenced all measured
      parameters of HRV including standard deviation of the average beat to beat
      intervals over a 5-minute period, percentage of interval differences of
      successive interbeat intervals greater than 50 milliseconds and square root of
      the mean squared differences, high frequency (HF), low frequency, low
      frequency/HF, and very low frequency (all P < 0.01). EPI infusion reduced the
      inflammatory cytokine response to LPS as measured by decreased TNFalpha, IL-6,
      and IL-8 (P < 0.01). Relative to the saline + LPS group, antecedent EPI infusion
      was associated with further reductions in parameters of HRV measuring
      vagal/parasympathetic activity including, percentage of interval differences of
      successive interbeat intervals greater than 50 milliseconds, square root of the
      mean squared differences, and HF (P < 0.05). CONCLUSION: Prior EPI exposure
      exerts anti-inflammatory influences but also may reduce vagus nerve activity.
      Hence, acute EPI administration may be protective against early inflammatory
      challenges but diminish vagal nerve responsiveness to subsequent stimuli.

PMID- 19387333
TI  - The perioperative period is an underutilized window of therapeutic opportunity in
      patients with colorectal cancer.
AB  - OBJECTIVE: In this review, we address the underlying mechanisms by which surgery
      augments metastases outgrowth and how these insights can be used to develop
      perioperative therapeutic strategies for prevention of tumor recurrence. SUMMARY
      BACKGROUND DATA: Surgical removal of the primary tumor provides the best chance
      of long-term disease-free survival for patients with colorectal cancer (CRC).
      Unfortunately, a significant part of CRC patients will develop metastases, even
      after successful resection of the primary tumor. Paradoxically, it is now
      becoming clear that surgery itself contributes to development of both local
      recurrences and distant metastases. METHODS: Data for this review were identified
      by searches of PubMed and references from relevant articles using the search
      terms "surgery," "CRC," and "metastases." RESULTS: Surgical trauma and
      concomitant wound-healing processes induce local and systemic changes, including
      impairment of tissue integrity and production of inflammatory mediators and
      angiogenic factors. This can lead to immune suppression and enhanced growth or
      adhesion of tumor cells, all of which increase the chance of exfoliated tumor
      cells developing into secondary malignancies. CONCLUSIONS: Because surgery
      remains the appropriate and necessary means of treatment for most CRC patients,
      new adjuvant therapeutic strategies that prevent tumor recurrence after surgery
      need to be explored since the perioperative therapeutic window of opportunity
      offers promising means of improving patient outcome but is unfortunately
      underutilized.

PMID- 19387334
TI  - Operative experience of residents in US general surgery programs: a gap between
      expectation and experience.
AB  - OBJECTIVE: The purpose of the study was to identify a group of operations which
      general surgery residency program directors believed residents should be
      competent to perform by the end of 5 years of training and then ascertain actual
      resident experience with these procedures during their training. SUMMARY
      BACKGROUND DATA: There is concern about the adequacy of training of general
      surgeons in the United States. The American Board of Surgery and the Association
      of Program Directors in Surgery undertook a study to determine what operative
      procedures residency program directors consider to be essential to the practice
      of general surgery and then we measured the actual operative experience of
      graduating residents in those procedures, as reported to the Residency Review
      Committee for Surgery (RRC). METHODS: An electronic survey was sent to residency
      program directors at the 254 general surgery programs in the US accredited by the
      RRC as of spring 2006. The program directors were presented with a list of 300
      types of operations. Program directors graded the 300 procedures "A," "B," or "C"
      using the following criteria: A--graduating general surgery residents should be
      competent to perform the procedure independently; B--graduating residents should
      be familiar with the procedure, but not necessarily competent to perform it; and
      C--graduating residents neither need to be familiar with nor competent to perform
      the procedure. After ballots were tallied, the actual resident operative
      experience reported to the RRC by all residents finishing general surgery
      training in June 2005 was reviewed. RESULTS: One hundred twenty-one of the 300
      operations were considered A level procedures by a majority of program directors
      (PDs). Graduating 2005 US residents (n = 1022) performed only 18 of the 121 A
      procedures, an average of more than 10 times during residency; 83 of 121
      procedures were performed on an average less than 5 times and 31 procedures less
      than once. For 63 of the 121 procedures, the mode (most commonly reported)
      experience was 0. In addition, there was significant variation between residents
      in operative experience for specific procedures. In virtually all cases, the mean
      reported experience exceeded the mode, suggesting that the mean is a poor measure
      of typical experience. CONCLUSIONS: These data pose important problems for
      surgical educators. Methods will have to be developed to allow surgeons to reach
      a basic level of competence in procedures which they are likely to experience
      only rarely during residency. Even for more commonly performed procedures, the
      numbers of repetitions are not very robust, stressing the need to determine
      objectively whether residents are actually achieving basic competency in these
      operations. Finally, the large variations in experience between individuals in
      our residency system need to be explored, understood, and remedied.

PMID- 19387335
TI  - The impact of surgeon specialization on patient mortality: examination of a
      continuous Herfindahl-Hirschman index.
AB  - OBJECTIVE: To examine the effect of surgeon specialization on patient outcomes,
      controlling for volume. BACKGROUND: There is great interest in the degree to
      which surgical specialization affects outcomes, particularly considering drives
      to measure and reward quality in healthcare. Although surgical specialization has
      been previously analyzed with respect to outcomes, most studies have treated it
      as a dichotomous variable based on academic credentials. We treat it here as a
      continuous variable defined quantitatively by procedural diversity. METHODS: We
      used 2002 to 2005 patient data from the National Surgical Quality Improvement
      Program for the Department of Surgery, Barnes Jewish Hospital, St. Louis,
      Missouri. To quantitate procedural specialization, Herfindahl-Hirschman indices
      for surgeons were calculated using billing codes. These indices were calculated
      according to 3 different levels of procedural aggregation. Using conditional
      logit models, we examined the relationship between these indices and 30-day
      postoperative mortality rates. RESULTS: Surgeon specialization was inversely
      related to mortality rates after adjusting for case volume when indices were
      calculated using medium procedural aggregation (odds ratio for mortality = 0.580
      per 0.1 unit Herfindahl increase; P = 0.025) or low aggregation (odds ratio for
      mortality = 0.510 per 0.1 unit Herfindahl increase; P = 0.015). No relationship
      was observed at the high level of aggregation. CONCLUSIONS: The procedural
      concentration component of surgical specialization is correlated with improved
      mortality rates independently of case volume. However, how broadly or narrowly
      "specialization" is defined has an impact on this relationship.

PMID- 19387336
TI  - Interactive spaced education to assess and improve knowledge of clinical practice
      guidelines: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether Interactive Spaced Education (ISE) is an
      effective and acceptable form of graduate and continuing medical education
      (GME/CME), using clinical practice guideline (CPG) education as an experimental
      system. SUMMARY BACKGROUND DATA: ISE is a novel form of online education, which
      combines the pedagogical merits of the spacing and testing effects. Its efficacy
      for GME and CME is not known. METHODS: One-hundred sixty urologists and 320
      urology residents were randomized to 1 of 2 cohorts. We developed and validated
      48 ISE items (questions and answers) on 5 urology CPGs (hematuria and priapism
      [HP]; staghorn calculi, infertility, and antibiotic use [SIA]). Physicians were
      sent 3 emails a week, each containing 2 questions. Content was repeated 3 times
      over 20 weeks. Cohort A physicians received the 3-cycle ISE course on HP, with 24
      control items on SIA in cycle 3. Cohort B physicians received the 3-cycle ISE
      course on SIA, with 24 control items on HP in cycle 3. RESULTS: The ISE program
      was completed by 71% urologists and 83% residents. Cohort A scores on HP
      increased from mean 44.9% in cycle 1% to 75.7% in cycle 3, a 57% relative
      increase compared with controls (P < 0.001; Cohen effect size, 2.2). Similarly,
      cohort B scores on SIA increased from 45.2% in cycle 1% to 69.5% in cycle 3, a
      56% relative increase compared with controls (P < 0.001; effect size, 2.2).
      Eighty-four percent of all participants requested to enroll in further ISE
      programs. CONCLUSIONS: ISE is an effective and well-accepted form of GME and CME
      and is a promising new methodology to improve CPG knowledge.

PMID- 19387338
TI  - New cytotoxic rosamine derivatives selectively accumulate in the mitochondria of
      cancer cells.
AB  - Conventional cytotoxic anticancer drugs that target all rapidly dividing cells
      are nonselective in their mechanism of action, because they disrupt essential
      components that are crucial to both malignant and proliferating normal cells.
      Instead, targeting cellular functions that are distinctly different between
      normal and cancer cells may provide a basis for selective killing of tumor cells.
      One such strategy that is still largely unexplored is to utilize the relatively
      higher negative mitochondrial membrane potential in carcinoma cells compared with
      adjacent normal epithelial cells to enhance accumulation and retention of
      cytotoxic lipophilic cations in the former. In this study, the anticancer
      activities of a new class of rosamines with cyclic amine substituents and their
      structure-activity relationships were investigated. From an in-vitro cell growth
      inhibition assay, 14 of the rosamines inhibited the growth of human leukemia HL
      60 cells by 50% at micromolar or lower concentrations. Derivatives containing
      hydrophilic substituents had less potent activity, whereas aryl substitution at
      the meso position conferred extra activity with thiofuran and para-iodo aryl
      substitutions being the most potent. In addition, both compounds were at least 10
      fold more cytotoxic than rhodamine 123 against a panel of cell lines of different
      tissue origin and similar to rhodamine 123, exhibited more cytotoxicity against
      cancer cells compared with immortalized normal epithelial cells of the same organ
      type. In subsequent experiments, the para-iodo aryl substituted rosamine was
      found to localize exclusively within the mitochondria and induced apoptosis as
      the major mode of cell death. Our results suggest that these compounds offer
      potential for the design of mitochondria-targeting agents that either directly
      kill or deliver cytotoxic drugs to selectively kill cancer cells.

PMID- 19387337
TI  - Prevention of pancreatic cancer by the beta-blocker propranolol.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer
      deaths and is unresponsive to existing therapy. Smoking and alcohol-induced
      pancreatitis are among the risk factors for PDAC. We have previously reported
      that beta-adrenergic receptors (beta-ARs) stimulate the proliferation and
      migration of human PDAC cells in vitro by cAMP-dependent signaling and that the
      nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      activates this pathway directly in vitro while additionally stimulating the
      release of noradrenaline/adrenaline by binding to alpha7 nicotinic acetylcholine
      receptors (alpha7 nAChR) in hamsters. In this study, we have tested the
      hypothesis that the beta-AR antagonist propranolol prevents the development of
      PDAC induced in hamsters with ethanol-induced pancreatitis by NNK. We found that
      propranolol had strong cancer preventive effects in this animal model. Western
      blots of pancreatic duct cells and PDAC cells harvested by laser capture
      microscopy showed significant upregulation of the alpha7 nAChR associated with
      significant inductions of p-CREB, p-ERK1/2, and increases in epidermal growth
      factor and vascular endothelial growth factor in PDAC cells of hamsters not
      treated with propranolol. These effects were reversed by treatment with
      propranolol. Our data suggest that propranolol may prevent the development of
      PDAC by blocking cAMP-dependent intracellular signaling, cAMP-dependent release
      of epidermal growth factor, and PKA-dependent release of vascular endothelial
      growth factor while additionally downregulating the alpha7 nAChR by inhibiting
      cAMP-mediated subunit assembly. We conclude that increased cAMP signaling is an
      important factor that drives the development and progression of PDAC and that the
      inhibition of cAMP formation is a promising new target for the prevention and
      adjuvant therapy of PDAC.

PMID- 19387339
TI  - Clinical assessment of hemodynamically unstable patients.
AB  - PURPOSE OF REVIEW: Clinical examination of hemodynamically unstable patients
      provides timely, low-risk, and potentially useful diagnostic and prognostic
      information. This review will examine the evidence behind the use of clinical
      examination findings to drive treatment decisions and predict outcomes in
      patients with hemodynamic instability. An additional goal of the review is to
      place the use of clinical examination in context of more invasive techniques to
      diagnose and treat hemodynamically unstable patients. RECENT FINDINGS: The
      development of novel diagnostic tests based on recently developed technology has
      focused attention on methods to determine when a test should enter routine
      clinical use. The widespread incorporation of pulmonary artery catheterization
      into clinical practice prior to formal evaluation of its ability to improve
      outcomes highlights the importance of properly evaluating diagnostic tests in
      critically ill patients. Formal evaluation of clinical examination as a
      diagnostic test will allow better understanding of its role in the hemodynamic
      evaluation of critically ill patients. SUMMARY: Clinical examination remains an
      important initial step in the diagnosis and risk stratification of patients.
      Despite limitations of current techniques, the availability, low risk, and
      ability to perform repetitive tests ensure that clinical examination of the
      hemodynamically unstable patient will continue to be a useful tool for the
      intensivist until more useful tests are validated in this patient population.

PMID- 19387340
TI  - Current use of the pulmonary artery catheter.
AB  - PURPOSE OF REVIEW: The pulmonary artery catheter is one of the most scrutinized
      monitors used in intensive care today. Pulmonary artery catheter use is declining
      due to limited demonstrated beneficial outcomes and the advancement of less
      invasive monitoring. This study discusses the current use of the pulmonary artery
      catheter and problems associated with its use including inaccuracy of
      measurements and data interpretation, inappropriately applied therapeutic
      interventions, inappropriate delays in applying interventions, and inappropriate
      patient selection. RECENT FINDINGS: This overview presents current controversies
      surrounding the pulmonary artery catheter. It also discusses commonly used
      monitors and their lack of demonstrated benefits. In addition, data show that
      intensivists do not have sufficient knowledge to effectively use the pulmonary
      artery catheter. When utilized in a timely appropriate manner, pulmonary artery
      catheter monitoring may benefit a selected patient population. SUMMARY: In
      summary, the pulmonary artery catheter monitor continues to be used for intensive
      care patients. To date, no single monitor is associated with an abundance of
      clear outcome benefits. There are some clinical data showing that the pulmonary
      artery catheter may still be useful when applied to the right patient population
      using appropriately timed therapies.

PMID- 19387341
TI  - Multiple sclerosis and the major histocompatibility complex.
AB  - PURPOSE OF REVIEW: Multiple sclerosis (MS) is the most common neurological
      disease affecting young adults. The cause is unknown, but detailed
      epidemiological and genetic studies have shown a clear inherited component. We
      review here some of the recent findings of MS genetics with a particular focus on
      genes of the major histocompatibility complex (MHC). RECENT FINDINGS: Recent
      studies add further complexity to the role of the MHC in MS. Reported MHC
      associations are complex, involving haplotypes rather than single alleles and may
      involve epigenetic mechanisms and other modulators of gene expression. MHC class
      II haplotypes display a hierarchy of risks, including protective effects and
      epistatic interactions, which together dwarf any non-MHC genetic effect. Genes in
      the MHC region have been shown to influence disease severity, display parent-of
      origin effects and interact with a major environmental candidate for MS, vitamin
      D. SUMMARY: The MHC class II association with MS is not as straightforward as
      previously thought. A complete understanding of the epistatic interactions and
      epigenetic features of this region will be important to understand disease
      pathogenesis and likely aid the discovery of new therapeutics.

PMID- 19387342
TI  - Pathogenesis of septic encephalopathy.
AB  - PURPOSE OF REVIEW: Septic encephalopathy is a frequent complication in severe
      sepsis, the pathogenesis and mechanisms of which are not fully understood. Here,
      we review recent advances in our understanding of septic encephalopathy, from
      molecular mechanisms to behavioral alterations, from diagnostic tools to
      potential therapeutic agents. RECENT FINDINGS: Recent insights into septic
      encephalopathy include: microcirculatory failure precedes changes in evoked
      potential responses; blood-brain barrier alteration is prevented by reducing
      intercellular adhesion molecule expression and pericyte detachment; reducing
      infiltration of CD68 macrophages and inhibiting complement activation alleviates
      neuroinflammation in septic encephalopathy; and reducing mitochondrial
      dysfunction and inducible nitric oxide synthase expression can restore altered
      brain function. In addition, other factors such as the circulating levels of
      growth hormone are independent predictors for mortality and correlate with the
      severity of sepsis. Similar to humans, septic rats present recognition memory
      impairment and depressive-like symptoms but not anxiety-like behavior and will
      serve as efficient models to study the underlying mechanisms of septic
      encephalopathy. SUMMARY: Septic encephalopathy is a dynamic disease caused by a
      complex network of systems and pathways going awry. More insights into the
      pathogenesis of septic encephalopathy are expected to lead to new cellular and
      molecular targets, which in turn will permit design of specific septic
      encephalopathy-alleviating drugs and prevent its negative influence on survival.

PMID- 19387343
TI  - Nocardia keratitis.
AB  - PURPOSE OF REVIEW: Nocardia keratitis is a rarity in most parts of the world. If
      the diagnosis is timely, and appropriate treatment started, then the visual
      outcome is good. The purpose of this review is to discuss the recently published
      literature in relation to the epidemiology, cause, diagnosis, and therapy of
      Nocardia keratitis. RECENT FINDINGS: The incidence of Nocardia keratitis,
      although not well established, appears to be increasing with new species
      identified with newer molecular methods. The different species causing keratitis
      are Nocardia. arthritidis, N. neocaledoniensis, N. asiatica, N. asteroids type
      IV, N. brasiliensis, N. pseudobrasiliensis, N. cyriacigeorgica, N. farcinica, N.
      otitidiscaviarum, and N. transvalensis. Current therapies with fortified amikacin
      and newer fluoroquinolones are effective, provided the diagnosis has been made in
      good time. Ongoing research toward rapid diagnosis using various molecular
      techniques seems to be promising. Diagnostic microbiology laboratories need to be
      familiar with these organisms especially in endemic areas, and it is important
      for the clinician to notify the suspicion of such cases. SUMMARY: The current
      recommended treatment is amikacin, and with appropriate therapy, Nocardia
      keratitis resolves with scarring, with or without vascularization, resulting in
      good visual outcome.

PMID- 19387344
TI  - Comparative effectiveness.
AB  - PURPOSE OF REVIEW: To familiarize the clinician with the concept of comparative
      effectiveness. RECENT FINDINGS: Recent data support the concept that utility
      analysis is the quality-of-life instrument best able to perform comparative
      effectiveness analyses. The use of time tradeoff utilities for comparative
      effectiveness analyses in interventions across diverse specialties of medicine
      can be undertaken with both excellent reliability and superior construct
      validity. SUMMARY: Physicians should familiarize themselves with quality-of-life
      instruments that can be used to assess the comparative effectiveness of
      healthcare interventions. Rather than delegating comparative effectiveness to
      others, physicians must become involved in creating and implementing comparative
      effectiveness standards. Physician involvement is crucial for the best interests
      of patients, as physicians most intimately understand the complexities and
      nuances associated with healthcare interventions.

PMID- 19387345
TI  - Advanced airway management.
AB  - PURPOSE OF REVIEW: Advanced airway management in children can be challenging, and
      the potential for morbidity following failed attempts is high. RECENT FINDINGS:
      Supraglottic rescue devices, including the laryngeal mask airway, esophageal
      tracheal combination tube, and laryngeal tube have been shown to be suitable
      ventilation strategies following failed intubation and in arrest scenarios. In
      addition, a newly developed reversal agent for rocuronium is being investigated
      as a means of limiting the duration of neuromuscular blockade following rapid
      sequence induction. Finally, the advent of video laryngoscopy has been shown to
      have advantages over traditional direct laryngoscopy, in terms of both patient
      care and training. SUMMARY: Pediatric providers are encouraged to develop
      familiarity with emerging rescue ventilation devices, as well as recent advances
      in the practice of rapid sequence induction and laryngoscopy.

PMID- 19387346
TI  - Advances in treating acute asthma exacerbations in children.
AB  - PURPOSE OF REVIEW: Asthma continues to be a major chronic disease in children,
      and acute asthma exacerbations are common. Although the basic therapy of asthma
      exacerbations has not changed, recent studies have demonstrated improved outcomes
      with different modes of delivery of medications, improved patients' self
      management of their asthma, and recognition of risk factors for severe
      exacerbations. RECENT FINDINGS: Recent studies in children have shown that
      written action plans based on symptom recognition are more effective than action
      plans based on peak expiratory flows. Bronchodilator administration by metered
      dose inhaler is becoming the preferred therapy for treating mild-to-moderate
      asthma exacerbations in the emergency department, but nebulizers may still have a
      role in home and inpatient asthma management. High-dose inhaled corticosteroids
      may be as effective as oral corticosteroids for acute asthma exacerbations. A
      novel treatment strategy has titrated combination therapy with budesonide and
      formoterol for both maintenance and relief of symptoms. Lastly, the contributions
      of obesity and genetic variation to severe asthma exacerbations are becoming
      known, and noninvasive positive pressure ventilation has become an option for
      patients in severe asthma exacerbations. SUMMARY: Improvements in management
      strategies can significantly improve outcomes in children with asthma.

PMID- 19387347
TI  - Youth Internet use: risks and opportunities.
AB  - PURPOSE OF REVIEW: The Internet has become all pervasive in the lives of young
      people and this paper will review studies that examine the risks and
      opportunities that it affords. We will examine research that investigates the
      more negative aspects of youth online behavior such as addiction as well as
      online risks such as harassment/cyber bullying and sexual solicitation. In
      addition, positive aspects of Internet use such as its potential for learning and
      enhancing social relations as well as delivering health interventions will be
      examined. RECENT FINDINGS: The results show that online risks such as addiction,
      cyber bullying, and sexual solicitation are associated with negative consequences
      for youth. It is important to note that not all children are equally susceptible
      and more research is necessary to identify the youth most at risk as well as to
      develop effective interventions. The Internet can also provide benefits in the
      areas of cognitive, social, and physical development, and can also be used to
      deliver treatment interventions. SUMMARY: The Internet represents both risks and
      opportunities for young people. To protect youth who are at risk for online
      addiction, bullying, and solicitation, we need more research to understand which
      youth may be most susceptible and to develop targeted interventions to protect
      them. The Internet also has many positive aspects and can be used to enhance
      youth learning and empowerment; although it is a tremendous health resource and
      can be used to cheaply deliver interventions, we need to understand how to better
      implement them to enhance their effectiveness.

PMID- 19387348
TI  - Thyroid disorders in mental patients.
AB  - PURPOSE OF REVIEW: Thyroid hormones play important roles in brain development and
      function. Recent findings concerning thyroid hormones secretion, transport, and
      metabolism in the brain have provided a better understanding of the role of
      thyroid hormones in mental disorders. RECENT FINDINGS: The intracellular actions
      of thyroid hormones in brain are determined by a complex of factors, including
      circulating concentrations of thyroid hormones, availability of free hormone,
      activity of thyroid hormone transporters and deiodinase enzymes, and activity of
      thyroid hormone receptors. Individual genetic variations and mutations of thyroid
      axis-related proteins influence thyroid hormone activity in the brain and
      contribute to the presentation of mental disorders, as well as to response to
      psychiatric treatments. SUMMARY: Consideration of molecular mechanism related to
      genetic alterations in thyroid hormone transport into the neuron, intracellular
      thyroid hormone metabolism in the brain, as well as polymorphism in thyroid
      hormone receptors, opens new venues for better understanding of thyroid hormone
      effects in the brain as well as for finding genetic markers and new targets for
      the treatment of mental disorders.

PMID- 19387349
TI  - Medical thoracoscopy.
AB  - PURPOSE OF REVIEW: The technique and clinical applications of medical
      thoracoscopy have substantially evolved in the last few decades. The recent
      development of a semirigid thoracoscope, which is handled similarly to a
      bronchoscope, has made this procedure more attractive to pulmonologists. We will
      review the latest data on clinical applications, recently developed techniques,
      and safety of medical thoracoscopy, focusing mainly on its role in thoracic
      malignancies. RECENT FINDINGS: Recent data confirm the high diagnostic yield of
      medical thoracoscopy - both with rigid and semirigid instruments - in detecting
      pleural metastases and determining the origin of pleural effusions. The degree of
      pleural adhesions found during thoracoscopy has been proposed by some authors as
      a prognostic factor for survival in patients with malignant pleural effusion. A
      large prospective multicenter study has established the safety of talc poudrage
      with large-particle talc, showing no cases of acute respiratory distress
      syndrome. SUMMARY: Medical thoracoscopy is an excellent tool to establish
      diagnosis in patients with exudative pleural effusion of unclear origin. It is
      highly valuable in clarifying the origin of pleural effusions in patients with
      lung cancer, as the presence of a malignant pleural effusion is associated with
      poor survival and precludes the possibility of treatment with curative intention.
      Pleurodesis with talc poudrage is efficacious and well tolerated, especially with
      the use of large-particle talc.

PMID- 19387350
TI  - Animal models of malignant pleural effusion.
AB  - PURPOSE OF REVIEW: Malignant pleural effusion (MPE) poses a common and
      significant clinical problem. Its pathogenesis is poorly understood and
      therapeutic options are limited. Herein are summarized animal models of MPE and
      their contributions in unveiling new aspects of the pathobiology of the
      condition. RECENT FINDINGS: In recent years, different groups have developed
      novel models of MPE, including a genetic mouse model of spontaneous mesothelioma
      development, a model of adenocarcinoma-induced MPE in immunocompetent mice, as
      well as models of human cancer-induced MPE in immunocompromised animals, all
      relevant to the human condition to a different extent. Work using these models
      has yielded novel insights into the pathogenesis of mesothelioma as well as into
      the mechanisms of intrapleural malignant effusion accumulation and tumor
      dissemination. The data produced underline the significance of tumor-associated
      inflammation, angiogenesis, and vascular hyperpermeability in the pathogenesis of
      MPE. SUMMARY: In the past few years, novel approaches to induce experimental MPE
      have yielded new insights into its pathogenesis and have identified possible
      therapeutic targets to block pleural fluid exudation induced by primary and
      metastatic cancer cells in the pleural space.

PMID- 19387351
TI  - Ventilator-associated infection.
AB  - PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is the most serious and
      controversial of the infections of the critically ill patient. The accuracy of
      standard methods of diagnosis remains under constant scrutiny, and at the same
      time there is increasing debate about whether it is a preventable disease. This
      review focuses on the pathophysiology of respiratory tract infection in the
      ventilated patient, and how the latest advances have grown from our current
      understanding of its pathogenesis. RECENT FINDINGS: Data from many recent
      investigations have focused on the role of proximal airway infection, ventilator
      associated tracheobronchitis (VAT), in respiratory tract infection. The goals of
      recent trials include reducing the morbidity associated with the progression of
      airway colonization to VAT or with the progression of VAT to VAP. Continuous
      subglottic secretion suctioning, innovative types of endotracheal tubes and
      targeted therapy for VAT in recent investigations have shown promise in improving
      clinical outcomes in the critically ill patient. However, even with diligent
      attention to all the modifiable risk factors for respiratory infection, complete
      elimination of VAT and VAP remains unlikely. As long as a patient requires an
      endotracheal tube that disturbs airway integrity, host defenses will be impaired,
      and resistant virulent organisms that result from our liberal use of systemic
      antibiotics will continue to challenge critical care specialists. SUMMARY: This
      review will focus on: the current understanding of the pathogenesis of VAT and
      VAP, modifiable risk factors and new approaches to treatment, and bacterial
      resistance challenges.

PMID- 19387352
TI  - Relations of serum MMP-9 and TIMP-1 levels to left ventricular measures and
      cardiovascular risk factors: a population-based study.
AB  - BACKGROUND: Extracellular matrix remodeling is a hallmark of pathological left
      ventricular (LV) hypertrophy and heart failure. This process is tightly
      controlled by the degrading matrix metalloproteinases (MMPs) and their tissue
      inhibitors (TIMPs). We hypothesized that circulating MMP-9 and TIMP-1 levels are
      altered already in persons with the signs of LV remodeling that forego clinical
      heart failure. DESIGN: Cross-sectional study in the Prospective Investigation of
      the Vasculature in Uppsala Seniors, a community-based cohort of 891 70-year-old
      men and women free from valvular disease, heart failure, and myocardial
      infarction. METHODS: We examined relations of serum MMP-9 and TIMP-1 to
      echocardiographic LV geometry and function. All models were adjusted for sex,
      height, intra-arterial systolic and diastolic blood pressures, antihypertensive
      medication use, and serum freezer time. RESULTS: Serum TIMP-1 was positively
      related to LV mass and wall thickness (r=0.15, P<0.0001 and r=0.16, P<0.0001,
      respectively), with a 32 g higher LV mass and 2.2 mm thicker walls in the fourth
      compared with the first quartile of serum TIMP-1. Serum TIMP-1 was also inversely
      related to LV ejection fraction (r=-0.10, P=0.009), but not to LV dimension or
      diastolic function indices. Serum MMP-9 was only weakly related to LV wall
      thickness and isovolumic relaxation time (r=0.08, P=0.04 and r=-0.08, P=0.04).
      CONCLUSION: In this large population-based sample, serum TIMP-1 levels were
      related to LV mass, wall thickness, and inversely to systolic function. This may
      imply that extracellular matrix remodeling is involved already in the earliest
      stages of the process leading to heart failure.

PMID- 19387353
TI  - Association of C-reactive protein and HIV infection with acute myocardial
      infarction.
AB  - OBJECTIVE: To investigate whether elevated C-reactive protein (CRP) levels and
      HIV infection are independently associated with acute myocardial infarction (AMI)
      among patients receiving care in a large US health care system. METHODS: Analyses
      included patients receiving care in the Partners HealthCare System between
      January 1997 and December 2006, with a most recent CRP less than 3 years and more
      than 1 week before AMI. Over this period, 70,357 (487 HIV and 69,870 non-HIV)
      patients met these criteria, from the background population of 1,648,687 patients
      followed in the system. We included both CRP and high-sensitivity CRP and defined
      elevated CRP based on the normal range of the assay used. We used multivariate
      logistic regression analysis to test the association of elevated CRP and HIV with
      AMI after adjustment for demographic and other cardiovascular covariates,
      including hypertension, diabetes, and dyslipidemia. RESULTS: In univariate
      analyses, elevated CRP and HIV were each significantly associated with AMI [odds
      ratio (OR) 2.51; 95% confidence interval (CI) 2.27 to 2.78; P < 0.0001 for
      elevated CRP and OR 2.07; 95% CI 1.31 to 3.10; P = 0.001 for HIV]. In a combined
      model including CRP category and HIV status, elevated CRP (OR 2.50; 95% CI 2.26
      to 2.77; P < 0.0001) and HIV (OR 1.74; 95% CI 1.10 to 2.61; P = 0.01) were both
      independently associated with AMI. In a fully adjusted model controlling for age,
      sex, race, hypertension, diabetes, and dyslipidemia, both elevated CRP (OR 2.13;
      95% CI 1.92 to 2.37; P < 0.0001) and HIV (OR 1.93; 95% CI 1.21 to 2.93; P =
      0.004) remained independently associated with AMI. Compared with patients with
      normal CRP and without HIV, the OR for AMI was increased more than 4-fold among
      patients with HIV and elevated CRP. CONCLUSIONS: Elevated CRP and HIV are
      independently associated with increased AMI risk, and patients with HIV with
      increased CRP have a markedly increased relative risk of AMI. Measurement of CRP
      may be useful in the cardiovascular risk assessment of patients with HIV.

PMID- 19387355
TI  - The impact of needle and syringe programs on HIV and HCV transmissions in
      injecting drug users in Australia: a model-based analysis.
AB  - OBJECTIVES: We aim to estimate how changes in sterile syringe distribution
      through needle-syringe programs (NSPs) may affect HIV and hepatitis C virus (HCV)
      incidence among injecting drug users (IDUs) in Australia. METHODS: We develop a
      novel mathematical model of HIV and HCV transmission among IDUs who share
      syringes. It is calibrated using biological and Australian epidemiological and
      behavioral data. Assuming NSP syringe distribution affects the number of times
      each syringe is used before disposal, we use the model to estimate the
      relationship between incidence and syringe distribution. RESULTS: HIV is
      effectively controlled through NSP distribution of sterile syringes {with the
      effective reproduction ratio below 1 [0.66 median, interquartile range (0.63
      0.70)] under current syringe distribution}. In contrast, HCV incidence is
      expected to remain high and its control is not feasible in the foreseeable
      future. The proportion of injections that are shared and the number of times each
      syringe is used before disposal are the driving factors of HCV incidence. The
      frequency in which each syringe is used can potentially be influenced by changes
      in syringe distribution. We estimate that if syringe distribution or coverage
      doubled, then annual incidence is likely to reduce by 50%. However, if it was
      decreased to one third of the current level, then approximately 3 times the
      incidence could be expected. CONCLUSIONS: This research highlights the large
      benefits of NSPs, puts forward a quantitative relationship between incidence and
      syringe distribution, and indicates that increased coverage could result in
      significant reductions in viral transmissions among IDUs.

PMID- 19387356
TI  - Recent HIV-1 infection detection: comparison of incidence estimates derived by
      laboratory assays and repeat testing data.
AB  - INTRODUCTION: Advances in laboratory methods capable of detecting recent HIV
      infection offer the promise of quickly and efficiently measuring HIV incidence in
      cross-sectional surveys, thereby greatly expanding the capabilities of
      surveillance programs. We compared HIV-1 incidence estimates derived from 3
      different methods: Vironostika-less sensitive, BED capture enzyme immuno assay
      (BED-CEIA), and repeat testing history. METHODS: A cross-sectional analysis was
      performed using HIV testing data from the population of all men who have sex with
      men presenting for serological HIV voluntary counseling and testing at the
      largest testing programs in San Francisco from 2000 to 2004 (n = 15,010).
      Specimens were evaluated for recent HIV-1 infection using Vironostika-LS and BED
      CEIA. Concordance between the 2 assays was assessed using the Kappa statistic.
      RESULTS: The BED-CEIA and Vironostika-LS concurred in 90% of specimen
      classifications (Kappa = 0.77; "good" strength of agreement). Predictors of
      recent HIV-1 infection common to both methods were unprotected receptive anal
      intercourse (P < 0.001), sex with a known HIV-positive partner (P < 0.001), and
      amphetamine use (P < 0.01). Temporal trends in HIV-1 incidence were also
      consistent and stable. CONCLUSIONS: There was good concordance in the
      classification of recent HIV-1 infection between BED-CEIA and Vironostika-LS and
      in the correlates of acquisition of infection. The findings suggest that these
      incidence assays can be used for the basic epidemiological purposes of measuring
      HIV-1 incidence, identifying populations at risk for infection, and tracking the
      leading edge of the epidemic over time.

PMID- 19387354
TI  - Prevalence and persistence of cervical human papillomavirus infection in HIV
      positive women initiating highly active antiretroviral therapy.
AB  - OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) DNA in
      cervical specimens from treatment-naive women initiating highly active
      antiretroviral therapy (HAART) and explore the longitudinal association of HPV
      DNA with CD4 count and HIV viral load (VL). METHODS: Women enrolled before HAART
      were evaluated at baseline, weeks 24, 48, and 96 with CD4 count, VL, and cervical
      swab for HPV DNA. RESULTS: The 146 subjects had a median CD4 count of 238 cells
      per microliter and VL of 13,894 copies per milliliter. Ninety-seven subjects
      (66%) had HPV DNA detected in the baseline specimen including 90 subjects (62%)
      positive for 1 or more high-risk HPV types. HPV DNA detection declined to 49% at
      week 96 and that of a high risk HPV type to 39%. The duration of follow-up was
      associated with decreased detection of HPV DNA of any type (P = 0.045) and of
      high-risk HPV types (P = 0.003). There was at most a marginal association between
      HAART response and loss of detection of cervical HPV DNA. CONCLUSIONS: Women
      initiating HAART had a high prevalence of cervical HPV DNA that declined over 96
      weeks of HAART. The relationship of CD4 count and VL response to the decline of
      cervical HPV DNA was not strong.

PMID- 19387357
TI  - Specific sex drug combinations contribute to the majority of recent HIV
      seroconversions among MSM in the MACS.
AB  - BACKGROUND: New HIV infections are being observed among men who have sex with men
      (MSM). Understanding the fusion of risky sexual behaviors, stimulant and erectile
      dysfunction drug use with HIV seroconversion may provide direction for focused
      intervention. METHODS: During the follow-up period (1998-2008), we identified 57
      HIV seroconverters among 1667 initially HIV-seronegative men. Time to
      seroconversion was modeled using Cox proportional hazards regression analysis for
      7 combinations of sex drugs (inhaled nitrites or "poppers", stimulants, and
      erectile dysfunction drugs) used at the current or previous semiannual visit,
      adjusting for other risk factors including sexual behavior, alcohol and other
      drugs used, and depression. Model-based adjusted attributable risks were then
      calculated. RESULTS: The risk of seroconversion increased linearly with the
      number of unprotected receptive anal sex partners (URASP), with hazard ratios
      ranging from 1.73 [95% confidence interval (CI): 0.75 to 4.01] for 1 partner, to
      4.23 (95% CI: 1.76 to 10.17) for 2-4 partners, and to 14.21 (95% CI: 6.27 to
      32.20) for 5+ partners, independent of other risk factors. After adjustment,
      risks for seroconversion increased from 2.99 (95% CI: 1.02 to 8.76) for men who
      reported using stimulants only (1 drug) to 8.45 (95% CI: 2.67 to 26.71) for men
      who reported using all 3 sex drugs. The use of any of the 7 possible sex drug
      combinations accounted for 63% of the 9-year HIV seroincidence in the Multicenter
      AIDS Cohort Study. When contributions of increased URASP and combination drug use
      were analyzed together, the total attributable risk for HIV seroconversion was
      74%, with 41% attributable to URASP alone and a residual of 33% due to other
      direct or indirect effects of sex drug use. CONCLUSIONS: Use of poppers,
      stimulants, and erectile dysfunction drugs increased risk for HIV seroconversion
      significantly in this cohort. These data reinforce the importance of implementing
      interventions that target drug reduction as part of comprehensive and efficacious
      HIV prevention strategies.

PMID- 19387358
TI  - Esthetic positioning of rigid internal fixation in tripod zygomatic fractures: an
      innovative surgical technique.
AB  - Tripod displaced zygomatic fractures are generally treated with rigid internal
      fixation at the intraorbital rim (IOR), frontozygomatic (FZ) suture, and
      zygomaticomaxillary buttress. Intraorbital rim fixation is associated with
      complaints of poor esthetic results and miniplate intolerance. Although different
      solutions were previously reported as 2-point fixation or resorbable fixation at
      the IOR, a 3-point fixation is considered the best choice for maintaining an
      optimal zygomatic stability after reduction. Consequently, the best goal is to
      perform a surgical technique that provides a 3-point fixation and avoids the
      consequence of subjective and objective alterations at the IOR and FZ areas. We
      propose an innovative technique that proved to be a simple, effective method to
      eliminate postsurgical sequelae due to rigid internal fixation positioning in the
      IOR and FZ areas.

PMID- 19387359
TI  - Oriental surgical protocol in orbital hypertelorism.
AB  - OBJECTIVE: To summarize and analyze the diagnosis, treatment protocol, and
      therapeutic effect of orbital hypertelorism in the past 30 years in our center.
      METHODS: This retrospective study reviews the records of 128 patients from 1978
      to 2008. Both radiologic measurements, such as the interorbital distance and the
      outer orbital distance, and anthropometric measurements, such as the width of the
      inner canthi (W-IC), the width of the palpebral fissure, the width of the face,
      and the nasofrontal angle, were conducted before and after the operation to
      evaluate both osseous and soft tissue alteration. An analysis of the etiology,
      surgical method, and complication has been undertaken. RESULTS: The main cause of
      orbital hypertelorism in our center was craniofacial cleft. Significant
      improvement in cranio-orbital appearance was noted, and 91.4% of the patients
      were satisfied with the surgical correction. Follow-up examinations showed a
      statistically significant difference between preoperative and postoperative
      measurements: interorbital distance; outer orbital distance; facial ratios W
      IC/width of the palpebral fissure and W-IC/width of the face (P < 0.01); and
      nasofrontal angle (P < 0.05). Temporary complications and side effects remained
      low, with cerebrospinal fluid leakage occurred as the major complication (6.3%).
      CONCLUSION: There are several important protocols regarding the management of
      orbital hypertelorism that will provide patients with great benefit in achieving
      more aesthetic facial appearance.

PMID- 19387360
TI  - Lateral deltopectoral flap: a new and extended flap.
AB  - Tissues of the pectoral area such as skin and pectoralis major muscle are used in
      safe and extended flaps for cervical and neck reconstructions. As blood supply is
      derived from medial vessels (internal mammary artery) or lateral (thoracodorsal
      and lateral thoracic arteries), 2 different flaps can be constructed: medial and
      lateral deltopectoral flaps. Medial deltopectoral flap was developed by Bakamjian
      as an axial-pattern skin flap, and its blood supply depends on perforating
      branches from the internal mammary artery. When either parasternal skin or
      pectoralis major muscle must be resected, this flap obviously cannot be used. In
      this article, a new lateral deltopectoral flap based on lateral pedicles (from
      axilla and lateral thoracic area) is described. The successful use of this
      lateral deltopectoral flap in an extended cervical and thoracic reconstruction
      after resection of a giant basal cell carcinoma demonstrates that it must be
      considered as an alternative technique.

PMID- 19387361
TI  - Bilateral orbital roof fracture.
AB  - Bilateral orbital roof fractures are rare events usually associated with high
      energy impact trauma. The clinical picture is often multiple because of
      involvement of cranial, cerebral, and facial injuries. The primary diagnostic and
      therapeutic approaches aim to safeguard the cerebral state and to intercept the
      consequences of severe orbital trauma. The latter may present dramatic events and
      determine permanent ocular bulb or optic nerve damage, even vision impairment and
      blindness. Immediate intraorbital decompression decreases the pressure exerting
      directly or indirectly on the optic nerve. Surgical decompression of the orbit
      was performed in a young man showing almost complete blindness after bilateral
      orbital roof fracture. The final result showed good recovery of vision and
      functional motility of the bulbs.

PMID- 19387362
TI  - Le premier siecle: one hundred years of progress in the treatment of Apert
      syndrome.
AB  - The year 2006 marked the 100th anniversary of the publication of Eugene Apert's
      article, De l'acrocephalosyndactylie in the Bulletin de la Societe des medecins
      des hospitaux de Paris. During the last century, much progress has been made in
      the understanding and treatment of this condition. A translation of Apert's
      original article is provided as is an overview of what has been learned during
      the last 100 years and what the future treatment of this condition may be.

PMID- 19387363
TI  - Interval hypoxic training improves autonomic cardiovascular and respiratory
      control in patients with mild chronic obstructive pulmonary disease.
AB  - OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is associated with
      cardiac autonomic nervous system dysregulation. This study evaluates the effects
      of interval hypoxic training on cardiovascular and respiratory control in
      patients with mild COPD. METHODS: In 18 eucapnic normoxic mild COPD patients (age
      51.7 +/- 2.4 years, mean +/- SEM), randomly assigned to either training or
      placebo group, and 14 age-matched healthy controls (47.7 +/- 2.8 years), we
      monitored end-tidal carbon dioxide, airway flow, arterial oxygen saturation,
      electrocardiogram, and continuous noninvasive blood pressure at rest, during
      progressive hypercapnic hyperoxia and isocapnic hypoxia to compare baroreflex
      sensitivity to hypoxia and hypercapnia before and after 3 weeks of hypoxic
      training. In double-blind fashion, both groups received 15 sessions of passive
      intermittent hypoxia (training group) or normoxia (placebo group). For the
      hypoxia group, each session consisted of three to five hypoxic (15-12% oxygen)
      periods (3-5 min) with 3-min normoxic intervals. The placebo group inhaled
      normoxic air. RESULTS: Before training, COPD patients showed depressed baroreflex
      sensitivity, as compared with healthy individuals, without evident chemoreflex
      abnormalities. After training, in contrast to placebo group, the training group
      showed increased (P < 0.05) baroreflex sensitivity up to normal levels and
      selectively increased hypercapnic ventilatory response (P < 0.05), without
      changes in hypoxic ventilatory response. CONCLUSION: Eucapnic normoxic mild COPD
      patients already showed signs of cardiovascular autonomic abnormalities at
      baseline, which normalized with hypoxic training. If confirmed in more severe
      patients, interval hypoxic training may be a therapeutic strategy to rebalance
      early autonomic dysfunction in COPD patients.

PMID- 19387364
TI  - Which markers of subclinical organ damage to measure in individuals with high
      normal blood pressure?
AB  - OBJECTIVE: Medical treatment of healthy individuals with high normal blood
      pressure (BP) is recommended if there is subclinical organ damage (SOD). We
      examined which markers of SOD to use based on their supplementary prognostic
      value. METHODS: In a population sample of 1968 individuals, aged 41, 51, 61 and
      71 years, without diabetes, prior stroke or myocardial infarction, not receiving
      any cardiovascular, antidiabetic or lipid-lowering medications, we measured urine
      albumin/creatinine ratio, carotid atherosclerotic plaques, carotid/femoral pulse
      wave velocity and left ventricular mass index. RESULTS: During a median follow-up
      of 12.8 years, the composite endpoint (CEP) of cardiovascular death, nonfatal
      myocardial infarction and stroke occurred in 153 individuals, of whom 32 had high
      normal BP. Presence of high normal BP was associated with increased risk of CEP
      [hazard ratio, 1.8 (95% confidence interval, 1.0-3.1; P = 0.046), optimal BP as
      reference group, adjusted for age and sex]. In the 337 individuals with high
      normal BP, using all four markers of SOD increased the sensitivity (number of
      CEPs in the group in which antihypertensive treatment was indicated divided by
      total number of CEPs) of the European Society of Hypertension risk classification
      chart significantly from 47 to 88% (P = 0.001) and the proportion of individuals
      in whom antihypertensive drug treatment was indicated from 22 to 57% (P < 0.001).
      Using two of pulse wave velocities of more than 12 m/s, atherosclerotic plaques
      or urine albumin/creatinine ratio of at least the 90th percentile did not produce
      significantly worse results. Seventy-five percent of individuals with three or
      more traditional risk factors had SOD. CONCLUSION: In healthy individuals with
      high normal BP, measuring two of pulse wave velocities, atherosclerotic plaques
      or urine albumin/creatinine ratio was sufficient to significantly improve risk
      prediction.

PMID- 19387365
TI  - Does fermented milk possess antihypertensive effect in humans?
AB  - The putative antihypertensive effect of milk after fermentation by lactic
      bacteria has attracted attention over the past 20 years. Research on fermented
      milk and hypertension has mainly focused on the content of peptides with in-vitro
      angiotensin converting enzyme-inhibitor effect. However, fermented milk products
      contain several proteins, peptides and minerals, all with possible different
      antihypertensive modes of actions. The burden of cardiovascular events in
      industrialized countries caused by hypertension is considerable. Diet
      modifications are one way to lower blood pressure, and fermented milk could be a
      feasible way. In this review, interventional human studies of the possible
      antihypertensive effect of fermented milk are evaluated. The results are
      diverging, and the antihypertensive effect is still debatable. Additionally,
      present knowledge of bioavailability and in-vivo actions of the peptides in
      fermented milk are discussed.

PMID- 19387366
TI  - Incorrect variables reported.

PMID- 19387367
TI  - Effect of resistive exercise on muscle damage in water and on land.
AB  - The purpose of this study was to compare the effects of resistance exercise in
      water and on land on blood levels of creatine kinase (CK), a known indirect
      marker of muscle damage. Nine men (age: 23 +/- 1.58 years; weight: 79.37 +/-
      11.15 kg; height: 176.33 +/- 4.09 cm), who had not practiced resistance training
      for at least 6 months before this experiment, performed 3 sets of maximum elbow
      flexion and extension exercises in water and on land, separated by 2-minute
      periods of rest. A 10-repetition maximum test was used to load control on land
      with free weights, and in water the exercise was performed at maximum velocity
      with aquatic resistance equipment. The duration of the exercise in water was the
      same as that performed on land, to reproduce the same metabolic route. Plasma CK
      activity was determined using a commercially available kit (Labtest Enzymatic-UV)
      before exercise, after exercise, and at 24 and 48 hours after exercise.
      Significant increases in CK were found at 48 hours postexercise on land
      (preexercise land: 160.75 +/- 96.05 UxL; 48 hours: 326.87 +/- 240.84 UxL), and
      significant differences were found between land and water (preexercise water:
      147.75 +/- 46.48 UxL; 48 hours: 121.75 +/- 30.86 UxL) for this measure. However,
      no significant differences were found in water. In conclusion, the water
      environment influenced the absence of significant muscle damage. This type of
      exercise protocol may be appropriate for situations in which limited muscle
      tissue damage is desired.

PMID- 19387368
TI  - Predicting one repetition maximum equations accuracy in paralympic rowers with
      motor disabilities.
AB  - Predicting one repetition maximum equations accuracy in paralympic rowers
      Resistance training intensity is prescribed using percentiles of the maximum
      strength, defined as the maximum tension generated for a muscle or muscular
      group. This value is found through the application of the one maximal repetition
      (1RM) test. One maximal repetition test demands time and still is not appropriate
      for some populations because of the risk it offers. In recent years, the
      prediction of maximal strength, through predicting equations, has been used to
      prevent the inconveniences of the 1RM test. The purpose of this study was to
      verify the accuracy of 12 1RM predicting equations for disabled rowers. Nine male
      paralympic rowers (7 one-leg amputated rowers and 2 cerebral paralyzed rowers;
      age, 30 +/- 7.9 years; height, 175.1 +/- 5.9 cm; weight, 69 +/- 13.6 kg)
      performed 1RM test for lying T-bar row and flat barbell bench press exercises to
      determine upper-body strength and leg press exercise to determine lower-body
      strength. One maximal repetition test was performed, and based on submaximal
      repetitions loads, several linear and exponential equations models were tested
      with regard of their accuracy. We did not find statistical differences for lying
      T-bar row and bench press exercises between measured and predicted 1RM values (p
      = 0.84 and 0.23 for lying T-bar row and flat barbell bench press, respectively);
      however, leg press exercise reached a high significant difference between
      measured and predicted values (p < 0.01). In conclusion, rowers with motor
      disabilities tolerate 1RM testing procedures, and predicting 1RM equations are
      accurate for bench press and lying T-bar row, but not for leg press, in this kind
      of athlete.

PMID- 19387369
TI  - Influence of exercise order on oxygen uptake during strength training in young
      women.
AB  - This study investigated the effect of resistance exercise order on the oxygen
      uptake (Vo2) and energy expenditure (EE). Ten trained women (age, 22 +/- 2 years;
      body mass index, 21 +/- 2 kgxm; peak Vo2, 42.2 +/- 2.9 ml kg min) volunteered for
      the study. Data were collected in 5 nonconsecutive days: (day 1) assessment of
      the peak Vo2 in a maximum effort ramp treadmill protocol; (days 2 and 3)
      determination of 10 repetition maximum (10RM) for the bench press (BP), machine
      shoulder press (SP), and pulley triceps extension (TE); and (days 4 and 5)
      performing 3 sets of each exercise with 3-minute rest intervals between sets and
      exercises until fatigue using 10RM in 2 sequences of opposite order (sequence A
      [SEQA]: BP, SP, TE; sequence B [SEQB]: TE, SP, and BP). Total Vo2 was assessed
      during all exercises, recovery intervals, and for 20 minutes after the end of the
      sequences. Energy expenditure was estimated from net Vo2 by subtracting rest
      values from total Vo2. No difference was found between the sequences for the
      total Vo2 (p = 0.68) and net energy cost (p = 0.29) (SEQA: 25.41 +/- 6.51 l and
      60.01 +/- 29.26 kcal; SEQB: 24.81 +/- 4.08 l and 57.02 +/- 15.25 kcal; mean +/-
      SD). Conversely, the Vo2 in the rest intervals between sets was higher for BP
      when it was placed at the end of SEQ B, and the same occurred with TE in SEQ A.
      In conclusion, the Vo2 was lower for a given exercise when it was performed first
      as compared with last in a training session for the upper limbs. However, these
      differences did not affect the overall Vo2 or EE during sequences performed in
      the opposite exercise order.

PMID- 19387370
TI  - Impact of fatigue on the position of the release arm and shoulder girdle over a
      longer shooting distance for an elite basketball player.
AB  - The purpose of this case study is to establish how a gradual increase in fatigue
      affects the position of the arms and shoulders during a long shot in a basketball
      game. For this purpose, Primoz Brezec, an elite National Basketball Association
      player, performed a total of 7 series of 20 shots from a distance of 7.24 m. The
      subject performed a special basketball motor task between individual series' of
      shots. The fatigue gradually increased with each motor task, and in the meantime,
      the subject's heart rate (HR) and blood lactate concentration (LA) were measured.
      The height of each jump during the shot at the basket was measured, and all shots
      were recorded using a system of 3 digital cameras operating at a frequency of 50
      Hz. Thereafter, a kinematic analysis was applied to calculate the height of the
      shoulder and wrist of the release arm, as well as the elbow and upper arm angles,
      with regard to the vertical line. The study results reveal statistically
      significant differences (p < 0.05) between the series of throws in all measured
      variables. The heights of the shoulder axis and of the wrist both decrease with
      growing fatigue. This is particularly apparent in the last series, i.e., in the
      conditions of maximum fatigue (HR = 96% HRpeak; LA = 9.7 mmolxL). Both measured
      angles decrease drastically in the last series of shots. The results of the study
      clearly demonstrate changes in the shooting technique as a consequence of
      moderate and, in particular, heavy fatigue. The findings also suggest the need
      for basketball coaches and basketball conditioning coaches to include moderate-
      and high-intensity exercise in their shooting practice sessions.

PMID- 19387371
TI  - Relationship of lat-pull repetitions and pull-ups to maximal lat-pull and pull-up
      strength in men and women.
AB  - To determine the relationships among selected shoulder pulling strength and
      endurance maneuvers, college men (n = 35) and women (n = 23) were evaluated for 1
      repetition maximum (1RM) lat-pull (LPmax), 1RM pull-up (PUmax), lat-pull
      repetitions-to-fatigue using 80% of 1RM (LPreps), and pull-up repetitions at 80%
      of 1RM (PUreps). PUmax was determined by adding to or counter-weighting the body
      mass to achieve one repetition. Men and women performed the 1RM with
      significantly more weight relative to body mass in the PUmax (1.16 +/- 0.15 and
      0.73 +/- 0.09, respectively) than in the LPmax (0.93 +/- 0.17 and 0.55 +/- 0.11,
      respectively). The correlation between LPmax and PUmax was higher in men (r =
      0.78; p < 0.01) than in women (r = 0.44; p > 0.05). Women performed significantly
      more PUreps (10.5 +/- 2.2) than men (8.1 +/- 1.9) but were equivalent to men in
      the LPreps (10.0 +/- 2.4 and 9.9 +/- 2.5, respectively). Men performed
      significantly more LPreps than PUreps, whereas the women were equivalent. Body
      composition components (lean body mass [LBM] and %fat) affected LPmax and PUmax
      to a greater degree in men than in women. Maximal strength performance in each
      lift in each sex could be predicted using the analogous muscular endurance
      exercise or body composition components.

PMID- 19387372
TI  - An evaluation of 30-km cycling time trial (TT30) pacing strategy through time-to
      exhaustion at average TT30 pace.
AB  - A paucity of research is available on the optimal pacing strategy for cycling
      events longer than 4 km. Anecdotal evidence suggests that an even pacing strategy
      is most suitable; however, controlled studies have only determined that a slow
      start is more suitable than a fast start pacing strategy. Currently, it is
      unclear which strategy is more effective for endurance cycling time trials. This
      study sought to identify differences in 30-km cycling time trial (TT30)
      performance related to pacing strategies by comparing individually chosen pacing
      strategy with time-to-exhaustion (TE) at the average power output achieved during
      TT30. Eight moderately trained male cyclists (Vo2max = 50.9 +/- 5.2 mlxkgxmin)
      performed 2 TT30 tests and 2 TE tests at the average power output of TT30 on a
      Velotron cycle ergometer at the same time of day, separated by at least 48 hours.
      During TT30, participants generally chose to use a 'fast start' pacing strategy,
      cycling at a speed relative to the TT average (TTAvg) of 103.1 +/- 2.2% during
      the first 5 km. There was no significant difference in performance time between
      the TE test and TT30. Starting pace (TT0-5) was significantly correlated with
      finishing pace (TT25-30) (r = -0.91; p < 0.01) and TE (r = 0.85; p < 0.01).
      Subjects cycling at a relative starting speed (RS0-5) >105% had a significantly
      longer TE than subjects cycling at <105%, whereas TT30 performance time was not
      different between the two groups. The present investigation provided indirect
      evidence that a fast start pacing strategy decreases finishing speed and overall
      performance in TT30, and increased TT performance can be achieved by selecting a
      starting pace no more than 5% above TTAvg.

PMID- 19387373
TI  - Strength tracking using the OMNI resistance exercise scale in older men and
      women.
AB  - Strength tracking uses ratings of perceived exertion (RPE) as a reference value
      to determine changes in strength as a function of a resistance training program.
      The purpose of this investigation was to determine if the OMNI Resistance
      Exercise Scale (OMNI-RES) could be used to track training-induced strength
      changes in older adults. Twenty-two men (64.3 + 3.2 years) and 27 women (63.8 +
      2.8 years) volunteered to participate. Subjects underwent a maximal lifting test,
      during which they estimated perceived exertion before and following 12 weeks of
      resistance exercise training. Leg press (LP), latissimus dorsi pull-down (LA),
      chest press (CP), leg extension (LE), leg curl (LC), arm extension (AE), and arm
      curl (AC) were performed. Paired samples t-tests were used to compare resistance
      lifted pre- and post-training at each criterion RPE (4, 6, and 8). One repetition
      maximum increased from pretraining to post-training (p < 0.05) for all exercises.
      The resistance lifted at each criterion RPE also increased (p < 0.05) during the
      12-week training session for every exercise. Older adults lifted more weight at 3
      criterion RPEs as their strength increased, providing an RPE-based procedure to
      track strength training changes using the OMNI-RES. As such, it seems that RPE
      from the OMNI-RES can be used to track strength in older adults.

PMID- 19387374
TI  - Day-to-day variation in heart rate at different levels of submaximal exertion:
      implications for monitoring training.
AB  - The HIMS test, which consists of controlled exercise at increasing workloads, has
      been developed to monitor changes in training status and accumulative fatigue in
      athletes. As the workload can influence the day-to-day variation in heart rate,
      the exercise intensity, which is associated with the highest sensitivity, needs
      to be established with the goal of refining the interpretability of these heart
      rate measurements. The aim of the study was to determine the within-subject day
      to-day variation of submaximal and recovery heart rate in subjects who reached
      different exercise intensities. Thirty-eight subjects participated in this study
      and after familiarization were allocated to 1 of 4 groups based on the percentage
      of predicted heart rate maximum that was elicited during the first test (i.e.,
      groups: <85, 85-90, 90-95, and >95% maximum heart rate). Variation in heart rate
      was determined for the following 4 days at a range of intensities (61-98% of
      maximum heart rate) and recovery periods. Variation in heart rate decreased with
      increasing exercise intensity in all groups. The lowest variation in heart rate
      was found at the end of the last stage of the test in the 85-90% group (3 +/- 1
      bxmin) and >95% group (3 +/- 2 bxmin). The lowest variation during the recovery
      periods occurred at the first minute after the last stage. Although there were no
      significant differences between the groups, the 85-90% group showed a tendency to
      have the lowest variation in heart rate. If changes in heart rate and heart rate
      recovery are to be monitored in athletes, a submaximal protocol should elicit
      heart rate between 85 and 90% of maximum heart rate, because this intensity is
      associated with the least day-to-day variation.

PMID- 19387375
TI  - Effects of different accentuated eccentric load levels in eccentric-concentric
      actions on acute neuromuscular, maximal force, and power responses.
AB  - This study examined the effects of different dynamic accentuated external
      resistance load levels during the eccentric(ECC) phase of ECC-concentric (CON)
      actions on acute neuromuscular, maximal force, and power responses in the bench
      press exercise in male subjects (age, = 32 +/- 4 years; n = 11). Four maximum
      strength sessions consisted of 1 repetition maximum (RM) lifts with traditional
      isoinertial resistances and of 1RM lifts with the different dynamic accentuated
      external resistance (DAER) loads of 100, 105, 110, and 120% of 1 RM for the ECC
      phase, whereas 100% of 1RM was constantly used for the CON phase. One explosive
      strength session consisted of explosive repetitions with the 50, 60, 70, 80, and
      90% of 1RM loads for the ECC phase, whereas 50% of 1RM was constantly used for
      the CON phase. Force, power, and electromyography (EMG) activation of agonist
      deltoid, pectoralis major, triceps brachii, and antagonist biceps brachii muscles
      were recorded. In all maximum strength DAER sessions (105/100%, 110/100%, and
      120/100%), CON 1RM and CON force reduced (p < 0.05) compared with the control
      condition (100/100%). ECC muscle activity did not differ in the DAER loading
      conditions compared with the control loading condition. In the explosive strength
      session, peak power increased significantly from the 50/50% condition compared to
      the condition of 77.3 +/- 3.2/50% (p < 0.001) that produced the highest power for
      each individual. ECC agonist EMG activity increased significantly from the 50%
      condition to that of the 77.3 +/- 3.2/50% condition (p < 0.05). The present data
      showed that the different loads used in the DAER bench press action did not
      enhance maximum concentric strength production, but concentric power output
      during explosive actions with the individualized optimal load was larger compared
      with the control condition.

PMID- 19387376
TI  - Muscle dysmorphia symptomatology and extreme drive for muscularity in a 23-year
      old woman: a case study.
AB  - We describe a 23-year-old woman with muscle dysmorphia symptomatology and extreme
      drive for muscularity. In addition to structured case study interviews, 3
      questionnaires and a series of semistructured interview questions were
      administered for elaboration on key issues. The case studies allowed for
      triangulation of data garnered from the questionnaires. Responses revealed high
      scores for drive for muscularity, moderate scores for the Adonis complex, and
      high scores for symptoms of muscle dysmorphia. Muscle dysmorphia and drive for
      muscularity are more prevalent in men; however, unique cases such as this need to
      be further explored both empirically and theoretically. Cross-cultural references
      are needed to assess the overall impact of global social influences. Instruments
      measuring muscle dysmorphia need to be devised and validated for women as well as
      men. The strength and conditioning professional needs to be both aware and
      vigilant in helping people affected with psychosomatic disorders such as muscle
      dysmorphia or exercise addiction.

PMID- 19387377
TI  - Comparison of two lower-body modes of endurance training on lower-body strength
      development while concurrently training.
AB  - The most recent American College of Sports Medicine (1998) recommendations for
      quantity and quality of exercise includes both resistance and endurance exercise
      components. Skeletal muscle adaptations to resistance-only and endurance-only
      programs may be different and possibly antagonistic when both types of training
      are imposed concurrently. The present study examined the effect of two different
      modes of lower-body endurance exercise (i.e., cycle ergometry and incline
      treadmill walking) on lower-body strength development with concurrent resistance
      training designed to improve lower-body strength (i.e., bilateral leg press 1
      repetition maximum [RM]). Thirty untrained participants (22 men and 8 women, ages
      18-23) were randomly assigned to one of 3 training groups (resistance only [R], N
      = 10; resistance + cycle ergometry [RC], N = 10; and resistance + incline
      treadmill [RT], N = 10). The 3 training groups exercised twice per week for 9
      weeks. The reduced frequency of exercise treatments were selected specifically to
      avoid overtraining for in-season athletes attempting to maintain offseason
      conditioning. Body mass and body composition measurements were taken pre- and
      post-training. Before training began, 3 weeks of training, 6 weeks of training,
      and after training, the participants also performed a 1RM test for lower-body
      strength. Analysis of variance comparisons with repeated measures revealed the
      following statistically significant changes (alpha = 0.05) in the 3 training
      groups over time: (a) when men and women were combined, body mass of R was
      significantly greater than RC and RT post-training; (b) body mass of men only was
      significantly greater than RC and RT post-training; (c) body composition of men
      only was significantly smaller for RC and RT compared with R; (d) when men and
      women were combined, percent change in strength revealed significantly greater
      gains in R compared with RT at 6 weeks; (e) when men and women were combined,
      percent change in strength revealed significantly greater gains in R compared
      with RC and RT post-training; (f) percent change in strength for men only was
      significantly greater for R compared with RT at 3 weeks; (g) percent change in
      strength for men only was significantly greater for R compared with RC and RT at
      6 weeks, and RC was significantly greater than RT at 6 weeks; (h) percent change
      in strength in men only was significantly greater for R compared with RC and RT
      post-training, and RC was significantly greater than RT post-training; and (i)
      percent change in strength in women was significantly greater in R compared with
      RT post-training. The findings confirm previous studies that reported attenuated
      strength development with concurrent resistance and endurance training compared
      with resistance-only training. More importantly, this study indicates that the
      mode of endurance exercise in concurrent training regimens may play a role in the
      development of strength. Specifically, it seems that cycling is superior to
      treadmill endurance training for an individual with the goal of developing
      strength in a multijoint movement (i.e., leg press or squat) in the lower-body
      because it more closely mimics the biomechanical movement of these exercises.

PMID- 19387378
TI  - Forward lunge: a training study of eccentric exercises of the lower limbs.
AB  - A few studies have shown that eccentric exercise is effective for prevention and
      treatment of muscle injuries. Most earlier studies on eccentric exercises have
      used training with advanced equipment. Forward lunges are considered eccentric
      exercises, and they may be performed without any equipment. These exercises are
      commonly used by sprint runners. We performed a prospective, randomized, 6-week
      training study comparing the effects of walking or jumping forward lunges on
      hamstring and quadriceps strength and function. Thirty-two soccer players were
      included in the study. The forward lunge training was done as an addition to
      ordinary soccer training twice a week for 6 weeks. The outcome was measured by
      the maximal hamstring and quadriceps strength tests and by functional tests with
      1-leg hop tests and 30-m sprint runs. Overall muscle pain was evaluated using a
      visual analogue scale score, and local pain was estimated with an algometer.
      Whereas the walking lunge improved hamstring strength, the jumping lunge resulted
      in sprint running improvements. Algometer testing showed a general increase in
      the pain detection thresholds of all subjects, including the controls. Thus,
      precautions should be taken when algometers are used for temporal studies of
      pain. Walking and jumping forward lunges can be used for improving hamstring
      strength and running speed in young soccer player. The findings may have
      relevance when designing protocols for prevention and rehabilitation of muscle
      injuries.

PMID- 19387379
TI  - Early-phase adaptations to a split-body, linear periodization resistance training
      program in college-aged and middle-aged men.
AB  - An 8-week, split-body, linear periodized resistance training program was
      completed by college-aged (CA: 18-22 years; n = 24) and middle-aged (MA: 35-50
      years; n = 25) men to determine early-phase adaptations in body composition and
      upper- and lower-body strength. Participants completed 2 upper-body and 2 lower
      body resistance training workouts each week. During weeks 1-4, subjects completed
      3-6 sets at a 10-repetition maximum (RM) intensity and increased to 8RM for weeks
      5-8. The 1RM strength levels were determined on the bench press and leg press,
      and 30-second Wingate tests were assessed at baseline and after 8 weeks of
      resistance training. Body composition was assessed using dual-energy X-ray
      absorptiometry (DXA). For selected data, delta values (post - pre values) were
      calculated and reported as mean +/- SEM. No changes (p > 0.05) were reported for
      peak and average Wingate power. Bench press (CA, 3.2 +/- 1.9 kg; MA, 6.2 +/- 3.3
      kg; p < 0.001) and leg press (CA, 25.0 +/- 4.4 kg; MA, 18.2 +/- 13.3 kg; p <
      0.001) 1RM significantly increased in both groups over time. Lean mass
      significantly increased over time in both groups (CA, 0.9 +/- 2.4 kg; MA, 1.1 +/-
      1.9 kg; p < 0.001). Significant group x time effects were seen for fat mass
      changes (CA, 0.5 +/- 1.3 kg; MA, -0.5 +/- 1.1 kg; p = 0.01) and % body fat
      changes (CA, 0.4 +/- 1.4%; MA, -0.7 +/- 1.1%; p = 0.01). These results indicate
      that performing a split-body, linearly periodized resistance training program for
      8 weeks significantly increases bench press 1RM, leg press 1RM, and DXA lean mass
      in CA and MA men. Furthermore, MA men lost significantly more fat mass and
      significantly decreased % body fat compared with CA men. A split-body, linearly
      periodized resistance training program may be used as an effective program to
      increase strength and lean mass in both young and MA populations.

PMID- 19387380
TI  - Hormonal and metabolic response in middle-aged women to moderate physical effort
      during aerobics.
AB  - The aim of this study is to estimate the metabolic and hormone response in middle
      aged women to acute physical aerobic exercise accompanied by music, the so-called
      "aerobics." The experiment (single 60-minute aerobics session) included 11 women
      aged between 30 and 50. The following variables were determined in blood samples
      collected from the participants four times (in fasting state [I], before exercise
      [II], after exercise [III], and after 12 hours of rest [IV]): concentration of
      lactic acid, glucose, free fatty acids, leptin, insulin, growth hormone,
      testosterone, and cortisol. Furthermore, the measurements included body mass
      before and after the exercise, and body temperature was taken in the auditory
      canal and on the forehead. The heart rate was registered during the exercise on a
      continuous basis. In all cases, the heart rate did not reach its maximum level,
      and on average, it amounted to approximately 70% of the maximum pulse rate.
      Therefore, this effort can be considered as submaximal. In all cases, we observed
      loss of body mass (from 0.2 to 0.7 kg) (p > 0.02) increase in the temperature
      measured on forehead. Significantly, accompanied by nonsignificant increase in
      the temperature measured on the tympanic membrane was registered. Single loading
      gives rise to change in hormone and metabolic profiles. Furthermore, a decrease
      in blood concentration of glucose before and after aerobics (p > 0.001) could be
      observed, and if the determination taken at measurement IV of glucose in blood is
      taken into consideration, then the value taken in measurement I is significantly
      the highest in relation to other measurements. Concentration of free fatty acids
      were increased (p > 0.002) after exercise and remained on the same level until
      the following day. The levels of insulin were significantly decreased, but growth
      hormone levels were increased. The exercise had no impact on testosterone
      concentration, whereas average blood concentration of leptin in the successive
      measurements showed a decreasing trend, although these changes are not
      statistically significant.Our observations provide the possibly full view of the
      physiologic reaction to the applied program of complex physical exercise
      accompanied by music, supporting the exercise's rhythm. The research program
      presented requires further investigation, e.g., what is the recommended frequency
      of the exercises applied on a weekly basis, and when should the intensity of the
      same increase.

PMID- 19387381
TI  - Effects of different accentuated eccentric loads on acute neuromuscular, growth
      hormone, and blood lactate responses during a hypertrophic protocol.
AB  - This study monitored acute neuromuscular responses and growth hormone (GH) and
      blood lactate (La) concentrations in the eccentric-concentric (ECC-CON)
      hypertrophic protocol by using various dynamic accentuated external resistance
      (DAER) loads in the bench press exercise. Male subjects (age = 32 +/- 4 years; n
      = 11) performed 4 sets of 10 repetitions with 2 minutes of recovery between the
      sets. The loads were 70, 80, 90, and 100% of 1 repetition maximum (RM) for the
      ECC phase, whereas 70% RM was constantly used for the CON phase.
      Electromyographic activity (EMG), ECC, CON, and isometric (ISOM) forces, serum GH
      and blood La, were measured at pre- and postloading. Significant reductions
      occurred in ISOM and CON pre- to postforces in all loading conditions (p < 0.01 -
      0.001). Pre- to postchange in blood La in the 90/70% condition (9.5 +/- 2.3
      mmolxL) was greater (p < 0.05) than in the control 70/70% condition (7.7 +/- 1.1
      mmolxL). The highest individual pre- to postchange in blood La was larger after
      the 90/70% (p < 0.001) condition compared with the 70/70% condition. The post-GH
      concentration in the 90/70% loading was 8.7 +/- 1.9 microgxL and in the abstract.
      --> 3.5 +/- 1.5 microgxL in the control condition, but the difference did not
      reach statistical significance. ECC EMG of the agonists increased with the
      increase in load but significantly only in the deltoid anterior (p < 0.01). A
      significant relationship was observed between the "optimal" ECC load and 1RM per
      body mass (BM)-ratio (r = 0.85; p < 0.05). The findings suggest that the acute
      metabolic and GH responses in the 90/70% condition were more favourable compared
      with the 70/70% condition, and a significant correlation between the optimal ECC
      load and 1RM per BM-ratio was observed. The findings can be applied into practice
      in designing exercise protocols in training for muscle hypertrophy and suggest
      the importance of individualized load selection for DAER exercises.

PMID- 19387382
TI  - Comparison of physiological responses to an incremental running test on
      treadmill, natural grass, and synthetic turf in young soccer players.
AB  - This study aimed to compare the physiological responses to a running test often
      used to assess lactate thresholds in soccer players when performed with an
      identical protocol on treadmill (Tr), natural grass (Nat), and synthetic turf
      (Synt). Eighteen young soccer players (mean +/- SD: age, 17.4 +/- 0.8 years; body
      mass, 66.2 +/- 6.7 kg; height, 175.8 +/- 5.7 cm) performed on each surface a
      multistage running test, including 4-minutes stages separated by a 1-minute rest,
      with initial speed set at 8 kmxh and increased of 2 km.h after each stage. Blood
      lactate concentration (La) and heart rate (HR) were assessed. The test ended when
      La exceeded 4 mmolxL. At each of the stages completed in the three conditions by
      all the subjects (8, 10, 12, and 14 kmxh), La was higher in Synt vs. both Nat and
      Tr with differences of at least 0.6 mmolxL (p < 0.05), whereas HR was higher (p <
      0.05) in Synt vs. Nat with differences from 4.3 bxmin (at 10 kmxh) to 6.4 bxmin
      (at 8 kmxh). Running speed at the 4 mmolxL La threshold was lower (p < 0.05) in
      Synt (13.1 +/- 1.1 kmxh) than in Nat (13.9 +/- 1.2 kmxh) and Tr (14.4 +/- 1.3
      kmxh). The La/HR curve obtained in Synt was shifted upward compared with the Nat
      and Tr curves, indicating higher La values at given HRs. These results could be
      mostly explained by adaptations of running mechanical patterns to surface
      properties that affect the energy requirements of running. This study emphasized
      the importance of testing soccer players on the specific surface used for
      training activities when assessing lactate threshold indices to prescribe and
      monitor field training.

PMID- 19387383
TI  - Effects of gender on physiological responses to strenuous circuit resistance
      exercise and recovery.
AB  - Few studies have focused upon the physiological responses to circuit weight
      training (CWT) in men and women, and an investigation of possible gender
      differences could lead to optimal exercise prescriptions and improved adaptation
      outcomes. The purpose of the study was to determine the effects of gender on
      cardiovascular and metabolic responses to CWT and consequent recovery. Ten
      healthy men and 10 healthy women completed an initial session to collect
      descriptive data and determine a 12 repetition maximum (12RM) for 6 different
      upper- and lower-body resistance exercises. This was followed by 2 identical
      sessions of a CWT protocol on 2 separate days at least 48 hours apart. The first
      session was used to familiarize subjects with the equipment and the testing
      protocol. The second session was used to determine physiological responses. Each
      subject performed 10 repetitions of 6 exercises for 3 circuits at a 12RM load.
      Vo2 and respiratory exchange ratio (RER) were continuously monitored, whereas
      heart rate (HR) and blood pressure (BP) were taken at the end of each circuit.
      Across the exercise session, men revealed greater absolute and relative Vo2,
      relative lean body mass Vo2, systolic BP (SBP), RER, and recovery Vo2 when
      compared with the female subjects. There were no differences in HR, diastolic BP
      (DBP), or recovery RER. The present study provides a greater insight into gender
      differences in cardiovascular and metabolic responses to circuit weight training.
      These gender differences should be taken into consideration for development of
      CWT protocols for men and women.

PMID- 19387384
TI  - A metronome for controlling the mean velocity during the bench press exercise.
AB  - Lifting velocity may have a great impact on strength training-induced
      adaptations. The purpose of this study was to validate a method including a
      metronome and a measurement tape as inexpensive tools for the estimation of mean
      lifting velocity during the bench press exercise. Fifteen subjects participated
      in this study. After determining their one repetition maximum (1RM) load, we
      estimated the maximum metronome rhythm (R) that each subject could maintain in
      the concentric phase for loads of 40 and 60% of 1RM. To estimate R, the 3
      repetitions with highest concentric power, as measured by means of a linear
      encoder, were selected, and their average duration was calculated and converted
      to lifting rhythm in beats per minute (bpm) for each subject. The range of motion
      was measured using a regular tape and kept constant during all exercises.
      Subjects were instructed to begin with the barbell at arm lengths and lower it in
      correspondence with the metronome beep. They subsequently performed 5 repetitions
      at 3 different rhythms relative to R (50, 70, and 90% R) for each training load
      (40 and 60% of 1RM). A linear encoder was attached to the bar and used as a
      criterion to measure the vertical displacement over time. For each rhythm, the
      mean velocity was calculated with the metronome (time) and the reference distance
      and compared with that recorded by the linear encoder. The SEM for velocity
      between both testing methods ranged from 0.02 to 0.05 m.s (coefficient of
      variation, 4.0-6.4%; Pearson's correlation, 0.8-0.95). The present results showed
      that the use of a metronome and a measurement tape may be a valid method to
      estimate the mean velocity of execution during the bench press exercise. This
      simple method could help coaches and athletes achieve their strength training
      goals, which are partly determined by lifting velocity.

PMID- 19387385
TI  - Age, weight, and the front abdominal power test as predictors of isokinetic trunk
      strength and work in young men and women.
AB  - First we tested the reliability of two new field tests of core stability (plank
      to fatigue test [PFT] and front abdominal power test [FAPT]), as well as
      established measures of core stability (isokinetic trunk extension and flexion
      strength [TES and TFS] and work [TEW and TFW]) over 3 days in 8 young men and
      women (24.0 +/- 3.1 years). The TES, TFS, TFW, and FAPT were highly reliable, TEW
      was moderately reliable, and PFT were unreliable for use during a single testing
      session. Next, we determined if age, weight, and the data from the reliable field
      test (FAPT) were predictive of TES, TEW, TFS, and TFW in 50 young men and women
      (19.0 +/- 1.2 years). The FAPT was the only significant predictor of TES and TEW
      in young women, explaining 16 and 15% of the variance in trunk performance,
      respectively. Weight was the only significant predictor of TFS and TFW in young
      women, explaining 28 and 14% of the variance in trunk performance, respectively.
      In young men, weight was the only significant predictor of TES, TEW, TFS, and
      TFW, and explained 27, 35, 42, and 33%, respectively, of the variance in trunk
      performance. In conclusion, the ability of weight and the FAPT to predict TES,
      TEW, TFS, and TFW was more frequent in young men than women. Additionally,
      because the FAPT requires few pieces of equipment, is fast to administer, and
      predicts isokinetic TES and TEW in young women, it can be used to provide a field
      based estimate of isokinetic TES and TEW in women without history of back or
      lower-extremity injury.

PMID- 19387386
TI  - Effects of two and five days of creatine loading on muscular strength and
      anaerobic power in trained athletes.
AB  - The purpose of this study was to establish the effects of 2 and 5 days of
      creatine loading, coupled with resistance training, on muscular strength and
      anaerobic performance in trained athletes. Seventeen trained men were randomly
      assigned to a creatine or a placebo group. The creatine supplementation group
      consumed 20 g of creatine per day (4 doses of 5 g per day), whereas the placebo
      group was given a placebo similar in appearance and taste over the 5-day
      supplementation duration. Anaerobic power and strength performance measures, in
      addition to blood and urine analysis, were conducted in the morning before the
      supplementation began and on the third and sixth day to establish the effect of 2
      and 5 days of creatine loading, respectively. The study found that a 5-day
      creatine loading regime coupled with resistance training resulted in significant
      improvements in both average anaerobic power, as measured by the 30-second
      Wingate test and back squat strength compared with just training alone. However,
      2 days of supplementation was not sufficient to produce similar performance gains
      as that observed at the end of 5 days of loading in trained men, despite
      increases in creatine uptake in the body. The standard 5-day loading regime
      should hence be prescribed to individuals supplementing with creatine for
      enhanced strength and power.

PMID- 19387387
TI  - Ballistic abdominal exercises: muscle activation patterns during three activities
      along the stability/mobility continuum.
AB  - The purpose of this study was to document the muscle activity and spine motion
      during several tasks requiring rapid abdominal contraction. Eight healthy men
      from a university population were instrumented to obtain surface electromyography
      of selected trunk and hip muscles, together with video analysis to calculate
      joint moments and electromagnetic lumbar spine position sensor to track spine
      posture. Exercises included a punch, throw, and a ballistic torso-stiffening
      maneuver. This study found that no muscle turned on significantly before any
      other muscle during both the 1-in. punch and ballistic torso-stiffening maneuver.
      Conversely, there was a significant order or muscle onset during the baseball
      throw. Muscles reached peak activation significantly before any other muscle
      during the baseball throw and 1-in. punch, but there were no significant
      differences for the torso-stiffening maneuver. The exercises quantified in this
      study demonstrated how muscle contraction dynamics change to meet differing
      demands for stiffening, for force/moment production, and for rapid movements.
      Specifically, it seems that there is an order of contraction when movement is the
      goal but not when just spine stability is required. Thus, a different intensity
      of abdominal bracing is required to achieve the different objectives of sports
      tasks and exercises.

PMID- 19387388
TI  - Alterations in pain perception after resistance exercise performed in the morning
      and evening.
AB  - The purpose of the present study was to examine whether changes in experimentally
      induced pain perception after acute resistance exercise (RE) are influenced by
      the time of day that RE is performed. Twenty-one recreationally trained (>1 year
      of regular recreational RE participation) young men (mean age = 21 years)
      completed 2 acute RE sessions at different times of day. One RE session was
      performed between 6:00 and 8:00 in the morning, and the other was performed
      between 6:00 and 8:00 in the evening. The RE sessions consisted of completing 3
      sets of 10 repetitions for 4 different exercises at 75% of each individual's 1
      repetition maximum. Assessments of pain threshold and pain ratings were obtained
      during exposure to an experimentally induced pressure pain stimulus before and
      after (1 and 15 minutes) each bout of RE. The results revealed that, irrespective
      of the time of day RE was performed, pain threshold increased significantly (p <
      0.01) at 1 minute after exercise. Pain ratings were also found to be
      significantly (p < 0.01) lower at 1 minute after RE in both the morning and
      evening. It is concluded that acute RE results in alterations in the perception
      of experimentally induced pressure pain and that this hypoalgesic response is not
      influenced by the time of day that RE is performed.

PMID- 19387389
TI  - Determinants of time to fatigue during nonmotorized treadmill exercise.
AB  - Treadmill exercise is commonly used for aerobic and anaerobic conditioning.
      During nonmotorized treadmill exercise, the subject must provide the power
      necessary to drive the treadmill belt. The purpose of this study was to determine
      what factors affected the time to fatigue on a pair of nonmotorized treadmills.
      Twenty subjects (10 men/10 women) attempted to complete 5 minutes of locomotion
      during separate trials at 3.22, 4.83, 6.44, 8.05, 9.66, and 11.27 kmxh. Total
      exercise time (<or=5 minutes) was recorded. Exercise time was converted to the
      number of 15-second intervals completed. Peak oxygen uptake (Vo2) was measured
      using a graded exercise test on a standard treadmill, and anthropometric measures
      were collected from each subject before their entrance into the study. A Cox
      proportional hazards regression model was used to determine significant
      predictive factors in a multivariate analysis. Treadmill speed and absolute peak
      Vo2 were found to be significant predictors of exercise time, but there was no
      effect of anthropometric characteristics. Gender was found to be a predictor of
      treadmill time, but this was likely attributable to a higher peak Vo2 in men than
      in women. The results were not affected by the type of treadmill tested in this
      study. Coaches and therapists should consider the cardiovascular fitness of an
      athlete or client when prescribing target speed because these factors are related
      to the total exercise time that can be achieved on a nonmotorized treadmill.

PMID- 19387390
TI  - Reliability of performance measurements derived from ground reaction force data
      during countermovement jump and the influence of sampling frequency.
AB  - Force platforms are used extensively to measure force and power output during
      countermovement jump (CMJ). The purpose of this study was to examine measurement
      reliability and validity of commonly used performance measurements derived from
      ground reaction force (GRF)-time data during CMJ and the influence of sampling at
      different frequencies. Twenty-four men performed 2 trials of CMJ on a force
      platform, and GRF-time data were sampled at a rate of 500 Hz. Data obtained at
      500 Hz were considered as the reference, and then data were resampled at 400,
      250, 200, 100, 50, and 25 Hz, using interpolation. Commonly used power, force,
      and velocity performance measures were obtained from GRF-time data. Reliability
      was assessed by intraclass correlation coefficient (ICC) and coefficient of
      variation (CV) between the 2 trials within the session. Peak power, peak force,
      and peak velocity were highly reliable across all sampling frequencies (ICC =
      0.92-0.98, CV = 1.3-4.1). Percentage differences from 500-Hz reference values
      ranged from -0.85 to 0.20% at 400 Hz, -1.88 to 0.89% at 250 Hz, -1.80 to 1.31% at
      200 Hz, -3.63 to 3.34% at 100 Hz, -11.37 to 6.51% at 50 Hz, and -13.17 to 9.03%
      at 25 Hz. In conclusion, peak power, force, and velocity measurements derived
      from GRF to assess leg extensor capabilities are reliable within a test session
      except for peak rate of force development and time to peak power. With regard to
      sampling frequency, scientists and practitioners may consider sampling as low as
      200 Hz, depending on the purpose of measurement, because the percentage
      difference is not markedly enlarged until the frequency is 100 Hz or lower.

PMID- 19387391
TI  - Analysis of seated and standing triple Wingate tests.
AB  - Observations of athletes in seated and standing cycling positions in laboratory
      and field settings have led to the perception that they produce different
      outputs. The purpose of this study was to determine whether there are differences
      in power output and physiological responses between seated and standing positions
      of athletes during 3 consecutive Wingate tests. Seven (n = 7) elite-level
      speedskaters completed 3 x 30-second Wingate tests (resistance = 7.5% body
      weight) with 3.5 minutes of recovery between each test in both seated and
      standing positions. During the recovery period, athletes pedaled against no
      resistance in the seated position. Testing was randomized and separated by at
      least 48 hours. Power output, heart rate, blood lactate, and muscle oxygenation
      data were collected. Statistical analysis of comparable tests (i.e., seated
      Wingate test 1 [WinD1] compared with standing Wingate test 1 [WinU1];
      WinD2:WinU2; WinD3:WinU3) revealed no significant differences between the seated
      and standing variables. Position during a short-duration maximal-effort exercise
      test on a stationary bike did not produce statistically different results in
      power, maximal heart rate, blood lactate, or muscle oxygenation. As no
      differences were detected between positions, practitioners can allow subjects to
      choose their position. Also, if a subject rises out of the seat during a "seated"
      test, this change may not affect the subject's physiological variables. However,
      transitioning from one position to the other during the test is not advised due
      to the possible chance of injury. It should be acknowledged that there may be
      reasons for stipulating one position over another (e.g., injuries, leg length).

PMID- 19387392
TI  - Acute effects of passive static stretching during warm-up on driver clubhead
      speed, distance, accuracy, and consistent ball contact in young male competitive
      golfers.
AB  - This investigation was conducted to determine the effect of 2 different warm-up
      treatments on clubhead speed, distance, accuracy, and consistent ball contact in
      15 young male competitive golfers. Two supervised warm-up treatments, an active
      dynamic warm-up with golf clubs (AD) and a 20-minute total-body passive static
      stretching routine plus an identical AD warm-up (SS), were applied before each
      performance testing session using a counterbalanced design on nonconsecutive
      days. Immediately after each warm-up treatment, subjects were instructed to hit
      10 full-swing golf shots with their driver after their normal preshot routine,
      with 1 minute of rest between trials. Significant (p < 0.05) decreases in
      clubhead speed (-4.19%), distance (-5.62%), accuracy (-31.04%), and consistent
      ball contact (-16.34%) were observed. Theoretical explanations for this acute
      decrease in performance include a more compliant muscle tendon unit, decreased
      neuromuscular reflex sensitivity, and neural inhibition attributable to the SS
      treatment. The results of this inquiry strongly suggest that a total-body passive
      static stretching routine should be avoided before practice or competition in
      favor of a gradual, active dynamic with golf clubs.

PMID- 19387393
TI  - Positioning during resistance elbow flexor exercise affects electromyographic
      activity, heart rate, and perceived exertion.
AB  - The main objective of this study was to compare electromyography (EMG), heart
      rate (HR), and perceived exertion (PE) during different elbow flexion exercises
      in standing position (biceps curl [BC] and adapted BC [ABC]) and seated position
      (preacher BC [PBC]). Twenty healthy subjects performed the dynamic 1-repetition
      maximum (1RM) test. The following week (1 exercise per day), these exercises were
      performed at 25, 30, 35, and 40% 1RM at 1 minute for each one (20 repetitions).
      Biceps brachii and brachioradialis root mean square (RMS), HR, and PE were
      recorded in the 5th (R5), 10th (R10), 15th (R15), and 20th (R20) repetitions.
      Effects of exercise type (BC x ABC x PBC), load level (25% 1RM x 30% 1RM x 35%
      1RM x 40% 1RM), and exercise duration (R5 x R10 x R15 x R20) were analyzed. The
      RMS of the elbow flexors in the PBC R20 was significantly lower than BC and ABC
      at 40% 1RM, and, in the same way, for all load levels, HR and PE were
      significantly lower in PBC R20 at 40% 1RM compared with BC and ABC. For all
      exercises, RMS, HR, and PE at 25% 1RM were significantly lower than at 40% 1RM.
      The execution of the exercises caused significant increases in the RMS, HR, and
      PE mainly between R5 compared with R15 and R20. In conclusion, different
      positions demand different neuromuscular (EMG), cardiovascular (HR), and
      sensorial (PE) responses. A decreased effort sensation in PBC at the same
      relative load level can contribute to better execution when standing and seated
      exercises are compared.

PMID- 19387394
TI  - Indirect assessment of lactate minimum and maximal blood lactate steady-state
      intensity for physically active individuals.
AB  - An indirect assessment of the running velocity corresponding to lactate minimum
      (LMind) and its validity to estimate the maximal blood lactate steady state
      (MLSS) were analyzed in 22 physically active men (24.6 +/- 4.1 years, 72.6 +/-
      8.0 kg, 1.75 +/- 0.1 m, 11.9 +/- 3.7% body fat). The participants were allocated
      into 2 different groups (G1 and G2). The running velocities (m x min)
      corresponding to the 1600-m time trial (1600 mV) and lactate minimum (LM) were
      determined for G1 (n = 12), whereas the G2 participants (n = 10) had their MLSS
      identified in addition to the 1600 mV and LM tests. The LM test consisted of a
      150-m sprint to elevate blood lactate ([lac]) followed by 10 minutes of recovery
      and then 6 x 800-m at 78, 81, 84, 87, 90, and 93% of 1600 mV, with the velocity
      corresponding to the lowest [lac] (YSI 2700S) identified in the LM test. The
      relationship between 1600 mV and LM values for G1 yielded the following equation
      for indirect assessment of LM velocity: LMind (m x min) = (0.7507 x 1600 mV) +
      21.575. The validity of the LMind was tested in the G2 participants by comparing
      its results with those of the MLSS. The MLSS was identified among 3-4 constant
      intensity sessions by considering the highest running velocity for which a [lac]
      variation was not higher than 0.05 mM x min. No differences were observed for the
      LM (200.7 +/- 16.8 m x min), LMind (200.8 +/- 15.1 m x min), and MLSS (201.0 +/-
      15.6 m x min) for G2, and there was high correlation and agreement among
      parameters. The LMind was considered valid for estimating LM and MLSS values if
      applied to physically active individuals with characteristics similar to those of
      the present study; thus, it is a practical and economical alternative for
      trainers who cannot directly determine MLSS.

PMID- 19387395
TI  - Effects of beta-hydroxy-beta-methylbutyrate supplementation during resistance
      training on strength, body composition, and muscle damage in trained and
      untrained young men: a meta-analysis.
AB  - Beta-hydroxy-beta-methylbutyrate (HMB) is a popular supplement in the resistance
      training community, with its use supported by claims of increased strength,
      muscle growth, and improved recovery; however, research outcomes are variable.
      Therefore, we meta-analyzed the effectiveness of HMB on strength, body
      composition, and muscle damage. Nine qualifying studies yielded 14 comparisons
      subcategorized by training experience (trained, untrained) to provide 12-13
      estimates of strength (upper body, lower body, overall average), 13 estimates of
      fat and fat-free mass, and 7 estimates of the muscle-damage marker creatine
      kinase. The meta-analysis comprised 394 subjects (age 23 +/- 2 years, mean +/-
      between-study SD) with 5 +/- 2 weeks' intervention and 5 +/- 6 h.wk of training.
      The estimates were analyzed using a meta-analytic mixed model with study sample
      size as the weighting factor that included the main-effect covariates to control
      for between-study differences in HMB dose, intervention duration, training load,
      and dietary cointervention. To interpret magnitudes, meta-analyzed effects were
      standardized using the composite baseline between-subject SD and were qualified
      using modified Cohen effect size thresholds. There were small benefits to lower
      body (mean +/- 90% confidence limit: 9.9% +/- 5.9%) and average strength (6.6 +/-
      5.7%), but only negligible gains for upper-body strength (2.1 +/- 5.5%) were
      observed in untrained lifters. In trained lifters, all strength outcomes were
      trivial. Combined (all studies), the overall average strength increase was
      trivial (3.7 +/- 2.4%), although uncertainty allows for a small benefit. Effects
      on fat and fat-free mass were trivial, and results regarding creatine kinase were
      unclear. Supplementation with HMB during resistance training incurs small but
      clear overall and leg strength gains in previously untrained men, but effects in
      trained lifters are trivial. The HMB effect on body composition is
      inconsequential. An explanation for strength gains in previously untrained
      lifters requires further research.

PMID- 19387396
TI  - Effects of nine weeks of beta-hydroxy-beta- methylbutyrate supplementation on
      strength and body composition in resistance trained men.
AB  - The dietary supplement beta-hydroxy-beta-methylbutyrate (HMB) is claimed to
      increase strength, lean body mass, and decrease fat mass when used in conjunction
      with resistance training. Although there is some support for these claims, the
      evidence is not conclusive, and it is even less so for resistance trained
      individuals. Therefore, we aimed to further elucidate the effects of HMB
      supplementation in trained men. A randomized, double-blind, controlled study
      design was used to investigate the effects of supplementing 22 resistance trained
      men with 3 g.d of HMB or corn starch placebo for 9 weeks with resistance
      training. The effect of HMB on strength was determined using the 1-repetition
      maximum (1RM) method for the lower body (leg extension) and upper body (bench
      press, bicep preacher curl) at baseline and after the supplementation period.
      Body composition was assessed by skinfolds and bioelectrical impedance analysis
      (BIA). Overall, 9 weeks' HMB supplementation resulted in a clear-cut, trivial
      increase in combined averaged strength measures of 1.6% (90% confidence limits:
      +/-4.3%). When considered in isolation, however, leg extension 1RM increased by a
      substantial 9.1% (90% confidence limits: +/-7.5%), but the effect on upper-body
      strength was inconclusive (bench press: -1.9 +/- 9.3%; bicep curl: -1.7 +/-
      4.7%). Based on BIA estimates, HMB had a decreasing (although inconclusive)
      influence on fat mass of -9 +/- 14%, but it had a clear, trivial effect on fat
      free mass of 0.2 +/- 2.2%. The magnitude of change in body mass was trivial, but
      the probability of substantial reductions in skinfold thicknesses ranged from
      negligible to likely. In previously trained men, supplementation of HMB in
      conjunction with resistance training provides a substantial benefit to lower-body
      strength, but it has negligible effects on body composition.

PMID- 19387398
TI  - Acute effects of a thermogenic nutritional supplement on energy expenditure and
      cardiovascular function at rest, during low-intensity exercise, and recovery from
      exercise.
AB  - The purpose of present study was to examine the acute effects of a thermogenic
      nutritional supplement on energy expenditure (EE) and cardiovascular function at
      rest, during low-intensity exercise, and recovery from exercise. Twenty-eight
      healthy sedentary participants (mean +/- SD; age, 22.3 +/- 1.9 years; body mass
      index, 24.0 +/- 3.7) volunteered for this randomized, double-blinded, placebo
      controlled, crossover study. Each experimental trial was divided into 4 phases:
      (a) 30 minutes of initial resting, followed by the placebo or thermogenic
      nutritional supplementation, (b) 50 minutes of postsupplementation resting, (c)
      60 minutes of treadmill walking (3.2-4.8 km x h), and (d) 50 minutes of
      postexercise recovery. Gas exchange variables measured by indirect calorimetry
      and heart rate (HR) were recorded during all 4 phases, blood pressure was only
      measured at rest, and rating of perceived exertion (RPE) was only recorded during
      exercise. EE and oxygen consumption rate (Vo2) were greater for the supplement
      than the placebo at 50 minutes after supplementation. Also, during the
      postsupplementation period, diastolic blood pressure (DBP) was higher at all time
      periods, whereas the respiratory exchange ratio (RER) was higher at 20 and 30
      minutes for the supplement. During exercise, only Vo2 and minute ventilation (VE)
      were greater for the supplement than the placebo, with HR being less than the
      placebo at 20 minutes for the men. Postexercise EE, Vo2, systolic blood pressure
      (SBP), DBP, and HR (men only) at 10, 20, 30, and 50 minutes were greater for the
      supplement than the placebo. These findings indicated that the thermogenic
      nutritional supplement increased resting EE and exercise Vo2 with only minimal
      effects on blood pressure and HR and no meaningful effects on RER or RPE. These
      results suggested that the combination of thermogenic ingredients in this
      nutritional supplement may be useful to help maintain a negative caloric balance
      but may not influence substrate use or perceived exertion.

PMID- 19387397
TI  - Effects of creatine monohydrate and polyethylene glycosylated creatine
      supplementation on muscular strength, endurance, and power output.
AB  - The purpose of this study was to examine the effects of a moderate dose of
      creatine monohydrate (CM) and two smaller doses of polyethylene glycosylated
      (PEG) creatine on muscular strength, endurance, and power output. Fifty-eight
      healthy men (mean +/- SD: age, 21 +/- 2 years; height, 176 +/- 6 cm; body mass
      [BM], 75 +/- 14 kg) volunteered and were randomly assigned to 1 of 4 groups: (a)
      placebo (PL; 3.6 g of microcrystalline cellulose; n = 15), (b) CM (5 g of
      creatine; n = 13), (c) small-dose PEG creatine (1.25 g of creatine: PEG1.25; n =
      14), or (d) moderate-dose PEG creatine (2.50 g of creatine: PEG2.50; n = 16).
      Testing was conducted before (pre-) and after (post-) a 30-day supplementation
      period. Measurements included body mass, countermovement vertical jump (CVJ)
      height, power output during the Wingate test (peak power [PP] and mean power
      [MP]), 1 repetition maximum bench press (1RMBP), 1RM leg press (1RMLP) strength,
      and repetitions to failure at 80% of the 1RM for bench press (REPBP) and leg
      press (REPLP). BM and MP (W) increased (p <or= 0.05) from pre- to
      postsupplementation for the CM group only, whereas 1RMBP and 1RMLP increased (p
      <or= 0.05) for the CM, PEG1.25, and PEG2.50 groups. CVJ height (cm and cm.kg), MP
      (W.kg), PP (W and W.kg), REPBP, and REPLP increased (p <or= 0.05) for all groups.
      These findings indicated that the recommended safe dose of 5 g.d of CM increased
      BM and improved muscle strength (1RMBP and 1RMLP). Smaller doses of PEG creatine
      (1.25 and 2.50 g.d) improved muscle strength (1RMBP and 1RMLP) to the same extent
      as 5 g.d of CM, but did not alter BM, power output, or endurance. When compared
      to the PL group, neither CM nor PEG creatine supplementation improved peak power
      output (CVJ or PP), MP, or muscle endurance (REPBP or REPLP). Thus, PEG creatine
      may have ergogenic effects that are comparable to those of CM, but with a smaller
      dose of creatine.

PMID- 19387399
TI  - Metabolic conditioning among soccer players.
AB  - To reduce the risk of overuse injuries, yet obtain optimal fitness development
      among soccer players, research comparing different training strategies is
      required. This study compared conventional group conditioning (GRP) to
      individualized training (IT) during the preseason among female college soccer
      players. Both groups participated in soccer practices; however, players were
      randomly assigned to supplemental conditioning differentiated by the use of
      player-specific heart rate training in the IT group. Changes in maximal oxygen
      consumption, anaerobic threshold, and rate of recovery were analyzed before and
      after 12 weeks of conditioning. Data analysis identified significantly (p < 0.05)
      greater improvements in the IT group in all 3 variables, despite considerably
      less training volume. Based on these data, it is apparent that catering training
      to the fitness level of each individual player can have a positive impact on
      training adaptations.

PMID- 19387400
TI  - Ponderal somatogram analysis of girth measurements by position in division III
      college football players.
AB  - Ponderal somatograms assessed body composition in four groups of Division III
      collegiate football players: offensive line (OL), defensive line (DL), offensive
      backs (OB), and defensive backs (DB). Ponderal somatograms evaluate body size and
      shape by converting muscular (shoulders, chest, biceps, forearm, thigh, and calf)
      and nonmuscular (abdomen, hips, knee, ankle, and wrist) girths into ponderal
      equivalent (PE) values. Anthropometric measurements, including stature, body
      mass, girths, and percent body fat by densitometry were collected in 82 players
      (22 OL, 12 DL, 20 OB, and 28 DB) during preseason camp. PE values were calculated
      for each girth as PE, kilograms = (girth, cm / k) x stature, decimeters, where k
      = k constant from Behnke's reference man. PE values were compared to body mass to
      indicate overdevelopment (PE > body mass) and underdevelopment (PE < body mass).
      OL was significantly heavier than DL (+15.6 kg), OB (+25.2 kg), and DB (+22.4
      kg). OL percent fat was significantly greater than DL (+5.9%), OB (+9.0%), and DB
      (+9.3%). Similar differences occurred in girths and PE values by position.
      Muscular components were generally overdeveloped, with the greatest
      overdevelopment in the biceps (OL + 16.0 kg, DL + 19 kg, OB + 14.2 kg, and DB +
      16.2 kg). Nonmuscular abdomen, hips, and knee were generally overdeveloped, with
      the greatest overdevelopment in the OL abdomen (+19.3 kg). Nonmuscular ankle and
      wrist were underdeveloped. Ponderal somatograms provide a relatively quick and
      simple method to translate girth measurements into ponderal equivalent values
      that seem to be position-specific among offensive and defensive linemen and
      backs. Somatograms provide an appraisal of body composition that helps coaches
      and athletes monitor the effectiveness of strength and conditioning programs.

PMID- 19387401
TI  - Power variables and bilateral force differences during unloaded and loaded squat
      jumps in high performance alpine ski racers.
AB  - The purpose of this paper was to investigate the power-load relationship and to
      compare power variables and bilateral force imbalances between sexes with squat
      jumps. Twenty men and 17 women, all members of the Austrian alpine ski team
      (junior and European Cup), performed unloaded and loaded (barbell loads equal to
      25, 50, 75, and 100% body weight [BW]) squat jumps with free weights using a
      specially designed spotting system. Ground reaction force records from 2 force
      platforms were used to calculate relative average power (P), relative average
      power in the first 100 ms of the jump (P01), relative average power in the first
      200 ms of the jump (P02), jump height, percentage of best jump height (%Jump),
      and maximal force difference between dominant and nondominant leg (Fmaxdiff). The
      men displayed significantly higher values at all loads for P and jump height (p <
      0.05). No significant differences were found in P01. The men had significantly
      higher P02 at all loads except 75% BW). Maximum P was reached at light loads (men
      at 25% BW and women at 0% BW), and P decreased uniformly thereafter. Individual
      power-load curves show a deflection point. It is proposed that the load where the
      power-load deflection point occurs be used as the power training load and not the
      load at which maximum P is reached. It is also proposed that loads not be
      described in %1-repetition maximum (RM), but as %BW. This system can be used to
      safely assess and train power with loaded jumps and free weights.

PMID- 19387402
TI  - The evaluation of the running speed and agility performance in professional and
      amateur soccer players.
AB  - The professional and amateur soccer players were tested to determine the running
      speed and agility performance by playing positions. The sample included 108
      professional male soccer players at the national level and 79 amateur male soccer
      players at a regional level on teams from 10 clubs in Turkey. The study involved
      the players being assessed by the 10- x 5-m shuttle run test ( 10 x 5 SRT) on a
      soccer field in a soccer season.The difference between the mean scores of the
      professional and amateur players is significant. Differences between mean scores
      according to playing positions of soccer players are not significant.In
      conclusion, professional soccer players' running speed and agility performances
      are higher than amateur soccer players. In addition, these results indicate that
      all soccer players have the same running speed and agility performance in
      accordance with their different playing positions. Coaches should consider
      individual training programs based on the positional role of soccer players.

PMID- 19387403
TI  - Blood metabolites during basketball competitions.
AB  - This study examined basketball game blood hormonal and metabolite responses in 38
      (8 guards, 18 forwards, and 12 centers) male national elite-junior players (age,
      18.2 +/- 0.5 years; height, 1.89 +/- 0.1 m; body mass, 80.3 +/- 6.7 kg; body fat,
      8.2 +/- 5.6%; maximum oxygen uptake Vo2max], 52.8 +/- 2.4 mlxkgxmin). At the
      moment of the investigation, players had 8 +/- 1.6 years of competitive
      experience. Blood samples were collected at the beginning, at halftime, and at
      fulltime of 6 junior competitive games (Tunisian under 19 basketball
      championship). Game intensity was assessed monitoring heart rates (HR). During
      the game, players attained 93 +/- 2% of maximal HR. Triglycerides (TG) and free
      fatty acids (FFA) concentrations significantly increased during the game, most
      markedly so in the second half. Postgame TG and FFA concentrations were
      significantly (p < 0.05 and p < 0.001, respectively) lower for guards (1.48 +/-
      0.22 and 0.88 +/- 0.14 mmolxL, respectively) than for centers (1.88 +/- 0.30 and
      1.08 +/- 0.09 mmolxL, respectively). Plasma glucose significantly increased at
      halftime (from 4.05 +/- 1.27 to 5.98 +/- 0.88 mmolxL; p < 0.001) but decreased in
      the second half. Serum insulin (INS) progressively decreased for all players
      during the game, whereas serum cortisol increased at the end of the first half
      (from 333 +/- 129 to 487 +/- 209 nmolxL; p < 0.001) to remain increased
      throughout the second half.Basketball game demands seem to induce significant
      metabolic-hormonal changes on players. Higher values of HR and glycemia were
      observed in the first half, but a more important increase of lipolytic variables
      was recorded in the second half. Changes in metabolic markers are role-dependent.

PMID- 19387404
TI  - The effects of a 7-week heavy elastic band and weight chain program on upper-body
      strength and upper-body power in a sample of division 1-AA football players.
AB  - The purpose of this study was to explore the effects of a 7-week heavy elastic
      band and weighted-chain program on maximum muscular strength and maximum power in
      the bench press exercise. Thirty-six (n = 36) healthy men aged 18-30 years old,
      from the Robert Morris University football team, volunteered to participate in
      this study. During the first week, predicted 1 repetition maximum (1RM) bench
      press and a 5RM speed bench press tests were conducted. Subjects were randomly
      divided into 3 groups (n = 12): elastic band (EB), weighted chain (WC), and
      traditional bench (C). During weeks 2-8 of the study, subjects were required to
      follow the prescribed resistance training program. Mean and SD of the predicted
      1RM bench press and 5RM speed bench press were computed. A two-factor (method X
      time) analysis was applied to identify significant differences between the
      training groups. Significance was set at alpha = 0.05. Results indicated a
      significant time (p < 0.05) but no group effect for both predicted 1RM (kg) and
      5RM peak power tests (watts). Although not significant, results did show greater
      nonsignificant improvements in the EB (848-883 W) and WC groups (856-878 W) vs.
      control (918-928 W) when the 2 highest and greatest values were selected
      regarding peak power. The use of EB and WC in conjunction with a general off
      season strength and conditioning program can increase overall maximum upper-body
      strength in a sample of Division 1-AA football players. These types of training
      modalities add a unique training style and more flexibility with respect to
      exercise prescription for athletes and strength practitioners.

PMID- 19387405
TI  - Maximal anaerobic power test in athletes of different sport disciplines.
AB  - The aim of this study was to investigate the values of anaerobic energetic
      capacity variables in athletes engaged in different sport disciplines and to
      compare them in relation to specific demands of each sport. Wingate anaerobic
      tests were conducted on 145 elite athletes (14 boxers, 17 wrestlers, 27 hockey
      players, 23 volleyball players, 20 handball players, 25 basketball players, and
      19 soccer players). Three variables were measured as markers of anaerobic
      capacity: peak power, mean power, and explosive power. The highest values of peak
      power were measured in volleyball 11.71 +/- 1.56 W.kg and basketball players
      10.69 +/- 1.67 W.kg, and the difference was significant compared with the other
      athletes (p <or= 0.05). The lowest value of peak power (8.58 +/- 1.56 W.kg) was
      registered in handball players. The mean power variable showed a similar
      distribution as peak power among groups. The highest values of explosive power
      were also registered in volleyball 1.75 +/- 0.33 W.s.kg and basketball players
      1.64 +/- 0.35 W.s.kg, but there was no significant difference in values between
      volleyball players and wrestlers, between boxers and wrestlers, between boxers
      and basketball players, and between volleyball and hockey players (p > 0.05). The
      measured results show the influence of anaerobic capacity in different sports and
      the referral values of these variables for the elite male athletes. Explosive
      power presented a new dimension of anaerobic power, i.e., how fast maximal energy
      for power development can be obtained, and its values are high in all sports
      activities that demand explosiveness and fast maximal energy production. Coaches
      or other experts in the field could, in the future, find useful to follow and
      improve, through training process, one of the variables that is most informative
      for that sport.

PMID- 19387406
TI  - Physiological correlates of golf performance.
AB  - Golf is now a sport where physical training is an integral component of elite
      players' practice and contributes to the ability to play at a high level
      consistently and without injury. Relationships between physical conditioning and
      golf performance have not been reported. Therefore, the objective of this
      research was to identify physiological correlates of golf performance in elite
      golfers under laboratory (ball speed and distance) and tournament conditions
      (average score, greens in regulation, short game measures, and putting
      accuracy).The correlation analysis revealed significant associations between
      mass, height, body mass index, sit height, arm length, and predicted Vo2max and
      golf measures. Significant correlations were noted between anterior abdominal
      muscle endurance and driver carry distance (r = 0.38; P = 0.04) and average putt
      distance after a chip shot (r = -0.44; P = 0.03), between dominant side abdominal
      muscle endurance and average putt distance after a chip shot (r = -0.43; P =
      0.03), and between nondominant-side abdominal muscle endurance and average putt
      distance after a sand shot (r = -0.59; P = 0.001). Further correlations were
      found among sit and reach and driver carry distance (r = -0.36; P = 0.04), 5-iron
      ball speed (r = - 0.41; P = 0.02), 5-iron carry distance (r = -0.44; P = 0.01),
      and score (r = 0.43; P = 0.03). Correlation analysis revealed significant
      associations among peripheral muscle test results, golf driver results, 5-iron
      ball measures, score, and putting efficacy.These results may be important for
      developing training programs based on sound physiological rationale and for the
      development of talent identification programs. Results suggest that core strength
      and stability, flexibility, balance, and peripheral muscle strength are
      correlated with golf performance and should be included in golf training
      programs.

PMID- 19387407
TI  - The influence of hand paddles on the arm coordination in female front crawl
      swimmers.
AB  - The purpose of the research was to determine the influence of hand paddles on the
      arm coordination in female front crawl swimmers. Ten female swimmers swam at a
      maximal intensity 25 m without, with small hand paddles (116 cm), and with large
      hand paddles (286 cm). Four S-VHS cameras were used to record the underwater
      motion of both arms, and the digitizing of selected points onto the subject's
      body was undertaken using the Ariel Performance Analysis System. The mean
      swimming velocity, the stroke length, the stroke rate, the relative duration of
      the separate phases of the stroke, and the index of coordination were then
      calculated. The index of coordination was defined as the time interval between
      the propulsive phases of the 2 arms expressed as a percentage of the mean
      duration of the stroke cycle. The results showed that when the hand paddles were
      worn, the mean swimming velocity (p < 0.05) and the stroke length (p < 0.05) were
      significantly increased, whereas the stroke rate was significantly decreased (p <
      0.05). When large paddles were worn, the relative duration of the whole
      propulsive phase was significantly decreased (p < 0.05), and the relative
      duration of the nonpropulsive phase was significantly increased (p < 0.05).
      However, the index of coordination was remained unchanged under the 3 measurement
      conditions (p = 0.895). It was concluded that in front crawl hand-paddled
      swimming, significant increases of the swimming velocity was not caused by
      modifications in the pattern of arm coordination. Thus, hand-paddled swimming
      should not be used as a tool to alter the time sequence of the application of
      propulsive forces generated from the 2 arms.

PMID- 19387408
TI  - Could the deep squat jump predict weightlifting performance?
AB  - This research was carried out with the aim of describing the deep squat jump
      (DSJ) and comparing it with the squat (SJ) and countermovement (CMJ) jumps, to
      introduce it as a strength testing tool in the monitoring and control of training
      in strength and power sports. Forty-eight male subjects (21 weightlifters, 12
      triathletes, and 15 physical education students) performed 3 trials of DSJ, SJ,
      and CMJ with a 1-minute rest among them. For the weightlifters, snatch and clean
      and jerk results during the Spanish Championship 2004 and the 35th EU
      Championships 2007 were collected to study the relationship among vertical jumps
      and weightlifters' performance. A 1-way analysis of variance (ANOVA) showed
      significant differences between groups in the vertical jumps, with the highest
      jumps for the weightlifters and the lowest for the triathletes. An ANOVA for
      repeated measures (type of jump) showed better results for DSJ and CMJ than SJ in
      all groups. A linear regression analysis was performed to determine the
      association between weightlifting and vertical jump performances. Correlations
      among the weightlifting performance and the vertical jumps were also calculated
      and determined using Pearson r. Results have shown that both CMJ and DSJ are
      strongly correlated with weightlifting ability. Therefore, both measures can be
      useful for coaches as a strength testing tool in the monitoring and control of
      training in weightlifting.

PMID- 19387409
TI  - Effects of Partner's Improvisational Resistance Training on dancers' muscular
      strength.
AB  - The purpose of this study was to observe the effects of Partner's Improvisational
      Resistance Training (PIRT) on muscular strength, body circumference, and body fat
      percentage in 10 female college-age dancers in comparison with 8 female dancers
      in a control group. The PIRT program, based on the concepts of manual resistance
      training, is the application of contact improvisation in a systematic strength
      development program, which proposes a way of contextualizing muscular strength
      development within the dance class. The program lasted 8 weeks, meeting 3 times
      weekly for 60-minute sessions. The muscular strength pre- and posttests included
      1-repetition maximum (1RM) for leg extension, leg flexion, leg press, bench
      press, lat pulldown, back extension, and modified sit-up. Hydrostatic weighing
      for body composition and circumference measures on the waist, hip, shoulder,
      upper arm, and thigh were made pre- and posttest analyses. There were no
      significant pretest differences between the groups for age, height, body weight,
      body fat percentage, any of the circumference measures, or 5 of the 7 muscular
      strength measures. At posttest, neither group showed significant changes in total
      body weight, body fat percentage, or lean body weight. The experimental group
      showed significant decrements in the waist and hip circumference measures, and
      all other body circumference changes were nonsignificant. The experimental group
      showed significant changes from pretest to posttest for all seven 1RM strength
      measures and greater absolute and relative strength improvements in 5 measures
      compared with the control group. Thus, the 8-week PIRT program for female dancers
      was found effective in improving overall muscular strength and decreasing
      circumference in the waist-hip region, but it did not elicit significant changes
      in body composition.

PMID- 19387410
TI  - Efficacy of interval-based training on conditioning of amateur field hockey
      players.
AB  - This research aimed to critically examine the effectiveness of a time-limited and
      distance-regulated interval training program on subelite field hockey players.
      Subjects comprised 22 women (26.1 +/- 4.5 years, 62.8 +/- 7.4 kg, 1.7 +/- 0.9 m)
      and 22 men (22.1 +/- 3.2 years, 74.9 +/- 5.4 kg, 1.8 +/- 0.5 m) field hockey
      players. Performance tests included a standard 20-m multiple-stage shuttle run
      (MSSR), a 1000-m repeated-effort (x3) time trial (RTT), and a 100-m repeated
      effort (x3) shuttle run (RSR) in an ascending pyramid order. The training program
      was administered separately to the women and men after a traditional, single
      peak, 4-week mesocycle, with the fourth week for recovery. Training consisted of
      an average total sprint distance of 3000 m per session during a 20-week data
      collection period, with testing administered pre and post. Initial athlete
      profiling showed a significant (p < 0.05) gender difference on all performance
      tests. The MSSR results were 8.6 +/- 2.5 (range 6.7-10.7) and 12.1 +/- 2.4 (10.2
      13.5) women and men, respectively. The RTT and RSR times for women and men were
      5:34 +/- 0:30 seconds (4:31-6:21), 5:14 +/- 0:30 seconds (4:27-6:02), 4:12 +/-
      0:13 seconds (3:50-4:36), and 4:06 +/- 0:13 seconds (3:47-6:02), respectively.
      After 20 weeks of training, a small to moderate effect size (ES) was calculated
      for the women's (n = 12) MSSR (ES = 0.74) and RSR (ES = 0.50) results. A distinct
      improvement in the MSSR resulted after training for men (n = 16), with a moderate
      ES (1.34). In contrast, completion times in RSR were marginally reduced, with a
      small ES (0.49). The findings demonstrate that a 3000-m interval-based
      conditioning program, when conducted in conjunction with normal-skill game play
      training, can lead to significant improvements in player conditioning during a
      competitive season. Future research should employ modified performance tests that
      more accurately reflect the nature of the game.

PMID- 19387411
TI  - Amplitude variables of circle on the pedagogic pommel horse in gymnastics.
AB  - The movement amplitude is a key component of numerous elements in gymnastics. The
      purpose of the present study is to highlight the most pertinent amplitude
      variable of the circle performed on the pedagogic pommel horse. Twelve gymnasts
      (6 expert gymnasts vs. 6 nonexpert gymnasts) performed 10 circles on this event.
      A Vicon 512 system was used to record the 3-dimensional position of 11 markers
      fixed on the gymnasts. Our results revealed than 4 amplitude variables permitted
      us to significantly discriminate the levels of performance of the gymnasts (p <
      0.05): shoulder extension in front phase, body alignment, shoulder diameter, and
      ankle diameter. In a training perspective, this result could help coaches focus
      their advice and pedagogic situations on the pertinent technical criteria. Then,
      a stepwise discriminant analysis performed on the 4 previously selected variables
      showed that 2 variables allowed us to accurately discriminate the circle
      amplitude: ankle diameter and body alignment. These 2 variables can be used by
      coaches as a specific index to objectively determine the performance levels of
      gymnasts and to measure improvement in movements after specific training.

PMID- 19387412
TI  - The relationship of heart rate and lactate to cumulative muscle fatigue during
      recreational alpine skiing.
AB  - Common indices of fatigue may not respond similarly between downhill skiing and
      other activities because of the influence of factors such as snow conditions,
      changing terrain, and skiing style. The purpose of this study was to investigate
      the relationship and predictors of common fatigue indices during downhill skiing.
      Ten healthy female recreational skiers skied for 3 hours under standardized
      conditions. Feedback on heart rate (HR) and finishing time were given to each
      skier at the end of each run to maintain a relatively stable load. A chronic
      stress score (Cstress) was calculated from creatine kinase (CK), cortisol, and
      isometric endurance. Finishing times and HR from runs 2, 12, and 24 were similar.
      Heart rate averaged 82% of HRmax. Heart rate was an insignificant predictor (p =
      .65) and was poorly correlated (r = 0.16) to Cstress. Blood lactate (LA) was a
      significant predictor of the Cstress (p = 0.05; r = 0.62). Pre- to postskiing
      peak forces were not different (p = 0.62), but skiers experienced a significant
      decrease in isometric endurance from 106.1 +/- 29.6 to 93.2 +/- 24.0 seconds.
      Endurance decreased by 13%, whereas cortisol and CK increased by 16 and 42%,
      respectively. Isometric contraction endurance and blood LA were significant
      predictors of overall stress. Individual compensation mechanisms and skiing style
      contributed to highly variable responses during skiing. Whereas HR may indicate
      stress within a given run, it is not a significant indicator of Cstress and
      fatigue during recreational alpine skiing. However, the cumulative stress
      variables and LA can be used in field testing of skiers. It is suggested that LA
      is a practical on-hill marker of chronic stress.

PMID- 19387413
TI  - Injury reduction effectiveness of selecting running shoes based on plantar shape.
AB  - Popular running magazines and running shoe companies suggest that imprints of the
      bottom of the feet (plantar shape) can be used as an indication of the height of
      the medial longitudinal foot arch and that this can be used to select
      individually appropriate types of running shoes. This study examined whether or
      not this selection technique influenced injury risk during United States Army
      Basic Combat Training (BCT). After foot examinations, BCT recruits in an
      experimental group (E: n = 1,079 men and 451 women) selected motion control,
      stability, or cushioned shoes for plantar shapes judged to represent low, medium,
      or high foot arches, respectively. A control group (C: n = 1,068 men and 464
      women) received a stability shoe regardless of plantar shape. Injuries during BCT
      were determined from outpatient medical records. Other previously known injury
      risk factors (e.g., age, fitness, and smoking) were obtained from a questionnaire
      and existing databases. Multivariate Cox regression controlling for other injury
      risk factors showed little difference in injury risk between the E and C groups
      among men (risk ratio (E/C) = 1.01; 95% confidence interval = 0.88-1.16; p =
      0.87) or women (risk ratio (E/C) = 1.07; 95% confidence interval = 0.91-1.25; p =
      0.44). In practical application, this prospective study demonstrated that
      selecting shoes based on plantar shape had little influence on injury risk in
      BCT. Thus, if the goal is injury prevention, this selection technique is not
      necessary in BCT.

PMID- 19387414
TI  - Hormone use and lung cancer incidence: the Rancho Bernardo cohort study.
AB  - OBJECTIVE: This study examines the association of hormone use and lung cancer
      among women. METHODS: This is a prospective study of 2,861 women aged 31 to 79
      years from the Rancho Bernardo cohort. After enrollment in 1972 to 1974, women
      were followed up for 31 years for morbidity and mortality. Incident lung cancer
      was based on self-report or death certificates. Diagnosis was validated from the
      California Cancer Registry for cases that occurred after 1988. Cox proportional
      hazard models were used to estimate the adjusted association of hormone use and
      lung cancer. RESULTS: During the 31-year follow-up, 87 women developed lung
      cancer. There was no association between hormone use and lung cancer (hazard
      ratio, 1.13; 95% CI, 0.73-1.73). Stratification by age 55 years (proxy for
      menopause status) showed divergent results. In women 55 years and older, lung
      cancer risk was 1.58 (95% CI, 0.95-2.53), whereas in women younger than 55 years,
      lung cancer risk was 0.44 (95% CI, 0.16-1.23). The confidence intervals for both
      groups contained the null value. CONCLUSIONS: Although not statistically
      significant, our results from a long follow-up suggest that postmenopausal women
      on hormone therapy may have an increased risk of lung cancer, whereas younger
      women do not.

PMID- 19387415
TI  - Relationships among serum receptor of nuclear factor-kappaB ligand,
      osteoprotegerin, high-sensitivity C-reactive protein, and bone mineral density in
      postmenopausal women: osteoimmunity versus osteoinflammatory.
AB  - OBJECTIVE: The aim of this study was to investigate the correlations among
      circulating osteoprotegerin (OPG), the receptor activator of nuclear factor
      kappaB ligand (RANKL), high-sensitivity C-reactive protein (hsCRP), and bone
      mineral density (BMD) in healthy postmenopausal women. METHODS: In a population
      based study, highly specific enzyme-linked immunosorbent assay methods were used
      to evaluate the sera of 382 healthy Iranian postmenopausal women (mean age +/-
      SD, 58.7 +/- 7.5 y) for RANKL, OPG, hsCRP, degradation products of C-terminal
      telopeptides of type I collagen, and osteocalcin. BMD was determined for the
      lumbar spine (L2-L4) and the proximal femur using dual-energy x-ray
      absorptiometry. RESULTS: Circulating levels of OPG (r = 0.30, P < 0.001) and the
      RANKL/OPG ratio (r = -0.17, P < 0.001) were significantly associated with age.
      The geometric mean of hsCRP was 1.89 mg/L (SE, 1.05) in the population studied.
      There was a significant correlation between log(hsCRP) levels and body mass index
      (BMI; r = 0.36, P < 0.001). Multivariate linear analyses revealed that age (beta
      = -0.295, P < 0.001), BMI (beta = 0.464, P < 0.001), RANKL (beta = -0.105, P =
      0.014), and OPG (beta = 0.098, P = 0.029) were the independent determinants for
      lumbar BMD (R(2) = 0.35). Age (beta = -0.250, P < 0.001), BMI (beta = 0.486, P <
      0.001), and RANKL (beta = -0.110, P = 0.009) were independently correlated with
      femoral neck BMD (R(2) = 0.36). Age- and BMI-adjusted analysis by quartiles of
      log-transformed hsCRP did not reveal an association with BMD, serum levels of
      biochemical markers of bone turnover, RANKL, or OPG. CONCLUSIONS: The circulating
      levels of the RANKL/OPG osteoimmunity system have an association with BMD, but
      subclinical systemic inflammation may not be involved in bone mass in healthy
      postmenopausal women.

PMID- 19387416
TI  - Bone mineral density, arterial stiffness, and coronary atherosclerosis in healthy
      postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to assess the correlation between bone
      mineral density (BMD), arterial stiffness, and coronary atherosclerosis in
      healthy postmenopausal women. METHODS: We performed a retrospective review of 152
      postmenopausal women who visited the health promotion center for a routine
      checkup, after excluding participants who had factors affecting BMD and coronary
      artery disease. BMD was evaluated by dual-energy x-ray absorptiometry in the
      lumbar spine and femur. Arterial stiffness was measured by brachial-ankle pulse
      wave velocity (baPWV), and coronary atherosclerosis was assessed by 64-row
      multidetector computed tomography. RESULTS: Women with osteoporosis had a
      significantly higher baPWV than those in the osteopenia and normal BMD groups.
      Higher baPWV was also associated with the presence of atherosclerosis. The baPWV
      was significantly positively correlated with age, systolic blood pressure,
      diastolic blood pressure, and neutrophil to lymphocyte ratio and negatively
      correlated with femur BMD. The optimum predictive value of baPWV in coronary
      atherosclerosis was estimated using the receiver operating characteristic curve.
      A cutoff of 1,506 cm/second would give a sensitivity of 83.3% and specificity of
      82.9%. A higher overall risk for coronary atherosclerosis emerges with higher
      baPWV levels (>1,500 cm/s) after controlling for age and cardiovascular risk
      factors. CONCLUSIONS: Arterial stiffness by measuring baPWV can be a useful
      independent predictor for coronary atherosclerosis. In addition, our results
      suggest that postmenopausal women with osteoporosis should be considered for
      further evaluation of coronary atherosclerosis.

PMID- 19387417
TI  - Type 2 diabetes mellitus and other cardiovascular risk factors are no more common
      during menopause: longitudinal study.
AB  - OBJECTIVE: The aim of this study was to undertake a prospective study of the
      changes in certain risk factors for cardiovascular disease occurring during
      menopause. METHODS: A longitudinal cohort study of 475 women was followed up for
      6 years (Pizarra Study). The final menstrual period was defined after at least 6
      months of amenorrhea. The women were classified into three groups: group 1, no
      menopause at either the first or second study; group 2, no menopause at the first
      study but menopause at the second study (6 y later); and group 3, menopause at
      the first study (and also at the second). The following are the main outcome
      measures used: age; body mass index; waist circumference; waist-to-hip ratio;
      skinfold thickness; arm circumference; intake of macronutrients (quantitative
      questionnaire); systolic and diastolic blood pressures; cholesterol,
      triglycerides; high-density lipoprotein cholesterol; uric acid; homeostasis model
      assessment of insulin resistance; and the prevalence of obesity, hypertension,
      type 2 diabetes mellitus, impaired glucose tolerance, and impaired fasting
      glucose. RESULTS: None of the cardiovascular risk factors studied changed during
      the passage from premenopause to postmenopause, independently of age or physical
      activity. CONCLUSIONS: Menopause is a biological condition of the human species,
      for which has recently received attempts at medicalization that were not always
      justified. If menopause is not accompanied by any other cardiovascular risk
      factor independently of age, the stigma of menopause being considered a risk
      factor should cease. Although the results have the strength of a prospective
      study, the sample size forced us to consider these findings as preliminary.

PMID- 19387418
TI  - Sustained cannabinoid agonist treatment augments CGRP release in a PKA-dependent
      manner.
AB  - Studies have shown that sustained cannabinoid treatment increases the sensitivity
      to painful heat stimuli (thermal hyperalgesia) and innocuous mechanical stimuli
      (tactile allodynia). It has been suggested that augmented release of pain
      neurotransmitters (such as calcitonin gene-related peptide, CGRP) might be
      responsible for this abnormal pain sensitization. We hypothesize that
      intracellular adaptations upon sustained cannabinoid treatment causes augmented
      release of CGRP from primary nociceptors leading to increased pain sensitivity.
      We show that sustained (24 h) cannabinoid agonist [(+)WIN 55,212-2] treatment of
      7-day-old neonatal rat dorsal root ganglion neurons significantly augments basal
      CGRP release from these cells in a protein kinase A-dependent manner. Our results
      indicate that these intracellular compensatory adaptations may play a crucial
      trigger role in further neuronal system adaptations for modulation of pain.

PMID- 19387419
TI  - Effect of SLCO1B1 polymorphism on the plasma concentrations of bile acids and
      bile acid synthesis marker in humans.
AB  - BACKGROUND AND OBJECTIVE: Organic anion transporting polypeptide 1B1 (OATP1B1,
      encoded by SLCO1B1) is a sinusoidal influx transporter of human hepatocytes. Our
      aim was to characterize the role of OATP1B1 in the hepatic uptake of bile acids
      in vivo. METHODS: Fasting blood samples were drawn from 24 healthy volunteers
      with SLCO1B1 c.388AA-c.521TT (*1A/*1A) genotype, eight with c.388GG-c.521TT
      (*1B/*1B) genotype, 24 with c.521TC genotype, and nine with c.521CC genotype.
      Plasma concentrations of 15 endogenous bile acids, their synthesis marker, and
      cholesterol were determined by liquid chromatography-tandem mass spectrometry.
      RESULTS: The concentrations of ursodeoxycholic acid, glycoursodeoxycholic acid,
      chenodeoxycholic acid, and glycochenodeoxycholic acid were approximately 50-240%
      higher in individuals with the SLCO1B1 c.521CC, c.521TC, or c.388AA-c.521TT
      genotype than in those with the c.388GG-c.521TT genotype (P<0.05), with the
      largest differences seen between the c.521CC and c.388GG-c.521TT individuals. The
      concentration of tauroursodeoxycholic acid was approximately 120% higher in
      individuals with the c.521TC genotype and that of taurochenodeoxycholic acid 110%
      higher in individuals with the c.521CC or c.521TC genotype than in those with the
      c.388GG-c.521TT genotype (P<0.05). The cholic acid concentration was
      approximately 30% higher in individuals with the c.521CC or c.388AA-c.521TT
      genotype than in those with the c.388GG-c.521TT genotype (P<0.05), but its
      conjugates remained unaffected by the genotype. The bile acid synthesis marker
      7alpha-hydroxy-4-cholesten-3-one/cholesterol concentration ratio was 62 or 45%
      higher in the c.388AA-c.521TT participants than in the c.388GG-c.521TT or c.521TC
      participants, respectively (P<0.05). CONCLUSION: SLCO1B1 polymorphism
      considerably affects the disposition of several endogenous bile acids and bile
      acid synthesis marker, indicating that OATP1B1 plays an important role in the
      hepatic uptake of bile acids in vivo in humans.

PMID- 19387420
TI  - Evaluation of immunoglobulin M and G Western blot and ELISA for screening
      antibodies to Treponema pallidum in blood donors.
AB  - BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) is the most popular method
      used by blood banks in China to screen for antibodies to Treponema pallidum (TP).
      However, this method produces a high percentage of false-positive reactions.The
      current study aimed to propose a more effective procedure for screening anti-TP
      antibodies in blood donors. METHODS: A total of 1009 serum samples showing repeat
      reactivity in routine blood bank procedures were tested with a TP particle
      agglutination assay (TPPA) and 3 commercially available ELISA tests. Samples
      showing reactivity with any of these methods were further tested by Western blot
      (WB) and ELISA immunoglobulin G (IgG)and immunoglobulin M (IgM) anti-TP assays.
      RESULTS: Of the 1009 samples tested, 170 were identified as reactive with at
      least one of our methods. In these 170 samples, excluding borderline cases, the
      agreement of the WB method with TPPA, Murex, BGI, and InTec ELISA tests was
      76.0%, 77.8%, 78.4%, and 80.1%, respectively. With the WB results as the
      reference, the sensitivity of TPPA, Murex, BGI, and InTec ELISA tests was 91.5%,
      95.4%, 99.2%, and 98.5%, respectively. TpN17 and TpN15 are the most important
      antigens in the antibody response of IgM and IgG, respectively. The WB IgM and
      IgG results suggest that the seroprevalence of anti-TP in blood donors in China
      is 0.49% (130/26,702). CONCLUSIONS: A combination of routine ELISA methods and WB
      IgM and IgG may be a valid procedure for the confirmatory testing of anti-TP
      antibodies and would be beneficial for screening blood donors.

PMID- 19387421
TI  - Sexually transmitted infections among patients with acute HIV in North Carolina.

PMID- 19387422
TI  - Micro-drive array for chronic in vivo recording: tetrode assembly.
AB  - The tetrode, a bundle of four electrodes, has proven to be a valuable tool for
      the simultaneous recording of multiple neurons in-vivo. The differential
      amplitude of action potential signatures over the channels of a tetrode allows
      for the isolation of single-unit activity from multi-unit signals. The ability to
      precisely control the stereotaxic location and depth of the tetrode is critical
      for studying coordinated neural activity across brain regions. In combination
      with a micro-drive array, it is possible to achieve precise placement and stable
      control of many tetrodes over the course of days to weeks. In this protocol, we
      demonstrate how to fabricate and condition tetrodes using basic tools and
      materials, install the tetrodes into a multi-drive tetrode array for chronic in
      vivo recording in the rat, make ground wire connections to the micro-drive array,
      and attach a protective cone onto the micro-drive array in order to protect the
      tetrodes from physical contact with the environment.

PMID- 19387423
TI  - Attention deficits and hyperactivity following inhibition of cAMP-dependent
      protein kinase within the medial prefrontal cortex of rats.
AB  - Previous work demonstrates that microinjections of dopamine D1 receptor agonists
      and antagonists directly into the medial prefrontal cortex (mPFC) of rats can
      affect attention in the 5-choice serial reaction time task (5CSRTT), a rodent
      test analogous to the continuous performance task used to study attention in
      humans. These studies were designed to determine if intra-mPFC modulation of cAMP
      dependent protein kinase (PKA), an intracellular target of D1 receptor
      stimulation, also affects attention. We examined the effects of localized
      microinfusions of the cAMP analog Sp-cAMPS (to activate PKA) or Rp-cAMPS (to
      inhibit PKA) in the 5CSRTT. In parallel, we examined the effects of these
      manipulations on activity levels in an open field, as well as on motivation and
      the capacity to make complex operant responses using the intracranial self
      stimulation (ICSS) test. Inhibition of PKA reduced accuracy in the 5CSRTT and
      caused substantial increases in locomotor activity without affecting motivation
      or the capacity to emit operant responses at high rates. Stimulation of PKA also
      affected some measures of performance in the 5CSRTT, but this effect was
      associated with reduced capacity to respond at high rates. Viral vector-mediated
      disruption of cAMP response element-binding protein (CREB), a transcription
      factor directly activated by PKA, also reduced accuracy in the 5CSRTT, raising
      the possibility that acute inhibition of PKA and sustained inhibition of CREB
      affect attention through common mechanisms. These studies indicate that PKA
      inhibition within the mPFC of rats produces inattention and hyperactivity, and
      thus might be useful in modeling human attention disorders.

PMID- 19387424
TI  - A haplotype of the norepinephrine transporter (Net) gene Slc6a2 is associated
      with clinical response to atomoxetine in attention-deficit hyperactivity disorder
      (ADHD).
AB  - Atomoxetine is a specific inhibitor of the norepinephrine transporter (NET) that
      has demonstrated efficacy in the treatment of children with attention-deficit
      hyperactivity disorder (ADHD). We investigated whether polymorphisms in the
      NET/SLC6A2 gene may influence atomoxetine response in ADHD. Two independent
      cohorts of 160 and 105 ADHD children treated for 6 weeks with atomoxetine (0.5
      1.8 mg/kg per day) were genotyped on CYP2D6, which metabolizes atomoxetine, and
      108 single nucleotide polymorphisms in the NET/SLC6A2 gene. Response was defined
      as a minimum decrease of 25% in ADHD Rating Scale IV-Parent Version and a
      Clinical Global Impression-Severity (CGI-S) score less than or equal to 2 at week
      6. Interindividual response was independent of the genetic variants of CYP2D6.
      Significant (p<0.05) associations between 20 NET/SLC6A2 single nucleotide
      polymorphisms (SNPs) and clinical efficacy in atomoxetine responders, compared
      with non-responders, were observed. The genomic region across exons 4 to 9 of
      NET/SLC6A2, where 36 SNPs have been genotyped, was associated with treatment
      response in both cohorts (p<0.01, odds ratio=2.2 and p=0.026, odds ratio=6.3,
      respectively), in the combined cohort (p<0.01, odds ratio=1.83), and in the
      subgroup of Caucasians only (p=0.02, odds ratio=1.8). Clinical efficacy of
      atomoxetine treatment in ADHD shows potential dependence upon a series of genetic
      polymorphisms of its mechanistic target, the norepinephrine transporter. Taking
      into account the high heritability of ADHD, the significance of the present
      finding and replication of a similar haplotype allele sequence result in an
      independent cohort, it is suggested that further assessment of this region could
      be useful in determining response to atomoxetine in ADHD.

PMID- 19387426
TI  - Treating heart rate for the prevention of diabetes: the next step?

PMID- 19387427
TI  - Might a leptin gene variant affect blood pressure in obese brazilians?

PMID- 19387428
TI  - Masked hypertension in children and adolescents.

PMID- 19387429
TI  - Link between macrocirculation and microcirculation in isolated systolic
      hypertension of older subjects.

PMID- 19387430
TI  - NO-independent activators of soluble guanylate cyclase: therapeutic potential.

PMID- 19387431
TI  - Acute sodium loading in Dahl-s rats: alterations in renal and vascular sodium
      pump inhibition amidst unaltered cardiotonic steroid levels?

PMID- 19387432
TI  - Thiazide-induced hyperglycemia: can it be prevented?

PMID- 19387434
TI  - Modeling and simulation of the time course of asenapine exposure response and
      dropout patterns in acute schizophrenia.
AB  - Modeling and simulation were utilized to characterize the efficacy dose response
      of sublingual asenapine in patients with schizophrenia and to understand the
      outcomes of six placebo-controlled trials in which placebo responses and dropout
      rates varied. The time course of total Positive and Negative Syndrome Scale
      (PANSS) scores was characterized for placebo and asenapine treatments in a
      pharmacokinetic-pharmacodynamic model in which the asenapine effect was described
      by an E(max) model, increasing linearly over the 6-week study period. A logistic
      regression model described the time course of dropouts, with previous PANSS value
      being the most important predictor. The last observation carried forward (LOCF)
      time courses were well described in simulations from the combined PANSS + dropout
      model. The observed trial outcomes were successfully predicted for all the
      placebo arms and the majority of the treatment arms. Although simulations
      indicated that the post hoc probability of success of the performed trials was
      low to moderate, these analyses demonstrated that 5 and 10 mg twice-daily
      (b.i.d.) doses of asenapine have similar efficacy.

PMID- 19387433
TI  - Intestinal epithelial cells promote colitis-protective regulatory T-cell
      differentiation through dendritic cell conditioning.
AB  - Intestinal dendritic cells (DCs) have been shown to display specialized
      functions, including the ability to promote gut tropism to lymphocytes, to
      polarize noninflammatory responses, and to drive the differentiation of adaptive
      Foxp3(+) regulatory T (T(reg)) cells. However, very little is known about what
      drives the mucosal phenotype of DCs. Here, we present evidence that the local
      microenvironment, and in particular intestinal epithelial cells (ECs), drive the
      differentiation of T(reg)-cell-promoting DCs, which counteracts Th1 and Th17
      development. EC-derived transforming growth factor-beta (TGF-beta) and retinoic
      acid (RA), but not thymic stromal lymphopoietin (TSLP), were found to be required
      for DC conversion. After EC contact, DCs upregulated CD103 and acquired a
      tolerogenic phenotype. EC-conditioned DCs were capable of inducing de novo T(reg)
      cells with gut-homing properties that when adoptively transferred, protected mice
      from experimental colitis. Thus, we have uncovered an essential mechanism in
      which EC control of DC function is required for tolerance induction.

PMID- 19387435
TI  - Availability of medical countermeasures for bioterrorism events: US legal and
      regulatory options.

PMID- 19387436
TI  - Biomarker discovery: identification of a growth factor gene signature.
AB  - Gene expression signatures can be developed as comprehensive pathway readouts and
      used as pharmacodynamic or patient-stratification biomarkers. While a consensus
      on the best practices for selecting gene expression signatures from microarray
      data is evolving, we have developed basic guidelines to ensure consistency and
      quality. Here we illustrate these guidelines through the identification of a
      growth factor gene expression signature that is responsive to
      phosphatidylinositol 3-kinase (PI3K) pathway perturbations in vitro and related
      to phosphatase and tensin homolog (PTEN) deregulation in vivo.

PMID- 19387437
TI  - Mechanistic modeling of a magnetic marker monitoring study linking
      gastrointestinal tablet transit, in vivo drug release, and pharmacokinetics.
AB  - Magnetic marker monitoring (MMM) is a new technique for visualizing transit and
      disintegration of solid oral dosage forms through the gastrointestinal (GI)
      tract. The aim of this work was to develop a modeling approach for gaining
      information from MMM studies using data from a food interaction study with
      felodipine extended-release (ER) formulation. The interrelationship between
      tablet location in the GI tract, in vivo drug release, and felodipine disposition
      was modeled. A Markov model was developed to describe the tablet's movement
      through the GI tract. Tablet location within the GI tract significantly affected
      drug release and absorption through the gut wall. Food intake decreased the
      probability of tablet transition from the stomach, decreased the rate with which
      released felodipine left the stomach, and increased the fraction absorbed across
      the gut wall. In conclusion, the combined information of tablet location in the
      GI tract, in vivo drug release, and plasma concentration can be utilized in a
      mechanistically informative way with integrated modeling of data from MMM
      studies.

PMID- 19387438
TI  - NAADP mobilizes calcium from acidic organelles through two-pore channels.
AB  - Ca(2+) mobilization from intracellular stores represents an important cell
      signalling process that is regulated, in mammalian cells, by inositol-1,4,5
      trisphosphate (InsP(3)), cyclic ADP ribose and nicotinic acid adenine
      dinucleotide phosphate (NAADP). InsP(3) and cyclic ADP ribose cause the release
      of Ca(2+) from sarcoplasmic/endoplasmic reticulum stores by the activation of
      InsP(3) and ryanodine receptors (InsP(3)Rs and RyRs). In contrast, the nature of
      the intracellular stores targeted by NAADP and the molecular identity of the
      NAADP receptors remain controversial, although evidence indicates that NAADP
      mobilizes Ca(2+) from lysosome-related acidic compartments. Here we show that two
      pore channels (TPCs) comprise a family of NAADP receptors, with human TPC1 (also
      known as TPCN1) and chicken TPC3 (TPCN3) being expressed on endosomal membranes,
      and human TPC2 (TPCN2) on lysosomal membranes when expressed in HEK293 cells.
      Membranes enriched with TPC2 show high affinity NAADP binding, and TPC2 underpins
      NAADP-induced Ca(2+) release from lysosome-related stores that is subsequently
      amplified by Ca(2+)-induced Ca(2+) release by InsP(3)Rs. Responses to NAADP were
      abolished by disrupting the lysosomal proton gradient and by ablating TPC2
      expression, but were only attenuated by depleting endoplasmic reticulum Ca(2+)
      stores or by blocking InsP(3)Rs. Thus, TPCs form NAADP receptors that release
      Ca(2+) from acidic organelles, which can trigger further Ca(2+) signals via
      sarcoplasmic/endoplasmic reticulum. TPCs therefore provide new insights into the
      regulation and organization of Ca(2+) signals in animal cells, and will advance
      our understanding of the physiological role of NAADP.

PMID- 19387439
TI  - Formyl peptide receptor-like proteins are a novel family of vomeronasal
      chemosensors.
AB  - Mammals rely heavily on olfaction to interact adequately with each other and with
      their environment. They make use of seven-transmembrane G-protein-coupled
      receptors to identify odorants and pheromones. These receptors are present on
      dendrites of olfactory sensory neurons located in the main olfactory or
      vomeronasal sensory epithelia, and pertain to the odorant, trace amine-associated
      receptor and vomeronasal type 1 (ref. 4) or 2 (refs 5-7) receptor superfamilies.
      Whether these four sensor classes represent the complete olfactory molecular
      repertoire used by mammals to make sense of the outside world is unknown. Here we
      report the expression of formyl peptide receptor-related genes by vomeronasal
      sensory neurons, in multiple mammalian species. Similar to the four known
      olfactory receptor gene classes, these genes encode seven-transmembrane proteins,
      and are characterized by monogenic transcription and a punctate expression
      pattern in the sensory neuroepithelium. In vitro expression of mouse formyl
      peptide receptor-like 1, 3, 4, 6 and 7 provides sensitivity to
      disease/inflammation-related ligands. Establishing an in situ approach that
      combines whole-mount vomeronasal preparations with dendritic calcium imaging in
      the intact neuroepithelium, we show neuronal responses to the same molecules,
      which therefore represent a new class of vomeronasal agonists. Taken together,
      these results suggest that formyl peptide receptor-like proteins have an
      olfactory function associated with the identification of pathogens, or of
      pathogenic states.

PMID- 19387440
TI  - Irreversibility of mitotic exit is the consequence of systems-level feedback.
AB  - The eukaryotic cell cycle comprises an ordered series of events, orchestrated by
      the activity of cyclin-dependent kinases (Cdks), leading from chromosome
      replication during S phase to their segregation in mitosis. The unidirectionality
      of cell-cycle transitions is fundamental for the successful completion of this
      cycle. It is thought that irrevocable proteolytic degradation of key cell-cycle
      regulators makes cell-cycle transitions irreversible, thereby enforcing
      directionality. Here we have experimentally examined the contribution of cyclin
      proteolysis to the irreversibility of mitotic exit, the transition from high
      mitotic Cdk activity back to low activity in G1. We show that forced cyclin
      destruction in mitotic budding yeast cells efficiently drives mitotic exit
      events. However, these remain reversible after termination of cyclin proteolysis,
      with recovery of the mitotic state and cyclin levels. Mitotic exit becomes
      irreversible only after longer periods of cyclin degradation, owing to activation
      of a double-negative feedback loop involving the Cdk inhibitor Sic1 (refs 4, 5).
      Quantitative modelling suggests that feedback is required to maintain low Cdk
      activity and to prevent cyclin resynthesis. Our findings demonstrate that the
      unidirectionality of mitotic exit is not the consequence of proteolysis but of
      systems-level feedback required to maintain the cell cycle in a new stable state.

PMID- 19387443
TI  - Challenges for science in India.

PMID- 19387444
TI  - India's rocky road to scientific success. Interview by Joerg Heber.

PMID- 19387446
TI  - Nanoparticle assembly: DNA provides control.

PMID- 19387447
TI  - Nanocapacitors: undead layers breathe new life.

PMID- 19387448
TI  - Quantum information: Mother Nature outgrown.

PMID- 19387449
TI  - Hydrogels: Gene jelly.

PMID- 19387450
TI  - Material witness: Superconducting when wet.

PMID- 19387451
TI  - Surface water: Pentagonal ice in chains.

PMID- 19387452
TI  - Superconducting group-IV semiconductors.
AB  - Despite the amount of experimental and theoretical work on doping-induced
      superconductivity in covalent semiconductors based on group IV elements over the
      past four years, many open questions and puzzling results remain to be clarified.
      The nature of the coupling (whether mediated by electronic correlation, phonons
      or both), the relationship between the doping concentration and the critical
      temperature (T(c)), which affects the prospects for higher transition
      temperatures, and the influence of disorder and dopant homogeneity are debated
      issues that will determine the future of the field. Here, we present recent
      achievements and predictions, with a focus on boron-doped diamond and silicon. We
      also suggest that innovative superconducting devices, combining specific
      properties of diamond or silicon with the maturity of semiconductor-based
      technologies, will soon be developed.

PMID- 19387453
TI  - Isolated elevated blood neutrophil concentration at altitude does not require
      NICU admission if appropriate reference ranges are used.
AB  - OBJECTIVE: The Intermountain Healthcare hospitals use a clinical pathway
      algorithm for early-onset infection, which is based on the 2002 Centers for
      Disease Control and Prevention (CDC) guidelines for perinatal group B
      streptococcal disease. As part of this pathway, neonates in the well baby
      nursery, who seem to be well but have risk factors for infection, receive a
      'limited laboratory evaluation including a CBC', and if the complete blood cell
      count (CBC) is abnormal, antibiotic treatment and neonatal intensive care unit
      (NICU) monitoring are initiated. We recently found that reference ranges for
      absolute neutrophil counts (ANCs) are much wider at our altitude (4800 to 5000
      ft) than at sea level. On this basis, we speculated that some well babies with
      risk factors for infection are mistakenly judged as having an abnormal CBC, and
      are unnecessarily admitted to the NICU. STUDY DESIGN: This was a retrospective
      observational cohort study of neonates of >37 weeks gestation admitted to either
      of two Intermountain Healthcare NICUs for intravenous antibiotic treatment during
      a recent 36-month period. RESULTS: During the study period 3217 patients were
      admitted to the two NICUs, 1049 (32.6%) of which were born at>37 weeks gestation.
      Of these, 14 (1.3%) were found to have been admitted to the NICU on the basis of
      an abnormal CBC (elevated ANC), when in retrospect, using the appropriate ANC
      chart, their CBCs were completely normal. None of the 14 neonates had a leukocyte
      left shift (immature to total neutrophil ratio >0.3) or thrombocytopenia. None
      were treated with supplemental oxygen or mechanical ventilation in the NICU. All
      14 had sterile blood cultures. All had antibiotics stopped in 48 to 72 h, and all
      were discharged home as well babies. CONCLUSION: We identified 14 neonates who,
      while in the well baby nursery, were found to have risk factors for early-onset
      infection, but did not seem to be infected, and were subsequently admitted to a
      NICU for intravenous antibiotic treatment and monitoring under the mistaken
      impression that they had an abnormal CBC. We maintain that use of an appropriate
      neutrophil reference range chart can reduce NICU admissions and can limit
      unnecessary antibiotic exposure.

PMID- 19387454
TI  - Erectile dysfunction and heart failure: the role of phosphodiesterase type 5
      inhibitors.
AB  - The phosphodiesterase type 5 (PDE-5) inhibitors are effective in treating
      erectile dysfunction (ED). ED and heart failure (HF) share similar risk factors,
      and commonly present together. This association has led to questions ranging from
      the safety and efficacy of PDE-5 inhibitors in HF patients to a possible role for
      this class of medication to treat HF patients with or without ED. In addition to
      endothelial dysfunction, there are causes of ED specific to patients with HF
      including low exercise tolerance, depression and HF medications. Before treating
      HF patients with PDE-5 inhibitors, patients should be assessed for their risk of
      a cardiac event during sexual activity. PDE-5 inhibitors are safe and effective
      in treating ED in HF patients. An improvement in erectile function by PDE-5
      inhibitors was associated with an improvement in quality of life and reduction in
      depression. Several studies demonstrated the effect of PDE-5 inhibitors on HF per
      se. PDE-5 inhibitors improved endothelial dysfunction, increased exercise
      tolerance, decreased pulmonary vascular resistance and pulmonary artery pressure,
      and increased cardiac index. Several mechanisms whereby PDE-5 inhibitors improve
      HF have been proposed. PDE-5 inhibitors already have a role in treating primary
      pulmonary hypertension; however additional studies are needed to determine if
      they will become a standard therapy for HF patients.

PMID- 19387455
TI  - Functional analysis of -351 interleukin-9 promoter polymorphism reveals an
      activator controlled by NF-kappaB.
AB  - Genetic studies have shown linkages for asthma to the chromosomal region 5q31-q33
      in humans that includes the IL-9 gene. An A-to-G base substitution has been
      identified at bp -351 in the IL-9 promoter. The role of this polymorphism in IL-9
      promoter function was assessed utilizing CD4+ T cells purified from individuals
      with one or two of the G alleles in comparison to those homozygous for the wild
      type A. The presence of an A at -351 (A allele) increased mitogen-stimulated IL-9
      transcription twofold in comparison to subjects with one or two G alleles at this
      position. Binding of nuclear extract proteins from IL-9-producing human cell
      lines to DNA sequences including this base exchange demonstrated specific binding
      of the transcription factor NF-kappaB. Binding of NF-kappaB to the IL-9 promoter
      was confirmed in vivo using the chromatin immunoprecipitation assay. Recombinant
      NF-kappaB bound to a promoter fragment with the A allele with fivefold higher
      affinity than it did to a promoter with the G allele. Individuals carrying the A
      allele of the IL-9 promoter display increased synthesis of IL-9, which may result
      in strong Th2 immune responses and a modulation of their susceptibility to
      infectious, neoplastic, parasitic or atopic disease.

PMID- 19387456
TI  - Meta-analysis and imputation identifies a 109 kb risk haplotype spanning TNFAIP3
      associated with lupus nephritis and hematologic manifestations.
AB  - TNFAIP3 encodes the ubiquitin-modifying enzyme, A20, a key regulator of
      inflammatory signaling pathways. We previously reported association between
      TNFAIP3 variants and systemic lupus erythematosus (SLE). To further localize the
      risk variant(s), we performed a meta-analysis using genetic data available from
      two Caucasian case-control datasets (1453 total cases, 3381 total control
      subjects) and 713 SLE trio families. The best result was found at rs5029939
      (P=1.67 x 10(-14), odds ratio=2.09, 95% confidence interval 1.68-2.60). We then
      imputed single nucleotide polymorphisms (SNPs) from the CEU Phase II HapMap using
      genotypes from 431 SLE cases and 2155 control subjects. Imputation identified 11
      SNPs in addition to three observed SNPs, which together, defined a 109 kb SLE
      risk segment surrounding TNFAIP3. When evaluating whether the rs5029939 risk
      allele was associated with SLE clinical manifestations, we observed that
      heterozygous carriers of the TNFAIP3 risk allele at rs5029939 have a twofold
      increased risk of developing renal or hematologic manifestations compared to
      homozygous non-risk subjects. In summary, our study strengthens the genetic
      evidence that variants in the region of TNFAIP3 influence risk for SLE,
      particularly in patients with renal and hematologic manifestations, and narrows
      the risk effect to a 109 kb DNA segment that spans the TNFAIP3 gene.

PMID- 19387457
TI  - Association of UCP2 -866 G/A polymorphism with chronic inflammatory diseases.
AB  - We reported earlier that two mitochondrial gene polymorphisms, UCP2 -866 G/A
      (rs659366) and mtDNA nt13708 G/A (rs28359178), are associated with multiple
      sclerosis (MS). Here we aim to investigate whether these functional polymorphisms
      contribute to other eight chronic inflammatory diseases, including rheumatoid
      arthritis (RA), systemic lupus erythematosus (SLE), Wegener' granulomatosis (WG),
      Churg-Strauss syndrome (CSS), Crohn's disease (CD), ulcerative colitis (UC),
      primary sclerosing cholangitis (PSC) and psoriasis. Compared with individual
      control panels, the UCP2 -866 G/A polymorphism was associated with RA and SLE,
      and the mtDNA nt13708 G/A polymorphism with RA. Compared with combined controls,
      the UCP2 -866 G/A polymorphism was associated with SLE, WG, CD and UC. When all
      eight disease panels and the original MS panel were combined in a meta-analysis,
      the UCP2 was associated with chronic inflammatory diseases in terms of either
      alleles (odds ratio (OR)=0.91, 95% confidence interval (95% CI): 0.86-0.96),
      P=0.0003) or genotypes (OR=0.88, (95% CI: 0.82-0.95), P=0.0008), with the -866A
      allele associated with a decreased risk to diseases. As the -866A allele
      increases gene expression, our findings suggest a protective role of the UCP2
      protein in chronic inflammatory diseases.

PMID- 19387458
TI  - Complement receptor 2 polymorphisms associated with systemic lupus erythematosus
      modulate alternative splicing.
AB  - Genetic factors influence susceptibility to systemic lupus erythematosus (SLE). A
      recent family-based analysis in Caucasian and Chinese populations provided
      evidence for association of single-nucleotide polymorphisms (SNPs) in the
      complement receptor 2 (CR2/CD21) gene with SLE. Here we confirmed this result in
      a case-control analysis of an independent European-derived population including
      2084 patients with SLE and 2853 healthy controls. A haplotype formed by the minor
      alleles of three CR2 SNPs (rs1048971, rs17615, rs4308977) showed significant
      association with decreased risk of SLE (30.4% in cases vs 32.6% in controls,
      P=0.016, OR=0.90 (0.82-0.98)). Two of these SNPs are in exon 10, directly 5' of
      an alternatively spliced exon preferentially expressed in follicular dendritic
      cells (FDC), and the third is in the alternatively spliced exon. Effects of these
      SNPs and a fourth SNP in exon 11 (rs17616) on alternative splicing were
      evaluated. We found that the minor alleles of these SNPs decreased splicing
      efficiency of exon 11 both in vitro and ex vivo. These findings further implicate
      CR2 in the pathogenesis of SLE and suggest that CR2 variants alter the
      maintenance of tolerance and autoantibody production in the secondary lymphoid
      tissues where B cells and FDCs interact.

PMID- 19387459
TI  - Admixture in Hispanic Americans: its impact on ITGAM association and implications
      for admixture mapping in SLE.
AB  - Systemic Lupus Erythematosus (SLE) disproportionately affects minorities, such as
      Hispanic Americans (HA). Prevalence of SLE is 3-5 times higher in HA than in
      European-derived populations and have more active disease at the time of
      diagnosis, with more serious organ system involvement. HA is an admixed
      population, it is possible that there is an effect of admixture on the relative
      risk of the disease. This admixture can create substantial increase of linkage
      disequilibrium (LD) in both magnitude and range, which can provide a unique
      opportunity for admixture mapping. The main objectives of this study are to (a)
      estimate hidden population structure in HA individuals; (b) estimate individual
      ancestry proportions and its impact on SLE risk; (c) assess impact of admixture
      on ITGAM association, a recently identified SLE susceptibility gene; and (d)
      estimate power of admixture mapping in HA. Our dataset contained 1125
      individuals, of whom 884 (657 SLE cases and 227 controls) were self-classified as
      HA. Using 107 unlinked ancestry informative markers (AIMs), we estimated hidden
      population structure and individual ancestry in HA. Out of 5671 possible pairwise
      LD, 54% were statistically significant, indicating recent population admixture.
      The best-fitted model for HA was a four-population model with average ancestry of
      European (48%), American-Indian (AI) (40%), African (8%) and a fourth population
      (4%) with unknown ancestry. We also identified significant higher risk associated
      with AI ancestry (odds ratio (OR)=4.84, P=0.0001, 95% CI (confidence
      interval)=2.14-10.95) on overall SLE. We showed that ITGAM is associated as a
      risk factor for SLE (OR=2.06, P=8.74 x 10(-5), 95% CI=1.44-2.97). This
      association is not affected by population substructure or admixture. We have
      shown that HA have great potential and are an appropriate population for
      admixture mapping. As expected, the case-only design is more powerful than case
      control design, for any given admixture proportion or ancestry risk ratio.

PMID- 19387460
TI  - Adaptive evolution of interferon-gamma in Glire lineage and evidence for a recent
      selective sweep in Mus. m. domesticus.
AB  - Interferon-gamma plays a key role in the immune response against intracellular
      pathogens. Its gene is located inside a cluster of cytokines from the interleukin
      10 family. A comparison of the coding sequences in the mammalian Glire lineage
      indicates a possible action of positive Darwinian selection promoting rapid amino
      acid changes in the branch leading to murine rodents represented by Mus and
      Rattus. Looking at genomic diversity of this gene inside the genus Mus, we could
      propose that a recent selective sweep has affected M. m. domesticus, this
      subspecies harbouring predominantly a single Ifng haplotype that differs from
      that of the other subspecies by a unique amino-acid difference in a key position
      of the molecule. The sweep seems to have affected a region of at most 50 kb as
      recombinants could be found at flanking conserved non-coding sequences.
      Functional differences were clearly apparent in cis-regulation of Ifng
      transcription between the domesticus and the musculus-type haplotypes. As the
      presence of the musculus haplotype in a predominantly domesticus background seems
      to promote susceptibility to chronic infection by Theiler's virus, these findings
      open interesting avenues for documenting immune system gene co-evolution.

PMID- 19387462
TI  - The heritability and genetics of complement C3 expression in UK SLE families.
AB  - As the central component of the complement system, C3 has sensory and effector
      functions bridging innate and adaptive immunity. It is plausible that common
      genetic variation at C3 determines either serum C3 level or susceptibility to
      systemic lupus erythematosus (SLE), but only a single, Japanese, study has
      currently showed genetic association. In a cohort of 1371 individuals from 393 UK
      white European SLE families, we quantified serum C3 and genotyped C3 tagSNPs.
      Using a Bayesian variance components model, we estimated 39.6% serum C3
      heritability. Genotype/serum C3 association was determined by mixed linear
      models. Single nucleotide polymorphism (SNP) rs344555, located in a haplotype
      block incorporating the 3' end of C3, was associated with serum C3 (P=0.007),
      with weaker associations observed for other SNPs in this block. In an extended
      cohort of 585 SLE families the association between C3 variants and SLE was
      assessed by transmission disequilibrium test. SNP rs3745568 was associated with
      SLE (P=0.0046), but not with serum C3. Our disease associated SNP differs from
      that highlighted in the Japanese study; however, we replicate their finding that
      genetic variants at the 3' end of C3 are associated with serum C3. Larger studies
      and further fine mapping will be required to definitively identify functional
      variants.

PMID- 19387461
TI  - Interleukin-6 haplotypes and the response to therapy of chronic hepatitis C virus
      infection.
AB  - Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals
      worldwide. Treatment of HCV with pegylated interferon-alpha-2a is successful in
      eradicating virus from only 30 to 80% of those treated. Interleukin-6 (IL-6) is
      an important cytokine involved in the immune response to infectious agents and in
      vitro studies suggest that host genetic variation, particularly haplotypes, may
      affect IL-6 expression. We examined the contribution of haplotypes in the IL-6
      gene on sustained viral response (SVR) to the therapy for chronic HCV infection.
      We observed the IL-6 T-T-G-G-G-G-C-A-G-A haplotype to be associated with a lower
      risk of achieving SVR among Caucasian Americans (CAs) ((relative risk) RR=0.80;
      95% CI: 0.66-0.98; P=0.0261). Using a sliding window approach, the rs1800797-(G)
      rs1800796-(G)-rs1800795-(G) haplotype was associated with a reduced chance of SVR
      (RR=0.79; 95% CI: 0.66-0.94; P=0.0081), as was the rs1800796-(G)-rs1800795-(G)
      rs2069830-(C) haplotype (RR=0.78; 95% CI: 0.66-0.94; P=0.0065) among CAs.
      Overall, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was
      independently associated with a reduced chance of SVR (RR=0.78; 95% CI: 0.62-1.0;
      P=0.0489) after adjustment for potential confounding factors. Our findings
      further illustrate the complexity of IL-6 genetic regulation and the potential
      importance of haplotypes on IL-6 expression. Our findings provide additional
      support for the potential importance of genetic variation in the IL-6 gene and
      the response to HCV therapy.

PMID- 19387463
TI  - Variation in the ATP-binding cassette transporter 2 gene is a separate risk
      factor for systemic lupus erythematosus within the MHC.
AB  - The ATP-binding cassette transporter (TAP) proteins are functionally relevant
      candidates for predisposition to systemic lupus erythematosus (SLE) by virtue of
      their role in autoantigen presentation and location in the major
      histocompatibility complex (MHC). We tested if variation in the TAP genes (TAP1
      and TAP2) is associated with SLE. We genotyped tag single nucleotide
      polymorphisms (SNPs) and performed family-based association analysis on 390
      Caucasian pedigrees. We found significant evidence of association between TAP2
      and SLE (rs241453, P=1.33 x 10(-6)). Conditional logistic regression analysis
      suggests that this TAP2 effect is separate from the HLA-DRB1 alleles. Our
      analyses show that both rs241453 (P=1.6 x 10(-4)) and HLA-DRB1*03xx (P=2.3 x 10(
      4)) have significant autonomous effects not due to linkage disequilibrium.
      Moreover, these loci exhibit a significant statistical interaction (P<1.0 x 10(
      6)), demonstrated by an increase in the odds ratio for the TAP2 association from
      OR=2.00 (95% confidence interval (CI)=1.17-3.42) in HLA-DRB1*03xx-negative
      subjects to OR=4.29 (CI=1.88-9.76) in the subjects with at least one HLA
      DRB1*03xx allele group. We report the largest association study of the TAP genes
      with SLE to date, and the first to test for its separate effect and interaction
      with the HLA alleles consistently associated with SLE.

PMID- 19387464
TI  - Wnt signaling pathway is epigenetically regulated by methylation of Wnt
      antagonists in acute myeloid leukemia.
AB  - Activation of the Wnt signaling pathway has been implicated recently in the
      pathogenesis of leukemia. We studied the function of epigenetic regulation of the
      Wnt pathway and its prognostic relevance in acute myelogenous leukemia (AML). We
      used a methylation-specific polymerase chain reaction approach to analyze the
      promoter methylation status of a panel of Wnt antagonists including sFRP1, sFRP2,
      sFRP4, sFRP5, DKK1 and DKK3. Aberrant methylation of Wnt antagonists was detected
      in four AML cell lines and in up to 64% of AML marrow samples. Treatment of the
      cell lines with 5-aza-2'-deoxycytidine induced reexpression of methylated Wnt
      antagonists and inactivation of the Wnt pathway by downregulating the Wnt pathway
      genes cyclin D1, TCF1 and LEF1 and reducing nuclear localization of beta-catenin.
      In a subgroup of patients 60 years and younger with newly diagnosed AML and
      intermediate-risk cytogenetics, abnormal methylation of Wnt antagonists was
      associated with decreased 4-year relapse-free survival (28 vs 61%, respectively,
      P=0.03). Our results indicate a function of the epigenetic regulation of the Wnt
      pathway in predicting relapse in a subgroup of AML patients.

PMID- 19387465
TI  - A novel pedigree with heterozygous germline RUNX1 mutation causing familial MDS
      related AML: can these families serve as a multistep model for leukemic
      transformation?

PMID- 19387466
TI  - Involvement of mast cells by the malignant process in patients with Philadelphia
      chromosome negative myeloproliferative neoplasms.
AB  - The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) are
      clonal hematologic malignancies frequently characterized by a mutation in JAK2
      (JAK2V617F). Peripheral blood (PB) CD34(+) cells from patients with polycythemia
      vera (PV) and primary myelofibrosis (PMF) generated in vitro significantly fewer
      mast cells (MCs) than normal PB CD34(+) cells. The numbers of MC progenitors
      assayed from MPN CD34(+) cells were, however, similar to that assayed from normal
      CD34(+) cells. A higher percentage of the cultured MPN MCs expressed
      FcvarepsilonRIalpha, CD63 and CD69 than normal MCs, suggesting that cultured MPN
      MCs are associated with an increased state of MC activation. Further analysis
      showed that a higher proportion of cultured PV and PMF MCs underwent apoptosis in
      vitro. By using JAK2V617F, MplW515L and chromosomal abnormalities as clonality
      markers, we showed that the malignant process involved MPN MCs. JAK2V617F
      positive MC colonies were assayable from the PB CD34(+) cells of each of the 17
      JAK2V617F positive MPN patients studied. Furthermore, erlotinib, a JAK2
      inhibitor, was able to inhibit JAK2V617F-positive PV MC progenitor cells,
      indicating that malignant MC progenitor cells are a potential cellular target for
      such JAK2 inhibitor-directed therapy.

PMID- 19387467
TI  - Flow cytometric immunobead assay for the detection of BCR-ABL fusion proteins in
      leukemia patients.
AB  - BCR-ABL fusion proteins show increased signaling through their ABL tyrosine
      kinase domain, which can be blocked by specific inhibitors, thereby providing
      effective treatment. This makes detection of BCR-ABL aberrations of utmost
      importance for diagnosis, classification and treatment of leukemia patients. BCR
      ABL aberrations are currently detected by karyotyping, fluorescence in situ
      hybridization (FISH) or PCR techniques, which are time consuming and require
      specialized facilities. We developed a simple flow cytometric immunobead assay
      for detection of BCR-ABL fusion proteins in cell lysates, using a bead-bound anti
      BCR catching antibody and a fluorochrome-conjugated anti-ABL detection antibody.
      We noticed protein stability problems in lysates caused by proteases from mature
      myeloid cells. This problem could largely be solved by adding protease inhibitors
      in several steps of the immunobead assay. Testing of 145 patient samples showed
      fully concordant results between the BCR-ABL immunobead assay and reverse
      transcriptase PCR of fusion gene transcripts. Dilution experiments with BCR-ABL
      positive cell lines revealed sensitivities of at least 1%. We conclude that the
      BCR-ABL immunobead assay detects all types of BCR-ABL proteins in leukemic cells
      with high specificity and sensitivity. The assay does not need specialized
      laboratory facilities other than a flow cytometer, provides results within
      approximately 4 h, and can be run in parallel to routine immunophenotyping.

PMID- 19387468
TI  - Accurate detection of uniparental disomy and microdeletions by SNP array analysis
      in myelodysplastic syndromes with normal cytogenetics.
AB  - Progress in the management of patients with myelodysplastic syndromes (MDS) has
      been hampered by the inability to detect cytogenetic abnormalities in 40-60% of
      cases. We prospectively analyzed matched pairs of bone marrow and buccal cell
      (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP)
      arrays, and identified somatically acquired clonal genomic abnormalities in 21
      patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5
      (15%) had clonal, somatically acquired aberrations by SNP array analysis,
      including 4 with segmental uniparental disomies (UPD) and 1 with three separate
      microdeletions. Each abnormality was detected more readily in CD34+ cells than in
      unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA
      from each patient was necessary to distinguish true clonal genomic abnormalities
      from inherited copy number variations and regions with apparent loss of
      heterozygosity. UPDs affecting chromosome 7q were identified in two patients who
      had a rapidly deteriorating clinical course despite a low-risk International
      Prognostic Scoring System score. Further studies of larger numbers of patients
      will be needed to determine whether 7q UPD detected by SNP array analysis will
      identify higher risk MDS patients at diagnosis, analogous to those with 7q
      cytogenetic abnormalities.

PMID- 19387469
TI  - A rapid urine test for early detection of kidney injury.
AB  - Kidney injury molecule-1 (Kim-1) has been qualified by the Food and Drug
      Administration and European Medicines Agency as a highly sensitive and specific
      urinary biomarker to monitor drug-induced kidney injury in preclinical studies
      and on a case-by-case basis in clinical trials. Here we report the development
      and evaluation of a rapid direct immunochromatographic lateral flow 15-min assay
      for detection of urinary Kim-1 (rat) or KIM-1 (human). The urinary Kim-1 band
      intensity using the rat Kim-1 dipstick significantly correlated with levels of
      Kim-1 as measured by a microbead-based assay, histopathological damage, and
      immunohistochemical assessment of renal Kim-1 in a dose- and time-dependent
      manner. Kim-1 was detected following kidney injury induced in rats by cadmium,
      gentamicin, or bilateral renal ischemia/reperfusion. In humans, the urinary KIM-1
      band intensity was significantly greater in urine from patients with acute kidney
      injury than in urine from healthy volunteers. The KIM-1 dipstick also enabled
      temporal evaluation of kidney injury and recovery in two patients who developed
      postoperative acute kidney injury following cytoreductive surgery for malignant
      mesothelioma with intraoperative local cisplatin administration. We hope that
      future, more extensive studies will confirm the utility of these results, which
      show that the Kim-1/KIM-1 dipsticks can provide a sensitive and accurate
      detection of Kim-1/KIM-1, thereby providing a rapid diagnostic assay for kidney
      damage and facilitating the rapid and early detection of kidney injury in
      preclinical and clinical studies.

PMID- 19387471
TI  - Shining a LAMP on pauci-immune focal segmental glomerulonephritis.
AB  - Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis frequently
      presents with renal involvement manifested by a focal segmental necrotizing
      glomerulonephritis, which is typically pauci-immune. Although considerable
      insight has been gained regarding potential mechanisms of organ damage,
      researchers have remained relatively ignorant of the initiating factors breaking
      immune tolerance. A recent report has provided evidence that molecular mimicry
      may be critical, with immune responsiveness toward a bacterial fimbrial protein
      inducing a cross-reactive autoimmune response toward lysosomal-associated
      membrane protein-2 (LAMP-2). Use of an experimental model demonstrates that this
      response generates ANCA and provokes pulmonary-renal disease, reminiscent of
      human ANCA-associated vasculitis. Greater understanding of the immune mechanisms
      underlying the development of ANCA should lead to more focused approaches to the
      treatment of small-vessel vasculitis.

PMID- 19387470
TI  - AT1a receptor knockout in mice impairs urine concentration by reducing basal
      vasopressin levels and its receptor signaling proteins in the inner medulla.
AB  - Angiotensin II plays an important role in the regulation of blood pressure, body
      salt and fluid balance, and urine concentration. Mice with deletion of the AT(1a)
      receptor develop polyuria and urine concentration defects. We studied the
      mechanisms of these urine concentration defects by treating wild-type and AT(1a)
      knockout mice with arginine vasopressin (AVP) for 2 weeks, controlling their
      water intake, or giving them an osmotic diuretic (sucrose) in order to determine
      whether central or nephrogenic mechanisms were involved. Under basal conditions,
      AT(1a)-knockout mice were hypotensive, had lower plasma AVP, and excreted more
      urine with a markedly reduced osmolality compared with wild-type mice. However,
      basal glomerular filtration rates were similar in both strains of mice. We
      isolated total lysate and membrane proteins from the inner medulla of wild-type
      and mutant mouse kidneys, and found that the amounts of aquaporin 2 (AQP2),
      adenylyl cyclases III and V/VI, and phosphorylated MAP kinases ERK 1/2 proteins
      were all reduced in the inner medulla of the knockout mice. Infusion of AVP
      raised plasma levels and blood pressure proportionally in both strains, but
      polyuria persisted and urine osmolality remained significantly lower in the
      knockout mice. Although AVP increased urine osmolality slightly in water-deprived
      knockout mice, this was well below the basal osmolality of wild-type mice. The
      diuretic response to the hyperosmotic sucrose was also impaired in the knockout
      mice. Neither AVP nor water rationing restored the levels of the inner medullary
      signaling proteins and membrane AQP2 proteins in the knockout mice. We suggest
      that AT(1a) receptor deletion causes polyuria and urine concentration defects by
      decreasing basal AVP release and impairing AVP-induced receptor signaling in the
      inner medulla.

PMID- 19387472
TI  - Genome-wide linkage analysis of serum creatinine in three isolated European
      populations.
AB  - There is increasing evidence for a role of genetic predisposition in the etiology
      of kidney disease, but linkage scans have been poorly replicated. Here we
      performed a genome-wide linkage analysis of serum creatinine on 2859 individuals
      from isolated villages in South Tyrol (Italy), Rucphen (The Netherlands) and Vis
      Island (Croatia), populations that have been stable and permanently resident in
      their region. Linkage of serum creatinine levels to loci on chromosomes 7p14,
      9p21, 11p15, 15q15-21, 16p13, and 18p11 was successfully replicated in at least
      one discovery population or in the pooled analysis. A novel locus was found on
      chromosome 10p11. Linkage to chromosome 22q13, independent of diabetes and
      hypertension, was detected over a region containing the non-muscle myosin heavy
      chain type II isoform A (MYH9) gene (LOD score=3.52). In non-diabetic
      individuals, serum creatinine was associated with this gene in two of the three
      populations and in meta-analysis (SNP rs11089788, P-value=0.0089). In populations
      sharing a homogeneous environment and genetic background, heritability of serum
      creatinine was higher than in outbred populations, with consequent detection of a
      larger number of loci than reported before. Our finding of a replicated
      association of serum creatinine with the MYH9 gene, recently linked to
      pathological renal conditions in African Americans, suggests that this gene may
      also influence kidney function in healthy Europeans.

PMID- 19387473
TI  - A dietary non-human sialic acid may facilitate hemolytic-uremic syndrome.
AB  - Hemolytic-uremic syndrome (HUS) is a systemic disease characterized by
      microvascular endothelial damage, mainly in the gastrointestinal tract and the
      kidneys. A major cause of HUS is Shiga toxigenic Escherichia coli (STEC)
      infection. In addition to Shiga toxin, additional STEC virulence factors may
      contribute to HUS. One is the newly discovered subtilase cytotoxin (SubAB), which
      is highly toxic to eukaryotic cells, and when injected intraperitoneally into
      mice causes pathology resembling that associated with human HUS. Recent data show
      that SubAB exhibits a strong preference for glycans terminating in alpha2-3
      linked N-glycolylneuraminic acid (Neu5Gc), a sialic acid that humans are unable
      to synthesize, because we genetically lack the necessary enzyme. However, Neu5Gc
      can still be found on human cells due to metabolic incorporation from the diet.
      Dietary incorporation happens to be highest in human endothelium and to a lesser
      extent in the intestinal epithelium, the two affected cell types in STEC-induced
      HUS. Mammalian-derived foods such as red meat and dairy products appear to be the
      primary source of dietary Neu5Gc. Ironically, these are also common sources of
      STEC contamination. Taken together, these findings suggest a 'two-hit' process in
      the pathogenesis of human SubAB-induced disease. First, humans eat Neu5Gc-rich
      food, leading to incorporation of Neu5Gc on the surfaces of endothelial and
      intestinal cells. Second, when exposed to a SubAB-producing STEC strain, the
      toxin produced would be able to bind to the intestinal epithelial cells, perhaps
      causing acute gastrointestinal symptoms, and eventually damaging endothelial
      cells in other organs like the kidney, thereby causing HUS.

PMID- 19387474
TI  - Vitamin K deficiency in CKD patients: a modifiable risk factor for vascular
      calcification?
AB  - The purpose of this review is to summarize currently available evidence
      implicating vitamin K in the pathogenesis of vascular calcification (VC), in
      particular arterial medial calcification. In doing so, we try to provide a
      rationale for an interventional clinical study testing whether vitamin K
      supplementation can retard VC or even affect cardiovascular mortality in chronic
      kidney disease patients. Additionally, we wish to give an overview of the current
      literature indicating potential adverse effects of long-term vitamin K
      antagonists in this population.

PMID- 19387475
TI  - Sustained appetite improvement in malnourished dialysis patients by daily ghrelin
      treatment.
AB  - Malnutrition is a common complication in patients on dialysis and is strongly
      associated with poor prognosis. Effective therapy could substantially improve
      morbidity and mortality, but neither enteral nor parenteral supplementation
      provide long-term benefit because of the strong appetite suppression seen in such
      patients. We performed a double-blinded randomized crossover study of a week-long
      treatment with daily subcutaneous ghrelin, a gut hormone that regulates hunger
      through the hypothalamus, in a group of 12 malnourished dialysis patients.
      Ghrelin administration increased ghrelin levels in circulation, modestly reduced
      blood pressure for up to 2 h, and immediately and significantly increased
      appetite, with an increase in energy intake noted at the first study meal.
      Persistence of this effect throughout the week was confirmed with food diaries
      and final study meals. Energy expenditure, measured with free-living pulse and
      motion monitors, was unchanged by ghrelin. Our study shows that daily treatment
      with ghrelin achieves a sustained positive change in energy balance in
      malnourished dialysis patients. Direct manipulation of appetite with ghrelin or
      its analogs represents an attractive and promising therapeutic strategy for this
      difficult clinical problem.

PMID- 19387476
TI  - FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies.
AB  - Fibroblast growth factor receptor (FGFR)2 is regulated on the basis of the
      balance of FGFs, heparan-sulfate proteoglycans, FGFR2 isoforms, endogenous
      inhibitors, and microRNAs. FGFR2 signals cross-talk with hedgehog, bone
      morphogenetic protein, and other regulatory networks. Some cases of congenital
      skeletal disorders with an FGFR2 mutation show skin phenotypes, including acne,
      cutis gyrata, and acanthosis nigricans. Gain-of-function mutations or variations
      of human FGFR2 occur in estrogen receptor-positive breast cancer, diffuse-type
      gastric cancer, and endometrial uterine cancer. Oral administration of AZD2171 or
      Ki23057 inhibits in vivo proliferation of cancer cells with aberrant FGFR2
      activation in rodent therapeutic models. However, loss-of-function mutations of
      FGFR2 are reported in human melanoma. Conditional Fgfr2b knockout in the rodent
      epidermis leads to increased macrophage infiltration to the dermis and adipose
      tissue, epidermal thickening accompanied by basal-layer dysplasia and
      parakeratosis, and the promotion of chemically induced squamous-cell carcinoma.
      Dysregulation of FGFR2 results in a spectrum of bone and skin pathologies and
      several types of cancer.

PMID- 19387478
TI  - From the rarest to the most common: insights from progeroid syndromes into skin
      cancer and aging.
AB  - Despite their rarity, diseases of premature aging, or "progeroid" syndromes, have
      provided important insights into basic mechanisms that may underlie cancer and
      normal aging. In this review, we highlight these recent developments in
      Hutchinson-Gilford progeria syndrome (HGPS), Werner syndrome, Bloom syndrome,
      Cockayne syndrome, trichothiodystrophy, ataxia-telangiectasia, Rothmund-Thomson
      syndrome, and xeroderma pigmentosum. Though they are caused by different
      mutations in various genes and often result in quite disparate phenotypes,
      deciphering the molecular bases of these conditions has served to highlight their
      underlying basic similarities. Studies of progeroid syndromes, particularly HGPS,
      the most dramatic form of premature aging, have contributed to our knowledge of
      fundamental processes of importance to skin biology, including DNA transcription,
      replication, and repair, genome instability, cellular senescence, and stem-cell
      differentiation.

PMID- 19387479
TI  - Antimicrobial and healing efficacy of sustained release nitric oxide
      nanoparticles against Staphylococcus aureus skin infection.
AB  - Staphylococcus aureus (SA) is a leading cause of both superficial and invasive
      infections in community and hospital settings, frequently resulting in chronic
      refractory disease. It is imperative that innovative therapeutics to which the
      bacteria are unlikely to evolve resistance be developed to curtail associated
      morbidity and mortality and ultimately improve our capacity to treat these
      infections. In this study, a previously unreported nitric oxide (NO)-releasing
      nanoparticle technology is applied to the treatment of methicillin-resistant SA
      (MRSA) wound infections. The results show that the nanoparticles exert
      antimicrobial activity against MRSA in a murine wound model. Acceleration of
      infected wound closure in NO-treated groups was clinically shown compared with
      controls. The histology of wounds revealed that NO nanoparticle treatment
      decreased suppurative inflammation, minimal bacterial burden, and less collagen
      degradation, providing potential mechanisms for biological activity. Together,
      these data suggest that these NO-releasing nanoparticles have the potential to
      serve as a novel class of topically applied antimicrobials for the treatment of
      cutaneous infections and wounds.

PMID- 19387480
TI  - Hair follicles are required for optimal growth during lateral skin expansion.
AB  - The hair follicles (HFs) and the interfollicular epidermis (IFE) of intact mature
      skin are maintained by distinct stem cell populations. Upon wounding, however,
      emigration of HF keratinocytes to the IFE plays a role in acute stages of
      healing. In addition to this repair function, rapidly cycling cells of the upper
      HF have been observed transiting to the IFE in neonatal skin. Here we report that
      an absence of HF development leads to shortening and kinking of the mouse tail.
      These skeletal defects are reduced by stimulating keratinocyte proliferation,
      suggesting that they arise from impaired epidermal expansion. We confirm that
      rapidly cycling cells of the HF emigrate to the IFE of the neonatal tail. These
      results suggest that an absence of HFs results in impaired skin growth that is
      unable to keep pace with the rapidly elongating axial skeleton of the tail. Thus,
      in addition to their role in wound repair, HFs can make a significant
      contribution to lateral expansion of the IFE in the absence of trauma.

PMID- 19387477
TI  - Matriptase-deficient mice exhibit ichthyotic skin with a selective shift in skin
      microbiota.
AB  - Suppressor of tumorigenicity 14 (St14) encodes matriptase, a serine protease,
      which regulates processing of profilaggrin to filaggin in vivo. Here, we report
      that transgenic mice with 1% of wild-type St14 levels (St14(hypo/-)) display
      aberrant processing of profilaggrin and model human ichthyotic skin phenotypes.
      Scaling of the skin appears at 1 week of age with underlying epidermal acanthosis
      and orthohyperkeratosis as well as a CD4+ T-cell dermal infiltrate. Upregulation
      of antimicrobial peptides occurs when challenged by exposure to the postnatal
      environment. Direct genomic sequencing of bacterial 16S rRNA genes to query
      microbial diversity identifies a significant shift in both phylogeny and
      community structure between St14(hypo/-) mice and control littermates. St14(hypo/
      ) mice have a selective shift in resident skin microbiota with a decrease of the
      dominant genus of skin bacteria, Pseudomonas and an accompanying increase of
      Corynebacterium and Streptococcus. St14(hypo/-) mice provide early evidence that
      the cutaneous microbiome can be specifically altered by genetic state, which may
      play an important role in modulating skin disease.

PMID- 19387482
TI  - Antimicrobial property of lauric acid against Propionibacterium acnes: its
      therapeutic potential for inflammatory acne vulgaris.
AB  - The strong bactericidal properties of lauric acid (C12:0), a middle chain-free
      fatty acid commonly found in natural products, have been shown in a number of
      studies. However, it has not been demonstrated whether lauric acid can be used
      for acne treatment as a natural antibiotic against Propionibacterium acnes (P.
      acnes), which promotes follicular inflammation (inflammatory acne). This study
      evaluated the antimicrobial property of lauric acid against P. acnes both in
      vitro and in vivo. Incubation of the skin bacteria P. acnes, Staphylococcus
      aureus (S. aureus), and Staphylococcus epidermidis (S. epidermidis) with lauric
      acid yielded minimal inhibitory concentration (MIC) values against the bacterial
      growth over 15 times lower than those of benzoyl peroxide (BPO). The lower MIC
      values of lauric acid indicate stronger antimicrobial properties than that of
      BPO. The detected values of half maximal effective concentration (EC(50)) of
      lauric acid on P. acnes, S. aureus, and S. epidermidis growth indicate that P.
      acnes is the most sensitive to lauric acid among these bacteria. In addition,
      lauric acid did not induce cytotoxicity to human sebocytes. Notably, both
      intradermal injection and epicutaneous application of lauric acid effectively
      decreased the number of P. acnes colonized with mouse ears, thereby relieving P.
      acnes-induced ear swelling and granulomatous inflammation. The obtained data
      highlight the potential of using lauric acid as an alternative treatment for
      antibiotic therapy of acne vulgaris.

PMID- 19387481
TI  - Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor
      stimulators of T-cell proliferation.
AB  - To determine the phenotype and function of myeloid dendritic cells (DCs) from
      human cutaneous squamous-cell carcinoma (SCC), we studied their surface marker
      expression and allo-stimulatory potential ex vivo. There were abundant CD11c(+)
      myeloid DCs, as well as TNF and inducible nitric oxide synthase (iNOS)-producing
      DCs, in and around SCC tumor nests. Although myeloid DCs from SCC, adjacent non
      tumor-bearing skin, and normal skin, were phenotypically similar by flow
      cytometry, and there was a pronounced genomic signature of mature DCs in SCC,
      they showed different T-cell stimulatory potential in an allogeneic mixed
      leukocyte reaction. Myeloid DCs from SCC were less potent stimulators of
      allogeneic T-cell proliferation than DCs from non-tumor-bearing skin. Culture
      with a DC-maturing cytokine cocktail (IL-1beta, IL-6, TNF-alpha, and PGE(2))
      enhanced stimulatory potential in DCs from non-tumor-bearing skin, whereas SCC
      associated DCs remained poor stimulators of T-cell proliferation. The
      microenvironment associated with SCC showed expression of TGF-beta, IL-10, and
      VEGF-A, factors capable of suppressing the DC function. These findings indicate
      that CD11c(+)/HLA-DR(hi) DCs from SCC are mature, but are not potent stimulators
      of T-cell proliferation compared with phenotypically similar DCs isolated from
      non-tumor-bearing skin. Identification of mechanisms responsible for suppression
      of tumor-associated DCs may provide insight into the evasion of
      immunosurveillance by SCC.

PMID- 19387483
TI  - QuickMap: a public tool for large-scale gene therapy vector insertion site
      mapping and analysis.
AB  - Several events of insertional mutagenesis in pre-clinical and clinical gene
      therapy studies have created intense interest in assessing the genomic insertion
      profiles of gene therapy vectors. For the construction of such profiles, vector
      flanking sequences detected by inverse PCR, linear amplification-mediated-PCR or
      ligation-mediated-PCR need to be mapped to the host cell's genome and compared to
      a reference set. Although remarkable progress has been achieved in mapping gene
      therapy vector insertion sites, public reference sets are lacking, as are the
      possibilities to quickly detect non-random patterns in experimental data. We
      developed a tool termed QuickMap, which uniformly maps and analyzes human and
      murine vector-flanking sequences within seconds (available at www.gtsg.org).
      Besides information about hits in chromosomes and fragile sites, QuickMap
      automatically determines insertion frequencies in +/- 250 kb adjacency to genes,
      cancer genes, pseudogenes, transcription factor and (post-transcriptional) miRNA
      binding sites, CpG islands and repetitive elements (short interspersed nuclear
      elements (SINE), long interspersed nuclear elements (LINE), Type II elements and
      LTR elements). Additionally, all experimental frequencies are compared with the
      data obtained from a reference set, containing 1 000 000 random integrations
      ('random set'). Thus, for the first time a tool allowing high-throughput
      profiling of gene therapy vector insertion sites is available. It provides a
      basis for large-scale insertion site analyses, which is now urgently needed to
      discover novel gene therapy vectors with 'safe' insertion profiles.

PMID- 19387484
TI  - Efficient lentiviral gene transfer into corneal stroma cells using a femtosecond
      laser.
AB  - We investigated a new procedure for gene transfer into the stroma of pig cornea
      for the delivery of therapeutic factors. A delimited space was created at 110 mum
      depth with a LDV femtosecond laser in pig corneas, and a HIV1-derived lentiviral
      vector expressing green fluorescent protein (GFP) (LV-CMV-GFP) was injected into
      the pocket. Corneas were subsequently dissected and kept in culture as explants.
      After 5 days, histological analysis of the explants revealed that the corneal
      pockets had closed and that the gene transfer procedure was efficient over the
      whole pocket area. Almost all the keratocytes were transduced in this area.
      Vector diffusion at right angles to the pocket's plane encompasses four
      (endothelium side) to 10 (epithelium side) layers of keratocytes. After 21 days,
      the level of transduction was similar to the results obtained after 5 days. The
      femtosecond laser technique allows a reliable injection and diffusion of
      lentiviral vectors to efficiently transduce stromal cells in a delimited area.
      Showing the efficacy of this procedure in vivo could represent an important step
      toward treatment or prevention of recurrent angiogenesis of the corneal stroma.

PMID- 19387485
TI  - Reduction of nitrate in Shewanella oneidensis depends on atypical NAP and NRF
      systems with NapB as a preferred electron transport protein from CymA to NapA.
AB  - In the genome of Shewanella oneidensis, a napDAGHB gene cluster encoding
      periplasmic nitrate reductase (NapA) and accessory proteins and an nrfA gene
      encoding periplasmic nitrite reductase (NrfA) have been identified. These two
      systems seem to be atypical because the genome lacks genes encoding cytoplasmic
      membrane electron transport proteins, NapC for NAP and NrfBCD/NrfH for NRF,
      respectively. Here, we present evidence that reduction of nitrate to ammonium in
      S. oneidensis is carried out by these atypical systems in a two-step manner.
      Transcriptional and mutational analyses suggest that CymA, a cytoplasmic membrane
      electron transport protein, is likely to be the functional replacement of both
      NapC and NrfH in S. oneidensis. Surprisingly, a strain devoid of napB encoding
      the small subunit of nitrate reductase exhibited the maximum cell density sooner
      than the wild type. Further characterization of this strain showed that nitrite
      was not detected as a free intermediate in its culture and NapB provides a
      fitness gain for S. oneidensis to compete for nitrate in the environments. On the
      basis results from mutational analyses of napA, napB, nrfA and napBnrfA in-frame
      deletion mutants, we propose that NapB is able to favor nitrate reduction by
      routing electrons to NapA exclusively.

PMID- 19387486
TI  - Rumen-like methanogens identified from the crop of the folivorous South American
      bird, the hoatzin (Opisthocomus hoazin).
AB  - The hoatzin is the only known avian species with foregut fermentation. It is a
      primarily folivorous feeder and has a distended crop and lower/distal esophagus,
      which has evolved for the microbial fermentation of ingested feed. Crop samples
      collected from 10 individual animals from the Apure River area, Apure State,
      Venezuela were examined for the presence and density of methanogens using 16S
      rRNA gene clone libraries and real-time PCR prepared from pooled and individual
      PCR products. A total of 197 clones were examined, revealing 24 different
      methanogen 16S rRNA sequences, or phylotypes. Of the 24 unique phylotypes, 16
      (171 of 197 clones) formed five unique clades within the genus Methanobrevibacter
      with the largest group of clones (118 clones) 98.7% similar to Methanobrevibacter
      ruminantium. The remaining eight phylotypes (26 clones) formed four unique clades
      that had only 94.0-96.7% identity to Methanosphaera stadtmanae. Based upon 98%
      sequence identity, we identified 17 of the 24 methanogen phylotypes from the
      hoatzin as possible new species and strains, with three phylotypes representing
      possible new genera (<94.5% sequence identity). Although none of the hoatzin
      methanogen phylotypes had 100% sequence identity to any other archaeal sequences
      in the GenBank database, the hoatzin crop methanogen sequences formed sister
      groups with known rumen methanogens. Mean population densities (numbers per gram
      wet weight) of methanogenic archaea, rumen bacteria and ciliate protozoa,
      estimated using real-time PCR, were 5.80 x 10(9), 7.93 x 10(12) and 3.31 x 10(5),
      respectively. The crop microbial data presented here provide an excellent example
      of convergent evolution of foregut fermentation in the hoatzin, similar to that
      of ruminants.

PMID- 19387487
TI  - Bacteria, not archaea, restore nitrification in a zinc-contaminated soil.
AB  - Biological ammonia oxidation had long been thought to be mediated solely by
      discrete clades of beta- and gamma-proteobacteria (ammonia-oxidizing bacteria;
      AOB). However, ammonia-oxidizing Crenarchaeota (ammonia-oxidizing archaea; AOA)
      have recently been identified and proposed to be the dominant agents of ammonia
      oxidation in soils. Nevertheless, the dynamics of AOB versus AOA, and their
      relative contribution to soil ammonia oxidation and ecosystem functioning on
      stress and environmental perturbation, remain unknown. Using a 3-year
      longitudinal field study and the amoA gene as a molecular marker, we demonstrate
      that AOB, but not AOA, mediate recovery of nitrification after zinc (Zn)
      contamination. Pristine soils showed approximately equal amoA gene copy numbers
      and transcript levels for AOB and AOA. At an intermediate Zn dose (33.7 mmol Zn
      per kg), ammonia oxidation was completely inhibited, and the numbers of AOB and
      AOA amoA gene copies and gene transcripts were reduced. After 2 years, ammonia
      oxidation in the field soils was fully restored to preexposure levels, and this
      restoration of function was concomitant with an increase of AOB amoA gene copy
      and gene transcript numbers. Analysis of the restored community revealed
      domination by a phylogenetically distinct Zn-tolerant Nitrosospira sp. community.
      In contrast, the numbers of AOA amoA gene copies and gene transcripts remained 3-
      and 10(4)-fold lower than recovered AOB values, respectively. Thus, although
      recent findings have emphasized a dominant role of archaea in soil-borne ammonia
      oxidation, we demonstrate that a phylogenetic shift within the AOB community
      drives recovery of nitrification from Zn contamination in this soil.

PMID- 19387488
TI  - S5a promotes protein degradation by blocking synthesis of nondegradable forked
      ubiquitin chains.
AB  - Ubiquitin (Ub)-protein conjugates formed by purified ring-finger or U-box E3s
      with the E2, UbcH5, resist degradation and disassembly by 26S proteasomes. These
      chains contain multiple types of Ub forks in which two Ub's are linked to
      adjacent lysines on the proximal Ub. We tested whether cells contain factors that
      prevent formation of nondegradable conjugates and whether the forked chains
      prevent proteasomal degradation. S5a is a ubiquitin interacting motif (UIM)
      protein present in the cytosol and in the 26S proteasome. Addition of S5a or a
      GST-fusion of S5a's UIM domains to a ubiquitination reaction containing 26S
      proteasomes, UbcH5, an E3 (MuRF1 or CHIP), and a protein substrate, dramatically
      stimulated its degradation, provided S5a was present during ubiquitination. Mass
      spectrometry showed that S5a and GST-UIM prevented the formation of Ub forks
      without affecting synthesis of standard isopeptide linkages. The forked Ub chains
      bind poorly to 26S proteasomes unlike those synthesized with S5a present or
      linked to Lys63 or Lys48 chains. Thus, S5a (and presumably certain other UIM
      proteins) function with certain E3/E2 pairs to ensure synthesis of efficiently
      degraded non-forked Ub conjugates.

PMID- 19387489
TI  - Comparative profiling identifies C13orf3 as a component of the Ska complex
      required for mammalian cell division.
AB  - Proliferation of mammalian cells requires the coordinated function of many
      proteins to accurately divide a cell into two daughter cells. Several RNAi
      screens have identified previously uncharacterised genes that are implicated in
      mammalian cell division. The molecular function for these genes needs to be
      investigated to place them into pathways. Phenotypic profiling is a useful method
      to assign putative functions to uncharacterised genes. Here, we show that the
      analysis of protein localisation is useful to refine a phenotypic profile. We
      show the utility of this approach by defining a function of the previously
      uncharacterised gene C13orf3 during cell division. C13orf3 localises to
      centrosomes, the mitotic spindle, kinetochores, spindle midzone, and the cleavage
      furrow during cell division and is specifically phosphorylated during mitosis.
      Furthermore, C13orf3 is required for centrosome integrity and anaphase onset.
      Depletion by RNAi leads to mitotic arrest in metaphase with an activation of the
      spindle assembly checkpoint and loss of sister chromatid cohesion. Proteomic
      analyses identify C13orf3 (Ska3) as a new component of the Ska complex and show a
      direct interaction with a regulatory subunit of the protein phosphatase PP2A. All
      together, these data identify C13orf3 as an important factor for metaphase to
      anaphase progression and highlight the potential of combined RNAi screening and
      protein localisation analyses.

PMID- 19387490
TI  - Acetylation of cyclin T1 regulates the equilibrium between active and inactive P
      TEFb in cells.
AB  - The elongation competence of the RNA polymerase II complex is critically
      dependent on the positive transcription elongation factor b (P-TEFb). P-TEFb
      exists in two forms in cells, an active form composed of cyclin T1 and CDK9 and
      an inactive form, in which cyclin T1/CDK9 is sequestered by Hexim1 and 7SK snRNA.
      Here, we report that partitioning of active and inactive P-TEFb is regulated by
      acetylation of cyclin T1. Cyclin T1 acetylation triggers dissociation of Hexim1
      and 7SK snRNA from cyclin T1/CDK9 and activates the transcriptional activity of P
      TEFb. This activation is lost in P-TEFb complexes containing cyclin T1 that can
      no longer be acetylated. An acetylation-deficient cyclin T1 mutant dominantly
      suppresses NF-kappaB-mediated activation of the interleukin-8 promoter but
      continues to synergize normally with the HIV Tat protein to transactivate the HIV
      long terminal repeat. These findings support the model that acetylation of cyclin
      T1 serves as a physiological switch that liberates P-TEFb from its endogenous
      inhibitors Hexim1 and 7SK snRNA, but is not required for the cooperative action
      with HIV Tat.

PMID- 19387491
TI  - Auto-phosphorylation of a voltage-gated K+ channel controls non-associative
      learning.
AB  - Here, we characterize a new K(+) channel-kinase complex that operates in the
      metazoan Caenorhabditis elegans to control learning behaviour. This channel is
      composed of a pore-forming subunit, dubbed KHT-1 (73% homology to human Kv3.1),
      and the accessory subunit MPS-1, which shows kinase activity. Genetic,
      biochemical and electrophysiological evidence show that KHT-1 and MPS-1 form a
      complex in vitro and in native mechanosensory PLM neurons, and that KHT-1 is a
      substrate for the kinase activity of MPS-1. Behavioural analysis further shows
      that the kinase activity of MPS-1 is specifically required for habituation to
      repetitive mechanical stimulation. Thus, worms bearing an inactive MPS-1 variant
      (D178N) respond normally to touch on the body but do not habituate to repetitive
      mechanical stimulation such as tapping on the side of the Petri dish. Hence, the
      phosphorylation status of KHT-1-MPS-1 seems to be linked to distinct behavioural
      responses. In the non-phosphorylated state the channel is necessary for the
      normal function of the touch neurons. In the auto-phosphorylated state the
      channel acts to induce neuronal adaptation to mechanical stimulation. Taken
      together, these data establish a new mechanism of dynamic regulation of
      electrical signalling in the nervous system.

PMID- 19387492
TI  - Yeast Uri1p promotes translation initiation and may provide a link to
      cotranslational quality control.
AB  - Translation initiation in eukaryotes is accomplished by a large set of
      translation initiation factors, some of which are regulated by signals monitoring
      intracellular and environmental conditions. Here, we show that Uri1p is required
      for efficient translation initiation in budding yeast. Indeed, uri1Delta cells
      are slow growing, sensitive to translation inhibitors and they exhibit an
      increased 80S peak in polysome profiles. Moreover, GCN4 translation is
      derepressed in uri1Delta cells, strongly supporting an initiation defect. Genetic
      and biochemical experiments indicate that Uri1p interacts with the translation
      initiation factor eIF1A and promotes ternary complex (TC) recruitment to the 40S
      subunit. Interestingly, we found that Uri1p is also part of a chaperone-network,
      including the prefoldin Pfd6p and several other proteins involved in
      cotranslational quality control such as the ribosome-associated Hsp70 chaperone
      Ssb1p, the Hsp40 Sis1p and the translation elongation factor eEF1A. Together with
      genetic data, these interactions indicate that Uri1p may coordinate translation
      initiation and cotranslational quality control.

PMID- 19387493
TI  - Lte1, Cdc14 and MEN-controlled Cdk inactivation in yeast coordinate rDNA
      decompaction with late telophase progression.
AB  - The mechanism of chromatin compaction in mitosis has been well studied, while
      little is known about what controls chromatin decompaction in early G1 phase. We
      have localized the Condensin subunit Brn1 to a compact spiral of rDNA in mitotic
      budding yeast cells. Brn1 release and the resulting rDNA decompaction in late
      telophase coincided with mitotic spindle dissociation, and occurred
      asymmetrically (daughter cells first). We immunoprecipitated the GTP-exchange
      factor Lte1, which helps activate the mitotic exit network (MEN) in anaphase,
      with mitotic Brn1. In lteDelta cells Brn1 release was delayed, even at
      temperatures that do not impair mitotic exit. Mutations in MEN pathway components
      that act downstream of Lte1 similarly delayed rDNA decompaction. We found that
      Brn1 release in wild-type cells coincided with the release of Cdc14 phosphatase
      from the nucleolus and with mitotic CDK inactivation, yet it could be selectively
      delayed by perturbation of the MEN pathway. This may argue that different levels
      of Cdk inactivation control spindle disassembly and chromatin decompaction.
      Mutation of lte1 also impaired rotation of the nucleus in early G1.

PMID- 19387495
TI  - Inter-subunit interaction of gastric H+,K+-ATPase prevents reverse reaction of
      the transport cycle.
AB  - The gastric H(+),K(+)-ATPase is an ATP-driven proton pump responsible for
      generating a million-fold proton gradient across the gastric membrane. We present
      the structure of gastric H(+),K(+)-ATPase at 6.5 A resolution as determined by
      electron crystallography of two-dimensional crystals. The structure shows the
      catalytic alpha-subunit and the non-catalytic beta-subunit in a pseudo-E(2)P
      conformation. Different from Na(+),K(+)-ATPase, the N-terminal tail of the beta
      subunit is in direct contact with the phosphorylation domain of the alpha
      subunit. This interaction may hold the phosphorylation domain in place, thus
      stabilizing the enzyme conformation and preventing the reverse reaction of the
      transport cycle. Indeed, truncation of the beta-subunit N-terminus allowed the
      reverse reaction to occur. These results suggest that the beta-subunit N-terminus
      prevents the reverse reaction from E(2)P to E(1)P, which is likely to be relevant
      for the generation of a large H(+) gradient in vivo situation.

PMID- 19387494
TI  - The antiapoptotic protein AAC-11 interacts with and regulates Acinus-mediated DNA
      fragmentation.
AB  - The nuclear factor Acinus has been suggested to mediate apoptotic chromatin
      condensation after caspase cleavage. However, this role has been challenged by
      recent observations suggesting a contribution of Acinus in apoptotic
      internucleosomal DNA cleavage. We report here that AAC-11, a survival protein
      whose expression prevents apoptosis that occurs on deprivation of growth factors,
      physiologically binds to Acinus and prevents Acinus-mediated DNA fragmentation.
      AAC-11 was able to protect Acinus from caspase-3 cleavage in vivo and in vitro,
      thus interfering with its biological function. Interestingly, AAC-11 depletion
      markedly increased cellular sensitivity to anticancer drugs, whereas its
      expression interfered with drug-induced cell death. AAC-11 possesses a leucine
      zipper domain that dictates, upon oligomerization, its interaction with Acinus as
      well as the antiapoptotic effect of AAC-11 on drug-induced cell death. A cell
      permeable peptide that mimics the leucine-zipper subdomain of AAC-11, thus
      preventing its oligomerization, inhibited the AAC-11-Acinus complex formation and
      potentiated drug-mediated apoptosis in cancer cells. Our results, therefore, show
      that targeting AAC-11 might be a potent strategy for cancer treatment by
      sensitization of tumour cells to chemotherapeutic drugs.

PMID- 19387496
TI  - Isolation, biology and chemistry of the disorazoles: new anti-cancer
      macrodiolides.
AB  - Covering: 1994 to 2008. The disorazoles comprise a family of 29 closely related
      macrocyclic polyketides isolated in 1994 from the fermentation broth of the
      gliding myxobacterium Sorangium cellulosum. Disorazoles A1, E and C1 have shown
      exceptional biological activites toward inhibiting the proliferation of human
      cancer cell lines in picomolar and nanomolar concentrations through the
      disruption of microtubule polymerization. This review gives a brief introduction
      describing the biosynthesis and the significance of the disorazoles as a new
      class of microtubulin disruptors. Another portion of the review focuses on the
      biology of the disorazoles, specifically disorazole A1 and C1, and their
      antiproliferative efficacy against animal and human tumor cell lines, as well as
      the available SAR data. The majority of the discussion addresses synthetic
      efforts, including partial syntheses of various disorazoles and a summary of the
      total synthesis of disorazole C1.

PMID- 19387497
TI  - Recent advances in the chemistry, biosynthesis and pharmacology of rapamycin
      analogs.
AB  - Covering: 2003 to 2008. In the period 1998 to 2003, a number of reviews have
      appeared evaluating the potential of rapamycin and other immunophilin ligands as
      therapies for cancer, organ transplantation, restenosis prevention, autoimmune
      disorders, and neurodegenerative diseases. This review aims to evaluate advances
      in the field since that time, specifically detailing progress in: (i) the role of
      rapamycin in inhibiting its principal cellular target, the mammalian target of
      rapamycin (mTOR) in both of its protein complexes, (ii) understanding the role of
      specific genes in the mechanism of rapamycin biosynthesis, (iii) the production
      of novel analogs of rapamycin via precursor-directed biosynthesis, (iv) the
      enzymology of the pipecolate incorporating enzyme (RapL) in vitro, and (v) the
      pharmacology and mechanistic chemical biology of rapamycin analog mediated
      neuroprotection and neuroregeneration.

PMID- 19387498
TI  - Design of biologically active heparan sulfate and heparin using an enzyme-based
      approach.
AB  - Covering: up to August 2008. Heparan sulfate (HS) is a highly sulfated
      polysaccharide that plays essential physiological and pathophysiological roles.
      Heparin, a special form of HS, is a commonly used anticoagulant drug. The
      biosynthesis of HS involves numerous enzymes, including sulfotransferases,
      glycosyl transferases and an epimerase. It is widely believed that unique
      sulfation patterns is critical for elucidating the function-structure
      relationship of this important class of biomolecules. The chemical syntheses of
      such sulfated saccharides, especially molecules larger than an octasaccharide,
      are extremely difficult. Therefore, employing HS biosynthetic enzymes to
      synthesize HS that has the desired biological functions offers an attractive
      alternative. This review presents the recent progress on this approach. In
      addition, we discuss the mechanism used by HS sulfotransferases to recognize
      specific sulfated saccharide sequences. 186 References are cited.

PMID- 19387499
TI  - Antitumor compounds from actinomycetes: from gene clusters to new derivatives by
      combinatorial biosynthesis.
AB  - Covering: up to October 2008. Antitumor compounds produced by actinomycetes and
      novel derivatives generated by combinatorial biosynthesis are reviewed (with 318
      references cited.) The different structural groups for which the relevant gene
      clusters have been isolated and characterized are reviewed, with a description of
      the strategies used for the generation of the novel derivatives and the
      activities of these compounds against tumor cell lines.

PMID- 19387500
TI  - Synthetic efforts toward cyathane diterpenoid natural products.
AB  - Covering: 2000 to 2008. Previous review: D. L. Wright and C. R. Whitehead, Org.
      Prep. Proced. Int., 2000, 32, 309-330. An overview of synthetic efforts toward
      cyathane diterpenoid natural products from the year 2000 to present is provided.
      The emphasis of this review is the various ring-constructing and stereoforming
      strategies employed in these synthetic routes.

PMID- 19387501
TI  - Diterpenes from gorgonian corals.
AB  - Covering: 1995 to April 2008. Gorgonian corals continue to provide a wealth of
      novel structures, many of which exhibit potentially useful biological activity.
      Notably, the families Briareidae, Gorgoniidae and Plexauridae have been
      demonstrated to contain a wide variety of natural products including steroids,
      acetogenins, sesquiterpenes and diterpenes. The most common of the gorgonian
      natural products are the diterpenes, and the intent of this review is to describe
      such compounds isolated from gorgonian corals, with a focus on the structures of
      new compounds as well as their biological activity. There have been developments
      improving our understanding of the biosynthetic origin of selected diterpenes,
      and these will also be discussed. This review describes 602 new compounds from
      177 articles.

PMID- 19387502
TI  - Rule-based clustering for gene promoter structure discovery.
AB  - BACKGROUND: The genetic cellular response to internal and external changes is
      determined by the sequence and structure of gene-regulatory promoter regions.
      OBJECTIVES: Using data on gene-regulatory elements (i.e., either putative or
      known transcription factor binding sites) and data on gene expression profiles we
      can discover structural elements in promoter regions and infer the underlying
      programs of gene regulation. Such hypotheses obtained in silico can greatly
      assist us in experiment planning. The principal obstacle for such approaches is
      the combinatorial explosion in different combinations of promoter elements to be
      examined. METHODS: Stemming from several state-of-the-art machine learning
      approaches we here propose a heuristic, rule-based clustering method that uses
      gene expression similarity to guide the search for informative structures in
      promoters, thus exploring only the most promising parts of the vast and
      expressively rich rule-space. RESULTS: We present the utility of the method in
      the analysis of gene expression data on budding yeast S. cerevisiae where cells
      were induced to proliferate peroxisomes. CONCLUSIONS: We demonstrate that the
      proposed approach is able to infer informative relations uncovering relatively
      complex structures in gene promoter regions that regulate gene expression.

PMID- 19387503
TI  - Learning susceptibility of a pathogen to antibiotics using data from similar
      pathogens.
AB  - OBJECTIVES: Selection of empirical antibiotic therapy relies on knowledge of the
      in vitro susceptibilities of potential pathogens to antibiotics. In this paper
      the limitations of this knowledge are outlined and a method that can reduce some
      of the problems is developed. METHODS: We propose hierarchical Dirichlet learning
      for estimation of pathogen susceptibilities to antibiotics, using data from a
      group of similar pathogens in a bacteremia database. RESULTS: A threefold cross
      validation showed that maximum likelihood (ML) estimates of susceptibilities
      based on individual pathogens gave a distance between estimates obtained from the
      training set and observed frequencies in the validation set of 16.3%. Estimates
      based on the initial grouping of pathogens gave a distance of 16.7%. Dirichlet
      learning gave a distance of 15.6%. Inspection of the pathogen groups led to
      subdivision of three groups, Citrobacter, Other Gram Negatives and Acinetobacter,
      out of 26 groups. Estimates based on the subdivided groups gave a distance of
      15.4% and Dirichlet learning further reduced this to 15.0%. The optimal size of
      the imaginary sample inherited from the group was 3. CONCLUSION: Dirichlet
      learning improved estimates of susceptibilities relative to ML estimators based
      on individual pathogens and to classical grouped estimators. The initial pathogen
      grouping was well founded and improvement by subdivision of the groups was only
      obtained in three groups. Dirichlet learning was robust to these revisions of the
      grouping, giving improved estimates in both cases, while the group-based
      estimates only gave improved estimates after the revision of the groups.

PMID- 19387504
TI  - Intelligent interactive visual exploration of temporal associations among
      multiple time-oriented patient records.
AB  - OBJECTIVES: To design, implement and evaluate the functionality and usability of
      a methodology and a tool for interactive exploration of time and value
      associations among multiple-patient longitudinal data and among meaningful
      concepts derivable from these data. METHODS: We developed a new, user-driven,
      interactive knowledge-based visualization technique, called Temporal Association
      Charts (TACs). TACs support the investigation of temporal and statistical
      associations within multiple patient records among both concepts and the temporal
      abstractions derived from them. The TAC methodology was implemented as part of an
      interactive system, called VISITORS, which supports intelligent visualization and
      exploration of longitudinal patient data. The TAC module was evaluated for
      functionality and usability by a group of ten users, five clinicians and five
      medical informaticians. Users were asked to answer ten questions using the
      VISITORS system, five of which required the use of TACs. RESULTS: Both types of
      users were able to answer the questions in reasonably short periods of time (a
      mean of 2.5 +/- 0.27 minutes) and with high accuracy (95.3 +/- 4.5 on a 0-100
      scale), without a significant difference between the two groups. All five
      questions requiring the use of TACs were answered with similar response times and
      accuracy levels. Similar accuracy scores were achieved for questions requiring
      the use of TACs and for questions requiring the use only of general exploration
      operators. However, response times when using TACs were slightly longer.
      CONCLUSIONS: TACs are functional and usable. Their use results in a uniform
      performance level, regardless of the type of clinical question or user group
      involved.

PMID- 19387505
TI  - A framework for representation and visualization of 3D shape variability of
      organs in an interactive anatomical atlas.
AB  - OBJECTIVES: Computerized anatomical 3D atlases allow interactive exploration of
      the human anatomy and make it easy for the user to comprehend complex 3D
      structures and spatial interrelationships among organs. Besides the anatomy of
      one reference body inter-individual shape variations of organs in a population
      are of interest as well. In this paper, a new framework for representation and
      visualization of 3D shape variability of anatomical objects within an interactive
      3D atlas is presented. METHODS: In the VOXEL-MAN atlases realistic 3D
      visualizations of organs in high quality are generated for educational purposes
      using volume-based object representations. We extended the volume-based
      representation of organs to enable the 3D visualization of organs' shape
      variability in the atlas. Therefore, the volume-based representation of the inner
      organs in the atlas is combined with a medial representation of organs of a
      population creating a compact description of shape variability. RESULTS: With the
      framework developed different shape variations of an organ can be visualized
      within the context of a volume-based anatomical model. Using shape models of the
      kidney and the breathing lung as examples we demonstrate new possibilities such
      an approach offers for medical education. Furthermore, attributes like gender,
      age or pathology as well as shape attributes are assigned to each shape variant
      which can be used for selecting specific organs of the population. CONCLUSIONS:
      The inclusion of anatomical variability in a 3D interactive atlas presents
      considerable challenges, since such a system offers the chance to explore how
      anatomical structures vary in large populations, across age, gender and races,
      and in different disease states. The framework presented is a basis for the
      development of specialized variability atlases that focus e.g. on specific
      regions of the human body, groups of organs or specific topics of interest.

PMID- 19387506
TI  - How do cancer registries in europe estimate completeness of registration?
AB  - OBJECTIVES: Several methods for estimating completeness in cancer registries have
      been proposed. Little is known about their relative merits. Before embarking on a
      systematic comparison of methods we wanted to know which indicators were
      currently in use and whether there had been comparative investigations of
      estimation methods. METHODS: We performed a survey among European cancer
      registries asking which methods for estimating completeness they used and whether
      they had performed comparisons of methods. RESULTS: One hundred and ninety-five
      European cancer registries were contacted after identification using membership
      directories of the European Network of Cancer Registries (ENCR) and of the
      International Association of Cancer Registries (IACR). Fifty-six (29%; 22%-36%)
      of the 195 cancer registries replied. Forty-eight (86%; 74%-94%) of these stated
      that they estimated completeness. Thirty-five (73%; 58%-85%) used historic
      comparisons, 31 (65%; 49%-78%) compared their data with a reference registry, 28
      (58%; 43%-72%) registries used mortality incidence ratio. Capture-recapture
      methods were applied in only 12 (25%; 14%-40%) registries. The flow method was
      used by ten (21%; 10%-35%) registries. There were regional differences in the use
      of methods. Comparisons of methods were rare and usually restricted to real data
      at hand. A systematic comparison including all indicators actually in use in
      cancer registries was not reported. CONCLUSIONS: A comparison of methods under
      well defined realistic conditions seems to be indicated. Unifying the methods for
      estimating completeness would improve validity of comparisons between cancer
      registries.

PMID- 19387507
TI  - Prediction of postpartum depression using multilayer perceptrons and pruning.
AB  - OBJECTIVE: The main goal of this paper is to obtain a classification model based
      on feed-forward multilayer perceptrons in order to improve postpartum depression
      prediction during the 32 weeks after childbirth with a high sensitivity and
      specificity and to develop a tool to be integrated in a decision support system
      for clinicians. MATERIALS AND METHODS: Multilayer perceptrons were trained on
      data from 1397 women who had just given birth, from seven Spanish general
      hospitals, including clinical, environmental and genetic variables. A prospective
      cohort study was made just after delivery, at 8 weeks and at 32 weeks after
      delivery. The models were evaluated with the geometric mean of accuracies using a
      hold-out strategy. RESULTS: Multilayer perceptrons showed good performance (high
      sensitivity and specificity) as predictive models for postpartum depression.
      CONCLUSIONS: The use of these models in a decision support system can be
      clinically evaluated in future work. The analysis of the models by pruning leads
      to a qualitative interpretation of the influence of each variable in the interest
      of clinical protocols.

PMID- 19387508
TI  - Efficiency of CYP2C9 genetic test representation for automated pharmacogenetic
      decision support.
AB  - OBJECTIVES: We investigated the suitability of representing discrete genetic test
      results in the electronic health record (EHR) as individual single nucleotide
      polymorphisms (SNPs) and as alleles, using the CYP2C9 gene and its polymorphic
      states, as part of a pilot study. The purpose of our investigation was to
      determine the appropriate level of data abstraction when reporting genetic test
      results in the EHR that would allow meaningful interpretation and clinical
      decision support based on current knowledge, while retaining sufficient
      information in order to enable reinterpretation of the results in the context of
      future discoveries. METHODS: Based on the SNP & allele models, we designed two
      separate lab panels within the laboratory information system, one containing SNPs
      and the other containing alleles, built separate rules in the clinical decision
      support system based on each model, and evaluated the performance of these rules
      in an EHR simulation environment using real-world scenarios. RESULTS: Although
      decision-support rules based on allele model required significantly less
      computational time than rules based on SNP model, no difference was observed on
      the total time taken to chart medication orders between rules based on these two
      models. CONCLUSIONS: Both, SNP- and allele-based models, can be used effectively
      for representing genetic test results in the EHR without impacting clinical
      decision support systems. While storing and reporting genetic test results as
      alleles allow for the construction of simpler decision-support rules, and make it
      easier to present these results to clinicians, SNP-based model can retain a
      greater amount of information that could be useful for future reinterpretation.

PMID- 19387509
TI  - On Graphically Checking Goodness-of-fit of Binary Logistic Regression Models.
AB  - OBJECTIVES: This paper is concerned with checking goodness-of-fit of binary
      logistic regression models. For the practitioners of data analysis, the broad
      classes of procedures for checking goodness-of-fit available in the literature
      are described. The challenges of model checking in the context of binary logistic
      regression are reviewed. As a viable solution, a simple graphical procedure for
      checking goodness-of-fit is proposed. METHODS: The graphical procedure proposed
      relies on pieces of information available from any logistic analysis; the focus
      is on combining and presenting these in an informative way. RESULTS: The
      information gained using this approach is presented with three examples. In the
      discussion, the proposed method is put into context and compared with other
      graphical procedures for checking goodness-of-fit of binary logistic models
      available in the literature. CONCLUSION: A simple graphical method can
      significantly improve the understanding of any logistic regression analysis and
      help to prevent faulty conclusions.

PMID- 19387510
TI  - Estimation of patient accrual rates in clinical trials based on routine data from
      hospital information systems.
AB  - BACKGROUND: Delayed patient recruitment is a common problem in clinical trials.
      According to the literature, only about a third of medical research studies
      recruit their planned number of patients within the time originally specified.
      OBJECTIVES: To provide a method to estimate patient accrual rates in clinical
      trials based on routine data from hospital information systems (HIS). METHODS:
      Based on inclusion and exclusion criteria for each trial, a specific HIS report
      is generated to list potential trial subjects. Because not all information
      relevant for assessment of patient eligibility is available as coded HIS items, a
      sample of this patient list is reviewed manually by study physicians. Proportions
      of matching and non-matching patients are analyzed with a Chi-squared test. An
      estimation formula for patient accrual rate is derived from this data. RESULTS:
      The method is demonstrated with two datasets from cardiology and oncology. HIS
      reports should account for previous disease episodes and eliminate duplicate
      persons. CONCLUSION: HIS data in combination with manual chart review can be
      applied to estimate patient recruitment for clinical trials.

PMID- 19387511
TI  - A Simple Modeling-free Method Provides Accurate Estimates of Sensitivity and
      Specificity of Longitudinal Disease Biomarkers.
AB  - OBJECTIVE: To assess the time-dependent accuracy of a continuous longitudinal
      biomarker used as a test for early diagnosis or prognosis. METHODS: A method for
      accuracy assessment is proposed taking into account the marker measurement time
      and the delay between marker measurement and outcome. It dealt with markers
      having interval-censored measurements and a detection threshold. The threshold
      crossing times were assessed by a Bayesian method. A numerical study was
      conducted to test the procedures that were later applied to PCR measurements for
      prediction of cytomegalovirus disease after renal transplantation. RESULTS: The
      Bayesian method corrected the bias induced by interval-censored measurements on
      sensitivity estimates, with corrections from 0.07 to 0.3. In the application to
      cytomegalovirus disease, the Bayesian method estimated the area under the ROC
      curve to be over 75% during the first 20 days after graft and within five days
      between marker measurement and disease onset. However, the accuracy decreased
      quickly as that delay increased and late after graft. CONCLUSIONS: The proposed
      Bayesian method is easy to implement for assessing the time-dependent accuracy of
      a longitudinal biomarker and gives unbiased results under some conditions.

PMID- 19387512
TI  - Estimation of distribution algorithms as logistic regression regularizers of
      microarray classifiers.
AB  - OBJECTIVES: The "large k (genes), small N (samples)" phenomenon complicates the
      problem of microarray classification with logistic regression. The indeterminacy
      of the maximum likelihood solutions, multicollinearity of predictor variables and
      data over-fitting cause unstable parameter estimates. Moreover, computational
      problems arise due to the large number of predictor (genes) variables.
      Regularized logistic regression excels as a solution. However, the difficulties
      found here involve an objective function hard to be optimized from a mathematical
      viewpoint and a careful required tuning of the regularization parameters.
      METHODS: Those difficulties are tackled by introducing a new way of regularizing
      the logistic regression. Estimation of distribution algorithms (EDAs), a kind of
      evolutionary algorithms, emerge as natural regularizers. Obtaining the
      regularized estimates of the logistic classifier amounts to maximizing the
      likelihood function via our EDA, without having to be penalized. Likelihood
      penalties add a number of difficulties to the resulting optimization problems,
      which vanish in our case. Simulation of new estimates during the evolutionary
      process of EDAs is performed in such a way that guarantees their shrinkage while
      maintaining their probabilistic dependence relationships learnt. The EDA process
      is embedded in an adapted recursive feature elimination procedure, thereby
      providing the genes that are best markers for the classification. RESULTS: The
      consistency with the literature and excellent classification performance achieved
      with our algorithm are illustrated on four microarray data sets: Breast , Colon ,
      Leukemia and Prostate . Details on the last two data sets are available as
      supplementary material. CONCLUSIONS: We have introduced a novel EDA-based
      logistic regression regularizer. It implicitly shrinks the coefficients during
      EDA evolution process while optimizing the usual likelihood function. The
      approach is combined with a gene subset selection procedure and automatically
      tunes the required parameters. Empirical results on microarray data sets provide
      sparse models with confirmed genes and performing better in classification than
      other competing regularized methods.

PMID- 19387513
TI  - DCE-MRI data analysis for cancer area classification.
AB  - OBJECTIVES: The paper aims at improving the support of medical researchers in the
      context of in-vivo cancer imaging. Morphological and functional parameters
      obtained by dynamic contrast-enhanced MRI (DCE-MRI) techniques are analyzed,
      which aim at investigating the development of tumor microvessels. The main
      contribution consists in proposing a machine learning methodology to segment
      automatically these MRI data, by isolating tumor areas with different meaning, in
      a histological sense. METHODS: The proposed approach is based on a three-step
      procedure: i) robust feature extraction from raw time-intensity curves, ii) voxel
      segmentation, and iii) voxel classification based on a learning-by-example
      approach. In the first step, few robust features that compactly represent the
      response of the tissue to the DCE-MRI analysis are computed. The second step
      provides a segmentation based on the mean shift (MS) paradigm, which has recently
      shown to be robust and useful for different and heterogeneous clustering tasks.
      Finally, in the third step, a support vector machine (SVM) is trained to classify
      voxels according to the labels obtained by the clustering phase (i.e., each class
      corresponds to a cluster). Indeed, the SVM is able to classify new unseen
      subjects with the same kind of tumor. RESULTS: Experiments on different subjects
      affected by the same kind of tumor evidence that the extracted regions by both
      the MS clustering and the SVM classifier exhibit a precise medical meaning, as
      carefully validated by the medical researchers. Moreover, our approach is more
      stable and robust than methods based on quantification of DCE-MRI data by means
      of pharmacokinetic models. CONCLUSIONS: The proposed method allows to analyze the
      DCE-MRI data more precisely and faster than previous automated or manual
      approaches.

PMID- 19387517
TI  - Shift work and the risk of ischemic heart disease - a systematic review of the
      epidemiologic evidence.
AB  - OBJECTIVE: The objective of this review was to evaluate the epidemiologic
      evidence for a causal relation -between shift work and ischemic heart disease.
      METHODS: We conducted a systematic search until the end of March 2008 for studies
      providing information on the relative risk of ischemic heart disease in relation
      to shift work. The quality of included papers was evaluated with respect to
      design, exposure and outcome information, bias, and exposure response assessment.
      RESULTS: Relevant information was retrieved from 14 studies. Seven of these
      analyzed fatal events, six -combined fatal and non-fatal events, while one study
      reported separately on both types of events. Relative risks ranged from 0.6-1.4
      in 12 papers while two papers reported relative risks around 2.0. Most studies
      based on fatal events showed no or weak associations while studies that combined
      fatal and non-fatal events showed modest positive associations. In a majority of
      studies, we could not reasonably rule out negative or positive bias due to the
      quality of outcome or exposure information, or confounder control. Five studies
      used years in shift work for exposure response analysis and no consistent pattern
      were seen. CONCLUSION: There is limited epidemiological evidence for a causal
      relation between shift work and ischemic heart disease.

PMID- 19387518
TI  - [Perioperative management of patients with pacemakers and implantable
      cardioverter-defibrillators].

PMID- 19387520
TI  - Prediction of environmental properties in water-soil-air systems for phthalates.
AB  - In this paper, environmentally key properties including aqueous solubilities
      (S(W)), vapor pressures (V(P)), sorption coefficients (K(OC)), octanol-water
      (K(OW)), octanol-air (K(OA)) and air-water (K(AW)) partition coefficients of 53
      phthalates are studied by the quantitative structure-property relationship models
      by means of previously proposed Lu index. Reliable models are obtained to
      estimate Log S(W), solubility in air (Log S(A)), Log K(OC) and Log K(OW) for
      phthalates with the correlation coefficients of estimations (R) being 0.9869,
      0.9461, 0.8880 and 0.9836, and the standard errors being 0.44, 0.27, 0.52 and
      0.40, respectively. The predictive ability of the constructed models is
      demonstrated by the correlation coefficients (R(CV)) in the leave-one-out cross
      validation procedures being 0.9709, 0.9218, 0.8089 and 0.9784, and the
      corresponding standard errors (s(CV)) being 0.47, 0.34, 0.67 and 0.47,
      respectively. The properties of K(AO) and K(AW) for the phthalates are calculated
      by the predicted S(W), S(A), and K(OW) values.

PMID- 19387519
TI  - Bearing grudges and physical health: relationship to smoking, cardiovascular
      health and ulcers.
AB  - BACKGROUND: Personality traits are reported to be associated with a variety of
      medical comorbidities. Correlational studies report an association between
      'bearing grudges' and medical conditions. We hypothesize persons reporting
      "bearing grudges for years" would be more likely to have medical comorbidities
      and test this hypothesis in an epidemiological sample. METHODS: The National
      Comorbidity Survey Replication is a probability sample of the US population
      designed to constitute a nationally representative sample (N = 9,882).
      Associations were measured in odds ratios (95% CI) and adjusted using logistic
      regression. Confounders included: gender, age, race, and smoking status. We
      tested the hypothesis on 14 following medical conditions: heart disease, high
      blood pressure, history of heart attack, asthma, diabetes, cancer, epilepsy,
      arthritis, neck problems, headaches, stroke, and ulcers. Significance levels were
      adjusted for multiple comparisons using the Bonferoni procedure. RESULTS:
      Positive and statistically significant associations were found, after adjusting
      for confounders and correcting for multiple comparisons, between bearing grudges
      and history of heart attack (odds ratio 2.1, 95% CI 1.5-2.9) and disease (1.6,
      1.2-2.2); high blood pressure (1.5, 1.3-1.7), stomach ulcers (1.6, 1.3-1.9);
      arthritis (1.5, 1.3-1.9); back problems (1.6, 1.4-1.8); headaches (1.8, 1.6-2.1);
      and chronic pain (1.7, 1.4-2.1). No association was found with history of asthma,
      diabetes, epilepsy, allergies, stroke, and cancer. CONCLUSIONS: In a population
      based survey, bearing grudges is associated with a history of pain disorders,
      cardiovascular disease, and stomach ulcers. These results point to the importance
      of psychosomatic research in medical settings.

PMID- 19387521
TI  - Heavy metal uptake by Euplotes mutabilis and its possible use in bioremediation
      of industrial wastewater.
AB  - A ciliate protozoan, Euplotes mutabilis, isolated from heavy metal laden
      industrial wastewater, has been shown to tolerate multiple heavy metals thus
      suggesting its significance in bioremediation of industrial effluents. This
      ciliate tolerated Zn(2+) up to 33 microg/mL, Cd(2+) up to 22 microg/mL and Ni(2+)
      up to 18 microg/mL. The ciliate could uptake 85% Zn(2+), 84% of Cd(2+) and 87% of
      Ni(2+) after 96 h of inoculation of growth medium containing 10 microg/mL of
      Zn(2+) and 5 microg/mL of Cd(2+) and Ni(2+), with actively growing ciliates.
      After 6 days of incubation the ciliate removed 87% Cd(2+), 92% Ni(2+), and 93%
      Zn(2+) from the wastewater. The heavy metal uptake capability of Euplotes
      mutabilis may be employed for metal detoxification operations.

PMID- 19387522
TI  - Blood cholinesterases from Washington State orchard workers.
AB  - Court-ordered monitoring of blood cholinesterases (ChEs) from orchard workers in
      Washington State is underway. In 2008, the mean red blood cell
      acetylcholinesterase (AChE, EC 3.1.1.7) activity was 9.65 +/- 1.11
      micromoles/min/ml (n = 1,793) and the mean serum (BChE, 3.1.1.6) activity was
      5.19 +/- 0.90 micromoles/min/ml (n = 1,811). Determinations were made using the
      Ellman assay and automated equipment of Pathology Associates Medical Laboratories
      (PAML), Spokane, Washington.

PMID- 19387523
TI  - Mercury bio-concentration potential of Larch Bolete, Suillus grevillei, mushroom.
AB  - Larch Bolete can be classified as a mushroom species accumulating Hg in the
      fruiting bodies. Our results did indicate diversity of Hg concentrations (p <
      0.05), depending on a site of collection of Larch Bolete fruiting bodies as well
      as the lack of any statistically significant differences in soil mercury
      contamination among the examined sites. Values of 1.0 microg Hg/g dw for pool of
      caps and 2.0 microg/g dw for a single cap of Larch Bolete are suggested as
      threshold concentrations implying Hg baseline level, while greater value could
      imply contamination due to the site pollution.

PMID- 19387524
TI  - Effects of mercury released from gold extraction by amalgamation on renal
      function and environment in Shanxi, China.
AB  - We investigated the distribution of mercury and its impacts on the renal function
      of the residents living in mercury-contaminated area due to gold extraction by
      amalgamation in some area of Shanxi, China. The results showed that mercury
      concentrations in contaminated air in four seasons were 79-240 ng/m(3). The
      mercury concentration in the river across contaminated area was also high. The
      mercury contents in the grain were higher than those in the non-mercury
      contaminated area. The urinary mercury and urinary beta(2)-microglobulin for the
      residents living in the contaminated area were 1.24 +/- 3.80 microg/L and 228.98
      +/- 4.34 microg/g Cr, higher than those in the non-mercury contaminated area.

PMID- 19387525
TI  - Acetate enhances the specific consumption rate of toluene under denitrifying
      conditions.
AB  - Toluene is usually present in the environment as a contaminant along with other
      carbon sources which may influence its removal. In this work we studied the
      effect of a readily consumable carbon source such as acetate on toluene
      mineralization under denitrifying conditions. Continuous and batch cultures with
      stabilized denitrifying sludge were carried out. An upflow anaerobic sludge
      blanket reactor (UASB) was fed with several ratios of acetate-C/toluene-C loading
      rates (mg C/L-day: 100/0, 75/25, 50/50, and 0/100). Batch assays with different
      acetate-C/toluene-C ratios (10/70, 30/50, 50/30, and 65/20 mg C/L) were also
      done. As the acetate loading rate decreased in the culture, the carbon and
      nitrate consumption efficiency decreased by 40% and 34%, respectively. HCO(3) (-)
      and N(2) yields also decreased by 43%. Analysis of the denitrifying community
      using the denaturing gradient gel electrophoresis technique indicated that there
      was no clear relationship between its population profile and the metabolic
      pattern. In batch assays, when the acetate concentration was higher than that of
      toluene (65 mg acetate-C/L vs 20 mg toluene-C/L), the specific consumption rate
      of toluene (q(T)) was two times higher than in assays with 20 mg toluene-C/L as
      the sole electron source (0.006 mg C/mg volatile suspended solids-day). It is
      proposed that acetate can act by enhancing the growth of microbial populations
      and as a biochemical enhancer. The results show that acetate addition can be
      useful to improve the consumption rate of toluene in contaminated water.

PMID- 19387526
TI  - Validation of the pelvic organ prolapse quantification (POP-Q) system in left
      lateral position.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study is to examine the inter
      observer reliability of the pelvic organ prolapse quantification (POP-Q) system
      in left lateral position. METHODS: Women attending urogynaecology outpatient
      clinics were examined in the left lateral position using a digital examination
      and POP-Q. This was repeated separately by a second blinded clinician. The inter
      observer agreement was calculated using the Cohen's kappa coefficient. The POP-Q
      examination was then performed with a woman lying in dorsal lithotomy position.
      The POP-Q findings in the two positions were compared. RESULTS: Two hundred and
      eighteen women were recruited. The digital examination had a moderate inter
      observer reliability with a kappa value of 0.54. The POP-Q showed a high degree
      of reliability (0.88). There was a high degree of correlation between the POP-Q
      findings in left lateral and lithotomy position (rho > 0.95, p < 0.001).
      CONCLUSION: The POP-Q in the left lateral position is reliable, easy to perform,
      acceptable for patients, and is not a time-consuming examination.

PMID- 19387527
TI  - Bilateral multiple complex variations in the formation and branching pattern of
      brachial plexus.
AB  - Bilateral variations in the formation and branching of brachial plexus are
      extremely rare. Multiple bilateral variations in brachial plexus right from
      divisions to branching pattern were observed during the dissection in an adult
      male cadaver. Lateral and medial cord formation showed deviation from the usual
      pattern. Anterior division of upper trunk continued as lateral cord. Medial cord
      was formed by the union of anterior division of lower trunk and anterior division
      of middle trunk, thus receiving fibers from both the trunks. Anterior division of
      middle trunk bifurcated into upper and lower branches. We encountered two lateral
      roots bilaterally and two medial roots of median nerve on the left side with
      anomalous origin. There were three upper subscapular nerves on the left and two
      on the right side with variations in their origin. Anomalous origin of many other
      branches on both sides was encountered. It is extremely uncommon to find so many
      variations in one body and bilateral variations are still too rare. Understanding
      of such variations is clinically important for diagnosing unexplained clinical
      signs and symptoms as well as during nerve blocks and certain surgical procedures
      around the neck and proximal arm.

PMID- 19387528
TI  - Natural orifice surgery (NOTES) and biliary disease, is there a role?
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is a term
      coined by a joint group of surgeons and gastroenterologists organized by Society
      for American Gastrointestinal Endoscopic Surgeons (SAGES) and American Society of
      Gastroenterologists (ASGE) to describe the fusion of minimally invasive surgery
      and interventional endoscopy. METHODS: Current literature and compiled personal
      experience in NOTES was reviewed to provide an expert opinion on the role of
      NOTES in HPB surgery. RESULTS: The majority of experience obtained to date has
      been in animal models. The few human cases and clinical trials that have been
      performed show excellent promising outcomes with minimal morbidity. DISCUSSION:
      The merger of interventional endoscopy and minimally invasive surgery is a
      natural progression as we continually push the envelope of minimally invasive
      surgery. Endoscopic retrograde cholangiopancreatography, biliary stents and
      endoscopic ultrasonography have forever changed treatment algorithms in HPB
      surgery. Advancement of minimally invasive surgery to include the liver
      resections, pancreatic resections and pseudocyst management has improved
      morbidity and become the standard of care in many cases. Continued development of
      natural orifice techniques may further alter the approaches to the biliary tract,
      liver and pancreas.

PMID- 19387529
TI  - Safety of combined resection of the middle hepatic artery in right
      hemihepatectomy for hilar biliary malignancy.
AB  - BACKGROUND/PURPOSE: In patients with hilar biliary malignancies, preservation of
      the middle hepatic artery (MHA, segment IV artery) where it runs close to the
      tumor in the hepatic hilum may lead to resection with positive margins. This
      retrospective study assessed the safety of combined resection of the MHA with
      right hemihepatectomy, caudate lobectomy, and bile duct resection for hilar
      biliary malignancies. METHODS: Of 61 patients with hilar biliary malignancies who
      underwent right hemihepatectomy, we classified the branching patterns of the MHA
      according to the origins and courses in the hilum. The MHA was resected without
      reconstruction in 16 patients in whom the artery ran close to the tumor. We
      compared the perioperative outcomes in these patients with those of patients who
      did not undergo resection of the artery. RESULTS: Anatomically, the MHA ran on
      the right side of the umbilical portion of the portal vein in 40 (66%) patients.
      Perioperative data for the patients who underwent combined resection were similar
      to those in whom the MAH was preserved. There were no postoperative complications
      that could be directly related to the arterial resection. CONCLUSIONS: Combined
      resection of the MHA during right hemihepatectomy for hilar biliary malignancies
      has a safe perioperative course.

PMID- 19387530
TI  - A pancreaticoduodenectomy is acceptable for periampullary tumors in the elderly,
      even in patients over 80 years of age.
AB  - BACKGROUND: Although the mortality rates for pancreaticoduodenectomy have been
      reported to be low for periampullary tumors at high-volume centers, postoperative
      results still remain unclear for elderly patients over 80 years of age. METHODS:
      This was a retrospective study of patients who underwent a
      pancreaticoduodenectomy and consisted of 335 patients who were treated for
      periampullary tumors between January 1994 and August 2008. The main outcomes were
      postoperative complications, mortality, and the length of hospital stay among the
      elderly patients, and they were analyzed in three groups: elderly patients over
      80 years old, septuagenarians, and those under 70 years of age. RESULTS: The
      performance status of elderly patients was lower than that of the patients under
      70 (P < 0.05), and the elderly had a higher American Society of Anesthesiologists
      physical status classification score (P < 0.001) as well as low hemoglobin and
      serum albumin levels (P < 0.01 and P < 0.001, respectively). The incidence of
      delayed gastric emptying in the elderly was higher; however, there was no
      significant difference. The other outcomes in the elderly group were similar to
      those of the other groups. CONCLUSIONS: Pancreaticoduodenectomy was considered to
      be a feasible surgical procedure for elderly patients who had a good performance
      status.

PMID- 19387531
TI  - The impact of body mass index on laparoscopic cholecystectomy in Taiwan: an
      oriental experience.
AB  - BACKGROUND/PURPOSE: The outcome analysis of obese patients undergoing
      laparoscopic cholecystectomy (LC) in Asia-Pacific countries is rarely reported.
      This study examined associations between body mass index (BMI) and clinical
      outcomes of elective LC in Taiwan. METHODS: A total of 627 patients with
      gallbladder disease due to gallstones undergoing LC were divided into three
      groups based on BMI: <25.0 kg/m2 (normal, NO; n = 310), 25.0-29.9 kg/m2
      (overweight, OW; n = 252), and >30 kg/m2 (obese, OB; n = 65). RESULTS: Both
      overweight and obesity were not associated with conversion and complication
      rates. The conversion rates of the three groups were 5.5 (NO), 6.0 (OW), and 4.6%
      (OB), and the complication rates were 3.2 (NO), 2.4% (OW), and 4.6% (OB),
      respectively. However, overweight and obesity were related to a trend toward
      longer operating time (NO 67.4 +/- 31.8; OW 77.8 +/- 35.6; OB 79.0 +/- 37.9 min)
      (P trend <0.001). One death (BMI 40.6 kg/m2) was due to septic complications. In
      the multivariable logistic analysis, only acute cholecystitis, but not BMI, was a
      predictor for conversion and complications. CONCLUSIONS: Based on these results,
      it appears that BMI was not associated with clinical outcomes and that LC is a
      safe procedure in obese patients with uncomplicated gallstone disease in Taiwan.

PMID- 19387532
TI  - Usefulness of Sonazoid contrast-enhanced ultrasonography for hepatocellular
      carcinoma: comparison with pathological diagnosis and superparamagnetic iron
      oxide magnetic resonance images.
AB  - OBJECTIVE: We investigated the usefulness of Sonazoid contrast-enhanced
      ultrasonography (Sonazoid-CEUS) in the diagnosis of hepatocellular carcinoma
      (HCC). The examination was performed by comparing the images during the Kupffer
      phase of Sonazoid-CEUS with superparamagnetic iron oxide magnetic resonance (SPIO
      MRI). METHODS: The subjects were 48 HCC nodules which were histologically
      diagnosed (well-differentiated HCC, n=13; moderately differentiated HCC, n=30;
      poorly differentiated HCC, n=5). We performed Sonazoid-CEUS and SPIO-MRI on all
      subjects. In the Kupffer phase of Sonazoid-CEUS, the differences in the contrast
      agent uptake between the tumorous and non-tumorous areas were quantified as the
      Kupffer phase ratio and compared. In the SPIO-MRI, it was quantified as the SPIO
      intensity index. We then compared these results with the histological
      differentiation of HCCs. RESULTS: The Kupffer phase ratio decreased as the HCCs
      became less differentiated (P<0.0001; Kruskal-Wallis test). The SPIO-intensity
      index also decreased as HCCs became less differentiated (P<0.0001). A positive
      correlation was found between the Kupffer phase ratio and the SPIO-MRI index
      (r=0.839). In the Kupffer phase of Sonazoid-CEUS, all of the moderately and
      poorly differentiated HCCs appeared hypoechoic and were detected as a perfusion
      defect, whereas the majority (9 of 13 cases, 69.2%) of the well-differentiated
      HCCs had an isoechoic pattern. The Kupffer phase images of Sonazoid-CEUS and SPIO
      MRI matched perfectly (100%) in all of the moderately and poorly differentiated
      HCCs. CONCLUSION: Sonazoid-CEUS is useful for estimating histological grading of
      HCCs. It is a modality that could potentially replace SPIO-MRI.

PMID- 19387533
TI  - Preoperative serum gamma-glutamyl transferase to alanine aminotransferase ratio
      is a convenient prognostic marker for Child-Pugh A hepatocellular carcinoma after
      operation.
AB  - BACKGROUND: The ratio of serum gamma-glutamyl transferase (GGT) to alanine
      aminotransferase (ALT) is a parameter for assessing responses to antiviral
      therapies. The relationship between the prognosis of hepatitis B-associated
      hepatocellular carcinoma (HCC) and preoperative GGT/ALT is studied in
      hepatectomized Child-Pugh A patients. METHODS: Two hundred and nineteen patients
      with hepatitis B virus-related HCC were included. Serum ALT and GGT levels were
      examined preoperatively and the GGT/ALT ratios were calculated. Their prognostic
      capabilities were evaluated by Cox-regression model. RESULTS: As dichotomized
      variables, GGT and ALT were distributed unequally (P < 0.001). Most patients had
      high levels of GGT (n = 110) but low levels of ALT (n = 185). ALT displayed no
      relation to recurrence or survival, while GGT was independently associated with
      survival (P = 0.002). The GGT/ALT ratio could predict survival precisely either
      in a continuous or dichotomized fashion (P < 0.001 and 0.001, respectively), and
      also related to recurrence when dichotomized (P = 0.002). Additionally, high
      GGT/ALT ratio was associated with high early recurrence rates, more recurrence
      related deaths and various aggressive tumor characteristics such as larger tumor
      size, vascular invasion, poor encapsulation and advanced BCLC stage. In further
      stratified analyses, this ratio could discriminate the outcomes of patients with
      high- or low-alpha-fetoprotein level. CONCLUSIONS: The elevated GGT/ALT ratio was
      a promising predictor for poor prognosis of Child-Pugh A HCC patients after
      operation mainly through its tight relevance to the primary tumor burden.

PMID- 19387534
TI  - Factors contributing to antiviral effect of adefovir dipivoxil therapy added to
      ongoing lamivudine treatment in patients with lamivudine-resistant chronic
      hepatitis B.
AB  - PURPOSE: The antiviral effect of adefovir dipivoxil (ADV) added to ongoing
      lamivudine (LAM) treatment for LAM-resistant chronic hepatitis B (CHB) differs
      among patients. We investigated clinical factors affecting the response to ADV
      therapy in LAM-resistant CHB. METHODS: The subjects were 75 LAM-resistant CHB
      patients treated with ADV in addition to LAM. Virological response (VR) was
      defined as HBV DNA clearance (<2.6 logcopies/ml) at 12 months after the start of
      ADV therapy. Clinical factors contributing to VR were examined by univariate and
      multivariate analyses. RESULTS: Lower HBV DNA at baseline and negative hepatitis
      B e antigen (HBeAg) were significant factors affecting VR in univariate analysis.
      In multivariate analysis, lower HBV DNA at baseline (P = 0.005), negative HBeAg
      (P = 0.009), and higher ALT (P = 0.036) were significant independent factors
      contributing to VR. In HBeAg-positive patients, HBV DNA clearance was more
      frequently observed during ADV therapy in patients with baseline HBV DNA < or =
      7.0 logcopies/ml than in those with baseline HBV DNA >7.0 logcopies/ml. By
      contrast, the link of lower HBV DNA at baseline to better therapeutic response
      was not evident in HBeAg-negative patients. CONCLUSION: In ADV therapy added to
      ongoing LAM treatment for LAM-resistant CHB, lower baseline HBV DNA and negative
      HBeAg contributed to a better antiviral effect. Addition of ADV should be done
      promptly before marked increase in HBV DNA, especially in CHB patients showing
      LAM resistance positive for HBeAg.

PMID- 19387535
TI  - Influence of cranial morphology on the location of chronic subdural haematoma.
AB  - BACKGROUND: The purpose of the present study was to evaluate the relationship
      between cranial morphology and location of a chronic subdural haematoma (CSDH) in
      patients with and without intracranial vault asymmetry. METHOD: The study was
      conducted in 110 consecutive adult patients who underwent surgery for CSDH. The
      relationship between the following variables and CSDH was studied: sex, age, past
      medical history, history of trauma, interval between head injury and symptoms,
      clinical presentation, location of the CSDH, symmetry of the frontal and
      occipital intracranial vault on the CT scan and/or MR images, surgical treatment
      and outcome. Throughout the analysis, p < 0.05 was considered statistically
      significant. FINDINGS: The frontal cranial vault was symmetrical in 48 patients
      (43.6%) and asymmetrical in 62 patients (56.4%). CSDH was more commonly bilateral
      in patients with a symmetrical frontal cranial vault than those with an
      asymmetrical shape (41.7% vs 17.7% and this difference is statistically
      significant (p = 0.01). In 62 patients with an asymmetric frontal skull vault,
      the CSDH was bilateral in 11 patients. In the remaining 51 patients, the CSDH was
      located on the same side of the most curved frontal convexity in 34 patients and
      on the side of the less curved frontal convexity in 17 patients. The occipital
      cranial vault was symmetrical in 44 patients (40%) and asymmetrical in 66
      patients (60%). CSDH was more commonly bilateral in patients with a symmetrical
      occipital cranial vault than those with an asymmetrical one (40.9% vs 19.7%) and
      this difference was also statistically significant (p = 0.019). In 66 patients
      with an asymmetric occipital skull vault, the CSDH was bilateral in 13 patients.
      In the remaining 53 patients, the CSDH located on the same side of the most
      curved occipital convexity in 39 patients and on the side of the less curved
      occipital convexity in 14 patients. CONCLUSIONS: Frontal and occipital
      intracranial vault morphology provides valuable information about location of
      CSDH. Bilateral CSDH is common in patients with symmetrical frontal and occipital
      cranial vault. In asymmetrical cranium, CSDH usually locates on the same side of
      the most curved frontal or occipital convexity. Identification of this
      relationship can be very useful to elucidate the origin and the pathogenesis of
      CSDH.

PMID- 19387536
TI  - Outcome after emergency surgery without angiography in patients with
      intracerebral haemorrhage after aneurysm rupture.
AB  - BACKGROUND: Patients with large intracerebral haematomas (ICH) from aneurysm
      rupture often present in a poor clinical condition and have a poor prognosis.
      Time delay for preoperative angiography might in some cases be unappealing. We
      evaluated the outcome after immediate haematoma removal and aneurysm occlusion
      without preoperative angiography. METHODS: We retrospectively identified 13
      consecutive patients. We recorded clinical data and evaluated mortality and
      morbidity with the Glasgow Outcome Score (GOS) and Telephone Interview of
      Cognitive Status (TICS). FINDINGS: At follow up seven of thirteen patients had
      favourable outcome assessed by GOS. Three patients had severe disability and
      three patients died. None of the survived patients interviewed had impaired
      cognition. CONCLUSIONS: In patients presented in a critical state with aneurysmal
      ICH, emergency haematoma removal and aneurysm clipping without the delay for
      diagnostic angiography may be life saving and a satisfactory outcome can be
      accomplished.

PMID- 19387537
TI  - Polysialic acid overexpression in malignant astrocytomas.
AB  - OBJECTIVE: Polysialic acid (PSA) is a carbohydrate binding on the neural cell
      adhesion molecule NCAM and impedes cell-cell interactions. It prevents neural
      progenitor cell differentiation and promotes their migration. Highly malignant
      tumours like small cell lung carcinoma (SCLC) also overexpress PSA and this
      correlates with a negative prognosis. METHODS: Intra-operatively collected
      biopsies from 30 patients with different astrocytoma grades were immuno
      histochemically examined to identify expression of PSA. RESULTS: Astrocytoma
      grade I and II had 4% PSA expressing cells whereas in grade III and IV the number
      of PSA expressing cells was 45%. This difference was statistically highly
      significant. CONCLUSION: In this short communication we show that highly
      malignant astrocytomas express significantly more PSA compared to less malignant
      astrocytomas. Cleavage of PSA could be used in future therapeutic approaches.

PMID- 19387538
TI  - Clinical course of abducens nerve palsy associated with skull base tumours.
AB  - BACKGROUND: The clinical course of abducens nerve palsy associated with skull
      base tumour is rarely reported. In this study, we examined the post-operative
      course of abducens nerve palsies associated with various skull base tumours.
      METHOD: Between January 2003 and December 2006, 240 patients with various skull
      base tumours underwent surgery at Kyushu University Hospital. Among them, nine
      patients presented with abducens nerve palsies (ten nerves) following surgery.
      The conditions included two pituitary adenomas, two trigeminal schwannomas and
      five meningiomas. We evaluated the function of the abducens nerves in these
      patients on admission, at discharge, and periodically in the outpatient clinic.
      FINDINGS: Four of the abducens nerve palsies already existed prior to surgery,
      and six of them developed post-operatively. In the four patients with pituitary
      adenomas and trigeminal schwannomas, all nerves were anatomically preserved and
      showed complete recovery of function within 6 months after surgery. In contrast,
      only two of the six palsies in patients with skull base meningiomas showed
      complete recovery. In three patients with petro-clival meningiomas, the abducens
      nerves were completely transected during surgery, and one was reconstructed using
      fibrin glue. This patient remarkably recovered from the abducens nerve palsy
      within 2 years. CONCLUSIONS: The abducens nerve palsies in pituitary adenomas and
      trigeminal schwannomas showed a better clinical course compared to those in skull
      base meningiomas. The abducens nerve palsies that occur with skull base
      meningiomas are less likely to recover. Nevertheless, it is important to preserve
      the nerves and to perform surgical repair if the nerve is transected.

PMID- 19387539
TI  - Occipital inter-hemispheric approach for lateral ventricular trigone meningioma.
AB  - OBJECTIVE: The optimal surgical approach for a trigone meningioma is still
      controversial. Here, we report two patients with trigone meningioma treated
      successfully via an occipital inter-hemispheric and trans-cortical approach in
      the lateral semi-prone position. CLINICAL PRESENTATION: A 53-year-old woman was
      admitted to a local hospital with sudden transient dizziness and vomiting. The CT
      brain scan demonstrated a right intra-ventricular tumour. She was therefore
      transferred to our hospital for surgical treatment. The other patient was a 67
      year-old woman who was admitted to a local hospital after a traffic accident and
      a CT brain scan revealed an incidental right intra-ventricular tumour. After
      referral to our hospital, periodic MRI examinations revealed gradual tumour
      enlargement within a one-year period. Neither of the patients had any
      neurological deficits, including in the visual fields. INTERVENTION: The head of
      each patient was positioned so that the tumour-containing right ventricle was
      oriented downwards and laterally. An occipital inter-hemispheric approach was
      performed and using a navigation system, the tumour was identified about 1 cm in
      depth from the cortical surface. After the medial part of the tumour was
      debulked, the posterior and then the anterior choroidal blood supplies to the
      tumour were identified. Occlusion of these vessels achieved tumour haemostasis.
      The tumours were totally removed via a 1.5-cm cortical incision. Brain retraction
      was minimal because the right hemisphere was pulled down by gravity. Therefore,
      the para-splenial cisterns were easily accessed, resulting in early release of
      cerebrospinal fluid. Post-operative MRI showed complete removal of the tumour and
      the patients had no neurological deficits. Anti-epileptic medication was
      withdrawn one week after the operation. CONCLUSIONS: The occipital inter
      hemispheric fissure lacks important bridging veins. The approach used and patient
      positioning minimized damage to the lateral aspect of the optic radiation and the
      corpus callosum. Except in patients with very large trigone meningiomas, this
      approach is useful for decreasing the risk of post-operative hemianopsia or
      epilepsy, and possibly speech disturbance, even in patients with a tumour in the
      dominant hemisphere.

PMID- 19387540
TI  - Arachnoid cysts of the fourth ventricle - short illustrated review.
AB  - Arachnoid cysts are frequent anomalies of the CNS. They are benign lesions within
      the arachnoid membrane and have been reported to occur in virtually all locations
      where arachnoid is present. An intraventricular location, however, is rare and
      occurrence within the fourth ventricle is particularly uncommon. The first report
      was published in 1979 on a paediatric patient. Since then, only a few further
      examples have been reported. Most of these patients presented with hydrocephalus.
      Shunting procedures were performed, but did not afford long-term improvement of
      symptoms. Definitive treatment consisted of open resection of the cyst-wall. We
      report a 34-year-old woman with a large arachnoid cyst within the fourth
      ventricle who suffered from progressive cerebellar dysfunction. MRI showed
      massive enlargement of the fourth ventricle by an intraventricular arachnoid cyst
      which contained multiple septations. Complete excision of the cyst was necessary
      to reinstitute free CSF-flow and was performed via a median suboccipital
      approach. This report gives an overview of examples published to date and
      discusses pathogenesis and clinical features of arachnoid cysts in this location
      as well as operative strategies including neuroendoscopic techniques.

PMID- 19387541
TI  - Neurocytoma of the spinal cord: report of three cases and review of the
      literature.
AB  - The spinal cord is a very rare location for extra-ventricular neurocytomas.
      Composed of small round cells with neuronal differentiation, neurocytoma has a
      particularly favourable prognosis. Long disease-free intervals have been observed
      in patients who received sub-total removal and radiotherapy. A careful intra
      operative frozen section examination is helpful in avoiding excessive surgical
      tissue disturbance and to identify the best treatment option. To date, eight
      cases of neurocytoma of the spinal cord have been described. We report three more
      patients; one with very long survival, and review the published literature for
      this condition.

PMID- 19387542
TI  - Microscope and endoscopic pituitary surgery.
AB  - Having just celebrated the centenary of the first transsphenoidal pituitary
      operation by (Schloffer in Austria in Beitr Klin Chir 50:767-817, 1906), and this
      year the quarter centenary of the first published report of a therapeutic use of
      the neuroendoscope (for colloid cysts of the third ventricle) (Powell et al. in
      Neurosurgery 13:234-237, 1983), it is time to consider the relative merits of
      microscopic and endoscopic approaches for pituitary surgery. Although
      transsphenoidal endoscopic surgery has only been utilised by pioneers such as Jho
      since the mid-1990s (Jho et al., 1996), there is no doubt that it has already
      gained an important place in the neurosurgical armamentarium, but there is both
      confusion and propaganda about which method of surgery has most to offer, and
      indeed whether or not there is any real difference at all.

PMID- 19387543
TI  - Endoplasmic reticulum in the penumbra following middle cerebral artery occlusion
      in the rabbit.
AB  - Caspase-12 has been localized to endoplasmic reticulum (ER) and showed to involve
      ER stress-induced apoptosis. In the present work we investigated the
      temporospatial alterations of caspase-12 immunoreactivity in the penumbra
      following cerebral ischemia/reperfusion in rabbit. Transient cerebral ischemia
      was produced by intraluminal occlusion of the middle cerebral artery for 2 h
      followed by 1 h, 6 h, 1 day, 3 days, 7 days and 14 days of reperfusion. Caspase
      12 immunohistochemistry was first increased in the penumbra 1 h after
      reperfusion, with a peak at day 1 to day 3, and then gradually decreased to basal
      level at day 14. The number of TUNEL-positive cells and ultrastructural
      observation of brain sections in the penumbra showed a similar change at the same
      time points. ER mediated by caspase-12 participated in apoptosis induced by
      cerebral ischemia/reperfusion injury, which may provide a new area for
      therapeutic intervention to ameliorate outcomes following cerebral ischemia.

PMID- 19387544
TI  - Can demographic and admission laboratory variables be useful to identify long
      stay patients with acute ischemic stroke? A hospital-based cohort study in
      Singapore.
AB  - The demographic and laboratory predictors of long-stay patients with ischemic
      stroke were sought in this retrospective hospital-based study. In the univariate
      and multivariate analysis, advanced age, male gender, leukocytosis, elevated
      creatinine, low-serum albumin, elevated alkaline transaminases, and lactate
      dehydrogenase were identified as independent predictors of "long" stayers. At an
      optimal probability cut-offs, the receiver operating curve incorporating these
      variables was 0.70, sensitivity 68%, specificity 80%, positive-predictive value
      39% and negative-predictive value 95%. Application of this information may assist
      physicians to triage patients at risk of severe stroke for early therapy and
      care.

PMID- 19387546
TI  - Functions of mitochondria: from intracellular power stations to mediators of a
      senescence program.
AB  - In 1950 s I started in science by showing that non-phosphorylating respiration is
      critical for survival of an animal at low temperature. Later, in the 1960 s and
      1970 s, I took part in verification of Mitchell's chemiosmotic hypothesis
      postulating that (i)mitochondria transform energy of respiration to electricity
      and (ii) uncoupling of respiration represents discharge of this electricity by
      H(+) cycling. Fifteen years ago I turned to a specific kind of mitochondrial
      respiration which produces O(2)(-.), and I came to the conclusion that it plays
      an ominous role, killing mitochondria, cells, or even organisms. My present task
      is a "megaproject" with an ambitious goal of minimizing the damaging effect of
      O(2)(-.) and stopping senescence.

PMID- 19387545
TI  - Long-term results of immunomodulatory treatment in children and adolescents with
      multiple sclerosis: the Italian experience.
AB  - The main objective of this study is to evaluate the effect of immunomodulatory
      agents (IMAs) (Interferon-Beta, Glatiramer Acetate) in a large cohort of multiple
      sclerosis (MS) patients with disease onset in childhood or adolescence, treated
      before 16 years of age, after a long-term follow-up. A total of 130 patients were
      identified, 77 were treated with Avonex, 39 with Rebif/Betaferon, 14 with
      Copaxone. After a mean (SD) treatment duration of 53.6 +/- 27.0, 59.9 +/- 39.5
      and 74.6 +/- 35.5 months, respectively, the relapse rate decreased significantly.
      The final EDSS score was unchanged with respect to the initial score. Similar
      results were also observed in subjects who continued a long-term follow-up after
      they were included in an observational study in 2004, and in subjects who were
      treated before 12 years of age. The frequency of clinical and laboratory adverse
      events was similar to that observed in adult patients. To conclude, IMAs were
      effective and well tolerated in paediatric patients with MS.

PMID- 19387547
TI  - Protein kinase CK2 in health and disease: Structural bases of protein kinase CK2
      inhibition.
AB  - Protein kinase CK2 is involved in many fundamental aspects of normal cell life,
      but it is also able to establish favourable conditions for tumorigenesis. CK2 is
      elevated in various cancers, it is a potent suppressor of apoptosis, it strongly
      promotes cell survival, it strengthens the multi-drug resistant phenotype and can
      be considered a valuable drug target for cancer therapy. In this review, the
      structural bases of CK2 inhibition deduced from the analysis of crystal
      structures of CK2alpha-inhibitor complexes are presented and discussed. The best
      ATP-competitive inhibitors show an adequate hydrophobic character, an excellent
      shape complementarity with the unique active site of CK2, and the ability to
      establish polar interactions with both the hinge region and the positive
      electrostatic area near the conserved water W1 and the Lys68-Glu81 salt bridge.
      The state of the art of non-ATP-competitive inhibitors is also presented.

PMID- 19387550
TI  - Protein kinase CK2 in health and disease: CK2: the kinase controlling the Hsp90
      chaperone machinery.
AB  - CK2 is a ubiquitous and essential protein kinase with pleiotropic substrates and
      function, but it remains unclear how, when, and where CK2 activity is regulated
      in cells. Hsp90 is a major molecular chaperone that is required for the folding
      and function of its client proteins. A complex containing Hsp90 and its client
      protein includes co-chaperones such as steroid hormone receptor-specific FKBP52
      and signaling kinase-specific Cdc37. Co-chaperones work cooperatively with Hsp90
      to stabilize client proteins and to keep them in a conformation amenable to
      activation under appropriate conditions. In this review, critical roles of CK2 in
      the regulation of the Hsp90-mediated chaperone system are described. CK2
      phosphorylates and modulates Hsp90 and its co-chaperones FKBP52 and Cdc37. CK2
      dependent phosphorylation of Cdc37 is essential for the chaperoning function of
      Hsp90-Cdc37 for multiple signaling protein kinases. The tumor kinome appears to
      become addicted to the Hsp90-Cdc37 chaperone system, thus, targeting Hsp90,
      Cdc37, and CK2 is a promising strategy for cancer treatment.

PMID- 19387548
TI  - Protein kinase CK2 in health and disease: CK2: a key player in cancer biology.
AB  - Elevated levels of protein kinase CK2 (formerly casein kinase 2 or II) have long
      been associated with increased cell growth and proliferation both in normal and
      cancer cells. The ability of CK2 to also act as a potent suppressor of apoptosis
      offers an important link to its involvement in cancer since deregulation of both
      cell proliferation and apoptosis are among the key features of cancer cell
      biology. Dysregulated CK2 may impact both of these processes in cancer cells. All
      cancers that have been examined show increased CK2 expression, which may also
      relate to prognosis. The extensive involvement of CK2 in cancer derives from its
      impact on diverse molecular pathways controlling cell proliferation and cell
      death. Downregulation of CK2 by various approaches results in induction of
      apoptosis in cultured cell and xenograft cancer models suggesting its potential
      as a therapeutic target.

PMID- 19387549
TI  - Protein kinase CK2 in health and disease: CK2 and its role in Wnt and NF-kappaB
      signaling: linking development and cancer.
AB  - CK2 is a highly conserved tetrameric serine/ threonine kinase present in all
      eukaryotic organisms. It is constitutively active, and appears to be regulated by
      level of expression and activity, and subcellular localization. In turn, it has
      been postulated to control the function of many proteins through changes in
      phosphorylation that affect protein stability, protein-protein interactions, and
      subcellular localization. Through these mechanisms, CK2 regulates many
      fundamental cellular properties. An enzyme that carries out such a master
      regulatory function is likely to be important in organismic development and in
      cancer. We have shown that overexpression of CK2 catalytic subunits is capable of
      promoting tumorigenesis, and that loss of CK2 catalytic subunits in development
      can be lethal. Through studies in cells, mice, and frogs, we and others have
      identified the Wnt and NF-kappaB pathways as two key signal transduction pathways
      that are regulated by CK2 activity, in embryonic development and in cancer. These
      results suggest that inhibiting CK2 could be useful in treating cancer, but
      dangerous to developing organisms.

PMID- 19387551
TI  - Protein kinase CK2 in health and disease: Cellular functions of protein kinase
      CK2: a dynamic affair.
AB  - Protein kinase CK2 targets a vast array of substrates located in a number of
      cellular compartments, making the challenge of discriminating among these
      substrates a daunting task. However, as a signaling protein, CK2 could be
      targeted to different cellular compartments in response to various stress stimuli
      such as heat shock, UV irradiation, hypoxia, DNA damage and viral infections.
      This review will be focused on the evidence that the dynamic association of CK2
      subunits and the substrate-dependent subcellular targeting of the enzyme are a
      likely point of regulation in response to a variety of signaling events. We
      propose that in addition to enzymatic substrate recognition, regulated CK2
      localization to specific compartments should help to provide the exquisite
      specificity required for robust signal transduction.

PMID- 19387552
TI  - Protein kinase CK2 in health and disease: From birth to death: the role of
      protein kinase CK2 in the regulation of cell proliferation and survival.
AB  - Protein kinase CK2 is a serine/threonine kinase with a multitude of protein
      substrates. The enzyme is ubiquitously expressed in mammalian cells, where it
      functions in a variety of cellular processes, including cell cycle progression,
      apoptosis, transcription, and viral infection. While the importance of CK2 in the
      mammalian life cycle is undisputed, the regulatory mechanisms coordinating its
      numerous functions remain elusive. In this review, we focus on the various roles
      of CK2 in the mammalian cell, with particular attention on its functions through
      the stages of the cell cycle and during the decision to undergo cell death. We
      highlight how these roles are controlled in part through direct transcriptional
      regulation by CK2, and how the constitutive activity of CK2 can be hijacked in
      the case of viral infection. Finally, we discuss possible ways in which these
      functions are integrated to allow the cell to respond appropriately in the
      presence of multiple signals.

PMID- 19387553
TI  - Protein kinase CK2 in health and disease: Protein kinase CK2: from structures to
      insights.
AB  - Within the last decade, 40 crystal structures corresponding to protein kinase CK2
      (former name 'casein kinase 2'), to its catalytic subunit CK2alpha and to its
      regulatory subunit CK2beta were published. Together they provide a valuable, yet
      by far not complete basis to rationalize the biochemical features of the enzyme,
      such as its constitutive activity, acidophilic substrate specificity, dual
      cosubstrate specificity and its heterotetrameric quarternary structure.
      Comprehensive sets of structural superimpositions reveal that both CK2alpha and
      CK2beta are relatively rigid molecules. In CK2beta the critical region of
      CK2alpha recruitment is pre-formed in the unbound state. In CK2alpha the
      activation segment - a key element of protein kinase regulation - adapts
      invariably the typical conformation of the active enzymes. Recent structures of
      human CK2alpha revealed a surprising plasticity in the ATP-binding region,
      suggesting an alternative mode of activity control.

PMID- 19387554
TI  - Protein kinase CK2 in health and disease: Protein kinase CK2: an ugly duckling in
      the kinome pond.

PMID- 19387555
TI  - Tryptophan synthase: a mine for enzymologists.
AB  - Tryptophan synthase is a pyridoxal 5'-phosphate-dependent alpha(2)beta(2) complex
      catalyzing the last two steps of tryptophan biosynthesis in bacteria, plants and
      fungi. Structural, dynamic and functional studies, carried out over more than 40
      years, have unveiled that: (1) alpha- and beta-active sites are separated by
      about 20 A and communicate via the selective stabilization of distinct
      conformational states, triggered by the chemical nature of individual catalytic
      intermediates and by allosteric ligands; (2) indole, formed at alpha-active site,
      is intramolecularly channeled to the beta-active site; and (3) naturally
      occurring as well as genetically generated mutants have allowed to pinpoint
      functional and regulatory roles for several individual amino acids. These key
      features have made tryptophan synthase a text-book case for the understanding of
      the interplay between chemistry and conformational energy landscapes.

PMID- 19387556
TI  - Suppression of in vivo tumor growth by using a biodegradable thermosensitive
      hydrogel polymer containing chemotherapeutic agent.
AB  - Current systemic chemotherapy in the treatment of solid tumors inevitably induces
      various systemic adverse effects. Locally injected chemotherapy is expected to
      overcome this limitation of systemic therapy. We evaluated by luminescence
      imaging the effects of chemotherapy administered locally by means of a
      biodegradable thermosensitive hydrogel polymer. The human gastric cancer cell
      line HSC44Luc was used for tumor induction, and it was confirmed to be sensitive
      to doxorubicin by MTT assay. Cells were injected subcutaneously into Balb/c-nude
      mice. When the mean volume of tumor reached 400 mm(3), we divided the mice into 6
      groups (5 per group) according to treatment: 1) control (intratumor injection of
      PBS), 2) systemic injection of doxorubicin, 3) intratumor injection of polymer
      gel, 4) intratumor injection of polymer gel physically mixed with a low dose of
      doxorubicin, 5) intratumor injection of polymer gel physically mixed with a high
      dose of doxorubicin, 6) intratumor injection of conjugated polymer gel with
      doxorubicin. Body weight and tumor volume were measured every 2 or 3 days for 30
      days after treatment. One mouse in each group was sacrificed for histopathologic
      examination every week. Reductions in body weight were not significantly
      different among groups. The relative rate of tumor growth was 774% in Group 1,
      267% in Group 2, 813% in Group 3, -186% in Group 4, and 155% in Group 6,
      respectively. Thus the relative rate of tumor growth in the groups treated with
      polymer gel mixed with doxorubicin and the groups treated with conjugated polymer
      gel with doxorubicin were lower than that in the control group. Locally
      injectable chemotherapy using a thermosensitive hydrogel polymer with doxorubicin
      can suppress tumor growth effectively without severe systemic toxicity.

PMID- 19387558
TI  - Field applications of a bio-trickling filter for the removal of nitrogen oxides
      from flue gas.
AB  - A bio-trickling filter (BTF) packed with polyhedral spheres was used to remove
      nitrogen oxides (NOx) from the flue gas of a coal-fired power plant. The BTF
      system consistently removed 64-95% of the NOx after start-up and acclimation
      under dynamic conditions (e.g., 120-240 m(3)/h flue gas flow rate and inlet 300
      900 mg NOx/m(3)). Scanning electron microscopy of the biofilms that were formed
      showed a shift in the predominating bacteria. Analyses by PCR-denaturing gradient
      gel electrophoresis showed that the naturally-selected mixed cultures in the
      biofilm under a flue gas environment were mainly Klebsiella sp. and Pseudomonas
      sp.

PMID- 19387557
TI  - Genetically engineered T cells to target EGFRvIII expressing glioblastoma.
AB  - Glioblastoma remains a significant therapeutic challenge, warranting further
      investigation of novel therapies. We describe an immunotherapeutic strategy to
      treat glioblastoma based on adoptive transfer of genetically modified T
      lymphocytes (T cells) redirected to kill EGFRvIII expressing gliomas. We
      constructed a chimeric immune receptor (CIR) specific to EGFRvIII, (MR1-zeta).
      After in vitro selection and expansion, MR1-zeta genetically modified primary
      human T-cells specifically recognized EGFRvIII-positive tumor cells as
      demonstrated by IFN-gamma secretion and efficient tumor lysis compared to control
      CIRs defective in EGFRvIII binding (MRB-zeta) or signaling (MR1-delzeta). MR1
      zeta expressing T cells also inhibited EGFRvIII-positive tumor growth in vivo in
      a xenografted mouse model. Successful targeting of EGFRvIII-positive tumors via
      adoptive transfer of genetically modified T cells may represent a new
      immunotherapy strategy with great potential for clinical applications.

PMID- 19387559
TI  - [Diabetes type II - a surgical disease? From bed to research].

PMID- 19387560
TI  - [The curriculum for rotation physicians within the CHIR-Net].
AB  - INTRODUCTION: CHIR-Net is a German national surgical network for clinical trials.
      It is supported by the Federal Ministry for Education and Research (BMBF
      01GH0605) to establish infrastructure and expertise in the conduct of clinical
      trials within the surgical disciplines. An important aspect of this network is a
      qualified advanced training for physicians deployed at the CHIR-Net as part of a
      job rotation. METHODS: A catalog of activities for the time of rotation within
      the network has been developed in cooperation with the CHIR-Net, the deployed
      physicians and cooperating regional clinical trials centers (ZKS/KKS). RESULT:
      The focal points of the physicians' rotation in the CHIR-Net are outlined in a
      curriculum that has been established and evaluated in the network since January
      2008. CONCLUSION: After the rotation time at the CHIR-Net the skilled physicians
      act as multipliers of specialized knowledge on clinical research. In this way the
      acquired expertise will be transferred into clinical practice and treatment of
      patients within research projects will benefit directly.

PMID- 19387561
TI  - [Perianal fistulas in Crohn's disease: treatment results at an interdisciplinary
      unit].
AB  - BACKGROUND: Approximately one third of patients with Crohn's disease develop
      perianal fistulas. This study was conducted to determinate outcome predictors in
      patients treated at a specialized multidisciplinary unit. PATIENTS AND METHODS:
      Between May 2005 and May 2008, all patients with perianal Crohn's fistulas were
      treated by the same surgeon and a gastroenterologist specialized in managing
      patients with Crohn's disease. Deep fistulas were treated by fistulotomy. For
      high fistulas, a noncutting seton was placed followed by maintenance treatment
      with azathioprine and/or infliximab. "Optimal outcome" was recorded when (a)
      there was no need for diverting stoma, (b) complete healing was achieved by
      fistulotomy, or (c) fistula symptoms were under control, i.e. there was no need
      for treatment extension during follow-up. RESULTS: Thirty-four male and 32 female
      patients underwent 100 surgical interventions. The most frequent types of fistula
      were high trans-sphincteric (62%) and high intersphincteric (15%). Eleven of the
      32 females presented with rectovaginal fistulae. At the study end, complete
      healing was observed in 12 patients and 32 had good control of fistula symptoms.
      Seven required proctectomy, fistula symptoms were not under control in 12, and
      three required diverting stoma. Altogether 44 patients (67%) achieved optimal
      outcome. The following factors were predictors of nonoptimal outcome by
      multivariate analysis: presence of Crohn's colitis (P=0.01), age at the onset of
      Crohn's disease <20 years (P=0.02), and types of fistula not suitable for
      fistulotomy (P=0.05). CONCLUSIONS: The multidisciplinary approach at specialized
      units will lead to successful outcome in >60% of patients with Crohn's perianal
      fistulas. The presence of Crohn's colitis, young age at disease onset, and
      presence of high fistulas are indicators of poor prognosis.

PMID- 19387563
TI  - [Diseases of the hip joint. An important field of application for radiologists].

PMID- 19387562
TI  - [Pain and dysesthesia following total extraperitoneal hernia repair].
AB  - INTRODUCTION: Minimally invasive repair with alloplastic material for inguinal
      hernia has become a method with few complications and a low recurrence rate.
      Persistent pain and dysesthesia years after the procedure are however of growing
      clinical interest. It is still unknown to what degree initial pain or dysesthesia
      change in the long term. Therefore this study was done to evaluate patient
      complaints following total extraperitoneal repair (TER) over a long observation
      period. MATERIALS AND METHODS: Included in the study were patients from January
      2000 to December 2006 who were treated electively for uni- or bilateral inguinal
      hernia using TER. Exclusion criteria were emergency procedures, incarcerated
      hernia, and scrotal hernia. The patient data were collected using a prospective
      online data system and evaluation of long-term results via standardized
      questionnaires determining persisting pain, dysesthesia, physical limitations
      from the surgery, satisfaction with the operation, and recurrences. The patients
      were grouped according to length of follow-up after surgery: 12-36 months (group
      1), 37-60 months (group 2), and 61-96 months (group 3). RESULTS: Since January
      2000, 484 patients 18 to 97 years old with 620 inguinal hernias were operated. Of
      those, 349 were evaluated for this study (proportion of returned questionnaires:
      72.1%). No significant differences were noted in patient characteristics or early
      postoperative complications. The percentage of patients suffering from relevant
      pain (moderate to severe) dropped significantly: 10.3% (group 1) vs 1.0% (group
      2) (P<0.05) and 3.4% (group 3) (P<0.05). No significant differences were found
      concerning dysesthesia (19.6% in group 1 vs 19.2% in group 3). There were no
      significant differences in satisfaction with the operation, as 73.8% in group 1,
      67.7% in group 2, and 73.3% in group 3 were very satisfied with the results. The
      number of recurrences increased during the observation period: 1.9% in group 1,
      3.1% in group 2, and 5.5% in group 3 (P>0.05). CONCLUSIONS: Total extraperitoneal
      repair is a reliable method with low recurrence rate and high patient
      satisfaction. A relevant proportion of patients complain however of pain and
      dysesthesia persisting over years. The data from this study show that in the long
      term, pain incidence drops significantly while the rate of dysesthesia remains
      constant. Long follow-up is needed to evaluate the long-term course of persistent
      pain. For more precise understanding of the long-term results of herniotomy,
      prospective randomized studies are needed with accordingly long follow-up.

PMID- 19387564
TI  - [Imaging of hip joint arthroplasty].
AB  - The hip joint is the largest joint in the human body and consequently, its
      evaluation by diagnostic imaging is highly important. This includes imaging of
      hip joint arthroplasty, which is used to avoid joint immobility following a wide
      spectrum of diseases, such as end-stage degenerative disease, avascular necrosis
      of the femoral head or post-traumatic fractures. Conventional radiography is
      still the standard imaging modality for the evaluation of hip arthroplasty both
      directly following surgery and for periodical follow-up. In the majority of cases
      conventional radiography enables adequate assessment of early and late
      complications that can arise following hip arthroplasty, such as loosening,
      prosthetic or periprosthetic fracture, luxation, infection and soft tissue
      calcification. If the diagnosis cannot be established by means of radiography,
      advanced imaging methods such as computed tomography (CT) and magnetic resonance
      imaging (MRI), with or without injection of contrast media, may provide
      additional information. This is particularly true for the depiction of
      inflammatory processes. Regardless of the imaging modality used patients'
      clinical symptoms must also be taken into account in order to establish the
      correct diagnosis.

PMID- 19387565
TI  - Analysis of two promoters that control the expression of the GTP cyclohydrolase I
      gene in Drosophila melanogaster.
AB  - GTP cyclohydrolase I (GTPCH) is a key enzyme in the de novo synthesis of
      tetrahydrobiopterin. Previously, the Drosophila melanogaster GTPCH gene has been
      shown to be expressed from two different promoters (P1 and P2). In our study, the
      5'-flanking DNA regions required for P1 and P2 promoter activities were
      characterized using transient expression assay. The DNA regions between -98 and
      +31, and between -73 and +35 are required for efficient P1 and P2 promoter
      activities, respectively. The regions between -98 and -56 and between -73 and -41
      may contain critical elements required for the expression of GTPCH in Drosophila.
      By aligning the nucleotide sequences in the P1 and P2 promoter regions of the
      Drosophila melanogaster and Drosophila virilis GTPCH genes, several conserved
      elements including palindromic sequences in the regions critical for P1 and P2
      promoter activities were identified. Western blot analysis of transgenic flies
      transformed using P1 or P2 promoter-lacZ fusion plasmids further revealed that P1
      promoter expression is restricted to the late pupae and adult developmental
      stages but that the P2 promoter driven expression of GTPCH is constitutive
      throughout fly development. In addition, X-gal staining of the embryos and
      imaginal discs of transgenic flies suggests that the P2 promoter is active from
      stage 13 of embryo and is generally active in most regions of the imaginal discs
      at the larval stages.

PMID- 19387566
TI  - Decreased percentages of the peripheral blood T-cell subsets and the serum IL-2
      contents in chickens fed on diets excess in fluorine.
AB  - Three hundred 1-day-old Avian broilers were divided into four groups and fed on
      control diet (F 23 ppm) and high-fluorine diets (400 ppm, high-fluorine group I;
      800 ppm, high-fluorine group II; 1,200 ppm, high-fluorine group III) for 42 days
      (n=75/group). The percentages of CD4+ and CD8+ T cells were decreased in three
      high-fluorine groups when compared with those of control group. Meanwhile, the
      CD4+/CD8+ ratio were lower in high-fluorine group II at 28 days of age and in
      high-fluorine group III at 42 days of age than in control group. Also, the serum
      interleukin-2 (IL-2) contents were decreased in three high-fluorine groups when
      compared with those of control group. Histopathologically, the thymus became
      hypocellular in three high-fluorine groups. It was concluded that dietary
      fluorine excess (400~1,200 ppm) reduced the percentages of T-lymphocyte subsets
      and the serum IL-2 contents, and cellular immune function could be affected in
      chickens.

PMID- 19387567
TI  - Selenoprotein W modulates control of cell cycle entry.
AB  - The present study was conducted to identify targets of selenium (Se) provided to
      cultured human cells in physiologically relevant doses and forms. Breast and
      prostate epithelial cells were supplemented with Se provided as 100 nM sodium
      selenite or high-Se serum and gene expression was profiled with DNA microarrays.
      Pure sodium selenite affected expression of 560 genes in MCF-10A breast cells,
      including 60 associated with the cell cycle (p = 2.8 x 10(-16)). Selenoprotein W
      (SEPW1) was the only selenoprotein messenger RNA (mRNA) increased by both sodium
      selenite (specific) and high-Se serum (physiologic). SEPW1 small interfering RNA
      inhibited G1-phase progression and increased G1-phase gene transcripts, while
      decreasing S-phase and G2/M-phase gene transcripts, indicating the cell cycle was
      interrupted at the G1/S transition. SEPW1 mRNA levels were maximal during G1
      phase, dropped after the G1/S transition and increased again after G2/M-phase.
      SEPW1-underexpressing prostate cells had increased mRNA for BCL2, which can
      induce a G1 arrest, and decreased mRNA for RBBP8 and KPNA2, which modulate the
      Rb/p53 checkpoint pathway. These results suggest that SEPW1 and the G1/S
      transition are physiological targets of Se in breast and prostate epithelial
      cells.

PMID- 19387568
TI  - Semi-continuous cultivation of Haematococcus pluvialis for commercial production.
AB  - The objectives of the present study on the growth of Haematococcus pluvialis were
      to indicate the effects of a long-term semi-continuous cultivation,
      sterilization, carbon dioxide, and different culture media by using artesian well
      water. This investigation was an enterprise in order to commercialize the
      production economically. When the effect of CO(2) was investigated in basal
      culture medium, the influence of sterilization was also researched in Rudic's
      culture medium in vertical panel-type photobioreactors for 31 days of semi
      continuous cultivation. The maximum cell concentration of 10.55 x 10(5) cells ml(
      1), which corresponds to the growth rate of 0.271 day(-1) with the areal
      productivity of 3.531 g m(-2) day(-1), was found in non-sterilized RM medium on
      the 24th day of the third run of semi-continuous cultivation at a renewal rate of
      50% in a vertical panel-type photobioreactor.

PMID- 19387569
TI  - Influence of infrasound exposure on the whole L-type calcium currents in rat
      ventricular myocytes.
AB  - This study was designed to examine the effect of infrasound exposure (5 Hz at 130
      dB) on whole-cell L-type Ca2+ currents (WLCC) in rat ventricular myocytes and the
      underlying mechanism(s) involved. Thirty-two adult Sprague-Dawley rats were
      randomly assigned to infrasound exposure and control groups. [Ca2+](i), WLCC,
      mRNA expression of the a(1c) subunit of L-type Ca2+ channels (LCC), and SERCA2
      protein were examined on day 1, 7, and 14 after initiation of infrasound
      exposure. Fluo-3/AM fluorescence and the laser scanning confocal microscope
      techniques were used to measure [Ca2+](i) in freshly isolated ventricular
      myocytes. The Ca2+ fluorescence intensity (FI), denoting [Ca2+](i) in
      cardiomyocytes, was significantly elevated in a time-dependent manner in the
      exposure groups. There was a significant increase in WLCC in the 1-day group and
      a further significant increase in the 7- and 14-day groups. LCC mRNA expression
      measured by RT-PCR revealed a significant rise in the 1-day group and a
      significant additional rise in the 7- and 14-day groups compared with control
      group. SERCA2 expression was significantly upregulated in the 1-day group
      followed by an overt decrease in the 7- and 14-day groups. Prolonged exposure of
      infrasound altered WLCC in rat cardiomyocytes by shifting the steady-state
      inactivation curves to the right (more depolarized direction) without altering
      the slope and biophysical properties of I (Ca,L). Taken together, our data
      suggest that changes in [Ca2+](I) levels as well as expression of LCC and SERCA2
      may contribute to the infrasound exposure-elicited cardiac response.

PMID- 19387571
TI  - Disulfide and multisulfide antitumor agents and their modes of action.
AB  - A variety of natural products that contain disulfide or multisulfide bonds were
      found to display potent biological activities, including antitumor activities. At
      the center of these biological activities are disulfide or multisulfide moieties.
      The importance of disulfide or multisulfide groups in the areas of chemistry,
      biology, and pharmacology has been well recognized. Among these agents,
      especially noteworthy are mitomycin disulfides, leinamycin, thiarubrines,
      varacins, calicheamicins, and esperamicins. Their general features, including
      their biological profiles, peculiar structures, and related chemistries, were
      summarized and more importantly, their working mechanisms were elucidated in
      detail in this review. Mechanistic studies of these compounds have provided
      evidence of the key role of disulfide or multisulfide groups. In general, the
      cleavage of disulfide or multisulfide bonds produces thiol (or thiolate), which
      triggers an activation cascade leading to the generation of highly reactive
      electrophile(s) or cytotoxic species that may cause DNA strand scission. The main
      concerns with the mode of action are the reactivity and stability of disulfide
      and multisulfide bonds, their cleavage conditions, and the generation of toxic
      species. A range of studies for each agent was executed to gather important
      information on their activation, and the obtained information was gradually
      integrated to give some clues to the agents' working mechanisms. Such information
      may be further used to generate biomechanistically designed and more potent
      derivatives.

PMID- 19387572
TI  - Pharmacophore-based 3D-QSAR of HIF-1 inhibitors.
AB  - (Aryloxyamino)benzoic acids and nicotinic/isonicotinic acids represent an
      important new class of small molecules that inhibit the activation of hypoxia
      inducible factor (HIF)-1. In order to understand the factors affecting inhibitory
      potency of HIF-1 inhibitors, 3 dimensional-quantitative structure activity
      relationship (3D-QSAR) studies were performed. Since no receptor structure are
      available, the pharmacophore-based alignment was used for comparative molecular
      field analysis (CoMFA) and comparative molecular similarity indices analysis
      (CoMSIA). The CoMFA and CoMSIA models gave reasonable statistics (CoMFA: q(2) =
      0.564, r(2)=0.945; CoMSIA: q(2) = 0.575, r(2)=0.929). Both CoMFA and CoMSIA
      results indicate that the steric interaction is a major factor, while CoMSIA
      suggests importance of hydrogen bonding. These findings about steric and H
      bonding effects can be useful to design new inhibitors.

PMID- 19387573
TI  - A new Erythrinan alkaloid from the seed of Erythrina addisoniae.
AB  - Phytochemical study on the EtOAc extract of the seed of Erythrina addisoniae
      (Leguminosae) resulted in the isolation of a new erythrinan alkaloid, erysovine-N
      oxide (1), along with eight known alkaloids, erysosalvinone (2), erysodine (3),
      1H-indole-3-propanamide (4), glucoerysodine (5), erysotrine (6), erysovine (7),
      erythraline (8) and erysopine (9). Their chemical structures were identified on
      the basis of physicochemical and spectroscopic analyses.

PMID- 19387574
TI  - Lignan constituents from Chloranthus japonicus Sieb.
AB  - A new coumarinolignan glucoside named yinxiancaoside C, along with five known
      benzofuran lignans, have been isolated from the whole plant of Chloranthus
      japonicus Sieb. The structures of compounds 1-6 were elucidated by chemical and
      spectroscopic methods including 1D-NMR, 2D-NMR, ESI-MS and HR-ESI-MS. Five known
      benzofuran lignans were firstly discovered in the Chloranthaceae. In addition,
      the cytotoxic activity of the isolated compounds against human hepatoma (Hepg-2),
      ovarian carcinoma (OV420), and breast cancer (MCF-7) cells was investigated by
      MTT method.

PMID- 19387575
TI  - Quantitative analysis of nargenicin in Nocardia sp. CS682 culture by high
      performance liquid chromatography.
AB  - A simple and sensitive HPLC method was developed for the quantitative analysis of
      nargenicin in the culture broth of Nocardia sp. CS682, isolated from Korean soil.
      Nargenicin, an unusual macrolide antibiotic with potent anti-MRSA (methicilin
      resistant Staphylococcus aureus) activity, was extracted from the culture broth
      with ethylacetate and then analyzed by HPLC using solvent A (0.5 M dipotassium
      phosphate pH 2.5-water: acetonitrile = 80:20, v/v) and solvent B (100%
      acetonitrile), at 215 nm. The calibration curve of nargenicin was linear with
      correlation coefficient greater than 0.99. This method provides precise analysis
      of the nargenicin amount present in the cell free culture medium, and may be
      applicable to analyze other bacterial cultures containing similar compounds.

PMID- 19387576
TI  - Hydroxyl radical scavenging activities of isoquinoline alkaloids isolated from
      Coptis chinensis.
AB  - The hydroxyl radical (*OH) scavenging and ferrous ion chelating activities of
      four isoquinoline alkaloids isolated from Coptis chinensis Franch were studied
      for the identification of their structural characteristics to scavenge *OH. The
      *OH was generated via Fe(II)-catalazed Fenton reaction in this study and the
      reliable measurement of *OH scavenging activities of isoquinoline alkaloids were
      achieved using electron spin resonance (ESR) spectrometry method. At the 1 mM
      concentration, berberrubine (85%) showed the strongest *OH scavenging activity
      and the next were in the decreasing order of coptisine (79%), berberine (23%),
      and palmatine (22%). The ferrous ion chelating effects of the alkaloids showed
      similar pattern with their *OH scavenging effects. These results suggest that *OH
      scavenging effects of the alkaloids were closely related to their ferrous ion
      chelating activities. In addition, metal chelating functional groups such as
      hydroxy group at C-9 and methylenedioxy group at C-9 and C-10 were thought to
      contribute to the *OH scavenging activities of the isoquinoline alkaloids.

PMID- 19387577
TI  - Effect of Korean red ginseng extract in a steroid-induced polycystic ovary murine
      model.
AB  - Experimental induction of polycystic ovary (PCO) in rodent resembling some
      aspects of human PCO syndrome was produced using the long-acting compound
      estradiol valerate (EV). Our previous study on the role of Korean red ginseng
      total saponins in a steroid-induced PCO rat model demonstrated that electro
      acupuncture modulates nerve growth factor (NGF) concentration in the ovaries. In
      fact, the involvement of a neurogenic component in the pathology of PCO-related
      ovarian dysfunction is preceded by an increase in sympathetic outflow to the
      ovaries. In the present study, we tested the hypothesis that Korean red ginseng
      extract (KRGE) administration modulates sympathetic nerve activity in PCO-induced
      rats. This was done by analyzing NGF protein and NGF mRNA expression involved in
      the pathophysiological process underlying steroid-induced PCO. EV injection
      resulted in significantly higher ovarian NGF protein and NGF mRNA expression in
      PCO-induced rats compared to control rats, and PCO ovaries were counteracted by
      KRGE administration with significantly lower expression of NGF protein and NGF
      mRNA compared to EV treated ovaries. These results indicate that EV modulates the
      neurotrophic state of the ovaries, which may be a component of the pathological
      process by which EV induces cyst formation and anovulation in rodents.

PMID- 19387578
TI  - Beneficial effects of the combination of amlodipine and losartan for lowering
      blood pressure in spontaneously hypertensive rats.
AB  - A combination of antihypertensive agents can better control blood pressure and
      reduce the number and severity of side effects than a monotherapy. Since both
      CCBs (calcium channel blockers) and ARBs (angiotensin II receptor type-1
      blockers) are current and effective antihypertensive drugs, this study assessed
      the synergistic antihypertensive effects as well as the optimal combination ratio
      of these two drugs. Amlodipine (3 mg/kg) or losartan (30 mg/kg) alone or a
      combination of each drug at a ratio 1:10 and 1:20 was administered orally to
      spontaneously hypertensive rats (SHR). A four-week treatment of either 3 mg/kg
      amlodipine or 30 mg/kg losartan alone decreased the systolic blood pressure
      (SBP). However, their combination significantly lowered the SBP from the 3(rd)
      week, and there was a positive correlation between this reduction in blood
      pressure and the improvement in arterial endothelium-dependent relaxation. In
      addition, the combination therapy (1:20) decreased both the cardiac mass and left
      ventricular weight to a greater extent than with either amlodipine or losartan
      alone. The collagen content in the cardiac tissue was also significantly lower
      after the 4-week combination therapy (1:10). These results suggest that the
      combined use of amlodipine and losartan might be more effective in treating
      hypertension than a monotherapy.

PMID- 19387579
TI  - Preparation of sustained release microparticles with improved initial release
      property.
AB  - The objective of this study was to investigate the potential of various
      formulation strategies to achieve sustained release of the peptide, from
      injectable poly(D,L-lactide-co-glycolide) (PLGA) and d-alpha-tocopheryl
      polyethylene glycol 1000 succinate (TPGS) microparticles. The microparticles were
      prepared by a solvent evaporation method. Peptide loaded PLGA microparticles
      exhibited a pronounced initial burst release (22.3% in 1 day) and lag phase in
      phosphate buffer of pH 7.0. In contrast, blending of 5.0% TPGS (8.6% release in 1
      day) or 10.0% TPGS (5.5% release in 1 day) in PLGA microparticles reduced initial
      burst release and the lag-phase time. Incorporation of TPGS in PLGA
      microparticles further increased drug release, attributable to improved drug
      encapsulation, increased particle size, and exempt of pores. PLGA+ 10.0% TPGS
      composite microparticles exhibited the most desirable drug release among all the
      formulations tested, and demonstrated triphasic release after minimal initial
      burst.

PMID- 19387580
TI  - Inhibitory effects of arbutin on melanin biosynthesis of alpha-melanocyte
      stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig
      skin tissues.
AB  - Arbutin has been used as a whitening agent in cosmetic products. Melanin, the
      major pigment that gives color to skin, may be over-produced with sun exposure or
      in conditions such as melasma or hyperpigmentary diseases. Tyrosinase is a key
      enzyme that catalyzes melanin synthesis in melanocytes; therefore, inhibitors of
      the tyrosinase enzyme could be used for cosmetic skin whitening. A recent study
      has reported that arbutin decreases melanin biosynthesis through the inhibition
      of tyrosinase activity. However, this inhibitory mechanism of arbutin was not
      sufficiently demonstrated in skin tissue models. We found that arbutin both
      inhibits melanin production in B16 cells induced with alpha-MSH and decreases
      tyrosinase activity in a cell-free system. Furthermore, the hyperpigmentation
      effects of alpha-MSH were abrogated by the addition of arbutin to brownish guinea
      pig and human skin tissues. These results suggest that arbutin may be a useful
      agent for skin whitening.

PMID- 19387581
TI  - Hemin inhibits hypertensive rat vascular smooth muscle cell proliferation through
      regulation of cyclin D and p21.
AB  - We tested the hypothesis that HO-1 (heme oxygenase-1) activity varied between
      vascular smooth muscle cells (VSMC) in spontaneously hypertensive (SHR) and
      normotensive Wistar-Kyoto (WKY) rats. HO-1 levels were measured under baseline
      and hemin-stimulated conditions and cell proliferation was monitored. Basal HO-1
      levels in untreated cells were lower in SHR compared to WKY rats. Treatment with
      hemin increased HO-1 mRNA and protein levels in the cells obtained from WKY rats
      compared to that of SHR rats. However, hemin-treatment showed a greater
      inhibitory effect on VSMC proliferation in SHR rats than in WKY rats. Tin
      protoporphyrin IX (SnPPIX) showed a greater reversal of the anti-proliferative
      effect of hemin on cells from SHR rats than WKY. Similarly, VSMC proliferation
      from SHR was significantly inhibited in VSMC transfected with the HO-1 gene.
      These inhibitory effects were associated with cell cycle arrest in the G1 phase.
      The level of cyclin D, and cyclin dependent kinase inhibitor p21 was higher in
      SHR cells progressing through the G1 phase. Treatment of the cells with hemin
      down-regulated the expression of cyclin D and up-regulated that of p21. These
      results indicate that hemin, an HO-1 inducer, may play a more critical role in
      VSMC proliferation in SHR than WKY.

PMID- 19387582
TI  - Serologic response to human papillomavirus type 16 virus-like particles in Korean
      women with cervical precancerous and cancerous lesions.
AB  - The aim of the study was to investigate the seroprevalence to HPV type 16 in
      Korean women with precancerous and cancerous lesions of the uterine cervix. The
      cases were 173 Korean women of whom 130 had high-grade cervical intraepithelial
      neoplasias (CIN), 43 cervical carcinomas and the control group was 106 women
      showing normal cervical cytology. Serologic assays were performed using HPV-16
      VLPs as antigen in an ELISA. Specific antibodies against HPV-16 VLP were detected
      in 59.2% (77/130) of the patients with high-grade CIN, in 67.4% (29/43) of the
      patients with cervical cancer and in 20.8% (22/106) of control subjects. No
      difference of serologic response was found between high-grade CIN and cancer. HPV
      16 seropositivity showed the significant association with patients' age and
      preoperative HPV DNA infection. Recurrence of high-grade CIN was not affected by
      the VLP-16 seropositivity. Recurrence of carcinoma showed the borderline
      association with HPV-16 seropositivity (P=0.06). The association between the
      cancer recurrence and seropositivity was not found in the logistic regression
      analysis. Two patients dying of cancer during the follow-up period were both
      seronegative (P=0.01). In conclusion, serologic testing for HPV-16 VLP antibody
      provides a disease indicator of cervical lesions and potential prognostic
      parameter of cervical carcinoma.

PMID- 19387583
TI  - Development of novel mucoadhesive pellets of metformin hydrochloride.
AB  - Mucoadhesive polymer-coated pellets containing metformin hydrochloride were
      prepared by the powder-layering technique using a centrifugal fluidizing (CF)
      granulator. Four high-viscosity polymers were applied to make the pellets: 1)
      hydroxymethylcellulose (HPMC), 2) sodium alginate (Na-Alg), 3) HPMC/Carbopol, and
      4) sodium carboxylmethylcellulose (Na-CMC). The physical crushing test,
      mucoadhesive test, zeta-potential test, in vitro release study and observation of
      gastroretention state of the dosage form were performed to investigate the
      pellets. The strong adhesive interaction between the Na-CMC-coated pellets and
      the mucin disc was obtained by mucoadhesive test. Na-Alg was most effective among
      the polymers used in changing the value of zeta potential of the mucin solution
      by the interaction between a polymer and a mucin particle. Results from drug
      dissolution study showed that over 95% of the drug from all the four pellets was
      released before 2 h, while Na-CMC- and Na-Alg-coated pellets showed a moderate
      sustained-release in SGF (simulated gastric fluid) and SIF (simulated intestine
      fluid), respectively. In conclusion, Na-CMC and Na-Alg seem to be promising
      candidates for mucoadhesive formulation and further studies to improve the
      sustained-release property are underway for achieving the ultimate goal of once-a
      day formulation of metformin hydrochloride.

PMID- 19387584
TI  - Effects of schisandrin on transcriptional factors in lipopolysaccharide
      pretreated macrophages.
AB  - Schisandrin is the main active ingredient isolated from Schisandra chinensis
      Baill. Recent studies have demonstrated that schisandrin exhibits anti
      inflammatory effects in vivo and in vitro. In this study, we examined whether the
      order of lipopolysaccharide (LPS) treatment affects the mechanism of schisandrin
      anti-inflammatory activity. We found that the antiinflammatory mechanisms are not
      the same depending on whether macrophages were treated with schisandrin before or
      after LPS. The main difference is that inhibitor kappaBalpha (IkappaBalpha)
      degradation was not inhibited when macrophages were pretreated by LPS before
      schisandrin and was weakly inhibited when macrophages were pretreated by
      schisandrin before LPS.

PMID- 19387585
TI  - Effect of psoralen on the cloned Kv3.1 currents.
AB  - The psoralen, a furocoumarin derivative, on the cloned neuronal rat Kv3.1
      channels stably expressed in Chinese hamster ovary cells was investigated using
      the whole-cell patch-clamp technique. Psoralen reduced Kv3.1 whole-cell currents
      in a reversible concentration-dependent manner, with an IC50 value and a Hill
      coefficient of 2.3 +/- 0.03 microM and 0.9 +/- 0.08, respectively. Psoralen
      accelerated the decay rate of inactivation of Kv3.1 currents without modifying
      the kinetics of current activation. The psoralen-induced inhibition of Kv3.1
      channels was voltage-dependent, with a steep increase over the voltage range of
      channel opening. However, the inhibition exhibited voltage independence over the
      voltage range in which channels are fully activated. Psoralen slowed the
      deactivation time course, resulting in a tail crossover phenomenon when the tail
      currents, recorded in the presence and absence of psoralen, were superimposed.
      Inhibition of Kv3.1 by psoralen was use-dependent at a frequency of 1 Hz. The
      present results suggest that psoralen acts on Kv3.1 currents as an open-channel
      blocker.

PMID- 19387586
TI  - Inhibition of intestinal motility by the putative BK(Ca) channel opener LDD175.
AB  - LDD175 (4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic
      acid) is a benzofuroindole compound characterized previously as a potent opener
      of the large conductance calcium activated (BK(Ca)) channels. Activators of the
      BK(Ca) channels are potential therapies for smooth muscle hyperactivity
      disorders. The present study investigates the influence of LDD175 on the
      mechanical activity of the ileum smooth muscle. LDD175 inhibited spontaneous
      contractions of the ileum in a concentration-dependent manner (pEC(50)=5.9 +/-
      0.1) (E (max)=96 +/- 1.0% at 100 muM, n=3). It also remarkably inhibited
      contractions due to acetylcholine (ACh) (pEC(50)=5.3 +/- 0.1)(E (max)=97.7 +/-
      2.3%, n=6) and electrical field stimulation (EFS) (pEC(50)=5.5 +/- 0.1) (E
      (max)=83.3 +/- 6.0%, n=6). In strips precontracted by 20 mM KCl, LDD175
      significantly reduced the contractions yielding a pEC(50) of 6.1 +/- 0.1 and E
      (max) of 96.6 +/- 0.9%, (n=6). In 60 mM KCl, a concentration-dependent inhibition
      was observed with respective pEC(50) and E (max) values of 4.1 +/- 0.1 and 50.8
      +/- 5.0% (n=3). BK(Ca) channel blockers iberiotoxin (IbTX) and tetraethylammonium
      chloride (TEA, 1 mM) attenuated the relaxative effect of LDD175 but not barium
      chloride (BaCl(2)), and glibenclamide (K(IR) and K(ATP) channel blockers,
      respectively). These data demonstrate the antispasmodic activity of LDD175
      attributable to the potentiation of the BK(Ca) channels.

PMID- 19387587
TI  - A novel in vitro ischemia/reperfusion injury model.
AB  - The reperfusion of blood flow occurred in a number of conditions such as stroke
      and organ transplantation immensely augments tissue injury and causes more severe
      damage than prolonged ischemia. In the present study, we designed a novel double
      layer parallel-plate flow chamber (PPFC) to develop an in vitro
      ischemia/reperfusion (I/R) injury model and examined the effects of I/R on
      inflammatory responses in human microvascular endothelial cells (HMEC-1). The
      expression of pro-inflammatory mediators, such as interleukin-6 (IL-6), monocyte
      chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), E
      selectin, and vascular cell adhesion molecule-1 (VCAM-1) in HMEC-1 was measured
      by quantitative real-time RT-PCR. The cells were also pre-treated with
      antioxidant pyrrolidine dithiocarbamate (PDTC) to verify involvement of an
      oxidative mechanism in I/R injury in vitro. The morphological changes and
      attenuated expression of pro-inflammatory mediators were observed in HMCE-1
      exposed to the physiological flow. In contrast, I/R markedly and significantly up
      regulated expression of pro-inflammatory mediators in HMEC-1. Additionally,
      pretreatment with PDTC significantly reduced I/R-mediated overexpression of pro
      inflammatory mediators. The data from the present study provide evidence
      demonstrating that our newly designed PPFC can be utilized as an effective in
      vitro cell culture model system to develop new drugs specifically targeting
      against ischemia/reperfusion (I/R) injury.

PMID- 19387588
TI  - Antitumor actions of imidazolyl-(4-oxoquinazolin-3(4H)-yl)-acetamides against
      Ehrlich Ascites Carcinoma.
AB  - Breast cancer is the second most common type of cancer after lung cancer and the
      fifth most common cause of cancer death. Several structural classes of compounds
      were discovered against tumor, but many of the existing antitumor agents exhibit
      severe side effects. Hence there is a need to identify a novel chemical entity
      having a broad range of therapeutic activity with fewer side effects. In this
      direction, several imidazolyl-(4-oxoquinazolin-3(4H)-yl)-acetamides 1-4(a-d) were
      screened for their antitumor activity against Ehrlich Ascites Carcinoma (EAC)
      using in-vitro and in-vivo models. Compounds 4b, 4d, and 3a showed highly
      significant antitumor activity against EAC in comparison with vincristine as
      standard.

PMID- 19387589
TI  - Monoclonal antibody production and immunochemical detection of polyether
      antibiotics.
AB  - Polyether antibiotics such as monensin and salinomycin have been primarily used
      as coccidiostat and growth promoter. Since residues of these antibiotic in food
      may pose a health risk for sensitive individuals, their use should be carefully
      monitored. An immunochemical method was developed for the determination of
      polyether antibiotic using monoclonal antibody (Mab) produced by immunized mice.
      Conjugates of monensin, salinomycin and laidlomycin were prepared with bovine
      serum albumin (BSA), keyhole limpet haemocyanine (KLH) and ovalbumin (OVA) by
      mixed anhydride method and then used as immunogene to produce Mab. Eight
      hybridoma cell lines were isolated that produced Mabs that competed with
      polyether antibiotic-protein conjugates in BALB/c-SP2/0 fusion system. Two
      hybridoma with higher sensitivity, designated as 4G11F and 1C8F1F, were cultured
      for mass production and then purified from ascites fluid. Antibiotic-protein
      conjugates were quantitavely analyzed by using the purified Mabs through a
      competitive enzyme-linked immunosorbent assay (ELISA).

PMID- 19387590
TI  - Mistletoe lectin modulates intestinal epithelial cell-derived cytokines and B
      cell IgA secretion.
AB  - A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. var.
      coloratum agglutinin, VCA), which is known for its anti-cancer activity, was
      isolated from Korean mistletoe. In this study, IEC-6 rat intestinal epithelial
      cells and IM-9 human B-cells were cultured to determine the effect of VCA on
      cytokine and immunoglobulin (Ig) secretion. In lipopolysaccharide (LPS)
      stimulated IEC-6 cells, VCA significantly shifted the interleukin (IL)-2, IL-5,
      IL-6, and tumor necrosis factor-alpha (TNF-alpha) secretion toward a more
      immunostimulatory response. Since intestinal epithelial cell-derived secretions
      may be capable of affecting local B cell Ig production in a variety of ways, we
      mimicked this condition by deriving a 2-day culture supernatant from IEC-6 cell
      line which was treated VCA in the presence or absence of LPS, and adding these
      supernatants to cultures of IM-9 human B cells. As a result, IgA secretion was
      significantly enhanced at in the presence of VCA at 10(-8)-10(-4) microg/mL. This
      study suggests that cytokines derived from IEC by VCA may create an environment
      which may contribute to the enhancement of IgA secretion seen in mucosal tissues.
      Overall, the induction of cytokines in intestinal epithelial cells, and IgA in B
      cells by Korean mistletoe lectin could indicate an enhanced immunosurveillance to
      prevent intestinal infections or other intestinal pathologies.

PMID- 19387591
TI  - Two enone fatty acids isolated from Gracilaria verrucosa suppress the production
      of inflammatory mediators by down-regulating NF-kappaB and STAT1 activity in
      lipopolysaccharide-stimulated RAW 264.7 cells.
AB  - Gracilaria verrucosa is a common marine red alga that has anti-oxidant and anti
      cancer properties. Recently, we reported that anti-inflammatory constituents of
      G. verrucosa operate through an unknown mechanism. For this reason, we isolated
      two enone fatty acids from G. verrucosa and investigated their molecular
      mechanism in LPS-stimulated RAW264.7 cells. We found that the two compounds
      inhibited the production of inflammatory markers (nitric oxide, TNF-alpha, and IL
      6) in a dose-dependent manner. We next studied the effects of G. verrucosa
      compounds on LPS-induced signaling pathways. The two compounds suppressed NF
      kappaB reporter activity by interfering with nuclear translocation of NF-kappaB
      and suppressed JAK/STAT (p-STAT1) signaling. These results suggest that G.
      verrucosa inhibits the production of inflammatory mediators (NO, TNF-alpha, and
      IL-6) by suppressing the activation of NF-kappaB and the phosphorylation of
      STAT1.

PMID- 19387592
TI  - [Expanding papillomatous nodule on forearm with acute lymphangitis. Case of
      diagnosis].
AB  - Ecthyma contagiosum (orf) is a dermatosis commonly seen in those in contact with
      sheep. It is caused by Parapoxvirus ovis (orf virus), an oval epitheliotropic DNA
      parapox virus. The skin disease develops in stages starting as a macule or
      papule, becoming nodular, and then regressing. Diagnosis is based on history and
      histology, as well as identifying the virus through cell culture or specified
      polymerase chain reaction (PCR). The treatment of this self-limited disease is
      usually symptomatic.

PMID- 19387593
TI  - [Symptomatic cardiac metastasis. Isolated visceral manifestation of a cutaneous
      malignant melanoma].
AB  - Symptomatic cardiac melanoma metastases are very rare. A 76-year-old woman was
      admitted because of dyspnea and intrathoracic pain 8 years after surgery of a
      superficial spreading melanoma and 4 years after resection of in-transit
      metastases. MRI and echocardiography disclosed an intracavitary right atrial
      mass. Histologically a cardiac melanoma metastasis was found. Unspecific cardiac
      symptoms in a patient with elevated risk for distant metastases of melanoma
      should be further investigated to discover cardiac metastasis early.

PMID- 19387594
TI  - [Sexually transmitted infections relevant in andrologic diagnostics].
AB  - Affects on male fertility are associated with many sexually transmitted diseases.
      Genital tract infections play a major role in this context. The evidence for an
      impact on fertility differs for the pathogens; however early treatment may be
      very important. This requires fast and precise clinical diagnostics. Further,
      sexually transmitted infections may have major relevance in andrologic
      diagnostics because of the risk of transmission to the mother or fetus.
      Particularly for the increasingly relevant HIV and hepatitis infections, current
      guidelines are available for use in diagnostics and assisted reproduction
      techniques.

PMID- 19387595
TI  - [Vestibular compensation : basic principles and clinical significance].
AB  - The vestibular system has the ability to repair deficits due to functional
      lesions, which is known as vestibular compensation. For successful function the
      performance of different receptors is less important than the bilateral balance
      of neuronal activity between the vestibular nuclei complexes. In this review
      based on data from animal experiments and clinical observations, the mechanisms
      of vestibular compensation, its time course and its clinical significance are
      described. Most of the clinical features can be explained by neuronal operations
      known from animal experiments. It must be emphasized that vestibular compensation
      is not a static phenomenon but a fluctuating process which can be influenced by
      therapeutic procedures. Vestibular compensation for static phenomena can be
      almost completely carried out, but for dynamic features only incompletely. These
      factors should be taken in account for diagnosis, therapy and assessment of
      vestibular disturbances.

PMID- 19387596
TI  - [Radiotherapy, chemotherapy and target therapy for treatment of head and neck
      cancer : new developments].
AB  - Approximately 60% of patients initially treated for squamous cell cancer of the
      upper gastrointestinal tract suffer from advanced tumor disease (UICC stages III
      and IV). Multimodal strategies lead to overall survival rates of up to 50%.
      Recent studies show indications that the risk of distant metastases after
      induction chemotherapy (CT) is less than after primary radiotherapy (RT) or
      radiochemotherapy (RCT). Hyperfractionation or accelerated radiation with
      concomitant boost shows superior results compared to classic RT. Intensity
      modulated radiotherapy (IMRT) is a new method for better adjusted dose
      distribution. Targeted therapy with specific antibodies against biological
      targets, such as epidermal growth factor receptor (EGFR), showed superiority over
      RT but the comparison to classic RCT is still pending. Targeted therapy against
      vascular endothelial growth factor (VEGR) showed antiangiogenetic effects on
      tumors. In cases of non-resectability or distant metastases, palliative CT and
      target therapy are recommended. Reirradiation or IMRT offer increased
      locoregional tumor control at the expense of higher toxicity. Overall, advances
      in research on tumor biology offer increasingly more prognostic factors and
      markers for customized individual targeted therapy and CT.

PMID- 19387597
TI  - [Immunocytochemical detection of caspase 3 in various diseases of human nasal
      mucosa].
AB  - BACKGROUND: Inflammatory processes play a central role in the pathogenesis of
      chronic rhinosinusitis (CRS), however, the impact of apoptosis in CRS in unclear.
      The aim of this study was a comparison of caspase 3 activity, a key enzyme in the
      apoptosis cascade, in samples of nasal tissue from patients with different types
      of rhinosinusitis. MATERIAL AND METHODS: Immunohistochemical analyses were
      carried out to detect caspase 3 in samples of nasal tissue from patients with CRS
      and nasal polyps (NP), allergic rhinitis (AR), rhinitis medicamentosa (RM) and
      atrophic rhinitis. RESULTS: Evidence of increased apoptosis was found in the
      epithelium, submucosal glands and blood vessels in NP samples. Samples of RM
      showed strong caspase 3 activity in the endothelial cells and the lamina
      muscularis of blood vessels. In atrophic rhinitis the epithelium and
      subepithelial glands showed increased caspase 3 activity. In samples of patients
      with allergic rhinitis caspase 3 activity could not be detected. CONCLUSIONS:
      Activated apoptosis seems to play an important role in the pathogenesis of
      different types of rhinosinusitis. Further investigations on the induction of
      caspase 3 are necessary for the development of new therapeutic strategies to
      influence the regulation of apoptosis.

PMID- 19387598
TI  - [Use of the internet for health information by ENT patients].
AB  - INTRODUCTION: The internet is becoming increasingly more important as a source of
      information for patients, so that nowadays internet-based information must be
      more frequently considered in the dialogue with patients. MATERIAL AND METHODS:
      This study is based on an analysis of ENT patients' habits in acquiring
      information from the internet. The data were collected by a questionnaire for in
      patients over a period of 9 months during 2006 and 2007. A total of 503 patients
      with different family backgrounds were interviewed and the answers analyzed with
      respect to the illness, age, gender, education and information acquisition from
      the internet. RESULTS: The younger generation was found to use the internet in
      general more than older patients and there were no differences between males and
      females. Middle aged patients in particular used the internet for answering
      questions on health. Patients with complex elective surgery used the internet
      more often than patients undergoing simple elective surgery and patients with
      tumors and private patients used the internet more often than those with social
      health insurance. Among the questioned patients it was noticeable that a high
      proportion of those using internet to obtain information were well educated.
      DISCUSSION: Despite the high quality of information available for ENT patients on
      the internet, information obtained from the treating physician is still preferred
      by many patients. Due to demographic changes an increased use of the internet for
      patient information is to be expected in the future. The correlation found in
      this study between education, insurance status and the use of the internet might
      play a role in a target group oriented improvement of information supply.

PMID- 19387599
TI  - [Space-occupying lesion of the thyroid cartilage].
AB  - A 46-year-old patient had had a slowly growing progressive but painless
      prelaryngeal space-occupying lesion for approximately 1 year. In addition there
      was also a longstanding hyperuricemia with gout tophi on the metatarsal basal
      joints 1-5 of both hands. The extirpated tumor proved to be a gout tophus by
      histological examination. Although this is a rare occurrence it should be
      considered as the possible cause of a tumor if there is a corresponding case
      history.

PMID- 19387600
TI  - [Liver transplantation: indications and results].
AB  - After around 64,000 transplantations in Europe since 1988 liver transplantation
      has emerged as a standard treatment option for otherwise incurable chronic liver
      diseases. Cirrhosis of different etiologies represents the most frequent
      transplant indication. Overall survival in this group amounts to 72% after 5
      years, and 62% after 10 years. In Germany, the main indications include alcoholic
      liver cirrhosis, tumors with increasing numbers in recent years, as well as viral
      diseases leading to cirrhosis. Since December 2006 the priority for liver
      transplantation is determined by the model for end stage liver disease (MELD) and
      not by the length of waiting time. MELD is a statistical model based on serum
      creatinine, serum bilirubin and coagulation, which describes the probability of 3
      month mortality of a potential transplant candidate. Not all liver diseases are
      adequately represented by MELD necessitating the additional use of a defined
      number of standard exceptions that have been last updated in 2008. As a
      consequence of these developments indications, selection of recipients and the
      management of the waiting list have seen profound change.

PMID- 19387601
TI  - Treatment of diabetes by transplantation of drug-inducible insulin-producing gut
      cells.
AB  - Most patients with type 1 diabetes rely on multiple daily insulin injections to
      maintain blood glucose control. However, insulin injections carry the risk of
      inducing hypoglycemia and do not eliminate diabetic complications. We sought to
      develop and evaluate a regulatable cell-based system for delivery of insulin to
      treat diabetes. We generated two intestinal cell lines in which human insulin
      expression is controlled by mifepristone. Insulin mRNA expression was dependent
      on the mifepristone dose and incubation time and cells displayed insulin and C
      peptide immunoreactivity and glucose-induced insulin release following
      mifepristone treatment. Cell transplantation followed by mifepristone
      administration reversed streptozotocin (STZ)-induced diabetes in mice, and this
      effect was dependent on the mifepristone dose delivered. These data support the
      notion that engineering regulatable insulin expression within a cell already
      equipped for regulated secretion may be efficacious for the treatment of insulin
      dependent diabetes.

PMID- 19387602
TI  - [Unipolar depressive disorders].

PMID- 19387603
TI  - [Mechanical recanalization].
AB  - Although several studies and registries have focused on new interventional
      systems for the treatment of acute ischemic stroke, a standard procedure has not
      yet been established. The procedure itself is still controversially discussed but
      studies have shown that patients who were successfully treated with mechanical
      recanalization had a better clinical outcome.

PMID- 19387605
TI  - [How safe are gadolinium-based contrast media? Nominal ranges for usage?].

PMID- 19387604
TI  - [Carotid artery stenting for acute stroke].
AB  - For patients with acute ischemic stroke due to total occlusion of the internal
      carotid artery (ICA), an effective intervention to improve neurologic symptoms
      and clinical outcome has not yet been established. Some authors have reported
      successful revascularization for patients with acute stroke symptoms secondary to
      ICA occlusion only in isolated series and case reports. Emergency recanalization
      and carotid artery stent placement can improve neurologic outcome in selected
      patients with acute ischemic stroke and total occlusion of the ICA.

PMID- 19387607
TI  - [Stress urinary incontinence after radical cystectomy: neobladder construction
      and placement of the functional retrourethral sling].
AB  - Stress urinary incontinence (SUI) following radical cystectomy and orthotopic
      ileal neobladder construction represents a challenging problem. The incidence of
      incontinence following this surgery is reported to be 30-60% and is - despite a
      better understanding of the male (and female) pelvic anatomy - still regarded as
      an adverse outcome of this surgery.Therapeutic options have been limited up until
      now and include pharmacological agents, surgical treatment and pelvic floor
      training with only moderate amelioration of the symptoms and often unacceptable
      side effects. Nevertheless, urinary continence is probably the most important key
      to patient satisfaction. Here we introduce the perineal approach of the
      functional retrourethral mesh as a new and innovative sling suspension based on a
      non-obstructive procedure in a patient with urinary stress incontinence after
      ileal neobladder. The sling adjusts the changed anatomy after radical cystectomy
      returning it to the former preoperative position and thus continence can be
      achieved again. The approach of the sling in a patient with ileal neobladder is
      safe and the good result concerning continence is promising.

PMID- 19387608
TI  - [Practice marketing. Data analysis of a urological group practice].
AB  - The urological practice setting in Germany has changed tremendously over the last
      years. Group practices with two or more urologists working together are becoming
      more and more popular. At the same time, marketing has become essential even for
      urologists. To evaluate the patient flow to our group practice, we asked all new
      patients to fill out a questionnaire (n=2112). We also evaluated the efficacy of
      our recall system. The analysis showed that patients were 18-93 years old (mean
      57 years), 68% being male and 32% female. The largest age group consisted of 41
      50-year-olds. The most important reasons for choosing our practice were
      recommendations by general practitioners in 38%, recommendations by specialists
      in 11%, and recommendations by friends and relatives in 27%. Five percent of the
      patients chose the practice because of the Internet home page and 10% because of
      entries in various phone books. Three percent of the patients came because of
      newspaper articles about the practice owners, and <1% had attended patient
      presentations. The Internet was used mainly by 31-40-year-old patients. Our
      recall system showed an efficacy of 59%. In summary, a good reputation in the
      medical society as well as in the neighbourhood is still the best advertising for
      a urological practice. Phone books are increasingly becoming less important, and
      the Internet is increasingly attractive to the younger population. Recall systems
      can also be useful for urological practices.

PMID- 19387609
TI  - A new interspecific, Gossypium hirsutum x G. barbadense, RIL population: towards
      a unified consensus linkage map of tetraploid cotton.
AB  - We report the development of a new interspecific cotton recombinant inbred line
      (RIL) population of 140 lines deriving from an interspecific cross between
      Gossypium hirsutum (Gh) and G. barbadense (Gb), using the same two parents that
      have served for the construction of a BC(1) map and for the marker-assisted
      backcross selection program underway at CIRAD. Two marker systems,
      microsatellites and AFLPs, were used. An important feature of the RIL population
      was its marked segregation distortion with a genome-wide bias to Gh alleles
      (parental genome ratio is 71/29). The RIL map displays an excellent colinearity
      with the BC(1) map, although it is severely contracted in terms of map size.
      Existence of 255 loci in common (between 6 and 14 per chromosome) allowed the
      integration of the two data sets. A consensus BC(1)-RIL map based upon 215
      individuals (75 BC1 + 140 RIL) was built. It consisted of 1,745 loci, spanned
      3,637 cM, intermediate between the sizes of the two component maps, and
      constituted a solid framework to cross align cotton maps using common markers.
      The new RIL population will be further exploited for fiber property QTL mapping
      and eQTL mapping.

PMID- 19387610
TI  - Brain-derived neurotrophic factor is produced by skeletal muscle cells in
      response to contraction and enhances fat oxidation via activation of AMP
      activated protein kinase.
AB  - AIMS/HYPOTHESIS: Brain-derived neurotrophic factor (BDNF) is produced in skeletal
      muscle, but its functional significance is unknown. We aimed to determine the
      signalling processes and metabolic actions of BDNF. METHODS: We first examined
      whether exercise induced BDNF expression in humans. Next, C2C12 skeletal muscle
      cells were electrically stimulated to mimic contraction. L6 myotubes and isolated
      rat extensor digitorum longus muscles were treated with BDNF and phosphorylation
      of the proteins AMP-activated protein kinase (AMPK) (Thr(172)) and acetyl
      coenzyme A carboxylase beta (ACCbeta) (Ser(79)) were analysed, as was fatty acid
      oxidation (FAO). Finally, we electroporated a Bdnf vector into the tibialis
      cranialis muscle of mice. RESULTS: BDNF mRNA and protein expression were
      increased in human skeletal muscle after exercise, but muscle-derived BDNF
      appeared not to be released into the circulation. Bdnf mRNA and protein
      expression was increased in muscle cells that were electrically stimulated. BDNF
      increased phosphorylation of AMPK and ACCbeta and enhanced FAO both in vitro and
      ex vivo. The effect of BDNF on FAO was AMPK-dependent, since the increase in FAO
      was abrogated in cells infected with an AMPK dominant negative adenovirus or
      treated with Compound C, an inhibitor of AMPK. Electroporation of a Bdnf
      expression vector into the tibialis cranialis muscle resulted in increased BDNF
      protein production and tropomyosin-related kinase B (TrkB(Tyr706/707)) and
      extracellular signal-regulated protein kinase (p44/42 Thr(202)/Tyr(204))
      phosphorylation in these muscles. In addition, phosphorylation of ACCbeta was
      markedly elevated in the Bdnf electroporated muscles. CONCLUSIONS/INTERPRETATION:
      These data identify BDNF as a contraction-inducible protein in skeletal muscle
      that is capable of enhancing lipid oxidation in skeletal muscle via activation of
      AMPK.

PMID- 19387611
TI  - Relationship between glycated haemoglobin and microvascular complications: is
      there a natural cut-off point for the diagnosis of diabetes?
AB  - AIMS/HYPOTHESIS: This study was designed to determine whether the relationship of
      glycated haemoglobin to diabetic microvascular complications shows any natural
      thresholds that could be useful in diagnosing diabetes. METHODS: We examined a
      population-based sample of 3,190 Malay adults aged 40-80 years in Singapore. The
      microvascular outcomes of interest were: (1) any retinopathy, defined from fundus
      photographs; (2) mild retinopathy, defined as in (1); (3) moderate retinopathy,
      defined as in (1); (4) chronic kidney disease, defined from estimated glomerular
      filtration rate; (5) micro- or macroalbuminuria, defined from urinary albumin to
      creatinine ratio; and (6) peripheral neuropathy, defined from neurothesiometer or
      monofilament sensory testing. RESULTS: Increasing HbA(1c) was associated with all
      microvascular complications. The optimal cut-off points for detecting mild and
      moderate retinopathy were 6.6% (87.0% sensitivity, 77.1% specificity and area
      under the receiver operating characteristics [ROC] curve 0.899) and 7.0% (82.9%
      sensitivity, 82.3% specificity and area under ROC curve 0.904). The prevalences
      of mild and moderate retinopathy were <1% below the optimal cut-off points. For
      other complications, the association with HbA(1c) was linear without evidence of
      a distinct threshold. Although ROC analysis for these other complications also
      suggested optimal cut-off points between 6.6% and 7.0%, the sensitivity at these
      cut-off points was considerably lower than for mild and moderate retinopathy,
      ranging from 31.8% to 66.5%. CONCLUSIONS/INTERPRETATION: Higher levels of HbA(1c)
      were associated with microvascular complications. Our data support use of an
      HbA(1c) cut-off point of between 6.6 and 7.0% in diagnosing diabetes. Cut-off
      points in this range were best for the identification of individuals with mild
      and moderate retinopathy. Any retinopathy, chronic kidney disease, albuminuria
      and peripheral neuropathy are less well detected at these cut-off points.

PMID- 19387612
TI  - Translating TCF7L2: from gene to function.

PMID- 19387613
TI  - [Elastic stable intramedullary nailing of a lower leg fracture in a patient with
      chronic spinal cord injury. A therapeutic alternative].
AB  - Therapy of lower leg fractures in patients with chronic spinal cord injury is
      discussed controversially in the literature. Pros and cons are pointed out for
      both conservative and operative therapy. Getting out of his wheelchair a 59-year
      old patient with chronic spinal cord injury suffered a lower leg fracture.
      Minimally invasive elastic stable intramedullary nailing (ESIN) was performed to
      gain sufficient stability for physiotherapy. The follow-up yielded excellent
      clinical and radiological results. ESIN is an adequate therapeutic alternative
      for lower leg fractures in patients with chronic spinal cord injury.

PMID- 19387614
TI  - HTR2A A-1438G/T102C polymorphisms predict negative symptoms performance upon
      aripiprazole treatment in schizophrenic patients.
AB  - RATIONALE: Aripiprazole acts as a partial agonist at dopamine D2 and D3 and
      serotonin 1A receptors and as an antagonist at serotonin 2A receptors (HTR2A).
      Since aripiprazole acts as an antagonist at HTR2A, genetic variants of HTR2A may
      be important in explaining variability in response to aripiprazole. OBJECTIVES:
      This study investigated whether the efficacy of aripiprazole can be predicted by
      functional HTR2A A-1438G/T102C polymorphisms (rs63311/rs6313) as modified by
      clinical factors in Han Chinese hospitalized patients with acutely exacerbated
      schizophrenia. MATERIALS AND METHODS: After hospitalization, the patients (n =
      128) were given a 4-week course of aripiprazole. Patients were genotyped for
      HTR2A A-1438G/T102C polymorphisms via the restriction fragment length
      polymorphism method. Clinical factors such as gender, age, duration of illness,
      education level, diagnostic subtype, and medication dosage were noted as well.
      The researchers measured psychopathology biweekly, using the Positive and
      Negative Syndrome Scale (PANSS). A mixed model regression approach (SAS Proc
      MIXED) was used to analyze the effects of genetic and clinical factors on PANSS
      performance after aripiprazole treatment. RESULTS: We found that the GG/CC
      genotype group of HTR2A A-1438G/T102C polymorphisms predicts poor aripiprazole
      response specifically for negative symptoms. In addition, the clinical factors,
      including dosage of aripiprazole, age, duration of illness, and diagnostic
      subtype, were found to influence PANSS performance after aripiprazole treatment.
      CONCLUSIONS: The data suggest HTR2A A-1438G/T102C polymorphisms may predict
      negative symptoms performance upon aripiprazole treatment in schizophrenic
      patients as modified by clinical factors.

PMID- 19387615
TI  - 5-HTT genotype effect on prefrontal-amygdala coupling differs between major
      depression and controls.
AB  - RATIONALE: In major depression, prefrontal regulation of limbic brain areas may
      be a key mechanism that is impaired during the processing of affective
      information. This prefrontal-limbic interaction has been shown to be modulated by
      serotonin (5-HTT) genotype, indicating a higher risk for major depressive
      disorder (MDD) with increasing number of 5-HTT low-expression alleles. OBJECTIVE:
      Functional magnetic resonance imaging was used to assess neural response to
      uncued unpleasant affective pictures in 21 unmedicated patients with MDD compared
      to 21 matched healthy controls, taking into account genetic influences of the 5
      HTT (SCL6A4) high- and low-expression genotype. RESULTS: Healthy controls
      displayed greater prefrontal activation (BA10) to uncued negative pictures
      compared to patients with MDD. While in healthy controls prefrontal (BA10)
      activation and BA10-amygdala coupling increased with the number of 5-HTT low
      expression risk alleles, this effect was abolished, and even reversed, in
      patients with MDD. In MDD, connectivity decreased with severity of depressive
      symptoms (HAMD total score). CONCLUSION: These findings suggest that increased
      medial prefrontal (BA10) activation and BA10-amygdala connectivity may counteract
      the risk for MDD in healthy carriers of 5-HTT low-expression alleles, while this
      protective factor might be lost in patients who actually suffer from MDD.
      Prefrontal-limbic regulation in risk populations could be a target of early
      interventions and should be the focus of further research.

PMID- 19387617
TI  - Anxiolytic-like effects induced by blockade of transient receptor potential
      vanilloid type 1 (TRPV1) channels in the medial prefrontal cortex of rats.
AB  - RATIONALE: The endocannabinoid anandamide, in addition to activating cannabinoid
      type 1 receptors (CB1), may act as an agonist at transient receptor potential
      vanilloid type 1 (TRPV1) channels. In the periaqueductal gray, CB1 activation
      inhibits, whereas TRPV1 increases, anxiety-like behavior. In the medial
      prefrontal cortex (mPFC), another brain region related to defensive responses,
      CB1 activation induces anxiolytic-like effects. However, a possible involvement
      of TRPV1 is still unclear. OBJECTIVES: In the present study, we tested the
      hypothesis that TRPV1 channel contributes to the modulation of anxiety-like
      behavior in the mPFC. MATERIALS AND METHODS: Male Wistar rats (n = 5-7 per group)
      received microinjections of the TRPV1 antagonist capsazepine (1-60 nmol) in the
      ventral portion of the mPFC and were exposed to the elevated plus maze (EPM) or
      to the Vogel conflict test. RESULTS: Capsazepine increased exploration of open
      arms in the EPM as well as the number of punished licks in the Vogel conflict
      test, suggesting anxiolytic-like effects. No changes in the number of entries
      into the enclosed arms were observed in the EPM, indicating that there were no
      changes in motor activity. Moreover, capsazepine did not interfere with water
      consumption or nociceptive threshold, discarding potential confounding factors
      for the Vogel conflict test. CONCLUSIONS: These data suggest that TRPV1 in the
      ventral mPFC tonically inhibits anxiety-like behavior. TRPV1 could facilitate
      defensive responses opposing, therefore, the anxiolytic-like effects reported
      after local activation of CB1 receptors.

PMID- 19387616
TI  - Treatment with escitalopram but not desipramine decreases escape latency times in
      a learned helplessness model using juvenile rats.
AB  - RATIONALE: The pharmacological treatment of depression in children and
      adolescents is different from that of adults due to the lack of efficacy of
      certain antidepressants in the pediatric age group. Our current understanding of
      why these differences occur is very limited. OBJECTIVES: To develop more
      effective treatments, a juvenile animal model of depression was tested to
      validate it as a possible model to specifically study pediatric depression.
      MATERIALS AND METHODS: Procedures for use with juvenile rats at postnatal day
      (PND) 21 and 28 were adapted from the adult learned helplessness model in which,
      24 h after exposure to inescapable stress, animals are unable to remove
      themselves from an easily escapable stressor. Rats were treated for 7 days with
      either the selective serotonin reuptake inhibitor escitalopram at 10 mg/kg or the
      tricyclic antidepressant desipramine at 3, 10, or 15 mg/kg to determine if
      treatment could decrease escape latency times. RESULTS: Escitalopram treatment
      was effective at decreasing escape latency times in all ages tested. Desipramine
      treatment did not decrease escape latency times for PND 21 rats, but did decrease
      times for PND 28 and adult animals. CONCLUSIONS: The learned helplessness model
      with PND 21 rats predicts the efficacy of escitalopram and the lack of efficacy
      of desipramine seen in the treatment of pediatric depression. These findings
      suggest that the use of PND 21 rats in a modified learned helplessness procedure
      may be a valuable model of human pediatric depression that can predict pediatric
      antidepressant efficacy and be used to study antidepressant mechanisms involved
      in pediatric depression.

PMID- 19387618
TI  - Competitive binding of cadmium by plant thiols: an electrochemical study assisted
      by multivariate curve resolution.
AB  - Multivariate curve resolution with alternating least squares (MCR-ALS) has been
      applied to voltammetric data obtained from analysis of the competitive binding of
      cysteine (Cys) and cysteine-glycine (Cys-Gly) by Cd(II) as a first approach
      towards mixtures of phytochelatins and related compounds in natural media. From
      different starting points, the possibilities of formation of mixed complexes
      and/or displacements between ligands are investigated. Analysis of the resulting
      unitary voltammograms and concentration profiles of the resolved components by
      MCR-ALS suggests that the strongest ligand (Cys-Gly) is able to displace the
      weakest (Cys) from its metal complexes, whereas this does not happen in the
      opposite direction. On the other hand, no evidence of Cd mixed-ligand complexes
      was found.

PMID- 19387619
TI  - Solid phase extraction for removal of matrix effects in lipophilic marine toxin
      analysis by liquid chromatography-tandem mass spectrometry.
AB  - The potential of solid phase extraction (SPE) clean-up has been assessed to
      reduce matrix effects (signal suppression or enhancement) in the liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis of lipophilic marine
      toxins. A large array of ion-exchange, silica-based, and mixed-function SPE
      sorbents was tested. Polymeric sorbents were found to retain most of the toxins.
      Optimization experiments were carried out to maximize recoveries and the
      effectiveness of the clean-up. In LC-MS/MS analysis, the observed matrix effects
      can depend on the chromatographic conditions used, therefore, two different HPLC
      methods were tested, using either an acidic or an alkaline mobile phase. The
      recovery of the optimized SPE protocol was around 90% for all toxins studied and
      no break-through was observed. The matrix effects were determined by comparing
      signal response from toxins spiked in crude and SPE-cleaned extracts with those
      derived from toxins prepared in methanol. In crude extracts, all toxins suffered
      from matrix effects, although in varying amounts. The most serious effects were
      observed for okadaic acid (OA) and pectenotoxin-2 (PTX2) in the positive
      electrospray ionization mode (ESI(+)). SPE clean-up on polymeric sorbents in
      combination with the alkaline LC method resulted in a substantial reduction of
      matrix effects to less than 15% (apparent recovery between 85 and 115%) for OA,
      yessotoxin (YTX) in ESI(-) and azaspiracid-1 (AZA1), PTX2, 13-desmethyl
      spirolides C (SPX1), and gymnodimine (GYM) in ESI(+). In combination with the
      acidic LC method, the matrix effects after SPE were also reduced but nevertheless
      approximately 30% of the matrix effects remained for PTX2, SPX1, and GYM in
      ESI(+). It was concluded that SPE of methanolic shellfish extracts can be very
      useful for reduction of matrix effects. However, the type of LC and MS methods
      used is also of great importance. SPE on polymeric sorbents in combination with
      LC under alkaline conditions was found the most effective method.

PMID- 19387620
TI  - Toxicological study of pesticides in air and precipitations of Paris by means of
      a bioluminescence method.
AB  - A detailed toxicological study on several pesticides, including chlorothalonil,
      cyprodynil, dichlobenil, pendimethaline, trifluraline, and alpha-endosulfan,
      present at trace levels in air and total atmospheric precipitations of Paris is
      presented. The pesticides contained in the atmospheric samples, collected during
      sampling campaigns in February-March 2007, are identified and quantified by a
      high-performance liquid chromatographic (HPLC)-UV detection method. The toxicity
      measurements are performed by means of the Microtox bioluminescence method, based
      on the evaluation of the bioluminescence inhibition of the Vibrio fischeri marine
      bacteria at two exposure times to the pesticide solutions. The specific toxicity,
      corresponding to the particular toxicity of the compound under study and
      represented by the EC(50) parameter, is determined for these pesticides. Also,
      the global toxicity, which is the toxicity of all micro-pollutants present in the
      sample under study, is estimated for the extracts of air and atmospheric
      precipitation (rainwater) samples. The specific toxicities strongly vary with the
      nature of the pesticide, the EC(50) parameter values being comprised between 0.17
      and 0.83 mg/mL and 0.15 and 0.66 mg/mL, respectively, for exposure times of 5 and
      15 min. The importance of the atmospheric samples' global toxicity and the
      respective contribution of the toxic potency of the various pesticides contained
      in these samples are discussed.

PMID- 19387621
TI  - Application of dried blood spots combined with high-performance liquid
      chromatography coupled with electrospray ionisation tandem mass spectrometry for
      simultaneous quantification of vincristine and actinomycin-D.
AB  - A sensitive, specific and efficient high-performance liquid chromatography-tandem
      mass spectrometry assay for the simultaneous determination of vincristine and
      actinomycin-D in human dried blood spots is presented. Dried blood spots were
      punched out of a collection paper with a 0.25-in.-diameter punch. The analytes
      were extracted from the punched-out disc using sonication during 15 min in a
      mixture of acetonitrile-methanol-water (1:1:1, v/v/v) containing the internal
      standard vinorelbine. Twenty-microlitre volumes were injected onto the HPLC
      system. Separation was achieved on a 50 x 2.1 mm ID Xbridge C(18) column using
      elution with 1 mM ammonium acetate-acetonitrile (70:30, v/v) adjusted to pH 10.5
      with ammonia and run in a gradient with methanol at a flow rate of 0.4 mL/min.
      HPLC run time was 6 min. The assay quantifies vincristine from 1 to 100 ng/mL and
      actinomycin-D from 2 to 250 ng/mL using a blood sample obtained by a simple
      finger prick. Validation results demonstrate that vincristine and actinomycin-D
      can be accurately and precisely quantified in human dried blood spots with the
      presented method. The assay can now be used to support clinical pharmacologic
      studies with vincristine and actinomycin-D.

PMID- 19387622
TI  - Automated on-line in-tube solid-phase microextraction coupled with HPLC/MS/MS for
      the determination of butyrophenone derivatives in human plasma.
AB  - This paper describes a fully automated on-line method combining in-tube solid
      phase microextraction (SPME) in which sample clean-up and enrichment are
      conducted through an open tubular fused-silica capillary column and high
      performance liquid chromatography (HPLC)/tandem mass spectrometry (MS/MS)
      detection for the determination of six butyrophenone derivatives (moperone,
      floropipamide, haloperidol, spiroperidol, bromperidol, and pimozide) in human
      plasma samples. The six butyrophenones were extracted by repeatedly aspirating
      and dispensing plasma sample solutions on a DB-17 capillary column (60 cm x 0.32
      mm i.d., film thickness 0.25 microm). The analytes retained on the inner surface
      of the capillary column were then eluted into an acetonitrile-rich mobile phase
      using a gradient separation technique. Extraction efficiencies ranged from 12.7%
      to 31.8% for moperone, spiroperidol, and pimozide, and from 1.08% to 4.86% for
      floropipamide, haloperidol, and bromperidol. The regression equations for all
      compounds showed excellent linearity, ranging from 0.05 to 50 ng/0.1 mL of
      plasma, except for moperone and spiroperidol (0.01 to 50 ng/0.1 mL). The limits
      of detection and quantification in plasma for each drug were 0.03-0.2 and 0.1-0.5
      ng/mL, respectively. The intra- and inter-day coefficients of variation for all
      compounds in plasma were not greater than 13.7%.

PMID- 19387623
TI  - European analytical column no. 37 (January 2009).

PMID- 19387624
TI  - Response preparation changes during practice of an asynchronous bimanual
      movement.
AB  - For synchronous bimanual movements, we have shown that a different amplitude can
      be prepared for each limb in advance and this preparation improves with practice
      (Maslovat et al. 2008). In the present study, we tested whether an asynchronous
      bimanual movement can also be prepared in advance and be improved with practice.
      Participants practiced (160 trials) a discrete bimanual movement in which the
      right arm led the left by 100 ms in response to an auditory "go" signal (either
      80 dB control stimulus or 124 dB startle stimulus). The startle stimulus was used
      to gauge whether inter-limb timing could be pre-programed. During startle trials,
      the asynchronous bimanual movement was triggered at early latency suggesting the
      entire movement could be prepared in advance. However, the triggered movement had
      a shorter between-arm delay and a temporally compressed within-arm EMG pattern,
      results that we attribute to increased neural activation caused by the startling
      stimulus. However, as both startle and control trials improved over time, it does
      appear response preparation of interval timing can improve with practice.

PMID- 19387625
TI  - Attentional modulation of perceived pain intensity in capsaicin-induced secondary
      hyperalgesia.
AB  - Perceived pain intensity is modulated by attention. However, it is not known that
      how pain intensity ratings are affected by attention in capsaicin-induced
      secondary hyperalgesia. Here we show that perceived pain intensity in secondary
      hyperalgesia is decreased when attention is distracted away from the painful
      pinprick stimulus with a visual task. Furthermore, it was found that the
      magnitude of attentional modulation in secondary hyperalgesia is very similar to
      that of capsaicin-untreated, control condition. Our findings, showing no
      interaction between capsaicin treatment and attentional modulation suggest that
      capsaicin-induced secondary hyperalgesia and attention might affect mechanical
      pain through independent mechanisms.

PMID- 19387626
TI  - Exploring warfarin pharmacogenomics with the extreme-discordant-phenotype
      methodology: impact of FVII polymorphisms on stable anticoagulation with
      warfarin.
AB  - PURPOSE: To explore the pharmacogenomics of warfarin using the extreme-discordant
      phenotype (EDP) methodology. METHODS: The target phenotype was the stable
      warfarin dose prescribed to 353 patients. Pharmacogenetic polymorphisms assessed
      were coagulation factor VII (FVII) -401G>T and FVII -402G>A, VKORC1 3673G>A, and
      CYP2C9*2, *3, *5, and *11 alleles. The EDP analyses contrasted the frequencies of
      these polymorphisms at different cutoff points (5th through 30th percentiles of
      the warfarin dose distribution) at opposite ends of the warfarin dose
      distribution. RESULTS: Significant differences existed in FVII -402G>A genotype
      frequency at the 5th percentile with an over-representation of the wildtype GG
      genotype at low warfarin doses and in VKORC1 3673G>A and CYP2C9 polymorphisms at
      all cutoff points where the variant alleles were overrepresented at low warfarin
      doses. CONCLUSION: The EDP methodology provides increased statistical power for
      detection of small contributions of genetic polymorphisms to multiple drug
      response phenotypes, such as warfarin dose requirement for adequate
      anticoagulation.

PMID- 19387627
TI  - Evidence suggesting a genetic contribution to kidney stone in northeastern Thai
      population.
AB  - Genetic factor may play a role in the pathogenesis of kidney stone that is found
      in the northeastern (NE) Thai population. Herein, we report initial evidence
      suggesting genetic contribution to the disease in this population. We examined
      1,034 subjects including 135 patients with kidney stone, 551 family members, and
      348 villagers by radiography of kidney-ureter-bladder (KUB) and other methods,
      and also analyzed stones removed by surgical operations. One hundred and sixteen
      of 551 family members (21.05%) and 23 of the 348 villagers (6.61%) were affected
      with kidney stone. The relative risk (lambda(R)) of the disease among family
      members was 3.18. Calcium stones (whewellite, dahllite, and weddellite) were
      observed in about 88% of stones analyzed. Our data indicate familial aggregation
      of kidney stone in this population supporting that genetic factor should play
      some role in its pathogenesis. Genetic and genomic studies will be conducted to
      identify the genes associated with the disease.

PMID- 19387628
TI  - Embryonal rhabdomyosarcoma of the omentum: two cases occurring in children.
AB  - Rhabdomyosarcoma is a soft-tissue malignancy that represents approximately 4-8%
      of all solid tumours in children and commonly arises from the head and neck and
      genitourinary system. Intraperitoneal rhabdomyosarcoma, in particular with
      omental involvement, has been rarely reported in the literature. Furthermore,
      reports of omental rhabdomyosarcoma of embryonal origin do not exist, to our
      knowledge. We report two cases of omental embryonal rhabdomyosarcoma affecting
      children and illustrate the imaging characteristics of this rare tumour.

PMID- 19387629
TI  - A different image of avoiding sedation in pediatric radiology.

PMID- 19387630
TI  - Head and neck lymph nodes in children: the spectrum from normal to abnormal.
AB  - Lymphadenopathy of the head and neck region is a common finding in children and a
      very common reason to image the craniocervical region. Enlarged lymph nodes are
      commonly palpated by the pediatrician in the office and commonly imaged by the
      pediatric radiologist. The difficult task of the clinician is to determine
      whether the adenopathy is acute (<3 weeks) or chronic (>6 weeks) and when imaging
      is indicated. In children, radiation is always a consideration when choosing an
      imaging modality; thus, US is usually the first imaging study at our institution,
      and CT the second option, usually reserved for the very ill child or for when
      there is a high index of suspicion for malignancy. We present the normal anatomy
      of head and neck lymph nodes and the US, CT, and MRI appearances in normal and
      pathologic states to help clinicians generate a reasonable differential diagnosis
      and prevent unnecessary procedures.

PMID- 19387631
TI  - Neuroimaging findings in a child with dumbbell-shaped frontosphenoidal dermoid
      cyst presenting as preseptal cellulitis.
AB  - We report the CT and MRI findings in a 5-year-old girl with histologically proven
      frontosphenoidal dumbbell-shaped dermoid cyst with sinus tracts in the frontal
      bone extending to the dura. Although the most common location for dermoid cyst in
      the head and neck is at the frontosphenoidal region, presentation with a tract
      extending deep to underlying bone or the intracranium is rare for this location.
      Complete surgical excision has been widely accepted as the basic treatment for
      dermoid cyst. However, the relatively extensive nature of such surgical
      interventions may be associated with serious risks to both visual acuity and
      cosmesis. From a clinical viewpoint, even if these are rare cases, radiological
      imaging is crucial for orienting the deeper extension of the lesion for
      presurgical planning.

PMID- 19387632
TI  - Comments on imaging and management of hepatic hemangiomas.

PMID- 19387634
TI  - Overproduction of poly-beta-hydroxybutyrate in the Azotobacter vinelandii mutant
      that does not express small RNA ArrF.
AB  - Azotobacter vinelandii contains an iron-regulatory small RNA ArrF whose
      expression is dependent upon the levels of iron and ferric uptake regulator. The
      deletion of this ArrF-encoding gene resulted in a 300-fold increase in the
      production of poly-beta-hydroxybutyrate (PHB), a polymer of industrial
      importance. This arrF mutant exhibited wild-type growth and growth-associated PHB
      production. Limited iron and aeration elevated the PHB production in the mutant
      as well as wild type. Real-time RT-PCR revealed that phbB, phbA, and phbC were
      upregulated approximately 61-, 18-, and eightfold, respectively, in the mutant.
      The phbR transcript of the activator PhbR for this operon was also approximately
      11 times more abundant. The analysis of phbR transcript predicted a region of
      complementarity near its Shine-Dalgarno sequence that could potentially basepair
      with the conserved region of ArrF. These results suggest that ArrF represses the
      expression of PhbR in an antisense manner and derepression of this activator in
      the mutant elevates the expression of phbB, phbA, and phbC, resulting in the PHB
      overproduction.

PMID- 19387633
TI  - Oxidation promotes insertion of the CLIC1 chloride intracellular channel into the
      membrane.
AB  - Members of the chloride intracellular channel (CLIC) family exist primarily as
      soluble proteins but can also auto-insert into cellular membranes to form ion
      channels. While little is known about the process of CLIC membrane insertion, a
      unique feature of mammalian CLIC1 is its ability to undergo a dramatic structural
      metamorphosis between a monomeric glutathione-S-transferase homolog and an all
      helical dimer upon oxidation in solution. Whether this oxidation-induced
      metamorphosis facilitates CLIC1 membrane insertion is unclear. In this work, we
      have sought to characterise the role of oxidation in the process of CLIC1
      membrane insertion. We examined how redox conditions modify the ability of CLIC1
      to associate with and insert into the membrane using fluorescence quenching
      studies and a sucrose-loaded vesicle sedimentation assay to measure membrane
      binding. Our results suggest that oxidation of monomeric CLIC1, in the presence
      of membranes, promotes insertion into the bilayer more effectively than the
      oxidised CLIC1 dimer.

PMID- 19387635
TI  - New proteins orthologous to cerato-platanin in various Ceratocystis species and
      the purification and characterization of cerato-populin from Ceratocystis
      populicola.
AB  - Natural variants of cerato-platanin (CP), a pathogen associated molecular pattern
      (PAMP) protein produced by Ceratocystis platani (the causal agent of the plane
      canker stain), have been found to be produced by other four species of the genus
      Ceratocystis, including five clones of Ceratocystis fimbriata isolated from
      different hosts. All these fungal strains were known to be pathogenic to plants
      with considerable importance in agriculture, forestry, and as ornamental plants.
      The putative premature proteins were deduced on the basis of the nucleotide
      sequence of genes orthologous to the cp gene of C. platani; the deduced premature
      proteins of Ceratocystis populicola and Ceratocystis variospora reduced the total
      identity of all the others from 87.3% to 60.3%. Cerato-populin (Pop1), the CP
      orthologous protein produced by C. populicola, was purified and characterized.
      Pop1 was a well-structured alpha/beta protein with a different percentage of the
      alpha-helix than CP, and it self-assembled in vitro in ordered aggregates.
      Moreover, Pop1 behaved as PAMP, since it stimulated poplar leaf tissues to
      activate defence responses able to reduce consistently the C. populicola growth.

PMID- 19387636
TI  - Bilateral tight swollen legs: diagnosis and discussion.

PMID- 19387638
TI  - Multifaceted role of lymphatic mapping by SPECT/CT hybrid imaging in the
      multimodality management of patients with cancer.

PMID- 19387639
TI  - [(18)F]Fluoroacetate is not a functional analogue of [(11)C]acetate in normal
      physiology.
AB  - PURPOSE: [(11)C]Acetate (C-AC) is a general PET tracer of cellular carbon flux
      and useful for clinical imaging in heart disease as well as prostate cancer and
      other tumours. C-AC has a high (70%) whole-body extraction fraction, proportional
      to blood flow in many organs. Trapping is related to organ-specific enzymatic
      activation and formation of [(11)C]-acetyl-CoA, the fate of which has been well
      characterized. Due to the logistic challenges with C-AC, 2-[(18)F]fluoroacetate
      (F-AC) has been proposed as a marker for prostate cancer imaging. METHOD: We
      evaluated the potential of F-AC as a tracer for imaging blood flow and early
      enzymatic steps in the intermediary metabolism. C-AC and F-AC were injected
      serially in three cynomolgus monkeys and one domestic pig and scanned using
      PET/CT. A dynamic scan covering heart and liver was followed by repeated whole
      body imaging. Kinetic patterns were compared for the myocardium, liver, blood and
      other organs. RESULTS: C-AC kinetics and organ distribution in both species were
      similar to those previously established in man. In contrast, F-AC showed
      prolonged blood retention, no detectable trapping in myocardium or salivary
      glands, rapid clearance from liver and extensive excretion to bile and urine.
      Massive defluorination was seen in the pig, resulting in intense skeletal
      activity. CONCLUSION: 2-[(18)F]Fluoroacetate cannot be regarded as a functional
      analogue of 1-[(11)C]acetate in normal physiology and appears to be of little use
      for studies of organ blood flow, intermediary metabolism or lipid synthesis.

PMID- 19387640
TI  - Quantitative relationship between coronary calcium content and coronary flow
      reserve as assessed by integrated PET/CT imaging.
AB  - PURPOSE: To evaluate the relationship between coronary artery calcium (CAC) and
      coronary vasodilator function. METHODS: We evaluated 136 patients without known
      coronary artery disease (CAD) undergoing vasodilator stress (82)Rb PET/CT and CAC
      scoring who showed normal myocardial perfusion. The CAC score, resting and
      hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR) and coronary
      vascular resistance were analyzed. RESULTS: Global and regional CAC scores showed
      significant but weak inverse correlations with hyperemic MBF (r=-0.31 and r=
      0.26, p< or =0.0002 respectively) and CFR (r=-0.28 and r=-0.2, p< or =0.001
      respectively). With increasing CAC score, there was a modest stepwise decline in
      CFR on a per-patient basis (1.8+/-0.5 vs 1.7+/-0.5 vs 1.5+/-0.4, p=0.048, with
      total CAC=0, 1-400 and >400, respectively) and on a per-vessel basis. In
      multivariable modeling only body mass index and CAC score were predictive of CFR.
      CONCLUSION: In patients with an intermediate likelihood of, but without overt,
      CAD, there is a statistically significant but weak inverse correlation between
      CAC content and coronary vasodilator function. The strength of this association
      weakens after adjusting CAC scores for age, gender and coronary risk factors.
      This suggests that CAC and coronary vasodilator function provide biologically
      different information regarding atherosclerosis.

PMID- 19387641
TI  - Chondroblastoma of the femoral head: management and outcome.
AB  - Chondroblastoma of the femoral head presents particular problems in treatment
      because the tumour is surrounded by articular cartilage on one side and
      epiphyseal plate on the other. Ten patients underwent treatment for a
      chondroblastoma involving the proximal femoral capital epiphysis. The patients
      were aged between eight and 19 years and in four the epiphysis was not yet fused.
      Five had curettage via a drill hole created up the femoral neck, of whom two
      developed local recurrence. Five had a direct approach to the chondroblastoma
      through the femoral neck, and there were no local recurrences in this group. Both
      patients with local recurrence were under 14 years of age-one was cured by a
      direct approach through the neck of the femur and the other by lifting a trap
      door of articular cartilage. Apart from one patient with a temporary leg length
      discrepancy, there were no other complications. We conclude that a direct
      approach is likely to lead to the best outcome for this rare condition.

PMID- 19387642
TI  - Biomechanical and histological comparison of the influence of oestrogen deficient
      state on tendon healing potential in rats.
AB  - Thirty-six female Sprague-Dawley rats were divided into two groups:
      oophrectomised (oestrogen deficient) rats and sham operated (oestrogen
      maintained) rats. Rats were sacrificed at six, ten, and 14 weeks. The rats were
      randomly chosen to have biomechanical evaluation on one side and histological
      evaluation on the other. Biomechanical testing was performed on an Instron
      machine to measure peak load. Histological sections were evaluated for cell
      proliferation, collagen-fibre organisation, fibroblast density, angiogenesis,
      inflammatory cells, chondroid and osseous metaplasia. Compared with the sham
      operated group, the oophrectomised group showed a lesser average maximum stress
      (42.9 N/m(2) versus 33.7 N/m(2)) at six weeks, which was significant (p < .05).
      Succeeding weeks showed no significant biomechanical differences between the two
      groups. The sham operated group showed greater inflammatory response, which was
      statistically significant (p < 0.05), and also revealed greater cell
      proliferation and density. The results of this study revealed that endogenous
      oestrogen may improve healing of the Achilles tendon in rats.

PMID- 19387643
TI  - In vivo knee kinematics during high flexion after a posterior-substituting total
      knee arthroplasty.
AB  - The objective of this study was to investigate biomechanics of TKA patients
      during high flexion. Six patients (seven knees) with a posterior-substituting TKA
      and weight-bearing flexion >130 degrees were included in the study. The six
      degree-of-freedom kinematics, tibiofemoral contact, and cam-post contact were
      measured during a deep knee bend using dual-plane fluoroscopy. The patients
      achieved average weight-bearing flexion of 139.5 +/- 4.5 degrees. Posterior
      femoral translation and internal tibial rotation increased steadily beyond 90
      degrees flexion, and a sharp increase in varus rotation was noted at maximum
      flexion. Initial cam-post engagement was observed at 100.3 +/- 6.7 degrees
      flexion. Five knees had cam-post disengagement before maximum flexion. Lateral
      femoral condylar lift-off was found in five out of seven knees at maximum
      flexion, and medial condylar lift-off was found in one knee. Future studies
      should investigate if the kinematic characteristics of posterior-substituting TKA
      knees noted in this study are causative factors of high knee flexion.

PMID- 19387644
TI  - Long-term results of hip arthroplasty in ambulatory patients with cerebral palsy.
AB  - Osteoarthritis (OA) secondary to dislocation and dysplasia is a common problem in
      patients with cerebral palsy. The purpose of this study was to evaluate the
      results of total hip replacement (THR) in ambulatory patients with cerebral
      palsy. Eighteen total hip arthroplasties were performed in 16 ambulatory patients
      with cerebral palsy. The patient's mean age at surgery was 42 +/- 8 years (range
      32-58 years), and the mean follow-up was 10 +/- 6 years (range 2-18 years). Data
      were obtained by a standardised telephone interview. There was a significant
      postoperative reduction in pain on the NAS (narrative analogue scale) from 8.4
      preoperatively to 1.1 postoperatively (p = 0.002). At follow-up no stem had been
      revised. Three cups were revised for aseptic loosening at two and six years, and
      one cup was revised for recurrent dislocation of the hip. One hip was revised for
      infection 12 years after the index surgery. One hip dislocated (three months
      postoperatively) and was treated by closed reduction. In ambulatory patients with
      cerebral palsy and secondary osteoarthritis of the hip THR can provide long-term
      pain relief and improved function. The rate of long term complications was
      moderate in this series; however, the dislocation rate was higher than in
      standard OA cases.

PMID- 19387645
TI  - PNAS-4, a novel pro-apoptotic gene, can potentiate antineoplastic effects of
      cisplatin.
AB  - PURPOSE: PNAS-4, a novel pro-apoptotic gene activated during the early response
      to DNA damage, can inhibit proliferation via apoptosis when overexpressed in some
      tumor cells. The objectives of this study were to determine whether PNAS-4 could
      enhance apoptosis induced by cisplatin besides its induction of apoptosis, and to
      evaluate the usefulness of combined treatment with mouse PNAS-4 (mPNAS-4) gene
      therapy and low-dose cisplatin chemotherapy in the inhibition of tumor growth in
      colon carcinoma (CT26) and Lewis lung carcinoma (LL/2) murine models. METHODS: In
      this study, the in vitro growth-inhibitory and pro-apoptotic effects of PNAS-4
      and/or cisplatin on CT26, LL/2, and SKOV3 cancer cells were assessed by MTT
      assay, flow cytometric analysis, DNA fragmentation, and morphological analysis,
      respectively. The in vivo antitumor activity of combined treatment with mPNAS-4
      gene therapy and low-dose cisplatin were evaluated in the inhibition of tumor
      growth in colon carcinoma (CT26) and Lewis lung carcinoma (LL/2) murine models.
      Tumor volume and survival time were observed. Induction of apoptosis was also
      assessed in tumor tissues. RESULTS: In vitro, PNAS-4 inhibited proliferation of
      colon carcinoma (CT26), Lewis lung carcinoma (LL/2) and human ovarian cancer
      (SKOV3) cell lines via apoptosis, and significantly enhanced the apoptosis of
      CT26, LL/2, and SKOV3 cells induced by cisplatin. In vivo systemic administration
      of expression plasmid encoding mPNAS-4 (pcDNA3.1-mPS) and cisplatin,
      significantly decreased tumor growth through increased tumor cell apoptosis
      compared to treatment with mPNAS-4 or cisplatin alone. CONCLUSIONS: Our data
      suggests that the combined treatment with mPNAS-4 plus cisplatin may augment the
      induction of apoptosis in tumor cells in vitro and in vivo, and that the
      augmented antitumor activity in vivo may result from the increased induction of
      apoptosis. The present study may provide a novel way to augment the antitumor
      efficacy of cytotoxic chemotherapy.

PMID- 19387646
TI  - Long-term anti-tumour necrosis factor therapy reverses the progression of carotid
      intima-media thickness in female patients with active rheumatoid arthritis.
AB  - The objective of the study is to evaluate the effect of TNF inhibition on carotid
      thickness over a 2-year period. 144 women with RA diagnosed according to ACR
      criteria, without clinical evidence of cardiac and/or vascular disease were
      enrolled and compared with 78 matched controls. All patients received
      methotrexate (15-20 mg weekly) for 3 months. Responders (n = 79) continued to be
      treated with methotrexate, non-responders (n = 40) moved to methotrexate plus a
      TNF alpha antagonist. Echosonographic studies of carotids were obtained before
      and after 2-year follow-up. A significant decrease of ca-IMT was observed in anti
      TNF-treated patients (P < 0.001); on the other hand, no significant variation of
      ca-IMT was observed after 2 years in MTX-treated patients. Our study indicates
      that anti-TNF blocking agents, but not methotrexate, are capable of reducing IMT
      of carotid arteries in female RA patients in a 2-year follow-up.

PMID- 19387647
TI  - IL-18 105 A>C polymorphism contributes to renal manifestations in patients with
      SLE.
AB  - Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue
      disorder characterized by various aberrations including increased production of
      IL-18. As IL-18 105 A>C polymorphic variants have been linked to increased
      production of this cytokine, we investigated the prevalence of IL-18 105 A>C
      (rs549908) polymorphic variants in SLE patients (n = 111) and controls (n = 152).
      There were no significant differences in the distribution of IL-18 105 A>C
      polymorphic variants in SLE patients and controls. However, there was a
      significant association between the IL-18 105 AA genotype (recessive model) and
      renal manifestations OR = 3.360 (1.523-7.415, P = 0.0039) and the P value
      remained statistically significant after Bonferroni correction (P corr =
      0.0351).Our findings indicate that the IL-18 105 AA genotype variant can
      contribute to renal manifestations in patients with SLE.

PMID- 19387648
TI  - In-office magnetic resonance imaging to monitor responses to therapy in
      rheumatoid arthritis.
AB  - Low-field extremity magnetic resonance imaging (MRI) has been developed as an
      alternative method for detecting inflammatory changes and structural damage
      associated with rheumatoid arthritis (RA). Studies have shown that extremity MRI
      is able to predict future joint damage in patients with early RA and is more
      sensitive than conventional radiography at detecting joint erosions. This report
      uses four different cases to illustrate how extremity MRI can be used to monitor
      disease activity and inform treatment decisions during the management of RA in
      the routine clinical practice setting.

PMID- 19387649
TI  - Clinical features and renal outcome in lupus patients with diffuse crescentic
      glomerulonephritis.
AB  - The objectives of the study are to investigate the clinical features and renal
      outcomes in lupus patients with diffuse crescentic glomerulonephritis (DCGN).
      Ninety-four DCGN lupus patients were enrolled. Their clinical features and renal
      outcomes were investigated. There were 84 females and 10 males, with a mean age
      of 27.9 +/- 10.7 years old. They represented: hypertension in 73 cases (77.7%),
      rapidly progressive glomerulonephritis in 62 cases (66.0%), 46 cases (48.9%) with
      nephritic syndrome, 35 (37.2%) gross hematuria, and 14 cases (14.9%) with uremic
      syndrome needed dialysis therapy. There were 25 cases received repeated renal
      biopsy. Their histological examination showed the decreasing of active lesions
      and the increasing chronic lesions. All patients were more than 6 months follow
      up, and 79 patients (84.0%) were more than 12 months follow-up. At the first time
      of follow-up (3 months), the renal function, proteinuria, and anemia were
      improved significantly in all of cases received intensive immunosuppressive
      therapy. At the last time of follow-up (56.1 +/- 18.8 months), only four patients
      eventually developed to the end-stage renal failure and five died with normal
      renal function. The lupus patients with DCGN presented more severe clinical
      syndromes, which were similar to those patients of type II of DCGN. The relative
      good renal outcomes were observed in those lupus patients, to which may be
      contribute to the effective induction therapy.

PMID- 19387650
TI  - CT-guided radiofrequency ablation of spinal osteoid osteomas with concomitant
      perineural and epidural irrigation for neuroprotection.
AB  - Here we report our experience of a neuroprotective adaptation of the technique of
      CT-guided radiofrequency (RF) ablation of spinal osteoid osteomas. Over 9 years
      seven patients underwent eight CT-guided RF treatments for osteoid osteoma. CT
      guided RF ablation was performed with general anaesthesia. The lesion was heated
      to 90 degrees C for 2 min for two cycles by using a Cosman SMK TC-10 RF
      electrode. This was preceded by a bolus of room temperature sterile water (10 ml)
      injected through a 26G curved spinal needle into the exit foramen and adjacent
      epidural space for neuroprotection. The age of the patient, sex, lesion location,
      biopsy results and complications were recorded. All the biopsies (n = 7)
      demonstrated histological features of osteoid osteoma. All the procedures were
      technically successful. Clinical success was assessed up to 3 years post
      procedure. There was an 85% clinical success rate (6 of the 7 patients), with
      recurrence of a lesion at 6 months, necessitating a repeat procedure
      (successful). CT-guided percutaneous RF ablation of spinal osteoid osteoma
      preceded by bolus of sterile water, injected through a spinal needle into the
      exit foramen and adjacent epidural space for neuroprotection, is a safe and
      effective procedure.

PMID- 19387651
TI  - Coronary calcium score as gatekeeper for 64-slice computed tomography coronary
      angiography in patients with chest pain: per-segment and per-patient analysis.
AB  - We sought to investigate the performance of 64-slice CT in symptomatic patients
      with different coronary calcium scores. Two hundred patients undergoing 64-slice
      CT coronary angiography for suspected coronary artery disease were enrolled into
      five groups based on Agatston calcium score using the Mayo Clinic risk
      stratification: group 1: score 0, group 2: score 1-10, group 3: score 11-100,
      group 4: score 101-400, and group 5: score > 401. Diagnostic accuracy for the
      detection of significant (>/=50% lumen reduction) coronary artery stenosis was
      assessed on a per-segment and per-patient base using quantitative coronary
      angiography as the gold standard. For groups 1 through 5, sensitivity was 97, 96,
      91, 90, 92%, and specificity was 99, 98, 96, 88, 90%, respectively, on a per
      segment basis. On a per-patient basis, the best diagnostic performance was
      obtained in group 1 (sensitivity 100% and specificity 100%) and group 5
      (sensitivity 95% and specificity 100%). Progressively higher coronary calcium
      levels affect diagnostic accuracy of CT coronary angiography, decreasing
      sensitivity and specificity on a per-segment base. On a per-patient base, the
      best results in terms of diagnostic accuracy were obtained in the populations
      with very low and very high cardiovascular risk.

PMID- 19387652
TI  - Evidence for a perception of prosodic cues in bat communication: contact call
      classification by Megaderma lyra.
AB  - The perception of prosodic cues in human speech may be rooted in mechanisms
      common to mammals. The present study explores to what extent bats use rhythm and
      frequency, typically carrying prosodic information in human speech, for the
      classification of communication call series. Using a two-alternative, forced
      choice procedure, we trained Megaderma lyra to discriminate between synthetic
      contact call series differing in frequency, rhythm on level of calls and rhythm
      on level of call series, and measured the classification performance for stimuli
      differing in only one, or two, of the above parameters. A comparison with
      predictions from models based on one, combinations of two, or all, parameters
      revealed that the bats based their decision predominantly on frequency and in
      addition on rhythm on the level of call series, whereas rhythm on level of calls
      was not taken into account in this paradigm. Moreover, frequency and rhythm on
      the level of call series were evaluated independently. Our results show that
      parameters corresponding to prosodic cues in human languages are perceived and
      evaluated by bats. Thus, these necessary prerequisites for a communication via
      prosodic structures in mammals have evolved far before human speech.

PMID- 19387653
TI  - Activity affects intraspecific body-size scaling of metabolic rate in ectothermic
      animals.
AB  - Metabolic rate is commonly thought to scale with body mass (M) to the 3/4 power.
      However, the metabolic scaling exponent (b) may vary with activity state, as has
      been shown chiefly for interspecific relationships. Here I use a meta-analysis of
      literature data to test whether b changes with activity level within species of
      ectothermic animals. Data for 19 species show that b is usually higher during
      active exercise (mean +/- 95% confidence limits = 0.918 +/- 0.038) than during
      rest (0.768 +/- 0.069). This significant upward shift in b to near 1 is
      consistent with the metabolic level boundaries hypothesis, which predicts that
      maximal metabolic rate during exercise should be chiefly influenced by volume
      related muscular power production (scaling as M (1)). This dependence of b on
      activity level does not appear to be a simple temperature effect because body
      temperature in ectotherms changes very little during exercise.

PMID- 19387654
TI  - Cytogenetic findings in a rare pediatric mixed glioneuronal tumor and review of
      the literature.
AB  - OBJECTIVE: The aim of the present study was to report the chromosomal
      abnormalities findings in rare pediatric mixed glioneuronal tumor (GNT), which
      could not be classified according to the WHO classification. METHODS: Cytogenetic
      studies were performed using G-banding and fluorescence in situ hybridization
      (FISH) techniques. RESULTS: Cytogenetic analyses showed a deletion of 1p as
      primary genetic event and gain of chromosome 7 as secondary change. Furthermore,
      we present a review of available cytogenetic data of 72 pediatric patients with
      GNT. Taken into account these data and the present case, we found that the most
      frequent chromosomal anomalies involved gains of chromosomes 7 (15.1%), 5 (8.2%),
      1q32-qter (6.8%), 8p21-qter (6.8%), 12 (5.5%), 18 (5.5%), 20q11-qter (5.5%), and
      X (5.5%). Frequent losses were detected on chromosome regions 1p (8.2%) and 22q
      (5.5%). CONCLUSION: The findings of our case combined with those of previous
      reports suggest that chromosomes 1 and 7 may contain candidate genes involved in
      the tumorigenesis of GNT.

PMID- 19387656
TI  - Focus Session "Changing epidemiology in pediatric neurosurgery".

PMID- 19387655
TI  - Survival following treatment for intracranial ependymoma: a review.
AB  - The actual definition of survival rates following treatment for intracranial
      ependymomas is substantially influenced by the strict interaction among different
      factors. Age, location, and grading, for example, act together, negatively
      influencing the prognosis of younger children also invariably influenced by the
      more demanding role of surgery and the still limited use, up to recently, of
      radiotherapy under 3 years of age. In the same direction, the worse prognosis in
      most series of infratentorial ependymomas if compared with their supratentorial
      counterpart should be cautiously considered, midline posterior fossa tumors
      having completely different implications from those originating or predominantly
      extending to the cerebellopontine angle, where the extent of surgery has more
      invariably to compare with patients' quality of life. New radiotherapic regimens
      and their applications in infancy are promisingly demonstrating an improvement of
      present prognostic criteria, with the limit of still insufficient information on
      their long-term secondary effects. Similarly, molecular biology research studies,
      though still in their preclinical stage, are prompting to change the concept of a
      substantially chemoresistant tumor helping to stratify these lesions with the
      final aim of targeted pharmacological therapies. In the present review paper, we
      investigated singularly the role that the more commonly considered prognostic
      factors have had in the literature on survival of children affected by
      intracranial ependymomas, trying to elucidate their cumulative effect on the
      actual knowledge of this issue.

PMID- 19387657
TI  - Cover picture. The precious qualities of a "fossil" tree.

PMID- 19387658
TI  - A rare case of intra-cardiac metastasis from an appendiceal carcinoid tumour
      without liver metastases.

PMID- 19387659
TI  - Spatiotemporal pattern analysis of transcription factor 4 in the developing
      anorectum of the rat embryo with anorectal malformations.
AB  - PURPOSE: As a member of the transcription factors family, transcription factor
      4(Tcf4) is known to influence gene expression in endodermally derived tissues
      including lung, liver, pancreas, stomach, and intestine. However, it remained
      unknown if this capability is active during anorectal development in the normal
      and anorectal malformations (ARM) rat embryos. MATERIALS AND METHODS: In this
      study, ethylenethiourea (ETU)-induced ARM model was introduced to investigate the
      expression pattern of Tcf4 during anorectal development using immunohistochemical
      staining, reverse transcriptase polymerase chain reaction (RT-PCR), and Western
      blot analysis. RESULTS: Immunostaining revealed that Tcf4 expression showed space
      dependent changes in the developing anorectum: in normal embryos, Tcf4 protein is
      initially expressed in the dorsal endoderm of urorectal septum (URS) and hindgut
      on embryonic day 13 (E13). Additionally, separate expression domain develops
      intensively on the dorsal CM on E14. On E15, positive cells are then detected in
      the fused tissue of URS, and prominently in the anal membrane. In the ARM
      embryos, however, the epithelium of the cloaca, URS, and anorectum was negative
      or faint for Tcf4. In Western blot and RT-PCR, time-dependent changes of Tcf4
      protein and mRNA expression were remarkable during the anorectal development: on
      E14, E14.5, and E15, the expression level reached the peak; after E16, Tcf4
      expression gradually decreased. In contrast, in ARM embryos, spatiotemporal
      expression of Tcf4 was imbalanced during the anorectal morphogenesis from E13 to
      E16. CONCLUSIONS: These data implied that the downregulation of Tcf4 at the time
      of cloacal separation into rectum and urethra might be related to the development
      of ARM.

PMID- 19387660
TI  - Risk factors of lateral pelvic lymph node metastasis in advanced rectal cancer.
AB  - BACKGROUND: To clarify the risk factors of lateral pelvic lymph node (LPLN)
      metastasis of rectal cancer, we examined associations between LPLN status and
      clinicopathological factors including LPLN status diagnosed by computed
      tomography (CT). METHODS: We reviewed a total of 210 patients with advanced
      rectal cancer, of which the lower margin was located at or below the peritoneal
      reflection, who underwent preoperative CT with 5-mm-thick sections and lateral
      pelvic lymph node dissection at the National Cancer Center Hospital between
      February 1998 and March 2006. RESULTS: Forty-seven patients (22.4%) had LPLN
      metastasis. Multivariate analysis showed that LPLN status diagnosed by CT,
      pathological regional lymph node status, tumor location, and tumor
      differentiation were significant risk factors for LPLN metastasis. Among 45
      patients with well-differentiated adenocarcinoma who were LPLN-negative and in
      whom CT had found no regional lymph node metastasis, none had LPLN metastasis. On
      the other hand, among 13 patients with moderate or less differentiated lower
      rectal adenocarcinoma who were LPLN-positive and in whom CT had revealed regional
      lymph node metastasis, 12 (92.3%) had LPLN metastasis. CONCLUSIONS: LPLN status
      diagnosed by CT, pathological regional LN status, tumor location, and tumor
      differentiation are significant risk factors for LPLN metastasis. Using these
      factors, patients can be classified as having a low or high risk of LPLN
      metastasis.

PMID- 19387661
TI  - Improved survival in an Asian cohort of young colorectal cancer patients: an
      analysis of 523 patients from a single institution.
AB  - BACKGROUND: Colorectal cancer (CRC) in the young is rare. Outcomes remain varied
      compared to older populations. The study reviews characteristics and overall
      survival (OS) of CRC in patients < or =50 years old. MATERIALS AND METHODS: Five
      hundred and twenty-three (14%) of 3,796 sporadic CRCs were identified. Patients
      were compared for demographics, tumour characteristics, treatment, and 5-year
      overall specific survival. Independent prognostic factors were evaluated.
      RESULTS: The majority were males (54%) with a median age of 45 years (range 19-50
      years). Sixty-three percent of the patients presented with advanced stage disease
      (stage III and IV), and tumours were predominantly left-sided (83%). A higher
      frequency of mucinous or signet ring cell histological subtypes (16% vs 9%, p =
      0.028) as well as poorly differentiated tumours (30% vs 12%, p = 0.0001) were
      present in younger patients < or =40 years. With a median follow-up of 41 months,
      the 5-year OS is 58% (95% confidence interval 53-64%). Younger patients < or =40
      years had significantly superior 5-year OS of 62% vs 58% in the age group 41-50
      years old (p = 0.004). Multivariate analysis identified five independent
      prognostic features: age group of 41-50 years, poorly differentiated tumour
      grade, presence of perineural infiltration, high tumour stage, and
      carcinoembryonic antigen values > or =5 ng/ml. CONCLUSION: This study has
      revealed significantly improved 5-year survival in young CRC compared to those
      reported in the literature.

PMID- 19387662
TI  - Lymphatic vessel invasion detected by monoclonal antibody D2-40 as a predictor of
      lymph node metastasis in T1 colorectal cancer.
AB  - OBJECTIVE: When selecting patients who are at high risk for lymph node
      metastasis, the detection of lymphatic vessel invasion (LVI) is important. We
      investigated LVI detected by D2-40 staining as a predictor of lymph node
      metastasis in T1 colorectal cancer. MATERIALS AND METHODS: Clinicopathological
      factors including LVI were investigated in 136 patients who underwent colectomy
      with lymph node dissection for T1 colorectal cancer. We used immunostaining with
      monoclonal antibody D2-40 to detect LVI. RESULTS: Lymph node metastases were
      found in 18 patients (13.2%), and LVI were detected in 45 (33%); lymph node
      metastasis was more frequently observed in LVI-positive groups (13/45 vs 5/91, p
      < 0.001). Both univariate and multivariate analyses revealed that LVI detected by
      D2-40 and a poorly differentiated histology at the invasion front were
      independent risk factors of lymph node metastasis. CONCLUSION: LVI detected by D2
      40 is important for the prediction of lymph node metastasis.

PMID- 19387663
TI  - Long-term result after rubber band ligation for haemorrhoids.
AB  - PURPOSE: Rubber band ligation (RBL) is a well-known and recognised outpatient
      procedure utilised for the treatment of symptomatic internal haemorrhoids. This
      paper describes a retrospective study which analyses the short- and long-term
      results of a personal series of patients. MATERIALS AND METHODS: A consecutive
      group of 206 patients with symptomatic internal second- and third-degree
      haemorrhoids were treated with RBL as outpatients from 1982 to 1989. Two or three
      piles were legated in a single session. All patients were systematically visited
      after 1 month and 1 year. Respectively after 10 and 17 years, all the patients
      were contacted to obtain a telephone follow-up. RESULTS: The short-term follow-up
      at 1 month and at 1 year showed that 46% of the patients experienced moderate
      anal pain for 24 h post procedure. Two patients had severe pain (1%) and were
      admitted in the hospital to be submitted to an operative haemorrhoidectomy within
      a few days. Only 2.4% of the patients experienced rectal bleeding after a week,
      and 20% had a second session of RBL after 1 month. At 1 year follow-up, 90% of
      the patients with second-degree piles and 75% of patients with third-degree piles
      reported no residual symptoms. The long-term telephone follow-up at 10 and 17
      years collected the history of 138 patients (67%). A group of 69% was
      asymptomatic, 28% had residual symptoms, and 3% needed further surgery.
      CONCLUSION: RBL is a safe and effective treatment for symptomatic internal
      haemorrhoids. Our long-term follow-up demonstrated good long-term results for
      internal second- and third-degree haemorrhoids.

PMID- 19387664
TI  - Multicentre review of lymph node harvest in colorectal cancer: are we
      understaging colorectal cancer patients?
AB  - BACKGROUND: Lymph node examination in colorectal cancer is of vital importance
      for accurate staging. Patients who have fewer nodes examined may be understaged
      and not offered adjuvant chemotherapy. The national institute of clinical
      excellence and the association of coloproctology of Great Britain and Ireland
      both recommend that 12 nodes should be examined for accurate staging. The aim of
      this study was to assess lymph node harvest at five hospitals in the northwest of
      England in respect to these guidelines. MATERIALS AND METHODS: This study is a
      retrospective review of all colorectal cancer resections over a 1-year period at
      five hospitals. RESULTS: Two hospitals met the national guidelines of a median of
      12 or more nodes. Overall, over 50% of colorectal cancers contained fewer than 12
      nodes. Fifty-three point seven percent (53.7%) of Dukes B patients did not have
      12 nodes in their specimens and may therefore be understaged. There was a
      significant variation between hospitals in terms of the number of cancers with 12
      or more nodes (P < 0.0001) and the number of Dukes B cancers with 12 or more
      nodes (P < 0.008). CONCLUSION: Over 50% of all colorectal cancer specimens
      contain fewer than 12 lymph nodes despite clear national guidelines. This is of
      particular importance to Dukes B cancers where over 53% of cases may be
      understaged and not offered adjuvant therapy. Significant variation exists
      between hospitals within the same region.

PMID- 19387665
TI  - [Lyme borreliosis].
AB  - Lyme borreliosis is a multi-system infectious disease that primarily affects the
      skin, nervous system, heart, and joints. It is caused by the tick-borne
      spirochete Borrelia burgdorferi sensu lato. Diagnosis is made on the basis of
      clinical symptoms and supported by a positive serology. Antibiotic therapy should
      be started immediately after the diagnosis has been established and is
      administered according to stage and symptoms of the disease. Doxycycline,
      amoxicillin, and ceftriaxone are the antibiotics of choice. Early Lyme disease is
      almost always cured by one antibiotic course that also prevents subsequent
      disease manifestations. After antibiotic therapy of late disease manifestations,
      symptoms resolve only slowly and remission is usually achieved after weeks or
      even months. Chronic or therapy-resistant disease courses and residual symptoms
      after therapy are rare.

PMID- 19387666
TI  - [Rheumapathology].

PMID- 19387668
TI  - Arthroscopic locking plate removal after proximal humeral fractures.
AB  - The incidence of proximal humeral fractures increases. The locking plate
      osteosynthesis is a standard procedure to treat displaced proximal humeral
      fractures. In the mostly affected elderly patients with an osteoporotic bone
      structure, complication rate is still high. An implant removal is commonly
      required. But also younger patients often request for hardware removal. The open
      implant removal with a subacromial and subdeltoideal arthrolysis is an extensive
      secondary surgery for the patients. We present a new technique to remove a
      locking plate from the proximal humerus arthroscopically with all advantages of
      the minimally invasive surgery, and the possibility to treat concomitant
      intraarticular pathologies parallelly.

PMID- 19387667
TI  - APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy.
AB  - Abeta accumulation has an important function in the etiology of Alzheimer's
      disease (AD) with its typical clinical symptoms, like memory impairment and
      changes in personality. However, the mode of this toxic activity is still a
      matter of scientific debate. We used the APP/PS1KI mouse model for AD, because it
      is the only model so far which develops 50% hippocampal CA1 neuron loss at the
      age of 1 year. Previously, we have shown that this model develops severe learning
      deficits occurring much earlier at the age of 6 months. This observation prompted
      us to study the anatomical and cellular basis at this time point in more detail.
      In the current report, we observed that at 6 months of age there is already a 33%
      CA1 neuron loss and an 18% atrophy of the hippocampus, together with a drastic
      reduction of long-term potentiation and disrupted paired pulse facilitation.
      Interestingly, at 4 months of age, there was no long-term potentiation deficit in
      CA1. This was accompanied by reduced levels of pre- and post-synaptic markers. We
      also observed that intraneuronal and total amount of different Abeta peptides
      including N-modified, fibrillar and oligomeric Abeta species increased and
      coincided well with CA1 neuron loss. Overall, these data provide the basis for
      the observed robust working memory deficits in this mouse model for AD at 6
      months of age.

PMID- 19387669
TI  - Arthroscopic operations in knee joint with early-stage tuberculosis.
AB  - INTRODUCTION: Due to atypical clinical presentation, wide use of antibiotics and
      lack of specificity in diagnosis, misdiagnosis is common, and diagnosis of
      tubercular infection in a joint is increasingly difficult. The use of arthroscopy
      for the diagnosis and treatment of early-stage knee TB has rarely been reported.
      Through this case series we describe the usefulness of arthroscopy for the
      management of synovial tuberculosis of the knee joint. MATERIALS AND METHODS:
      Synovectomy and synovial membrane biopsy were performed using arthroscopy in ten
      subjects suffering from synovial tuberculosis. This was combined with intra
      articular isoniazid injection and systemic antituberculosis drugs. RESULTS: In
      all cases, continuous passive motion exercise was started 2 days after operation
      and they were followed up from 6 months to 3 years. The flexion angles 90 degrees
      +/- 5 degrees preoperatively increased to 120 degrees +/- 14 degrees in nine
      patients following surgery, the extension limit angle also improved from an
      average 20 degrees +/- 3 degrees preoperatively to 5 degrees +/- 1 degrees
      postoperatively. There was a significant difference in knee function index
      between preoperation and postoperation (t = 6.9, t = 6.3, P < 0.01). Japanese
      Institute of Plastic Surgery synovial disease treatment success criteria was also
      improved from 44.4 +/- 8.4 points before surgery to 81.5 +/- 10.4 following
      surgery (t = 8.749, P < 0.01). The joint swelling disappeared or was relieved
      after 2 months. No relapse of tuberculosis was found at the time of follow-up.
      CONCLUSION: Combined use of arthroscopy and antituberculosis medication appears
      to be advantageous for the management of early-stage synovial tuberculosis of the
      knee joint. Arthroscopic removal of the pannus allows better nutrition of the
      cartilage and thus greatly improves the joint function.

PMID- 19387670
TI  - Joint-preserving surgical treatment of spontaneous osteonecrosis of the knee.
AB  - BACKGROUND: To date, reports of surgical treatment of spontaneous osteonecrosis
      of the knee (SPONK) refractory to non-operative treatment have primarily focused
      on knee arthroplasty. This report presents an overview of the characteristics of
      SPONK and reports our experience with joint-preserving surgical treatment of this
      condition. METHODS: Fifteen patients who had joint-preserving surgery after
      failed non-operative modalities were studied. These patients were treated at a
      single center between January 1998 and September 2006 with a combination of
      arthroscopy and core decompression, or osteochondral autograft transfers.
      RESULTS: Thirteen of the 15 knees (87%) had knee joint survival with a mean Knee
      Society Score of 81 points (range 45-100 points) at a mean follow-up of 40 months
      (range 9-120 months). Five of seven knees treated with core decompression had a
      successful clinical outcome. One of the patients who failed core decompression
      later underwent osteochondral autograft transfer, and eight of nine knees treated
      with this modality had a successful outcome. CONCLUSION: Overall, these results
      demonstrate that joint-preserving surgical treatment can successfully postpone
      the need for knee arthroplasty in selected patients with pre-collapse SPONK.

PMID- 19387671
TI  - Computer-assisted antetorsion control prevents malrotation in femoral nailing: an
      experimental study and preliminary clinical case series.
AB  - MATERIALS AND METHODS: The effect of fluoroscopy-based navigation for femoral
      fracture reduction on the prevention of malrotation was examined in an
      experimental setting followed by a first case series. Eleven cadaver femurs were
      used. All femurs were reduced by closed methods. An optoelectronic navigation
      system was utilized to check for fragment reduction and alignment. Fluoroscopic
      control without navigation was used as the control group. The Six Sigma Analysis
      [offset capability index (C (pk)) = 1.3] was used to compare the probability of
      outliers of more than 15 degrees . In the clinical case series the same
      navigation tool was used in ten non-consecutive patients with femoral fractures.
      Torsional differences between both legs were measured postoperatively by CT scan.
      RESULTS: The highest malrotation in the navigated group was 7.0 degrees for the
      cadaver testings, while two femurs in the control group showed a difference of
      more than 10 degrees (10.3 degrees , 17.4 degrees). Only the navigated group
      showed a sufficient offset capability index (C (pk-navigated) = 1.83; C (pk
      conventional) = 0.59). In the clinical series nine femurs were successfully
      reduced by navigation control. The average malrotation was 6.6 degrees . No
      patient had a torsional difference of more than 10 degrees. CONCLUSION: Navigated
      femoral nailing reduces the risk for outliers of postoperative torsional
      differences and might avoid revision surgery for malrotation. LEVEL OF EVIDENCE:
      IV.

PMID- 19387672
TI  - Prevalence and significance of human parvovirus variants in skin from primary
      cutaneous T cell lymphomas, inflammatory dermatoses and healthy subjects.
AB  - Primary cutaneous T cell lymphomas (CTCL) represent a heterogeneous group of T
      lymphomas. Virus involvement in CTCL pathogenesis has been extensively
      investigated, but no data are available as to a causative role of parvovirus B19.
      The prevalence of parvovirus variants (B19, LaL1/K71, V9) was investigated by
      using two nested PCRs and a genotype-2 semiquantitative PCR (Q-PCR). Parvovirus
      DNA was detected in similar percentage in healthy skin controls (40%; n = 42),
      inflammatory dermatoses (ID) (41%; n = 80) and CTCL (34%; n = 76). Among
      variants, genotype-2 was more prevalent in ID (26%) and CTCL (22%) than in normal
      skin (14%; p < 0.05). genotype-3 was never found in normal skin and was rare in
      ID. The only four pathological skin samples with a quantifiable genome copies/mug
      DNA values in Q-PCR were ID. In conclusion, despite the skin represent a
      reservoir for genotype-1, parvovirus infection is not involved in the
      etiopathogenesis of CTCL.

PMID- 19387673
TI  - Diagnostic property of cervical phosphorylated insulin-like growth factor binding
      protein-1 in the prediction of preterm labor in symptomatic patients.

PMID- 19387674
TI  - Fetal demise by umbilical cord around abdomen and stricture.
AB  - Umbilical cord abnormalities are accepted as conditions associated with
      intrauterine fetal demise (IUFD), and umbilical cord stricture is most frequently
      encountered. In addition, although cord entanglement with multiple loops rarely
      increases the perinatal mortality, it is associated with a significant increase
      in variable kind of morbidity such as growth restriction. We describe a 27-year
      old woman, with a missed abortion history at about 10 weeks' gestation in her
      first pregnancy, who presented to our outpatient department at 34 4/7 weeks of
      gestation due to decreased fetal activity during the preceding week. No fetal
      heart activity and blood flow had been detected by ultrasonography and pulsed
      wave Doppler. A demised fetus with umbilical cord stricture and three loops
      around abdomen was delivered and was weighted 1,830 g that was below the tenth
      percentile for the gestational age. Either umbilical cord stricture or
      entanglement around the body can affect the development of the fetus and even be
      lethal. The former might play a more important role in this case. Their etiology
      and the sequence of the events are still undetermined, and additional evaluation
      such as autopsy and further research may be needed. In addition, counsel and
      frequent fetal surveillance should be done in patients with previous IUFD
      attributed to cord stricture during next pregnancy because of undetermined risk
      of recurrence.

PMID- 19387675
TI  - An intravaginal carcinoma tissue in a patient with ovarian tumor.

PMID- 19387676
TI  - Puerperal group A Streptococcus infection.
AB  - Group A Streptococci infection during antenatal period as well as postnally can
      be very serious and would require intense management-both surgical and medical.
      Many authors believe the incidence is rising. High index of clinical suspicion is
      necessary in order to early intervention.

PMID- 19387677
TI  - The ciliary beat frequency of middle ear mucosa in children with chronic
      secretory otitis media.
AB  - The chronic secretory otitis media (CSOM) is a common disease in children. Its
      cardinal symptoms are recurrent middle ear effusions and conductive hearing loss.
      Until today, the pathophysiological mechanism of this disease remains unknown.
      The correlation with adenoids and tubal dysfunction during childhood seems to be
      obvious, but the origin of middle ear effusions still has to be clarified. It is
      known that the CSOM affects the mucociliary system in several ways. In order to
      find out more about these correlations, the ciliary beat frequency was examined
      in 123 samples of infantile middle ear mucosa suffering from CSOM. Samples were
      surveyed using a stroboscopic microscopy method. The results of this study showed
      a significant decrease of ciliary beat frequency (CBF) to an average of 7.4 s(-1)
      in children with a CSOM. The healthy group of control showed a frequency of 10.1
      s(-1). The measured CBF dataset was correlated with microbiological findings. We
      found a typical bacterial profile in nearly all the cases that were examined but
      were unable to find a specific bacterium decreasing CBF. This study provides
      evidence for the diminution of CBF in cases of CSOM in comparison to a healthy
      control group. Our findings emphasize the importance of stopping the vicious
      circle of recurrent effusions by paracentesis or grommet insertion.

PMID- 19387678
TI  - Pseudohypacusis: the most frequent etiology of sudden hearing loss in children.
AB  - Sudden hearing loss is a rare pathology in children. Several factors may be
      responsible for it although the exact etiology remains frequently undiagnosed.
      Among them, pseudohypacusis has been reported. However, the extent to which this
      pathology contributes to sudden hearing loss in children is unknown. This study
      evaluates the incidence of pseudohypacusis in children presented with sudden
      hearing loss. The medical records of 48 children presented to our department
      because of sudden hearing loss from 2002 to 2007 were reviewed. Diagnostic
      process included both subjective and objective audiological tests while organic
      hearing losses were further subjected to proper evaluation and treatment. 26
      cases (54%) of pseudohypacusis and 22 cases (46%) of organic sudden hearing loss
      were diagnosed. In the pseudohypacustic group, girls outnumbered boys (16:10) and
      their mean age was 10.5 years. Pseudohypacusis represents the most frequent
      etiology of sudden hearing loss in children. Its detection is relatively simple
      using conventional audiological tests though in some cases even experienced
      clinicians may come to incorrect diagnosis.

PMID- 19387679
TI  - An effective surgical technique for the excision of first branchial cleft
      fistula: make-inside-exposed method by tract incision.
AB  - The objective of the study was to evaluate the effectiveness of make-inside
      exposed method by tract incision to remove the first branchial cleft fistula,
      while avoiding injury to the facial nerve and completely excising the fistula.
      Fifteen patients who underwent the make-inside-exposed method by tract incision
      for excision of the first branchial cleft anomalies were reviewed. Pre-auricular
      fistulas or sinuses occurred in nine of them, and post-auricular fistulas
      occurred in six cases. The symptoms of these patients, post-operative
      complications including facial nerve paralysis and recurrence of the lesion, were
      observed. Of the 15 patients, 6 had undergone previous incision and drainage of
      abscess for the infected fistulas. All patients had swelling or suppuration in
      the pre-auricular or post-auricular region. Post-auricular fistulas had intimate
      relationship with facial nerves in most of the cases (5/6). The fistulas or
      sinuses tracts were all removed completely without any complications, such as
      facial palsy, but severe scar formation occurred in one case. No remnant of
      fistula or sinus was observed during the follow-up period from 2 to 12 years
      postoperatively. Make-inside-exposed method by tract incision is an effective and
      safe technique for the excision of the first branchial cleft fistula. The two
      main advantages of this method are that it can preserve the facial nerve safely
      and excise the fistulas completely. However, skillful microsurgery manipulation
      is necessary.

PMID- 19387680
TI  - The expression of receptivity markers in the fallopian tube epithelium.
AB  - Pinopodes represent the morphological and integrins, the biomolecular markers of
      endometrial receptivity. We studied using scanning electron microscopy, the
      expression of pinopodes on tubal samples and their corresponding endometria, from
      21 women of reproductive age (7 from proliferative phase, 7 from day LH +5 and 7
      from day LH +7). In addition, we examined the immunohistochemical staining of
      integrins alpha v beta 3, alpha v beta 5 and their ligands, fibronectin (FN) and
      osteopontin (OPN) in the same tubal epithelium samples. Pinopodes were detected
      on the tubal epithelium exclusively during day LH +7, coincident with their
      formation in the endometrium and synchronous to alpha v beta 3 sharp increase in
      the oviduct epithelium, suggesting a regulation similar to the endometrium. In
      contrast, alpha v beta 5, FN and OPN remained unchanged during the cycle. These
      results show for the first time the formation of pinopodes in the tubal
      epithelium at the time of endometrial receptivity and correlate it with the
      upregulation of the intact dimmer alpha v beta 3 in the tubes.

PMID- 19387681
TI  - Reciprocal amplification of ROS and Ca(2+) signals in stressed mdx dystrophic
      skeletal muscle fibers.
AB  - Muscular dystrophies are among the most severe inherited muscle diseases. The
      genetic defect is a mutation in the gene for dystrophin, a cytoskeletal protein
      which protects muscle cells from mechanical damage. Mechanical stress, applied as
      osmotic shock, elicits an abnormal surge of Ca(2+) spark-like events in skeletal
      muscle fibers from dystrophin deficient (mdx) mice. Previous studies suggested a
      link between changes in the intracellular redox environment and appearance of
      Ca(2+) sparks in normal mammalian skeletal muscle. Here, we tested whether the
      exaggerated Ca(2+) responses in mdx fibers are related to oxidative stress.
      Localized intracellular and mitochondrial Ca(2+) transients, as well as ROS
      production, were assessed with confocal microscopy. The rate of basal cellular
      but not mitochondrial ROS generation was significantly higher in mdx cells. This
      difference was abolished by pre-incubation of mdx fibers with an inhibitor of
      NAD(P)H oxidase. In addition, immunoblotting showed a significantly stronger
      expression of NAD(P)H oxidase in mdx muscle, suggesting a major contribution of
      this enzyme to oxidative stress in mdx fibers. Osmotic shock produced an abnormal
      and persistent Ca(2+) spark activity, which was suppressed by ROS-reducing agents
      and by inhibitors of NAD(P)H oxidase. These Ca(2+) signals resulted in
      mitochondrial Ca(2+) accumulation in mdx fibers and an additional boost in
      cellular and mitochondrial ROS production. Taken together, our results indicate
      that the excessive ROS production and the simultaneous activation of abnormal
      Ca(2+) signals amplify each other, finally culminating in a vicious cycle of
      damaging events, which may contribute to the abnormal stress sensitivity in
      dystrophic skeletal muscle.

PMID- 19387683
TI  - Extranodular background liver parenchyma of focal nodular hyperplasia:
      histopathological characteristics.
AB  - Focal nodular hyperplasia (FNH) of the liver is considered to develop as a
      hyperplastic response to a preexisting vascular abnormality. From the pathogenic
      point of view, we studied histological alterations in the extranodular background
      liver tissue of FNH (FNH-bg-liver). We compared ten FNH-bg-livers with ten non
      FNH cases (non-FNH-liver) and found small uniform nodule formations with ring
      like siderosis in the FNH-bg-livers (4/7, 57%) but not in the non-FNH-livers.
      Abnormal small arteries not accompanied by portal tracts were observed in six of
      six FNH-bg-livers for which immunohistochemical study was available, while this
      was observed in only three of the ten non-FNH-livers. CD34-positive sinusoids
      around the portal tracts were observed in only the FNH-bg-livers (3/6, 50%).
      Further, two of ten FNH-bg-livers had ectopic pancreatic tissue. Ring-like
      siderosis, abnormal small arteries, CD34-positive sinusoids, and ectopic
      pancreatic tissue were characteristic in the extranodular background liver tissue
      in cases of FNH.

PMID- 19387682
TI  - Claudins 1, 3, and 4 protein expression in ER negative breast cancer correlates
      with markers of the basal phenotype.
AB  - In the present study we investigated the protein expression of claudins 1, 3, and
      4 and their relationship to clinical variables and outcome in a cohort of ER-ve
      and ER+ve human invasive breast cancers. Immunohistochemical analysis was
      performed on tissue microarrays representing a total of 412 tumors and
      interpretable data was derived from 314, 299, and 306 tumors for claudins 1, 3,
      and 4, respectively. In the ER+ve subset, 5%, 89%, and 52%, and in the ER-ve
      subset, 39%, 79%, and 79% of tumors stained positively for claudins 1, 3, and 4,
      respectively (p < 0.0001, p = 0.026, p < 0.0001). Thus, in the two subsets, a
      significantly higher number of tumors were positive for claudins 3 and 4,
      compared to claudin 1. In addition, protein expressions of claudins 1 and 4 were
      significantly higher in those tumors that displayed characteristics of the basal
      like subtype of breast cancers (ER-ve, Her-2-ve, EGFR+ve, CK5/6+ve). This study
      shows a unique pattern of expression for the different claudins in ER-ve and
      ER+ve tumors. Our data also suggests that increased expression of claudins 1 and
      4 was associated with the basal-like subtype of breast cancers, a subtype
      generally linked to poor outcome.

PMID- 19387684
TI  - Does echocardiography facilitate determination of hemodynamic significance
      attributable to the ductus arteriosus?
AB  - INTRODUCTION: The assignment of hemodynamic significance to a patent ductus
      remains a challenge for neonatal intensivists. The impact is medical uncertainty
      and ongoing debate as to when treatment should be provided if ever. DISCUSSION:
      Patent ductus arteriosus is associated with significant neonatal morbidities
      including necrotizing enterocolitis and brain injury; causality has not been
      proven. In addition, there are limited data suggesting a beneficial effect of
      therapeutic intervention. The inability to accurately differentiate the
      pathological ductus arteriosus from the innocent ductus arteriosus may
      contribute, in part, to the lack of scientific evidence of benefit or causality.
      Our group has previously proposed the need for a staging system to characterize
      the clinical and echocardiography impact of the ductus arteriosus. This approach
      requires comprehensive echocardiography evaluation to assess ductal size and the
      degree of pulmonary overcirculation/systemic hypoperfusion related to the
      transductal shunt. CONCLUSION: In this review, we will highlight the evidence for
      echocardiography markers of hemodynamic significance and speculate as to how they
      may facilitate improved decision making in the neonatal intensive care unit.

PMID- 19387685
TI  - Expression of hepcidin and other iron-regulatory genes in human hepatocellular
      carcinoma and its clinical implications.
AB  - PURPOSE: We aimed to assess expression of ten iron-regulatory genes in
      hepatocellular carcinoma (HCC) and its clinical implications. METHODS: We used
      real-time polymerase chain reaction to measure ten iron-regulatory genes' mRNA
      and Perls' stain to assess iron stores in 50 HCCs and adjacent nontumor
      specimens. We compared the differences of gene expression and iron stores between
      tumor and nontumor specimens, and analyzed the relationships of gene expression
      with hepatic iron stores, patients' hemoglobin levels and clinicopathologic
      parameters. RESULTS: Hepcidin, ceruloplasmin, transferrin, and transferrin
      receptor 2 were downregulated, while transferrin receptor 1 was upregulated in
      HCC. Hepcidin was markedly decreased in HCC but still correlated with hepatic
      iron stores. Iron-regulatory genes varied in their relationships of expression
      with clinicopathologic parameters. CONCLUSIONS: Altered expression of iron
      regulatory genes in HCC may disturb patient's iron balance. Hepcidin may play a
      role in defending the body against HCC.

PMID- 19387686
TI  - Model structure of the immunodominant surface antigen of Eimeria tenella
      identified as a target for sporozoite-neutralizing monoclonal antibody.
AB  - Eimeria tenella is a coccidian parasite of great economical importance for
      poultry industry. The surface of Eimeria invasive agents, sporozoites and
      merozoites, is coated with a family of developmentally regulated
      glycosylphosphatidylinositol (GPI)-linked surface antigens (SAGs), some of them
      involved in the initiation of the infection process. Using 2D gel electrophoresis
      followed by mass spectrometry, an antigenic surface protein EtSAG1 (TA4) of E.
      tenella sporozoites has been identified as a target of neutralizing monoclonal
      antibody 2H10E3. To clarify the mechanism of invasion inhibition caused by the
      EtSAG1-specific antibodies, a structural model of EtSAG1 was generated. It
      appears that "EtSAG fold" does not bear an evolutionary relationship to any known
      protein structure. The intra- and interchain disulfide bonds could be assigned to
      certain pairs of six conserved cysteines found in members of the EtSAG protein
      family. The outward-facing surface of the antigen was found to comprise an
      expanded positively charged patch, thus suggesting that the parasite invasion
      process may be initiated by sporozoite attachment to negatively charged sulfated
      proteoglycans on the surface of the host cell.

PMID- 19387687
TI  - Physiological response of bovine subcommissural organ to endothelin 1 and
      bradykinin.
AB  - The circumventricular organs (CVOs) regulate certain vegetative functions.
      Receptors for bradykinin (BDK) and endothelin (ET) have been found in some CVOs.
      The subcommissural organ (SCO) is a CVO expressing BDK-B2 receptors and secreting
      Reissner's fiber (RF) glycoproteins into the cerebrospinal fluid. This
      investigation was designed to search for ET receptors in the bovine SCO and, if
      found, to study the functional properties of this ET receptor and the BDK-B2
      receptor. Cryostat sections exposed to (125)I ET1 showed dense labeling of
      secretory SCO cells, whereas the adjacent ciliated ependyma was devoid of
      radiolabel. The binding of (125)I ET1 was abolished by antagonists of ETA and ETB
      receptors. The intracellular calcium concentration ([Ca(2+)](i)) was measured in
      individual SCO cells prior to and after exposure to ET1, BDK, or RF
      glycoproteins. ET1 (100 nM) or BDK (100 nM) caused an increase in [Ca(2+)](i) in
      48% or 53% of the analyzed SCO-cells, respectively. RF glycoproteins had no
      effect on [Ca(2+)](i) in SCO cells. ET and BDK evoked two types of calcium
      responses: prolonged and short responses. Prolonged responses included those with
      a constant slow decline of [Ca(2+)](i), biphasic responses, and responses with a
      plateau phase at the peak level of [Ca(2+)](i). ET1-treated SCO explants
      contained a reduced amount of intracytoplasmic AFRU (antiserum to RF
      glycoproteins)-immunoreactive material compared with sham-treated control
      explants. Our data suggest that ET1 and BDK regulate [Ca(2+)](i) in bovine SCO
      cells, and that the changes in [Ca(2+)](i) influence the secretory activity of
      these cells.

PMID- 19387688
TI  - Role of neurotrophin signalling in the differentiation of neurons from dorsal
      root ganglia and sympathetic ganglia.
AB  - Manipulation of neurotrophin (NT) signalling by administration or depletion of
      NTs, by transgenic overexpression or by deletion of genes coding for NTs and
      their receptors has demonstrated the importance of NT signalling for the survival
      and differentiation of neurons in sympathetic and dorsal root ganglia (DRG).
      Combination with mutation of the proapoptotic Bax gene allows the separation of
      survival and differentiation effects. These studies together with cell culture
      analysis suggest that NT signalling directly regulates the differentiation of
      neuron subpopulations and their integration into neural networks. The high
      affinity NT receptors trkA, trkB and trkC are restricted to subpopulations of
      mature neurons, whereas their expression at early developmental stages largely
      overlaps. trkC is expressed throughout sympathetic ganglia and DRG early after
      ganglion formation but becomes restricted to small neuron subpopulations during
      embryogenesis when trkA is turned on. The temporal relationship between trkA and
      trkC expression is conserved between sympathetic ganglia and DRG. In DRG, NGF
      signalling is required not only for survival, but also for the differentiation of
      nociceptors. Expression of neuropeptides calcitonin gene-related peptide and
      substance P, which specify peptidergic nociceptors, depends on nerve growth
      factor (NGF) signalling. ret expression indicative of non-peptidergic nociceptors
      is also promoted by the NGF-signalling pathway. Regulation of TRP channels by NGF
      signalling might specify the temperature sensitivity of afferent neurons
      embryonically. The manipulation of NGF levels "tunes" heat sensitivity in
      nociceptors at postnatal and adult stages. Brain-derived neurotrophic factor
      signalling is required for subpopulations of DRG neurons that are not fully
      characterized; it affects mechanical sensitivity in slowly adapting, low
      threshold mechanoreceptors and might involve the regulation of DEG/ENaC ion
      channels. NT3 signalling is required for the generation and survival of various
      DRG neuron classes, in particular proprioceptors. Its importance for peripheral
      projections and central connectivity of proprioceptors demonstrates the
      significance of NT signalling for integrating responsive neurons in neural
      networks. The molecular targets of NT3 signalling in proprioceptor
      differentiation remain to be characterized. In sympathetic ganglia, NGF
      signalling regulates dendritic development and axonal projections. Its role in
      the specification of other neuronal properties is less well analysed. In vitro
      analysis suggests the involvement of NT signalling in the choice between the
      noradrenergic and cholinergic transmitter phenotype, in the expression of various
      classes of ion channels and for target connectivity. In vivo analysis is required
      to show the degree to which NT signalling regulates these sympathetic neuron
      properties in developing embryos and postnatally.

PMID- 19387689
TI  - The effect of rhGH on height velocity and BMI in children with CKD: a report of
      the NAPRTCS registry.
AB  - The aim of this investigation was to evaluate the impact of recombinant human
      growth hormone (rhGH) therapy on height velocity (HV), estimated glomerular
      filtration rate (eGFR) and body mass index (BMI) in a large cohort of children
      with chronic kidney disease (CKD). We reviewed longitudinal data from patients
      enrolled in the chronic renal insufficiency registry of the North American
      Pediatric Renal Trials and Collaborative Studies (NAPRTCS). Of the 7189 patients
      enrolled in the registry, 827 (11.5%) received rhGH. A total of 787 children with
      CKD previously rhGH naive who received rhGH for 1-4 years (median 1.5 years) were
      paired with 787 control patients, and over 100 of the case-controls were followed
      for 4 years. The control group was matched for age, gender, height and length of
      time in the NAPRTCS registry. Height velocity was also compared to the general
      U.S. population. The eGFR of the treated group (37.5 ml/min per 1.73 m(2)) was
      significantly less than that of the control group (42.3 ml/min per 1.73 m(2); p <
      0.001). The rhGH-treated group had a significantly greater HV standard deviation
      score (SDS) than the control group (p < 0.01) at each 6-months post-rhGH
      treatment initiation point for 2.5 years (p < 0.007). Among 220 pairs at 2 years,
      the height SDS of the rhGH group was 0.56 SDS higher than that of the control
      group (p < 0.05). Treatment with rhGH had no significant impact on the BMI or
      eGFR. As demonstrated in smaller cohorts, rhGH usage is associated with improved
      HV in children with CKD. In contrast, rhGH does not appear to have any impact on
      BMI or kidney function in this population of patients.

PMID- 19387690
TI  - [A new look at chronic pain].

PMID- 19387691
TI  - [Symptom and complaint validation of chronic pain in social medical evaluation.
      Part I: Terminological and methodological approaches].
AB  - Chronic pain accompanied by disability and handicap is a frequent symptom
      necessitating medical assessment. Current guidelines for the assessment of
      malingering suggest discrimination between explanatory demonstration, aggravation
      and simulation. However, this distinction has not clearly been put into operation
      and validated. The necessity of assessment strategies based on general principles
      of psychological assessment and testing is emphasized. Standardized and
      normalized psychological assessment methods and symptom validation techniques
      should be used in the assessment of subjects with chronic pain problems. An
      adaptive procedure for assessing the validity of complaints is suggested to
      minimize effort and costs.

PMID- 19387692
TI  - Solar radiation transmission in and around canopy gaps in an uneven-aged
      Nothofagus betuloides forest.
AB  - The transmission of direct, diffuse and global solar radiation in and around
      canopy gaps occurring in an uneven-aged, evergreen Nothofagus betuloides forest
      during the growing season (October 2006-March 2007) was estimated by means of
      hemispherical photographs. The transmission of solar radiation into the forest
      was affected not only by a high level of horizontal and vertical heterogeneity of
      the forest canopy, but also by low angles of the sun's path. The below-canopy
      direct solar radiation appeared to be variable in space and time. On average, the
      highest amount of transmitted direct solar radiation was estimated below the
      undisturbed canopy at the southeast of the gap centre. The transmitted diffuse
      and global solar radiation above the forest floor exhibited lower variability
      and, on average, both were higher at the centre of the canopy gaps. Canopy
      structure and stand parameters were also measured to explain the variation in the
      below-canopy solar radiation in the forest. The model that best fit the
      transmitted below-canopy direct solar radiation was a growth model, using plant
      area index with an ellipsoidal angle distribution as the independent variable (R
      (2) = 0.263). Both diffuse and global solar radiation were very sensitive to
      canopy openness, and for both cases a quadratic model provided the best fit for
      these data (R (2) = 0.963 and 0.833, respectively). As much as 75% and 73% of the
      variation in the diffuse and global solar radiation, respectively, were explained
      by a combination of stand parameters, namely basal area, crown projection, crown
      volume, stem volume, and average equivalent crown radius.

PMID- 19387693
TI  - Development of indicators for patient-centred cancer care.
AB  - PURPOSE: Assessment of current practice with a valid set of indicators is the key
      to successfully improving the quality of patient-centred care. For improvement
      purposes, we developed indicators of patient-centred cancer care and tested them
      on a population of patients with non-small cell lung cancer (NSCLC). METHODS:
      Recommendations for patient-centred care were extracted from clinical guidelines,
      and patients were interviewed to develop indicators for assessing the patient
      centredness of cancer care. These indicators were tested with regard to
      psychometric characteristics (room for improvement, applicability, discriminating
      capacity and reliability) on 132 patients with NSCLC treated in six hospitals in
      the east Netherlands. Data were collected from patients by means of
      questionnaires. RESULTS: Eight domains of patient-centred cancer care were
      extracted from 61 oncology guidelines and 37 patient interviews and were
      translated into 56 indicators. The practice test amongst patients with NSCLC
      showed the most room for improvement within the domains 'emotional and
      psychosocial support', 'physical support' and 'information supply'. Overall, 26
      of the 56 indicators had good psychometric characteristics. CONCLUSIONS:
      Developing a valid set of patient-centred indicators is a first step towards
      improving the patient centredness of cancer care. Indicators can be based on
      recommendations from guidelines, but adding patient opinions leads to a more
      complete picture of patient centredness. The practice test on patients with NSCLC
      showed that the patient centredness of cancer care can be improved. Our set of
      indicators may also be useful for future quality assessments for other patients
      with cancers or chronic diseases.

PMID- 19387694
TI  - Oral mucositis in patients receiving reduced-intensity regimens for allogeneic
      hematopoietic cell transplantation: comparison with conventional regimen.
AB  - GOALS OF WORK: Severe oral mucositis induced by allogeneic hematopoietic cell
      transplantation (HCT) is associated with intolerable pain and risk of systemic
      bacteremia infection. Differences between conventional HCT and reduced-intensity
      regimens for allogeneic HCT (RIST) may influence the occurrence and severity of
      oral mucositis. Here, we evaluated oral mucositis in patients undergoing RIST and
      compared the results with those in conventional allogeneic HCT patients to
      facilitate predictive measures for mucositis. PATIENTS AND METHODS: A total of
      127 consecutive patients undergoing HCT (conventional, 63; RIST, 64) were
      included in this study. Severity of oral mucositis during HCT period was
      evaluated daily. Differences in severity of mucositis among HCT types were
      analyzed. Use of morphine to control pain due to oral mucositis was evaluated in
      each HCT method. MAIN RESULTS: The severity of oral mucositis was reduced in
      patients undergoing RIST. Worsening of oral mucositis was delayed in patients
      receiving RIST. Use of morphine to control pain due to oral mucositis was
      significantly decreased in patients undergoing RIST compared with those receiving
      conventional allogeneic HCT. CONCLUSIONS: The severity of oral mucositis was
      reduced and the peak day of oral mucositis was delayed in RIST patients compared
      with those receiving conventional HCT.

PMID- 19387695
TI  - Oral moxifloxacin for outpatient treatment of low-risk, febrile neutropenic
      patients.
AB  - OBJECTIVES: Low-risk febrile neutropenic patients can be treated without
      hospitalization with oral antibiotic regimens. Combination regimens are
      recommended. Our objective was to evaluate the feasibility of quinolone
      monotherapy (moxifloxacin) in this setting. METHODS: In this open-label pilot
      study, eligible low-risk febrile neutropenic patients identified using pre
      defined criteria (MASCC Risk Index) received oral moxifloxacin (400 mg) in our
      emergency center and were discharged after a 4-8 h observation period to ensure
      clinical stability. They subsequently received moxifloxacin 400 mg daily as
      outpatients. Success of monotherapy, outpatient management, the development of
      adverse events, and major medical complications were recorded. RESULTS: The trial
      was closed without reaching the target sample size of 40 patients due to slow
      accrual. Twenty-one evaluable patients were enrolled, with sarcoma and breast
      cancer being the predominant underlying neoplasms. Most patients (76%) were
      severely neutropenic (</=100 cells/mm(3)) on enrollment. There were 13 episodes
      (62%) of unexplained fever and eight documented infections including five
      episodes (24%) of bacteremia. The overall success rate of monotherapy was 95%.
      One patient with unexplained fever and persistent neutropenia required
      hospitalization and responded to alternative therapy. No significant toxicity or
      severe medical complications occurred. CONCLUSIONS: Oral outpatient quinolone
      monotherapy for low-risk febrile neutropenic patients appears feasible and needs
      to be formally evaluated in large randomized clinical trials.

PMID- 19387696
TI  - Outcomes of C1 and C2 posterior screw fixation for upper cervical spine fusion.
AB  - To achieve stable fixation of the upper cervical spine in posterior fusions, the
      occiput is often included. With the newer techniques, excluding fixation to the
      occiput will retain the occiput-cervical motion, while still allowing a stable
      fixation. Harms's technique has been adapted at our institution and its
      effectiveness for indications such as C2 complex fractures and tumors using C1 or
      C2 as endpoints of a posterior fixation are reviewed. Fourteen cases were
      identified, consisting of one os odontoideum; four acute fractures and four non
      unions of the odontoid; three tumors and two complex fractures of C2 vertebral
      body, and one C2-C3 post-traumatic instability. One misplaced screw without
      clinical consequences was the only complication recorded. Screw loosening or
      migration was not observed at follow-up, showing a stable fixation.

PMID- 19387697
TI  - Does Wallis implant reduce adjacent segment degeneration above lumbosacral
      instrumented fusion?
AB  - Delayed complications following lumbar spine fusion may occur amongst which is
      adjacent segment degeneration (ASD). Although interspinous implants have been
      successfully used in spinal stenosis to authors' knowledge such implants have not
      been previously used to reduce ASD in instrumented lumbar fusion. This
      prospective controlled study was designed to investigate if the implantation of
      an interspinous implant cephalad to short lumbar and lumbosacral instrumented
      fusion could eliminate the incidence of ASD and subsequently the related re
      operation rate. Groups W and C enrolled initially each 25 consecutive selected
      patients. Group W included patients, who received the Wallis interspinous implant
      in the unfused vertebral segment cephalad to instrumentation and the group C
      selected age-, diagnosis-, level-, and instrumentation-matched to W group
      patients without interspinous implant (controls). The inclusion criterion for
      Wallis implantation was UCLA arthritic grade <II, while the exclusion criteria
      were previous lumbar surgery, severe osteoporosis or degeneration >UCLA grade II
      in the adjacent two segments cephalad to instrumentation. All patients suffered
      from symptomatic spinal stenosis and underwent decompression and 2-4 levels
      stabilization with rigid pedicle screw fixation and posterolateral fusion by a
      single surgeon. Lumbar lordosis, disc height (DH), segmental range of motion
      (ROM), and percent olisthesis in the adjacent two cephalad to instrumentation
      segments were measured preoperatively, and postoperatively until the final
      evaluation. VAS, SF-36, and Oswestry Disability Index (ODI) were used. One
      patient of group W developed pseudarthrosis: two patients of group C deep
      infection and one patient of group C ASD in the segment below instrumentation and
      were excluded from the final evaluation. Thus, 24 patients of group W and 21 in
      group C aged 65+ 13 and 64+ 11 years, respectively were included in the final
      analysis. The follow-up averaged 60 +/- 6 months. The instrumented levels
      averaged 2.5 + 1 vertebra for both groups. All 45 spines showed radiological
      fusion 8-12 months postoperatively. Lumbar lordosis did not change
      postoperatively. Postoperatively at the first cephalad adjacent segment: DH
      increased in the group W (P = 0.042); ROM significantly increased only in group C
      (ANOVA, P < 0.02); olisthesis decreased both in flexion (P = 0.0024) and
      extension (P = 0.012) in group W. The degeneration or deterioration of already
      existed ASD in the two cephalad segments was shown in 1 (4.1%) and 6 (28.6%)
      spines in W and C groups, respectively. Physical function (SF-36) and ODI
      improved postoperatively (P < 0.001), but in favour of the patients of group W (P
      < 0.05) at the final evaluation. Symptomatic ASD required surgical intervention
      was in 3 (14%) patients of group C and none in group W. ASD remains a significant
      problem and accounts for a big portion of revision surgery following instrumented
      lumbar fusion. In this series, the Wallis interspinous implant changed the
      natural history of ASD and saved the two cephalad adjacent unfused vertebra from
      fusion, while it lowered the radiographic ASD incidence until to 5 years
      postoperatively. Longer prospective randomized studies are necessary to prove the
      beneficial effect of the interspinous implant cephalad and caudal to instrumented
      fusion. We recommend Wallis device for UCLA degeneration I and II.

PMID- 19387698
TI  - Two-year results of interspinous spacer (X-Stop) implantation in 175 patients
      with neurologic intermittent claudication due to lumbar spinal stenosis.
AB  - The clinical outcome of patients with symptomatic lumbar spinal stenosis (LSS)
      was assessed during a follow-up period of 2 years after X-Stop implantation. The
      X-Stop is the most commonly used interspinous distraction device in patients with
      neurogenic intermittent claudication due to LSS. Between 2003 and 2007, more than
      1,000 patients were examined in our centre with symptoms of intermittent
      claudication due to spinal stenosis. Between February 2003 and June 2007, in 175
      of these patients an X-Stop device was implanted in one or two levels. Patients
      were clinically evaluated regularly during a follow-up period of up to 4 years
      using the VAS (leg pain) score and the Oswestry disability index. The mean VAS
      (leg pain) score in these 175 patients was reduced from 61.2% preoperatively to
      39.0% at the first clinical follow-up examination at 6 weeks postoperatively. The
      mean VAS score at 24 months postoperatively was 39.0%. Oswestry score was 32.6%
      preoperatively, 22.7% at 6 weeks, and 20.3% at 24 months postoperatively on
      average. In eight out of the implanted 175 patients, the X-Stop had to be removed
      and a microsurgical decompression had to be performed because of unsatisfactory
      effect of the interspinous distraction device. Our single-centre results indicate
      not only a satisfactory short-term, but also a good long-term effect during a
      follow-up period of 2 years. Functional MRI examinations provide helpful,
      positional-dependent preoperative information. More than any radiological
      feature, the typical clinical picture of positional-dependent claudication with a
      relief of symptoms during flexion is the most important factor for appropriate
      patient selection. The interspinous device does not replace microsurgical
      decompression in patients with massive stenosis and continuous claudication, but
      offers a save, effective and less invasive alternative in selected patients with
      spinal stenosis. Concerning the operative technique, a minimally invasive
      implantation with preservation of the interspinous ligament is appropriate.
      Functional (upright-) MRI examinations were able to demonstrate the positional
      dependent stenosis. If available, fMRI represents the most helpful radiologic
      examination in assessing the outcome of interspinous spacer implantation.

PMID- 19387700
TI  - 2009: The year of innovations in the European Spine Journal.

PMID- 19387701
TI  - Is there a way to diagnose spinal instability in acute burst fractures by
      performing ultrasound?
AB  - The aim of this study is to examine the predictive value of ultrasound
      diagnostics for the assessment of traumatic lesions of the posterior ligament
      complex (PLC) in burst fractures of the thoracolumbar spine. This was a
      prospective validating cohort study. Judgment about instability and treatment of
      burst fractures depends on the condition of the PLC. There have been some studies
      describing underdiagnosis of PLC injuries due to classification problems in
      ligamentary distraction type fractures. The gold standard for assessing these
      lesions is magnetic resonance imaging (MRI). Even then, there are often limits in
      contemporary operational availability and technical limitations of MRI.
      Ultrasound was described being an alternative. In a prospective study, 54 levels
      of 18 patients with acute burst fractures of the thoracic and lumbar spine have
      been examined by ultrasound and additional MRI scans preoperatively. The
      condition (intact vs. ruptured) of supraspinous ligament (SSL) and the
      interspinous ligament has been assessed for the ligaments separately. Hematoma
      below the SSL has also been evaluated as an indirect sign of an injured PLC. In
      all the patients the primary performed operative treatment was a posterior spinal
      instrumentation. Postoperatively the blinded results of the ultrasound procedures
      have been matched against intraoperative and MRI findings. Assessments of all
      target structures have been contributed to the calculation of the sensitivity and
      specificity of ultrasound. A total of 18 patients, 14 males and 4 females, with
      acute burst fractures have been qualified for inclusion in the study. The
      patients' mean age was 43.4 years. Comparing intraoperative findings with
      preoperatively performed investigations, ultrasound archived a sensitivity of
      0.99 and a specificity of 0.75 (P < 0.05) to detect traumatic lesions to the PLC.
      As hypothesized the obtained predictive value using ultrasound correlates closely
      with intraoperative findings. Anyway MRI still seems to be the superior
      diagnostic method for examining the PLC. However, ultrasound can be considered to
      be an adequate alternative method in cases with contraindications for MRI such as
      ferromagnetic side effects, claustrophobia, availability or emergency diagnostics
      in multiple injuries.

PMID- 19387702
TI  - Does walking change the Romberg sign?
AB  - The Romberg sign helps demonstrate loss of postural control as a result of
      severely compromised proprioception. There is still no standard approach to
      applying the Romberg test in clinical neurology and the criteria for and
      interpretation of an abnormal result continue to be debated. The value of this
      sign and its adaptation when walking was evaluated. Detailed clinical examination
      of 50 consecutive patients of cervical myelopathy was performed prospectively.
      For the walking Romberg sign, patients were asked to walk 5 m with their eyes
      open. This was repeated with their eyes closed. Swaying, feeling of instability
      or inability to complete the walk with eyes closed was interpreted as a positive
      walking Romberg sign. This test was compared to common clinical signs to evaluate
      its relevance. Whilst the Hoffman's reflex (79%) was the most prevalent sign
      seen, the walking Romberg sign was actually present in 74.5% of the cases. The
      traditional Romberg test was positive in 17 cases and 16 of these had the walking
      Romberg positive as well. Another 21 patients had a positive walking Romberg
      test. Though not statistically significant, the mean 30 m walking times were
      slower in patients with traditional Romberg test than in those with positive
      walking Romberg test and fastest in those with neither of these tests positive.
      The combination of either Hoffman's reflex and/or walking Romberg was positive in
      96% of patients. The walking Romberg sign is more useful than the traditional
      Romberg test as it shows evidence of a proprioceptive gait deficit in
      significantly more patients with cervical myelopathy than is found on
      conventional neurological examination. The combination of Hoffman's reflex and
      walking Romberg sign has a potential as useful screening tests to detect
      clinically significant cervical myelopathy.

PMID- 19387703
TI  - Sacroplasty in a cadaveric trial: comparison of CT and fluoroscopic guidance with
      and without balloon assistance.
AB  - Sacral insufficiency fractures can cause severe, debilitating pain to patients
      concerned. The incidence of this fracture type correlates with the appearance of
      osteoporosis in the elderly population. A polymethylmethacrylate (PMMA) cement
      injection procedure called sacroplasty has been recently described as an optional
      method for the treatment of this fracture type. However, the correct cement
      placement in the complex anatomical structure of the sacrum is a surgical
      challenge. The aim of the study is to compare the precision, safety, and
      radiation exposure of standard multiplanar fluoroscopy and computed tomography
      (CT) guidance for PMMA application to the sacrum using both balloon-assisted
      sacroplasty and conventional sacroplasty. A controlled experimental investigation
      in a human cadaver trial has been performed. Two imaging and two application
      modalities to monitor percutaneous PMMA injection to the sacrum were examined.
      The application forms were randomized from side to side of the pelvis. We found
      less cement extravasation in the CT-guided groups, but also a significant higher
      radiation exposure (P < 0.05) by using CT guidance. The conventional fluoroscopy
      guided sacroplasty revealed the shortest procedure time (incision to closure
      time) of all treatment groups (P < 0.01). These findings show no difference
      regarding cement extravasation between ballon-assisted and conventional
      sacroplasty. Further, in comparison to fluoroscopy-assisted technique, the CT
      guided cement injection seems to decrease the risk of cement extravasation,
      irrespective of the use of an additional balloon assistance. However, we have to
      consider a greater radiation exposure using CT guidance. Further investigations
      will proof the suitability in the normal course of clinical life.

PMID- 19387704
TI  - Corticosteroids in peri-radicular infiltration for radicular pain: a randomised
      double blind controlled trial. One year results and subgroup analysis.
AB  - The objective of this study is to evaluate the efficacy of corticosteroids in
      patients with radicular pain due to lumbar disc herniation or lumbar spinal
      stenosis through a prospective randomised, double blind controlled trial, and
      whether there was an effect on subsequent interventions such as additional root
      blocks or surgery. Peri-radicular infiltration of corticosteroids has previously
      been shown to offer no additional benefit in patients with sciatica compared to
      local anaesthetic alone. It is not known if the response to peri-radicular
      infiltration is less marked in certain subgroups of patients such as those with
      radicular pain due to lumbar spinal stenosis. Previous studies have suggested
      that peri-radicular infiltration of corticosteroids may obviate the need for
      subsequent interventions and we therefore further investigated this in the
      current study. We randomised 150 patients to receive a single injection with
      either bupivacaine alone or bupivacaine and methylprednisolone. Patients were
      assessed at 6 weeks and 3 months after the injection using standard outcome
      measures including Oswestry Disability Index (ODI), visual analogue score for leg
      pain and patient's subjective assessment of outcome. At 1-year follow-up, we
      looked at the outcome in terms of the need for subsequent interventions such as
      additional root blocks or surgery. At 3-month follow-up, there was no
      statistically significant difference in the standard outcome measures between the
      two injection groups. At a minimum 1-year post injection, there was no difference
      in the need for subsequent interventions in either group. Patients with lumbar
      spinal stenosis had a less marked reduction in the ODI at 3 months with a mean
      change of 3.3 points when compared with 15 points for patients with lumbar disc
      herniation. In conclusion, peri-radicular infiltration of corticosteroids for
      sciatica does not provide any additional benefit when compared to local
      anaesthetic injection alone. Corticosteroids do not obviate the need for
      subsequent interventions such as additional root blocks or surgery.

PMID- 19387705
TI  - Structures and aromaticity of X(2)Y(2)(-) (X = C, Si, Ge and Y = N, P, As)
      anions.
AB  - The equilibrium geometries, total energies, and vibrational frequencies of anions
      X(2)Y(2)(-) (X = C, Si, Ge and Y = N, P, As) are theoretically investigated with
      density functional theory (DFT) method. Our calculation shows that for C(2)N(2)(
      ) species, the D(2h) isomer is the most stable four-membered structure, and for
      other species the C(2v) isomer in which two X atoms are contrapuntal is the most
      stable structure at the B3LYP/6-311 +G(*) level. Wiberg bond index (WBI) and
      negative nucleus-independent chemical shift (NICS) value indicate the existence
      of delocalization in stable X(2)Y(2)(-) structures. A detailed molecular orbital
      (MO) analysis further reveals that stable isomers of these species have strongly
      aromatic character, which strengthens the structural stability and makes them
      closely connected with the concept of aromaticity.

PMID- 19387706
TI  - Horses (Equus caballus) select the greater of two quantities in small numerical
      contrasts.
AB  - The ability to select the greater numerosity over another in small sets seems to
      stem from the calculation of which set contains more, and has been taken as
      evidence of a primordial representation at the roots of the primate numerical
      system. We tested 56 horses (Equus caballus) in a paradigm previously used with
      human infants and nonhuman primates. Horses saw two quantities paired in
      contrasts-2 versus 1, 3 versus 2, 6 versus 4 and a control for volume, 2 versus 1
      big-and had to make a choice by snout touching the container holding the
      numerosity selected. The horses spontaneously selected the greater of the two
      quantities when the numerosities were small. These results add to evidence
      showing spontaneous quantity assessment in a variety of species.

PMID- 19387707
TI  - Clinical features and treatment outcomes of vancomycin-intermediate
      Staphylococcus aureus (VISA) and heteroresistant vancomycin-intermediate
      Staphylococcus aureus (hVISA) in a tertiary care institution in Singapore.
AB  - This retrospective case-control study was undertaken to review the clinical
      features associated with heteroresistant vancomycin-intermediate Staphylococcus
      aureus (hVISA) and vancomycin-intermediate S. aureus (VISA) infections and the
      local impact they have on clinical outcome. Compared with vancomycin-susceptible
      S. aureus (n = 30), hVISA and VISA infections (n = 10) are found to be associated
      with a longer period of prior glycopeptide use (P = 0.01), bone/joint (P < 0.01)
      and prosthetic infections (P = 0.04), as well as treatment failure, as evidenced
      by longer bacteremic (P < 0.01) and culture positivity (P < 0.01) periods. This
      was observed to have resulted in longer hospital length of stay (P < 0.01) and
      total antibiotic therapy duration (P = 0.01). There was, however, no significant
      difference in the overall patient mortality or the hospitalization cost (P =
      0.12) in both groups. Clinicians should be cognizant of the association between
      hVISA/VISA with high bacterial load deep-seated infections. We recommend targeted
      and even universal screening for hVISA/VISA in methicillin-resistant S. aureus
      (MRSA) infections.

PMID- 19387708
TI  - CT features of pulmonary artery sarcoma: critical aid to a challenging diagnosis.
AB  - Pulmonary artery sarcoma is an uncommon and highly malignant neoplasm that
      presents a diagnostic challenge to radiologists due to its tendency to mimic the
      more common condition of pulmonary thromboembolism. Presented in this case report
      is a patient with pulmonary artery sarcoma who was initially diagnosed with
      saddle pulmonary embolism based upon computed tomography (CT) findings. The case
      emphasizes the importance of including pulmonary artery sarcoma in the
      differential diagnosis of a large filling defect in the pulmonary arteries when
      specific CT findings are identified in the appropriate clinical setting.

PMID- 19387709
TI  - Clinical evaluation of a lumbar interspinous dynamic stabilization device (the
      Wallis system) with a 13-year mean follow-up.
AB  - The authors determined current health status of patients who had been included in
      a long-term survivorship analysis of a lumbar dynamic stabilizer. Among 133
      living patients, 107 (average age at surgery, 44.2 +/- 9.9 years) completed
      health questionnaires. All patients had initially been scheduled for
      decompression and fusion for canal stenosis, herniated disc, or both. In 20
      patients, the implant was removed, and fusion was performed. The other 87 still
      had the dynamic stabilizer. Satisfaction, Oswestry disability index, visual
      analog scales for back and leg pain, short-form (SF-36) quality-of-life physical
      composite score, physical function, and social function were significantly better
      (p < or = 0.05) in the patients who still had the dynamic stabilization device.
      SF-36 scores of the fused subgroup were no worse than those reported elsewhere in
      patients who had primary pedicle-screw enhanced lumbar fusion. This anatomy
      sparing device provided a good 13-year clinical outcome and obviated arthrodesis
      in 80% of patients.

PMID- 19387710
TI  - Young's modulus of elasticity of Schlemm's canal endothelial cells.
AB  - Schlemm's canal (SC) endothelial cells are likely important in the physiology and
      pathophysiology of the aqueous drainage system of the eye, particularly in
      glaucoma. The mechanical stiffness of these cells determines, in part, the extent
      to which they can support a pressure gradient and thus can be used to place
      limits on the flow resistance that this layer can generate in the eye. However,
      little is known about the biomechanical properties of SC endothelial cells. Our
      goal in this study was to estimate the effective Young's modulus of elasticity of
      normal SC cells. To do so, we combined magnetic pulling cytometry of isolated
      cultured human SC cells with finite element modeling of the mechanical response
      of the cell to traction forces applied by adherent beads. Preliminary work showed
      that the immersion angles of beads attached to the SC cells had a major influence
      on bead response; therefore, we also measured bead immersion angle by confocal
      microscopy, using an empirical technique to correct for axial distortion of the
      confocal images. Our results showed that the upper bound for the effective
      Young's modulus of elasticity of the cultured SC cells examined in this study, in
      central, non-nuclear regions, ranged between 1,007 and 3,053 Pa, which is similar
      to, although somewhat larger than values that have been measured for other
      endothelial cell types. We compared these values to estimates of the modulus of
      primate SC cells in vivo, based on images of these cells under pressure loading,
      and found good agreement at low intraocular pressure (8-15 mm Hg). However,
      increasing intraocular pressure (22-30 mm Hg) appeared to cause a significant
      increase in the modulus of these cells. These moduli can be used to estimate the
      extent to which SC cells deform in response to the pressure drop across the inner
      wall endothelium and thereby estimate the extent to which they can generate
      outflow resistance.

PMID- 19387711
TI  - An assessment of ductus venosus tapering and wave transmission from the fetal
      heart.
AB  - Pressure and flow pulsations in the fetal heart propagate through the precordial
      vein and the ductus venosus (DV) but are normally not transmitted into the
      umbilical vein (UV). Pulsations in the umbilical vein do occur, however, in early
      pregnancy and in pathological conditions. Such transmission into the umbilical
      vein is not well understood. In particular, the effect of the impedance changes
      in the DV due to its tapered geometry is not known. This paper presents a
      mathematical model that we developed to study the transmission of pulsations,
      originating in the fetal heart, through the DV to the umbilical vein. In our
      model, the tapered geometry of the DV was found to be of minor importance and the
      only effective reflection site in the DV appears to be at the DV inlet.
      Differences between the DV inlet and outlet flow were also found to be minor for
      medium to large umbilical vein-DV diameter ratios. Finally, the results of a
      previously proposed lumped model were found to agree well with the present model
      of the DV-umbilical vein bifurcation.

PMID- 19387713
TI  - Laboratory-scale biofiltration of acrylonitrile by Rhodococcus rhodochrous DAP
      96622 in a trickling bed bioreactor.
AB  - Acrylonitrile (ACN), a volatile component of the waste generated during the
      production of acrylamide, also is often associated with aromatic contaminants
      such as toluene and styrene. Biofiltration, considered an effective technique for
      the treatment of volatile hydrocarbons, has not been used to treat volatile
      nitriles. An experimental laboratory-scale trickling bed bioreactor using cells
      of Rhodococcus rhodochrous DAP 96622 supported on granular activated carbon (GAC)
      was developed and evaluated to assess the ability of biofiltration to treat ACN.
      In addition to following the course of treatability of ACN, kinetics of ACN
      biodegradation during both recycle batch and open modes of operation by
      immobilized and free cells were evaluated. For fed-batch mode bioreactor with
      immobilized cells, almost complete ACN removal (>95%) was achieved at a flow rate
      of 0.1 microl/min ACN and 0.8 microl/min toluene (TOL) (for comparative purposes
      this is equivalent to 6.9 mg l(-1) h(-1) ACN and 83.52 mg l(-1) h(-1) TOL). In a
      single-pass mode bioreactor with immobilized cells, at ACN inlet loads of 100-200
      mg l(-1) h(-1) and TOL inlet load of approximately 400 mg l(-1) h(-1), with empty
      bed retention time (EBRT) of 8 min, ACN removal efficiency was approximately 90%.
      The three-dimensional structure and characteristics of the biofilm were
      investigated using confocal scanning laser microscopy (CSLM). CLSM images
      revealed a robust and heterogeneous biofilm, with microcolonies interspersed with
      voids and channels. Analysis of the precise measurement of biofilm
      characteristics using COMSTAT agreed with the assumption that both biomass and
      biofilm thickness increased along the carbon column depth.

PMID- 19387714
TI  - The variability of processes involved in transgene dispersal-case studies from
      Brassica and related genera.
AB  - BACKGROUND, AIM, AND SCOPE: We strive to predict consequences of genetically
      modified plants (GMPs) being cultivated openly in the environment, as human and
      animal health, biodiversity, agricultural practise and farmers' economy could be
      affected. Therefore, it is unfortunate that the risk assessment of GMPs is
      burdened by uncertainty. One of the reasons for the uncertainty is that the GMPs
      are interacting with the ecosystems at the release site thereby creating
      variability. This variability, e.g. in gene flow, makes consequence analysis
      difficult. The review illustrates the great uncertainty of results from gene-flow
      analysis. MAIN FEATURES: Many independent experiments were performed on the
      individual processes in gene flow. The results comprise information both from
      laboratory, growth chambers and field trials, and they were generated using
      molecular or phenotypic markers and analysis of fitness parameters. Monitoring of
      the extent of spontaneous introgression in natural populations was also
      performed. Modelling was used as an additional tool to identify key parameters in
      gene flow. RESULTS: The GM plant may affect the environment directly or
      indirectly by dispersal of the transgene. Magnitude of the transgene dispersal
      will depend on the GM crop, the agricultural practise and the environment of the
      release site. From case-to-case these three factors provide a variability that is
      reflected in widely different likelihoods of transgene dispersal and fitness of
      introgressed plants. In the present review, this is illustrated through a bunch
      of examples mostly from our own research on oilseed rape, Brassica napus. In the
      Brassica cases, the variability affected all five main steps in the process of
      gene dispersal. The modelling performed suggests that in Brassica, differences in
      fitness among plant genome classes could be a dominant factor in the
      establishment and survival of introgressed populations. DISCUSSION: Up to now,
      experimental analyses have mainly focused on studying the many individual
      processes of gene flow. This can be criticised, as these experiments are normally
      carried out in widely different environments and with different genotypes, and
      thus providing bits and pieces difficult to assemble. Only few gene-flow studies
      have been performed in natural populations and over several plant generations,
      though this could give a more coherent and holistic view. CONCLUSION: The
      variability inherent in the processes of gene flow in Brassica is apparent and
      remedies are wished for. One possibility is to expose the study species to
      additional experiments and monitoring, but this is costly and will likely not
      cover all possible scenarios. Another remedy is modelling gene flow. Modelling is
      a valuable tool in identifying key factors in the gene-flow process for which
      more knowledge is needed, and identifying parameters and processes which are
      relatively insensitive to change and therefore require less attention in future
      collections of data. But the interdependence between models and experimental data
      is extensive, as models depend on experimental data for their development or
      testing. RECOMMENDATIONS: More and more transgenic varieties are being grown
      worldwide harbouring genes that might potentially affect the environment (e.g.
      drought tolerance, salt tolerance, disease tolerance, pharmaceutical genes). This
      calls for a thorough risk assessment. However, in Brassica, the limited and
      uncertain knowledge on gene flow is an obstacle to this. Modelling of gene flow
      should be optimised, and modelling outputs verified in targeted field studies and
      at the landscape level. Last but not least, it is important to remember that
      transgene flow in itself is not necessarily a thread, but it is the consequences
      of gene flow that may jeopardise the ecosystems and the agricultural production.
      This emphasises the importance of consequence analysis of genetically modified
      plants.

PMID- 19387715
TI  - Scapular muscle activation and co-activation following a fatigue task.
AB  - Scapular muscles precisely move the scapulothoracic articulation and if fatigued
      may contribute to pathology. Fatigue of serratus anterior may be a mechanism for
      shoulder pathology by altering scapula motions and requiring compensation by
      other shoulder muscles. A total of 28 asymptomatic subjects performed a task to
      fatigue the serratus anterior, while muscle activity was recorded from three
      muscles. Mean normalized activation levels and activation ratios were examined
      before and after the fatigue task during arm elevation and lowering. All muscles
      demonstrated meaningful declines in the median frequency of the electromyographic
      signal during the task. Following the task, only the upper trapezius had higher
      mean activation levels (mean difference 10.79% MVIC), while the serratus
      anterior/lower trapezius activation ratio was altered (mean difference -0.3).
      Higher mean upper trapezius activation may be compensatory for fatigue of other
      shoulder muscles and may reflect fiber type or central control mechanisms.
      Serratus anterior eccentric endurance training may be beneficial for the
      prevention of shoulder pathology.

PMID- 19387716
TI  - Radiographic results of combined Salter innominate and femoral osteotomy in Legg
      Calve-Perthes disease in older children.
AB  - PURPOSE: Treatment of Legg-Calve-Perthes disease in older children with greater
      involvement of the femoral head remains uncertain. Innominate, femoral or
      combined innominate and femoral osteotomies are generally performed to better
      contain and provide more coverage of the femoral head by the acetabulum with the
      objective of achieving a more spherical head and a congruent joint. The purpose
      of the study was to evaluate the radiographic outcomes of simultaneous femoral
      and pelvic osteotomies. METHODS: We reviewed the radiographic changes of 20
      patients with Legg-Calve-Perthes disease with a disease onset of over eight years
      of age who had undergone combined femoral and Salter innominate osteotomies. The
      hips in these 17 males and 3 females comprised 11 lateral pillar (LP) group B, 7
      B/C, and 2 C. The patients were evaluated with a mean follow-up of five years and
      five months using the Stulberg radiographic assessment. RESULTS: Among those 20
      hips, six became Stulberg II (SII), nine SIII, and five SIV. From the 11 LPB
      hips, five became SII, four SIII, and two SIV. The seven LPB/C turned out to be
      SII in one case, SIII in four, and SIV in two hips. One of the two LPC hips
      became SIII and the other one SIV. The three female patients had one LPB, one
      LPB/C, and one LPC hip, and surgery resulted in SIII hips in all three cases.
      Eight of these 20 cases were older than 11 years of age at the time of surgery,
      and all had fair or poor hips. CONCLUSIONS: Simultaneous femoral and Salter
      innominate osteotomies in older children with a higher LP grouping can marginally
      improve the radiographic outcome in comparison with the natural history in LPB/C
      and LPC cases by converting a number of poor results to fair results.

PMID- 19387717
TI  - [6S]-5-Methyltetrahydrofolate enhances folate status in rats fed growing-up milk.
AB  - BACKGROUND AND AIMS: To investigate the efficiency of [6S]-5
      methyltetrahydrofolate or Metafolin ([6S]-5-CH(3)-H(4)folate) on the recovery of
      folate status, we conducted a depletion-repletion rat model study using a growing
      up milk as the folate carrier. METHODS: The effect of [6S]-5-CH(3)-H(4)folate was
      compared to that of folic acid (PGA or Pte-Glu), by feeding two groups of folate
      depleted rats a diet of fortified growing-up milk containing either 1,000
      microg/l (2.2655 micromol/l) of Pte-Glu or 1,041.91 microg/l (2.2655 micromol/l)
      of [6S]-5-CH(3)-H(4)folate over a 4-week period. At the end of the study, the
      folate concentration in plasma, erythrocytes and liver was measured to establish
      the folate status of the animals. The folate content was determined in the plasma
      and erythrocytes by a time-resolved fluoroimmunoassay method and in the liver by
      a HPLC method. RESULTS: Plasma, erythrocyte and liver folate concentrations were
      significantly (P < 0.001) lower after a depletion period in rats fed the folate
      deficient diet compared to rats fed a control diet. The folate form used
      significantly influenced the folate concentration in erythrocytes and liver, but
      not in plasma, after the rats' body folate reserves were replenished by consuming
      the fortified growing-up milk. Thus, rats fed [6S]-5-CH(3)-H(4)folate-fortified
      growing-up milk showed significantly higher folate content in erythrocytes and
      liver (1,100.37 ng/ml and 4.22 microg/g, respectively), than did those fed Pte
      Glu-fortified growing-up milk (827.71 ng/ml and 3.04 microg/g, respectively, in
      erythrocytes and liver). CONCLUSION: We conclude that the natural diastereomer
      [6S]-5-CH(3)-H(4)folate may adequately serve as an alternative to folic acid for
      the folate fortification of infant foods.

PMID- 19387718
TI  - Temperamental predictors of externalizing problems among boys and girls: a
      longitudinal study in a high-risk sample from ages 3 months to 15 years.
AB  - In a high-risk community sample, we examined the role of regulative temperament
      and emotionality as well as the extent of gender specificity in the development
      of externalizing problems. 151 boys and 157 girls born at differing degrees of
      obstetric and psychosocial risk were followed from birth into adolescence. In
      infancy and childhood, NYLS-derived temperamental characteristics were assessed
      by a highly structured parent interview and standardized behavioral observations.
      At age 15 years, externalizing problems were measured by the Child Behavior
      Checklist. As revealed by multiple linear regression and logistic regression, low
      regulative abilities predicted adolescent behavioral and attentional problems
      over and above obstetric and psychosocial risks. Gender specificity was found in
      the strength of the association rather than in the kind with a stronger long-term
      prediction from infant and toddler temperament in girls. Compared to regulative
      abilities, temperament factors describing aspects of mood and fear/withdrawal
      versus approach tendencies played a minor role in the development of
      externalizing problems. Findings are discussed in terms of gender-specific risk
      factors and possible differential developmental trajectories to subtypes of
      disruptive behavior.

PMID- 19387719
TI  - Acute myocardial infarction as the presenting symptom of systemic lupus
      erythematosus.
AB  - We report a case of acute myocardial infarction due to non-antiphospholipid
      related coronary artery thrombosis as the presenting manifestation of systemic
      lupus erythematosus in a young patient. We present the acute workup and the
      results of successful transcatheter coronary intervention. The causes of acute
      myocardial infarction and coronary artery thrombosis in pediatric patients are
      reviewed.

PMID- 19387721
TI  - Microbial enrichment of a novel growing substrate and its effect on plant growth.
AB  - The quality of torrefied grass fibers (TGF) as a new potting soil ingredient was
      tested in a greenhouse experiment. TGF was colonized with previously selected
      microorganisms. Four colonization treatments were compared: (1) no inoculants,
      (2) the fungus Coniochaeta ligniaria F/TGF15 alone, (3) the fungus followed by
      inoculation with two selected bacteria, and (4) the fungus with seven selected
      bacteria. Cultivation-based and DNA-based methods, i.e., PCR-DGGE and BOX-PCR,
      were applied to assess the bacterial and fungal communities established in the
      TGF. Although colonization was not performed under sterile conditions, all
      inoculated strains were recovered from TGF up to 26 days incubation. Stable
      fungal and bacterial populations of 10(8) and 10(9) CFU/g TGF, respectively, were
      reached. As a side effect of the torrefaction process that aimed at the chemical
      stabilization of grass fibers, potentially phytotoxic compounds were generated.
      These phytotoxic compounds were cold-extracted from the fibers and analyzed by
      gas chromatography mass spectrometry. Four of 15 target compounds that had
      previously been found in the extract of TGF were encountered, namely phenol, 2
      methoxyphenol, benzopyran-2-one, and tetrahydro-5,6,7,7a-benzofuranone. The
      concentration of these compounds decreased significantly during incubation. The
      colonized TGF was mixed with peat (P) in a range of 100%:0%, 50%:50%, 20%:80%,
      and 0%:100% TGF/P (w/w), respectively, to assess suitability for plant growth.
      Germination of tomato seeds was assessed three times, i.e., with inoculated TGF
      that had been incubated for 12, 21, and 26 days. In these tests, 90-100% of the
      seeds germinated in 50%:50% and 20%:80% TGF/P, whereas on average only 50% of the
      seeds germinated in pure TGF. Germination was not improved by the microbial
      inoculants. However, plant fresh weight as well as leaf area of 28-day-old tomato
      plants were significantly increased in all treatments where C. ligniaria F/TGF15
      was inoculated compared to the control treatment without microbial inoculants.
      Colonization with C. ligniaria also protected the substrate from uncontrolled
      colonization by other fungi. The excellent colonization of TGF by the selected
      plant-health promoting bacteria in combination with the fungus C. ligniaria
      offers the possibility to create disease suppressive substrate, meanwhile
      replacing 20% to 50% of peat in potting soil by TGF.

PMID- 19387720
TI  - Hypocalcemic rickets and dilated cardiomyopathy: case reports and review of
      literature.
AB  - Internationally, there have been isolated case reports published of children
      presenting with dilated cardiomyopathy (DCM) in the setting of undiagnosed
      rickets. Although there has been an increased prevalence of rickets in the United
      States, there has been only one documented case of associated DCM. At our
      institution, a hospital database search was conducted from year 1997 to year 2007
      to identify patients with confirmed vitamin D deficiency in addition to DCM.
      Through this search, four exclusively breast-fed African American infants were
      identified. These infants presented with congestive heart failure secondary to
      DCM and, at their admission, were found to have laboratory evidence consistent
      with hypocalcemic rickets. These patients responded dramatically to treatment
      with vitamin D and calcium, and cardiac function returned to normal within
      months. Early recognition of vitamin D deficiency was an important factor in
      these patients' clinical course. These case reviews present a rare, serious
      complication of vitamin D-deficient rickets and support evidence for prevention
      of this nutritional deficiency with vitamin D supplementation in exclusively
      breast-fed infants.

PMID- 19387722
TI  - Idiopathic proximal hemimegacolon: radiologic findings and analyses of clinical
      and physiological characteristics.
AB  - BACKGROUND: Idiopathic megacolon with bowel dilatation only proximal to the
      splenic flexure is an uncommon and poorly characterized disease. This study aimed
      to identify the characteristics of idiopathic proximal hemimegacolon. METHODS:
      Five patients (2 males and 3 females) were diagnosed to have idiopathic proximal
      hemimegacolon and their radiologic, clinical, and physiological characteristics
      were reviewed. Hirschsprung's disease and other known causes of bowel dilatation
      were excluded by the presence of rectoanal inhibitory reflex and reviewing
      medical records. RESULTS: Mean age at diagnosis and symptom onset were 50.4 years
      and 47.2 years, respectively. Four patients presented with constipation, and all
      five patients showed abdominal distention and abdominal pain. Four patients were
      successfully treated and maintained only with laxatives and prokinetics without
      enema. Only one patient underwent surgery for intractable constipation. Mean
      maximal diameters of each segment of colons measured by computed tomography were
      57.5 mm, 69.3 mm, 73.0 mm, 33.3 mm, 24.0 mm, and 27.3 mm for cecum, ascending
      colon, transverse colon, descending colon, sigmoid colon, and rectum,
      respectively. Colon transit time was delayed in four patients with mean value of
      90.0 h. CONCLUSIONS: These results indicated that patients with idiopathic
      proximal hemimegacolon may be treated successfully only with medical therapy in
      most cases.

PMID- 19387723
TI  - Wedge-shaped excision and modified vertical mattress suture fully buried in a
      multilayered and tensioned wound closure.
AB  - BACKGROUND: A successful deep multilayered wound suture should provide a firm
      tension-relieving closure, good wound-edge eversion, hemostasis, and minimal
      intradermal extraneous materials. However, this is not always achieved with a
      single standard technique. The authors describe their modification of a wound
      closure method that can rapidly and reliably achieve these results. METHODS: A
      wedge-shaped excision was adopted to obtain a trapezoid pattern transect, after
      which a modified fully buried vertical mattress suture technique was used to
      close the wound. These techniques were compared with the standard excision and
      suture techniques used for the same patient at different times after surgery.
      RESULTS: The wedge-shaped excision can facilitate good wound-edge eversion, and
      the modified fully buried vertical mattress suture can provide firm tension
      relief and optimal apposition. Compared with conventional excision and suture
      techniques, the described techniques brought about a better outcome in terms of
      hypertrophic scar prevention. CONCLUSION: The described modified technique seems
      to be more efficient than conventional procedures used to prevent hypertrophic
      scar formation.

PMID- 19387724
TI  - Evaluation of the impact of the natural forest protection program on rural
      household livelihoods.
AB  - In this study, we estimated the impact on local household livelihoods of the
      Natural Forest Protection Program (NFPP), which is the largest logging-ban
      program in the world, which aims to protect watersheds and conserve natural
      forests. In doing so, we used a series of microeconometric policy-evaluation
      techniques to assess the impacts of the NFPP on two interrelated facets of
      household livelihoods: income and off-farm labor supply. We found that the NFPP
      has had a negative impact on incomes from timber harvesting but has actually had
      a positive impact on total household incomes from all sources. Furthermore, we
      found that off-farm labor supply outside the village has increased more rapidly
      in NFPP than in non-NFPP areas. Based on these results, policy implications for
      household livelihoods were drawn and are presented herein.

PMID- 19387725
TI  - Nutritional risk factors in planned oncologic surgery: what clinical and
      biological parameters should be routinely used?
AB  - BACKGROUND: Screening for malnutrition is recommended in hospitalized and planned
      surgical patients. The aim of this study was to analyze the feasibility and
      routine prognostic value of using the principal recommended nutritional screening
      and evaluation tools for cancer patients undergoing major surgery. METHODS: This
      study is a prospective, 3-month, multicenter observational trial recording weight
      loss, body mass index, albumin, transthyretin, and PG-SGA. The morbidity rate was
      assessed on the basis of major complications (MC), whether of an infectious (MIC)
      or noninfectious (MNIC) nature. RESULTS: Two hundred seventy-five patients were
      recruited at nine centers. The following percentages were recorded with respect
      to morbidity: 28.4% MC, 12.7% MIC, and 22.2% MNIC. Univariate analysis revealed a
      statistical association only between weight loss greater than 10% and MIC and
      hospital stay. A weight loss of 15% is required to demonstrate an association
      with either MC, MIC, or MNIC. Body mass index (BMI) was associated only with
      MNIC, PG-SGA with MC, and albumin <30 g/l was strongly associated with all types
      of morbidity (MC, MIC, MNIC). Multivariate analysis indicated that only albumin
      <30 g/l and an operating time of more than 4 h are significantly associated with
      morbidity. CONCLUSIONS: In this study, the best nutritional factor for detecting
      the risk of MC is albumin levels below 30 g/l. A weight loss greater than 15% is
      required to obtain a statistically significant correlation with the existence of
      MC.

PMID- 19387726
TI  - Benefits versus risks: a prospective audit. Feeding jejunostomy during
      esophagectomy.
AB  - BACKGROUND: The purpose of this prospectively collected database is to evaluate
      the safety, efficacy, and utility of postoperative jejunostomy feeding in terms
      of achieving nutritional goals and evaluating gastrointestinal and mechanical
      complications in patients undergoing esophagectomy. METHODS: The study included
      204 consecutive patients who underwent esophagectomy for various benign and
      malignant conditions. All patients underwent Witzel feeding jejunostomy at the
      time of laparotomy. Patients were followed prospectively to record nutritional
      intake, type of feed administered, rate progression, tolerance, and complications
      either mechanical or gastrointestinal. RESULTS: Feeding jejunostomy could be
      performed in 99.5% patients; 6.0% of the patients had a blocked catheter during
      the course of feeding. The target calorie requirement could be achieved in 78% of
      patients by third day. In all, 95% of patients could be successfully fed
      exclusively by jejunostomy catheter during the postoperative period. Minor
      gastrointestinal complications developed in 15% of the patients and were managed
      by slowing the rate of infusion or administering medication. Patients spent a
      mean of 16.67 +/- 22.00 days (range 0-46 days) on jejunostomy feeding after
      surgery; however, 13% required prolonged jejunostomy feeding beyond 30 days.
      Altogether, 64% of the patients with an anastomotic leak and 50% of the patients
      with postoperative complications required catheter jejunostomy feeding beyond 30
      days. The mean duration for which jejunostomy tube feeding was used was
      significantly higher for patients who developed anastomotic disruptions (33.05 +/
      16.24 vs. 14.69 +/- 19.04 days; p = 0.000) and postoperative complications
      (26.67 +/- 25.56 vs. 14.52 +/- 18.64 days; p = 0.000) when compared to those
      without disruption or complications. There were no serious complications related
      to the feeding catheter that required reintervention. There was no difference in
      the mean body weight or weight deficit at the end of 10 days and at 1 month in
      patients who developed complications or anastomotic disruption when compared to
      their counterparts. No patient died as a result of a complication related to the
      feeding jejunostomy. CONCLUSIONS: Tube jejunostomy feeding is an effective method
      for providing nutritional support in patients undergoing esophagectomy, and it
      allows home support for the subset who fail to thrive. Prolonged tube feeding was
      continued in patients developing anastomotic disruptions and postoperative
      complications. Feeding jejunostomy has a definitive role to play in the
      management of the patients undergoing esophagectomy.

PMID- 19387727
TI  - Chronic portal vein thrombosis after liver transplantation in a child treated by
      a combined minimally invasive approach.
AB  - Portal vein thrombosis (PVT) after orthotopic liver transplantation is an
      infrequent complication, and when it is present surgical treatment is considered
      for traditional management. Percutaneous transhepatic portal vein angioplasty has
      been described as an option to treat PVT with a lower morbidity than conventional
      surgical treatments. This article describes a case of chronic PVT in a child
      after a living donor liver transplantation managed by percutaneous transhepatic
      and surgical approaches.

PMID- 19387728
TI  - Primary patency of Wallstents in malignant bile duct obstruction: single vs. two
      or more noncoaxial stents.
AB  - The purpose of this study was to determine the primary patency of two or more
      noncoaxial self-expanding metallic Wallstents (Boston Scientific, Natick, MA) and
      to compare this with the primary patency of a single stent in malignant bile duct
      obstruction. From August 2002 to August 2004, 127 patients had stents placed for
      malignant bile duct obstruction. Forty-five patients were treated with more than
      one noncoaxial self-expanding metallic stents and 82 patients had a single stent
      placed. Two patients in the multiple-stent group were lost to follow-up. The
      primary patency period was calculated from the date of stenting until the first
      poststenting intervention for stent occlusion, death, or the time of last
      documented follow-up. The patency of a single stent was significantly different
      from that of multiple stents (P = 0.0004). In the subset of patients with high
      bile duct obstruction, the patency of a single stent remained significantly
      different from that of multiple stents (P = 0.02). In the single-stent group,
      there was no difference in patency between patients with high vs. those with low
      bile duct obstruction (P = 0.43). The overall median patency for the multistent
      group and the single-stent group was 201 and 261 days, respectively. In
      conclusion, the patency of a single stent placed for malignant low or high bile
      duct obstruction is similar, and significantly longer than, that of multiple
      stents placed for malignant high bile duct obstruction. Given the median patency
      of 201 days, when indicated, percutaneous stenting of multiple bile ducts is an
      effective palliative measure for patients with malignant high bile duct
      obstruction.

PMID- 19387729
TI  - Transcatheter embolization of bronchial artery arising from left circumflex
      coronary artery in a patient with massive hemoptysis.
AB  - It has been reported that anastomoses between the bronchial and the coronary
      arteries can become dilated and functional in certain diseases, provoking angina
      pectoris through coronary steal syndrome. The condition can be treated with
      endovascular or surgical management. It is possible that this abnormality may be
      associated with hemoptysis in patients with parenchymal or vascular disease of
      the lung but this condition is very rare. We present the coronary CT angiographic
      findings of bronchial arteries arising from the left coronary artery and their
      treatment with transcatheter embolization for the control of massive hemoptysis.

PMID- 19387730
TI  - Retroperitoneal extraskeletal osteosarcoma: imaging findings and transarterial
      chemoembolization.
AB  - Extraskeletal osteosarcoma (EOS) is an uncommon and usually highly aggressive
      mesenchymal tumor. Retroperitoneal extraskeletal osteosarma (REOS) is exceedingly
      rare. Due to the rare nature of the disease, both the diagnosis and the
      management of REOS can be challenging. We present the clinical history, CT
      findings, angiographic manifestations, and use of transarterial chemoembolization
      for treatment in a case of REOS. To our knowledge, the angiographic features of
      and attempt at transarterial treatment of REOS have not been reported in the
      literature.

PMID- 19387731
TI  - Application of the AMPLATZER vascular plug in endovascular occlusion of dialysis
      accesses.
AB  - The purpose of this study was to share our initial experience with the AMPLATZER
      Vascular Plug (AVP) in occluding dialysis accesses. Between January 2007 and
      October 2008, five patients with autogenous and one patient with prosthetic
      accesses were referred for endovascular occlusion owing to central venous
      obstruction (n = 4) and dialysis-associated steal syndrome (n = 2) leading to
      disabling complications. We used a single AVP in two patients, double AVPs in two
      patients, and double AVPs and n-butyl 2-cyanoacrylate in one patient with an
      autogenous access. Two coils were deployed between two AVPs to occlude the
      prosthetic graft. Immediate success was achieved in all patients, with no
      complications. Mean follow-up time was 13 months (range, 1-21 months) and none of
      the patients had experienced symptom recurrence as of the time of writing. The
      AVP allows simple, precise, and reliable dialysis access occlusion without
      significant complications when surgical ligation is not preferred. It can be used
      with other embolizing agents to provide occlusion in the case of failure.

PMID- 19387732
TI  - Analysis of nontarget embolization mechanisms during embolization and
      chemoembolization procedures.
AB  - Complications of embolization and chemoembolization remain a problem even with
      the development of low-profile catheter material and the introduction of new
      embolization agents. In recent years many new embolization materials have become
      available for clinical use, so the possibilities and limitations of these new
      materials must be understood to allow safe and effective embolization. Although
      up to now some scientific work has been published reporting the basic risk of
      embolization procedures, the underlying pathomechanism remains the object of
      speculation. Besides complications like drug toxicity, allergic reactions, and
      bleeding of the puncture site, the characteristics of embolization materials must
      be known to understand the potential complications of nontarget embolization and
      reflux of embolization material. This article gives an overview of established
      and new embolization materials, their potential risks, and the underlying
      pathophysiology.

PMID- 19387733
TI  - A novel "cheese wire" technique for stent positioning following difficult iliac
      artery subintimal dissection and aortic re-entry.
AB  - Subintimal wire dissection is a well-established method for traversing difficult
      vascular occlusions. This technique relies on re-entry of the true lumen distal
      to the occlusion, which may be difficult in diseased vessels with significant
      calcification. This case report describes a novel "cheese wire" technique to
      allow stent positioning without the use of proprietary re-entry devices.

PMID- 19387734
TI  - An N-ethyl-N-nitrosourea mutagenesis recessive screen identifies two candidate
      regions for murine cardiomyopathy that map to chromosomes 1 and 15.
AB  - N-ethyl-N-nitrosourea (ENU) mutagenesis screens have been successful for
      identifying genes that affect important biological processes and diseases.
      However, for heart-related phenotypes, these screens have been employed
      exclusively for developmental phenotypes, and to date no adult cardiomyopathy
      causing genes have been discovered through a mutagenesis screen. To identify
      novel disease-causing and disease-modifying genes for cardiomyopathy, we
      performed an ENU recessive mutagenesis screen in adult mice. Using noninvasive
      echocardiography to screen for abnormalities in cardiac function, we identified a
      heritable cardiomyopathic phenotype in two families. To identify the chromosomal
      regions where the mutations are localized, we used a single nucleotide
      polymorphism (SNP) panel for genetic mapping of mouse mutations. This panel
      provided whole-genome linkage information and identified the mutagenized
      candidate regions at the proximal end of chromosome 1 (family EN1), and at the
      distal end of chromosome 15 (family EN25). We have identified 94 affected mice in
      family EN1 and have narrowed the candidate interval to 1 Mb. We have identified
      20 affected mice in family EN25 and have narrowed the candidate interval to 12
      Mb. The identification of the genes responsible for the observed phenotype in
      these families will be strong candidates for disease-causing or disease-modifying
      genes in patients with heart failure.

PMID- 19387735
TI  - Loss of heterozygosity at the FLCN locus in early renal cystic lesions in dogs
      with renal cystadenocarcinoma and nodular dermatofibrosis.
AB  - Small, macroscopically visible cysts on the surface of the kidneys were observed
      in eight 6-8-week-old puppies diagnosed with renal cystadenocarcinoma and nodular
      dermatofibrosis (RCND). Histologic examination of the renal cortices in these
      puppies reveals numerous small cystic tubular changes. Hyperplastic change of the
      epithelial lining of cysts is frequently observed. By laser-capture
      microdissection we have sampled epithelial cells from such early renal cystic
      lesions in eight paternal half-sibs diagnosed with RCND. DNA was obtained from
      the laser-captured material, and all coding exons of the germline-mutated FLCN
      gene were sequenced to detect putative second hits. Samples from 31 independent
      hyperplastic epithelial cell sections of tubular microcysts of the RCND siblings
      were examined as well as normal control samples of the tissue sections. Loss of
      heterozygosity was detected in 35% of the transformed samples. The frequently
      observed loss of heterozygosity at the FLCN locus in atypical epithelial cells
      lining the cysts suggests that loss of heterozygosity/function of the FLCN gene
      may contribute to neoplastic transformation of renal epithelial cells at a very
      early age of RCND-affected dogs. The transformed renal epithelial cells seem to
      grow slowly in young puppies, which indicates that other mutational events are
      required for the development of tumors in adult dogs.

PMID- 19387736
TI  - Intravenous immunoglobulin therapy for refractory interstitial lung disease
      associated with polymyositis/dermatomyositis.
AB  - Interstitial lung disease (ILD) associated with polymyositis/dermatomyositis (ILD
      PM/DM), including amyopathic dermatomyositis (ADM), is recognized as an important
      condition because it frequently causes death, despite intensive therapy with high
      dose corticosteroid and immunosuppressive agents, such as cyclosporine A and
      cyclophosphamide. Intravenous immunoglobulin therapy (IVIG) has shown efficacy
      for myopathy associated with PM/DM, but its usefulness for ILD-PM/DM is unclear.
      This study was designed to investigate the efficacy of IVIG for refractory ILD
      PM/DM. A review was made of medical charts of five patients (2 men and 3 women)
      who were treated with IVIG for refractory ILD-PM/DM resistant to high-dose
      corticosteroid and cyclosporine A and/or cyclophosphamide. One patient had acute
      ILD-PM and four patients had acute ILD-ADM. Of the five patients, one patient
      with ILD-PM and one patient with ILD-ADM survived. No adverse reactions were seen
      due to IVIG treatment. There were no critical differences in the clinical
      parameters and clinical courses between survivors and nonsurvivors. IVIG
      treatment is safe and could be an effective salvage therapy for refractory ILD
      PM/DM in certain cases, suggesting that further controlled trials are worthwhile.

PMID- 19387737
TI  - Successful treatment of pulmonary aspiration due to brain stem infarction by
      using cough exercise based on swallowing scintigraphy: preliminary observations.
AB  - Although dysphagia in stroke may result in lethal chest infection, it can be
      prevented by coughing. We report on a patient with dysphagia and aspiration who
      regained oral ingestion by swallowing with voluntary cough. A 54-year-old man
      with subarachnoidal hemorrhage underwent endovascular coiling and developed brain
      stem infarction. Scintigraphy showed pulmonary aspiration just after swallowing,
      but no radioactivity was detected in the lungs 10 min after swallowing with
      voluntary cough. Swallowing exercise with voluntary cough resulted in a safe
      swallow without enteral feeding. Even if laryngeal penetration and pulmonary
      aspiration are observed, chest infection could be prevented by swallowing
      exercise combined with voluntary cough.

PMID- 19387738
TI  - From the editor's desk.

PMID- 19387739
TI  - Letter to the editor re: Voice recognition dictation: radiologist as
      transcriptionist and Improvement of report workflow and productivity using speech
      recognition--a follow-up study.

PMID- 19387740
TI  - Should radiology IT be owned by the chief information officer?
AB  - Considerable debate within the medical community has focused on the optimal
      location of information technology (IT) support groups on the organizational
      chart. The challenge has been to marry local accountability and physician
      acceptance of IT with the benefits gained by the economies of scale achieved by
      centralized knowledge and system best practices. In the picture archiving and
      communication systems (PACS) industry, a slight shift has recently occurred
      toward centralized control. Radiology departments, however, have begun to realize
      that no physicians in any other discipline are as dependent on IT as radiologists
      are on their PACS. The potential strengths and weaknesses of centralized control
      of the PACS is the topic of discussion for this month's Point/Counterpoint.

PMID- 19387741
TI  - Surgical treatment of resectable and borderline resectable pancreas cancer:
      expert consensus statement.

PMID- 19387742
TI  - Long-term survival in patients with pseudomyxoma peritonei treated with
      cytoreductive surgery and perioperative intraperitoneal chemotherapy: 10 years of
      experience from a single institution.
AB  - BACKGROUND: Cytoreductive surgery (CRS) and perioperative intraperitoneal
      chemotherapy (PIC) has been recognized as a treatment option for pseudomyxoma
      peritonei. This study reports the survival outcomes, clinicopathological
      prognostic factors, and a learning curve from a single institution's experience.
      METHODS: Patients with pseudomyxoma peritonei underwent CRS and PIC, which was
      comprised of hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early
      postoperative intraperitoneal chemotherapy (EPIC), according to a standardized
      treatment protocol in our institution. Clinicopathological factors were analyzed
      to determine their prognostic value for survival using univariate and
      multivariate analysis. Time period comparison was performed to study the effect
      of a learning curve. RESULTS: A total of 106 patients (43 men and 63 women) were
      treated. The mortality rate was 3% and severe morbidity rate was 49%. The median
      follow-up was 23 (range, 0-140) months. The overall median survival was 104
      months with a 5-year survival rate of 75%. The progression-free survival was 40
      months with a 1-year progression-free survival rate of 71%. Factors influencing
      survival include histopathological type of tumor, use of both HIPEC and EPIC,
      peritoneal cancer index, completeness of cytoreduction, and severe morbidity. The
      results demonstrate a learning curve where patients with a higher peritoneal
      cancer index (PCI) were treated, reduced amount of blood products required, more
      patients undergoing HIPEC and the combined HIPEC and EPIC, more redo-procedures
      performed, and a longer progression-free survival. CONCLUSIONS: This report
      demonstrates long-term survival outcomes, acceptable perioperative outcomes, and
      a learning curve associated with the treatment of patients with pseudomyxoma
      peritonei.

PMID- 19387743
TI  - Dynamic coexistence of sexual and asexual invasion fronts in a system of integro
      difference equations.
AB  - The role of long-range dispersal in the coexistence of sexual and asexual
      relatives in a population of hermaphrodite flowering plants is investigated. In
      these populations, growth and reproduction often occur during a sedentary stage
      that is then followed by dispersal of propagules. These two stages are clearly
      distinguishable and show strong seasonality. A modeling approach that accurately
      describes this kind of dynamics of mixed populations is a system of two nonlinear
      integro-difference equations. It is shown that this kind of model can accommodate
      coexistence of the two different reproductive types.

PMID- 19387744
TI  - Stochastic models and numerical algorithms for a class of regulatory gene
      networks.
AB  - Regulatory gene networks contain generic modules, like those involving feedback
      loops, which are essential for the regulation of many biological functions (Guido
      et al. in Nature 439:856-860, 2006). We consider a class of self-regulated genes
      which are the building blocks of many regulatory gene networks, and study the
      steady-state distribution of the associated Gillespie algorithm by providing
      efficient numerical algorithms. We also study a regulatory gene network of
      interest in gene therapy, using mean-field models with time delays. Convergence
      of the related time-nonhomogeneous Markov chain is established for a class of
      linear catalytic networks with feedback loops.

PMID- 19387745
TI  - The evolutionary reduction principle for linear variation in genetic
      transmission.
AB  - The evolution of genetic systems has been analyzed through the use of modifier
      gene models, in which a neutral gene is posited to control the transmission of
      other genes under selection. Analysis of modifier gene models has found the
      manifestations of an "evolutionary reduction principle": in a population near
      equilibrium, a new modifier allele that scales equally all transition
      probabilities between different genotypes under selection can invade if and only
      if it reduces the transition probabilities. Analytical results on the reduction
      principle have always required some set of constraints for tractability:
      limitations to one or two selected loci, two alleles per locus, specific
      selection regimes or weak selection, specific genetic processes being modified,
      extreme or infinitesimal effects of the modifier allele, or tight linkage between
      modifier and selected loci. Here, I prove the reduction principle in the absence
      of any of these constraints, confirming a twenty-year-old conjecture. The proof
      is obtained by a wider application of Karlin's Theorem 5.2 (Karlin in
      Evolutionary biology, vol. 14, pp. 61-204, Plenum, New York, 1982) and its
      extension to ML-matrices, substochastic matrices, and reducible matrices.

PMID- 19387746
TI  - How well do guidelines incorporate evidence on patient preferences?
AB  - BACKGROUND: Clinical practice guidelines (CPG) are meant to consider important
      values such as patient preferences. OBJECTIVE: To assess how well clinical
      practice guidelines (CPGs) integrate evidence on patient preferences compared
      with that on treatment effectiveness. DESIGN: A cross-sectional review of a
      listing in 2006 of CPGs judged to be the best in their fields by an external
      joint government and medical association body. STUDY SELECTION: Exclusion
      criterion was unavailability in electronic format. Sixty-five of 71 listed CPGs
      met selection criteria. MEASUREMENTS: Two instruments originally constructed to
      evaluate the overall quality of CPGs were adapted to specifically assess the
      quality of integrating information on patient preference vs. treatment
      effectiveness. Counts of words and references in each CPG associated with patient
      preferences vs. treatment effectiveness were performed. Two reviewers
      independently assessed each CPG. MAIN RESULTS: Based on our adapted instruments,
      CPGs scored significantly higher (p < 0.001) on the quality of integrating
      treatment effectiveness compared with patient preferences evidence (mean
      instrument one scores on a scale of 0.25 to 1.00: 0.65 vs. 0.43; mean instrument
      two scores on a scale of 0 to 1: 0.58 vs. 0.18). The average percentage of the
      total word count dedicated to treatment effectiveness was 24.2% compared with
      4.6% for patient preferences. The average percentage of references citing
      treatment effectiveness evidence was 36.6% compared with 6.0% for patient
      preferences. CONCLUSION: High quality CPGs poorly integrate evidence on patient
      preferences. Barriers to incorporating preference evidence into CPGs should be
      addressed.

PMID- 19387747
TI  - The risks of rewards in health care: how pay-for-performance could threaten, or
      bolster, medical professionalism.

PMID- 19387748
TI  - Process of care failures in breast cancer diagnosis.
AB  - BACKGROUND: Process of care failures may contribute to diagnostic errors in
      breast cancer care. OBJECTIVE: To identify patient- and provider-related process
      of care failures in breast cancer screening and follow-up in a non-claims-based
      cohort. DESIGN: Retrospective chart review of a cohort of patients referred to
      two Boston cancer centers with new breast cancer diagnoses between January 1,
      1999 and December 31, 2004. PARTICIPANTS: We identified 2,275 women who reported
      > or =90 days between symptom onset and breast cancer diagnosis or presentation
      with at least stage II disease. We then selected the 340 (14.9%) whose physicians
      shared an electronic medical record. We excluded 238 subjects whose records were
      insufficient for review, yielding a final cohort of 102 patients. INTERVENTIONS:
      None MEASUREMENTS: We tabulated the number and types of process of care failures
      and examined risk factors using bivariate analyses and multivariable Poisson
      regression. MAIN RESULTS: Twenty-six of 102 patients experienced > or =1 process
      of care failure. The most common failures occurred when physicians failed to
      perform an adequate physical examination, when patients failed to seek care, and
      when diagnostic or laboratory tests were ordered but patients failed to complete
      them. Failures were attributed in similar numbers to provider- and patient
      related factors (n = 30 vs. n = 25, respectively). Process of care failures were
      more likely when the patient's primary care physician was male (IRR 2.8, 95% CI
      1.2 to 6.5) and when the patient was non-white (IRR 2.8, 95% CI 1.4 to 5.7).
      CONCLUSIONS: Process failures were common in this patient cohort, with both
      clinicians and patients contributing to breakdowns in the diagnostic process.

PMID- 19387753
TI  - Abstracts of the 2009 In Vitro Biology Meeting. June 6-10, 2009. Charleston,
      South Carolina, USA.

PMID- 19387750
TI  - Racial and ethnic differences in preferences for end-of-life treatment.
AB  - BACKGROUND: Studies using local samples suggest that racial minorities anticipate
      a greater preference for life-sustaining treatment when faced with a terminal
      illness. These studies are limited by size, representation, and insufficient
      exploration of sociocultural covariables. OBJECTIVE: To explore racial and ethnic
      differences in concerns and preferences for medical treatment at the end of life
      in a national sample, adjusting for sociocultural covariables. DESIGN: Dual
      language (English/Spanish), mixed-mode (telephone/mail) survey. PARTICIPANTS: A
      total of 2,847 of 4,610 eligible community-dwelling Medicare beneficiaries age 65
      or older on July 1, 2003 (62% response). MEASUREMENTS: Demographics, education,
      financial strain, health status, social networks, perceptions of health-care
      access, quality, and the effectiveness of mechanical ventilation (MV), and
      concerns and preferences for medical care in the event the respondent had a
      serious illness and less than 1 year to live. RESULTS: Respondents included 85%
      non-Hispanic whites, 4.6% Hispanics, 6.3% blacks, and 4.2% "other"
      race/ethnicity. More blacks (18%) and Hispanics (15%) than whites (8%) want to
      die in the hospital; more blacks (28%) and Hispanics (21.2%) than whites (15%)
      want life-prolonging drugs that make them feel worse all the time; fewer blacks
      (49%) and Hispanics (57%) than whites (74%) want potentially life-shortening
      palliative drugs, and more blacks (24%, 36%) and Hispanics (22%, 29%) than whites
      (13%, 21%) want MV for life extension of 1 week or 1 month, respectively. In
      multivariable analyses, sociodemographic variables, preference for specialists,
      and an overly optimistic belief in the effectiveness of MV explained some of the
      greater preferences for life-sustaining drugs and mechanical ventilation among
      non-whites. Black race remained an independent predictor of concern about
      receiving too much treatment [adjusted OR = 2.0 (1.5-2.7)], preference for dying
      in a hospital [AOR = 2.3 (1.6-3.2)], receiving life-prolonging drugs [1.9 (1.4
      2.6)], MV for 1 week [2.3 (1.6-3.3)] or 1 month's [2.1 (1.6-2.9)] life extension,
      and a preference not to take potentially life-shortening palliative drugs [0.4
      (0.3-0.5)]. Hispanic ethnicity remained an independent predictor of preference
      for dying in the hospital [2.2 (1.3-4.0)] and against potentially life-shortening
      palliative drugs [0.5 (0.3-0.7)]. CONCLUSIONS: Greater preference for intensive
      treatment near the end of life among minority elders is not explained fully by
      confounding sociocultural variables. Still, most Medicare beneficiaries in all
      race/ethnic groups prefer not to die in the hospital, to receive life-prolonging
      drugs that make them feel worse all the time, or to receive MV.

PMID- 19387761
TI  - Remote cell death in the cerebellar system.
AB  - Functional impairment after focal CNS lesion is highly dependent on damage that
      occurs in regions that are remote but functionally connected to the primary
      lesion site. This pattern is particularly evident in the cerebellar system, in
      which functional interactions between the cerebellar cortex, deep cerebellar
      nuclei, and precerebellar stations are of paramount importance. Diffuse
      degeneration after development of a focal CNS lesion has been associated with
      poor outcomes in several pathologies, such as stroke, multiple sclerosis, and
      brain trauma. A greater understanding of the mechanisms that underlie the spread
      of death signals from focal lesions, however, can aid in identifying a
      neuroprotective approach for CNS pathologies. To this end, studies on
      degenerative mechanisms in the inferior olive and pontine nuclei after focal
      cerebellar damage have been a valuable asset in which pharmacological approaches
      have been tested. In this review, we focus on mechanisms of remote cell death in
      cerebellar circuits, analyzing the neuroprotective effects of inflammation
      modulating drugs in particular.

PMID- 19387762
TI  - Witnessing ischemia or proofing coronary atherosclerosis: two different windows
      on the same or on different pathways precipitating cardiovascular events?
AB  - Risk stratification and prevention of future cardiac events is an extremely
      relevant part of the daily medical practice in the large population of
      asymptomatic or scarcely symptomatic patients. The strategies available to this
      purpose encompass programs intended either to reduce progression and
      complications of atherosclerosis, and revascularization procedures aimed to
      reduce total ischemic burden. The former represents a primary prevention approach
      and fights the substrate of ischemic heart disease. The latter, instead, is used
      to reduce the total ischemic burden and thus implies to identify those patients
      in whom ischemia can be life threatening because of its severity and extension.
      Today, at least two imaging methods are available for this task: coronary calcium
      scoring by x-ray CT and ischemia assessment by myocardial perfusion imaging.
      Although both approaches can accurately estimate cardiovascular risk, from a
      theoretical point of view, the assessment of ischemia evaluates the functional
      consequences of coronary obstructions and thus the target of revascularization
      procedure, while estimating the total atherosclerotic burden represents an
      indirect index of it. This difference might appear academic in its nature, given
      the current model of ischemic heart disease pathophysiology that assumes and
      predicts a very tight correlation between the severity of a coronary stenosis and
      its capability to cause ischemia. However, the majority of studies focused on the
      combined risk assessment with both approaches confirm the relevance of this
      issue. In fact, among 7785 patients reported in the literature, coronary calcium
      scoring most often resulted in positive findings (78%). However, this sign of
      atherosclerosis was associated with inducible ischemia in only one-fifth of
      patients. In the near future, coronary calcium scoring will be easily and
      immediately completed by the noninvasive definition of coronary stenoses. At that
      time we will face a still largely unknown risk: the presence of a stenosis in the
      absence of symptoms and of ischemia. Evaluating the effectiveness of different
      protocols will thus be needed to improve our capability to help these patients.

PMID- 19387763
TI  - Tracking of size-adjusted bone mineral content and bone area in boys and girls
      from 10 to 17 years of age.
AB  - Positive correlations for bone mineral content (BMC) between 10 and 17 years of
      age were found for boys and girls after adjusting for body size, puberty, and
      diet. This tracking of BMC indicated that osteoporosis prevention should begin
      already in prepuberty. INTRODUCTION: Previous studies indicate that BMC is
      tracking during growth, but it remains unclear whether this would remain
      significant after adjusting for important confounders. We tested the hypothesis
      that BMC and bone area (BA) track from 10 to 17 years of age, independently of
      body size, pubertal stage, and dietary intake of energy, calcium and protein.
      METHODS: A longitudinal study where whole body (T) and lumbar spine (LS) BMC and
      BA (dual-energy X-ray absorptiometry) and dietary intake (7-day food records)
      were assessed at 10 and 17 years of age in boys and girls (n = 91). Tracking of
      bone variables from 10 to 17 years was estimated by Pearson's correlations
      adjusted for the selected confounders. RESULTS: The unadjusted correlations for T
      BMC between 10 and 17 years, likewise for LS-BMC and T-BA, were positive for both
      sexes (0.51-0.81; P < 0.0001) and remained significant after correcting for the
      selected confounders. The unadjusted correlations for LS-BA between 10 and 17
      years were significant only for girls (0.29; P < 0.05), but not after further
      corrections. CONCLUSIONS: Bone mass tracks from 10 to 17 years of age in boys and
      girls, especially after accounting for important confounders, indicating that
      osteoporosis prevention should begin in early stages of bone development.

PMID- 19387764
TI  - Bone fragility in male glucocorticoid-induced osteoporosis is not defined by bone
      mineral density.
AB  - Eighty-seven male Japanese subjects taking prednisolone > or = 5 mg for more than
      6 months and 132 age- and body mass index (BMI)-matched control subjects were
      examined. Multiple regression analysis adjusted for age and BMI showed that
      spinal bone mineral density (BMD) in the prednisolone group was not associated
      with prevalent vertebral fractures (VFs). INTRODUCTION: Glucocorticoid (GC)
      treatment is known to increase the risk for bone fractures. However, the
      association between VFs and BMD in GC-treated male patients remains unclear.
      METHODS: Eighty-seven male subjects taking prednisolone > or = 5 mg for more than
      6 months and 132 age- and BMI-matched control subjects were examined using
      lateral thoracic and lumbar spine radiographs and spine dual energy X-ray
      absorptiometry. RESULTS: The presence of GC use was an independent risk factor
      for VFs adjusted for age and BMI (odds ratio 10.93, P < 0.001). By receiver
      operating characteristic analysis, the absolute BMD values for detecting VFs were
      higher and the sensitivity and specificity were lower in the GC group than in the
      control group (0.936 vs 0.825 g/cm(2) and 53.5% vs 74.0%, respectively). Multiple
      regression analysis adjusted for age and BMI showed that spinal BMD in the GC
      group was not associated with prevalent VFs, even after adding current and past
      maximum GC doses as independent variables. CONCLUSIONS: These results show that
      lumbar BMD values are not associated with prevalent VFs in GC-treated male
      patients, suggesting that bone fragility in male GC users is affected by bone
      quality rather than by BMD.

PMID- 19387765
TI  - Concomitant diseases in a cohort of patients with idiopathic myositis during long
      term follow-up.
AB  - This study aims to report the concomitant diseases observed and damage outcome in
      a cohort of patients with adult idiopathic inflammatory myositis (IIM) during
      long-term follow-up. All patients with IIM were identified from a single centre
      (follow-up between 1979 and 2006) and fulfilled at least three of the four Bohan
      and Peter criteria. Patients with inclusion body myositis, juvenile-onset
      myositis and overt overlap syndromes were excluded. Medical notes were
      retrospectively reviewed. Concomitant diseases identified were divided into 12
      different organ systems (bone, cardiac, respiratory, gastrointestinal, renal,
      central nervous, malignancy, infection, endocrine, eyes, dermatological and
      haematological). Patient damage index was calculated using the Myositis Damage
      Index tool. Fifty-five patients (31 polymyositis, 24 dermatomyositis) were
      identified. The most prevalent organ system involved was lung with 40 events per
      1,000 patient years follow-up. There was significant steroid-related
      complications with 17/18 patients with bone involvement having
      osteopenia/osteoporosis. Sjogren's syndrome (n = 3) was the most frequent
      concomitant auto-immune disease observed. Patients with a higher number of organ
      systems involved had a significantly higher damage index (r = 0.48, p = 0.001).
      White patients showed a significant trend to develop more than three other organ
      system involvement (p < 0.0001) and myositis-related lung disease (p < 0.0001)
      compared to other races. There is significant steroid-related morbidity in adult
      IIM patients under long-term follow-up. The prevalence of another concomitant
      auto-immune disease unlike patients with lupus or Sjogren's syndrome is low.

PMID- 19387766
TI  - Changes in the bacterial populations of the highly alkaline saline soil of the
      former lake Texcoco (Mexico) following flooding.
AB  - Flooding an extreme alkaline-saline soil decreased alkalinity and salinity, which
      will change the bacterial populations. Bacterial 16S rDNA libraries were
      generated of three soils with different electrolytic conductivity (EC), i.e. soil
      with EC 1.7 dS m(-1) and pH 7.80 (LOW soil), with EC 56 dS m(-1) and pH 10.11
      (MEDIUM soil) and with EC 159 dS m(-1) and pH 10.02 (HIGH soil), using universal
      bacterial oligonucleotide primers, and 463 clone 16S rDNA sequences were analyzed
      phylogenetically. Library proportions and clone identification of the phyla
      Proteobacteria, Actinobacteria, Acidobacteria, Cyanobacteria, Bacteroidetes,
      Firmicutes and Cloroflexi showed that the bacterial communities were different.
      Species and genera of the Rhizobiales, Rhodobacterales and Xanthomonadales orders
      of the alpha- and gamma-subdivision of Proteobacteria were found at the three
      sites. Species and genera of the Rhodospirillales, Sphingobacteriales,
      Clostridiales, Oscillatoriales and Caldilineales were found only in the HIGH
      soil, Sphingomonadales, Burkholderiales and Pseudomonadales in the MEDIUM soil,
      Myxococcales in the LOW soil, and Actinomycetales in the MEDIUM and LOW soils. It
      was found that the largest diversity at the order and species level was found in
      the MEDIUM soil as bacteria of both the HIGH and LOW soils were found in it.

PMID- 19387767
TI  - Physicians make different decisions from nephrologists at serum creatinine 2.0
      mg/dl.
AB  - BACKGROUND: It is very important, but not clear, how physicians differ from
      nephrologists in treatment of renal insufficiency. AIM: To demonstrate
      differences in decision-making in treatment of renal insufficiency between
      physicians and nephrologists. DESIGN OF STUDY: Postal questionnaire. SETTING: All
      physicians were graduates from one medical school and certified by the Japanese
      Society of Internal Medicine. Nephrologists were certified by the Society and the
      Japanese Society of Nephrology. METHOD: Questionnaires were sent to 1,395
      physicians and 385 nephrologists, including audit of serum creatinine
      concentration that would indicate referral to nephrologist, audit of continuation
      of angiotensin converting enzyme inhibitor (ACEI) for a case of renal
      insufficiency and mild hyperkalemia due to ACEI. Outputs were proportion that
      selected "serum creatinine 177 micromol/l (2.0 mg/dl) and over" as a referral
      point to the nephrologist, and proportion that chose "suspend ACEI" for a case of
      renal insufficiency and mild hyperkalemia due to ACEI. RESULTS: Six hundred and
      fourteen physicians replied (44%), and 111 certified in internal medicine were
      extracted from them. One hundred and eighty-six certified nephrologists replied
      (47%), and 114 certified in internal medicine were extracted. The proportion that
      chose "177 micromol/l" as a referral point to the nephrologist was 20% for
      physicians and 61% for nephrologists (P < 0.0001). An additional 17% of
      nephrologists recommended creatinine concentration below 177 micromol/l, whereas
      no such opinion was found among physicians. The proportion that chose "suspend
      ACEI" was 45% for physicians and 16% for nephrologists (P < 0.0001). CONCLUSION:
      There is significant difference between decisions made by physicians and
      nephrologists regarding treatment for patients with serum creatinine
      concentration of 177 micromol/l.

PMID- 19387768
TI  - Antinociceptive, antipyretic, and anti-inflammatory activities of Putranjiva
      roxburghii Wall. leaf extract in experimental animals.
AB  - The effects of the ether extract from the leaves of Putranjiva roxburghii (P.
      roxburghii) Wall. were assessed on nociceptive responses in mice by using
      writhing, hot plate, and formalin tests and the antipyretic activity was
      determined in yeast-induced fever in rats. Anti-inflammatory activities were also
      investigated using carrageenin-induced paw edema in rats and croton oil-induced
      ear and anus edemas. The ether extract (100, 200, and 400 mg/kg, p.o.) of P.
      roxburghii dose-dependently produced analgesic activity in acetic acid-induced
      writhing in mice. The extract had no significant effect in the hot plate test in
      mice. At the dose of 400 mg/kg, the extract significantly suppressed the licking
      activity in the late phase of the formalin test in mice and decreased fever
      induced by yeast in rats. The extract exhibited moderate inhibitory activity of
      inflammation in carrageenin-induced paw edema in rats. The extract inhibited
      croton oil-induced ear edema in a dose-dependent manner (1.25, 2.5, and 5.0
      mg/ear) in mice. The extract decreased anus edema induced by croton oil at the
      high dose of 800 mg/kg in rats. The results indicated that the ether extract of
      P. roxburghii leaves possesses analgesic, antipyretic, and anti-inflammatory
      activities.

PMID- 19387769
TI  - Hydroxychavicol: a potent xanthine oxidase inhibitor obtained from the leaves of
      betel, Piper betle.
AB  - The screening of Piperaceous plants for xanthine oxidase inhibitory activity
      revealed that the extract of the leaves of Piper betle possesses potent activity.
      Activity-guided purification led us to obtain hydroxychavicol as an active
      principle. Hydroxychavicol is a more potent xanthine oxidase inhibitor than
      allopurinol, which is clinically used for the treatment of hyperuricemia.

PMID- 19387770
TI  - Comparison of exercise-rest-reinjection Tl-201 imaging and rest sublingual
      isosorbide dinitrate Tc-99m MIBI imaging for the assessment of myocardial
      viability.
AB  - PURPOSE: Nitrate administration has been proposed to enhance the detection of
      myocardial viability when performing myocardial perfusion imaging. In this study,
      we aimed to compare Tl-201 exercise-rest-reinjection protocol with rest
      isosorbide dinitrate (ISDN)-Tc99m MIBI study in the same population examined for
      the myocardial viability. METHODS: Twenty-six patients with coronary artery
      disease who had fixed segmental defects on exercise-rest-Tl-201 imaging were
      studied. All of them underwent Tl-201 reinjection study. Within 1 week of Tl-201
      imaging, rest-Tc99m MIBI imaging was performed after sublingual 5 mg ISDN
      administration (2-day protocol). For each study, tomograms were divided into 20
      segments based on three short-axis slices, one vertical long-axis representing
      the totality of the left ventricle and regional tracer uptake was quantitatively
      analyzed. Regional tracer uptake was evaluated in 20 myocardial segments for all
      patients. Viability was defined as presence of tracer uptake >/=50% of peak
      activity on each study. A total 520 myocardial segments were assessed by semi
      quantitative analysis. RESULT: On the baseline rest Tl-201 studies, 211 segments
      of the 520 segments that were analyzed had <50% of peak activity. Of these
      segments, 42 (20%) showed reversibility after reinjection Tl-201 imaging and 55
      segments (27%) described as viable on the rest ISDN-Tc99m MIBI imaging. There was
      89% concordance between the ISDN-Tc99m MIBI study and Tl-201 reinjection study
      regarding viable myocardial segments. Of the 23 segments with discordant results,
      18 were irreversible on Tl-201 reinjection study, but showed >/=50% uptake on
      ISDN-Tc99m MIBI. CONCLUSION: Observation of good agreement between Tl-201
      reinjection and ISDN-Tc99m MIBI study studies led us to suggest the use of ISDN
      enhanced imaging in the evaluation of myocardial viability.

PMID- 19387771
TI  - Nesidioblastosis as a cause of focal pancreatic 111In-pentetreotide uptake in a
      patient with putative VIPoma: another differential diagnosis.
AB  - In adults, nesidioblastosis is a very infrequent condition and a rare cause of
      symptomatic presentations. The diagnosis of nesidioblastosis may be difficult
      with functional and anatomical imaging modalities. "Slight focal" pancreatic
      abnormalities using (111)In-pentetreotide imaging has been reported in patients
      with hyperinsulinaemic hypoglycaemia, confirmed histologically as
      nesidioblastosis. We describe a 60-year-old man who presented with a 1-year
      history of intermittent faecal urgency and refractory diarrhoea, non-specific
      laboratory results, negative imaging results (CT, MRI and EUS), a FNA biopsy that
      was inconclusive, but suggested an endocrine cell neoplasm, and a (111)In
      pentetreotide scan that showed a moderately intense focal uptake clearly
      localised to the pancreatic head on a low-dose fusion CT. The histopathology of
      the specimen confirmed the diagnosis of nesidioblastosis.

PMID- 19387772
TI  - Association of differential and site-dependent CpG methylation and diverse
      expression of DNA methyltransferases with the tissue-specific expression of human
      beta-globin gene in transgenic mice.
AB  - Expression of human locus control region (LCR) and beta-globin promoter has been
      recognized as an important factor in time- and tissue-specific expression event.
      DNA methylation can affect the transcriptional activity of specific genes. To
      investigate the methylation mechanism in the regulation of LCR and promote
      expression, this study used a transgenic mouse strain generated previously, in
      which the hematopoietic-specific expression of the EGFP was driven by human beta
      globin promoter and under the control of LCR, to examine the CpG methylation
      pattern in various tissues. The results showed the inverse correlation between
      the methylated extent and the levels of gene expression in all tested tissues. We
      also found that the methylated extent of the 10 examined CpG sites was biased
      along their positions and is more efficient near the transcription start site.
      Real-time quantitative RT-PCR analysis of DNA methyltransferases (DNMTs)
      transcripts showed that Dnmt3a and Dnmt3b expressed with a very low level in the
      hematopoietic tissues that was coincident with the relative higher EGFP
      expression in these tissues, indicating that the differential expression of DNMTs
      contributed to the tissue-specific methylated patterns which caused the diverse
      gene expression in various tissues. These findings provide significant clues to
      elucidate the mechanism of the regulation on tissue-specific expression of genes.

PMID- 19387774
TI  - Atypical presentation of acute myeloid leukemia: cardiac myeloid sarcoma.
AB  - We present the case of a 52-year-old man with a 2-month history of dyspnea,
      bilateral pleural effusion and cardiomegaly of rapid onset. A cardiac ultrasound
      showed pericardial effusion with infiltration of the infero-lateral cardiac wall,
      right auricle and aortic arch by a mass of unknown origin. Despite 1% blast cells
      in the peripheral blood, 2 bone marrow biopsies were negative for malignancy.
      Flow cytometry analysis of the blood and immunohistochemistry study of the
      pleural liquid showed a blast population of CD34+, CD33+, CD13+ and HLA-DR+
      cells; a percutaneous cardiac biopsy showed CD34+ cells in the pericardium which
      led to the diagnosis of extramedullary acute myeloid leukemia (AML). The patient
      was treated with induction chemotherapy allowing remission, but unfortunately
      died of septic shock of fungal origin. This case illustrates a rare presentation
      of cardiac extramedullary AML.

PMID- 19387775
TI  - Malignant neoplasm in the axilla of a male: suspected primary carcinoma of an
      accessory mammary gland.
AB  - A 58-year-old Japanese male patient visited our hospital for evaluation of an
      elastic hard mass, measuring 80 x 50 mm, in the right axillary area. Incisional
      biopsy for suspected malignancy was performed, and histopathologic examination by
      hematoxylin-eosin (H&E) staining yielded a diagnosis of poorly differentiated
      adenocarcinoma metastatic from an unknown primary. As the tumor was
      immunohistochemically positive for both ER and PgR, metastatic breast cancer was
      strongly suspected. Ultrasonography, CT, and MRI revealed no evidence of tumors
      in the bilateral mammary glands. Detailed examination of the head and neck
      region, lung, and upper and lower gastrointestinal tract also revealed no
      evidence of a primary tumor. After chemotherapy, the patient underwent tumor
      resection with axillary lymph node dissection. On the basis of the histological
      features of H&E-stained specimens and immunohistochemistry of the resected tumor,
      this case was diagnosed as breast cancer of unknown origin in a male. The tumor
      could have been an axillary lymph node metastasis from an occult breast
      carcinoma, or primary cancer arising in an accessory mammary gland.

PMID- 19387776
TI  - Estrogen receptor-beta status influences clinical outcome of triple-negative
      breast cancer.
AB  - In this conference paper, we show that estrogen receptor-beta status influences
      clinical outcome of triple-negative breast cancer referring two of our recent
      research articles.

PMID- 19387777
TI  - "Moving window" operation for breast-conserving surgery.
AB  - BACKGROUND: Although endoscope-assisted surgery has been used for partial
      mastectomy to improve the cosmetic outcome, this procedure may be somewhat
      cumbersome, thereby increasing operating time and blood loss. Moreover, the use
      of expensive disposable endoscopic instruments is required. METHODS: We have
      performed partial mastectomy via a small periareolar incision (transareolar
      approach) and/or axillary incision (transaxillary approach) using a wound
      retractor and bipolar scissors without disposable endoscopic instruments in 58
      patients with noninvasive or invasive breast cancer. Axillary lymph node
      dissection is also performed via small axillary incision using a wound retractor
      and bipolar scissors. RESULTS: Average surgical duration was 132 min in
      transareolar approach and 125 min in transaxillary approach. Average blood loss
      was 38 and 48 ml, respectively. Postoperatively, the margin of resected breast
      tissue was histologically confirmed to be negative in 56 of 58 patients (97%)
      patients. Postoperative appearance of conserved breast was excellent in many
      patients, unless a large volume of breast tissue was removed. CONCLUSION: A wound
      retractor provides maximum exposure with minimum incision size, thereby allows
      performance of breast-conserving surgery via a small periareolar and/or axillary
      incision in patients with a nipple-areola complex that is mobile and not small.
      It can reduce operating time and blood loss when compared with endoscope-assisted
      partial mastectomy.

PMID- 19387788
TI  - Computational analysis of the effect of the type of LVAD flow on coronary
      perfusion and ventricular afterload.
AB  - We developed a computational model to investigate the hemodynamic effects of a
      pulsatile left ventricular assist device (LVAD) on the cardiovascular system. The
      model consisted of 16 compartments for the cardiovascular system, including
      coronary circulation and LVAD, and autonomic nervous system control. A failed
      heart was modeled by decreasing the end-systolic elastance of the ventricle and
      blocking the mechanism controlling heart contractility. We assessed the
      physiological effect of the LVAD on the cardiovascular system for three types of
      LVAD flow: co-pulsation, counter-pulsation, and continuous flow modes. The
      results indicated that the pulsatile LVAD with counter-pulsation mode gave the
      most physiological coronary blood perfusion. In addition, the counter-pulsation
      mode resulted in a lower peak pressure of the left ventricle than the other
      modes, aiding cardiac recovery by reducing the ventricular afterload. In
      conclusion, these results indicate that, from the perspective of cardiovascular
      physiology, a pulsatile LVAD with counter-pulsation operation is a plausible
      alternative to the existing LVAD with continuous flow mode.

PMID- 19387789
TI  - Cloning of the genome of equine herpesvirus 4 strain TH20p as an infectious
      bacterial artificial chromosome.
AB  - Equine herpesvirus 4 (EHV-4) is a major cause of respiratory tract disease in
      horses worldwide. The generation of recombinant viruses, which would lead to
      understanding of viral gene functions, has been hindered by the absence of
      suitable cell lines and small-animal models of the infection. In the present
      study, the genome of EHV-4 strain TH20p was cloned as a stable and infectious BAC
      without any deletions of the viral genes. Mini F plasmid sequences flanked by
      loxP sites were inserted into the intergenic region between genes 58 and 59.
      Coinfection of the recombinant virus with a recombinant adenovirus expressing Cre
      recombinase resulted in the excision of the BAC sequences. Importantly, the
      resulting recombinant EHV-4 replicated comparably to the wild-type virus in fetal
      horse kidney cells. The recombinant EHV-4 will facilitate EHV-4 research and
      provide the opportunity to exploit the power of BAC technology for production of
      recombinant viral vaccines.

PMID- 19387790
TI  - Predicting protein-protein interactions from sequence using correlation
      coefficient and high-quality interaction dataset.
AB  - Identifying protein-protein interactions (PPIs) is critical for understanding the
      cellular function of the proteins and the machinery of a proteome. Data of PPIs
      derived from high-throughput technologies are often incomplete and noisy.
      Therefore, it is important to develop computational methods and high-quality
      interaction dataset for predicting PPIs. A sequence-based method is proposed by
      combining correlation coefficient (CC) transformation and support vector machine
      (SVM). CC transformation not only adequately considers the neighboring effect of
      protein sequence but describes the level of CC between two protein sequences. A
      gold standard positives (interacting) dataset MIPS Core and a gold standard
      negatives (non-interacting) dataset GO-NEG of yeast Saccharomyces cerevisiae were
      mined to objectively evaluate the above method and attenuate the bias. The SVM
      model combined with CC transformation yielded the best performance with a high
      accuracy of 87.94% using gold standard positives and gold standard negatives
      datasets. The source code of MATLAB and the datasets are available on request
      under smgsmg@mail.ustc.edu.cn.

PMID- 19387791
TI  - Using K-minimum increment of diversity to predict secretory proteins of malaria
      parasite based on groupings of amino acids.
AB  - Due to the complexity of Plasmodium falciparumis genome, predicting secretory
      proteins of P. falciparum is more difficult than other species. In this study,
      based on the measure of diversity definition, a new K-nearest neighbor method, K
      minimum increment of diversity (K-MID), is introduced to predict secretory
      proteins. The prediction performance of the K-MID by using amino acids
      composition as the only input vector achieves 88.89% accuracy with 0.78 Mathew's
      correlation coefficient (MCC). Further, the several reduced amino acids alphabets
      are applied to predict secretory proteins and the results show that the
      prediction results are improved to 90.67% accuracy with 0.83 MCC by using the 169
      dipeptide compositions of the reduced amino acids alphabets obtained from Protein
      Blocks method.

PMID- 19387793
TI  - Usefulness of simplified acute physiology score II in predicting mortality in
      patients admitted to an emergency medicine ward.
AB  - The Objective of this prospective observational study was to evaluate the
      applicability of the simplified acute physiology score (SAPS II) in patients
      admitted to an Emergency Medicine Ward in the Emergency Medicine Ward of a
      tertiary university hospital. We studied consecutive patients admitted to an
      Emergency Medicine Ward from the emergency department. The SAPS II was assessed
      in predicting overall in-hospital mortality in terms of sensitivity, specificity
      and receiver operating characteristic (ROC) curve. A total of 211 consecutive
      patients were admitted over a period of 2 months. Median SAPS II score was 28
      (range 6-93), with a mean risk of in-hospital mortality of 0.17 (range 0.01-0.97)
      for the whole population, and an observed mortality of 15%. The area under the
      receiver operator curve (ROC) was 0.84 (0.77-0.91). Considering a cut-off value
      of SAPS II of 49, the sensitivity was 0.50 (95% CI 0.42-0.56), the specificity
      was 0.95 (0.92-0.98), the positive predictive value (PPV) was 0.64 (0.58-0.71),
      and the negative predictive value (NPV) was 0.91 (0.87-0.95), the positive
      likelihood ratio (pLH) was 9.9, and the negative likelihood ratio (nLH) was 0.5.
      If contrarily a cut-off value of SAPS II of 22 were used, the sensitivity would
      be 1.0, the specificity would be 0.21 (0.16-0.26), the PPV would be 0.18 (0.13
      0.23), the NPV would be 1.0, the pLH would be 1.3, and the nLH would be 0.0. In
      this preliminary study, SAPS II predicted in-hospital mortality in patients
      admitted to an Emergency Ward.

PMID- 19387792
TI  - Prevalence of migraine and tension-type headache among adults in Jordan.
AB  - Here, we investigated the prevalence of headache among adults in Jordan. The
      study was conducted from January 2007 to November 2008. A sample of 4,836
      participants were permitted to complete a self-conducted screening questionnaire.
      As much as 82.3% of participants complained from headache at least once per year.
      36.1% were tension-type headache and 59% of the participants had other family
      members who suffered from headache. Headaches affected everyday activities in
      51.6% of the participants; 82.7% of participants did not seek medical attention
      for their headaches. Among those who used analgesics (75.6%), acetaminophen was
      the most common (91.43%). In conclusion, headache and overuse of analgesics were
      prevalent in a significant part of the society. Thus, there is a need to educate
      the public to ensure safe practices and to make the use and selling of analgesics
      more stringent.

PMID- 19387794
TI  - What does the Italian population think about colorectal screening?

PMID- 19387795
TI  - The mammalian Nm23/NDPK family: from metastasis control to cilia movement.
AB  - Nucleoside diphosphate kinases (NDPK) are encoded by the NME genes, also called
      NM23. They catalyze the transfer of gamma-phosphate from nucleoside triphosphates
      to nucleoside diphosphates by a ping-pong mechanism involving the formation of a
      high energy phospho-histidine intermediate [1, 2]. Besides their known functions
      in the control of intracellular nucleotide homeostasis, they are involved in
      multiple physiological and pathological cellular processes such as
      differentiation, development, metastastic dissemination or cilia functions. Over
      the past 15 years, ten human genes have been discovered encoding partial, full
      length, and/or tandemly repeated Nm23/NDPK domains, with or without N-or C
      terminal extensions and/or additional domains. These genes encode proteins
      exhibiting different functions at various tissular and subcellular localizations.
      Most of these genes appear late in evolution with the emergence of the vertebrate
      lineage. This review summarizes the present knowledge on these multitalented
      proteins.

PMID- 19387796
TI  - Detection and analysis of protein histidine phosphorylation.
AB  - Protein histidine phosphorylation is well established as an important part of
      signalling systems in bacteria, fungi and plants and there is growing evidence of
      its role in mammalian cell biology. Compared to phosphoserine, phosphothreonine
      and phosphotyrosine, phosphohistidine is relatively labile, especially under the
      acidic conditions that were developed to analyse protein phosphorylation. In
      recent years, there has been an increasing impetus to develop specific methods
      for the analysis of histidine phosphorylation and assay of histidine kinase
      activity. Most recently attention has focussed on the application of mass
      spectrometry to this end. This review provides an overview of methods available
      for the detection and analysis of phosphohistidine in phosphoproteins, with
      particular emphasis on the application of mass spectrometric techniques.

PMID- 19387797
TI  - Clinical-translational strategies for the elevation of Nm23-H1 metastasis
      suppressor gene expression.
AB  - Interruption of the tumor metastatic process is a new, thought provoking
      molecular target for the treatment of cancer. The Nm23-H1 metastasis suppressor
      gene stands as a validated molecular target owing to its reduced expression in
      many aggressive human tumors, and the reduction in metastatic potential in vivo
      upon re-expression in multiple cell lines. Several compounds have been identified
      which elevate Nm23-H1 expression in vitro including indomethacin, gamma Linolenic
      Acid, trichostatin A, 5-aza-deoxycytidine, and high dose medroxyprogesterone
      acetate. Using a model of lung metastatic colonization by MDA-MB-231 human breast
      carcinoma cells, we demonstrated that high dose MPA reduced the formation of
      overt lung metastases by 37-46% and those metastases that formed were
      statistically smaller. A Phase II clinical trial of high dose MPA, alone or in
      combination with metronomic chemotherapy has recently opened.

PMID- 19387800
TI  - Diffusion studies of nanometer polymersomes across tissue engineered human oral
      mucosa.
AB  - PURPOSE: To measure the diffusion of nanometer polymersomes through tissue
      engineered human oral mucosa. METHODS: In vitro models of full thickness tissue
      engineered oral mucosa (TEOM) were used to assess the penetration properties of
      two chemically different polymersomes comprising two of block copolymers, PMPC
      PDPA and PEO-PDPA. These copolymers self-assemble into membrane-enclosed
      vesicular structures. Polymersomes were conjugated with fluorescent rhodamine in
      order to track polymersome diffusion. Imaging and quantification of the diffusion
      properties were assessed by confocal laser scanning microscopy (CLSM). RESULTS:
      TEOM is morphologically similar to natural oral mucosa. Using CLSM, both
      formulations were detectable in the TEOM within 6 h and after 48 h both
      penetrated up to 80 microm into the TEOM. Diffusion of PMPC-PDPA polymersomes was
      widespread across the epithelium with intra-epithelial uptake, while PEO-PDPA
      polymersomes also diffused into the epithelium. CONCLUSIONS: CLSM was found to be
      an effective and versatile method for analysing the level of diffusion of
      polymersomes into TEOM. The penetration and retention of PMPC-PDPA and PEO-PDPA
      polymersomes means they may have potential for intra-epithelial drug delivery
      and/or trans-epithelial delivery of therapeutic agents.

PMID- 19387801
TI  - Creating functional vesicle assemblies from vesicles and nanoparticles.
AB  - Vesicles (liposomes) have been shown to be excellent vehicles for drug delivery,
      yet assemblies of vesicles (vesicle aggregates) have been used infrequently in
      this context. However vesicle assemblies have useful properties not available to
      individual vesicles; their size can cause localisation in specific tissues and
      they can incorporate more functionality than is possible with individual
      vesicles. This article reviews progress on controlling the properties of vesicle
      assemblies in vitro, applications of vesicle assemblies in vivo, and our recent
      creation of magnetic nanoparticle-vesicle assemblies. The latter assemblies
      contain vesicles crosslinked by coated Fe3O4 nanoparticles and this inclusion of
      magnetic functionality makes them magnetically responsive, potentially allowing
      magnetically-induced contents release. This article describes further studies on
      the in vitro formation of these magnetic nanoparticle-vesicle assemblies,
      including the effect of changing magnetic nanoparticle concentration, pH,
      adhesive lipid structure and bilayer composition. These investigations have led
      to the development of thermally-sensitive magnetic nanoparticle-vesicle
      assemblies that release encapsulated methotrexate on warming.

PMID- 19387798
TI  - Dictyostelium discoideum--a model for many reasons.
AB  - The social amoeba or cellular slime mould Dictyostelium discoideum is a
      "professional" phagocyte that has long been recognized for its value as a
      biomedical model organism, particularly in studying the actomyosin cytoskeleton
      and chemotactic motility in non-muscle cells. The complete genome sequence of D.
      discoideum is known, it is genetically tractable, readily grown clonally as a
      eukaryotic microorganism and is highly accessible for biochemical, cell
      biological and physiological studies. These are the properties it shares with
      other microbial model organisms. However, Dictyostelium combines these with a
      unique life style, with motile unicellular and multicellular stages, and multiple
      cell types that offer for study an unparalleled variety of phenotypes and
      associated signalling pathways. These advantages have led to its recent emergence
      as a valuable model organism for studying the molecular pathogenesis and
      treatment of human disease, including a variety of infectious diseases caused by
      bacterial and fungal pathogens. Perhaps surprisingly, this organism, without
      neurons or brain, has begun to yield novel insights into the cytopathology of
      mitochondrial diseases as well as other genetic and idiopathic disorders
      affecting the central nervous system. Dictyostelium has also contributed
      significantly to our understanding of NDP kinase, as it was the Dictyostelium
      enzyme whose structure was first determined and related to enzymatic activity.
      The phenotypic richness and tractability of Dictyostelium should provide a
      fertile arena for future exploration of NDPK's cellular roles.

PMID- 19387802
TI  - Perceptions of type 1 diabetes among affected youth and their peers.
AB  - Management of type 1 diabetes (T1D) involves balancing several components
      including diet, exercise, and medication. Peer involvement in management tasks is
      an important, but understudied, issue in T1D. This study presents results of a
      preliminary examination of perceptions of disease management in youth with T1D
      and their peers. Data were collected using a mixed methods (qualitative and
      quantitative data) approach during medical education time at a camp for youth
      with T1D and their peers. Results suggest that both youth with T1D and their
      peers believe that peers need more information about medical consequences of
      having diabetes. Further, youth with T1D and their peers would like coaching on
      how peers may help the child with T1D manage their illness better. Results
      provide preliminary ideas for intervention (i.e., including peers, assessing
      social support) in the medical setting as well as ideas for future research
      (i.e., examining relationships among perceptions and gender, time since
      diagnosis).

PMID- 19387803
TI  - Modeling of tumor growth and anticancer effects of combination therapy.
AB  - Combination therapies are widely used in the treatment of patients with cancer.
      Selecting synergistic combination strategies is a great challenge during early
      drug development. Here, we present a pharmacokinetic/pharmacodynamic (PK/PD)
      model with a smooth nonlinear growth function to characterize and quantify
      anticancer effect of combination therapies using time-dependent data. To describe
      the pharmacological effect of combination therapy, an interaction term was
      introduced into a semi-mechanistic anticancer PK/PD model. This approach enables
      testing of a pharmacological hypothesis with respect to an anticipated
      pharmacological synergy of drug combinations, such as an assumed pharmacological
      synergy of complementary inhibition of a particular signaling pathway. The model
      was applied to three real data sets derived from preclinical screening
      experiments using xenograft mice. The suggested model fitted well the observed
      data from mono- to combination-therapy and allowed physiologically meaningful
      interpretation of the experiments. The tested drug combinations were assessed for
      their ability to act as synergistic modulators of tumor growth inhibition by the
      interaction parameter psi. The presented approach has practical implications
      because it can be applied to standard xenograft experiments and may assist in the
      selection of both optimal drug combinations and administration schedules. The
      unique feature of the presented approach is the ability to characterize the
      nature of combined drug interaction as well as to quantify the intensity of such
      interactions by assessing the time course of combined drug effect.

PMID- 19387804
TI  - Major hepatectomy induces phenotypic changes in circulating dendritic cells and
      monocytes.
AB  - INTRODUCTION: Patients undergoing major hepatectomy are at increased risk for
      post-operative morbidity and mortality, and changes in the phenotype of effector
      cells may predispose these patients to infectious sequelae. METHODS: To better
      understand post-hepatectomy immune responses, peripheral blood from 15
      hepatectomy patients was drawn immediately before and after liver resection and
      on post-operative days 1, 3, and 5. Circulating monocytes and dendritic cells
      were analyzed by flow cytometry for quantity, phenotype, activation status, human
      leukocyte antigen DR (HLA-DR) expression, and toll-like receptor-2 and -4
      expression. RESULTS: Major hepatectomy increased the numbers of activated
      CD16(bright) blood monocytes and the percentage of activated dendritic cells,
      although monocyte HLA-DR expression was reduced. These results may represent both
      dysfunctional antigen presentation and pending anergy, as well as cellular
      priming of immune effector cells. Better understanding of the alterations in
      innate immunity induced by hepatectomy may identify strategies to reduce
      infectious outcomes.

PMID- 19387805
TI  - Mitochondrial and cell-surface F0F1ATPsynthase in innate and acquired
      cardioprotection.
AB  - Mitochondria are central to heart function and dysfunction, and the pathways
      activated by different cardioprotective interventions mostly converge on
      mitochondria. In a context of perspectives in innate and acquired
      cardioprotection, we review some recent advances in F(0)F(1)ATPsynthase
      structure/function and regulation in cardiac cells. We focus on three topics
      regarding the mitochondrial F(0)F(1)ATPsynthase and the plasma membrane enzyme,
      i.e.: i) the crucial role of cardiac mitochondrial F(0)F(1)ATPsynthase regulation
      by the inhibitory protein IF(1) in heart preconditioning strategies; ii) the
      structure and function of mitochondrial F(0)F(1)ATPsynthase oligomers in
      mammalian myocardium as possible endogenous factors of mitochondria resistance to
      ischemic insult; iii) the external location and characterization of plasma
      membrane F(0)F(1) ATP synthase in search for possible actors of its regulation,
      such as IF(1) and calmodulin, at cell surface.

PMID- 19387806
TI  - Effects of Baicalin and Octreotide on the serum TNF-alpha level and apoptosis in
      multiple organs of rats with severe acute pancreatitis.
AB  - We investigated the effects of Baicalin and Octreotide on the levels of endotoxin
      and TNF-alpha in blood and the effects of apoptotic changes in multiple organs of
      SAP rats, and explored the underlying therapeutic mechanisms of Baicalin and
      Octreotide. In this study, 135 SAP rats were randomly divided into model control,
      Baicalin treated and Octreotide treated group (n = 45), respectively, the same
      number of normal rats were included in sham-operated group (n = 45). The above
      mentioned groups were further subdivided into 3, 6 and 12 h subgroups,
      respectively (15 rats in each subgroup). At 3, 6 and 12 h after operation, the
      mortality rate of rats, endotoxin and TNF-alpha levels in blood as well as the
      pathological severity scores, expression levels of Bax protein and apoptosis
      indexes in multiple organs were determined. Compared to model control group
      (1),both drugs can relieve the pathological injuries of multiple organs and
      decrease significantly the levels of endotoxin and TNF-alpha in blood and the
      mortality rate of rats in treated groups (P < 0.05 or P < 0.01); (2) the
      expression of Bax protein was upregulated in pancreas, lung, intestinal mucosa (P
      < 0.05 or P < 0.01) but downregulated in spleen and lymph nodes (P < 0.001 and P
      < 0.05, respectively) in Baicalin treated group; The apoptosis indexes
      significantly increased in pancreas, intestinal mucosa, lymph nodes and spleen (P
      < 0.05 or P < 0.01). (3) the expression of Bax protein was upregulated in
      pancreas and lung but downregulated in spleen and lymph nodes (P < 0.05 or P <
      0.01) in Octreotide treated group; The apoptosis indexes significantly increased
      in lymph nodes and spleen in Octreotide treated group (P < 0.05 or P < 0.01).
      Baicalin and Octreotide share a similar therapeutic efficacy in the treatment of
      SAP via a mechanism that is associated with inhibiting the levels of TNF-alpha in
      blood and induce apoptosis in multiple organs.

PMID- 19387807
TI  - Femoral vascular complications following catheter ablation of atrial
      fibrillation.
AB  - BACKGROUND: Femoral vascular complications remain a significant complication of
      catheter ablation of atrial fibrillation as a result of peri-procedural
      anticoagulation protocols. OBJECTIVE: We investigated the effect of three
      different anti-coagulation regimens on the incidence of femoral vascular
      complications following AF ablation over a 4 year period. METHODS: We performed
      603 catheter ablations in 539 patients from January 2004 to January 2008. All
      patients were started on coumadin immediately after procedure and received
      enoxaparin at 1 mg/kg 4 h post procedure and again 12 h later. Three protocols
      for enoxaparin, administered 12 hourly, were used post-procedure: Protocol A--1
      mg/kg x ten doses; Protocol B--1 mg/kg x six doses, and Protocol C--0.5 mg/kg x
      six doses. We documented occurrence of femoral vascular complications prior to
      discharge and at the 1 month post-op visit using a prospective database. A
      femoral vascular complication was defined as hematoma requiring prolonged
      hospitalization, blood transfusion or surgical intervention. RESULTS: There were
      21 femoral vascular complications during the study period. The rate of
      complication fell from 5.7% (protocol A) to 1.6% (protocol C) (p < 0.03). We
      attribute the decrease in complication rate to the shorter anticoagulation
      protocol, as the reduction remained significant regardless of variation in
      catheter sizes. There were no new cerebral vascular events with the lower
      enoxaparin protocols. CONCLUSION: A shorter course of post procedure
      anticoagulation protocol can reduce femoral complications without contributing to
      increased risk of thromboembolic events.

PMID- 19387808
TI  - Intracardiac echocardiography in a case with previous failed cavotricuspid
      isthmus ablation.
AB  - The Eustachian ridge (ER) can present an obstacle to cavotricuspid isthmus (CTI)
      ablation. We describe a case, where intracardiac echocardiography revealed a
      prominent ER as a likely reason for a previous failed CTI ablation and guided the
      looping of the ablation catheter around the ER, resulting in an ultimately
      successful ablation.

PMID- 19387809
TI  - Rapid ventricular pacing to optimize rotational angiography in atrial
      fibrillation ablation.
AB  - BACKGROUND: Conventional pulmonary vein (PV) angiography cannot precisely
      delineate the left atrium (LA)-PV anatomy, which is essential for the ablation of
      atrial fibrillation (AF). The aim of the study was to test the feasibility of a
      novel method of rotational angiography for the AF ablation. METHODS AND RESULTS:
      Forty-one patients were enrolled in this study. CT scanning was performed in all
      patients before the procedure. Rotational angiography (rotating from right
      anterior oblique 55 degrees to left anterior oblique 55 degrees ) was performed
      before AF ablation. Rapid ventricular pacing (RVP, 300 ms) was carried out to
      reduce cardiac output while contrast medium was injected into the LA via a
      pigtail catheter. RVP was successfully performed in 36 (87.8%) patients. The
      ostia of all PVs and the LA appendage were visible in all these 36 cases. There
      was a good correlation in the PV ostial diameters as assessed by rotational
      angiography via RVP as compared to CT imaging (r (2) > 0.85). CONCLUSIONS:
      Rotational angiography by RVP is able to delineate the LA-PV anatomy. There is a
      good correlation in the PV ostial diameters as assessed by rotational angiography
      via RVP and CT imaging. Rotational angiography by RVP is feasible during AF
      ablation.

PMID- 19387810
TI  - A streamlined technique of trans-septal endocardial left ventricular lead
      placement.
AB  - BACKGROUND: Trans-septal endocardial left ventricular (LV) lead placement has
      been used for LV pacing in a small number of patients, partially due to
      difficulty in achieving the aim in practice. METHODS: Based on analysis of the
      pre-existent techniques and exploitation of the latest developments in lead
      technologies, a new technique for trans-septal endocardial LV lead placement was
      devised. The inter-atrial septum (IAS) was punctured and a guide wire placed in
      the left atrium (LA) from the right femoral vein. A SelectSite C304-S59 catheter
      (Medtronic) was introduced from an upper body vein and deflected so that its tip
      approached the IAS puncture as marked by the guide wire already in the LA. The
      dilator supplied with the SelectSite catheter was used to engage the IAS puncture
      and pass a guide wire into the LA. The dilator was advanced over the guide wire,
      and then the catheter over the dilator, into the LA. The catheter was undeflected
      and torqued clockwise to prolapse the catheter-dilator-guide wire assembly into
      the LV cavity. The dilator-guide wire assembly was exchanged for a SelectSecure
      3830-69 cm lead, which was deployed on the LV endocardial surface. The catheter
      was withdrawn entirely into the right atrium before it was slit. RESULTS: The new
      technique was successfully implemented in a patient who required cardiac
      resynchronization therapy. CONCLUSIONS: The new technique appears more
      streamlined and efficient than the pre-existent techniques and may make trans
      septal endocardial LV lead placement a more clinically utilized alternative to
      coronary sinus and surgical epicardial LV lead placement.

PMID- 19387811
TI  - Catheter ablation of fatal ventricular tachyarrhythmias storm in acute coronary
      syndrome--role of Purkinje fiber network.
AB  - Ventricular fibrillation (VF) or ventricular tachycardia (VT) storm is a life
      threatening arrhythmia. Antiarrhythmic drugs (AADs) are not necessarily effective
      to rescue life from such conditions. Catheter ablation (CA) targeting triggering
      premature ventricular contractions (PVCs) of VF or VT that originates from
      Purkinje fiber network (PFN) is reported to be effective, especially in
      idiopathic patients. However, in condition of acute coronary syndrome (ACS), the
      efficacy of CA is not well understood. To clarify the usefulness of CA as an
      alternative way to AADs, we performed CA in four patients with VF or VT storm.
      The Purkinje potential was seen just before the myocardial ventricular wave
      during sinus rhythm that became more prominent and double components during the
      initiating PVC at the targeted area. Following CA, spontaneous episodes of VF or
      VT were no longer observed. CA is an efficacious way to bail out PFN-related VF
      or VT storm even in ACS.

PMID- 19387812
TI  - Derivation of cable parameters for a reduced model that retains asymmetric
      voltage attenuation of reconstructed spinal motor neuron dendrites.
AB  - Spinal motor neurons have voltage gated ion channels localized in their dendrites
      that generate plateau potentials. The physical separation of ion channels for
      spiking from plateau generating channels can result in nonlinear bistable firing
      patterns. The physical separation and geometry of the dendrites results in
      asymmetric coupling between dendrites and soma that has not been addressed in
      reduced models of nonlinear phenomena in motor neurons. We measured voltage
      attenuation properties of six anatomically reconstructed and type-identified cat
      spinal motor neurons to characterize asymmetric coupling between the dendrites
      and soma. We showed that the voltage attenuation at any distance from the soma
      was direction-dependent and could be described as a function of the input
      resistance at the soma. An analytical solution for the lumped cable parameters in
      a two-compartment model was derived based on this finding. This is the first two
      compartment modeling approach that directly derived lumped cable parameters from
      the geometrical and passive electrical properties of anatomically reconstructed
      neurons.

PMID- 19387813
TI  - Transgenic expression of coat protein gene of Rice tungro bacilliform virus in
      rice reduces the accumulation of viral DNA in inoculated plants.
AB  - Rice tungro, a devastating disease of rice in south and southeast Asia, is caused
      by the joint infection of Rice tungro bacilliform virus (RTBV) and Rice tungro
      spherical virus (RTSV). In order to obtain transgenic resistance against RTBV,
      indica rice cultivar Pusa Basmati-1 was transformed to express the coat protein
      (CP) gene of an Indian isolate of RTBV. Rice plants containing the transgene
      integrated in low copy numbers were obtained, in which the CP was shown to
      accumulate in the leaf tissue. The progenies representing three independent
      transformation events were challenged with Indian isolates of RTBV using
      viruliferous Green leafhoppers, and the viral titers in the inoculated plants
      were monitored using DNA dot-blot hybridization. As compared to non-transgenic
      controls, two independent transgenic lines showed significantly low levels of
      RTBV DNA, especially towards later stages of infection and a concomitant
      reduction of tungro symptoms.

PMID- 19387814
TI  - Desire for non-mutilative disability in a nonhomosexual, male-to-female
      transsexual.
AB  - In adults, the desire for a healthy limb amputation has been reported in both the
      lay press and the scientific literature. While the etiology of this condition is
      currently unknown, prevailing theories have tended to conceptualize the
      phenomenon as paraphilic in origin. In this report, we present the case of a 25
      year-old, nonhomosexual male-to-female transsexual who manifested an intense
      desire to be afflicted with a nonmutilative neurological disability (multiple
      sclerosis). The patient categorically denied sexual attraction towards the
      thought of being an amputee or physically disabled. Hypotheses are proposed for
      the development of this condition with special emphasis accorded to the
      significance of the preferred target disability.

PMID- 19387815
TI  - Biodemographic and physical correlates of sexual orientation in men.
AB  - To better understand sexual orientation from an evolutionary perspective, we
      investigated whether, compared to heterosexual men, the fewer direct descendants
      of homosexual men could be counterbalanced by a larger number of other close
      biological relatives. We also investigated the extent to which three patterns
      generally studied separately--handedness, number of biological older brothers,
      and hair-whorl rotation pattern--correlated with each other, and for evidence of
      replication of previous findings on how each pattern related to sexual
      orientation. We surveyed at Gay Pride and general community festivals, analyzing
      data for 894 heterosexual men and 694 homosexual men, both groups predominantly
      (~80%) white/non-Hispanic. The Kinsey distribution of sexual orientation for men
      recruited from the general community festivals approximated previous population
      based surveys. Compared to heterosexual men, homosexual men had both more
      relatives, especially paternal relatives, and more homosexual male relatives. We
      found that the familiality for male sexual orientation decreased with
      relatedness, i.e., when moving from first-degree to second-degree relatives. We
      also replicated the fraternal birth order effect. However, we found no
      significant correlations among handedness, hair whorl rotation pattern, and
      sexual orientation, and, contrary to some previous research, no evidence that
      male sexual orientation is transmitted predominantly through the maternal line.

PMID- 19387816
TI  - Category-specificity in sexual interest in gay men and lesbians.
AB  - The present study assessed the category-specificity of sexual interest of gay men
      and lesbians toward an understanding of the possible interaction of sex and
      sexual orientation that may exist in this phenomenon. Utilizing viewing time as a
      measure of sexual interest, we had participants (N = 99) rate the sexual appeal
      of sexually provocative pictures while the amount of time spent viewing each
      picture was inconspicuously measured. As hypothesized, same-sex oriented
      individuals demonstrated a category-specific pattern of sexual interest. That is,
      gay men and lesbians (1) viewed preferred sex pictures (i.e., of same sex)
      significantly longer than nonpreferred sex pictures (i.e., of opposite sex) and
      (2) rated preferred sex pictures as significantly more sexually appealing than
      nonpreferred sex pictures. Additionally, the difference in viewing times between
      preferred and nonpreferred sexual stimuli was not significantly different for gay
      men and lesbians, suggesting that lesbians are as category-specific as gay men.
      The implications of these findings are discussed.

PMID- 19387817
TI  - An evaluation of the validity of thermography as a physiological measure of
      sexual arousal in a non-university adult sample.
AB  - Thermography is a promising technology for the physiological measurement of
      sexual arousal in both men and women. This study was designed to extend our
      previous college student thermography study findings to an older sample (M age =
      37.05 years), add an anxiety control group to further examine the specificity of
      temperature change, and examine the relationship between genital temperature and
      a continuous measure of subjective sexual arousal. Healthy men (n = 40) and women
      (n = 39) viewed a neutral film clip after which they were randomly assigned to
      view one of four other videos: neutral (n = 20), humor (n = 19), anxiety
      provoking (n = 20) or sexually explicit (n = 20). Genital and thigh temperature
      were continuously recorded using a TSA ImagIR thermographic camera. Continuous
      and discrete reports of subjective sexual arousal were also obtained. Results
      supported the validity of thermography as a measure of sexual arousal:
      temperature change was specific to the genitals during the sexual arousal
      condition and was significantly correlated with subjective continuous and
      discrete reports of sexual arousal. Further development should assess the
      potential of thermography as a tool for the diagnosis and treatment evaluation of
      sexual arousal difficulties and for studying sex differences.

PMID- 19387818
TI  - Peripersonal space and body schema: two labels for the same concept?
AB  - To sensibly interact with the environment, like when grasping objects and
      navigating through space, the brain needs to compute not only target- and
      environment-related inputs, but also the size and spatial location of the entire
      body as well as of its parts. The neuronal construction and dynamic updating
      throughout the entire life of this bodily representation, commonly termed body
      schema in the literature, appears essential for efficient motor control and
      skillful tool-use. Meanwhile, recent contributions to the study of spatial
      multisensory processing have identified the peripersonal space as a particular
      region surrounding the body that acts as an interface between the body and the
      environment, for defensive and/or purposeful actions toward objects. In addition,
      the peripersonal space features plastic properties following tool-use that
      largely overlap those originally ascribed to the body schema, and have been
      actually interpreted as reflecting changes in the body schema itself. Here we
      seek to provide operational definitions and neuronal bases for each of these
      concepts, questioning whether sufficient evidence exists for them to be
      considered as the two faces of the same coin.

PMID- 19387819
TI  - The WHOMEN's scale (Women's HAART Optimism Monitoring and EvaluatioN Scale v.1)
      and the association with fertility intentions and sexual behaviours among HIV
      positive women in Uganda.
AB  - The objective of this study was to develop a reliable HAART optimism scale among
      HIV-positive women in Uganda and to test the scale's validity against measures of
      fertility intentions, sexual activity, and unprotected sexual intercourse. We
      used cross-sectional survey data of 540 women (18-50 years) attending Mbarara
      University's HIV clinic in Uganda. Women were asked how much they agreed or
      disagreed with 23 statements about HAART. Data were subjected to a principal
      components and factor analyses. Subsequently, we tested the association between
      the scale and fertility intentions and sexual behaviour using Wilcoxon rank sum
      test. Factor analysis yielded three factors, one of which was an eight-item HAART
      optimism scale with moderately high internal consistency (alpha = 0.70). Women
      who reported that they intended to have (more) children had significantly higher
      HAART optimism scores (median = 13.5 [IQR: 12-16]) than women who did not intend
      to have (more) children (median = 10.5 [IQR: 8-12]; P < 0.0001). Similarly, women
      who were sexually active and who reported practicing unprotected sexual
      intercourse had significantly higher HAART optimism scores than women who were
      sexually abstinent or who practiced protected sexual intercourse. Our reliable
      and valid scale, termed the Women's HAART Optimism Monitoring and EvaluatioN
      scale (WHOMEN's scale), may be valuable to broader studies investigating the role
      of HAART optimism on reproductive intentions and sexual behaviours of HIV
      positive women in high HIV prevalence settings.

PMID- 19387821
TI  - Introduction to multi-level community based culturally situated interventions.
AB  - This introduction to a special issue of the American Journal of Community
      Psychiatry is the result of a symposium at the Annual Meeting of the Society for
      Applied Anthropology, 2006, that brought together anthropologists and
      psychologists involved in community based collaborative intervention studies to
      examine critically the assumptions, processes and results of their multilevel
      interventions in local communities with local partners. The papers were an effort
      to examine context by offering a theoretical framework for the concept of "level"
      in intervention science, and advocating for "multi-level" approaches to
      social/behavioral change. They presented examples of ways in which interventions
      targeted social "levels" either simultaneously or sequentially by working
      together with communities across levels, and drawing on and co-constructing
      elements of local culture as components of the intervention. The papers raised a
      number of important issues, for example: (1) How are levels defined and how
      should collaborators be chosen; (2) does it matter at which level multilevel
      interventions begin; (3) do multilevel interventions have a greater effect on
      desired outcomes than level-specific interventions; (4) are multilevel
      interventions more sustainable; (5) are multilevel interventions cost effective
      to run, and evaluate; (6) how can theories of intervention be generated and
      adapted to each level of a multilevel intervention; (7) how should intervention
      activities at each level coordinate to facilitate community resident or target
      population empowerment? Many of these questions were only partially addressed in
      the papers presented at that time, and are more fully addressed in the
      theoretical papers, case studies and approach to evaluation included in this
      collection.

PMID- 19387820
TI  - Genetic polymorphisms of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes in
      adolescent girls with polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS), whose genetic basis is not
      completely well understood, is the most common endocrine disorder in women and it
      typically develops during adolescence. The aim of this study is to investigate
      the possible association between single nucleotide polymorphisms (SNPs) of FSHR,
      CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes and PCOS in adolescent girls.
      METHODS: DNA samples from forty-four adolescent girls with PCOS and 50 healthy
      controls were analyzed by PCR-RFLP and direct DNA sequencing to determine the
      genotypic frequency of 17 different polymorphic loci on the FSHR (A307T, N680S),
      CYP17 (-34 T/C), CYP1A1 (T6235C), CAPN10 (44, 43, 19, 63), INSR (exon 17 C/T),
      SERPINE1 (4G/5G) genes. Genotyping of exon 12 (six polymorphisms) and intron 12
      (one polymorphism) of INSR gene by direct DNA sequencing was performed for the
      first time in this study. RESULTS: No significant differences were observed in
      the genotype and allele distributions of above mentioned polymorphisms between
      cases and control groups. CONCLUSION: Our data does not support an association
      between SNPs of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes and
      susceptibility to PCOS or related traits in Turkish adolescent girls.

PMID- 19387822
TI  - Multi-level intervention to prevent influenza infections in older low income and
      minority adults.
AB  - In this paper we describe a successful multi-level participatory intervention
      grounded in principles of individual and group empowerment, and guided by social
      construction theory. The intervention addressed known and persistent inequities
      in influenza vaccination among African American and Latino older adults, and
      associated infections, hospitalizations and mortality. It was designed to
      increase resident ability to make informed decisions about vaccination, and to
      build internal and external infrastructure to support sustainability over time.
      The intervention brought a group of social scientists, vaccine researchers,
      geriatricians, public health nurses, elder services providers and advocates
      together with senior housing management and activist African American and Latino
      residents living in public senior housing in a small east coast city. Two
      buildings of equal size and similar ethnic composition were randomized as
      intervention and control buildings. Pre and post intervention surveys were
      conducted in both buildings, measuring knowledge, attitudes and peer norms.
      Processes and outcomes were documented at four levels: Influenza Strategic
      Alliance (macro and exo levels), building management (meso level), building
      resident committee (meso level) and individual residents. The Influenza Strategic
      Alliance (I.S.A.) provided ongoing resources, information and vaccine; the
      building management provided economic and other in-kind resources and supported
      residents to continue flu clinics in the building. The V.I.P. Resident Committee
      conducted flu campaigns with flu clinics in English and Spanish. The vaccination
      rate in the intervention building at post test exceeded the study goal of 70% and
      showed a significant improvement over the control building. The intervention
      achieved desired outcomes at all four levels and resulted in a significant
      increase in influenza vaccination, and improvements in pro-vaccination knowledge,
      beliefs, and understanding of health consequences.

PMID- 19387823
TI  - Youth Action Research for Prevention: a multi-level intervention designed to
      increase efficacy and empowerment among urban youth.
AB  - Youth Action Research for Prevention (YARP), a federally funded research and
      demonstration intervention, utilizes youth empowerment as the cornerstone of a
      multi-level intervention designed to reduce and/or delay onset of drug and sex
      risk, while increasing individual and collective efficacy and educational
      expectations. The intervention, located in Hartford Connecticut, served 114
      African-Caribbean and Latino high school youth in a community education setting
      and a matched comparison group of 202 youth from 2001 to 2004. The strategy used
      in YARP begins with individuals, forges group identity and cohesion, trains youth
      as a group to use research to understand their community better (formative
      community ethnography), and then engages them in using the research for social
      action at multiple levels in community settings (policy, school-based, parental
      etc.) Engagement in community activism has, in turn, an effect on individual and
      collective efficacy and individual behavioral change. This approach is unique
      insofar as it differs from multilevel interventions that create approaches to
      attack multiple levels simultaneously. We describe the YARP intervention and
      employ qualitative and quantitative data from the quasi-experimental evaluation
      study design to assess the way in which the YARP approach empowered individual
      youth and groups of youth (youth networks) to engage in social action in their
      schools, communities and at the policy level, which in turn affected their
      attitudes and behaviors.

PMID- 19387824
TI  - Community, culture and sustainability in multilevel dynamic systems intervention
      science.
AB  - This paper addresses intertwined issues in the conceptualization, implementation
      and evaluation of multilevel dynamic systems intervention science (MDSIS).
      Interventions are systematically planned, conducted and evaluated social science
      based cultural products intercepting the lives of people and institutions in the
      context of multiple additional events and processes (which also may be referred
      to as interventions) that may speed, slow or reduce change towards a desired
      outcome. Multilevel interventions address change efforts at multiple social
      levels in the hope that effects at each level will forge synergistic links,
      facilitating movement toward desired change. This paper utilizes an ecological
      framework that identifies macro (policy and regulatory institutions), meso
      (organizations and agencies with resources, and power) and micro (individuals,
      families and friends living in communities) interacting directly and indirectly.
      An MDSIS approach hypothesizes that change toward a goal will occur faster and
      more effectively when synchronized and supported across levels in a social
      system. MDSIS approaches by definition involve "whole" communities and cannot be
      implemented without the establishments of working community partnerships This
      paper takes a dynamic systems approach to science as conducted in communities,
      and discusses four concepts that are central to MDSIS--science, community,
      culture, and sustainability. These concepts are important in community based
      participatory research and to the targeting, refinement, and adaptation of
      enduring interventions. Consistency in their meaning and use can promote forward
      movement in the field of MDSIS, and in community-based prevention science.

PMID- 19387825
TI  - Effects of wellness programs in family medicine.
AB  - The objective of this research was to determine the effects of wellness programs
      on quality of life and utilization in an academic family medicine practice in two
      small controlled studies. One offered stress management and problem solving; the
      second offered a broader wellness intervention. Outcome measures consisted of
      scores on the Beck Anxiety Inventory, Hamilton Depression Inventory, CES-D
      (depression), Health Related Quality of Life, SF-12, and the number of office
      visits in 6 months. Subjects were randomly assigned to intervention or control
      groups. Statistical analysis compared pre-test and post-test values of the
      dependent variables between groups. In study one, where the focus was on
      relaxation, significant differences between groups were observed in anxiety at
      post-test (p < .03); the intervention group had lower anxiety levels. In study
      two which had a more general focus, significant group differences were found in
      days of poor mental health and number of days of depressed mood; the intervention
      group had fewer days of poor mental health (p < .05) and depression (p < .05) at
      post-test. No differences were found in utilization in either study. Based on the
      results of this research, short term wellness programs can be implemented in
      family practice and are effective in improving quality of life, but not in
      deceasing utilization in family practice patients. Matching the design of the
      program to specific patient needs may increase retention and effectiveness.

PMID- 19387826
TI  - Effects of short-term nocturnal cortisol replacement on cognitive function and
      quality of life in patients with primary or secondary adrenal insufficiency: a
      pilot study.
AB  - Cortisol replacement in patients with adrenal insufficiency usually consists of
      hydrocortisone (HC) given orally during day time. Due to the short half-life of
      hydrocortisone, cortisol levels between midnight and early morning are very low
      in contrast to the physiological rise of cortisol serum levels during this time.
      We investigated whether short-term cortisol replacement during the night improves
      cognitive function and well-being in these patients. Fourteen patients with
      adrenal insufficiency were put on HC infusion between midnight and 8 a.m. They
      subsequently underwent neurocognitive testing to measure intellectual
      functioning, concentration, memory and fine motor skills. Quality of life and
      mood were also evaluated. All tests were repeated after 2-4 weeks during usual
      oral glucocorticoid replacement therapy. Blood samples were taken for cortisol,
      epinephrine and norepinephrine measurement. With the exception of the digit
      symbol test with better scoring in the oral group (p = 0.005) there were no
      significant differences in neurocognitive testing, vegetative functions and
      quality of life on the two occasions. However, a higher cortisol level was
      associated with a worse performance in short-term memory. Plasma epinephrine
      concentration was subnormal in both groups, but increased only after intravenous
      hydrocortisone replacement. Mimicking the physiological rise in cortisol
      secretion during the night in this pilot study did neither significantly affect
      quality of life nor cognitive performance and vegetative functions. There was no
      improvement in general well being. Hydrocortisone infusion during night time
      might improve adrenomedullary reserve in patients with adrenal insufficiency.

PMID- 19387827
TI  - Never use anthracyclines with trastuzumab: it is time to reconsider the taboo.

PMID- 19387828
TI  - Norwalk virus-like particles bind specifically to A, H and difucosylated Lewis
      but not to B histo-blood group active glycosphingolipids.
AB  - Noroviruses and norovirus virus-like particles (VLPs) exhibit strain specific
      patterns in their binding to ABH and Lewis histo-blood group antigens. In this
      study we demonstrate for the first time specific binding of Norwalk virus VLPs to
      type 1 and type 2 chain glycosphingolipids (GSLs) carrying ABH and Lewis
      antigens. N-succinimidyl-3-tributylstannyl benzoate (ATE) was precursor labeled
      with (125)I and then conjugated to VLPs. The (125)I-VLPs were used in GSL thin
      layer chromatogram binding assays and displayed binding to H type 1, Lewis b, A
      type 1, A Lewis b GSLs but no binding to B type 1 or B Lewis b GSLs. For the type
      2 chain GSLs the Norwalk VLPs bound to H type 2, Lewis y, A type 2 and A Lewis y.
      In addition, the VLPs bound to several complex GSLs from blood group O and A, but
      not from blood group B red blood cells.

PMID- 19387829
TI  - Acupuncture at both ST25 and ST37 improves the pain threshold of chronic visceral
      hypersensitivity rats.
AB  - Previous studies demonstrated the efficacy of electro-acupuncture (EA) in
      relieving chronic visceral hypersensitivity (CVH) in IBS rats. However, ST25
      which is a key acupoint for patients with IBS has not been reported in these
      experiments. Eight CVH rats were treated by EA at both ST25 and ST37 for 20 min,
      once daily for seven consecutive days, model rats (n = 8) and normal rats (n = 8)
      as controls. After the first EA treatment, the abdominal withdrawal reflex scores
      were investigated to evaluate the pain threshold. After seven EA treatments, the
      concentrations of 5-hydroxytryptamine (5-HT), 5-HT3 receptor (5-HT3R) and 5-HT4
      receptor (5-HT4R) in colon tissue were assayed quantitatively by enzyme-linked
      immunosorbent assay. The results showed that EA improved the pain threshold of
      CVH rats, reduced the 5-HT concentration and increased the 5-HT4R concentration,
      but had no effect on the 5-HT3R concentration. Further studies are needed to
      optimize the choice of two-matching points for EA in the treatment of CVH rats.

PMID- 19387830
TI  - The flavonoid glycosides, myricitrin, gossypin and naringin exert anxiolytic
      action in mice.
AB  - The consumption of flavonoid-rich foods, in particular fruits and vegetables, has
      been epidemiologically associated with a reduced risk of heart disease,
      neurodegenerative disease, cancer and other chronic diseases. Flavonoid
      glycosides, the main class of flavonoids, have been shown to exert CNS-mediated
      activities, particularly as sedative-hypnotics, analgesics or both, nevertheless
      no studies have evaluated these agents in anxiety. This study assessed the
      potential anxiolytic effect of three flavonoid glycosides, myrcitrin, naringin
      and gossypin, in the elevated plus maze test (EPM). Myricitrin (1 mg/kg) was
      effective on the EPM showing a clear anxiolytic effect with no signs of sedation.
      However, higher doses showed possible sedative and myorelaxation effects.
      Gossypin and naringin both shared a similar profile, with low doses (1 mg/kg)
      inducing a robust anxiolytic effect which diminished with increasing doses of the
      flavonoids. Higher doses of these two flavonoids showed a dramatic increase in
      the open arm exploration accompanied by a decrease in locomotor activity. Hence,
      naringin (30 mg/kg) and gossypin (30 mg/kg) induce both anxiolytic and sedative
      effects. These results suggest that flavonoid glycosides have the potential to
      exert a range of CNS-mediated biological activities.

PMID- 19387832
TI  - Effects of antidepressant treatment on antiretroviral regimen adherence among
      depressed HIV-infected patients.
AB  - This study examined whether the relationship between HAART medication adherence
      and antidepressant treatment varied with HAART regimen complexity. The analysis
      included 1,192 respondents to the HIV Cost and Service Utilization Study (HCSUS)
      who were taking HAART. Self-reported past-week HAART adherence, antidepressant
      use, current mental health status, and an aggregate measure of regimen complexity
      were used in the analysis. Regression models with interactions between
      antidepressant treatment of mental health problems, poor emotional well-being or
      depressive symptoms, and medication complexity were estimated to assess
      differential associations with adherence. Irrespective of antidepressant
      treatment, poor mental health status was negatively associated with HAART
      medication adherence. However, only untreated higher depressive symptoms were
      strongly associated with maladherence to HAART medication (OR = 0.72 at P <
      0.05). Medication complexity was strongly associated with maladherence to HAART
      medication (OR = 0.96 with P < 0.05) in the model including emotional well-being;
      and weakly associated with maladherence (OR = 0.97 and P < 0.07) in the model
      including depressive and/or anxiety symptoms. However, as HAART medication
      complexity increased, adherence was higher among individuals with poorer mental
      health but using antidepressants compared to those with better mental health (OR
      = 1.09 with P < 0.05 in the model including emotional well-being; OR = 1.09 and P
      < 0.05 in the model including depressive and/or anxiety symptoms), and compared
      to those with poorer mental health but not using antidepressants (OR = 1.09, P =
      0.08 in the model including emotional well-being, and OR = 1.12, P < 0.05 in
      model including depressive and/or anxiety symptoms). In conclusion, while
      individuals with poorer mental health generally have poor HAART adherence, their
      adherence improved with the use of antidepressants as the HAART complexity
      increased.

PMID- 19387831
TI  - Guanidino acids act as rho1 GABA(C) receptor antagonists.
AB  - GABA(C) receptors play a role in myopia, memory-related disorders and circadian
      rhythms signifying a need to develop potent and selective agents for this class
      of receptors. Guanidino analogs related to glycine, beta-alanine and taurine were
      evaluated at human rho(1)GABA(C) receptors expressed in Xenopus oocytes using 2
      electrode voltage clamp methods. Of the 12 analogs tested, 8 analogs were active
      as antagonists and the remaining were inactive. (S)-2-guanidinopropionic acid
      (IC(50) = 2.2 microM) and guanidinoacetic acid (IC(50) = 5.4 microM; K (B) = 7.75
      microM [pK (B) = 5.11 +/- 0.06]) were the most potent being competitive
      antagonists at this receptor. In contrast, the beta-alanine and GABA guanidino
      analogs showed reduced activity, indicating the distance between the carboxyl
      carbon and terminal nitrogen of the guanidino group is critical for activity.
      Substituting the C2-position of guanidinoacetic acid with various alkyl groups
      reduced activity indicating that steric effects may impact on activity. The
      results of this study contribute to the structure-activity-relationship profile
      required in developing novel therapeutic agents.

PMID- 19387834
TI  - The retrospective analysis of bibliographical trends for nine biomedical
      engineering journals from 1999 to 2007.
AB  - For academic research outcomes, there is an increasing emphasis on the
      bibliometric scorings like the journal impact factor (JIF) when assessment of the
      quality of research is required. Currently, no known study has been conducted to
      explore the bibliographical trends of the biomedical engineering journals indexed
      by the annual Journal Citation Reports of the Thomson Scientific. In this study,
      the trends of nine reputable journals were selected and analyzed over a 9-year
      period (year 1999 to year 2007). The results show that the JIF rose exponentially
      for some journals (up to 597.0%) while for others, it shrank (down to -19.5%). A
      similar trend is observed for the citations trend over the same period and there
      was a significant increase in the number of citable articles published (> or
      =23.6%) in all the selected journals using year 1999 as the base year. However,
      journals which published significant more non-research articles (> or =10%) saw
      favorable subsequent effects on their citations. It is postulated that the
      changes in bibliographical trends can be classified as editorial and non
      editorial influences. The retrospective impacts of these influences on the nine
      selected journals over the 9-year period were also discussed in this study.

PMID- 19387833
TI  - Selective targeting of nanocarriers to neutrophils and monocytes.
AB  - We previously identified and characterized cell-type selective binding peptides
      from random peptide phage display libraries. Here, we used one of these peptides
      (GGP) to target liposomal nanocarriers to leukocyte subsets. To profile the
      binding selectivity of GGP-coated liposomes to human blood cells, we performed
      flow cytometric analysis with whole anti-coagulated blood. It is shown that when
      liposomal nanocarriers present these peptides on their surface, they facilitated
      cell-type specific targeting of liposomes to neutrophils and monocytes in
      contrast to nontargeted liposomes. Our data suggest that engineering the
      appropriate number of targeting peptide ligands on the nanocarrier surface is a
      factor in cell-binding selectivity, as is dose. Increasing the peptide density on
      the surface of the liposomes from 250 to 500 molecules resulted in more binding
      to neutrophils and monocytes. Fluorescence confocal microscopy corroborated the
      flow cytometry data revealing that liposomes coated with targeting GGP peptides
      decorated the surface of targeting cells and facilitate cell uptake of payload as
      evidenced by nuclear localization of tracer. These data suggest that small
      peptides identified by phage display techniques can be used to target
      nanocarriers that potentially carry therapeutic or imaging agents to leukocyte
      subsets. This ability has important implications for diseases where neutrophils
      and monocytes play a major role such as arthritis, inflammatory bowel disease,
      chronic obstructive pulmonary disease, and glomerulonephritis.

PMID- 19387835
TI  - Acculturation and violence in minority adolescents: a review of the empirical
      literature.
AB  - Although seminal reviews have been published on acculturation and mental health
      in adults and adolescents, far less is known about how acculturation influences
      adolescent interpersonal and self-directed violence. This article aims to fill
      this gap by providing a comprehensive review of research linking acculturation
      and violence behavior for adolescents of three minority populations: Latino,
      Asian/Pacific Islander (A/PI), and American Indian/Alaskan Native (AI/AN). The
      preponderance of evidence from studies on Latino and A/PI youth indicate that
      higher levels of adolescent assimilation (i.e., measured by time in the United
      States, English language use, U.S. cultural involvement, or individualism scales)
      were a risk factor for youth violence. Ethnic group identity or culture-of-origin
      involvement appear to be cultural assets against youth violence with supporting
      evidence from studies on A/PI youth; however, more studies are needed on Latino
      and AI/AN youth. Although some evidence shows low acculturation or cultural
      marginality to be a risk factor for higher levels of fear, victimization, and
      being bullied, low acculturation also serves as a protective factor against
      dating violence victimization for Latino youth. An important emerging trend in
      both the Latino and, to a lesser extent, A/PI youth literature shows that the
      impact of acculturation processes on youth aggression and violence can be
      mediated by family dynamics. The literature on acculturation and self-directed
      violence is extremely limited and has conflicting results across the examined
      groups, with high acculturation being a risk factor for Latinos, low
      acculturation being a risk factor of A/PI youth, and acculturation-related
      variables being unrelated to suicidal behavior among AI/AN youth. Bicultural
      skills training as a youth violence and suicide prevention practice is discussed.

PMID- 19387836
TI  - Interdigitated microelectrode array-coupled bipolar semiconductor photodiode
      array (IMEA-PDA) microchip for on-chip electrochemiluminescence detection.
AB  - This paper reports the design, fabrication and testing of a microchip wherein
      interdigitated microelectrode arrays (IMEA) were integrated with bipolar
      semiconductor photodiode array (PDA) chip to fabricate a highly compact
      embodiment for on-chip handling of solutions and electrochemiluminescence (ECL)
      detection. A 12 x 12 micro array of photodiodes, each coupled with an
      interdigitated microelectrode array (IMEA), an array of current amplifiers, and a
      photodiode element-addressing circuit were integrated into a single 2 x 2 cm2 IC
      chip. Each photodiode had dimensions of 300 x 300 MUm2 and the photodiode-to
      photodiode distance was 100 MUm. The chip was successfully applied to the on-chip
      quantification of electro-chemiluminescing probe-labeled single stranded
      oligonucleotides. The minimum detectable limit at signal/noise >= 3 was found to
      be 5 x 10-14 moles of oligonucleotides with a sample volume as low as 5 microl
      (i.e., 10 fmole/MUl). The attractive features of the developed IMEA-PDA microchip
      are that a plurality of samples can be analyzed simultaneously using a chip and
      that for a given sample the data can be averaged from values obtained from
      multiple, individually addressed pixels. These in turn bring in speed and
      statistical confidence in analysis. The IMEA-PDA microchip system has the
      potential to be used as a versatile and highly compact chemical analysis tool for
      chemical sensing and metrology applications.

PMID- 19387837
TI  - Microdevice for the isolation and enumeration of cancer cells from blood.
AB  - Cancer metastasis is the main attribute to cancer-related deaths. Furthermore,
      clinical reports have shown a strong correlation between the disease development
      and number of circulating tumor cells (CTCs) in the peripheral blood of cancer
      patients. Here, we present a label-free microdevice capable of isolating cancer
      cells from whole blood via their distinctively different physical properties such
      as deformability and size. The isolation efficiency is at least 80% for tests
      performed on breast and colon cancer cells. Viable isolated cells are also
      obtained which may give further insights to the understanding of the metastatic
      process. Contrasting with conventional biochemical techniques, the uniqueness of
      this microdevice lies in the mechanistic and efficient means of isolating viable
      cancer cells in blood. The microdevice has the potential to be used for routine
      monitoring of cancer development and cancer therapy in a clinical setting.

PMID- 19387838
TI  - Viagra selfhood: pharmaceutical advertising and the visual formation of Swedish
      masculinity.
AB  - Using material from the Pfizer sponsored website providing health information on
      erectile dysfunction to potential Swedish Viagra customers (www.potenslinjen.se),
      this article explores the public image of masculinity in relation to sexual
      health and the cultural techniques for creating pharmaceutical appeal. We zoom in
      on the targeted ideal users of Viagra, and the nationalized, racialized and
      sexualized identities they are assigned. As part of Pfizer's marketing strategy
      of adjustments to fit the local consumer base, the ways in which Viagra is
      promoted for the Swedish setting is telling of what concepts of masculinity are
      so stable and unassailable that they can withstand the association with a drug
      that is, in essence, an acknowledgement of 'failed' masculinity and
      'dysfunctional' sexuality. With comparative national examples, this study
      presents an interdisciplinary take on the 'glocalized' cultural imaginary of
      Viagra, and the masculine subject positions it engenders.

PMID- 19387839
TI  - The diagnostic value of fused positron emission tomography/computed tomography in
      the localization of adrenocorticotropin-secreting pituitary adenoma in Cushing's
      disease.
AB  - Despite the high resolution of magnetic resonance imaging (MRI) of the pituitary
      gland, up to 40% of cases of Cushing's disease (CD) have normal MRI. Fused images
      of positron emission tomography and computed tomography (PET-CT) may have a
      potential diagnostic role in CD in general and in such cases in particular.
      Objective of this study is to explore the diagnostic potential of PET-CT for
      localization of adrenocorticotropin-secreting pituitary adenomas in CD. PET-CT
      was performed in 12 cases with de novo (7 cases) or persistent CD (5 cases) that
      were proven to have CD on biochemical, radiological and/or histopathological
      findings. These cases had a definite CD confirmed on histopathological and
      immunostaining examination of the subsequent transphenoidal surgical specimens
      (10 cases) and/or bilateral inferior petrosal sinus sampling (IPSS, 4 cases). PET
      CT was positive in 7 of the 12 cases of CD (58%) showing a focal area of uptake
      in the pituitary gland. In these seven cases, MRI was positive in six (85.7%) but
      negative in one case (14.3%). In the other five cases with negative PET-CT, MRI
      was positive in two and negative in three cases. Of four cases with negative MRI,
      PET-CT was positive in one case (25%). We conclude that PET-CT is positive in
      around 60% of the cases of CD. Although the majority of cases with positive PET
      CT had positive MRI, PET-CT may detect some cases with negative MRI and thus
      provides important diagnostic information. If these findings are confirmed in
      larger studies, PET-CT might become an important diagnostic technique, especially
      when the more invasive and technically demanding procedure of IPSS is not
      available or inconclusive.

PMID- 19387840
TI  - The health and policy implications of job losses.

PMID- 19387841
TI  - Worldwide impact of the human papillomavirus vaccine.
AB  - OPINION STATEMENT: Nearly 500,000 new cases of cervical cancer and 274,000
      cervical cancer deaths are occurring worldwide each year. Approximately 80% of
      the 500,000 new cases occur in developing countries and this percentage is
      expected to increase to 90% by 2020. In developing countries, cervical cancer
      tends to affect relatively young poor women and is the single largest cause of
      years of life lost to cancer, since screening and treatment programs, and health
      care, in general, are relatively inaccessible to these women. Each 5-year delay
      in vaccinating women against HPV may lead to the deaths of 1.5 to 2 million women
      from cervical cancer in developing countries. The high efficacy of the two
      available cervical cancer vaccines and their proven ability to reduce the
      incidence of cervical cancer precursor lesions offer hope that the vaccine will
      have enormous worldwide impact and may dramatically reduce the cervical cancer
      burden. The current vaccines protecting against HPV-16 and HPV-18 may prevent up
      to 70% of new cervical cancers. Vaccine cross-reactivity for HPV-31, -33, -45,
      and -52 suggest that an even higher percentage of cervical cancers might be
      prevented with its use. Currently, the prohibitive cost of the vaccine precludes
      its widespread implementation. Cooperation between governments, international
      health organizations, and the vaccine industry is needed to overcome this
      significant barrier so that women are no longer denied a potentially life-saving
      advance. Worldwide HPV vaccination and cervical cancer screening should be made
      an international priority.

PMID- 19387843
TI  - Disintegration of highly soluble immediate release tablets: a surrogate for
      dissolution.
AB  - The purpose of the work was to investigate correlation between disintegration and
      dissolution for immediate release tablets containing a high solubility drug and
      to identify formulations where disintegration test, instead of the dissolution
      test, may be used as the acceptance criteria based on International Conference on
      Harmonization Q6A guidelines. A statistical design of experiments was used to
      study the effect of filler, binder, disintegrating agent, and tablet hardness on
      the disintegration and dissolution of verapamil hydrochloride tablets. All
      formulation variables, i.e., filler, binder, and disintegrating agent, were found
      to influence tablet dissolution and disintegration, with the filler and
      disintegrating agent exerting the most significant influence. Slower dissolution
      was observed with increasing disintegration time when either the filler or the
      disintegrating agent was kept constant. However, no direct corelationship was
      observed between the disintegration and dissolution across all formulations due
      to the interactions between different formulation components. Although all
      tablets containing sodium carboxymethyl cellulose as the disintegrating agent,
      disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia
      30 dissolution criteria for the verapamil hydrochloride tablets highlighting the
      dependence of dissolution process on the formulation components other than the
      disintegrating agent. The results identified only one formulation as suitable for
      using the disintegration test, instead of the dissolution test, as drug product
      acceptance criteria and highlight the need for systematic studies before using
      the disintegration test, instead of the dissolution test as the drug acceptance
      criteria.

PMID- 19387842
TI  - Post-operative radiation therapy (PORT) in completely resected non-small-cell
      lung cancer.
AB  - High-level evidence to guide the optimal postoperative management of patients
      with completely resected non-small-cell lung cancer (NSCLC) is lacking. Large
      randomized controlled trials have established postoperative chemotherapy as the
      standard of care for patients with pathologically involved lymph nodes. Recent
      retrospective and non-randomized studies provide evidence of the benefit of post
      operative radiation therapy (PORT) in patients with mediastinal nodal involvement
      (N2 stage). A large multi-institutional randomized trial of PORT in this patient
      population is now underway. Based on currently available data, PORT may be
      considered for fit patients with completely resected NSCLC with N2 nodal
      involvement, preferably after completion of adjuvant chemotherapy. At this point,
      PORT is not recommended for patients with less than N2 nodal stage. Ideally,
      modern three-dimensional conformal radiation technique should be used, with
      attention to normal organ sparing, particularly lung and heart. Appropriate image
      guidance tools are encouraged to individualize treatment margins, account for
      breathing-induced motion, and minimize irradiation of normal tissues. The target
      volume should include at a minimum the bronchial stump, ipsilateral hilum, and
      involved nodal stations, and covering adjacent mediastinal nodal stations is
      recommended. A total dose of 50-54 Gy in 1.8-2 Gy fractions is appropriate.

PMID- 19387844
TI  - The NMR structure of the TC10- and Cdc42-interacting domain of CIP4.

PMID- 19387845
TI  - Counting mtDNA molecules in Phaseolus vulgaris: sublimons are constantly produced
      by recombination via short repeats and undergo rigorous selection during
      substoichiometric shifting.
AB  - Sublimons are substoichiometric DNA molecules which are generated by
      recombinations across short repeats, located in main mitochondrial genome of
      plants. Since short repeats are believed to recombine irreversibly and to be
      usually inactive, it is unknown how substoichiometric sequences are maintained.
      Occasionally, sublimons are amplified during substoichiometric shifting (SSS) and
      take the role of the main genome. Using the Phaseolus vulgaris system, we have
      addressed the questions concerning accumulation of sublimons, the role of
      recombination in their maintenance and selective amplification during SSS. We
      found that sublimons accompanied by parental recombination sequences were
      maintained by constant recombination across a short 314-bp repeat. The abundance
      of these sublimons was three orders of magnitude higher than accumulation of
      those which could not be maintained by recombination because their parental forms
      were absent from the main genome. As expected for active recombination, two
      recombination-derived sublimons were equimolar and so were their parental forms.
      One parental and one substoichiometric form shared the A/C polymorphism
      indicating their frequent inter-conversion. Only the C variant of the sublimon
      was amplified during substoichiometric shift implying strong selection of DNA
      molecules operating during SSS.

PMID- 19387847
TI  - Rapid response to perturbation of chromosome frequencies in natural populations
      of Drosophila robusta.
AB  - Perturbation of gene or chromosome frequencies in natural populations is one of
      the most powerful ways of demonstrating whether natural selection maintains
      genetic polymorphism or if other evolutionary forces are at work. Gene
      arrangement frequencies in two natural populations of Drosophila robusta were
      perturbed multiple times by releasing adult flies with contrasting karyotypes and
      carefully monitoring post-perturbation presence of hybrids and chromosome
      frequencies. In all cases, frequencies quickly returned to pre-perturbation
      levels, and in the following sampling periods, no evidence of the introduced
      chromosomes was apparent. Analysis of post-perturbation frequency changes
      included tests for heterogeneity among chromosome arrangements in rates of return
      to equilibrium values using population admixture analysis. In several cases,
      significant heterogeneity was detected indicating some form of natural selection
      was operating. Technical challenges to carrying out perturbation experiments in
      the wild are also discussed.

PMID- 19387846
TI  - Next generation synthetic vectors for transformation of the plastid genome of
      higher plants.
AB  - Plastid transformation vectors are E. coli plasmids carrying a plastid marker
      gene for selection, adjacent cloning sites and flanking plastid DNA to target
      insertions in the plastid genome by homologous recombination. We report here on a
      family of next generation plastid vectors carrying synthetic DNA vector arms
      targeting insertions in the rbcL-accD intergenic region of the tobacco (Nicotiana
      tabacum) plastid genome. The pSS22 plasmid carries only synthetic vector arms
      from which the undesirable restriction sites have been removed by point
      mutations. The pSS24 vector carries a c-Myc tagged spectinomycin resistance
      (aadA) marker gene whereas in vector pSS30 aadA is flanked with loxP sequences
      for post-transformation marker excision. The synthetic vectors will enable direct
      manipulation of passenger genes in the transformation vector targeting insertions
      in the rbcL-accD intergenic region that contains many commonly used restriction
      sites.

PMID- 19387848
TI  - Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors
      to the lungs.
AB  - Tumor treating fields (TTFields) are low intensity, intermediate frequency,
      alternating electric fields used to treat cancerous tumors. This novel treatment
      modality effectively inhibits the growth of solid tumors in vivo and has shown
      promise in pilot clinical trials in patients with advanced stage solid tumors.
      TTFields were tested for their potential to inhibit metastatic spread of solid
      tumors to the lungs in two animal models: (1) Mice injected with malignant
      melanoma cells (B16F10) into the tail vein, (2) New Zealand White rabbits
      implanted with VX-2 tumors within the kidney capsule. Mice and rabbits were
      treated using two-directional TTFields at 100-200 kHz. Animals were either
      monitored for survival, or sacrificed for pathological and histological analysis
      of the lungs. The total number of lung surface metastases and the absolute weight
      of the lungs were both significantly lower in TTFields treated mice then in sham
      control mice. TTFields treated rabbits survived longer than sham control animals.
      This extension in survival was found to be due to an inhibition of metastatic
      spread, seeding or growth in the lungs of TTFields treated rabbits compared to
      controls. Histologically, extensive peri- and intra-tumoral immune cell
      infiltration was seen in TTFields treated rabbits only. These results raise the
      possibility that in addition to their proven inhibitory effect on the growth of
      solid tumors, TTFields may also have clinical benefit in the prevention of
      metastatic spread from primary tumors.

PMID- 19387849
TI  - Expression of EGR-1 in a subset of olfactory bulb dopaminergic cells.
AB  - In the adrenal medulla, binding of the immediate early gene (IEG) proteins, EGR-1
      (ZIF-268/KROX-24/NGFI-A) and AP-1, to the tyrosine hydroxylase (Th) proximal
      promoter mediate inducible Th expression. The current study investigated the
      potential role of EGR-1 in inducible Th expression in the olfactory bulb (OB)
      since IEGs bound to the AP-1 site in the Th proximal promoter are also necessary
      for activity-dependent OB TH expression. Immunohistochemical analysis of a naris
      occluded mouse model of odor deprivation revealed weak EGR-1 expression levels in
      the OB glomerular layer that were activity-dependent. Immunofluorescence analysis
      indicated that a majority of glomerular cells expressing EGR-1 also co-expressed
      TH, but only small subset of TH-expressing cells contained EGR-1. By contrast,
      granule cells, which lack TH, exhibited EGR-1 expression levels that were
      unchanged by naris closure. Together, these finding suggest that EGR-1 mediates
      activity-dependent TH expression in a subset of OB dopaminergic neurons, and that
      there is differential regulation of EGR-1 in periglomerular and granule cells.

PMID- 19387850
TI  - Is high concentration of parvalbumin a requirement for superfast relaxation?
AB  - It is generally thought that the rapid relaxation of fast muscles is facilitated
      by the Ca(2+) binding protein parvalbumin (Parv). Indeed superfast swimbladder
      (SWB) muscle of toadfish contains the largest concentration of this protein ever
      observed (up to 1.5 mM). At 15 degrees C toadfish perform a 100 Hz call, 400 ms
      in duration, followed by a long (5-15 s) intercall interval. It has been proposed
      that Parv helps sequester the Ca(2+) during the call, and then Ca(2+) unbinds and
      is pumped back into the sarcoplasmic reticulum during the long intercall
      interval. Midshipman (Porichthys notatus) is another fish which calls at a high
      frequency; 80-100 Hz at a temperature of 12-15 degrees C. However, unlike
      toadfish, midshipman call with a 100% duty cycle. Without an intercall interval,
      Parv would seem of little use as it would become saturated early in calling. Here
      we show that the midshipman SWB has only about 1/8th of the Parv in toadfish.
      Moreover, total Parv content in calling male midshipman SWB was not different
      from that in the non-calling female and the much slower locomotory muscles. These
      data suggest that Parv does not play a large role in the calling of midshipman,
      which is accomplished without a high concentration of this protein. Native gel
      electrophoresis also revealed presence of three major (PA-I, PA-II and PA-III)
      and two minor (PA-Ia and PA-IIIa, <5% of total content) Parv isoforms in adult
      toadfish SWB. Midshipman SWB contained about equal amounts of PA-I and PA-II and
      also a small (approximately 10%) amount of PA-III. By amino acid composition,
      toadfish PA-Ia and PA-I isoforms were different from PA-II and PA-III isoforms
      (by 24 and 14 residues, respectively).

PMID- 19387851
TI  - Adiposity in relation to colorectal adenomas and hyperplastic polyps in women.
AB  - OBJECTIVE: To examine whether BMI is independently related to colorectal adenomas
      and hyperplastic polyps. METHODS: We conducted a cross-sectional study among
      1,420 asymptomatic women aged 40-79 years who had undergone complete colonoscopy.
      Logistic regression was used to estimate the odds ratios (OR) and the
      corresponding 95% confidence intervals (CI) of adenomas and hyperplastic polyps.
      RESULTS: We identified 953 women (67.1%) with no polyps, 292 (20.6%) with
      adenomas, and 175 (12.3%) with hyperplastic polyps. Among those with polyps, 75
      women (5.3% of total women) were classified as having both adenomas and
      hyperplastic polyps. After adjusting for potential risk factors for colorectal
      cancer, BMI was related to increased risk of adenomas (OR comparing obese to
      normal weight women = 1.57; 95% CI = 1.07-2.29). Further, BMI was associated with
      enhanced risk of hyperplastic polyps (OR = 3.76; 95% CI = 2.35-6.01) and the
      combination of adenomas and hyperplastic polyps (OR = 2.84; 95% CI = 1.41-5.72).
      CONCLUSIONS: Excess body mass is positively related to colorectal adenomas and
      hyperplastic polyps, particularly when both kinds of polyps are present in
      combination. Future studies should continue to delineate the possible differences
      in potential risk factors between colorectal adenomas and hyperplastic polyps.
      Such work should help further elucidate the possible causes of colorectal cancer.

PMID- 19387852
TI  - Consumption of sweet foods and breast cancer risk: a case-control study of women
      on Long Island, New York.
AB  - Several epidemiologic studies have reported a positive association between breast
      cancer risk and high intake of sweets, which may be due to an insulin-related
      mechanism. We investigated this association in a population-based case-control
      study of 1,434 cases and 1,440 controls from Long Island, NY. Shortly after
      diagnosis, subjects were interviewed in-person to assess potential breast cancer
      risk factors, and self-completed a modified Block food frequency questionnaire,
      which included 11 items pertaining to consumption of sweets (sweet beverages,
      added sugars, and various desserts) in the previous year. Using unconditional
      logistic regression models, we estimated the association between consumption of
      sweets and breast cancer. Consumption of a food grouping that included dessert
      foods, sweet beverages, and added sugars was positively associated with breast
      cancer risk [adjusted odds ratio (OR) comparing the highest to the lowest
      quartile: 1.27, 95% confidence interval (CI): 1.00-1.61]. The OR was slightly
      higher when only dessert foods were considered (OR: 1.55, 95% CI: 1.23-1.96). The
      association with desserts was stronger among pre-menopausal women (OR: 2.00, 95%
      CI: 1.32-3.04) than post-menopausal women (OR: 1.40, 95% CI: 1.07-1.83), although
      the interaction with menopause was not statistically significant. Our study
      indicates that frequent consumption of sweets, particularly desserts, may be
      associated with an increased risk of breast cancer. These results are consistent
      with other studies that implicate insulin-related factors in breast
      carcinogenesis.

PMID- 19387853
TI  - Thermal terrain modeling of spatial objects, a tool for environmental and
      climatic change assessment.
AB  - The aim of the current research effort is to include biophysical multi-temporal
      data and more specifically land surface temperature (LST) in the terrain modeling
      process that traditionally was based only on digital elevation data processing.
      The terrain partition framework (spatial objects) is defined by the borderlines
      of prefecture authorities of Greece. Each object is represented by a set of
      attributes derived from the digital elevation data, and objects are organized
      into clusters on the basis of their terrain dependent representation. Finally,
      the terrain is segmented to regions on the basis of the multi-temporal LST data,
      each region presenting a different thermal signature. The thermal regions are
      used in the spatial objects parametric representation and a new index is devised
      (LST climatic index) expressing the biophysical suitability of spatial objects at
      moderate resolution scale.

PMID- 19387854
TI  - Airborne pollen in European and Asian parts of Istanbul.
AB  - Pollen concentrations in the atmosphere of Istanbul, a city located between two
      continents, has been monitored for 1 year as part of a larger research program.
      The sampling sites were located in two different continents: the Asian part (AS)
      and the European part (EP). The sampling was performed in AS and EP of the city
      by using Hirst type volumetric method, and pollen grains of 58 and 62 taxa were
      identified in the two parts, respectively. The pollen spectrum reflected the
      floristic diversity of the region. The main pollen producers at the sites were
      characterized by some allergenic pollen and were identified as
      Cupressaceae/Taxaceae, Urticaceae, Pistacia sp., Quercus sp., Platanus sp.,
      Fraxinus sp., and Xanthium sp. These pollen types contributed to the total pollen
      sum with a percentage of more than 80% at both monitoring sites. The highest
      amount of pollen grains was recorded in April. The greatest number of species was
      recorded in May, when 42 types (AS) and 44 types (EP) were present.

PMID- 19387855
TI  - Ionic and heavy metal composition of respirable particulate in Madurai, India.
AB  - Airborne particulate matter (PM(10)) was collected for a period of 1 year at six
      locations in Madurai city, India. The chemical analyses on PM(10) samples were
      carried out for the estimation of heavy metals and ions using atomic absorption
      spectroscopy and ion chromatography respectively. The average PM(10)
      concentrations varied from 97.2 to 152.5 microg/m(3), which were found to be
      below the Indian air quality standards. While industrial areas had the highest
      concentrations of heavy metals such as Fe, Zn and Cr and also the SO(4)(2-) ions,
      traffic areas with relatively higher traffic densities in the city endured
      highest concentrations of Cd and the NO(3)(-) ion. As gaseous pollutants serve as
      precursors of ionic particles in the atmospheric environment, gaseous pollution
      control is necessitated along with particulate with special reference to heavy
      metal and ion pollution abatement for the sustainable development of Madurai
      city.

PMID- 19387856
TI  - A saprobic index for biological assessment of river water quality in Brazil
      (Minas Gerais and Rio de Janeiro states).
AB  - Based upon several years of experience in investigations with macrozoobenthos in
      rivers in the states of Minas Gerais and Rio de Janeiro, a biological assessment
      system has been developed to indicate pollution levels caused by easily
      degradable organic substances from sewers. The biotic index presented here is
      aimed at determining water's saprobic levels and was, therefore, named the
      "Saprobic Index for Brazilian Rivers in Minas Gerais and Rio de Janeiro states"
      (ISMR). For this purpose, saprobic valences and weights have been established for
      122 taxa of tropical macrozoobenthos. Investigations were carried out in little,
      medium sized and big rivers in mountains and plains. Through ISMR, a
      classification of water quality and the respective cartographic representation
      can be obtained. Data collection and treatment methods, as well as the
      limitations of the biotic index, are thoroughly described. ISMR can also be used
      as an element to establish complex multimetric indexes intended for an ecological
      integrity assessment, where it is essential to indicate organic pollution.

PMID- 19387857
TI  - Investigation of immunmodulatory effects of levamisole and vitamin E on Immunity
      and some blood parameters in newborn Jersey calves.
AB  - The immunmodulatory effects of dl-alpha tocopherol (vitamin E) and levamisole on
      the immune system and some blood parameters of newborn Jersey calves were
      investigated with the present study. Treatment groups 1, 2 and 3 were injected
      13,3 ml isotonic saline solution (0,9% NaCl), 3 mg/kg levamisole HCl and 2000 IU
      vitamin E weekly, starting at birth until the age of two weeks. Average serum IgM
      levels of the control, levamisole and vitamin E calves were 111,7 +/- 9,3 mg/100
      ml, 251,9 +/- 27,6 mg/100 ml, 202,2 +/- 43,3 mg/100 ml respectively on day 22.
      Average serum IgG levels of the levamisole and vitamin E groups elevated,
      compared to the control group on days 1, 8, 15 and 22. However, there were
      stastistically differences in treatment and control groups for serum total
      cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL),
      triglyceride and cortisol values and whole blood counts. All differences were in
      the reference ranges. Levamisole and vitamin E could be used as an alternative
      way for their beneficial effects such as improving the humoral immune responses
      of calves and their safety and practical use against the neonatal period
      infections in the field.

PMID- 19387858
TI  - Modulating mouse innate immunity to RNA viruses by expressing the Bos taurus Mx
      system.
AB  - Mx proteins are interferon-induced members of the dynamin superfamily of large
      guanosine triphosphatases. These proteins have attracted much attention because
      some display antiviral activity against pathogenic RNA viruses, such as members
      of the orthomyxoviridae, bunyaviridae, and rhabdoviridae families. Among the
      diverse mammalian Mx proteins examined so far, we have recently demonstrated in
      vitro that the Bos taurus isoform 1 (boMx1) is endowed with exceptional anti
      rabies-virus activity. This finding has prompted us to seek an appropriate in
      vivo model for confirming and evaluating gene therapy strategies. Using a BAC
      transgene, we have generated transgenic mouse lines expressing the antiviral
      boMx1 protein and boMx2 proteins under the control of their natural promoter and
      short- and long-range regulatory elements. Expressed boMx1 and boMx2 are
      correctly assembled, as deduced from mRNA sequencing and western blotting. Poly
      I/C-subordinated expression of boMx1 was detected in various organs by
      immunohistochemistry, and transgenic lines were readily classified as high- or
      low-expression lines on the basis of tissue boMx1 concentrations measured by
      ELISA. Poly-I/C-induced Madin-Darby bovine kidney cells, bovine turbinate cells,
      and cultured cells from high-expression line of transgenic mice were found to
      contain about the same concentration of boMx1, suggesting that this protein is
      produced at near-physiological levels. Furthermore, insertion of the bovine Mx
      system rendered transgenic mice resistant to vesicular-stomatitis-virus
      associated morbidity and mortality, and embryonic fibroblasts derived from high
      expression transgenic mice were far less permissive to the virus. These results
      demonstrate that the Bos taurus Mx system is a powerful anti-VSV agent in vivo
      and suggest that the transgenic mouse lines generated here constitute a good
      model for studying in vivo the various antiviral functions-known and yet to be
      discovered-exerted by bovine Mx proteins, with priority emphasis on the antirabic
      function of boMx1.

PMID- 19387859
TI  - Low crop plant population densities promote pollen-mediated gene flow in spring
      wheat (Triticum aestivum L.).
AB  - Transgenic wheat is currently being field tested with the intent of eventual
      commercialization. The development of wheat genotypes with novel traits has
      raised concerns regarding the presence of volunteer wheat populations and the
      role they may play in facilitating transgene movement. Here, we report the
      results of a field experiment that investigated the potential of spring wheat
      plant population density and crop height to minimize gene flow from a herbicide
      resistant (HR) volunteer population to a non-HR crop. Pollen-mediated gene flow
      (PMGF) between the HR volunteer wheat population and four conventional spring
      wheat genotypes varying in height was assessed over a range of plant population
      densities. Natural hybridization events between the two cultivars were detected
      by phenotypically scoring plants in F(1) populations followed by verification
      with Mendelian segregation ratios in the F(1:2) families. PMGF was strongly
      associated with crop yield components, but showed no association with flowering
      synchrony. Maximum observed PMGF was always less than 0.6%, regardless of crop
      height and density. The frequency of PMGF in spring wheat decreased exponentially
      with increasing plant population density, but showed no dependence on either crop
      genotype or height. However, increasing plant densities beyond the recommended
      planting rate of 300 cropped wheat plants m(-2) provided no obvious benefit to
      reducing PMGF. Nevertheless, our results demonstrate a critical plant density of
      175-200 cropped wheat plants m(-2) below which PMGF frequencies rise
      exponentially with decreasing plant density. These results will be useful in the
      development of mechanistic models and best management practices that collectively
      facilitate the coexistence of transgenic and nontransgenic wheat crops.

PMID- 19387860
TI  - Acute kidney injury due to anabolic steroid and vitamin supplement abuse: report
      of two cases and a literature review.
AB  - BACKGROUND: The use of anabolic steroids and vitamin supplements has reached
      alarming proportions in the last decades. Adverse effects have been documented
      and include virilization, feminization, adverse lipid profile, psychiatric
      disorders, cardiac and liver disease. Acute kidney injury (AKI) is not frequently
      described. The purpose of this study is to report two cases of AKI associated
      with anabolic steroid and vitamin supplement abuse. CASE REPORT: Two men, aged 21
      and 30 years, presented to the Emergency Department with abdominal pain, nausea
      and vomiting. They reported the use of anabolic steroids and veterinary
      supplements with vitamins A, D and E. Laboratory tests showed AKI (serum urea 79
      and 52 mg/dl, serum creatinine 3.9 and 1.9 mg/dl) and hypercalcemia (calcium 13.2
      and 11 mEq/l). Kidney biopsies showed inflammatory interstitial nephritis and
      acute tubular necrosis. Treatment consisted of vigorous hydration with
      simultaneous use of furosemide and discontinuation of the vitamins and anabolic
      substances, and resulted in recovery of renal function. CONCLUSIONS: AKI is an
      important complication of anabolic steroid and vitamin supplement abuse. The
      exact pathophysiology of this type of AKI remains unclear. The main cause of
      renal dysfunction in these cases seems to be the vitamin D intoxication and drug
      induced interstitial nephritis. It is mandatory to start early treatment for
      serious hypercalcemia, with vigorous venous hydration, diuretics and
      corticosteroids.

PMID- 19387861
TI  - Visual estimation of patients' body weight in hospital: the more observers, the
      better?
AB  - OBJECTIVE: Patients are not always weighed in hospitals. A visual estimate of
      patients' body weight is often used. Little information exists about the validity
      of this practice. We assessed the visual estimation of body weight in a
      population of elderly hospitalised patients. METHOD: Three observers performed a
      visual estimation of weight in 71 geriatric patients. Estimated body weights from
      each observer were compared to measured body weights. Various panels--three
      panels of two observers and two panels of three observers--were also evaluated.
      RESULTS: Overall results showed that a three observer panel gave better weight
      estimates than one or two individuals. CONCLUSION: While further clinical studies
      are necessary to confirm these findings, using the mean or the median of several
      visual estimates may be a practical solution for body weight estimation when
      weighing patients is not possible.

PMID- 19387862
TI  - Characterisation of RC-proteoliposomes at different RC/lipid ratios.
AB  - Reconstitution of membrane proteins in phospholipid vesicles allows the
      investigation of such macromolecules in a biomimetic simplified environment. The
      often employed micelle-to-vesicle-transition method for proteoliposome
      preparation is a fast and reproducible technique. In this, communication is shown
      that the lipid/protein ratio influences the size of the proteoliposomes and the
      actual protein reconstitution. The results indicate that for photosynthetic
      reaction centres, the best conditions for ligand-interaction experiments are
      achieved with a lipid/protein value of 1000:1, while for complete protein
      incorporation, the 2000:1 ratio should be chosen.

PMID- 19387863
TI  - Survival of akinetes (resting-state cells of cyanobacteria) in low earth orbit
      and simulated extraterrestrial conditions.
AB  - Cyanobacteria are photosynthetic organisms that have been considered for space
      applications, such as oxygen production in bioregenerative life support systems,
      and can be used as a model organism for understanding microbial survival in
      space. Akinetes are resting-state cells of cyanobacteria that are produced by
      certain genera of heterocystous cyanobacteria to survive extreme environmental
      conditions. Although they are similar in nature to endospores, there have been no
      investigations into the survival of akinetes in extraterrestrial environments.
      The aim of this work was to examine the survival of akinetes from Anabaena
      cylindrica in simulated extraterrestrial conditions and in Low Earth Orbit (LEO).
      Akinetes were dried onto limestone rocks and sent into LEO for 10 days on the ESA
      Biopan VI. In ground-based experiments, the rocks were exposed to periods of
      desiccation, vacuum (0.7*10(-3) kPa), temperature extremes (-80 to 80 degrees C),
      Mars conditions (-27 degrees C, 0.8 kPa, CO(2)) and UV radiation (325-400 nm). A
      proportion of the akinete population was able to survive a period of 10 days in
      LEO and 28 days in Mars simulated conditions, when the rocks were not subjected
      to UV radiation. Furthermore, the akinetes were able to survive 28 days of
      exposure to desiccation and low temperature with high viability remaining. Yet
      long periods of vacuum and high temperature were lethal to the akinetes. This
      work shows that akinetes are extreme-tolerating states of cyanobacteria that have
      a practical use in space applications and yield new insight into the survival of
      microbial resting-state cells in space conditions.

PMID- 19387865
TI  - Enzyme analysis for Pompe disease in leukocytes; superior results with natural
      substrate compared with artificial substrates.
AB  - Enzyme analysis for Pompe disease in leukocytes has been greatly improved by the
      introduction of acarbose, a powerful inhibitor of interfering alpha-glucosidases,
      which are present in granulocytes but not in lymphocytes. Here we show that the
      application of acarbose in the enzymatic assay employing the artificial substrate
      4-methylumbelliferyl-alpha-D: -glucoside (MU-alphaGlc) is insufficient to clearly
      distinguish patients from healthy individuals in all cases. Also, the ratios of
      the activities without/with acarbose only marginally discriminated Pompe patients
      and healthy individuals. By contrast, when the natural substrate glycogen is
      used, the activity in leukocytes from patients (n = 82) with Pompe disease is at
      most 17% of the lowest control value. The use of artificial substrate in an assay
      with isolated lymphocytes instead of total leukocytes is a poor alternative as
      blood samples older than one day invariably yield lymphocyte preparations that
      are contaminated with granulocytes. To diagnose Pompe disease in leukocytes we
      recommend the use of glycogen as substrate in the presence of acarbose. This
      assay unequivocally excludes Pompe disease. To also exclude pseudo-deficiency of
      acid alpha-glucosidase caused by the sequence change c.271G>A (p.D91N or GAA2;
      homozygosity in approximately 1:1000 caucasians), a second assay employing MU
      alphaGlc substrate plus acarbose or DNA analysis is required.

PMID- 19387866
TI  - The pharmacological chaperone 1-deoxygalactonojirimycin increases alpha
      galactosidase A levels in Fabry patient cell lines.
AB  - Fabry disease is an X-linked lysosomal storage disorder caused by mutations in
      the gene encoding alpha-galactosidase A (alpha-Gal A), with consequent
      accumulation of its major glycosphingolipid substrate, globotriaosylceramide (GL
      3). Over 500 Fabry mutations have been reported; approximately 60% are missense.
      The iminosugar 1-deoxygalactonojirimycin (DGJ, migalastat hydrochloride, AT1001)
      is a pharmacological chaperone that selectively binds alpha-Gal A, increasing
      physical stability, lysosomal trafficking, and cellular activity. To identify DGJ
      responsive mutant forms of alpha-Gal A, the effect of DGJ incubation on alpha-Gal
      A levels was assessed in cultured lymphoblasts from males with Fabry disease
      representing 75 different missense mutations, one insertion, and one splice-site
      mutation. Baseline alpha-Gal A levels ranged from 0 to 52% of normal. Increases
      in alpha-Gal A levels (1.5- to 28-fold) after continuous DGJ incubation for 5
      days were seen for 49 different missense mutant forms with varying EC(50) values
      (820 nmol/L to >1 mmol/L). Amino acid substitutions in responsive forms were
      located throughout both structural domains of the enzyme. Half of the missense
      mutant forms associated with classic (early-onset) Fabry disease and a majority
      (90%) associated with later-onset Fabry disease were responsive. In cultured
      fibroblasts from males with Fabry disease, the responses to DGJ were comparable
      to those of lymphoblasts with the same mutation. Importantly, elevated GL-3
      levels in responsive Fabry fibroblasts were reduced after DGJ incubation,
      indicating that increased mutant alpha-Gal A levels can reduce accumulated
      substrate. These data indicate that DGJ merits further evaluation as a treatment
      for patients with Fabry disease with various missense mutations.

PMID- 19387867
TI  - Serum eye drops, amniotic membrane and limbal epithelial stem cells--tools in the
      treatment of ocular surface disease.
AB  - The advent of serum eye drops, amniotic membrane and limbal stem cell grafts,
      have transformed the treatment of diseases which result in ocular surface
      failure. This article provides an overview of ocular surface anatomy and failure,
      and how the use of serum eye drops, amniotic membrane and limbal epithelial stem
      cell transplantation has influenced ophthalmological practice both historically
      and in recent years. This review focuses on the rationale for the use of these
      emerging tools, how they are prepared, clinical applications, limitations, and
      speculates on future directions.

PMID- 19387868
TI  - What tissue bankers should know about the use of allograft meniscus in
      orthopaedics.
AB  - The menisci of the knee are two crescent shaped cartilage shock absorbers sitting
      between the femur and the tibia, which act as load sharers and shock absorbers.
      Loss of a meniscus leads to a significant increase in the risk of developing
      arthritis in the knee. Replacement of a missing meniscus with allograft tissue
      can reduce symptoms and may potentially reduce the risk of future arthritis.
      Meniscal allograft transplantation is a complex surgical procedure with many
      outstanding issues, including 'what techniques should be used for processing and
      storing grafts?', 'how should the allografts be sized?' and 'what surgical
      implantation techniques might be most appropriate?' Further clinical research is
      needed and close collaboration between the users (surgeons) and the suppliers
      (tissue banks) is essential. This review explores the above subject in detail.

PMID- 19387869
TI  - Myogenic tone in mouse mesenteric arteries: evidence for P2Y receptor-mediated,
      Na(+), K (+), 2Cl (-) cotransport-dependent signaling.
AB  - This study examines the action of agonists and antagonists of P2 receptors on
      mouse mesenteric artery contractions and the possible involvement of these
      signaling pathways in myogenic tone (MT) evoked by elevated intraluminal
      pressure. Both ATP and its non-hydrolyzed analog alpha,beta-ATP triggered
      transient contractions that were sharply decreased in the presence of NF023, a
      potent antagonist of P2X(1) receptors. In contrast, UTP and UDP elicited
      sustained contractions which were suppressed by MRS2567, a selective antagonist
      of P2Y(6) receptors. Inhibition of Na(+), K(+), 2Cl(-) cotransport (NKCC) with
      bumetanide led to attenuation of contractions in UTP- but not ATP-treated
      arteries. Both UTP-induced contractions and MT were suppressed by MRS2567 and
      bumetanide but were insensitive to NF023. These data implicate a P2Y(6)-mediated,
      NKCC-dependent mechanism in MT of mesenteric arteries. The action of heightened
      intraluminal pressure on UTP release from mesenteric arteries and its role in the
      triggering of P2Y(6)-mediated signaling should be examined further.

PMID- 19387870
TI  - Mass spectrometry identifies LGI1-interacting proteins that are involved in
      synaptic vesicle function in the human brain.
AB  - The LGI1 gene has been shown to predispose to epilepsy and influence cell
      invasion in glioma cells. To identify proteins that interact with LGI1 and gain a
      better understanding of its function, we have used co-immunoprecipitation (co-IP)
      of a secreted green fluorescent protein-tagged LGI1 protein combined with mass
      spectrometry to identify interacting partners from lysates prepared from human
      subcortical white matter. Proteins were recovered from polyacrylamide gels and
      analyzed using liquid chromatography coupled to tandem mass spectrometry. This
      analysis identified a range of proteins, but in particular synaptotagmin,
      synaptophysin, and syntaxin 1A. Each of these proteins is found associated with
      synaptic vesicles. These interactions were confirmed independently by co-IP and
      Western blotting and implicate LGI1 in synapse biology in neurons. Other vesicle
      related proteins that were recovered by co-IP include clathrin heavy chain 1,
      syntaxin binding protein 1, and a disintegrin and metalloprotease 23. These
      observations support a role for LGI1 in synapse vesicle function in neurons.

PMID- 19387871
TI  - Role of vasopressor administration in patients with acute neurologic injury.
AB  - INTRODUCTION: Pharmacologic blood pressure elevation is often utilized to prevent
      or treat ischemia in patients with acute neurologic injury, and routinely
      requires administration of vasopressor agents. Depending on the indication,
      vasopressor agents may be administered to treat hypotension or to induce
      hypertension. METHODS: Although numerous guideline statements exist regarding the
      management of blood pressure in these patients, most recommendations are based
      largely on Class III evidence. Further, there are few randomized controlled
      trials comparing vasopressor agents in these patients and selection is often
      guided by expert consensus. RESULTS: We discuss the clinical evidence regarding
      vasopressor administration for blood pressure management in patients with acute
      neurologic injury. The effect of various vasopressors on cerebral hemodynamics is
      also discussed. CONCLUSION: Although high-quality clinical data are scarce, the
      available evidence suggests that norepinephrine should be considered as the
      vasopressor of choice when blood pressure elevation is indicated in patients with
      acute neurologic injury.

PMID- 19387872
TI  - FSHbeta knockout mouse model: a decade ago and into the future.
AB  - In 1997, more than 10 years ago now, we first reported the phenotypes of follicle
      stimulating hormone (FSH) beta null mice. Since then, these mice have been useful
      for various physiological and genetic studies in reproductive biology. More
      recently, extra-gonadal functions of FSH have been discovered in bone. These
      studies opened up exciting avenues of new research on osteoporosis in
      postmenopausal women. Several genomics and proteomics tools and novel strategies
      to spatio-temporally restricting gene expression in vivo are available now. It is
      hoped that with the aid of these and other emerging technologies, an integrated
      network of FSH signaling pathways in various tissues would emerge in the near
      future. Undoubtedly, the coming 10 years should be more exciting to explore this
      "fertile" area of reproductive physiology research.

PMID- 19387873
TI  - Hemangiopericytoma-associated hypoglycemia improved by glucocorticoid therapy: a
      case report.
AB  - A 59-year-old man was admitted because of recurrent, severe hypoglycemia. He had
      multiple metastases from a meningeal hemangiopericytoma, which had been operated
      on 12 years earlier. The results of laboratory testing at the time of
      hypoglycemia showed very low serum levels of insulin, C-peptide, and growth
      hormone, with slightly high levels of insulin-like growth factor-II, and a normal
      level of insulin-like growth factor-I. The diagnosis of hemangiopericytoma
      associated hypoglycemia was proposed. The patient was given corticosteroid
      therapy, which ameliorated symptoms of hypoglycemia.

PMID- 19387874
TI  - Metformin in combination with structured lifestyle intervention improved body
      mass index in obese adolescents, but did not improve insulin resistance.
AB  - This study assessed the efficacy of adding metformin to a structured lifestyle
      intervention in reducing BMI in obese adolescents with insulin resistance. Obese
      adolescents (25) aged 10-16 years with a body mass index (BMI) > 95th percentile
      and insulin resistance (Homeostasis Model Assessment-HOMA) > 3.0 were assessed in
      a community clinic. A structured lifestyle intervention comprising nutritional
      and exercise education and motivational support in both individual and group
      sessions was delivered over 6 months. Subjects were randomized to lifestyle
      intervention alone or with metformin (1500 g daily). The primary outcome measures
      were a change in BMI and modification of metabolic risk factors, including
      insulin resistance, plasma lipids and adipocytokines. Eleven adolescents
      receiving lifestyle and metformin intervention and 14 receiving lifestyle alone
      completed the study. BMI decreased by 1.8 kg/m(2) with lifestyle and metformin
      but did not change with lifestyle alone. HOMA was significantly decreased in the
      lifestyle intervention group, but not following metformin, while the
      adiponectin/leptin ratio improved significantly in both groups. Dyslipidemic
      profiles improved most significantly with metformin. We conclude that metformin
      in combination with a 6-month structured lifestyle intervention is effective in
      reducing BMI in obese adolescents but did not improve insulin resistance.
      Lifestyle intervention, with or without metformin, improved metabolic risk
      factors such as plasma lipids and adipocytokines.

PMID- 19387876
TI  - Antifouling potential of Subtilisin A immobilized onto maleic anhydride copolymer
      thin films.
AB  - The proteinaceous nature of the adhesives used by most fouling organisms to
      attach to surfaces suggests that coatings incorporating proteolytic enzymes may
      provide a technology for the control of biofouling. In the present article, the
      antifouling (AF) and fouling release potential of model coatings incorporating
      the surface-immobilized protease, Subtilisin A, have been investigated. The
      enzyme was covalently attached to maleic anhydride copolymer thin films; the
      characteristics of the bioactive coatings obtained were adjusted through
      variation of the type of copolymer and the concentration of the enzyme solution
      used for immobilization. The bioactive coatings were tested for their effect on
      the settlement and adhesion strength of two major fouling species: the green alga
      Ulva linza and the diatom Navicula perminuta. The results show that the
      immobilized enzyme effectively reduced the settlement and adhesion strength of
      zoospores of Ulva and the adhesion strength of Navicula cells. The AF efficacy of
      the bioactive coatings increased with increasing enzyme surface concentration and
      activity, and was found to be superior to the equivalent amount of enzyme in
      solution. The results provide a rigorous analysis of one approach to the use of
      immobilized proteases to reduce the adhesion of marine fouling organisms and are
      of interest to those investigating enzyme-containing coating technologies for
      practical biofouling control.

PMID- 19387875
TI  - Increased renal Akt/mTOR and MAPK signaling in type I diabetes in the absence of
      IGF type 1 receptor activation.
AB  - Growth hormone (GH) and IGF-I have been implicated in the pathogenesis of type I
      diabetic (DM) nephropathy. We investigated renal GH receptor (GHR) and IGF-type 1
      receptor (IGF1R) signaling in an animal model of type I DM. Kidney tissue was
      examined for GHR and IGF1R key signaling molecules. GHR levels were unchanged and
      IGF-I mRNA levels were decreased in the diabetic group (D). Basal and GH
      stimulated phosphorylated (p-) JAK2 and STAT5 levels were similar in controls (C)
      and D. The levels of p-IGF1R were similar in the two groups at baseline, while
      pAkt, pGSK3, p-mTOR, p-rpS6, p-erk1/2 (Mapk), and pSTAT-3 were increased in D.
      Following IGF-I administration p-Akt, p-rpS6, p-Mapk, and p-GSK levels increased
      more pronouncedly in D versus C. In conclusion, the lack of JAK2-STAT5 activation
      and the decrease in kidney IGF-I mRNA levels in D argue against a role for the GH
      activated JAK2-STAT5 pathway in the pathogenesis of diabetic nephropathy. On the
      other hand while IGF1R phosphorylation was unchanged, Akt/mTOR and MAPK signaling
      were hyperactivate in DM, suggesting their involvement. The increase in baseline
      activated Akt, mTOR, rpS6, and MAPK cannot be explained by activation of the
      IGF1R, but may be triggered by other growth factors and nutrients.

PMID- 19387878
TI  - Visual perception in acoustically deprived and normally hearing children.
AB  - In the present study an attempt was made to establish if and to what extent
      auditory deprivation modifies the processes of visual analysis and synthesis. The
      study included 54 children aged 10-16 years with hearing impairment attending the
      School and Educational Center for Children with Hearing Impairment in Wroclaw
      (group I) and 127 children with normal hearing acuity attending public schools
      (group II), forming a reference group. Hearing impairment in the children of
      group I was from 60 to 100 dB. In 9 of these children the hearing impairment was
      inherited, while in some others it was acquired and resulted from rubella during
      the mother's pregnancy (5 subjects) or a severe disease course in childhood, for
      instance cerebral meningitis (4 subjects) and otolaryngologic antibiotic therapy
      (7 subjects). In the remaining subjects the reason for auditory deprivation was
      unknown. Hearing impairment, apart from genetically conditioned causes, appeared
      in the first months or years of life. The general intellectual level of the
      examined children was similar to that of their control counterparts, which was
      confirmed by school psychologists during a routine examination. The examination
      was performed by means of two tests from the Nonverbal Score of the Wechsler
      Intelligence Scale for Children: Puzzles and Block Design. The children with a
      hearing deficit generally needed more time to perform the tasks than those with
      normal hearing. The investigated parameters of visual perception improved in
      correlation with age, but the dynamics of these changes were different in the two
      study groups.

PMID- 19387877
TI  - Synergistic inhibition effect of tumor growth by using celecoxib in combination
      with oxaliplatin.
AB  - BACKGROUND: To evaluate the effects of celecoxib, in combination with
      oxaliplatin, on tumour growth, cell apoptosis and angiogenesis in nude mice
      models. MATERIALS AND METHODS: Xenograft mice model of colon cancer was
      established using the BALB/c nude mice. Medicine was administered respectively in
      different groups. Tumour volumes, the expression level of survivin, beta-catenin,
      VEGF mRNA level, the microvessel density and cell apoptosis were measured.
      RESULTS: Celecoxib, oxaliplatin and combination use caused a tumour inhibition of
      35%, 31% and 63% respectively. Compared with control group, a significant
      redation of angiogenesis and the levels of COX-2, survivin and beta-cantenin
      protein, and increase of cell apoptosis were detected in tumors in celecoxib
      group. Celecoxib in combination with oxaliplatin could further promote cell
      apoptosis and reduce beta-catenin protein expression. CONCLUSION: Celecoxib could
      inhibit tumor growth and enhance the antitumor effects of oxaliplatin through
      their synergistic role in inhibiting different targets.

PMID- 19387879
TI  - Depressive symptoms in climacteric women are related to menopausal symptom
      intensity and partner factors.
AB  - OBJECTIVE: To determine the prevalence of depressive symptoms and associated risk
      factors among climacteric women. METHODS: In this cross-sectional study, women
      aged 40-59 years, visiting inpatients at the Enrique C. Sotomayor Obstetrics and
      Gynecology Hospital, Guayaquil, Ecuador, were surveyed with the 17-item Hamilton
      Depression Rating Scale (HDRS), the Menopause Rating Scale (MRS) and a
      questionnaire seeking personal and partner data. RESULTS: A total of 404 women
      filled out the HDRS and the MRS. The mean age was 48.2 +/- 5.7 years; 85.1% had
      12 or less years of schooling and 44.8% were postmenopausal. None were on
      hormonal therapy for the menopause or on psychotropic drugs. The mean total HDRS
      score was 13.7 +/- 7 (median 13); this was higher among perimenopausal women. Of
      all the respondents, 78.7% had some degree of depressive symptoms (HDRS total
      score > or =8), which was mild in 32.2% and ranged from moderate to very severe
      in 46.5%. Logistic regression analysis determined that the severity of the
      menopausal symptoms related to the somatic and psychological domains of the MRS
      and the partner profile (low education and alcohol abuse) were the main
      determinants for women having higher depressive scores (total HDRS > or =8).
      CONCLUSION: In this specific climacteric population, depressive symptoms were
      very prevalent and were associated with the severity of menopausal symptoms
      (somatic and psychological) and partner's problems.

PMID- 19387880
TI  - Urogenital atrophy.
AB  - The major cause of urogenital atrophy in menopausal women is estrogen loss. The
      symptoms are usually progressive in nature and deteriorate with time from the
      menopausal transition. The most prevalent urogenital symptoms are vaginal
      dryness, vaginal irritation and itching. The classical changes in an atrophic
      vulva include loss of labial and vulvar fullness, with narrowing of the introitus
      and inflamed mucosal surfaces. Dyspareunia and vaginal bleeding from fragile
      atrophic skin are common problems. Other urogenital complaints include frequency,
      nocturia, urgency, incontinence and urinary tract infections. Atrophic changes of
      the vulva, vagina and lower urinary tract can have a large impact on the quality
      of life of the menopausal woman. However, hormonal and non-hormonal treatments
      can provide patients with the solution to regain previous level of function.
      Therefore, clinicians should sensitively question and examine menopausal women,
      in order to correctly identify the pattern of changes in urogenital atrophy and
      manage them appropriately.

PMID- 19387881
TI  - Progestin may modify the effect of low-dose hormone therapy on mammographic
      breast density.
AB  - OBJECTIVES: To evaluate the effect on breast density of two low-dose hormone
      therapy regimens identical in their estrogen component but different in the
      progestin. METHODS: A total of 81 non-hysterectomized postmenopausal women were
      allocated either to 17beta-estradiol 1 mg and norethisterone acetate 0.5 mg
      (E2/NETA, n = 43) or to 17beta-estradiol 1 mg and drospirenone 2 mg (E2/DRSP, n =
      38). Treatment was continuous and lasted 12 months. The main outcomes were the
      changes in breast density according to the Wolfe classification between baseline
      and 12-month mammograms. RESULTS: Involution of the fibroglandular tissue was not
      seen in either of the treatment groups. Under E2/NETA, breast density increased
      in seven women (16.3%). In contrast, only three women (7.9%) exhibited a density
      increase under E2/DRSP. CONCLUSIONS: Although hormone therapy appears to suspend
      breast involution, it does not increase breast density in the majority of treated
      women. Progestins differing in pharmacological properties may have a variable
      impact on breast density.

PMID- 19387882
TI  - Circulating endothelial progenitor cells in postmenopausal women with and without
      coronary artery disease.
AB  - BACKGROUND: Middle-aged women have a lower prevalence of coronary artery disease
      (CAD) compared with age-matched men, but mechanisms underlying this phenomenon
      remain controversial. To verify whether there is a link between circulating
      endothelial progenitor cells (EPCs) and gender-specific difference of CAD, we
      compared subpopulations of EPCs among postmenopausal normal women, patients with
      CAD, and age-matched men. METHODS: We studied 71 consecutive middle-aged patients
      with stable CAD (30 postmenopausal women and 41 men) and 40 middle-aged normal
      controls (20 postmenopausal women and 20 men). Blood samples were drawn at time
      of coronary angiography and subpopulations of EPCs were measured by flow
      cytometry. RESULTS: Women and men with CAD had similar age, risk factors,
      clinical presentation, left ventricular function, extension of CAD, and medical
      therapy at time of coronary angiography. Hematologic analysis showed that men and
      women with CAD had similar white cell count, mononuclear cells, and
      subpopulations of EPCs. Postmenopausal normal women, conversely, had
      significantly higher absolute numbers of CD34+, CD133+, CD105+ and CD14+ cells
      than other groups. CONCLUSIONS: Increased numbers of subpopulations of EPCs in
      normal postmenopausal women might contribute to the gender-specific difference of
      CAD in middle age. Lack of difference in EPCs between women and men with CAD
      suggests that stem cells become unable to play a protective role when the disease
      is clinically evident.

PMID- 19387883
TI  - Pharmacology and clinical applications of selective estrogen receptor modulators.
AB  - Compounds that can be described as selective estrogen receptor modulators (SERMs)
      have expanded dramatically over the past two decades. The ability of SERMs to act
      as estrogens in certain tissues while remaining inert or acting as an anti
      estrogen in other tissues has opened up opportunities for treating specific
      estrogen-modulated diseases without accepting the risk of systemic estrogen
      activity. SERM development has resulted in significant therapeutic advances for
      breast cancer, osteoporosis and potentially other diseases associated with the
      menopause. After the publication of the Women's Health Initiative, interest in
      compound selectivity that reduces menopausal symptoms while protecting bone,
      breast, uterus and the heart has increased. Future SERMs may also have a
      therapeutic profile that can be tailored to specific patient populations,
      including men. This review paper summarizes the characteristics of different
      SERMs from various pharmacological categories and the feasibility and scope of
      their use for a large range of disease/health conditions.

PMID- 19387884
TI  - Postmenopausal hormone therapy with estradiol and norethisterone acetate and
      mammographic density: findings from a cross-sectional study among Norwegian
      women.
AB  - BACKGROUND: Although a number of studies have evaluated the associations between
      use of postmenopausal hormone therapy (HT) and mammographic density, few have
      assessed the effects of the medications containing estradiol (E2) plus
      norethisterone acetate (NETA). In particular, there are few data on the effects
      of the low-dose E2/NETA regimen. METHODS: We included data from 724 women, aged
      50-70 years, residing in south-east Norway, who participated in a cross-sectional
      study conducted within the Norwegian Breast Cancer Screening Program. We assessed
      mammographic density using a previously validated computer-assisted method.
      RESULTS: After adjusting for age at screening, number of children and body mass
      index, women who currently used HT had 6.0% higher percent mammographic density
      than never-users, p < 0.0001. Women who used either low- or high-dose continuous
      combined E2/NETA regimens had 7.7% (p < 0.0001) and 8.8% (p < 0.0001) higher
      percent mammographic density than never-users, respectively. CONCLUSION: Our
      study suggests that the effect of E2/NETA regimens on mammographic density could
      be at least as detrimental to the breast tissue as several other estrogen +
      progestin regimens. Our results suggest that both low- and high-dose E2/NETA
      influence mammographic density, but there were some indications in our analyses
      that the effect of low-dose E2/NETA could be slightly lower than that of the
      older high-dose regimen.

PMID- 19387885
TI  - Extraembryonic tissues as a source of stem cells.

PMID- 19387888
TI  - Laboratory evaluation of a field-portable sealed source X-ray fluorescence
      spectrometer for determination of metals in air filter samples.
AB  - Recent advances in field-portable X-ray fluorescence (FP XRF) spectrometer
      technology have made it a potentially valuable screening tool for the industrial
      hygienist to estimate worker exposures to airborne metals. Although recent
      studies have shown that FP XRF technology may be better suited for qualitative or
      semiquantitative analysis of airborne lead in the workplace, these studies have
      not extensively addressed its ability to measure other elements. This study
      involved a laboratory-based evaluation of a representative model FP XRF
      spectrometer to measure elements commonly encountered in workplace settings that
      may be collected on air sample filter media, including chromium, copper, iron,
      manganese, nickel, lead, and zinc. The evaluation included assessments of (1)
      response intensity with respect to location on the probe window, (2) limits of
      detection for five different filter media, (3) limits of detection as a function
      of analysis time, and (4) bias, precision, and accuracy estimates. Teflon,
      polyvinyl chloride, polypropylene, and mixed cellulose ester filter media all had
      similarly low limits of detection for the set of elements examined. Limits of
      detection, bias, and precision generally improved with increasing analysis time.
      Bias, precision, and accuracy estimates generally improved with increasing
      element concentration. Accuracy estimates met the National Institute for
      Occupational Safety and Health criterion for nearly all the element and
      concentration combinations. Based on these results, FP XRF spectrometry shows
      potential to be useful in the assessment of worker inhalation exposures to other
      metals in addition to lead.

PMID- 19387886
TI  - Identifying language impairment in children: combining language test scores with
      parental report.
AB  - BACKGROUND: Children who meet language test criteria for specific language
      impairment (SLI) are not necessarily the same as those who are referred to a
      speech and language therapist. AIMS: To consider how far this discrepancy
      reflects insensitivity of traditional language tests to clinically important
      features of language impairment. METHODS & PROCEDURES: A total of 245 twin
      children, 52 of whom had been referred to a speech and language therapist for
      assessment or intervention, were studied. They were given a battery of language
      tests and their parents completed the Children's Communication Checklist - 2 (CCC
      2). RESULTS: Language tests that stressed verbal short-term memory were best at
      distinguishing clinically referred from other cases; narrative and vocabulary
      tasks were less effective. A discriminant function analysis identified a
      combination of language test and parental report measures as giving the best
      discrimination between referred and non-referred cases. Nevertheless, of 82
      children classified as language impaired by the discriminant function, 44 had
      never been referred to a speech and language therapist. These did not appear to
      be false-positives; they scored at least as poorly as referred cases on literacy
      tests. They had significantly lower socio-economic backgrounds than referred
      cases. CONCLUSIONS & IMPLICATIONS: Language test scores provide important
      information about which children are at risk of academic failure, though this
      varies from test to test. Reliance on language tests alone, however, is
      insufficient; a parental report provides important complementary information in
      the diagnostic process. Children of low socio-economic status with language
      problems are particularly likely to have no contact with speech and language
      therapist services.

PMID- 19387889
TI  - Distal and proximal influences on the risk of extramarital sex: a prospective
      study of longer duration marriages.
AB  - Previous models of the risk of extramarital sex (EMS) rely largely on cross
      section samples and retrospective reporting. This may well conflate causes with
      consequences of EMS in the same model. Instead, this study employs panel data
      with an event-history approach to re-assess the influences on the risk of EMS.
      The sample consists of 1,270 married respondents, with no prior history of EMS,
      who were followed up in five subsequent surveys spanning a 20-year period. The
      quality of the conjugal bond emerged as a paramount influence on the outcome. The
      hazard of EMS was higher for respondents who had ever experienced a trial
      separation, reported marital violence, scored higher on a marital instability
      index, or spent less time in activities with the spouse. The risk of EMS was
      lower the longer respondents had been married at baseline, the longer the
      duration since baseline, and the greater the respondent's religiosity.

PMID- 19387891
TI  - Variation in glucuronidation of lamotrigine in human liver microsomes.
AB  - Lamotrigine (LTG), a diaminotriazine anti-epileptic, is principally metabolized
      at the 2-position of the triazine ring to form a quaternary ammonium glucuronide
      (LTGG) by uridine glucuronosyl transferease (UGT) 1A3 and UGT1A4. It has been
      hypothesized that glucuronidation of anti-epileptic drugs is spared with age,
      despite a known decrease in liver mass, based on older studies with
      benzodiazepines such as lorazepam. To examine this, the formation rates of LTGG
      formation were measured by liquid chromatography-mass spectrometry (LC-MS) in a
      bank of human liver microsomes (HLMs) obtained from younger and elderly donors at
      therapeutic concentrations. The formation rate of LTGG was not significantly
      different in HLMs obtained from younger and elderly subjects. A four- to five
      fold variation for the formation of LTGG was observed within each microsomal bank
      obtained from elderly and younger donors, and the range of LTGG formation was
      observed to be 0.15-0.78 nmoles min(-1) mg(-1) of protein across the entire set
      of HLMs (n = 36, elderly and younger HLMs). UGT1A4 and UGT1A3 catalysed the
      formation of LTGG with an intrinsic clearances of 0.28 and 0.02 microl min(-1)
      mg(-1) protein, respectively. UGT2B7 and UGT2B4 showed no measurable activity. No
      correlation was observed across the HLM bank for glucuronidation of LTG and
      valproic acid (a substrate for multiple UGT isoforms including UGT1A4).

PMID- 19387892
TI  - Dialkyl phosphates in meconium as a biomarker of prenatal exposure to
      organophosphate pesticides: a study on pregnant women of rural areas in Crete,
      Greece.
AB  - The authors developed a sensitive analytical method for the determination of
      dialkyl phosphates (DAPs) in meconium. This method was applied to determine the
      DAPs, which are non-specific metabolites of the organophosphate pesticides (OPs),
      in meconium of newborns by mothers who live in rural areas in Crete, Greece. DAPs
      are considered as biomarkers of exposure to OPs. Meconium is produced in the
      foetus at approximately 16 weeks of gestation and it acts as a repository of many
      xenobiotics. The determined organophosphate metabolites were dimethylphosphate
      (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP), diethylthiophosphate
      (DETP), and diethyldithiophosphate (DEDTP). The DAPs were extracted from meconium
      by liquid-solid extraction, derivatized, and analysed by gas chromatography-mass
      spectrometry (GC-MS). The mean percentile recoveries were 76.9%, 65.2%, 94.1%,
      109.4%, and 107.2% for DMP, DEP, DMTP, DETP, and DEDTP, respectively. The
      percentage of positive samples was 92.1% for DMP, 36.8% for DEP, 60.5% for DMTP,
      63.2% for DETP, and 57.9% for DEDTP. Mean (+/- standard deviation) and the range
      concentrations of the positive samples (ng g(-1)) were 126.74 +/- 142.73 (10.64
      739.45), 11.46 +/- 20.43 (1.50-79.14), 215.05 +/- 187.34 (8.54-662.16), 4.92 +/-
      5.09 (1.25-19.04), and 1.84 +/- 2.07 (0.5-8.04) for DMP, DEP, DMTP, DETP, and
      DEDTP, respectively. Statistical analysis revealed no significant difference in
      meconium levels between high- and low-risk groups of exposure of pregnant women.
      However, the results of this study demonstrate that DAPs in meconium may be
      considered as a potential biomarker for the assessment of foetal exposure to
      organophosphate pesticides.

PMID- 19387894
TI  - Proceedings of the 9th Japanese Annual Conference on Chronocardiology and
      Hypertension. 2007.

PMID- 19387893
TI  - Hydroxylation of tanshinone IIa in human liver microsomes is specifically
      catalysed by cytochrome P4502A6.
AB  - Tanshinone IIa, the primary active component of a traditional Chinese medicine
      Salvia miltiorrhiza (Danshen), has a wide range of pharmacological activities. In
      the present study, the metabolism of tanshinone IIa (5 microM) by cytochrome
      P450s (CYPs) was investigated in human liver microsomes. One mono-hydroxylated
      metabolite was detected in a reaction catalysed by human liver microsomes, and
      was identified as tanshinone IIb by comparing the tandem mass spectra and the
      chromatographic retention time with that of the standard compound. The study with
      a chemical selective inhibitor, cDNA-expressed human cytochrome P450s,
      correlation assay, and kinetics study demonstrated that CYP2A6 was the specific
      isozyme responsible for the hydroxyl metabolism of tanshinone IIa (5 microM) in
      human liver microsomes.

PMID- 19387895
TI  - Evaluation of carotid atherosclerosis from the perspective of blood flow
      reflection.
AB  - Detection and prevention of atherosclerosis at an early stage is important for
      its prevention. The aim of this study was to propose a valid and highly reliable
      index for the evaluation of carotid atherosclerosis or carotid function. Images
      of carotid Doppler wave profiles were processed using an image processing
      software, and the relative fluctuation in blood flow was calculated from the
      luminance in one cardiac cycle. Frequency analysis was performed and up to 10
      time components of basic frequency (f1) were indicated. The evaluation function
      alpha was estimated by calculating the ratio of the sum of components f3-f10
      against the f1 + f2 components. Blood pressure of the finger was continuously
      measured using Finapress during passive postural change from the supine to the
      standing position, the baroreceptor function was evaluated by the frequency
      method, and the plaque score was measured by ultrasound tomography. The influence
      of factors such as arterial compliance, blood vessel resistance, and heart rate
      on this index was studied using electric circuit model simulation. The subjects
      were 33 patients (18 men, 15 women) who had various types of atherosclerotic
      disease and hypertension. The average age was 67.3 + 12.2 years. The results
      showed that index alpha had a strong negative correlation with age and plaque
      score, and a weak positive correlation with baroreceptor function. Simulation
      results supported the clinical result. We proposed a new index to evaluate
      carotid atherosclerosis without blood pressure measurement using the carotid
      Doppler method. It is a potential index for detecting atherosclerosis of local
      arteries such as the carotid.

PMID- 19387896
TI  - Clock gene expression in the liver and adipose tissues of non-obese type 2
      diabetic Goto-Kakizaki rats.
AB  - Recent studies have revealed a close relationship between the pathophysiology of
      metabolic syndrome, which is characterized by obesity and hyperglycemia, and the
      functioning of internal molecular clocks. In this study, we show that the
      rhythmic mRNA expression of clock genes (Clock, Bmal1, Cry1, and Dbp) is not
      attenuated in the liver and visceral adipose tissues of Goto-Kakizaki rats, a
      model of nonobese, type 2 diabetes, as compared to control Wistar rats. Our
      results suggest that molecular clock impairment in peripheral tissues of obese
      diabetic animals may be either caused by obesity-related factor(s), but not
      hyperglycemia, or be a cause, but not a consequence, of hyperglycemia.

PMID- 19387897
TI  - Plasminogen activator inhibitor-1 and the circadian clock in metabolic disorders.
AB  - Plasma PAI-1 levels robustly fluctuate in a circadian manner and consequently
      contribute to hypofibrinolysis during the early morning. The circadian expression
      of PAI-1 gene is thought to be directly regulated by the circadian clock proteins
      such as CLOCK and BMAL1/BMAL2 which drive the endogenous biological clock. Plasma
      PAI-1 levels are increased in the beginning of the active phase in both diurnal
      humans and in nocturnal rodents, suggesting that the rhythmic PAI-1 expression is
      commonly indispensable for organisms. A series of our recent studies revealed
      that circadian clock proteins are important for hypofibrinolysis induced by
      metabolic disorders such as obesity and diabetes.

PMID- 19387898
TI  - Time for reflection predicts the progression of renal dysfunction in patients
      with nondiabetic chronic kidney disease.
AB  - Our previous data indicated that both home blood pressure and arterial stiffness
      predicted the progression of renal dysfunction in the patients with chronic
      kidney diseases. In the present study, we examined both home blood pressure and
      the parameters of arterial stiffness as the indicator to the progression of
      chronic kidney diseases. Forty-two nondiabetic chronic kidney disease patients
      were enrolled and followed for 1 year. Anti-hypertensive therapy was adjusted to
      achieve office blood pressure below 130/80 mmHg. Home blood pressure was examined
      twice a day in the morning and evening. Pulse wave velocity (PWV) and
      augmentation index (AI) were measured as the index of arterial stiffness. The
      time for reflection (TR) was also determined. The relationship of annual changes
      in serum creatinine (Scr) with the above parameters was assessed. Multivariate
      regression analysis revealed that TR inversely correlated to annual increase in
      Scr (beta = -0.03, p < 0.05). Home blood pressure did not correlate to annual
      changes in Scr in the present study. The present data indicated that arterial
      stiffness is elevated despite good blood pressure control in chronic kidney
      disease, especially among the dippings. In addition, our data suggest that PWV
      and AI correlated to each other, while they were influenced differently by
      hemodynamic factors. Finally, the present findings provide the evidence that the
      arterial stiffness parameter is more sensitive than home blood pressure as an
      indicator to the progression of chronic kidney disease.

PMID- 19387899
TI  - Weight loss and blood pressure reduction in obese subjects in response to
      nutritional guidance using information communication technology.
AB  - The metabolic syndrome caused by visceral-fat obesity is a major risk factor for
      atherosclerosis. This study used a new information communication technology (ICT)
      to investigate body weight (BW) and blood pressure (BP) changes in response to
      nutritional guidance. Obese subjects with hypertension, hyperlipidemia, or
      impaired glucose tolerance received guidance with the ICT method (n = 13) or face
      to-face according to conventional methods (n = 39). The effects of the methods
      were compared. After 12 weeks, significant weight loss and BP reduction were
      observed in the ICT group. Also, significant higher improvements were observed in
      total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and HbA(1c) in
      the ICT-group compared with those groups using the conventional method. The
      effectiveness of the ICT method in reducing BW, BP, total and LDL cholesterol,
      and HbA(1c) was demonstrated.

PMID- 19387900
TI  - Cilnidipine inhibits the sympathetic nerve activity and improves baroreflex
      sensitivity in patients with hypertension.
AB  - N-type calcium channel blocker, cilnidipine, is reported not to increase the
      heart rate in spite of the strong depressor effect. However, it has not been
      determined whether cilnidipine has the sympatho-inhibitory effects or not.
      Moreover, the effect of cilnidipine on the baroreflex control has not been
      determined. The aim of this study was to determine the effect of cilnidipine on
      sympathetic and parasympathetic nerve activity, and baroreflex sensitivity. We
      studied five hypertensive patients treated with 10 mg cilnidipine (10-mg group)
      and five hypertensive patients treated with 20 mg cilnidipine (20-mg group).
      Before the treatment and 6 months after the treatment, we measured the blood
      pressure, spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV),
      and blood pressure variability (BPV). After 6 months, systolic blood pressure
      (SBP) and the low-frequency component of systolic BPV expressed in normalized
      units (LFnuSBP), as the parameter of sympathetic nerve activity, was
      significantly decreased in both groups, and the suppressive effects were stronger
      in the 20-mg group than in the 10-mg group. The high-frequency component of HRV
      expressed in normalized units, as the parameter of parasympathetic nerve
      activity, and BRS were significantly increased in 20-mg group, but not
      significant in 10-mg group. These results suggest that 6 months treatment with
      cilnidipine for hypertension has the sympatho-inhibtory effect, and that high
      dose cilnidipine improves the parasympathetic nerve activity and baroreflex
      control in patients with hypertension.

PMID- 19387901
TI  - Effects of angiotensin II receptor blockers on relationships between 24-hour
      blood pressure, autonomic function, and health-related QOL.
AB  - We report the relationship between 24-hour (24-h) blood pressure, autonomic
      function, and health-related quality of life (HRQOL) in normotensives and
      hypertensives. The aim of this study was to determine whether there is a
      relationship between 24-h blood pressure, autonomic function, and HRQOL during
      treatment with an angiotensin receptor blocker (ARB) in patients with
      hypertension. Thirteen patients with hypertension were randomly treated with
      losartan (25-50 mg, n = 5), candesartan (4-8 mg, n = 4), valsartan (80 mg, n =
      1), telmisartan (40 mg, n = 2), and olmesartan (10 mg, n = 1), daily. 24-h
      ambulatory blood pressure (BP) was measured before treatment and 3 months after
      treatment. Sympathetic nervous activity (the ratio of low frequency to high
      frequency component (LF/HF)) and parasympathetic nervous activity (high frequency
      component (HF)) were calculated by analyzing heart rate variability. HRQOL was
      assessed using a medical outcome study short-form 36-item health survey (SF-36)
      questionnaire. All of the participants completed the study. Angiotensin receptor
      blocker treatment reduced 24-h mean BP (MBP) from 107 +/- 9 to 100 +/- 9 mmHg. 24
      h MBP positively correlated with 24-h LF/HF in all subjects who received ARB (R =
      0.568, p < 0.04). There were no differences in heart rate, serum albumin level,
      BUN level, creatinine level, potassium level, or HRQOL score. These findings
      indicated that ARB reduced BP; however, treatment with ARB did not affect the
      scores of HRQOL and the relationship between 24-h blood pressure and autonomic
      function.

PMID- 19387902
TI  - Identification of an increased short-term blood pressure variability on
      ambulatory blood pressure monitoring as a coronary risk factor in diabetic
      hypertensives.
AB  - We examined risk factors for coronary heart disease (CHD) by ambulatory blood
      pressure (BP) monitoring in 72 diabetic hypertensives who were hospitalized for
      the educational program. The patients were divided into two groups (CHD group, 19
      subjects; and non-CHD group, 53 subjects) along with or without co-existing CHD.
      On ambulatory BP monitoring, no significant differences were found between the
      groups regarding BP values through the day. However, the CHD group had a
      significantly greater BP variability than non-CHD group. The result of logistic
      regression analysis demonstrated that nighttime systolic BP variability was an
      independent risk factor for CHD.

PMID- 19387903
TI  - High salt intake elevated blood pressure but not changed circadian blood pressure
      rhythm in Otsuka Long-Evans Tokushima Fatty (OLETF) rat.
AB  - We examined the effect of high salt intake on mean arterial pressure and
      circadian blood pressure rhythm in Otsuka Long-Evans Tokushima Fatty (OLETF)
      rats, a model of type II diabetes mellitus. Mean arterial pressure, fasting blood
      glucose, and fasting plasma insulin in OLETF rats were higher than those in LETO
      rats, their normoglycemic controls. The amplitude of circadian blood pressure
      rhythm in LETO rats was smaller than that in OLETF rats. High salt intake
      elevated blood pressure and exacerbated hyperinsulinemia, but did not change the
      circadian blood pressure rhythm in OLETF rats.

PMID- 19387904
TI  - Role of inducible nitric oxide synthase in rostral ventrolateral medulla in blood
      pressure regulation in spontaneously hypertensive rats.
AB  - Nitric oxide (NO) in the brainstem modulates blood pressure (BP). Overexpression
      of inducible NO synthase (iNOS) in the rostral ventrolateral medulla (RVLM)
      increases BP in normotensive Wistar-Kyoto rats (WKY), but its role in BP
      regulation in spontaneously hypertensive rats (SHR) is unknown. We examined iNOS
      expression and the effect of iNOS inhibitors in the RVLM on BP and heart rate in
      SHR and WKY. iNOS levels in the RVLM were significantly higher in SHR than in
      WKY. Bilateral microinjection of aminoguanidine into the RVLM dose-dependently
      decreased BP and heart rate in SHR, but not in WKY. These findings suggest that
      iNOS expression in the RVLM of SHR contributes to increase BP.

PMID- 19387905
TI  - Possibilities and limits of Internet-based registers.
AB  - The Internet is an inexpensive platform for the investigation of medical
      questions in case of low prevalence. By accessing www.ao-nailregister.org, every
      interested participant may participate in the English-language survey of the
      complications specific to the femoral nail. The address data of the participant,
      the anonymised key data of the patients and the medical parameters are entered.
      In real time, these data are checked for plausibility, evaluated and published on
      the Internet where they are freely accessible immediately. Because of national
      differences, data acquisition caused considerable difficulties at the beginning.
      In addition, wrong data were entered because of linguistic or contextual
      misunderstandings. After having reworked the questionnaire completely,
      facilitating data input and implementing an automated plausibility check, these
      difficulties could be cleared. In a next step, the automatic evaluation of the
      data was implemented. Only very few data still have to be checked for
      plausibility manually to exclude wrong entries, which cannot be verified by the
      computer. The effort required for data acquisition and evaluation of the Internet
      based femoral nail register was reduced distinctly. The possibility of free
      international participation as well as the freely accessible representation of
      the results offers transparency.

PMID- 19387906
TI  - Interprofessional education for students of the health professions: the "Seamless
      Care" model.
AB  - "Seamless Care" was one of 21 grants awarded by Health Canada to inform
      policymakers of the effectiveness of interprofessional education in promoting
      collaborative patient-centred practice among health professionals. The "Seamless
      Care" model of interprofessional education was designed with input from three
      Faculties at Dalhousie University (Medicine, Dentistry and Health Professions).
      The design was grounded in relevant learning theories--Social Cognitive Theory,
      Self-efficacy, Situated Learning theory and Constructivism. The intervention was
      informed by principles of active learning, problem-based learning, reflection and
      role modeling. The primary goal of Seamless Care was to develop students'
      interprofessional patient-centred collaborative skills through experiential
      learning. Fourteen student teams, each including one student from medicine,
      nursing, pharmacy, dentistry and dental hygiene, learned with, from and about
      each other while they were mentored in the collaborative care of patients
      transitioning from acute care to the community. Student teams providing
      collaborative care assisted patients experiencing a chronic illness to become
      more active in managing their health through development of self-management and
      decision-making skills. This paper describes the Seamless Care model of
      interprofessional education and discusses the theoretical underpinnings of this
      experiential model of interprofessional education designed to extend classroom
      based interprofessional education to the clinical setting.

PMID- 19387907
TI  - Interprofessional intensive care unit team interactions and medical crises: a
      qualitative study.
AB  - Research has suggested that interprofessional collaboration could improve patient
      outcomes in the intensive care unit (ICU). Maintaining optimal interprofessional
      interactions in a setting where unpredictable medical crises occur periodically
      is however challenging. Our study aimed to investigate the perceptions of ICU
      health care professionals regarding how acute medical crises affect their team
      interactions. We conducted 25 semi-structured interviews of ICU nurses, staff
      physicians, and respiratory therapists. All interviews were audio-taped and
      transcribed, and the analysis was undertaken using an inductive thematic
      approach. Our data indicated that the nature of interprofessional interactions
      changed as teams passed through three key temporal periods around medical crises.
      During the "pre-crisis period", interactions were based on the mutual respect of
      each other's expertise. During the "crisis period", hierarchical interactions
      were expected and a certain lack of civility was tolerated. During the "post
      crisis period", divergent perceptions emerged amongst health professionals. Post
      crisis team dispersion left the nurses with questions and emotions not expressed
      by other team members. Nurses believed that systematic interprofessional feedback
      sessions held immediately after a crisis could address some of their needs.
      Further research is needed to establish the possible benefits of strategies
      addressing ICU health care professionals' specific needs for interprofessional
      feedback after a medical crisis.

PMID- 19387908
TI  - Perceptions of interprofessional collaboration within child mental health care in
      Norway.
AB  - The present study investigates professionals' perceptions of interprofessional
      collaboration (IPC) in the field of mental health care for children and
      adolescents. In this study, a 48-item questionnaire was developed to measure
      perceptions of interprofessional collaboration. A theoretical model (PINCOM) is
      presented and suggests that interprofessional collaboration is perceived at the
      individual-, group- and organizational level. The questionnaire was distributed
      to a sample consisting of 157 professionals in Western Norway. The results of
      this exploratory study show that the most prominent constructs of collaboration
      perceived by the professionals were: motivation, group leadership, social support
      and organizational culture. Furthermore, results indicate that women are more
      oriented than men toward IPC aspects of communication, coping and organizational
      domain. It is suggested that the questionnaire may be used to help improve
      interprofessional collaboration in clinical practice by indicating new ways to
      enhance dialogue between professionals and to investigate changes in perception
      of interprofessional collaboration over time. Limitations of the present study
      were identified and suggestions for future studies within the field are provided.

PMID- 19387911
TI  - Teamwork: a study of Australian and US student speech-language pathologists.
AB  - In the discipline of speech-language pathology little is known about the explicit
      and implicit team skills taught within university curricula. This study surveyed
      281 speech-language pathology students to determine a baseline of their perceived
      ability to participate in interprofessional teams. The students were enrolled in
      programs in Australia and the USA and were surveyed about their perceptions of
      their attitudes, knowledge and skills in teamwork. MANCOVA analysis for main
      effects of age, university program and clinical experience showed that age was
      not significant, negating the perception that life experiences improve perceived
      team skills. Clinical experience was significant in that students with more
      clinical experience rated themselves more highly on their team abilities. Post
      Hoc analysis revealed that Australian students rated themselves higher than their
      US counterparts on their knowledge about working on teams, but lower on attitudes
      to teams; all students perceived that they had the skills to work on teams. These
      results provide insight about teamwork training components in current speech
      language pathology curricula. Implications are discussed with reference to
      enhancing university training programs.

PMID- 19387912
TI  - Cost effective interprofessional training: an evaluation of a training unit in
      Denmark.
AB  - In 2004, the first Danish undergraduate interprofessional training unit (ITU) was
      established at the Regional Hospital Holstebro, inspired by experiences from
      Sweden. In this unit, medical, nursing, occupational therapy and physiotherapy
      students are given responsibility, under supervision by trained and motivated
      personnel, for rehabilitation and care of patients in a subunit of an orthopaedic
      department. The aim of this study was to see whether the ITU was cost effective
      in treating patients compared with a conventional orthopaedic ward. One-hundred
      and thirty-four patients admitted for primary hip or knee replacement surgery
      were included in the study. All costs were recorded in the ITU and in the
      conventional ward. Follow-up was done by a quality of life questionnaire three
      months after the operation. Comparison was done by univariable and multivariable
      testing of costs and effect. In both, the ITU was more cost effective than the
      conventional ward. No difference was found in complications and patient-reported
      quality of life. In conclusion, clinical training can be given to students in an
      ITU without reducing productivity in a hospital environment if pedagogic
      principles, clinical tutors and patient logistics all adapt to the challenge of
      the teaching environment.

PMID- 19387913
TI  - Alcohol and liver disease.

PMID- 19387914
TI  - Oxidative stress and alcoholic liver disease.
AB  - Reactive oxygen species (ROS) are highly reactive molecules that are naturally
      generated in small amounts during the body's metabolic reactions and can react
      with and damage complex cellular molecules such as lipids, proteins, or DNA. This
      review describes pathways involved in ROS formation, why ROS are toxic to cells,
      and how the liver protects itself against ROS. Acute and chronic ethanol
      treatment increases the production of ROS, lowers cellular antioxidant levels,
      and enhances oxidative stress in many tissues, especially the liver. Ethanol
      induced oxidative stress plays a major role in the mechanisms by which ethanol
      produces liver injury. Many pathways play a key role in how ethanol induces
      oxidative stress. This review summarizes some of the leading pathways and
      discusses the evidence for their contribution to alcohol-induced liver injury.

PMID- 19387915
TI  - Alcoholic liver disease and methionine metabolism.
AB  - Alcoholic liver disease is a major health care problem worldwide. Findings have
      demonstrated that ethanol feeding impairs several of the multiple steps in
      methionine metabolism that leads to progressive liver injury. Ethanol consumption
      has been reported to predominantly inhibit the activity of a vital cellular
      enzyme, methionine synthase, involved in remethylating homocysteine. By way of
      compensation in some species, ethanol can also increase the activity of the
      enzyme, betaine homocysteine methyltransferase. This enzyme catalyzes an
      alternate pathway in methionine metabolism and utilizes hepatic betaine to
      remethylate homocysteine to form methionine and maintain levels of S
      adenosylmethionine, the key methylating agent. Under extended periods of ethanol
      feeding, however, this alternate pathway cannot be maintained. This results in a
      decrease in the hepatocyte level of S-adenosylmethionine and increases in two
      toxic metabolites, S-adenosylhomocysteine and homocysteine. These changes in the
      various metabolites of methionine metabolism, in turn, result in serious
      functional consequences. These include decreases in essential methylation
      reactions by inhibiting various methyltransferases critical to normal functioning
      of the liver and upregulation of the activation of endoplasmic reticulum
      dependent apoptosis and lipid synthetic pathways. The ultimate outcome of these
      consequences is increased fat deposition, increased apoptosis, accumulation of
      damaged proteins, and alterations in various signaling pathways, all of which can
      ultimately result in progressive liver damage. Of all the therapeutic modalities
      that are presently being used to attenuate ethanol-induced liver injury, betaine
      has been shown to be the most effective in a variety of experimental models of
      liver disease. Betaine, by virtue of aiding in the remethylation of homocysteine,
      removes both toxic metabolites (homocysteine and S-adenosylhomocysteine),
      restores S-adenosylmethionine level, reverses steatosis, prevents apoptosis and
      reduces both damaged protein accumulation and oxidative stress. Thus, betaine is
      a promising therapeutic agent in relieving the methylation and other defects
      associated with alcoholic abuse.

PMID- 19387916
TI  - Alcohol-induced modulation of signaling pathways in liver parenchymal and
      nonparenchymal cells: implications for immunity.
AB  - Alcoholic liver injury involves a complex array of derangements in cellular
      signaling of hepatic parenchymal and nonparenchymal cells as well as cells of the
      immune system. In the hepatocyte, chronic ethanol abuse leads to lipid
      accumulation and liver steatosis. Multiple pathways are affected to promote lipid
      accumulation in the ethanol-exposed hepatocyte. Chronic ethanol renders Kupffer
      cells hyperresponsive to endotoxin, which results in production of inflammatory
      cytokines and the tumor necrosis factor-alpha via a toll-like receptor 4
      dependent pathway, leading to inflammation and hepatic necrosis. Dysfunction of
      the innate and adaptive immune responses caused by ethanol contributes to
      impaired antiviral response, inflammatory injury, and autoimmune activation.
      Recent developments in the literature are reviewed in a model that suggests lipid
      accumulation, dysregulation of immunity, and impaired antiviral and autoimmune
      responses as three distinct, though interwoven, pathophysiological mechanisms of
      alcoholic liver injury.

PMID- 19387917
TI  - "Second hit" models of alcoholic liver disease.
AB  - Alcoholic liver disease (ALD) is a lifestyle disease with its pathogenesis and
      individual predisposition governed by gene-environment interactions. Based on the
      "second hit" or "multiple hits" hypothesis, patients are predisposed to
      progressive ALD when a magic combination of gene and environmental interactions
      exists. Reproduction of second or multiple hits in animal models serves to test a
      combination and to gain mechanistic insights into synergism achieved by such
      combination. Numerous environmental factors have been incorporated into animal
      models, largely classified into nutritional, xenobiotic/pharmacologic,
      hemodynamic, and viral groups. A loss or gain of function genetic model has
      become a popular experimental approach to test the role of a gene as a second
      hit. Future research will need to test more subtle or natural hits combined with
      excessive alcohol intake to test multiple hits in the genesis of ALD.
      Additionally, animal models of comorbidities are urgently needed particularly for
      synergistic liver disease and oncogenesis caused by alcohol, obesity, and
      hepatitis virus.

PMID- 19387918
TI  - Hepatitis C virus and alcohol.
AB  - This review will focus on the prevalence of hepatitis c virus (HCV) infection in
      alcoholics with and without liver disease. Evidence will be presented to
      demonstrate that ethanol and chronic HCV infection synergistically accelerate
      liver injury. Some of the major postulated mechanisms responsible for disease
      progression include high rates of apoptosis, lipid peroxidation, and generation
      of free radicals and reactive oxygen species with reduced antioxidant capacity of
      the liver. Acquisition and persistence of HCV infection may be due to the adverse
      effects of ethanol on humoral and cellular immune responses to HCV. Dendritic
      cells (DC) appear to be one of the major targets for ethanol's action and DC
      dysfunction impairs the ability of the host to generate viral specific cluster of
      differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) immune
      responses. There is a relationship between increased alcohol intake and decreased
      response to interferon (IFN) therapy, which may be reversed by abstinence.
      Clinical studies are needed to optimize treatment responses in alcoholic patients
      with chronic HCV infection.

PMID- 19387920
TI  - Alcohol and liver fibrosis.
AB  - Alcoholic liver disease involves significant crosstalk among intracellular
      signaling events in the liver. Overall, inflammatory and innate immune responses
      in Kupffer cells due to elevated gut-derived plasma endotoxin levels, increased
      reactive oxygen species-induced damage, and profibrogenic factors such as
      acetaldehyde or lipid peroxidation products contribute to activation of hepatic
      stellate cells, the key cell type involved in liver fibrosis. Using in vitro and
      in vivo approaches, there has been great progress in our understanding of the
      mechanisms leading to liver fibrosis: potential biomarkers of fibrosis have been
      identified, and several candidate targets for antifibrotic drugs have been
      elucidated.

PMID- 19387921
TI  - Role of alcohol in liver carcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the
      world and contributes significantly to cancer-related morbidity and mortality.
      Chronic alcohol consumption has long been associated with progressive liver
      disease toward the development of hepatic cirrhosis and the subsequent increased
      risk for developing HCC. In assessing the role of alcohol during hepatic disease,
      and as a carcinogen, many of the deleterious effects of alcohol can be attributed
      to alcohol metabolism in hepatocytes. In addition to the direct effects of
      alcohol/alcohol metabolism on hepatocyte transformation, increasing evidence
      indicates that other intrahepatic and systemic effects of alcohol are likely to
      play an equally significant role in the process of hepatic tumorigenesis.

PMID- 19387919
TI  - Similarities and differences in the pathogenesis of alcoholic and nonalcoholic
      steatohepatitis.
AB  - Subpopulations of individuals with alcohol-induced fatty livers and nonalcoholic
      steatosis develop steatohepatitis. Steatohepatitis is defined histologically:
      increased numbers of injured and dying hepatocytes distinguish this condition
      from simple steatosis. The increased hepatocyte death is generally accompanied by
      hepatic accumulation of inflammatory cells and sometimes increases in
      myofibroblastic cells, leading to hepatic fibrosis and eventually, cirrhosis. The
      purpose of this review is to summarize similarities and differences in the
      pathogenesis of steatohepatitis in alcoholic fatty liver disease and nonalcoholic
      fatty liver disease.

PMID- 19387922
TI  - Patient with hepatitis B and alcoholic liver disease before and after liver
      transplantation.
AB  - We present the case of a patient with hepatitis B virus infection and alcohol use
      (30 g/day by self-report) who developed cirrhosis and proceeded to liver
      transplantation at age 49. The explanted liver showed cirrhosis with evidence of
      burnt-out steatohepatitis and hepatitis B virus and a 0.7-cm focus of well
      differentiated hepatocellular carcinoma. He was managed following transplant with
      tacrolimus, prednisone, lamivudine, adefovir, and hepatitis B immune globulin
      infusions. His post-transplant course was complicated by several episodes of
      elevated liver enzymes. Liver biopsy 3 months after liver transplantation showed
      acute rejection and mild steatohepatitis. Liver biopsy 6 months after liver
      transplantation showed marked steatosis (approximately 95%) with moderate
      steatohepatitis and evidence of treated rejection. Subsequent biopsies (15 and 21
      months post liver transplantation) showed resolution of the steatohepatitis, but
      development of chronic rejection. We discuss the interaction of alcoholic liver
      disease and hepatitis B virus in the development of cirrhosis and hepatocellular
      carcinoma, as well as the role of liver transplantation in these patients.

PMID- 19387923
TI  - Carbon dioxide, hypoxia and low pH lead to overexpression of c-myc and HMGB-1
      oncogenes in neuroblastoma cells.
AB  - PURPOSE: It has been reported that CO (2) gas, used to establish a
      pneumoperitoneum during laparoscopy, affects the behavior of tumor cells. The
      proto-oncogenes C-MYC and HMGB-1 mediate aggressive behavior of neuroblastomas.
      We studied whether exposure to CO (2), hypoxia or acidosis affects the expression
      of C-MYC and HMGB-1 in neuroblastoma cells. METHODS: SH-SY5Y cells were incubated
      with 100% CO (2), 95% helium/5% CO (2) or pH 6.2 for 2 h. The expression of C-MYC
      and HMGB-1 was measured by Western blot test immediately, 3 h and 6 h after
      incubation. Additionally, we measured apoptosis after incubation using
      fluorometric measurements of caspase 3 and 7 activity. RESULTS: C-myc (160+/-26%,
      p=0.007 and 138+/-16% vs. control, p=0.04) and HMGB-1 proteins (140+/-13% and
      136+/-11%, both p=0.037) were found to be significantly upregulated 6 h after
      incubation with CO (2) and helium. There was early upregulation of both oncogenes
      3 h after CO (2) incubation (251+/-79%, p=0.04 and 292+/-136, p=0.037).
      Correspondingly, pH 6.2 led to significant overexpression. Levels of apoptosis
      were reduced. CONCLUSIONS: Exposures mimicking conditions of CO (2)
      pneumoperitoneum lead to significant overexpression of C-MYC and HMGB-1 in
      neuroblastoma cells with decreased apoptosis. These results point to a negative
      influence and potentially increased malignancy of tumor cells.

PMID- 19387924
TI  - Outcome of transanal endorectal pull-through in patients with Hirschsprung's
      disease.
AB  - INTRODUCTION: Various outcomes following transanal endorectal pull-through
      (TERPT) in patients with Hirschsprung's disease (HD) have been reported. In this
      study, the postoperative course and functional outcome after TERPT in 25 patients
      with HD is evaluated. METHODS: Patient records of children who underwent TERPT
      for HD between 2002 and 2007 were reviewed retrospectively. Age at surgery, sex,
      associated malformations, length of follow-up, presence of colostomy, indication
      for laparotomy, length of the aganglionic segment, result of rectal examination
      under general anaesthesia 6 weeks after surgery, necessity of a dilatation
      program or reoperation were investigated. In addition, standardised interviews
      were performed to collect the following data: bowel movement per day, faecal
      continence in potty-trained children or in patients older than 3 years, incidence
      of diarrhoea or problems with micturition and the necessity for laxative therapy.
      RESULTS: Between 2002 and 2007, 25 patients underwent TERPT for HD. Median age at
      the time of surgery was 3.5 months. Median follow-up was 35 months. Calibration
      of the anus showed a normal age-related diameter of the anus in 12/20 children
      and a markedly reduced diameter in 8/20 children at 6 weeks postoperatively.
      Seven of the latter children underwent a dilatation program. A redo pull-through
      procedure was performed in 3 patients due to stenosis at the colo-anal
      anastomosis (n=1), a constricting muscle cuff (n=1) and a twisted pull-through
      (n=1). Two children developed enterocolitis. The median frequency of bowel
      movements was 3/day (1-5/day). Laxative treatment was required in only one
      patient (4.5%). None of the patients had diarrhoea. Nineteen children (86%) were
      potty-trained, being older than 3 years. Eighteen of them were continent (95%).
      One patient (5%) with trisomy 21 suffered from intermittent non-retentive faecal
      incontinence. None of the patients showed signs of neurogenic bladder
      dysfunction. CONCLUSION: The functional outcome in most patients after TERPT is
      satisfactory. We suggest that routine rectal digital examination and anal
      calibration under anaesthesia 6 weeks postoperatively might detect occult
      anodermal stenosis and allow early initiation of an anorectal dilatation program,
      which could decrease the incidence of enterocolitis, persistent constipation and
      the necessity for further surgical intervention.

PMID- 19387925
TI  - Effect of penile tourniquet on growth factors in rat penile tissue.
AB  - AIM: This study aimed to evaluate the effect of penile tourniquet application on
      growth factors in rat penile tissues. MATERIALS AND METHODS: Forty Wistar male
      rats were included in the study. Rats were divided into 4 groups. After
      anesthetization, perimeatal penile skin and the corpus cavernosum were sampled in
      the control group (CG). A Mathieu-like flap was designed without a penile
      tourniquet (PT) to serve as a sham group (SG). In the PT groups, a Mathieu-like
      flap was created and a 5 mm diameter rubber circular band was applied at the base
      of the penis. The PT was applied for 10 min in the PT-10 group and for 30 min in
      the PT-30 group. Penile tissue was sampled 24 h after PT application in the SG
      and PT groups. Tissues obtained were examined in three sections: the
      subepithelial vascular plexus (SVP), the corpus cavernosum (CC) and the smooth
      muscle-like mesenchymal cells in the corpus cavernosum (MC). Acute inflammation
      was evaluated with hematoxylin-eosin staining. The effect of PT on vascular
      endothelial growth factor (VEGF), VEGF receptor (VEGFR) and transforming growth
      factor beta receptor (TGF beta-R) levels was evaluated. RESULTS: Higher grades of
      acute inflammation were encountered in the PT-10 and PT-30 groups compared to the
      CG and SG (p<0.005). However, mean grades of acute inflammation did not show a
      statistical difference between the PT-10 and PT-30 groups (p>0.05). When the
      levels of growth factors were compared between the CG and PT-10 group, the PT-10
      group showed increased levels of VEGF and TGF beta-R. In the PT-30 group, both
      VEGF and VEGFR levels were found to be decreased. When acute inflammation grades
      of tissues were correlated with VEGF and TGF beta-R, higher acute inflammation
      grades correlated with decreased VEGF and increased TGF beta-R levels (Spearman's
      correlation, p<0.005). Although alterations in VEGF and TGF beta-R levels were
      detected in the SVP and CC of penile tissues, altered VEGFR levels were only
      detected in the MC sections. CONCLUSION: PT caused higher grades of acute
      inflammation which correlated with decreased VEGF levels and increased TGF beta-R
      levels. Decreased VEGF levels after PT may alter the angiogenesis phase of wound
      healing and cause poor angiogenesis in penile skin flaps. Increased levels of TGF
      beta-R can be considered as an acute inflammatory response to PT. These results
      confirmed that prolonged PT application may result in altered growth factors in
      penile tissue and may reduce the success rate of repair.

PMID- 19387926
TI  - Elevated serum bone morphogenetic protein 7 levels and clinical outcome in
      children with biliary atresia.
AB  - BACKGROUND AND AIM: Biliary atresia (BA) is one of the most serious liver
      disorders in children. The purposes of the present study were to investigate
      serum levels of bone morphogenetic protein 7 (BMP7) in BA children compared with
      healthy controls and to evaluate the association between serum BMP7 and the
      clinical outcome of BA patients post Kasai operation. METHODS: Sixty-two BA
      patients post Kasai operation and 14 healthy controls were enrolled. The patients
      were divided into two groups according to their serum total bilirubin levels
      (TB<2, no jaundice vs. TB> or =2 mg/dL, persistent jaundice) and alanine
      aminotransferase levels (ALT<45, normal ALT vs. ALT> or =45 IU/L, elevated ALT).
      Serum BMP7 levels were determined by commercial enzyme-linked immunoabsorbent
      assay. RESULTS: The mean serum BMP7 was higher in BA patients compared with that
      of healthy controls (35.4+/-3.6 vs. 20.6+/-2.7 pg/mL, p=0.002). The BA patients
      with persistent jaundice had more elevated serum BMP7 levels than those without
      jaundice (59.5+/-6.5 vs. 20.3+/-1.6 pg/mL, p=0.001). There was also a correlation
      between serum total bilirubin and serum BMP7 levels (r=0.57, p<0.001). Moreover,
      the levels of serum BMP7 in BA patients with elevated ALT were significantly
      higher than those with normal ALT (41.6+/-4.7 vs. 22.4+/-4.2 pg/mL, p=0.003).
      Additionally, BA patients with portal hypertension had higher increased serum
      BMP7 levels compared to those without portal hypertension (45.3+/-4.9 vs. 18.7+/
      2.8 pg/mL, p<0.001). CONCLUSION: The significant increment of serum BMP7 was
      associated with a deterioration of hepatic function and the progression of liver
      fibrosis. Serum BMP7 could be used as a prognostic marker to reflect disease
      severity and monitor disease progression in BA patients post Kasai operation.

PMID- 19387927
TI  - Non-surgical management of idiopathic fibrosing pancreatitis.

PMID- 19387928
TI  - Covered bladder exstrophy with scrotal duplication.

PMID- 19387929
TI  - [Lead pollution of drinking water in lower Saxony from corrosion of pipe
      materials].
AB  - BACKGROUND: The corrosion of drinking water pipe materials can release different
      elements into tap water. Especially important in this context is the heavy metal
      lead, which mainly leaches from the peripheral water distribution system. Lead is
      known to have numerous adverse effects especially to infants and children. AIM
      AND METHOD: The aim of this project was to assess the present state of drinking
      water contamination with lead in Lower Saxony and to promote the replacement of
      lead pipes. For this purpose a project was initiated comprising three parts.
      Firstly, a free examination of drinking water was offered in cooperation with
      local public health departments for private households with young women and
      families with children living in buildings constructed before 1974. Participants
      were asked to collect a cold tap water sample in their household after nocturnal
      stagnation and to complete a questionnaire. The collected samples were analysed
      by atomic absorption spectrometry for their lead concentration. Secondly, data
      from local public health departments on results of lead measurements, especially
      in buildings for the public, were collected and analysed. Finally, a working
      group 'lead replacement' consisting of representatives of all relevant parties
      (e.g., tenant and landlord associations, handicraft, building and health
      administration) was initiated. RESULTS: In the project in total 2,901 tap water
      samples from households were collected between the years 2005 and 2007. Of these,
      7.5% had lead concentrations exceeding 10 microg/L (recommended limit of the
      World Health Organisation) and 3.3% had concentrations above the limit of the
      German drinking water ordinance (25 microg/L). There were remarkable regional
      differences in the frequency of tap water contamination. Multi-family houses were
      more frequently affected than single and double family houses. Additional data
      were collected in a preceding study in southern Lower Saxony. Of the 1 434
      stagnation samples, 3.1% had lead concentrations greater than 10 microg/L and
      0.6% had concentrations above the former limit of the German drinking water
      regulations of 40 microg/L.

PMID- 19387930
TI  - [Psychosocial issues in outpatient care of acne vulgaris].
AB  - OBJECTIVE: This survey aims to identify psychosocial issues in the outpatient
      care of acne vulgaris in dermatological and paediatric practices. The main object
      of the study lies on the impact of psychosocial stresses and strains, and offers
      of support in medical care. METHOD: Questionnaires were sent out to all
      dermatologists and paediatricians in private practice in Westphalia-Lippe (n=678)
      using a combined quantitative and qualitative approach. The average response rate
      was 41.0% (n=278), for paediatrics 43.7% (n=190) and dermatology 36.3% (n=88),
      respectively. Methods of descriptive statistics were applied. Qualitative data
      were analysed using a qualitative content analysis. RESULTS: From the physicians'
      point of view several needs of psychosocial care are seen, however, predominantly
      focussing on psychotherapeutic and inpatient medical care. Correspondingly,
      patients' demands for psychosocial care were also indicated. The responding
      physicians were not aware of low threshold offers of support such as self-help,
      support and advocacy organisations, social services or help-desks. These offers
      do not play an important role in outpatient care. Altogether only a minor group
      of respondents cooperates with these named institutions providing psychosocial
      care services. CONCLUSIONS: The integration of psychosocial care is not common
      practice in the outpatient care of acne vulgaris. On the one hand physicians are
      willing to cooperate with caring institutions inside and outside the health care
      system; on the other hand cooperation is limited by lots of structural and fiscal
      barriers. The mental and psychological stresses related to acne vulgaris are
      evident and important for social and emotional development of children and
      adolescents. Although this fact is actually being perceived, the implementation
      of psychosocial issues is medical practice remains inadequate.

PMID- 19387931
TI  - [Planning and controlling care services for elderly migrants--an analysis of
      health-care reporting in nursing homes and at home].
AB  - Elderly migrants are a rapidly growing group in Germany. Well-grounded health and
      nursing care reports which deal with the situation of migrants are therefore
      necessary to secure an appropriate local and national planning of care for
      elderly migrants. Also quality control and development need substantiated data in
      order to ensure proper nursing care services for this segment of the population.
      This contribution explores whether and to what extent data sources provide
      information about access, quality and use of care services by migrants. The
      result: the major data sources for regional and national care planning and
      quality control render no specific information about migrants. This is
      problematic since several studies indicate severe deficits in nursing care
      services for this group.

PMID- 19387932
TI  - [The role of next of kin in medical decision-making--empirical findings from
      haemato-oncological diseases].
AB  - AIM OF THE STUDY: Models of shared decision making in the patient-doctor
      relationship are attracting increasing attention. A recent study focuses on the
      so far inadequate attention paid to the role of next of kin. It was examined in
      which decision areas next of kin of haematological cancer patients were included,
      further what support next of kin could provided and finally which factors
      encouraged the participation of next of kin in that process. METHODS: From 2006
      2008 empirical data were collected from hemato-oncological patients undergoing
      treatment as well as from their families. The participating family members of
      patients were mailed questionnaires based on the patient sample (designation of a
      family member by the patient: 118/177 or 66.7%) on average half of a year
      following the patient's (in- or outpatient) treatment. The response rate of the
      participants was 67.8% (80/118). Of the respondents, 65% were spouses or partners
      of the patients, the average age was 53.9 years, and 66.3% were female. RESULTS:
      Family members think it makes sense for them to take an active part in medical
      decisions affecting their loved ones and a majority of them reported having
      participated in decision-making processes concerning a variety of issues. Being
      involved in their loved one's discussions with their doctors has a significant
      influence on this. Family members' level of education was the only clear
      predictor for participation in discussions with doctors that could be isolated.
      CONCLUSION: It is clear that family members, especially spouses and partners,
      consider it meaningful to participate in medical decisions affecting their loved
      ones, and that they want to be able to do this in the clinical context. One
      limitation that must be mentioned is that due to the small size of the sample and
      an approach that focused on initial exploration, the results should be
      interpreted as a point of orientation. Further studies should look in more detail
      at how inner family structures play a role in patient-doctor shared decision
      making, as well as the concrete conditions and implications that play a role in
      family members' participation in this process, i.e., adherence to "doctor's
      orders" and possible decision-making conflicts on the part of the patient.

PMID- 19387933
TI  - [Garbage in - garbage out? Validity of coded diagnoses from GP claims records].
AB  - CONTEXT: ICD-10-coded diagnoses from claims records are frequently used as
      morbidity indicators for research as well as for risk adjustment purposes in
      quality management and remuneration. A requirement for this application is the
      high validity of the diagnoses. In GP practices in particular, it is questionable
      whether claims-based diagnoses realistically reflect the health problems of
      patients treated over a one year period. METHODS: In a retrospective cross
      sectional study of a random sample of 250 patients from 10 GP practices we
      examined whether, on the basis of the patients' medical records, health problems
      treated in the year 2003 matched claims-based diagnoses within the same time
      period. RESULTS: In spite of a high mean of 6.1 claims-based diagnoses per
      patient, health problems treated within the study period were under-reported in
      30% of the cases, mainly relating to non-severe diagnoses frequently encountered
      in GP practice, chronic conditions not requiring medication, and diagnoses
      justifying a screening test. An over-reporting for diseases not treated within
      the study period was observed in 19% of the cases, most often in the case of
      permanent chronic conditions. In 11% of cases the ICD-10 codes of claims-based
      diagnoses and the diagnoses in the medical records did not match ("erroneous
      codes"). For six of the diagnoses most common in GP practice (hypertension,
      diabetes, hyperlipoproteinemia, cardiovascular disease, back pain, and acute
      respiratory tract infections) correctness at 71-93% was higher than completeness
      (56-86%). CONCLUSION: The low validity of ICD-10-coded diagnoses from GP claims
      records calls their usefulness as morbidity indicators into question.

PMID- 19387934
TI  - [Vacuum therapy of an esophageal anastomotic leakage--a case report].
AB  - BACKGROUND: Esophageal anastomotic leakage is a major complication. In rectal
      surgery, anastomotic dehiscence is successfully treated by endoscopically placed
      intracavitary vacuum sponge systems. We used this technique in a case of
      anastomotic dehiscence following transhiatal gastrectomy. PATIENT AND METHOD: In
      an 80-year-old female patient esophageal anastomotic leakage was diagnosed
      endoscopically six days following transhiatal gastrectomy. Endocavitary treatment
      by endoscopic implantation of a vacuum sponge system was performed. After 14 days
      of treatment with 4 system changes and a change interval of 2-4 days complete
      healing was observed. A week later, a second wall defect was diagnosed and
      treated in the same way. The total hospital stay after operation was sixty days.
      CONCLUSION: Esophageal anastomotic leakage can be successfully treated by means
      of an endoscopically placed intracavitary vacuum sponge system. This paper
      describes the therapeutic technique.

PMID- 19387935
TI  - [Prison doctors: medicine in the midst of addiction problems and infectious
      diseases].

PMID- 19387951
TI  - [Living with limitations: people afflicted with heart failure - A qualitative
      study].
AB  - About two million people in Germany live with heart failure. However, health care
      provision is still inadequate. In order to develop patient-centred care it is
      necessary to focus on the everyday life and experiences of people with heart
      failure. Based on these insights the need for information and counselling can be
      identified and nursing interventions can be designed according to these needs.
      Within a literature analysis five international but no German studies. The focus
      lay on everyday experiences of people suffering from heart failure. The following
      research question was developed: How do people with heart failure experience
      their lives? Using the Grounded Theory approach, nine interviews and a self
      report were analysed according to Corbin and Strauss' coding paradigm. The
      central phenomenon found is the experience of limitations. To deal with these
      limitations in everyday life, patients develop two different strategies:
      ignorance or acceptance. Either they ignore the limitations in order to maintain
      their former life or they create a new normality by adopting the illness and its
      symptoms. The different strategies have special impacts on the person's roles,
      their emotions their everyday lives, and their families. The results of this
      study underline existing theories of chronic illness as well as results of
      current studies. It provides an insight into the perspective of people suffering
      from heart failure in Germany. But many questions are still unanswered so that
      further research needs to be done.

PMID- 19387952
TI  - [Individual quality of life of drug addicted patients during a drug withdrawal
      programme: Self assessment on a drug withdrawal and transition unit for adults].
AB  - The aim of this study was twofold: to examine the individual quality of life of
      drug addicted patients after being admitted to a drug withdrawal programme in a
      psychiatric hospital in Switzerland, and to check whether the individual quality
      of life changes over a period of three weeks. Within three days following
      admission, thirty patients (23 men, 7 women) were interviewed, using the half
      structured instrument Schedule for the Evaluation of Individual Quality of Life:
      a Direct Weighting Procedure for Quality of Life Domains (SEIQoL-DW). Three weeks
      later, 16 patients (who were still participating in the drug withdrawal
      programme) were interviewed for a second time. The 46 interviews were analysed by
      means of qualitative content analysis according to Morse and Field (1998). In the
      30 interviews that were conducted within the first three days following hospital
      admission, 269 individual quality of life domains (QLD) were described, from
      which 37 categories of QLD could be derived, which in turn were classified into
      nine main themes. In the second round of interviews conducted after three weeks
      in hospital, the QLD categories and the main themes remained nearly identical to
      those derived from the first round. Only one new category of QLD, <<structural
      conditions>>, could be identified and was assigned to the main QLD "distress
      factors". The rankings of some QLDs changed. The median of the Global Quality of
      Life (GLQ) index of all 30 patients amounted to 48.5 out of 100 points. The
      initial value for 16 patients who were interviewed for a second time was 57.7
      while the value for the 14 drop outs amounted to 39.9. After three weeks, the
      median of the GLQ of the remaining 16 patients increased from 57.7 to 63.1.
      Compared to a healthy population, drug addicts have a lower quality of life,
      while compared to other psychiatric groups similar quality of life can be
      observed. The SEIQoL-DW method was well accepted among patients without
      distressing them. This study shows that the quality of life of drug addicts is
      individual, multi-dimensional, dynamic and complex.

PMID- 19387953
TI  - [Relevance and modification of autonomy and care at the end of life. Results of a
      survey by means of a vignette-study].
AB  - For several years the public and the associations of nurses and physicians have
      discussed ways and possibilities for a good and professional end-of-life
      attendance of patients. In this connection a descriptive vignette-study (n = 152)
      investigates the relevancy of nurses' and physicians' capability to ensure the
      patient's autonomy (expressed by a living will) and care for the patient. In
      their vignette-stories' assessments and answers to additional questions nurses
      and physicians judge that both values, autonomy and care, are essential. But it
      remains unclear, what autonomy and care mean to them and how both values be
      joined together and modified in a practicable way. If this ambiguousness is an
      expression of the matter itself, if it therefore never becomes quite clear what
      autonomy and care mean in end-of-life attendance, legislation and professional
      curricula should take this into consideration.

PMID- 19387954
TI  - [Formal and informal tasks of community psychiatric nursing: A meta-synthesis].
AB  - Current psychiatric care relies increasingly on community mental health nursing.
      However, in German speaking countries there is a lack of education and training
      material for community psychiatric nurse. A meta-synthesis was conducted to
      identify central components of the tasks in this field from the nurses'
      perspective. We found 12 original articles which fulfilled the inclusion criteria
      (qualitative studies with samples of community mental health nurses). Formal
      tasks such as the health status assessment and the patient's medication
      management were identified as well as informal nursing issues such as the
      therapeutic relation. Community mental health nursing is on one hand
      characterised by a humane and therapeutic relation and on the other hand by
      surveillance tasks. It is concluded that training and education curricula of
      community psychiatric nurses must include formal tasks as well as informal issues
      and problems within the field.

PMID- 19387955
TI  - Varying prognostic significance of "ischemic ST depression" during vasodilator
      stress testing in patients with normal SPECT/PET myocardial perfusion imaging.

PMID- 19387956
TI  - The central nervous system and sudden cardiac death: what should we know?
AB  - The role of the central nervous system in the modulation and precipitation of
      sudden cardiac death has been a matter of controversy for decades. Establishing a
      cause-effect relationship in the setting of a cerebro-vascular event has been
      complex, as patients with stroke usually have risk factors for coronary artery
      disease as well. This article will review both experimental and clinical evidence
      relating to the mechanisms that link the central nervous system and the
      cardiovascular system. Cardiovascular consequences of stroke and epilepsy will be
      also reviewed.

PMID- 19387957
TI  - Catheter ablation of atrial fibrillation in the elderly: where do we stand?
AB  - Catheter ablation has emerged as an important therapy for the management of drug
      refractory symptomatic paroxysmal and persistent atrial fibrillation (AF).
      Although the elderly account for the majority of patients with AF, limited data
      exists regarding the use of catheter ablation for elderly patients with AF. As AF
      ablation has become more widespread, ablation techniques have improved and the
      complication rate has decreased. As a result, referrals of elderly patients for
      catheter ablation of AF are on the rise. Two retrospective analyses have recently
      demonstrated that catheter ablation of AF in the elderly can safely be performed
      and results are comparable to a younger population with up to 80% or more of
      patients maintaining sinus rhythm at 12 months follow-up. We compared the results
      of 15 consecutive patients > or = 70 years old with symptomatic paroxysmal atrial
      fibrillation who underwent catheter ablation of AF at our institution to 45
      randomly sampled younger patients. The primary endpoint of our study, presence of
      sinus rhythm in the absence of symptoms at 12 months follow-up, was present in
      60% of elderly patients and 80% of younger patients (p = 0.17). There was no
      statistically significant difference in complication rate between the younger and
      elderly patients. In this article we present the results of our study and review
      the published literature to date regarding the clinical efficacy and safety of
      catheter ablation for AF in elderly patients with paroxysmal and persistent
      atrial fibrillation.

PMID- 19387958
TI  - Adenosine-induced ST segment depression with normal perfusion.
AB  - BACKGROUND: Intravenous adenosine in conjunction with myocardial perfusion
      imaging is commonly used for the detection of coronary artery disease and risk
      assessment. We have previously shown that patients with ischemic changes on the
      12-lead electrocardiogram (ECG) in response to adenosine but with normal
      perfusion pattern have a benign outcome on short intermediate follow-up. The long
      term outcome of these patients is unknown. METHODS: Patients with ischemic ECG
      response (> or = 1 mm ST depression) to adenosine infusion but with normal
      perfusion on single-photon emission computed tomography (SPECT) imaging in the
      absence of a history of myocardial infarction or coronary revascularization were
      followed up for mortality, myocardial infarctions, and coronary
      revascularization. RESULTS: The cohort consisted of 73 patients (81% women) who
      were followed up for mortality for a mean of 61 +/- 15 months. There were 10
      deaths, and the cause of death was determined to be non-cardiac in half of those.
      Follow-up for the other endpoints was complete for 21 +/- 10 months during which
      no patient had myocardial infarction and seven underwent coronary
      revascularization. CONCLUSIONS: Patients with ischemic ECG response to
      intravenous adenosine administration and normal perfusion on SPECT are at low
      risk of cardiovascular events. The ST segment response to adenosine in this
      setting is likely related to non-ischemic mechanisms.

PMID- 19387959
TI  - The effect of left ventricular dysfunction on right ventricle ejection fraction
      during exercise in heart failure patients: Implications in functional capacity
      and blood pressure response.
AB  - BACKGROUND: The aim of this study was to assess the effect of left ventricular
      dysfunction on right ventricular ejection fraction during exercise in heart
      failure patients and its implications in functional capacity and blood pressure
      response. METHODS: In a cross-sectional study 65 patients with heart failure were
      included. Left and right ventricular ejection fractions were evaluated by radio
      isotopic ventriculography. All subjects underwent an exercise treadmill test
      (Bruce modified protocol). Systolic and diastolic blood pressures were also
      recorded. RESULTS: From the total population, 38 (58.46%) showed a significant
      increase (> or = 5%) in left ventricular ejection fraction (LVEF) and 27 (41.5%)
      showed a significant decrease in LVEF (> or = 5%) after the stress test. Patients
      with a significant reduction in LVEF during stress had lower exercise tolerance
      (4.1 +/- 2.5 vs. 6.1 +/- 2.5 METs, p = 0.009) compared to those who showed an
      increase in LVEF. Diastolic blood pressure was higher at rest among those who had
      a reduced LVEF during stress (83 +/- 12.2 vs. 72.6 +/- 12.2 mm Hg, p = 0.035) and
      during exercise (95 +/- 31.3 vs. 76.9 +/- 31.3 mm Hg, p = 0.057), as well as mean
      arterial pressure in the same group (97.1 +/- 11.6 mm Hg, p = 0.05). In addition,
      this group decrease of -8.8 +/- 51.6% in the right ventricular ejection fraction
      after exercise compared to an increase of 27.3 +/- +/- 49.1% (p = 0.007) among
      the patients with an increase in LVEF. CONCLUSIONS: Biventricular systolic
      dysfunction during exercise is associated with higher rest and stress blood
      pressure and worse functional capacity.

PMID- 19387960
TI  - Evaluation of exercise capacity with cardiopulmonary exercise test and B-type
      natriuretic peptide in adults with congenital heart disease.
AB  - BACKGROUND: Adult patients with congenital heart disease (CHD) usually find their
      exercise capacity satisfactory. However, objective evaluation is important for
      diagnostic and prognostic purposes. The aim of this study was to evaluate
      exercise capacity using cardiopulmonary exercise tests and measurement of serum B
      type natriuretic peptide (BNP) levels in adult patients with CHDs, both in the
      entire study cohort and in subjects with individual types of cardiac lesions, as
      well as to verify the relation between BNP level and cardiac performance.
      METHODS: The study group included 265 patients (136 males; mean age 34.4 +/- 11.6
      years) 173 of whom were operated on at the mean age of 9.2 +/- 7.3 years. They
      represented the following types of CHD: 72 patients--surgically corrected
      coarctation of the aorta, 62--surgically corrected tetralogy of Fallot, 28-
      Ebstein anomaly, 26--patent atrial septal defect, 24--Eisenmenger syndrome, 20-
      uncorrected or palliated complex cyanotic lesions, 11--corrected transposition of
      the great arteries (TGA), 14--TGA after Senning operation, and 8--common
      ventricle after Fontana operation. The control group consisted of 39 healthy
      individuals (17 males) with a mean age of 35.8 +/- 9.3 years. RESULTS: According
      to NYHA classification, 207 patients were recognized as representing class I
      symptoms, 47 subjects class II, and 11 class III. Cardiopulmonary exercise
      revealed significantly reduced exercise capacity in adults with CHD in general,
      compared to control subjects: maximal oxygen uptake (VO2max) was 23.3 +/- 6.9 vs.
      33.6 +/- 7.2 mL/kg/min, respectively (p = 0.00001); maximum heart rate at peak
      exercise (HRmax) -161.1 +/- 33.2 vs. 179.6 +/- 12.3 bpm (p = 0.00001);
      respiratory workload (VE/VCO2slope) - 35.7 +/- 9.7 vs. 26.3 +/- 3.1 (p =
      0.00001); and forced vital capacity (FVC) - 3.8 +/- 1.1 vs. 4.6 +/- 0.7 L (p =
      0.00003). Various degrees of peak VO2max reduction were observed across the
      spectrum of CHD. Patients after repair of aortic coarctation demonstrated the
      highest VO2max (26.8 +/- 6.6 mL/kg/min), and the lowest was demonstrated by
      patients with Eisenmenger syndrome (12.8 +/- 4.8; ANOVA p = 0.00001). Serum BNP
      levels in the study group were higher than in the controls: 55.4 +/- 67.5 vs.
      13.9 +/- 13.7 pg/mL, respectively (p = 0.00001). Various degrees of BNP level
      increase were found across the spectrum of CHD. Patients after repair of aortic
      coarctation demonstrated the lowest BNP level (24.8 pg/mL), and the highest level
      was found in patients with cyanotic defects (120.7 pg/mL; ANOVA p = 0.00001). BNP
      levels across the NYHA classes were as follows: I--35.7 pg/mL, II--94.1 pg/mL,
      and III--225.6 pg/mL. BNP levels showed negative correlation with VO2max (r = 
      0.525, p = 0.0001), FVC (r = -0.349, p = 0.00001), FEV1 (r = -0.335, p =
      0.00001), and positive correlation with VE/VCO2slope (r = 0.447, p = 0.00001).
      CONCLUSIONS: The exercise capacity of patients with CHD is, in general,
      compromised, most strikingly in patients suffering from pulmonary hypertension
      and cyanosis. Serum BNP levels in these subjects are increased and correlate well
      with exercise capacity. BNP level is higher in patients with cyanotic CHDs.

PMID- 19387961
TI  - Microalbuminuria correlates with the prevalence and severity of coronary artery
      disease in non-diabetic patients.
AB  - BACKGROUND: It has been shown that microalbuminuria is an independent risk factor
      for cardiovascular diseases in diabetics, hypertensive patients and in the
      general population. However, few data has addressed the correlation of
      microalbuminuria with the severity of coronary artery disease (CAD). The aim of
      the study was to assess the association of microalbuminuria with the prevalence
      and severity of CAD. METHODS: The subjects, 79 men and 74 women aged 45-70 years,
      were classified as CAD-negative and CAD-positive according to the results of
      coronary angiography. The severity of CAD was scored on the basis of the number
      and the extent of lesions within the coronary arteries. Urine albumin excretion
      was measured in 24 h urine samples by method of nephelometry. RESULTS: Coronary
      artery disease occurred more frequently in males than in females and in smokers
      than in non-smokers. There were no significant differences in the prevalence of
      hypertension and hypercholesterolemia between two groups. Microalbuminuria was
      more prevalent in CAD-positive patients than in controls (62.9% vs. 8.8%; p < or
      = 0.001). Patients with microalbuminuria compared with the controls had increased
      prevalence of one (15.3% vs. 7.4%, p pound 0.001), two (50% vs. 22.2%, p < or =
      0.001), and three vessel disease (29.2% vs. 19.8%, p < or = 0.001).
      Microalbuminuria exhibited a significant correlation with the severity of CAD (r
      = 0.40; p < or = 0.001). CONCLUSIONS: Patients with microalbuminuria have more
      severe angiographically detected CAD than those without microalbuminuria. The
      results indicate that microalbuminuria exhibits a significant association with
      the presence and severity of CAD.

PMID- 19387962
TI  - Correlation between endothelial dysfunction in normal coronary patients with slow
      flow and aortic ectasia: the first report.
AB  - BACKGROUND: Slow coronary flow (SCF) is slow dye progression in the coronary
      arteries during selective angiography, but there is no such study about greater
      visceral vessels. Studies have suggested that flow-mediated dilation (FMD) is
      impaired in SCF. Endothelial function can be assessed by FMD in the brachial
      artery as ischemia-induced vasodilation. Since inflammation is an underlying
      pathology in the inflammation of visceral vessels and probably SCF, we studied
      the correlation of aortic ectasia and SCF by means of FMD. METHODS: Patients with
      normal coronary arteries and SCF formed the case group, and patients with normal
      coronary arteries and normal coronary flow formed the control group. We measured
      the diameter of the patients' brachial artery at rest, after inflation of a
      sphygmomanometer on the forearm [endothelial-dependent vasodilation (EDV)], and
      after use of sublingual nitrate (endothelial-independent vasodilation) by
      sonography. We also measured the diameter of the aorta using sonography before
      administration of sublingual nitrate. Endothelial dysfunction was defined as EDV
      significantly less than standard EDV. RESULTS: There were insignificant
      differences between age, gender, and frequency of cardiac risk factors within the
      case and control groups, but diabetes mellitus was significantly different
      between the two groups. The diameter of the aorta was insignificantly different
      between the case and control groups. The response of the brachial artery to the
      cuff test and sublingual nitrate were insignificantly different between the case
      and control groups. Endothelial dysfunction based on cuff test and sublingual
      nitrate administration was significantly more common in men than women, as the p
      values for cuff and sublingual nitrate were 0.033 and 0.051, respectively.
      CONCLUSIONS: It seems that there is no correlation between SCFP and aortic
      ectasia.

PMID- 19387963
TI  - Clinical significance of mitral leaflet flail.
AB  - BACKGROUND: There has been scant academic consideration paid to investigations of
      mitral leaflet flail in terms of clinical profile, surgical strategy, and
      surgical outcome. METHODS: One hundred consecutive patients with mitral leaflet
      flail referred for surgical treatment in the past 4(2/3) years were included in
      this study. RESULTS: The most common reasons leading to mitral leaflet flail were
      chord rupture (38%), myxomatous degeneration (23%), and combined chord rupture
      and myxomatous degeneration (12%). Mitral leaflet flail was predominantly
      characterized by independent P(2) flail, followed by P(2,3) flail and independent
      A(2) flail. Chord rupture occurred in 54 patients, and the most commonly involved
      segments were P(2), P(2,3), and P(3). The most common risk factors for mitral
      valve replacement were papillary muscle rupture, extensive myxomatous
      degeneration, extensive chord rupture, and severely dilated mitral valve annulus.
      Multivariate regression analyses demonstrated that the development of mitral
      leaflet flail was significantly associated with the pertinent variables tested,
      especially correlated with insertion of the prosthetic ring, number of artificial
      chord, and presence of carotid stenosis. CONCLUSIONS: Mitral leaflet flail may
      affect patients of any age, but is more prevalent among males and younger
      patients. Mitral chord rupture was the leading cause for mitral leaflet flail.
      Myxomatous degeneration, infective endocarditis, mitral annulus calcification,
      and papillary muscle rupture were the next most common causes. An increased
      incidence of mitral leaflet flail was closely related to the chords of the
      posterior leaflet and the middle scallop. Due to the progressive disappointing
      prognosis of mitral leaflet flail, surgery should be performed at an early stage.

PMID- 19387964
TI  - Correlation analysis of atrial natriuretic peptide concentration,
      echocardiographic left atrial and left ventricular dimensions, and renal function
      parameters in patients after permanent pacemaker implantation.
AB  - BACKGROUND: Atrial endocrine function was established in the second half of the
      20th century, confirming the role of atrial natriuretic peptide (ANP) and brain
      natriuretic peptide (BNP) in the physiology of the cardiovascular system. The
      present study was undertaken to evaluate changes in ANP and echocardiographic
      parameters within the first month after VVI and DDD pacemaker implantation and to
      evaluate correlations between the parameters. METHODS: The study population
      consisted of group I--20 VVI patients aged 71-90 years (mean age 77.5 +/- 5.9)
      and group II--20 DDD/VDD patients aged 49-81 years (mean age 68.9 +/- 11).
      Fifteen healthy volunteers aged 58-80 years (mean age 72.7 +/- 2.8) served as
      controls. Correlations between ANP levels and cardiac cavity dimensions and
      between ANP and parameters of renal function were studied. RESULTS: Blood levels
      of ANP decreased after pacemaker implantation: in the VVI group from 168.61 +/-
      81.95 pg/1000 microL to 118.04 +/- 61.06 pg/1000 microL at 7 days and to 121.4 +/
      71.90 pg/1000 microL at 30 days; and in the DDD/VDD group from 134.89 +/- 83.11
      pg/1000 microL to 104.96 +/- +/- 57.09 pg/1000 microL at 7 days and to 110.82 +/-
      53.32 pg/1000 microL at 30 days. There was a significant correlation between ANP
      levels and left atrial size in the DDD/VDD group--0.598 (p = 0.005) and 0.593 (p
      = 0.005) and left ventricular dimensions--0.499 (p = 0.024) and 0.485 (p =
      0.030). CONCLUSIONS: ANP decreases significantly after pacing implementation in
      patients selected for implantation of VVI and DDD/VDD pacemakers. ANP correlates
      significantly with echocardiographic measurements in patients selected for
      DDD/VDD pacemakers, but no significant correlation is observed in VVI patients
      qualifying for permanent pacemaker due to atrioventricular block.

PMID- 19387965
TI  - Successful radiofrequency ablation of a right posteroseptal accessory pathway
      through an anomalous inferior vena cava and azygos continuation in a patient with
      incomplete situs inversus.
AB  - We present a 43-year-old patient with paroxysmal supraventricular tachycardia. In
      the process of catheter ablation, we found interruption of the inferior vena cava
      with azygos continuation with incomplete situs inversus. In this patient, we
      adopted the lower approach via the anomalous inferior vena cava and azygos
      continuation to achieve stability of radiofrequency catheter for right
      posteroseptal accessory pathway, and successfully abolished the preexcitation.

PMID- 19387966
TI  - Primary percutaneous coronary intervention for acute myocardial infarction in a
      patient with dextrocardia.
AB  - Dextrocardia is a rare cardiac anomaly in which the heart is located in the right
      hemithorax. This developmental irregularity can occur in isolation as situs
      solitus, or in association with situs inversus or situs ambiguous. Although there
      are reports of coronary angiography in patients with dextrocardia, there are very
      few reported cases of mechanical intervention. We report a patient with
      dextrocardia and situs inversus who presented with an ST segment elevation
      myocardial infarction and was successfully treated with primary percutaneous
      coronary intervention.

PMID- 19387967
TI  - Ciprofloxacin induced acquired long QT syndrome in a patient under class III
      antiarrhythmic therapy.
AB  - We report one case of cardiac arrest related to ciprofloxacin administration. One
      female patient (aged 70 years old) developed a marked QTc prolongation (QTc =
      0.62 s) within 24 hours of ciprofloxacin administration, with documented torsades
      de pointes and recurrent syncope that required defibrillation. The patient was
      under amiodarone and sotalol therapy for atrial fibrillation, with no obvious QT
      prolongation prior to ciprofloxacin therapy. QT prolongation and subsequent
      torsades de pointes appeared only after initiation of ciprofloxacin and
      normalized after drug discontinuation. Even though ciprofloxacin is thought to be
      safer than other agents in its class, it may cause QT prolongation and torsades
      de pointes, particularly in high risk patients with predisposing factors.
      Prolongation of the QT interval related to the effect of fluoroquinolones on
      rapid potassium channels (IKr) may result on potentially serious proarrhythmic
      effect, leading to torsades de pointes.

PMID- 19387968
TI  - Misdiagnosed right atrial tumor identified by intraoperative transesophageal
      echocardiography.

PMID- 19387969
TI  - Magnetic guidance for cardiac procedures.

PMID- 19387970
TI  - Dual antiplatelet therapy and antithrombotic treatment: Recommendations and
      controversies.
AB  - Dual antiplatelet therapy is currently recommended for all patients with acute
      coronary syndromes, independent of whether they receive pharmacological treatment
      or undergo percutaneous coronary intervention. Antiplatelet agents are the
      cornerstone of pharmacological treatment in interventional cardiology. However,
      there is a clear need for randomized trials to assess the treatment strategy of
      dual antiplatelet therapy in patients who also need long-term antithrombotic
      treatment (such as those with atrial fibrillation, prosthetic heart valve, mitral
      valve regurgitation or stenosis, deep vein thrombosis, pulmonary embolism, or
      pulmonary hypertension). In this paper we discuss trials and analyses on the use
      of dual antiplatelet treatment in combination with antithrombotic therapy in
      particular diseases, with a focus on the risk of hemorrhagic events connected
      with this treatment, as well as recent guidelines of the European Society of
      Cardiology, the American College of Cardiology, and the American Heart
      Association.

PMID- 19387971
TI  - Naum Lazarevich Gurvich (1905-1981) and his contribution to the history of
      defibrillation.

PMID- 19387972
TI  - Videotaped interrogations and confessions: does a dual-camera approach yield
      unbiased and accurate evaluations?
AB  - Although an equal-focus camera perspective-suspect and interrogator each
      displayed in profile-produces relatively unbiased assessments of videotaped
      interrogations-confessions, many in law enforcement may consider it less than
      satisfactory because a full-face view of the suspect is precluded and thus
      potentially important information revealed in his or her expressions may be
      unavailable for fact finders' consideration. The present research investigated
      whether a dual-camera approach, wherein the full faces of both the suspect and
      interrogator are presented in a split-screen format simultaneously, is a viable
      alternative to an equal-focus format. Experiment 1 in fact demonstrated that the
      dual-camera approach does produce relatively unbiased assessments of
      voluntariness and guilt. However, Experiment 2 revealed that the dual-camera
      approach was one of the poorest presentation formats in terms of its impact on
      the ability to accurately distinguish between true and false confessions. Policy
      recommendations based on the present and previous research are presented.

PMID- 19387973
TI  - Atan1p-an extracellular tannase from the dimorphic yeast Arxula adeninivorans:
      molecular cloning of the ATAN1 gene and characterization of the recombinant
      enzyme.
AB  - The tannase-encoding Arxula adeninivorans gene ATAN1 was isolated from genomic
      DNA by PCR, using as primers oligonucleotide sequences derived from peptides
      obtained after tryptic digestion of the purified tannase protein. The gene
      harbours an ORF of 1764 bp, encoding a 587-amino acid protein, preceded by an N
      terminal secretion sequence comprising 28 residues. The deduced amino acid
      sequence was similar to those of tannases from Aspergillus oryzae (50% identity),
      A. niger (48%) and putative tannases from A. fumigatus (52%) and A. nidulans
      (50%). The sequence contains the consensus pentapeptide motif (-Gly-X-Ser-X-Gly-)
      which forms part of the catalytic centre of serine hydrolases. Expression of
      ATAN1 is regulated by the carbon source. Supplementation with tannic acid or
      gallic acid leads to induction of ATAN1, and accumulation of the native tannase
      enzyme in the medium. The enzymes recovered from both wild-type and recombinant
      strains were essentially indistinguishable. A molecular mass of approximately 320
      kDa was determined, indicating that the native, glycosylated tannase consists of
      four identical subunits. The enzyme has a temperature optimum at 35-40 degrees C
      and a pH optimum at approximately 6.0. The enzyme is able to remove gallic acid
      from both condensed and hydrolysable tannins. The wild-type strain LS3 secreted
      amounts of tannase equivalent to 100 U/l under inducing conditions, while the
      transformant strain, which overexpresses the ATAN1 gene from the strong,
      constitutively active A. adeninivorans TEF1 promoter, produced levels of up to
      400 U/l when grown in glucose medium in shake flasks.

PMID- 19387974
TI  - Total chemical synthesis of the D2 domain of human VEGF receptor 1.
AB  - The interaction of the vascular endothelial growth factor (VEGF) with its
      cellular receptors exerts a central role in the regulation of angiogenesis. Among
      these receptors, the VEGF receptor 1 may be implicated in pathological
      angiogenesis. Here, we report the first total chemical synthesis of the VEGF
      binding domain of the VEGF receptor 1. Aggregation issues were overcome by the
      use of a low-substituted resin and the stepwise introduction of pseudoproline
      dipeptides and Dmb-glycines. The folding of the protein was achieved by air
      oxidation and its biological activity was verified on ELISA-based assays.

PMID- 19387975
TI  - A model selection approach to analysis of variance and covariance.
AB  - An alternative to analysis of variance is a model selection approach where every
      partition of the treatment means into clusters with equal value is treated as a
      separate model. The null hypothesis that all treatments are equal corresponds to
      the partition with all means in a single cluster. The alternative hypothesis
      correspond to the set of all other partitions of treatment means. A model
      selection approach can also be used for a treatment by covariate interaction,
      where the null hypothesis and each alternative correspond to a partition of
      treatments into clusters with equal covariate effects. We extend the partition-as
      model approach to simultaneous inference for both treatment main effect and
      treatment interaction with a continuous covariate with separate partitions for
      the intercepts and treatment-specific slopes. The model space is the Cartesian
      product of the intercept partition and the slope partition, and we develop five
      joint priors for this model space. In four of these priors the intercept and
      slope partition are dependent. We advise on setting priors over models, and we
      use the model to analyze an orthodontic data set that compares the frictional
      resistance created by orthodontic fixtures.

PMID- 19387976
TI  - A pharmacoscintigraphic study of three time-delayed capsule formulations in
      healthy male volunteers.
AB  - Three time-delayed capsule (TDC) formulations were investigated in a
      pharmacoscintigraphic study, using a three-way crossover design in eight healthy
      male volunteers. Additionally, the pulsed release of a TDC was investigated with
      time-lapse photography, using a nondisintegrating riboflavin tablet. The
      photographic study indicated how the release characteristics of the TDC relied on
      the erosion of a tablet containing hypromellose (HPMC). Each TDC was duel radio
      labelled with indium-111 and technetium-99 m DTPA complexes, to observe drug
      release scintigraphically (theophylline was a marker compound). Three
      formulations, having in vitro dissolution release times of 1.8, 2.9 or 4.0 h were
      shown to compare favourably with mean in vivo scintigraphic release times of 2.7,
      3.0 and 4.0 h for each formulation containing 20, 24 or 35% (w/w) HPMC
      concentrations respectively. An increase in HPMC concentration was associated
      with a delayed technetium release time, and followed the same rank order as the
      in vitro dissolution study. Observed radiolabel dispersion always occurred in the
      small intestine. In conclusion, the study established that the TDC performs and
      demonstrates an in vitro-in vivo correlation. Additionally, time and site of
      release were accurately visualized by gamma scintigraphy, and confirmed with
      determination of theophylline absorption.

PMID- 19387977
TI  - Estimation of incidences of infectious diseases based on antibody measurements.
AB  - Owing to under-ascertainment it is difficult if not impossible to determine the
      incidence of a given disease based on cases notified to routine public health
      surveillance. This is especially true for diseases that are often present in mild
      forms as for example diarrhoea caused by foodborne bacterial infections. This
      study presents a Bayesian approach for obtaining incidence estimates by use of
      measurements of serum antibodies against Salmonella from a cross-sectional study.
      By comparing these measurements with antibody measurements from a follow-up study
      of infected individuals it was possible to estimate the time since last infection
      for each individual in the cross-sectional study. These time estimates were then
      converted into incidence estimates. Information about the incidence of Salmonella
      infections in Denmark was obtained by using blood samples from 1780 persons. The
      estimated incidence was about 0.094 infections per person year. This number
      corresponds to 325 infections per culture-confirmed case captured in the Danish
      national surveillance system. We present a novel approach, termed as
      seroincidence, that has potentials to compare the sensitivity of public health
      surveillance between different populations, countries and over time.

PMID- 19387978
TI  - Selective recognition of thymidine homopolymer (poly T) oligonucleotide with
      cobalt(II)-4-[(5-chloro-2-pyridyl)azo]-1,3-diaminobenzene complex.
AB  - The interactions of cobalt(II)-4-[(5-chloro-2-pyridyl)azo]-1,3-diaminobenzene (5
      Cl-PADAB) complex with different kinds of homopolymer oligonucleotides in basic
      medium were investigated based on the measurements of resonance light scattering,
      UV-vis, circular dichroism spectra and dark field light-scattering imaging.
      Experiments showed that only thymidine homopolymer (poly T) oligonucleotides with
      the length in the range of poly T6 to poly T18 could interact with the Co(II)-5
      Cl-PADAB complex in alkaline conditions and cause evident color and spectral
      change. Thus, the binary complex of Co(II)-5-Cl-PADAB could be employed as a
      visual probe for selectively recognizing the poly T oligonucleotides.

PMID- 19387979
TI  - No gender differences in brain activation during the N-back task: an fMRI study
      in healthy individuals.
AB  - Gender differences have been well established in verbal and spatial abilities but
      few studies have examined if these differences also extend into the domain of
      working memory in terms of behavioural differences and brain activation. The
      conclusions that can be drawn from these studies are not clear cut but suggest
      that even though gender differences might not be apparent from behavioural
      measures, the underlying neural substrate associated with working memory might be
      different in men and women. Previous research suggests activation in a network of
      frontal and parietal regions during working memory tasks. This study aimed to
      investigate gender differences in patterns of brain activation during a verbal
      version of the N-back working memory task, which incorporates the effects of
      increased demands on working memory. A total of 50 healthy subjects, aged 18 to
      58 years, that were equally split by gender were recruited matched for age,
      levels of education and ethnicity. All subjects underwent functional magnetic
      resonance imaging. We found that men and women performed equally well in terms of
      accuracy and response times, while using similar brain regions to the same
      degree. Our observations indicate that verbal working memory is not affected by
      gender at the behavioural or neural level, and support the findings of a recent
      meta-analysis by Hyde ([ 2005]: Sex Roles 53:717-725) that gender differences are
      generally smaller than intra-gender differences in many cognitive domains.

PMID- 19387980
TI  - A comparison of Granger causality and coherency in fMRI-based analysis of the
      motor system.
AB  - The ability of functional MRI to acquire data from multiple brain areas has
      spurred developments not only in voxel-by-voxel analyses, but also in
      multivariate techniques critical to quantifying the interactions between brain
      areas. As the number of multivariate techniques multiplies, however, few studies
      in any modality have directly compared different connectivity measures, and fewer
      still have done so in the context of well-characterized neural systems. To focus
      specifically on the temporal dimension of interactions between brain regions, we
      compared Granger causality and coherency (Sun et al., 2004, 2005: Neuroimage
      21:647-658, Neuroimage 28:227-237) in a well-studied motor system (1) to gain
      further insight into the convergent and divergent results expected from each
      technique, and (2) to investigate the leading and lagging influences between
      motor areas as subjects performed a motor task in which they produced different
      learned series of eight button presses. We found that these analyses gave
      convergent but not identical results: both techniques, for example, suggested an
      anterior-to-posterior temporal gradient of activity from supplemental motor area
      through premotor and motor cortices to the posterior parietal cortex, but the
      techniques were differentially sensitive to the coupling strength between areas.
      We also found practical reasons that might argue for the use of one technique
      over another in different experimental situations. Ultimately, the ideal approach
      to fMRI data analysis is likely to involve a complementary combination of
      methods, possibly including both Granger causality and coherency.

PMID- 19387981
TI  - Comparison of piece-wise linear, linear, and nonlinear atlas-to-patient warping
      techniques: analysis of the labeling of subcortical nuclei for functional
      neurosurgical applications.
AB  - Digital atlases are commonly used in pre-operative planning in functional
      neurosurgical procedures performed to minimize the symptoms of Parkinson's
      disease. These atlases can be customized to fit an individual patient's anatomy
      through atlas-to-patient warping procedures. Once fitted to pre-operative
      magnetic resonance imaging (MRI) data, the customized atlas can be used to plan
      and navigate surgical procedures. Linear, piece-wise linear and nonlinear
      registration methods have been used to customize different digital atlases with
      varying accuracies. Our goal was to evaluate eight different registration methods
      for atlas-to-patient customization of a new digital atlas of the basal ganglia
      and thalamus to demonstrate the value of nonlinear registration for automated
      atlas-based subcortical target identification in functional neurosurgery. In this
      work, we evaluate the accuracy of two automated linear techniques, two piece-wise
      linear techniques (requiring the identification of manually placed anatomical
      landmarks), and four different automated nonlinear atlas-to-patient warping
      techniques (where two of the four nonlinear techniques are variants of the ANIMAL
      algorithm). Since a gold standard of the subcortical anatomy is not available,
      manual segmentations of the striatum, globus pallidus, and thalamus are used to
      derive a silver standard for evaluation. Four different metrics, including the
      kappa statistic, the mean distance between the surfaces, the maximum distance
      between surfaces, and the total structure volume are used to compare the warping
      techniques. The results show that nonlinear techniques perform statistically
      better than linear and piece-wise linear techniques. In addition, the results
      demonstrate statistically significant differences between the nonlinear
      techniques, with the ANIMAL algorithm yielding better results.

PMID- 19387987
TI  - Joining and interconnect formation of nanowires and carbon nanotubes for
      nanoelectronics and nanosystems.
AB  - Interconnect formation is critical for the assembly and integration of
      nanocomponents to enable nanoelectronics- and nanosystems-related applications.
      Recent progress on joining and interconnect formation of key nanomaterials,
      especially nanowires and carbon nanotubes, into functional circuits and/or
      prototype devices is reviewed. The nanosoldering technique through nanoscale lead
      free solders is discussed in more detail in this Review. Various strategies of
      fabricating lead-free nanosolders and the utilization of the nanosoldering
      technique to form functional solder joints are reviewed, and related challenges
      facing the nanosoldering technique are discussed. A perspective is given for
      using lead-free nanosolders and the nanosoldering technique for the construction
      of complex and/or hybrid nanoelectronics and nanosystems.

PMID- 19387988
TI  - In-wire conversion of a metal nanorod segment into an organic semiconductor.

PMID- 19387989
TI  - Enantioselective cyanoformylation of aldehydes catalyzed with solid base mediated
      chiral V(V) salen complexes.
AB  - Polymeric and monomeric V(V) chiral salen complexes-catalyzed enantioselective
      ethyl cyanoformylation of aldehydes using ethyl cyanoformate as a source of
      cyanide was accomplished in the presence of several basic cocatalysts viz., NaOH,
      KOH, basic Al2O3 and hydrotalcite. Excellent yield (>95%) of chiral ethyl
      cyanohydrincarbonate with high enantioselectivity up to 94% was achieved in 24-36
      h when hydrotalcite was used as an additive. The polymeric catalyst 1 is more
      reactive than the monomeric catalyst 2 to produce chiral ethyl
      cyanohydrincarbonate in high optical purity. The chiral polymeric catalyst 1 and
      cocatalysts hydrotalcite and basic alumina used in this study were recoverable
      and recyclable several times with retention of its performance.

PMID- 19387990
TI  - Pharmacokinetics of nateglinide enantiomers and their metabolites in Goto
      Kakizaki rats, a model for type 2 diabetes mellitus.
AB  - The pharmacokinetics of (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D
      phenylalanine (nateglinide) and its enantiomer (L-enantiomer) was studied in Goto
      Kakizaki (GK) rats after intravenous administration of nateglinide or L
      enantiomer at a dose of 40 micromol/kg body weight. Nateglinide, its L-enantiomer
      and their metabolites in serum, bile and urine were determined. The total
      clearance (CL(tot)) and the volume of distribution (Vd) was slightly higher for
      nateglinide than those for L-enantiomer in control rats, although the differences
      were not statistically significant. The cumulative excretions of L-M1 (major
      metabolite of L-enantiomer) and L-M2 (major metabolite of L-enantiomer) into bile
      were almost the same as that of M1 (major metabolite of nateglinide)and M2 (major
      metabolite of nateglinide). In GK rats, CL(tot) and Vd were higher for
      nateglinide than those for L-enantiomer. The cumulative excretion of L-M1 and L
      M2 were not different from those of M1 and M2, respectively, into bile or urine.
      CL(tot) and Vd for nateglinide or L-enantiomer in GK rats were not different from
      those in control rats. The total excretion of M1, M2, L-M1, and L-M2 into bile or
      urine in GK rats was not substantially different from that of control rats. These
      results suggest that the L-enantiomer of nateglinide shows higher CL(tot) and Vd
      compared with nateglinide, especially in the diabetic state.

PMID- 19387991
TI  - Synthesis and chiroptical properties of chiral azoaromatic dendrimers with a C3
      symmetrical core.
AB  - New chiral azoaromatic dendrimeric systems have been synthesized starting from
      1,3,5-benzenetricarbonyl trichloride as the core molecule. The simultaneous
      presence of the (S)-3-hydroxy pyrrolidinyl ring as the optically active moiety
      and the azobenzene donor-acceptor conjugated system as the photochromic group
      with permanent dipole moment, makes these systems potentially interesting as
      materials for advanced applications in nanotechnologies. All the compounds
      obtained have been characterized with particular attention to the effects induced
      by changing the electron-withdrawing group in the chromophoric moiety and to
      their optical activity. A strong nonlinear enhancement of chiroptical properties
      related to the number of chiral units linked to the symmetrical core is observed
      in these derivatives, which indicates the presence of conformationally chiral
      substructures.

PMID- 19387992
TI  - The relationship between attention deficit hyperactivity disorder, conduct
      disorder, and psychopathy in adolescent male and female detainees.
AB  - Although ADHD and CD are apparent risk factors for adult psychopathy, there are
      three distinct perspectives regarding their relationships to psychopathy: (1)
      ADHD may contribute uniquely to the development of psychopathy or (2) its
      contribution may reflect its high comorbidity with CD. Alternatively, (3) the
      comorbid presence of ADHD and CD may confer unique risk for the development of
      psychopathy. Although prior adult studies have yielded conflicting findings, no
      prior studies of adolescents address this issue. We examined these three
      hypotheses and the possibility of sex differences using cross-sectional analyses
      in 90 male and 123 female incarcerated adolescents. Among males the influence of
      ADHD was largely attributable to the overlap between ADHD and CD, whereas among
      females ADHD contributed independently to psychopathy scores and to scores on
      several dimensions of psychopathy. In addition, among females, the ADHD x CD
      interaction was significant for the total score and the antisocial component of
      psychopathy and in a direction opposite to that predicted by the comorbid subtype
      hypothesis. These findings indicate that there may be sex-specific pathways to
      elevations in psychopathic traits and suggest that the comorbid subtype
      hypothesis is probably not correct for either boys or girls.

PMID- 19387993
TI  - Embryonic stem cells derived from somatic cloned and fertilized blastocysts are
      post-transcriptionally indistinguishable: a MicroRNA and protein profile
      comparison.
AB  - Therapeutic cloning, whereby somatic cell nuclear transfer is used to generate
      customized embryonic stem cells (NT-ES) from differentiated somatic cells of
      specific individuals, has been successfully performed in mice and non-human
      primates. Safety concerns have prevented this technology from being potentially
      applied to humans, as severely abnormal phenotypes have been observed in cloned
      animals. Although it has been demonstrated that the transcriptional profiles and
      developmental potentials of ES cells derived from cloned blastocysts are
      identical to those of ES cells derived from fertilized blastocysts (F-ES), a
      systematic analysis of the post-transcriptional profiles of NT-ES cell lines has
      not yet been performed. To investigate whether NT-ES cells are comparable to F-ES
      cells post-transcriptionally, we compared the microRNA and protein profiles of
      five NT- and matching F-ES cell lines by microRNA microarray, 2-D DIGE and
      bioinformatic analyses. Stem-loop real-time PCR and MS/MS assays were further
      performed to verify the expression of specific microRNAs and characterize
      differentially expressed proteins. Our results demonstrate that the ES cell lines
      derived from cloned and fertilized mouse blastocysts have highly similar microRNA
      and protein expression profiles, consistent with their similar developmental
      potentials and transcriptional profiles.

PMID- 19387994
TI  - Effects of the CYP2D6*10 alleles and co-medication with CYP2D6-dependent drugs on
      risperidone metabolism in patients with schizophrenia.
AB  - OBJECTIVE: Risperidone is converted to 9-hydroxyrisperidone by CYP2D6. Two
      parameters were used to examine the influences of CYP2D6 polymorphism and of co
      medication on risperidone metabolism: the risperidone:9-hydroxyrisperidone
      concentration ratio (R:9-OHR ratio) and the sum of the risperidone and 9
      hydroxyrisperidone concentrations divided by the dose (C:D ratio). We evaluated
      the effect of the CYP2D6*10 allele, which is a prevalent mutant allele among East
      Asians. METHODS: Genotyping using the P450 microarray system was performed for 89
      Japanese patients with schizophrenia receiving risperidone. The patients with
      CYP2D6*1/*1, *1/*2, or *2/*2 were classified as Group 1, those with one CYP2D6*10
      allele (CYP2D6*1/*10 or *2/*10) were classified as Group 2, and those with two
      CYP2D6*10 alleles were classified as Group 3. The R:9-OHR and C:D ratios were
      analyzed using two-way ANOVAs with the CYP2D6 genotype and co-medication with
      CYP2D6-dependent drugs as independent variables. RESULTS: Both the "genotype" and
      the "co-medication" factors had significant impacts on the R:9-OHR ratio (p =
      0.011, p < 0.001). The "genotype" factor also had a significant impact on the C:D
      ratio (p = 0.032). However, the "co-medication" factor did not have a significant
      impact on the C:D ratio (p = 0.129). CONCLUSIONS: The CYP2D6*10 polymorphism and
      the presence of co-medication exerted significant influences on the
      pharmacokinetics of risperidone.

PMID- 19387996
TI  - Remodeling pharmaceutical care in Sub-Saharan Africa (SSA) amidst human resources
      challenges and the HIV/AIDS pandemic.
AB  - Pharmaceutical care, meant to complement a proper drug supply system, is a key
      component of a robust health care system and is the direct, responsible provision
      of medication-related care designed to achieve definite outcomes that improve a
      patient's quality of life. Beyond simply dispensing medicine, pharmaceutical care
      promotes adherence to therapeutic regimens and addresses problems such as
      overdosage, sub-therapeutic dosage, adverse drug reactions, medication errors,
      and untreated indications. The dearth of health care workers trained in
      pharmaceutical care coupled with inadequate access to medications creates
      multiple disease management challenges in Sub-Saharan Africa (SSA), which has 25%
      of the world's disease burden but only 1.3% of the world's health workforce. To
      prevent and treat HIV/AIDS, TB, malaria, and other maladies, the need is urgent
      to train and integrate the contributions of current workers who handle
      medications for major and minor health problems, especially those in licensed
      pharmacies and drug shops. On the aggregate in SSA, pharmaceutical care is in a
      nascent stage in most countries but needs to grow as a discipline as well as be
      tailored to specific country needs. The SSA solution lies in establishing health
      care system components where cadres of workers engage in pharmaceutical care
      practices, as well as store and distribute medications. Curriculum changes in pre
      service education, more continuing education for the health workforce in place,
      and training pharmacists to supervise a lower cadre of assistants and others are
      among the elements in a pharmaceutical care paradigm shift which is the focus of
      this article.

PMID- 19387997
TI  - The perceptions of Athenian physiotherapists on the referral service in Greece
      and its impact on professional autonomy.
AB  - BACKGROUND AND PURPOSE: The attainment of professional autonomy is considered a
      priority of any profession. The development of autonomy in physiotherapy has
      differed among countries, with some achieving a high degree of autonomy while
      others have struggled. The current literature reveals little about the autonomy
      of physiotherapists in Greece, although it would appear they face both external
      and internal threats to autonomous practice and to the development of their
      profession. This exploratory study investigated Athenian physiotherapists'
      experiences of the referral system in Greece and its impact on professional
      autonomy. METHODS: A qualitative, phenomenological approach was chosen, using a
      cluster sampling method. Ten physiotherapists participated in a 30-minute, one-to
      one, semi-structured interview. The interview audio tapes were transcribed and an
      inductive analysis was carried out. When all transcripts had been coded,
      categories and themes were compared to record commonalities and differences to
      construct a hierarchy of essential themes expressing general views. RESULTS:
      Physiotherapists were frustrated by the physiotherapy referral system in Greece.
      They revealed that their practice was restricted by factors, which included a
      long-standing dominance by the medical profession, bureaucratic process and the
      public perception of the profession in addition to restrictions from within the
      profession itself. To overcome the perceived restrictions to practice and the
      development of autonomy, participants had adopted strategies in an attempt to
      effectively address the patients' needs. CONCLUSIONS: There are clear issues
      related to the management and delivery of the physiotherapy referral system in
      Greece which impact on professional autonomy. Physiotherapists are forced to
      manipulate the referral system to provide a more appropriate level of care,
      resulting, however, in an inequitable service across the physiotherapy provision.
      If professional autonomy of physiotherapists in Greece is to move forward, these
      issues need to be acknowledged by governmental and professional bodies, as
      therapists can not be expected to undertake this journey alone.

PMID- 19387998
TI  - TENS and FES for sensory impairment and gait dysfunction following removal of
      spinal cord ependymoma--a case report.
AB  - BACKGROUND: Sensory deficits are commonly reported following the resection of
      spinal cord tumours. The use of transcutaneous electrical nerve stimulation
      (TENS) as augmented sensory input is described in the research literature but
      rarely in the clinical literature. Functional electrical stimulation (FES) is
      used for people with motor impairments rather than sensory impairments. METHOD
      AND RESULTS: This case report describes the use of TENS and FES for a patient
      with severe sensory loss and mild weakness in the right leg following the removal
      of an intramedullary spinal cord tumour. The patient was able to walk more
      quickly and more confidently when using TENS and FES in combination. She
      consistently reported greater benefits from TENS alone compared to FES alone and
      continued to use TENS delivered via a sock electrode at six months after surgery.
      CONCLUSION: The use of TENS as a sensory stimulus was an invaluable component of
      this patient's treatment, allowing her to engage in a more challenging balance
      and gait programme at an earlier stage in her rehabilitation. Combining FES with
      TENS was also useful and allowed treatment to address motor and sensory
      impairments concurrently during functional activity.

PMID- 19387999
TI  - Prevalence, risk factors and preventive strategies in work-related
      musculoskeletal disorders among Israeli physical therapists.
AB  - BACKGROUND AND PURPOSE: Although physical therapists (PTs) have extensive
      knowledge of body mechanisms and injury prevention, work-related musculoskeletal
      disorders (WRMD) are quite common in this population. The purposes of this study
      were: to determine the prevalence and impact of WRMD among Israeli PTs; to
      investigate WRMD risk factors and to identify preventive strategies used by PTs;
      and to compare the risk of injuries in two professional settings: rehabilitation
      centres (RCs) and outpatient clinics (OPCs). METHOD: A validated, modified Cromie
      questionnaire, translated into Hebrew, was distributed to the PTs at their
      workplaces. The relationship between WRMD symptoms and professional settings was
      analysed by Pearson chi-square. The risk models were developed by logistic
      regression. One hundred and twelve PTs working in OPCs and RCs who defined
      themselves as healthy individuals were the subjects of this study. RESULTS:
      Lifetime prevalence of WRMD was 83%. The highest prevalence of WRMD was in the
      lower back area (80%). Rehabilitation treatment was associated with an increased
      risk of lower back (odds ratio [OR] = 1.05) and shoulder symptoms (OR = 1.04);
      manual treatment was associated with an increased risk of wrist/thumb symptoms
      (OR = 1.11). DISCUSSION: Work in RCs was associated with an increased prevalence
      of lower back/shoulder symptoms, whereas work in OPCs was associated with an
      increased prevalence of thumb/wrist symptoms. PT's used different strategies to
      reduce risk of WRMD, including altering practice technique. The respondents
      recommended administrative and ergonomic changes in the workplace. CONCLUSION:
      Workplace-specific interventions to reduce WRMD in PTs should be developed and
      tested in future studies.

PMID- 19388000
TI  - ADHD and DAT1: further evidence of paternal over-transmission of risk alleles and
      haplotype.
AB  - We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over
      transmission of risk alleles in some ADHD-associated genes. This was particularly
      clear in the case of the DAT1 3'-UTR VNTR. In the current investigation, we
      analyzed three new sample comprising of 1,248 ADHD nuclear families to examine
      the allelic over-transmission of DAT1 in ADHD. The IMAGE sample, the largest of
      the three-replication samples, provides strong support for a parent of origin
      effect for allele 6 and the 10 repeat allele (intron 8 and 3'-UTR VNTR,
      respectively) of DAT1. In addition, a similar pattern of over-transmission of
      paternal risk haplotypes (constructed from the above alleles) was also observed.
      Some support is also derived from the two smaller samples although neither is
      independently significant. Although the mechanism driving the paternal over
      transmission of the DAT risk alleles is not known, these finding provide further
      support for this phenomenon.

PMID- 19388001
TI  - Quantification of J-resolved proton spectra in two-dimensions with LCModel using
      GAMMA-simulated basis sets at 4 Tesla.
AB  - A two-dimensional, J-resolved magnetic resonance spectroscopic extraction
      approach was developed employing GAMMA-simulated, LCModel basis-sets. In this
      approach, a two-dimensional J-resolved (2D-JPRESS) dataset was resolved into a
      series of one-dimensional spectra where each spectrum was modeled and fitted with
      its theoretically customized LCModel template. Metabolite levels were derived
      from the total integral across the J-series of spectra for each metabolite.
      Phantoms containing physiologic concentrations of the major brain chemicals were
      used for validation. Varying concentrations of glutamate and glutamine were
      evaluated at and around their accepted in vivo concentrations in order to compare
      the accuracy and precision of our method with 30 ms PRESS. We also assessed 2D
      JPRESS and 30 ms PRESS in vivo, in a single voxel within the parieto-occipital
      cortex by scanning ten healthy volunteers once and a single healthy volunteer
      over nine repeated measures. Phantom studies demonstrated that serial fitting of
      2D-JPRESS spectra with simulated LCModel basis sets provided accurate
      concentration estimates for common metabolites including glutamate and glutamine.
      Our in vivo results using 2D-JPRESS suggested superior reproducibility in
      measuring glutamine and glutamate relative to 30 ms PRESS. These novel methods
      have clear implications for clinical and research studies seeking to understand
      neurochemical dysfunction.

PMID- 19388002
TI  - Phenotypic effects of a bipolar liability gene among individuals with major
      depressive disorder.
AB  - Variations in voltage-dependent calcium channel L-type, alpha 1C subunit
      (CACNA1C) gene have been associated with bipolar disorder in a recent meta
      analysis of genome-wide association studies [Ferreira et al., 2008]. The impact
      of these variations on other psychiatric disorders has not been yet investigated.
      Caucasian non-Hispanic participants in the STAR*D study of treatment for
      depression for whom DNA was available (N = 1213) were genotyped at two single
      nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the CACNA1C gene.
      We examined putative phenotypic indicators of bipolarity among patients with
      major depression and elements of longitudinal course suggestive of latent
      bipolarity. We also considered remission and depression severity following
      citalopram treatment. The rs10848635 risk allele was significantly associated
      with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737
      risk allele was significantly associated with lesser baseline depression severity
      (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = 
      0.22). Both markers were associated with an increased risk of citalopram-emergent
      suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In
      this exploratory analysis, treatment-emergent suicidality was associated with two
      risk alleles in a putative bipolar liability gene.

PMID- 19388003
TI  - Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion
      injury via Akt-NOS signaling.
AB  - Ischemia/reperfusion (I/R) injury in cardiomyocytes is related to excess reactive
      oxygen species (ROS) generation and can be modulated by nitric oxide (NO). We
      have previously shown that grape seed proanthocyanidin extract (GSPE), a
      naturally occurring antioxidant, decreased ROS and may potentially stimulate NO
      production. In this study, we investigated whether GSPE administration at
      reperfusion was associated with cardioprotection and enhanced NO production in a
      cardiomyocyte I/R model. GSPE attenuated I/R-induced cell death [18.0 +/- 1.8%
      (GSPE, 50 microg/ml) vs. 42.3 +/- 3.0% (I/R control), P < 0.001], restored
      contractility (6/6 vs. 0/6, respectively), and increased NO release. The NO
      synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 200
      microM) significantly reduced GSPE-induced NO release and its associated
      cardioprotection [32.7 +/- 2.7% (GSPE + L-NAME) vs. 18.0 +/- 1.8% (GSPE alone), P
      < 0.01]. To determine whether GSPE induced NO production was mediated by the Akt
      eNOS pathway, we utilized the Akt inhibitor API-2. API-2 (10 microM) abrogated
      GSPE-induced protection [44.3% +/- 2.2% (GSPE + API-2) vs. 27.0% +/- 4.3% (GSPE
      alone), P < 0.01], attenuated the enhanced phosphorylation of Akt at Ser473 in
      GSPE-treated cells and attenuated GSPE-induced NO increases. Simultaneously
      blocking NOS activation (L-NAME) and Akt (API-2) resulted in decreased NO levels
      similar to using each inhibitor independently. These data suggest that in the
      context of GSPE stimulation, Akt may help activate eNOS, leading to protective
      levels of NO. GSPE offers an alternative approach to therapeutic cardioprotection
      against I/R injury and may offer unique opportunities to improve cardiovascular
      health by enhancing NO production and increasing Akt-eNOS signaling.

PMID- 19388004
TI  - TGFbeta regulation of membrane mucin Muc4 via proteosome degradation.
AB  - Muc4 is a heterodimeric membrane mucin implicated in epithelial differentiation
      and tumor progression. It is expressed from a single gene as a 300 kDa precursor
      protein which is cleaved in the endoplasmic reticulum to its two subunits. Our
      previous work has shown that Muc4 is regulated by TGFbeta, which represses the
      precursor cleavage. Working with Muc4-transfected A375 tumor cells, we now show
      that Muc4 undergoes proteosomal degradation. Proteosome inhibitors prolong the
      life of the precursor, shunt the Muc4 into cytoplasmic aggresomes, increase the
      level of Muc4 associated with the endoplasmic reticulum chaperones calnexin and
      calreticulin and increase the levels of ubiquitinated Muc4. Most importantly,
      proteosome inhibitors repress the TGFbeta inhibition of Muc4 expression. These
      results suggest a model in which TGFbeta inhibits precursor cleavage, shunting
      the precursor into the proteosomal degradation pathway. Thus, the cells have
      evolved a mechanism to use the quality control pathway for glycoproteins to
      control the quantity of the protein produced.

PMID- 19388005
TI  - The cardiac neural stem cell phenotype is compromised in streptozotocin-induced
      diabetic cardiomyopathy.
AB  - Neural stem cells were identified in the rat heart and during scar formation and
      healing participated in sympathetic fiber sprouting and angiogenesis. In the
      setting of diabetes, impaired wound healing represents a typical pathological
      feature. These findings provided the impetus to test the hypothesis that
      experimental diabetes adversely influenced the phenotype of cardiac neural stem
      cells. Streptozotocin (STZ)-induced diabetic rats were associated with elevated
      plasma glucose levels, significant loss of body weight and left ventricular
      contractile dysfunction. In the heart of STZ-diabetic rats, the density of nestin
      immunoreactive processes emanating from cardiac neural stem cells were reduced.
      The latter finding was reaffirmed as nestin protein expression was significantly
      decreased in the heart of STZ-diabetic rats and associated with a concomitant
      reduction of nestin mRNA. Employing the TUNEL assay, the loss of nestin
      expression in STZ-diabetic rats was not attributed to widespread cardiac neural
      stem cell apoptosis. Insulin administration to STZ-diabetic rats with established
      hyperglycaemia led to a modest recovery of nestin protein expression in cardiac
      neural stem cells. By contrast, the administration of insulin immediately after
      STZ injection improved plasma glucose levels and significantly attenuated the
      loss of nestin protein expression. These data highlight the novel observation
      that nestin protein expression in cardiac neural stem cells was significantly
      reduced in STZ-induced type I diabetic rats. The aberrant cardiac neural stem
      cell phenotype may compromise their biological role and predispose the diabetic
      heart to maladaptive healing following ischemic injury.

PMID- 19388007
TI  - Prevalence and longitudinal stability of negative symptoms in healthy
      participants.
AB  - OBJECTIVE: Although negative symptoms are prominent in older patients with
      schizophrenia, it is unknown whether this pattern is prevalent in healthy
      participants. The objective of this study was to evaluate whether negative
      symptoms are present in healthy populations and to determine whether they are
      linked to illness-related processes or normal aging. METHODS: A systemic review
      of 26 studies that have administered negative symptom assessments to healthy
      participants was conducted. In addition, 213 (age > 40 years old) healthy
      participants completed PANSS and SANS ratings at both baseline and 1-year follow
      up. One-hundred participants also completed ratings after 3 years. RESULTS:
      Across all reviewed studies, negative symptoms were absent in the majority of
      participants. Comparable results were found in the current study's large
      longitudinal evaluation with middle-aged to older adults. CONCLUSIONS: Taken
      together, the data suggest that healthy volunteers do not suffer from prominent
      negative symptoms. This finding is consistent with the hypothesis that the
      greater prevalence and severity of negative symptoms in older patients is not
      related to normal aging but to illness-related processes.

PMID- 19388006
TI  - On the assessment of cerebrovascular reactivity using hypercapnia BOLD MRI.
AB  - Cerebrovascular reactivity (CVR) reflects the capacity of blood vessels to dilate
      and is an important marker for brain vascular reserve. It may provide a useful
      addition to the traditional baseline blood flow measurement when assessing
      vascular factors in brain disorders. Blood-oxygenation-level-dependent MRI under
      CO(2) inhalation offers a non-invasive and quantitative means to estimate CVR in
      humans. In this study, we investigated several important methodological aspects
      of this technique with the goal of optimizing the experimental and data
      processing strategies for clinical use. Comparing 4 min of 5% CO(2) inhalation
      (less comfortable) to a 1 min inhalation (more comfortable) duration, it was
      found that the CVR values were 0.31 +/- 0.05%/mmHg (N = 11) and 0.31 +/-
      0.08%/mmHg (N = 9), respectively, showing no significant differences between the
      two breathing paradigms. Therefore, the 1 min paradigm is recommended for future
      application studies for patient comfort and tolerability. Furthermore, we have
      found that end-tidal CO(2) recording was useful for accurate quantification of
      CVR because it provided both timing and amplitude information regarding the input
      function to the brain vascular system, which can be subject-dependent. Finally,
      we show that inter-subject variations in CVR are of physiologic origin and affect
      the whole brain in a similar fashion. Based on this, it is proposed that relative
      CVR (normalized against the CVR of the whole brain or a reference tissue) may be
      a more sensitive biomarker than absolute CVR in clinical applications as it
      minimizes inter-subject variations. With these technological optimizations, CVR
      mapping may become a useful method for studies of neurological and psychiatric
      diseases.

PMID- 19388008
TI  - GilR, an unusual lactone-forming enzyme involved in gilvocarcin biosynthesis.
AB  - Last at last: The terminal step of the gilvocarcin V (GV) biosynthetic pathway is
      an unusual lactone formation. Here we show that the enzyme, GilR, dehydrogenates
      the hemiacetal moiety of pregilvocarcin V to the lactone found in GV by using
      covalently bound FAD.

PMID- 19388009
TI  - Near-infrared emission quantum yield of soluble short single-walled carbon
      nanotubes.
AB  - Soluble short single-walled carbon nanotubes in aerated D(2)O emit in the near
      infrared (NIR) region [picture: see text] with a quantum yield of (3.9+/-0.5)
      x10(-3) and a half-life of 7.65 micros. This emission is quenched by electron-
      acceptor molecules. Soluble short single-walled carbon nanotubes (sSWNT) are
      prepared by means of chemical fragmentation and purification of commercial SWNTs.
      The average length of the nanotubes, as estimated by microscopy, is 400 nm.
      Infrared spectroscopy studies reveal the presence of a significant population of
      carboxyl groups. The thermogravimetric profile of an sSWNT shows that this
      material is hydrophilic, contains carboxyl groups, and is almost free from
      inorganic impurities. In D(2)O solution, the obtained sSWNTs emit in the near
      infrared (NIR) region with a quantum yield of (3.9+/-0.5)x10(-3), determined
      using the 1270 nm singlet oxygen emission as a reference standard. The temporal
      profile can be fitted with first-order kinetics and a half-life of 13.9 micros.
      The NIR emission is quenched through a static mechanism by 2,4,6
      triphenylpyrylium (TP(+)), a typical electron acceptor.

PMID- 19388010
TI  - 3-hydroxy 3-methylglutaryl coenzyme A reductase increase is essential for rat
      muscle differentiation.
AB  - 3-Hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoAR) is the key and rate
      limiting enzyme of cholesterol biosynthetic pathway. Although HMG-CoAR activity
      has already been related to the differentiation of some cellular lines there are
      no studies that analyze the role of HMG-CoAR, and the pathway it is involved with
      in a fully characterized muscle differentiation model. Thus, the aim of this work
      is to evaluate such role and delineate the pathway involved in foetal rat
      myoblasts (L6) induced to differentiate by insulin -- a standard and feasible
      model of the myogenic process. The results obtained by biochemical and
      morphological approaches demonstrate that (i) HMG-CoAR increase is crucial for
      differentiation induction, (ii) p21waf, whose increase is a necessary requisite
      for differentiation to occur, rises downstream HMG-CoAR activation, (iii) the
      main role of p38/MAPK as key regulator also for HMG-CoAR. Pathologies
      characterized by muscle degeneration might benefit from therapeutic programmes
      committed to muscle function restoration, such as modulation and planning
      myoblast differentiation. Thus, the important role of HMG-CoAR in muscular
      differentiation providing new molecular basis for the control of muscle
      development can help in the design of therapeutic treatment for diseases
      characterized by the weakening of muscular fibers and aging-related disorders
      (sarcopenia).

PMID- 19388011
TI  - Asymmetric distribution of UCH-L1 in spermatogonia is associated with maintenance
      and differentiation of spermatogonial stem cells.
AB  - Asymmetric division of germline stem cells in vertebrates was proposed a century
      ago; however, direct evidence for asymmetric division of mammalian spermatogonial
      stem cells (SSCs) has been scarce. Here, we report that ubiquitin carboxy
      terminal hydrolase 1 (UCH-L1) is expressed in type A (A(s), A(pr), and A(al))
      spermatogonia located at the basement membrane (BM) of seminiferous tubules at
      high and low levels, but not in differentiated germ cells distant from the BM.
      Asymmetric segregation of UCH-L1 was associated with self-renewal versus
      differentiation divisions of SSCs as defined by co-localization of UCH-L1(high)
      and PLZF, a known determinant of undifferentiated SSCs, versus co-localization of
      UCH-L1(low/-) with proteins expressed during SSC differentiation (DAZL, DDX4, c
      KIT). In vitro, gonocytes/spermatogonia frequently underwent asymmetric divisions
      characterized by unequal segregation of UCH-L1 and PLZF. Importantly, we could
      also demonstrate asymmetric segregation of UCH-L1 and PLZF in situ in
      seminiferous tubules. Expression level of UCH-L1 in the immature testis where
      spermatogenesis was not complete was not affected by the location of germ cells
      relative to the BM, whereas UCH-L1-positive spermatogonia were exclusively
      located at the BM in the adult testis. Asymmetric division of SSCs appeared to be
      affected by interaction with supporting somatic cells and extracelluar matrix.
      These findings for the first time provide direct evidence for existence of
      asymmetric division during SSCs self-renewal and differentiation in mammalian
      spermatogenesis.

PMID- 19388012
TI  - Retinoid-responsive transcriptional changes in epidermal keratinocytes.
AB  - Retinoids (RA) have been used as therapeutic agents for numerous skin diseases,
      from psoriasis to acne and wrinkles. While RA is known to inhibit keratinocyte
      differentiation, the molecular effects of RA in epidermis have not been
      comprehensively defined. To identify the transcriptional targets of RA in primary
      human epidermal keratinocytes, we compared the transcriptional profiles of cells
      grown in the presence or absence of all-trans retinoic acid for 1, 4, 24, 48, and
      72 h, using large DNA microarrays. As expected, RA suppresses the protein markers
      of cornification; however the genes responsible for biosynthesis of epidermal
      lipids, long-chain fatty acids, cholesterol, and sphingolipids, are also
      suppressed. Importantly, the pathways of RA synthesis, esterification and
      metabolism are activated by RA; therefore, RA regulates its own bioavailability.
      Unexpectedly, RA regulates many genes associated with the cell cycle and
      programmed cell death. This led us to reveal novel effects of RA on keratinocyte
      proliferation and apoptosis. The response to RA is very fast: 315 genes were
      regulated already after 1 h. More than one-third of RA-regulated genes function
      in signal transduction and regulation of transcription. Using in silico analysis,
      we identified a set of over-represented transcription factor binding sites in the
      RA-regulated genes. Many psoriasis-related genes are regulated by RA, some
      induced, others suppressed. These results comprehensively document the
      transcriptional changes caused by RA in keratinocytes, add new insights into the
      molecular mechanism influenced by RA in the epidermis and demonstrate the
      hypothesis-generating power of DNA microarray analysis.

PMID- 19388013
TI  - BDNF, relative preference, and reward circuitry responses to emotional
      communication.
AB  - Brain derived neurotrophic factor (BDNF) regulates neural development and
      synaptic transmission. We have tested the hypothesis that functional variation in
      the BDNF gene (Val66Met polymorphism, rs6265) affects brain reward circuitry
      encoding human judgment and decision-making regarding relative preference. We
      quantified relative preference among faces with emotional expressions (angry,
      fearful, sad, neutral, and happy) by a keypress procedure performed offline to
      measure effort traded for viewing time. Keypress-based relative preferences
      across the ensemble of faces were mirrored significantly by fMRI signal in the
      orbitofrontal cortex, amygdala, and hippocampus when passively viewing these
      faces. For these three brain regions, there was also a statistically significant
      group difference by BDNF genotype in the fMRI responses to the emotional
      expressions. In comparison with Val/Met heterozygotes, Val/Val individuals
      preferentially sought exposure to positive emotions (e.g., happy faces) and had
      stronger regional fMRI activation to aversive stimuli (e.g., angry, fearful, and
      sad faces). BDNF genotype accounted for approximately 30% of the variance in fMRI
      signal that mirrors keypress responses to these stimuli. This study demonstrates
      that functional allelic variation in BDNF modulates human brain circuits
      processing reward/aversion information and relative preference transactions.

PMID- 19388015
TI  - Trichloroacetic acid-induced protein precipitation involves the reversible
      association of a stable partially structured intermediate.
AB  - Sample preparation for proteomic analysis involves precipitation of protein using
      2,2,2-trichloroacetic acid (TCA). In this study, we examine the mechanism of the
      TCA-induced protein precipitation reaction. TCA-induced protein precipitation
      curves are U-shaped and the shape of the curve is observed to be independent of
      the physicochemical properties of proteins. TCA is significantly less effective
      in precipitating unfolded states of proteins. Results of the 1-anilino-8
      napthalene sulfonate (ANS) and size-exclusion chromatography, obtained using
      acidic fibroblast growth factor (aFGF), show that a stable "molten globule-like"
      partially structured intermediate accumulates maximally in 5% (w/v) of
      trichloroacetate. Urea-induced unfolding and limited proteolytic digestion data
      reveal that the partially structured intermediate is significantly less stable
      than the native conformation. (1)H-(15)N chemical shift perturbation data
      obtained using NMR spectroscopy indicate that interactions stabilizing the beta
      strands at the N- and C- terminal ends (of aFGF) are disrupted in the
      trichloroacetate-induced "MG-like" state. The results of the study clearly
      demonstrate that TCA-induced protein precipitation occurs due to the reversible
      association of the "MG-like" partially structured intermediate state(s). In our
      opinion, the findings of this study provide useful clues toward development of
      efficient protocols for the isolation and analysis of the entire proteome.

PMID- 19388016
TI  - A highly sensitive fluorescence probe for fast thiol-quantification assay of
      glutathione reductase.
AB  - Fast detection of cellular thiols in aqueous medium was achieved using a newly
      developed fluorescence probe (see picture). Based on this probe, a high
      throughput fluorescence assay for glutathione reductase was developed.

PMID- 19388017
TI  - Metabolic labeling of sialic acids in living animals with alkynyl sugars.
AB  - Sialome sweet sialome: As sialic acids are involved in many host-pathogen
      recognition events and are markers of embryonic and malignant tissues, there is
      great interest in methods for the enrichment and identification of sialylated
      glycoproteins from complex tissues. Now N-(4-pentynoyl)mannosamine can be used to
      metabolically label sialylated glycoproteins in living animals, enabling future
      identification of new biomarkers.

PMID- 19388018
TI  - Stable cyclohexyl-phenyl recognition in the center of a DNA duplex.
AB  - Even saturated carbocycles are compatible with Watson-Crick pairing, as shown by
      the incorporation of phenylcyclohexyl-C-nucleoside pairs into the center of a DNA
      double helix (see picture). The increase in duplex stability arises from
      cyclohexyl/phenyl CH/pi interactions. This makes the system an interesting
      scaffold for studying hydrophobic interactions and allows for the incorporation
      of additional molecular entities into the double helix.

PMID- 19388019
TI  - An aqueous route to multicolor photoluminescent carbon dots using silica spheres
      as carriers.
AB  - Carbon lights up: A facile chemical method yields multicolor photoluminescent
      carbon dots derived from polymer/silica nanocomposites, which were prepared using
      surfactant-modified silica spheres as carriers and resols (phenol/formaldehyde
      resins) as carbon precursor (see picture). The surface-passivated carbon dots
      show good biocompatibility as potential bioimaging agents offering nanometer
      scale resolution.

PMID- 19388020
TI  - Multistep synthesis using modular flow reactors: Bestmann-Ohira reagent for the
      formation of alkynes and triazoles.
AB  - Multistep in flow: The Seyferth-Gilbert reagent 1 has been applied in a flow
      system to rapidly synthesize terminal alkynes. The system has been further
      applied to synthesize triazole 3 from alcohol 2 in a three-step
      oxidation/homologation/copper(I)-catalyzed azide-alkyne cycloaddition sequence
      without isolation of intermediates (see scheme).

PMID- 19388021
TI  - Sequence requirement and subtype specificity in the high-affinity interaction
      between human frizzled and dishevelled proteins.
AB  - Members of the Wnt family of lipoglycoproteins initiate signaling by binding to
      Frizzled (Fz) receptors, and the signal is then relayed by Disheveled (Dvl). The
      Dvl PDZ domain is known to interact directly with a peptide derived from the
      KTXXXW motif of Fz7, which is conserved in all known Fz subtypes. We found that
      an extended region spanning the KTXXXW motif on both its N-terminal and C
      terminal sides dramatically influences the affinity of peptides derived from Fz7
      for Dvl PDZ. An alanine scanning study identified the specific residues external
      to the KTXXXW motif that are important for high-affinity binding. In a circular
      dichroism analysis, mutation of some of these critical residues resulted in
      peptide conformational changes, suggesting that the secondary structure of the
      peptides contributes to Fz-Dvl PDZ binding. Of the 10 known Fz subtypes, peptides
      derived from only Fz1, Fz2, Fz3, Fz4, and Fz7 directly bound to Dvl PDZ domain in
      our study. Other Fz subtypes, including some known to be involved in Wnt/beta
      catenin signaling (Fz5, Fz9), did not bind to Dvl, suggesting that direct
      interaction with Dvl PDZ does not determine the subtype-specific functionality of
      Fz. Molecular modeling and circular dichroism studies indicated that the Fz
      peptides that bind to Dvl PDZ domain form specific conformations that are
      different from those of nonbinding peptides.

PMID- 19388022
TI  - Activation of the West Nile virus NS3 protease: molecular dynamics evidence for a
      conformational selection mechanism.
AB  - The flaviviral nonstructural 3 protease (NS3pro) is essential for virus
      replication and is therefore a pharmaceutically relevant target to fight Dengue
      and West Nile virus (WNV). NS3pro is a chymotrypsin-like serine protease which
      requires a polypeptide cofactor (NS2B) for activation. Recent X-ray
      crystallography studies have led to the suggestion that the substrate binds to
      the two-component NS2B-NS3pro enzyme by an induced-fit mechanism. Here, multiple
      explicit water molecular dynamics simulations of the WNV NS2B-NS3pro enzyme show
      that the active conformation of the NS2B cofactor (in which its beta-loop is part
      of the substrate binding site) is stable over a 50-ns time scale even in the
      absence of the inhibitor. The partial and reversible opening of the NSB2 beta
      loop and its correlated motion with an adjacent NS3pro loop, both observed in the
      simulations started from the active conformation, are likely to facilitate
      substrate binding and product release. Moreover, in five of eight simulations
      without inhibitor (started from two X-ray structures both with improperly formed
      oxyanion hole) the Thr132-Gly133 peptide bond flips spontaneously thereby
      promoting the formation of the catalytically competent oxyanion hole, which then
      stays stable until the end of the runs. The simulation results provide evidence
      at atomic level of detail that the substrate binds to the NS2B-NS3pro enzyme by
      conformational selection, rather than induced-fit mechanism.

PMID- 19388023
TI  - Engineered disulfides improve mechanical properties of recombinant spider silk.
AB  - Nature's high-performance polymer, spider silk, is composed of specific proteins,
      spidroins, which form solid fibers. So far, fibers made from recombinant
      spidroins have failed in replicating the extraordinary mechanical properties of
      the native material. A recombinant miniature spidroin consisting of four poly
      Ala/Gly-rich tandem repeats and a nonrepetitive C-terminal domain (4RepCT) can be
      isolated in physiological buffers and undergoes self assembly into macrofibers.
      Herein, we have made a first attempt to improve the mechanical properties of
      4RepCT fibers by selective introduction of AA --> CC mutations and by letting the
      fibers form under physiologically relevant redox conditions. Introduction of AA -
      > CC mutations in the first poly-Ala block in the miniature spidroin increases
      the stiffness and tensile strength without changes in ability to form fibers, or
      in fiber morphology. These improved mechanical properties correlate with degree
      of disulfide formation. AA --> CC mutations in the forth poly-Ala block, however,
      lead to premature aggregation of the protein, possibly due to disulfide bonding
      with a conserved Cys in the C-terminal domain. Replacement of this Cys with a
      Ser, lowers thermal stability but does not interfere with dimerization, fiber
      morphology or tensile strength. These results show that mutagenesis of 4RepCT can
      reveal spidroin structure-activity relationships and generate recombinant fibers
      with improved mechanical properties.

PMID- 19388024
TI  - Classic paper: How monolayer cell culture transformed diagnostic virology: a
      review of a classic paper and the developments that stemmed from it. (Science,
      New Series, Vol. 109, No. 2822 (Jan. 28, 1949), pp. 85-87).

PMID- 19388025
TI  - Cooperative metal binding and helical folding in model peptides of treble-clef
      zinc fingers.
AB  - Two peptides, L(TC) and L(TC)(T) have been synthesised to model the treble-clef
      zinc fingers encountered in many Zn(Cys)(4)-site-containing proteins. Both are
      cyclic peptides with a linear tail grafted on a glutamate side chain of the
      cycle. They differ by the length of this tail, which lacks five amino acids in
      L(TC)(T) compared to L(TC). Both peptides bind Zn(2+) and Co(2+) in 1:1
      metal/peptide ratio and the structure of these complexes have been characterised
      by NMR, UV/Vis and CD spectroscopy. Both peptides fold the same way around the
      metal ion and they fully reproduce the classical fold of treble-clef zinc fingers
      and display an extended hydrogen-bond network around the coordinating sulfur
      atoms. The structures of the ML(TC) complexes reveal that the linear tail forms a
      short two-turn alpha-helix, present in the metallated form only. The formation of
      this helix constitutes a rare example of metal-induced folding. The second turn
      of this helix is composed of the five amino acids that are absent in L(TC)(T).
      The study of the pH-dependence of the Zn(2+) binding constants shows that the
      metal ion is bound by four cysteinates above pH 5.2 and the binding constants are
      the highest reported so far. Interestingly, the binding constant of Zn x L(TC) is
      about tenfold higher than that of Zn x L(TC)(T). This difference clearly
      indicates that the helix, present in Zn x L(TC) only, stabilises the Zn(2+)
      complex by about 1.2 kcal mol(-1). The origin of this stabilisation is ascribed
      to an electrostatic interaction between the [ZnS(4)](2-) centre and the helix.
      This reveals a cooperative effect: zinc binding allows the folding of the tail
      into a helix which, in turn, strengthens the zinc complex.

PMID- 19388026
TI  - Fluorinated carbohydrates as lectin ligands: versatile sensors in 19F-detected
      saturation transfer difference NMR spectroscopy.
AB  - As a novel approach for studying carbohydrate-lectin interactions
      spectroscopically, we combine the resolution and specificity of (19)F-detected
      NMR spectroscopy with the sensitivity of the saturation transfer difference (STD)
      technique. The resulting background-free (19)F-STD spectra open a promising
      perspective for broad application with medical relevance, for example, in drug
      discovery.

PMID- 19388027
TI  - Coherently aligned porphyrin-appended polynorbornenes.
AB  - Six different kinds of coherently aligned porphyrin-appended polynorbornenes
      derived from 5,6-endo-fused N-arylpyrrolidenonorbornenes have been synthesized.
      Pi-pi interactions between the pendant groups are essential for dictating the
      photophysical properties of the polymers and the mechanism for the
      stereoselective formation of polymers. Splitting of the Soret band of polymers 2a
      c, which have alkyl-substituted porphyrin pendant groups, suggests strong exciton
      coupling between chromophores. No splitting of the Soret band is observed for
      polymers 2d-f, which have tetraaryl substituents on the porphyrin moiety.
      Significant fluorescence quenching is found in polymers 2a-e, whereas only
      slightly reduced quantum yield is observed for 2f. Time-resolved fluorescence
      measurements also indicate a similar trend. The AFM image of 2d on graphite shows
      aggregation to form a two-dimensional, ordered pattern.

PMID- 19388028
TI  - Robust self-assembled monolayers of Ru(II) and Os(II) polypyridines on gold
      surfaces: exploring new potentials.
AB  - Metal complexes [M(phtpy)(pztpy)](PF(6))(2) (phtpy = 4'-phenyl-2,2':6',2''
      terpyridine, pztpy = 4'-(N-piperazinyl)-2,2':6',2''-terpyridine, M = Ru, Os) were
      prepared and examined spectroscopically and electrochemically. The piperazine
      attachment was found to significantly modify the photophysical and
      electrochemical properties compared to the parent bis-terpyridine complexes,
      causing a red-shift of the (1)MLCT (23 nm, 53.9 eV) and a substantial cathodic
      shift of the redox potential (0.3 V for Ru, 0.23 V for Os). Self-assembled
      monolayers (SAMs) of the complexes on polished gold electrodes were generated
      simply by the in situ formation of a dithiocarbamate (DTC) anchoring group at the
      terminal piperazinyl nitrogen on the pztpy ligand. Cyclic voltammetry revealed
      that the monolayers show excellent reversible behaviour and exceptional
      stability. The high stability of the SAMs is attributed to the strong bidentate
      attachment to the gold surface of the DTC tether and the favourable low oxidation
      potentials of the complexes which result from the electron-rich piperazine
      nitrogen on the pztpy ligand. Such DTC-based SAMs demonstrate a substantial
      improvement over commonly-employed thiol-based systems, and offer new scope for
      future development.

PMID- 19388029
TI  - Mechanistic investigations into the asymmetric transfer hydrogenation of ketones
      catalyzed by pseudo-dipeptide ruthenium complexes.
AB  - The combination of N-Boc-protected alpha-amino acid hydroxyamides (pseudo
      dipeptides) and [{Ru(p-cymene)Cl(2)}(2)] resulted in the formation of superior
      catalysts for the asymmetric transfer hydrogenation (ATH) of non-activated aryl
      alkyl ketones in propan-2-ol. The overall kinetics of the ATH of acetophenone to
      form 1-phenylethanol in the presence of ruthenium pseudo-dipeptide catalysts were
      studied, and the individual rate constants for the processes were determined.
      Addition of lithium chloride to the reaction mixtures had a strong influence on
      the rates and selectivities of the processes. Kinetic isotope effects (KIEs) for
      the reduction were determined and the results clearly show that the hydride
      transfer is rate-determining, whereas no KIEs were detected for the proton
      transfer. From these observations a novel bimetallic outer-sphere-type mechanism
      for these ATH process is proposed, in which the bifunctional catalysts mediate
      the transfer of a hydride and an alkali metal ion between the hydrogen donor and
      the substrate. Furthermore, the use of a mixture of propan-2-ol and THF (1:1)
      proved to enhance the rates of the ATH reactions. A series of aryl alkyl ketones
      were reduced under these conditions in the presence of 0.5 mol % of catalyst, and
      the corresponding secondary alcohols were formed in high yields and with
      excellent enantioselectivities (>99% ee) in short reaction times.

PMID- 19388030
TI  - Rhodium(I)-catalysed intramolecular [2+2+2] cyclotrimerisations of 15-, 20- and
      25-membered azamacrocycles: experimental and theoretical mechanistic studies.
AB  - A new series of 20- and 25-membered polyacetylenic azamacrocycles have been
      satisfactorily prepared and completely characterised by spectroscopic methods.
      Various [2+2+2] cyclotrimerisation processes catalysed by the Wilkinson's
      catalyst, [RhCl(PPh(3))(3)], were tested in the above-mentioned macrocycles. The
      25-membered azamacrocycle (like the previously synthesised 15-membered
      azamacrocyle) led to the expected cyclotrimerised compound in contrast to the 20
      membered macrocycle, which is characterised by its lack of reactivity. The
      difference in reactivity of the 15-, 20- and 25-membered macrocycles has been
      rationalised through density functional theory calculations.

PMID- 19388031
TI  - The synthesis, full characterisation and utilisation of template-free silica
      sodalite, a novel polymorph of silica.
AB  - Empty glass: Subjecting ethylene glycol silica sodalite to heat (680 degrees C)
      under a nitrogen atmosphere (i) successfully removes the templating agent to give
      cubic silica sodalite, which, upon consequent heating under an oxygen atmosphere
      (ii), transforms into a rhombohedral form of the empty sodalite, in effect a
      novel polymorph of silica.

PMID- 19388032
TI  - Dihydrogen bonding: donor-acceptor bonding (AH...HX) versus the H2 molecule (A-H2
      X).
AB  - Dihydrogen bonds (DHBs) play a role in, among others, crystal packing,
      organometallic reaction mechanisms, and potential hydrogen-storage materials. In
      this work we have analyzed the central H-H bond in linear H(4), LiH...HX, BH(4)(
      )...HX, and AlH(4)(-)...HX complexes with various X by using the quantitative
      molecular orbital model contained in Kohn-Sham density functional theory at the
      BP86/TZ2P level of theory. First, we address the questions of if and how one can
      distinguish, in principle, between a H...H donor-acceptor DHB and the formation
      of an H(2) molecule by using the simple H(4) model system. The results of these
      analyses have been used to gain an understanding of the bonding in more realistic
      model systems (some of which have been studied experimentally), and how this
      differs from the bonding in H(4).

PMID- 19388033
TI  - Michael additions versus cycloaddition condensations with ethyl nitroacetate and
      electron-deficient olefins.
AB  - Ethyl nitroacetate (1) reacts with electron-poor olefins in the presence of a
      base to give either the Michael adducts 3 or the isoxazoline cycloadducts 4,
      resulting from water elimination. The proportions of the two products depend on
      the reaction conditions and change in the course of the process. Kinetic profiles
      for the two reactions show that the cycloaddition-condensations require long
      induction times that dramatically decrease upon addition of a copper salt to the
      catalytic system: the drops in the induction time cause increases in the
      proportion of cycloadducts 4, which are often the sole reaction products. This is
      the first report on the selective formation of products 3 and 4 from primary
      nitro compounds through modulation of the catalytic system.

PMID- 19388034
TI  - The evaluation of delirium post-stroke.
AB  - OBJECTIVE: The aim of this study was to assess and compare the Confusion
      Assessment Method (CAM) and the Delirium Rating Scale (DRS) in the detection of
      delirium in the acute stroke setting, when used by a non-psychiatrist doctor.
      METHODS: Consecutive participants within 4 days of an acute stroke were screened
      for delirium using the CAM and the DRS. Patients also had a Mini-Mental State
      Examination at each assessment. Patients were screened weekly for a maximum of 4
      weeks. The CAM and DRS were compared against each other with respect to agreement
      and applicability. RESULTS: Of 110 eligible patients, 82 were recruited over a 7
      month period. Delirium developed in 23 patients (28%), 21 of whom developed
      delirium during week 1. We found high agreement between the CAM and the DRS in
      the detection of stroke in the acute stroke setting (kappa values 0.97, 0.86,
      0.79 and 1 at weeks 1, 2, 3 and 4, respectively). In addition, there was strong
      correlation between low MMSE scores (MMSE less that 10) and delirium (kappa
      scores 1.0, 0.82, 0.83 and 1.0 at weeks 1, 2, 3 and 4, respectively).
      CONCLUSIONS: Delirium is a common complication post-stroke. The CAM is equivalent
      to the DRS in the acute stroke setting when used by a trained non-psychiatrist. A
      low MMSE score may have a small benefit in identifying patients that are at risk
      of having delirium.

PMID- 19388035
TI  - "Catalysis in a tea bag": synthesis, catalytic performance and recycling of
      dendrimer-immobilised bis- and trisoxazoline copper catalysts.
AB  - Bis- and trisoxazolines (BOX and trisox), containing a linker unit in the ligand
      backbone that allows their covalent attachment to carbosilane dendrimers, have
      been employed as polyfunctional ligands for recyclable Cu(II) Lewis acid
      catalysts that were immobilised in a membrane bag. The oxazolines contained an
      alkynyl unit attached to their backbone that was deprotonated with LDA or BuLi
      and then reacted with the chlorosilyl termini of zeroth-, first- and second
      generation carbosilane dendrimers in the presence of TlPF(6). The functionalised
      dendritic systems were subsequently separated from excess ligand by way of
      dialysis. The general catalytic potential of these systems was assessed by
      studying two benchmark reactions, the alpha-hydrazination of a beta-keto ester as
      well as the Henry reaction of 2-nitrobenzaldehyde with nitromethane. For both
      reactions the bisoxazoline-based catalysts displayed superior selectivity and, in
      particular, catalyst activity. The latter was interpreted as being due to the
      hindered decoordination of the third oxazoline unit, the key step in the
      generation of the active catalyst, in the immobilised trisox-copper complexes.
      Solutions of the second-generation dendrimer catalysts were placed in membrane
      bags, fabricated from commercially available dialysis membranes, with the purpose
      of catalyst recycling based on dialysis. Overall, the supported BOX catalyst gave
      good and highly reproducible results throughout the study, whereas the
      performance of the trisox dendrimer system decreased monotonically. The reason
      for the different behaviour is the markedly lower activity of trisox-based
      catalysts relative to those based on the BOX ligand. This necessitated an
      increased reaction time for each cycle of the trisox derivatives, resulting in
      higher levels of catalyst leaching, which was attributed to a modification of the
      structure of the membrane by its exposure to the solvent trifluoroethanol at 40
      degrees C.

PMID- 19388036
TI  - Solid-state structure of free base guanidine achieved at last.
AB  - "Crystal structure of the free base guanidine determined 148 years after the
      first synthesis": A prototype structure unveiled--despite its provocative
      simplicity, the crystal structure of guanidine has not been previously described.
      148 years after the first synthesis of guanidine, we now find two Y-shaped
      symmetry-independent molecules in the unit cell that are interconnected by a
      hydrogen-bonding network, which results in a fascinating layered structure (see
      picture).

PMID- 19388037
TI  - Anion-templated formation of supramolecular multinuclear assemblies.
AB  - The use of anions as supramolecular building motifs is reported herein. The
      interaction of various anions with [Zn(salphen)] complexes (salphen = N,N'
      phenylenebis(salicylideneimine)) has been studied, with a particular focus on
      assembly formation in the presence of acetate anions. Strong association of the
      latter with the Zn metal centre of the salphen complex was quantified by UV/Vis
      titration studies. The [Zn(salphen)]-OAc assemblies were further characterized by
      NMR spectroscopy and X-ray analysis and revealed that the acetate anions can
      function as bridging modules between two [Zn(salphen)] units. The binding
      strength of a second complex to the acetate anion may be regulated by the
      substitution pattern of the salphen ligand. The anion-templated assembly
      formation was further demonstrated by the supramolecular synthesis of a
      trinuclear Zn(3) assembly. These results hold promise for the directed assembly
      formation of [Zn(salphen)] complexes with biologically relevant carboxylates,
      such as amino acids, and potentially new bio-sensing materials.

PMID- 19388038
TI  - The first magnetic nanoparticle-supported chiral DMAP analogue: highly
      enantioselective acylation and excellent recyclability.
AB  - Recyclable organocatalysts: The first chiral DMAP analogue immobilized on
      magnetic nanoparticles is a highly active catalyst that is capable of the
      acylation of racemic sec-alcohols under convenient, process-scale friendly
      conditions (room temperature, 5 mol % loading, with acetic anhydride as the
      acylating agent) with excellent enantiodiscrimination. The catalyst is easily
      recovered and possesses unprecedented recyclability-in this study it was
      demonstrated to retain excellent activity and selectivity over 32 iterative
      cycles.

PMID- 19388039
TI  - Stepwise conversion of two pyrrole moieties of octaethylporphyrin to pyridin-3
      ones: synthesis, mass spectral, and photophysical properties of mono and
      bis(oxypyri)porphyrins.
AB  - Free-base octaethylporphyrin (OEP) was converted in two steps (beta,beta'
      dihydroxylation and oxidative diol cleavage with concomitant aldol condensation)
      to the corresponding oxypyriporphyrin. This conversion was previously described
      to be applicable only to the Ni(II) complex of OEP. Modified diol cleavage
      conditions made this reaction sequence now applicable to free-base OEP. The
      single-crystal structure of the resulting free-base oxypyriporphyrin was
      determined, proving its near-perfect planarity. The reaction sequence can also be
      applied to oxypyriporphyrin itself, generating the unprecedented bacteriochlorin
      type bis(oxypyri)porphyrin as two separable isomers. The ground-state (UV/Vis and
      fluorescence spectroscopies) and excited-state (transient triplet-triplet
      absorption, triplet lifetimes, and triplet EPR spectroscopy) photophysical
      properties of all chromophores are compared with those of OEP, chlorins, and
      oxochlorins. The pyridone-modified porphyrins possess unique spectroscopic
      signatures that distinguish them from regular porphyrins or chlorins. The
      presence of the pyridone moiety alters the ESI(+) collision-induced fragmentation
      properties of these oxypyriporphyrins only to a minor degree when compared with
      those of OEP or chlorins, confirming their stability.

PMID- 19388040
TI  - Versatile reactivity of a zwitterionic isolable silylene toward ketones: silicon
      mediated, regio- and stereoselective C-H activation.
AB  - Reactions of the isolable, ylide-like silylene LSi: (1) (L =
      CH[(C=CH(2))CMe][N(Ar)](2), Ar = 2,6-iPr(2)C(6)H(3)) with different ketones
      (benzophenone, benzylideneaceton, acetophenone) have been investigated. The
      metastable dearomatized siloxindane 2, which was suggested previously as reaction
      intermediate but could not be detected in related reactions, has been obtained
      for the first time from the regio- and stereoselective addition of silylene 1 to
      benzophenone at low temperature. By variation of the reaction temperature, the
      initial product 2 rearranges under re-aromatization stereoselectively to the
      corresponding siloxindane 3, which has also been isolated in high yield. In
      contrast, reactions of 1 with benzylidenacetone and acetophenone furnish the
      [4+1] cycloaddition product 4 and the silyl enol ether 5, respectively. It is
      proposed that in all reactions the 1,4-dipolar nature of 1 plays key role,
      leading to highly reactive donor-acceptor adducts, which undergo rearrangement
      (tautomerization) to the final products. The new compounds 2, 3, 4, and 5 were
      characterized by (1)H, (13)C, and (29)Si NMR spectroscopy, EI-MS, and elemental
      analysis, and their structures determined by single-crystal X-ray diffraction
      analysis.

PMID- 19388041
TI  - Gold-catalyzed reactions of 1,5- and 1,6-enynes with carbonyl compounds:
      cycloaddition vs. metathesis.
AB  - Gold and rings: The gold(I)-catalyzed addition of aldehydes to 1,6-enynes gives
      1,3-dienes, by a cycloaddition/fragmentation process. 1,5-Enynes react with
      aldehydes and ketones by the 5-endo-dig pathway to give the corresponding
      cycloadducts.

PMID- 19388042
TI  - DNA-assisted self-assembly of pyrene foldamers.
AB  - The self-organization of oligopyrene foldamers is described. Bi- and tri
      segmental oligomers composed of nucleotides and non-nucleosidic, achiral pyrene
      monomers form double-stranded helical structures, as shown by absorbance,
      fluorescence, and CD spectroscopy. The mixed nature of alternating aromatic and
      phosphate groups ensures water solubility which, in turn, favors folding of the
      aromatic units. Pyrene molecules also assemble though interstrand stacking
      interactions. Structural organization of the pyrene units is an intrinsic
      property of the oligoaryl part and takes place independently from the sequence of
      the attached DNA. Chirality transfer from DNA to the pyrene segment leads to
      formation of a double helix, in which neighboring pyrene units are, in the
      present case, twisted in a right-handed manner. Pyrene helicity is most
      pronounced in a bi-segmental chimera, in which a DNA stem is present only at one
      end of the pyrene section.

PMID- 19388043
TI  - Three-component synthesis of highly functionalized 5-acetyloxazoles.
AB  - By a flexible three-component synthesis, alkoxy-substituted enamides are easily
      available from lithiated alkoxyallenes, nitriles and carboxylic acids (see
      scheme). The treatment of these versatile intermediates with trifluoroacetic acid
      provided 5-acetyloxazoles in moderate to good yields. Different substituents are
      possible at C-2 and C-5 and the 5-acetyl group is a suitable handle for further
      synthetic transformations.

PMID- 19388044
TI  - Self-assembly of Mn-doped ZnS quantum dots/octa(3-aminopropyl)octasilsequioxane
      octahydrochloride nanohybrids for optosensing DNA.
AB  - Simple plan! Nanohybrids have been built from capped Mn-doped ZnS quantum dots
      and octa(3-aminopropyl)octasilsequioxane octahydrochloride (OA-POSS) by means of
      electrostatic self-assembly for the development of a novel room-temperature
      phosphorescence sensor for DNA sensing in biological fluids (see graphic).

PMID- 19388045
TI  - Thermodynamic controlled hierarchical assembly of ternary supramolecular networks
      at the liquid-solid interface.
AB  - Building and networking: Ternary supramolecular networks have been formed by
      coadsorption of dissimilar ternary building units at the liquid-solid interface.
      The structural characteristics of the networks undergo distinctive
      transformations as the building units change from binary to ternary components
      (see graphic).

PMID- 19388047
TI  - The beginning of the end of a long wait for a vaccine against cytomegalovirus.

PMID- 19388048
TI  - A method for site-specific labeling of multiple protein thiols.
AB  - We present a generic method for the site-specific and differential labeling of
      multiple cysteine residues in one protein. Phenyl arsenic oxide has been employed
      as a protecting group of two closely spaced thiols, allowing first labeling of a
      single thiol. Subsequently, the protecting group is removed, making available a
      reactive dithiol site for labeling with a second probe. For proof-of-principle,
      single and triple Cys mutants of the sulphate binding protein of an ABC
      transporter were constructed. The closely spaced thiols were engineered on the
      basis of the crystal structure of the protein and placed in different types of
      secondary structure elements and at different spacing. We show that phenyl
      arsenic oxide is a good protecting group for thiols spaced 6.3-7.3 A. Proteins
      were labeled with two different fluorescent labels and the labeling ratios were
      determined with UV-Vis spectroscopy and MALDI-Tof mass spectrometry. The average
      labeling efficiency was approximately 80% for the single thiol and 65-90% for the
      dithiol site.

PMID- 19388049
TI  - Rational redesign of neutral endopeptidase binding to merlin and moesin proteins.
AB  - Neutral endopeptidase (NEP) is a 90- to 110-kDa cell-surface peptidase that is
      normally expressed by numerous tissues but whose expression is lost or reduced in
      a variety of malignancies. The anti-tumorigenic function of NEP is mediated not
      only by its catalytic activity but also through direct protein-protein
      interactions of its cytosolic region with several binding partners, including Lyn
      kinase, PTEN, and ezrin/radixin/moesin (ERM) proteins. We have previously shown
      that mutation of the K(19)K(20)K(21) basic cluster in NEPs' cytosolic region to
      residues QNI disrupts binding to the ERM proteins. Here we show that the ERM
      related protein merlin (NF2) does not bind NEP or its cytosolic region. Using
      experimental data, threading, and sequence analysis, we predicted the involvement
      of moesin residues E(159)Q(160) in binding to the NEP cytosolic domain. Mutation
      of these residues to NL (to mimic the corresponding N(159)L(160) residues in the
      nonbinder merlin) disrupted moesin binding to NEP. Mutation of residues
      N(159)L(160)Y(161)K(162)M(163) in merlin to the corresponding moesin residues
      resulted in NEP binding to merlin. This engineered NEP peptide-merlin interaction
      was diminished by the QNI mutation in NEP, supporting the role of the NEP basic
      cluster in binding. We thus identified the region of interaction between NEP and
      moesin, and engineered merlin into a NEP-binding protein. These data form the
      basis for further exploration of the details of NEP-ERM binding and function.

PMID- 19388050
TI  - Determining protein stability in cell lysates by pulse proteolysis and Western
      blotting.
AB  - Proteins require proper conformational energetics to fold and to function
      correctly. Despite the importance of having information on conformational
      energetics, the investigation of thermodynamic stability has been limited to
      proteins, which can be easily expressed and purified. Many biologically important
      proteins are not suitable for conventional biophysical investigation because of
      the difficulty of expression and purification. As an effort to overcome this
      limitation, we have developed a method to determine the thermodynamic stability
      of low abundant proteins in cell lysates. Previously, it was demonstrated that
      protein stability can be determined quantitatively by measuring the fraction of
      folded proteins with a pulse of proteolysis (Pulse proteolysis). Here, we show
      that thermodynamic stability of low abundant proteins can be determined reliably
      in cell lysates by combining pulse proteolysis with quantitative Western blotting
      (Pulse and Western). To demonstrate the reliability of this method, we determined
      the thermodynamic stability of recombinant human H-ras added to lysates of E.
      coli and human Jurkat T cells. Comparison with the thermodynamic stability
      determined with pure H-ras revealed that Pulse and Western is a reliable way to
      monitor protein stability in cell lysates and the stability of H-ras is not
      affected by other proteins present in cell lysates. This method allows the
      investigation of conformational energetics of proteins in cell lysates without
      cloning, purification, or labeling.

PMID- 19388051
TI  - Thermodynamic characterization of two homologous protein complexes: associations
      of the semaphorin receptor plexin-B1 RhoGTPase binding domain with Rnd1 and
      active Rac1.
AB  - Plexin receptors function in response to semaphorin guidance cues in a variety of
      developmental processes involving cell motility. Interactions with Rho, as well
      as Ras family small GTPases are critical events in the cell signaling mechanism.
      We have recently determined the structure of a cytoplasmic domain (RBD) of plexin
      B1 and mapped its binding interface with several Rho-GTPases, Rac1, Rnd1, and
      RhoD. All three GTPases associate with a similar region of this plexin domain,
      but show different functional behavior in cells. To understand whether
      thermodynamic properties of the GTPase-RBD interaction contribute to such
      different behavior, we have examined the interaction at different temperatures,
      buffer, and pH conditions. Although the binding affinity of both Rnd1 and Rac1
      with the plexin-B1 RBD is similar, the detailed thermodynamic properties of the
      interactions are considerably different. These data suggest that on Rac1 binding
      to the plexin-B1 RBD, the proteins become more rigid in the complex. By contrast,
      Rnd1 binding is consistent with unchanged or slightly increased flexibility in
      one or both proteins. Both GTPases show an appreciable reduction in affinity for
      the dimeric plexin-B1 RBD indicating that GTPase binding is not cooperative with
      dimer formation, but that a partial steric hindrance destabilizes the dimer.
      However, a reduced affinity binding mode to a disulphide stabilized model for the
      dimeric RBD is also possible. Consistent with cellular studies, the interaction
      thermodynamics imply that further levels of regulation involving additional
      binding partners and/or regions outside of the RhoGTPase binding domain are
      required for receptor activation.

PMID- 19388052
TI  - Crystal structures of the Arabidopsis thaliana proliferating cell nuclear antigen
      1 and 2 proteins complexed with the human p21 C-terminal segment.
AB  - The proliferating cell nuclear antigen (PCNA) is well recognized as one of the
      essential cellular components of the DNA replication machinery in all eukaryotic
      organisms. Despite their prominent importance, very little biochemical and
      structural information about plant PCNAs is available, in comparison with that
      obtained from other eukaryotic organisms. We have determined the atomic
      resolution crystal structures of the two distinct Arabidopsis thaliana PCNAs
      (AtPCNA), both complexed with the C-terminal segment of human p21. Both AtPCNAs
      form homotrimeric ring structures, which are essentially identical to each other,
      including the major contacts with the p21 peptide. The structure of the amino
      terminal half of the p21 peptide, containing the typical PIP box sequence, is
      remarkably similar to those observed in the previously reported crystal
      structures of the human and archaeal PCNA-PIP box complexes. Meanwhile, the
      carboxy-terminal halves of the p21 peptide in the plant PCNA complexes are bound
      to the protein in a unique manner, most probably because of crystal packing
      effects. A surface plasmon resonance analysis revealed high affinity between each
      AtPCNA and the C-terminal fragment of human p21. This result strongly suggests
      that the interaction is functionally significant, although no plant homologs of
      p21 have been identified yet. We also discovered that AtPCNA1 and AtPCNA2 form
      heterotrimers, implying that hetero-PCNA rings may play critical roles in
      cellular signal transduction, particularly in DNA repair.

PMID- 19388053
TI  - Recombinant chymosin used for exact and complete removal of a prochymosin derived
      fusion tag releasing intact native target protein.
AB  - Fusion tags add desirable properties to recombinant proteins, but they are not
      necessarily acceptable in the final products. Ideally, fusion tags should be
      removed releasing the intact native protein with no trace of the tag. Unique
      endoproteinases with the ability to cleave outside their own recognition sequence
      can potentially cleave at the boundary of any native protein. Chymosin was
      recently shown to cleave a pro-chymosin derived fusion tag releasing native
      target proteins. In our hands, however, not all proteins are chymosin-resistant
      under the acidic cleavage conditions (pH 4.5) used in this system. Here, we have
      modified the pro-chymosin fusion tag and demonstrated that chymosin can remove
      this tag at more neutral pH (pH 6.2); conditions, that are less prone to
      compromise the integrity of target proteins. Chymosin was successfully used to
      produce intact native target protein both at the level of small and large-scale
      preparations. Using short peptide substrates, we further examined the influence
      of P1' amino acid (the N-terminus of the native target protein) and found that
      chymosin accepts many different, although not all, amino acids. We conclude that
      chymosin has several appealing characteristics for the exact removal of fusion
      tags. It is readily available in highly purified recombinant versions approved by
      the FDA for preparation of food for human consumption. We suggest that one should
      consider extending the use of chymosin to the preparation of pharmaceutical
      proteins.

PMID- 19388056
TI  - Eating disorder behaviors and depression: a minimal relationship beyond social
      comparison, self-esteem, and body dissatisfaction.
AB  - Existing literature fails to comprehensively identify factors contributing to the
      comorbid relationship between eating disorder (ED) behaviors and unipolar
      depression. Maladaptive social comparison, body dissatisfaction, and low self
      esteem are disruptive psychological patterns common to both constructs. It is
      unclear whether a unique relationship exists between depression and eating
      disorder behaviors beyond the effects exerted by this negative cognitive triad.
      The purpose of the present study is to examine whether a unique relationship
      exists between depression and ED behaviors after controlling for maladaptive
      social comparison, body dissatisfaction, and low self-esteem. We predict minimal
      unique variance in ED behaviors will be explained by depression after controlling
      for this negative cognitive triad.

PMID- 19388054
TI  - Active site conformational changes of prostasin provide a new mechanism of
      protease regulation by divalent cations.
AB  - Prostasin or human channel-activating protease 1 has been reported to play a
      critical role in the regulation of extracellular sodium ion transport via its
      activation of the epithelial cell sodium channel. Here, the structure of the
      extracellular portion of the membrane associated serine protease has been solved
      to high resolution in complex with a nonselective d-FFR chloromethyl ketone
      inhibitor, in an apo form, in a form where the apo crystal has been soaked with
      the covalent inhibitor camostat and in complex with the protein inhibitor
      aprotinin. It was also crystallized in the presence of the divalent cation
      Ca(+2). Comparison of the structures with each other and with other members of
      the trypsin-like serine protease family reveals unique structural features of
      prostasin and a large degree of conformational variation within specificity
      determining loops. Of particular interest is the S1 subsite loop which opens and
      closes in response to basic residues or divalent ions, directly binding Ca(+2)
      cations. This induced fit active site provides a new possible mode of regulation
      of trypsin-like proteases adapted in particular to extracellular regions with
      variable ionic concentrations such as the outer membrane layer of the epithelial
      cell.

PMID- 19388055
TI  - Key role of the N-terminus of chicken annexin A5 in vesicle aggregation.
AB  - Annexins are calcium-dependent phospholipid-binding proteins involved in calcium
      signaling and intracellular membrane trafficking among other functions. Vesicle
      aggregation is a crucial event to make possible the membrane remodeling but this
      process is energetically unfavorable, and phospholipid membranes do not aggregate
      and fuse spontaneously. This issue can be circumvented by the presence of
      different agents such as divalent cations and/or proteins, among them some
      annexins. Although human annexin A5 lacks the ability to aggregate vesicles, here
      we demonstrate that its highly similar chicken ortholog induces aggregation of
      vesicles containing acidic phospholipids even at low protein and/or calcium
      concentration by establishment of protein dimers. Our experiments show that the
      ability to aggregate vesicles mainly resides in the N-terminus as truncation of
      the N-terminus of chicken annexin A5 significantly decreases this process and
      replacement of the N-terminus of human annexin A5 by that of chicken switches on
      aggregation; in both cases, there are no changes in the overall protein structure
      and only minor changes in phospholipid binding. Electrostatic repulsions between
      negatively charged residues in the concave face of the molecule, mainly in the N
      terminus, seem to be responsible for the impairment of dimer formation in human
      annexin A5. Taking into account that chicken annexin A5 presents a high sequence
      and structural similarity with mammalian annexins absent in birds, as annexins A3
      and A4, some of the physiological functions exerted by these proteins may be
      carried out by chicken annexin A5, even those that could require calcium
      dependent membrane aggregation.

PMID- 19388057
TI  - A comparison of Latino and Anglo socially desirable responding.
AB  - Previous research suggests that Latinos tend to score higher than Anglos on
      psychometric indicators of socially desirable responding. The purpose of the
      current study was to test several methodological and cultural explanations for
      these group differences. Hypothesized explanations included varying levels of
      problems in living, measurement bias, differential structure of socially
      desirable responding measures, reliabilities of response style indicators, or
      cultural factors. Results supported previous findings that self-identified Latino
      (N=143) respondents score significantly higher than Anglos (N=93) on some
      socially desirable responding indicators. Groups did not differ in levels of
      psychopathology and socially desirable responding indicators demonstrated
      structural similarity, equivalent relations to external criteria, and equivalent
      reliabilities across groups. Thus, data suggest normative differences between
      these groups in social presentation that should be considered in culturally
      sensitive clinical practice.

PMID- 19388058
TI  - Schizotypy, depression, and anxiety in physical and social anhedonia.
AB  - Social anhedonia is a more promising indicator of vulnerability to schizophrenia
      than physical anhedonia, both as assessed by Chapman scales. More broadly, the
      populations identified by these scales would have a propensity to different
      psychiatric disorders. This cross-sectional study examined the respective
      profiles of schizotypy, anxiety, and depression in French students with physical
      and social anhedonia, using psychometric and interview-based measures. Compared
      to controls (n=46), subjects with social anhedonia (n=19) reported higher
      schizotypal scores for interpersonal, paranoid, disorganization, and
      cognitive/perceptual dimensions, whereas subjects with physical anhedonia (n=35)
      had more extensive interpersonal deficits and paranoia. Both groups had more
      depressive and anxiety symptoms than controls, in particular subjects with social
      anhedonia.

PMID- 19388059
TI  - Intrusions related to obsessive-compulsive disorder: a question of content or
      context?
AB  - The aim of the current study was to investigate whether intrusions of individuals
      with obsessive-compulsive disorder (OCD) and nonclinical individuals differed in
      content and in context of occurrence. The results suggest that although the
      intrusions of OCD and nonclinical individuals are similar in content, they differ
      in their context of occurrence. Chi square analyses revealed that the intrusions
      of nonclinical participants were more likely to be directly linked than
      indirectly linked to observations in the here and now, whereas the intrusions of
      participants with OCD were more prone to be indirectly linked than directly
      linked to triggers in the environment at the time they occurred. The implications
      of the results for cognitive models of OCD are discussed.

PMID- 19388060
TI  - Disability and posttraumatic stress disorder in disaster relief workers
      responding to September 11, 2001 World Trade Center disaster.
AB  - Empirical evidence suggests that social and occupational disability plays a
      significant role in posttraumatic stress disorder (PTSD). The purpose of this
      study was to assess the role of social/occupational disability and to identify
      predictors of the development of PTSD in a group of disaster relief workers
      (DRWs) who had been deployed to the World Trade Center (WTC) following September
      11, 2001. Eight hundred forty-two utility workers completed a battery of
      comprehensive tests measuring PTSD and social occupational functioning. Results
      indicated a significant association between PTSD symptoms and impaired
      social/occupational functioning. Symptomatic workers were also more likely to
      have a history of trauma, panic disorder, and depression. Those with a history of
      trauma, depression, generalized anxiety disorder or panic reported significantly
      more disability than those without a psychiatric history. Careful screening of
      PTSD and social/occupational functioning in DRWs following a disaster is
      warranted so that early treatment can be undertaken to prevent a chronic and
      disabling course.

PMID- 19388061
TI  - Mindfulness and experiential avoidance as predictors and outcomes of the
      narrative emotional disclosure task.
AB  - This randomized study examined whether narrative emotional disclosure improves
      mindfulness, experiential avoidance, and mental health, and how baseline levels
      of and changes in mindfulness and experiential avoidance relate to mental health.
      Participants (N=233) wrote repeated traumatic (experimental condition) or
      unemotional daily events narratives (control condition). Regression analyses
      showed neither condition nor gender effects on mental health or experiential
      avoidance at a 1-month follow-up, although the control condition significantly
      increased in one component of mindfulness. Decreased experiential avoidance
      (across conditions) and increased mindfulness (in the experimental condition)
      significantly predicted improved mental health. Narrative disclosure thus did not
      improve outcomes measured here. However, increasing mindfulness when writing
      narratives with traumatic content, and decreasing experiential avoidance
      regardless of writing content, was associated with improved mental health.

PMID- 19388062
TI  - A new narrative for hospitalists.

PMID- 19388063
TI  - BOOSTing the hospital discharge.

PMID- 19388064
TI  - Physical and biophysical effects of polysorbate 20 and 80 on darbepoetin alfa.
AB  - We studied the physical and biophysical affects of the nonionic surfactants
      polysorbate 20 and 80 and their mechanism of interaction using darbepoetin alfa,
      a 4-helix bundle protein, as the exemplary protein. Differences were observed
      between the abilities of the polysorbates to prevent surface loss/aggregation and
      correlated with each polysorbates initiation of micelle formation prior to the
      critical micelle concentration (CMC). The biophysical properties monitored by far
      UV circular dichroism (CD) and tryptophan (Trp) fluorescence showed effects due
      to polysorbates, but were not correlated with their CMC. At a constant protein
      concentration PS-80 induced alpha-helix in the protein with a maximal effect at
      15:1 molar ratio of PS-80/protein. PS-20 initially induced alpha-helix with a
      maximal effect at 1.5:1 ratio followed by a decrease in the alpha-helix content.
      PS-80 had no effect on near-UV CD but increased Trp fluorescence only at the
      150:1 polysorbate/protein ratio. PS-20 decreased the near-UV CD and Trp
      fluorescence. Thermodynamic studies by isothermal titration calorimetry (ITC)
      demonstrated that the protein interacts with monomeric polysorbate, but not with
      polysorbate micelles. The data suggest that the polysorbates differentially
      interact with the protein and that the biophysical effects are dependent on the
      structure of the polysorbate and the polysorbate to protein ratio.

PMID- 19388065
TI  - Discrepancy between admission and discharge diagnoses as a predictor of hospital
      length of stay.
AB  - CONTEXT: The addition of clinical data or present on admission (POA) codes to
      administrative databases improves the accuracy of predicting clinical outcomes,
      such as inpatient mortality. Other POA information may also explain variation in
      hospital outcomes, such as length of stay (LOS), but this potential has not been
      previously explored. OBJECTIVES: To assess whether a discrepancy between the
      diagnosis coded at the time of admission and the diagnoses coded at discharge
      independently explains variation in LOS for general internal medicine patients.
      DESIGN, SETTING, AND PATIENTS: A retrospective data review of patients age 18
      years and older admitted to general internal medicine units at a large, urban
      academic medical center between July 2005 and June 2006. A generalized linear
      regression model was constructed to adjust for patient factors known to be
      associated with LOS. OUTCOME MEASURE: Average LOS among patients with a
      discrepancy between the admitting and discharge diagnosis codes versus those
      patients without a discrepancy. MAIN RESULTS: The average LOS for patients
      without a discrepancy between the admitting and discharge diagnosis codes,
      adjusted for comorbid conditions, was 3.4 days compared to 4.2 days with a
      discrepancy (0.76-day increase; P < 0.01). CONCLUSIONS: Diagnosis discrepancy is
      associated with longer LOS. Diagnosis discrepancy on admission may be a marker of
      diagnosis uncertainty or poor patient assessment/documentation. Further research
      is needed to understand the underlying reasons for this discrepancy and its
      association with LOS, and, potentially, clinical outcomes.

PMID- 19388066
TI  - Risk stratification tools for transient ischemic attack: which patients require
      hospital admission?
AB  - Stroke and transient ischemic attack (TIA) arise from identical etiologies and
      many fatal or disabling strokes are preceded by a TIA. Ten percent of patients
      presenting with a TIA will suffer a stroke within 3 months with half occurring in
      the first 48 hours. Still, many patients with a TIA do not receive timely
      evaluation or therapy. Hospitalization offers the opportunity for rapid
      evaluation and secondary prevention, reduced time to thrombolysis for early
      second strokes, and can be cost effective for high risk patients. Stratification
      tools are now available which allow individualized assessment of risk for early
      second strokes based on patient characteristics on presentation. The use of
      scoring systems such as the ABCD(2) score to predict risk of stroke after TIA are
      useful in making an evidence-based judgment regarding need for hospitalization.
      High-risk patients have an 8.1% risk for stroke in the 48 hours after a TIA and
      warrant hospital admission. Intermediate-risk patients have a 4.1% risk of early
      second stroke and may be considered for admission, observation, or expedited
      clinic evaluation. Low-risk patients have a 2-day stroke risk of only 1% and are
      likely appropriate for prompt outpatient evaluation. TIA is a medical emergency,
      similar to unstable angina, and high risk patients should receive treatment and
      prevention measures instituted with comparable urgency.

PMID- 19388067
TI  - Home alone: assessing mobility independence before discharge.
AB  - Hospitalists are often confronted with discharge planning responsibility and
      decisions for elderly patients who live alone. The absence of an in-home helper
      (spouse, partner, or care-giver) reduces the margin of safety and resilience to
      any new debility. Research has documented that during hospital stays elderly
      patients tend to become deconditioned, even if there is no new specific
      neurologic or motor deficit. In the patient whose pre-hospital mobility
      independence is not robust, and perhaps marginally compensated, inpatient stays
      for any diagnosis may result in critical decrements in mobility independence. The
      present study is an effort to design a bedside tool for the hospitalist by which
      to discern, or screen, for such debility. The tool is a hierarchical performance
      test we named I-MOVE (Independent Mobility Validation Examination). It is a quick
      series of bedside mobility requests to demonstrate capability of fundamental
      movements critical to independent living. We describe manner in which I-MOVE can
      be performed. Moreover, we describe the face validity and the high interrater
      reliability (> 0.90 intra-class correlation coefficient) of two RNs who
      independently administered and scored I-MOVE for 41 patients on a General Medical
      Care Unit. Although not yet studied in correlation with outcomes, nor with
      validated mobility assessment tools, we believe I-MOVE can serve as a useful
      extension of the nurse's assessment, or the Hospitalist's physical examination.
      Discerning the continued capability of mobility independence is a desirable, on
      going insight for discharge planning of the elderly patient who resides alone.

PMID- 19388068
TI  - Rapid response: a quality improvement conundrum.
AB  - Many in-hospital cardiac arrests and other adverse events are heralded by warning
      signs that are evident in the preceding 6 to 8 hours. By promptly intervening
      before further deterioration occurs, rapid response teams (RRTs) are designed to
      decrease unexpected intensive care unit (ICU) transfers, cardiac arrests, and
      inpatient mortality. While implementing RRTs is 1 of the 6 initiatives
      recommended by the Institute for Healthcare Improvement, data supporting their
      effectiveness is equivocal. Before implementing an RRT in our institution, we
      reviewed cases of failure to rescue and found that (1) poor outcomes were often
      associated with attempts to manage early decompensations without a bedside
      evaluation, and (2) the common causes of decompensation for floor patients (early
      sepsis, aspiration, pulmonary embolism) were within the scope of our primary
      teams' practice. Therefore, we felt that prompt, mandatory bedside evaluations by
      the primary team would decrease untoward outcomes.

PMID- 19388069
TI  - The effect of sucrose hydrolysis on the stability of protein therapeutics during
      accelerated formulation studies.
AB  - Stability studies of protein therapeutics are often accelerated by storing
      potential formulations at elevated temperatures where the rates of various
      chemical and physical degradation pathways are increased. An often overlooked
      caveat of using these studies is the potential degradation of the formulation
      components themselves. In this report, we show that the monoclonal antibody
      MAB001 aggregated at a faster rate when formulated with sucrose compared to
      samples that contained sorbitol or no excipient during accelerated stability
      studies following an initial lag phase where the rates of aggregate formation
      were similar in all formulations. The duration of the lag phase was both pH and
      temperature dependent and a significant increase of protein glycation was noticed
      during this time. These observations indicate that the enhanced rate of antibody
      aggregation in sucrose containing formulations is likely due to protein glycation
      following sucrose hydrolysis under accelerated conditions. This hypothesis was
      confirmed by demonstrating that antibody directly glycated with glucose
      aggregated at a faster rate than nonglycated antibody stored in the identical
      formulation. These findings question the utility of using accelerated stability
      data for predicting protein stability in sucrose containing formulations stored
      at 2-8 degrees C, where no glycation or change in aggregation rate was observed.

PMID- 19388070
TI  - Dismantling Rube Goldberg: cutting through chaos to achieve coordinated care.
AB  - Dr. Pham, a practicing general internist and health policy researcher, recalls
      her experience, as a granddaughter, of how patients, families, and physicians are
      often complicit in foiling the good coordination of care.

PMID- 19388072
TI  - Caught in the web: e-diagnosis.

PMID- 19388073
TI  - A 50-year-old man with stage 2 sarcoidosis with pleural involvement.
AB  - We present a case of a 50-year-old man who presented with progressive shortness
      of breath, cough, chest pain, and weight loss. His computer tomography (CT) scan
      of the chest showed a left-sided pleural effusion, subpleural and
      peribronchovascular nodules, bilateral hilar and mediastinal lymphadenopaties.
      Traasbronchial biopsies of the lung parenchyma and Video-Assisted Thoracoscopic
      Surgery (VATS) with pleural biopsies revealed the presence of noncaseating
      granulomas. A diagnosis of stage 2 sarcoidosis with pleural involvement was made
      and treatment with prednisone was started. The patient continued with persistent
      dyspnea and a left-sided pleural effusion. Steroid treatment was tapered and
      leflunomide therapy was initiated. A significant improvement of his clinical
      condition was seen after 1 month on treatment.

PMID- 19388074
TI  - Reduction of 30-day postdischarge hospital readmission or emergency department
      (ED) visit rates in high-risk elderly medical patients through delivery of a
      targeted care bundle.
AB  - RATIONALE: Care coordination has shown inconsistent results as a mechanism to
      reduce hospital readmission and postdischarge emergency department (ED) visit
      rates. OBJECTIVE: To assess the impact of a supplemental care bundle targeting
      high-risk elderly inpatients implemented by hospital-based staff compared to
      usual care on a composite outcome of hospital readmission and/or ED visitation at
      30 and 60 days following discharge. PATIENTS/METHODS: Randomized controlled pilot
      study in 41 medical inpatients predisposed to unplanned readmission or
      postdischarge ED visitation, conducted at Baylor University Medical Center. The
      intervention group care bundle consisted of medication counseling/reconciliation
      by a clinical pharmacist (CP), condition specific education/enhanced discharge
      planning by a care coordinator (CC), and phone follow-up. RESULTS: Groups had
      similar baseline characteristics. Intervention group readmission/ED visit rates
      were reduced at 30 days compared to the control group (10.0% versus 38.1%, P =
      0.04), but not at 60 days (30.0% versus 42.9%, P = 0.52). For those patients who
      had a readmission/postdischarge ED visit, the time interval to this event was
      longer in the intervention group compared to usual care (36.2 versus 15.7 days, P
      = 0.05). Study power was insufficient to reliably compare the effects of the
      intervention on lengths of index hospital stay between groups. CONCLUSIONS: A
      targeted care bundle delivered to high-risk elderly inpatients decreased
      unplanned acute health care utilization up to 30 days following discharge.
      Dissipation of this effect by 60 days postdischarge defines reasonable
      expectations for analogous hospital-based educational interventions. Further
      research is needed regarding the impacts of similar care bundles in larger
      populations across a variety of inpatient settings.

PMID- 19388076
TI  - High-throughput screening of optimal solution conditions for structural
      biological studies by fluorescence correlation spectroscopy.
AB  - Protein aggregation is an essential molecular event in a wide variety of
      biological situations, and is a causal factor in several degenerative diseases.
      The aggregation of proteins also frequently hampers structural biological
      analyses, such as solution NMR studies. Therefore, precise detection and
      characterization of protein aggregation are of crucial importance for various
      research fields. In this study, we demonstrate that fluorescence correlation
      spectroscopy (FCS) using a single-molecule fluorescence detection system enables
      the detection of otherwise invisible aggregation of proteins at higher protein
      concentrations, which are suitable for structural biological experiments, and
      consumes relatively small amounts of protein over a short measurement time.
      Furthermore, utilizing FCS, we established a method for high-throughput screening
      of protein aggregation and optimal solution conditions for structural biological
      experiments.

PMID- 19388075
TI  - Structure of a mutant human purine nucleoside phosphorylase with the prodrug, 2
      fluoro-2'-deoxyadenosine and the cytotoxic drug, 2-fluoroadenine.
AB  - A double mutant of human purine nucleoside phosphorylase (hDM) with the amino
      acid mutations Glu201Gln:Asn243Asp cleaves adenosine-based prodrugs to their
      corresponding cytotoxic drugs. When fused to an anti-tumor targeting component,
      hDM is targeted to tumor cells, where it effectively catalyzes phosphorolysis of
      the prodrug, 2-fluoro-2'-deoxyadenosine (F-dAdo) to the cytotoxic drug, 2
      fluoroadenine (F-Ade). This cytotoxicity should be restricted only to the tumor
      microenvironment, because the endogenously expressed wild type enzyme cannot use
      adenosine-based prodrugs as substrates. To gain insight into the interaction of
      hDM with F-dAdo, we have determined the crystal structures of hDM with F-dAdo and
      F-Ade. The structures reveal that despite the two mutations, the overall fold of
      hDM is nearly identical to the wild type enzyme. Importantly, the residues Gln201
      and Asp243 introduced by the mutation form hydrogen bond contacts with F-dAdo
      that result in its binding and catalysis. Comparison of substrate and product
      complexes suggest that the side chains of Gln201 and Asp243 as well as the purine
      base rotate during catalysis possibly facilitating cleavage of the glycosidic
      bond. The two structures suggest why hDM, unlike the wild-type enzyme, can
      utilize F-dAdo as substrate. More importantly, they provide a critical foundation
      for further optimization of cleavage of adenosine-based prodrugs, such as F-dAdo
      by mutants of human purine nucleoside phosphorylase.

PMID- 19388078
TI  - Major muscle systems in the larval caenogastropod, Ilyanassa obsoleta, display
      different patterns of development.
AB  - This study describes the anatomical and developmental aspects of muscular
      development from the early embryo to competent larval stage in the gastropod
      Ilyanassa obsoleta. Staining of F-actin revealed differential spatial and
      temporal patterns of several muscles. In particular, two major muscles, the
      larval retractor and pedal retractor muscles originate independently and display
      distinct developmental patterns similar to observations in other gastropod
      species. Additionally, together with the larval retractor muscle, the accessory
      larval muscle developed in the embryo at the trochophore stage. Therefore, both
      these muscles develop prior to ontogenetic torsion. The pedal retractor muscle
      marked the most abundant growth in the mid veliger stage. Also during the middle
      stage, the metapodial retractor muscle and opercular retractor muscle grew
      concurrently with development of the foot. We show evidence that juvenile
      muscles, such as the buccal mass muscle and siphon muscle develop initially
      during the late veliger stage. Collectively, these findings substantiate that
      larval myogenesis involves a complex sequence of events that appear evolutionary
      conserved within the gastropods, and set the stage for future studies using this
      model species to address issues concerning the evolution and eventual fates of
      larval musculature in molluscs.

PMID- 19388077
TI  - Selenomethionine incorporation in proteins expressed in Lactococcus lactis.
AB  - Lactococcus lactis is a promising host for (membrane) protein overproduction.
      Here, we describe a protocol for incorporation of selenomethionine (SeMet) into
      proteins expressed in L. lactis. Incorporation efficiencies of SeMet in the
      membrane protein complex OpuA (an ABC transporter) and the soluble protein OppA,
      both from L. lactis, were monitored by mass spectrometry. Both proteins
      incorporated SeMet with high efficiencies (>90%), which greatly extends the
      usefulness of the expression host L. lactis for X-ray crystallography purposes.
      The crystal structure of ligand-free OppA was determined at 2.4 A resolution by a
      semiautomatic approach using selenium single-wavelength anomalous diffraction
      phasing.

PMID- 19388079
TI  - Auxiliary Ca2+ binding sites can influence the structure of CIB1.
AB  - Recent X-ray crystal structures and solution NMR spectroscopy data for calcium-
      and integrin-binding protein 1 (CIB1) have all revealed a common EF-hand domain
      structure for the protein. However, the orientation of the two protein domains,
      the oligomerization state, and the conformations of the N- and C-terminal
      extensions differ among the structures. In this study, we examine whether the
      binding of glutathione or auxiliary Ca(2+) ions as observed in the crystal
      structures, occur in solution, and whether these interactions can influence the
      structure or dimerization of CIB1. In addition, we test the potential phosphatase
      activity of CIB1, which was hypothesized based on the glutathione binding site
      geometry observed in one of the crystal structures of the protein. Biophysical
      and biochemical experiments failed to detect glutathione binding, protein
      dimerization, or phosphatase activity for CIB1 under several solution conditions.
      However, our data identify low affinity (K(d), 10(-2)M) Ca(2+) binding events
      that influence the structures of the N- and C-terminal extensions of CIB1 under
      high (300 mM) Ca(2+) crystallization conditions. In addition to providing a
      rationale for differences amongst the various solution and crystal structures of
      CIB1, our results show that the impact of low affinity Ca(2+) binding events
      should be considered when analyzing and interpreting protein crystallographic
      structures determined in the presence of very high Ca(2+) concentrations.

PMID- 19388080
TI  - Head morphology of the ricefish, Oryzias latipes (Teleostei: Beloniformes).
AB  - The medaka, Oryzias latipes, is a model organism in experimental biology. Its
      ontogeny and osteology have been studied frequently, but no detailed description
      of its cranial anatomy exists. Based on manual dissections, histological slide
      sections, and 3D-reconstructions, we describe the anatomy of the jaw apparatus of
      O. latipes, focusing on musculature, connective tissue elements, and the nervous
      system. The soft tissue anatomy of the head of O. latipes is characterized by
      several derived characters that seem to be related to the modification of the
      upper jaw and a reduced mobility of its bones, which is an evolutionary novelty
      of the Beloniformes. These apomorphies could also be influenced by the small size
      of O. latipes. The maxilla is medial to the premaxilla. The presence of extensive
      connective tissue elements severely limits the mobility of both bones against
      each other and against the neurocranium. The external section of m. adductor
      mandibulae is partly fused with the internal section, originates from the
      quadrate, and inserts to the lower jaw. The intermediate head of the internal
      section is narrow and forms a bend along the ventral margin of the orbit. The
      intramandibular section is a separate narrow muscle between retroarcticular and
      dentary. These characters need to be verified in other representatives of
      Beloniformes to test their contribution to the disputed phylogenetic
      relationships within this taxon and to improve the understanding of the evolution
      of beak-like jaws in beloniform fishes.

PMID- 19388081
TI  - Natural history of late discharges from a general medical ward.
AB  - BACKGROUND: Slow hospital discharges reduce efficiency and compromise care for
      patients awaiting a bed. Although efficient discharge is a widely held goal, the
      natural history of the discharge process has not been well studied. OBJECTIVE: To
      describe the discharge process and identify factors associated with longer and
      later discharges. DESIGN: Prospective cohort study. SETTING: A general medicine
      ward without house-staff coverage, in a tertiary care hospital (The Johns Hopkins
      Hospital) in Baltimore, Maryland, from January 1, 2005 to April 30, 2005.
      PATIENTS: Two hundred and nine consecutively discharged adult inpatients.
      MEASUREMENTS: Discharge time (primary outcome) and discharge duration (secondary
      outcome). RESULTS: Median discharge time was 3:09 PM (25th% to 75th%: 1:08 to
      5:00 PM). In adjusted analysis, discharge time was associated with ambulance used
      on discharge (1.5 hours), prescriptions filled prior to discharge (1.4 hours),
      subspecialty consult prior to discharge (1.2 hours), and procedure prior to
      discharge (1.1 hours). Median duration of the discharge process was 7 hours 34
      minutes (25th% to 75th%: 4.0 to 22.0 hours). Discharge duration was associated
      with discharge to a location other than home (28.9 hours), and with need for
      consultation (14.8 hours) or a procedure (13.4 hours) prior to discharge (all P
      values <0.05). CONCLUSIONS: Discharge time and duration have wide variability.
      Longer and later discharges were associated with procedures and consults.
      Successful efforts to decrease time of discharge will require broad institutional
      effort to improve delivery of interdepartmental services.

PMID- 19388082
TI  - CD-sensitive Zn-porphyrin tweezer host-guest complexes, part 1: MC/OPLS-2005
      computational approach for predicting preferred interporphyrin helicity.
AB  - This article describes a computational study on dimeric zinc porphyrin tweezer
      complexes with primary/secondary amines and secondary alcohols that validates the
      use of Optimized Potential for Liquid Simulations (OPLS-2005) as the lead
      computational choice for assisting the tweezer methodology in the absolute
      configurational assignment of organic compounds. A supramolecular, microscale
      approach known as the tweezer method has been widely applied in the past decade
      for determining the absolute configuration of chiral substrates that are
      difficult to study by other readily available methods. The method relies on a
      host/guest complexation mechanism between a porphyrin tweezer moiety and a
      substrate, after its conversion into a bidentate conjugate. The formation of 1:1
      complexes is a stereodifferentiating process: upon complexation, the originally
      achiral tweezer adopts a preferential interporphyrin helicity, dictated by the
      absolute configuration of the chiral substrate. By correctly predicting the sign
      of the interporphyrin helicity in the complex, OPLS-2005 provides a correlation
      between the observed circular dichroism (CD) signal and the absolute
      configuration of the substrate. It also offers a great degree of insight into the
      structural factors responsible for chiral recognition and the amplitude of
      exciton couplets. Moreover, the preferential binding sites between the Zn-tweezer
      and secondary amine conjugates were revealed by using the new computational
      approach.

PMID- 19388083
TI  - CD-sensitive Zn-porphyrin tweezer host-guest complexes, part 2: cis- and trans-3
      hydroxy-4-aryl/alkyl-beta-lactams. A case study.
AB  - This article describes an application of the host-guest chiral recognition
      approach called tweezer methodology for the determination of the absolute
      configuration of 3-hydroxy-beta-lactams. These substrates represent challenging
      cases due to their chemical reactivity, the presence of multiple stereogenic
      centers and several functional groups which offer various possibilities of
      binding to the Zn-porphyrin host. OPLS-2005, the force field used in this work to
      predict the interporphyrin twist, modeled correctly the host-guest complexation
      mechanism and revealed conformational details of the bound substrates. The
      computational study also suggested that in cases where an increase in the
      magnitude of the stereodifferentiation and an intense experimental CD are
      observed, the bound conformation of the conjugates are hydrogen bonded. The
      present investigation provides evidence that when the tweezer method is assisted
      by the OPLS-2005 based computational approach, it can be successfully applied to
      the configurational and conformational elucidation of multi-functional compounds
      with multiple stereogenic centers.

PMID- 19388084
TI  - Smad2/3 is involved in growth inhibition of mouse embryonic palate mesenchymal
      cells induced by all-trans retinoic acid.
AB  - BACKGROUND: Cleft palate is one of the major malformations induced by retinoic
      acid in both rodents and humans. The purpose of the present study was to
      elucidate the mechanism by which all-trans retinoic acid (atRA) induces the cleft
      palate. METHODS: The cell cycle distribution of mouse embryonic palate
      mesenchymal (MEPM) cells under atRA (100 mg/kg) treatment on gestation day (GD)
      10 or GD 12 were measured by immunohistochemistry and flow cytometry. The p21,
      phospho-Rb, Smad2/3, phospho-Smad2 and phospho-Smad3 protein expression levels
      were detected by western blot, respectively. Quantitative real-time PCR was
      performed for p21, Smad2, and Smad3 gene expression in each group under both
      conditions. Small interfering RNA (siRNA) was applied to inhibit Smad2/3
      expression in MEPM cells and the effect was detected by western blot and flow
      cytometry. RESULTS: The G(0)/G(1) arrest in MEPM cells in vivo was induced by
      atRA on GD 10. The protein expression levels of p21, Smad2/3, phospho-Smad2, and
      phospho-Smad3 were increased, while phospho-Rb was decreased in MEPM after atRA
      treatment on GD 10. These changes were not observed on the GD 12 group. Moreover,
      the mRNA expression levels of p21, Smad2, and Smad3 detected by quantitative real
      time PCR were almost consistent with their protein expression trends.
      Furthermore, p21 was partially decreased and G(0)/G(1) arrest was partially
      released following Smad2/3 siRNA knockdown. CONCLUSIONS: The induction of
      G(0)/G(1) block by atRA in MEPM cells varied with the development stage of
      exposure. Our study demonstrated that Smad2/3 regulation of p21 was partly
      required for atRA-induced cell cycle perturbations in MEPM cells.

PMID- 19388085
TI  - Fast identification of thermostable beta-glucosidase mutants on cellobiose by a
      novel combinatorial selection/screening approach.
AB  - Engineering costly cellulases on natural cellulosic substrates is of importance
      for emerging biomass-based biorefineries. Directed enzyme evolution is becoming a
      popular tool, but identification of desired mutants from a large mutant library
      remains challenging sometimes. In this work, we demonstrated a novel
      combinatorial selection/screening strategy for finding thermostable beta
      glucosidase on its natural substrate-cellobiose. First, selection was conducted
      through complementation of beta-glucosidase for non-cellobiose-utilizing
      Escherichia coli so that only the cells expressing active beta-glucosidase can
      grow on a M9 synthetic medium with cellobiose as the sole carbon source
      (selection plate). Second, the clones on the selection plates were duplicated by
      using nylon membranes. After heat treatment, the nylon membranes were overlaid on
      M9/cellobiose screening plates so that remaining activities of thermostable beta
      glucosidase mutants hydrolyzed cellobiose on the screening plates to glucose.
      Third, the growth of an indicator E. coli strain that can utilize glucose but not
      cellobiose on the screening plates helped detect the thermostable beta
      glucosidase mutants on the selection plates. Several thermostable mutants were
      identified from a random mutant library of the Paenibacillus polymyxa beta
      glucosidase. The most thermostable mutant A17S had an 11-fold increase in the
      half-life of thermoinactivation at 50 degrees C.

PMID- 19388086
TI  - Quantitative inference of cellular parameters from microfluidic cell culture
      systems.
AB  - Microfluidic cell culture systems offer a convenient way to measure cell
      biophysical parameters in conditions close to the physiological environment. We
      demonstrate the application of a mathematical model describing the spatial
      distribution of nutrient and growth factor concentrations in inferring cellular
      oxygen uptake rates from experimental measurements. We use experimental
      measurements of oxygen concentrations in a poly(dimethylsiloxane) (PDMS)
      microreactor culturing human hepatocellular liver carcinoma cells (HepG2) to
      infer quantitative information on cellular oxygen uptake rates. We use a novel
      microchannel design to avoid the parameter correlation problem associated with
      simultaneous cellular uptake and diffusion of oxygen through the PDMS surface. We
      find that the cellular uptake of oxygen is dependent on the cell density and can
      be modeled using a logistic term in the Michaelis-Menten equation. Our results
      are significant not only for the development of novel assays to quantitatively
      infer cell response to stimuli, but also for the development, design, and
      optimization of novel in vitro systems for drug discovery and tissue engineering.

PMID- 19388087
TI  - High-resolution (1)H NMR investigations of the capacity of dentifrices containing
      a "smart" bioactive glass to influence the metabolic profile of and deliver
      calcium ions to human saliva.
AB  - Dentifrices containing H(2)O-reactive bioactive glasses alleviate
      hypersensitivity in teeth via the blockage of open dentinal tubules. Here, the
      ability of two such products to release Ca(2+) ions into human saliva was
      investigated, together with their influence on the status of this biofluid's (1)H
      NMR-detectable biomolecules. Human salivary supernatants were equilibrated with
      increasing volumes of those derived from each dentifrice (5.00 min at 37 degrees
      C). These biofluids were also equilibrated at 37 degrees C with a preselected
      quantity of the intact products (samples were collected at increasing
      timepoints). Salivary Ca(2+) concentrations were monitored by a (1)H NMR
      technique involving ethylenediamine tetra-acetate addition and/or atomic
      absorption spectrometry. Added Ca(2+)- and dentifrice supernatant volume (DSV)
      induced modifications to the salivary (1)H NMR profile were explored by spectral
      titration. Data acquired demonstrated added DSV-dependent increases in salivary
      Ca(2+) concentrations and (Ca(2+)-independent) modifications to the intensities
      of selected salivary (1)H NMR signals, particularly those of the malodorous
      amines methyl-, dimethyl-, and trimethylamines, which were diminished by up to
      80% of their prior values. Time-dependent elevations in salivary Ca(2+) level
      were observed on equilibration with the intact dentifrices. Added Ca(2+) ions
      exerted a concentration-dependent influence on a range of resonances (including
      those of citrate, succinate, pyruvate, and lactate). These data provide valuable
      information regarding the mechanisms of action of the products tested.

PMID- 19388088
TI  - In vivo and in vitro evaluation of gelation and hemostatic properties of a novel
      tissue-adhesive hydrogel containing a cross-linkable polymeric micelle.
AB  - There is a clinical requirement for a local hemostat that arrests bleeding from
      both suture holes and cross-sectional surfaces of parenchymatous organs. A novel
      tissue-adhesive hydrogel was prepared that contains a cross-linkable polymeric
      micelle consisting of poly(ethylene glycol)-poly(DL-lactide) block polymers, and,
      by means of a rheometer, the factors that affect the hydrogel's gelation
      properties was clarified. The storage modulus and the gelation time greatly
      depended on both the pH and the concentrations of both the polymeric micelle and
      polyallylamine solutions. Furthermore, the hemostatic potential of the hydrogel
      in a mouse hemostasis model was evaluated under optimal conditions as determined
      by the rheometer. The average amount of bleeding from the mouse liver was 172.9
      mg (S.D. 69.7 mg, N = 7) in the control experiments, whereas it was 20.1 mg (s.d.
      13.2, N = 7) when the hydrogel was applied to the wound (p = 0.002). The result
      demonstrated that the novel synthetic hydrogel possessed a significant hemostatic
      potential as a local hemostat.

PMID- 19388089
TI  - Urethane dimethacrylate: a molecule that may cause confusion in dental research.
AB  - In recent years, the elution of monomers from dental materials has been a cause
      for public concern. Urethane dimethacrylate, commonly abbreviated to UDMA, is one
      of the monomers that are most often tested with regard to elution from and
      cytotoxicity of resin-based materials. Although each chemical name represents the
      chemical type, chemical structure, and molecular weight of a molecule, it does
      not seem to be the same with UDMA. In the present paper, the different forms of
      UDMA are presented. These include those used by dental manufacturers to produce
      composite materials and the different types of urethane dimethacrylate used in
      studies concerning the elution of monomers from composite materials. High
      performance liquid chromatography (HPLC) is usually used to detect the eluted
      monomers, but it does not appear to be adequate in determining the different
      forms of UDMA. The combination of HPLC with mass spectrometry is shown to be able
      to specifically identify the compounds eluted in addition to those compounds used
      as standards in the various studies. The fact that the same name is given to
      different molecules causes confusion about the results of studies testing the
      elusion of monomers from composite materials and their possible toxicity.

PMID- 19388090
TI  - RGD modified PLGA/gelatin microspheres as microcarriers for chondrocyte delivery.
AB  - Poly(lactide-co-glycotide) (PLGA)/gelatin composite microspheres were prepared by
      an emulsion solvent evaporation technique. RGDS peptides were further immobilized
      under the catalyzation of water soluble carbodiimide (EDAC). Confocal laser
      scanning microscopy and transmission electron microscopy revealed that the
      gelatin was entrapped in the PLGA/gelatin microspheres with a manner of separated
      domains. The contents of the entrapped gelatin and immobilized RGDS peptides were
      quantified as 0.9 mg/20 mg and approximately 2.1 microg/20 mg microspheres by
      hydroxyproline analysis and bicinchoninic acid protein assay, respectively.
      Moreover, difference in morphology of PLGA, PLGA/gelatin and RGDS modified
      PLGA/gelatin (PLGA/gelatin-RGDS) microspheres was observed by scanning electron
      microscopy. The PLGA/gelatin and PLGA/gelatin-RGDS microspheres lost their weight
      rapidly in PBS, but slowly in DMEM/fetal bovine serum. Rabbit auricular
      chondrocytes were seeded onto the microspheres in vitro to assess their
      biological performance and applicability as cell carriers. Results show that
      amongst the PLGA, PLGA/gelatin and PLGA/gelatin-RGDS microspheres, the latter
      ones have the best performance in terms of chondrocyte attachment, proliferation,
      viability and sulfated glycosaminoglycans secretion.

PMID- 19388091
TI  - Pseudoplasticity and setting properties of two-solution bone cement containing
      poly(methyl methacrylate) microspheres and nanospheres for kyphoplasty and
      vertebroplasty.
AB  - The viscosity and setting parameters of acrylic bone cements used for restoring
      vertebral compression fractures are critical factors in vertebroplasty and
      kyphoplasty procedures. Cements exhibiting lower viscosities and longer setting
      times are desired to overcome the difficulty of forcing the dough through small
      gauge needles and to reduce the risk of cementing them during surgery. However,
      cement extravasation is of great concern and can result when cements exhibiting
      lower viscosities are used. Therefore, the viscosity of cements should also be
      highly pseudoplastic to simultaneously facilitate flow through needles (shear
      thinning) and inhibit potentially deleterious extravasation by viscosity recovery
      at the delivery sites. The viscosity of two-solution bone cement can be
      manipulated by changes in the polymer-to-monomer ratio and by the incorporation
      of cross-linked poly(methyl methacrylate), (PMMA), microspheres or nanospheres in
      the polymer phase. In this study, the effect of the addition of cross-linked PMMA
      particles to the linear polymer-monomer solution with particle sizes ranging from
      20-100 microm (microspheres) and 300-330 nm (nanospheres) is evaluated in terms
      of cement rheological properties and setting behavior. The addition of cross
      linked PMMA particles was observed to reduce the viscosity in comparison to the
      standard formulation while keeping the pseudoplastic characteristics, and to
      improve the setting properties by increasing curing time and reducing maximum
      exotherm significantly.

PMID- 19388092
TI  - In vitro adherence of oral streptococci to zirconia core and veneering glass
      ceramics.
AB  - Plaque formation on dental ceramics may cause gingival inflammation and secondary
      caries. This in vitro study compared the susceptibility of various dental
      ceramics to adhere oral streptococci, and verified the influence of substratum
      surface roughness and surface hydrophobicity. Three zirconia ceramic materials
      and three veneering glass-ceramics were investigated. Fifteen test specimens were
      prepared for each material, polished, and surface roughness and hydrophobicity
      were determined. After incubation with artificial saliva (2 h, 37 degrees C) for
      pellicle formation, specimens were incubated with suspensions of Streptococcus
      gordonii DSMZ 6777, Streptococcus mutans DSMZ 20523, Streptococcus oralis DSMZ
      20627, or Streptococcus sanguinis DSMZ 20068, respectively, for 2.5 h at 37
      degrees C. Adherent bacteria were quantified using a fluorescence dye for viable
      cell quantification (Alamar Blue/Resazurin). Statistical analysis was performed
      using one- and two-way ANOVA and the Tukey-Kramer multiple comparison test for
      post hoc analysis (alpha < 0.05). Surface roughness and surface hydrophobicity
      differed significantly among the various ceramics; protein coating hydrophilized
      the surfaces, and led to a homogenization of the surface hydrophobicity of the
      various ceramics. Before protein coating, almost similar relative fluorescence
      intensities indicating similar adhesion of streptococci were found for the
      various ceramics; more distinct differences were observed after protein coating.
      Correlations between surface parameters and streptococcal adhesion were poor.
      Within the limitations of these experiments, the findings of this in vitro study
      indicate only little differences between zirconia and glass ceramic with regard
      to streptococcal adhesion. Judging from these results, it is unlikely that
      exposed zirconia surfaces yield more plaque than glass ceramic surfaces in vivo.

PMID- 19388093
TI  - Conditions affecting cell seeding onto three-dimensional scaffolds for cellular
      based biodegradable implants.
AB  - Seeding cells efficiently and uniformly onto three-dimensional scaffolds is a key
      element for engineering tissues, particularly when only a low-number of cells is
      available for tissue repair and regeneration. The aim of this study was to
      evaluate three seeding techniques on two biocompatible scaffolds in vitro using
      chondrocytes as follows: (1) static; (2) modified centrifugal cell immobilization
      (CCI); and (3) dynamic oscillating motion. Five milliliters of media containing
      5, 10, or 25 million articular, auricular, or costal chondrocytes were used to
      seed porous PLGA scaffolds and sections of devitalized cartilage. The dynamic
      oscillating technique resulted in up to 150% higher cellular load at 7 days than
      CCI seeding. Cell distribution was more homogeneous throughout the scaffold under
      dynamic conditions versus more sporadic and dispersed cell concentrations on the
      scaffolds when using either the static or the modified CCI technique. Cell load
      and distribution, when using a low numbers of chondrocytes at one and two million
      cells per milliliter, was comparable to that using the much higher number,
      especially under dynamic seeding conditions. The seeded scaffolds were used as
      implants to achieve cellular bonding between two devitalized meniscus discs. The
      constructs were implanted subcutaneously in nude mice for 12 weeks and analyzed
      histologically. Implants seeded with auricular chondrocytes showed qualitative
      more integration into native meniscus tissue than articular and costal cell
      implants. We conclude the dynamic oscillating seeding technique is an efficient
      technique for seeding low-cell numbers onto scaffolds resulting in consistent and
      uniform cell distribution throughout porous PLGA scaffolds.

PMID- 19388094
TI  - MRI of late microstructural and metabolic alterations in radiation-induced brain
      injuries.
AB  - PURPOSE: To evaluate the late effects of radiation-induced damages in the rat
      brain by means of in vivo multiparametric MRI. MATERIALS AND METHODS: The right
      hemibrains of seven Sprague-Dawley rats were irradiated with a highly collimated
      6 MV photon beam at a single dose of approximately 28 Gy. Diffusion tensor
      imaging (DTI), proton MR spectroscopy ((1)H-MRS), T2-weighted imaging, and T1
      weighted imaging were performed to the same animals 12 months after radiation
      treatment. RESULTS: Compared with the contralateral side, a significantly higher
      percentage decrease in fractional anisotropy was observed in the ipsilateral
      fimbria of hippocampus (29%) than the external capsule (8%) in DTI, indicating
      the selective vulnerability of fimbria to radiation treatment. Furthermore, in
      (1)H-MRS, significantly higher choline, glutamate, lactate, and taurine peaks by
      24%, 25%, 87%, and 58%, respectively, were observed relative to creatine in the
      ipsilateral brain. Postmortem histology confirmed these white matter degradations
      as well as glial fibrillary acidic protein and glutamine synthetase
      immunoreactivity increase in the ipsilateral brain. CONCLUSION: The
      microstructural and metabolic changes in late radiation-induced brain injuries
      were documented in vivo. These multiparametric MRI measurements may help
      understand the white matter changes and neurotoxicity upon radiation treatment in
      a single setting.

PMID- 19388095
TI  - MRI and histological analysis of beta-amyloid plaques in both human Alzheimer's
      disease and APP/PS1 transgenic mice.
AB  - PURPOSE: To investigate the relationship between MR image contrast associated
      with beta-amyloid (Abeta) plaques and their histology and compare the
      histopathological basis of image contrast and the relaxation mechanism associated
      with Abeta plaques in human Alzheimer's disease (AD) and transgenic APP/PS1 mouse
      tissues. MATERIALS AND METHODS: With the aid of the previously developed
      histological coil, T(2) (*)-weighted images and R(2) (*) parametric maps were
      directly compared with histology stains acquired from the same set of Alzheimer's
      and APP/PS1 tissue slices. RESULTS: The electron microscopy and histology images
      revealed significant differences in plaque morphology and associated iron
      concentration between AD and transgenic APP/PS1 mice tissue samples. For AD
      tissues, T(2) (*) contrast of Abeta-plaques was directly associated with the
      gradation of iron concentration. Plaques with significantly less iron load in the
      APP/PS1 animal tissues are equally conspicuous as the human plaques in the MR
      images. CONCLUSION: These data suggest a duality in the relaxation mechanism
      where both high focal iron concentration and highly compact fibrillar beta
      amyloid masses cause rapid proton transverse magnetization decay. For human
      tissues, the former mechanism is likely the dominant source of R(2) (*)
      relaxation; for APP/PS1 animals, the latter is likely the major cause of
      increased transverse proton relaxation rate in Abeta plaques. The data presented
      are essential for understanding the histopathological underpinning of MRI
      measurement associated with Abeta plaques in humans and animals.

PMID- 19388098
TI  - Comparison of spiral imaging and SENSE-EPI at 1.5 and 3.0 T using a controlled
      cerebrovascular challenge.
AB  - PURPOSE: To quantitatively compare spiral imaging and sensitivity-encoded-echo
      planar-imaging (SENSE-EPI) methods for blood oxygen level-dependent (BOLD)
      imaging using controlled changes in the end-tidal partial pressure of CO(2)
      (PetCO(2)) to provide a global BOLD response. Specifically, we examined
      susceptibility-field-gradient effects on the BOLD sensitivity throughout the
      brain. MATERIALS AND METHODS: We quantified cerebrovascular reactivity (CVR)
      using the BOLD response to cyclic changes in PetCO(2) in five healthy volunteers
      at 1.5 and 3.0 T using spiral imaging and SENSE-EPI. We compared the two
      techniques with respect to susceptibility-induced signal dropout and CVR t
      statistic. RESULTS: Compared to spiral imaging, SENSE-EPI significantly reduced
      the volume of signal dropout by 32 +/- 18% at 3.0 T. In regions with large
      susceptibility gradients, SENSE-EPI demonstrated a trend for a greater t
      statistic than spiral imaging, particularly at 3.0 T. However, no statistically
      significant between-technique differences existed. CONCLUSION: The results at 3.0
      T suggest that, compared with spiral imaging, SENSE-EPI reduces signal loss
      associated with susceptibility field gradients in affected regions without
      affecting BOLD sensitivity. This study also demonstrates a unique application of
      controlled PetCO(2) changes to quantitatively compare BOLD techniques, which may
      be useful for the design of future fMRI studies.

PMID- 19388096
TI  - Early marker for Alzheimer's disease: hippocampus T1rho (T(1rho)) estimation.
AB  - PURPOSE: To evaluate the T1rho (T(1rho)) MRI relaxation time in hippocampus in
      the brain of Alzheimer's disease (AD), mild cognitive impairment (MCI), and
      control, and to determine whether the T(1rho) shows any significant difference
      between these cohorts. MATERIALS AND METHODS: With informed consent, AD (n = 49),
      MCI (n = 48), and age-matched control (n = 31) underwent T(1rho) MRI on a Siemens
      1.5T Scanner. T(1rho) values were automatically calculated from the left and
      right hippocampus region using in-house developed software. Bonferroni post-hoc
      multiple comparisons was performed to compare the T(1rho) value among the
      different cohorts. RESULTS: Significantly higher T(1rho) values were observed
      both in AD (P = 0.000) and MCI (P = 0.037) cohorts compared to control; also, the
      T(1rho) in AD was significantly high over (P = 0.032) MCI. Hippocampus T(1rho)
      was 13% greater in the AD patients than control, while in MCI it was 7% greater
      than control. Hippocampus T(1rho) in AD patients was 6% greater than MCI.
      CONCLUSION: Higher hippocampus T(1rho) values in the AD patients might be
      associated with the increased plaques burden. A follow-up study would help to
      determine the efficacy of T(1rho) values as a predictor of developing AD in the
      control and MCI individuals.

PMID- 19388099
TI  - Image artifacts in concurrent transcranial magnetic stimulation (TMS) and fMRI
      caused by leakage currents: modeling and compensation.
AB  - PURPOSE: To characterize and eliminate a new type of image artifact in concurrent
      transcranial magnetic stimulation and functional MRI (TMS-fMRI) caused by small
      leakage currents originating from the high-voltage capacitors in the TMS
      stimulator system. MATERIALS AND METHODS: The artifacts in echo-planar images
      (EPI) caused by leakage currents were characterized and quantified in numerical
      simulations and phantom studies with different phantom-coil geometries. A relay
      diode combination was devised and inserted in the TMS circuit that shorts the
      leakage current. Its effectiveness for artifact reduction was assessed in a
      phantom scan resembling a realistic TMS-fMRI experiment. RESULTS: The leakage
      current-induced signal changes exhibited a multipolar spatial pattern and the
      maxima exceeded 1% at realistic coil-cortex distances. The relay-diode
      combination effectively reduced the artifact to a negligible level. CONCLUSION:
      The leakage-current artifacts potentially obscure effects of interest or lead to
      false-positives. Since the artifact depends on the experimental setup and design
      (eg, amplitude of the leakage current, coil orientation, paradigm, EPI
      parameters), we recommend its assessment for each experiment. The relay-diode
      combination can eliminate the artifacts if necessary.

PMID- 19388100
TI  - Effect of flip angle on volume flow measurement with nontriggered phase-contrast
      MR: In vivo evaluation in carotid and basilar arteries.
AB  - PURPOSE: To evaluate the effect of flip angle on volume flow rate measurements
      obtained with nontriggered phase-contrast magnetic resonance imaging (MRI) in
      vivo. MATERIALS AND METHODS: We prospectively measured volume flow rates of the
      bilateral internal carotid artery and the basilar artery with cine and
      nontriggered phase-contrast MRI. For nontriggered phase-contrast imaging, flip
      angles of 4, 15, 60, and 90 degrees were used for 40 volunteers and of 8, 15, and
      30 degrees for 54 volunteers. Lumen boundaries were semiautomatically determined
      by pulsatility-based segmentation using cine phase-contrast MRI. Identical lumen
      boundaries were used for nontriggered phase-contrast imaging. RESULTS: The ratio
      of volume flow rate obtained with nontriggered phase-contrast imaging to that
      obtained with cine phase-contrast imaging significantly increases with an
      increase in the flip angle. The mean ratios lie within a relatively narrow range
      of +/-15% with a wide range of flip angles of 8-90 degrees . As the flip angle
      increases, ghost artifacts become prominent and signal-to-noise and contrast-to
      noise ratios increase. CONCLUSION: Flip angles between 8 and 60 degrees are most
      appropriate for nontriggered phase-contrast MR measurements in the internal
      carotid and the basilar artery.

PMID- 19388101
TI  - Evaluation of intraportal venous flow distribution by unenhanced MR angiography
      using three-dimensional fast spin-echo with a selective tagging pulse: efficacy
      of subtraction of tag-on and tag-off images acquired during a single breath-hold.
AB  - PURPOSE: To evaluate the efficacy of subtracted MR images from two sets of
      unenhanced three-dimensional (3D) MR angiography data (tag-on and tag-off images)
      acquired simultaneously during a single breath-hold in assessing the intraportal
      venous flow distribution to the distal branches from the superior mesenteric vein
      (SMV) and the splenic vein (SpV). MATERIALS AND METHODS: Tag-on and tag-off MR
      images during a single breath-hold were obtained in 25 normal subjects. Tagging
      pulse was placed on the SMV or SpV separately to study inflow correlation of
      tagged blood into the portal vein. RESULTS: On the MR images tagged on the SMV,
      the mean ratings of visibility of tagged blood flow on the subtracted images were
      significantly higher (P = 0.016-0.0001) than those on the source images in almost
      all branches except second-ordered left portal vein (P = 0.096). On the
      subtracted MR images tagged on SMV, the tramline (16 of the 25 subjects) was the
      most common distribution pattern of the tagged blood inflow in the main portal
      vein. CONCLUSION: Subtracted MR images from two sets of unenhanced 3D MR
      angiography data (tag-on and tag-off images) acquired simultaneously would be
      effective to show the blood flow distribution of tagged blood into the portal
      vein and distal branches from SMV and SpV under the physiological condition
      without contrast injections.

PMID- 19388102
TI  - Slice offset frequency and shim adjustment for interactive steady-state free
      precession (SSFP) imaging.
AB  - PURPOSE: To devise a method allowing real-time optimization of center frequency
      (CF) and shim for an interactive steady-state free-precession (SSFP) sequence by
      reformatting a previously acquired field map in the same orientation as the
      interactive acquisition. MATERIALS AND METHODS: Field maps were acquired in a
      rectangular parallel-piped phantom and a normal volunteer. An SSFP sequence was
      modified to communicate the current slice offset and rotation to an external
      program that reformatted the field map into the same plane, calculated the CF and
      shim offsets, and passed them back to the sequence. CF offsets as a function of
      position for the phantom were compared with the scanner prescan-determined
      offset. RESULTS: In the phantom, the CF measurements agreed with the scanner
      determined offsets. Bland-Altman analysis showed a bias of -14 Hz (field map -
      prescan) and limits of agreement of -28 to 0 Hz. In the volunteer there was a
      qualitative improvement in image quality when using the optimized center
      frequencies and shims. CONCLUSION: The proposed method demonstrates how CF and
      shim can be optimized for any interactively positioned slice, resulting in
      reduced off-resonance artifacts.

PMID- 19388103
TI  - Signal fluctuations induced by non-T1-related confounds in variable TR fMRI
      experiments.
AB  - PURPOSE: To assess and model signal fluctuations induced by non-T(1)-related
      confounds in variable repetition time (TR) functional magnetic resonance imaging
      (fMRI) and to develop a compensation procedure to correct for the non-T(1)
      related artifacts. MATERIALS AND METHODS: Radiofrequency disabled volume gradient
      sequences were effected at variable offsets between actual image acquisitions,
      enabling perturbation of the measurement system without perturbing longitudinal
      magnetization, allowing the study of non-T(1)-related confounds that may arise in
      variable TR experiments. Three imaging sessions utilizing a daily quality
      assurance (DQA) phantom were conducted to assess the signal fluctuations, which
      were then modeled as a second-order system. A modified projection procedure was
      implemented to correct for signal fluctuations arising from non-T(1)-related
      confounds, and statistical analysis was performed to assess the significance of
      the artifacts with and without compensation. RESULTS: Assessment using phantom
      data reveals that the signal fluctuations induced by non-T(1)-related confounds
      was consistent in shape across the phantom and well-modeled by a second-order
      system. The phantom exhibited significant spurious detections (at P < 0.01)
      almost uniformly across the central slices of the phantom. CONCLUSION: Second
      order system modeling and compensation of non-T(1)-related confounds achieves
      significant reduction of spurious detection of fMRI activity in a phantom.

PMID- 19388104
TI  - Nephrogenic systemic fibrosis: the need for accurate case reporting.

PMID- 19388106
TI  - Halting the effects of flow enhancement with effective intermittent
      zeugmatographic encoding (HEFEWEIZEN) in SSFP.
AB  - PURPOSE: To describe a new method for performing dark blood (DB) magnetization
      preparation in TrueFISP (bSSFP) and apply the technique to high-resolution
      carotid artery imaging. MATERIALS AND METHODS: The developed method (HEFEWEIZEN)
      provides directional flow suppression, while preserving bSSFP contrast, by
      periodically applying spatial saturation in short repetition time (TR) TrueFISP.
      Steady-state free precession (SSFP) conditions are maintained throughout the
      acquisition for the imaging slice magnetization. HEFEWEIZEN was implemented on a
      1.5 T scanner with standard receiver coils. Studies were performed in phantoms,
      eight asymptomatic volunteers, and two patients with low- and high-grade carotid
      artery stenosis. RESULTS: Average flow suppression was 88% +/- 4% (arterial) and
      85% +/- 3% (venous) in a multislice study. Stationary signal, contrast, and fine
      details were maintained with only slight signal suppression (11% +/- 11%).
      Comparison to diffusion-prepared SSFP in the common carotid artery demonstrated
      significant improvement in wall-lumen contrast-to-noise ratio efficiency (P =
      0.024). DB contrast was achieved with only 13% increased acquisition time (14.3
      sec). Further acceleration was possible by confining the DB preparation to the
      central 60% of k-space. CONCLUSION: A fast, short TR, DB TrueFISP pulse sequence
      was developed and tested in the carotid arteries of asymptomatic volunteers and
      patients.

PMID- 19388107
TI  - 3D diffusion tensor MRI with isotropic resolution using a steady-state radial
      acquisition.
AB  - PURPOSE: To obtain diffusion tensor images (DTI) over a large image volume
      rapidly with 3D isotropic spatial resolution, minimal spatial distortions, and
      reduced motion artifacts, a diffusion-weighted steady-state 3D projection (SS
      3DPR) pulse sequence was developed. MATERIALS AND METHODS: A diffusion gradient
      was inserted in a SS 3DPR pulse sequence. The acquisition was synchronized to the
      cardiac cycle, linear phase errors were corrected along the readout direction,
      and each projection was weighted by measures of consistency with other data. A
      new iterative parallel imaging reconstruction method was also implemented for
      removing off-resonance and undersampling artifacts simultaneously. RESULTS: The
      contrast and appearance of both the fractional anisotropy and eigenvector color
      maps were substantially improved after all correction techniques were applied.
      True 3D DTI datasets were obtained in vivo over the whole brain (240 mm field of
      view in all directions) with 1.87 mm isotropic spatial resolution, six diffusion
      encoding directions in under 19 minutes. CONCLUSION: A true 3D DTI pulse sequence
      with high isotropic spatial resolution was developed for whole brain imaging in
      under 20 minutes. To minimize the effects of brain motion, a cardiac
      synchronized, multiecho, DW-SSFP pulse sequence was implemented. Motion artifacts
      were further reduced by a combination of linear phase correction, corrupt
      projection detection and rejection, sampling density reweighting, and parallel
      imaging reconstruction. The combination of these methods greatly improved the
      quality of 3D DTI in the brain.

PMID- 19388108
TI  - MR imaging findings of small bowel hemorrhage: two cases of mural involvement and
      one of perimural.
AB  - PURPOSE: To demonstrate the MR appearance of small bowel wall hemorrhage.
      MATERIALS AND METHODS: A search was performed of the clinical information system
      (CIS) and the abdominal MRI databases of our institution for patients diagnosed
      with bowel hemorrhage on MRI between January 1, 2000, and July 31, 2008. All
      patients were imaged using a protocol that included noncontrast T1- and T2
      weighted images and postgadolinium gradient echo images. RESULTS: Two male
      patients, 44 and 55 years of age, were identified with small bowel mural
      hemorrhage, one in the duodenum and one in the jejunum. A third patient, a 66
      year-old man, was identified with perimural hematoma. The following imaging
      features were observed: for mural hemorrhage, mural-based increased signal
      intensity (SI) in the bowel wall on fat suppressed T1-weighted images, variable
      increased SI on T2-weighted images and no appreciable enhancement on the
      postcontrast T1-weighted image; perimural hemorrhage exhibited normal thickness
      low SI wall on T2-weighted single shot images, with ill-defined material
      surrounding the bowel. SI features of this material, was similar to mural-based
      abnormality. CONCLUSION: In two patients with small bowel wall hemorrhage, the
      wall showed increased thickness with increased SI on noncontrast T1-weighted
      images and lack of enhancement on postgadolinium images. Perimural hematoma
      showed an intact normal thickness wall that was low SI on T2 with surrounding
      material that was high SI on noncontrast T1-weighted images and did not enhance.

PMID- 19388109
TI  - Diminished visibility of cerebral venous vasculature in multiple sclerosis by
      susceptibility-weighted imaging at 3.0 Tesla.
AB  - Multiple sclerosis (MS) is a disease of the central nervous system characterized
      by widespread demyelination, axonal loss and gliosis, and neurodegeneration;
      susceptibility-weighted imaging (SWI), through the use of phase information to
      enhance local susceptibility or T2* contrast, is a relatively new and simple MRI
      application that can directly image cerebral veins by exploiting venous blood
      oxygenation. Here, we use high-field SWI at 3.0 Tesla to image 15 patients with
      clinically definite relapsing-remitting MS and to assess cerebral venous oxygen
      level changes. We demonstrate significantly reduced visibility of periventricular
      white matter venous vasculature in patients as compared to control subjects,
      supporting the concept of a widespread hypometabolic MS disease process. SWI may
      afford a noninvasive and relatively simple method to assess venous oxygen
      saturation so as to closely monitor disease severity, progression, and response
      to therapy.

PMID- 19388110
TI  - MRI features of cellular angiomyofibroma with pathologic correlation.
AB  - Within the spectrum of extratesticular mesenchymal tumors in the scrotum and
      perineum lies cellular angiofibroma, also known as angiomyofibroblastoma-like
      tumor, a rare lesion originally described to almost exclusively occur in the
      vulva, perineum, and pelvis of women. We report a case of this tumor, with an
      adjacent scrotal lipoma, occurring in a 60-year-old male who presented to our
      department with a firm palpable scrotal mass. To our knowledge, the MRI findings
      of this entity have yet to be described in the radiological literature. We
      present the MRI features of cellular angiofibroma that are consistent with the
      pathological characteristics of this entity-a benign cellular and fibrous tumor
      with prominent vascularity.

PMID- 19388111
TI  - Peripheral moving-table contrast-enhanced magnetic resonance angiography (CE-MRA)
      using a prototype 18-channel peripheral vascular coil and scanning parameters
      optimized to the patient's individual hemodynamics.
AB  - PURPOSE: To demonstrate that with a priori determination of individual patient
      hemodynamics, peripheral contrast-enhanced magnetic resonance angiography (pCE
      MRA) can be customized to maximize signal-to noise ratio (SNR) and avoid venous
      enhancement. MATERIALS AND METHODS: Using a 1.5T MRI scanner and prototype 18
      channel peripheral vascular (PV) coil designed for highly accelerated parallel
      imaging, geometry (g)-factor maps were determined. SNR-maximized protocols
      considering the two-dimensional sensitivity encoding (2D SENSE) factor, TE, TR,
      bandwidth (BW), and flip angle (FA) were precalculated and stored. For each exam,
      a small aortic timing bolus was performed, followed by dynamic three-dimensional
      (3D)-MRA of the calf. Using this information, the aorta to pedal artery and calf
      arteriovenous transit times were measured. This enabled estimation of the maximum
      upper and middle station acquisition duration to allow lower station acquisition
      to begin prior to venous arrival. The appropriately succinct SNR-optimized
      protocol for each station was selected and moving-table pCE-MRA was performed
      using thigh venous compression and high-relaxivity contrast material. RESULTS:
      The protocol was successfully applied in 15 patients and all imaging demonstrated
      good SNR without diagnosis-hindering venous enhancement. CONCLUSION: By knowing
      each patient's venous enhancement kinetics, scan parameters can be optimized to
      utilize maximum possible acquisition time. Some time is added for the timing
      scans, but in return time-resolved calf CE-MRA, maximized SNR, and decreased risk
      of venous enhancement are gained.

PMID- 19388113
TI  - Repeatability of quantitative parameters derived from diffusion tensor imaging in
      patients with glioblastoma multiforme.
AB  - PURPOSE: To quantify the repeatability of apparent diffusion coefficient (ADC)
      and fractional anisotropy (FA) in patients with glioblastoma multiforme.
      MATERIALS AND METHODS: IRB approval and informed consent were obtained for this
      Health Insurance Portability and Accountability Act-compliant study. Sixteen
      patients with glioblastoma multiforme underwent MR imaging at two time points
      without interval intervention. ADC and FA maps were registered to the contrast
      enhanced and fluid-attenuated inversion recovery (FLAIR) image volumes. Volumes
      of tumor-related enhancement (TRE) and FLAIR signal abnormality (FSA) were
      defined using a semiautomated segmentation technique. RESULTS: Repeated
      observations of mean ADC and mean FA were highly consistent within both TRE (ADC:
      r = 0.947,P < 0.0001; FA: r = 0.947, P < 0.0001) and FSA (ADC: r = 0.979, P <
      0.0001; FA: r = 0.972, P < 0.0001). Within TRE, repeatability coefficients and
      95% confidence intervals (CIs) for change measured 0.104 x 10(-3) mm(2)S(-1) and
      7.4% (ADC) and 0.0196 and 13.9% (FA), respectively. Within FSA, repeatability
      coefficients and 95% CI for change measured 0.071 x 10(-3) mm(2)S(-1) and 5.2%
      (ADC) and 0.0159 and 8.7% (FA), respectively. To detect 10% changes in mean ADC,
      sample sizes of nine (TRE) and six (FSA) patients would be required. The same
      change in mean FA would require sample sizes of 21 (TRE) and 10 (FSA) patients,
      respectively. CONCLUSION: Changes after therapy greater than the repeatability
      coefficient or 95% CI for change are unlikely to be related to variability in the
      measurement of ADC and FA.

PMID- 19388112
TI  - In vivo quantification of femoral-popliteal compression during isometric thigh
      contraction: Assessment using MR angiography.
AB  - PURPOSE: To quantify femoral-popliteal vessel deformation during thigh
      contraction. MATERIALS AND METHODS: Eleven subjects underwent a magnetic
      resonance (MR) examination of the femoral-popliteal vasculature on a 1.5 T
      system. A custom 3D balanced steady-state free precession (SSFP) sequence was
      implemented to image a 15-20-cm segment of the vasculature during relaxation and
      voluntary isometric thigh contraction. The arterial and venous lumina were
      outlined using a semiautomated method. For the artery, this outline was fit to an
      ellipse whose aspect ratio was used to describe arterial deformation, while
      venous deformation was characterized by its cross-sectional area. RESULTS: Focal
      compression of the femoral-popliteal artery during contraction was observed 94
      143 mm superior to the condyle that corresponds to the distal adductor canal (AC)
      immediately superior to the adductor hiatus. This was illustrated by a
      significant reduction (P < or = 0.05) in aspect ratio from 0.88 +/- 0.06 during
      relaxation to 0.77 +/- 0.09 during contraction. A negligible change in arterial
      aspect ratio was observed inferior to the AC and in the proximal AC. Similarly,
      venous area was dramatically reduced in the distal AC region during contraction.
      CONCLUSION: Rapid 3D SSFP MR angiography of the femoral-popliteal vasculature
      during thigh contraction demonstrated focal compression of the artery in the
      distal AC region. This may help explain the high stent failure rate and the high
      likelihood of atherosclerotic disease in the AC. J. Magn. Reson.

PMID- 19388114
TI  - MRI methods for evaluating the effects of tyrosine kinase inhibitor
      administration used to enhance chemotherapy efficiency in a breast tumor
      xenograft model.
AB  - PURPOSE: To evaluate whether quantitative MRI parameters are sensitive to the
      effects of the tyrosine kinase inhibitor gefitinib and can discriminate between
      two different treatment protocols. MATERIALS AND METHODS: Untreated mice with
      BT474 breast tumor xenografts were characterized in a preliminary study.
      Subsequently, tumor volume, apparent diffusion coefficient (ADC),
      transendothelial permeability (K(ps)), and fractional plasma volume (fPV) were
      measured in three groups of mice receiving: 1) control vehicle for 10 days, or
      gefitinib as 2) a single daily dose for 10 days or 3) a 2-day pulsed dose.
      RESULTS: Gefitinib treatment resulted in significant tumor growth inhibition
      (pulsed: 439 +/- 93; daily: 404 +/- 53; control: 891 +/- 174 mm(3), P < 0.050)
      and lower cell density (pulsed: 0.15 +/- 0.01, daily: 0.17 +/- 0.01, control:
      0.24 +/- 0.01, P < 0.050) after 9 days. Tumor ADC increased in treated groups but
      decreased in controls (P > 0.050). Tumor K(ps) decreased with pulsed treatment
      but rebounded afterwards and increased with daily treatment (P > 0.050). Tumor
      fPV increased in both treated groups, decreasing afterwards with pulsed treatment
      (P > 0.050). CONCLUSION: Quantitative MRI can provide a sensitive measure of
      gefitinib-induced tumor changes, potentially distinguish between treatment
      regimens, and may be useful for determining optimal treatment scheduling for
      enhancing chemotherapy delivery.

PMID- 19388115
TI  - Microperfusion-induced elevation of ADC is suppressed after contrast in breast
      carcinoma.
AB  - PURPOSE: To investigate the effect of gadolinium (Gd)-DTPA on the apparent
      diffusion coefficient (ADC) of breast carcinoma and to analyze the relationship
      between pre/postcontrast ADC and the degree of contrast enhancement. MATERIALS
      AND METHODS: Nineteen histopathologically confirmed breast carcinomas (mean size
      = 22 mm) were analyzed. Their ADCs before and after contrast administration were
      measured. The contrast-to-noise ratios (CNRs) of the tumors were measured on fat
      suppressed 3D T1-weighted images in precontrast, early, and late postcontrast
      phases. These results were correlated with the measured ADC values. RESULTS: A
      significant decrease in the measured ADC was noted after contrast administration
      (-23%, P = 0.01). Lesions with relatively high ADC before contrast (>1.3 x 10(-3)
      mm(2)/sec; n = 12) demonstrated a larger degree of ADC reduction (mean 34%) than
      lesions with low ADC (< or =1.3 x 10(-3) mm(2)/sec; n = 7) (mean 4.5%). When an
      early postcontrast image was used as a surrogate marker of malignant potential,
      we found a significant inverse correlation with postcontrast ADC (gamma = -0.57,
      P = 0.02). CONCLUSION: Postcontrast ADC exhibited lower values than precontrast
      ADC, which is thought to reflect suppression of the microperfusion-induced effect
      on diffusion-weighted imaging. Postcontrast ADC may be a better indicator than
      precontrast ADC to reflect malignant potential of tumors.

PMID- 19388116
TI  - Three common polymorphisms in the CYBA gene form a haplotype associated with
      decreased ROS generation.
AB  - NOX enzymes are reactive oxygen species (ROS)-generating NADPH oxidases. Several
      members of the NOX family depend on the p22(phox) subunit, encoded by the CYBA
      gene. CYBA is highly polymorphic, and has been widely studied as a potential risk
      factor for various diseases, with conflicting results. In the present study, we
      used Epstein-Barr (EBV)-transformed B-lymphocytes from 50 healthy unrelated
      individuals to analyze their CYBA mRNA sequence and NOX2-dependent ROS
      generation. Seven single-nucleotide polymorphisms (SNPs) were identified (five
      previously described, two novel). The combination of these SNPs yielded 11
      distinct haplotypes, which could be grouped into seven haplogroups (A-G).
      Haplogroup C (c.214T>C, c.521T>C, and c.(*)24G>A) showed a significantly lower
      ROS generation, as compared to the most frequent haplogroup, A. CYBA variants
      from the seven haplogroups were transduced into p22(phox)-deficient B
      lymphocytes. The haplogroup C variant showed significantly lower ROS production.
      c.214T>C and c.521T>C lead to nonsynonymous codon changes, while c.(*)24G>A lies
      within the 3'UTR. Using a luciferase/3'UTR construct, we showed that the (*)24A
      allele led to decreased reporter gene activity. These results help to unravel the
      complex nature of how genetic variations in CYBA influence NOX2 activity, and
      indicate that haplotypes, rather than individual SNPs, define the effect on ROS
      generation.

PMID- 19388117
TI  - Assessment of vascular remodeling under antiangiogenic therapy using DCE-MRI and
      vessel size imaging.
AB  - PURPOSE: To assess vascular remodeling in tumors during two different
      antiangiogenic therapies with dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) and vessel size imaging and to evaluate the vessel size index
      (VSI) as a novel biomarker of therapy response. MATERIALS AND METHODS: In two
      independent experiments, nude mice bearing human skin squamous cell carcinoma
      xenografts were treated with a vascular endothelial growth factor (VEGF)
      inhibitor (bevacizumab) or a multitargeted tyrosine kinase inhibitor (SU11248).
      Changes in tumor vascularity were assessed by DCE-MRI and vessel size imaging.
      DCE-MRI data were analyzed applying a two-compartment model (Brix), calculating
      the parameters Amplitude and k(ep). RESULTS: For both experiments Amplitude
      decreased significantly in treated tumors while k(ep) did not change
      significantly. VSI showed controversial results. VSI was significantly increased
      in SU11248-treated A431 tumors, whereas no changes were found in bevacizumab
      treated HaCaT-ras-A-5RT3 tumors. Immunohistology confirmed these results and
      suggest differences in the maturation of tumor vascularization as a possible
      explanation. CONCLUSION: DCE-MRI and vessel size imaging provide reliable and
      supplementing biomarkers of antiangiogenic therapy response. The results of both
      methods are in excellent agreement with histology. Nevertheless, our results also
      indicate that vascular remodeling is complex and that a uniform response cannot
      be expected for different tumors and therapies.

PMID- 19388118
TI  - A fast, effective filtering method for improving clinical pulsed arterial spin
      labeling MRI.
AB  - PURPOSE: To evaluate the effectiveness of a fully automated postprocessing filter
      algorithm in pulsed arterial spin labeling (PASL) MRI perfusion images in a large
      clinical population. MATERIALS AND METHODS: A mean and standard deviation-based
      filter was implemented to remove outliers in the set of perfusion-weighted images
      (control - label) before being averaged and scaled to quantitative cerebral blood
      flow (CBF) maps. Filtered and unfiltered CBF maps from 200 randomly selected
      clinical cases were assessed by four blinded raters to evaluate the effectiveness
      of the filter. RESULTS: The filter salvaged many studies deemed uninterpretable
      as a result of motion artifacts, transient gradient, and/or radiofrequency
      instabilities, and unexpected disruption of data acquisition by the technologist
      to communicate with the patient. The filtered CBF maps contained significantly (P
      < 0.05) fewer artifacts and were more interpretable than unfiltered CBF maps as
      determined by one-tail paired t-test. CONCLUSION: Variations in MR perfusion
      signal related to patient motion, system instability, or disruption of the steady
      state can introduce artifacts in the CBF maps that can be significantly reduced
      by postprocessing filtering. Diagnostic quality of the clinical perfusion images
      can be improved by performing selective averaging without a significant loss in
      perfusion signal-to-noise ratio.

PMID- 19388119
TI  - Non-contrast-enhanced MR portography with time-spatial labeling inversion pulses:
      comparison of imaging with three-dimensional half-fourier fast spin-echo and true
      steady-state free-precession sequences.
AB  - PURPOSE: To compare and evaluate images acquired with two different MR
      angiography (MRA) sequences, three-dimensional (3D) half-Fourier fast spin-echo
      (FSE) and 3D true steady-state free-precession (SSFP) combined with two time
      spatial labeling inversion pulses (T-SLIPs), for selective and non-contrast
      enhanced (non-CE) visualization of the portal vein. MATERIALS AND METHODS: Twenty
      healthy volunteers were examined using half-Fourier FSE and true SSFP sequences
      on a 1.5T MRI system with two T-SLIPs, one placed on the liver and thorax, and
      the other on the lower abdomen. For quantitative analysis, vessel-to-liver
      contrast (Cv-l) ratios of the main portal vein (MPV), right portal vein (RPV),
      and left portal vein (LPV) were measured. The quality of visualization was also
      evaluated. RESULTS: In both pulse sequences, selective visualization of the
      portal vein was successfully conducted in all 20 volunteers. Quantitative
      evaluation showed significantly better Cv-l at the RPVs and LPVs in half-Fourier
      FSE (P < 0.0001). At the MPV, Cv-l was better in true SSFP, but was not
      statistically different. Visualization scores were significantly better only at
      branches of segments four and eight for half-Fourier FSE (P = 0.001 and 0.03,
      respectively). CONCLUSION: Both 3D half-Fourier FSE and true SSFP scans with T
      SLIPs enabled selective non-CE visualization of the portal vein. Half-Fourier FSE
      was considered appropriate for intrahepatic portal vein visualization, and true
      SSFP may be preferable when visualization of the MPV is required.

PMID- 19388120
TI  - Improved vessel delineation in keyhole time-resolved contrast-enhanced MR
      angiography using a gadolinium doped flush.
AB  - PURPOSE: To prospectively assess the influence of a gadolinium doped saline flush
      compared with a pure saline flush on the image quality of the supra-aortic
      vessels using time-resolved contrast-enhanced MR angiography (4D CE-MRA) in a
      randomized double blind clinical trial. MATERIALS AND METHODS: Twenty-two
      patients scheduled for contrast-enhanced craniocerebral MRI underwent a
      supplemental 4D CE-MRA covering the carotids to the superior sinus consisting of
      30 dynamics of a T1-weighted 3D gradient-echo sequence (FFE) in sagittal
      direction. The temporal resolution of 1.1 s per dataset was achieved using the
      keyhole technique with the reference scan acquired at the end. Immediately after
      the intravenous (IV) injection of 0.1 mmol Gd/kg body weight of gadoterate, our
      patients received a 50-mL flush consisting either of a 0.9% saline solution (n =
      11) or doped with 50 mM gadolinium (n = 11; total Gd: 0.11 mmol/kg) at a flow
      rate of 2 mL/s. Vessel delineation, image quality, signal-to-noise- (SNR) and
      contrast-to-noise (CNR) ratios over time were compared. RESULTS: Both vessel
      delineation (internal carotid artery [ICA]: slope(saline) = 308.5; slope(Gd) =
      528.9; P = 0.006; superior sagittal sinus [SSS]: slope(saline) = 505.3; slope(Gd)
      = 674.9; P = 0.007) and CNR (ICA: CNR(saline) = 57.3; CNR(Gd) = 80.55; P =
      0.0417; SSS: CNR(saline) = 74.15; CNR(Gd) = 117.4; P = 0.0331) of the ICA and SSS
      were significantly increased using the gadolinium doped flush. CONCLUSION: A low
      concentrated gadolinium flush in comparison to a pure saline flush improves
      significantly vessel contrast and their delineation in time-resolved CE-MRA using
      the keyhole technique.

PMID- 19388121
TI  - Fast dixon-based multisequence and multiplanar MRI for whole-body detection of
      cancer metastases.
AB  - PURPOSE: To develop and demonstrate the feasibility of multisequence and
      multiplanar MRI for whole-body cancer detection. MATERIALS AND METHODS: Two fast
      Dixon-based sequences and a diffusion-weighted sequence were used on a
      commercially available 1.5 T scanner for whole-body cancer detection. The study
      enrolled 19 breast cancer patients with known metastases and in multistations
      acquired whole-body axial diffusion-weighted, coronal T2-weighted, axial/sagittal
      pre- and postcontrast T1-weighted, as well as triphasic abdomen images. Three
      radiologists subjectively scored Dixon images of each series for overall image
      quality and fat suppression uniformity on a 4-point scale (1 = poor, 2 = fair, 3
      = good, and 4 = excellent). RESULTS: Eighteen of the 19 patients completed the
      whole-body MRI successfully. The mean acquisition time and overall patient table
      time were 46 +/- 3 and 69 +/- 5 minutes, respectively. The average radiologists'
      scores for overall image quality and fat suppression uniformity were both 3.4 +/-
      0.5. The image quality was consistent between patients and all completed whole
      body examinations were diagnostically adequate. CONCLUSION: Whole-body MRI
      offering essentially all the most optimal tumor-imaging sequences in a typical 1
      hour time slot can potentially become an appealing "one-stop-shop" for whole-body
      cancer imaging.

PMID- 19388123
TI  - Changes in hepatic venous morphology with cirrhosis on MRI.
AB  - PURPOSE: To identify changes in vascular morphology on magnetic resonance imaging
      (MRI) in patients with cirrhosis and to compare these findings to liver donors.
      MATERIALS AND METHODS: Patients undergoing liver transplantation with biopsy
      proven cirrhosis (n = 74) and liver donor candidates (n = 85) underwent dynamic
      gadolinium-enhanced 3D MR at 1.5T. Vessel diameters were measured independently
      by three radiologists and features of cirrhosis were identified and correlated
      with cirrhosis. RESULTS: Hepatic veins were smaller in patients with cirrhosis
      (4.9, 4.5, and 5.0 mm for right, middle, and left vs. 9.9, 7.6, and 8.9 mm in
      donors, P << 0.001) and were negatively correlated with cirrhosis (P < 0.001).
      Right hepatic vein (RHV) <5 mm diagnosed cirrhosis with 59% sensitivity and 99%
      specificity; the sensitivity and specificity were 88% and 85% for RHV <7 mm. Main
      portal vein was minimally larger in cirrhosis, 14 versus 12 mm (P < 0.001) in
      donors. Right portal veins were smaller in cirrhotic patients, 6.5 and 6.2 mm
      compared to 8.4 and 7.6 mm (P << 0.001), respectively, in donors. CONCLUSION:
      Vascular features of cirrhosis include small hepatic veins, minimally enlarged
      main portal vein, and small intrahepatic portal veins; these features may
      facilitate identification of cirrhosis.

PMID- 19388122
TI  - Improved cerebellar tissue classification on magnetic resonance images of brain.
AB  - PURPOSE: To develop and implement a method for improved cerebellar tissue
      classification on the MRI of brain by automatically isolating the cerebellum
      prior to segmentation. MATERIALS AND METHODS: Dual fast spin echo (FSE) and fluid
      attenuation inversion recovery (FLAIR) images were acquired on 18 normal
      volunteers on a 3 T Philips scanner. The cerebellum was isolated from the rest of
      the brain using a symmetric inverse consistent nonlinear registration of
      individual brain with the parcellated template. The cerebellum was then separated
      by masking the anatomical image with individual FLAIR images. Tissues in both the
      cerebellum and rest of the brain were separately classified using hidden Markov
      random field (HMRF), a parametric method, and then combined to obtain tissue
      classification of the whole brain. The proposed method for tissue classification
      on real MR brain images was evaluated subjectively by two experts. The
      segmentation results on Brainweb images with varying noise and intensity
      nonuniformity levels were quantitatively compared with the ground truth by
      computing the Dice similarity indices. RESULTS: The proposed method significantly
      improved the cerebellar tissue classification on all normal volunteers included
      in this study without compromising the classification in remaining part of the
      brain. The average similarity indices for gray matter (GM) and white matter (WM)
      in the cerebellum are 89.81 (+/-2.34) and 93.04 (+/-2.41), demonstrating
      excellent performance of the proposed methodology. CONCLUSION: The proposed
      method significantly improved tissue classification in the cerebellum. The GM was
      overestimated when segmentation was performed on the whole brain as a single
      object.

PMID- 19388124
TI  - Accuracy of MRI for predicting the circumferential resection margin, mesorectal
      fascia invasion, and tumor response to neoadjuvant chemoradiotherapy for locally
      advanced rectal cancer.
AB  - PURPOSE: To evaluate the diagnostic accuracy of MRI for predicting the
      circumferential resection margin (CRM), mesorectal fascia (MRF) invasion, and the
      tumor response to neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal
      cancer. MATERIALS AND METHODS: Sixty-five consecutive patients with locally
      advanced rectal cancer (> or =T3 or lymph node-positive) who underwent
      neoadjuvant CRT and subsequent surgery were enrolled in this retrospective study.
      Two blinded radiologists independently reviewed both the pre- and post-CRT rectal
      MR images and measured the post-CRT CRM; they recorded their confidence level
      with respect to the MRF invasion and tumor response using a 5-point scale. The
      diagnostic accuracy of each reviewer was calculated using receiver operating
      characteristic curve (ROC) analysis. RESULTS: The measured CRM was not
      significantly different from the reference standard (mean difference, -1.4 mm;
      95% limits of agreement, -8.3-5.4 mm; interclass correlation coefficient, 0.82).
      The diagnostic accuracy (A(z)) for determining MRF invasion was 0.890 for
      reviewer 1 (95% confidence interval [CI], 0.788-0.954) and 0.829 for reviewer 2
      (95% CI, 0.715-0.911). The A(z) for predicting complete or near-complete
      regression was 0.791 for reviewer 1 (95% CI, 0.672-0.882) and 0.735 for reviewer
      2 (95% CI, 0.611-0.837). CONCLUSION: MRI provides accurate information regarding
      the CRM of locally advanced rectal cancer after neoadjuvant CRT; it also shows
      relatively high accuracy for predicting MRF invasion and moderate accuracy for
      assessing tumor response.

PMID- 19388125
TI  - Palmar bowing of the flexor retinaculum on wrist MRI correlates with subjective
      reports of pain in carpal tunnel syndrome.
AB  - PURPOSE: To investigate the utility of palmar bowing of the flexor retinaculum
      (PBFR) on magnetic resonance imaging (MRI) as an adjunct to presurgical
      evaluation of carpal tunnel syndrome (CTS). MATERIALS AND METHODS: The CTS group
      comprised 48 women with CTS diagnosed from clinical history, physical
      examination, and electrophysiological findings. Another 21 healthy women with no
      symptoms of CTS served as controls. The CTS group was divided into four subgroups
      based on symptom duration. CTS patients were preoperatively assessed for symptom
      severity using a Likert scale. In both groups, palmar bowing of the flexor
      retinaculum (PBFR) was measured on MRI. Furthermore, relationships with disease
      duration, subjective symptom severity, and electrophysiological findings were
      assessed in the CTS group. RESULTS: Although PBFR increased significantly in all
      CTS groups when compared to the control group, PBFR in patients who complained of
      severe pain tended to exceed that in patients with mild to moderate pain.
      Statistical analysis showed a positive correlation between PBFR and pain
      severity. In contrast, PBFR did not reflect median nerve function. CONCLUSION:
      PBFR as seen on MRI seems to correlate significantly with patients' subjective
      reports of pain severity.

PMID- 19388126
TI  - Feasibility and reproducibility of biventricular volumetric assessment of cardiac
      function during exercise using real-time radial k-t SENSE magnetic resonance
      imaging.
AB  - PURPOSE: To assess the feasibility and reproducibility of real-time radial k-t
      sensitivity encoding (SENSE) magnetic resonance imaging (MRI) for biventricular
      volumetric assessment during exercise. MATERIALS AND METHODS: In all, 12 healthy
      young adults underwent MRI at rest and during supine exercise at three different
      workload intensities. Biventricular volumes and function were assessed with 1) a
      radial k-t SENSE real-time sequence and 2) a scanner vendor supplied (standard)
      real-time sequence. Global image quality, motion fidelity, and agreement in right
      ventricular (RV) and left ventricular (LV) stroke volume (SV) as a surrogate
      measure for accuracy were assessed. Exercise MR was repeated within 1 month for
      assessment of reproducibility. RESULTS: Imaging scores were superior for radial
      real-time k-t SENSE images (P < 0.001). Agreement in RV and LV SV during exercise
      was better with radial k-t real-time (SD of difference +/-3.43 vs. +/-8.97 mL; P
      < 0.001). Agreement in cardiac output (CO) in the same subject at two different
      imaging sessions was better for radial k-t SENSE. This was significant for the CO
      calculated for the RV (SD of difference +/-0.6 vs. +/-0.95 L/min; P = 0.01) and
      LV (+/-0.45 vs. +/-0.92 L/min; P < 0.001). CONCLUSION: Radial k-t SENSE real-time
      imaging represents a feasible and reproducible imaging technique for
      biventricular assessment during exercise.

PMID- 19388127
TI  - Molecular karyotyping of patients with unexplained mental retardation by SNP
      arrays: a multicenter study.
AB  - Genomic microarrays have been implemented in the diagnosis of patients with
      unexplained mental retardation. This method, although revolutionizing
      cytogenetics, is still limited to the detection of rare de novo copy number
      variants (CNVs). Genome-wide single nucleotide polymorphism (SNP) microarrays
      provide high-resolution genotype as well as CNV information in a single
      experiment. We hypothesize that the widespread use of these microarray platforms
      can be exploited to greatly improve our understanding of the genetic causes of
      mental retardation and many other common disorders, while already providing a
      robust platform for routine diagnostics. Here we report a detailed validation of
      Affymetrix 500k SNP microarrays for the detection of CNVs associated to mental
      retardation. After this validation we applied the same platform in a multicenter
      study to test a total of 120 patients with unexplained mental retardation and
      their parents. Rare de novo CNVs were identified in 15% of cases, showing the
      importance of this approach in daily clinical practice. In addition, much more
      genomic variation was observed in these patients as well as their parents. We
      provide all of these data for the scientific community to jointly enhance our
      understanding of these genomic variants and their potential role in this common
      disorder.

PMID- 19388128
TI  - Regional atrophy of transcallosal prefrontal connections in cognitively normal
      APOE epsilon4 carriers.
AB  - PURPOSE: To investigate the possible effect of the APOE epsilon4 allele on age
      related regional volume loss within the corpus callosum (CC) in healthy epsilon4
      allele carriers compared with noncarriers. MATERIALS AND METHODS: A total of 211
      subjects, ages 27 to 83 years, 51 epsilon4 carriers and 160 noncarriers underwent
      T1-weighted MRI scan. All subjects had normal MRI scan and performed within
      normal range on a neuropsychological battery of tests. CC was segmented into
      seven functionally relevant regions using a previously published probabilistic
      map of the CC connectivity. We measured the volumes of the CC and its subregions.
      We used a regression model (with volumes as dependent and age as independent
      variables) and compared the slopes between carriers and noncarriers using an
      analysis of covariance model. We also carried out voxel-based-morphometry
      analysis to investigate the possible effect of the APOE epsilon4 gene on the gray
      matter. RESULTS: We found that the volume of the CC and all subregions decreased
      with increasing age in both groups. The slope was steeper in the APOE epsilon4
      carriers compared withthe noncarriers particularly in the prefrontal region (P =
      0.02). No gray matter differences were observed between the two groups.
      CONCLUSION: APOE epsilon4 polymorphism is associated with accelerated age-related
      volume loss in the prefrontal callosal tracts without gray matter loss. This
      result suggests the role of APOE epsilon4 in the brain aging by primarily
      affecting white matter structures particularly in the frontal lobe.

PMID- 19388129
TI  - MRI-based large deformation high dimensional mapping of the hippocampus in rats:
      development and validation of the technique.
AB  - PURPOSE: To report the detection of structural and functional biological changes
      in living animals using small animal in vivo MRI that complements traditional ex
      vivo histological techniques. We report the development and validation of the
      application of large deformation high dimensional mapping (HDM-LD) segmentation
      for the hippocampus in the rat. MATERIALS AND METHODS: High resolution volumetric
      T2 weighted MRI images were acquired at 4.7 Tesla from six male in-breed
      nonepileptic Wistar rats. Two HDM-LD segmentations of the hippocampus (automated
      1 and automated 2) were compared with the manual segmentations of two
      investigators who independently segmented the hippocampi (manual 1 and manual 2).
      RESULTS: The mean overlap for the hippocampi between automated 1 and automated 2
      for the right hippocampi was 94.4% (SD 1.0) and for the left hippocampi was 94.3%
      (SD 2.5), while the mean overlap between automated 1 and manual 1 for the right
      hippocampi was 91.4% (SD 1.3) and for the left hippocampi was 91.9% (SD 1.4).
      Mean values for absolute differences for comparisons of all the segmentations
      were the following: automated 1 versus automated 2, 3.2% (SD 1.0); manual 1
      versus manual 2 6.82% (SD 5.22); automated 1 versus manual 1 13.0% (SD 1.8).
      CONCLUSION: HDM-LD can be applied to obtain accurate and reproducible three
      dimensional segmentations of the hippocampus from rat MR images. HDM-LD will be a
      useful tool for investigations of hippocampal structural changes in vivo in rat
      models of human disease.

PMID- 19388130
TI  - Visualization of multidirectional regional left ventricular dynamics by high
      temporal-resolution tissue phase mapping.
AB  - PURPOSE: To apply high-temporal-resolution tissue phase mapping (TPM) to derive a
      detailed representation of normal regional myocardial motion in a large cohort of
      58 normal subjects (three age groups) and one patient with dilated
      cardiomyopathy. MATERIALS AND METHODS: Analysis included transformation of the
      acquired myocardial velocities into radial, circumferential, and long-axis motion
      components representing left ventricular (LV) function with a spatiotemporal
      resolution of 1.3 x 2.6 x 8 mm(3) and 13.8 msec, respectively. To compare
      multidirectional regional myocardial velocities between groups of subjects, a
      multisegment and multislice visualization model was employed. Regional myocardial
      motion was mapped onto the visualization model to display the current status of
      myocardial motion from base to apex as in-plane velocity vector fields in
      conjunction with color-coded long-axis plane motion. Moreover, correlation
      analysis was used to investigate regional differences in myocardial dynamics.
      RESULTS: Age-related changes in LV myocardial velocities resulted in significant
      differences of peak and time-to-peak velocities in the radial and long-axis
      directions. Correlation analysis revealed clearly visible regional differences in
      the temporal evolution of long-axis and circumferential velocities, particularly
      between the youngest and oldest age groups. Comparison of pathological LV motion
      with age-matched volunteers indicated marked regional alterations in myocardial
      velocities and dynamics. CONCLUSION: High-temporal-resolution TPM in combination
      with a schematic visualization model and correlation analysis permits the
      identification of local changes in myocardial velocities associated with
      different age groups and a common LV pathology.

PMID- 19388131
TI  - Strain-encoded cardiac MR during high-dose dobutamine stress testing: comparison
      to cine imaging and to myocardial tagging.
AB  - PURPOSE: To investigate regional strain response during high-dose dobutamine
      stress cardiac magnetic resonance imaging (DS-CMR) using myocardial tagging and
      Strain-Encoded MR (SENC). MATERIALS AND METHODS: Stress induced ischemia was
      assessed by wall motion analysis, by tagged CMR and by SENC in 65 patients with
      suspected or known CAD who underwent DS-CMR in a clinical 1.5 Tesla scanner.
      Coronary angiography deemed as the standard reference for the presence or absence
      of CAD (> or =50% diameter stenosis) in all patients. RESULTS: SENC and
      conventional tagging detected abnormal strain response in six and five additional
      patients, respectively, who were missed by cine images and proved to have CAD by
      angiography (P < 0.05 for SENC versus cine, P = 0.06 for tagging versus cine and
      p = NS for SENC versus tagging). On a per-vessel level, wall motion analysis on
      cine images showed high specificity (95%) but moderate sensitivity (70%) for the
      detection of CAD. Tagging and SENC yielded significantly higher sensitivity of
      81% and 89%, respectively (P < 0.05 for tagging and P < 0.01 for SENC versus wall
      motion analysis, and p = NS for SENC versus tagging), while specificity was
      equally high (96% and 94%, respectively, P = NS for all). CONCLUSION: Both the
      direct color-coded visualization of strain on CMR images and the generation of
      additional visual markers within the myocardium with tagged CMR represent useful
      adjuncts for DS-CMR, which may provide incremental value for the detection of CAD
      in humans. J. Magn. Reson.

PMID- 19388134
TI  - Extraction chemistry of fermentation product carboxylic acids.

PMID- 19388135
TI  - Host cell proteins in biologics development: Identification, quantitation and
      risk assessment.
AB  - Host cell proteins (HCPs) are those produced or encoded by the organisms and
      unrelated to the intended recombinant product. Some are necessary for growth,
      survival, and normal cellular processing whereas others may be non-essential,
      simply carried along as baggage. Like the recombinant product, HCPs may also be
      modified by the host with a number of post-translational modifications.
      Regardless of the utility, or lack thereof, HCPs are undesirable in the final
      drug substance. Though commonly present in small quantities (parts per million
      expressed as nanograms per milligrams of the intended recombinant protein) much
      effort and cost is expended by industry to remove them. The purpose of this
      review is to summarize what is of relevance in regards to the biology, the impact
      of genomics and proteomics on HCP evaluation, the regulatory expectations,
      analytical approaches, and various methodologies to remove HCPs with
      bioprocessing. Historical data, bioinformatics approaches and industrial case
      study examples are provided. Finally, a proposal for a risk assessment tool is
      provided which brings these facets together and proposes a means for
      manufacturers to classify and organize a control strategy leading to meaningful
      product specifications.

PMID- 19388138
TI  - P-type ATPases as drug targets: tools for medicine and science.
AB  - P-type ATPases catalyze the selective active transport of ions like H+, Na+, K+,
      Ca2+, Zn2+, and Cu2+ across diverse biological membrane systems. Many members of
      the P-type ATPase protein family, such as the Na+,K+-, H+,K+-, Ca2+-, and H+
      ATPases, are involved in the development of pathophysiological conditions or
      provide critical function to pathogens. Therefore, they seem to be promising
      targets for future drugs and novel antifungal agents and herbicides. Here, we
      review the current knowledge about P-type ATPase inhibitors and their present use
      as tools in science, medicine, and biotechnology. Recent structural information
      on a variety of P-type ATPase family members signifies that all P-type ATPases
      can be expected to share a similar basic structure and a similar basic machinery
      of ion transport. The ion transport pathway crossing the membrane lipid bilayer
      is constructed of two access channels leading from either side of the membrane to
      the ion binding sites at a central cavity. The selective opening and closure of
      the access channels allows vectorial access/release of ions from the binding
      sites. Recent structural information along with new homology modeling of diverse
      P-type ATPases in complex with known ligands demonstrate that the most proficient
      way for the development of efficient and selective drugs is to target their ion
      transport pathway.

PMID- 19388139
TI  - The chemistry of the CuB site in cytochrome c oxidase and the importance of its
      unique His-Tyr bond.
AB  - The CuB metal center is at the core of the active site of the heme-copper
      oxidases, comprising a copper atom ligating three histidine residues one of which
      is covalently bonded to a tyrosine residue. Using quantum chemical methodology,
      we have studied the CuB site in several redox and ligand states proposed to be
      intermediates of the catalytic cycle. The importance of the His-Tyr crosslink was
      investigated by comparing energetics, charge, and spin distributions between
      systems with and without the crosslink. The His-Tyr bond was shown to decrease
      the proton affinity and increase the electron affinity of both Tyr-244 and the
      copper. A previously unnoticed internal electronic equilibrium between the copper
      atom and the tyrosine was observed, which seems to be coupled to the unique
      structure of the system. In certain states the copper and Tyr-244 compete for the
      unpaired electron, the localization of which is determined by the oxygenous
      ligand of the copper. This electronic equilibrium was found to be sensitive to
      the presence of a positive charge 10 A away from the center, simulating the
      effect of Lys-319 in the K-pathway of proton transfer. The combined results
      provide an explanation for why the heme-copper oxidases need two pathways of
      proton uptake, and why the K-pathway is active only in the second half of the
      reaction cycle.

PMID- 19388140
TI  - The duty to inspect the skin and counsel those at risk to develop melanoma.

PMID- 19388141
TI  - Characterization of a novel splicing variant in the RAPTOR gene.
AB  - The mammalian target of rapamycin (mTOR) plays an essential role in the
      regulation of cell growth, proliferation and apoptosis. Raptor, the regulatory
      associated protein of mTOR, is an important member in this signaling pathway. In
      the present report,we identified and characterized a novel splicing variant of
      this gene, RAPTOR v2, in which exons 14-17, 474 bp in total, are omitted from the
      mRNA. This deletion does not change the open reading frame, but causes a nearly
      complete absence of HEAT repeats, which were shown to be involved in the binding
      of mTOR substrates. Real time PCR performed on 48 different human tissues
      demonstrated the ubiquitous presence of this splice variant. Quantification of
      mRNA levels in lymphoblastoid cell lines (LCL) from 56 unrelated HapMap
      individuals revealed that the expression of this splicing form is quite variable.
      One synonymous SNP, rs2289759 in exon 14, was predicted by ESEfinder to cause a
      significant gain/loss of SRp55 and/or SF2/ASF binding sites, and thus potentially
      influence splicing. This prediction was confirmed by linear regression analysis
      between the ratio of RAPTOR v2 to total RAPTOR mRNA levels and the SNP genotype
      in the above 56 individuals (r=0.281 and P=0.036). Moreover, the functional
      evaluation indicated that this splicing isoform is expected to retain the ability
      to bind mTOR, but is unlikely to bind mTOR substrates, hence affecting signal
      transduction and further cell proliferation.

PMID- 19388142
TI  - Mycobacterial ecology as a modulator of tuberculosis vaccine success.
AB  - Natural infection with Mycobacterium tuberculosis, as well as cross-immune
      reactions with the constituent of standard vaccines, attenuated M. bovis, and
      other species of mycobacteria confer partial immunity to subsequent M.
      tuberculosis infection. It has been shown in the past that the immune response to
      mycobacteria found naturally in the environment reduces the benefit of
      vaccination as assessed by means of vaccine efficacy. In this paper we show that
      efficacy is a poor measure of the potential success of new anti-tuberculous
      vaccines due to its inability to account for the relative weight of reinfection
      in disease dynamics. We advocate instead the use of vaccine effectiveness when
      evaluating the impact of new control methods against infections that confer
      partial immunity. Through the study of a simple model that incorporates cross
      reactive responses to environmental mycobacteria (EM) and reinfection, we show
      how the particulars of the relation between EM abundance and vaccine
      effectiveness depend on the degree of protection conferred respectively by
      natural infection, vaccination and EM. The relative importance of reinfection as
      a transmission mechanism comes up as the most important source of variability in
      vaccine effectiveness. Our results suggest that control efforts should be placed
      in reducing the importance of reinfection through diminishing transmission rates.
      Vaccines that overcome preexisting immunity to other mycobacteria will still have
      varying degrees of success depending on the underlying rate of TB transmission.

PMID- 19388143
TI  - Duality, ancestral and diffusion processes in models with selection.
AB  - The ancestral selection graph in population genetics was introduced by Krone and
      Neuhauser [Krone, S.M., Neuhauser, C., 1997. Ancestral process with selection.
      Theor. Popul. Biol. 51, 210-237] as an analogue of the coalescent genealogy of a
      sample of genes from a neutrally evolving population. The number of particles in
      this graph, followed backwards in time, is a birth and death process with
      quadratic death and linear birth rates. In this paper an explicit form of the
      probability distribution of the number of particles is obtained by using the
      density of the allele frequency in the corresponding diffusion model obtained by
      Kimura [Kimura, M., 1955. Stochastic process and distribution of gene frequencies
      under natural selection. Cold Spring Harbor Symposia on Quantitative Biology 20,
      33-53]. It is shown that the process of fixation of the allele in the diffusion
      model corresponds to convergence of the ancestral process to its stationary
      measure. The time to fixation of the allele conditional on fixation is studied in
      terms of the ancestral process.

PMID- 19388145
TI  - Distinctive EEG patterns in patients with Wolf-Hirschhorn  syndrome.

PMID- 19388146
TI  - Expression of CD147 on phorbol-12-myristate-13-acetate (PMA)-treated U937 cells
      differentiating into foam cells.
AB  - Monocytes, macrophages, and foam cells expressing CD147 can stimulate the
      production of several matrix metalloproteinases (MMPs) associated with the
      development of atherosclerosis. We defined theCD147 expression profile and
      examined the correlation between foam cell development and MMP-2, -9 expressions.
      Foam cells were derived from U937-stimulated macrophages using various
      concentrations of oxidized low-density lipoprotein (ox-LDL). PMA-stimulated U937
      cells had a 4- to 5-fold increase in CD147 mRNA compared to undifferentiated
      monocytes and membrane-associated (mCD147) on foam cells decreased in response to
      ox-LDL in a dose-dependent manner compared to untreated macrophages.In contrast,
      ox-LDL treatment increased the levels of soluble CD147 (sCD147) and MMP-2, -9 in
      a dose-dependent manner. Our data suggested that monocyte differentiation up
      regulated CD147 expression and lipid enrichment of foam cells had no effect on
      CD147 mRNA expression. Lipid loading in macrophages reduced mCD147 expression
      while increasing the levels of MMP-2, -9 and sCD147 in supernatants.

PMID- 19388144
TI  - Identifying catalytic residues in CPAF, a Chlamydia-secreted protease.
AB  - A secreted chlamydial protease designated CPAF (Chlamydial Protease/proteasome
      like Activity Factor) degrades host proteins, enabling Chlamydia to evade host
      defenses and replicate. The mechanistic details of CPAF action, however, remain
      obscure. We used a computational approach to search the protein databank for
      structures that are compatible with the CPAF amino acid sequence. The results
      reveal that CPAF possesses a fold similar to that of the catalytic domains of the
      tricorn protease from Thermoplasma acidophilum,and that CPAF residues H105, S499,
      and E558 are structurally analogous to the tricorn protease catalytic triad
      residues H746, S965, and D1023. Substitution of these putative CPAF catalytic
      residues blocked CPAF from degrading substrates in vitro, while the wild type and
      a noncatalytic control mutant of CPAF remained cleavage-competent. Substrate
      cleavage is also correlated with processing of CPAF into N-terminal (CPAFn) and C
      terminal (CPAFc) fragments, suggesting that these putative catalytic residues may
      also be required for CPAF maturation.

PMID- 19388148
TI  - Trends in prevalence and characteristics of cerebral palsy among  Icelandic
      children born 1990 to 2003.
AB  - AIM: To describe trends in cerebral palsy (CP) prevalence, severity, and
      associated impairments among 139 Icelandic children (65 males, 74 females) born
      from 1990 to 1996 (period one) and 1997 to 2003 (period two). METHOD: A
      population-based study using systematically collected data on motor functioning
      and associated impairments of children with CP. Mean age at assessment was 5
      years 5 months (SD 7.68 mo) in period one and 5 years 5 months (SD 10.44 mo) in
      period two. Infants with postneonatal CP were excluded. RESULTS: Prevalence of CP
      per 1000 live births was 2.2 in period one and 2.3 in period two (p=0.862); it
      decreased from 1.5 to 0.9 for children born at term, was stable for preterm
      births, but increased from 33.7 to 114.6 for very preterm births (p=0.002).
      Concurrently, neonatal and infant mortality rates decreased in Iceland. The
      proportion of children born preterm increased over time (p=0.002), whereas
      improvements in gross motor function assessed with the Gross Motor Function
      Classification System were confined to term births (p=0.009). The proportion of
      children with diplegia increased, accompanied by a decrease in the proportion
      with quadriplegia (p=0.047). Furthermore, among term births there was a
      significant reduction over time in the proportion of children with epilepsy
      (p=0.030) and in the proportion with two or more associated impairments
      (p=0.030). INTERPRETATION: Although CP prevalence remained stable over 14 years,
      we observed a decrease in prevalence and severity of the disability among term
      births.

PMID- 19388147
TI  - Detection of oxidized methionine in selected proteins, cellular extracts and 
      blood serums by novel anti-methionine sulfoxide antibodies.
AB  - Methionine sulfoxide (MetO) is a common posttranslational modification to
      proteins occurring in vivo.These modifications are prevalent when reactive oxygen
      species levels are increased. To enable the detection of MetO in pure and
      extracted proteins from various sources, we have developed novel antibodies that
      can recognize MetO-proteins. These antibodies are polyclonal antibodies raised
      against an oxidized methionine-rich zein protein (MetO-DZS18) that are shown to
      recognize methionine oxidation in pure proteins and mouse and yeast extracts.
      Furthermore, mouse serum albumin and immunoglobulin (IgG)were shown to accumulate
      MetO as function of age especially in serums of methionine sulfoxide reductase A
      knockout mice. Interestingly, high levels of methionine-oxidized IgG in serums of
      subjects diagnosed with Alzheimer's disease were detected by western blot
      analysis using these antibodies. It is suggested that anti-MetO-DZS18 antibodies
      can be applied in the identification of proteins that undergo methionine
      oxidation under oxidative stress, aging, or disease state conditions.

PMID- 19388149
TI  - Roles of ERK, PI3 kinase, and PLC-gamma pathways induced by overexpression of
      translationally controlled tumor protein in HeLa cells.
AB  - We reported previously that translationally controlled tumor protein (TCTP) is a
      cytoplasmic repressor of Na,K-ATPase in HeLa cells. In the current study, we
      showed that TCTP overexpression using adenovirus as vehicle, induced partial
      inhibition of Na,K-ATPase; phosphorylation of EGFR tyrosine residues 845,
      992,1068, and 1148; activation of Ras/Raf/ERK pathway; activation of PI3K/Akt
      pathway; and phosphorylation of PLC-gamma in HeLa cells. Specific inhibition of
      PI3K/Akt pathway in contrast to the inhibition of ERK,significantly decreased
      TCTP overexpression-induced survival signal. Inhibition of PLC-gamma pathway
      significantly decreased TCTP overexpression-induced cell migration but inhibition
      of ERK had less effect. These results suggest that TCTP plays a key physiological
      role in cell survival through Akt pathway and migration through PLC-gamma
      pathway.

PMID- 19388150
TI  - Guanidinoacetate methyltransferase (GAMT) deficiency: late  onset of movement
      disorder and preserved expressive language.
AB  - Guanidinoacetate methyltransferase (GAMT) deficiency is a disorder of creatine
      biosynthesis, characterized by early-onset learning disability and epilepsy in
      most affected children. Severe expressive language delay is a constant feature
      even in the mildest clinical phenotypes.We report the clinical, biochemical,
      imaging, and treatment data of two female siblings (18y and 13y) with an unusual
      phenotype of GAMT deficiency. The oldest sibling had subacute onset of a movement
      disorder at age 17 years, later than has been previously reported. The younger
      sibling had better language skills than previously described in this disorder.
      After treatment with creatine, arginine restriction and ornithine-supplemented
      diet, seizure severity and movement disorder were reduced but cognition did not
      improve. This report confirms that GAMT deficiency, a heterogeneous, potentially
      treatable disorder, detected by increased levels of guanidinoacetate in body
      fluids (e.g. plasma or urine) or by an abnormal creatine peak on magnetic
      resonance spectroscopy, should be considered in patients of any age with
      unexplained, apparently static learning disability and epilepsy.

PMID- 19388151
TI  - Neuromuscular hip dysplasia in Charcot-Marie-Tooth disease  type 1A.
AB  - Charcot-Marie-Tooth disease (CMT) is one of the most common inherited
      neurological disorders, affecting 36 in 100,000 people. CMT type 1A (hereditary
      motor and sensory neuropathy) is the most frequent form of this disease,
      affecting 60 to 80% of the CMT population, but its diagnosis may be delayed
      because of inconsistent clinical signs and symptoms and a considerable
      variability in age at onset. Here, we report on four children (aged 10-17y) who
      presented with neuromuscular hip dysplasia and other orthopedic abnormalities but
      were only later diagnosed with CMT 1A. Hip dysplasia may be the initial clinical
      sign in CMT, so children with late-manifesting hip disease (i.e. age >8y) should
      be examined for signs of peripheral neuropathy, particularly when presenting with
      a 'waddling' or broad-based gait.

PMID- 19388152
TI  - Seizures in the intrahippocampal kainic  acid epilepsy model: characterization
      using  long-term video-EEG monitoring in the rat.
AB  - OBJECTIVE: Intrahippocampal injection of kainic acid (KA) in rats evokes a status
      epilepticus (SE) and leads to spontaneous seizures. However to date, precise
      electroencephalographic (EEG) and clinical characterization of spontaneous
      seizures in this epilepsy model using long-term video-EEG monitoring has not been
      performed. MATERIALS AND METHODS: Rats were implanted with bipolar hippocampal
      depth electrodes and a cannula for the injection of KA (0.4 lg /0.2 ll) in the
      right hippocampus. Video-EEG monitoring was used to determine habitual parameters
      of spontaneous seizures such as seizure frequency, severity, progression and day
      night rhythms. RESULTS: Spontaneous seizures were detected in all rats with 13
      out of 15 animals displaying seizures during the first eight weeks after SE. A
      considerable fraction (35%) of the spontaneous seizures did not generalize
      secondarily. Seizure frequency was quite variable and the majority of the KA
      treated animals had less than one seizure per day. A circadian rhythm was
      observed in all rats that showed sufficient seizures per day. CONCLUSIONS: This
      study shows that the characteristics of spontaneous seizures in the
      intrahippocampal KA model display many similarities to other SE models and human
      temporal lobe epilepsy.

PMID- 19388153
TI  - Augmented heme oxygenase-1 expression in areca quid chewing-associated oral
      submucous fibrosis.
AB  - OBJECTIVES: Heme oxygenase-1 (HO-1) is known as a stress-inducible protein and
      functions as an antioxidant enzyme. HO-1 is consistently and dramatically
      upregulated in a variety of fibrotic diseases. The aim of this study was to
      compare HO-1 expression in normal human buccal mucosa and oral submucous fibrosis
      (OSF) specimens and further explore the potential mechanism that may lead to
      induce HO-1 expression. METHODS: Twenty OSF specimens and 10 normal buccal mucosa
      were examined by immunohistochemistry. The mRNA levels of HO-1 from fibroblasts
      cultured from OSF and normal buccal mucosa fibroblasts (BMFs) were evaluated by
      reverse transcription polymerase chain reaction. The effect of arecoline, the
      major areca nut alkaloid, was added to explore the potential mechanism that may
      lead to induce HO-1 expression. RESULTS: Heme oxygenase-1 expression was
      significantly higher in OSF specimens (P < 0.05) and expressed mainly by
      fibroblasts, endothelial cells, and inflammatory cells. OSF demonstrated
      significantly higher HO-1 mRNA expression than BMFs (P < 0.05). Arecoline was
      also found to elevate HO-1 mRNA and protein expression in a dose-dependent manner
      (P < 0.05). CONCLUSIONS: Taken together, the data presented here demonstrated
      that HO-1 expression is significantly upregulated in OSF from areca quid chewers,
      and arecoline may be responsible for the enhanced HO-1 expression in vivo.

PMID- 19388154
TI  - Retraction notice to "The retinoic acid receptor/CaMKII interaction:
      pharmacologic inhibition of CaMKII enhances the differentiation of myeloid
      leukemia cells" [Blood Cells Mol. Dis. 39 (2007) 307-315].

PMID- 19388155
TI  - Social enterprise.

PMID- 19388156
TI  - Rediscovering complement, the first barrier of innate immunity.

PMID- 19388157
TI  - Inherited complement deficiencies and bacterial infections.
AB  - A wide variety of bacteria are recognized by the complement system through the
      early components that trigger the three pathways of complement activation,
      leading to the release of biologically active products involved in opsonization,
      recruitment of phagocytes and bacterial killing. Deficiencies of complement
      components and regulators provide a model to understand the in vivo role of
      complement as a defense system against bacterial infections. An increased
      susceptibility to these types of infections is frequently seen in individuals
      with C2, C3, late component, properdin and factor I deficiencies. The
      identification of these deficiencies is essential for the adoption of preventive
      measures aimed to reduce the risk of bacterial infections. Vaccination represents
      the treatment of choice to protect these subjects, although further studies on a
      large number of C-deficient individuals are needed to prove the protective effect
      of vaccines.

PMID- 19388158
TI  - Complement factor H related proteins in immune diseases.
AB  - The complement system is a powerful part of the host innate immune defense and is
      aimed to damage and eliminate microbes and modified self-cells. To protect host
      cells and biological surfaces from damage mediated by complement activation
      products a tight control of the complement system is necessary. Imbalances in
      complement regulation contribute to tissue injury and can result in autoimmune
      diseases such as hemolytic uremic syndrome (HUS), membranoproliferative
      glomerulonephritis (MPGN) or age related macular degeneration (AMD). Disease
      associated mutations have been identified in several complement regulators or
      components, such as members of the factor H protein family. This group includes
      the major alternative pathway regulator, complement factor H (CFH) and five
      complement factor H related proteins (CFHR). Homozygous chromosomal deletion of a
      genomic 84 kb, chromosomal fragment which includes the genes CFHR1/CFHR3 is a
      risk factor for hemolytic uremic syndrome (HUS) at young age and is predominantly
      associated with the generation of autoantibodies to CFH, leading to a specific
      type of HUS, called DEAP (deficiency of CFHR and autoantibody positive)-HUS. The
      same deletion however is protective to the development of age related macular
      degeneration (AMD) in elderly people. Thus CFHR1 and CFHR3 proteins, and likely
      also the other members of this gene family are linked to human diseases. We here
      summarize the current knowledge about the role or association of CFHR1 and CFHR3
      in the human diseases HUS and AMD.

PMID- 19388160
TI  - Inhibiting complement activation on cells at the step of C3 cleavage.
AB  - Nearly half of the proteins in the complement system serve in regulation. Control
      at the central step of C3 activation is provided by an orchestrated interplay of
      membrane and plasma regulators. A model system employing Chinese hamster ovary
      (CHO) cells transfected with human regulators was employed to assist in making
      functional comparisons. Also, in this experimental setup, the pathway and
      magnitude of complement activation can be varied while monitoring C4b/C3b
      deposition and cleavage as well as cytotoxicity. This review describes lessons
      learned and the application of this model for functionally characterizing
      mutations in regulators associated with atypical hemolytic uremic syndrome.

PMID- 19388159
TI  - Discrimination between host and pathogens by the complement system.
AB  - Pathogen-specific complement activation requires direct recognition of pathogens
      and/or the absence of complement control mechanisms on their surfaces. Antibodies
      direct complement activation to potential pathogens recognized by the cellular
      innate and adaptive immune systems. Similarly, the plasma proteins MBL and
      ficolins direct activation to microorganisms expressing common carbohydrate
      structures. The absence of complement control proteins permits amplification of
      complement by the alternative pathway on any unprotected surface. The importance
      of complement recognition molecules (MBL, ficolins, factor H, C3, C1q, properdin,
      and others) to human disease are becoming clear as analysis of genetic data and
      knock out animals reveals links between complement proteins and specific
      diseases.

PMID- 19388161
TI  - Complement and humoral immunity.
AB  - The complement system was discovered almost a century ago as an important
      effector in antibody-dependent killing of microorganisms. Since this early period
      much was learned aboutthe biochemistry and structure of complement proteins and
      their function in mediating inflammation. More recently, a prominent role for
      complement was identified in linkage of innate and adaptive immunity. In this
      review, I will discuss our current understanding of the importance of complement
      in enhancing the humoral immune response to both model antigens and pathogens. As
      discussed below, it is evident that the complement system participates in marking
      of "foreign" pathogens and "presenting" them to B cells in a manner that enhances
      both antibody production and long-term memory. In this special issue of Vaccine,
      we see examples of how complement is critical in the immune response to bacterial
      and viral pathogens. Moreover, the finding that most organisms have co-evolved
      proteins to evade complement detection underscores its importance in host
      protection.

PMID- 19388162
TI  - Mechanisms in Neisseria meningitidis for resistance against complement-mediated
      killing.
AB  - Bacterial meningitis and septicaemia is a global health problem often caused by
      Neisseria meningitidis. The complement system is the most important aspect of
      host defence against this pathogen, and the critical interaction between the two
      is influenced by genetic polymorphisms on both the bacterial and the host side;
      variations of the meningococcus may lead to increased survival in human sera,
      whereas humans with complement deficiencies are more susceptible to meningococcal
      infections. Here we discuss the mechanisms of meningococcal resistance against
      complement-mediated killing and the influence of both bacterial and host genetic
      factors.

PMID- 19388164
TI  - Factor H-binding protein, a unique meningococcal vaccine antigen.
AB  - GNA1870, also named factor H-binding protein (fHbp) or rLP-2086, is a genome
      derived antigen and one of the components of a rationally designed vaccine
      against Neisseria meningitidis serogroup B, which has entered phase III clinical
      trials. It has been classified into three main non-cross-protective variant
      groups. GNA1870 has also been termed fHbp because of its ability to bind factor
      H, a key regulatory component of the alternative complement pathway. fHbp is
      important for survival in human blood, human sera, and in presence of
      antimicrobial peptides, independently of its expression level. All these
      properties make fHbp a unique vaccine antigen.

PMID- 19388163
TI  - Factor H and neisserial pathogenesis.
AB  - Both Neisseria gonorrhoeae and N. meningitidis bind to factor H which enhances
      their ability to evade complement-dependent killing. While porin is the ligand
      for human fH on gonococci, meningococci use a lipoprotein called factor H binding
      protein (fHbp) to bind to factor H and enhance their ability to evade complement
      dependent killing. This protein is currently being intensively investigated as a
      meningococcal vaccine candidate antigen. Consistent with the observation that
      meningococci cause natural infection only in humans, the organism resists human
      complement, and are more readily killed by complement from lower animals. This
      human species-specific complement evasion has important implications for
      evaluation of vaccine-elicited antibodies using non-human complement sources and
      development of animal models of disease.

PMID- 19388165
TI  - Contribution of interactions between complement inhibitor C4b-binding protein and
      pathogens to their ability to establish infection with particular emphasis on
      Neisseria gonorrhoeae.
AB  - Complement activation and resulting opsonisation with C3b form key arms of the
      innate immune defense against infections. However, a wide variety of pathogens
      subvert complement attack by binding host complement inhibitors, which results in
      diminished opsonophagocytosis and killing of bacteria by lysis. Human C4b-binding
      protein (C4BP) binds Neisseria gonorrhoeae and Streptococcus pyogenes, both
      uniquely human pathogens. This binding specificity is circumvented by other
      bacterial species, which bind C4BP from numerous mammalian hosts that they
      infect. Binding of C4BP to Neisseria is mediated by outer membrane porin proteins
      and appears to be one of the main factors mediating serum resistance. Targeting
      C4BP binding sites on bacterial surfaces with vaccine-induced antibodies may
      block binding of C4BP and enhance a common vaccine design strategy that depends
      on the generation of complement-dependent bactericidal and opsonophagocytic
      antibody activities.

PMID- 19388166
TI  - The role of complement in gonococcal infection of cervical epithelia.
AB  - Neisseria gonorrhoeae is an exclusive human pathogen that causes the sexually
      transmitted disease, gonorrhea. The gonococcus has developed an exquisite
      repertoire of mechanisms by which it is able to evade host innate and adaptive
      immune responses. Our previous data indicate that the predominately asymptomatic
      nature ofgonococcal cervicitis may, in part, be attributed to the ability of
      these bacteria to subvert the normal function of complement to promote cervical
      disease. Herein we describe the interaction of N. gonorrhoeae with the complement
      alternative pathway with a particular focus on the importance of this interaction
      in promoting gonococcal cervicitis.

PMID- 19388167
TI  - Species-specificity of Neisseria gonorrhoeae infection: do human complement
      regulators contribute?
AB  - Neisseria gonorrhoeae is the causative agent of gonorrhea, a disease restricted
      to humans. Complement forms a key arm of the innate immune system that combats
      gonococcal infections. N. gonorrhoeae uses its outer membrane porin (Por)
      molecules to bind complement down-regulatory proteins, C4b-binding protein (C4BP)
      and factor H (fH), to evade killing by human complement. In addition, sialylation
      of gonococcal lipooligosaccharide (LOS) also enables N. gonorrhoeae to bind fH.
      Strains of N. gonorrhoeae that resist killing by human serum complement are
      killed by serum from rodent, lagomorph and primate species, which cannot be
      readily infected experimentally with this organism and whose C4BP and/or fH
      molecules do not bind toN. gonorrhoeae. Serum resistance of gonococci is restored
      in these sera by human C4BP and/or fH. Direct binding specificity of human and
      chimpanzee C4BP and human fH to gonococci may explain, in part, species-specific
      restriction of natural gonococcal infection and address why Por1B, but not Por1A
      containing gonococcal strains, have been successful in experimental chimpanzee
      infection. Our findings may help to improve animal models for gonorrhea while
      also having implications in the choice of complement sources to evaluate
      neisserial vaccine candidates.

PMID- 19388168
TI  - The complement fitness factor H: role in human diseases and for immune escape of
      pathogens, like pneumococci.
AB  - Factor H is the central regulator of the alternative complement pathway and
      controls early activation of the complement cascade at the level of the C3
      convertase. Mutations in the Factor H gene are associated with severe and diverse
      diseases including the rare renal disorders hemolytic uremic syndrome (HUS) and
      membranoproliferative glomerulonephritis (MPGN) also termed dense deposit disease
      (DDD), as well as the more frequent retinal disease age related macular
      degeneration (AMD). In addition, pathogenic microbes utilize host complement
      Factor H for immune evasion and these pathogens express specific surface
      receptors which bind host innate immune regulators. Sequence variations or
      mutations of one single gene, coding for the host regulator Factor H, form the
      basis for multiple, different disorders such as human renal and retinal diseases
      as well as infections. This association of Factor H but also of additional
      related complement components and regulators with the same diseases demonstrate
      an important role of complement, particularly of the alternative pathway, for
      tissue homeostasis. Disturbances of this central immune surveillance system lead
      to damage of autologous tissues and surfaces and result in autoimmune diseases.
      Remarkably, pathogenic microbes copy this mechanism of immune surveillance: they
      mimic the composition of host cell's, bind Factor H to their surface and engage
      acquired host Factor H for immune disguise.

PMID- 19388169
TI  - Binding of complement regulatory proteins to group A Streptococcus.
AB  - Streptococcus pyogenes or Group A Streptococcus (GAS) is the etiologic agent of
      important human infections such as acute pharyngitis, impetigo, rheumatic fever
      and the streptococcal toxic shock syndrome. Binding of the complement regulatory
      proteins factor H, factor H-like protein 1 (FHL-1), C4b-binding protein (C4BP),
      or CD46 is a crucial step in the pathogenesis of these infections. M protein is
      the GAS protein that generally mediates these interactions. However, a detailed
      analysis of the reports that have investigated the binding of complement
      regulatory components to GAS indicates that this microorganism has evolved
      alternative mechanisms for the recruitment of complement regulatory proteins to
      the bacterial surface. This article summarizes these data to provide a starting
      point for future research aimed at the characterization of additional mechanisms
      developed by GAS to evade the immune system.

PMID- 19388170
TI  - Complement and antibodies: a dangerous liaison in HIV infection?
AB  - Due to ongoing recombination and mutations, HIV permanently escapes from
      neutralizing antibody (nAb) responses of the host. By the masking of epitopes or
      shedding of gp120, HIV-1 further impedes an efficient neutralization by Abs.
      Therefore, nAbs responses of the host are chasing behind a rapidly evolving virus
      and mainly non-neutralizing antibodies (non-nAbs) are present in the host. At the
      same time, complement deposition on immune-complexed HIV may counteract the
      immune response by enhancing the infection. On the other hand, complement
      mediated lysis is a putative effector mechanism to control viral replication.
      Here we review the complex interplay between complement, neutralizing and non
      neutralizing Abs during HIV infection and discuss the contribution of Abs and
      complement in blocking versus enhancing the course of infection.

PMID- 19388171
TI  - Complement and natural antibody are required in the long-term memory response to
      influenza virus.
AB  - Complement, complement receptors and natural antibody (IgM) are important factors
      in the immune response against pathogens. Previous studies have indicated a role
      for C3, the complement receptors CD35/CD21 (CR1/CR2), and IgM in the immune
      response to influenza virus. Nevertheless, their contribution to the long-term
      memory response to this pathogen remains unknown. To elucidate this role, we
      characterized the secondary response on mice deficient of CR1/CR2 (Cr2-/-), C3
      (C3-/-), secreted IgM (micros-/-) and the double knockout C3-/-micros-/-.
      Overall, our results suggest that C3, IgM and CR1/CR2 play crucial roles in the
      maintenance of long-term memory to influenza virus, possibly through the
      development of memory B cells and long-term antibody secretion.

PMID- 19388172
TI  - Herpes simplex virus as a tool to define the role of complement in the immune
      response to peripheral infection.
AB  - A complex network of interactions exist between the innate and adaptive immune
      pathways, which act together to elicit a broad and durable host response
      following pathogen infection. The importance of the complement system in the
      host's defense against viruses has become increasingly clear as a result of
      detailed studies using transgenic mouse models that disrupt specific components
      of this host immune mechanism. We have utilized herpes simplex virus and
      replication-defective mutant strains to examine the impact of the complement
      system on development and maintenance of humoral immune responses. Here we review
      work from our group and others that highlights the central role that complement
      proteins C3 and C4 and complement receptors Cr1/Cr2 play during viral infection.
      We discuss the implications of these results in the context of pathogen infection
      and current vaccine strategies.

PMID- 19388174
TI  - The iC3b receptor of Candida albicans and its roles in pathogenesis.
AB  - On the basis of biochemical and immunologic studies, a receptor for iC3b with
      some activities reminiscent of the integrins CD11b and CD11c was defined on the
      cell wall of clinical and laboratory isolates of Candida albicans. The INT1 gene
      encodes a protein of 1659 amino acids; the Int1 protein participates in adhesion
      to epithelial cells in vitro and in vivo. Int1 is essential for hyphal
      morphogenesis and virulence in a murine model. Recent evidence points to the
      amino terminus of Int1 as the source of a peptide, Pep263, with superantigen-like
      activities.

PMID- 19388175
TI  - Microbial complement inhibitors as vaccines.
AB  - Complement inhibiting surface proteins of pathogenic bacteria provide candidates
      for vaccines because of two reasons. First, an immune response against them would
      recognize the microbes and secondly, it would neutralize the key bacterial
      virulence mechanism. Prerequisites for a vaccine protein include the following:
      (i) it should show limited variability, (ii) it should be immunogenic and the
      immune response against it should cover a sufficiently broad range of microbial
      strains, (iii) it should not be hidden beneath a capsule, long LPS O
      polysaccharide side chains or a protein coat and (iv) it should not raise
      unwanted immune responses against host structures. Bacterial complement
      inhibitors often act by binding the soluble inhibitors factor H or C4 bp, by
      blocking C3 or C5 activation or by enzymatically cleaving key complement
      components. Inhibitors have been found from all major types of pathogens and may
      offer promise as rational vaccine candidates for preventing diseases such as
      meningococcal meningitis, systemic pneumococcal or group B streptococcal disease
      and Lyme borreliosis.

PMID- 19388176
TI  - [Low-traumatic approach in secondary surgery on the aortic valve].
AB  - The possibility of a second operation on the aortic valve and root using a
      minimally invasive approach is considered along with discussion of its
      traumaticity and peculiarities of the postoperative period.

PMID- 19388173
TI  - Complement and its role in protection and pathogenesis of flavivirus infections.
AB  - The complement system is a family of serum and cell surface proteins that
      recognize pathogen-associated molecular patterns, altered-self ligands, and
      immune complexes. Activation of the complement cascade triggers several antiviral
      functions including pathogen opsonization and/or lysis, and priming of adaptive
      immune responses. In this review, we will examine the role of complement
      activation in protection and/or pathogenesis against infection by Flaviviruses,
      with an emphasis on experiments with West Nile and Dengue viruses.

PMID- 19388177
TI  - [Computerized tomography in the diagnosis of congenital heart disease].
AB  - The aim of the work was to evaluate the possibility to use CT techniques (SCT and
      MRT) for the diagnosis of congenital heart disease. A total of 426 patient aged 0
      54 years were examined (171 by MRT and 255 by SCT. SCT of the heart with bolus
      injection of a contrast medium was performed on an Evolution C-150 superfast
      tomograph in the step-scanning regime and prospective synchronization with ECG
      (slice thickness 1.5-3 mm). Fasting SCT was used to examine children in the first
      year of life during quiet (unforced) breathing. Contrast material (Omnipack-300,
      350; Visipack-270, 320) was administered at a dose of 1.5-2.0 ml/ kg b.w. at 0.2
      0.6 ml/s. MRT was performed using a conventional MR tomograph with a 1 T field
      and pulsed spin-echo sequences synchronized with ECG for obtaining the anatomic
      picture and gradient echo-signals (cine-MRT) for the assessment of functional
      parameters (slice thickness 4-7 mm). Babies were examined under medicamentous
      sedation. All images were treated and analysed using an Advantage Windows 2.0
      workstation and a program package for heart image analysis. A rational procedure
      of CT and image analysis was developed in the course of the study. It provided
      data on the formation of all segments and intercommunications of the heart,
      mutual localization of its cavities and major vessels, permitted to perform
      morphometry of selected cardiac structures and detect anatomic defects. The
      informative and diagnostic value of methods for comprehensive evaluation of the
      heart and mediastinum in patients with congenital heart disease was assessed.
      Methods of choice for the diagnosis of abnormalities and follow-up of the
      patients in different periods after surgery were identified.

PMID- 19388178
TI  - Prevalence of oral pathologic findings in an ancient pre-Columbian archeological
      site in the Atacama Desert.
AB  - OBJECTIVE: To determine the prevalence of oral pathologic findings in an ancient
      culture that inhabited the Atacama Desert. MATERIALS AND METHODS: A systematic
      examination was performed on the remains of 83 individuals unearthed from a
      prehistoric burial ground. A total of 57 skeletal remains achieved appropriate
      inclusion criteria, from which estimated age at death, gender, ante- and
      postmortem tooth loss, prevalence and location of caries, apical periodontitis
      sequela, alveolar bone resorption and attrition were recorded. RESULTS: From the
      analyzed skeletal remains (13 male, 22 female and 22 not identifiable), the mean
      age estimated was 29.9 +/- 13.8 years. A total of 89.4% of them presented
      permanent dentition with a mean ante-mortem tooth loss of 9.0 teeth and a
      postmortem mean tooth loss of 14.4 teeth per subject. In all, 46.4% of the
      postmortem remaining permanent teeth (n = 237) showed caries lesions.
      Interproximal caries was most frequently observed (31.5%), followed by occlusal
      (25.9%) and cervical caries (19.4%). Root remnants were found in 23.1% of the
      cases. In addition, 58.0% of the adults presented attrition, 26.0% signs of
      apical periodontitis and 44.0% loss of alveolar bone support >5 mm. CONCLUSION:
      The remains of jaws and teeth of the individuals examined in this study presented
      sequelae of severe oral health damage due to caries and periodontal disease.

PMID- 19388179
TI  - CROI 2009: a few key presentations on antiretroviral therapy.

PMID- 19388180
TI  - HIV-related lipodystrophy in Africa and Asia.

PMID- 19388181
TI  - Johnson & Johnson seeks full FDA approval for Intelence.

PMID- 19388183
TI  - Images in HIV/AIDS. HIV and myelodysplasia.

PMID- 19388182
TI  - HSV-1 encephalitis complicated by cerebral hemorrhage in an HIV-positive person.
AB  - Although herpes simplex virus type 1 (HSV-1) is the most common cause of sporadic
      encephalitis in immunocompetent adults, it is an unusual cause of encephalitis in
      patients with HIV/AIDS. We report the case of a 56-year-old man with recently
      diagnosed HIV infection who presented with subacute mental status changes, fever,
      and temporal lobe abnormalities evident on brain imaging. Results of a polymerase
      chain reaction assay of the cerebrospinal fluid were positive for HSV-1. His
      course was complicated by 2 episodes of cerebral hemorrhage. He ultimately
      improved after surgical decompression, treatment with acyclovir, and a switch
      from a protease inhibitor-based antiretroviral regimen to one including an
      integrase inhibitor.

PMID- 19388184
TI  - Select updates from the 16th CROI: treatment-related cardiovascular risk,
      pharmacokinetic issues, and interleukin-2 use.

PMID- 19388185
TI  - [Gardens on paper: the theory and scholarship of gardens in     Spain in the 19th
      century].

PMID- 19388186
TI  - [Educational conference on biological diversity and ecology of parasites in the
      aquatic ecosystem. Conference dedicated to Wincenty Leslawa Wisniewski].

PMID- 19388187
TI  - [A discussion forum on health insurance: the Athenaeum of Madrid conferences,
      1934].

PMID- 19388190
TI  - Abstracts of the 15th Congress on Alternatives to Animal Experimentation, Linz,
      Austria, 2008.

PMID- 19388189
TI  - Isis current bibliography of the history of science and its cultural influences,
      2008.

PMID- 19388191
TI  - [The theory of degeneration and the professionalization of psychiatry in Spain,
      1876-1920].

PMID- 19388192
TI  - [Science and collecting in Cuba in the 19th century].

PMID- 19388193
TI  - [Medical aspects of the alchemical art of Diego de Santiago].

PMID- 19388195
TI  - Abstracts of the 24th National Cardiology Congress, 2008, Istanbul, Turkey.

PMID- 19388194
TI  - [End-century metaphors of biological decline: degeneration and revolution in
      Spanish anarchism, 1872-1914].

PMID- 19388197
TI  - Mobility in Melanesia: bigman bilong circulation.

PMID- 19388198
TI  - Population mobility and the transformation of a village community in northern
      Thailand.

PMID- 19388199
TI  - [Abstracts of the 83rd Annual Meeting of the French Society of Surgical
      Orthopedics and Trauma].

PMID- 19388200
TI  - [Abstracts of the 102nd French Congress of Urology, 19-22 November 2008, Paris,
      France].

PMID- 19388201
TI  - Preface. Nucleic acid and peptide aptamers.

PMID- 19388202
TI  - [Abstracts of the 59th Mexican Congress of Gynecology and Obstetrics, 5-9 October
      2008, Tijuana, Mexico].

PMID- 19388203
TI  - Abstracts of the 44th Annual Meeting of the Argentine Society for Biochemistry
      and Molecular Biology Research, 8-11 November 2008, Villa Carlos Paz, Argentina.

PMID- 19388204
TI  - Cancer incidence in five continents. Volume IX.

PMID- 19388205
TI  - [Proceedings and abstracts of the VIth National Academic Conference on
      Neuroinfections, October 16-18, 2008, Bialystok, Poland].

PMID- 19388206
TI  - Calcium-permeable acid-sensing ion channel in nociceptive plasticity: a new
      target for pain control.
AB  - The development of chronic pain involves increased sensitivity of peripheral
      nociceptors and elevated neuronal activity in many regions of the central nervous
      system. Much of these changes are caused by the amplification of nociceptive
      signals resulting from the modulation and altered expression of specific ion
      channels and receptors in the central and peripheral nervous system.
      Understanding the processes by which these ion channels and receptors are
      regulated and how these mechanisms malfunction may lead to new treatments for
      chronic pain. Here we review the contribution of the Ca2+-permeable acid-sensing
      ion channel (ASIC(Ca)) in the development and persistence of chronic pain, and
      the potential underlying mechanisms. Accumulating evidence suggests that ASIC(Ca)
      represents an attractive new target for developing effective therapies for
      chronic pain.

PMID- 19388207
TI  - Inflammation in Alzheimer's disease: amyloid-beta oligomers trigger innate
      immunity defence via pattern recognition receptors.
AB  - The inflammatory process has a fundamental role in the pathogenesis of
      Alzheimer's disease (AD). Recent studies indicate that inflammation is not merely
      a bystander in neurodegeneration but a powerful pathogenetic force in the disease
      process. Increased production of amyloid-beta peptide species can activate the
      innate immunity system via pattern recognition receptors (PRRs) and evoke
      Alzheimer's pathology. We will focus on the role of innate immunity system of
      brain in the initiation and the propagation of inflammatory process in AD. We
      examine here in detail the significance of amyloid-beta oligomers and fibrils as
      danger-associated molecular patterns (DAMPs) in the activation of a wide array of
      PRRs in glial cells and neurons, such as Toll-like, NOD-like, formyl peptide,
      RAGE and scavenger receptors along with complement and pentraxin systems. We also
      characterize the signaling pathways triggered by different PRRs in evoking
      inflammatory responses. In addition, we will discuss whether AD pathology could
      be the outcome of chronic activation of the innate immunity defence in the brain
      of AD patients.

PMID- 19388208
TI  - Anidulafungin: new drug. Invasive candidiasis: just another echinocandin.

PMID- 19388209
TI  - Eculizumab: new drug. Nocturnal paroxystic haemoglobinuria: fewer transfusions.

PMID- 19388210
TI  - Duloxetine in fibromyalgia: rejection. Marketing authorization rejected and
      rightly so.
AB  - The European marketing authorization committee has ruled against the utilisation
      of duloxetine (Cymbalta) in the treatment of diffuse idiopathic polyalgic
      syndrome, alias fibromyalgia. A coherent position, given this psychotropic drug's
      unfavourable risk-benefit balance.

PMID- 19388211
TI  - Hydroxycarbamide in sickle cell syndrome: new drug. For severe cases only.

PMID- 19388212
TI  - Extracorporeal methoxsalen: new drug. Cutaneous T cell lymphoma: for rare
      patients, but better assessment needed.

PMID- 19388213
TI  - Methadone capsules: new formulation. A long-awaited formulation.

PMID- 19388214
TI  - Peginterferon alfa-2b and ribavirin in chronic hepatitis C relapse: new
      indication. For some patients.
AB  - When patients with chronic hepatitis C relapse after initial treatment with
      interferon alfa plus ribavirin, the peginterferon alfa and ribavirin combination
      can be beneficial.

PMID- 19388215
TI  - [The role of the university in the critical evaluation of biomedical literature].
AB  - British and US surveys document that the time dedicated weekly by physicians to
      the critical evaluation of biomedical journals is limited and should be expanded.
      This in the light of the fact that clinicians increasingly need controlled and
      updated medical information. The critical interest and competence in the
      evaluation of medical literature may be taught at the University. Universities,
      and in particular Medical Schools, include, among their tasks, education,
      research and health care. A modern and effective education in the critical
      analysis of biomedical journals should represent an important methodological
      feature of Medical Schools, given that it can constitute an instrument for the
      reasoned analysis of the profile of biomedical research and for the synthesis and
      incorporation of research results into daily clinical practice.

PMID- 19388216
TI  - [How to read medical journals. From ad hoc perusal to proactive reading to keep
      abreast of newly emerging evidence].
AB  - Physicians cannot practice good quality health care without updating their
      knowledge; reading is a key component of the continuing medical education, so
      their reading habits have been frequently studied in the past years. The
      information needs of doctors usually arise during the consultation and they are
      commonly related to the therapeutic and diagnostic strategy. Seeking answers to
      these questions from primary sources, such as medical journals, is time consuming
      and often discouraging. The just-in-time approach should be integrated by a
      "proactive monitoring for newly emerging evidence". Creating such a proactive
      system is not an easy task: time management, triage, teamwork, take home messages
      and tools are the critical steps to a successful lifelong learning. The aim of
      this paper is to help doctors to understand the better management of clinical
      knowledge, and to explain how to keep up professionally with the medical
      literature.

PMID- 19388218
TI  - [Neurofibromatosis type I and hypertension: a case report].
AB  - Pheochromocytomas are catecholamine-producing neuroendocrine tumors arising from
      chromaffine cells derived from the embryonic neural crest. They occur in 0.1-5.7%
      of patients with neurofibromatosis type 1 (von Recklinghausen's disease). We
      report the case of an adrenal pheochromocytoma in a patient with
      neurofibromatosis type 1.

PMID- 19388217
TI  - [Is statin treatment for children safe and effective?].
AB  - The recommendation of statin treatment to younger patients too, as recently
      issued by the American Academy of Pediatrics, appeared to be controversial,
      especially looking at the lack of evidence in term of efficacy on primary end
      point and long term safety data.

PMID- 19388219
TI  - [Abdominal ultrasound features in heart failure].
AB  - Heart failure involves many organs and systems. Because of heart failure is one
      of the most common admission diagnosis in a Medical Ward, we sought their
      abdominal ultrasound features in addition to the cardiac ones.

PMID- 19388220
TI  - [Primary prophylaxis of esophageal variceal bleeding in cirrhotic patients].
AB  - During 2004 and 2005 we selected ten motivated and well informed patients
      affected by hepatic cirrhosis and medium-large esophageal varices; we performed
      endoscopic band ligation to prevent the first bleeding episode in these patients
      because not eligible for non selective beta-blockers full dose therapy. After
      over 3 years' follow-up we have no found fatal or not varices related
      complications. Five patients died from hepatic failure. Recent literature
      highlights endoscopic band ligation usefulness because of favourable cost
      effectiveness ratio and good quality of life in well selected patients treated by
      a skilled endoscopic team.

PMID- 19388221
TI  - [Ethics and evidence-based medicine].

PMID- 19388222
TI  - [Off-label use in oncology. The Italian choice].
AB  - In a context in which there is doubt as to the efficacy and safety of cancer
      drugs recently put on the market, the off-label use of these drugs complicates
      the situation. The Italian government, unlike some others, has opted to lay down
      strict rules regarding off-label use, in order to ensure greater efficacy and
      safety for patients.

PMID- 19388223
TI  - [Cannabinoids in the control of pain].
AB  - Hemp (Cannabis sativa L.) has been used since remotes ages as a herbal remedy.
      Only recently the medical community highlighted the pharmacological scientific
      bases of its effects. The most important active principle, Delta-9
      tetrahydrocannabinol, was identified in the second half of the last century, and
      subsequently two receptors were identified and cloned: CB1 that is primarily
      present in the central nervous system, and CB2 that is present on the cells of
      the immune system. Endogenous ligands, called endocannabinoids, were
      characterized. The anandamide was the first one to be discovered. The
      effectiveness of the cannabinoids in the treatment of nausea and vomit due to
      anti-neoplastic chemotherapy and in the wasting-syndrome during AIDS is
      recognized. Moreover, the cannabinoids are analgesic, and their activity is
      comparable to the weak opioids. Furthermore, parallels exist between opioid and
      cannabinoid receptors, and evidence is accumulating that the two systems
      sometimes may operate synergistically. The interest of the pharmaceutical
      companies led to the production of various drugs, whether synthetic or natural
      derived. The good ratio between the polyunsatured fatty acids omega-3 and omega-6
      of the oil of Cannabis seeds led to reduction of the phlogosis and an improvement
      of the pain symptoms in patients with chronic musculo-skeletal inflammation.

PMID- 19388224
TI  - Antitrust law questioned.

PMID- 19388225
TI  - Loss of licensure as a result of the conviction of a crime.

PMID- 19388226
TI  - My employee has an eating disorder: what can I do to help?

PMID- 19388227
TI  - What does peer review's 'three in five' policy mean?

PMID- 19388228
TI  - Lower your premiums and taxes with a health savings account.

PMID- 19388229
TI  - When the going gets tough: riding out the economic storm.

PMID- 19388230
TI  - If we don't provide a dental home, who will?

PMID- 19388231
TI  - The Points of Light project: doing the best for our kids!

PMID- 19388232
TI  - Michigan's new dental home program for Head Start kids.

PMID- 19388233
TI  - Expanding your patient service through esthetics and hygiene.

PMID- 19388234
TI  - Imaging of the paranasal sinuses and nasal cavity: normal anatomy and clinically
      relevant anatomical variants.
AB  - Anatomy is the foundation on which the understanding of pathological processes in
      radiology is based. This article describes the anatomy of the sinonasal region
      and the clinically relevant anatomical variants, highlighting the need for
      multiplanar reconstructions as a routine part of the examination when reviewing
      this region.

PMID- 19388235
TI  - Sinonasal inflammatory disease.
AB  - Inflammatory sinus disease is ubiquitous. Patients with recurrent or unilateral
      disease and those who do not respond to treatment require imaging. Computed
      tomographic scanning is the mainstay of investigation; magnetic resonance imaging
      is used as a problem-solving tool. The imaging characteristics of sinonasal
      inflammatory conditions are varied. The role of imaging is to identify patterns
      of disease, provide a roadmap for the endoscopist, identify anatomical variants
      that impact on drainage, and exclude aggressive pathology.

PMID- 19388236
TI  - Imaging of sinonasal tumors.
AB  - This article reviews the role of imaging in the diagnosis of sinonasal tumors,
      illustrating the diversity of tumors affecting this region. The symptoms of
      sinonasal tumors are nonspecific; imaging plays a critical role in distinguishing
      benign and malignant disease and may occasionally illustrate characteristic
      radiological features of specific tumors. The patterns of local and distant
      spread of sinonasal malignancy are demonstrated and the respective roles of
      computed tomography and magnetic resonance imaging are explained. Critical
      imaging review areas are discussed together with accurate staging, including
      orbital and intracranial involvement, which determine the appropriate surgical
      approach. The sites and patterns of tumor recurrence and the imaging features of
      recurrent tumor are also discussed.

PMID- 19388237
TI  - Differential diagnosis in sinonasal disease.
AB  - This article summarizes the imaging features that aid in distinguishing
      inflammatory from neoplastic disease and benign from malignant conditions.
      Diagnostic pitfalls are highlighted.

PMID- 19388238
TI  - Dr. Gary Umeda. Ready to be up front & center. Interview by Sandy Kanemura.

PMID- 19388239
TI  - Risk factors & screening modalities for oral cancer.
AB  - Dentists are at the forefront for screening oral cancer. In addition to the well
      known carcinogenic potential of tobacco and alcohol, betel nut chewing and human
      papilloma virus are important risk factors in the development of oral cancer. To
      aid in screening and decreasing morbidity and mortality from oral cancer, a
      variety of techniques have been developed. These techniques show promise but they
      require additional investigations to determine their usefulness in oral cancer
      detection. Dentists need to be well educated and vigilant when dealing with all
      patients they encounter. Early detection, diagnosis and treatment are critical
      for the effective management of oral cancers.

PMID- 19388240
TI  - Can your company survive a disaster?

PMID- 19388241
TI  - Are you prepared for the worst?

PMID- 19388243
TI  - The economic crisis & your practice transition.

PMID- 19388242
TI  - U.S.S. Missouri memorial buoyed by Dental Samaritans' support.

PMID- 19388244
TI  - Improving cash flow in a down economy. How HIM can help reduce denials.
AB  - Maybe HIM professionals can't ease tight credit or reduce bad debt, but they can
      make sure their organizations get full, correct reimbursement on the first
      submission. HIM professionals help improve cash flow by contributing to revenue
      cycle management n these tough economic times-when increases in bad

PMID- 19388245
TI  - HIM breakup. Changing times pull HIM and coding apart.
AB  - Benefits can follow when coding packs its bags and moves to the revenue cycle.
      But all realignments have their opportunities and risks.

PMID- 19388246
TI  - Virtual HIM. Considering the transition to remote departments.
AB  - Health IT is untethering HIM departments from the organization's four walls. The
      benefits are there, but the change affects nearly every HIM operation.

PMID- 19388247
TI  - Street Smart. Understanding the context of emergency medical services
      communication and documentation.
AB  - HIM professionals can expand their understanding of the healthcare continuum by
      becoming more familiar with hospital emergency care and documentation.

PMID- 19388248
TI  - Driving compliance through data governance.

PMID- 19388249
TI  - An OASIS for access management.

PMID- 19388250
TI  - Integrating IT systems strengthens the revenue cycle.

PMID- 19388251
TI  - Health IT certification developments. CCHIT's current work and how to get
      involved.

PMID- 19388252
TI  - Starting a consulting business (updated).

PMID- 19388253
TI  - A new approach to neonatal hyperbilirubinemia.

PMID- 19388254
TI  - Key issues in the 2009 OPPS final rule.

PMID- 19388255
TI  - Streamlining the revenue cycle management process.

PMID- 19388256
TI  - [Research progress of prediction of bacterial sRNA genes and their targets--a
      review].
AB  - Bacterial sRNAs are a class of non-coding RNAs with 40-500 nucleotides in length.
      Most of them function as posttranscriptional regulation of gene expression
      through binding to the translation initiation region of their target mRNAs. In
      view that prediction of sRNAs and their targets provides support for experimental
      identification, some prediction methods have been developed for both of them in
      recent years. In this review, we firstly gave an overview of methods for
      prediction of sRNA genes, which are classified into three categories, namely,
      comparative genomics-based, transcription units-based and machine learning-based
      prediction methods. Secondly, the methods for sRNA target prediction are
      classified into two types, which are sequence alignment-based method and
      prediction of RNA secondary structure-based method, respectively. Finally, the
      principles, advantages and limitations of each kind of method are discussed, and
      perspectives for prediction methods of sRNA and their targets is pointed out.

PMID- 19388257
TI  - [Progress on molecular biology of trehalose synthase--a review].
AB  - Trehalose synthase inverts maltose into trehalose, and plays a very important
      role in trehalose industrial production. Here we reviewed the recent progress on
      studies of molecular biology including the cloning of trehalose synthase gene,
      gene engineering application, structure and catalytic mechanism and the role of
      the enzyme in vivo.

PMID- 19388258
TI  - [Analysis of projects received and funded in division of microbiology from NSFC
      in 2008].

PMID- 19388259
TI  - [Morphologic changes in the life cycle of Cytophaga hutchinsonii].
AB  - OBJECTIVE: To study the morphological changes of Cytophaga hutchinsonii cell
      during its life circle. METHODS: Cytophaga hutchinsonii cell was observed under
      light microscope, fluorescence microscope and scanning electron microscope. The
      nucleoids in the cell were stained with fluorescent dye Hoechst33342 and examined
      by fluorescence microscopy. RESULTS: We discovered that under starvation
      conditions, the long, flexible rod cell of Cytophaga hutchinsonii would bend and
      turn into circular cell. The circular cell failed to produce carboxymethyl
      cellulase. Some of the circular cells might further wind around and turn into
      tiny spherical cells. The tiny spherical cell similar to the microcyst of
      sporocytophaga could germ into long flexible rods again under certain
      circumstances. When growing cultures to logarithmic phase of cell growth,
      Cytophaga hutchinsonii cell with three nucleoids in it was occasionally observed,
      which indicated that the two strands of DNA might act differently in the
      initiation of DNA replication. CONCLUSION: This is the first detailed description
      of the formation process of circular cell and tiny spherical cell in the life
      circle of Cytophaga hutchinsonii. The result will help to further reveal the
      relation between morphologic change and cellulose degradation ability of the
      strain.

PMID- 19388260
TI  - [Construction of eag deletion mutant of Bacillus anthracis vaccine strain A16R].
AB  - OBJECTIVE: Construction of eag deletion mutant of Bacillus anthracis vaccine
      strain A16R. METHODS: To study the function of the gene eag of Bacillus anthracis
      vaccine strain A16R, according to the sequence of Bacillus anthracis Ames strain,
      we designed primers and constructed a recombinant plasmid by the spectinomycin
      resistance cassette, upstream homologous fragment and downstream homologous
      fragment of eag cloned in tandem in pKSV7. We introduced the recombinant into
      A16R by electroporation and screened the mutant using the principle of homologous
      recombination. We checked the mutant using the PCR and proteomics. RESULTS: We
      constructed the recombinant plasmid successfully and got the eag deletion mutant.
      PCR results showed the gene eag was deleted; SDS PAGE showed evident differences
      between prime strain and mutant strain. Two-dimensional gel electrophoresis
      results displayed three EA1 protein points of prime strain were absent in the
      mutant strain. CONCLUSION: We constructed eag deletion mutant of Bacillus
      anthracis vaccine strain A16R. This research will be helpful to study the
      functions of eag gene and the other important genes of Bacillus anthracis.

PMID- 19388261
TI  - [Molecular identification and functional analysis of Clpxoo, a homologue to the
      nucleotide receptor protein in Xanthomonas oryzae pv. oryzae].
AB  - OBJECTIVE: To better understand the mechanisms of cyclic di-GMP signaling in
      Xanthomonas oryzae pv. oryzae (Xoo),the casual pathogen of bacterial blight of
      rice, molecular identification of Clpxoo. METHODS: A putative signal receptor
      protein was performed through gene cloning, sequencing and deletion analysis.
      RESULTS: Sequence analysis showed Clpxoo was a homologue of Crp and Vfr, the cAMP
      receptor proteins in Escherichia coli and Pseudomonas aeruginosa respectively,
      which had the cNMP-binding domains (CAP_ED) at N terminal and the DNA-binding
      domains (HTH_CRP) at C terminal and is highly conserved in the plant-pathogenic
      Xanthomonas spp. We constructed delta clpxoo through a double crossover
      recombination and validated by PCR assay, delta clpxoo displayed the reduced
      motility and extracellular polysaccharide (EPS) production, and increased
      sensitive to H2O2 toxicity compared with PXO99(A). All these phenotype changes
      could be partly restored through complementation of mutants by introducing
      clpxoo. Moreover, we observed no significant changes in production of
      extracellular cellulase and xylanase in vitro, biofilm formation and induction of
      hypersensitive response (HR) on non-host tobacco in delta clpxoo compared to
      PXO99(A). CONCLUSION: Therefore, Clpxoo played a role as one of the global
      regulator in regulation of flagellar motility, EPS production and H2O2
      resistance.

PMID- 19388262
TI  - [Screening of H+ -ATPase deficient mutant of Lactobacillus delbrueckii subsp.
      bulgaricus].
AB  - OBJECTIVE: We identified a neomycin-resistant mutant with reduced membrane-bound
      H+ -ATPase activity from L. delbrueckii subsp. bulgaricus originated from the
      traditional dairy product to develop a yoghurt starter culture with low post
      acidification capacity. METHODS: API 50 CH identification system and 16s rDNA
      sequence analysis were applied to identify the strain isolated from the
      indigenous yoghurt. Neomycin was used to screen spontaneous neomycin-resistant
      mutants. H+ -ATPase activity and metabolic dynamics were evaluated between the
      parent strain and mutants. RESULTS: One strain was identified as L. delbrueckii
      subsp. bulgaricus by API 50 CH identification system and 16s rDNA sequence
      analysis, coded as KLDS 1.9201. Two mutant strains were mutated from KLDS 1.9201
      and coded as KLDS 1.9201-1, KLDS 1.9201-4. Compared with the parent strain,the H+
      -ATPase activity of the mutants KLDS 1.9201-1 and KLDS 1.9201-4 decreased by 46%
      and 60% respectively. After cultured in MRS broth for 24 h, metabolic efficiency
      of the initial glucose for the parent strain was 65%, the mutants were 41% and
      31%, the lactic acid concentration in the culture for the parent strain was 26
      g/L, the mutants were 18 g/L and 15 g/L respectively. The cell density of the
      mutants was lower than that of the parent strain. CONCLUSION: The mutants of L.
      delbrueckii subsp. bulgaricus with reduced membrane-bound H+ -ATPase activity had
      low growth and acid production, which could be applied to develop yoghurt starter
      culture with lower post-acidification.

PMID- 19388263
TI  - [Breeding of arachidonic acid producing Mortierella sabellina by ultraviolet
      mutation].
AB  - OBJECTIVE: We obtained a new mutant with higher growth rate and high capability
      of producing arachidonic acid after protoplast ultraviolet mutation. METHODS:
      Using dry weight of biomass, microbial total lipid and total arachidonic acid
      production as evaluation index, we determined time of ultraviolet irradiation by
      single factor experiment and measured the content of the arachidonic acid by gas
      chromatography. RESULTS: When the power of viltalight lamp was set at
      20W,exposure distance at 30 cm and exposure time at 80 s, lethality of spores of
      Mortierella isabellina was 76.4%. CONCLUSION: After ultraviolet mutation and
      repeatedly screening, a mutat of Mortierella isabellina YZ-124 whose arachidonic
      acid concentration in biomass was 5.76 times of the control strains was obtained.

PMID- 19388264
TI  - [Co-production of thrombolytic enzyme and gamma-polyglutamic acid by liquid
      culture of Bacillus subtilis SBS].
AB  - OBJECTIVE: To analyze the co-production of thrombolytic enzyme and gamma
      polyglutamic acid by liquid-culture of Bacillus subtilis SBS. METHODS: We used
      Bacillus subtilis SBS to produce thrombolytic enzyme (BTE) and 7-polyglutamic
      acid (gamma-PGA) by liquid fermentation. We conducted orthogonal experiments
      analysis between carbon source and nitrogen source. Then through Fibrin-SDS-PAGE,
      UV spectrum, Infra-Red spectrum and high performance liquid chromatography
      (HPLC), we identified the production. RESULTS: We synthesized gamma-PGA in the
      medium without the addition of L-glutamic acid. Bacillus subtilis SBS was a L
      glutamic acid-independent bacterium. The suitable carbon and nitrogen sources for
      the synthesis of thrombolytic enzyme (BTE) were soluble starch and soybean
      peptone. However,the suitable carbon and nitrogen sources for the synthesis of
      gamma-PGA were sucrose and NH4Cl. CONCLUSION: The yields of both products could
      close to the levels of the single synthesis when the concentrations of sucrose,
      soybean peptone and NH4Cl were 10, 20, 8 g/L respectively, the activity of BTE
      reached 265 +/- 25 IU/mL,and the concentration of gamma-PGA reached 1.183 +/-
      0.015 g/L.

PMID- 19388265
TI  - [Analysis of protein interaction network and function of Staphylococcus aureus].
AB  - OBJECTIVE: Staphylococcus aureus is a member of Gram positive bacteria,but is
      also one of common pathogens that are most difficult to treat. It infects human
      skin, soft tissue, mucous membrane, bone and joint, especially in the nosocomial
      environment. Because studies on Staphylococcus aureus before were largely based
      on a single gene or protein, it is necessary to study this organism from the
      whole genome. METHODS: We used bioinformatics methods including five
      computational methods (phylogenetic profile, gene neighbor method, operon method,
      gene fusion method, interolog) to predict the protein interaction network of
      Staphylococcus aureus. RESULTS: We constructed the protein interaction network of
      Staphylococcus aureus and studied its function. CONCLUSION: Through the network
      analysis, we found that the protein interaction network of Staphylococcus aureus
      was subject to scale-free property and a number of very important proteins, such
      as SA0939, SA0868, rpID. Through the analysis of the important cell wall
      synthesis and signal transduction and regulation local networks, we also found
      some very important proteins. Such information will help us better understand
      pathogenic mechanism and develop new drug targets of Staphylococcus aureus.

PMID- 19388266
TI  - [Screening and molecular identification of phosphate-solubilizing bacteria in
      rhizosphere soils in Hainan ecosystem].
AB  - OBJECTIVE: To know the activities of dissolving Ca3 (PO4)2 and FePO4 of phosphate
      solubilizing bacteria (PSB) isolated from acidic soil in Hainan province in China
      and to screen PSB with high and stable activity (PSBHS). METHODS: Soil samples of
      21 plant species were isolated with nutrient agar, crystal violet-nutrient agar,
      and yeast extract-mantol agar with dilution-plate method. Bacterial
      representative of the predominant morphologically distinct colonies present on
      plates were selected randomly and purified on minimal nutrient agar. First
      screening was done on solid medium with tricalcium phosphate (Ca-P) as the sole P
      source, and after 5 days of cultivation the colonies with phosphate-solubilizing
      zones were selected for further screening. Secondary screening was conducted by
      cultivating the selected colonies in Ca-P liquid medium for 6 days at 32 degrees
      C with shaking of 200 r/min, and PSB capable of solubilizing phosphorus up to
      more than 200 mg/L were selected. The third screening--6-day shaking cultivation
      in Ca-P liquid media--was conducted after 4 successive cycles of transfer-culture
      plus 15 d-storage at 4 degrees C. PSB capable of solubilizing phosphorus up to
      more than 200 mg/L was selected and termed as PSB(HS). Then PSBHS were cultivated
      in FePO4 liquid media for 6 days, and the activity of dissolved phosphorus was
      determined. The 16S rDNA gene sequencing and blast search against the public
      database were used to identified PSBHS. RESULTS: In total 363 bacterial
      representatives were isolated from soil samples,and the following three
      screenings reduced the number of representatives to 126, 45, and 14 respectively.
      The amounts of dissolved phosphorus by 14 PSBHS after 6 days of cultivation in Ca
      P liquid media were up to 201.0 mg/L - 623.3 mg/L, the pH values of media
      decreased to 3.82 - 4.34 from initial 7.0,and the final pH values were found to
      be significantly negatively correlated to the amounts of dissolved phosphorus.
      After 6-day of cultivation in FePO4 liquid media,only a small amount of
      phosphorus (1.6 mg/L - 34.2 mg/L) were solubilized by PSBHS, and the final pH
      values of media decreased to 2.87 - 5.67--also significantly negatively
      correlated to the amounts of dissolved phosphorus. The 16S rDNA gene sequencing
      analysis identified 6 PSBHS to be Acinetobacter, 3 to be Pseudomonas, 3 to be
      Serratia, 2 to be Enterobacter.

PMID- 19388267
TI  - [Construction, safety and immunogenicity analysis of attenuated salmonella
      typhimurium harbouring TGEV DNA vaccine].
AB  - OBJECTIVE: To study the feasibility of using attenuated Salmonella typhimurium as
      carrier for oral immunization of TGEV DNA vaccine. METHODS: The 2.1 Kb fragments
      of the TGVE SC-H strain S gene that encompasses all the four major antigenic
      domains were amplified by RT-PCR and cloned into eukaryotic expression vector
      pVAX1. The recombinant plasmid pVAX-S was transfected into COS7 cellsand the
      expression of recombinant plasmids was identified by indirect immunofluorscence
      assay. Then pVAX-S was transformed by electroporation into attenuated Salmonella
      typhimurium SL7207. The recombinant was screened and designated as SL7207 (pVAX
      S). Mouse peritoneal macrophages were infected with SL7207 (pVAX-S), the
      transcription and expression of S gene were detected by RT-PCR and indirect
      immunofluorscence. BALB/c mouse were inoculated orally with SL7207(pVAX-S) at
      dosage of 5 x 10(8), 1 x 10(9) and 2 x 10(9) CFU for safety analysis. In a
      vaccination test, BALB/c mouse were immunized orally with recombinant bacterium
      at dosage of 1 x 10(9) CFU, for 3 times and specific serum IgG and intestinal
      mucosal IgA antibody were detected by indirect ELISA. RESULTS: Recombinant
      plasmid pVAX-S was constructed correctly and expressed in COS7 cells. The
      transcription and expression of S gene were detected after mouse peritoneal
      macrophages were infected with SL7207 (pVAX-S). The recombinant bacterium was
      safe to mouse at dosage of 2 x 10(9) CFU. Specific serum IgG and intestinal
      mucosal IgA antibody against TGEV S protein were detected in SL7207 (pVAX-S)
      immunized group at 2 weeks post-boosting,and there were significant difference (P
      < 0.05) in serum IgG and most significant difference (P < 0.01) in intestinal
      mucosal IgA at 2 weeks after the third immunization, compared with SL7207(pVAX)
      control group. CONCLUSION: The recombinant Salmonella carrying TGEV S gene DNA
      vaccines had good immunogenicity and safety in mouse.

PMID- 19388268
TI  - [Construction of a recombinant HVT virus expressing the HA gene of avian
      influenza virus H5N1 via Rde/ET recombination system].
AB  - OBJECTIVE: In recent years,manipulation of large herpesvirus genomes has been
      facilitated by using bacterial artificial chromosome (BAC) vectors. We have
      previously reported the construction of the BAC clones (HVT BACs) of herpesvirus
      of turkey (HVT). With these BAC clones in hand,we manipulated the genome of HVT
      by utilizing Red/ET recombination system, and developed a biologically safe live
      vaccine based on the HVT BACs. METHOD: In this two-step approach, we first
      transformed the plasmid pRedET into the DH10B competent cells that carried the
      HVT BACs,and added inducer L-arabinose into the cells. We prepared the cells into
      competent cells and electroporated the linear rpsL-neo counter
      selection/selection cassette flanked by the 50 bp long homology arms into the
      cells. So the functional cassette was inserted into the U(S)2 locus. Only
      colonies carrying the modified BAC would survive Kanamycin selection on the agar
      plates. The successful integration of the rpsL-neo cassette was monitored by PCR
      and Streptomycin selection, for the insertion of rpsL-neo cassette cells will
      become Streptomycin sensitive. Secondly, in the same way, we replaced the rpsL
      neo cassette with the hemagglutinin (HA) gene of (HPAIV) A/Goose/
      Guangdong/1/96(H5N1) flanked by the same homology arms. Only colonies which lost
      the rpsL-neo cassette will grow on Streptomycin containing plates. RESULTS:
      Finally, we obtained many colonies of which the HA gene of the AIV was inserted
      into the U(S)2 locus to be modified of HVT. And we reconstituted one recombinant
      virus from transfecting one of these BAC clones DNA into chick embryo fibroblasts
      (CEFs). CONCLUSION: We achieved one rescued recombinant virus which designated as
      rHVT-HA3. The H5 subtype HA gene expression in this recombinant virus rHVT-HA3
      was confirmed by immunofluorescence assay.

PMID- 19388269
TI  - [Soluble expression of chicken interferon-gamma and antiviral activity of
      purified expression product].
AB  - OBJECTIVE: We cloned and expressed chicken interferon-gamma gene (chIFN-gamma),
      and detected the bioactivity of chIFN-gamma expressed in Escherichia coli (E.
      coli). METHODS: The chIFN-gamma mature protein gene was amplified by RT-PCR from
      spleen lymphocytes of chicken which were stimulated with concanavalin A (ConA)
      and then cloned into the prokaryotic expression vector pET-32a ( + ). Recombinant
      expression plasmid of pET-32a ( + )-chIFN-gamma was constructed and then
      transformed into the competent E. coli BL21 (DE3) cells for expression with IPTG
      induction. Purified soluble rchIFN-gamma proteins were obtained by Ni-NTA His
      Bind Resin affinity chromatography and identified by SDS-PAGE gel and Western
      blot assay. The antiviral activity was detected by MDCK-VSV system. RESULTS: A
      456 bp cDNA encoding chIFN-gamma mature protein gene was cloned and successfully
      expressed in E. coli with approximate molecular weight of 31.0 kDa, which could
      be recognized by anti-His mAb and rabbit polyclonal antibody against chlFN-gamma.
      The recombinant chIFN-gamma proteins were expressed to form inclusion bodies with
      a portion of soluble protein. The soluble rchIFN-gamma proteins were purified by
      Ni-NTA column under a native condition with the yield of 3.0 mg/L. The purified
      recombinant chIFN-gamma (rchIFN-gamma) proteins by 1:32 dilution could resist 100
      TCID50 VSV virus attack. CONCLUSION: The purified rchIFN-gamma proteins by Ni-NTA
      column under a native condition had better antiviral activity, which will
      establish a basis for further developing new type antiviral interferon
      praeparatum.

PMID- 19388270
TI  - [Low temperature oxygen plasma sterilization effect on pseudomonas aeruginosa].
AB  - OBJECTIVE: Low temperature oxygen plasma was used to sterilize the Pseudomonas
      aeruginosa samples on the polyethylene terephthalate (PET) sheets in a self
      designed reactor that included the discharge area, afterglow area and remote
      area. METHODS: Before and after plasma treatment, the cell morphology was studied
      by scanning electron microscopy (SEM). The cell wall or cell membrane cracking
      was testified to determine the content of protein by using coomassie light blue
      technique. Besides, double Langmuir probe and electron spin resonance
      spectroscopy were used to determine the temperature of electrons (ions) and the
      concentration of free radicals, respectively. RESULTS: Under the treatment time
      of 30 s,the germicidal effects were 4.2, 3.8 and 2.6 respectively in the three
      areas. SEM observations showed that the plasma activity cracks the cell wall and
      cell membrane, resulting in cellular content leakage. In addition,the results
      from electron spin resonance spectroscopy and double Langmuir electron probe
      showed that electrons, ions and oxygen free radicals played important roles in
      sterilization in the discharge area, but only oxygen free radicals acted to
      sterilize the bacteria in the afterglow area and the remote area. CONCLUSION: The
      active species can be separated effectively in this reaction equipment, and we
      further elucidated the mechanisms of plasma sterilization in the remote plasma
      field.

PMID- 19388271
TI  - [Simultaneous detection of enterovirus 71 and coxsackievirus A16 by multiplex
      real-time PCR with an internal control].
AB  - OBJECTIVE: To rapidly identify EV71 and CA16 simultaneously. METHODS: A multiplex
      real-time PCR with an internal control (IC) was developed. The specificity,
      sensitivity, reproducibility of the real time RT-PCR assay were estimated and
      more over 400 clinical samples were tested. RESULTS: The results showed 100%
      specificity for the selected panel. The assay met the sensitivity of 50% tissue
      culture infective dose (TCID50) per milliliter samples for CA16 and 0.1 TCID50
      for EV71. Analysis with 10(4) - 0.1 TCID50/mL EV71 or CA16 samples demonstrated
      high reproducibility with a coefficient of variation (CV) of 0.9% - 2.0% for EV71
      and 0.9% - 2.3% for CA16. More than 400 clinical samples were detected by real
      time PCR,The results showed that the average positive ratio for EV71 and CA16
      were 46.1% and 14.2%, higher than common assay (34.5% and 12.8%). Moreover, the
      result statistics indicated that there were PCR inhibition in stools, rectal
      swabs and throat swabs specimens with inhibition ratio from 1.8% to 3.4%. The
      inhibition ratio of these samples showed the importance of IC when PCR was used
      to detect the RNA of EV71, CA16 or other enterovirus. CONCLUSION: As a result of
      its high specificity, sensitivity and avoiding false negative results by using an
      internal control, the assay is suitable for rapid clinical diagnosis of EV71 and
      CA16.

PMID- 19388272
TI  - [Diversity and bioactivity analysis of actinomycetes isolated from grand Shangri
      La soil].
AB  - OBJECTIVE: To obtain new pharmaceuticals and enzymes with high activity,we
      studied the composition as well as antimicrobial and enzyme activities of
      actinomycetes in Grand Shangri-La. METHODS: Using 4 media,we isolated mesophilic
      and psychrophilic actinomycetes from 220 soil samples collected from areas with
      different altitudes in Grand Shangri-La. Twenty-five representative isolates were
      phylogenetically analyzed based on their 16S rRNA gene sequences. Antimicrobial
      activities against four bacteria and seven fungi were tested using agar well
      diffusion method. Genes encoding type I and II polyketide synthases (PKS I, PKS
      II), nonribosomal peptide synthase (NRPS) and polyene cytochrome P450 hydroxylase
      (CYP) were screened by PCR. Furthermore,several enzyme activities of
      psychrophilic actinomycetes were examined. RESULTS: The 25 representative strains
      belonged to 6 suborders, 12 families and 15 genera of the order Actinomycetals.
      For NRPS and CYP genes screening, positive strains were 14 and 11, respectively.
      Among the 111 actinomycetes isolated under low-temperature conditions, 88% were
      psychrotroph strains, 12% were psychrophilic actinomycetes, and most of them
      utilized gelatin, cellulose and chitin. CONCLUSION: Actinomycetes diversity is
      rich in Grand Shangri-la, and has the potential for conservation and utilization
      of actinomycetes resources.

PMID- 19388273
TI  - [Identification and cloning of vip3A genes from isolates of Bacillus
      thuringiensis and their bioactivity analysis].
AB  - OBJECTIVE: To survey the distribution of vip3A-type genes from isolates of
      Bacillus thuringiensis in China and to clone novel vip3A genes encoding Vip3A
      proteins with high insecticidal activity against Lepidopteran insect larvae.
      METHODS: We applied PCR-RFLP method to identify vip3A-type genes from 171
      isolates and cloned novel vip3Aa genes. RESULTS: The vip3A-type genes appeared in
      63 of 117 B. thuringiensis isolates. We cloned 2 novel vip3Aa genes from isolates
      of TF9 and Bt16. Then, we subcloned vip3Aa26 and vip3Aa27 into vector pQE30 and
      transformed into Escherichi coli M15, respectively. The results of SDS-PAGE and
      Western blot analyses showed that an 88 kDa peptide was expressed in E. coli M15
      with 1 mmol/L of IPTG induction at 37 degrees C, respectively. The International
      Nomenclature Committee of Bt nominated these two genes as the novel vip genes of
      vip3Aa26 and vip3Aa27, respectively. The bioassay results indicated that the
      Vip3Aa27 proteins were highly toxic to Trichoplusia ni, Spodoptera exigua and
      Helicoverpa armigera larvae and the LC50 values were 0.1251 microg/mL, 0.238
      microg/mL and 9.238 microg/mL, respectively. However, the Vip3Aa26 protein only
      possessed toxicity to T. ni larvae. CONCLUSIONS: The novel Vip3Aa27 protein had
      higher activity to Lepidopteran insect larvae compared with that for Vip3Aa26
      protein. The results demonstrated that some amino acid changes had remarkable
      effect on the insecticidal activity.

PMID- 19388274
TI  - [Effect of exopolysaccharide from Bifidobacterium bifidum on cell of gastric
      cancer and human telomerase reverse transcriptase].
AB  - OBJECTIVE: To study the inhibition of human gastric cancer cell line BGC-823 by
      exopolysaccharide (B. EPS) extracted from Bifidobacterium bifidum and the effect
      on the activity of telomerase rate-limiting factor human telomerase reverse
      transcriptase (hTERT). METHODS: In vitro human gastric cancer cell line BGC-823
      were treated by three concentrations of B. EPS. The inhibition rate of gastric
      cancer cell line BGC-823, the morphology changes of cells and the apoptosis in
      the initial stage of cell was observed respectively by MTF, inverted fluorescent
      microscope and the Annexin V-FITC/PI flow cytometry. In addition, the effect of
      B. EPS on cell telomerase rate-limiting factor hTERT mRNA was tested by RT-PCR;
      the changes in the concentration of calcium ions inside the cytoplasm were
      detected by spectrofluorometer. RESULTS: B. EPS inhibited the growth of gastric
      cancer cell BGC-823 (P < 0.05), the inhibition rate increased and the
      concentration of B.EPS showed dose-time response relation. The expression of cell
      telomerase rate-limiting factor hTERT mRNA decrease after effected by B.EPS (P <
      0.05), and showed dose-effect relation with B. EPS. The concentration of calcium
      ion in cytoplasm was higher than the control apparently (P < 0.05). CONCLUSION:
      The apoptosis mechanism of human gastric cancer cell line BGC-823 induced by B.
      EPS might be relevant with the changes of the hTERT mRNA expression and the
      calcium ions concentration in cytoplasm.

PMID- 19388275
TI  - [Expressing borna disease virus phosphoprotein in PC-12 cell and its influence on
      the cell proliferation].
AB  - OBJECTIVE: To establish stable expressing system of Borna disease virus (BDV)
      phosphoprotein in PC-12 cells, and then study its influence on cell proliferation
      of PC-12 cells. METHOD: An expression plasmid with green fluorescence protein was
      cloned and identified to express BDV phosphoprotein. Cultured PC-12 cell was
      transfected with the recombinant plasmid by positive ion lipidsome method.
      Fluorescence microscopy was used to detect the expression of phosphoprotein in PC
      12 cells, then G418 was added into cell culture medium to kill cells without
      recombinant plasmid. We performed reverse transcriptase polymerase chain reaction
      (RT-PCR) in the 10th generation of treated cells to examine the expression of BDV
      phosphoprotein. The proliferation of treated cells and control cells was examined
      by methyl thiazolyl tetrazolium assay (MT). RESULT: The recombinant plasmid was
      confirmed to be able to express BDV phosphoprotein and green fluorescence protein
      by both fluorescence microscopy and RT-PCR. BDV phosphoprotein expressed in PC-12
      cell inhibited cell proliferation. CONCLUSION: We established a stable expressing
      system of BDV phosphoprotein in PC-12 cell. This cell model can be used to study
      the effect of BDV phosphoprotein on the centre nervous system without exposure to
      live virus.

PMID- 19388276
TI  - [Culture optimization for protein expression in Escherichia coli].
AB  - OBJECTIVE: We developed a new culture-complex auto-inducing media (CAI) for
      heterogenous protein expression in Escherichia coli. METHODS: To test expression
      efficiency in the CAI, we constructed seven different plasmids named p-1, p-2, p
      3, p-4, p-5, p-6 and p-7. These plasmids were transformed into E. coli BL21, then
      expressed in both Luria-Bertani madia LB and CAI. To improve the expression level
      even more, we analyzed the composition of the CAI and optimized the culture.
      RESULTS: The expression levels of seven fusion proteins in CAI were four times
      higher than those in Luria-Bertani. Through a series of changes we formed a new
      optimized culture (CAI-4). CONCLUSION: Comparing to the expression levels of
      these fusion proteins (P-1, P-2, P-3) in CAI, the expression levels of fusion
      proteins in CAI-4 increased 2-fold.

PMID- 19388277
TI  - [Screening and identification of a single chain antibody fragment].
AB  - OBJECTIVE: To screen and identify anti- Aflatoxin B1 single chain antibodies
      (scFv) from Tomlinson (I) library. METHODS: The phages absorbed on the ELISA
      plate were eluted by four methods including glycine buffer elution, trypsin
      elution, AFB1 competitive elution and competitive elution following trypsin
      treatment. The phage positive clones were transformed into Escherichia coli
      HB2151 and soluble scFv protein was expressed with the induction of Isopropyl
      beta-D-1-Thiogalavtopy ranoside (IPTG). The scFv was identified by ELISA and DNA
      sequence. RESULTS: Comparing the four methods, we found that the most efficient
      way to get positive clones was competitive elution following trypsin treatment.
      Obtainning two positive clones that could bind specifically with free AFB1, which
      their relative affinity were 0.4 microg/mL and 0.7 microg/mL, respectively. DNA
      sequencing results showed that the scFv belonged to human immunoglobulin variable
      region. CONCLUSION: The specific human scFv could be obtained with phage antibody
      library, and our method provided an alternative for screening recombinant
      antibody against anti-hapten.

PMID- 19388278
TI  - Cerebrovascular reactivity and autonomic drive following traumatic brain injury.
AB  - INTRODUCTION: The autonomic nervous system exerts tonic control on cerebral
      vessels, which in turn determine the autoregulation of cerebral blood flow. We
      hypothesize that the impairment of cerebral autoregulation following traumatic
      brain injury might be related to the acute failure of the autonomic system.
      METHODS: This prospective, observational study included patients with severe
      traumatic brain injury requiring mechanical ventilation and invasive monitoring
      of intracranial pressure (ICP) and arterial blood pressure (ABP). Pressure
      reactivity index (PRx), a validated index of cerebrovascular reactivity, was
      continuously monitored using bedside computers. Autonomic drive was assessed by
      means of heart rate variability (HRV) using frequency domain analysis. FINDINGS:
      Eighteen TBI patients were included in the study. Cerebrovascular reactivity
      impairment (PRx above 0.2) and autonomic failure (low spectral power of HRV) are
      significantly and independently associated with fatal outcome (P = 0.032 and P <
      0.001, respectively). We observed a significant correlation between PRx and HRV
      spectral power (P < 0.001). The high frequency component of HRV (HF, 0.15-0.4Hz)
      can be used to predict impaired autoregulation (PRx > 0.2), although sensitivity
      and specificity are low (ROC AUC = 0.67; P = 0.001). CONCLUSION: Following
      traumatic brain injury, autonomic failure and cerebrovascular autoregulation
      impairment are both associated with fatal outcome. Impairment of cerebrovascular
      autoregulation and autonomic drive are interdependent phenomena. With some
      refinements, HRV might become a tool for screening patients at risk for cerebral
      autoregulation derangement following TBI.

PMID- 19388279
TI  - A comparison between the transfer function of ABP to ICP and compensatory reserve
      index in TBI.
AB  - BACKGROUND: The transfer functions which map the arterial blood pressure to the
      intracranial pressure and the compensatory reserve index have been investigated
      by various groups to evaluate the brain compliance of patients with traumatic
      brain injury. The focus of this study has been to assess the capability of both
      the above mentioned methods to monitor the intracranial compliance in patients
      suffering from brain swelling. MATERIALS AND METHODS: Clinical data was collected
      from sixteen traumatic brain injury patients and split into 4 min segments. For
      each segment, both the magnitude of the empirical transfer function at the
      fundamental cardiac frequency and the compensatory reserve index were extracted.
      FINDINGS: The mean values of the compensatory reserve index and the magnitude of
      the transfer function which scored higher than 0.7 and 0.1 respectively were
      recorded for all patients suffering from brain swelling. By comparing the
      histogram of the magnitude of the transfer function at the fundamental cardiac
      frequency with the histogram of the compensatory reserve index for all patients,
      a positive correlation between the mean values and a negative correlation among
      their variances were observed. The linear correlation between the mean values was
      estimated at r = 0.82 (p < 0.0001). CONCLUSIONS: These observations suggest that
      to evaluate the intracranial compensatory reserve, the magnitude of 0.1 could be
      a useful threshold for the transfer function at the fundamental cardiac
      frequency.

PMID- 19388280
TI  - Cranioplasty effect on the cerebral hemodynamics and cardiac function.
AB  - BACKGROUND: Cranioplasty is usually performed for aesthetic, protective and
      patient comfort reasons. The objective of this study is to examine the effects of
      cranioplasty on the cerebral hemodynamics and cardiovascular system. METHODS:
      Twenty-seven patients who had undergone cranioplasty after extensive skull bone
      removal to prevent uncontrollable intracranial hypertension were included in this
      study. Arterial blood flow velocities in the middle cerebral artery (MCA) and
      internal carotid artery (ICA) were assessed by transcranial doppler (TCD). The
      cardiac functions were evaluated using the echocardiogram. And cerebral blood
      flow were measured by perfusion CT. FINDINGS: The blood flow velocity at the MCA
      ipsilateral to the cranioplasty was decreased from 50.5 +/- 15.4 cm/s
      preoperative to 38.1 +/- 13.9 cm/s following cranioplasty (p < 0.001) and from
      33.1 +/- 8.3 cm/s to 26.4 +/- 6.6 cm/s at the ICA (p < 0.001). The stroke volume
      was increased from 64.7 +/- 18.3 ml/beat, to 73.3 +/- 20.4 ml/beat (p < 0.001),
      while the cardiac output and mean arterial blood pressure were unchanged. The
      cerebral blood flow was increased from 39.1 +/- 7.2 ml/100g/min to 44.7 +/- 8.9
      ml/100g/min on the cranioplasty side (P = 0.05). CONCLUSIONS: Cranioplasty can
      get rid of the atmospheric pressure on the brain and increase the cerebral blood
      flow as well as improve the cardiovascular functions. A skull defect should be
      corrected, because cranioplasty has not only aesthetic or protective effects but
      also improves the cardiovascular functions.

PMID- 19388281
TI  - Hyperbaric oxygen therapy for consciousness disturbance following head injury in
      subacute phase.
AB  - BACKGROUND: Hyperbaric oxygen (HBO) therapy has been shown to improve outcome
      after brain injury, however its mechanisms are not understood. The purpose of the
      present study was to investigate the effect of hyperbaric oxygen (HBO) therapy on
      the cerebral circulation and metabolism of patients with disturbances in
      consciousness after head injury in the subacute phase. METHODS: Seven head injury
      patients underwent HBO treatment after leaving the intensive care unit. Oxygen
      (100% O2, 2.7 atm absolute) was delivered to patients in a hyperbaric chamber for
      60 min every 24 h (total five treatments/patient). Cerebral circulation
      monitoring (mean flow velocity: mFV, and pulsatility index: PI at horizontal
      portion of middle cerebral artery by transcranial Doppler) and cerebral
      metabolism monitoring (arterio-jugular venous difference of oxygen: AJDO2 and
      jugular venous lactate: lac-JV) before and after the series of treatments were
      evaluated. FINDINGS: Both PI and lac-JV were significantly decreased after HBO
      theatment, while there were no significant changes in mFV and AJDO2. The
      decreased PI and lac-JV after HBO therapy might indicate that this treatment
      couples cerebral circulation and metabolism. CONCLUSIONS: The measurement of
      cerebral circulation and metabolism parameters, especially PI and lac-JV, is
      useful for estimation of effect of HBO therapy in patients with distubances in
      consciousness after head injury in the subacute phase.

PMID- 19388282
TI  - Gender-related differences in intracranial hypertension and outcome after
      traumatic brain injury.
AB  - BACKGROUND: We have previously studied possible gender-related differences in
      intracranial hypertension and outcome following head injury. The results were
      always close to the limit of significance so that to achieve greater statistical
      power we have continued recruitment of patients for further 5 years. METHODS:
      Head injury patients (612) who were sedated and ventilated were studied from 1992
      2007. All had intracranial pressure (ICP), arterial blood pressure (ABP) and
      cerebral perfusion pressure (CPP) monitored continuously. Patients' outcome was
      assessed at 6 months post-injury (469 were available for follow-up). RESULTS:
      This retrospective analysis enrolled 98 females and 371 males. Males and females
      were well matched for age (mean +/- standard deviation: 33 +/- 17 and 33 +/- 16
      years respectively) and the initial median Glasgow Coma Score (GCS) [females and
      males 6]. The difference in mortality rate between sexes was age-related. In the
      subgroup of patients younger than 50 years mortality was 17% in males and 29% in
      females (p = 0.026), whereas there was no difference above 50 years (around 40%
      both males and females). Mean ICP, CPP and ABP were not different between males
      and females. However, cerebrovascular pressure reactivity was found to be
      significantly worse in females than in males in the age group below 50 years
      (PRx; males: 0.044 +/- 0.031; females 0.11 +/- 0.047; p < 0.05). CONCLUSION:
      Following head injury females younger than 50 have a significantly worse pressure
      reactivity and greater mortality rate than males of the same age.

PMID- 19388283
TI  - Long-term outcomes following decompressive craniectomy for severe head injury.
AB  - BACKGROUND: Severe head injury is one of the commonest indications for
      neurosurgical intervention. For the neurosurgeon, the operative last resort in
      cases of generalised brain oedema of traumatic origin is the decompressive
      craniectomy. Is it possible to use predictive factors to ascertain what degree of
      success, in terms of both the acute and long-term outcome, is to be expected in
      patients who undergo this treatment? METHODS: The clinical records of 131
      patients treated with decompressive craniectomy for severe head injury were
      evaluated. All patients were operated on between September 1997 and September
      2005 in the neurosurgical department of the Unfallkrankenhaus Berlin. A follow-up
      examination was carried out 49 +/- 25 months after the initial trauma. The
      clinical outcome was compared with several patient and radiographic factors to
      establish if any of these showed a relationship to the long-term outcome.
      FINDINGS: A significant relationship was demonstrated between quality of outcome
      and the Glasgow Coma Scale score on admission. Quality of outcome was similarly
      related to the age of the patient, the condition of the basal cisterns and the
      degree of midline shift in the initial cranial computed tomography. Factors which
      correlated with poor outcome included pupil reactivity on admission, established
      clotting disorders and posttraumatic hydrocephalus internus. Hyperglycaemia and
      initial acidosis were also associated with a poor outcome. CONCLUSIONS: The
      clinical outcome in patients with a severe head injury is to a great degree
      determined by the extent and type of the primary injury. When considering
      decompressive hemicraniectomy as a treatment for raised intracranial pressure
      following traumatic brain injury, the predictive factors detailed here should be
      taken into consideration.

PMID- 19388284
TI  - Relationship of a cerebral autoregulatory index with outcome in head injured
      patients.
AB  - BACKGROUND: Cerebral autoregulation is the process by which cerebral blood flow
      (CBF) is maintained constant over a specific cerebral perfusion pressure (CPP)
      range. We have reworked a version of the Ursino and Lodi autoregulation model to
      derive an index of autoregulation (G), and compared it to a number of other
      autoregulatory models as well as a gold standard measure of autoregulation
      obtained from an animal model study (6 piglets with a cranial window preparation
      and ICP, ABP sampled at 250 Hz). The results of that study have shown that this
      index G correlates well with the "Bouma" index of autoregulation. METHODS: In
      this study this new autoregulatory index has been calculated for a sample of 12
      head injury patient's data over multiple time points and then used to firstly
      investigate if this index in conjunction with other clinical prognostic factors
      may give a better indication of outcome and then analyse its trend with time to
      quantify how the level of autoregulation changes post-injury. FINDINGS: The index
      correlates well with dichotomised GOSe outcome (p = 0.03) and the trend in the
      result between middle and late time periods shows early signs of being predictive
      of outcome as well. CONCLUSIONS: Though more work is needed these results warrant
      further investigation with larger numbers of patients.

PMID- 19388285
TI  - Assessment of cerebrovascular resistance with model of cerebrovascular pressure
      transmission.
AB  - BACKGROUND: A two step modeling method of cerebrovascular pressure transmission,
      the dynamic relationship between arterial blood pressure (ABP) and intracranial
      pressure (ICP) has been developed as a means to continuously assess
      cerebrovascular regulation and resistance. Initially, system identification
      modeling was used to construct a numerical model of cerebrovascular pressure
      transmission. Next, the modal frequencies of the numerical model and the actual
      ABP recording were used to manipulate the parameters of a physiologically-based
      biomechanical model such that: (1) the actual and simulated ICP; and (2) the
      numerical and biomechanical model modal frequencies match. MATERIALS AND METHODS:
      This study was designed to compare changes of cerebrovascular resistance of the
      biomechanical model with the expected changes of cerebrovascular resistance
      associated with the occurrence of either a plateau wave or refractory
      intracranial hypertension. Pressure recordings from five patients with plateau
      waves and five patients with intracranial hypertension were used. FINDINGS:
      Vascular resistance decreased significantly during the plateau wave and was
      inversely related to CPP, indicating active vasoreactivity. In contrast, vascular
      resistance increased significantly during intractable intracranial hypertension
      and was directly related to CPP, indicating impaired cerebrovascular regulation.
      CONCLUSIONS: Such results support the use of the modeling method as a means to
      continuously assess changes of cerebrovascular regulation and resistance.

PMID- 19388286
TI  - Generation of very low frequency cerebral blood flow fluctuations in humans.
AB  - BACKGROUND: Slow oscillations of cerebral blood flow induced by synchronous
      variations of arterial blood pressure (ABP) are often used for clinical
      assessment of cerebral autoregulation. In the alternative scenario, spontaneous
      cerebral vasocycling may produce waves in cerebral blood flow that are, to a
      large extent, independent of ABP fluctuations. We use wavelet analysis to test
      the latter hypothesis. METHODS: The wavelet variability V(f), defined as the time
      averaged moduli of frequency dependent wavelet coefficients, is employed to
      analyze the relation between dynamics of arterial blood pressure and that of
      cerebral blood flow velocity in middle cerebral artery (MCA). FINDINGS: In the
      very low frequency (VLF, 0.02-0.07 Hz) band the variability in traumatic brain
      injury (TBI) patients with low intracranial pressure (V(ABP) = 0.36 +/- 0.28) is
      significantly smaller than that of the volunteers (V(ABP) = 0.70 +/- 0.25) with p
      = 7 x 10(-5). Interestingly, the corresponding variabilities of MCA flow velocity
      for both cohorts are comparable. V(MCA) = 0.83 +/- 0.65 of the brain injury
      patients is not statistically different from that of the volunteers V(MCA) = 1.06
      +/- 0.41 (p = 0.11). CONCLUSIONS: In TBI patients without cerebral hypertension,
      the VLF oscillations must have been spontaneously generated within intracranial
      volume to compensate for the reduced ABP variability. Vasomotion is identified as
      a plausible physiological mechanism underlying such oscillations. We argue that
      vasomotion may be beneficial for brain tissue oxygenation especially during
      periods of critically low perfusion.

PMID- 19388287
TI  - Accuracy of non-invasive ICP assessment can be increased by an initial individual
      calibration.
AB  - OBJECTIVE: In a formerly introduced mathematical model, intracranial pressure
      (ICP) could be non-invasively assessed using cerebral blood flow velocity (FV)
      and arterial blood pressure (ABP). The current study attempts to check whether
      the accuracy of the non-invasive ICP assessment (nICP) improves after an initial
      individual calibration by implanted ICP probes. METHODS: Thirteen patients with
      brain lesions (35-77 years, mean: 58 +/- 13 years) were studied. FV, ABP and ICP
      signals were recorded at days 1, 2, 4 and 7. nICP was calculated and compared to
      ICP. In the first recording of each patient the (invasively assessed) ICP signal
      was used to calibrate the nICP calculation procedure, while the follow-up
      recordings were used for its validation. FINDINGS: In 11 patients 22 follow-up
      recordings were performed. The mean deviation between ICP and the original nICP
      (+/- SD) was 8.3 +/- 7.9 mmHg. Using the calibrated method this deviation was
      reduced to 6.7 +/- 6.7 mmHg (P < 0.005). CONCLUSIONS: Initial individual
      calibration of nICP assessment method significantly improves the accuracy of nICP
      estimation on subsequent days. This hybrid method of ICP assessment may be used
      in intensive care units in patients with initially implanted ICP probes. After
      removal of the probes, ICP monitoring can be continued using the calibrated nICP
      assessment procedure.

PMID- 19388288
TI  - The impact of ventricular catheter impregnated with antimicrobial agents on
      infections in patients with ventricular catheter: interim report.
AB  - INTRODUCTION: Previous prospective study in our unit had shown that the use of
      dual antibiotic prophylaxis in patients with external ventricular drain was
      associated with decreased incidence of cerebrospinal fluid infection but
      complicated with opportunistic extracranial infection. In recent years,
      cerebrospinal fluid shunt catheters impregnated with antimicrobial agents have
      become available. Theoretically, these catheters provide antibiotic prophylaxis
      locally without the associated complications of systemic opportunistic infection.
      METHODS: We carried out a prospective randomized, controlled clinical trial in a
      regional neurosurgical center in Hong Kong. We recruited patients admitted for
      emergency neurosurgical operation after informed consent was obtained from next
      of-kin. Eligible patients were randomized to receive an antibiotic-impregnated
      ventricular catheter or plain ventricular catheter Dual prophylactic antibiotic
      coverage was given to the patients randomized for plain ventricular catheter
      only. Patients who received antibiotic impregnanted catheters were not treated
      with systematic prophylactic antibiotics. Here we present the analysis of 110
      patients, recruited over a 2-year period, to receive antibiotic-impregnanted
      ventricular catheters versus non-impregnated ventricular cathethers with
      prophylactic antibiotic coverage. FINDINGS: Fifty-two patients were randomized to
      antibiotic-impregnated ventricular catheter with no systemic antibiotic
      prophylaxis (Group A) and 58 patients were randomized to plain ventricular
      catheters with prophylactic dual antibiotics (Group B). There was no
      ventriculostomy-related infection in either groups of patients. There was also no
      statistical significant difference in incidences of extracranial infections
      between the two groups, p = 0.617. CONCLUSIONS: In this analysis, antibiotic
      impregnation of ventricular catheters was as effective as systemic antibiotics in
      the prevention of ventriculostomy infections, with the potential advantage of
      avoiding the systemic side-effects of prophylactic antibiotics.

PMID- 19388289
TI  - Assessment of mitochondrial impairment and cerebral blood flow in severe brain
      injured patients.
AB  - BACKGROUND: We believe that in traumatic brain injury (TBI), the reduction of N
      acetyl aspartate (NAA) occurs in the presence of adequate cerebral blood flow
      (CBF) which would lend support to the concept of mitochondrial impairment. The
      objective of this study was to test this hypothesis in severely injured patients
      (GCS 8 or less) by obtaining simultaneous measures of CBF and NAA. METHODS:
      Fourteen patients were studied of which six patients presented as diffuse injury
      at admission CT, while focal lesions were present in eight patients. CBF using
      stable xenon method was measured at the same time that NAA was measured by
      magnetic resonance proton spectroscopy (1HMRS) in the MR suite. Additionally,
      diffusion weighted imaging (DWI) and maps of the apparent diffusion coefficient
      (ADC) were assessed. FINDINGS: In diffuse injury, NAA/Cr reduction occurred
      uniformly throughout the brain where the values of CBF in all patients were well
      above ischemic threshold. In focal injury, we observed ischemic CBF values in the
      core of the lesions. However, in areas other than the core, CBF was above
      ischemic levels and NAA/Cr levels were decreased. CONCLUSIONS: Considering the
      direct link between energy metabolism and NAA synthesis in the mitochondria, this
      study showed that in the absence of an ischemic insult, reductions in NAA
      concentration reflects mitochondrial dysfunction.

PMID- 19388290
TI  - Mathematical models of cerebral hemodynamics for detection of vasospasm in major
      cerebral arteries.
AB  - BACKGROUND: Vasospasm is a common complication of aneurismal subarachnoid
      hemorrhage (SAH) that may lead to cerebral ischemia and death. The standard
      method for detection of vasospasm is conventional cerebral angiography, which is
      invasive and does not allow continuous monitoring of arterial radius. Monitoring
      of vasospasm is typically performed by measuring Cerebral Blood Flow Velocity
      (CBFV) in the major cerebral arteries and calculating the Lindegaard ratio. We
      describe an alternative approach to estimate intracranial arterial radius, which
      is based on modeling and state-estimation techniques. The objective is to obtain
      a better estimation than that offered by the Lindegaard ratio, that might allow
      for continuous monitoring and possibly vasospam prediction without the need for
      angiography. METHODS: We propose two new models of cerebral hemodynamics. Model 1
      is a more general version of Ursino's 1991 model that includes the effects of
      vasospasm, and Model 2 is a simplified version of Model 1. We use Model 1 to
      generate Intracranial Pressure (ICP) and CBFV signals for different vasospasm
      conditions, where CBFV is measured at the middle cerebral artery (MCA). Then we
      use Model 2 to estimate the arterial radii from these signals. FINDINGS:
      Simulations show that Model 2 is capable of providing good estimates for the
      radius of the MCA, allowing the detection of the vasospasm. These changes in
      arterial radius are being estimated from measurements of CBFV, and CBF is never
      being measured directly. This is the main advantage of the model-based approach
      where several interrelations between CBFV, ABP and ICP are taken into account by
      the differential equations of the model. CONCLUSIONS: Our results indicate that
      arterial radius may be estimated using measurements of ABP, ICP and CBFV,
      allowing the detection of vasospasm.

PMID- 19388291
TI  - Intracranial pressure in patients with sepsis.
AB  - INTRODUCTION: In sepsis the brain is frequently affected although there is no
      infection of the CNS (septic encephalopathy). One possible cause of septic
      encephalopathy is failure of the blood-brain barrier. Brain edema has been
      documented in animal models of sepsis. Aggressive fluid resuscitation in the
      early course of sepsis improves survival and is standard practice. We
      hypothesized that aggressive fluid administration will increase intracranial
      pressure (ICP) and may cause critical reductions in cerebral perfusion pressure
      (CPP). MATERIALS AND METHODS: Patients with sepsis were investigated daily on up
      to four consecutive days in the intensive care unit. Mean arterial blood pressure
      (MAP) and blood flow velocity in the middle cerebral artery were monitored for
      one hour each day. ICP was calculated non-invasively from MAP and flow velocity
      data. S-100beta was determined daily. FINDINGS: Fifty-two measurements were
      performed in 16 patients. ICP could be determined in 45 measurements in 15
      patients. Seven patients had an ICP > 15 mmHg and 11 patients had a CPP < 60 mmHg
      on at least 1 day. We found no significant correlation between ICP and fluid
      administration, but low CPP was significantly correlated with elevated S-100beta
      (r = -0.47, p = 0.001). CONCLUSIONS: Further research is needed to determine the
      role of ICP/CPP monitoring in patients with sepsis.

PMID- 19388292
TI  - Intracranial pressure and cerebral oxygenation changes after decompressive
      craniectomy in children with severe traumatic brain injury.
AB  - INTRODUCTION: There has been a resurgence of interest in decompressive
      craniectomy for traumatic brain injury (TBI), but the impact of craniectomy on
      intracranial pressure (ICP) and cerebral oxygenation has not been well described
      for diffuse injury in children. METHODS: ICP and brain tissue oxygenation (PbtO2)
      changes after decompressive craniectomy for diffuse brain swelling after TBI in
      children were analysed. FINDINGS: Decompressive craniectomy was performed for
      diffuse brain swelling in 18 children under 15 years old. For 8 patients,
      craniectomy was performed as an emergency for malignant brain swelling, and in
      10, for sustained ICP > 25 mmHg refractory to conventional medical treatment. In
      6 of these patients, PbtO2 was also monitored. Median ICP was reduced from 40
      mmHg before craniectomy to 16 mmHg for 24 hours thereafter, and PbtO2 improved
      from a median of 17.4 to 43.4 mmHg. Clinical outcome was favourable in 78%.
      CONCLUSIONS: In selected pediatric patients with TBI, craniectomy for diffuse
      brain swelling can significantly improve ICP and cerebral oxygenation control.
      The use of the procedure in appropriate settings does not appear to increase the
      proportion of disabled survivors.

PMID- 19388293
TI  - Are head injury guidelines changing the outcome of head injured children? A
      regional investigation.
AB  - BACKGROUND: Secondary pathophysiological CPP insult is related to outcome after
      head injury, and improved management would be expected to reduce secondary brain
      insult. Paediatric head injury management guidelines have been published in
      recent years, by SIGN (2000), RCPCH (2001), NICE (June 2003), and jointly by
      Critical/Intensive Care Societies (C/ICS July 2003). We investigated whether
      outcome of children's head injury (and total burden of secondary CPP insult) has
      changed (1) annually; (2) before and after the introduction of any HI guidelines,
      and (3) following other service changes. METHODS: Seventy-six children (aged 1-14
      years with severe HI) were admitted to the Edinburgh Regional Head Injury Service
      between 1989 and 2006, and dichotomised at various time points and compared in
      terms of: demographic factors, intracranial pressure (ICP), cerebral perfusion
      pressure (CPP) insults [e.g. age-banded pressure-time index (PTI)], and Glasgow
      Outcome Scale (GOS) score (assessed at 6 months post injury). FINDINGS: When
      dichotomised around the SIGN guidelines, there were no statistically significant
      differences between the two group's demography or in primary brain injury, but
      the outcomes were different (p = 0.03), with 6 vs 4 GOS1 (died), 2 vs 4 GOS3
      (severely disabled), 5 vs 16 GOS4 (moderately disabled) and 23 vs 14 GOS5 (good
      recovery), when comparing before and after year 2000. GOS4 was significantly
      different (chi-square = 7.99, p < 0.007). There was a (non-significant) trend for
      the later years to have longer insult durations of ICP, hypertension, CPP,
      hypoxia, pyrexia, tachycardia and bradycardia, greater PTI for both CPP and ICP,
      and more CPP insults (p = 0.003). There was, however, significantly less CPP
      insult (p = 0.030) after the introduction of the more management-oriented C/ICS
      guidelines. CONCLUSIONS: The most recent paediatric HI guidelines appear to have
      reduced the burden of secondary insult, but more time is required to determine if
      this will be reflected in improved outcomes.

PMID- 19388294
TI  - Low frequency pressure waves of possible autonomic origin in severely head
      injured children.
AB  - BACKGROUND: Useful information (both clinical and pathophysiological) which may
      be extracted from intracranial pressure (ICP) recordings include: (1) the mean
      level of ICP (and CPP), (2) cerebrovascular autoregulation status, (3) the
      intracranial pulse pressure (the pulse wave index, ICPpp/ICPm) or the pressure
      volume compensatory reserve index (RAP) and (4) the presence of any abnormal ICP
      waveform. This paper describes a slow frequency ICP waveform in children with TBI
      and postulates the pathophysiological basis and whether it contains clinically
      useful detail. METHODS: Children admitted to the Regional Head Injury Service in
      Edinburgh with TBI have continuously monitored ICP, MAP, CPP, and other
      physiological data (stored at a 1-min resolution). Slow frequency waveforms were
      noted, prompting a review of the stored monitoring from all cases over a 10 year
      period. FINDINGS: Episodic slow pressure waves were detected in 11 of 122
      severely head-injured (HI) children. The waveforms were detected in children of
      all ages (1.6-15 years) in the ICP signal, which were in phase with similar
      fluctuations in the MAP, CPP, and HR signals. Their mean periodicity was 1 per 7
      min (range 1 per 5-10 min), with a mean ICP pulse wave amplitude of 5.45 mmHg
      (range 4-7.5), and mean MAP pulse wave amplitude (pulse pressure) of 10.4 mmHg
      (range 4-15 mmHg). The duration was variable (range approx 2 h to 4.5 days). They
      were detected in the preterminal phase after serious HI, as well as in those
      children who made an independent recovery (GOS 4/5). The waves were not related
      to the mean levels of ICP, CPP, MAP, temperature or the state of cerebrovascular
      autoregulation. CONCLUSIONS: We postulate that these previously unreported slow
      waveforms may reflect the very low frequency (VLF) and ultra low frequency (ULF;
      < or = 1 per 5 min) components of heart rate and arterial blood pressure
      variability.

PMID- 19388295
TI  - Controlled lumbar drainage in medically refractory increased intracranial
      pressure. A safe and effective treatment.
AB  - BACKGROUND: A prospective study of lumbar CSF drainage in the setting of raised
      intra-cranial pressure refractory to medical management and ventriculostomy
      placement is presented. There have been no controlled trials of its use reported
      in the literature, to the best of our knowledge. METHOD: An IRB approved
      prospective study was conducted. 8 patients with increased intracranial pressure
      secondary to traumatic brain injury or aneurysm rupture were initially managed
      with sedation, ventriculostomy placement, mild hyperventilation (pCO2 = 30-35),
      and hyperosmolar therapy (Na = 150-155). A lumbar drain was placed if ICP
      continued to be above 20 mmHg despite optimization of medical therapy. FINDINGS:
      After lumbar drain placement, ICP was reduced from a mean of 27 +/- 7.8 to 9 +/-
      6.3, an average decrease of 18 mm H2O (p < 0.05). Requirements for hypertonic
      saline and/or mannitol boluses and sedation to control ICP were also decreased.
      There were no complications noted. CONCLUSIONS: We have shown that controlled
      lumbar drainage is a safe, efficacious and minimally invasive method for
      treatment of elevated ICP refractory to medical management. Ventriculostomies are
      always placed before utilizing lumbar drains to minimize the risk of cerebral
      herniation. We would advocate making controlled lumbar drainage a standard part
      of ICP control protocols.

PMID- 19388296
TI  - Decompressive craniotomy: durotomy instead of duroplasty to reduce prolonged ICP
      elevation.
AB  - BACKGROUND: Usually, decompressive craniectomy (DC) in patients with increased
      intracranial pressure (ICP) is combined with resection of the dura and large
      scale duroplasty. However, duroplasty is cumbersome, lengthens operation time and
      requires heterologous or autologous material. In addition, the swelling brain
      could herniate into the duroplasty with kinking of the superficial veins at the
      sharp cutting edges and subsequent ICP exacerbation. Several longitudinal
      durotomies avoid these limitations, but it remains a matter of discussion if
      durotomies reduce ICP sufficiently. METHODS: DC was performed in ten patients
      (mean age 45 years) with increased ICP after head trauma or subarachnoid
      hemorrhage. After craniectomy, the dura was opened by three to four durotomies
      from midline to the temporal base. Duration of surgical procedure and ICP during
      each surgical step and postoperatively were recorded. FINDINGS: Mean duration of
      surgery was 90 +/- 10 min. ICP prior to skin incision was 39 +/- 12 mmHg and
      dropped to 22 +/- 9 mmHg after craniectomy. During durotomy ICP decreased
      stepwise and reached stable values of 12 +/- 6 mmHg at the end of surgery. On
      days 1-10 after surgery, ICP values ranged between 12-17 mmHg. CONCLUSION: This
      study showed that durotomy is a fast and easy, but likewise effective method to
      lower ICP further after craniectomy.

PMID- 19388297
TI  - Ventriculostomy for control of raised ICP in acute traumatic brain injury.
AB  - The aim of this study was to evaluate the effect of ventriculostomy on
      intracranial pressure (ICP), and related parameters, including cerebrospinal
      compensation, cerebral oxygenation (PbtO2) and metabolism (microdialysis) in
      patients with traumatic brain injury (TBI). MATERIALS AND METHODS: Twenty-four
      patients with parenchymal ICP sensors were prospectively included in the study.
      Ventriculostomy was performed after failure to control ICP with initial measures.
      Monitoring parameters were digitally recorded before and after ventriculostomy
      and compared using appropriate tests. RESULTS: In all patients ventriculostomy
      led to rapid reduction in ICP. Pooled mean daily values of ICP remained < 20mmHg
      for 72h after ventriculostomy and were lower than before (p < 0.001). In 11 out
      of 24 patients during the initial 24-h period following ventriculostomy an
      increase in ICP to values exceeding 20mmHg was observed. In the remaining 13
      patients ICP remained stable, allowing reduction in the intensity of treatment.
      In this group ventriculostomy led to significant improvement in craniospinal
      compensation (RAP index), cerebral perfusion pressure and PbtO2. Improvement in
      lactate/pyruvate ratio, a marker of energy metabolism, was correlated with the
      increase in PbtO2. CONCLUSION: Ventriculostomy is a useful ICP-lowering
      manoeuvre, with sustained ICP reduction and related physiological improvements
      achieved in > 50% of patients.

PMID- 19388298
TI  - Intracranial pressure variability and long-term outcome following traumatic brain
      injury.
AB  - BACKGROUND: Research suggests that intracranial pressure (ICP) dynamics beyond
      just absolute ICP level provide information reflecting intracranial adaptive
      capacity. Specifically, evidence indicates that physiologic variability provides
      information about system functioning that may reflect dimensions of adaptive
      capacity. The purpose of this study was to examine the association between ICP
      variability in patients following moderate to severe traumatic brain injury (TBI)
      and outcome at hospital discharge and 6 months post-injury. METHODS: ICP was
      monitored continuously for 4 days in 147 patients (78% male; mean (SD) age = 37
      years (18 years)). ICP variability indices were calculated for four time scales
      (24 h, 60 min, 5 min and 5 s). Functional outcome was assessed using the Extended
      Glasgow Outcome Scale (GOSE). Logistic regression was used to estimate odds of
      survival or favorable outcome, and ordinal regression was used to estimate odds
      for outcome above versus below GOSE thresholds, predicted by ICP variability,
      controlling for age, gender, Glasgow Coma Scale motor score, craniectomy, and ICP
      level. FINDINGS: ICP variability indices were better predictors of 6-month
      outcome than mean ICP. Survival was significantly associated with greater 5-s ICP
      variability (p < 0.001). Higher ICP variability on shorter time scales was
      associated with better functional outcome (5-s RMSSD, 5-min SD: p < 0.002; 60-min
      SD: p < 0.011). CONCLUSIONS: ICP variability may reflect the degree of intactness
      of intracranial adaptive ability.

PMID- 19388299
TI  - Predictive values of age and the Glasgow Coma Scale in traumatic brain injury
      patients treated with decompressive craniectomy.
AB  - BACKGROUND: The use of decompressive craniectomy (DC) as an aggressive therapy
      for traumatic brain injury (TBI) has gained renewed interest. While age and the
      Glasgow Coma Scale (GCS) are frequently correlated with outcome in TBI, their
      prognostic values after decompressive craniectomy are ill-defined. METHODS: We
      retrospectively reviewed data from 103 TBI patients treated with DC from 2001 to
      2003. Age, preoperative GCS, and injury severity scores were recorded. Outcome at
      time of discharge was measured with the Glasgow Outcome Scale (GOS). Patients
      were stratified into the following age groups: < 35, 35-49, 50-64, and > or = 65
      years. Spearman's correlation coefficients between age, GCS, and GOS were
      calculated for the entire population and each age group. FINDINGS: Mortality
      rates for each age group were 19.2%, 66.7%, 60%, and 80%, respectively. There was
      a significant negative correlation between age and GOS (r = -0.42, p < 0.0001)
      and patients < 35 years had significantly better outcomes than patients > or = 35
      years (p < 0.0001). The overall correlation between GCS and GOS did not reach
      significance (r = 0.18,p = 0.076). When stratified by age, there was a
      significant correlation between GCS and GOS only in patients 35-49 years (r =
      0.51, p = 0.011). CONCLUSIONS: This data suggests that in TBI patients treated
      with DC, age correlates with outcome while the correlation between GCS and
      outcome is age-dependent.

PMID- 19388300
TI  - Noninvasive estimation of intracranial compliance in idiopathic NPH using MRI.
AB  - BACKGROUND: The pathophysiology of idiopathic normal pressure hydrocephalus (I
      NPH) is still unclear and the diagnosis is sometimes difficult. The aim of this
      study was to assess the biophysics of I-NPH by measuring intracranial compliance
      using cine MRI. METHODS: The study included patients with I-NPH (I-NPH group, n =
      13), brain atrophy or asymptomatic ventricular dilation (VD group, n = 10), and
      healthy volunteers (control group, n = 13). Net blood flow (bilateral internal
      carotid and vertebral arteries and jugular veins) and cerebrospinal fluid (CSF)
      flow in the subarachnoid space at the C2 cervical vertebral level were measured
      using phase-contrast cine MRI. CSF pressure gradient (PG(p-p)) and intracranial
      volume changes (VC(p-p)) during a cardiac cycle were calculated. FINDINGS: The
      compliance index (CI=VC(p-p)/PG(p-p)) in the I-NPH group was significantly lower
      than in the control and VD groups, whereas no difference was found between the
      control and VD groups. CI values of I-NPH patients after the tap test were larger
      than those before. These results clearly show that the intracranial compliance of
      I-NPH is relatively low compared to that of brain atrophy or normal subject. The
      increase of CI after a tap test also supports this finding. CONCLUSIONS: It is
      possible to estimate intracranial compliance as CI non-invasively using cine MRI.
      CI could become a useful method for the diagnosis of I-NPH.

PMID- 19388301
TI  - The role of cerebrospinal fluid flow study using phase contrast MR imaging in
      diagnosing idiopathic normal pressure hydrocephalus.
AB  - BACKGROUND: The purpose of this prospective study was to identify the ability of
      cerebrospinal fluid flow study using phase contrast MR imaging to replace the
      invasive methods currently used to establish the diagnosis of idiopathic normal
      pressure hydrocephalus (iNPH). MATERIALS AND METHODS: Between January 2003 and
      April 2005, 61 patients with clinical symptoms fitting the Hakim triad and a
      dilated ventricular system on CT underwent a intrathecal infusion test and
      cerebrospinal tap test. All patients also had a phase contrast MRI to determine
      the CSF flow rate in the aqueduct. Shunted patients were followed postoperatively
      up to 12 months. The pre- and postoperative symptomatic condition was evaluated
      using the clinical Kiefer score. The outcome was calculated by the NPH Recovery
      Rate. FINDINGS: Patients were classified into 41 with iNPH and 20 patients with
      brain atrophy. Thirty-nine iNPH patients were shunted and two patients refused
      surgery. The mean Kiefer score of the shunted patients was statistically
      significantly lower after surgery. In patients screened for clinical symptoms and
      ventriculomegaly on CT imaging, an aqueduct-CSF flow rate greater than 24.5
      ml/min was found to be statistically specific for a diagnosis of iNPH.
      CONCLUSIONS: The measurement of the CSF flow rate in the aqueduct by using the
      phase contrast MRI technique is a highly specific pre-selective method for
      diagnosing iNPH.

PMID- 19388302
TI  - Course of disease in patients with idiopathic normal pressure hydrocephalus
      (iNPH): a follow-up study 3, 4 and 5 years following shunt implantation.
AB  - BACKGROUND: In spite of recent advances in the diagnosis and treatment of iNPH,
      favorable outcomes following CSF diversion continue to be limited by
      complications, both valve dependent and valve independent, as well as by a
      reduction, over time, in the response to shunting. MATERIALS AND METHODS: Between
      September 1997 and December 2006, 148 patients underwent ventriculo-peritoneal
      shunt surgery in our department. All patients underwent the implantation of
      gravitational valves. These patients were followed-up 3, 6 and 12 months after
      surgery and then at annual intervals. FINDINGS: The mean age of the 94 men and 54
      women in our study was 68 years. The perioperative mortality was 0.7% (one
      patient died from a pulmonary embolism). A further 23 patients died during the
      follow-up period from causes unrelated to iNPH or the surgery. This study reports
      on groups of patients followed-up for 2 years (n = 92), 3 years (n = 62), 4 years
      (n = 38) and 5 years (n = 21) postoperatively. Valve independent complications
      occurred postoperatively in 6% of patients (n = 10). Of these, five patients (3%
      of the total) had an infection and catheter displacement was recorded in a
      further five. Valve dependent complications occurred in 24 patients (16%), with
      overdrainage found in seven patients (5%) and underdrainage apparent in 17 (11%).
      Responder rates were 79% at 2 years, 79% at 3 years, 64% at 4 years and 60% at 5
      years. The optimal valve opening pressure in programmable valves with a
      gravitational unit was between 30 and 70 mmHg. CONCLUSIONS: Sixty percent of
      patients with iNPH who underwent a ventriculo-peritoneal shunt using a
      gravitational valve continue to benefit from surgery 5 years postoperatively.

PMID- 19388303
TI  - Chronic hydrocephalus that requires shunting in aneurysmal subarachnoid
      haemorrhage [a-SAH]: its impact on clinical outcome.
AB  - BACKGROUND: Chronic hydrocephalus is a common occurrence following aneurismal
      subarachnoid haemorrhage [a-SAH] but its impact on neurological outcome has not
      been re reviewed systematically. PATIENTS AND METHODS: One hundred and eleven
      patients were recruited from a prospectively collected a-SAH registry over a 3
      year period between 2002 and 2004. Their 6-month extended Glasgow Outcome Scale
      [GOSE] scores were correlated with routine clinical data and the need for CSF
      shunting [chronic hydrocephalus that required shunting, CHS]. RESULTS: Thirty
      patients with CHS were identified and they were associated with an initial poor
      WFNS grading [median 4 versus 2, p = 0.028]. Among patients with poor WFNS
      grading, CHS was associated with a better GOSE [median 4 versus 2, p = 0.041] and
      among patients with good WFNS grading, CHS paradoxically was associated with a
      poor GOSE [median 3.5 versus 7, p = 0.016]. CONCLUSION: The relationships between
      CHS and GOSE in a-SAH were complex. Their true clinical significance requires a
      more in-depth prospective study.

PMID- 19388304
TI  - Morphological changes of intracranial pressure pulses are correlated with acute
      dilatation of ventricles.
AB  - BACKGROUND: Potentially useful information may exist in the morphological changes
      in intracranial pressure pulse therefore their extraction by automated methods is
      highly desirable. METHODS: Long-term continuous recordings of intracranial
      pressure and electrocardiogram (ECG) signals were analyzed for four patients
      undergoing intracranial pressure (ICP) monitoring with their implanted shunts
      externalized and clamped. A novel clustering algorithm was invented to process
      hours of continuous ICP recordings such that a dominant ICP pulse was extracted
      every 5 min. Morphological characteristics of dominant ICP pulses were then
      extracted after detecting characteristics points of a dominant ICP pulse that
      include the locations of ICP pulse onset, the first (P1), the second (P2), and
      the third peaks (P3) (or inflection points in the absence of peaks). FINDINGS: It
      was found that ratios of P2 amplitude to P1 amplitude and P3 amplitude to P1
      amplitude showed a strong increasing trend for a patient whose lateral ventricles
      were significantly enlarged (bi-frontal distance was 33 cm on day 0 and 37 cm on
      day 2) while there were no consistent trends in these morphological features of
      ICP pulse for the three patients whose ventricles size was not altered during the
      monitoring period. CONCLUSION: The present work demonstrates the usefulness of
      this novel ICP pulse analysis algorithm in terms of its potential capabilities of
      extracting predictive pulse morphological features from long-term continuous ICP
      recordings that correlate with the development of ventriculomegaly.

PMID- 19388305
TI  - Pulse amplitude of intracranial pressure waveform in hydrocephalus.
AB  - BACKGROUND: There is increasing interest in evaluation of the pulse amplitude of
      intracranial pressure (AMP) in explaining dynamic aspects of hydrocephalus. We
      reviewed a large number of ICP recordings in a group of hydrocephalic patients to
      assess utility of AMP. MATERIALS AND METHODS: From a database including
      approximately 2,100 cases of infusion studies (either lumbar or intraventricular)
      and overnight ICP monitoring in patients suffering from hydrocephalus of various
      types (both communicating and non-communicating), etiology and stage of
      management (non-shunted or shunted) pressure recordings were evaluated. For
      subgroup analysis we selected 60 patients with idiopathic NPH with full follow-up
      after shunting. In 29 patients we compared pulse amplitude during an infusion
      study performed before and after shunting with a properly functioning shunt.
      Amplitude was calculated from ICP waveforms using spectral analysis methodology.
      FINDINGS: A large amplitude was associated with good outcome after shunting
      (positive predictive value of clinical improvement for AMP above 2.5 mmHg was
      95%). However, low amplitude did not predict poor outcome (for AMP below 2.5 mmHg
      52% of patients improved). Correlations of AMP with ICP and Rcsf were positive
      and statistically significant (N = 131 with idiopathic NPH; R = 0.21 for
      correlation with mean ICP and 0.22 with Rcsf; p< 0.01). Correlation with the
      brain elastance coefficient (or PVI) was not significant. There was also no
      significant correlation between pulse amplitude and width of the ventricles. The
      pulse amplitude decreased (p < 0.005) after shunting. CONCLUSIONS: Interpretation
      of the ICP pulse waveform may be clinically useful in patients suffering from
      hydrocephalus. Elevated amplitude seems to be a positive predictor for clinical
      improvement after shunting. A properly functioning shunt reduces the pulse
      amplitude.

PMID- 19388306
TI  - The influence of co-morbidity on the postoperative outcomes of patients with
      idiopathic normal pressure hydrocephalus (iNPH).
AB  - BACKGROUND: A critical question in the diagnosis and treatment of idiopathic
      normal pressure hydrocephalus (iNPH) is that of which preoperative factors can
      most reliably predict outcomes following shunt insertion. The number and type of
      co-morbidities are increasingly being viewed as important predictive indicators.
      METHODS: Between 1997 and 2004, 95 patients were implanted with a gravitational
      ventriculo-peritoneal shunt as treatment for iNPH. All coincident disease
      processes were recorded. Eighty-two of these patients underwent follow-up 2 years
      postoperatively. The results of this prospective follow-up examination (Kiefer
      Score, NPH Recovery Rate) were compared with the preoperative CoMorbidity Index
      (CMI). FINDINGS: Of the patients with a CMI score of 0-1 (n = 18), 67%
      experienced an excellent outcome, 28% a good outcome and 5% and 0% a fair and
      poor outcome respectively. A CMI score of 2-3 was associated with markedly poorer
      outcomes (n = 33); 42% excellent, 30% good, 18% fair and 10% poor. A score of 4-5
      was related to 14% excellent, 27% good, 23% fair and 36% poor outcomes (n = 22).
      Remarkably few patients scoring between 6 and 8 on the CMI scale experienced a
      favourable outcome. The outcomes for this latter group were 0% excellent, 10%
      good, 45% fair and 45% poor (n = 9) significant predictor of the quality of
      clinical outcome for patients with iNPH undergoing shunt therapy.

PMID- 19388307
TI  - ICM+, a flexible platform for investigations of cerebrospinal dynamics in
      clinical practice.
AB  - BACKGROUND: ICM+ software encapsulates 20 years of our experience in brain
      monitoring gained in multiple neurosurgical and intensive care centres. It
      collects data from a variety of bedside monitors and produces on-line time trends
      of parameters defined using configurable signal processing formulas. The
      resulting data can be displayed in a variety of ways including time trends,
      histograms, cross histograms, correlations, etc. For technically minded
      researchers there is a plug-in mechanism facilitating registration of third party
      libraries of functions and analysis tools. METHODS: The latest version of the
      ICM+ software has been used in 162 severely head injured patients in the
      Neurosciences Critical Care Unit of the Addenbrooke's Cambridge University
      Hospital. Intracranial pressure (ICP) and invasive arterial blood pressure (ABP)
      were monitored routinely. Mean values of ICP, ABP, cerebral perfusion pressure
      (CPP) and various indices describing pressure reactivity (PRx), pressure-volume
      compensation (RAP) and vascular waveforms of ICP were calculated. Error-bar chart
      showing reactivity index PRx versus CPP ('Optimal CPP' chart) was calculated
      continuously. FINDINGS: PRx showed a significant relationship with CPP (ANOVA: p
      < 0.021) indicating loss of cerebral pressure-reactivity for low CPP (CPP < 55
      mmHg) and for high CPPs (CPP > 95 mmHg). Examining PRx-CPP curves in individual
      patients revealed that CPP(OPT) not only varied between subjects but tended to
      fluctuate as the patient's state changed during the stay in the ICU. Calculation
      window of 6-8 h provided enough data to capture the CPP(OPT) curve. CONCLUSIONS:
      ICM+ software proved to be useful both academically and clinically. The
      complexity of data analysis is hidden inside loadable profiles thus allowing
      clinically minded investigators to take full advantage of signal processing
      engine in their research into cerebral blood and fluid dynamics.

PMID- 19388308
TI  - Pathophysiology and diagnosis of spontaneous intracranial hypotension.
AB  - BACKGROUND: Spontaneous intracranial hypotension (SIH) has become a well
      recognized syndrome. However, diagnosis of SIH is still challenging. The problem
      with SIH is that the precise mechanism of cerebrospinal fluid (CSF) leakage
      remains largely unknown and there is no definite diagnostic criterion in the
      imaging. METHODS: The clinical findings of our ten cases and 301 literature
      reports on SIH were investigated in a retrospective analysis to clarify the
      pathophysiology of CSF leakage, correlate the findings of imaging studies and
      determine the most adequate diagnostic criteria. RESULTS: The events precede
      symptoms of SIH were categorized as traumatic, secondary and strictly spontaneous
      (62%). The location of the spinal CSF leak remains undetectable in approximately
      50% of cases reported. In 93% of patients, the CSF leakage sites were detected at
      the cervical or thoracic level of the spine. On recent MRI studies, 88% of
      patients showed spinal epidural fluid collections that most likely represent CSF
      leakage. MR myelography using heavily T2-weighted fast-spin-echo sequence can
      clearly demonstrate the site of CSF leakage. Although numerous treatment options
      are available, none of the treatments have been evaluated by randomized clinical
      trials. In 48% of papers, autologous epidural blood patch (EBP) was the treatment
      of choice in patients who have failed initial conservative management. Forty-nine
      percent of patients showed relief of symptoms after up to three repeated EBPs.
      CONCLUSION: We propose new diagnostic criteria of SIH to avoid misdiagnosis.

PMID- 19388309
TI  - Intraoperative infrared brain surface blood flow monitoring during superficial
      temporal artery-middle cerebral artery anastomosis in a patient with moyamoya
      disease: clinical implication of the gradation value in postoperative clinical
      course--a case report.
AB  - BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA)
      anastomosis is a safe and effective treatment for moyamoya disease. Symptomatic
      cerebral hyperperfusion is a potential complication of this procedure, especially
      in adult cases. Accurate diagnosis of postoperative hyperperfusion is important
      because its treatment is contradictory to that for ischemia. Intraoperative
      techniques to detect hyperperfusion are still lacking. METHODS: We performed
      intraoperative infrared (IR) brain surface monitoring in a 36-year-old man who
      underwent left STA-MCA anastomosis. FINDINGS: IR monitoring not only detected the
      patency of bypass, as also confirmed by conventional Doppler sonography and
      postoperative magnetic resonance angiography, but also delineated the local brain
      surface hemodynamics after revascularization. Analysis of gradation value
      disclosed an abnormal increase in brain surface cerebral blood flow (indirectly
      indicated as a temperature change) after removal of the temporary clip. The
      patient suffered from transient right upper extremity numbness and dysarthria due
      to focal hyperperfusion from postoperative days 2 through 6. Intensive blood
      pressure control completely relieved his symptoms, and he was discharged without
      neurologic deficit. CONCLUSIONS: Intraoperative brain surface monitoring by IR
      imaging may be useful to predict cerebral hyperperfusion after revascularization
      surgery for moyamoya disease. Further evaluation with a larger number of patients
      is necessary to validate this technique.

PMID- 19388310
TI  - Clinical study of craniospinal compliance non-invasive monitoring method.
AB  - BACKGROUND: The ability to quantify non-invasively the effect of posture on
      intracranial physiology by using cine phase-contrast MRI may lead to the
      development of new diagnostic tests to evaluate such functions as regulation of
      CBF and ICP, and the effect of pathologies on these functions. METHODS: Results
      similar to MRI technology can be obtained using non-invasive ultrasonic method
      (Vittamed) for intracranial blood volume pulse wave (IBVPW) measurement and
      intracraniospinal compliance (ICC) monitoring. FINDINGS: IBVPW have been
      investigated in supine and upright positions of healthy volunteers using Vittamed
      technology. A group of 13 healthy volunteers (nine females, four males, mean age
      25.1 +/- 3.4) was studied. More than 3,000 IBVPW were analysed in order to show
      the difference of shape and amplitude in supine and upright positions. Averaged
      shape of ten IBVPW waves was presented in the normalized window with dimensions
      1.0 x 1.0. CONCLUSIONS: The results show significant difference between averaged
      IBVPW shapes in upright (highest intracraniospinal compliance) and supine (lower
      intracraniospinal compliance) body positions. Body posture caused IBVPW subwave
      P2 and P3 changes deltaP2 = 18% and deltaP3 = 11%. Amplitude of IBVPW in upright
      body position was significantly higher than in the supine one. The value of IBVPW
      amplitude's ratio in supine and upright positions was 1.55 +/- 0.61.

PMID- 19388311
TI  - Cerebral CO2 reactivity in severe head injury. A transcranial Doppler study.
AB  - BACKGROUND: Cerebral circulation is profoundly affected by changes in PaCO2. CO2
      manipulation plays a basic role in the management of intracranial hypertension;
      CO2 reactivity (CO2R) defines the changes in CBF in response to changes in PaCO2.
      Transcranial Doppler has allowed exploring its effects "on line". MATERIALS AND
      METHODS: We conducted a prospective clinical trial, with the objective of
      studying CO2R in severe head injury patients. Sixteen severe traumatic brain
      injury patients, mechanically ventilated, were included. Monitoring of MAP, ICP,
      CPP, SjO2, ETCO2, and cerebral blood flow velocity (CBFV) was performed. Taking
      into account basal cerebral hemodynamic pattern, minute ventilation was modified
      to attain a negative ("A") or positive ("B") deltaPCO2. CO2R was calculated as:
      CO2R = % deltaCBFV/deltaETCO2 in mmHg (normal value 3.7 +/- 1%/mmHg). CO2R was
      compared with deltaICP/ deltaPCO2 in each patient. FINDINGS: Three patients were
      excluded because the change in ETCO2 was too low (deltaETCO2 < 3 mmHg). The
      median value of CO2R in the total group of 13 patients was 3.38. In "A" the
      values tended to be lower than in "B". There were four low CO2R values in "A" and
      none in "B". There was no significant correlation between CO2R and
      deltaICP/deltaPCO2. CONCLUSIONS: The different "A" and "B" behavior might be due
      to dissimilar mechanisms involved in the basis of vasodilatation and
      vasoconstriction. Changes in ventilation must be performed with caution, avoiding
      sudden increases in CO2 that may increase ICP. The absence of correlation between
      CO2R and deltaICP/deltaPCO2 is explained, at least partially, by different cranio
      cerebral compliance in each patient. Therefore, induced blood volume changes are
      not directly transmitted to ICP, but their effects depend on the shape of the
      pressure-volume curve and the position on the curve in which each situation is
      working.

PMID- 19388312
TI  - Acetazolamide vasoreactivity evaluated by transcranial power harmonic imaging and
      Doppler sonography.
AB  - BACKGROUND: Cerebral vasoreactivity (CVR) in the major cerebral arteries
      evaluated by transcranial Doppler sonography has shown some correlation with CVR
      in the brain tissue measured by other neuroradiological modalities. To clarify
      vasoreactive differences in the brain tissue and the major cerebral arteries, we
      have evaluated the relationship of acetazolamide (ACZ) CVR between transcranial
      ultrasonic power harmonic imaging (PHI) and color Doppler sonography (CDS), in
      cases ofparenchymal pathology with and without occlusive vascular lesions.
      MATERIALS AND METHODS: The subjects were 31 stroke patients with intraparenchymal
      pathologies, 15 with (occlusive group) and 16 without (non-occlusive group)
      occlusive carotid and/or middle cerebral artery lesions. CVR based on values
      before/after ACZ (angle-collected CDS velocity in the middle and posterior
      cerebral arteries, PHI contrast area size, peak intensity, time to peak
      intensity), and correlation of CVR between PHI and CDS were compared between the
      side with and without lesions in both groups. FINDINGS: (a) PHI CVR tended to be
      more disturbed than CDS CVR. CVR side differences were not significant. (b) CVR
      correlations between PHI and CDS were always lower in the pathological sides.
      CONCLUSIONS: CVR in brain tissue evaluated by PHI is susceptible to disturbance
      in comparison with CDS, due to both parenchymal and vascular occlusive
      pathologies.

PMID- 19388313
TI  - A new semi-invasive method for two dimensional pO2 measurements of cortical
      structures.
AB  - BACKGROUND: Measuring brain oxygenation in patients with TBI or SAH is of major
      interest. We present a new semi-invasive method for two dimensional measurements
      of cortical pO2. METHODS: For this feasibility study, a porphyrin containing
      sensor foil was placed directly on the cortex of intubated and variably
      ventilated Wistar rats. The sensor was excited with a light pulse and pictures of
      the foil's pO2 dependant emissions were captured with a CCD camera. After online
      data processing, two-dimensional maps of cortex oxygenation were displayed and
      analyzed using ROIs (here: arteriole, vein, parenchyma) with a display rate of 7
      Hz. The size of one single measurement pixel was 0.03 x 0.03 mm2. FINDINGS: The
      mean pO2 over cortex arterioles was 20.3 +/- 0.69, over veins 17.1 +/- 0.5 and
      over parenchyma 9.1 +/- 0.6 (mmHg +/- SD). The arterial pO2 showed a good
      correlation to the pO2 in the ROIs (r = 0.46-0.72, p < 0.0001, n = 198).
      Comparing groups with different paO2 and paCO2 we found significantly different
      pO2 values in the ROIs of the cortex. CONCLUSIONS: This prototype is capable of
      obtaining cortical pO2 maps with excellent temporal and spatial resolution and
      provides simultaneous imaging of the cortex structures.

PMID- 19388314
TI  - The relationship between intracranial pressure and brain oxygenation following
      traumatic brain injury in sheep.
AB  - BACKGROUND: While it is understood that raised intracranial pressure (ICP) after
      traumatic brain injury (TBI) may negatively impact on brain tissue oxygenation
      (PbtO2), few studies have characterized the inter-relationship between these two
      variables, particularly in a large animal model that replicates the human
      gyrencephalic brain. The current study uses an ovine model to examine the
      dynamics of ICP and PbtO2 after TBI. MATERIALS AND METHODS: Five 2-year-old male
      Merino sheep were anesthetized with isoflurane and impacted in the left temporal
      region using a humane stunner. ICP and PbtO2 were then monitored over the
      following 4 h using a Codman ICP Express monitoring system and a LICOX brain
      tissue oxygen monitoring system, respectively. Two additional sheep were
      anesthetized and monitored as sham (uninjured) controls. FINDINGS: Mean ICP 60
      min following TBI was over 25 mmHg (p < 0.05 versus controls) and by 4 h, values
      were consistently greater than 30 mmHg (p < 0.001). With respect to PbtO2, values
      fell from mean control values of 52 +/- 11 to 20 +/- 4 mmHg by 60 min (p < 0.001)
      and by 4 h to 14 +/- 3 mmHg (p < 0.01). The sigmoidal relationship between the
      two variables included a negative linear correlation when ICP was between 13 to
      27 mmHg. CONCLUSIONS: Our results suggest that TBI results in early changes in
      ICP that are associated with profound declines in PbtO2, and may indicate the
      need for earlier management of ICP after TBI.

PMID- 19388315
TI  - Dual microdialysis probe monitoring for patients with traumatic brain injury.
AB  - BACKGROUND: In vivo microdialysis can be used to examine the focal metabolism by
      measuring the extracellular concentration of amino acids and other biochemicals
      in the focal brain tissue in which the probe is placed. We report two patients
      with traumatic brain injury who underwent placement of dual microdialysis probes.
      MATERIALS AND METHODS: One probe was placed in the penumbra zone and another in a
      region remote to the injury. Multiple measurements of several biochemical's were
      made. FINDINGS: In the first case, a 54-year-old man with right acute subdural
      hematoma and right fronto-temporal contusion was monitored. Quantitative analysis
      of in vivo microdialysis was performed. While the extracellular concentration of
      lactate and glycerol were higher in the penumbra zone than in the region remote
      to the injury, glutamate remained lower in the penumbra zone than in the remote
      region. In the second case, dual microdialysis probes were placed in a 56-year
      old woman with left acute subdural hematoma and left fronto-temporal lobe
      contusion. Also in this case, the extracellular glutamate remained lower in the
      penumbra zone than in the remote region. CONCLUSIONS: The reason why the
      extracellular glutamate value remained lower in the penumbra zone than in the
      remote region is unclear. The position of each microdialysis probe was ensured by
      CT scan after the operation. It is important to be aware of the limitations of
      performing microdialysis in brain injured patients with a single probe.

PMID- 19388316
TI  - In vitro comparison of two generations of Licox and Neurotrend catheters.
AB  - BACKGROUND: Clinical reports on brain tissue oxygen tension differ in suggested
      threshold values for defining cerebral ischemia using the Licox and
      Neurotrend/Paratrend system. We evaluated in vitro performance of both first and
      second generation devices. MATERIALS AND METHODS: Response rate and accuracy in
      solutions with oxygen tensions from 0 to 150 mm Hg were measured. FINDINGS:
      Ninety-five percent Response times were 102 +/- 13 seconds for first generation
      Licox probes and 135 +/- 24 s for Paratrend (n = 6, each probe), with second
      generation probes at 134 +/- 4 and 116 +/- 16 s respectively. At pO2 150 mmHg
      Licox and Paratrend probes were accurate with 2.2% and 2.1% error, respectively
      and 2.6% and 4.1% for later generation. At pO2 18 mmHg, Paratrend overestimated
      by 16.5% (absolute error range 2.18 to 4.18 mmHg), 7.4% for Neurotrend, Licox
      underestimated by 1.8% (absolute error range 0.08 to 0.52 mmHg) with 3.6% for the
      second generation probe. CONCLUSIONS: Differences between the first generation
      probe types, while statistically significant (p < 0.001), may not be clinically
      relevant. Overestimation of pO2 by Neurotrend and small underestimation by Licox
      partially explain differences in published thresholds for cerebral ischemia. The
      Neurotrend was slightly more accurate and faster than the Paratrend system.

PMID- 19388317
TI  - Cerebral metabolism monitoring during hypothermia following resuscitation from
      cardiopulmonary arrest.
AB  - BACKGROUND: The aim of the present study was to evaluate cerebral metabolism
      monitoring during therapeutic hypothermia for global ischemic brain damage after
      cardiopulmonary resuscitation (CPR). METHODS: Jugular venous sampling and
      positron emission tomography (PET) were used. Seven comatose patients with
      cardiopulmonary arrest underwent hypothermia treatment as soon as possible after
      CPR. The body temperature of these patients was maintained at 34 degrees C for 72
      h. Rewarming was performed at a rate of 1 degrees C/day. To monitor jugular
      venous saturation (SjO2) and lactate (lac-JV), a fiberoptic catheter was inserted
      into the jugular bulb. Oxygen extraction fraction (OEF) was calculated using the
      difference between arterial oxygen saturation (SaO2) and SjO2. 18F
      fluorodeoxyglucose (FDG) PET was performed to investigate cerebral glucose
      metabolism at the end of therapeutic hypothermia. FINDINGS: The OEF was
      significantly increased at the end of hypothermia in four patients with favorable
      outcome on the Glasgow Outcome Scale (hypothermia onset 15.3 +/- 2.0% vs.
      hypothermia end 30.3 +/- 2.8%, P < 0.05). In three patients with unfavourable
      outcome (severe or worse on the Glasgow Outcome Scale), end hypothermia OEF
      tended to be low. There was also a reduction in FDG uptake in these three
      patients with unfavourable outcome. The lac-JV was significantly decreased at the
      end ofhypothermia treatment compared with hypothermia onset (27.7 +/- 7.4 vs. 6.0
      +/- 3.0 mg/dL, P < 0.05). CONCLUSIONS: The measurement of cerebral metabolism
      parameters, especially OEF, might be useful for estimation of hypothermia therapy
      in patients with unconsciousness after resuscitation after cardiac arrest.

PMID- 19388318
TI  - Nitric oxide in acute brain injury: a pilot study of NO(x) concentrations in
      human brain microdialysates and their relationship with energy metabolism.
AB  - INTRODUCTION: This pilot microdialysis study in acute brain injury patients
      assessed the relationship between nitric oxide products (total nitrite plus
      nitrate, termed NO(x)) and energy-related molecules: glucose, lactate, pyruvate,
      glutamate and glycerol. METHODS: Twelve patients (11 major head-injury and one
      subarachnoid haemorrhage) were studied, 11 of which had single catheters and one
      had two catheters, in the cerebral cortex. Catheters were perfused at 0.3
      microL/min with CNS perfusion fluid. Collection vials were changed hourly.
      Microdialysates were analysed for energy-related molecules on a CMA600 or ISCUS
      analyser, and for NO(x) using a purge vessel (VCl3 plus HCl at 95 degrees C,
      purged with nitrogen) connected to a Sievers NOA 280i analyser. FINDINGS: The
      mean of mean NO(x) concentration (+/- SD) for the 13 catheters was 32.7 +/- 16.8
      micromol/L, and the lactate/ pyruvate ratio was 38.6 +/- 20.1. Increasing NO(x)
      concentrations correlated significantly with decreasing lactate/ pyruvate ratio
      (Spearman r = -0.79, p = 0.0065), with decreasing lactate concentration (r = 
      0.59, p = 0.042), and with increasing glucose concentration (r = 0.71, p =
      0.018). CONCLUSIONS: These pilot data suggest that in injured brains, higher
      concentrations of nitric oxide are associated with more favourable metabolism.
      Nitric oxide may act beneficially by increasing blood flow and delivery of oxygen
      and glucose. Further patients are being recruited.

PMID- 19388319
TI  - The brain monitoring with Information Technology (BrainIT) collaborative network:
      data validation results.
AB  - BACKGROUND: The BrainIT group works collaboratively on developing standards for
      collection and analyses of data from brain injured patients towards providing a
      more efficient infrastructure for assessing new health technology. MATERIALS AND
      METHODS: Over a 2 year period, core dataset data (grouped by nine categories)
      were collected from 200 head-injured patients by local nursing staff. Data were
      uploaded by the BrainIT web and random samples of received data were selected
      automatically by computer for validation by data validation (DV) research nurse
      staff against gold standard sources held in the local centre. Validated data was
      compared with original data sent and percentage error rates calculated by data
      category. FINDINGS: Comparisons, 19,461, were made in proportion to the size of
      the data received with the largest number checked in laboratory data (5,667) and
      the least in the surgery data (567). Error rates were generally less than or
      equal to 6%, the exception being the surgery data class where an unacceptably
      high error rate of 34% was found. CONCLUSIONS: The BrainIT core dataset (with the
      exception of the surgery classification) is feasible and accurate to collect. The
      surgery classification needs to be revised.

PMID- 19388320
TI  - BrainIT collaborative network: analyses from a high time-resolution dataset of
      head injured patients.
AB  - BACKGROUND: The BrainIT project was conceived in 1997 and has grown into an
      international collaboration with the purpose of gathering high time resolution
      data from head injured patients utilising standardised methodologies. MATERIALS
      AND METHODS: From 1998, 22 participating neuroscience centres collected three
      main types of information: demographic, physiological data and clinical treatment
      information. A data collection solution was provided for each centre dependent on
      their existing facilities and data were collected for the duration of monitoring
      as defined by the routine care in each centre. On completion of ICP monitoring
      all personal information was removed and then transferred to Glasgow via the
      internet where it was converted into a standard format and entered into a central
      database. Outcome was measured using the extended Glasgow Outcome Score using an
      interview questionnaire. FINDINGS: Data has been obtained from a total of 349
      patients (277 male and 72 female) The age of these patients ranged from 1 to 87
      years (median 31); 145 had been involved in a traffic accident and 32 were
      pedestrians; 78 had suffered a fall; 24 were assaulted and the remaining 70 of
      other causes. A large amount of physiological data was collected (e.g. BP 2,531
      days, ICP 2,212 days in total). This dataset has provided the opportunity to
      perform unique analysis and these include the statistical features of blood
      pressure, diurnal variations in ICP, optimal sampling rate determination and a
      comparison of summary measures of secondary insults. CONCLUSIONS: This
      challenging collaboration has brought together a large number of centres and
      developed a successful clinical research network focussed on improving the
      treatment of head injured patients. It has successfully collected a vast quantity
      of high quality data that provides a rich source for analysis and hypothesis
      testing.

PMID- 19388321
TI  - Pilot application of fractal characterisation and its response to change on
      physiological wave forms.
AB  - BACKGROUND: Over the last two decades the advances in analysis techniques for
      physiological time series data have been moving from the classical statistics to
      a more nonlinear or chaos based approach to looking at patterns in the
      variability of the time series. From this work it can be shown that physiological
      time series exhibit complex multi-fractal properties. So by designing a
      classification based on this nonlinear and chaotic nature you can detect changes
      and alterations in the underlying physiological processes. METHODS: Applying a
      proven relationship between the wavelet modulus maxima representation and the
      Holder exponent we could assess the multi fractal nature of the of the signal
      detection underlying changes in the physiology. Using two distinct techniques one
      global and the other localised in time, classification of two distinct the time
      series was carried out firstly via the analysis of the distribution of the Holder
      exponents over all scales of the signal and secondly via a moving window
      application of the mean Holder function. FINDINGS: The distribution methodology
      did not return significant results though this is probably more to do with the
      signal than the technique. The trending approach shows a predictive nature with
      slope being linked to increased instability in the signal content. CONCLUSIONS:
      Overall this study has shown the applicability of the techniques which definitely
      warrant further refinement and study.

PMID- 19388322
TI  - The predictive value of ICP as compared to magnetic resonance imaging in comatose
      patients after head injury.
AB  - INTRODUCTION: While highly increased intracranial pressure (ICP) is of high
      predictive value indicating a fatal outcome, the predictive value of moderately
      increased ICP early after head injury remains uncertain. We compared the
      predictive value of ICP to the predictive value of magnetic resonance imaging
      (MRI) early after head injury. METHODS: 55 patients with a Glasgow Coma Scale
      (GCS) of less than 8, for more than 24 hours after head injury were investigated.
      Outcome was classified according to the Glasgow Outcome Scale (GOS). All patients
      received registration of ICP upon arrival at the hospital and an initial cranial
      computerized tomography scan. An MRI study was subsequently performed within 10
      days of admission. The highest mean ICP registered within one hour in the first
      day of admission and the location of lesions as identified by MRI were related
      with outcome. RESULTS: ICP was neither related with mortality nor with GOS of
      survivors. The location of lesions as depicted by MRI proved to be statistically
      significantly related with the GOS (p < 0.001). Age proved to be clearly and
      significantly related with outcome (p = 0.019). CONCLUSIONS: Our current MRI
      findings suggest that the location of the initial brain injury lesion correlates
      with outcome at 6 months. No such correlation could be identified for
      intracranial pressure on the first day after head injury (p = 0.766).

PMID- 19388323
TI  - Metabolic disturbance without brain ischemia in traumatic brain injury: a
      positron emission tomography study.
AB  - BACKGROUND: Cerebral ischemia is believed to be an important mechanism of
      secondary neuronal injury in traumatic brain injury (TBI). METHODS: In this
      study, we performed 15O2 positron emission tomography (PET) studies to measure
      the cerebral blood flow (CBF) and oxygen metabolism (CMRO2) in the
      pericontusional region in a total of 15 patients (11 males, 4 females, aged 15-81
      years) who sustained TBI with contusional hematoma. PET studies were performed a
      mean of 13.5 +/- 9.1 days (range 2-33 days) after TBI occurred. FINDINGS: The
      areas of pericontusional tissues located 10 mm away from the cerebral contusion
      exhibited mildly decreased CBF (89%) and severely suppressed CMRO2 (67%) when
      comparison was made with the remote cerebral cortex. Severely suppressed oxygen
      metabolism in the pericontusional tissue was observed not only in the acute
      stage, but also in the subacute stage after TBI, whereas blood flow was slightly
      recovered in the subacute stage. We also compared the PET findings obtained in
      the acute or subacute stage after TBI and structural abnormalities on late-stage
      MRI in 5 patients. The area of flow defect on the CBF-PET image developed into
      irreversible tissue damage (necrosis) in the chronic stage. The area of
      hypoperfusion surrounding the lesion partly resulted in tissue necrosis: however,
      a large part of the hypoperfused tissue survived in the chronic stage. Again, a
      significant portion of oxygen hypometabolism surrounding the lesion did not
      develop into tissue necrosis. CONCLUSIONS: We conclude that impaired cerebral
      blood flow and metabolism in the pericontusional region is observed even in the
      subacute stage after TBI and is unlikely to cause severe further neuronal damage.

PMID- 19388324
TI  - Concordant biology underlies discordant imaging findings: diffusivity behaves
      differently in grey and white matter post acute neurotrauma.
AB  - BACKGROUND: Cerebral edema is a common sequelum post traumatic brain injury
      (TBI). Quantification of the apparent diffusion coefficient (ADC) using diffusion
      tensor imaging (DTI) may help to characterize the pathophysiology of brain
      swelling. METHODS: Twenty-two patients with moderate-to-severe TBI underwent
      magnetic resonance (MR) imaging, including DTI, within five days of injury. The
      mean ADCs in whole brain white matter, whole brain grey matter and entire brain
      were calculated and compared to twenty-five controls. FINDINGS: A significant
      decrease in the grey matter ADC (p < 0.001), significant increase in the white
      matter ADC (p < 0.001) and no significant change in the whole brain ADC (p =
      0.771) was observed. No significant correlation was found between DTI parameters
      in any of the three regions of interest (ROI) and GCS, time to scan, intracranial
      pressure (ICP) before and during the time of the scan, cerebral perfusion
      pressure at time of scan, or Glasgow Outcome Score (GCS). CONCLUSIONS: The
      decrease in ADC seen in the grey matter is consistent with cytotoxic edema. The
      increase in ADC in the white matter indicates damage that has led to an overall
      less restricted diffusion. This study assists in the interpretation of the ADC by
      showing that the acute changes are different in the whole brain white and grey
      matter ROIs post TBI.

PMID- 19388325
TI  - Qualitative aspects of cranial CT perfusion scanning in a mixed neurosurgical
      patient collective.
AB  - BACKGROUND: In patients with ischemic stroke, computer tomography (CT) perfusion
      imaging provides rapid information on the penumbra adjacent to the infarct core.
      For neurosurgical patients with acute brain injury, the value of CT perfusion is
      undecided up to now. We present our experience in a series of 78 examinations in
      35 patients with acute intracranial pathology. METHODS: CT perfusion was
      performed with a Siemens Emotion Duo CT scanner using a single slice at the level
      of the upper basal ganglia. Color maps of time to peak (TTP), cerebral blood flow
      (CBF) and cerebral blood volume (CBV) were analyzed according to qualitative
      criteria. Quantitative evaluation with self-defined regions of interest was not
      performed due to repeatability problems and inconsistent data. FINDINGS: TTP
      showed an interhemispheric difference in 45% and regional prolongation in 16% of
      the scans. Global TTP was prolonged in 60%, while global CBF was reduced in 43%.
      Two patients showed hyperemia. A CBF/CBV mismatch, indicating non-infarcted
      penumbra at risk, was seen in 67%. Six patients with aneurysmal SAH showed
      reduced CBF, and consecutive angiography confirmed vasospasm in every case.
      CONCLUSIONS: CT perfusion scanning gives valuable information at a low risk and
      with negligible additional time after a routine cranial CT. In our opinion, this
      modality may have considerable impact on the clinical management of severely
      brain injured patients in future.

PMID- 19388326
TI  - Study of perfusion in and around cerebral contusions by means of computed
      tomography.
AB  - BACKGROUND: Several authors have found low absolute values of cerebral blood flow
      (CBF) in both contusion core and pericontusional parenchyma ofhead-injured
      patients by means of Xenon Computed Tomography (CT). Perfusion CT has become
      available as a new and validated tool for studying CBF in patients. The aim of
      the present study was to assess the relation between volume expansion of
      contusions and pericontusional CBF measured by perfusion CT. METHODS: Eight head
      injured patients with a contusion on the admission CT head scan underwent a
      perfusion CT scan within 48 hours post trauma. The patients received standard
      head injury management. The eventual maximum contusion volume was assessed on the
      follow up plain CT scans. FINDINGS: Expansion of the contusion was observed in 6
      patients. Reduced CBF was found in all contusions with absolute CBF values below
      10 ml/100 g/min in the CT hyperdense/mixed density areas and below 20 ml/100
      g/min in the surrounding hypodense areas. Penumbra areas, when defined by a mean
      transit time > 150% and cerebral blood volume > 2 ml/100 g, were limited to thin
      concentric rims surrounding the ischemic cores. We could not find a pattern of
      CBF that predicted contusion expansion. CONCLUSIONS: Based on the present
      preliminary data there is no indication that contusion expansion can be predicted
      on the basis of pericontusional CBF data.

PMID- 19388327
TI  - Magnetic resonance measurement of blood and CSF flow rates with phase contrast-
      normal values, repeatability and CO2 reactivity.
AB  - BACKGROUND: Similarity in flow pulsatility has been proposed as a basis for semi
      automated segmentation of vessel lumens for MR-based flow measurement, but re
      examinations of salient aspects of the methodology have not been widely reported.
      METHODS: 12 normal control subjects underwent repeated (3*Baseline+1*5%CO2) phase
      contrast measurements of CSF flow through the cerebral aqueduct and foramen
      magnum, and CBF through the 6 large cranial vessels at the level of the 1st
      vertebra. Average flows were calculated for regions temporally correlated (0.3 <
      or = Rthreshold < or = 0.95) to user defined seed points and their 3 x 3
      neighbours. RESULTS: Arterial CBF averaged 710ml/min, with low variability (+/-
      4%/17%, intra-individual/group CV respectively) and was the only flow to respond
      significantly to 5%/mmHg CO2. Venous outflow was much smaller (298ml/min +/- 10%/
      72%), possibly due to the weak venous pulse and variable venous anatomy. Average
      CSF flows exceeded the classical 0.4ml/min CSF production rate and were highly
      variable--aqueduct: 0.6ml/min (+/- 50%/93%), foramen magnum: -2.7ml/min (+/-
      158%/226%). CONCLUSIONS: This preliminary analysis identified procedural steps
      that can improve the accuracy and repeatability of MR flow measurements, but the
      process remains user-dependent for the weakly pulsatile foramen magnum CSF and
      venous flows where variability remains a significant confound even to relatively
      large perturbations such as CO2 administration.

PMID- 19388328
TI  - Motor trephine syndrome: a mechanistic hypothesis.
AB  - BACKGROUND: In our neurotrauma practice, "motor trephine syndrome" was defined as
      a contralateral monoparesis that developed as a delayed and reversible
      complication in patients treated with decompressive hemicraniectomy for traumatic
      brain injury (TBI). The goal of this study was to define causal factors
      associated with this syndrome. METHODS: We retrospectively reviewed clinical
      records and imaging studies of all patients undergoing decompressive
      hemicraniectomy followed by cranioplasty repair in our comprehensive database of
      TBI patients. Detailed analysis of motor function from the time of injury to 6
      months following cranioplasty repair identified three patterns of motor recovery.
      RESULTS: Blossoming of contusions, CSF circulation dysfunction, and longer times
      to cranioplasty repair were strongly associated with "motor trephine syndrome".
      We hypothesize that "motor trephine syndrome" arises from decompensated CSF flow
      with transgression of CSF fluid and edema into brain parenchyma, together with
      associated decrements in cerebral blood flow. CONCLUSION: Prior contusion injury,
      decreased skull resistance with large hemispheric decompressions, and longer
      intervals to cranioplasty repair facilitate transparenchymal flow of CSF and
      edema. "Motor trephine syndrome" is rapidly reversible following cranioplasty
      repair. CSF and edema fluid changes within the parenchyma and CBF normalize,
      coincident with improvements in the patient's motor function, upon replacement of
      the bone.

PMID- 19388329
TI  - Biomechanical modeling of decompressive craniectomy in traumatic brain injury.
AB  - BACKGROUND: Decompressive craniectomy is the final phase in the graded scheme of
      critical care management of refractory raised intracranial pressure following
      severe traumatic brain injury. We aim to define the optimal size for
      decompressive craniectomy so that a good balance is achieved between reduction of
      raised ICP and the extent of trans-calvarial herniation. Provision of such
      quantitative data will also allow for improved data comparison in clinical trials
      addressing the surgical management of severe head injury. METHODS: In this study,
      we utilize a finite element mesh model and focus on the effect of size of both
      unilateral and bifrontal decompressive craniectomy on intracranial pressure and
      brain herniation. FINDINGS: The finite element mesh model is able to effect
      modeling of brain deformation and intracranial pressure changes following both
      unilateral fronto-parietal-temporal and bifrontal decompressive craniectomy.
      CONCLUSIONS: Finite element mesh modeling in the scenario of reafractory raised
      intracranial pressure following severe head injury may be able to guide the
      optimal conduct of decompressive surgery so as to effect a reduction in
      intracranial pressure whilst minimizing trans-calvarial brain herniation.

PMID- 19388330
TI  - Coupling of sagittal sinus pressure and cerebrospinal fluid pressure in
      idiopathic intracranial hypertension--a preliminary report.
AB  - BACKGROUND: Narrowing of the cranial dural venous sinuses has been implicated as
      contributing to elevated intracranial pressure in idiopathic intracranial
      hypertension [IIH]. Such narrowing may be either a fixed stenosis or secondary to
      raised ICP. We have investigated whether narrowing of the venous sinuses may
      reflect direct coupling between cerebrospinal fluid pressure and sagittal sinus
      pressure. METHODS: Nine patients with the clinical features of IIH [8F, 1M; mean
      age 41 (range 22-55)] were studied as part of their standard clinical
      investigations by simultaneous lumbar CSF infusion study and direct retrograde
      cerebral venography whereby a catheter is placed within the sagittal sinus under
      fluoroscopic guidance. FINDINGS: In all cases, both CSF pressure (Pcsf) and
      sagittal sinus pressure (Pss) were elevated with Pcsf slightly exceeding Pss
      (27.0 +/- 2.3 mm Hg. 25.2 +/- 7.5 mm Hg; difference P = 0.026; correlation R =
      0.97, P = 0.0032). There was a gradient of pressure along the sagittal and
      transverse sinuses. CSF infusion provoked rises in both Pcsf and Pss (R = 0.97, P
      < 0.0007). During drainage of CSF after the test (8 cases), Pcsf decreased to
      values lower than Pss (-3.26 +/- 3.9 mm Hg; P = 0.0097). There was excellent
      correlation between slow waves of Pcsf and Pss (mean R = 0.9) and between
      baseline pulse amplitudes of both pressures (R = 0.91; P = 0.03). CONCLUSIONS: In
      the 9 patients studied with IIH, Pcsf and Pss were coupled both statically (mean
      values) and dynamically (vasogenic components). During drainage, both pressures
      decreased until probably central venous pressure was reached and then Pcsf
      decreased further while Pss remained constant. This suggests that, in many cases
      of IIH, there is functional obstruction of venous outflow through the dural
      sinuses. Raised Pcsf partly obstructs venous sinus outflow, thereby increasing
      Pss which, in turn, leads to a further rise in Pcsf, et sequor. This vicious
      cycle can be interrupted by draining CSF.

PMID- 19388331
TI  - The measurement of brain tissue stiffness in-vivo.
AB  - BACKGROUND: There is considerable interest in surgical decompression as a
      management strategy (RescueICP) for intractable intracranial hypertension. After
      such an operation measurements of intracranial pressure (ICP) and thus cerebral
      perfusion pressure (CPP) become less meaningful. Measurements of the
      biomechanical properties of the brain may be one measure capable of detecting
      changing status of such patients. However these properties of the brain are
      neither documented or well understood. We have developed an indentation probe
      capable of making measurements of human brain stiffness. METHOD: The device
      consists of an indenting tip of depth 2 mm and diameter 12 mm surrounded by an
      annular body of 20 mm diameter. Measurements are made by two load cells,
      connected through interface electronics to a laptop computer. FINDINGS:
      Laboratory measurements show the probe to provide accurate and repeatable
      measurements over a range of zero to 10N. Inter-operator variability from six
      healthcare professionals had a coefficient of variance of 8.75%. Measurements
      obtained during surgery from a patient undergoing tumour resection were towards
      the lower end of the device's measurable range. CONCLUSIONS: We have determined
      that this indentation device has a linear response and that the inter- and intra
      operator variability is low. Although the device is still in an early stage of
      development, preliminary results during intracranial surgery demonstrate that
      this device is capable of measuring in-vivo tissue stiffness. Further work is
      required to derive a quantitative "stiffness index" from the two load curves. In
      addition a standard operation method is required so that consistent and
      repeatable measurements are made. The device may be of value in assessing
      patients after decompressive craniectomy.

PMID- 19388332
TI  - Changes in brain biochemistry and oxygenation in the zone surrounding primary
      intracerebral hemorrhage.
AB  - BACKGROUND: While the management of primary intracerebral hemorrhage (ICH)
      remains controversial, there remains a subset of patients that undergo clot
      evacuation. This study aims to characterize brain physiology and biochemistry
      after surgery for this condition. METHODS: Thirty-six consecutive patients
      requiring ventilation for primary ICH had intracranial pressure (ICP), tissue
      oxygenation (PbO2) and cerebral microdialysis (CMD) monitoring. 28 patients with
      a Glasgow Outcome Score (GOS) of 1-3 formed group 1 while 5 patients with a GOS
      of 4-5 formed group 2. The control group consisted of 3 patients managed
      conservatively without surgery. FINDINGS: The mean PbO2 (24.5 +/- 20.8 mmHg) was
      higher in the patients in group 1 (poor outcome) compared with those in the
      control group (13.6 +/- 9.0 mmHg) (p < 0.001). Compared to patients in group 2,
      the patients in group 1 also had a higher PbO2 (p = 0.02) together with worse
      levels of lactate/pyruvate (L/P) ratio and glycerol (p < 0.001). In all 3 groups,
      ICP reduction to < 20 mmHg was achieved together with a return to of pressure
      reactivity (PRx) to < 0.3. CONCLUSIONS: In spontaneous ICH, derangements in the
      perilesional tissue demonstrated by local techniques of PbO2 monitoring and CMD
      are not seen in global indices such as the PRx.

PMID- 19388333
TI  - Prediction of early mortality in primary intracerebral hemorrhage in an Asian
      population.
AB  - BACKGROUND: Primary intracerebral hemorrhage accounts for the relative minority
      of all strokes and yet is more fatal and disabling. Various prognostic models for
      mortality and functional outcome following primary intracerebral hemorrhage have
      been proposed, however there is little data which focuses on a multi-racial
      population profile characteristic of communities in South-East Asia. A reliable
      grading scale for this condition will allow for accurate risk stratification,
      treatment selection, resource allocation and possibly also aid in the definition
      of common enrollment criteria for clinical trials. METHODS: This study
      investigates an Asian population of primary intracerebral hemorrhage patients and
      defines using a variety of data mining techniques the clinical variables that
      significantly impact on early mortality. The models produced are then compared to
      ascertain which one optimally predicts this outcome. FINDINGS: Past history of
      stroke, known atrial fibrillation, use of warfarin, glucose level, presenting
      Glasgow Coma Scale (GCS) and pupil abnormality, post-resuscitation GCS and pupil
      abnormality, initial international normalized ratio (INR) and prothrombin time
      (PT) results, vomiting, seizure, total volume of clot, ventricular extension and
      hydrocephalus were significantly associated with early mortality. Logit with
      backward elimination showed that only age, presenting GCS, 1st INR result and
      total volume of clot were significantly associated with mortality in the final
      multivariate model. The use of the other data mining techniques yielded
      comparable results. CONCLUSIONS: The predictors for early mortality and poor
      outcome in primary intracerebral hemorrhage are similar in Asian and Western
      populations.

PMID- 19388334
TI  - Ischemic events after carotid interventions in relationship to baseline
      cerebrovascular reactivity.
AB  - BACKGROUND: We aimed to investigate whether baseline cerebrovascular reactivity
      could predict subsequent ischemic event after intervention and identify the
      patient group for more aggressive medical and interventional management
      paradigms. METHODS: Patients with more than 70% cervical carotid stenosis (from
      ultrasonography) were reviewed. Patients, who had baseline cerebrovascular
      reactivity test before intervention and had either carotid endarterectomy (CEA)
      or carotid angioplasty and stenting (CAS) performed, were recruited for analysis.
      Transcranial Doppler ultrasonography was used to examine the reactivity of the
      middle cerebral artery in response to 5% carbon dioxide in oxygen. The mean
      follow up period was 66 months. FINDINGS: Twenty-six patients had symptomatic
      carotid stenosis and ten patients had asymptomatic carotid stenosis. There were
      four subsequent ischemic events during follow up. None of the nine patients with
      impaired baseline ipsilateral cerebrovascular reactivity had subsequent ischemic
      event. CONCLUSIONS: In this current study, impaired baseline cerebrovascular
      reactivity did not predict the subsequent stroke risk after carotid intervention.
      Cerebrovascular reactivity testing may not serve as an indicator for aggressive
      medical and surgical treatments.

PMID- 19388335
TI  - Effect of increased intracranial pressure on cerebral vasospasm in SAH.
AB  - INTRODUCTION: Increased ICP is common and might precipitate cerebral vasospasm
      (VSP)-induced ischemic events in aneurysmal SAH (ASAH).Our objective was to
      determine if there is an association between increased ICP and transcranial
      colour coded Doppler-angiographic VSP (TCCD-A VSP) in relation to delayed
      neurological deficit (DND) and poor outcome. METHODS: A retrospective study was
      undertaken in 30 patients who were status-post clipping of a ruptured anterior
      circulation aneurysm causing subarachnoid hemorrhage. ICP monitoring, post
      operative MCA/A1 flow velocity measurements, and post-operative angiography were
      evaluated, with clinical follow up for at least 3 months. Statistical testing was
      done using a Chi- square analysis between ICP > = 30 mmHg, CPP < = 70 mmHg, TCCD
      A VSP and DND and poor outcome. FINDINGS: Mean ICP was 34.2 mmHg and mean CPP was
      71.3 mmHg. ICP > = 30 mmHg occurred in 56.7%. of patients and CPP < = 70 mmHg
      occurred in 36.7%. TCCD-A VSP, DND and poor outcome occurred in 56.7%, 60% and
      33% of patients respectively. Overall ICP > = 30 mmHg was significantly related
      to TCCD-A VSP (p value = 0.046) but not with DND or poor outcome. CPP < = 70 mmHg
      had no significant relationship with TCCD-A VSP, DND or poor outcome. TCCD-A VSP
      was significantly related to DND (p value = 0.00018) but not to poor outcome. The
      combination of TCCD-A VSP and ICP > = 30 mmHg was significantly related to poor
      outcome (p value = 0.015), but the combination of TCCD-A VSP with CPP < = 70 mmHg
      was not. CONCLUSIONS: Increased ICP, not decreased CPP, was related to VSP. The
      combination of TCCD-A VSP and increased ICP was predictive of poor outcome.
      Management of acute ASAH should include reduction of increased ICP especially
      when there is concomitant TCCD-A VSP.

PMID- 19388336
TI  - Cerebral blood flow thresholds predicting new hypoattenuation areas due to
      macrovascular ischemia during the acute phase of severe and complicated
      aneurysmal subarachnoid hemorrhage. A preliminary study.
AB  - BACKGROUND: Focal ischemia may affect patients with aneurysmal subarachnoid
      hemorrhage (SAH), and the potential evolution of cerebral infarction may greatly
      influence the patients' outcome. The aim of the study was to assess the values of
      regional cortical cerebral blood flow (rCBF) thresholds predictive for ischemia
      during the acute phase of SAH. METHODS: In 34 patients affected by poor grade or
      complicated SAH, 52 pairs of Xenon-CT (Xe-CT) studies of regional CBF were
      analyzed, in which the follow-up Xe-CT study was obtained no later than 72 hours
      after the baseline study. Corresponding cortical ROIs were placed in the
      perimeter of the cortex on both the Xe-CT studies. A blinded, experienced
      neuroradiologist classified for each ROI, the development of a new
      hypoattenuation at the unenhanced CT images included in the follow-up Xe-CT,
      while another independent investigator collected rCBF levels of the ROI in the
      baseline Xe-CT study. FINDINGS: New hypoattenuation developed in 3.94% of the
      ROIs in the paired follow-up Xe-CT studies, and these evolving ROIs were
      associated with a lower rCBF in baseline Xe-CT. However, the positive predictive
      value of rCBF levels for the development of new hypoattenuation was only
      moderately predictive (28.3%) for very low physiological values (5 ml/100gr/min).
      CONCLUSIONS: The results suggest that there is no absolute rCBF threshold
      ofischemia in severe and complicated SAH patients and that the rCBF values are
      only moderately predictive at levels lower than previously described.

PMID- 19388337
TI  - Hyperbaric oxygen preconditioning activates ribosomal protein S6 kinases and
      reduces brain swelling after intracerebral hemorrhage.
AB  - BACKGROUND: New protein synthesis is key to ischemic tolerance induced by
      preconditioning and ribosomal protein S6 kinases (p70 S6 K) are important enzymes
      in protein synthesis. Hyperbaric oxygen preconditioning (HBOP) reduces ischemic
      brain damage. This study investigated if HBOP can activate p70 S6 K and increase
      new protein synthesis and if HBOP induces brain tolerance against brain swelling
      after intracerebral hemorrhage (ICH). METHODS: There were two parts of the
      studies. 1) Rats received five consecutive sessions of HBOP. Twenty-four hours
      after HBOP, the rats had an ICH and were sacrificed one or three days later for
      brain edema measurement. 2) Rats received five sessions of HBOP or control
      pretreatment and were sacrificed for Western blot analysis and
      immunohistochemistry of activated p70 S6 K and heme oxygenase-1 (HO-1). FINDINGS:
      Five sessions of HBOP significantly reduced brain edema in the ipsilateral basal
      ganglia after ICH. Western blot analysis showed that HBOP activated p70 S6 K and
      increased HO-1 levels in the basal ganglia. Strong activated p70 S6 K
      immunoreactivity was also found in the basal ganglia. CONCLUSIONS: Our results
      suggest activation of p70 S6 K may have a role in heat shock protein synthesis
      after HBOP and may contribute to HBOP-induced brain protection.

PMID- 19388338
TI  - Stroke with subarachnoid hemorrhage: assessment of cerebrovascular pressure
      regulation and simulated cerebrovascular resistance.
AB  - BACKGROUND: Monitoring methods designed to assess cerebrovascular regulation and
      increased cerebrovascular resistance (CVR) of patients with subarachnoid
      hemorrhage (SAH) would facilitate therapeutic intervention and potentially reduce
      secondary complications. The aim of this study was to assess changes of
      cerebrovascular regulation and CVR by evaluating changes of cerebrovascular
      pressure transmission in patients with SAH. METHODS: Admission Hunt-Hess grades,
      Fisher scores, Glasgow Outcome Scores (GOS) at 6 months, and pressure recordings
      were obtained from 20 patients. Biomechanical models of cerebrovascular pressure
      transmission were constructed over one-minute intervals for the initial and final
      two hours of post-hemorrhage monitoring. FINDINGS: Classified according to the
      GOS score at 6 months, eight patients died (GOS 1), five were severely disabled
      (GOS 3), and seven patients were moderately disabled (GOS 4). During the initial
      monitoring period 100%, 80%, and 28.6% of groups with GOS 1, 3, and 4
      demonstrated impairment of cerebrovascular regulation; whereas, in the final
      monitoring period 100%, 100%, and 14.3% respectively demonstrated impairment.
      Between monitoring periods, simulated CVR (sCVR) significantly increased (p <
      0.001) for patients with GOS 1 and 3 and decreased for those with GOS 4 with mean
      resistance for the latter group significantly lower (p < 0.001) than other means.
      CONCLUSIONS: Loss of cerebrovascular regulation and increased sCVR were observed
      in SAH patients with poor outcome.

PMID- 19388339
TI  - Effects of melatonin in early brain injury following subarachnoid hemorrhage.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease
      that is associated with significant morbidity and mortality. There is substantial
      evidence to suggest that oxidative stress is significant in the development of
      acute brain injury following SAH. Melatonin is a strong antioxidant that has low
      toxicity and easily passes through the BBB. Previous studies have shown that
      melatonin provides neuroprotection in other models of CNS injury. METHODS: This
      experiment evaluates melatonin as a neuroprotectant against early brain injury
      following SAH. The endovascular perforation model of SAH was performed in male
      Sprague Dawley rats followed by the administration of melatonin two hours after
      the insult. Mortality and brain water content were assessed 24 after SAH.
      FINDINGS: A significant reduction in 24 h mortality was seen following treatment
      with 150 mg/kg of melatonin. Brain water content was evaluated in the high dose
      treatment group to see if a reduction in brain edema was associated with reduced
      mortality. High dose melatonin tended to reduce brain water content following
      SAH. CONCLUSIONS: Large doses of melatonin significantly reduced mortality and
      brain water content in rats following SAH.

PMID- 19388340
TI  - Decompressive craniectomy for hemispheric infarction: predictive factors for six
      month rehabilitation outcome.
AB  - BACKGROUND: Decompressive craniectomy after hemispheric infarction has been shown
      to reduce mortality and functional outcome in selected patients. However, the
      optimal timing for surgery and patient most likely to benefit from this
      procedures was not known. We aimed to determine possible factors predictive of
      outcome following decompressive craniectomy for ischemic infarction from review
      of oneurological outcome in our patients at six months. METHODS: We
      retrospectively reviewed 21 patients who underwent decompressive craniectomy for
      hemispheric infarction over a three year period in a regional neurosurgical
      center in Hong Kong. All patients were recruited subsequently for active in
      patient rehabilitation, when suitable. FINDINGS: The median age was 53 and the
      male to female ration was 1:3. Four patients (19%) achieved independent activity
      of daily living at six months after rehabilitation. Neither early surgery, within
      24-48 hours after admission, nor side of infarction correlated with six month
      neurological outcome. All four patients with favourable neurological outcome at
      six month demonstrated favourable clinical improvement even at one month.
      CONCLUSIONS: Early decompressive hemicraniectomy is not predictive of
      neurological outcome, determined by Glasgow outcome score, at six months (P =
      1.00, NS).

PMID- 19388341
TI  - Effects of temperature changes on cerebral biochemistry in spontaneous
      intracerebral hematoma.
AB  - BACKGROUND: Fever worsens outcome in acute brain injury, presumably by
      accelerating secondary damage. Improved understanding of the pathophysiological
      processes that occur in spontaneous intracerebral hemorrhage (ICH) may help to
      determine if controlled normothermia might be of clinical benefit. METHODS: In
      this prospective observational study over a period of 18 months at the National
      Neuroscience Institute, Singapore, we examined the effects of temperature changes
      on brain biochemistry and tissue oxygenation in 25 consecutive patients with
      spontaneous primary putaminal hemorrhage. The patients were divided into 3 groups
      according to the mean brain temperature over a 72-hour monitoring period
      following surgery and standard medical measures to control post-operative brain
      swelling and secondary injury. FINDINGS: Patients that become spontaneously
      hypothermic with a mean brain temperature of less than 36 degrees centigrade
      (degrees C) had greater impairment in brain biochemistry as reflected by the
      worst brain lactate/pyruvate (L/P) ratio, glutamate and glucose dialysates. Brain
      tissue oxygenation, on the other hand, was highest and within normal limits in
      these spontaneously hypothermic patients. The hyperthemic group had similar L/P
      ratio, glycerol and glutamate levels when compared to the normothermic group. The
      glucose levels were found to be significantly different in all 3 groups.
      CONCLUSIONS: Extremes of temperature in spontaneous ICH, in particular-
      spontaneous hypothermia with a mean brain temperature of less than 36 degrees C,
      are associated with a poor outcome. Cerebral microdialysis can be used to detect
      these detrimental changes that occur.

PMID- 19388342
TI  - Increased levels of CSF heart-type fatty acid-binding protein and tau protein
      after aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Heart-type Fatty Acid-Binding Protein (H-FABP) and tau protein (tau)
      have been shown to be novel biomarkers associated with brain injury and,
      therefore, they could represent a useful diagnostic tool in patients with
      subarachnoid hemorrhage (SAH). The goal of this study was to measure H-FABP and
      tau in cerebrospinal fluid (CSF) following SAH to test the hypothesis that a
      relationship exists between SAH severity and H-FABP/tau values. METHODS: Twenty
      seven consecutive SAH patients admitted to our ICU were studied. Serial CSF
      samples were obtained in every patient starting on the day of SAH and daily for
      up to 2 weeks post-SAH. H-FABP/tau levels were measured by enzyme-linked
      immunosorbent assay. RESULTS: Patients with severe SAH showed significantly
      higher peak levels of H-FABP and tau compared to mild-SAH patients (FABP: p =
      0.02; tay: p = 0.002). In addition the peak concentrations of H-FABP and tau in
      CSF from SAH patients correlated significantly with Glasgow Coma Scale motor
      score (H-FABP: Spearman r = -0.52, p = 0.006; tau: Spearman r = -0.63, p =
      0.0004). Based on outcome at discharge from the hospital, patients were
      categorized into survivors and non-survivors. Peak concentrations of both
      proteins in the non-survivors group were significantly higher than in the
      survivors. CONCLUSIONS: H-FABP and tau CSF levels are proportional to SAH
      severity and may be novel biomarkers that can be used to predict the severity of
      outcome following clinical SAH.

PMID- 19388343
TI  - DNA vaccination against neurite growth inhibitors to enhance functional recovery
      following traumatic brain injury.
AB  - BACKGROUND: Myelin-associated proteins contribute to failure of axon regeneration
      in the injured central nervous system of the adult. METHODS: In this study, we
      employed a recombinant DNA vaccine encoding the myelin-derived inhibitors NogoA,
      myelin-associated glycoprotein (MAG) and tenascin-R (TnR), so as to effect the
      production of antibodies against these myelin-related antigens, in a rodent head
      injury model and ascertained its potential for promoting axonal plasticity and
      functional recovery. Adult rats underwent lateral fluid percussion at the left
      sensorimotor cortex (SMC) and treatment with the DNA vaccine before or after
      injury. Behavioral tests and neuroanatomical tract tracing was carried out.
      FINDINGS: The vaccinated rats showed improved corticorubral plasticity and
      functional recovery compared to control groups. CONCLUSIONS: This suggests that a
      DNA vaccination approach may provide a promising strategy for promoting repair
      after traumatic brain injury.

PMID- 19388344
TI  - Ischemic blood-brain barrier and amyloid in white matter as etiological factors
      in leukoaraiosis.
AB  - BACKGROUND: Pathology of white matter, which is observed in ischemic brain,
      indicates that similar processes contribute to Alzheimer's disease development.
      These injuries have been seen in the subcortical and periventricular regions.
      Periventricular white matter changes in ischemic and Alzheimer's disease brain,
      referred to as leukoaraiosis, are responsible for changes in memory, cognition
      and behavior. It is not clear whether the blood-brain barrier in ischemic
      periventricular white matter is altered in aged animals. METHODS: We studied
      blood-brain barrier changes with amyloid precursor protein staining around blood
      brain barrier vessels. Rats were made ischemic by cardiac arrest. Blood-brain
      barrier insufficiency, accumulation of amyloid precursor protein and platelets
      around blood-brain barrier vessels were investigated in ischemic periventricular
      white matter up to 1-year survival. FINDINGS: Ischemic periventricualr white
      matter demonstrated enduring blood-brain barrier changes. Toxic fragments of
      amyloid precursor protein deposits were associated with the blood-brain barrier
      vessels. Moreover our investigation revealed platelet aggregates in- and outside
      blood-brain barrier vessels. Toxic parts of amyloid precursor protein and
      platelet aggregates correlated very well with blood-brain barrier permeability.
      CONCLUSIONS: Progressive injury of the ischemic periventricular white matter may
      be caused not only by a degeneration of neurons destroyed during ischemia but
      also by damage in blood-brain barrier. Chronic ischemic blood-brain barrier
      insufficiency with accumulation of toxic components of amyloid precursor protein
      in the periventricular white matter perivascular space, may gradually over a
      lifetime, progress to leukoaraiosis and finally to severe dementia.

PMID- 19388345
TI  - Matrix metalloproteinase inhibition attenuates brain edema after surgical brain
      injury.
AB  - BACKGROUND: Neurosurgical operations can result in inevitable brain injury due to
      the procedure itself. This surgical brain injury (SBI) can cause post-operative
      complications such as brain edema following blood-brain barrier (BBB) disruption
      leading to neurological deficits. METHODS: We tested whether inhibition of matrix
      metalloproteinases (MMPs) 9 and 2 provided neuroprotection against SBI. A rodent
      SBI model, which involves a partial frontal lobe resection, was used to evaluate
      two treatment regimens of MMP inhibitor-1 (inhibitor of MMP-9 and MMP-2); a
      single dose (5 mg/kg, pretreatment) and daily dose treatment (5 mg/kg x 3, pre-
      and post-treatment). Postoperative assessment at different time periods included
      brain water content (brain edema), immunohistochemical analysis, zymography for
      MMP enzymatic activity, and neurological assessment. FINDINGS: The results
      indicate that SBI caused localized edema around the site of surgical resection
      with concomitant increase in MMP-9 and MMP-2 activity. Both treatment regimens
      with MMP inhibitor-1 decreased brain edema and attenuated the rise in MMP-9 and
      MMP-2 activity. An increased expression of MMP-9 was also seen in the neurons and
      neutrophils in the affected brain tissue at the periphery of surgical resection.
      CONCLUSIONS: The study suggests a potential role for MMP inhibition as
      preoperative therapy before neurosurgical procedures.

PMID- 19388346
TI  - Thrombin enhances glioma growth.
AB  - BACKGROUND: Our previous studies have demonstrated that argatroban, a specific
      thrombin inhibitor, reduces brain edema and neurological deficits in rat glioma
      models. The present study investigated whether or not thrombin enhances glioma
      growth in vivo and in vitro. METHODS: There were two parts in this study. In the
      first part, rat C6 glioma cells were treated with or without thrombin. These
      cells were then injected into the right caudate of adult male Fischer 344 rats.
      Rats underwent behavioral testing prior to sacrifice 12 days later for tumor mass
      measurement. In the second part, C6 cells were incubated in serum-free medium for
      24 hours and then treated with thrombin with or without argatroban, a thrombin
      inhibitor. DNA synthesis was examined using a 5-bromo-2'-deoxyuridine (BrdU)
      ELISA kit. Cell proliferation was determined using a 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl-tetrazolium bromide (MTT) assay. FINDINGS: Treatment of C6 cells
      with thrombin prior to intracerebral implantation resulted in a larger tumor mass
      and worse neurological deficits at dayl2. In vitro, thrombin increased DNA
      synthesis in C6 glioma cells, and this effect was blocked by argatroban. MTT
      assay showed that thrombin significantly increased glioma cell proliferation in
      vitro. CONCLUSIONS: In summary, thrombin enhances C6 glioma growth in vivo and
      cell proliferation in vitro suggesting that thrombin may be a target of glioma
      therapy.

PMID- 19388347
TI  - The antioxidant effects of melatonin in surgical brain injury in rats.
AB  - BACKGROUND: Surgical brain injury (SBI) to normal brain tissue can occur as
      inevitable sequelae of neurosurgical operations. SBI can contribute to post
      operative complications such as brain edema following blood-brain barrier (BBB)
      disruption leading to neurological deficits. Melatonin is a commonly used drug
      with known antioxidant properties and neuroprotective effects in experimental
      animal studies (Chen et al., J Pineal Res 41:175-182, 2006; Chen et al., J Pineal
      Res 40(3):242-250, 2006; Cheung, J Pineal Res 34:153-160, 2003; Lee et al., J
      Pineal Res 42(3):297-309, 2007; Reiter et al., Exp Biol Med (Maywood) 230(2):104
      117, 2005). METHODS: We tested different concentrations of melatonin (5 mg/kg, 15
      mg/kg and 150 mg/kg) administered 1 hour before surgery for neuroprotection
      against SBI using a rodent model. Post-operative assessment included brain water
      content (brain edema), lipid peroxidation assays (oxidative stress), and
      neurological assessment. FINDINGS: The results showed a trend in decreasing brain
      edema with lower doses of melatonin (5 mg/kg and 15 mg/ kg), however, high
      concentration of melatonin (150 mg/kg) significantly increased brain edema
      compared to all other groups. This deleterious effect of high-dose melatonin was
      also observed in lipid-peroxidation assay wherein lower-dose melatonin (15 mg/kg)
      attenuated oxidative stress, but high-dose melatonin (150 mg/kg) increased
      oxidative stress as compared to vehicle-treated group. Furthermore, high-dose
      melatonin also worsened neurological outcomes compared to other groups whereas;
      the low-dose melatonin group (15 mg/kg) showed some improved neurological
      parameters. CONCLUSIONS: The study suggests that low-dose melatonin may provide
      neuroprotective effects against SBI. Further studies are needed to confirm this.
      More importantly, the findings of the study stress the need to carefully reassess
      safety issues with high doses of melatonin, which is considered to be a
      practically non-toxic drug.

PMID- 19388348
TI  - Dymanics of matrix-metalloproteinase 9 after brain trauma--results of a pilot
      study.
AB  - BACKGROUND: Secondary brain injury contributes to poor outcome for patients
      sustaining brain trauma. Matrix metalloproteinase-9 (MMP-9) is a potential
      marker, as well as effector of secondary brain injury. This enzyme degrades
      components of extracellular matrix, and thus it can contribute to blood-brain
      barrier disruption. METHODS: We studied dynamics of MMP-9 in jugular venous blood
      of 15 patients sustaining either an isolated head injury or a head injury as a
      part of major trauma, and requiring intensive care (Glasgow Coma Scale <8 at the
      time of admission). Blood samples were taken at the 1st, 3rd and 5th day, levels
      of MMP-9 in plasma were assessed using ELISA. Outcome quality was assessed at the
      time of discharge from our hospital. FINDINGS: Our results show an increase of
      MMP-9 levels on the 1st day after the brain trauma, followed by a drop on the 3rd
      day and a rise on day 5. This biphasic time-course was observed in all patients,
      but no statistically significant differences between each group (major trauma vs.
      isolated brain trauma, good outcome vs. poor outcome) were found. CONCLUSIONS:
      Initially increased MMP-9 levels in the 1st posttraumatic day is probably related
      to transient blood-brain barrier dysruption. The decrease of MMP-9 levels
      observed on the 3rd day can be explained by restoration of blood-brain barrier
      integrity and its reduced permeability. The second rise of MMP-9 levels observed
      in the 5th day probably indicates a developing secondary brain injury during
      which MMP-9 is produced in the brain as a part of an inflammatory response.
      RESULTS: of our study suggest that MMP-9 could play an important role in
      pathogenesis of secondary brain injury.

PMID- 19388349
TI  - Experimental subarachnoid hemorrhage in the rat: influences of nimodipine.
AB  - BACKGROUND: Traumatic subarachnoid hemorrhage is a common finding following
      traumatic brain injury. Clinical studies revealed a positive influence of
      Nimodipine. However, till now no experimental studies have been performed. The
      aim of the present study was to determine the influence of early Nimodipine
      administration on outcome and histological findings in the rat: METHODS: Diffuse
      brain injury was produced in Sprague-Dawley rats using a brass weight falling
      from a predetermined height. Traumatic subarachnoidal hemorrhage was produced by
      administration of heparin before the injury. A total number of 52 animals were
      divided in 4 groups. FINDINGS: Mortality increased following administration of
      heparin. Mortality was not reduced following administration of Nimodipine. The
      histological investigation revealed less cell loss in animals with administration
      of Nimodipine as well as increased GFAP immunoexpression. CONCLUSIONS:
      Administration of Heparin results in a marked traumatic subrachnoidal hemorrhage
      following diffuse traumatic brain injury. Administration of Nimodipine does not
      reduce overall mortality. However, histological investigations indicate a
      positive effect of Nimodipine on cell loss.

PMID- 19388350
TI  - Neuroprotective effect of C1-inhibitor following traumatic brain injury in mice.
AB  - BACKGROUND: The goal of the study was to evaluate the effects of Cl-inhibitor (C1
      INH), an endogenous glycoprotein endowed with multiple anti-inflammatory actions,
      on cognitive and histological outcome following controlled cortical impact (CCI)
      brain injury. METHODS: Male C57B1/6 mice (n=48) were subjected to CCI brain
      injury. After brain injury, animals randomly received an intravenous infusion of
      either C1-INH (15 U either at 10 minutes or 1 hour postinjury) or saline (equal
      volume, 150 microl at 10 min postinjury). Uninjured control mice received
      identical surgery and saline injection without brain injury. Cognitive function
      was evaluated at 4 weeks postinjury using the Morris Water Maze. Mice were
      subsequently sacrificed, the brains were frozen and serial sections were cut.
      Traumatic brain lesion was assessed by dividing the area of the ipsilateral
      hemisphere for the area of the contralateral one at the level of the injured area
      of the brain. FINDINGS: Brain-injured mice receiving C1-INH at 10 min postinjury
      showed attenuated cognitive dysfunction compared to brain-injured mice receiving
      saline (p < 0.01). These mice also showed a significantly reduced traumatic brain
      lesion compared to mice receiving saline (p < 0.01). Mice receiving C1-INH at 1
      hour post injury did not show a significant improvement in either cognitive or
      histological outcome. Conclusions Our results suggest that administration of C1
      INH at 10 minutes postinjury attenuates cognitive deficits and histological
      damage associated with traumatic brain injury.

PMID- 19388351
TI  - Up-regulation of L type amino acid transporter 1 after spinal cord injury in
      rats.
AB  - BACKGROUND: L-type amino acid transporter 1 (LAT1) is proposed to be a major
      nutrient transporter at the blood brain barrier. LAT1 requires the heavy chain of
      4F2 cell surface antigen (4F2hc) for functional expression. METHODS: We
      investigated the expression of this heterodimeric transporter after traumatic
      spinal cord injury in rat by using immunohistochemical and western blot analyses.
      FINDINGS: LAT1 immunoreactivities were up-regulated in the capillary endothelia
      in close to the injury epicenter 24 hours after injury. It reached a peak at 48
      hours after injury, and thereafter decreased. 4F2hc was abundant and unchanged
      all through the time course after SCI. Western blot analysis under reductive and
      non-reductive conditions showed that LAT1 and 4F2hc were conjugated as a
      heterodimeric transporter and the functional regulation was dependent on the
      light chain, LAT1. CONCLUSIONS: We suggest that LAT1 may be transiently
      upregulated as part of the tissue-repair process after traumatic contusion injury
      in the spinal cord.

PMID- 19388352
TI  - Cortical expression of prolactin (PRL), growth hormone (GH) and
      adrenocorticotrophic hormone (ACTH) is not increased in experimental traumatic
      brain injury.
AB  - BACKGROUND: Cerebral cortical expression of the pituitary hormones prolactin
      (PRL) and growth hormone (GH) have reported in ischemic damage. Both hormones may
      be involved in vascular tone regulation and angiogenesis, and growth hormone is
      thought to be neuroprotective while prolactin stimulates astrogliosis. METHODS:
      We examined expression of prolactin, growth hormone and adrenocorticotrophic
      hormone (ACTH) using tissue microarray technology in the controlled cortical
      impact model of traumatic brain injury (TBI). FINDINGS: No increased expression
      of these hormones was seen. CONCLUSIONS: Unlike ischemia, traumatic brain injury
      does not result in up-regulation of the pituitary hormones PRL and GH in cerebral
      cortex.

PMID- 19388353
TI  - Simvastatin attenuates cerebral vasospasm and improves outcomes by upregulation
      of PI3K/Akt pathway in a rat model of subarachnoid hemorrhage.
AB  - BACKGROUND: Cerebral vasospasm is a common sequelae of subarachonoid hemorrhage
      (SAH), however, the mechanism of cerebral vasospasm is still unclear. Recently,
      statins have been shown to have efficacy in ameliorating cerebral vasospasm. The
      present study investigates whether simvastatin attenuates cerebral vasospasm
      after subarachnoid hemorrhage (SAH) via upregulation of the PI3K/Akt pathway.
      METHODS: 47 adult male Sprague-Dawley rats were divided into 6 groups: sham
      operated, SAH treated with vehicle, SAH treated with low dose simvastatin (1
      mg/kg), high dose simvastatin (20 mg/kg), SAH treated with simvastatin plus the
      PI3K inhibitor (wortmannin), and sham-operated plus wortmannin. Simvastatin was
      administered intraperitoneally 30 minutes after SAH created by the standard
      endovascular perforation model. Histological parameters of the ipsilateral
      internal carotid artery (ICA-diameter, perimeter, and wall thickness) and
      neurological score were assessed at 24 hours. FINDINGS: Mortality was reduced to
      zero in both the treated groups as compared to 20% in the vehicle-treated and 36%
      in the simvastatin plus wortmannin-treated groups. The decrease in ICA diameter
      and perimeter observed in vehicle-treated group (203.2 +/- 10.3 microm, 652.7 +/-
      29.0 microm) as compared to sham (259.7 +/- 10.6, 865.4 +/- 39.5) were
      significantly attenuated by high-dose simvastatin (267.4 +/- 8.0, 882.4 +/-
      30.0). The increase in wall thickness (vehicle 29.50 +/- 2.42 microm v/s sham
      9.52 +/- 0.56 microm) was significantly attenuated by both high and low dose
      simvastatin (11.87 +/- 1.56, 19.75 +/- 1.40). These effects of simvastatin were
      blocked with the addition of wortmannin (162.7 +/- 20.6, 528.9 +/- 65.9, 29.19 +/
      1.97). High dose simvastatin improved the neurological deficits after SAH, but
      this was also blocked by wortmannin. CONCLUSIONS: The beneficial effects of high
      dose simvastatin in ameliorating cerebral vasospasm are likely mediated by
      upregulation of the PI3K/Akt pathway.

PMID- 19388354
TI  - HIF-1 alpha inhibition ameliorates neonatal brain damage after hypoxic-ischemic
      injury.
AB  - BACKGROUND: Hypoxia-inducible-factor-1alpha (HIF-1alpha) has been considered as a
      regulator of both prosurvival and prodeath pathways in the nervous system. This
      study was designed to elucidate the role of HIF-1alpha in neonatal hypoxia
      ischemia (HI) brain injury. METHODS: 2-methoxyestradiol (2ME2), a HIF-1alpha
      inhibitor, was tested at different dosages (1.5, 15 and 150 mg/kg) and a
      therapeutic window was tested by administrating 2-methoxyestradiol (15 mg/kg)
      immediately or 3 hours after the induction of a hypoxic ischemic injury. Infarct
      size using TTC staining and brain edema were measured at 48 hours post hypoxia
      ischemia. Blood-brain barrier (BBB) permeability was examined by IgG staining.
      Vascular endothelial growth factor (VEGF) and HIF-1alpha expression and
      distribution were studied by immunohistochemistry and western blotting analysis.
      FINDINGS: 2ME2 exhibited dose-dependent neuroprotection by decreasing infarct
      volume and attenuating brain edema. 2ME2 also attenuated BBB disruption, and
      decreased HIF-1alpha and vascular endothelial growth factor (VEGF) expression.
      The neuroprotection, however, was lost when 2ME2 was administered 3 hours after
      neonatal HI. CONCLUSION: The study shows that the acute inhibition of HIF-1alpha
      is neuroprotective in neonatal hypoxic-ischemic injury by preserving BBB
      integrity and reducing brain edema.

PMID- 19388355
TI  - Simvastatin treatment in surgically induced brain injury in rats.
AB  - BACKGROUND: HMG-CoA reductase inhibitors (Statins) have been shown to reduce
      blood brain barrier (BBB) disruption and improve neurologic outcome in
      cerebrovascular disorders. Brain injury due to neurosurgical procedures can lead
      to post-operative complications such as brain edema and altered neurologic
      function. The objective of this study was to evaluate whether simvastatin reduces
      brain edema by preventing BBB disruption and improves neurologic status after
      surgically-induced brain injury (SBI). METHODS: Animals were pretreated for seven
      days with vehicle or simvastatin i.p. daily, after which they underwent SBI.
      Neurologic evaluation was assessed at 24 hours post-SBI and the animals were
      sacrificed for brain water content calculation and BBB evaluation. FINDINGS:
      Brain water content was significantly increased in the right frontal lobe in all
      SBI groups as compared to the left frontal lobe. There was no significant
      difference in brain water content in the right frontal lobe between simvastatin
      and vehicle treated groups. Evans blue testing did not show a significant
      difference in disruption of the BBB between groups. Neurologic scores were not
      significantly different. CONCLUSIONS: Simvastatin did not reduce brain water
      content, protect the BBB, or improve neurologic scores after SBI.

PMID- 19388356
TI  - 3% hypertonic saline following subarachnoid hemorrhage in rats.
AB  - BACKGROUND: Hypertonic saline (HTS) has been proposed as a treatment after
      aneurysmal subarachnoid hemorrhage (SAH) to minimize ischemic brain injury due to
      its osmotic and rheologic properties. Although the benefits of 7.2% HTS use in
      brain injury have been studied, there is a paucity of data on the use of 3%HTS.
      METHODS: We investigated whether 3%HTS can reduce brain water content and improve
      neurologic function after SAH in the rodent model compared to 0.9% saline
      solution (NS). Neurologic testing was conducted at 24 hours post-SAH prior to
      sacrificing animals for brain water content evaluation. FINDINGS: There was
      significant potentiation of brain water content in the right hemisphere between
      3%HTS and NS groups. The modified Garcia score was not significantly different
      between the two groups; however, the vibrissae-stimulated forelimb placement test
      showed significantly lower scores in the HTS group. 3%HTS does not decrease brain
      edema or improve neurologic deficits as compared to NS. In fact, our study showed
      3%HTS potentiated brain edema and worsened neurologic deficits in the rat SAH
      model. CONCLUSIONS: Given the potential adverse effects of HTS therapies,
      including hyperchloremic acidosis, and the lack of benefit found in our study,
      more investigation is required to evaluate the clinical use of 3%HTS in the
      setting of SAH.

PMID- 19388357
TI  - Effect of traumatic brain injury on cognitive function in mice lacking p55 and
      p75 tumor necrosis factor receptors.
AB  - BACKGROUND: Tumor necrosis factor (TNF)-alpha has been suggested to play both a
      deleterious and beneficial role in neurobehavioral dysfunction and recovery
      following traumatic brain injury (TBI). The goal of this study was to evaluate
      the specific role of tumor necrosis factor (TNF) receptors p55 and p75 in
      mediating cognitive outcome following controlled cortical impact (CCI) brain
      injury by comparing post-traumatic cognitive function in mice with genetically
      engineered deletion of the gene for either p55 (-/-) or p75 (-/-) receptors.
      METHOD: Male C57B1/6 mice (WT, n=29), and mice genetically engineered to delete
      p55 TNF (p55 (-/-), n=8) or p75 TNF (p75 (-/-), n=23) receptors were used. They
      were anesthetized with intraperitoneal (i.p.) administration of sodium
      pentobarbital (65 mg/kg) and subjected to CCI brain injury of moderate severity.
      Sham-injured control mice were anesthetized and surgically prepared similarly but
      they received no impact. Assessment of mRNA expression of inflammatory,
      proapoptotic and antiapoptotic genes was done by real time-polymerase chain
      reaction (RT-PCR). Cognitive outcome was evaluated at 4 weeks postinjury using
      the Morris water maze (MWM). FINDINGS: mRNA expression of inflammatory,
      proapoptotic and antiapoptotic genes prior to TBI did not reveal any baseline
      difference between p55 and p75 (-/-) mice. WT mice showed greater baseline
      expression of inflammatory genes. The learning ability of p55 (-/-) brain-injured
      mice was significantly better than that observed in p75 (-/-) brain-injured mice
      (p < 0.05). Cognitive learning in WT control mice fell between the p55 (-/-) and
      p75 (-/-) mice. CONCLUSIONS: These data suggest that TNF-alpha may both
      exacerbate cognitive dysfunction via p55 receptor and attenuate it via p75
      receptor.

PMID- 19388358
TI  - Brain contusions induce a strong local overexpression of MMP-9. Results of a
      pilot study.
AB  - BACKGROUND: Brain contusions are inflammatory evolutive lesions that induce
      intracranial pressure increase and edema, contributing to neurological outcome.
      Matrix metalloproteinases (MMPs) 2 and 9 can degrade the majority of the
      extracellular matrix components, and are implicated in blood-brain barrier
      disruption and edema formation. The aim of this study was to investigate MMP-2
      and MMP-9 profiles in human brain contusions using zymography. METHODS: A
      prospective study was conducted in 20 traumatic brain injury patients where
      contusion brain tissue was resected. Brain tissues from lobectomies were used as
      controls. Brain homogenates were analysed by gelatin zymography and in situ
      zimography was performed to confirm results, on one control and one brain
      contusion tissue sample. FINDINGS: MMP-2 and MMP-9 levels were higher in brain
      contusions when compared to controls. MMP-9 was high during the first 24 hours
      and at 48 to 96 hours, whereas MMP-2 was slightly high at 24 to 96 hours. In situ
      zymography confirmed gelatin zymography results. A relation between outcome and
      MMP-9 levels was found; MMP-9 levels were higher in patients with worst outcome.
      CONCLUSIONS: Our results indicate strong time-dependent gelatinase expression
      primarily from MMP-9, suggesting that the inflammatory response induced by focal
      lesions should be considered as a new therapeutic target.

PMID- 19388359
TI  - Shock wave-induced brain injury in rat: novel traumatic brain injury animal
      model.
AB  - BACKGROUND: In blast wave injury and high-energy traumatic brain injury, shock
      waves (SW) play an important role along with cavitation phenomena. However, due
      to lack of reliable and reproducible technical approaches, extensive study of
      this type of injury has not yet been reported. The present study aims to develop
      reliable SW-induced brain injury model by focusing micro-explosion generated SW
      in the rat brain. METHODS: Adult male rats were exposed to single SW focusing
      created by detonation of microgram order of silver azide crystals with laser
      irradiation at a focal point of a truncated ellipsoidal cavity of20 mm minor
      diameter and the major to minor diameter ratio of 1.41 after craniotomy. The
      pressure profile was recorded using polyvinylidene fluoride needle hydrophone.
      Animals were divided into three groups according to the given overpressure: Group
      I: Control, Group II: 12.5 +/- 2.5 MPa (high pressure), and Group III: 1.0 +/-
      0.2 MPa (low pressure). Histological changes were evaluated over time by
      hematoxylin-eosin staining. FINDINGS: Group II SW injuries resulted in
      contusional hemorrhage in reproducible manner. Group III exposure resulted in
      spindle-shaped changes of neurons and elongation of nucleus without marked
      neuronal injury. CONCLUSIONS: The use of SW loading by micro-explosion is useful
      to provide a reliable and reproducible SW-induced brain injury model in rats.

PMID- 19388360
TI  - Modulation of AQP4 expression by the selective V1a receptor antagonist, SR49059,
      decreases trauma-induced brain edema.
AB  - BACKGROUND: Currently, there are no pharmacological treatments available for
      traumatically induced brain edema and the subsequent rise of ICP. Evidence
      indicates that Aquaporin-4 (AQP4) plays a significant role in the pathophysiology
      of brain edema. Previously we have reported that SR49059 reduced brain edema
      secondary to ischemia. We, therefore, examined whether the selective V1a receptor
      antagonist, SR49059, reduces brain edema by modulating AQP4 expression following
      cortical contusion injury (CCI). METHODS: Traumatic brain injury (TBI) was
      produced in thirty-two adult male Sprague-Dawley rats by lateral CCI (6.0 m/sec,
      3 mm depth). Animals were randomly assigned to vehicle (n=16) or SR49059
      treatment (n=16) groups and administered drug (960 microl/hr i.v.) immediately
      after injury over a 5 hr period. Animals were sacrificed for assessment of brain
      water content by Wet/Dry method and AQP4 protein expression by immunoblotting
      expressed as the ratio of AQP4 and Cyclophilin-A densitometries. FINDINGS:
      Elevated AQP4 expression levels and water content were observed on the right
      injured side in both the right anterior (RA) and right posterior (RP) section
      compared to the left non-injured side inclusive of the left anterior (LA) and
      right anterior (RA) sections. The average AQP4 expression levels in contused
      areas for animals receiving SR drug treatment (RA: 1.313 +/- 0.172, RP: 1.308 +/-
      0.175) were significantly decreased from vehicle-treated animals (RA: 2.181 +/-
      0.232, RP: 2.303 +/- 0.370, p = 0.001, p= 0.003). Water content levels on SR
      treatment (78.89 +/- 0.14) was also significantly decreased from vehicle levels
      (80.38 +/- 0.38, p < 0.01) in the traumatized hemisphere. CONCLUSIONS: SR49059
      significantly reduced trauma-induced AQP4 up-regulation in the contused
      hemisphere. Moreover, brain water content was also significantly reduced
      paralleling the AQP4 suppression. These data provide further support that
      vasopressin (AVP) and V1a receptors can control water flux through astrocytic
      plasma membranes by regulating AQP4 expression. Taken in concert, these results
      affirm our laboratories contention that AQP4 can be effectively modulated
      pharmacologically.

PMID- 19388361
TI  - The modulation of aquaporin-4 by using PKC-activator (phorbol myristate acetate)
      and V1a receptor antagonist (SR49059) following middle cerebral artery
      occlusion/reperfusion in the rat.
AB  - BACKGROUND: We have pursued the concept that traumatic brain edema is
      predominantly cellular and that water entry is modulated in part by aquaporins.
      Aquaporin-4 (AQP4) has been shown to play a significant role in cellular edema
      formation. Phorbol myristate acetate (PMA) is a potent PKC activator; purportedly
      involved in modulation of AQP4 activity. Alternatively, AQP4 may be regulated by
      arginine-vasopressin. Administration of the vasopressin antagonist (SR49059)
      reduced brain water content and sodium shift following MCAo. To investigate if
      edema formation is affected by the reduction of AQP4 expression, we utilized PMA
      and SR49059 following middle cerebral artery occlusion model (MCAo), and measured
      AQP4 expression by Western-Blot (WB) techniques. METHODS: Male Sprague Dawley
      rats were randomly assigned to sham (n=4) or MCAo groups (vehicle, PMA or SR49059
      infusion; n=6 each). Each solution was infused for 5 hours, starting 1 hour
      before injury. After a two-hour period of ischemia and two-hour reperfusion,
      animals were sacrificed and brain regions of interest were processed by WB to
      quantify the effect of treatment on AQP4 expression. RESULTS: These studies
      demonstrate that MCAo results in a significant up-regulation of AQP4 on the
      ischemic zone when compared to the contralateral un-injured hemisphere (p < 0.05)
      and that PMA and SR49059 treatment significantly down-regulated AQP4 expression
      compared to the vehicle group (p < 0.05). CONCLUSIONS: These studies support the
      hypotheses that PMA and SR49059 may be useful in reducing cerebral water
      accumulation by modulating AQP4 expression and that pharmacological manipulation
      of AQP4 may emerge as a viable strategy for the reduction of fulminating edema
      following ischemic injury.

PMID- 19388362
TI  - Pro-inflammatory and pro-apoptotic elements of the neuroinflammatory response are
      activated in traumatic brain injury.
AB  - BACKGROUND: The inflammatory response may contribute to cerebral edema, increased
      intracranial pressure and cellular loss in traumatic brain injury (TBI).
      Cytokines are biomarkers of this inflammatory response and new methods allow
      simultaneous measurement of multiple cytokines. METHODS: We examined the IL
      1beta, IL-6, IL-8 and IL-12, TNFalpha, and IL-10 in arterial and jugular blood as
      well as cerebrospinal fluid in patients with severe traumatic brain injury.
      FINDINGS: Multiple cytokines, particularly pro-inflammatory cytokines, are up
      regulated following TBI. Cerebrospinal fluid and arteriovenous differences of
      some of the cytokines suggest production within the central nervous system.
      Antiinflammatory cytokines are not up-regulated. CONCLUSIONS: Cytokine up
      regulation may contribute to the neuroinflammatory reaction that follows
      traumatic brain injury and may contribute to secondary injury.

PMID- 19388363
TI  - Protective effect of hyperbaric oxygen therapy on experimental brain contusions.
AB  - BACKGROUND: We evaluated the effect of hyperbaric oxygen therapy (HBO) on
      experimental brain contusions in rats using magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: Ten Sprague-Dawley rats were investigated at 24 h and 72 h
      after controlled cortical impact injury. One hour after trauma, 5 rats were
      treated for 60 min with 100% oxygen at 2.5 absolute atmosphere (ATA), 5 were kept
      at normobaric room air. MRI was performed longitudinally at 24 h and 72 h after
      injury. Lesion volume was determined in T2 weighted MRI scans. Relative apparent
      diffusion coefficient (ADC) changes were calculated in comparison to the
      contralateral side. RESULTS: Following HBO, T2 lesion volume was smaller at 24 h
      versus controls (63.1 +/- 16.5 mm3 vs. 87.4 +/- 13.8 mm3, p < 0.05), and
      decreased further at 72 h (46.8 +/- 17.8 mm3 vs. 92.5 +/- 13.1 mm3, p < 0.01). At
      24 h, the mean relative ADC change in the lesion area decreased from + 26.8 +/-
      2.3% in controls to + 2.3 +/- 12.2% in HBO animals (p < 0.01). At 72 h, the HBO
      effect on relative ADC values was less when compared to 24 h. DISCUSSION: A 60
      minute exposure to hyperbaric oxygen starting 1 h after impact injury
      significantly attenuated lesion growth and relative increase of ADC values within
      the contused area for up to 72 h. Thus, a "single-shot" HBO treatment seems to
      have long-lasting neuroprotective effects on the contused brain and its penumbra.

PMID- 19388364
TI  - Cancer prevalence in the Canadian population.
AB  - BACKGROUND: The rising numbers of cancer diagnoses, together with improvements in
      survival, have led to increases in the prevalence of cancer in Canada. This
      article provides more precise and detailed estimates of cancer prevalence than
      have been available previously. DATA AND METHODS: Based on incidence data from
      the Canadian Cancer Registry linked with mortality data from the Canadian Vital
      Statistics Death Database, direct estimates of cancer prevalence as of January 1,
      2005 were calculated for an extensive list of cancers, by time since diagnosis,
      age and sex. RESULTS: Two-, five- and ten-year cancer prevalence counts were
      217,089 (675 per 100,000), 454,149 (1,412 per 100,000) and 722,833 (2,248 per
      100,000), respectively. Breast (20.6% of ten-year prevalent cases), prostate
      (18.7%) and colorectal cancer (12.9%) were the most prevalent, together
      accounting for just over half of all cases. Prevalence proportions for all
      cancers combined increased dramatically with age, peaking at ages 80 to 84;
      proportions were higher in females than in males before age 60, and higher in
      males thereafter. INTERPRETATION: Prevalence data tabulated according to type of
      cancer, age and time since diagnoses provide important information about the
      demand for cancer-related health care and social services.

PMID- 19388365
TI  - Income and psychological distress: the role of the social environment.
AB  - BACKGROUND: This article examines the relationship between lower income and the
      risk of experiencing high psychological distress over twelve years. DATA AND
      METHODS: Data from the first 12 years of the longitudinal National Population
      Health Survey (1994/1995 through 2006/2007) were analysed. Proportional hazards
      modelling was conducted to determine whether lower household income was
      associated with a greater risk of experiencing high distress, when adjusting for
      sociodemographic characteristics and baseline health status. It was also used to
      examine the relationship between reporting a stressor and experiencing a
      subsequent episode of distress. RESULTS: Overall, 11% of the initial sample
      experienced at least one episode of high distress during the 12 years of the
      study. Low-income respondents were at a significantly higher risk of becoming
      psychologically distressed, and many of the stressors were associated with a
      significantly higher risk of becoming distressed. Stressors accounted for 22% of
      the relationship between low income and distress for men, and more than a third
      of this relationship for women. INTERPRETATION: Low income is an important risk
      factor for becoming psychologically distressed, and stressors account for part of
      this increased risk.

PMID- 19388366
TI  - The natural history of health-related quality of life: a 10-year cohort study.
AB  - BACKGROUND: Taking account of the impacts of institutionalization and death, this
      study describes the normative trajectories of health-related quality of life
      (HRQL) in Canada as individuals age from mid-to late life. METHODS: A nationally
      representative sample of 7,915 community-dwelling adults aged 40 and older in
      1994/1995 was studied using 10 years of data from the longitudinal National
      Population Health Survey. Growth curve models of HRQL over age were fitted to
      describe the evolution of HRQL. Successive models were tested, first including
      only those living in a household throughout the entire period, then adding those
      who moved to an institution, and finally, including those who had died. RESULTS:
      HRQL remained generally stable until approximately age 70, when it began to
      decline. Excluding individuals when they were institutionalized, or ignoring the
      impact of death resulted in overly optimistic trajectories of HRQL in later
      years. INTERPRETATION: These results demonstrate the importance of following
      individuals into institutions and accounting for death in the production of
      realistic health estimates in aging populations.

PMID- 19388367
TI  - Medication use among senior Canadians.
AB  - Based on data from the 1996/1997 (institutional component) and 1998/1999
      (household component) National Population Health Survey, seniors were major
      consumers of prescription medications, over-the-counter (OTC) products, and
      natural and alternative medicines. Almost all (97%) seniors living in long-term
      health care institutions were current medication users (medication use in the two
      days before their interview), as were 76% of those living in private households.
      Over half (53%) of seniors in institutions and 13% of those in private households
      used multiple medications (currently taking five or more different medications).
      Both medication and multiple medication use were associated with morbidity.
      Medications for the nervous system, the alimentary tract and metabolism, and the
      cardiovascular system were reported most frequently. Among seniors in
      institutions, those with Alzheimer's disease were less likely to take multiple
      medication than were those without this condition.

PMID- 19388368
TI  - Evaluation of the coverage of linked Canadian Community Health Survey and
      hospital inpatient records.
AB  - BACKGROUND: Evaluation of the coverage that results from linking routinely
      collected administrative hospital data with survey data is an important
      preliminary to undertaking analyses based on the linked file. DATA AND METHODS:
      To evaluate the coverage of the linkage between data from cycle 1.1 of the
      Canadian Community Health Survey (CCHS) and inpatient hospital data (Health
      Person-Oriented Information or HPOI), the number of people admitted to hospital
      according to HPOI was compared with the weighted estimate for CCHS respondents
      who were successfully linked to HPOI. Differences between HPOI and the linked and
      weighted CCHS estimate indicated linkage failure and/or undercoverage. RESULTS:
      According to HPOI, from September 2000 through November 2001, 1,572,343 people
      (outside Quebec) aged 12 or older were hospitalized. Weighted estimates from the
      linked CCHS, adjusted for agreement to link and plausible health number, were
      7.7% lower. Coverage rates were similar for males and females. Provincial rates
      did not differ from those for the rest of Canada, although differences were
      apparent for the territories. Coverage rates were significantly lower among
      people aged 75 or older than among those aged 12 to 74.

PMID- 19388369
TI  - Combining cycles of the Canadian Community Health Survey.
AB  - BACKGROUND: A single cycle of the Canadian Community Health Survey (CCHS) may not
      meet researchers' analytical needs. This article presents methods of combining
      CCHS cycles and discusses issues to consider if these data are to be combined. An
      empirical example illustrates the proposed methods. DATA AND METHODS: Two methods
      can be used to combine CCHS cycles: the separate approach and the pooled
      approach. With the separate approach, estimates are calculated for each cycle
      separately and then combined. The pooled approach combines data at the micro-data
      level, and the resulting dataset is treated as if it is a sample from one
      population. RESULTS: For the separate approach, it is recommended that the simple
      average of the estimates be used. For the pooled approach, it is recommended that
      weights be scaled by a constant factor where a period estimate covering the time
      periods of the individual cycles can be created. The choice of method depends on
      the aim of the analysis and the availability of data. INTERPRETATION: Combining
      cycles should be considered only if the most current period estimates do not
      suffice. Both methods will obscure cycle-to-cycle trends and will not reveal
      changing behaviours related to public health initiatives.

PMID- 19388370
TI  - Complicating the story.

PMID- 19388371
TI  - Substituting authenticity for autonomy.

PMID- 19388372
TI  - Line, please.

PMID- 19388373
TI  - Line, please.

PMID- 19388374
TI  - Line, please.

PMID- 19388375
TI  - Line, please.

PMID- 19388376
TI  - True north.

PMID- 19388377
TI  - Government and science: the unitary executive versus freedom of scientific
      inquiry.

PMID- 19388378
TI  - Personal responsibility, public policy, and the economic stimulus plan.

PMID- 19388379
TI  - Case study. Waiting it out.

PMID- 19388380
TI  - Case study. Waiting it out. Commentary.

PMID- 19388381
TI  - Brain death: can it be resuscitated?

PMID- 19388382
TI  - The parental investment factor and the child's right to an open future.

PMID- 19388383
TI  - A planned death in the family.

PMID- 19388384
TI  - Choosing for another: beyond autonomy and best interests.
AB  - According to bioethics orthodoxy, when we ask, "What would the patient choose?"
      the patient's autonomy is at stake. In fact, what underpins the moral force of
      that question is a value different from either autonomy or best interests. This
      is the value of doing things in a way that is authentic to the person.

PMID- 19388385
TI  - Invitation to the dance: lessons from Susan Sontag's death.
AB  - The standard model for end-of-life decision-making gives roles to two parties-
      the physician, who explains the medical options, and the patient, who selects
      from among those options. The model can be harmful not only for individuals but
      also for the state, if the patient's right to control her own choices is
      understood as a positive right of access to whatever is available.

PMID- 19388386
TI  - A slippery preventive slope.

PMID- 19388387
TI  - Use of target-date funds in 401(k) plans, 2007.
AB  - WHAT THEY ARE: Target-date funds (also called "life-cycle" funds) are a type of
      mutual fund that automatically rebalances its asset allocation following a
      predetermined pattern over time. They typically rebalance to more conservative
      and income-producing assets as the participant's target date of retirement
      approaches. WHY THEY'RE IMPORTANT AND GROWING: Of the 401(k) plan participants in
      the EBRI/ICI 401(k) database who were found to be in plans that offeredtarget
      date funds, 37 percent had at least some fraction of their account in target-date
      funds in 2007. Target-date funds held about 7 percent of total assets in 401(k)
      plans and the use of these funds is expected to increase in the future. The
      Pension Protection Act of 2006 made it easier for plan sponsors to automatically
      enroll new workers in a 401(k) plan, and target-date funds were one of the types
      of approved funds specified for a "default" investment if the participant does
      not elect a choice. BRI/ICI 401(K) DATABASE: This study uses the unique richness
      of the data in the EBRI/ICI Participant-Directed Retirement Plan Data Collection
      Project, which has almost 22 million participants, to examine the choices and
      characteristics of participants whose plans offer target-date funds. EFFECT OF
      AGE, SALARY, JOB TENURE, AND ACCOUNT BALANCE: Younger workers are significantly
      more likely to invest in target-date funds than are older workers: Almost 44
      percent of participants under age 30 had assets in a target-date fund, compared
      with 27 percent of those 60 or older. Target-date funds appeal to those with
      lower incomes, little time on the job, and with few assets. On average, target
      date fund investors are about 2.5 years younger than those who do not invest in
      target-date funds, have about 3.5 years less tenure, make about $11,000 less in
      salary, have $25,000 less in their account, and are in smaller plans. EFFECT OF
      AUTOMATIC ENROLLMENT: While the EBRI/ICI database does not contain specific
      information on whether a 401(k) plan had automatic enrollment, this analysis was
      able to proxy for those who could be identified as automatically enrolled. The
      data show that workers who were considered to be automatically enrolled in their
      employer's 401(k) plan are significantly more likely to invest all their assets
      in a target-date fund than those who voluntarily joined, and were also less
      likely to have extreme all-or-nothing asset allocations to equities. EQUITY
      ALLOCATIONS AND FUND FAMILIES: One of the major questions surrounding target-date
      funds is the equity allocations that these funds use over time (the so-called
      "glide path") as a participant's retirement target date approaches. The glide
      paths of different target-date funds have significantly different shapes and
      starting/ending equity allocations. As of 2007, the equity allocation ranges from
      about 80-90 percent for 2040 funds (for workers about 30 years away from
      retirement), and from 26-66 percent for 2010 funds (for workers one year away
      from retirement)--a 40 percentage-point difference. Moreover, the fund families
      change their relative rank in equity allocation within the different fund years.
      This analysis finds that the relative rank of the equity allocation within a
      target-date fund does not appear to affect the percentage of participants
      investing all their account into that fund. Nevertheless, investors in specific
      fund families are more likely to invest all their assets in a single target-date
      fund from that family.

PMID- 19388388
TI  - Practice-based research comes of age.

PMID- 19388390
TI  - The learning practice: 1. The learning practice concept.
AB  - This first article of two explores the concept, benefits and stages in developing
      a learning practice, which is applicable to all branches of dentistry. The second
      article will consider building a learning practice. CLINICAL RELEVANCE:
      Developing a learning practice will ultimately be of value to patients.

PMID- 19388389
TI  - Direct posterior composites: a practical guide.
AB  - The restoration of posterior teeth with directly placed resin-bonded composite
      requires meticulous operative technique in order to ensure success. Case and
      material selection; cavity preparation; matrix selection; isolation; bonding;
      management of polymerization shrinkage; placement; finishing and curing of
      posterior composites--all present a series of challenges that dentists must
      master in order to ensure high-quality, long-lasting restorations. This paper
      describes and discusses these aspects of the provision of composites for
      loadbearing situations in posterior teeth. CLINICAL RELEVANCE: Successful
      restoration of posterior teeth with composite is an essential component of
      contemporary dental clinical practice.

PMID- 19388391
TI  - Autotransplantation of teeth: an overview.
AB  - Autotransplantation is the surgical repositioning of a tooth within the same
      patient. It can be thought of as a controlled avulsion and re-implantation of a
      tooth in a new, surgically prepared socket. The indications for its use are
      discussed, as too are factors affecting the success and the clinical procedures.
      The preservation and regeneration of the periodontal ligament is the key to
      success of this treatment. A case involving the transplantation of a premolar
      tooth into the central incisor location in a child is presented to show the
      different stages of the process. CLINICAL RELEVANCE: Autotransplantation is an
      underutilized technique which, when used within a multidisciplinary team, can
      offer an ideal treatment option for child or adolescent patients with missing or
      failing anterior teeth.

PMID- 19388393
TI  - An unerupted tooth?--who nose?
AB  - Foreign bodies may present to the general dental practitioner, either as a cause
      of complaint or, more commonly, as an incidental finding during routine
      examination. This article describes an unusual case where a rhinolith perforated
      the hard palate to appear in the mouth as an erupting tooth. CLINICAL RELEVANCE:
      It is useful for the general dental practitioner to be aware of the existence of
      foreign bodies, their sequelae and management.

PMID- 19388392
TI  - Treatment of traumatically intruded permanent incisor teeth: case report.
AB  - A case is presented of the management of traumatically intruded upper left
      central and lateral incisors. The intrusion of teeth involves damage to the
      gingival tissues, periodontal ligament, cementum, bone and the neurovascular
      supply to the pulp. There is a lack of evidence base concerning the ideal method
      of treatment of traumatically intruded permanent teeth in children. In this case,
      fixed orthodontic treatment was carried out, bringing the teeth into the correct
      occlusion, followed by endodontic treatment. CLINICAL RELEVANCE: In the treatment
      of intruded teeth, a combination of orthodontic and endodontic treatment can be
      utilized. The use of appropriate orthodontic mechanics and endodontic techniques
      may involve a multidisciplinary approach to achieve an acceptable result.

PMID- 19388394
TI  - Physical signs for the general dental practitioner. Case 62. Henoch-Schonlein
      purpura.

PMID- 19388395
TI  - Aspects of human disease. 30. HIV infection and AIDS.

PMID- 19388396
TI  - Final fatal blows.

PMID- 19388397
TI  - "New" York state of mind.

PMID- 19388398
TI  - Physician involvement in healthcare for the homeless.

PMID- 19388399
TI  - Introduction: Leaving the bedside.

PMID- 19388400
TI  - Taking the temperature of medicine: the data tells the story.

PMID- 19388401
TI  - A mountain of paper.

PMID- 19388402
TI  - Trading spaces: from wearing the lab coat to making the lab coat.

PMID- 19388403
TI  - Practicing politics and practicing medicine.

PMID- 19388404
TI  - Playing politics with the professional politicians: what is the doctor's role?

PMID- 19388405
TI  - Increasing student interest in family medicine and urban health care: the family
      care tract.
AB  - Throughout the last decade, general interest in primary care has drastically
      decreased. While medical students collectively show a high awareness for the
      significance of primary care during their first two years of medical school, this
      enthusiasm wanes for many as they complete their clinical years. As a result,
      fewer students enter into this concentration each year. In an attempt to mediate
      this changing interest, the University of Maryland School of Medicine Department
      of Family and Community Medicine has implemented the Family Care Track. This
      longitudinal experience spans the first two years of medical school and allows
      for mentorship by family medicine faculty, while also providing students with the
      opportunity to learn via the formation of long-term relationships with patients.

PMID- 19388406
TI  - The Governor's Task Force on Health Care Access and Reimbursement: a final
      report.

PMID- 19388407
TI  - [A crisis of values].

PMID- 19388408
TI  - [Apprenticeship for research in a school for midwifery: a quest for judgment of
      conscience].

PMID- 19388409
TI  - [Complexity of professional actions, qualitative research and evaluation,
      reliance and legitimacy. The case of research and formation of nurses].

PMID- 19388410
TI  - [Evaluation of professional practice--politics founded on quality].

PMID- 19388411
TI  - [Convincing results in medical research].

PMID- 19388412
TI  - [The process of integrating research in procedures of accreditation and practical
      professional evaluation].

PMID- 19388413
TI  - [The experience of uncertainty of fathers and mothers in the process of the
      announcement of cerebral palsy of their children].
AB  - This qualitative research shows differences and similarities between mother and
      father's experience of incertitude in the process of the announcement of the
      cerebral palsy and the adaptation strategies used. Interviews have been conducted
      with 17 parents (10 mothers and 7 fathers). Results of the research reveals three
      main triggering factors of incertitude: incertitude in regards with the survival
      of the child, the unpredictability of the evolution of the child and the
      ambiguity of the information regarding the cerebral palsy Triggering factors of
      the incertitude are the same for both parents but their reactions towards the
      these factors and their way of coping with the situation vary.

PMID- 19388414
TI  - [Evaluation of a preoperative virtual tour for parents and children].
AB  - A Canadian pediatric center has set a preoperative virtual tour on its website.
      This tour was evaluated by a descriptive study, in terms of utilization, efficacy
      and usefulness. The tour was utilized by 49.6% of the 123 families. Children of
      these families had a significant increase in knowledge from Time I (preop clinic)
      to Time 2 (day of surgery). Children and youth who did not use the tour reported
      themselves as more anxious the day of surgery but not significantly. There was no
      significant change in parents. The internet is a useful tool in families'
      preparation but cannot replace a direct interaction. Other researches are
      necessary in order to evaluate the impact of this type of preparation on the
      quality of care and on the child's recovery.

PMID- 19388415
TI  - [Chronic wound management in hospital care units--a literature review].
AB  - Chronic wounds are a major health problem, which nurses are dealing with daily.
      However, weak agreement exists with the dressing technique on chronic wounds. The
      practices described are often imprecise and even controversial. At least four
      procedures are depicted for this practice in Switzerland. This search of evidence
      is conduct on the dressing technique on chronic wounds in hospital care units.
      The debate on this issue is depicted and the terms of sterile and non sterile
      bandage are defined. The scientific and professional literature analyzed to
      determine the level of proof of the existing data does not state that one of both
      techniques--sterile versus non sterile--is more adequate than the other, for the
      chronic wounds management in hospital environment. The principles formulated on
      the basis of this literature review are therefore based on the experts' opinion.

PMID- 19388416
TI  - [Evaluation of professional practices: care of a child with maxillofacial
      palatine abnormalities and his family].

PMID- 19388417
TI  - [Discovery of domestic violence by nurses in a hospital setting: professional
      responsibility and enrichment in approaching the patient].

PMID- 19388418
TI  - [Nursing research at the service of nursing quality! Is it desirable and
      realizable?].

PMID- 19388419
TI  - [Nursing consultation in HIV-infected patients].

PMID- 19388420
TI  - The nursing workforce and global economic recession.

PMID- 19388421
TI  - Achieving workforce growth in UK nursing: policy options and implications.
AB  - OBJECTIVE: This paper examines how the National Health Service (NHS) in the UK
      achieved significant nursing workforce growth during the period between 2000 and
      2006 and discusses the policy implications of the methods used to achieve this
      staffing growth. METHODOLOGY: Data analysis, literature review and policy
      analysis. RESULTS: NHS nurse staffing growth was approximately 25% over the
      period 1997-2007, with most growth occurring in the years between 1999 and 2005.
      Whilst increases in intakes to home-based pre-registration education was a factor
      in achieving growth, the pace and level of growth which occurred was only
      possible by using active international recruitment, which was adopted as a
      deliberate national policy. The numbers of nurses and midwives entering the UK
      from other countries increased rapidly from 1999 onwards, to a peak in 2002, and
      then reduced markedly in the period from 2005 onwards. The policy of supporting
      international recruitment shifted rapidly in late 2005/2006 when financial
      difficulties hit the NHS and staffing growth was curtailed. DISCUSSION: Active
      international recruitment can contribute to health sector staffing growth,
      assuming the recruiting country has the resources to recruit and can tap into
      international markets, but it may not be effective in addressing all types of
      skills shortages. If it is not well linked to other components of workforce
      planning it may cause difficulties of over expansion, as well as raising broader
      issues of the ethics and impact.

PMID- 19388422
TI  - Staff satisfaction and retention and the role of the nursing unit manager.
AB  - Despite recent increases in nursing recruitment in Australia, participation in
      the workforce is still below the numbers predicted to meet future needs. This
      paper discusses factors impacting on nurses' job satisfaction, satisfaction with
      nursing and intention to leave in public sector hospitals in New South Wales
      (NSW), Australia. Staffing and patient data were collected on 80 medical and
      surgical units during 2004/5. This included a wide range of individual nurse data
      from a Nurse Survey; detailed and comprehensive staffing data including skill mix
      variables; patient characteristics; workload data; a profile of the ward's
      characteristics; and adverse event patient data. Nurses who were intending to
      remain in their job were more likely to be satisfied, be older, and have
      dependents. They were also likely to be experiencing good leadership and to have
      allied health support on the ward. Most nurses reported being satisfied with
      their profession, while a lower proportion reported satisfaction with their
      current position. Work environment factors such as nurses' autonomy, control over
      their practice and nursing leadership on the ward were statistically significant
      predictors of job satisfaction. This study will inform decision-making and policy
      for managers in both the public and private hospital sectors. This is the first
      large study which explored the work environment at the ward/unit level in public
      hospitals in NSW (Australia). It illustrates that there are no typical wards;
      each ward functions differently. The importance of nursing leadership at the ward
      level to job satisfaction, satisfaction with nursing and intention to leave,
      cannot be overstated.

PMID- 19388423
TI  - Human resources in nursing education: a worldwide crisis.
AB  - The global shortage of nurses is escalating. A key contributing factor to the
      production of new nurses is the growing shortage of qualified faculty. This paper
      explores the forces influencing the global faculty shortage, including those that
      increase demand and those that limit the supply of nursing faculty. The authors
      discuss potential solutions to the shortage, placing particular emphasis on
      leveraging the strengths of the profession to accelerate the progression of
      nurses to graduate school, the enhancement of funding for graduate education,
      changing the paradigm of clinical education, and the expansion of the science
      base for practice.

PMID- 19388424
TI  - The Australian nurse and midwifery workforce: issues, developments and the
      future.
AB  - The paper is concerned with data, concepts and analyses necessary for
      understanding the nurse and midwifery workforces at a macro-level, and for
      developing policies and plans that can best assure the quality and sufficiency of
      those workforces in the future. The size, composition and age profile of the
      nurse workforce are set out first. This is followed by an outline of the notions
      of 'attachment' to and 'separation' from a profession. Data on the population
      with professional nurse qualifications, whether working in the profession, in
      another occupation, or not working illustrates the patterns of 'attachment' and
      'separation' over the working age range. Historical developments since the 1960s
      are then considered, including the workforce size and age profile, the nurse
      labour market, pre-registration course completions, and movement in and out of
      Australian of nursing professionals. The nature and impact of the 'oversupply' of
      nurses in the early- to mid-1990s is discussed. Six matters are outlined that
      need to be taken into account when estimating future requirements. A discussion
      of the potential for quantitative impact on the overall nurse labour market from
      work redesign and role extension concludes that there is no easy solution for
      macro-level nurse workforce shortages, and that some otherwise very positive
      initiatives may exacerbate shortages. It is clear that further increases in pre
      registration (and pre-enrolment) intakes and completions will be necessary, as
      least for a further 8-12 years. Some of the barriers to such increases are noted
      and suggestions for the future made.

PMID- 19388425
TI  - Health reform: the human resource challenges for Central Asian Commonwealth of
      Independent States (CIS) countries.
AB  - This paper examines the key human resource issues for health amongst mid-level
      workers in Central Asia CIS countries. It focuses on Azerbaijan, Tajikistan and
      Uzbekistan highlighting the human resource issues that are evident within these
      countries and illustrating how they differ from those described in the sub
      Saharan developing countries. The key human resource issue highlighted by the
      World Health Organization Report [WHO. (2006). World Health Report: Working
      together for health. Geneva: WHO] was the scarcity of health workers. Four
      million health care workers were identified as essential if the health services
      of the world are able to meet current health needs. The primary area of need
      highlighted was in Africa. Africa bears the greatest burden of disease but has
      the lowest number of health care workers. In the CIS countries in Central Asia
      different human resource issues have emerged. The Soviet health care system was
      comprehensive but labour intensive it had a primarily acute and a specialist
      disease focused approach with little investment in primary and community health
      care. It was unsustainable and the legacy that it left the new Central Asian
      emerging nations was of a large workforce with poor levels of competence and
      outdated approaches to providing care along with a crumbling infrastructure. In
      response to this situation health reform has been introduced which focuses on a
      family model of primary health care with family doctors supported by Family
      Health Nurses. This approach is beginning to make a difference to the morbidity
      and mortality of the populations but still has a long way to go before its full
      benefits are realised.

PMID- 19388426
TI  - Scaling up the global nursing health workforce: contributions of an international
      organization.
AB  - In this paper key highlights of the scholarly work presented at the Toronto 2008
      Global Alliance for Nursing Education & Scholarship (GANES) conference are
      summarized, challenges opportunities and issues facing nursing education globally
      arising from the conference discourse are outlined and initial steps are
      suggested as a way forward to a shared global view of baccalaureate and graduate
      nursing education and scholarship. This shared view arises from beginning
      understandings of the issues and opportunities we face globally starting with and
      building upon the lessons learned from the literature and from the experiences of
      nursing educators and nursing education organization locally, regionally,
      nationally and internationally. The theme of the groundbreaking GANES Toronto
      conference was "Educating the future nursing and health workforce: A global
      challenge". One hundred seventy delegates from 17 countries attended the event,
      with over 80 papers presented. A primary focus of GANES is the contribution of a
      strategic alliance of national nursing education organizations to contribute to
      nursing education leading practices and policy that address the scaling up of
      global nursing and health workforce. The founding members of GANES see a clear
      link between a strong educational infrastructure and strong scholarship
      activities in nursing and the ability of a society to be healthy and prosperous.
      Evidence presented at the recent GANES conference supports that belief. Through
      the strength of partnerships and other capacity-building efforts, member
      countries can support each other to address the global nursing education and
      health challenges while respecting the local issues.

PMID- 19388427
TI  - Dental and alveolar arch asymmetries in normal occlusion and Class II Division 1
      and Class II subdivision malocclusions.
AB  - AIM: To compare the degree of intra- and interarch dentoalveolar asymmetry among
      patients with a normal occlusion, Class II Division 1 malocclusion, and Class II
      subdivision malocclusion. METHODS: The sample comprised dental casts of 150 (72
      males [ages 22. 1 +/- 3.11 and 78 females [ages 21.1 +/- 2.1]) normal occlusion
      subjects, 106 (45 males [ages 17.8 +/- 1.8] and 61 females [ages 16.5 +/- 2.91)
      Class II Division 1 patients, and 40 (18 males [ages 15.8 +/- 2.8] and 22 females
      [ages 15.2 +/- 3.3]) Class II subdivision malocclusions. Maxillary and mandibular
      reference lines were constructed and used for the intraarch asymmetry
      measurements. Thirty-six width measurements were performed on the dental casts of
      each subject. Analysis of variance (ANOVA) was used for comparisons of the
      groups, and Pearson's correlation coefficients were computed to determine the
      interarch associations. RESULTS: No statistically significant intra-arch
      asymmetry was found for maxillary and mandibular dental arch and alveolar width
      in any of the three groups. All variables were larger on the right side in the
      normal occlusion subjects. Further, the left side maxillary dental and alveolar
      arch width measurements were larger in the Class II Division 1 group. None of
      these differences, however, were statistically significant. In the Class II
      subdivision group, only the Class II sides' mandibular dental arch measurements
      were larger (P < .05). Maxillary and mandibular total dental arch and alveolar
      width dimensions differed among the groups (P < .001). Except for maxillary and
      mandibular canine alveolar width, opposing interarch dental and alveolar
      landmarks were significantly correlated with the transverse dimensions.
      CONCLUSION: Although some landmarks in the current study showed statistically
      significant and insignificant differences, the mean arithmetic differences were
      small, inconsistent, and not likely clinically important.

PMID- 19388428
TI  - Do alveolar bone defects merit orthodontists' respect?
AB  - AIM: To investigate the incidence and distribution of alveolar bony defects in
      the mandibular anterior area. METHODS: A flap procedure was performed to expose
      the labial alveolar bone of the mandibular anterior area of 32 patients. The
      presence of alveolar defects including dehiscences and fenestrations were
      recorded. RESULTS: Seventy-eight percent (25) of the examined patients had at
      least one tooth with an alveolar bony defect. Dehiscences were found to be most
      commonly associated with the midline of the labial surface of mandibular left and
      right canines followed by the mesiolabial line of the same teeth. CONCLUSIONS:
      The structure and topography of alveolar bone should be considered prior to the
      treatment planning and tooth movement. Moreover, there is a tremendous need to
      develop a noninvasive precise method for diagnosing alveolar defects.

PMID- 19388429
TI  - In vivo and in vitro study of the shear bond strength of brackets bonded to
      enamel using halogen or LED light.
AB  - AIM: To evaluate the shear bond strength in vivo and in vitro of metallic
      brackets bonded to human teeth with light-curing bonding material, using two
      types of light-curing units. METHODS: Sixty human premolars were divided into six
      groups. In the GI and GII groups, the brackets were directly bonded to
      volunteers' maxillary and mandibular second premolars on the right and left
      sides, respectively, of their mouths. In the other groups, the brackets were
      bonded to extracted first premolars. The polymerization was performed in GI,
      GIII, and GV with an LED (light-emitting diode) device, while in GII, GIV, and
      GVI, a halogen light was used. In GI and GII, shear strength tests were conducted
      using a portable digital dynamometer placed directly in the patients' mouths. The
      teeth from GIII, GIV, GV, and GVI were stored in distilled water at 37 degrees C
      for 24 hours. Afterward, they were thermocycled between 5 degrees and 55 degrees
      C. Then, in GIII and GIV, a Universal Testing Machine was used; in GV and GVI,
      mechanical tests were performed with a digital dynamometer. The bracket/adhesive
      failure modes were evaluated with the Adhesive Remnant Index (ARI). RESULTS: The
      average values of the shear strengths in MPa were: GI = 3.65; GII = 4.39; GIII =
      6.45; GIV = 7.11; GV = 4.67; and GVI = 4.21. CONCLUSIONS: The type of light
      curing unit did not interfere with the results of the mechanical tests in vivo or
      in vitro. The tests performed with a portable digital device obtained average
      values that were significantly lower than those performed with the Universal
      Testing Machine.

PMID- 19388430
TI  - Force-deflection properties of initial orthodontic archwires.
AB  - AIM: This in vitro study measured the force-deflection behavior of selected
      initial alignment archwires by conducting three-point bending tests under
      controlled conditions. The study tested four wire designs: multistranded
      stainless steel, conventional stainless steel, superelastic nickel-titanium, and
      thermoactivated nickel-titanium archwires. METHOD: The wires (n = 15) were
      ligated into stainless steel brackets with steel ligatures. A testing machine
      recorded deactivations at 2.0 mm of deflection at 37 degrees C. Force-deflection
      measurements were recorded from only deactivation. Forces on deactivation were
      compared by one-way analysis of variance (ANOVA) and Tukey post-hoc tests.
      RESULTS: Significant differences (P < .05) in deactivation forces were observed
      among the tested wires. The multistranded stainless steel wire had the lowest
      mean deactivation force (1.94 N), while the conventional stainless steel group
      had the highest value (4.70 N). The superelastic and thermoactivated Ni-Ti groups
      were similar to the multistranded wire (P > .05). CONCLUSION: Both nickel
      titanium and multistranded steel archwires tested are potentially adequate for
      use during the leveling and aligning phase of orthodontics.

PMID- 19388431
TI  - Complications of orthodontic treatment: are soft drinks a risk factor?
AB  - Soft drink consumption has steadily increased in recent decades in both western
      and developing countries. The trend is most apparent among children and
      adolescents. This rise in soft drink consumption has raised concerns among health
      care professionals, including dental practitioners. Accordingly, the effects of
      soft drinks on dental health have been investigated. Several studies have shown
      that dental problems, such as caries, enamel erosion, and corrosion of dental
      materials, may be associated with soft drink consumption. Because orthodontic
      appliances restrict toothbrush access, patients undergoing orthodontic treatment
      need special oral care and advice. This article reviews the risks and
      implications of soft drink consumption for orthodontic patients.

PMID- 19388432
TI  - A treatment method for Class II Division 1 patients with extraction of permanent
      maxillary first molars.
AB  - Throughout the years, various treatment modalities have been presented for the
      treatment of Class II Division 1 malocclusions. The goal of this paper is to
      present a treatment approach that involves the extraction of the maxillary first
      molars followed by use of fixed appliances with low-friction brackets. This
      treatment approach has proven to be an efficient treatment modality for Class II
      Division 1 malocclusions, especially with noncompliant patients.

PMID- 19388433
TI  - Mia-assisted orthodontic treatment for dental malocclusion secondary to
      periodontal disease.
AB  - In contemporary dental care, an increasing number of adult patients with
      periodontal disease are seeking orthodontic treatment. Achieving optimal results
      in such adult patients is difficult because decreased posterior tooth anchorage
      is risky. This case report demonstrates the use of miniscrew implant anchorage
      (MIA) in a Chinese male 21 years 5 months of age with maxillary and mandibular
      anterior dental spacing, bimaxillary protrusion, and severe bone loss caused by
      periodontal disease. Prior to orthodontic treatment, the patient underwent
      treatment to control his periodontitis. The patient was treated with 0.022-in
      straight-wire orthodontic appliances. After 17 months of active orthodontic
      treatment, the patient had healthier periodontal tissue with increased bone
      support, as well as improved facial esthetics and a functional occlusion. The
      results demonstrate that MIA is useful in enhancing anchorage in patients with
      bone loss associated with severe periodontal disease.

PMID- 19388434
TI  - Treatment of a patient with a severe Class III and open bite: a case report.
AB  - The Class III malocclusion with mandibular prognathism and open bite can be a
      result of excessive mandibular growth, underdevelopment of the maxilla,
      environmental factors, and trauma to the jaws. Correction of this malocclusion
      can involve an orthodontic or a combined orthodontic-orthognathic approach.
      Skeletal asymmetries can complicate this situation, making treatment more
      difficult. This skeletal Class III deformity with skeletal open bite case
      presentation involves treatment with a combined orthodontic-bimaxillary
      orthognathic approach following rhinoplasty. In addition, the patient's
      postoperative skeletal and dental stability was well-maintained after 1 year
      postoperation.

PMID- 19388435
TI  - Orthodontic treatment of cleft lip and alveolus using secondary autogenous
      cancellous bone grafting: a case report.
AB  - AIM: This paper concerns orthodontic alignment of the maxillary lateral incisor
      on the cleft side of a lip and alveolar cleft patient after a secondary
      autogenous cancellous bone graft at the late stage of mixed dentition. SUBJECT
      AND TREATMENT: The patient was a Japanese girl 9 years 7 months of age who
      presented at the authors' clinic with a repaired lip and alveolar cleft and an
      incisor crossbite. At 12 years of age, a secondary bone graft of the alveolar
      ridge was performed using bone harvested from the iliac crest. At 14 years 7
      months of age, a conventional fixed appliance was placed. RESULTS: The lateral
      incisor on the cleft side was brought to the line of occlusion by orthodontic
      alignment. A Class I molar relationship on both sides and a satisfactory facial
      profile were achieved. After a 2-year retention period, the occlusion and
      esthetics were maintained. Five years after grafting, however, a satisfactory
      bone level was not achieved due to positioning of the root of the lateral
      incisor, which was not completely upright in the bone graft area due to root
      tipping.

PMID- 19388436
TI  - VIP interview.

PMID- 19388438
TI  - Simplifying a complex restorative case.
AB  - This article has several purposes. First, it will show how a seemingly complex
      case can be broken down into simpler elements. Second, it will demonstrate how
      the temporary restorations we create serve as templates for the definitive
      restorations. Finally, and equally important, the third purpose of the article is
      to show how a person's dental apparatus has an impact on the quality of his/her
      life.

PMID- 19388437
TI  - Effect of occlusal conditions on neuromuscular function for a healthy population.
AB  - This study was designed to measure and describe the dynamic function of the
      muscles of mastication in healthy, dentate adults. Specifically, the study was
      designed to determine if there are common patterns of masticatory muscle function
      and whether a given occlusal loading model generates more muscle activity than
      another.

PMID- 19388439
TI  - Oral and maxillofacial pathology. Case of the month: cherubism.

PMID- 19388440
TI  - Financial advantages: misleading information in the credit card-processing
      industry.

PMID- 19388441
TI  - Is nursing escaping the recession?

PMID- 19388442
TI  - 10 tips for perfecting a nursing interview.

PMID- 19388443
TI  - Money fears--most nurses have a few . . . what's yours?

PMID- 19388444
TI  - The OTHER nursing shortage.

PMID- 19388445
TI  - [Health care can "conjure away" death, but not give consolation].

PMID- 19388446
TI  - [Check list reduces the risk of mix-ups and medical errors. When left is right,
      right is wrong].

PMID- 19388447
TI  - [Chickenpox not always a harmless child disease. General vaccination in Sweden
      can prevent significant morbidity].

PMID- 19388448
TI  - [Catheters often lef inserted for a long time. Point prevalence study in
      Skaraborg].

PMID- 19388449
TI  - [Brachial plexus injuries in adults. Early reconstruction for better clinical
      results].

PMID- 19388450
TI  - [Pitfalls in pain measurement. Visual analog scale as pain assessment method
      questioned].

PMID- 19388451
TI  - [Diverticulitis].

PMID- 19388452
TI  - [Long-term adverse effects of SSRI].

PMID- 19388453
TI  - [Doubled paracetamol dosage--wrong and dangerous].

PMID- 19388454
TI  - [Can neuropathic pain be handled in ten minutes?].

PMID- 19388455
TI  - [Good care requires several information services].

PMID- 19388456
TI  - [Calcium antagonists--how does Furberg see them now?].

PMID- 19388457
TI  - [Cultural disease and shortage of knowledge].

PMID- 19388458
TI  - [Aggression and mobbing among correctional officers].
AB  - BACKGROUND: The paper addresses the issue of violence among correctional
      officers. The aim of the study was to assess the frequency of exposure to
      violence in this professional group. MATERIALS AND METHODS: The study comprised
      the sample of 222 correctional officers who voluntary and anonymously fulfilled
      the MDM questionnaire. The MDM Questionnaire allows for assessing exposure to
      aggression and mobbing at work. RESULTS: Preliminary assessment of exposure to
      single aggressive acts and mobbing shows a quite alarming tendency--around one
      third of subjects under the study experienced repetitive aggressive acts from
      coworkers and/or superiors. CONCLUSIONS: The problem of organizational aggression
      in correctional institutions should be recognized in details to develop effective
      preventive measures against violent behaviors occurring at work.

PMID- 19388459
TI  - [Masculinity, femininity, androgyny and work stress].
AB  - BACKGROUND: It was assumed that good mental health is associated with the
      traditional bipolar model of masculinity-femininity i.e., gender-schematic men
      and women. Bem and Lenney questioned this assumption and revealed that
      androgynous individuals endorse both warm and forceful self-characteristics, so
      they perform well in situations where either variety of assertiveness is
      appropriate. Compared with sex-typed individuals, they are more competent, better
      adjusted psychologically with the better stress resistance. The question appears
      how androgynous individuals assess the stress at their workplace. Little research
      has been conducted on the effects of gender role orientations on occupational
      stress. MATERIALS AND METHODS: A group of 308 participants (123 females and 185
      males), employed in the municipal trasnportation enterprise, completed a battery
      of instruments dealing with gender (The Bem Sex Role Inventory by Kuczynska) and
      work stress (The Subjective Assessment of Work Questionnaire by Dudek et al.).
      RESULTS: Psychological gender is associated with the experienced work stress.
      Undifferentiated individuals, androgynous men and masculine women perceived their
      workplace as the most stressful. Work stress-generated factors were represented
      by physical conditions and roles performance. CONCLUSIONS: It is expected that
      the obtained results may be the source of important hints for the stress
      management in various types of organizations on various levels.

PMID- 19388460
TI  - [A quality assessment of prophylactic examinations carried out by physicians of
      various specializations and qualifications among employees in the Pomorskie
      Voivodeship in the years 2005-2008].
AB  - BACKGROUND: The quality assessment of the prophylactic examinations of employees
      in the context of professional qualifications of physicians, presented by the
      authors, distinguished four groups of physicians legally entitled to conduct
      these examinations: physicians specialized in occupational medicine or with
      equivalent specializations, general practitioners and those with a six-year
      experience in industrial health service. The aim of the study was to compare the
      quality of prophylactic examinations and procedural errors made by these four
      groups of physicians. MATERIALS AND METHODS: The protocols of inspections carried
      out by occupational medicine center in Gdansk in the years 2005-2008 were used
      for analysis. The criteria have been singled out on the basis of occupational
      health legal regulations. RESULTS: Significant differences were noted in the
      quality of the conducted prophylactic examinations. CONCLUSIONS: Occupational
      medicine specialists were found to be the only group of physicians sufficiently
      qualified to conduct prophylactic examinations. In view of the study results it
      seems necessary to modify the training system as well as to revise professional
      knowledge and qualifications especially among physicians without occupational
      medicine specialization or to verify the range of competences assigned to them in
      the field ofprophylactic examinations.

PMID- 19388461
TI  - [Efficiency of the patient's signature in examinations performed by the
      occupational medicine doctor].
AB  - BACKGROUND: A special relationship occurring between the doctor and the patient,
      besides many stipulations of the ethical nature, is controlled by numerous legal
      regulations. In the Polish legislative system, there are no clear and unequivocal
      regulations that would precisely define the diagnostic-therapeutic process.
      Communication, namely the exchange of information between the doctor and the
      patient plays a particular role in this process in which the doctor bears much
      greater responsibility than the patient, and thus is obliged to provide the
      patient with the comprehensible information presented in such a way that he or
      she would be able to interpret it properly. MATERIAL AND METHODS: The analysis
      comprised the binding legislation concerning prophylactic examination as well as
      drivers examination. The problem was discussed taking into account the current
      court judgments. RESULTS: The doctor should pay particular attention to adjusting
      the quality, quantity and way of conveying the information to the patient's
      ability to acquire and interpret it properly. This ability is associated with the
      patient's personal traits. There are no algorithms for the doctor-patient
      communication. The occupational medicine doctors are in a better situation as
      legislative regulations pertaining to specificity of their health services may
      indicate proper communication between the doctor and the patient. CONCLUSIONS:
      The importance of this communication has been notified in the legislative
      doctrine, where the idea of informative mistake has been formed. Such a mistake
      may have significant consequences especially for the occupational medicine
      doctors due to the specificity of performed functions. The article discusses
      legislative aspects concerning the exchange of information at the doctor-patient
      level, and presents some examples of judgments of Polish courts as well as
      numerous indications useful in everyday practice.

PMID- 19388462
TI  - [Occupational medicine physicians: acceptance of the professional role and
      motives for the choice of specialization].
AB  - BACKGROUND: The professional role of the physician embraces a relatively
      permanent and internally coherent system of behaviors perceived as the reaction
      of other people to expectations and actions related to health problems.
      Performing this role is the main source of income, social status and prestige. It
      should be stressed that the role of specialist in occupational medicine differs
      from that of specialists in other disciplines. Its distinctive feature is that it
      is not oriented towards treatment, but towards prevention. MATERIAL AND METHODS:
      The study was carried out in 2006, using a questionnaire mailed to a random
      sample of 820 specialists in occupational medicine or industrial medicine
      (response rate, 35%) and conducting free interviews with 15 experts. RESULTS: The
      positive response to the question whether he or she would choose again the
      specialization in occupational medicine was an indicator of the acceptance of the
      assumed professional role. The results of the survey showed that 76% of
      respondents were positive and only 19% would have chosen another specialization.
      The responses to this question were diversified by the socio-demographic factors.
      On the basis of this diversification two profiles were constructed, favorable and
      unfavorable for the acceptance of the choice made in the past. Lack of work
      satisfaction, poor opportunities for professional advancement, and limited
      financial profits were reported as the major reasons for choosing other
      specialization than occupational medicine. The most frequently reported motives
      for choosing specialization in occupational medicine were the need to meet the
      requirements of the occupied position, the interest in this branch of knowledge
      and professional skills. It was also indicated that the acceptance of the role
      performed by the occupational medicine physician was strongly associated with the
      above mentioned motives and the expected financial profits. CONCLUSIONS: The
      majority of specialists in occupational medicine are satisfied with the choice of
      their specialization. Their choice was mostly inspired by autotelic (interests)
      and instrumental (financial profits and meeting the job requirements) motives.

PMID- 19388463
TI  - [Outdoor work-related health hazards].
AB  - Selected health hazards of outdoor work are reported. The hazards are
      attributable to physical agents (cold and hot microclimate, UV radiation),
      chemical agents (e.g., pesticides and herbicides, exhaust fumes), fine
      particulate dust, biological agents (insect bites, organic dusts, bacteria,
      poisonous vegetables), excessive physical (static and dynamic) loads. Exposures
      to those agents may cause circulatory diseases (arterial hypertension, ischemic
      heart disease), symptoms of lower and upper spine or renal calculosis. Particular
      attention was paid to dermal diseases caused by exposure to solar radiation, such
      as sunburns, idiopathic dermatoses, chronic lesions, exacerbation of other skin
      diseases (lupus erythematosus, porphyria), phototoxic and photoallergic
      reactions, melanoma and nonmelanoma skin cancer. Besides, solar radiation causes
      premature skin ageing and premalignant lesions (lentigo maligna, solar keatosis).

PMID- 19388464
TI  - [Electromagnetic fields emitted in radio- and microwave- frequency range:
      equipment and methods for the environment protection and survey measurements].
AB  - In the paper a review of electromagnetic field sources in radio- and microwave-
      frequency range is presented. The aim of the study was to analyze possibilities
      and methods used to survey electromagnetic field (EMF) measurements. Selective
      and broadband methods with examples of apparatus are described. The accuracy of
      typical EMF survey measurements was estimated.

PMID- 19388465
TI  - [Bioelectromagnetic studies: an analysis of errors in evaluation of
      electromagnetic field exposure].
AB  - This paper presents a review of exposure systems used in biomedical studies.
      Typical exposure systems of the whole frequency range are described. The
      attention was paid to technical limitations of applicability of the discussed
      exposure systems and the problem of correlation between the study results
      obtained in closed (TEM cell) and free spaces. Computer simulations of power
      absorbed by investigated objects with different numerical methods were made. As
      presented estimations show, electromagnetic energy absorption may differ between
      individual objects. The difference is a function of the system dimension and the
      number of exposed objects. Moreover, the energy distribution in a single object
      is a function of the frequency, system dimension, and placement of the object in
      relation to field vectors, not mentioning individual properties of the object.
      The presented results undermine the interpretation of the results of biomedical
      investigations carried out with use of closed exposure systems. Even if all
      inaccuracies and approximations in presented estimations are taken into account,
      the significance of mutual interactions between tested objects and exposure
      systems raises no doubts. Therefore, an attempt should be made to re-interpret
      the results of biomedical studies and to develop a closer cooperation between
      physicians and engineers.

PMID- 19388466
TI  - Transcranial sonography in the evaluation of pineal lesions: two-year follow up
      study.
AB  - We have recently reported that transcranial sonography (TCS) is a method
      competitive to magnetic resonance neuroimaging (MRI) in the evaluation of pineal
      gland lesions. The aim of the present is study was to assess the usefulness of
      TCS in a larger patient sample during a two-year follow up. Twenty patients with
      incidental pineal gland cyst (PGC) detected by MRI scan of the brain and 40
      healthy controls without any previous documented data on a disease related to
      pineal gland were evaluated by TCS and compared with MRI scans. There were no
      statistically significant differences in PGC size measured by TCS by two
      observers (p = 0.475), PGC size measured by TCS and MRI (first observer, p =
      0.453; and second observer, p = 0.425), size of the pineal gland measured by TCS
      and MRI in control group (first observer, p = 0.497; and second observer, p =
      0.370), and pineal gland size measured by TCS by two observers in control group
      (p = 0.473). Study results suggested TCS to be a suitable method in the
      evaluation of pineal gland lesions. Although its resolution cannot match the MRI
      resolution, its repeatability and accuracy might add to its practical value. We
      suggest that the repeat MRI scan of such lesions might be replaced by clinical
      and TCS follow up.

PMID- 19388467
TI  - Correlation between anxiety, depression and burning mouth syndrome.
AB  - The aim of the study was to determine the level of anxiety and depression in
      patients with and without burning mouth syndrome, and to assess the possible
      association between the intensity of burning mouth and incidence of depression
      and anxiety. The study was conducted in a sample of 120 randomly chosen adult
      patients from two dentist offices in Nova Gradiska (Croatia). Patient data were
      collected by use of a questionnaire that consisted of four parts: history
      questionnaire, Beck's anxiety inventory (BAI), Zung's self-evaluation scale for
      rating depression, and visual analogue scale (VAS) for estimating the intensity
      of burning mouth syndrome. The presence of the symptoms of burning mouth syndrome
      was recorded in 35% of 120 subjects. A statistically more significant mean level
      of depression and anxiety was detected in the group of subjects with the symptoms
      of burning mouth syndrome. The association between the burning mouth syndrome,
      anxiety and depression was tested by Pearson correlation. The levels of burning
      mouth syndrome, anxiety and depression in subjects showed positive correlation.
      Study results indicated the level of anxiety and the level of depression to be
      higher in the group of subjects with the burning mouth syndrome. The intensity of
      the symptoms of anxiety and depression also was in positive correlation with the
      intensity of the burning mouth syndrome. This clearly points to the role of
      psychogenic factors, anxiety and depression in the etiology of the burning mouth
      syndrome, which should be taken in consideration when treating patients with the
      burning mouth syndrome.

PMID- 19388468
TI  - Multifocal intraocular "mix and match" lenses.
AB  - The new generation multifocal lenses provide the surgeon with several options to
      meet the specific visual needs and desires of patients. A revolution in
      presbyopia surgery is being driven by two multifocal intraocular lenses, ReStor
      and ReZoom. Combined implantation of the ReZoom multifocal lens in nondominant
      eye and ReStor multifocal lens in dominant eye has been demonstrated to produce
      statistically and clinically superior results in bilateral uncorrected
      intermediate vision improving vision effectiveness in presbyopia patients after
      cataract surgery. Also, the mix and match approach can maximize patient vision at
      both near and far distance, thus improving the patient quality of life.

PMID- 19388470
TI  - The first seven years of implantation of permanent cardiac pacemakers in a small
      urban community in central Croatia.
AB  - The aim of the study was to assess the situation with implantation of cardiac
      pacemakers and to critically evaluate the possibility of this method of
      treatment. The study was conducted from 2001 to 2007. Data on a total of 211
      operations were included in the study. There were 121 (57.3%) male patients, mean
      age 69.7 years, and 90 (42.7%) female patients, mean age 74.5 years. Total number
      of operations increased from 18 in 2001 to 24 in 2002, 28 in 2003, 38 in 2004, 38
      in 2005, 30 in 2006 and 35 in 2007. Primo implantation was carried out in 196
      (92.9%) cases. The following types of pacemakers were used: VVI in 79 (40.3%),
      VVIR in 73 (37.2%), DDD in 7 (3.6%), DDDR in 18 (9.2%), VDD in 17 (8.7%) and AAIR
      in 2 (1.0%) cases. ECG indication was second degree heart block in 40, third
      degree heart block in 86, chronic atrial fibrillation with bradyarrhythmia in 57,
      sick sinus syndrome in 27 cases and trifascicular block in one case. The symptoms
      included dizziness in 126, syncope in 52, dyspnea in 45, bradycardia in 12, chest
      pain in 3 and cerebral dysfunction in 2 cases. In conclusion, our patients now
      receive appropriate treatment within a shorter time, thus reducing pressure upon
      large cardiac surgery centers. However, efforts should be continuously invested
      in approaching European standards of artificial pacemaker implantation.

PMID- 19388469
TI  - Correlation of serum S100B concentration with hospital stay in patients
      undergoing CABG.
AB  - S100B protein has been proposed to be a serum marker of cerebral injury in
      patients undergoing cardiac surgery. The question to be answered in the present
      study was whether an increase in serum S100B concentration after the surgery
      correlated with the length of hospital stay in patients undergoing coronary
      artery bypass grafting. To answer this question we measured serum S100B
      concentration preoperatively, at the end of the operation, and on day 1 and day 5
      of the surgery in 32 patients undergoing coronary artery bypass grafting. The
      median (min; max) hospital stay was 7 days (5; 34), and serum S100B concentration
      was 0.075 mg/L (0.050;0. 095) preoperatively, 0.840 mg/L (0.390; 1.500)
      immediately after the operation, 0.180 mg/L (0.150;0. 280) on day 1 and 0.100
      mg/L (0.080;0. 120) on day 5 of the operation. None of the patients had clinical
      signs of cerebral injury. Multivariate linear regression analysis indicated serum
      S100B concentration on day 1 (p = 0.0296) and day 5 (p = 0.0021) of the operation
      to correlate with the length of hospital stay independently of the type of
      operation (with or without the use of cardiopulmonary bypass) and patient
      clinical characteristics. Our data suggest that serum S100B concentration on day
      1 and day 5 of the operation may have prognostic value in patients without
      clinical signs of cerebral injury. However, this pilot study should be extended
      to a larger group of patients to confirm this observation.

PMID- 19388471
TI  - An individualized approach in the education of asthmatic children.
AB  - Asthma is the most prevalent chronic disorder of childhood. In a large number of
      cases, it can be well managed. In addition to accurate diagnosis, appropriate
      therapy and control of environmental factors, a good educational program is
      required, which has not yet received due attention. Prompted by the fact that a
      large number of asthmatic children and their parents lack sufficient knowledge
      about asthma, six years ago we launched an individual educational program for all
      asthmatic children over seven years of age and their parents. We monitored a
      group of 58 asthmatics, the first to have completed our individual educational
      program, during the year before and the year after they had received individual
      education. The prerequisites for inclusion in the study were that the child was
      over seven years of age, diagnosed with chronic asthma according to the GINA
      guidelines and had been monitored for one year prior to receiving individual
      education. We compared the number of asthma exacerbations, hospitalizations due
      to asthma, days with asthmatic symptoms, the mean value of the forced expiratory
      volume in 1 second (FEV 1), and the mean dose of inhaled corticosteroids (ICS)
      taken during the year before and the year after receiving individual education.
      Study results showed the number of asthma exacerbations (p < 0.0001),
      hospitalizations due to asthma (p = 0.0236) and days with asthmatic symptoms (p <
      0.0001) to have significantly reduced, along with a significant increase in FEV 1
      (p < 0.0001) and lower mean ICS dose (p < 0.0001) upon completion of individual
      educational program. It is concluded that the addition of individual education in
      the treatment of asthmatic children enables better control of the disease (lower
      number of hospitalizations and asthma exacerbations, increased FEV 1) with a
      lower mean ICS dose. The knowledge about asthma acquired by the children and
      their parents, self-management, compliance with the written asthma management
      plan, control of environmental factors, along with good cooperation of the
      patients and parents in the management of asthma certainly contributed to this
      favorable observation.

PMID- 19388473
TI  - Single incision laparoscopic surgery (SILS) cholecystectomy: where are we?
AB  - Laparoscopic cholecystectomy has become gold standard for cholecystectomy. The
      tendency of minimizing surgical trauma encourages the use of new approaches in
      laparoscopic surgery. Single incision laparoscopic surgery (SILS) cholecystectomy
      was first performed ten years ago; however, it is only recent technologic
      development that has enabled its wider acceptance. We report on a case of a 69
      year-old female patient scheduled for elective laparoscopic cholecystectomy due
      to symptomatic ultrasonography verified cholelithiasis. A single 2.5-cm long
      semicircular supraumbilical skin incision was used. Pneumoperitoneum was
      established with the Veress access needle. Abdominal cavity was entered through
      three trocars: 10-mm trocar for camera and two 5-mm trocars, each placed 1 cm
      laterally and cranially from the 10-mm trocar. Antegrade cholecystectomy was
      performed without stay suture placement. Postoperative course was uneventful. The
      benefits of transition from standard laparoscopic approach to SILS will not be as
      obvious as was the transition from open to laparoscopic cholecystectomy. However,
      it cannot be overstated that every additional incision and trocar placement poses
      a risk of bleeding, organ damage and incisional hernia. SILS approach is feasible
      with standard and slightly modified instruments for standard laparoscopic
      cholecystectomy, thus posing minimal additional challenge to the laparoscopic
      surgeon. Accordingly, we believe that the use of this approach for
      cholecystectomy is worthwhile.

PMID- 19388472
TI  - Combined megaloblastic and immunohemolytic anemia associated--a case report.
AB  - A 55-year-old female with a history of psychosis and rheumatoid arthritis was
      admitted to the hospital for fatigue and dizziness. At admission, macrocytic
      anemia, high serum lactic acid dehydrogenase (LDH) and gastrin concentrations,
      decreased serum vitamin B12 concentration, with macroovalocytes and poikilocytes
      in peripheral blood smear suggested the diagnosis of pernicious anemia. Indirect
      antiglobulin test (IAT) was negative. Surprisingly, treatment by vitamin B12 and
      folic acid administered for two weeks was ineffective and followed by transitory
      worsening of hemoglobin concentration on day 8. Repeat direct antiglobulin test
      (DAT) and IAT were positive. This immunotransfusion conversion, suggesting the
      presence of autoimmune hemolytic anemia, could be explained by change in the
      macroblastic erythrocyte population, i.e. emerging red cells with completely
      exposed membrane antigens due to vitamin B12 treatment and/or higher degree of
      dysregulation of the lymphocyte clone secreting erythrocyte autoantibodies. We
      proposed the coexistence of pernicious and autoimmune hemolytic anemia;
      therefore, methylprednisolone was added to vitamin B12 treatment. This therapy
      successfully improved hemoglobin and erythrocyte concentration. Although
      megaloblastic-pernicious anemia is a common disease, association of pernicious
      and autoimmune hemolytic anemia with two mechanisms of hemolysis (ineffective
      erythropoiesis and immune mechanism) is a rare condition, with only several
      dozens of cases described so far.

PMID- 19388475
TI  - Neck pain symposium, Sestre milosrdnice University Hospital, Zagreb, Croatia
      October 2, 2008.

PMID- 19388474
TI  - First case of single incision laparoscopic surgery for totally extraperitoneal
      inguinal hernia repair.
AB  - Laparoscopic approach to inguinal hernia repair is indicated for recurrent and
      bilateral hernias or as patient choice in unilateral primary hernias. Totally
      extraperitoneal (TEP) approach has some advantages over transabdominal
      preperitoneal (TAPP) approach, but has proved to be more technically demanding.
      It cannot be emphasized enough that every incision and trocar placement poses a
      risk of bleeding, organ damage, incisional hernia and less favorable cosmetic
      effect. Single incision laparoscopic (SILS) TEP hernia repair has reduced the
      number of incisions to minimum. A 60-year-old male patient presented with
      unilateral right sided primary indirect inguinal hernia. Laparoscopic SILS TEP
      repair was performed: a single 2.5-cm infraumbilical incision was made, the
      anterior rectus sheath was incised and a balloon dissection device was inserted
      over the posterior rectus sheath, guided to the pubic symphysis and inflated,
      resulting in separation of the peritoneum from the rectus muscle. This creation
      of the extraperitoneal space allowed for laparoscopic dissection to take place.
      We used a 10-mm optical trocar and two 5-mm trocars placed 1 cm laterally from
      the optical port. The operation was free from complications and the operative
      time was 90 minutes. Postoperative recovery was uneventful. We report on, to our
      knowledge, the first case of SILS TEP hernia repair. Based on this experience, we
      believe that SILS TEP is feasible. Adjacent placement of trocars in SILS reduces
      triangulation which, along with frequent crossing of instruments, renders this
      approach more demanding. Cosmetic benefit is clear; however, it remains to
      evaluate patient recovery, postoperative pain and complications in comparison to
      standard TEP.

PMID- 19388476
TI  - [Blood biochemical parameters of C-reactive protein and C-terminal telopeptides
      in adolescents and young people for early diagnosis of inflammatory diseases of
      the periodontium].
AB  - Fifty-one adolescents aged 15 to 16 years and 43 young persons aged 21 to 32
      years from risk and control groups were examined, their blood samples were tested
      for C-reactive protein (CRP) and C-terminal telopeptides (CTTP), by using
      immunoassay. Elevated CRP concentrations were found in risk-group adolescents and
      young persons as compared with healthy and comparison individuals, which
      suggested the development of an inflammatory process. The patients from these
      groups were observed to have increased CTTP. Thus, laboratory tests may be used
      for early diagnosis of inflammatory diseases of the periodontium.

PMID- 19388477
TI  - [Clinical significance of the determination of blood lactate in perinatology].
AB  - The paper substantiated the clinical diagnostic significance of lactate tests in
      various abnormalities. It presents the results of the past 25 years' research and
      practical studies of blood lactic acid in pregnant women and neonatal infants.
      More than 1000 pregnant women and 200 neonates were examined. The established
      peripheral blood lactate standards for pregnant women and the newborn and the
      values of lactic acid in varying hypoxia are given. It is concluded that lactate
      tests are of diagnostic value in perinatology.

PMID- 19388478
TI  - [Peripheral blood parameters in lipid metabolic disturbances in Far North
      migrants].
AB  - The authors present the results of a study of peripheral blood in Far North
      newcomers with lipid metabolic disturbances. All the dwellers having lipid
      metabolic disturbances are shown to have elevated counts of white blood cells,
      with the greatest changes occurring in the levels of blood corpuscles in subjects
      with hypertriglyceridemia.

PMID- 19388479
TI  - [D antigen varieties and determination of Rhesus factor].

PMID- 19388480
TI  - [Immunochemical characteristics of the autoagglutination factor of plague
      pathogen].
AB  - Immunochemical studies were performed to characterize the autoagglutination
      factor (AF) isolated from the plasmid-free variant of Yersinia pestis EV76
      strains. The preparation based on the capsule Cafl antigen isolated from the
      triplasmid variant of the same strain was used for comparison. AF and Cafl are
      the surface protein antigens of the plague pathogen, which are similar in their
      capacity for self-aggregation and in the molecular mass of a subunit (about 17
      kDa). However, unlike Cafl, FA gives rise to protein aggregates resistant to 2
      mercaptoethanol and sodium dodecyl sulfate. FA and Cafl were shown to be
      immunochemically different antigens, the antibodies to which were present in the
      plague hyperimmune equine serum. Thus, the new surface antigen of the plague
      causative organism, which induces the generation of antibodies during
      immunization with live bacteria of the vaccine Y. pestis strain, has been
      discovered.

PMID- 19388481
TI  - [Thyroid-stimulating hormone receptor antibodies in the diagnosis of Graves'
      disease in children].
AB  - The informative value of a method for determining total antibodies (Ab) to
      thyroid-stimulating hormone receptor (TSHR) in the diagnosis of Graves' disease
      was evaluated in 80 children with various causes of hyperthyroidism. With a RSHR
      Ab of > 1.6 IU/l, the diagnostic sensitivity and specificity of the test were
      100%. Patients with hyperthyroidism and no RSHR Ab require no active therapeutic
      intervention and need to be followed up.

PMID- 19388482
TI  - [The cytokine profile in patients with bacterial quinsy].
AB  - The state of the proinflammatory cytokines tumor necrosis factor-alpha,
      interleukin (IL)-1 beta, and IL-6, and the anti-inflammatory cytokine IL-10 was
      studied in patients with bacterial quinsy over time. There were significant and
      heterodirectional changes in the plasma level of proinflammatory and anti
      inflammatory cytokines with the normalization of their content in the period of
      late convalescence. The regular shifts of proinflammatory cytokines in patients
      with quinsy depended on the period and clinical forms of the disease, its
      severity, complications, comorbidity, and the plenitude of recovery. The paper
      discusses a role and implication of cytokines.

PMID- 19388483
TI  - [The cytokine profile in patients with acute viral hepatitis B and C].
AB  - The plasma levels of interleukin (IL)-1 beta, and IL-6, and IL-10 were studied in
      46 patients with acute viral hepatitis B and in 18 patients with acute viral
      hepatitis C at the peak of the disease during early and late convalescence. There
      was a significant increase in the levels of IL-1 beta and IL-6 and a reduction in
      the concentrations of IL-10, which was most evident at the peak of the disease in
      patients with acute viral hepatitis C as compared with those with hepatitis B.

PMID- 19388484
TI  - [Diagnostic value of seminal bactericidal activity in bacteria carriers].
AB  - Seminal bactericidal activity (SBA) that is referred to as a factor of natural
      resistance and that controls bacterial survival in the male urogenital tract is
      an integral index of the congenital adaptive mechanisms of mucosal defense. The
      paper shows changes in SBA and other indices of the functional activity of the
      reproductive tract in male patients with different forms of bacteria carriage.

PMID- 19388485
TI  - "Unnatural deaths," criminal sanctions, and medical quality improvement in Japan.

PMID- 19388487
TI  - "Till naught but ash is left to see": statewide smoking bans, ballot initiatives,
      and the public sphere.

PMID- 19388486
TI  - Opening stem cell research and development: a policy proposal for the management
      of data, intellectual property, and ethics.

PMID- 19388488
TI  - A national survey of medical error reporting laws.

PMID- 19388490
TI  - Home blood pressure monitoring: its potential in primary health care.

PMID- 19388491
TI  - I-123-MIBG cardiac uptake imaging, in familial dilated cardiomyopathy.
AB  - The pathological significance of myocardial adrenergic activity in patients with
      heart failure is well documented. No previous study has assessed the usefulness
      of I123-metaiodobenzylguanidine (123I-MIBG) cardiac uptake imaging for the
      evaluation of familial dilated cardiomyopathy (DCM). OBJECTIVE: To evaluate
      cardiac adrenergic activity, using 123I-MIBG cardiac uptake imaging, in members
      of a genotyped family with DCM. METHODS: Clinical evaluation, 12-lead ECG, 2D
      echocardiogram, heart rate variability analysis by 24h Holter, plasma B-type
      natriuretic peptide (BNP) measurements and 123I-MIBG cardiac imaging were
      performed in all participants. Anterior projection planar images and single
      photon emission computed tomographies of the thorax were obtained 20 min and 4
      hours after the intravenous administration of 370 MBq of 123I-MIBG (early and
      late images). Heart/mediastinal (H/M) ratio and myocardial washout (MW) rate were
      obtained based on the anterior planar images. In polar maps, segmental uptake of
      123I-MIBG was evaluated using a 4-grade visual score: grade 1 - uptake > 75% of
      maximum myocardial uptake (MMU); grade 2 - uptake 51-75% of MMU; grade 3 - uptake
      26-50% of MMU; grade 4 - uptake < or = 25% of MMU. RESULTS: Eleven adults were
      included: 4 with DCM, 4 with isolated left ventricular enlargement (LVE), and 3
      with normal echocardiogram. Patients with DCM and LVE presented higher MW rates,
      lower H/M ratios and higher visual score grades than those with normal 2D
      echocardiograms. One patient with a normal echocardiogram but carrying the
      disease locus also presented an abnormal MIBG cardiac scintigram. CONCLUSION:
      Patients with the phenotypic expression of the disease (DCM and LVE) and even
      carriers of the DCM gene with normal echocardiograms may present an abnormal MIBG
      cardiac scintigram, probably reflecting cardiac adrenergic hyperactivity. If
      confirmed in larger numbers, this method may be useful for the evaluation of DCM
      families.

PMID- 19388489
TI  - Self-measurement of blood pressure in arterial hypertension--preliminary results
      from the AMPA study.
AB  - INTRODUCTION: The clinical usefulness of home blood pressure monitoring (HBPM) is
      still uncertain, and is currently a major topic of scientific debate. Some
      studies have stressed its potential role in the clinical decision-making process,
      but there have been few prospective studies addressing this subject. The AMPA
      study is intended to contribute to this debate, exploring the potential
      usefulness of this methodology in the clinical setting of arterial hypertension
      using a prospective, observational and multicenter design. METHODS: The study
      included 685 hypertensive patients (346 female), with a mean age of 54.2 +/- 11.1
      years (range: 17-86 years). All patients were being followed in primary care
      centers by their family doctors, and were being treated for arterial hypertension
      and other comorbidities. Forty-seven patients were smokers (6%), 90 (13%) had a
      personal history of cardiovascular disease, 42 (6%) were diabetic, 255 (37%) had
      dyslipidemia, and 31 (5%) were both diabetic and dyslipidemic. Blood pressure
      (BP) was measured in the brachial artery with a validated automatic blood
      pressure measurement device (Colson MAM BP 3AA1-2; Colson, Paris). This device
      has solid state memory (sufficient for 60 measurements) and an adaptable printer.
      A cuff appropriate for the arm size of each patient was used. All patients were
      instructed on how to operate the device correctly and how to perform the
      measurements in compliance with the study protocol. BP was always measured after
      a 5-minute resting period in a seated position. The protocol consisted of an HBP
      program over a period of five working days. Each day the patient performed six BP
      measurements in two different periods: three in the morning (between 6 and 10 am)
      and three in the evening (between 6 and 10 pm). Other clinical and anthropometric
      data were also collected. The HBP reference values adopted were 135 mmHg for
      systolic and 85 mmHg for diastolic BP. RESULTS: Analysis of BP behavior over time
      demonstrated a significant white-coat effect, with regression to the mean of BP
      levels after the first day of the HBP program. As a consequence, the first day
      values were excluded in determining mean HBP. This behavior was independent of
      gender, and was more pronounced in diabetic patients. Analysis of diagnostic
      concordance between office BP and HBP showed discrepancies in 27.4% of the
      patients. This prompted a change in diagnosis based on HBP values, with 133
      patients (19.4%) presenting uncontrolled office BP levels but normal HBP values,
      while 55 patients (8%) had elevated HBP in contrast to normal office BP.
      CONCLUSIONS: These first results of the AMPA study illustrate the superiority of
      HBP compared with office BP in the evaluation of hypertensive patients. HBP
      provides a better characterization of each patient's BP profile, and hence may
      help improve therapeutic and clinical decisions. Confirmation of the potential of
      HBP monitoring will be addressed in a prospective analysis (6-year follow-up) of
      the AMPA study in the near future.

PMID- 19388492
TI  - Influence of dyslipidemia and smoking on redox markers in humans--a critical
      study.
AB  - Experimental research indicates that oxidative processes play a role in
      susceptibility to a large number of diseases. A better understanding of the
      parameters affecting redox balance could delay and even prevent such processes.
      OBJECTIVE: The present study aims to investigate blood parameters associated with
      antioxidant systems in a Portuguese population for the first time, taking into
      consideration gender, age range, lipid profile and smoking habits as influencing
      factors. DESIGN AND PARTICIPANTS: One hundred and eighty-three healthy Portuguese
      subjects of both genders were recruited from the metropolitan area of Lisbon. The
      group consisted of individuals aged from 20 to 70 years, who gave their informed
      consent before participating in the study. All subjects were screened to
      determine eligibility, which was based on a clinical report. Subjects were
      considered eligible if they had no acute or chronic illness and were not taking
      any drugs or dietary supplements that could compromise the values of the studied
      parameters. The subjects were then divided into different subgroups according to
      gender, age range, lipid profile and smoking habits. METHODS: Whole blood
      glutathione peroxidase activity and serum albumin, transferrin and uric acid were
      determined using commercially available kits. Superoxide dismutase activity in
      erythrocytes and thiobarbituric acid reactive substances in serum were measured
      using methods published elsewhere. RESULTS: Glutathione peroxidase activity was
      not affected by any of the studied variables, but superoxide dismutase activity
      decreased with smoking. Albumin levels remained unchanged under all conditions.
      Hyperlipidemia was associated with higher lipid peroxidation as well as higher
      uric acid levels. Gender was the strongest predictor for transferrin, total iron
      binding capacity and uric acid variations. Finally, a multivariate statistical
      model clearly separated genders and lipid profile and genders and smoking.
      CONCLUSIONS: The present study suggests that hyperlipidemia and smoking should be
      considered important selection criteria in epidemiological studies focusing on
      oxidative stress and on the atherosclerotic process.

PMID- 19388493
TI  - Optimization of blood glucose control in MI patients: state of the art and a
      proposed protocol for intensive insulin therapy.
AB  - Hyperglycemia in the acute phase of myocardial infarction (MI) is a marker of
      worse short- and long-term prognosis, in both diabetic and non-diabetic patients.
      Aggressive control of glycemia is recognized in the literature as an important
      therapeutic target, being associated with a better clinical outcome in this
      subset of patients. This means that a new approach should be adopted in patients
      admitted to coronary care units due to MI, control of glucose metabolism being
      pivotal in this context. Administering a continuous i.v. insulin infusion at a
      variable rate is acknowledged to be the best way to achieve rapid and sustained
      optimized metabolic control. The authors present an original protocol for
      intensive insulin therapy to be used in coronary care units, in both diabetic and
      nondiabetic patients admitted due to MI and with admission blood glucose of over
      180 mg/dl.

PMID- 19388494
TI  - The pathophysiology of heart failure with preserved ejection fraction and its
      therapeutic implications.
AB  - Heart failure with preserved ejection fraction (HFPEF) is a common syndrome,
      accounting for nearly one half of all heart failure patients. It mostly affects
      the elderly, usually with multiple comorbidities, and has a poor prognosis, with
      high mortality rates and a significant impact on quality of life. Nevertheless,
      evidence-based therapeutic strategies for the management of HFPEF are still
      lacking, and so treatment remains largely empirical. This is probably why current
      treatment of HFPEF has not led to a significant improvement in prognosis. In this
      review article we will discuss the pathophysiology of HFPEF and its implications
      for the best treatment strategies to apply in these patients. We will also review
      the evidence supporting the use of each therapy in HFPEF. In addition, we will
      consider how an understanding of the pathophysiology of HFPEF can help in
      developing new therapeutic strategies that will improve the prognosis of this
      syndrome. Until new evidence-based clinical data are available, treatment of
      HFPEF should remain multidisciplinary and individualized to each patient.

PMID- 19388495
TI  - Relative risk, absolute risk and number needed to treat: basic concepts.
AB  - The benefits of therapeutic interventions, whether pharmacologic, surgical,
      psychological, or others, are usually determined through clinical trials. The
      design of such trials involves the definition of a control group (placebo or
      active agent), which will be compared to one or more experimental groups (active
      agents). Benefits and/or harms are identified using so-called measures of
      association, including relative risk reduction (RRR), absolute risk reduction
      (ARR) and number needed to treat (NNT). This is the first of several papers on
      basic methodological concepts for analysis of the medical literature. We will
      present the concepts of RRR, ARR and NNT in a deliberately simple fashion, using
      published studies. On the basis of this knowledge the reader will be able to
      analyze the literature and make decisions based on it.

PMID- 19388496
TI  - Percutaneous aortic valvuloplasty in inoperable symptomatic severe aortic
      stenosis in the very elderly.
AB  - Aortic valve replacement is the first therapeutic option in patients with
      symptomatic severe aortic stenosis. Given the fact that percutaneous aortic valve
      implantation is a relatively new procedure and the need for palliative treatment
      in symptomatic patients with a high surgical risk, percutaneous balloon aortic
      valvuloplasty is still employed. The authors describe two cases of percutaneous
      balloon aortic valvuloplasty in very elderly patients with severe calcified
      aortic stenosis not suitable for cardiac surgery, exacerbated in one case by
      significant coronary artery disease and left ventricular systolic dysfunction.
      The authors also review the role of this procedure in current interventional
      cardiology.

PMID- 19388497
TI  - Adolescent with neurological manifestations of cardiac cause treated surgically.
AB  - Cardiac myxomas are a rare but important cause of embolic events and
      cerebrovascular disease in children and adolescents. The authors report the case
      of a 12-year-old girl with sudden dizziness and right-sided paresthesia of the
      lips and fingers of the right hand. She was observed by a pediatric neurologist
      and brain magnetic resonance imaging suggested demyelinating lesions or
      vasculitis. Echocardiography showed a left atrial mass compatible with an atrial
      myxoma. The myxoma was surgically removed without complications. This case
      highlights the need for cardiac evaluation to rule out a cardiac tumor with
      embolic potential in the presence of any child with neurological manifestations
      of cerebrovascular disease with inconclusive brain imaging, even with no previous
      evidence of cardiac disease. Prompt clinical recognition and surgical removal are
      essential to prevent serious complications.

PMID- 19388498
TI  - Complex ventricular septal rupture. The pivotal role of transesophageal
      echocardiography as support to surgery.
AB  - The authors report the case of a 73-year-old male with an inferior myocardial
      infarction and right ventricular dysfunction, evolving in Killip class IV. On the
      third day in the ICU cardiogenic shock ensued and septal rupture was diagnosed.
      Despite the severity of the setting and the poor prognosis, it was decided to
      operate. Intraoperative transesophageal echocardiography (TEE) disclosed a
      complex inferior septal rupture that was successfully repaired with a patch by
      the infarct exclusion method. Postoperatively, there was recurrence of the shunt
      with hemodynamic instability and a redo operation was programmed. Intraoperative
      TEE showed a partial tear of the anterior aspect of the patch and the suture was
      restored. The patient was discharged 45 days following admission, after
      transthoracic echocardiography (TTE) showed the integrity of the patch suture and
      full recovery of right ventricular function.

PMID- 19388499
TI  - Prosthetic aortic valve endocarditis with fistulization into the right atrium.

PMID- 19388500
TI  - Real-time 3D transesophageal echocardiography for the assessment of ventricular
      septal rupture.

PMID- 19388501
TI  - Medical-legal quandary of healthcare in capital punishment.

PMID- 19388502
TI  - Doctoral education: which degree to pursue?

PMID- 19388503
TI  - Bilateral transversus abdominis plane nerve blocks for analgesia following
      cesarean delivery: report of 2 cases.
AB  - These 2 case reports describe the use of transversus abdominis plane (TAP) nerve
      blocks for analgesia following emergency cesarean delivery. Bilateral single shot
      TAP blocks provided prolonged and extremely effective analgesia. Patients
      displayed early oral intake, early ambulation, and low pain scores. No
      postoperative narcotics were used by either patient throughout their hospital
      stay. A technique for TAP blocks is described with discussion of risks and
      suggested uses.

PMID- 19388504
TI  - Alpha2-adrenergic agonists and their role in the prevention of perioperative
      adverse cardiac events.
AB  - Alpha2-adrenergic agonists have been shown to reduce the incidence of
      perioperative myocardial morbidity and mortality. The purpose of this review
      article is to summarize the current data pertaining to alpha2-adrenergic agonists
      and their role in the prevention of perioperative adverse cardiac events. The
      MEDLINE and Cochrane databases were searched for randomized trials from 1980 to
      2006 that assessed perioperative alpha2-agonists and myocardial ischemia,
      myocardial infarction, and mortality. All recently published studies were
      reviewed and the data summarized. The currently published randomized controlled
      trials indicate that alpha2-agonists reduce the incidence of myocardial ischemic
      episodes in patients with known or suspected coronary artery disease undergoing
      noncardiac surgery, and clonidine was shown to reduce mortality in noncardiac
      surgical patients. The authors of the studies concluded that while alpha2
      agonists exert beneficial effects on hemodynamics and myocardial protection,
      large-scale, prospective, controlled trials are still needed.

PMID- 19388505
TI  - Preoperative fluid bolus and reduction of postoperative nausea and vomiting in
      patients undergoing laparoscopic gynecologic surgery.
AB  - We conducted a randomized clinical trial of patients undergoing laparoscopic
      gynecologic surgery to determine the effect of a calculated preoperative fluid
      bolus on postoperative nausea and vomiting (PONV). For the study, 46 women were
      randomly assigned to an experimental group, group 1, or a control group, group 2.
      Group 1 received up to 1,000 mL of replacement fluid preoperatively, using the 4
      2-1 formula. Group 2 received the anesthesia provider's routine replacement
      fluids. Neither group received antiemetics preoperatively or intraoperatively.
      All patients were assessed for PONV by nurses blinded to patient group
      assignment. Group 1 patients experienced significantly lower occurrences of PONV
      than did group 2 patients (P = .046). The preoperative fluid bolus seemed to be a
      significant factor in preventing PONV in group 1. Demographic and other factors
      reported to cause PONV, such as the length of surgery and major manipulation of
      the bowels, were similar in both groups. There was no significant difference
      between groups in reception of postoperative opioid, a known cause of PONV. Drops
      in blood pressure were thought to affect PONV, but group 1 patients had larger
      decreases in blood pressure than did group 2 patients.

PMID- 19388506
TI  - Anesthetic considerations for the patient with hereditary hemorrhagic
      telangiectasia (Osler-Weber-Rendu syndrome).
AB  - Hereditary hemorrhagic telangiectasia (HHT), Osler-Weber-Rendu Syndrome, is an
      uncommon disease but may be present in many people who remain undiagnosed. It is
      an autosomal dominant disorder characterized by multiple arteriovenous
      malformations (AVMs) and telangiectases that affect multiple organ systems.
      Hereditary hemorrhagic telangiectasia patients have a propensity for bleeding,
      especially from the oropharynx, nasopharynx and gastrointestinal tract, as well
      as from rupture of AVMs of other organ systems. Anesthetic care of patients with
      HHT involves very specific interventions with regard to control of bleeding,
      maintaining adequate oxygenation, and balancing hemodynamic values to optimize
      perfusion without compromising anesthetic depth.

PMID- 19388507
TI  - New estimates for CRNA vacancies.
AB  - A national survey to estimate vacancy rates of Certified Registered Nurse
      Anesthetists (CRNAs) in hospitals and ambulatory surgical centers was conducted
      in 2007. Poisson regression methods were used to improve the precision of the
      estimates. A significant increase in the estimated vacancy rate was reported for
      hospitals relative to an earlier study from 2002, although it is important to
      note that there were some methodological differences between the 2 surveys
      explaining part of the increase. Results from this study found the vacancy rate
      was higher in rural hospitals than in nonrural hospitals, and it was lower in
      ambulatory surgical centers. A number of simulations were run to predict the
      effects of relevant changes in the market for surgeries and number of CRNAs,
      which were compared to the predictions from the previous survey. The remarkable
      factor since the last survey was the unusually large rate of new CRNAs entering
      the market, yet the vacancy rates remain relatively high.

PMID- 19388508
TI  - Effect of timing of fluid bolus on reduction of spinal-induced hypotension in
      patients undergoing elective cesarean delivery.
AB  - Spinal-induced hypotension remains the most common complication associated with
      spinal anesthesia for cesarean delivery. Recent evidence indicates that a 20
      mL/kg bolus via pressurized infusion system administered at the time of
      subarachnoid block (SAB) (coload) may provide better prophylaxis than the
      traditional administration of a 20-mL/kg crystalloid infusion (preload)
      approximately 20 minutes before SAB; however, this method raises some concerns.
      We hypothesized that administering half of the fluid bolus (10 mL/kg) before and
      half immediately following injection of the SAB would provide benefit. Variables
      included demographics, spinal anesthetic dermatome level obtained, additional
      intravenous (IV) fluid bolus and vasopressor requirements, and maternal vital
      signs. We enrolled 87 subjects in this prospective, randomized investigation, 43
      preload (control) and 44 preload/coload (experimental). There were no demographic
      differences between groups. The increased supplemental vasopressors required to
      treat maternal hypotension in the preload group were not statistically
      significant. Total IV fluids and supplemental IV bolus requirements were
      significantly higher in the preload group. No differences in neonatal outcomes
      were noted between groups. Maternal vital signs were not significantly different
      between groups; hypotension was treated as it occurred. We recommend replacing
      standardized prophylactic crystalloid fluid administration with the
      preload/coload method described herein.

PMID- 19388509
TI  - Update for nurse anesthetists--Part 1--The cerebral oximeter: what is the
      efficacy?
AB  - Patients having surgical procedures are at risk for anoxia that may cause
      cognitive impairment. Continuous monitoring of cerebral oxygenation and perfusion
      with an instrument such as a cerebral oximeter is desirable. The data it provides
      give insight into the cause of the cerebral insults along with the cerebral
      response to specific interventions, all of which could help prevent damage to the
      brain. This critical review of the literature on the efficacy, mechanics, and
      usefulness of the cerebral oximeter will be helpful to anesthesia providers in
      evaluating the controversy surrounding its use. A comprehensive understanding of
      the factors involved in cerebral perfusion and available equipment, such as the
      cerebral oximeter to monitor cerebral oxygenation, allows anesthetists to provide
      the best protection for the brain.

PMID- 19388510
TI  - [Genetic base of esophageal squamous cell carcinoma susceptibility].
AB  - The esophageal squamous cell carcinoma is multifactorial disease involving
      genetic and environmental factors. The paper presents most important human data
      on the polymorphisms of selected genes that have been linked with higher risk of
      the neoplasm. The most widely studied group were genes encoded molecules engaged
      in biotransformations of xenobiotics, in particular potential carcinogens, like
      alcohol (ADH2) and aldehyde (ALDH2) dehydrogenases, various isoenzymes of
      cytochrome P450 (CYP1A1, CYP2E1) and glutathione S-transferase (GSTM1, GSTT1,
      GSTP1). High interest was also put for polymorphism in DNA repair genes, i.e.,
      OGG1, XRCC1, XPD, XPG and MGMT as well as genes associated with nucleotide
      biosyntesis like methylenotetrahydrofolate reductase and thymidylate synthase and
      in control of cell cycle and apoptosis e.g., p53, Fas, FasL or TNF. Furthermore,
      it was revealed that predisposition to cancer in certain individual could be
      determined by coexistence of unprofitable allele of a few genes. Introduction of
      genetic screening test allows effective, purpose-oriented methods of prevention
      and in patients suffered from the cancer--application of optimal therapy and
      minimization of side-effects.

PMID- 19388511
TI  - [The occurrence of anemia in small cell lung cancer patients during first-line
      chemotherapy].
AB  - Both the character of disease and its aggressive treatment--including cisplatin
      based chemotherapy--reflected to fact that anemia is a frequent problem in SCLC
      patients. Moreover, the potential prognostic role of anemia is considered in this
      group of patients. The aim of the study was to analyze occurrence of anemia in
      SCLS patients subjected to first line chemotherapy with the special attention
      paid to its potential prognostic role. MATERIAL AND METHODS: The retrospective
      analysis included 49 SCLS patients (including 22 and 27 LD and ED ones,
      respectively) treated in 2001-2004 at the Internal Disease Clinic in 4th Military
      Academic Hospital in Wroclaw Primary chemotherapy (cisplatin + etoposide) was
      performed in ED cases, whereas sequence treatment: chemotherapy (cisplatin +
      etoposide) with subsequent radiotherapy (including the elective irradiation of
      the central nervous system) was implemented in LD patients. Therapeutic results
      were evaluated in terms of response to treatment graded in accordance with RECIST
      criteria, time to progression (TTP) and overall survival (OS). Pretreatment
      anemia was identified based on the WHO criteria. Moreover, the maximal severity
      of anemia during the chemotherapy and the frequency of erythrocyte mass
      transfusions were taken into account. RESULTS: Pretreatment anemia (defined in
      accordance to WHO) was noted in 3/49 patients only. During the chemotherapy,
      however, it was noted in 21/49 cases (WHO grade I and II). The transfusion of
      erythrocyte mass was necessary in 9 patients, whereas the preparations of
      recombined erythropoietin were given in 3 cases. No prognostic role of anemia was
      proved in the group studied. The significant association, however, was noted
      between pretreatment anemia and PS according to WHO (p < 0.001). CONCLUSIONS:
      Anemia is a frequent problem during SCLC treatment and requires special therapy
      in most cases. The prognostic significance of anemia, however, is not fully
      understood, either in radical or in palliative treatment of SCLC patients. Our
      study revealed the lack of an association between anemia in prognosis.

PMID- 19388512
TI  - [Adhesion molecules of immunoglobin super family in children and youth with
      inflammatory bowel disease].
AB  - Chronic inflammation is the common feature of inflammatory bowel disease.
      Adhesion molecules of immunoglobin super family play a key role in infiltration
      of leucocytes to place of inflammation. THE AIM OF THIS STUDY: was to investigate
      the concentrations of slCAM-1, sVCAM-1 i sPECAM-1 in children and youth with
      Crohn's disease and ulcerative colitis. MATERIAL AND METHODS: The soluble
      adhesion molecules were studied in the serum of 31 patients with Crohn's disease
      (CD) and 27 with ulcerative colitis (uc) and 20 healthy controls in age 6-18.
      Groups of Crohn's disease and ulcerative colitis patients were divided according
      to Hyams and Truelove-Witts' indexes of disease activity. Serum levels of sICAM
      1, sVCAM-1 and sPECAM-1 were measured using an enzyme-linked immunosorbent assay
      kit of Bender MedSystem. RESULTS: There were no statistical significant
      differences in the levels of sICAM-1, sVCAM-1 and sPECAM-1 between the Crohn's
      disease patients and the control group. sICAM-1 level of the patients with
      ulcerative colitis was statistical significant higher then those of controls
      (391.28 +/- 134.95 ng/ml vs. 319.91 +/- 77.86 ng/ml, p = 0.022). There were no
      statistical significant differences in the levels of sVCAM-1 and sPECAM-1 between
      the patients with ulcerative colitis and the control group. There were no
      statistical significant differences in the levels of sICAM-1, sVCAM-1 and sPECAM
      1 between patients with the active Crohn's disease and with remission and between
      patients with active ulcerative colitis disease and with remission. CONCLUSION:
      Determine of sICAM-1, sVCAM-1 and sPECAM-1 in patients with inflammatory bowel
      disease could not be helpful in estimation of inflammation activity.

PMID- 19388513
TI  - [Genetic type of Helicobacter pylori and the efficacy of eradication therapy].
AB  - Helicobacter pylori is one of the most popular bacteria in the world. The H.
      pylori infection is an etiological factor of permanent changes in inflammatory of
      stomach mucous membrane, peptic ulcer of the stomach and duodenum disease and
      stomach cancer or mucosa associated lymphoid tissue from lymphoid tissue of
      mucous membrane. The strain bacteria which produce the protein CagA and cytotoxin
      VacA belong to the more pathogenic strains. The most successful method of
      treatment for H. pylori infection is an eradication of the bacteria. THE AIM OF
      THE STUDY: Was an evaluation of the influence which H. pylori genetic type (type
      I: CagA-positive, CagA-negative, VacA-positive, VacA-negative) has on efficacy of
      eradication therapy. MATERIAL AND METHODS: 214 of patients over the third year of
      life with symptoms of dyspepsia, of the upper part of the gastrointestinal tract
      was performed and H. pylori infection was proved in histopathological or (and)
      urease test and urea breath test. H. pylori identification was performed using
      PCR method for biopsy specimens of the gastric mucosa, estimating genetic type of
      the bacteria (CagA-positive, CagA-negative, VacA-positive, VacA-negative). Triple
      drug eradication therapy was introduced. The efficiency of this treatment was
      checked after 6 weeks with the breath test. RESULTS: The H. pylori infection was
      found in 101 patients (47.2%), 33 patients were infected with the strain type I
      (32.7%) and 68 patients (67.3%) with the strain type II. After the treatment the
      eradication of the infection was found at 71 patients (70.3%), lack of efficacy
      in H. pylori infection treatment was found at 30 patients (29.7%). Considerably
      higher percentage of eradicative infection was shown in the group of patients
      infected with the type II of H. pylori (76.5% vs. 58.8%, p < 0.04). CONCLUSIONS:
      The effectiveness of eradication can be influenced by the genetic type of H.
      pylori. The better effects of eradicative treatment can be expected if one is
      infected with the strains of smaller virulence.

PMID- 19388514
TI  - [Determination of milk and diary products consumption and their connection with
      lactose malabsorption or lactose intolerance in selected disorders of the
      alimentary tract in children].
AB  - Lactose stimulates proliferation and colonization of acidophilic bacteria, which
      due to fermentation processes lower colonic pH and simplified absorption of some
      microelements from the intestine. However, the common problem in children is
      intolerance of this carbohydrate. Treatment, quite simple, is based on partial or
      total elimination of lactose from diet. Some substitutional products with
      equivalent nutritional value should be introduced to prevent deficiencies
      symptoms during lactose-free diet. THE AIM OF THIS STUDY: Determination of milk
      and dairy products consumption and their connection with lactose malabsorption or
      lactose intolerance in children above 5 years of age in selected disorders of the
      alimentary tract: food allergy, celiac disease, secondary enteropathy, functional
      dyspepsia, irritable bowel syndrome and deficiency of body weight and height.
      MATERIAL AND METHODS: The number of 301 patients above 5 years of age (135 boys
      and 166 girls; mean age 11.5 years) were included into the study. Milk and dairy
      products consumption habits, lactose intolerance symptoms, hydrogen breath test,
      activity of lactase and villous atrophy were investigated. RESULTS: Decreased
      sweet milk consumption from, 33.33% in children with food allergy to 55.38% in
      children with functional indigestion was observed, in spite of gastrointestinal
      complaints after ingestion of milk. The biggest lactose malabsorption and lactose
      intolerance frequency was observed in children with decreased sweet milk
      consumption due to complaints after ingestion of milk and in children who didn't
      drink milk. There were no statistically significant difference between frequency
      of lactose malabsorption and lactose intolerance symptoms in children with
      different dairy products consumption habits. There were no statistically
      significant difference between frequency of hypolactasia in children with
      different sweet milk or dairy products consumption habits. CONCLUSIONS: Frequent
      (33-55%) decreased sweet milk consumption in children in spite of clinical
      symptoms after ingestion of milk was observed. The biggest lactose malabsorption
      and lactose intolerance symptoms frequency was observed in children who didn't
      drink milk and in children with decreased consumption of sweet milk due to
      complaints after ingestion of milk. There were no statistically significant
      difference between frequency of lactose malabsorption and lactose intolerance in
      children with different dairy products consumption habits.

PMID- 19388515
TI  - [The effectiveness of population-based breast cancer screening programme].
AB  - Well-organised mammography screening programme can significantly reduce the
      breast cancer mortality However, changes in mortality rates take a long time thus
      some early indicators are usually used to monitor the effectiveness of the
      programme. If these operational objectives are accomplished then the programme
      can replicate the mortality reduction achieved in randomised trials. THE AIM OF
      THIS STUDY: To evaluate the quality of breast cancer screening programme in the
      region of Lower Silesia during the first year of its operating. MATERIAL AND
      METHODS: Centrally organised breast cancer screening has been introduced since
      the beginning of the year 2007. This population-based programme is designed for
      women aged 50-69. Females undergoing treatment or being followed-up due to breast
      cancer are not invited. Screen-film two-view mammography without clinical
      examination is used as a screening test which is to be performed every two years.
      The second level diagnostic tools are breast clinical examination and additional
      imaging (mammography and ultrasound). Following further assessment women are
      referred to the examination at the routine round length of the programme, at the
      less interval (short-term recall) or biopsy procedures. Quality assessment was
      done via early indicators according to the European guidelines. RESULTS: The
      attendance rate was 41% (79,143 women screened within 192,613 eligible population
      for one year). Technical repeat rate, further assessment rate, and short-term
      recall rate were: 0.26%, 6.85%, and 0.91%, respectively. Pathologically confirmed
      breast cancer was revealed in 364 women giving the detection rate 4.59 for 1000.
      Cancer detection rate to expected incidence ratio was 3.35. CONCLUSIONS:
      Mammography service performed during the first year of breast cancer screening
      programme in the region of Lower Silesia conforms to quality assessment
      parameters recommended by the European guidelines at the acceptable level. The
      main problem at the start of this programme is too low coverage. Invitation
      process must be strongly intensified to improve long-term effectiveness and to
      significantly reduce breast cancer mortality.

PMID- 19388516
TI  - [Plasma homocysteine concentration in patients with ischaemic stroke caused by
      large or small vessel disease].
AB  - Homocysteine is known risk factor for the development of atherosclerosis, but its
      contribution to the different etiologies of ischaemic stroke remains unclear. THE
      AIM OF THE STUDY: Comparison of homocysteine, folic acid and vitamin 812 plasma
      concentrations in patients with ischaemic stroke due to large vessel disease
      (LVD), small vessel disease (SVD) and in controls. MATERIAL AND METHODS: We
      studied 71 patients with ischaemic stroke (including 30 patients with LVD and 41
      patients with SVD) as well as 30 control subjects. Aetiology of ischaemic stroke
      was established according to the TOAST criteria using computed tomography of the
      head, EKG, carotid ultrasound and echocardiography. In patients being 3-12 months
      after stroke we registered age, sex and the presence of common risk factors for
      stroke. The serum concentrations of homocysteine, folic acid, and vitamin 812
      were measured in venous blood samples drawn after the overnight fasting. RESULTS:
      Serum homocysteine concentrations were similar in patients with LVD, SVD, and in
      controls (19.5 +/- 8.9, 18.6 +/- 6.6, and 16.8 +/- 6.4 micromol/l, respectively)
      (p = 0.36, ANOVA). Vitamin 812 concentrations did not differ significantly among
      patients with LVD, SVD, and in controls (377 +/- 143, 414 +/- 179, and 412 +/-
      173 pg/ml, respectively) (p = 0.66, ANOVA). Patients with LVD, SVD, and controls
      were also similar regarding the concentrations of folic acid (7.1 +/- 4.0, 6.4 +/
      2.7, and 7.6 +/- 4.0 ng/ml, respectively) (p = 0.38, ANOVA). CONCLUSION: Serum
      concentrations of homocysteine, vitamin 812, and folic acid are similar in
      patients with stroke due to LVD, SVD, and in control subjects.

PMID- 19388517
TI  - [Inflammatory fibroid polyp of the stomach--a case report].
AB  - Inflammatory fibroid polyp of the stomach is a rare benign mass of unknown
      etiology, mostly located within the pyloric area. Histopathological findings
      mainly reveal the presence of mononuclear fusiforme cells forming loose extensive
      bundles or rotary structures of rotated spirals with abundant amount of
      eosinophilic cytoplasm. These cells are negatively stained for S-100 protein and
      desmine and positively stained for CD-34. Symptoms of the disease depend on the
      localization and the size of the polyp. We report a case of 50-year-old woman
      with a large inflammatory fibroid polyp with a diameter of 60 x 50 x 40 mm
      imitating benign gastric tumour. She mainly suffered from abdominal pain and lab
      tests revealed symptoms of severe anaemia. We performed partial gastrectomy with
      Hofmeister-Finsterer modification. Postoperative pathological findings certified
      sings of inflammatory fibroid polyp. During the two year followup period we did
      not report any signs of recurrence or dissemination. Clinical manifestation of
      large inflammatory fibroid polyp of the stomach can imitate symptoms of gastric
      cancer. Partial gastrectomy with an unaltered, healthy wall margin of 2 to 3 cm
      is sufficient, curative treatment modality in such cases.

PMID- 19388518
TI  - [Proximal migration of pancreatic "pig tail" stent--a case report].
AB  - Proximal migration of pancreatic stents it's serious problem which can need the
      extensive surgery with following egzo- and endocrine insufficiency. Therefore the
      possibility of endoscopic solution of mentioned problem is very important. The
      purpose of this publication is presentation the case of proximal migration "pig
      tail" pancreatic stent and endoscopic technique removal it. Simultaneously was
      executed the literature review relating to factors influencing on migration, and
      also the endoscopic methods enabling the solution of presented complication.

PMID- 19388519
TI  - [Diagnostics of cat scratch disease and present methods of bartonellosis
      recognition--a case report].
AB  - Bartonella infections including cat scratch disease (CSD) is a group of
      infectious diseases which are diagnosed sporadically. Because of this fact the
      number of CSD cases in Poland is underestimated and their incidence is markedly
      lower in comparison to other European countries. The aim of our report is to
      present various diagnostic methods and possibilities on the basis of two cases
      with symptoms of CSD. The efficiency of specific Bartonella antibiotic therapy is
      also discussed.

PMID- 19388520
TI  - [Does diet affect our mood? The significance of folic acid and homocysteine].
AB  - In recent years, there has been growing interest in the association between
      national diet and the possibility of developing various mental disorders, as well
      as between deficiency of such vitamins as, e.g. folic acid, vitamin B12, B6, and
      others (e.g., omega-3 fatty acids), elevated serum homocysteine level and the
      functioning of human brain as well as the occurrence of such disorders as
      dementia, central nervous system vascular disorders and depression. THE AIM OF
      THE STUDY: was to present the current state of knowledge about the role of folic
      acid and homocysteine in the human organism as well as the significance of
      vitamin deficiency, mainly folic acid and hyperhomocysteinemy for the occurrence
      of mood disorders. METHOD: The authors conducted the search of the Internet
      database Medline (www.pubmed.com) using as key words: depression, mood,
      homocysteine, vitamin deficiencies: folic acid, B6 and 812 and time descriptors:
      1990-2007. RESULTS: In depression, folate, vitamins B12 and B6, as well as
      unsaturated omega-3 fatty acids deficiency affects the biochemical processes in
      the CNS, as folic acid and vitamin B12, participate in the metabolism of S
      adenosylmethionine (SAM), a donator of methyl groups, which play a decisive role
      in the functioning of the nervous system; they are, among others, active in the
      formation of neurotransmitters (e.g. serotonin), phospholipids that are a
      component of neuronal myelin sheaths, and cell receptors. The deficiency of the
      vitamins in question results in hyperhomocysteinemia (the research shows that
      approximately 45-55% of patients with depression develop significantly elevated
      serum homocysteine), which causes a decrease in SAM, followed by impaired
      methylation and, consequently, impaired metabolism of neurotransmitters,
      phospholipids, myelin, and receptors. Hyperhomocysteinemia also leads to
      activation of NMDA receptors, lesions in vascular endothelium, and oxidative
      stress. All this effects neurotoxicity and promotes the development of various
      disorders, including depression. Vitamins B12 and B6, folic acid and omega-3
      fatty acids supplementation is thus important in patients suffering from their
      deficiency; national diet as a significant factor in prevention of numerous CNS
      disorders, including depression, is also worth consideration.

PMID- 19388521
TI  - [Hypercortisolism and hemostasis].
AB  - Endocrinopathies can cause various changes in coagulation and fibrinolytic
      mechanisms. Glucocorticoids show particulary important influence on hemostasis.
      Increased tendency to thromboembolic incidents is observed in either endogenous
      hypercortisolism or glucocorticoids administration. The aim of this paper was to
      present the hemostatic disturbances in patients with hypercortisolism, with
      particular emphasis in their development on metabolic changes, endothelium
      damage, influence of pro-inflammatory cytokines and hiperhomocysteinemia. The
      problem of anticoagulant prophylaxis in this group of patients is also discussed.

PMID- 19388522
TI  - [Genetic polymorphisms of oxidation and acetylation in cancers of digestive
      system].
AB  - Cancer diseases are the second most common cause of mortality in Poland. The
      cancers of digestive system: colorectal cancer, gastric cancer, pancreatic cancer
      and liver cancer are the first common malignant tumour. Pathogenesis of cancer
      diseases is connected with influence of environmental factors with individual
      dependent among others on detoxification enzymes. Genetic differences in the
      regulation, expression and activity of genes coding for phase I and phase II drug
      metabolizing enzymes can be crucial factors in defining cancer of digestive
      system susceptibility. In this review our current knowledge about polymorphism in
      several of these genes is summarized.

PMID- 19388523
TI  - [Lactose intolerance: pathophysiology, clinical symptoms, diagnosis and
      treatment].
AB  - Lactose malabsorption and milk products intolerance symptoms are the most common
      alimentary tract disorders. Lactose intolerance is a result of lactase deficiency
      or lack of lactase and lactose malabsorption. Three types of lactase deficiency
      were distinguished: congenital, late-onset lactase deficiency and secondary
      lactase deficiency. Lactose intolerance means the appearance of clinical
      gastrointestinal symptoms after ingestion of lactose. To the clinical symptoms of
      lactose intolerance belongs: nausea, vomiting, abdominal distension, cramps,
      flatulence, flatus, diarrhea and abdominal pain. The diagnosis of lactose
      intolerance is based on the breath hydrogen test and analysis of lactase activity
      in the small intestine mucosa. Dietary treatment eliminates clinical symptoms.

PMID- 19388524
TI  - [Diagnosis of biliary leakage after laparoscopic cholecystectomy in aspect of
      indication to endoscopic treatment].
AB  - Clinically significant biliary leak (BL) following laparoscopic cholecystectomy
      (LCH) occurs in fewer than 5% patients, nevertheless, due to nonspecific symptoms
      and low diagnostic accuracy in commonly available imaging modalities, may
      constitute a diagnostic problem. Penetration of pure bile to peritoneal cavity
      does not product specific symptoms and signs and can be detected by sonography
      only in 58% patients. In addition, distinguishing between bile and other fluid is
      possible only by cholescintigraphy (CS). Thus, accurate diagnosis in early
      postoperative period may be difficult and may delay adequate treatment. Because
      of that, despite the current tendency to avoid drainage after elective LCH, it
      appears to be a simple method for early detection of the above pathology and
      determining of need for endoscopic retrograde cholangiopancreatography (ERCP).

PMID- 19388525
TI  - [Natural compounds in chemoprevention of esophageal squamous cell tumors-
      experimental studies].
AB  - Chemoprevention refers to prevention of tumor formation due to administration of
      nontoxic synthetic or natural compounds, which can block or weaken the influence
      of carcinogens on target cells or even reverse previously formed lesions. In
      esophageal squamous cell carcinoma--which belongs to the group of the most
      aggressive tumors of digestive system with poor prognosis--an effective
      prevention would be strongly expected. Chemopreventive properties of many complex
      diets and pure natural compounds were evaluated until now. Most studies were
      performed on rats exposed to chemical carcinogens, usually N-nitroso-N
      methylbenzylamine (NMBA). The best effects were achieved after administration of
      diallyl sulfide and phenethyl isothiocyanate. Lyophilized black raspberries,
      blackberries and strawberries, as well as products obtained from leaves and buds
      of tea plant, elagic acid and resveratrol were also very effective. Mechanisms of
      chemopreventive action were associated with, i.e., activity of enzymes involved
      in carcinogen metabolic activation (mostly cytochrome P450 isoenzymes),
      inhibition of DNA adducts formation and modulation of gene expression involved in
      regulation of proliferation, apoptosis and angiogenesis. However, some agents
      e.g., perillyl alcohol, could enhance development of proliferative lesions in
      esophageal epithelium.

PMID- 19388526
TI  - [Cytoprotection--protective agents and mechanisms of their activity in the cell].
AB  - Cytoprotection can be defined as the ability to protect cells against wide
      variety of damaging agents. A series of recent studies indicate that many
      substances participate in this process. It has been proved that different
      mechanisms as inhibition of oxidative stress or apoptosis mediate in
      cytoprotection. However, a number of mechanisms responsible for this extremely
      compound process remain still unknown. In this revew we discuss the scientific
      evidence documenting cytoprotective agents and pathways of their activity.

PMID- 19388527
TI  - [The role of Langerhans cells in the skin immune system].
AB  - Langerhans cells (LC) are members of the dendritic cells family, residing in the
      basal and suprabasal layers of the epidermis and in the epithelia of the
      respiratory, digestive and urogenital tracts. They specialize in antigen
      presentation and belong to the skin immune system (SIS). LC acquire antigens in
      peripheral tissues, transport them to regional lymph nodes, present to naive T
      cells and initiate adaptive immune response. LC have strong immunogenic
      properties but they may also act as mediators of tolerance, for example to
      comensal bacteria. They are involved in antimicrobial immunity, skin
      immunosurveillance, induction phase of the contact hypersensitivity and in the
      pathogenesis of chronic inflammatory diseases of the skin or mucosa. We present
      the current knowledge of Langerhans cells' role in the skin immune system.

PMID- 19388528
TI  - [Control of asthma symptoms and cellular markers of inflammation in induced
      sputum in children and adolescents with chronic asthma].
AB  - After the GINA 2006 publication, asthma therapy is based on control of symptoms.
      However there are suggestions of monitoring of airway inflammation. Aim of the
      study was to compare clinical criteria of asthma control with cellular markers of
      lower airway inflammation in induced sputum in a group of young asthmatics. To
      assess relationship between sputum eosinophilia, asthma severity and spirometry.
      MATERIAL AND METHODS: A group of 154 young patients with chronic asthma (8-21
      years) underwent sputum induction by inhalation of 4,5% saline solution. Sputum
      induction was effective in 121 patients (78%), and in this group control of
      clinical symptoms was assessed according to GINA 2006 criteria. RESULTS: Asthma
      was controlled in 82 subjects (67.8%) and uncontrolled in 39 (32.2%). Patients
      with controlled asthma had higher FEV1/FVC (79.8 +/- 7.1% vs 74.2 +/- 9.9%; p =
      0.004) and MMEF (80.7 +/- 23.0% vs 65.3 +/- 21.8%; p < 0.001) than those with
      uncontrolled disease, but the average FEV1 (as percent predicted) did not differ
      between the two groups. Patients with controlled asthma had lower sputum
      eosinophil count than those with uncontrolled asthma (3.5 +/- 6.3% vs 7.2 +/-
      8.7%; p = 0.01), but difference in neutrophil count was borderline (27.3 +/-
      15.5% vs 34.5 +/- 21.0%; p = 0.05). High sputum eosinophil count (> 3%) was
      observed in 24.4% of patients with controlled asthma and in 61.5% with
      uncontrolled asthma (p < 0.001). Increased sputum neutrophil count was more
      frequent in a group of uncontrolled asthma (2.4 vs 15.4%; p = 0.022). Mean sputum
      eosinophil count was lower in patients with mild astma than in patients with
      moderate-severe disease (3.1 +/- 5.7% vs 7.1% +/- 8.8; p = 0.006). Patients with
      high sputum eosinophil count had lower FEV1 (89.4 +/- 14.9% vs 94.9 +/- 13.9%; p
      = 0.047), FEV1/FVC (74.5 +/- 10.1% vs 79.2 +/- 9.3%; p = 0.01) and MMEF (68.7 +/-
      23.3% vs 81.7 +/- 23.1%; p = 0.004). CONCLUSIONS: In this study of young
      asthmatics, control of asthma symptoms was observed in 67.8% of patients.
      However, cellular markers of lower airway inflammation were present in 1/4 of
      patients with controlled asthma and in 3/4 with uncontrolled disease. Sputum
      eosinophilia was related to asthma severity. FEV1/FVC and MMEF were more
      important that FEV1 for estimating control of asthma. Improvement of asthma
      control scoring is needed as well as availability of simple methods of
      inflammation monitoring.

PMID- 19388529
TI  - [Analysis of L, E, and P selectins concentration in infants and young children
      with spastic bronchitis].
AB  - Spastic bronchitis in infants and young children is one of the most frequent
      causes of hospitalization in this age group. Both infectious and allergic
      inflammations lead to inflammation cells activation and their flow to the place
      of inflammation by the activation of adhesive molecules. One of groups of
      adhesive molecules are L, E and P selectins responsible for leucocytes migration
      through the vessel wall. The aim of the study was to assess the concentration of
      solved fractions of L, P and E selectins in infants and young children in the
      course of spastic bronchitis. MATERIAL AND METHODS: Fifty four patients with
      spastic bronchitis (group I) including 32 with the first bronchitis (group IA)
      and 22 patients with recurrent bronchitis (at last the third one--group IB) were
      included into the study. Comparative group (group II) was consisted of 26
      patients hospitalized due to other causes and with no bronchitis in the past.
      Patients were from 1 to 36 months of age. Among all patients solved fractions of
      selectins L, E and P were analyzed by ELISA tests. RESULTS: Mean sL-selectin
      concentration in group I was 4126.3 ng/ml and in group II 4222.31 ng/ml and was
      not statistically significant. Concentrations of sL-selectin in the group of
      patients with the first episode of spastic bronchitis was 4099.37 ng/ml and in
      the group of patients with recurrent bronchitis was 4166 ng/ml and had no
      statistical difference. Mean sE-selectin concentration in group I was 205.49
      ng/ml and in group II 214.50 ng/ml and was not statistically significant.
      Concentrations of sE-selectin in the group of patients with the first episode of
      spastic bronchitis was 195.22 ng/ml and in the group of patients with recurrent
      bronchitis was 220.43 ng/ml and had no statistical difference. Concentration of
      sP-selectin was assessed among 51 patients with bronchitis and among 26 patients
      from comparative group. Because of the lack of normal distribution values of sP
      selectin concentrations were changed by decimal logarithm. Mean sP-selectin
      concentration in group I was 235.95 ng/ml and in group II 164.70 ng/ml. After
      logarithm change values of concentrations were: 2.249 and 2.005 and had
      statistical difference (p = 0.0221). Concentrations of sP-selectin in the group
      of patients with the first episode of spastic bronchitis was 234.0 ng/ml and in
      the group of patients with recurrent bronchitis was 238.20 ng/ml and after
      logarithm change concentrations were 2.26 in the group of patients with the first
      episode of spastic bronchitis and 2.24 in the group of patients with recurrent
      bronchitis and had no statistical difference. CONCLUSION: On the ground of our
      study in infants and young children with spastic bronchitis increase of sP
      selectin concentration was observed and sE-selectin and sL-selectin
      concentrations were the same.

PMID- 19388530
TI  - [Sleep disorders in childhood and adolescence, with special reference to allergic
      diseases].
AB  - Allergic diseases have a significant impact on the quality of life. The aim of
      the study was to compare sleep parameters of allergic and non-allergic children.
      MATERIAL AND METHODS: Pediatric Sleep Questionnaire was used to asses sleep
      quality in 202 participants in a 3-year prospective study: in 122 hospitalized
      (mean age 7.9 +/- 4.7) (F/M 75/47) due to allergic (n = 70) or non-allergic
      disease (n = 52), and in 80 healthy children (mean age 6.3 +/- 5.0) (F/M 36/44).
      Of 70 allergic participants, 26 had atopic dermatitis (SCORAD > or = 20); 25 were
      with bronchial asthma (GINA' criteria) and 19 with IgE-dependent food allergy
      confirmed by oral food challenge. Of 52 non-allergic patients, 31 children had
      gastro-esophageal reflux disease and 21 children had recurrent respiratory
      infection. RESULTS: The group of patients needed significantly more time to fall
      asleep than controls (17.9 +/- 13.7 vs 12.8 +/- 8.5 min; p < 0.004). Children
      with food allergy and atopic dermatitis had greatest problems with falling asleep
      (21.4 +/- 13.8 vs 12.8 +/- 8.5 min; p < 0.006) and 20.4 +/- 14.9 vs 12.8 +/- 8.5
      min; p < 0.024). The number of nights of sound sleep without waking up was lower
      in the study group than in controls (3.5 +/- 2.6 vs 5.0 +/- 2.7; p < 0.0002).
      Atopic dermatitis and food allergy were found to predispose to sleep disruption
      most. Snoring history was revealed in 43.4% of patients and in 6.4% of controls
      (p < 0.0001), being significantly more common in children with bronchial asthma
      and recurrent respiratory tract infections. Allergic disease was a risk factor
      for snoring (OR--2.94; 95%CI--1.72-5.05; p < 0.001). As many as 91% of parents
      did not inform doctors about poor sleep of their children. CONCLUSIONS: 1.
      Allergic diseases are accompanied by different sleep disorders included
      dyssomnias and parasomnias, e.g. bedtime resistance, disrupted sleep or sleep
      disordered breathing. 2. Physicians should pay particular attention to sleep
      quality in children with allergic diseases irrespective of which body system is
      affected i.e. the skin (atopic dermatitis), the respiratory tract (bronchial
      asthma) or the alimentary system (food allergy).

PMID- 19388531
TI  - [Serum activity of chitotriosidase, lysozyme and cathepsin H in patients with
      lung cancer and patients with inflammatory exudate (preliminary report)].
AB  - Lung cancer remains the leading cause of cancer death over the world. Although
      new diagnostic methods have been discovered, new biomarkers of the cancer are
      still under studying. A human chitinolytic enzyme called chitotriosidase
      hydrolyzes chitin and chitotrioside substrates. It is specifically expressed by
      activating macrophages and seems to play a role in the defense against chitinous
      human pathogens. Recently it has been shown that chitotriosidase may also attend
      to the inflammatory process. The aim of the study was to determine
      chitotriosidase activity in serum of patients with lung cancer and patients with
      inflammatory exudate. We studied the usefulness of the above parameter
      determination in differentiation between lung cancer and inflammation. In
      addition, serum activity of lysozyme and cathepsin H was determined. MATERIALS
      AND METHODS: The study included 17 patients with inflammatory pleural exudate-
      group 1., 40 lung cancer patients with malignant pleural effusion--group 2. and
      37 healthy subjects. All the patients of group 2. were divided into 2 subgroups:
      2A without metastases (n = 23) and 2B with metastases (n = 17). Chitotriosidase
      and cathepsin H activity was determined in serum by a fluorometric methods. Serum
      lysozyme activity was measured by turbidimetric method with Micrococcus luteus as
      substrate. RESULTS: We observed an increase of the chitotriosidase activity in
      serum patients of both studied group in comparison with the control. The activity
      of the chitotriosidase in lung cancer patients was significantly higher than in
      the control (36.7 vs 68.1 nmol/ml/h; p < 0.01). There were no significant
      differences in serum lysozyme and cathepsin H activity in patients in comparison
      to healthy subjects. CONCLUSION: The results suggest that activity of the
      chitotriosidase can not be used to differentiation between inflammation and
      cancer in lung.

PMID- 19388532
TI  - [Simvastatin therapy and effect on hiperlipidemia and vascular status in
      nephrotic children with sustained dyslipidemia].
AB  - Dyslipidemia is common in nephrotic children and persistent lipid abnormalities
      are risk factor of late vascular complications. The aim of the study was
      evaluation of efficacy and safety of 12-months simvastatin therapy in nephrotic
      children with lipid profile abnormalities present despite clinical remission
      lasting for at least 8 weeks, including ultrasonographic assessment of carotid
      and femoral arteries. MATERIAL AND METHODS: Overall 52 children (40 steroid
      dependent and 12 steroid-resistant) were initially introduced to the study and 29
      of them were treated with simvastatin. Normalisation of lipid profile was
      achieved in 19/29 (65.5%) and improvement in 9/29 (31%). Significant reduction in
      total cholesterol (p < 0.00001), LDL-C (p < 0.000003), VLDL- (p < 0.0123), oxy
      LDL-C fractions (p < 0.0002) and triglycerides (TG) (p < 0.0005) serum
      concentration was achieved in non-proteinuric patients. RESULTS: Analysis of the
      intima-media thickness (IMT) of the common carotid (c) and superficial femoral
      (f) arteries values revealed positive correlation between baseline cIMT and VLDL
      C (p = 0.038) and TG concentration (p = 0.008), as well as positive correlation
      between fIMT and baseline creatinine (p = 0.04) and LDL-C serum concentration (p
      = 0.032) after simvastatine treatment. Number of children with significant
      vessels pathology (Z-score > 2.0) was small. Increased cIMT was seen at baseline
      in 4 patients and in 5 after simvastatin treatment, however average and Z-score
      values in children under simvastatin treatment have decreased. Increased fIMT
      values were seen at baseline in 2 and in one case after simvastatin treatment.
      Tolerance of simvastation was very good in all cases but one. CONCLUSION:
      Simvastatin therapy was effective and safe in nephrotic non-proteinuric children
      with abnormal lipid profile. Fair estimation of impact of the 12-months
      simvastatin therapy on vascular status was not available due to limited number of
      children with significantly increased IMT at baseline.

PMID- 19388533
TI  - [Effectiveness of rehabilitation in multiple sclerosis].
AB  - Multiple sclerosis is progressing demielinization syndrome of central nervous
      system. Changes in CNS correlated with clinical symptoms of neurological
      deficiency with different progress (according to kind of clinical type). Often
      lead to disability. Etiology of MS wasn't competently known till now. It wasn't
      worked completely effective treatment of this syndrome. The aim of this study was
      to examine the effectiveness of rehabilitation in MS. It was done by using three
      scales: functional estimation--ADL scale, muscle strength--Lovett scale and
      estimation of disability by EDSS. MATERIAL AND METHOD: 84 patients, average age
      48 years with completely diagnosed multiple sclerosis (ICD-10 G35) rehabilitated
      in the Rehabilitation Department at the III Provincial Hospital in Lodz.
      Examination in over mentioned scales was done before start treatment and after
      finished rehabilitation. Finally examination of significantly of examined
      distinguishes done by statistical analysis and accurately by verification
      hypotheses about significantly results differences between particular periods of
      rehabilitation, next t-Student test was used for two statistical samples.
      RESULTS: Statistical analysis showed very significant progress after using
      rehabilitation on the level of significance 0.00001 in all used scales.
      CONCLUSIONS: Comprehensive rehabilitation significantly influenced on functional
      improve patient with multiple sclerosis and decrease disability score.

PMID- 19388535
TI  - [What the nephrologist should know about antiphospholipid syndrome?].
AB  - Antiphospholipid syndrome is often recognize autoimmune disease associated with
      arterial and venous thrombosis and pregnancy loss. It is caused by antibodies
      against proteins combined with cell membrane anionic phospholipids. Kidney are
      one of the most often affected organs in course of antiphospholipid syndrome.
      Renal manifestations include thrombotic microangiopathy and large vessel
      thrombosis. In patients with end-stage renal disease, antiphospholipid antibodies
      are prevalent and may increase in frequency with time on dialysis. The presence
      of anticardiolipin antibodies have been associated with high incidence of
      hemodialysis access clotting. In renal transplant recipients, the incidence of
      antiphospholipid antibodies is also elevated and may be associated with higher
      incidence of primary graft non-function. Treatment of antiphospholipid syndrome
      remains centered around anticoagulation. The use of immunosuppressive agents
      could be very useful. Early detection of renal involvement and treatment may
      improve the prognosis of these patients.

PMID- 19388534
TI  - [Costs of exacerbations of chronic obstructive pulmonary disease in primary and
      secondary care in 2007--results of multicenter Polish study].
AB  - OBJECTIVES: Exacerbations are the key drivers of the costs of chronic obstructive
      pulmonary disease (COPD). This was the multicenter study of patients with COPD
      aimed at evaluating direct and indirect cost of exacerbations under usual
      clinical practice in primary and secondary care form societal perspective.
      METHODS: It was observational, multicenter study with participation of 196
      subjects with moderate or severe COPD, defined according to the current GOLD
      criteria. Patients presenting at the selected health care centres were included
      into the study in the sequential manner if they fulfilled the inclusion criteria.
      Exacerbations were divided into three different severity types according to
      Anthonisen N.R. classification. The management of exacerbations followed the
      usual clinical practice. RESULTS: The number of exacerbations was 3.8 (3.2-4.4)
      in hospitalised patients and 1.7 (1.4-1.9) in ambulatory treated patients (1EURO
      was 3.85 PLN in 2007). The average direct health-care cost per exacerbation was
      PLN 5548 (95% CI = 4543; 6502) and PLN 524.1 (95% CI = 443; 614) in secondary and
      primary care respectively. In secondary care, the drug acquisition and oxygen
      therapy cost represented 18.3% of total direct costs, diagnostic tests costs
      accounted for 14.5%, the other hospital care and post-discharge followup visit
      costs 67%. Costs varied considerably with the severity of COPD before the
      exacerbation as well as the duration of COPD. In primary care the cost structure
      was as follows: diagnostic tests and medical devices 47.5%, drug acquisition
      costs 41% and doctors visits 11.4%. The average indirect costs per exacerbation
      were PLN 127.78 and PLN 100.56, in secondary and primary respectively (n.s)
      CONCLUSION: Exacerbations of COPD are costly. Cost of exacerbation managed in
      secondary care is almost 10-fold higher than in primary care. Prevention of
      moderate-to-severe exacerbations, requiring hospitalization could be very cost
      effective strategy.

PMID- 19388536
TI  - [Education in peritoneal dialysis].
AB  - Successful treatment with peritoneal dialysis (PD) depends in great degree on
      good training of a patient or her/his assistant by properly educated medical
      staff. The presented paper focuses on rules concerning education of nurses and
      patients in the field of PD. It includes purposes and program of education, a
      choice of place and duration of training as well as methods of checking of
      education effectiveness. Education of nurses has to be complex, because they
      should be able to work not only in a hospital under direct supervision of a
      nephrologist, but also relatively selfish. Attention is paid for having printed
      descriptions of all PD procedures always available in educating unit and for
      avoiding the performance of PD procedures in patients by nurses still in training
      (nurses should do exercises on manikins until they obtain perfect performance of
      PD procedures). Main principles of patient' education include training by one
      nurse, action on various forms of perception (written information, pictures, oral
      communication, touching), using methods the best fitting to individual patient'
      ability (for example, elimination of written materials in patients, who have
      troubles with reading). All procedures, in which patients are trained, should be
      available for them in written form and/or pictures. Effects of the education
      quality should be periodically checked. Evaluation of the education quality is
      based on results of PD treatment and includes: 1) peritonitis and exit site
      infection rates, 2) frequency of unplanned admissions to hospital and visits in
      ambulatory health care, 3) costs of treatment of PD complications.

PMID- 19388537
TI  - [Sequences of human immunodeficiency virus infection (HIV)].
AB  - The clinical profile of HIV infection has changed from lethal disease, gradually
      destroying patient's immunologic system and progressing inevitably to AIDS, into
      a chronic manageable condition as it is now. The introduction of combined
      antiretroviral therapy in 1996 dramatically improved prognosis. In developed
      countries the estimated survival for a young person diagnosed with HIV infection
      in the late highly active antiretroviral therapy approaches the survival of
      general population. Despite the benefits of early diagnosis, majority of people
      living with HIV are unaware of their HIV status. Both poor knowledge of
      transmission routes and long asymptomatic phase of the infection contribute to
      delayed diagnosis. When the disease progresses towards symptomatic phase many
      patients seek help of physicians of varied specialities. The correct diagnosis of
      HIV infection being the cause of the reported symptoms depends on physicians'
      knowledge of HIV clinical features. In the age of combined antiretroviral therapy
      the diagnosis of HIV infection saves patient's life, and in case of pregnant
      women it additionally decreases significantly the risk of vertical transmission.

PMID- 19388538
TI  - [Post Lyme syndrome as a clinical problem].
AB  - Lyme disease is a chronic tick borne disease, caused by spirochetes B.
      burgdorferi. The condition influences mostly on skin, nervous system, skeletal
      system and circulatory system. Recently more and more reports of so called "Post
      Lyme syndrome (PLS)" have appeared. PLS is a new clinical, diagnostic and
      therapeutic problem connected with patients with a history of Lyme disease (with
      proper antibiotic treatment). The symptoms of Post Lyme Syndrome may be present
      throughout months or even years. These are: fatigue, widespread musculoskeletal
      pain, dysmnesia, concentration difficulties. Pathogenesis of PLS is unknown. It
      is suspected that main factors responsible for PLS are: slow regression of
      infection, its turning into chronic process and permanent destruction of tissues
      or induction of immunological response against B. burgdorferi. Diagnostic of PLS
      is difficult. Mostly results of serological examination are negative. In some
      cases antibodies titer is positive as a sign of past disease. So far there is no
      causative treatment of PLS. Antidepressants, painkillers and anti-inflammatory
      medicines are recommended.

PMID- 19388539
TI  - [Pharmacotherapy for pelvic endometriosis in women].
AB  - Pelvic endometriosis in women is a very common disease. The incidence of this
      condition in Poland in reproductive age women is about 7-15%, and as much as 50%
      of cases is diagnosed in patients with co-existing infertility and/or pain and
      adhesion of a true pelvis. The choice of a therapeutic method depends on the
      patient's age, stage of the disease, desire for pregnancy, the presence of
      adhesion, focus localization and a reaction to previous treatment. Currently, the
      most popular is surgical treatment sometimes followed by pharmacotherapy.
      Pharmacological treatment includes hormone therapy and symptomatic treatment,
      also the use of painkillers. Hormonal agents are administered to suppress ovarian
      activity and cause atrophy of ectopic foci of endometrium. At present, post
      surgical pharmacotherapy for endometriosis uses mainly such hormones as: the
      Combined Oral Contraceptive Pill (COCP), progestagens, danazol, GnRh
      (gonadotropin-releasing hormone) analogues, aromatase inhibitors and other less
      common drugs. Also other therapeutic procedures are recommended in endometriosis
      treatment, procedures which support and in certain clinical situations even
      replace classical pharmacological methods. Some of them are immunotherapy and a
      diet rich in isoflavones, organic compounds which modulate estrogen receptor
      activity. Numerous clinical trials proved that preoperative pharmacotherapy does
      not improve treatment results and is not applicable to endometriomas in women. On
      the other hand, postoperative pharmacotherapy still ignites controversy. As
      maintained by the most recent literature, in the case of mild endometriosis
      (clinical Stage I and II according to the American Society for Reproductive
      Medicine) endometrial ablation has better effects than observation only, however
      postoperative pharmacotherapy does not improve the results of treatment. In more
      severe cases (clinical Stage III and IV), the best results are achieved by the
      combined treatment. Nevertheless, no randomized research has been carried out on
      a wide scale in this group of patients.

PMID- 19388540
TI  - [Immunomodulatory proteins in colostrum].
AB  - The value of bovine colostrums is documented in clinical observations and
      supported by large database. An antibacterial effect and modulation of the immune
      response are accepted. The wide spectrum of the activity of a lactoferrin or a
      proline-rich polipeptide complex was confirmed in experimental and clinical
      studies. Moreover, a high concentration of immunoglobulins in bovine colostrum
      gives exceptional opportunity for use it as a support in immunodeficiency
      treatment.

PMID- 19388541
TI  - [Selected issues regarding implementing alternative medicine with special
      reference to the patients with laryngological problems].
AB  - The review of the literature and some media data referring to chosen methods of
      unconventional treatment, its history of the development in Poland and around the
      world has been made in this paper (homeopathy, waxing of ears, bio-energy
      therapy) and the increasing interest among the treated patients has been shown.
      It is essential that the doctors (including laryngologists) while carrying out
      the interview should take the unconventional way of treatment of patients into
      consideration. This may explain the registering of patients to appropriate
      treatment in the advanced state of illness, which is particularly unprofitable in
      cancer-afflicted states.

PMID- 19388542
TI  - [The influence of hyperglycemia on functions of endothelial progenitor cells].
AB  - The isolation of endothelial progenitor cells changed our understanding of adult
      blood vessel formation. Recent studies have proven that EPCs functionally
      contribute to neovasculogenesis and reendothelization of damage blood vessels. It
      has been shown that patients with diabetes mellitus have decreased numbers of
      EPCs with impaired activities important to growth of blood vessels. It has been
      demonstrated that hypoglycemia cause abnormalities in EPCs proliferation,
      differentiation, adhesion and migration.

PMID- 19388543
TI  - [Clinical significance of some genetic polymorphisms of cytochrome P-450: family
      CYP1 and subfamilies CYP2A, CYP2B and CYP2C].
AB  - The essence of pharmacogenetic studies is to provide a scientific explanation for
      personal differences in the process of drugs metabolism. Polymorphism of drugs
      biotransformation is clinically significant from the point of view of the
      effectiveness and safety of pharmacotherapy and an increased risk of some
      illnesses. The paper presents molecular mechanisms and clinical implication of
      several genetic polymorphisms of cytochrome P-450 (CYP) xenobiotics metabolizing
      enzymes and genetic predisposition to the occurrence of some diseases.

PMID- 19388544
TI  - [Fractalkine--structure, functions and biological activity].
AB  - Although chemokines, as chemotactic factors, were already known in 70's of the
      past century, it was only the progress in molecular biology, genetics and
      immunology which occurred in the past few years that opened the way to discover
      new molecules, their chemical structure and biological functions. Fkn
      (fractalkine, CX3CL1) is a unique chemokine and the only representative of CX3C
      group. It exists as a membrane-bound and soluble form. It interacts with cells
      expressing CX3CR1, a G-coupled protein receptor. The polymorphism of CX3CR1 gene
      modulates Fkn affinity to its receptror, which influences the risk of development
      and progression of various diseases. Its unique character is determined by its
      functions. Fkn is not only a chemotactic factor, but it also participates in
      leukocyte trafficking, adhesion and cytotoxic activities, modulates expression of
      cytokines, adhesion molecules, free oxygen radicals, iNOS and influences
      apoptosis. Its elucidation should not only help understanding of molecular events
      occurring in many autoimmune inflammatory, neoplasmatic diseases, but would allow
      to use Fkn, its receptor, or anti-Fkn antibodies in treatment of those diseases.

PMID- 19388546
TI  - [Stigma and related factors basing on mental illness stigma].
AB  - Stigmatization is a common problem to overcome for people suffering from chronic
      diseases. It usually follows infectious diseases, disabilities and mental
      disorders. In our study we explained basic concepts concerning stigma,
      particularly health-related one, and then we presented the most important socio
      demographic factors influencing attitudes towards mentally ill people
      exemplifying them by scientific literature on mental illness stigma. Profession,
      frequency of contact with mentally ill persons, level of mental health literacy,
      own experience, education level, culture-related factors, overall value
      orientation, gender and age are the most relevant factors which influence
      perception of people suffering from mental disorders. A review of surveys on
      dependencies between those factors and attitudes towards mentally ill people and
      tendencies to stigmatize with mental illness was presented. Mental health
      literacy is the most easily modifiable factor among all the presented here.
      Majority of campaigns concerning change of attitude towards mentally ill people
      consist in enhancement of mental health awareness in society.

PMID- 19388545
TI  - [The role of inhibins in functions and dysfunctions of female reproduction. Part
      I].
AB  - The regulation of reproduction is performed by complex hormonal system:
      hypothalamus--pituitary--ovary. There are a lot of ovarian peptides, playing an
      essential role in the regulation of this system. However, the mechanisms of their
      action are not exactly known. Inhibins are glycoproteins produced mainly in the
      ovaries and they take part in the regulation of menstrual cycle. They consist of
      glycosylated alpha subunit and one of two beta subunits, inhibin A and inhibin B.
      There are studies about possible use of inhibins in reproductive medicine. Recent
      data indicate the role of inhibin A in obstetrics. The measurement of inhibin B
      can provide useful information about ovarian reserve, and plays an important role
      in assisted reproductive techniques. Inhibin B can be also regarded as potential
      marker of diagnosis of premature ovarian failure (POF) and ovarian recovery in
      hypothalamic disturbances. Both inhibin A and inhibin B can play helpful role in
      the assessment of ovarian function in patient with Turner syndrome. The
      estimation of total inhibin levels in blood serum seems to be advantageous in the
      diagnosis of patients with polycystic ovary syndrome (PCOS) and ovarian tumors.
      There are requirements of further studies to clarify the use of inhibins in
      clinical practice of reproductive endocrinology.

PMID- 19388547
TI  - The amazing ear: what happens before the brainstem auditory evoked response.
AB  - The auditory mechanism is utilized by electroneurodiagnostic technologist to
      assess brainstem function for a variety of clinical purposes. Prior to the
      generation of the brainstem auditory evoked response (BAER) waveform, however a
      plethora of remarkable acoustical, mechanical, hydraulic, and electrical events
      occur at the outer ear; in the ear canal, in the middle ear cavity, and within
      the cochlea. This article will review and highlight the acoustic properties of
      the human ear the mechanical aspects of the middle ear the hydraulic events, and
      structural and electrical fine tuning of various aspects of the cochlear
      mechanism, as well as electrophysiological events generated by the ear.

PMID- 19388548
TI  - Transcranial Doppler series part II: performing a transcranial Doppler.
AB  - Because of its portability, low cost, and quick, noninvasive nature, transcranial
      Doppler (TCD) has become a widely utilized exam to evaluate the basal cerebral
      arteries for various disease processes. The test is considered a "blind" and very
      difficult study by most vascular labs. Neurologists commonly order TCD, so the
      performance of it is slowly being adopted by neurodiagnostic labs. To perform a
      quality TCD, the technologist must be extremely skilled. The technologist must
      know where to place and how to angle the probe in order to insonate the vessels
      and must be familiar with the TCD equipment. The technologist should also have an
      understanding of what each vessel's waveform should look like under normal
      circumstances.

PMID- 19388549
TI  - Standards and guidelines for the accreditation of educational programs in
      electroneurodiagnostic technology.

PMID- 19388550
TI  - Use and abuse of stat EEG.

PMID- 19388551
TI  - Emergency ("stat") EEG in the era of nonconvulsive status epilepticus.
AB  - The most widely accepted indication for a stat EEG (stEEG) is the suspicion of
      nonconvulsive status epilepticus (NCSE). NCSE has been reported with surprising
      frequency in a wide variety of acute structural and metabolic brain injuries and
      significantly increases the risk of permanent brain damage and death. This risk
      rises and the effectiveness of treatment decreases with delays in diagnosis and
      increased duration of NCSE. Recent evidence confirms that more than half of NCSE
      patients improve with anti-seizure treatment. The emergence of NCSE as a common,
      dangerous, time-urgent, and treatable problem has positioned it as a target for
      emergency therapeutic intervention. NCSE can only be diagnosed by EEG testing,
      and stEEG has demonstrated value in improving NCSE management. As a result, in
      the near future, EEG laboratories will see increasing demands for stEEG related
      to NCSE. The two main obstacles to an effective stEEG program are EEG
      technologist coverage and electroencephalographer availability after work hours.
      We recommend three simple but fundamental changes in the traditional approach to
      stEEGs in order to overcome these obstacles: the use of EEG set-up templates by
      onsite personnel, easy access to EEG instruments after hours, and remote stEEG
      connectivity for real-time, off-site electroencephalographer interpretation.

PMID- 19388552
TI  - Calculating frequency and duration in digital EEG.

PMID- 19388553
TI  - Waveform window #14. New sleep scoring.

PMID- 19388554
TI  - Microbe-induced epigenetic alterations in host cells: the coming era of patho
      epigenetics of microbial infections. A review.
AB  - It is well documented that the double-stranded DNA (dsDNA) genomes of certain
      viruses and the proviral genomes of retroviruses are regularly targeted by
      epigenetic regulatory mechanisms (DNA methylation, histone modifications, binding
      of regulatory proteins) in infected cells. In parallel, proteins encoded by viral
      genomes may affect the activity of a set of cellular promoters by interacting
      with the very same epigenetic regulatory machinery. This may result in epigenetic
      dysregulation and subsequent cellular dysfunctions that may manifest in or
      contribute to the development of pathological changes (e.g. initiation and
      progression of malignant neoplasms; immunodeficiency). Bacteria infecting mammals
      may cause diseases in a similar manner, by causing hypermethylation of key
      cellular promoters at CpG dinucleotides (promoter silencing, e.g. by
      Campylobacter rectus in the placenta or by Helicobacter pylori in gastric
      mucosa). I suggest that in addition to viruses and bacteria, other microparasites
      (protozoa) as well as macroparasites (helminths, arthropods, fungi) may induce
      pathological changes by epigenetic reprogramming of host cells they are
      interacting with. Elucidation of the epigenetic consequences of microbe-host
      interactions (the emerging new field of patho-epigenetics) may have important
      therapeutic implications because epigenetic processes can be reverted and
      elimination of microbes inducing patho-epigenetic changes may prevent disease
      development.

PMID- 19388555
TI  - Clinical microbiology of early-onset and late-onset neonatal sepsis, particularly
      among preterm babies.
AB  - Prematurity has got special challenge for clinicians and also other medical
      staff, such as microbiologists. Immature host defense mechanisms support early
      onset sepsis, which can be very serious with very high mortality. While the past
      decade has been marked by a significant decline in early-onset group B
      streptococcal (GBS) sepsis in both term and preterm neonates, the overall
      incidence of early-onset sepsis has not decreased in many centers, and several
      studies have found an increase in sepsis due to gram-negative organisms. With
      increasing survival of these more fastidious preterm infants, late-onset sepsis
      or specially nosocomial bloodstream infection (BSI) will continue to be a
      challenging complication that affects other morbidities, length of
      hospitalization, cost of care, and mortality rates. Especially the very low
      birthweight (VLBW) infants sensitive to serious systemic infection during their
      initial hospital stay. Sepsis caused by multiresistant organisms and Candida spp.
      are also increasing in incidence, has become the most common cause of death among
      preterm infants. This review focuses on the clinical microbiology of neonatal
      sepsis, particularly among preterm babies, summarizing the most frequent
      bacterial and fungal organisms causing perinatally acquired and also nosocomial
      sepsis.

PMID- 19388556
TI  - Broadening spectrum of bovine spongiform encephalopathies.
AB  - Until recently the etiology of bovine spongiform encephalopathy (BSE) was
      considered uniform. The infectious agent was thought to be a single strain of
      prion (posttranslationally altered form of normal prion protein: PrPSc) retaining
      its biochemical and biological characteristics during interspecies transmission.
      However, alternate PrPSc signatures through large-scale screening have recently
      been detected. In addition, genetic alterations governing susceptibility to prion
      infection and a mutation (E211K) capable of eliciting spontaneous BSE have been
      demonstrated. Thus, the spectrum of BSEs have broadened and three PrPSc variants
      (BSE-C, BSE-H and BSE-L) are now defined. Moreover, a new condition resembling
      BSE, idiopathic brainstem neuronal chromatolysis (IBNC), has been described that
      may also turn out to be a prion disease. Since one of the new BSE variants, L
      type BSE, proved highly pathogenic detection and further characterization of the
      new conditions are essential.

PMID- 19388557
TI  - Growth, keratinolytic proteinase activity and thermotolerance of dermatophytes
      associated with alopecia in Uyo, Nigeria.
AB  - Mycological research was conducted on the mycelial growth, keratinolytic
      proteinase activity and thermotolerance ofdermatophytes associated with alopecia
      patients in Uyo, Nigeria. The results revealed that Microsporum sp. - AP1,
      Epidermophyton sp. - AP2, Trichophyton rubrum - AP4, Trichophyton mentagrophytes 
      AP5 and a yeast Candida albicans - AP3 isolated exhibited variable growth and
      keratinase activity at different temperatures. Microsporum sp. - AP1 and T.
      mentagrophytes - AP5 survived heat treatment at 90 degrees C but exhibited best
      mycelial growth at 30 degrees C (with 53.41 mg/50 ml biomass dry weight) and 40
      degrees C (with 61.32 mg/50 ml biomass dry weight) respectively, after incubation
      for 2 weeks. Trichophyton rubrum - AP4 and Epidermophyton sp. - AP2 could not
      survive heat treatment at 90 degrees C but grew better at 40 degrees C (with
      38.52 mg/50 ml biomass dry weight) and 30 degrees C (with 48.32 mg/50 ml biomass
      dry weight) respectively, over the same incubation period, while C. albicans -
      AP3 grew better at 30 degrees C with 38.7 mg/50 ml biomass dry weight after 2
      weeks, but failed to survive at 70 degrees C. All the isolates except Candida
      albicans - AP3 survived at 80 degrees C and exhibited great potential to
      elaborate keratinolytic enzymes, with T. mentagrophytes demonstrating the best
      potential at 30 degrees C and 40 degrees C. Higher temperatures tended to reduce
      keratinolytic activities and there were significant (P < 0.05) relationships
      between biomass weight and enzyme productivities of all the isolates except T.
      mentagrophytes. This indicates that in some dermatophytes keratinolytic
      proteinase activity is not a function of cell multiplicity. This plus the high
      thermostability of the enzymes are important attributes in the consideration of
      preventive and therapeutic methods against dermatophytes in the tropics.

PMID- 19388558
TI  - Heat resistance of dermatophyte's conidiospores from athletes kits stored in
      Nigerian University Sport's Center.
AB  - The incidence and heat resistance of conidiospores produced by dermatophytes
      isolated from athlete's kits (canvasses, stockings and spike shoes) stored in
      Nigerian University Sport's Centre were investigated. Epidermophyton floccosum,
      Microsporum oudouinii, Microsporum canis, Trichophyton concentricum, Trichophyton
      mentagrophytes and Trichophyton rubrum were isolated and their incidence on the
      athlete's kits varied with the species and type of kits. Among the isolates T.
      mentagrophytes, T. rubrum and E. floccosum with 25%, 23% and 20% prevalence rates
      respectively, were the most common isolates, and are often associated with tinea
      pedis (athletes foot). Canvasses with the highest incidence of dermatophytes (25
      out of 34 fungal isolates) were the most contaminated kits and could serve as
      effective articles for the transmission of tinea pedis among athletes in Nigeria.
      The common etiological agents screened, produced asexual spores (conidiospores)
      that exhibited high resistance to heat treatment at 80 degrees C. Of the three
      isolates, E. floccosum, with a decimal reduction time (D-value) of D80 = 4.4 min
      was the most resistant followed by T. mentagrophytes with D80 = 4.0 min and then
      T. rubrum with D80 = 3.2 min. The spores elimination pattern indicates that
      increasing the heating duration would decrease the decimal reduction time and
      possibly denature the fungal propagules but may damage the skin during treatment
      with hot water compresses. The findings have shown that the use of hot water
      compresses is palliative but heat treatment especially vapour-heat treatment
      offers adequate preventive measures if applied for periodic treatment of
      contaminated kits. However, determining the correct condition for effective
      decontamination will require detailed understanding of the heat resistance of
      fungal spores. Otherwise treatment of kits with detergent and chaotropic agent
      such as urea and guanidinium salt is preferred to heat treatment.

PMID- 19388559
TI  - Review of meningococcal infection in children at a United Kingdom hospital.
AB  - Sixty-nine children were identified and evaluable. Forty-one (60%) presented with
      hypotension and/or abnormal neurological signs. In 34 (49%) a petechial rash was
      present on admission. Of note, 13 (19%) had a non-petechial rash, and rash was
      absent in 19 (28%). Twenty-one (30%) presented with meningism or meningitis. In
      one child the illness was so mild that the child was discharged prior to making a
      diagnosis. Five children died (7%). Sixty-three cases (91%) were diagnosed by
      blood or cerebrospinal fluid culture; these investigations remain the mainstay of
      diagnosis.

PMID- 19388560
TI  - The prevalence of extended-spectrum beta-lactamase-producing Escherichia coli and
      Klebsiella pneumoniae among clinical isolates from a general hospital in Iran.
AB  - This study was conducted at a 900+ bed general teaching hospital, from May to
      September 2007, in Iran. The aim of this study was to determine the prevalence of
      extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella
      pneumoniae and their antimicrobial pattern. The Kirby-Bauer disk diffusion method
      and the phenotypic disk confirmatory test were performed for each isolate. The
      total of 206 isolates including 106 E. coli and 100 K. pneumoniae were collected
      of which 122 isolates (59.2%) were ESBL positive. The prevalence of ESBL
      producing strains was 59.2% (122/206). All the isolates were susceptible to
      imipenem. Among the ESBL-producing isolates, the sensitivity was from 3.3% to
      61.5% for ampicillin to aztreonam. From female isolates (136), 59.5% and from
      male isolates (70), 58.6% were ESBL-producers. Ratios of isolates from
      hospitalized patients to out-patients were 94/28 in the ESBL-producing group. The
      number of ESBL-producing isolates according to the isolation sites showed a
      significant difference between ESBL-producers and non-producers in blood samples
      (P < 0.05). This study shows that the prevalence of ESBL strains in Iran is high.
      It seems necessary for clinicians and medical community personnel to be fully
      aware of ESBL-producing microorganisms.

PMID- 19388561
TI  - Biotransformation of L-tyrosine to tyramine by the growing cells of Lactococcus
      lactis.
AB  - The potential of pyridoxal-5-phosphate dependent tyrosine decarboxylase (E.C.
      4.1.1.25) of Lactococcus lactis was explored for the biotransformation of L
      tyrosine to tyramine. Maximum bioconversion of L-tyrosine to tyramine was
      achieved in tyramine production medium (pH -5.5) at 30 degrees C after 16 h of
      incubation with 0.2% L-tyrosine. The yield oftyramine was found to be 11.8
      microg/mL by the growing cells of L. lactis at shake flask level. Growth medium
      and different physico-chemical parameters to maximize the biotransformation of L
      tyrosine to tyramine were optimized and yielded 1.9-fold increased synthesis of
      tyramine.

PMID- 19388562
TI  - [Surgical anatomy of the liver and liver resection. Brisbane 2000 Terminology].
AB  - The authors analyse the two major liver segmentations--the French and the
      American ones--that are different only of the left hemi liver level. The new
      liver segmentation, with obvious surgical implications, and the liver resection
      terminology both unanimously adopted in Brisbane 2000 are furthermore discussed.

PMID- 19388563
TI  - Wilkie syndrome. What is this?
AB  - Superior mesenteric artery syndrome is extremely rare and is characterized by
      postprandial epigastric pain, nausea, vomiting and loss of appetite, with
      subsequent weight loss, which aggravates the condition of the patients. The
      syndrome is caused by compression of the third part of the duodenum in the angle
      between the aorta and the superior mesenteric artery. This review updates
      etiology, epidemiology, diagnosis, treatment and outcome of the superior
      mesenteric artery syndrome. Superior mesenteric artery syndrome is clearly
      defined and frequently associated with a wide range of predisposing conditions
      and surgical procedures.

PMID- 19388564
TI  - Confocal laser endomicroscopy and ultrasound endoscopy during the same endoscopic
      session for diagnosis and staging of gastric neoplastic lesions.
AB  - INTRODUCTION: Confocal LASER endomicroscopy (CLE) is a newly developed endoscopic
      technique which allows subsurface in vivo histological assessment during ongoing
      endoscopy and targeted biopsies. Ultrasound endoscopy (EUS) is a useful tool in
      staging upper GI malignant lesions. We describe for the first time the use of
      both techniques during the same endoscopic session, in a pilot study, in order to
      increase the diagnostic yield of histological assessment and provide the staging
      of the gastric neoplastic lesions thus decreasing the time to therapeutic
      decision. AIMS & METHODS: CLE has been performed with the Pentax EG-3870CIK
      confocal endomicroscope after a 5 ml intravenous 10% fluorescein injection; EUS
      has been performed subsequently, during the same endoscopic Propofol sedation
      session, using a standard radial EUS-scope. RESULTS: Eleven patients have been
      investigated, 4 females, 7 males, mean age 59.7 +/- 12.3 years. The indication of
      CLE/EUS exploration was the presence of a gastric polypoid lesion in 37% of
      cases, atypical gastric ulcer in 27% of patients, gastric lymphoma 18%, suspicion
      of gastric cancer recurrence after resection 9% and infiltrating type gastric
      cancer 9%. Histological assessment after targeted biopsy has established the
      diagnosis of gastric adenocarcinoma in 55% of cases, gastric lymphoma in 18% of
      cases, gastric adenoma, gastric GIST and gastric foveolar hyperplasia in 9% of
      cases respectively. CLE has allowed targeted biopsies in 81.8% of cases. In 2
      patients - one case with suspected recurrent gastric cancer after surgery and one
      case of gastric lymphoma, CLE has indicated normal gastric mucosa. The EUS
      evaluation has shown TO lesion in two cases, T1 in 3 cases, T2 in 3 cases, T3 in
      one case. The EUS evaluation showed in one gastric lymphoma patient a lesion
      interesting the mucosa and submucosa with regional adenopathy and a submucosal
      lesion with regional adenopathy in the other gastric lymphoma case. The
      therapeutic decision was surgery in 73% of cases, chemotherapy and follow-up in
      18% of cases and follow-up in 9% of cases. No complications were registered
      during the CLE/EUS explorations. CONCLUSION: CLE and EUS can be successfully
      associated during the same endoscopic session, for upper GI neoplastic lesions
      allowing targeted biopsies for histological assessment and disease staging for
      optimal therapeutic decision.

PMID- 19388565
TI  - Complicated diverticular disease--our recent experience.
AB  - Diverticular disease is more frequently seen in our practice. The aim of this
      retrospective study was to evaluate our experience with complicated diverticular
      disease in our surgical emergency unit. Between 2004-2007 46 cases with
      complicated diverticular disease were registered in Surgical Emergency Clinical
      Hospital of Bucharest. A male preponderance (sex ratio M: F 1:1.4) and a medium
      age of 62.9 +/- 15 years were recorded. Perforation was the main complication
      encountered and sigmoid colon was the most frequent involved segment (71.7%).
      Diagnostic procedures relayed especially on CT-scan. Three cases were operated
      laparoscopically. Failure of conservative measures was the main cause for
      interventions. A Hartmann procedure was performed in 7 patients (15.2%). Global
      mortality was 8.1% (4 cases). There were no significant differences among the
      surgical procedures employed. Diverticular disease is more frequently encountered
      in our practice. CT-scan is the most efficient diagnostic tool but there are
      limitations. Conservative measures are not always successful and urgent operative
      treatment is the only choice. Hartmann procedure is still frequently employed in
      our practice.

PMID- 19388566
TI  - [The absence of haptic perception in laparoscopic cholecystectomy--risk factor
      for biliary lesions].
AB  - BACKGROUND: Bile duct injuries are the main serious technical complication of
      laparoscopic cholecystectomy (LC). Each lesion is peculiar in its features as
      well as the surgeon's reaction when face it. AIM: To reveal the place of the
      human error according to accepted principles of cognitive psychology, beside
      other risk-factors involved in biliary accidents during LC. METHOD: Retrospective
      study on 18 patients treated for severe biliary lesions during LC in 1st Surgical
      Clinic of "Sf. Spiridon" Hospital, Iasi, Romania, between March 1993 and March
      2008. According to Strasberg's classification the lesions were: type C (n=1; 3%),
      type D (n=13; 39.4%), type E1-2 (n=2; 6.1%) and type E5 (n=2; 6.1%). In the
      medical records we followed up the technical aspects of the procedure (section,
      dissection, clips) and the lesional and anatomic factors attended at the moment
      of LC. We also assessed the concerned surgeons experience based on the number of
      the LC at time of the biliary accident. RESULTS: In our experience (10046 LC) the
      incidence of the biliary injuries was 0.1% only. We met four lesional and/or
      anatomic factors (mean) on each case with biliary lesion. Only five cases (27.7%)
      were detected intraoperatively, but Spearman's correlation between time of
      detection and surgeons experience is insignificant. CONCLUSION: Our results,
      rounded with cognitive psychology data from literature, suggest the role of the
      absence of haptic perception during laparoscopic procedures, in the occurrence of
      some errors, even in circumstances with "perfect visibility".

PMID- 19388567
TI  - [Precocious diagnosis in children's intussusception--a necessity].
AB  - Intussusception is the most common cause of intestinal obstruction in children.
      Despite the fact that this is a frequent and well known disease, sometimes
      clinical presentation is various and difficult to interpret, which leads to delay
      in diagnosis and treatment. Late treatment will sometimes require intestinal
      resection, with high morbidity and mortality. There are no laboratory tests
      useful in diagnosis of intussusception. The only diagnosis tools are history,
      ultrasound and radiology. We retrospectively reviewed medical files of 30
      patients, admitted and treated for intussusception in Children Hospital Cluj
      Napoca and underline the importance of early diagnosis and treatment. There is a
      connection between onset of the disease, presentation, treatment (conservative or
      surgical), complications and hospital stay.

PMID- 19388568
TI  - [A study of the incidence and the specific risk factors for surgical site
      nosocomial infections].
AB  - The aim of our study is to estimate the incidence of surgical site nosocomial
      infections in a general surgery department and also to present the importance of
      the risk factors associated with these infections using the latest diagnostic
      protocols. MATERIAL AND METHOD: a retrospective analysis of 3038 surgical
      procedures performed between 2000-2002. We identified all the patients with
      surgical site nosocomial infection (SSI) mentioned in the observation sheet using
      NNISS/HELICS protocols to appreciate the risk for surgical site nosocomial
      infections. The results were compared to those published in the literature.
      RESULTS: we selected 198 cases (6,55%) with surgical site nosocomial infections
      of 3024 surgical patients (we excluded 14 cases): 41.4% of them were superficial
      infections, 49% profound infections, 7.1% organ-space infections and 2.5% with
      mixed nosocomial infections. We analysed the incidence depending on the risk
      factors and the type of surgical procedure, the agents involved in the
      development of the postoperative nosocomial infections, the germs concerned and
      their antibiotics resistance. CONCLUSIONS: the rates of different NNISS values
      after surgical procedures with nosocomial infections are analysed relative to the
      rates published by HELICS study for Romania and other European countries and it
      shows larger rates than the european average, maybe because our country has not
      started yet the HELICS protocol for SSI.

PMID- 19388569
TI  - [Early and prolonged peritoneal lavage with laparoscopy in severe acute
      pancreatitis].
AB  - OBJECTIVE: The evaluation of precocious and prolonged lavage and drainage by
      laparoscopic approach in the treatment of severe acute pancreatitis. MATERIAL AND
      METHOD: This therapeutic prospective study was conducted during 01.01.2006
      31.03.2008 on a sample consisting of 35 subjects with the severe acute
      pancreatitis has been divided into two lots. A lot is formed by 16 patients whom
      were applied the method mentioned ahead and in the B lot--19 patients, treated by
      conventional and known methods of treatment. The method proposed, completed about
      laparoscopic approach in a third day of admission, consists, after setting
      lesional balance, in lavage of peritoneal space and mounting two tubes drainage,
      one subhepatic space and the other in Douglas space. Post operator for 7 days
      performed peritoneal lavage discontinuous with physiological serum. For an
      accurate assessment may were determined serum and peritoneal concentrations of
      interleukin 6. RESULTS: The duration of organic disfunction was 8 days for A lot
      subjects and 17,7 days for B lot subjects. The complications occurred and the
      needs of surgical treatment was net disadvantage at the patients treated
      conventionally. The mortality at A lot was 12.5% (n=2) and at lot B 36.8% (n=7).
      The tardive mortality by sepsis was null at subjects with lavage and was 15,8%
      (n=3) at subjects without lavage. The precocious mortality was 12,5% (n=2) in the
      A lot and 21% (n=4) in the lot B. The average hospitalization was 25,8 days in
      subjects with peritoneal lavage and 35,8 days in those treated conservatively,
      the difference is statistically significant. The method has proved not generating
      of morbidity and supplementary mortality. Study of the variation of serum and
      peritoneal concentrations of interleukin 6 shows the modulator effect of the
      peritoneal lavage early and prolonged of the inflammatory response and offers an
      argument of the inefficiency of short peritoneal lavage. CONCLUSIONS: The data
      obtained indicate early and extended peritoneal lavage by laparoscopic method as
      a useful therapy in the management of severe acute pancreatitis.

PMID- 19388570
TI  - Transplantation of mesenchymal stem cells cultured on biomatrix support induces
      repairing of digestive tract defects, in animal model.
AB  - Transplanted mesenchymal stem cells (MSCs) appear to play a significant role in
      adult tissue repair. The aim of this research was to obtain MSCs enriched, three
      dimensional (3D) patches for transplant, and to test their ability to induce
      repair of iatrogenic digestive tract defects in rats. MSCs were obtained from
      human and rat bone marrow, cultured in vitro, and seeded in a collagen-agarose
      scaffold, where they showed enhanced viability and proliferation. The phenotype
      of the cultured cells was representative for MSCs (CD105+, CD90+, and CD34-, CD45
      , CD3-, CD14-). The 3D patch was obtained by laying the MSCs enriched collagen
      agarose scaffold on a human or swine aortic fragment. After excision of small
      portions of the rat digestive tract, the 3D patches were sutured at the edge of
      the defect using micro-surgical techniques. The rats were sacrificed at time
      points and the regeneration of the digestive wall was investigated by
      immunofluorescence, light and electron microscopy. The MSCs enriched 3D patches
      were biocompatible, biodegradable, and prompted the regeneration of the four
      layers of the stomach and intestine wall in rats. Human cells were identified in
      the rat regenerated digestive wall as a hallmark of the transplanted MSCs. For
      the first time we constructed 3D patches made of cultured bone marrow MSCs,
      embedded into a collagen-rich biomatrix, on vascular bio-material support, and
      transplanted them in order to repair iatrogenic digestive tract defects. The
      result was a complete repair with preservation of the four layered structure of
      the digestive wall.

PMID- 19388571
TI  - Gas-chamber mediastinoscopy for dissection of the upper esophagus.
AB  - AIM: Mediastinoscopy has the potential to bring under view the upper mediastinum,
      the area most difficult to dissect during transhiatal esophagectomy. The aim of
      the present study was to evaluate in an animal model the feasibility of the gas
      chamber mediastinoscopy technique for dissection of the upper esophagus. METHODS:
      Operations were performed in nine Landrace pigs using a 30 degrees laparoscope
      and conventional 35-cm laparoscopic instruments. Through a left collar incision a
      virtual space was created with sharp and blunt dissection around the cervical
      esophagus and insufflated with CO2 at a pressure of 5 mmHg. Using one 10-mm
      optical trocar and two 5-mm working trocars dissection advanced in the
      periesophageal space with the aim to reach at least to the tracheal bifurcation.
      RESULTS: Performed under visual control, the procedure was accurate and safe, the
      level of tracheal bifurcation being reached in all cases. Anatomical structures
      such as trachea and its bifurcation, pleura, pericardium, arch of the azygos vein
      and periesophageal lymph nodes were visible during the operation. There were no
      major intraoperative incidents and blood loss was minimal. CONCLUSIONS: The
      technique of gas-chamber mediastinoscopy is feasible. It allows a fair amount of
      freedom of movement for the working instruments and offers a good view on the
      operative field for a controlled and accurate dissection. Further evaluation in
      experimental and clinical studies is required to establish the role of this
      procedure in esophageal surgery.

PMID- 19388572
TI  - Glasgow coma scale and APACHE II system data--are they normally distributed?
AB  - OBJECTIVE: To verify whether the Glasgow Coma Scale (GCS) and APACHE II system
      scores are normally distributed. METHOD: Medical records of seventy four head
      injured patients were reviewed. GCS and APACHE II data were compared to a
      standard normal distribution. The chi2 goodness of fit test, the one sample
      Kolmogorov-Smirnov test, the Lilliefors test, the Shapiro-Wilk test, and
      calculation of skewness and kurtosis were performed. Frequency histograms and
      normal probability plots were also constructed. RESULTS: GCS data were not found
      to be normally distributed with a Kolmogorov-Smirnov statistic of 3.181
      (p=0.000). In contrast, APACHE II data presented a normal distribution with a
      Kolmogorov-Smirnov statistic of 0.704 (p=0.704). CONCLUSIONS: We demonstrated
      that GCS data do not follow the normal distribution, and thus nonparametric tests
      should be employed when dealing with such data. Furthermore, APACHE II data
      follow the normal distribution, and parametric tests could be considered, even
      though nonparametric tests are still preferred.

PMID- 19388573
TI  - [Laparoscopic sleeve gastrectomy for morbid obesity].

PMID- 19388574
TI  - [Current consideration about obturator hernias in a personal case treated with
      herniotomy. 1928].

PMID- 19388575
TI  - [Subconjunctival nodule with Dirofilaria repens].
AB  - Dirofilaria repens infection, a zoonotic illness, is rarely seen in humans; it is
      more frequently met over the endemic areas of the Southern Europe and Sri Lanka.
      The authors report a case of dirofilaria conjunctivae in a 27 year old woman from
      Craiova; such infections are hardly to be found in our country. Our patient
      presented a mobile, bulbar, subconjunctival tumoral formation which was
      surgically removed; immature Dirofilaria repens was revealed into it. Case
      particularity was that the patient had not visited any of the endemic areas.
      Environmental changes with global warming can lead to some new unspecific
      diseases in our country.

PMID- 19388576
TI  - [Cystic meningioma].
AB  - Cystic meningioma represent a rare entity, accounting 1.7 to 11.7% from the total
      intracranial meningiomas. We present a 41 years old patients' case who suffered
      of an progressive bilateral visual acuity decreasing, more pronounced on the
      right side. The clinical examination revealed a severe reduction of vision,
      represented by difficulties in light perception on the right side. The MRI and CT
      scan showed an expansive, multi-lobular, fronto temporal process on the right
      side (87/58/63 mm), presenting a liquid signal, different from intra-cerebro
      spinal fluid, without contrast enhancement at the level of the septae. The
      patient is operated on, the total resection of an polycystic and spongious tumour
      being accomplished together with the aspiration of the liquid from the giant
      peritumoral cyst. The postoperative evolution was favourable. The anatomo
      pathological result: meningothelial meningioma. Several classifications, the
      etiology of intra and peritumoral cysts formation are discussed together with the
      therapeutical possibilities.

PMID- 19388577
TI  - [Late pancreatic metastasis from primary Grawitz tumor--surgical management].
AB  - Renal cell carcinoma (Grawitz tumor) is an epithelial tumor able, to develop, in
      some cases, very late metastases. The most frequent localization are: lung, bones
      and liver. Pancreatic metastasis are rare and appear late, sometime even after 12
      years from primary renal tumor. In this cases the differential diagnosis must be
      made with primary pancreatic tumors. We present a case report of pancreatic
      metastatic tumor developed 5 years after right nephrectomy for renal cell
      carcinoma. We decide to perform cephalic duodenopancreatectomy (Wipple type).

PMID- 19388578
TI  - Enterovirus detection in stool specimen: relevance for poliovirus and enterovirus
      surveillance.
AB  - Detection of enterovirus genome by PCR in clinical samples is now extensively
      used for the diagnostic of enterovirus infections given its rapidity and high
      sensitivity. In contrast, its use in surveillance programs targeting specific
      enterovirus serotypes remains less frequent. The most sensitive protocols are
      those amplifying in the 5'untranslated region (5'UTR). However the possibility to
      use sequence analysis of the 5'UTR amplicons for serotype identification is not
      yet well established. In this report, stool samples from polio suspected cases
      and their healthy contacts were tested. The results of direct detection of
      enterovirus genome by PCR and serotype identification based on sequence analysis
      of the PCR products in the 5'UTR were compared to those of standard cell-culture
      based protocols. Standard protocols detected enterovirus isolates in 7.4% of
      cases while 9.8% of samples were positive by PCR. Serotype identification based
      on sequence analysis of amplicons showed concordant results with serotypes
      determined on virus isolates by seroneutralisation or sequencing in the VP1 gene
      in 39% of cases only. These results confirm that the use of PCR amplification
      from stool samples improves the sensitivity of enterovirus detection but do not
      recommend the use of sequence analysis of the 5'UTR PCR product to determine
      enterovirus serotype.

PMID- 19388579
TI  - Phenotypic and molecular epidemiology of Acinetobacter baumannii strains isolated
      in Rabta Hospital, Tunisia.
AB  - Acinetobacter baumannii (A. baumannii) is often implicated in hospital outbreaks
      in Tunisia. It's a significant opportunistic pathogen that is usually associated
      with serious underlying diseases such as pneumoniae, meningitis and urinary tract
      infections. The aim of this prospective study was to evaluate the global state of
      its endemicity and the antibiotic resistance evolution. The possibility of
      nosocomial transmission of one or more epidemic strain(s) was investigated by
      means of 3 methods: biotyping, antibiotyping and Random Amplified Polymorphic DNA
      analysis (RAPD). MIC for imipenem by Ellipsometer-test strip (E-TEST). The
      presence of metallo-beta-lactamases (MBL) was detected according to the double
      synergy test of EDTA and imipenem disks. A. baumannii strains were mainly
      localized in intensive care (52.2%) and surgery units (23.6%). Among 224 strains
      that were studied, 4 biotypes were delineated with a predominance of biotype1.
      Resistance to beta-lactams was mostly associated with the production of
      cephalosporinases and penicilinases (84.3%). 45% of strains were resistant to
      imipenem which were associated with MBL production. RAPD gave 5 genomic groups.
      This study demonstrates the epidemic behaviour airborne spread of A. baumannii in
      hospital wards. The multiresistance was often responsible for failure of
      antibiotics therapy. The prevention of nosocomial infection and severe hygiene
      controls must be performed.

PMID- 19388580
TI  - A case control study to assess risk factors for hepatitis C among a general
      population in a highly endemic area of northwest Tunisia.
AB  - A matched case-control study was undertaken in 2004 in Beja, north-western
      Tunisia, to evaluate potential risk factors for hepatitis C infection. Cases were
      anti-HCV positive subjects screened in 1996 serosurvey. HCV seronegative controls
      (5 per case) were selected in the proximity of cases and matched for age and
      gender. A standardized questionnaire was used to collect demographic,
      socioeconomic, social behavior, medical and surgical history information. Matched
      odds ratios (OR) and adjusted OR (AOR) and their 95% CI were calculated in
      multivariate analysis using logistic regression. 57 HCV positive cases (mean age
      61.63 +/- 14,84; 68.4 % female) and 285 HCV negative controls (mean age 60.95 +/-
      14.66; 68.4 % female) were enrolled. Multivariate analysis revealed that
      intravenous drug injections (AOR=1.96; 95%CI[1.02-3.8] p=0.045), past history of
      invasive procedures (AOR=2.53; 95%CI[1.21-5.29] p=0.0014) and medical history of
      hypertension (AOR=2.31; 95%CI [1.17-4.56]p=0.015) were significantly associated
      to HCV infection. These results suggest that nosocomial transmission of HCV
      infection in north-west Tunisia is common.

PMID- 19388581
TI  - [Snake venom disintegrins: classification and therapeutic potential].
AB  - Biochemistry and pharmacology of snake venoms reveal structural and functional
      polymorphisms of proteins they contain. These lead their effects by their
      enzymatic activities (proteases, phospholipases A2, L-amino acid oxydases...) or
      by binding to membrane receptors. Disintegrin from snake venoms play a role as
      antagonists of cell adhesion and migration by binding integrins and blocking
      their function. Characterization of integrin antagonists from snake venom allows
      us understanding the function of some integrins providing new information to
      develop new therapeutic agents. In this review, we report classification and
      therapeutic implications of disintegrins. In particular the structural and the
      functional characteristics of lebestatin; a short disintegrin isolated from
      Tunisian Macrovipera lebetina snake venom.

PMID- 19388582
TI  - [Modulation of skeletal muscle contraction by the non-toxic fraction of Buthus
      occitanus tunetanus venom via the cholinergic receptors].
AB  - Cholinergic receptors have an essential physiological role in the central nervous
      system because of their implication in higher functions in the neuromuscular
      junction within the brain and also in the peripheral nervous system by activating
      nicotinic (nAChRs) or muscarinic (mAChRs) receptors. Moreover, cholinergic
      receptors could be recognized by animal toxins isolated from snake venoms or
      alkaloids having animal or vegetal origin. In this context, we aim to find such
      molecules in a non toxic venom fraction of Buthus occitanus tunetanus scorpion,
      M1, which could therefore constitute promising medical tool. We present here a
      physiological study in skeletal muscle cells that regroups data that have been
      recently published and some new results reinforcing the last ones. The global
      effect of M1, was firstly studied on isolated nerve-muscle preparation. In
      cultured myotubes, we have found that the intracellular calcium increase, induced
      by M1 was blocked when ryanodine or inositol 1,4,5-triphosphate receptors are
      inhibited. Moreover, we have shown that M1 application on myotubes, induced a
      membrane depolarization as seen with acetylcholine. The treatment of myotubes
      with alpha-bungarotoxin blocked in most parts the depolarization amplitude. Thus,
      these results confirm the presence of at least one component in M1 active in
      nAChRs.

PMID- 19388583
TI  - [Use of medicinal plants against scorpionic and ophidian venoms].
AB  - The scorpionic and ophidian envenomations are a serious public health problem in
      Tunisia especially in Southeastern regions. In these regions Artemisia campestris
      L is a plant well known which has a very important place in traditional medicine
      for its effectiveness against alleged venom of scorpions and snakes. In this
      work, we tested for the first time, the anti-venomous activity of Artemisia
      campestris L against the scorpion Androctonus australis garzonii and the viper
      Macrovipera lebetina venoms. Assays were conducted by fixing the dose of extract
      to3 mg/mouse while doses of venom are variable. The leaves of Artemisia
      campestris L were extracted by various organic solvents (Ether of oil, ethyl
      acetate, methanol and ethanol) and each extract was tested for its venom
      neutralizing capacity. For the ethanolic extract, a significant activity with
      respect to the venoms of scorpion Androctonus australis garzonii (Aag), was
      detected. Similarly, a significant neutralizing activity against the venom of a
      viper Macrovipera lebetina (Ml), was obtained with the dichloromethane extract.
      These results suggest the presence of two different type of chemical components
      in this plant: those neutralizing the venom of scorpion are soluble in ethanol
      whereas those neutralizing the venom of viper are soluble in dichloromethane.

PMID- 19388584
TI  - In silico investigation of intronless Rhodopsin-like G-protein coupled receptors
      (GPCR) in the human genome: features and classification.
AB  - The G-protein coupled receptors (GPCRs) form a large protein family in the human
      genome that have been widely studied and classified into classes and phylogenetic
      subfamilies. However, there still exist orphan GPCRs that are not classified in
      any of the known subfamilies and new bioinformatics approaches are still needed
      to address this issue. One of the interesting features of GPCRs is that a large
      proportion of these proteins are encoded by intronless genes. In this work, we
      are interested in the study of Rhodpsin-like GPCRs proteins encoded by this kind
      of genes. After a manual validation of their gene structure, we studied some of
      their properties including the number of exons, chromosomal location and protein
      length. The same trend was found for intronless GPCRs as compared to total GPCRs,
      particularly the uneven chromosomal distribution with a large number (one third)
      of GPCRs on chromosomes 1 and 11. The proportion of intronless GPCRs among all
      Rhdopsin-like GPCRs was estimated to about 26% which is significantly less than
      previously reported. Significant differences in protein length were found between
      subfamilies. We then used composition properties of DNA and protein sequences to
      classify intronless Rhodopsin-like GPCRs. Principal component analysis was used
      to identify key variable and then a discriminant analysis was used to compute
      discriminant functions that best separates the phylogenetic subfamilies. We found
      that the most important features to separates the groups is the proportion of
      aromatic amino acids in protein sequence and the contrast between (A+T) versus
      (G+C) in coding sequence. These functions are finally used to classify fourteen
      putative or unclassified GPCRs.

PMID- 19388585
TI  - [Mutation spectrum of Gaucher disease in Tunisia: high frequency of N370S/Rec
      NciI compound heterozygous].
AB  - Gaucher disease is the most common lysosomal storage disorder, it results from
      the inherited deficiency of the enzyme glucocerebrosidase, the accumulation of
      its substrate causes many clinical manifestations. Since the discovery of GBA
      gene, more than 200 different mutations have been identified, but only handful
      mutations are recurrent (N370S, L444P and c.84insG). In order to determine the
      mutation spectrum in Tunisia, we performed recurrent mutation screening in ten
      unrelated Tunisian children with Gaucher disease. Screening of recurrent mutation
      by PCR/RFLP and direct sequencing, has shown that N370S is the most frequent
      mutation (6/20 mutant alleles, 30%), followed by recombinant allele (RecNciI)
      which is found in five patients (5/20 mutant alleles, 25%), the L444P mutation
      represent 20% (4/20 mutant alleles). Our findings revealed that five among ten
      studied patients, were compound heterozygous N370S/RecNciI (50%). The screening
      of these mutations provides a simple tool for molecular diagnosis of Gaucher
      disease in Tunisian patients and allows also genetic counselling for their family
      members.

PMID- 19388586
TI  - [Consequences of insulin resistance on lipid profile in type2 diabetics group:
      study of 118 cases].
AB  - Insulin is a hormone which has an essential role in lipids metabolism by
      modulating the activity of many key enzymes and by its intervention on the
      production and the catabolism of lipoproteins. The aim of this study was to
      determine the influence of insulin resistance on lipid profile in a diabetic
      group. The study group consists of 118 diabetic patients. We assayed for each
      patient total cholesterol, high density lipoprotein cholesterol, triglycerides
      and insulin. Insulin resistance was determined by HOMA index. Insulin was found
      correlated to body mass index, triglycerides, waist circumference, and glycated
      haemoglobin. Triglycerides and glycated haemoglobin were significantly more
      elevated in insulin resistant group than in insulin sensitive group. Insulin
      resistance may be the initial anomaly in type 2 diabetes and incite us to search
      on molecular anomalies in the insulin action.

PMID- 19388587
TI  - Assessment of disinfectants cleaning against bacterial biofilm of house hold
      water tanks.
AB  - The purpose of this study was to compare the efficacy, in terms of bacterial
      biofilm penetration and killing, of some chemical disinfectants against E. coli
      and P. aeruginosa. This study was undertaken to examine the efficacy of some
      disinfectants including sodium hypochlorite, povidine and tryad detergent against
      E. coli biofilms and the efficacy of sodium hypochlorite and tryad detergents
      against P. aeruginosa. Two species biofilm of E. coli and P. aeruginosa were
      grown by flowing a dilute tryptic soy broth medium over an inclined cement,
      polyethylene, fiberglass and galvanized steel slides, 2.25 x 2.25 cm2 for 15
      days. Biofilm formation was evaluated by scanning electron microscopy (SEM) and
      standard plate counts procedures through selective media for both E. coli and P.
      aeruginosa. In addition, some disinfectants were selected through disk diffusion
      susceptibility test. The disinfectants which gave higher zone of inhibitions,
      were applied to remove of E. coli and P. aeruginosa biofilms from cement,
      fiberglass, polyethylene and galvanized steel slide surfaces. Results showed that
      all disinfectants tested gave high inhibition of biofilm adhesion to tank
      surfaces with some being significant. CONCLUSION: polyethylene and galvanized
      steel are strongly recommended as alternative drinking house holds water tanks in
      Saudi Arabia. The choice of disinfectants or cleaning agents along with optimum
      concentrations and the time of action is very important when destroying microbes.
      It is also important that resistance of microbes to some disinfectants and
      cleaning agents is take into consideration when planning the cleaning process.

PMID- 19388588
TI  - Regulating the human tissue trade.

PMID- 19388589
TI  - A civil litigator's guide to discovery obligations in the context of electronic
      medical records.

PMID- 19388590
TI  - No relaxing for relators: Stringent pleading requirements result in frequent
      dismissal of FCA claims for off-label marketing.

PMID- 19388591
TI  - [Charles Nicolle's theory on the natural history of infectious diseases].

PMID- 19388592
TI  - [Anti-citrullinated peptide antibodies: novel markers for rheumatoid
      polyarthritis].
AB  - Rheumatoid arthritis is a multi-factorial autoimmune disease in which patho
      physiological mechanisms have been partially elucidated these past few years.
      These recent advances have led to new and effective treatments that must be
      started early in the course of the disease. This review focuses on new
      serological markers, the anti citrullinated peptides antibodies which seem to be
      useful in early diagnosis and prognosis of rheumatoid arthritis and probably
      provide new insights in its pathogenesis.

PMID- 19388593
TI  - Novel mutations in LAMA2 gene responsible for a severe phenotype of congenital
      muscular dystrophy in two Tunisian families.
AB  - Congenital muscular dystrophies are a group of common genetically determined
      disorders often transmitted with a recessive mode of inheritance. In recent
      years, several deficiencies of proteins from the muscle membrane, extra cellular
      matrix, sarcomere, muscle cytosol and the nucleus have been described to cause
      CMD. The occidental type of CMD (MDC1A) in which the primary defect is a
      deficiency in laminin alpha2 chain (merosin) encoded by LAMA2 gene, accounts for
      30-40% of cases. The clinical course of CMD with complete laminin alpha2 chain
      deficiency may be variable but most often; severe forms characterized by
      hypotonia at birth, profound muscle weakness, marked delay in motor milestones
      are observed. Since the identification of the first LAMA2 gene mutations leading
      to merosin deficiency in 1995, several mutations have subsequently been reported
      in many exons of this gene without any "hotspot" region. In this work, we report
      two novel homozygous mutations c.8005delT and c.8244+1G>A in the LAMA2 gene in
      four Tunisian patients with a severe MDC1A phenotype belonging to two unrelated
      consanguineous families.

PMID- 19388594
TI  - [Complement protein hereditary deficits during purulent meningitis: study of 61
      adult Tunisian patients].
AB  - Sixty one Tunisian adult patients with bacterial meningitis were screened for
      complement deficiency. Functional activity of the classical and the alternative
      pathways of complement (CH50 and AP50 respectively) were measured according to
      standard haemolytic procedures. Serum concentrations of C3 and C4 were determined
      by nephelometry. Late complement component (C5-C9) and properdin concentrations
      were assessed by double-ligand EISA. Complement deficiency was found in eight
      patients (13%): Seven had late complement component deficiency (three C7
      deficiency, two C5 deficiency, one C6 deficiency and one C8 deficiency) and one
      had partial properdin deficiency. Patients with late complement component
      deficiency had a mean age of 24 years (range 17-32 years). All deficient patients
      had meningococcal meningitis. Recurrent meningitis was reported in half of the
      patients. Our findings demonstrated a high prevalence of complement deficiency in
      Tunisia suggesting that screening for hereditary complement deficiency should be
      performed in case of bacterial meningitides and meningococcal disease patients.

PMID- 19388595
TI  - [RT-PCR use for the diagnostic of chronic myeloid leukaemia].
AB  - The molecular analysis of chromosomal abnormalities associated with hematological
      malignancies allowed the identification of genes involved in theses
      rearrangements as well as of some recurrent mechanisms. Polymerase chain reaction
      (PCR) tools are now available to detect these rearrangements, allowing a better
      follow-up of these diseases. Chronic myeloid leukemia is a myeloproliferative
      disorder characterized by a reciprocal translocation t(9;22)(q34;q11) which
      results in a bcr-abl fusion gene. Retro-transcription polymerase chain reaction
      (RT-PCR) is used to detect bcr-abl to establish diagnosis and to monitor
      patients. We report here the results of 30 patients samples tested in the
      hematology laboratory at Pasteur Institute, diagnosed as chronic myeloid leukemia
      and monitored with RT-PCR. Our results highlight the interest of molecular tools
      to diagnose and monitor patients mainly when cytogenetic techniques are
      irrelevant such as cases with complex chromosomal rearrangements or when patients
      achieve Philadelphia negativity after treatment.

PMID- 19388596
TI  - [Detection of EBV by PCR in fresh and paraffin embedded samples of cavum tumour].
AB  - The nasopharyngeal carcinoma (NPC) is frequent in Tunisia. It's the second ORL
      cancer of men after the larynx one. To analyse the NPC characteristics in our
      population, we determined the frequency of EBV infection in 47 paraffin-embedded
      and 6 fresh NPC biopsies. We first extracted the DNA from tumoral tissus and then
      amplified viral sequences by PCR to detect and to type the infecting virus (EBV-A
      or ABV-B). Our results showed that amplifiable DNA has been obtained from 34/47
      paraffin-embedded NPC biopsies while 13/47 of the others biopsies contained
      degraded and not amplifiable DNA. All the fresh biopsies allowed to obtain DNA
      with good quality. The EBV infection frequency in paraffin-embedded NPC biopsies
      is 35% while EBV is detected in all fresh biopsies (6/6). Our analyse also showed
      that the EBV-A is predominant in our population compared to EBV-B as it was shown
      in most countries of the world. This study clearly shows that PCR results
      obtained with paraffin-embedded NPC biopsies are divergeant from those obtained
      with fresh biopsies. Because of DNA degradation in paraffin-embedded NPC
      biopsies, the biology molecular results from that kind of samples is criticable.
      Moreover the results obtained from fresh NPC biopsies confirmed the quasi
      constant association of EBV with undifferenciated carcinoma nasopharyngeal type.

PMID- 19388597
TI  - [Cytology and immunophenotyping of acute promyelocytary leukaemia].
AB  - Acute promyelocytic leukaemia (AML3) is characterized by particular clinical and
      biological features. We report the cytology and the immunophenotype of 14 AML3
      from which 3 were AML3v. A double negativity of HLA-DR and CD34 is found in 12
      cases and aberrant expression of CD2 in 2AML3v. Aberrant expression of CD56 and
      CD22 was shown in, respectively, one case, CD15, CD65 and CD117 expressions were
      variable. Cytological diagnosis is often evident, although in some cases, it is
      not typical and immunophenotype will contribute to the diagnosis.

PMID- 19388598
TI  - Involvement of the interdomain hydrophobic linker and the C-terminal helices in
      self-association of the molecular chaperone HSC70.
AB  - HSP70 from bacteria to man are known to self-associate to form multiple species
      suggesting that self-association is related to function. In order to determine
      the structural basis of HSP70 oligomerization, deletion mutants in the C-terminal
      domain of HSC70, a constitutive member of the HSP70 family, have been constructed
      and analyzed for their self-association properties by gel electrophoresis, size
      exclusion chromatography and analytical ultracentrifugation. The results of this
      investigation indicate that, whereas deletion of the GGMP rich C-terminal
      extremity of HSC70, containing EEVD motif stabilizes the oligomeric species,
      deletions of either the aD-aE C-terminal helices or the inter-domain hydrophobic
      linker contribute to the stabilization of the monomeric form. Thus, two non
      contiguous regions, located at both ends of the C-terminal domain of the protein,
      appear to form the contact interface in the oligomers and may interact in a
      dynamic fashion leading to the formation of several coexisting species.

PMID- 19388599
TI  - [Enzymatic synthesis of homogenous triacylglycerol in media without solvent].
AB  - The study of triacylglycerols synthesis using 1,3-regiospecific immobilized
      Rhizomucor miehei lipase (lipozyme) or non-regiospecific immobilized Candida
      antarctica lipase (novozyme) as biocatalyst was carried out in pure substrates
      conditions. Our results show that long-chain triacylglycerols were synthesized
      from glycerol and free fatty acids at a higher rate than medium-chain
      triacylglycerols which were themselves synthesized at a higher rate than short
      chain ones. Furthermore, it is clearly shown that linoleic acid is more slowly
      esterifled than oleic acid which is itself more slowly esterified than
      octadecanoic acid. The higher the number of unsaturation, the lower the rate of
      synthesis and the final yield. On the other hand, the final yield of synthesis is
      comparable when using specific or non-specific lipase, as biocatalyst.

PMID- 19388600
TI  - [Cyanobacteria and their toxic potential in dam water content in Northern
      Tunisia].
AB  - In order to get data about toxic cyanobacteria and their potential sanitary risk
      in 12 waterbodies situated in the north of Tunisia, some taxonomic, ecological
      and toxicological studies were undertaken since 2001. This paper provides the
      first screening of the potential toxic species of cyanobacteria as well as their
      geographical distribution. The microscopic examination of the phytoplankton
      samples show 42 species of cyanobacteria; 9 are frequently quoted by the
      literature as being potentially toxic. Among the inventoried cyanobacteria genera
      there are Pseudanabaena, Planktothrix Phormidium, Lyngbya, Microcystis,...
      Oscillatoria constitutes the most widespread one. The content of total
      microcystin (MCYST) was determined by protein phosphatase inhibition assays
      (PP2A). The total microcystin, detected in dissolved and particulate fractions in
      all the examined samples is generally low and varies between 2 and 7455 ng/l
      microcystin-LR equivalent per liter. The highest MCYST concentration is observed
      in autumn and generally in particulate MCYST concentrations.

PMID- 19388601
TI  - Mitochondrial 16S rDNA analysis of Tunisian androctonus species (Scorpions,
      Buthidae): phylogenetic approach.
AB  - Tunisian Androctonus species, for long time discussed, were recognized on the
      basis of mitochondrial 16S rDNA sequences. Although the analysed nucleotide
      sequence is rather short (about 300 bp), the obtained phlogenetic trees revealed
      that A. amoreuxi and A. aeneas form two well-supported sister clades against A.
      australis haplotypes. Each specimen of the very rare species A. aeneas showed a
      specific haplotype, but together formed a well-defined clade. Some A. amoreuxi
      specimens highlighted unidirectional mitochondrial introgression from
      neighbouring A. australis population. Within A. australis, previously described,
      subspecies subdivision (A. a .hector and A. a. garzonii) was not supported.

PMID- 19388602
TI  - Epidural granuloma arising from epidural catheter placement.
AB  - Indwelling epidural catheter placement for prolonged drug delivery or is
      commonplace. Epidural catheter placement leading to a subsequent epidural mass is
      infrequently symptomatic and thus not often sought after or uncovered. Such
      masses can mimic lesions causing tumor, infection, and inflammation, and when
      found, the etiology of granuloma formation is unclear. This article describes a
      case of a benign epidural granuloma masquerading as an epidural tumor thought to
      be caused by epidural catheter placement for postoperative total hip replacement
      pain control. After symptoms of mechanical and radiculopathic pain arose, the
      patient underwent an open biopsy, spinal decompression, and intradural
      exploration as an MRI evaluation identified a mass in the spinal canal.
      Pathologic examination identified a benign fibrous granuloma. At 36-month follow
      up, there was no evidence of symptom or tumor recurrence.

PMID- 19388603
TI  - An unusual case of polydactyly.
AB  - Polydactyly is defined as a congenital anomaly of the hand or foot with the
      presence of supernumerary digits. The frequency of polydactyly varies widely
      among populations. It can occur as an isolated condition or as a feature of a
      congenital condition. In the literature, the condition is commonly described in
      combination with an apparent congenital deformity. We describe a case of
      polydactyly with no other obvious, macroscopically visible anomaly. A 21-year-old
      man presented with a sprained left ankle. On examination, a slightly irregularly
      shaped fifth digit of the left foot that appeared like a tailor's bunion was
      observed. The patient reported slight weight-bearing pain and tenderness over the
      navicular bone. No fractures were seen on radiographs, but they revealed an os
      tibiale externum, an extra metatarsal bone conjoined distally with the fifth
      metatarsal, and an extra hypoplastic proximal phalanx. No obvious signs of
      deformity were present. A bunionette, which was an extra hypoplastic proximal
      phalanx, was observed at the base of the fifth toe. Few published reports have
      described isolated polymetatarsia, and none of those describe supernumeral
      digits. A comprehensive search of the literature found no cases identical to
      ours.

PMID- 19388604
TI  - Langerhans cell histiocytosis of the acetabulum in adults.
AB  - This article presents 2 uncommon cases of Langerhans cell histiocytosis of the
      acetabulum in adults. Langerhans cell histiocytosis is a benign lesion of bone
      with a diversity of radiographic appearances depending on location. Radiographs
      of our cases showed a clearly defined radiolucent area at the acetabulum.
      Magnetic resonance imaging revealed specific findings for Langerhans cell
      histiocytosis of the acetabulum. Gadolinium-enhanced images showed that abnormal
      signal was spread to the whole acetabulum surrounding the lesion. Orthopedic
      surgeons should be aware of the existence of this lesion and attentive to
      patients who report spontaneous hip pain, although Langerhans cell histiocytosis
      is a rare condition in adults. It is generally agreed that prognosis is more
      dependent on age at the time of diagnosis rather than on therapy. We recommend
      simple curettage for Langerhans cell histiocytosis of the acetabulum in adults to
      obtain a definite diagnosis and relieve pain.

PMID- 19388605
TI  - Two unusual cases of coronal lunate fracture.
AB  - Volar lunate fractures are rare injuries, usually seen as a result of high-energy
      trauma and often in association of other carpal injuries. We present 2 unusual
      cases of coronal volar lunate fractures. The first case involved a proximal pole
      scaphoid fracture in association with a volar lunate fracture. During surgical
      exposure, the lunate fracture was found to be rotated 180 degrees volarly. This
      displaced lunate fracture, although appearing small on radiographs, consisted of
      the entire volar half of the capitate facet of the distal lunate. Both the
      scaphoid and lunate fractures were anatomically reduced with fixation across the
      fractures. The second case was the result of a high-energy injury and included a
      transscaphoid, transtriquetral, translunate facture dislocation with a comminuted
      radial styloid fracture and a small ulnar styloid fracture. Operative reduction
      and internal fixation was performed of the scaphoid and lunate. The triquetral
      and comminuted radial styloid fractures were stabilized with K-wires. In both
      cases, following splinting and rehabilitation, an excellent functional outcome
      was obtained. Early recognition and operative treatment of these unusual lunate
      fractures in association with treatment of the concomitant injuries using an
      extended volar approach with open reduction internal fixation can lead to an
      excellent anatomic and functional outcome in these types of cases.

PMID- 19388606
TI  - Triple joint injuries of the same digit.
AB  - This article presents a rare case of simultaneous triple joint injuries in the
      same digit. A 54-year-old, right-handed man sustained simultaneous triple joint
      injuries in a digit, composed of a fracture of the dorsal base of the distal
      phalanx involving one-third of the phalanx, dorsal dislocation of the proximal
      interphalangeal joint with a volar plate fracture, and ulnal dislocation of the
      metacarpophalangeal joint. Surgery was performed on the patient. Two years
      postoperatively, active range of motion of the distal interphalangeal joint
      improved from 0 degrees to 40 degrees, of the proximal interphalangeal joint
      improved from -20 degrees to 100 degrees, and of the metacarpophalangeal joint
      improved from 5 degrees to 90 degrees. Grip strength was 32 kg compared to 35 kg
      on the nonaffected side. No ligamentous laxity was demonstrated in the finger
      joints. A fracture involving one-third of the phalanx may be caused by forced
      hyperextension of that joint. This hyperextension may result in a tear of the
      volar plate of the proximal interphalangeal joint, leading to a dislocation at
      that joint. This continuous force directs the metacarpophalangeal joint in a
      slight ulnal shift, and may result in rupture of the medial collateral ligament
      in the metacarpophalangeal joint. To our knowledge, this injury has not been
      reported in the literature.

PMID- 19388607
TI  - Chondromyxoid fibroma involving the metacarpophalangeal joint.
AB  - Chondromyxoid fibroma is a rare benign bony tumor classically occurring in the
      metaphyseal region of the long bones surrounding the knee, but also found with
      relative frequency in other long bones, the pelvis, ribs, and small foot bones.
      The small bones of the hand, however, are rarely involved. The tumor is
      considered a physeal plate remnant and may involve the epiphysis, diaphysis, or
      both along with its metaphyseal origin. It may cause cortical expansion and
      destruction, but consistently respects the periosteal boundary. We report a case
      of histopathologically confirmed chondromyxoid fibroma involving a metacarpal,
      proximal phalanx, and synovial tissues of the metacarpophalangeal joint. A 29
      year-old woman presented with pain, weakness, and a mass of the right ring finger
      metacarpophalangeal joint that had persisted since prior surgery to remove an
      extraosseous chondroma. Prominent soft tissue swelling and limited range of
      motion were noted, corresponding to magnetic resonance imaging findings of lytic
      changes in the right ring finger metacarpal and proximal phalanx, surrounded by
      an irregularly enhancing mass with soft tissue extension. Open biopsy revealed
      calcified cartilaginous synovial deposits suspicious for synovial chondromatosis,
      with erosion into surrounding bones. Histologic examination revealed an unusual
      chondromyxoid fibroma with joint involvement. The patient is >15 months out from
      synovectomy, intralesional curettage, and placement of demineralized bone matrix
      and allograft cancellous chips, and is without signs of recurrence. This benign,
      curable lesion should be included in the differential diagnosis of a bony lesion,
      even when a joint and adjacent bones are involved.

PMID- 19388608
TI  - Melorheostosis in the upper extremity.
AB  - Melorheostosis is a rare mesodermal disease affecting the skeleton and adjacent
      soft tissues. Often it is incidentally detected on radiographs. In the standard
      radiology and orthopedics literature, melorheostosis is described as a "flowing
      hyperostosis, resembling dripping candle wax as an incidental radiographic
      finding." A 22-year-old man presented with a 2-year history of right-hand pain.
      Radiologic evaluation of the hand showed massive sclerotic changes in the first
      and second metacarpal and phalangeal bones on the right side. Further
      radiographic evaluation of the right upper extremity revealed the same sclerotic
      changes in the right scapula, humerus, radius, and scaphoid. Computed tomography
      (CT) scans showed a high attenuation undulating cortical hyperostosis with a
      "dripping candle wax appearance" involving the radial and/or dorsal aspects of
      humerus, radius, scaphoid, and first and second ray bones of the hand.
      Radionuclide triphasic bone scintigraphy showed diffuse homogenous radiotracer
      uptake within the entire right upper extremity involving the scapula, humerus,
      radius, scaphoid, and first and second metacarpals and phalangeal bones of the
      hand. The patient was followed conservatively, and 1-year follow-up revealed no
      change in the clinical, laboratory, or radiological findings. The diagnosis of
      melorheostosis was made on the basis of the characteristic distribution,
      location, and combined radiographic, CT, and radionuclide imaging features of the
      abnormalities. Conservative treatment was recommended for the patient. After 26
      months of follow-up, despite the persistence of the radiologic findings, the
      patient is currently well, with no painful symptoms unless he performs forceful
      exercise.

PMID- 19388609
TI  - Tarsal coalition as a cause of failed tarsal tunnel release for tarsal tunnel
      syndrome.

PMID- 19388610
TI  - Lateral epicondylitis.

PMID- 19388611
TI  - Minimally invasive burst fracture fixation in the thoracolumbar region.
AB  - Minimally invasive spine surgery is evolving rapidly. Compared with the
      traditional posterior approach with long and wide exposure, the minimally
      invasive approach offers significant advantages in treating patients with spine
      trauma.

PMID- 19388612
TI  - Chondroitin sulfate in osteoarthritis therapy.
AB  - Despite the news of aid from chondroitin sulfate, recent research has questioned
      its efficacy in treating osteoarthritis.

PMID- 19388613
TI  - A low-profile method of hybrid tibial fixation for soft tissue grafts in anterior
      cruciate ligament reconstruction.
AB  - This article introduces a low-profile technique for anterior cruciate ligament
      reconstruction using an interference screw and knotless anchor. Biomechanically,
      this technique has a significantly greater load to failure than interference
      screw fixation alone.

PMID- 19388614
TI  - Femoral neck fractures: evidence versus beliefs about predictors of outcome.
AB  - It is unclear whether current practice reflects current evidence on predictors of
      clinically important outcomes like mortality and fixation failure. Knowledge of
      predictors of outcome can and should influence treatment decisions and can
      subsequently improve outcomes. We hypothesized that there is evidence about the
      significance of predictors of outcome not being considered in the decision making
      process in the treatment of hip fractures because many surgeons are unaware of
      it. We surveyed 298 North American and European orthopedic surgeons to examine
      their training and experience and their opinion on the relative importance of
      predictors of outcome of femoral neck fracture treatment. We compared the results
      with the highest level of therapeutic and prognostic evidence currently
      available. Surgeons' perceptions about the importance of the quality of fracture
      reduction, patient comorbidities, degree of fracture displacement, dementia, and
      prefracture walking ability were justified by the current literature. However, we
      further identified a number of variables deemed unimportant to surgeons that have
      evidence to support their use in managing patients with hip fractures, including
      the type of anesthesia as a modifiable variable. In contrast to surgeons'
      perceptions, the available evidence suggests regional anesthesia is associated
      with a lower mortality risk than general anesthesia.

PMID- 19388615
TI  - Subsidence of metal interbody cage after posterior lumbar interbody fusion with
      pedicle screw fixation.
AB  - Posterior lumbar interbody fusion is considered to be an excellent fusion
      procedure to stabilize anterior support, correct alignment in the sagittal and
      coronal plane, and achieve foraminal decompression by lifting the disk height.
      The metal interbody cage in posterior lumbar interbody fusion is thought to be
      useful to prevent collapse of the graft bone and to correct and maintain disk
      height; however, some studies have noted a gradual decrease of disk height due to
      cage subsidence. Therefore, to investigate the significance of cage subsidence,
      86 disk levels radiographically confirmed to have good union in 66 patients with
      posterior lumbar interbody fusion combined with pedicle screw fixation and a
      single metal cage for degenerative lumbar disease were retrospectively evaluated.
      The follow-up period ranged from 3 years to 10 years 3 months, with a mean of 7
      years 9 months. Cage subsidence often showed a gradual increase over time. At
      final follow-up, subsidence averaged 4.0 mm on the cranial surface and 2.7 mm on
      the caudal surface. Although the average increase of disk height was 3.2 mm
      immediately postoperatively, the final disk height decreased by 4.2 mm on average
      from that time. The degree of cage subsidence and decrease of disk height were
      not correlated with the final clinical results. Subsidence was not correlated
      with bone mineral density in the vertebral body, body weight, or site of the
      insertion. On the other hand, the wedge shape of the cage and the thickness of
      the resected endplate had a significant influence on cage subsidence.

PMID- 19388616
TI  - Lumbar degenerative scoliosis: outcomes of combined anterior and posterior pelvis
      surgery with minimum 2-year follow-up.
AB  - Combined anterior and posterior surgery is useful for fixed deformity of the
      lumbar spine. The specific indications for and clinical outcome parameters after
      combined surgery for patients with degenerative lumbar scoliosis have not been
      well defined. We retrospectively reviewed 14 consecutive patients with
      degenerative lumbar scoliosis treated with combined anterior and posterior
      arthrodesis with instrumentation to the pelvis. Mean patient age was 65 years
      (range, 49-88 years) and mean clinical follow-up was 44 months (range, 30-78
      months). Mean preoperative sagittal imbalance was 4.6 cm (range, 1.5-15.5 cm),
      which was maintained to 2.5 cm (range, 0.5-8 cm) at last follow-up. Mean
      preoperative Cobb angle of the major curve was 46 degrees (range, 20 degrees-67
      degrees), which improved to 6 degrees (range, 2 degrees-30 degrees) at last
      follow-up. The highest total postoperative scores were reported in patients with
      maximal correction of their curves at last follow-up. Correlation analysis of
      clinical outcome domains demonstrated that patient satisfaction with surgical
      management correlated strongly with domains of pain (r=0.86; P=.008) and weakly
      with domains of function (r=0.3; P=.02). Patients with degenerative lumbar
      scoliosis may be effectively treated with combined anterior and posterior surgery
      with instrumentation to the pelvis. Our results at a minimum of 2-year follow-up
      indicate that overall clinical outcomes are best in cases with maximal curve
      correction, and overall patient satisfaction with surgery is correlated with
      relief from pain.

PMID- 19388617
TI  - Surgical treatment of midclavicular fractures in the elderly: a comparison of
      locking and nonlocking plates.
AB  - Operative treatment of midclavicular fractures in patients older than 60 years
      poses an increased risk of fixation failure. Although plating of midclavicular
      fractures in the elderly is still a popular fixation method, osteopenic bone may
      result in plate loosening and fixation failure. The purpose of this study is to
      prospectively evaluate and compare the clinical outcomes of midclavicular
      fractures in patients older than 60 years who are treated with either a locking
      compression plate or nonlocking plate. Sixty-four elderly patients with
      midclavicular fractures were surgically treated with either a locking compression
      plate or nonlocking plate, which included dynamic compression plates and
      reconstruction plates. The locking compression plate group included 29 patients
      with an average age of 69.1 years. The nonlocking plate group included 35
      patients with an average age of 66.3 years. Both groups were similar for age,
      gender, injury mechanism, fracture patterns, and confounding medical condition
      (P>.5). However, the locking compression plate group had lower complication rates
      compared to the nonlocking plate group (P=.087). In addition, the locking
      compression plate group had higher rates of return to work and exercise (P=.02,
      P=.016, respectively). If surgery of elderly patients with midclavicular
      fractures is indicated, internal fixation with a locking compression plate is
      preferable to a nonlocking plate.

PMID- 19388618
TI  - Prevalence of cerebrovascular events during shoulder surgery and association with
      patient position.
AB  - The beach chair position is commonly used in both arthroscopic and open shoulder
      procedures. There has been recent concern that beach chair positioning may be an
      independent risk factor for intraoperative cerebrovascular insult, especially in
      concert with hypotensive anesthesia. We attempted to quantify the prevalence of
      intraoperative cerebrovascular events during shoulder surgery in the beach chair
      position. Two hundred and eighty-seven members of the American Shoulder and Elbow
      Surgeons (ASES) Society were e-mailed surveys, and 93 (32%) responded. The
      majority of these surgeons average >300 shoulder cases annually. Most of these
      cases are arthroscopic, and patient position is primarily beach chair. The total
      number of beach chair-position surgeries was estimated between 173,370 and
      209,628, and lateral decubitus-position surgeries were estimated between 64,597
      and 100,855. The overall rate of intraoperative cerebrovascular event was
      0.00291% (8/274,225). All cerebrovascular events were associated with surgeries
      in the beach chair position. The rate in the beach chair position ranged from
      0.00382% (8/209,628) to 0.00461% (8/173,370). If reported primary patient
      position was used > or = 75% of the time, no significant difference in observed
      cerebrovascular event rates was found between positions (P=.051-.0233). In
      relation to orthopedic procedures performed in the supine position, beach chair
      positioning does not appear to increase the risk of intraoperative
      cerebrovascular event.

PMID- 19388619
TI  - Unicompartmental knee arthroplasty compares favorably to total knee arthroplasty
      in the same patient.
AB  - There are several surgical management options for medial knee arthritis, and it
      is often difficult to decide whether a unicompartmental knee arthroplasty (UKA)
      or total knee arthroplasty (TKA) is appropriate. Few studies have compared UKAs
      and TKAs in the same patient. We identified 23 patients with osteoarthritis who
      had a TKA on one side and a UKA on the other. The preoperative values of the 2
      knees were not statistically different. Strict criteria were used to determine
      whether a UKA could be performed (functional anterior cruciate ligament, minimal
      deformity, and minimum changes in other compartments). Preoperative radiographs
      were reviewed to confirm that the knee undergoing TKA had medial compartment
      disease only. Knee Society scores, radiographic analysis, and patient preferences
      were recorded for all patients. Average follow-up was 46 months (range, 7.2-148
      months) and 42 months (range, 11.5-59.8 months) for TKA and UKA, respectively. We
      found little or no difference in outcomes between the 2 procedures, except for an
      improved range of motion with the UKA compared with the TKA (123 degrees +/-9
      degrees vs 119.8 degrees +/-7 degrees, respectively). Knee Society scores
      improved from 45.9 to 89.7 in UKA and from 42.4 to 90.3 in TKA. Of the 23
      patients, 11 expressed no preference between either knee and 12 preferred the
      unicompartmental knee; no patient preferred the total knee. With appropriate
      patient selection, UKAs are a successful option for patients with osteoarthritis.

PMID- 19388620
TI  - The influence of pain on knee motion in patients with osteoarthritis undergoing
      total knee arthroplasty.
AB  - Pain is the predominant symptom of degenerative knee arthritis and the main
      reason patients undergo total knee arthroplasty (TKA). Variation in patient
      response to pain has proved difficult to quantify. The effect of removing pain by
      testing TKA patients' range of motion (ROM) before and after the administration
      of anesthesia has not previously been analyzed. This study objectively quantifies
      the effect of eliminating pain on knee joint ROM for a typical group of TKA
      patients with osteoarthritis. We prospectively recruited 141 patients with
      osteoarthritis admitted for TKA to assess the inhibitory effect of pain on ROM.
      Passive maximum flexion, extension, and ROM were measured preoperatively before
      and after administration of anesthesia (spinal anesthetic followed by femoral and
      sciatic regional nerve blocks). Following pain abolition, passive maximum flexion
      increased by an average of 13.4 degrees (SD=11.9 degrees), passive maximum
      extension improved by an average of 3.0 degrees (SD=4.2 degrees), and passive ROM
      increased by an average of 16.4 degrees (SD=13.1 degrees). The change in each
      parameter was statistically significant (P<.0001). Improvements in flexion
      (P=.01) and ROM (P=.005) were significantly greater in women. Measurements taken
      before anesthesia reflect knee ROM that the patient will tolerate before pain
      becomes the limiting factor, while measurements taken after anesthesia is
      achieved suggest the knee ROM possible once pain is eliminated. Abolition of pain
      led to significant increases in knee flexion, extension, and ROM, suggesting that
      pain has a significant inhibitory effect on knee motion.

PMID- 19388621
TI  - Evaluation of success of a meniscus repair device for vertical unstable medial
      meniscus tears in ACL-reconstructed knees.
AB  - We retrospectively reviewed the success of meniscus repair with the FasT-Fix
      meniscus repair device for vertical unstable medial meniscus tears at the time of
      anterior cruciate ligament (ACL) reconstruction. A repair failure was defined as
      patients having medial knee symptoms leading to a subsequent arthroscopy
      confirming a tear at the repair site. Objective follow-up was obtained on 27
      patients at a mean of 3.1 years postoperatively (range, 2-5 years). Two of 22
      repairs (9%) in the red-red vascular zone and 4 of 5 repairs (80%) in the red
      white vascular zone retore at the repair site at an average of 9 months
      postoperatively (range, 3-20 months). The results of this study showed a high
      failure rate (22%) of unstable vertical medial meniscus repairs with ACL
      reconstruction, especially for repairs done to tears in the red-white vascular
      zone.

PMID- 19388622
TI  - On the importance of mentorship.

PMID- 19388623
TI  - Your diagnosis? Partial tear of the iliacus muscle.

PMID- 19388624
TI  - Double-shell giant vesicles mimicking Gram-negative cell wall behavior during
      dehydration.
AB  - A biomimetic system modeling the behavior of Gram-negative bacteria under
      hyperosmotic stress was developed. To this end, we introduced a two-step
      electroswelling procedure for encapsulation of giant unilamellar vesicles by an
      additional membrane. Both membranes of the resulting double-shell vesicles (DSVs)
      were fluid. Additionally, the outer membrane was rigidified by a monolayer of
      streptavidin forming a two-dimensional crystal. For strong attachment of this
      protein layer, the outer membrane contained biotinylated lipids. This reinforced
      protein-lipid compound membrane served to model the assembly of the murein wall
      and outer membrane of Gram-negative bacteria. We characterized DSVs by confocal
      laser scanning microscopy. Furthermore, DSVs were exposed to hyperosmotic media
      (osmotic difference 0-1100 mosm/L), and the resulting shapes were analyzed. DSVs
      coated with streptavidin were much less deformed or destroyed by osmotic stress
      than bare DSVs or DSVs coated with noncrystalline avidin. Osmotically stressed
      DSVs coated with streptavidin displayed weak wrinkling of the outer membrane and
      formed small daughter vesicles of the inner membrane. Both features and the
      toughness against hyperosmotic stress are well described characteristics of Gram
      negative bacteria.

PMID- 19388625
TI  - Structure of natural polyelectrolyte solutions: role of the
      hydrophilic/hydrophobic interaction balance.
AB  - A method allowing the evaluation of the solvophilic/solvophobic character of
      polyelectrolytes from their conformation in solution is discussed. Analyzed
      systems are salt-free aqueous solutions of natural copolysaccharides with
      controlled chemical structures. Small-angle X-ray scattering diagrams revealed
      their conformation by the "polyelectrolyte peak". The study of this peak allowed
      the determination of cb, the crossover concentration associated with the
      transition between the two structural organization regimes predicted by the
      scaling model of hydrophobic polyelectrolytes developed by Dobrynin and
      Rubinstein. A structural law of behavior as a function of the chain primary
      structure is built for chitosan, showing an increasing hydrophobic character when
      the fraction of N-acetyl-D-glucosamine residues (DA) increases. The results
      concerning this random copolymer are compared with those obtained for hyaluronan.
      Consistently, in the case of alginates, the relative content of the constitutive
      units is shown not to influence the polymer hydrophobicity.

PMID- 19388626
TI  - Structural mass spectrometry of the alpha beta-tubulin dimer supports a revised
      model of microtubule assembly.
AB  - The molecular basis of microtubule lattice instability derives from the
      hydrolysis of GTP to GDP in the lattice-bound state of alphabeta-tubulin. While
      this has been appreciated for many years, there is ongoing debate over the
      molecular basis of this instability and the possible role of altered nucleotide
      occupancy in the induction of a conformational change in tubulin. The debate has
      organized around seemingly contradictory models. The allosteric model invokes
      nucleotide-dependent states of curvature in the free tubulin dimer, such that
      hydrolysis leads to pronounced bending and thus disruption of the lattice. The
      more recent lattice model describes a predominant role for the lattice in
      straightening free dimers that are curved regardless of their nucleotide state.
      In this model, lattice-bound GTP-tubulin provides the necessary force to
      straighten an incoming dimer. Interestingly, there is evidence for both models.
      The enduring nature of this debate stems from a lack of high-resolution data on
      the free dimer. In this study, we have prepared alphabeta-tubulin samples at high
      dilution and characterized the nature of nucleotide-induced conformational
      stability using bottom-up hydrogen/deuterium exchange mass spectrometry (H/DX-MS)
      coupled with isothermal urea denaturation experiments. These experiments were
      accompanied by molecular dynamics simulations of the free dimer. We demonstrate
      an intermediate state unique to GDP-tubulin, suggestive of the curved colchicine
      stabilized structure at the intradimer interface but show that intradimer
      flexibility is an important property of the free dimer regardless of nucleotide
      occupancy. Our results indicate that the assembly properties of the free dimer
      may be better described on the basis of this flexibility. A blended model of
      assembly emerges in which free-dimer allosteric effects retain importance, in an
      assembly process dominated by lattice-induced effects.

PMID- 19388627
TI  - A diacetate ketone-catalyzed asymmetric epoxidation of olefins.
AB  - A fructose-derived diacetate ketone has been shown to be an effective catalyst
      for asymmetric epoxidation. High ee values have been obtained for a variety of
      trans and trisubstituted olefins including electron-deficient alpha,beta
      unsaturated esters as well as certain cis olefins.

PMID- 19388628
TI  - Temporal chemical shift correlations in reactions studied by hyperpolarized
      nuclear magnetic resonance.
AB  - High-resolution nuclear magnetic resonance spectroscopy (NMR) has the capability
      of providing often unrivaled detail on molecular structure and dynamics. Through
      hyperpolarization, a decisive gain in signal strength can be realized, which
      extends the applicability of NMR to the investigation of rapid processes far from
      equilibrium. The progress of irreversible chemical and biochemical reactions can
      be followed by hyperpolarized NMR with relative ease, within an observable window
      encompassing the subsecond to second time scales. Here, we present a scheme that
      uses real-time, hyperpolarization enhanced NMR to make temporal correlations
      accessible in addition to simply monitoring reaction progress. Since nuclear spin
      states can be preserved even if the spin carrying atoms directly participate in a
      reaction, it becomes possible to correlate the positions of these atoms between
      the reactant and the product species, over time. We demonstrate the application
      of this technique to the Grignard addition of methylmagnesium bromide to 3
      methylbenzophenone. The same experiment may be used for the determination of
      mechanisms and intermediate states in non-equilibrium processes in fields as
      varied as organic chemistry, enzymology, or protein folding.

PMID- 19388629
TI  - Evidence for relative radius of gyration as the criterion for selective diffusion
      behavior of polymer brushes.
AB  - When exposed to a dilute solution of free species, the polymer brush functions as
      a selective barrier to diffusion. Experiments with linear polymer chains and
      dendrimers of various sizes demonstrated that the selection criterion is relative
      size, i.e., radius of the free species (radius of gyration for linear chains and
      simple radius for dendrimers) relative to the radius of gyration of the chains
      composing the brush. This suggests that linear chains do not necessarily assume
      extended conformations as they diffuse into a brush but have conformations
      similar to those of nanoscale spherical inclusions.

PMID- 19388630
TI  - UV-driven reversible switching of a polystyrene/titania nanocomposite coating
      between superhydrophobicity and superhydrophilicity.
AB  - Hydrophilic titania (TiO(2)) nanoparticles were dispersed in solutions of
      polystyrene (PS), and the suspensions were cast on glass surfaces. The effect of
      drying temperature on the hydrophobic character of PS/TiO(2) was investigated:
      the static water contact angle increased with the drying temperature, and the as
      prepared coating could be adjusted from superhydrophilicity to
      superhydrophobicity just by controlling the drying temperature. Moreover, the
      superhydrophobic coating turning into a superhydrophilic one (CA < 5 degrees )
      after UV illumination, which can be recovered through being heated.

PMID- 19388632
TI  - What is inside a nonionic reverse micelle? Probing the interior of Igepal reverse
      micelles using decavanadate.
AB  - The interiors of reverse micelles formed using nonionic surfactants to sequester
      water droplets in a nonpolar environment have been investigated using the
      decavanadate molecule as a probe. Chemical shifts and line widths of the three
      characteristic signals in the 51V NMR spectrum of decavanadate, corresponding to
      vanadium atoms in equatorial peripheral, equatorial interior, and axial
      locations, measure the local proton concentration and characteristics of the
      reverse micellar interior near the decavandate probe. All samples investigated
      indicate deprotonation of the vanadate probe in the reverse micelle environment.
      However, the relative mobility of the decavanadate molecule depends on the
      reverse micellar components. Specifically, the 51V NMR signals of the decavandate
      in reverse micelles formed using only the Igepal CO-520 surfactant display sharp
      signals indicating that the decavandate molecule tumbles relatively freely while
      reverse micelles formed from a mixture of Igepal CO-610 and -430 present a more
      viscous environment for the decavanadate molecule; the nature of the interior of
      the nonionic reverse water pool varies significantly depending on the specific
      Igepal. The 51V NMR spectra also indicate that the interior core water pool of
      the reverse micelles is less acidic than the bulk aqueous solution from which the
      samples were created. Together, these data provide a description that allows for
      a comparison of the water pools in these different nonionic reverse micelles.

PMID- 19388631
TI  - Attenuated total reflection-FT-IR spectroscopic imaging of protein
      crystallization.
AB  - Protein crystallization is of strategic and commercial relevance in the post
      genomic era because of its pivotal role in structural proteomics projects.
      Although protein structures are crucial for understanding the function of
      proteins and to the success of rational drug design and other biotechnology
      applications, obtaining high quality crystals is a major bottleneck to progress.
      The major means of obtaining crystals is by massive-scale screening of a target
      protein solution with numerous crystallizing agents. However, when crystals
      appear in these screens, one cannot easily know if they are crystals of protein,
      salt, or any other molecule that happens to be present in the trials. We present
      here a method based on Attenuated Total Reflection (ATR)-FT-IR imaging that
      reliably identifies protein crystals through a combination of chemical
      specificity and the visualizing capability of this approach, thus solving a major
      hurdle in protein crystallization. ATR-FT-IR imaging was successfully applied to
      study the crystallization of thaumatin and lysozyme in a high-throughput manner,
      simultaneously from six different solutions. This approach is fast as it studies
      protein crystallization in situ and provides an opportunity to examine many
      different samples under a range of conditions.

PMID- 19388633
TI  - What is the structure of kaolinite? Reconciling theory and experiment.
AB  - Density functional modeling of the crystalline layered aluminosilicate mineral
      kaolinite is conducted, first to reconcile discrepancies in the literature
      regarding the exact geometry of the inner and inner surface hydroxyl groups, and
      second to investigate the performance of selected exchange-correlation
      functionals in providing accurate structural information. A detailed evaluation
      of published experimental and computational structures is given, highlighting
      disagreements in space groups, hydroxyl bond lengths, and bond angles. A major
      aim of this paper is to resolve these discrepancies through computations.
      Computed structures are compared via total energy calculations and validated
      against experimental structures by comparing computed neutron diffractograms, and
      a final assessment is performed using vibrational spectra from inelastic neutron
      scattering. The density functional modeling is carried out at a sufficiently high
      level of theory to provide accurate structure predictions while keeping
      computational requirements low enough to enable the use of the structures in
      large-scale calculations. It is found that the best functional to use for
      efficient density functional modeling of kaolinite using the DMol3 software
      package is the BLYP functional. The computed structure for kaolinite at 0 K has
      C1 symmetry, with the inner hydroxyl group angled slightly above the a,b plane
      and the inner surface hydroxyls aligned close to perpendicular to that plane.

PMID- 19388634
TI  - In situ transient spectroscopy for the study of glucuronidase activity within
      serum albumin.
AB  - Laser flash photolysis (LFP) has shown to be an efficient technique for in situ
      determination of the glucuronidase activity of human serum albumin (HSA). After
      incubation of the steroisomeric flurbiprofen glucuronides (FBPGluc) during
      regular time intervals at the selected temperatures, in the presence of protein,
      regression analysis was applied to the triplet decay at lambda=360 nm. This led
      to a satisfactory fitting when considering a set of four lifetimes; the
      corresponding preexponential coefficients AIFBP, AIIFBP, AFFBPGluc, and ABFBPGluc
      can be correlated with the presence of flurbiprofen (FBP) within the two known
      binding sites (I and II), together with FBPGluc free in solution (F) and bound
      (B) to the protein. The new methodology based on LFP of glucuronides in the
      presence of HSA is fast, experimentally straightforward, and does not involve any
      workup. This suggests the possibility of making use of the transient triplet
      triplet absorption for investigating the enzymatic-like activity of different
      host biomolecules and at the same time determining the distribution of the
      generated drug between several compartments in the protein.

PMID- 19388635
TI  - Influence of a triblock copolymer on phase behavior and shear-induced topologies
      of a surfactant lamellar phase.
AB  - The influence of a triblock copolymer, poly(ethylene oxide)20-b-poly(propylene
      oxide)70-b-poly(ethylene oxide)20 (Pluronic P123) on the phase behavior and on
      the shear-induced multilamellar vesicle (MLV, also called Onion) formation in the
      lyotropic lamellar phase of the nonionic surfactant C10E3 was investigated by
      means of rheology, small-angle neutron scattering (SANS), and microscopy. Added
      triblock copolymer shifted the Lalpha-L3 phase transition to lower temperatures.
      In the presence of triblock copolymer, MLV structure was not stable and easily
      transformed back into the lamellar phase with increasing polymer concentration
      and temperature. In the study of the shear-induced MLV formation, we found an
      increase of the critical shear rate for the onset of the shear-thickening, which
      also indicates the instability of MLV in the presence of the triblock copolymer.
      No MLV formation was observed at high polymer concentration. Suppression of the
      shear-induced MLV formation might be attributed to the enhancement of the
      effective surface tension originating from the excluded volume effect between
      polymers adsorbed onto the membranes.

PMID- 19388636
TI  - Nonlinear effect of GdnHCl on hydration dynamics of proteins: a 1H magnetic
      relaxation dispersion study.
AB  - Proton magnetic relaxation dispersion investigations with aqueous solutions of
      lysozyme and bovine serum albumin (BSA) in the 0-5 M range of guanidine
      hydrochloride (GdnHCl), pH 4.4, 27 degrees C, were taken up with the objective of
      examining the hydration dynamics of internal cavity waters as the protein is held
      under increasingly destabilizing conditions. Field cycling NMR and conventional
      pulsed NMR techniques were employed to cover a frequency range of 100 kHz to 50
      MHz. Analyses of dispersion profiles at different concentrations of GdnHCl were
      carried out considering the contributions from internal and surface waters. The
      denaturant-dependent variation of internal water contribution indicates that the
      reorientational disorder of internal waters decreases with increments of the
      denaturant up to its subdenaturing limit. For both proteins, the variation of
      effective correlation time with GdnHCl apparently shows a marginal shrink in
      hydrodynamic volumes under the subdenaturing condition. These results suggest
      that subdenaturing amounts of GdnHCl restrict the motional freedom of the
      internal waters, and can have considerable influence on the surface hydration. On
      increasing the denaturant concentration further, the dispersion amplitude drops
      sharply, indicating that the chaotropic action of the denaturant now runs over
      its own cavity water-ordering effect operative in the subdenaturing limit. The
      results are fundamentally important for the understanding of the susceptibility
      of protein structure and hydration to denaturants.

PMID- 19388637
TI  - Use of hydrazine in the hydrothermal synthesis of chalcogenides: the neutral
      framework material [Mn(2)SnS(4)(N(2)H(4))(2)].
AB  - The reaction system Mn/Sn/S/hydrazine/water at approximately 150 degrees C
      afforded [Mn(2)SnS(4)(N(2)H(4))(2)] (1). The compound has a unique neutral three
      dimensional framework with bridging hydrazine ligands and a variety of
      interconnectivity modes between MnL(6) (L = N, S) octahedra. The complex
      structure of 1 leads to strong antiferromagnetic interactions between the Mn(2+)
      centers and ordering at approximately 41 K. The stabilization of 1 underscores
      the high potential of hydrazine to promote the formation of novel chalcogenide
      materials under solvothermal conditions.

PMID- 19388638
TI  - Study of single protein adsorption onto monoamino oligoglycerol derivatives: a
      structure-activity relationship.
AB  - This paper describes a structure-property study of mixed self-assembled
      monolayers (SAMs) on gold that present methylated or hydroxyl-terminated
      polyglycerol (PG) structures that vary in size and architecture, and their
      ability to resist the adsorption of four test proteins from solution. Mixed SAMs
      were prepared by the reaction of an amine of the polyglycerol structures with a
      SAM that presents interchain anhydrides (the anhydride method). Surface plasmon
      resonance spectroscopy was used to measure the adsorption of fibrinogen,
      lysozyme, albumin, and pepsin to the resulting mixed PG amide/carboxylate
      terminated SAMs. In addition, FTIR infrared reflection-absorption spectroscopy
      (IRRAS) and contact angle goniometry were used to characterize the mixed SAMs.
      The study showed that even though methylation increases the hydrophobicity of
      these mixed PG SAMs, it greatly improved their ability to resist the adsorption
      of the test protein with the best performing surface demonstrating better
      resistance than a mixed SAM that presented poly(ethylene glycol) (PEG350). It was
      also shown that increasing the molecular weight of the PG structures (oligomer
      length or higher dendritic generations) generally resulted in decreased protein
      adsorption. With respect to the architecture, the linear oligoglycerols showed
      better resistance than their equal weight branched dendrons, while hyperbranched
      dendrons were more resistant to protein adsorption than perfect dendrons of equal
      weight.

PMID- 19388639
TI  - Evaluating the potential for enzymatic acrylamide mitigation in a range of food
      products using an asparaginase from Aspergillus oryzae.
AB  - Asparaginase, an enzyme that hydrolyzes asparagine to aspartic acid, presents a
      potentially very effective means for reducing acrylamide formation in foods via
      removal of the precursor, asparagine, from the primary ingredients. An
      extracellular asparaginase amenable to industrial production was cloned and
      expressed in Aspergillus oryzae . This asparaginase was tested in a range of food
      products, including semisweet biscuits, ginger biscuits, crisp bread, French
      fries, and sliced potato chips. In dough-based applications, addition of
      asparaginase resulted in reduction of acrylamide content in the final products of
      34-92%. Enzyme dose, dough resting time, and water content were identified as
      critical parameters. Treating French fries and sliced potato chips was more
      challenging as the solid nature of these whole-cut products limits enzyme
      substrate contact. However, by treating potato pieces with asparaginase after
      blanching, the acrylamide levels in French fries could be lowered by 60-85% and
      that in potato chips by up to 60%.

PMID- 19388640
TI  - Three-year comparison of the polyphenol contents and antioxidant capacities in
      organically and conventionally produced apples ( Malus domestica Bork. Cultivar
      'Golden Delicious').
AB  - The present study was performed to evaluate the polyphenol content and
      antioxidant capacity of apples (cv. ;Golden Delicious') grown under defined
      organic and conventional conditions. Apples were harvested at five comparable
      commercial farms over the course of three years (2004-2006). In 2005 and 2006 the
      antioxidant capacity was 15% higher (p < 0.05) in organically produced apples
      than in conventionally produced fruits. In 2005 significantly higher polyphenol
      concentrations were found in the organically grown apples. In 2004 and 2006 no
      significant differences were observed (2004, 304 +/- 68 microg/g organic vs 284
      +/- 69 microg/g conventional, p = 0.18; 2005, 302 +/- 58 micro/g organic vs 253
      +/- 41 microg/g conventional, p = 0.002; 2006, 402 +/- 100 microg/g organic vs
      365 +/- 58 microg/g conventional, p = 0.17). Year-to-year variations in the
      antioxidant capacity and the polyphenol content of up to 20% were more
      significant than the production method found within one year. Finally, flavanols
      and flavonols were major determinants of the antioxidant capacities in these
      apples. Overall, the production method had a smaller impact on the variation in
      the polyphenol content and antioxidant capacity of apples than the yearly
      climate.

PMID- 19388641
TI  - Anomalous photophysics of H1 antihistamines in aqueous solution.
AB  - Electronic absorption, emission, and excitation spectra, and fluorescence
      lifetimes of two H1 antihistamines--tripelennamine and mepyramine--are
      investigated in detail to ascertain their usefulness as fluorescent probes for
      ligand binding to G-protein coupled receptors. The photophysical behavior of
      these compounds in aqueous solution is complex due to the presence of three
      protonable nitrogens, intramolecular hydrogen bonding, quenching due to the
      formation of a charge transfer state, and intramolecular fluorescence resonance
      energy transfer. At physiological pH values, anomalous photophysical behavior is
      observed: the compounds are found to be in a ground-state equilibrium mixture of
      two species, one with the alkylamine tail involved in an intramolecular hydrogen
      bond and a second without such a bond. This internal hydrogen-bonded tail has a
      profound effect on the ground and excited-state properties of both tripelennamine
      and mepyramine, which is further elucidated by comparing them to the reference
      compounds 2-aminopyridine and 2-(N,N-dimethylamino)pyridine.

PMID- 19388642
TI  - Joint experimental-theoretical investigation of the lower bound states of the
      NO(X2Pi)-Kr complex.
AB  - We describe the first measurement of the near IR spectrum of the NO-Kr van der
      Waals complex. A variant of IR-REMPI double-resonance spectroscopy is employed in
      which the IR and UV lasers are scanned simultaneously in such a way that
      throughout the scan the sum of the two photon energies is kept constant, matching
      a UV resonance of the system. In the region of the first overtone vibration of
      the NO monomer, we observe several rotationally resolved bands for the NO-Kr
      complex. In addition to the origin band located at 3723.046 cm(-1), we observe
      excited as well as hot bands involving the excitation of one or two quanta of z
      axis rotation. Another band is assigned to the excitation of one quantum of
      bending vibration. The experimental spectra are compared with results of bound
      state calculations for a new set of potential energy surfaces calculated at the
      spin-restricted coupled cluster level. For the average vibration-rotation
      energies, there is excellent agreement between the theoretical results based on
      the coupled states (CS) approximation and the full close-coupling (CC) treatment.
      Finer details like the electrostatic splitting and the P-type doubling of the
      rotational levels are accounted for only within the CC formalism. The comparison
      of the CC results with the measured spectra confirms the high quality of the
      PESs. However, the high resolution of the experiments is sufficient to identify
      some inaccuracies in the difference between the potential energy surfaces of A'
      and A'' reflection symmetry.

PMID- 19388643
TI  - A three-dimensional porous metal-organic framework constructed from two
      dimensional sheets via interdigitation exhibiting dynamic features.
AB  - A three-dimensional porous metal-organic framework (PCN-18) was constructed
      through interdigitating two-dimensional grid sheets composed of 4,4'-(anthracene
      9,10-diyl)dibenzoate and copper paddlewheel secondary building units, and its
      dynamic features were evidenced by gas sorption isotherms.

PMID- 19388644
TI  - Zn(II)-PEG 300 globules as soft template for the synthesis of hexagonal ZnO
      micronuts by the hydrothermal reaction method.
AB  - Hexagonal ZnO micronuts (HZMNs) have been successfully synthesized with the
      assistance of poly(ethylene glycol) (PEG) 300 via a hydrothermal method. The
      structure and morphology of the HZMNs were characterized by X-ray powder
      diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), and selected area electron diffraction (SAED). An individual
      ZnO micronut is revealed as twinned crystals. Time-dependent investigation shows
      that the growth of HZMNs involves a dissolution-recrystallization process
      followed by Ostwald ripening, in which is the first formed solid ZnO particles
      dissolve and transform to HZMNs with hollow structure. PEG 300 has been found to
      play a crucial role in the growth of this unique hollow structure. TEM
      observations show that the PEG chains aggregate to globules in water, which then
      have interaction with the dissolved zinc species to form the globules in a coiled
      state under hydrothermal conditions. These Zn(II)-PEG 300 globules act as soft
      template for the growth of HZMNs, and the possible growth mechanism is proposed.
      The room-temperature photoluminescence (PL) spectrum shows red emission around
      612 nm with a full width at half-maximum (fwhm) only about 13 nm.

PMID- 19388645
TI  - Inhibition of subgenomic hepatitis C virus RNA replication by acridone
      derivatives: identification of an NS3 helicase inhibitor.
AB  - We report the synthesis and structure-activity relationship (SAR) of a large
      series of acridones and acridone-fragment derivatives designed on the basis of
      the selective antihepatitis C virus (HCV) activity shown by acridone 2,
      previously studied as a potential antibovine viral diarrhea virus (BVDV)
      compound. The evaluation of their ability to inhibit the HCV replication in Huh-5
      2 cells led to the identification of new, selective inhibitors. This indicates
      that the acridone skeleton, when properly functionalized, is a suitable scaffold
      to obtain potential anti-HCV agents. Interestingly, during identification of
      possible cellular and viral targets, it was discovered that compound 23 exerts
      inhibitory activity on the HCV NS3 helicase, a very promising target for the
      development of anti-HCV drugs.

PMID- 19388647
TI  - Synthesis and evaluation of a novel indoledione class of long chain fatty acid
      elongase 6 (ELOVL6) inhibitors.
AB  - Novel indoledione derivatives were synthesized and evaluated as long chain fatty
      acid elongase 6 (ELOVL6) inhibitors. Systematic optimization of an indole class
      of lead 1 led to the identification of potent ELOVL6 selective inhibitors.
      Representative inhibitor 37 showed sustained plasma exposure and good liver
      penetrability in mice. After oral administration, 37 potently inhibited ELOVL6
      activity in the liver in mice.

PMID- 19388648
TI  - Mapping proton wires in proteins: carbonic anhydrase and GFP chromophore
      biosynthesis.
AB  - We have developed an algorithm for mapping proton wires in proteins and applied
      it to the X-ray structures of human carbonic anhydrase II (CA-II), the green
      fluorescent protein (GFP), and some of their mutants. For both proteins, we find
      more extensive proton wires than typically reported. In CA-II the active site
      wire exits to the protein surface, and leads to Glu69 and Asp72, located on an
      electronegative patch on the rim of the active site cavity. One possible
      interpretation of this observation is that positively charged, protonated buffer
      molecules dock in that area, from which a proton is delivered to the active site
      when the enzyme works in the dehydration direction. In GFP we find a new internal
      proton wire, in addition to the previously reported wire involved in excited
      state proton transfer. The new wire is located on the other face of the
      chromophore, and we conjecture that it plays a role in chromophore biosynthesis
      that occurs following protein folding. In the last step of this process,
      transient carbanion formation was suggested to occur on the bridge carbon
      [Pouwels et al. Biochemistry 2008, 47, 10111]. Residues on the new wire (Thr62,
      His181, Arg96) may participate in proton abstraction from this bridge carbon
      atom. A possible mechanism involves a rotation of the Thr62 side chain and
      completion of a short wire by which the proton is transported to His181, while
      the negative charge is transferred to the imidazolone carbonyl, producing a
      homoenolate intermediate that is stabilized by Arg96. Finally, comparison of the
      proton wires in the two proteins reveals common motifs, such as short
      internalized Ser/Thr-Glu hydrogen-bonded pairs for ultrafast proton abstraction,
      and threonine side chain rotation functioning as a proton wire switch.

PMID- 19388649
TI  - A general screening strategy for peptide-based fluorogenic ligands: probes for
      dynamic studies of PDZ domain-mediated interactions.
AB  - A systematic and general approach for identifying efficient probes for class I
      PDZ domains based on environment-sensitive chromophores is presented. A series of
      peptides derived from the C-terminal sequence of Stargazin was first used with
      PDZ domains of PSD-95 and Shank3 to identify the optimal position and linker
      length for the 4-DMAP chromophore. The results were applied to well-characterized
      ligand sequences for each set of domains to generate high affinity probes that
      retain their native sequence specificity and yield remarkable fluorescence
      increases upon binding. These probes constitute efficient tools to study the
      dynamics and regulatory mechanisms of PDZ domain-mediated interactions.

PMID- 19388650
TI  - In situ controllable loading of ultrafine noble metal particles on titania.
AB  - Herein we present a novel and facile approach to controllably load ultrafine
      noble metal nanoparticles on titania through in situ redox reaction between the
      reductive titanium(III) oxide support and metal salt precursors in aqueous
      solution. A series of noble metal/TiO(2) nanocomposites with uniform metal
      dispersion, tunable metal particle size, and narrow metal particle size
      distribution were obtained.

PMID- 19388651
TI  - Ionization of N2O4 in contact with water: mechanism, time scales and atmospheric
      implications.
AB  - Ionization of N(2)O(4) in and on thin water films on surfaces is believed to be a
      key step in the hydrolysis of NO(2) which generates HONO, a significant precursor
      to the OH free radical in the lower atmosphere. Molecular dynamics simulations
      using "on the fly" high-level MP2 potentials are carried out for ONONO(2) x
      (H(2)O)(n) clusters, n < or = 8, used to mimic the surface reaction, in order to
      investigate the ionization process and determine its time-scale and mechanism
      around room temperature. The results are (i) the isolated molecule does not
      convert to the NO(+)NO(3)(-) ion pair, even for long times; (ii) for ONONO(2) x
      (H(2)O)(n) with n = 1 and 2, ionization takes place in several picoseconds; (iii)
      for n > or = 3, ionization is essentially immediate, implying that the neutral
      species does not have sufficient lifetime to be considered a significant
      intermediate in the reaction; and (iv) even at ice temperatures, T < or = 250 K,
      ionization for n > or = 3 is immediate. The implications for hydrolysis of oxides
      of nitrogen on surfaces in the atmosphere are discussed.

PMID- 19388652
TI  - Palladium-catalyzed asymmetric dearomatization of naphthalene derivatives.
AB  - An intramolecular enantioselective metal-catalyzed dearomatization reaction is
      described. This procedure allows the dearomatization of naphthalene derivatives
      through an electrophilic aromatic substitution-type reaction on a Pd(II)
      intermediate. The high yields and enantioselectivities achieved make this
      procedure a valuable method for synthetic chemists.

PMID- 19388653
TI  - Heterogeneous catalysis of a copper-coated atomic force microscopy tip for direct
      write click chemistry.
AB  - We report a constructive scanning probe lithography method that uses
      heterogeneous copper-coated atomic force microscopy tips to catalyze azide-alkyne
      cycloadditions (CuAAC) between solvated terminal alkyne molecules and azide
      terminated self-assembled monolayers on silicon surfaces. Spatially controlled
      surface functionalization was carried out successfully with 50 mM ethanolic
      solutions of small molecules bearing terminal alkyne groups--propargylamine, 4
      pentynoic acid, and an alkynyl-oligoethyleneoxide. We observed that reaction
      occurs only where the copper tip is in contact with an azide-terminated surface
      resulting in features with linewidths on the order of 50 nm. The extent of
      surface functionalization, as measured by changes in surface topography and
      lateral force microscopy, depends on the scanning force (31-350 nN) and scanning
      speed, with significant surface patterning observed even at speeds as high as 64
      microm/s. In contrast with related SPL techniques, this approach affords a direct
      write lithographic approach to constructively modifying and patterning surfaces
      at the nanoscale without the need for auxiliary reagents. All that is required is
      (1) an azide surface, (2) a solution of a terminal alkyne, and (3) a copper
      coated AFM tip. These advantages allow the direct attachment of a potentially
      limitless library of molecules that bear terminal alkyne functionalities,
      including biomolecules, under relatively mild conditions, with sub-100 nm spatial
      resolution.

PMID- 19388654
TI  - Synthetic, structural, and theoretical investigation of guanidinate complexes
      containing planar Cu(6) cores.
AB  - The addition of diethylcyanamide to a tetrahydrofuran solution of lithium
      dialkylamide LiN(CH(3))(2) or Li NCH(2)CH(2)CH(2) CH(2), Li(PYR), results in the
      corresponding lithium 1,1,3,3-tetraalkylguanidinate, Li(TAG). The subsequent
      metathesis reaction of Li(TAG) with CuCl generates hexanuclear copper(I)
      complexes with the general formula [Cu(mu-TAG)](6), where TAG = DEDMG (1) and
      DEPYRG (2).

PMID- 19388655
TI  - Effects of quantum delocalization on structural changes in Lennard-Jones
      clusters.
AB  - The ground states of Lennard-Jones clusters (LJ(n)) for sizes up to n = 147 are
      estimated as a function of the de Boer quantum delocalization length, Lambda,
      using the variational Gaussian wavepacket method. Consequently, the n-Lambda
      phase diagram is constructed showing the ranges of stability of various
      structural motifs, including the Mackay and anti-Mackay icosahedra, several
      nonicosahedral but highly symmetric structures, and liquidlike (or disordered)
      structures. The increase in Lambda favors more disordered and diffuse structures
      over more symmetric and compact ones, eventually making the liquidlike structures
      most energetically favorable.

PMID- 19388656
TI  - Use of 5,5-(dimethyl)-i-Pr-PHOX as a practical equivalent to t-Bu-PHOX in
      asymmetric catalysis.
AB  - The use of 5,5-(dimethyl)-i-Pr-PHOX as a practical equivalent of t-Bu-PHOX in
      asymmetric catalysis is reported. This new member of the phosphinooxazoline
      (PHOX) ligand family behaves similarly in terms of stereoinduction to t-Bu-PHOX
      with the key advantage of being readily accessible as both enantiomers starting
      from either (S)- or (R)-valine.

PMID- 19388657
TI  - Asymmetric phthalocyanine synthesis by ROMP-capture-release.
AB  - Statistical condensation of norbornenyl-tagged phthalonitrile 3 (Pn A) and 4,5-di
      4-methoxyphenoxyphthalonitrile 4 (Pn B) followed by ring-opening metathesis
      polymerization (ROMP) of Pcs AB(3) and B(4) produced asymmetric Pc-appended
      polymers. Acidic cleavage of the resulting polymers afforded 2,3,9,10,16,17-hexa
      (4-methoxyphenoxy)-23-hydroxy Pc 9. A more soluble 2,3,9,10,16,17-hexa-4
      pentylphenoxy-23-hydroxy Pc 13 was synthesized by the same strategy and modified
      with sebacoyl chloride demonstrating that the unmasked hydroxyl site is reactive
      as a nucleophile.

PMID- 19388658
TI  - Porous metal-organic frameworks based on an anthracene derivative: syntheses,
      structure analysis, and hydrogen sorption studies.
AB  - Solvothermal assembly of 5,5'-(9,10-anthracenediyl)di-isophthalate (H(4)adip)
      with in situ-generated dicopper and diiron paddlewheel secondary building units
      (SBUs) afforded two porous metal-organic frameworks (MOFs), designated as PCN-14
      and PCN-15, respectively. The two MOFs crystallize in different structures,
      characterized by a difference in the dihedral angles between the anthracene and
      the phenyl rings of the adip ligand. PCN-14 retains permanent porosity under
      dehydration and contains nanoscopic cages while PCN-15 contains only one
      dimensional hexagonal channels along the (0 0 1) direction which require solvent
      stabilization. The aromaticity of the anthracene rings of the adip ligand in
      conjunction with the nanoscopic cages grants PCN-14 high excess hydrogen
      adsorption capacity of 2.70 wt % at 77 K, 760 Torr (4.42 wt % at saturation), as
      well as high hydrogen affinity of 8.6 kJ/mol at low H(2) coverage. These values
      are compared to other tetracarboxylate-derived MOFs to better understand the role
      of the aromatic rings in hydrogen adsorption.

PMID- 19388659
TI  - Self-assembly of chemically engineered hydrophilic dextran into microscopic
      tubules.
AB  - Although macromolecular self-assemblies are mostly fabricated from amphiphilic
      copolymers, here we report a tubular structure self-assembled solely from
      hydrophilic dextran-derived homopolymers via electrostatic interaction. To obtain
      tubular structures, we prepared two oppositely charged dextran derivatives by
      incorporating 2-bromoethylamine (Dex-BH) and chloroacetic acid (Dex-CA) into
      dextran, and their structures were confirmed using Fourier transform infrared
      spectroscopy. The two oppositely charged dextran derivatives self-assembled into
      microsize tubules when mixed in a pH 4.0 buffer solution. The tubular self
      assemblies were sensitive to both pH and salt concentrations. Scanning electron
      microscopy and light microscopy confirmed that the tubules have hollow structures
      up to 100 microm long with a diameter between 600 nm and 2 microm. The X-ray
      study did not reveal any ordered molecular organization. This paper explores the
      mechanism of the tubule self-assembly and suggests a model.

PMID- 19388660
TI  - Bisnicalaterine A, a vobasine-vobasine bisindole alkaloid from Hunteria
      zeylanica.
AB  - A new bisindole alkaloid, bisnicalaterine A (1), consisting of two vobasine-type
      skeletons, and 3-epivobasinol (2) and 3-O-methylepivobasinol (3), with vobasine
      type skeletons, were isolated from the leaves of Hunteria zeylanica, and their
      structures were elucidated on the basis of spectroscopic data and chemical
      correlation. Bisnicalaterine A showed moderate cytotoxicity against various human
      cancer cell lines.

PMID- 19388662
TI  - Theoretical study of elementary steps in the reactions between aluminum and
      teflon fragments under combustive environments.
AB  - Gas-phase reactions between aluminum particles and Teflon fragments were studied
      to develop a fundamental understanding of the decomposition reactions and
      combustion processes of the Al-Teflon composites. The reactions were investigated
      theoretically using ab initio calculations at the MP2/aug-cc-pVDZ level, with the
      final thermokinetic data obtained with coupled cluster theory (CCSD(T)/aug-cc
      pVTZ). Among reactions under oxygen-lean conditions, CF(3) + Al --> CF(2) + AlF
      channel is the fastest, followed by the CF(2) + Al --> CF + AlF and CF + Al --> C
      + AlF channels. Under oxygen-rich conditions, reactions of COF with aluminum are
      probed to be faster than those involving COF(2) species. Reaction path
      multiplicity has been considered. Our results show that multiplicity plays a very
      important role in determining the reaction order, that is first order or addition
      elimination reactions of Al with CF(3) are predicted to be faster than those
      proceeding through direct abstraction or second order. In addition, the present
      kinetic model suggests that CF(3) + Al --> CF(2) + AlF with m = 1 and COF + Al -
      > CO + AlF channels are very competitive under the same thermal conditions. The
      computed enthalpies of reaction are systematically compared with the available
      literature. The predicted kinetic model and its time constants (tau) are in good
      qualitative agreement with experimental observations of the reactions between Al
      nanoparticles and Teflon for the 500-1200 K temperature range.

PMID- 19388661
TI  - The preparation of colloidally stable, water-soluble, biocompatible,
      semiconductor nanocrystals with a small hydrodynamic diameter.
AB  - We report a simple, economical method for generating water-soluble, biocompatible
      nanocrystals that are colloidally robust and have a small hydrodynamic diameter.
      The nanocrystal phase transfer technique utilizes a low molecular weight
      amphiphilic polymer that is formed via maleic anhydride coupling of poly(styrene
      co-maleic anhydride) with either ethanolamine or Jeffamine M-1000 polyetheramine.
      The polymer encapsulated water-soluble nanocrystals exhibit the same optical
      spectra as those formed initially in organic solvents, preserve photoluminescence
      intensities, are colloidally stable over a wide pH range (pH 3-13), have a small
      hydrodynamic diameter, and exhibit low levels of nonspecific binding to cells.

PMID- 19388664
TI  - Relocation of the distal histidine in cytochrome c peroxidase: properties of
      CcP(W51H), CcP(W51H/H52W), and CcP(W51H/H52L).
AB  - Many heme proteins have distal histidine residues that play important roles in
      determining heme protein reactivity. These distal histidines are in significantly
      different orientations,and distances from the heme iron in different heme
      proteins and the position of the distal histidine relative to the heme iron can
      influence reactivity at the heme center. To explore the effect of distal
      histidine position on the properties of cytochrome c peroxidase (CcP), three CcP
      mutants in which tryptophan 51 was replaced with a histidine residue were
      constructed. All three mutants, CcP(W51H), CcP(W51H/H52W), and CcP(W51H/H52L),
      have altered electronic absorption spectra, indicating that the heme group in the
      mutants is six-coordinate rather than five-coordinate as it is in wild-type CcP.
      The hydrogen peroxide reaction rate is 56-6200-fold slower for the mutants than
      for wild-type CcP. All three mutants form a CcP Compound I-like intermediate, in
      which the Fe(IV) site decays between 500 and 3000 times more rapidly than the
      Fe(IV) site in wild-type CcP Compound I. The W51H mutations have a weaker effect
      on cyanide binding, with the cyanide affinity only 2-8 times weaker than for CcP.
      The cyanide association rate constants are between 5 and 85 times slower for the
      W51H mutants, while the cyanide dissociation rate constants range from 3 times
      slower to 6 times faster than those of wild-type CcP.

PMID- 19388665
TI  - TGF-beta1 gene silencing for treating liver fibrosis.
AB  - Small interfering RNA (siRNA) and short hairpin RNA (shRNA) targeting different
      regions of transforming growth factor beta1 (TGF-beta1) mRNA were designed and
      the silencing effect was determined after transfection into immortalized rat
      liver stellate cells (HSC-T6). There was not only significant decrease in TGF
      beta1, tissue inhibitor of metalloproteinase 1 (TIMP-1), alpha-smooth muscle
      actin (alpha-SMA) and type I collagen after transfection with TGF-beta1 siRNAs,
      but also synergism in gene silencing when siRNAs targeting two different start
      sites were used as a pool for transfection. The two siRNA sequences which
      efficiently inhibited TGF-beta1 gene expression were converted to shRNAs via
      cloning into the pSilencer1.0. There was significant decrease in TGF-beta1 and
      TIMP-1 when HSC-T6 cells were transfected with pshRNA targeting the same regions
      of TGF-beta1 mRNA as siRNAs. Furthermore, TGF-beta1 gene silencing in HSC-T6
      cells significantly decreased the levels of inflammatory cytokines, such as tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta). In
      conclusion, both siRNA and shRNA showed sequence-specific and dose dependent TGF
      beta1 gene silencing and have the potential to treat liver fibrosis.

PMID- 19388666
TI  - Synthesis of nitric oxide by the NOS-like protein from deinococcus radiodurans: a
      direct role for tetrahydrofolate.
AB  - Genes encoding for proteins with high sequence homology to the heme-containing,
      oxygenase domain of mammalian nitric oxide synthase (NOS) have been identified in
      a number of bacteria. Many of these species of bacteria do not contain the genes
      that encode for the synthetic machinery to produce tetrahydrobiopterin (H(4)B), a
      cofactor of NOS required for NO synthesis. These bacteria have the genes for the
      synthesis of tetrahydrofolate (H(4)F) which contains the redox-active pteridine
      ring of H(4)B. These observations led us to investigate whether H(4)F could be
      used for the synthesis of NO by NOS-like enzymes from bacteria that cannot make
      H(4)B. The NOS gene from one such bacterium, Deinococcus radiodurans, was cloned
      and expressed (deiNOS) in Escherichia coli and then purified and characterized.
      The K(D) of deiNOS for the NOS substrate arginine (0.9 +/- 0.1 mM) drops by over
      2 orders of magnitude in the presence of H(4)F (7.4 +/- 0.1 microM). Further, NO
      is synthesized from the NOS substrate N-hydroxy-l-arginine (NHA) by deiNOS in the
      presence of H(4)F. Stopped-flow spectroscopic data reveal that H(4)F accelerates
      the rate of decay of the ferrous-oxy/ferric-superoxo species in substrate
      turnover. These data strongly suggest that H(4)F may be used by D. radiodurans to
      replace H(4)B as a redox-active cofactor for nitric oxide synthesis.

PMID- 19388668
TI  - Genetically encoded bioluminescent indicators for stress hormones.
AB  - This study demonstrates bioluminescent indicators for determining stress hormones
      in mammalian cells. A genetically encoded bioluminescent probe for stress sensing
      was first synthesized with a LXXLL motif-linked ligand binding domain of the
      glucocorticoid receptor (GR LBD), which was then sandwiched between the fragments
      of Gaussia luciferase (GLuc). This prototype of the bioluminescent indicators was
      carefully modified with a circular permutation (CP) and/or a corepressor motif.
      The first notable appearance by cofusion of a corepressor motif to the probe was
      the biphasic dose-response curves of the indicator to cortisol. A CP largely
      improved the detection limit of the indicator to cortisol up to 100 times.
      Fabrication of both CP and the attachment of a corepressor motif in the indicator
      synergistically contributes to (i) the lower detection limit and wider dynamic
      range and (ii) the enhanced absolute luminescence and ligand selectivity. This
      study is the first example that contribution of corepressor motifs to single
      chain probes was investigated. This study also provides new insight into
      improving the sensorial properties of single-chain probes with CP.

PMID- 19388667
TI  - Resonance Raman studies of the (His)(Cys)3 2Fe-2S cluster of MitoNEET: comparison
      to the (Cys)4 mutant and implications of the effects of pH on the labile metal
      center.
AB  - MitoNEET is a 2Fe-2S outer mitochondrial membrane protein that was initially
      identified as a target for anti-diabetic drugs. It exhibits a novel protein fold,
      and in contrast to other 2Fe-2S proteins such as Rieske proteins and ferredoxins,
      the metal clusters in the mitoNEET homodimer are each coordinated by one
      histidine residue and three cysteine residues. The interaction of the ligating
      His87 residue with the 2Fe-2S moiety is especially significant because previous
      studies have shown that replacement with Cys in the H87C mutant stabilizes the
      cluster against release. Here, we report the resonance Raman spectra of this
      naturally occurring Fe(2)S(2)(His)(Cys)(3) protein to assess local structural
      changes associated with cluster lability. Comparison of mitoNEET to its
      ferredoxin-like H87C mutant indicates that Raman peaks in the approximately 250
      300 cm(-1) region of mitoNEET are influenced by the Fe-His87 moiety. Systematic
      pH-dependent resonance Raman spectral changes were observed in this spectral
      region for native mitoNEET but not the H87C mutant. The approximately 250-300 cm(
      1) region of native mitoNEET is also sensitive to phosphate buffer. Thus,
      conditions that influence cluster release are shown here to concomitantly affect
      the resonance Raman spectrum in the region with Fe-His contribution. These
      results support the hypothesis that the Fe-N(His87) interaction is modulated
      within the physiological pH range, and this modulation may be critical to the
      function of mitoNEET.

PMID- 19388669
TI  - Increased throughput for low-abundance protein biomarker verification by liquid
      chromatography/tandem mass spectrometry.
AB  - Low-abundance protein quantification has historically been performed using ligand
      binding techniques. However, due to the time and cost associated with developing
      enzyme-linked immunosorbent assay (ELISA), mass spectrometric approaches are
      playing an increasingly important role. Protein quantification at or below the
      nanogram per milliliter level using liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) typically utilizes an immunoaffinity (IA) enrichment step
      such as immunoprecipitation. In order to maximize mass spectrometry (MS)
      sensitivity, protein enrichment is followed by a proteolytic cleavage step used
      to generate a surrogate peptide with better mass spectrometric properties. Unlike
      ELISA, IA-LC/MS/MS is a serial technique that can require up to 3 days for a
      single batch analysis due to lengthy incubation and digestion steps. This report
      describes the use of immunoprecipitation in 96-well ELISA format (IPE) and
      microwave-assisted protein digestion to reduce the time required to perform
      LC/MS/MS protein analyses to within a single day. The utility of this approach
      was investigated through its application to previously published LC/MS/MS protein
      assays from our laboratory for two cardiotoxicity biomarkers, Myl3 and NTproBNP.
      Using commercially available antibodies, IPE and microwave-assisted digestion
      were used to repeat intraday validations for these markers, and intraday
      precision (%CV) and accuracy (%RE) did not exceed 11% or 3% for either assay,
      respectively. Additionally, lower limits of quantification of 100 pg/mL
      (NTproBNP) and 0.95 ng/mL (Myl3) were achieved.

PMID- 19388670
TI  - Composition-tuned Co(n)Si nanowires: location-selective simultaneous growth along
      temperature gradient.
AB  - We report the simultaneous and selective synthesis of single-crystalline Co(n)Si
      NWs (n = 1-3) and their corresponding crystal structures--simple cubic (CoSi),
      orthorhombic (Co(2)Si), and face-centered cubic (Co(3)Si)--following a
      composition change. Co(n)Si NWs were synthesized by placing the sapphire
      substrates along a temperature gradient. The synthetic process is a successful
      demonstration of tuning the chemical composition in Co(n)Si NWs. The synthesis
      and detailed crystal structure of single-crystalline Co(2)Si and Co(3)Si are
      reported for the first time including the bulk and the nanostructure phases. The
      electrical and magnetic properties of Co(2)Si NWs are investigated and compared
      with those of CoSi NWs.

PMID- 19388671
TI  - Ultrafast nonlinear coherent vibrational sum-frequency spectroscopy methods to
      study thermal conductance of molecules at interfaces.
AB  - It is difficult to study molecules at surfaces or interfaces because the total
      number of molecules is small, and this is especially problematic in studies of
      interfacial molecular dynamics with high time resolution. Vibrational sum
      frequency generation (SFG) spectroscopy, where infrared (IR) and visible pulses
      are combined at an interface, has emerged as a powerful method to probe
      interfacial molecular dynamics. The nonlinear coherent nature of SFG helps
      overcome the sensitivity issues, especially when femtosecond IR pulses are used.
      With femtosecond pulses, a range of vibrational transitions can be probed
      simultaneously and high time resolution can be achieved. Ultrafast SFG
      experiments use three pulses, a pump pulse to generate nonequilibrium conditions
      with a pair of probe pulses, and two time delay parameters. Mapping SFG intensity
      as a function of the two time delays creates a two-dimensional surface, where one
      axis (t(1)) provides information about molecular dynamics driven by the pump
      pulses, and the other axis (t(2)) about the dynamics of the SFG probing process.
      We present examples of ultrafast SFG measurements drawn from our studies of heat
      transport through interfacial molecules that are models for molecular wires in
      electronic circuits. In these flash-heating experiments, a self-assembled
      monolayer (SAM) of long-chain molecules adsorbed on a metal surface is subjected
      to a large amplitude (up to 800 K) temperature jump. Specific vibrational
      reporter groups on the SAM molecules probed by SFG serve as tiny ultrafast
      thermometers approximately 1.5 A thick with a approximately 1 ps response time.
      These SFG thermometers can monitor ultrafast heat transport through the SAM
      molecules. By varying the lengths of the molecular wires we can tell if the heat
      is propagating ballistically along the chains, at constant speed, or diffusively.
      In our analysis of 2D SFG methods, we first describe a simpler situation where
      the visible probe pulse is effectively infinite in duration. This is the usual
      way time-resolved SFG measurements are made, and the SFG experiment then becomes
      a function of a single time delay, the pump-IR probe delay t(1). Unfortunately,
      in this case the SFG signals have a large contribution from the nonresonant (NR)
      background generated by the metal surface, which adds a great deal of noise to
      the data, and the time resolution is limited by the molecule's vibrational
      dephasing time constant T(2), which is often 1 ps or more. We have recently shown
      that the NR background can be suppressed using a time delay t(2) between IR and
      visible probe pulses. In this now 2D SFG method, one would expect that
      information about the molecular response to the pump pulses would be contained in
      slices along the t(1) axis, but by simulating the experiment we show that the
      t(1) and t(2) parameters interact. Changing t(2) to suppress the NR background
      causes t(1) slices to shift in time. We also show how to improve the time
      resolution of ultrafast SFG experiments while maintaining NR suppression using
      femtosecond visible pulses at appropriate t(2) delay values.

PMID- 19388672
TI  - Cytosolic targeting of macromolecules using a pH-dependent fusogenic peptide in
      combination with cationic liposomes.
AB  - pH-Sensitive peptides and polymers have been employed as additives to enhance the
      cytosolic delivery of drugs and genes by facilitating their endosomal escape.
      However, little attention has been paid to the intracellular fate of these
      peptides and polymers. In this study, we explored the possibility of utilizing
      GALA, a pH-sensitive fusogenic peptide, as a cytosol-targeting vehicle. In
      combination with cationic liposomes, Lipofectamine 2000 (LF2000), the feasibility
      of this approach for the cytosolic targeting of proteins and nanoparticles was
      exemplified through the delivery of avidin (68 kDa) and streptavidin-coated
      quantum dots (15-20 nm) in serum-containing medium. The use of cationic liposomes
      is critical to enhance the cell-surface adhesion of the GALA conjugates and
      eventual endosomal uptake. Circular dichroism studies suggest that the GALA can
      be liberated from cationic liposomes at a reducing pH to form a helical structure
      and this may eventually lead to disruption of the endosomal membrane to achieve
      an efficient leakage of the GALA conjugates into the cytosol.

PMID- 19388673
TI  - Site-specific, covalent labeling of recombinant antibody fragments via fusion to
      an engineered version of 6-O-alkylguanine DNA alkyltransferase.
AB  - Recombinant antibodies are promising tools for a wide range of bioanalytical and
      medical applications. However, the chemical modification of such molecules can be
      challenging, which limits their broader utilization. Here we describe a universal
      method for the site-specific labeling of antibody fragments and protein ligands
      by genetically fusing them to an engineered version of the human DNA-repair
      enzyme O(6)-alkyllguanine DNA alkyltransferase (AGT), known as SNAP-Tag (1-3) .
      Substrates containing O(6)-benzylguanine are covalently bound to the fusion
      proteins via a stable thioether bond in a rapid and highly specific self-labeling
      reaction. The coupling is site-directed, allowing the design and synthesis of
      antibody conjugates with predefined stoichiometry. We cloned a series of ligand
      SNAP-Tag fusion proteins and expressed them in HEK 293T cells. The
      antibody/ligand-fusions were characterized by labeling with different
      fluorophores, labeling with biotin, or by coupling them to fluorescent nanobeads,
      followed by analysis by flow cytometry and confocal microscopy. All ligands
      retained their original antigen-binding properties when fused to the SNAP-Tag.
      The combination of recombinant antibodies or protein ligands with the SNAP-Tag
      facilitates simple and efficient covalent modification with a broad range of
      substrates, thus providing a useful and advantageous alternative to existing
      coupling strategies.

PMID- 19388674
TI  - Glycosylated DOTA-alpha-melanocyte-stimulating hormone analogues for melanoma
      targeting: influence of the site of glycosylation on in vivo biodistribution.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH) is known to bind to the
      melanocortin receptor 1 (MC1R) which is overexpressed on melanotic and amelanotic
      melanoma cells. alpha-MSH analogues are potential candidates for specific
      targeting of melanoma metastases. Several linear and cyclic radiolabeled MSH
      peptides have been designed and tested in the past, showing both high affinity
      for the MC1R in vitro and good incorporation in tumor xenografts in vivo.
      However, considerable kidney reabsorption of the radiopeptides could not be
      avoided. With the aim to increase the tumor-to-kidney ratio, we synthesized six
      glycosylated derivatives of NAPamide, an alpha-MSH octapeptide analogue with high
      tumor selectivity and coupled them to the chelator DOTA (1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid). The peptides were evaluated in
      vitro for MC1R binding and bioactivity and, after labeling with (111)In, for in
      vitro cellular uptake and in vivo tissue distribution in mice carrying B16F1
      melanoma tumors. The glycopeptides showed excellent binding affinities in the low
      nanomolar to subnanomolar range using both murine and human melanoma cell lines.
      However, five glycopeptides displayed lower selectivity in vivo than the parent
      DOTA-NAPamide, because of either a lower tumor uptake or a higher kidney uptake.
      In particular C-terminal extension of the amide group by a galactosyl moiety
      increased the kidney retention dramatically. By contrast, an N-terminally
      positioned galactose residue in DOTA-Gal-NAPamide improved the tumor-to-kidney
      ratio (4-48 h AUC of 1.34) by a factor of about 1.2 as compared to the parent
      DOTA-NAPamide (4-48 h AUC of 1.11), thus serving as new lead compound for MC1R
      targeting molecules.

PMID- 19388675
TI  - Design and synthesis of small molecule glycerol 3-phosphate acyltransferase
      inhibitors.
AB  - The incidence of obesity and other diseases associated with an increased
      triacylglycerol mass is growing rapidly, particularly in the United States.
      Glycerol 3-phosphate acyltransferase (GPAT) catalyzes the rate-limiting step of
      glycerolipid biosynthesis, the acylation of glycerol 3-phosphate with saturated
      long-chain acyl-CoAs. In an effort to produce small molecule inhibitors of this
      enzyme, a series of benzoic and phosphonic acids was designed and synthesized. In
      vitro testing of this series has led to the identification of several compounds,
      in particular 2-(nonylsulfonamido)benzoic acid (15g), possessing moderate GPAT
      inhibitory activity in an intact mitochondrial assay.

PMID- 19388676
TI  - Novel, broad-spectrum anticonvulsants containing a sulfamide group: advancement
      of N-((benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into human clinical
      studies.
AB  - In seeking broad-spectrum anticonvulsants to treat epilepsy and other
      neurological disorders, we synthesized and tested a group of sulfamide
      derivatives (4a-k, 5), which led to the clinical development of 4a (JNJ
      26990990). This compound exhibited excellent anticonvulsant activity in rodents
      against audiogenic, electrically induced, and chemically induced seizures, with
      very weak inhibition of human carbonic anhydrase-II (IC(50) = 110 microM). The
      pharmacological profile for 4a supports its potential in the treatment of
      multiple forms of epilepsy, including pharmacoresistant variants.
      Mechanistically, 4a inhibited voltage-gated Na(+) channels and N-type Ca(2+)
      channels but was not effective as a K(+) channel opener. The pharmacokinetics and
      metabolic properties of 4a are discussed.

PMID- 19388677
TI  - Discovery process and pharmacological characterization of 2-(S)-(4-fluoro-2
      methylphenyl)piperazine-1-carboxylic acid [1-(R)-(3,5-bis
      trifluoromethylphenyl)ethyl]methylamide (vestipitant) as a potent, selective, and
      orally active NK1 receptor antagonist.
AB  - In an effort to discover novel druglike NK(1) receptor antagonists a new series
      of suitably substituted C-phenylpiperazine derivatives was identified by an
      appropriate chemical exploration of related N-phenylpiperazine analogues, with
      the specific aim to maximize their in vitro affinity and optimize in parallel
      their pharmacokinetic profile. Among the compounds synthesized, 2-(S)-(4-fluoro-2
      methylphenyl)piperazine-1-carboxylic acid [1-(R)-(3,5-bis
      trifluoromethylphenyl)ethyl]methylamide (vestipitant) was identified as one of
      the most in vitro potent and selective NK(1) receptor antagonists ever
      discovered, showing appropriate pharmacokinetic properties and in vivo activity.
      On the basis of its preclinical profile, this compound was selected as a drug
      candidate.

PMID- 19388678
TI  - Cross-linked chitosan/chitin crystal nanocomposites with improved permeation
      selectivity and pH stability.
AB  - This study is aimed at developing and characterizing cross-linked
      bionanocomposites for membrane applications using chitosan as the matrix, chitin
      nanocrystals as the functional phase, and gluteraldehyde as the cross-linker. The
      nanocomposites' chemistry and morphology were examined by estimation of gel
      content, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD),
      and atomic force microscopy (AFM), whereby the occurrence of cross-linking and
      nanoscale dispersion of chitin in the matrix was confirmed. Besides, cross
      linking and chitin whiskers content were both found to impact the water uptake
      mechanism. Cross-linking provided dimensional stability in acidic medium and
      significantly decreased the equilibrium water uptake. Incorporation of chitin
      nanocrystals provided increased permeation selectivity to chitosan in neutral and
      acidic medium.

PMID- 19388679
TI  - Complexes between high charge density cationic polyelectrolytes and anionic
      single- and double-tail surfactants.
AB  - Polyelectrolyte/surfactant complexes formed between well-defined linear flexible
      polyelectrolytes, namely, quaternized poly[3,5
      bis(dimethylaminomethylene)hydroxystyrene] (Q-N-PHOS), bearing two cationic sites
      on each repeating unit, and two different anionic surfactants, namely, sodium
      dodecyl sulfate (SDS) with one hydrocarbon tail and sodium bis(2-ethylhexyl)
      sulfosuccinate (AOT) with two hydrocarbon chains, are studied by means of
      fluorescence spectroscopy, electrophoretic, dynamic and static light scattering,
      and atomic force microscopy. Depending on the surfactant state in initial
      solutions (i.e., below or above nominal critical micelle concentration, cmc) and
      final (-/+) charge ratio, self-assembly in nanoparticles of variable size,
      stability, and effective charge is possible. Spherical, rather polydispserse
      complexes are formed in all cases. Critical aggregation concentrations (cac)
      depend on the surfactant type, while hydrophobicity of the main polyelectrolyte
      chain plays a role in colloidal stability of the complex nanoparticles.

PMID- 19388680
TI  - Low power visible-to-UV upconversion.
AB  - Low power visible-to-UV photon upconversion is demonstrated for the first time,
      achieved from two simple organic chromophores dissolved in benzene. Selective 442
      nm excitation of the triplet sensitizer 2,3-butanedione (biacetyl) in the
      presence of the laser dye 2,5-diphenyloxazole (PPO) results in the observation of
      singlet fluorescence from the latter in the UV centered at 360 nm, anti-Stokes
      shifted by a record 0.64 eV with respect to the excitation. All of the
      experimental data are consistent with the upconverted singlet PPO fluorescence
      being produced as a result of biacetyl-sensitized triplet-triplet annihilation
      (TTA) of triplet excited PPO chromophores. Nanosecond laser flash photolysis
      performed under pseudo-first-order conditions revealed the bimolecular rate
      constant of triplet-triplet energy transfer between the biacetyl sensitizer and
      PPO acceptor, k(q) = 9.0 x 10(8) M(-1)s(-1). The TTA process was confirmed by the
      quadratic dependence of the upconverted integrated PPO emission intensity
      measured with respect to incident 442 nm light power density. The maximum quantum
      yield of the upconverted emission (0.0058 +/- 0.0002) was determined relative to
      1,8-diphenyl-1,3,5,7-octatetraene, both measured with 0.389 W/cm(2) incident
      power density. The PPO triplet-triplet annihilation rate constant (k(TT)) was
      determined from transient absorption decays monitored at the peak of its
      characteristic triplet-to-triplet excited-state absorption (500 nm) as a function
      of incident pulsed laser fluence; this process attains the diffusion limit in
      benzene at room temperature, k(TT) = 1.1 +/- 0.1 x 10(10) M(-1) s(-1).

PMID- 19388682
TI  - Coupling of Raman radial breathing modes in double-wall carbon nanotubes and
      bundles of nanotubes.
AB  - Measurements of the radial breathing modes from Raman Spectroscopy have been most
      useful in characterizing the diameters of single-wall carbon nanotubes (SWNT),
      where there is a simple monotonic relationship between frequency and diameter.
      Similar correlations have also been used to predict sizes for double and multiple
      wall nanotubes and for bundles of SWNT. However this can lead to significant
      errors because the relationship between frequencies and diameter is much more
      complicated for DWNT. This is because of couplings between the vibrations of
      various walls. To provide guidance in such assignments we used the GraFF
      atomistic force field to predict the in-phase and counter-phase radial breathing
      modes (RBMs) of double wall carbon nanotubes (DWNTs) over a broad range of inner
      and outer diameters and chiralities. We then developed an analytical model to
      describe the RBMs of dispersed DWNTs. This enables the inner and outer shell
      diameters to be extracted from pairs of RBM peaks. We find that nanotubes bundles
      show significant dependent peak broadening and shifting compared to dispersed
      nanotubes. For bundles of SWNT and DWNT, the relationships are much more
      complicated.

PMID- 19388683
TI  - Single subcutaneous administration of RGDK-lipopeptide:rhPDGF-B gene complex
      heals wounds in streptozotocin-induced diabetic rats.
AB  - Development of effective therapeutics for chronic wounds remains a formidable
      clinical challenge. Deficiency of growth factors is of paramount importance among
      the multitude of factors contributing to the pathogenesis of diabetic wounds.
      Clinical interest has been witnessed in the past for exogenous applications of
      platelet derived growth factor B (PDGF-B) in chronic nonhealing wounds. However,
      accomplishing even modest favorable clinical effects in such topical applications
      requires large and repeated doses of PDGF-B proteins. Chronic wounds are being
      increasingly circumvented by gene therapy approach and to this end, cationic
      liposomes are emerging as promising nonviral carriers for delivering various
      growth factors encoding therapeutic genes to wound beds. However, as in case of
      topical application of growth factors, all the prior studies on the use of
      cationic liposomes in nonviral gene therapy of wounds involved repeated
      injections of cationic liposome:cDNA complexes over several weeks for ensuring
      complete wound healing. Herein, we show that a single subcutaneous administration
      of an electrostatic complex of rhPDGF-B plasmid, integrin receptor selective RGDK
      lipopeptide 1 and cholesterol (as auxiliary lipid) is capable of healing wounds
      in streptozotocin-induced diabetic Sprague-Dawley rats (as model of chronic
      wounds). Western blot analysis revealed significant expression of rhPDGF-B in
      mouse fibroblast cells transfected with RGDK-lipopeptide 1:rhPDGF-B lipoplex. The
      transfection efficiencies of the RGDK-lipopeptide 1 in mouse and human fibroblast
      cells preincubated with various monoclonal anti-integrin receptor antibodies
      support the notion that the cellular uptake of the RGDK-lipopeptide 1:DNA
      complexes in fibroblast cells is likely to be selectively mediated by alpha5beta1
      integrin receptors. Findings in the histopathological stainings using both
      hematoxylin and eosin (H & E) as well as Masson's Trichrome staining revealed a
      significantly higher degree of epithelization, keratization, fibrocollagenation
      and blood vessel formation in rats treated with RGDK-lipopeptide 1:rhPDGF
      compared to those in rats treated with vehicle alone.

PMID- 19388684
TI  - Methyl t-butyl ether and methyl trimethylsilyl ether ions dissociate near their
      ionization thresholds: a TPES, TPEPICO, RRKM, and G3 investigation.
AB  - The threshold photoelectron spectra and threshold photoelectron photoion
      coincidence (TPEPICO) mass spectra of methyl t-butyl ether, (CH(3))(3)COCH(3)
      (MTBE), and methyl trimethylsilyl ether, (CH(3))(3)SiOCH(3) (MTMSE), have been
      measured using synchrotron radiation. The effect of silicon substitution on the
      unimolecular dissociation processes and the threshold photoelectron spectrum has
      been investigated. Both molecular ions dissociate at low internal energies. For
      ionized MTBE, the parent ion is no longer observed at an internal energy of only
      0.2 eV. For this reason, it was not possible to fit the TPEPICO data to extract
      reliable thermochemical information. G3 level calculations place the molecular
      ion 5 kJ mol(-1) above the lowest-energy dissociation products,
      (CH(3))(2)COCH(3)(+) + (*)CH(3), suggesting the participation of an isomer,
      potentially the distonic ion (*)CH(2)(CH(3))(2)CO(+)(H)CH(3), in the
      dissociation. However, the calculations are not considered accurate enough to
      reliably determine the role this isomer plays, if any. RRKM modeling of the
      threshold region of the TPEPICO breakdown curves for ionized MTMSE leads to an
      E(0) for methyl loss of 63 +/- 2 kJ mol(-1), in good agreement with the G3 value
      of 66 kJ mol(-1). The resulting Delta(f)H(0) for (CH(3))(2)SiOCH(3)(+) of 384 +/-
      10 kJ mol(-1) (Delta(f)H(298) = 361 +/- 10 kJ mol(-1)) is 28 kJ mol(-1) lower
      than the G3 value of 412 kJ mol(-1) due to the G3 Delta(f)H(0) for neutral MTMSE
      being 16 kJ mol(-1) higher than the previously reported value and the fact that
      the experimental IE(a) is 6 kJ mol(-1) lower than the G3 estimate. Appearance
      energy values for higher-energy fragmentation channels up to 36 (for MTBE) and 32
      eV (for MTMSE) are reported and compared to literature values. An investigation
      of fragment ion peak broadening at high internal energy indicated that the two
      doubly charged molecular ions are not stable on the microsecond time scale. Each
      was found to dissociate into two singly charged ions along one or more neutral
      species.

PMID- 19388685
TI  - Anti-AIDS agents. 78. Design, synthesis, metabolic stability assessment, and
      antiviral evaluation of novel betulinic acid derivatives as potent anti-human
      immunodeficiency virus (HIV) agents.
AB  - In a continuing study of potent anti-HIV agents, seventeen 28,30-disubstituted
      betulinic acid (BA, 1) derivatives and seven novel 3,28-disubstituted BA
      analogues were designed, synthesized, and evaluated for in vitro antiviral
      activity. Among them, compound 21 showed an improved solubility and equal anti
      HIV potency (EC(50) = 0.09 microM) when compared to HIV entry inhibitors 3b
      (IC9564, (3R,4S)-N'-[N-[3beta-hydroxy-lup-20(29)-en-28-oyl]-8-aminooctanoyl]-4
      amino-3-hydroxy-6-methylheptanoic acid) and 4 (A43-D, [[N-[3beta-O-(3',3'
      dimethylsuccinyl)-lup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane). Using a
      cyclic secondary amine to form the C-28 amide bond increased the metabolic
      stability of the derivatives significantly in pooled human liver microsomes. The
      most potent compounds 47 and 48 displayed potent anti-HIV activity with EC(50)
      values of 0.007 and 0.006 microM, respectively. These results are slightly better
      than that of bevirimat (2, 3',3'-dimethylsuccinylbetulinic acid), which is
      currently in phase IIb clinical trials. Compounds 47 and 48 should serve as
      attractive promising leads to develop next generation, metabolically stable, 3,28
      disubstituted bifunctional HIV-1 inhibitors as clinical trials candidates.

PMID- 19388688
TI  - Molecular dynamics simulations of electrosprayed water nanodroplets: internal
      potential gradients, location of excess charge centers, and "hopping" protons.
AB  - Water nanodroplets charged with excess protons play a central role during
      electrospray ionization (ESI). In the current study molecular dynamics (MD)
      simulations were used for gaining insights into the nanodroplet behavior based on
      classical mechanics. The SPC/E water model was modified to permit the inclusion
      of protons as highly mobile point charges at minimum computational cost. A
      spherical trapping potential was assigned to every SPC/E oxygen, thereby allowing
      the formation of protonated water molecules. Within a tightly packed nanodroplet
      the individual potential wells merge to form a three-dimensional energy landscape
      that facilitates rapid proton hopping between water molecules. This approach
      requires short-range modifications to the standard Coulomb potential for modeling
      electrostatic proton-water interactions. Simulations on nanodroplets consisting
      of 1248 water molecules and 10 protons (radius, ca. 21 A) result in a proton
      diffusion coefficient that is in agreement with the value measured in bulk
      solution. Radial proton distributions extracted from 1 ns MD runs exhibit a large
      peak around 14 A, in addition to substantial population density closer to the
      droplet center. Similar radial distributions were found for nanodroplets charged
      with Na+ ions. This behavior is dramatically different from that expected on the
      basis of continuum electrostatic theory, which predicts that excess charge should
      be confined to a thin layer on the droplet surface. One important contributor to
      this effect seems to be the ordering of water molecules at the liquid/vacuum
      interface. This ordering results in an electrical double layer, generating a
      potential gradient that tends to pull positive charge carriers (such as protons,
      but also others such as Na+ ions) toward the droplet interior. This deviation
      from the widely assumed surface charge paradigm could have implications for the
      mechanism by which protonated analyte ions are formed during ESI.

PMID- 19388687
TI  - Products of oxidative stress inhibit aldehyde oxidation and reduction pathways in
      dopamine catabolism yielding elevated levels of a reactive intermediate.
AB  - Dopamine (DA) has been implicated as an endogenous neurotoxin to explain the
      selective neurodegeneration as observed for Parkinson's disease (PD). In
      addition, oxidative stress and lipid peroxidation are hypothesized culprits in PD
      pathogenesis. DA undergoes catabolism by monoamine oxidase (MAO) to 3,4
      dihydroxyphenylacetaldehyde (DOPAL), which is further oxidized to 3,4
      dihydroxyphenylacetic acid (DOPAC) via aldehyde dehydrogenase (ALDH). As a minor
      and compensatory metabolic pathway, DOPAL can be reduced to 3,4
      dihydroxyphenylethanol (DOPET) via cytosolic aldehyde or aldose reductase (AR).
      Previous studies have found DOPAL to be significantly more toxic to DA cells than
      DA and that the major lipid peroxidation products, that is, 4-hydroxynonenal
      (4HNE) and malondialdehyde (MDA), potently inhibit DOPAL oxidation via ALDH. The
      hypothesis of this work is that lipid peroxidation products inhibit DOPAL
      oxidation, yielding aberrant levels of the toxic aldehyde intermediate. To test
      this hypothesis, nerve growth factor-differentiated PC6-3 cells were used as a
      model for DA neurons. Cell viability in the presence of 4HNE and MDA (2-100
      microM) was measured by MTT assay, and it was found that only 100 microM 4HNE
      exhibited significant cytotoxicity. Treatment of cells with varying
      concentrations of 4HNE and MDA resulted in reduced DOPAC production and
      significant elevation of DOPAL levels, suggesting inhibition of ALDH. In cells
      treated with 4HNE that exhibited elevated DOPAL, there was a significant increase
      in DOPET. However, elevated DOPET was not observed for the cells treated with
      MDA, suggesting MDA to be an inhibitor of AR. Using isolated cytosolic AR, it was
      found that MDA but not 4HNE inhibited reductase activity toward DOPAL,
      surprisingly. These data demonstrate that the oxidative stress products 4HNE and
      MDA inhibit the aldehyde biotransformation step of DA catabolism yielding
      elevated levels of the endogenous neurotoxin DOPAL, which may link oxidative
      stress to selective neurodegeneration as seen in PD.

PMID- 19388689
TI  - Interaction of hydrated protons with trioctylphosphine oxide: NMR and theoretical
      study.
AB  - Interaction of trioctylphosphine oxide (TOPO) with fully ionized hydrated protons
      (HP) was studied in acetonitrile-d(3) and nitrobenzene-d(5) using (1)H, (13)C,
      and (31)P NMR, PFG NMR, and magnetic relaxation, and the experimental results
      were confronted with high-precision ab initio DFT calculations. Relative chemical
      shifts of NMR signals of TOPO (0.02 mol/L) under the presence of HP in the molar
      ratio beta = 0-2.0 mol/mol show binding between TOPO and HP. Self-diffusion
      measurements using (1)H PFG NMR demonstrate that larger complexes with higher
      content of TOPO are generally formed at beta < 0.75. Analyzing the dependence of
      (31)P NMR chemical shifts on beta by the use of program LETAGROP, we obtained
      very good fitting for the assumed coexistence of three complexes (TOPO)(i).HP
      (named C(i)), where i = 1, 2, 3. The logarithms of the respective stabilization
      constants log K(i) were found to be 3.63, 4.67, and 7.23 in acetonitrile and
      3.91, 6.04, and 7.92 in nitrobenzene. The (31)P NMR chemical shifts Deltadelta(i)
      corresponding to these complexes are 39.35, 29.51, and 19.72 ppm in acetonitrile
      and 38.37, 28.47, and 18.63 ppm in nitrobenzene. These values and the calculated
      values of alpha(i) =[C(i)]/[TOPO](0) were utilized in the analysis of the system
      dynamics. This was done by measuring the transverse (31)P NMR relaxation by the
      CPMG sequence with varying delays t(p) between the pi pulses in the mixtures with
      beta = 0.5, 1.25, and 1.5. Calculating the probabilities of imaginable exchange
      processes shows that only three of them can have significant influence on
      relaxation rate R(2), namely C(1) <--> TOPO, C(2) <--> C(1), and C(3) <--> C(2).
      Using the slopes of the R(2)-t(p)(-1) dependences in the above three mixtures,
      the following correlation times were obtained: tau(10) = 2.5 x 10(-6), tau(21) =
      7.4 x 10(-5), tau(32) = 11.3 x 10(-5) s. The DFT calculations support the
      hypothesis that complexes C(1) to C(3) are the main species in the mixtures of
      TOPO with HP, with the only exception that additional water molecules are bound
      to the complexes in the case of C(1) and C(2). Schematically, the compositions of
      the three stable complexes is [3TOPO.H(3)O](+), [2TOPO.H(3)O.H(2)O](+), and
      [TOPO.H(3)O.2H(2)O](+). The relative (31)P NMR shifts calculated for the
      optimized structures of C(1), C(2), and C(3) are in very good agreement with the
      experimentally observed values.

PMID- 19388690
TI  - Intrinsic potential of cell membranes: opposite effects of lipid transmembrane
      asymmetry and asymmetric salt ion distribution.
AB  - Using atomic-scale molecular dynamics simulations, we consider the intrinsic cell
      membrane potential that is found to originate from a subtle interplay between
      lipid transmembrane asymmetry and the asymmetric distribution of monovalent salt
      ions on the two sides of the cell membrane. It turns out that both the asymmetric
      distribution of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipids
      across a membrane and the asymmetric distribution of NaCl and KCl induce nonzero
      drops in the transmembrane potential. However, these potential drops are opposite
      in sign. As the PC leaflet faces a NaCl saline solution and the PE leaflet is
      exposed to KCl, the outcome is that the effects of asymmetric lipid and salt ion
      distributions essentially cancel one another almost completely. Overall, our
      study highlights the complex nature of the intrinsic potential of cell membranes
      under physiological conditions.

PMID- 19388691
TI  - One- and two-photon stimulated emission depletion of a sulfonyl-containing
      fluorene derivative.
AB  - One- and two-photon stimulated emission transitions were investigated by the
      fluorescence quenching of a sulfonyl-containing fluorene compound, 2,7-bis(4
      (phenylsulfonyl)styryl)-9,9-didecyl-9H-fluorene (1), in solution at room
      temperature using a picosecond pump-probe technique. The nature of stimulated
      transitions under various fluorescence excitation and quenching conditions was
      analyzed theoretically, and good agreement with experimental data was
      demonstrated. Two-photon stimulated transitions S1-->S0 were shown for 1 at
      lambdaq=1064 nm, representing the first report of two-photon stimulated emission
      depletion (STED) in a molecular system. The two-photon stimulated emission cross
      section, delta2PE(lambdaq), of fluorene 1 was estimated to be approximately 240
      280 GM, suggesting that this compound may be a good candidate for use in two
      photon STED microscopy.

PMID- 19388692
TI  - Self-association of naphthalene at the air-ice interface.
AB  - We present a molecular dynamics study of the interactions between two molecules
      of naphthalene present at air-water versus air-ice interfaces. In agreement with
      the inference from our previous experimental work [Kahan, T. F.; Donaldson, D. J.
      J. Phys. Chem. A 2007, 111, 1277], the results suggest that self-association of
      the molecules is more likely to take place on the ice surface than on the water
      surface. A shorter average distance between the two naphthalene molecules, in
      conjunction with a stronger interaction energy and free energy of association,
      point to a stronger tendency to self-associate on ice than on water. The distinct
      behavior at the two interfaces appears be due to more favorable interactions
      between naphthalene molecules on liquid water surfaces than on ice surfaces.

PMID- 19388693
TI  - Conformational cooling dynamics in matrix-isolated 1,3-butanediol.
AB  - The complete conformational space of monomeric 1,3-butanediol has been
      characterized theoretically, and 73 unique stable conformers were found at the
      MP2/6-311++G(d,p) level. These were classified into nine families whose members
      share the same heavy atom backbone configurations and differ in the hydrogen atom
      orientations. The first and third most populated backbone families are governed
      by the formation of an intramolecular hydrogen bond; however, the second
      precludes this type of interaction and was frequently overlooked in previous
      studies. Its stability is determined by the relatively high entropy of its main
      conformers. The hydrogen bonding of four of the most important conformers was
      characterized by means of atoms in molecules (AIM, also known as QTAIM) and
      natural bond orbital (NBO) analyses. Using appropriate isodesmic reactions,
      hydrogen bonding energy stabilizations of 12-14 kJ mol(-1) have been found.
      Experimentally, monomeric molecules of 1,3-butanediol were isolated in low
      temperature inert matrixes, and their infrared spectra were analyzed from the
      viewpoint of the conformational distribution. All the relevant transition states
      for the conformational interconversion reaction paths were characterized at the
      same level of theory to interpret the conformational cooling dynamics observed in
      the low-temperature matrixes. The energy barriers for rotation of the OH groups
      were calculated to be very low (<3 kJ mol(-1)). These barriers were overcome in
      the experiments at 10 K (Ar matrix), in the process of matrix deposition, and
      population within each family was reduced to the most stable conformers. Further
      increase in the substrate temperature (up to 40 K, Xe matrix) resulted in
      conformational cooling where the medium-height barriers (approximately 13 kJ mol(
      1)) could be surmounted and all conformational population converted to the ground
      conformational state. Remarkably, this state turned to consist of two forms of
      the most stable hydrogen bonded family, which were predicted by calculations to
      be accidentally degenerated and were found in the annealed matrix in equal
      amounts. All of these experimentally observed conformational cooling processes
      were analyzed and supported by full agreement with the theoretical calculations.

PMID- 19388694
TI  - Enantiomer-selective and helix-sense-selective living block copolymerization of
      isocyanide enantiomers initiated by single-handed helical poly(phenyl
      isocyanide)s.
AB  - Rigid-rodlike right (P)- and left (M)-handed helical polyisocyanides (P-poly-L-1
      and M-poly-L-1) prepared by the living polymerization of an enantiomerically pure
      phenyl isocyanide bearing an L-alanine pendant with a long n-decyl chain (L-1)
      with the mu-ethynediyl Pt-Pd catalyst were found to block copolymerize L-1 and D
      1 in a highly enantiomer-selective manner while maintaining narrow molecular
      weight distributions. The M-poly-L-1 preferentially copolymerized L-1 over the
      antipode D-1 by a factor of 6.4-7.7, whereas the D-1 was preferentially
      copolymerized with P-poly-L-1 composed of the same L-1 units, but possessing the
      opposite helicity by a factor of 4.0. Circular dichroism and high-resolution
      atomic force microscopy revealed that the enantiomer-selective block
      copolymerizations proceed in an extremely high helix-sense-selective fashion, and
      the preformed helical handedness determines the overall helical sense of the
      polyisocyanides irrespective of the configuration of the monomer units of the
      initiators during the block copolymerizations. The block copolymers are rigid-rod
      helical polymers with a narrow molecular weight distribution and exhibit a
      lyotropic smectic liquid crystalline phase.

PMID- 19388695
TI  - "Signal-on" detection of DNA hole transfer at the single molecule level.
AB  - The DNA base stack provides unique features for the efficient long-range charge
      transfer. For the purpose of investigating the hole transfer process of
      individual DNA and the optical readout of DNA information at the single molecule
      level, we performed single-molecule detection of DNA hole transfer (DNA HT) using
      single-molecule fluorescence spectroscopy. We have established the single
      molecule detection of DNA HT at the single molecule level based on the
      fluorescence generation by combining the oxidative reaction of the quencher
      molecule through DNA HT and the cancellation of FRET. This "signal-on" detection
      system makes it possible to detect DNA HT in individual DNA and the base-pair
      mismatch in the target DNA with high sensitivity and accuracy.

PMID- 19388696
TI  - Fluorescent J-aggregates of core-substituted perylene bisimides: studies on
      structure-property relationship, nucleation-elongation mechanism, and sergeants
      and-soldiers principle.
AB  - A series of highly soluble and fluorescent, at core tetraaryloxy-substituted and
      in imide positions hydrogen atom containing perylene bisimide (PBI) dyes 1a-e
      with varying peripheral side chains have been synthesized and thoroughly
      characterized. The self-assembly of these PBIs has been studied in detail by
      UV/vis, linear dichroism (LD) and circular dichroism (CD) spectroscopy, and
      scanning probe microscopy (AFM, STM). These studies revealed that the present
      PBIs self-assemble into extended double string cables, which consist of two
      hydrogen-bonded supramolecular polymeric chains of densely packed and strongly
      excitonically coupled PBI chromophores, providing highly fluorescent J
      aggregates. The aggregation strength ("melting" temperature) and the fluorescence
      properties of these J-aggregates are dependent on the number and chain length of
      the peripheral alkoxy substituents, thus revealing a structure-property
      relationship. In contrast to previously reported assemblies of PBIs, for which
      the aggregation process is described by the isodesmic (or equal K) model, a
      cooperative nucleation-elongation mechanism applies for the aggregation of the
      present assemblies as revealed by concentration-dependent UV/vis absorption
      studies with the chiral PBI 1e, providing equilibrium constants for dimerization
      (= nucleation) of K(2) = 13 +/- 11 L mol(-1) and for elongation of K = 2.3 +/-
      0.1 x 10(6) L mol(-1) in methylcyclohexane (MCH). LD spectroscopic measurements
      have been performed to analyze the orientation of the monomers within the
      aggregates. The nonlinearity of chiral amplification in PBI aggregates directed
      by sergeants-and-soldiers principle has been elucidated by coaggregation
      experiments of different PBI dyes using CD spectroscopy. The dimensions as well
      as the molecular arrangement of the monomeric units in assemblies have been
      explored by atomic force microscopy (AFM) and scanning tunneling microscopy
      (STM).

PMID- 19388697
TI  - Dioxygen and water activation processes on multi-Ru-substituted polyoxometalates:
      comparison with the "blue-dimer" water oxidation catalyst.
AB  - Dioxygen and water activation on multi-Ru-substituted polyoxometalates were
      studied using the B3LYP density functional method. It was shown that the reaction
      of the Ru(2)-substituted gamma-Keggin polyoxotungstate {gamma-[(H(2)O)Ru(III)-(mu
      OH)(2)-Ru(III)(H(2)O)][SiW(10)O(36)]}(4-), I(H(2)O), with O(2) is a 4-electron
      highly exothermic [DeltaE(gas) = 62.5 (DeltaE(gas) + DeltaG(solv(water)) = 24.6)
      kcal/mol] process and leads to formation of (H(2)O){gamma-[(O)Ru-(mu-OH)(2)
      Ru(O)](H(2)O)[SiW(10)O(36)]}(4-), IV(H(2)O). Both the stepwise (or dissociative)
      and the concerted (or associative) pathways of this reaction occurring with and
      without water dissociation, respectively, were examined, and the latter has been
      found to be kinetically more favorable. It was shown that the first 1e-oxidation
      is achieved by the H(2)O-to-O(2) substitution, which might occur with a maximum
      of 23.1 (10.5) kcal/mol barrier and leads to the formation of {gamma-[(OO)Ru-(mu
      OH)(2)-Ru(H(2)O)](H(2)O)[SiW(10)O(36)]}(4-), II(H(2)O). The second 1e-oxidation
      is initiated by the proton transfer from the coordinated water molecule to the
      superoxide (OO(-)) ligand in II(H(2)O) and is completed upon formation of
      hydroperoxo-hydroxo intermediate {gamma-[(OOH)Ru-(mu-OH)(2)
      Ru(OH)](H(2)O)[SiW(10)O(36)]}(4-), III-1(H(2)O). The final 2e-oxidation occurs
      upon the proton transfer from the terminal OH-ligand to the Ru-coordinated OOH
      fragment and is completed at the formation of (H(2)O)...{gamma-[(O)Ru-(mu-OH)(2)
      Ru(O)](H(2)O)[SiW(10)O(36)]}(4-), IV(H(2)O), with two Ru=O bonds. Each step in
      the associative pathway is exothermic and occurs with small energy barriers.
      During the process, the oxidation state of Ru centers increases from +3 to +4.
      The resulting IV(H(2)O) with a {Ru(O)-(mu-OH)(2)-Ru(O)} core should be formulated
      to have the Ru(IV)=O(*) units, rather than the Ru(V)=O groups. The reverse
      reaction, water oxidation by IV(H(2)O), is found to be highly endothermic and
      cannot occur; this finding is different from that reported for the "blue-dimer"
      intermediate, {(bpy)(2)[(O(*))Ru-(mu-O)-Ru(O(*))](bpy)(2)}(4+), which readily
      oxidized an incoming water molecule to produce O(2). The main reason for this
      difference in reactivity of IV(H(2)O) (i.e., Ru(2)-POM) and the "blue-dimer"
      intermediates toward the water molecule is found to be a high stability of
      IV(H(2)O) as compared to the analogous "blue-dimer" intermediate relative to O(2)
      formation. This, in turn, derives from the electron-rich nature of
      [SiW(10)O(36)](4-) as compared to bpy ligands.

PMID- 19388698
TI  - Histidine-containing radicals in the gas phase.
AB  - Radicals containing the histidine residue have been generated in the gas phase by
      femtosecond electron transfer to protonated histidine-N-methylamide (1H+), Nalpha
      acetylhistidine-N-methylamide (2H+), Nalpha-glycylhistidine (3H+), and Nalpha
      histidylglycine (4H+). Radicals generated by collisional electron transfer from
      dimethyldisulfide to ions 1H+ and 2H+ at 7 keV collision energies were found to
      dissociate completely on the microsecond time scale, as probed by reionization to
      cations. The main dissociations produced fragments from the imidazole side chain
      and the cleavage of the C(alpha)CO bond, whereas products of NCalpha bond
      cleavage were not observed. Electron transfer from gaseous potassium atoms to
      ions 3H+ and 4H+ at 2.97 keV collision energies not only caused backbone NCalpha
      bond dissociations but also furnished fractions of stable radicals that were
      detected after conversion to anions. Ion structures, ion-electron recombination
      energies, radical structures, electron affinities, and dissociation and
      transition-state energies were obtained by combined density functional theory and
      Moller-Plesset perturbational calculations (B3-PMP2) and basis sets ranging from
      6-311+G(2d,p) to aug-cc-pVTZ. The Rice-Ramsperger-Kassel-Marcus theory was used
      to calculate rate constants on the B3-PMP2 potential energy surfaces to aid
      interpretation of the mass spectrometric data. The stability of Nalpha
      histidylglycine-derived radicals is attributed to an exothermic isomerization in
      the imidazole ring, which is internally catalyzed by reversible proton transfer
      from the carboxyl group. The isomerization depends on the steric accessibility of
      the histidine side chain and the carboxyl group and involves a novel cation
      radical-COO salt-bridge intermediate.

PMID- 19388700
TI  - Periodic trends and index of boron LEwis acidity.
AB  - Lewis acidity is customarily gauged by comparing the relative magnitude of
      coordinate covalent bonding energies, where the Lewis acid moiety is varied and
      the Lewis base is kept constant. However, the prediction of Lewis acidity from
      first principles is sometimes contrary to that suggested by experimental bond
      energies. Specifically, the order of boron trihalide Lewis acidities predicted
      from substituent electronegativity arguments is opposite to that inferred by
      experiment. Contemporary explanations for the divergence between theory,
      computation, and experiment have led to further consternation. Due to the
      fundamental importance of understanding the origin of Lewis acidity, we report
      periodic trends for 21 boron Lewis acids, as well as their coordinate covalent
      bond strengths with NH(3), utilizing ab initio, density functional theory, and
      natural bond orbital analysis. Coordinate covalent bond dissociation energy has
      been determined to be an inadequate index of Lewis acid strength. Instead,
      acidity is measured in the manner originally intended by Lewis, which is defined
      by the valence of the acid of interest. Boron Lewis acidity is found to depend
      upon substituent electronegativity and atomic size, differently than for known
      Bronsted-Lowry periodic trends. Across the second period, stronger substituent
      electronegativity correlates (R(2) = 0.94) with increased Lewis acidity. However,
      across the third period, an equal contribution from substituent electronegativity
      and atomic radii is correlated (R(2) = 0.98) with Lewis acidity. The data suggest
      that Lewis acidity depends upon electronegativity solely down group 14, while
      equal contribution from both substituent electronegativity and atomic size are
      significant down groups 16 and 17. Originally deduced from Pauling's
      electronegativities, boron's substituents determine acidity by influencing the
      population of its valence by withdrawing electron density. However, size effects
      manifest differently than previously considered, where greater sigma bond (not pi
      bond) orbital overlap between boron and larger substituents increase the electron
      density available to boron's valence, thereby decreasing Lewis acidity. The
      computed electronegativity and size effects of substituents establish unique
      periodic trends that provide a novel explanation of boron Lewis acidity,
      consistent with first principle predictions. The findings resolve ambiguities
      between theory, computation, and experiment and provide a clearer understanding
      of Lewis acidity.

PMID- 19388699
TI  - Deletion of (54)FLRAPSWF(61) residues decreases the oligomeric size and enhances
      the chaperone function of alphaB-crystallin.
AB  - AlphaB-crystallin is a member of the small heat shock protein family and is known
      to have chaperone activity. Using a peptide scan approach, we previously
      determined that regions 42-57, 60-71, and 88-123 in alphaB-crystallin interact
      with alphaA-crystallin during heterooligomer formation. To further characterize
      the significance of the N-terminal domain of alphaB-crystallin, we prepared a
      deletion mutant that lacks residues (54)FLRAPSWF(61) (alphaBDelta54-61) and found
      that the absence of residues 54-61 in alphaB-crystallin significantly decreased
      the homooligomeric mass of alphaB-crystallin. The average oligomeric mass of wild
      type alphaB-crystallin and of alphaBDelta54-61, calculated using multiangle light
      scattering, was 624 and 382 kDa, respectively. The mutant subunits aggregate to
      form smaller, less-compact oligomers with a 4-fold increase in subunit exchange
      rate. Deletion of the 54-61 region resulted in a 50% decrease in intrinsic
      tryptophan fluorescence. The alphaBDelta54-61 mutant showed a 2-fold increase in
      1,1'-bi(4-anilino)naphthalene-5,5'-disulfonic acid (bis-ANS) binding as compared
      to the wild-type protein, suggesting increased hydrophobicity of the mutant
      protein. Accompanying the evidence of increased hydrophobicity in the deletion
      mutant was a 10-fold increase in antiaggregation activity. Homooligomers of
      6HalphaA (750 kDa) readily exchanged subunits with alphaBDelta54-61 homooligomers
      at 37 degrees C, forming heterooligomers with an intermediate mass of 625 kDa.
      Our data suggest that residues (54)FLRAPSWF(61) contribute to the higher order
      assembly of alphaB-crystallin oligomers. Residues (54)FLRAPSWF(61) in alphaB
      crystallin are not essential for target protein binding during chaperone action,
      but this region apparently has a role in the chaperone activity of native alphaB
      crystallin.

PMID- 19388701
TI  - Selective formation of spiro dihydrofurans and cyclopropanes through unexpected
      reaction of aldehydes with 1,3-dicarbonyl compounds.
AB  - An efficient methodology for the oxidative addition reaction of various aldehydes
      with 5,5-dimethylcyclohexane-1,3-dione and 1,3-indandione to selectively afford
      spiro dihydrofuran and cyclopropane derivatives, promoted by molecular iodine and
      dimethylaminopyridine under mechanical milling conditions, has been demonstrated.
      The products were obtained in good to excellent yields. A possible mechanism of
      this unusual reaction process is proposed.

PMID- 19388702
TI  - Role of the anion-binding site in catalysis and regulation of Mycobacterium
      tuberculosis D-3-phosphoglycerate dehydrogenase.
AB  - D-3-Phosphoglycerate dehydrogenase from Mycobacterium tuberculosis displays
      substantial substrate inhibition in the direction of NADH oxidation by its
      physiological substrate, hydroxypyruvic acid phosphate (HPAP). Previous
      investigations showed that plots of substrate concentration versus activity
      derived from steady state assays could be fit with the equation for complete
      uncompetitive inhibition and that the mechanism may be allosteric. This
      investigation uses a simulation of transient kinetic data to demonstrate that the
      mechanism is consistent with the interaction of substrate at a second site called
      the anion-binding site. While addition of substrate at the active site is
      ordered, with HPAP binding before NADH, NADH can compete with the substrate for
      binding to the allosteric site and thereby eliminate the substrate inhibition.
      Fluorescence resonance energy transfer analysis of mutants with specific
      tryptophan residues converted to phenylalanine residues demonstrates that the
      main interaction of NADH with the enzyme, in the absence of substrate, is at the
      allosteric anion-binding site. This is further confirmed by mutations of basic
      residues at the anion-binding site which also demonstrates that these residues
      are necessary for inhibition by l-serine when it binds to the regulatory domain.
      This may indicate that a ligand must be bound to the anion-binding site for l
      serine inhibition, providing a potential mechanism for low levels of activity in
      the presence of high levels of inhibitor.

PMID- 19388703
TI  - Electric field alignment of a block copolymer nanopattern: direct observation of
      the microscopic mechanism.
AB  - Using quasi-in-situ scanning force microscopy we study the details of nanopattern
      alignment in ABC terblock copolymer thin films in the presence of an in-plane
      electric field. Because of the surface interactions and electric field the
      lamellae are oriented both perpendicular to the plane of the film and parallel to
      the electric field. We identified two distinct defect types which govern the
      orientation mechanism. Ring-like (tori) and open-end defects dominate at the
      early stage of the orientation process, while mainly classic topological defects
      (disclinations and dislocations) are involved in long-range ordering at the late
      stages. Comparison of the time evolution of the defect density with the evolution
      of the orientational order parameter suggests that tori-defects are essential for
      the effective reorientation. Further, the quasi-in-situ SFM imaging allowed us to
      elucidate the influence of the electric field strength on the propagation
      velocity of the topological defects.

PMID- 19388704
TI  - Two-dimensional southwestern blotting and characterization of transcription
      factors on-blot.
AB  - Two-dimensional Southwestern blotting (2D-SW) described here combines several
      steps. Proteins are separated by two-dimensional gel electrophoresis and
      transferred to nitrocellulose (NC) or polyvinylidene fluoride (PVDF) membrane.
      The blotted proteins are then partially renatured and probed with a specific
      radiolabeled oligonucleotide for Southwestern blotting (SW) analysis. The
      detected proteins are then processed by on-blot digestion and identified by LC
      MS/MS analysis. A transcription factor, bound by a specific radiolabeled element,
      is thus characterized without aligning with protein spots on a gel. In this
      study, we systematically optimize conditions for 2D-SW and on-blot digestion. By
      quantifying the SW signal using a scintillation counter, the optimal conditions
      for SW were determined to be PVDF membrane, 0.5% PVP40 for membrane blocking,
      serial dilution of guanidine HCl for denaturing and renaturing proteins on the
      blot, and an SDS stripping buffer to remove radiation from the blot. By the
      quantification of the peptide yields using nano-ESI-MS analysis, the optimized
      conditions for on-blot digestions were found to be 0.5% Zwittergent 3-16 and 30%
      acetonitrile in trypsin digestion buffer. With the use of the optimized 2D-SW
      technique and on-blot digestion combined with HPLC-nano-ESI-MS/MS, a GFP-C/EBP
      model protein was successfully characterized from a bacterial extract, and native
      C/EBP beta was identified from 100 microg of HEK293 nuclear extract without any
      previous purification.

PMID- 19388705
TI  - Limazepines A-F, pyrrolo[1,4]benzodiazepine Antibiotics from an Indonesian
      Micrococcus sp.
AB  - In our screening of Indonesian microorganisms for novel bioactive natural
      products we have isolated seven new compounds, designated as limazepines A, B1
      and B2 (isolated as an isomeric mixture), C, D, E, and F, from the culture broth
      of Micrococcus sp. strain ICBB 8177. In addition, the known natural products
      prothracarcin and 7-O-succinylmacrolactin A, as well as two previously reported
      synthetic compounds, 2-amino-3-hydroxy-4-methoxybenzoic acid methyl ester and 4
      ethylpyrrole-2-carboxaldehyde, were obtained from the extract. Chemical
      structures were determined by spectroscopic methods and by comparison with the
      NMR data of structurally related compounds. The limazepines belong to the growing
      group of the pyrrolo[1,4]benzodiazepine antitumor antibiotics isolated from
      various soil bacteria. Limazepines B1/B2 mixture, C, and E were active against
      the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium
      Escherichia coli. Limazepine D was also active against S. aureus, but was not
      active against E. coli. Interestingly, only the limazepines B1/B2 mixture and D
      were active against Pseudomonas aeruginosa.

PMID- 19388707
TI  - Trinorsesquiterpenoids from the root extract of Pentalinon andrieuxii.
AB  - Two unusual trinorsesquiterpenoids, urechitols A (1) and B (2), were isolated
      from the root extract of Pentalinon andrieuxii, a plant used commonly in
      Yucatecan traditional medicine to treat leishmaniasis. The structures of 1 and 2
      were identified by interpretation of their spectroscopic data and chemical
      correlation reactions. The relative stereochemistry of 1 was confirmed through an
      X-ray crystallographic study.

PMID- 19388706
TI  - Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin,
      and curcumin.
AB  - Xanthine oxidoreductase (XOR) is a molybdenum-containing enzyme that under
      physiological conditions catalyzes the final two steps in purine catabolism,
      ultimately generating uric acid for excretion. Here we have investigated four
      naturally occurring compounds that have been reported to be inhibitors of XOR in
      order to examine the nature of their inhibition utilizing in vitro steady-state
      kinetic studies. We find that luteolin and quercetin are competitive inhibitors
      and that silibinin is a mixed-type inhibitor of the enzyme in vitro, and, unlike
      allopurinol, the inhibition is not time-dependent. These three natural products
      also decrease the production of superoxide by the enzyme. In contrast, and
      contrary to previous reports in the literature based on in vivo and other
      nonmechanistic studies, we find that curcumin did not inhibit the activity of
      purified XO nor its superoxide production in vitro.

PMID- 19388708
TI  - (S)-2-pentyl (R)-3-hydroxyhexanoate, a banana volatile and its olfactory
      recognition by the common fruit fly, Drosophila melanogaster.
AB  - The volatile organic compounds emitted from ripening bananas that elicit an
      antennal response from the common fruit fly, Drosophila melanogaster, were
      analyzed by a combination of gas chromatographic-electroantennographic detection,
      mass spectrometry, and (1)H NMR spectroscopy. These analyses revealed that the
      headspace of ripening bananas contains a number of EAD-active components
      including the new ester (S)-2-pentyl (R)-3-hydroxyhexanoate, the structural
      assignment of which was confirmed by chemical synthesis.

PMID- 19388709
TI  - Oleanane-type isomeric triterpenoids from Barringtonia racemosa.
AB  - Two new isomeric acylated oleanane-type triterpenoids along with three known
      compounds were isolated from the MeOH extract of the dried fruits of Barringtonia
      racemosa. On the basis of spectroscopic methods, with special emphasis on 1D and
      2D NMR techniques as well as chemical methods, the structures were characterized
      as racemosol A (1) [22alpha-acetoxy-3beta,15alpha,16alpha,21beta-tetrahydroxy-28
      (2-methylbutyryl)olean-12-ene] and isoracemosol A (2) [21beta-acetoxy
      3beta,15alpha,16alpha,28-tetrahydroxy-22alpha-(2-methylbutyryl)olean-12-ene]. The
      isolated compounds (1-5) were not active against HeLa and P388 D1 carcinoma cell
      lines.

PMID- 19388711
TI  - Regioselective bromination tactics in the de novo synthesis of chlorophyll b
      analogues.
AB  - The ability to introduce substituents at designated sites about the perimeter of
      the chlorin or 13(1)-oxophorbine macrocycle is essential for fundamental studies
      related to chlorophylls. A chlorin is a dihydroporphyrin, whereas a 13(1)
      oxophorbine is a chlorin containing an annulated oxopentano ring spanning
      positions 13 and 15. 13(1)-Oxophorbines bearing auxochromes at the 7-position of
      the macrocycle are valuable targets given their resemblance to chlorophyll a or
      b, which contains the 13(1)-oxophorbine skeleton and bears a 7-methyl or 7-formyl
      group, respectively. A rational route to 7-substituted 13(1)-oxophorbines was
      developed that relies on a new method for regioselective bromination. Under
      neutral conditions, a 13-acetyl-10-mesitylchlorin (FbC-M(10)A(13)) undergoes
      bromination (with 1 molar equiv of NBS in THF) both in ring B (7-position) and at
      the 15-position (42% versus 28% isolated yield), thereby thwarting installation
      of the isocyclic ring (ring E, spanning the 13-15 positions). Under acidic
      conditions (10% TFA in CH(2)Cl(2)), ring B is deactivated, and bromination occurs
      preferentially at the 15-position (87% yield). The capability for preferential 15
      bromination is essential to install the isocyclic ring, after which bromination
      can be directed to the 7-position of ring B (neutral conditions, 86% yield). The
      ability to suppress bromination in ring B (under acidic media) has been exploited
      in syntheses of sparsely substituted analogues of chlorophyll b. The analogues
      contain a 7-substituent (acetyl, formyl, or TIPS-ethynyl), a 10-mesityl group,
      and the 18,18-dimethyl group as the only substituents in the 13(1)-oxophorbine
      skeleton. The three analogues exhibit absorption spectral features that closely
      resemble those of free base analogues of chlorophyll b. Taken together, the
      facile access to chlorins and 13(1)-oxophorbines bearing substituents at distinct
      sites should enable fundamental spectroscopic studies and diverse applications.

PMID- 19388712
TI  - DFT study on bifunctional chiral Bronsted acid-catalyzed asymmetric
      hydrophosphonylation of imines.
AB  - Asymmetric hydrophosphonylation reaction of aldimines with dialkyl phosphites
      proceeds catalytically by means of a phosphoric acid diester, derived from (R)
      BINOL, as a chiral Bronsted acid to afford alpha-amino phosphonates with good to
      high enantioselectivities (up to 90% ee). The use of the aldimines derived from
      cinnamaldehyde derivatives and sterically demanding dialkyl phosphites was
      essential for achieving high enantioselectivity as well as high yield. To
      elucidate the reaction mechanism and the origin of the high enantioselectivity,
      DFT calculation (BHandHLYP/6-31G*) was carried out. The reaction proceeds via the
      nine-membered zwitterionic transition state (TS) with the chiral phosphoric acid,
      where aldimine and phosphite could be activated by the Bronsted acidic site and
      Lewis basic site, respectively. The si-facial attacking TS could be less favored
      by the steric repulsion of 3,3'-aryl groups on the chiral phosphoric acid with
      the bulky phosphite. When using the aldimine derived from benzaldehyde, the re
      facial attacking TS is destabilized to decrease the enantioselectivity in
      agreement with the experimental results.

PMID- 19388713
TI  - Electron-accepting conjugated materials based on 2-vinyl-4,5-dicyanoimidazoles
      for application in organic electronics.
AB  - We report the Heck coupling of 2-vinyl-4,5-dicyanoimidazole (vinazene) with
      selected di- and trihalo aromatics in an effort to prepare linear and branched
      electron-accepting conjugated materials for application in organic electronics.
      By selecting the suitable halo-aromatic moiety, it is possible to tune the HOMO
      LUMO energy levels, absorption, and emission properties for a specific
      application. In this regard, materials with strong photoluminescence from blue -
      > green --> red are reported that may have potential application in organic light
      emitting diodes (OLEDs). Furthermore, derivatives with strong absorption in the
      visible spectrum, coupled with favorable HOMO-LUMO levels, have been used to
      prepare promising organic photovoltaic devices (OPVs) when combined with
      commercially available semiconducting donor polymers.

PMID- 19388714
TI  - Photophysical study of blue, green, and orange-red light-emitting carbazoles (1).
AB  - Simple synthetic procedures have been developed to prepare suitably substituted
      stable carbazoles B1-B3, G1-G3, and R1-R3. These compounds emit blue, green, and
      orange-red light, respectively, and show a red-shifted emission in the solid
      state relative to that in solution. The extent of the shift is highly dependent
      on the nature and the positions of the substituents. A red-shift as high as 120
      nm can be achieved by a suitable substitution, especially by N-substitution of
      carbazole. The presence of a carbaldehyde or malononitrile group on the carbazole
      moiety is found to quench fluorescence severely in solution and in the solid
      state, as indicated by low fluorescence quantum yields of B1 (phi(F)
      approximately 0.03), B3 (phi(F) approximately 0.04), and G1-G3 (phi(F)
      approximately 0.04-0.15). However, the effect is not the same for the
      fluorescence lifetime (tau(F) approximately 1-5.69 ns). The rate constants of
      radiative and nonradiative deactivation of B1-R3 have been found to be in the
      range of 6.40 x 10(6) to 9.50 x 10(8) and 1.38 x 10(8) to 9.84 x 10(8),
      respectively. Lowering the temperature from 25 to -10 degrees C causes a small
      but distinct red-shift in the emissions and a systematic increase in the phi(F)
      values of the blue and green emitters. Solvatochromism and concentration
      dependent emissions of the compounds are also discussed.

PMID- 19388715
TI  - S(N)2-type nucleophilic opening of beta-thiolactones (thietan-2-ones) as a source
      of thioacids for coupling reactions.
AB  - Beta-thiolactones monosubstituted in the 3-position by alkyl and carbamoyl groups
      undergo nucleophilic ring opening by arenethiolates through a process involving
      an S(N)2-type attack at the 4-position leading to 3-arylthiopropionates
      substituted in the 2-position. These thiocarboxylates can be trapped in situ by
      Mukaiyama's reagent or Sanger's reagent through a nucleophilic aromatic
      substitution process leading to highly activated thioesters that are then allowed
      to react further with primary or secondary amines leading, overall, to one-pot,
      three-component syntheses of 3-arylthiopropionamides carrying various
      substituents in the 2-position. Alternatively, the trapping combination of an
      electron deficient aryl halide and an amine may be replaced by a 2,4
      dinitrobenzenesulfonamide, resulting in the formation of the same products
      overall with the incorporation of the latent amine in the sulfonamide into the
      final amide product. In another embodiment, the thiocarboxylate intermediate is
      allowed to react with a sulfonyl azide, resulting overall in N-arenesulfonyl 3
      arylthiopropionamide derivatives.

PMID- 19388716
TI  - Waste-free synthesis of condensed heterocyclic compounds by rhodium-catalyzed
      oxidative coupling of substituted arene or heteroarene carboxylic acids with
      alkynes.
AB  - The direct oxidative coupling of 2-amino- and 2-hydroxybenzoic acids with
      internal alkynes proceeds efficiently in the presence of a rhodium/copper
      catalyst system under air to afford the corresponding 8-substituted isocoumarin
      derivatives, some of which exhibit solid-state fluorescence. Depending on
      conditions, 4-ethenylcarbazoles can be synthesized selectively from 2
      (arylamino)benzoic acids. The oxidative coupling reactions of heteroarene
      carboxylic acids as well as aromatic diacids with an alkyne are also described.

PMID- 19388717
TI  - A ligand free and room temperature protocol for Pd-catalyzed Kumada-Corriu
      couplings of unactivated alkenyl phosphates.
AB  - Kumada-Corriu cross-couplings of nonactivated cyclic and acyclic vinyl phosphates
      with aryl magnesium reagents afforded a series of 1,1-disubtituted alkenes in
      good yields for most cases when the reactions were performed at room temperature
      with the simple palladium salt, PdCl(2), without the presence of phosphine
      ligands.

PMID- 19388718
TI  - The good old drugs!

PMID- 19388719
TI  - How do we safely treat depression in children, adolescents and young adults?
AB  - Increasing concerns about the safety and efficacy of antidepressant drugs for
      children, adolescents and young adults have been countered by claims that reduced
      prescribing of antidepressants may have dangerous consequences. This leaves
      clinicians unsure as to how to weigh up the evidence and apply it to their
      patients. This paper promotes an approach of evaluating the evidence in each
      study according to the importance of the outcomes being measured in that study.
      It finds that on important measures such as mortality, hospitalization and
      quality of life, the evidence is unfavourable for antidepressants in this
      population. Here, an approach is suggested that primary care physicians might
      adopt with their depressed young patients. Through a combination of 'watchful
      waiting' and physical and emotional rehabilitation, physicians can actively
      intervene without reliance on medication or psychotherapy.

PMID- 19388720
TI  - Bias in benefit-risk appraisal in older products: the case of buflomedil for
      intermittent claudication.
AB  - Benefit-risk assessment should be ongoing during the life cycle of a
      pharmaceutical agent. New products are subjected to rigorous registration laws
      and rules, which attempt to assure the availability and validity of evidence. For
      older products, bias in benefit-risk assessment is more likely, as a number of
      safeguards were not in place at the time these products were registered. This
      issue of bias in benefit-risk assessment of older products is illustrated here
      with an example: buflomedil in intermittent claudication. Data on efficacy were
      retrieved from a Cochrane systematic review. Data on safety were obtained by
      comparing the number of reports of serious adverse events and fatalities
      published in the literature with those reported in postmarketing surveillance
      databases. In the case of efficacy, the slim basis of evidence for the benefit of
      buflomedil is undermined by documented publication bias. In the case of safety,
      bias in reporting to international safety databases is illustrated by the
      discrepancy between the number of drug-related deaths published in the literature
      (20), the potentially drug-related deaths in the WHO database (20) and deaths
      attributed to buflomedil in the database of the international marketing
      authorization holder (11). In older products, efficacy cannot be evaluated
      without a thorough search for publication bias. For safety, case reporting of
      drug-related serious events and deaths in the literature remains a necessary
      instrument for risk appraisal of older medicines, despite the existence of
      postmarketing safety databases. The enforcement of efficient communication
      between healthcare workers, drug companies, national centres of
      pharmacovigilance, national poison centers and the WHO is necessary to ensure the
      validity of postmarketing surveillance reporting systems. Drugs considered
      obsolete because of unfavourable benefit-risk assessment should not be allowed to
      stay on the market.

PMID- 19388722
TI  - Vaccines and Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is the leading cause of acute flaccid paralysis in
      developed countries and is characterized by various degrees of weakness, sensory
      abnormalities and autonomic dysfunction. Although the underlying aetiology and
      pathophysiology of GBS are not completely understood, it is broadly believed that
      immune stimulation plays a role in its pathogenesis. Thus, since vaccines have an
      effect on the immune system it is biologically plausible that immunizations may
      be associated with subsequent GBS. The objective of this article is to review the
      current body of evidence that either supports or does not support a causal,
      rather than just temporal, association between various vaccines and GBS, and to
      provide an evidence-based review of this issue. The scope of the article includes
      published reports that, regardless of method of case ascertainment, appeared in
      peer-reviewed literature between 1950 and 2008. Our review indicates that, with
      rare exceptions, associations between vaccines and GBS have been only temporal.
      There is little evidence to support a causal association with most vaccines. The
      evidence for a causal association is strongest for the swine influenza vaccine
      that was used in 1976-77. Studies of influenza vaccines used in subsequent years,
      however, have found small or no increased risk of GBS. Older formulations of
      rabies vaccine cultured in mammalian brain tissues have been found to have an
      increased risk of GBS, but newer formulations of rabies vaccine, derived from
      chick embryo cells, do not appear to be associated with GBS at a greater than
      expected rate. In an earlier review, the Institute of Medicine concluded that the
      evidence favoured a causal association between oral polio vaccine and tetanus
      toxoid-containing vaccines and GBS. However, recent evidence from large
      epidemiological studies and mass immunization campaigns in different countries
      found no correlation between oral polio vaccine or tetanus toxoid-containing
      vaccines and GBS. Spontaneous reports to the US Vaccine Adverse Events Reporting
      System shortly after the introduction of quadrivalent conjugated meningococcal
      vaccine (MCV4) raised concerns of a possible association with GBS. Comparisons
      with expected rates of GBS, however, were inconclusive for an increased risk, and
      lack of controlled epidemiological studies makes it difficult to draw conclusions
      about a causal association. For other vaccines, available data are based on
      isolated case reports or very small clusters temporally related to immunizations,
      and no conclusion about causality can be drawn. There are certain circumstances
      in which immunizing individuals, particularly those with a prior history of GBS,
      may require caution. However, the benefit of vaccines in preventing disease and
      decreasing morbidity and mortality, particularly for influenza, needs to be
      weighed against the potential risk of GBS.

PMID- 19388721
TI  - Managing epilepsy in women of childbearing age.
AB  - Epilepsy affects the menstrual cycle, aspects of contraception, fertility,
      pregnancy and bone health in women. It is common for seizure frequency to vary
      throughout the menstrual cycle. In ovulatory cycles, two peaks can be seen around
      the time of ovulation and in the few days before menstruation. In anovulatory
      cycles, there is an increase in seizures during the second half of the menstrual
      cycle. There is also an increase in polycystic ovaries and hyperandrogenism
      associated with valproate therapy. There are no contraindications to the use of
      non-hormonal methods of contraception in women with epilepsy. Non-enzyme-inducing
      antiepileptic drugs (AEDs) [valproate, benzodiazepines, ethosuximide,
      levetiracetam, tiagabine and zonisamide] do not show any interactions with the
      combined oral contraceptive (OC). There are interactions between the combined OC
      and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine,
      topiramate [dosages>200 mg/day], oxcarbazepine) and lamotrigine. Pre-conception
      counselling should be available to all women with epilepsy who are considering
      pregnancy. Women with epilepsy should be informed about issues relating to the
      future pregnancy, including methods and consequences of prenatal screening,
      fertility, genetics of their seizure disorder, teratogenicity of AEDs, folic acid
      and vitamin K supplements, labour, breast feeding and care of a child. During
      pregnancy, the lowest effective dose of the most appropriate AED should be used,
      aiming for monotherapy where possible. Recent pregnancy databases have suggested
      that valproate is significantly more teratogenic than carbamazepine, and the
      combination of valproate and lamotrigine is particularly teratogenic. Most
      pregnancies in women with epilepsy are without complications, and the majority of
      infants are delivered healthy with no increased risk of obstetric complications
      in women. There is no medical reason why a woman with epilepsy cannot breastfeed
      her child. The AED concentration profiled in breast milk follows the plasma
      concentration curve. The total amount of drug transferred to infants via breast
      milk is usually much smaller than the amount transferred via the placenta during
      pregnancy. However, as drug elimination mechanisms are not fully developed in
      early infancy, repeated administration of a drug such as lamotrigine via breast
      milk may lead to accumulation in the infant. Studies have suggested that women
      with epilepsy are at increased risk of fractures, osteoporosis and osteomalacia.
      No studies have been undertaken looking at preventative therapies for these co
      morbidities.

PMID- 19388723
TI  - Paediatric atypical antipsychotic monitoring safety (PAMS) study: pilot study in
      children and adolescents in secondary- and tertiary-care settings.
AB  - BACKGROUND: In the UK, treatment with antipsychotic medications for children is
      usually initiated by specialists in secondary care. Recent studies have shown an
      increase in the prescribing of atypical antipsychotics in children. The severity
      of possible adverse effects to antipsychotics in adults has lead to awareness of
      the importance of investigating the potential adverse effects of these agents in
      children. Additionally, there have been many reports proposing that the newer
      atypical antipsychotics are associated with many of the same adverse effects seen
      with the older generation drugs in children. The aim of the Paediatric Atypical
      Antipsychotic Monitoring Safety (PAMS) study was to determine the feasibility of
      conducting a prospective targeted pharmacovigilance study to monitor adverse drug
      reactions (ADRs) associated with atypical antipsychotic therapy in children seen
      in secondary- and tertiary-care settings. METHODS: Participants were identified
      from the clinical members of the UK Paediatric Psychopharmacology Groups in
      London and the West Midlands. Participating clinicians reported the number of
      patients (aged<or=18 years) taking atypical antipsychotic treatment who were
      under their care and any reportable ADRs experienced by these patients during the
      period September 2006-September 2007. Participants contributed data via password
      protected online data collection forms. RESULTS: A total of 35 clinicians
      consented to participate in the study. However, data from 22 of the participating
      clinicians were excluded because of incomplete reporting. Data from the remaining
      13 (37%) clinicians were eligible for the final analysis. There were 281 patients
      who received atypical antipsychotic treatment under the care of the 13
      participating clinicians. From these 281 patients, 40 ADR reports (0.14 ADR
      reports per patient; 95% CI 0.10, 0.19) from 37 patients were entered into the
      database. Of the 37 patients, 13 experienced more than one ADR, bringing the
      total number of ADRs to 56 (0.20 ADR per patient; 95% CI 0.15, 0.25). The most
      commonly reported ADRs were weight gain, extrapyramidal symptoms and
      hyperprolactinaemia. Rare ADRs, including neuroleptic malignant syndrome, were
      also reported. The durations of atypical antipsychotic drug exposure were
      recorded for 54 of the 56 ADRs reported. The median duration of exposure was 42
      days (interquartile range 23.25-90 days). CONCLUSIONS: Our study demonstrates
      that a clinician-based targeted pharmacovigilance study on atypical
      antipsychotics in children provides useful qualitative data. However, this pilot
      study raised many methodological issues, which should be addressed for the study
      to be extended nationally. Specifically, significant funding is needed to improve
      the reporting rate and the overall data obtained. Furthermore, the study yielded
      a very high incidence of serious ADRs, thus supporting the need for a larger and
      improved pharmacovigilance study to evaluate the safety of atypical
      antipsychotics in children.

PMID- 19388724
TI  - Iatrogenic effects of COX-2 inhibitors in the US population: findings from the
      Medical Expenditure Panel Survey.
AB  - BACKGROUND: Selective cyclo-oxygenase 2 inhibitors ('coxibs') have been
      demonstrated to increase cardiovascular risk, but the cumulative burden of
      adverse effects in the US population is uncertain. OBJECTIVE: To quantify
      cardiovascular and gastrointestinal (GI) haemorrhage disease burden from coxibs
      and traditional 'non-selective' non-steroidal anti-inflammatory drugs (t-NSAIDs)
      in the US population. DESIGN, SETTING AND PARTICIPANTS: Adult respondents from
      the 1999-2003 Medical Expenditure Panel Survey, a representative sample of the US
      population which first became available in December 2006, were included.
      Respondents were followed for 2 years. Exposure was defined by two or more
      prescriptions of rofecoxib, celecoxib or a t-NSAID in the first year. MAIN
      OUTCOME MEASURES: Acute myocardial infarction (AMI), stroke and/or GI haemorrhage
      in the year following exposure. RESULTS: Exposure to rofecoxib was associated
      with an adjusted odds ratio (OR) of 3.30 for AMI (95% CI 1.41, 7.68; p=0.01) and
      4.28 for GI haemorrhage (95% CI 1.33, 13.71; p=0.02). Celecoxib was not
      associated with a statistically significant effect on AMI (OR 1.44; 95% CI 0.57,
      3.69; p=0.44), but there was an OR of 2.43 for stroke (95% CI 1.05, 5.58; p=0.04)
      and 4.98 for GI haemorrhage (95% CI 2.22, 11.17; p<0.001). The group of t-NSAIDs
      was not associated with a significant adverse effect on AMI (OR 1.47; 95% CI
      0.76, 2.84; p=0.25) or stroke (OR 1.26; 95% CI 0.42, 3.81; p=0.68), and was
      associated with an OR of 2.38 for GI haemorrhage (CI 1.04, 5.46; p=0.04). In the
      1999-2004 period rofecoxib was associated with 46 783 AMIs and 31 188 GI
      haemorrhages; celecoxib with 21 832 strokes and 69 654 GI haemorrhages; resulting
      in an estimated 26 603 deaths from both coxibs. The t-NSAID group was associated
      with an excess of 87 327 GI haemorrhages and 9606 deaths in the same period.
      CONCLUSIONS: Iatrogenic effects of coxibs in the US population were substantial,
      posing an important public health risk. Drugs that were rapidly accepted for
      assumed safety advantages proved instead to have caused substantial injury and
      death.

PMID- 19388726
TI  - Spontaneous reports and pharmacogenetics: the role of the pharmacovigilance
      centre.

PMID- 19388725
TI  - Adverse drug reactions to local anaesthetics: a review of the French
      pharmacovigilance database.
AB  - BACKGROUND: Some evidence of significant patient morbidity or mortality has been
      reported with the use of local anaesthetics (LAs). The most common adverse drug
      reactions (ADRs) to LAs are neurological (seizures) and cardiac (conduction
      disorders, cardiac arrests). However, little is known about other adverse drug
      reactions (ADRs). OBJECTIVE: The aim of this study was to characterize the safety
      profile of the LAs lidocaine, bupivacaine, mepivacaine, ropivacaine and
      levobupivacaine. STUDY DESIGN: We studied ADRs occurring between 1995 and 2006
      reported to the French Pharmacovigilance System. MAIN OUTCOME MEASURE: For each
      ADR, we noted type of LA, type of ADR, its seriousness and the causality
      assessment score. RESULTS: We identified 727 reports (corresponding to 0.3% of
      patients in the database) in which LA was suspected as the cause of 1157
      different ADRs. Sixty-one patients (8.7%) were children aged<18 years. Lidocaine
      (36.0%) and bupivacaine (35.4%) were the LAs most often involved. The most
      frequently reported ADRs were failure of the block (27.7%), followed by
      neurological (22.1%), allergic (19.4%) and cardiovascular (15.3%) complications.
      Eight patients died. Spinal anaesthesia performed with bupivacaine represented
      90% of failed blocks. Seizures were the most frequent neurological complications,
      leading to death in four cases. Twenty-two of 111 cardiovascular complications
      were cardiac arrest (three of which were fatal). CONCLUSION: To our knowledge,
      this is the first analysis of safety profiles of LAs in a non-selected
      population, using data collected in a pharmacovigilance database. The present
      study confirmed the frequency and seriousness of both neurological and
      cardiovascular complications. Other less well documented ADRs were identified,
      such as spinal anaesthesia failures with bupivacaine and allergic reactions
      following LA injections.

PMID- 19388727
TI  - Using He droplets for measurements of interconversion enthalpy of conformers in 2
      chloroethanol.
AB  - 2-chloroethanol molecules having temperature from 300 to 600 K have been captured
      by helium droplets and the infrared spectra of the O-H and C-H stretching bands
      of the embedded molecules have been obtained. The intensity ratio of the bands
      due to trans and gauche conformers of the molecules follows the Arrhenius
      dependence, giving the enthalpy of conformers interconversion of 1.1 kcal/mol. It
      is concluded that the abundance ratio of the conformers, which are at equilibrium
      in the gas phase, remains unchanged upon the rapid cooling of the molecules in
      the helium droplets.

PMID- 19388728
TI  - Experimental evidence for the role of the pi(CO)* orbital in electron transfer to
      gas phase acetic acid CH3CO2H: effects of molecular orientation.
AB  - Electron transfer from K atoms to oriented acetic acid molecules produces acetate
      ions (and K(+)) when the CO(2)H end of the molecule is attacked. The electron
      enters the pi(CO)(*) orbital and the donor atom distorts the molecule to allow
      migration to the sigma(OH)(*) orbital, thereby breaking the bond.

PMID- 19388730
TI  - Quantum densities of states of fluxional polyatomic systems from a superposition
      approximation.
AB  - The superposition method is used to calculate quantum densities of states of
      polyatomic systems with multiple isomeric structures. For each isomer,
      anharmonicities are included rigorously using a Dunham expansion of the
      vibrational energy levels and short exchange Monte Carlo simulations are used to
      compute the individual quantum densities of states. The method is applied to the
      computation of thermodynamical properties of the Ar(13) and Ne(13) clusters. The
      canonical heat capacities are found in very satisfactory agreement with the
      predictions of quantum or semiclassical sampling methods.

PMID- 19388729
TI  - The stochastic separatrix and the reaction coordinate for complex systems.
AB  - We present a new approach to the identification of degrees of freedom which
      comprise a reaction coordinate in a complex system. The method begins with the
      generation of an ensemble of reactive trajectories. Each trajectory is analyzed
      for its equicommittor position or transition state; then the transition state
      ensemble is identified as the stochastic separatrix. Numerical analysis of the
      points along the separatrix for variability of coordinate location correctly
      identifies the components of the reaction coordinate in a test system of a double
      well coupled to a promoting vibration and a bath of linearly coupled oscillators.

PMID- 19388731
TI  - On the relation between time-dependent and variational density functional theory
      approaches for the determination of excitation energies and transition moments.
AB  - It is shown that it is possible to derive the basic eigenvalue equation of
      adiabatic time-dependent density functional theory within the Tamm-Dancoff
      approximation (TD-DFT/TD) from a variational principle. The variational principle
      is applied to the regular Kohn-Sham formulation of DFT energy expression for a
      single Slater determinant and leads to the same energy spectrum as TD-DFT/TD. It
      is further shown that this variational approach affords the same electric and
      magnetic transition moments as TD-DFT/TD. The variational scheme can also be
      applied without the Tamm-Dancoff approximation. Practical implementations of TD
      DFT are limited to second order response theory which introduces errors in
      transition energies for charge transfer and Rydberg excitations. It is indicated
      that higher order terms can be incorporated into the variational approach. It is
      also discussed how the current variational method is related to traditional DFT
      schemes based on variational principles such as DeltaSCF-DFT, and how they can be
      combined.

PMID- 19388732
TI  - General theory of excitation energy transfer in donor-mediator-acceptor systems.
AB  - General theory of the excitation energy transfer (EET) in the case of donor
      mediator-acceptor system was constructed by using generalized master equation
      (GME). In this theory, we consider the direct and indirect transitions in the EET
      consistently. Hence, our theory includes the quantum mechanical interference
      between the direct and indirect transitions automatically. Memory functions in
      the GME were expressed by the overlap integrals among the time-dependent emission
      spectrum of the donor, the absorption spectrum of the mediator, the time
      dependent emission spectrum of the mediator, and the absorption spectrum of the
      acceptor. In the Markov limit of the memory functions, we obtained the rate of
      EET which consists of three terms due to the direct transition, the indirect
      transition, and the interference between them. We found that the interference
      works effectively in the limit of slow thermalization at the intermediate state.
      The formula of EET rate in this limit was expressed by the convolution of the EET
      interaction and optical spectra. The interference effect strongly depends on the
      width of the absorption spectrum of mediator molecule and the energy gap between
      the donor and the mediator molecules.

PMID- 19388733
TI  - An electron-preceding perspective on the deformation of materials.
AB  - Elements of Bader's theory of atoms in molecules are combined with density
      functional theory to provide an electron-preceding perspective on the deformation
      of materials. From this perspective, a network of atoms is changed by moving the
      bonds that connect them; the nuclei then follow. The electronic stress tensor is
      the key to understanding this process. Eigenvectors of the electronic stress
      tensor at critical points of the electron density provide insight into the
      "normal electronic modes" that accompany structural dynamics and rearrangements.
      Eigenvectors of the second-derivative matrix of the electron density emerge as
      effective approximations to the eigenvectors of the stress tensor; this makes it
      possible to apply our results to experimentally and computationally determined
      electron densities. To demonstrate the usefulness of our analysis, we show that
      (a) the low-frequency modes of ice Ic can be predicted from the eigenvectors of
      the second-derivative matrix and (b) the eigenvectors of the second-derivative
      matrix are associated with the direction of structural change during the pressure
      induced phase transition from ice XI to a ferroelectric ice VIII-like structure.
      We conclude that the eigenvectors of the second-derivative matrix of the electron
      density are the key ingredient for constructing a dynamical theory of atoms in
      molecules.

PMID- 19388734
TI  - Ab initio calculation of the electronic structures of the (7)Sigma+ ground and A
      (7)Pi and a (5)Sigma+ excited states of MnH.
AB  - Electronic structures and molecular constants of the ground (7)Sigma(+) and low
      lying A (7)Pi and a (5)Sigma(+) electronic excited states of the MnH molecule
      were studied by multireference single and double excitation configuration
      interaction (MR-SDCI) with Davidson's correction (+Q) calculations under exact
      C(infinity v) symmetry using Slater-type basis sets. To correctly describe the
      (7)Sigma(+) electronic ground state, X (7)Sigma(+), at the MR-SDCI+Q calculation,
      we employed a large number of reference configurations in terms of the state
      averaged complete active space self-consistent field (CASSCF) orbitals, taking
      into account the contribution from the B (7)Sigma(+) excited state. The A (7)Pi
      and a (5)Sigma(+) states can well be described by the MR-SDCI wave functions
      based on the CASSCF orbitals obtained for the lowest state only. In the MR
      SDCI+Q, calculations of the X (7)Sigma(+), A (7)Pi, and a (5)Sigma(+) states
      required 16, 7, and 17 reference configurations, respectively. Molecular
      constants, i.e., r(e) and omega(e) of these states and excitation energy from the
      X (7)Sigma(+) state, obtained at the MR-SDCI+Q level, showed a good agreement
      with experimental values. The small remaining differences may be accounted for by
      taking relativistic effects into account.

PMID- 19388735
TI  - Calculating electron paramagnetic resonance g-matrices for triplet state
      molecules from multireference spin-orbit configuration interaction wave
      functions.
AB  - We present a way to calculate electron paramagnetic resonance (EPR) g-matrices
      from variationally optimized spin-orbit coupled wave functions. Our method
      constructs a triangular g-matrix from the matrix representation of the total
      electron magnetic moment in the basis of the spin-orbit coupled wave functions by
      means of a projection technique. Principal g-values are obtained in the standard
      fashion by forming from the triangular matrix g the tensor G=gg(t) and
      diagonalizing it. In principle, the scheme allows to calculate the spin-orbit
      orbital Zeeman cross term which usually gives the dominating contribution to the
      EPR g-shifts for any multiplicity. We have implemented this approach into a
      multireference spin-orbit configuration interaction (MRSOCI) program [M.
      Kleinschmidt et al., J. Chem. Phys. 124, 124101 (2006)]. Test applications are
      carried out for various triplet state sytems. The g-shifts of several of main
      group diatomics with X (3)Sigma(g)(-) ground state are investigated at the level
      of ab initio MRSOCI. We obtain perpendicular g-shifts which underestimate
      experimental Delta g(perpendicular) values from literature by approximately 13%
      on the average. For a set of organic triplet state molecules we employ the
      combined density functional theory/multireference configuration interaction
      (DFT/MRCI) technique [S. Grimme and M. Waletzke, J. Chem. Phys. 111, 5645 (1999)]
      to reduce the computational costs of the spin-free correlation problem. This
      approach yields principal g-values that match experiment well in many cases. Due
      to the small absolute g-shifts, a rigorous comparison will require the inclusion
      of first-order contributions such as the relativistic mass correction and gauge
      correction terms which have not been included here. For the triplet state
      dication trans-(CNSSS)(2)(2+) the principal g-shifts Delta g(a)=-0.3 ppt, Delta
      g(b)=17.5 ppt, and Delta g(c)=26.6 ppt are significantly larger and compare
      rather well to the experimental values Delta g(1)=-0.1+/-0.2 ppt, Delta
      g(2)=14.8+/-0.2 ppt, and Delta g(3)=24.8+/-0.1 ppt [A. Berces et al., Magn.
      Reson. Chem. 37, 353 (1999)]. In comparison to conventional truncated sum-over
      state techniques based on Rayleigh-Schrodinger perturbation theory, our new
      variational approach shows, in practice, robust and advantageous convergence
      characteristics with respect to the size of the many-particle basis set. We
      demonstrate that the DFT/MRSOCI technology is a very feasible means to compute
      reliable g-shifts for large organic triplet systems at low computational cost.

PMID- 19388736
TI  - Atomic Cholesky decompositions: a route to unbiased auxiliary basis sets for
      density fitting approximation with tunable accuracy and efficiency.
AB  - Cholesky decomposition of the atomic two-electron integral matrix has recently
      been proposed as a procedure for automated generation of auxiliary basis sets for
      the density fitting approximation [F. Aquilante et al., J. Chem. Phys. 127,
      114107 (2007)]. In order to increase computational performance while maintaining
      accuracy, we propose here to reduce the number of primitive Gaussian functions of
      the contracted auxiliary basis functions by means of a second Cholesky
      decomposition. Test calculations show that this procedure is most beneficial in
      conjunction with highly contracted atomic orbital basis sets such as atomic
      natural orbitals, and that the error resulting from the second decomposition is
      negligible. We also demonstrate theoretically as well as computationally that the
      locality of the fitting coefficients can be controlled by means of the
      decomposition threshold even with the long-ranged Coulomb metric. Cholesky
      decomposition-based auxiliary basis sets are thus ideally suited for local
      density fitting approximations.

PMID- 19388737
TI  - Interfacial tension of nonassociating pure substances and binary mixtures by
      density functional theory combined with Peng-Robinson equation of state.
AB  - We develop a density functional theory and investigate the interfacial tension of
      several pure substances N(2), CO(2), H(2)S, normal alkanes from C(1) to nC(10),
      and binary mixtures C(1)/C(3), C(1)/nC(5), C(1)/nC(7), C(1)/nC(10), CO(2)/nC(4),
      N(2)/nC(5), N(2)/nC(6), N(2)/nC(8), N(2)/nC(10), nC(6)/nC(7), nC(6)/nC(8), and
      nC(6)/nC(10). The theory is combined with the semiempirical Peng-Robinson
      equation of state (PR-EOS). The weighted density approximation (WDA) is adopted
      to extend the bulk excess Helmholtz free energy to the inhomogeneous interface.
      Besides, a supplementary term, quadratic density expansion (QDE), is introduced
      to account for the long-range characteristic of intermolecular dispersion
      attractions, which cannot be accurately described by the WDA. In the bulk limit,
      the QDE vanishes and the theory is reduced to the PR-EOS. For pure substances,
      the potential expansion parameter is the only adjustable parameter in the QDE and
      determined by using a single measured interfacial tension at the lowest
      temperature examined. Then without any parameter adjustment, we faithfully
      predict the interfacial tensions of pure substances and mixtures over a wide
      range of conditions.

PMID- 19388738
TI  - Quasilinearity in tetratomic molecules: an ab initio study of the CHNO family.
AB  - We present coupled-cluster CCSD(T) all electron results for the equilibrium
      structure of isofulminic acid, HONC, together with results for the barrier to
      linearity and the energetics for the four most stable members of the CHNO isomer
      family, obtained for the ground electronic states by means of large correlation
      consistent basis sets. Minimum energy paths along the angular coordinates
      reported for these CHNO isomers are combined with the dominant kinetic energy
      contributions to predict key rovibrational spectroscopic features which are
      clearly reminiscent of quasilinear behavior in tetratomic molecules.

PMID- 19388739
TI  - A one-dimensional dipole lattice model for water in narrow nanopores.
AB  - We present a recently developed one-dimensional dipole lattice model that
      accurately captures the key properties of water in narrow nanopores. For this
      model, we derive three equivalent representations of the Hamiltonian that
      together yield a transparent physical picture of the energetics of the water
      chain and permit efficient computer simulations. In the charge representation,
      the Hamiltonian consists of nearest-neighbor interactions and Coulomb-like
      interactions of effective charges at the ends of dipole ordered segments.
      Approximations based on the charge picture shed light on the influence of the
      Coulomb-like interactions on the structure of nanopore water. We use Monte Carlo
      simulations to study the system behavior of the full Hamiltonian and its
      approximations as a function of chemical potential and system size and
      investigate the bimodal character of the density distribution occurring at small
      system sizes.

PMID- 19388740
TI  - A theoretical investigation on the spectrum of the Ar trimer for high rotational
      excitations.
AB  - A detailed study of the rovibrational spectrum of the Ar trimer is performed by
      means of an exact hyperspherical coordinate (HC) method and a variational
      approach based on distributed Gaussian functions (DGFs) to describe the
      interparticle distances. The good agreement observed between the energy levels
      obtained with both procedures for high values of the total angular momentum (J=15
      and 20) reveals the quality of the DGF method to describe the rotation of the
      title system. Rotational constants for the lowest bound states, obtained as
      averages for each vibrational state, have been obtained and compared to previous
      results. A detailed analysis of density probability functions obtained by means
      of the HC approach for rovibrational states at J=0 and 20 shows close similitudes
      thus supporting the vibration-rotation separation adopted within the DGF scheme
      for the Ar(3) system.

PMID- 19388741
TI  - Reversible structure transformation in ice nanocluster.
AB  - Water freezes to ice by cooling. Once ice is formed, the phase does not change
      unless heated over the melting point. This is a familiar phenomenon observed in
      our everyday life. Here, we demonstrate non-bulk-like behavior of nanosized ice
      by molecular-dynamics simulation using the TIP4P potential. Our 100 micros
      simulations reveal that the structure of the (H(2)O)(20) nanocluster reversibly
      changes and a variety of solidlike phases, such as bilayer structures composed of
      three pentagonal prisms, square and pentagonal ice nanotubes, and stuffed
      fullerenelike (H(2)O)@(H(2)O)(19) structures, dynamically coexists even at 52% of
      the bulk melting point.

PMID- 19388742
TI  - The water-benzene interaction: insight from electronic structure theories.
AB  - Weak noncovalent interactions such as van der Waals and hydrogen bonding are
      ubiquitous in nature, yet their accurate description with electronic structure
      theories is challenging. Here we assess the ability of a variety of theories to
      describe a water-benzene binding energy curve. Specifically, we test Hartree
      Fock, second-order Moller-Plesset perturbation theory, coupled cluster, density
      functional theory with several exchange-correlation functionals with and without
      empirical vdW corrections, and quantum Monte Carlo (QMC). Given the relative
      paucity of QMC reports for noncovalent interactions, it is interesting to see
      that QMC and coupled cluster with single, double, and perturbative triple
      excitations [CCSD(T)] are in very good agreement for most of the binding energy
      curve, although at short distances there are small deviations on the order of 20
      meV.

PMID- 19388743
TI  - Structures of water-CO2 and methanol-CO2 cluster ions: [H2O x (CO2)n]+ and [CH3OH
      x (CO2)n]+ (n = 1-7).
AB  - Infrared photodissociation (IRPD) spectra of [H(2)O x (CO(2))(n)](+) and [CH(3)OH
      x (CO(2))(n)](+) (n=1-7) are measured in the 1100-3800 cm(-1) region. At the same
      time, the solvation characteristics in the clusters are investigated
      theoretically; the geometry optimization and the vibrational analysis are carried
      out for the [H(2)O x (CO(2))(n)](+) (n=1-4) and the [CH(3)OH x (CO(2))(n)](+)
      (n=1-3) ions at the MP2/6-31+G(*) level of theory. The IRPD spectrum of the
      [H(2)O x (CO(2))(1)](+) ion shows the free OH and the hydrogen-bonded OH
      stretching bands of the H(2)O(+) ion core and the antisymmetric CO stretching
      band of the solvent CO(2) molecule, indicating that the solvent CO(2) molecule is
      preferentially solvated to the H(2)O(+) ion core via the O-H...OCO hydrogen bond.
      In [H(2)O x (CO(2))(2)](+), the free OH stretching band is not observed; both of
      the OH groups of the H(2)O(+) ion core are hydrogen bonded to the solvent CO(2)
      molecules. Spectral features of the IRPD spectra of [H(2)O x (CO(2))(n)](+) (n=3
      7) suggest that the third and the fourth CO(2) molecules are bound to the oxygen
      atom of the H(2)O(+) ion core, and that the first solvation shell of the H(2)O(+)
      ion core becomes filled with four CO(2) molecules. All the IRPD spectra of the
      [CH(3)OH x (CO(2))(n)](+) (n=1-7) ions display the hydrogen-bonded OH stretching
      band of the CH(3)OH(+) ion core, meaning that the solvent CO(2) molecule is
      preferentially bonded to the OH group of the CH(3)OH(+) ion core, similar to the
      case of [H(2)O x (CO(2))(n)](+). Quantum chemical calculations for the [CH(3)OH x
      (CO(2))(1-3)](+) ions demonstrate that the second and the third solvent CO(2)
      molecules are bonded to the oxygen atom of the CH(3)OH(+) ion core.

PMID- 19388744
TI  - Ultrafast electron dynamics following outer-valence ionization: the impact of low
      lying relaxation satellite states.
AB  - Low-lying relaxation satellites give rise to ultrafast electron dynamics
      following outer-valence ionization of a molecular system. To demonstrate the
      impact of such satellites, the evolution of the electronic cloud after sudden
      removal of an electron from the highest occupied molecular orbital (HOMO) of the
      organic unsaturated nitroso compound 2-nitroso[1,3]oxazolo[5,4-d][1,3]oxazole is
      traced in real time and space using ab initio methods only. Our results show that
      the initially created hole charge remains stationary but on top of it the system
      reacts by an ultrafast pi-pi(*) excitation followed by a cyclic excitation-de
      excitation process which leads to a redistribution of the charge. The pi-pi(*)
      excitation following the removal of the HOMO electron takes place on a
      subfemtosecond time scale and the period of the excitation-de-excitation
      alternations is about 1.4 fs. In real space the processes of excitation and de
      excitation represent ultrafast delocalization and localization of the charge. The
      results are analyzed by simple two- and three-state models.

PMID- 19388746
TI  - Nuclear dynamics during the resonant Auger decay of water molecules.
AB  - The resonant Auger decay of water molecules is investigated. Here, the excitation
      process, the motion of the nuclei, and the decay of the resonantly excited state
      take place on the same (femtosecond) time scale. Therefore, a multistep picture
      is not suitable. Instead, the nuclear wave packet at each instant of time is a
      result of several competing and interfering contributions. The resonant Auger
      decay of water is simulated and its dynamics is studied in detail. An analysis of
      the final vibrational distribution is given. The multiconfiguration time
      dependent Hartree method is used to study the intricate multidimensional
      dynamics. The potential energy surfaces have been calculated using a
      multireference configuration interaction method.

PMID- 19388745
TI  - Synchrotron photoionization mass spectrometry study of intermediates in fuel-rich
      1,2-dimethoxyethane flame.
AB  - Intermediates in a fuel-rich premixed laminar 1,2-dimethoxyethane (DME) flame are
      studied by molecular beam mass spectrometry combined with tunable synchrotron
      vacuum ultraviolet photoionization. About 30 intermediate species are identified
      in the present work, and their mole fraction profiles are evaluated. The
      experimental results show that the formations of intermediates, both hydrocarbons
      and oxygenated hydrocarbons, are closely linked to the structure of fuel, which
      is consistent with the previous reports. Species produced from H atom abstraction
      and beta scission of DME usually have much higher concentrations than others. The
      oxygen atoms in DME are considered to act as partitions of the primary
      intermediates; therefore farther reactions among these primary intermediates are
      difficult to occur, resulting in absence of most large intermediate species.

PMID- 19388748
TI  - Valence-bond description of chemical reactions on Born-Oppenheimer molecular
      dynamics trajectories.
AB  - The nature of chemical bonds on dynamic paths was investigated using the complete
      active space valence-bond (CASVB) method and the Born-Oppenheimer dynamics. To
      extract the chemical bond picture during reactions, a scheme to collect
      contributions from several VB (resonance) structures into a small numbers of
      indices was introduced. In this scheme, a tree diagram for the VB structures is
      constructed with the numbers of the ionic bonds treated as generation. A pair of
      VB structures is related to each other if one VB structure is transferred into
      the other by changing a covalent bond to an ionic bond. The former and latter VB
      structures are named parent and child structures, respectively. The weights of
      the bond pictures are computed as the sum of the CASVB occupation numbers running
      from the top generation to the bottom along the descent of the VB structures.
      Thus, a number of CASVB occupation numbers are collected into a small number of
      indices, and a clear bond picture may be obtained from the CASVB wave function.
      The scheme was applied to the hydrogen exchange reaction H(2)+F-->H+HF and the
      Diels-Alder reaction C(5)H(6)(cyclopentadiene)+CH(2)=CH(2)(ethylene)-
      >C(7)H(10)(norbornene). In both the reactions, the scheme gave a clear picture
      for the Born-Oppenheimer dynamics trajectories. The reconstruction of the bonds
      during reactions was well described by following the temporal changes in weight.

PMID- 19388747
TI  - The electronic structure and bonding of AlNAl.
AB  - We have studied 16 states, 7 doublets, and 9 quartets of the AlNAl isomer mainly
      through multireference methods and correlation consistent basis sets. We report
      equilibrium geometries, energetics, and dipole moments, whereas for a number of
      low lying states we have constructed dissociation AlN-Al potential energy
      profiles. For the same states we also analyze their bonding character using
      valence-bond-Lewis diagrams. Our results are consistent with the limited
      experimental data.

PMID- 19388749
TI  - Field-free molecular alignment for studies using x-ray pulses from a synchrotron
      radiation source.
AB  - A short, intense laser pulse may be employed to create a spatially aligned
      molecular sample that persists after the laser pulse is over. We theoretically
      investigate whether this impulsive molecular alignment technique may be exploited
      for experiments using x-ray pulses from a third-generation synchrotron radiation
      facility. Using a linear rigid rotor model, the alignment dynamics of model
      molecular systems with systematically increasing size is calculated utilizing
      both a quantum density matrix formalism and a classical ensemble method. For each
      system, the alignment dynamics obtained for a 95 ps laser is compared with that
      obtained for a 10 ps laser pulse. The average degree of alignment after the laser
      pulse, as calculated quantum mechanically, increases with the size of the
      molecule. This effect is quantitatively reproduced by the classical calculations.
      The average degree of impulsive alignment is high enough to induce a pronounced
      linear dichroism in resonant x-ray absorption using the intense 100 ps x-ray
      pulses currently available. However, for structural studies based on elastic x
      ray scattering, bright x-ray pulses with a duration of 1 ps or shorter will be
      required in order to make full use of impulsive molecular alignment.

PMID- 19388750
TI  - The rotational spectrum of the FeD radical in its X (4)Delta state, measured by
      far-infrared laser magnetic resonance.
AB  - Transitions between the spin-rotational levels of the FeD radical in the v=0
      level of the X (4)Delta ground state have been detected by the technique of laser
      magnetic resonance at far-infrared wavelengths. Pure-rotational transitions have
      been observed for the three lowest spin components. Lambda-type doubling is
      resolved on all the observed transitions; nuclear hyperfine structure is not
      observed. The energy levels of FeD are strongly affected by the breakdown of the
      Born-Oppenheimer approximation and cannot be modeled accurately by an effective
      Hamiltonian. The data are therefore fitted to an empirical formula to yield term
      values and g-factors for the various spin-rotational levels involved.

PMID- 19388751
TI  - The photoelectron spectrum of the isopropoxide anion: nonadiabatic effects due to
      conical intersections and the spin-orbit interaction.
AB  - The negative ion photoelectron spectrum of the isopropoxide anion is determined
      using the multimode vibronic coupling approach. The simulated spectrum is based
      on a two state quasidiabatic Hamiltonian for the isopropoxy radical, H(d), which
      includes all terms through second-order order in all internal coordinates and
      accurately represents the vicinity of the ab initio determined equilibrium
      geometry of the ground electronic state as well as the minimum energy crossing
      point (MECP) on the symmetry-allowed (2)A(")-(2)A(') accidental seam of conical
      intersection. H(d) is centered at the (2)A(")-(2)A(') MECP and is determined from
      ab initio gradients and derivative couplings using a normal equations based
      algorithm. Spin-orbit effects are included using a generalization of a procedure
      due to Child and Longuet-Higgins. The nonadiabatic interactions coupling the
      (2)A(") and (2)A(') states are very similar to those found in an Exe Jahn-Teller
      system although the requisite symmetry is absent. The simulated photoelectron
      spectrum for isopropoxide-h(7) is compared to a measured photoelectron spectrum
      and the results of a dispersed fluorescence experiment on the isopropoxy radical.
      The nominal A (2)A-X (2)A splitting of 68 cm(-1) from the dispersed fluorescence
      experiment is confirmed. This splitting is shown to be a consequence of the
      accidental Jahn-Teller symmetry and the spin-orbit interaction so that the
      standard designation of this spectral feature as the A-X splitting is not
      appropriate. This spectral feature is better thought of as the spin-orbit
      splitting of a nearly degenerate ground state. It is further shown that the
      intensities and line positions are such that the origin band of the nominal A
      (2)A state and that of the X (2)A state could not be distinguished with the
      resolution available in the photoelectron experiment. The photoelectron spectrum
      of the completely deuterated analog, isopropoxide-d(7), is also reported and
      discussed.

PMID- 19388752
TI  - Theoretical study of the electronic states of CuCl2.
AB  - The electronic states of the CuCl(2) molecule are studied by several theoretical
      methods. We report geometries, excitation energies, vibrational frequencies,
      rotational constants, and transition dipole moments. With the purpose to describe
      the correlation energy accurately enough, a set of diffuse secondary 3d(')
      orbitals is introduced, thus resulting in a large active space of 21 electrons in
      17 orbitals. By restricting the active space and selecting dominant
      configurations, the results of the general multireference second-order
      perturbation theory with this large active space agree very well with the
      experimental ones. It is found that the so-called (2)Pi(u) state is asymmetric
      linear and the (2)Sigma(u)(+) state is bent at the minima on their adiabatic
      potential energy surfaces, whereas the other five gerade states are
      centrosymmetric linear. After including the spin-orbit coupling, the
      (I)(2)Pi(g3/2)-(I)(2)Pi(g1/2) splitting is computed to be 415 cm(-1), in
      excellent agreement with the experimental value of about 480 cm(-1).

PMID- 19388753
TI  - Structural study of the Eu3+ environments in fluorozirconate glasses: role of the
      temperature-induced and the pressure-induced phase transition processes in the
      development of a rare earth's local structure model.
AB  - The correlation between the optical properties of the Eu(3+) ions and their local
      structures in fluorozirconate glasses and glass-ceramics have been analyzed by
      means of steady-state and time-resolved site-selective laser spectroscopies.
      Changes in the crystal-field interaction, ranging from weak to medium strength
      values, are observed monitoring the luminescence and the lifetime of the Eu(3+)
      ions in different local environments in the glass. As key roles in this study,
      the Eu(3+) luminescence in the thermally-induced crystallization of the glass and
      the pressure-induced amorphization of the crystalline phase of the glass-ceramic
      experimentally states the existence of a parent local structure for the Eu(3+)
      ions in the glass, identified as the EuZrF(7) crystalline phase. Starting from
      the ab initio single overlap model, crystal-field calculations have been
      performed in the glass and the glass-ceramic. From the site-selective
      measurements, the crystal-field parameters sets are obtained, giving a suitable
      simulation of the (7)F(J) (J=0-6) Stark energy level diagram for the Eu(3+) ions
      in the different environments present in the fluorozirconate glass. A simple
      geometrical model based on a continuous distortion of the parent structure is
      proposed for the distribution of local environments of the Eu(3+) ions in the
      fluorozirconate glass.

PMID- 19388754
TI  - Solvent dependent structural perturbations of chemical reaction intermediates
      visualized by time-resolved x-ray diffraction.
AB  - Ultrafast time-resolved wide angle x-ray scattering from chemical reactions in
      solution has recently emerged as a powerful technique for determining the
      structural dynamics of transient photochemical species. Here we examine the
      structural evolution of photoexcited CH(2)I(2) in the nonpolar solvent
      cyclohexane and draw comparisons with a similar study in the polar solvent
      methanol. As with earlier spectroscopic studies, our data confirm a common
      initial reaction pathway in both solvents. After photoexcitation, CH(2)I(2)
      dissociates to form CH(2)I* + I*. Iodine radicals remaining within the solvent
      cage recombine with a nascent CH(2)I* radical to form the transient isomer CH(2)I
      I, whereas those which escape the solvent cage ultimately combine to form I(2) in
      cyclohexane. Moreover, the transient isomer has a lifetime approximately 30 times
      longer in the nonpolar solvent. Of greater chemical significance is the property
      of time-resolved wide angle x-ray diffraction to accurately determine the
      structure of the of CH(2)I-I reaction intermediate. Thus we observe that the
      transient iodine-iodine bond is 0.07 A+/-0.04 A shorter in cyclohexane than in
      methanol. A longer iodine-iodine bond length for the intermediate arises in
      methanol due to favorable H-bond interaction with the polar solvent. These
      findings establish that time-resolved x-ray diffraction has sufficient
      sensitivity to enable solvent dependent structural perturbations of transient
      chemical species to be accurately resolved.

PMID- 19388755
TI  - Femtosecond pump-probe studies of actinic-wavelength dependence in aqueous
      chlorine dioxide photochemistry.
AB  - The actinic or photolysis-wavelength dependence of aqueous chlorine dioxide
      (OClO) photochemistry is investigated using femtosecond pump-probe spectroscopy.
      Following photoexcitation at 310, 335, and 410 nm the photoinduced evolution in
      optical density is measured from the UV to the near IR. Analysis of the optical
      density evolution illustrates that the quantum yield for atomic chlorine
      production (Phi(Cl)) increases with actinic energy, with Phi(Cl)=0.16+/-0.02 for
      410 nm excitation and increasing to 0.25+/-0.01 and 0.54+/-0.10 for 335 and 310
      nm excitations, respectively. Consistent with previous studies, the production of
      Cl occurs through two channels, with one channel corresponding to prompt (<5 ps)
      Cl formation and the other corresponding to the thermal decomposition of ClOO
      formed by OClO photoisomerization. The partitioning between Cl production
      channels is dependent on actinic energy, with prompt Cl production enhanced with
      an increase in actinic energy. Limited evidence is found for enhanced ClO
      production with an increase in actinic energy. Stimulated emission and excited
      state absorption features associated with OClO populating the optically prepared
      (2)A(2) surface decrease with an increase in actinic energy suggesting that the
      excited-state decay dynamics are also actinic energy dependent. The studies
      presented here provide detailed information on the actinic-wavelength dependence
      of OClO photochemistry in aqueous solution.

PMID- 19388756
TI  - Bilayered smectic phase polymorphism in the dipolar Gay-Berne liquid crystal
      model.
AB  - We present computer simulations of the Gay-Berne model with a strong terminal
      dipole. We report the existence of different stable antiferroelectric
      interdigitated bilayered phases in this model with diverse in-plane organization.
      The occurrence of these phases depends crucially on the value of the molecular
      elongation kappa. For kappa=3 we find an interdigitated bilayered smectic-A phase
      (absent when there is no dipole) and a bilayered smectic-T (or crystal) with
      positional in-plane tetragonal ordering, different from the hexatic observed in
      the absence of the molecular dipole. For kappa=4, bilayered smectic-A and in
      plane hexatic-ordered smectic-B (or crystal) phases are observed.

PMID- 19388757
TI  - Mixing effects in glass-forming Lennard-Jones mixtures.
AB  - Mixing effects have been investigated from molecular dynamics simulations at
      constant number of particles, volume, and temperature on the Kob-Andersen glass
      forming Lennard-Jones atomic mixture A(x)B(1-x) for 0 < or = x < or = 1
      compositions. Upon cooling, crystallization is observed for x < or = 0.5 and x >
      or = 0.9 compositions. The crystalline states can be described by a quite complex
      coexistence of voids (x < or = 0.5), point defects, and one or two crystal
      structures which were characterized and found identical to those reported by
      Fernandez and Harrowell [Phys. Rev. E 67, 011403 (2003)] from energy
      minimization. Amorphization is also seen at 0.6 < or = x < or = 0.8 compositions
      and it is suggested that both crystal structures, CsCl and fcc-hcp, do not
      compete at these compositions since only one type of crystalline seed is found in
      the liquid, either fcc/hcp or CsCl. A significant decrease in the diffusion
      constants for both A and B particles is also seen above x(A) approximately = 0.5.
      The problem of the extraordinary stability of the model against crystallization
      is discussed.

PMID- 19388758
TI  - Orientational order of near D(3h) solutes in nematic liquid crystals.
AB  - Solutes that are similar in size, have a shape that is close to D(3h) symmetry
      but contain dissimilar substituent groups (methyl versus chloro, contributing
      different electrostatic interactions to the anisotropic intermolecular
      potential), are used to delineate the short- and long-range anisotropic
      intermolecular interactions that lead to solute orientational order in nematic
      liquid crystals. The short-range interactions should be similar for all solutes
      and for D(3h) symmetry should yield a single independent order parameter, whereas
      the long-range interactions are expected to differ with solute. Short-range size
      and shape mechanisms account for solute orientational order measured in magic
      mixtures (e.g., 55 wt % ZLI-1132/N-p-ethoxybenzylidene-p(')-n-butylaniline),
      whereas additional mechanisms are required in other nematic liquid-crystal
      solvents. The results obtained for long-range interactions cannot be rationalized
      in detail using simple mean-field models that incorporate solute dipoles,
      quadrupoles, or polarizabilities. The results suggest that details of the solute
      electrostatics may need to be incorporated into the description of the
      anisotropic intermolecular potential.

PMID- 19388759
TI  - Orientational order of near D(3h) solutes in nematic liquid crystals. II.
      Description via Gay-Berne model with embedded quadrupoles.
AB  - We perform Monte Carlo simulations of a mixture of soft ellipsoids with embedded
      quadrupoles as a model of various chloro- and methyl-substituted benzenes
      dissolved in nematic liquid crystals. We find that oblate Gay-Berne ellipsoids
      with multiple embedded quadrupoles qualitatively reproduce the trend in the order
      parameter asymmetry experimentally observed in NMR spectra. The trend is opposite
      to what is expected on the basis of the interaction of the solute's quadrupole
      with the solvent's average electric field gradient "felt" by dissolved dihydrogen
      molecules. We identify the specific minimum of the solute-solvent interaction
      energy landscape that may produce the unexpected sign of the order parameter
      asymmetry that is seen in the experiment and the simulation.

PMID- 19388760
TI  - Prevalence of approximate square root(t) relaxation for the dielectric alpha
      process in viscous organic liquids.
AB  - This paper presents dielectric relaxation data for organic glass-forming liquids
      compiled from different groups and supplemented by new measurements. The main
      quantity of interest is the "minimum slope" of the alpha dielectric loss plotted
      as a function of frequency in a log-log plot, i.e., the numerically largest slope
      above the loss peak frequency. The data consisting of 347 spectra for 53 liquids
      show prevalence of minimum slopes close to -1/2, corresponding to approximate
      square root(t) dependence of the dielectric relaxation function at short times.
      The paper studies possible correlations between minimum slopes and (1)
      temperature (quantified via the loss peak frequency); (2) how well an inverse
      power-law fits data above the loss peak; (3) degree of time-temperature
      superposition; (4) loss peak half width; (5) deviation from non-Arrhenius
      behavior; (6) loss strength. For the first three points we find correlations that
      show a special status of liquids with minimum slopes close to -1/2. For the last
      three points only fairly insignificant correlations are found, with the exception
      of large-loss liquids that have minimum slopes that are numerically significantly
      larger than 1/2. We conclude that--excluding large-loss liquids--approximate
      square root(t) relaxation appears to be a generic property of the alpha
      relaxation of organic glass formers.

PMID- 19388761
TI  - Spectroscopic study of cis-to-trans tunneling reaction of HCOOD in rare gas
      matrices.
AB  - The higher energy conformer (cis) of HCOOD is prepared by vibrational excitation
      of the trans form. The cis conformer decays back to the conformational ground
      state (trans) via tunneling of deuterium. The tunneling process in HCOOD in rare
      gas matrices is extremely slow (in scale of weeks). We present new measurements
      of the tunneling rate constants, which characterize the efficiency of the cis-to
      trans conversion process in Ne, Ar, Kr, and Xe matrices. The tunneling rates of
      HCOOD follow the trend k(Xe) approximately = k(Kr)>k(Ar) approximately = k(Ne),
      which is anomalous with respect to the reaction barrier of the solvated molecule.
      We propose a semiempirical energetic scheme of solid state solvation, which is
      consistent with all experimental observation. The temperature dependence of the
      tunneling constants rates of HCOOD is very weak compared to HCOOH in all
      matrices. The fundamental vibrational frequencies of the cis and trans conformers
      of HCOOD in various matrices are reported.

PMID- 19388762
TI  - Orientational ordering in solid C60 fullerene-cubane.
AB  - We study the structure and phase behavior of fullerene-cubane C(60) x C(8)H(8) by
      Monte Carlo simulation. Using a simple potential model capturing the icosahedral
      and cubic symmetries of its molecular constituents, we reproduce the
      experimentally observed phase transition from a cubic to an orthorhombic crystal
      lattice and the accompanying rotational freezing of the C(60) molecules. We
      elaborate a scheme to identify the low-temperature orientations of individual
      molecules and to detect a pattern of orientational ordering similar to the
      arrangement of C(60) molecules in solid C(60). Our configuration of orientations
      supports a doubled periodicity along one of the crystal axes.

PMID- 19388763
TI  - Effect of concentration on the thermodynamics of sodium chloride aqueous
      solutions in the supercooled regime.
AB  - Molecular dynamics simulations are performed on two sodium chloride solutions in
      TIP4P water with concentrations c=1.36 mol/kg and c=2.10 mol/kg upon
      supercooling. The isotherms and isochores planes are calculated. The temperature
      of maximum density line and the limit of mechanical stability line are obtained
      from the analysis of the thermodynamic planes. The comparison of the results
      shows that for densities well above the limit of mechanical stability, the
      isotherms and isochores of the sodium chloride aqueous solution shift to lower
      pressures upon increasing concentration while the limit of mechanical stability
      is very similar to that of bulk water for both concentrations. We also find that
      the temperature of maximum density line shifts to lower pressures and
      temperatures upon increasing concentration. Indications of the presence of a
      liquid-liquid coexistence are found for both concentrations.

PMID- 19388764
TI  - Modeling outer-sphere disorder in the symmetry breaking of PPV.
AB  - Disorder plays an important role in the photophysics of conjugated polymers such
      as poly(para-phenylene vinylene) (PPV). The dipole moments measured by
      electroabsorption spectroscopy for a centrosymmetric system such as PPV provide a
      direct quantitative measure of disorder-induced symmetry breaking. Although inner
      sphere (structural) disorder is present, outer-sphere (environmental) disorder
      dominates the symmetry breaking in PPV. This paper develops and compares six
      models of outer-sphere disorder that differ in their representation of the
      electrostatic environment of PPV in glassy solvents. The most detailed model is
      an all-atom description of the solvent glass and this model forms the basis for
      comparison of the less detailed models. Four models are constructed in which
      multipoles are placed at points on a lattice. These lattice models differ in the
      degree to which they include correlation between the lattice spacings and the
      orientations of the multipoles. A simple model that assigns random Gaussian
      distributed electrostatic potentials to each atom in the PPV molecule is also
      considered. Comparison of electronic structure calculations of PPV in these
      electrostatic environments using the all-atom model as a benchmark reveals that
      dipole and quadrupole lattices provide reasonable models of organic glassy
      solvents. Including orientational correlation among the solvent molecules
      decreases the effects of outer-sphere disorder, whereas including correlation in
      the lattice spacings increases the effects. Both the dipole and quadrupole
      moments of the solvent molecules can have significant effects on the symmetry
      breaking and these effects are additive. This additivity provides a convenient
      means for predicting the effects of various glassy solvents based on their
      multipole moments. The results presented here suggest that electrostatic disorder
      can account for the observed symmetry breaking in organic glasses. Furthermore,
      the lattice models are in general agreement with the dipole and quadrupole
      lattice models used to explain the Poole-Frenkel behavior in charge transport
      through disordered organic materials.

PMID- 19388765
TI  - Nanoporous silica-water interfaces studied by sum-frequency vibrational
      spectroscopy.
AB  - Using sum-frequency vibrational spectroscopy, we found that water structure at
      nanoporous silica/water interfaces depended on the nanoporous film structure. For
      a periodic, self-assembled nanoporous film with monosized 2 nm pores occupying
      20% of the top surface area, the surface vibrational spectrum was dominated by
      water in contact with silica, bare or covered by silane, at the top surface. It
      resembled the spectral characteristic of the hydrophilic water/silica or the
      hydrophobic water/silane interface. For a fractal nanoporous film with pores
      ranging from 5 to 50 nm in size occupying 90% of the top surface, the spectrum
      for a trimethyl silane-coated superhydrophobic porous film resembled largely that
      of a water/air interface. Only when the silane was completely removed would the
      spectrum revert to that characteristic of a hydrophilic water/silica interface.
      The surface charging behaviors of the bare nanoporous films in water with
      different pH were monitored by spectroscopic measurements and atomic force
      microscopy force measurements. The point of zero charge for the periodic porous
      film is around pH 2, similar to that of the flat silica surface. The point of
      zero charge could only be determined to be pH<6 for the fractal porous film
      because the thin fractal solid network limited the amount of surface charge and
      therefore, the accuracy of the measurements.

PMID- 19388766
TI  - Simple models for two-dimensional tunable colloidal crystals in rotating ac
      electric fields.
AB  - We compare the behavior of a new two-dimensional aqueous colloidal model system
      with a simple numerical treatment. To the first order the attractive interaction
      between the colloids induced by an in-plane rotating ac electric field is
      dipolar, while the charge stabilization leads to a shorter ranged, Yukawa-like
      repulsion. In the crystal-like "rafts" formed at sufficient field strengths, we
      find quantitative agreement between experiment and Monte Carlo simulation, except
      in the case of strongly interacting systems, where the well depth of the
      effective potential exceeds 250 times the thermal energy. The "lattice constant"
      of the crystal-like raft is located approximately at the minimum of the effective
      potential, resulting from the sum of the Yukawa and dipolar interactions. The
      experimental system has display applications, owing to the possibility of tuning
      the lattice spacing with the external electric field. Limitations in the applied
      field strength and relative range of the electrostatic interactions of the
      particles result in a reduction in tunable lattice spacing for small and large
      particles, respectively. The optimal particle size for maximizing the lattice
      spacing tunability was found to be around 1000 nm.

PMID- 19388767
TI  - Nucleation in A/B/AB blends: interplay between microphase assembly and macrophase
      separation.
AB  - We study the interplay between microphase assembly and macrophase separation in
      A/B/AB ternary polymer blends by examining the free energy of localized
      fluctuation structures (micelles or droplets), with emphasis on the thermodynamic
      relationship between swollen micelles (microemulsion) and the macrophase
      separated state, using self-consistent field theory and an extended capillary
      model. Upon introducing homopolymer B into a micelle-forming binary polymer blend
      A/AB, micelles can be swollen by B. A small amount of component B (below the A
      rich binodal of macrophase coexistence) will not affect the stability of the
      swollen micelles. A large excess of homopolymer, B, will induce a microemulsion
      failure and lead to a macrophase separation. Between the binodal and the
      microemulsion failure concentration, macrophase separation in A/B/AB occurs by a
      two-step nucleation mechanism via a metastable microemulsion droplet of finite
      size. Our results illustrate a recently proposed argument that the two-step
      nucleation via a metastable intermediate is a general phenomenon in systems
      involving short-range attraction and long-range repulsion.

PMID- 19388768
TI  - Structure and phase diagram of an adhesive colloidal dispersion under high
      pressure: a small angle neutron scattering, diffusing wave spectroscopy, and
      light scattering study.
AB  - We have applied small angle neutron scattering (SANS), diffusing wave
      spectroscopy (DWS), and dynamic light scattering (DLS) to investigate the phase
      diagram of a sterically stabilized colloidal system consisting of octadecyl
      grafted silica particles dispersed in toluene. This system is known to exhibit
      gas-liquid phase separation and percolation, depending on temperature T, pressure
      P, and concentration phi. We have determined by DLS the pressure dependence of
      the coexistence temperature and the spinodal temperature to be dP/dT=77 bar/K.
      The gel line or percolation limit was measured by DWS under high pressure using
      the condition that the system became nonergodic when crossing it and we
      determined the coexistence line at higher volume fractions from the DWS limit of
      turbid samples. From SANS measurements we determined the stickiness parameter
      tau(B)(P,T,phi) of the Baxter model, characterizing a polydisperse adhesive hard
      sphere, using a global fit routine on all curves in the homogenous regime at
      various temperatures, pressures, and concentrations. The phase coexistence and
      percolation line as predicted from tau(B)(P,T,phi) correspond with the
      determinations by DWS and were used to construct an experimental phase diagram
      for a polydisperse sticky hard sphere model system. A comparison with theory
      shows good agreement especially concerning the predictions for the percolation
      threshold. From the analysis of the forward scattering we find a critical scaling
      law for the susceptibility corresponding to mean field behavior. This finding is
      also supported by the critical scaling properties of the collective diffusion.

PMID- 19388769
TI  - Dendrimers as synthetic gene vectors: cell membrane attachment.
AB  - We present molecular-level simulations of dendrimer/DNA complexes in the presence
      of a model cell membrane. We determine the required conditions for the complex to
      arrive intact at the membrane, and the lifetime of the complex as it resides
      attached to the membrane. Our simulations directly pertain to critical issues
      arising in emerging gene delivery therapeutic applications, where a molecular
      carrier is required to deliver DNA segments to the interior of living cells.

PMID- 19388772
TI  - A cadaverically evaluated dynamic FEM model of closed-chain TKR mechanics.
AB  - Knowledge of the behavior and mechanics of a total knee replacement (TKR) in an
      in vivo environment is key to optimizing the functional outcomes of the implant
      procedure. Computational modeling has shown to be an important tool for
      investigating biomechanical variables that are difficult to address
      experimentally. To assist in examining TKR mechanics, a dynamic finite-element
      model of a TKR is presented. The objective of the study was to develop and
      evaluate a model that could simulate full knee motion using a physiologically
      consistent quadriceps action, without prescribed joint kinematics. The model
      included tibiofemoral (TFJs) and patellofemoral joints (PFJs), six major ligament
      bundles and was driven by a uni-axial representation of a quadricep muscle. An
      initial parameter screening analysis was performed to assess the relative
      importance of 31 different model parameters. This analysis showed that ligament
      insertion location and initial ligament strain were significant factors affecting
      simulated joint kinematics and loading, with the contact friction coefficient
      playing a lesser role and ligament stiffness having little effect. The model was
      then used to simulate in vitro experiments utilizing a flexed-knee-stance testing
      rig. General model performance was assessed by comparing simulation results with
      experimentally measured kinematics and tibial reaction forces collected from two
      implanted specimens. The simulations were able to reproduce experimental
      differences observed between the test specimens and were able to accurately
      predict trends seen in the tibial reaction loads. The simulated kinematics of the
      TFJ and PFJ were less consistent when compared with experimental data but still
      reproduced many trends.

PMID- 19388771
TI  - Dynamic tensile failure mechanics of the musculoskeletal neck using a cadaver
      model.
AB  - Although the catapult phase of pilot ejections has been well characterized in
      terms of human response to compressive forces, the effect of the forces on the
      human body during the ensuing ejection phases (including windblast and parachute
      opening shock) has not been thoroughly investigated. Both windblast and parachute
      opening shock have been shown to induce dynamic tensile forces in the human
      cervical spine. However, the human tolerance to such loading is not well known.
      Therefore, the main objective of this research project was to measure human
      tensile neck failure mechanics to provide data for computational modeling,
      anthropometric test device development, and improved tensile injury criteria.
      Twelve human cadaver specimens, including four females and eight males with a
      mean age of 50.1+/-9 years, were subjected to dynamic tensile loading through the
      musculoskeletal neck until failure occurred. Failure load, failure strain, and
      tensile stiffness were measured and correlated with injury type and location. The
      mean failure load for the 12 specimens was 3100+/-645 N, mean failure strain was
      16.7+/-5.4%, and mean tensile stiffness was 172+/-54.5 N/mm. The majority of
      injuries (8) occurred in the upper cervical spine (Oc-C3), and none took place in
      the midcervical region (C3-C5). The results of this study assist in filling the
      existing void in dynamic tensile injury data and will aid in developing improved
      neck injury prevention strategies.

PMID- 19388773
TI  - Design optimization of a total hip prosthesis for wear reduction.
AB  - Aseptic loosening from polyethylene debris is the leading cause of failure for
      metal-on-polyethylene hip implants. The accumulation of wear debris can lead to
      osteolysis, the degradation of bone surrounding the implant components. In the
      present study, a parametric three-dimensional finite element model of an
      uncemented total hip replacement prosthesis was constructed and implanted into a
      femur model constructed from computed tomography (CT) scan data. Design
      optimization was performed considering volumetric wear as an objective function
      using a computational model validated in a previous study through in vitro wear
      assessment. Constraints were used to maintain the physiological range of motion
      of wear-optimum designs. Loading conditions for both walking and stair climbing
      were considered in the analysis. In addition, modification of the acetabular
      liner surface nodes was performed in discrete intervals to reflect the actual
      wear and creep damage occurring on the liner surface. Stair climbing was found to
      produce 49% higher volumetric wear than walking. Using a sensitivity analysis, it
      was found that the objective function sensitivity to the chosen design variables
      was identical for both walking and stair climbing. The greatest reduction in
      volumetric wear achieved while maintaining a physiological range of motion was
      16%. It was found that including nodal modification in the sensitivity analysis
      produced little or no difference in the sensitivity analysis results due to the
      linear nature of volumetric wear progression. Thus, nodal modification was not
      used in optimization. An increase in the maximum contact pressure was observed
      for all wear-optimized designs, and an increase in head-liner penetration was
      found to be related to a reduction in volumetric wear.

PMID- 19388774
TI  - Deformation-dependent enzyme mechanokinetic cleavage of type I collagen.
AB  - Collagen is a key structural protein in the extracellular matrix of many tissues.
      It provides biological tissues with tensile mechanical strength and is
      enzymatically cleaved by a class of matrix metalloproteinases known as
      collagenases. Collagen enzymatic kinetics has been well characterized in
      solubilized, gel, and reconstituted forms. However, limited information exists on
      enzyme degradation of structurally intact collagen fibers and, more importantly,
      on the effect of mechanical deformation on collagen cleavage. We studied the
      degradation of native rat tail tendon fibers by collagenase after the fibers were
      mechanically elongated to strains of epsilon=1-10%. After the fibers were
      elongated and the stress was allowed to relax, the fiber was immersed in
      Clostridium histolyticum collagenase and the decrease in stress (sigma) was
      monitored as a means of calculating the rate of enzyme cleavage of the fiber. An
      enzyme mechanokinetic (EMK) relaxation function T(E)(epsilon) in s(-1) was
      calculated from the linear stress-time response during fiber cleavage, where
      T(E)(epsilon) corresponds to the zero order Michaelis-Menten enzyme-substrate
      kinetic response. The EMK relaxation function T(E)(epsilon) was found to decrease
      with applied strain at a rate of approximately 9% per percent strain, with
      complete inhibition of collagen cleavage predicted to occur at a strain of
      approximately 11%. However, comparison of the EMK response (T(E) versus epsilon)
      to collagen's stress-strain response (sigma versus epsilon) suggested the
      possibility of three different EMK responses: (1) constant T(E)(epsilon) within
      the toe region (epsilon<3%), (2) a rapid decrease ( approximately 50%) in the
      transition of the toe-to-heel region (epsilon congruent with3%) followed by (3) a
      constant value throughout the heel (epsilon=3-5%) and linear (epsilon=5-10%)
      regions. This observation suggests that the mechanism for the strain-dependent
      inhibition of enzyme cleavage of the collagen triple helix may be by a
      conformational change in the triple helix since the decrease in T(E)(epsilon)
      appeared concomitant with stretching of the collagen molecule.

PMID- 19388775
TI  - Magnitude and duration of stretch modulate fibroblast remodeling.
AB  - Mechanical cues modulate fibroblast tractional forces and remodeling of
      extracellular matrix in healthy tissue, healing wounds, and engineered matrices.
      The goal of the present study is to establish dose-response relationships between
      stretch parameters (magnitude and duration per day) and matrix remodeling metrics
      (compaction, strength, extensibility, collagen content, contraction, and
      cellularity). Cyclic equibiaxial stretch of 2-16% was applied to fibroblast
      populated fibrin gels for either 6 h or 24 h/day for 8 days. Trends in matrix
      remodeling metrics as a function of stretch magnitude and duration were analyzed
      using regression analysis. The compaction and ultimate tensile strength of the
      tissues increased in a dose-dependent manner with increasing stretch magnitude,
      yet remained unaffected by the duration in which they were cycled (6 h/day versus
      24 h/day). Collagen density increased exponentially as a function of both the
      magnitude and duration of stretch, with samples stretched for the reduced
      duration per day having the highest levels of collagen accumulation. Cell number
      and failure tension were also dependent on both the magnitude and duration of
      stretch, although stretch-induced increases in these metrics were only present in
      the samples loaded for 6 h/day. Our results indicate that both the magnitude and
      the duration per day of stretch are critical parameters in modulating fibroblast
      remodeling of the extracellular matrix, and that these two factors regulate
      different aspects of this remodeling. These findings move us one step closer to
      fully characterizing culture conditions for tissue equivalents, developing
      improved wound healing treatments and understanding tissue responses to changes
      in mechanical environments during growth, repair, and disease states.

PMID- 19388776
TI  - A theoretical study of mechanical stability of arteries.
AB  - This study proposes a mathematical model for studying stability of arteries
      subjected to a longitudinal extension and a periodic pressure. An artery was
      considered as a straight composite beam comprised of an external thick-walled
      tube and a fluid core. The dynamic criterion for stability was used, based on
      analyzing the small transverse vibrations superposed on the finite deformation of
      the vessel under static load. In contrast to the case of a static pressurization,
      in which buckling is only possible if the load produces a critical axial
      compressive force, a loss of stability of arteries under periodic pressure occurs
      under many combinations of load parameters. Instability occurs as a parametric
      resonance characterized by an exponential increase in the amplitude of transverse
      vibrations over several bands of pressure frequencies. The effects of load
      parameters were analyzed on the basis of the results for a dynamic and static
      stability of a rabbit thoracic aorta. Under normal physiological loads the artery
      is in a stable configuration. Static instability occurs under high distending
      pressures and low longitudinal stretch ratios. When the artery is subjected to
      periodic pressure, an independent increase in the mean pressure, amplitude of the
      periodic pressure, or frequency, most often, but not always, increases the risk
      of stability loss. In contrary, an increase in longitudinal stretch ratio most
      likely, but not certain, stabilizes the vessel. It was shown that adaptive
      geometrical remodeling due to an increase in mean pressure and flow does not
      affect artery stability.

PMID- 19388777
TI  - Accounting for inclusions and voids allows the prediction of tensile fatigue life
      of bone cement.
AB  - Previous attempts by researchers to predict the fatigue behavior of bone cement
      have been capable of predicting the location of final failure in complex
      geometries but incapable of predicting cement fatigue life to the right order of
      magnitude of loading cycles. This has been attributed to a failure to model the
      internal defects present in bone cement and their associated stress
      singularities. In this study, dog-bone-shaped specimens of bone cement were micro
      computed-tomography (microCT) scanned to generate computational finite element
      (FE) models before uniaxial tensile fatigue testing. Acoustic emission (AE)
      monitoring was used to locate damage events in real time during tensile fatigue
      tests and to facilitate a comparison with the damage predicted in FE simulations
      of the same tests. By tracking both acoustic emissions and predicted damage back
      to microCT scans, barium sulfate (BaSO(4)) agglomerates were found not to be
      significant in determining fatigue life (p=0.0604) of specimens. Both the
      experimental and numerical studies showed that diffuse damage occurred throughout
      the gauge length. A good linear correlation (R(2)=0.70, p=0.0252) was found
      between the experimental and the predicted tensile fatigue life. Although the FE
      models were not always able to predict the correct failure location, damage was
      predicted in simulations at areas identified as experiencing damage using AE
      monitoring.

PMID- 19388778
TI  - Motion estimation using point cluster method and Kalman filter.
AB  - The most frequently used method in a three dimensional human gait analysis
      involves placing markers on the skin of the analyzed segment. This introduces a
      significant artifact, which strongly influences the bone position and orientation
      and joint kinematic estimates. In this study, we tested and evaluated the effect
      of adding a Kalman filter procedure to the previously reported point cluster
      technique (PCT) in the estimation of a rigid body motion. We demonstrated the
      procedures by motion analysis of a compound planar pendulum from indirect opto
      electronic measurements of markers attached to an elastic appendage that is
      restrained to slide along the rigid body long axis. The elastic frequency is
      close to the pendulum frequency, as in the biomechanical problem, where the soft
      tissue frequency content is similar to the actual movement of the bones.
      Comparison of the real pendulum angle to that obtained by several estimation
      procedures--PCT, Kalman filter followed by PCT, and low pass filter followed by
      PCT--enables evaluation of the accuracy of the procedures. When comparing the
      maximal amplitude, no effect was noted by adding the Kalman filter; however, a
      closer look at the signal revealed that the estimated angle based only on the PCT
      method was very noisy with fluctuation, while the estimated angle based on the
      Kalman filter followed by the PCT was a smooth signal. It was also noted that the
      instantaneous frequencies obtained from the estimated angle based on the PCT
      method is more dispersed than those obtained from the estimated angle based on
      Kalman filter followed by the PCT method. Addition of a Kalman filter to the PCT
      method in the estimation procedure of rigid body motion results in a smoother
      signal that better represents the real motion, with less signal distortion than
      when using a digital low pass filter. Furthermore, it can be concluded that
      adding a Kalman filter to the PCT procedure substantially reduces the dispersion
      of the maximal and minimal instantaneous frequencies.

PMID- 19388779
TI  - The use of external transducers for estimating bone strain at the distal tibia
      during impact activity.
AB  - Noninvasive methods for monitoring the in vivo loading environment of human bone
      are needed to determine osteogenic loading patterns that reduce the potential for
      bone injury. The purpose of this study was to determine whether the vertical
      ground reaction impact force (impact force) and leg acceleration could be used to
      estimate internal bone strain at the distal tibia during impact activity. Impact
      loading was delivered to the heels of human-cadaveric lower extremities. The
      effects of impact mass and contact velocity on peak bone strain, impact force,
      leg acceleration, and computed impact force (leg acceleration *impact mass) were
      investigated. Regression analysis was used to predict bone strain from six
      different models. Apart from leg acceleration, all variables responded to impact
      loading similarly. Increasing impact mass resulted in increased bone strain,
      impact force, and computed impact force, but decreased leg acceleration. The best
      models for bone strain prediction included impact force and tibial cross
      sectional area (R(2)=0.94), computed impact force and tibial cross-sectional area
      (R(2)=0.84), and leg acceleration and tibial cross-sectional area (R(2)=0.73).
      Results demonstrate that when attempting to estimate bone strain from external
      transducers some measure of bone strength must be considered. Although it is not
      recommended that the prediction equations developed in this study be used to
      predict bone strain in vivo, the strong relationship between bone strain, impact
      force, and computed impact force suggested that force platforms and leg
      accelerometers can be used for a surrogate measure of bone strain.

PMID- 19388780
TI  - Hemodynamics of the mitral valve under edge-to-edge repair: an in vitro steady
      flow study.
AB  - Edge-to-edge repair (ETER) is a mitral valve repair technique that restores
      valvular competence by suturing together the free edges of two leaflets. This
      repair technique alters mitral valve inflow and thus left ventricle hemodynamics
      during diastole. Our objective was to investigate fluid mechanics immediately
      downstream of the mitral valve under ETER during diastole. Fresh porcine mitral
      valves of the annulus size M32 with chordae removed were installed into a steady
      flow loop simulating a peak diastolic inflow through the mitral valve. Digital
      particle image velocimetry was used to measure the velocity field immediately
      downstream of the mitral valve under normal and ETER conditions. First, to study
      the suture length effect, suture was applied in the central position of the
      leaflet edge with suture lengths of 3 mm, 6 mm, and 9 mm, respectively. Then, 3
      mm suture was set in the central, lateral, and commissural positions of the
      leaflet edge to study the suture position effect. Flow rate was 15 l/min.
      Velocity, Reynolds shear stress (RSS), and effective orifice area were assessed.
      A total of five mitral valves were tested. The normal mitral valve without the
      ETER had one jet downstream of the valve, but the mitral valve with the central
      or lateral sutures under the ETER had two jets downstream of the valve with a
      recirculation region downstream of the suture. The maximum velocity, the maximum
      RSS in the jets, the pressure drop across the mitral valve, and the jet
      deflection angle increased with the increase in suture length in the central
      position. When the suture position effect was investigated with the 3 mm suture,
      the maximum velocity, the maximum RSS, and the pressure drop across the valve in
      the central suture position were greater than those of the lateral and the
      commissural suture positions. The lateral suture demonstrated major and minor
      jets with the greater maximum velocity and maximum RSS in the major jet. When the
      suture was in the commissural position, the flow field downstream of the mitral
      valve was similar to that of the normal mitral valve without the ETER. The
      effective orifice area was smallest when the suture was applied in the central
      position as compared with other suture positions. Both suture length and position
      have an important impact on fluid mechanics downstream of the mitral valve under
      the ETER in terms of flow pattern, maximum velocity, and RSS distribution. The
      altered hemodynamics of the mitral valve and thus of the left ventricle by the
      ETER may change mitral valve and left ventricle function.

PMID- 19388781
TI  - Peripapillary and posterior scleral mechanics--part I: development of an
      anisotropic hyperelastic constitutive model.
AB  - The sclera is the white outer shell and principal load-bearing tissue of the eye
      as it sustains the intraocular pressure. We have hypothesized that the mechanical
      properties of the posterior sclera play a significant role in and are altered by
      the development of glaucoma-an ocular disease manifested by structural damage to
      the optic nerve head. An anisotropic hyperelastic constitutive model is presented
      to simulate the mechanical behavior of the posterior sclera under acute
      elevations of intraocular pressure. The constitutive model is derived from fiber
      reinforced composite theory, and incorporates stretch-induced stiffening of the
      reinforcing collagen fibers. Collagen fiber alignment was assumed to be
      multidirectional at local material points, confined within the plane tangent to
      the scleral surface, and described by the semicircular von Mises distribution.
      The introduction of a model parameter, namely, the fiber concentration factor,
      was used to control collagen fiber alignment along a preferred fiber orientation.
      To investigate the effects of scleral collagen fiber alignment on the overall
      behaviors of the posterior sclera and optic nerve head, finite element
      simulations of an idealized eye were performed. The four output quantities
      analyzed were the scleral canal expansion, the scleral canal twist, the posterior
      scleral canal deformation, and the posterior laminar deformation. A
      circumferential fiber organization in the sclera restrained scleral canal
      expansion but created posterior laminar deformation, whereas the opposite was
      observed with a meridional fiber organization. Additionally, the fiber
      concentration factor acted as an amplifying parameter on the considered outputs.
      The present model simulation suggests that the posterior sclera has a large
      impact on the overall behavior of the optic nerve head. It is therefore
      primordial to provide accurate mechanical properties for this tissue. In a
      companion paper (Girard, Downs, Bottlang, Burgoyne, and Suh, 2009, "Peripapillary
      and Posterior Scleral Mechanics--Part II: Experimental and Inverse Finite Element
      Characterization," ASME J. Biomech. Eng., 131, p. 051012), we present a method to
      measure the 3D deformations of monkey posterior sclera and extract mechanical
      properties based on the proposed constitutive model with an inverse finite
      element method.

PMID- 19388782
TI  - Peripapillary and posterior scleral mechanics--part II: experimental and inverse
      finite element characterization.
AB  - The posterior sclera likely plays an important role in the development of
      glaucoma, and accurate characterization of its mechanical properties is needed to
      understand its impact on the more delicate optic nerve head--the primary site of
      damage in the disease. The posterior scleral shells from both eyes of one rhesus
      monkey were individually mounted on a custom-built pressurization apparatus.
      Intraocular pressure was incrementally increased from 5 mm Hg to 45 mm Hg, and
      the 3D displacements were measured using electronic speckle pattern
      interferometry. Finite element meshes of each posterior scleral shell were
      reconstructed from data generated by a 3D digitizer arm (shape) and a 20 MHz
      ultrasound transducer (thickness). An anisotropic hyperelastic constitutive model
      described in a companion paper (Girard, Downs, Burgoyne, and Suh, 2009,
      "Peripapillary and Posterior Scleral Mechanics--Part I: Development of an
      Anisotropic Hyperelastic Constitutive Model," ASME J. Biomech. Eng., 131, p.
      051011), which includes stretch-induced stiffening and multidirectional alignment
      of the collagen fibers, was applied to each reconstructed mesh. Surface node
      displacements of each model were fitted to the experimental displacements using
      an inverse finite element method, which estimated a unique set of 13 model
      parameters. The predictions of the proposed constitutive model matched the 3D
      experimental displacements well. In both eyes, the tangent modulus increased
      dramatically with IOP, which indicates that the sclera is mechanically nonlinear.
      The sclera adjacent to the optic nerve head, known as the peripapillary sclera,
      was thickest and exhibited the lowest tangent modulus, which might have
      contributed to the uniform distribution of the structural stiffness for each
      entire scleral shell. Posterior scleral deformation following acute IOP
      elevations appears to be nonlinear and governed by the underlying scleral
      collagen microstructure as predicted by finite element modeling. The method is
      currently being used to characterize posterior scleral mechanics in normal (young
      and old), early, and moderately glaucomatous monkey eyes.

PMID- 19388783
TI  - Stress changes in intervertebral discs of the cervical spine due to partial
      discectomies and fusion.
AB  - Spine discectomy and fusion is a widely used surgical procedure to correct
      irreversible degenerative diseases and injuries to the intervertebral disk. The
      surgical procedure involves the removal of the damage disk material, the
      decortication of the fusion site, and the placement of the bone graft. Fusion is
      believed to generate additional stresses in the neighboring disks, which can
      subsequently lead to new disk degeneration and re-operation. The autologous bone
      has proven to be the best material for the fusion. However, the autologous bone
      has three major disadvantages: the high rate of donor site morbidity, the limited
      and sometimes poor quality of the amounts of bone available, and the extra
      operative time needed for harvest. For these reasons this study is undertaken to
      estimate the optimum amount of bone graft needed for a discectomy and correlate
      it to the change in stress in adjacent levels. A detailed and validated 3D finite
      element model of the complete human cervical spine (C1-T1) was altered to
      simulate segmental full and partial discectomies. One full fusion (bone graft
      occupies about 90% of the vertebral body) and seven partial fusions (bone graft
      occupies about 10%, 20%, 30%, 40%, 50%, 65%, and 75% of the vertebral body) were
      simulated at each of the four mid- and lower single levels of the cervical spine
      and the relationship between the change in stresses in the adjacent levels and
      the bone graft size (area) was studied. The changes in stress were compared with
      the previously obtained results of the unfused models. The fused and unfused
      models were preloaded with a 73.6 N compressive force representing the weight of
      the head and with a 1.5 Nm physiological moment in flexion, extension, lateral
      bending, and axial rotation. More than 132 cases were analyzed. The results
      showed that the necessary amount of bone graft needed for discectomy depends on
      the cervical disk level to be fused and varies between 30% and 75% of the disk
      area. The results also suggested that there is a threshold size of the bone graft
      area, before and/or after which, the long-term effects of the change in stresses
      in adjacent disks are biomechanically consequential.

PMID- 19388784
TI  - Thin film nitinol microstent for aneurysm occlusion.
AB  - Thin film nitinol produced by sputter deposition was used in the design of
      microstents intended to treat small vessel aneurysms. Thin film microstents were
      fabricated by "hot-target" dc sputter deposition. Both stress-strain curves and
      differential scanning calorimetry curves were generated for the film used to
      fabricate stents. The films used for stents had an A(f) temperature of
      approximately 36 degrees C allowing for body activated response from a
      microcatheter. The 10 microm film was only slightly radio-opaque; thus, a Td
      marker was attached to the stents to guide fluoroscopic delivery. Thin film
      microstents were tested in a flow loop with and without nitinol support skeletons
      to give additional radial support. Stents could be compressed into and easily
      delivered with <3 Fr catheters. Theoretical frictional and wall drag forces on a
      thin film nitinol small vessel vascular stent were calculated, and the radial
      force exerted by thin film stents was evaluated theoretically and experimentally.
      In vivo studies in swine confirmed that thin film nitinol microstents could be
      deployed accurately and consistently in the swine cranial vasculature.

PMID- 19388785
TI  - Effect of geometrical uncertainty on cemented hip implant structural integrity.
AB  - A large number of parameters such as material properties, geometry, and
      structural strength are involved in the design and analysis of cemented hip
      implants. Uncertainties in these parameters have a potential to compromise the
      structural performance and lifetime of implants. Statistical analyses are well
      suited to investigating this type of problem as they can estimate the influence
      of these uncertainties on the incidence of failure. Recent investigations have
      focused on the effect of uncertainty in cement properties and loading condition
      on the integrity of the construct. The present study hypothesizes that
      geometrical uncertainties will play a role in cement mantle failure. Finite
      element input parameters were simulated as random variables and different modes
      of failure were investigated using a response surface method (RSM). The magnitude
      of random von Mises stresses varied up to 8 MPa, compared with a maximum nominal
      value of 2.38 MPa. Results obtained using RSM are shown to match well with a
      benchmark direct Monte Carlo simulation method. The resulting probability that
      the maximum cement stress will exceed the nominal stress is 62%. The load and the
      bone and prosthesis geometries were found to be the parameters most likely to
      influence the magnitude of the cement stresses and therefore to contribute most
      to the probability of failure.

PMID- 19388786
TI  - Determination of low-pass filter cutoff frequencies for high-rate biomechanical
      signals obtained using videographic analysis.
AB  - Diffuse brain injury (DBI) commonly results from blunt impact followed by sudden
      head rotation, wherein severity is a function of rotational kinematics. A
      noninvasive in vivo rat model was designed to further investigate this
      relationship. Due to brain mass differences between rats and humans, rotational
      acceleration magnitude indicative of rat DBI ( approximately 350 krad/s(2)) has
      been estimated as approximately 60 times greater than that of human DBI (
      approximately 6 krad/s(2)). Prior experimental testing attempted to use standard
      transducers such as linear accelerometers to measure loading kinematics. However,
      such measurement techniques were intrusive to experimental model operation.
      Therefore, initial studies using this experimental model obtained rotational
      displacement data from videographic images and implemented a finite difference
      differentiation (FDD) method to obtain rotational velocity and acceleration.
      Unfortunately, this method amplified high-frequency, low-amplitude noise, which
      interfered with signal magnitude representation. Therefore, a coherent average
      technique was implemented to improve the measurement of rotational kinematics
      from videographic images, and its results were compared with those of the
      previous FDD method. Results demonstrated that the coherent method accurately
      determined a low-pass filter cutoff frequency specific to pulse characteristics.
      Furthermore, noise interference and signal attenuation were minimized compared
      with the FDD technique.

PMID- 19388787
TI  - An understanding of the mechanism that promotes adhesion between roughened
      titanium implants and mineralized tissue.
AB  - A previously developed laser spallation technique to determine the tensile
      strength of thin film interfaces was successfully adopted to study the effect of
      microsurface roughness of titanium disks on the adhesion strength of mineralized
      bone tissue. The study demonstrated that mineralized tissue has about 25% higher
      interfacial strength when it is cultured on the acid-etched titanium surface than
      on its machined counterpart. Specifically, interfacial tensile strength of 179+/
      4.4 MPa and 224+/-2.6 MPa were measured when the mineralized tissue was processed
      on the machined titanium and acid-etched titanium surfaces, respectively. Since
      in the laser spallation experiment, the mineralized tissue is pulled normal to
      the interface, this increase is attributed to the stronger interfacial bonding on
      account of higher surface energy associated with the acid-etched surface. This
      enhanced local chemical bonding further enhances the roughness-related mechanical
      interlocking effect. These two effects at very different length scales--atomic
      (enhanced bonding) versus continuum (roughness-related interlocking)-act
      synergistically and explain the widely observed clinical success of roughened
      dental implants.

PMID- 19388788
TI  - Propulsive efficiency of the underwater dolphin kick in humans.
AB  - Three-dimensional fully unsteady computational fluid dynamic simulations of five
      Olympic-level swimmers performing the underwater dolphin kick are used to
      estimate the swimmer's propulsive efficiencies. These estimates are compared with
      those of a cetacean performing the dolphin kick. The geometries of the swimmers
      and the cetacean are based on laser and CT scans, respectively, and the stroke
      kinematics is based on underwater video footage. The simulations indicate that
      the propulsive efficiency for human swimmers varies over a relatively wide range
      from about 11% to 29%. The efficiency of the cetacean is found to be about 56%,
      which is significantly higher than the human swimmers. The computed efficiency is
      found not to correlate with either the slender body theory or with the Strouhal
      number.

PMID- 19388789
TI  - Effect of mechanical loading on electrical conductivity in human intervertebral
      disk.
AB  - The intervertebral disk (IVD), characterized as a charged, hydrated soft tissue,
      is the largest avascular structure in the body. Mechanical loading to the disk
      results in electromechanical transduction phenomenon as well as altered transport
      properties. Electrical conductivity is a material property of tissue depending on
      ion concentrations and diffusivities, which are in turn functions of tissue
      composition and structure. The aim of this study was to investigate the effect of
      mechanical loading on electrical behavior in human IVD tissues. We hypothesized
      that electrical conductivity in human IVD is strain-dependent, due to change in
      tissue composition caused by compression, and inhomogeneous, due to tissue
      structure and composition. We also hypothesized that conductivity in human
      annulus fibrosus (AF) is anisotropic, due to the layered structure of the tissue.
      Three lumbar IVDs were harvested from three human spines. From each disk, four AF
      specimens were prepared in each of the three principal directions (axial,
      circumferential, and radial), and four axial nucleus pulposus (NP) specimens were
      prepared. Conductivity was determined using a four-wire sense-current method and
      a custom-designed apparatus by measuring the resistance across the sample.
      Resistance measurements were taken at three levels of compression (0%, 10%, and
      20%). Scanning electron microscopy (SEM) images of the human AF tissue were
      obtained in order to correlate tissue structure with conductivity results.
      Increasing compressive strain significantly decreased conductivity for all groups
      (p<0.05, analysis of variance (ANOVA)). Additionally, specimen orientation
      significantly affected electrical conductivity in the AF tissue, with
      conductivity in the radial direction being significantly lower than that in the
      axial or circumferential directions at all levels of compressive strain (p<0.05,
      ANOVA). Finally, conductivity in the NP tissue was significantly higher than that
      in the AF tissue (p<0.05, ANOVA). SEM images of the AF tissues showed evidence of
      microtubes orientated in the axial and circumferential directions, but not in the
      radial direction. This may suggest a relationship between tissue morphology and
      the anisotropic behavior of conductivity in the AF. The results of this
      investigation demonstrate that electrical conductivity in human IVD is strain
      dependent and inhomogeneous, and that conductivity in the human AF tissue is
      anisotropic (i.e., direction-dependent). This anisotropic behavior is correlated
      with tissue structure shown in SEM images. This study provides important
      information regarding the effects of mechanical loading on solute transport and
      electrical behavior in IVD tissues.

PMID- 19388791
TI  - Influence of nanotube preparation in aquatic bioassays.
AB  - Knowledge gaps in nanomaterial fate and toxicity currently limit the ability of
      risk assessments to characterize the environmental implications of nanomaterials.
      This problem is further complicated by the lack of standardized characterization
      and preparation methodologies for researchers to gain the needed information to
      assist risk assessors. In the present study, data were generated to determine if
      multiwalled nanotube (MWNT) fate and toxicity are altered by engineered surface
      modifications or by different dispersal methods. While dissolved organic matter
      was a good dispersing agent of MWNTs in water, the humic acid fraction was a more
      effective dispersant than the fulvic acid fraction. When stabilized in organic
      matter, the functional group attached to the MWNT controlled its toxicity.
      Underivatized MWNTs induced relatively moderate toxicity to Ceriodaphnia dubia
      after 96 h (25 +/- 19% survival at 26 mg/L), while hydrophilic groups (hydroxyl,
      carboxyl) reduced this toxicity (93 +/- 12% survival at 48 mg/L). However, other
      functional groups (alkyl, amine) increased toxicity (0 +/- 0% survival at <15
      mg/L). In dispersal method studies, sonication of MWNTs increased fragmentation
      relative to magnetic stirring. The sonication treatment of MWNTs also slightly
      reduced the mortality of C. dubia in the water column but increased toxicity in
      the sediment to Leptocheirus plumulosus and Hyalella azteca. Findings in the
      present study indicate that nanotubes engineered for specific applications need
      to be managed independently and that laboratory methods to disperse and test
      nanotubes in bioassays need to be standardized to obtain repeatable results for
      comparison of materials.

PMID- 19388790
TI  - Parasite-induced changes in nitric oxide levels in Drosophila paramelanica.
AB  - In larvae of Drosophila paramelanica, eggs and larvae of the endoparasitic wasp
      Leptopilina heterotoma succumb to an effective host reaction that does not
      involve blood cell-mediated melanotic encapsulation, a response that
      characterizes cellular immunity in various species of Drosophila and in many
      insects and other arthropods. A significant increase occurs, however, in the
      number of lamellocytes, a type of blood cell that functions in encapsulation
      reactions. The appearance of activated lamellocytes in D. paramelanica is viewed
      as an early response to infection, one most likely initiated by non-self
      recognition processes that similarly function in other wasp-infected Drosophila.
      However, ensuing cytotoxic responses, about which little is presently known, are
      not accompanied by melanotic encapsulation in D. paramelanica. Concurrent
      analyses of the cell-signaling molecule nitric oxide (*NO) revealed significant
      alterations in the levels of this free radical during the early stages of
      infection, most notably a dramatic increase immediately upon infection, and
      precipitous decreases occurring at times when parasites were killed. Injections
      of a specific inhibitor of nitric oxide synthase (NOS) into the host's body
      cavity prior to infection significantly increased parasite survival. These
      observations suggest some involvement of *NO in the host immune response, either
      in recruiting hemocytes to sites of infection or as a component of the insect's
      cytotoxic arsenal, given the capacity of the radical to generate toxic molecules
      through interactions with various intermediates of oxygen and nitrogen.

PMID- 19388792
TI  - Considerations for research on the environmental fate and effects of
      nanoparticles.

PMID- 19388793
TI  - Influence of nitrogen and phosphorus concentrations and ratios on Lemna gibba
      growth responses to triclosan in laboratory and stream mesocosm experiments.
AB  - The effects of co-occurring nutrient and contaminant stressors are very likely to
      interact in aquatic systems, particularly at the level of primary producers. Site
      specific nitrogen (N) and phosphorus (P) concentrations are often much lower and
      differ in relative availability than those used in nutrient-saturated laboratory
      assays for aquatic plants, which can introduce uncertainty in prospective
      ecological hazard and risk assessments. Because triclosan, an antimicrobial agent
      included in personal care products, potentially presents high relative risk among
      antimicrobial agents to aquatic plants and algae, we performed laboratory
      experiments with the model aquatic macrophyte Lemna gibba across a gradient of
      environmentally relevant N:P levels with and without triclosan co-exposure. Frond
      numbers (7 d) were significantly higher in N:P treatments of 16 and 23 but were
      lower in N:P of 937 and 2,500 treatments relative to standardized control media
      (N:P=3). When triclosan co-exposure occurred at high nutrient concentrations,
      frond number median effective concentration values at N:P 0.75, 3, and 16 were
      more than twofold lower than triclosan median effective concentration values in
      low nutrient media N:P ratios. However, a triclosan median effective
      concentration for frond number was twofold lower at N:P of 2,500 than at other
      N:P ratios in low concentration media. Influences of P enrichment on triclosan
      toxicity to L. gibba were further explored during a 14-d outdoor experimental
      stream mesocosm study. Effects of 2.6 and 20.8 microg L(-1) triclosan on L. gibba
      growth rates were more pronounced with increasing P treatment levels, which was
      generally consistent with our laboratory observations. Findings from these
      laboratory and field studies indicate that site-specific nutrient concentrations
      and ratios should be considered during assessments of primary producer responses
      to chemical stressors.

PMID- 19388794
TI  - Understanding the genetic consequences of environmental toxicant exposure:
      Chernobyl as a model system.
AB  - We sampled vole populations in Ukraine with the dual goal of characterizing
      population diversity and of providing a biogeographic perspective to evaluate
      experimental designs used for previous studies. Our data indicate that genetic
      diversity in bank vole populations is widely variable across regions and that
      diversity estimates in contaminated sites are unremarkable compared to those in
      uncontaminated areas. Furthermore, the relative frequencies of haplotypes have
      remained statistically identical throughout multiple sampling periods. Thus, the
      genetic data from bank vole populations in Ukraine fail to support the hypothesis
      that mutational changes in contaminated regions are the product of exposure to
      Chernobyl radiation. Our results suggest that genetic diversity in radioactive
      regions of Ukraine is probably a function of natural geographic variation rather
      than increased mutational pressure from radiation exposure and underscore the
      importance of adequate geographic sampling in studies designed to elucidate the
      effects of toxicant exposure.

PMID- 19388795
TI  - Can we predict the response to cyclosporine?

PMID- 19388796
TI  - Predictive factors of poor response to intravenous cyclosporine in steroid
      refractory ulcerative colitis.
AB  - BACKGROUND: The treatment of severe ulcerative colitis (UC) flares includes
      measures such as hospitalization and intravenous steroids. Despite this, a
      quarter of patients are refractory to treatment. Given the availability of new
      therapeutic strategies in patients with steroid-refractory UC (cyclosporine,
      infliximab, apheresis, surgery) it is necessary to predict which treatment will
      be most effective for each patient. OBJECTIVES: To determine which clinical or
      biological factors discriminate the lack of response to cyclosporine in steroid
      refractory UC. METHODS: Forty one flares of steroid-refractory UC in 35 patients
      treated with intravenous cyclosporine have been included. The response to
      cyclosporine was assessed at day 10 of treatment by using the modified Truelove
      and Witts disease activity score. Variables with prognostic significance were
      determined by a univariate analysis comparing groups with complete response and
      no-response, and an analysis of multiple linear regression. RESULTS: Complete
      response was obtained in 41 flares (48%), partial response in 22%, and lack of
      response in 29%. The univariate analysis showed a significant difference in four
      predictive factors: higher age (p = 0.008), thrombocytosis (p = 0.01), disease
      extent (pancolitis vs. left-sided disease (p = 0.04)), and having received
      cyclosporine previously (p = 0.01). A multiple linear regression analysis
      confirmed the significance of higher age, thrombocytosis, and having received
      cyclosporine previously as predictive factors of poor response. CONCLUSION:
      Higher age, thrombocytosis and previous use of cyclosporine predispose to poor
      response to intravenous cyclosporine in severe flares of steroid-refractory UC.

PMID- 19388797
TI  - Local excision of early rectal cancer: is transanal endoscopic microsurgery an
      alternative to radical surgery?
AB  - OBJECTIVE: Transanal endoscopic microsurgery (TEM) allows locally complete
      excision of rectal neoplasms and provides an alternative to conventional surgery
      for benign tumours. However, its role in the curative treatment of invasive
      carcinoma is controversial. This paper examines the results of TEM compared with
      radical surgery (RS) for T1 rectal cancer. METHODS: 51 patients with T1 rectal
      tumours treated by RS, or local excision by means of TEM were included. The
      following parameters were evaluated: operating time, blood loss, hospital stay
      and complications, as well as local recurrence rate and survival. RESULTS: 17
      patients were treated by RS and 34 by TEM. Operative time, blood loss, and
      duration of hospitalization were significantly lower in the TEM group compared
      with the RS group. In the RS group there were 4 patients with complications which
      required an operative revision (23.5%), compared to 1 reintervention (2.9%) in
      the TEM group. Local recurrence was 5.88% (n = 2) in the TEM group compared with
      none after RS (p = 0.547). The overall survival and disease-free survival showed
      not significant statistical differences between both groups (p = 0.59; p = 1.000,
      resp.). CONCLUSIONS: Although local recurrence was only observed after local
      excision, patients treated with TEM showed no significant differences in terms of
      overall survival and disease-free survival compared with patients who underwent
      RS. Inasmuch as local excision represents a minimally invasive technique in terms
      of morbidity, mortality and functional outcome, TEM should be offered as a valid
      option for well selected patients with early rectal cancer.

PMID- 19388798
TI  - Telomerase activity and telomere length in the colorectal polyp-carcinoma
      sequence.
AB  - OBJECTIVE: The role of telomerase activity and telomere length in the adenoma
      carcinoma sequence of colon carcinogenesis has not been well established. The
      objective of this study was to determine telomerase activity and telomere length
      patterns in patients with adenomatous polyps either associated or not with
      colorectal cancer, as well as the role of telomeric instability in the adenoma
      carcinoma sequence. PATIENTS AND METHODS: We included in the study 14 patients
      who underwent surgery for colorectal cancer and/or polyps. In 6 of these patients
      fresh samples of tumor tissue, polyps, and normal mucosa were obtained; in the 8
      remaining cases, we collected only polyps and normal mucosa. We used the
      fluorescent-telomeric repeat amplification protocol assay (TRAP-F) to determine
      telomerase activity and telomere length using Southern-blot testing. RESULTS:
      Telomerase activity was detected in 86% of polyps and 50% of associated normal
      mucosa. Mean telomerase activity in polyp tissue was 5.85; in the normal mucosa
      it was 0.58 TPG. Mean telomere length was 6.78 Kbp and 7.78, respectively. Polyps
      in patients without synchronous cancer had a telomerase activity that was
      significantly higher (9.4) than in those with cancer (1.1). CONCLUSIONS:
      Telomerase activity increases in the colorectal adenoma-carcinoma sequence,
      concurrently with a decrease in telomere length. The presence of synchronous
      cancer modifies telomerase activity in polyps.

PMID- 19388799
TI  - Results of a survey about specific inflammatory bowel disease units in Andalusia.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) has become one of the most prevalent
      pathologies in Gastroenterology Units, which added to its clinical outcome,
      treatment, the complexity of affected patients and the need to be continuously
      updated for the correct management of the disease, have made essential the
      presence of specific IBD units in each hospital. OBJECTIVES: The primary aims of
      this study were: a) to reveal the existence of these units in our area and how
      they work; and b) to draw conclusions regarding the necessary resources in these
      units and their aims. MATERIAL AND METHODS: In order to analyse the presence of
      these specialized units and the available resources in Andalusian hospitals, a 24
      question survey was designed, being answered by 11 hospitals. The evaluated
      questions included the number of days patients are attended and the number of
      physicians attending the unit, the number of available healthcare assistants, if
      emergencies are attended or not, if there is an activated telephone number for
      patient consultation, if a day care unit is available and if new treatments are
      easily accessible. RESULTS: A specific IBD unit is present in all studied
      hospitals attending more than 11 patients each, although in the 63.4% of the
      cases patients are not attended more than 3 days per week. On the other hand, the
      81.8% of the included hospitals attend emergencies although only the 54.5% of
      them had a specific telephone number for patient attendance. CONCLUSIONS: A
      specific IBD unit is present in many Andalusian hospitals, although some
      deficiencies can be observed. The general opinion of this Group is that these
      units are necessary in order to properly attend, monitorize and treat patients
      affected by IBD.

PMID- 19388800
TI  - Neuroendocrine tumors - fascination and infrequency.
AB  - In this article, I review and update of gastro-entero-pancreatic neuroendocrine
      tumors, which so much fascination have risen among healthcare providers on
      grounds of their infrequency, hormonal syndromes, and high survival rate, is
      performed based on references from the past fifteen years.

PMID- 19388801
TI  - Perianal leiomyoma.

PMID- 19388802
TI  - N-Butyl-2-cyanoacrylate plug on fundal varix: persistence 3 years after
      sclerosis.

PMID- 19388803
TI  - Effective treatment of common variable immunodeficiency associated diarrhea.
AB  - Common variable immunodeficiency disorder (CVID), the commonest symptomatic
      primary antibody deficiency syndrome, is characterised by recurrent bacterial
      infections, particularly of the upper and lower airways; it is also associated
      with an increased incidence of autoimmune and neoplastic disorders.CVID has a
      high prevalence of infectious, inflammatory and neoplastic gastrointestinal
      diseases. Up to 60% of the patients with non-treated CVID develop diarrhea and
      10% associated idiopathic malabsorption with weight loss.The case of a 50-year
      old woman with CVID-associated diarrhea, abdominal pain and bloating of one year
      s duration is reported. An exhaustive evaluation made for secondary causes of her
      symptoms was unrevealing; she was treated with loperamide and diet, without
      improvement. She later followed a course of oral budesonide for 3 months; her
      clinical symptoms disappeared and her quality of life improved.In conclusion, we
      report the case of a patient with CVID-related chronic diarrhea who responded
      well to oral budesonide treatment. This outcome provides the gastroenterologist
      with a new therapeutic option in this difficult group of patients.

PMID- 19388804
TI  - [Brain metastasis caused by colorectal carcinoma].

PMID- 19388805
TI  - [Gastrosplenic and thoracosplenic fistula due to primary untreated splenic
      lymphoma].

PMID- 19388806
TI  - [Gallstone ileus recurrence].

PMID- 19388807
TI  - [Mononucleosis syndrome of multiple etiologies in a patient with Crohn's disease
      and azathioprine treatment].

PMID- 19388808
TI  - [Relapsing colitis cystica profunda].

PMID- 19388809
TI  - [About the dawn and early steps in modern Spanish hepatology].

PMID- 19388810
TI  - Capsule endoscopy "retention" permits diagnosis of eosinophilic esophagitis.

PMID- 19388812
TI  - Mesenchymal stromal cells, colony-forming unit fibroblasts, from bone marrow of
      untreated advanced breast and lung cancer patients suppress fibroblast colony
      formation from healthy marrow.
AB  - We have shown that bone marrow (BM) from untreated advanced lung and breast
      cancer patients (LCP and BCP) have a reduced number of colony-forming unit
      fibroblasts (CFU-Fs) or mesenchymal stem cells (MSCs). Factors that regulate the
      proliferation and differentiation of CFU-F are produced by the patients' BM
      microenvironment. We have now examined whether conditioned media (CM) from
      patients' CFU-F-derived stromal cells also inhibits the colony-forming efficiency
      (CFE) of CFU-F in primary cultures from healthy volunteers (HV)-BM. Thus the
      number and proliferation potential of HV-CFU-F were also found to be decreased
      and similar to colony numbers and colony size of patients' CFU-F. Stromal cells
      from both of these types of colonies appeared relatively larger and lacked the
      characteristic spindle morphology typically seen in healthy stromal cells. We
      developed an arbitrary mesenchymal stromal cell maturational index by taking
      three measures consisting of stromal cell surface area, longitudinal and
      horizontal axis. All stromal indices derived from HV-CFU-F grown in patients' CM
      were similar to those from stromal elements derived from patients' CFU-F. These
      indices were markedly higher than stromal indices typical of HV-CFU-F cultured in
      healthy CM or standard medium [alpha-medium plus 20% heat-inactivated fetal
      bovine serum (FBS)]. Patients' CM had increased concentrations of the CFU-F
      inhibitor, GM-CSF, and low levels of bFGF and Dkk-1, strong promoters of self
      renewal of MSCs, compared to the levels quantified in CM from HV-CFU-F. Moreover,
      the majority of patients' MSCs were unresponsive in standard medium and healthy
      CM to give CFU-F, indicating that the majority of mesenchymal stromal cells from
      patients' CFU-F are locked in maturational arrest. These results show that
      alterations of GM-CSF, bFGF, and Dkk-1 are associated with deficient cloning and
      maturation arrest of CFU-F. Defective autocrine and paracrine mechanisms may be
      involved in the BM microenvironments of LCP and BCP.

PMID- 19388818
TI  - Intrathecal morphine attenuates recovery of function after a spinal cord injury.
AB  - Prior work has shown that a high dose (20 mg/kg) of systemic morphine, required
      to produce significant analgesia in the acute phase of a contusion injury,
      undermines the long-term health of treated subjects and increases lesion size.
      Moreover, a single dose of systemic morphine in the early stage of injury (24 h
      post-injury) led to symptoms of neuropathic pain 3 weeks later, in the chronic
      phase. The present study examines the locus of the effects using intrathecal
      morphine administration. Subjects were treated with one of three doses (0, 30, or
      90 microg) of intrathecal morphine 24 h after a moderate contusion injury. The 90
      microg dose produced significant analgesia when subjects were exposed to noxious
      stimuli (thermal and incremented shock) below the level of injury. Yet, despite
      analgesic efficacy, intrathecal morphine significantly attenuated the recovery of
      locomotor function and increased lesion size rostral to the injury site. A single
      dose of 30 or 90 microg of intrathecal morphine also decreased weight gain, and
      more than doubled the incidence of mortality and autophagia when compared to
      vehicle-treated controls. Morphine is one of the most effective pharmacological
      agents for the treatment of neuropathic pain and, therefore, is indispensable for
      the spinally injured. Treatment can, however, adversely affect the recovery
      process. A morphine-induced attenuation of recovery may result from increases in
      immune cell activation and, subsequently, pro-inflammatory cytokine
      concentrations in the contused spinal cord.

PMID- 19388819
TI  - Safety and availability of dapivirine (TMC120) delivered from an intravaginal
      ring.
AB  - Vaginal delivery of 200 mg or 25 mg dapivirine from intravaginal rings (IVRs) was
      evaluated over a 7-day period in two phase 1 safety trials (IPM001 and IPM008,
      respectively) in a total of 25 healthy women 19 to 46 years of age. The IVR was
      generally safe and well tolerated with similar adverse events observed in the
      placebo and dapivirine groups. Across both studies, dapivirine concentrations in
      vaginal fluids measured at the introitus, cervix, and ring area were within the
      mean range of 0.7-7.1 microg/ml. Mean dapivirine concentrations in vaginal and
      cervical tissues on day 7 were 0.3-0.7 microg/g in IPM001 and 1.5-3.5 microg/g in
      IPM008. Mean plasma concentrations of dapivirine were <50 pg/ml. Dapivirine from
      both IVRs was successfully distributed throughout the lower genital tract at
      concentrations >1000x the EC(50) against wild-type HIV-1 (LAI) in MT4 cells
      suggesting that IVR delivery of microbicides is a viable option meriting further
      study.

PMID- 19388820
TI  - HIV type 1 drug resistance in adults receiving highly active antiretroviral
      therapy in Abidjan, Cote d'Ivoire.
AB  - As antiretroviral therapy continues to scale-up in developing countries, there is
      concern that high levels of HIV drug resistance to antiretroviral drugs will
      occur. Here we describe rates of emergence of HIV-1 drug resistance and factors
      associated with their occurrence among adults who received antiretroviral therapy
      (ART) for >1 year through the Cote d'Ivoire national drug access program from
      1998 to 2003. To detect genotypic drug resistance, we sequenced all 1- and 2-year
      specimens with detectable HIV RNA viral load. To assess factors associated with
      emerging drug resistance, we used log normal regression with interval censoring,
      including covariates in the model for self-reported drug adherence, CD4 cell
      count, and HIV viral load at therapy initiation, and observed changes in these
      measures, type of prescribed ART drugs, diagnoses of opportunistic illness, and
      demographic characteristics. An estimated 14.2% [95% confidence limits (CL) 11.7,
      16.9] and 26.6% (95% CL 22.7, 30.8) of patients developed primary drug-resistant
      mutations within 1 year and 2 years after initiation of therapy, respectively.
      Factors associated with drug resistance included drug nonadherence, partial or
      lack of viral suppression, higher viral load or lower CD4 at initiation of
      therapy, and initiation of ART with what is now considered substandard dual
      combination therapy. Our results demonstrate the need to strengthen adherence and
      continuity in treatment programs in order to avoid interruption of ART drugs.
      Treatment programs should pay attention to indicators of emerging drug
      resistance: incomplete or lesser decreases in viral load or increases in CD4 cell
      counts following initiation of therapy, and the occurrence of AIDS opportunistic
      illnesses.

PMID- 19388821
TI  - Translation-linked mRNA destabilization accompanying serum-induced Nox4
      expression in human endothelial cells.
AB  - NADPH oxidase is involved in cell signaling, regulating proliferation of vascular
      cells, especially in endothelium. The Nox4 catalytic subunit has a major role in
      endothelial cells, but growth arrest of cultured endothelial cells following
      serum deprivation paradoxically increases mRNA for Nox4. We investigated the
      relationships between Nox4 mRNA stability and protein expression in human
      microvascular endothelial cells. Serum starvation increased the steady-state
      level of Nox4 mRNA but paradoxically diminished Nox4 protein expression. mRNA
      transcription in the absence of serum is maintained by the p38MAP kinase pathway,
      for inhibition of p38MAP kinase reduced both Nox4 mRNA and Nox4 promoter
      activity. In serum-starved cells, reintroduction of serum increased Nox4 protein
      levels within 30 min and up to 24 h. In contrast, the mRNA decreased equally
      rapidly after serum stimulation. Inhibition of Nox4 translation by cycloheximide
      blocked serum-induced mRNA degradation and Nox4 protein synthesis, and
      actinomycin-D also delayed Nox4 mRNA decay. Therefore, Nox4 mRNA level falls
      after serum stimulation because of a translation-initiated mRNA destabilization
      program. Clearly Nox4 mRNA is regulated at both transcriptional and post
      transcriptional levels, and the steady state level of Nox4 mRNA does not
      accurately reflect Nox4 protein abundance and functions, with implications for
      regulation of cell proliferation and survival.

PMID- 19388822
TI  - High frequency of gross deletions in 5' LTR/gag and nef genes in patients
      infected with CRF02_AG of HIV type 1 who survived for over 20 years: an
      association with Korean red ginseng.
AB  - Abstract We have shown that Korean red ginseng (KRG) intake is associated with
      gross deletions in the 5' LTR/gag (gDeltaLTR/gag) and nef genes (gDeltanef) of
      patients infected with subtype B of HIV-1. Here, we investigated these effects in
      three long-term survivors (LTSs) of subtype CRF02_AG of HIV-1. The three LTSs
      were diagnosed with HIV in 1987, 1988, and 1989, and have been treated with KRG
      for 7-15 years. Thirty-two samples of peripheral blood mononuclear cells were
      obtained from the subjects and used to amplify the 5' LTR/gag and nef genes via
      nested PCR. We obtained 88 amplicons in 5' LTR/gag and 128 amplicons in nef. The
      frequency of gDeltaLTR/gag was significantly higher (37.5%) in three LTSs than in
      control patients (8.6%, p < 0.01). Eight amplicons (9.5%) contained premature
      stop codon(s) in the gDeltaLTR/gag in three LTSs. Fourteen of the 128 nef
      amplicons (10.9%) contained the gDeltanef, which was present in only two (7.7%)
      of the 26 amplicons from control subjects. Interestingly, gDeltanef was detected
      7 years after the reinitiation of KRG intake in an LTS and, coincidently, CD4 T
      cell counts and CD4/CD8 ratios rapidly increased. These data indicate that long
      term intake of KRG has the therapeutic potential to induce gross deletions in HIV
      1.

PMID- 19388823
TI  - Low prevalence of drug resistance transmitted virus in HIV Type 1-infected ARV
      naive patients in Cambodia.
AB  - Abstract Between November 2006 and June 2007, HIV-1 reverse transcriptase (RT)
      and protease (PR) genes of 67 ARV-naive Cambodian patients were amplified and
      sequenced. At inclusion, the median age and duration of HIV infection were 28 and
      1.1 years, respectively. The median CD4 and HIV-1 RNA were 611 cells/ml [IQR: 525
      759] and 4.0 log(10) copies/ml [IQR: 3.4-4.6]. Among 67 HIV-1 strains, 95.5% were
      CRF 01_AE viruses (n = 64) whereas three clustered with subtype B. RT analysis
      indicated that only 1 patient out of 67, presenting K103N and M184V mutations,
      was resistant to NVP/EFV and 3TC/FTC. No primary resistance to protease
      inhibitors was detected in 59 amplified protease genes. The 1.49% (IC 95%: 0.04
      8.04%) prevalence of transmitted drug-resistant strains in drug-naive patients
      was low in our study. Surveys of drug-resistant transmitted viruses should be
      regularly performed regarding the increasing access to HAART in Cambodia.

PMID- 19388824
TI  - Mechanisms and implications of reactive oxygen species generation during the
      unfolded protein response: roles of endoplasmic reticulum oxidoreductases,
      mitochondrial electron transport, and NADPH oxidase.
AB  - Cellular mechanisms governing redox homeostasis likely involve their integration
      with other stresses. Endoplasmic reticulum (ER) stress triggers complex adaptive
      or proapoptotic signaling defined as the unfolded protein response (UPR),
      involved in several pathophysiological processes. Since protein folding is highly
      redox-dependent, convergence between ER stress and oxidative stress has attracted
      interest. Evidence suggests that ROS production and oxidative stress are not only
      coincidental to ER stress, but are integral UPR components, being triggered by
      distinct types of ER stressors and contributing to support proapoptotic, as well
      as proadaptive UPR signaling. Thus, ROS generation can be upstream or downstream
      UPR targets and may display a UPR-specific plus a nonspecific component.
      Enzymatic mechanisms of ROS generation during UPR include: (a) Multiple thiol
      disulfide exchanges involving ER oxidoreductases including flavooxidase Ero1 and
      protein disulfide isomerase (PDI); (b) Mitochondrial electron transport; (c) Nox4
      NADPH oxidase complex, particularly Nox4. Understanding the roles of such
      mechanisms and how they interconnect with the UPR requires more investigation.
      Integration among such ROS sources may depend on Ca(2+) levels, ROS themselves,
      and PDI, which associates with NADPH oxidase and regulates its function.
      Oxidative stress may frequently integrate with a background of ER stress/UPR in
      several diseases; here we discuss a focus in the vascular system.

PMID- 19388825
TI  - Allantoin in human plasma, serum, and nasal-lining fluids as a biomarker of
      oxidative stress: avoiding artifacts and establishing real in vivo
      concentrations.
AB  - Urate is the terminal product of purine metabolism in primates, including humans.
      Urate is also an efficient scavenger of oxidizing species and is thought to be an
      important antioxidant in human body fluids. Allantoin, the major oxidation
      product of urate, has been suggested as a candidate biomarker of oxidative stress
      because it is not produced metabolically. Although urate is converted to
      allantoin under strongly alkaline pH, such conditions have been used in the past
      to facilitate extraction of allantoin. We evolved a method for the determination
      of allantoin concentrations in human plasma and serum by gas chromatography-mass
      spectrometry without such artifact. With this method, we show that alkaline
      conditions do indeed cause breakdown of urate, leading to significant
      overestimation of allantoin concentration in human samples. By using our
      alternative method, serum samples from 98 volunteers were analyzed, and allantoin
      levels were found to be significantly lower than was previously reported. The in
      vivo utility and sensitivity of our method was further evaluated in human nasal
      lining fluids. We were able to demonstrate an ozone-induced increase in
      allantoin, in the absence of increases in either ascorbate or glutathione
      oxidation products.

PMID- 19388826
TI  - A role for protein disulfide isomerase in the early folding and assembly of MHC
      class I molecules.
AB  - Proper folding and assembly of major histocompatibility complex (MHC) class I
      complexes are essential for optimal peptide loading and subsequent antigen
      presentation. MHC class I folding involves the coordinated formation of multiple
      disulfide bonds within MHC class I molecules. However, the regulation of
      disulfide bond formation during the early process of MHC class I folding is
      uncharacterized. Here, we show that protein disulfide isomerase (PDI) catalyzes
      the disulfide bond formation of MHC class I molecules and thereby facilitates the
      assembly of MHC class I heavy chain with beta(2)-microglobulin (beta(2)m).
      Depletion of PDI but not ERp57 by RNAi interfered with the disulfide bond
      formation in the MHC class I molecules. In the absence of PDI, the association of
      free class I heavy chain with calnexin increased, whereas the assembly of MHC
      class I heavy chain-beta(2)m heterodimers was delayed. These observations suggest
      that PDI-catalyzed disulfide bond formation of MHC class I molecules is an event
      downstream of the interaction of class I molecules with calnexin and upstream of
      their interaction with beta(2)m. Thus, our data establish a critical function for
      PDI in the early assembly of MHC class I molecules.

PMID- 19388827
TI  - Adhesion and growth inhibitory effect of chicken egg yolk antibody (IgY) on
      Salmonella enterica serovars Enteritidis and Typhimurium in vitro.
AB  - The protective effects of powder preparation of egg yolk immunoglobulin Y (IgY),
      specific to Salmonella Enteritidis and Salmonella Typhimurium outer membrane
      proteins (OMP), against these two Salmonella sp. serovars were investigated in
      vitro in two different assays: adhesion-prevention and growth-inhibition. The
      adhesion-prevention assay was conducted using polarized monolayers of the human
      intestinal epithelial Caco-2 cell line. First, the conditions of Salmonella
      adherence to Caco-2 cells were optimized, and interferences of bacteria with the
      transepithelial electrical resistance (TER) of fully differentiated Caco-2 cell
      monolayers and the lactate dehydrogenase release upon exposure of the cells to
      Salmonella were evaluated. Both Salmonella sp. serovars were able to adhere to
      Caco-2 cells and decreased TER. Results from the adhesion-prevention assay
      demonstrated that specific IgY reduced the decrease in TER of the infected Caco-2
      cell monolayers and blocked the Salmonella sp. adhesion in a concentration
      dependent manner (p < 0.05). Nonspecific IgY also exhibited an inhibitory effect
      on these two parameters, but to a lesser extent than that of the specific IgY (p
      < 0.05). The protective effect of nonspecific IgY could be attributed to the low
      density lipoprotein component of the water-soluble fraction of egg yolks that may
      not have been eliminated during ultrafiltration. The growth-inhibition assay
      revealed that specific IgY had an inhibitory effect on the bacterial growth,
      markedly during the late exponential phase, whereas nonspecific IgY failed to do
      so. Taken together, these results suggest that the in vitro growth inhibitory
      effect of specific IgY on Salmonella spp. resulted from the specific binding
      activity of these IgY to Salmonella sp. OMP. Passive immunization with Salmonella
      sp. OMP-specific IgY could thus be useful to prevent Salmonella colonization in
      broiler chickens and the subsequent carcass contamination during processing.

PMID- 19388828
TI  - Association between a case study of asymptomatic ovine listerial mastitis and the
      contamination of soft cheese and cheese processing environment with Listeria
      monocytogenes in Portugal.
AB  - For 5 months, the udders of milking ewes, raw ewe's milk, cheese, and the plant
      and environment of a cheese manufacturer in Portugal were investigated using
      standard methods for the presence of Listeria spp. An association between
      subclinical mastitis and Listeria monocytogenes in a single lactating sheep was
      investigated by visual inspection of udders for signs of inflammation,
      application of somatic cell counts, the California mastitis test, pH measurement
      to milk, and culture of L. monocytogenes and Staphylococcus spp. To track the
      routes of contamination by L. monocytogenes, 103 isolates were characterized by
      molecular serotyping and amplified fragment length polymorphism, and a selection
      was further tested by pulsed-field gel electrophoresis. This study provides
      molecular and epidemiological evidence tracking the persistence of a single L.
      monocytogenes strain causing a subclinical udder infection without obvious
      inflammation in a single ewe. This infection was the likely source of
      contamination of raw milk that was subsequently used to produce unpasteurised
      milk cheese and resulted in a single strain of this bacterium colonizing the
      processing environment and the final cheese product.

PMID- 19388829
TI  - The ability of Campylobacter jejuni cells to attach to stainless steel does not
      change as they become nonculturable.
AB  - The ability of Campylobacter jejuni strains to attach to stainless steel as they
      became nonculturable during storage in distilled water at 4 degrees C for 30 days
      was investigated. From an initial count of approximately 7 log colony-forming
      units/mL all strains completely lost culturability by day 20, but the numbers of
      cells attaching to stainless steel remained constant at approximately 3.5 log
      cells/cm(2). These findings suggest that viable but nonculturable Campylobacter
      in a liquid matrix can still attach to stainless steel.

PMID- 19388830
TI  - Molecular characterization of tetracycline-resistant genes and integrons from
      avirulent strains of Escherichia coli isolated from catfish.
AB  - A study was undertaken to investigate the occurrence of tetracycline-resistant
      genes and to characterize the integrons present in Escherichia coli isolated from
      catfish. Sixty-three tetracycline-resistant E. coli strains were isolated from
      the intestinal contents of 407 farm-raised catfish. All strains were resistant to
      multiple antibiotics. A polymerase chain reaction (PCR) assay detected tetA in
      the DNA of 15 of 63 (25.0%) isolates by amplifying a PCR amplicon measuring 957
      bp. Oligonucleotide primers targeting a 436-bp region of tetB successfully
      amplified a PCR amplicon from 47 of 63 (77.0%) isolates, indicating that tetB was
      predominant. Oligonucleotide primers specific for tetC amplified a 589-bp PCR
      amplicon from 3 of 63 (5%) isolates. Eleven (17.0%) of the isolates contained
      both tetA and tetB genes. Class I integrons amplified from the genomic DNA of 14
      of 63 (22.0%) isolates measured 1.6 and 1.8 kb. Sequence analysis of the 1.6 kb
      integrons indicated the presence of three different gene cassettes: a dfrA12,
      conferring resistance to trimethoprim; an open reading frame, orfF, a
      hypothetical protein of unknown function; and aadA2, conferring resistance to
      aminoglycosides. Sequence analysis of the 1.8-kb integron indicated the presence
      of dfrA17 and aadA5. PCR assays for the detection of the six predominant
      virulence genes failed to amplify any genes from the genomic DNA. Pulsed-field
      gel electrophoresis using XbaI identified 16 distinct macro restriction patterns
      among the 63 isolates. The dendrogram analysis indicated that the DNA from 4 of
      16 isolates had a similarity index of 90.0%. Our results indicate that the use of
      oxytetracycline and Romet 30 (sulfadimethoxine and ormetoprim) in farm-raised
      catfish may select for multiple antibiotic-resistant E. coli that could serve as
      a reservoir of tetracycline, trimethoprim, and aminoglycoside resistance genes.

PMID- 19388831
TI  - Survival and growth of Salmonella Enteritidis in liquid egg products varying by
      temperature, product composition, and carbon dioxide concentration.
AB  - Cryogenic cooling of shell eggs with carbon dioxide (CO(2)) is known to improve
      egg content quality through rapid cooling as well as by increasing internal CO(2)
      levels. A study was undertaken to determine the effects of variations in
      atmospheric CO(2) concentrations (aerobically stored, flushed with CO(2) and
      sealed, or bubbled with CO(2)) on the survival and growth of Salmonella
      Enteritidis in liquid egg products including whole egg, albumen, yolk, and
      albumen + 1% yolk. Egg products were inoculated with a three-strain composite of
      Salmonella Enteritidis at ca. 4 log colony-forming units (CFU)/mL and stored at 7
      degrees C or 10 degrees C for 8 or 4 days, respectively, or at ca. 2 log CFU/mL
      and stored at 23 degrees C and 37 degrees C for 48 or 24 hours, respectively.
      Salmonella populations differed based on variations in liquid egg composition (p
      < 0.05). Manipulating the atmospheric concentrations of CO(2) in which liquid egg
      products were stored did not significantly inhibit the growth of Salmonella
      Enteritidis (p > 0.05) in yolk-containing egg products or affect the inhibitory
      activity of albumen-containing products. Populations of Salmonella were static at
      7 degrees C over the entire storage period and significant growth occurred in
      whole egg and yolk stored at 10 degrees C. Populations in egg stored at 23
      degrees C and 37 degrees C were greater in yolk than in whole egg, although whole
      egg had populations greater than in albumen or albumen +1% yolk (p < 0.05).
      Results of this investigation suggest that increasing atmospheric CO(2) to
      enhance egg quality should not promote the growth of Salmonella Enteritidis in
      eggs.

PMID- 19388832
TI  - Inactivation of Salmonella Enteritidis in chicken breast fillets by single-cycle
      and multiple-cycle high pressure treatments.
AB  - The effect of single-cycle and multiple-cycle high hydrostatic pressure (HHP)
      treatments on the survival of three Salmonella Enteritidis strains in chicken
      breast fillets was investigated. The surface of fillets was inoculated with a
      cocktail of three Salmonella strains at approximately 10(7) colony-forming units
      (CFU)/g, and held at 4 degrees C for 20 hours before HHP treatments. Reduction of
      Salmonella counts on tryptic soy agar (TSA) by single-cycle treatments at 300 MPa
      and 12 degrees C ranged from 0.58 log CFU/g for a 0-minute (no dwell time) cycle
      to 3.35 log CFU/g for a 20-minute cycle, whereas with 400 MPa treatments the
      decline ranged from 0.93 log CFU/g to more than 5 log CFU/g, respectively. The
      4.8 log unit reduction in Salmonella counts on TSA achieved by a 15-minute
      treatment at 400 MPa should suffice to eliminate the pathogen naturally present
      in contaminated chicken meat. When plated on Salmonella Shigella agar (SSA), the
      reduction of Salmonella counts by single-cycle treatments at 300 MPa and 12
      degrees C ranged from 0.69 log CFU/g for a 0-minute cycle to 4.21 log CFU/g for a
      20-minute cycle, and with 400 MPa treatments from 1.25 log CFU/g to more than 5
      log CFU/g, respectively. From the comparison of Salmonella counts on SSA and TSA
      it was concluded that not only the lethality but also the proportion of injured
      Salmonella cells increased with the length of HHP treatments. The use of multiple
      cycle treatments instead of single-cycle treatments of the same HHP time for the
      inactivation of Salmonella Enteritidis inoculated on chicken breast fillets
      showed to be more advantageous at 400 MPa than at 300 MPa. No recovery of injured
      Salmonella cells was observed when fillets treated at 300 or 400 MPa for 5
      minutes were held for 72 hours at 4 degrees C.

PMID- 19388833
TI  - Murine preosteoblast differentiation induced by a peptide derived from bone
      morphogenetic proteins-9.
AB  - Bone morphogenetic proteins (BMPs) increase the differentiation of osteoblasts
      implicated in bone formation and repair. In a previous study, we demonstrated
      that a peptide derived from BMP-9 (pBMP-9) at 400 ng/mL inhibited murine
      preosteoblasts MC3T3-E1 proliferation. Here, we compared the effects of equimolar
      concentrations of BMP-2 (50 ng/mL), BMP-9 (42.3 ng/mL), and pBMP-9 (4.52 ng/mL)
      on the differentiation of MC3T3-E1 in a serum-free medium. Like BMP-2, BMP-9 and
      pBMP-9 activated the Smad pathway. In contrary to BMP-2, the Smad phosphorylation
      induced by BMP-9 and pBMP-9 is not prevented by noggin, an extracellular
      antagonist of BMP-2. Further, BMP-9 and pBMP-9 increased, dose dependently,
      alkaline phosphatase activity, an early marker of osteoblast differentiation,
      after 1 day. Quantitative real-time polymerase chain reaction analysis
      demonstrated that BMP-2, BMP-9, and pBMP-9 (4.52 or 400 ng/mL) all activated the
      transcription of Runx2, Osterix, type I collagen alpha1 chain, and Osteocalcin
      genes within day 6. Alizarin red S quantification demonstrated that pBMP-9 (400
      ng/mL) and pBMP-9 (4.52 ng/mL) allowed a slight deposition of Ca(2+) in the
      extracellular matrix of cells within 12 and 18 days, respectively. Therefore,
      pBMP-9 might be a promising replacement for costly BMP in tissue engineering
      applications that require a well-defined serum-free medium.

PMID- 19388835
TI  - Management strategy for dirty abdominal incisions: primary or delayed primary
      closure? A randomized trial.
AB  - BACKGROUND AND PURPOSE: It is still a matter of debate whether delayed primary
      closure (DPC) of dirty abdominal incisions reduces surgical site infections
      (SSIs) compared with primary closure (PC). Our objective was to determine whether
      DPC of dirty abdominal incisions reduces SSIs. METHOD: A controlled randomized
      study was conducted at an academic tertiary care 1,500-bed university hospital in
      Western India involving 81 consecutive patients with dirty abdominal incisions.
      Only 77 patients (DPC = 37, PC = 40) were evaluable because of the deaths of four
      patients. A total of 52 patients had peptic or typhoid perforations, whereas the
      rest had appendicular perforations/abscesses, penetrating or blunt abdominal
      injuries with gastrointestinal perforation, or intra-peritoneal abscesses.
      Patients were randomized to have their surgical incisions (skin and subcutaneous
      tissue) either closed primarily (PC) or left open with saline-soaked gauze
      dressings for DPC on the 3(rd) postoperative day or later if the incision
      conditions were inappropriate for closure. The main outcome measure was the
      incidence of postoperative SSI. RESULTS: In the entire series, SSI developed
      after incision closure in 23% of the patients. Infections were significantly more
      common in the PC group (42.5% vs. 2.7% for DPC; p = 0.0000375). There also were
      significantly more cases of abdominal dehiscence in the PC group (DPC 1 [2.7%]
      vs. PC 10 [25%]; p = 0.005). The mean complete incision healing (CIH) time and
      length of hospital stay (LOS) were longer after PC (18.52 days) than DPC (13.86
      days), resulting in a significant difference in the end point of healing and LOS
      (p = 0.0207). Short-term cosmetic results for PC incisions were significantly
      inferior to those for DPC (p = 0.03349). CONCLUSIONS: Delayed primary closure is
      a sound incision management technique that should be utilized for dirty abdominal
      incisions. It significantly lowers the rate of superficial SSI as well as fascial
      dehiscence and reduces the mean CIH time and hospitalization. The short-term
      cosmetic appearance is superior.

PMID- 19388834
TI  - Efficient derivation of alveolar type II cells from embryonic stem cells for in
      vivo application.
AB  - In the present study, mouse embryonic stem cells (ESCs) were differentiated into
      alveolar epithelial type II (AEII) cells for endotracheal injection. These
      enriched lung-like populations expressed lung epithelial markers SP-A, SP-B, SP
      C, and CC10. First we show that rapid differentiation of ESCs requires a
      dissociated seeding method instead of an embryoid body culture method. We then
      investigated a two-step differentiation of ESCs into definitive endoderm by
      activin or A549-conditioned medium as a precursor to lung epithelial cells. When
      conditioned medium from A549 cells was used to derive endoderm, yield was
      increased above that of activin alone. Further studies showed that Wnt3a may be
      one of the secreted factors produced by A549 cells and promotes definitive
      endoderm differentiation, in part, through suppression of primitive endoderm.
      Activin and Wnt3a together at appropriate doses with dissociated cell seeding
      promoted greater endoderm yield than activin alone. Next, fibroblast growth
      factor 2 was shown to induce a dose-dependent expression of SPC, and these cells
      contained lamellar bodies characteristic of mature AEII cells from ESC-derived
      endoderm. Finally, ES-derived lung cells were endotracheally injected into
      preterm mice with evidence of AEII distribution within the lung parenchyma. This
      study concludes that a recapitulation of development may enhance derivation of an
      enriched population of lung-like cells for use in cell-based therapy.

PMID- 19388836
TI  - Obesity and site-specific nosocomial infection risk in the intensive care unit.
AB  - BACKGROUND: Obese patients are at higher than normal risk for postoperative
      infections such as pneumonia and surgical site infections, but the relation
      between obesity and infections acquired in the intensive care unit (ICU) is
      unclear. Our objective was to describe the relation between body mass index (BMI)
      and site-specific ICU-acquired infection risk in adults. METHODS: Secondary
      analysis of a large, dual-institutional, prospective observational study of
      critically ill and injured surgical patients remaining in the ICU for at least 48
      h. Patients were classified into BMI groups according to the National Heart, Lung
      and Blood Institute guidelines: <or= 18.5 kg/m(2) (underweight), 18.5-24.9
      kg/m(2) (normal), 25-29.9 kg/m(2) (overweight), 30.0-39.9 kg/m(2) (obese), and
      >or= 40.0 kg/m(2) (severely obese). The primary outcomes were the number and site
      of ICU-acquired U.S. Centers for Disease Control and Prevention-defined
      infections. Multivariable logistic and Poisson regression were used to determine
      age-, sex-, and severity-adjusted odds ratios (ORs) and incidence rate ratios
      associated with differences in BMI. RESULTS: A total of 2,037 patients had 1,436
      infection episodes involving 1,538 sites in a median ICU length of stay of 9
      days. After adjusting for age, sex, and illness severity, severe obesity was an
      independent risk factor for catheter-related (OR 2.2; 95% confidence interval
      [CI] 1.5, 3.4) and other blood stream infections (OR 3.2; 95% CI 1.9, 5.3).
      Cultured organisms did not differ by BMI group. CONCLUSION: Obesity is an
      independent risk factor for ICU-acquired catheter and blood stream infections.
      This observation may be explained by the relative difficulty in obtaining venous
      access in these patients and the reluctance of providers to discontinue
      established venous catheters in the setting of infection signs or symptoms.

PMID- 19388837
TI  - Clostridium perfringens liver abscess after pancreatic resection.
AB  - BACKGROUND: Liver abscess is a rare complication after pancreatectomy.
      Clostridium perfingens is a rare cause of intrahepatic infections. CASE REPORT: A
      65-year-old woman with pancreatic cancer underwent explorative laparotomy, during
      which encasement of the hepatic artery by the tumor was found. Neoadjuvant
      radiochemotherapy with capecitabine was started, which caused tumor regression,
      and duodenopancreatectomy was performed. The portal vein was occluded and
      infiltrated by cancer and therefore was resected and not reconstructed. After a
      slow recovery, the patient developed hemorrhage at the gastrojejunal anastomosis,
      which was controlled by fibrin injection. Within a few days, she presented with
      signs of sepsis, and blood cultures yielded Clostridium perfringens,
      Streptococcus oralis, Staphylococcus aureus, and Candida albicans. The source of
      the sepsis proved to be a 9-cm liver abscess, which was drained; cultures grew C.
      perfringens, Hafnia alvei, and Enterobacter cloacae. Despite antibiotic
      treatment, the patient died from sepsis and multiorgan failure 27 days after
      pancreatic surgery. CONCLUSION: Such rare infections can follow pancreatic
      resection with neoadjuvant radiochemotherapy. Clostridium perfringens-associated
      liver abscess maintains a high mortality rate.

PMID- 19388838
TI  - Need for both antibiotic cycling and stringent environmental controls to prevent
      Pseudomonas infections.

PMID- 19388844
TI  - Highlights from the May 2009 issue of DNA and Cell Biology.

PMID- 19388846
TI  - Posttranscriptional regulatory elements enhance antigen expression and DNA
      vaccine efficacy.
AB  - In higher eukaryotes, introns are usually required for efficient pre-mRNA
      processing. However, some viruses have alternative approaches involving
      posttranscriptional regulatory elements (PREs) to enhance intronless heterologous
      gene expression through enabling stability and 3' end formation, and to
      facilitate the nucleocytoplasmic export of unspliced mRNAs. In the current study,
      we compared the human cytomegalovirus (hCMV) immediate/early (IE) intronA, as
      well as virus-derived PREs-the PRE of Hepatitis B virus (HPRE) and Woodchuck
      Hepatitis virus (WPRE) on their ability to enhance antigen gene expression in
      vitro and immune responses induced by DNA vaccination in animal. Among all the
      constructs, the plasmids carrying the HPRE element showed the highest gene
      expression level in both in vivo and in vitro models. During immunization of mice
      with low doses (10 microg) of HIV-1 DNA vaccine, only -intronA/+HPRE and
      +intronA/+HPRE vaccine constructs induced anti-Gag antibodies, although the 
      intronA/+WPRE construct also elicited antigen-specific cellular immune responses.
      In addition, pInHGag (+intronA/+HPRE) at a 10 mug dose could induce higher anti
      Gag antibody level than that induced by pGag (-intronA/-HPRE) or pInGag
      (+intronA/-HPRE) at 40 microg dose (p < 0.05). Our data are useful for the
      optimization of heterologous expression and immunogenicity of DNA vaccines.

PMID- 19388845
TI  - DNA Methyltransferase protein synthesis is reduced in CXXC finger protein 1
      deficient embryonic stem cells.
AB  - CXXC finger protein 1 (CFP1) binds to unmethylated CpG dinucleotides and is
      required for embryogenesis. CFP1 is also a component of the Setd1A and Setd1B
      histone H3K4 methyltransferase complexes. Murine embryonic stem (ES) cells
      lacking CFP1 fail to differentiate, and exhibit a 70% reduction in global genomic
      cytosine methylation and a 50% reduction in DNA methyltransferase (DNMT1) protein
      and activity. This study investigated the underlying mechanism for reduced DNMT1
      expression in CFP1-deficient ES cells. DNMT1 transcript levels were significantly
      elevated in ES cells lacking CFP1, despite the observed reduction in DNMT1
      protein levels. To address the posttranscriptional mechanisms by which CFP1
      regulates DNMT1 protein activity, pulse/chase analyses were carried out,
      demonstrating a modest reduction in DNMT1 protein half-life in CFP1-deficient ES
      cells. Additionally, global protein synthesis was decreased in ES cells lacking
      CFP1, contributing to a reduction in the synthesis of DNMT1 protein. ES cells
      lacking CFP1 were found to contain elevated levels of phosphorylated eIF2alpha,
      and an accompanying reduction in translation initiation as revealed by a lower
      level of polyribosomes. These results reveal a novel role for CFP1 in the
      regulation of translation initiation, and indicate that loss of CFP1 function
      leads to decreased DNMT1 protein synthesis and half-life.

PMID- 19388847
TI  - Lead-, cadmium-, and arsenic-induced DNA damage in rat germinal cells.
AB  - Toxic agents can interfere with the male reproductive system at many targets. One
      of the major unresolved questions concerning male infertility is identification
      of its molecular origins. Clinical and animal studies indicate that abnormalities
      of spermatogenesis result from exposure to three toxic metals (lead acetate,
      cadmium chloride, and arsenic trioxide), but the effects on primary spermatocyte
      DNA of the male rat after chronic exposure to these metals have not been
      identified. The aims of this study were to analyze, in three independent
      experiments, the DNA damage induced by lead (Pb), cadmium (Cd), and arsenic (As)
      in rat germinal cells during three time periods, and to determine the
      relationship between DNA damage and blood Pb, blood Cd, and urine As levels. For
      lead acetate and cadmium chloride experiments, blood was collected by cardiac
      puncture, while for arsenic trioxide a 24-h urine sample was collected.
      Afterward, the animals were sacrificed by decapitation. Pachytene spermatocytes
      from rat testes were purified by trypsin digestion followed by centrifugal
      elutriation. After establishment of cell purity and viability, DNA damage (tail
      length) was measured employing a single cell gel/comet assay. Significant DNA
      damage was found in primary spermatocytes from rats with chronic exposure (13
      weeks) to toxic metals. In conclusion, these findings indicate that exposure to
      toxic metals affects primary spermatocyte DNA and are suggestive of possible
      direct testicular toxicity.

PMID- 19388848
TI  - Association among IRF6 polymorphism, environmental factors, and nonsyndromic
      orofacial clefts in western china.
AB  - The interferon regulatory factor 6 (IRF6) gene and environmental factors have
      been shown to be associated with nonsyndromic cleft lip with or without cleft
      palate (NSCL/P) in several populations. This study aimed to confirm the
      contribution of IRF6 and environmental factors to NSCL/P risk in western Han
      Chinese. Five single nucleotide polymorphisms (SNPs) were investigated in 107
      case trios (child and parents) and 100 normal peers in western China using
      transmission disequilibrium test, case-control analysis, and logistic regression
      models. Strong evidence of linkage disequilibrium was found between these markers
      and the disease in both SNP analysis (A allele at rs4844880, G allele at
      rs2073485, and C allele at rs599021) and haplotype analysis (A-A for rs861019 and
      rs4844880, A-C for rs4844880 and rs599021, among others). Both mothers'
      medication and passive smoking during the first trimester of pregnancy may
      increase the risk of NSCL/P, but mothers' vitamins (including folic acid)
      supplementation during the first trimester was a protective factor. Interactions
      between mothers' abortion history and TT genotype of rs2235373 were statistically
      significant (odds ratio = 6.70, 95% confidence interval =1.69-26.52). Risk
      factors identified in this study may provide a better understanding of the
      etiological role IRF6 and environmental factors play in NSCL/P incidence.

PMID- 19388849
TI  - Association of C3435T single-nucleotide polymorphism of MDR1 gene with breast
      cancer in an Iranian population.
AB  - The human multidrug resistance gene 1 (MDR1) encodes a plasma membrane, P
      glycoprotein (Pgp), which functions as the transmembrane efflux pump for various
      structurally unrelated anticancer agents and toxins. Polymorphisms in the MDR1
      gene may have an impact on the expression and function of Pgp, thereby
      influencing the susceptibility to various diseases, including cancer. Recently, a
      silent C3435T polymorphism in exon 26 of MDR1 has been reported to be associated
      with decreased expression of Pgp in TT genotype carriers and thus it may alter
      the physiological protective role of Pgp and influence disease risk. To evaluate
      the association of this polymorphism with breast cancer, 106 patients with breast
      cancer and 77 healthy controls were enrolled in this study. They were visited at
      two centers during a 1-year period (2006-2007). Data about the risk factors of
      breast cancer were collected using questionnaires. DNA of the whole-blood sample
      was extracted, and the polymorphic fragment was amplified by polymerase chain
      reaction using specific primers. The C3435T polymorphism was detected by the
      restriction fragment length polymorphism method. There were no significant
      differences in genotype (p = 0.744) and allele (p = 0.590) frequencies between
      patients and control subjects. Moreover, distribution of the breast cancer
      patients' risk factors was not different among CC, CT, and TT genotypes. Our
      results suggest that C3435T MDR1 polymorphism was not associated with the
      susceptibility to breast cancer in the population studied.

PMID- 19388850
TI  - Epidermal growth factor genetic variation, breast cancer risk, and waiting time
      to onset of disease.
AB  - Growth factors are important mediators of proliferation. Deregulation in growth
      factor mechanisms as well as in its receptors will contribute to cancer
      development. One of the most important is the epidermal growth factor (EGF),
      which is encoded by EGF gene. A functional polymorphism at position 61 (A/G) is
      associated with increased expression of EGF. Thus, we proposed to assess genotype
      frequencies in a case-control study and appraise their association to breast
      cancer risk. Using the polymerase chain reaction technique combined with
      restriction enzyme fragment length polymorphism (PCR-RFLP) we analyzed DNA from
      883 women (500 controls and 383 breast cancer patients). Our results suggested
      that carriers of G homozygous genotype had a lower risk for developing breast
      cancer (odds ratio = 0.68; 95% confidence intervals, 0.46-1.01). Further, we
      showed that the waiting time for onset of breast cancer in G homozygous patients
      for EGF genotypes (55 years) was significantly lower in comparison to A-allele
      carriers (59 years) (log-rank test: p = 0.038). EGF is produced in mammary tissue
      and acts in the mammalian development. A lower risk for breast cancer in GG
      carriers might be explained through EGF receptor internalization promoted by EGF.

PMID- 19388851
TI  - Human TRIM5alpha expression levels and reduced susceptibility to HIV-1 infection.
AB  - BACKGROUND: Human TRIM5alpha (TRIM5alphahu), a member of the tripartite motif
      protein family, displays some anti-human immunodeficiency virus type 1 (HIV-1)
      activity in vitro, although it is substantially less potent than its rhesus
      monkey counterpart (TRIM5alpharh). The effects of levels of TRIM5alphahu on
      prevention or control of HIV-1 infection in vivo are unknown. METHODS: We used a
      quantitative real-time polymerase chain reaction (PCR) assay to measure levels of
      TRIM5alphahu expression in peripheral blood mononuclear cells (PBMCs) obtained
      from a cohort of individuals at high risk for HIV-1 infection in Durban, South
      Africa. Samples were available from 38 infected subjects (with all these samples
      obtained within 1 year of infection) and from 57 uninfected persons. Matched
      preinfection and postinfection samples were available from 13 individuals.
      RESULTS: TRIM5alphahu messenger RNA levels were lower in the PBMCs of HIV-1
      infected subjects than in those of uninfected subjects (P <.001). Seroconverters
      had lower preinfection levels of TRIM5alphahu than did nonseroconverters
      (P<.001). TRIM5alphahu levels did not change significantly after infection. There
      was no correlation between TRIM5alphahu levels and viral loads or CD4(+) T cell
      counts. CONCLUSIONS: High expression of TRIM5alphahu is associated with reduced
      susceptibility to HIV-1 infection. Furthermore, infection is not associated with
      disregulation of TRIM5alphahu. TRIM5alphahu expression levels do not contribute
      to the control of primary HIV-1 viremia.

PMID- 19388853
TI  - Becoming and growing--what does integration mean?

PMID- 19388852
TI  - Influence of hepatitis B virus (HBV) genotype on the clinical course of disease
      in patients coinfected with HBV and hepatitis delta virus.
AB  - OBJECTIVE: We evaluated the influence of hepatitis B virus (HBV) genotype on the
      course of disease in patients coinfected with HBV and hepatitis delta virus
      (HDV). METHODS: We evaluated HBV genotypes in 190 patients, 140 of whom had
      chronic HBV monoinfection and 50 of whom had chronic HBV-HDV coinfection. Real
      time polymerase chain reactions for the amplification of HBV DNA and HDV RNA were
      developed, and we compared the patient groups with respect to HBV genotype, viral
      load, alanine aminotransferase (ALT) and bilirubin levels, and disease severity.
      RESULTS: Coinfected patients had higher ALT and bilirubin levels as well as a
      higher prevalence of liver cirrhosis and liver carcinoma. ALT levels were higher
      among individuals coinfected with HDV and HBV genotype F than among individuals
      infected only with HBV genotype F. Among HDV-HBV-coinfected patients, HDV load
      was lower among those infected with HBV genotype A than among those infected with
      HBV genotype D or genotype F. CONCLUSION: Liver inflammation and HDV load are
      influenced by HBV genotype in individuals coinfected with HBV and HDV.

PMID- 19388854
TI  - Royal jelly increases high density lipoprotein levels but in older patients only.

PMID- 19388855
TI  - Development of an international questionnaire to measure use of complementary and
      alternative medicine (I-CAM-Q).
AB  - OBJECTIVES: Existing studies on the use of complementary and alternative medicine
      (CAM) have produced diverse results regarding the types and prevalence of CAM use
      due, in part, to variations in the measurement of CAM modalities. A questionnaire
      that can be adapted for use in a variety of populations will improve CAM
      utilization measurement. The purposes of this article are to (1) articulate the
      need for such a common questionnaire; (2) describe the process of questionnaire
      development; (3) present a model questionnaire with core questions; and (4)
      suggest standard techniques for adapting the questionnaire to different languages
      and populations. METHODS: An international workshop sponsored by the National
      Research Center in Complementary and Alternative Medicine (NAFKAM) of the
      University of Tromso, Norway, brought CAM researchers and practitioners together
      to design an international CAM questionnaire (I-CAM-Q). Existing questionnaires
      were critiqued, and working groups drafted content for a new questionnaire. A
      smaller working group completed, tested, and revised this self-administered
      questionnaire. RESULTS: The questionnaire that was developed contains four
      sections concerned with visits to health care providers, complementary treatments
      received from physicians, use of herbal medicine and dietary supplements, and
      self-help practices. A priori-specified practitioners, therapies, supplements,
      and practices are included, as well as places for researcher-specified and
      respondent-specified additions. Core questions are designed to elicit frequency
      of use, purpose (treatment of acute or chronic conditions, and health
      maintenance), and satisfaction. A penultimate version underwent pretesting with
      "think-aloud" techniques to identify problems related to meaning and format. The
      final questionnaire is presented, with suggestions for testing and translating.
      CONCLUSIONS: Once validated in English and non-English speaking populations, the
      I-CAM-Q will provide an opportunity for researchers to gather comparable data in
      studies conducted in different populations. Such data will increase knowledge
      about the epidemiology of CAM use and provide the foundation for evidence-based
      comparisons at an international level.

PMID- 19388856
TI  - Homeopathic practitioner's experiences of the homeopathic consultation: a
      protocol of a grounded theory study.
AB  - BACKGROUND: The apparent success of homeopathy is often attributed to a
      collaborative, holistic, and empathic consultation and to the practitioner
      patient relationship. Despite the practitioner's consultative style being shown
      to affect patient's health outcomes in conventional medicine, most research into
      the homeopathic consultation has focused on patients' experiences. However, the
      practitioner is a crucial component of the therapeutic context and may therefore
      have an important part to play in optimizing health outcomes in homeopathy.
      Additionally, the mechanisms underlying therapist effects are still poorly
      understood in clinical medicine generally and particularly so in homeopathy. AIM:
      The aim of this research is to gain an in-depth understanding of homeopathic
      practitioners' perceptions and experiences of the consultation, and the process
      of engaging with the patient and prescribing the remedy. We propose to generate a
      theoretical model to explain the processes that underpin the homeopathic
      consultation. DESIGN: This is a qualitative study using grounded theory
      methodology. Two (2) phases of data collection will be involved. Phase 1 will
      involve face-to-face in-depth interviews with homeopaths. From these interviews,
      a theoretical model of the homeopathic consultation will be developed. Phase 2 of
      data collection will involve observations of homeopathic consultations and the
      use of practitioner diaries in order to test the emerging theoretical model from
      phase 1. Homeopaths will be sampled from the Faculty of Homeopathy and the
      Society of Homeopaths. RESULTS: Results will be available in summer 2009.
      CONCLUSIONS: The findings from this study will lead to the development of a
      theoretical model of how homeopaths view and enact the consultation process.
      Revealing this process may influence the training of new practitioners and
      improve the practice of experienced practitioners and will therefore be of
      benefit to patients. In addition, the findings may be of potential benefit to
      practitioners of other therapeutic consultations.

PMID- 19388857
TI  - A review of the reliability of traditional East Asian medicine diagnoses.
AB  - BACKGROUND: In the practice of forms of traditional East Asian medicine (TEAM)
      such as Traditional Chinese Medicine and Japanese meridian therapy, treatment
      follows identification of underlying "patterns of disharmony." However, little is
      known in an objective sense of the consistency or reliability of diagnosis within
      TEAM. This is important: If diagnosis is not reliable, there can be less
      confidence that optimal treatment is received. TEAM systems have their own
      diagnostic endpoints that are used as evidence of change. If these are to be
      incorporated into clinical studies, a prerequisite is that they are reliable. Few
      studies have assessed the reliability of diagnostic data collected during a TEAM
      examination. The majority have investigated reliability of pulse diagnosis, with
      results ranging from low to a very good level of agreement. Studies of
      reliability of tongue diagnosis and other diagnostic data collected in a Chinese
      Medicine examination suggest considerable variability. In general, studies of
      reliability of pattern diagnosis and treatment in a range of disorders have not
      found a high level of reliability. A range of factors may affect reliability.
      OBJECTIVES: This paper reviews the current knowledge of reliability of TEAM
      diagnoses, including limitations of studies, and discusses the implications for
      practice and research and how to improve the current situation.

PMID- 19388858
TI  - Providing massage therapy for people with advanced cancer: what to expect.
AB  - There is very little information in the literature to prepare massage therapists
      for what they might expect when they provide treatment to people with advanced
      cancer in hospice or palliative care. We report an analysis of a subset of data
      collected from a large multi-site clinical trial of the efficacy of massage
      therapy for people with advanced cancer. This is the first analysis of empirical
      data of patient presentation, massage treatment environment, and the
      characteristics of massage provided for this population.

PMID- 19388859
TI  - Effects of therapeutic massage on the quality of life among patients with breast
      cancer during treatment.
AB  - OBJECTIVE: Therapeutic massage has demonstrated positive physical and emotional
      benefits to offset the effects of treatments associated with breast cancer. The
      goal of this study was to assess the impact of therapeutic massage on the quality
      of life of patients undergoing treatment for breast cancer. DESIGN: Using a
      pre/post intervention assessment design, this prospective, convenience sample
      pilot study measured anxiety, pain, nausea, sleep quality, and quality of life.
      Treatment consisted of one 30-minute treatment per week for 3 consecutive weeks.
      OUTCOME MEASURES: Instruments selected for this study were used in previous
      massage therapy studies to measure quality of life/health status and have
      documented validity and reliability. RESULTS: Participants experienced a
      reduction in several quality of life symptom concerns after only 3 weeks of
      massage therapy. Respondents' cumulative pre- and post-massage mean for state
      anxiety, sleep quality, and quality of life/functioning showed significant
      improvement. Among study participants, there was variability in reported episodes
      of nausea, vomiting, and retching; although participants reported decreased pain
      and distress, changes were non-significant. CONCLUSIONS: Therapeutic massage
      shows potential benefits for ameliorating the effects of breast cancer treatment
      by reducing side affects of chemotherapy and radiation and improving perceived
      quality of life and overall functioning.

PMID- 19388860
TI  - Reduction of conscious sedation requirements by olfactory stimulation: a
      prospective randomized single-blinded trial.
AB  - OBJECTIVES: This study investigated the possibility that olfactory stimulation
      would decrease sedation needed for colonoscopy and therefore decrease the
      recovery time needed after conscious sedation. MATERIALS AND METHODS: Patients
      were randomized to receive a cherry-flavoredscent in oxygen flowing at a 4 L per
      minute rate via nasal cannula or oxygen alone. The scent was provided in a cherry
      flavored oil. A Bispectral Index (BIS) monitor (Aspect Medical Systems, Newton,
      MA) was placed and scores were recorded every 5 minutes during the procedure to
      control for different sedation patterns between different endoscopists. The
      recovery area nurse was unaware of whether a given patient was in the aroma or
      plain oxygen group, and based each patient's discharge on preexisting
      standardized criteria. RESULTS: Two hundred and eighty-four (284) patients
      completed the study. Both the procedure times and the recovery times were not
      statistically significant between the two groups. The doses of sedatives used,
      BIS scores at 5 minute intervals, and rate of change in BIS scores were also not
      statistically significant between the two groups. CONCLUSIONS: Overall, there is
      no difference between olfactory stimulation and inhaled oxygen with regard to
      amount of sedation used and recovery times for colonoscopy. An inhaled cherry-
      scent may not have as great a calming effect as other scents that have been
      studied.

PMID- 19388861
TI  - Impact of acupuncture on vasomotor rhinitis: a randomized placebo-controlled
      pilot study.
AB  - OBJECTIVES: Chronic rhinitis without an allergic or infectious etiology
      (vasomotor rhinitis) is a common disease for which there are only few and not
      very effective therapeutic treatment options. The current placebo-controlled,
      partially double-blinded pilot study evaluated the effects of acupuncture on the
      symptoms of vasomotor rhinitis. DESIGN: A total of 24 patients with confirmed
      diagnosis of vasomotor rhinitis were randomly allocated to either acupuncture or
      sham laser acupuncture treatment. The sham laser was a deactivated laser pen
      beaming normal red light. The main outcome measure was the alteration of the
      nasal sickness score (NSS; score(max) 27 points). Secondary outcome measures were
      the evaluation of a subjective symptoms score by patients' diaries and of their
      quality of life (SF-12 health survey). A credibility assessment regarding the
      respective treatment was performed. The study is registered as an International
      Standard Randomised Controlled Trial, number NCT00682162. RESULTS: NSS of
      patients treated by acupuncture was significantly reduced from 9.3 +/- 3.89 to
      4.1 +/- 3.20 points (p < 0.001), whereas NSS declined from 5.6 +/- 2.74 to 3.7 +/
      2.61 points after sham treatment (p < 0.05). Comparison between the groups
      revealed a significant change of NSS (Mann-Whitney, p < 0.01), an analysis that
      also considers the significant difference between the baseline values of both
      groups (p < 0.05). Secondary outcome measures did not show significant
      differences between both groups. The credibility assessment was comparable for
      both treatments. CONCLUSIONS: This pilot study showed significant effects of
      acupuncture compared to a sham treatment in the NSS on symptoms of vasomotor
      rhinitis. These results may justify the performance of a large randomized trial
      to strengthen our understanding of the therapeutic value of acupuncture in the
      treatment of vasomotor rhinitis.

PMID- 19388862
TI  - A new nonpharmacological method in fibromyalgia: the use of wool.
AB  - OBJECTIVES: The aim was to assess the effect of wool use in patients with
      fibromyalgia. BACKGROUND: Various studies concerning the treatment of patients
      with fibromyalgia using nonpharmacological methods have been carried out. There
      are, however, no reports on the use of wool clothing and bedding in treating
      these patients. DESIGN AND METHODS: The study employed two-group, experimental
      design. A total of 50 patients with fibromyalgia, based on the criteria of the
      American College of Rheumatology, were selected for the study. They were
      distributed equally into two groups: a control group and a treatment group. The
      25 patients in each group were randomly selected and the compositions of the two
      groups were statistically identical. The patients in the treatment group wore
      woolen underwear (which covered the body from the shoulders to the thighs) and
      used woolen bedding such as woolen bed liner, woolen quilt and pillow during the
      experimental period of 6 weeks. All patients were assessed at the beginning the
      trial (pre-test) and the end of 6th (post-test) week. Data were collected using
      the visual analogue scale (0-10), tender points count, and Fibromyalgia Impact
      Questionnaire. RESULTS: Patients in the treatment group reported significant
      improvements in their conditions including a reduction in pain levels, tender
      point counts, and all scores of the Fibromyalgia Impact Questionnaire (p <or=
      0.001). CONCLUSIONS: The use of woolen underwear and woolen bedding were
      effective in reducing the symptoms of patients suffering from fibromyalgia. The
      use of wool is recommended as a means of treatment for alleviating the pain of
      fibromyalgia. RELEVANCE TO CLINICAL PRACTICE: Nurses provide professional support
      to patients with fibromyalgia. They select suitable clothes and sleeping
      materials for their patients with this object in mind: to keep their patients
      warm and to protect them from the cold.

PMID- 19388863
TI  - Associations between pet ownership and self-reported health status in people
      suffering from chronic fatigue syndrome.
AB  - OBJECTIVE: This study explored the association between pet ownership and self
      reported health in people suffering from chronic fatigue syndrome (CFS). METHODS:
      One hundred and ninety-three (193) people with medically diagnosed CFS completed
      a postal survey designed to collect information on illness severity, physical and
      psychologic health, and pet ownership practices. RESULTS: Most of the
      participants were female (72.0%), over 45 years of age (57.1%) and married
      (41.1%) with no children (63.1%). Pets were owned by 58.3% of the sample, with
      dogs and cats being the most commonly kept types of companion animal. The general
      health of the participants was discovered to be poor, as assessed by scores on
      the Chalder Fatigue Questionnaire (CFQ), General Health Questionnaire-12 (GHQ
      12), and Short-Form-36 (SF-36) health survey. Pet ownership was not significantly
      associated with scores on the CFQ, GHQ-12, or SF-36 scales, although pet owners
      considered their animals to offer them a range of health benefits, notably those
      associated with mental well-being. CONCLUSIONS: Overall, findings suggest no
      statistically significant association between pet ownership and self-reported
      health in people with CFS. Nonetheless, people suffering from this condition
      believe that their pets have the potential to enhance quality of life. Although
      animals should not be regarded as a panacea for people with long-term conditions
      such as CFS, they may, nonetheless, serve a valuable, and currently
      underutilized, role in promoting well-being, whether in their own right, or in
      conjunction with more traditional forms of therapy.

PMID- 19388864
TI  - The efficacy and tolerability of adjunctive alternative herbal medicine (Salvia
      miltiorrhiza and Pueraria lobata) on vascular function and structure in coronary
      patients.
AB  - BACKGROUND: Danshen and gegen (D&G) have long been used in treatment of angina
      and other cardiac symptoms in Chinese materia medica. Recent pharmacological
      studies suggest their therapeutic values. We aimed to evaluate the efficacy and
      safety of Salvia miltiorrhiza (danshen) and Pueraria lobata (gegen) in secondary
      prevention. METHODS: One hundred (100) consecutive coronary patients (mean age 58
      +/- 8 years) were randomized to adjunctive treatment with D&G combination (3 g)
      or placebo (6 capsules) for 24 weeks in double-blind parallel fashion, followed
      by optional open-label D&G (1.5 g/day) for 6 more months. Brachial flow-mediated
      dilation (FMD) and carotid intima-media thickness (IMT) were measured using
      ultrasound. RESULTS: Baseline characteristics were similar between the 2 groups.
      After 24 weeks and compared with baseline, there were no significant changes in
      blood pressures, blood hematological and biochemical profiles, or folate and
      homocysteine levels in both groups, but there was a mild decrease in low density
      lipoprotein (LDL) cholesterol in both groups (p < 0.05). Brachial FMD improved
      during D&G (p < 0.001) and less so during placebo treatment (p < 0.05), while
      improvement in carotid IMT was observed only in the D&G group (p < 0.05). After
      open-label D&G treatment for 6 more months (n = 45), further improvement in both
      brachial FMD (p < 0.0001) and carotid IMT (p < 0.0001) was observed. Eight (8)
      adverse events were reported-6 during placebo and 2 during D&G treatment
      requiring treatment termination in 2 patients (on placebo). CONCLUSIONS: D&G
      adjunctive treatment in coronary patients was well tolerated and effective in
      improving vascular function and structure. These two herbs may become a novel
      agent for secondary prevention.

PMID- 19388865
TI  - In vivo effects of Ashwagandha (Withania somnifera) extract on the activation of
      lymphocytes.
AB  - OBJECTIVE: This study investigated the immunologic effects of Ashwagandha
      (Withania somnifera) on four types of immune cells in a human sample to determine
      the immunologic mechanism. DESIGN: Five (5) participants consumed 6 mL of an
      Ashwagandha root extract twice daily for 96 hours. Ashwagandha was administered
      with anupana (whole milk). Peripheral blood samples were collected at 0, 24, and
      96 hours and compared for differences in cell surface expression of CD4, CD8,
      CD19, CD56, and CD69 receptors by flow cytometry. RESULTS: Significant increases
      were observed in the expression of CD4 on CD3+ T cells after 96 hours. CD56+ NK
      cells were also activated after 96 hours as evidenced by expression of the CD69
      receptor. At 96 hours of use, mean values of receptor expression for all measured
      receptor types were increased over baseline, indicating that a major change in
      immune cell activation occurred across the sample. CONCLUSIONS: Effects on immune
      cell activation with use of Ashwagandha warrant further study.

PMID- 19388866
TI  - Effectiveness of guarana (Paullinia cupana) for postradiation fatigue and
      depression: results of a pilot double-blind randomized study.
AB  - CONTEXT AND OBJECTIVE: Guarana (Paullinia cupana) has been used medicinally for
      centuries. The aim of this study is evaluate the effectiveness of guarana in the
      treatment of postradiation depression and fatigue. DESIGN AND SETTING: This study
      had a double-blind randomized design with crossover between experimental arms, at
      Faculdade de Medicina da Fundacao do ABC. METHODS: We conducted a randomized
      double-blind crossover trial with 36 patients with breast cancer undergoing
      adjuvant radiation therapy. We randomized patients to either guarana 75 mg daily
      p.o. or to placebo. Patients were switched to the other experimental arm at the
      middle of the radiation treatment, which consisted of 28 daily fractions of 180
      cGy. Evaluations were conducted at the beginning, at the middle, and at the end
      of radiation therapy. RESULTS: We were unable to show any statistically
      significant differences between the guarana and the placebo-treated group with
      any of the measured scores. Also, within the same group, we did not see any
      statistically significant associations during either the guarana- or placebo
      treated periods with any of the aforementioned measures. CONCLUSIONS: We were
      unable to show that patients with breast cancer undergoing radiation therapy
      derive any advantage with guarana over placebo for both fatigue and depressive
      symptoms.

PMID- 19388867
TI  - Is prayer CAM?
AB  - BACKGROUND: Alternative medicine researchers and policy makers have classified
      prayer as a mind-body intervention, and thus, a modality of complementary and
      alternative medicine (CAM). As such, numerous epidemiological surveys of CAM
      utilization-which have included prayer-depict increasing CAM use, particularly in
      specific racial and ethnic groups. OBJECTIVES: This paper discusses the
      implications of conflating prayer and CAM, especially regarding the definitions
      of both concepts and the resulting statistics of CAM utilization.

PMID- 19388869
TI  - Abstracts from the North American Research Conference on Complementary and
      Integrative Medicine. May 12-15, 2009. Minneapolis, Minnesota, USA.

PMID- 19388868
TI  - Shakuyaku-kanzo-to induces pseudoaldosteronism characterized by hypokalemia,
      rhabdomyolysis, metabolic alkalosis with respiratory compensation, and increased
      urinary cortisol levels.
AB  - BACKGROUND: Licorice, the primary ingredient of the Japanese herbal medicine
      shakuyaku-kanzo-to, can cause pseudoaldosteronism. Thus, shakuyaku-kanzo-to can
      cause this condition. CASE DESCRIPTION: A 79-year-old woman was brought to the
      emergency room. She had been experiencing general fatigue, numbness in the hands,
      and weakness in the lower limbs and could not stand up without assistance. She
      presented with hypokalemia (potassium level, 1.7 mEq/L), increased urinary
      excretion of potassium (fractional excretion of K, 21.2%), abnormalities on an
      electrocardiogram (flat T waves in II, III, AVF, and V1-6), rhabdomyolysis
      (creatine kinase level, 28,376 U/L), myopathy, metabolic alkalosis with
      respiratory compensation (O(2) flow rate, 2 L/min; pH, 7.473; pco(2), 61.0 mm Hg;
      po(2), 78.0 mm Hg; HCO(3), 44.1 mmol/L), hypertension (174/93 mm Hg),
      hyperglycemia (blood glucose level, 200-300 mg/dL), frequent urination,
      suppressed plasma renin activity (0.1 ng/mL/hour), decreased aldosterone levels
      (2.6 ng/dL), and increased urinary cortisol levels (600.6 microg/day; reference
      range, 26.0-187.0 microg/day). CONCLUSIONS: In this case, the observed reduction
      in the urinary cortisol levels, from 600.6 to 37.8 microg/day, led to a
      definitive diagnosis of pseudoaldosteronism instead of the apparent
      mineralocorticoid excess syndrome. Discontinuing shakuyaku-kanzo-to treatment and
      administering spironolactone and potassium proved effective in improving the
      patient's condition. Medical practitioners prescribing shakuyaku-kanzo-to should
      take into account the association between licorice, which is its main ingredient,
      and pseudoaldosteronism.

PMID- 19388871
TI  - Resources for infection prevention and control on the World Wide Web.
AB  - This review summarizes infection prevention resources on the Internet. Web sites
      are presented in 8 categories: guidelines, policies, and regulatory bodies;
      health care-associated infection and multidrug-resistant organisms; surveillance,
      reporting, and initiatives; antibiotic use; employee health; long-term care
      facilities; facility and environmental infection control; and professional
      societies, educational opportunities, and listserves. For example, links to the
      National Surgical Quality Improvement Program and National Healthcare Safety
      Network reports are provided among resources for infection surveillance,
      reporting, and initiatives. A link to guidelines for infection prevention in
      health care workers is listed with other information regarding employee health.
      The Web address for the Society for Healthcare Epidemiology of America guidelines
      for infection control in long-term care facilities is listed with resources for
      long-term care facilities. Guidelines for construction and environmental services
      are summarized with other information regarding facility and environmental
      infection control. This review summarizes the most useful and up-to-date
      infection prevention resources on the Internet and will simplify the search for
      pertinent information.

PMID- 19388872
TI  - Decreased risk of congenital cytomegalovirus infection in children born to HIV-1
      infected mothers in the era of highly active antiretroviral therapy.
AB  - BACKGROUND: We evaluated the prevalence of congenital cytomegalovirus (CMV)
      infection before and after highly active antiretroviral therapy (HAART)
      availability among neonates born to human immunodeficiency virus type 1 (HIV-1)
      infected mothers. We also identified maternal risk factors associated with in
      utero CMV transmission. METHOD: Routine screening for congenital CMV infection
      was performed from 1993 through 2004 in children born to HIV-1-infected mothers
      included in the French Perinatal Cohort (Enquete Perinatale Francaise).
      Interpretable tests on urine samples collected within the first 10 days of life
      were available for 4797 of the 7563 live-born infants. Prevalence was estimated
      for different time periods. Univariate and multivariate logistic regression
      analyses were performed to identify factors associated with CMV transmission in
      the HAART era. RESULTS: Among live-born children, the overall prevalence of CMV
      infection was 2.3% (95% confidence interval, 1.9%-2.8%). Prevalence was higher
      among HIV-1-infected neonates (10.3%; 95% confidence interval, 5.6%-17.0%) than
      among HIV-1-uninfected neonates (2.2%; 95% confidence interval, 1.8%-2.7%; P <
      .01). Among HIV-1-uninfected neonates, the prevalence of CMV infection decreased
      over time, from 3.5% in 1997-1998 to 1.2% in 2003-2004. Delivery period, maternal
      age, time at antiretroviral treatment initiation, and maternal CD4(+) cell count
      <200 cells/mm(3) close to delivery were independently associated with CMV
      infection in logistic regression analysis. The percentage of symptomatic CMV
      infections was 23.1% among HIV-1-infected newborns and 6.7% among HIV-1
      uninfected neonates. CONCLUSIONS: The prevalence of congenital CMV infection was
      high and associated with high morbidity rates among HIV-1-infected neonates.
      Conversely, the prevalence of CMV infection decreased over time among neonates
      not infected with HIV-1, reaching levels similar to those observed in the general
      population, following the introduction and increasing use of HAART for prevention
      of mother-to-child HIV-1 transmission.

PMID- 19388873
TI  - Synthesis and biological evaluation of novel hydrazide based cytotoxic agents.
AB  - Recently, we designed and synthesized a series of pyrroloquinoxaline compounds
      with hydrazine moiety linking a nitrogen-containing polycyclic group to a
      heteroaroyl system. Several derivatives, with attractive drug-like properties,
      were identified as promising cytotoxic agents, showing excellent potency in a
      panel of cancer cell lines. In the current study, we synthesized a further 19 new
      analogues to optimize their physicochemical properties and assess a coherent
      mechanism of action. Several chemical modifications were made to the reference
      compounds by varying the fused-ring system and/or the heteroacyl moiety. To
      evaluate their in vitro activity, we tested these compounds in six human cancer
      cell lines derived from different origins. Among them, two compounds ( 9 and 12 )
      showed similar potency as the reference compounds with IC(50) values in the sub
      micromolar range in all cell lines tested. Furthermore, compound 12 showed
      excellent in vivo efficacy in our preliminary human ovarian cancer mouse
      xenograft studies. Flow cytometric studies indicated that both derivatives
      interrupted cell cycle progression in colorectal cancer HCT116 cell lines and
      ovarian cancer SKOV-3 cells. Further mechanistic studies revealed that 9 and 12
      were able to induce reactive oxygen species in SKOV-3 cells with apparently
      different kinetic patterns. Considering their cytotoxicity profiles in a variety
      of in vitro and in vivo cancer models, these hydrazide based compounds seem to
      have considerable potentials as novel chemotherapeutics.

PMID- 19388874
TI  - Donepezil (aricept) as a treatment for anorexia nervosa: a very feasible
      therapeutic possibility.
AB  - Anorexia nervosa is a serious, multifactorial disease, characterized by
      psychiatric and neurological disturbances, which would appear to be similar to
      the manifestations of dementia. Patients with anorexia nervosa present
      compromised affectivity, characterized by hypomanic, manic and depressive
      symptoms, and their cholinergic system is altered with a decrease in the release
      of acetylcholine. Donepezil is a drug that been proven to be effective in the
      treatment of dementia, including Alzheimer's; it has been used for affective
      disorders and its mechanism of action is to inhibit the acetylcholinesterase
      enzyme to increase acetylcholine. Therefore, donepezil could be effective in
      treating anorexia nervosa.

PMID- 19388875
TI  - Putting the 'HAT' back on survival signalling: the promises and challenges of
      HDAC inhibition in the treatment of neurological conditions.
AB  - Decreased histone acetyltransferase activity and transcriptional dysfunction have
      been implicated in almost all neurodegenerative conditions. Increasing net
      histone acetyltransferase activity through inhibition of the histone deacetylases
      (HDACs) has been shown to be an effective strategy to delay or halt progression
      of neurological disease in cellular and rodent models. These findings have
      provided firm rationale for Phase I and Phase II clinical trials of HDAC
      inhibitors in Huntington's disease, spinal muscular atrophy, and Freidreich's
      ataxia. In this review, we discuss the current findings and promise of HDAC
      inhibition as a strategy for treating neurological disorders. Despite the fact
      that HDAC inhibitors are in an advanced stage of development, we suggest other
      approaches to modulating HDAC function that may be less toxic and more
      efficacious than the canonical agents developed so far.

PMID- 19388877
TI  - Investigational drugs for neuroendocrine tumours.
AB  - BACKGROUND: Neuroendocrine tumours (NETs) are usually slow-growing neoplasms,
      which arise in the gastrointestinal tract, endocrine pancreas, lungs or thymus.
      The majority are malignant. The treatment of patients with metastatic disease
      consists of biotherapy with alpha-interferon and somatostatin analogues, various
      chemotherapy combinations or liver embolization. OBJECTIVE: To review and discuss
      new treatments for patients with metastatic NETs. METHOD: Review of the published
      literature during the last 5 years on treatment of patients with NETs.
      RESULTS/CONCLUSION: Several new drugs with various mechanisms of action including
      cytotoxic drugs, tyrosine kinase receptor inhibitors and antiangiogenic drugs as
      well as radiolabelled substances have been introduced during recent years. Many
      of these compounds have shown promising results in patients with NETs.

PMID- 19388878
TI  - Recent developments in the treatment of uveitis: an update.
AB  - The management of complex uveitis is often based around the use of oral
      corticosteroids. To spare the side effects of corticosteroids, second-line oral
      immunosuppressant drugs are used. Newer systemic immunosuppressive drugs,
      including biologics, and locally delivered treatments are being evaluated. This
      article reviews current conventional treatments, discusses their limitations and
      evaluates newer treatment strategies. Current theories about the pathogenesis of
      uveitis and potential targets for treatment are discussed in this context. We are
      still in search of a low-risk, where possible, locally delivered and targeted
      treatment for uveitis.

PMID- 19388876
TI  - Cathepsin K inhibitors for osteoporosis and potential off-target effects.
AB  - Cathepsin K is a highly potent collagenase and the predominant papain-like
      cysteine protease expressed in osteoclasts. Cathepsin K deficiencies in humans
      and mice have underlined the central role of this protease in bone resorption
      and, thus, have rendered the enzyme as an attractive target for anti-resorptive
      osteoporosis therapy. In the past decade, a lot of efforts have been made in
      developing highly potent, selective and orally applicable cathepsin K inhibitors.
      Some of these inhibitors have passed preclinical studies and are presently in
      clinical trials at different stages of advancement. The development of the
      inhibitors and preliminary results of the clinical trials revealed problems and
      lessons concerning the in situ specificity of the compounds and their tissue
      targeting. In this review, we briefly summarize the history of cathepsin K
      research and discuss the current development of cathepsin K inhibitors as novel
      anti-resorptives for the treatment of osteoporosis. We also discuss potential off
      target effects of cathepsin K inhibition and alternative applications of
      cathepsin K inhibitors in arthritis, atherosclerosis, blood pressure regulation,
      obesity and cancer.

PMID- 19388879
TI  - Transcatheter arterial chemoembolization combined with or without Chinese herbal
      therapy for hepatocellular carcinoma: meta-analysis.
AB  - OBJECTIVE: Chinese herbal therapy is sometimes used in conjunction with
      transcatheter arterial chemoembolization (TACE) for the treatment of
      hepatocellular carcinoma (HCC) in Asian countries. This study aims to
      systemically review the efficacy of Chinese herbal therapy in HCC patients
      receiving TACE. METHODS: Meta-analysis was performed for clinical trials
      comparing Chinese herbal therapy versus no Chinese herbal therapy given to HCC
      patients receiving TACE. Publications in 10 electronic databases were extensively
      searched. RESULTS/CONCLUSION: Chinese herbal therapy was associated with a
      significant rise in the number of patients with survival > 1-year, 2-year and 3
      year, as well as a significant rise in the number of patients who reported
      complete or partial response and non-deterioration performance status. Chinese
      herbal therapy also showed significant efficacies in the increase of T cells and
      natural killer cells, whereas a significant lower blood alpha-fetoprotein
      concentration was reported. There were a significant increase in white blood cell
      count, a significant lower risk in patients with nausea and vomiting, and a
      significant rise in patients with increased body weight when Chinese herbal
      therapy was given. The evidence from this review supports the use of Chinese
      herbal therapy to enhance the efficacy of TACE in HCC patients. However, owing to
      limited data and heterogeneity of the included studies, further trials are
      required.

PMID- 19388880
TI  - VEGF inhibitors for the treatment of neovascular age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      Western world for those patients aged 50 years or older. Neovascular AMD, a
      subtype characterized by the growth of new, pathologic blood vessels, results in
      most of the cases of severe and rapid vision loss associated with AMD. A critical
      activator of angiogenesis in neovascular AMD is VEGF. Several therapies have been
      and are now being developed for neovascular AMD, with the goal of inhibiting
      VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full
      length antibodies ranibizumab and bevacizumab, VEGF receptor decoy VEGF Trap,
      small interfering RNA-based therapies bevasiranib and AGN211745, sirolimus, and
      tyrosine kinase inhibitors including vatalanib, pazopanib, TG100801, TG101095,
      AG013958 and AL39324. At present, established therapies have met with great
      success in reducing the vision loss associated with neovascular AMD, whereas
      those still investigational in nature offer the potential for further advances.

PMID- 19388881
TI  - Pharmacological approaches to the treatment of obstructive sleep apnoea.
AB  - BACKGROUND: Currently the treatment of choice for symptomatic obstructive sleep
      apnoea (OSA) is continuous positive airway pressure (CPAP). Some patients with
      OSA do not tolerate CPAP or have insufficiently severe symptoms to justify its
      use; for these patients, drug therapy would be a desirable potential therapeutic
      alternative. OBJECTIVE: To summarize the current evidence on the effectiveness of
      drug therapy in patients with OSA. METHODS: A systematic review of randomized
      controlled trials was performed to investigate the effects of drug therapy on
      OSA. RESULTS/CONCLUSIONS: Searches of bibliographical databases revealed 33
      trials investigating the effects of 27 different drugs on OSA severity and/or
      symptoms. The mechanisms by which these drugs are supposed to improve OSA
      include, amongst others, an increase in tone of the upper airways, an increase in
      ventilatory drive, a reduction in airway resistance, and alterations in surface
      tension forces in the upper airway. In most of these studies there was no
      significant effect on OSA observed. However, there is evidence from a few small
      trials that some drugs, especially those thought to increase upper airway muscle
      tone, have the potential to reduce OSA severity; but further data from larger
      studies of adequate duration are needed.

PMID- 19388882
TI  - Cancer vaccination with telomerase peptide GV1001.
AB  - Telomerase is highly expressed in essentially all cancer forms, while the
      expression in normal tissues is restricted. Moreover, telomerase activity is
      considered indispensable for tumor immortalization and growth. Human telomerase
      reverse transcriptase (hTERT), the rate-limiting subunit of the telomerase
      complex, is therefore an attractive target for cancer vaccination. The present
      review provides an update on the development of GV1001, a peptide vaccine
      representing a 16-aa hTERT sequence. GV1001 binds multiple HLA class II molecules
      and harbors putative HLA class I epitopes. The peptide may therefore elicit
      combined CD4/CD8 T-cell responses, considered important to initiate tumor
      eradication and long-term memory. Phase I/II trials in advanced pancreatic and
      pulmonary cancer patients have demonstrated GV1001-specific T-cell responses in >
      50% of subjects, without clinically important toxicity. The results indicate a
      correlation between development of GV1001-specific responses and prolonged
      survival. However, as in most cancer vaccine trials, a large proportion of immune
      responders experience no clinical benefit. Long-term survivors harbor durable
      GV1001-specific T-cell responses with high IFN-gamma/IL-10 ratios and
      polyfunctional cytokine patterns. Interestingly, the cytokine profiles do not
      follow a T(H)1/T(H)2 delineation. Here, the author discusses how immunomonitoring
      may be improved to discriminate between efficient and pointless immune responses,
      and which questions to address in the further development of GV1001.

PMID- 19388883
TI  - Limb-specific and cross-transfer effects of arm-crank exercise training in
      patients with symptomatic peripheral arterial disease.
AB  - Arm cranking is a useful alternative exercise modality for improving walking
      performance in patients with intermittent claudication; however, the mechanisms
      of such an improvement are poorly understood. The main aim of the present study
      was to investigate the effects of arm-crank exercise training on lower-limb O2
      delivery in patients with intermittent claudication. A total of 57 patients with
      intermittent claudication (age, 70+/-8 years; mean+/-S.D.) were randomized to an
      arm-crank exercise group or a non-exercise control group. The exercise group
      trained twice weekly for 12 weeks. At baseline and 12 weeks, patients completed
      incremental tests to maximum exercise tolerance on both an arm-crank ergometer
      and a treadmill. Respiratory variables were measured breath-by-breath to
      determine peak VO2 (O2 uptake) and ventilatory threshold. Near-IR spectroscopy
      was used in the treadmill test to determine changes in calf muscle StO2 (tissue
      O2 saturation). Patients also completed a square-wave treadmill-walking protocol
      to determine VO2 kinetics. A total of 51 patients completed the study. In the
      exercise group, higher maximum walking distances (from 496+/-250 to 661+/-324 m)
      and peak VO2 values (from 17.2+/-2.7 to 18.2+/-3.4 ml.kg-1 of body mass.min-1)
      were recorded in the incremental treadmill test (P<0.05). After training, there
      was also an increase in time to minimum StO2 (from 268+/-305 s to 410+/-366 s), a
      speeding of VO2 kinetics (from 44.7+/-10.4 to 41.3+/-14.4 s) and an increase in
      submaximal StO2 during treadmill walking (P<0.05). There were no significant
      changes in the control group. The results suggest that the improvement in walking
      performance after arm-crank exercise training in patients with intermittent
      claudication is attributable, at least in part, to improved lower-limb O2
      delivery.

PMID- 19388884
TI  - The combined neuroprotective effects of lidocaine and dexmedetomidine after
      transient forebrain ischemia in rats.
AB  - BACKGROUND: We investigated whether coadministration of lidocaine and
      dexmedetomidine would reduce brain injury following transient forebrain ischemia
      in rats to a greater extent than either drug alone. METHODS: Adult male Sprague
      Dawley rats were anesthetized with halothane to maintain normocapnia and
      normoxia. Rats received subcutaneous injection of saline 1 ml/kg, lidocaine 10
      mg/kg, dexmedetomidine 3 microg/kg, or lidocaine 10 mg/kg plus dexmedetomidine 3
      microg/kg. Thirty minutes after the drug injection, forebrain ischemia was
      induced by hemorrhagic hypotension and occlusion of the bilateral carotid
      arteries, and was confirmed by isoelectric EEG. At the end of 10-min ischemia,
      rats were reperfused. The same dose of drugs was administered 3, 24, and 48 h
      after ischemia. Neurological examination was done at 1, 2, and 7 days after
      ischemia. Seven days after ischemia, the brain was stained with hematoxylin and
      eosin. We counted ischemic cells in the CA1 hippocampal region, striatum, and
      cerebral cortex. We also measured extracellular glutamate and norepinephrine
      concentration in hippocampal CA1 in the four groups. RESULTS: As compared with
      saline-treated rats, rats receiving dexmedetomidine plus lidocaine showed less
      than neurological deficit scores at 2 and 7 days after ischemia, and had less
      ischemic cells in the CA1 region. However, administration of dexmedetomidine plus
      lidocaine did not alter the area under the glutamate concentration curve and
      norepinephrine concentration during ischemia in the CA1 region, compared with
      saline-treated rats. CONCLUSIONS: Our results suggest coadministration of
      lidocaine and dexmedetomidine improves the neurological outcome without
      alteration of glutamate and norepinephrine concentrations during forebrain
      ischemia in rats.

PMID- 19388885
TI  - The three-way stopcock may be a weak component of total intravenous anaesthesia.
AB  - BACKGROUND: An intravenous line is needed to administer anaesthesia, particularly
      when total intravenous anaesthesia (TIVA) is performed. A disadvantage of TIVA is
      that the intravenous concentration of anaesthetics cannot be easily measured
      compared with volatile anaesthetics. If a three-way stopcock is accidentally
      unscrewed, TIVA drugs cannot reach the patient's veins, thus resulting in
      inadequate anaesthesia levels, possibly resulting in awareness. We therefore
      measured the required torque to open five different brands of three-way stopcocks
      in an attempt to make an intravenous-line including all elements safer. METHODS:
      The torque required to open one, two or three three-way stopcocks being connected
      in a perpendicular manner was measured with a biaxial servo hydraulic material
      testing machine. RESULTS: The force required to open three-way stopcocks
      connected with an intravenous catheter ranged in five different stopcock models
      from 5.03+/-0.75 to 2.21+/-0.51 N respectively; with two three-way stopcocks from
      2.68+/-0.42 to 1.31+/-0.59 N, respectively, and with three three-way stopcocks
      from 1.29+/-0.27 to 0.82+/-0.05 N, respectively. CONCLUSION: Turning a three-way
      stopcock to become loose with possibly leaking drugs requires minimal amounts of
      force and decreases significantly if not connected in-line.

PMID- 19388886
TI  - Continuous femoral nerve block after total knee arthroplasty?
AB  - BACKGROUND: A continuous femoral nerve block is frequently used as an adjunct
      therapy after total knee arthroplasty (TKA). However, there is still debate on
      its benefits. METHODS: In this prospective, randomized study, patients received a
      basic analgesic regimen of paracetamol and dicloflenac for the first 48 h
      postoperatively. In addition, the study group received a continuous femoral nerve
      block. A morphine patient-controlled analgesia pump was also available as a
      rescue analgesic to all the patients. Patients' numeric rating scores for pain,
      the amount of morphine consumed and its side effects during the first 48 h were
      recorded. Knee flexion angles achieved during the first week were registered.
      Three months postoperatively, patients completed Western Ontario and McMaster
      Universities Osteoarthritis Index and Knee Society Score. RESULTS: The study
      group (n=27) had less pain (P=0.0016) during the first 48 h, was more satisfied
      with the analgesia (P<0.001) and used less morphine (P=0.007) compared with the
      control group (n=26). Fewer patients were nauseated, vomited or were drowsy in
      the study group (P=0.001). Also, the study group achieved better knee flexion in
      the first 6 days after surgery (P=0.001), with more patients reaching 90 degrees
      flexion than the control group. However, after 3 months, there were no
      significant functional differences between the groups. CONCLUSION: A continuous
      femoral nerve block leads to better analgesia, less morphine consumption and less
      morphine-related side effects after TKA. Early functional recovery is improved,
      resulting in more patients reaching 90 degrees knee flexion after 6 days.
      However, after 3 months, no significant functional benefits were found.

PMID- 19388887
TI  - Endotoxin-like reaction following once-daily gentamicin.
AB  - An endotoxin-like reaction is a host response to an agent that induces the
      release of endogenous pyrogens, including cytokines. The typical reaction that is
      associated with gentamicin is fever and chills, rigor, shivering, tachycardia
      with hypertension or hypotension, respiratory symptoms and muscle cramps. We
      report a case of a 92-year-old patient who developed an endotoxin-like reaction
      in the post-operative recovery unit following 200 mg of gentamicin. The reported
      side effect is not included in the drug sheet or in the British National
      Formulary. No similar incidents were reported in the UK. We discuss the clinical
      picture of this rare event, along with a review of the literature and
      recommendations.

PMID- 19388888
TI  - A Scandinavian survey of drug administration through inhalation, suctioning and
      recruitment maneuvers in mechanically ventilated patients.
AB  - BACKGROUND: The aim was to describe current practices for drug administration
      through inhalation, endotracheal suctioning and lung recruitment maneuvers in
      mechanically ventilated patients in Scandinavian intensive care units (ICUs).
      METHODS: We invited 161 ICUs to participate in a web-based survey regarding (1)
      their routine standards and (2) current treatment of ventilated patients during
      the past 24 h. In order to characterize the patients, the lowest PaO(2) with the
      corresponding highest FiO(2), and the highest PaO(2) with the corresponding
      lowest FiO(2) during the 24-h study period were recorded. RESULTS: Eighty-seven
      ICUs answered and reported 186 patients. Positive end-expiratory pressure (PEEP)
      levels (cmH(2)O) were 5-9 in 65% and >10 in 31% of the patients. Forty percent of
      the patients had heated humidification and 50% received inhalation of drugs.
      Endotracheal suctioning was performed >7 times during the study period in 40% of
      the patients, of which 23% had closed suction systems. Twenty percent of the
      patients underwent recruitment maneuvers. The most common recruitment maneuver
      was to increase PEEP and gradually increase the inspiratory pressure. Twenty-six
      percent of the calculated PaO(2)/FiO(2) ratios varied >13 kPa for the same
      patient. CONCLUSION: Frequent use of drug administration through inhalation and
      endotracheal suctioning predispose to derecruitment of the lungs, possibly
      resulting in the large variations in PaO(2)/FiO(2) ratios observed during the 24
      h study period. Recruitment maneuvers were performed only in one-fifth of the
      patients during the day of the survey.

PMID- 19388889
TI  - Effects of sevoflurane on cognitive deficit, motor function, and histopathology
      after cerebral ischemia in rats.
AB  - BACKGROUND: The volatile anesthetic sevoflurane exhibits neuroprotective
      properties when assessed for motor function and histopathology after cerebral
      ischemia in rats. Damage of hippocampal neurons after ischemia relates to a
      number of cognitive deficits that are not revealed by testing animals for motor
      function. Therefore, the present study evaluates cognitive and behavioral
      function as well as hippocampal damage in rats subjected to cerebral ischemia
      under sevoflurane compared with fentanyl/nitrous oxide (N(2)O)/O(2) anesthesia.
      METHODS: Thirty-four rats were trained for 10 days using a hole-board test to
      detect changes in cognitive and behavioral function. Rats were randomly assigned
      to the following groups: (A) sham/fentanyl/N(2)O/O(2) (n=7); (B)
      ischemia/fentanyl/N(2)O/O(2) (n=10); (C) sham/2.0 vol% sevoflurane in O(2)/air
      (n=7); and (D) ischemia/2.0 vol% sevoflurane in O(2)/air (n=10). Cerebral
      ischemia was produced by unilateral common carotid artery occlusion combined with
      hemorrhagic hypotension (mean arterial blood pressure 40 mmHg for 45 min).
      Temperature, arterial blood gases, and pH were maintained constant. Cerebral
      blood flow was measured using laser-Doppler flowmetry. After surgery, cognitive
      and behavioral function was re-evaluated for 10 days. On day 11, the brains were
      removed for histopathologic evaluation (hematoxylin/eosin-staining). RESULTS:
      Cognitive testing revealed deficits in declarative and working memory in ischemic
      rats anesthetized with fentanyl/N(2)O. Rats anesthetized with sevoflurane during
      ischemia showed a significantly better outcome. Hippocampal damage was
      significantly worse with fentanyl/N(2)O. CONCLUSION: The present data add to
      previous investigations showing that sevoflurane prevents a deficit in cognitive
      function and histopathological damage induced by cerebral ischemia in rats.

PMID- 19388890
TI  - Referral and treatment patterns for complex regional pain syndrome in the
      Netherlands.
AB  - BACKGROUND: Patients with complex regional pain syndrome (CRPS) are seen and
      treated by a variety of physicians. The present study aims to describe referral
      and treatment patterns for CRPS patients in the Netherlands. METHODS: Patients,
      who were selected (1996-2005) from an electronic general practice (GP) database
      (Integrated Primary Care Information Project), were invited for study
      participation, involving diagnosis verification (International Association for
      the Study of Pain criteria) and assessment of referrals and treatment through
      information retrieved from GP journals, patients' questionnaires, pharmacy
      dispensing lists and specialist letters if available. RESULTS: One hundred and
      two patients were included. Sixty-one percent had presented first at the GP,
      while 80% subsequently consulted one or more medical specialists, most frequently
      an anesthetist (55% of the cases) or a specialist in rehabilitation medicine
      (41%). Over 90% of the patients received oral or topical pharmacotherapy, 45%
      received intravenous therapy, 89% received non-invasive therapy (i.e.
      physiotherapy) and 18% received nerve blocks. Analgesics and free radical
      scavengers were administered early during CRPS, while vasodilating drugs and
      drugs against neuropathic pain (antidepressants and anti-epileptics) were
      administered later on. Pharmacotherapy was usually initiated by a medical
      specialist. CONCLUSION: The Dutch treatment guidelines, issued in 2006, recommend
      free radical scavenger prescription (plus physiotherapy) as the initial treatment
      step for CRPS. Until 2005 only half of the patients received a scavenger within 3
      months after disease onset, and the majority presents first at the GP, in
      particular GPs may be encouraged to initiate treatment with scavengers, while
      waiting for the results of further specialist consultation.

PMID- 19388891
TI  - Long-term physical outcome in patients with septic shock.
AB  - BACKGROUND: Limited information is available on physical function after septic
      shock. The aim of the present study was to assess the physical outcome in
      survivors 1 year after septic shock. METHODS: The outcome status of all 174 adult
      patients admitted to a mixed ICU with the diagnosis septic shock in a 1-year
      period was registered. Survivors were interviewed about physical function and
      socioeconomic status using a questionnaire including the Short Form-36 survey.
      The pre-ICU-admission Functional Comorbidity Index (FCI) was also registered.
      RESULTS: Of the 80 survivors, two were still hospitalised; thus, 78 were invited
      to participate and 70 replied (inclusion-rate 88%). Patients were followed up at
      median 351 days after hospital discharge. At follow-up the patients had a
      markedly reduced physical component summary score (PCS) compared with age- and
      sex-adjusted general population controls (36 vs. 47, P<0.0001). This was also
      observed in patients with no comorbidity before ICU admission (34 vs. 47,
      P<0.001). There was a negative correlation (r=-0.27, P=0.03) between pre-ICU
      admission FCI values and the PCS at follow-up. According to 81% of the patients,
      loss of muscle mass was the main cause of decreased physical function. Only 43%
      (10 vs. 23, P=0.01) of the previously employed had returned to work, and the
      number of patients in need of home-based personal assistance had doubled (10/20,
      P=0.04). CONCLUSION: Physical function is substantially reduced in survivors of
      septic shock 1 year after discharge.

PMID- 19388892
TI  - Predictors of cardiac events in high-risk patients undergoing emergency surgery.
AB  - BACKGROUND: The aim of this study was to determine the incidence of myocardial
      damage and left ventricular myocardial dysfunction and their influence on outcome
      in high-risk patients undergoing non-elective surgery. METHODS: In this
      prospective observational study, 211 patients with American Society of
      Anesthesiologists classification III or IV undergoing emergent or urgent surgery
      were included. Troponin I (TnI) was measured pre-operatively, 12 and 48 h post
      operatively. Pre-operative N-terminal fragment of B-type natriuretic peptide (NT
      proBNP), as a marker for left ventricular systolic dysfunction, was analyzed. The
      diagnostic thresholds were set to TnI >0.06 microg/l and NT-proBNP >1800 pg/ml,
      respectively. Post-operative major adverse cardiac events (MACE), 30-day and 3
      months mortality were recorded. RESULTS: Elevated TnI levels were detected in 33%
      of the patients post-operatively. A TnI elevation increased the risk of MACE (35%
      vs. 3% in patients with normal TnI levels, P<0.001) and 30-day mortality (23% vs.
      7%, P=0.003). Increased concentrations of NT-proBNP were seen in 59% of the
      patients. Elevated NT-proBNP was an independent predictor of myocardial damage
      post-operatively, odds ratio, 6.2 [95% confidence interval (CI) 2.1-18.0] and
      resulted in an increased risk of MACE (21% vs. 2.5% in patients with NT-proBNP <
      or = 1800 pg/ml, P<0.001). CONCLUSION: Myocardial damage is common in a high-risk
      population undergoing unscheduled surgery. These results suggest a close
      correlation between myocardial damage in the post-operative period and increased
      concentration of NT-proBNP before surgery. The combinations of TnI and NT-proBNP
      are reliable markers for monitoring patients at risk in the peri-operative period
      as well as useful tools in our risk assessment pre-operatively in emergency
      surgery.

PMID- 19388893
TI  - Relaxing music as pre-medication before surgery: a randomised controlled trial.
AB  - INTRODUCTION: Patients who await surgery often suffer from fear and anxiety,
      which can be prevented by anxiolytic drugs. Relaxing music may be an alternative
      treatment with fewer adverse effects. This randomised clinical trial compared pre
      operative midazolam with relaxing music. METHOD: Three hundred and seventy-two
      patients scheduled for elective surgery were randomised to receive pre-operative
      prevention of anxiety by 0.05-0.1 mg/kg of midazolam orally or by relaxing music.
      The main outcome measure was the State Trait Anxiety Inventory (STAI X-1), which
      was completed by the patients just before and after the intervention. RESULTS: Of
      the 177 patients who completed the music protocol, the mean and (standard
      deviation) STAI-state anxiety scores were 34 (8) before and 30 (7) after the
      intervention. The corresponding scores for the 150 patients in the midazolam
      group were 36 (8) before and 34 (7) after the intervention. The decline in the
      STAI-state anxiety score was significantly greater in the music group compared
      with the midazolam group (P<0.001, 95% confidence interval range -3.8 to -1.8).
      CONCLUSION: Relaxing music decreases the level of anxiety in a pre-operative
      setting to a greater extent than orally administrated midazolam. Higher
      effectiveness and absence of apparent adverse effects makes pre-operative
      relaxing music a useful alternative to midazolam for pre-medication.

PMID- 19388894
TI  - Quality of cardiopulmonary resuscitation on manikins: on the floor and in the
      bed.
AB  - BACKGROUND: In general, in-hospital resuscitation is performed in a bed and out
      of-hospital resuscitation on the floor. The surface under the patient may affect
      the cardiopulmonary resuscitation (CPR) quality; therefore, we evaluated CPR
      quality (the percentage of chest compressions of correct depth) and rescuer's
      fatigue (the mean compression depth minute by minute) when CPR is performed on a
      manikin on the floor or in the bed. METHODS: Forty-four simulated cardiac arrest
      scenarios of 10 min were treated by intensive care unit (ICU) nurses in pairs
      using a 30 : 2 chest compression-to-ventilation ratio. The rescuer who performed
      the compressions was changed every 2 min. CPR was randomly performed either on
      the floor or in the bed without a backboard; in both settings, participants
      kneeled beside the manikin. RESULTS: A total number of 1060 chest compressions,
      44% with correct depth, were performed on the floor; 1068 chest compressions were
      performed in the bed, and 58% of these were the correct depth. These differences
      were not significant between groups. The mean compression depth during the
      scenario was 44.9+/-6.2 mm (mean+/-SD) on the floor and 43.0+/-5.9 mm in the bed
      (P=0.3). The mean chest compression depth decreased over time on both surfaces
      (P<0.001), indicating rescuer fatigue, but this change was not different between
      the groups (P=0.305). CONCLUSIONS: ICU nurses perform chest compression as
      effectively on the floor as in the bed. The mean chest compression depth
      decreases over time, but the surface had no significant effect.

PMID- 19388895
TI  - Mortality in diabetic patients undergoing non-cardiac surgery: a 7-year follow-up
      study.
AB  - BACKGROUND: The prognosis of diabetic patients after non-cardiac surgery remains
      controversial. This study was designed to compare the long-term mortality between
      diabetic and non-diabetic control patients undergoing non-cardiac surgery and to
      evaluate the possible risk factors. METHODS: We investigated 274 consecutive
      diabetic patients and 282 non-diabetic control patients who underwent non-cardiac
      surgery within 1 year in a tertiary care hospital in Finland. The control group
      was matched for the same type of operations. Patients were followed for up to 7
      years on average. The main outcome measure was mortality within 7 years. RESULTS:
      Mortality both in the short-term postoperatively (< or =21 days) and in the long
      term (up to 87 (1/2) months) was significantly higher in the diabetic patients
      compared with the non-diabetic group: 3.5 vs. 0% (P<0.05) and 37.2 vs. 15%
      (P<0.00001), respectively. The major causes of death among diabetic subjects were
      diseases of the cardiovascular system (56.8%) compared with non-diabetic patients
      (18.6%), P<0.0001. We found that diabetes mellitus per se is not a risk factor
      for post-operative mortality but a combination of variables had a significant
      effect on both short- and long-term mortality. CONCLUSION: Diabetic patients
      undergoing non-cardiac surgery had a significantly higher incidence of short-term
      post-operative and long-term mortality compared with non-diabetic subjects. We
      propose a model of predictors of death among diabetic individuals undergoing non
      cardiac surgery within a 7-year follow-up. The majority of deaths were associated
      with cardiovascular diseases.

PMID- 19388896
TI  - Isoflurane attenuates pulmonary interleukin-1beta and systemic tumor necrosis
      factor-alpha following mechanical ventilation in healthy mice.
AB  - BACKGROUND: Mechanical ventilation (MV) induces an inflammatory response in
      healthy lungs. The resulting pro-inflammatory state is a risk factor for
      ventilator-induced lung injury and peripheral organ dysfunction. Isoflurane is
      known to have protective immunological effects on different organ systems. We
      tested the hypothesis that the MV-induced inflammatory response in healthy lungs
      is reduced by isoflurane. METHODS: Healthy C57BL6 mice (n=34) were mechanically
      ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cmH(2)O;
      and fraction of inspired oxygen, 0.4) for 4 h under general anesthesia using a
      mix of ketamine, medetomidine and atropine (KMA). Animals were divided into four
      groups: (1) Unventilated control group; (2) MV group using KMA anesthesia; (3) MV
      group using KMA with 0.25 MAC isoflurane; (4) MV group using KMA with 0.75 MAC
      isoflurane. Cytokine levels were measured in lung homogenate and plasma.
      Leukocytes were counted in lung tissue. RESULTS: Lung homogenates: MV increased
      pro-inflammatory cytokines. In mice receiving KMA+ isoflurane 0.75 MAC, no
      significant increase in interleukin (IL)-1beta was found compared with non
      ventilated control mice. PLASMA: MV induced a systemic pro-inflammatory response.
      In mice anesthetized with KMA+ isoflurane (both 0.25 and 0.75 MAC), no
      significant increase in tumor necrosis factor (TNF)-alpha was found compared with
      non-ventilated control mice. CONCLUSIONS: The present study is the first to show
      that isoflurane attenuates the pulmonary IL-1beta and systemic TNF-alpha response
      following MV in healthy mice.

PMID- 19388897
TI  - Isoflurane enhances spontaneous Ca(2+) oscillations in developing rat hippocampal
      neurons in vitro.
AB  - BACKGROUND: During the nervous system development, spontaneous synchronized
      Ca(2+) oscillations are thought to possess integrative properties because their
      amplitude and frequency can influence the patterning of neuronal connection,
      neuronal differentiation, axon outgrowth, and long-distance wiring. Accumulating
      studies have confirmed that some drugs such as volatile anesthetic isoflurane
      produced histopathologic changes in the central nervous system in juvenile animal
      models. Because the hippocampus plays an important role in learning and memory,
      the present work was designed to characterize the Ca(2+) oscillations regulated
      by volatile anesthetic isoflurane in primary cultures of developing hippocampal
      neurons (5-day-cultured). METHODS: Primary cultures of rat hippocampal neurons (5
      day-cultured) were loaded with the Ca(2+) indicator Fluo-4AM (4 microM) and were
      studied with a confocal laser microscope. RESULTS: Approximately 22% of 5-day
      cultured hippocampal neurons exhibited typical Ca(2+) oscillations. These
      oscillations were dose-dependently enhanced by isoflurane (EC50 0.5 MAC, minimum
      alveolar concentration) and this effect could be reverted by bicuculline (50
      microM), a specific gamma-aminobutyric acid (GABA(A)) receptor antagonist.
      CONCLUSION: Unlike its depressant effect on the Ca(2+) oscillations in adult
      neurons in previous researches, isoflurane dose-dependently enhanced calcium
      oscillations in developing hippocampal neurons by activating GABA(A) receptors, a
      major excitatory receptor in synergy with N-methyl-d-aspartate receptors at the
      early stages of development. It may be involved in the mechanism of an isoflurane
      induced neurotoxic effect in the developing rodent brain.

PMID- 19388898
TI  - The Danish version of the questionnaire on pain communication: preliminary
      validation in cancer patients.
AB  - BACKGROUND: The modified version of the patients' Perceived Involvement in Care
      Scale (M-PICS) is a tool designed to assess cancer patients' perceptions of
      patient-health care provider pain communication process. The objective of this
      study was to examine the psychometric properties of the shortened Danish version
      of the M-PICS (SDM-PICS). METHODS: The validated English version of the M-PICS
      was translated into Danish following the repeated back-translation procedure.
      Cancer patients were recruited for the study from specialized pain management
      facilities. RESULTS: Thirty-three patients responded to the SDM-PICS, Danish
      Barriers Questionnaire II, Hospital Anxiety and Depression Scale, and Brief Pain
      Inventory Pain Severity Scale. A factor analysis of the SDM-PICS resulted in two
      factors: Factor one, patient information, consisted of four items assessing the
      extent to which the patient shared information with his/her health care provider,
      and Factor two, health care provider information, consisted of four items
      measuring the degree to which a health care provider was perceived as the one who
      shares information. Two separate items addressed the perceived level of
      information exchange between the patient and the health care provider. The SDM
      PICS total had an internal consistency of 0.88. The SDM-PICS scores were
      positively related to pain relief and inversely related to the measures of
      cognitive pain management barriers, anxiety, and reported pain levels.
      CONCLUSION: The SDM-PICS seems to be a reliable and valid measure of perceived
      patient-health care provider communication in the context of cancer pain.

PMID- 19388899
TI  - Unilateral spinal anaesthesia for outpatient surgery: a comparison between
      hyperbaric bupivacaine and bupivacaine-clonidine combination.
AB  - BACKGROUND: Low-dose hyperbaric bupivacaine has been used to produce unilateral
      spinal anaesthesia for outpatient surgery. Unilateral spinal anaesthesia is
      associated with reduction of hypotension, faster recovery and increased patient
      satisfaction. Small doses of clonidine have shown effectiveness in intensifying
      spinal anaesthesia. We investigated the effect of adding 15 microg of clonidine
      to 5 mg hyperbaric bupivacaine on unilaterality. METHODS: Sixty patients
      undergoing outpatient knee arthroscopy were randomly allocated to receive either
      1.2 ml (6 mg) of hyperbaric bupivacaine or a 1.2 ml solution containing 1.0 ml (5
      mg) hyperbaric bupivacaine, 0.1 ml (75 microg) clonidine and 0.1 ml sterile
      water. The motor block was assessed by a modified Bromage scale and the sensory
      block by a pinprick. RESULTS: There was a significant difference in the spread of
      anaesthesia between the operated and contralateral sides in both groups. Seventy
      seven per cent of the blocks were unilateral in group B and 73% in group B-C.
      There was no significant difference between the groups, in unilaterality. The
      motor block was prolonged in group B-C but it did not affect home-readiness.
      Patients receiving clonidine needed more vasopressors. There was a significant
      difference in blood pressures between the groups, being lower in group B-C after
      1 h 45 min. CONCLUSION: Using 5 mg hyperbaric bupivacaine with 15 microg of
      clonidine, the unilaterality can be achieved and spinal anaesthesia intensified
      without affecting home-readiness. More vasopressors are needed in the beginning,
      but after the surgery patients experienced less pain.

PMID- 19388900
TI  - Perineural meperidine blocks nerve conduction in a dose-related manner: a
      randomized double-blind study.
AB  - BACKGROUND: Meperidine has been shown to exhibit a sensory block in peripheral
      nerves. However, its motor blockade ability is controversial. The aim of this
      study was to investigate, electroneurographically, the ability of meperidine to
      inhibit conduction in both sensory and motor fibres in the ulnar nerve. MATERIALS
      AND METHODS: The study was conducted in a double-blind, placebo-controlled
      fashion. Eighteen healthy volunteers were randomized into three groups (Saline,
      meperidine 1% and meperidine 2%). Three millilitre of the study solution was
      administered to the ulnar nerve perineurally at the level of the wrist by the
      guidance of a nerve stimulator. Sensory nerve action potential (SNAP) and
      compound motor action potential (CMAP) amplitudes were recorded. At least a 20%
      decrease in the initial response amplitude was accepted as a block. RESULTS: The
      number of individuals with sensory and motor block with saline, meperidine 1% and
      meperidine 2% were 0/6, 6/6, 6/6 and 0/6, 5/6, 6/6, respectively (P<0.05). The
      maximum decrease in the median SNAP and CMAP amplitude values were 4.7% and 8.3%
      with saline; 38.5% and 46.4% with meperidine 1%; and 100% and 97.8% with
      meperidine 2%, respectively (P<0.05). Median values for the duration of sensory
      and motor block with meperidine 1% and meperidine 2% were 45, 52.5 and 30, 32.5
      min, respectively. CONCLUSION: Meperidine blocks sensory and motor nerve
      conduction in a dose-related manner.

PMID- 19388901
TI  - Signs of critical illness polyneuropathy and myopathy can be seen early in the
      ICU course.
AB  - BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is recognized as
      a common condition that develops in the intensive care unit (ICU). It may lead to
      a prolonged hospital stay with subsequent increased ICU and hospital costs.
      Knowledge of predisposing factors is insufficient and the temporal pattern of
      CIPNM has not been well described earlier. This study investigated patients with
      critical illness in need of prolonged mechanical ventilation, describing
      comprehensively the time course of changes in muscle and nerve neurophysiology,
      histology and mitochondrial oxidative function. METHODS: Ten intensive care
      patients were investigated 4, 14 and 28 days after the start of mechanical
      ventilation. Laboratory tests, neurophysiological examination, muscle biopsies
      and clinical examinations were performed. Neurophysiological criteria for CIPNM
      were noted and measurements for mitochondrial content, mitochondrial respiratory
      enzymes and markers of oxidative stress were performed. RESULTS: While all
      patients showed pathologic changes in neurophysiologic measurements, only
      patients with sepsis and steroid treatment (5/5) fulfilled the CIPNM criteria.
      The presence of CIPNM did not affect the outcome, and the temporal pattern of
      CIPNM was not uniform. All CIP changes occurred early in ICU care, while myopathy
      changes appeared somewhat later. Citrate synthase was decreased between days 4
      and 14, and mitochondrial superoxide dismutase was increased. CONCLUSION: With
      comprehensive examination over time, signs of CIPNM can be seen early in ICU
      course, and appear more likely to occur in patients with sepsis and
      corticosteroid treatment.

PMID- 19388902
TI  - Vaccinia-induced epidermal growth factor receptor-MEK signalling and the anti
      apoptotic protein F1L synergize to suppress cell death during infection.
AB  - F1L is a functional Bcl-2 homologue that inhibits apoptosis at the mitochondria
      during vaccinia infection. However, the extent and timing of cell death during
      DeltaF1L virus infection suggest that additional viral effectors cooperate with
      F1L to limit apoptosis. Here we report that vaccinia growth factor (VGF), a
      secreted virulence factor, promotes cell survival independently of its role in
      virus multiplication. Analysis of single and double knockout viruses reveals that
      VGF acts synergistically with F1L to protect against cell death during infection.
      Cell survival in the absence of F1L is dependent on VGF activation of the
      epidermal growth factor receptor. Furthermore, signalling through MEK kinases is
      necessary and sufficient for VGF-dependent survival. We conclude that VGF
      stimulates an epidermal growth factor receptor-MEK-dependent pro-survival pathway
      that synergizes with F1L to counteract an infection-induced apoptotic pathway
      that predominantly involves the BH3-only protein Bad.

PMID- 19388903
TI  - Scavenger receptors: role in innate immunity and microbial pathogenesis.
AB  - Accumulating evidence shows that many scavenger receptors (SR), including SR-A,
      MARCO and CD36, represent an important part of the innate immune defence by
      acting as pattern-recognition receptors, in particular against bacterial
      pathogens. Several SR are expressed on macrophages and dendritic cells, where
      they act as phagocytic receptors mediating non-opsonic phagocytosis of pathogenic
      microbes. Another important function of some SR is to act as co-receptors to Toll
      like receptors (TLR), modulating the inflammatory response to TLR agonists. On
      bacteria, the SR ligands have commonly been reported to be lipopolysaccharide and
      lipoteichoic acid, but recent advances in the field indicate that bacterial
      surface proteins play a more important role as target molecules for SR than
      previously thought. Interestingly, recent data show that major pathogens,
      including Streptococcus pyogenes and the group B streptococcus, have evolved
      mechanisms to evade SR-mediated recognition. Moreover, intracellular pathogens,
      such as hepatitis C virus and Plasmodium falciparum, utilize the SR to gain entry
      into host cells, focusing interest on the importance of SR also in the molecular
      pathogenesis of infectious diseases. This review highlights the complex
      interactions between SR and pathogenic microbes, and discusses the role of these
      interactions in host defence and microbial pathogenesis.

PMID- 19388905
TI  - Hypoxia: a window into Mycobacterium tuberculosis latency.
AB  - Tuberculosis is a massive public health problem on a global scale and the success
      of Mycobacterium tuberculosis is linked to its ability to persist within humans
      for long periods without causing any overt disease symptoms. Hypoxia is predicted
      to be a key host-induced stress limiting growth of the pathogen in vivo. However,
      multiple studies in vitro and in vivo indicate that M. tuberculosis adapts to
      oxygen limitation by entering into a metabolically altered state, while awaiting
      the opportunity to reactivate. Molecular signatures of bacteria adapted to
      hypoxia in vitro are accumulating, although correlations to human disease are
      only now being established. Similarly, defining the mechanisms that control this
      adaptation is an active area of research. In this review we discuss the
      historical precedents linking hypoxia and latency, and the gathering knowledge of
      M. tuberculosis hypoxic responses. We also examine the role of these responses in
      tuberculosis latency, and identify promising avenues for future studies.

PMID- 19388904
TI  - Intracellular biology and virulence determinants of Francisella tularensis
      revealed by transcriptional profiling inside macrophages.
AB  - Summary The highly infectious bacterium Francisella tularensis is a facultative
      intracellular pathogen, whose virulence requires proliferation inside host cells,
      including macrophages. Here we have performed a global transcriptional profiling
      of the highly virulent F. tularensis ssp. tularensis Schu S4 strain during its
      intracellular cycle within primary murine macrophages, to characterize its
      intracellular biology and identify pathogenic determinants based on their
      intracellular expression profiles. Phagocytosed bacteria rapidly responded to
      their intracellular environment and subsequently altered their transcriptional
      profile. Differential gene expression profiles were revealed that correlated with
      specific intracellular locale of the bacteria. Upregulation of general and
      oxidative stress response genes was a hallmark of the early phagosomal and late
      endosomal stages, while induction of transport and metabolic genes characterized
      the cytosolic replication stage. Expression of the Francisella Pathogenicity
      Island (FPI) genes, which are required for intracellular proliferation, increased
      during the intracellular cycle. Similarly, 27 chromosomal loci encoding putative
      hypothetical, secreted, outer membrane proteins or transcriptional regulators
      were identified as upregulated. Among these, deletion of FTT0383, FTT0369c or
      FTT1676 abolished the ability of Schu S4 to survive or proliferate
      intracellularly and cause lethality in mice, therefore identifying novel
      determinants of Francisella virulence from their intracellular expression
      profile.

PMID- 19388906
TI  - Host responses to a versatile commensal: PAMPs and PRRs interplay leading to
      tolerance or infection by Candida albicans.
AB  - The molecular interactions between commensal microorganisms and their host are
      basically different from those triggered by pathogens since they involve
      tolerance. When the commensal is genetically equipped to become an opportunistic
      pathogen, as is the case with Candida albicans, the picture becomes more complex.
      In this case, the balance between protection and invasion depends on host
      reactivity to altered microbial expression of ligands interacting with innate
      immune sensors. Based on experimental evidence obtained with C. albicans, we
      discuss the different molecular processes involved in the sensing of this
      important opportunistic human pathogen by a panel of pattern recognition
      receptors (PRRs) according to the numerous pathogen-associated molecular patterns
      (PAMPs) that can be exposed at its surface. Beneficial or deleterious immune
      responses that either maintain a commensal state or favour damage by the yeast
      result from this dynamic interplay.

PMID- 19388907
TI  - Mycobacterium requires an all-around closely apposing phagosome membrane to
      maintain the maturation block and this apposition is re-established when it
      rescues itself from phagolysosomes.
AB  - Pathogenic mycobacteria survive in macrophages of the host organism by residing
      in phagosomes which they prevent from undergoing maturation and fusion with
      lysosomes. Several molecular mechanisms have been associated with the phagosome
      maturation block. Here we show for Mycobacterium avium in mouse bone marrow
      derived macrophages that the maturation block required an all-around close
      apposition between the mycobacterial surface and the phagosome membrane. When
      small (0.1 microm) latex beads were covalently attached to the mycobacterial
      surface to act as a spacer that interfered with a close apposition, phagosomes
      rapidly acquired lysosomal characteristics as indicators for maturation and
      fusion with lysosomes. As a result, several mycobacteria were delivered into
      single phagolysosomes. Detailed electron-microscope observations of phagosome
      morphology over a 7-day post-infection period showed a linear correlation between
      bead attachment and phagosome-lysosome fusion. After about 3 days post infection,
      conditions inside phagolysosomes caused a gradual release of beads. This allowed
      mycobacteria to re-establish a close apposition with the surrounding membrane and
      sequester themselves into individual, non-maturing phagosomes which had lost
      lysosomal characteristics. By rescuing themselves from phagolysosomes,
      mycobacteria remained fully viable and able to multiply at the normal rate. In
      order to unify the present observations and previously reported mechanisms for
      the maturation block, we discuss evidence that they may act synergistically to
      interfere with 'Phagosome Membrane Economics' by causing relative changes in
      incoming and outgoing endocytic membrane fluxes.

PMID- 19388908
TI  - The emergence of combinatorial strategies in the development of RNA oncolytic
      virus therapies.
AB  - Oncolytic viruses (OVs) represent an exciting new biological approach to cancer
      therapy. In particular, RNA viruses have emerged as potent agents for oncolytic
      virotherapy because of their capacity to specifically target and destroy tumour
      cells while sparing normal cells and tissues. Several barriers remain in the
      development of OV therapy, including poor penetration into the tumour mass,
      inefficient virus replication in primary cancers, and tumour-specific resistance
      to OV-mediated killing. The combination of OVs with cytotoxic agents, such as
      small molecule inhibitors of signalling or immunomodulators, as well as stealth
      delivery of therapeutic viruses have shown promise as novel experimental
      strategies to overcome resistance to viral oncolysis. These agents complement OV
      therapy by unblocking host pathways, delivering viruses with greater efficiency
      and/or increasing virus proliferation at the tumour site. In this review, we
      summarize recent development of these concepts, the potential obstacles, and
      future prospects for the clinical utilization of RNA OVs in cancer therapy.

PMID- 19388909
TI  - The incremental benefit of a shortness-of-breath biomarker panel in emergency
      department patients with dyspnea.
AB  - OBJECTIVES: The objective was to determine the incremental benefit of a shortness
      of-breath (SOB) point-of-care biomarker panel on the diagnostic accuracy of
      emergency department (ED) patients presenting with dyspnea. METHODS: Adult ED
      patients at 10 U.S. EDs with SOB were included. The physician's estimates of the
      pretest clinical probability of heart failure (HF), acute myocardial infarction
      (MI), and pulmonary embolism (PE) were recorded using deciles (0%-100%). Blood
      samples were analyzed using a SOB point-of-care biomarker panel (troponin I,
      myoglobin, creatinine kinase-myocardial band isoenzyme [CK-MB], D-dimer, and B
      type natriuretic peptide [BNP]). Thirty-day follow-up for MI, HF, and PE was
      performed. Data were analyzed using logistic regression and receiver operating
      characteristics (ROC) curve analysis. RESULTS: Of 301 patients, the mean (+/
      standard deviation [SD]) age was 61 (+/-18) years; 56% were female, 58% were
      white, and 38% were African American. Diagnoses included MI (n = 54), HF (n =
      91), and PE (n = 16) in a total of 129 (43%) of the patients. High pretest
      clinical certainty (>or=80%) identified 60 of these 129 (46.5%) cases. The SOB
      point-of-care biomarker panel identified 66 additional cases of MI (n = 24), HF
      (n = 31), and PE (n = 11). The overall adjusted sensitivity for any diagnosis was
      increased from 65% to 70% with the addition of the SOB point-of-care biomarker
      panel (difference = 5%, 95% CI = -1.1% to 11%) while specificity was increased
      from 82% to 83% (difference = 1%, 95% CI = -4% to 7%). The model containing
      pretest probability and the results of the SOB panel had an area under the curve
      (AUC) of 83.4% (95% CI = 78.4% to 88.5%), which was not significantly better than
      the AUC of 80.4% (95% CI = 75.1% to 85.7%) for clinical probability alone.
      CONCLUSIONS: The addition of the SOB panel of markers did not improve the AUC for
      diagnosing the combined set of clinical conditions. Using the disease-specific
      SOB biomarkers increased the sensitivity on a disease-by-disease basis; however,
      specificity was reduced.

PMID- 19388910
TI  - An improvised oxygen supply system for pandemic and disaster use.
AB  - BACKGROUND: Current disaster planning for pandemic influenza anticipates
      overwhelming numbers of patients in need of hospitalization. The anticipated use
      of extra, or "surge," beds is common in both hospital and community disaster
      response planning. In a pandemic of respiratory illness, supplemental oxygen will
      be a life-saving intervention. There are currently few options to provide these
      proposed surge beds with the necessary oxygen. OBJECTIVES: A method of providing
      an improvised oxygen delivery system for use in a disaster was developed and
      tested. This system was designed to use readily available commercial materials to
      assemble an oxygen delivery system. METHODS: The study consisted of a laboratory
      design, assembly, and testing of an improvised oxygen system. RESULTS: A liquid
      oxygen (LOX) Dewar container was used to supply oxygen systems built from
      inexpensive commercially available plastic tubing and fittings. The system will
      drive ventilators without significant pressure drop or ventilator malfunction.
      The final developed system will supply 30 patients with up to 6 L/min (l pm)
      oxygen each by nasal cannula from a single oxygen Dewar. CONCLUSIONS: An
      improvised system to deliver oxygen for patient beds or ventilator use can be
      easily assembled in the event of a disaster. This could be life-saving in the
      event of a pandemic of respiratory illness.

PMID- 19388911
TI  - Time-dependent variations in ischemia-modified albumin levels in mesenteric
      ischemia.
AB  - OBJECTIVES: The objective was to determine the value of ischemia-modified albumin
      (IMA) in the diagnosis of mesenteric embolism. The authors investigated whether
      or not plasma IMA levels rose in the acute period in a rat model of mesenteric
      ischemia and the related time-dependent changes. METHODS: In this randomized,
      controlled, nonblinded trial, 36 mature female Wistar rats were divided into six
      groups: three control (Groups I, III, and V) and three ischemia (Groups II, IV,
      and VI). In the control groups, blood was sampled at 30 minutes (Group I), 2
      hours (Group III), and 6 hours (Group V) following a simple laparotomy. In the
      ischemia groups, following laparotomy, the superior mesenteric artery (SMA) was
      clamped using a bulldog clamp, and blood samples were taken at 30 minutes (Group
      II), 2 hours (Group IV), and 6 hours (Group VI). RESULTS: Plasma IMA levels in
      the ischemia groups were significantly higher compared to those of the control
      groups (p < 0.004). In addition, levels were higher in the 6-hour blood samples
      of the ischemia group than in the 2-hour and 30-minute samples (p < 0.001). Serum
      IMA was also higher in the 2-hour blood samples of the ischemia group than in the
      30-minute samples (p < 0.001). CONCLUSIONS: These preliminary findings suggest
      that serum IMA levels may represent a significant parameter in the early
      diagnosis of acute mesenteric ischemia and that further studies are necessary.

PMID- 19388912
TI  - Emergency medicine residency applicant perceptions of unethical recruiting
      practices and illegal questioning in the match.
AB  - OBJECTIVES: The authors hypothesized that unethical recruiting practices and
      illegal questioning occur during emergency medicine (EM) resident recruitment.
      The objectives were to estimate the prevalence of specific unethical recruiting
      practices and illegal questioning by EM programs based on the perceptions of
      residency applicants and to measure the effect of these perceptions on applicant
      appraisal of programs. METHODS: This was a cross-sectional survey of all
      applicants who matched to U.S. EM programs in 2005 and 2006. The survey
      questionnaire was developed by the study authors and was validated by pretesting
      on a small group representative of the study population. The survey addressed
      specific questions regarding program recruiting behaviors and interview
      questioning. The hyperlink to the secure anonymous online survey questionnaire
      was distributed to all EM program directors, asking them in turn to forward the
      hyperlink to their newly matched incoming residency class. All data were
      calculated with Score method with continuity correction and reported in
      proportions with 95% confidence intervals (CIs). RESULTS: The authors received
      671 survey responses. Among respondents, 56 (8.3%, 95% CI = 6.4% to 10.7%) stated
      that they were specifically asked to disclose at least one program's position on
      their rank list by a program representative, and 44 (6.6%, 95% CI = 4.9% to 8.9%)
      reported that they matched at a program residing lower on their rank list than at
      least one other program that had informed the applicant they were ranked to
      match. Furthermore, 201 respondents (30.0%, 95% CI = 26.5% to 33.7%) believed
      that they were asked at least one illegal question during their interviews, the
      most common of which was inquiry into their marital status (189 respondents:
      28.2%, 95% CI = 24.8% to 31.9%). Respondents were 11 times more likely to move a
      program to a lower position of preference on their rank order list (12.2%, 95% CI
      = 9.8% to 15.0%) rather than a higher position (1.1%, 95% CI = 0.5% to 2.3%) as a
      result of perceiving unethical recruiting behaviors or illegal questioning.
      CONCLUSIONS: These results demonstrate that among survey respondents, some
      perceived unethical recruiting behaviors and illegal questioning in the 2005 and
      2006 Match. Perceptions of such behaviors appeared to have a negative impact on
      applicant appraisal of EM residency programs.

PMID- 19388913
TI  - Redefining emergency medicine.

PMID- 19388914
TI  - Prescriptions for schedule II opioids and benzodiazepines increase after the
      introduction of computer-generated prescriptions.
AB  - BACKGROUND: Prescriptions for controlled substances decrease when regulatory
      barriers are put in place. The converse has not been studied. OBJECTIVES: The
      objective was to determine whether a less complicated prescription writing
      process is associated with a change in the prescribing patterns of controlled
      substances in the emergency department (ED). METHODS: The authors conducted a
      retrospective nonconcurrent cohort study of all patients seen in an adult ED
      between April 19, 2005, and April 18, 2007, who were discharged with a
      prescription. Prior to April 19, 2006, a specialized prescription form stored in
      a locked cabinet was obtained from the nursing staff to write a prescription for
      benzodiazepines or Schedule II opioids. After April 19, 2006, New York State
      mandated that all prescriptions, regardless of schedule classification, be
      generated on a specialized bar-coded prescription form. The main outcome of the
      study was to compare the proportion of Schedule III-V opioids to Schedule II
      opioids and benzodiazepines prescribed in the ED before and after the
      introduction of a less cumbersome prescription writing process. RESULTS: Of the
      26,638 charts reviewed, 2.1% of the total number of prescriptions generated were
      for a Schedule II controlled opioid before the new system was implemented
      compared to 13.6% after (odds ratio [OR] = 7.3, 95% confidence interval [CI] =
      6.4 to 8.4). The corresponding percentages for Schedule III-V opioids were 29.9%
      to 18.1% (OR = 0.52, 95% CI = 0.49 to 0.55) and for benzodiazepines 1.4% to 3.9%
      (OR = 2.8, 95% CI = 2.4 to 3.4). CONCLUSIONS: Patients were more likely to
      receive a prescription for a Schedule II opioid or a benzodiazepine after a more
      streamlined computer-generated prescription writing process was introduced in
      this ED.

PMID- 19388915
TI  - Routine packing of simple cutaneous abscesses is painful and probably
      unnecessary.
AB  - OBJECTIVES: The objective was to determine whether the routine packing of simple
      cutaneous abscesses after incision and drainage (I&D) confers any benefit over
      I&D alone. METHODS: In a prospective, randomized, single-blinded trial, subjects
      with simple cutaneous abscesses (less than 5 cm largest diameter) underwent
      incision, drainage, irrigation, and standard abscess preparation in the usual
      manner. Subjects were then randomized to either packing or no-packing. Visual
      analog scales (VAS; 100 mm) of pain were recorded in the emergency department
      (ED). All patients received trimethoprim-sulfamethoxazole (TMP-SMX), ibuprofen,
      and narcotic prescriptions, recorded twice daily VAS pain scores, and returned in
      48 hours at which time dressings and packing, if present, were removed and a
      physician blinded to the randomization and not part of the initial visit repeated
      measurements and determined the need for further intervention. RESULTS: Forty
      eight subjects were included in the final analysis. There were no significant
      differences in age, sex, abscess location, or initial pain scores between the two
      groups. There was no significant difference in need for a second intervention at
      the 48-hour follow-up between the packed (4 of 23 subjects) and nonpacked (5 of
      25 subjects) groups (p = 0.72; relative risk = 1.3, 95% confidence interval [CI]
      = 0.4 to 4.2). Patients in the group that received packing reported higher pain
      scores immediately postprocedure (mean difference = 23.8 mm; p = 0.014, 95% CI =
      5 to 42 mm) and at 48 hours postprocedure (mean difference = 16.4 mm; p = 0.03,
      95% CI = 1.6 to 31.2 mm), as well as greater use of ibuprofen (mean difference =
      0.32; p = 0.12, 95% CI = -1.4 to 2.0) and oxycodone/acetaminophen (mean
      difference = 2.19; p = 0.03, 95% CI = 0.2 to 4.1). CONCLUSION: In this pilot
      study, not packing simple cutaneous abscesses did not result in any increased
      morbidity, and patients reported less pain and used fewer pain medications than
      packed patients.

PMID- 19388917
TI  - Emergency department echocardiogram of right ventricle thrombus and McConnell's
      sign in a patient with dyspnea.

PMID- 19388918
TI  - Clinicopathological conference: a case of a 26-year-old male with diarrhea,
      weakness, and dizziness.

PMID- 19388919
TI  - Distances to emergency department and to primary care provider's office affect
      emergency department use in children.
AB  - OBJECTIVES: Patients of all ages use emergency departments (EDs) for primary
      care. Several studies have evaluated patient and system characteristics that
      influence pediatric ED use. However, the issue of proximity as a predictor of ED
      use has not been well studied. The authors sought to determine whether ED use by
      pediatric Medicaid enrollees was associated with the distance to their primary
      care providers (PCPs), distance to the nearest ED, and distance to the nearest
      children's hospital. METHODS: This historical cohort study included 26,038
      children age 18 and under, assigned to 332 primary care practices affiliated with
      a Medicaid health maintenance organization (HMO). Predictor variables were
      distance from the child's home to his or her PCP site, distance from home to the
      nearest ED, and distance from home to the nearest children's hospital. The
      outcome variable was each child's ED use. A negative binomial model was used to
      determine the association between distance variables and ED use, adjusted for
      age, sex, and race, plus medical and primary care site characteristics previously
      found to influence ED use. Distance variables were divided into quartiles to test
      for nonlinear associations. RESULTS: On average, children made 0.31 ED
      visits/person/year. In the multivariable model, children living greater than 1.19
      miles from the nearest ED had 11% lower ED use than those living within 0.5 miles
      of the nearest ED (risk ratio [RR] = 0.89, 95% CI = 0.81 to 0.99). Children
      living between 1.54 and 3.13 miles from their PCPs had 13% greater ED use (RR =
      1.13, 95% CI = 1.03 to 1.24) than those who lived within 0.7 miles of their PCP.
      CONCLUSIONS: Geographical variables play a significant role in ED utilization in
      children, confirming the importance of system-level determinants of ED use and
      creating the opportunity for interventions to reduce geographical barriers to
      primary care.

PMID- 19388920
TI  - Development and validation of the Excess Mortality Ratio-adjusted Injury Severity
      Score Using the International Classification of Diseases 10th Edition.
AB  - OBJECTIVES: This study aimed to develop and validate a new method for measuring
      injury severity, the excess mortality ratio-adjusted Injury Severity Score (EMR
      ISS), using the International Classification of Diseases 10th Edition (ICD-10).
      METHODS: An injury severity grade similar to the Abbreviated Injury Scale (AIS)
      was converted from the ICD-10 codes on the basis of quintiles of the EMR for each
      ICD-10 code. Like the New Injury Severity Score (NISS), the EMR-ISS was
      calculated from three maximum severity grades using data from the Korean National
      Injury Database. The EMR-ISS was then validated using the Hosmer-Lemeshow
      goodness-of-fit chi-square (HL chi-square, with lower values preferable), the
      area under the receiver operating characteristic curve (AUC-ROC), and the Pearson
      correlation coefficient to compare it with the International Classification of
      Diseases 9th Edition-based Injury Severity Score (ICISS). Nationwide hospital
      discharge abstract data (DAD) from stratified-sample general hospitals (n = 150)
      in 2004 were used for an external validation. RESULTS: The total number of study
      subjects was 29,282,531, with five subgroups of particular interest identified
      for further study: traumatic brain injury (TBI, n = 3,768,670), traumatic chest
      injury (TCI,n = 1,169,828), poisoning (n = 251,565), burns (n = 869,020), and DAD
      (n = 26,374). The HL chi-square was lower for EMR-ISS than for ICISS in all
      groups: 42,410.8 versus 55,721.9 in total injury, 7,139.6 versus 20,653.9 in TBI,
      6,603.3 versus 4,531.8 in TCI, 2,741.2 versus 9,112.0 in poisoning, 764.4 versus
      4,532.1 in burns, and 28.1 versus 49.4 in DAD. The AUC-ROC for death was greater
      for EMR-ISS than for ICISS: 0.920 versus 0.728 in total injury, 0.907 versus
      0.898 in TBI, 0.675 versus 0.799 in TCI, 0.857 versus 0.900 in poisoning, 0.735
      versus 0.682 in burns, and 0.850 versus 0.876 in DAD. The Pearson correlation
      coefficient between the two scores was )0.68 in total injury, )0.76 in TBI, )0.86
      in TCI, )0.69 in poisoning,)0.58 in burns, and )0.75 in DAD. CONCLUSIONS: The EMR
      ISS showed better calibration and discrimination power for prediction of death
      than the ICISS in most injury groups. The EMR-ISS appears to be a feasible tool
      for passive injury surveillance of large data sets, such as insurance data sets
      or community injury registries containing diagnosis codes. Additional further
      studies for external validation on prospectively collected data sets should be
      considered.

PMID- 19388922
TI  - Reliability of the color analog scale: repeatability of scores in traumatic and
      nontraumatic injuries.
AB  - OBJECTIVES: The objective was to assess in a pediatric emergency department (ED)
      the reliability of the color analog scale (CAS) for acute pain assessment,
      overall and between traumatic and nontraumatic pain etiology. METHODS: This was a
      prospective study of children aged 5 to 16 years in the ED of a children's
      hospital who had a complaint of pain. The CAS was administered to the patient at
      admission and at 30 minutes. To evaluate repeatability, a second measurement was
      obtained 1 minute following each assessment. This assumed there would be no
      substantial change in pain intensity within 1 minute. The authors used the
      intraclass correlation coefficient (ICC) to evaluate the repeatability of 1
      minute interval measurements. RESULTS: A total of 170 patients were enrolled. The
      origin of pain was traumatic in 81 cases (48%). Regardless of pain etiology, the
      CAS scores were highly repeatable (r = 0.97, 95% confidence interval [CI] = 0.95
      to 0.98). CONCLUSIONS: The color analog scale is both a valid and a reliable self
      reporting tool in the assessment of acute pain in children.

PMID- 19388923
TI  - A randomized, double-blind controlled study of jet lidocaine compared to jet
      placebo for pain relief in children undergoing needle insertion in the emergency
      department.
AB  - OBJECTIVES: The objectives were to determine whether pretreatment with needleless
      jet-delivered lidocaine decreases self-reported pain in children undergoing
      needle insertion in the emergency department (ED) and to explore whether
      pretreatment with a jet device decreases self-reported pain in children
      undergoing needle insertion in the ED. METHODS: This study examined needle
      insertion pain in children 5-18 years of age. In the first phase of this study,
      children received either pretreatment with jet-delivered lidocaine (0.2 mL of
      buffered 1% lidocaine; n = 75) or pretreatment with jet-delivered placebo (0.2 mL
      of preservative-free normal saline; n = 75) 60 seconds before undergoing needle
      insertion. This phase of the study had a randomized, double-blind, placebo
      controlled design. In the second phase, an unblinded, nonconcurrent,
      nonintervention control group (n = 47) was examined to describe any effect of
      using the jet device. Patients reported pain upon administration of the jet
      device and at needle insertion using a 100-mm color analog scale (CAS). Patients
      also reported their satisfaction with this device. The physicians and nurses
      performing needle insertions were asked to rate their ability to visualize the
      vein and their satisfaction with the device. RESULTS: The mean (+/-standard
      deviation [SD]) needle insertion pain score for jet lidocaine, 28 (+/-7) mm, was
      similar to the mean needle insertion pain score for jet placebo, 34 (+/-7) mm.
      The mean needle insertion pain score for both the jet lidocaine and the jet
      placebo groups were lower than the needle insertion pain scores for the no device
      group, 52 (+/-8) mm. The majority of patients receiving the jet device reported
      that they would request this device for future needle insertions. Providers'
      ratings of their ability to visualize veins and the patient cooperation were
      similar in all three groups. CONCLUSIONS: Jet-delivered lidocaine is no more
      effective than jet-delivered placebo in providing local anesthesia for needle
      insertion. Jet lidocaine and jet placebo may provide superior analgesia compared
      to no local anesthetic pretreatment.

PMID- 19388924
TI  - Hybrid simulation combining a high fidelity scenario with a pelvic ultrasound
      task trainer enhances the training and evaluation of endovaginal ultrasound
      skills.
AB  - OBJECTIVES: In this study, an endovaginal ultrasound (US) task trainer was
      combined with a high-fidelity US mannequin to create a hybrid simulation model.
      In a scenario depicting a patient with ectopic pregnancy and hemorrhagic shock,
      this model was compared with a standard high-fidelity simulation during training
      sessions with emergency medicine (EM) residents. The authors hypothesized that
      use of the hybrid model would increase both the residents' self-reported
      educational experience and the faculty's self-reported ability to evaluate the
      residents' skills. METHODS: A total of 45 EM residents at two institutions were
      randomized into two groups. Each group was assigned to one of two formats
      involving an ectopic pregnancy scenario. One format incorporated the new hybrid
      model, in which residents had to manipulate an endovaginal US probe in a task
      trainer; the other used the standard high-fidelity simulation mannequin together
      with static photo images. After finishing the scenario, residents self-rated
      their overall learning experience and how well the scenario evaluated their
      ability to interpret endovaginal US images. Faculty members reviewed video
      recordings of the other institution's residents and rated their own ability to
      evaluate residents' skills in interpreting endovaginal US images and diagnosing
      and managing the case scenario. Visual analog scales (VAS) were used for the self
      ratings. RESULTS: Compared to the residents assigned to the standard simulation
      scenario, residents assigned to the hybrid model reported an increase in their
      overall educational experience (Delta VAS = 10, 95% confidence interval [CI] = 4
      to 18) and felt the hybrid model was a better measure of their ability to
      interpret endovaginal US images (Delta VAS = 17, 95% CI = 7 to 28). Faculty
      members found the hybrid model to be better than the standard simulation for
      evaluating residents' skills in interpreting endovaginal US images (Delta VAS =
      13, 95% CI = 6 to 20) and diagnosing and managing the case (Delta VAS = 10, 95%
      CI = 2 to 18). Time to reach a diagnosis was similar in both groups (p = 0.053).
      CONCLUSIONS: Use of a hybrid simulation model combining a high-fidelity
      simulation with an endovaginal US task trainer improved residents' educational
      experience and improved faculty's ability to evaluate residents' endovaginal US
      and clinical skills. This novel hybrid tool should be considered for future
      education and evaluation of EM residents.

PMID- 19388925
TI  - A risk score for the management of pregnant women with increased risk of venous
      thromboembolism: a multicentre prospective study.
AB  - Patients with thrombophilia and/or a history of venous thromboembolism (VTE)
      exhibit a high risk of thrombosis during pregnancy. The present multicentre study
      prospectively assessed a prophylaxis strategy, based on a risk score, in
      pregnancies with increased risk of VTE. Among 286 patients included in the study,
      183 had a personal history of VTE (63.98%) and 191 patients (66.8%) had a
      thrombophilia marker. Eighty nine (46.6%) thrombophilic women had a personal
      history of VTE. Patients were assigned to one of three prophylaxis strategies
      according to the risk scoring system. In postpartum, all patients received low
      molecular weight heparin (LMWH) prophylaxis for at least 6 weeks. In antepartum,
      LMWH prophylaxis was prescribed to 61.8% of patients with high risk of VTE. Among
      them, 37.7% were treated in the third trimester only and 24.1% were treated
      throughout pregnancy. In this cohort, one antepartum-related VTE (0.35%) and two
      postpartum-related VTE (0.7%) occurred. No case of pulmonary embolism was
      observed during the study period. The rate of serious bleeding was 0.35%. There
      was no evidence of heparin-induced thrombocytopenia or osteoporosis. The use of a
      risk score may provide a rational decision process to implement safe and
      effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.

PMID- 19388926
TI  - Risks and benefits of splenectomy versus no splenectomy for hereditary
      spherocytosis--a personal view.
AB  - Splenectomy is indicated in hereditary spherocytosis to relieve symptoms due to
      anaemia or splenomegaly, reverse growth failure or skeletal changes due to over
      robust erythropoiesis, and prevent recurrent gallstones. A life-long risk of
      bacterial infection has been recognised for many years as a concomitant cost of
      splenectomy. The scope of this risk has expanded to include a number of organisms
      beyond the triad of pneumococcus, meningococcus, and haemophilus influenzae.
      Recently, it has been demonstrated that splenectomy also confers a significant
      risk of delayed adverse vascular events in patients with hereditary
      spherocytosis, just as it does in patients undergoing splenectomy for other
      indications. Further, these same studies demonstrated a benefit of avoiding
      splenectomy: hereditary spherocytosis patients with a spleen have significantly
      fewer adverse vascular events than unaffected family members, probably because of
      the protective effect of chronic, mild anaemia. Accordingly, this review marshals
      the evidence favouring a conservative approach to splenectomy in spherocytosis.

PMID- 19388927
TI  - Impact of tyrosine kinase inhibitors on patient outcomes in Philadelphia
      chromosome-positive acute lymphoblastic leukaemia.
AB  - Acute lymphoblastic leukaemia (ALL) is a heterogeneous disease that is often
      associated with several chromosomal and molecular abnormalities. Patients who
      have the Philadelphia (Ph) chromosome and associated BCR-ABL1 oncogene have a
      particularly poor prognosis. Currently, allogeneic haematopoietic stem cell
      transplantation (allo-HSCT) is the only known curative treatment for Ph+ ALL and
      facilitating allo-HSCT in eligible patients is a key treatment goal. However,
      many patients relapse after allo-HSCT, particularly those with measurable
      residual disease prior to transplantation, and a significant percentage of
      patients are ineligible for allo-HSCT, particularly older patients. Hence, many
      patients require additional/alternative therapies to prolong survival. Studies
      are ongoing to determine the most effective first-line drug regimens for patients
      who subsequently undergo allo-HSCT and ineligible patients. Tyrosine kinase
      inhibitors targeted to Bcr-Abl are important novel therapies for Ph+ ALL.
      Although imatinib administered in combination with chemotherapy is established as
      the current first-line strategy, relapse is common, even among allo-HSCT
      recipients. Emerging data indicate that more potent multi-targeted kinase
      inhibitors (including dasatinib, nilotinib, and bosutinib) have promising
      efficacy in the first- or second-line setting. Here, the evidence base for
      existing drug treatments for Ph+ ALL is discussed and emerging therapeutic
      strategies are explored.

PMID- 19388928
TI  - Extended diagnostic criteria for plasmacytoid dendritic cell leukaemia.
AB  - The diagnosis of plasmacytoid dendritic cell leukaemia (pDCL) is based on the
      immunophenotypic profile: CD4(+) CD56(+) lineage(neg) CD45RA(+)/RO(neg)
      CD11c(neg) CD116(low) CD123(+) CD34(neg) CD36(+) HLA-DR(+). Several studies have
      reported pDCL cases that do not express this exact profile or expressing some
      lineage antigens that could thus be misdiagnosed. This study aimed to validate
      pDCL-specific markers for diagnosis by flow-cytometry or quantitative reverse
      transcription polymerase chain reaction on bone marrow samples. Expression of
      markers previously found in normal pDC was analysed in 16 pDCL, four pDCL
      presenting an atypical phenotype (apDCL) and 113 non-pDC - lymphoid or myeloid -
      acute leukaemia. CD123 was expressed at significantly higher levels in pDCL and
      apDCL. BDCA-2 was expressed on 12/16 pDCL and on 2/4 apDCL, but was never
      detected in the 113 non-pDC acute leukaemia cases. BDCA-4 expression was found on
      13/16 pDCL, but also in 12% of non-pDC acute leukaemia. High levels of LILRA4 and
      TCL1A transcripts distinguished pDCL and apDCL from all other acute leukaemia
      (except B-cell acute lymphoblastic leukaemia for TCL1A). We thus propose a
      diagnosis strategy, scoring first the CD4(+) CD56(+/-) MPO(neg) cCD3(neg)
      cCD79a(neg) CD11c(neg) profile and then the CD123(high), BDCA-2 and BDCA-4
      expression. Atypical pDCL can be also identified this way and non-pDC acute
      leukaemia excluded: this scoring strategy is useful for diagnosing pDCL and
      apDCL.

PMID- 19388930
TI  - Identification of a novel epitope derived from CML66 that is recognized by anti
      leukaemia cytotoxic T lymphocytes.

PMID- 19388929
TI  - Inhibitor of DASH proteases affects expression of adhesion molecules in
      osteoclasts and reduces myeloma growth and bone disease.
AB  - Dipeptidyl peptidase (DPP) IV activity and/or structure homologues (DASH) are
      serine proteases implicated in tumourigenesis. We previously found that a DASH
      protease, fibroblast activation protein (FAP), was involved in osteoclast-induced
      myeloma growth. Here we further demonstrated expression of various adhesion
      molecules in osteoclasts cultured alone or cocultured with myeloma cells, and
      tested the effects of DASH inhibitor, PT-100, on myeloma cell growth, bone
      disease, osteoclast differentiation and activity, and expression of adhesion
      molecules in osteoclasts. PT-100 had no direct effects on viability of myeloma
      cells or mature osteoclasts, but significantly reduced survival of myeloma cells
      cocultured with osteoclasts. Real-time PCR array for 85 adhesion molecules
      revealed upregulation of 17 genes in osteoclasts after coculture with myeloma
      cells. Treatment of myeloma/osteoclast cocultures with PT-100 significantly
      downregulated 18 of 85 tested genes in osteoclasts, some of which are known to
      play roles in tumourigenesis and osteoclastogenesis. PT-100 also inhibited
      osteoclast differentiation and subsequent pit formation. Resorption activity of
      mature osteoclasts and differentiation of osteoblasts were not affected by PT
      100. In primary myelomatous severe combined immunodeficient (SCID)-hu mice PT-100
      reduced osteoclast activity, bone resorption and tumour burden. These data
      demonstrated that DASH proteases are involved in myeloma bone disease and tumour
      growth.

PMID- 19388931
TI  - Genotype-phenotype relationship for six common polymorphisms in genes affecting
      platelet function from 286 healthy subjects and 160 patients with mucocutaneous
      bleeding of unknown cause.
AB  - Polymorphisms affecting platelet receptors and intracellular proteins have been
      extensively studied in relation to their potential influence in thrombosis and
      haemorrhages. However, few reports have addressed their impact on platelet
      function, with contradictory results. Limitations of these studies include, among
      others, small number of patients, the platelet functional parameters analyzed and
      their known variability in the healthy population. We studied the effect of six
      polymorphisms [ITGB3 1565T > C (HPA-1), GPIBA variable number tandem repeat and
      524C > T (HPA-2), ITGA2 807C > T, ADRA2A 1780A > G, and TUBB1 Q43P] on platelet
      function in 286 healthy subjects and their potential pathogenetic role in 160
      patients with hereditary mucocutaneous bleeding of unknown cause. We found no
      effect of any of these polymorphisms on platelet aggregation, secretion, PFA-100,
      and thrombin generation in platelet rich plasma. Furthermore, patients and
      controls showed no significant differences in the frequency of any of these
      polymorphisms. Thus, our study demonstrated that polymorphisms in genes affecting
      platelet function do not influence significantly major platelet functions and
      appear irrelevant in the pathogenesis of bleeding disorders.

PMID- 19388932
TI  - Advances in the understanding of congenital amegakaryocytic thrombocytopenia.
AB  - Congenital amegakaryocytic thrombocytopenia (MIM #604498) is an extremely rare
      inherited bone marrow failure syndrome, usually presenting as a severe
      thrombocytopenia at birth due to ineffective megakaryocytopoiesis and no
      characteristic physical anomalies. Usually the isolated thrombocytopenia
      progresses to pancytopenia during the first years of life. The only curative
      therapy to date is haematopoietic stem cell transplantation. Most of the cases of
      congenital amegakaryocytic thrombocytopenia are caused by defective expression or
      function of the thrombopoietin receptor due to homozygous or compound
      heterozygous mutations in the gene MPL. The essential roles of thrombopoietin as
      a lineage specific regulator of platelet production and as a regulator of
      haematopoietic stem cell function are reflected in the haematological defects
      seen in affected individuals.

PMID- 19388933
TI  - CMC-544 (inotuzumab ozogamicin) shows less effect on multidrug resistant cells:
      analyses in cell lines and cells from patients with B-cell chronic lymphocytic
      leukaemia and lymphoma.
AB  - The effect of CMC-544, a calicheamicin-conjugated anti-CD22 monoclonal antibody,
      was analysed in relation to CD22 and P-glycoprotein (P-gp) in B-cell chronic
      lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) in vitro. The cell
      lines used were CD22-positive parental Daudi and Raji, and their P-gp positive
      sublines, Daudi/MDR and Raji/MDR. Cells obtained from 19 patients with B-cell CLL
      or NHL were also used. The effect of CMC-544 was analysed by viable cell count,
      morphology, annexin-V staining, and cell cycle distribution. A dose-dependent,
      selective cytotoxic effect of CMC-544 was observed in cell lines that expressed
      CD22. CMC-544 was not effective on Daudi/MDR and Raji/MDR cells compared with
      their parental cells. The MDR modifiers, PSC833 and MS209, restored the cytotoxic
      effect of CMC-544 in P-gp-expressing sublines. In clinical samples, the cytotoxic
      effect of CMC-544 was inversely related to the amount of P-gp (P = 0.003), and to
      intracellular rhodamine-123 accumulation (P < 0.001). On the other hand, the
      effect positively correlated with the amount of CD22 (P = 0.010). The effect of
      CMC-544 depends on the levels of CD22 and P-gp. Our findings will help to predict
      the clinical effectiveness of this drug on these B-cell malignancies, suggesting
      a beneficial effect with combined use of CMC-544 and MDR modifiers.

PMID- 19388934
TI  - The protein kinase C agonist PEP005 increases NF-kappaB expression, induces
      differentiation and increases constitutive chemokine release by primary acute
      myeloid leukaemia cells.
AB  - Acute myeloid leukaemia (AML) cells show constitutive release of several
      chemokines that occurs in three major clusters: (I) chemokine (C-C motif) ligand
      (CCL)2-4/chemokine (C-X-C motif) ligand (CXCL)1/8, (II) CCL5/CXCL9-11 and (III)
      CCL13/17/22/24/CXCL5. Ingenol-3-angelate (PEP005) is an activator of protein
      kinase C and has antileukaemic and immunostimulatory effects in AML. We
      investigated primary AML cells derived from 35 unselected patients and determined
      that PEP005 caused a dose-dependent increase in the release of chemokines from
      clusters I and II, including several T cell chemotactic chemokines. The release
      of granulocyte-macrophage colony-stimulating factor and hepatocyte growth factor
      was also increased. CCL2-4/CXCL1/8 release correlated with nuclear factor (NF)
      kappaB expression in untreated AML cells, and PEP005-induced chemokine production
      was associated with further increases in the expression of the NF-kappaB subunits
      p50, p52 and p65. Increased DNA binding of NF-kappaB was observed during exposure
      to PEP005, and the specific NF-kappaB inhibitor BMS-345541 reduced constitutive
      chemokine release even in the presence of PEP005. Finally, PEP005 decreased
      expression of stem cell markers (CD117, CXCR4) and increased lineage-associated
      CD11b and CD14 expression. To conclude, PEP005 has a unique functional
      pharmacological profile in human AML. Previous studies have described
      proapoptotic and T cell stimulatory effects and the present study describes
      additional T cell chemotactic and differentiation-inducing effects.

PMID- 19388935
TI  - Human CD80/IL2 lentivirus-transduced acute myeloid leukaemia (AML) cells promote
      natural killer (NK) cell activation and cytolytic activity: implications for a
      phase I clinical study.
AB  - Immunotherapeutic strategies may promote T and/or natural killer (NK) cell
      cytotoxicity. NK cells have the potential to exert a powerful anti-leukaemia
      effect, as demonstrated by studies of allogeneic transplantation. We have
      previously shown that CD80/interleukin 2 (IL2) lentivirus (LV)-transduced AML
      cells stimulate in-vitro T cell activation. The present study demonstrated that
      allogeneic and autologous culture of peripheral blood mononuclear cells with
      CD80/IL2-expressing AML cells also promoted NK cell cytotoxicity. Expression of
      the activation receptors NKp30, NKp44, CD244, CD25, CD69 and HLA-DR significantly
      increased following allogeneic culture and a consistent increased expression of
      NKp30, NKp44, NKp46, NKG2D, NKG2C and CD69, and up-regulation of the cytolytic
      marker CD107a was detected following autologous culture with LV-CD80/IL2 AML
      cells. Furthermore, increased NK cell lysis of K562 and primary AML blasts was
      detected. The lytic activity increased by twofold against K562 (from 46.6% to
      90.4%) and allogeneic AML cells (from 11.8% to 20.1%) following in-vitro
      stimulation by CD80/IL2-expressing AML cells. More importantly for potential
      therapeutic applications, lysis of primary AML cells by autologous NK cells
      increased by more than 40-fold (from 0.4% to 22.5%). These studies demonstrated
      that vaccination of patients with CD80/IL2-transduced AML cells could provide a
      powerful strategy for T/NK cell-mediated stimulation of anti-leukaemic
      immunological responses.

PMID- 19388936
TI  - Biological functions and therapeutic use of erythropoiesis-stimulating agents:
      perplexities and perspectives.
AB  - Randomized clinical studies, carried out in patients with haematological
      malignancies and with solid tumours, have consistently demonstrated that
      treatment with recombinant human erythropoietin (Epo) increases haemoglobin
      levels, reduces blood transfusion requirements, and improves the quality of life.
      In addition, identification of erythropoietin receptor (EpoR) expression on many
      types of non-erythroid and cancer cells has spurred an interest in the extra
      haematological activities of Epo itself and other erythropoiesis-stimulating
      agents (ESAs). Epo and its derivatives have emerged as major tissue-protective
      cytokines in ischaemic and degenerative damage of cardiovascular, neurological
      and renal diseases, while their angiogenetic and immunomodulatory properties
      indicate that their therapeutic potential may extend well beyond erythropoiesis
      alone. Both preclinical and clinical data, however, have suggested that they may
      contribute to tumour progression and prejudice survival when administered to
      anaemic cancer patients, though the results are equivocal and the assumed
      mechanisms by which tumour growth could be promoted are not fully understood.
      While these findings offer new perspectives, they nonetheless demand caution in
      the employment of ESAs. Further, well-designed experimental and clinical studies
      are warranted.

PMID- 19388937
TI  - Beta2-microglobulin is a better predictor of treatment-free survival in patients
      with chronic lymphocytic leukaemia if adjusted according to glomerular filtration
      rate.
AB  - Even in the era of newer and sophisticated prognostic markers, beta(2)
      microglobulin (B2M) remains a simple but very powerful predictor of treatment
      free survival (TFS) and overall survival (OS) in patients with chronic
      lymphocytic leukaemia (CLL). However, B2M levels are heavily influenced by the
      patient's glomerular filtration rate (GFR) and this study aimed to evaluate
      whether GFR-adjusted B2M (GFR-B2M) had improved prognostic value compared to
      unadjusted B2M in a cohort of over 450 consecutive CLL patients from two separate
      institutions. Multivariate analysis identified a significantly shorter TFS in
      patients who were ZAP-70 + (P < 0.001), with increased GFR-B2M (P < 0.001), and
      del(11q) or del(17p) as detected by fluorescence in situ hybridization (FISH; P <
      0.001). When OS was evaluated by multivariate analysis, age 65 years or older (P
      < 0.001) and poor risk FISH abnormalities (P < 0.001) had a confirmed adverse
      prognostic impact, but the predictive value of GFR-B2M was lost in the validation
      analysis. In all survival models, B2M did not attain independent significance
      unless GFR-B2M was eliminated from the analysis. In conclusion, GFR-B2M is a
      better predictor of TFS than unadjusted B2M in CLL patients.

PMID- 19388938
TI  - Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and
      chronic myelomonocytic leukaemia.
AB  - The myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal
      haematological diseases characterized by ineffective haematopoiesis and
      predisposition to acute myeloid leukaemia (AML). The pathophysiology of MDSs
      remains unclear. A definition of the molecular biology of MDSs may lead to a
      better classification, new prognosis indicators and new treatments. We studied a
      series of 40 MDS/AML samples by high-density array-comparative genome
      hybridization (aCGH). The genome of MDSs displayed a few alterations that can
      point to candidate genes, which potentially regulate histone modifications and
      WNT pathways (e.g. ASXL1, ASXL2, UTX, CXXC4, CXXC5, TET2, TET3). To validate some
      of these candidates we studied the sequence of ASXL1. We found mutations in the
      ASXL1 gene in four out of 35 MDS patients (11%). To extend these results we
      searched for mutations of ASXL1 in a series of chronic myelomonocytic leukaemias,
      a disease classified as MDS/Myeloproliferative disorder, and found mutations in
      17 out of 39 patients (43%). These results show that ASXL1 might play the role of
      a tumour suppressor in myeloid malignancies.

PMID- 19388939
TI  - Leukaemia cutis with chronic myelomonocytic leukaemia.

PMID- 19388940
TI  - Images in haematology. Toxoplasma gondii in the bone marrow after pancreas-kidney
      transplantation.

PMID- 19388941
TI  - Hypereosinophilia with a low blast count as the initial manifestation of acute
      myeloid leukaemia with RUNX1-RUNX1T1.

PMID- 19388942
TI  - VEGF/KDR loop is a target of AG1296 in acute myeloid leukaemia showing FLT3
      internal tandem duplications.

PMID- 19388943
TI  - Human genetics and resistance to parasitic infection.

PMID- 19388944
TI  - Approaches to the identification of susceptibility genes.
AB  - Although previous studies have revealed a great deal about the genetic basis of
      susceptibility and resistance to parasite infection, there is now an opportunity
      to considerably enhance understanding through genome-wide association mapping.
      The application of association mapping to complex inheritance has recently become
      achievable given reduced costs, sophisticated genotyping platforms and powerful
      statistical methods which build upon increased knowledge of the linkage
      disequilibrium structure of the human genome. Linkage mapping and related
      approaches remain useful for the localization of the rarer genetic variants and
      candidate region association studies can be a very cost-effective route to
      progress. However, genome-wide association offers the greatest promise, despite
      the challenges posed by phenotype complexity, ensuring genotype coverage/quality
      and robust statistical analysis. The available approaches for mapping genes
      underlying susceptibility are reviewed here, emphasizing their relative merits
      and drawbacks and highlighting specific software tools and resources that enable
      successful mapping.

PMID- 19388945
TI  - Genetics of susceptibility to Plasmodium falciparum: from classical malaria
      resistance genes towards genome-wide association studies.
AB  - Plasmodium falciparum represents one of the strongest selective forces on the
      human genome. This stable and perennial pressure has contributed to the
      progressive accumulation in the exposed populations of genetic adaptations to
      malaria. Descriptive genetic epidemiology provides the initial step of a logical
      procedure of consequential phases spanning from the identification of genes
      involved in the resistance/susceptibility to diseases, to the determination of
      the underlying mechanisms and finally to the possible translation of the acquired
      knowledge in new control tools. In malaria, the rational development of this
      strategy is traditionally based on complementary interactions of heterogeneous
      disciplines going from epidemiology to vaccinology passing through genetics,
      pathogenesis and immunology. New tools including expression profile analysis and
      genome-wide association studies are recently available to explore the complex
      interactions of host-parasite co-evolution. Particularly, the combination of
      genome-wide association studies with large multi-centre initiatives can overcome
      the limits of previous results due to local population dynamics. Thus, we
      anticipate substantial advances in the interpretation and validation of the
      effects of genetic variation on malaria susceptibility, and thereby on molecular
      mechanisms of protective immune responses and pathogenesis.

PMID- 19388947
TI  - Immune and genetic aspects of asthma, allergy and parasitic worm infections:
      evolutionary links.
AB  - There are important parallels in the immunobiology of allergy and asthma, and of
      the human host's response to parasitic worms. Th-2 immune actions with 'weep and
      sweep' mucosal biology are common to both - pathological in the first and
      protective in the second. Common up-regulating genetic variants of Th-2 immunity,
      notably in IL13 and STAT6, predict increased risk of asthma and allergy, but
      diminished intensity of infection by Ascaris and Schistosoma. Endemic exposures
      of humans to parasitic worms may have been one evolutionary force selecting for
      genetic variants that promote asthma and allergy.

PMID- 19388946
TI  - Genetics and visceral leishmaniasis: of mice and man.
AB  - Ninety per cent of the 500,000 annual new cases of visceral leishmaniasis (VL)
      occur in India/Bangladesh/Nepal, Sudan and Brazil. Importantly, 80-90% of human
      infections are sub-clinical or asymptomatic, usually associated with strong cell
      mediated immunity. Understanding the environmental and genetic risk factors that
      determine why two people with the same exposure to infection differ in
      susceptibility could provide important leads for improved therapies. Recent
      research using candidate gene association analysis and genome-wide linkage
      studies (GWLS) in collections of families from Sudan, Brazil and India have
      identified a number of genes/regions related both to environmental risk factors
      (e.g. iron), as well as genes that determine type 1 vs. type 2 cellular immune
      responses. However, until now all of the allelic association studies carried out
      have been underpowered to find genes of small effect sizes (odds ratios or OR <
      2), and GWLS using multicase pedigrees have only been powered to find single
      major genes, or at best oligogenic control. The accumulation of large DNA banks
      from India and Brazil now makes it possible to undertake genome-wide association
      studies (GWAS), which are ongoing as part of phase 2 of the Wellcome Trust Case
      Control Consortium. Data from this analysis should seed research into novel genes
      and mechanisms that influence susceptibility to VL.

PMID- 19388948
TI  - Genetic variation in resistance to mixed, predominantly Teladorsagia circumcincta
      nematode infections of sheep: from heritabilities to gene identification.
AB  - In cool temperate areas, such as Scotland, sheep are infected by a variety of
      nematodes but the dominant nematode is Teladorsagia circumcincta. Resistant
      animals have one or more of the following features: fewer adult nematodes, more
      inhibited larvae, shorter adult nematodes and decreased production of nematode
      eggs. In lambs at the end of the first grazing season, the heritability of adult
      worm length is very strong, whereas the heritability of egg production is
      moderate. The heritability of worm number is low while there is no detectable
      genetic variation in the number of inhibited larvae. The major mechanisms
      underlying resistance to T. circumcincta appear to be the IgA mediated
      suppression of worm growth and the mast cell mediated regulation of worm number.
      Mast cell responses are slow to develop, possibly because they are responsible
      for protein loss and reduced growth of the host. Two genes have been repeatedly
      associated with resistance to T. Circumcincta: the MHC class II DRB1 locus on
      chromosome 20 and the interferon-gamma locus on chromosome 3. Although the
      causative mutations are still unknown both genes are plausible candidates.

PMID- 19388949
TI  - Concepts, controversies, consensus, and conclusions: preface.

PMID- 19388950
TI  - Is the prevalence of periodontitis in the USA in decline?

PMID- 19388951
TI  - Microbial testing in periodontics: value, limitations and future directions.

PMID- 19388952
TI  - One-stage, full-mouth disinfection: fiction or reality?

PMID- 19388954
TI  - Risk calculation and periodontal outcomes.

PMID- 19388955
TI  - Periodontal disease and nutrition: separating the evidence from current fads.

PMID- 19388953
TI  - Saliva as a diagnostic tool for periodontal disease: current state and future
      directions.

PMID- 19388956
TI  - Application of lasers in periodontics: true innovation or myth?

PMID- 19388957
TI  - The use of biologic mediators and tissue engineering in dentistry.

PMID- 19388958
TI  - Decision making in implant dentistry: an evidence-based and decision-analysis
      approach.

PMID- 19388959
TI  - Not all roads lead to Rome-a review of quality of life measurement in adults with
      diabetes.
AB  - AIMS: Quality of life (QoL) is recognized widely as an important health outcome
      in diabetes, where the burden of self-management places great demands on the
      individual. However, the concept of QoL remains ambiguous and poorly defined. The
      aim of our review is to clarify the measurement of QoL in terms of
      conceptualization, terminology and psychometric properties, to review the
      instruments that have been used most frequently to assess QoL in diabetes
      research and make recommendations for how to select measures appropriately.
      METHODS: A systematic literature search was conducted to identify the ten
      measures most frequently used to assess QoL in diabetes research (including
      clinical trials) from 1995 to March 2008. RESULTS: Six thousand and eight-five
      abstracts were identified and screened for instrument names. Of the ten
      instruments most frequently used to assess 'QoL', only three actually do so [i.e.
      the generic World Health Organization Quality of Life (WHOQOL) and the diabetes
      specific Diabetes Quality of Life (DQOL) and Audit of Diabetes-Dependent Quality
      of Life (ADDQoL)]. Seven instruments more accurately measure health status [Short
      Form 36 (SF-36), EuroQoL 5-Dimension (EQ-5D)], treatment satisfaction [Diabetes
      Treatment Satisfaction Questionnaire (DTSQ)] and psychological well-being [Beck
      Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Well
      Being Questionnaire (W-BQ), Problem Areas in Diabetes (PAID)]. CONCLUSIONS: No
      single measure can suit every purpose or application but, when measures are
      selected inappropriately and data misinterpreted, any conclusions drawn are
      fundamentally flawed. If we value QoL as a therapeutic goal, we must ensure that
      the instruments we use are both valid and reliable. QoL assessment has the proven
      potential to identify ways in which treatments can be tailored to reduce the
      burden of diabetes. With careful consideration, appropriate measures can be
      selected and truly robust assessments undertaken successfully.

PMID- 19388960
TI  - Managing young people with Type 1 diabetes in a 'rave' new world: metabolic
      complications of substance abuse in Type 1 diabetes.
AB  - The taxing transition from adolescence towards adulthood intensifies the impact
      of a chronic illness such as Type 1 diabetes. It is not uncommon for young people
      with Type 1 diabetes to use recreational drugs for emotional relief to escape the
      day-to-day burden of chronic disease. Despite increasing use, especially in the
      setting of 'rave' parties, there is professional lack of understanding of the
      impact of recreational drug use on glycaemia and metabolic complications. The
      current review describes the prevalence of substance abuse in Type 1 diabetes and
      the acute impact of designer drugs on its management. We propose a practical
      approach to improve care of young people with Type 1 diabetes using designer
      drugs.

PMID- 19388961
TI  - Pregravid body mass index as a predictor of gestational diabetes mellitus.
AB  - AIMS: It has been well documented that overweight or obesity before pregnancy is
      a strong predictor of gestational diabetes mellitus (GDM). The aim of this study
      was to assess the risk of GDM in women who were classified on the basis of
      pregravid body mass index (BMI) as normal weight and underweight. SUBJECTS AND
      METHODS: We analysed medical records of 1121 women with GDM who were referred to
      the Outpatient Clinic for Diabetic Pregnant Women in Szczecin (north-west part of
      Poland) between January 2001 and December 2005. The control group consisted of
      1011 healthy pregnant women. All the women were Caucasian, were aged > or = 18
      years and had single pregnancies. RESULTS: The cut point for BMI as a risk
      indicator for GDM was 22.85 kg/m(2) (odds ratio = 1.91; 95% confidence interval
      1.5-2.1; sensitivity 47.8%, specificity 65.9%). In all of the analysed BMI
      ranges, except for the underweight group, significant relationships between
      pregravid BMI and GDM were found and BMI was the strongest predictor for GDM
      treated with insulin. Of all women with GDM, 25.7% were treated with insulin. The
      percentage of women requiring insulin therapy significantly increased with an
      increase of BMI across all studied categories. CONCLUSIONS: Not only in
      overweight but also in normal-weight women, the risk for GDM increases with
      increases in pregravid BMI and adjustment for confounding variables (age, prior
      GDM and parity) did not influence this relationship. Pregravid BMI is a strong
      predictor for GDM requiring insulin treatment.

PMID- 19388962
TI  - Decreasing concentration of interstitial glucose in REM sleep in subjects with
      normal glucose tolerance.
AB  - AIMS: Sleep is divided into two major stages, non-rapid eye movement (NREM) and
      rapid eye movement (REM), which are distinct in various neuroendocrine respects.
      NREM/REM cycles influence insulin and glucagon secretion; however, glucose
      concentrations in REM compared with NREM have not been directly explored. The aim
      was to investigate the differences in glucose concentrations in interstitial
      fluid (IGC) between NREM/REM cycles using a continuous glucose monitoring system
      (CGMS). METHODS: Thirteen subjects were eligible for analysis out of the 28
      enrolled. All underwent standard polysomnography for the assessment of sleep
      stages and the exclusion of sleep apnoea syndrome with CGMS and subsequent
      morning oral glucose tolerance test (exclusion of glucose intolerance or
      diabetes). RESULTS: The IGC in REM fell in 12 out of the 13 subjects, whereas the
      IGC in NREM increased in eight out of the 13 subjects. Therefore, the mean change
      of IGC differed in direction between sleep stages: -0.028 (-0.045 to -0.011) for
      REM vs. 0.005 (-0.012 to 0.017) for NREM [median (QR), P = 0.007, n = 13], with
      the mean difference of 0.038 mmol/l x 5 min(-1) (95% confidence interval 0.012,
      0.064). The mean glucose concentration in REM sleep was lower than in NREM: 4.29
      +/- 1.00 vs. 4.53 +/- 0.90 mmol/l (mean +/- sd, P = 0.003, n = 13). CONCLUSIONS:
      The decrease in IGC in REM compared with NREM sleep, with lower absolute values,
      may arise from different physiological events observed in these sleep stages. The
      REM-related decline in glucose concentrations may be a risk factor for nighttime
      hypoglycaemia.

PMID- 19388963
TI  - Factors determining normalization of glucose intolerance in middle-aged Swedish
      men and women: a 8-10-year follow-up.
AB  - AIMS: To examine factors in middle-aged Swedish men and women predicting the
      conversion from a state of abnormal glucose regulation to normal glucose
      tolerance (NGT) after 8-10 years. METHODS: At baseline 3128 men and 4821 women,
      aged 35-56 years, without previously diagnosed diabetes underwent an oral glucose
      tolerance test and completed a questionnaire. At follow-up, 2383 men and 3329
      women were re-examined. The study group consisted of 156 men and 124 women with
      impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both at
      baseline. RESULTS: The rate of reversal to NGT from IFG or IGT was similar
      regardless of gender. In participants having IFG or IGT, reversal to NGT was
      predicted by low fasting and 2-h insulin, homeostasis model assessment of insulin
      resistance and of pancreatic beta cell function, body mass index and waist
      circumference without differences between gender and baseline glucose tolerance
      group. Low 2-h glucose, however, predicted reversal to NGT in men with IFG at
      baseline, but not in men with IGT at baseline, or in women with either IFG or IGT
      at baseline. Men reverting to NGT had higher coffee consumption and women had
      higher baseline leisure-time physical activity. In multiple logistic regression,
      including all participants, low fasting and 2-h glucose remained independent
      predictors of reverting to NGT. CONCLUSIONS: Factors predicting reversal to NGT
      were measures correlated with low insulin resistance, but also lower insulin
      secretion, perhaps indicating a lower pancreatic beta cell workload in those who
      reverted. In men, but not in women, low 2-h glucose was of predictive value.

PMID- 19388964
TI  - Metabolic syndrome and short-term heart rate variability in young adults. The
      cardiovascular risk in young Finns study.
AB  - AIMS: Heart rate variability (HRV) can be used to estimate autonomic nervous
      control of the cardiovascular system. In middle-aged subjects, the metabolic
      syndrome (MetS) is associated with lower HRV. We hypothesized that alterations in
      autonomic balance are already present in young adults with the MetS, and analysed
      the association of short-term HRV with the MetS (using the National Cholesterol
      Education Program definition), in 1889 subjects aged 24-39 years. METHODS: Short
      term (3 min) HRV analysis included high-frequency (HF), low-frequency (LF) and
      total (TP) spectral components of HRV and LF/HF ratio. RESULTS: The presence of
      the MetS was associated with lower HF, LF and TP in men and women, and with
      higher LF/HF ratio in women. In men, waist circumference was the strongest
      individual MetS component that associated with HRV. After adjustments for age and
      heart rate, MetS was associated with lower HF and higher LF/HF ratio in women,
      but only with a lower TP in men (all P < 0.05). CONCLUSIONS: MetS is associated
      with lower HRV in young adults. The individual components of MetS are
      differentially associated with HRV in men and in women. Our results are
      consistent with lower vagal activity and a possible increase in sympathetic
      predominance in women with the MetS. This sex difference in vagal activity and
      sympathovagal balance may partly explain the greater increase in cardiovascular
      risk associated with MetS in women than in men.

PMID- 19388965
TI  - Altered respiratory function is associated with increased metabolic risk,
      independently of adiposity, fitness and physical activity.
AB  - AIMS: Reduced lung function is associated with an adverse metabolic risk profile,
      even after adjusting for body fatness. However, previous observations may have
      been confounded by aerobic fitness and physical activity. This study aimed to
      examine the association between lung function and both metabolic risk and insulin
      resistance in a cohort of White British adults with a family history of Type 2
      diabetes, and to explore the extent to which these associations are independent
      of body fatness, aerobic fitness (VO(2max)) and objectively measured physical
      activity. METHODS: Adults (n = 320, mean age 40.4 +/- 6.0 years) underwent
      measurement of physical activity energy expenditure (PAEE), spirometry [forced
      expiratory volume in 1 s (FEV(1))] and forced vital capacity (FVC), aerobic
      fitness (predicted VO(2max)), and anthropometric and metabolic status at baseline
      and again after 1 year (n = 257) in the ProActive trial. Clustered metabolic risk
      was calculated by summing standardized values for triglycerides, fasting insulin,
      fasting glucose, blood pressure and the inverse of high-density lipoprotein
      cholesterol. A cross-sectional analysis using linear regression with repeated
      measures was performed. RESULTS: Both FEV(1) and FVC were inversely and
      statistically significantly associated with metabolic risk and insulin resistance
      after adjusting for age, sex, smoking status, height, PAEE and fitness. The
      associations with metabolic risk remained significant after adjusting for
      measures of body fatness, but those with insulin resistance did not. CONCLUSIONS:
      Reduced lung function was associated with increased metabolic risk in this cohort
      of carefully characterized at-risk individuals. This association was independent
      of overall and central body fatness, objectively measured physical activity and
      aerobic fitness.

PMID- 19388966
TI  - The prevalence of Type 2 diabetes and its associated health problems in a
      community-dwelling elderly population.
AB  - AIMS: Prevalence estimates of Type 2 diabetes and its associated health problems
      in elderly populations are rare, especially in the very elderly. METHODS: A
      sample of 15 095 community-dwelling older people aged > or = 75 years were
      assessed. Type 2 diabetes and associated health problems were identified using
      self-reporting, general practitioner records, drug histories, and blood and urine
      measurements. RESULTS: There were 1177 people identified as having Type 2
      diabetes mellitus, giving an overall prevalence of 7.8% (95% confidence interval
      7.1, 8.5), 9.4% (8.4, 10.5) for men and 6.8% (6.1, 7.6) for women. The age, sex
      and smoking adjusted odds ratios for various health problems, comparing people
      with and without diabetes were: low vision 1.6 (1.3, 1.9), proteinuria 1.7 (1.4,
      2.1), chronic kidney disease stage 4 or 5 1.5 (1.0, 2.1), angina 1.3 (1.1, 1.6),
      myocardial infarction 1.5 (1.2, 1.8), cerebrovascular event 2.0 (1.8, 2.1) and
      foot ulceration 1.7 (1.2, 2.4). CONCLUSIONS: The prevalence of Type 2 diabetes is
      not high in community-dwelling older people, but diabetes was a contributory
      factor to a number of health problems.

PMID- 19388967
TI  - Predictors of future fasting and 2-h post-OGTT plasma glucose levels in middle
      aged men and women-the Inter99 study.
AB  - AIMS: Screening and prevention strategies for Type 2 diabetes require insight
      into the aetiological and potentially different risk factors leading to early
      impairments of fasting plasma glucose (FPG) and 2-h post-load plasma glucose
      (2hPG) levels. We studied whether risk factors predicting subtle elevations of
      FPG levels were different from those predicting elevations of 2hPG levels in men
      and women. METHODS: We used baseline and 5-year follow-up data from middle-aged
      men and women with normal glucose tolerance (NGT) at baseline in the Danish
      population-based Inter99 study (n = 3164). Anthropometric and non-anthropometric
      baseline predictors of the 5-year FPG and 2hPG levels were estimated in linear
      regression models stratified by gender. RESULTS: In men, but not in women,
      smoking and family history of diabetes predicted increased FPG levels, whereas
      high physical activity predicted a decline in 2hPG levels. Among the
      anthropometric variables, large waist circumference was the strongest predictor
      of increased FPG levels in men, whereas high body mass index (BMI) was the
      strongest predictor of increased FPG levels in women. In both men and women, BMI
      and waist circumference were equally strong in predicting 2hPG levels.
      Furthermore, short height predicted increased 2hPG levels in men, and short
      height and low hip circumference predicted increased 2hPG levels in women.
      CONCLUSIONS: Risk factors that predict future FPG levels are different from those
      predicting future 2hPG levels. Furthermore, different risk factors predict
      glycaemic levels in men compared with women. These findings indicate that
      different aetiological pathways may lead to Type 2 diabetes in men and women.

PMID- 19388968
TI  - Carotid intima-media thickness and apolipoprotein B/apolipoprotein A-I ratio in
      middle-aged patients with Type 2 diabetes.
AB  - AIMS: To explore the association between carotid intima-media thickness (IMT) and
      the apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio compared with
      conventional lipids in middle-aged patients with Type 2 diabetes. METHODS: We
      analysed data from 247 patients with Type 2 diabetes, aged 55-66 years, in the
      Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in
      Primary care (CARDIPP-1) study. Primary care nurses measured blood pressure and
      anthropometric characteristics. Blood samples were taken for laboratory analyses.
      The carotid IMT was determined by ultrasonography at the University Hospital in
      Linkoping and at the County Hospital Ryhov, Jonkoping, Sweden. RESULTS: The
      ApoB/apoA-I ratio (r = 0.207, P = 0.001), apoB (r = 0.166, P = 0.009) and non
      high-density lipoprotein cholesterol (non-HDL-c) (r = 0.129, P = 0.046)
      correlated with IMT. Conventional lipids, high-sensitivity C-reactive protein
      (hsCRP), glycated haemoglobin (HbA(1c)) and systolic blood pressure were not
      significantly correlated to IMT. A stepwise logistic regression analysis was
      conducted with IMT as the dependent variable and the apoB/apoA-I ratio, HbA(1c),
      hsCRP, low-density lipoprotein cholesterol (LDL-c), total cholesterol, non-HDL-c
      and treatment with statins as independent variables. Following adjustment for age
      and gender, only the apoB/apoA-I ratio remained significantly associated with IMT
      (odds ratio 4.3, 95% confidence intervals 1.7-10.8, P = 0.002). CONCLUSIONS: We
      conclude that there was a significant association between the apoB/apoA-I ratio
      and IMT in middle-aged patients with Type 2 diabetes. The association was
      independent of conventional lipids, hsCRP, glycaemic control and use of statins.

PMID- 19388969
TI  - Incidence and characteristics of lower limb amputations in people with diabetes.
AB  - AIMS: To estimate the incidence, characteristics and potential causes of lower
      limb amputations in France. METHODS: Admissions with lower limb amputations were
      extracted from the 2003 French national hospital discharge database, which
      includes major diagnoses and procedures performed during hospital admissions. For
      each patient, diabetes was defined by its record in at least one admission with
      or without lower limb amputation in the 2002-2003 databases. RESULTS: In 2003, 17
      551 admissions with lower limb amputation were recorded, involving 15 353
      persons, which included 7955 people with diabetes. The crude incidence of lower
      limb amputation in people with diabetes was 378/100 000 (349/100 000 when
      excluding traumatic lower limb amputation). The sex and age standardized
      incidence was 12 times higher in people with than without diabetes (158 vs.
      13/100 000). Renal complications and peripheral arterial disease and/or
      neuropathy were reported in, respectively, 30% and 95% of people with diabetes
      with lower limb amputation. Traumatic causes (excluding foot contusion) and bone
      diseases (excluding foot osteomyelitis) were reported in, respectively, 3% and 6%
      of people with diabetes and lower limb amputation, and were 5 and 13 times more
      frequent than in people without diabetes. CONCLUSIONS: We provide a first
      national estimate of lower limb amputation in France. We highlight its major
      impact on people with diabetes and its close relationship with peripheral
      arterial disease/neuropathy and renal complications in the national hospital
      discharge database. We do not suggest the exclusion of traumatic causes when
      studying the epidemiology of lower limb amputation related to diabetes, as
      diabetes may contribute to amputation even when the first cause appears to be
      traumatic.

PMID- 19388970
TI  - Association between plasma osteoprotegerin concentrations and urinary albumin
      excretion in Type 2 diabetes.
AB  - AIMS: Osteoprotegerin (OPG) is a recently identified inhibitor of bone
      resorption. Recent studies indicate that OPG is also associated with endothelial
      dysfunction in Type 2 diabetes. The aim was to investigate the relationship
      between plasma OPG levels and urinary albumin excretion (UAE) in Type 2 diabetic
      patients. METHODS: This study included 154 newly diagnosed Type 2 diabetic
      patients and 46 healthy subjects. Plasma OPG and 24-h UAE were measured. High
      resolution ultrasound was used to measure flow-mediated (endothelium-dependent
      arterial) dilation (FMD). RESULTS: Compared with the normoalbuminuric subgroup,
      OPG levels in the microalbuminuric subgroup were significantly higher, and OPG
      levels in macroalbuminuria subgroup were significantly higher than those in the
      normoalbuminuria and albuminuria subgroups. Multiple regression analysis showed
      that only FMD (r = -0.26), C-reactive protein (r = 0.23), fasting blood glucose
      (r = 0.25), 2-h blood glucose (r = 0.21), HbA(1c) (r = 0.28), UAE (r = 0.27) and
      retinopathy (r = 0.27) were significant factors associated with OPG. Pearson's
      correlation analyses showed a positive correlation between OPG and logUAE (r =
      0.440) and negative correlations between OPG and FMD (r = -0.284), and between
      FMD and logUAE (r = -0.602). CONCLUSIONS: Plasma OPG levels are significantly
      associated with UAE in Type 2 diabetic patients.

PMID- 19388971
TI  - Road traffic accident risk in patients with diabetes mellitus receiving blood
      glucose-lowering drugs. Prospective follow-up study.
AB  - AIM: To investigate, at a national level, whether patients using insulin or oral
      glucose-lowering agents had an increased risk of road traffic accidents compared
      with non-users. METHODS: All Norwegians aged 18-69 years (3.1 million) were
      followed from April 2004 until September 2006. Information on drug prescriptions,
      road traffic accidents and emigration/death was obtained from the following
      population-based registries: the Prescription Database, the Road Accident
      Registry and the Central Population Registry. The exposure period was the time
      from the first prescription of insulin or oral glucose-lowering agent during the
      study period. The incidence of accidents in the exposed person-time was compared
      with the incidence of accidents in the unexposed person-time by standardized
      incidence ratio (SIR). RESULTS: During the study period, 20 494 road traffic
      accidents with personal injuries were registered in Norway. One hundred and
      eighty-three accidents were registered for insulin users not taking oral glucose
      lowering agents and 219 for users of oral blood glucose-lowering drugs without
      insulin. The SIR (95% confidence interval) for all ages and both genders combined
      were: insulin 1.4 (1.2-1.6), oral glucose-lowering agents 1.2 (1.0-1.3) and users
      of drugs for peptic ulcer and gastro-oesophageal reflux disease (negative
      comparators) 1.3 (1.2-1.4). The highest SIRs were found among the youngest
      insulin users (18-34 years old). CONCLUSIONS: A slightly increased risk of being
      involved in a road traffic accident was observed for drivers prescribed insulin,
      while no increased risk was observed for drivers prescribed oral glucose-lowering
      agents. The increased risk observed for insulin users was similar to that
      observed for users of drugs for peptic ulcer and gastro-oesophageal reflux
      disease.

PMID- 19388972
TI  - Nateglinide combination therapy with basal insulin and metformin in patients with
      Type 2 diabetes.
AB  - AIMS: To compare the effect of adding nateglinide or placebo on postprandial
      glucose excursions (PPGEs), glycated haemoglobin (HbA(1c)), diurnal glucose
      profiles and hypoglycaemia in patients with Type 2 diabetes treated with the
      combination of basal insulin and metformin. RESEARCH DESIGN AND METHODS: This was
      an investigator-initiated, double-blind, randomized, parallel-group, study in
      five centres. Patients with Type 2 diabetes (n = 88, age 56.0 +/- 0.9 years,
      duration of diabetes 9.4 +/- 0.5 years, HbA(1c) 7.8 +/- 0.1%, body mass index
      32.4 +/- 0.5 kg/m(2)) treated with basal insulin and metformin entered a 24-week
      period, during which basal insulin was titrated to optimize glucose control.
      Thereafter, the patients were randomized to receive either nateglinide (120 mg
      three times daily) or placebo before their main meals for 24 weeks. RESULTS:
      During the optimization period, HbA(1c) decreased by -0.3 +/- 0.1 and -0.4 +/-
      0.2% (NS) and insulin doses increased by 10.0 IU (2.0-32.0) [0.09 IU/kg (0.02
      0.34)] and 10.0 IU (0.0-19.0) [0.11 IU/kg (0.0-0.25)] (NS) in the nateglinide and
      placebo groups. Mean postprandial glucose during weeks 20-24 averaged 9.0 +/- 0.3
      and 10.0 +/- 0.3 mmol/l in the nateglinide and placebo groups (P = 0.025) and
      mean PPGE averaged 2.4 +/- 0.2 and 3.1 +/- 0.2 mmol/l, respectively (P = 0.019).
      At 24 weeks as compared with 0 weeks, mean HbA(1c) had decreased by 0.41 +/-
      0.12% in the nateglinide group and by 0.04 +/- 0.12% in the placebo group (P =
      0.023). The frequency of confirmed, symptomatic hypoglycaemia was 7.7
      episodes/patient-year vs. 4.7 episodes/patient-year in the nateglinide and
      placebo groups (P = 0.031). CONCLUSIONS: Addition of a short-acting insulin
      secretagogue at main meals improves postprandial hyperglycaemia during
      combination therapy with basal insulin and metformin, but increases the frequency
      of hypolycaemia.

PMID- 19388973
TI  - Treatment preferences and medication adherence of people with Type 2 diabetes
      using oral glucose-lowering agents.
AB  - AIMS: Medication non-adherence is particularly common in patients with Type 2
      diabetes. We constructed a discrete-choice experiment to examine the relative
      importance of oral glucose-lowering medication features and to estimate the
      likely effect of effectiveness and side effects on medication adherence in
      patients with Type 2 diabetes in the UK and the USA. METHODS: Preferences were
      elicited using a cross-sectional, web-enabled survey. Patients with a self
      reported physician-made diagnosis of Type 2 diabetes, who were currently taking
      oral glucose-lowering medications were recruited through an existing online
      chronic-disease panel. In each discrete-choice question, patients were asked to
      choose between two hypothetical medication alternatives, each defined by
      improvement in glycated haemoglobin, frequency of mild-to-moderate hypoglycaemia,
      water retention, weight gain, mild stomach upset and medication-related
      cardiovascular risk. Patients were also asked to indicate how likely they would
      be to miss or skip doses of each hypothetical medication. RESULTS: Two hundred
      and four patients in the UK and 203 patients in the USA completed the survey.
      Preferences did not differ between the two countries. Overall, glucose control
      was the most important medication feature, followed by medication-related
      cardiovascular risk and weight gain, respectively. Water retention was not
      important to patients. Weight gain and cardiovascular risk had significant
      negative effects on likely medication adherence. CONCLUSIONS: While patients with
      Type 2 diabetes believe glucose control is important, medication side effects and
      risks influence patients' treatment choices. Medication-related weight gain and
      cardiovascular risk are significant predictors of likely medication non
      adherence.

PMID- 19388974
TI  - Are current psychometric tools suitable for measuring outcomes of diabetes
      education?
AB  - AIMS: To critically appraise the suitability, validity, reliability, feasibility
      and sensitivity to change of available psychometric tools for measuring the
      education outcomes identified in the (Australian) National Consensus on Outcomes
      and Indicators for Diabetes Patient Education. METHODS: Potentially suitable
      psychometric measurement tools were identified through a two-step process. Step
      1: a structured semi-systematic literature review and consultation with experts;
      step 2: development of inclusion criteria and a formal, purpose-designed,
      systematically derived Appraisal Checklist-from the literature and with expert
      psychometric advice-to critically appraise the identified tools for relevance,
      validity, reliability, responsiveness to change, burden, feasibility and
      acceptability. RESULTS: Searching medline, PubMed, PsycINFO and cinhal yielded 37
      diabetes-specific and generic measurement tools. Eleven of these did not address
      the research questions, leaving 26 tools. Of these, 11 assessed indicators of
      psychological adjustment; seven assessed various domains of self-determination;
      five measured self-management behaviours, for example, foot care, blood glucose
      testing and lifestyle domains; and three measured diabetes knowledge und
      understanding, respectively. When the Appraisal Checklist was applied, only three
      tools met all criteria, namely the Problem Areas in Diabetes (PAID) scale, the
      Summary of Diabetes Self-Care Activities (SDSCA) scale and the Appraisal of
      Diabetes Scale (ADS). However, a number of other suitable tools [i.e. the
      Diabetes Integration Scale (ATT19), the Diabetes Health Profile (DHP-1/18), the
      Self-Care Inventory-Revised (SCI-R), the Diabetes Management Self Efficacy Scale
      Australian/English version (DMSES-A/E), the Diabetes Empowerment Scale-Short Form
      (DES-SF)] met all except one criteria, that is, either no formal test-retest or
      no responsiveness to change data. CONCLUSIONS: Although numerous tools were
      identified, few met rigorous psychometric appraisal criteria. Issues of
      suitability, adequate psychometric testing for the intended purpose, burden and
      feasibility need to be considered before adopting tools for measuring diabetes
      education outcomes.

PMID- 19388975
TI  - A genetic diagnosis of HNF1A diabetes alters treatment and improves glycaemic
      control in the majority of insulin-treated patients.
AB  - BACKGROUND AND AIMS: Hepatocyte nuclear factor-1 alpha (HNF1A) gene mutations are
      the commonest cause of monogenic diabetes, but patients are often misdiagnosed as
      having Type 1 diabetes and started on insulin treatment. Patients with HNF1A
      diabetes are particularly sensitive to the glucose-lowering effect of
      sulphonylureas, which are the pharmacological treatment of choice. We aimed to
      assess if patients do change from insulin to sulphonylurea treatment when HNF1A
      diabetes is confirmed and the impact of this treatment change on long-term
      glycaemic control. METHODS: We investigated the clinical course of 43 patients
      who were insulin treated from diagnosis for a median 4 years (range 1-14) before
      an HNF1A gene mutation was identified. RESULTS: Thirty-four patients (79%)
      stopped insulin following genetic testing and transferred to sulphonylureas.
      Twenty-four of them (71%) remained off insulin at a median 39 months (range 17
      90) post-transfer. The 10 patients who recommenced insulin had a trend towards a
      longer duration of diabetes (18 vs. 7 years, P = 0.066) compared with those
      remaining on tablets. The median glycated haemoglobin (HbA(1c)) was good (6.9%;
      interquartile range 6.3-8.0%) in the patients who remained off insulin and 19/24
      patients (79%) achieved HbA(1c) < 7.5% or improved their pre-genetic diagnosis
      HbA(1c) by > 1.0%. Transfer off insulin was not attempted in eight patients: one
      of these was planning pregnancy and two chose to remain on insulin. CONCLUSION:
      In this observational study we found that a molecular genetic diagnosis of HNF1A
      diabetes does alter treatment in clinical practice, with 79% attempting transfer
      to sulphonylureas. Transfer to sulphonylureas was successful in the majority of
      patients without deterioration in glycaemic control.

PMID- 19388976
TI  - A national consensus on outcomes and indicators for diabetes patient education.
AB  - AIM: To develop a national evidence and consensus position on the desired goals,
      outcomes and indicators of diabetes patient education (DPE). METHODS: A mixture
      of qualitative and quantitative methods were used including: (i) literature
      reviews to identify existing definitions, issues and work in the area; (ii)
      interviews with key opinion leaders; (iii) focus groups with people with
      diabetes; (iv) a national survey of diabetes education service providers; (v) a
      systematic consultation process culminating in a national stakeholder forum.
      RESULTS: Three overarching goals were identified as the main purpose of diabetes
      patient education: (i) optimal adjustment to living with diabetes, (ii) optimal
      health outcomes and (iii) optimal cost-effectiveness (for the individual and for
      society). Given the difficulty in attributing cause and effect between education
      and clinical or cost outcomes and that mechanisms already exist for collecting
      data on clinical endpoints and surrogate indicators, the development of education
      indicators concentrated on the goal of optimal adjustment to living with
      diabetes. Four key outcomes for this goal were listed in order as either directly
      attributable to DPE or in which DPE plays a discernable role: knowledge and
      understanding, self-determination, self-management and psychological adjustment.
      CONCLUSIONS: The consensus position represents a sound evidence-informed platform
      on which diabetes education policy, programmes, data collection and research can
      be based. However, further work was required to test and make recommendations
      about applying potentially relevant psychometric tools to measure changes in the
      identified indicators.

PMID- 19388977
TI  - National guidelines for psychological care in diabetes: how mindful have we been?
AB  - AIMS: To assess the availability and types of psychological services for people
      with diabetes in the UK, compliance with national guidelines and skills of the
      diabetes team in, and attitudes towards, psychological aspects of diabetes
      management. METHODS: Postal questionnaires to team leads (doctor and nurse) of
      all UK diabetes centres (n = 464) followed by semi-structured telephone
      interviews of expert providers of psychological services identified by team
      leads. RESULTS: Two hundred and sixty-seven centres (58%) returned postal
      questionnaires; 66 (25%) identified a named expert provider of psychological
      services, of whom 53 (80%) were interviewed by telephone. Less than one-third (n
      = 84) of responding centres had access to specialist psychological services and
      availability varied across the four UK nations (P = 0.02). Over two-thirds (n =
      182) of centres had not implemented the majority of national guidelines and only
      2.6% met all guidelines. Psychological input into teams was associated with
      improved training in psychological issues for team members (P < 0.001),
      perception of better skills in managing more complex psychological issues (P < or
      = 0.01) and increased likelihood of having psychological care pathways (P < or =
      0.05). Most (81%) expert providers interviewed by telephone were under-resourced
      to meet the psychological needs of their population. CONCLUSIONS: Expert
      psychological support is not available to the majority of diabetes centres and
      significant geographical variation indicates inequity of service provision. Only
      a minority of centres meet national guidelines. Skills and services within
      diabetes teams vary widely and are positively influenced by the presence of
      expert providers of psychological care. Lack of resources are a barrier to
      service provision.

PMID- 19388978
TI  - Prevalence of diabetes mellitus and obesity in the general adult population of
      Greece: a door-to-door epidemiological study.

PMID- 19388979
TI  - An analysis of major UK newspaper articles pertaining to 'diabetes' and 'cure'
      over 1 year.

PMID- 19388980
TI  - European physicians overestimate life expectancy and the likely impact of
      interventions in individuals with Type 2 diabetes.

PMID- 19388981
TI  - Mouse orthotopic models for bladder cancer research.
AB  - Bladder cancer is a common malignancy in the urinary tract. Despite different
      therapeutic options, recurrence and progression of urothelial carcinoma after
      treatment is not uncommon. Novel therapeutic options of bladder cancer are
      urgently needed. The preclinical evaluation of new treatments requires an animal
      tumour model that mimics the human counterpart. To date, various animal
      orthotopic bladder cancer models have been described, but the reported rate of
      tumour 'take' is 30-100%. The establishment of reliable and reproducible animal
      models remains an ongoing challenge. We review different kinds of mouse models of
      orthotopic bladder cancer used in urothelial cancer studies, the methods of
      implantation, and the reported rate of tumour take. Significant progress has been
      made recently in noninvasive small animal-imaging in tumour models. It is now
      possible for researchers to investigate the effects of studied agents by
      monitoring of in vivo tumour growth directly and noninvasively, as well as
      measuring a wide range of tumour-related variables in small animals. We summarize
      the recent development in small-animal imaging for tumour detection and
      quantification.

PMID- 19388982
TI  - Optimal management of metastatic renal cell carcinoma: an algorithm for
      treatment.
AB  - The treatment of metastatic renal cell carcinoma (mRCC) has been changed by the
      introduction of targeted agents. Consideration of individual patient factors,
      such as previous treatment and prognostic risk, e.g. according to the Memorial
      Sloan-Kettering Cancer Center (MSKCC) risk criteria), can assist in ensuring that
      patients receive appropriate targeted therapies. Available clinical evidence
      shows sunitinib to be the reference standard of care for the first-line treatment
      of mRCC in patients at favourable or intermediate prognostic risk according to
      MSKCC criteria. Combined treatment with bevacizumab plus interferon-alpha can
      also be considered for the first-line treatment of mRCC in this setting. For the
      first-line treatment of poor-risk patients, temsirolimus has shown benefit in a
      phase III study, while sunitinib can also be considered. For second-line
      treatment in cytokine-refractory patients, sorafenib is recommended based on
      phase III trial results; sunitinib has also shown activity after failure of
      cytokine therapy or targeted agents. As well as antitumour activity, the
      tolerability of targeted agents should be evaluated in the context of individual
      patients, considering factors such as comorbidities and age. As our understanding
      of the activity of targeted agents for mRCC increases, we should ensure that
      these agents are used appropriately to provide patients with optimal treatment
      benefits.

PMID- 19388983
TI  - Lower urinary tract symptoms: lack of change in prevalence and help-seeking
      behaviour in two population-based surveys of women in 1991 and 2007.
AB  - OBJECTIVES: To test the hypothesis that the overt prevalence and help-seeking
      pattern for lower urinary tract symptoms (LUTS) might have changed over time, by
      comparing the prevalence of urinary incontinence (UI), overactive bladder (OAB)
      and other LUTS (principally storage symptoms) and help-seeking pattern in two
      equivalent groups of women 16 years apart. SUBJECTS AND METHODS: We compared two
      cross-sectional studies; population-based random samples of women aged >=20 years
      in the central district of Gothenburg in 1991 (2911) and 2007 (3158) were asked
      to complete similar self-administered postal questionnaires regarding UI and
      other LUTS. RESULTS: The mean (sd, range) age of the two groups was 48.1 (20.4,
      20-98) years in 1991 and 46.2 (20.0, 20-101) years in 2007, respectively. When
      comparing the two study populations there were no significant differences in the
      reported prevalence of UI, OAB or nocturia (defined as two or more voids per
      night) over time. Nocturia according to the International Continence Society
      definition was significantly more prevalent in 2007 than 1991, as was daytime
      voiding frequency of eight or more times a day. OAB dry (i.e. with no
      incontinence) was more common in 1991, while OAB wet (i.e. with incontinence) was
      more prevalent in 2007. Of the women in 1991 and 2007, 6% and 7%, respectively,
      had sought help from the healthcare system due to UI. Significantly more women in
      2007 than in 1991 stated that the presence of UI limited their social life (29%
      vs 13%, P < 0.001). CONCLUSION: LUTS are common in women and the prevalence rates
      of UI and OAB have not changed during the last 16 years. Many women still do not
      seek help from the healthcare system, and the help-seeking pattern has remained
      unchanged, despite effective treatment currently being offered.

PMID- 19388984
TI  - Laparoscopic vs open radical nephroureterectomy for upper urinary tract
      urothelial cancer: oncological outcomes and 5-year follow-up.
AB  - OBJECTIVE: To compare the oncological outcomes of laparoscopic radical
      nephroureterectomy (LNU) vs open NU (ONU) for upper urinary tract transitional
      cell carcinoma (TCC). PATIENTS AND METHODS: Between July 1999 and January 2003,
      we performed 70 LNUs and 70 ONUs for TCC of the upper urinary tract. ONU was
      reserved for patients with previous abdominal surgery or with severe cardiac
      and/or pulmonary problems. Demographic data, tumour staging and histological
      grading and rates of metastasis were recorded and compared. RESULTS: For LNU and
      ONU the mean operative durations were 240 min and 190 min, respectively. The
      definitive pathology showed a high incidence of tumour stage pT2 G2 in both LNU
      and ONU groups. The median follow-up was 60 months. In the LNU group, the 5-year
      disease-free survival (DFS) was 75%: 100% for pTa, 88% for pT1, 78% for pT2, and
      35% for pT3 (P < 0.001). In the ONU group, the 5-year DFS was 73% (LNU vs ONU, P
      = 0.037): 100% for pTa, 89% for pT1, 75% for pT2 and 31% for pT3 (P < 0.001).
      CONCLUSION: The results of our long-term controlled study support the use of LNU
      as an effective alternative to ONU in the therapy of upper urinary tract
      urothelial cancer.

PMID- 19388985
TI  - Quantitative and qualitative analysis of the recovery of potency after radical
      prostatectomy: effect of unilateral vs bilateral nerve sparing.
AB  - OBJECTIVES: To analyse the impact of a approximately 50% reduction of cavernous
      nervous tissue on the qualitative and quantitative recovery of sexual function
      after unilateral (UNS) and bilateral (BNS) nerve-sparing robotic radical
      prostatectomy (RALP), by evaluating these differences in two groups treated with
      cautery and a cautery-free technique (CFT). PATIENTS AND METHODS: UNS was defined
      as wide-excision of one neurovascular bundle (NVB). Only men aged < or =65 years
      with preoperative International Index of Erectile Function (IIEF-5) scores of >
      or =22 were included. The cautery group comprised 42 men (of case numbers 1-125)
      undergoing RALP with cautery, and the CFT group (62 men of cases 151-350) had a
      cautery-free technique along the NVB. Data were collected prospectively using
      validated self-administered questionnaires. Potency was defined as two
      affirmative answers to: do you have erections 'adequate for vaginal penetration?'
      and 'Are they satisfactory?'. Patient-reported IIEF-5 scores and quality of
      erections (i.e. an estimate of erection as 0%, 25%, 50%, 75% or 100% of
      preoperative fullness) were obtained after surgery. RESULTS: In the cautery
      group, doubling the nerve volume increased potency by 1.36 times (UNS 50% vs BNS
      68%). The results were similar in the CFT group as doubling nerve tissue
      increased potency by 1.15 times (UNS 80% and BNS 93%). At 24 months, comparing
      IIEF-5 scores, there was no difference between UNS and BNS for the cautery group,
      at 19.6 (95% confidence interval 15.7-23.5) vs 18.9 (16.6-21.0), or the CFT
      group, at 22.0 (20.2-23.8) vs 21.0 (19.8-22.1). CONCLUSIONS: Doubling the nerve
      volume only increased potency by 1.15-1.36 times for both the CFT and cautery
      groups. Furthermore, the quality of erections and IIEF-5 scores did not vary
      appreciably with doubling of nerve tissue.

PMID- 19388986
TI  - High-intensity focused ultrasound for prostate cancer: comparative definitions of
      biochemical failure.
AB  - OBJECTIVES: To compare the specificity and sensitivity of different definitions
      of biochemical failure in patients treated with high-intensity focused ultrasound
      (HIFU) for prostate cancer, to identify the most accurate predictor of clinical
      failure after HIFU. PATIENTS AND METHODS: Consecutively treated patients who
      underwent HIFU between October 1997 and July 2006 at two centres (Lyon, France;
      and Regensburg, Germany) were prospectively maintained within a central database
      and retrospectively reviewed for this study. Clinical failure was defined as a
      positive prostate biopsy after treatment, radiographic evidence of lymphatic or
      bony metastatic disease, or salvage treatment for prostate cancer (surgery,
      radiation, hormonal therapy or second HIFU). The serum prostate-specific antigen
      (PSA) values after HIFU were assessed as a biochemical surrogate of a therapeutic
      success or failure. PSA threshold values, 'PSA nadir plus', PSA velocity, PSA
      doubling time and the American Society or Therapeutic Radiotherapy and Oncology
      and Phoenix definition of biochemical failure were all considered. The
      sensitivity, specificity, positive predictive value and negative predictive value
      of each biochemical definition for predicting clinical failure were determined.
      RESULTS: The data from 285 patients (stage <or= T2, PSA <15 ng/mL, Gleason score
      <or=7) were analysed. The median (range) follow-up was 4.7 (2-10.9) years. The
      median PSA nadir was 0.13 ng/mL, which occurred at a median of 12.9 weeks after
      HIFU, and the median PSA at the last follow-up was 0.76 (1.6-2.7) ng/mL. Clinical
      failure occurred in 71 patients (25%); 24 due to a positive biopsy and 47 through
      the use of an additional therapy. Biochemical events that best predicted clinical
      failure were 'PSA nadir plus' values of 1.1-1.3 ng/mL, PSA velocities of <0.3
      ng/mL/year and PSA doubling times of 1.25-1.75 years. CONCLUSION: A new
      definition of biochemical failure that is specific to patients treated with HIFU
      therapy is established, i.e. the 'Stuttgart definition', the 'PSA nadir plus 1.2
      ng/mL'.

PMID- 19388987
TI  - Survival outcomes in men receiving androgen-deprivation therapy as primary or
      salvage treatment for localized or advanced prostate cancer: 20-year single
      centre experience.
AB  - OBJECTIVES: To evaluate the overall survival (OS) and disease-specific survival
      (DSS) in men receiving primary androgen-deprivation therapy (PADT) or salvage
      medical ADT (SADT) for prostate cancer. PATIENTS AND METHODS: After Institutional
      Review Board approval, we retrospectively reviewed patients receiving ADT for
      prostate cancer between July 1987 and June 2007. Variables included age at
      diagnosis and ADT induction, race, PSA level before ADT, ADT schedule
      (continuous/intermittent), clinical/pathological stage, hormone-refractory
      prostate cancer (HRCP) status, PADT or SADT, and deaths. RESULTS: In all, 548 men
      were analysed. The mean age at diagnosis and ADT induction were 70.1 and 72.3
      years, respectively, and 321 (58.6%) were African-American. The median PSA level
      before ADT was 16.3 ng/mL. ADT was administered continuously in 497 (90.7%)
      patients; 342 (62.4%) received PADT while 206 (37.6%) received SADT. At mean
      (range) follow-up of 81.8 (2.1-445) months, 98 (17.9%) deaths occurred; 31
      (31.6%) were cancer-specific. The OS and DSS in the PADT and SADT groups were not
      significantly different (P = 0.36 and P = 0.81, respectively). Mortality
      rates/distributions were similar between groups (P = 0.68). Multivariate
      predictors of OS and DSS included age at diagnosis (P = 0.03) and ADT induction
      (P = 0.009), tumour stage (P < 0.001), and PSA level at ADT induction (P = 0.01).
      Progression to HRPC worsened OS and DSS (both P < 0.001). CONCLUSION: PADT and
      SADT prolong survival in men with prostate cancer. HRPC portends a poor DSS. Age
      at diagnosis and ADT induction, PSA level before ADT, and disease stage predict
      both OS and DSS in this population. However, most men died from causes unrelated
      to prostate cancer, thus questioning the true value of ADT in prolonging patient
      survival.

PMID- 19388988
TI  - Retrospective analysis of the distance between the neurovascular bundle and
      prostate cancer foci in radical prostatectomy specimens: its clinical implication
      in nerve-sparing surgery.
AB  - OBJECTIVE: To analyse the distance between the ipsilateral neurovascular bundles
      (NVBs) and foci of prostate cancer (N-T distance) in specimens removed by radical
      prostatectomy (RP) and identify the predictor for N-T distance for preserving the
      ipsilateral NVB, as an accurate understanding of the anatomical relationship
      between prostate cancer foci and the NVB is necessary for establishing the
      indications for the appropriate use of nerve-sparing (NS) modifications of RP.
      PATIENTS AND METHODS: The study included 245 patients with prostate cancer who
      had RP through the perineal or retropubic approach between June 2000 and November
      2006. The analysis focused on 302 foci of prostate cancer (192 cases), which
      involved at least the posterolateral region of the prostate. The N-T distance was
      separately measured in the apex, middle and base of the prostate, and was
      correlated with the maximum diameter and Gleason score of the foci, and the
      preoperative prostate-specific antigen (PSA) level. RESULTS: The mean N-T
      distance was 2.98, 2.95 and 3.03 mm in the apex (216 foci), middle (195 foci) and
      base (80 foci), respectively. In the apex, the N-T distance was related to both
      tumour size and preoperative PSA value (P < 0.001 and P < 0.05, respectively). In
      the base, tumour size was related to the N-T distance (P < 0.01), but the
      preoperative PSA level was not related to the N-T distance. In the middle, the
      association of tumour size with N-T distance was of borderline significance (P =
      0.07). Irrespective of tumour location, the Gleason score did not contribute to
      the N-T distance. CONCLUSIONS: These findings show the basic information
      necessary when making a decision to perform NS-RP in patients with localized
      prostate cancer. The application of N-T distance could provide a better strategy
      for determining indications that warrant the use of NS RP than with the
      conventional tactile feedback approach.

PMID- 19388989
TI  - Expression of potential molecular markers in renal cell carcinoma: impact on
      clinicopathological outcomes in patients undergoing radical nephrectomy.
AB  - OBJECTIVES: To evaluate the expression levels of several potential molecular
      markers in renal cell carcinoma (RCC), to clarify the significance of these
      markers as prognostic predictors in patients undergoing radical nephrectomy (RN).
      PATIENTS AND METHODS: The study included 153 patients with clinically organ
      confined RCC undergoing RN. Expression levels of 12 proteins, including Aurora-A,
      Bcl-2, Bcl-xL, clusterin, heat-shock protein 27 (HSP27), HSP70, HSP90, Ki-67,
      matrix metalloproteinase (MMP)-2 and -9, p53 and vascular endothelial growth
      factor, in RN specimens obtained from these 153 patients were measured by
      immunohistochemical staining. RESULTS: Of the 12 markers, clusterin, HSP27, Ki
      67, MMP-2 and -9 expression were significantly associated with several
      conventional prognostic factors. Univariate analysis also identified these five
      markers as significant predictors of disease recurrence, while mode of
      presentation, pathological stage, grade and microvascular invasion were also
      significant. Of these significant factors, Ki-67 expression, pathological stage
      and microvascular invasion appeared to be independently related to disease
      recurrence. Furthermore, there were significant differences in recurrence-free
      survival according to positive numbers of these three independent factors, i.e.
      disease recurred in four of 56 patients who were negative for risk factors (7%),
      17 of 71 positive for one risk factor (24%), and 20 of 26 positive for two or
      three risk factors (77%). CONCLUSIONS: Combined evaluation of Ki-67 expression,
      pathological stage and microvascular invasion would be particularly useful for
      further refinement of the system for predicting the outcome after RN for patients
      with RCC.

PMID- 19388990
TI  - One-sided anterior urethroplasty: a new dorsal onlay graft technique.
AB  - OBJECTIVE: To investigate the feasibility, tolerability, safety and efficacy of
      using a new surgical technique for the repair of anterior urethral strictures to
      preserve vascular supply to the urethra and its entire muscular and neurogenic
      support. PATIENTS AND METHODS: In all, 24 patients (mean age 46 years) underwent
      a new one-sided anterior dorsal oral mucosal graft urethroplasty while preserving
      the lateral vascular supply to the urethra, the central tendon of the perineum,
      the bulbospongiosum muscle and its perineal innervation. The cause of stricture
      was instrumentation in three cases (12%), unknown in five (21%), infection in
      four (17%), and lichen sclerosus in 12 (50%). The stricture site was bulbar in 12
      cases (50%) and panurethral in 12 (50%). The mean stricture length was 4.2 cm in
      patients with bulbar strictures and 10 cm in patients with panurethral
      strictures. Of 24 patients, 20 patients (83%) had received previous treatments.
      Clinical outcome was considered a failure when any postoperative instrumentation
      was needed, including dilatation. RESULTS: The overall mean (range) follow-up was
      22 (12-55) months. Of the 24 patients, 22 (92%) had a successful outcome and two
      (8%) were failures. One failure was treated using definitive perineal
      urethrostomy and another failure underwent successful internal urethrotomy.
      CONCLUSIONS: The preservation of the one-sided vascular supply to the urethra and
      its entire muscular and neurogenic support should represent a slight but
      significant step toward perfecting the surgical technique of urethral
      reconstruction using a minimally invasive approach.

PMID- 19388991
TI  - Robot-assisted laparoscopic prostatectomy is not associated with early
      postoperative radiation therapy.
AB  - OBJECTIVE: To compare open radical prostatectomy (RP) and robot-assisted
      laparoscopic prostatectomy (RALP), and to determine whether RALP is associated
      with a higher risk of features that determine recommendations for postoperative
      radiation therapy (RT). PATIENTS AND METHODS: Patients undergoing RP from 2003 to
      2007 were stratified into two groups: open RP and RALP. Preoperative (PSA level,
      T stage and Gleason score), pathological factors (T stage, Gleason score,
      extracapsular extension [ECE] and the status of surgical margins and seminal
      vesicle invasion [SVI]) and early treatment with RT or referral for RT within 6
      months were compared between the groups. Multivariate analysis was used to
      control for selection bias in the RALP group. RESULTS: In all, 904 patients were
      identified; 368 underwent RALP and 536 underwent open RP (retropubic or
      perineal). Patients undergoing open RP had a higher pathological stage with ECE
      present in 24.8% vs 19.3% in RALP (P = 0.05) and SVI in 10.3% vs 3.8% (P <
      0.001). In the RALP vs open RP group, there were positive surgical margins in
      31.5% vs 31.9% (P = 0.9) and there were postoperative PSA levels of (3) 0.2 ng/mL
      in 5.7% vs 6.3% (P = 0.7), respectively. On multivariate analysis to control for
      selection bias, RALP was not associated with indication for RT (odds ratio (OR)
      1.10, P = 0.55), or referral for RT (OR 1.04, P = 0.86). CONCLUSION: RALP was not
      associated with an increase in either indication or referral for early
      postoperative RT.

PMID- 19388992
TI  - Receptor-induced phasic activity of newborn mouse bladders is inhibited by
      protein kinase C and involves T-type Ca2+ channels.
AB  - OBJECTIVE: To investigate the mechanisms involved in the phasic contractile
      activity after muscarinic receptor activation of newborn urinary bladders and to
      compare neonatal and adult bladders. MATERIALS AND METHODS: Detrusor muscle
      strips were isolated from newborn mice (aged 0-2 days) and compared with
      preparations from adult mice (aged 10-12 weeks). The effects of an activator
      (phorbol 12,13-dibutyrate, PDBu) and an inhibitor (GF109203X) of protein kinase C
      (PKC) on contractions were investigated. T-type Ca2+ channels were blocked with
      NiCl2. RESULTS: The newborn urinary bladders responded with prominent phasic
      contractile activity in response to carbachol (1 microM). GF109203X (3 microM)
      reduced carbachol-induced force by approximately 60% in the newborn, compared
      with 30% in the adult. PDBu (1 microM) enhanced the muscarinic receptor-mediated
      contraction in adult bladder muscle, whereas it completely abolished the
      responses in the newborn. There was no inhibition after activation with
      depolarization (high-K+) or purinergic agonists (ATP, alpha,beta-methylene ATP).
      NiCl2 (>30 microM) inhibited the peak responses to carbachol in the newborn and
      at 300 microm it completely abolished the phasic contractile response. The
      responses of the adult bladder muscle were only marginally affected by NiCl2.
      CONCLUSIONS: Muscarinic receptor stimulation recruits the PKC signalling pathway
      in both the adult and neonatal urinary bladder. Potent PKC activation is
      inhibitory on carbachol-induced activation in the newborn and stimulatory in the
      adult bladder. Furthermore, muscarinic receptor stimulation activates T-type Ca2+
      channels in the newborn, but not the adult bladder.

PMID- 19388993
TI  - Renal cell carcinoma with inferior vena caval extention: impact of tumour extent
      on surgical outcome.
AB  - OBJECTIVE: To evaluate our experience with surgical resection of renal cell
      carcinoma (RCC) with inferior vena cava (IVC) involvement and examine the
      relationship between prognosis and tumour extent. PATIENTS AND METHODS: A
      retrospective review of nephrectomy performed between 1985 and 2005 identified 50
      patients presenting with tumour thrombus extension into the IVC. Clinical
      characteristics and outcome were evaluated. RESULTS: Of the 50 patients
      evaluated, 7, 26, 10 and 7 presented with level I, II, III and IV thrombus,
      respectively. Major postoperative complications occurred in 16% of patients.
      Local or distant failure occurred in 25 (64%) patients. The mean time to
      recurrence was 10 months. Only supra-diaphragmatic extension of the tumour
      thrombus was predictive of disease recurrence. CONCLUSION: Locally advanced RCC
      with IVC thrombus remains associated with significant local and distant failure
      rate. The level of thrombus extension is significantly associated with disease
      recurrence. Effective adjuvant therapy is needed to improve outcome in this
      patient population.

PMID- 19388994
TI  - Comparison between a serous-lined extramural tunnel and T-limb ileal procedure as
      an antireflux technique in orthotopic ileal substitutes: a prospective randomized
      trial.
AB  - OBJECTIVE: To compare the functional results from a prospective randomized trial
      of two different reflux-prevention techniques for ileal bladder substitution.
      PATIENTS AND METHODS: In all, 60 patients with invasive bladder cancer were
      randomized to receive either a serous-lined extramural tunnel (group 1) or T-limb
      ileal procedure (group 2) as an antireflux technique for the ileal substitute.
      The preoperative evaluation included intravenous urography, radioisotope
      renography to evaluate glomerular filtration rates (GFRs) and renal cortical
      imaging with 99mTc- dimercaptosuccinic acid to assess parenchymal scarring.
      Evaluable patients were re-assessed by the same imaging, and by ascending
      studies. RESULTS: The follow-up included 27 patients (49 units) in group 1 and 23
      (45 units) in group 2, with a mean (sd) follow-up of 6.3 (0.5) and 7.4 (1.9),
      respectively. Uretero-ileal strictures were diagnosed in one renal unit in each
      group (P = 0.5). Ascending studies showed no reflux in any patients in group 1,
      while 13 renal units (29%) in group 2 were refluxing (P < 0.01). There was
      progressive cortical scarring with or with no significant reduction in GFR (>25%)
      in three and four renal units in groups 1 and 2, respectively. Among the 13
      refluxing units in group 2, three showed a significant deterioration in GFR and
      one renal unit was diagnosed with progressive cortical scarring. CONCLUSION: Both
      procedures provided a low rate of anastomotic stricture, with acceptable
      preservation of renal function. The serous-lined extramural tunnel provided a
      more effective antireflux mechanism.

PMID- 19388995
TI  - Precursor of prostate-specific antigen expression in prostatic intraepithelial
      neoplasia and adenocarcinoma: a study of 90 cases.
AB  - OBJECTIVE: To assess the expression of the precursor of prostate-specific antigen
      (pro-PSA), a distinct molecular form of serum-free PSA that includes native and
      truncated forms, in benign epithelium, high-grade prostatic intraepithelial
      neoplasia (PIN) and prostatic adenocarcinoma. MATERIALS AND METHODS: We
      immunohistochemically evaluated 90 formalin-fixed, paraffin-embedded prostate
      needle biopsies using monoclonal antibodies against [-2] pro-PSA, native [-5/-7]
      pro-PSA, prostate-specific membrane antigen (PSMA), PSA and racemase. Staining
      intensity was recorded using a scale of 0-3 (0, no staining; 3, highest
      staining). The percentage of immunoreactive cells in benign epithelium, high
      grade PIN and adenocarcinoma was estimated in increments of 10%. RESULTS: All
      cases had [-5/-7] pro-PSA immunoreactivity. There was weak focal perinuclear
      cytoplasmic immunoreactivity for [-5/-7] pro-PSA in 62% (range 0-90%) of benign
      epithelial cells, whereas there was strong diffuse cytoplasmic staining in 83%
      (range 10-90%) of high-grade PIN and 87% (range 40-90%) of cancer cells. Almost
      all (99%) cases were immunoreactive for [-2] pro-PSA. The median (range)
      proportion of cells expressing [-2] pro-PSA was lower in benign epithelium, at 17
      (0-80)%, than in high-grade PIN, at 55 (0-90)% (P < 0.001) and adenocarcinoma, at
      55 (0-100)% (P < 0.001). The intensity of immunoreactivity for both isoforms
      increased from benign to neoplastic (high-grade PIN and adenocarcinoma)
      epithelium. A total of 31% of high-grade PIN and 11% of cancer cases with
      negative racemase staining showed strong staining for [-5/-7] pro-PSA.
      CONCLUSION: The expression of [-5/-7] pro-PSA in benign and neoplastic cells
      might be used in combination with high molecular weight keratin, p63, and
      racemase to distinguish benign epithelium from high-grade PIN and adenocarcinoma,
      particularly when racemase staining is negative. Both isoforms are sensitive
      markers for prostatic epithelium, making them possible candidates for
      investigating carcinoma with an unknown primary, particularly in cases in which
      PSA staining is negative and the level of suspicion is high.

PMID- 19388996
TI  - Listening to the patient: a flexible approach to the use of antimuscarinic agents
      in overactive bladder syndrome.
AB  - Several studies with modern antimuscarinics have used a flexible-dosing strategy.
      We reviewed data from several studies with solifenacin, darifenacin and
      oxybutynin extended-release that evaluated the impact of dose flexibility on
      clinical management. A strategy based on patient-requested dose increases was
      found to be consistently effective in improving the symptoms of overactive
      bladder. Patients requesting a dose increase often had more severe symptoms at
      baseline than those who did not request a dose increase, and these patients
      derived most benefit from the increased dose. Specialists and family doctors
      should encourage open discussion with their patients about requesting dose
      titration so as to meet patients' individual needs.

PMID- 19388997
TI  - Paediatric testicular cancer: an updated review of incidence and conditional
      survival from the Surveillance, Epidemiology and End Results database.
AB  - OBJECTIVES: To determine, using the Surveillance, Epidemiology, and End Results
      (SEER) population-based database, the epidemiological variables and update the
      understanding of testicular tumours in children, as knowledge of their incidence
      and survival is predicated upon multi-institutional cooperation. PATIENTS AND
      METHODS: Using the SEER database, we ascertained the incidence rate, 5-year
      survival by disease stage at diagnosis, and 5-year conditional survival after
      surviving for 1-3 years for cases recorded between 1973 and 2005. We stratified
      the incidence rate by race and histology to examine if these factors affect
      disease characteristics. RESULTS: We identified 195 cases of testicular tumours
      in children from birth to age 14 years, and 785 for children aged 15-18 years.
      Yolk sac tumour was the most common testicular tumour, and overall, Caucasian
      children were most at risk and four times more likely to be affected than African
      American children. The incidence rate of testicular tumour overall has not
      increased significantly since 1973. Conditional survival is excellent for all
      testicular malignancies, with a 1-year conditional survival (chance of surviving
      5-years after having survived the first year) of 99.6%. CONCLUSIONS: We present
      an updated analysis of the SEER database for the incidence and survival of
      testicular tumours, and revisit the issue of whether the incidence of testicular
      tumours in children is increasing. We also present to our knowledge, the first
      calculation of conditional survival in children for this malignancy. There has
      been no significant increase in the incidence of testicular tumours for children
      aged <14 years. By contrast, the postpubertal group aged 15-18 years showed a
      reversal in this trend.

PMID- 19388998
TI  - A contemporary standard for morbidity and outcome after radical cystectomy.
AB  - OBJECTIVE: To report the temporal changes in peri-operative outcome over an
      extended period in patients undergoing radical cystectomy (RC) for all causes,
      irrespective of the previous treatment or pathology; and to establish a current
      standard of peri-operative outcome for RC by analysis of contemporary operative
      mortality rates (2000-5) factored for risk factors that might predict outcome.
      PATIENTS AND METHODS: All patients undergoing RC between 1970 and 2005 were
      analysed; this was an unselected single-centre series and included patients
      previously treated by definitive radiotherapy, chemotherapy, and cases of RC
      where the primary tumour involved the bladder but was not of bladder origin.
      RESULTS: In all, 846 patients had a RC, of whom 647 had a bladder primary tumour
      and 199 a primary tumour elsewhere (gynaecological, colorectal and others). There
      was a progressive reduction in 30- and 60-day mortality rates, such that the
      current peri-operative mortality (1999-2005) was 0.4% and 2.6%, respectively.
      There was a significant reduction in the re-operation rate over the decades
      (P=0.01), which is currently 4.7%. Patient age was a significant factor in 30-
      and 60-day mortality rates (P<0.001 for both) but there was no significant
      association between either American Society of Anesthesiologists grade or T stage
      with complication rates (P=0.61 and 0.12, respectively). CONCLUSION: There has
      been a progressive reduction in mortality related to RC, associated with both
      cases of RC and pelvic exenteration. The contemporary standard for 30-and 60-day
      mortality rates for these operations is 0.4% and 2.6%, respectively.

PMID- 19388999
TI  - The role of 'notch' in urological cancers.

PMID- 19389000
TI  - What would truly patient-centred urological care look like?

PMID- 19389001
TI  - The effect of endothelin-1 on the production of interleukin-6 in cultured human
      detrusor smooth muscle cells, and the effect of interleukin-6 on the contractile
      response of bladder smooth muscle strips from rats.
AB  - OBJECTIVE: To determine the effect of endothelin-1 (ET-1) on the production of
      interleukin-6 (IL-6) in cultured human detrusor smooth muscle cells (HDSMCs) and
      the effect of IL-6 on the contractile response of bladder smooth muscle strips
      from rats. MATERIALS AND METHODS: The expression of IL-6 mRNA and production of
      IL-6 protein in cultured HDSMCs treated with the different concentrations of ET-1
      were assayed by reverse transcriptase-polymerase chain reaction and specific
      enzyme-linked immunosorbent assay, respectively. The strips from Sprague-Dawley
      rats were either untreated or treated with 1 ng/mL of IL-6 for 60 min. Using
      increasing cumulative concentrations of acetylcholine (ACh), bethanechol (BCh),
      or sodium nitroprusside, we assessed the concentration-contraction or the
      relaxation responses. In cystitis-induced strips, change of contractions induced
      by noradrenaline (NA) with or without treatment of IL-6 were assessed. The IL-6
      treated strips were incubated for 30 min in the presence or absence indomethacin
      or SQ29548, and then the effects on ACh- or BCh-induced contractions were
      measured. RESULTS: The expression of IL-6 mRNA and the production of IL-6 protein
      on the cultured HDSMCs pretreated by ET-1 were significantly higher than in the
      control (P<0.05). The ACh- and BCh-induced contractions were increased in the IL
      6 pretreated strips from both dome and trigone, regardless of the presence of
      urothelium (P<0.05). The presence of cystitis augmented the NA-induced
      contractions (P<0.05). The contractions induced by ACh and BCh were inhibited by
      indomethacin and SQ29548. CONCLUSIONS: ET-1 induces expression of IL-6 mRNA and
      production of IL-6 protein on HDSMCs. IL-6 enhances detrusor smooth muscle
      contractility via the muscarinic or adrenergic receptor pathway.

PMID- 19389002
TI  - The number of procedures required to achieve optimal competency with male
      circumcision: findings from a randomized trial in Rakai, Uganda.
AB  - OBJECTIVE: To assess the number of procedures required to achieve optimal
      competency (time required for surgery with minimal adverse events) in Rakai,
      Uganda, and thus facilitate the development of guidelines for training providers,
      as male circumcision reduces the acquisition of human immunodeficiency virus
      (HIV) in men and is recommended for HIV prevention. PATIENTS AND METHODS: In a
      randomized trial, 3011 men were circumcised, using the sleeve method, by six
      physicians who had completed training, which included 15-20 supervised
      procedures. The duration of surgery from local anaesthesia to wound closure,
      moderate or severe surgery-related adverse events (AEs), and wound healing were
      assessed in relation to the number of procedures done by each physician. RESULTS:
      The median age of the patients was 24 years. The number of procedures per surgeon
      was 20-981. The mean time required to complete surgery was approximately 40 min
      for the first 100 procedures and declined to 25 min for the subsequent 100
      circumcisions. After controlling for the number of procedures there was no
      significant difference in duration of the surgery by patient HIV status or age.
      The rate of moderate and severe AEs was 8.8% (10/114) for the first 19
      unsupervised procedures after training, 4.0% for the next 20-99 (13/328) and 2.0%
      for the last 100 (P for trend, 0.003). All AEs resolved with management.
      CONCLUSION: The completion of more than 100 circumcisions was required before
      newly trained physicians achieved the optimum duration of surgery. AEs were
      higher immediately after training and additional supervision is needed for at
      least the first 20 procedures after completing training.

PMID- 19389003
TI  - Longitudinal studies of time-dependent changes in both bladder and erectile
      function after streptozotocin-induced diabetes in Fischer 344 male rats.
AB  - OBJECTIVES: To provide sensitive physiological endpoints for the onset and long
      term progression of deficits induced by diabetes mellitus (DM) in bladder and
      erectile function in male rats, and to evaluate parallel changes in urogenital
      and nerve function induced by hyperglycaemia over a protracted period as a model
      for chronic deficits in patients with diabetes. MATERIALS AND METHODS: The study
      comprised in 877 male, 3-month-old, Fischer 344 rats; 666 were injected
      intraperitoneally with 35 mg/kg streptozotocin (STZ) and divided into insulin
      treated and untreated diabetic groups. The rats were studied over 8 months and
      measurements made of both erectile and bladder function, as well as nerve
      conduction studies over the duration of the study. RESULTS: There was an early
      (first month) abnormality of both erectile and bladder function that persisted
      through the 8 months of the study. The erectile dysfunction was manifest as
      reduced intracavernous pressure/blood pressure ratio, and the bladder dysfunction
      as a persistent increase in detrusor overactivity with no detrusor
      decompensation. Insulin treatment prevented or modified the abnormality in each
      organ. Hyperglycaemia caused a progressive decrease in caudal nerve conduction
      velocity. The mean digital sensory and tibial motor nerve conduction velocity did
      not deteriorate over time. Correlation measurements of nerve and organ function
      were not consistent. CONCLUSIONS: The results of this extensive long-term study
      show early and profound effects of hyperglycaemia on the smooth muscle of the
      penis and bladder, that were persistent and stable in surviving rats over the 8
      months. The physiological changes did not correlate well with neurological
      measurements of those organs. Significantly, diverse smooth-muscle cellular and
      subcellular events antedated the measured neurological manifestations of the
      hyperglycaemia by several months. Although autonomic diabetic neuropathy is a
      primary life-threatening complication of long-term diabetes in humans, this rat
      model of STZ-induced diabetes showed that the rapid onset of physiological
      manifestations was based on many molecular changes in the smooth muscle cells in
      this model of type 1 DM.

PMID- 19389004
TI  - Safety and efficacy of sildenafil citrate in treating erectile dysfunction in
      patients with combat-related post-traumatic stress disorder: a double-blind,
      randomized and placebo-controlled study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of sildenafil citrate for treating
      erectile dysfunction (ED) in patients with combat-related post-traumatic stress
      disorder (PTSD). PATIENTS AND METHODS: In all, 266 combat-exposed war veterans
      with ED (aged 37-59 years) were recruited. They met the Diagnostic and
      Statistical Manual of Mental Disorders-IV criteria for PTSD according to the
      Structured Clinical Interview for Patients, Investigator Version. The patients
      were also evaluated with the Clinician-Administered PTSD Scale, both to establish
      the diagnosis of PTSD and to measure symptom severity. Only patients with
      psychogenic ED were included in the study. Patients with comorbid conditions
      (diabetes mellitus, hypercholesterolaemia, hypertension, Peyronie's disease) and
      smokers of more than five cigarettes daily were excluded. The patients were
      randomly divided into a group of 133 who received 100 mg of on-demand sildenafil
      0.75-2 h before sexual stimulation, and 133 who received placebo. Patients were
      asked to use > or =16 doses or attempts at home. The efficacy of the treatments
      was assessed every four attempts during treatment, and at the end of the study,
      using responses to the 15-question International Index of Erectile Function
      (IIEF), Sexual Encounter Profile diary questions 2 and 3, Erectile Dysfunction
      Inventory of Treatment Satisfaction questionnaire, patients' event logs of sexual
      activity, and a Global Assessment Question about erections. RESULTS: Sildenafil
      did not produce significantly and substantially greater improvement than placebo
      in each of the primary and secondary outcome measures (P = 0.08). A normal EF
      domain score (> or =26) at endpoint was reported by 13 (9.8%), and 11 (8.3%) of
      patients on the sildenafil and placebo regimens, respectively (P = 0.09).
      Patients treated with sildenafil had no statistically significantly greater
      improvement in the five sexual function domains of the IIEF questionnaire than
      those treated with placebo (P = 0.08). The incidences of treatment-emergent
      adverse events were significantly greater in the sildenafil arm than in the
      placebo group (P = 0.01). CONCLUSIONS: Sildenafil is no better than placebo in
      treating PTSD-emergent ED. Further randomized clinical trials are warranted in
      combat veterans and other populations with PTSD to better elucidate the role of
      phosphodiesterase type 5 inhibitors in treating PTSD-emergent ED.

PMID- 19389005
TI  - Vitamin D repletion does not alter urinary calcium excretion in healthy
      postmenopausal women.
AB  - OBJECTIVE: To evaluate, in a posthoc analysis of a previous study, whether
      vitamin D repletion in postmenopausal women with insufficient vitamin D increases
      urinary calcium excretion, as vitamin D therapy might contribute to
      hypercalciuria and calcium stones in susceptible individuals, and the effect of
      vitamin D on the risk of urolithiasis warrants attention. SUBJECTS AND METHODS:
      We recruited 18 women at > or =5 years after menopause who had vitamin D
      insufficiency (serum 25(OH)-vitamin D, 16-24 mg/dL). We excluded women with a
      history of urolithiasis and kidney disease. Women had one calcium absorption
      study when vitamin D-insufficient, received vitamin D therapy, and completed a
      second calcium absorption study when vitamin D-replete. We fed subjects meals
      that mirrored the nutrient composition from self-reported 7-day diet diaries. To
      measure calcium absorption, we collected urine for 24 h during both visits.
      RESULTS: We achieved vitamin D repletion in all women (25(OH)-vitamin D before
      and after treatment, 22 and 63 mg/dL, respectively; P < 0.001). The mean calcium
      intake was 832 mg/day. Residual urine specimens were available for 16 women,
      allowing a measurement of 24-h urinary calcium. Calcium excretion did not change
      after vitamin D therapy (212 before vs 195 mg/day after; P = 0.60). Of four women
      with hypercalciuria (>247 mg/day), calcium excretion decreased in three (377-312
      mg/day, not significant). CONCLUSION: Vitamin D supplementation did not increase
      the urinary calcium excretion in healthy postmenopausal women. Many stone formers
      are at risk of premature bone loss, vitamin D insufficiency, or both. Based on
      the present results we suggest a study of patients with hypercalciuria and
      nephrolithiasis to determine the risks of vitamin D therapy.

PMID- 19389006
TI  - Outcomes of patients undergoing radical cystoprostatectomy for bladder cancer
      with prostatic involvement on final pathology.
AB  - OBJECTIVE: To evaluate the impact of prostatic urothelial carcinoma (PUC) on
      survival of patients with bladder cancer undergoing radical cystoprostatectomy
      (RCP). PATIENTS AND METHODS: From 1998 to 2005, 463 consecutive RCPs were
      performed for UC of the bladder. Patients with PUC at final pathology were
      grouped by route of prostatic invasion (bladder origin or prostatic urethral
      origin) and by depth of invasion (carcinoma in situ, ductal invasion, and stromal
      invasion). Univariate and multivariate survival analyses were performed. RESULTS:
      In all, 35% (162/463) of patients had PUC. The 3-year overall survival (OS) was
      58.2% for patients who did not have PUC, 59.2%, 51.7%, and 16.8% in order of
      increasing depth of prostatic invasion for patients with PUC of urethral origin,
      and 6.7% for patients with bladder-origin PUC. Survival differed significantly
      between stromal and non-stromal PUC (P < 0.001). Patients with PUC of bladder
      origin had a higher rate of positive lymph nodes (LNs) than patients with stromal
      PUC of prostate origin (74.3% vs 27.8%, P < 0.001), but survival was similar (P =
      0.619). On multivariate analysis, age (P = 0.035), increasing bladder stage (P =
      0.003), stromal invasion (P = 0.002) and positive LNs (P < 0.001) were predictors
      of poor OS. CONCLUSION: Depth of prostatic invasion correlates with outcome.
      While prostatic involvement originating in the bladder is associated with higher
      rates of positive LNs, survival is similar to patients with stromal involvement
      of urethral origin. Age, bladder tumour stage, prostatic stromal involvement and
      positive LNs predict adverse outcome. Our data support separate staging of the
      prostate in RCP specimens.

PMID- 19389007
TI  - Differences among patients undergoing perineal or retropubic radical
      prostatectomy in pain and perioperative variables: a prospective study.
AB  - OBJECTIVE: To compare pain in the first 24 h, the perioperative variables and the
      histopathological results among patients who had perineal (PRP) and retropubic
      radical prostatectomy (RRP), in a randomized trial. PATIENTS AND METHODS:
      Patients with localized prostate cancer were accrued after selection using
      inclusion and exclusion criteria; they were prospectively randomized into four
      different groups: P1 (PRP with general anaesthesia), P2 (RPP with general plus
      epidural anaesthesia), R1 (RRP with general anaesthesia), and R2 (RRP with
      general plus epidural anaesthesia) and data collected for age, body mass index,
      prostate weight, serum prostate-specific antigen level, Gleason score and
      clinical stage. Pain after RP was evaluated using numerical and oral scales, and
      by morphine intake delivered by a patient-controlled analgesia pump.
      Perioperative features assessed prospectively were operating time, intraoperative
      bleeding, time to diet, time to ambulation, hospital stay and complications.
      Immediate oncological results were assessed based on histopathological
      evaluation, e.g. Gleason score, tumour volume, prostate volume, surgical margins
      and final pathological stage. RESULTS: Between October 2004 and October 2007 80
      patients were accrued (mean age 63 years, range 42-80). The groups were similar
      for preoperative data, but group R1 had larger prostates (P = 0.001). For
      postoperative pain, group R1 had a significantly greater intensity of pain, based
      on the visual analogue scales, and greater morphine intake during the first 24 h
      than the other three groups. Groups P1 and P2 had significantly less bleeding
      (511 and 612 mL) than groups R1 and R2 (926 and 1165 mL; P < 0.001), regardless
      of both prostate size and anaesthesia. Complications occurred in 27.5% and 25%
      (not significant) of patients after PRP and RRP, respectively. There were no
      differences in positive surgical margin rate and histopathological evaluation
      among the groups. CONCLUSIONS: Patients who had RRP with general anaesthesia had
      a greater intensity of pain and higher morphine intake than the other groups. Men
      who had PRP had significantly less bleeding and shorter hospital stay than those
      having RRP.

PMID- 19389008
TI  - Impact of ethnicity on surgical margins at radical prostatectomy.
AB  - OBJECTIVE: To determine if the rate of positive surgical margins (PSMs), and in
      particular apical PSMs, at radical prostatectomy (RP) for prostate cancer, is
      higher in African-American (AA) than Caucasian men, given their often narrower
      and deeper pelvis. PATIENTS AND METHODS: From 1999 to 2007, 3145 consecutive
      patients underwent RP, either open retropubic (RRP) or laparoscopic (LRP), with
      no previous treatment, by one of five surgeons. Multivariate logistic regression
      was used to determine the effect of ethnicity (AA vs Caucasian) on overall and
      site-specific PSMs, adjusting for age, body mass index, RP approach (RRP vs LRP),
      surgeon, surgeon case number, year of surgery, preoperative serum prostate
      specific antigen level, specimen weight, estimated blood loss, pathological organ
      confined status, and pathological Gleason score. RESULTS: In all, 205 men were AA
      and 2940 Caucasian; PSMs were identified in 376 (12.0%) men, 35 (17.1%) in AA and
      341 (11.6%) in Caucasian men. PSMs were identified at the apex in 148 (4.7%), the
      bladder neck in 29 (0.9%), posteriorly in 169 (5.4%), and anteriorly in 78 (2.5%)
      men. For apical PSM, ethnicity was a significant predictor, with an odds ratio of
      1.76 (95% confidence interval 1.01-3.04, P = 0.045) for AA vs Caucasian,
      independent of pathological organ-confined status and PSA level. Ethnicity was
      not a significant independent predictor of overall PSMs or PSMs at other sites
      (bladder neck, posteriorly, or anteriorly). CONCLUSIONS: The rate of apical PSMs,
      but not overall PSMs, at RP was higher in AA than Caucasian men, controlling for
      other covariates. Further investigation is necessary to determine if pelvic shape
      is responsible for this observation.

PMID- 19389009
TI  - Tumour length of the largest focus predicts prostate-specific antigen-based
      recurrence after radical prostatectomy in clinically localized prostate cancer.
AB  - OBJECTIVE: To investigate the possible significance of tumour dimensional
      variables, including maximum tumour diameter (MTD), maximum tumour area (MTA) and
      total tumour volume (TTV), with standard prognostic factors for predicting
      prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP).
      PATIENTS AND METHODS: Serial whole sections of the prostate from 164 patients who
      had RP for localized prostate cancer were investigated. Cox proportional hazards
      regression models were used for univariate and multivariate analyses to test the
      relationships between biochemical failure and clinicopathological factors,
      including tumour dimensional variables. The results were analysed retrospectively
      to develop a prognostic factor-based model for risk stratification. RESULTS: In
      the univariate Cox proportional hazard model, pathological T stage, Gleason
      score, perineural invasion, microvascular invasion, positive surgical margins,
      MTD, MTA and TTV were significantly associated with biochemical failure. In the
      multivariate Cox proportional hazard model using a stepwise inclusion of these
      factors, Gleason score, positive surgical margins and MTD were independent
      indices in association with biochemical failure. Using the three statistically
      significant variables, the relative risk of biochemical failure could be
      calculated. CONCLUSION: These results imply that MTD is possibly one of the most
      important prognostic factors for predicting biochemical recurrence after RP. As
      calculating the MTD on the section a rapid, simple and objective method, it can
      be used instead of the TTV calculation. The prognostic factor- based risk
      stratification might help clinicians to predict biochemical failure after RP.

PMID- 19389010
TI  - Xanthogranulomatous pyelonephritis: presentation and management in the era of
      laparoscopy.
AB  - OBJECTIVE: To report a contemporary series of patients with xanthogranulomatous
      pyelonephritis (XGP, an inflammatory condition of the kidney that has
      traditionally been treated with open nephrectomy, ON), managed with either ON or
      laparoscopic nephrectomy (LN), as early reports suggest that the benefits of LN
      do not extend to patients with XGP. PATIENTS AND METHODS: The medical and
      procedural records of patients with pathologically confirmed XGP between December
      1993 to February 2004 were reviewed retrospectively. During this period, 26
      patients (mean age 43.5 years, range 17-85) had surgical management of XGP;
      information on the mode of presentation, surgical management, hospital course and
      complications were analysed. RESULTS: Twelve (46%) and 14 (54%) patients had ON
      and LN, respectively. The LN group had significantly lower blood loss (P =
      0.002), transfusion rates (P = 0.02), time to resumption of oral intake (P =
      0.002) and length of hospital stay (P = 0.002) than the ON group. One (7%) LN was
      converted to ON due to failure to progress. The overall complication rates
      between the ON and LN groups were not significantly different (P = 0.95).
      CONCLUSIONS: LN in the setting of XGP is often difficult and requires advanced
      laparoscopic skills. In highly selected patients this approach can be offered,
      with acceptable morbidity, allowing for lower blood loss and shorter convalesce
      times.

PMID- 19389011
TI  - Bladder neck contracture after radical retropubic prostatectomy using an
      intussuscepted vesico-urethral anastomosis: incidence with long-term follow-up.
AB  - OBJECTIVE: To evaluate the incidence of bladder neck contracture (BNC), a known
      complication of radical retropubic prostatectomy (RRP), after a 9-year experience
      by one surgeon using a novel approach to lower urinary tract reconstruction, the
      intussuscepted vesico-urethral anastomosis (IVUA). PATIENTS AND METHODS: After
      institutional review board approval, the charts of 406 patients who had RRP for
      clinically localized prostate cancer from March 1998 to July 2007 were reviewed
      retrospectively. All patients had lower urinary tract reconstruction using the
      IVUA technique, which involves a looped urethral suture using six double-armed
      sutures that are drawn 'inside-to-out' from staggered points on the urethral
      stump through the bladder neck opening. When the sutures are tied down, the
      urethra is intussuscepted into the bladder neck opening. RESULTS: At a median
      follow-up of 48 months, three patients developed BNC: one was at increased risk
      secondary to a previous TURP; one had his catheter removed on the second day
      after RRP in the presence of a suprapubic tube and developed a BNC at his 'dry'
      anastomosis; and one with no risk factors developed a BNC. Balloon dilatation,
      laser incision and self obturation were successful in stabilizing the strictures
      while preserving continence. Overall, the incidence of BNC in this series was
      three of 406 (0.74%). CONCLUSIONS: IVUA gives a lower incidence of BNC over a
      long-term follow-up than rates cited in previous reports. IVUA is a valuable
      technique for lower urinary tract reconstruction in patients undergoing RRP.

PMID- 19389012
TI  - A single-institution experience with induction and maintenance intravesical
      docetaxel in the management of non-muscle-invasive bladder cancer refractory to
      bacille Calmette-Guerin therapy.
AB  - OBJECTIVE: To analyse the durability of response for patients with non-muscle
      invasive bladder cancer (NMIBC) refractory to bacille Calmette-Guerin (BCG)
      therapy and treated with intravesical docetaxel in a combined induction and
      maintenance regimen. PATIENTS AND METHODS: A previous phase I trial showed
      docetaxel to be safe for intravesical therapy, with no systemic absorption and
      minimal toxicity after six weekly instillations for patients with BCG-refractory
      NMIBC. In that trial, docetaxel gave a 56% complete response (CR) rate at 12
      weeks, but the durability was only 22%. Thus a second group of patients was
      treated with a 6-week induction and then given monthly maintenance therapy with
      intravesical docetaxel. Thirteen patients with BCG-refractory Ta, T1, or Tis
      transitional cell carcinoma were treated. Induction therapy was administered as
      six weekly intravesical instillations of 75 mg followed by single-dose monthly
      maintenance therapy for nine additional instillations in patients who had a CR.
      The initial response at 12 weeks from the start of induction therapy was
      evaluated by cystoscopy with biopsy, and urine cytology. The follow-up consisted
      of quarterly cystoscopy with biopsy and cytology, and periodic imaging. RESULTS:
      The median follow-up was 13 months; 10 of 13 patients had a CR after induction,
      and six have remained disease-free during the follow-up. Of those in who the
      treatment failed, six had transurethral resection of the tumour and one a
      cystectomy. All 10 initial responders completed at least three instillations of
      maintenance therapy to date (median nine instillations), of whom six have
      remained recurrence-free. CONCLUSION: Monthly maintenance therapy with
      intravesical docetaxel appears to extend the durability of response to induction
      treatment for a selected group of patients with BCG-refractory NMIBC, and might
      decrease the overall risk of recurrence in high-risk NMIBC.

PMID- 19389013
TI  - Activation of the mammalian target of rapamycin signalling pathway in prostate
      cancer and its association with patient clinicopathological characteristics.
AB  - OBJECTIVE: To evaluate the activation level of the mammalian target of rapamycin
      (mTOR) signalling pathway in Chinese patients with prostate cancer, as this
      pathway is over-activated in many human cancers and is an attractive target for
      cancer therapy. PATIENTS AND METHODS: We used immunohistochemistry to investigate
      the activation level of five important markers of the mTOR pathway, including
      PTEN, p-Akt, p-mTOR, p-p70S6K and p-4E-BP1, in tissues from 182 patients with
      prostate cancer, 20 with benign prostatic hyperplasia (BPH) and 10 with high
      grade prostatic intraepithelial neoplasia (HGPIN). The expression levels of these
      five markers were associated with patient clinical and pathological
      characteristics. RESULTS: Expression levels of p-Akt, p-mTOR, p-4E-BP1 and p
      p70S6K were significantly higher in prostate cancer tissues than in BPH and HGPIN
      tissues. In 182 patients with prostate cancer the p-mTOR expression level
      significantly and positively correlated with its upstream p-Akt and downstream p
      4E-BP1 and p-p70S6K expression levels. The cancer Gleason score was significantly
      correlated with p-Akt and p-mTOR expression level but not with p-4E-BP1 and p
      p70S6K expression level. However, the p-4E-BP1 and p-p70S6K expression levels in
      primary cancer lesions were statistically significantly correlated with patient T
      stage and distant metastases. CONCLUSIONS: Most patients with prostate cancer
      have at least one component of the mTOR signalling pathway activated. The
      activation of the mTOR pathway might be involved in prostate cancer development
      and progression. The association between activation of mTOR pathway and patient
      clinicopathological variables suggested that not all patients are equally
      amenable to treatment strategies targeting the mTOR pathway.

PMID- 19389015
TI  - The long-term natural history of overactive bladder symptoms due to idiopathic
      detrusor overactivity in women.
AB  - OBJECTIVES: To assess the long-term natural history of overactive bladder (OAB)
      symptoms due to idiopathic detrusor overactivity (IDO) in women. PATIENTS AND
      METHODS: Original urodynamic traces were reviewed and women who were referred
      with OAB symptoms and found to have IDO on investigation in our urodynamic unit
      >=10 years previously were invited for a repeat urodynamic and symptomatic
      assessment. RESULTS: In all, 174 women were identified and invited to
      participate; 53 had repeat urodynamics, another 32 attended the unit for symptom
      assessment and a further 23 completed postal questionnaires. There were no
      significant symptomatic or urodynamic differences between these groups at
      baseline. Of the 53 who had repeat urodynamics, 46 (88%) had persistent
      symptomatic IDO. CONCLUSIONS: OAB symptoms have a significant effect on the
      quality of life of those affected. OAB symptoms due to IDO in women are
      persistent, lasting for >=10 years in 88% of this study population. This
      information might affect the treatment choices made by patients and their doctors
      in the management of this condition.

PMID- 19389014
TI  - Surgical management of adrenal cysts: single-institution experience.
AB  - OBJECTIVES: To assess the safety and efficacy of different surgical procedures
      used for managing benign adrenal cysts. PATIENTS AND METHODS: The files of 245
      patients presenting with adrenal masses was reviewed retrospectively; all had a
      thorough history taken and a physical examination. The radiological evaluation
      included abdominal plain X-rays, grey-scale abdominal ultrasonography and
      computed tomography with contrast medium. According to their clinical situation,
      patients had surgical open, laparoscopic intervention or were managed
      conservatively. The short- and long-term outcome of the open and laparoscopic
      techniques were evaluated. RESULTS: Twenty-six (11%) patients presented with
      adrenal cysts; the mean (sd, range) age at the time of presentation for adults
      was 41.4 (15, 17-82) years, while a 1-month female neonate and 1-year-old boy
      presented with an adrenal cyst. The mean (sd, range) size of the cysts was 10
      (3.5, 5-18) cm. Surgical intervention was the treatment of choice in 21 patients;
      11 (42%) had open adrenalectomy, while 10 (38%) had laparoscopic intervention.
      Both groups were comparable in the term of cyst size and operative time, while
      the laparoscopically managed group had a shorter hospital stay. Five patients
      were followed with no surgical intervention. At a mean follow-up of 90 months all
      patients were symptom free, with no radiological evidence of recurrence.
      CONCLUSIONS: Laparoscopic adrenalectomy is a safe and effective treatment for
      benign adrenal cysts. Compared with open techniques it has the advantages of a
      shorter hospital stay, less blood loss and enhanced cosmesis. Unlike aspiration
      of cyst contents, the recurrence of adrenal cysts after surgical removal is
      unlikely.

PMID- 19389016
TI  - Technical description and outcomes of a continuous anastomosis in open radical
      prostatectomy.
AB  - OBJECTIVE: To describe the surgical technique, objective and subjective medium
      term outcomes of a novel continuous vesico-urethral anastomotic suture in open
      radical prostatectomy (ORP). PATIENTS AND METHODS: A continuous anastomosis
      comprising separate anterior and posterior monofilament 3-0 polydioxanone
      sutures, with the bladder neck 'parachuted' down on to the urethral stump, was
      used in 39 consecutive patients. A cystogram was taken after ORP in the first 23
      patients. The catheter was removed as soon as patients were fully mobile. A
      validated postal questionnaire to determine continence and its effect on quality
      of life was sent to all patients >=3 months after ORP. RESULTS: The mean follow
      up was 18 months; there were no major complications. There was an insignificant
      or no leak in 91% of the patients who had a cystogram. Before discharge, 33
      patients reported that they were continent, whilst five required a pad(s) for
      stress incontinence, and one was discharged with a catheter after failing the
      first catheter removal. Of the 95% who completed the questionnaire, 95% either
      did not leak urine, or only leaked a small amount; 84% of patients reported that
      leaking had a minimal effect on everyday life. No patients developed symptomatic
      urethral or bladder neck stricture/contracture. CONCLUSIONS: Our technique of
      continuous anastomotic suturing for ORP is safe, reliable and well tolerated.
      Further randomized studies are warranted to compare the outcome with the standard
      interrupted vesico-urethral anastomosis.

PMID- 19389017
TI  - Ureteric response to abdominal radiotherapy and metallic double-pigtail ureteric
      stents: a pig model.
AB  - OBJECTIVE: To examine the safety and compatibility of full-length metal ureteric
      stents with abdominal radiotherapy. MATERIALS AND METHODS: Four ureteric stents
      (Resonance(TM), Cook Urological, Ireland) (RS) and four RSs specially modified to
      contain thermocouples were placed unilaterally in eight pigs. The contralateral
      ureters of the same pigs served as their controls, and contained two polymeric
      ureteric catheters and two similar specially modified to contain thermocouples,
      while the remaining four control ureters remained intact. All pigs were exposed
      to abdominal radiotherapy. The dose rate was approximately 5.3 Gy/min and a total
      radiation dose of 10 Gy was administered. Throughout the treatment the
      temperature was monitored by the RSs and catheters containing the thermocouples.
      The pigs were killed at 1 day (four), 7 days (two) and 15 days (two) after
      treatment, and all ureters examined histologically. RESULTS: There was no
      statistically significant increase in RS and catheter temperature throughout the
      treatment in any of the treated pigs (P > 0.05). All histological lesions
      reported were due to radiation treatment. There were no differences in histology
      between the ureters containing RSs and controls. CONCLUSION: RS usage is
      unrelated to any increase in stent temperature during abdominal radiotherapy and
      does not cause any further deterioration in the histology of the ipsilateral
      ureter, additional to that caused by the initial treatment.

PMID- 19389018
TI  - Nephrectomy improves survival in patients with invasion of adjacent viscera and
      absence of nodal metastases (stage T4N0 renal cell carcinoma).
AB  - OBJECTIVE: To examine the cancer-specific mortality (CSM) of patients with T4N0
      2M0 renal cell carcinoma (RCC) treated with either nephrectomy (RN) or no surgery
      (NS). PATIENTS AND METHODS: Of 43 143 patients with RCC identified in the
      Surveillance, Epidemiology and End Results database, 310 had tumours involving
      adjacent organs with no evidence of distant metastases (T4NanyM0) and had RN
      (246, 79.4%) or NS (64, 20.6%). Kaplan-Meier analyses, Cox regression and
      competing-risks regression models were used to compare the effect of RN vs NS on
      CSS. RESULTS: In patients with T4N0 disease the median survival benefit
      associated with RN vs NS was 42 months (48 vs 6 months, P < 0.001). Conversely,
      the median survival in patients T4N1-2 was no different between RN and NS (9.3 vs
      9.1 months, P = 0.9). Multivariable analyses in T4N0 cases indicated a
      substantial survival disadvantage for patients having NS vs RN (hazard ratio 4.8,
      P < 0.001). Conversely, in patients with N1-2 stages, the CSS was virtually the
      same for NS and RN (hazard ratio 0.9, P = 0.9). Competing-risks regression models
      confirmed the benefit of RC in patients with T4N0 and the lack of benefit in
      those with T4N1-2 disease, after controlling for other-cause mortality.
      CONCLUSION: Our data suggest a survival benefit in patients with T4N0 RCC treated
      with RC. By contrast, RN seems to have no effect on survival in patients with
      evidence of nodal metastases.

PMID- 19389019
TI  - Improvement in quality of life after botulinum toxin-A injections for idiopathic
      detrusor overactivity: results from a randomized double-blind placebo-controlled
      trial.
AB  - OBJECTIVE To determine whether botulinum toxin-A (BTX-A) treatment has an effect
      on the quality of life (QoL) of patients with overactive bladder (OAB) refractory
      to anticholinergics. PATIENTS AND METHODS This was a single centre, randomized,
      double-blind, placebo-controlled trial. Participants were men and women with
      idiopathic detrusor overactivity (IDO). Participants were randomised to receive
      either 200 U of BTX-A (Botox(R), Allergan Inc., Irvine, CA, USA; n = 16) or
      placebo (n = 18) via a trigone-sparing flexible cystoscopic technique. QoL was
      assessed using the King's Health Questionnaire (KHQ) at baseline and at 4 and 12
      weeks, after injection. At 12 weeks patients were 'unblinded' and a further open
      label follow-up in the BTX-A group occurred at 24 weeks. The changes in the
      subdomains of the KHQ were assessed over the study period. RESULTS Overall QoL
      was significantly improved in the BTX-A treated patients compared with placebo in
      the blinded part of the study. When analysing the KHQ subdomains, 'Incontinence
      Impact', 'Emotions', 'Physical Limitations', 'Social Limitations' and 'Severity
      Measures' were significantly improved in those that received BTX-A compared with
      placebo. The 'Symptom Severity' domain was also significantly improved at 4 weeks
      but not at 12 weeks. At 12 weeks 'Role Limitations' also became statistically
      significant in favour of BTX-A. The open-label extension study suggested these
      benefits last for at least 24 weeks. CONCLUSIONS BTX-A bladder injections at 200
      U appear to improve QoL in patients with OAB symptoms and IDO refractory to
      anticholinergics for at least 24 weeks. As well as the improvement seen in
      clinical parameters with this form of therapy, perhaps of more importance to the
      patient, is the improvement in QoL.

PMID- 19389020
TI  - Liquid storage of marrow stromal cells.
AB  - BACKGROUND: Marrow stromal cells (MSCs) for clinical trials are inevitably stored
      before administration, but little is known about the effects of storage on MSCs.
      The effects of short-term liquid storage on the in vitro function of MSCs
      intended for a clinical trial were studied. STUDY DESIGN AND METHODS: Early
      passage human MSCs were suspended in 0.9% saline or culture medium and stored at
      4 degrees C or room temperature for up to 72 hours followed by assessment of cell
      loss, viability, and growth in culture. RESULTS: When stored in saline at 4
      degrees C, MSC counts decreased by 5% to 20%, MSC viability decreased 17% to 37%,
      and MSC growth decreased 65% to 100% after 24-hour storage. Similar results were
      obtained by MSC storage at room temperature or in Dulbecco's modified Eagle's
      medium or by addition of 1% human serum albumin (HSA) from two manufacturers.
      Storage of MSCs in saline with HSA from a third manufacturer maintained MSC
      viability at prestorage levels and improved poststorage MSC growth versus saline
      (32 +/- 9% vs. 9 +/- 9%; p < 0.05) or saline with two other HSA preparations (4
      +/- 4 and 8 +/- 11%; p < 0.05). CONCLUSION: MSCs stored at 4 degrees C or room
      temperature, in saline or culture medium, rapidly become nonviable. HSA
      preparations vary significantly in their ability to maintain poststorage MSC
      viability and growth. These results provide insight regarding the effects of
      storage on MSCs and indicate the need to screen HSA preparations before their use
      as additives to preserve MSCs during short-term liquid storage.

PMID- 19389021
TI  - A prospective, double-blind, randomized clinical feasibility trial of controlling
      the storage age of red blood cells for transfusion in cardiac surgical patients.
AB  - BACKGROUND: Recent evidence demonstrates an association between duration of
      storage of red blood cells (RBC) and morbidity and mortality after cardiac
      surgery. We studied the feasibility of two different schemes for categorizing and
      randomizing age of RBC units transfused in cardiac surgical patients. STUDY
      DESIGN AND METHODS: In Phase 1, 20 subjects were randomly assigned to standard of
      care (SOC) versus no RBCs with more than 21 days' storage duration. In Phase 2,
      23 subjects were randomized to RBCs of 7 +/- 4 versus 21 +/- 4 days' storage
      duration. The age of study RBC units was masked. RESULTS: In Phase 1, no patients
      received RBCs 31 days or older in SOC, and there was overlap in storage age
      shared in both arms so the predefined feasibility criteria were not met. In Phase
      2, it was feasible to deliver specified age RBCs to the 7-day arm (achieved in
      100% of subjects), but feasibility was not demonstrated for the 21-day arm (only
      50% of subjects transfused with target age RBCs). Significant differences,
      however, were observed between the 7 +/- 4- and 21 +/- 4-day arms with respect to
      age of all RBC units (6 +/- 2 vs. 18 +/- 7, p = 0.0002) and maximum age (7 +/- 2
      vs. 20 +/- 7, p < 0.0001). CONCLUSION: Given the current storage age distribution
      of available RBC inventory, use of a SOC arm in future studies is unlikely to
      result in a large exposure to "old" blood. It is feasible to randomize patients
      to "younger" RBCs (3-11 days) but design strategies are needed to provide
      "intermediate-aged" or "old" blood as a comparator.

PMID- 19389022
TI  - Universal adoption of pathogen inactivation of platelet components: impact on
      platelet and red blood cell component use.
AB  - BACKGROUND: Pathogen inactivation of platelet (PLT) components (INTERCEPT Blood
      System, Cerus Europe) was implemented into routine practice at a blood center
      supporting a tertiary care hospital. Utilization of platelet components (PCs) and
      red blood cell (RBC) components was analyzed for 3 years before and 3 years after
      introduction of pathogen inactivation to assess the impact of pathogen
      inactivation on component use. STUDY DESIGN AND METHODS: This was a retrospective
      analysis of prospectively collected data. An electronic database used in routine
      blood bank hemovigilance to monitor production and use of blood components was
      analyzed to assess clinical outcomes. RESULTS: Transfusion records were analyzed
      for 688 patients supported with conventional PCs and 795 patients supported with
      pathogen inactivation PCs. Additional analyses were conducted for intensively
      transfused hematology patients. Patient demographics (age category, sex, and
      diagnostic category) were not different in the two observation periods. For all
      patients, mean numbers of PC per patient were not different for conventional PCs
      and pathogen inactivation PCs (9.9 +/- 19.5 vs. 10.1 +/- 20.9, p = 0.88). Data
      for hematology patients (272 conventional PCs and 276 pathogen inactivation PCs)
      confirmed that days of PLT support were not different (31.6 +/- 42.6 vs. 33.1 +/-
      47.9, p = 0.70) nor was total PLT dose (10(11)) per patient (87.3 +/- 115.4 vs.
      88.1 +/- 111.6, p = 0.93). RBC use, for all patients and hematology patients, was
      not different in the two observation periods, either during periods of PLT
      support or outside periods of PLT transfusion support. CONCLUSION: Pathogen
      inactivation of PCs had no adverse impact on component use during a 3-year
      observation period of routine practice.

PMID- 19389023
TI  - Membrane array-based differential profiling of platelets during storage for 52
      miRNAs associated with apoptosis.
AB  - BACKGROUND: Enucleated platelets (PLTs) utilize posttranscriptional gene (mRNA)
      regulation (PTGR) for their normal morphologic and physiologic functions, which
      are altered in their ex vivo storage, also collectively referred to as storage
      lesions. While cellular micro-RNAs (miRNAs) play a significant role in
      posttranscriptional gene (mRNA) regulation by binding to their target mRNAs,
      comprehensive analysis of apoptosis-associated miRNAs and global changes in their
      profiles during PLT storage have not been evaluated to date. STUDY DESIGN AND
      METHODS: In this report room temperature-stored PLTs of Days 0, 2, and 9 were
      analyzed by differential profiling for 52 apoptosis-associated human miRNAs.
      After total RNA extraction from the samples, a membrane array-based miRNA
      analysis was carried out. Prediction of target genes was performed by
      bioinformatics-based approaches. RESULTS: Our analysis revealed that during
      storage, Let-7a, -7c, -7e, -7f, -7g, and -7i miRNA profiles of the PLTs were
      barely detectable, while levels of miR-150, -151, -152, -184, -188, -196a, -197,
      and -202 remained at high levels in PLTs. The rest of the miRNA levels were in
      between. However, two miRNAs, Let-7b and miR-16, distinctly demonstrated an
      increasing trend while miR-7 and miR-145 showed a decreasing profile during PLT
      storage. For these four miRNAs, we also identified their potential target mRNAs.
      CONCLUSIONS: Overall, these results confirm the fact that miRNAs do exist in
      PLTs, and among 52 apoptosis-specific miRNAs studied, only a few selected miRNAs
      did perturb during PLT storage. Future experimental evaluation of these miRNA
      target mRNA interactions will provide new insights into the molecular mechanisms
      of PLT storage-associated lesions.

PMID- 19389024
TI  - Discovery and analysis of a novel parvovirus B19 Genotype 3 isolate in the United
      States.
AB  - BACKGROUND: Parvovirus B19 (B19V) is a pathogen frequently identified in human
      plasma donations through the detection of nucleic acids. Three B19V genotypes
      have been defined based on isolates having greater than 10% divergence in overall
      DNA sequence. B19V Genotype 3 is a rarely occurring genotype that has been
      detected primarily in Ghana with sporadic reports in Brazil and France but has
      not been previously reported in North America. STUDY DESIGN AND METHODS: A
      polymerase chain reaction assay was developed with broad specificity for B19V
      detection. The performance of this assay was assessed by testing approximately
      440,000 clinical samples representing more than 81,000 individual donors.
      Determinations of B19V titer, DNA sequence, and antibody concentrations were
      performed on samples of interest. RESULTS: This assessment identified a series of
      eight plasma donations spanning 28 days from a single donor in the United States
      infected with B19V Genotype 3 as confirmed by DNA sequence analysis. The B19V
      titer of this series of donations showed virus titers that peaked at greater than
      10(11) IU/mL. The virus titer decreased significantly over the next several
      donations coinciding with an increase in immunoglobulin M (IgM) levels. The
      immunoglobulin G levels also increased but lagged approximately 7 days behind the
      IgM levels. CONCLUSION: This is the first report of a B19V Genotype 3 detected
      from a plasma donor located in the United States. Although our data are
      consistent with recent reports suggesting low incidence for this genotype, they
      indicate its increasing relevance among blood and plasma donors.

PMID- 19389025
TI  - The risk of dengue transmission by blood during a 2004 outbreak in Cairns,
      Australia.
AB  - BACKGROUND: Dengue virus (DENV) is a Flavivirus transmitted by the Aedes
      mosquito. The related arbovirus, West Nile virus, has been shown to be
      transfusion transmitted, which, added to the four recorded dengue transfusion
      associated cases, indicates that DENV is also transfusion transmitted. The
      purpose of this study was to assess the risk of transfusion-transmitted DENV
      during a 2004 outbreak in the Australian city of Cairns. STUDY DESIGN AND
      METHODS: A mathematical model was constructed to estimate the risk of transfusion
      transmitted dengue. The model's central premise is that the transmission risk is
      proportional to the frequency of dengue-viremic donations and correlates with the
      incidence of asymptomatic dengue viremia among the population at large. RESULTS:
      The modeling predicted that the total number of DENV infections (clinical plus
      subclinical) among the population at large during the entire outbreak ranged from
      156 to 569 with the epidemic peak occurring between February 8 and March 6, 2004.
      The overall transmission risk during the entire outbreak was estimated as 1 in
      19,759 (range, 1 in 3404 to 75,486) peaking at 1 in 5968 (range 1 in 1028 to
      22,800). CONCLUSION: By use of the most conservative estimates for key variables,
      the risk of collecting a viremic donation could have been as high as 1 in 1028
      during the peak of the 2004 outbreak. The model can be used to determine
      transfusion transmission risk levels during DENV outbreaks and inform decisions
      as to when fresh component restriction measures are required to minimize
      transfusion transmission risk.

PMID- 19389026
TI  - Implementation of a two-specimen requirement for verification of ABO/Rh for blood
      transfusion.
AB  - BACKGROUND: This study presents our implementation of a two-specimen requirement
      with no prior record of ABO/Rh to verify patients' blood type before transfusion.
      MATERIALS AND METHODS: Blood type verification was introduced, discussed,
      approved, and implemented over a 12-month period (May 2007 to May 2008).
      Potential barriers and impact on benchmark indicators were identified and
      tracked. RESULTS: Inpatient identification and/or specimen labeling for nursing
      and laboratory phlebotomists baseline corrected error rates were 1:467 and
      1:5555, respectively. This study therefore sought and obtained approval to
      initiate a new policy of blood type verification before blood transfusion.
      Compliance in turnaround time (TAT) before and after implementation for
      completion of STAT type and screen/crossmatch within 60 minutes worsened
      marginally, from 90% to 80%. The impact on use of O-, uncrossmatched blood was
      found to be manageable. Seven (of 25 total) recorded electronic complaints were
      received after implementation. The corrected error rate for nurse phlebotomy
      draws after implementation was 1:630. CONCLUSION: Despite the lack of an
      instigating event, verification of blood type before blood transfusion was
      successfully implemented. An impact on resources and benchmark indicators such as
      TAT can be anticipated and managed. Further process improvement efforts will be
      needed to ensure safety (e.g., at time of blood transfusion) for patients
      receiving blood transfusions. ABO/Rh verification may be necessary even after
      future implementation of bar coding and/or RFID chips, because human errors
      continue to occur even with systems improvements.

PMID- 19389027
TI  - Age- and gender-specific distributions of hepatitis B virus (HBV) genotypes in
      Japanese HBV-positive blood donors.
AB  - BACKGROUND: There are an increasing number of reports on the hepatitis B virus
      (HBV) genotype distribution in acute or chronic HBV-infected patients in Japan;
      however, reports on the HBV genotype of blood donors are few. To compare the HBV
      genotypes of hepatitis B surface antigen (HBsAg)-positive blood donors with
      infected patients, all the HBsAg-positive donors' genotypes were determined.
      STUDY DESIGN AND METHODS: Data on Japanese blood donors from October 2006 to
      September 2007 were obtained from the Japanese Red Cross database. The number of
      available samples was 1979, and the HBV genotypes were determined in 1887
      samples. The six major genotypes of HBV (A-F) were determined by enzyme-linked
      immunosorbent assay. The presence of the immunoglobulin M (IgM) antibody against
      the HBV core antigen was determined by enzyme immunoassay among all HBsAg
      positive donors. RESULTS: A significant difference in the HBV genotype
      distribution between donors and patients was in the C/B genotype ratio. The
      ratios were low in blood donors (2.0-3.9) and high in patients (5.3-18.2). The
      genotype B ratio increases from 13.8% in teenage donors to 42.4% in those in
      their 50s; however; the genotype C ratio decreases from 83.1% in teenage donors
      to 55.1% in those in their 50s. In both IgM antibody against hepatitis B core
      antigen and nucleic acid test-positive donors, genotypes A and B were restricted
      to male donors. CONCLUSIONS: The age-specific distribution of HBV genotypes in
      Japanese blood donors was observed in the B/C genotype ratio. The gender-specific
      distribution of HBV genotype A, which originated from the US or Western
      countries, was observed in male Japanese donors.

PMID- 19389028
TI  - Pilot trials in transfusion medicine.

PMID- 19389029
TI  - Analysis of transfusion reactions associated with prestorage-pooled platelet
      components.
AB  - BACKGROUND: The goal of this study was to assess transfusion reactions arising
      from prestorage-pooled platelet (PSPP) infusions compared with apheresis single
      donor platelets (SDPs) and poststorage-pooled, whole blood-derived random-donor
      platelets (RDPs). STUDY DESIGN AND METHODS: Over a span of 18 months, transfusion
      reaction records of patients receiving platelet (PLT) infusions were
      retrospectively reviewed at two academic, tertiary care hospitals. Chi-square
      analysis was used for statistical comparisons; significance was a p value of less
      than 0.05. RESULTS: For the two sites, 10,251 prestorage-leukoreduced PLT
      products were infused including 4731 PSPPs, 3999 SDPs, and 1521 RDPs. Of the
      total infusions, 0.91% (93/10,251) were associated with a transfusion reaction.
      The aggregate transfusion reaction rate was 0.89% (42/4731) for PSPPs, 0.75%
      (30/3999) for SDPs, and 1.38% (21/1521) for RDPs. There were no significant
      differences in total reaction rate between PSPPs and the other PLT products (p >
      0.05). Allergic transfusion reactions were the most common adverse event for PLT
      products evaluated (63/10,251; 0.61%) and febrile reactions were second most
      common (27/10,251; 0.26%). There were 2 suspected cases of sepsis (1 associated
      with PSPP and 1 associated with RDP; both culture negative) and 1 case of volume
      overload associated with RDP infusion. There were no significant differences in
      aggregate allergic or febrile reaction rates among the 93 PLT products evaluated
      (p > 0.05). No reports of transfusion-related acute lung injury or hemolysis were
      noted. CONCLUSIONS: No difference in reactions rates was observed among PSPPs and
      the other PLT products. The transfusion reactions occurring in this population
      were not dependent on the type of PLT product infused.

PMID- 19389030
TI  - Evaluation of immunohematologic routine methods using the new erythrocyte
      magnetized technology on the QWALYS 2 system.
AB  - BACKGROUND: QWALYS 2 is a fully automated system for ABO/D grouping, Rh
      phenotyping, K typing, and antibody screening (ABS). Its new erythrocyte
      magnetized technology (EMT) is based on the use of magnetic nanoparticles and
      avoids centrifugation and washing steps. STUDY DESIGN AND METHODS: Overall 499
      blood samples were tested with our routine blood bank methods for ABO/D grouping,
      313 samples for Rh phenotyping and K typing (microtiter plates; Olympus PK 7200),
      and 478 samples for ABS (gel centrifugation technique, DiaMed). All samples were
      tested in parallel with the EMT. RESULTS: In 496 of 499 samples (99.4%), a
      complete concordance between the observed (QWALYS 2) and the expected results for
      ABO/D grouping was found. One sample with a weak A in an AB blood group and 2
      samples with a weak D were not detected by the QWALYS system. Rh phenotyping and
      K tests revealed a 100% concordance. In the two ABS techniques, 427 samples were
      negative in both and 15 samples showed the same antibody specificity in both.
      Three immunoglobulin M antibodies were as expected negative in EMT and positive
      by DiaMed. In 32 cases (6.7%), false-positive reactions were observed by EMT due
      to 22 unspecific reactions (4.6%) and 10 lipemic or fibrinic plasmas (2.1%). One
      autoantibody was found by EMT only. CONCLUSION: The EMT is reliably suited to
      ABO/D grouping, Rh phenotyping, and K testing and is suitable to detect
      immunoglobulin G red blood cell alloantibodies as well. The rate of false
      positive reactions in ABS due to lipemic and fibrinic samples needs to be
      reduced.

PMID- 19389031
TI  - Aorta and coronary angiographic follow-up of children with severe
      hypercholesterolemia treated with low-density lipoprotein apheresis.
AB  - BACKGROUND: In this single-center, nonrandomized, prospective study, 11 children
      with severe genetic hypercholesterolemia, without previous cardiovascular disease
      events, were treated with low-density lipoprotein apheresis (LDLa). STUDY DESIGN
      AND METHODS: LDLa was given every 1 or 2 weeks for 2 to 17 years. Clinical
      cardiovascular events and coronary revascularization, as well as aortic and
      coronary angiographic findings and ejection fractions, were serially evaluated
      for 2 to 17 years. RESULTS: Total cholesterol (TC) and LDL cholesterol levels at
      baseline were 826.1 +/- 183.3 and 767.8 +/- 181.9 mg/dL, respectively. After
      LDLa, these levels decreased to 122.6 +/- 24.4 and 79.1 +/- 20.7 mg/dL,
      respectively (both differences, p < or = 0.001). There were no cardiac deaths,
      and 6 children were free from any coronary lesions. Nonfatal myocardial
      infarction was not observed, and coronary revascularization was not required in
      any patient. Regression of coronary stenosis in children with existing
      angiographically established lesions after treatment with LDLa was prospectively
      demonstrated. The statistical analysis applicable to a scoring model (overall
      atherogenic index [OAI]) highlighted a significant relation between values of 0
      to 4 years relevant to the score (p < or = 0.018) and a weaker significant
      statistic for the value of OAI between 0 and 2 years (p < or = 0.03). The OAI
      score at baseline was significantly related to the basal values of TC (p =
      0.015), LDL cholesterol (p = 0.015), and triglycerides (p = 0.01), but not of
      high-density lipoprotein cholesterol (p = 0.075) as demonstrated by the logistic
      regression analysis (Cox and Snell pseudo-R(2) of 0.67). CONCLUSION: LDLa
      interrupted the development of new aortic and coronary lesions in the native
      arteries and prevented cardiac events and the need for coronary revascularization
      in children without previous cardiovascular disease events.

PMID- 19389032
TI  - Time course and etiology of death in patients with severe anemia.
AB  - BACKGROUND: Mortality increases as hemoglobin (Hb) levels fall. Among severely
      anemic patients, the clinical course, cause of death, and whether there are any
      warning signs before death are unknown. STUDY DESIGN AND METHODS: A retrospective
      cohort study was performed of surgical patients who refused red blood cell
      transfusions for religious reasons and died with a Hb concentration 6 g/dL or
      less. Mortality was defined as death that occurred during hospitalization.
      RESULTS: Among the 1958 Jehovah's Witness patients that had surgery, 117 (5.6%)
      had a postoperative Hb level of 6 g/dL or less and 39 (33.3%) of these
      individuals died in the hospital. The median number of days from surgery to the
      lowest Hb level was 3 days (range, 0-22 days; interquartile range, 1-8 days) and
      from the lowest postoperative Hb level to death was 2 days (range, 0-40 days;
      interquartile range, 1-12 days). Individuals with a Hb level of 2.0 g/dL or less
      had on median 1.0 (interquartile range, 0.5-1.5) day from their lowest Hb to
      death while individuals with their lowest Hb ranging between 4.1 and 5.0 g/dL had
      on median 11 (interquartile range, 1-23) days from their lowest Hb to death.
      Except for anemia, no single etiology of death was predominant. CONCLUSIONS:
      While there does not appear to be any single etiology that can be predictive or
      preventative of mortality for anemic patients, individuals with very low Hb
      concentrations often do not die quickly. Thus, there appears to be a potential
      time window where transfusion medicine physicians may intervene.

PMID- 19389033
TI  - Changes in Band 3 oligomeric state precede cell membrane phospholipid loss during
      blood bank storage of red blood cells.
AB  - BACKGROUND: Lipid loss in the form of vesicles contributes to the red blood cell
      (RBC) storage lesion, and this loss of lipid is correlated with changes in
      membrane protein function. Sensitive spectroscopic techniques were used to
      measure changes in Band 3 oligomeric state during storage of RBCs, compared to
      metabolic changes and phospholipid loss. The aim of the study was to determine
      whether changes in the macromolecular organization of membrane proteins occur
      before, coincident with, or after lipid loss during RBC storage. STUDY DESIGN AND
      METHODS: Five RBC units were collected from normal volunteers and stored under
      standard blood bank conditions, and both metabolic changes and lipid loss were
      measured by multiple assays. Band 3 oligomeric state was assessed by time
      resolved phosphorescence anisotropy and fluorescence resonance energy transfer of
      eosin-5-maleimide-labeled RBC ghosts. RESULTS: Extracellular pH decreased and
      extracellular potassium increased rapidly during cold storage of blood. Band 3 on
      the RBC membrane exhibited a shift from small to large oligomers early in the
      storage period and before detectable loss of phospholipid from the RBC membrane.
      The immobilized fraction of Band 3, that which is tethered to the cytoskeletal
      network via spectrin and ankyrin, did not change during cold storage. CONCLUSION:
      Our results demonstrate that changes in the macromolecular organization of
      membrane proteins on the RBC occur early in storage, and these changes may induce
      phospholipid loss, irreversible morphologic changes, and loss of function during
      RBC storage.

PMID- 19389034
TI  - Comparison between the BACTEC 9240 and the Pall eBDS system for detection of
      bacterial platelet concentrate contamination.
AB  - BACKGROUND: Only two commercially available automated systems have been cleared
      by the FDA for screening of bacterial contamination in platelet (PLT) products.
      These are the Pall eBDS (Pall Corp.), based on measurement of oxygen consumption
      by contaminant organisms, and the BacT/ALERT (bioMerieux), revealing increasing
      carbon dioxide concentration due to bacterial growth. STUDY DESIGN AND METHODS:
      The authors compared the performance of the Pall eBDS with the BACTEC 9240
      (bioMerieux) in detecting PLT contamination. Serial dilutions of 10 bacterial
      species frequently associated with PLT contamination were prepared in an
      apheresis PLT unit per organism. Units were from single donors. After 30 minutes
      from seeding PLT units, a volume of suspension achieving a final bacterial
      concentration of 1 to 10 colony-forming units/mL for each unit was inoculated in
      two Pall bags and a BACTEC bottle, and the same was done after 24 hours from
      seeding. Measurements were performed at 24 and 30 hours. RESULTS: Significant
      differences between the two instruments were only found when screening PLT units
      after 24 hours from seeding. The Pall system showed a higher sensitivity than
      BACTEC 9240, because it revealed 97 and 98% of positive samples at 24 and 30
      hours of incubation, respectively, whereas the second detected 86 and 90% of
      contaminated products. Significance was lost after 35-hour incubation with the
      BACTEC 9240. CONCLUSIONS: By comparing the two instruments, their performances
      were found to be comparable; the Pall system appeared as a more suitable method
      when using 24 to 30 hours as times for readings, but the significant difference
      was lost after 35-hour incubation.

PMID- 19389035
TI  - How do we provide blood products to trauma patients?

PMID- 19389036
TI  - Characteristics of blood donors and donated blood in sub-Saharan Francophone
      Africa.
AB  - BACKGROUND: The importance of blood safety in public health was recognized long
      ago, and data are essential to plan strategies to improve the status. This study
      aims to obtain data on blood donor and blood donation characteristics that would
      complement blood safety data from national and international organizations.
      MATERIALS AND METHODS: A questionnaire was sent to seven Francophone countries
      (Burkina Faso, Cameroon, Congo, Ivory Coast, Mali, Niger, and Rwanda) and was
      structured to obtain objective data on blood donors and donated blood and in
      administrative and technical organization. RESULTS: The results reflect a poor
      level of organization of blood transfusion centers in large regions of the
      African continent, insufficient supply of blood products, high prevalence of
      transfusion-transmitted infections, limited financial resources, a lack of well
      trained personnel, and cultural obstacles. Six countries had less than 50% of
      their personnel trained in transfusion medicine. Only one country had the entire
      standard operating procedure written. Female donors represented less than 30% of
      the donors and the range of percentage of hepatitis B found in donors was 2.76%
      to 18.96%. CONCLUSION: The inclusion of these regions in future blood safety
      surveys and in the development of national blood transfusion programs is
      essential and will undoubtedly require the assistance of international
      organizations.

PMID- 19389037
TI  - Community health insurance in sub-Saharan Africa: what operational difficulties
      hamper its successful development?
AB  - In recent years, a number of reviews have generated evidence on the potential of
      community health insurance (CHI) to increase access to care and offer financial
      protection against the cost of illness for poor people excluded from formal
      insurance systems. Field experience, however, shows that in sub-Saharan Africa
      (SSA), a series of operational difficulties still hampers the successful
      development of CHI, yielding negative effects on potential progress towards
      increased access to care and improved financial protection. Through a careful
      assessment of the existing literature, including peer-reviewed articles, books,
      consultancy reports, and manuscripts from international organizations, we produce
      an analytical review of such difficulties. Our aim is to provide policy makers
      with the necessary knowledge on the problems at stake and with policy
      propositions to offset such problems, strengthening CHI and enhancing its role
      within SSA health systems. Our review of the literature reveals that the major
      difficulties currently faced by CHI in SSA are operational in nature and cluster
      around five areas: (i) lack of clear legislative and regulatory framework; (ii)
      low enrolment rates; (iii) insufficient risk management measures; (iv) weak
      managerial capacity; and (v) high overhead costs. Consequently, our review calls
      for appropriate policy interventions, specifically: (i) greater commitment
      towards the development of adequate legislation in support of CHI; (ii)
      increasing uptake of measures to expand equitable enrolment; (iii) the adoption
      of adequate risk management measures in all schemes; (iv) substantial investments
      from host countries as well as from sponsoring agencies to improve managerial
      capacity; and (v) collective efforts to contain overhead costs.

PMID- 19389038
TI  - Cattle, other domestic animal ownership, and distance between dwelling structures
      are associated with reduced risk of recurrent Plasmodium falciparum infection in
      southern Zambia.
AB  - OBJECTIVES: To examine the associations between household Plasmodium falciparum
      infection and a number of factors including domestic animal ownership, potential
      mosquito breeding sites, indoor darkness, density of people, distance between
      dwelling structures, and insecticide-treated bed net use. METHODS: Analyses were
      based on data collected from a household survey conducted in Macha, Zambia.
      Thirty-four households with recurrent malaria infection in 2005-2008 were
      selected as case households and compared with 37 control households with no
      malaria infection randomly selected from the same geographic area. Logistic
      regression models were used to identify factors associated with household P.
      falciparum infection. RESULTS: In multivariate analysis, cattle ownership was
      associated with reduced risk of P. falciparum infection (adjusted odds ratio =
      0.19; 95% CI = 0.05-0.69), as was increased distance between dwelling structures
      (aOR = 0.26; 95% CI = 0.07-0.98). Ownership of the highest category of cattle,
      goats, dogs, or cats dramatically reduced the risk of P. falciparum infection
      (aOR = 0.13; 95% CI = 0.03-0.56). CONCLUSION: Domestic animal, in particular
      cattle, ownership and greater distance between dwelling structures were
      associated with reduced risk of recurrent P. falciparum infection at the
      household level. These factors should be further investigated as supplemental
      measures for malaria control in rural African settings.

PMID- 19389039
TI  - Recasting the role of the surgeon in Uganda: a proposal to maximize the impact of
      surgery on public health.
AB  - A growing body of recent evidence supports the essential role of surgical
      services in improving population health in low-income countries. Nonetheless,
      access to surgical services in Uganda, as in many low income countries, is
      severely limited, largely due to constraints in human resources, infrastructure
      and supplies. To maximize the impact of surgical services on population health in
      the context of Uganda's limited surgical workforce, we propose a 'recasting' of
      the role of the surgeon. Traditionally, the surgeon has played primarily a
      clinical role in patient care. The demands and isolation of this role have
      limited the ability of the surgeon to tackle health systems issues related to
      surgery. Now, the clinical and educational role played by surgeons must be
      redefined, and the surgeon must also assume a greater role in leadership,
      management and public health advocacy by documenting the unmet need for surgery
      and the resources required to improve access to care. Policy and incentives for
      specialist surgeons to spend amounts of time apportioned to these roles should be
      developed and supported by health care institutions. Political leadership and
      commitment will be critical to realizing this ideal. Such a model may be
      applicable to other countries seeking to maximize the impact of surgical services
      on population health.

PMID- 19389040
TI  - Applying concepts of generalizability theory on data from experimental pain
      studies to investigate reliability.
AB  - This work demonstrates how full modelling power in statistically mixed models can
      be used to study generalizability (reliability) coefficients of advanced data
      from human experimental pain studies utilizing placebo data from drug screening
      trials. This can be used to help optimizing outcome parameters from existing data
      sets.

PMID- 19389041
TI  - Diesel exhaust particles: effects on neurofunction in female mice.

PMID- 19389042
TI  - Oxidative stress alters creatine kinase system in serum and brain regions of
      polychlorinated biphenyl (Aroclor 1254)-exposed rats: protective role of
      melatonin.
AB  - Polychlorinated biphenyls are one of the environmental toxicants and neurotoxic
      compounds which induce the production of free radicals. Creatine kinase plays a
      key role in energy metabolism of nervous tissue and might be one of the targets
      for reactive oxygen species. Melatonin, an indoleamine, plays an important role
      in neurodegenerative diseases as an antioxidant and neuroprotector. The objective
      of the present study was to investigate the protective role of melatonin on
      polychlorinated biphenyl (Aroclor 1254)-induced oxidative stress and the changes
      in creatine kinase activity in brain regions of adult rats. Group I: rats were
      intraperitoneally (i.p.) administered with corn oil (vehicle) for 30 days. Group
      II: rats injected i.p. with Aroclor 1254 at 2 mg/kg body weight (bw)/day for 30
      days. Groups III and IV: rats i.p. received melatonin (5 or 10 mg/kg bw/day)
      simultaneously with Aroclor 1254 for 30 days. After 30 days, rats were killed and
      the brain regions were dissected to cerebral cortex, cerebellum and hippocampus.
      Lipid peroxidation, hydroxyl radical and hydrogen peroxide (H2O2) levels were
      determined. The activity of creatine kinase was assayed in serum and brain
      regions, and its isoenzymes in serum were separated electrophoretically. Activity
      of creatine kinase was decreased while an increase in H2O2, hydroxyl radical and
      lipid peroxidation was observed in brain regions of polychlorinated biphenyl
      treated rats. Also polychlorinated biphenyl exposure showed a significant
      increase in serum creatine kinase level and its isoforms such as BB-creatine
      kinase, MB-creatine kinase, and MM-creatine kinase. Administration of melatonin
      prevented these alterations induced by polychlorinated biphenyl by its free
      radical scavenging mechanism. Thus, polychlorinated biphenyl alters creatine
      kinase activity by inducing oxidative stress in brain regions, which can be
      protected by melatonin.

PMID- 19389043
TI  - Effect of N-acetyl cysteine against aluminium-induced cognitive dysfunction and
      oxidative damage in rats.
AB  - Aluminium is a potent neurotoxin involved in the initiation and progression of
      various cognitive disorders like Alzheimer's disease. Chronic aluminium exposure
      induces oxidative stress and increases amyloid beta levels in vivo. The role of
      oxidative stress has been well-suggested in these cognitive problems. Therefore,
      the present study was designed to explore the possible role of N-acetyl cysteine
      against aluminium mediating cognitive dysfunction and oxidative stress in rats.
      Aluminium chloride (100 mg/kg, p.o.) was given to rats daily for 6 weeks. N
      acetyl cysteine (per se; 50 and 100 mg/kg, i.p.) pre-treatment was given 30 min.
      before aluminium daily for 6 weeks. On the third (21st day) and sixth week (42nd
      day) of the study, various behavioural tests (Morris water maze and elevated plus
      maze task paradigms) and locomotion (photoactometer) were done to evaluate
      cognitive tasks. The rats were killed on the 43rd day following the last
      behavioural test, and various biochemical tests were performed to assess the
      extent of oxidative damage. Chronic aluminium chloride administration resulted in
      poor retention of memory in Morris water maze, elevated plus maze task paradigms
      and caused marked oxidative damage. It also caused a significant increase in the
      acetylcholinesterase activity. Chronic administration of N-acetyl cysteine
      significantly improved memory retention in tasks, attenuated oxidative damage and
      acetylcholinesterase activity in aluminium-treated rats. The study suggests a
      neuroprotective effect of N-acetyl cysteine against aluminium-induced cognitive
      dysfunction and oxidative damage.

PMID- 19389044
TI  - Toxicological investigation and antinociceptive property of potassium thiophene-3
      trifluoroborate.
AB  - The aim of the present study was to evaluate pharmacological and toxicological
      properties of potassium thiophene-3-trifluoroborate (RBF(3)K). The acute effect
      of RBF(3)K was evaluated on mice. To this end, mice received a single dose of
      RBF(3)K (25, 50, and 100 mg/kg, by oral route, p.o.) and after 72 hrs, blood,
      liver, and kidney samples were collected. delta-Aminolevulinate dehydratase,
      catalase and glutathione-S-transferase activities, thiobarbituric acid-reactive
      substances and vitamin C levels, as well as plasma aspartate and alanine
      aminotransferase activities and creatinine levels were determined. Hepatic and
      renal lipid peroxidation levels in treated mice did not differ from those in
      control mice. No significant differences between treated and control mice were
      detected in hepatic and renal delta-aminolevulinate dehydratase activity.
      Aspartate and alanine aminotransferase activities as well as urea and creatinine
      levels were similar among the groups. In contrast, results obtained from in vivo
      experiments revealed that RBF(3)K, orally administered, reduced peritoneovisceral
      pain induced by acetic acid administered i.p. Doses of 1, 5, 10, 25, 50, and 100
      mg/kg of RBF(3)K were assessed in the antinociceptive investigation and the
      effect was significantly different than control groups from 5 mg/kg. It was
      observed that alpha(2-)adrenergic and serotonergic, but not opioidergic,
      receptors appear to be involved in orally administered RBF(3)K. Mice treated with
      RBF(3)K did not reveal any motor impairment in the open field. This is a
      promising compound for more detailed pharmacological studies involving
      organotrifluoroborate compounds.

PMID- 19389045
TI  - Azithromycin treatment modulates cytokine production in Chlamydia trachomatis
      infected women.

PMID- 19389046
TI  - Effects of intrathecal injection of nicotine on the analgesic effects of
      isoflurane in a model of inflammatory pain.
AB  - The present study was designed to investigate the role of spinal neuronal
      nicotinic acetylcholine receptors in the analgesic effects of isoflurane. After
      having established the mice model of analgesia by intraperitoneally injecting
      (i.p.) appropriate doses of isoflurane, nicotine, a neuronal nicotinic
      acetylcholine receptor agonist was intrathecally injected. The effects of
      isoflurane and nicotine on paw licking times and formalin-induced c-fos
      expression in the spinal cord dorsal horn were examined. Our correlative studies
      have shown that isoflurane can decrease the paw licking times and simultaneously
      suppress c-fos expression after injection of formalin in the mice. Nicotine can
      partially antagonize the effects induced by isoflurane above. Spinal neuronal
      nicotinic acetylcholine receptors may be important targets for the analgesic
      effects of isoflurane in formalin pain.

PMID- 19389047
TI  - Investigations of free anthraquinones from rhubarb against alpha
      naphthylisothiocyanate-induced cholestatic liver injury in rats.
AB  - The protective effects of anthraquinones from Rhubarb, a Chinese herbal medicine,
      consisting of the root and rhizome of Rheum palmatum L., R. tanguticum Maxim. Ex
      Balf., or R. officinale Baill. (family Polygonaceae) were investigated and
      compared in rats with liver injury induced by alpha-naphthylisothiocyanate. alpha
      Naphthylisothiocyanate was given intragastrically in rats, liver injury with
      cholestasis developed within 36 hrs, as indicated by characteristic serum levels
      of glutamate-pyruvate transaminase, glutamic oxaloacetic transaminase, total
      bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase and
      total bile acid. The intragastrical administration of rhein, aloe-emodin and
      physione to alpha-naphthylisothiocyanate-treated rats reduced significantly the
      serum level of both glutamate-pyruvate transaminase, glutamic oxaloacetic
      transaminase and the serum total bilirubin, direct bilirubin, alkaline
      phosphatase, gamma-glutamyltransferase and total bile acid. For all hepatic
      biochemical markers and cholestasis index, rhein was most efficient. By
      comparison, the administration of emodin and chrysophanol did not reduce the
      serum levels of hepatic enzymes glutamate-pyruvate transaminase and glutamic
      oxaloacetic transaminase but decreased the levels of serum total bilirubin,
      direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase, and total bile
      acid, showing their partial protective effects on cholestatic liver injury. The
      liver in alpha-naphthylisothiocyanate-treated rats showed cholangiolitic
      hepatitis characterized by intrahepatic cholestasis, necrosis of hepatocytes and
      biliary epithelial cells and bile obstruction. The concurrent intragastrical
      administration of rhein reduced the severity of all morphological alteration,
      especially the neutrophil infiltration and sinusoid congestion. Rhein, aloe
      emodin, and physione all exhibited protective effects on hepatocytes and
      cholangiocytes against alpha-naphthylisothiocyanate-induced damage, whereas
      emodin and chrystophanol provided partial protection.

PMID- 19389048
TI  - Cytometric analysis of cytotoxicity of polyphenols and related phenolics to rat
      thymocytes: potent cytotoxicity of resveratrol to normal cells.
AB  - The chemopreventive and chemotherapeutic actions of polyphenols and related
      phenolics have received considerable attention since these compounds induce
      apoptosis in several types of cancer cells in vitro. A plausible criterion for
      the use of such compounds is that they should not exert any toxic effect on
      normal cells. However, information about the toxicity of polyphenols and related
      phenolics to normal cells is limited. In this study, the effects of polyphenols
      and related phenolics on rat thymocytes were examined by flow cytometric analysis
      with appropriate fluorescent probes. The compounds examined in this study were
      caffeic acid, rosmarinic acid, chlorogenic acid, (+)-catechin, 6-gingerol,
      sesamol, resveratrol, and eugenol. Of these, resveratrol was the most cytotoxic
      on rat thymocytes incubated for 24 hrs with 100 microM of this compound.
      Resveratrol at a concentration of 10 microM or more (up to 100 microM) led to a
      significant dose-dependent increase in the population of dead cells, shrunken
      living cells, annexin V-positive cells and cells with hypodiploidal DNA. In the
      presence of benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD-FMK), a
      pan-inhibitor of caspases, the resveratrol-induced increase in the population of
      cells with hypodiploidal DNA was partially inhibited. Overall, it is suggested
      that resveratrol at a concentration of 10 microM or more induces apoptosis in
      normal cells as well as cancer cells (previously reported elsewhere). Thus, at
      concentrations that are suitable for chemopreventive and chemotherapeutic
      actions, resveratrol may exert a cytotoxic effect on normal cells.

PMID- 19389049
TI  - Physiological effects of a novel immune stimulator drug, (1,4)-alpha-D-glucan, in
      rats.
AB  - The (1,4)-alpha-D-glucan (alpha-D-glucan), derived from medicinal plant,
      Tinospora cordifolia, activates human lymphocytes with downstream synthesis of
      the pro- and anti-inflammatory cytokines, in vitro. We investigated physiological
      and immunological effects of a low and a high dose of alpha-D-glucan (0.5 and 10
      mg/kg), in vivo, testing the hypothesis that intravenous administration of alpha
      D-glucan does not affect haemodynamic, respiratory, haematological, and immune
      responses in normal rats. Male rats (300-400 g) were anaesthetized,
      tracheostomized, and catheterized in one femoral artery and vein. The mean
      arterial blood pressure and heart rate were continuously recorded. The baselines
      for gas exchange, differential blood cell count, and plasma concentration of TNF
      alpha, IL-1beta, IL-4, IL-6, and IFN-gamma were determined. Rats were then
      randomly assigned to controls (n = 7), a low dose (0.5 mg/kg; n = 10), and a high
      dose (10 mg/kg; n = 7) of alpha-D-glucan for a six 6 hr study period. Gas
      exchange, differential cell count, plasma concentration of TNF-alpha, IL-1beta,
      IL-4, IL-6, and IFN-gamma, and mean arterial blood pressure values remained
      within physiological range. Intravenous administration of 10 mg/kg alpha-D-glucan
      created tachycardia, associated with hyperventilation, and significant reductions
      in the blood haemoglobin and haematocrit concentrations. We suggest that these in
      vivo effects of alpha-D-glucan should be considered for future clinical and/or
      experimental trials.

PMID- 19389050
TI  - Regulation of isoprene emission from poplar leaves throughout a day.
AB  - Isoprene is a biogenic hydrocarbon that significantly affects tropospheric
      chemistry. Numerous plant species, including many trees, emit isoprene. Isoprene
      is synthesized by isoprene synthase (IspS), from dimethylallyl diphosphate
      (DMADP) made by the methylerythritol 4-phosphate (MEP) pathway. It has been
      demonstrated that in developing leaves, isoprene emission is regulated by
      transcriptional control of IspS, while in mature leaves subjected to changing
      growth temperature, regulation of emission is shared between IspS and DMADP
      supply from the MEP pathway. Isoprene emission also varies throughout a day, with
      circadian regulation implicated. This study investigated changes in isoprene
      emission capacity, and expression of IspS and the enzymes of the MEP pathway
      throughout several days, with Populus trichocarpa grown at different temperatures
      to induce different levels of isoprene emission. Isoprene emission capacity
      exhibited ultradian regulation, with a period of about 12 h; peak capacity was
      observed at 0300 and 1500 h daily. Several of the enzymes of the MEP pathway had
      previously been suggested to have regulatory roles in the production of other
      plastidic terpenoids, and transcript accumulation for these enzymes, combined
      with in silico promoter analyses, supported a regulatory role for deoxyxylulose 5
      phosphate synthase (DXS) in particular.

PMID- 19389051
TI  - Picking battles wisely: plant behaviour under competition.
AB  - Plants are limited in their ability to choose their neighbours, but they are able
      to orchestrate a wide spectrum of rational competitive behaviours that increase
      their prospects to prevail under various ecological settings. Through the
      perception of neighbours, plants are able to anticipate probable competitive
      interactions and modify their competitive behaviours to maximize their long-term
      gains. Specifically, plants can minimize competitive encounters by avoiding their
      neighbours; maximize their competitive effects by aggressively confronting their
      neighbours; or tolerate the competitive effects of their neighbours. However, the
      adaptive values of these non-mutually exclusive options are expected to depend
      strongly on the plants' evolutionary background and to change dynamically
      according to their past development, and relative sizes and vigour. Additionally,
      the magnitude of competitive responsiveness is expected to be positively
      correlated with the reliability of the environmental information regarding the
      expected competitive interactions and the expected time left for further plastic
      modifications. Concurrent competition over external and internal resources and
      morphogenetic signals may enable some plants to increase their efficiency and
      external competitive performance by discriminately allocating limited resources
      to their more promising organs at the expense of failing or less successful
      organs.

PMID- 19389052
TI  - A guide to using MapMan to visualize and compare Omics data in plants: a case
      study in the crop species, Maize.
AB  - MapMan is a software tool that supports the visualization of profiling data sets
      in the context of existing knowledge. Scavenger modules generate hierarchical and
      essentially non-redundant gene ontologies ('mapping files'). An ImageAnnotator
      module visualizes the data on a gene-by-gene basis on schematic diagrams ('maps')
      of biological processes. The PageMan module uses the same ontologies to
      statistically evaluate responses at the pathway or processes level. The generic
      structure of MapMan also allows it to be used for transcripts, proteins, enzymes
      and metabolites. MapMan was developed for use with Arabidopsis, but has already
      been extended for use with several other species. These tools are available as
      downloadable and web-based versions. After providing an introduction to the scope
      and use of MapMan, we present a case study where MapMan is used to analyse the
      transcriptional response of the crop plant maize to diurnal changes and an
      extension of the night. We then explain how MapMan can be customized to visually
      and systematically compare responses in maize and Arabidopsis. These analyses
      illustrate how MapMan can be used to analyse and compare global transcriptional
      responses between phylogenetically distant species, and show that analyses at the
      level of functional categories are especially useful in cross-species
      comparisons.

PMID- 19389053
TI  - Leaf stomatal responses to vapour pressure deficit under current and CO(2)
      enriched atmosphere explained by the economics of gas exchange.
AB  - Using the economics of gas exchange, early studies derived an expression of
      stomatal conductance (g) assuming that water cost per unit carbon is constant as
      the daily loss of water in transpiration (f(e)) is minimized for a given gain in
      photosynthesis (f(c)). Other studies reached identical results, yet assumed
      different forms for the underlying functions and defined the daily cost parameter
      as carbon cost per unit water. We demonstrated that the solution can be recovered
      when optimization is formulated at time scales commensurate with the response
      time of g to environmental stimuli. The optimization theory produced three
      emergent gas exchange responses that are consistent with observed behaviour: (1)
      the sensitivity of g to vapour pressure deficit (D) is similar to that obtained
      from a previous synthesis of more than 40 species showing g to scale as 1 - m
      log(D), where m is in [0.5,0.6], (2) the theory is consistent with the onset of
      an apparent 'feed-forward' mechanism in g, and (3) the emergent non-linear
      relationship between the ratio of intercellular to atmospheric [CO(2)]
      (c(i)/c(a)) and D agrees with the results available on this response. We extended
      the theory to diagnosing experimental results on the sensitivity of g to D under
      varying c(a).

PMID- 19389054
TI  - Complementary action of jasmonic acid on salicylic acid in mediating fungal
      elicitor-induced flavonol glycoside accumulation of Ginkgo biloba cells.
AB  - The antagonistic action between jasmonic acid (JA) and salicylic acid (SA) in
      plant defence responses has been well documented. However, their relationship in
      secondary metabolite production is largely unknown. Here, we report that PB90, a
      protein elicitor from Phytophthora boehmeriae, triggers JA generation, SA
      accumulation and flavonol glycoside production of Ginkgo biloba cells. JA
      inhibitors suppress not only PB90-triggered JA generation, but also the elicitor
      induced flavonol glycoside production. However, the elicitor can still enhance
      flavonol glycoside production even though the JA generation is totally inhibited.
      Over-expression of SA hydrolase gene NahG not only abolishes SA accumulation, but
      also suppresses the elicitor-induced flavonol glycoside production when JA
      signalling is inhibited. Interestingly, expression of NahG does not inhibit the
      elicitor-induced flavonol glycoside accumulation in the absence of JA inhibitors.
      Moreover, JA levels are significantly enhanced when SA accumulation is impaired
      in the transgenic cells. Together, the data suggest that both JA and SA are
      involved in PB90-induced flavonol glycoside production. Furthermore, we
      demonstrate that JA signalling might be enhanced to substitute for SA to mediate
      the elicitor-induced flavonol glycoside accumulation when SA signalling is
      impaired, which reveals an unusual complementary relationship between JA and SA
      in mediating plant secondary metabolite production.

PMID- 19389055
TI  - Trends in body mass index and waist circumference among New Zealand adolescents,
      1997/1998-2005.
AB  - The objective of the current study is to examine changes in body mass index (BMI)
      and waist circumference among New Zealand adolescents between 1997/1998 and 2005.
      Data were drawn from two cross-sectional studies of high school students in an
      economically disadvantaged region of Auckland. In total, 608 adolescents from the
      1998 survey and 897 adolescents from the 2005 survey participated. The prevalence
      of obesity increased from 19.4% in 1997/1998 to 30.7% in 2005. The mean BMI among
      adolescents significantly increased from 25.3 in 1997/1998 to 27.2 in 2005, with
      the greatest increases at the high end of the distribution. Increases in BMI did
      not differ by age, gender or ethnicity. The mean waist circumference increased
      from 76.2 cm in 1997/1998 to 89.4 cm in 2005, with increases in waist
      circumference measurements at all points in the distribution. The prevalence of
      obesity is increasing rapidly in this sample of ethnically diverse adolescents.
      Corresponding increases in waist circumference measurements suggest that this
      population of New Zealand adolescents are at increased risk for related chronic
      conditions.

PMID- 19389056
TI  - Prevalence of overweight in Bolivia: data on women and adolescents.
AB  - Secondary analysis of Bolivian Demographic and Health Surveys 1994, 1998 and 2003
      revealed a steady raising trend in levels of overweight and obesity among women
      in childbearing age (20-45 years), reaching 30% and 15% respectively in 2003.
      Adolescents' cross-sectional data suggest that overweight and obesity are mainly
      found in urban areas. Applying the Bolivian body mass index-for-age reference,
      obesity reached 5% in adolescents, while overweight affects 14% of adolescents.
      This overview highlights the importance of including the prevention of weight
      gain among the public health nutrition policies in Bolivia.

PMID- 19389057
TI  - Prevalence of obesity among children aged 6-7 years in South-East Serbia.
AB  - A cross-sectional study of the prevalence of obesity in urban and rural areas of
      South-East Serbia was performed on 541 children (273 boys and 268 girls), aged 6
      7 years. Prevalence of obesity in urban boys and girls was 6.3% and 3.8%
      respectively (P > 0.05). Prevalence of obesity in rural boys and girls was 1.1%
      and 3.3% respectively (P > 0.05). The difference in the prevalence of obesity
      between urban boys and rural boys was statistically significant (P < 0.05), while
      the difference between urban and rural girls was insignificant (P > 0.05). Urban
      boys consumed more sweets and fast food compared with rural boys (P < 0.05).
      Urban children spent more time in watching TV compared with rural children (P <
      0.05).

PMID- 19389058
TI  - Physical environmental correlates of childhood obesity: a systematic review.
AB  - Increasing rates of childhood obesity in the USA and other Western countries are
      a cause for serious public health concern. Neighborhood and community
      environments are thought to play a contributing role in the development of
      obesity among youth, but it is not well understood which types of physical
      environmental characteristics have the most potential to influence obesity
      outcomes. This paper reports the results of a systematic review of quantitative
      research examining built and biophysical environmental variables associated with
      obesity in children and adolescents through physical activity. Literature
      searches in PubMed, PsychInfo and Geobase were conducted. Fifteen quantitative
      studies met the inclusion criteria for this systematic review. The majority of
      studies were cross-sectional and published after 2005. Overall, few consistent
      findings emerged. For children, associations between physical environmental
      variables and obesity differed by gender, age, socioeconomic status, population
      density and whether reports were made by the parent or child. Access to equipment
      and facilities, neighborhood pattern (e.g. rural, exurban, suburban) and urban
      sprawl were associated with obesity outcomes in adolescents. For most
      environmental variables considered, strong empirical evidence is not yet
      available. Conceptual gaps, methodological limitations and future research
      directions are discussed.

PMID- 19389059
TI  - Efficacy of behavioural interventions in managing atypical antipsychotic weight
      gain.
AB  - Atypical antipsychotic treatment is associated with weight gain and increased
      metabolic risk. This systematic literature review evaluates the current research
      on the effectiveness of behavioural interventions in treating and preventing
      atypical antipsychotic weight gain and reducing metabolic risk, describes
      characteristics of interventions implemented and discusses findings in the
      context of the RE-AIM framework. Sixteen studies were identified. When initiated
      at the start of treatment with an atypical antipsychotic agent, behavioural
      weight loss interventions decreased the amount of weight gain associated with
      atypical antipsychotic treatment. When behavioural interventions were initiated
      after the start of atypical antipsychotic treatment, these interventions were
      associated with weight loss. Mean weight losses across studies by treatment
      duration were 2.63 kg for 12- to 16-week interventions, 4.24 kg for 6-month
      interventions and 3.05 kg for 12- to 18-month interventions. Behavioural weight
      loss interventions were also found to improve insulin regulation and HbA1c. In
      addition to assessing efficacy, future studies should evaluate other components
      of the RE-AIM framework, including reach, adoption, implementation and
      maintenance. This information will be useful in determining what types of
      interventions are both effective and practical for delivery in health care or
      community mental health settings.

PMID- 19389061
TI  - Adiponectin: from obesity to cardiovascular disease.
AB  - Adiponectin is an adipokine whose biosynthesis is deranged in obesity and
      diabetes mellitus, predisposing to atherosclerosis. Evidence suggests that
      adiponectin has anti-atherogenic properties by improving endothelial function and
      having anti-inflammatory effects in the vascular wall. In addition, adiponectin
      modifies vascular intracellular redox signalling and exerts indirect antioxidant
      effects on human myocardium. However, its clinical role in cardiovascular disease
      is obscure. Adiponectin's positive prognostic value in coronary artery disease
      had been widely supported over the last years, but this view has been questioned
      recently. High adiponectin levels are paradoxically associated with poorer
      prognosis in heart failure syndrome. These controversial findings seem surprising
      as adiponectin has been viewed overall as an anti-atherogenic molecule.
      Therefore, any certain conclusion about adiponectin's role in cardiovascular
      disease seems premature. Despite the rapidly accumulating literature on this
      adipokine, it is still unclear whether adiponectin is a key mediator or a
      bystander in cardiovascular disease. It is still uncertain whether adiponectin
      levels have any clinical significance for risk stratification in cardiovascular
      disease or they just reflect the activation of complex and opposing underlying
      mechanisms. Circulating adiponectin levels should be interpreted with caution, as
      they may have completely different prognostic value, depending on the underlying
      disease state.

PMID- 19389060
TI  - Attrition from randomized controlled trials of pharmacological weight loss
      agents: a systematic review and analysis.
AB  - Clinical trials of obesity treatments have been limited by substantial dropout.
      Participant-level variables do not reliably predict attrition, and study-level
      variables have not yet been examined. We searched MEDLINE and identified 24 large
      randomized controlled trials of weight loss medications. These trials were
      comprised of 23 placebo and 32 drug groups. Two authors independently extracted
      the following for each treatment group: (i) treatment received; (ii) design
      characteristics (inclusion of a lead-in period, selection of participants with
      weight-related comorbidities, study location and number of study visits); (iii)
      sample characteristics (sample size, % female, and mean baseline age and body
      mass index); and (iv) attrition (total, adverse event [AE]-related and non-AE
      related) at 1 year. The primary outcome was total attrition, which was
      significantly related to treatment (i.e. 34.9%, 28.6%, 28.3% and 35.1% in
      placebo, orlistat, sibutramine and rimonabant groups, respectively, P < 0.0001).
      In adjusted multivariable models, total attrition was significantly lower in
      groups that completed a pre-randomization lead-in period than in those that did
      not (29.1% vs. 39.9%, P < 0.01). Gender also was significantly related to total
      attrition; groups with more women had higher dropout (P < 0.01). The pattern was
      similar for predicting non-AE-related attrition. Findings suggest ways to design
      studies that maximize retention.

PMID- 19389062
TI  - Is obesity becoming a public health problem in India? Examine the shift from
      under- to overnutrition problems over time.
AB  - This study aimed to examine the prevalence and trends of overweight, obesity and
      undernutrition in recent decades in India. Based on a systematic literature
      search on PubMed and other data sources, most published studies were regional or
      local surveys in urban areas, while good representative data from the India
      National Family Health Surveys (NFHS, 1992-1993, 1998-1999 and 2005-2006) allowed
      for examining the trends at the national level. Overall, the available data
      showed that in India, prevalence of overweight was low while that of
      undernutrition remained high. Overweight was more prevalent among female, urban
      and high-socioeconomic-status (SES) groups. NFHS data showed that the prevalence
      of overweight in women and pre-school children did not increase much in the last
      decade: 10.6% and 1.6% in 1998-1999 to 12.6% and 1.5% in 2005-2006 respectively.
      As for underweight, NFHS 2005-2006 showed high prevalence among ever-married
      women (about 35%) and pre-school children (about 42%). The prevalence of
      overweight and obesity had increased slightly over the past decade in India, but
      in some urban and high-SES groups it reached a relatively high level. Factors
      associated with undernutrition need closer examination, and prevention of obesity
      should be targeted at the high-risk groups simultaneously.

PMID- 19389063
TI  - Primary cutaneous cryptococcosis in an immunocompetent host.
AB  - We report a case of primary cutaneous cryptococcosis in an immunocompetent host.
      Several nodules, isolated or sometimes joint to form plaques, affected the right
      arm. The arm was paralytic and hypoplastic, and a history of numerous abrasions
      picking firewood up preceded the onset of the eruption. Histology on skin biopsy
      documented a dermal infiltrate constituted of histiocytes, lymphocytes,
      fibroblasts and rare giant cells. Numerous rounded periodic acid-Schiff (PAS)
      bodies were also present. Cryptococcus neoformans var. neoformans grew upon
      culture. Complete blood, biochemical and instrumental examinations resulted in
      findings within normal range. Treatment with itraconazole 200 mg daily for 4
      months led to complete recovery. During a 2-year follow-up, the patient did not
      present any relapse or dissemination to other organs.

PMID- 19389064
TI  - Enzymatic characterisation of clinical isolates of Cryptococcus neoformans,
      Cryptococcus gattii and other environmental Cryptococcus spp.
AB  - This study compared the enzymatic activity of clinical isolates of Cryptococcus
      neoformans, Cryptococcus gattii, environmental isolates of C. neoformans and non
      neoformans Cryptococcus. Most of the cryptococcal isolates investigated in this
      study exhibited proteinase and phospholipase activities. Laccase activity was
      detected from all the C. neoformans and C. gattii isolates, but not from the non
      neoformans Cryptococcus isolates. There was no significant difference in the
      proteinase, phospholipase and laccase activities of C. neoformans and C. gattii.
      However, significant difference in the enzymatic activities of beta
      glucuronidase, alpha-glucosidase, beta-glucosidase and N-acetyl-beta
      glucosaminidase between C. neoformans and C. gattii isolates was observed in this
      study. Environmental isolates of C. neoformans exhibited similar enzymatic
      profiles as the clinical isolates of C. neoformans, except for lower proteinase
      and laccase activities.

PMID- 19389065
TI  - Onychomycosis in Tehran: mycological study of 504 patients.
AB  - Onychomycosis is a common nail disorder resulting from the invasion of the nail
      plate by a dermatophyte, yeast or mould species and gives rise to some diverse
      clinical presentations. The purpose of the present study was to isolate and
      identify the causative fungi of onychomycosis in the population of Tehran, Iran.
      Nail samples from 504 patients with prediagnosis of onychomycosis during 2005
      were examined both by direct microscopical observation of fungal elements in KOH
      preparations and in culture for the identification of the causative agent. All
      samples were inoculated on (i) Sabouraud dextrose agar (SDA, Merck), (ii) SDA
      with 5% chloramphenicol and cycloheximide in duplicate for dermatophyte and (iii)
      SDA with 5% chloramphenicol in triplicate for mould isolation. The criteria for
      the diagnosis of onychomycosis caused by non-dermatophytic moulds were based on
      microscopical observation of fungal elements, growth of the same mould in all
      triplicate culture and no growth of a dermatophyte or yeast in all the cultures.
      Of 504 cases examined, 216 (42.8%) were mycologically proven cases of
      onychomycosis (144 fingernails, 72 toenails). Among the positive results,
      dermatophytes were diagnosed in 46 (21.3%), yeasts in 129 (59.7%) and non
      dermatophytic moulds in 41 (19%). Trichophyton mentagrophytes was the most common
      causative agent (n = 22), followed by Trichophyton rubrum (n = 13), Candida
      albicans (n = 42), Candida spp. (n = 56) and Aspergillus spp. (n = 21). Nearly
      half of the clinically suspected fungal nail infections are onychomycosis and
      yeast is responsible for most of the infections in Iran.

PMID- 19389066
TI  - In vitro activity of voriconazole against Mexican oral yeast isolates.
AB  - Oral candidiasis is the most prevalent complication in HIV-infected and AIDS
      patients. Topical antifungal treatment is useful for the initial episodes of oral
      candidiasis, but most patients suffer more than one episode and fluconazole or
      itraconazole can help in the management, and voriconazole may represent a useful
      alternative agent for the treatment of recalcitrant oral and oesophageal
      candidiasis. The aim of this research was to study the in vitro activity of
      voriconazole and fluconazole against Mexican oral isolates of clinically relevant
      yeast. The in vitro susceptibility of 187 oral yeast isolates from HIV-infected
      and healthy Mexicans was determined for fluconazole and voriconazole by the M44-A
      disc diffusion method. At 24 h, fluconazole was active against 179 of 187
      isolates (95.7 %). Moreover, a 100% susceptibility to voriconazole was observed.
      Voriconazole and fluconazole are highly active in vitro against oral yeast
      isolates. This study provides baseline data on susceptibilities to both
      antifungal agents in Mexico.

PMID- 19389067
TI  - Antifungal susceptibility profile in vitro of Sporothrix schenckii in two growth
      phases and by two methods: microdilution and E-test.
AB  - The susceptibility profile of 91 Sporothrix schenckii isolates in both growth
      phases was determined by microdilution test (Antifungal Susceptibility Testing of
      the European Committee for Antimicrobial Susceptibility Testing; AFST-EUCAST).
      Amphotericin B (AMB), itraconazole (ITC), posaconazole, ravuconazole and
      terbinafine were found active in vitro against both phases but minimum inhibitory
      concentrations values for mycelial phase were significantly higher. Fluconazole
      (FLC) and voriconazole (VRC) were inactive in vitro against both phases. The E
      test technique was also performed with 41 representative isolates for AMB, FLC,
      ITC and VRC. Average agreement rates between yeast phase microdilution results
      and E-test results were high for AMB (77.5%) and FLC (87.8%), but low for ITC and
      VRC with rates of 56.4% and 54.5%, respectively. AFST-EUCAST is not the most
      recommended test to perform drug susceptibility testing of S. schenckii in
      clinical laboratories, and E-test could be an alternative methodology for this
      purpose, mainly when the activity in vitro of antifungal agents of AMB and FLC
      are evaluated.

PMID- 19389068
TI  - Comparative pharmacodynamic interaction analysis of triple combinations of
      caspofungin and voriconazole or ravuconazole with subinhibitory concentrations of
      amphotericin B against Aspergillus spp.
AB  - Triple combination therapy with an antifungal triazole, echinocandin and
      amphotericin B (AmB) is used in some centres to treat refractory aspergillosis.
      The objective of this study was to investigate the effect of subinhibitory
      concentrations of AmB on the double combinations of caspofungin (CAS) +
      voriconazole (VOR) or ravuconazole (RAV) against Aspergillus fumigatus,
      Aspergillus flavus and Aspergillus terreus. Isolates were studied in triplicate
      against CAS/VOR and CAS/RAV combinations by chequerboard broth microdilution. AmB
      was added to each double combination at concentrations of 0, 0.1 and 0.2 microg
      ml(-1). The fractional inhibitory concentration (FIC) index was calculated for
      the double and triple combinations. Comparative analysis was performed by
      repeated measures analysis followed by Dunnett's post-test. The double
      combinations of CAS/RAV and CAS/VOR were synergistic or additive in most
      conditions. Addition of AmB to the double combinations resulted in increased FIC
      indices for A. fumigatus and A. flavus. By contrast, AmB increased the synergism
      of the double combinations decreasing FIC indices for A. terreus (P < 0.05). RAV
      and VOR displayed similar synergistic activity with CAS. The addition of sub
      inhibitory amphotericin B concentrations reduced but did not eliminate the
      synergistic interaction between the echinocandin and triazole against A.
      fumigatus and A. flavus, while it increased the synergy against A. terreus.

PMID- 19389069
TI  - Environmental isolation of Cryptococcus neoformans and Cryptococcus gattii from
      living trees in Guindy National Park, Chennai, South India.
AB  - We report for the first time the environmental isolation of Cryptococcus
      neoformans from decaying wood and bark debris of living trees in Guindy National
      Park, Chennai, South India. Of the 40 trees screened, four isolates of
      Cryptococcus species were recovered of which two were Cryptococcus gattii, one
      was C. neoformans and one was untypable. The isolation of C. neoformans from
      Eucalyptus globulus and C. gattii from Cassia marginata in this study constitutes
      the first record of the natural occurrence of C. neoformans varieties in these
      tree species anywhere in the world. The isolation of C. gattii from Syzygium
      cumini represents the first isolation from South India.

PMID- 19389070
TI  - Invasive cutaneous infection caused by Apophysomyces elegans associated with a
      spider bite.
AB  - Cutaneous infections by Zygomycetes may have underestimated clinical
      consequences. Apophysomyces elegans is a Zygomycete that rarely causes disease in
      humans. However, it has been reported with increasing frequency in warm climate
      zones as a result of infection in healthy patients after injury to the cutaneous
      barrier. The following case report describes a 30-year-old woman with deep tissue
      involvement of A. elegans associated with a spider bite and a fatal outcome.

PMID- 19389071
TI  - Occurrence, isolation and differentiation of Candida spp. and prevalence of
      variables associated to chronic atrophic candidiasis.
AB  - The purpose of this study was to survey the frequency of Candida spp. in patients
      with chronic atrophic candidiasis (CAC), to differentiate Candida species and to
      assess the prevalence of certain infection-associated variables to this disease.
      Patients with CAC and wearing partial or complete dentures were recruited. Data
      were obtained by means of a questionnaire with details involving identification
      of the subject, demographic characteristics, behaviour and medical history,
      clinical and mycological evaluation and identification of yeast. The sample
      collection was carried out in the palate or palate and tongue of the subjects
      using sterilised swabs. Data were submitted to statistical analyses using
      Fischer's test. Forty-three (53%) cases of CAC showed the presence of Candida
      albicans. Females (75.2%) wearing complete dentures (60.1%) for more than 10
      years (58%) were risk factors to CAC development. It could be concluded that: (a)
      the results did not confirm a significant difference among patients with CAC
      concerning the presence or absence of Candida spp.; (b) the occurrence of Candida
      was negatively related to important factors associated to this opportunistic
      infection; and (c) mycological findings did not indicate that the variables
      investigated have a significant effect on oral infections by C. albicans or other
      Candida species.

PMID- 19389072
TI  - Piggyback mycosis: pulmonary hydatid cyst with a mycotic co-infection.
AB  - The lungs are common sites for the occurrence of saprophytic or invasive mycosis
      as well as hydatid cysts. The two diseases seldom coexist, and the manifestation
      is seen as a fungal ball (usually aspergilloma) formed in the cavity left behind
      after hydatid cystectomy. Active invasion and proliferation of the fungi in the
      laminated ectocyst or sometimes the pericyst of the hydatid is very unusual. We
      report such a unique coexistence identified in two of the six surgically excised
      pulmonary hydatid cysts in the past 2 years. Both were immunocompetent males, who
      had presented with non-specific symptoms of cough, haemoptysis and chest pain.
      The septate slender hyphae of the invading fungus resembled those of Aspergillus.

PMID- 19389073
TI  - Clinical, mycological and histological aspects of white onychomycosis.
AB  - Fungal leuconychia defines the clinical manifestations of white changes in
      onychomycosis. This uncommon clinical aspect is mostly seen, although not
      exclusively, in immunosuppressed patients. The principal isolated organism is
      Trichophyton spp. but the entity can also be caused by non-dermatophyte moulds.
      The mechanism of infection is unclear; it could be acquired through the proximal
      nail fold, or, as more recently proposed, may be secondary to lymphatic or
      vascular dissemination. To analyse the clinical, mycological and
      histopathological features of fungal leuconychia, we included 10 patients with
      the clinical diagnosis of fungal leuconychia. Direct examination of culture and
      nail plate biopsy were performed. Nine patients had confirmed fungal leuconychia.
      Four had a positive culture and all had positive haematoxylin-eosin (H&E) and
      Periodic Acid Schiff (PAS) stains for fungal elements with varying degrees of
      nail plate invasion. Seven of our patients were immunosuppressed and the isolated
      aetiological agents are the same as previously reported. The direct examination
      is reliable, fast and inexpensive to establish the diagnosis. The correlation of
      onychomycosis with histology, stained with H&E and PAS was 100%. We think that
      the site of nail plate invasion provides more information to support the theory
      that the infection reaches the ungual apparatus through systemic dissemination.

PMID- 19389074
TI  - The ceja-1 sequence as a potential new molecular marker for Paracoccidioides
      brasiliensis infection.
AB  - We have developed a two-step PCR assay that amplifies a region of the ceja-1
      sequence that is specific for virulent strains of Paracoccidioides brasiliensis.
      An internal region of the ceja-1 sequence was chosen for designing primers that
      were utilised in a single tube heminested PCR protocol to amplify DNA from six
      virulent strains. PCR specificity was determined by the absence of amplified
      products with genomic DNA from four non-virulent strains of P. brasiliensis and
      from eight fungal pathogens, one bacterium, two protozoa, one worm and mouse and
      human genomic DNA (leucocytes). The fact that the PCR product was only obtained
      with the genetic material from virulent isolates of P. brasiliensis suggested
      that this partial amplified sequence might be a marker of virulence for this
      fungus. The diagnostic potential of this PCR was confirmed by the successful
      amplification of this fragment with genomic DNA obtained in lymph node aspirate
      from a patient with paracoccidioidomycosis.

PMID- 19389075
TI  - Intraventricular metaplastic meningioma in a child: case report and review of the
      literature.
AB  - Childhood meningiomas are rare and display important differences from adult
      forms. We report the first case of an intraventricular metaplastic meningioma
      arising in a child. A 7-year-old female underwent resection of an enhancing tumor
      arising within the left lateral ventricle. It was composed of monomorphic cells
      embedded within an abundant myxoid stroma. The cells demonstrated epithelial
      membrane antigen and vimentin immunoreactivity. Ultrastructural analysis
      demonstrated intermediate filaments, complex intercellular interdigitations and
      desmosomes, and a diagnosis of myxoid (metaplastic) meningioma was rendered. This
      case reflects the higher incidence of intraventricular meningiomas in childhood
      and greater incidence of intraventricular meningiomas in the left lateral
      ventricle. Recognition of the grade I myxoid meningioma in this case is paramount
      since chordoid meningiomas, which share similar histologic features, are of a
      higher grade and worse prognosis.

PMID- 19389076
TI  - Prion protein oligomers in Creutzfeldt-Jakob disease detected by gel-filtration
      centrifuge columns.
AB  - Prion diseases are diagnosed by the detection of accumulation of abnormal prion
      protein (PrP) using immunohistochemistry or the detection of protease-resistant
      abnormal PrP (PrP(res)). Although the abnormal PrP is neurotoxic by forming
      aggregates, recent studies suggest that the most infectious units are smaller
      than the amyloid fibrils. In the present study, we developed a simplified method
      by applying size-exclusion gel-filtration chromatography to examine PrP oligomers
      without proteinase K digestion in Creutzfeldt-Jakob disease (CJD) samples, and
      evaluated the correlation between disease severity and the polymerization degree
      of PrP. Brain homogenates of human CJD and non-CJD cases were applied to the gel
      filtration spin columns, and fractionated PrP molecules in each fraction were
      detected by western blot. We observed that PrP oligomers could be detected by the
      simple gel-filtration method and distinctly separated from monomeric cellular PrP
      (PrP(c)). PrP oligomers were increased according to the disease severity,
      accompanied by the depletion of PrP(c). The separated PrP oligomers were already
      protease-resistant in the case with short disease duration. In the cases with
      quite severe pathology the oligomeric PrP reached a plateau, which may indicate
      that PrP molecules could mostly develop into amyloid fibrils in the advanced
      stages. The increase of PrP oligomers correlated with the degree of
      histopathological changes such as spongiosis and gliosis. The decrease of
      monomeric PrP(c) was unexpectedly obvious in the diseased cases. Dynamic changes
      of both oligomerization of the human PrP and depletion of normal PrP(c) require
      further elucidation to develop a greater understanding of the pathogenesis of
      human prion diseases.

PMID- 19389077
TI  - The first Japanese patient with variant Creutzfeldt-Jakob disease (vCJD).
AB  - Eleven years after a brief visit to some European countries, a 48-year-old
      Japanese man developed writing difficulty, irritability and general fatigue. Then
      he complained of dysesthetic pains in his legs, for which benzodiazepines were
      prescribed. However, at the time pulvinar sign was retrospectively confirmed on
      brain MRI. Eighteen months after the onset, his gait became ataxic with rapid
      deterioration of mental status over the following several months. Thirty-one
      months after the onset, he became akinetic and mute with periodic synchronous
      discharges on EEG, and died at the age of 51. The total clinical course was
      approximately 43 months. Pathological examination revealed the characteristic
      alterations of spongiform encephalopathy, severe in the thalamus, moderate but
      widely spread in the cerebral cortices, and moderate in the cerebellum. Abundant
      amyloid plaques were easily identified in the cerebral cortex and the cerebellum
      on HE staining. Immunohistochemistry for abnormal prion protein (PrP(sc))
      confirmed amyloid plaques in several forms, such as florid, uni- and multi
      centric plaques as well as perineuronal and periaxonal deposits in the basal
      ganglia and synaptic patterns in the thalami. A Western blotting study identified
      type 2B protease-resistant PrP. This is the first Japanese patient who was
      definitely diagnosed as variant Creutzfeldt-Jakob disease (vCJD). The
      pathological findings were similar to those of previous reports of vCJD in the
      UK. However, the changes were much more severe both in degree and distribution,
      probably due to a longer duration of the illness than those in the UK.

PMID- 19389078
TI  - Erythropoietin attenuates white matter damage, proinflammatory cytokine and
      chemokine induction in developing rat brain after intra-uterine infection.
AB  - To investigate the possible ameliorating effect of recombinant human
      erythropoietin (rhEPO) on white matter damage, pro-inflammatory cytokine and
      chemokine induction in developing rat brain after intra-uterine Escherichia coli
      infection. E. coli was inoculated into uterine cervix of the time-pregnant rats
      and the control was injected with normal saline. Following maternal E. coli
      inoculation, the pups received a single intraperitoneal injection of rhEPO at a
      dose of 5000 IU/kg body weight immediately after birth. Immunohistochemical
      staining and Western blot analysis for 2', 3'-cyclic nucleotide 3'
      phosphodiesterase (CNPase), neurofilament (NF) and glial fibrillary acidic
      protein (GFAP) were performed to assess white matter damage in pup brains at post
      natal day 1 (P1), P3 and P7. Pro-inflammatory cytokines and chemokines were
      detected by real-time quantitative RT-PCR at the mRNA levels to evaluate the
      inflammatory response in pup brains at P1, P3 and P7. A single dose of rhEPO
      treatment (5000 IU/kg body weight) attenuated white matter damage in developing
      rat brain after intra-uterine E. coli infection. The protein levels of CNPase and
      NF in pup brains at P7 significantly increased after post-natal rhEPO treatment
      as compared with the intra-uterine E. coli-treated group. Also, post-natal rhEPO
      injection markedly attenuated the intra-uterine E. coli infection-induced
      increases in GFAP protein expression and the mRNA levels of pro-inflammatory
      cytokines and chemokines. Post-natal EPO administration as a single dose may
      exert a neuroprotective effect on white matter damage by reducing pro
      inflammatory cytokine and chemokine induction in developing rat brain after intra
      uterine E. coli infection.

PMID- 19389079
TI  - Primary central nervous system lymphoma initially mimicking lymphomatosis
      cerebri: an autopsy case report.
AB  - A 59-year-old immunocompetent man was admitted to our hospital because of
      progressive dementia with concomitant bilateral uveitis. The first brain MRI
      revealed diffuse hyperintense lesions in the cerebral white matter of both
      hemispheres on a T2-weighted image and fluid-attenuated inversion recovery image.
      However, another MRI taken more than 1 month later revealed enhanced cohesive
      mass lesions in the bilateral thalami, in addition to the white matter lesions.
      The white matter lesions were slightly hyperintense on a diffusion-weighted image
      and apparent diffusion coefficient map image, suggesting vasogenic edema. One
      year after the onset of uveitis, he died of respiratory failure. Pathological
      diagnosis was diffuse large B-cell lymphoma with perivascular proliferation and
      diffuse scattered infiltration in the cerebrum and brainstem. Microscopically,
      cohesive mass lesions in the bilateral thalami were a massive cluster of lymphoma
      cells. This is a case of primary CNS lymphoma (PCNSL) mimicking 'lymphomatosis
      cerebri (LC)' at first but later exhibiting typical mass lesions, giving rise to
      the possibility that cases of LC might unmask features of regular lymphomas in
      their later course more often than believed thus far.

PMID- 19389080
TI  - An autopsy case of diffuse neurofibrillary tangles with calcification: early
      stage pathologic findings.
AB  - A 66-year-old man with no medically remarkable past or family history gradually
      showed personality changes, memory disturbance, sleeplessness and abnormal
      behavior. Neurologic examination showed no focal signs and neither parkinsonism
      nor cerebellar ataxia was recognized. He died 4 years after the onset of dementia
      due to chronic renal failure. Neuropathologic examination revealed neuronal loss
      and gliosis in the temporal cortex, particularly in the subiculum,
      parahippocampal gyrus and entorhinal cortex, and insular cortex. NFTs were
      observed to be widespread in the cerebral cortex, especially the temporal cortex
      and brainstem, while senile plaques were not observed. Gallyas-Braak silver
      staining revealed the presence of numerous NFTs, glial inclusions and neuropil
      threads throughout the cerebral neocortex, limbic system, hippocampus and
      brainstem. The subiculum showed the most severe involvement; severe atrophy,
      severe neuron loss, and numerous ghost tangles (extracellular NFTs) were
      apparent. Although NFTs contained both monoclonal anti-3repeat-tau antibody (RD3)
      and RD4 immunoreactivity, this differed between the intracellular NFTs and ghost
      tangles. RD3 immunoreactivity was mainly observed in ghost tangles and neuropil
      threads, whereas RD4 immunoreactivity was mainly observed in intracellular NFTs
      and glial inclusions. Calcification was also found to be widespread in the
      cerebral cortex and white matter, basal ganglia, thalamus, cerebellar cortex,
      white matter and dentate nucleus. These characteristic neuropathologic findings
      lead to the pathologic diagnosis of diffuse neurofibrillary tangles with
      calcification (DNTC). It is argued that this patient showed early stage
      pathologic signs of DNTC due to a short disease duration, which may provide clues
      regarding the progression of this rare disease.

PMID- 19389081
TI  - Evaluation of granulysin and perforin as candidate biomarkers for protection
      following vaccination with Mycobacterium bovis BCG or M. bovisDeltaRD1.
AB  - The development of improved vaccines against tuberculosis (TB) is directly linked
      to the investigation of new and better correlates of protection after vaccination
      against TB. Cloning and characterization of bovine homologues of the
      antimicrobial protein granulysin (Bo-lysin) and perforin by our group could be
      used as potential biomarkers for TB vaccination efficacy. In the present study,
      we examined the kinetics of granulysin, perforin, IFNgamma and Fas-L responses to
      Mycobacterium bovis purified protein derivative (PPD) stimulation by peripheral
      blood mononuclear cells from M. bovisDeltaRD1-, BCG- and non-vaccinated cattle.
      Gene expression profiles following PPD stimulation showed significant increases
      in transcripts for granulysin and IFNgamma in both CD4(+) and CD8(+) T cells in
      BCG-vaccinated as compared with non-vaccinated animals. Perforin and IFNgamma
      examined by flow cytometry, showed a difference of 1-2% more PPD-specific cells
      in BCG-vaccinated than non-vaccinated animals. In the vaccine trial, granulysin
      and perforin were significantly increased in both vaccine groups as compared with
      control after vaccination and challenge. IFNgamma expression was increased only
      after vaccination and secretion was higher in the control, non-protected group as
      compared with both vaccine groups demonstrating no correlation with protection
      upon vaccination. In summary, results shown here provide evidence that granulysin
      and perforin are prospective candidates as biomarkers of protection after
      vaccination against TB.

PMID- 19389082
TI  - Autophagy and the immune response to TB.
AB  - Autophagy is a homeostatic mechanism for the catabolism of cytosolic
      constituents, including organelles, in times of stress and nutrient deprivation.
      In addition, autophagy has been linked to innate and adaptive immune responses to
      numerous infectious microorganisms, including mycobacteria. This review explores
      the role of autophagy in the responses of antigen-presenting cells to
      mycobacteria, including links with phagosome maturation, inflammasome activation
      and antigen presentation. In addition, the modulation of autophagy by cytokines
      and pathogen-derived stimuli is discussed.

PMID- 19389084
TI  - Urinary calreticulin in the diagnosis of bladder urothelial carcinoma.
AB  - OBJECTIVES: To evaluate the potential suitability of calreticulin (CRT) as a
      urinary marker for bladder cancer. METHODS: Urine specimens were collected from
      patients with histologically confirmed bladder urothelial carcinoma (Group 1; n =
      109), urological patients without urothelial carcinoma (Group 2; n = 60), and non
      urological patients (Group 3; n = 40). We developed an enzyme-linked
      immunosorbent assay (ELISA) procedure using commercially available anti-CRT
      mono/polyclonal antibodies, and then measured the concentration of urinary CRT.
      RESULTS: Urinary CRT concentration of group 1 was significantly higher than group
      2 and 3 (Mann-Whitney U-test, P < 0.001). Groups 2 and 3 were joined together and
      considered as a non-bladder cancer group (n = 100), and a cutoff value (2.85
      ng/mL) was determined using receiver operating characteristic (ROC) analysis. The
      sensitivity, specificity, and the area under the curve were 67.9%, 80.0%, and
      0.742, respectively. The overall sensitivity of voided urine cytology (VUC) was
      39.0% (n = 105), and the sensitivity of urinary CRT was significantly superior to
      VUC (McNemar test, P < 0.001). Higher sensitivity was observed especially in Ta,
      G1-2, and <or=3 cm tumors. CONCLUSIONS: Urinary CRT may be useful for diagnosis
      of bladder urothelial cancer. However, given that its specificity is relatively
      low, further evaluation in larger series is needed to define its clinical
      usefulness.

PMID- 19389085
TI  - The probability of Gleason score upgrading between biopsy and radical
      prostatectomy can be accurately predicted.
AB  - The objective of this study was to test the external validity of a previously
      developed nomogram for the prediction of Gleason score upgrading (GSU) between
      biopsy and radical prostatectomy (RP). The study population consisted of 973
      assessable patients treated with RP at a tertiary care institution. The accuracy
      of the nomogram was quantified with the receiver operating characteristics curve
      derived area under the curve. The performance characteristics (predicted vs
      observed rate of GSU) were tested within a calibration plot. Overall, GSU was
      recorded in 39.8% (n = 387) of patients at RP. Of patients with GSU, 70 (18.1%),
      23 (5.9%) and 32 (8.3%), respectively, had extracapsular extension, seminal
      vesicle invasion and lymph node invasion. The accuracy of the nomogram was 74.9%
      (confidence interval 72.1-77.6%). The model tended to underestimate the observed
      rate of GSU and the discordance between the predicted and observed rate of GSU
      ranged from -7 to +10%. The current tool represents the most accurate method of
      predicting GSU between biopsy and RP. Nonetheless it is not perfect and its
      performance characteristics should be known prior to its use in clinical decision
      making.

PMID- 19389086
TI  - Triclosan: a potential allergen in suture-line allergic contact dermatitis.

PMID- 19389083
TI  - A randomized, double-blind, placebo- and propiverine-controlled trial of the
      novel antimuscarinic agent imidafenacin in Japanese patients with overactive
      bladder.
AB  - OBJECTIVES: To compare the efficacy and tolerability of imidafenacin, a novel
      antimuscarinic agent, with propiverine and a placebo in Japanese patients with
      overactive bladder (OAB). METHODS: Men and women having OAB symptoms were
      randomized to double-blind treatment with 0.1 mg of imidafenacin twice daily, 20
      mg of propiverine once daily, or a placebo for 12 weeks, and assessed for
      efficacy and safety. RESULTS: Overall, 781 patients were randomized to
      imidafenacin (324), propiverine (310), or a placebo (147). After 12 weeks of
      treatment, a significantly larger reduction in the mean number of incontinence
      episodes was observed in the imidafenacin group than in the placebo group (P <
      0.0001). The non-inferiority of imidafenacin compared with propiverine was
      confirmed for the reduction in using incontinence episodes (P = 0.0014, non
      inferiority margin: 14.5%). Imidafenacin was well tolerated. The incidence of
      adverse events with imidafenacin was significantly lower than with propiverine (P
      = 0.0101). Dry mouth, the most common adverse event, was significantly more
      common in the propiverine group than in the imidafenacin group (P = 0.0302).
      There were no significant increases in either the imidafenacin or placebo group
      in the mean QTc interval, whereas there was a significant increase in the mean
      QTc interval in the propiverine group (P < 0.0001), but there were no clinical
      arrhythmia and clinical arrhythmic events in any of the treatment groups.
      CONCLUSIONS: The novel antimuscarinic agent imidafenacin at a dose of 0.1 mg
      twice daily was not inferior to propiverine for the reduction of incontinence
      episodes, and well tolerated for the treatment of OAB symptoms.

PMID- 19389087
TI  - Bilateral type 1 complex regional pain syndrome after local nerve blocks for
      palmar hyperhidrosis.

PMID- 19389088
TI  - Poly-l-lactic acid for correction of localized facial lipoatrophy in an otherwise
      healthy young woman.

PMID- 19389089
TI  - Comparative treatment of extragenital lichen sclerosus with methylaminolevulinic
      Acid pulsed dye laser-mediated photodynamic therapy or pulsed dye laser alone.

PMID- 19389090
TI  - Surgical treatment of facial disfigurement due to lichen myxedematosus.

PMID- 19389091
TI  - The use of imiquimod to minimize the surgical defect when excising invasive
      malignant melanoma surrounded by extensive melanoma in situ, lentiginous type.

PMID- 19389092
TI  - Cutaneous leiomyosarcoma developing on a pacemaker pocket.

PMID- 19389093
TI  - Helical rim bipedicle flap.

PMID- 19389094
TI  - The purse-string lockdown.

PMID- 19389095
TI  - Bloodless nasal alar surgery: another innovative use of the chalazion clamp.

PMID- 19389096
TI  - Botulinum toxin: a treatment for compensatory hyperhidrosis in the trunk.
AB  - BACKGROUND: Severe compensatory hyperhidrosis (CH) in the trunk occurs after
      sympathectomy in some patients. Limited treatment options for these cases have
      been proposed, and the overall results have been disappointing, but injection of
      botulinum toxin-A (BTX-A) is an emerging, reliable treatment method for focal
      hyperhidrosis. OBJECTIVE: To demonstrate the efficacy, longevity, and safety of
      BTX-A injection for severe truncal sweating in CH patients who were refractory to
      conventional treatment. METHODS: Seventeen patients were injected with 100 to 500
      U of BTX-A in the truncal area. After the follow-up period, the Hyperhidrosis
      Disease Severity Scale (HDSS) for efficacy and the Dermatology Life Quality Index
      (DLQI) were measured for improvement in patients' quality of life. RESULTS: The
      baseline mean HDSS score+/-standard deviation was 3.6+/-0.5, and the sweating
      resolved within 5 days. The effect was sustained for 2 to 8 months (4.1+/-1.5
      months) and the baseline DLQI score of 9.4+/-2.0 fell to 2.8+/-1.0. No serious
      side effects or adverse events resulted from the treatment. CONCLUSIONS: BTX-A
      injection was a well-tolerated, effective, and safe method for treating severe
      truncal CH, although the considerable cost and limited duration of the treatment
      effects were major disadvantages.

PMID- 19389097
TI  - Intense pulsed light effects on the expression of extracellular matrix proteins
      and transforming growth factor beta-1 in skin dermal fibroblasts cultured within
      contracted collagen lattices.
AB  - BACKGROUND: Emerging clinical evidence suggests that intense pulsed light (IPL)
      treatment may exert some beneficial effects on photoaged skin. The molecular
      mechanisms underlying this IPL effect have not been fully elucidated. OBJECTIVE:
      To examine the effects of IPL irradiation on normal human dermal fibroblasts
      grown in contracted collagen lattices. METHODS: Human skin fibroblasts cultured
      in contracted collagen lattices were irradiated with IPL with triple pulses of 7
      ms with a pulse interval of 70 ms and fluences of 20, 50, and 75 J/cm(2). Twenty
      four hours after the irradiation, cell viability, messenger RNA (mRNA), and
      protein levels of extracellular matrix proteins (e.g., collagen I, collagen III,
      and fibronectin) and transforming growth factor beta-1 (TGF-beta1) were evaluated
      using dye exclusion, real-time reverse transcriptase polymerase chain reaction,
      and enzyme-linked immunosorbent assay, respectively. RESULTS: A dose-dependent
      increase in viable cells was demonstrated after the IPL irradiation. There was no
      significant change in mRNA levels of collagen I and fibronectin. Upregulated
      expression of collagen III and TGF-beta1 in dermal fibroblasts was verified.
      CONCLUSIONS: The analytical results presented here provide a potential
      mechanistic explanation for the mechanism of clinical photorejuvenation effects
      of IPL that involves the increase of extracellular matrix construction by
      upregulating the gene expressions of collagen III and TGF-beta1.

PMID- 19389098
TI  - Fluoroscopy-guided endovenous foam sclerotherapy using a microcatheter in
      varicose tributaries followed by endovenous laser treatment of incompetent
      saphenous veins: technical feasibility and early results.
AB  - OBJECTIVES: To evaluate the technical feasibility and preliminary results of
      endovenous foam sclerotherapy using a microcatheter in varicose tributaries
      followed by endovenous laser treatment (EVLT) of incompetent saphenous veins.
      MATERIALS AND METHODS: From July 2005 to August 2006, 312 patients (M:F=139:173,
      mean age 45.8) who presented with varicose veins with reflux in the
      saphenofemoral, saphenopopliteal junction or tributaries were enrolled. Under
      ultrasound or fluoroscopy guidance, selective microcatheterization and endovenous
      foam slcerotherapy were first performed in varicose tributaries, followed by EVLT
      (980 nm) of incompetent saphenous veins. Follow-up at 1-week and 1-, 3-, and 6
      month intervals was done. RESULTS: Technical success was seen in 410 of 411 limbs
      (99%). Continued closure of the saphenous veins and the complete sclerosis of
      varicose tributaries were noted in 332 of 373 limbs (89%) at the 1-month follow
      up, all 307 limbs (100%) at the 3-month follow-up, and all 274 limbs (100%) at
      the 6-month follow-up. No serious complication was noted. CONCLUSION: Endovenous
      foam sclerotherapy using a microcatheter in varicose tributaries followed by EVLT
      in incompetent saphenous veins is a safe, effective, and technically feasible
      treatment for varicose veins. It not only reduces additional sclerotherapy and
      technical failure, but also makes multiple therapeutic sessions unnecessary.

PMID- 19389100
TI  - Cotton dental rolls for effective and cost-efficient hemostasis.

PMID- 19389101
TI  - Surgical treatment of subungual glomus tumor: a unique and simple method.
AB  - BACKGROUND: The glomus tumor, described as a painful subcutaneous nodule,
      commonly occurs in subungual regions and is accompanied by tenderness and
      temperature sensitivity. In treatment of subungual glomus tumor, surgical
      excision is known to be the only curative method. Under surgical approach, it is
      challenging to minimize postoperative nail deformity and to reduce tumor
      recurrence. OBJECTIVE: To evaluate the efficacy and safety of surgical treatment
      of subungual glomus tumor using simple blunt dissection. MATERIALS AND METHODS:
      Twenty-three patients diagnosed with subungual glomus tumor underwent surgical
      procedure using a dorsal transungual approach. A single linear incision was made
      above the tumor, and the exposed mass was meticulously dissected with the
      opposite end of a single-end probe, and the tumor "popped up." Recurrence of
      symptom, tumor recurrence, and local complication were evaluated through long
      term follow-up. RESULTS: After a mean follow-up period of 30 months, only one
      case recurred, and partial-thickness skin necrosis occurred around the tourniquet
      site. There was no postoperative nail deformity. CONCLUSIONS: In treatment of
      subungual glomus tumor, meticulous simple blunt dissection using a transungual
      approach led the tumor to "pop up" from the tumor bed. This unique and simple
      method of treating subungual glomus tumor showed low recurrence and minimal
      complications.

PMID- 19389102
TI  - Double mucosal and myocutaneous island flap: a one-stage reconstruction for full
      thickness lower eyelid defect.
AB  - BACKGROUND: Basal cell carcinomas (BCCs) on the lower eyelid are not uncommon,
      and depending on their histological type, they can be highly aggressive and
      difficult to eradicate. Numerous techniques have been proposed for the
      reconstruction of the lower lid margin after surgical excision of the lesion.
      OBJECTIVE: To describe a double-flap technique consisting of a mucosal and
      myocutaneous V-Y advancement flap to repair full-thickness lower lid margin
      defects in a one-stage procedure under local anesthesia. METHODS: Over a 12-year
      period (1995-2007), 33 patients with BCC underwent lower eyelid reconstruction.
      After tumor excision, a triangular mucosal flap with a central pedicle was used
      to repair the inner layer. A similar triangular-shaped myocutaneous flap was
      obtained from the inferior orbicularis oculus muscle and sutured in a V-Y fashion
      to build the outer layer. RESULTS: All 33 patients achieved satisfactory
      functional and cosmetic results. Slight scleral show and discrete rounded lower
      eyelid were the main adverse effects. No additional surgery was needed.
      CONCLUSION: This double V-Y advancement flap is a simple, useful alternative
      procedure to close full-thickness defects in the lower lid margin. Aesthetic and
      functional outcome is good.

PMID- 19389104
TI  - Nonverbal hand signals: a tool for increasing patient comfort during dermatologic
      surgery.

PMID- 19389105
TI  - Fractional photothermolysis for the treatment of hypertrophic scars: clinical
      experience of eight cases.
AB  - BACKGROUND: Hypertrophic scars are common problems and represent a challenging
      condition to treat. Fractional photothermolysis has been effective at resurfacing
      photodamaged skin, acne scars, and atrophic scars, but there are few reports on
      its use for hypertrophic scars. OBJECTIVE: To evaluate the safety and efficacy of
      1,550-nm erbium-doped fiber laser treatment of hypertrophic scars in eight
      patients. METHODS: Eight patients (skin phototypes II-IV) with hypertrophic scars
      received monthly treatments with a 1,550-nm erbium-doped fiber laser. Energy
      settings ranged from 35 to 50 mJ, and eight to 10 passes were applied with
      treatment levels 6 to 8. An independent physician evaluator assessed the
      treatment response by comparing pre- and posttreatment clinical photographs using
      a quartile grading scale (grade 1, < or =25%=minimal to no improvement; grade 2,
      26-50%=moderate improvement; grade 3, 51-75%=marked improvement; grade 4,
      >75%=near total improvement. RESULTS: At four weeks after the last treatment
      session, a mean grade of 2.4 was achieved based on an independent physician's
      clinical assessment. Improvement in pigmentation occurred in all hyperpigmented
      scars. CONCLUSION: Hypertrophic scars can be effectively and safely improved with
      1,550-nm erbium-doped fiber laser treatment.

PMID- 19389106
TI  - More than 2 decades of treating atypical fibroxanthoma at mayo clinic: what have
      we learned from 91 patients?
AB  - BACKGROUND: Atypical fibroxanthoma (AFX) typically occurs on the head and neck of
      elderly white men. Usually considered a malignancy, it is treated with wide local
      excision (WLE) or total margin control using Mohs micrographic surgery (MMS).
      OBJECTIVE: To determine the most appropriate treatment for this tumor based on a
      review of cases treated at Mayo Clinic. METHODS: We reviewed the medical records
      of patients with AFX treated at Mayo Clinic from 1980 to 2004. RESULTS: We
      identified 91 patients with 93 tumors. Treatment information was available for 88
      tumors (59 treated with MMS, 23 with WLE, and 6 by other means). There were no
      recurrences in the patients treated with MMS, with a median follow-up of 4.5
      years (range 1.0-16.1 years). Two patients treated with WLE had single
      recurrences, with a median follow-up of 8.7 years (range 1.5-26.3 years).
      CONCLUSIONS: Total microscopic margin control using MMS was the most effective
      means of treating AFX.

PMID- 19389107
TI  - Adjuvant photodynamic therapy does not prevent recurrence of condylomata
      acuminata after carbon dioxide laser ablation-A phase III, prospective,
      randomized, bicentric, double-blind study.
AB  - BACKGROUND: Recurrence after therapy for anogenital warts, or condylomata
      acuminata (CA), is common. Topical photodynamic therapy (PDT) using 5
      aminolevulinic acid (ALA) is efficient in the treatment of CA, but one problem
      with PDT is the limited penetration depth of photosensitizer and light. Pre-PDT
      vaporization of CA using a carbon dioxide (CO(2)) laser may enhance efficacy.
      OBJECTIVES: CO(2) laser ablation was followed by ALA-PDT in a phase III
      prospective randomized bicenter double-blind study to prevent recurrence of CA.
      MATERIALS AND METHODS: One hundred seventy-five patients with CA received CO(2)
      laser vaporization plus adjuvant ALA-PDT (n=84) or adjuvant placebo-PDT (n=91). A
      20% ALA or placebo ointment was applied to the CA area 4 to 6 hours before CO(2)
      laser vaporization, followed by illumination with red light (600-740 nm, 100
      mW/cm(2), 100 J/cm(2)). RESULTS: Cumulative recurrence rate 12 weeks after
      treatment was 50.0% in the ALA-PDT group, versus 52.7% in the placebo-PDT group
      (p=.72). No statistically significant difference between groups was detected with
      regard to recurrence rates up to 12 months after treatment. No major
      complications were observed. CONCLUSION: Adjuvant ALA-PDT of CA after CO(2) laser
      ablation was well tolerated, but no significant difference with regard to
      recurrence rate was observed from CO(2) laser vaporization alone.

PMID- 19389108
TI  - Mohs micrographic surgery: How ACMS fellowship directors practice.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) is widely employed in the removal of
      skin cancer. As this technique becomes more widely employed, it is useful to
      establish the patterns of care provided by American College of Mohs Surgery
      (ACMS)-approved fellowship directors. OBJECTIVE: To compile and analyze data
      collected annually by the ACMS to determine practice patterns and trends in MMS
      as performed by ACMS-approved fellowship directors. MATERIALS AND METHODS: A
      retrospective study of case logs from 50 fellowship directors obtained from the
      ACMS detailing case volume, type of cancer treated, location, lesion size, wound
      size, number of stages, referral percentage, and type of repairs performed.
      RESULTS: Annual case volume per surgeon has increased linearly. The incidence of
      squamous cell carcinoma treated using MMS is rising steadily. The size of lesions
      treated using MMS has decreased slightly over several decades, as has the number
      of stages of MMS taken per lesion. The majority of MMS performed by fellowship
      directors is for skin cancer on the face. Dermatologic surgeons perform most of
      their own reconstructions. Academic and private fellowship practice patterns are
      nearly identical. CONCLUSIONS: ACMS-approved fellowship directors use MMS mainly
      for facial skin cancers, and they perform most of their own reconstructions.
      Practice patterns for most fellowship directors are similar. Private fellowships
      and academic fellowships are similar in scope and practice.

PMID- 19389109
TI  - Penetrance and clinical consequences of  a gross SDHB deletion in a large family.
AB  - Mutations in the gene encoding subunit B of the mitochondrial enzyme succinate
      dehydrogenase (SDHB) are inherited in an autosomal dominant manner and are
      associated with hereditary paraganglioma (PGL) and pheochromocytoma. The
      phenotype of patients with SDHB point mutations has been previously described.
      However, the phenotype and penetrance of gross SDHB deletions have not been well
      characterized as they are rarely described. The objective was to describe the
      phenotype and estimate the penetrance of an exon 1 large SDHB deletion in one
      kindred. A retrospective and prospective study of 41 relatives across five
      generations was carried out. The main outcome measures were genetic testing,
      clinical presentations, plasma catecholamines and their O-methylated metabolites.
      Of the 41 mutation carriers identified, 11 were diagnosed with PGL, 12 were found
      to be healthy carriers after evaluation, and 18 were reportedly healthy based on
      family history accounts. The penetrance of PGL related to the exon 1 large SDHB
      deletion in this family was estimated to be 35% by age 40. Variable expressivity
      of the phenotype associated with a large exon 1 SDHB deletion was observed,
      including low penetrance, diverse primary PGL tumor locations, and malignant
      potential.

PMID- 19389110
TI  - Adiponectin levels in adolescent girls with polycystic ovary syndrome (PCOS).
AB  - OBJECTIVE: To determine serum adiponectin concentrations in adolescent girls with
      and without polycystic ovary syndrome (PCOS) and to assess possible correlations
      of adiponectin levels with insulin and androgen levels. DESIGN: Prospective case
      control study. SETTING: Endocrine clinics in the community. PATIENTS: Forty-four
      adolescent girls were grouped as follows: 14 were overweight [body mass index
      (BMI) standard deviation score >1.645] with PCOS; 16 were lean (BMI SDS <1.036)
      with PCOS; and 14 were lean (BMI SDS <1.036) without PCOS. Intervention Blood
      samples were collected from all girls between 8 and 11 am, after an overnight
      fast. MAIN OUTCOME MEASURES: Serum levels of adiponectin, leptin, insulin,
      Mullerian-inhibiting substance, luteinizing hormone, follicle-stimulating
      hormone, testosterone, 17-alpha-hydroxyprogesterone, androstendione,
      dehydroepiandrosterone sulphate (DHEAS) and 17beta-oestradiol. RESULTS:
      Adiponectin concentrations were significantly decreased in obese adolescents with
      PCOS (10.5 +/- 5.5 mug/ml) compared with that in lean girls with or without PCOS
      (16.9 +/- 8.64 and 18.0 +/- 7.4 mug/ml respectively). Leptin levels were
      significantly elevated in obese adolescents with PCOS compared with the levels in
      normal weight adolescents with PCOS, and compared with that in normal weight
      controls. Insulin levels were markedly higher in obese adolescents with PCOS
      compared with that in normal weight adolescents (12.3 +/- 12.2 vs. 4.5 +/- 2.9, P
      < 0.05), and compared with that in normal weight PCOS adolescents (7.4 +/- 4.9);
      however, this difference was not statistically significant. Insulin levels did
      not differ between normal weight adolescents with PCOS and normal controls.
      Adiponectin concentrations correlated inversely with BMI, leptin and insulin.
      CONCLUSIONS: Hypoadiponectinaemia is evident only in obese adolescents with PCOS
      and therefore does not seem to be involved in the pathogenesis of PCOS in this
      age group.

PMID- 19389111
TI  - Allergen extract-induced interleukin-10 in human memory B cells inhibits
      immunoglobulin E production.
AB  - BACKGROUND: Elevated specific IgE antibody levels are common in atopic
      individuals, caused by T-helper type 2-dominated B cell activation. The induction
      of antigen-specific IL-10 secreting T cells is discussed as an important
      mechanism during specific immunotherapy. By contrast the presence and function of
      B cell-derived IL-10 is not well defined yet. OBJECTIVE: We investigated whether
      type-I allergen extracts induce IL-10 expression in human B cells and analysed
      its functional role on IgE production. METHODS: Human peripheral B cells were
      stimulated with grass pollen, house dust mite (HDM) (Dermatophagoides
      pteronyssimus; Der p) and dog allergen extract. Expression of IL-10 by activated
      human B cells was determined by flow cytometric analysis and ELISA. Functional
      analysis considering immunoglobulin production was assayed by ELISA. RESULTS: The
      allergen extracts studied induced IL-10 expression in B cells. However, the
      ability to induce IL-10 differed between the allergen extracts. The most potent
      allergen extract was dog (169+/-28 pg/mL), followed by grass pollen (141+/-10
      pg/mL) and HDM allergen (125+/-11 pg/mL). Upon allergen extract stimulation only
      CD27 expressing memory B cells produced IL-10 and co-expressed the very early
      activation antigen CD69. The addition of allergen extracts to B cells activated
      by anti-CD40 and IL-4 selectively inhibited IgE which was dependent on allergen
      extract-induced IL-10. By contrast the other immunoglobulin subclasses like IgA,
      IgG or IgM were not altered upon allergen extract challenge. CONCLUSION: Our data
      indicate that allergen-activated memory B cells can modulate IgE production
      through secretion of IL-10.

PMID- 19389112
TI  - Monosodium glutamate 'allergy': menace or myth?
AB  - Monosodium glutamate (MSG) is a salt form of a non-essential amino acid commonly
      used as a food additive for its unique flavour enhancing qualities. Since the
      first description of the 'Monosodium glutamate symptom complex', originally
      described in 1968 as the 'Chinese restaurant syndrome', a number of anecdotal
      reports and small clinical studies of variable quality have attributed a variety
      of symptoms to the dietary ingestion of MSG. Descriptions of MSG-induced asthma,
      urticaria, angio-oedema, and rhinitis have prompted some to suggest that MSG
      should be an aetiologic consideration in patients presenting with these
      conditions. This review prevents a critical review of the available literature
      related to the possible role of MSG in the so-called 'Chinese restaurant
      syndrome' and in eliciting asthmatic bronchospasm, urticaria, angio-oedema, and
      rhinitis. Despite concerns raised by early reports, decades of research have
      failed to demonstrate a clear and consistent relationship between MSG ingestion
      and the development of these conditions.

PMID- 19389113
TI  - Clinicovirologic analysis of hepatitis C infection in transfusion-dependent beta
      thalassemia major children.
AB  - Regular blood transfusion puts beta-thalassemia major patients at a higher risk
      of developing hepatic iron overload and hepatitis C virus (HCV) infection. The
      association between several transfusion-related factors and an increased risk of
      developing HCV viremia has been reported. The effect of HCV infection on liver
      damage in transfusion-dependent thalassemia patients has been poorly described. A
      sample of 100 Egyptian transfusion-dependent beta-thalassemia major children were
      studied. Individual patients underwent full history taking, clinical examination
      and a panel of laboratory tests including HCV ribonucleic acid polymerase chain
      reaction (HCV-PCR) in blood samples. Liver biopsy was performed for 24 patients.
      HCV-PCR was positive in 64% of patients. A statistically significant correlation
      was found between HCV-PCR positivity (HCV viremia) and shorter inter-transfusion
      interval. There was a significant positive correlation between mean serum
      ferritin level and mean levels of alanine aminotransferase and aspartase
      aminotransferase. Histopathologic features of both chronic hepatitis and
      siderosis were present in 91.7% of biopsy specimens, and fibrosis was present in
      41.67%. A higher risk of HCV viremia is noted with a shorter inter-transfusion
      interval. The reduced role of HCV infection in chronic liver injury in this group
      of patients may be surpassed by the associated effects of iron overload because
      of the chronic transfusion. However, the latter finding should be verified in
      larger studies.

PMID- 19389114
TI  - Accumulation of mitochondrial DNA damage and bioenergetic dysfunction in CSB
      defective cells.
AB  - Cockayne syndrome (CS) is a complex, progressive disease that involves
      neurological and developmental impairment and premature aging. The majority of CS
      patients have mutations in the CSB gene. The CSB protein is involved in multiple
      DNA repair pathways and CSB mutated cells are sensitive to a broad spectrum of
      genotoxic agents. We tested the hypothesis that sensitivity to such genotoxins
      could be mediated by mitochondrial dysfunction as a consequence of the CSB
      mutation. mtDNA from csb(m/m) mice accumulates oxidative damage including 8
      oxoguanine, and cells from this mouse are hypersensitive to the mitochondrial
      oxidant menadione. Inhibitors of mitochondrial complexes and the glycolysis
      inhibitor 2-deoxyglucose kill csb(m/m) cells more efficiently than wild-type
      cells, via a mechanism that does not correlate with mtDNA damage formation.
      Menadione depletes cellular ATP, and recovery after depletion is slower in
      csb(m/m) cells. The bioenergetic alteration in csb(m/m) cells parallels the
      simpler organization of supercomplexes consisting of complexes I, III and IV in
      addition to partially disassembled complex V in the inner mitochondrial membrane.
      Exposing wild-type cells to DNA intercalating agents induces complex alterations,
      suggesting a link between mtDNA integrity, respiratory complexes and
      mitochondrial function. Thus, mitochondrial dysfunction may play a role in the
      pathology of CS.

PMID- 19389115
TI  - TRB3, upregulated by ox-LDL, mediates human monocyte-derived macrophage
      apoptosis.
AB  - Tribble3 (TRB3), a mammalian homolog of Drosophila tribbles, slows cell-cycle
      progression, and its expression is increased in response to various stresses. The
      aim of this study was to investigate the role of the TRB3 gene in macrophage
      apoptosis induced by oxidized low-density lipoprotein (ox-LDL). We found that, in
      human monocyte-derived macrophages, TRB3 is upregulated by ox-LDL in a dose- and
      time-dependent manner. The cell viability of TRB3-overexpressing macrophages was
      decreased, but apoptosis was increased and the level of activated caspase-3
      increased. Factorial analyses revealed no significant interaction between TRB3
      overexpression and ox-LDL stimulation with respect to macrophage apoptosis.
      Furthermore, TRB3-silenced macrophages showed decreased apoptosis, and TRB3
      silenced cells treated with ox-LDL showed significantly increased apoptosis.
      Silencing of TRB3 and ox-LDL stimulation showed significant interaction for
      macrophage apoptosis, suggesting that TRB3 knockdown resisted the macrophage
      apoptosis induced by ox-LDL. Therefore, TRB3 in part mediates the macrophage
      apoptosis induced by ox-LDL, which suggests that TRB3 might be involved in
      vulnerable atherosclerotic plaque progression.

PMID- 19389117
TI  - Sacral dimple: incidental findings from newborn evaluation. Mucopolysaccharidosis
      IVA disease.

PMID- 19389118
TI  - Pancytopenia in a 4-year-old boy. 22q11.2 microdeletion syndrome.

PMID- 19389119
TI  - Febrile seizures.
AB  - Febrile seizures (FS) are the most common seizure disorder in childhood,
      affecting 2-5% of children between the ages of 3 and 60 months. Differentiation
      of FS from acute symptomatic seizures secondary to central nervous system
      infection is essential. Those with a focal onset, prolonged duration or which
      occur more than once within the same febrile illness are considered complex and
      have an increase in risk of subsequent epilepsy development. The vast majority of
      febrile convulsions are simple, lasting only a few minutes and without need of
      drug intervention. They have an excellent outcome with no increased risk of
      decline in IQ, subsequent epilepsy or increased mortality. Febrile seizure can
      recur, and as it often is a frightening and anxiety-provoking event for parents
      and caregivers, an understanding of the natural history and prognosis should
      enable the physician to reassure the parents providing an appropriate counselling
      and reassurance. CONCLUSION: Febrile seizure can recur, and as it often is a
      frightening and anxiety-provoking event for parent and caregivers. An
      understanding of the natural history and prognosis should enable the physician to
      reassure the parents providing an appropriate counselling and reassurance.

PMID- 19389120
TI  - Returning to play after concussion.

PMID- 19389121
TI  - Evaluation of documentation in potential abusive head injury of infants in a
      Paediatric Emergency Department.
AB  - AIM: The aim is to evaluate medical record documentation regarding potential
      abusive head injury (AHI) in infants presenting to a Paediatric Emergency
      Department (ED) with certain primary complaints known to be associated with AHI.
      METHODS: A database search was performed to find all medical records over a
      period of one year relating to those children who had one AHI-related primary
      complaint and who had had a CT head-scan performed in conjunction with admission.
      Each medical record was reviewed, in order to assess whether potential abuse had
      been investigated and documented. Each CT-scan image was re-evaluated for missed
      indications of potential injuries attributable to AHI. RESULTS: Forty-seven such
      medical records were found. Of these, 87% showed the diagnosis to be head
      injuries. The largest group of children was in the age group 0-3 months (38%). Of
      the children admitted to the Paediatric ED due to a head injury, 54% had a
      history deemed to raise suspicions of abuse but only five of them had had a
      documented investigation of child abuse. The re-evaluation of the CT-scans showed
      no missed cases. CONCLUSION: In this study we found that among children with
      known risk factors for AHI, only a few had documentation regarding potential
      child abuse. The use of a standardized protocol could be helpful in the important
      work to help staff discover potential AHI.

PMID- 19389122
TI  - Educational strategy to reduce medication errors in a neonatal intensive care
      unit.
AB  - OBJECTIVE: We aimed to evaluate the effect of a comprehensive preventive
      educational strategy on the number and type of drug errors in the prescription
      process in a regional neonatal intensive care unit (NICU). DESIGN: Medication
      errors during prescription were recorded in a 41 bed, level III regional neonatal
      unit by a pharmacist. Data were retrieved from handwritten doctor's orders and
      introduced at bedsite into an e-database. Each prescription, not related to
      enteral and parenteral nutrition and blood products, was evaluated for dosage,
      units, route and dosing interval. The study was developed in three phases: pilot
      phase to know the baseline drug error rate and estimate sample size; pre
      intervention (4182 drug orders reviewed); and post-intervention seven months
      after a comprehensive preventive educational intervention consisting sessions
      about drug errors and study's aims was implemented. RESULTS: After the preventive
      educational intervention was implemented, the prescription error rate and the
      percentage of registers with one or more incident decreased significantly from
      20.7 to 3% (p < 0.001) and from 19.2 to 2.9% (p < 0.001), respectively.
      Simultaneously, an improvement in correct identification of the prescribing
      physician was registered (from 1.3 to 78.2%). The rest of items analysed were
      similar in both periods. CONCLUSION: The implementation of a structured
      preventive educational intervention for health professionals in a regional NICU
      reduced the medication error rate, possibly by the dissemination of a patient
      safety culture.

PMID- 19389123
TI  - Foetal and congenital talipes: interventions and outcome.
AB  - AIM: Talipes is a congenital anomaly that can be corrected conservatively or
      surgically. Despite advances in management, a proportion of pregnancies still
      result in termination. We therefore aimed to establish the birth prevalence,
      interventions and outcome of talipes in our population. METHODS: Cases with
      foetal talipes were identified from the ultrasound register at the James Cook
      University Hospital between 1990 and 2006. Infants with congenital talipes
      between 1998 and 2006 were identified from the physiotherapy database. Management
      details were obtained from case records. RESULTS: A total of 46 cases with foetal
      talipes were identified among 75 933 pregnancies. Of the 34 live-born infants, 24
      (70.5%) required surgery to correct the talipes. Congenital talipes was found in
      69 infants, giving a birth prevalence of 2 per 1000 live births. Sixteen (72.7%)
      infants with an antenatal diagnosis required surgical correction. Infants with an
      antenatal diagnosis were at an increased risk of requiring surgery (relative risk
      [RR]= 1.6). CONCLUSION: Surgical management was required in more than two-thirds
      of babies with foetal talipes. Conservative management was successful in the
      majority of the babies without an antenatal diagnosis. Infants with an antenatal
      diagnosis are 1.6 times as likely to need surgical correction as infants without
      an antenatal diagnosis.

PMID- 19389128
TI  - The innate immunity role of cathepsin-D is linked to Trp-491 and Trp-492 residues
      of listeriolysin O.
AB  - Listeriolysin O (LLO) is a thiol-activated cytolysin secreted by Listeria
      monocytogenes. LLO and phosphatidylinositol phospholipase C are two essential
      virulence factors, which this bacterium needs to escape from the phagosomal
      compartment to the cytoplasm. Cathepsin-D specifically cleaves LLO, between the
      Trp-491 (tryptophan amino acid in three letter nomenclature) and Trp-492 residues
      of the conserved undecapeptide sequence, ECTGLAWEWWR, in the domain 4 of LLO
      (D4). Moreover, these residues also correspond to the phagosomal-binding epitope.
      Cathepsin-D had no effect on phosphatidylinositol phospholipase C. We have
      observed that cathepsin-D cleaved the related cholesterol-dependent cytolysin
      pneumolysin at the same undecapeptide sequence between Trp-435 and Trp-436
      residues. These studies also revealed an additional cathepsin-D cleavage site in
      the pneumolysin D4 domain localized in the 361-GDLLLD-366 sequence. These
      differences might confer a pathogenic advantage to listeriolysin O, increasing
      its resistance to phagosomal cathepsin-D action by reducing the number of
      cleavages sites in the D4 domain. Using DeltaLLO/W491A and DeltaLLO/W492A
      bacterial mutants, we reveal that the Trp-491 residue has an important role
      linked to cathepsin-D in Listeria innate immunity.

PMID- 19389129
TI  - A medical device/drug delivery system for treatment of glaucoma.
AB  - BACKGROUND: The aim of this study was to investigate the uptake and release
      kinetics of two common glaucoma drugs delivered onto hydrogel contact lenses
      using analytical chemistry and to evaluate this device's ability to control
      intraocular pressure in a limited number of volunteers. METHODS: Contact lenses
      were incubated in a source solution containing timolol maleate or brimonidine
      tartrate to determine uptake kinetics. The lenses were then immersed in fresh
      saline to determine release kinetics. Analysis was performed by high-pressure
      liquid chromatography (HPLC). HPLC column retention times were determined for
      drugs released from the lens individually and under co-elution conditions. To
      evaluate clinical feasibility and toxicity, three volunteers (patients being
      treated for glaucoma) were provided with contact lenses that had been passively
      impregnated with either drug. After a three-week wash-out period, the volunteers
      were instructed to wear the lenses for 30 minutes per day for two weeks. RESULTS:
      HPLC analysis showed that maximum uptake and release of both drugs had occurred
      by approximately 60 minutes, with the slopes tending to flatten after this point.
      The retention time on the HPLC column was 8.08 minutes for timolol maleate and
      2.16 minutes for brimonidine tartrate after incubation for one hour, with no
      changes after seven hours. Patient data showed that use of the lenses maintained
      IOP at levels equivalent to those obtained with previous treatment. No ocular
      toxicity was observed. CONCLUSION: Drugs commonly used for glaucoma treatment can
      be passively transferred to a hydrogel contact lens and then eluted from the
      polymer. Data obtained from a limited number of patients suggest that this
      contact lens/drug delivery system may be a feasible means of controlling IOP.

PMID- 19389130
TI  - When intentions go public: does social reality widen the intention-behavior gap?
AB  - Based on Lewinian goal theory in general and self-completion theory in
      particular, four experiments examined the implications of other people taking
      notice of one's identity-related behavioral intentions (e.g., the intention to
      read law periodicals regularly to reach the identity goal of becoming a lawyer).
      Identity-related behavioral intentions that had been noticed by other people were
      translated into action less intensively than those that had been ignored (Studies
      1-3). This effect was evident in the field (persistent striving over 1 week's
      time; Study 1) and in the laboratory (jumping on opportunities to act; Studies 2
      and 3), and it held among participants with strong but not weak commitment to the
      identity goal (Study 3). Study 4 showed, in addition, that when other people take
      notice of an individual's identity-related behavioral intention, this gives the
      individual a premature sense of possessing the aspired-to identity.

PMID- 19389131
TI  - Using speakers' referential intentions to model early cross-situational word
      learning.
AB  - Word learning is a "chicken and egg" problem. If a child could understand
      speakers' utterances, it would be easy to learn the meanings of individual words,
      and once a child knows what many words mean, it is easy to infer speakers'
      intended meanings. To the beginning learner, however, both individual word
      meanings and speakers' intentions are unknown. We describe a computational model
      of word learning that solves these two inference problems in parallel, rather
      than relying exclusively on either the inferred meanings of utterances or cross
      situational word-meaning associations. We tested our model using annotated corpus
      data and found that it inferred pairings between words and object concepts with
      higher precision than comparison models. Moreover, as the result of making
      probabilistic inferences about speakers' intentions, our model explains a variety
      of behavioral phenomena described in the word-learning literature. These
      phenomena include mutual exclusivity, one-trial learning, cross-situational
      learning, the role of words in object individuation, and the use of inferred
      intentions to disambiguate reference.

PMID- 19389132
TI  - Misconceptions of memory: the Scooter Libby effect.

PMID- 19389133
TI  - Avoiding groupthink: whereas weakly identified members remain silent, strongly
      identified members dissent about collective problems.

PMID- 19389134
TI  - Marital boredom now predicts less satisfaction 9 years later.

PMID- 19389135
TI  - Suppression of mutant androgen receptors by flutamide.
AB  - OBJECTIVES: To examine the effects of flutamide and hydroxyflutamide on the
      transactivation of mutant androgen receptors. METHODS: Androgen-independent human
      prostate cancer cell line PC3 was transfected with plasmids expressing wild-type,
      W741C mutant, T877A mutant or W741C+T877A mutant androgen receptors. The effects
      of bicalutamide, hydroxyflutamide or flutamide on the basal and
      dihydrotestosterone-induced transcriptional activities of the wild-type and
      mutant androgen receptors were evaluated by luciferase assays using a reporter
      plasmid containing the prostate-specific antigen (PSA) promoter. The effects of
      the antiandrogens on the transcription and translation of the PSA gene in LNCaP
      cells expressing a mutant (T877A) androgen receptor were assessed by real-time
      reverse transcription-polymerase chain reaction and radioimmunoassays. Affinity
      of the antiandrogens to each androgen receptor construct was evaluated by ligand
      binding assay. RESULTS: Flutamide, but not hydroxyflutamide, successfully
      suppressed the transcription of all of the mutant androgen receptors examined in
      this study and also showed suppressive effects on PSA secretion by LNCaP cells
      treated with dihydrotestosterone. These inhibitory effects were probably not the
      result of competitive inhibition by flutamide given its low affinity to the
      androgen receptor constructs. CONCLUSIONS: Flutamide, with its suppressive
      effects on mutant androgen receptors, may be an alternative to conventional
      antiandrogens for hormone refractory prostate cancer.

PMID- 19389136
TI  - Headache as the initial manifestation of neurocysticercosis: a case of
      eosinophilic meningitis.

PMID- 19389137
TI  - Barriers to satisfactory migraine outcomes. What have we learned, where do we
      stand?
AB  - Barriers to optimal migraine care have traditionally been divided into a number
      of categories: under-recognition and underconsultation by migraine sufferers;
      underdiagnosis and undertreatment by health care professionals; lack of follow-up
      and treatment optimization. These "traditional" barriers have been recognized and
      addressed for at least 15 years. Epidemiologic studies suggest that consultation,
      diagnosis, and treatment rates for migraine have improved although many migraine
      sufferers still do not get optimal treatment. Herein, we revisit the problem,
      review areas of progress, and expand the discussion of barriers to migraine care.
      We hypothesize that the subjective nature of pain and difficulty in communicating
      it contributes to clinical and societal barriers to care. We then revisit some of
      the traditional barriers to care, contrasting rates of recognition, diagnosis,
      and treatment over the past 15 years. We follow by addressing new barriers to
      migraine care that have emerged as a function of the knowledge gained in this
      process.

PMID- 19389138
TI  - Migraine among university students in Cotonou (Benin).
AB  - BACKGROUND: Few data are available on migraine among students in Africa. The aim
      of this study was to estimate the prevalence of migraine and describe its
      clinical features and associated conditions among students of the Faculty of
      Health Sciences of Abomey-Calavi University, in Cotonou, Benin. METHODS: A cross
      sectional study was prospectively conducted during the academic year 2002-2003
      and included 336 students selected using systematic random sampling. Migraine was
      defined according International Headache Society criteria 1988. RESULTS: The
      lifetime prevalence of migraine was 11.3% (95% CI: 8.2-15.3%). The prevalence was
      significantly higher in females (18.3%) than males (6.8%), in married-widowed
      (30.4%) than single (9.9%). The mean age at onset of the disease was 15.0 years
      +/- 2.5. Migraine without aura was the more frequent form (57.9%). The mean
      attack frequency per month was 3.8 (+/-3.4) and the peak attack duration was
      between 4 and 6 hours. Psychological tiredness was the most frequent triggering
      factors (92.1%). The factors associated with migraine in multivariate analysis
      were female sex (OR = 2.6 [95% CI: 1.2-5.3]), single marital status (OR = 3.7
      [95% CI: 1.2-11.9]) and presence of a family history of headache (OR = 2.9 [95%
      CI: 1.0-8.1]) CONCLUSION: Migraine was frequent in students in Cotonou (Benin)
      compared with other studies in Africa.

PMID- 19389139
TI  - The momentary relationship between stress and headaches in adolescent girls.
AB  - OBJECTIVE: The objective of this study was to compare the relationship between
      repeated momentary reports of stress and headaches in female adolescents with
      varying degrees of headache frequency. BACKGROUND: Headaches are the most common
      form of pain reported by adolescents affecting more than a third of all
      adolescents. High levels of stress during adolescence may predispose an
      adolescent to experience headaches in adulthood. Randomized, momentary data
      collection of stress and headaches provides the most accurate data regarding the
      adolescent experience of these variables. METHODS: The research methodology,
      ecological momentary assessment, is a valid approach to better understand the
      relationship between stress and headaches in adolescence. Data were obtained by
      each participant's use of an electronic diary (ED), which captured repeated
      momentary reports of perceived stress, head pain, and stress-related symptoms in
      female adolescents with varying degrees of recurrent headache. Seven times per
      day for the 21-day study period, teen girls responded to ED questions about their
      current stress levels, head pain, and stress-related symptoms. Based on
      participants' momentary reports of headaches, Low Headache, Moderate Headache,
      and Chronic Headache groups were created. General estimating equation models were
      used to analyze the relationship between momentary variables as well as the lag
      effect between stress and head pain. RESULTS: Thirty-one participants, aged 14-18
      years, completed 2841 randomized ED reports and reported 674 occurrences of
      headache. The Chronic Headache and Moderate Headache groups reported
      significantly increased levels of stress, head pain, and headaches. The
      relationship between momentary stress and head pain was significantly strong both
      within and across participants. The strength of this relationship increased with
      increased headache activity. A significant lag effect was found between stress
      and headaches; however, the effect of depression as a moderator of the stress and
      headache relationship remains unclear. CONCLUSION: Perceived stress and head pain
      was highly correlated in these female adolescents. Given the large population of
      teens affected by headaches, a plausible next step would be to validate these
      results in other samples and to determine methods with which to identify teens
      who may be at risk for a pattern of increasing stress and headaches.

PMID- 19389140
TI  - Ophthalmoplegia with migraine in adults: is it ophthalmoplegic migraine?
AB  - OBJECTIVE: Ophthalmoplegic migraine (OM) is a rare disorder characterized by
      recurrent oculomotor nerve palsy in children, following migraine headaches. We
      report 62 adults, seen consecutively, who developed acute ophthalmoplegia with
      severe attacks of migraine over a 10-year (1996-2005) period. An overwhelming
      majority of these patients had an antecedent worsening in severity of migraine
      headaches, before the ophthalmoplegic attack. METHODS: Sixty-two patients, aged
      15-68 years, with an acute attack of OM underwent detailed clinical, biochemical,
      and neuroradiological evaluation. RESULTS: There were 62 patients with 86 attacks
      of OM. Whereas 48 patients had a single attack, 14 had 2 or more attacks,
      fulfilling the International Headache Society criteria for probable and definite
      OM, respectively. At presentation, isolated abducens, oculomotor, and trochlear
      nerve involvements were seen in 35 (56.5%), 21 (33.9%), and 5 (8.1%) patients,
      respectively. One patient had simultaneous involvement of 3rd and 6th nerves.
      Fifty-one (82.3%) patients exhibited an antecedent worsening in severity of
      migraine, before developing ophthalmoplegia during (59/95.2%) or within 24 hours
      (3/4.8%) of a severe migraine attack, respectively. Detailed biochemistry and
      cranial neuroimaging were normal. No case had any nerve enhancement. Use of
      steroids hastened recovery (P < .05). CONCLUSION: We conclude: (1) OM in adults
      is characterized by single attacks of ophthalmoplegia in a great majority of
      patients; and (2) 6th nerve involvement occurs commonly. Our results indicate
      that moving OM to the chapter on cranial neuralgias in the second edition of the
      International Headache Classification may be premature, since nerve palsy
      occurred during a severe migraine attack in all patients.

PMID- 19389141
TI  - Vertebrate range sizes indicate that mountains may be 'higher' in the tropics.
AB  - In 1967, Daniel Janzen proposed the influential, but largely untested hypothesis,
      that tropical mountain passes are physiologically higher than temperate
      mountains. I test his key prediction, the one upon which all the others rely:
      namely, that elevational range sizes of organisms get larger on mountains at
      increasing latitudes. My analyses use 170 montane gradients spanning 36.5 degrees
      S to 48.2 degrees N latitude compiled from over 80 years of research and 16,500
      species of rodents, bats, birds, lizards, snakes, salamanders, and frogs. In
      support of Janzen's prediction, I find that elevational range size increases with
      increasing latitude for all vertebrate groups except rodents. I document
      additional lines of evidence for temperature variability as a plausible mechanism
      for trends in vertebrate range size, including strong effects of thermoregulation
      and daily temperature variability, and a weak effect of precipitation.

PMID- 19389142
TI  - Molecular physiology of the insect K-activated amino acid transporter 1 (KAAT1)
      and cation-anion activated amino acid transporter/channel 1 (CAATCH1) in the
      light of the structure of the homologous protein LeuT.
AB  - K-activated amino acid transporter 1 (KAAT1) and cation-anion-activated amino
      acid transporter/channel 1 (CAATCH1) are amino acid cotransporters, belonging to
      the Na/Cl-dependent neurotransmitter transporter family (also called SLC6/NSS),
      that have been cloned from Manduca sexta midgut. They have been thoroughly
      studied by expression in Xenopus laevis oocytes, and structure/function analyses
      have made it possible to identify the structural determinants of their cation and
      amino acid selectivity. About 40 mutants of these proteins have been studied by
      measuring amino acid uptake and current/voltage relationships. The results
      obtained since the cloning of KAAT1 and CAATCH1 are here discussed in the light
      of the 3D model of the first crystallized member of the family, the leucine
      transporter LeuT.

PMID- 19389143
TI  - EEG spectral changes underlying BOLD responses contralateral to spikes in
      patients with focal epilepsy.
AB  - PURPOSE: Simultaneous electroencephalogram and functional magnetic resonance
      imaging (EEG-fMRI) in patients with focal epilepsy and unilateral spikes often
      shows positive blood oxygenation level-dependent (BOLD) responses (activations),
      not only ipsilateral but also contralateral to the spikes. We aimed to
      investigate whether minimal EEG changes could underlie these contralateral BOLD
      responses by using EEG spectral analysis. METHODS: We studied 19 patients with
      focal epilepsy and unilateral spikes. According to the pattern of BOLD
      activation, patients were divided into Group 1 (ipsi- and contralateral to the
      spikes) or Group 2 (only ipsilateral). EEG from outside the scanner was used to
      mark spikes similar to those recorded in the scanner. Epochs of 640 ms before and
      after the peak of the spikes were chosen as baseline and spike epochs. Spectral
      analysis was performed in referential montage (FCz reference), and differences
      between baselines and spikes were analyzed by paired t-test. RESULTS: Significant
      EEG changes in electrodes contralateral to the spikes were seen in 9 of 10
      patients in Group 1 and in only 2 of 10 patients in Group 2 (one patient had two
      types of spikes that were analyzed separately). Spectral changes were seen in
      delta and/or theta bands in all patients except one (in Group 1) who had changes
      in all bands. DISCUSSION: Significant contralateral EEG changes occurred in 90%
      of contralateral BOLD activations and in only 20% of patients without
      contralateral BOLD responses. The reason why these changes predominate in lower
      frequencies rather than in higher frequencies is unclear. These spectral changes
      in areas corresponding to contralateral activations might reflect poorly
      synchronized but possibly intense neuronal activity.

PMID- 19389144
TI  - Epilepsy surgery outcomes in temporal lobe epilepsy with a normal MRI.
AB  - PURPOSE: To determine the long-term efficacy of anterior temporal lobectomy for
      medically refractory temporal lobe epilepsy in patients with nonlesional magnetic
      resonance imaging (MRI). METHODS: We identified a retrospective cohort of 44
      patients with a nonlesional modern "seizure protocol" MRI who underwent anterior
      temporal lobectomy for treatment of medically refractory partial epilepsy.
      Postoperative seizure freedom was determined by Kaplan-Meyer survival analysis.
      Noninvasive preoperative diagnostic factors potentially associated with excellent
      surgical outcome were examined by univariate analysis in the 40 patients with
      follow-up of >1 year. RESULTS: Engel class I outcomes (free of disabling
      seizures) were observed in 60% (24 of 40) patients. Preoperative factors
      associated with Engel class I outcome were: (1) absence of contralateral or
      extratemporal interictal epileptiform discharges, (2) subtraction ictal single
      photon emission computed tomography (SPECT) Coregistered to MRI (SISCOM)
      abnormality localized to the resection site, and (3) subtle nonspecific MRI
      findings in the mesial temporal lobe concordant to the resection. DISCUSSION: In
      carefully selected patients with temporal lobe epilepsy and a nonlesional MRI,
      anterior temporal lobectomy can often render patients free of disabling seizures.
      This favorable rate of surgical success is likely due to the detection of
      concordant abnormalities that indicate unilateral temporal lobe epilepsy in
      patients with nonlesional MRI.

PMID- 19389145
TI  - Guidelines for imaging infants and children with recent-onset epilepsy.
AB  - The International League Against Epilepsy (ILAE) Subcommittee for Pediatric
      Neuroimaging examined the usefulness of, and indications for, neuroimaging in the
      evaluation of children with newly diagnosed epilepsy. The retrospective and
      prospective published series with n > or = 30 utilizing computed tomography (CT)
      and magnetic resonance imaging (MRI) (1.5 T) that evaluated children with new
      onset seizure(s) were reviewed. Nearly 50% of individual imaging studies in
      children with localization-related new-onset seizure(s) were reported to be
      abnormal; 15-20% of imaging studies provided useful information on etiology or
      and seizure focus, and 2-4% provided information that potentially altered
      immediate medical management. A significant imaging abnormality in the absence of
      a history of a localization-related seizure, abnormal neurologic examination, or
      focal electroencephalography (EEG) is rare. Imaging studies in childhood absence
      epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and benign
      childhood epilepsy with centrotemporal spikes (BECTS) do not identify significant
      structural abnormalities. Imaging provides important contributions to
      establishing etiology, providing prognostic information, and directing treatment
      in children with recently diagnosed epilepsy. Imaging is recommended when
      localization-related epilepsy is known or suspected, when the epilepsy
      classification is in doubt, or when an epilepsy syndrome with remote symptomatic
      cause is suspected. When available, MRI is preferred to CT because of its
      superior resolution, versatility, and lack of radiation.

PMID- 19389146
TI  - Are the dichotomies generalized versus focal epilepsies and idiopathic versus
      symptomatic epilepsies still valid in modern epileptology?
AB  - In this commentary we discuss the basic concept of an epileptogenicity level,
      which is variable in different brain regions and is a function of multiple
      factors including the basic epileptogenicity level, routine environmental or
      internal stimuli, and various triggering and causative factors. This concept
      blurs the distinction between focal versus generalized and between idiopathic
      versus symptomatic epilepsies. We suggest dropping the dichotomy idiopathic
      versus symptomatic and to instead simply list the different etiologic factors
      that increase the epileptogenicity level. On the other hand, even if there is a
      continuum between focal and generalized epilepsies, most epilepsies are either
      predominantly focal or predominantly generalized. It is useful to maintain this
      distinction (even if somewhat artificial) because focal epilepsies can be treated
      with epilepsy surgery, and all focal epilepsies tend to respond to the same type
      of anticonvulsants. Generalized epilepsies cannot be treated surgically and
      respond to different anticonvulsants depending on the semiologic type of
      seizures.

PMID- 19389147
TI  - Mortality in captive baboons with seizures: a new model for SUDEP?
AB  - Because the baboon is a model of primary generalized epilepsy, we were interested
      in mortality of captive animals with a history of witnessed seizures. Causes of
      natural death were investigated in 46 seizure baboons (SZ) and 78 nonepileptic
      controls (CTL), all of which underwent a complete pathologic examination at the
      Southwest Foundation for Biomedical Research (SFBR) in San Antonio. SZ animals
      died at a younger age than the control baboons (p < 0.001). Almost all epileptic
      baboons that died suddenly without an apparent cause (SZ-UKN), had pulmonary
      congestion or edema without evidence of trauma, systemic illness, or heart
      disease, compared to nine controls (12%) (p < 0.001), most of which demonstrated
      evidence of a concurrent illness. Serosanguineous bronchial secretions were found
      in 15 SZ-UKN baboons (58%), but in only three controls (4%) (p < 0.001). Chronic
      multifocal fibrotic changes in myocardium were noted in only three (12%) of SZ
      UKN baboons and one control baboon. Based upon these results, untreated seizures
      appear to reduce the life expectancy of captive baboons. Sudden unexpected death
      in epilepsy (SUDEP) may be a common cause of natural death in epileptic baboons.

PMID- 19389148
TI  - An infantile-onset, severe, yet sporadic seizure pattern is common in Sturge
      Weber syndrome.
AB  - The young age of onset and frequently intractable nature of seizures associated
      with Sturge-Weber syndrome (SWS) have been well-reported in large studies.
      However, many clinicians also anecdotally describe prolonged but sporadic seizure
      clusters. Over a 5-year period, 77 children and adults with SWS and at least one
      reported seizure were referred to and evaluated at the Hunter Nelson Sturge-Weber
      Center at the Kennedy Krieger Institute. The median age of seizure onset was 6
      months with 43 (56%) presenting <1 year of age. Age at seizure onset < or = 6
      months was associated with increased hemiparesis, but not seizures. A
      characteristic pattern of clustering, intense seizures followed by prolonged
      seizure-free periods was reported in 30 (39%), but was not associated with worse
      prognosis. This seizure pattern appears to be common with SWS and leads to
      difficult treatment decisions, especially in regard to the timing of potential
      surgical resection.

PMID- 19389149
TI  - A systematic review of the epidemiology of epilepsy in Arab countries.
AB  - In this report the epidemiologic aspects of epilepsy in Arab countries are
      systematically reviewed. MEDLINE and Embase were searched, and six papers were
      identified: one incidence report from Qatar and five prevalence reports (two from
      Sudan, and one from each of Libya, Tunisia, and Saudi Arabia). An incidence of
      174 per 100,000 persons in 2001 was reported in a hospital-based study from
      Qatar. Prevalence ranged between 0.9/1,000 in Sudan and 6.5/1,000 in Saudi
      Arabia, with a median of 2.3/1,000. An approximate 724,500 people with epilepsy
      live in the Arab world. All the studies report higher prevalence in males, which
      was statistically significant in the Saudi study. The prevalence is approximately
      2-fold higher in children and young adults, compared to the rates in middle age.
      Two studies showed a high prevalence in individuals older than 60 years of age.
      Primary generalized seizures are reported in 28-97% of cases, partial seizures in
      3-43.8%, and unclassified seizures in 18-51%. Idiopathic epilepsy represents 73.5
      82.6% of cases. Early childhood brain damage such as in cerebral palsy and mental
      retardation represented a major cause of symptomatic epilepsy, whereas infection
      was the main cause in Sudan. The epidemiologic data from Arab states are lacking,
      especially from populous countries like Egypt, Algeria, and Syria. Well-designed
      studies are needed to accurately determine the burden of epilepsy in the Arab
      world.

PMID- 19389150
TI  - Persistent zinc depletion in the mossy fiber terminals in the intrahippocampal
      kainate mouse model of mesial temporal lobe epilepsy.
AB  - PURPOSE: Zinc is released in synaptic vesicles with glutamate, and modulates
      glutamatergic neurotransmission. In brain, the highest amount of zinc, detected
      by Timm staining, is in the mossy fiber (MF) system in the hippocampus. In the
      intrahippocampal kainate (KA) mouse model of mesial temporal lobe epilepsy, which
      is elicited by intrahippocampal KA, prominent MF sprouting develops rapidly
      within 2 weeks post-KA. However, the intensity of Timm staining is reduced
      gradually thereafter. The present study is designed to determine the mechanisms
      underlying this reduction of Timm staining. METHODS: The changes in Timm
      staining, and VGluT1, Synapsin-1, and zinc transporter 3 (ZnT3) immunoreactivity
      (IR) were examined from 4-56 days post-KA. An analysis of glutamate release in
      the KA-injected hippocampus was conducted by microdialysis before and during the
      continuous injection of midazolam (MDZ). RESULTS: At 56 days post-KA, Timm
      staining disappeared completely, whereas VGluT-1-, Synapsin-1-, and ZnT3-IR were
      increased in the sprouted MF boutons. However, when the seizures were suppressed
      by a continuous perfusion of MDZ, the glutamate release in the hippocampus
      decreased and Timm staining was recovered. DISCUSSION: This study showed that the
      reduction of Timm staining is the result of decreased zinc content but not the
      loss of MF itself. The reduction is the result of the enhanced release of zinc
      relative to storage, and it should facilitate the glutamate excitation that might
      be related to the epileptogenesis and rapid advancement of the morphologic
      changes in this model.

PMID- 19389151
TI  - Hippocampal distribution of vesicular glutamate transporter 1 in patients with
      temporal lobe epilepsy.
AB  - PURPOSE: Vesicular glutamate transporters (VGLUTs) are responsible for loading
      synaptic vesicles with glutamate, determining the phenotype of glutamatergic
      neurons, and have been implicated in the regulation of quantal size and
      presynaptic plasticity. We analyzed VGLUT subtype expression in normal human
      hippocampus and tested the hypothesis that alterations in VGLUT expression may
      contribute to long-term changes in glutamatergic transmission reported in
      patients with temporal lobe epilepsy (TLE). METHODS: VGLUT immunohistochemistry,
      immunofluorescence, in situ hybridization, Western blotting, and quantitative
      polymerase chain reaction (qPCR) were performed on biopsies from TLE patients
      without (non-HS) and with hippocampal sclerosis (HS) and compared to autopsy
      controls and rat hippocampus. VGLUT1 expression was compared with synaptophysin,
      neuropeptide Y (NPY), and Timm's staining. RESULTS: VGLUT1 was the predominant
      VGLUT in human hippocampus and appeared to be localized to presynaptic
      glutamatergic terminals. In non-HS hippocampi, VGLUT1 protein levels were
      increased compared to control and HS hippocampi in all subfields. In HS
      hippocampi VGLUT1 expression was decreased in subfields with severe neuronal
      loss, but strongly up-regulated in the dentate gyrus, characterized by mossy
      fiber sprouting. DISCUSSION: VGLUT1 is used as marker for glutamatergic synapses
      in the human hippocampus. In HS hippocampi VGLUT1 up-regulation in the dentate
      gyrus probably marks new glutamatergic synapses formed by mossy fiber sprouting.
      Our data indicate that non-HS patients have an increased capacity to store
      glutamate in vesicles, most likely due to an increase in translational processes
      or upregulation of VGLUT1 in synapses from afferent neurons outside the
      hippocampus. This up-regulation may increase glutamatergic transmission, and thus
      contribute to increased extracellular glutamate levels and hyperexcitability.

PMID- 19389153
TI  - Convergence in trophic morphology and feeding performance among piscivorous
      natricine snakes.
AB  - Piscivory has independently evolved numerous times amongst snakes, and therefore
      these animals provide a powerful opportunity to test for convergent evolution in
      a vertebrate feeding system. In this study, we integrate performance trials with
      comparative methods to test the hypothesis that piscivory drives convergence in
      trophic morphology and feeding performance among natricine snakes. Within and
      across species, increasing the relative length of the quadrate bone in the skull
      is positively and strongly linked to a reduction in the time needed to swallow
      large fish prey. Thus, our feeding experiments suggest that a longer quadrate
      bone enables snakes to better conform their head shape to the shape of the prey
      during swallowing. Ancestral diet reconstructions and phylogenetically corrected
      multiple regression analyses further reveal that evolutionary increases in
      piscivory are coupled to the evolution of relatively longer quadrates, and hence
      improved feeding performance on fish prey in these animals. The exploitation of
      similar dietary niches drives the evolution of convergent trophic morphologies
      and feeding performances in natricine snakes.

PMID- 19389152
TI  - The influence of concurrent anticonvulsants on the efficacy of the ketogenic
      diet.
AB  - It is unknown if any particular anticonvulsants modify the likelihood of seizure
      reduction when used in combination with the ketogenic diet (KD). A retrospective
      study was performed of 217 consecutive children who started the KD from 2000
      2007. Patients included did not have any changes to their anticonvulsant dose.
      Efficacy data at 3 months on the KD were analyzed with respect to the six most
      frequently used anticonvulsants in this cohort. A total of 115 patients were
      included. Children receiving phenobarbital in combination with the KD were
      significantly less likely to have a >50% seizure reduction (p = 0.003).
      Conversely, those receiving zonisamide in combination with the KD at onset were
      more likely to have a >50% reduction (p = 0.04). These results provide practical
      information to clinicians who are treating children receiving both the KD and
      anticonvulsants.

PMID- 19389154
TI  - Survival selection on escape performance and its underlying phenotypic traits: a
      case of many-to-one mapping.
AB  - Selection often operates not directly on phenotypic traits but on performance
      which is important as several traits may contribute to a single performance
      measure (many-to-one mapping). Although largely ignored in the context of
      selection, this asks for studies that link all relevant phenotypes with
      performance and fitness. In an enclosure experiment, we studied links between
      phenotypic traits, swimming performance and survival in two Enallagma
      damselflies. Predatory dragonflies imposed survival selection for increased
      swimming propensity and speed only in E. annexum; probably E. aspersum was
      buffered by the former species' presence. Accordingly, more circular caudal
      lamellae, structures involved in generating thrust while swimming, were selected
      for only in E. annexum. Other phenotypic traits that contributed to swimming
      speed were apparently not under selection, probably because of many-to-one
      mapping (functional redundancy). Our results indicate that not only the
      phenotypic distributions of syntopic prey organisms but also many-to-one mapping
      should be considered when documenting phenotype-performance-fitness
      relationships.

PMID- 19389155
TI  - Ecomorphometric variation and sexual dimorphism in the common shrew (Sorex
      araneus).
AB  - We investigated the evolution of the biomechanics of the mandible in island and
      mainland populations of the common shrew on the west coast of Scotland. We
      predicted that climatic differences between populations should cause differences
      in prey composition leading to changes in the mechanical potential (MP) of the
      mandible. In females, MP was correlated with climate, with greater MP in warmer
      and drier habitats. In males, MP was significantly greater than in females but
      there was no relationship between male MP and climate. This led to increased
      sexual dimorphism in colder and wetter climates. The same pattern was found after
      a phylogenetic least squares analysis was conducted to account for shared
      phylogenetic history. We discuss possible reasons for this pattern, including
      male-male combat and the greater necessity of females to feed as efficiently as
      possible to meet their extremely high energy requirements during lactation.

PMID- 19389157
TI  - Abstracts of the Canadian Conference on Medical Education (CCME). Edmonton,
      Alberta, Canada. May 2-6, 2009.

PMID- 19389161
TI  - Glacial oceanographic contrasts explain phylogeography of Australian bull kelp.
AB  - The evolutionary effects of Southern Hemisphere Pleistocene oceanographic
      conditions - marked by fluctuations in sea levels and water temperatures, and
      redirected currents - are poorly understood. The southeastern tip of Australia
      presents an intriguing model system for studying the biological impacts of
      palaeoceanography. In particular, contrasting oceanographic conditions that
      existed on eastern vs. western sides of the Bassian Isthmus during Pleistocene
      glacial periods allow for natural comparisons between putative refugial vs. re
      invading populations. Whereas many western Tasmanian marine taxa were likely
      eliminated by cold subantarctic water during the last glacial period, eastern
      Tasmanian populations would have persisted in relatively warm temperatures
      mediated by the ongoing influence of the East Australian Current (EAC). Here we
      test for the effects of contrasting palaeoceanographic conditions on endemic bull
      kelp, Durvillaea potatorum, using DNA sequence analysis (COI; rbcL) of more than
      100 individuals from 14 localities in southeastern Australia. Phylogenetic
      reconstructions reveal a deep (maximum divergence 4.7%) genetic split within D.
      potatorum, corresponding to the 'eastern' and 'western' geographical regions
      delimited by the Bassian Isthmus, a vicariant barrier during low Pleistocene sea
      levels. Concordant with the western region's cold glacial conditions, samples
      from western Tasmania and western Victoria are genetically monomorphic,
      suggesting postglacial expansion from a mainland refugium. Eastern samples, in
      contrast, comprise distinct regional haplogroups, suggesting the species
      persisted in eastern Tasmania throughout recent glacial periods. The deep east
      west divergence seems consistent with earlier reports of morphological
      differences between 'western' and 'eastern' D. potatorum, and it seems likely
      that these forms represent reproductively isolated species.

PMID- 19389159
TI  - Characterization of hadrucalcin, a peptide from Hadrurus gertschi scorpion venom
      with pharmacological activity on ryanodine receptors.
AB  - BACKGROUND AND PURPOSE: Members of the calcin family, presently including
      imperatoxin A, maurocalcin, opicalcins and hemicalcin, are basic, 33-mer peptide
      activators of ryanodine receptors (RyRs), the calcium channels of the
      sarcoplasmic reticulum (SR) that provide the majority of calcium for muscle
      contraction. Here we describe hadrucalcin, a novel member of this family.
      EXPERIMENTAL APPROACH: Hadrucalcin was isolated from the venom of Hadrurus
      gertschi. Amino acid sequence and mass were determined by Edman degradation and
      mass spectrometry respectively. A cDNA library was constructed to generate clones
      for DNA sequence determination. Biological activity of native toxin was confirmed
      with [(3)H]ryanodine binding, by using SR vesicles from cardiac and skeletal
      muscle, and with single skeletal (RyR1) and cardiac (RyR2) channels reconstituted
      in lipid bilayers. Hadrucalcin was applied to intact ventricular myocytes to
      investigate effects on calcium transients. The secondary structure of hadrucalcin
      was computer-modelled by using atomic coordinates from maurocalcin, a
      structurally similar peptide. KEY RESULTS: Hadrucalcin is distinguished from
      previously described congeners by two additional amino acids in its primary
      sequence and the lack of prominent amphipathicity. Hadrucalcin activated RyRs
      with high affinity (EC(50)= 37 nmol.L(-1)), induced a long-lasting subconductance
      state on RyR1 and RyR2, and rapidly (lag time approximately 2 s) penetrated
      ventricular cardiomyocytes, eliciting discharge of internal calcium stores and
      spontaneous contractions. CONCLUSIONS AND IMPLICATIONS: Hadrucalcin is a cell
      permeant, powerful activator of RyRs, which has translational potential for
      targeted delivery of drugs to RyR as novel therapeutic intervention in
      arrhythmogenic disease.

PMID- 19389160
TI  - Mechanisms of U46619-induced contraction of rat pulmonary arteries in the
      presence and absence of the endothelium.
AB  - BACKGROUND AND PURPOSE: Thromboxane A(2) and endothelial dysfunction are
      implicated in the development of pulmonary hypertension. The receptor
      transduction pathway for U46619 (9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy
      prostaglandin F(2 alpha))-induced contraction was examined in endothelium-intact
      (E+) and denuded (E-) rat pulmonary artery rings. EXPERIMENTAL APPROACH: Artery
      rings were mounted on a wire myograph under a tension of 7-7.5 mN at 37 degrees C
      and gassed with 95% O(2)/5% CO(2). Isometric recording was made by using Powerlab
      data collection and Chart 5 software. KEY RESULTS: Both E+ and E- contractile
      responses were sensitive to Rho-kinase inhibition and the chloride channel
      blocker NPPB [5-nitro-2-(3-phenylpropylamino)benzoic acid]. The E+ response was
      sensitive to the store-operated calcium channel blockers SKF-96365 {1-[B-[3-(4
      methoxyphenyl)propoxy]-4-methoxy-phenethyl]-1H-imidazole hydrochloride} and 2-APB
      (2-amino ethoxy diphenylborate) (75-100 micromol x L(-1)). The E- response was
      sensitive to 2-APB (10-30 micromol x L(-1)), a putative IP(3) receptor
      antagonist, and the calcium and chloride channel blockers nifedipine, DIDS (4,4'
      diisothiocyanostilbene-2,2'-disulphonic acid) and niflumic acid but was
      insensitive to SKF-96365. Inhibiting K(V) with 4-AP in E+ rings exposed a
      contraction sensitive to nifedipine, DIDS and niflumic acid, whereas inhibiting
      BK(Ca) exposed a contraction sensitive to mibefradil, DIDS and niflumic acid.
      This indicates that removal of the endothelium allows the TP receptor to inhibit
      K(V), which may involve coupling to phospholipase C, because inhibition of
      phospholipase C with U73122 (1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17
      y]amino]hexyl]- 1H-pyrrole-2,5-dione) switched the E- pathway to the E+ pathway.
      CONCLUSIONS AND IMPLICATIONS: The results from this study indicate that distinct
      transduction pathways can be employed by the TP receptor to produce contraction
      and that the endothelium is able to influence the coupling of the TP receptor.

PMID- 19389162
TI  - Multilocus heterozygosity, parental relatedness and individual fitness components
      in a wild mountain goat, Oreamnos americanus population.
AB  - Matings between relatives lead to a decrease in offspring genetic diversity which
      can reduce fitness, a phenomenon known as inbreeding depression. Because alpine
      ungulates generally live in small structured populations and often exhibit a
      polygynous mating system, they are susceptible to inbreeding. Here, we used
      marker-based measures of pairwise genetic relatedness and inbreeding to
      investigate the fitness consequences of matings between relatives in a long-term
      study population of mountain goats (Oreamnos americanus) at Caw Ridge, Alberta,
      Canada. We first assessed whether individuals avoided mating with kin by
      comparing actual and random mating pairs according to their estimated genetic
      relatedness, which was derived from 25 unlinked polymorphic microsatellite
      markers and reflected pedigree relatedness. We then examined whether individual
      multilocus heterozygosity H, used as a measure of inbreeding, was predicted by
      parental relatedness and associated with yearling survival and the annual
      probability of giving birth to a kid in adult females. Breeding pairs identified
      by genetic parentage analyses of offspring that survived to 1 year of age were
      less genetically related than expected under random matings. Parental relatedness
      was negatively correlated with offspring H, and more heterozygous yearlings had
      higher survival to 2 years of age. The probability of giving birth was not
      affected by H in adult females. Because kids that survived to yearling age were
      mainly produced by less genetically related parents, our results suggest that
      some individuals experienced inbreeding depression in early life. Future research
      will be required to quantify the levels of gene flow between different herds, and
      evaluate their effects on population genetic diversity and dynamics.

PMID- 19389163
TI  - Molecular phylogenetic biodiversity assessment of arctic and boreal
      ectomycorrhizal Lactarius Pers. (Russulales; Basidiomycota) in Alaska, based on
      soil and sporocarp DNA.
AB  - Despite the critical roles fungi play in the functioning of ecosystems,
      especially as symbionts of plants and recyclers of organic matter, their
      biodiversity is poorly known in high-latitude regions. In this paper, we discuss
      the molecular diversity of one of the most diverse and abundant groups of
      ectomycorrhizal fungi: the genus Lactarius Pers. We analysed internal transcribed
      spacer rDNA sequences from both curated sporocarp collections and soil polymerase
      chain reaction clone libraries sampled in the arctic tundra and boreal forests of
      Alaska. Our genetic diversity assessment, based on various phylogenetic methods
      and operational taxonomic unit (OTU) delimitations, suggests that the genus
      Lactarius is diverse in Alaska, with at least 43 putative phylogroups, and 24 and
      38 distinct OTUs based on 95% and 97% internal transcribed spacer sequence
      similarity, respectively. Some OTUs were identified to known species, while
      others were novel, previously unsequenced groups. Non-asymptotic species
      accumulation curves, the disparity between observed and estimated richness, and
      the high number of singleton OTUs indicated that many Lactarius species remain to
      be found and identified in Alaska. Many Lactarius taxa show strong habitat
      preference to one of the three major vegetation types in the sampled regions
      (arctic tundra, black spruce forests, and mixed birch-aspen-white spruce
      forests), as supported by statistical tests of UniFrac distances and principal
      coordinates analyses (PCoA). Together, our data robustly demonstrate great
      diversity and nonrandom ecological partitioning in an important boreal
      ectomycorrhizal genus within a relatively small geographical region. The observed
      diversity of Lactarius was much higher in either type of boreal forest than in
      the arctic tundra, supporting the widely recognized pattern of decreasing species
      richness with increasing latitude.

PMID- 19389164
TI  - Pronounced genetic diversity in tropical epiphyllous lichen fungi.
AB  - Lowland tropical habitats harbour an unexplored genetic diversity of epiphyllous
      fungi. In the shade of rainforest understoreys, lichenized fungi are specialized
      to an ephemeral habitat where they produce little vegetative biomass and develop
      reproductive structures early. In a first population genetic study of epiphyllous
      lichen fungi, we analysed the intraspecific genetic diversity of five leaf
      colonizing lichen mycobiont species. Sampling focused on a lowland perhumid
      forest plot in Costa Rica, with additional collections from other localities
      throughout the country. In all species we detected sympatric occurrence of highly
      diverged haplotypes. Haplotypes belonging to distinct clades in networks were
      also found on the same leaf, clearly indicating multiple independent colonization
      events on single leaves. Despite the unusually high genetic diversity of these
      leaf-colonizing tropical fungi, we did not detect pronounced spatial structure of
      the haplotype distribution between geographical regions. The observed patterns
      suggest that the diversity of foliicolous lichens could be much higher than
      expected, with several cryptic genetic lineages within each morphologically
      characterized species.

PMID- 19389165
TI  - Phylogeographic and demographic effects of Pleistocene climatic fluctuations in a
      montane salamander, Plethodon fourchensis.
AB  - Climatic changes associated with Pleistocene glacial cycles profoundly affected
      species distributions, patterns of interpopulation gene flow, and demography. In
      species restricted to montane habitats, ranges may expand and contract along an
      elevational gradients in response to environmental fluctuations and create high
      levels of genetic variation among populations on different mountains. The
      salamander Plethodon fourchensis is restricted to high-elevation, mesic forest on
      five montane isolates in the Ouachita Mountains. We used DNA sequence data along
      with ecological niche modelling and coalescent simulations to test several
      hypotheses related to the effects of Pleistocene climatic fluctuations on species
      in montane habitats. Our results revealed that P. fourchensis is composed of four
      well-supported, geographically structured lineages. Geographic breaks between
      lineages occurred in the vicinity of major valleys and a narrow high-elevation
      pass. Ecological niche modelling predicted that environmental conditions in
      valleys separating most mountains are suitable; however, interglacial periods
      like the present are predicted to be times of range expansion in P. fourchensis.
      Divergence dating and coalescent simulations indicated that lineage
      diversification occurred during the Middle Pleistocene via the fragmentation of a
      wide-ranging ancestor. Bayesian skyline plots showed gradual decreases in
      population size in three of four lineages over the most recent glacial period and
      a slight to moderate amount of population growth during the Holocene. Our results
      not only demonstrate that climatic changes during the Pleistocene had profound
      effects on species restricted to montane habitats, but comparison of our results
      for P. fourchensis with its parapatric, sister taxon, P. ouachitae, also
      emphasizes how responses can vary substantially even among closely related,
      similarly distributed taxa.

PMID- 19389166
TI  - Transalpine colonisation and partial phylogeographic erosion by dispersal in the
      common vole (Microtus arvalis).
AB  - The colonisation history and genetic structure of the common vole (Microtus
      arvalis) was investigated in the region of the Alps by analysing the
      mitochondrial cytochrome b gene (mtDNA) and 19 microsatellite loci (nucDNA) for
      137 voles from 52 localities. mtDNA data provided a much refined distribution of
      three highly divergent evolutionary lineages in the region compared to previous
      studies. Although high mountain ranges are widely accepted to be barriers for
      colonisation processes for many organisms and especially small terrestrial
      mammals, our phylogeographic analyses showed clear evidence of four transalpine
      colonisation events by the common vole. Individual-based phylogenetic analyses of
      nucDNA and two alternative Bayesian-clustering approaches revealed a deep genetic
      structure analogous to mtDNA. Incongruence between nucDNA and mtDNA at the
      individual level was restricted to the regions of contact between the lineages.
      mtDNA patterns and strong female philopatry in M. arvalis suggest that the
      crossings of the Alps occurred during the colonisation of the region when it was
      free from ice after the last glaciation. nucDNA patterns suggest that some of the
      transalpine elements of this phylogeographic pattern were subsequently eroded by
      male-biased gene flow. We conclude that the combination of phylogeography and
      landscape genetics at the individual level can provide very detailed insights
      into colonisation events and may even allow differentiation between historical
      and more recent processes.

PMID- 19389167
TI  - Colour variation is incongruent with mitochondrial lineages: cryptic speciation
      and subsequent diversification in a Gulf of California reef fish (Teleostei:
      Blennioidei).
AB  - The Gulf of California endemic reef fish, Acanthemblemaria crockeri (Blennioidei,
      Chaenopsidae), reportedly has two colour morphs, one with melanic lateral spots
      ('Gulf' morph) and one with orange spots ('Cape' morph). In this study, we
      recorded colour morph in both males and females and collected mitochondrial DNA
      sequence data for cytochrome c oxidase I (COI) and tRNA-Pro/D-loop of specimens
      from throughout the Gulf to explore the genetic basis of the colour morphs. Two
      highly divergent (HKY + I distance = 11.9% for COI), reciprocally monophyletic
      lineages were identified, consistent with the presence of two parapatric species.
      A 30-km gap between the distributions of mitochondrial lineages roughly
      corresponds to a hypothesized former seaway across the Baja California peninsula
      north of La Paz, although the estimated divergence time (1.84 million years ago)
      is more recent than the hypothetical seaway (3-4 million years ago).
      Surprisingly, the distribution of mitochondrial species is not congruent with the
      distribution of either male or female colour morphs. Our analysis also revealed
      significant population differentiation within both species and no shared
      haplotypes among populations. The northern Gulf species includes four populations
      (NB, CB, NM and CM) corresponding to northern and central Baja and northern and
      central mainland sites, while the Cape species includes two populations (SB and
      SM) corresponding to the Baja and mainland sides of the southern Gulf. The NB/CB
      division corresponds to a hypothesized Plio-Pleistocene mid-peninsular seaway.
      The level of genetic divergence documented in this lineage is extraordinary for a
      marine fish with a pelagic larval stage within a semi-enclosed basin.

PMID- 19389168
TI  - G(ST) is still a useful measure of genetic differentiation - a comment on Jost's
      D.

PMID- 19389171
TI  - Antagonism between local dispersal and self-incompatibility systems in a
      continuous plant population.
AB  - Many self-incompatible plant species exist in continuous populations in which
      individuals disperse locally. Local dispersal of pollen and seeds facilitates
      inbreeding because pollen pools are likely to contain relatives. Self
      incompatibility promotes outbreeding because relatives are likely to carry
      incompatible alleles. Therefore, populations can experience an antagonism between
      these forces. In this study, a novel computational model is used to explore the
      effects of this antagonism on gene flow, allelic diversity, neighbourhood sizes,
      and identity by descent. I confirm that this antagonism is sensitive to dispersal
      levels and linkage. However, the results suggest that there is little to no
      difference between the effects of gametophytic and sporophytic self
      incompatibility systems (GSI and SSI) on unlinked loci. More importantly, both
      GSI and SSI affect unlinked loci in a manner similar to obligate outcrossing
      without mating types. This suggests that the primary evolutionary impact of self
      incompatibility systems may be to prevent selfing, and prevention of biparental
      inbreeding might be a beneficial side-effect.

PMID- 19389172
TI  - A relict bank vole lineage highlights the biogeographic history of the Pyrenean
      region in Europe.
AB  - The Pyrenean region exhibits high levels of endemism suggesting a major
      contribution to the phylogeography of European species. But, to date, the role of
      the Pyrenees and surrounding areas as a glacial refugium for temperate species
      remains poorly explored. In the current study, we investigated the biogeographic
      role of the Pyrenean region through the analyses of genetic polymorphism and
      morphology of a typical forest-dwelling small mammal, the bank vole (Myodes
      glareolus). Analyses of the mitochondrial cytochrome b gene and the third upper
      molar (M(3)) show a complex phylogeographic structure in the Pyrenean region with
      at least three distinct lineages: the Western European, Spanish and Basque
      lineages. The Basque lineage in the northwestern (NW) Pyrenees was identified as
      a new clearly differentiated and geographically localized bank vole lineage in
      Europe. The average M(3) shape of Basque bank voles suggests morphological
      differentiation but also restricted genetic exchanges with other populations. Our
      genetic and morphological results as well as palaeo-environmental and fossils
      records support the hypothesis of a new glacial refugium in Europe situated in
      the NW Pyrenees. The permissive microclimatic conditions that prevailed for a
      long time in this region may have allowed the survival of temperate species,
      including humans. Moreover, local differentiation around the Pyrenees is favoured
      by the opportunity for populations to track the shift of the vegetation belt in
      altitude rather than in latitude. The finding of the Basque lineage is in
      agreement with the high level of endemic taxa reported in the NW Pyrenees.

PMID- 19389173
TI  - Is Cupressus sempervirens native in Italy? An answer from genetic and
      palaeobotanical data.
AB  - This study represents the first large-scale analysis using nuclear molecular
      markers to assess genetic diversity and structure of Cupressus sempervirens L..
      Genetic and fossil data were combined to infer the possible role of human
      activity and evolutionary history in shaping the diversity of cypress
      populations. We analysed 30 populations with six polymorphic nuclear
      microsatellite markers. Dramatic reductions in heterozygosity and allelic
      richness were observed from east to west across the species range. Structure
      analysis assigned individuals to two main groups separating central Mediterranean
      and eastern populations. The two main groups could be further divided into five
      subgroups which showed the following geographical distributions: Turkey with the
      Greek islands Rhodes and Samos, Greece (Crete), Southern Italy, Northern Italy,
      Tunisia with Central Italy. This pattern of genetic structure is also supported
      by SAMOVA and Barrier analyses. Palaeobotanical data indicated that Cupressus was
      present in Italy in the Pliocene, Pleistocene and Holocene. Furthermore, our
      molecular survey showed that Italian cypress populations experienced bottlenecks
      that resulted in reduced genetic diversity and allelic richness and greater
      genetic differentiation. Recent colonization or introduction may also have
      influenced levels of diversity detected in the Italian populations, as most
      individuals found in this range today have multilocus genotypes that are also
      present in the eastern range of the species. The data reveal a new interpretation
      of the history of cypress distribution characterized by ancient eastern
      populations (Turkey and Greek islands) and a mosaic of recently introduced trees
      and remnants of ancient, depauperate populations in the central Mediterranean
      range.

PMID- 19389174
TI  - Molecules and beyond: assessing the distinctness of the Great Lakes wolf.
AB  - The dog family, Canidae, is a widely distributed group of species that have
      evolved and radiated relatively recently into 16 genera and 36 recognized species
      (Nowak 1999). Specific taxonomic designations for some canid taxa can be unclear
      due to frequent interspecific hybridization among species in both historical and
      contemporary times, and our imperfect molecular genetic approaches for
      determining among a series of hypotheses regarding hybridization and evolution.
      In this issue of Molecular Ecology, Koblmuller et al. tackle the difficult topic
      of Great Lakes wolf taxonomy and present data that suggest this taxon is
      currently genetically distinct despite a long history of human persecution and
      hybridization with related taxa.

PMID- 19389175
TI  - A new method for estimating effective population sizes from a single sample of
      multilocus genotypes.
AB  - Equations for the effective size (N(e)) of a population were derived in terms of
      the frequencies of a pair of offspring taken at random from the population being
      sibs sharing the same one or two parents. Based on these equations, a novel
      method (called sibship assignment method) was proposed to infer N(e) from the
      sibship frequencies estimated from a sibship assignment analysis, using the
      multilocus genotypes of a sample of offspring taken at random from a single
      cohort in a population. Comparative analyses of extensive simulated data and some
      empirical data clearly demonstrated that the sibship assignment method is much
      more accurate [measured by the root mean squared error, RMSE, of 1/(2N(e))] than
      other methods such as the heterozygote excess method, the linkage disequilibrium
      method, and the temporal method. The RMSE of 1/(2N(e)) from the sibship
      assignment method is typically a small fraction of that from other methods. The
      new method is also more general and flexible than other methods. It can be
      applied to populations with nonoverlapping generations of both diploid and
      haplodiploid species under random or nonrandom mating, using either codominant or
      dominant markers. It can also be applied to the estimation of N(e) for a
      subpopulation with immigration. With some modification, it could be applied to
      monoecious diploid populations with self-fertilization, and to populations with
      overlapping generations.

PMID- 19389176
TI  - A microarray's view of life in the desert: adding a powerful evolutionary
      genomics tool to the packrat's midden.
AB  - Identifying the genetic architecture of adaptive traits is fundamental to
      understanding how organisms respond to their environment, over both ecological
      and evolutionary timeframes. Microarray technology that allows us to capture the
      simultaneous expression of thousands of genes provides unparalleled insight into
      how organisms cope with their environment at the transcriptional level. Recent
      studies in Molecular Ecology demonstrate how microarrays can rapidly identify
      which genes and pathways allow organisms to face some of the most fundamental
      physiological challenges posed by the environment, including compensation for the
      hypoxic and thermal stress of high-altitudes (Cheviron et al. 2008) and, in this
      issue, the biotransformation of toxic plant secondary compounds by mammals
      (Magnanou et al. 2009). Microarrays (Ekins et al. 1989; Fodor et al. 1991) are
      glass slides affixed with hundreds to thousands of oligonucleotide or cDNA
      sequences (probes). Messenger RNA transcripts (typically reverse transcribed to
      cDNA) are isolated from a tissue/sample of interest and hybridized to the array.
      Binding to specific probes indicates that a particular gene was transcriptionally
      active at or near the time of sampling and thus provides a potentially
      comprehensive measure of gene expression. Although a tremendously powerful tool,
      commercially produced oligonucleotide arrays are only available for a handful of
      model organisms. Nonetheless, evolutionary ecologists have exploited this
      resource by using a cross-species hybridization approach (e.g. Saetre et al.
      2004), that is, hybridizing a model organism array with a nonmodel sample (Bar-Or
      et al. 2007). Magnanou et al. (2009) present a novel example of using a model
      muroid microarray (Agilent Technologies, Rattus) to study physiological response
      in a wild, nonmodel muroid, Neotoma.

PMID- 19389177
TI  - Expression of biotransformation genes in woodrat (Neotoma) herbivores on novel
      and ancestral diets: identification of candidate genes responsible for dietary
      shifts.
AB  - The ability of herbivores to switch diets is thought to be governed by
      biotransformation enzymes. To identify potential biotransformation enzymes, we
      conducted a large-scale study on the expression of biotransformation enzymes in
      herbivorous woodrats (Neotoma lepida). We compared gene expression in a woodrat
      population from the Great Basin that feeds on the ancestral diet of juniper to
      one from the Mojave Desert that putatively switched from feeding on juniper to
      feeding on creosote. Juniper and creosote have notable differences in secondary
      chemistry, and thus, should require different biotransformation enzymes for
      detoxification. Individuals from each population were fed juniper and creosote
      diets separately. After the feeding trials, hepatic mRNA was extracted and
      hybridized to laboratory rat microarrays. Hybridization of woodrat samples to
      biotransformation probes on the array was 87%, resulting in a total of 224
      biotransformation genes that met quality control standards. Overall, we found
      large differences in expression of biotransformation genes when woodrats were fed
      juniper vs. creosote. Mojave woodrats had greater expression of 10x as many
      biotransformation genes as did Great Basin woodrats on a creosote diet. We
      identified 24 candidate genes that may be critical in the biotransformation of
      creosote toxins. Superoxide dismutase, a free radical scavenger, was also
      expressed to a greater extent by the Mojave woodrats and may be important in
      controlling oxidative damage during biotransformation. The results are consistent
      with the hypothesis that biotransformation enzymes limit diet switching and that
      woodrats in the Mojave have evolved a unique strategy for the biotransformation
      of creosote toxins.

PMID- 19389178
TI  - Parasite genetic differentiation by habitat type and host species: molecular
      epidemiology of Schistosoma japonicum in hilly and marshland areas of Anhui
      Province, China.
AB  - Schistosoma japonicum, a parasite of significant public health importance in
      parts of China and Southeast Asia, is a true generalist pathogen with over 40
      species of mammals suspected as definitive host reservoirs. In order to
      characterize levels of parasite gene flow across host species and identify the
      most important zoonotic reservoirs, S. japonicum larvae (miracidia) were sampled
      from a range of definitive host species in two contrasting habitat types within
      Anhui Province, China: a low-lying marshland region, and a hilly region, where
      animal reservoir populations may be predicted to differ substantially. Miracidia
      samples were genotyped using seven multiplexed microsatellite markers.
      Hierarchical F-statistics and clustering analyses revealed substantial
      geographical structuring of S. japonicum populations within Anhui, with strong
      parasite genetic differentiation between habitat types. Within most villages,
      there was very little or no parasite genetic differentiation among host species,
      suggesting frequent S. japonicum gene flow, and thus also transmission, across
      species. Moreover, the data provide novel molecular evidence that rodents and
      dogs are potentially very important infection reservoirs in hilly regions, in
      contrast to bovines in the marshland regions. The parasite genetic
      differentiation between habitat types might therefore be associated with
      contrasting host reservoirs. The high levels of parasite gene flow observed
      across host species in sympatric areas have important implications for S.
      japonicum control, particularly in hilly regions where control of infection among
      wild rodent populations could be challenging.

PMID- 19389179
TI  - Reticulate evolution on a mosaic of soils: diversification of the New Caledonian
      endemic genus Codia (Cunoniaceae).
AB  - We reconstructed the evolutionary history of Codia, a plant genus endemic to the
      New Caledonia biodiversity hotspot in the southwest Pacific, using three single
      copy nuclear genes. It seems likely that more than half of Codia species have a
      hybrid origin, but in the absence of cytological information, it is not known
      whether polyploids occur. Adaptation to ultramafic soils is possibly a
      plesiomorphic character for the entire genus. We found that species of hybrid
      origin can have some morphological characters absent in putative parental
      species, that is, they exhibit transgressive phenotypes. There is evidence of
      considerable range alteration post-origin in several species because some likely
      parental species of hybrid taxa no longer co-occur and are confined to putative
      rainforest refugia; in some cases, hybrid species do not now co-occur with either
      of their parental species. These results have implications for the design of
      conservation strategies, for example, prioritization of parental species for ex
      situ conservation and preservation of the contact zones between soil types where
      hybridization is more likely to occur (i.e. conserving the possibility for the
      process to continue rather than trying to conserve taxa).

PMID- 19389180
TI  - Heterologous hybridization to a complementary DNA  microarray reveals the effect
      of thermal acclimation in  the endothermic bluefin tuna (Thunnus orientalis).
AB  - The temperature stress that pelagic fishes experience can induce physiological
      and behavioural changes that leave a signature in gene expression profiles. We
      used a functional genomics approach to identify genes that were up- or down
      regulated following thermal stress in the Pacific bluefin tuna. Following the
      acclimation period, 113, 81 and 196 genes were found to be differentially
      expressed between the control (20 degrees C) and cold (15 degrees) treatment
      groups, in ventricle, red muscle and white muscle, respectively. The genes whose
      expression levels were responsive to thermal acclimation varied according to
      muscle fibre type, perhaps reflecting the tissue-specific degrees of endothermy
      characteristic of this species.

PMID- 19389181
TI  - Implications of life-history transitions on the population genetic structure of
      the toxigenic marine dinoflagellate Alexandrium tamarense.
AB  - Genotypic or phenotypic markers for characterization of natural populations of
      marine microalgae have typically addressed questions regarding differentiation
      among populations, usually with reference to a single or few clonal isolates.
      Based upon a large number of contemporaneous isolates from the same geographical
      population of the toxigenic species Alexandrium tamarense from the North Sea, we
      uncovered significant genetic substructure and low but significant multilocus
      linkage disequilibrium (LD) within the planktonic population. Between the
      alternative molecular genotyping approaches, only amplified fragment length
      polymorphism (AFLP) revealed cryptic genetic population substructure by Bayesian
      clustering, whereas microsatellite markers failed to yield concordant patterns.
      Both markers, however, gave evidence for genetic differentiation of population
      subgroups as defined by AFLP. A considerable portion of multilocus LD could be
      attributed to population subdivision. The remaining LD within population
      subgroups is interpreted as an indicator of frequency shifts of clonal lineages
      during vegetative growth of planktonic populations. Phenotypic characters such as
      cellular content and composition of neurotoxins associated with paralytic
      shellfish poisoning (PSP) and allelochemical properties may contribute to intra-
      or inter-annual differentiation of planktonic populations, if clonal lineages
      that express these characters are selectively favoured. Nevertheless, significant
      phenotypic differentiation for these characters among the genetically
      differentiated subgroups was only detected for PSP toxin content in two of the
      four population subgroups. By integrating the analysis of phenotypic and
      genotypic characteristics, we developed a conceptual population genetic model to
      explain the importance of life-cycle dynamics and transitions in the evolutionary
      ecology of these dinoflagellates.

PMID- 19389182
TI  - Understanding and treating patients with alcoholic cirrhosis: an update.
AB  - Alcoholic cirrhosis represents the terminal stage of alcoholic liver disease
      (ALD) and one of the main causes of death among alcohol abusers. The aim of this
      review was to provide an update on alcoholic cirrhosis, with an emphasis on
      recent findings. Increased alcohol consumption in developing countries is
      expected to increase cirrhosis mortality. There is a need, therefore, to develop
      new approaches to the prevention of ALD, including more attention to co-factors
      that may increase risk of ALD (i.e., obesity and diabetes, chronic HCV infection,
      and smoking). Furthermore, a better understanding of the pathological mechanisms
      on the basis of alcohol cirrhosis represents a cornerstone in order to develop
      new pharmacological treatments. Inflammatory and immune responses along with
      oxidative stress and alterations in adipokine secretion might contribute in
      different ways to the evolution of alcohol-induced fibrosis/cirrhosis. As of this
      date, patients with severe alcoholic hepatitis with a Maddrey Discriminant Factor
      (MDF) 32 should be offered pentoxifylline and/or corticosteroids unless
      contraindications exist. For ambulatory patients, S-adenosylmethionine (SAMe) may
      be considered in a motivated patient with nutritional support. Current studies do
      not support use of anti-tumor necrosis factor (TNF)-alpha antibody. Finally,
      achieving total alcohol abstinence should represent the main aim in the
      management of patients affected by any stage of cirrhosis. In the last decades,
      several drugs able to increase abstinence and prevent alcohol relapse have been
      evaluated and some of them have obtained approval for alcohol dependence.
      Patients with alcoholic cirrhosis; however, are usually excluded from such
      treatments. A recent study demonstrated the efficacy and safety of baclofen in
      inducing and maintaining alcohol abstinence in cirrhotic alcohol-dependent
      patients with cirrhosis. All together the information available suggests the need
      of a multimodal approach in the clinical management of these patients.

PMID- 19389183
TI  - High-alcohol preferring mice are more impulsive than low-alcohol preferring mice
      as measured in the delay discounting task.
AB  - BACKGROUND: Repeated studies have shown that high impulsivity, when defined as
      the tendency to choose small immediate rewards over larger delayed rewards, is
      more prevalent in drug addicts and alcoholics when compared with nonaddicts.
      Assessing whether impulsivity precedes and potentially causes addiction disorders
      is difficult in humans because they all share a history of drug use. In this
      study, we address this question by testing alcohol-naive mice from lines showing
      heritable differences in alcohol intake. METHODS: Replicated selected lines of
      outbred high-alcohol preferring (HAP) mice were compared to a low-alcohol
      preferring (LAP) line as well as the low-drinking progenitor line (HS/Ibg) on an
      adjusting amount delay discounting (DD) task. The DD task employs 2 levers to
      present subjects with a choice between a small, immediate and a large, delayed
      saccharin reward. By adjusting the quantity of the immediate reward up and down
      based on choice behavior, the task allows an estimate of how the subjective value
      of the delayed reinforcer decreases as delays increase. Latency to respond was
      also measured for each trial. RESULTS: Both HAP2 and HAP1 lines of mice were more
      impulsive than the LAP2 and HS/Ibg lines, respectively. Hyperbolic curve-fitting
      confirmed steeper discounting in the high-alcohol drinking lines. In addition,
      the high-alcohol drinking lines demonstrated greater within-session increases in
      reaction times relative to the low-alcohol drinking lines. No other differences
      (consumption of saccharin, total trials completed) consistently mapped onto
      genetic differences in alcohol drinking. CONCLUSIONS: Alcohol-naive outbred mice
      selected for high-alcohol drinking were more impulsive with saccharin reinforcers
      than low-alcohol drinkers. These data are consistent with results seen using
      inbred strain descendents of high-alcohol drinking and low-alcohol drinking rat
      lines, and suggest that impulsivity is a heritable difference that precedes
      alcoholism.

PMID- 19389184
TI  - Circadian timing of ethanol exposure exerts enduring effects on subsequent ad
      libitum consumption in C57 mice.
AB  - BACKGROUND: There is a daily rhythm in the voluntary intake of ethanol in mice,
      with greatest consumption in the early night and lowest intake during the day.
      The role of daily timing of ethanol exposure on the development and control of
      long-term ethanol self-administration has been neglected. The present study
      examines these issues using C57BL/6J mice. METHODS: Mice were repeatedly exposed
      to 10% ethanol for 2 hours early in the night or day for several weeks.
      Subsequently, ethanol was available at the opposite time (Expt 1) or 24 hours
      daily (Expts 1 and 2). Lick sensors recorded the patterns of drinking activity in
      Experiment 2. RESULTS: Mice exposed to ethanol during the night drink more than
      mice exposed during the day. Prior history did not affect ethanol intake when the
      schedule was reversed. Under 24-hour exposure conditions, mice with a history of
      drinking during the night consumed significantly more than mice drinking during
      the day. The circadian patterns of drinking were not altered. CONCLUSIONS: These
      results demonstrate that the daily timing of ethanol exposure exerts enduring
      effects of self-administration of ethanol in mice. Understanding how circadian
      rhythms regulate ethanol consumption may be valuable for modifying subsequent
      intake.

PMID- 19389185
TI  - Altered white matter integrity in adolescent binge drinkers.
AB  - BACKGROUND: White matter integrity has been found to be compromised in adult
      alcoholics, but it is unclear when in the course of alcohol exposure white matter
      abnormalities become apparent. This study assessed microstructural white matter
      integrity among adolescent binge drinkers with no history of an alcohol use
      disorder. METHODS: We used diffusion tensor imaging to examine fractional
      anisotropy (FA), a measure of directional coherence of white matter tracts, among
      teens with (n = 14) and without (n = 14) histories of binge drinking but no
      history of alcohol use disorder, matched on age, gender, and education. RESULTS:
      Binge drinkers had lower FA than controls in 18 white matter areas (clusters > or
      =27 contiguous voxels, each with p < 0.01) throughout the brain, including the
      corpus callosum, superior longitudinal fasciculus, corona radiata, internal and
      external capsules, and commissural, limbic, brainstem, and cortical projection
      fibers, while exhibiting no areas of higher FA. Among binge drinkers, lower FA in
      6 of these regions was linked to significantly greater lifetime hangover symptoms
      and/or higher estimated peak blood alcohol concentrations. CONCLUSIONS: Binge
      drinking adolescents demonstrated widespread reductions of FA in major white
      matter pathways. Although preliminary, these results could indicate that
      infrequent exposure to large doses of alcohol during youth may compromise white
      matter fiber coherence.

PMID- 19389186
TI  - Projected alcohol dose influences on the activation of alcohol expectancies in
      college drinkers.
AB  - BACKGROUND: Alcohol expectancies have been linked to drinking behavior in college
      students, and vary according to a number of factors, including projected dose of
      alcohol. Research using Multidimensional Scaling (MDS) suggests that drinking may
      be influenced by activation of differing expectancy dimensions in memory, yet
      studies have not examined expectancy activation according to projected alcohol
      doses. METHODS: The present study used Individual Differences Scaling (INDSCAL)
      to map expectancy networks of college students (n = 334) who imagined varied
      drinking at high and low alcohol doses. Expectancy activation was modeled by
      dose, as well as by gender and by drinking patterns (typical quantity, blood
      alcohol content, heavy episodic drinking, and alcohol consequences). Expectancies
      were organized along positive-negative and arousal-sedation dimensions.
      Anticipation of a high dose of alcohol was associated with greater emphasis on
      the arousal-sedation dimension, whereas anticipation of a lower dose was
      associated with greater emphasis on the positive-negative dimension. RESULTS:
      Across heavy, medium, and light drinkers, expectancy dimensions were most
      distinguishable at higher doses; activation patterns were more similar across
      drinking groups at lighter doses. Modest evidence for the influence of gender on
      activation patterns was observed. Findings were consistent across alcohol
      involvement indices. CONCLUSIONS: These data suggest that both dimensionality and
      context should be considered in the refinement of interventions designed to alter
      expectancies in order to decrease hazardous drinking.

PMID- 19389187
TI  - Effects of pregnanolone and dehydroepiandrosterone on ethanol intake in rats
      administered ethanol or saline during adolescence.
AB  - BACKGROUND: Adolescent alcohol use may contribute to long-term changes in the
      receptors and neuroactive steroids that may mediate its effects and to subsequent
      alcohol abuse and dependence as an adult. Therefore, in this study, ethanol
      preference and intake as an adult were examined after adolescent ethanol or
      saline administration. In addition, ethanol intake in the same groups was
      examined after administration of 2 neuroactive steroids with modulatory effects
      at GABA(A) receptors. METHODS: Two groups of male Long-Evans rats were
      administered 15 intraperitoneal (i.p.) injections of either ethanol (2 g/kg, 20%
      v/v) or saline between postnatal days 35 and 63. Starting on postnatal day 75,
      both groups were trained to consume 10% ethanol using a saccharin-fading
      procedure, and ethanol intake and preference were measured after a series of
      manipulations involving food deprivation, changes in the duration of access to
      ethanol, and changes in the concentrations of ethanol presented. Following these
      manipulations, pregnanolone (1 to 10 mg/kg) and dehydroepiandrosterone (DHEA, 1
      to 100 mg/kg) were administered prior to preference sessions with an 18% ethanol
      solution. RESULTS: Adult ethanol preference and intake did not differ
      significantly in subjects treated with either saline or ethanol as adolescents
      during training, the substitution of other ethanol concentrations (3.2 to 32%),
      ad-lib feeding, or moderate food deprivation. Pregnanolone administration altered
      the intake of both adolescent-treated groups after the first injection of 3.2
      mg/kg and after repeated injections with 10 mg/kg, a dose that produced sedation.
      In contrast, multiple doses of DHEA consistently decreased intake of an 18%
      ethanol concentration in both groups after repeated injections and 3 doses of
      DHEA (10, 32, and 56 mg/kg) administered with various ethanol concentrations dose
      dependently shifted the ethanol-concentration curves for the volume and dosage of
      ethanol consumed downward. CONCLUSIONS: These results indicate that chronic
      intermittent ethanol (CIE) administration of 2 g/kg during adolescence did not
      alter preference or overall consumption of ethanol in outbred rats trained to
      drink ethanol as an adult under the conditions tested, and that DHEA may be more
      effective than pregnanolone at significantly decreasing ethanol consumption.

PMID- 19389188
TI  - Decreased sensitivity to ethanol reward in adolescent mice as measured by
      conditioned place preference.
AB  - BACKGROUND: Many preclinical studies have demonstrated age-related differential
      sensitivity to various effects of ethanol between adolescent and adult animals.
      However, published data addressing possible differences in ethanol's motivational
      effects are sparse, particularly in mice. The present study examined age-related
      differences in the conditioned rewarding effects of ethanol in DBA/2J mice.
      METHODS: In the first experiment an unbiased place conditioning procedure was
      used to determine the rewarding effects of 2 g/kg ethanol in adult and adolescent
      DBA/2J mice. In a subsequent place conditioning experiment, the effects of 2 and
      4 g/kg were assessed in adolescent mice. RESULTS: Adolescents demonstrated a
      place preference with the high dose of 4 g/kg but not with a more moderate dose
      of 2 g/kg. In contrast, 2 g/kg was sufficient to produce place preference in
      adult mice. CONCLUSIONS: Adolescents are less sensitive than adults to the
      rewarding effects of ethanol but can experience reward with high doses. These
      results extend the current literature on ethanol's effects in adolescent animals.

PMID- 19389189
TI  - Ethanol teratogenesis in five inbred strains of mice.
AB  - BACKGROUND: Previous studies have demonstrated individual differences in
      susceptibility to the detrimental effects of prenatal ethanol exposure. Many
      factors, including genetic differences, have been shown to play a role in
      susceptibility and resistance, but few studies have investigated the range of
      genetic variation in rodent models. METHODS: We examined ethanol teratogenesis in
      5 inbred strains of mice: C57BL/6J (B6), Inbred Short-Sleep, C3H/Ibg, A/Ibg, and
      129S6/SvEvTac (129). Pregnant dams were intubated with either 5.8 g/kg ethanol
      (E) or an isocaloric amount of maltose-dextrin (MD) on day 9 of pregnancy. Dams
      were sacrificed on day 18 and fetuses were weighed, sexed, and examined for gross
      morphological malformations. Every other fetus within a litter was then either
      placed in Bouin's fixative for subsequent soft-tissue analyses or eviscerated and
      placed in ethanol for subsequent skeletal analyses. RESULTS: B6 mice exposed to
      ethanol in utero had fetal weight deficits and digit, kidney, brain ventricle,
      and vertebral malformations. In contrast, 129 mice showed no teratogenesis. The
      remaining strains showed varying degrees of teratogenesis. CONCLUSIONS:
      Differences among inbred strains demonstrate genetic variation in the teratogenic
      effects of ethanol. Identifying susceptible and resistant strains allows future
      studies to elucidate the genetic architecture underlying prenatal alcohol
      phenotypes.

PMID- 19389190
TI  - IgA immune responses against acetaldehyde adducts and biomarkers of alcohol
      consumption in patients with IgA glomerulonephritis.
AB  - BACKGROUND: The pathogenesis of IgA glomerulonephritis (IgAGN) involves intense
      deposition of IgAs within the glomerulus. Although previous studies have shown
      that heavy drinking frequently leads to the generation of IgA antibodies against
      neo-antigens induced by ethanol metabolites and tissue deposition of IgAs, the
      associations between alcohol consumption, IgA immune responses, and kidney
      disease have not been examined. METHODS: A total of 158 IgAGN patients (96 men,
      62 women) were classified as abstainers (n = 38), moderate drinkers (n = 114),
      and heavy drinkers (n = 6) based on self-reported alcohol consumption. The
      reference population included 143 individuals (99 men, 44 women) who were either
      apparently healthy abstainers (n = 31), moderate drinkers (n = 43), or heavy
      drinkers devoid of liver disease (n = 69). The assessments included various
      biomarkers of alcohol consumption: carbohydrate-deficient transferrin (CDT),
      glutamyl transferase, gamma-CDT (combination of GGR and CDT), mean corpuscular
      volume (MCV), tests for liver and kidney function, serum immunoglobulin A (IgA),
      and specific IgA antibodies against acetaldehyde-protein adducts. RESULTS: In
      male IgAGN patients, drinking status was significantly associated with MCV, p <
      0.001; CDT, p < 0.01; and gamma -CDT, p < 0.05. In the reference population, all
      biomarkers and anti-adduct IgA levels were found to vary according to drinking
      status. In IgAGN patients, anti-adduct IgA levels were elevated in 63% of the
      cases but the titers did not associate with self-reported ethanol intake.
      CONCLUSIONS: These data indicate high levels of IgA antibodies against
      acetaldehyde-derived antigens in IgAGN patients, which may hamper the use of the
      immune responses as markers of alcohol consumption among such patients. Future
      studies on the pathogenic and prognostic significance of anti-adduct immune
      responses in IgAGN patients are warranted.

PMID- 19389192
TI  - The impact of underage drinking laws on alcohol-related fatal crashes of young
      drivers.
AB  - BACKGROUND: This study used a pre- to post-design to evaluate the influence on
      drinking-and-driving fatal crashes of 6 laws directed at youth aged 20 and
      younger and 4 laws targeting all drivers. METHODS: Data on the laws were drawn
      from the Alcohol Policy Information System data set (1998 to 2005), the Digests
      of State Alcohol Highway Safety Related Legislation (1983 to 2006), and the
      Westlaw database. The Fatality Analysis Reporting System data set (1982 to 2004)
      was used to assess the ratio of drinking to nondrinking drivers involved in fatal
      crashes [fatal crash incidence ratio (CIR)]. The data were analyzed using
      structural equation modeling techniques. RESULTS: Significant decreases in the
      underage fatal CIR were associated with presence of 4 of the laws targeting youth
      (possession, purchase, use and lose, and zero tolerance) and 3 of the laws
      targeting all drivers (0.08 blood alcohol concentration illegal per se law,
      secondary or upgrade to a primary seat belt law, and an administrative license
      revocation law). Beer consumption was associated with a significant increase in
      the underage fatal CIR. The direct effects of laws targeting drivers of all ages
      on adult drinking drivers aged 26 and older were similar but of a smaller
      magnitude compared to the findings for those aged 20 and younger. It is estimated
      that the 2 core underage drinking laws (purchase and possession) and the zero
      tolerance law are currently saving an estimated 732 lives per year controlling
      for other exposure factors. If all states adopted use and lose laws, an
      additional 165 lives could be saved annually. CONCLUSIONS: These results provide
      substantial support for the effectiveness of under age 21 drinking laws with 4 of
      the 6 laws examined having significant associations with reductions in underage
      drinking-and-driving fatal crashes. These findings point to the importance of key
      underage drinking and traffic safety laws in efforts to reduce underage drinking
      driver crashes.

PMID- 19389191
TI  - Nitric oxide-mediated intestinal injury is required for alcohol-induced gut
      leakiness and liver damage.
AB  - BACKGROUND: Alcoholic liver disease (ALD) requires endotoxemia and is commonly
      associated with intestinal barrier leakiness. Using monolayers of intestinal
      epithelial cells as an in vitro barrier model, we showed that ethanol-induced
      intestinal barrier disruption is mediated by inducible nitric oxide synthase
      (iNOS) upregulation, nitric oxide (NO) overproduction, and oxidation/nitration of
      cytoskeletal proteins. We hypothesized that iNOS inhibitors [NG-nitro-l-arginine
      methyl ester (l-NAME), l-N(6)-(1-iminoethyl)-lysine (l-NIL)] in vivo will inhibit
      the above cascade and liver injury in an animal model of alcoholic
      steatohepatitis (ASH). METHODS: Male Sprague-Dawley rats were gavaged daily with
      alcohol (6 g/kg/d) or dextrose for 10 weeks +/- l-NAME, l-NIL, or vehicle.
      Systemic and intestinal NO levels were measured by nitrites and nitrates in urine
      and tissue samples, oxidative damage to the intestinal mucosa by protein carbonyl
      and nitrotyrosine, intestinal permeability by urinary sugar tests, and liver
      injury by histological inflammation scores, liver fat, and myeloperoxidase
      activity. RESULTS: Alcohol caused tissue oxidation, gut leakiness, endotoxemia,
      and ASH. l-NIL and l-NAME, but not the d-enantiomers, attenuated all steps in the
      alcohol-induced cascade including NO overproduction, oxidative tissue damage, gut
      leakiness, endotoxemia, hepatic inflammation, and liver injury. CONCLUSIONS: The
      mechanism we reported for alcohol-induced intestinal barrier disruption in vitro 
      NO overproduction, oxidative tissue damage, leaky gut, endotoxemia, and liver
      injury - appears to be relevant in vivo in an animal model of alcohol-induced
      liver injury. That iNOS inhibitors attenuated all steps of this cascade suggests
      that prevention of this cascade in alcoholics will protect the liver against the
      injurious effects of chronic alcohol and that iNOS may be a useful target for
      prevention of ALD.

PMID- 19389193
TI  - Proopiomelanocortin peptides are not essential for development of ethanol-induced
      behavioral sensitization.
AB  - BACKGROUND: Behavioral sensitization is a result of neuroadaptation to repeated
      drug administration and is hypothesized to reflect an increased susceptibility to
      drug abuse. Proopiomelanocortin (POMC) derived peptides including beta-endorphin
      and alpha-melanocyte stimulating hormone have been implicated in development of
      behavioral sensitization and the reinforcing effects of alcohol and other drugs
      of abuse. This study used a genetically engineered mouse strain that is deficient
      for neural POMC to directly determine if any POMC peptides are necessary for the
      development of ethanol-induced locomotor sensitization. METHODS: Adult female
      mice deficient for POMC in neurons only (Pomc(-/-)Tg/Tg, KO) and wildtype
      (Pomc(+/+)Tg/Tg, WT) littermates were injected once daily with either saline or
      ethanol (i.p.) for 12 to 13 days. On ethanol test day (day 13 or 14) all mice
      from both treatment groups received an i.p. injection of ethanol immediately
      before a 15-minute analysis of locomotor activity. Blood ethanol concentration
      (BEC) was measured on ethanol test day immediately following the test session.
      Baseline locomotor activity was measured for 15 minutes after a saline injection
      2 days later in both groups. RESULTS: There was no significant difference in BEC
      between genotypes (WT = 2.11 +/- 0.06; KO = 2.03 +/- 0.08 mg/ml). Both WT and
      nPOMC-deficient mice treated repeatedly with ethanol demonstrated a significant
      increase in locomotor activity on test day when compared to repeated saline
      treated counterparts. In addition, mice of both genotypes in the repeated saline
      groups showed a significant locomotor stimulant response to acute ethanol
      injection. CONCLUSIONS: Central POMC peptides are not required for either the
      acute locomotor stimulatory effect of ethanol or the development of ethanol
      induced locomotor sensitization. While these peptides may modulate other ethanol
      associated behaviors, they are not essential for development of behavioral
      sensitization.

PMID- 19389194
TI  - N-acetylcysteine improves group B streptococcus clearance in a rat model of
      chronic ethanol ingestion.
AB  - BACKGROUND: Sepsis is the most common risk factor associated with acute
      respiratory distress syndrome (ARDS) and results in a 40-60% mortality rate due
      to respiratory failure. Furthermore, recent epidemiological studies have
      demonstrated that a history of alcohol abuse increases the risk of ARDS by 3.6
      fold. More recently, group B streptococcus (GBS) infections in nonpregnant adults
      have been increasing, particularly in alcoholics where there is an increased risk
      of lobular invasion and mortality. We have shown in an established rat model that
      chronic ethanol ingestion impaired macrophage internalization of inactivated
      infectious particles in vitro and enhanced bidirectional protein flux across the
      alveolar epithelial-endothelial barriers, both of which were attenuated when
      glutathione precursors were added to the diet. We hypothesized that chronic
      ethanol ingestion would increase the risk of infection even though GBS is less
      pathogenic but that dietary N-acetylcysteine (NAC), a glutathione precursor,
      would improve in vivo clearance of infectious particles and reduce systemic
      infection. METHODS: After 6 weeks of ethanol feeding, rats were given GBS
      intratracheally and sacrificed 24 hours later. GBS colony-forming units were
      counted in the lung, liver, spleen, and bronchoalveolar lavage fluid. Acute lung
      injury in response to GBS was also assessed. RESULTS: Chronic ethanol exposure
      decreased GBS clearance from the lung indicating an active lung infection. In
      addition, increased colonies formed within the liver and spleen indicated that
      ethanol increased the risk of systemic infection. Ethanol also exacerbated the
      acute lung injury induced by GBS. NAC supplementation normalized GBS clearance by
      the lung, prevented the appearance of GBS systemically, and attenuated acute lung
      injury. CONCLUSIONS: These data suggested that chronic alcohol ingestion
      increased the susceptibility of the lung to bacterial infections from GBS as well
      as systemic infections. Furthermore, dietary NAC improved in vivo clearance of
      GBS particles, attenuated acute lung injury, and disseminated infection.

PMID- 19389196
TI  - Protective effect of vitamin E against ethanol-induced hyperhomocysteinemia, DNA
      damage, and atrophy in the developing male rat brain.
AB  - BACKGROUND: Chronic alcoholism leads to elevated plasma and brain homocysteine
      (Hcy) levels, as demonstrated by clinical investigations and animal experiments.
      It has been posited that elevated levels of Hcy mediate DNA damage, brain
      atrophy, and excitotoxicity. The current study sought to elucidate the effect of
      vitamin E on ethanol-induced hyperhomocysteinemia, DNA damage, and atrophy in the
      developing hippocampus and cerebellum of rats. METHODS: Pregnant Wistar rats
      received ethanol with or without vitamin E from gestation day 7 throughout
      lactation. Weight changes in the brain, hippocampus and cerebellum, DNA damage,
      and Hcy levels in the plasma, hippocampus, and cerebellum of male offspring were
      measured at the end of lactation. RESULTS: The results revealed that along with a
      significant decrease in brain, cerebellum, and hippocampus weights in animals
      that received alcohol, the levels of DNA damage and Hcy significantly increased.
      Significant amelioration of brain atrophy and DNA damage as well as restoration
      of the elevated level of Hcy to that of controls were found in vitamin E-treated
      rats. CONCLUSIONS: These findings strongly support the idea that ethanol intake
      by dams during pregnancy and lactation induces Hcy-mediated oxidative stress in
      the developing hippocampus and cerebellum of offspring rats, and that these
      effects can be alleviated by vitamin E as an antioxidant.

PMID- 19389195
TI  - Disparity between tonic and phasic ethanol-induced dopamine increases in the
      nucleus accumbens of rats.
AB  - BACKGROUND: Dopamine concentrations in the nucleus accumbens fluctuate on phasic
      (subsecond) and tonic (over minutes) timescales in awake rats. Acute ethanol
      increases tonic concentrations of dopamine, but its effect on subsecond dopamine
      transients has not been fully explored. METHODS: We measured tonic and phasic
      dopamine fluctuations in the nucleus accumbens of rats in response to ethanol
      (within-subject cumulative dosing, 0.125 to 2 g/kg, i.v.). RESULTS: Microdialysis
      samples yielded significant tonic increases in dopamine concentrations at 1 to 2
      g/kg ethanol in each rat, while repeated saline infusions had no effect. When
      monitored with fast scan cyclic voltammetry, ethanol increased the frequency of
      dopamine transients in 6 of 16 recording sites, in contrast to the uniform effect
      of ethanol as measured with microdialysis. In the remaining 10 recording sites
      that were unresponsive to ethanol, dopamine transients either decreased in
      frequency or were unaffected by cumulative ethanol infusions, patterns also
      observed during repeated saline infusions. The responsiveness of particular
      recording sites to ethanol was not correlated with either core versus shell
      placement of the electrodes or the basal rate of dopamine transients.
      Importantly, the phasic response pattern to a single dose of ethanol at a
      particular site was qualitatively reproduced when a second dose of ethanol was
      administered, suggesting that the variable between-site effects reflected
      specific pharmacology at that recording site. CONCLUSIONS: These data demonstrate
      that the relatively uniform dopamine concentrations obtained with microdialysis
      can mask a dramatic heterogeneity of phasic dopamine release within the
      accumbens.

PMID- 19389197
TI  - Mitochondrial S-adenosyl-L-methionine transport is insensitive to alcohol
      mediated changes in membrane dynamics.
AB  - BACKGROUND: Alcohol-induced liver injury is associated with decreased S-adenosyl
      l-methionine (SAM)/S-adenosyl-l-homocysteine (SAH) ratio and mitochondrial
      glutathione (mGSH) depletion, which has been shown to sensitize hepatocytes to
      tumor necrosis factor (TNF). AIMS: As the effect of alcohol on mitochondrial SAM
      (mSAM) has been poorly characterized, our aim was to examine the status and
      transport of mSAM in relation to that of mGSH during alcohol intake. METHODS:
      Sprague-Dawley rats were pair fed Lieber-DeCarli diets containing alcohol for 1
      to 4 weeks and liver fractionated into cytosol and mitochondria to examine the
      mSAM transport and its sensitivity to membrane dynamics. RESULTS: We found that
      cytosol SAM was depleted from the first week of alcohol feeding, with mSAM levels
      paralleling these changes. Cytosol SAH, however, increased during the first 3
      weeks of alcohol intake, whereas its mitochondrial levels remained unchanged.
      mGSH depletion occurred by 3 to 4 weeks of alcohol intake due to cholesterol
      mediated impaired transport from the cytosol. In contrast to this outcome, the
      transport of SAM into hepatic mitochondria was unaffected by alcohol intake and
      resistant to cholesterol-mediated perturbations in membrane dynamics; furthermore
      cytosolic SAH accumulation in primary hepatocytes by SAH hydrolase inhibition
      reproduced the mSAM depletion by alcohol due to the competition of SAH with SAM
      for mitochondrial transport. However, alcohol feeding did not potentiate the
      sensitivity to inhibition by SAH accumulation. CONCLUSIONS: Alcohol-induced mSAM
      depletion precedes that of mGSH and occurs independently of alcohol-mediated
      perturbations in membrane dynamics, disproving an inherent defect in the mSAM
      transport by alcohol. These findings suggest that the early mSAM depletion may
      contribute to the alterations of mitochondrial membrane dynamics and the
      subsequent mGSH down-regulation induced by alcohol feeding.

PMID- 19389198
TI  - Facilitation of myocardial PI3K/Akt/nNOS signaling contributes to ethanol-evoked
      hypotension in female rats.
AB  - BACKGROUND: The mechanism by which ethanol reduces cardiac output (CO) and blood
      pressure (BP) in female rats remains unclear. We tested the hypothesis that
      enhancement of myocardial phosphatidylinositol 3-kinase (PI3K)/Akt signaling and
      related neuronal nitric oxide synthase (nNOS) and/or endothelial nitric oxide
      synthase (eNOS) activity constitutes a cellular mechanism for the hemodynamic
      effects of ethanol. METHODS: We measured the level of phosphorylated eNOS (p
      eNOS) and p-nNOS in the myocardium of ethanol (1 g/kg intragastric, i.g.) treated
      female rats along with hemodynamic responses [BP, CO, stroke volume, (SV), total
      peripheral resistance, (TPR)], and myocardial nitrate/nitrite levels (NOx)
      levels. Further, we investigated the effect of selective pharmacological
      inhibition of nNOS with N(omega)-propyl-l-arginine (NPLA) or eNOS with N(5)-(1
      iminoethyl)-l-ornithine (l-NIO) on cellular, hemodynamic, and biochemical effects
      of ethanol. The effects of PI3K inhibition by wortmannin on the cardiovascular
      actions of ethanol and myocardial Akt phosphorylation were also investigated.
      RESULTS: The hemodynamic effects of ethanol (reductions in BP, CO, and SV) were
      associated with significant increases in myocardial NOx and myocardial p-nNOS and
      p-Akt expressions while myocardial p-eNOS remained unchanged. Prior nNOS
      inhibition by NPLA (2.5 or 12.5 microg/kg) attenuated hemodynamic effects of
      ethanol and abrogated associated increases in myocardial NOx and cardiac p-nNOS
      contents. The hemodynamic effects of ethanol and increases in myocardial p-Akt
      phosphorylation were reduced by wortmannin (15 microg/kg). On the other hand,
      although eNOS inhibition by l-NIO (4 or 20 mg/kg) in a dose-dependent manner
      attenuated ethanol-evoked hypotension, the concomitant reductions in CO and SV
      remained unaltered. Also, selective eNOS inhibition uncovered dramatic increases
      in TPR in response to ethanol, which appeared to have offset the reduction in CO.
      Neither NPLA nor l-NIO altered plasma ethanol levels. CONCLUSIONS: These findings
      implicate the myocardial PI3K/Akt/nNOS signaling in the reductions in BP and CO
      produced by ethanol in female rats.

PMID- 19389199
TI  - The glycine reuptake inhibitor org 25935 interacts with basal and ethanol-induced
      dopamine release in rat nucleus accumbens.
AB  - BACKGROUND: The mesolimbic dopamine (DA) projection from the ventral tegmental
      area to nucleus accumbens (nAc), a central part of the reward system, is
      activated by ethanol (EtOH) and other drugs of abuse. We have previously
      demonstrated that the glycine receptor in the nAc and its amino acid agonists may
      be implicated in the DA activation and reinforcing properties of EtOH. We have
      also reported that the glycine transporter 1 inhibitor, Org 25935, produces a
      robust and dose-dependent decrease in EtOH consumption in Wistar rats. The
      present study explores the interaction between EtOH and Org 25935 with respect to
      DA levels in the rat nAc. METHODS: The effects of Org 25935 (6 mg/kg, i.p.)
      and/or EtOH (2.5 g/kg, i.p.) on accumbal DA levels were examined by means of in
      vivo microdialysis (coupled to HPLC-ED) in freely moving male Wistar rats. The
      effect of Org 25935 on accumbal glycine output was also investigated. RESULTS:
      Systemic Org 25935 increased DA output in a subpopulation of rats (52% in
      Experiment 1 and 38% in Experiment 2). In Experiment 2, EtOH produced a
      significant increase in DA levels in vehicles (35%) and in Org 25935
      nonresponders (19%), whereas EtOH did not further increase the DA level in rats
      responding to Org 25935 (2%). The same dose of Org 25935 increased glycine levels
      by 87% in nAc. CONCLUSIONS: This study demonstrates that Org 25935, probably via
      increased glycine levels, (i) counteracts EtOH-induced increases of accumbal DA
      levels and (ii) increases basal DA levels in a subpopulation of rats. The results
      are in line with previous findings and it is suggested that the effects observed
      involve interference with accumbal GlyRs and are related to the alcohol
      consumption modulating effect of Org 25935.

PMID- 19389200
TI  - Factor structure and concurrent validity of the obsessive compulsive drinking
      scale in a group of alcohol-dependent subjects of Mexico City.
AB  - BACKGROUND: Obsessive thoughts and compulsive drinking behaviors have been
      proposed as key factors associated with the loss of control over alcohol
      consumption experienced by alcohol-dependent patients. The self-report 14-item
      Obsessive Compulsive Drinking Scale (OCDS; Anton et al., 1995) was designed in
      order to rate these features. METHODS: A Spanish-translated version of the OCDS
      was applied to a group of 159 alcohol-dependent subjects while in abstinence, and
      data were analyzed in order to evaluate the factor structure and concurrent
      validity of the scale. RESULTS: Several solutions were explored after applying
      the principal factor analysis to the data. The most plausible result was obtained
      after excluding the items on quantity and frequency of drinking. This model
      explaining 56.9% of the variance included 2 factors: obsessive thoughts related
      to drinking and interference/behaviors related to drinking. Additionally, OCDS
      scores were significantly correlated with measures for the Alcohol Dependence
      Scale, number of DSM-IV criteria met for alcohol dependence as well as the number
      of days in a week engaged in heavy drinking, indicating concurrent validity.
      CONCLUSIONS: Our results support the use of OCDS as a valid self-rated instrument
      that can be broadly applied in research and treatment settings. However, its
      current version includes questions that may not represent the core concept of
      craving. The abridged 12-item version of the scale (excluding the items on
      drinking habits) maintains good psychometrics features and seems to be adequate
      when different cognitive and behavioral dimensions are explored.

PMID- 19389202
TI  - CONSORT comes to TRANSFUSION.

PMID- 19389201
TI  - Sizing up ethanol-induced plasticity: the role of small and large conductance
      calcium-activated potassium channels.
AB  - Small (SK) and large conductance (BK) Ca(2+)-activated K(+) channels contribute
      to action potential repolarization, shape dendritic Ca(2+)spikes and postsynaptic
      responses, modulate the release of hormones and neurotransmitters, and contribute
      to hippocampal-dependent synaptic plasticity. Over the last decade, SK and BK
      channels have emerged as important targets for the development of acute ethanol
      tolerance and for altering neuronal excitability following chronic ethanol
      consumption. In this mini-review, we discuss new evidence implicating SK and BK
      channels in ethanol tolerance and ethanol-associated homeostatic plasticity.
      Findings from recent reports demonstrate that chronic ethanol produces a
      reduction in the function of SK channels in VTA dopaminergic and CA1 pyramidal
      neurons. It is hypothesized that the reduction in SK channel function increases
      the propensity for burst firing in VTA neurons and increases the likelihood for
      aberrant hyperexcitability during ethanol withdrawal in hippocampus. There is
      also increasing evidence supporting the idea that ethanol sensitivity of native
      BK channel results from differences in BK subunit composition, the proteolipid
      microenvironment, and molecular determinants of the channel-forming subunit
      itself. Moreover, these molecular entities play a substantial role in controlling
      the temporal component of ethanol-associated neuroadaptations in BK channels.
      Taken together, these studies suggest that SK and BK channels contribute to
      ethanol tolerance and adaptive plasticity.

PMID- 19389203
TI  - ADAMTS13: what it does, how it works, and why it's important.

PMID- 19389204
TI  - Additive solutions for platelets: is it time for North America to go with the
      flow?

PMID- 19389205
TI  - Diagnostic complexities in autoimmune hemolytic anemias.

PMID- 19389206
TI  - Transfusion Medicine Illustrated. The importance of visually inspecting cord
      blood units upon receipt.

PMID- 19389207
TI  - ADAMTS13 binds to CD36: a potential mechanism for platelet and endothelial
      localization of ADAMTS13.
AB  - BACKGROUND: ADAMTS13 cleaves ultralarge von Willebrand factor (VWF) and plays a
      significant role in vascular biology and thrombotic thrombocytopenic purpura.
      CD36, a transmembrane protein present on endothelial cells and platelets (PLTs),
      binds to thrombospondin via three thrombospondin type 1 repeats. ADAMTS13
      contains eight thrombospondin type 1 repeats. STUDY DESIGN AND METHODS: An enzyme
      linked immunoassay was used to explore the binding of recombinant human CD36
      (rHuCD36) to recombinant human ADAMTS13 (rHuADAMTS13). A competition assay
      between rHuADAMTS13 and recombinant human (rHu)-thrombospondin-2 for binding to
      CD36 was then performed. Subsequently, binding of rHuADAMTS13 to PLT membrane
      fragments expressing CD36 (PLT glycoprotein IV) and glycoprotein Ib/IX was
      assessed. To examine the functional significance of an ADAMTS13-CD36 interaction,
      ADAMTS13 activity measured by a fluorescence resonance energy transfer assay was
      investigated in the presence of either rHuCD36 or concentrated PLTs. RESULTS:
      rHuCD36 bound to rHuADAMTS13 in a dose-dependent fashion. rHu-thrombospondin-2
      competed with ADAMTS13 for CD36 occupancy, but even high concentrations of rHu
      thrombospondin-2 failed to completely block binding of rHuADAMTS13 to rHuCD36.
      rHuADAMTS13 bound to PLT membrane fragments expressing CD36 (PLT glycoprotein IV)
      in preference to PLT membrane fragments expressing glycoprotein Ib/IX. ADAMTS13
      activity was not inhibited by the presence of either rHuCD36 or concentrated
      PLTs. CONCLUSION: rHuADAMTS13 binds to both rHuCD36 and PLT membrane CD36 in
      vitro. The binding of CD36 to rHuADAMTS13 with retention of its enzymatic
      activity is consistent with a proposed role for CD36 in localizing ADAMTS13 on
      the endothelial cell surface where it regulates the cleavage of VWF.

PMID- 19389208
TI  - Factors affecting the frequency of red blood cell outdates: an approach to
      establish benchmarking targets.
AB  - BACKGROUND: Benchmarking is a useful tool to identify best practices and to
      compare an organization's performance with that of similar peers, allowing for
      continuous quality improvement. In this study, a provincial database of red blood
      cell (RBC) product inventory/disposition in hospitals was analyzed to identify
      factors that affected RBC outdates and to systematically establish optimal target
      levels for RBC outdates. STUDY DESIGN AND METHODS: RBC inventory/disposition data
      for a 21-month period from 156 hospitals were analyzed using logistic regression
      techniques to identify factors that affected RBC outdating (month of the year,
      distance from the blood supplier, monthly transfusion activity, hospital type,
      and provincial region). The results were used to categorize hospitals into
      groupings that accounted for the factors affecting wastage. Within each grouping,
      the lower quartile was selected as the optimal target threshold. RESULTS: Three
      factors were identified as significantly affecting RBC outdating: distance from
      the blood supplier, mean monthly transfusion activity, and month of the year.
      Accounting for these variables, three hospital groupings were identified and
      benchmarking targets were established for mean monthly RBC outdating: There were
      73 hospitals in Group 1 and their target level was 0.4 percent, 59 hospitals in
      Group 2 with a target of 1.1 percent, and 24 hospitals in Group 3 with a target
      of 20.3 percent. CONCLUSION: A method is described for establishing evidence
      based benchmarking targets for RBC outdating that allows for hospitals to be
      grouped with similar peers taking into account logistic factors that impact on
      product outdating.

PMID- 19389209
TI  - The effects of liberal versus restrictive transfusion thresholds on ambulation
      after hip fracture surgery.
AB  - BACKGROUND: Perioperative anemia leads to increased morbidity and mortality and
      potentially inhibits rehabilitation after hip fracture surgery. As such, the
      optimum transfusion threshold after hip fracture surgery is unknown. PATIENTS AND
      METHODS: A total of 120 elderly, cognitively intact hip fracture patients
      admitted from their own home were randomly assigned to receive transfusion at a
      hemoglobin threshold of 10.0 g per dL (liberal) versus 8.0 g per dL (restrictive)
      in the entire perioperative period. Patients were treated according to a well
      defined multimodal rehabilitation program. Primary outcome was postoperative
      functional mobility measured with the cumulated ambulation score (CAS). RESULTS:
      Patients in the liberal group received transfusions more frequently than those in
      the restrictive group (44 patients vs. 22 patients; p < 0.01) and received more
      transfusions during hospitalization (median, 2 units [interquartile range, 1-2]
      vs. 1 [1-2]; p < 0.0001). There were no significant differences in postoperative
      rehabilitation scores (CAS: median, 9 [9-15] vs. 9 [9-13.5]; p = 0.46) or in
      length of stay (median, 18 days vs. 16 days, respectively; p = 0.46). There were
      fewer patients in the liberal transfusion group with cardiovascular complications
      (2% vs. 10%; p = 0.05) and a lower mortality (0% vs. 8%; p = 0.02). CONCLUSION:
      Although a liberal transfusion trigger did not result in increased ambulation
      scores, restrictive transfusion thresholds should be treated with caution in
      elderly high-risk hip fracture patients, until their safety has been proved in
      larger randomized studies.

PMID- 19389210
TI  - Impact of a policy to permit the return of donors repeat-reactive to the Abbott
      PRISM antibody to hepatitis B core antigen assay.
AB  - BACKGROUND: The expected donor loss from recent implementation of antibody to
      hepatitis B core antigen (anti-HBc) testing in Canada was uncertain but
      potentially significant based on US experience. To reduce donor loss from false
      reactive tests, repeat-reactive donors without other evidence of infection were
      eligible to return. The aim was to evaluate the impact of anti-HBc testing on
      donor loss and to evaluate the effectiveness of this policy. STUDY DESIGN AND
      METHODS: For each donor in the first year of implementation (April 9, 2005-April
      8, 2006) repeat-reactive for the presence of anti-HBc only but eligible to return
      (screening test for hepatitis B surface antigen-negative, plus not reactive to
      antibody to hepatitis B surface antigen [anti-HBs] and hepatitis B virus [HBV]
      DNA supplemental tests), 10 matched donors not reactive to the anti-HBc assay
      were selected. Return rates over 2 years were compared using conditional logistic
      regression. Testing outcomes were tabulated. RESULTS: Over the first year of
      testing, 412,236 donors (951,423 donations) were tested for anti-HBc, and 4,489
      donors were repeat-reactive (1.3% of first-time donors, 1.0% of repeat donors).
      Of these 85.6 percent were also reactive for the presence of anti-HBs and/or HBV
      DNA supplemental tests leaving less than 15 percent eligible to return, of whom
      73 percent returned (vs. 90% of controls, p < 0.001). Of the 300 anti-HBc repeat
      reactive returning donors, 74 percent were anti-HBc repeat-reactive again (thus
      permanently deferred), 19 percent were deferred for other reasons versus 14
      percent of controls (p < 0.05), and 7 percent (21 donors) did not react and were
      eligible to continue donating. CONCLUSION: Most donors repeat-reactive for the
      presence of anti-HBc likely have past exposure to HBV. If eligible, most are
      willing to return, but likely to test anti-HBc repeat-reactive again.

PMID- 19389211
TI  - Associations between West Nile virus infection and symptoms reported by blood
      donors identified through nucleic acid test screening.
AB  - BACKGROUND: Blood collected in the United States and Canada is screened for West
      Nile virus (WNV) using nucleic acid testing (NAT). The role that donor-reported
      symptoms of infection disclosed at or shortly after donation may play in
      enhancing blood safety has been debated. Little data are available on subsequent
      manifestations of WNV-specific disease outcomes in viremic donors. STUDY DESIGN
      AND METHODS: Donors with initially reactive NAT results were informed by
      telephone and asked to complete symptom interviews. The questionnaires are
      focused on three time periods: the week before, the day of, and the 2 weeks after
      donation. Symptoms and risk factors were compared between confirmed-positive and
      false-positive donors (classified based on confirmatory NAT and serology).
      Additional analyses comparing confirmed-positive symptomatic and asymptomatic
      donors were conducted. RESULTS: A total of 423 of 536 initially reactive donors
      were interviewed between 2003 and 2006: 292 confirmed-positive for WNV and 131
      false-positive. Individual symptoms were not significant predictors of WNV
      infection, except skin rash in the week before donation (odds ratio [OR], 3.0;
      95% confidence interval [CI], 1.2-7.9) and body aches in the period after
      donation (OR, 2.8; 95% CI, 1.1-7.4). Specific combinations of symptoms were not
      good predictors of infection, but donors with three or more concurrent symptoms
      before donation were more likely to have WNV infection (OR, 2.5; 95% CI, 1.2
      5.1). Demographic characteristics, predonation symptoms, and serology profiles in
      confirmed-positive donors did not predict postdonation symptom severity. Thirty
      five confirmed-positive donors (12%) sought medical care for WNV infection, with
      two hospitalizations, but no cases of neuroinvasive disease. CONCLUSION: The
      number rather than type of symptoms is associated with confirmed WNV infection,
      but the overall predictive value is low. Very few infected donors develop
      clinically significant disease.

PMID- 19389212
TI  - Sensitivity of two hepatitis B virus, hepatitis C virus (HCV), and human
      immunodeficiency virus (HIV) nucleic acid test systems relative to hepatitis B
      surface antigen, anti-HCV, anti-HIV, and p24/anti-HIV combination assays in
      seroconversion panels.
AB  - BACKGROUND: Accurate determination of the infectious window period (IWP) that
      remains with individual-donation (ID) or minipool (MP) NAT compared to those with
      serology assays is essential for residual risk estimations. STUDY DESIGN AND
      METHODS: The relative sensitivity of the Procleix Tigris system (Gen
      Probe/Chiron) used in ID-NAT format and cobas s 201 (Roche Molecular Systems)
      applied in 1:6 diluted samples to mimic six-minipool (MP6) nucleic acid test
      (NAT) was assessed by quadruplicate testing of five seroconversion panels per
      marker. A mathematical analysis based on the log-linear increase of viremia in
      the ramp-up phase, as established with bDNA 3.0 assays enabled estimation of the
      IWP for human immunodeficiency virus (HIV) and hepatitis B virus (HBV) assays.
      RESULTS: The mean IWPs were Tigris HIV RNA 5.5 days, s 201 (1:6) HIV RNA 7.4
      days, GenScreen Plus p24/anti-HIV 17.8 days, PRISM anti-HIV 19.0 days, Tigris HBV
      DNA 20.6 days, s 201 (1:6) HBV DNA 22.6 days, Bio-Rad hepatitis B surface antigen
      (HBsAg) 37.8 days, and PRISM HBsAg 35.5 days. At estimated 50 percent NAT
      seroconversion rates, s 201 (1:6) and Tigris showed mean window-period reduction
      times (WPRTs) of 30.5 to 35.5 days to hepatitis C virus antibody (anti-HCV)
      assays, 10.4 to 13.5 days to anti-HIV, or combination p24/anti-HIV assays and
      12.8 to 17.2 days to HBsAg assays. CONCLUSIONS: Tigris ID-NAT detected HIV RNA 2
      days earlier than s 201 MP6-NAT, but the difference in sensitivity between the
      two NAT systems was not significant in HBV seroconversion panels. Insufficient
      seroconversion samples were available for reliable modeling of WPRT in early HCV
      infection, but 1.4 to 2.0 days could be predicted by translating analytical
      sensitivity data. Both multiplex NAT systems demonstrate significant WPRTs
      compared to (combined) antigen and antibody assays.

PMID- 19389213
TI  - Cost-effectiveness of additional hepatitis B virus nucleic acid testing of
      individual donations or minipools of six donations in the Netherlands.
AB  - BACKGROUND: To further reduce the risk of hepatitis B virus (HBV) transmission by
      blood transfusion, nucleic acid testing (NAT) can be employed. The aim of this
      study is to estimate the incremental cost-effectiveness ratio (ICER) in the
      Netherlands of employing a triplex NAT assay aimed at HBV nucleic acid detection
      in individual donations (ID-NAT) or in minipools of 6 donations (MP-6-NAT),
      compared to a triplex NAT assay in minipools of 24 donations (MP-24-NAT). STUDY
      DESIGN AND METHODS: A mathematical model was made of the whole transfusion chain
      from donors to recipients of blood in the Netherlands. The annual number of
      avoided HBV transmissions was estimated with the window-period incidence model.
      The natural history of a HBV infection in recipients is described by a Markov
      model. RESULTS: The ICER of adding HBV MP-6-NAT or HBV ID-NAT in the Netherlands
      is Euro303,218 (95% confidence interval [CI], Euro233,001-Euro408,388) and
      Euro518,995 (95% CI, Euro399,359-Euro699,120) per quality-adjusted life-year,
      respectively. The ICER strongly correlates with the age of transfusion
      recipients. CONCLUSION: The cost-effectiveness of additional HBV NAT is limited
      by the limited loss of life caused by HBV transmission. Despite a higher
      effectiveness, HBV ID-NAT is less cost-effective than MP-6-NAT due to higher
      costs. A future equivalent participation of immigrants from HBV-endemic countries
      in the donor base renders HBV NAT only slightly more cost-effective.

PMID- 19389214
TI  - Removal of Plasmodium falciparum-infected red blood cells from whole blood by
      leukoreduction filters.
AB  - BACKGROUND: There has been an unexplained decrease in the incidence of
      transfusion-transmitted malaria in recent years. The decrease in incidence has
      paralleled the increasing use of leukoreduction filters. Malaria-infected red
      blood cells (RBCs) share surface characteristics of hemoglobin S-containing
      cells. Because units collected from donors with sickle trait do not filter
      optimally due to adherence of RBCs to the filters, the possibility that malaria
      infected RBCs may also adhere to filters was investigated. STUDY DESIGN AND
      METHODS: Malaria-infected whole blood or calcium ionophore (A25187)-treated and
      control RBCs were filtered with leukoreduction filters. Quantitation of malaria
      infected RBCs before and after filtration was performed by flow cytometry to
      determine the presence of DNA within RBCs, indicating malaria infection. Annexin
      V binding was also determined before and after filtration of RBCs treated with
      A25187. Immediately after filtration, filters were fixed and examined by scanning
      and transmission electron microscopy. RESULTS: There were at least three
      configurations of adherence of malaria-infected RBCs demonstrated within the
      filters. The first was direct adherence of infected RBCs to filter fibers; the
      second involved adherence of malaria-infected RBCs to platelets, which were
      adherent to filter fibers; and the third was adherence of infected RBCs to other
      RBCs. Filtration also resulted in preferential removal of phosphatidylserine (PS)
      expressing cells as seen by the reduction of annexin V binding after filtration.
      This was further confirmed by electron micrographic examination of the filters in
      which untreated RBCs sit within the filter resting on top of filter fibers;
      however, calcium ionophore-treated RBCs are seen to cling tightly to the fibers.
      CONCLUSIONS: PS expression by RBCs leads to their adherence within leukoreduction
      filters. Malaria-infected RBCs are retained via more than one mechanism. The
      efficiency of removal requires further study.

PMID- 19389215
TI  - Clinical-grade purification of natural killer cells in haploidentical
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: Because of a high risk of graft-versus-host disease (GVHD), donor
      lymphocyte infusions with unmodified lymphapheresis products are not used after
      haploidentical hematopoietic stem cell transplantation. Natural killer (NK) cells
      have antitumor activity and may consolidate engraftment without inducing GVHD.
      Production of NK cells under good manufacturing practice (GMP) conditions in a
      sufficient number is difficult. STUDY DESIGN AND METHODS: Twenty-four apheresis
      procedures and subsequent NK-cell enrichment from 14 haploidentical donors were
      performed. NK-cell enrichment was performed using a GMP suitable immunomagnetic
      procedure. Factors influencing the NK-cell recovery, purity, and NK-cell dose
      were analyzed. RESULTS: A median number of 4.9 x 10(8) NK cells were obtained and
      median NK-cell recovery was 58 percent. Median T-cell depletion was 4.32 log. The
      absolute NK-cell number in the final product after processing significantly
      correlated with the preharvest NK-cell content of the peripheral blood (p =
      0.002, r = 0.867). The NK-cell recovery was inversely correlated to the absolute
      NK-cell number in the apheresis product (p = 0.01, r = -0.51). The NK-cell dose
      per kg of body weight of the patient was inversely correlated to the weight of
      the patient (p = 0.007, r = -0.533). CONCLUSION: Donors with a high NK-cell count
      in peripheral blood are likely to provide NK-cell products with the highest cell
      number. However, maximal NK-cell dose is limited and high NK-cell doses may only
      be obtained for patients with a low body weight, making children and young adults
      the best candidates for NK-cell therapy.

PMID- 19389216
TI  - The Rapa Nui caveat.

PMID- 19389217
TI  - Presence of meconium-stained amniotic fluid in cesarean deliveries increases the
      total nucleated cell content of umbilical cord blood units.

PMID- 19389219
TI  - Establishment of a novel method for detecting Nak antibodies by using a panel
      cell line.

PMID- 19389220
TI  - Complications of plasma exchange in patients treated for thrombotic
      thrombocytopenic purpura. IV. An additional study of 43 consecutive patients,
      2005 to 2008.

PMID- 19389221
TI  - In vitro activity of pyronaridine against Plasmodium falciparum and comparative
      evaluation of anti-malarial drug susceptibility assays.
AB  - BACKGROUND: Pyronaridine, a Mannich base anti-malarial with high efficacy against
      drug resistant Plasmodium falciparum, is currently evaluated as a fixed dose
      combination with artesunate for the treatment of uncomplicated malaria. In this
      study, the in vitro activity of pyronaridine against clinical isolates of P.
      falciparum from Lambarene, Gabon, was assessed in order to obtain baseline data
      on its activity prior to its future use in routine therapy. Moreover, follow-up
      assessment on the in vitro activity of chloroquine, artesunate and quinine was
      performed. METHODS: In vitro response of field isolates of P. falciparum to
      pyronaridine, chloroquine, artesunate and quinine was assessed using the
      traditional WHO microtest. In addition, the histidine-rich protein 2 (HRP-2)
      assay was performed and evaluated for its future implementation for follow-up of
      drug susceptibility testing. RESULTS: Pyronaridine exhibited a high in vitro
      activity against P. falciparum, with a geometric mean cut-off concentration of
      9.3 nmol/l. Fifty percent effective concentrations were 1.9 nmol/l and 2.0 nmol/l
      in the WHO microtest and HRP-2 assay, respectively. Results matched closely in
      vivo findings from a recent clinical trial on pyronaridine-artesunate treatment.
      One isolate showed diminished sensitivity to artesunate. For chloroquine and
      quinine resistance levels were comparable to prior studies from Lambarene.
      Results from the novel HRP-2 assay corresponded well to those obtained by the WHO
      microtest. CONCLUSION: Pyronaridine is highly active in chloroquine-resistant
      parasites and seems a promising partner drug for artemisinin-based combination
      therapy in Africa.

PMID- 19389223
TI  - Relief-oriented use of marijuana by teens.
AB  - BACKGROUND: There are indications that marijuana is increasingly used to
      alleviate symptoms and for the treatment of a variety of medical conditions both
      physical and psychological. The purpose of this study was to describe the health
      concerns and problems that prompt some adolescents to use marijuana for
      therapeutic reasons, and their beliefs about the risks and benefits of the
      therapeutic use of marijuana. METHODS: As part of a larger ethnographic study of
      63 adolescents who were regular marijuana users, we analyzed interviews conducted
      with 20 youth who self-identified as using marijuana to relieve or manage health
      problems. RESULTS: Thematic analysis revealed that these teens differentiated
      themselves from recreational users and positioned their use of marijuana for
      relief by emphasizing their inability to find other ways to deal with their
      health problems, the sophisticated ways in which they titrated their intake, and
      the benefits that they experienced. These teens used marijuana to gain relief
      from difficult feelings (including depression, anxiety and stress), sleep
      difficulties, problems with concentration and physical pain. Most were not overly
      concerned about the risks associated with using marijuana, maintaining that their
      use of marijuana was not 'in excess' and that their use fit into the realm of
      'normal.' CONCLUSION: Marijuana is perceived by some teens to be the only
      available alternative for teens experiencing difficult health problems when
      medical treatments have failed or when they lack access to appropriate health
      care.

PMID- 19389222
TI  - Early markers of airways inflammation and occupational asthma: rationale, study
      design and follow-up rates among bakery, pastry and hairdressing apprentices.
AB  - BACKGROUND: Occupational asthma is a common type of asthma caused by a specific
      agent in the workplace. The basic alteration of occupational asthma is airways
      inflammation. Although most patients with occupational asthma are mature adults,
      there is evidence that airways inflammation starts soon after inception of
      exposure, including during apprenticeship. Airways hyper responsiveness to
      methacholine is a valid surrogate marker of airways inflammation, which has
      proved useful in occupational epidemiology. But it is time-consuming, requires
      active subject's cooperation and is not readily feasible. Other non-invasive and
      potentially more useful tests include the forced oscillation technique,
      measurement of fraction exhaled nitric oxide, and eosinophils count in nasal
      lavage fluid. METHODS AND DESIGN: This study aims to investigate early
      development of airways inflammation and asthma-like symptoms in apprentice
      bakers, pastry-makers and hairdressers, three populations at risk of occupational
      asthma whose work-related exposures involve agents of different nature. The
      objectives are to (i) examine the performance of the non-invasive tests cited
      above in detecting early airways inflammation that might eventually develop into
      occupational asthma; and (ii) evaluate whether, and how, constitutional (e.g.
      atopy) and behavioural (e.g. smoking) risk factors for occupational asthma
      modulate the effects of allergenic and/or irritative substances involved in these
      occupations. This paper presents the study rationale and detailed protocol.
      DISCUSSION: Among 441 volunteers included at the first visit, 354 attended the
      fourth one. Drop outs were investigated and showed unrelated to the study
      outcome. Sample size and follow-up participation rates suggest that the data
      collected in this study will allow it to meet its objectives.

PMID- 19389224
TI  - Use of the lambda Red-recombineering method for genetic engineering of Pantoea
      ananatis.
AB  - BACKGROUND: Pantoea ananatis, a member of the Enterobacteriacea family, is a new
      and promising subject for biotechnological research. Over recent years,
      impressive progress in its application to L-glutamate production has been
      achieved. Nevertheless, genetic and biotechnological studies of Pantoea ananatis
      have been impeded because of the absence of genetic tools for rapid construction
      of direct mutations in this bacterium. The lambda Red-recombineering technique
      previously developed in E. coli and used for gene inactivation in several other
      bacteria is a high-performance tool for rapid construction of precise genome
      modifications. RESULTS: In this study, the expression of lambda Red genes in P.
      ananatis was found to be highly toxic. A screening was performed to select
      mutants of P. ananatis that were resistant to the toxic affects of lambda Red. A
      mutant strain, SC17(0) was identified that grew well under conditions of
      simultaneous expression of lambda gam, bet, and exo genes. Using this strain,
      procedures for fast introduction of multiple rearrangements to the Pantoea
      ananatis genome based on the lambda Red-dependent integration of the PCR
      generated DNA fragments with as short as 40 bp flanking homologies have been
      demonstrated. CONCLUSION: The lambda Red-recombineering technology was
      successfully used for rapid generation of chromosomal modifications in the
      specially selected P. ananatis recipient strain. The procedure of electro
      transformation with chromosomal DNA has been developed for transfer of the marked
      mutation between different P. ananatis strains. Combination of these techniques
      with lambda Int/Xis-dependent excision of selective markers significantly
      accelerates basic research and construction of producing strains.

PMID- 19389225
TI  - Antidepressants inhibit P2X4 receptor function: a possible involvement in
      neuropathic pain relief.
AB  - BACKGROUND: Neuropathic pain is characterized by pain hypersensitivity to
      innocuous stimuli (tactile allodynia) that is nearly always resistant to known
      treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has
      been reported that some antidepressants are effective for treating neuropathic
      pain. However, the underlying molecular mechanisms are not well understood. We
      have recently demonstrated that blocking P2X4 receptors in the spinal cord
      reverses tactile allodynia after peripheral nerve injury in rats, implying that
      P2X4 receptors are a key molecule in neuropathic pain. We investigated a possible
      role of antidepressants as inhibitors of P2X4 receptors and analysed their
      analgesic mechanism using an animal model of neuropathic pain. RESULTS:
      Antidepressants strongly inhibited ATP-mediated Ca2+ responses in P2X4 receptor
      expressing 1321N1 cells, which are known to have no endogenous ATP receptors.
      Paroxetine exhibited the most powerful inhibition of calcium influx via rat and
      human P2X4 receptors, with IC50 values of 2.45 microM and 1.87 microM,
      respectively. Intrathecal administration of paroxetine produced a striking
      antiallodynic effect in an animal model of neuropathic pain. Co-administration of
      WAY100635, ketanserin or ondansetron with paroxetine induced no significant
      change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic
      effect of paroxetine was observed even in rats that had received intrathecal
      pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5
      hydroxytryptamine. CONCLUSION: These results suggest that paroxetine acts as a
      potent analgesic in the spinal cord via a mechanism independent of its inhibitory
      effect on serotonin transporters. Powerful inhibition on P2X4 receptors may
      underlie the analgesic effect of paroxetine, and it is possible that some
      antidepressants clinically used in patients with neuropathic pain show
      antiallodynic effects, at least in part via their inhibitory effects on P2X4
      receptors.

PMID- 19389226
TI  - Timing of organogenesis support basal position of turtles in the amniote tree of
      life.
AB  - BACKGROUND: The phylogenetic position of turtles is the most disputed aspect in
      the reconstruction of the land vertebrate tree of life. This controversy has
      arisen after many different kinds and revisions of investigations of molecular
      and morphological data. Three main hypotheses of living sister-groups of turtles
      have resulted from them: all reptiles, crocodiles + birds or squamates + tuatara.
      Although embryology has played a major role in morphological studies of
      vertebrate phylogeny, data on developmental timing have never been examined to
      explore and test the alternative phylogenetic hypotheses. We conducted a
      comprehensive study of published and new embryological data comprising 15 turtle
      and eight tetrapod species belonging to other taxa, integrating for the first
      time data on the side-necked turtle clade. RESULTS: The timing of events in
      organogenesis of diverse character complexes in all body regions is not uniform
      across amniotes and can be analysed using a parsimony-based method. Changes in
      the relative timing of particular events diagnose many clades of amniotes and
      include a phylogenetic signal. A basal position of turtles to the living saurian
      clades is clearly supported by timing of organogenesis data. CONCLUSION: The
      clear signal of a basal position of turtles provided by heterochronic data
      implies significant convergence in either molecular, adult morphological or
      developmental timing characters, as only one of the alternative solutions to the
      phylogenetic conundrum can be right. The development of a standard reference
      series of embryological events in amniotes as presented here should enable future
      improvements and expansion of sampling and thus the examination of other
      hypotheses about phylogeny and patterns of the evolution of land vertebrate
      development.

PMID- 19389227
TI  - Acetylation of PAMAM dendrimers for cellular delivery of siRNA.
AB  - BACKGROUND: The advancement of gene silencing via RNA interference is limited by
      the lack of effective short interfering RNA (siRNA) delivery vectors. Rational
      design of polymeric carriers has been complicated by the fact that most chemical
      modifications affect multiple aspects of the delivery process. In this work, the
      extent of primary amine acetylation of generation 5 poly(amidoamine) (PAMAM)
      dendrimers was studied as a modification for the delivery of siRNA to U87
      malignant glioma cells. RESULTS: PAMAM dendrimers were reacted with acetic
      anhydride to obtain controlled extents of primary amine acetylation. Acetylated
      dendrimers were complexed with siRNA, and physical properties of the complexes
      were studied. Dendrimers with up to 60% of primary amines acetylated formed
      approximately 200 nm complexes with siRNA. Increasing amine acetylation resulted
      in reduced polymer cytotoxicity to U87 cells, as well as enhanced dissociation of
      dendrimer/siRNA complexes. Acetylation of dendrimers reduced the cellular
      delivery of siRNA which correlated with a reduction in the buffering capacity of
      dendrimers upon amine acetylation. Confocal microscopy confirmed that escape from
      endosomes is a major barrier to siRNA delivery in this system. CONCLUSION:
      Primary amine acetylation of PAMAM dendrimers reduced their cytotoxicity to U87
      cells, and promoted the release of siRNA from dendrimer/siRNA complexes. A modest
      fraction (approximately 20%) of primary amines of PAMAM can be modified while
      maintaining the siRNA delivery efficiency of unmodified PAMAM, but higher degrees
      of amine neutralization reduced the gene silencing efficiency of PAMAM/siRNA
      delivery vectors.

PMID- 19389228
TI  - Linkages between animal and human health sentinel data.
AB  - INTRODUCTION: In order to identify priorities for building integrated
      surveillance systems that effectively model and predict human risk of zoonotic
      diseases, there is a need for improved understanding of the practical options for
      linking surveillance data of animals and humans. We conducted an analysis of the
      literature and characterized the linkage between animal and human health data. We
      discuss the findings in relation to zoonotic surveillance and the linkage of
      human and animal data. METHODS: The Canary Database, an online bibliographic
      database of animal-sentinel studies was searched and articles were classified
      according to four linkage categories. RESULTS: 465 studies were identified and
      assigned to linkage categories involving: descriptive, analytic, molecular, or no
      human outcomes of human and animal health. Descriptive linkage was the most
      common, whereby both animal and human health outcomes were presented, but without
      quantitative linkage between the two. Rarely, analytic linkage was utilized in
      which animal data was used to quantitatively predict human risk. The other two
      categories included molecular linkage, and no human outcomes, which present
      health outcomes in animals but not humans. DISCUSSION: We found limited use of
      animal data to quantitatively predict human risk and listed the methods from the
      literature that performed analytic linkage. The lack of analytic linkage in the
      literature might not be solely related to technological barriers including access
      to electronic database, statistical software packages, and Geographical
      Information System (GIS). Rather, the problem might be from a lack of
      understanding by researchers of the importance of animal data as a 'sentinel' for
      human health. Researchers performing zoonotic surveillance should be aware of the
      value of animal-sentinel approaches for predicting human risk and consider
      analytic methods for linking animal and human data. Qualitative work needs to be
      done in order to examine researchers' decisions in linkage strategies between
      animal and human data.

PMID- 19389229
TI  - Development and evaluation of a tool for the assessment of footwear
      characteristics.
AB  - BACKGROUND: Footwear characteristics have been linked to falls in older adults
      and children, and the development of many musculoskeletal conditions. Due to the
      relationship between footwear and pathology, health professionals have a
      responsibility to consider footwear characteristics in the etiology and treatment
      of various patient presentations. In order for health professionals and
      researchers to accurately and efficiently critique an individual's footwear, a
      valid and reliable footwear assessment tool is required. The aim of this study
      was to develop a simple, efficient, and reliable footwear assessment tool
      potentially suitable for use in a range of patient populations. METHODS:
      Consideration of previously published tools, other footwear related literature,
      and clinical considerations of three therapists were used to assist in the
      development of the tool. The tool was developed to cover fit, general features,
      general structure, motion control properties, cushioning, and wear patterns. A
      total of 15 participants (who provided two pairs of shoes each) were recruited,
      and assessment using the scale was completed on two separate occasions (separated
      by 1 - 3 weeks) by a physiotherapist and a podiatrist on each participant's
      dominant foot. Intra-rater and inter-rater reliability were evaluated using intra
      class correlation coefficients (ICCs) (model 2, 1) and the 95% limits of
      agreement (95% LOAs) for continuous items, and percentage agreement and kappa
      (kappa) statistics for categorical items. RESULTS: All categorical items
      demonstrated high percentage agreement statistic for intra-rater (83 - 100%) and
      inter-rater (83 - 100%) comparisons. With the exception of last shape and
      objective measures used to categorise the adequacy of length, excellent intra
      rater (ICC = 0.91 - 1.00) and inter-rater reliability (ICC = 0.90 - 1.00) was
      indicated for continuous items in the tool, including the motion control
      properties scale (0.91 - 0.95). CONCLUSION: A comprehensive footwear assessment
      tool with good face validity has been developed to assist future research and
      clinical footwear assessment. Generally good reliability amongst all items
      indicates that the tool can be used with confidence in research and clinical
      settings. Further research is now required to determine the clinical validity of
      each item in various patient populations.

PMID- 19389230
TI  - Disease activity level, remission and response in established rheumatoid
      arthritis: performance of various criteria sets in an observational cohort,
      treated with anti-TNF agents.
AB  - BACKGROUND: Most composite indices of disease activity and response criteria in
      RA have been validated and compared in clinical trials rather than routine care.
      We therefore wanted to compare the performance of the DAS28, SDAI and CDAI
      activity indices, their activity states, their response criteria, and also
      compare with the ACR response criteria in an observational clinical setting.
      METHODS: Agreement between the criteria sets was investigated using kappa
      statistics in a non-randomized cohort of 1789 RA patients from southern Sweden,
      starting their first course of anti-TNF-treatment. Mean disease duration was 12
      years. Completer analysis was used. RESULTS: Agreement between high, moderate and
      low activity states was moderate or substantial, with kappa = 0.5 or better for
      all criteria. Agreement between SDAI and CDAI disease states was > 90% in these
      categories with kappa > 0.8. DAS28 original and modified cut point remission had
      good agreement (kappa = 0.91). Agreement between responses was substantial at the
      overall/ACR20 level (about 95%, kappa = 0.7 or better) for all criteria. By
      contrast, agreement was poor between moderate and high level responses.
      CONCLUSION: Disease activity states according to the various indices perform
      similarly and show substantial agreement at all levels except remission.
      Agreement between SDAI and CDAI states is excellent. Response criteria, applied
      at the individual patient level, are hard to interpret and show poor agreement,
      except at the lowest level of response. Thus, they should not be applied
      uncritically in clinical practice.

PMID- 19389231
TI  - Chronic whiplash and central sensitization; an evaluation of the role of a
      myofascial trigger points in pain modulation.
AB  - OBJECTIVE: It has been established that chronic neck pain following whiplash is
      associated with the phenomenon of central sensitization, in which injured and
      uninjured parts of the body exhibit lowered pain thresholds due to an alteration
      in central pain processing. it has furthermore been hypothesized that peripheral
      sources of nociception in the muscles may perpetuate central sensitization in
      chronic whiplash. the hypothesis explored in the present study was whether
      myofascial trigger points serve as a modulator of central sensitization in
      subjects with chronic neck pain. DESIGN: Controlled case series. SETTING:
      Outpatient chronic pain clinic. SUBJECTS: Seventeen patients with chronic and
      intractable neck pain and 10 healthy controls without complaints of neck pain.
      INTERVENTION: Symptomatic subjects received anesthetic infiltration of myofascial
      trigger points in the upper trapezius muscles and controls received the
      anesthetic in the thigh. OUTCOME MEASURES: pre and post injection cervical range
      of motion, pressure pain thresholds (ppt) over the infraspinatus, wrist extensor,
      and tibialis anterior muscles. sensitivity to light (photophobia) and subjects'
      perception of pain using a visual analog scale (vas) were also evaluated before
      and after injections. only the ppt was evaluated in the asymptomatic controls.
      RESULTS: Immediate (within 1 minute) alterations in cervical range of motion and
      pressure pain thresholds were observed following an average of 3.8 injections
      with 1-2 cc of 1% lidocaine into carefully identified trigger points. cervical
      range of motion increased by an average of 49% (p = 0.000) in flexion and 44% (p
      = 0.001) in extension, 47% (p = 0.000) and 28% (p < 0.016) in right and left
      lateral flexion, and a 27% (p = 0.002) and 45% (p = 0.000) in right and left
      rotation. ppt were found increased by 68% over the infraspinatus (p = 0.000), by
      78% over the wrist extensors (p = 0.000), and by 64% over the tibialis anterior
      (p = 0.002). Among 11 subjects with photophobia, only 2 remained sensitive to
      light after the trigger point injections (p = 0.033). Average vas dropped by 57%,
      from 6.1 to 2.6 (p = 0.000). No significant changes in ppt were observed in the
      control group following lidocaine infiltration of the thigh. CONCLUSION: The
      present data suggest that myofascial trigger points serve to perpetuate lowered
      pain thresholds in uninjured tissues. Additionally, it appears that lowered pain
      thresholds associated with central sensitization can be immediately reversed,
      even when associated with long standing chronic neck pain. Although the effects
      resulting from anesthesia of trigger points in the present study were temporary,
      it is possible that surgical excision or ablation of the same trigger points may
      offer more permanent solutions for chronic neck pain patients. Further study is
      needed to evaluate these and other options for such patients.

PMID- 19389233
TI  - Socio-spatial inequalities and the distribution of cash benefits to asthmatic
      children in Norway.
AB  - BACKGROUND: Previous research has observed large inequalities in the distribution
      of welfare benefits. The Norwegian welfare state includes several schemes that
      give households with children the opportunity to apply for public income support
      to compensate for expenses related to chronic disease. The aims of this study
      were to examine the geographic distribution of children receiving compensatory
      cash benefits because of a chronic asthma condition and to determine whether
      social or geographic factors account for area variations in uptake independent of
      the associations with need. RESULTS: Considerable variation between counties was
      evident, with rates of benefit uptake ranging from 10.5 recipients per 1,000
      children younger than nine years in the highest-ranking county, to 1.5 per 1,000
      in the lowest. It is argued that the observed area-level inequalities reflect
      more than variations in morbidity. In particular, the chance of receiving
      benefits reflects variations in the ability of street-level bureaucrats to inform
      families about their rights. Spatial variations also reflect, in part, the fact
      that families with different socio-economic standing inhabit different locations
      and that the threshold for receiving benefits is systematically lower for
      families with an academic background. CONCLUSION: To be able to refine the
      implementation of a welfare policy, a better understanding of the processes that
      generate the outcomes of the various welfare schemes and services is required.
      This can be achieved by adopting an approach to the study of outcomes of welfare
      policy that integrates both the social and geographic perspective, and that
      focuses on specific diagnoses or distributional procedures.

PMID- 19389232
TI  - Effects and mechanisms of action of sildenafil citrate in human chorionic
      arteries.
AB  - OBJECTIVES: Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is
      increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also
      emerging as a potential candidate for the treatment of intra-uterine growth
      retardation and for premature labor. Its effects in the feto-placental
      circulation are not known. Our objectives were to determine whether
      phosphodiesterase-5 is present in the human feto-placental circulation, and to
      characterize the effects and mechanisms of action of sildenafil citrate in this
      circulation. STUDY DESIGN: Ex vivo human chorionic plate arterial rings were used
      in all experiments. The presence of phosphodiesterase-5 in the feto-placental
      circulation was determined by western blotting and immunohistochemical staining.
      In a subsequent series of pharmacologic studies, the effects of sildenafil
      citrate in pre-constricted chorionic plate arterial rings were determined.
      Additional studies examined the role of cGMP and nitric oxide in mediating the
      effects of sildenafil. RESULTS: Phosphodiesterase-5 mRNA and protein was
      demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated
      phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced
      dose dependent vasodilatation at concentrations at and greater than 10 nM. Both
      the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase
      inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by
      sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the
      vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly
      enhanced the vasodilation produced by the NO donor sodium nitroprusside.
      CONCLUSION: Phosphodiesterase-5 is present in the feto-placental circulation.
      Sildenafil citrate vasodilates the feto-placental circulation via a cGMP
      dependent mechanism involving increased responsiveness to NO.

PMID- 19389234
TI  - Genetic variants of the promoter of the heme oxygenase-1 gene and their influence
      on cardiovascular disease (the Ludwigshafen Risk and Cardiovascular Health
      study).
AB  - BACKGROUND: Heme oxygenase-1 is an inducible cytoprotective enzyme which handles
      oxidative stress by generating anti-oxidant bilirubin and vasodilating carbon
      monoxide. A (GT)n dinucleotide repeat and a -413A>T single nucleotide
      polymorphism have been reported in the promoter region of HMOX1 to both influence
      the occurrence of coronary artery disease and myocardial infarction. We sought to
      validate these observations in persons scheduled for coronary angiography.
      METHODS: We included 3219 subjects in the current analysis, 2526 with CAD
      including a subgroup of CAD and MI (n = 1339) and 693 controls. Coronary status
      was determined by coronary angiography. Risk factors and biochemical parameters
      (bilirubin, iron, LDL-C, HDL-C, and triglycerides) were determined by standard
      procedures. The dinucleotide repeat was analysed by PCR and subsequent sizing by
      capillary electrophoresis, the -413A>T polymorphism by PCR and RFLP. RESULTS: In
      the LURIC study the allele frequency for the -413A>T polymorphism is A = 0,589
      and T = 0,411. The (GT)n repeats spread between 14 and 39 repeats with 22 (19.9%)
      and 29 (47.1%) as the two most common alleles. We found neither an association of
      the genotypes or allelic frequencies with any of the biochemical parameters nor
      with CAD or previous MI. CONCLUSION: Although an association of these
      polymorphisms with the appearance of CAD and MI have been published before, our
      results strongly argue against a relevant role of the (GT)n repeat or the -413A>T
      SNP in the HMOX1 promoter in CAD or MI.

PMID- 19389235
TI  - Alterations in vitamin D status and anti-microbial peptide levels in patients in
      the intensive care unit with sepsis.
AB  - BACKGROUND: Vitamin D insufficiency is common in hospitalized patients. Recent
      evidence suggests that vitamin D may enhance the innate immune response by
      induction of cathelicidin (LL-37), an endogenous antimicrobial peptide produced
      by macrophages and neutrophils. Thus, the relationship between vitamin D status
      and LL-37 production may be of importance for host immunity, but little data is
      available on this subject, especially in the setting of human sepsis syndrome and
      other critical illness. METHODS: Plasma concentrations of 25-hydroxyvitamin D
      (25(OH)D), vitamin D binding protein (DBP) and LL-37 in critically ill adult
      subjects admitted to intensive care units (ICUs) with sepsis and without sepsis
      were compared to healthy controls. RESULTS: Critically ill subjects had
      significantly lower plasma 25(OH)D concentrations compared to healthy controls.
      Mean plasma LL-37 levels were significantly lower in critically ill subjects
      compared to healthy controls. Vitamin D binding protein levels in plasma were
      significantly lower in critically ill subjects with sepsis compared to critically
      ill subjects without sepsis. There was a significant positive association between
      circulating 25(OH)D and LL-37 levels. CONCLUSION: This study demonstrates an
      association between critical illness and lower 25(OH)D and DBP levels in
      critically ill patients as compared to healthy controls. It also establishes a
      positive association between vitamin D status and plasma LL-37, which suggests
      that systemic LL-37 levels may be regulated by vitamin D status. Optimal vitamin
      D status may be important for innate immunity especially in the setting of
      sepsis. Further invention studies to examine this association are warranted.

PMID- 19389236
TI  - Mitochondrial phylogeography of baboons (Papio spp.): indication for
      introgressive hybridization?
AB  - BACKGROUND: Baboons of the genus Papio are distributed over wide ranges of Africa
      and even colonized parts of the Arabian Peninsula. Traditionally, five
      phenotypically distinct species are recognized, but recent molecular studies were
      not able to resolve their phylogenetic relationships. Moreover, these studies
      revealed para- and polyphyletic (hereafter paraphyletic) mitochondrial clades for
      baboons from eastern Africa, and it was hypothesized that introgressive
      hybridization might have contributed substantially to their evolutionary history.
      To further elucidate the phylogenetic relationships among baboons, we extended
      earlier studies by analysing the complete mitochondrial cytochrome b gene and the
      'Brown region' from 67 specimens collected at 53 sites, which represent all
      species and which cover most of the baboons' range. RESULTS: Based on
      phylogenetic tree reconstructions seven well supported major haplogroups were
      detected, which reflect geographic populations and discordance between
      mitochondrial phylogeny and baboon morphology. Our divergence age estimates
      indicate an initial separation into southern and northern baboon clades 2.09
      (1.54-2.71) million years ago (mya). We found deep divergences between
      haplogroups within several species (~2 mya, northern and southern yellow baboons,
      western and eastern olive baboons and northern and southern chacma baboons), but
      also recent divergence ages among species (< 0.7 mya, yellow, olive and hamadryas
      baboons in eastern Africa). CONCLUSION: Our study confirms earlier findings for
      eastern Africa, but shows that baboon species from other parts of the continent
      are also mitochondrially paraphyletic. The phylogenetic patterns suggest a
      complex evolutionary history with multiple phases of isolation and reconnection
      of populations. Most likely all these biogeographic events were triggered by
      multiple cycles of expansion and retreat of savannah biomes during Pleistocene
      glacial and inter-glacial periods. During contact phases of populations
      reticulate events (i.e. introgressive hybridization) were highly likely, similar
      to ongoing hybridization, which is observed between East African baboon
      populations. Defining the extent of the introgressive hybridization will require
      further molecular studies that incorporate additional sampling sites and nuclear
      loci.

PMID- 19389238
TI  - A portable system for collecting anatomical joint angles during stair ascent: a
      comparison with an optical tracking device.
AB  - BACKGROUND: Assessments of stair climbing in real-life situations using an
      optical tracking system are lacking, as it is difficult to adapt the system for
      use in and around full flights of stairs. Alternatively, a portable system that
      consists of inertial measurement units (IMUs) can be used to collect anatomical
      joint angles during stair ascent. The purpose of this study was to compare the
      anatomical joint angles obtained by IMUs to those calculated from position data
      of an optical tracking device. METHODS: Anatomical joint angles of the thigh,
      knee and ankle, obtained using IMUs and an optical tracking device, were compared
      for fourteen healthy subjects. Joint kinematics obtained with the two measurement
      devices were evaluated by calculating the root mean square error (RMSE) and by
      calculating a two-tailed Pearson product-moment correlation coefficient (r)
      between the two signals. RESULTS: Strong mean correlations (range 0.93 to 0.99)
      were found for the angles between the two measurement devices, as well as an
      average root mean square error (RMSE) of 4 degrees over all the joint angles,
      showing that the IMUs are a satisfactory system for measuring anatomical joint
      angles. CONCLUSION: These highly portable body-worn inertial sensors can be used
      by clinicians and researchers alike, to accurately collect data during stair
      climbing in complex real-life situations.

PMID- 19389237
TI  - Gene expression profiling in the synovium identifies a predictive signature of
      absence of response to adalimumab therapy in rheumatoid arthritis.
AB  - INTRODUCTION: To identify markers and mechanisms of resistance to adalimumab
      therapy, we studied global gene expression profiles in synovial tissue specimens
      obtained from severe rheumatoid arthritis (RA) patients before and after
      initiation of treatment. METHODS: Paired synovial biopsies were obtained from the
      affected knee of 25 DMARD (disease-modifying antirheumatic drug)-resistant RA
      patients at baseline (T0) and 12 weeks (T12) after initiation of adalimumab
      therapy. DAS28-CRP (disease activity score using 28 joint counts-C-reactive
      protein) scores were computed at the same time points, and patients were
      categorized as good, moderate, or poor responders according to European League
      Against Rheumatism criteria. Global gene expression profiles were performed in a
      subset of patients by means of GeneChip Human Genome U133 Plus 2.0 Arrays, and
      confirmatory immunohistochemistry experiments were performed on the entire
      cohort. RESULTS: Gene expression studies performed at baseline identified 439
      genes associated with poor response to therapy. The majority (n = 411) of these
      genes were upregulated in poor responders and clustered into two specific
      pathways: cell division and regulation of immune responses (in particular,
      cytokines, chemokines, and their receptors). Immunohistochemistry experiments
      confirmed that high baseline synovial expression of interleukin-7 receptor alpha
      chain (IL-7R), chemokine (C-X-C motif) ligand 11 (CXCL11), IL-18, IL-18 receptor
      accessory (IL-18rap), and MKI67 is associated with poor response to adalimumab
      therapy. In vitro experiments indicated that genes overexpressed in poor
      responders could be induced in fibroblast-like synoviocytes (FLS) cultures by the
      addition of tumor necrosis factor-alpha (TNF-alpha) alone, IL-1beta alone, the
      combination of TNF-alpha and IL-17, and the combination of TNF-alpha and IL
      1beta. CONCLUSIONS: Gene expression studies of the RA synovium may be useful in
      the identification of early markers of response to TNF blockade. Genes
      significantly overexpressed at baseline in poor responders are induced by several
      cytokines in FLSs, thereby suggesting a role for these cytokines in the
      resistance to TNF blockade in RA.

PMID- 19389239
TI  - The accuracy of clinical malaria case reporting at primary health care facilities
      in Honiara, Solomon Islands.
AB  - BACKGROUND: The accuracy of malaria case reporting is challenging due to
      restricted human and material resources in many countries. The reporting often
      depends on the clinical diagnosis because of the scarcity of microscopic
      examinations. Particularly, clinical malaria case reporting by primary health
      care facilities (local clinics), which constitutes the baseline data of
      surveillance, has never previously been sufficiently evaluated. In order to
      improve the malaria reporting system to the level required to eventually
      eliminate this disease, this study estimates the gaps between the records of
      clinics and government statistics regarding the incidence of clinical malaria,
      and then also examines some factors that might explain the data discrepancy,
      including such variables as clinic staffing and record keeping. METHODS: All
      medical records for outpatients in 2007, handwritten by nurses, were collected
      from local clinics in Honiara, the capital of the Solomon Islands. The all
      monthly clinical malaria cases were then recalculated. The corresponding monthly
      data in official statistics were provided by the government. Next, in order to
      estimate any data discrepancy, the ratio of the cases recorded at clinics to the
      cases reported to the government was determined on the monthly basis. Finally,
      the associations between the monthly discrepancy and other variables were
      evaluated by a multiple regression analysis. RESULTS: The mean data discrepancy
      between the records of clinics and government statistics was 21.2% (n = 96).
      Significant associations were observed between the discrepancy and the average
      number of patients (coefficient: 0.05, 95%CI: 0.31, 0.07), illegible handwriting
      (coefficient: 0.09, 95%CI: 0.04, 0.15), the use of tally sheets (coefficient:
      0.38, 95%CI: -0.54, -0.22), and the clinic level (coefficient:-0.48, 95%CI:-0.89,
      0.06). CONCLUSION: The findings of this study demonstrate the huge data
      discrepancy between the records of clinics and government statistics in regard to
      clinical malaria case reporting. Moreover, the high numbers of patients,
      illegible writing, the disuse of tally sheets, and insufficient resources at some
      clinics are likely to be related to the increase in the discrepancy. The clinical
      malaria case reporting at the local clinic level therefore urgently needs
      improvement, in order to achieve both better malaria surveillance and to also
      eventually eliminate this disease in the Solomon Islands.

PMID- 19389240
TI  - Development and evaluation of an instrument for the critical appraisal of
      randomized controlled trials of natural products.
AB  - BACKGROUND: The efficacy of natural products (NPs) is being evaluated using
      randomized controlled trials (RCTs) with increasing frequency, yet a search of
      the literature did not identify a widely accepted critical appraisal instrument
      developed specifically for use with NPs. The purpose of this project was to
      develop and evaluate a critical appraisal instrument that is sufficiently
      rigorous to be used in evaluating RCTs of conventional medicines, and also has a
      section specific for use with single entity NPs, including herbs and natural
      sourced chemicals. METHODS: Three phases of the project included: 1) using
      experts and a Delphi process to reach consensus on a list of items essential in
      describing the identity of an NP; 2) compiling a list of non-NP items important
      for evaluating the quality of an RCT using systematic review methodology to
      identify published instruments and then compiling item categories that were part
      of a validated instrument and/or had empirical evidence to support their
      inclusion and 3) conducting a field test to compare the new instrument to a
      published instrument for usefulness in evaluating the quality of 3 RCTs of a NP
      and in applying results to practice. RESULTS: Two Delphi rounds resulted in a
      list of 15 items essential in describing NPs. Seventeen item categories fitting
      inclusion criteria were identified from published instruments for conventional
      medicines. The new assessment instrument was assembled based on content of the
      two lists and the addition of a Reviewer's Conclusion section. The field test of
      the new instrument showed good criterion validity. Participants found it useful
      in translating evidence from RCTs to practice. CONCLUSION: A new instrument for
      the critical appraisal of RCTs of NPs was developed and tested. The instrument is
      distinct from other available assessment instruments for RCTs of NPs in its
      systematic development and validation. The instrument is ready to be used by
      pharmacy students, health care practitioners and academics and will continue to
      be refined as required.

PMID- 19389241
TI  - Predictive models of insulin resistance derived from simple morphometric and
      biochemical indices related to obesity and the metabolic syndrome in baboons.
AB  - BACKGROUND: Non-human primates are valuable models for the study of insulin
      resistance and human obesity. In baboons, insulin sensitivity levels can be
      evaluated directly with the euglycemic clamp and is highly predicted by
      adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e.
      percent body fat by DXA and HbA1c). However, a simple method to screen and
      identify obese insulin resistant baboons for inclusion in interventional studies
      is not available. METHODS: We studied a population of twenty baboons with the
      euglycemic clamp technique to characterize a population of obese nondiabetic,
      insulin resistant baboons, and used a multivariate linear regression analysis
      (adjusted for gender) to test different predictive models of insulin sensitivity
      (insulin-stimulated glucose uptake = Rd) using abdominal circumference and
      fasting plasma insulin. Alternatively, we tested in a separate baboon population
      (n = 159), a simpler model based on body weight and fasting plasma glucose to
      predict the whole-body insulin sensitivity (Rd/SSPI) derived from the clamp.
      RESULTS: In the first model, abdominal circumference explained 59% of total
      insulin mediated glucose uptake (Rd). A second model, which included fasting
      plasma insulin (log transformed) and abdominal circumference, explained 64% of
      Rd. Finally, the model using body weight and fasting plasma glucose explained 51%
      of Rd/SSPI. Interestingly, we found that percent body fat was directly correlated
      with the adipocyte insulin resistance index (r = 0.755, p < 0.0001). CONCLUSION:
      In baboons, simple morphometric measurements of adiposity/obesity, (i.e.
      abdominal circumference), plus baseline markers of glucose/lipid metabolism,
      (i.e. fasting plasma glucose and insulin) provide a feasible method to screen and
      identify overweight/obese insulin resistant baboons for inclusion in
      interventional studies aimed to study human obesity, insulin resistance and type
      2 diabetes mellitus.

PMID- 19389242
TI  - A 96-well format for a high-throughput baculovirus generation, fast titering and
      recombinant protein production in insect and mammalian cells.
AB  - BACKGROUND: Baculovirus expression vector system (BEVS) has become a standard in
      recombinant protein production and virus-like particle preparation for numerous
      applications. FINDINGS: We describe here protocols which adapt baculovirus
      generation into 96-well format. CONCLUSION: The established methodology allows
      simple baculovirus generation, fast virus titering within 18 h and efficient
      recombinant protein production in a high-throughput format. Furthermore, the
      produced baculovirus vectors are compatible with gene expression in vertebrate
      cells in vitro and in vivo.

PMID- 19389243
TI  - Cervical cancer isolate PT3, super-permissive for adeno-associated virus
      replication, over-expresses DNA polymerase delta, PCNA, RFC and RPA.
AB  - BACKGROUND: Adeno-associated virus (AAV) type 2 is an important virus due to its
      use as a safe and effective human gene therapy vector and its negative
      association with certain malignancies. AAV, a dependo-parvovirus, autonomously
      replicates in stratified squamous epithelium. Such tissue occurs in the
      nasopharynx and anogenitals, from which AAV has been clinically isolated. Related
      autonomous parvoviruses also demonstrate cell tropism and preferentially
      replicate in oncogenically transformed cells. Combining these two attributes of
      parvovirus tropism, squamous and malignant, we assayed if AAV might replicate in
      squamous cervical carcinoma cell isolates. RESULTS: Three primary isolates (PT1
      3) and two established cervical cancer cell lines were compared to normal
      keratinocytes (NK) for their ability to replicate AAV. One isolate, PT3, allowed
      for high levels of AAV DNA replication and virion production compared to others.
      In research by others, four cellular components are known required for in vitro
      AAV DNA replication: replication protein A (RPA), replication factor C (RFC),
      proliferating cell nuclear antigen (PCNA), and DNA polymerase delta (POLD1).
      Thus, we examined PT3 cells for expression of these components by DNA microarray
      and real-time quantitative PCR. All four components were over-expressed in PT3
      over two representative low-permissive cell isolates (NK and PT1). However, this
      super-permissiveness did not result in PT3 cell death by AAV infection.
      CONCLUSION: These data, for the first time, provide evidence that these four
      cellular components are likely important for AAV in vivo DNA replication as well
      as in vitro. These data also suggest that PT3 will be a useful reagent for
      investigating the AAV-permissive transcriptome and AAV anti-cancer effect.

PMID- 19389244
TI  - A modified and automated version of the 'Fluorimetric Detection of Alkaline DNA
      Unwinding' method to quantify formation and repair of DNA strand breaks.
AB  - BACKGROUND: Formation and repair of DNA single-strand breaks are important
      parameters in the assessment of DNA damage and repair occurring in live cells.
      The 'Fluorimetric Detection of Alkaline DNA Unwinding (FADU)' method [Birnboim
      HC, Jevcak JJ. Cancer Res (1981) 41:1889-1892] is a sensitive procedure to
      quantify DNA strand breaks, yet it is very tedious to perform. RESULTS: In order
      (i) to render the FADU assay more convenient and robust, (ii) to increase
      throughput, and (iii) to reduce the number of cells needed, we have established a
      modified assay version that is largely automated and is based on the use of a
      liquid handling device. The assay is operated in a 96-well format, thus greatly
      increasing throughput. The number of cells required has been reduced to less than
      10,000 per data point. The threshold for detection of X-ray-induced DNA strand
      breaks is 0.13 Gy. The total assay time required for a typical experiment to
      assess DNA strand break repair is 4-5 hours. CONCLUSION: We have established a
      robust and convenient method measuring of formation and repair of DNA single
      strand breaks in live cells. While the sensitivity of our method is comparable to
      current assays, throughput is massively increased while operator time is
      decreased.

PMID- 19389245
TI  - The ANTOP study: focal psychodynamic psychotherapy, cognitive-behavioural
      therapy, and treatment-as-usual in outpatients with anorexia nervosa--a
      randomized controlled trial.
AB  - BACKGROUND: Anorexia nervosa is a serious eating disorder leading to high
      morbidity and mortality as a result of both malnutrition and suicide. The
      seriousness of the disorder requires extensive knowledge of effective treatment
      options. However, evidence for treatment efficacy in this area is remarkably
      weak. A recent Cochrane review states that there is an urgent need for large,
      well-designed treatment studies for patients with anorexia nervosa. The aim of
      this particular multi-centre study is to evaluate the efficacy of two
      standardized outpatient treatments for patients with anorexia nervosa: focal
      psychodynamic (FPT) and cognitive behavioural therapy (CBT). Each therapeutic
      approach is compared to a "treatment-as-usual" control group. METHODS/DESIGN: 237
      patients meeting eligibility criteria are randomly and evenly assigned to the
      three groups - two intervention groups (CBT and FPT) and one control group. The
      treatment period for each intervention group is 10 months, consisting of 40
      sessions respectively. Body weight, eating disorder related symptoms, and
      variables of therapeutic alliance are measured during the course of treatment.
      Psychotherapy sessions are audiotaped for adherence monitoring. The treatment in
      the control group, both the dosage and type of therapy, is not regulated in the
      study protocol, but rather reflects the current practice of established
      outpatient care. The primary outcome measure is the body mass index (BMI) at the
      end of the treatment (10 months after randomization). DISCUSSION: The study
      design surmounts the disadvantages of previous studies in that it provides a
      randomized controlled design, a large sample size, adequate inclusion criteria,
      an adequate treatment protocol, and a clear separation of the treatment
      conditions in order to avoid contamination. Nevertheless, the study has to deal
      with difficulties specific to the psychopathology of anorexia nervosa. The
      treatment protocol allows for dealing with the typically occurring medical
      complications without dropping patients from the protocol. However, because
      patients are difficult to recruit and often ambivalent about treatment, a drop
      out rate of 30% is assumed for sample size calculation. Due to the ethical
      problem of denying active treatment to patients with anorexia nervosa, the
      control group is defined as "treatment-as-usual".

PMID- 19389246
TI  - Effectiveness of the psychological and pharmacological treatment of
      catastrophization in patients with fibromyalgia: a randomized controlled trial.
AB  - BACKGROUND: Fibromyalgia is a prevalent and disabling disorder characterized by
      widespread pain and other symptoms such as insomnia, fatigue or depression.
      Catastrophization is considered a key clinical symptom in fibromyalgia; however,
      there are no studies on the pharmacological or psychological treatment of
      catastrophizing. The general aim of this study is to assess the effectiveness of
      cognitive-behaviour therapy and recommended pharmacological treatment for
      fibromyalgia (pregabalin, with duloxetine added where there is a comorbid
      depression), compared with usual treatment at primary care level. METHOD/DESIGN: 
      DESIGN: A multi-centre, randomized controlled trial involving three groups: the
      control group, consisting of usual treatment at primary care level, and two
      intervention groups, one consisting of cognitive-behaviour therapy, and the other
      consisting of the recommended pharmacological treatment for fibromyalgia.
      SETTING: 29 primary care health centres in the city of Zaragoza, Spain. SAMPLE:
      180 patients, aged 18-65 years, able to understand and read Spanish, who fulfil
      criteria for primary fibromyalgia, with no previous psychological treatment, and
      no pharmacological treatment or their acceptance to discontinue it two weeks
      before the onset of the study. INTERVENTION: Psychological treatment is based on
      the manualized protocol developed by Prof. Escobar et al, from the University of
      New Jersey, for the treatment of somatoform disorders, which has been adapted by
      our group for the treatment of fibromyalgia. It includes 10 weekly sessions of
      cognitive-behaviour therapy. Pharmacological therapy consists of the recommended
      pharmacological treatment for fibromyalgia: pregabalin (300-600 mg/day), with
      duloxetine (60-120 mg/day) added where there is a comorbid depression).
      MEASUREMENTS: The following socio-demographic data will be collected: sex, age,
      marital status, education, occupation and social class. The diagnosis of
      psychiatric disorders will be made with the Structured Polyvalent Psychiatric
      Interview. Other instruments to be administered are the Pain Catastrophizing
      Scale, the Hamilton tests for Anxiety and for Depression, the Fibromyalgia Impact
      Questionnaire (FIQ), the EuroQuol-5 domains (EQ-5D), and the use of health and
      social services (CSRI). Assessments will be carried out at baseline, 1, 3, and 6
      months. MAIN VARIABLE: Pain catastrophizing. ANALYSIS: The analysis will be per
      intent to treat. We will use the general linear models of the SPSS version 15
      statistical package, to analyse the effect of the treatment on the result
      variable (pain catastrophizing). DISCUSSION: It is necessary to assess the
      effectiveness of pharmacological and psychological treatments for pain
      catastrophizing in fibromyalgia. This randomized clinical trial will determine
      whether both treatments are effective for this important prognostic variable in
      patients with fibromyalgia. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN10804772.

PMID- 19389247
TI  - Clinical factors associated with a conservative gait pattern in older male
      veterans with diabetes.
AB  - BACKGROUND: Patients with diabetes and peripheral neuropathy are at higher risk
      for falls. People with diabetes sometimes adopt a more conservative gait pattern
      with decreased walking speed, widened base, and increased double support time.
      The purpose of this study was to use a multivariate approach to describe this
      conservative gait pattern. METHODS: Male veterans (mean age = 67 years; SD = 9.8;
      range 37-86) with diabetes (n = 152) participated in this study from July 2000 to
      May 2001 at the Veterans Affairs Medical Center, White River Junction, VT.
      Various demographic, clinical, static mobility, and plantar pressure measures
      were collected. Conservative gait pattern was defined by visual gait analysis as
      failure to demonstrate a heel-to-toe gait during the propulsive phase of gait.
      RESULTS: Patients with the conservative gait pattern had lower walking speed and
      decreased stride length compared to normal gait. (0.68 m/s v. 0.91 m/s, p <
      0.001; 1.04 m v. 1.24 m, p < 0.001) Age, monofilament insensitivity, and
      Romberg's sign were significantly higher; and ankle dorsiflexion was
      significantly lower in the conservative gait pattern group. In the multivariate
      analysis, walking speed, age, ankle dorsiflexion, and callus were retained in the
      final model describing 36% of the variance. With the inclusion of ankle
      dorsiflexion in the model, monofilament insensitivity was no longer an
      independent predictor. CONCLUSION: Our multivariate investigation of conservative
      gait in diabetes patients suggests that walking speed, advanced age, limited
      ankle dorsiflexion, and callus describe this condition more so than clinical
      measures of neuropathy.

PMID- 19389248
TI  - Modulation of immunity in young-adult and aged squirrel, Funambulus pennanti by
      melatonin and p-chlorophenylalanine.
AB  - BACKGROUND: Our interest was to find out whether pineal gland and their by
      melatonin act as modulator of immunosenescence. Parachlorophenylalanine (PCPA) -
      a beta adrenergic blocker, is known to perform chemical pinealectomy (Px) by
      suppressing indirectly the substrate 5-hydroxytryptamine (5-HT) for melatonin
      synthesis and thereby melatonin itself. The role of PCPA, alone and in
      combination with melatonin was recorded in immunomodulation and free radical load
      in spleen of young adult and aged seasonal breeder Indian palm squirrel
      Funambulus pennanti. RESULTS: Aged squirrel presented reduced immune parameters
      (i.e. total leukocyte count (TLC), Lymphocytes Count (LC), % stimulation ratio of
      splenocytes (% SR) against T cell mitogen concanavalin A (Con A), delayed type
      hypersensitivity (DTH) to oxazolone) when compared to young adult group.
      Melatonin administration (25 microg/100 g body mass/day) significantly increased
      the immune parameters in aged more than the young adult squirrel while PCPA
      administration (4.5 mg/100 g body mass/day) reduced all the immune parameters
      more significantly in young than aged. Combination of PCPA and melatonin
      significantly increased the immune parameters to the normal control level of both
      the age groups. TBARS level was significantly high in aged than the young group.
      PCPA treatment increased TBARS level of young and aged squirrels both while
      melatonin treatment decreased it even than the controls. Nighttime peripheral
      melatonin level was low in control aged group than the young group. Melatonin
      injection at evening hours significantly increased the peripheral level of
      nighttime melatonin, while combined injection of PCPA and melatonin brought it to
      control level in both aged and young adult squirrels. CONCLUSION: PCPA suppressed
      immune status more in aged than in adult by reducing melatonin level as it did
      chemical Px. Melatonin level decreased in control aged squirrels and so there was
      a decrease in immune parameters with a concomitant increase in free radical load
      of spleen. Decreased immune status can be restored following melatonin injection
      which decreased free radical load of spleen and suggest that immune organs of
      aged squirrels were sensitive to melatonin. Increased free radical load and
      decreased peripheral melatonin could be one of the reasons of immunosenescence.

PMID- 19389249
TI  - Narrowing the gap between eye care needs and service provision: the service
      training nexus.
AB  - BACKGROUND: The provision of eye care in the developing world has been
      constrained by the limited number of trained personnel and by professional
      cultures. The use of personnel with specific but limited training as members of
      multidisciplinary teams has become increasingly important as health systems seek
      to extract better value from their investments in personnel. Greater positive
      action is required to secure more efficient allocation of roles and resources.
      The supply of professional health workers is a factor of the training system, so
      it stands to reason that more cost-effective, flexible and available education
      methods are needed. This paper presents a highly flexible competencies-based
      multiple entry and exit training system that matches and adapts training to the
      prevailing population and service needs and demands, while lifting overall
      standards over time and highlighting the areas of potential benefit. METHODS:
      Literature surveys and interviews in five continents were carried out. Based on
      this and the author's own experience, a encies-based multiple entry and exit
      scheme for eye care in a developing country was derived, modeled and critically
      reviewed by interested parties in one country. RESULTS: The scheme was shown to
      be highly cost-effective and readily adaptable to the anticipated eye care needs
      of the population. Eye care players in one selected country have commented
      favourably on the scheme. CONCLUSION: The underlying principles used to derive
      this model can be applied to many eye care systems in many developing countries.
      The model can be used in other disciplines with similar constructs to eye care.

PMID- 19389250
TI  - PAS staining of bronchoalveolar lavage cells for differential diagnosis of
      interstitial lung disease.
AB  - Bronchoalveolar lavage (BAL) is a useful diagnostic tool in interstitial lung
      diseases (ILD). However, differential cell counts are often non specific and
      immunocytochemistry is time consuming. Staining of glycoproteins by periodic acid
      Schiff (PAS) reaction may help in discriminating different forms of ILD. In
      addition, PAS staining is easy to perform. BAL cells from patients with
      idiopathic pulmonary fibrosis (IPF) (n = 8), sarcoidosis (n = 9), and extrinsic
      allergic alveolitis (EAA) (n = 2) were investigated. Cytospins from BAL cells
      were made and cells were stained using Hemacolor quick stain and PAS staining.
      Lymphocytic alveolitis was found in sarcoidosis and EAA whereas in IPF both
      lymphocytes and neutrophils were increased. PAS positive cells were significantly
      decreased in EAA compared to IPF and sarcoidosis (25.5% +/- 0.7% vs 59.8% +/-
      25.1% and 64.0% +/- 19.7%, respectively) (P < 0.05). No significant correlation
      between PAS positive cells and inflammatory cells was observed. These results
      suggest that PAS staining of BAL cells may provide additional information in the
      differential diagnosis of ILD. Further studies ware warranted to evaluate PAS
      staining in larger numbers of BAL from patients with ILD.

PMID- 19389251
TI  - Medicinal plants used by the Yi ethnic group: a case study in central Yunnan.
AB  - BACKGROUND: This paper is based on ethnomedicinal investigation conducted from
      1999-2002 in Chuxiong, central Yunnan Province, Southwest China. The Yi medicine
      has made a great contribution to the ethnomedicinal field in China. Neither case
      studies nor integrated inventories have previously been conducted to investigate
      the traditional Yi plants. This paper aims to argue the status and features of
      medicinal plants used in traditional Yi societies through a case study. METHODS:
      The approaches of ethnobotany, anthropology, and participatory rural appraisal
      were used in the field surveys. Twenty-two informants in four counties were
      interviewed during eight field trips. Medicinal plant specimens were identified
      according to taxonomic methods. RESULTS: One hundred sixteen medicinal plant
      species were found to be useful by the local people in the treatment of various
      diseases or disorders, especially those relating to trauma, gastrointestinal
      disorders and the common cold. Among these 116 species, 25 species (21.55%) were
      found to have new curative effects and 40 species (34.48%) were recorded for
      their new preparation methods; 55 different species were used in treating wounds
      and fractures, and 47 were used to treat gastrointestinal disorders. Traditional
      Yi herbal medicines are characterized by their numerous quantities of herbaceous
      plants and their common preparation with alcohol. CONCLUSION: Totally 116 species
      in 58 families of medicinal plants traditionally used by the Yi people were
      inventoried and documented. The characteristics of medicinal plants were
      analyzed. Some new findings (such as new curative effects and new preparation
      methods) were recorded These newly gathered ethnobotanical and medicinal data are
      precious sources for the future development of new drugs, and for further
      phytochemical, pharmacological and clinical studies.

PMID- 19389252
TI  - Stilbene glycosides are natural product inhibitors of FGF-2-induced angiogenesis.
AB  - BACKGROUND: Angiogenesis, the growth of new blood vessels from the pre-existing
      vasculature is associated with pathological processes, in particular tumour
      development, and is a target for the development of new therapies. We have
      investigated the anti-angiogenic potential of two naturally occurring stilbene
      glycosides (compounds 1 and 2) isolated from the medicinal plant Boswellia
      papyriferai using large and smallvessel-derived endothelial cells. Compound 1
      (trans-4',5'-dihydroxy-3-methoxystilbene-5-O-{alpha-L-rhamnopyranosyl-(1-->2)
      [alpha-L-rhamnopyranosyl-(1-->6)}-beta-D-glucopyranoside was the more hydrophilic
      and inhibited FGF-2-induced proliferation, wound healing, invasion in Matrigel,
      tube formation and angiogenesis in large and small vessel-derived endothelial
      cells and also in the chick chorioallantoic membrane assay. Using a binding assay
      we were able to show compound 1 reduced binding of FGF-2 to fibroblast growth
      factor receptors-1 and -2. In all cases the concentration of compound 1 which
      caused 50% inhibition (IC50) was determined. The effect of compound 1 on EGF and
      VEGF-induced proliferation was also investigated. RESULTS: Compound 1 inhibited
      all stages of FGF-2 induced angiogenesis with IC50 values in the range 5.8 +/-
      0.18 - 48.90 +/- 0.40 microM but did not inhibit EGF or VEGF-induced
      angiogenesis. It also inhibited FGF-2 binding to FGF receptor-1 and -2 with IC50
      values of 5.37 +/- 1.04 and 9.32 +/- 0.082 muM respectively and with concommotant
      down-regulation of phosphorylated-ERK-1/-2 expression. Compound 2 was an
      ineffective inhibitor of angiogenesis despite its structural homology to compound
      1. CONCLUSION: Compound 1 inhibited FGF-2 induced angiogenesis by binding to its
      cognate receptors and is an addition to the small number of natural product
      inhibitors of angiogenesis.

PMID- 19389253
TI  - Nanoparticle penetration and transport in living pumpkin plants: in situ
      subcellular identification.
AB  - BACKGROUND: In recent years, the application of nanotechnology in several fields
      of bioscience and biomedicine has been studied. The use of nanoparticles for the
      targeted delivery of substances has been given special attention and is of
      particular interest in the treatment of plant diseases. In this work both the
      penetration and the movement of iron-carbon nanoparticles in plant cells have
      been analyzed in living plants of Cucurbita pepo. RESULTS: The nanoparticles were
      applied in planta using two different application methods, injection and
      spraying, and magnets were used to retain the particles in movement in specific
      areas of the plant. The main experimental approach, using correlative light and
      electron microscopy provided evidence of intracellular localization of
      nanoparticles and their displacement from the application point. Long range
      movement of the particles through the plant body was also detected, particles
      having been found near the magnets used to immobilize and concentrate them.
      Furthermore, cell response to the nanoparticle presence was detected. CONCLUSION:
      Nanoparticles were capable of penetrating living plant tissues and migrating to
      different regions of the plant, although movements over short distances seemed to
      be favoured. These findings show that the use of carbon coated magnetic particles
      for directed delivery of substances into plant cells is a feasible application.

PMID- 19389255
TI  - The effect of follicular fluid hormones on oocyte recovery after ovarian
      stimulation: FSH level predicts oocyte recovery.
AB  - BACKGROUND: Ovarian stimulation for assisted reproductive technology (ART)
      overcomes the physiologic process to develop a single dominant follicle. However,
      following stimulation, egg recovery rates are not 100%. The objective of this
      study is to determine if the follicular fluid hormonal environment is associated
      with oocyte recovery. METHODS: This is a prospective study involving patients
      undergoing ART by standard ovarian stimulation protocols at an urban academic
      medical center. A total of 143 follicular fluid aspirates were collected from 80
      patients. Concentrations of FSH, hCG, estradiol, progesterone, testosterone and
      prolactin were determined. A multivariable regression analysis was used to
      investigate the relationship between the follicular fluid hormones and oocyte
      recovery. RESULTS: Intrafollicular FSH was significantly associated with oocyte
      recovery after adjustment for hCG (Adjusted odds ratio (AOR) = 1.21, 95%CI 1.03
      1.42). The hCG concentration alone, in the range tested, did not impact the odds
      of oocyte recovery (AOR = 0.99, 95%CI 0.93-1.07). Estradiol was significantly
      associated with oocyte recovery (AOR = 0.98, 95% CI 0.96-0.99). After adjustment
      for progesterone, the strength of association between FSH and oocyte recovery
      increased (AOR = 1.84, 95%CI 1.45-2.34). CONCLUSION: The relationship between FSH
      and oocyte recovery is significant and appears to work through mechanisms
      independent of the sex hormones. FSH may be important for the physiologic event
      of separation of the cumulus-oocyte complex from the follicle wall, thereby
      influencing oocyte recovery. Current methods for inducing the final stages of
      oocyte maturation, with hCG administration alone, may not be optimal.
      Modifications of treatment protocols utilizing additional FSH may enhance oocyte
      recovery.

PMID- 19389254
TI  - Placental biomarkers of phthalate effects on mRNA transcription: application in
      epidemiologic research.
AB  - BACKGROUND: CYP19 and PPARgamma are two genes expressed in the placental
      trophoblast that are important to placental function and are disrupted by
      phthalate exposure in other cell types. Measurement of the mRNA of these two
      genes in human placental tissue by quantitative real-time polymerase chain
      reaction (qPCR) offers a source of potential biomarkers for use in epidemiologic
      research. We report on methodologic challenges to be considered in study design.
      METHODS: We anonymously collected 10 full-term placentas and, for each, sampled
      placental villi at 12 sites in the chorionic plate representing the inner (closer
      to the cord insertion site) and outer regions. Each sample was analyzed for the
      expression of two candidate genes, aromatase (CYP19) and peroxisome proliferator
      activated receptor protein gamma (PPARgamma) and three potential internal
      controls: cyclophilin (CYC), 18S rRNA (18S), and total RNA. Between and within
      placenta variability was estimated using variance component analysis.
      Associations of expression levels with sampling characteristics were estimated
      using mixed effects models. RESULTS: We identified large within-placenta
      variability in both transcripts (>90% of total variance) that was minimized to
      <20% of total variance by using 18S as an internal control and by modelling the
      means by inner and outer regions. 18S rRNA was the most appropriate internal
      control based on within and between placenta variability estimates and low
      correlations of 18S mRNA with target gene mRNA. Gene expression did not differ
      significantly by delivery method. We observed decreases in the expression of both
      transcripts over the 25 minute period after delivery (CYP19 p-value for trend =
      0.009 and PPARgamma (p-value for trend = 0.002). Using histologic methods, we
      confirmed that our samples were comprised predominantly of villous tissue of the
      fetal placenta with minimal contamination of maternally derived cell types.
      CONCLUSION: qPCR-derived biomarkers of placental CYP19 and PPARgamma gene
      expression show high within-placental variability. Sampling scheme, selection of
      an appropriate internal control and the timing of sample collection relative to
      delivery can be optimized to minimize within-placenta and other sources of
      underlying, non-etiologic variability.

PMID- 19389256
TI  - Liver-enriched transcription factors are critical for the expression of
      hepatocyte marker genes in mES-derived hepatocyte-lineage cells.
AB  - BACKGROUND: Induction of stem cell differentiation toward functional hepatocytes
      is hampered by lack of knowledge of the hepatocyte differentiation processes. The
      overall objective of this project is to characterize key stages in the hepatocyte
      differentiation process. RESULTS: We established a mouse embryonic stem (mES)
      cell culture system which exhibited changes in gene expression profiles similar
      to those observed in the development of endodermal and hepatocyte-lineage cells
      previously described in the normal mouse embryo. Transgenic mES cells were
      established that permitted isolation of enriched hepatocyte-lineage populations.
      This approach has isolated mES-derived hepatocyte-lineage cells that express
      several markers of mature hepatocytes including albumin, glucose-6-phosphatase,
      tyrosine aminotransferase, cytochrome P450-3a, phosphoenolpyruvate carboxykinase
      and tryptophan 2,3-dioxygenase. In addition, our results show that the up
      regulation of the expression levels of hepatocyte nuclear factor-3alpha, -4alpha,
      -6, and CCAAT-enhancer binding protein-beta might be critical for passage into
      late-stage differentiation towards functional hepatocytes. These data present
      important steps for definition of regulatory phenomena that direct specific cell
      fate determination. CONCLUSION: The mES cell culture system generated in this
      study provides a model for studying transition between stages of the hepatocyte
      development and has significant potential value for studying the molecular basis
      of hepatocyte differentiation in vitro.

PMID- 19389257
TI  - Insecticide resistance profiles for malaria vectors in the Kassena-Nankana
      district of Ghana.
AB  - BACKGROUND: Malaria is a major public health problem in Ghana. The current
      strategy of the National Malaria Control Programme is based on effective case
      management and the use of insecticide treated bed nets among vulnerable groups
      such as children under-five years of age and pregnant women. Resistance to
      pyrethroids by Anopheles gambiae s.l. and Anopheles funestus has been reported in
      several African countries including neighbouring Burkina Faso. METHODS: Indoor
      resting Anopheles mosquitoes were collected. Blood-fed and gravid females were
      allowed to oviposit, eggs hatched and larvae reared to 1-3 days old adults and
      tested against permethrin 0.75%, deltamethrin 0.05%, cyfluthrin 0.15%,
      lambdacyhalothrin 0.1% and DDT 4%, based on WHO methodology. PCR analyses were
      carried out on a sub-sample of 192 of the An. gambiae for sibling species complex
      determination. Resistance to pyrethroids and DDT was determined by genotyping the
      knock-down resistance kdr gene mutations in the study area. RESULTS: A total of
      9,749 1-3 days-old F1 female Anopheles mosquitoes were exposed to the
      insecticides. Among the pyrethroids, permethrin, 0.75% had the least knockdown
      effect, whilst cyfluthrin 0.15%, had the highest knock-down effect. Overall, no
      difference in susceptibility between An. gambiae 93.3% (95% CI: 92.5-94.1) and
      An. funestus 94.5% (95% CI: 93.7-95.3) was observed when exposed to the
      pyrethroids. Similarly, there was no difference in susceptibility between the two
      vector species (An. gambiae = 79.1% (95% CI: 76.6-81.8) and An. funestus = 83.5%
      (95% CI: 80.2-86.4) when exposed to DDT. Overall susceptibility to the
      insecticides was between 80% and 98%, suggesting that there is some level of
      resistance, except for cyfluthrin 0.15%. The kdr PCR assay however, did not
      reveal any kdr mutations. The analysis also revealed only the molecular M (Mopti)
      form. CONCLUSION: The findings in this study show that An. gambiae and An.
      funestus, the main malaria vector mosquitoes in the Kassena-Nankana district are
      susceptible to the insecticides being used in the treatment of bed nets in the
      malaria control programme. There is however, the need for continuous monitoring
      of the pyrethroids as the efficacy is not very high.

PMID- 19389258
TI  - Single-embryo transfer reduces clinical pregnancy rates and live births in fresh
      IVF and Intracytoplasmic Sperm Injection (ICSI) cycles: a meta-analysis.
AB  - BACKGROUND: It has become an accepted procedure to transfer more than one embryo
      to the patient to achieve acceptable ongoing pregnancy rates. However, transfers
      of more than a single embryo increase the probability of establishing a multiple
      gestation. Single-embryo transfer can minimize twin pregnancies but may also
      lower live birth rates. This meta-analysis aimed to compare current data on
      single-embryo versus double-embryo transfer in fresh IVF/ICSI cycles with respect
      to implantation, ongoing pregnancy and live birth rates. METHODS: Search
      strategies included on-line surveys of databases from 1995 to 2008. Data
      management and analysis were conducted using the Stats Direct statistical
      software. The fixed-effect model was used for odds ratio (OR). Fixed-effect
      effectiveness was evaluated by the Mantel Haenszel method. Seven trials fulfilled
      the inclusion criteria. RESULTS: When pooling results under the fixed-effect
      model, the implantation rate was not significantly different between double
      embryo transfer (34.5%) and single-embryo transfer group (34.7%) (P = 0.96; OR =
      0.99, 95% CI 0.78, 1.25). On the other hand, double-embryo transfer produced a
      statistically significantly higher ongoing clinical pregnancy rate (44.5%) than
      single-embryo transfer (28.3%) (P < 0.0001; OR:2.06, 95% CI = 1.64,2.60). At the
      same time, pooling results presented a significantly higher live birth rate when
      double-embryo transfer (42.5%) (P < 0.001; OR: 1.87, 95% CI = 1.44,2.42) was
      compared with single-embryo transfer (28.4%). CONCLUSION: Meta-analysis with 95%
      confidence showed that, despite similar implantation rates, fresh double-embryo
      transfer had a 1.64 to 2.60 times greater ongoing pregnancy rate and 1.44 to 2.42
      times greater live birth rate than single-embryo transfer in a population
      suitable for ART treatment.

PMID- 19389259
TI  - Common cortical responses evoked by appearance, disappearance and change of the
      human face.
AB  - BACKGROUND: To segregate luminance-related, face-related and non-specific
      components involved in spatio-temporal dynamics of cortical activations to a face
      stimulus, we recorded cortical responses to face appearance (Onset),
      disappearance (Offset), and change (Change) using magnetoencephalography.
      RESULTS: Activity in and around the primary visual cortex (V1/V2) showed
      luminance-dependent behavior. Any of the three events evoked activity in the
      middle occipital gyrus (MOG) at 150 ms and temporo-parietal junction (TPJ) at 250
      ms after the onset of each event. Onset and Change activated the fusiform gyrus
      (FG), while Offset did not. This FG activation showed a triphasic waveform,
      consistent with results of intracranial recordings in humans. CONCLUSION:
      Analysis employed in this study successfully segregated four different elements
      involved in the spatio-temporal dynamics of cortical activations in response to a
      face stimulus. The results show the responses of MOG and TPJ to be associated
      with non-specific processes, such as the detection of abrupt changes or exogenous
      attention. Activity in FG corresponds to a face-specific response recorded by
      intracranial studies, and that in V1/V2 is related to a change in luminance.

PMID- 19389260
TI  - The roles of ASK family proteins in stress responses and diseases.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated
      protein kinase kinase kinase family, which activates c-Jun N-terminal kinase and
      p38 in response to a diverse array of stresses such as oxidative stress,
      endoplasmic reticulum stress and calcium influx. In the past decade, various
      regulatory mechanisms of ASK1 have been elucidated, including its oxidative
      stress-dependent activation. Recently, it has emerged that ASK family proteins
      play key roles in cancer, cardiovascular diseases and neurodegenerative diseases.
      In this review, we summarize the recent findings on ASK family proteins and their
      implications in various diseases.

PMID- 19389261
TI  - Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of
      related enzymes, and risk of breast cancer: a case-control study in Brazilian
      women.
AB  - BACKGROUND: Several studies have determined that dietary intake of B vitamins may
      be associated with breast cancer risk as a result of interactions between 5,10
      methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) in the
      one-carbon metabolism pathway. However, the association between B vitamin intake
      and breast cancer risk in Brazilian women in particular has not yet been
      investigated. METHODS: A case-control study was conducted in Sao Paulo, Brazil,
      with 458 age-matched pairs of Brazilian women. Energy-adjusted intakes of folate,
      vitamin B6, and vitamin B12 were derived from a validated Food Frequency
      Questionnaire (FFQ). Genotyping was completed for MTHFR A1298C and C677T, and MTR
      A2756G polymorphisms. A logistical regression model was used to calculate odds
      ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Neither dietary
      intake of folate, vitamin B6, or vitamin B12 nor MTHFR polymorphisms were
      independently associated with breast cancer risk. Analysis stratified by
      menopausal status showed a significant association between placement in the
      highest tertile of folate intake and risk of breast cancer in premenopausal women
      (OR = 2.17, 95% CI: 1.23-3.83; P trend = 0.010). The MTR 2756GG genotype was
      associated with a higher risk of breast cancer than the 2756AA genotype (OR =
      1.99, 95% CI = 1.01-3.92; P trend = 0.801), and statistically significant
      interactions with regard to risk were observed between the MTHFR A1298C
      polymorphism and folate (P = 0.024) or vitamin B6 (P = 0.043), and between the
      MTHFR C677T polymorphism and folate (P = 0.043) or vitamin B12 (P = 0.022).
      CONCLUSION: MTHFR polymorphisms and dietary intake of folate, vitamin B6, and
      vitamin B12 had no overall association with breast cancer risk. However,
      increased risk was observed in total women with the MTR 2756GG genotype and in
      premenopausal women with high folate intake. These findings, as well as
      significant interactions between MTHFR polymorphisms and B vitamins, warrant
      further investigation.

PMID- 19389262
TI  - The design and protocol of acupuncture for migraine prophylaxis: a multicenter
      randomized controlled trial.
AB  - BACKGROUND: Many studies have already reported encouraging results in the
      prophylactic therapy of migraine by acupuncture, but there seems to be a lack of
      high quality randomized controlled trials from China. We design and perform a
      randomized controlled clinical trial to evaluate the efficacy of acupuncture
      compared with flunarizine in the prophylactic therapy of patients with migraine
      without aura in China. METHODS: This trial is a multicenter, prospective,
      randomized controlled clinical trial. The 140 migraine patients are randomly
      allocated to two different groups. The acupuncture groups (n = 70) is treated
      with acupuncture and placebo medicine; while the control group (n = 70) is
      treated with sham acupuncture and medicine (Flunarizine). Both Flunarizine and
      placebo are taken 10 mg once per night for the first 2 weeks and then 5 mg once
      per night for the next 2 weeks. Patients in both groups receive 12 sessions of
      verum/sham acupuncture in 4 weeks. DISCUSSION: The study design and the long term
      clinical practice of acupuncturists guarantee a high external validity for the
      results. The results of our trial will be helpful to supply the evidence on the
      efficacy of acupuncture for migraine prophylaxis in China.

PMID- 19389263
TI  - Investigation on the role of nsSNPs in HNPCC genes--a bioinformatics approach.
AB  - BACKGROUND: A central focus of cancer genetics is the study of mutations that are
      causally implicated in tumorigenesis. The identification of such causal mutations
      not only provides insight into cancer biology but also presents anticancer
      therapeutic targets and diagnostic markers. Missense mutations are nucleotide
      substitutions that change an amino acid in a protein, the deleterious effects of
      these mutations are commonly attributed to their impact on primary amino acid
      sequence and protein structure. METHODS: The method to identify functional SNPs
      from a pool, containing both functional and neutral SNPs is challenging by
      experimental protocols. To explore possible relationships between genetic
      mutation and phenotypic variation, we employed different bioinformatics
      algorithms like Sorting Intolerant from Tolerant (SIFT), Polymorphism Phenotyping
      (PolyPhen), and PupaSuite to predict the impact of these amino acid substitutions
      on protein activity of mismatch repair (MMR) genes causing hereditary
      nonpolyposis colorectal cancer (HNPCC). RESULTS: SIFT classified 22 of 125
      variants (18%) as 'Intolerant." PolyPhen classified 40 of 125 amino acid
      substitutions (32%) as "Probably or possibly damaging". The PupaSuite predicted
      the phenotypic effect of SNPs on the structure and function of the affected
      protein. Based on the PolyPhen scores and availability of three-dimensional
      structures, structure analysis was carried out with the major mutations that
      occurred in the native protein coded by MSH2 and MSH6 genes. The amino acid
      residues in the native and mutant model protein were further analyzed for solvent
      accessibility and secondary structure to check the stability of the proteins.
      CONCLUSION: Based on this approach, we have shown that four nsSNPs, which were
      predicted to have functional consequences (MSH2-Y43C, MSH6-Y538S, MSH6-S580L, and
      MSH6-K854M), were already found to be associated with cancer risk. Our study
      demonstrates the presence of other deleterious mutations and also endorses with
      in vivo experimental studies.

PMID- 19389264
TI  - Mapping quantitative trait loci (QTL) in sheep. I. A new male framework linkage
      map and QTL for growth rate and body weight.
AB  - A male sheep linkage map comprising 191 microsatellites was generated from a
      single family of 510 Awassi-Merino backcross progeny. Except for ovine
      chromosomes 1, 2, 10 and 17, all other chromosomes yielded a LOD score difference
      greater than 3.0 between the best and second-best map order. The map is on
      average 11% longer than the Sheep Linkage Map v4.7 male-specific map. This map
      was employed in quantitative trait loci (QTL) analyses on body-weight and growth
      rate traits between birth and 98 weeks of age. A custom maximum likelihood
      program was developed to map QTL in half-sib families for non-inbred strains (QTL
      MLE) and is freely available on request. The new analysis package offers the
      advantage of enabling QTL x fixed effect interactions to be included in the
      model. Fifty-four putative QTL were identified on nine chromosomes. Significant
      QTL with sex-specific effects (i.e. QTL x sex interaction) in the range of 0.4 to
      0.7 SD were found on ovine chromosomes 1, 3, 6, 11, 21, 23, 24 and 26.

PMID- 19389265
TI  - Factors affecting quality-of-life impact of adult tonsillectomy.
AB  - OBJECTIVE: To assess the quality of life of adult patients with recurrent
      tonsillitis after tonsillectomy, and to determine predictive factors for patient
      satisfaction. METHODS: In a prospective cohort study, a Glasgow benefit inventory
      questionnaire was posted to 70 adult patients six months after tonsillectomy for
      recurrent tonsillitis. Data were obtained on patient characteristics, risk
      factors, tonsillitis history, and clinical and operative findings. The patients
      were also assessed using self-completed diary data collection regarding acute
      symptoms (i.e. fever, throat pain, cough and rhinitis), tonsillitis episodes and
      visits to a doctor, either three to six months before tonsillectomy or six months
      after tonsillectomy. Predictive factors were sought for inclusion in the worst
      30th percentile of patients (i.e. Glasgow benefit inventory score under 18),
      regarding post-operative change in quality of life. RESULTS: Sixty-two patients
      (40 females, 22 males; age range 15-46 years) returned the questionnaire
      (response rate 89 per cent). The mean total Glasgow benefit inventory score after
      tonsillectomy was +26 (standard deviation 14). The mean scores for Glasgow
      benefit inventory subscales were: general health +25 (standard deviation 18),
      social functioning +5 (standard deviation 14) and physical functioning +55
      (standard deviation 23). The only factors associated with low patient
      satisfaction were a small number of tonsillitis episodes (diary-based data) and
      days with fever before tonsillectomy. CONCLUSIONS: Adult patients with recurrent
      tonsillitis seemed to be generally pleased with their tonsillectomy. The more
      symptoms they had prior to surgery, the greater was their improvement in quality
      of life. No other patient- or disease-related factors were associated with
      patient satisfaction.

PMID- 19389266
TI  - Initial outcomes from universal newborn hearing screening in Avon.
AB  - OBJECTIVE: The Avon Area Health Authority was a first-phase site for introduction
      of universal newborn screening in the UK. The aims of this study were: to review
      the programme's results to date; to assess the impact screening would have on
      other services (e.g. the cochlear implant programme); and to assess the longer
      term outcome for children identified by the screening programme. PATIENTS: All
      children identified by the Avon universal newborn hearing screening programme
      between April 2002 and July 2006. RESULTS: Fifty-four children with a bilateral
      hearing impairment of worse than 40 dBHL were identified from a screened
      population of approximately 44 000. Nine of these children were put forward for
      cochlear implantation, and seven had been implanted at the time of writing.
      Thirteen of these children were identified with possible auditory neuropathy or
      dys-synchrony. All the newborn hearing screening programme criteria assessed were
      met. CONCLUSIONS: The screening programme was effective. Some areas may need
      review in order to optimise patient care.

PMID- 19389267
TI  - Skin incisions for the excision of spherical cutaneous and subcutaneous lesions.
AB  - Spherical cutaneous and subcutaneous lesions such as sebaceous cysts are often
      removed via an ellipse, particularly if they are relatively large. Deciding the
      width of the ellipse can be difficult. We calculated that if the width of the
      ellipse is one-third of the half circumference, then the wound should close
      satisfactorily.

PMID- 19389268
TI  - Trichinellosis survey in the wild boar from the Toledo mountains in south-western
      Spain (2007-2008): molecular characterization of Trichinella isolates by ISSR
      PCR.
AB  - In Spain, trichinellosis represents a public health problem, with an average of
      five outbreaks per year, wild boar meat being the main source of infection. A
      trichinellosis survey (2007-2008 hunting campaign) was carried out on wild boars
      in the Toledo Mountains (south-western Spain, EU) in the context of a
      surveillance programme on wildlife diseases. A total of 2216 wild boars from
      different locations of the region were examined. The examination was carried out
      by veterinarians in the local abattoir (Matadero Municipal de Toledo). The
      positive samples were sent to the Department of Parasitology (Facultad de
      Farmacia, UCM) for experimental isolation and specific identification by inter
      simple sequence repeat-polymerase chain reaction (ISSR-PCR). Using this technique
      we identified 17 isolates as Trichinella spiralis with an electrophoretic profile
      indistinguishable from the T. spiralis reference strain (ISS48). We confirmed
      that ISSR-PCR is a robust technique for the molecular identification of
      Trichinella isolates. According to our results, the prevalence of T. spiralis in
      wild boars from the Toledo Mountains (>800 m above sea level) during the hunting
      season was approximately 0.77%. The prevalence of T. spiralis (100% of our
      observations) is a good example of the persistence of this species in sylvatic
      conditions (coming from the domestic cycle), if a good wild host is abundant. Our
      observations confirm the major prevalence of T. spiralis over T. britovi in this
      region, as well as the risk to human health represented by the consumption of
      uninspected wild boar meat.

PMID- 19389269
TI  - Use of mitochondrial RNA genes for the differentiation of four Trichinella
      species by multiplex PCR amplification.
AB  - Until now, four species of the Trichinella genus have been identified in Europe:
      Trichinella spiralis, T. nativa, T. britovi and T. pseudospiralis. The aim of
      this work was to establish a sound polymerase chain reaction (PCR)-based method
      to differentiate these four species using mitochondrial rDNA as a reliable
      genetic marker and to evaluate the sensitivity of this method. Full-length DNA
      sequences coding for the small and large mitochondrial rRNA (mt-rrnS and mt-rrnL)
      of the four species are described. A multiplex PCR was designed and successfully
      tested on 24 European isolates. As few as one larva, or 100 pg of genomic DNA was
      detected, providing equivalent sensitivity to previously described PCR methods.
      The PCR-based method of mitochondrial rDNA amplification was thereby established
      as a sensitive and reproductive diagnostic method for the four European
      Trichinella species.

PMID- 19389270
TI  - Amino acid carryover in the subzonal space of mouse fertilized ova affects
      subsequent transport kinetics.
AB  - SummaryWe have investigated whether culture in glycine-containing medium affects
      subsequent glycine transport by the specific transport system, GLYT1, which is
      the sole glycine transporter in fertilized mouse ova. When fertilized ova were
      maintained for 6 h in culture with a physiological level of glycine (1 mM),
      subsequent transport of radiolabelled glycine was decreased by 40% compared with
      fertilized ova that had been maintained in glycine-free medium. Kinetic
      measurements showed that the apparent glycine affinity was decreased after
      culture with glycine (Km increased from 0.20 to 0.41 mM), but maximal transport
      rate was unchanged (similar Vmax of 20 and 23 fmol/fertilized ovum/min). These
      findings could have reflected activation of GLYT1 by prolonged substrate
      starvation, similar to some other amino acid transport systems. However, our
      findings were instead consistent with the alteration in glycine transport being
      due to trapping of glycine within the zona pellucida resulting in competitive
      transport inhibition even after ova were removed from glycine-containing media.
      First, even very brief exposures to glycine resulted in decreased subsequent
      glycine transport rates, with a maximal effect apparent within ~6 min. Second,
      extensive washing (at least six) reversed the effect. Third, the effect was
      absent when zona-free fertilized ova were used. Thus, it appears that components
      of the external environment of preimplantation embryos may continue to affect
      transport kinetics for a period even after embryos are removed from environments
      that contain them.

PMID- 19389271
TI  - Diethyldithiocarbamate potentiates the effects of protamine sulphate in the
      isolated rat uterus.
AB  - Protamine sulphate causes potassium ion channel-mediated relaxation of
      spontaneous and calcium ion-induced contractions of the isolated rat uterus.
      Diethyldithiocarbamate (DDC) potentiated the effect of protamine sulphate. A
      mechanism for DDC's action was postulated on the basis of its interactions with
      divalent iron ions and Cu,Zn-SOD. DDC chelates divalent iron ions creating DDC
      iron (Fe-DDC) complexes. Fe-DDC forms stable NO-Fe-DDC(2) complexes by NO
      scavenging and de-nitrosylation processes, which in combination with DDC (5 mM)
      provoke inhibition of Cu,Zn-SOD resulting in specific oxidative conditions
      culminating in potassium ion channel opening, membrane hyperpolarisation,
      inhibition of calcium ion influx and subsequent muscle relaxation. As Fe-DDC and
      NO-Fe-DDC(2) complexes exclude divalent iron ions from participating in the
      hydroxyl radical generating Fenton reaction, DDC can also prevent iron-related
      pathophysiological manifestations. Such permissive roles of DDC open the
      possibility for application of its pharmacological form (disulfiram) to a wider
      spectrum of pathophysiological conditions related to smooth muscles.

PMID- 19389272
TI  - Atherothrombosis and oxidative stress: the connection and correlation in
      diabetes.
AB  - BACKGROUND: Hyperglycaemia-induced depletion of reduced glutathione (GSH) causes
      erythrocyte oxidative stress (EOS), which leads to vascular events including
      exacerbation of thrombotic events evidenced by changes in D-dimer level. It
      would, therefore, appear that there is a complex link between GSH and D-dimer,
      which are part of an emerging array of biomarkers associated with diabetes. The
      objective of this study was to investigate evidence of correlation between levels
      of plasma D-dimer and erythrocyte GSH in diabetes disease progression. SUBJECTS
      AND METHODS: A cohort of 69 subjects were selected based on medical history plus
      clinical findings and equally divided into control, prediabetes and diabetes
      groups, matched for age and sex. Plasma D-dimer and erythrocyte reduced
      glutathione (GSH) were determined and separated into quartiles as a means of
      indicating disease severity. Statistical analysis was by Pearson's correlation
      coefficient. RESULTS: Of the three groups, only the diabetes group showed any
      correlation between GSH and D-dimer. Of importance is that for increasing GSH,
      the second quartile range of GSH (xbar +/- SD = 45 +/- 22 mg/100ml) showed a
      statistically significant negative correlation for ranked D-dimer (xbar +/- SD =
      1055 +/- 828 microg/l; r = -0.88; P < 0.02). The fourth quartile GSH range (xbar
      +/- SD = 79 +/- 40 mg/100 ml) showed a statistically significant positive
      correlation with D-dimer (xbar +/- SD = 1055 +/- 828 microg/l; r = 0.91; P <
      0.02). Thus, within the diabetes group only, the increasing level of oxidative
      stress as measured by GSH first indicates a reduction in D-dimer followed by a
      rise in D-dimer, which led to the proposal of a two-part process of
      atherosclerosis that reconciles previous contradictory findings. CONCLUSIONS:
      This study provides not only evidence of a correlation between oxidative stress
      level and fibrinolysis in diabetes, but also an explanation of why previous
      studies have found both hypo- or hyperfibrinolysis associated with diabetes.

PMID- 19389273
TI  - Effects of pregnenolone-16alpha-carbonitrile on vitamin E status and protein
      levels of antioxidant enzymes in male rats fed a vitamin E-supplemented diet.
AB  - The aim of this study was to evaluate the effects of the administration of
      pregnenolone-16alpha-carbonitrile (PCN), an inducer of the cytochrome P450 3A
      gene in rats, on vitamin E status and antioxidant enzyme protein levels in rats
      fed a vitamin E-supplemented diet. Two groups of male Wistar rats were fed for 3
      weeks with a basal diet containing 50 ppm of alpha-tocopherol or the same diet
      containing 10 times more alpha-tocopherol. In the final 3 days, each group was
      divided into two subgroups which were given a single daily intraperitoneal
      injection of PCN at 75 mg/kg (groups PCN and PCN+VE) or DMSO (groups DS and
      DS+VE). PCN treatment alone significantly reduced the alpha-tocopherol content of
      the liver and plasma and this effect was prevented by supplementation with 10
      fold more alpha-tocopherol. alpha-Tocopherol levels in the kidneys, lung, heart,
      and testes were significantly higher in both vitamin E-supplemented groups than
      in the control groups. TBARS levels in the liver and lung were significantly
      increased in both PCN-treated groups, as shown by two-way ANOVA analysis. PCN
      also caused a significant reduction in protein levels of catalase and glutathione
      peroxidase (GPx) in both groups. Dietary vitamin E supplementation caused a
      decrease in liver protein levels of GPx and superoxide dismutase, but not
      catalase, in both groups and protected against PCN-induced lipid peroxidation,
      which was caused by CYP3A induction and a reduction in antioxidant enzyme levels.

PMID- 19389274
TI  - Enzyme antioxidant defences and oxidative damage in red blood cells of variegate
      porphyria patients.
AB  - Variegate porphyria is the result of decreased protoporphyrinogen oxidase (PPOX)
      activity, the penultimate enzyme of haem biosynthesis. Haem precursors can
      produce free radicals and activate oxygen-inducing oxidative stress. Our aim was
      to analyse the effects of variegate porphyria on haemoglobin levels, antioxidant
      enzyme activities and oxidative damage in circulating erythrocytes. Twelve women
      affected by variegate porphyria and 12 control healthy women participated in the
      study. Women affected by variegate porphyria presented reduced PPOX content and
      delta-aminolevulinic acid dehydratase activity in erythrocytes. Haemoglobin
      content and mean corpuscular volume were higher in the porphyric group.
      Erythrocyte glutathione reductase and superoxide dismutase activities and
      catalase content were higher in porphyric women, although MDA levels were also
      higher in the erythrocytes of the porphyric group. In conclusion, the
      determination of PPOX could be a useful method to detect variegate porphyria.
      Despite having higher antioxidant defences, erythrocytes of porphyric women have
      greater oxidative damage and higher corpuscular volume, which are both indices of
      a situation of higher oxidative stress.

PMID- 19389275
TI  - Protective effect of thioredoxin perfusion but not inhalation in warm ischemic
      reperfused rat lungs.
AB  - BACKGROUND: Thioredoxin is a ubiquitous protein with anti-oxidative, anti
      apoptotic, and anti-inflammatory effects. It was reported [Fukuse T, Hirata T,
      Yokomise H et al. Attenuation of ischaemia reperfusion injury by human
      thioredoxin. Thorax 1995; 50: 387-391] that rhTRX protected lungs from ischemia
      reperfusion injury as a radical scavenger; however, the mechanism was not
      elucidated. Therefore, we investigated the effect of perfusion and inhalation of
      rhTRX, and the associated mechanisms, by analyzing the concentrations and
      molecular states of the perfused rhTRX. MATERIALS AND METHODS: Perfusion and
      inhalation studies of rhTRX were conducted with an isolated rat-lung perfusion
      model. The heart-lung block was perfused for 15 min and subsequently exposed to a
      55-min ischemia followed by a 120-min reperfusion. Pulmonary artery pressure,
      weight gain, dynamic airway resistance, pulmonary compliance, and tidal volume
      were measured continuously. The concentrations and molecular states of the
      perfused rhTRX were measured. RESULTS: A 350-microg/ml perfusion of rhTRX
      decreased post-ischemic pulmonary artery pressure (P < 0.05), while a 200
      microg/ml perfusion did not. Throughout the experiment, the rhTRX concentrations
      were constant, and the rhTRX molecules were mostly dimeric. The inhalation of
      rhTRX showed adverse effects on the pulmonary function compared with the control
      group (P < 0.05). CONCLUSIONS: A 350-microg/ml perfusion, but not inhalation, of
      rhTRX protected rat lungs from ischemia-reperfusion injury. rhTRX was effective
      in dimeric form without transit to the lung tissue. rhTRX may be effective by
      some mechanism other than radical scavenging.

PMID- 19389276
TI  - Hydroxyl radical oxidation of guanosine 5'-triphosphate (GTP): requirement for a
      GTP-Cu(II) complex.
AB  - Levels of oxidized guanosine base in DNA have become a hallmark biomarker in
      assessing oxidative stress implicated in a variety of disease and toxin-induced
      states. However, there is evidence that the guanosine in the nucleotide
      triphosphate pool (GTP) is more susceptible to oxidation than guanosine residues
      incorporated into nucleic acids and this causes a substantial amount of the
      oxidized product, 8-oxoguanosine 5'-triphosphate (oxo(8)GTP), to accumulate in
      cell-free and in cell-culture preparations. Electron paramagnetic resonance (EPR)
      spectroscopy and direct EPR analysis of free radical production by copper sulfate
      and L-ascorbic acid demonstrates that the hydroxyl radical (HO(*)) is produced
      via oxidation of Cu(+) to Cu(2+) while in a complex with GTP. This HO(*)
      production is dependent on the availability of oxygen and the presence of GTP in
      the reaction milieu. Verification of free radical-mediated production of
      oxo(8)GTP is presented using HPLC with electrochemical detection and matrix
      assisted laser desorption/ionization linear time-of-flight mass spectrometry
      (MALDI-LTOF-MS). The sum of these results is presented in a novel mechanism of
      GTP oxidation by Cu(2+) and L-ascorbic acid. A better understanding of the
      chemistry involved in this oxidative modification of GTP facilitates a more
      comprehensive understanding of its potential physiological consequences.

PMID- 19389277
TI  - Transgenic insecticidal crops and natural enemies: a detailed review of
      laboratory studies.
AB  - This review uses a data-driven, quantitative method to summarize the published,
      peer-reviewed literature about the impact of genetically modified (GM) plants on
      arthropod natural enemies in laboratory experiments. The method is similar to
      meta-analysis, and, in contrast to a simple author-vote counting method used by
      several earlier reviews, gives an objective, data-driven summary of existing
      knowledge about these effects. Significantly more non-neutral responses were
      observed than expected at random in 75% of the comparisons of natural enemy
      groups and response classes. These observations indicate that Cry toxins and
      proteinase inhibitors often have non-neutral effects on natural enemies. This
      synthesis identifies a continued bias toward studies on a few predator species,
      especially the green lacewing, Chrysoperla carnea Stephens, which may be more
      sensitive to GM insecticidal plants (16.8% of the quantified parameter responses
      were significantly negative) than predators in general (10.9% significantly
      negative effects without C. carnea). Parasitoids were more susceptible than
      predators to the effects of both Cry toxins and proteinase inhibitors, with fewer
      positive effects (18.0%, significant and nonsignificant positive effects
      combined) than negative ones (66.1%, significant and nonsignificant negative
      effects combined). GM plants can have a positive effect on natural enemies (4.8%
      of responses were significantly positive), although significant negative (21.2%)
      effects were more common. Although there are data on 48 natural enemy species,
      the database is still far from adequate to predict the effect of a Bt toxin or
      proteinase inhibitor on natural enemies.

PMID- 19389278
TI  - Effect of weather on Ips typographus (Coleoptera Curculionidae) phenology,
      voltinism, and associated spruce mortality in the southeastern Alps.
AB  - Summer drought associated with high temperatures recorded in the last few years
      has given rise to outbreaks of bark beetles developing in weakened host trees.
      The aim of this study was to investigate the possible weather effect on the
      biology of and damage caused by Ips typographus L. in the southeastern Alps. The
      study was carried out recording temperature (1962-2007), precipitation (1922
      2007), and the damage caused by I. typographus (1993-2007). In addition, data
      from pheromone-baited traps (1996-2005) provided information on the main periods
      of flight activity of I. typographus. From 1922 to 2007, precipitation during
      March-July has decreased approximately 200 mm (-22%), whereas since 1962-2007,
      mean temperatures during March-July increased approximately 2 degrees C (+13%).
      Damage caused by I. typographus was inversely correlated with March-July
      precipitation from the previous year but not correlated with temperature.
      Increases in spring temperature did not affect the development timing of the
      first generation, but only changed its onset. Earlier swarming of both
      overwintering beetles and first-generation offspring ( approximately 20 d sooner
      over 10 yr), and the early start of the second generation permitted more complete
      development of the second brood. Voltinism in this species is discussed in
      relation to thermal and photoperiodic thresholds, indicating that the occurrence
      of a third generation is limited by the summer photoperiod rather than by
      temperature. In conclusion, results suggest that spring drought increases damage
      caused by I. typographus in the following year, whereas warmer spring affects
      insect phenology.

PMID- 19389279
TI  - Ant community structure in citrus orchards in the mediterranean basin:
      impoverishment as a consequence of habitat homogeneity.
AB  - This study analyzes the structure and composition of ant communities in citrus
      orchards in Catalonia (northeast Spain) and compares them with the ant fauna
      found in natural communities of the region. In the citrus orchards considered in
      this study, the most abundant species were Lasius niger and Pheidole pallidula,
      which are behaviorally dominant species. Two other dominant species, Linepithema
      humile and Tetramorium caespitum, were also abundant, although only in one
      orchard. Species richness and diversity in the studied orchards were low compared
      with natural communities: although in orchards, there were few species and low
      diversity values, in natural communities, the number of species was higher and
      diversity also increased. This reduction of species richness and diversity was
      not modified by edge effects: only light and local differences were found between
      the inner part of the orchards and the orchard margins, and differences among
      orchards were greater than differences between inner parts and edges. The
      activity peaks of the different ant species actively foraging on these citrus
      orchards were distributed throughout the whole activity period of ants. Overall,
      the composition of ant communities present in the citrus orchards of this study
      was extremely poor. This agrees with the fact that monocultures are ecosystems
      associated with an inevitable loss of biodiversity and abundance of insect
      populations.

PMID- 19389280
TI  - Consequences of prescribed fire and grazing on grassland ant communities.
AB  - Prescribed fire and livestock grazing are used for the management and restoration
      of native grasslands the world over; however, the effects of these management
      techniques on ant communities are unclear. We examined the response of ants to
      these disturbances in grasslands in northern California. Twenty-four 30 by 30 m
      plots were established across two sites that received one of four treatments:
      grazing, fire, grazing and fire, or no treatment. Ants were censused using 240
      pitfall traps with one preburn and two postburn samples (14 d and 1 yr after
      burning). We analyzed ant abundance using broadly defined groups based on feeding
      habit and/or habitat use and detected no grazing effect but a significant fire
      effect that differed by group. Immediate postfire sampling showed an increase in
      cryptic species (particularly Brachymyrmex depilis). One year after the fire, no
      response was detected for cryptic species, but burned plots had greater abundance
      of seed harvesters. Analysis of vegetation showed burned plots had significantly
      greater forb cover, which might have provided greater food resources, and also
      lower biomass, which might have facilitated foraging. Understanding the effects
      of these management tools on ant abundance complements our understanding of their
      effect on vegetation and assists conservation practitioners effectively manage
      grassland ecosystems both in California and beyond.

PMID- 19389281
TI  - Population abundance of Frankliniella occidentalis (Thysanoptera: Thripidae) and
      natural enemies on plant hosts in central Chile.
AB  - Populations of the invasive Frankliniella occidentalis (Pergande) are serious
      pests of agricultural crops in the Aconcagua Valley of central Chile. An
      extensive survey was conducted of 55 plant species in 24 families to identify
      plant hosts of F. occidentalis and to determine its relative abundance on each
      host during each season. A more intensive study was conducted on selected plant
      species serving as reproductive hosts to determine the population dynamics of F.
      occidentalis and to evaluate the potential importance of Orius species and other
      natural enemies for controlling F. occidentalis. Adults of F. occidentalis were
      active during each season of the year inhabiting the flowers of 91% of the
      sampled plant species in 22 families, and 86% of these plant species in 19
      families served as reproductive hosts. The number of host plant species used was
      greatest in the spring and least in the winter. All of the hosts except Medicago
      sativa L. were used only when flowering. Populations of F. occidentalis were
      significantly aggregated in M. sativa in the terminal buds over the leaves when
      the host was not flowering, and in the flowers, followed by the terminal buds,
      followed by the leaves when the host was flowering. Larvae were 1.3-2.3 times
      more abundant on dates when M. sativa was flowering. There were no identifiable
      patterns in plant hosts based on endemicity or plant family. Most of the plant
      species used by F. occidentalis were inferior quality hosts where populations
      either declined or were stable. Populations of F. occidentalis on low-quality
      hosts generally escaped predation by Orius species and competition by other
      species of thrips. Only 25% of the food hosts and 28% of the reproductive hosts
      for F. occidentalis in the extensive survey, respectively, were host plants for
      Orius. Parasitoids and other predators were not found to be important in
      suppressing thrips on any of the plant hosts. Populations of F. occidentalis
      increased on only a few hosts, including M. sativa and Sisymbrium officinale L.
      Scop. These apparently are major sources of F. occidentalis adults invading
      crops. We conclude that F. occidentalis is established in central Chile and that
      it has replaced and possibly displaced the native Frankliniella australis
      (Morgan) as the most common thrips species.

PMID- 19389282
TI  - Transmission of insect-vectored pathogens: effects of vector fitness as a
      function of infectivity status.
AB  - The transmission of insect-vectored pathogens is dependent on the population
      dynamics of the vector. Epidemiological models typically assume that birth and
      death rates of pathogen-free and inoculative vectors are equal, an assumption
      that is not true for all pathosystems. Here, a series of simple and general
      epidemiological models were used to explore how assumptions about birth and death
      rates of vectors based on their infectivity status influence disease incidence.
      With fixed death rate of pathogen-free vectors, increasing the death rate of
      inoculative vectors reduced vector density, the proportion of vectors that were
      inoculative, and the proportion of hosts infected. This effect was mediated by
      acquisition rate. Specifically, increasing the acquisition rate increased the
      proportion of vectors that were inoculative, thereby increasing the proportion of
      the vector population that experienced the increased death rate. With fixed birth
      rate of pathogen-free vectors, variation in birth rate of inoculative vectors had
      little influence on disease incidence provided that the birth rate of pathogen
      free vectors was much greater than their death rate. However, when the birth rate
      of pathogen-free vectors was only slightly greater than their death rate, large
      increases in the birth rate of inoculative vectors increased total vector density
      and disease incidence. The results indicate that assumptions about birth and
      death rates of vectors based on infectivity status can have important effects on
      the vector population that in turn affects disease incidence.

PMID- 19389283
TI  - Insect associates of Ceratocystis albifundus and patterns of association in a
      native savanna ecosystem in South Africa.
AB  - Species of Ceratocystis Ellis and Halstead s.l. include important plant pathogens
      such as C. albifundus Morris, De Beer, and M. J. Wingfield that causes a serious
      wilt disease of non-native, plantation-grown Acacia mearnsii De Wild. trees in
      Africa. The aim of this study was to identify the insects associated with C.
      albifundus in South Africa and to consider the means by which the pathogen
      spreads. Insects were collected weekly for 77 wk in a native ecosystem using
      modified pitfall traps. Trapped insects were identified, and fungi were isolated
      using carrot baiting and by plating them onto malt extract agar. Fungi were
      identified using morphological characteristics and DNA sequence comparisons.
      Three different nitidulid (Coleoptera: Nitidulidae) beetles, Brachypeplus
      depressus Erichson, Carpophilus bisignatus Boheman, and Ca. hemipterus L, were
      collected, of which the most common were the Carpophilus spp. Two Ceratocystis
      spp., namely C. albifundus and C. oblonga R. N. Heath and Jolanda Roux, were
      isolated from all three insect species. Insect numbers and fungal isolates
      decreased significantly in the colder months of the year. Of the two Ceratocystis
      spp., C. oblonga was most abundant, occurring on 0.5% of the Carpophilus spp. C.
      albifundus was isolated from 1.1% of the Brachypeplus individuals and from 0.01%
      of the Carpophilus individuals. This study presents the first record of insects
      associated with C. albifundus and C. oblonga and provides an indication of
      environmental influences on fungal and insect populations, which could contribute
      to future disease management.

PMID- 19389284
TI  - Spatial patterns of parasitism of the solitary parasitoid Pseudapanteles dignus
      (Hymenoptera: Braconidae) on Tuta absoluta (Lepidoptera: Gelechiidae).
AB  - We examined the interaction between the tomato leafminer, Tuta absoluta (Meyrick)
      (Lepidoptera: Gelechiidae), a key pest of tomato crops in South America, and its
      main solitary larval parasitoid, Pseudapanteles dignus (Muesebeck) (Hymenoptera:
      Braconidae). The pattern of parasitism of T. absoluta by the parasitoid was
      studied at three scales on tomato crops: plant, leaf, and leaflet. Host density,
      spatial distributions of both host and parasitoid, percentages of parasitism,
      variation in the probability and risk of parasitism in relation to host density,
      and the spatial density dependence were assessed in a horticultural region in
      Argentina. The spatial distribution of T. absoluta was clumped at all sites and
      scales, whereas that of P. dignus was much more variable, fitting to negative,
      positive binomial distributions and to Poisson series. Percentages of parasitism
      were as follows: site 1, 17.06%; site 2, 27.53%; site 3, 26.47%; site 4, 45.95%.
      Parasitoid aggregation in relation to host density was found at leaf and leaflet
      scales. However, the proportion of parasitized hosts was independent of host
      density. The variability of parasitism rates exhibited at the three spatial
      scales seems to result in partial refuges for the host, which might contribute to
      the persistence of the interaction between host and parasitoid. We discuss our
      field observations in relation to ecological theory and its potential application
      to the biological control of T. absoluta on tomato.

PMID- 19389285
TI  - Survey of stink bug (Hemiptera: Pentatomidae) egg parasitoids in wheat, soybean,
      and vegetable crops in southeast Virginia.
AB  - Stink bugs (Hemiptera: Pentatomidae) cause significant damage to many different
      crops and horticultural commodities in Virginia. However, little is known about
      the species diversity or impact of stink bug egg parasitoids in the state. A
      survey was conducted in 2005 and 2006 (May through September) in wheat (Triticum
      aestivum L.), soybean (Glycine max L.), and several vegetable crops by collecting
      natural egg masses of various stink bug species and by monitoring sentinel egg
      masses. A total of 570 Euschistus servus (Say) eggs in 26 egg masses, 11,197
      Murgantia histrionica (Hahn) eggs in 939 egg masses, 15 Podisus maculiventris
      (Say) eggs in 2 egg masses, and 546 Acrosternum hilare (Say) eggs in 18 egg
      masses were field collected and returned to the laboratory, where emerging
      parasitoids were identified to species. In addition, 2,512 laboratory-reared E.
      servus eggs and 230 P. maculiventris eggs were placed as sentinels into crop
      fields and collected after 7 d, and parasitoid or stink bug emergence was
      recorded. Four species of hymenopteran parasitoids in the family Scelionidae were
      recovered from stink bug eggs: Telenomus podisi Ashmead, Trissolcus basalis
      Wollaston, Trissolcus edessae Fouts, and Trissolcus euschisti Ashmead. In
      addition, one parasitoid in the family Mymaridae (Hymenoptera) was recovered.
      Parasitism rates were highest in E. servus with 89.7 and 49.2% of egg masses and
      individual eggs parasitized, respectively. The predominant parasitoid species was
      T. podisi.

PMID- 19389286
TI  - Abundance of Icerya purchasi (Hemiptera: Margarodidae) and its parasitoid
      Cryptochaetum iceryae (Diptera: Cryptochaetidae) in Argentina blueberry crops.
AB  - Icerya purchasi Maskell is a polyphagous scale pest of ornamentals and several
      other crops. It has two natural specialist enemies that maintain its populations
      at low levels: Rodolia cardinalis (Mulsant) and Cryptochaetum iceryae
      (Williston). I. purchasi was recently observed in blueberry crops (Vaccinium
      corymbosum L.) in Argentina. Seven blueberry fields located in different
      agricultural landscapes were sampled from July 2006 to September 2008. I.
      purchasi was present only in the citrus areas of Gobernador Castro, San Pedro,
      and Concordia. In the last locality, it was present in January 2007, and the
      abundance was very low. In Buenos Aires, I. purchasi was more abundant in
      Gobernador Castro where it was present throughout all study period. In San Pedro,
      it was only registered in August 2007 and March, April, and June 2008. In
      Gobernador Castro, where the abundance was highest, the dominant crop near
      blueberries is citrus. The low abundance in San Pedro and Concordia fields may be
      attributable to the replacement of citrus crops by nonhosts. In Concordia and San
      Pedro fields, no parasitized I. purchasi were found. In Gobernador Castro, the
      proportion of adults parasitized was 0.805 +/- 0.286. When the risk of parasitism
      was analyzed for three density categories, there were no significant differences.
      R. cardinalis was present only in Gobernador Castro, and very few individuals
      were observed. The presence and abundance of I. purchasi in blueberry crops in
      Argentina seems to be linked to the structure of the landscape at the regional
      level, and the variable incidence of C. iceryae suggests major constraints to the
      scale's population growth.

PMID- 19389287
TI  - Mycoses of wheat stem sawfly (Hymenoptera: Cephidae) larvae by Fusarium spp.
      isolates.
AB  - A complex of Fusarium spp., including F. pseudograminearum, F. culmorum, F.
      avenaceum, F. equiseti, and F. acuminatum, was isolated from field-collected
      larval cadavers of wheat stem sawfly at two locations for 2 yr. The Fusarium spp.
      isolates caused mortality in both diapausing larvae in a topical bioassay and in
      developing larvae feeding in infected stems in a greenhouse experiment. Larval
      mortality was >90% in both experiments at the highest dose. The pattern of
      correlation between integument discoloration, hyphal growth, and larval mortality
      showed that the Fusarium spp. isolates actively infect larvae and kill them,
      rather than colonizing larval tissue as secondary postmortem invaders. The
      versatility of Fusarium spp. as plant and insect pathogens enables colonization
      that results in disease in wheat plants and subsequent mortality of the wheat
      stem sawfly larvae developing within the same tissue.

PMID- 19389289
TI  - A mechanical plant defense defines the opening of a phenological window for gall
      induction by Asphondylia aucubae (Cecidomyiidae: Diptera).
AB  - Many insect herbivores can only use hosts during a specific phenological stage,
      i.e., a phenological window. Previous studies have primarily examined the effects
      of these windows on insect herbivores, but relatively little is known about the
      mechanisms controlling the phenological windows. In most gall insect systems,
      phenological windows have been attributed to the short duration of
      physiologically active plant tissues that induce gall formation (reactive plant
      tissue). In the fruit gall midge, Asphondylia aucubae Yukawa and Ohsaki, and the
      host plant (i.e., Aucuba japonica) system, the disappearance of reactive plant
      tissue closes the phenological window, but its presence does not define the
      opening of the window. The hard endocarp of the fruit covers most potential
      oviposition sites just before the midge emergence season, but decreases in
      proportional cover during the emergence season. We experimentally manipulated the
      timing of oviposition relative to fruit development. Midges that emerged earliest
      and attacked fruits during their earliest developmental stages were unable to
      oviposit because of intact, hard endocarps, whereas their counterparts that
      emerged later could oviposit more readily through cracks in the endocarp. We
      noted possible oviposition avoidance behavior and the necessity of more frequent
      (repeated) ovipositor insertions to intensively stimulate the decreased reactive
      tissues during the latter half of the emergence season. Overall, our results
      indicated that the fragmentation of the defensive, hard endocarp of the host
      plant defines the opening of the phenological window in this plant-herbivore
      system.

PMID- 19389288
TI  - Insect frass as a pathway for transmission of bacterial wilt of cucurbits.
AB  - Insects that vector diseases of plants are of critical concern to agriculture,
      but relationships between the vectors and pathogens often are poorly understood.
      In this study, we present research on vector relationships between the striped
      cucumber beetle, Acalymma vittatum (F.) (Coleoptera: Chrysomelidae), and the
      pathogen that causes bacterial wilt of cucurbits, Erwinia tracheiphila (Smith)
      (Enterobacteriales: Enterobacteriaceae). We studied how the bacteria were
      retained in the gut of the beetle by developing a polymerase chain reaction (PCR)
      based technique for extracting and identifying bacterial DNA in the frass.
      Bacterial DNA usually was present in the frass for 24 h after beetles had
      consumed inoculum but diminished quickly and was undetectable within 96 h. The
      amount of time that bacterial DNA could be detected in frass increased with the
      amount of inoculum and the length of time that beetles were exposed to inoculum
      and also varied with the strain of bacterium. Frass that tested positive for
      bacterial DNA also was infective to cucumber plants, confirming that DNA was
      indicative of viable bacteria and that frass could be a pathway for transmission
      of the pathogen. This research suggests that few cucumber beetles serve as long
      term vectors of the pathogen and that aggregation of the beetle on host plants
      may be critical for initiating plant infections in spring.

PMID- 19389290
TI  - Chlorotic feeding injury by the black pecan aphid (hemiptera: aphididae) to pecan
      foliage promotes aphid settling and nymphal development.
AB  - The nature of the interaction between the black pecan aphid, Melanocallis
      caryaefoliae (Davis) (Hemiptera: Aphididae), and the chlorosis it causes to
      foliage of its pecan [Carya illinoinensis (Wangenh.) K. Koch)] host is poorly
      understood. Laboratory experiments were conducted on the settling behavior of the
      black pecan aphid, when provided chlorotic pecan leaf discs resulting from
      previous black pecan aphid feeding and nonchlorotic leaf discs, under a normal
      photoperiod and constant dark. Additionally, aphid development from the first
      instar to the adult stage was examined when nymphs were either allowed to feed on
      the same leaf disc or moved daily to a new, nondamaged, same age leaf disc. After
      24 h, a significantly higher percentage of black pecan aphids settled on
      chlorotic than on nonchlorotic leaf discs, regardless of photoperiod. When
      starting from the first instar, nymphs that were prevented from inducing leaf
      chlorosis by moving daily to new, same-age leaf discs took approximately 5 d
      longer to complete development, had a shorter body length, and had higher
      mortality than when aphids remained on the same leaf disc. These results show
      that black pecan aphid-induced leaf chlorosis plays an important role in the
      interaction of the black pecan aphid with its pecan host.

PMID- 19389291
TI  - Woody stem galls interact with foliage to affect community associations.
AB  - Gall wasps (Hymenoptera: Cynipidae) hijack the physiology of their host plant to
      produce galls that house wasps throughout their immature stages. The gall-maker
      host plant interaction is highly evolved, and galls represent an extended
      phenotype of the gall wasp. We evaluated two-way interactions between stem galls
      produced by Dryocosmus kuriphilus Yasumatsu on Castanea spp. (Fagales: Fagaceae)
      and foliage directly attached to galls (gall leaves) using gall leaf excision
      experiments and herbivore bioassays. Early season gall leaf excision decreased
      the dry weight per chamber (nutritive index) and thickness of the protective
      schlerenchyma layer and increased the number of empty chambers and the occurrence
      and size of exterior fungal lesions. Leaf excision also caused a modestly
      significant (alpha = 0.1) increase in the incidence of feeding chamber fungi and
      herbivory by Curculio sayi Gyllenhal (Coleoptera: Curculionidae), and a modest
      decrease in parasitoids. This study shows that gall leaves are important for stem
      gall development, quality, and defenses, adding support for the nutrient and
      enemy hypotheses. We also evaluated the effects of stem galls on the suitability
      of gall leaves to Lymantria dispar L. (Lepidoptera: Lymantriidae) herbivory to
      assess the extent of gall defenses in important source leaves. Relative growth
      rate of L. dispar larvae was greater on gall leaves compared with normal leaves,
      indicating that, despite their importance, gall leaves may be more suitable to
      generalist insect herbivores, suggesting limitations to the extended phenotype of
      the gall wasp. Our results improve our knowledge of host-cynipid interactions,
      gall source-sink relations, and D. kuriphilus community interactions.

PMID- 19389292
TI  - Male Megacyllene robiniae (Coleoptera: Cerambycidae) use multiple tactics when
      aggressively competing for mates.
AB  - Adult male Megacyllene robiniae (Forster) (Coleoptera: Cerambycidae) that are
      paired with a female often are challenged by conspecific males that attempt to
      displace them. In staged laboratory bouts, challenging males used seven distinct
      tactics to displace defending males, including wedging their head between the
      defender and the female (termed wedging), straddling the mated pair and pulling
      the defender off (prying), pulling it with the mandibles, batting it with the
      antennae, or pushing, biting, or kicking the defender. Individual challengers
      attempted as many as six different tactics in a single bout, repeating certain
      tactics multiple times. They often attempted tactics that were not very
      effective. For example, prying was one of the most common attempted tactics but
      was rarely effective. However, few challengers attempted to push defenders off
      the female, even though that tactic often was effective. Challengers apparently
      were influenced by context in their choice of particular tactics. For example,
      males that approached the mated pair from the side were likely to use wedging,
      whereas those approaching head on were more likely to bat with the antennae.
      Choice of tactic apparently was not influenced by absolute size of challengers,
      nor was it strongly influenced by relative size of defenders. However, the
      effectiveness of tactics varied significantly with relative body size: larger
      challengers were most successful when prying or pushing, while smaller
      challengers were most successful when biting and kicking. By using different
      tactics, relatively small males were as adept as larger males at displacing
      rivals.

PMID- 19389293
TI  - Edge effects in the directionally biased distribution of Choristoneura rosaceana
      (Lepidoptera: Tortricidae) in apple orchards.
AB  - Edge effect tests have been used in a number of studies on obliquebanded
      leafroller, Choristoneura rosaceana (Harris), to test for evidence of mated
      female immigration into pheromone-treated orchards. This type of test compares
      obliquebanded leafroller presence or activity around the perimeter of an orchard
      against presence or activity in the interior. Higher numbers detected around the
      edges of an orchard would indicate higher levels of flight activity at the edge,
      a pattern that could be generated by high levels of immigration. Recent work has
      shown that the spatial distribution of recaptured obliquebanded leafroller adults
      released from a single location can be directionally biased, which could obscure
      the ability to detect an edge effect. To test this theory, data from an orchard
      study conducted in 1991 that found no significant edge effect was reanalyzed.
      When we accounted for the directional bias in the distribution of first
      generation mated female moths, we found an edge effect with significantly more
      mated females captured in the edge traps than in the center or mid-interior
      traps. No edge effect was found when the directional bias was ignored. In
      addition, second-generation males and mated females both showed a significant
      edge effect that had not been detected in the original analysis, which had
      combined both first- and second-generation data.

PMID- 19389294
TI  - Influence of cover crop and intercrop systems on Bemisia argentifolli (Hemiptera:
      Aleyrodidae) infestation and associated squash silverleaf disorder in zucchini.
AB  - Field experiments were conducted to evaluate the effects of cover cropping and
      intercropping on population densities of silverleaf whitefly, Bemisia
      argentifolli Bellow and Perring, and the incidence of squash silverleaf disorder
      (SSL) in zucchini, Cucurbita pepo L., in Oahu, HI. Two cover crops, buckwheat
      (BW), Fagopyrum esculentum Moench, and white clover (WC), Trifolium repens L., or
      sunn hemp (SH), Crotolaria juncea L., and an intercropped vegetable, okra,
      Abelmonchus esculentus L., were evaluated during the 2003, 2005, and 2006 growing
      seasons, respectively. Population densities of whiteflies and SSL severity varied
      during the three field experiments. In 2003, the severity of SSL and percentage
      of leaves displaying symptoms were significantly lower on zucchini plants in WC
      than BW plots throughout the crops' growth cycle. Additionally, the percentage of
      leaves per plant displaying SSL symptoms was significantly greater in bare-ground
      (BG) compared with the pooled BW and WC treatments on each inspection date. In
      2005, zucchini intercropped with okra had lower numbers of adult whiteflies and
      resulted in significantly lower severity of SSL than pooled BW and WC treatments.
      During 2006, zucchini grown with SH had significantly lower numbers of all
      whitefly stages (i.e., egg, immature, and adult) and less SSL severity symptoms
      than BW. Despite these differences in whitefly numbers and SSL severity,
      marketable yields were not significantly lower in BW compared with WC or SH
      treatment plots during the study. The mechanisms underlying these results and the
      feasibility of using cover crops and intercrops to manage B. argentifolli and SSL
      are discussed.

PMID- 19389295
TI  - Early-season soybean as a trap crop for stink bugs (Heteroptera: Pentatomidae) in
      Arkansas' changing system of soybean production.
AB  - Early-season soybean, Glycine max L. Merrill, was evaluated in Arkansas soybean
      fields as a trap crop for a complex of stink bug species that included Nezara
      viridula L., Acrosternum hilare (Say), and Euschistus servus (Say). Early-season
      soybean production systems (ESPSs) are composed of indeterminate soybean
      cultivars planted in April. In the first year of a 2-yr study, field-scale trap
      crops ( approximately 0.5-1.0 ha) of maturity group (MG) III and IV soybean were
      planted adjacent to production fields of MG V soybean. Stink bugs were attracted
      first to the ESPS trap crops and were twice treated with insecticide, yet
      damaging populations developed later in the MG V soybean adjacent to the trap
      crops. General sampling and observations of low stink bug densities in commercial
      fields of soybean and corn across the study area suggested that stink bugs were
      widely distributed across the agricultural landscape. These observations and the
      subsequent discovery of additional ESPS fields outside the study area suggested
      that developing populations in the adjacent MG V soybean probably did not
      originate from the trap crops. However the source of the populations colonizing
      MG V soybean could not be determined, and we concluded that the scale of future
      experiments should be increased to better control stink bugs dispersing from
      other ESPSs outside the study area. In the second year of the study, the
      experiment was expanded in size to a farm- or community-scale project where
      entire fields of ESPSs (8-32 ha) were used as trap crops. Insecticide was applied
      to the trap-crop fields and other fields of ESPSs within a 0.8-km radius of
      targeted response fields, yet again there was no apparent effect on subsequent
      populations of stink bugs in the MG V response fields. With the recent expansion
      of ESPSs in Arkansas, it may be difficult to use ESPSs as a trap crop to lower
      stink bug populations across large enough areas to suppress populations in late
      season soybean. Also, multiple soybean cultivars are generally planted across a 2
      or 3-mo period in Arkansas, which results in staggered soybean development
      across the landscape and extends the time period that soybean is attractive to
      colonizing stink bugs. Trap crops of ESPSs are only attractive for oviposition
      for up to 4-5 wk and cannot protect full-season soybean production systems
      (FSSPSs) for such an extended time period. This shift in production systems may
      limit the use of ESPS trap crops for management of stink bugs unless highly
      coordinated efforts are made to synchronize soybean maturity and control stink
      bugs in ESPSs across large geographic areas.

PMID- 19389296
TI  - Development of a combined sex pheromone-based monitoring system for Malacosoma
      disstria (Lepidoptera: Lasoicampidae) and Choristoneura conflictana (Lepidoptera:
      Tortricidae).
AB  - Sympatric insect species that do not share sex pheromone components but have a
      common host and overlapping adult flight periods are potential targets for the
      development of a combined sex pheromone-based monitoring tool. A system using a
      single synthetic pheromone blend in a single lure to bait a single trap to
      monitor two pests simultaneously represents a novel approach. In this study, a
      combined pheromone-based monitoring system was developed for two lepidopterous
      defoliators of trembling aspen Populus tremuloides Michenaux in western Canada,
      Malacosoma disstria Hubner (Lepidoptera: Lasoicampidae) and Choristoneura
      conflictana (Walker) (Lepidoptera: Tortricidae). Efficacy and longevity of a lure
      containing both species' pheromones were tested. Immature stages of each species
      were sampled to evaluate the ability of pheromone traps baited with the combined
      lure to predict population density. The combined lure was as attractive to M.
      disstria and C. conflictana males as were traps baited with each species'
      pheromone alone. Lure age had no effect on attraction of male C. conflictana to
      the combined lure but had a negative effect on attraction of M. disstria. The
      number of male moths captured in traps baited with the combined lure was related
      to immature counts for both species. Pupal counts of M. disstria and larval
      counts of C. conflictana provided the best relationships with male captures. The
      combined lure does not attract M. disstria males in direct proportion to
      population density, because trap catch was comparatively low at high-density M.
      disstria sites.

PMID- 19389297
TI  - Electrophysiological and behavioral responses of Dendroctonus valens (Coleoptera:
      Curculionidae: Scolytinae) to four bark beetle pheromones.
AB  - The red turpentine beetle, Dendroctonus valens LeConte (Coleoptera:
      Curculionidae: Scolytinae), has caused extensive mortality of Pinus tabuliformis
      Carriere in north central China. The electrophysiological and behavioral
      activities of the four bark beetle pheromones, frontalin, exo-brevicomin, trans
      verbenol, and cis-verbenol, singly or in combination with host-produced
      kairomones, were tested on red turpentine beetles. Both sexes showed a consistent
      electrophysiological response to the four test compounds. In Y-tube olfactometer
      bioassays, walking red turpentine beetles selected the host compound (+)-3-carene
      over any of the test compounds, but significantly higher numbers chose each
      tested pheromone over a blank control. The four compounds, tested singly or in
      combination, were not attractive to red turpentine beetles in field trapping
      studies in 2006 and 2007 and also did not significantly increase trap catch when
      combined with (+)-3-carene. Frontalin, alone or in combination with exo
      brevicomin and trans-verbenol, significantly reduced the attractiveness of (+)-3
      carene in 2006 but not in 2007. The possible roles of the pheromones in host and
      mate finding and selection are discussed.

PMID- 19389298
TI  - Development of the powderpost beetle (coleoptera: bostrichidae) at constant
      temperatures.
AB  - Development of Dinoderus minutus was studied under laboratory conditions at five
      constant temperatures (15, 18, 25, 28, and 30 degrees C) to estimate
      developmental thresholds and thermal requirements of the egg, larva, pupa, and
      egg-to-adult stages. Adults began to burrow along the grain into bamboo pieces
      within 24 h after cutting and continued across the grain. Female beetle
      oviposited an average of 9.1 eggs in the ensuing 24 h, all in the metaxylem. The
      average period for development of eggs, larva, and pupa were 5.4, 43.8, and 4.6 d
      at 30 degrees C, respectively. The development rate data were regressed through
      the x-axis to derive the thermal constants of 4.3, 6.8, and 4.5 degrees C and
      thermal requirements of 113.6, 909.1, and 96.2 DD to predict D. minutus egg
      oviposition to hatch, larva-to-pupa development, and adult emergence from pupa,
      respectively. The thermal threshold for egg-to-adult development was 6.4 degrees
      C, with total thermal requirements of 1,111.1 DD. Oviposition, emergence, and
      thermal requirements for development of the various stages of D. minutus may be
      used for postharvest pest management of bamboo.

PMID- 19389299
TI  - Nest site selection influences mortality and stress responses in developmental
      stages of Megachile apicalis Spinola (Hymenoptera: Megachilidae).
AB  - We examined stress responses and survival in developmental stages of the invasive
      solitary bee Megachile apicalis Spinola during two nesting seasons in the Central
      Valley of California to consider whether abiotic stress tolerance of its
      offspring contributes to this species' successful colonization of the western
      United States. In 2001 and 2003, artificial nesting cavities were affixed to
      vertical plywood boards oriented to maximize nest cavity temperature and humidity
      differences: one side faced south (exposed to direct sun) and the other one faced
      north (shaded). After several weeks of nesting activity, we measured heat shock
      protein 70 (HSP70) concentrations in adults and offspring on 1 d in both years
      and offspring survival and mortality sources in 2003. In 2001, M. apicalis showed
      higher HSP70 concentrations in exposed nests than in shaded nests during all
      developmental stages, adults and their offspring. In 2003, overall survivorship
      was not significantly different between treatments because exposed nests
      experienced high offspring mortality caused by heat stress, whereas shaded nests
      suffered similarly high offspring mortality because of parasitoids. In both years
      of our study, females preferred shaded nests over exposed nests. M. apicalis
      successfully reproduces in grasslands of the Central Valley of California where
      offspring survive hot, dry nest sites and parasitoids in sufficient numbers to
      inoculate new grassland habitats, unpopulated by tolerance-limited native
      solitary bees, with incipient populations of this bee, M. apicalis.

PMID- 19389300
TI  - Effects of the insect growth regulator, methoprene, on Onthophagus taurus
      (Coleoptera: Scarabaeidae).
AB  - A bioassay was conducted to determine the impact of methoprene, an insect growth
      regulator (IGR), on fecundity, larval survival, and size of progeny for
      Onthophagus taurus Schreber. Adult O. taurus dung beetles were offered methoprene
      treated manure in three to five replications each at concentrations of 0.08,
      0.45, and 4.5 ppm, respectively. An additional group of adult beetles was
      immersed in a methoprene-water solution and allowed to reproduce in containers
      with untreated manure. Data from all treatment groups were compared with
      untreated control groups. Methoprene did not seem to hinder brood production at
      0.45 ppm. Survival of O. taurus was not affected by methoprene-treated manure at
      0.08 ppm or when parent beetles were immersed in methoprene-water solution.
      However, progeny survival was significantly reduced on manure treated with
      methoprene at 4.5 ppm. Mean pronotal width of O. taurus progeny was significantly
      smaller in beetles fed methoprene-treated manure (4.5 ppm). The low dose of 0.08
      ppm did not affect pronotal widths nor did topical application of methoprene to
      adults affect pronotal widths in resulting offspring. Although some adverse
      effects of methoprene were observed at higher concentrations, use of methoprene
      at concentrations of 0.08 ppm as part of a horn fly control program likely would
      not greatly affect populations of O. taurus, the most common paracoprid dung
      beetle in North Carolina.

PMID- 19389301
TI  - Selective advantage for IIIM males over YM males in cage competition, mating
      competition, and pupal emergence in Musca domestica L. (Diptera: Muscidae).
AB  - In the house fly, Musca domestica L. (Diptera: Muscidae), sex is usually
      determined by a dominant factor, M, located on the Y chromosome. However, there
      are autosomal male (A(M)) populations in which the M factor is located on one or
      more of the five autosomes (I-V), most commonly on the third chromosome. Herein
      we report the use of isogenic strains to determine the relative fitness of Y(M)
      versus III(M) males in three different experiments. First, cages were started
      with 50% Y(M) and 50% III(M) males, and the frequencies of Y(M) and III(M) males
      were evaluated across generations. Second, mating competition studies were
      preformed with these isogenic strains. Third, the relative emergence rates of
      III(M) versus Y(M) male pupae held at three temperatures for 3 d were examined.
      All three studies indicate that III(M) males have a greater fitness than Y(M)
      males. In the cage competition studies, >90% of the males were III(M) after seven
      generations. III(M) males were more likely to mate than Y(M) males, and a higher
      percent of III(M) males emerged after being held as pupae at 4, 16, or 28 degrees
      C for 3 d. The implications of these studies to the distribution of III(M) and
      Y(M) males in field populations are discussed.

PMID- 19389302
TI  - Molecular identification of Cinara cupressi and Cinara tujafilina (Hemiptera,
      Aphididae).
AB  - A condition called "cypress mortality" affects forest of Austrocedrus chilensis
      (D. Don) Pic. Ser et Bizarri in Argentina. Their classic groups of symptoms has
      been described as a slow process of defoliation that culminating in death of the
      tree; nevertheless, dying and recently dead trees with abundant foliage are
      frequently observed in which foliage changes to red. Cinara (Cupressobium)
      cupressi (Buckton) is considered the agent responsible for reddening this
      indigenous conifer in Chile. Therefore, the relationship between the presence of
      C. cupressi and the new aerial symptoms in A. chilensis from Argentina required
      evaluation. However, Cinara (Cupressobium) tujafilina (del Guercio) also has been
      reported from this host, and the differentiation of both species of Cinara is
      time consuming and requires a great expertise because they share many morphologic
      and microscopic characters. A rapid molecular method of identification of C.
      cupressi and C. tujafilina is desirable to detect and differentiate them. We
      report the development and evaluation of a polymerase chain reaction-restriction
      fragment length polymorphism method based on the mitochrondial cytochrome oxidase
      I gene to identify C. cupressi and C. tujafilina in colonies of aphids. The first
      detection of C. cupressi from A. chilensis in Argentina, is reported based on the
      new method.

PMID- 19389304
TI  - The spatial learning phenotype of heterozygous leaner mice is robust to
      systematic variation of the housing environment.
AB  - Providing stimulation and allowing the performance of motivated behaviors through
      environmental enrichment improves learning and memory in rodents and delays
      cognitive impairment in neurodegenerative disease models. The leaner mutation
      affects the Ca(v)2.1 voltage-gated calcium channel alpha(1A)-subunit gene, and
      homozygous mice show severe phenotypic alterations. Although several authors have
      described heterozygous mice as normal, recent studies in our laboratory indicate
      motor and cognitive impairment in tg(la)/+ mice. In the present study, we
      evaluated whether this impairment is robust to systematic variation of the
      housing environment from barren to standard and furnished (enriched) cages.
      Wildtype (n = 55) and tg(la)/+ (n = 79) C57Bl/6J mice were assigned randomly to 1
      of the 3 housing systems and tested on the Morris water maze at 6, 12, and 20 mo
      of age. The results confirmed impaired performance in tg(la)/+ mice, particularly
      in older mice. At 12 and 20 mo, only wildtype (and not tg(la)/+) mice showed
      evidence of learning (spending increased time in the target quadrant) during the
      probe trial. Housing also affected performance: at 12 mo, only mice from
      furnished cages showed evidence of learning, and in aged mice (20 mo), only those
      housed in more complex environments showed long-term memory (8 mo after previous
      testing) of the platform position. In conclusion, a heterozygous mutation in a
      Ca(2+) channel gene causes cognitive deficits in leaner mice that are robust to
      environmental variation but attenuated by physical and behavioral stimulation.

PMID- 19389303
TI  - Enhancing the ability of experimental autoimmune encephalomyelitis to serve as a
      more rigorous model of multiple sclerosis through refinement of the experimental
      design.
AB  - Advancing the understanding of the mechanisms involved in the pathogenesis of
      multiple sclerosis (MS) likely will lead to new and better therapeutics. Although
      important information about the disease process has been obtained from research
      on pathologic specimens, peripheral blood lymphocytes and MRI studies, the
      elucidation of detailed mechanisms has progressed largely through investigations
      using animal models of MS. In addition, animal models serve as an important tool
      for the testing of putative interventions. The most commonly studied model of MS
      is experimental autoimmune encephalomyelitis (EAE). This model can be induced in
      a variety of species and by various means, but there has been concern that the
      model may not accurately reflect the disease process, and more importantly, it
      may give rise to erroneous findings when it is used to test possible
      therapeutics. Several reasons have been given to explain the shortcomings of this
      model as a useful testing platform, but one idea provides a framework for
      improving the value of this model, and thus, it deserves careful consideration.
      In particular, the idea asserts that EAE studies are inadequately designed to
      enable appropriate evaluation of putative therapeutics. Here we discuss problem
      areas within EAE study designs and provide suggestions for their improvement.
      This paper is principally directed at investigators new to the field of EAE,
      although experienced investigators may find useful suggestions herein.

PMID- 19389305
TI  - Novel pathologic findings associated with urinary retention in a mouse model of
      mucopolysaccharidosis type IIIB.
AB  - Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome type B) is a
      metabolic disorder with devastating clinical characteristics starting in early
      childhood and leading to premature death. A knockout mouse strain was developed
      that models this disease. Mice of the strain B6.129S6- Naglu(tm1Efn)/J are
      invaluable for investigating pathogenesis and possible treatment modalities.
      However, the mouse strain also exhibits some objectionable phenotypic features.
      One such feature, urinary retention, not only is atypical of human MPS IIIB but
      often leads to early termination of experiments due to animal welfare concerns.
      The aim of this study was to investigate abnormalities associated with the
      urinary retention. Necropsies were performed on 9-mo-old mice; urinalysis,
      hematology and blood chemistry parameters were evaluated, and urogenital
      specimens were microscopically examined. Histopathologic examinations of urinary
      tract specimens proved illuminating regarding pathology in the urinary tract. A
      large mononuclear cell infiltrate was discovered in mutant mice of both sexes,
      more pronounced in females compared with male mice. The infiltrate comprises of
      large rounded or polygonal cells with generous variably vacuolated, granular
      eosinophilic cytoplasm and small round vesicular nuclei. These cells were present
      throughout and expand the interstitium of the lower urinary tract. Either this
      results in extrinsic compression of the lumen of the urethra, eventually leading
      to obstructive uropathy, bladder hyperdistension, and urinary retention or
      possibly interferes with the neurogenic component of micturition needs to be
      further investigated. The novel finding of an unexpected mononuclear cell
      infiltrate in the urinary tract in the knockout mice B6.129S6- Naglu(tm1Efn)/J is
      reported.

PMID- 19389306
TI  - Effect of inositol hexaphosphate on the development of UVB-induced skin tumors in
      SKH1 hairless mice.
AB  - Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated
      carbohydrate that is abundant in many plants and in various high-fiber foods,
      such as cereals and legumes. IP6 has a striking, broad-spectrum anticancer
      activity in various in vitro and animal models, in which it interferes with key
      pathways in malignancy to inhibit cell proliferation, cell-cycle progression,
      metastasis, invasion, and angiogenesis and to induce apoptosis. In this study, we
      investigated the protective effects of IP6 in drinking water on the incidence of
      UVB-induced skin cancer in the SKH1 (Crl: SKH1-hr) mouse model. One group of 15
      mice received 2% IP6 in drinking water and UVB exposure, and the other group (n =
      15) received UVB exposure only. All mice in both groups were fed an IP6-deficient
      diet (AIN 76A). The treatment group started receiving 2% IP6 in the drinking
      water 3 d before irradiation. Mice were irradiated 3 times each week, starting at
      a dose of 1.5 kJ/m2, with weekly increases in increments of 1.5 kJ/m2 to a final
      dose of 7.5 kJ/m2. Tumor formation was monitored until the week 31. IP6 in
      drinking water significantly decreased tumor incidence by 5-fold and tumor
      multiplicity by 4-fold. These results show that IP6 has an antiphotocarcinogenic
      effect and can protect against UVB-induced tumor formation.

PMID- 19389307
TI  - Intestinal cytokine mRNA expression in canine inflammatory bowel disease: a meta
      analysis with critical appraisal.
AB  - Data implicating mucosal cytokines in the pathogenesis of canine inflammatory
      bowel disease (IBD) are limited. The aims of the present study were to report new
      findings of intestinal cytokine expression in dogs with IBD and to compare these
      data with previous studies through meta-analysis. Cytokine mRNA abundance in
      intestinal biopsies collected prospectively was evaluated by using a
      semiquantitative RT-PCR technique. For meta-analysis, an electronic database
      search revealed 3 clinical trials, all of which were nonrandomized (type III)
      case series. Prospective analysis showed that the intestines of healthy dogs and
      those with IBD express numerous cytokines and that a proinflammatory expression
      profile is not a feature of small or large-intestinal IBD. The meta-analysis data
      included 158 dogs characterized as healthy (n = 45), diarrheic nonIBD dogs (n =
      6), nonresponders (n = 2), small-intestinal IBD (n = 41), colonic IBD (n = 25),
      and chronic enteropathy (n = 39). German shepherd dogs were overrepresented in 3
      of the 4 studies. Healthy dogs showed mRNA expression for most cytokines
      including IL2, IL4, IL5, IL10, IL12, IFNgamma, TNFalpha, and TGFbeta. Only IL12
      mRNA expression was increased consistently in small-intestinal IBD, whereas IBD
      colitis lacked consistent patterns of expression. In summary, dogs with IBD fail
      to express a predominant Th1- or Th2 cytokine bias in inflamed mucosa.
      Heterogeneity of results among these studies might be explained by numerous
      factors including the method of mRNA quantification, stage of disease, and
      demographic differences in study populations.

PMID- 19389308
TI  - Bovine colostral antibody against verotoxin 2 derived from Escherichia coli
      O157:H7: resistance to proteases and effects in beagle dogs.
AB  - A bovine colostral antibody against verotoxin (VT) 2 of Escherichia coli O157:H7
      was administered orally to beagle dogs. The antibody remained in the dogs' small
      intestine for at least 2 h, whereas little serum antibody remained 1.5 h after
      administration. Furthermore, the antibody activity of secretory IgA did not
      change until 2 h after administration; however, the activity of IgG and IgM
      antibodies decreased by approximately 60% and 40% at 2 h after administration,
      respectively. Seven beagle dogs inoculated with Escherichia coli O157:H7
      producing VT2 were administered bovine colostral antibody or bovine colostral
      whey without antibody. With administration of bovine colostral whey without
      antibody, the amount of VT2 in feces decreased gradually after administration and
      increased again at 5 d after inoculation, whereas bovine colostral antibody
      significantly reduced the amount of VT2 in feces on the day after administration.
      In addition, 9 beagle dogs were given bovine colostral antibody, bovine plasma
      antibody, or saline. The amount of VT2 in feces again decreased significantly
      more rapidly after administration of bovine colostral antibody than after
      administration of bovine plasma antibody or saline.

PMID- 19389309
TI  - Serologic evaluation of clinical and subclinical secondary hepatic amyloidosis in
      rhesus macaques (Macaca mulatta).
AB  - Secondary hepatic amyloidosis in nonhuman primates carries a grave prognosis once
      animals become clinically ill. The purpose of this study was to establish
      serologic parameters that potentially could be used to identify rhesus macaques
      undergoing subclinical development of secondary hepatic amyloidosis. A
      retrospective analysis was completed by using serum biochemical profiles from 26
      histologically diagnosed amyloidotic macaques evaluated at 2 stages of disease,
      clinical and subclinical (3 to 32 mo prior to clinical signs of disease).
      Standard serum biochemistry values for cases were compared with institutional age
      and gender-specific references ranges by construction of 95% confidence
      intervals for the difference between means. In addition, 19 histologically
      diagnosed amyloidotic macaques and 19 age-matched controls were assayed for
      changes in various parameters by using routinely banked, frozen (-80 degrees C)
      sera available from clinical and subclinical time points. Clinically amyloidotic
      animals displayed increased levels of alkaline phosphatase, aspartate
      aminotransferase, lactate dehydrogenase, gamma glutamyltranspeptidase, and
      macrophage colony-stimulating factor and significantly decreased quantities of
      albumin and total cholesterol. Subclinical amyloidotic animals displayed
      increased levels of alkaline phosphatase, aspartate aminotransferase, lactate
      dehydrogenase, and serum amyloid A and decreased concentrations of albumin and
      total cholesterol. The serologic parameters studied indicate a temporal
      relationship of these factors not previously described, show a clear pattern of
      disease progression, and could be useful in subclinical disease detection.

PMID- 19389310
TI  - Treatment of giardiasis in common marmosets (Callithrix jacchus) with tinidazole.
AB  - Giardia intestinalis is a common protozoan parasite that can infect many
      laboratory animal primates, although its role as a contributor to the induction
      of gastrointestinal disease remains unclear. This study sought to investigate the
      prevalence of Giardia in a colony of common marmosets by using a Giardia antigen
      capture assay and to address the possible eradication of this infection by using
      tinidazole, an antiprotozoal similar to metronidazole but requiring fewer doses.
      Among 31 colony marmosets, 13 (42%) were positive for Giardia. Two doses of oral
      tinidazole eliminated the infection in all animals. Repeat testing of the 13
      Giardia-positive monkeys 1 y later showed that 11 remained negative and that
      treated animals had a significant increase in weight at 1 y. Giardia antigen is
      common in common marmoset feces, and treatment using oral tinidazole is possible
      and highly effective.

PMID- 19389311
TI  - Mousepox detected in a research facility: case report and failure of mouse
      antibody production testing to identify Ectromelia virus in contaminated mouse
      serum.
AB  - An outbreak of mousepox in a research institution was caused by Ectromelia
      contaminated mouse serum that had been used for bone marrow cell culture and the
      cells subsequently injected into the footpads of mice. The disease initially was
      diagnosed by identification of gross and microscopic lesions typical for
      Ectromelia infection, including foci of necrosis in the liver and spleen and
      eosinophilic intracytoplasmic inclusion bodies in the skin. The source of
      infection was determined by PCR analysis to be serum obtained from a commercial
      vendor. To determine whether viral growth in tissue culture was required to
      induce viral infection, 36 mice (BALB/cJ, C57BL/6J) were experimentally exposed
      intraperitoneally, intradermally (footpad), or intranasally to contaminated serum
      or bone marrow cell cultures using the contaminated serum in the culture medium.
      Mice were euthanized when clinical signs developed or after 12 wk. Necropsy, PCR
      of spleen, and serum ELISA were performed on all mice. Mice injected with cell
      cultures and their cage contacts developed mousepox, antibodies to Ectromelia,
      and lesions, whereas mice injected with serum without cells did not. Mouse
      antibody production, a tool commonly used to screen biologic materials for viral
      contamination, failed to detect active Ectromelia contamination in mouse serum.

PMID- 19389312
TI  - Ralstonia pickettii-induced ataxia in immunodeficient mice.
AB  - We report here the characterization of an asymmetric ataxia syndrome (head tilt
      and circling, with death in the most severe cases) demonstrated by profoundly
      immunodeficient mice housed at the Institut Curie SPF facility. The immune system
      of the affected mice had been genetically modified so that they were deficient in
      both B and T cells. Extensive bacteriologic, parasitic, serologic, and
      histopathologic analysis of the affected animals and their healthy controls led
      us to identify Ralstonia pickettii as the causative agent of the ataxic syndrome.
      The outbreak was managed through a test-and-cull process. Even though they also
      carried Ralstonia pickettii, immunocompetent mice that were kept in the same
      facility, did not show any of the signs that were expressed by their
      immunodeficient counterparts. This case highlights the difficulty of maintaining
      immunocompetent and immunodeficient mice in the same microbiologic unit and the
      importance of enlarging the spectrum of health monitoring to opportunistic agents
      when investigating clinical cases in populations of immunocompromised rodents.

PMID- 19389313
TI  - Obesity among adults in the United States--no statistically significant change
      since 2003-2004.
AB  - Over 34% of adults aged 20 years and older are obese, but there has been no
      significant change in the prevalence since 2003-2004. The increasing trend in
      obesity over the last 25 years is a result of a shift in the entire BMI
      distribution and an increase in the prevalence of those who are extremely obese.
      In addition, disparities continue to exist. Non-Hispanic black and Mexican
      American women continue to experience a higher prevalence of obesity than their
      non-Hispanic white counterparts. Although approximately two-thirds of obese
      individuals have been told by a health care provider that they are "overweight,"
      obesity is extremely difficult to treat and the prevalence of obesity is not
      declining. Nonetheless, even without reaching ideal weight, research has shown
      that a moderate amount of weight loss can be beneficial in terms of reducing risk
      factors, such as high blood pressure. Maintenance of weight loss, however,
      remains difficult.

PMID- 19389314
TI  - High serum total cholesterol--an indicator for monitoring cholesterol lowering
      efforts: U.S. adults, 2005-2006.
AB  - Elevated serum total cholesterol is a major and modifiable risk factor for heart
      disease, the lead-ing cause of death in the United States (1,2). Reducing mean
      total serum cholesterol levels among adults to less than 200 mg/dL and reducing
      the proportion who have levels of 240 mg/dL or higher to less than 17% are
      national Healthy People 2010 objectives (3). Age-adjusted mean serum cholesterol
      levels among adults aged 20-74 years declined from 222 mg/dL in 1960-1962 to 203
      mg/dL in 1999-2002 (4). Among adults aged 20 years and older, the percent of the
      population with high serum total cholesterol levels (240 mg/dL or higher)
      declined from 20% during 1988-1994 to 17% during 1999-2002 (4). In individual
      patients, a high serum total cholesterol level indicates a potential increased
      risk for heart disease, but further evaluation of other risk factors and the
      specific components of cholesterol provide the basis for determining the need for
      initiating therapeutic lifestyle changes or treatment with medication (5). Low
      density-lipoprotein (LDL) is the cholesterol component associated with arterial
      blockage, and it is the primary clinical target for cholesterol management. High
      density-lipoprotein (HDL) may help to protect individuals from developing heart
      disease. In populations, comparisons of total cholesterol levels over time can
      show if population groups are experiencing improvement in cholesterol levels, and
      knowledge of trends in levels of total cholesterol can help identify subgroups
      where additional prevention efforts may be needed.

PMID- 19389315
TI  - Food allergy among U.S. children: trends in prevalence and hospitalizations.

PMID- 19389316
TI  - Marital status is associated with health insurance coverage for working-age women
      at all income levels, 2007.

PMID- 19389317
TI  - Hypertension awareness, treatment, and control--continued disparities in adults:
      United States, 2005-2006.
AB  - KEY FINDINGS: Data from the National Health and Nutrition Examination Surveys. In
      2005-2006, 29% of all U.S. adults 18 years and older were hypertensive (systolic
      BP =/> 140 mmHg or diastolic BP =/> 90 mmHg or taking medications for
      hypertension). The prevalence of hypertension was nearly equal between men and
      women. In 2005-2006, an additional 28% of U.S. adults had prehypertension
      (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg, and not pharmacologically
      treated for high BP). In 2005-2006, 7% of the total U.S. adult population had a
      systolic BP =/> 140 mmHg or diastolic BP =/> 90 mmHg, but had never been told by
      a health care provider that they had high BP. Among hypertensive adults, 78% were
      aware of their condition. Overall, 68% of adults with hypertension were using
      anti-hypertensive medication. Over 64% of adults who were taking antihypertensive
      medication achieved BP less than 140/90 mm Hg.

PMID- 19389318
TI  - HIV infection in the United States household population aged 18-49 years: results
      from 1999-2006.
AB  - Data from the National Health and Nutrition Examination Surveys (NHANES). The
      prevalence of HIV infection among adults aged 18-49 years residing in households
      in the United States was 0.47% for the period 1999-2006. Men were more likely to
      be HIV positive than women. Race/ethnic disparities in HIV infection were also
      seen. Non-Hispanic blacks were more likely to be HIV positive than all other
      race/ethnic groups. Infection with HSV-2 was significantly associated with HIV
      infection among the total population aged 18-49 years and especially so among the
      non-His-panic black population. In 1999-2006, nearly one-quarter of HIV-positive
      individuals but only 1% of the HIV-negative individuals aged 18-49 years had low
      CD4 counts (a marker of decreased immune function). Approximately one-third of
      HIV-positive persons had healthy immune systems as compared with 90% among those
      HIV negative.

PMID- 19389319
TI  - Breastfeeding in the United States: findings from the national health and
      nutrition examination surveys, 1999-2006.
AB  - KEY FINDINGS: Data from the National Health and Nutrition Examination Surveys.
      The percentage of infants who were ever breastfed increased from 60% among
      infants who were born in 1993-1994 to 77% among infants who were born in 2005
      2006. Breastfeeding rates increased significantly among non-Hispanic black women
      from 36% in 1993-1994 to 65% in 2005-2006. Breastfeeding rates in 1999-2006 were
      significantly higher among those with higher income (74%) compared with those who
      had lower income (57%). Breastfeeding rates among mothers 30 years and older were
      significantly higher than those of younger mothers. There was no significant
      change in the rate of breast-feeding at 6 months of age for infants born between
      1993 and 2004. Human milk is the ideal food for most infants. Breastfeeding
      benefits infants and their mothers. Breastfed infants receive anti-bodies from
      breast milk, which protect against infection in the early postpartum period, and
      breastfeeding is less expensive than formula feeding. This report summarizes
      information on breastfeeding rates in the United States based on data from the
      1999-2006 National Health and Nutrition Examination Surveys (NHANES). Results are
      reported for the total U.S. population and three race-ethnic groups by birth year
      cohort.

PMID- 19389320
TI  - Blood folate levels: the latest NHANES results.
AB  - Data from the National Health and Nutrition Examination Surveys. Very large
      increases in blood folate levels of the U.S. population occurred between 1988
      1994 and 1999-2000. Small fluctuations in blood folate levels occurred over the
      time period 1999-2006. The median red blood cell (RBC) folate level of the U.S.
      population 4 years of age and older was 266 ng/mL in 2005-2006. The median serum
      folate level of the U.S. population 4 years of age and older was 12.2 ng/mL in
      2005-2006. In 2005-2006, the prevalence of low RBC folate (less than 140 ng/mL)
      among U.S. women of childbearing age (15-45 years) was 4.5%. In 2005-2006, the
      prevalence of low serum folate (less than 3 ng/mL) among U.S. women of
      childbearing age was 0.5%. Folate is an essential vitamin for good health. Women
      of childbearing age are among the population subgroups that have been shown
      previously to have low blood folate levels. Low blood folate levels are
      associated with an increased risk of neural tube birth defects. Beginning in
      1998, the Food and Drug Administration (FDA) required the addition of folic acid
      (a form of folate) to all enriched breads, cereals, flours, corn meal, pasta
      products, rice, and other cereal grain products sold in the United States. Blood
      folate data from the National Health and Nutrition Examination Surveys (NHANES)
      have documented improvements in the folate status of the U.S. population after
      folate fortification was implemented. Red blood cell (RBC) folate measures long
      term folate intake and low levels are associated with adverse health effects.
      Serum folate reflects recent folate intake and low levels are an early indicator
      of inadequate folate status. Pre- and postfortification blood folate levels of
      the U.S. population 4 years of age and older and prevalence of low blood folate
      among women of childbearing age (15-45 years) are reported.

PMID- 19389321
TI  - Depression in the United States household population, 2005-2006.
AB  - KEY FINDINGS: Data from the National Health and Nutrition Examination Survey,
      2005-2006. In any 2-week period, 5.4% of Americans 12 years of age and older
      experienced depression. Rates were higher in 40-59 year olds, women, and non
      Hispanic black persons than in other demographic groups. Rates of depression were
      higher among poor persons than among those with higher incomes. Approximately 80%
      of per sons with depression reported some level of functional impairment because
      of their depression, and 27% reported serious difficulties in work and home life.
      Only 29% of all persons with depression reported contacting a mental health
      professional in the past year, and among the subset with severe depression, only
      39% reported contact. Depression is a common and debilitating illness. It is
      treatable, but the majority of persons with depression do not receive even
      minimally adequate treatment. Depression is characterized by changes in mood,
      self-attitude, cognitive functioning, sleep, appetite, and energy level. The
      World Health Organization found that major depression was the leading cause of
      disability worldwide. Depression causes suffering, decreases quality of life, and
      causes impairment in social and occupational functioning. It is associated with
      increased health care costs as well as with higher rates of many chronic medical
      conditions. Studies have shown that a high number of depressive symptoms are
      associated with poor health and impaired functioning, whether or not the criteria
      for a diagnosis of major depression are met.

PMID- 19389322
TI  - Use of mental health services in the past 12 months by children aged 4-17 years:
      United States, 2005-2006.
AB  - KEY FINDINGS: Data from the National Health Interview Survey. In 2005-2006, 15%
      of U.S. children aged 4-17 years had parents who talked to a health care provider
      or school staff about their child's emotional or behavioral difficulties. This
      included 18% of boys and 11% of girls. Approximately 5% of children were
      prescribed medication for difficulties with emotions or behavior. A large
      majority of these children (89%) were prescribed medication for difficulties with
      concentration, hyperactivity, or impulsivity, which are symptoms of attention
      deficit-hyperactivity disorder (ADHD). Approximately 5% of children received
      "treatment other than medication" for emotional or behavioral difficulties. Most
      of these children - 60% - received this treatment from a mental health private
      practice, clinic, or center. Mental health, which includes emotional and
      behavioral areas of health, is a critical component of child well-being. It may
      impact children's physical health, relationships, and learning. Appropriate
      treatment and intervention for children with emotional or behavioral difficulties
      has been shown to lessen the impact of mental health problems on school
      achievement, relationships with family members and peers, and risk for substance
      abuse. Early mental health screening and the availability and use of appropriate
      mental health services are among the goals of the President's New Freedom
      Commission on Mental Health.

PMID- 19389323
TI  - Recent trends in infant mortality in the United States.
AB  - KEY FINDINGS: Data from the Linked Birth/Infant Death Data Set and Preliminary
      Mortality Data File, National Vital Statistics System. The U.S. infant mortality
      rate did not decline from 2000 to 2005. Data from the preliminary mortality file
      suggest a 2% decline in the infant mortality rate from 2005 to 2006. The U.S.
      infant mortality rate is higher than those in most other developed countries, and
      the gap between the U.S. infant mortality rate and the rates for the countries
      with the lowest infant mortality appears to be widening. The infant mortality
      rate for non-Hispanic black women was 2.4 times the rate for non-Hispanic white
      women. Rates were also elevated for Puerto Rican and American Indian or Alaska
      Native women. Increases in preterm birth and preterm-related infant mortality
      account for much of the lack of decline in the United States' infant mortality
      rate from 2000 to 2005. Infant mortality is one of the most important indicators
      of the health of a nation, as it is associated with a variety of factors such as
      maternal health, quality and access to medical care, socioeconomic conditions,
      and public health practices. The U.S. infant mortality rate generally declined
      throughout the 20th century. In 1900, the U.S. infant mortality rate was
      approximately 100 infant deaths per 1,000 live births, while in 2000, the rate
      was 6.89 infant deaths per 1,000 live births. However, the U.S. infant mortality
      rate did not decline significantly from 2000 to 2005, which has generated concern
      among researchers and policy makers.

PMID- 19389324
TI  - Who adopts? Characteristics of women and men who have adopted children.
AB  - In 2002, 2 percent of adults aged 18-44 years had adopted children, approximately
      2 million people. Significantly more adopters are men, over age 30, are ever
      married, have biological children, and have ever used infertility services. Women
      who have adopted are older than women who have given birth to a child.
      Significantly more ever-married men have adopted children compared with never
      married men or women in either marital status. Women who have ever used
      infertility services are more likely to have adopted compared with women who have
      not used these services. Men who have adopted are more likely than men who have
      not adopted to have also fathered a child. Hispanic women are significantly less
      likely than non-Hispanic women or men of any race or ethnicity to have adopted
      children. Women with incomes below 150% of the poverty level are significantly
      less likely than women with higher incomes or men, irrespective of poverty
      status, to have adopted children. The percentage of infants relinquished by never
      married mothers has declined to 1.0%, or fewer than 7,000 infants annually.

PMID- 19389325
TI  - Role of international medical graduates providing office-based medical care:
      United States, 2005-2006.
AB  - In 2005-2006, about one-quarter (24.6%) of all visits to office-based physicians
      were to international medical graduates. Hispanic or Latino and Asian or Pacific
      Islander patients made more visits to international medical graduates (24.9%)
      than to U.S. medical graduates (12.4%). International medical graduates also saw
      a higher percentage of visits made by patients expecting to use Medicaid or State
      Children's Health Insurance Program (SCHIP) as their primary payment source (17.6
      %) compared with U.S. medical graduates (10.2 %). In 2005-2006, international
      medical graduates comprised 24.5% of all office-based physicians. International
      medical graduates were more likely to be of Asian or Pacific Islander (31.6 %
      compared with 4.9 % of U.S. medical graduates) and Hispanic or Latino descent
      (6.7 % compared with 1.5 % of U.S. medical graduates). International medical
      graduates were more likely to practice in primary care shortage areas outside of
      metropolitan statistical areas (67.8 %) than U.S. medical graduates (39.8%). Over
      the past 30 years, the number of international medical graduates in the physician
      workforce has steadily increased. Many entered the United States on visas that
      allowed them to stay in the United States if they agreed to work in an
      underserved area for 3 years following residency. During the last decade,
      however, the number of international medical graduates on these visas declined by
      47% as use of less-restrictive temporary specialized worker visas increased. The
      declining number of international medical graduates serving in underserved areas
      has made recruiting physicians in these areas more difficult. In order to examine
      the overall role of international medical graduates in providing office-based
      medical care, this Data Brief compares patient and physician characteristics for
      office-based international medical graduates with those of U.S. medical
      graduates.

PMID- 19389326
TI  - Pressure ulcers among nursing home residents: United States, 2004.
AB  - Data from the National Nursing Home Survey, 2004. In 2004, about 159,000 current
      U.S. nursing home residents (11%) had pressure ulcers. Stage 2 pressure ulcers
      were the most common. Residents aged 64 years and under were more likely than
      older residents to have pressure ulcers. Residents of nursing homes for a year or
      less were more likely to have pressure ulcers than those with longer stays. One
      in five nursing home residents with a recent weight loss had pressure ulcers.
      Thirty-five percent of nursing home residents with stage 2 or higher (more
      severe) pressure ulcers received special wound care services in 2004. Pressure
      ulcers, also known as bed sores, pressure sores, or decubitus ulcers, are wounds
      caused by unrelieved pressure on the skin. They usually develop over bony
      prominences, such as the elbow, heel, hip, shoulder, back, and back of the head.
      Pressure ulcers are serious medical conditions and one of the important measures
      of the quality of clinical care in nursing homes. From about 2% to 28% of nursing
      home residents have pressure ulcers. The most common system for staging pressure
      ulcers classifies them based on the depth of soft tissue damage, ranging from the
      least severe to the most severe. There is persistent redness of skin in stage 1;
      a loss of partial thickness of skin appearing as an abrasion, blister, or shallow
      crater in stage 2; a loss of full thickness of skin, presented as a deep crater
      in stage 3; and a loss of full thickness of skin exposing muscle or bone in stage
      4. Clinical practice guidelines for pressure ulcers have been developed and
      provide specific treatment recommendations for stage 2 or higher pressure ulcers,
      including proper wound care. This Data Brief presents the most recent national
      estimates of pressure ulcer prevalence, resident characteristics associated with
      pressure ulcers, and the use of wound care services in U.S. nursing homes.

PMID- 19389327
TI  - Consumer-directed health care for persons under 65 years of age with private
      health insurance: United States, 2007.
AB  - Data from the National Health Interview Survey. In 2007, 17.3% of persons under
      65 years of age with private health insurance were enrolled in a high deductible
      health plan (HDHP), 4.5% were enrolled in a consumer-directed health plan (CDHP),
      and 14.8% were in a family with a flexible spending account for medical expenses
      (FSA); Persons with directly purchased private health insurance were more likely
      to be enrolled in a high deductible plan than those who obtained their private
      health insurance through an employer or union; Higher incomes and higher
      educational attainment were associated with greater uptake and enrollment in
      HDHPs, CDHPs, and FSAs. National attention to consumer-directed health care has
      increased following the enactment of the Medicare Prescription Drug Improvement
      and Modernization Act of 2003 (P.L. 108-173), which established tax-advantaged
      health savings accounts (1). Consumer-directed health care enables individuals to
      have more control over when and how they access care, what types of care they
      use, and how much they spend on health care services. This report includes
      estimates of three measures of consumer-directed private health care. Estimates
      for 2007 are provided for enrollment in high deductible health plans (HDHPs),
      plans with high deductibles coupled with health savings accounts also known as
      consumer-directed health plans (CDHPs), and the percentage of individuals with
      private coverage whose family has a flexible spending account (FSA) for medical
      expenses, by selected sociodemographic characteristics.

PMID- 19389328
TI  - The challenge of fetal mortality.
AB  - Data from the Fetal Death Data File and Linked Birth/Infant Death Data Set,
      National Vital Statistics System. The magnitude of fetal mortality is
      considerable: About 1 million fetal deaths occur at any gestational age in the
      United States each year, including almost 26,000 at 20 weeks of gestation or
      more; Even when limited to fetal deaths of 20 weeks of gestation or more, nearly
      as many fetal deaths as infant deaths occur in the United States each year; After
      decades of decline, the U.S. fetal mortality rate (fetal deaths of 20 weeks of
      gestation or more) did not decrease from 2003 to 2005; Fetal mortality rates are
      substantially higher for non-Hispanic black and American Indian or Alaska Native
      women than for non-Hispanic white women; Compared with the U.S. average, fetal
      mortality rates are higher for teenagers and for women aged 35 years and over,
      for twin and higher-order pregnancies, and for women with more than two previous
      pregnancies. Fetal mortality is a major, but often overlooked, public health
      problem. Fetal mortality refers to spontaneous intrauterine death at any time
      during pregnancy. Fetal deaths later in pregnancy are sometimes referred to as
      stillbirths (at 20 weeks of gestation or more, or 28 weeks or more, for example).
      Much of the public concern regarding reproductive loss has concentrated on infant
      mortality, as less is known about fetal mortality. However, the impact of fetal
      mortality on U.S. families is considerable.This report examines fetal death data
      from the National Vital Statistics System (NVSS). Vital statistics fetal death
      data are generally presented for fetal deaths of 20 weeks of gestation or more.
      Other data sources provide estimates of fetal deaths for all periods of
      gestation. For example, the National Survey of Family Growth estimates about 1
      million fetal losses per year in the United States, with the vast majority of
      these occurring before 20 weeks of gestation.

PMID- 19389329
TI  - Aripiprazole in children and adolescents with bipolar disorder comorbid with
      attention-deficit/hyperactivity disorder: a pilot randomized clinical trial.
AB  - OBJECTIVE: To assess response to treatment with aripiprazole in children and
      adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity
      disorder (ADHD). METHOD: Children and adolescents were extensively assessed
      according to DSM-IV criteria for bipolar disorder comorbid with ADHD (n = 710).
      Those with this comorbidity who were acutely manic or in mixed states were
      randomly assigned in a 6-week double-blind, placebo-controlled trial to
      aripiprazole (n = 18) or placebo (n = 25). Primary outcome measures were assessed
      weekly and included the Young Mania Rating Scale; the Swanson, Nolan, and Pelham
      Scale-Version IV; and weight. Secondary outcome measures were the Clinical Global
      Impressions-Severity of Illness scale, the Child Mania Rating Scale-Parental
      Version (CMRS-P), the Children's Depression Rating Scale-Revised, the Kutcher
      Adolescent Depression Scale, and adverse events. The trial was conducted at the
      Hospital de Clinicas de Porto Alegre, Rio Grande do Sul, Brazil, from January
      2005 to November 2007. RESULTS: The group receiving aripiprazole showed a
      significantly greater reduction in YMRS scores (P = .02, effect size [ES] =
      0.80), CMRS-P scores (P = .02; ES = 0.54), and CGI-S scores (P = .04; ES = 0.28)
      from baseline to endpoint than the placebo group. In addition, higher rates of
      response (P = .02) and remission (P = .01) were found for the aripiprazole group.
      No significant between-group differences were found in weight, ADHD symptoms, and
      depressive symptoms. Adverse events significantly more frequent in the
      aripiprazole group were somnolence and sialorrhea. CONCLUSION: Aripiprazole was
      effective in reducing manic symptoms and improving global functioning without
      promoting severe adverse events or weight gain. No significant treatment effect
      in ADHD symptoms was observed. Studies are needed to assess psychopharmacologic
      interventions for improving ADHD symptoms in juvenile bipolar disorder comorbid
      with ADHD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00116259.

PMID- 19389330
TI  - The Child Behavior Checklist-Pediatric Bipolar Disorder profile predicts a
      subsequent diagnosis of bipolar disorder and associated impairments in ADHD youth
      growing up: a longitudinal analysis.
AB  - OBJECTIVE: To examine the predictive utility of the Child Behavior Checklist
      Pediatric Bipolar Disorder (CBCL-PBD) profile to help identify children at risk
      for bipolar disorder. METHOD: Subjects were ascertained from 2 identically
      designed longitudinal case-control family studies of subjects (males and females
      aged 6-18 years) with DSM-III-R attention-deficit/hyperactivity disorder (ADHD).
      Based on data from the baseline assessment, ADHD subjects without a lifetime
      diagnosis of bipolar disorder were stratified by the presence (CBCL-PBD positive,
      N=28) or absence (CBCL-PBD negative, N=176) of a CBCL-PBD score > or = 210 (total
      of attention, aggression, and anxious/depressed subscales). Subjects were
      comprehensively assessed at follow-up with structured psychiatric interviews.
      Data were collected from April 1988 to February 2003. RESULTS: Over a mean follow
      up period of 7.4 years, a positive CBCL-PBD score predicted subsequent diagnoses
      of bipolar disorder, major depressive disorder, and conduct disorder, as well as
      impaired psychosocial functioning and higher risk for psychiatric
      hospitalization. CONCLUSION: This work suggests that a positive CBCL-PBD score
      based on elevations on the attention problems, aggressive behavior, and
      anxious/depressed subscales predicts subsequent pediatric bipolar disorder and
      associated syndrome-congruent impairments. If confirmed in other studies, the
      CBCL-PBD score has the potential to help identify children at high risk to
      develop bipolar disorder.

PMID- 19389331
TI  - Akathisia: an updated review focusing on second-generation antipsychotics.
AB  - OBJECTIVE: To provide a brief description of the pathophysiology of akathisia,
      the challenges of diagnosing and treating this condition, and potential
      associated clinical issues. Also, to provide a review of the literature on the
      incidence of drug-induced akathisia associated with the use of second-generation
      antipsychotics (SGAs) and first-generation antipsychotics (FGAs). DATA SOURCES:
      English-language literature with no date restrictions cited in PubMed was
      searched for the keywords akathisia, placebo, neuroleptic, or haloperidol, and
      the generic names of SGAs (clozapine, risperidone, olanzapine, quetiapine,
      ziprasidone, or aripiprazole). STUDY SELECTION: Limits were set to search
      clinical trials, meta-analyses, or randomized controlled trials reviewing data
      from adult schizophrenia or bipolar disorder clinical trials. Studies including
      SGA comparisons with placebo and with FGAs, and also between SGAs themselves,
      were selected. Studies that specifically assessed akathisia (either subjectively
      or objectively or both) were included. Studies reporting generalized results
      pertaining to extrapyramidal symptoms (EPS) were excluded. DATA EXTRACTION: The
      incidence of akathisia, EPS rating scores, and required medications for the
      management of movement disorders were reviewed. DATA SYNTHESIS: Seventy-seven
      trials were included in the comparative review. Akathisia was observed with the
      use of all the SGAs. The akathisia incidence reported in bipolar disorder trials
      was generally higher compared with schizophrenia trials. The incidence reported
      for FGAs was consistently higher than that reported for SGAs, regardless of the
      patient population studied. CONCLUSION: Akathisia remains a concern with the use
      of SGAs. More accurate and standardized evaluations are required for a better
      understanding of the nature and incidence of akathisia.

PMID- 19389332
TI  - A longitudinal study of the effects of lithium treatment on prefrontal and
      subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder
      patients.
AB  - OBJECTIVE: Recent molecular, preclinical, and preliminary clinical studies
      suggest that the therapeutic effects of mood stabilizers may be mediated by
      modulating expression of potent neurotrophic and neuroprotective factors having
      the potential to reverse impairments of cellular resilience, reductions in brain
      volume, and cell death or atrophy. Our main goal was to investigate the potential
      clinical significance of these findings in relation to bipolar disorder. METHOD:
      The longitudinal effect of lithium on brain gray matter volume was investigated
      in well-characterized (DSM-IV criteria) bipolar depressed subjects (N = 28) at
      baseline (medication-free) and after lithium administration (4 weeks). Total
      brain gray matter, prefrontal gray matter, and left subgenual prefrontal gray
      matter volumes were determined using validated semiautomated segmentation and
      region of interest methodology. The study was conducted from November 1997 until
      April 2004 at Wayne State University School of Medicine, Detroit, Mich. RESULTS:
      Significant increases in total brain gray matter volume in bipolar subjects were
      observed after 4 weeks of lithium administration (p = .0043). Moreover, regional
      analyses in the bipolar subjects revealed significant differences between
      responders (>50% decrease in Hamilton Depression Rating Scale total score) and
      nonresponders; only responders showed a significant increase in gray matter
      volume in the prefrontal cortex (p = .003) and an increase at trend level in the
      left subgenual prefrontal cortex volume (p = .0786). CONCLUSION: The increase in
      gray matter volume in these areas, which various neuroimaging and postmortem
      neuropathology studies have implicated in the neuropathophysiology of bipolar
      disorder, suggests that the observed effects may be linked to clinical response.
      The findings also support the notion that future treatments that more directly
      target molecules in critical central nervous system pathways that regulate
      cellular plasticity hold promise as novel, improved, long-term treatments for
      mood disorders as well as some neurodegenerative conditions, such as Alzheimer's
      disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00870311.

PMID- 19389333
TI  - A double-blind, randomized, placebo-controlled trial of fluoxetine in patients
      with intermittent explosive disorder.
AB  - BACKGROUND: Intermittent explosive disorder (IED) is a disorder of impulsive
      aggression that affects as many as 7.3% of the U.S. population during some period
      of life. Since central serotonergic (5-HT) system dysfunction is related to
      impulsive aggressive behavior, pharmacologic enhancement of 5-HT activity should
      reduce impulsive aggressive behavior in individuals with IED. METHOD: A double
      blind, randomized, placebo-controlled trial of the selective 5-HT uptake
      inhibitor fluoxetine was conducted in 100 individuals with IED (research
      diagnostic criteria) and current histories of impulsive aggressive behavior. The
      primary efficacy measure was the aggression score from the Overt Aggression Scale
      Modified (OAS-M) for Outpatient Use. Secondary efficacy measures included the
      irritability score from the OAS-M and the Clinical Global Impressions-Improvement
      scale (CGI-I) score. The study took place between July 1990 and July 1999.
      RESULTS: Fluoxetine treatment resulted in a sustained reduction in OAS-M
      aggression, and OAS-M irritability scores, apparent as early as week 2 (p < .01
      for aggression and p < .001 for irritability at endpoint). Fluoxetine was also
      superior to placebo in the proportion of responders on the CGI-I (p < .001).
      Closer examination of the data revealed that full or partial remission of
      impulsive aggressive behaviors, as reflected by the A criteria for IED, occurred
      in 46% of fluoxetine-treated subjects. Fluoxetine did not exert an antidepressant
      or antianxiety effect, and its effects on impulsive aggression were not
      influenced by presence of current symptoms of depression or anxiety. CONCLUSION:
      Fluoxetine treatment has a clear antiaggressive effect in impulsive aggressive
      individuals with IED. However, while fluoxetine's antiaggressive effects appear
      robust, they lead to full or partial remission of IED in less than 50% of
      subjects treated with fluoxetine.

PMID- 19389334
TI  - Benzodiazepine use and driving: a meta-analysis.
AB  - OBJECTIVE: The purpose of the present study was to examine the experimental and
      epidemiologic evidence linking benzodiazepine use to driving impairment. DATA
      SOURCES: We searched MEDLINE, PsycINFO, the Cochrane Collaboration, and EMBASE
      using the key terms ("benzodiazepines" OR "exp benzodiazepines") AND ("automobile
      driving" OR "accidents, traffic" OR "driving" OR "driver$") and limited the
      results to English citations from 1966 to August 5, 2005, with auto-updates for
      MEDLINE and PsycINFO to November 30, 2007. STUDY SELECTION AND DATA EXTRACTION:
      Experimental studies using driving simulators and on-road tests were sought, as
      were epidemiologic studies of a case-control or cohort design. Data were
      extracted by blinded raters and pooled using random-effects models. We excluded
      studies without control groups or without measures of driving or collisions.
      Studies with driving measures that could not be combined were also excluded. DATA
      SYNTHESIS: Of 405 potential articles, 11 epidemiologic and 16 experimental
      studies were included in the meta-analysis. Associations between motor vehicle
      collisions (MVCs) and benzodiazepine use were found among 6 case-control studies
      (OR = 1.61, 95% CI = 1.21 to 2.13, p <.001), and 3 cohort studies (OR = 1.60, 95%
      CI = 1.29 to 1.97, p <.0001). Only 10 of 97 experimental driving variables could
      be pooled for analysis. While no consistent findings were observed in studies
      using driving simulators, increased deviation of lateral position was found on on
      road driving tests (standardized mean difference = 0.80, 95% CI = 0.35 to 1.25, p
      = .0004). CONCLUSION: Benzodiazepine users were found to be at a significantly
      increased risk of MVCs compared to nonusers, and these differences may be
      accounted for by a difficulty in maintaining road position.

PMID- 19389335
TI  - Neurocognitive effectiveness of haloperidol, risperidone, and olanzapine in first
      episode psychosis: a randomized, controlled 1-year follow-up comparison.
AB  - OBJECTIVE: To investigate the neurocognitive effectiveness of haloperidol,
      risperidone, and olanzapine in first-episode schizophrenia-spectrum disorders.
      METHOD: This prospective, randomized, open-label study was conducted from
      February 2001 to February 2005. Data for the present investigation were obtained
      from a large epidemiologic and 3-year longitudinal intervention program of first
      episode psychosis (DSM-IV criteria) conducted at the outpatient clinic and the
      inpatient unit at the University Hospital Marques de Valdecilla, Santander,
      Spain. One hundred four patients randomly assigned to haloperidol (N = 35),
      olanzapine (N = 30), or risperidone (N = 39) who completed clinical and cognitive
      evaluations at baseline, 6 months, and 1 year were included in the final
      analysis. Thirty-seven healthy individuals were also longitudinally assessed. A
      neuropsychological battery that comprised 9 cognitive domains was used. The
      contribution of clinical changes, concomitant medications, and the severity of
      motor side effects to cognitive changes was controlled. The main outcome measure
      was cognitive changes at 1-year follow-up. RESULTS: The 3 treatment groups showed
      a significant improvement in cognitive scores after 1 year. The differential
      cognitive effectiveness between antipsychotics was insignificant. The magnitude
      of cognitive changes was similar in the 3 treatment groups and controls, although
      a greater improvement on the Finger Tapping Test, Trail Making Test B, and Rey
      Complex Figure Test was found in the treatment groups. Clinical changes, use of
      concomitant medications, and the emergence of motor side effects did not
      significantly account for cognitive changes over time. CONCLUSION: Haloperidol,
      olanzapine, and risperidone were equally effective in treating cognitive deficits
      of psychosis. The effect of practice clearly contributes to cognitive score
      improvements after treatment with antipsychotics. Our results provide important
      information regarding the practical utility of antipsychotic treatments to
      improve cognition and could have implications for developing novel approaches for
      cognitive pharmacotherapy in schizophrenia.

PMID- 19389336
TI  - Refining posttraumatic stress disorder diagnosis: evaluation of symptom criteria
      with the National Survey of Adolescents.
AB  - OBJECTIVE: To compare the prevalence estimates, comorbidity rates, and structural
      validity of a revised symptom criteria set for the diagnosis of posttraumatic
      stress disorder (PTSD) with those of the DSM-IV criteria in a representative
      community sample of adolescents. METHOD: Cross-sectional data from the National
      Survey of Adolescents, a 1995 household probability sample of 4,023 adolescents
      aged 12-17 years, were examined. DSM-IV PTSD symptoms were assessed with a
      modification of the National Women's Study PTSD module. Three- and 4-factor DSM
      IV models were compared to a 2-factor PTSD model that deleted symptoms
      potentially overlapping with depression or other anxiety disorders. Comorbidity
      was assessed using DSM-IV criteria for major depressive episodes and substance
      use disorders. RESULTS: PTSD prevalence varied across models (ie, 5.2%-8.8%,
      lifetime; 3.2%-5.7%, past 6 months). When the 2-factor model was used with a
      proportionate symptom threshold, lifetime PTSD prevalence was comparable to that
      with the 3-factor DSM-IV model, and major depressive episode comorbidity was
      reduced by 9%-14%. Comorbidity with substance use disorders was comparable across
      models. Structural validity, tested with confirmatory factor analyses, showed
      that the 2-factor model and a 4-factor DSM-IV model were superior to the DSM-IV 3
      factor model. CONCLUSION: Compared to the DSM-IV 3-factor PTSD model, a 2-factor
      model that removed depression and anxiety symptoms and used a proportionate
      symptom threshold may produce comparable lifetime PTSD prevalence estimates,
      reduced PTSD-depression comorbidity, and superior structural validity (comparable
      to a 4-factor PTSD model) when applied to community samples of adolescents.
      Further research on PTSD structure and diagnosis with adolescents is warranted.

PMID- 19389337
TI  - VACSATC (vaccine safety: attitudes, training and communication): why such a
      project?
AB  - The Vaccine safety: attitudes, training and communication (VACSATC) project was
      established in 2006 to study perceptions of immunisation and vaccine safety, to
      improve training of healthcare professionals on vaccine safety and to improve the
      availability of information on vaccine safety on the internet that adheres to
      good information practices. The three year project is funded by the European
      Commission's Directorate General for Health and Consumers and by the partners.
      The project complements the activities of the Vaccine Safety Net project and the
      Vaccine European New Integrated Collaboration Effort (VENICE) project.

PMID- 19389338
TI  - Characterisation of Neisseria meningitidis C strains causing two clusters in the
      north of Italy in 2007 and 2008.
AB  - Two clusters of invasive meningococcal disease in the north of Italy both due to
      serogroup C/ST-11 clonal complex are here described. The objective of the
      investigation was to analyse the phenotype and the genotype of meningococci
      involved in the two clusters which were of national relevance due to the fatal
      outcome of the majority of cases (six of the total of 10 cases). All the strains
      were C:2a:P1.5 ST-11/ET-37 clonal complex. Two pulsed field gel electrophoresis
      (PFGE) and variable number tandem repeats (VNTR) profiles were identified, one
      for each cluster. VNTRs were different from those detected in Italy for C/ST-11
      strains isolated from sporadic cases in the same period. This laboratory
      surveillance report highlights the importance and the crucial role of molecular
      characterisation to confirm the relatedness among meningococci responsible for
      clusters of cases.

PMID- 19389339
TI  - Mumps epidemiology in the mid-west of Ireland 2004-2008: increasing disease
      burden in the university/college setting.
AB  - Mumps is a contagious vaccine-preventable viral disease that is experiencing a
      revival in students attending second and third level colleges. Large mumps
      outbreaks have been reported in several countries despite the presence of
      childhood immunisation programmes over many years, including measles, mumps, and
      rubella (MMR) vaccination. In 2008, 1,377 cases of mumps were notified in Ireland
      and 1,734 in the first three months of 2009 (provisional data). This paper
      reviews the recent epidemiology of mumps in the Mid-West region of Ireland and
      highlights preventive measures. A substantial proportion of cases were not
      laboratory-confirmed and it is important that doctors continue to notify
      suspected cases. In the Irish Mid-West, data from enhanced surveillance shows a
      high proportion of mumps in the age group 15-24 years. Complications were
      uncommon and rarely severe. Where data were available, over half of the cases did
      not recall having received two doses of MMR, but most recalled one dose. Parents
      should continue to ensure children receive both MMR vaccinations so that uptake
      is optimal for protection. Steps were taken to increase awareness of the disease
      in the school, college and university settings. Preventive measures implemented
      to limit mumps transmission in the school/college setting over recent years
      included vaccination of close contacts, isolation for five days and hand hygiene.

PMID- 19389340
TI  - Ongoing rubella outbreak in Austria, 2008-2009.
AB  - Since October 2008, a total of 143 cases of rubella have affected the two
      Austrian provinces Styria and Burgenland. The index case occurred in mid-October
      2008, but was not notified to the public health authorities until February 2009,
      when the Austrian Agency for Health and Food Safety was asked to investigate a
      cluster of 32 rubella cases (24 laboratory-confirmed and eight clinically
      suspected cases). No case of rubella had been reported in the two affected
      provinces between February 2007 - when statutory notification for rubella was
      implemented - and mid-October 2008. 113 of the 143 cases (79%) were confirmed:
      101 (89.3% of the 113 cases) clinical-laboratory confirmed and 12 clinical
      epidemiological confirmed. Thirty cases fulfilled the criteria of a probable
      outbreak case only (laboratory results or data on epidemiological link are
      pending). For 140 outbreak cases data on age was known; the median age was 19
      years (range: 2-60 years). 20 cases occurred in soldiers in seven military camps
      in the area. 55 cases (38.5 %) were female. One case of a laboratory-confirmed
      rubella infection, affecting an unvaccinated pregnant 18-years old native
      Austrian in the early first trimenon of pregnancy, led to voluntary abortion

PMID- 19389341
TI  - Outbreak of Clostridium difficile 027 in North Zealand, Denmark, 2008-2009.
AB  - We report an outbreak of Clostridium difficile PCR ribotype 027 in Denmark. The
      outbreak includes to date 73 cases from the area north of Copenhagen, but there
      may be related cases elsewhere in Zealand. Most infections are healthcare
      associated and in patients who previously received antibiotic treatment. The
      strain is resistant to moxifloxacin, erythromycin, and clindamycin, and carries
      genes for toxin A, toxin B, and for the binary toxin. The antimicrobial pattern
      differs from that of the strain involved in a small cluster in Denmark in 2006
      2007. Because of this outbreak, hygienic measures in the involved hospitals have
      been reinforced. Nationwide, microbiological laboratories were alerted to the
      outbreak and encouraged to send isolates for toxin profiling and PCR ribotyping.

PMID- 19389342
TI  - European Immunization Week goes viral.

PMID- 19389344
TI  - Spoltud-1 is a chromatoid body component required for planarian long-term stem
      cell self-renewal.
AB  - Freshwater planarians exhibit a striking power of regeneration, based on a
      population of undifferentiated totipotent stem cells, called neoblasts. These
      somatic stem cells have several characteristics resembling those of germ line
      stem cells in other animals, such as the presence of perinuclear RNA granules
      (chromatoid bodies). We have isolated a Tudor domain-containing gene in the
      planarian species Schmidtea polychroa, Spoltud-1, and show that it is expressed
      in neoblast cells, germ line cells and central nervous system, and during
      embryonic development. Within the neoblasts, Spoltud-1 protein is enriched in
      chromatoid bodies. Spoltud-1 RNAi eliminates protein expression after 3 weeks,
      and abolishes the power of regeneration of planarians after 7 weeks. Neoblast
      cells are eliminated by the RNAi treatment, disappearing at the end rather than
      gradually during the process. Neoblasts with no detectable Spoltud-1 protein are
      able to proliferate and differentiate. These results suggest that Spoltud-1 is
      required for long term stem cell self renewal.

PMID- 19389343
TI  - The food contaminant fumonisin B(1) reduces the maturation of porcine CD11R1(+)
      intestinal antigen presenting cells and antigen-specific immune responses,
      leading to a prolonged intestinal ETEC infection.
AB  - Consumption of food or feed contaminated with fumonisin B(1) (FB(1)), a mycotoxin
      produced by Fusarium verticillioides, can lead to disease in humans and animals.
      The present study was conducted to examine the effect of FB1 intake on the
      intestinal immune system. Piglets were used as a target and as a model species
      for humans since their gastro-intestinal tract is very similar. The animals were
      orally exposed to a low dose of FB(1) (1 mg/kg body weight FB(1)) for 10 days
      which did not result in clinical signs. However, when compared to non-exposed
      animals, FB(1)-exposed animals showed a longer shedding of F4(+) enterotoxigenic
      Escherichia coli (ETEC) following infection and a lower induction of the antigen
      specific immune response following oral immunization. Further analyses to
      elucidate the mechanisms behind these observations revealed a reduced intestinal
      expression of IL-12p40, an impaired function of intestinal antigen presenting
      cells (APC), with decreased upregulation of Major Histocompatibility Complex
      Class II molecule (MHC-II) and reduced T cell stimulatory capacity upon
      stimulation. Taken together, these results indicate an FB(1)-mediated reduction
      of in vivo APC maturation.

PMID- 19389345
TI  - Hedgehog does not guide migrating Drosophila germ cells.
AB  - In many species, the germ cells, precursors of sperm and egg, migrate during
      embryogenesis. The signals that regulate this migration are thus essential for
      fertility. In flies, lipid signals have been shown to affect germ cell guidance.
      In particular, the synthesis of geranylgeranyl pyrophosphate through the 3
      hydroxy-3-methyl-glutaryl coenzyme A reductase (Hmgcr) pathway is critical for
      attracting germ cells to their target tissue. In a genetic analysis of signaling
      pathways known to affect cell migration of other migratory cells, we failed to
      find a role for the Hedgehog (Hh) pathway in germ cell migration. However,
      previous reports had implicated Hh as a germ cell attractant in flies and
      suggested that Hh signaling is enhanced through the action of the Hmgcr pathway.
      We therefore repeated several critical experiments and carried out further
      experiments to test specifically whether Hh is a germ cell attractant in flies.
      In contrast to previously reported findings and consistent with findings in
      zebrafish our data do not support the notion that Hh has a direct role in the
      guidance of migrating germ cells in flies.

PMID- 19389346
TI  - BAX-mediated cell death affects early germ cell loss and incidence of testicular
      teratomas in Dnd1(Ter/Ter) mice.
AB  - A homozygous nonsense mutation (Ter) in murine Dnd1 (Dnd1(Ter/Ter)) results in a
      significant early loss of primordial germ cells (PGCs) prior to colonization of
      the gonad in both sexes and all genetic backgrounds tested. The same mutation
      also leads to testicular teratomas only on the 129Sv/J background. Male mutants
      on other genetic backgrounds ultimately lose all PGCs with no incidence of
      teratoma formation. It is not clear how these PGCs are lost or what factors
      directly control the strain-specific phenotype variation. To determine the
      mechanism underlying early PGC loss we crossed Dnd1(Ter/Ter) embryos to a Bax
      null background and found that germ cells were partially rescued. Surprisingly,
      on a mixed genetic background, rescued male germ cells also generated fully
      developed teratomas at a high rate. Double-mutant females on a mixed background
      did not develop teratomas, but were fertile and produced viable off-spring.
      However, when Dnd1(Ter/Ter) XX germ cells developed in a testicular environment
      they gave rise to the same neoplastic clusters as mutant XY germ cells in a
      testis. We conclude that BAX-mediated apoptosis plays a role in early germ cell
      loss and protects from testicular teratoma formation on a mixed genetic
      background.

PMID- 19389347
TI  - Abd-B suppresses lepidopteran proleg development in posterior abdomen.
AB  - Pterygotes lack abdominal appendages except for pleuropods and prolegs. The
      larvae of some holometabolous insects develop prolegs, which are used for
      locomotion. We analyzed the role of the homeotic genes abd-A and Abd-B in
      lepidopteran proleg development using mutant analysis and embryonic RNAi in the
      silkworm Bombyx mori. The E(Mu) mutant developed extra prolegs in its posterior
      abdomen and showed the misexpression of both genes, suggesting their involvement
      in proleg formation. The depletion of Abd-B by embryonic RNAi caused the
      development of extra prolegs on all segments posterior to A6, indicating the
      suppressive function of Abd-B. The abd-A RNAi animals failed to develop prolegs.
      These results indicate that abd-A and Abd-B are involved in proleg development in
      B. mori.

PMID- 19389348
TI  - The Xenopus MEF2 gene family: evidence of a role for XMEF2C in larval tendon
      development.
AB  - MEF2 transcription factors are well-established regulators of muscle development.
      In this report, we describe the cloning of multiple splicing isoforms of the
      XMEF2A and XMEF2C encoding genes, differentially expressed during Xenopus
      development. Using whole-mount in situ hybridization, we found that the
      accumulation of XMEF2C mRNA in the tadpole stages was restricted to intersomitic
      regions and to the peripheral edges of hypaxial and cranial muscle masses in
      contrast to XMEF2A and XMEF2D, characterized by a continuous muscle cell
      expression. The XMEF2C positive cells express the bHLH transcription factor,
      Xscleraxis, known as a specific marker for tendons. Gain of function experiments
      revealed that the use of a hormone-inducible XMEF2C construct is able to induce
      Xscleraxis expression. Furthermore, XMEF2C specifically cooperates with
      Xscleraxis to induce tenascin C and betaig-h3, two genes preferentially expressed
      in Xenopus larval tendons. These findings 1) highlight a previously unappreciated
      and specific role for XMEF2C in tendon development and 2) identify a novel gene
      transactivation pathway where MEF2C cooperates with the bHLH protein, Xscleraxis,
      to activate specific gene expression.

PMID- 19389349
TI  - Phospholipase D1 is required for angiogenesis of intersegmental blood vessels in
      zebrafish.
AB  - Phospholipase D (PLD) hydrolyzes phosphatidylcholine to generate phosphatidic
      acid and choline. Studies in cultured cells and Drosophila melanogaster have
      implicated PLD in the regulation of many cellular functions, including
      intracellular vesicle trafficking, cell proliferation and differentiation.
      However, the function of PLD in vertebrate development has not been explored.
      Here we report cloning and characterization of a zebrafish PLD1 (pld1) homolog.
      Like mammalian PLDs, zebrafish Pld1 contains two conservative HKD motifs.
      Maternally contributed pld1 transcripts are uniformly distributed in early
      embryo. Localized expression of pld1 is observed in the notochord during early
      segmentation, in the somites during later segmentation and in the liver at the
      larval stages. Studies in intact and cell-free preparations demonstrate
      evolutionary conservation of regulation. Inhibition of Pld1 expression using
      antisense morpholino oligonucleotides (MO) interfering with the translation or
      splicing of pld1 impaired intersegmental vessel (ISV) development. Incubating
      embryos with 1-butanol, which diverts production of phosphatidic acid to a
      phosphatidylalcohol, caused similar ISV defects. To determine where Pld1 is
      required for ISV development we performed transplantation experiments. Analyses
      of the mosaic Pld1 deficient embryos showed partial suppression of ISV defects in
      the segments containing transplanted wild-type notochord cells but not in the
      ones containing wild-type somitic cells. These results provide the first evidence
      that function of Pld1 in the developing notochord is essential for vascular
      development in vertebrates.

PMID- 19389350
TI  - Remodeling of insulin producing beta-cells during Xenopus laevis metamorphosis.
AB  - Insulin-producing beta-cells are present as single cells or in small clusters
      distributed throughout the pancreas of the Xenopus laevis tadpole. During
      metamorphic climax when the exocrine pancreas dedifferentiates to progenitor
      cells, the beta-cells undergo two changes. Insulin mRNA is down regulated at the
      beginning of metamorphic climax (NF62) and reexpressed again near the end of
      climax. Secondly, the beta-cells aggregate to form islets. During climax the
      increase in insulin cluster size is not caused by cell proliferation or by acinar
      to-beta-cell transdifferentiation, but rather is due to the aggregation of pre
      existing beta-cells. The total number of beta-cells does not change during the 8
      days of climax. Thyroid hormone (TH) induction of premetamorphic tadpoles causes
      an increase in islet size while prolonged treatment of tadpoles with the
      goitrogen methimazole inhibits this increase. Expression of a dominant negative
      form of the thyroid hormone receptor (TRDN) driven by the elastase promoter not
      only protects the exocrine pancreas of a transgenic tadpole from TH-induced
      dedifferentiation but also prevents aggregation of beta-cells at climax. These
      transgenic tadpoles do however undergo normal loss and resynthesis of insulin
      mRNA at the same stage as controls. In contrast transgenic tadpoles with the same
      TRDN transgene driven by an insulin promoter do not undergo down regulation of
      insulin mRNA, but do aggregate beta-cells to form islets like controls. These
      results demonstrate that TH controls the remodeling of beta-cells through cell
      cell interaction with dedifferentiating acinar cells and a cell autonomous
      program that temporarily shuts off the insulin gene.

PMID- 19389351
TI  - Residual microRNA expression dictates the extent of inner ear development in
      conditional Dicer knockout mice.
AB  - Inner ear development requires coordinated transformation of a uniform sheet of
      cells into a labyrinth with multiple cell types. While numerous regulatory
      proteins have been shown to play critical roles in this process, the regulatory
      functions of microRNAs (miRNAs) have not been explored. To demonstrate the
      importance of miRNAs in inner ear development, we generated conditional Dicer
      knockout mice by the expression of Cre recombinase in the otic placode at E8.5.
      Otocyst-derived ganglia exhibit rapid neuron-specific miR-124 depletion by E11.5,
      degeneration by E12.5, and profound defects in subsequent sensory epithelial
      innervations by E17.5. However, the small and malformed inner ear at E17.5
      exhibits residual and graded hair cell-specific miR-183 expression in the three
      remaining sensory epithelia (posterior crista, utricle, and cochlea) that closely
      corresponds to the degree of hair cell and sensory epithelium differentiation,
      and Fgf10 expression required for morphohistogenesis. The highest miR-183
      expression is observed in near-normal hair cells of the posterior crista, whereas
      the reduced utricular macula demonstrates weak miR-183 expression and develops
      presumptive hair cells with numerous disorganized microvilli instead of ordered
      stereocilia. The correlation of differential and delayed depletion of mature
      miRNAs with the derailment of inner ear development demonstrates that miRNAs are
      crucial for inner ear neurosensory development and neurosensory-dependent
      morphogenesis.

PMID- 19389352
TI  - Germ cell migration in zebrafish is cyclopamine-sensitive but Smoothened
      independent.
AB  - Primordial germ cells (PGCs) are the progenitors of reproductive cells in
      metazoans and are an important model for the study of cell migration in vivo.
      Previous reports have suggested that Hedgehog (Hh) protein acts as a
      chemoattractant for PGC migration in the Drosophila embryo and that downstream
      signaling proteins such as Patched (Ptc) and Smoothened (Smo) are required for
      PGC localization to somatic gonadal precursors. Here we interrogate whether Hh
      signaling is required for PGC migration in vertebrates, using the zebrafish as a
      model system. We find that cyclopamine, an inhibitor of Hh signaling, causes
      strong defects in the migration of PGCs in the zebrafish embryo. However, these
      defects are not due to inhibition of Smoothened (Smo) by cyclopamine; rather, we
      find that neither maternal nor zygotic Smo is required for PGC migration in the
      zebrafish embryo. Cyclopamine instead acts independently of Smo to decrease the
      motility of zebrafish PGCs, in part by dysregulating cell adhesion and uncoupling
      cell polarization and translocation. These results demonstrate that Hh signaling
      is not required for zebrafish PGC migration, and underscore the importance of
      regulated cell-cell adhesion for cell migration in vivo.

PMID- 19389353
TI  - Catweasel mice: a novel role for Six1 in sensory patch development and a model
      for branchio-oto-renal syndrome.
AB  - Large-scale mouse mutagenesis initiatives have provided new mouse mutants that
      are useful models of human deafness and vestibular dysfunction. Catweasel is a
      novel N-ethyl-N-nitrosourea (ENU)-induced mutation. Heterozygous catweasel mutant
      mice exhibit mild headtossing associated with a posterior crista defect. We
      mapped the catweasel mutation to a critical region of 13 Mb on chromosome 12
      containing the Six1, -4 and -6 genes. We identified a basepair substitution in
      exon 1 of the Six1 gene that changes a conserved glutamic acid (E) at position
      121 to a glycine (G) in the Six1 homeodomain. Cwe/Cwe animals lack Preyer and
      righting reflexes, display severe headshaking and have severely truncated cochlea
      and semicircular canals. Cwe/Cwe animals had very few hair cells in the utricle,
      but their ampullae and cochlea were devoid of any hair cells. Bmp4, Jag1 and Sox2
      expression were largely absent at early stages of sensory development and NeuroD
      expression was reduced in the developing vestibulo-acoustic ganglion. Lastly we
      show that Six1 genetically interacts with Jag1. We propose that the catweasel
      phenotype is due to a hypomorphic mutation in Six1 and that catweasel mice are a
      suitable model for branchio-oto-renal syndrome. In addition Six1 has a pivotal
      role in early sensory patch development and may act in the same genetic pathway
      as Jag1.

PMID- 19389354
TI  - Spatio-temporal intersection of Lhx3 and Tbx6 defines the cardiac field through
      synergistic activation of Mesp.
AB  - Mesp encodes a bHLH transcription factor required for specification of the
      cardiac mesoderm in Ciona embryos. The activities of Macho-1 and beta-catenin,
      two essential maternal determinants, are required for Mesp expression in the B7.5
      blastomeres, which constitute the heart field. The T-box transcription factor
      Tbx6 functions downstream of Macho-1 as a direct activator of Mesp expression.
      However, Tbx6 cannot account for the restricted expression of Mesp in the B7.5
      lineage since it is expressed throughout the presumptive tail muscles. Here we
      present evidence that the LIM-homeobox gene Lhx3, a direct target of beta
      catenin, is essential for localized Mesp expression. Lhx3 is expressed throughout
      the presumptive endoderm and B7.5 blastomeres. Thus, the B7.5 blastomeres are the
      only cells to express sustained levels of the Tbx6 and Lhx3 activators. Like
      mammalian Lhx3 genes, Ci-Lhx3 encodes two isoforms with distinct N-terminal
      peptides. The Lhx3a isoform appears to be expressed both maternally and
      zygotically, while the Lhx3b isoform is exclusively zygotic. Misexpression of
      Lhx3b is sufficient to induce ectopic Mesp activation in cells expressing Tbx6b.
      Injection of antisense morpholino oligonucleotides showed that the Lhx3b isoform
      is required for endogenous Mesp expression. Mutations in the Lhx3 half-site of
      Tbx6/Lhx3 composite elements strongly reduced the activity of a minimal Mesp
      enhancer. We discuss the delineation of the heart field by the synergistic action
      of muscle and gut determinants.

PMID- 19389356
TI  - The anchor cell initiates dorsal lumen formation during C. elegans vulval
      tubulogenesis.
AB  - Tubulogenesis and lumen formation are critical to the development of most organs.
      We study Caenorhabditis elegans vulval and uterine development to probe the
      complex mechanisms that mediate these events. Development of the vulva and the
      ventral uterus is coordinated by the inductive cell-signaling activity of a
      gonadal cell called the anchor cell (AC). We demonstrate that in addition to its
      function in specifying fate, the AC directly promotes dorsal vulval
      tubulogenesis. Two types of mutants with defective anchor cell behavior reveal
      that anchor cell invasion of the vulva is important for forming the toroidal
      shape of the dorsal vulval cell, vulF. In fos-1 mutants, where the AC cannot
      breakdown the basement membranes between the gonad and the vulva, and in mutants
      in unc-6 netrin or its receptor unc-40, which cause AC migration defects, the AC
      fails to invade the vulva and no lumen is formed in vulF. By examining GFP
      markers of dorsal vulval cell fate, we demonstrate that fate specification
      defects do not account for the aberrant vulF shape. We propose that the presence
      of the AC in the center of the developing vulF toroid is required for dorsal
      vulval lumen formation to complete vulval tubulogenesis.

PMID- 19389355
TI  - Retinoic acid receptors are required for skeletal growth, matrix homeostasis and
      growth plate function in postnatal mouse.
AB  - The retinoic acid receptors alpha, beta and gamma (RARalpha, RARbeta and
      RARgamma) are nuclear hormone receptors that regulate fundamental processes
      during embryogenesis, but their roles in skeletal development and growth remain
      unclear. To study skeletal-specific RAR function, we created conditional mouse
      mutants deficient in RAR expression in cartilage. We find that mice deficient in
      RARalpha and RARgamma (or RARbeta and RARgamma) exhibit severe growth retardation
      obvious by about 3 weeks postnatally. Their growth plates are defective and,
      importantly, display a major drop in aggrecan expression and content. Mice
      deficient in RARalpha and RARbeta, however, are virtually normal, suggesting that
      RARgamma is essential. In good correlation, we find that RARgamma is the most
      strongly expressed RAR in mouse growth plate and its expression characterizes the
      proliferative and pre-hypertrophic zones where aggrecan is strongly expressed
      also. By being avascular, those zones lack endogenous retinoids as indicated by
      previous RARE reporter mice and our direct biochemical measurements and thus,
      RARgamma is likely to exert ligand-less repressor function. Indeed, our data
      indicate that: aggrecan production is enhanced by RARgamma over-expression in
      chondrocytes under retinoid-free culture conditions; production is further
      boosted by co-repressor Zac1 or pharmacologic agents that enhance RAR repressor
      function; and RAR/Zac1 function on aggrecan expression may involve Sox proteins.
      In sum, our data reveal that RARs, and RARgamma in particular, exert previously
      unappreciated roles in growth plate function and skeletal growth and regulate
      aggrecan expression and content. Since aggrecan is critical for growth plate
      function, its deficiency in RAR-mutant mice is likely to have contributed
      directly to their growth retardation.

PMID- 19389358
TI  - Adult stem cell plasticity: neoblast repopulation in non-lethally irradiated
      planarians.
AB  - Planarians are a model system for studying adult stem cells, as they possess the
      neoblasts, a population of pluripotent adult stem cells able to give rise to both
      somatic and germ cells. Although over the last years several efforts have been
      made to shed light on neoblast biology, only recent evidence indicate that this
      population of cells is heterogeneous. In this study we irradiated planarians with
      different non-lethal X-ray doses (1-5 Gy) and we identified subpopulations of
      neoblasts with diverse levels of tolerance to X-rays. We demonstrated that a
      dramatic reduction of neoblasts occurred soon after non-lethal irradiations and
      that de-novo proliferation of some radioresistant cells re-established the
      primary neoblast number. In particular, a strong proliferation activity occurred
      at the ventral side of irradiated animals close to the nervous system. The
      produced cells migrated towards the dorsal parenchyma and, together with some
      dorsal radioresistant cells, reconstituted the entire neoblast population
      demonstrating the extreme plasticity of this adult stem cell system.

PMID- 19389359
TI  - Early onset of craniosynostosis in an Apert mouse model reveals critical features
      of this pathology.
AB  - Activating mutations of FGFRs1-3 cause craniosynostosis (CS), the premature
      fusion of cranial bones, in man and mouse. The mechanisms by which such mutations
      lead to CS have been variously ascribed to increased osteoblast proliferation,
      differentiation, and apoptosis, but it is not always clear how these disturbances
      relate to the process of suture fusion. We have reassessed coronal suture fusion
      in an Apert Fgfr2 (S252W) mouse model. We find that the critical event of CS is
      the early loss of basal sutural mesenchyme as the osteogenic fronts, expressing
      activated Fgfr2, unite to form a contiguous skeletogenic membrane. A mild
      increase in osteoprogenitor proliferation precedes but does not accompany this
      event, and apoptosis is insignificant. On the other hand, the more apical coronal
      suture initially forms appropriately but then undergoes fusion, albeit at a
      slower rate, accompanied by a significant decrease in osteoprogenitor
      proliferation, and increased osteoblast maturation. Apoptosis now accompanies
      fusion, but is restricted to bone fronts in contact with one another. We
      correlated these in vivo observations with the intrinsic effects of the activated
      Fgfr2 S252W mutation in primary osteoblasts in culture, which show an increased
      capacity for both proliferation and differentiation. Our studies suggest that the
      major determinant of Fgfr2-induced craniosynostosis is the failure to respond to
      signals that would halt the recruitment or the advancement of osteoprogenitor
      cells at the sites where sutures should normally form.

PMID- 19389360
TI  - CWN-1 functions with DSH-2 to regulate C. elegans asymmetric neuroblast division
      in a beta-catenin independent Wnt pathway.
AB  - In Caenorhabditis elegans, Wnt signaling regulates many asymmetric cell
      divisions. During embryogenesis, the C. elegans Dishevelled (Dsh) homolog, DSH-2,
      regulates asymmetric neuroblast division of the ABpl/rpppa blast cell. Dsh is a
      key intracellular component of both beta-catenin dependent and beta-catenin
      independent Wnt pathways. In C. elegans, most of the well-characterized
      asymmetric cell divisions regulated by Wnts are dependent on beta-catenin. In the
      ABpl/rpppa neuroblast division, however, we determined that DSH-2 regulates cell
      polarity through a beta-catenin independent Wnt pathway. We also established that
      the C. elegans Wnt homolog, cwn-1, functions to regulate asymmetric division of
      the ABpl/rpppa blast cell. Our results indicated that cwn-1 does not act alone in
      this process, and it functions with another redundant ligand that appears not to
      be a Wnt. Finally, we show widespread requirements for DSH-2 during embryogenesis
      in the generation of many other neurons. In particular, DSH-2 function is
      necessary for the correct production of the embryonic ventral cord motor neurons.
      This study demonstrates a role for DSH-2 and Wnt signaling in neuronal
      specification during C. elegans embryogenesis.

PMID- 19389361
TI  - Chordin is required for neural but not axial development in sea urchin embryos.
AB  - The oral-aboral (OA) axis in the sea urchin is specified by the TGFbeta family
      members Nodal and BMP2/4. Nodal promotes oral specification, whereas BMP2/4,
      despite being expressed in the oral territory, is required for aboral
      specification. This study explores the role of Chordin (Chd) during sea urchin
      embryogenesis. Chd is a secreted BMP inhibitor that plays an important role in
      axial and neural specification and patterning in Drosophila and vertebrate
      embryos. In Lytechinus variegatus embryos, Chd and BMP2/4 are functionally
      antagonistic. Both are expressed in overlapping domains in the oral territory
      prior to and during gastrulation. Perturbation shows that, surprisingly, Chd is
      not involved in OA axis specification. Instead, Chd is required both for normal
      patterning of the ciliary band at the OA boundary and for development of
      synaptotagmin B-positive (synB) neurons in a manner that is reciprocal with
      BMP2/4. Chd expression and synB-positive neural development are both downstream
      from p38 MAPK and Nodal, but not Goosecoid. These data are summarized in a model
      for synB neural development.

PMID- 19389362
TI  - Bicaudal-C associates with a Trailer Hitch/Me31B complex and is required for
      efficient Gurken secretion.
AB  - Bicaudal-C (Bic-C) is a multiple KH-domain RNA-binding protein required for
      Drosophila oogenesis and, maternally, for embryonic patterning. In early
      oogenesis, Bic-C negatively regulates target mRNAs, including Bic-C, by
      recruiting the CCR4 deadenylase through a direct association with its NOT3
      subunit. Here, we identify a novel function for Bic-C in secretion of the TGF
      alpha homolog Gurken (Grk). In Bic-C mutant egg chambers, Grk is sequestered
      within actin-coated structures during mid-oogenesis. As a consequence, Egfr
      signalling is not efficiently activated in the dorsal-anterior follicle cells.
      This phenotype is strikingly similar to that of trailer hitch (tral) mutants.
      Consistent with the idea that Bic-C and Tral act together in Grk secretion, Bic-C
      co-localizes with Tral within cytoplasmic granules, and can be co-purified with
      multiple protein components of a Tral mRNP complex. Taken together, our results
      implicate translational regulation by Bic-C and Tral in the secretory pathway.

PMID- 19389364
TI  - More constraint on ParaHox than Hox gene families in early metazoan evolution.
AB  - Hox and ParaHox (H/P) genes belong to evolutionary-sister clusters that arose
      through duplication of a ProtoHOX cluster early in animal evolution. In contrast
      to bilaterians, cnidarians express, beside PG1, PG2 and Gsx orthologs, numerous
      Hox-related genes with unclear origin. We characterized from marine hydrozoans
      three novel Hox-related genes expressed at medusa and polyp stages, which include
      a Pdx/Xlox ParaHox ortholog induced 1 day later than Gsx during embryonic
      development. To reconstruct H/P genes' early evolution, we performed multiple
      systematic comparative phylogenetic analyses, which identified derived sequences
      that blur the phylogenetic picture, recorded dramatically different evolutionary
      rates between ParaHox and Hox in cnidarians and showed the unexpected grouping of
      [Gsx-Pdx/Xlox-PG2-PG3] families in a single metagroup distinct from PG1. We
      propose a novel more parsimonious evolutionary scenario whereby H/P genes
      originated from a [Gsx-Pdx/Xlox-PG2-PG3]-related ProtoHox gene, the "posterior"
      and "anterior" H/P genes appearing secondarily. The ProtoHOX cluster would have
      contained the three Gsx/PG2, Pdx/PG3, Cdx/PG9 paralogs and produced through
      tandem duplication the primordial HOX and ParaHOX clusters in the Cnidaria
      Bilateria ancestor. The stronger constraint on cnidarian ParaHox genes suggests
      that the primary function of pre-bilaterian H/P genes was to drive cellular
      evolutionary novelties such as neurogenesis rather than axis specification.

PMID- 19389363
TI  - FGFR-1 is required by epicardium-derived cells for myocardial invasion and
      correct coronary vascular lineage differentiation.
AB  - Critical steps in coronary vascular formation include the epithelial-mesenchyme
      transition (EMT) that epicardial cells undergo to become sub-epicardial; the
      invasion of the myocardium; and the differentiation of coronary lineages.
      However, the factors controlling these processes are not completely understood.
      Epicardial and coronary vascular precursors migrate to the avascular heart tube
      during embryogenesis via the proepicardium (PE). Here, we show that in the quail
      embryo fibroblast growth factor receptor (FGFR)-1 is expressed in a spatially and
      temporally restricted manner in the PE and epicardium-derived cells, including
      vascular endothelial precursors, and is up-regulated in epicardial cells after
      EMT. We used replication-defective retroviral vectors to over-express or knock
      down FGFR-1 in the PE. FGFR-1 over-expression resulted in increased epicardial
      EMT. Knock-down of FGFR-1, however, did not inhibit epicardial EMT but greatly
      compromised the ability of PE progeny to invade the myocardium. The latter could,
      however, contribute to endothelia and smooth muscle of sub-epicardial vessels.
      Correct FGFR-1 levels were also important for correct coronary lineage
      differentiation with, at E12, an increase in the proportion of endothelial cells
      amongst FGFR-1 over-expressing PE progeny and a decrease in the proportion of
      smooth muscle cells in antisense FGFR-1 virus-infected PE progeny. Finally, in a
      heart explant system, constitutive activation of FGFR-1 signaling in epicardial
      cells resulted in increased delamination from the epicardium, invasion of the sub
      epicardium, and invasion of the myocardium. These data reveal novel roles for
      FGFR-1 signaling in epicardial biology and coronary vascular lineage
      differentiation, and point to potential new therapeutic avenues.

PMID- 19389366
TI  - Bmi-1 over-expression in neural stem/progenitor cells increases proliferation and
      neurogenesis in culture but has little effect on these functions in vivo.
AB  - The polycomb gene Bmi-1 is required for the self-renewal of stem cells from
      diverse tissues, including the central nervous system (CNS). Bmi-1 expression is
      elevated in most human gliomas, irrespective of grade, raising the question of
      whether Bmi-1 over-expression is sufficient to promote self-renewal or
      tumorigenesis by CNS stem/progenitor cells. To test this we generated Nestin-Bmi
      1-GFP transgenic mice. Analysis of two independent lines with expression in the
      fetal and adult CNS demonstrated that transgenic neural stem cells formed larger
      colonies, more self-renewing divisions, and more neurons in culture. However, in
      vivo, Bmi-1 over-expression had little effect on CNS stem cell frequency,
      subventricular zone proliferation, olfactory bulb neurogenesis, or
      neurogenesis/gliogenesis during development. Bmi-1 transgenic mice were born with
      enlarged lateral ventricles and a minority developed idiopathic hydrocephalus as
      adults, but none of the transgenic mice formed detectable CNS tumors, even when
      aged. The more pronounced effects of Bmi-1 over-expression in culture were
      largely attributable to the attenuated induction of p16(Ink4a) and p19(Arf) in
      culture, proteins that are generally not expressed by neural stem/progenitor
      cells in young mice in vivo. Bmi-1 over-expression therefore has more pronounced
      effects in culture and does not appear to be sufficient to induce tumorigenesis
      in vivo.

PMID- 19389367
TI  - Early thyroid development requires a Tbx1-Fgf8 pathway.
AB  - The thyroid develops within the pharyngeal apparatus from endodermally-derived
      cells. The many derivatives of the pharyngeal apparatus develop at similar times
      and sometimes from common cell types, explaining why many syndromic disorders
      express multiple birth defects affecting different structures that share a common
      pharyngeal origin. Thus, different derivatives may share common genetic networks
      during their development. Tbx1, the major gene associated with DiGeorge syndrome,
      is a key player in the global development of the pharyngeal apparatus, being
      required for virtually all its derivatives, including the thyroid. Here we show
      that Tbx1 regulates the size of the early thyroid primordium through its
      expression in the adjacent mesoderm. Because Tbx1 regulates the expression of
      Fgf8 in the mesoderm, we postulated that Fgf8 mediates critical Tbx1-dependent
      interactions between mesodermal cells and endodermal thyrocyte progenitors.
      Indeed, conditional ablation of Fgf8 in Tbx1-expressing cells caused an early
      thyroid phenotype similar to that of Tbx1 mutant mice. In addition, expression of
      an Fgf8 cDNA in the Tbx1 domain rescued the early size defect of the thyroid
      primordium in Tbx1 mutants. Thus, we have established that a Tbx1->Fgf8 pathway
      in the pharyngeal mesoderm is a key size regulator of mammalian thyroid.

PMID- 19389368
TI  - Twisted gastrulation limits apoptosis in the distal region of the mandibular arch
      in mice.
AB  - The mandibular arch (BA1) is critical for craniofacial development. The distal
      region of BA1, which gives rise to most of the mandible, is dependent upon an
      optimal level of bone morphogenetic protein (BMP) signaling. BMP activity is
      modulated in the extracellular space by BMP-binding proteins such as Twisted
      gastrulation (TWSG1). Twsg1(-/-) mice have a spectrum of craniofacial phenotypes,
      including mandibular defects that range from micrognathia to agnathia. At E9.5,
      the distal region of the mutant BA1 was prematurely and variably fused with loss
      of distal markers eHand and Msx1. Expression of proximal markers Fgf8 and Barx1
      was expanded across the fused BA1. The expression of Bmp4 and Msx2 was preserved
      in the distal region, but shifted ventrally. While wild type embryos showed a
      gradient of BMP signaling with higher activity in the distal region of BA1, this
      gradient was disrupted and shifted ventrally in the mutants. Thus, loss of TWSG1
      results in disruption of the BMP4 gradient at the level of signaling activity as
      well as mRNA expression. Altered distribution of BMP signaling leads to a shift
      in gene expression and increase in apoptosis. The extent of apoptosis may account
      for the variable degree of mandibular defects in Twsg1 mutants.

PMID- 19389369
TI  - EcR-B1 and Usp nuclear hormone receptors regulate expression of the VM32E
      eggshell gene during Drosophila oogenesis.
AB  - Ecdysone signaling plays key roles in Drosophila oogenesis, as its activity is
      required at multiple steps during egg chamber maturation. Recently, its
      involvement has been reported on eggshell production by controlling chorion gene
      transcription and amplification. Here, we present evidence that ecdysone
      signaling also controls the expression of the eggshell gene VM32E, whose product
      is a component of vitelline membrane and endochorion layers. Specifically
      blocking the function of the different Ecdysone receptor (EcR) isoforms we
      demonstrate that EcR-B1 is responsible for ecdysone-mediated VM32E
      transcriptional regulation. Moreover, we show that the EcR partner Ultraspiracle
      (Usp) is also necessary for VM32E expression. By analyzing the activity of
      specific VM32E regulatory regions in usp(2) clones we identify the promoter
      region mediating ecdysone-dependent VM32E expression. By in vitro binding assay
      and site-directed mutagenesis we demonstrate that this region contains a Usp
      binding site necessary for VM32E regulation. Our results further support the
      crucial role of ecdysone signaling in controlling transcription of eggshell
      structural genes and suggest that the heterodimeric complex EcR-B1/Usp mediates
      the ecdysone-dependent VM32E transcriptional activation in the main body follicle
      cells.

PMID- 19389370
TI  - Jagged 1 is necessary for normal mouse lens formation.
AB  - In mammals, two spatially and temporally distinct waves of fiber cell
      differentiation are crucial steps for normal lens development. In between these
      phases, an anterior growth zone forms in which progenitor cells migrate
      circumferentially, terminally exit the cell cycle and initiate differentiation at
      the lens equator. Much remains unknown about the molecular pathways orchestrating
      these processes. Previously, the Notch signal transduction pathway was shown to
      be critical for anterior lens progenitor cell growth and differentiation.
      However, the ligand or ligand(s) that direct these events are unknown. Using
      conditional gene targeting, we show that Jagged1 is required for lens fiber cell
      genesis, particularly that of secondary fiber cells. In the absence of Jagged1,
      the anterior growth and equatorial transition zones fail to develop fully, with
      only a handful of differentiated fiber cells present at birth. Adult Jagged1
      conditional mutants completely lack lenses, along with severe anterior chamber
      deformities. Our data support the hypothesis that Jagged1-Notch signaling conveys
      a lateral inductive signal, which is indispensable for lens progenitor cell
      proliferation and differentiation.

PMID- 19389371
TI  - Focal reduction of alphaE-catenin causes premature differentiation and reduction
      of beta-catenin signaling during cortical development.
AB  - Cerebral cortical precursor cells reside in a neuroepithelial cell layer that
      regulates their proliferation and differentiation. Global disruptions in
      epithelial architecture induced by loss of the adherens junction component alphaE
      catenin lead to hyperproliferation. Here we show that cell autonomous reduction
      of alphaE-catenin in the background of normal precursors in vivo causes cells to
      prematurely exit the cell cycle, differentiate into neurons, and migrate to the
      cortical plate, while normal neighboring precursors are unaffected.
      Mechanistically, alphaE-catenin likely regulates cortical precursor
      differentiation by maintaining beta-catenin signaling, as reduction of alphaE
      catenin leads to reduction of beta-catenin signaling in vivo. These results
      demonstrate that, at the cellular level, alphaE-catenin serves to maintain
      precursors in the proliferative ventricular zone, and suggest an unexpected
      function for alphaE-catenin in preserving beta-catenin signaling during cortical
      development.

PMID- 19389372
TI  - The role of Wnt5a in prostate gland development.
AB  - The Wnt genes encode a large family of secreted glycoproteins that play important
      roles in controlling tissue patterning, cell fate and proliferation during
      development. Currently, little is known regarding the role(s) of Wnt genes during
      prostate gland development. The present study examines the role of the
      noncanonical Wnt5a during prostate gland development in rat and murine models. In
      the rat prostate, Wnt5a mRNA is expressed by distal mesenchyme during the budding
      stage and localizes to periductal mesenchymal cells with an increasing proximal
      to-distal gradient during branching morphogenesis. Wnt5a protein is secreted and
      localizes to periductal stroma, extracellular matrix and epithelial cells in the
      distal ducts. While Wnt5a expression is high during active morphogenesis in all
      prostate lobes, ventral prostate (VP) expression declines rapidly following
      morphogenesis while dorsal (DP) and lateral lobe (LP) expression remains high
      into adulthood. Steroids modulate prostatic Wnt5a expression during early
      development with testosterone suppressing Wnt5a and neonatal estrogen increasing
      expression. In vivo and ex vivo analyses of developing mouse and rat prostates
      were used to assess the functional roles of Wnt5a. Wnt5a(-/-) murine prostates
      rescued by organ culture exhibit disturbances in bud position and directed
      outgrowth leading to large bulbous sacs in place of elongating ducts. In
      contrast, epithelial cell proliferation, ductal elongation and branchpoint
      formation are suppressed in newborn rat prostates cultured with exogenous Wnt5a
      protein. While renal grafts of Wnt5a(-/-) murine prostates revealed that Wnt5a is
      not essential for cyto- and functional differentiation, a role in luminal cell
      polarity and lumenization of the ducts was indicated. Wnt5a suppresses prostatic
      Shh expression while Shh stimulates Wnt5a expression in a lobe-specific manner
      during early development indicating that Wnt5a participates in cross-talk with
      other members of the gene regulatory network that control prostate development.
      Although Wnt5a does not influence prostatic expression of other Wnt morphogens,
      it suppresses Wif-1 expression and can thus indirectly modulate Wnt signaling. In
      summary, the present finds demonstrate that Wnt5a is essential for normal
      prostate development where it regulates bud outgrowth, ductal elongation,
      branching, cell polarity and lumenization. These findings contribute to the
      growing body of knowledge on regulatory mechanisms involved in prostate gland
      development which are key to understanding abnormal growth processes associated
      with aging.

PMID- 19389373
TI  - Akt regulates skeletal development through GSK3, mTOR, and FoxOs.
AB  - Although Akt plays key roles in various cellular processes, the functions of Akt
      and Akt downstream signaling pathways in the cellular processes of skeletal
      development remain to be clarified. By analyzing transgenic embryos that
      expressed constitutively active Akt (myrAkt) or dominant-negative Akt in
      chondrocytes, we found that Akt positively regulated the four processes of
      chondrocyte maturation, chondrocyte proliferation, cartilage matrix production,
      and cell growth in skeletal development. As phosphorylation of GSK3beta, S6K, and
      FoxO3a was enhanced in the growth plates of myrAkt transgenic mice, we examined
      the Akt downstream signaling pathways by organ culture. The Akt-mTOR pathway was
      responsible for positive regulation of the four cellular processes. The Akt-FoxO
      pathway enhanced chondrocyte proliferation but inhibited chondrocyte maturation
      and cartilage matrix production, while the Akt-GSK3 pathway negatively regulated
      three of the cellular processes in limb skeletons but not in vertebrae due to
      less GSK3 expression in vertebrae. These findings indicate that Akt positively
      regulates the cellular processes of skeletal growth and endochondral
      ossification, that the Akt-mTOR, Akt-FoxO, and Akt-GSK3 pathways positively or
      negatively regulate the cellular processes, and that Akt exerts its function in
      skeletal development by tuning the three pathways in a manner dependent on the
      skeletal part.

PMID- 19389374
TI  - Trps1, a regulator of chondrocyte proliferation and differentiation, interacts
      with the activator form of Gli3.
AB  - Trps1, the gene mutated in human Tricho-Rhino-Phalangeal syndrome, represents an
      atypical member of the GATA-family of transcription factors. Here we show that
      Trps1 interacts with Indian hedgehog (Ihh)/Gli3 signaling and regulates
      chondrocyte differentiation and proliferation. We demonstrate that Trps1
      specifically binds to the transactivation domain of Gli3 in vitro and in vivo,
      whereas the repressor form of Gli3 does not interact with Trps1. A domain of
      185aa within Trps1, containing three predicted zinc fingers, is sufficient for
      interaction with Gli3. Using different mouse models we find that in distal
      chondrocytes Trps1 and the repressor activity of Gli3 are required to expand
      distal cells and locate the expression domain of Parathyroid hormone related
      peptide. In columnar proliferating chondrocytes Trps1 and Ihh/Gli3 have an
      activating function. The differentiation of columnar and hypertrophic
      chondrocytes is supported by Trps1 independent of Gli3. Trps1 seems thus to
      organize chondrocyte differentiation interacting with different subsets of co
      factors in distinct cell types.

PMID- 19389375
TI  - Functional equivalence of the zinc finger transcription factors Osr1 and Osr2 in
      mouse development.
AB  - Osr1 and Osr2 are the only mammalian homologs of the Drosophila odd-skipped
      family developmental regulators. The Osr1 protein contains three zinc-finger
      motifs whereas Osr2 exists in two isoforms, containing three and five zinc-finger
      motifs respectively, due to alternative splicing of the transcripts. Targeted
      null mutations in these genes in mice resulted in distinct phenotypes, with heart
      and urogenital developmental defects in Osr1(-/-) mice and with cleft palate and
      open eyelids at birth in Osr2(-/-) mice. To investigate whether these contrasting
      mutant phenotypes are due to differences in their protein structure or to
      differential expression patterns, we generated mice in which the endogenous Osr2
      coding region was replaced by either Osr1 cDNA or Osr2A cDNA encoding the five
      finger isoform. The knockin alleles recapitulated endogenous Osr2 mRNA expression
      patterns in most tissues and completely rescued cleft palate and cranial skeletal
      developmental defects of Osr2(-/-) mice. Mice hemizygous or homozygous for either
      knockin allele exhibited open-eyelids at birth, which correlated with differences
      in expression patterns between the knockin allele and the endogenous Osr2 gene
      during eyelid development. Molecular marker analyses in Osr2(-/-) and
      Osr2(Osr1ki/Osr1ki) mice revealed that Osr2 controls eyelid development through
      regulation of the Fgf10-Fgfr2 signaling pathway and that Osr1 rescued Osr2
      function in maintaining Fgf10 expression during eyelid development in
      Osr2(Osr1ki/Osr1ki) mice. These results indicate that the distinct functions of
      Osr1 and Osr2 during mouse development result from evolutionary divergence of
      their cis regulatory sequences rather than distinct biochemical activities of
      their protein products.

PMID- 19389376
TI  - Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression
      in the neural tube.
AB  - Delta-like 3 (Dll3) is a Delta family member expressed broadly in the developing
      nervous system as neural progenitor cells initiate differentiation. A proximal
      promoter sequence for Dll3 is conserved across multiple species and is sufficient
      to direct GFP expression in a Dll3-like pattern in the neural tube of transgenic
      mice. This promoter contains multiple E-boxes, the consensus binding site for
      bHLH factors. Dll3 expression and the activity of the Dll3-promoter in the dorsal
      neural tube depends on the basic helix-loop-helix (bHLH) transcription factors
      Ascl1 (Mash1) and Neurog2 (Ngn2). Mutations in each E-box identified in the Dll3
      promoter allowed distinct enhancer or repressor properties to be assigned to each
      site individually or in combination. In addition, each E-box has distinct
      characteristics relative to binding of bHLH factors Ascl1, Neurog1, and Neurog2.
      Surprisingly, novel Ascl1 containing DNA binding complexes are identified that
      interact with specific E-box sites within the Dll3-promoter in vitro. These
      complexes include Ascl1/Ascl1 homodimers and Ascl1/Neurog2 heterodimers,
      complexes that in some cases require additional undefined factors for efficient
      DNA binding. Thus, a complex interplay of E-box binding proteins spatially and
      temporally regulate Dll3 levels during neural tube development.

PMID- 19389377
TI  - Dll1 and Dll4 function sequentially in the retina and pV2 domain of the spinal
      cord to regulate neurogenesis and create cell diversity.
AB  - Signalling mediated by Notch receptors is known to have multiple functions during
      vertebrate neural development, regulating processes like progenitor
      differentiation and cell type diversification. Various Notch ligands are
      expressed in the developing nervous system and their activities might contribute
      to this multiplicity of functions. Here, we show that two Delta-like genes, Dll1
      and Dll4, are sequentially expressed in differentiating neurons of the embryonic
      mouse retina and spinal cord's pV2 domain, with Dll1 starting to be expressed
      before Dll4. Analysis of Dll1 mutants reveals this gene is necessary and
      sufficient to maintain a pool of progenitors in the embryonic neuroepithelium.
      Accordingly, in the spinal cord domains where Dll1 is the only expressed Notch
      ligand, its inactivation leads to an increased rate of neurogenesis and premature
      differentiation of neural progenitors. In contrast, in the pV2 domain and retina
      where Dll1 is co-expressed with Dll4, progenitors are not exhausted and cell
      diversity is maintained. Together, our results support a model where Dll1 and
      Dll4 are part of a unique genetic circuitry that regulates subsequent steps of
      neurogenesis in the retina and pV2 domain: while Dll1 serves to prevent the
      untimely differentiation of neural progenitors, Dll4 might function to generate
      diversity within the population of differentiating neurons.

PMID- 19389382
TI  - Role of matrix metalloproteinase-9 in lipopolysaccharide-induced mucin production
      in human airway epithelial cells.
AB  - Matrix metalloproteinases (MMPs) have been found to be involved in the
      pathogenesis of inflammatory airway diseases. However, the role of MMPs in
      lipopolysaccharide (LPS)-induced mucin overproduction remains unclear. We
      explored the role of MMP-9 in LPS-induced MUC5AC production and the effect of
      doxycycline on MUC5AC production. The study showed that LPS induced transcription
      and protein expression of both MMP-9 and MUC5AC in NCI-H292 cells and in primary
      human epithelial cells, and the increased MUC5AC level were associated with
      increased MMP-9 transcripts, protein and activity. However, the increase of
      MUC5AC transcripts and protein were diminished after cells had been treated with
      doxycycline, MMP-9 siRNA or EGFR inhibitor. Doxycycline inhibited MMP-9
      transcription, protein production and activity, while LPS-induced increase of MMP
      9 transcription was inhibited by EGFR inhibitor, p38 MAPK and JNK inhibitor. The
      LPS-induced phosphorylation of p38 MAPK and JNK were inhibited by EGFR inhibitor.
      These results suggested that LPS-induced MUC5AC production may be partially
      mediated by MMP-9 activation and EGFR-p38 MAPK/JNK signaling pathway. Doxycycline
      may play a therapeutic role in LPS-induced mucus hypersecretion.

PMID- 19389383
TI  - Construction and engineering of a thermostable self-sufficient cytochrome P450.
AB  - CYP175A1 is a thermophilic cytochrome P450 and hydroxylates beta-carotene. We
      previously identified a native electron transport system for CYP175A1. In this
      report, we constructed two fusion proteins consisting of CYP175A1, ferredoxin
      (Fdx), and ferredoxin-NADP(+) reductase (FNR): H(2)N-CYP175A1-Fdx-FNR-COOH
      (175FR) and H(2)N-CYP175A1-FNR-Fdx-COOH (175RF). Both 175FR and 175RF were
      expressed in Escherichia coli and purified. The V(max) value for beta-carotene
      hydroxylation was 25 times higher with 175RF than 175FR and 9 times higher with
      175RF than CYP175A1 (non-fused protein), although the k(m) values of these
      enzymes were similar. 175RF retained 50% residual activity even at 80 degrees C.
      Furthermore, several mutants of the CYP175A1 domain of 175RF were prepared and
      one mutant (Q67G/Y68I) catalyzed the hydroxylation of an unnatural substrate,
      testosterone. Thus, this is the first report of a thermostable self-sufficient
      cytochrome P450 and the engineering of a thermophilic cytochrome P450 for the
      oxidation of an unnatural substrate.

PMID- 19389384
TI  - Identification of aspartic acid-203 in human thymidine phosphorylase as an
      important residue for both catalysis and non-competitive inhibition by the small
      molecule "crystallization chaperone" 5'-O-tritylinosine (KIN59).
AB  - Thymidine phosphorylase (TP) is a catabolic enzyme in thymidine metabolism that
      is frequently upregulated in many solid tumors. Elevated TP levels are associated
      with tumor angiogenesis, metastasis and poor prognosis. Therefore, the use of TP
      inhibitors might offer a promising strategy for cancer treatment. The tritylated
      inosine derivative 5'-O-tritylinosine (previously designated KIN59) is a non
      competitive inhibitor of TP which was previously found to be instrumental for the
      crystallization of human TP. A combination of computational studies including
      normal mode analysis, automated ligand docking and molecular dynamics simulations
      were performed to define a plausible binding site for 5'-O-tritylinosine on human
      TP. A cavity in which 5'-O-tritylinosine could fit was identified in the vicinity
      of the Gly405-Val419 loop at a distance of about 11A from the substrate-binding
      site. In the X-ray crystal structure, this pocket is characterized by an
      intricate hydrogen-bonding network in which Asp203 was found to play an important
      role to afford the loop stabilization that is required for efficient enzyme
      catalysis. Site-directed mutagenesis of this amino acid residue afforded a mutant
      enzyme with a severely compromised catalytic efficiency (V(max)/K(m) of mutant
      enzyme approximately 50-fold lower than for wild-type TP) and pronounced
      resistance to the inhibitory effect of 5'-O-tritylinosine. In contrast, the D203A
      mutant enzyme kept full sensitivity to the competitive inhibitors 6-aminothymine
      and 6-amino-5-bromouracil, which is in line with the kinetic properties of these
      inhibitors. Our findings reveal the existence of a previously unrecognized site
      in TP that can be targeted by small molecules to inhibit the catalytic activity
      of TP.

PMID- 19389385
TI  - Oversulfated chondroitin sulfate interaction with heparin-binding proteins: new
      insights into adverse reactions from contaminated heparins.
AB  - An oversulfated chondroitin sulfate (OSCS) was identified as a contaminant to
      pharmaceutical heparin and severe anaphylactoid reactions were ascribed to this
      contaminant. An examination of the biochemistry underlying both the anticoagulant
      activity and the toxic effects of oversulfated chondroitin sulfate was
      undertaken. This study demonstrates that the anticoagulant activity of this
      oversulfated chondroitin sulfate is primarily dependent on heparin cofactor II
      mediated inhibition of thrombin. Heparin and oversulfated chondroitin sulfate
      binding to coagulation, kinin-kallikrein and complement proteins were studied by
      surface plasmon resonance. While oversulfated chondroitin sulfate binds tightly
      to antithrombin III, unlike heparin, OSCS does not induce antithrombin III to
      undergo the conformational change required for its inactivation of thrombin and
      factor Xa. In contrast to heparin, oversulfated chondroitin sulfate tightly binds
      factor XIIa suggesting a biochemical mechanism for the factor XIIa-based
      enhancement of vasoactive bradykinin production.

PMID- 19389386
TI  - Separate influences in learning: evidence from artificial grammar learning with
      traumatic brain injury patients.
AB  - Artificial grammar learning (AGL) is one of the most extensively employed
      paradigms for the study of learning. Grammaticality is one of the most common
      ways to index performance in AGL. However, there is still extensive debate on
      whether there is a distinct psychological process which can lead to
      grammaticality knowledge. An application of the COVIS model of categorization in
      AGL suggests that grammaticality might arise from a hypothesis-testing system
      (when grammaticality is appropriately balanced with other knowledge influences),
      so that prefrontal cortex damage should be associated with impaired
      grammaticality and intact chunk strength performance. This prediction was
      confirmed in a study of traumatic brain injury (TBI) patients and matched
      controls. The TBI patient cohort had diffuse prefrontal cortex damage as
      evidenced by the history of their injury, CT scans, and severe executive
      functioning problems. Our results allow a novel interpretation of grammaticality
      and AGL in general.

PMID- 19389387
TI  - Effects of GDNF pretreatment on function and survival of transplanted fetal
      ventral mesencephalic cells in the 6-OHDA rat model of Parkinson's disease.
AB  - Transplantation of fetal dopaminergic (DA) neurons offers an experimental therapy
      for Parkinson's disease (PD). The low availability and the poor survival and
      integration of transplanted cells in the host brain are major obstacles in this
      approach. Glial cell line-derived neurotrophic factor (GDNF) is a potent
      neurotrophic factor with growth- and survival-promoting capabilities for
      developing DA neurons. In the present study, we examined whether pretreatment of
      ventral mesencephalic (VM) free-floating roller tube (FFRT) cultures with GDNF
      would improve graft survival and function. For that purpose organotypic cultures
      of E14 rat VM were grown for 2, 4 or 8 days in the absence (control) or presence
      of GDNF [10 ng/ml] and transplanted into the striatum of 6-hydroxydopamine
      lesioned rats. While all groups of rats showed a significant reduction in d
      amphetamine-induced rotations at 6 weeks posttransplantation a significantly
      improved graft function was observed only in the days in vitro (DIV) 4 GDNF
      pretreated group compared to the control group. In addition, no statistical
      significant differences between groups were found in the number of surviving
      tyrosine hydroxylase-immunoreactive (TH-ir) neurons assessed at 9 weeks
      posttransplantation. However, a tendency for higher TH-ir fiber outgrowth from
      the transplants in the GDNF pretreated groups as compared to corresponding
      controls was observed. Furthermore, GDNF pretreatment showed a tendency for a
      higher number of GIRK2 positive neurons in the grafts. In sum, our findings
      demonstrate that GDNF pretreatment was not disadvantageous for transplants of
      embryonic rat VM with the FFRT culture technique but only marginally improved
      graft survival and function.

PMID- 19389389
TI  - Effects of electrical and chemical stimulation of the amygdala on the spontaneous
      discharge in the insular cortex in rats.
AB  - Both the amygdala (especially, the basolateral nucleus of the amygdala) and the
      insular cortex are important for conditioned taste aversion. From the anatomical
      view point, there are reciprocal connections between the insular cortex and the
      amygdala. In the present study, we investigated the effect of electrical and
      chemical stimulation of the amygdala on the spontaneous discharge of the insular
      cortex neurons in anesthetized rats. In most neurons (10 of 14), spontaneous
      discharge was decreased after a microinjection of glutamate (Glu). In these
      neurons, the injection site was within the basolateral nucleus of the amygdala
      (the basolateral/lateral nuclei). On the other hand, when a gamma amino-butyric
      acid (GABA) was microinjected into the basolateral nucleus of the amygdala, none
      of the 5 neurons showed any change in spontaneous discharge. Electrical train
      stimulation of the basolateral nucleus of the amygdala (100 Hz, 2-6 s) depressed
      the spontaneous discharge of the neurons in the insular cortex, as in the case of
      a Glu microinjection. These results indicate that activation of the basolateral
      nucleus of the amygdala could depress the neuronal activity in the insular
      cortex. Such results may yield data leading to the elucidation of the neuronal
      mechanisms of conditioned taste aversion.

PMID- 19389388
TI  - Estrogen attenuates glutamate-induced cell death by inhibiting Ca2+ influx
      through L-type voltage-gated Ca2+ channels.
AB  - Estrogen-mediated neuroprotection is observed in neurodegenerative disease and
      neurotrauma models; however, determining a mechanism for these effects has been
      difficult. We propose that estrogen may limit cell death in the nervous system
      tissue by inhibiting increases in intracellular free Ca(2+). Here, we present
      data using VSC 4.1 cell line, a ventral spinal motoneuron and neuroblastoma
      hybrid cell line. Treatment with 1 mM glutamate for 24 h induced apoptosis. When
      cells were pre-treated with 100 nM 17beta-estradiol (estrogen) for 1 h and then
      co-treated with glutamate, apoptotic death was significantly attenuated. Estrogen
      also prevented glutamate-mediated changes in resting membrane potential and
      membrane capacitance. Treatment with either 17 alpha-estradiol or cell
      impermeable estrogen did not mimic the findings seen with estrogen. Glutamate
      treatment significantly increased both intracellular free Ca(2+) and the
      activities of downstream proteases such as calpain and caspase-3. Estrogen
      attenuated both the increases in intracellular free Ca(2+) and protease
      activities. In order to determine the pathway responsible for estrogen-mediated
      inhibition of these increases in intracellular free Ca(2+), cells were treated
      with several Ca(2+) entry inhibitors, but only the L-type Ca(2+) channel blocker
      nifedipine demonstrated cytoprotective effects comparable to estrogen. To expand
      these findings, cells were treated with the L-type Ca(2+) channel agonist FPL
      64176, which increased both cell death and intracellular free Ca(2+), and
      estrogen inhibited both effects. From these observations, we conclude that
      estrogen limits glutamate-induced cell death in VSC 4.1 cells through effects on
      L-type Ca(2+) channels, inhibiting Ca(2+) influx as well as activation of the pro
      apoptotic proteases calpain and caspase-3.

PMID- 19389390
TI  - Biochip arrays for the discovery of a biomarker surrogate in a phase I/II study
      assessing a novel anti-metastasis agent.
AB  - OBJECTIVE: Can biochip arrays identify which individuals with metastatic disease
      will respond to an anti-metastatic agent? DESIGN AND METHODS: Cytokine and cell
      adhesion arrays (Randox Ltd) were measured over 1 month in 9 research
      participants receiving CTCE-9908 in a Phase I/II study. RESULTS: Research
      participants with stable disease (n=2) had significantly higher soluble VCAM-1 as
      compared to those that progressed. DISCUSSION: VCAM-1 measurement early during
      CTCE-9908 treatment might be used as a surrogate for response.

PMID- 19389391
TI  - Increased circulating Dickkopf-1 in Paget's disease of bone.
AB  - Dickkopf-1 (Dkk-1) is a secreted inhibitor of Wnt signaling which in adults
      regulates bone turnover. Dkk-1 over-production is implicated in osteolytic
      disease where it inhibits bone formation and stimulates bone breakdown. Recently
      it was reported that osteoblastic cells from Paget's disease of bone (PDB) over
      expressed Dkk-1. OBJECTIVE: To see if increased Dkk-1 was detected in serum from
      patients with PDB. RESULTS: Dkk-1 and total serum alkaline phosphatase activity
      (tsAP) were significantly elevated in sera from PDB patients. Patients with
      polyostotic PDB had significantly higher levels of tsAP but not Dkk-1, than
      monostotic patients. TsAP but not Dkk-1, was significantly lower in sera from
      bisphosphonate treated versus untreated PDB patients. Dkk-1 and tsAP were not
      significantly correlated. CONCLUSIONS: Dkk-1 may be a useful biomarker of PDB and
      we speculate that Dkk-1 may play a central role in the etiology of PDB.

PMID- 19389392
TI  - Unexpected functional redundancy between Twist and Slug (Snail2) and their
      feedback regulation of NF-kappaB via Nodal and Cerberus.
AB  - A NF-kappaB-Twist-Snail network controls axis and mesoderm formation in
      Drosophila. Using translation-blocking morpholinos and hormone-regulated
      proteins, we demonstrate the presence of an analogous network in the early
      Xenopus embryo. Loss of twist (twist1) function leads to a reduction of mesoderm
      and neural crest markers, an increase in apoptosis, and a decrease in snail1
      (snail) and snail2 (slug) mRNA levels. Injection of snail2 mRNA rescues twist's
      loss of function phenotypes and visa versa. In the early embryo NF-kappaB/RelA
      regulates twist, snail2, and snail1 mRNA levels; similarly Nodal/Smad2 regulate
      twist, snail2, snail1, and relA RNA levels. Both Twist and Snail2 negatively
      regulate levels of cerberus RNA, which encodes a Nodal, bone morphogenic protein
      (BMP), and Wnt inhibitor. Cerberus's anti-Nodal activity inhibits NF-kappaB
      activity and decreases relA RNA levels. These results reveal both conserved and
      unexpected regulatory interactions at the core of a vertebrate's mesodermal
      specification network.

PMID- 19389393
TI  - Effects of silodosin and tamsulosin on the urethra and cardiovascular system in
      young and old dogs with benign prostatic hyperplasia.
AB  - We examined whether the effects (efficacy on the urethra and hypotension) of
      silodosin (alpha(1A)-adrenoceptor antagonist) and tamsulosin (alpha(1A+1D)
      adrenoceptor antagonist) in dogs with benign prostatic hyperplasia altered with
      age. We used young and old dogs, diagnosed as having benign prostatic hyperplasia
      by veterinarian's palpation. Under anesthesia, the increase in intraurethral
      pressure evoked by hypogastric nerve stimulation was measured, together with the
      level of systemic mean blood pressure. Each drug was administered intravenously
      in progressively increasing doses. At the end of the experiment, the prostate was
      isolated from each dog, then weighed and investigated pathologically to confirm
      benign prostatic hyperplasia. The wet weight of the prostate was greater in old
      dogs with benign prostatic hyperplasia than in young dogs with benign prostatic
      hyperplasia. By light microscopy, hyperplasia in the prostatic epithelium was
      confirmed in both groups. Silodosin (0.3-300 microg/kg) dose-dependently
      inhibited the hypogastric nerve stimulation-induced increase in intraurethral
      pressure (without significant hypotensive effects) in both young and old dogs
      with benign prostatic hyperplasia. Tamsulosin (0.3-300 microg/kg) also dose
      dependently inhibited the intraurethral pressure increase in both groups, but it
      had a hypotensive effect that was significantly greater in old than in young dogs
      with benign prostatic hyperplasia. In conclusion, as regards the effect of
      silodosin on intraurethral pressure, potency was similar between young and old
      dogs with benign prostatic hyperplasia, and it was without significant
      hypotensive effects. We therefore suggest that silodosin might be a good
      medication for lower urinary tract symptoms in patients with benign prostatic
      hyperplasia in all age groups.

PMID- 19389394
TI  - Endostar, a modified endostatin inhibits non small cell lung cancer cell in vitro
      invasion through osteopontin-related mechanism.
AB  - In this study, we studied the inhibition of non small cell lung cancer (NSCLC)
      cells invasion by a recombinant human Endostar, a modified endostatin and the
      possible osteopontin-related mechanism. The results showed that Endostar
      significantly inhibited highly metastatic NSCLC (NCI-H460) cells in vitro
      invasion. ELISA demonstrated that reduction of osteopontin level in the medium by
      Endostar may be responsible for the inhibition of invasion. RT-PCR assay and
      western blot analysis revealed that the reduction of osteopontin was due to under
      regulation of osteopontin expression. Furthermore, Endostar also inhibited
      osteopontin-induced less metastatic NSCLC (A549) cells invasion, indicating that
      Endostar may have other different osteopontin-related mechanism. In an adhesion
      assay, we found that Endostar reduced NCI-H460 cells binding to osteopontin. Flow
      cytometric analysis suggested that the reduction of adhesion may be related to
      under-regulation of its receptors (CD44v6 and alpha(V)beta(3) integrin)
      expression. Additionally, we found, via gelatin zymographic analysis, that
      osteopontin-induced the expression and activation of pro-matrix metalloproteinase
      (MMP)-2 and pro MMP-9 secreted from A549 cells were blocked upon Endostar
      treatment, indicating that Endostar may block osteopontin-mediated signal
      transduction pathways through MMP families. The above results indicate that
      Endostar may have an intrinsic non-angiogenesis-related antitumor activity
      through osteopontin-related mechanism against NSCLC, including osteopontin change
      and osteopontin signal transduction blockade. Tumor cell invasion is important
      for tumor metastasis, our findings suggest that it is probably a good strategy to
      put Endostar into treatment of NSCLC metastasis.

PMID- 19389395
TI  - alpha(2)-Adrenoceptor agonist xylazine induces peripheral antinociceptive effect
      by activation of the L-arginine/nitric oxide/cyclic GMP pathway in rat.
AB  - The L-arginine/nitric oxide/cyclic GMP pathway has been proposed as the mechanism
      of action for peripheral antinociception concerning several groups of drugs,
      including opioids and nonsteroidal analgesics. The aim of the present study was
      to investigate the involvement of the L-arginine/NO/cGMP pathway on
      antinociception induced by xylazine, an alpha(2)-adrenoceptor agonist extensively
      used in veterinary medicine and animal experimentation. The rat paw pressure test
      was used by inducing hyperalgesia via intraplantar injection of prostaglandin
      E(2) (2 microg). Xylazine was administered locally into the right hind paw (25,
      50 and 100 microg) and either NO synthase inhibitor L-NOarg (12, 18 and 24
      microg/paw), soluble guanylyl cyclase inhibitor ODQ (25, 50 and 100 microg/paw)
      or cGMP-phosphodiesterase inhibitor zaprinast (50 microg/paw) were previously
      administered to the right hind paw of Wistar rats. Xylazine administration
      elicited a local antinociceptive effect, since only much higher doses produce a
      systemic effect in the contralateral paw. The peripheral antinociceptive effect
      induced by xylazine (100 microg/paw) was antagonized by L-NOarg and by ODQ;
      however, zaprinast potentiated the antinociceptive effect of xylazine at 25
      microg/paw. The results provide evidence that xylazine probably induces
      peripheral antinociceptive effect by L-arginine/NO/cGMP pathway activation.

PMID- 19389396
TI  - A specific isoform of poly(ADP-ribose) glycohydrolase is targeted to the
      mitochondrial matrix by a N-terminal mitochondrial targeting sequence.
AB  - Poly(ADP-ribose) polymerases (PARPs) convert NAD to polymers of ADP-ribose that
      are converted to free ADP-ribose by poly(ADP-ribose) glycohydrolase (PARG). The
      activation of the nuclear enzyme PARP-1 following genotoxic stress has been
      linked to release of apoptosis inducing factor from the mitochondria, but the
      mechanisms by which signals are transmitted between nuclear and mitochondrial
      compartments are not well understood. The study reported here has examined the
      relationship between PARG and mitochondria in HeLa cells. Endogenous PARG
      associated with the mitochondrial fraction migrated in the range of 60 kDa.
      Transient transfection of cells with PARG expression constructs with amino acids
      encoded by exon 4 at the N-terminus was targeted to the mitochondria as
      demonstrated by subcellular fractionation and immunofluorescence microscopy of
      whole cells. Deletion and missense mutants allowed identification of a canonical
      N-terminal mitochondrial targeting sequence consisting of the first 16 amino
      acids encoded by PARG exon 4. Sub-mitochondrial localization experiments indicate
      that this mitochondrial PARG isoform is targeted to the mitochondrial matrix. The
      identification of a PARG isoform as a component of the mitochondrial matrix
      raises several interesting possibilities concerning mechanisms of nuclear
      mitochondrial cross talk involved in regulation of cell death pathways.

PMID- 19389397
TI  - Carbohydrate analysis of Acanthamoeba castellanii.
AB  - We analyzed biochemically Acanthamoeba castellanii trophozoites, intact cysts and
      cyst walls belonging to the T4 genotype using gas chromatography combined with
      mass spectrometry. Cyst walls were prepared by removing intracellular material
      from cysts by pre-treating them with sodium dodecyl sulphate (SDS) containing
      dithiothreitol, and then subjecting these to a series of sequential enzymatic
      digestions using amyloglucosidase, papain, DNase, RNase and proteinase K. The
      resulting "cyst wall" material was subsequently lyophilized and subjected to
      glycosyl composition analysis. Transmission electron microscopy confirmed the
      removal of intracystic material following enzymatic treatment. Our results showed
      that treated A. castellanii trophozoites, intact cysts and cyst walls contained
      various sugar moieties, of which a high percentage was galactose and glucose, in
      addition to small amounts of mannose, and xylose. Linkage analysis revealed
      several types of glycosidic linkages including the 1,4-linked glucosyl
      conformation, indicative of cellulose. Inhibitor studies suggested that, beside
      sugar synthesis, cytoskeletal re-arrangement and mitogen-activated protein kinase
      mediated pathways are involved in A. castellanii encystment.

PMID- 19389398
TI  - Trypanosoma cruzi: new insights on ecophylogeny and hybridization by multigene
      sequencing of three nuclear and one maxicircle genes.
AB  - Natural populations of Trypanosoma cruzi are structured into five genetic
      lineages, T. cruzi I and T. cruzi II a to e, as the result of clonal evolution
      with rare genetic recombination events. To explore more in depth these
      phenomenons, a multigene sequencing approach was used, for the first time in the
      case of T. cruzi. Three nuclear loci and a maxicircle locus were sequenced on 18
      T. cruzi stocks. Sequences were used to build phylogenetic trees from each locus
      and from concatenated sequences of all loci. The data confirmed the hybrid origin
      of DTUs IId and IIe, as the result of an ancient genetic recombination between
      strains pertaining to IIb and IIc. The data confirmed also a hybrid origin of
      DTUs IIa and IIc. Contrary to previous reports, we failed to detect mosaic genes.
      The phylogenetic relationship between DTUs and the respective roles of
      recombination and selection were tested.

PMID- 19389399
TI  - Schistosoma mansoni: effect of dietary zinc supplement on egg granuloma in Swiss
      mice treated with praziqantel.
AB  - Schistosomiasis is one of the most important parasitic diseases in Egypt and
      chemotherapy is considered the most effective method of control. This study was
      conducted to assess the effectiveness of zinc administration against Schistosoma
      mansoni infection by evaluating the activities of arylesterase and paraoxonase
      (PON1) enzymes, and the degree of liver damage. One hundred and twenty albino
      mice were divided into two groups; one was an infected control and the other a
      treated group which was further subdivided into three according to the
      praziquantel and zinc supplementation given. Blood and liver samples, collected
      10 weeks post-infection, were subjected to parasitological, histopathological,
      and enzyme assays, and immunological studies. The results showed that dietary
      zinc supplementation led to marked reduction in worm load, and egg deposition in
      the liver and intestine. Histopathological examination showed marked reduction in
      the number and diameter of hepatic granulomas in the treated groups. The activity
      of arylesterase and PON1 enzymes were partially restored in infected animals
      receiving zinc. IL-10 mRNA expression was higher in the treated groups than in
      the infection control group. In conclusion, zinc administration could be a
      promising adjuvant therapy for S. mansoni infection.

PMID- 19389400
TI  - Toxoplasma gondii: effects of Artemisia annua L. on susceptibility to infection
      in experimental models in vitro and in vivo.
AB  - Considering that the treatment for toxoplasmosis is based on drugs that show
      limited efficacy due to their substantial side effects, the purpose of the
      present study was to evaluate the effects of Artemisia annua on in vitro and in
      vivo Toxoplasma gondii infection. A. annua infusion was prepared from dried herb
      and tested in human foreskin fibroblasts (HFF) or mice that were infected with
      the parasite and compared with sulfadiazine treatment. For in vitro experiments,
      treatment was done on parasite before HFF infection or on cells previously
      infected with T. gondii and the inhibitory concentration (IC(50)) values for each
      treatment condition were determined. Viability of HFF cells in the presence of
      different concentrations of A. annua infusion and sulfadiazine was above 72%,
      even when the highest concentrations from both treatments were tested. Also, the
      treatment of T. gondii tachyzoites with A. annua infusion before infection in HFF
      cells showed a dose-response inhibitory curve that reached up to 75% of
      inhibition, similarly to the results observed when parasites were treated with
      sulfadiazine. In vivo experiments with a cystogenic T. gondii strain demonstrated
      an effective control of infection using A. annua infusion. In conclusion, our
      results indicate that A. annua infusion is useful to control T. gondii infection,
      due to its low toxicity and its inhibitory action directly against the parasite,
      resulting in a well tolerated therapeutic tool.

PMID- 19389401
TI  - Entamoeba histolytica: cysteine proteinase activity and virulence. Focus on
      cysteine proteinase 5 expression levels.
AB  - Cysteine proteinase (CP) activity and CP5 mRNA levels were analyzed in eleven
      samples of Entamoeba histolytica isolated from patients presenting different
      clinical profiles. The virulence degree of the isolates, determined in hamster
      liver, correlated well with the clinical form of the patient and culture
      conditions. CP5 mRNA levels were also determined in sample freshly picked up
      directly from liver amoebic abscess. Differences were not observed in the levels
      of CP5 mRNA and CP specific activity among the cultured samples. However,
      different levels of CP5 mRNA were observed in trophozoite freshly isolated from
      hepatic amoebic lesions. These results reinforce the importance of CP5 for the
      virulence of amoebae and the need for studies with the parasite present in
      lesions to validate mechanisms involved in pathogenesis of amoebiasis.

PMID- 19389402
TI  - Ovarian steroidogenesis inhibition by constant photothermal conditions is caused
      by a lack of gonadotropin stimulation in Eurasian perch.
AB  - In fish, the reasons for the inhibition of reproduction by constant photothermal
      conditions of rearing are far from clear. In an in vivo experiment, two groups of
      females reared under natural (4-28 degrees C) or constant photothermal conditions
      (20-22 degrees C, photoperiod 12/12) were investigated for gonad development, sex
      steroids (testosterone-T, 17-beta-estradiol-E2 and 11 Keto-Testosterone-11KT)
      dynamics and brain aromatase activity in January, February and March. Two days
      before each sampling date, a group of females reared under constant conditions
      was injected with HCG (Human Chorionic Gonadotropin: 100 UI/kg) and evaluated for
      the same parameters. In addition, in vitro ovarian steroidogenesis capacity for
      each female was determined with or without stimulation by HCG and/or IGF-1
      (Insulin-like Growth Factor-1). The results indicate that vitellogenesis stage is
      the limit ovarian stage never reached in females submitted to constant
      photothermal conditions. This was associated with gonadogenesis delay and low
      levels of circulating sex-steroids (T, E2 and 11KT). Nevertheless, HCG injections
      partly counteracted the plasma steroid deprivation, indicating that ovaries from
      fish reared under constant photothermal conditions suffer from a lack of
      gonadotropin stimulation, maybe caused by plasma LH suppression. Such finding was
      confirmed by the in vitro ovary incubation test. HCG and IGF-1 treatments induced
      broad testosterone and 17-beta-estradiol elevations and the exposure to constant
      photothermal conditions, in some cases, decreased that response to HCG. In
      conclusion, we show that the inhibition of reproductive cycle in Eurasian perch
      females by constant photothermal conditions of rearing may be related to lower
      sex-steroid levels and to an inhibition of ovarian regulation by gonadotropins
      (at least LH), probably stopping gonadogenesis before vitellogenesis stage.

PMID- 19389403
TI  - Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive
      cell therapy.
AB  - Adoptive cell therapy (ACT) for metastatic melanoma involves the ex vivo
      expansion and reinfusion of tumor infiltrating lymphocytes (TIL) obtained from
      resected specimens. With an overall objective response rate of 56%, this T-cell
      immunotherapy provides an appealing alternative to other therapies, including
      conventional therapies with lower response rates. However, there are significant
      regulatory and logistical concerns associated with the ex vivo activation and
      large-scale expansion of these cells. The best current practice uses a rapid
      expansion protocol (REP) consisting of an ex vivo process that occurs in tissue
      culture flasks (T-flasks) and gas-permeable bags, utilizes OKT3 (anti-CD3
      monoclonal antibody), recombinant human interleukin-2, and irradiated peripheral
      blood mononuclear cells to initiate rapid lymphocyte growth. A major limitation
      to the widespread delivery of therapy to large numbers of melanoma patients is
      the open system in which a REP is initiated. To address this problem, we have
      investigated the initiation, expansion and harvest at clinical scale of TIL in a
      closed-system continuous perfusion bioreactor. Each cell product met all safety
      criteria for patient treatment and by head-to-head comparison had a similar
      potency and phenotype as cells grown in control T-flasks and gas-permeable bags.
      However, the currently available bioreactor cassettes were limited in the total
      cell numbers that could be generated. This bioreactor may simplify the process of
      the rapid expansion of TIL under stringent regulatory conditions thereby enabling
      other institutions to pursue this form of ACT.

PMID- 19389404
TI  - Fine mapping of the sequence requirements for binding of beta-lactamase
      inhibitory protein (BLIP) to TEM-1 beta-lactamase using a genetic screen for BLIP
      function.
AB  - Beta-lactamase inhibitory protein (BLIP) binds and inhibits a diverse collection
      of class A beta-lactamases with a wide range of affinities. Alanine-scanning
      mutagenesis was previously performed to identify the amino acid sequence
      requirements of BLIP for binding the TEM-1, SME-1, SHV-1, and Bla1 beta
      lactamases. Twenty-three BLIP residues that contact TEM-1 beta-lactamase in the
      structure of the complex were mutated to alanine and assayed for inhibition
      (K(i)) of beta-lactamase to identify two hotspots of binding energy. These
      studies have been extended by the development of a genetic screen for BLIP
      function in Escherichia coli. The bla(TEM-1) gene encoding TEM-1 beta-lactamase
      was inserted into the E. coli pyrF chromosomal locus. Expression of wild-type
      BLIP from a plasmid in this strain resulted in a large decrease in ampicillin
      resistance, while introduction of the same plasmid lacking BLIP had no effect on
      ampicillin resistance. In addition, it was found that when the BLIP alanine
      scanning mutants were tested in the strain, the level of ampicillin resistance
      was proportional to the K(i) of the BLIP mutant. These results indicate that BLIP
      function can be monitored by the level of ampicillin resistance of the genetic
      test strain. Each of the 23 BLIP positions examined by alanine scanning was
      randomized to create libraries containing all possible substitutions at each
      position. The genetic screen for BLIP function was used to sort the libraries for
      active mutants, and DNA sequence analysis of functional BLIP mutants identified
      the sequences required for binding TEM-1 beta-lactamase. The results indicate the
      BLIP surface is tolerant of substitutions in that many contact positions can be
      substituted with other amino acid types and retain wild-type levels of function.

PMID- 19389405
TI  - Bacillus anthracis lethal toxin represses MMTV promoter activity through
      transcription factors.
AB  - We have recently shown that the anthrax lethal toxin (LeTx) selectively represses
      nuclear hormone receptors. In this study, we found that LeTx repressed the
      activation of the mouse mammary tumor virus promoter related to overexpression of
      the transcription factors hepatocyte nuclear factor 3, octamer-binding protein 1,
      and c-Jun. LeTx transcriptional repression was associated with a decrease in the
      protein levels of these transcription factors in a lethal factor protease
      activity-dependent manner. Early administration of LeTx antagonists partially or
      completely abolished the repressive effects of LeTx. In contrast to the rapid
      cleavage of mitogen-activated protein kinase kinases by LeTx, the degradation of
      these transcription factors occurred at a relatively late stage after LeTx
      treatment. In addition, LeTx repressed phorbol-12-myristate-13-acetate-induced
      mouse mammary tumor virus promoter activity and phorbol 12-myristate 13-acetate
      induction of endogenous c-Jun protein. Collectively, these findings suggest that
      transcription factors are intracellular targets of LeTx and expand our
      understanding of the molecular action of LeTx at a later stage of low-dose
      exposure.

PMID- 19389406
TI  - Polymerase-tailored variations in the water-mediated and substrate-assisted
      mechanism for nucleotidyl transfer: insights from a study of T7 DNA polymerase.
AB  - The nucleotidyl transfer reaction catalyzed by DNA polymerases is the critical
      step governing the accurate transfer of genetic information during DNA
      replication, and its malfunctioning can cause mutations leading to human
      diseases, including cancer. Here, utilizing ab initio quantum
      mechanical/molecular mechanical calculations with free-energy perturbation, we
      carried out an extensive investigation of the nucleotidyl transfer reaction
      mechanism in the well-characterized high-fidelity replicative DNA polymerase from
      phage T7. Our defined mechanism entails an initial concerted deprotonation of a
      conserved crystal water molecule with protonation of the gamma-phosphate of the
      deoxynucleotide triphosphate(dNTP) via a solvent water molecule, and then the
      proton on the primer 3'-terminus is transferred to the resulting hydroxide ion.
      Subsequently, the nucleophilic attack takes place, with the formation of a
      metastable pentacovalent phosphorane intermediate. Finally, the pyrophosphate
      leaves, facilitated by the relay of the proton on the gamma-phosphate to the
      alpha-beta bridging oxygen via solvent water. The computed activation free-energy
      barrier is consistent with kinetic data for the chemistry step with correct
      nucleotide incorporation in T7 DNA polymerase. This variant of the water-mediated
      and substrate-assisted mechanism has features tailored to the structure of the T7
      DNA polymerase. However, a unifying theme in the water-mediated and substrate
      assisted mechanism is the cycling through crystal and solvent water molecules of
      the proton originating from the primer 3'-terminus to the alpha-beta bridging
      oxygen of the deoxynucleotide triphosphate; this neutralizes the evolving
      negative charge as pyrophosphate leaves and restores the polymerase to its pre
      chemistry state. These unifying features are likely requisite elements for
      nucleotidyl transfer reactions.

PMID- 19389407
TI  - Ectopic recombination of a malaria var gene during mitosis associated with an
      altered var switch rate.
AB  - The Plasmodium falciparum var multigene family encodes P. falciparum erythrocyte
      membrane protein 1, which is responsible for the pathogenic traits of antigenic
      variation and adhesion of infected erythrocytes to host receptors during malaria
      infection. Clonal antigenic variation of P. falciparum erythrocyte membrane
      protein 1 is controlled by the switching between exclusively transcribed var
      genes. The tremendous diversity of the var gene repertoire both within and
      between parasite strains is critical for the parasite's strategy of immune
      evasion. We show that ectopic recombination between var genes occurs during
      mitosis, providing P. falciparum with opportunities to diversify its var
      repertoire, even during the course of a single infection. We show that the
      regulation of the recombined var gene has been disrupted, resulting in its
      persistent activation although the regulation of most other var genes is
      unaffected. The var promoter and intron of the recombined var gene are not
      responsible for its atypically persistent activity, and we conclude that altered
      subtelomeric cis sequence is the most likely cause of the persistent activity of
      the recombined var gene.

PMID- 19389408
TI  - An extended structure of the APOBEC3G catalytic domain suggests a unique
      holoenzyme model.
AB  - Human APOBEC3G (A3G) belongs to a family of polynucleotide cytidine deaminases.
      This family includes APOBEC1 and AID, which edit APOB mRNA and antibody gene DNA,
      respectively. A3G deaminates cytidines to uridines in single-strand DNA and
      inhibits the replication of human immunodeficiency virus-1, other retroviruses,
      and retrotransposons. Although the mechanism of A3G-catalyzed DNA deamination has
      been investigated genetically and biochemically, atomic details are just starting
      to emerge. Here, we compare the DNA cytidine deaminase activities and NMR
      structures of two A3G catalytic domain constructs. The longer A3G191-384 protein
      is considerably more active than the shorter A3G198-384 variant. The longer
      structure has an alpha1-helix (residues 201-206) that was not apparent in the
      shorter protein, and it contributes to catalytic activity through interactions
      with hydrophobic core structures (beta1, beta3, alpha5, and alpha6). Both A3G
      catalytic domain solution structures have a discontinuous beta2 region that is
      clearly different from the continuous beta2 strand of another family member,
      APOBEC2. In addition, the longer A3G191-384 structure revealed part of the N
      terminal pseudo-catalytic domain, including the interdomain linker and some of
      the last alpha-helix. These structured residues (residues 191-196) enabled a
      novel full-length A3G model by providing physical overlap between the N-terminal
      pseudo-catalytic domain and the new C-terminal catalytic domain structure.
      Contrary to predictions, this structurally constrained model suggested that the
      two domains are tethered by structured residues and that the N- and C-terminal
      beta2 regions are too distant from each other to participate in this interaction.

PMID- 19389409
TI  - Mathematical modeling of viral kinetics under immune control during primary HIV-1
      infection.
AB  - Primary human immunodeficiency virus (HIV) infection is characterized by an
      initial exponential increase of viral load in peripheral blood reaching a peak,
      followed by a rapid decline to the viral setpoint. Although the target-cell
      limited model can account for part of the viral kinetics observed early in
      infection [Phillips, 1996. Reduction of HIV concentration during acute infection:
      independence from a specific immune response. Science 271 (5248), 497-499], it
      frequently predicts highly oscillatory kinetics after peak viremia, which is not
      typically observed in clinical data. Furthermore, the target-cell-limited model
      is unable to predict long-term viral kinetics, unless a delayed immune effect is
      assumed [Stafford et al., 2000. Modeling plasma virus concentration during
      primary HIV infection. J. Theor. Biol. 203 (3), 285-301]. We show here that
      extending the target-cell-limited model, by implementing a saturation term for
      HIV-infected cell loss dependent upon infected cell levels, is able to reproduce
      the diverse observed viral kinetic patterns without the assumption of a delayed
      immune response. Our results suggest that the immune response may have
      significant effect on the control of the virus during primary infection and may
      support experimental observations that an anti-HIV immune response is already
      functional during peak viremia.

PMID- 19389410
TI  - A possible mechanism for the dynamics of transition between polymerase and
      exonuclease sites in a high-fidelity DNA polymerase.
AB  - The fidelity of DNA synthesis by DNA polymerase is significantly increased by a
      mechanism of proofreading that is performed at the exonuclease active site
      separate from the polymerase active site. Thus, the transition of DNA between the
      two active sites is an important activity of DNA polymerase. Here, based on our
      proposed model, the rates of DNA transition between the two active sites are
      theoretically studied. With the relevant parameters, which are determined from
      the available crystal structure and other experimental data, the calculated
      transfer rate of correctly base-paired DNA from the polymerase to exonuclease
      sites and the transfer rate after incorporation of a mismatched base are in good
      agreement with the available experimental data. The transfer rates in the
      presence of two and three mismatched bases are also consistent with the previous
      experimental data. In addition, the calculated transfer rate from the exonuclease
      to polymerase sites has a large value even with the high binding affinity of 3'
      5' ssDNA for the exonuclease site, which is also consistent with the available
      experimental value. Moreover, we also give some predictive results for the
      transfer rate of DNA containing only A:T base pairs and that of DNA containing
      only G:C base pairs.

PMID- 19389411
TI  - Effects of chemical species of selenium on maternal transfer during pregnancy and
      lactation.
AB  - AIMS: This study compares the transfer from mother to fetuses and pups of
      selenium (Se) in the form of selenite, selenate, and selenomethionine (SeMet)
      labeled with different homo-elemental isotopes. MAIN METHODS: To completely
      substitute endogenous Se with natural abundance with Se enriched with a single
      stable isotope (82Se), female Wistar rats delivered by mother fed 82Se-selenite
      were fed Se-deficient diet and drinking water containing 82Se-selenite
      immediately after weaning, and then mated with male Wistar rat at the age of 15
      17 weeks. The pregnant rats were divided into two groups. One group was fed Se
      deficient diet and drinking water containing 76Se-selenite, 78Se-selenate, and
      77Se-SeMet from gestation days 11 to 20. The other group was fed the same diet
      and drinking water containing the three Se species after delivery for 10 days of
      lactation. Non-pregnant rats were also fed Se mixture and Se-deficient diet for
      10 days. KEY FINDING: Tissue and plasma Se concentrations showed significant
      changes among non-pregnant, pregnant, and lactating rats. The peak corresponding
      to selenoprotein P (Sel P) in serum of pregnant rats was reduced. The
      concentration of 77Se originating from SeMet was higher than those of 76Se from
      selenite and 78Se from selenate in the stomach content of pups. SIGNIFICANCE:
      Inorganic Se species are more preferably transformed into Sel P than SeMet, and
      Sel P is effectively incorporated into placenta during pregnancy. On the other
      hand, SeMet is a more efficient Se source than inorganic Se species during
      lactation.

PMID- 19389412
TI  - Methylamine dichloramine may play a role in the process of colorectal disease
      through architectural and oxidative changes in crypts in mice.
AB  - AIMS: Methylamine dichloramine (CH(3)NCl(2)) produced by neutrophils may promote
      colon tumors and colitis via architectural and oxidative changes in crypts, which
      are secretory granulae composed of goblet cells located in the colorectal mucosal
      layer. We investigated whether CH(3)NCl(2), in comparison with the other reactive
      oxygen species (ROS) such as H(2)O(2) and HOCl, derived from primed neutrophils
      in inflammatory sites in the large intestine, is a biogenic factor for the
      induction of colorectal disease in mice. MAIN METHODS: Male ICR-strain mice were
      administered each oxidant (0.5-0.7 micromol/mouse) by enema under anesthesia. The
      colorectal tissues were evaluated by histopathological and immunohistochemical
      analyses. Hemolysis and hemoglobin oxidation by the methylamine chloramines and
      HOCl were examined by adding them (50-400 microM) to a sheep erythrocyte
      suspension (1x10(8) cells/ml) and its lysate at pH 7 and 37 degrees C. KEY
      FINDINGS: CH(3)NCl(2) oxidized erythrocyte hemoglobin more effectively than HOCl,
      indicating it has high cell permeability and selective oxidation ability.
      CH(3)NCl(2) mainly induced atrophy of crypts at 6 h after administration, while
      the other ROS tested did not. Furthermore, 4-hydroxy-2-nonenal (4-HNE) showed
      positive immunostains throughout the mucosal layer, including around the basal
      regions of atrophied crypts, only with CH(3)NCl(2), while positive immunostains
      were observed for 3-nitrotyrosine (3-NT) in the atrophied crypts and their
      surrounding lamina propria in the mucosal layer. SIGNIFICANCE: The results
      suggest that CH(3)NCl(2)derived from primed neutrophils may play the most
      important role in promoting the development of colon tumor formation and colitis
      by oxidative stress through its high degree of cell permeability.

PMID- 19389413
TI  - Heparin-binding EGF-like growth factor is a potent dilator of terminal mesenteric
      arterioles.
AB  - OBJECTIVE: We have previously shown that heparin-binding EGF-like growth factor
      (HB-EGF) protects the intestines from multiple forms of injury via direct
      cytoprotective effects on the intestinal mucosa. In this study, we examined the
      effects of HB-EGF on the hemodynamics of intestinal arterioles, the major
      resistance vessels that regulate blood flow to the intestines, as an additional
      mechanism of HB-EGF-mediated intestinal protection. METHODS: The hemodynamic
      effects of HB-EGF in rodent terminal mesenteric arterioles and human submucosal
      arterioles were examined ex vivo using a video dimension analyzer. Cultured human
      intestinal microvascular endothelial cells (HIMEC) were used to elucidate the
      mechanisms of HB-EGF-induced vasodilation. RESULTS: HB-EGF significantly
      increased vessel diameter under conditions of increasing intraluminal pressure
      and increased flow rate. These HB-EGF-mediated vasodilatory effects were observed
      in terminal mesenteric arterioles from adult rats and 3 day old rat pups. These
      effects were confirmed in submucosal arterioles from human intestine.
      Furthermore, HB-EGF significantly reduced endothelin-1-induced mesenteric
      arteriolar vasoconstriction. The vasodilatory effects of HB-EGF were blocked by
      ET(B) receptor antagonism in adult rat arterioles, and also by nitric oxide
      synthase inhibition in rat pup and human infant arterioles. In HIMEC, HB-EGF
      significantly increased endothelin B (ET(B)) receptor protein expression and
      provoked intracellular calcium mobilization. CONCLUSIONS: HB-EGF is a potent
      vasodilator of the intestinal microvasculature, further supporting its use in
      diseases manifested by decreased intestinal blood flow, including necrotizing
      enterocolitis.

PMID- 19389415
TI  - Bioaccumulation potential of air contaminants: combining biological allometry,
      chemical equilibrium and mass-balances to predict accumulation of air pollutants
      in various mammals.
AB  - In the present study we develop and test a uniform model intended for single
      compartment analysis in the context of human and environmental risk assessment of
      airborne contaminants. The new aspects of the model are the integration of
      biological allometry with fugacity-based mass-balance theory to describe exchange
      of contaminants with air. The developed model is applicable to various mammalian
      species and a range of chemicals, while requiring few and typically well-known
      input parameters, such as the adult mass and composition of the species, and the
      octanol-water and air-water partition coefficient of the chemical. Accumulation
      of organic chemicals is typically considered to be a function of the chemical
      affinity for lipid components in tissues. Here, we use a generic description of
      chemical affinity for neutral and polar lipids and proteins to estimate blood-air
      partition coefficients (K(ba)) and tissue-air partition coefficients (K(ta)) for
      various mammals. This provides a more accurate prediction of blood-air partition
      coefficients, as proteins make up a large fraction of total blood components. The
      results show that 68% of the modeled inhalation and exhalation rate constants are
      within a factor of 2.1 from independent empirical values for humans, rats and
      mice, and 87% of the predicted blood-air partition coefficients are within a
      factor of 5 from empirical data. At steady-state, the bioaccumulation potential
      of air pollutants is shown to be mainly a function of the tissue-air partition
      coefficient and the biotransformation capacity of the species and depends weakly
      on the ventilation rate and the cardiac output of mammals.

PMID- 19389414
TI  - Sleep-dependent gene expression in the hippocampus and prefrontal cortex
      following long-term potentiation.
AB  - The activity-dependent transcription factor zif268 is re-activated in sleep
      following hippocampal long-term potentiation (LTP). However, the activation of
      secondary genes, possibly involved in modifying local synaptic strengths and
      ultimately stabilizing memory traces during sleep, has not yet been studied.
      Here, we investigated changes in hippocampal and cortical gene expression at a
      time point subsequent to the previously reported initial zif268 re-activation
      during sleep. Rats underwent unilateral hippocampal LTP and were assigned to
      SLEEP or AWAKE groups. Eighty minutes after a long rapid-eye-movement sleep
      (REMS) episode (or an equivalent amount of time for awake group) animals had
      their hippocampi dissected and processed for gene microarray hybridization.
      Prefrontal and parietal cortices were also collected for qRT-PCR analysis. The
      microarray analysis identified 28 up-regulated genes in the hippocampus: 11 genes
      were enhanced in the LTPed hemisphere of sleep animals; 13 genes were enhanced
      after sleep, regardless of hemisphere; and 4 genes were enhanced in LTPed
      hemisphere, regardless of behavioral state. qRT-PCR analysis confirmed the up
      regulation of aif-1 and sc-65 during sleep. Moreover, we observed a down
      regulation of the purinergic receptor, P2Y4R in the LTP hemisphere of awake
      animals and a trend for the protein kinase, CaMKI to be up-regulated in the LTP
      hemisphere of sleep animals. In the prefrontal cortex, we showed a significant
      LTP-dependent down-regulation of gluR1 and spinophilin specifically during sleep.
      Zif268 was down-regulated in sleep regardless of the hemisphere. No changes in
      gene expression were observed in the parietal cortex. Our findings indicate that
      a set of synaptic plasticity-related genes have their expression modulated during
      sleep following LTP, which can reflect biochemical events associated with
      reshaping of synaptic connections in sleep following learning.

PMID- 19389416
TI  - Suppression wave dynamics: visual field anisotropies and inducer strength.
AB  - We used binocular rivalry and generalized flash suppression to identify several
      new shared properties of traveling suppression waves. A strong relationship was
      found between suppression wave speed and induction pulse strength: increasing the
      contrast or dot density of the induction pulse led to an increase in wave speed.
      Evidence of visual field anisotropies in wave propagation speeds were also seen,
      with suppression waves decelerating as they travel towards the fovea. This
      deceleration could not be accounted for by cortical magnification in lower level
      brain areas, suggesting an important role for other, yet to be identified,
      factors.

PMID- 19389417
TI  - The influence of vergence adaptation on open-loop vergence dynamics.
AB  - The objectives of this experiment were to measure the effect of sustained
      convergence on the open-loop vergence peak velocity and open-loop vergence
      amplitude, and to assess the correlation between changes in the phoria and
      changes in open-loop vergence peak velocity induced by sustained convergence.
      Subjects sustained convergence on a target that required 12 degrees of
      convergence for 5 minutes. Convergence and divergence movements of 4 degrees from
      the 12 degrees convergent position were measured before and after sustained
      convergence. Following sustained convergence, the open-loop vergence peak
      velocity and vergence amplitude both increased for convergence (regression
      slope=3.68, r=0.47). Vergence velocity and vergence amplitude both decreased for
      divergence (regression slope=1.76, r=0.36). After sustained convergence, a
      convergent shift in the phoria was noted in most cases. This shift correlated
      with changes in open-loop peak vergence velocity more for convergence (regression
      slope=1.1, r=0.33) than for divergence (regression slope=0.71, r=0.22). The
      results might be due to shifts in disparity detection brought about by the period
      of sustained convergence.

PMID- 19389418
TI  - Limitations of the ocular wavefront correction with contact lenses.
AB  - We analyze theoretically, by means of both computer simulations and laboratory
      experiments, the limitations of correcting aberrations with ideal customized
      contact lenses. Four experiments are presented: In the first one, we have
      analyzed the limitations of a static correction on the dynamic wavefront. In the
      second one, we studied the rotations of a contact lens on the eye using an
      optical method. The third one researched the limitations of the wavefront
      correction, focusing on a group of normal and highly aberrated eyes, when the
      correction suffers from a permanent rotation or translation. The fourth one
      estimates, under a simple approximation, the error made when applying on the
      corneal plane the correction corresponding to the wavefront measured at the
      entrance-pupil plane. Results show that a static correction of the wavefront
      leaves a residual aberration of 0.15-0.25 microm for a 5 mm pupil. Rotation of
      the contact lens (up to +/-4 degrees) diminishes the effectiveness of the
      correction. Horizontal or vertical translations of 0.5mm could generate a high
      order-aberration RMS that is higher than the remaining one after a standard low
      order correction. In particular, the group of eyes having normal values of high
      order aberrations are more sensitive to translations than the one having higher
      values. Most of the results could be applied to other methods of aberration
      correction, such as refractive surgery or correction by means of intraocular
      lenses.

PMID- 19389420
TI  - Delivering prevention for alcohol and cannabis using the Internet: a cluster
      randomised controlled trial.
AB  - OBJECTIVE: To establish the efficacy of an internet based prevention program to
      reduce alcohol and cannabis use in adolescents. METHOD: A cluster randomised
      controlled trial was conducted with 764 13-year olds from ten Australian
      secondary schools in 2007-2008. Half the schools were randomly allocated to the
      computerised prevention program (n=397), and half to their usual health classes
      (n=367). The Climate Schools: Alcohol and Cannabis prevention course is
      facilitated by the internet and consists of novel, evidence-based, curriculum
      consistent lessons aimed at reducing alcohol and cannabis use. Participants were
      assessed at baseline, immediately post, and at six months following the
      intervention. RESULTS: Compared to the control group, students in the
      intervention group showed significant improvements in alcohol and cannabis
      knowledge at the end of the course and the six month follow-up. In addition, the
      intervention group showed a reduction in average weekly alcohol consumption and
      frequency of cannabis use at the six month follow-up. No differences between
      groups were found on alcohol expectancies, cannabis attitudes, or alcohol and
      cannabis related harms. CONCLUSIONS: The course is acceptable, scalable and
      fidelity is assured. It increased knowledge regarding alcohol and cannabis, and
      decreased use of these drugs.

PMID- 19389421
TI  - Promoting healthy lifestyles among adolescent boys: the Fitness Improvement and
      Lifestyle Awareness Program RCT.
AB  - OBJECTIVE: To assess the feasibility, acceptability, and potential efficacy of a
      school-based obesity prevention program among adolescent boys with sub-optimal
      cardiorespiratory fitness. METHODS: In 2007, a 6-month, 2-arm parallel group,
      randomized controlled pilot trial was conducted in a single school setting
      (Sydney, Australia). Thirty-three 7th Grade boys (mean age=12.5+/-0.4 years) were
      randomly assigned to intervention (n=16) or active comparison group (n=17). The
      intervention consisted of one 60-minute curriculum session and two 20-minute
      lunchtime physical activity sessions per week. The active comparison group
      continued with their usual physical activity curriculum sessions (Friday
      afternoons 2-3 pm). The pilot trial's curriculum sessions were additional to
      Physical Education (PE) lessons. The primary outcome was BMI, and secondary
      outcomes included waist circumference, percentage body fat, cardiorespiratory
      fitness, objectively measured physical activity and small screen recreation time.
      RESULTS: Screening, recruitment and retention goals were exceeded. The majority
      of data were collected as planned. Implementation and attendance rates were
      acceptable. At follow-up, compared with boys in the active comparison group, boys
      in the intervention group displayed a smaller increase in BMI (adjust diff.=-0.2,
      95% confidence interval [CI] -0.78, 0.39; Cohen's d=0.05); greater reductions in
      waist circumference (-1.65 cm [-4.67, 1.36]; d=0.15); percentage body fat (-1.69%
      [-4.98, 1.60]; d=0.22) and time spent in small screen recreation on weekends (
      1.13 h [-5.06, 2.80]; d=0.19); and a greater increase in cardiorespiratory
      fitness (2.13 laps [6.22, 10.48]; d=0.16); and participation in total weekday
      physical activity (140.74 counts/min [-159.44, 440.92]; d=0.36). CONCLUSIONS:
      This study verified the feasibility, acceptability and potential efficacy of a
      multifaceted school-based intervention to prevent unhealthy weight gain among
      adolescent boys.

PMID- 19389422
TI  - Echinacea for prevention of the common cold: an illustrative overview of how
      information from different systematic reviews is summarised on the internet.
AB  - OBJECTIVES: Three systematic reviews of echinacea for the prevention of colds
      have somewhat different conclusions. Our study objectives were to illustrate how
      selection criteria for trials in each of the reviews could lead to different
      conclusions, and to classify the ways in which webpage authors use the reviews to
      construct advice about echinacea. METHODS: A funnel plot was constructed of all
      treatment comparisons in the primary trials included in the reviews. A World Wide
      Web search was undertaken using five major search engines in order to locate
      webpages that referred to the efficacy of echinacea in cold prevention and also
      referred to each of the reviews. RESULTS: Twelve webpages were located. Three
      webpages presented findings from all three reviews; five presented findings from
      one or two; four used all three reviews as general supporting references. Views
      about efficacy differed. There were few comments about the sources of
      heterogeneity between reviews. CONCLUSIONS: Given the residual uncertainty and
      the gaps between the evidence and the ways that this is summarised on webpages,
      it may prove difficult for consumers to assimilate the evidence. As well as
      undertaking high-quality trials in complementary medicine, we also need to ensure
      precision in the reporting of uncertainty.

PMID- 19389423
TI  - Clustering of health-compromising behavior and delinquency in adolescents and
      adults in the Dutch population.
AB  - OBJECTIVE: This study investigates the clustering of a broad range of health
      compromising and delinquent behaviors. We examine whether these behaviors belong
      to a single but broad cluster, 'risk-taking behavior', and whether the nature and
      degree of clustering in adolescents differs from that in adults. METHOD: A
      representative sample (N=4395) of the Dutch population aged 12 to 40 (overall
      response rate 67%), was asked about various health-compromising behaviors, such
      as alcohol consumption, smoking, illegal drug use, unsafe sexual behavior,
      physical inactivity, poor nutrition (such as skipping breakfast and not eating
      fruit and vegetables), poor sleep behavior, unlawful traffic behavior, and
      delinquent and aggressive behavior. Data were collected from fall 2005 to spring
      2006 using internet questionnaires and face-to-face computer-assisted interviews.
      RESULTS: No single broad cluster was found. Instead, there were several separate
      but interrelated clusters. The contents of these clusters differed between age
      groups. For young adolescents (12-15) two clusters were identified: Alcohol and
      Delinquency. For older adolescents (16-18) and adults (19-40) three clusters were
      identified: Alcohol, Delinquency and Health. CONCLUSION: The findings of this
      study support a more integrated approach to promoting healthier lifestyles, and
      suggest that the behavior targets of integrated prevention programs should be
      different for adolescents and adults.

PMID- 19389424
TI  - Molecular cloning, expression in Escherichia coli and production of bioactive
      homogeneous recombinant human granulocyte and macrophage colony stimulating
      factor.
AB  - Human granulocyte and macrophage colony stimulating factor (hGM-CSF) is a
      glycoprotein that activates and enhances the differentiation and survival of
      neutrophils, eosinophils and macrophages, which play a key role in the innate
      immune response. Here we describe the construction of the hGM-CSF encoding gene,
      cloning, expression in Escherichia coli, purification of recombinant hGM-CSF, N
      terminal amino acid sequencing, and biological activity assay using TF-1 cells.
      The results presented show that the combination of experimental strategies
      employed to obtain recombinant hGM-CSF can yield biologically active protein, and
      may be useful to scaling-up production of biosimilar protein.

PMID- 19389426
TI  - B-1 cells modulate oral tolerance in mice.
AB  - Although the origin and functions of B-1 cells are controversial, they are
      considered as a cellular element of innate immunity due to their ability to
      produce natural autoantibodies of the IgM type. These antibodies are encoded by a
      relatively limited repertoire of V genes, and their resulting diversity is
      smaller than that produced by conventional B cells. B-1 cells constitute the
      larger fraction of B cells in the peritoneal cavity and migrate to non-specific
      inflammation sites. In addition, they contribute to the production of IgA
      antibodies in the intestinal lamina propria. It has been demonstrated that they
      participate in the induction and maintenance of peripheral tolerance. Herein, the
      participation of B-1 cells in inducing oral tolerance is evaluated. Unexpectedly,
      BALB/Xid mice, the animals deficient in B-1 cells, are not tolerized to OVA but
      instead are responsive to oral immunization. Conversely, BALB/c mice respond to
      oral tolerance to this antigen. We used these biological characteristics of these
      animals to investigate whether B-1 cells are involved in the induction of oral
      tolerance to OVA. Results show that B-1 cells from BALB/c mice, treated orally
      with OVA and adoptively transferred to BALB/Xid mice were able to suppress local
      hypersensitivity reaction and lymphoproliferative cellular response observed in
      BALB/Xid mice. These data demonstrate that B-1 cells have regulatory properties
      and are involved in the induction of oral tolerance.

PMID- 19389425
TI  - A novel short hairpin RNA (shRNA) expression system promotes Sox9-dependent gene
      silencing.
AB  - Cartilage development and function are dependent on a temporally integrated
      program of gene expression. With the advent of RNA interference (RNAi),
      artificial control of these complex programs becomes a possibility, limited only
      by the ability to regulate and express the RNAi. Using existing methods for
      production of RNAi's, we have constructed a plasmid-based short hairpin RNA
      (shRNA) expression system under control of the human pol III H1 promoter and
      supplemented this promoter with DNA binding sites for the cartilage-specific
      transcription factor Sox9. The resulting shRNA expression system displays robust,
      Sox9-dependent gene silencing. Dependence on Sox9 expression was confirmed by
      electrophoretic mobility shift assays. The ability of the system to regulate
      heterologously expressed Sox9 was demonstrated by Western blot, as a function of
      both Sox9 to shRNA ratio, as well as time from transfection. This novel
      expression system supports auto-regulatory gene silencing, providing a tissue
      specific feedback mechanism for temporal control of gene expression. Its
      applications for both basic mechanistic studies and therapeutic purposes should
      facilitate the design and implementation of innovative tissue engineering
      strategies.

PMID- 19389427
TI  - Effects of postnatal malnutrition and senescence on learning, long-term memory,
      and extinction in the rat.
AB  - There is a wealth of information indicating that the hippocampal formation is
      important for learning and memory consolidation. The hippocampus is very
      sensitive to ageing and developmentally stressful factors such as prenatal
      malnutrition, which produces anatomical alterations of hippocampal pyramidal
      cells as well as impaired spatial learning. On the other hand, there are no
      reports about differential effects of postnatal malnutrition, installed at birth
      and maintained all through life in young and aged rats, on learning and memory of
      active avoidance, a task with an important procedural component. We now report
      that learning and long-term retention of this task were impaired in young
      malnourished animals, but not in young control, senile control, and senile
      malnourished Sprague-Dawley rats; young and senile rats were 90 and 660 days of
      age, respectively. Extinction tests showed, however, that long-term memory of the
      malnourished groups and senile control animals is impaired as compared with the
      young control animals. These data strongly suggest that the learning and long
      term retention impairments seen in the young animals were due to postnatal
      malnutrition; in the senile groups, this cognitive alteration did not occur,
      probably because ageing itself is an important factor that enables the brain to
      engage in compensatory mechanisms that reduce the effects of malnutrition.
      Nonetheless, ageing and malnutrition, conditions known to produce anatomic and
      functional hippocampal alterations, impede the maintenance of long-term memory,
      as seen during the extinction test.

PMID- 19389428
TI  - Habituation-induced neural plasticity in the hippocampus and prefrontal cortex
      mediated by MMP-3.
AB  - Head-shake response (HSR) habituation was presently used to investigate the
      phenomena of spontaneous recovery and neural plasticity. Independent groups of
      rats were presented with five consecutive habituation sessions separated by inter
      session intervals (ISIs) of 2, 24 or 72 h. At the conclusion of testing
      hippocampus and prefrontal cortex tissue samples were collected for determination
      of matrix metalloproteinase-3 (MMP-3:stromelysin-1) expression as a marker of
      neural plasticity. The results indicated that by the fifth session the 2 h ISI
      group showed no spontaneous recovery, the 72 h ISI group revealed nearly complete
      spontaneous recovery; while the 24 h ISI group showed intermediate recovery. MMP
      3 expression in the hippocampus and prefrontal cortex was elevated in the 2 and
      72 h ISI groups, but not in the 24 h group. A second experiment utilized 7-day
      osmotic pumps to intracerebroventricularly infuse an MMP-3 inhibitor for 6 days.
      The animals were then tested on the seventh day using the 2 h ISI protocol.
      Delivery of the MMP-3 inhibitor facilitated spontaneous recovery, thus
      compromising the animal's ability to appropriately habituate. This effect was
      accompanied by a significant inhibition of hippocampus and prefrontal cortex MMP
      3 expression. These results suggest that elevations in hippocampus and prefrontal
      cortex MMP-3 expression contribute to this simplest form of learning and may be a
      mechanism underlying spontaneous recovery.

PMID- 19389429
TI  - Variations in illumination, closed wall transparency and/or extramaze space
      influence both baseline anxiety and response to diazepam in the rat elevated plus
      maze.
AB  - Numerous methodological-related variables have been demonstrated to influence the
      baseline anxiety level of rodents exposed to the elevated plus-maze (EPM),
      raising questions about the sensitivity of this test for the detection of the
      effects of anxiolytic drugs. Thus, the present study was designed (1) to assess
      the combined effects of illumination (40-lx red or white light), closed wall type
      (walls made of translucent or opaque material) and extramaze space size (small or
      spacious experimental room) on rat behaviour, and (2) to investigate the effects
      of such parameters on the relevance of the maze for detecting the effects of
      diazepam orally administrated at the anxiolytic dose of 3 mg/kg. Results indicate
      that illumination and closed wall type are two main independent parameters that
      are able to modify the open arm avoidance. Moreover, the closed wall type
      interacts with the extramaze space size since the reduction of the open arm
      exploration induced by opaque closed walls is two-fold stronger in the spacious
      experimental room than in the small one. Finally, the diazepam anxiolytic
      activity is significantly detected in our laboratory in specific EPM conditions
      (maze with opaque walls, use of a red light, maze located in a spacious
      experimental room). In conclusion, the present study demonstrates that an
      inappropriate baseline anxiety level due to the methodological use of the EPM can
      dramatically reduce the sensitivity of the maze for the detection of
      benzodiazepine-related compounds. This study also provides new insights into the
      perception of the EPM open space in rats.

PMID- 19389430
TI  - Screening for peptides binding on Phytophthora capsici extracts by phage display.
AB  - Phytophthora blight of pepper is a completely destructive plant disease caused by
      the oomycete pathogen Phytophthora capsici Leonian. Phytophthora disease is
      responsible for major losses in pepper production and the pathogen can survive in
      soil in the absence of the host plant for many years. Currently, there are no
      early diagnostic reagents available that specifically target P. capsici.
      Therefore, diagnostic tools that can detect Phytophthora are required. In the
      present study, we screened for P. capsici-binding peptides using M13 phage
      display. After five rounds of biopanning, we identified P. capsici-binding
      peptides from a random peptide library that showed high binding affinity and
      specificity toward P. capsici in the picomolar range. These peptides can be used
      to develop novel diagnostic probes or potent inhibitors with diverse
      polyvalencies.

PMID- 19389431
TI  - Optimization of three FISH procedures for in situ detection of anaerobic ammonium
      oxidizing bacteria in biological wastewater treatment.
AB  - Fluorescence in situ hybridization (FISH) using fluorochrome-labeled DNA
      oligonucleotide probes has been successfully applied for in situ detection of
      anaerobic ammonium oxidizing (anammox) bacteria. However, application of the
      standard FISH protocols to visualize anammox bacteria in biofilms from a
      laboratory-scale wastewater reactor produced only weak signals. Increased signal
      intensity was achieved either by modifying the standard FISH protocol, using
      peptide nucleic acid probes (PNA FISH), or applying horse radish peroxidase- (HRP
      ) labeled probes and subsequent catalyzed reporter deposition (CARD-FISH). A
      comparative analysis using anammox biofilm samples and suspended anammox biomass
      from different laboratory wastewater bioreactors revealed that the modified
      standard FISH protocol and the PNA FISH probes produced equally strong
      fluorescence signals on suspended biomass, but only weak signals were obtained
      with the biofilm samples. The probe signal intensities in the biofilm samples
      could be enhanced by enzymatic pre-treatment of fixed cells, and by increasing
      the hybridization time of the PNA FISH protocol. CARD-FISH always produced up to
      four-fold stronger fluorescent signals but unspecific fluorescence signals,
      likely caused by endogenous peroxidases as reported in several previous studies,
      compromised the results. Interference of the development of fluorescence
      intensity with endogenous peroxidases was also observed in cells of aerobic
      ammonium oxidizers like Nitrosomonas europea, and sulfate-reducers like
      Desulfobacter postgatei. Interestingly, no interference was observed with other
      peroxidase-positive microorganisms, suggesting that CARD-FISH is not only
      compromised by the mere presence of peroxidases. Pre-treatment of cells to
      inactivate peroxidase with HCl or autoclavation/pasteurization failed to inactive
      peroxidases, but H(2)O(2) significantly reduced endogenous peroxidase activity.
      However, for optimal inactivation, different H(2)O(2) concentrations and
      incubation time may be needed, depending on nature of sample and should therefore
      always be individually determined for each study.

PMID- 19389432
TI  - Degradation kinetics of stabilized Pluronic micelles under the action of
      ultrasound.
AB  - The majority of research in the area of acoustically-activated drug delivery from
      stabilized micelles has been focused on the rapid release of chemotherapy drugs
      from the core of such nano-carriers. Previous publications have shown that low
      frequency ultrasound is able to release approximately 2% of Doxorubicin (Dox)
      from the core of Pluronic P105 micelles stabilized using a cross-linked network
      of N,N-diethylacrylamide (NanoDeliv) within 2 s of applying 70-kHz ultrasound.
      Here we use a custom-made ultrasound exposure chamber with fluorescence detection
      to measure the long-term fluorescence emissions of Dox from the NanoDeliv after 2
      h of exposure to two ultrasound frequencies, 70 and 476 kHz, at a mechanical
      index of 0.9. Fluorescence measurements are then used to deduce the degradation
      kinetics of stabilized Pluronic micelles during 24 h following exposure to
      ultrasound. Results show that ultrasound does disrupt the covalent network of the
      stabilized micelles, but the time constant of network degradation is very long
      compared to the time constant pertaining to drug release from micelles.
      Experiments also show no significant difference in degradation rates when
      employing the two frequencies in question at the same mechanical index.

PMID- 19389433
TI  - Zebrafish as a correlative and predictive model for assessing biomaterial
      nanotoxicity.
AB  - The lack of correlative and predictive models to assess acute and chronic
      toxicities limits the rapid pre-clinical development of new therapeutics. This
      barrier is due in part to the exponential growth of nanotechnology and
      nanotherapeutics, coupled with the lack of rigorous and robust screening assays
      and putative standards. It is a fairly simple and cost-effective process to
      initially screen the toxicity of a nanomaterial by using invitro cell cultures;
      unfortunately it is nearly impossible to imitate a complimentary invivo system.
      Small mammalian models are the most common method used to assess possible
      toxicities and biodistribution of nanomaterials in humans. Alternatively,
      Daniorerio, commonly known as zebrafish, are proving to be a quick, cheap, and
      facile model to conservatively assess toxicity of nanomaterials.

PMID- 19389435
TI  - Towards therapeutic application of RNA-mediated gene regulation. Preface.

PMID- 19389436
TI  - siRNA vs. shRNA: similarities and differences.
AB  - RNA interference (RNAi) is a natural process through which expression of a
      targeted gene can be knocked down with high specificity and selectivity. Using
      available technology and bioinformatics investigators will soon be able to
      identify relevant bio molecular tumor network hubs as potential key targets for
      knockdown approaches. Methods of mediating the RNAi effect involve small
      interfering RNA (siRNA), short hairpin RNA (shRNA) and bi-functional shRNA. The
      simplicity of siRNA manufacturing and transient nature of the effect per dose are
      optimally suited for certain medical disorders (i.e. viral injections). However,
      using the endogenous processing machinery, optimized shRNA constructs allow for
      high potency and sustainable effects using low copy numbers resulting in less off
      target effects, particularly if embedded in a miRNA scaffold. Bi-functional
      design may further enhance potency and safety of RNAi-based therapeutics.
      Remaining challenges include tumor selective delivery vehicles and more complete
      evaluation of the scope and scale of off-target effects. This review will compare
      siRNA, shRNA and bi-functional shRNA.

PMID- 19389434
TI  - Magnetic nanoparticles for theragnostics.
AB  - Engineered magnetic nanoparticles (MNPs) represent a cutting-edge tool in
      medicine because they can be simultaneously functionalized and guided by a
      magnetic field. Use of MNPs has advanced magnetic resonance imaging (MRI), guided
      drug and gene delivery, magnetic hyperthermia cancer therapy, tissue engineering,
      cell tracking and bioseparation. Integrative therapeutic and diagnostic (i.e.,
      theragnostic) applications have emerged with MNP use, such as MRI-guided cell
      replacement therapy or MRI-based imaging of cancer-specific gene delivery.
      However, mounting evidence suggests that certain properties of nanoparticles
      (e.g., enhanced reactive area, ability to cross cell and tissue barriers,
      resistance to biodegradation) amplify their cytotoxic potential relative to
      molecular or bulk counterparts. Oxidative stress, a 3-tier paradigm of
      nanotoxicity, manifests in activation of reactive oxygen species (ROS) (tier I),
      followed by a proinflammatory response (tier II) and DNA damage leading to
      cellular apoptosis and mutagenesis (tier III). Invivo administered MNPs are
      quickly challenged by macrophages of the reticuloendothelial system (RES),
      resulting in not only neutralization of potential MNP toxicity but also reduced
      circulation time necessary for MNP efficacy. We discuss the role of MNP size,
      composition and surface chemistry in their intracellular uptake, biodistribution,
      macrophage recognition and cytotoxicity, and review current studies on MNP
      toxicity, caveats of nanotoxicity assessments and engineering strategies to
      optimize MNPs for biomedical use.

PMID- 19389437
TI  - Regulatory perspective on the importance of ADME assessment of nanoscale material
      containing drugs.
AB  - The promise of nanoscale material containing drug products to treat complex
      diseases is mounting. According to the literature, in addition to the liposomes,
      micelles, emulsions, there are novel drug delivery systems such as dendrimers and
      metal colloids at different stages of pre-clinical and clinical development. With
      the anticipation that more nanoscale material containing drug products will be
      submitted to the Food and Drug Administration (FDA) for approval in the future,
      FDA formed a Nanotechnology Task Force in 2006 to determine the critical
      regulatory issues regarding nanomaterials. As a result, all centers within the
      FDA are considering the development of guidance documents to address nanomaterial
      specific issues. It is well established in the literature that physico-chemical
      characterization (PCC) studies are crucial for nanomaterial containing drug
      products. However, this paper addresses the equally important topic of
      Absorption, Distribution, Metabolism and Excretion (ADME) studies for
      nanomaterials and provides examples of how physical properties affect
      biodistribution (i.e. the state of agglomeration, or aggregation, surface
      characteristics, stability of PEG). This paper also attempts to highlight some of
      the ADME study design issues related to nanomaterials such as the need for
      conducting biodistribution studies on each moiety of the multifunctional
      nanoparticles, dual labeled pharmacokinetic (PK) studies, and comparative PK
      studies on the free versus encapsulated drugs. In addition, this paper underlines
      the importance of long-term biodistribution and mass balance studies to
      understand the nanoparticle accumulation profile which may help to assess the
      safety and efficacy of the nanomaterial containing drug products. This review
      also lists some of the pre-clinical guidance documents that may help sponsors get
      started in developing data for inclusion in an initial investigational new drug
      application package for nanoscale material containing drug products.

PMID- 19389438
TI  - Gene regulation for effective gene therapy. Preface.

PMID- 19389439
TI  - Relationship between diet-induced changes in body fat and appetite sensations in
      women.
AB  - To quantify the impact of weight/fat loss on appetite sensations, 54 overweight
      women followed a caloric restriction program (-2900 kJ/day). Their body
      composition and appetite sensations were assessed. Visual analogue scales (VAS)
      were used to measure desire to eat, hunger, fullness and prospective food
      consumption. The results showed that there is a significant association between
      the decrease in body fat mass and the change in appetite sensations, predicting a
      5.8-mm increase in desire to eat and a 3.6-mm decrease in fullness per kg fat
      loss. This quantified relationship could serve as a reference point to evaluate
      the satiating efficiency of functional foods when they are combined with a weight
      reducing program.

PMID- 19389440
TI  - Packaging limits and stability of HIV-1 sequences in a coxsackievirus B vector.
AB  - Enteroviruses elicit protective mucosal immune responses that could be harnessed
      as part of a strategy to prevent sexual transmission of the human
      immunodeficiency virus-1 (HIV-1). We report the construction of replication
      competent recombinant vectors of coxsackievirus B3 (CVB3) that express one or
      more portions of the HIV-1 Gag protein. Vectors containing the capsid domain of
      Gag were initially genetically unstable with protein expression lost after brief
      passage in tissue culture. Codon modification to increase the G/C content of the
      HIV-1 capsid sequence resulted in enhanced genetic stability of CVB3 vectors
      during in vitro passage. Cells infected with a vector expressing the matrix (MA)
      subunit of the HIV-1 Gag protein were susceptible to lysis by CD8 T cell clones
      specific for the SL9 epitope found within MA. These studies suggest that CVB3
      vectors may be useful as vaccine vector candidates, if hurdles in class I antigen
      presentation and stability can be overcome.

PMID- 19389441
TI  - An in vivo protective response against toxic effects of the dermonecrotic protein
      from Loxosceles intermedia spider venom elicited by synthetic epitopes.
AB  - Loxoscelism is a necrotic-hemolytic syndrome caused by bites of brown spiders
      belonging to the genus Loxosceles. Many approaches for the treatment of
      Loxosceles poisoning have already been proposed, among which administration of
      specific antivenom is thought to be the more specific. We have evaluated the use
      of peptides as immunogen to raise in rabbits an antibody response that could
      protect animals from a challenge by the Loxtox isoform LiD1, one of the main
      toxic component of Loxosceles intermedia venom. Six antigenic regions of LiD1
      were mapped by using the SPOT method. The corresponding peptides were further
      chemically synthesized, mixed, and used as immunogens in rabbits. Control animal
      received recombinant LiD1 alone or together with peptides. We found that the
      rabbit antibody response to peptides was cross-reactive with LiD1, although only
      one peptide from the mix of six was immunogenic. The dermonecrotic, hemorrhagic
      and oedema forming activities induced by LiD1 in naive rabbits were inhibited by
      82%, 35% and 35% respectively, by preincubation of LiD1 with anti-peptide
      antibodies prepared from immunized rabbits. Animals that were immunized with
      peptides or LiD1r, were found to be protected from the dermonecrotic, hemorrhagic
      and oedema forming activities induced by a challenge with LiD1. The protection
      conferred by peptides was, however, lower than that provided by the peptide
      protein combination or by the full-length protein. These results encourage us in
      the utilization of synthetic peptides for therapeutic serum development or
      vaccination approaches.

PMID- 19389442
TI  - Influenza vaccination uptake and socioeconomic determinants in 11 European
      countries.
AB  - BACKGROUND: The objective of this study was to assess the predictive effects of
      socioeconomic factors to explain influenza vaccination coverage rates in 11
      European countries. METHODS: Data from national household surveys collected over
      up to seven consecutive seasons between 2001/2002 and 2007/2008 were analyzed to
      assess the associations of socioeconomic factors with immunization against
      influenza. RESULTS: In total, data from 92,101 household contacts representative
      for the national non-institutionalized population aged above 14 years were
      analyzed. Influenza vaccination coverage rates in Europe remain suboptimal with
      little or no progress in the last years. The results of this study indicate that
      gender, household income, size of household, educational level and population
      size of living residence may significantly contribute to explain chances of
      getting immunized against influenza apart from the known risk factors age and
      chronic illness. The effect of these socioeconomic factors was differently
      expressed among the countries and could not be explained solely on basis of
      economic characteristics of these countries. CONCLUSIONS: Future measures should
      address inequalities to achieve the WHO target by 2010 with an influenza
      vaccination rate of 75% in the elderly. National vaccination campaigns may need
      to take socioeconomic segments of the population here identified as less likely
      of getting the influenza vaccine into account.

PMID- 19389444
TI  - Preoperative vaccination for HBV at Polish hospitals as a possible public health
      tool to limit the spread of the epidemic: a cross-sectional study.
AB  - To determine the immunisation coverage for HBV and the prevalence of HBsAg an
      anonymous serosurvey of consecutive adult surgical/gynaecologic patients
      presenting to 16 randomly selected hospitals in West Pomerania, Poland, was
      conducted. Immunisation rate was 60.4%, of these 69.7% had received the complete
      course of three doses; 65.2% were immunised at the request of referring surgeons.
      The multivariable regression model revealed that age <40 years, low educational
      status, not having a surgery in the past, tattoo application, and emergency
      procedure were each associated with a greater odds of not being vaccinated. HBsAg
      prevalence was 0.6%. Authors conclude that the preoperative vaccination policy
      might be an effective public health tool to limit the spread of the epidemic.

PMID- 19389443
TI  - A live guinea pig cytomegalovirus vaccine deleted of three putative immune
      evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge
      model of congenital cytomegalovirus infection.
AB  - Live attenuated vaccines for prevention of congenital cytomegalovirus infections
      encode numerous immune evasion genes. Their removal could potentially improve
      vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC
      class I homologs (presumed NK evasins) were deleted from the guinea pig
      cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live
      attenuated vaccine in the guinea pig congenital infection model. 3DX was
      attenuated in vivo but not in vitro. Vaccination with 3DX produced elevated
      cytokine levels and higher antibody titers than wild type (WT) virus while
      avidity and neutralizing titers were similar. Protection, assessed by maternal
      viral loads and pup mortality following pathogenic viral challenge during
      pregnancy, was comparable between 3DX and WT and significant compared to naive
      animals. These results suggest that the safety and perhaps efficacy of live
      attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral
      immunomodulatory genes.

PMID- 19389445
TI  - Pulmonary delivery of DNA encoding Mycobacterium tuberculosis latency antigen
      Rv1733c associated to PLGA-PEI nanoparticles enhances T cell responses in a DNA
      prime/protein boost vaccination regimen in mice.
AB  - During persistent infection and hypoxic-stress, Mycobacterium tuberculosis (Mtb)
      expresses a series of Mtb latency antigens. The aim of this study was to evaluate
      the immunogenicity of a DNA vaccine encoding the Mtb latency antigen Rv1733c and
      to explore the effect of pulmonary delivery and co-formulation with poly (d,l
      lactide-co-glycolide) (PLGA)-polyethyleneimine (PEI) nanoparticles (np) on host
      immunity. Characterization studies indicated that PLGA-PEI np kept their
      nanometer size after concentration and were positively charged. The np were able
      to mature human dendritic cells and stimulated them to secrete IL-12 and TNF
      alpha comparable to levels observed after lipopolysaccharide (LPS) stimulation.
      Mtb latency antigen Rv1733c DNA prime combined with Rv1733c protein boost
      enhanced T cell proliferation and IFN-gamma secretion in mice in response to
      Rv1733c and Mtb hypoxic lysate. Rv1733c DNA adsorbed to PLGA-PEI np and applied
      to the lungs increased T cell proliferation and IFN-gamma production more
      potently compared to the same vaccinations given intramuscularly. The strongest
      immunogenicity was obtained by pulmonary priming with np-adsorbed Rv1733c DNA
      followed by boosting with Rv1733c protein. These results confirm that PLGA-PEI np
      are an efficient DNA vaccine delivery system to enhance T cell responses through
      pulmonary delivery in a DNA prime/protein boost vaccine regimen.

PMID- 19389446
TI  - Identification of conserved erythrocyte binding regions in members of the
      Plasmodium falciparum Cys6 lipid raft-associated protein family.
AB  - Detergent-resistant lipid raft membrane-associated Pf12, Pf38 and Pf41 proteins
      belong to the Cys(6) family, whose members are implicated in Plasmodium
      falciparum invasion to erythrocytes. We have analyzed the interaction between 20
      mer-long synthetic peptides spanning the entire Pf12, Pf38 and Pf41 sequences and
      erythrocytes. Eight high-activity binding peptides (HABPs) were identified in
      these proteins, which presented saturable bindings susceptible to erythrocytes'
      enzymatic treatment, and beta-turn, random coil and alpha-helical elements as
      principal structural features. Some of these HABPs inhibited merozoite invasion
      in vitro, suggesting a possible role of Pf12, Pf38 and Pf41 during erythrocyte
      invasion and supporting their inclusion in the design of a fully effective
      antimalarial vaccine.

PMID- 19389448
TI  - Pneumococcal vaccination in developing countries: where does science end and
      commerce begin?
AB  - Recently Pneumococcal vaccines have generated considerable interest in developing
      countries as an intervention for protecting children from pneumonia and thereby
      reducing childhood mortality. Many convincing scientific arguments have been put
      forward, although they are often based either on extension of information from
      developed countries, or estimation plus extrapolation of limited local data. In
      addition, there is also significant commercial pressure to prescribe/recommend
      Pneumococcal vaccine(s). Against such a background, it is important for
      developing countries to critically appraise the issues involved in order to make
      a rational choice. This brief paper explores these issues, showing that the
      current Pneumococcal vaccines have limited effectiveness in developing countries
      and the hype surrounding them is more commercial than scientific.

PMID- 19389447
TI  - Acceptance of the HPV vaccine among women, parents, community leaders, and
      healthcare providers in Ohio Appalachia.
AB  - To assess HPV vaccine acceptability, focus groups of women (18-26 years),
      parents, community leaders, and healthcare providers were conducted throughout
      Ohio Appalachia. Themes that emerged among the 23 focus groups (n=114) about the
      HPV vaccine were: barriers (general health and vaccine specific), lack of
      knowledge (cervical cancer and HPV), cultural attitudes, and suggestions for
      educational materials and programs. Important Appalachian attitudes included
      strong family ties, privacy, conservative views, and lack of trust of outsiders
      to the region. There are differences in HPV vaccine acceptability among different
      types of community members highlighting the need for a range of HPV vaccine
      educational materials/programs to be developed that are inclusive of the
      Appalachian culture.

PMID- 19389449
TI  - Induction of Staphylococcus aureus-specific IgA and agglutination potency in milk
      of cows by mucosal immunization.
AB  - Lactating cows were immunized with inactivated Staphylococcus aureus strains and
      concentrated culture supernatants. Application of a repeated mucosal immunization
      scheme resulted in significant levels of S. aureus-specific IgA in milk of dairy
      cows. Average IgA titers against whole cell S. aureus increased during the first
      10 weeks of immunization after which a plateau level was reached and maintained
      during lactation. Immune whey agglutinated both bovine and human S. aureus
      strains including methicillin-resistant S. aureus (MRSA) strains and recognized
      extracted S. aureus proteins on Western blot. ELISAs to quantify milk IgA
      reactive with a number of S. aureus virulence proteins (e.g. enterotoxins,
      microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) and
      immune modulating proteins) and cell wall components, demonstrated the
      polyclonality of the IgA. Correlations observed between agglutination and
      specific IgA titers for whey and for purified IgA suggested functionality of the
      induced antibodies. Milk from immunized cows may provide a way of producing
      potentially therapeutic polyclonal antibodies against S. aureus colonization and
      infection.

PMID- 19389450
TI  - Novel polysaccharide adjuvant from the roots of Actinidia eriantha with dual Th1
      and Th2 potentiating activity.
AB  - The plant polysaccharides are recognized as an effective biological response
      modifier with low toxicity. In this study, the water-soluble polysaccharide from
      the roots of Actinidia eriantha (AEPS) was evaluated for its toxicity and
      adjuvant potential on the specific cellular and humoral immune responses to
      ovalbumin (OVA) in mice. AEP did not cause any mortality and side effects when
      mice were administered subcutaneously twice at the dose up to 5.0mg at intervals
      of 7 days. The mice were immunized subcutaneously with OVA 100 microg alone or
      with OVA 100 microg dissolved in saline containing Quil A (10 microg) or AEPS
      (25, 50, or 100 microg) on days 1 and 15. Two weeks later, splenocyte
      proliferation, natural killer (NK) cell activity, production and mRNA expression
      of cytokines from splenocytes, and serum OVA-specific antibody titers were
      measured. The Con A-, LPS-, and OVA-induced splenocyte proliferation and the
      serum OVA-specific IgG, IgG1, IgG2a, and IgG2b antibody titers in the immunized
      mice were significantly enhanced by AEPS (P<0.05, P<0.01 or P<0.001). AEPS also
      significantly promoted the production of Th1 (IL-2 and IFN-gamma) and Th2 (IL-10)
      cytokines and up-regulated the mRNA expression of IL-2, IFN-gamma, IL-4 and IL-10
      cytokines and T-bet and GATA-3 transcription factors in splenocytes from the
      immunized mice (P<0.05, P<0.01 or P<0.001). Besides, AEPS remarkably increased
      the killing activities of NK cells from splenocytes in the immunized mice (P<0.01
      or P<0.001). The results indicated that AEPS had strong potential to increase
      both cellular and humoral immune responses and elicit a balanced Th1/Th2
      response, and that AEPS may be a safe and efficacious adjuvant candidate suitable
      for a wide spectrum of prophylactic and therapeutic vaccines.

PMID- 19389451
TI  - The first clinical use of a live-attenuated Listeria monocytogenes vaccine: a
      Phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the
      cervix.
AB  - Invasive carcinoma of the cervix (ICC) is the second most common cancer in women
      worldwide. Lm-LLO-E7 vaccine is a live-attenuated Listeria monocytogenes (Lm)
      that secretes the HPV-16 E7 antigen fused to a non-hemolytic fragment of the Lm
      protein listeriolysin O (LLO). In this Phase I trial, the safety of Lm-LLO-E7 was
      assessed in 15 patients with previously treated metastatic, refractory or
      recurrent ICC. Patients received 1 of 3 dose levels of Lm-LLO-E7 (1 x 10(9)CFU,
      3.3 x 10(9)CFU or 1 x 10(10)CFU) as an intravenous infusion, followed by a second
      dose 3 weeks later. All patients experienced a flu-like syndrome which responded
      to non-prescription symptomatic treatment. Severe (grade 3) adverse events
      related to Lm-LLO-E7 were reported in 6 patients (40%), but no grade 4 adverse
      events were observed. At the highest dose some patients had severe fever and dose
      limiting hypotension. By the end of the study protocol, 2 patients had died, 5
      had progressed, 7 had stable disease and 1 qualified as a partial responder. This
      study shows for the first time that a live-attenuated Lm is safe to be
      administered to late stage ICC patients.

PMID- 19389452
TI  - Impact of transmission dynamics on the cost-effectiveness of rotavirus
      vaccination.
AB  - The objective of this study is to estimate the cost-effectiveness of mass
      vaccination of US infants with the recently available rotavirus vaccine, RotaTeq.
      We developed a dynamic transmission model of rotavirus to incorporate herd
      immunity into cost-effectiveness analysis. Our study indicates that a rotavirus
      vaccination program would prevent about 90% of rotavirus incidence, mortality,
      hospitalization and emergency department visits annually. We conclude that a
      universal rotavirus vaccine program in the US would cost $77.30 per case averted
      from the health care and give a net saving of $80.75 per case averted from the
      societal perspectives, respectively. The cost per QALY gained was found to be
      $104,610 when we considered child with one caregiver, making the rotavirus
      vaccination program a cost-effective intervention.

PMID- 19389453
TI  - Human immunodeficiency virus-like particles with consensus envelopes elicited
      broader cell-mediated peripheral and mucosal immune responses than polyvalent and
      monovalent Env vaccines.
AB  - Envelope (Env) sequences from human immunodeficiency virus (HIV) strains can vary
      by 15-20% within a single clade and as much as 35% between clades. Previous AIDS
      vaccines based upon a single isolate often could not elicit protective immune
      responses against heterologous viral challenges. In order to address the vast
      sequence diversity in Env sequences, consensus sequences were constructed for
      clade B and clade C envelopes and delivered to the mouse lung mucosa on the
      surface of virus-like particles (VLP). Consensus sequences decrease the genetic
      difference between the vaccine strain and any given viral isolate. The elicited
      immune responses were compared to a mixture of VLPs with Envs from primary viral
      isolates. This polyvalent vaccine approach contains multiple, diverse Envs to
      increase the breadth of epitopes recognized by the immune response and thereby
      increase the potential number of primary isolates recognized. Both consensus and
      polyvalent clade B Env VLP vaccines elicited cell-mediated immune responses that
      recognized a broader number of clade B Env peptides than a control monovalent Env
      VLP vaccine in both the systemic and the mucosal immune compartments. All three
      clade C Env vaccine strategies elicited similar responses to clade C peptides.
      However, both the consensus B and C Env VLP vaccines were more effective at
      eliciting cross-reactive cellular immune responses to epitopes in other clades.
      This is the first study to directly compare the breadth of cell-mediated immune
      responses elicited by consensus and polyvalent Env vaccines.

PMID- 19389454
TI  - Neuropsychological functions and metabolic aspects in subclinical hypothyroidism:
      the effects of L-thyroxine.
AB  - Thyroid hypofunction is a slowly progressing graded phenomenon [Vanderpump MP,
      Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The incidence of
      thyroid disorders in the community: a twenty-year follow-up of the Whickham
      Survey. Clin Endocrinol (Oxf) 1995;43(1):55-68]; subclinical forms (SCH) often
      represent a laboratory diagnosis in apparently asymptomatic patients. In the
      absence of adequate parameters for thyroid hormone action in tissues, the level
      of TSH increase corresponding to negative effects remains unsettled. We studied a
      wide range of physiological processes in a strictly selected population of 38
      female patients (56.4+/-12.6 years) with minor forms of SCH (TSH 6.6+/-1.8
      mIU/L), after exclusion of neurological, psychiatric and somatic disorders or
      confounding conditions. The investigations, performed at admission and after 6
      months of l-thyroxine (LT4) treatment, included metabolic evaluation, health
      status perception and an extensive battery of neuropsychological tests and
      psychological rating scales. Lipid metabolism improved after LT4 (total
      cholesterol: 231.9+/-49.6 mg/dl pre- vs 221.0+/-40.0 mg/dl post-treatment; LDL
      cholesterol: 183.1+/-62.9 vs 162.7+/-53.7 mg/dl; apolipoprotein A1: 183.5+/-64.5
      vs 160.9+/-50.3 mg/dl; p<0.05 for all comparisons), while glucose metabolism was
      unchanged. Health status perception was favourably influenced by the treatment
      (total SF-36 score 97.8+/-18.4 pre- vs 108.5+/-14.8 post-, p<0.0001); in a
      matched control group with euthyroid goiter, tested to examine the effects of
      medical care in the absence of treatment, no significant differences were found
      in the SF-36 scores at admission and after 6 months (109.3+/-15.1 vs 109+/-14.2,
      p=0.9). Attention performance improved after LT4; HRSD and HRSA scores did not
      significantly change, but negative correlations were found between FT3 levels and
      affective scores at admission, and between the post-treatment changes of
      affective scores and of FT3. In our study subtle disturbances of health status
      perception, attention and lipid metabolism associated to SCH of mildest degrees
      were reverted by LT4 replacement, reinforcing reports of unfavourable
      consequences of marginal thyroid disease.

PMID- 19389455
TI  - Effects of childhood trauma on HPA-axis reactivity in women free of lifetime
      psychopathology.
AB  - Exposure to childhood trauma may induce persistent changes in Hypothalamic
      Pituitary-Adrenal (HPA)-axis functioning even in the absence of current
      psychopathology. Because previous studies did not systematically exclude subjects
      with lifetime psychiatric morbidity, prevalent psychopathology may have
      confounded the association. In this study we investigated whether women exposed
      to childhood trauma, but without a history of psychiatric disorders, show
      alterations in HPA-axis functioning. We included 10 women exposed to significant
      childhood trauma and 12 non-exposed women. All women were between 29 and 64 years
      old,mentally and physically healthy, and without current or lifetime
      psychopathology. HPA-axis functioning was assessed as 1) basal activity with
      salivary cortisol patterns over 8 time points on two consecutive sampling days
      and 2) plasma cortisol and adrenocorticotropic hormone (ACTH) reactivity over 7
      time points after the combined dexamethasone/corticotropin-releasing hormone
      (dex/CRH) challenge test. Basal salivary cortisol output did not differ between
      trauma-exposed compared to non-exposed women. Significantly blunted plasma
      cortisol and ACTH responses in response to dex/CRH administration were found in
      the trauma exposed compared to the non-exposed women (F(1,20)=5.08, p=0.04 and
      F(1,20)=5.23, p=0.03 respectively). Adjusting for age, body mass index (BMI),
      oral contraceptive use, and menopausal status,somewhat weakened the associations
      for cortisol as well as ACTH (F(1,16)=3.30, p=0.09) and F(1,16)=2.17, p=0.16
      respectively), but for cortisol absolute differences in point estimates were
      largely unaffected.Although basal cortisol patterns were similar in the two
      groups, exposure to childhood trauma seemed to be related to a blunted HPA-axis
      reactivity in women who were free of current or lifetime psychopathology.

PMID- 19389456
TI  - Decreased density of serotonin 2A receptors in the superior temporal gyrus in
      schizophrenia--a postmortem study.
AB  - The superior temporal gyrus (STG) is strongly implicated in the pathophysiology
      of schizophrenia, particularly with regards to auditory hallucinations. In this
      study, using in situ quantitative autoradiography in postmortem tissue, we
      investigated the binding of the [3H]ketanserin to 5-HT(2A) receptors and
      [3H]mesulergine to 5-HT(2C) receptors in the left STG of 8 male schizophrenic
      patients compared to 8 control subjects. A strong [3H]ketanserin binding was
      observed in the STG, however there was a very weak [3H]mesulergine binding in the
      STG. A significant decrease in binding of [(3)H]ketanserin was clearly observed
      in schizophrenia patients in comparison with control subjects. There were no
      significant correlations between 5-HT(2A) binding density and age, postmortem
      intervals, or brain pH. These results suggest that the alterations of the 5
      HT(2A) receptors contribute to the pathophysiology of the STG in schizophrenia.
      Furthermore, there is a clear tendency for a positive correlation between 5
      HT(2A) and muscarinic M1 receptor bindings, and for negative correlations between
      5-HT(2A) and GABA(A) receptor bindings and between muscarinic M1 and GABA(A)
      receptor bindings. This provides a possible mechanism of auditory hallucinations
      through interactions between 5-HT(2A), acetylcholine muscarinic and GABA
      transmissions in the STG in schizophrenia.

PMID- 19389457
TI  - The septo-hippocampal system, learning and recovery of function.
AB  - We understand this review as an attempt to summarize recent advances in the
      understanding of cholinergic function in cognition. Such a role has been
      highlighted in the 1970s by the discovery that dementia patients have greatly
      reduced cholinergic activity in cortex and hippocampus. A brief anatomical
      description of the major cholinergic pathways focuses on the basal forebrain and
      its projections to cortex and hippocampus. From this distinction, compelling
      evidence suggests that the basal forebrain --> cortex projection regulates the
      excitability of principal cortical neurons and is thereby critically involved in
      attention, stimulus detection and memory function, although the biological
      conditions for these functions are still debated. Similar uncertainties remain
      for the septo-hippocampal cholinergic system. Although initial lesions of the
      septum caused memory deficits reminiscent of hippocampal ablations, recent and
      more refined neurotoxic lesion studies which spared non-cholinergic cells of the
      basal forebrain failed to confirm these memory impairments in experimental
      animals despite a near total loss of cholinergic labeling. Yet, a decline in
      cholinergic markers in aging and dementia still stands as the most central piece
      of evidence for a link between the cholinergic system and cognition and appear to
      provide valuable targets for therapeutic approaches.

PMID- 19389459
TI  - Aflatoxin M1 contamination in pasteurized milk in Tabriz (northwest of Iran).
AB  - Aflatoxin M1 (AFM1) appears in milk as a direct result of the ingestion of food
      contaminated with aflatoxin B1 by cattle. The role of milk in human nutrition is
      well-known. The aim of this study was to evaluate Aflatoxin M1 contamination in
      pasteurized milk samples in Tabriz city (Iran) by ELISA (Enzyme Linked
      Immunosorbent Assay). Fifty pasteurized milk samples from different supermarkets
      in Tabriz city were collected during 6 months (July to December 2008). AFM1 was
      found in 100% of the examined milk samples. Sixty-two percent of the samples had
      AFM1 greater than the maximum tolerance limit (50 ng/l) accepted by European
      Union. It can be concluded that AFM1 levels in the samples purchased in Tabriz
      city, appear to be a serious public health problem at the moment. To achieve a
      low level of AFM1 in milk, dairy cows' feed samples from various cows' herds must
      be controlled periodically for aflatoxin and kept away from fungal contamination
      as much as possible.

PMID- 19389458
TI  - Effect of processing on folic acid fortified Baladi bread and its possible effect
      on the prevention of colon cancer.
AB  - This paper studied the possible effect of folic acid in fortified Baladi bread on
      the prevention of colon cancer development in rats. Wheat flour samples (82%
      extraction rate) and soy bean flour were analyzed to determine their folic acid
      contents using the High Performance Liquid Chromatography (HPLC). Unfortified and
      folic acid fortified Baladi breads were prepared. Samples from each step of bread
      preparation were analyzed for folic acid concentration. Protein, fat, ash, fibers
      and carbohydrates percentages were also determined. Rats were divided into five
      groups, four of them were injected subcutaneously with dimethylhydrazine (DMH).
      After 15 weeks, the rats were sacrificed for pathological examination. Results
      showed that the folic acid content in wheat flour (82% extraction rate) was found
      to be highly significantly lower than that in soybean flour. After baking, folic
      acid content in all breads was found to decrease significantly. The highest
      protein and fat contents were found in soybean flour fortified Baladi bread. The
      colons of rats of groups 3 (fed 5% soy flour fortified Baladi bread) and 5 (fed
      Baladi bread fortified with 5% soy flour+8 mg folic acid/kg wheat flour) were the
      mostly affected by DMH injection as premalignant changes were observed.

PMID- 19389460
TI  - Non-genomic signaling by steroids.

PMID- 19389461
TI  - Specificity protein-1 and -3 trans-activate the ovine placental lactogen gene
      promoter.
AB  - The proximal promoter (-383/+16) of the ovine placental lactogen (oPL) gene
      provides trophoblast-specific expression in vitro. Footprint 6 (FP6; -319/-349)
      lies within this region, and transfection of two-base pair mutations across FP6
      into BeWo cells identified potential binding sites for CCAAT-enhancer binding
      protein (CEBP) and specificity proteins (Sp). Transfection of CEBP dominant
      negative or over-expression constructs did not impact transactivation of the
      proximal promoter. However, Sp1 and Sp3 over-expression constructs increased
      (p<or=0.05) transactivation. Additionally, Sp1 and Sp3 short-hairpin RNA
      constructs reduced (p<or=0.01) transactivation of the proximal promoter. In EMSA
      supershift assays, Sp1 and Sp3 antibodies were able to inhibit migration of the
      complexes formed with nuclear extracts from BeWo cells and ovine chorionic
      binucleate cells (oBNC). Furthermore, Southwestern analysis of oBNC nuclear
      extracts identified a nuclear protein corresponding with Sp3, identified by
      Western analysis. In conclusion, these results indicate that Sp1 and Sp3 are
      capable of interacting with FP6 of the oPL gene proximal promoter and function to
      enhance its transactivation.

PMID- 19389462
TI  - The effects of acetaldehyde on nicotine-induced transmitter levels in young and
      adult brain areas.
AB  - The aim of the present study was to examine the effect of acetaldehyde
      administration on neurotransmitters in the presence of nicotine in brain areas
      associated with cognition and reward. We assayed these effects via microdialysis
      in conscious freely moving male Sprague-Dawley rats. It was reported that low
      doses of acetaldehyde enhance nicotine self-administration in young, but not in
      adult rats. Since nicotine enhances reward and learning, while acetaldehyde is
      reported to enhance reward but inhibit learning, acetaldehyde thus would be
      likely to stimulate reward without stimulating learning. We hoped that examining
      the effects of acetaldehyde (on nicotine-mediated neurotransmitter changes) would
      help to distinguish reward mechanisms less influenced by learning mechanisms. To
      avoid the aversive effect of acetaldehyde, we used a low dose of acetaldehyde
      (0.16 mg/kg) administered after nicotine (0.3mg/kg). We analyzed six brain
      regions: nucleus accumbens shell (NAccS), ventral tegmental area (VTA), ventral
      and dorsal hippocampus (VH and DH), and prefrontal and medial temporal cortex
      (PFC, MTC), assaying dopamine (DA), norepinephrine (NE) and serotonin (5-HT) and
      their metabolites in young and adult rats. The effect of acetaldehyde on nicotine
      induced transmitter changes was different in young as compared to adult rat brain
      regions. In the NAccS of the young, DA was not affected while NE and 5-HT were
      increased. In the adult in this area DA and NE were decreased, while 5-HT was not
      altered. In other areas also in many cases, the effect of acetaldehyde in the
      young and in the adult was different. As an example, acetaldehyde administration
      increased NE in young and decreased NE in adult DH. We found stimulation of
      nicotine-induced changes by acetaldehyde in seven instances - six of these were
      observed in areas in young brain, NE in four areas (NAccS, DH, VH, and PFC), and
      5-HT in two (NAccS and DH). Only one increase was noted in adult brain (DA in
      VTA). Inhibition of nicotine-induced changes by acetaldehyde was noticed in four
      young brain areas (DA in PFC and MTC, 5-HT in VTA, and VH) and in 13 adult brain
      areas (DA in NAccS, DH, VH, PFC, MTC, NE in NAccS, DH, PFC, MTC, and 5-HT in DH,
      VH, MTC, and PFC). Thus acetaldehyde was more stimulatory in young and more
      inhibitory in the adult brain areas tested, which could explain its stimulating
      nicotine reward only in young animals. That increases in NE were noted only in
      young, decreases in NE only in adult brain areas further suggest the role of NE
      in the age-dependent response. In general, six areas showed some increase and
      four showed decrease in the young versus one showing increase and thirteen
      showing decrease in the adult. Clearly the effects of acetaldehyde in young
      animals are different from those in adult animals. Because acetaldehyde did not
      induce elevated DA levels in the NAccS of the young, we believe that the higher
      reward in the young caused by acetaldehyde is not likely due to DA changes in the
      accumbens. The increase of NE and 5-HT in the brain areas of the young only
      raises the possibility that they may play an important role in reward in some
      cases when DA in the accumbens does not. Areas involved in cognitive mechanisms
      and a number of transmitters seem to play a role in reward stimulation.

PMID- 19389463
TI  - Dogs in Pavlov's laboratory.

PMID- 19389464
TI  - Stimulus discrimination by horses under scotopic conditions.
AB  - Scotopic vision in horses (Equus caballus) was investigated using behavioral
      measurements for the first time. Four horses were tested for the ability to make
      simple visual discriminations of geometric figures (circles and triangles) under
      various brightness levels within an enclosed building. Measurements of brightness
      ranging from 10.37 to 24.12 magnitudes per square arcsecond (mag/arcsec(2); in
      candelas per square meter-7.70 to 2.43E-05cd/m(2)) were taken using a Sky Quality
      Meter. These values approximated outdoor conditions ranging from twilight in open
      country to a dark moonless night in dense forest. The horses were able to solve
      the discrimination problems in all brightness settings up to 23.77mag/arcsec(2)
      (3.35E-05cd/m(2)). Moreover, they easily navigated their way around obstacles
      located within the testing area in extremely dim light (>23.50mag/arcsec(2);
      4.30E-05cd/m(2)), which were in conditions too dark for the human experimenters
      to see. These findings support physiological data that reveal a rod-dominated
      visual system as well as observations of equine activity at night.

PMID- 19389465
TI  - The ovine urokinase plasminogen activator and its receptor cDNAs: molecular
      cloning, characterization and expression in various tissues.
AB  - The activation of plasminogen plays a crucial role in a variety of extracellular
      proteolytic events such as, fibrinolysis, cell migration, ovulation, involution
      of the mammary gland and the activation of other protease classes and growth
      factors. In this paper we describe the isolation of the full-length cDNAs of
      ovine urokinase plasminogen activator (u-PA) and its receptor (u-PAR) using a
      polymerase chain reaction based strategy. The ovine u-PA cDNA comprised of 2350
      bp and it is characterized by a coding region of 1302 bp, and 5'- and 3'-UTR
      regions of 129 and 919 bp, respectively. The deduced amino acid sequence consists
      of 433 amino acids. The ovine u-PAR cDNA is comprised of 1247 bp and it is
      characterized by a coding region of 957 bp and 5'- and 3'-UTR regions of 44 and
      246 bp respectively. The deduced amino acid sequence consists of 318 amino acids.
      Three-dimensional models of the putative protein products of both cDNAs showed
      that the proteins bear a high similarity with their human counterparts. Real-time
      PCR revealed high levels of u-PA expression in the adipose tissue, followed by
      that in mammary gland and kidney. Lower levels of expression were detected in the
      adrenal glands, heart, ovaries, spleen, liver and cerebellum. A similar pattern
      was observed in u-PAR expression with noticeably lower levels of expression in
      heart, liver and cerebellum. To the best of our knowledge, this is the first
      paper reporting expression of u-PA and u-PAR in the adipose tissue. These data
      strengthen the suggestion that adipose tissue functions as an endocrine organ
      besides an energy storage organ. Furthermore, u-PA and u-PAR mRNA levels were 7
      and 8.5 fold higher respectively in involuting mammary tissue obtained from non
      lactating ewes compared to that detected in mammary tissue obtained from
      lactating ewes. These data are consistent with the notion that upregulation of u
      PA and u-PAR expression may play a key role in the process of involution of the
      mammary gland.

PMID- 19389466
TI  - Temporally dynamic frequency tuning of population responses in monkey primary
      auditory cortex.
AB  - Frequency tuning of auditory cortical neurons is typically determined by
      integrating spikes over the entire duration of a tone stimulus. However, this
      approach may mask functionally significant variations in tuning over the time
      course of the response. To explore this possibility, frequency response functions
      (FRFs) based on population multiunit activity evoked by pure tones of 175 or 200
      ms duration were examined within four time windows relative to stimulus onset
      corresponding to "on" (10-30 ms), "early sustained" (30-100 ms), "late sustained"
      (100-175 ms), and "off" (185-235 or 210-260 ms) portions of responses in primary
      auditory cortex (A1) of 5 awake macaques. FRFs of "on" and "early sustained"
      responses displayed a good concordance, with best frequencies (BFs) differing, on
      average, by less than 0.25 octaves. In contrast, FRFs of "on" and "late
      sustained" responses differed considerably, with a mean difference in BF of 0.68
      octaves. At many sites, tuning of "off" responses was inversely related to that
      of "on" responses, with "off" FRFs displaying a trough at the BF of "on"
      responses. Inversely correlated "on" and "off" FRFs were more common at sites
      with a higher "on" BF, thus suggesting functional differences between sites with
      low and high "on" BF. These results indicate that frequency tuning of population
      responses in A1 may vary considerably over the course of the response to a tone,
      thus revealing a temporal dimension to the representation of sound spectrum in
      A1.

PMID- 19389467
TI  - Honey bee (Apis mellifera) workers live longer in small than in large colonies.
AB  - Social insect colonies are highly integrated units that can be regarded in some
      respects as super-organisms, with colony size and individuals analogous to body
      size and cells in unitary organisms. In both, unitary organisms and super
      organisms, the relation between body/colony size and lifespan of the constituent
      units (cells/individuals) is important for understanding systemic aging but
      remains to be explored. Therefore, this study compared the life-history and
      longevity of individual honey bee workers between a large and a small colony
      social environment. We found that individuals in large colonies were consistently
      shorter lived than individuals in small colonies. This experimental effect
      occurred in both principal life history phases of honey bee workers, the in-hive
      and the foraging stage, independently of the age of the workers at their
      transition between the two. Nevertheless, this age of first foraging was a key
      determinant of worker longevity, in accordance with previous studies. The large
      colonies raised more brood, built more comb, and foraged at higher rates. Our
      results do not comply with the idea that social group size has a positive effect
      on individual longevity. Instead, our findings suggest that large and small
      colonies follow different demographic growth trajectories, trading off longevity
      of individuals for overall colony growth. Similarly, multi-cellular organisms
      might sacrifice maintenance and repair of their individual constituent cells for
      enhanced metabolic activity and organismal growth, leading to the widely-observed
      negative correlation between longevity and body size within species.

PMID- 19389468
TI  - Gene expression profiling of resistant and susceptible Bombyx mori strains
      reveals nucleopolyhedrovirus-associated variations in host gene transcript
      levels.
AB  - We investigated variations in the gene expression of Bombyx mori following
      infection with a nucleopolyhedrovirus (BmNPV). Two B. mori strains, KN and 306,
      which are highly resistant and susceptible to BmNPV infection, respectively, were
      used in this study. The infection profiles of BmNPV in the B. mori KN and 306
      larvae revealed that the virus invaded the midguts of both these strains.
      However, its proliferation was notably inhibited in the midgut of the resistant
      strain. By using the suppression subtractive hybridization method, two cDNA
      libraries were constructed in order to compare the BmNPV responsive gene
      expressions between the two silkworm lines. In total, 62 differentially expressed
      genes were obtained. Real-time qPCR analysis confirmed that eight genes were
      significantly up-regulated in the midgut of the KN strain following BmNPV
      infection. Our results imply that these up-regulated genes may be involved in the
      B. mori immune response against BmNPV infection.

PMID- 19389470
TI  - Modulation of Trypanosoma rangeli ecto-phosphatase activity by hydrogen peroxide.
AB  - As a protozoan parasite of hematophagous insects, Trypanosoma rangeli
      epimastigotes are exposed to reactive oxygen species during development in hosts.
      In this work, we investigated the role of H(2)O(2) as a modulator of the ecto
      phosphatase activity present in living T. rangeli. We observed that H(2)O(2)
      inhibits ecto-phosphatase activities in the short and long epimastigote forms of
      T. rangeli. Ecto-phosphatase activity found in the short form was more sensitive
      than that found in the long form. Moreover, H(2)O(2) inhibited ecto-phosphatase
      activity of the short form in a dose-dependent manner and this inhibition was
      reversible after H(2)O(2) removal. This effect was not observed for T. rangeli
      ecto-ATPase, another ecto-enzyme present on the external surface of T. rangeli.
      Cysteine, beta-mercaptoethanol, and reduced glutathione were able to revert the
      enzyme inhibition promoted by H(2)O(2). Catalase and glutathione peroxidase
      stimulated this ecto-phosphatase activity, whereas superoxide dismutase was not
      able to modulate this activity. The ecto-phosphatase activity was also activated
      by FCCP and inhibited by oligomycin. It seems that H(2)O(2) plays a fundamental
      role in the regulation of cellular processes of these organisms. We showed, for
      the first time, that these parasites can produce H(2)O(2), and it is able to
      regulate ecto-phosphatase activity.

PMID- 19389471
TI  - Acute and chronic modulation of placental chorionic plate artery reactivity by
      reactive oxygen species.
AB  - Control of vascular resistance and blood flow in the fetoplacental circulation is
      incompletely understood. Reactive oxygen species (ROS), physiological and
      pathophysiological regulators of vascular tone, are elevated in preeclampsia
      (PE), a disease of pregnancy characterized by increased fetoplacental vascular
      resistance. We tested the hypothesis that ROS modulate vascular reactivity in
      placental chorionic plate arteries. Wire myography was used to examine (1) the
      effects of acute exposure to ROS on arterial function in normal pregnancy and (2)
      the effects of maternal antioxidant supplementation on arterial reactivity in
      women at high risk for PE participating in the Vitamins in Pre-eclampsia (VIP)
      trial. ROS generated by xanthine plus xanthine oxidase enhanced basal tension,
      vasoconstriction in response to the thromboxane mimetic U46619, and relaxation in
      response to sodium nitroprusside. Hydrogen peroxide and peroxynitrite increased
      basal tone and relaxed preconstricted arteries (U44619), respectively. In women
      at risk for PE, chorionic plate artery constriction in response to U46619 was
      greater in the women receiving placebo compared to the women supplemented with
      the antioxidant vitamins C and E. ROS may regulate fetoplacental vascular
      resistance and blood flow in the short term, and chronic exposure to raised ROS
      could contribute to elevated fetoplacental vascular resistance in PE and fetal
      growth restriction (FGR).

PMID- 19389473
TI  - OXPHOS gene expression and control in mitochondrial disorders.
AB  - The cellular consequences of deficiencies of the mitochondrial OXPHOS system
      include a variety of direct and secondary changes in metabolite homeostasis, such
      as ROS, Ca(2+), ADP/ATP, and NAD/NADH. The adaptive responses to these changes
      include the transcriptional responses of nuclear and mitochondrial genes that are
      mediated by these metabolites, control of the mitochondria permeability
      transition pore, and a great variety of secondary signalling elements. Among the
      transcriptional responses reported over more than a decade using material
      harboring mtDNA mutations, deletions, or depletions, nuclear and mitochondrial
      DNA OXPHOS genes have mostly been up-regulated. However, it is evident from the
      limited data in a variety of disease models that expression responses are highly
      diverse and inconsistent. In this article, the mechanisms and controlling
      elements of these transcriptional responses are reviewed. In addition, the
      elements that need to be evaluated, in order to gain an improved perspective of
      the manner in which OXPHOS genes respond and impact on mitochondrial disease
      expression, are highlighted.

PMID- 19389469
TI  - To assess, to control, to exclude: effects of biobehavioral factors on
      circulating inflammatory markers.
AB  - Behavioral scientists have increasingly included inflammatory biology as
      mechanisms in their investigation of psychosocial dynamics on the pathobiology of
      disease. However, a lack of standardization of inclusion and exclusion criteria
      and assessment of relevant control variables impacts the interpretation of these
      studies. The present paper reviews and discusses human biobehavioral factors that
      can affect the measurement of circulating markers of inflammation. Keywords
      relevant to inflammatory biology and biobehavioral factors were searched through
      PubMed. Age, sex, and hormonal status, socioeconomic status, ethnicity and race,
      body mass index, exercise, diet, caffeine, smoking, alcohol, sleep disruption,
      antidepressants, aspirin, and medications for cardiovascular disease are all
      reviewed. A tiered set of recommendations as to whether each variable should be
      assessed, controlled for, or used as an exclusion criteria is provided. These
      recommendations provide a framework for observational and intervention studies
      investigating linkages between psychosocial and behavioral factors and
      inflammation.

PMID- 19389472
TI  - Radioprotective effects of manganese-containing superoxide dismutase mimics on
      ataxia-telangiectasia cells.
AB  - We tested several classes of antioxidant manganese compounds for radioprotective
      effects using human lymphoblastoid cells: six porphyrins, three salens, and two
      cyclic polyamines. Radioprotection was evaluated by seven assays: XTT, annexin V
      and propidium iodide flow cytometry analysis, gamma-H2AX immunofluorescence, the
      neutral comet assay, dichlorofluorescein and dihydroethidium staining, resazurin,
      and colony survival assay. Two compounds were most effective in protecting wild
      type and A-T cells against radiation-induced damage: MnMx-2-PyP-Calbio (a mixture
      of differently N-methylated MnT-2-PyP+ from Calbiochem) and MnTnHex-2-PyP.
      MnTnHex-2-PyP protected WT cells against radiation-induced apoptosis by 58% (p =
      0.04), using XTT, and A-T cells by 39% (p = 0.01), using annexin V and propidium
      iodide staining. MnTnHex-2-PyP protected WT cells against DNA damage by 57% (p =
      0.005), using gamma-H2AX immunofluorescence, and by 30% (p < 0.01), using neutral
      comet assay. MnTnHex-2-PyP is more lipophilic than MnMx-2-PyP-Calbio and is also
      >10-fold more SOD-active; consequently it is >50-fold more potent as a
      radioprotectant, as supported by six of the tests employed in this study. Thus,
      lipophilicity and antioxidant potency correlated with the magnitude of the
      beneficial radioprotectant effects observed. Our results identify a new class of
      porphyrinic radioprotectants for the general and radiosensitive populations and
      may also provide a new option for treating A-T patients.

PMID- 19389474
TI  - Effects of transforming growth factor-beta1 and vascular endothelial growth
      factor 165 gene transfer on Achilles tendon healing.
AB  - Repaired Achilles tendons typically take weeks before they are strong enough to
      handle physiological loads. Gene therapy is a promising treatment for Achilles
      tendon defects. The aim of the present study was to evaluate the
      histological/biomechanical effects of Transforming growth factor-beta1 (TGF
      beta1) and vascular endothelial growth factor 165 (VEGF(165)) gene transfer on
      Achilles tendon healing in rabbits. Bone Marrow-Derived Mesenchymal Stem Cells
      (BMSCs) were transduced with adenovirus carrying human TGF-beta1 cDNA (Ad-TGF
      beta1), human VEGF(165) cDNA (Ad-VEGF(165)), or both (PIRES-TGF-beta1/VEGF(165))
      Viruses, no cDNA (Ad-GFP), and the BMSCs without gene transfer and the intact
      tendon were used as control. BMSCs were surgically implanted into the
      experimentally injured Achilles tendons. TGF-beta1 distribution, cellularity,
      nuclear aspect ratio, nuclear orientation angle, vascular number, collagen
      synthesis, and biomechanical features were measured at 1, 2, 4, and 8 weeks after
      surgery. The TGF-beta1 and TGF beta 1/VEGF(165) co-expression groups exhibited
      improved parameters compared with other groups, while the VEGF(165) expression
      group had a negative impact. In the co-expression group, the angiogenesis effects
      of VEGF(165) were diminished by TGF-beta1, while the collagen synthesis effects
      of TGF-beta1 were unaltered by VEGF(165). Thus treatment with TGF-beta1 cDNA
      transduced BMSCs grafts is a promising therapy for acceleration and improvement
      of tendon healing, leading to quicker recovery and improved biomechanical
      properties of Achilles tendons.

PMID- 19389475
TI  - Anti-CD(45)RB monoclonal antibody induces immunologic toleration by suppressing
      dendritic cells.
AB  - BACKGROUND: In transplantation, the antigen presentation step of T cell
      activation determines whether the T cell rejects the graft, ignores the graft, or
      inhibits other T cells from attacking the graft. Dendritic cells (DCs) are the
      most potent antigen presenting cells that are capable of activating naive T
      cells. The purpose of the present study was to investigate the influence of anti
      CD(45)RB monoclonal antibody on the phenotypes and functions of DCs and to
      further illustrate the mechanism of anti-CD(45)RB monoclonal antibody-inducing
      immunologic tolerance. METHODS: DCs from mice were cultured and treated with
      varying doses of anti-CD(45)RB monoclonal antibody at specific time points.
      Fluorescence-activated cell sorting (FACS) was used to verify the changes of
      phenotypes in the cultured DCs labeled with fluorescent antibody. DCs were also
      used as stimulators in mixed leukocyte reaction to detect their ability to
      stimulate T cell proliferation. RESULTS: Anti-CD(45)RB monoclonal antibody
      induced a dose- and time-dependent suppression of maturation of DCs and a dose
      dependent suppression of T cell proliferation in mixed leukocyte reaction when
      anti-CD(45)RB monoclonal antibody-treated DCs were used as stimulators.
      CONCLUSIONS: One of the mechanisms of anti-CD(45)RB monoclonal antibody-induced
      tolerance was inhibiting maturation and function of DCs and inducing tolerogenic
      DCs to achieve a new immune balance.

PMID- 19389476
TI  - Brain activity preceding a 2D manual catching task.
AB  - We investigated the event-related desynchronization (ERD) and synchronization
      (ERS) properties of cortical EEG rhythms in regions of interest (ROI) during the
      preparation of a 2D task for manual catching of a moving object. EEG signals were
      recorded through a 32-channel system in eleven healthy subjects during the
      interception task consisting of 2D catching with the right hand of a handle
      moving at constant velocity (1.5 m/s) on a predefined straight trajectory. The
      first session of catching movements (CATCHING_PRE) was compared with a second
      session after 1 h with identical characteristics (CATCHING_POST) and with other
      two conditions, where the subjects had to reach and grasp the handle fixed in the
      medium of platform (REACHING) and they looked at the object moving without
      catching it (GAZE TRACKING). Changes of cortical rhythms were correlated with
      dynamic and kinematic indexes of motor performance in both catching sessions.
      Movements requiring different strategies (predictive versus prospective) are
      supported by specific changes of cortical EEG rhythms: in the CATCHING condition
      a more evident power decrease (ERD) in alpha 2 and beta band in the sensorimotor
      region contralateral to the catching hand was observed, while in the REACHING one
      a bilateral ERD in beta band was found. Motor learning and movement
      automatization were characterized by a significant reduction of theta ERS in the
      anterior cingulate cortex (ACC), a ROI linked to focused attention, and with a
      shift of neuronal activation in alpha 2 band from the bilateral superior parietal
      areas to the homologous area of the left hemisphere. Finally, our EEG findings
      are consistent with the role of supplementary motor (SMA), premotor and
      prefrontal areas in motor planning and preparation. In particular, theta ERS in
      left SMA significantly correlated with an improvement of motor performance, as
      evidenced by its correlation with the training-related reduction of interception
      time (IT).

PMID- 19389477
TI  - Skull stripping based on region growing for magnetic resonance brain images.
AB  - In this paper, we propose a new skull stripping method for T1-weighted magnetic
      resonance (MR) brain images. Skull stripping has played an important role in
      neuroimage research because it is a basic preliminary step in many clinical
      applications. The process of skull stripping can be challenging due to the
      complexity of the human brain, variable parameters of MR scanners, individual
      characteristics, etc. In this paper, we aim to develop a computationally
      efficient and robust method. In the proposed algorithm, after eliminating the
      background voxels with histogram analysis, two seed regions of the brain and non
      brain regions were automatically identified using a mask produced by
      morphological operations. Then we expanded these seed regions with a 2D region
      growing algorithm based on general brain anatomy information. The proposed
      algorithm was validated using 56 volumes of human brain data and simulated
      phantom data with manually segmented masks. It was compared with two popular
      automated skull stripping methods: the brain surface extractor (BSE) and the
      brain extraction tool (BET). The experimental results showed that the proposed
      algorithm produced accurate and stable results against data sets acquired from
      various MR scanners and effectively addressed difficult problems such as low
      contrast and large anatomical connections between the brain and surrounding
      tissues. The proposed method was also robust against noise, RF, and intensity
      inhomogeneities.

PMID- 19389478
TI  - Chitosan permeabilizes the plasma membrane and kills cells of Neurospora crassa
      in an energy dependent manner.
AB  - Chitosan has been reported to inhibit spore germination and mycelial growth in
      plant pathogens, but its mode of antifungal action is poorly understood.
      Following chitosan treatment, we characterized plasma membrane permeabilization,
      and cell death and lysis in the experimental model, Neurospora crassa. Rhodamine
      labeled chitosan was used to show that chitosan is internalized by fungal cells.
      Cell viability stains and the calcium reporter, aequorin, were used to monitor
      plasma membrane permeabilization and cell death. Chitosan permeabilization of the
      fungal plasma membrane and its uptake into fungal cells was found to be energy
      dependent but not to involve endocytosis. Different cell types (conidia, germ
      tubes and vegetative hyphae) exhibited differential sensitivity to chitosan with
      ungerminated conidia being the most sensitive.

PMID- 19389479
TI  - Nitric oxide enhances osteoclastogenesis possibly by mediating cell fusion.
AB  - Osteoclasts are multinucleated bone resorbing cells which form by fusion of pre
      osteoclasts. Here, we investigate how nitric oxide (NO) affects
      osteoclastogenesis. Time lapse photomicrography, using the fluorescent NO
      indicator dye, 4,5-diaminofluorescein diacetate, revealed an intense NO signal in
      pre-osteoclasts preceding cell fusion. Osteoclastogenesis in RAW264.7 cells
      increased when exposed to the NO synthase inhibitor, L-NMMA (0.25 microM), for
      the initial 48 h. In contrast, pre-osteoclast fusion decreased when RAW264.7
      cells were exposed to L-NMMA from 48 to 96 h. Both NO synthase inhibitors, L-NMMA
      and L-NAME, decreased osteoclast formation during this time period. The
      inhibitory effect of L-NMMA on osteoclast formation was abolished with increasing
      concentrations (25-200 ng/ml) of sRANKL suggesting signaling cross talk. NO
      donors increased osteoclast formation in a dose-dependent manner, with greatest
      stimulation at 15 microM NOC-12 (2.3 fold) and 5 microM NOC-18 (2.4 fold).
      Measuring nitrite (NO end product) daily from culture media of RAW264.7 cells
      undergoing osteoclastogenesis revealed that an increase in NO production
      coincided with the fusion of pre-osteoclasts (day 4). Inhibiting fusion by
      plating cells on polystyrene dishes pre-coated with poly-(L-lysine) decreased
      both osteoclast formation and NO production. To address if NO mediates fusion
      through the actin cytoskeleton, actin free barbed ends were measured. 0.25 microM
      L-NMMA decreased, while 15 microM NOC-12 and 5 microM NOC-18 increased actin free
      barbed ends. We hypothesize that while NO initially negatively regulates pre
      osteoclast differentiation; it later facilitates the fusion of mononuclear pre
      osteoclasts, possibly by up regulating actin remodeling.

PMID- 19389480
TI  - Identification, mRNA expression and characterization of a novel ANK-like gene
      from Chinese mitten crab Eriocheir japonica sinensis.
AB  - Ankyrins are a family of adapter molecules mediating linkages between integral
      membrane and cytoskeletal proteins. Ankyrin repeat is one of the most frequently
      observed amino acid motifs in protein databases. A novel ANK-like gene of Chinese
      mitten crab Eriocheir japonica sinensis (denoted as EjsANK) was identified and
      cloned by expressed sequence tag and rapid amplification of cDNA end approaches.
      The full-length cDNA of EjsANK is 4375 bp and contains an open reading frame of
      1095 bp which encodes a 364 amino acids polypeptide (40.23 kD) bearing seven
      ankyrin repeats. EjsANK cDNA has a 3073 bp uniquely long 3' untranslated region
      with three K-box elements, one GY-like box domain and one Brd-like box domain.
      Sequence alignment and three-dimensional structural analyses revealed that EjsANK
      should be a novel cytosolic member of the ankyrin family. Fluorescent real-time
      quantitative RT-PCR approach was performed to examine the expression profiles of
      EjsANK mRNA by testing its relative level in three types of tissues at three
      different developmental stages, respectively. We found that the relative level of
      EjsANK mRNA expression was significantly higher in the abdomen at the first crab
      stage. Functional bioinformatics prediction analyses indicated that EjsANK has an
      analogical effect like IkappaB which is a key component of IkappaB/NF-kappaB
      complex in mammalian cells playing very important roles in the development
      process. Results suggest that EjsANK gene is involved in the early developmental
      regulation of Chinese mitten crab, especially brachyurization regulation.

PMID- 19389481
TI  - Molecular cloning and characterization of porcine sirtuin genes.
AB  - The sirtuin family of class III histone deacetylases (HDACs) is named after their
      homology to yeast silent information regulator 2 (SIR2). SIR2 and its mammalian
      derivatives (SIRT1-7) play a central role in gene silencing, cell cycle, aging
      and metabolism. Here we reported cDNA cloning, chromosome mapping,expression and
      evolutional analysis of sirtuin genes in Sus scrofa (Tongcheng pig). Sequence
      analysis showed that porcine sirtuin genes contain 7 members designated SIRT1-7.
      Tissue distribution analysis indicated porcine sirtuin genes ubiquitously
      expressed but with the highest abundance in brain, spinal cord and genital
      tissue. In silico and radiation hybrid mapping analysis mapped porcine SIRT1-7 to
      the chromosomes 14q23,6q11-12, 2q29, 14q19, 7p12, 2q11, and 12p15, respectively.
      We also isolated and characterized genomic sequence of porcine SIRT1, which
      spaned a region of 31,834 bp comprising 9 exons ranging in size from 80 bpto 2121
      bp. The 5' flanking genomic region preceding an open reading frame of SIRT1 has a
      TATA box, a small300 bp CpG island and several putative Sp1 and p53 transcription
      factor binding sites. Moreover, we isolated two novel splicing SIRT6 variants
      with 346 bp (variant 2) in-frame deletions from lung and 327 bp(variant 3) in
      frame deletions from spleen and brain. This is the first systematic report of
      molecular cloning and characterization of sirtuin genes in pigs, which will be
      helpful for a better understanding of the physiological role of sirtuin proteins
      in pigs.

PMID- 19389482
TI  - Neutralization of TNFalpha alters inflammation in guinea pig tuberculous
      pleuritis.
AB  - Previously, treatment with anti-gpTNFalpha antibody enhanced TNFalpha mRNA
      expression in pulmonary granulomas microdissected from non-vaccinated guinea
      pigs, and modified splenic granuloma architecture. In this study, pleural fluid,
      cells, and granulomatous tissues were collected 3, 5, and 8 days post-pleurisy
      induction in guinea pigs treated with anti-gpTNFalpha or normal serum control.
      Neutralizing TNFalpha reduced the percentage of macrophages in the pleural
      exudate while increasing the proportions of neutrophils and lymphocytes. Cell
      associated mycobacterial loads were increased in guinea pigs treated with anti
      gpTNFalpha antibody. Cells from the pleural exudate in both treatment groups at
      day 3 expressed predominantly TNFalpha and IFNgamma mRNA. By day 5, treatment
      with anti-gpTNFalpha antibody significantly reduced TNFalpha mRNA and increased
      TGFbeta and iNOS mRNA expression, a transition which did not occur in the control
      group until day 8. TNFalpha mRNA overwhelmed the cytokine milieu of
      microdissected pleural granulomas in the control group at day 3 whereas TNFalpha,
      IFNgamma, and TGFbeta mRNA dominated the anti-gpTNFalpha-treated group. At day 8,
      granulomas from the control group began shifting towards an anti-inflammatory
      profile with increased levels of TGFbeta mRNA. Neutralization of TNFalpha
      hastened the transition to an anti-inflammatory cytokine response in guinea pig
      pleural granulomas and exudate cells.

PMID- 19389483
TI  - OPA1 functions in mitochondria and dysfunctions in optic nerve.
AB  - OPA1 is the major gene responsible for Dominant Optic Atrophy (DOA), a blinding
      disease that affects specifically the retinal ganglion cells (RGCs), which
      function consists in connecting the neuro-retina to the brain. OPA1 encodes an
      intra-mitochondrial dynamin, involved in inner membrane structures and
      ubiquitously expressed, raising the critical question of the origin of the
      disease pathophysiology. Here, we review the fundamental knowledge on OPA1
      functions and regulations, highlighting their involvements in mitochondrial
      respiration, membrane dynamic and apoptosis. In light of these functions, we then
      describe the remarkable RGC mitochondrial network physiology and analyse data
      collected from animal models expressing OPA1 mutations. If, to date RGC
      mitochondria does not present any peculiarity at the molecular level, they
      represent possible targets of numerous assaults, like light, pressure, oxidative
      stress and energetic impairment, which jeopardize their function and survival, as
      observed in OPA1 mouse models. Although fascinating fields of investigation are
      still to be addressed on OPA1 functions and on DOA pathophysiology, we have
      reached a conspicuous state of knowledge with pertinent cell and animal models,
      from which therapeutic trials can be initiated and deeply evaluated.

PMID- 19389484
TI  - Transcriptional activity of the murine retinol-binding protein gene is regulated
      by a multiprotein complex containing HMGA1, p54 nrb/NonO, protein-associated
      splicing factor (PSF) and steroidogenic factor 1 (SF1)/liver receptor homologue 1
      (LRH-1).
AB  - Retinol-binding protein (RBP4) transports retinol in the circulation from hepatic
      stores to peripheral tissues. Since little is known regarding the regulation of
      this gene, we analysed the cis-regulatory sequences of the mouse RBP4 gene. Our
      data show that transcription of the gene is regulated through a bipartite
      promoter: a proximal region necessary for basal expression and a distal segment
      responsible for cAMP-induction. This latter region contains several binding sites
      for the structural HMGA1 proteins, which are important to promoter regulation. We
      further demonstrate that HMGA1s play a key role in basal and cAMP-induction of
      Rbp4 transcription and the RBP4 and HMGA1 genes are coordinately regulated in
      vitro and in vivo. HMGA1 acts to recruit transcription factors to the RBP4
      promoter and we specifically identified p54(nrb)/NonO and protein-associated
      splicing factor (PSF) as components that interact with this complex.
      Steroidogenic factor 1 (SF1) or the related liver receptor homologue 1 (LRH-1)
      are also associated with this complex upon cAMP-induction. Depletion of SF1/LRH-1
      by RNA interference resulted in a dramatic loss of cAMP-induction. Collectively,
      our results demonstrate that basal and cAMP-induced Rbp4 transcription is
      regulated by a multiprotein complex that is similar to ones that modulate
      expression of genes of steroid hormone biosynthesis. Since genes related to
      glucose metabolism are regulated in a similar fashion, this suggests that Rbp4
      expression may be regulated as part of a network of pathways relevant to the
      onset of type 2 diabetes.

PMID- 19389486
TI  - The transmembrane tyrosines Y56, Y91 and Y167 play important roles in determining
      the affinity and transport rate of the rabbit proton-coupled peptide transporter
      PepT1.
AB  - The mammalian proton-coupled peptide transporter PepT1 is widely accepted as the
      major route of uptake for dietary nitrogen, as well as being responsible for the
      oral absorption of a number of classes of drugs, including beta-lactam
      antibiotics and angiotensin-converting enzyme (ACE) inhibitors. Using site
      directed mutagenesis and zero-trans transport assays, we investigated the role of
      conserved tyrosines in the transmembrane domains (TMDs) of rabbit PepT1 as
      predicted by hydropathy plots. All the individual TMD tyrosines were substituted
      with phenylalanine and shown to retain the ability to traffic to the plasma
      membrane of Xenopus laevis oocytes. These single substitutions of TMD tyrosines
      by phenylalanine residues did not affect the proton dependence of peptide uptake,
      with all retaining wild-type PepT1-like pH dependence. Individual mutations of
      four of the nine TMD residue tyrosines (Y64, Y287, Y345 and Y587) were without
      measurable effect on PepT1 function, whereas the other five (Y12, Y56, Y91, Y167
      and Y345) were shown to result in altered transport function compared to the wild
      type PepT1. Intriguingly, the affinity of Y56F-PepT1 was found to be dramatically
      increased (approximately 100-fold) in comparison to that of the wild-type rabbit
      PepT1. Y91 mutations also affected the substrate affinity of the transporter,
      which increased in line with the hydrophilicity of the substituted amino acid
      (F>Y>Q>R). Y167 was demonstrated to play a pivotal role in rabbit PepT1 function
      since Y167F, Y167R and Y167Q demonstrated very little transport function. These
      results are discussed with regard to a proposed mechanism for PepT1 substrate
      binding.

PMID- 19389487
TI  - OPA1-associated disorders: phenotypes and pathophysiology.
AB  - The OPA1 gene, encoding a dynamin-like mitochondrial GTPase, is involved in
      autosomal dominant optic atrophy (ADOA, OMIM #165500). ADOA, also known as Kjer's
      optic atrophy, affects retinal ganglion cells and the axons forming the optic
      nerve, leading to progressive visual loss. OPA1 gene sequencing in patients with
      hereditary optic neuropathies indicates that the clinical spectrum of ADOA is
      larger than previously thought. Specific OPA1 mutations are responsible for
      several distinct clinical presentations, such as ADOA with deafness (ADOAD), and
      severe multi-systemic syndromes, the so-called "ADOA plus" disorders, which
      involve neurological and neuromuscular symptoms similar to those due to
      mitochondrial oxidative phosphorylation defects or mitochondrial DNA instability.
      The study of the various clinical presentations of ADOA in conjunction with the
      investigation of OPA1 mutations in fibroblasts from patients with optic atrophy
      provides new insights into the pathophysiological mechanisms of the disease while
      underscoring the multiple physiological roles played by OPA1 in energetic
      metabolism, mitochondrial structure and maintenance, and cell death. Finally,
      OPA1 represents an important new paradigm for emerging neurodegenerative diseases
      affecting mitochondrial structure, plasticity and functions.

PMID- 19389485
TI  - Structural and functional link between the mitochondrial network and the
      endoplasmic reticulum.
AB  - Mitochondrial and endoplasmic reticulum (ER) networks are fundamental for the
      maintenance of cellular homeostasis and for determination of cell fate under
      stress conditions. Recent structural and functional studies revealed the
      interaction of these networks. These zones of close contact between ER and
      mitochondria called MAM (mitochondria associated membranes) support communication
      between the two organelles including bioenergetics and cell survival. The
      existence of macromolecular complexes in these contact sites has also been
      revealed. In this contribution, we will review: (i) the ER and mitochondria
      structure and their dynamics, (ii) the basic principles of ER mitochondrial
      Ca(2+) transport, (iii) the physiological/pathological role of this cross-talk.

PMID- 19389488
TI  - Pathogenic mutations in the 5' untranslated region of BCS1L mRNA in mitochondrial
      complex III deficiency.
AB  - Mutations in the assembly chaperone BCS1L constitute a major cause of
      mitochondrial complex III deficiency. We studied the presence of BCS1L mutations
      in a complex III-deficient patient with metabolic acidosis, liver failure, and
      tubulopathy. A previously reported mutation, p.R56X, was identified in one BCS1L
      allele, and two novel heterozygous mutations, g.1181A>G and g.1164C>G, were
      detected in the second allele. The g.1181A>G mutation generated an alternative
      splicing site in the BCS1L transcript, causing a 19-nucleotides deletion in its
      5'UTR region. Decreased BCS1L mRNA and protein levels, and a respiratory chain
      complex III assembly impairment, determine a pathogenic role for the novel BCS1L
      mutations.

PMID- 19389489
TI  - Endothelial dysfunction--an obstacle of therapeutic angiogenesis.
AB  - Due to ageing populations and improvements in survival, increasing numbers of
      patients suffering from ischemic cardiovascular disease are not amenable to
      revascularization. Hence, interests are currently focused on "therapeutic
      angiogenesis", which is the clinical use of growth factors to enhance or promote
      the development of collateral blood vessels in ischemic tissue. Several growth
      factors (or genes encoding these growth factors) are now available for
      therapeutic vascular growth in normal and ischemic tissues. However, the
      successes of angiogenic therapy observed in pre-clinical studies have not been
      realized in clinical trials. Most animal studies demonstrating the physiologic
      effectiveness of angiogenic therapies have been performed in normal young
      animals, while clinical trials typically enroll older patients with various
      endothelial disruptive risk factors. The promising results of trials using
      endothelial function-improving strategies support the hypothesis that the
      decreased effectiveness of growth factor therapy due to endothelial dysfunction
      could be a principle reason for failure of trials using growth factors. We will
      have a retrospection of therapeutic angiogenesis trials and discuss the
      mechanisms that contribute to an impaired angiogenic response in the setting of
      endothelial dysfunction. We also briefly explore endothelial function-improving
      procedures that have the potentially therapeutic benefit of enhancing the
      angiogenic response.

PMID- 19389490
TI  - Anti-aquaporin-4 auto-antibodies orchestrate the pathogenesis in neuromyelitis
      optica.
AB  - NMO-IgG, the auto-antibody specific to the aquaporin-4 (AQP4) water channel
      associated with the autoimmune inflammatory disease neuromyelitis optica (NMO),
      is considered to be an accurate serum biomarker and is thought to be an important
      contributor to NMO pathology. In this review, we summarize recent evidences from
      our group and others indicating that NMO-IgG can be implicated at several levels
      in the immuno-pathology of NMO. NMO-IgG/anti-AQP4 antibodies may compromise the
      integrity of the blood-brain barrier and consequently facilitate and enhance the
      perivascular inflammation characteristic of NMO. Lastly, NMO-IgG can induce
      astrocyte injury which may lead to the accumulation of excitatory/toxic molecules
      and accordingly damage oligodendrocytes and compromise myelin integrity.

PMID- 19389491
TI  - Acute transverse myelitis: a practical reappraisal.
AB  - Acute transverse myelitis (ATM), a subgroup of various conditions that cause
      transverse spinal cord syndromes, is an inflammatory and usually idiopathic
      spinal cord disease. Idiopathic ATM is diagnosed according to established
      criteria which mainly assure a clinical picture of bilateral symptoms and signs
      attributable to spinal cord disease, existence of focal cord inflammation by
      magnetic resonance imaging and cerebrospinal fluid studies, and exclusion of many
      diseases, especially cord compression and "disease-associated ATM", as Sjogren
      disease. Patients with idiopathic ATM have motor, sensory and autonomic
      dysfunctions with acute or subacute onset, progressing to nadir in 4 h to 21
      days, with full or partial recovery in most cases. Emergent treatment to halt
      inflammation with corticosteroids is required as well as early appropriate
      symptomatic therapies. Recent discovery of novel biomarkers has set apart
      specific inflammatory and autoimmune myelopathies, namely paraneoplastic myelitis
      and neuromyelitis optica spectrum diseases, the diagnosis of which is crucial to
      establish therapeutic strategies.

PMID- 19389492
TI  - Medico-legal consequences of post-operative intra-abdominal adhesions.
AB  - Post-operative adhesions are an almost invariable consequence of abdominal or
      pelvic surgery, no matter whether this is performed by the open or laparoscopic
      technique. Their most important morbidity is small bowel obstruction, but other
      sequelae include female infertility and dyspareunia, and increased risk of
      visceral injury at any subsequent laparotomy or laparoscopy. Whether chronic
      abdominal pain is truly a consequence of adhesions is still a matter of some
      discussion, but it is likely to be accepted as an entity both by patients and by
      their legal advisors. While there is currently a scarcity of published literature
      on the subject, a recent assessment of adhesion-related medico-legal claims dealt
      with by the British medical defence associations has been undertaken. Successful
      medico-legal claims include cases of bowel perforation after laparoscopic
      division of adhesions, delays in the diagnosis of adhesion obstruction of the
      small bowel, infertility as a result of adhesions and 'pain'. This problem is
      unlikely to be unique to the UK alone and general practitioners, surgeons and
      gynaecologists worldwide need to be aware of the increasing burden of medico
      legal claims arising from the complications of intra-abdominal adhesions. Most
      importantly they need to consider whether it is now timely to take steps to avoid
      them.

PMID- 19389493
TI  - Multiple myeloma in the era of novel agents.

PMID- 19389494
TI  - Staging systems and prognostic factors as a guide to therapeutic decisions in
      multiple myeloma.
AB  - Multiple myeloma (MM) patients have a highly variable disease course and survival
      varies from a few months to more than 10 years. Numerous prognostic factors have
      been identified, including age, performance status (PS), serum albumin, beta2
      microglobulin (beta2M), lactate dehydrogenase (LDH), renal function, genetic
      factors, and serum free light chains (sFLCs) or their ratio (sFLCR). Several
      models have been built to separate patients into various risk groups with
      different outcomes. Staging systems need to be simple, accurate, and readily
      available in order to effectively guide treatment decisions now that effective
      treatments exist that prolong survival. The International Staging System (ISS) is
      currently in use; it is highly prognostic but presents some limitations. We
      suggest that the ISS prognostic potential could be improved with the addition of
      sFLCR and eventually LDH.

PMID- 19389495
TI  - Front-line treatment in younger patients with multiple myeloma.
AB  - The treatment of newly diagnosed myeloma has evolved rapidly. The choice of
      initial therapy depends on eligibility for stem cell transplantation, as well as
      baseline risk factors. Eligibility for transplantation is important since the
      choice of initial therapy is primarily melphalan-based in patients who are not
      candidates for transplant, while melphalan-containing regimens are avoided as
      induction therapy in transplant candidates. An assessment of risk based on
      independent prognostic markers is important mainly for prognosis but may have
      some value in choice of initial therapy. For example, bortezomib-based regimens
      may have particular value in patients with certain high-risk features. This
      review discusses the current status of front-line therapy in younger patients
      with myeloma who are candidates for stem cell transplantation.

PMID- 19389496
TI  - The role of high-dose therapy with autologous stem cell support in the era of
      novel agents.
AB  - This review discusses the initial studies concerning the role of high-dose
      therapy (HDT) in multiple myeloma (MM) and gives the major conclusions drawn from
      this "historical period." Later, current studies using new drugs for HDT
      (induction, conditioning regimen, consolidation, and maintenance) are described
      and the promising results of this strategy reported. Finally, the issue of HDT in
      the era of new drug regimens is discussed, as well as the necessity of designing
      future trials comparing HDT and new drug regimens.

PMID- 19389497
TI  - Frontline treatment in elderly patients with multiple myeloma.
AB  - Melphalan-prednisone-thalidomide (MPT) and melphalan-prednisone-bortezomib (MPV)
      currently appear to be the treatments of choice for a large proportion of elderly
      multiple myeloma (MM) patients ineligible for autologous stem cell
      transplantation (ASCT). It seems certain that in the near future cyclophosphamide
      thalidomide-dexamethasone, with an attenuated dose of dexamethasone (CTDa), and
      melphalan-prednisone-lenalidomide (MPR) will also be proved superior to MP, thus
      providing four therapeutic options in this patient group. These options could
      lead to more personalized treatment approaches, based on patient comorbidities,
      as the three novel agents have somewhat different toxicity profiles. MP would be
      appropriate for only a minority of patients with poor performance status and/or
      significant comorbidities. Questions regarding the relative efficacy of different
      melphalan-based regimens or melphalan-based regimens versus dexamethasone-based
      regimens with low-dose dexamethasone will require further trials. Additionally,
      the important issue of maintenance treatment needs to be investigated. These new
      and emerging therapies provide multiple effective treatment options for MM
      patients and greatly enhanced treatment strategies for clinicians, all offering
      promise that has been sorely lacking over the past four decades.

PMID- 19389498
TI  - Treatment of relapsed/refractory multiple myeloma.
AB  - The introduction of several novel and active treatments and improvements in
      supportive care of myeloma patients has resulted in a prolongation of the
      survival of these patients. However, myeloma remains an incurable disease and
      almost all patients will relapse. Effective management of the
      relapsing/refractory disease incorporates several different strategies, depending
      on prior treatments, responses, and duration of responses, as well as residual
      toxicity, age, and physical condition. High-dose dexamethasone still has a role
      in the management of disease complications such as cytopenias, renal impairment,
      or spinal cord compression until another agent is added. High-dose therapy may be
      considered for selected patients who have a long-term treatment-free interval
      after their first transplantation. Allogeneic transplantation is limited to
      selected young patients, preferably with an HLA-matched donor. However, the
      backbone of current strategies for the management of relapsed/refractory myeloma
      includes the novel agents thalidomide, bortezomib, and lenalidomide. These
      agents, either with dexamethasone or in combination with chemotherapy, have shown
      significant activity both in relapsed and in refractory patients. Based on the
      results of phase III trials, lenalidomide and bortezomib have increased the post
      relapse survival and are active in patients who have received prior novel agents;
      lenalidomide is active in thalidomide-pretreated or bortezomib-pretreated
      patients and bortezomib alone or in combination with chemotherapy is active in
      thalidomide/lenalidomide-pretreated patients. Combinations of novel agents show
      synergistic activity and may overcome drug resistance. Finally, special
      consideration is needed for the management of patients with renal impairment or
      other poor prognostic features.

PMID- 19389499
TI  - Role of allogeneic stem cell transplantation in multiple myeloma.
AB  - High-dose chemotherapy with autologous stem cell rescue has been regarded as the
      standard of care for young newly diagnosed myeloma patients. Moreover, the
      development of new agents with potent anti-tumor activity has further improved
      survival. However, relapse is a continuous risk primarily due to the inability of
      current therapies to eradicate all myeloma cells. Allografting is the only
      potentially curative treatment at least for a subset of multiple myeloma patients
      due to its well documented graft-versus-myeloma effects. Given the high
      transplant mortality of the high-dose myeloablative conditionings used until
      recently, allografting has for a long time been limited to younger
      relapsed/refractory patients. These limitations have been reduced significantly
      by the use of reduced-intensity conditionings. Although results of recent trials
      are encouraging, the subset of patients who may benefit most from an allograft
      remains to be determined. An overview of the clinical outcomes obtained with
      allografting and possible future developments are reported.

PMID- 19389501
TI  - Management of complications in multiple myeloma.
AB  - Multiple myeloma (MM) is characterized by the presence of osteolytic bone
      disease, renal impairment, anemia, and immune dysfunction. Adequate supportive
      care is considered an essential part of anti-myeloma therapy. The administration
      of bisphosphonates has been shown to reduce skeletal related events and
      hypercalcemia. Bisphosphonates are well tolerated, but preventive steps should be
      taken to avoid renal impairment and osteonecrosis of the jaw (ONJ). Adequate pain
      control is of crucial importance for the quality of life of MM patients. Local
      radiotherapy may rapidly ameliorate symptoms of painful MM bone lesions, and
      vertebroplasty and kyphoplasty are able to control symptoms and restore the
      original height of vertebral fractures. Symptomatic chemotherapy-induced anemia
      should preferentially be treated with erythropoietic growth factors, but further
      studies are required to confirm the long-term safety of this approach. Light
      chain-induced renal impairment should be treated without delay with a highly
      effective anti-myeloma regimen consisting of novel drugs. Prophylaxis of
      infections should be considered particularly in patients with poorly controlled
      disease and documented infections should be treated aggressively as they
      contribute significantly to morbidity and mortality. The concerted action of
      these supportive therapies can significantly improve the quality of life of MM
      patients during the different phases of their disease.

PMID- 19389500
TI  - Emerging treatments for multiple myeloma: beyond immunomodulatory drugs and
      bortezomib.
AB  - The successful clinical development of thalidomide, bortezomib, and lenalidomide
      not only transformed the therapeutic management of multiple myeloma (MM) but also
      catalyzed a renewed interest in the development of additional classes of novel
      agents for this disease. This review focuses on a series of new therapeutics that
      have shown promising preclinical results, as well as encouraging safety profiles
      and early evidence of anti-MM activity in clinical studies, either alone or in
      combination with other, conventional or novel, anti-MM treatments. These agents
      include second-generation proteasome inhibitors and immunomodulatory agents, as
      well as members of other therapeutic classes, such as histone deacetylase
      inhibitors (HDAC), heat shock protein 90 (Hsp90) inhibitors, and the
      alkylphospholipid Akt inhibitor perifosine.

PMID- 19389502
TI  - Imatinib mesylate efficacy in 72 previously treated Philadelphia-positive chronic
      myeloid leukemia patients with and without additional chromosomal changes: single
      center results.
AB  - Reported here are 72 previously treated Philadelphia chromosome-positive (Ph+)
      CML patients on imatinib (IM) therapy, with a focus on patients with additional
      chromosomal aberrations (CAs). At the start of IM treatment, 49 patients
      exhibited only the Ph chromosome (68%) and 23 patients (32%) had one or more
      additional CAs. The most frequent additional changes were deletions on the
      der(9q) (8 of 23), trisomy 8 (3 of 23), and an extra copy of the Ph chromosome (2
      of 23). Five patients had a complex karyotype. At the latest follow-up, 49 of the
      72 patients (68%) were alive, including 15 of the 23 patients with additional CAs
      (65%). Median follow-up was 6.6 years; median duration of IM treatment was 4.4
      years. In all, 35 of the 49 patients with Ph only (71%) and 10 of the 23 patients
      with additional CAs (43%) achieved complete cytogenetic response. All patients
      with deletion on der(9q) achieved complete cytogenetic response. There was no
      statistically significant difference in the overall survival of patients with
      additional CAs and patients with Ph as the sole abnormality. Patients in
      accelerated phase had significantly worse overall survival on IM, regardless of
      additional CAs. The present results confirm that the majority of previously
      treated Ph+ CML patients benefit from starting IM therapy, including patients
      with defined additional changes. In contrast, patients with complex karyotypes
      have poor prognosis, even with IM.

PMID- 19389503
TI  - Genomic amplification of the human telomerase RNA gene for differential diagnosis
      of cervical disorders.
AB  - To evaluate genomic amplification of the human telomerase RNA gene (TERC) as a
      supportive approach to cytopathology or histopathology in diagnosis of low-grade
      and high-grade uterine cervical lesions, 1,033 Chinese women at three medical
      centers had liquid-based thin-layer cytopathologic examination and TERC detection
      by fluorescence in situ hybridization (FISH). Human papillomavirus DNA testing,
      colposcopy with or without biopsy, and histopathologic examination were conducted
      as needed. In cytopathologic examination, genomic amplification of TERC was found
      in 30 of 659 (4.6%) normal or benign cellular changes; in 23 of 170 (13.5%)
      atypical squamous cells of undetermined significance (ASCUS); in 8 of 28 (28.6%)
      atypical squamous cells with high-grade squamous intraepithelial lesion possible
      (ASC-H); and in 26 of 103 (25.2%) low-grade (LSIL) and 64 of 73 (87.7%) high
      grade (HSIL) squamous intraepithelial lesions; with pairwise significant
      difference (P< 0.05) in each, except ASC-H and LSIL (chi(2) = 0.127, P = 0.72).
      In histopathologic examination, TERC was amplified in 28 of 671 (4.2%) normal,
      inflammatory, or wart cases; in 17 of 233 (7.3%) cervical intraepithelial
      neoplasia grade 1 cases (CIN 1); in 27 of 39 (69.2%) CIN 2 cases; in 57 of 67
      (85.1%) CIN 3 cases; and in 22 of 23 (95.7%) cervical cancer cases; with pairwise
      significant difference in each (P < 0.05). The number of cells with abnormal
      signals increased and the abnormal signal patterns were diversified with
      increasing severity of cervical dysplasia. FISH detection of TERC amplification
      may provide an effective, noninvasive approach in conjunction with cytopathologic
      or histopathologic evaluation for differential diagnosis of low- and high-grade
      cervical disorders.

PMID- 19389505
TI  - High-resolution genomic profiling of pediatric lymphoblastic lymphomas reveals
      subtle differences with pediatric acute lymphoblastic leukemias in the B-lineage.
AB  - Lymphoblastic lymphoma (LBL) is one of the most frequent occurring pediatric non
      Hodgkin lymphomas. In the WHO classification scheme, pediatric LBL is considered
      to be the same disease entity as pediatric acute lymphoblastic leukemia (ALL).
      However, it is unclear whether the genetic basis of pediatric LBL development is
      similar to that of pediatric ALL. We performed genome-wide analyses of copy
      number aberrations in 12 T-LBL and 7 precursor B-cell LBL pediatric cases using
      high-resolution SNP-based array CGH. Similar to what previously has been found in
      T-ALL, T-LBL exhibited recurrent deletions of the CDKN2A locus, occurring in 92%
      of the cases. Additionally, we detected deletions of RB1 (16%), duplications of
      MYB (16%), and an amplification of ABL1 in one case. These results show that,
      similar to T-ALL, the genomic alterations in T-LBL predominantly target genes
      involved in cell cycle progression. The majority of precursor B-cell LBL was
      characterized by high-hyperdiploidy (71%), and showed high resemblance with high
      hyperdiploid precursor B-cell ALL. Taken together, our data suggest that
      pediatric LBL and ALL exhibit similar genomic abnormalities within confined
      immunophenotypic and cytogenetic subgroups, but that the representations of these
      subgroups differs between the two entities.

PMID- 19389504
TI  - Recurrent and nonrandom DNA copy number and chromosome alterations in Myc
      transgenic mouse model for hepatocellular carcinogenesis: implications for human
      disease.
AB  - Mouse models for hepatocellular carcinoma (HCC) provide an experimental ground
      for dissecting the genetic and biological complexities of human liver cancer and
      contribute to our ability to gain insights into the relevance of candidate cancer
      genes. We examined, using spectral karyotyping (SKY) and array-based CGH (aCGH),
      seven cell lines derived from HCC spontaneously developed in transgenic Myc mice
      (Myc), and four cell lines established from tumors induced in nude mice by
      inoculation with the original Myc cells (nuMyc). All the cell lines exhibited
      gain of material from chromosomes 5, 6, 8, 10, 11, 15, and 19 and DNA copy-number
      loss from chromosomes 2, 4, 7, 9, 12, 14, and X. In addition, several recurrent
      chromosome reorganizations were found, including del(3), t(3;8), del(4), t(4;11),
      t(6;5), del(7), del(8), del(9), t(10;14), del(11), and del(16). Chromosome
      breakpoints underlying rearrangements clustered in the regions previously
      identified as important for the early stages of Myc-induced hepatocarcinogenesis.
      The results strongly suggest the importance of recurrent breakage and loss of
      chromosomes 4, 9, and 14 and gain of chromosomes 15 and 19 in mouse liver
      neoplasia. Genomic changes observed in Myc HCC cell lines are also recurrent in
      HCC developed in other transgenic mouse models, in mouse spontaneous HCC and
      derivative cell lines, and in preneoplastic liver lesions induced with chemical
      carcinogens. Overall, the present results document selective, nonrandom genomic
      changes involving chromosomal regions homologous to those implicated in human
      HCC.

PMID- 19389506
TI  - AKT1 E17 K pleckstrin homology domain mutation in urothelial carcinoma.
AB  - The PI3K/AKT pathway is frequently activated in human cancer. Recently, a G to A
      point mutation (E17K) was found in the pleckstrin homology domain of AKT1. We
      aimed to explore this mutation in cases of urothelial carcinoma. Using chip-based
      matrix-assisted laser desorption-time-of-flight (MALDI-TOF) mass spectrometer,
      AKT1 E17K mutation was searched in 26 total RNA samples obtained from 26 patients
      known to have urothelial carcinoma. Mutation was found in one out of 26 (3.8%)
      patients - a 46 year old female with a low grade transitional cell carcinoma
      located to the lamina propria (Ta disease). Our finding is in line with previous
      studies showing AKT1 E17K mutation to be rare. Yet, further studies are required
      to determine whether this mutation is indeed related to less aggressive disease
      and carries better prognosis.

PMID- 19389507
TI  - Intercellular centrosome number is correlated with the copy number of chromosomes
      in bladder cancer.
AB  - Centrosome amplification, which may accelerate tumor progression through
      chromosomal instability, is frequently observed in human malignancies. The
      intercellular relation between the number of centrosomes and chromosomes,
      however, is poorly understood. Therefore, the relationship between centrosomes
      and chromosomal copy number in the same cells was investigated in bladder cancer.
      Centrosomes were evaluated by immunohistochemistry, using anti-gamma-tubulin
      antibody in eight bladder cancer cell lines. Fluorescence in situ hybridization
      with centromeric probes for chromosomes 7, 9, and 17 was then performed on the
      same cells stained with gamma-tubulin. The number of centrosomes was directly
      proportional to the number of chromosomes in cells with centrosome amplification,
      while a large intercellular variation in chromosomal copy number was detected in
      cells with normal numbers of centrosomes. Cancer cells with centrosome
      amplification of even centrosome numbers had significantly more even numbers of
      chromosomes. In cancer cells with four centrosomes, even numbers of chromosomes
      were detected more frequently (87.5%). These bladder cancer cell lines showed
      Aurora-A and p53 overexpression. These data indicate the occurrence of centrosome
      amplification with the possible mechanism of cytokinesis failure, resulting in a
      doubling of the number of centrosomes and chromosomes.

PMID- 19389508
TI  - Translocation (2;8)(q35;q13): a recurrent abnormality in congenital embryonal
      rhabdomyosarcoma.
AB  - We report a case of congenital embryonal rhabdomyosarcoma (ERMS), a rare form of
      rhabdomyosarcoma, featuring a karyotype with a t(2;8)(q35;q13) in a 2-week-old
      male infant. This is the third reported case of congenital ERMS with cytogenetic
      findings. The previous cases also showed a similar or possibly identical
      translocation. We postulate that the t(2;8)(q35;q13) is a specific abnormality in
      congenital ERMS, and that it involves the PAX3 gene at 2q35 and a non-yet
      identified gene at 8q13.

PMID- 19389509
TI  - Malignant granular cell tumor of the ulnar nerve with novel cytogenetic and
      molecular genetic findings.
AB  - We report an unusual case of ulnar nerve-based malignant granular cell tumor
      characterized by gains of chromosome 10 and loss of P16 detected by conventional
      karyotyping and by fluorescence in situ hybridization, respectively, in a 74-year
      old male. To our knowledge, these findings have never been reported previously in
      malignant granular cell tumors.

PMID- 19389510
TI  - Therapy-related acute lymphoblastic leukemia with t(9;22)(q34;q11.2):a case study
      and review of the literature.
AB  - Therapy-related acute lymphoblastic leukemia (t-ALL) with t(9;22)(q34;q11.2) is
      rarely reported as a secondary malignant neoplasm. To our knowledge, only 10 Ph+
      t-ALL cases have been reported in the literature. However, 8/10 cases were not
      reported individually but constituted parts of larger studies reporting
      cytogenetic abnormalities in secondary leukemia. Snyder et al. first reported Ph+
      t-ALL in two patients who had been treated successfully for Ewing sarcoma. We
      present a novel case of t-ALL with t(9;22) in a patient with primary breast
      cancer. The interval between diagnosis of breast cancer and the appearance of ALL
      was 4 years. The patient was treated with partial mastectomy and axillary lymph
      node dissection followed by six cycles of CMF (cyclophosphamide, methotrexate, 5
      fluorouracil) chemotherapy and radiation therapy. Bone metastases were found 3
      years after surgery, and she was treated with epirubicin and paclitaxel. This
      case has the following unique features: BCR/ABL gene rearrangement in t-ALL, and
      two types of malignant cells (leukemic lymphoblasts and metastatic breast cancer
      cells) coexisted in the bone marrow.

PMID- 19389511
TI  - Three-way Philadelphia variant t(9;22;14)(q34;q11.2;p11) in chronic myeloid
      leukemia.

PMID- 19389512
TI  - Cytogenetic abnormality involving 8p11.2 in T-lymphoblastic lymphoma: report of a
      new case.

PMID- 19389513
TI  - Translocation (1;3)(p36;q21) at relapse in a child with acute myeloid leukemia
      and normal karyotype at diagnosis.

PMID- 19389514
TI  - Secondary structure and 3D homology modeling of swine leukocyte antigen class 2
      (SLA-2) molecules.
AB  - No information to date is available to elucidate the structure of swine leukocyte
      antigen class I (SLA-I) molecule which is comprised by a heavy chain of SLA-I non
      covalently associated with a light chain, beta(2)-microglobulin (beta(2)m)
      proteins. Presently, one of SLA-I gene SLA-2 and beta(2)m gene were expressed as
      soluble maltose binding proteins (MBP-proteins) in a pMAL-p2X/Escherichia coli
      TB1 system and identified by western blotting with anti-MBP polyclonal
      antibodies. The expressed proteins MBP-SLA-2 and MBP-beta(2)m were purified on
      amylose affinity columns followed by DEAE-Sepharose. The purified products were
      cleaved by Factor Xa, respectively, and the interest of proteins SLA-2 and
      beta(2)m were purified on amylose affinity columns followed by separation from
      MBP on DEAE-Sepharose. The secondary structures of SLA-2 and beta(2)m were
      analyzed by circular dichroism (CD) spectrophotometry. The three-dimensional (3D)
      structure of their peptide-binding domain (PBD) was modeled-based sequence
      homology. The content of the alpha-helix, beta-sheet, turn, and random coil in
      the SLA-2 protein were 76, 95, 36, and 67aa, respectively. In the 98aa of
      beta(2)m, the contents of the alpha-helix, beta-sheet, turn, and random coil were
      0, 45, 8, and 45aa, respectively. The SLA-2 protein displayed a typical alpha
      helix structure while beta(2)m protein displayed a typical beta-sheet structure.
      Homology modeling of the SLA-2 and beta(2)m proteins demonstrated similarities
      with the structure of human and mouse MHC (major histocompatibility complex)
      class I proteins.

PMID- 19389515
TI  - Antitumor efficacy induced by human ovarian cancer cells secreting IL-21 alone or
      combination with GM-CSF cytokines in nude mice model.
AB  - The ovarian cancer cells (SKOV3) secreting IL-21 alone or combination with GM-CSF
      cytokines was developed and its antitumor effect was evaluated in the nude mice.
      The gene of IL-21 was amplified from plasmid pRSC-IL-21 by PCR, cloned into the
      plasmid pRSC-GM-CSF, and the plasmid pRSC-GM-CSF-IL21 was constructed. The
      plasmids of pRSC-GM-CSF, pRSC-IL21, pRSC-GM-CSF-IL21 and pRSC were respectively
      transfected into the SKOV3 cells and antitumor efficacy induced by the SKOV3
      cells secreting IL-21 or combination with GM-CSF was evaluated by surveying the
      tumor growth and the nude mice's survival. The results indicated that the
      secreted IL-21 and GM-CSF were functional because the culture supernatant of
      SKOV3 cells transfected with the plasmid pRSC-GM-CSF-IL21 enhanced NK
      cytotoxicity in vitro. The expressions of MIC A/B, NKG2D and ICAM-1 molecules on
      the SKOV3 cells were up-regulated. The level of IFN-gamma and TNF-alpha, the NK
      cytotoxicity and the antitumor efficacy were significantly increased in the null
      mice inoculated with the SKOV3 cells secreting both IL-21 and GM-CSF in
      comparison with the nude mice inoculated with the other different SKOV3 cells. We
      concluded that the SKOV3 cells genetically engineered to secrete biologically
      active IL-21 and GM-CSF elicited antitumor immunity effectively through enhancing
      NK cytotoxicity, promoting the expressions of MIC A/B , ICAM-1 and NKG2D
      molecules as well as elevating level of IFN-gamma and TNF-alpha in the nude mice
      model.

PMID- 19389516
TI  - Anti-tumor necrosis factor therapy and interpreting tuberculin skin tests.

PMID- 19389518
TI  - Maspin expression, angiogenesis, prognostic parameters, and outcome in malignant
      melanoma.
AB  - BACKGROUND: Maspin is a serine protease inhibitor that is thought of as a tumor
      suppressor because of observations that loss of maspin expression in breast,
      prostate, and oral cancer is associated with poor prognosis. In addition, maspin
      may function as an inhibitor of angiogenesis. However, it has been correlated
      with malignant behavior in pancreatic and ovarian cancer. The role of maspin in
      malignant melanoma (MM) has not yet been systematically examined. OBJECTIVE: We
      aimed to examine the immunohistochemical expression of maspin and several
      proangiogenic factors (vascular endothelial growth factor, transforming growth
      factor-beta, alphaVbeta3 integrin, cyclooxygenase-2, and CD44) in MM and
      correlate each to angiogenesis, tumor thickness, and outcome. METHODS: In all, 77
      formalin-fixed, paraffin-embedded MM samples were immunostained for maspin and
      other proangiogenic factors (vascular endothelial growth factor, transforming
      growth factor-beta, alphaVbeta3 integrin, cyclooxygenase-2, and CD44) and were
      correlated with angiogenesis as mean microvessel density. Three normal-appearing
      skin samples and 10 nevi were also immunostained for maspin. Breslow thickness,
      Clark level, clinical stage, and follow-up information were obtained for outcome
      analysis. RESULTS: Immunohistochemical analysis revealed strong nuclear
      melanocytic maspin expression in all 10 nevi (half of which were dysplastic) but
      none in melanocytes from 3 normal-appearing skin samples. Strong nuclear maspin
      staining was demonstrated in 78% of radial phase melanoma and 46% of vertical
      growth phase melanoma. In addition, there was a significant inverse relationship
      between maspin and microvessel density (P = .018) and tumor thickness greater
      than 0.76 mm (P = .007), indicating that maspin is expressed in thinner tumors
      with less angiogenesis. Conversely, vascular endothelial growth factor
      expression, Clark level, and Breslow thickness all significantly correlated with
      microvessel density (P = .047, P = .027, and P = .011, respectively).
      Cyclooxygenase-2 expression significantly correlated with thicker tumors (P =
      .006) but not with angiogenesis (P = .714). In addition, Clark level, Breslow
      thickness, and stage were all significant predictors of overall survival (P <
      .001, P = .005, and P < .001, respectively). LIMITATIONS: This study represents a
      single institution. CONCLUSION: These results demonstrate maspin expression in
      nevi and radial growth phase melanoma, but this expression seems to be lost in
      the transition from radial growth phase to vertical growth phase melanoma. In
      addition, maspin is correlated with decreased angiogenesis and tumor thickness
      less than 0.76 mm in MM. These results indicate maspin may function as a tumor
      suppressor in MM.

PMID- 19389519
TI  - The prevalence of melanocytic nevi on the soles in the Japanese population.
AB  - BACKGROUND: Acral lentiginous melanoma (ALM) is the most common type of melanoma
      in Japan. The association between ALM and acral nevus has not been elucidated.
      OBJECTIVE: To investigate the prevalence and dermatoscopic patterns of plantar
      melanocytic nevi on the soles in the Japanese and to evaluate the relationship
      between acral nevi and ALM. METHODS: All outpatients (N = 1697) and melanoma
      patients (N = 104) were included. We examined the number, size, and dermatoscopic
      images of nevi. RESULTS: In the control group, the prevalence of plantar nevi was
      10.9%, and the mean size was 3.8 +/- 2.4 mm. The prevalence of nevi in patients
      with ALM and melanoma in situ on the soles was 8.6% and that of patients with
      melanoma on other sites was 14.5%. The main dermatoscopic pattern was "parallel
      furrow" in both groups. LIMITATIONS: This was a clinical observational study
      only. CONCLUSION: The number, size, and dermatoscopic patterns of nevi on the
      soles of patients with ALM and melanoma in situ on the soles did not differ from
      those of the control group.

PMID- 19389517
TI  - Strategies for early melanoma detection: Approaches to the patient with nevi.
AB  - Given its propensity to metastasize and the lack of effective therapies for most
      patients with advanced disease, early detection of melanoma is a clinical
      imperative. Although there are no noninvasive techniques for the definitive
      diagnosis of melanoma, and the "gold standard" remains biopsy with histologic
      examination, a variety of modalities may facilitate early melanoma diagnosis and
      the detection of new and changing nevi. This article reviews the general clinical
      principles of early melanoma detection and various modalities that are currently
      available or on the horizon, providing the clinician with an up to date
      understanding of management strategies for their patients with numerous or
      atypical nevi. LEARNING OBJECTIVE: After completing this learning activity,
      participants should understand the clinical importance of early melanoma
      detection, appreciate the challenges of early melanoma diagnosis and which
      patients are at highest risk, know the general principles of early melanoma
      detection, be familiar with current and emerging modalities that may facilitate
      early melanoma diagnosis and the detection of new and changing nevi, know the
      advantages and limitations of each modality, and be able to practice a combined
      approach to the patient with numerous or clinically atypical nevi.

PMID- 19389520
TI  - Unusual cutaneous manifestations of B-cell chronic lymphocytic leukemia.
AB  - BACKGROUND: B-cell chronic lymphocytic leukemia (B-CLL) is a low-grade
      lymphoproliferative disorder with characteristic histomorphologic features and an
      identifiable immunophenotype. The skin can be involved in the context of known
      disease, but cutaneous signs are rarely the presenting findings. OBJECTIVE:
      Evaluation of unusual clinical cutaneous presentations of B-CLL. METHODS: We
      conducted a retrospective case series analysis of 3 patients with unusual
      cutaneous clinicopathologic presentations of B-cell chronic lymphocytic leukemia,
      including erythematous plaques, angiomatosis/telangiectasia, and erosive skin
      changes, respectively, without a previous clinical history of chronic lymphocytic
      lymphoma. Main outcome measures were clinical cutaneous presentations and
      histopathologic results in the diagnosis of underlying disease. RESULTS: In the 3
      cases, lesion locations were the lower cheek, lower extremity, and penis (groin
      region). Histomorphologic testing showed mild to dense perivascular and
      periadnexal lymphoid aggregates throughout the dermis and extending into the
      panniculus, consistent with B-CLL. The diagnosis was confirmed with
      immunohistochemical studies that showed coexpression of CD5 and CD20 in the
      neoplastic lymphocytic infiltrate. LIMITATIONS: None. CONCLUSION: Cutaneous
      manifestations are an uncommon presentation of subclinical B-CLL. Cutaneous
      changes were the presenting features of underlying lymphoma in all 3 cases,
      highlighting the importance of maintaining a high index of suspicion for a
      lymphoproliferative process in cases with unusual or atypical clinicopathologic
      features. Additional investigations into the behavior of B-CLL in the skin may
      elucidate further the evolution of cutaneous lesions in this disease.

PMID- 19389521
TI  - Wet dressings used with topical corticosteroids for pruritic dermatoses: A
      retrospective study.
AB  - BACKGROUND: Wet dressings are a mainstay for initial management of pruritic adult
      dermatoses at Mayo Clinic, yet few recent reports describe their effectiveness
      for pruritic conditions other than atopic dermatitis in children. OBJECTIVE: To
      examine the effectiveness of wet dressings for pruritic dermatoses. METHODS: This
      is a retrospective study of adult patients admitted to our inpatient dermatology
      service between January 1, 2004, and August 31, 2007, treated with wet dressings
      and topical corticosteroids. Improvement was evaluated 1 day after admission and
      at dismissal. RESULTS: Three hundred thirty-one patients with pruritus (54 unique
      diagnoses) had 391 admissions. Improvement was reported for 146 (94%) of 156
      admissions at 1 day after admission and for 351 (98%) of 357 admissions at
      dismissal. LIMITATIONS: Retrospective nature of study. CONCLUSIONS: Wet dressings
      effectively alleviate recalcitrant pruritic dermatoses in adults. The lack of
      published reports on this treatment method suggests that wet dressings are
      underused.

PMID- 19389522
TI  - Minichromosome maintenance proteins are useful adjuncts to differentiate between
      benign and malignant melanocytic skin lesions.
AB  - BACKGROUND: Markers identifying premalignant and malignant melanocytic skin
      lesions are needed. OBJECTIVE: We aimed to investigate the protein expression of
      minichromosome maintenance (MCM) proteins in melanocytic skin lesions with
      different malignant potential. METHODS: Paraffin-embedded sections of benign
      melanocytic nevi (BN, n = 37), dysplastic nevi (DN, n = 25), and primary
      superficial spreading (SSM, n = 58) were assessed. Immunohistochemistry was
      performed for Ki-67, MCM3, MCM4, and MCM7 antibodies. RESULTS: Ki-67 expression
      of SSM was significantly increased when compared to DN (P = .0001) and BN (P =
      .0015). Compared to BN and DN, expression of MCM3 was significantly increased in
      SSM (P < .0001 and P = .019, respectively). MCM3 expression of DN was
      significantly increased as compared to BN (P = .0067). There was a significant
      correlation between MCM3 expression and Breslow tumor thickness (r = 0.44, P =
      .019). In SSM, MCM4 expression was significantly increased when compared with DN
      (P < .0001) and BN (P = .0033). MCM4 immunoreactivity was significantly higher in
      DN than in BN (P = .016). Immunohistology of MCM7 did not reveal significant
      differences between the groups investigated (P = .48). However, immunoreactivity
      of MCM7 significantly correlated with Breslow tumor thickness and Clark level (r
      = 0.39, P = .023; r = 0.44, P = .010, respectively). LIMITATIONS: Limitations of
      our study include the absence of survival data, mRNA results, and functional
      studies. CONCLUSIONS: MCM3 as well as MCM4 are differentially expressed in BN,
      DN, and SSM. Hence, immunolabeling of MCM3 and MCM4 proteins appears to be a
      promising additive tool for distinguishing benign from malignant melanocytic skin
      lesions.

PMID- 19389523
TI  - The superficial atypical Spitz tumor and malignant melanoma of superficial
      spreading type arising in association with the superficial atypical Spitz tumor:
      A distinct form of dysplastic Spitzoid nevomelanocytic proliferation.
AB  - Spitzoid lesions are diagnostically problematic because of a deceptive morphology
      and indeterminate behavior. The most problematic are atypical Spitz tumors
      whereby distinction from melanoma may be difficult. We have recognized a
      melanocytic lesion with a reproducible histomorphology, demonstrating
      characteristic demographic features, namely a predilection to involve younger
      female patients and common occurrence on the thigh. We have designated this
      lesion as the superficial atypical Spitz tumor and have encountered 27 cases. We
      believe that these lesions overlap histomorphologically with higher-grade
      dysplastic nevi and de novo intraepidermal epithelioid melanocytic dysplasia. We
      identified 19 additional cases that appear to represent transition into malignant
      melanoma of superficial spreading type arising in a background of the superficial
      atypical Spitz tumor. A limitation is that complete medical histories were not
      obtained for all patients. In conclusion, there exists a distinct subset of Spitz
      tumors that we designate as the superficial atypical Spitz tumor in which there
      is inherent dysplasia including lesions that evolve into melanoma of superficial
      spreading type.

PMID- 19389525
TI  - Carcinoma of the tongue.
AB  - Based on the dialogue "The tongue" between Janellen Smith, MD, and Gary Brauner,
      MD. Dialogues in Dermatology, a monthly audio program from the American Academy
      of Dermatology, contains discussions between dermatologists on timely topics.
      Commentaries from Dialogues Editor-in-Chief Warren R. Heymann, MD, are provided
      after each discussion as a topic summary and are provided here as a special
      service to readers of the Journal of the American Academy of Dermatology.

PMID- 19389524
TI  - Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus
      Conference.
AB  - BACKGROUND: Methotrexate remains a valuable option for the treatment of
      psoriasis. This report will summarize studies regarding the use of methotrexate
      since the last guidelines were published in 1998. OBJECTIVE: A task force of the
      National Psoriasis Foundation Medical Board was convened to evaluate treatment
      options. Our aim was to achieve a consensus on new updated guidelines for the use
      of methotrexate in the treatment of psoriasis. METHODS: Reports in the literature
      were reviewed regarding methotrexate therapy. RESULTS: A consensus was achieved
      on use of methotrexate in psoriasis including specific recommendations on dosing
      and monitoring. The consensus received unanimous approval from members of the
      Medical Board of the National Psoriasis Foundation. LIMITATIONS: There are few
      evidence-based studies on the treatment of psoriasis with methotrexate. Many of
      the reviewed reports are for the treatment of rheumatoid arthritis. CONCLUSIONS:
      Methotrexate is a safe and effective drug for the treatment of psoriasis.
      Appropriate patient selection and monitoring will significantly decrease the
      risks of side effects. In patients without risk factors for hepatic fibrosis,
      liver biopsies may not be indicated or the frequency of liver biopsies may be
      markedly reduced.

PMID- 19389526
TI  - Granuloma annulare-like skin lesions as an initial manifestation in a Japanese
      patient with adult T-cell leukemia/lymphoma.
AB  - Granuloma annulare is characterized by noncaseating dermal granulomas with
      connective tissue changes. A relationship with hematologic and solid malignancies
      has been suggested in some cases. We describe a 70-year-old man who had
      erythematous annular plaques on his elbows, upper extremities, and wrists for a
      period of 3 months. Histologic examination revealed epithelioid cell granulomas
      associated with dense atypical lymphocytes in the dermis. Immunohistochemical
      staining of skin specimens showed a prominent infiltration of CD3+, CD4+, CD5+,
      and CD25+ cells. Human T-cell leukemia virus type I proviral DNA was detected in
      the blood and cerebrospinal fluid by Southern blot analysis and polymerase chain
      reaction assay. The patient was given the diagnosis of adult T-cell
      leukemia/lymphoma based on the initial cutaneous manifestations. His condition
      progressed rapidly and led to his death. The granuloma annulare-like skin lesions
      in our patient could be considered as a peculiar immunologic hypersensitivity
      reaction of the host against the tumor cells or persistent human T-cell leukemia
      virus type I viral antigens. Dermatologists should be aware that this skin
      condition may be an initial manifestation of adult T-cell leukemia/lymphoma.

PMID- 19389527
TI  - Skin spicules: A newly described paraneoplastic phenomenon associated with a
      marginal zone B-cell lymphoma.
AB  - Paraneoplastic signs are an important clue to diagnosing an associated
      malignancy. We report an unusual variant of the sign of Leser-Trelat in a patient
      with a low-grade B-cell lymphoproliferative disorder and intertriginous skin
      spicules with histologic morphology of minute seborrheic keratoses.

PMID- 19389528
TI  - Lip plumper contact urticaria.
AB  - Lip plumpers are relatively new topical agents on the market that are designed to
      increase lip volume minutes to days after application. In this report, we
      describe a case of lip plumper contact urticaria in a young boy. We also discuss
      the mechanisms of action of lip plumpers and the sociocultural reasons for their
      use.

PMID- 19389529
TI  - Significant response after treatment with the mTOR inhibitor sirolimus in
      combination with carboplatin and paclitaxel in metastatic melanoma patients.
AB  - Melanoma is highly resistant to chemotherapy. In melanoma, the PI3K-AKT-mTOR
      signaling pathway is constitutively activated through multiple mechanisms.
      Several experimental studies suggest that targeting the PI3K-AKT-mTOR signaling
      pathway is a promising strategy to overcome chemoresistance. This is the first
      report describing a chemosensitizing effect of mTOR inhibition in patients with
      melanoma. We report two cases of patients with metastatic melanoma who showed
      significant remission after combination of carboplatin and paclitaxel with the
      mTOR inhibitor sirolimus. Our case report, together with the literature
      discussed, suggests that mTOR inhibition possibly enhances the sensitivity of
      melanoma cells to chemotherapy and should prompt in-depth and clinical
      investigation.

PMID- 19389530
TI  - Transient myeloproliferative disorder with vesiculopustular eruption: Early smear
      is useful for quick diagnosis.
AB  - We report a male infant with Down syndrome who had a transient myeloproliferative
      disorder associated with skin lesions. He was transferred to a neonatal intensive
      care unit because of low body weight, fetal edema, disseminated intravascular
      coagulation, and 10% blast cells in the peripheral blood. On postnatal day (PD)
      1, erythema with small papules, vesicles, and pustules appeared on the entire
      body. A smear preparation from the pustules on PD 2 showed 10% blast cells. A
      biopsy specimen taken on PD 5 revealed subcorneal pustules containing neutrophils
      and eosinophils. Genetic analyses detected a somatic mutation (197G>T,
      Glu295Stop) in exon 2 of GATA-1. On PD 10, the eruptions resolved spontaneously
      and the population of blast cells in peripheral blood decreased to 1%. The number
      of blast cells in pustules decreased markedly after three days. Therefore, we
      recommend that cytologic examination should be performed as early as possible.

PMID- 19389531
TI  - Sentinel node biopsy and standard of care for melanoma.
AB  - An international panel was convened by the organizing committee of the
      International Sentinel Node (SN) Society (ISNS) at their meeting in Sydney,
      Australia, on February 21, 2008, to address questions about SN biopsy (SNB) for
      melanoma. The panelists subsequently wrote this consensus statement, based on
      their interpretation of current evidence, as a guide to clinical treatment of
      patients with clinically localized melanoma. The panel comprised a cross section
      of expert melanoma surgeons who have contributed data and leadership to
      investigations of SNB.

PMID- 19389532
TI  - The significance of melanoma subsets.

PMID- 19389533
TI  - Guest authorship in the literature.

PMID- 19389534
TI  - Phototesting in solar urticaria.

PMID- 19389535
TI  - Continued use of home narrowband ultraviolet B light phototherapy for psoriasis
      after completion of a clinical trial.

PMID- 19389536
TI  - An exploratory study of adherence to topical benzoyl peroxide in patients with
      acne vulgaris.

PMID- 19389537
TI  - Acute onset of neurofibromas in association with esophageal adenocarcinoma.

PMID- 19389538
TI  - Iatrogenic hyperpigmentation in chronically infected hepatitis C patients treated
      with pegylated interferon and ribavirin.

PMID- 19389539
TI  - Severe hypoglycemia after initiation of anti-tumor necrosis factor therapy with
      etanercept in a patient with generalized pustular psoriasis and type 2 diabetes
      mellitus.

PMID- 19389540
TI  - An unusual clinical presentation of multiple tumors of the follicular
      infundibulum.

PMID- 19389541
TI  - A new case of neutrophilic sebaceous adenitis: A photodermatosis?

PMID- 19389545
TI  - [Descriptive analysis of basal cell carcinomas in patients aged more than 65
      years old undergoing surgery in Hospital Clinic in Granada (Spain) in 2007].

PMID- 19389546
TI  - Proteomics in laboratory medicine. Preface.

PMID- 19389547
TI  - Application of laser microdissection and reverse-phase protein microarrays to the
      molecular profiling of cancer signal pathway networks in the tissue
      microenvironment.
AB  - Laser-capture microdissection (LCM) is used to procure specific tissue cell
      subpopulations under direct microscopic visualization of a standard-stained
      frozen or fixed tissue section on a glass microscope slide. Protein microarrays
      can measure hundreds of analytes in a small input sample. A particular type of
      protein microarray, the reverse-phase array (RPA), is sensitive enough to
      accurately measure the small concentration of activated signal pathway molecules
      in microdissected tissue samples. This article explains how these two
      technologies, LCM and RPA, can be combined to yield molecular pathway data for
      the individualized therapy of the future.

PMID- 19389549
TI  - Autoantibody profiling for cancer detection.
AB  - Despite substantial progress in the understanding of the pathogenesis of cancer,
      the development and implementation of strategies for early cancer detection have
      lagged behind. Harnessing the immune response to tumor antigens is particularly
      useful for early detection because the immune response occurs early during tumor
      development and affords signal amplification with the end product, namely
      reactive immunoglobulins, being released into the circulation allowing easy
      access through the blood. This article presents recent developments in
      autoantibody profiling with a focus on proteomic approaches and applications to
      lung cancer.

PMID- 19389548
TI  - Microarrays in glycoproteomics research.
AB  - Microarrays have been extremely useful for investigating binding interactions
      among diverse types of molecular species, with the main advantage being the
      ability to examine many interactions using small amounts of samples and reagents.
      Microarrays are increasingly being used to advance research in the field of
      glycobiology. Several types of microarrays are being used in the study of glycans
      and proteins in glycobiology, including glycan arrays to study the recognition of
      carbohydrates, lectin arrays to determine carbohydrate expression on purified
      proteins or on cells, and antibody arrays to examine the variation in particular
      glycan structures on specific proteins. This article covers the technology and
      applications of these types of microarrays, and their use for obtaining
      complementary information on various aspects of glycobiology.

PMID- 19389550
TI  - Development and validation of a protein-based signature for the detection of
      ovarian cancer.
AB  - To overcome the significant mortality associated with ovarian cancer, a highly
      sensitive and specific screening test is urgently needed. CA-125 testing is used
      to monitor response to chemotherapy, detect recurrence, and detect late stage
      ovarian cancer. However, CA-125 testing, alone or in combination with
      ultrasonography, has not been adequate for early detection of ovarian cancer.
      This article discusses the authors' recent report of a novel multiplex assay that
      uses a panel of six serum biomarkers: leptin, prolactin, osteopontin, insulin
      like growth factor II (IGF-II), macrophage inhibitory factor (MIF), and CA-125.
      The combination of these six proteins yielded 95.3% sensitivity and 99.4%
      specificity. The application of this test in the clinical context and the most
      appropriate population, which could benefit from the test, are discussed.

PMID- 19389551
TI  - Analytical considerations for mass spectrometry profiling in serum biomarker
      discovery.
AB  - The potential of using mass spectrometry profiling as a diagnostic tool has been
      demonstrated for a wide variety of diseases. Various cancers and cancer-related
      diseases have been the focus of much of this work because of both the paucity of
      good diagnostic markers and the knowledge that early diagnosis is the most
      powerful weapon in treating cancer. The implementation of mass spectrometry as a
      routine diagnostic tool has proved to be difficult, however, primarily because of
      the stringent controls that are required for the method to be reproducible. The
      method is evolving as a powerful guide to the discovery of biomarkers that could,
      in turn, be used either individually or in an array or panel of tests for early
      disease detection. Using proteomic patterns to guide biomarker discovery and the
      possibility of deployment in the clinical laboratory environment on current
      instrumentation or in a hybrid technology has the possibility of being the early
      diagnosis tool that is needed.

PMID- 19389552
TI  - Salivary biomarkers for the detection of malignant tumors that are remote from
      the oral cavity.
AB  - Proteomic analyses by mass spectrometry are propelling the field of medical
      diagnostics forward at unprecedented rates because of its ability reliably to
      identify proteins that are at the femtomole level in concentration. These
      advancements have also benefited biomarker research to the point where saliva is
      now recognized as an excellent diagnostic medium for the detection of malignant
      tumors that are remote from the oral cavity. Saliva is easy to collect and may
      provide diagnostic information about a variety of cancers. In particular, proof
      of-principle has been demonstrated for salivary biomarker research. This article
      reviews the literature, discusses the theories associated with saliva-based tumor
      diagnostics, and presents the current research focused on the use of saliva as a
      diagnostic medium for the detection of cancer.

PMID- 19389553
TI  - Cardiovascular proteomics: implications for clinical applications.
AB  - Proteomics is fulfilling its potential and beginning to impact the diagnosis and
      therapy of cardiovascular disease. As de novo proteomics analysis gets more
      streamlined, and robust high-throughput methods are developed, more and more
      attention is being directed toward the field of cardiovascular serum and plasma
      biomarker discovery. To take cardiovascular proteomics from bench to bedside,
      great care must be taken to achieve reproducible results. Despite technical
      advances, however, the absolute number of clinical biomarkers thus far discovered
      by a proteomics approach is small. Although several factors contribute to this
      lack, one step is to build "translation teams" involving a close collaboration
      between researchers and clinicians.

PMID- 19389554
TI  - Clinical proteomic applications of formalin-fixed paraffin-embedded tissues.
AB  - Although proteomic technology has proved to be extremely powerful in basic
      research, its impact has not been as great in the clinical laboratory. The
      future, however, looks extremely positive because technologies, such as mass
      spectrometry and tissue microarrays, have continued to improve over the past
      several years. One of the most exciting developments, particularly in the area of
      mass spectrometry, is the ability to examine formalin-fixed paraffin-embedded
      tissue using these technologies. The almost inexhaustible supply of these tissues
      will enable proteomic laboratories access to clinically important specimens that
      will undoubtedly lead to a number of important discoveries in the near future.

PMID- 19389555
TI  - Development of high-throughput mass spectrometry-based approaches for cancer
      biomarker discovery and implementation.
AB  - A major goal of cancer research is elucidating the molecular events underlying
      carcinogenesis, with the goal of discovering better diagnostic markers and
      therapeutic targets. Proteomics aims to facilitate this process by applying newly
      developed methods and advanced analytic tools, such as mass spectrometry, for the
      investigation of the protein complement en masse. Proteomics is the comprehensive
      study of proteins and is aimed at analyzing their structure, function,
      modifications, expression, interactions, and localization in complex biological
      systems. This article reviews the state-of-the art in mass spectrometry-based
      approaches and their application for cancer biomarker discovery and validation.

PMID- 19389556
TI  - Proteomics and diabetic retinopathy.
AB  - Despite significant research on many fronts, the global diabetes pandemic and its
      attendant complications remains complex and poorly understood. Proteomic
      approaches have been used to deal with these complexities through methods to
      increase the fractional abundance of low-abundant proteins, and to compare
      protein samples directly using either chemical labeling methods or label-free
      methods to identify and comparatively analyze proteins directly in the mass
      spectrometer. It is more likely that a single protein does not initiate disease
      progression but rather multiple vitreous-resident serum proteins likely
      contribute to the pathogenic mechanisms. Substantial work remains to understand
      better the initiation and progression of nonproliferative diabetic retinopathy,
      proliferative diabetic retinopathy, and diabetic macular edema in the context of
      why some type-1 diabetics and why many type-2 diabetics do not progress toward
      loss of vision and blindness.

PMID- 19389558
TI  - Five-year follow-up after sirolimus-eluting stent implantation results of the
      SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) Trial.
AB  - OBJECTIVES: The aim of this study was to examine the 5-year clinical safety and
      efficacy outcomes in patients enrolled in the SIRIUS (Sirolimus-Eluting Stent in
      De-Novo Native Coronary Lesions) trial. BACKGROUND: The SIRIUS trial was a double
      blinded randomized study that demonstrated that sirolimus-eluting stents (SES)
      significantly improved angiographic results (at 8 months) and clinical outcomes
      (at 9 and 12 months) compared with bare-metal stents (BMS). METHODS: Patients (n
      = 1,058) with de novo native coronary artery lesions were randomized to either
      SES (n = 533) or control BMS (n = 525) and were followed for 5 years. RESULTS:
      Between 1 and 5 years, additional clinical events were similarly distributed
      among the sirolimus and control groups. At 5 years, in sirolimus versus control
      patients, target lesion revascularization was 9.4% versus 24.2% (p < 0.001) and
      major adverse cardiovascular events and target vessel failure rates were 20.3%
      versus 33.5% and 22.5% versus 33.5%, respectively (p < 0.0001 for both). There
      were no significant differences in death, myocardial infarction, and nontarget
      lesion revascularization. No significant differences were observed in the
      cumulative incidence of stent thrombosis for sirolimus versus control patients
      with either protocol-derived (1.0% vs. 0.8%) or Academic Research Consortium
      definitions (3.9% vs. 4.2%). CONCLUSIONS: In patients with noncomplex coronary
      artery disease, clinical outcomes 5 years after implantation of SES continue to
      demonstrate significant reduction in the need for repeat revascularization, with
      similar safety (death and myocardial infarction) compared with BMS, without
      evidence for either disproportionate late restenosis or late stent thrombosis.

PMID- 19389559
TI  - Acute left ventricular dynamic effects of primary percutaneous coronary
      intervention from occlusion to reperfusion.
AB  - OBJECTIVES: We studied the left ventricular (LV) dynamic effects of primary
      percutaneous coronary intervention (PCI) for ST-segment elevation myocardial
      infarction (STEMI) by directly obtaining pressure-volume (PV) loops during the
      procedure. BACKGROUND: An acute myocardial infarction causes a decrease in LV
      compliance. The instantaneous effects of primary PCI on LV compliance are
      unknown. METHODS: We studied 15 consecutive patients (10 males, ages 59 +/- 12
      years), who presented with their first acute anterior STEMI within 6 h after
      onset of symptoms, and in whom coronary angiography revealed an occluded left
      anterior descending coronary artery. Before performing primary PCI, we inserted a
      pressure-conductance catheter in the LV to continuously obtain PV loops. RESULTS:
      Immediately after successful reperfusion, significant improvements were observed
      in LV diastolic function, as indicated by an increased end-diastolic compliance
      with a 6.0 +/- 2.8 mm Hg (p < 0.0001) downward shift of the compliance curve.
      There was a decrease in end-diastolic pressure of 24 +/- 18% (p = 0.0002), in
      stiffness of 27 +/- 18% (p = 0.0003), and in wall stress of 20 +/- 24% (p =
      0.004). Systolic function mainly showed an immediate improvement in apical
      contractility from 40 +/- 17% to 54 +/- 15% (p = 0.01). CONCLUSIONS: Primary PCI
      in anterior STEMI patients causes an immediate improvement in diastolic function,
      assessed by online PV loop measurements.

PMID- 19389557
TI  - Cardiovascular magnetic resonance in myocarditis: A JACC White Paper.
AB  - Cardiovascular magnetic resonance (CMR) has become the primary tool for
      noninvasive assessment of myocardial inflammation in patients with suspected
      myocarditis. The International Consensus Group on CMR Diagnosis of Myocarditis
      was founded in 2006 to achieve consensus among CMR experts and develop
      recommendations on the current state-of-the-art use of CMR for myocarditis. The
      recommendations include indications for CMR in patients with suspected
      myocarditis, CMR protocol standards, terminology for reporting CMR findings, and
      diagnostic CMR criteria for myocarditis (i.e., "Lake Louise Criteria").

PMID- 19389560
TI  - Baseline Q-wave surpasses time from symptom onset as a prognostic marker in ST
      segment elevation myocardial infarction patients treated with primary
      percutaneous coronary intervention.
AB  - OBJECTIVES: We assessed the incremental value of baseline Q waves over time from
      symptom onset as a marker of clinical outcome in ST-segment elevation myocardial
      infarction (STEMI). BACKGROUND: Time from symptom onset is a central focus in
      STEMI patients. The presence of Q waves on the baseline electrocardiogram (ECG)
      has been suggested to be of incremental value to time from symptom onset in
      evaluating clinical outcomes. METHODS: We evaluated baseline Q waves and ST
      segment resolution 30 min after primary percutaneous intervention (PCI) ECGs in
      4,530 STEMI patients without prior infarction. Additionally, peak biomarkers; 90
      day mortality; and the composite of death, congestive heart failure (CHF), or
      cardiogenic shock were assessed. RESULTS: Fifty-six percent of patients had
      baseline Q waves: they were older, more frequently male and diabetic, and had a
      more advanced Killip class. Patients with baseline Q waves had greater mortality
      and a higher composite rate of death, CHF, and shock versus patients without
      baseline Q waves at 90 days (5.3% vs. 2.1% and 12.1% vs. 4.8%, respectively, both
      p < 0.001). Complete ST-segment resolution was highest, whereas 90-day mortality
      and the composite outcome were lowest among those randomized < or =3 h without
      baseline Q waves. After multivariable adjustment, baseline Q-wave but not time
      from symptom onset was significantly associated with a 78% relative increase in
      the hazard of 90-day mortality and a 90% relative increase in the hazard of
      death, shock, and CHF. CONCLUSIONS: Baseline Q waves in STEMI patients treated
      with primary PCI provide an independent prognostic marker of clinical outcome.
      These data might be useful in designing future clinical trials as well as in
      evaluating patients for triage and potential transfer for planned primary PCI.
      (Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction [APEX
      AMI]; NCT00091637).

PMID- 19389561
TI  - Efficacy of ranolazine in patients with chronic angina observations from the
      randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency
      With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary
      Syndromes) 36 Trial.
AB  - OBJECTIVES: We aimed to evaluate the efficacy and safety of ranolazine in a
      larger and more diverse group of patients with angina than previously studied.
      BACKGROUND: Ranolazine is an antianginal shown to reduce angina and improve
      exercise performance in selected patients with early-positive exercise testing
      and those with frequent angina. METHODS: We investigated the antianginal effects
      of ranolazine in the subgroup of patients with prior chronic angina (n = 3,565,
      54%) enrolled in the randomized, double-blind, placebo-controlled MERLIN-TIMI
      (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute
      Coronary Syndromes) 36 trial of patients with acute coronary syndrome. Follow-up
      was a median of 350 days. RESULTS: Patients with prior angina received evidence
      based therapy (95% aspirin, 78% statins, 89% beta-blockers, average 2.9
      antianginal agents). The primary end point (cardiovascular death, myocardial
      infarction, recurrent ischemia) was less frequent with ranolazine (hazard ratio
      [HR]: 0.86; 95% confidence interval [CI]: 0.75 to 0.97; p = 0.017), due entirely
      to a significant reduction in recurrent ischemia (HR: 0.78; 95% CI: 0.67 to 0.91;
      p = 0.002). Ranolazine also reduced worsening angina (HR: 0.77; 95% CI: 0.59 to
      1.00; p = 0.048) and intensification of antianginal therapy (HR: 0.77; 95% CI:
      0.64 to 0.92, p = 0.005). Exercise duration at 8 months was greater with
      ranolazine (514 s vs. 482 s, p = 0.002). Cardiovascular death or myocardial
      infarction did not differ between treatment groups (HR: 0.97; 95% CI: 0.80 to
      1.16; p = 0.71). Symptomatic documented arrhythmias (2.9% vs. 2.9%, p = 0.92) and
      total mortality (6.2% vs. 6.4%, p = 0.96) were similar with ranolazine or
      placebo. CONCLUSIONS: In this largest study of ranolazine in patients with
      established coronary artery disease, ranolazine was effective in reducing angina
      with favorable safety in a substantially broader group of patients with angina
      than previously studied. (Metabolic Efficiency With Ranolazine for Less Ischemia
      in Non-ST Elevation Acute Coronary Syndromes; NCT00099788).

PMID- 19389562
TI  - Thin-walled microvessels in human coronary atherosclerotic plaques show
      incomplete endothelial junctions relevance of compromised structural integrity
      for intraplaque microvascular leakage.
AB  - OBJECTIVES: This study sought to examine the ultrastructure of microvessels in
      normal and atherosclerotic coronary arteries and its association with plaque
      phenotype. BACKGROUND: Microvessels in atherosclerotic plaques are an entry point
      for inflammatory and red blood cells; yet, there are limited data on the
      ultrastructural integrity of microvessels in human atherosclerosis. METHODS:
      Microvessel density (MVD) and ultrastructural morphology were determined in the
      adventitia, intima-media border, and atherosclerotic plaque of 28 coronary
      arteries using immunohistochemistry for endothelial cells (Ulex europeaus,
      CD31/CD34), basement membrane (laminin, collagen IV), and mural cells (desmin,
      alpha-smooth muscle [SM] actin, smoothelin, SM1, SM2, SMemb). Ultrastructural
      characterization of microvessel morphology was performed by electron microscopy.
      RESULTS: The MVD was increased in advanced plaques compared with early plaques,
      which correlated with lesion morphology. Adventitial MVD was higher than
      intraplaque MVD in normal arteries and early plaques, but adventitial and
      intraplaque MVD were similar in advanced plaques. Although microvessel basement
      membranes were intact, the percentage of thin-walled microvessels was similarly
      low in normal and atherosclerotic adventitia, in the adventitia and the plaque,
      and in all plaque types. Intraplaque microvascular endothelial cells (ECs) were
      abnormal, with membrane blebs, intracytoplasmic vacuoles, open EC-EC junctions,
      and basement membrane detachment. Leukocyte infiltration was frequently observed
      by electron microscopy, and confirmed by CD45RO and CD68 immunohistochemistry.
      CONCLUSIONS: The MVD was associated with coronary plaque progression and
      morphology. Microvessels were thin-walled in normal and atherosclerotic arteries,
      and the compromised structural integrity of microvascular endothelium may explain
      the microvascular leakage responsible for intraplaque hemorrhage in advanced
      human coronary atherosclerosis.

PMID- 19389563
TI  - Intrusion through the fragile back door: immature plaque microvessels as entry
      portals for leukocytes and erythrocytes in atherosclerosis.

PMID- 19389564
TI  - Nebivolol, a vasodilating selective beta(1)-blocker, is a beta(3)-adrenoceptor
      agonist in the nonfailing transplanted human heart.
AB  - OBJECTIVES: The present study was to assess whether nebivolol could activate
      beta(3)-adrenergic receptors (ARs) in the human heart. BACKGROUND: Nebivolol is a
      third-generation beta-blocker used in the treatment of heart failure. It
      associates selective beta(1)-adrenergic antagonist properties with endothelial
      and nitric oxide (NO)-dependent vasodilation. Several studies reported that this
      vasodilation could result from an activation of beta(3)-ARs, but no data are
      available in the heart. METHODS: The effect of nebivolol (0.1 nmol/l to 10
      micromol/l) upon the developed peak tension was tested in endomyocardial biopsies
      from human nonrejecting transplanted hearts. Tension was recorded at steady state
      using a mechanoelectric force transducer. RESULTS: Nebivolol induced a
      concentration-dependent decrease in peak tension (maximum effect obtained at 10
      micromol/l: -55 +/- 4%, n = 6), which was similar to that obtained with a
      preferential beta(3)-AR agonist, BRL 37344 (maximum effect obtained at 1
      micromol/l: -45 +/- 2%, n = 12). The nebivolol effect was not modified by 10
      micromol/l nadolol, a beta(1,2)-AR antagonist, but was significantly reduced in
      the presence of 1 micromol/l L-748,337, a selective beta(3)-AR antagonist, and
      after pre-treatment with 100 micromol/l N(G)-monomethyl-L-arginine, an NOS
      inhibitor. CONCLUSIONS: Our study demonstrated that nebivolol activated beta(3)
      AR in the human ventricle. The NO-dependent negative inotropic effect of
      nebivolol associated with its vasodilating properties previously described in
      human microcoronary arteries could improve the energetic balance in heart. Those
      effects could explain the improvement of hemodynamic parameters obtained in
      patients with heart failure after nebivolol administration as previously
      described in clinical trials.

PMID- 19389565
TI  - beta(3)-Adrenoceptor stimulation on top of beta(1)-adrenoceptor blockade "Stop or
      Encore?".

PMID- 19389566
TI  - Real-time 3-dimensional transesophageal echocardiography in the evaluation of
      post-operative mitral annuloplasty ring and prosthetic valve dehiscence.
AB  - OBJECTIVES: This study sought to assess the use of real-time (RT) 3-dimensional
      (3D) transthoracic and transesophageal echocardiography (TEE) in the evaluation
      of post-operative mitral valve dehiscence. BACKGROUND: Mitral valve replacement
      or repair may be complicated by post-operative dehiscence of the valve or
      annuloplasty ring resulting in clinically significant mitral regurgitation or
      hemolysis. Diagnosis is generally performed using 2-dimensional transthoracic
      echocardiography and TEE. Recently, an RT 3D TEE probe has been developed to
      produce high-quality real-time images. METHODS: We used RT 3D TEE to evaluate
      mitral regurgitation after mitral valve repair or replacement as a result of
      mitral ring dehiscence. We studied the additional information and diagnostic
      utility provided by RT 3D TEE. RESULTS: Eighteen patients were studied (8
      patients after repair and 10 after replacement). Real-time 3D TEE allowed
      accurate evaluation of the pathology, including definition of the type of ring or
      prosthesis used; description of the site, size, shape, and area of the dehisced
      segment; and clear definition of the origin of the mitral regurgitation.
      CONCLUSIONS: In mitral valve dehiscence, RT 3D TEE provides additional
      information about the exact anatomic characteristics of the dehiscence that can
      be used to help in planning the most appropriate corrective intervention.

PMID- 19389568
TI  - Ventilatory efficiency and aerobic capacity predict event-free survival in adults
      with atrial repair for complete transposition of the great arteries.

PMID- 19389567
TI  - Ventilatory efficiency and aerobic capacity predict event-free survival in adults
      with atrial repair for complete transposition of the great arteries.
AB  - OBJECTIVES: The goal of this study was to assess the prognostic value of the
      cardiopulmonary exercise test (CPET) in patients who received a Mustard and
      Senning (M/S) operation. BACKGROUND: Patients who received an M/S operation have
      increased long-term risk of cardiovascular morbidity and mortality. Limited
      information is available on how to stratify risk in this population. METHODS:
      Between 1996 and 2007, 274 adults (age 26.3 +/- 8.9 years, range 16 to 50 years)
      who had received a Mustard (n = 144) or Senning (n = 130) operation in infancy
      were studied with CPET. During a follow-up of 3.9 +/- 2.3 years (range 0.2 to
      10.8 years), 12 patients died at an age of 36 +/- 14 years, and 46 patients
      required a cardiac-related emergency (<24 h from the onset of symptom/condition)
      hospital admission at an age of 30 +/- 11 years. RESULTS: At multivariate Cox
      analysis, the slope of ventilation per unit of carbon dioxide output (VE/VCO(2)
      slope) (hazard ratio: 1.088, p < 0.0001) and percentage of predicted peak oxygen
      uptake (Vo(2)%) (hazard ratio: 0.979, p = 0.0136) were the strongest predictors
      of death/cardiac-related emergency hospital admission among demographic,
      clinical, and exercise variables. A VE/VCO(2) slope > or =35.4 (hazard ratio:
      10.7, 95% confidence interval [CI]: 7.8 to 24.6), and a peak Vo(2)% < or =52.3%
      (hazard ratio: 3.4, 95% CI: 2.5 to 8.2) were associated with an increased 4-year
      risk of death/cardiac-related emergency hospital admission. Patients who had both
      a VE/VCO(2) slope > or =35.4 and a peak Vo(2)% < or =52.3% of predicted value
      were at highest risk (4-year event rate: 78.8%). CONCLUSIONS: CPET provides
      important prognostic information in adults with M/S operation. Subjects with
      enhanced ventilatory response to exercise or those with poor exercise capacity
      have a substantially higher 4-year risk of death/cardiac-related emergency
      hospital admission.

PMID- 19389569
TI  - The year in echocardiography.

PMID- 19389570
TI  - Ebstein anomaly by cardiac magnetic resonance imaging.

PMID- 19389571
TI  - Brugada syndrome or Brugada electrocardiogram?

PMID- 19389573
TI  - Left dominant arrhythmogenic cardiomyopathy a new clinical entity without a
      typical substrate of myocardial damage.

PMID- 19389575
TI  - ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the
      American College of Cardiology Foundation Task Force on Expert Consensus
      Documents and the American Heart Association developed in collaboration with the
      American College of Chest Physicians; American Thoracic Society, Inc.; and the
      Pulmonary Hypertension Association.

PMID- 19389576
TI  - Foreword: psychoneuroimmunology--the essence of a three's company.

PMID- 19389577
TI  - Psychoneuroimmunology. Preface.

PMID- 19389578
TI  - The blood-brain barrier in psychoneuroimmunology.
AB  - The term ''psychoneuroimmunology'' connotes separate compartments that interact.
      The blood-brain barrier (BBB) is both the dividing line, physical and
      physiologic, between the immune system and the central nervous system (CNS) and
      the locale for interaction. The BBB restricts unregulated mixing of immune
      substances in the blood with those in the CNS, directly transports neuroimmune
      active substances between the blood and CNS, and itself secretes neuroimmune
      substances. These normal functions of the BBB can be altered by neuroimmune
      events. As such, the BBB is an important conduit in the communication between the
      immune system and the CNS.

PMID- 19389579
TI  - Molecular aspects of fever and hyperthermia.
AB  - After defining hyperthermia and fever, this article describes the complete chain
      of events leading to the genesis of fever, starting with the lipopolysaccharide
      induced formation of endogenous pyrogens (cytokines), their interactions with
      relevant targets in the brain, the induction of enzymes responsible for the
      formation of prostaglandin E2, the activation of descending neuronal pathways via
      the EP3 receptor, and the stimulation of thermogenesis via this pathway to
      support the febrile shift of the thermoregulatory set point. This article also
      summarizes an alternative hypothesis to account for a rapid induction of the
      early phase of lipopolysaccharide-induced fever before the release of larger
      amounts of cytokines into the bloodstream. Other topics discussed include
      malignant hypothermia, drug-induced hypothermia, and the heat stroke syndrome.

PMID- 19389581
TI  - Hypothalamo-pituitary-adrenocortical axis, glucocorticoids, and neurologic
      disease.
AB  - Neurologic diseases are often accompanied by significant life stress and
      consequent increases in stress hormone levels. Glucocorticoid stress hormones are
      known to have deleterious interactions with neurodegenerative processes, and are
      hypersecreted in neurologic disorders as well as in comorbid psychiatric
      conditions, such as depression. This article highlights the state of our
      knowledge on mechanisms controlling activation and inhibition of glucocorticoid
      secretion, outlines signaling mechanisms used by these hormones in neural tissue,
      and describes how endogenous glucocorticoids can mediate neuronal damage in
      various models of neurologic disease. The article highlights the importance of
      controlling stress and consequent stress hormone secretion in the context of
      neurologic disease states.

PMID- 19389580
TI  - Cytokine, sickness behavior, and depression.
AB  - The psychologic and behavioral components of sickness represent, together with
      fever response and associated neuroendocrine changes, a highly organized strategy
      of the organism to fight infection. This strategy, referred to as sickness
      behavior, is triggered by the proinflammatory cytokines produced by activated
      cells of the innate immune system in contact with specific pathogen-associated
      molecular patterns (PAMPs). Interleukin-1 and other cytokines act on the brain
      via (1) a neural route represented by the primary afferent neurons that innervate
      the body site where the infectious process takes place and (2) a humoral pathway
      that involves the production of proinflammatory cytokines. This article presents
      the current knowledge on the way this communication system is organized and
      regulated and the implications of these advances for understanding brain
      physiology and pathology.

PMID- 19389582
TI  - Social interactions, stress, and immunity.
AB  - This article summarizes the endocrine and immune changes induced by an
      experimental model for social stress characterized by repeated defeat. Data
      indicate that mice facing a social stressor may use different behavioral coping
      responses based on the environmental conditions and previous experiences.
      Although chronic stressors generally suppress immune function and increase a
      host's susceptibility to disease, this may not be always true in all cases. For
      example, under conditions in which individuals face the chance of being injured
      repeatedly, it may be an adaptive advantage to maintain or even enhance an immune
      response. The development of glucocorticoid resistance after social disruption
      may be such a mechanism, allowing animals to heal injuries and clear invading
      microbes in the presence of the anti-inflammatory stress hormones.

PMID- 19389583
TI  - Sleep and psychoneuroimmunology.
AB  - The brain uses a variety of mechanisms to survey the immune system constantly.
      Responses of the immune system to invading pathogens are detected by the central
      nervous system, which responds by orchestrating complex changes in behavior and
      physiology. Sleep is one of the behaviors altered in response to immune
      challenge. The role of cytokines as mediators of responses to infectious
      challenge and regulators and modulators of sleep is the focus of this article.

PMID- 19389584
TI  - Depression and immunity: inflammation and depressive symptoms in multiple
      sclerosis.
AB  - An increasing body of evidence suggests that patients who have major depressive
      disorder show alterations in immunologic markers including increases in
      proinflammatory cytokine activity and inflammation. Inflammation of the central
      nervous system is a pathologic hallmark of multiple sclerosis (MS). Patients
      affected by this disease also show a high incidence of depression. Accumulating
      evidence from animal studies suggests that some aspects of depression and fatigue
      in MS may be linked to inflammatory markers. This article reviews the current
      knowledge in the field and illustrates how the sickness behavior model may be
      applied to investigate depressive symptoms in inflammatory neurologic diseases.

PMID- 19389585
TI  - Age and neuroinflammation: a lifetime of psychoneuroimmune consequences.
AB  - Aging can impair functional interaction that occurs between the brain and the
      immune system. Recent findings indicate that microglia and astrocytes, innate
      immune cells of the brain, become more reactive during normal aging. This age
      associated increase in innate immune reactivity sets the stage for an exaggerated
      inflammatory cytokine response in the brain after activation of the peripheral
      innate immune system. This elevated neuroinflammatory response may lead to more
      severe long-lasting behavioral and cognitive deficits. This article discusses new
      evidence that aging creates a brain environment that is permissive to the
      occurrence of mental health complications following innate immune activation.

PMID- 19389587
TI  - Psychoneuroimmunology of stroke.
AB  - Stroke is the major cause of disability in the Western world and is the third
      greatest cause of death, but there are no widely effective treatments to prevent
      the devastating effects of stroke. Extensive and growing evidence implicates
      inflammatory and immune processes in the occurrence of stroke and particularly in
      the subsequent injury. Several inflammatory mediators have been identified in the
      pathogenesis of stroke including specific cytokines, adhesion molecules, matrix
      metalloproteinases, and eicosanoids. An early clinical trial suggests that
      inhibiting interleukin-1 may be of benefit in the treatment of acute stroke.

PMID- 19389586
TI  - Psychoneuroimmune implications of type 2 diabetes: redux.
AB  - A sizable body of knowledge has arisen demonstrating that type 2 diabetes (T2D)
      is associated with alterations in the innate immune system. The resulting
      proinflammatory-leaning imbalance is implicated in the development of secondary
      disease complications and comorbidities, such as delayed wound healing,
      accelerated progress of atherosclerosis, and retinopathy, in people who have T2D.
      New experimental data and the results of recently published health-related
      quality-of-life surveys indicate that individuals who have T2D experience
      diminished feelings of happiness, well being, and satisfaction with life. These
      emotional and psychological consequences of T2D point to altered neuroimmunity as
      a previously unappreciated complication of T2D. This article discusses recent
      data detailing the impact of T2D on a person's PNI response.

PMID- 19389588
TI  - Exercise, inflammation, and innate immunity.
AB  - Exercise has beneficial effects on chronic disease, and the drive to understand
      the mechanisms of these benefits is strong. This article presents several
      compelling potential mechanisms for the anti-inflammatory effect of exercise,
      including reduced percentage of body fat and macrophage accumulation in adipose
      tissue, muscle-released interleukin-6 inhibition of tumor necrosis factor-a, and
      the cholinergic anti-inflammatory pathway.

PMID- 19389589
TI  - Update on ankle arthritis: foreword.

PMID- 19389590
TI  - Management of ankle arthritis. Preface.

PMID- 19389591
TI  - Osteoarthritis of the ankle: bridging concepts in basic science with clinical
      care.
AB  - Trends in science are beginning to suggest that cartilage degeneration may be
      related to a chronic imbalance in extracellular matrix metabolism. In cartilage,
      a combination of biomechanical, biochemical, and matrix-related signaling
      pathways regulates the equilibrium between cartilage anabolism and catabolism. A
      potential limitation of many current treatments of osteoarthritis is that they
      may not comprehensively restore regulation of a balance between cartilage
      anabolism and catabolism.

PMID- 19389592
TI  - MRI evaluation of ankle distraction: a preliminary report.
AB  - Ankle joint distraction has been shown to be a viable alternative to ankle
      arthrodesis or ankle replacement. The authors' approach to ankle joint
      preservation includes articulated ankle joint distraction, resection of blocking
      osteophytes, release of muscle and joint contractures, and realignment osseous
      ankle procedures. In a previous study that used this technique, 78% of patients
      maintained their ankle range of motion and had none to occasional moderate pain
      that could be managed generally with nonsteroid anti-inflammatory drugs alone.
      The rationale as to why joint distraction is successful is largely unknown.
      Therefore, the purpose of this study was to evaluate pre- and postoperative ankle
      MRI scans of patients who underwent hinged ankle joint distraction with external
      fixation.

PMID- 19389593
TI  - Brace management for ankle arthritis.
AB  - Management of ankle arthritis can be difficult for the physician and patient.
      Conservative options are limited but should be exhausted in an effort to prolong
      ankle arthrodesis. Custom braces can provide an effective means to alleviate
      pain, improve quality of life, and prolong ankle arthrodesis in patients affected
      by advanced ankle arthritis with or without deformity.

PMID- 19389594
TI  - Update on viscosupplementation in the treatment of osteoarthritis of the foot and
      ankle.
AB  - In the recent past, nonsurgical treatment of osteoarthritis was limited to rest,
      immobilization, physical therapy, activity modifications, nonsteroidal anti
      inflammatory drugs, analgesics, weight loss, assistive devices for walking, and
      corticosteroid injections. Viscosupplementation is a welcome addition to the
      nonsurgical armamentarium available to physicians. It is used to introduce
      hyaluronic acid into the joint to provide initial lubrication and shock
      absorption, and to change the long-term disease process. This article discusses
      the pathology of osteoarthritis; the characteristics, physiology, and
      administration of commercial viscosupplements; and reviews the research on
      hyaluronic acid use in the foot and ankle. It concludes that additional studies
      are required to test the safety and efficacy of this treatment in other parts of
      the foot.

PMID- 19389596
TI  - Ankle arthrodiastasis.
AB  - Ankle joint distraction, or arthrodiastasis, has emerged as a viable treatment
      alternative for recalcitrant ankle arthritis. This joint salvage procedure avoids
      the potential complications associated with joint arthrodesis or joint
      arthroplasty in the young patient population typically affected by posttraumatic
      ankle arthritis. The treatment is predicated on the knowledge that osteoarthritic
      ankle cartilage is capable of repair. The reparative capacity of the ankle
      chondrocyte is enhanced through the mechanical offloading of the joint and
      maintenance of intra-articular fluid pressure changes. Scientific data
      demonstrate positive biochemical and biomechanical intra-articular changes
      associated with joint distraction, facilitating an environment for cartilage
      repair. Clinical studies, although limited, have resulted in significant patient
      benefit in the short-term and long-term treatment of arthritis. Further studies
      are needed to evaluate this technique and its ideal indication. Current
      literature does support its use in the treatment of ankle arthritis, however.

PMID- 19389595
TI  - A review of osteochondral lesions of the talus.
AB  - This article provides an in-depth overview of the most current information.

PMID- 19389597
TI  - Supramalleolar osteotomy.
AB  - Supramalleolar osteotomy for posttraumatic malunion, developmental or physeal
      deformities, congenital malalignment, or focal articular degenerative problems in
      the ankle is a useful surgical technique. Accurate evaluation of the distal
      tibial deformity, weight-bearing radiographs, and soft tissue examination for
      contractures and instability ensure proper decision making. Osteotomy planning
      must involve all components of the deformity, including the foot, and respect
      osteotomy principles.

PMID- 19389598
TI  - Traditional ankle arthrodesis for the treatment of ankle arthritis.

PMID- 19389599
TI  - Arthroscopic ankle arthrodesis.
AB  - Arthroscopic ankle arthrodesis provides the foot and ankle surgeon with an
      alternative to traditional open techniques. Advancements in arthroscopic
      techniques and instrumentation have made the procedure easier to perform.
      Advantages include faster rates of union, decreased complications, reduced
      postoperative pain, shorter hospital stays, minimal loss of length of the lower
      limb, and minimal clinical deformity or shapechanges to the ankle. This article
      reviews the literature on the subject and discusses the procedure's indications
      and contraindications, and surgical technique. It concludes that while total
      ankle replacement continues to grow in popularity, arthroscopic ankle arthrodesis
      is a viable alternative for management of the end-stage arthritic ankle.

PMID- 19389600
TI  - Tibiotalocalcaneal arthrodesis for salvage of severe ankle degeneration.
AB  - Tibiotalocalcaneal arthrodesis is a successful and proven surgical procedure for
      patients who have significant arthritic changes, deformity, and failed previous
      operations. Surgical technique varies depending on the type of fixation. Basic
      surgical principles should not be violated. Correction of the deformity with
      appropriate joint preparation and stable fixation is important for a good
      outcome. Other adjunctive materials, such as bone growth stimulators and
      orthobiologics, should be used appropriately to ensure adequate primary
      arthrodesis.

PMID- 19389601
TI  - Total ankle arthroplasty: indications and avoiding complications.
AB  - New designs and a better understanding of kinematics, patient selection, and
      surgical techniques have lead to a rejuvenated interest in total ankle
      arthroplasty (TAA). Although improved design has decreased the frequency of
      revision, the causes and inherent difficulty associated with TAA remain
      challenging. Surgeon experience and proper patient selection are consistently the
      most important factors in fostering favorable outcomes.

PMID- 19389602
TI  - Combined medial displacement calcaneal osteotomy, subtalar joint arthrodesis, and
      ankle arthrodiastasis for end-stage posterior tibial tendon dysfunction.
AB  - Combining an ankle arthrodiastasis with a medial displacement calcaneal osteotomy
      and a subtalar joint arthrodesis offers surgeons a joint-sparing procedure for
      young and active patients who have end-stage posterior tibial tendon dysfunction
      and ankle joint involvement. An isolated subtalar joint arthrodesis or triple
      arthrodesis combined with an ankle arthrodiastasis is an option that can be used
      in certain case scenarios. Delaying the need for a joint destructive procedure
      through an ankle arthrodiastasis, however, may have a great impact in the near
      future, as advancements are underway to improve the use of ankle endoprosthesis.

PMID- 19389603
TI  - A case report of a simultaneous local osteochondral autografting and ankle
      arthrodiastasis for the treatment of a talar dome defect.
AB  - Talar osteochondral defects (OCDs) are a challenge for treating physicians
      because they frequently are missed or diagnosed incorrectly, often resulting in
      severe degenerative arthritis of the ankle joint. Surgical intervention becomes a
      viable option in the presence of larger OCDs associated with loose bodies or
      osteochondral lesions that have failed conservative treatment. The successful use
      of autologous osteochondral autograft in the knee has promoted the applicability
      in the ankle. This report describes a unique technique for the treatment of large
      talar osteochondral lesions using a local osteochondral autograft combined with
      an ankle arthrodiastasis.

PMID- 19389604
TI  - Differences in physical characteristics and response to rehabilitation for
      patients with hand dystonia: musicians' cramp compared to writers' cramp.
AB  - STUDY DESIGN: Pre-Post, Mixed Factorial Trial. INTRODUCTION: Focal hand dystonia
      is a challenging movement disorder to rehabilitate in musicians and writers.
      PURPOSE OF THE STUDY: To compare the neuromusculoskeletal characteristics of
      those with writers' cramp (WC) and musicians' cramp (MC), and evaluate
      responsiveness to learning-based sensorimotor training. METHODS: Twenty-seven
      individuals (14 musicians, 13 writers) participated in 8 weeks of supervised
      therapy supplemented with a home program. Between-group differences on measures
      of musculoskeletal (physical), sensory, and motor performance were evaluated at
      baseline and post-intervention. RESULTS: Subjects with MC had a higher level of
      functional independence and better range of motion, but less strength in the
      affected upper limb than those of subjects with WC. Subjects with MC demonstrated
      greater accuracy on graphesthesia, kinesthesia, and localization at baseline. No
      between-group differences in motor performance were noted at baseline or post
      intervention. Following individually adapted learning-based sensorimotor
      training, both groups improved in musculoskeletal (physical) parameters, sensory
      processing, and motor control; however, improvements on certain subtests differed
      by group. At follow-up, differences in posture, ROM, strength, graphesthesia, and
      kinesthesia persisted between the groups. CONCLUSIONS: Subjects with WC have
      different physical and performance risk factors compared with those of subjects
      with MC. Intervention paradigms are efficacious, but variable responses to
      rehabilitation occur.

PMID- 19389605
TI  - Understanding the mechanisms by which probiotics inhibit gastrointestinal
      pathogens.
AB  - In recent years, there has been a growing interest in the use of probiotic
      bacteria for the maintenance of general gastrointestinal health and the
      prevention or treatment of intestinal infections. Whilst probiotics are
      documented to reduce or prevent specific infectious diseases of the GI tract, the
      mechanistic basis of this effect remains unclear. It is likely that diverse modes
      of-action contribute to inhibition of pathogens in the gut environment and
      proposed mechanisms include (i) direct antimicrobial activity through production
      of bacteriocins or inhibitors of virulence gene expression; (ii) competitive
      exclusion by competition for binding sites or stimulation of epithelial barrier
      function; (iii) stimulation of immune responses via increases of sIgA and anti
      inflammatory cytokines and regulation of proinflammatory cytokines; and (iv)
      inhibition of virulence gene or protein expression in gastrointestinal pathogens.
      In this review, we discuss the modes of action by which probiotic bacteria may
      reduce gastrointestinal infections, and highlight some recent research which
      demonstrates the mechanistic basis of probiotic cause and effect.

PMID- 19389606
TI  - Sensory impacts of food-packaging interactions.
AB  - Sensory changes in food products result from intentional or unintentional
      interactions with packaging materials and from failure of materials to protect
      product integrity or quality. Resolving sensory issues related to plastic food
      packaging involves knowledge provided by sensory scientists, materials
      scientists, packaging manufacturers, food processors, and consumers. Effective
      communication among scientists and engineers from different disciplines and
      industries can help scientists understand package-product interactions. Very
      limited published literature describes sensory perceptions associated with food
      package interactions. This article discusses sensory impacts, with emphasis on
      oxidation reactions, associated with the interaction of food and materials,
      including taints, scalping, changes in food quality as a function of packaging,
      and examples of material innovations for smart packaging that can improve sensory
      quality of foods and beverages. Sensory evaluation is an important tool for
      improved package selection and development of new materials.

PMID- 19389607
TI  - Developmental trajectories in food allergy: a review.
AB  - Increasing recognition of the importance of the relationships between
      perceptions, emotions, behaviors and health has changed the way health and
      disease are portrayed and researched. A chronic condition may affect and/or
      interact with already existing normative demands and changes in socialization.
      Although the prevalence of food allergy and anaphylaxis have been reportedly
      increasing, the emotional and social impact of growing up with food allergy has
      received little emphasis. In this paper, we present current findings on the
      biopsychosocial impact of food allergy on children in order to gain insight into
      the food allergy experience, from the perspective of the child, teen, and parent
      living with food allergy, with particular attention to developmental aspects. Due
      to the scarcity of publications on the psychosocial dimensions of food allergy,
      we also draw on selected literature on children's and parent's experience of, and
      coping with chronic disease that may inform research into food allergy. To this
      end, we review some general developmental mechanisms that may underpin and
      explain normative age-graded shifts in patterns of coping across childhood and
      adolescence. We also highlight gaps in the literature and assess implications of
      current research in food allergy and other chronic diseases for intervention and
      prevention of negative short and long term outcomes.

PMID- 19389608
TI  - Maple syrup-production, composition, chemistry, and sensory characteristics.
AB  - Maple syrup is made from sap exuded from stems of the genus Acer during the
      springtime. Sap is a dilute solution of primarily water and sucrose, with varying
      amounts of amino and organic acids and phenolic substances. When concentrated,
      usually by heating, a series of complex reactions produce a wide variety of
      flavor compounds that vary due to processing and other management factors,
      seasonal changes in sap chemistry, and microbial contamination. Color also forms
      during thermal evaporation. Flavor and color together are the primary factors
      determining maple syrup grade, and syrup can range from very light-colored and
      delicate-flavored to very dark-colored and strong-flavored.

PMID- 19389609
TI  - Maternal fumonisin exposure as a risk factor for neural tube defects.
AB  - Fumonisins are mycotoxins produced by the fungus F. verticillioides, a common
      contaminant of maize (corn) worldwide. Maternal consumption of fumonisin B(1)
      contaminated maize during early pregnancy has recently been associated with
      increased risk for neural tube defects (NTDs) in human populations that rely
      heavily on maize as a dietary staple. Experimental administration of purified
      fumonisin to mice early in gestation also results in an increased incidence of
      NTDs in exposed offspring. Fumonisin inhibits the enzyme ceramide synthase in de
      novo sphingolipid biosynthesis, resulting in an elevation of free sphingoid bases
      and depletion of downstream glycosphingolipids. Increased sphingoid base
      metabolites (i.e., sphinganine-1-phosphate) may perturb signaling cascades
      involved in embryonic morphogenesis by functioning as ligands for sphingosine-1-P
      (S1P) receptors, a family of G-protein-coupled receptors that regulate key
      biological processes such as cell survival/proliferation, differentiation and
      migration. Fumonisin-induced depletion of glycosphingolipids impairs expression
      and function of the GPI-anchored folate receptor (Folr1), which may also
      contribute to adverse pregnancy outcomes. NTDs appear to be multifactorial in
      origin, involving complex gene-nutrient-environment interactions. Vitamin
      supplements containing folic acid have been shown to reduce the occurrence of
      NTDs, and may help protect the developing fetus from environmental teratogens.
      Fumonisins appear to be an environmental risk factor for birth defects, although
      other aspects of maternal nutrition and genetics play interactive roles in
      determining pregnancy outcome. Minimizing exposures to mycotoxins through
      enhanced agricultural practices, identifying biomarkers of exposure,
      characterizing mechanisms of toxicity, and improving maternal nutrition are all
      important strategies for reducing the NTD burden in susceptible human
      populations.

PMID- 19389611
TI  - There was a time when fatigue was not considered to be an intrinsic part of any
      disease. Foreword.

PMID- 19389610
TI  - Mechanistic and pharmacological analyses of HIV-1 integration.
AB  - Significant advances have transpired in the human immunodeficiency virus type 1
      (HIV-1) integration field in recent years. Considering its essential nature,
      integrase has long been a target of interest for antiviral drug development. The
      most significant advance was the approval of the Merck compound raltegravir, the
      first licensed integrase inhibitor, in October 2007. Another milestone was the
      identification and characterization of specific nucleoprotein complexes that
      mediate integrase 3' processing and DNA strand transfer activities in vitro.
      Genome-wide distribution analyses have furthermore revealed that different
      retroviruses differentially target distinctive regions of chromatin during
      integration. For examples, lentiviruses favor actively transcribed genes whereas
      gammaretroviruses such as Moloney murine leukemia virus prefer transcriptional
      start sites. Though the underlying mechanisms are unknown for most retroviruses,
      the lentiviral preference is in large part guided through the interaction with
      the integrase binding protein lens epithelium-derived growth factor (LEDGF)/p75.
      Experimental methods that formed the foundations for each of these advances, as
      well as other techniques topical to the study of HIV-1 integration, are described
      in this issue of Methods.

PMID- 19389612
TI  - Medical literature generally defines fatigue as an overwhelming sense of
      tiredness. Preface.

PMID- 19389613
TI  - Assessment of fatigue in adults with disabilities.
AB  - Fatigue is prevalent and can produce major public health consequences. Assessment
      of fatigue by the PM&R physician begins with a careful history and physical
      examination, complemented by pertinent rating scales and laboratory studies. In
      adults with disabilities, a wide variety of etiologies may lead to fatigue.
      Educating and providing resources about fatigue to patients can help open the
      discussion about this highly debilitating symptom.

PMID- 19389614
TI  - Functional neuroimaging of fatigue.
AB  - Clearly, the use of functional neuroimaging for the study of fatigue is in its
      infancy. Relatively few studies focusing on fatigue using functional neuroimaging
      techniques have been published, and the few that exist focus primarily on persons
      with MS and CFS. The vast majority of these studies have examined self-reported
      fatigue, an approach that benefits from ease of administration but suffers from
      significant difficulties in interpretation. For example, we know that self
      reported fatigue most often correlates with the degree of psychopathology.1 We
      also know that with more than 100 years of inquiry, self-reported fatigue does
      not correlate with objective measures of fatigue. As such, when functional
      imaging studies show a relationship between self-reported fatigue and activities
      in distinct areas of the brain, one must remain cautious about the interpretation
      of these results. A more recent approach in the functional imaging literature is
      to assess fatigue behaviorally during scanning and relate such objective measures
      of fatigue with cerebral activation. Although this is a new and novel approach,
      it remains unclear if this approach of operationally defining fatigue
      behaviorally will be a more valid paradigm in understanding the elusive construct
      of fatigue. Although fatigue is extraordinarily common as a symptom in many
      neurologic and psychiatric diseases, little is known about its precise mechanism.
      Chaudhuri and Behan hypothesized that the nonmotor functions of the basal ganglia
      play a key role in central fatigue. Specifically, they posit that fatigue is due
      to "alterations in the normal flow of sequential activation within the basal
      ganglia system affecting the neural integrator and the cortical feedback by the
      associated loop of the striato-thalamo-cortical fibers is a possible mechanism of
      central fatigue ." (p40). Therefore, other regions interacting with the basal
      ganglia may also contribute to fatigue, including the frontal cortex, thalamus,
      and the amygdala. In general, the functional imaging studies reviewed in this
      article tend to generally support the suggestion that damage to cortical
      subcortical circuitry might be to blame for fatigue as well. If indeed fatigue is
      associated with functional impairment in a cortical-subcortical circuitry, it
      might be that studies that have examined structural damage (eg, total lesion load
      throughout the brain) may simply not provide the sensitivity required to detect a
      relationship between fatigue and pathology. After more than 100 years of
      frustration, it appears that functional neuroimaging techniques promise to
      provide an exciting potential for significant advances in our elusive
      understanding of the brain mechanisms associated with fatigue in clinical
      populations.

PMID- 19389615
TI  - Fatigue in children with neurologic impairments.
AB  - Children with neuromuscular illness are at high risk for fatigue. This symptom,
      although difficult to decipher, can contribute significantly to the child's
      disability. It is, therefore, imperative to consider fatigue in the management of
      children with special health care needs. Currently, the literature on chronic
      fatigue in children is sparse and so more investigative work must be done to
      understand and manage this condition.

PMID- 19389616
TI  - Fatigue in Parkinson disease, stroke, and traumatic brain injury.
AB  - Fatigue is a serious, QoL-limiting symptom of many neurologic conditions.
      Physicians should be thorough and consistent in their assessment for this problem
      and not let motor symptoms monopolize an office visit. Although the use of
      pharmacology to treat this problem has predominantly only anecdotal evidence of
      efficacy, several nonpharmacologic interventions may prove helpful. The
      directions of future research should aim to create clear treatment guidelines
      using the pharmacologic agents available.

PMID- 19389617
TI  - Fatigue in multiple sclerosis.
AB  - In summary, MS-related fatigue can be a severe problem causing interference with
      home and vocational activities. There are multiple factors that can contribute to
      fatigue in MS, and it is important for the patient, family, and clinician to be
      aware of potential confounders that may worsen fatigue. Clearer understanding
      about the etiology of fatigue is necessary. Additional larger, randomized,
      clinical trials are needed to evaluate etiology, pathophysiology, and both
      pharmacologic and nonpharmacologic interventions. Given the varying nature of
      fatigue and the limited evidence that fatigue in MS patients is highly dependent
      on self-perceived scores, additional research into the effect of psychosocial and
      psychological interventions is recommended. A multidisciplinary approach to
      fatigue is encouraged when treatments are considered for maximum benefit.

PMID- 19389618
TI  - Fatigue in rheumatologic diseases.
AB  - Today, fatigue still remains an under-reported symptom in rheumatologic diseases,
      infrequently addressed by patient and physician. Although not all of the causes
      of fatigue in rheumatologic diseases have been fully elucidated, recognizing the
      multifactorial components is essential in formulating targeted, effective
      treatment strategies. Deconstructing rheumatologic diseases into discrete
      symptoms such as fatigue in an effort to identify specific causes and formulate
      targeted treatments remains a daunting task. High-quality RCTs will be required
      to evaluate the effectiveness of combined pharmacologic and nonpharmacologic
      strategies, which empirically appear to be the most promising. To date, this
      research is lacking.

PMID- 19389619
TI  - Fatigue in cardiopulmonary disease.
AB  - Fatigue is often the major presenting complaint in patients with cardiac or
      pulmonary disease. This review explores a number of the multiple possible causes
      of fatigue in this population of patients. The identification of fatigue and
      possible approaches to the treatment of fatigue in cardiopulmonary patients are
      presented. Finally, the role of exercise and appropriate exercise prescription
      for treatment of fatigue for cardiac and pulmonary patients is discussed.

PMID- 19389620
TI  - Cancer-related fatigue.
AB  - CRF is indisputably a significant problem with important public health and
      medical economic implications. As the prevalence of cancer survivorship grows,
      the impact of CRF will increase. Physiatrists have not historically played an
      active role in caring for affected patients. In the author's opinion, this is
      unfortunate, since the holistic, integrated, and cross-disciplinary approach that
      characterizes physiatry seems ideally suited to offer patients meaningful
      benefit. Physiatrists with a clinical interest are likely to be robustly rewarded
      with interest from the oncological community, as CRF is a frustrating and
      devastating problem for patients and clinicians alike.

PMID- 19389621
TI  - Lean and mean: nanoparticle-based delivery improves performance of cancer drugs.

PMID- 19389622
TI  - Divergent pathways in the biosynthesis of bisindole natural products.
AB  - Two molecules of the amino acid L-tryptophan are the biosynthetic precursors to a
      class of natural products named the "bisindoles." Hundreds of these bisindole
      molecules have been isolated from natural sources, and many of these molecules
      have potent medicinal properties. Recent studies have clarified the biosynthetic
      construction of six bisindole molecules, revealing novel enzymatic mechanisms and
      leading to combinatorial synthesis of new bisindole compounds. Collectively,
      these results provide a vantage point for understanding how much of the diversity
      of the bisindole class is generated from a small number of diverging pathways
      from L-tryptophan, as well as enabling identification of bisindoles that are
      likely derived via completely distinct biosynthetic pathways.

PMID- 19389623
TI  - Docking motif-guided mapping of the interactome of protein phosphatase-1.
AB  - The ubiquitous protein Ser/Thr phosphatase-1 (PP1) interacts with dozens of
      regulatory proteins that are structurally unrelated. However, most of them share
      a short, degenerate "RVxF"-type docking motif. Using a broad in silico screening
      based on a stringent definition of the RVxF motif, in combination with a
      multistep biochemical validation procedure, we have identified 78 novel mammalian
      PP1 interactors. A global analysis of the validated RVxF-based PP1 interactome
      not only provided insights into the conserved features of the RVxF motif but also
      led to the discovery of additional common PP1 binding elements, described as the
      "SILK" and "MyPhoNE" motifs. In addition to the doubling of the known mammalian
      PP1 interactome, our data contribute to the design of PP1 interaction networks.
      Notably, an interaction network linking PP1 interactors discloses a pleiotropic
      role of PP1 in cell polarity.

PMID- 19389624
TI  - Gas-phase unfolding and disassembly reveals stability differences in ligand-bound
      multiprotein complexes.
AB  - Mass spectrometry (MS) is widely used to assess the binding of small molecules to
      proteins and their complexes. In many cases, subtle differences in the stability
      afforded by binding of ligands to protein assemblies cannot be detected by MS.
      Here we show that monitoring the unfolding of protein subunits, using ion
      mobility-MS, allows differentiation of the effects of ligand binding not normally
      observed by MS alone. Using wild-type and disease-associated variants of
      tetrameric transthyretin, MS data indicate that populations of the variant
      protein are less stable than wild-type. Ion mobility-MS, however, is able to show
      that the natural ligand of transthyretin, thyroxine, provides a larger stability
      increase to the tetramer composed of variant subunits than to the wild-type
      protein-ligand complex. Overall, therefore, our results have implications for
      small-molecule drug design directed at multiprotein targets.

PMID- 19389625
TI  - Aptamer-derived peptides as potent inhibitors of the oncogenic RhoGEF Tgat.
AB  - Guanine nucleotide exchange factors (GEFs) activate the Rho GTPases by
      accelerating their GDP/GTP exchange rate. Some RhoGEFs have been isolated based
      on their oncogenic potency, and strategies to inhibit their activity are
      therefore actively being sought. In this study we devise a peptide inhibitor
      screening strategy to target the GEF activity of Tgat, an oncogenic isoform of
      the RhoGEF Trio, based on random mutations of the Trio inhibitor TRIP alpha,
      which we previously isolated using a peptide aptamer screen. This identifies one
      peptide, TRIP(E32G), which specifically inhibits Tgat GEF activity in vitro and
      significantly reduces Tgat-induced RhoA activation and foci formation.
      Furthermore, subcutaneous injection of cells expressing Tgat and TRIP(E32G) into
      nude mice reduces the formation of Tgat-induced tumors. Our approach thus
      demonstrates that peptide aptamers are potent inhibitors that can be used to
      interfere with RhoGEF functions in vivo.

PMID- 19389626
TI  - Structure and function of the glycopeptide N-methyltransferase MtfA, a tool for
      the biosynthesis of modified glycopeptide antibiotics.
AB  - There is a considerable interest in the modification of existing antibiotics to
      generate new antimicrobials. Glycopeptide antibiotics (GPAs) are effective
      against serious Gram-positive bacterial pathogens including methicillin-resistant
      Staphylococcus aureus. However, resistance to these antibiotics is becoming a
      serious problem requiring new strategies. We show that the Amycolatopsis
      orientalis (S)-adenosyl-L-methionine-dependent methyltransferase MtfA, from the
      vancomycin-class GPA chloroeremomycin biosynthetic pathway, catalyzes in vivo and
      in vitro methyl transfer to generate methylated GPA derivatives of the
      teicoplanin class. The crystal structure of MtfA complexed with (S)-adenosyl-L
      methionine, (S)-adenosylhomocysteine, or sinefungin inhibitor, coupled with
      mutagenesis, identified His228 as a likely general base required for methyl
      transfer to the N terminus of the glycopeptide. Computational docking and
      molecular dynamics simulations were used to model binding of demethyl-vancomycin
      aglycone to MtfA. These results demonstrate its utility as a tool for engineering
      methylated analogs of GPAs.

PMID- 19389627
TI  - Discovery and characterization of a highly selective FAAH inhibitor that reduces
      inflammatory pain.
AB  - Endocannabinoids are lipid signaling molecules that regulate a wide range of
      mammalian behaviors, including pain, inflammation, and cognitive/emotional state.
      The endocannabinoid anandamide is principally degraded by the integral membrane
      enzyme fatty acid amide hydrolase (FAAH), and there is currently much interest in
      developing FAAH inhibitors to augment endocannabinoid signaling in vivo. Here, we
      report the discovery and detailed characterization of a highly efficacious and
      selective FAAH inhibitor, PF-3845. Mechanistic and structural studies confirm
      that PF-3845 is a covalent inhibitor that carbamylates FAAH's serine nucleophile.
      PF-3845 selectively inhibits FAAH in vivo, as determined by activity-based
      protein profiling; raises brain anandamide levels for up to 24 hr; and produces
      significant cannabinoid receptor-dependent reductions in inflammatory pain. These
      data thus designate PF-3845 as a valuable pharmacological tool for in vivo
      characterization of the endocannabinoid system.

PMID- 19389628
TI  - An iterative nonribosomal peptide synthetase assembles the pyrrole-amide
      antibiotic congocidine in Streptomyces ambofaciens.
AB  - Congocidine (netropsin) is a pyrrole-amide (oligopyrrole, oligopeptide)
      antibiotic produced by Streptomyces ambofaciens. We have identified, in the right
      terminal region of the S. ambofaciens chromosome, the gene cluster that directs
      congocidine biosynthesis. Heterologous expression of the cluster and in-frame
      deletions of 8 of the 22 genes confirm the involvement of this cluster in
      congocidine biosynthesis. Nine genes can be assigned specific functions in
      regulation, resistance, or congocidine assembly. In contrast, the biosynthetic
      origin of the precursors cannot be easily inferred from in silico analyses.
      Congocidine is assembled by a nonribosomal peptide synthetase (NRPS) constituted
      of a free-standing module and several single-domain proteins encoded by four
      genes. The iterative use of its unique adenylation domain, the utilization of
      guanidinoacetyl-CoA as a substrate by a condensation domain, and the control of 4
      aminopyrrole-2-carboxylate polymerization constitute the most original features
      of this NRPS.

PMID- 19389629
TI  - Combination of reverse and chemical genetic screens reveals angiogenesis
      inhibitors and targets.
AB  - We combined reverse and chemical genetics to identify targets and compounds
      modulating blood vessel development. Through transcript profiling in mice, we
      identified 150 potentially druggable microvessel-enriched gene products.
      Orthologs of 50 of these were knocked down in a reverse genetic screen in
      zebrafish, demonstrating that 16 were necessary for developmental angiogenesis.
      In parallel, 1280 pharmacologically active compounds were screened in a human
      cell-based assay, identifying 28 compounds selectively inhibiting endothelial
      sprouting. Several links were revealed between the results of the reverse and
      chemical genetic screens, including the serine/threonine (S/T) phosphatases
      ppp1ca, ppp1cc, and ppp4c and an inhibitor of this gene family; Endothall. Our
      results suggest that the combination of reverse and chemical genetic screens, in
      vertebrates, is an efficient strategy for the identification of drug targets and
      compounds that modulate complex biological systems, such as angiogenesis.

PMID- 19389630
TI  - An exosite-specific ssDNA aptamer inhibits the anticoagulant functions of
      activated protein C and enhances inhibition by protein C inhibitor.
AB  - Activated protein C (APC) is a serine protease with anticoagulant, anti
      inflammatory, and cytoprotective properties. Using recombinant APC, we identified
      a class of single-stranded DNA aptamers (HS02) that selectively bind to APC with
      high affinity. Interaction of HS02 with APC modulates the protease activity in a
      way such that the anticoagulant functions of APC are inhibited and its reactivity
      toward the protein C inhibitor is augmented in a glysoaminoglycan-like fashion,
      whereas APC's antiapoptotic and cytoprotective functions remain unaffected. Based
      on these data, the binding site of HS02 was localized to the basic exosite of
      APC. These characteristics render the exosite-specific aptamers a promising tool
      for the development of APC assays and a potential therapeutic agent applicable
      for the selective control of APC's anticoagulant activity.

PMID- 19389631
TI  - Differential presentation of protein interaction surfaces on the androgen
      receptor defines the pharmacological actions of bound ligands.
AB  - The pharmacological activity of different nuclear receptor ligands is reflected
      by their impact on receptor structure. Thus, we asked whether differential
      presentation of protein-protein interaction surfaces on the androgen receptor
      (AR), a surrogate assay of receptor conformation, could be used in a prospective
      manner to define the pharmacological activity of bound ligands. To this end, we
      identified over 150 proteins/polypeptides whose ability to interact with AR is
      influenced in a differential manner by ligand binding. The most discriminatory of
      these protein-AR interactions were used to develop a robust compound-profiling
      tool that enabled the separation of ligands into functionally distinguishable
      classes. Importantly, the ligands within each class exhibited similar
      pharmacological activities, a result that highlights the relationship between
      receptor structure and activity and provides direction for the discovery of novel
      AR modulators.

PMID- 19389633
TI  - Endovascular treatment of peripheral artery disease (PAD): so old yet so far from
      evidence!

PMID- 19389632
TI  - A soluble sulfogalactosyl ceramide mimic promotes Delta F508 CFTR escape from
      endoplasmic reticulum associated degradation.
AB  - AdaSGC binds Hsc70s to inhibit ATPase activity. Using single-turnover assays,
      adaSGC, a soluble SGC mimic, preferentially inhibited Hsp40-activated Hsc70 ATP
      hydrolysis (Ki approximately 10 microM) to reduce C-terminal Hsc70-peptide
      binding and, potentially, chaperone function. ERAD of misfolded Delta F508 CFTR
      requires Hsc70-Hsp40 chaperones. In transfected baby hamster kidney (BHK) cells,
      adaSGC increased Delta F508CFTR ERAD escape, and after low-temperature glycerol
      rescue, maturation, and iodide efflux. Inhibition of SGC biosynthesis reduced
      Delta F508CFTR but not wtCFTR expression, whereas depletion of other
      glycosphingolipids had no affect. WtCFTR transfected BHK cells showed increased
      SGC synthesis compared with Delta F508CFTR/mock-transfected cells. Partial rescue
      of Delta F508CFTR by low-temperature glycerol increased SGC synthesis. AdaSGC
      also increased cellular endogenous SGC levels. SGC in the lung, liver, and kidney
      was severely depleted in Delta F508CFTR compared with wtCFTR mice, suggesting a
      role for CFTR in SGC biosynthesis.

PMID- 19389634
TI  - Neurological examination of the cat. How to get started.
AB  - PRACTICAL RELEVANCE: Neurological diagnosis in veterinary practice can be very
      challenging, especially as many animals with neurological signs present as
      emergencies. Nevertheless, even in the absence of specialist facilities for
      definitively diagnosing neurological disorders, a great deal of information can
      be gained with some basic knowledge and a logical stepwise approach. CLINICAL
      CHALLENGES: A lack of initial consideration as to where exactly the problem might
      be localised within the nervous system, and what kind of disease processes may be
      in operation there, is the most common cause of failure in the diagnosis of
      neurological conditions in cats. Too often, this presents a hurdle that pushes
      the clinician into neglecting the neurological evaluation in favour of making the
      best guess at which diagnostic tests may achieve a diagnosis. AUDIENCE: This
      article is aimed at all first opinion practitioners who see cats as, undoubtedly,
      whatever the presentation, the approach to a suspected neurological case can be
      daunting for even the calmest and most patient clinician. It will provide the
      necessary tools to perform and make the most of the neurological examination of
      the feline patient.

PMID- 19389635
TI  - The wobbly cat. Diagnostic and therapeutic approach to generalised ataxia.
AB  - PRACTICAL RELEVANCE: Generalised ataxia is one of the most common neurological
      presentations identified in cats in practice. The causes can be subdivided into
      three forms on the basis of the neuroanatomical diagnosis: cerebellar, vestibular
      and sensory (spinal or general proprioceptive) ataxia. The type of ataxia will
      determine the diagnostic procedures and select the differential diagnoses, and an
      accurate neuroanatomical diagnosis is therefore essential. The differential
      diagnosis list can then be further tailored on the basis of patient signalment,
      clinical presentation and progression. GLOBAL IMPORTANCE: Irrespective of the
      world region, most of the causes of generalised ataxia in the cat are similar and
      many have been identified for a number of years (cerebellar hypoplasia has been
      recognised since the late 19th century). However, it is the advent of new
      technology, in particular veterinary access to magnetic resonance imaging, which
      has resulted in particularly rapid advances in our understanding, investigation
      and management of these different forms of ataxia. AUDIENCE: This article
      introduces the classification of patients with ataxia on the basis of their
      clinical presentation, discusses the common differential diagnoses associated
      with each form, and briefly reviews the more important diseases from a clinical
      perspective. It is aimed at all veterinarians who treat cats.

PMID- 19389636
TI  - The paralyzed cat. Neuroanatomic diagnosis and specific spinal cord diseases.
AB  - PRACTICAL RELEVANCE: Although gait disturbance is one of the most common
      neurological presentations in feline medicine, the clinical approach to the
      paralyzed cat can be challenging. After excluding orthopedic and cardiovascular
      diseases that may mimic a neurological condition, the clinician has to address a
      long list of different diseases that may affect the spinal cord and produce
      paresis. CLINICAL CHALLENGES: In many cases a definitive cause of spinal weakness
      in cats is difficult to prove. Even when treatable diseases are identified, the
      prognosis is very much dependent on the severity of the clinical signs and their
      chronicity. This review sets out to describe the specific approach, diagnosis and
      management of cats with spinal cord disease and to outline the most common
      diseases responsible. PATIENT GROUP: Patients of either gender and all ages and
      breeds can be affected by spinal cord disease. EVIDENCE BASE: Many diseases
      affecting the spinal cord of cats, which include fibrocartilaginous embolic
      myelopathy, intervertebral disc disease, exogenous spinal cord trauma, spinal
      cord lymphosarcoma and feline infectious peritonitis, are well described in the
      literature. Many of these descriptions, however, have been based on case reports
      or series. While there have been several retrospective studies that describe the
      characteristics and incidence of these diseases in cats, there are no long term
      treatment trials or outcome studies to assist with prognostic determinations.

PMID- 19389637
TI  - The weak cat. Practical approach and common neurological differentials.
AB  - PRACTICAL RELEVANCE: Weakness is recognized somewhat infrequently in cats, but is
      an important manifestation of neurological disease. The clinician must perform a
      complete neurological examination to determine the neuroanatomic basis for the
      weakness. As for all species, the neuroanatomic diagnosis allows the clinician to
      generate an appropriate differential diagnosis, to design a diagnostic plan, to
      prognosticate, and ultimately to develop a treatment plan. CLINICAL CHALLENGES:
      The cause(s) of neurological weakness in the cat may be difficult to determine
      without access to advanced imaging modalities, cerebrospinal fluid analysis or
      electrodiagnostics. However, an accurate neuroanatomic diagnosis allows the
      clinician to pursue preliminary anomalous (vertebral anomalies), metabolic (eg,
      diabetes mellitus, electrolyte abnormalities) and neoplastic differentials via
      blood work, vertebral column and thoracic radiography, and abdominal ultrasound.
      Subsequently, referral to a specialty veterinary hospital may be warranted to
      pursue advanced neurodiagnostics. AUDIENCE: This review provides a framework for
      generating a neuroanatomic and differential diagnosis in the weak cat. It also
      discusses the pathogenesis and clinical signs associated with the most common
      neurological differentials for feline paresis. As such, it is aimed at both
      primary health care and specialty veterinarians. PATIENT GROUP: The neurological
      conditions discussed in this review cause weakness in cats of all age groups.

PMID- 19389638
TI  - The seizuring cat. Diagnostic work-up and therapy.
AB  - PRACTICAL RELEVANCE: Although seizures occur less commonly in cats compared with
      dogs, they are one of the most common forms of neurological disease in the feline
      patient. Cats may experience both focal (partial) and generalized seizures and
      causes are divided into primary disorders, in which there is no underlying cause
      (ie, idiopathic epilepsy), and secondary disorders. Cats with secondary seizure
      disorders have either an underlying structural lesion or metabolic disease.
      PATIENT GROUP: Seizures affect cats of all ages. Cats with idiopathic epilepsy
      tend to be younger (approximately 3.5 years) than cats with secondary seizure
      disorders (approximately 8 years). AUDIENCE: This review of feline seizures is
      directed at all veterinarians who treat cats, both in an emergency setting as
      well as in general practice. CLINICAL CHALLENGES: Refractory seizures are often a
      diagnostic and therapeutic challenge. A systematic approach to the seizuring cat
      is described, easing the task of diagnosing the cause of the seizures. In
      addition, novel antiepileptics are discussed, which can be used as add-on drugs
      in challenging feline seizure cases. EVIDENCE BASE: Compared with the canine
      counterpart, the literature regarding treatment of feline seizures is less
      established. Recent clinical trials and studies are focusing on new treatment
      options for feline seizures. Specifically, these studies, some of which are
      ongoing, have led to the use of levetiracetam, zonisamide and pregabalin as add
      on antiepileptics in cases that are refractory to phenobarbital.

PMID- 19389639
TI  - The cat with neurological manifestations of systemic disease. Key conditions
      impacting on the CNS.
AB  - PRACTICAL RELEVANCE: A number of systemic diseases are associated with
      neurological deficits. Most systemic diseases that impact on the nervous system
      result in multifocal neurological signs; however, isolated deficits can also be
      observed. This article reviews the clinical signs, pathophysiology, diagnosis,
      treatment and prognosis of four important systemic diseases with neurological
      consequences: feline infectious peritonitis, toxoplasmosis, hypertension and
      hepatic encephalopathy. CLINICAL CHALLENGES: Early recognition of systemic signs
      of illness in conjunction with neurological deficits will allow for prompt
      diagnosis and treatment. While neurological examination of the feline patient can
      undoubtedly be challenging, hopefully the accompanying articles in this special
      issue will enable the clinician to approach these cases with more confidence.
      EVIDENCE BASE: The veterinary literature contains numerous reports detailing the
      impact of systemic disease on the nervous system. Unfortunately, very few
      references provide detailed descriptions of large cohorts of affected cats. This
      review summarises the literature underpinning the four key diseases under
      discussion.

PMID- 19389640
TI  - Pleural empyema secondary to amebic liver abscess.

PMID- 19389641
TI  - Severe genital human papillomavirus infection in a sexually abused child.

PMID- 19389642
TI  - Disseminated cryptococcosis in an HIV-negative patient.

PMID- 19389643
TI  - Relationship between the spectral characteristics of atrial fibrillation and
      atrial tachycardias that occur after catheter ablation of atrial fibrillation.

PMID- 19389645
TI  - Role of the right atrial substrate in different types of atrial arrhythmias.
AB  - BACKGROUND: The regional distribution of the low-voltage zones (LVZs) may relate
      to the maintenance of atrial arrhythmias in the right atrium (RA). OBJECTIVES:
      The purpose of this study was to investigate the RA substrate characteristics in
      different types of atrial arrhythmias originating from RA and left atrium (LA).
      METHODS: Forty-five patients (35 men, age = 62 +/- 15 years) with RA atypical
      atrial flutter (n = 15, group 1), RA atrial fibrillation (AF; n = 15, no PV
      initiating foci, group 2), and LA AF (n = 1 5, no RA arrhythmias, group 3)
      referred for three-dimensional EnSite mapping were included. Voltage and
      activation maps were visualized. RESULTS: The mean voltage of the RA was lower in
      group 2, and compared with group 3, a voltage reduction during atrial pacing was
      evident in groups 1 and 2. The fixed LVZs (independent of the rhythm) were mostly
      located along the lower crista terminalis (CT). A functional extension of the LVZ
      was located on the CT in 84% of patients, sinus venosa in 18%, and free-wall
      region in 27%, forming the borders of the slow conduction isthmus for the
      reentrant circuits. The number of slow conduction isthmuses was 1.3 +/- 0.9, 2.2
      +/- 1.0, and 0.87 +/- 0.74, for the groups 1-3 patients, respectively (P <.05).
      Radiofrequency ablation connecting the LVZs successfully eliminated those
      isthmuses. The long-term follow-up revealed that 66% of the patients remained in
      sinus rhythm. CONCLUSIONS: Single and multiple slow conduction isthmuses bordered
      by the fixed and functional LVZs were critical for the reentrant circuits in the
      RA. The conduction isthmuses could be identified by their substrate
      characteristics and ablated successfully.

PMID- 19389646
TI  - Searching for triggers of sudden death in hypertrophic cardiomyopathy: chasing
      after the wind?

PMID- 19389647
TI  - The Sprint Fidelis story: where are we now?

PMID- 19389648
TI  - Increased rate of subacute lead complications with small-caliber implantable
      cardioverter-defibrillator leads.
AB  - BACKGROUND: Increased rates of complications related to the use of small-diameter
      implantable cardioverter-defibrillator (ICD) leads have been reported. Lead
      design and engineering aimed at reducing ICD lead diameter may increase
      associated subacute complications, including cardiac perforation, lead
      dislodgement, or lead failure. OBJECTIVE: The purpose of this study was to
      determine whether lead caliber altered the risk of perforation, lead
      dislodgement, or lead failure in a single center. METHODS: All patients with
      right ventricular (RV) ICD lead implantation at Vanderbilt University and VA
      Nashville Medical Center between January 1, 2007, and August 31, 2007, were
      included in this study. Leads implanted during this period were the Riata 1580,
      Riata ST 7000 (St. Jude Medical, St. Paul, MN), Sprint Fidelis 6949, and Sprint
      Quattro 6947 (Medtronic, Minneapolis, MN). Information was collected
      retrospectively. RESULTS: A total of 305 ICD leads were implanted (138 small
      diameter, 167 standard diameter) during the study period. Failure was defined as
      development of high pacing threshold, marked sensing change, cardiac perforation,
      or development of extracardiac stimulation. A total of 11 lead failures occurred
      in the small-diameter lead group, versus one in the standard group. Implantation
      of a small-diameter lead (Riata 1580, Riata ST 7000, or Sprint Fidelis 6949) was
      associated with a significant increase in failure rate, 8.0% versus 0.6% (P =
      .0008) compared with standard-size leads (Sprint Quattro 6947). CONCLUSIONS:
      Subacute lead-related complications were more likely with use of small-diameter
      ICD leads (Riata 1580, Riata ST 7000, Sprint Fidelis 6949) than with with
      standard-caliber ICD leads (Sprint Quattro 6947).

PMID- 19389649
TI  - Significance of QRS prolongation during diagnostic ajmaline test in patients with
      suspected Brugada syndrome.
AB  - BACKGROUND: Current consensus documents on Brugada syndrome recommend the
      diagnostic intravenous administration of a Na-channel blocker to be stopped when
      the QRS prolongs to > or =130% of baseline, presumably because of increased
      arrhythmic risk. OBJECTIVE: This study sought to assess QRS prolongation during
      ajmaline testing and its relation to arrhythmic risk. METHODS: We analyzed an
      electrocardiographic (ECG) database collected during ajmaline testing in 148
      patients (92 men, age 36 +/- 15 years). The QRS was measured at baseline and
      during the 1st to 7th, 10th, and 15th minute after the beginning of ajmaline
      administration. RESULTS: The average QRS prolongation was 36% +/- 16% (range 9%
      to 88%), not significantly different between positive (n = 30) and negative (n =
      118) tests. QRS prolonged to > or =130% during 16 (55%) positive and 71 (61%)
      negative tests (P = .50), with no clinical side effects. The incidence of
      ventricular arrhythmias was not significantly different between patients with and
      without QRS prolongation. Short runs (3 to 8 complexes) of nonsustained
      ventricular tachycardia occurred in 3 patients with QRS prolongation > or =130%.
      In 40% of positive tests, prolongation > or =130% occurred earlier by >1 minute
      than diagnostic Brugada ECG changes, i.e., early termination of the test could
      possibly have resulted in false-negative outcomes. CONCLUSION: QRS prolongation >
      or =130% occurs in >50% of all tests. In 40% of positive tests it occurs before
      diagnostic ECG changes. Always terminating the test when QRS prolongs > or =130%
      could possibly result in loss of important diagnostic information. It is
      appropriate to adjust the criteria for early termination of the test to the
      baseline QRS and possibly other factors.

PMID- 19389650
TI  - Ajmaline challenge: to stop or not to stop...

PMID- 19389651
TI  - Genome-wide association study of electrocardiographic conduction measures in an
      isolated founder population: Kosrae.
AB  - BACKGROUND: Cardiac conduction, as assessed by electrocardiographic PR interval
      and QRS duration, is an important electrophysiological trait and a determinant of
      arrhythmia risk. OBJECTIVE: We sought to identify common genetic determinants of
      these measures. METHODS: We examined 1604 individuals from the island of Kosrae,
      Federated States of Micronesia, an isolated founder population. We adjusted for
      covariates and estimated the heritability of quantitative electrocardiographic
      QRS duration and PR interval and, secondarily, its subcomponents, P-wave duration
      and PR segment. Finally, we performed a genome-wide association study (GWAS) in a
      subset of 1262 individuals genotyped using the Affymetrix GeneChip Human Mapping
      500K microarray. RESULTS: The heritability of PR interval was 34% (standard error
      [SE] 5%, P = 4 x 10(-18)); of PR segment, 31% (SE 6%, P = 3.2 x 10(-13)); and of
      P-wave duration, 17% (SE 5%, P = 5.8 x 10(-6)), but the heritablility of QRS
      duration was only 3% (SE 4%, P = .20). Hence, GWAS was performed only for the PR
      interval and its subcomponents. A total of 338,049 single nucleotide
      polymorphisms (SNPs) passed quality filters. For the PR interval, the most
      significantly associated SNPs were located in and downstream of the alpha-subunit
      of the cardiac voltage-gated sodium channel gene SCN5A, with a 4.8 ms (SE 1.0) or
      0.23 standard deviation increase in adjusted PR interval for each minor allele
      copy of rs7638909 (P = 1.6 x 10(-6), minor allele frequency 0.40). These SNPs
      were also associated with P-wave duration (P = 1.5 x 10(-4)) and PR segment (P =
      .01) but not with QRS duration (P > or =.22). CONCLUSIONS: The PR interval and
      its subcomponents showed substantial heritability in a South Pacific islander
      population and were associated with common genetic variation in SCN5A.

PMID- 19389652
TI  - The heritable nature of the electrocardiogram: How far can population genetics
      go?

PMID- 19389653
TI  - Infarct architecture and characteristics on delayed enhanced magnetic resonance
      imaging and electroanatomic mapping in patients with postinfarction ventricular
      arrhythmia.
AB  - BACKGROUND: Delayed enhanced magnetic resonance imaging (DE-MRI) can be used for
      the exact assessment of myocardial infarct scar. Electroanatomic (EA) mapping can
      identify the subendocardial extension of infarcts and is used to identify and
      eliminate areas critical for postinfarction ventricular arrhythmias. OBJECTIVES:
      The purpose of this study was to correlate DE-MRI with EA mapping in
      postinfarction patients with ventricular arrhythmias to assess myocardial infarct
      architecture and its relationship to postinfarction ventricular arrhythmias.
      METHODS: EA mapping during sinus rhythm was performed in 14 postinfarction
      patients (10 men; age 64 +/- 10 years; ejection fraction 0.33 +/- 0.12) referred
      for ablation of ventricular arrhythmias. All patients underwent prior DE-MRI.
      Both DE-MRI and EA mapping data were registered in three-dimensional space.
      Presence of scar and its transmurality as well as scar core versus gray zone were
      assessed on DE-MRI and correlated with EA maps; furthermore, the electrogram
      characteristics of the EA map were correlated with the DE-MRI. RESULTS: Scar
      areas as assessed by bipolar and unipolar voltages in the EA map both correlated
      well with the scar as defined by DE-MRI. The best cutoff value to differentiate
      subendocardial scar from normal myocardium was 1.0 mV for bipolar voltage and 5.8
      mV for unipolar voltage. Areas with DE had distinct electrophysiologic
      characteristics compared with nonenhancing sites. All identified sites that were
      critical for postinfarction ventricular tachycardia (31/31) and premature
      ventricular complexes (5/5) were located within areas of DE, with most (71%)
      being located in the core area of the scar. CONCLUSIONS: DE-MRI can accurately
      predict the EA characteristics of corresponding subendocardial locations.
      Critical sites of postinfarction arrhythmias were confined to areas of DE. The
      scar information on MRI can be selectively imported into an EA mapping system to
      facilitate the mapping and ablation procedure.

PMID- 19389654
TI  - The specialized rings and the endless saga of the AV node puzzle.

PMID- 19389655
TI  - Sympathetic nerve stimulation produces spatial heterogeneities of action
      potential restitution.
AB  - BACKGROUND: Restitution kinetics (RK) of action potential duration (APD) are
      classically studied by applying an extra impulse at varying diastolic intervals
      (DI) and might differ from RK elicited by sympathetic nerve stimulation (SNRK).
      OBJECTIVE: To measure 'Physiological' RK during gradual increases in heart rate
      caused by sympathetic nerve stimulation (SNS) and its possible spatial
      heterogeneities caused by non-uniform innervation of the myocardium. METHODS: The
      SNRK was measured from rabbit hearts with intact sympathetic innervation using
      optical mapping. APD versus DI were plotted from left ventricles during SNS, then
      with pacing using identical activation interval (AI) sequences. RESULTS: AI
      decreased (444 +/- 18 ms to 284 +/- 9 ms) in 25 s and recovered to baseline on
      SNS suspension (n = 10). APD versus DI plots were identical for SNS and pacing
      except that when maximum heart rate was reached, SNS elicited a further APD
      shortening compared with pacing. During SNS, APDs decreased from 216 +/- 9 ms to
      154 +/- 7 ms (29% +/- 2%) at the base and from 206 +/- 12 ms to 158 +/- 7 ms (20%
      +/- 2%) at the apex. During pacing, APDs at the base decreased from 216 +/- 9 ms
      to 170 +/- 7 ms (21% +/- 1%, SNS versus pacing: P < .05). In contrast, RK were
      similar at the apex for SNS and pacing. During SNS, the extra APD shortening at
      the base was associated with longer segments of RK curves with negative slopes
      and extra DI prolongation. Perfusion with the I(Ks) inhibitor HMR 1556 (0.5
      microM; n = 5) abolished differences in RK between SNS and pacing. Levels of
      KCNQ1 and tyrosine hydroxylase proteins were greater at the base than apex (n =
      4), implying that apex-base distributions for I(Ks) and sympathetic innervation
      are congruent with SNRK heterogeneities. CONCLUSION: The findings shed further
      insights on heterogeneities of sympathetic nerves, RK, and the role of I(Ks) in
      cardiac repolarization.

PMID- 19389656
TI  - The QT interval: too long, too short or just right.

PMID- 19389658
TI  - Inspirational surgical education: the way to a mature specialist identity.

PMID- 19389659
TI  - Inter-manual transfer and practice: coding of simple motor sequences.
AB  - Previous research suggests that movements are represented early in practice in
      visual-spatial coordinates/codes, which are effector independent, and later in
      practice in motor coordinates/codes (e.g., joint angles, activation patterns),
      which are effector dependent. In the present experiments, the task was to
      reproduce 1.3 s patterns of elbow flexions and extensions. An inter-manual
      transfer paradigm was used in Experiment 1 and an inter-manual practice paradigm
      was used in Experiment 2. The present results clearly indicated a strong
      advantage of effector transfer when the motor coordinates available during
      acquisition were reinstated (Experiment 1) and demonstrate that inter-manual
      practice with the same motor coordinates results in enhanced retention
      performance relative to transfer and practice where the same visual-spatial
      coordinates are used. These results demonstrate that the more effective movement
      code (motor or visual-spatial) is dependent on the movement sequence
      characteristics (e.g., difficulty, number of elements, and mode of control
      [preplanned or on-line]). These results are also interesting because they
      indicate, contrary to previous findings with more complex movement sequences,
      that an effective motor code can be developed relatively early in practice for
      rapid movement sequences.

PMID- 19389660
TI  - Stereoscopic shape discrimination is well preserved across changes in object
      size.
AB  - A single experiment evaluated human observers' ability to discriminate the shape
      of solid objects that varied in size and orientation in depth. The object shapes
      were defined by binocular disparity, Lambertian shading, and texture. The object
      surfaces were smoothly curved and had naturalistic shapes, resembling those of
      water-smoothed granite rocks. On any given trial, two objects were presented that
      were either the same or different in terms of shape. When the "same" objects were
      presented, they differed in their orientation in depth by 25 degrees , 45 degrees
      , or 65 degrees . The observers were required to judge whether any given pair of
      objects was the "same" or "different" in terms of shape. The size of the objects
      was also varied by amounts up to +/-40% relative to the standard size. The
      observers' shape discrimination performance was strongly affected by the
      magnitude of the orientation changes in depth - thus, their performance was
      viewpoint dependent. In contrast, the observers' shape discrimination abilities
      were only slightly affected by changes in the overall size of the objects. It
      appears that human observers can recognize the three-dimensional shape of objects
      in a manner that is relatively independent of size.

PMID- 19389661
TI  - Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a
      tract-based spatial statistics analysis.
AB  - BACKGROUND: Bipolar disorder (BD) is a common and debilitating condition, often
      beginning in adolescence. Converging evidence from genetic and neuroimaging
      studies indicates that white matter abnormalities may be involved in BD. In this
      study, we investigated white matter structure in adolescents with familial
      bipolar disorder using diffusion tensor imaging (DTI) and a whole brain analysis.
      METHODS: We analyzed DTI images using tract-based spatial statistics (TBSS), a
      whole-brain voxel-by-voxel analysis, to investigate white matter structure in 21
      adolescents with BD, who also were offspring of at least one parent with BD, and
      18 age- and IQ-matched control subjects. Fractional anisotropy (FA; a measure of
      diffusion anisotropy), trace values (average diffusivity), and apparent diffusion
      coefficient (ADC; a measure of overall diffusivity) were used as variables in
      this analysis. In a post hoc analysis, we correlated between FA values,
      behavioral measures, and medication exposure. RESULTS: Adolescents with BD had
      lower FA values than control subjects in the fornix, the left mid-posterior
      cingulate gyrus, throughout the corpus callosum, in fibers extending from the
      fornix to the thalamus, and in parietal and occipital corona radiata bilaterally.
      There were no significant between-group differences in trace or ADC values and no
      significant correlation between behavioral measures, medication exposure, and FA
      values. CONCLUSIONS: Significant white matter tract alterations in adolescents
      with BD were observed in regions involved in emotional, behavioral, and cognitive
      regulation. These results suggest that alterations in white matter are present
      early in the course of disease in familial BD.

PMID- 19389662
TI  - Characterization of a neutral polysaccharide with antioxidant capacity from red
      wine.
AB  - A neutral fraction (PS-SI) (0.3g/L) with MW of 74kDa, which contained galactose,
      arabinose, mannose, and glucose in the molar ratio of 1.0:0.6:0.4:0.2 was
      obtained by treatment of the whole polysaccharide extracted from red wine with
      cetrimide, followed by gel permeation chromatography. Spectroscopic and
      methylation analyses indicated that PS-SI is a mixture of neutral
      polysaccharides, consisting mainly of beta (1-->3)-linked galactopyranosyl
      residues, with side chains of galactopyranosyl residues at positions O-6.
      Arabinofuranosyl residues linked alpha (1-->5), alpha-mannopyranosyl and glucosyl
      residues appear to be components of different polysaccharides. The in vitro
      antioxidant capacity of fractions of wine polysaccharide was studied by hydroxyl
      radical scavenging and ORAC assays. Fraction PS-SI presented the strongest effect
      on hydroxyl radicals (IC(50)=0.21).

PMID- 19389663
TI  - [Role of the new lightweight prostheses in improving hernia repair].
AB  - The use of a prosthetic material to treat abdominal and/or thoracic disease has,
      to a great extent, resolved the problem created by the tissue defect itself and
      complications of recurrence. The most commonly used of these materials has been
      polypropylene in the form of a reticular mesh. This biomaterial, which boasts
      optimal biocompatibility, has been the object of constant modification aimed at
      better adapting it to the functional needs of the host tissue. Hence, the classic
      prostheses, nowadays known as heavyweights, are being gradually replaced by
      lighter materials with a simple spatial configuration and, more importantly, with
      a larger pore size (lightweight prostheses). Lightweight meshes are able to
      preserve abdominal wall compliance by generating less post-implant fibrosis and
      rigidity. However, further studies are still needed to achieve the ideal balance
      between material density and pore size. These two factors will determine the
      behaviour of these new prosthetic designs.

PMID- 19389664
TI  - Reduction of noise due to systematic uncertainties in 113mIn SPECT imaging using
      information theory.
AB  - SPECT images using radiopharmaceuticals are limited by noise caused by both
      random and systematic uncertainties. All the efforts so far have been directed
      only to minimize the random uncertainty and no attempt has ever been made to
      minimize the noise due to systematic uncertainty. As these radiopharmaceuticals
      encounter many systematic uncertainties during their formation, we constructed
      the covariance matrix with some of these systematic uncertainties for the gamma
      count rate of (113m)In. We describe the algorithm we have developed based on the
      technique of determinant inequalities and the concept of minimization of mutual
      information to process the covariance matrix element by element to minimize the
      noise caused by systematic uncertainty in the SPECT imaging of (113m)In and its
      utility to experimentalists to design and improve their process of measurement
      and instrumentation.

PMID- 19389665
TI  - Elevated blood lead levels in a riverside population in the Brazilian Amazon.
AB  - Lead (Pb) is recognized as one of the most toxic metals. Sources of Pb exposure
      have been widely documented in North America, and the removal of Pb additives
      from gasoline was reflected in a dramatic lowering of blood Pb concentration. In
      Latin America, the removal of Pb from gasoline resulted in decreased exposure,
      but Pb levels in many areas remain high due to occupational and environmental
      sources of exposure. While many of the Pb sources have been identified (mining,
      industries, battery recycling, lead-based paint, ceramics), new ones occasionally
      crop up. Here we report on blood Pb (B-Pb) levels in remote riverside communities
      of the Brazilian Amazon. Blood Pb (B-Pb) levels were determined in 448 persons
      from 12 villages of the Lower Tapajos River Basin, Para, Brazil. Socio
      demographic and dietary information, as well as occupational, residential and
      medical history was collected using an interview-administered questionnaire. B
      Pb, measured by ICP-MS, showed elevated concentrations. Mean B-Pb was 13.1
      microg/dL +/- 8.5, median B-Pb was 11.2 microg/dL and ranged from 0.59 to 48.3
      microg/dL. Men had higher B-Pb compared to women (median: 15.3 microg/dL vs 7.9
      microg/dL respectively). B-Pb increased with age for women, while it decreased
      for men. For both genders, B-Pb decreased with education. There were significant
      differences between villages. Exploratory analyses, using linear partition
      models, showed that for men B-Pb was lower among those who were involved in
      cattle-raising, and higher among those who hunted, farmed and fished. The
      distribution profile of B-Pb directed us towards artisanal transformation of
      manioc to flour (farinha), which requires heating in a large metal pan, with
      stirring primarily done by young men. In the village with the highest B-Pb,
      analysis of Pb concentrations (dry weight) of manioc (prior to transformation)
      and farinha (following transformation) from 6 houses showed a tenfold increase in
      Pb concentration (mean: 0.017 +/- 0.016 to 0.19 +/- 0.10 microg/g). This was
      confirmed in one of these villages where we sampled manioc paste (just before
      roasting) and the roasted farinha (0.05 microg/g vs 0.20 microg/g). While there
      may be other sources (ammunition, sinkers for fishing nets), the high
      concentrations in farinha, a dietary staple, assuredly makes an important
      contribution. Further action needs to reduce Pb sources in this region.

PMID- 19389666
TI  - Biliary cryptosporidiosis in a patient without HIV infection: endosonographic,
      cholangiographic, and histologic features (with video).

PMID- 19389667
TI  - Fuzzy controller design for passive continuous-time affine T-S fuzzy models with
      relaxed stability conditions.
AB  - In order to design a fuzzy controller for complex nonlinear systems, the work of
      this paper deals with developing the relaxed stability conditions for continuous
      time affine Takagi-Sugeno (T-S) fuzzy models. By applying the passivity theory
      and Lyapunov theory, the relaxed stability conditions are derived to guarantee
      the stability and passivity property of closed-loop systems. Based on these
      relaxed stability conditions, the synthesis of fuzzy controller design problem
      for passive continuous-time affine T-S fuzzy models can be easily solved via the
      Optimal Convex Programming Algorithm (OCPA) and Linear Matrix Inequality (LMI)
      technique. At last, a simulation example for the fuzzy control of a nonlinear
      synchronous generator system is presented to manifest the applications and
      effectiveness of proposed fuzzy controller design approach.

PMID- 19389668
TI  - Kobbe P, et al. Use of the 'reamer irrigator aspirator' system for non-infected
      tibial non-union after failed iliac crest grafting [Injury 2008;39(7):796-800].

PMID- 19389669
TI  - Citak M, et al. Navigated femoral anteversion measurements: a new intraoperative
      technique [Injury 2008;39(April (4)):467-71 (Epub 2008 February 12)].

PMID- 19389670
TI  - Ulnar collateral ligament injuries of the thumb: 10 years of surgical experience.
AB  - Over 10 years in our unit, 127 patients underwent surgical repair of an acute
      thumb ulnar collateral ligament (UCL) rupture for clinically unstable injuries or
      displaced avulsion fractures. Ultrasound was used when clinical diagnosis was
      uncertain. The male/female ratio was 3:2, with a mean age of 40 years (range: 12
      81 years). Most of them (> or =66%) were hyper-extension/abduction injuries. The
      most common cause was a fall (49%), followed by sports injuries; skiing accounted
      for only 2.4%. Ultrasound was 92% sensitive for UCL ruptures (positive predictive
      value (PPV) 99%). Over 99% of patients had a UCL rupture confirmed at surgery.
      Other findings included avulsion fractures (21%), dorsal capsular tears (57%) and
      dorsal capsule infolding (29%). The most common surgical complication was
      neurapraxia (6.5%). In our population, thumb UCL injuries are rarely caused by
      skiing. Ultrasound is a useful, sensitive adjunct in acute diagnosis. Dorsal
      capsular tears and joint interposition are common. Surgery provides excellent
      results with few long-term complications.

PMID- 19389671
TI  - Living with heart failure: an integrative review.
AB  - OBJECTIVES: To conduct an integrative review that explores the experiences and
      perceptions of patients who have heart failure to find any commonality that might
      enhance care giving to this patient group and areas for future research.
      BACKGROUND: Patients are expected to take responsibility for much of the day-to
      day management of their heart failure and modify their behaviour to maintain and
      improve their health. The degree of responsibility which patients can take is to
      a large extent dependant on how they see themselves in the context of their new
      situation. Limited research has been undertaken about how patients come to terms
      with their new condition and subsequent 'new self', but this has not been linked
      to patients' ability to take more responsibility. This review will integrate this
      notion of self-care, personal responsibility and the implications of this for
      nursing care, as this is not identified in current guidelines. DESIGN AND DATA
      SOURCES: Using an integrative review method, Ovid MEDLINE, CINAHL, EMBASE, AMED,
      HMIC, BNI and PsycINFO databases were searched from January 1985 to May 2008. 18
      papers were selected that most clearly reflected the concept of understanding the
      patient's experience of living with heart failure. RESULTS: Patients appear to
      undergo a process of taking on a new identity, 'a new self'. From the review five
      conceptual categories emerge: diagnosis and manifestations of heart failure;
      perceptions of day-to-day life; coping behaviours; role of others and concept of
      self which influences all of the other categories. This maps a journey, as the
      individual experiences heart failure; their success or failure at adapting to
      this new sense of self, will influence self-care behaviours. CONCLUSIONS:
      Literature that explores understanding the patient's experiences of living with
      heart failure, taking on a new identity and the influence of this on their self
      care behaviour, is limited. The integration of the new condition with patient's
      sense of self is likely to a have a major impact on the effectiveness of
      treatments offered. An essential and ethical care component for patients with
      heart failure should be an ongoing assessment of their experience of the
      situation that they live with.

PMID- 19389672
TI  - Sex differences of carotid intima-media thickness in healthy children and
      adolescents.
AB  - OBJECTIVES: In pediatric cardiovascular health prevention non-invasive
      diagnostics of subclinical atherosclerosis is essential for screenings and
      interventional purposes. Increased carotid artery intima-media thickness (IMT)
      has been reported in the presence of cardiovascular risk factors in childhood.
      However, little information exists regarding the age and sex distribution of IMT
      as stated in adults. This study investigates first, if IMT sonography is reliable
      and feasible; second, calculates sex- and age-specific percentiles; third, re
      confirms IMT associations to cardiovascular risk parameters and analyses
      predictors for age-adjusted IMT. METHODS: 267 healthy pupils (age 6-17 years)
      were examined prospectively. Standardized IMT sonography and offline analysis
      were performed. Anthropometric data, BMI, body composition, blood pressure were
      taken; Spearman's rank correlation coefficient and multiple stepwise linear
      regression analyses were calculated. RESULTS: Intra-observer variability: CV was
      2.42% (n=132; MD=0.012mm; r=0.849); inter-observer variability: CV was 1.71%
      (n=75; MD=0.013mm; r=0.780). Age- and sex-specific IMT percentiles for age groups
      8/9 to 14/15 years were calculated. IMT values were higher in boys than in girls
      at the same age. Systolic blood pressure and IMT were positively related in boys
      (p<0.001, r=0.31) and girls (p=0.005, r=0.24). Predictors for age-adjusted IMT:
      systolic blood pressure was shown to be a predictor (r(2)=0.10, beta=0.31,
      p<0.001) in boys; weight emerged as a predictor (r(2)=0.19, beta=0.43, p<0.001)
      in girls. CONCLUSION: The main study benefit is the provision of IMT percentiles
      for both sexes for the age groups 8/9 to 14/15 years. The results suggest that
      sex-specific prevention should be given further attention in a comprehensive and
      multi-risk parameters approach.

PMID- 19389674
TI  - Longitudinal study on premature atherosclerosis in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVES: To determine risk factors of accelerated atherosclerosis and
      progression of intima-media thickness (IMT) in patients with systemic lupus
      erythematosus (SLE). METHODS: 74 SLE patients, age ranging from 13 to 69 years,
      and 74 age- and sex-matched controls were included. IMT of the common carotid
      artery was determined by B-mode ultrasound imaging. Traditional risk factors for
      atherosclerosis and disease-related factors were recorded. Cardiovascular risk
      was estimated using systematic coronary risk evaluation (SCORE). Markers of
      inflammation (C-reactive protein, CRP) and endothelial activation
      (thrombomodulin, vascular cell adhesion molecule-1, and von Willebrand factor)
      were determined. Measurements were repeated in 52 patients after a follow-up of
      32+/-7 months. RESULTS: IMT was increased in SLE patients compared to controls.
      Prevalence of smoking and hypertension, use of lipid-lowering drugs and SCORE
      were higher in patients, as well as levels of CRP and markers of endothelial
      activation. The age-related increase in IMT was significantly higher in patients
      than in controls. In multivariate analysis, age and disease duration was
      independently related to IMT. Increase in IMT during follow-up was related to age
      only. CONCLUSION: The age-related increase in IMT is higher in SLE, indicating
      that atherosclerosis is accelerated in SLE patients. This is mainly due to
      disease-related risk factors, as disease duration was independently associated
      with IMT.

PMID- 19389675
TI  - The Watanabe heritable hyperlipidemic (WHHL) rabbit, its characteristics and
      history of development: a tribute to the late Dr. Yoshio Watanabe.
AB  - Professor Yoshio Watanabe, who developed the WHHL rabbit, died on December 13,
      2008. He had contributed to studies of lipoprotein metabolism and
      atherosclerosis, and to the development of hypolipidemic and/or anti
      atherosclerotic compounds. WHHL rabbits show hypercholesterolemia due to
      deficiency of LDL receptors, and very similar lipoprotein metabolism to humans.
      The incidences of coronary atherosclerosis and myocardial infarction in the
      original WHHL rabbits were very low. After three rounds of selective breeding,
      the coronary plaques changed to fibroatheromas with thin fibrous caps and
      myocardial infarction developed spontaneously. In studies with WHHL rabbits,
      plaque-stabilizing effects of statins were proved. In this review, we admire his
      achievements and describe the history of studies using WHHL rabbits.

PMID- 19389676
TI  - Conditional linkage and genome-wide association studies identify UGT1A1 as a
      major gene for anti-atherogenic serum bilirubin levels--the Framingham Heart
      Study.
AB  - OBJECTIVE AND METHODS: Low bilirubin levels are significantly associated with
      cardiovascular diseases (CVD). In previous genome-wide linkage studies we
      identified a major locus on chromosome 2q harboring the candidate gene UDP
      glucuronosyltransferase (UGT1A1). The activity of this enzyme is significantly
      influenced by a TA-repeat polymorphism in the promoter of the gene. In a
      prospective study individuals with genotype (TA)7/(TA)7 had significantly higher
      bilirubin levels and approximately one-third the risk of CVD as carriers of the
      wildtype (TA)6 allele. In the present study we performed a conditional linkage
      study to investigate whether this polymorphism explains the observed linkage peak
      and extended our analysis by a genome-wide association study on bilirubin levels
      in 1345 individuals. RESULTS: After adjustment for the bilirubin variance
      explained by this polymorphism, the LOD score on chromosome 2q dropped from 3.8
      to 0.4, demonstrating that this polymorphism explains the previous linkage
      result. For the genome-wide association study, the closest marker to UGT1A1 was
      in the top ranking SNPs. The association became even stronger when we considered
      the TA-repeat polymorphism in the analysis (p=2.68 x 10(-53)). Five other SNPs in
      other regions reached genome-wide significance without obvious connection to
      bilirubin metabolism. CONCLUSIONS: Our studies suggest that UGT1A1 may be the
      major gene with strong effects on bilirubin levels and the TA-repeat polymorphism
      might be the key polymorphism within the gene controlling bilirubin levels. Since
      this polymorphism has a high frequency and a substantial impact on the
      development of CVD, the gene might be an important drug target.

PMID- 19389677
TI  - Experimental validation of a tibiofemoral model for analyzing joint force
      distribution.
AB  - A computational model of the tibiofemoral joint utilizing the discrete element
      analysis method has been developed and validated with human cadaveric knees. The
      computational method can predict load distributions to within a root mean square
      error (RMSE) of 3.6%. The model incorporates subject-specific joint geometry and
      the health of the subjects' articular cartilage to determine the cartilage
      stiffness. It also includes the collateral and cruciate ligaments and utilizes
      stiffness values derived from literature for these elements. Comparisons of the
      total load, peak load, and peak load location for axial, varus, and valgus
      loading conditions confirmed that there was less than 4% RMSE between the
      analytical and experimental results. The model presented in this paper can
      generate results with minimal computational time and it can be used as a non
      invasive method for characterizing and monitoring subject-specific knee loading
      patterns.

PMID- 19389678
TI  - From neuromuscular activation to end-point locomotion: An artificial neural
      network-based technique for neural prostheses.
AB  - Neuroprostheses, implantable or non-invasive ones, are promising techniques to
      enable paralyzed individuals with conditions, such as spinal cord injury or spina
      bifida (SB), to control their limbs voluntarily. Direct cortical control of
      invasive neuroprosthetic devices and robotic arms have recently become feasible
      for primates. However, little is known about designing non-invasive, closed-loop
      neuromuscular control strategies for neural prostheses. Our goal was to
      investigate if an artificial neural network-based (ANN-based) model for closed
      loop-controlled neural prostheses could use neuromuscular activation recorded
      from individuals with impaired spinal cord to predict their end-point gait
      parameters (such as stride length and step width). We recruited 12 persons with
      SB (5 females and 7 males) and collected their neuromuscular activation and end
      point gait parameters during overground walking. Our results show that the
      proposed ANN-based technique can achieve a highly accurate prediction (e.g., R
      values of 0.92-0.97, ANN (tansig+tansig) for single composition of data sets) for
      altered end-point locomotion. Compared to traditional robust regression, this
      technique can provide up to 80% more accurate prediction. Our results suggest
      that more precise control of complex neural prostheses during locomotion can be
      achieved by engaging neuromuscular activity as intrinsic feedback to generate end
      point leg movement. This ANN-based model allows a seamless incorporation of
      neuromuscular activity, detected from paralyzed individuals, to adaptively
      predict their altered gait patterns, which can be employed to provide closed-loop
      feedback information for neural prostheses.

PMID- 19389679
TI  - Decoupled pelvis rotation in sitting: a passive motion technique that regulates
      buttock load associated with pressure ulcer development.
AB  - Wheelchair-users who cannot reposition themselves often suffer from pressure
      ulcers which are places of tissue breakdown in the buttock region under the
      sacrum and ischial tuberosities. Periodic pressure relief is needed to recover
      the buttock tissue from continuous deformation and impairment of tissue
      perfusion. Because pelvis alignment directly affects body posture and buttock
      load, a passive motion technique was developed that adjusts pelvis orientation
      independent from the trunk and seat support. This study investigates the effects
      of the so-called decoupled pelvis rotation (DPR) on the loads at the buttock-seat
      interface and evaluates whether this technique is applicable to regulate buttock
      load in sitting. Eighteen healthy male subjects participated in this study.
      Experiments were performed with a computer-aided adjustable simulator chair,
      instrumented with a concept of DPR. Measurements involved quasi-static actuated
      pelvis movements in the sagittal and frontal plane. Pelvis orientation, buttock
      interface pressures, seat reaction forces and centre of pressure were
      simultaneously measured. As a result of the induced passive pelvis movements, the
      pelvis rotated 19+/-2 degrees and 9+/-2 degrees in the sagittal and frontal
      plane, respectively. Significant relations were found between pelvis rotation and
      most quantities of buttock load. Findings suggest that DPR is an effective
      technique to regulate buttock load in able-bodied individuals. For clinical
      application, this technique is still to be evaluated on individuals who cannot
      functionally reposition themselves. Impairments to the neuromuscular function
      influence postural response from chair adjustments which makes clinical
      investigation necessary.

PMID- 19389680
TI  - Noninvasive intracranial compliance from MRI-based measurements of transcranial
      blood and CSF flows: indirect versus direct approach.
AB  - Intracranial compliance (ICC) determines the ability of the intracranial
      compartment to accommodate an increase in volume without a large increase in
      intracranial pressure (ICP). The clinical utilization of ICC is limited by the
      invasiveness of current measurement. Several investigators attempted to estimate
      ICC noninvasively, from magnetic resonance imaging (MRI) measurements of cerebral
      blood and cerebral spinal fluid flows, either using indirect measures of ICC or
      directly by measuring the ratio of the changes in intracranial volume and
      pressure during the cardiac cycle. The indirect measures include the phase lag
      between the cerebrospinal fluid (CSF) and its driving force, either arterial
      inflow or net transcranial blood flow. This study compares the sensitivity of
      phase-based and amplitude-based measures of ICC to changes in ICC. In vivo
      volumetric blood and CSF flows measured by MRI phase contrast from healthy
      volunteers and from patients with elevated ICP were used for the comparison. An
      RLC circuit model of the craniospinal system was utilized to simulate the effect
      of a change in ICC on the CSF flow waveform. The simulations demonstrated that
      amplitude-based measures of ICC are considerably more sensitive than phase-based
      measures, and among the amplitude-based measures, the ICC index provides the most
      reliable estimate of ICC.

PMID- 19389681
TI  - A mathematical model for predicting ultrasonic measurement of total knee
      replacement contact areas.
AB  - A simple mathematical model was developed to characterize diagnostic ultrasound
      behavior at two-body interfaces of known geometry. The model was based on a 2-D
      curved-on-flat geometry comprising an infinitely long circular cylinder indenting
      a flat infinite half-space creating a known contact width W(0). The effects of
      indenter radius R(F) ultrasound resonance wavelength lambda/2, and ultrasound
      beam thickness BT on the size of the predicted interfacial contact width W(1)
      were investigated. Since the model was purely geometric in nature, material
      properties of the mating bodies were not considered. A theoretical sensitivity
      analysis was performed on the model using geometries representative of
      commercially available orthopedic total knee replacements (TKRs) and typical
      diagnostic ultrasound resolutions. This investigation was part of an ongoing
      project to develop an engineering design tool for measuring surface contact areas
      at the tibio-femoral interfaces of clinically employed TKR prostheses.

PMID- 19389682
TI  - Effect of head shape variations among individuals on the EEG/MEG forward and
      inverse problems.
AB  - We study the effect of the head shape variations on the
      EEG/magnetoencephalography (MEG) forward and inverse problems. We build a random
      head model such that each sample represents the head shape of a different
      individual and solve the forward problem assuming this random head model, using a
      polynomial chaos expansion. The random solution of the forward problem is then
      used to quantify the effect of the geometry when the inverse problem is solved
      with a standard head model. The results derived with this approach are valid for
      a continuous family of head models, rather than just for a set of cases. The
      random model consists of three random surfaces that define layers of different
      electric conductivity, and we built an example based on a set of 30 deterministic
      models from adults. Our results show that for a dipolar source model, the effect
      of the head shape variations on the EEG/MEG inverse problem due to the random
      head model is slightly larger than the effect of the electronic noise present in
      the sensors. The variations in the EEG inverse problem solutions are due to the
      variations in the shape of the volume conductor, while the variations in the MEG
      inverse problem solutions, larger than the EEG ones, are caused mainly by the
      variations of the absolute position of the sources in a coordinate system based
      on anatomical landmarks, in which the magnetometers have a fixed position.

PMID- 19389683
TI  - Denoising by averaging reconstructed images: application to magnetic resonance
      images.
AB  - A novel denoising approach is proposed that is based on averaging reconstructed
      images. The approach first divides the spectrum of the image to be denoised into
      different parts. From every such partial spectrum is then reconstructed an image
      using a 2-D singularity function analysis model. By expressing each of the
      reconstructed images as the sum of the same noise-free image and a different
      smaller noise, the denoising is achieved through averaging the reconstructed
      images. The theoretical formulation and experimental results on both simulated
      and real images consistently demonstrated that the proposed approach can
      efficiently denoise while maintaining high image quality, and presents
      significant advantages over conventional denoising methods.

PMID- 19389684
TI  - Local scale exponents of blood pressure and heart rate variability by detrended
      fluctuation analysis: effects of posture, exercise, and aging.
AB  - Heart rate self-affinity is often assessed by detrended fluctuations analysis,
      obtaining two coefficients only: a short-term (alpha(1)) exponent and a long-term
      (alpha(2)) exponent. Our aim is to show the limits of this approach and
      alternatively propose the estimation of the whole spectrum of local exponents
      alpha(n) for heart rate and blood pressure. To illustrate the advantages of this
      approach, we assess the effects of autonomic activations and age on alpha(n). We
      measured ECG and arterial pressure in 60 volunteers for 10 min, considering three
      conditions at increasing sympathetic activation: supine rest, sitting, and
      sitting during exercise. We computed alpha(n) of R-R intervals and systolic,
      mean, and diastolic blood pressures, as the slope of the detrended fluctuations
      function in a log-log plot. Volunteers were divided into age groups and compared.
      Results indicate that: 1) alpha(1) cannot be defined because short-term
      coefficients decrease with n, while alpha(2) cannot be defined only for blood
      pressure during supine rest; 2) heart rate and blood pressure scaling structures
      differ during supine rest but not during exercise; and 3) age effects appear
      mainly in supine rest, explaining discrepant results in literature. In
      conclusion, we recommend estimating the whole alpha(n) spectrum before possibly
      providing the "two-exponent" description only.

PMID- 19389685
TI  - Computer-assisted preoperative planning for reduction of proximal femoral
      fracture using 3-D-CT data.
AB  - This paper describes procedures for repositioning calculations of fractured bone
      fragments using 3-D-computed tomography (CT), aimed at preoperative planning for
      computer-guided fracture reduction of the proximal femur. Fracture boundaries of
      the bone fragments, as "fracture lines (FLs)," and the mirror-transformed
      contralateral femur shape extracted from 3-D-CT were used for repositioning of
      the fragments. We first describe a method for extracting FLs based on 3-D
      curvature analysis and then formulate repositioning methods based on registration
      of bone fragments using the following three constraints: 1) contralateral (CL)
      femur shape; 2) FLs; and 3) both CL femur shape and fracture lines, as "both
      constraints". We performed experiments using CT datasets from five simulated and
      four real patients with proximal femoral fracture. We evaluated the rotation
      error in reposition calculations and the contact ratio between repositioned
      fragment boundaries, which are crucial for the recovery of proper functional axes
      and bone adhesion of fragments, respectively. Experimental results showed that
      good accuracy and stability were attainable when registration using both
      constraints was performed after registration using the fracture-line constraint.
      On average, 6.0 degrees +/-0.8 degrees in rotation error and 89%+/-3 % in contact
      ratio were obtained without providing precise initial values.

PMID- 19389686
TI  - Enhancing the standard operating range of a Placido disk videokeratoscope for
      corneal surface estimation.
AB  - Corneal topography estimation that is based on the Placido disk principle relies
      on good quality of precorneal tear film and sufficiently wide eyelid (palpebral)
      aperture to avoid reflections from eyelashes. However, in practice, these
      conditions are not always fulfilled resulting in missing regions, smaller corneal
      coverage, and subsequently poorer estimates of corneal topography. Our aim was to
      enhance the standard operating range of a Placido disk videokeratoscope to obtain
      reliable corneal topography estimates in patients with poor tear film quality,
      such as encountered in those diagnosed with dry eye, and with narrower palpebral
      apertures as in the case of Asian subjects. This was achieved by incorporating in
      the instrument's own topography estimation algorithm an image processing
      technique that comprises a polar-domain adaptive filter and a morphological
      closing operator. The experimental results from measurements of test surfaces and
      real corneas showed that the incorporation of the proposed technique results in
      better estimates of corneal topography, and, in many cases, to a significant
      increase in the estimated coverage area making such an enhanced videokeratoscope
      a better tool for clinicians.

PMID- 19389687
TI  - Modulation of conduction velocity by nonmyocytes in the low coupling regime.
AB  - This paper explores the conditions under which nonmyocytes, when electrically
      coupled to myocytes, act as a passive load during the depolarization phase. Using
      theoretical arguments and numerical simulations in a tissue incorporating
      fibroblasts, the passive load approximation is shown to be accurate at low
      coupling conductances (< 2 nS). In this case, the effect on conduction velocity
      can be expressed as a function of the elevation in resting potential and the
      coupling only.

PMID- 19389688
TI  - On ECG signal compression with 1-D multiscale recurrent patterns allied to
      preprocessing techniques.
AB  - This paper presents the results of a multiscale pattern-matching-based ECG
      encoder, which employs simple preprocessing techniques for adapting the input
      signal. Experiments carried out with records from the Massachusetts Institute of
      Technology-Beth Israel Hospital database show that the proposed scheme is
      effective, outperforming some state-of-the-art schemes described in the
      literature.

PMID- 19389689
TI  - An offline evaluation of the autoregressive spectrum for electrocorticography.
AB  - Electrical signals acquired from the cortical surface, or electrocorticography
      (ECoG), exhibit high spatial and temporal resolution and are valuable for mapping
      brain activity, detecting irregularities, and controlling a brain-computer
      interface. As with scalp-recorded EEG, much of the identified information content
      in ECoG is manifested as amplitude modulations of specific frequency bands.
      Autoregressive (AR) spectral estimation has proven successful for modeling the
      well-defined and comparatively limited EEG spectrum. However, because the ECoG
      spectrum is significantly more extensive with yet undefined dynamics, it cannot
      be assumed that the ECoG spectrum can be accurately estimated using the same AR
      model parameters that are valid for analogous EEG studies. This study provides an
      offline evaluation of AR modeling of ECoG signals for detecting tongue movements.
      The resulting model parameters can serve as a reference for related AR spectral
      analysis of ECoG signals.

PMID- 19389690
TI  - Regularized estimation of retinal vascular oxygen tension from phosphorescence
      images.
AB  - The level of retinal oxygenation is potentially an important cue to the onset or
      presence of some common retinal diseases. An improved method for assessing oxygen
      tension in retinal blood vessels from phosphorescence lifetime imaging data is
      reported in this paper. The optimum estimate for phosphorescence lifetime and
      oxygen tension is obtained by regularizing the least-squares (LS) method. The
      estimation method is implemented with an iterative algorithm to minimize a
      regularized LS cost function. The effectiveness of the proposed method is
      demonstrated by applying it to simulated data as well as image data acquired from
      rat retinas. The method is shown to yield estimates that are robust to noise and
      whose variance is lower than that obtained with the classical LS method.

PMID- 19389691
TI  - Characterizing torso shape deformity in scoliosis using structured splines
      models.
AB  - This paper describes a method of characterizing the torso shape deformity
      associated with scoliosis by both its type and severity. This problem is
      challenging because regular human torsos show an astounding range of variations
      that is only compounded by scoliosis, and it is difficult to isolate natural
      shape variations from those caused by scoliosis. Torso shape characterization is
      important in the clinical management of scoliosis because torso aesthetics is a
      key concern that influences a patient's quality of life. Our method involves
      modeling 3-D torso range images into structured sequences of 3-D spline curves
      stacked along the spine. We obtain local shape measures from points of maximal
      curvature (dominant points) along each torso cross section by evaluating the
      relative symmetry of the spline curve at that cross section. This results in a
      scalable characterization scheme for torso deformity type and a measure of torso
      deformity severity. We assess the accuracy and precision of this shape
      characterization scheme, and its relationship to the actual deformities present
      in the underlying spine.

PMID- 19389693
TI  - A novel template reduction approach for the K-nearest neighbor method.
AB  - The K-nearest neighbor (KNN) rule is one of the most widely used pattern
      classification algorithms. For large data sets, the computational demands for
      classifying patterns using KNN can be prohibitive. A way to alleviate this
      problem is through the condensing approach. This means we remove patterns that
      are more of a computational burden but do not contribute to better classification
      accuracy. In this brief, we propose a new condensing algorithm. The proposed idea
      is based on defining the so-called chain. This is a sequence of nearest neighbors
      from alternating classes. We make the point that patterns further down the chain
      are close to the classification boundary and based on that we set a cutoff for
      the patterns we keep in the training set. Experiments show that the proposed
      approach effectively reduces the number of prototypes while maintaining the same
      level of classification accuracy as the traditional KNN. Moreover, it is a simple
      and a fast condensing algorithm.

PMID- 19389694
TI  - Fault detection and diagnosis based on modeling and estimation methods.
AB  - This paper investigates the problem of fault detection and diagnosis in a class
      of nonlinear systems with modeling uncertainties. A nonlinear observer is first
      designed for monitoring fault. Radial basis function (RBF) neural network is used
      in this observer to approximate the unknown nonlinear dynamics. When a fault
      occurs, another RBF is triggered to capture the nonlinear characteristics of the
      fault function. The fault model obtained by the second neural network (NN) can be
      used for identifying the failure mode by comparing it with any known failure
      modes. Finally, a simulation example is presented to illustrate the effectiveness
      of the proposed scheme.

PMID- 19389692
TI  - Modulation of axonal excitability by high-frequency biphasic electrical current.
AB  - The modulation of axonal excitability by high-frequency biphasic (HFB) electrical
      current was analyzed using a lumped-circuit model of the myelinated axon based on
      Schwarz-Reid-Bostock (SRB) equations. The results show that axonal excitability
      could be either increased or decreased by HFB current depending on the current
      intensity. The increase of axonal excitability is due to the high level of sodium
      channel activation, whereas the activation of both fast and slow potassium
      channels plays an important role in decreasing axonal excitability. As the HFB
      current intensity increases, the location determining the axonal excitability
      changes from the nodes under the electrode within the "main lobe" region of the
      activating function to the nodes away from the electrode in the "side lobe"
      region of the activating function. This simulation study also shows that the
      modulation of axonal excitability by HFB electrical current could be potentially
      useful to selectively activate the small nerve fibers in a compound nerve trunk
      without activating the large fibers. Understanding how HFB electrical current
      modulates the axonal excitability will further elucidate the possible mechanisms
      underlying the nerve conduction block induced by HFB electrical current.

PMID- 19389695
TI  - Geometric video approximation using weighted matching pursuit.
AB  - In recent years, works on geometric multidimensional signal representations have
      established a close relation with signal expansions on redundant dictionaries.
      For this purpose, matching pursuits (MP) have shown to be an interesting tool.
      Recently, most important limitations of MP have been underlined, and alternative
      algorithms like weighted-MP have been proposed. This work explores the use of
      weighted-MP as a new framework for motion-adaptive geometric video
      approximations. We study a novel algorithm to decompose video sequences in terms
      of few, salient video components that jointly represent the geometric and motion
      content of a scene. Experimental coding results on highly geometric content
      reflect how the proposed paradigm exploits spatio-temporal video geometry. Two
      dimensional weighted-MP improves the representation compared to those based on 2
      D MP. Furthermore, the extracted video components represent relevant visual
      structures with high saliency. In an example application, such components are
      effectively used as video descriptors for the joint audio-video analysis of
      multimedia sequences.

PMID- 19389696
TI  - A new statistical detector for DWT-based additive image watermarking using the
      Gauss-hermite expansion.
AB  - Traditional statistical detectors of the discrete wavelet transform (DWT)-based
      image watermarking use probability density functions (PDFs) that show inadequate
      matching with the empirical PDF of image coefficients in view of the fact that
      they use a fixed number of parameters. Hence, the decision values obtained from
      the estimated thresholds of these detectors provide substandard detection
      performance. In this paper, a new detector is proposed for the DWT-based additive
      image watermarking, wherein a PDF based on the Gauss-Hermite expansion is used,
      in view of the fact that this PDF provides a better statistical match to the
      empirical PDF by utilizing an appropriate number of parameters estimated from
      higher-order moments of the image coefficients. The decision threshold and the
      receiver operating characteristics are derived for the proposed detector.
      Experimental results on test images demonstrate that the proposed watermark
      detector performs better than other standard detectors such as the Gaussian and
      generalized Gaussian (GG), in terms of the probabilities of detection and false
      alarm as well as the efficacy. It is also shown that detection performance of the
      proposed detector is more robust than the competitive GG detector in the case of
      compression, additive white Gaussian noise, filtering, or geometric attack.

PMID- 19389697
TI  - Stabilization of parametric active contours using a tangential redistribution
      term.
AB  - Depending on implementation, active contours have been classified as geometric or
      parametric active contours. Parametric contours, irrespective of representation,
      are known to suffer from the problem of irregular bunching and spacing out of
      curve points during the curve evolution. In a spline-based implementation of
      active contours, this leads to occasional formation of loops locally, and
      subsequently the curve blows up due to instabilities. In this paper, we analyze
      the reason for this problem and propose a solution to alleviate the same. We
      propose an ordinary differential equation (ODE) for controlling the curve
      parametrization during evolution by including a tangential force. We show that
      the solution of the proposed ODE is bounded. We demonstrate the effectiveness of
      the proposed method for segmentation and tracking tasks on closed as well as open
      contours.

PMID- 19389698
TI  - Adaptive primal-dual genetic algorithms in dynamic environments.
AB  - Recently, there has been an increasing interest in applying genetic algorithms
      (GAs) in dynamic environments. Inspired by the complementary and dominance
      mechanisms in nature, a primal-dual GA (PDGA) has been proposed for dynamic
      optimization problems (DOPs). In this paper, an important operator in PDGA, i.e.,
      the primal-dual mapping (PDM) scheme, is further investigated to improve the
      robustness and adaptability of PDGA in dynamic environments. In the improved
      scheme, two different probability-based PDM operators, where the mapping
      probability of each allele in the chromosome string is calculated through the
      statistical information of the distribution of alleles in the corresponding gene
      locus over the population, are effectively combined according to an adaptive
      Lamarckian learning mechanism. In addition, an adaptive dominant replacement
      scheme, which can probabilistically accept inferior chromosomes, is also
      introduced into the proposed algorithm to enhance the diversity level of the
      population. Experimental results on a series of dynamic problems generated from
      several stationary benchmark problems show that the proposed algorithm is a good
      optimizer for DOPs.

PMID- 19389699
TI  - A modified matched filter with double-sided thresholding for screening
      proliferative diabetic retinopathy.
AB  - The early diagnosis of proliferative diabetic retinopathy (PDR), a common
      complication of diabetes that damages the retina, is crucial to the protection of
      the vision of diabetes sufferers. The onset of PDR is signaled by the appearance
      of neovascular net. Such neovascular nets might be identified using retinal
      vessel extraction techniques. The commonly used matched filter methods often
      produce false positive detections of neovascular nets due to their proneness to
      detect nonline edges as well as lines. In this paper, we propose a modified
      matched filter for retinal vessel extraction that applies a local vessel cross
      section analysis using double-sided thresholding to reduce false responses to
      nonline edges. Our proposed modified matched filters demonstrated higher true
      positive rate and lesser false detection than existing matched-filter-based
      schemes in vessel extraction.

PMID- 19389700
TI  - Caspase-cleaved tau expression induces mitochondrial dysfunction in immortalized
      cortical neurons: implications for the pathogenesis of Alzheimer disease.
AB  - In Alzheimer disease (AD) mitochondrial abnormalities occur early in the
      pathogenic process and likely play a significant role in disease progression. Tau
      is a microtubule-associated protein that is abnormally processed in AD, and a
      connection between tau pathology and mitochondrial impairment has been proposed.
      However, few studies have examined the relationship between pathological forms of
      tau and mitochondrial dysfunction. We recently demonstrated that inducible
      expression of tau truncated at Asp-421 to mimic caspase cleavage (T4C3) was toxic
      to immortalized cortical neurons compared with a full-length tau isoform (T4). In
      this study we investigated the effects of T4C3 on mitochondrial function.
      Expression of T4C3 induced mitochondrial fragmentation and elevated oxidative
      stress levels in comparison with T4-expressing cells. Thapsigargin treatment of
      T4 or T4C3 cells, which causes an increase in intracellular calcium levels,
      resulted in a significant decrease in mitochondrial potential and loss of
      mitochondrial membrane integrity in T4C3 cells when compared with cells
      expressing T4. The mitochondrial fragmentation and mitochondrial membrane damage
      were ameliorated in T4C3 cells by pretreatment with cyclosporine A or FK506,
      implicating the calcium-dependent phosphatase calcineurin in these pathogenic
      events. Increased calcineurin activity has been reported in AD brain, and thus,
      inhibition of this phosphatase may provide a therapeutic target for the treatment
      of AD.

PMID- 19389701
TI  - Target gene specificity of USF-1 is directed via p38-mediated phosphorylation
      dependent acetylation.
AB  - How transcription factors interpret the output from signal transduction pathways
      to drive distinct programs of gene expression is a key issue that underpins
      development and disease. The ubiquitously expressed basic-helix-loop-helix
      leucine zipper upstream stimulating factor-1 binds E-box regulatory elements
      (CANNTG) to regulate a wide number of gene networks. In particular, USF-1 is a
      key component of the tanning process. Following UV irradiation, USF-1 is
      phosphorylated by the p38 stress-activated kinase on threonine 153 and directly
      up-regulates expression of the POMC, MC1R, TYR, TYRP-1 and DCT genes. However,
      how phosphorylation on Thr-153 might affect the activity of USF-1 is unclear.
      Here we show that, in response to DNA damage, oxidative stress and cellular
      infection USF-1 is acetylated in a phospho-Thr-153-dependent fashion. Phospho
      acetylated USF-1 is nuclear and interacts with DNA but displays altered gene
      regulatory properties. Phospho-acetylated USF-1 is thus proposed to be associated
      with loss of transcriptional activation properties toward several target genes
      implicated in pigmentation process and cell cycle regulation. The identification
      of this critical stress-dependent USF-1 modification gives new insights into
      understanding USF-1 gene expression modulation associated with cancer
      development.

PMID- 19389702
TI  - Activation of an olfactory receptor inhibits proliferation of prostate cancer
      cells.
AB  - Olfactory receptors (ORs) are expressed not only in the sensory neurons of the
      olfactory epithelium, where they detect volatile substances, but also in various
      other tissues where their potential functions are largely unknown. Here, we
      report the physiological characterization of human OR51E2, also named prostate
      specific G-protein-coupled receptor (PSGR) due to its reported up-regulation in
      prostate cancer. We identified androstenone derivatives as ligands for the
      recombinant receptor. PSGR can also be activated with the odorant beta-ionone.
      Activation of the endogenous receptor in prostate cancer cells by the identified
      ligands evoked an intracellular Ca2+ increase. Exposure to beta-ionone resulted
      in the activation of members of the MAPK family and inhibition of cell
      proliferation. Our data give support to the hypothesis that because PSGR
      signaling could reduce growth of prostate cancer cells, specific receptor ligands
      might therefore be potential candidates for prostate cancer treatment.

PMID- 19389703
TI  - The functional roles of the His247 and His281 residues in folate and proton
      translocation mediated by the human proton-coupled folate transporter SLC46A1.
AB  - This report addresses the functional role of His residues in the proton-coupled
      folate transporter (PCFT; SLC46A1), which mediates intestinal folate absorption.
      Of ten His residues, only H247A and H281A mutations altered function. The folic
      acid influx Kt at pH 5.5 for H247A was downward arrow 8.4-fold. Although wild
      type (WT)-PCFT Ki values varied among the folates, Ki values were much lower and
      comparable for H247-A, -R, -Q, or -E mutants. Homology modeling localized His247
      to the large loop separating transmembrane domains 6 and 7 at the cytoplasmic
      entrance of the translocation pathway in hydrogen-bond distance to Ser172. The
      folic acid influx Kt for S172A-PCFT was decreased similar to H247A. His281 faces
      the extracellular region in the seventh transmembrane domain. H281A-PCFT results
      in loss-of-function due to approximately 12-fold upward arrow in the folic acid
      influx Kt. When the pH was decreased from 5.5 to 4.5, the WT-PCFT folic acid
      influx Kt was unchanged, but the Kt decreased 4-fold for H281A. In
      electrophysiological studies in Xenopus oocytes, both WT-PCFT- and H281A-PCFT
      mediated folic acid uptake produced current and acidification, and both exhibited
      a low level of folate-independent proton transport (slippage). Slippage was
      markedly increased for the H247A-PCFT mutant. The data suggest that disruption of
      the His247 to Ser172 interaction results in a PCFT conformational alteration
      causing a loss of selectivity, increased substrate access to a high affinity
      binding pocket, and proton transport in the absence of a folate gradient. The
      His281 residue is not essential for proton coupling but plays an important role
      in PCFT protonation, which, in turn, augments folate binding to the carrier.

PMID- 19389704
TI  - Processing of the phalloidin proprotein by prolyl oligopeptidase from the
      mushroom Conocybe albipes.
AB  - The peptide toxins of poisonous Amanita mushrooms are bicyclic octapeptides
      (amatoxins) or heptapeptides (phallotoxins). In Amanita bisporigera, alpha
      amanitin and phallacidin are synthesized as 35- and 34-amino acid proproteins,
      respectively, in which the amino acid sequences found in the mature toxins are
      flanked by conserved amino acid sequences. The presence of invariant Pro residues
      immediately upstream of the toxin regions and as the last predicted amino acid in
      the toxin regions themselves suggests that a Pro-specific peptidase is
      responsible for the initial post-translational processing of the Amanita toxin
      proproteins. We purified an enzyme from the phalloidin-producing mushroom
      Conocybe albipes that cleaves a synthetic 22-mer phalloidin peptide to release
      the mature toxin peptide (AWLATCP). Mass spectrometric analysis of the purified
      protein combined with isolation and sequencing of the encoding gene indicates
      that the responsible processing enzyme is a member of the prolyl oligopeptidase
      (POP) subfamily of proteases (EC 3.4.21.26). The processing enzyme was able to
      use the chromogenic POP substrate benzyloxycarbonyl-Gly-Pro-p-nitroanilide and
      was inhibited by the specific POP inhibitor benzyloxycarbonyl-Pro-prolinal. Both
      Pro bonds in the proprotein are cleaved by the same enzyme, with the C-terminal
      Pro bond cleaved first or much faster than the N-terminal Pro bond. Transient
      accumulation of the N-terminal intermediate indicates that cleavage is not
      strongly processive. A synthetic peptide representing the phallacidin proprotein
      was also cleaved by the POP of C. albipes, but a precursor of amanitin (which is
      not made by C. albipes) was cleaved inefficiently.

PMID- 19389705
TI  - Biological activity of nerve growth factor precursor is dependent upon relative
      levels of its receptors.
AB  - Nerve growth factor (NGF) is produced as a precursor called pro-nerve growth
      factor (proNGF), which is secreted by many tissues and is the predominant form of
      NGF in the central nervous system. In Alzheimer disease brain, cholinergic
      neurons degenerate and can no longer transport NGF as efficiently, leading to an
      increase in untransported NGF in the target tissue. The protein that accumulates
      in the target tissue is proNGF, not the mature form. The role of this precursor
      is controversial, and both neurotrophic and apoptotic activities have been
      reported for recombinant proNGFs. Differences in the protein structures, protein
      expression systems, methods used for protein purification, and methods used for
      bioassay may affect the activity of these proteins. Here, we show that proNGF is
      neurotrophic regardless of mutations or tags, and no matter how it is purified or
      in which system it is expressed. However, although proNGF is neurotrophic under
      our assay conditions for primary sympathetic neurons and for pheochromocytoma
      (PC12) cells, it is apoptotic for unprimed PC12 cells when they are deprived of
      serum. The ratio of tropomyosin-related kinase A to p75 neurotrophin receptor is
      low in unprimed PC12 cells compared with primed PC12 cells and sympathetic
      neurons, altering the balance of proNGF-induced signaling to favor apoptosis. We
      conclude that the relative level of proNGF receptors determines whether this
      precursor exhibits neurotrophic or apoptotic activity.

PMID- 19389706
TI  - Protein kinase A-regulated assembly of a MEF2{middle dot}HDAC4 repressor complex
      controls c-Jun expression in vascular smooth muscle cells.
AB  - Vascular smooth muscle cells (VSMCs) maintain the ability to modulate their
      phenotype in response to changing environmental stimuli. This phenotype
      modulation plays a critical role in the development of most vascular disease
      states. In these studies, stimulation of cultured vascular smooth muscle cells
      with platelet-derived growth factor resulted in marked induction of c-jun
      expression, which was attenuated by protein kinase Cdelta and calcium/calmodulin
      dependent protein kinase inhibition. Given that these signaling pathways have
      been shown to relieve the repressive effects of class II histone deacetylases
      (HDACs) on myocyte enhancer factor (MEF) 2 proteins, we ectopically expressed
      HDAC4 and observed repression of c-jun expression. Congruently, suppression of
      HDAC4 by RNA interference resulted in enhanced c-jun expression. Consistent with
      these findings, mutation of the MEF2 cis-element in the c-jun promoter resulted
      in promoter activation during quiescent conditions, suggesting that the MEF2 cis
      element functions as a repressor in this context. Furthermore, we demonstrate
      that protein kinase A attenuates c-Jun expression by promoting the formation of a
      MEF2.HDAC4 repressor complex by inhibiting salt-inducible kinase 1. Finally, we
      document a physical interaction between c-Jun and myocardin, and we document that
      forced expression of c-Jun represses the ability of myocardin to activate smooth
      muscle gene expression. Thus, MEF2 and HDAC4 act to repress c-Jun expression in
      quiescent VSMCs, protein kinase A enhances this repression, and platelet-derived
      growth factor derepresses c-Jun expression through calcium/calmodulin-dependent
      protein kinases and novel protein kinase Cs. Regulation of this molecular
      "switch" on the c-jun promoter may thus prove critical for toggling between the
      activated and quiescent VSMC phenotypes.

PMID- 19389707
TI  - Host cell P-glycoprotein is essential for cholesterol uptake and replication of
      Toxoplasma gondii.
AB  - P-glycoprotein (P-gp) is a membrane-bound efflux pump that actively exports a
      wide range of compounds from the cell and is associated with the phenomenon of
      multidrug resistance. However, the role of P-gp in normal physiological processes
      remains elusive. Using P-gp-deficient fibroblasts, we showed that P-gp was
      critical for the replication of the intracellular parasite Toxoplasma gondii but
      was not involved in invasion of host cells by the parasite. Importantly, we found
      that the protein participated in the transport of host-derived cholesterol to the
      intracellular parasite. T. gondii replication in P-gp-deficient host cells not
      only resulted in reduced cholesterol content in the parasite but also altered its
      sphingolipid metabolism. In addition, we found that different levels of P-gp
      expression modified the cholesterol metabolism in uninfected fibroblasts.
      Collectively our findings reveal a key and previously undocumented role of P-gp
      in host-parasite interaction and suggest a physiological role for P-gp in
      cholesterol trafficking in mammalian cells.

PMID- 19389708
TI  - {alpha}MSH and Cyclic AMP elevating agents control melanosome pH through a
      protein kinase A-independent mechanism.
AB  - Melanins are synthesized in melanocytes within specialized organelles called
      melanosomes. Numerous studies have shown that the pH of melanosome plays a key
      role in the regulation of melanin synthesis. However, until now, acute regulation
      of melanosome pH by a physiological stimulus has never been demonstrated. In the
      present study, we show that the activation of the cAMP pathway by alphaMSH or
      forskolin leads to an alkalinization of melanosomes and a concomitant regulation
      of vacuolar ATPases and ion transporters of the solute carrier family. The solute
      carrier family members include SLC45A2, which is mutated in oculocutaneous
      albinism type IV, SLC24A4 and SLC24A5, proteins implicated in the control of eye,
      hair, and skin pigmentation, and the P protein, encoded by the oculocutaneous
      albinism type II locus. Interestingly, H89, a pharmacological inhibitor of
      protein kinase A (PKA), prevents the cAMP-induced pigmentation and induces
      acidification of melanosomes. The drastic depigmenting effect of H89 is not due
      to an inhibition of tyrosinase expression. Indeed, H89 blocks the induction of
      melanogenesis induced by LY294002, a potent inhibitor of the PI 3-kinase pathway,
      without any effect on tyrosinase expression. Furthermore, PKA is not involved in
      the inhibition of pigmentation promoted by H89 because LY294002 induces
      pigmentation independently of PKA. Also, other PKA inhibitors do not affect
      pigmentation. Taken together, our results strengthen the support for a key role
      of melanosome pH in the regulation of melanin synthesis and, for the first time,
      demonstrate that melanosome pH is regulated by cAMP and alphaMSH. Notably, these
      are both mediators of the response to solar UV radiation, the main physiological
      stimulus of skin pigmentation.

PMID- 19389709
TI  - Identification of a novel negative regulator of activin/nodal signaling in
      mesendodermal formation of Xenopus embryos.
AB  - Phosphotyrosine binding (PTB) domains, which are found in a large number of
      proteins, have been implicated in signal transduction mediated by growth factor
      receptors. However, the in vivo roles of these PTB-containing proteins remain to
      be investigated. Here, we show that Xdpcp (Xenopus dok-PTB containing protein)
      has a pivotal role in regulating mesendoderm formation in Xenopus, and negatively
      regulates the activin/nodal signaling pathway. We isolated cDNA for xdpcp and
      examined its potential role in Xenopus embryogenesis. We found that Xdpcp is
      strongly expressed in the animal hemisphere at the cleavage and blastula stages.
      The overexpression of xdpcp RNA affects activin/nodal signaling, which causes
      defects in mesendoderm formation. In addition, loss of Xdpcp function by
      injection of morpholino oligonucleotides leads to the expansion of the mesodermal
      territory. Moreover, we found that axis duplication by ventrally forced
      expression of activin is recovered by coexpression with Xdpcp. In addition, Xdpcp
      inhibits the phosphorylation and nuclear translocation of Smad2. Furthermore, we
      also found that Xdpcp interacts with Alk4, a type I activin receptor, and
      inhibits activin/nodal signaling by disturbing the interaction between Smad2 and
      Alk4. Taken together, these results indicate that Xdpcp regulates activin/nodal
      signaling that is essential for mesendoderm specification.

PMID- 19389710
TI  - Identification and functional characterization of protein kinase A-catalyzed
      phosphorylation of potassium channel Kv1.2 at serine 449.
AB  - Vascular smooth muscle Kv1 delayed rectifier K+ channels (KDR) containing Kv1.2
      control membrane potential and thereby regulate contractility. Vasodilatory
      agonists acting via protein kinase A (PKA) enhance vascule smooth muscle Kv1
      activity, but the molecular basis of this regulation is uncertain. We
      characterized the role of a C-terminal phosphorylation site, Ser-449, in Kv1.2
      expressed in HEK 293 cells by biochemical and electrophysiological methods. We
      found that 1) in vitro phosphorylation of Kv1.2 occurred exclusively at serine
      residues, 2) one major phosphopeptide that co-migrated with 449pSASTISK was
      generated by proteolysis of in vitro phosphorylated Kv1.2, 3) the peptide
      445KKSRSASTISK exhibited stoichiometric phosphorylation by PKA in vitro, 4)
      matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass
      spectroscopy (MS) and MS/MS confirmed in vitro Ser-449 phosphorylation by PKA, 5)
      in situ phosphorylation at Ser-449 was detected in HEK 293 cells by MALDI-TOF MS
      followed by MS/MS. MIDAS (multiple reaction monitoring-initiated detection and
      sequencing) analysis revealed additional phosphorylated residues, Ser-440 and Ser
      441, 6) in vitro 32P incorporation was significantly reduced in Kv1.2-S449A,
      Kv1.2-S449D, and Kv1.2-S440A/S441A/S449A mutant channels, but Kv1.2-S440A/S441A
      was identical to wild-type Kv1.2 (Kv1.2-WT), and 7) bath applied 8-Br-cAMP or
      dialysis with PKA catalytic subunit (cPKA) increased Kv1.2-WT but not Kv1.2-S449A
      current amplitude. cPKA increased Kv1.2-WT current in inside-out patches. Rp-CPT
      cAMPS reduced Kv1.2-WT current, blocked the increase due to 8-Br-cAMP, but had no
      effect on Kv1.2-S449A. cPKA increased current due to double mutant Kv1.2
      S440A/S441A but had no effect on Kv1.2-S449D or Kv1.2-S440A/S441A/S449A. We
      conclude that Ser-449 in Kv1.2 is a site of PKA phosphorylation and a potential
      molecular mechanism for Kv1-containing KDR channel modulation by agonists via PKA
      activation.

PMID- 19389711
TI  - The structure of the bacterial oxidoreductase enzyme DsbA in complex with a
      peptide reveals a basis for substrate specificity in the catalytic cycle of DsbA
      enzymes.
AB  - Oxidative protein folding in Gram-negative bacteria results in the formation of
      disulfide bonds between pairs of cysteine residues. This is a multistep process
      in which the dithiol-disulfide oxidoreductase enzyme, DsbA, plays a central role.
      The structure of DsbA comprises an all helical domain of unknown function and a
      thioredoxin domain, where active site cysteines shuttle between an oxidized,
      substrate-bound, reduced form and a DsbB-bound form, where DsbB is a membrane
      protein that reoxidizes DsbA. Most DsbA enzymes interact with a wide variety of
      reduced substrates and show little specificity. However, a number of DsbA enzymes
      have now been identified that have narrow substrate repertoires and appear to
      interact specifically with a smaller number of substrates. The transient nature
      of the DsbA-substrate complex has hampered our understanding of the factors that
      govern the interaction of DsbA enzymes with their substrates. Here we report the
      crystal structure of a complex between Escherichia coli DsbA and a peptide with a
      sequence derived from a substrate. The binding site identified in the DsbA
      peptide complex was distinct from that observed for DsbB in the DsbA-DsbB
      complex. The structure revealed details of the DsbA-peptide interaction and
      suggested a mechanism by which DsbA can simultaneously show broad specificity for
      substrates yet exhibit specificity for DsbB. This mode of binding was supported
      by solution nuclear magnetic resonance data as well as functional data, which
      demonstrated that the substrate specificity of DsbA could be modified via changes
      at the binding interface identified in the structure of the complex.

PMID- 19389713
TI  - Boropinic acid, a novel inhibitor of Helicobacter pylori stomach colonization.

PMID- 19389712
TI  - Adipose triglyceride lipase is implicated in fuel- and non-fuel-stimulated
      insulin secretion.
AB  - Reduced lipolysis in hormone-sensitive lipase-deficient mice is associated with
      impaired glucose-stimulated insulin secretion (GSIS), suggesting that endogenous
      beta-cell lipid stores provide signaling molecules for insulin release.
      Measurements of lipolysis and triglyceride (TG) lipase activity in islets from
      HSL(-/-) mice indicated the presence of other TG lipase(s) in the beta-cell.
      Using real time-quantitative PCR, adipose triglyceride lipase (ATGL) was found to
      be the most abundant TG lipase in rat islets and INS832/13 cells. To assess its
      role in insulin secretion, ATGL expression was decreased in INS832/13 cells (ATGL
      knockdown (KD)) by small hairpin RNA. ATGL-KD increased the esterification of
      free fatty acid (FFA) into TG. ATGL-KD cells showed decreased glucose- or Gln +
      Leu-induced insulin release, as well as reduced response to KCl or palmitate at
      high, but not low, glucose. The K(ATP)-independent/amplification pathway of GSIS
      was considerably reduced in ATGL-KD cells. ATGL(-/-) mice were hypoinsulinemic
      and hypoglycemic and showed decreased plasma TG and FFAs. A hyperglycemic clamp
      revealed increased insulin sensitivity and decreased GSIS and arginine-induced
      insulin secretion in ATGL(-/-) mice. Accordingly, isolated islets from ATGL(-/-)
      mice showed reduced insulin secretion in response to glucose, glucose +
      palmitate, and KCl. Islet TG content and FFA esterification into TG were
      increased by 2-fold in ATGL(-/-) islets, but glucose usage and oxidation were
      unaltered. The results demonstrate the importance of ATGL and intracellular lipid
      signaling for fuel- and non-fuel-induced insulin secretion.

PMID- 19389714
TI  - Comparison of the pharmacokinetics, safety and tolerability of daptomycin in
      healthy adult volunteers following intravenous administration by 30 min infusion
      or 2 min injection.
AB  - OBJECTIVES: Two randomized Phase I studies in separate populations of healthy
      adult volunteers investigated the pharmacokinetics, safety and tolerability of
      daptomycin (Cubicin; Novartis Pharma AG, Basel, Switzerland) administered as a 2
      min intravenous (iv) injection, relative to the currently licensed 30 min iv
      infusion. METHODS: Study 1 was an open-label, single-dose, two-period, crossover
      study in which each subject received 6 mg/kg daptomycin administered as a 30 min
      iv infusion (n = 15) and as a 2 min iv injection (n = 16). In Study 2, a single
      blind, multiple-dose, parallel-group study, subjects received a once-daily 2 min
      iv injection of 6 mg/kg daptomycin (n = 12), 4 mg/kg daptomycin (n = 8) or
      placebo (n = 4) for 7 days. Single-dose pharmacokinetics were assessed at various
      timepoints up to 36 and 24 h post-dose in Study 1 and Study 2, respectively, and
      multiple-dose pharmacokinetics were assessed in Study 2 at day 7 for 48 h post
      dose. RESULTS: In Study 1, pharmacokinetic comparability between the two
      administration regimens was demonstrated by meeting the bioequivalence criteria
      for the exposure parameters, AUC(0-t), AUC(0-infinity) and C(max). In Study 2,
      time-invariant pharmacokinetic properties as well as dose-proportional
      pharmacokinetics were demonstrated for the daptomycin 2 min iv injection regimen.
      In both studies, daptomycin was well tolerated and the majority of treatment
      emergent adverse events were of mild intensity and considered to be unrelated to
      daptomycin. CONCLUSIONS: The similar pharmacokinetic and safety profiles of the
      two administration regimens suggest that the 2 min iv injection may be a
      convenient treatment option for both patients and healthcare professionals.

PMID- 19389715
TI  - Population analysis of the pregnancy-related modifications in lopinavir
      pharmacokinetics and their possible consequences for dose adjustment.
AB  - OBJECTIVES: To investigate the possible necessity of an increase in lopinavir
      dose during pregnancy in order to achieve the concentrations previously defined
      as predictive of virological efficacy. PATIENTS AND METHODS: Lopinavir
      pharmacokinetics were investigated by a population approach performed on 145 HIV
      infected women, including 74 pregnant women. The final model was used to
      determine the probability of achievement of the target trough concentrations by
      Monte Carlo simulations. RESULTS: The typical population estimates (inter
      individual variability %) of apparent clearance (CL/F) and volume of distribution
      were 4.38 L/h (24%) and 58.4 L (59%), respectively. Pregnancy associated with a
      gestational age >15 weeks and delivery were found to increase lopinavir CL/F by
      39% and 58%, respectively. With the standard 400 mg twice-a-day regimen, the
      probability of reaching the 1 mg/L target trough concentration for protease
      inhibitor (PI)-naive patients was 99% and 96% for non-pregnant and pregnant
      women, respectively. An important decrease in the probability of achieving the
      5.7 mg/L target trough concentration for salvage therapy was observed for non
      pregnant women (55%), this decrease being even greater for pregnant women (21%).
      Raising the lopinavir dose to 600 mg twice daily increased these probabilities to
      87% and 53% for non-pregnant and pregnant women, respectively. CONCLUSIONS:
      Modification of the lopinavir dose is unlikely to be required for PI-naive
      pregnant women; however, in pregnant women who have previously received a PI,
      therapeutic drug monitoring and/or empirical increasing of the dose should be
      considered.

PMID- 19389716
TI  - Follow-up standards and treatment targets in rheumatoid arthritis: results of a
      questionnaire at the EULAR 2008.
AB  - BACKGROUND: Therapeutic approaches to rheumatoid arthritis (RA) have undergone
      significant changes. The importance of tight control and early treatment, rapidly
      altered if goals are not achieved, is supported by evidence. However, it is
      unknown to what extent these insights are accepted by practitioners in clinical
      practice. OBJECTIVE: To obtain information about standard follow-up and treatment
      practices, and rheumatologists' aims in the care of patients with RA. METHODS: A
      survey conducted at the 2008 EULAR Congress. RESULTS: Most specialists, who were
      mainly from Europe and Latin America, were well-informed about recent concepts:
      two-thirds specified remission as a major goal. The experts attempted to reach
      treatment aims within 12-14 weeks, altering treatment otherwise. Disease activity
      assessment by composite measures is performed by a majority, although one-third
      preferentially relied upon their judgment. CONCLUSION: These results suggest the
      acceptance of ambitious treatment concepts in practice. Although voluntary
      surveys have limitations, the answers reflect widespread adoption of desirable
      standards of care.

PMID- 19389718
TI  - Pre- and postoperative fMRI and clinical memory performance in temporal lobe
      epilepsy.
AB  - OBJECTIVE: The present study aimed to examine and compare memory processing in
      patients with unilateral temporal lobe epilepsy (TLE) before and after surgery
      using functional magnetic resonance imaging (fMRI). METHODS: Seventeen
      preoperative patients with unilateral TLE (nine left, eight right) and eight
      healthy controls were recruited. They performed a complex visual scene-encoding
      task during fMRI to measure memory activation in the mesial temporal lobe. Their
      memory performance was evaluated using standardised neuropsychological tests.
      After unilateral temporal lobe resection (either temporal lobectomy, selective
      amygdalohippocampectomy or lesionectomy), the same fMRI paradigm and
      neuropsychological tests were administered to the patient group. RESULTS: Left
      TLE patients demonstrated a decline in verbal memory after left temporal lobe
      resection. Their postoperative verbal and visual memory performance was
      positively associated with postoperative functional activation in the right
      mesial temporal lobe, whereas the postoperative memory performance of right-TLE
      patients was positively associated with postoperative functional activation in
      the left mesial temporal lobe, contralateral to their respective side of
      resection. CONCLUSION: Postoperative memory performance was significantly
      associated with functional activation contralateral to the side of resection in
      patients with unilateral TLE, and the function of the contralateral mesial
      temporal lobe might play an important role in supporting memory performance after
      temporal lobe resection.

PMID- 19389717
TI  - Selection and characterization of DARPins specific for the neurotensin receptor
      1.
AB  - We describe here the selection and characterization of designed ankyrin repeat
      proteins (DARPins) that bind specifically to the rat neurotensin receptor 1
      (NTR1), a G-protein coupled receptor (GPCR). The selection procedure using
      ribosome display and the initial clone analysis required <10 microg of detergent
      solubilized, purified NTR1. Complex formation with solubilized GPCR was
      demonstrated by ELISA and size-exclusion chromatography; additionally, the GPCR
      could be detected in native membranes of mammalian cells using fluorescence
      microscopy. The main binding epitope in the GPCR lies within the 33 amino acids
      following the seventh transmembrane segment, which comprise the putative helix 8,
      and additional binding interactions are possibly contributed by the cytoplasmic
      loop 3, thus constituting a discontinuous epitope. Since the selected binders
      recognize the GPCR both in detergent-solubilized and in membrane-embedded forms,
      they will be potentially useful both in co-crystallization trials and for signal
      transduction experiments.

PMID- 19389719
TI  - Clinical characteristics of patients with obstructive coronary lesions in the
      absence of coronary calcification: an evaluation by coronary CT angiography.
AB  - BACKGROUND: Multidetector CT allows detection of coronary artery calcium and,
      after contrast injection, visualisation of the coronary artery lumen. It is
      commonly assumed that the absence of coronary calcification makes the presence of
      obstructive coronary lesions highly unlikely. This study evaluates the clinical
      characteristics of patients with at least one symptomatic, high-grade coronary
      artery stenosis in both computed tomography and invasive angiography but absence
      of any coronary calcification and compares the results with patients with
      stenoses in the setting of detectable coronary calcium PATIENTS AND METHODS: The
      study retrospectively identified 21 consecutive patients with symptoms in whom a
      high-grade coronary artery stenosis had been identified in 64-slice or dual
      source CT coronary angiography (Siemens Sensation 64 or Siemens Definition, 120
      kV, 50 to 85 ml of intravenous contrast at 5 ml/s) in the absence of coronary
      calcium and in whom that finding had been confirmed by invasive coronary
      angiography. Clinical presentation ("unstable": all forms of acute coronary
      syndrome versus "stable": stable chest pain or dyspnoea on exertion) and standard
      cardiovascular risk factors were assessed, and the results were compared with 42
      consecutive patients with symptoms in whom both coronary calcium and coronary
      stenoses had been identified in computed tomography and invasive coronary
      angiography. RESULTS: The majority of patients with coronary stenoses in the
      absence of coronary calcium presented with "unstable" symptoms (non-ST-segment
      elevation myocardial infarction (NSTEMI) or unstable angina), significantly more
      frequently than patients with detectable calcification (71% vs 26%, p = 0.001).
      The age range of patients without calcium was 33 to 76 years, their mean age was
      younger (53 (SD 13) vs 63 (8) years, p<0.001), but none of the risk factors
      showed any significant difference compared with patients with calcification.
      CONCLUSION: The presence of significant coronary artery stenosis in the absence
      of coronary calcium is possible. It is more likely in the setting of unstable
      angina or NSTEMI than in stable chest pain and occurs more frequently in younger
      patients.

PMID- 19389720
TI  - Cardiorespiratory risk factors as predictors of 40-year mortality in women and
      men.
AB  - OBJECTIVE: Most historical studies of cardiorespiratory risk factors as
      predictors of mortality have been based on men. This study examines whether they
      predict mortality over long periods in women and men. DESIGN: Prospective cohort
      study. SETTING: Participants were employees of the General Post Office. METHODS:
      Risk factor data were collected via clinical examination and questionnaire, 1966
      7. Associations between cardiorespiratory risk factors and 40-year mortality were
      determined for 644 women and 1272 men aged 35-70 at examination. MAIN OUTCOME
      MEASURES: All-cause, cardiovascular (CVD), cancer and respiratory mortality.
      RESULTS: Associations between systolic blood pressure and all-cause and stroke
      mortality were equally strong for women and men, hazard ratio (95% confidence
      interval) 1.25 (1.1 to 1.4) and 1.18 (1.1 to 1.3); and 2.17 (1.7 to 2.8) and 1.69
      (1.4 to 2.1), respectively. Cholesterol was higher in women and was associated
      with all-cause 1.22 (1.1 to 1.4) and CVD 1.39 (1.2 to 1.7) mortality, while
      associations between 2-hour glucose and all-cause 1.15 (1.1 to 1.2), coronary
      heart disease (CHD) 1.25 (1.1 to 1.4) and respiratory mortality 1.21 (1.0 to 1.5)
      were observed in men. Obesity was associated with stroke in women (2.42 (1.12 to
      5.24)) and CHD in men (1.59 (1.02 to 2.49)), while ECG ischaemia was associated
      with CVD in both sexes. The strongest, most consistent predictor of mortality was
      smoking in women and poor lung function in men. However, evidence of sex
      differences in associations between the cardiorespiratory risk factors measured
      and mortality was sparse. CONCLUSIONS: Data from a 40-year follow-up period show
      remarkably persistent associations between risk factors and cardiorespiratory and
      all-cause mortality in women and men.

PMID- 19389721
TI  - Lesions without calcium: lessons from CT angiography.

PMID- 19389722
TI  - Energetic state is a strong regulator of sarcoplasmic reticulum Ca2+ loss in
      cardiac muscle: different efficiencies of different energy sources.
AB  - AIMS: Increased diastolic sarcoplasmic reticulum (SR) Ca(2+) loss could depress
      contractility in heart failure. Since the failing myocardium has impaired
      energetics, we investigated whether Ca(2+) loss is linked to changes in energetic
      pathways. METHODS AND RESULTS: Leakage from SR in mouse permeabilized
      preparations was assessed using exogenous ATP, ATP + phosphocreatine (activation
      of bound creatine kinase, CK), ATP + mitochondrial substrates (mitochondrial
      activation), or with all of these together (optimal energetic conditions) in
      Ca(2+)-free solution. In ventricular fibres caffeine-induced tension transients
      under optimal energetic conditions were used to estimate SR [Ca(2+)]. In
      cardiomyocytes, intra-SR Ca(2+) was monitored by use of the fluorescent marker
      Mag-fluo 4. In fibres, SR Ca(2+) content after 5 min incubation strongly depended
      on energy supply (100%-optimal energetic conditions; 27 +/- 5%-exogenous ATP
      only, 52 +/- 5%-endogenous CK activation; 88 +/- 8%-mitochondrial activation, P <
      0.01 vs. CK system). The significant loss with only exogenous ATP was not
      inhibited by the ryanodine receptor blockers tetracaine or ruthenium red.
      However, the SR Ca(2+)-ATPase (SERCA) inhibitors cyclopiazonic acid or 2,5
      di(tert-butyl)-1,4-benzohydroquinone significantly decreased Ca(2+) loss. At 100
      nM external [Ca(2+)], the SR Ca(2+) loss was also energy dependent and was not
      significantly inhibited by tetracaine. In cardiomyocytes, the decline in SR
      [Ca(2+)] at zero external [Ca(2+)] was almost two times slower under optimal
      energetic conditions than in the presence of exogenous ATP only. CONCLUSION: At
      low extra-reticular [Ca(2+)], the main leak pathway is an energy-sensitive
      backward Ca(2+) pump, and direct mitochondrial-SERCA ATP channelling is more
      effective in leak prevention than local ATP generation by bound CK.

PMID- 19389723
TI  - Combined reduction of intercellular coupling and membrane excitability
      differentially affects transverse and longitudinal cardiac conduction.
AB  - AIMS: Reduced excitability and gap junction expression are commonly found in
      electrically remodelled diseased hearts, but their contribution to slow
      conduction and arrhythmias is unclear. In this study, we have investigated the
      effect of isolated and combined reductions in membrane excitability and
      intercellular coupling on impulse propagation and arrhythmogeneity in genetically
      modified mice. METHODS AND RESULTS: Cx43 and Scn5a(1798insD/+) heterozygous (HZ)
      mice were crossbred to create a mixed offspring: wild-type (WT, n = 15), Cx43 HZ
      (n = 14), Scn5a(1798insD/+) (Scn5a) HZ (n = 17), and Cx43/Scn5a(1798insD/+)
      (Cx43/Scn5a) HZ (n = 15) mice. After ECG recording, epicardial activation mapping
      (208 recording sites) was performed on Langendorff-perfused hearts. Arrhythmia
      inducibility was tested by one to three premature stimuli and burst pacing.
      Conduction velocity longitudinal (CV(L)) and transverse (CV(T)) to fibre
      orientation and dispersion of conduction were determined during S1-S1 pacing (150
      ms). Connexin43 (Cx43) and sodium channel Nav1.5 protein expression and
      myocardial tissue collagen content were determined by immunohistology. Compared
      with WT animals, P, QRS, and QTc intervals were prolonged in Scn5a HZ and
      Cx43/Scn5a HZ, but not in Cx43 HZ animals. Scn5a HZ mice showed decreased CV(L)
      in right ventricle (RV) but not in left ventricle compared with WT. In the RV of
      Cx43/Scn5a HZ, CV(T) was reduced, but CV(L) was not different from WT. Arrhythmia
      inducibility was low and not increased in either single- or double-mutant mice.
      CONCLUSION: Reduction of both electrical coupling and excitability results in
      normal conduction velocity parallel to fibre orientation but in pronounced
      conduction slowing transverse to fibre orientation in RV only, although this does
      not affect arrhythmogeneity.

PMID- 19389724
TI  - Professional commitment to changing chronic illness care: results from disease
      management programmes.
AB  - OBJECTIVE: The aim of this exploratory study was to investigate to what extent
      primary care professionals are able to change their systems for delivering care
      to chronic obstructive pulmonary disease (COPD) patients and what professional
      and organizational factors are associated with the degree of process
      implementation. DESIGN: Quasi-experimental design with 1 year follow-up after
      intervention. SETTING: Three regional COPD management programmes in the
      Netherlands, in which general practices cooperated with regional hospitals.
      PARTICIPANTS: All participating primary care professionals (n = 52).
      INTERVENTION: COPD management programme. MAIN OUTCOME MEASURES: Professional
      commitment, organizational context and degree of process implementation. RESULTS:
      Professionals significantly changed their systems for delivering care to COPD
      patients, namely self-management support, decision support, delivery system
      design and clinical information systems. Associations were found between
      organizational factors, professional commitment and changes in processes of care.
      Group culture and professional commitment appeared to be, to a moderate degree,
      predictors of process implementation. CONCLUSIONS: COPD management was effective;
      all processes improved significantly. Moreover, theoretically expected
      associations between organizational context and professional factors with the
      implementation of COPD management were indeed confirmed to some extent. Group
      culture and professional commitment are important facilitators.

PMID- 19389725
TI  - Assessment of the optimization of affinity and specificity at protein-DNA
      interfaces.
AB  - The biological functions of DNA-binding proteins often require that they interact
      with their targets with high affinity and/or high specificity. Here, we describe
      a computational method that estimates the extent of optimization for affinity and
      specificity of amino acids at a protein-DNA interface based on the crystal
      structure of the complex, by modeling the changes in binding-free energy
      associated with all individual amino acid and base substitutions at the
      interface. The extent to which residues are predicted to be optimal for
      specificity versus affinity varies within a given protein-DNA interface and
      between different complexes, and in many cases recapitulates previous
      experimental observations. The approach provides a complement to traditional
      methods of mutational analysis, and should be useful for rapidly formulating
      hypotheses about the roles of amino acid residues in protein-DNA interfaces.

PMID- 19389726
TI  - ANNIE: integrated de novo protein sequence annotation.
AB  - Function prediction of proteins with computational sequence analysis requires the
      use of dozens of prediction tools with a bewildering range of input and output
      formats. Each of these tools focuses on a narrow aspect and researchers are
      having difficulty obtaining an integrated picture. ANNIE is the result of years
      of close interaction between computational biologists and computer scientists and
      automates an essential part of this sequence analytic process. It brings together
      over 20 function prediction algorithms that have proven sufficiently reliable and
      indispensable in daily sequence analytic work and are meant to give scientists a
      quick overview of possible functional assignments of sequence segments in the
      query proteins. The results are displayed in an integrated manner using an
      innovative AJAX-based sequence viewer. ANNIE is available online at:
      http://annie.bii.a-star.edu.sg. This website is free and open to all users and
      there is no login requirement.

PMID- 19389727
TI  - Medical and dental care utilization and expenditures under Medicaid and private
      health insurance.
AB  - Data from the 2005 Medical Expenditure Panel Survey were used to conduct a
      disaggregated comparison of utilization and expenditures under Medicaid and
      private health insurance for low-income adults and children. After adjustment for
      health status and other factors, Medicaid adults and children had greater use of
      prescription drugs than the privately insured, but there were no significant
      differences in prescription expenditures. Adults on Medicaid had lower
      utilization of office-based medical and dental care and much lower expenditures
      than the privately insured. Contrary to stereotypes, there were no significant
      differences between Medicaid adults and children and the privately insured in
      emergency, outpatient, or inpatient hospital use, and the former had
      significantly lower expenditures.

PMID- 19389729
TI  - NICE public health guidance: what's new?

PMID- 19389730
TI  - Literature-based priors for gene regulatory networks.
AB  - MOTIVATION: The use of prior knowledge to improve gene regulatory network
      modelling has often been proposed. In this article we present the first research
      on the massive incorporation of prior knowledge from literature for Bayesian
      network learning of gene networks. As the publication rate of scientific papers
      grows, updating online databases, which have been proposed as potential prior
      knowledge in past research, becomes increasingly challenging. The novelty of our
      approach lies in the use of gene-pair association scores that describe the
      overlap in the contexts in which the genes are mentioned, generated from a large
      database of scientific literature, harnessing the information contained in a huge
      number of documents into a simple, clear format. RESULTS: We present a method to
      transform such literature-based gene association scores to network prior
      probabilities, and apply it to learn gene sub-networks for yeast, Escherichia
      coli and Human organisms. We also investigate the effect of weighting the
      influence of the prior knowledge. Our findings show that literature-based priors
      can improve both the number of true regulatory interactions present in the
      network and the accuracy of expression value prediction on genes, in comparison
      to a network learnt solely from expression data. Networks learnt with priors also
      show an improved biological interpretation, with identified subnetworks that
      coincide with known biological pathways.

PMID- 19389728
TI  - Thrombin and interleukin-1beta decrease HOX gene expression in human first
      trimester decidual cells: implications for pregnancy loss.
AB  - Bleeding or inflammation in early pregnancy may result in pregnancy loss or
      defective implantation. Their effect on HOX gene expression in first trimester
      decidua is unknown. Bleeding results in thrombin generation, although infection
      or inflammation results in production of cytokines typified by Interleukin-1beta
      (IL-1beta). First trimester decidual cells were pretreated with 17beta estradiol
      (E(2)), medroxyprogesterone acetate (MPA) or both and subsequently treated with
      thrombin or IL-1beta. Affymetrix microarray analysis was used to assess the
      expression of all HOX genes and confirmed using real-time RT-PCR. E(2) or MPA
      treatment resulted in significant increases in HOXA10 and HOXA11. Subsequent
      treatment with thrombin resulted in diminished expression of HOXA10 and HOXA9.
      Treatment with IL-1beta resulted in decreased expression of HOXA1, 3, 9, 10 and
      11. HOXA10 expression was reduced by 70% after thrombin treatment (P = 0.018) and
      by 90% after IL-1beta treatment (P = 0.004). HOXA11 mRNA expression was decreased
      by 88% after IL-1beta treatment (P < 0.001), but not by thrombin treatment.
      Decidua was collected at the time of elective termination of pregnancy (n = 10)
      or surgical treatment of spontaneous pregnancy loss (n = 10). Real-time PCR and
      western analysis demonstrated decreased HOXA10 and HOXA11 RNA and protein
      expression in the decidua of spontaneous pregnancy loss compared with that of
      viable pregnancies. In conclusion, multiple HOX genes are expressed in decidual
      cells and inhibited by thrombin and IL-1beta. Since HOXA10 and HOXA11 are known
      to be necessary for successful pregnancy, these findings suggest a molecular
      mechanism by which bleeding or inflammation may affect pregnancy outcome.

PMID- 19389731
TI  - Augmented training of hidden Markov models to recognize remote homologs via
      simulated evolution.
AB  - MOTIVATION: While profile hidden Markov models (HMMs) are successful and powerful
      methods to recognize homologous proteins, they can break down when homology
      becomes too distant due to lack of sufficient training data. We show that we can
      improve the performance of HMMs in this domain by using a simple simulated model
      of evolution to create an augmented training set. RESULTS: We show, in two
      different remote protein homolog tasks, that HMMs whose training is augmented
      with simulated evolution outperform HMMs trained only on real data. We find that
      a mutation rate between 15 and 20% performs best for recognizing G-protein
      coupled receptor proteins in different classes, and for recognizing SCOP super
      family proteins from different families.

PMID- 19389732
TI  - KIRMES: kernel-based identification of regulatory modules in euchromatic
      sequences.
AB  - MOTIVATION: Understanding transcriptional regulation is one of the main
      challenges in computational biology. An important problem is the identification
      of transcription factor (TF) binding sites in promoter regions of potential TF
      target genes. It is typically approached by position weight matrix-based motif
      identification algorithms using Gibbs sampling, or heuristics to extend seed
      oligos. Such algorithms succeed in identifying single, relatively well-conserved
      binding sites, but tend to fail when it comes to the identification of
      combinations of several degenerate binding sites, as those often found in cis
      regulatory modules. RESULTS: We propose a new algorithm that combines the
      benefits of existing motif finding with the ones of support vector machines
      (SVMs) to find degenerate motifs in order to improve the modeling of regulatory
      modules. In experiments on microarray data from Arabidopsis thaliana, we were
      able to show that the newly developed strategy significantly improves the
      recognition of TF targets. AVAILABILITY: The python source code (open source
      licensed under GPL), the data for the experiments and a Galaxy-based web service
      are available at http://www.fml.mpg.de/raetsch/suppl/kirmes/.

PMID- 19389733
TI  - Protein function annotation from sequence: prediction of residues interacting
      with RNA.
AB  - MOTIVATION: All eukaryotic proteomes are characterized by a significant
      percentage of proteins of unknown function. Comp-utational function prediction
      methods are therefore essential as initial steps in the function annotation
      process. This article describes an annotation method (PiRaNhA) for the prediction
      of RNA-binding residues (RBRs) from protein sequence information. A series of
      sequence properties (position specific scoring matrices, interface propensities,
      predicted accessibility and hydrophobicity) are used to train a support vector
      machine. This method is then evaluated for its potential to be applied to RNA
      binding function prediction at the level of the complete protein. RESULTS: The 5
      fold cross-validation of PiRaNhA on a dataset of 81 RNA-binding proteins achieves
      a Matthews Correlation Coefficient (MCC) of 0.50 and accuracy of 87.2%. When used
      to predict RBRs in 42 proteins not used in training, PiRaNhA achieves an MCC of
      0.41 and accuracy of 84.5%. Decision values from the PiRaNhA predictions were
      used in a second SVM to make predictions of RNA-binding function at the protein
      level, achieving an MCC of 0.53 and accuracy of 76.1%. The PiRaNhA RBR
      predictions allow experimentalists to perform more targeted experiments for
      function annotation; and the prediction of RNA-binding function at the protein
      level shows promise for proteome-wide annotations. AVAILABILITY AND
      IMPLEMENTATION: Freely available on the web at
      www.bioinformatics.sussex.ac.uk/PIRANHA or http://piranha.protein.osaka-u.ac.jp.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at the Bioinformatics
      online.

PMID- 19389734
TI  - MetaTISA: Metagenomic Translation Initiation Site Annotator for improving gene
      start prediction.
AB  - SUMMARY: We proposed a tool named MetaTISA with an aim to improve TIS prediction
      of current gene-finders for metagenomes. The method employs a two-step strategy
      to predict translation initiation sites (TISs) by first clustering metagenomic
      fragments into phylogenetic groups and then predicting TISs independently for
      each group in an unsupervised manner. As evaluated on experimentally verified
      TISs, MetaTISA greatly improves the accuracies of TIS prediction of current gene
      finders. AVAILABILITY: The C++ source code is freely available under the GNU GPL
      license via http://mech.ctb.pku.edu.cn/MetaTISA/.

PMID- 19389735
TI  - A Bayesian segmentation approach to ascertain copy number variations at the
      population level.
AB  - MOTIVATION: Efficient and accurate ascertainment of copy number variations (CNVs)
      at the population level is essential to understand the evolutionary process and
      population genetics, and to apply CNVs in population-based genome-wide
      association studies for complex human diseases. We propose a novel Bayesian
      segmentation approach to identify CNVs in a defined population of any size. It is
      computationally efficient and provides statistical evidence for the detected CNVs
      through the Bayes factor. This approach has the unique feature of carrying out
      segmentation and assigning copy number status simultaneously-a desirable property
      that current segmentation methods do not share. RESULTS: In comparisons with
      popular two-step segmentation methods for a single individual using benchmark
      simulation studies, we find the new approach to perform competitively with
      respect to false discovery rate and sensitivity in breakpoint detection. In a
      simulation study of multiple samples with recurrent copy numbers, the new
      approach outperforms two leading single sample methods. We further demonstrate
      the effectiveness of our approach in population-level analysis of previously
      published HapMap data. We also apply our approach in studying population genetics
      of CNVs. AVAILABILITY: R programs are available at
      http://www.mshri.on.ca/mitacs/software/SOFTWARE.HTML

PMID- 19389736
TI  - A practical algorithm for finding maximal exact matches in large sequence
      datasets using sparse suffix arrays.
AB  - MOTIVATION: High-throughput sequencing technologies place ever increasing demands
      on existing algorithms for sequence analysis. Algorithms for computing maximal
      exact matches (MEMs) between sequences appear in two contexts where high
      throughput sequencing will vastly increase the volume of sequence data: (i)
      seeding alignments of high-throughput reads for genome assembly and (ii)
      designating anchor points for genome-genome comparisons. RESULTS: We introduce a
      new algorithm for finding MEMs. The algorithm leverages a sparse suffix array
      (SA), a text index that stores every K-th position of the text. In contrast to a
      full text index that stores every position of the text, a sparse SA occupies much
      less memory. Even though we use a sparse index, the output of our algorithm is
      the same as a full text index algorithm as long as the space between the indexed
      suffixes is not greater than a minimum length of a MEM. By relying on partial
      matches and additional text scanning between indexed positions, the algorithm
      trades memory for extra computation. The reduced memory usage makes it possible
      to determine MEMs between significantly longer sequences. AVAILABILITY: Source
      code for the algorithm is available under a BSD open source license at
      http://compbio.cs.princeton.edu/mems. The implementation can serve as a drop-in
      replacement for the MEMs algorithm in MUMmer 3.

PMID- 19389737
TI  - CROC: finding chromosomal clusters in eukaryotic genomes.
AB  - SUMMARY: There is increasing evidence showing that co-expression of genes that
      cluster along the genome is a common characteristic of eukaryotic transcriptomes.
      Several algorithms have been used to date in the identification of these kinds of
      gene organization. Here, we present a web tool called CROC that aims to help in
      the identification and analysis of genomic gene clusters. This method has been
      successfully used before in the identification of chromosomal clusters in
      different eukaryotic species. AVAILABILITY: The web server is freely available to
      non-commercial users at the following address: http://metagenomics.uv.es/CROC/.

PMID- 19389738
TI  - Systematic analysis of synchronized oscillatory neuronal networks reveals an
      enrichment for coupled direct and indirect feedback motifs.
AB  - MOTIVATION: Synchronized bursting behavior is a remarkable phenomenon in neural
      dynamics. So, identification of the underlying functional structure is crucial to
      understand its regulatory mechanism at a system level. On the other hand, we
      noted that feedback loops (FBLs) are commonly used basic building blocks in
      engineering circuit design, especially for synchronization, and they have also
      been considered as important regulatory network motifs in systems biology. From
      these motivations, we have investigated the relationship between synchronized
      bursting behavior and feedback motifs in neural networks. RESULTS: Through
      extensive simulations of synthetic spike oscillation models, we found that a
      particular structure of FBLs, coupled direct and indirect positive feedback loops
      (PFLs), can induce robust synchronized bursting behaviors. To further investigate
      this, we have developed a novel FBL identification method based on sampled time
      series data and applied it to synchronized spiking records measured from cultured
      neural networks of rat by using multi-electrode array. As a result, we have
      identified coupled direct and indirect PFLs. CONCLUSION: We therefore conclude
      that coupled direct and indirect PFLs might be an important design principle that
      causes the synchronized bursting behavior in neuronal networks although an
      extrapolation of this result to in vivo brain dynamics still remains an
      unanswered question.

PMID- 19389739
TI  - The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking
      and potential drug targets.
AB  - The search for the underlying mechanism through which insulin regulates glucose
      uptake into peripheral tissues has unveiled a highly intricate network of
      molecules that function in concert to elicit the redistribution or
      'translocation' of the glucose transporter isoform GLUT4 from intracellular
      membranes to the cell surface. Following recent technological advances within
      this field, this review aims to bring together the key molecular players that are
      thought to be involved in GLUT4 translocation and will attempt to address the
      spatial relationship between the signalling and trafficking components of this
      event. We will also explore the degree to which components of the insulin
      signalling and GLUT4 trafficking machinery may serve as potential targets for the
      development of orally available insulin mimics for the treatment of diabetes
      mellitus.

PMID- 19389740
TI  - Betting on health.

PMID- 19389741
TI  - A quarter of stroke patients are still not treated in a stroke unit.

PMID- 19389742
TI  - Sri Lanka's medical facilities overwhelmed by large influx of wounded.

PMID- 19389743
TI  - Tai Chi Qigong for the quality of life of patients with knee osteoarthritis: a
      pilot, randomized, waiting list controlled trial.
AB  - OBJECTIVE: To evaluate the effects of Tai Chi Qigong training on the quality of
      life and physical function of patients with osteoarthritis of the knee. DESIGN: A
      preliminary, single-blind, randomized controlled trial. SETTING: General
      community, performed at Hwaseong City Health Center. PARTICIPANTS: Forty-four
      elderly subjects (mean age, 69.1 +/- 5.4 years) with knee osteoarthritis.
      INTERVENTION: The patients were randomized (2:1) to: (1) an eight-week Tai Chi
      Qigong training programme or (2) a waiting list control group. The programme
      involved eight weeks of group Tai Chi Qigong sessions, with 60 minutes per
      session twice a week. MAIN OUTCOME MEASURES: The primary outcome was quality of
      life measured with the Short Form 36 (SF-36) at baseline and week 8. Secondary
      outcomes included the Western Ontario and McMaster University Osteoarthritis
      Index (WOMAC) and 6-m walking time. RESULTS: The training group had statistically
      significant improvements in the quality of life (changes of SF-36, Qigong versus
      control: 21.6 +/- 16.8 versus 9.8 +/- 13.6, P < 0.05) and 6-m walking test
      (change in walking time, Qigong versus control: -1.6 +/- 1.7 versus -0.2 +/- 0.8
      s, P < 0.01). The WOMAC scores in the training group were markedly improved,
      although the differences were not statistically significant. CONCLUSIONS: Tai Chi
      Qigong training appears to have beneficial effects in terms of the quality of
      life and physical functioning of elderly subjects with knee osteoarthritis.
      However, more rigorous trials are needed to confirm the efficacy of this training
      for patients with osteoarthritis of the knee.

PMID- 19389744
TI  - Safety of botulinum toxin type A among children with spasticity secondary to
      cerebral palsy: a systematic review of randomized clinical trials.
AB  - OBJECTIVE: To assess the safety of botulinum toxin type A for children with
      cerebral palsy using data from randomized clinical trials. DATA SOURCES: A search
      was conducted of MEDLINE database for the period January 1990 to February 2008. A
      complementary search was carried out of references from previous reviews. From
      122 articles, 20 randomized clinical trials were selected for the review. REVIEW
      METHODS: Two authors independently assessed eligibility of the studies and
      methodological quality of those according to CONSORT guidelines. For each adverse
      effect, relative risk was calculated, and when more than one study reported
      adverse effects, a meta-analysis was carried out. Sensitivity analyses with
      different continuity corrections factors were performed when zero cases were
      reported in a study arm. RESULTS: There were 882 participants in the 20 studies
      included in the meta-analysis. Six studies reported zero adverse effects. Thirty
      five different adverse events were reported. Botulinum toxin type A use was
      related to respiratory tract infection, bronchitis, pharyngytis, asthma, muscle
      weakness, urinary incontinence, falls, seizures, fever and unspecified pain. Two
      deaths were reported in the study with higher person-time follow-up (relative
      risk (RR) 4.69, 95% confidence interval (CI) 0.23-95). CONCLUSIONS: Botulinum
      toxin type A has a good safety profile during the first months of use. However
      the occurrence of adverse events is more frequent among children with cerebral
      palsy than individuals with other conditions. Severe adverse events are
      potentially related with the use of botulinum toxin type A, but data are sparse
      and additional study is required to clarify the causal relation.

PMID- 19389745
TI  - A clinical practice guideline for physiotherapists treating patients with chronic
      obstructive pulmonary disease based on a systematic review of available evidence.
AB  - PURPOSE: Update of a clinical practice guideline for the physiotherapy management
      of patients with chronic obstructive pulmonary disease supporting the clinical
      decision-making process. METHODS: A systematic computerized literature search was
      performed on different modalities for improving physical exercise capacity,
      reducing exertional dyspnoea, improving airway clearance and encouraging changes
      in physical activity behaviour. Methodological quality was scored with the PEDro
      Scale. Scientific conclusions were graded according to the criteria of the; Dutch
      Evidence Based Guideline Development Platform'. These, together with practical
      considerations, were used to formulate recommendations for clinical practice.
      RESULTS: A total of 103 studies were included in the systematic review,
      consisting of five meta-analyses of randomized controlled trials, 84 randomized
      controlled trials and 14 uncontrolled studies. Twenty scientific conclusions
      supported six recommendations on physical exercise training. Nineteen scientific
      conclusions supported eight recommendations on interventions for reducing
      dyspnoea. Five scientific conclusions supported seven recommendations concerning
      treatment modalities to improve mucus clearance, and two scientific conclusions
      supported two recommendations on strategies for encouraging permanent changes in
      physical activity behaviour. CONCLUSIONS: Strong recommendations support the use
      of physical exercise training to improve health-related quality of life and
      functional exercise capacity. Future research should investigate whether
      additional interventions for reducing exertional dyspnoea have a place as
      adjuncts to physical exercise training in selected patients. In addition,
      treatment of impaired mucus clearance, especially during acute exacerbations,
      requires further research. With the advance of new technologies for objective
      measurements of physical activities in daily life more research is needed
      concerning interventions to initiate and maintain physical activity behaviour
      change during and after supervised physical exercise training programmes.

PMID- 19389746
TI  - A computerized visual perception rehabilitation programme with interactive
      computer interface using motion tracking technology -- a randomized controlled,
      single-blinded, pilot clinical trial study.
AB  - OBJECTIVE: To assess the effectiveness of a computerized visual perception
      rehabilitation programme using motion tracking technology for visual perception
      impairment. DESIGN: Randomized controlled, single-blinded, pilot clinical trial
      study. SETTING: Inpatient rehabilitation hospital. SUBJECTS: Sixteen left
      hemiplegic patients with visual perceptional impairment. INTERVENTION: Subjects
      were randomly assigned to receive either (1) participation in a computerized
      visual perception rehabilitation programme with an interactive patient-computer
      interface applying motion tracking technology based on the CAMSHIFT algorithm or
      (2) use of the PSS CogRehab program for three sessions per week, 30 minutes per
      session for four weeks. There were eight patients in each group. MAIN MEASURES:
      Mini-Mental Status Examination, Motor-free Visual Perception Test and Modified
      Barthel Index were assessed at the beginning and end of the training. A survey
      was conducted to evaluate the degree of patients' interest using an interest
      scale. RESULTS: After training, the mean (SD) Motor-free Visual Perception Test
      score increased significantly in both experimental group (from 65.8 (19.5) to
      77.8 (28.7)) and control group (from 68.3 (11.4) to 74.1 (14.8)) (P<0.01).
      Modified Barthel Index score increased significantly in both groups, with the
      experimental group recording a higher increase. Mean (SD) interest scale score
      was greater in the experimental group (2.2 (0.8)) than in the control group (1.3
      (0.7)) (P<0.01). CONCLUSIONS: A computerized visual perception rehabilitation
      programme with interactive computer interface using motion tracking technology
      could be considered as a treatment option for stroke patients with visual
      perception impairment.

PMID- 19389747
TI  - Systems biology for identification of molecular networks in multiple sclerosis.

PMID- 19389748
TI  - Molecular network of the comprehensive multiple sclerosis brain-lesion proteome.
AB  - BACKGROUND: A recent proteomics study of multiple sclerosis (MS) lesion-specific
      proteome profiling clearly revealed a pivotal role of coagulation cascade
      proteins in chronic active demyelination. However, among thousands of proteins
      examined, nearly all of remaining proteins are yet to be characterized in terms
      of their implications in MS brain-lesion development. METHODS: By the systems
      biology approach using four different pathway analysis tools of bioinformatics,
      we studied molecular networks and pathways of the proteome dataset of acute
      plaques, chronic active plaques (CAP), and chronic plaques (CP). RESULTS: The
      database search on Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein
      analysis through evolutionary relationships (PANTHER) indicated the relevance of
      extracellular matrix (ECM)-mediated focal adhesion and integrin signaling to CAP
      and CP proteome. KeyMolnet disclosed a central role of the complex interaction
      among diverse cytokine signaling pathways in brain-lesion development at all
      disease stages, as well as a role of integrin signaling in CAP and CP. Ingenuity
      pathway analysis (IPA) identified the network constructed with a wide range of
      ECM components, such as collagen, type I alpha1, type I alpha2, type VI alpha2,
      type VI alpha3, fibronectin 1, fibulin 2, laminin alpha1, vitronectin, and
      heparan sulfate proteoglycan, as one of the networks highly relevant to CAP
      proteome. CONCLUSIONS: Although four distinct platforms produced diverse results,
      they commonly suggested a role of ECM and integrin signaling in development of
      chronic lesions of MS. These in silico observations indicate that the selective
      blockade of the interaction between ECM and integrins in brain lesions in situ
      would be a target for therapeutic intervention in MS.

PMID- 19389749
TI  - Proof of concept studies for tissue-protective agents in multiple sclerosis.
AB  - BACKGROUND: There is considerable interest in tissue-protective treatments for
      multiple sclerosis (MS). METHODS AND OBJECTIVES: We convened a group of MS
      clinical trialists and related researchers to discuss designs for proof of
      concept studies utilizing currently available data and assessment methods.
      RESULTS: Our favored design was a randomized, double-blind, parallel-group study
      of active treatment versus placebo focusing on changes in brain volume from a
      post-baseline scan (3-6 months after starting treatment) to the final visit 1
      year later. Study designs aimed at reducing residual deficits following acute
      exacerbations are less straightforward, depending greatly on the anticipated
      rapidity of treatment effect onset. CONCLUSIONS: The next step would be to
      perform one or more studies of potential tissue-protective agents with these
      designs in mind, creating the longitudinal data necessary to refine endpoint
      selection, eligibility criteria, and sample size estimates for future trials.

PMID- 19389750
TI  - The relationship between handedness and risk of multiple sclerosis.
AB  - BACKGROUND: Left-handedness has been studied as a marker for in-utero exposure to
      sex steroid hormones, and an increased risk of autoimmune and immune disorders
      among left-handed individuals has been suggested. OBJECTIVE: This study examines
      the relationship between hand preference and risk of multiple sclerosis, a
      presumed autoimmune disorder of unknown etiology. METHODS: The study population
      comprised participants in the Nurses' Health Study, an ongoing prospective cohort
      study of 121,701 female nurses in the United States with followup from 1976 to
      2002. The nurses were asked to report their natural hand preference (right, left,
      ambidextrous, forced to change). RESULTS: During followup 210 incident cases with
      multiple sclerosis were confirmed. A 62% increased risk of multiple sclerosis was
      observed among women who were naturally left handed as compared to those who were
      naturally right handed (95% CI: 1.04-2.53). CONCLUSIONS: This study suggests a
      modest increase in risk of multiple sclerosis among left-handed women. Further
      investigation of this relationship is suggested in other populations including
      both males and females. While the current results suggest that prenatal exposure
      to sex hormones may play a role in multiple sclerosis risk, direct examination of
      the relationship between in-utero hormone exposure and hand preference is
      necessary before any conclusions can be drawn.

PMID- 19389751
TI  - Association between MRI parameters and the MS severity scale: a 12 year follow-up
      study.
AB  - BACKGROUND: Several magnetic resonance imaging (MRI) parameters are known to be
      associated with short-term outcome in multiple sclerosis (MS) patients. MS
      related disability typically progresses over decades, stressing the need for
      longer follow-up studies. Until now, these studies are relatively sparse and,
      therefore, the predictive value of MRI parameters for clinical disability remains
      largely unknown. OBJECTIVE: To assess the predictive value of brain MRI
      parameters, which are obtained during the first 3.3 years of the study for
      overall disease severity as measured by the MS Severity Score (MSSS) after 12.2
      years follow-up. METHODS: Forty-six MS patients were included in the study. MRI
      parameters included both lesion loads and atrophy measures. Average and change
      parameters were calculated for MRI parameters and subsequently used as
      independent variables in regression models, while MSSS was the dependent
      variable. RESULTS: Follow-up (FU) was obtained in 43/46 patients (94%) and median
      expanded disability status scale (EDSS) score increased significantly from 2.5 to
      4.0. At last FU median MSSS was 4.3 (range 2.2-6.9). In univariate analyses, both
      change and cross-sectional T1-hypointense lesion load and ventricular atrophy
      measures were associated with MSSS. A multiple regression model included the
      change parameter of hypointense T1-lesion load (BHLL). This model explained 20%
      of variance in MSSS, which increased to 34% when type of disease (relapsing
      remitting or secondary progressive), age, and sex were entered additionally.
      CONCLUSION: MRI measures of axonal loss are associated with higher overall
      disease severity in MS patients.

PMID- 19389752
TI  - Allogeneic mesenchymal stem cells transplantation in treatment of multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous
      system. Umbilical cord derived mesenchymal stem cells are immunosuppressive. We
      transplanted mesenchymal stem cells in a patient with refractory progressive MS,
      and the disease course was stabilized after the transplantation. We postulate
      that mesenchymal stem cells have a potent immunosuppressive effect in vivo.

PMID- 19389753
TI  - Measuring up rates for adverse health behaviors in MS.

PMID- 19389756
TI  - Detection of 140 clinically relevant antibiotic-resistance genes in the plasmid
      metagenome of wastewater treatment plant bacteria showing reduced susceptibility
      to selected antibiotics.
AB  - To detect plasmid-borne antibiotic-resistance genes in wastewater treatment plant
      (WWTP) bacteria, 192 resistance-gene-specific PCR primer pairs were designed and
      synthesized. Subsequent PCR analyses on total plasmid DNA preparations obtained
      from bacteria of activated sludge or the WWTP's final effluents led to the
      identification of, respectively, 140 and 123 different resistance-gene-specific
      amplicons. The genes detected included aminoglycoside, beta-lactam,
      chloramphenicol, fluoroquinolone, macrolide, rifampicin, tetracycline,
      trimethoprim and sulfonamide resistance genes as well as multidrug efflux and
      small multidrug resistance genes. Some of these genes were only recently
      described from clinical isolates, demonstrating genetic exchange between clinical
      and WWTP bacteria. Sequencing of selected resistance-gene-specific amplicons
      confirmed their identity or revealed that the amplicon nucleotide sequence is
      very similar to a gene closely related to the reference gene used for primer
      design. These results demonstrate that WWTP bacteria are a reservoir for various
      resistance genes. Moreover, detection of about 64 % of the 192 reference
      resistance genes in bacteria obtained from the WWTP's final effluents indicates
      that these resistance determinants might be further disseminated in habitats
      downstream of the sewage plant.

PMID- 19389755
TI  - A family of fibrinogen-binding MSCRAMMs from Enterococcus faecalis.
AB  - We report that three (EF0089, EF2505 and EF1896, renamed here Fss1, Fss2 and
      Fss3, respectively, for Enterococcus faecalis surface protein) of the recently
      predicted MSCRAMMs (microbial surface components recognizing adhesive matrix
      molecules) in E. faecalis strain V583 bind fibrinogen (Fg). Despite an absence of
      extensive primary sequence homology, the three proteins appear to be related
      structurally. Within the N-terminal regions of the three enterococcal proteins,
      we identified pairs of putative IgG-like modules with a high degree of predicted
      structural similarity to the Fg-binding N2 and N3 domains of the staphylococcal
      MSCRAMMs ClfA and SdrG. A second N2N3-like segment was predicted in Fss1. Far-UV
      circular dichroism spectroscopy revealed that all four predicted N2N3-like
      regions are composed mainly of beta-sheets with only a minor proportion of alpha
      helices, which is characteristic of Ig-like folded domains. Three of the four
      identified enterococcal N2N3-like regions showed potent dose-dependent binding to
      Fg. However, the specificity of the Fg-binding MSCRAMMs differs, as indicated by
      far-Western blots, which showed that recombinant segments of the MSCRAMMs bound
      different Fg polypeptide chains. Enterococci grown in serum-supplemented broth
      adhere to Fg-coated surfaces, and inactivation in strain OG1RF of the gene
      encoding Fss2 resulted in reduced adherence, whilst complementation of the mutant
      restored full Fg adherence. Thus, E. faecalis contains a family of MSCRAMMs that
      structurally and functionally resemble the Fg-binding MSCRAMMs of staphylococci.

PMID- 19389757
TI  - Oxalate decarboxylase of the white-rot fungus Dichomitus squalens demonstrates a
      novel enzyme primary structure and non-induced expression on wood and in liquid
      cultures.
AB  - Oxalate decarboxylase (ODC) catalyses the conversion of oxalic acid to formic
      acid and CO(2) in bacteria and fungi. In wood-decaying fungi the enzyme has been
      linked to the regulation of intra- and extracellular quantities of oxalic acid,
      which is one of the key components in biological decomposition of wood. ODC
      enzymes are biotechnologically interesting for their potential in diagnostics,
      agriculture and environmental applications, e.g. removal of oxalic acid from
      industrial wastewaters. We identified a novel ODC in mycelial extracts of two
      wild-type isolates of Dichomitus squalens, and cloned the corresponding Ds-odc
      gene. The primary structure of the Ds-ODC protein contains two conserved Mn
      binding cupin motifs, but at the N-terminus, a unique, approximately 60 aa
      alanine-serine-rich region is found. Real-time quantitative RT-PCR analysis
      confirmed gene expression when the fungus was cultivated on wood and in liquid
      medium. However, addition of oxalic acid in liquid cultures caused no increase in
      transcript amounts, thereby indicating a constitutive rather than inducible
      expression of Ds-odc. The detected stimulation of ODC activity by oxalic acid is
      more likely due to enzyme activation than to transcriptional upregulation of the
      Ds-odc gene. Our results support involvement of ODC in primary rather than
      secondary metabolism in fungi.

PMID- 19389758
TI  - Carbohydrate-binding properties of a separately folding protein module from beta
      1,3-glucanase Lic16A of Clostridium thermocellum.
AB  - The multi-modular non-cellulosomal endo-1,3(4)-beta-glucanase Lic16A from
      Clostridium thermocellum contains a so-called X module (denoted as CBMX) near the
      N terminus of the catalytic module (191-426 aa). Melting of X-module-containing
      recombinant proteins revealed an independent folding of the module. CBMX was
      isolated and studied as a separate fragment. It was shown to bind to various
      insoluble polysaccharides, including xylan, pustulan, chitin, chitosan, yeast
      cell wall glucan, Avicel and bacterial crystalline cellulose. CBMX thus contains
      a hitherto unknown carbohydrate-binding module (CBM54). It did not bind soluble
      polysaccharides on which Lic16A is highly active. Ca2+ ions had effects on the
      binding, e.g. stimulated complex formation with chitosan, which was observed only
      in the presence of Ca2+. The highest affinity to CBMX was shown for xylan
      (binding constant K=3.1x10(4) M(-1)), yeast cell wall glucan (K=1.4x10(5) M(-1))
      and chitin (K=3.3.10(5) M(-1) in the presence of Ca2+). Lic16A deletion
      derivatives lacking CBMX had lower affinity to lichenan and laminarin and a
      slight decrease in optimum temperature and thermostability. However, the specific
      activity was not significantly affected.

PMID- 19389759
TI  - Ferrous iron-binding protein Omb of Salmonella enterica serovar Choleraesuis
      promotes resistance to hydrophobic antibiotics and contributes to its virulence.
AB  - Salmonella enterica serovar Choleraesuis (SC) is an important enteric pathogen
      that causes serious systemic infections in swine and humans. To identify the
      genes required for resistance to antimicrobial peptides, we constructed a bank of
      SC transposon mutants and screened them for hypersensitivity to the cationic
      peptide polymyxin B. Here we report one isolated polymyxin B-susceptible mutant
      that also exhibited increased sensitivity toward human neutrophil peptide alpha
      defensin 1 (HNP-1) and hydrophobic antibiotics including erythromycin and
      novobiocin. The mutant had a mutation in an ORF identified as outer membrane beta
      barrel protein gene omb. The purified recombinant Omb protein was characterized
      as a ferrous iron-binding protein. The constructed omb isogenic mutant grew more
      slowly in iron-limiting conditions than the wild-type (WT) parent strain. In
      addition, compared with the WT strain, the omb mutant exhibited an increase in
      net negative charge upon the cell surface and was more easily killed by polymyxin
      B, HNP-1 and hydrophobic antibiotics. The omb gene was transcribed, regardless of
      the iron content within the growth medium, and the Omb protein appeared
      exclusively in the outer membrane fraction. Infection experiments demonstrated
      virulence attenuation when the mutant was administered orally or
      intraperitoneally to mice. This study indicates that Omb is a previously
      unrecognized ferrous iron-binding protein. In vivo, Omb may be involved in the
      acquisition of ferrous iron during the initial stages of SC infection and appears
      to be an important virulence factor for SC in mice.

PMID- 19389760
TI  - Function of the N-terminal region of the phosphate-sensing histidine kinase,
      SphS, in Synechocystis sp. PCC 6803.
AB  - In Synechocystis sp. PCC 6803 the histidine kinase SphS (sll0337) is involved in
      transcriptional activation of the phosphate (Pi)-acquisition system which
      includes alkaline phosphatase (AP). The N-terminal region of SphS contains both a
      hydrophobic region and a Per-Arnt-Sim (PAS) domain. The C-terminal region has a
      highly conserved transmitter domain. Immunological localization studies on
      heterologously expressed SphS in Escherichia coli indicate that the hydrophobic
      region is important for membrane localization. In order to evaluate the function
      of the N-terminal region of SphS, deletion mutants under the control of the
      native promoter were analysed for in vivo AP activity. Deletion of the N-terminal
      hydrophobic region resulted in loss of AP activity under both Pi-deficient and Pi
      sufficient conditions. Substitution of the hydrophobic region of SphS with that
      from the Ni2+-sensing histidine kinase, NrsS, resulted in the same induction
      characteristics as SphS. Deletion of the PAS domain resulted in the constitutive
      induction of AP activity regardless of Pi availability. To characterize the PAS
      domain in more in detail, four amino acid residues conserved in the PAS domain
      were substituted with Ala. Among the mutants R121A constitutively expressed AP
      activity, suggesting that R121 is important for the function of the PAS domain.
      Our observations indicated that the presence of a transmembrane helix in the N
      terminal region of SphS is critical for activity and that the PAS domain is
      involved in perception of Pi availability.

PMID- 19389761
TI  - Contribution of RecFOR machinery of homologous recombination to cell survival
      after loss of a restriction-modification gene complex.
AB  - Loss of a type II restriction-modification (RM) gene complex, such as EcoRI, from
      a bacterial cell leads to death of its descendent cells through attack by
      residual restriction enzymes on undermethylated target sites of newly synthesized
      chromosomes. Through such post-segregational host killing, these gene complexes
      impose their maintenance on their host cells. This finding led to the rediscovery
      of type II RM systems as selfish mobile elements. The host prokaryote cells were
      found to cope with such attacks through a variety of means. The RecBCD pathway of
      homologous recombination in Escherichia coli repairs the lethal lesions on the
      chromosome, whilst it destroys restricted non-self DNA. recBCD homologues,
      however, appear very limited in distribution among bacterial genomes, whereas
      homologues of the RecFOR proteins, responsible for another pathway, are
      widespread in eubacteria, just like the RM systems. In the present work,
      therefore, we examined the possible contribution of the RecFOR pathway to cell
      survival after loss of an RM gene complex. A recF mutation reduced survival in an
      otherwise rec-positive background and, more severely, in a recBC sbcBC
      background. We also found that its effect is prominent in the presence of
      specific non-null mutant forms of the RecBCD enzyme: the resistance to killing
      seen with recC1002, recC1004, recC2145 and recB2154 is severely reduced to the
      level of a null recBC allele when combined with a recF, recO or recR mutant
      allele. Such resistance was also dependent on RecJ and RecQ functions. UV
      resistance of these non-null recBCD mutants is also reduced by recF, recJ or recQ
      mutation. These results demonstrate that the RecFOR pathway of recombination can
      contribute greatly to resistance to RM-mediated host killing, depending on the
      genetic background.

PMID- 19389762
TI  - Comparative proteomic analysis of an Aspergillus fumigatus mutant deficient in
      glucosidase I (AfCwh41).
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 quality
      control systems in mammalian cells. Previously, we identified the gene encoding
      alpha-glucosidase I in the opportunistic human fungal pathogen Aspergillus
      fumigatus, namely Afcwh41. Deletion of the Afcwh41 gene results in a severe
      reduction of conidia formation, a temperature-sensitive deficiency of cell wall
      integrity, and abnormalities of polar growth and septation. An upregulation of
      the genes encoding Rho-type GTPases was also observed, which suggests activation
      of the cell wall integrity pathway in the mutant. Using 2D gel analysis, we
      revealed that the proteins involved in protein assembly, ubiquitin-mediated
      degradation and actin organization are altered in the DeltaAfcwh41 mutant.
      Evidence was obtained for a defect in the polarized localization of the actin
      cytoskeleton in the mutant. Our results suggest that blocking of the glucose
      trimming in A. fumigatus might induce accumulation of misfolded proteins in the
      endoplasmic reticulum; these misfolded proteins are probably required for cell
      wall synthesis and thus activate the cell wall integrity pathway, which then
      causes the abnormal polarity associated with the DeltaAfcwh41 mutant.

PMID- 19389763
TI  - SwrAA activates poly-gamma-glutamate synthesis in addition to swarming in
      Bacillus subtilis.
AB  - Poly-gamma-glutamic acid (gamma-PGA) is an extracellular polymer produced by
      various strains of Bacillus. Iotat was first described as the component of the
      capsule in Bacillus anthracis, where it plays a relevant role in virulence. gamma
      PGA is also a distinctive component of 'natto', a traditional Japanese food
      consisting of soybean fermented by Bacillus subtilis (natto). Domesticated B.
      subtilis strains do not synthesize gamma-PGA although they possess the functional
      biosynthetic pgs operon. In the present work we explore the correlation between
      the genetic determinants, swrAA and degU, which allow a derivative of the
      domestic strain JH642 to display a mucoid colony morphology on LB agar plates due
      to the production of gamma-PGA. Full activation of the pgs operon requires the co
      presence of SwrAA and the phosphorylated form of DegU (DegU approximately P). The
      presence of either DegU approximately P or SwrAA alone has only marginal effects
      on pgs operon transcription and gamma-PGA production. Although SwrAA was
      identified as necessary for swarming and full swimming motility together with
      DegU, we show that motility is not involved in gamma-PGA production. Activation
      of gamma-PGA synthesis is therefore a motility-independent phenotype in which
      SwrAA and DegU approximately P display a cooperative effect.

PMID- 19389764
TI  - An iron-regulated LysR-type element mediates antimicrobial peptide resistance and
      virulence in Yersinia pseudotuberculosis.
AB  - During the course of its infection of the mammalian digestive tract, the entero
      invasive, Gram-negative bacterium Yersinia pseudotuberculosis must overcome
      various hostile living conditions (notably, iron starvation and the presence of
      antimicrobial compounds produced in situ). We have previously reported that in
      vitro bacterial growth during iron deprivation raises resistance to the
      antimicrobial peptide polymyxin B; here, we show that this phenotype is mediated
      by a chromosomal gene (YPTB0333) encoding a transcriptional regulator from the
      LysR family. We determined that the product of YPTB0333 is a pleiotropic
      regulator which controls (in addition to its own expression) genes encoding the
      Yfe iron-uptake system and polymyxin B resistance. Lastly, by using a mouse model
      of oral infection, we demonstrated that YPTB0333 is required for colonization of
      Peyer's patches and mesenteric lymph nodes by Y. pseudotuberculosis.

PMID- 19389765
TI  - The OxyR homologue in Tannerella forsythia regulates expression of oxidative
      stress responses and biofilm formation.
AB  - Tannerella forsythia is an anaerobic periodontal pathogen that encounters
      constant oxidative stress in the human oral cavity due to exposure to air and
      reactive oxidative species from coexisting dental plaque bacteria as well as
      leukocytes. In this study, we sought to characterize a T. forsythia ORF with
      close similarity to bacterial oxidative stress response sensor protein OxyR. To
      analyse the role of this OxyR homologue, a gene deletion mutant was constructed
      and characterized. Aerotolerance, survival after hydrogen peroxide challenge and
      transcription levels of known bacterial antioxidant genes were then determined.
      Since an association between oxidative stress and biofilm formation has been
      observed in bacterial systems, we also investigated the role of the OxyR protein
      in biofilm development by T. forsythia. Our results showed that aerotolerance,
      sensitivity to peroxide challenge and the expression of oxidative stress response
      genes were significantly reduced in the mutant as compared with the wild-type
      strain. Moreover, the results of biofilm analyses showed that, as compared with
      the wild-type strain, the oxyR mutant showed significantly less autoaggregation
      and a reduced ability to form mixed biofilms with Fusobacterium nucleatum. In
      conclusion, a gene annotated in the T. forsythia genome as an oxyR homologue was
      characterized. Our studies showed that the oxyR homologue in T. forsythia
      constitutively activates antioxidant genes involved in resistance to peroxides as
      well as oxygen stress (aerotolerance). In addition, the oxyR deletion attenuates
      biofilm formation in T. forsythia.

PMID- 19389766
TI  - Fratricide in Streptococcus pneumoniae: contributions and role of the cell wall
      hydrolases CbpD, LytA and LytC.
AB  - Pneumococci that have developed the competent state kill and lyse non-competent
      sister cells and members of closely related species during co-cultivation in
      vitro. The key component in this process, called fratricide, is the product of
      the late competence gene cbpD. In addition, the peptidoglycan hydrolases LytA and
      LytC are required for efficient lysis of target cells. Here, we have investigated
      the relative contribution and possible role of each of the proteins mentioned
      above. Previous studies have shown that CbpD is produced exclusively by competent
      cells, whereas LytA and LytC can be provided by the competent attackers as well
      as the non-competent target cells. By using an improved assay to compare the
      effect of cis- versus trans-acting LytA and LytC, we were able to show that
      target cells are lysed much more efficiently when LytA and LytC are provided in
      cis, i.e. by the target cells themselves. Western analysis demonstrated that
      considerable amounts of LytC are present in the growth medium. In contrast, we
      were not able to detect any extracellular LytA. This finding indicates that LytA-
      and LytC-mediated fratricide represent different processes. In the absence of
      LytA and LytC, only a tiny fraction of the target cells were lysed, demonstrating
      that CbpD does not function efficiently on its own. However, in the presence of 1
      mM EDTA, the fraction of target cells lysed directly by CbpD increased
      dramatically, indicating that divalent cations are involved in the regulation of
      fratricide under natural conditions.

PMID- 19389767
TI  - The extracellular metalloprotease of Vibrio tubiashii directly inhibits its
      extracellular haemolysin.
AB  - Vibrio tubiashii is a re-emerging pathogen of molluscs that secretes a variety of
      extracellular products (ECPs), including a metalloprotease and a
      cytolysin/haemolysin. Previously, we reported that the V. tubiashii haemolysin
      locus consists of two ORFs (vthB and vthA), similar to that of the homologous
      haemolysin genes (vvhB and vvhA) found in Vibrio vulnificus. Here, we demonstrate
      that the concomitant expression of both V. tubiashii genes resulted in
      significantly higher haemolytic activity than the vthA gene alone. In addition,
      we created a VthAB- mutant strain of V. tubiashii that was virtually devoid of
      haemolytic activity in liquid media. Interestingly, significant production of an
      additional haemolysin(s) was observed on blood plates. Moreover, we have
      previously reported that in V. tubiashii, proteolytic and haemolytic activities
      are inversely produced during bacterial growth. Here, we study this correlation
      in more detail and present evidence that the VtpA metalloprotease inhibits
      haemolytic activity in culture supernatants, based on the following evidence: (i)
      loss of metalloprotease activity by either mutation or EDTA inhibition resulted
      in increased haemolytic activity; (ii) overexpression of the vtpA gene resulted
      in decreased haemolytic activity; (iii) purified VtpA metalloprotease directly
      diminished haemolytic activity by purified VthA haemolysin. Importantly, we found
      not only that vthAB gene expression remained high throughout growth but also that
      there were no dramatic differences in vthAB gene expression between the parent
      and VtpA- mutant strains. Thus, our results strongly suggest that the V.
      tubiashii metalloprotease directly targets its haemolysin.

PMID- 19389768
TI  - A two-component system is required for colonization of host cells by
      meningococcus.
AB  - In order to adapt to changing environments, bacteria have evolved two-component
      systems (TCSs) that are able to sense and respond to environmental stimuli. The
      signal perception relies on a sensor protein whose activation allows rapid
      adaptation through transcriptional regulation achieved by the regulatory protein.
      The ability to adhere to and grow on the surface of human host cells is an
      absolute requirement for many pathogens, including Neisseria meningitidis, in
      order to colonize new hosts and to disseminate inside their host. Among the four
      TCSs encoded in the meningococcus genome, only the PhoQ (MisS)/PhoP (MisR) system
      has been shown to constitute a functional signal transduction circuit. To
      investigate the involvement of this TCS in the adaptation process requisite for
      host cell colonization, we have tested the ability to grow on host cells of a
      mutant inactivated for the sensor of the TCS. Our results demonstrate the
      involvement of the TCS in the adaptation of the meningococcus to growth on host
      cells. We show that the expression of the PhoQ (MisS)/PhoP (MisR) TCS is cell
      contact controlled. Furthermore, this TCS controls the regulation of a group of
      genes, the REP2 regulon, previously shown to be cell-contact regulated and to
      encode functions crucial for the adaptation of the bacterium to host cell
      colonization. Thus, we provide evidence that one of the four TCSs existing in N.
      meningitidis contributes to the adaptation of the pathogen to growth on host
      cells.

PMID- 19389769
TI  - Sequence variations in RepMP2/3 and RepMP4 elements reveal intragenomic
      homologous DNA recombination events in Mycoplasma pneumoniae.
AB  - The gene encoding major adhesin protein P1 of Mycoplasma pneumoniae, MPN141,
      contains two DNA sequence stretches, designated RepMP2/3 and RepMP4, which
      display variation among strains. This variation allows strains to be
      differentiated into two major P1 genotypes (1 and 2) and several variants.
      Interestingly, multiple versions of the RepMP2/3 and RepMP4 elements exist at
      other sites within the bacterial genome. Because these versions are closely
      related in sequence, but not identical, it has been hypothesized that they have
      the capacity to recombine with their counterparts within MPN141, and thereby
      serve as a source of sequence variation of the P1 protein. In order to determine
      the variation within the RepMP2/3 and RepMP4 elements, both within the bacterial
      genome and among strains, we analysed the DNA sequences of all RepMP2/3 and
      RepMP4 elements within the genomes of 23 M. pneumoniae strains. Our data
      demonstrate that: (i) recombination is likely to have occurred between two
      RepMP2/3 elements in four of the strains, and (ii) all previously described P1
      genotypes can be explained by inter-RepMP recombination events. Moreover, the
      difference between the two major P1 genotypes was reflected in all RepMP
      elements, such that subtype 1 and 2 strains can be differentiated on the basis of
      sequence variation in each RepMP element. This implies that subtype 1 and subtype
      2 strains represent evolutionarily diverged strain lineages. Finally, a
      classification scheme is proposed in which the P1 genotype of M. pneumoniae
      isolates can be described in a sequence-based, universal fashion.

PMID- 19389770
TI  - Evaluation of signal peptide prediction algorithms for identification of
      mycobacterial signal peptides using sequence data from proteomic methods.
AB  - Secreted proteins play an important part in the pathogenicity of Mycobacterium
      tuberculosis, and are the primary source of vaccine and diagnostic candidates. A
      majority of these proteins are exported via the signal peptidase I-dependent
      pathway, and have a signal peptide that is cleaved off during the secretion
      process. Sequence similarities within signal peptides have spurred the
      development of several algorithms for predicting their presence as well as the
      respective cleavage sites. For proteins exported via this pathway, algorithms
      exist for eukaryotes, and for Gram-negative and Gram-positive bacteria. However,
      the unique structure of the mycobacterial membrane raises the question of whether
      the existing algorithms are suitable for predicting signal peptides within
      mycobacterial proteins. In this work, we have evaluated the performance of nine
      signal peptide prediction algorithms on a positive validation set, consisting of
      57 proteins with a verified signal peptide and cleavage site, and a negative set,
      consisting of 61 proteins that have an N-terminal sequence that confirms the
      annotated translational start site. We found the hidden Markov model of SignalP
      v3.0 to be the best-performing algorithm for predicting the presence of a signal
      peptide in mycobacterial proteins. It predicted no false positives or false
      negatives, and predicted a correct cleavage site for 45 of the 57 proteins in the
      positive set. Based on these results, we used the hidden Markov model of SignalP
      v3.0 to analyse the 10 available annotated proteomes of mycobacterial species,
      including annotations of M. tuberculosis H37Rv from the Wellcome Trust Sanger
      Institute and the J. Craig Venter Institute (JCVI). When excluding proteins with
      transmembrane regions among the proteins predicted to harbour a signal peptide,
      we found between 7.8 and 10.5% of the proteins in the proteomes to be putative
      secreted proteins. Interestingly, we observed a consistent difference in the
      percentage of predicted proteins between the Sanger Institute and JCVI. We have
      determined the most valuable algorithm for predicting signal peptidase I
      processed proteins of M. tuberculosis, and used this algorithm to estimate the
      number of mycobacterial proteins with the potential to be exported via this
      pathway.

PMID- 19389771
TI  - DNA microarray analysis of global gene regulation by A-factor in Streptomyces
      griseus.
AB  - A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) is a microbial
      hormone that triggers morphological differentiation and secondary metabolism in
      Streptomyces griseus. The effects of A-factor on global gene expression were
      determined by DNA microarray analysis of transcriptomes obtained with the A
      factor-deficient mutant DeltaafsA. A-factor was added at a concentration of 25 ng
      ml(-1) to mutant DeltaafsA at the middle of the exponential growth phase, and RNA
      samples were prepared from the cells grown after A-factor addition for a further
      5, 15 and 30 min, and 1, 2, 4, 8 and 12 h. The effects of A-factor on
      transcription of all protein-coding genes of S. griseus were evaluated by
      comparison of the transcriptomes with those obtained from cells grown in the
      absence of A-factor. Analysis of variance among the transcriptomes revealed that
      477 genes, which were dispersed throughout the chromosome, were differentially
      expressed during the 12 h after addition of A-factor, when evaluated by specific
      criteria. Quality threshold clustering analysis with regard to putative
      polycistronic transcriptional units and levels of upregulation predicted that 152
      genes belonging to 74 transcriptional units were probable A-factor-inducible
      genes. Competitive electrophoretic mobility shift assays using DNA fragments
      including putative promoter regions of these 74 transcriptional units suggested
      that AdpA bound 37 regions to activate 72 genes in total. Many of these A-factor
      inducible genes encoded proteins of unknown function, suggesting that the A
      factor regulatory cascade of S. griseus affects gene expression at a specific
      time point more profoundly than expected.

PMID- 19389772
TI  - Characterization of a novel protective monoclonal antibody that recognizes an
      epitope common to Vibrio cholerae Ogawa and Inaba serotypes.
AB  - A novel protective monoclonal antibody (mAb) that recognizes a lipopolysaccharide
      (LPS) epitope common between serotypes Ogawa and Inaba of the O1 serogroup of
      Vibrio cholerae was characterized and the potential to develop peptide mimics of
      this protective LPS epitope was investigated. mAb 72.1 recognizes both Ogawa and
      Inaba LPS and it is vibriocidal and protective in passive immunization against
      infection by strains of both serotypes. The cDNA-derived amino acid sequence of
      mAb 72.1 is closely related to the previously characterized mAb ZAC-3, which is
      thought to recognize an epitope in the lipid A core region of O1 LPS. In an
      attempt to develop a peptide mimic-based vaccine against V. cholerae, phage
      display libraries were screened with mAb 72.1 and 11 peptide mimics were
      identified. Remarkably, all of the peptide sequences identified from linear phage
      display libraries contained two cysteine residues, suggesting that mAb 72.1
      preferentially binds to peptides constrained with a disulphide bond. One of the
      peptide mimics was immunologically characterized. Although immunization of mice
      with this peptide mimic conjugated to KLH elicited antibodies against the peptide
      itself, these antibodies did not cross-react with Ogawa or Inaba LPS.
      Effectiveness of a peptide mimic as a vaccine may depend on how well the peptide
      can mimic the carbohydrate interactions when binding to the anti-carbohydrate
      antibody. Thus, investigating how peptides and LPS bind to mAb 72.1 may be useful
      in improving current peptide mimics or designing more effective peptide mimics.
      Identification and characterization of novel protective anti-LPS antibodies may
      be useful in studying protective epitopes of LPS, which may help develop LPS
      based therapeutics against V. cholerae.

PMID- 19389773
TI  - Surface-associated lipoprotein PpmA of Streptococcus pneumoniae is involved in
      colonization in a strain-specific manner.
AB  - Streptococcus pneumoniae produces two surface-associated lipoproteins that share
      homology with two distinct families of peptidyl-prolyl isomerases (PPIases), the
      streptococcal lipoprotein rotamase A (SlrA) and the putative proteinase
      maturation protein A (PpmA). Previously, we have demonstrated that SlrA has
      PPIase activity, and that the enzyme plays a role in pneumococcal virulence.
      Here, we investigated the contribution of PpmA to pneumococcal pathogenesis.
      Pneumococcal mutants of D39 and TIGR4 lacking the gene encoding PpmA were less
      capable of persisting in the nasopharynx of mice, demonstrating the contribution
      of PpmA to pneumococcal colonization. This observation was partially confirmed in
      vitro, as the pneumococcal mutants NCTC10319DeltappmA and TIGR4DeltacpsDeltappmA,
      but not D39DeltacpsDeltappmA, were impaired in adherence to Detroit 562
      pharyngeal cells. This suggests that the contribution of PpmA to pneumococcal
      colonization is not solely the result of its role in adherence to epithelial
      cells. Deficiency in PpmA did not result in reduced binding to various
      extracellular matrix and serum proteins. Similar to SlrA, we observed that PpmA
      was involved in immune evasion. Uptake of PpmA-deficient D39Deltacps and
      NCTC10319 by human polymorphonuclear leukocytes was significantly enhanced
      compared to the isogenic wild-types. In addition, ingestion of D39DeltappmA, but
      not that of either NCTC10319DeltappmA or TIGR4DeltappmA, by murine macrophage
      cell line J774 was also enhanced, whereas intracellular killing remained
      unaffected. We conclude that PpmA contributes to the early stages of infection,
      i.e. colonization. The contribution of PpmA to virulence can be explained by its
      strain-specific role in adherence to epithelial cells and contribution to the
      evasion of phagocytosis.

PMID- 19389775
TI  - Transmembrane topology of the AbsA1 sensor kinase of Streptomyces coelicolor.
AB  - The sensor kinase AbsA1 (SCO3225) phosphorylates the response regulator AbsA2
      (SCO3226) and dephosphorylates AbsA2 approximately P. The phosphorylated response
      regulator represses antibiotic biosynthesis operons in Streptomyces coelicolor.
      AbsA1 was predicted to have an atypical transmembrane topology, and the location
      of its signal-sensing domain is not readily obvious. To better understand this
      protein and to gain insight into its signal response mechanism, we determined its
      transmembrane topology using fusions of absA1 to egfp, which is believed to be
      the first application of this approach to transmembrane topology in the
      actinomycetes. Our results are in agreement with the in silico topological
      predictions and demonstrate that AbsA1 has five transmembrane domains, four near
      the N terminus and one near the C terminus. Unlike most sensor kinases, the
      largest extracellular portion of AbsA1 is at the C terminus.

PMID- 19389774
TI  - Extensive genomic diversity of closely related Wolbachia strains.
AB  - Using microarray-based comparative genome hybridization (mCGH), the genomic
      content of Wolbachia pipientis wMel from Drosophila melanogaster was compared to
      the closely related Wolbachia from D. innubila (wInn), D. santomea (wSan), and
      three strains from D. simulans (wAu, wRi, wSim). A large number of auxiliary
      genes are identified in these five strains, with most absent/divergent genes
      being unique to a given strain. Each strain caused an average of approximately 60
      genes to be removed from the core genome. As such, these organisms do not appear
      to have the streamlined genomes expected of obligate intracellular bacteria.
      Prophage, hypothetical and ankyrin repeat genes are over-represented in the
      absent/divergent genes, with 21-87% of absent/divergent genes coming from
      prophage regions. The only wMel region absent/divergent in all five query strains
      is that containing WD_0509 to WD_0511, including a DNA mismatch repair protein
      MutL-2, a degenerate RNase, and a conserved hypothetical protein. A region
      flanked by the two portions of the WO-B prophage in wMel is found in four of the
      five Wolbachia strains as well as on a plasmid of a rickettsial endosymbiont of
      Ixodes scapularis, suggesting lateral gene transfer between these two obligate
      intracellular species. Overall, these insect-associated Wolbachia have highly
      mosaic genomes, with lateral gene transfer playing an important role in their
      diversity and evolution.

PMID- 19389776
TI  - Proteomic analysis of the adaptive response of Salmonella enterica serovar
      Typhimurium to growth under anaerobic conditions.
AB  - In order to survive in the host and initiate infection, Salmonella enterica needs
      to undergo a transition between aerobic and anaerobic growth by modulating its
      central metabolic pathways. In this study, a comparative analysis of the proteome
      of S. enterica serovar Typhimurium grown in the presence or absence of oxygen was
      performed. The most prominent changes in expression were measured in a
      semiquantitative manner using difference in-gel electrophoresis (DIGE) to reveal
      the main protein factors involved in the adaptive response to anaerobiosis. A
      total of 38 proteins were found to be induced anaerobically, while 42 were
      repressed. The proteins of interest were in-gel digested with trypsin and
      identified by MALDI TOF mass spectrometry using peptide mass fingerprinting. In
      the absence of oxygen, many fermentative enzymes catalysing reactions in the
      mixed-acid or arginine fermentations were overexpressed. In addition, the enzyme
      fumarate reductase, which is known to provide an alternative electron acceptor
      for the respiratory chains in the absence of oxygen, was shown to be induced.
      Increases in expression of several glycolytic and pentose phosphate pathway
      enzymes, as well as two malic enzymes, were detected, suggesting important roles
      for these in anaerobic metabolism. Substantial decreases in expression were
      observed for a large number of periplasmic transport proteins. The majority of
      these are involved in the uptake of amino acids and peptides, but permeases
      transporting iron, thiosulphate, glucose/galactose, glycerol 3-phosphate and
      dicarboxylic acids were also repressed. Decreases in expression were also
      observed for a superoxide dismutase, ATP synthase, inositol monophosphatase, and
      several chaperone and hypothetical proteins. The changes were monitored in two
      different isolates, and despite their very similar expression patterns, some
      variability in the adaptive response to anaerobiosis was also observed.

PMID- 19389777
TI  - The cell wall galactomannan antigen from Malassezia furfur and Malassezia
      pachydermatis contains beta-1,6-linked linear galactofuranosyl residues and its
      detection has diagnostic potential.
AB  - Lipophilic yeasts of the genus Malassezia are associated with several skin
      diseases, such as pityriasis versicolor, Malassezia folliculitis, seborrhoeic
      dermatitis and atopic dermatitis, and are also increasingly associated with
      catheter-related fungaemia. The cell wall components of pathogenic micro
      organisms behave as an antigen and/or ligand of the innate immune response. Live
      cells of Malassezia furfur and Malassezia pachydermatis did not react with an
      anti-alpha-1,2-mannoside antibody. However, they showed a strong hydrophobicity
      and reactivity with an anti-beta-1,3-glucan antibody compared to those of C.
      albicans. The cell wall polysaccharides of M. furfur and M. pachydermatis were
      isolated and their structures analysed by (1)H and (13)C NMR experiments. Both
      polysaccharides were shown to be beta-1,6-linked linear galactofuranosyl polymers
      with a small amount of mannan. The presence of galactomannan on cells of
      Malassezia species has not been described previously. The galactomannan did not
      react with an anti-Aspergillus fumigatus monoclonal antibody which has
      specificity for beta-1,5-linked galactofuranosyl residues. An anti-M. furfur
      antibody strongly reacted with the galactomannans of M. furfur and M.
      pachydermatis, but did not react with the galactomannans of Trichophyton rubrum,
      A. fumigatus or Fonsecaea pedrosoi. The characteristics of the anti-M. furfur
      antibody suggest that there is potential for diagnosis of Malassezia infections
      by antigen detection.

PMID- 19389778
TI  - The MrpA, MrpB and MrpD subunits of the Mrp antiporter complex in Bacillus
      subtilis contain membrane-embedded and essential acidic residues.
AB  - Bacillus subtilis Mrp is a unique Na+/H+ antiporter with a multicomponent
      structure consisting of the mrpABCDEFG gene products. We have previously reported
      that the conserved and putative membrane-embedded Glu-113, Glu-657, Asp-743 and
      Glu-747 of MrpA (ShaA) are essential for the transport function. In this study,
      we further investigated the functional involvement of the equivalent conserved
      acidic residues of other Mrp proteins in heterologous Escherichia coli and
      natural B. subtilis backgrounds. Asp-121 of MrpB and Glu-137 of MrpD were
      additionally identified to be essential for the transport function in both
      systems. Glu-137 of MrpD and Glu-113 of MrpA were found to be conserved in the
      homologous MrpD/MrpA proteins as well as in the homologous subunits of H+
      translocating primary active transporters such as Nuo and Mbh, suggesting their
      critical role in ion binding. The remaining essential acidic residues clustered
      in the C-terminal domain of MrpA (Glu-657, Asp-743 and Glu-747) and MrpB (Asp
      121); these subunits are fused in some Gram-negative species. It is possible that
      the MrpA, MrpB and MrpD subunits, which contain essential transmembrane acidic
      residues, form the ion translocation site(s) of the Mrp antiporter complex.

PMID- 19389779
TI  - Inactivation of the Lactococcus lactis high-affinity phosphate transporter
      confers oxygen and thiol resistance and alters metal homeostasis.
AB  - Numerous strategies allowing bacteria to detect and respond to oxidative
      conditions depend on the cell redox state. Here we examined the ability of
      Lactococcus lactis to survive aerobically in the presence of the reducing agent
      dithiothreitol (DTT), which would be expected to modify the cell redox state and
      disable the oxidative stress response. DTT inhibited L. lactis growth at 37
      degrees C in aerobic conditions, but not in anaerobiosis. Mutants selected as DTT
      resistant all mapped to the pstFEDCBA locus, encoding a high-affinity phosphate
      transporter. Transcription of pstFEDCBA and a downstream putative regulator of
      stress response, phoU, was deregulated in a pstA strain, but amounts of major
      oxidative stress proteins were unchanged. As metals participate in oxygen radical
      formation, we compared metal sensitivity of wild-type and pstA strains. The pstA
      mutant showed approximately 100-fold increased resistance to copper and zinc.
      Furthermore, copper or zinc addition exacerbated the sensitivity of a wild-type
      L. lactis strain to DTT. Inactivation of pstA conferred a more general resistance
      to oxidative stress, alleviating the oxygen- and thermo-sensitivity of a clpP
      mutant. This study establishes a role for the pst locus in metal homeostasis,
      suggesting that pst inactivation lowers intracellular reactivity of copper and
      zinc, which would limit bacterial sensitivity to oxygen.

PMID- 19389780
TI  - Pseudomonas aeruginosa extracellular products inhibit staphylococcal growth, and
      disrupt established biofilms produced by Staphylococcus epidermidis.
AB  - Multiple bacterial species often coexist as communities, and compete for
      environmental resources. Here, we describe how an opportunistic pathogen,
      Pseudomonas aeruginosa, uses extracellular products to interact with the
      nosocomial pathogen Staphylococcus epidermidis. S. epidermidis biofilms and
      planktonic cultures were challenged with P. aeruginosa supernatant cultures
      overnight. Results indicated that quorum-sensing-controlled factors from P.
      aeruginosa supernatant inhibited S. epidermidis growth in planktonic cultures. We
      also found that P. aeruginosa extracellular products, mainly polysaccharides,
      disrupted established S. epidermidis biofilms. Cellulase-treated P. aeruginosa
      supernatant, and supernatant from pelA, pslF and pelApslBCD mutants, which are
      deficient in polysaccharide biosynthesis, diminished the disruption of S.
      epidermidis biofilms. In contrast, S. epidermidis supernatant in overnight
      cultures had no effect on established P. aeruginosa biofilms and planktonic
      growth. These findings reveal that P. aeruginosa extracellular products are
      important microbial competition factors that overcome competition with S.
      epidermidis, and the results may provide clues for the development of a novel
      strategy for controlling S. epidermidis biofilms.

PMID- 19389781
TI  - Mce3R, a TetR-type transcriptional repressor, controls the expression of a
      regulon involved in lipid metabolism in Mycobacterium tuberculosis.
AB  - The mce operons constitute four homologous regions in the Mycobacterium
      tuberculosis genome, each of which has 8-13 ORFs. Although the function of the
      Mce protein family has not been clearly established, its members are believed to
      be membrane lipid transporters. Based on functional experiments, we found that
      the regulator of the mce3 locus, Mce3R, negatively regulates the expression of
      the Rv1933c-Rv1935c and Rv1936-Rv1941 transcriptional units. These operons are
      adjacent to one another and divergently transcribed. The predicted functions of
      most of these genes are related to either lipid metabolism or redox reactions.
      Bioinformatic analysis of the 5' UTR sequences of the differentially expressed
      genes allowed us to define a putative Mce3R motif. Importantly, the Mce3R motif
      was present six and three times in the mce3R-yrbE3A and Rv1935c-Rv1936 intergenic
      regions, respectively. Two occurrences of this motif mapped within the two
      regions of the mce3 operon that were protected by Mce3R in a footprinting
      analysis, thus indicating that this motif is likely to serve as an operator site
      for the Mce3R regulator in the promoter. In addition, alterations in the lipid
      content of M. tuberculosis were detected in the absence of Mce3R. Taken together,
      these results suggest that Mce3R controls the expression of both the putative
      transport system encoded in the mce3 operon and the enzymes implicated in the
      modification of the Mce3-transported substrates.

PMID- 19389782
TI  - Role of Vfr in regulating exotoxin A production by Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa exotoxin A (ETA) production depends on the virulence
      factor regulator Vfr. Recent evidence indicates that the P. aeruginosa iron
      starvation sigma factor PvdS also enhances ETA production through the ETA
      regulatory gene regA. Mutants defective in vfr, regA and pvdS, plasmids that
      overexpress these genes individually and lacZ transcriptional/translational
      fusion plasmids were utilized to examine the relationship between vfr, regA and
      pvdS in regulating P. aeruginosa ETA production. ETA concentration and regA
      expression were reduced significantly in PAODeltavfr, but pvdS expression was not
      affected. Overexpression of Vfr produced a limited increase in ETA production in
      PAODeltapvdS, but not PAODeltaregA. Additionally, overexpression of either RegA
      or PvdS did not enhance ETA production in PAODeltavfr. RT-PCR analysis showed
      that iron did not affect the accumulation of vfr mRNA in PAO1. These results
      suggest that: (i) Vfr enhances toxA expression in PAO1 both directly and
      indirectly through regA, but not through pvdS; (ii) vfr expression is not
      regulated by iron; and (iii) both Vfr and PvdS cooperate in the presence of RegA
      to achieve a maximum level of toxA expression.

PMID- 19389783
TI  - Detection of Mycobacterium tuberculosis complex organisms in the stools of
      patients with pulmonary tuberculosis.
AB  - The laboratory diagnosis of pulmonary tuberculosis mainly relies on the detection
      of Mycobacterium tuberculosis complex (MTC) organisms in the sputum. In patients
      who do not give sputum, alternative respiratory tract specimens can be obtained
      only by invasive procedures. Based on the known survival of MTC organisms in the
      gastric fluid, we hypothesized that swallowed MTC organisms would be detectable
      in stool samples. We compared the presence of MTC organisms in respiratory tract
      specimens and stool specimens collected in parallel from the same patients. MTC
      was detected in cultures grown on egg-based medium after appropriate
      decontamination, by microscopic examination after Ziehl-Neelsen staining and by
      real-time PCR detection of IS6110 using internal controls. A case of pulmonary
      tuberculosis was defined by the presence of (i) clinical and radiological signs
      and symptoms suggestive of pulmonary tuberculosis, and (ii) culture of MTC
      organisms from at least one respiratory tract specimen or (iii) the presence of
      acid-fast bacilli in the sputum that were subsequently identified as MTC
      organisms by real-time PCR. The observation of 134 patients suspected to be
      suffering pulmonary tuberculosis led to the identification of 24 cases and 110
      non-infected control patients. Cases and controls did not significantly differ
      with respect to sex but cases were significantly younger than controls. The
      sensitivity/specificity was 37.5%/100% for the microscopic examination of stools,
      54.2%/100% for culturing and 100%/97.3% for real-time PCR. The positive predicted
      value was 100%, 100% and 88.9%, respectively, and the negative predicted value
      was 88%, 90.9% and 100%, respectively. In four patients, a stool specimen
      initially yielded the correct diagnosis of pulmonary tuberculosis before
      evaluation of the respiratory tract specimen confirmed the diagnosis. These data
      indicate that stools could be used in conjunction with sputum testing or as an
      alternative specimen upon which to base the diagnosis of pulmonary tuberculosis
      by molecular identification of acid-fast bacilli and culture. This non-invasive
      alternative procedure is of particular interest for patients who cannot
      expectorate.

PMID- 19389784
TI  - Functional characterization of the first two actinomycete 4-amino-4
      deoxychorismate lyase genes.
AB  - In some antibiotic producers, p-aminobenzoic acid (PABA) or its immediate
      precursor, 4-amino-4-deoxychorismate (ADC), is involved in primary metabolism and
      antibiotic biosynthesis. In Streptomyces sp. FR-008, a gene pabC-1 putatively
      encoding a fold-type IV pyridoxal 5'-phosphate (PLP)-dependent enzyme was found
      within the antibiotic FR-008/candicidin biosynthetic gene cluster, whose
      inactivation significantly reduced the productivity of antibiotic FR-008 to about
      20% of the wild-type level. Its specific role in PABA formation was further
      demonstrated by the successful complementation of an Escherichia coli pabC
      mutant. Moreover, a free-standing gene pabC-2, probably encoding another fold
      type IV PLP-dependent enzyme, was cloned from the same strain. Inactivation of
      pabC-2 reduced antibiotic FR-008 yield to about 57% of the wild-type level in the
      mutant, and the complementation of the E. coli pabC mutant established its
      involvement in PABA biosynthesis. Furthermore, a pabC-1/pabC-2 double mutant only
      retained about 4% of the wild-type antibiotic FR-008 productivity, clearly
      indicating that pabC-2 also contributed to biosynthesis of this antibiotic.
      Surprisingly, apparently retarded growth of the double mutant was observed on
      minimal medium, which suggested that both pabC-1 and pabC-2 are involved in PABA
      biosynthesis for primary metabolism. Finally, both PabC-1 and PabC-2 were shown
      to be functional ADC lyases by in vitro enzymic lysis with the release of
      pyruvate. pabC-1 and pabC-2 appear to represent the first two functional ADC
      lyase genes identified in actinomycetes. The involvement of these two ADC lyase
      genes in both cell growth and antibiotic FR-008 biosynthesis sets an example for
      the interplay between primary and secondary metabolisms in bacteria.

PMID- 19389786
TI  - Validation of partial rpoB gene sequence analysis for the identification of
      clinically important and emerging Acinetobacter species.
AB  - Bacteria belonging to the genus Acinetobacter are ubiquitous in soil and water.
      Only a few species, including Acinetobacter baumannii, and the unnamed
      Acinetobacter genomic species (gen. sp.) 3 and 13TU, which together with the soil
      organism Acinetobacter calcoaceticus are combined in the A. calcoaceticus-A.
      baumannii (Acb) complex, have been recognized as important nosocomial infectious
      agents. The ecology, epidemiology and pathology of most species are not yet well
      established. Lack of practical and accurate methods limits routine identification
      of clinical isolates and thus hampers precise identification of those of the Acb
      complex and other Acinetobacter species of possible clinical significance. We
      previously identified a 350 bp highly variable zone on the rpoB gene which
      appeared to be a promising target for rapid molecular identification. In the
      present study, we validated this method for accuracy on a collection of reference
      strains belonging to A. calcoaceticus (5 strains), Acinetobacter gen. sp. 3 (29
      strains), A. gen. sp. 13TU (18 strains), A. baumannii (30 strains) and one strain
      each of A. radioresistens, A. gen. sp. 15TU, A. gen. sp. 10, A. gen. sp. 11, A.
      gen. sp. 'between 1 and 3' and A. gen. sp. 14TU=13BJ. This represents the largest
      analysis to date that compares a large number of well-identified strains of the
      Acb complex to assess the intra- and interspecies variation within this complex.
      All were correctly identified with 98.9-100 % intraspecies relatedness based on
      partial rpoB sequence analysis. We then applied this tool to identify 99
      Acinetobacter clinical isolates from four public hospitals in Marseille, France.
      All isolates could easily be identified to species as they were separated into 13
      species sequence types with a sequence variance of 0-2.6% from their respective
      type strains. Of these 99 isolates, 10 were A. haemolyticus, 52 were A.
      baumannii, 27 were A. gen. sp. 3, 5 were A. schindleri, 1 was A. lwoffii, and 1
      was A. gen. sp. 13TU. Three were provisionally identified as A. gen. sp. 9. This
      is the first work to identify all specimens of a set of clinical Acinetobacter
      isolates at species level using rpoB sequence analysis. Our data emphasize the
      recognition of A. schindleri as an emerging cause of Acinetobacter-related
      infection and confirm that A. gen. sp. 3 is the second most commonly isolated
      Acinetobacter species after A. baumannii in patients.

PMID- 19389785
TI  - Expression of the sarA family of genes in different strains of Staphylococcus
      aureus.
AB  - Expression of genes involved in the pathogenesis of Staphylococcus aureus is
      controlled by global regulatory loci, including two-component regulatory systems
      and transcriptional regulators. The staphylococcal-specific SarA family of
      transcription regulators control large numbers of target genes involved in
      virulence, autolysis, biofilm formation, stress responses and metabolic
      processes, and are recognized as potential therapeutic targets. Expression of
      some of these important regulators has been examined, mostly in laboratory
      strains, while the pattern of expression of these genes in other strains,
      especially clinical isolates, is largely unknown. In this report, a comparative
      analysis of 10 sarA-family genes was conducted in six different S. aureus
      strains, including two laboratory (RN6390, SH1000) and four clinical (MW2,
      Newman, COL and UAMS-1) strains, by Northern and Western blot analyses.
      Transcription of most of the sarA-family genes showed a strong growth phase
      dependence in all strains tested. Among these genes, no difference was observed
      in expression of the sarA, sarV, sarT and sarU genes, while a major difference
      was observed in expression of the sarX gene only in strain RN6390. Expression of
      mgrA, rot, sarZ, sarR and sarS was observed in all strains, but the level of
      expression varied from strain to strain.

PMID- 19389787
TI  - Renal and cardiac function for long-term (10 year) risk stratification after
      myocardial infarction.
AB  - Aims To determine whether combined renal and cardiac function after acute
      myocardial infarction (MI) predicts 10 year mortality and heart failure (HF).
      Methods and results Estimated glomerular filtration rate (eGFR), plasma amino
      terminal pro-brain natriuretic peptide (NT-proBNP), and radionuclide
      ventriculography were obtained in 1063 patients with MI between 24-96 h of
      symptom onset. Mortality and HF were documented over follow-up of 9.3 years.
      Estimated GFR, NT-proBNP, and left ventricular ejection fraction (LVEF) each
      independently predicted 10 year mortality. Reduced eGFR (below 60 mL/min/1.73
      m(2)) combined with increased NT-proBNP (above 1000 pg/mL) was associated with
      higher mortality rate compared with preserved eGFR together with lower NT-proBNP
      (60 vs. 14%, P < 0.001). Similar results for mortality were identified for eGFR
      combined with LVEF (dichotomized about 50%) (58 vs. 17%, P < 0.001).
      Corresponding analysis combining eGFR and NT-proBNP to predict HF yielded rates
      of 34 and 7% for high- and low-risk groups, respectively (P < 0.001). Similar
      risk stratification for HF was observed when combining eGFR with LVEF (35 vs. 7%,
      P < 0.001). Conclusion Ten year rates of mortality and HF are 5-10 times higher
      when lower eGFR is present together with increased NT-proBNP or depressed LVEF.

PMID- 19389788
TI  - Immunohistological basis of the late gadolinium enhancement phenomenon in tako
      tsubo cardiomyopathy.
AB  - AIMS: Tako-tsubo cardiomyopathy is characterized by transient contractile
      dysfunction after emotional or physical stress. Only few patients show late
      gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (MRI).
      It was the purpose of this study to elucidate the histological basis of this
      phenomenon. METHODS AND RESULTS: The study included 15 patients. Tako-tsubo
      cardiomyopathy was diagnosed by coronary angiography and ventriculography.
      Cardiac MRI was performed within 24 h of admission. Endomyocardial biopsies were
      taken during the acute phase and after recovery. The content of fibrosis was
      determined by immunohistochemical staining of collagen-1. In the acute phase,
      cardiac MRI revealed LGE in five patients. This was completely reversed at follow
      up [14, inter-quartile range (IQR) 11-14.5 days]. All patients showed a
      significant increase of collagen-1 compared with control tissue. Moreover, the
      amount of collagen-1 was significantly higher in LGE positive patients (LGE
      positive: 18.84, IQR 13.82-19.75 AU/microm(2); LGE negative: 7.57, IQR 5.41-9.19
      AU/microm(2), P = 0.001). The presence of LGE was not associated with poorer left
      ventricular function. CONCLUSION: The presence of LGE cannot rule out tako-tsubo
      cardiomyopathy. Instead it defines a special subgroup of patients with a
      disproportionate increase of extracellular matrix.

PMID- 19389789
TI  - Premature foetal closure of the arterial duct: clinical presentations and
      outcome.
AB  - AIMS: The prevalence of intra-uterine ductal dysfunction is unknown and the
      clinical consequences are poorly understood. The aim of this study was to
      investigate the echocardiographic (ECHO) abnormalities and outcomes of this rare
      phenomenon. METHODS AND RESULTS: Retrospective analysis of foetal (n = 602) and
      neonatal ECHO databases (n = 1477) between 1998 and 2007. Clinical and imaging
      studies were reviewed for pathology due to or associated with premature closure
      of the duct. Twelve cases were identified. Eight (1.3%) were diagnosed pre
      natally at a median gestational age of 29.0 weeks (range: 20.0-37.5 weeks). Four
      neonates (0.3%) with significant cyanosis and absence of the arterial duct were
      also included. The most common ECHO features were: excessive right ventricular
      (RV) hypertrophy (100%), more than expected tricuspid and pulmonary regurgitation
      (100% and 92%, respectively), and right atrial dilation (75%). Premature
      induction of delivery was advised for five patients. Neonatal therapy consisted
      of observation and oxygen administration (n = 7), ventilation with pulmonary
      vasodilators (n = 5), and one required extracorporeal membrane oxygenation. There
      were three deaths due to respiratory failure with severe pulmonary hypertension.
      During follow-up, two children required additional right heart procedures and one
      developed a non-compaction cardiomyopathy. CONCLUSION: Foetal premature closure
      of the arterial duct causes stress at different foetal ages and many different
      levels of the right heart and pulmonary circulation, resulting in a wide range of
      secondary pathology. Disproportionate RV hypertrophy is the most common finding.
      Clinical outcomes range from mild symptomatology to lethal respiratory
      insufficiency.

PMID- 19389790
TI  - Effect of revascularizing viable myocardium on left ventricular diastolic
      function in patients with ischaemic cardiomyopathy.
AB  - AIMS: In patients with ischaemic left ventricular (LV) dysfunction and viable
      myocardium, revascularization improves systolic function. Diastolic dysfunction
      is also present in such patients; however, whether revascularization improves
      diastolic function also is largely unknown. METHODS: Twenty-six patients with
      chronic ischaemic cardiomyopathy [ejection fraction (EF) 32 +/- 6%, wall motion
      score index (WMSI) 2.45 +/- 0.33] and viable myocardium (low-dose dobutamine
      echocardiography) were examined at baseline and > or =4 months after
      revascularization. Diastolic function was assessed by transmitral pulsed-wave
      Doppler and tissue Doppler imaging (TDI) at the mitral annulus. RESULTS: At
      baseline, 62% of patients showed non-restrictive filling (non-RF) pattern, and
      38% restrictive filling (RF) pattern. After revascularization, along with
      improvement in systolic function (EF 43 +/- 10%, WMSI 1.78 +/- 0.47, P = 0.0002
      for both), diastolic filling improved in most patients, with only three patients
      still exhibiting RF pattern (P = 0.016); furthermore, E' velocity increased (32
      +/- 42%, P = 0.0028) and E/E' decreased (-19 +/- 31%, P = 0.0378) compared with
      baseline. Left ventricular filling pressure also decreased, from 17.5 +/- 6.8 to
      13.1 +/- 6.5 mmHg (P = 0.005). Improvement of diastolic function by TDI was
      related to the extent of viability at baseline (P = 0.0098) and to LV reverse
      remodelling after revascularization (P = 0.0092). CONCLUSION: In patients with
      ischaemic cardiomyopathy, LV diastolic filling may largely improve after
      revascularization. Improvement of diastolic dysfunction is related to the amount
      of viable tissue and it may represent an additional advantage of revascularizing
      dyssinergic but viable myocardium.

PMID- 19389791
TI  - Use of the left coronary sinus of Valsalva for left anterior accessory pathway
      catheter ablation.
AB  - We report our experience regarding a case of left anterior accessory pathway
      (LAAP) catheter ablation, which finally required a retrograd approach via the
      left coronary sinus of Valsalva. Because of its relationship with small regions
      of myocardium, the sinus of Valsalva might be an important route of access during
      some catheter ablation procedures. Rares publications have emphasized the
      importance of sinus of Valsalva for LAAP ablation. Our case shows the importance
      of carefully mapping the whole sinus of Valsalva in cases when ablation sites are
      difficult to access or are unstable via trans-aortic and transseptal approaches.
      We also discuss the proximity of the main left coronary artery, which requires
      particular attention and the need to perform coronary angiography before
      ablation.

PMID- 19389792
TI  - Test-retest reliability and minimal detectable change scores for the timed "up &
      go" test, the six-minute walk test, and gait speed in people with Alzheimer
      disease.
AB  - BACKGROUND: With the increasing incidence of Alzheimer disease (AD), determining
      the validity and reliability of outcome measures for people with this disease is
      necessary. OBJECTIVE: The goals of this study were to assess test-retest
      reliability of data for the Timed "Up & Go" Test (TUG), the Six-Minute Walk Test
      (6MWT), and gait speed and to calculate minimal detectable change (MDC) scores
      for each outcome measure. Performance differences between groups with mild to
      moderate AD and moderately severe to severe AD (as determined by the Functional
      Assessment Staging [FAST] scale) were studied. DESIGN: This was a prospective,
      nonexperimental, descriptive methodological study. METHODS: Background data
      collected for 51 people with AD included: use of an assistive device, Mini-Mental
      Status Examination scores, and FAST scale scores. Each participant engaged in 2
      test sessions, separated by a 30- to 60-minute rest period, which included 2 TUG
      trials, 1 6MWT trial, and 2 gait speed trials using a computerized gait
      assessment system. A specific cuing protocol was followed to achieve optimal
      performance during test sessions. RESULTS: Test-retest reliability values for the
      TUG, the 6MWT, and gait speed were high for all participants together and for the
      mild to moderate AD and moderately severe to severe AD groups separately
      (intraclass correlation coefficients > or = .973); however, individual
      variability of performance also was high. Calculated MDC scores at the 90%
      confidence interval were: TUG=4.09 seconds, 6MWT=33.5 m (110 ft), and gait
      speed=9.4 cm/s. The 2 groups were significantly different in performance of
      clinical tests, with the participants who were more cognitively impaired being
      more physically and functionally impaired. LIMITATIONS: A single researcher for
      data collection limited sample numbers and prohibited blinding to dementia level.
      CONCLUSIONS: The TUG, the 6MWT, and gait speed are reliable outcome measures for
      use with people with AD, recognizing that individual variability of performance
      is high. Minimal detectable change scores at the 90% confidence interval can be
      used to assess change in performance over time and the impact of treatment.

PMID- 19389793
TI  - Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo
      controlled trial.
AB  - BACKGROUND: Uterine leiomyomas are widely prevalent and frequently cause
      menorrhagia. The major therapeutic option today is hysterectomy. Medical options
      are of highest interest. METHODS: A total of 30 women with uterine leiomyomas
      scheduled for surgical intervention were randomized to receive either 50 mg
      mifepristone or placebo every other day during 3 months prior to surgery. Uterine
      blood flow and leiomyoma volume were evaluated once a month until surgery.
      Endometrial biopsies were obtained prior to and at end of treatment. Relevant
      biochemistry, symptoms and bleeding were recorded. Primary outcome was reduction
      in uterine leiomyoma size. RESULTS: There was a significant percentual decrease
      (P = 0.021) in the total leiomyoma volume in the mifepristone-treated group, -28
      (-48, -8) % (mean +/- 0, 95 confidence interval), compared with the control group
      values 6 (-13, 25) %. Mifepristone treatment significantly reduced the bleeding
      days (P = 0.001) and increased serum haemoglobin values (P = 0.046). Serum
      cortisol levels remained unchanged, while a mild increase in serum androgens was
      noted. Endometrial biopsies showed no premalignant changes or changes in mitotic
      indices. CONCLUSION: Mifepristone may offer an effective treatment option for
      women with uterine leiomyoma and the associated pronounced uterovaginal bleeding.
      Clinical Trials identifier: www.clinicaltrials.gov: NCT00579475.

PMID- 19389794
TI  - Retrospective review of surgery and definitive chemoradiotherapy in patients with
      squamous cell carcinoma of the thoracic esophagus aged 75 years or older.
AB  - OBJECTIVE: The aim of this study was to review the treatment outcomes of surgery
      and definitive chemoradiotherapy (CRT) in elderly patients with squamous cell
      carcinoma of the thoracic esophagus. METHODS: A total of 64 patients aged 75 or
      older were retrospectively reviewed; 40 were treated with surgery and 24 with
      CRT. The CRT group included eight patients with unresectable disease and four
      patients medically unfit for surgery. Surgery included esophagectomy with
      lymphadenectomy and CRT consisted of 60-70 Gy of radiation concurrent with 5
      fluorouracil alone or combined with cisplatin. Short- and long-term outcomes and
      survival of each modality were assessed. RESULTS: In the surgery group, 33
      patients (82.5%) had co-morbid conditions. Complete resection rate was 90.0%. An
      overall post-operative complication rate was 65.0% and in-hospital mortality was
      seen in three patients (7.5%). In the CRT group, complete response rate was
      41.7%. Leukopenia was most common Grade 3 hematological toxicity. Treatment
      related deaths caused by acute toxicities occurred in three patients (12.5%),
      whereas those caused by late toxicities in four (16.7%). For cStage I disease in
      the surgery group, the overall 1-, 3- and 5-year survival rate were 90.9%, 63.6%
      and 54.5%, respectively, with a median survival time of 78.7 months. For cStages
      II-IV, the median survival time of the surgery and the CRT group was 18.7 and
      12.8 months, respectively. CONCLUSIONS: The short- and long-term outcomes of
      surgery for the elderly seemed acceptable; however, definitive CRT may be a
      promising treatment modality. Further investigation may alter the sphere of
      influence in the field of esophageal cancer treatment in the elderly.

PMID- 19389795
TI  - A randomized phase II/III trial comparing hepatectomy followed by mFOLFOX6 with
      hepatectomy alone as treatment for liver metastasis from colorectal cancer: Japan
      Clinical Oncology Group Study JCOG0603.
AB  - A randomized controlled trial is being conducted in Japan to compare hepatectomy
      alone with hepatectomy followed by adjuvant chemotherapy as treatment in patients
      with curatively resected liver metastases from colorectal cancer to improve
      survival with intensive chemotherapy. Between 42 and 70 days after liver
      resection, patients are randomly assigned to either hepatectomy alone or
      hepatectomy followed by 12 cycles of modified FOLFOX6 (mFOLFOX6) regimen. A total
      of 300 patients (including 78 patients in Phase II) will be accrued from 38
      institutions within 3 years. The primary endpoint is treatment compliance at nine
      courses of mFOLFOX6 regimen in Phase II and disease-free survival in Phase III.
      The secondary endpoints are overall survival, incidence of adverse events and
      patterns of recurrence.

PMID- 19389796
TI  - Cellular expression and antimicrobial function of a phylogenetically conserved
      novel histone 1x-like protein on mouse cells: a potential new class of pattern
      recognition receptor.
AB  - A H1x-like protein (i.e., NCAMP-1) is expressed on the membrane and in GEs from
      fish NK-like cells. In the present study, we identify the imprinting control
      region mouse NCAMP-1 ortholog using NCAMP-1 polyclonal antibodies and mAb.
      Polychromatic flow cytometry revealed NCAMP-1 expression on PBLs (Gr-1(+) PMNs
      were 21.1% NCAMP-1(+); DX-5(+) NK cells were 12.2% NCAMP-1(+)), mesenteric LN
      cells (CD11c(+) DCs were 23.2% NCAMP-1(+); Gr-1(+) PMNs were 24.8% NCAMP-1(+);
      CD21(+) B cells were 17.8% NCAMP-1(+)), and splenocytes (CD11c(+) were 39.6%
      NCAMP-1(+); Gr-1(+) PMNs were 40.9% NCAMP-1(+); DX-5(+) NK cells were 24.3% NCAMP
      1(+); CD21(+) B cells were 28.5% NCAMP-1(+)). Western blot analysis using pNCAMP
      1 and GEs from RAW 264.7 cells produced a 32-kDa signal. GEs from RAW 264.7 cells
      produced a significant reduction in Escherichia coli CFU. This antimicrobial
      killing activity was inhibited by pretreatment of the extract with (polyclonal)
      anti-NCAMP-1. Treatment with preimmune serum did not reduce bacterial cell
      killing. Confocal microscopy using NCAMP-1 and LAMP-1 mAb demonstrated that NCAMP
      1 was located on the membrane and in cytosolic vesicles of RAW 264.7 cells and
      did not appear to colocalize with LAMP-1. NCAMP-1 may participate as a
      bifunctional protein on cells. It is expressed on the membranes of phagocytic
      cells, NK cells, and APCs in mice as well as in the granules of macrophages. In
      phagocytic cells, NCAMP-1 may participate in a nonregulated exocytosis pathway of
      cellular secretion.

PMID- 19389797
TI  - IL-15 protects antigen-specific CD8+ T cell contraction after Mycobacterium bovis
      bacillus Calmette-Guerin infection.
AB  - We reported previously that IL-15 plays a critical role in protecting effector
      CD8(+) T cells from apoptosis during the contraction phase following acute
      infection with Listeria monocytogenes by inducing antiapoptotic molecules. In the
      present study, we examined the effects of in vivo administration of rIL-15 on
      contraction of CD8(+) T cells after chronic infection with Mycobacterium bovis
      BCG and on the efficacy of BCG vaccination against Mycobacterium tuberculosis
      infection. Antigen-specific CD8(+) T cells reached an expansion peak at
      approximately Day 21, followed by a contraction after inoculation with rBCG
      expressing OVA. In vivo administration of rIL-15 from Days 22 to 42 after BCG
      inoculation inhibited apoptosis of effector CD8(+) T cells by up-regulating their
      Bcl-2 expression, resulting in a significant increase of antigen-specific memory
      CD8(+) T cells producing IFN-gamma. However, the IL-15 treatment did not elicit
      improved efficacy of BCG vaccination against M. tuberculosis. These results
      suggest that IL-15 plays a critical role in protecting activated CD8(+) T cells
      from apoptosis during the contraction phase following BCG inoculation, although
      IL-15 administration alone at the contraction phase might not be sufficient to
      protect the efficient memory T cell responses against subsequent infection with
      M. tuberculosis.

PMID- 19389799
TI  - Activation of PPARbeta/delta inhibits leukocyte recruitment, cell adhesion
      molecule expression, and chemokine release.
AB  - The infiltration of PMNs into tissues is a prominent feature in inflammation. The
      mechanism underlying PMN recruitment depends on the release of chemotactic
      mediators and CAM expression on endothelial cells. The nuclear receptor
      PPARbeta/delta is widely expressed in many tissues, including the vascular
      endothelium; however, its role in acute inflammation remains unclear. Using
      intravital microscopy in the mouse cremasteric microcirculation, we have shown
      that activation of PPARbeta/delta by its selective ligand GW501516 inhibits TNF
      alpha-induced leukocyte rolling flux, adhesion, and emigration in a dose
      dependant manner. Moreover, GW501516 reduced the expression of adhesion molecules
      such as ICAM-1, VCAM-1, and E-selectin in the cremasteric postcapillary venules.
      Similarly, rolling and adhesion of hPMNs under physiological flow on TNF-alpha
      activated HUVECs were also inhibited markedly by GW501516. These inhibitory
      responses of GW501516 on activated endothelium were accompanied by a reduction in
      TNF-alpha-induced endothelial GRO-alpha release and VCAM-1, E-selectin, and ICAM
      1 mRNA expression. Taken together, our results show that PPARbeta/delta modulates
      acute inflammation in vivo and in vitro under flow by targeting the neutrophil
      endothelial cell interaction.

PMID- 19389798
TI  - Coregulation in human leukocytes of the long pentraxin PTX3 and TSG-6.
AB  - The prototypic long PTX3 is a multifunctional protein involved in innate
      resistance to pathogens and in controlling inflammation. TSG-6 is a hyaluronan
      binding protein that is involved in ECM remodeling and has anti-inflammatory and
      chondroprotective functions. PTX3 and TSG-6 are coregulated by growth
      differentiation factor-9 in granulosa cells, where they are produced during the
      periovulatory period and play essential roles in the incorporation of hyaluronan
      into the ECM during cumulus expansion. The present study was designed to assess
      whether PTX3 and TSG-6 are coregulated in leukocytes, in particular, in
      phagocytes and DC. Monocytes, macrophages, and myeloid DC were found to produce
      high levels of TSG-6 and PTX3 in response to proinflammatory mediators (LPS or
      cytokines). Unstimulated neutrophil polymorphonuclear granulocytes expressed high
      levels of TSG-6 mRNA, but not PTX3 transcript, and stored both proteins in
      granules. In contrast, endothelial cells expressed substantial amounts of PTX3
      mRNA and low levels of TSG-6 transcript under the conditions tested. Anti
      inflammatory cytokines, such as IL-4, dampened LPS-induced TSG-6 and PTX3
      expression. Divergent effects were observed with IL-10, which synergizes with TLR
      mediated PTX3 induction but inhibits LPS-induced TSG-6 transcription.
      Immunohistochemical analysis confirms the colocalization of the two proteins in
      inflammatory infiltrates and in endothelial cells of inflamed tissues. Thus, here
      we show that myelomonocytic cells and MoDC are a major source of TSG-6 and that
      PTX3 and TSG-6 are coregulated under most of the conditions tested. The
      coordinated expression of PTX3 and TSG-6 may play a role in ECM remodeling at
      sites of inflammation.

PMID- 19389800
TI  - Neutrophils rescue gingival epithelial cells from bacterial-induced apoptosis.
AB  - In the pathogenesis of chronic inflammatory periodontal disease, neutrophils are
      recognized as a major cellular component from the histopathology of the
      periodontal lesion around teeth and from clinical cases where absence or
      dysfunction of neutrophils results in major periodontal destruction. Neutrophils
      are recruited in vast numbers into the gingival crevice during periodontal
      inflammation, attracted by microbial plaque chemoattractants and chemokines
      released following microbial perturbation of gingival epithelial cells.
      Porphyromonas gingivalis, a major periodontopathogen, triggers a vast array of
      cellular responses in gingival epithelial cells but also induces apoptosis. We
      demonstrate here that neutrophils, when combined in a P. gingivalis challenge
      assay of epithelial cells, prevent epithelial cell apoptosis by phagocytosing P.
      gingivalis and later undergoing apoptosis themselves. By removing P. gingivalis
      by phagocytosis, neutrophils also protect the host from the harmful effects of
      its microbial proteases, which degrade inflammatory cytokines and other host
      molecules.

PMID- 19389801
TI  - Hepatic bile acid metabolism in the neonatal hamster: expansion of the bile acid
      pool parallels increased Cyp7a1 expression levels.
AB  - Intraluminal concentrations of bile acids are low in newborn infants and increase
      rapidly after birth, at least partly owing to increased bile acid synthesis
      rates. The expansion of the bile acid pool is critical since bile acids are
      required to stimulate bile flow and absorb lipids, a major component of newborn
      diets. The purpose of the present studies was to determine the mechanism
      responsible for the increase in bile acid synthesis rates and the subsequent
      enlargement of bile acid pool sizes (BAPS) during the neonatal period, and how
      changes in circulating hormone levels might affect BAPS. In the hamster, pool
      size was low just after birth and increased modestly until 10.5 days postpartum
      (dpp). BAPS increased more significantly ( approximately 3-fold) between 10.5 and
      15.5 dpp. An increase in mRNA and protein levels of cholesterol 7alpha
      hydroxylase (Cyp7a1), the rate-limiting step in classical bile acid synthesis,
      immediately preceded an increase in BAPS. In contrast, levels of oxysterol 7alpha
      hydroxylase (Cyp7b1), a key enzyme in bile acid synthesis by the alternative
      pathway, were relatively elevated by 1.5 dpp. farnesyl X receptor (FXR) and short
      heterodimeric partner (SHP) mRNA levels remained relatively constant at a time
      when Cyp7a1 levels increased. Finally, although simultaneous increases in
      circulating cortisol and Cyp7a1 levels occurred, precocious expression of Cyp7a1
      could not be induced in neonatal hamsters with dexamethasone. Thus the
      significant increase in Cyp7a1 levels in neonatal hamsters is due to mechanisms
      independent of the FXR and SHP pathway and cortisol.

PMID- 19389802
TI  - HCl-activated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal
      mucosa.
AB  - To test whether transient receptor potential channel vanilloid subfamily member-1
      (TRPV1) mediates acid-induced inflammation in the esophagus, a tubular segment of
      esophageal mucosa was tied at both ends, forming a sac. The sac was filled with
      0.01 N HCl (or Krebs buffer for control) and kept in oxygenated Krebs buffer at
      37 degrees C. The medium around the sac (supernatant) was collected after 3 h.
      Supernatant of the HCl-filled sac abolished contraction of esophageal circular
      muscle strips in response to electric field stimulation. Contraction was
      similarly abolished by supernatant of mucosal sac filled with the TRPV1 agonist
      capsaicin (10(-6) M). These effects were reversed by the selective TRPV1
      antagonist 5'-iodoresiniferatoxin (IRTX) and by the platelet-activating factor
      (PAF) receptor antagonist CV9388. Substance P and CGRP levels in mucosa and in
      supernatant increased in response to HCl, and these increases were abolished by
      IRTX and by tetrodotoxin (TTX) but not affected by CV9388, indicating that
      substance P and CGRP are neurally released and PAF independent. In contrast, the
      increase in PAF was blocked by IRTX but not by TTX. Presence of TRPV1 receptor
      was confirmed by RT-PCR and by Western blot analysis in whole mucosa and in
      esophageal epithelial cells enzymatically isolated and sorted by flow cytometry
      or immunoprecipitated with cytokeratin antibodies. In epithelial cells PAF
      increased in response to HCl, and the increase was abolished by IRTX. We conclude
      that HCl-induced activation of TRPV1 receptors in esophageal mucosa causes
      release of substance P and CGRP from neurons and release of PAF from epithelial
      cells.

PMID- 19389803
TI  - Molecular and functional characterization of Kv7 K+ channel in murine
      gastrointestinal smooth muscles.
AB  - Members of the K(v)7 voltage-gated K(+) channel family are important determinants
      of cardiac and neuronal membrane excitability. Recently, we and others have shown
      that K(v)7 channels are also crucial regulators of smooth muscle activity. The
      aim of the present study was to assess the K(v)7 expression in different parts of
      the murine gastrointestinal (GI) tract and to assess their functional roles by
      use of pharmacological agents. Of KCNQ/K(v)7 members, both KCNQ4/K(v)7.4 and
      KCNQ5/K(v)7.5 genes and proteins were the most abundantly expressed K(v)7
      channels in smooth muscles throughout the GI tract. Immunohistochemical staining
      also revealed that K(v)7.4 and K(v)7.5 but not K(v)7.1 were expressed in the
      circular muscle layer of the colon. In segments of distal colon circular muscle
      exhibiting spontaneous phasic contractions, the nonselective K(v)7 blockers XE991
      and linopirdine increased the integral of tension. Increases in the integral of
      tension were also observed under conditions of neuronal blockade. Similar
      effects, although less marked, were observed in the proximal colon. As expected,
      the K(v)7.1-selective blocker chromanol 293B had no effect in either type of
      segment. These data show that K(v)7.x especially K(v)7.4 and K(v)7.5 are
      expressed in different regions of the murine gastrointestinal tract and blockers
      of K(v)7 channels augment inherent contractile activity. Drugs that selectively
      block K(v)7.4/7.5 might be promising therapeutics for the treatment of motility
      disorders such as constipation associated with irritable bowel syndrome.

PMID- 19389805
TI  - Hepatocyte nuclear factor 4alpha contributes to an intestinal epithelial
      phenotype in vitro and plays a partial role in mouse intestinal epithelium
      differentiation.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) is a regulator of hepatocyte and
      pancreatic transcription. Hnf4alpha deletion in the mouse is embryonically lethal
      with severe defects in visceral endoderm formation. It has been concluded in the
      past that the role of Hnf4alpha in the developing colon was much less important
      than in the liver. However, the precise role of Hnf4alpha in the homeostasis of
      the small intestinal epithelium remains unclear. Our aim was to evaluate the
      potential of Hnf4alpha to support an intestinal epithelial phenotype. First,
      Hnf4alpha potential to dictate this phenotype was assessed in nonintestinal cell
      lines in vitro. Forced expression of Hnf4alpha in fibroblasts showed an induction
      of features normally restricted to epithelial cells. Combinatory expression of
      Hnf4alpha with specific transcriptional regulators of the intestine resulted in
      the induction of intestinal epithelial genes in this context. Second, the
      importance of Hnf4alpha in maintaining the homeostasis of the intestinal
      epithelium was investigated in mice. Mice conditionally deficient for intestinal
      Hnf4alpha developed normally throughout adulthood with an epithelium displaying
      normal morphological and functional structures with minor alterations. Subtle but
      statistical differences were observed at the proliferation and the
      cytodifferentiation levels. Hnf4alpha mutant mice displayed an increase in the
      number of goblet and enteroendocrine cells compared with controls. Given the
      fundamental role of this transcription factor in other tissues, these findings
      dispute the crucial role for this regulator in the maintenance of intestinal
      epithelial cell function at a period of time that follows cytodifferentiation but
      may suggest a functional role in instructing cells to become specific to the
      intestinal epithelium.

PMID- 19389804
TI  - Follicle-stimulating hormone increases cholangiocyte proliferation by an
      autocrine mechanism via cAMP-dependent phosphorylation of ERK1/2 and Elk-1.
AB  - Sex hormones regulate cholangiocyte hyperplasia in bile duct-ligated (BDL) rats.
      We studied whether follicle-stimulating hormone (FSH) regulates cholangiocyte
      proliferation. FSH receptor (FSHR) and FSH expression was evaluated in liver
      sections, purified cholangiocytes, and cholangiocyte cultures (NRICC). In vivo,
      normal female and male rats were treated with FSH or immediately after BDL with
      antide (a gonadotropin-releasing hormone antagonist blocking FSH secretion) or a
      neutralizing FSH antibody for 1 wk. We evaluated 1) cholangiocyte proliferation
      in sections and cholangiocytes and 2) changes in secretin-stimulated cAMP
      (functional index of cholangiocyte growth) levels, and ERK1/2 and Elk-1
      phosphorylation. NRICC were stimulated with FSH before evaluation of
      proliferation, cAMP/IP(3) levels, and ERK1/2 and Elk-1 phosphorylation. To
      determine whether FSH regulates cholangiocyte proliferation by an autocrine
      mechanism, we evaluated the effects of 1) cholangiocyte supernatant (containing
      FSH) on NRICC proliferation and 2) FSH silencing in NRICC before measuring
      proliferation and ERK1/2 and Elk-1 phosphorylation. Cholangiocytes and NRICC
      express FSHR and FSH and secrete FSH. In vivo administration of FSH to normal
      rats increased, whereas administration of antide and anti-FSH antibody to BDL
      rats decreased 1) ductal mass and 2) secretin-stimulated cAMP levels,
      proliferation, and ERK1/2 and Elk-1 phosphorylation in cholangiocytes compared
      with controls. In NRICC, FSH increased cholangiocyte proliferation, cAMP levels,
      and ERK1/2 and Elk-1 phosphorylation. The supernatant of cholangiocytes increased
      NRICC proliferation, inhibited by preincubation with anti-FSH antibody. Silencing
      of FSH gene decreases cholangiocyte proliferation and ERK1/2 and Elk-1
      phosphorylation. Modulation of cholangiocyte FSH expression may be important for
      the management of cholangiopathies.

PMID- 19389806
TI  - Morphological adaptation with preserved proliferation/transporter content in the
      colon of patients with short bowel syndrome.
AB  - In short bowel syndrome (SBS), although a remaining colon improves patient
      outcome, there is no direct evidence of a mucosal colonic adaptation in humans.
      This prospective study evaluates morphology, proliferation status, and
      transporter expression level in the epithelium of the remaining colon of adult
      patients compared with controls. The targeted transporters were Na+/H+ exchangers
      (NHE2 and 3) and oligopeptide transporter (PepT1). Twelve adult patients with a
      jejuno-colonic anastomosis were studied at least 2 yr after the last surgery and
      compared with 11 healthy controls. The depth of crypts and number of epithelial
      cells per crypt were quantified. The proliferating and apoptotic cell contents
      were evaluated by revealing Ki67, PCNA, and caspase-3. NHE2, NHE3, PepT1 mRNAs,
      and PepT1 protein were quantified by quantitative RT-PCR and Western blot,
      respectively. In patients with SBS compared with controls, 1) hyperphagia and
      severe malabsorption were documented, 2) crypt depth and number of cells per
      crypt were 35% and 22% higher, respectively (P < 0.005), whereas the
      proliferation and apoptotic levels per crypt were unchanged, and 3) NHE2 mRNA was
      unmodified; NHE3 mRNA was downregulated near the anastomosis and unmodified
      distally, and PepT1 mRNA and protein were unmodified. We concluded that, in
      hyperphagic patients with SBS with severe malabsorption, adaptive colonic changes
      include an increased absorptive surface with an unchanged proliferative/apoptotic
      ratio and well-preserved absorptive NHE2, NHE3, and PepT1 transporters. This is
      the first study showing a controlled nonpharmacological hyperplasia in the colon
      of patients with SBS.

PMID- 19389807
TI  - Portal pressure responses and angiotensin peptide production in rat liver are
      determined by relative activity of ACE and ACE2.
AB  - Angiotensin converting enzyme (ACE) 2 activity and angiotensin-(1-7) [Ang-(1-7)]
      levels are increased in experimental cirrhosis; however, the pathways of hepatic
      Ang-(1-7) production have not been studied. This study investigated the role of
      ACE2, ACE, and neutral endopeptidase (NEP) in the hepatic formation of Ang-(1-7)
      from angiotensin I (Ang I) and Ang II and their effects on portal resistance. Ang
      I or Ang II were administered to rat bile duct ligated (BDL) and control livers
      alone and in combination with the ACE inhibitor lisinopril, the ACE and NEP
      inhibitor omapatrilat, or the ACE2 inhibitor MLN4760 (n = 5 per group). BDL
      markedly upregulated ACE, ACE2, and NEP. Ang-(1-7) was produced from Ang II in
      healthy and in BDL livers and was increased following ACE inhibition and
      decreased by ACE2 inhibition. In contrast, Ang-(1-7) production from Ang I was
      minimal and not affected by ACE or NEP inhibition. Surprisingly, ACE2 inhibition
      in BDLs dramatically increased Ang-(1-7) production from Ang I, an effect
      abolished by ACE2/NEP inhibition. Ang II and Ang I induced greater portal
      pressure increases in BDL livers than controls. The effects of Ang I were closely
      correlated with Ang II production and were strongly attenuated by both ACE and
      ACE/NEP inhibition. These findings show that the major substrate for hepatic
      production of Ang-(1-7) is Ang II and this is catalyzed by ACE2. Ang I is largely
      converted to Ang II by ACE, and net conversion of Ang I to Ang-(1-7) is small.
      NEP has the ability to generate large amounts of Ang-(1-7) in the BDL liver from
      Ang I only when ACE2 activity is greatly decreased or inhibited.

PMID- 19389808
TI  - MBX-102/JNJ39659100, a novel peroxisome proliferator-activated receptor-ligand
      with weak transactivation activity retains antidiabetic properties in the absence
      of weight gain and edema.
AB  - MBX-102/JNJ39659100 (MBX-102) is in clinical development as an oral glucose
      lowering agent for the treatment of type 2 diabetes. MBX-102 is a
      nonthiazolidinedione (TZD) selective partial agonist of peroxisome proliferator
      activated receptor (PPAR)-gamma that is differentiated from the TZDs
      structurally, mechanistically, preclinically and clinically. In diabetic rodent
      models, MBX-102 has insulin-sensitizing and glucose-lowering properties
      comparable to TZDs without dose-dependent increases in body weight. In vitro, in
      contrast with full PPAR-gamma agonist treatment, MBX-102 fails to drive human and
      murine adipocyte differentiation and selectively modulates the expression of a
      subset of PPAR-gamma target genes in mature adipocytes. Moreover, MBX-102 does
      not inhibit osteoblastogenesis of murine mesenchymal cells. Compared with full
      PPAR-gamma agonists, MBX-102 displays differential interactions with the PPAR
      gamma ligand binding domain and possesses reduced ability to recruit
      coactivators. Interestingly, in primary mouse macrophages, MBX-102 displays
      enhanced antiinflammatory properties compared with other PPAR-gamma or
      alpha/gamma agonists, suggesting that MBX-102 has more potent transrepression
      activity. In summary, MBX-102 is a selective PPAR-gamma modulator with weak
      transactivation but robust transrepression activity. MBX-102 exhibits full
      therapeutic activity without the classical PPAR-gamma side effects and may
      represent the next generation insulin sensitizer.

PMID- 19389809
TI  - Pharmacochaperone-mediated rescue of calcium-sensing receptor loss-of-function
      mutants.
AB  - The calcium sensing receptor (CaSR) is a Family C/3 G protein-coupled receptor
      that translates changes in extracellular Ca(2+) into diverse intracellular
      signals. Loss-of-function mutations in human CaSR cause familial hypocalciuric
      hypercalcemia and neonatal severe hyperparathyroidism. CaSR must navigate a
      number of endoplasmic reticulum quality control checkpoints during biosynthesis,
      including a conformational/functional checkpoint. Here we examine the
      biosynthesis of 25 CaSR mutations causing familial hypocalciuric hypercalcemia
      /neonatal severe hyperparathyroidism using immunoprecipitation, biotinylation,
      and functional assays. We define classes of CaSR mutants based on their
      biosynthetic profile. Class I CaSR mutants are not rescued to the plasma
      membrane. To dissect the organellar compartments that class I mutants can access,
      we engineered a cleavage site for the proprotein convertase furin into the
      extracellular domain of wild-type CaSR and class I mutants. Based on absence or
      presence of cleavage fragments, we find most mutants are degraded from the
      endoplasmic reticulum (no furin-mediated cleavage), whereas others access the
      Golgi (furin-mediated cleavage) before degradation. Class II CaSR mutants show
      increased expression and/or enhanced plasma membrane localization upon treatment
      with MG132 or the pharmacochaperone NPS R-568, permitting assay of functional
      activity. Of the 10 CaSR mutants that exhibit plasma membrane localization, only
      two did not show enhanced functional activity after rescue with NPS R-568. The
      established approaches can be used with current and newly identified CaSR
      mutations to identify the location of biosynthetic block and to determine the
      likelihood of rescue by allosteric agonists.

PMID- 19389810
TI  - Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha,
      and HNF4alpha.
AB  - The transcriptional coactivator peroxisome proliferator-activated receptor-gamma
      coactivator (PGC)-1alpha is involved in the coordinate induction of changes in
      gene expression in the liver that enable a homeostatic response to alterations in
      metabolic state, environmental cues, and nutrient availability. In exploring the
      specific pathways under PGC-1alpha regulation in the liver, we have made the
      surprising observation that this coactivator can induce the expression of CYP11A1
      and CYP17A1, key rate-limiting enzymes involved in the initial steps of
      steroidogenesis. Both of these enzymes function to produce C(19)-steroids,
      converting cholesterol into pregnenolone, and then to dehydroepiandrosterone
      (DHEA). Estrogen-related receptor (ERR)-alpha mediates PGC-1alpha's induction of
      CYP11A1 and binds within the first intron of the CYP11A1 gene. Both ERR-alpha and
      hepatocyte nuclear factor-4alpha are required for PGC-1alpha-mediated induction
      of CYP17A1, and specific binding sites for these receptors have been identified
      in the regulatory regions of this gene. The potential physiological significance
      of these observations was highlighted in rats where fasting induced hepatic
      expression of PGC-1alpha and CYP17A1 and was associated with an increase in
      hepatic levels of DHEA. These data suggest that DHEA could be playing a role as
      an intracellular signaling molecule involved in modulating hepatic activity in
      response to fasting conditions.

PMID- 19389811
TI  - Repression of Runx2 by androgen receptor (AR) in osteoblasts and prostate cancer
      cells: AR binds Runx2 and abrogates its recruitment to DNA.
AB  - Runx2 and androgen receptor (AR) are master transcription factors with pivotal
      roles in bone metabolism and prostate cancer (PCa). We dissected AR-mediated
      repression of Runx2 in dihydrotestosterone (DHT)-treated osteoblastic and PCa
      cells using reporter assays and endogenous Runx2 target genes. Repression
      required DHT, but not AR's transactivation function, and was associated with
      nuclear colocalization of the two proteins. Runx2 and AR coimmunoprecipitated and
      interacted directly in glutathione-S-transferase pull-down assays. Interaction
      was ionic in nature. Intact AR DNA-binding domain (DBD) was necessary and
      sufficient for both interaction with Runx2 and its repression. Runx2 sequences
      required for interaction were the C-terminal 132 amino acid residues together
      with the Runt DBD. Runx2 DNA binding was abrogated by endogenous AR in chromatin
      immunoprecipitation assays and by recombinant AR-DBD in gel shift assays.
      Furthermore, AR caused increased nuclear mobility of Runx2 as indicated by faster
      fluorescence recovery after photobleaching. Thus, AR binds Runx2 and abrogates
      its binding to DNA and possibly to other nuclear components. Clinical relevance
      of our results was suggested by an inverse correlation between expression of AR
      responsive prostate-specific antigen and osteocalcin genes in PCa biopsies. Given
      the tumor suppressor properties of Runx2, its repression by AR may constitute a
      mechanism of hormone carcinogenesis. Attenuation of Runx2 by AR in osteoblasts
      may play a role in skeletal metabolism: the bone-sparing effect of androgens is
      attributable, in part, to keeping Runx2 activity in check and preventing high
      turnover bone disease such as seen after castration and in transgenic mice
      overexpressing Runx2 in osteoblasts.

PMID- 19389812
TI  - Mechanism of BRCA1-mediated inhibition of progesterone receptor transcriptional
      activity.
AB  - Previously, we reported that BRCA1 inhibits progesterone receptor (PR) activity
      and blocks progesterone-stimulated gene expression and cell proliferation. In the
      present manuscript, we studied the mechanism of BRCA1 inhibition of PR activity,
      using c-Myc as a model progesterone-regulated promoter. Here, we found that BRCA1
      has little or no effect on PR ligand-binding affinity. However, BRCA1
      overexpression inhibited the R5020-induced recruitment of PR to the c-Myc and
      mouse mammary tumor virus progesterone response elements (PREs) and blocked R5020
      stimulated c-Myc expression, whereas BRCA1 underexpression did the opposite. In
      EMSAs, BRCA1 overexpression blocked the R5020-induced complex formation between
      PR and several radiolabeled PRE-containing oligonucleotides, and in vitro
      translated BRCA1 blocked the interaction of full-length PR-A or a fragment
      containing the DNA-binding domain of PR with a radiolabeled PRE oligonucleotide.
      In further studies, BRCA1 overexpression inhibited the recruitment of
      coactivators (steroid receptor coactivator 1 and amplified in breast cancer 1)
      and enhanced the recruitment of a corepressor (histone deacetylase 1) to the c
      Myc PRE, whereas BRCA1 knockdown increased the abundance of AIB1 and decreased
      the abundance of HDAC1 at the c-Myc PRE. These findings suggest that BRCA1
      inhibits progestin-stimulated PR activity, in part, by preventing PR from binding
      to the PRE and by promoting the formation of a corepressor complex rather than a
      coactivator complex.

PMID- 19389813
TI  - Adiponectin and lipoprotein particle size.
AB  - OBJECTIVE: Adiponectin has been postulated to affect lipid and insulin signal
      transduction pathways. We evaluated the relationships of plasma adiponectin with
      lipoprotein mean particle size and subclass concentrations, independent of
      obesity and insulin sensitivity. RESEARCH DESIGN AND METHODS: A cross-sectional
      analysis of 884 young Israeli adults who participated in the population-based
      Jerusalem Lipid Research Clinic (LRC) study was conducted. Lipoprotein particle
      size was assessed using proton nuclear magnetic resonance. RESULTS: In
      multivariable linear regression models that included sex, BMI, waist
      circumference, homeostasis model assessment of insulin resistance, and leptin,
      adiponectin was associated with mean LDL size (standardized regression
      coefficient B = 0.20; P < 0.001), VLDL size (B = -0.12; P < 0.001), and HDL size
      (B = 0.06; P = 0.013). Adiponectin was inversely related to large VLDL (P <
      0.001) but positively to small VLDL (P = 0.02), inversely related to small LDL (P
      < 0.006) but positively to large LDL (P < 0.001), and positively related to large
      HDL (P < 0.001) subclass concentrations. CONCLUSIONS: Adiponectin is favorably
      associated with lipoprotein particle size and subclass distribution independent
      of adiposity and insulin sensitivity.

PMID- 19389814
TI  - Longitudinal analysis of depressive symptoms and glycemic control in type 2
      diabetes.
AB  - OBJECTIVE: To compare whether depressive symptoms are more strongly related to
      subsequent or prior glycemic control in type 2 diabetes and to test whether
      patient characteristics modify these longitudinal associations. RESEARCH DESIGN
      AND METHODS: On two occasions separated by 6 months, depressive symptoms and
      glycemic control were assessed in 253 adults with type 2 diabetes. Regression
      analyses examined depressive symptoms as both a predictor and outcome of glycemic
      control and tested whether medication regimen (e.g., insulin versus oral drugs)
      was an effect modifier before and after adjusting for baseline levels of the
      outcome being predicted. RESULTS: Depressive symptom severity predicted poor
      glycemic control 6 months later (P = 0.018) but not after baseline glycemic
      control was taken into account (P = 0.361). Although baseline glycemic control
      did not generally predict depressive symptoms 6 months later (P = 0.558), it
      significantly interacted with regimen (P = 0.008). Specifically, glycemic control
      predicted depressive symptoms among patients prescribed insulin (beta = 0.31, P =
      0.002) but not among those prescribed oral medication alone (beta = -0.10, P =
      0.210). Classifying depression dichotomously produced similar but weaker
      findings. CONCLUSIONS: Depressive symptoms do not necessarily lead to worsened
      glycemic control. In contrast, insulin-treated patients in poor glycemic control
      are at moderate risk for worsening of depressive symptoms. These patients should
      be carefully monitored to determine whether depression treatment should be
      initiated or intensified.

PMID- 19389815
TI  - Association of smoking status, weight change, and incident metabolic syndrome in
      men: a 3-year follow-up study.
AB  - OBJECTIVE: We investigated the incidence of the metabolic syndrome and assessed
      the effect of smoking status and weight change on incident metabolic syndrome.
      RESEARCH DESIGN AND METHODS: This study included 4,542 men without metabolic
      syndrome at baseline who were followed for an average of 3 years. Subjects were
      divided into four categories according to smoking status at baseline and at the 3
      year follow-up. RESULTS: The overall incidence of metabolic syndrome was 10.6%:
      8.0% in nonsmokers, 7.1% in new smokers, 17.1% in ex-smokers, and 13.9% in
      sustained smokers (P < 0.001). In a multivariate regression model, ex-smokers had
      significantly increased odds for incident metabolic syndrome with a mean 1.45
      (95% CI 1.06-1.98) compared with sustained smokers. This was no longer
      significant after including weight change. CONCLUSIONS: Smoking cessation within
      3 years may be a higher risk factor for incident metabolic syndrome than
      sustained smoking, indicating that weight control in ex-smokers is critical to
      attenuate the additional risk for incident metabolic syndrome.

PMID- 19389816
TI  - Reference values for continuous glucose monitoring in Chinese subjects.
AB  - OBJECTIVE: The widespread clinical application of continuous glucose monitoring
      (CGM) is limited by the lack of generally accepted reference values. This
      multicenter study aims to establish preliminary normal reference values for CGM
      parameters in a sample of healthy Chinese subjects. RESEARCH DESIGN AND METHODS:
      A total of 434 healthy individuals with normal glucose regulation completed a 3
      day period of glucose monitoring using a CGM system. The 24-h mean blood glucose
      (24-h MBG) and the percentage of time that subjects' blood glucose levels were
      >or=140 mg/dl (PT140) and <or=70 mg/dl (PT70) within 24 h were analyzed. RESULTS:
      There was excellent compliance of finger stick blood glucose values with CGM
      measurements for subjects. Among the 434 subjects, the daily blood glucose varied
      from 76.9 +/- 11.3 to 144.2 +/- 23.2 mg/dl. The 24-h MBG, PT140, and PT70 were
      104 +/- 10 mg/dl, 4.1 +/- 5.8%, and 2.4 +/- 5.3%, respectively. As for these
      parameters, no significant differences were found between men and women. The 95th
      percentile values were adopted as the upper limits of CGM parameters, which
      revealed 119 mg/dl (6.6 mmol/l) for 24-h MBG, 17.1% for PT140, and 11.7% for
      PT70. CONCLUSIONS: We recommend a 24-h MBG value <119 mg/dl, PT140 <17% (4 h),
      and PT70 <12% (3 h) as normal ranges for the Chinese population.

PMID- 19389817
TI  - Hypoglycemia unawareness is associated with reduced adherence to therapeutic
      decisions in patients with type 1 diabetes: evidence from a clinical audit.
AB  - OBJECTIVE: Hypoglycemia unawareness increases severe hypoglycemia risk.
      Hypoglycemia avoidance restores awareness, but it is difficult to sustain. We
      compared adherence to treatment changes by awareness status. RESEARCH DESIGN AND
      METHODS: Case notes of 90 type 1 diabetic patients were analyzed retrospectively,
      identifying awareness status and insulin regimens over four visits. The
      proportion of patients adhering to advice and percent advice taken were
      calculated. RESULTS: A total of 31 patients with hypoglycemia awareness and 19
      patients with hypoglycemia unawareness were identified, with insulin regimens
      available in 23 and 13, respectively. Patients with hypoglycemia unawareness were
      older (P = 0.001) and had longer diabetes duration (P = 0.002) and lower A1C (P =
      0.007). More patients with hypoglycemia unawareness reported severe hypoglycemia
      (P = 0.002) and fewer were adherent (53.8 vs. 87.0%, P = 0.046), with lower
      adherence scores (42.5 +/- 24.7 vs. 75.3 +/- 27.5%, P = 0.001). CONCLUSIONS:
      Reduced adherence to changes in insulin regimen in hypoglycemia unawareness is
      compatible with habituation to hypoglycemic stress. Therapies aimed at reversing
      repetitive harmful behaviors may be useful to restore hypoglycemia awareness and
      protection from severe hypoglycemia.

PMID- 19389818
TI  - TRIB3 functional Q84R polymorphism is a risk factor for metabolic syndrome and
      carotid atherosclerosis.
AB  - OBJECTIVE: To determine the association of TRIB3 Q84R polymorphism with metabolic
      syndrome (MetS) and carotid atherosclerosis. RESEARCH DESIGN AND METHODS: A case
      control study enrolled 513 Chinese subjects in three groups: control, MetS, and
      obese. The functional TRIB3 Q84R polymorphism was genotyped among subjects
      undergoing carotid ultrasonography. The clinical and biochemical characteristics
      were determined. RESULTS: For individuals with the TRIB3 R84 allele, the odds
      ratio for developing MetS was 2.349 (P = 0.018), abdominal obesity 2.351 (P =
      0.012), hypertriglyceridemia 2.314 (P = 0.00003), and insulin resistance 1.697 (P
      = 0.023). Likewise, the odds ratio for individuals with the TRIB3 R84 allele to
      develop thickened intima-media thickness was 2.208 (P = 0.040). CONCLUSIONS:
      Individuals with the functional TRIB3 Q84R polymorphism are at risk for MetS. The
      TRIB3 R84 allele especially predisposes to carotid atherosclerosis in part
      through the effects of abdominal obesity, hypertriglyceridemia, and insulin
      resistance.

PMID- 19389819
TI  - Abdominal visceral adiposity in the first trimester predicts glucose intolerance
      in later pregnancy.
AB  - OBJECTIVE: To assess whether abdominal adiposity in early pregnancy is associated
      with a higher risk of glucose intolerance at a later gestational stage. RESEARCH
      DESIGN AND METHODS: Subcutaneous and visceral fat was measured with
      ultrasonography at approximately 12 weeks' gestation. A 50-g glucose challenge
      test (GCT) was performed between 24 and 28 weeks' gestation. The risk of having a
      positive GCT (>or=7.8 mmol/l) was determined in association with subcutaneous and
      visceral adipose tissue depths above their respective upper-quartile values
      relative to their bottom three quartile values. RESULTS: Sixty-two women
      underwent GCTs. A visceral adipose tissue depth above the upper quartile value
      was significantly associated with a positive GCT in later pregnancy (adjusted
      odds ratio 16.9 [95% CI 1.5-194.6]). No associations were seen for subcutaneous
      adipose tissue. CONCLUSIONS: Measurement of visceral adipose tissue depth in
      early pregnancy may be associated with glucose intolerance later in pregnancy.

PMID- 19389820
TI  - Comparison of a multiple daily insulin injection regimen (basal once-daily
      glargine plus mealtime lispro) and continuous subcutaneous insulin infusion
      (lispro) in type 1 diabetes: a randomized open parallel multicenter study.
AB  - OBJECTIVE: Insulin pump therapy (continuous subcutaneous insulin infusion [CSII])
      and multiple daily injections (MDIs) with insulin glargine as basal insulin and
      mealtime insulin lispro have not been prospectively compared in people naive to
      either regimen in a multicenter study. We aimed to help close that deficiency.
      RESEARCH DESIGN AND METHODS: People with type 1 diabetes on NPH-based insulin
      therapy were randomized to CSII or glargine-based MDI (both otherwise using
      lispro) and followed for 24 weeks in an equivalence design. Fifty people were
      correctly randomized, and 43 completed the study. RESULTS: Total insulin
      requirement (mean +/- SD) at end point was 36.2 +/- 11.5 units/day on CSII and
      42.6 +/- 15.5 units/day on MDI. Mean A1C fell similarly in the two groups (CSII 
      0.7 +/- 0.7%; MDI -0.6 +/- 0.8%) with a baseline-adjusted difference of -0.1%
      (95% CI -0.5 to 0.3). Similarly, fasting blood glucose and other preprandial,
      postprandial, and nighttime self-monitored plasma glucose levels did not differ
      between the regimens, nor did measures of plasma glucose variability. On CSII,
      1,152 hypoglycemia events were recorded by 23 of 28 participants (82%) and 1,022
      in the MDI group by 27 of 29 patients (93%) (all hypoglycemia differences were
      nonsignificant). Treatment satisfaction score increased more with CSII; however,
      the change in score was similar for the groups. Costs were approximately 3.9
      times higher for CSII. CONCLUSIONS: In unselected people with type 1 diabetes
      naive to CSII or insulin glargine, glycemic control is no better with the more
      expensive CSII therapy compared with glargine-based MDI therapy.

PMID- 19389821
TI  - Oxidative stress and insulin resistance: the coronary artery risk development in
      young adults study.
AB  - OBJECTIVE: Although cumulative evidence suggests that increased oxidative stress
      may lead to insulin resistance in vivo or in vitro, community-based studies are
      scarce. This study examined the longitudinal relationships of oxidative stress
      biomarkers with the development of insulin resistance and whether these
      relationships were independent of obesity in nondiabetic young adults. RESEARCH
      DESIGN AND METHODS: Biomarkers of oxidative stress (F(2)-isoprostanes [F(2)Isop]
      and oxidized LDL [oxLDL]), insulin resistance (the homeostasis model assessment
      of insulin resistance [HOMA-IR]), and various fatness measures (BMI, waist
      circumference, and estimated percent fat) were obtained in a population-based
      observational study (Coronary Artery Risk Development in Young Adults) and its
      ancillary study (Young Adult Longitudinal Trends in Antioxidants) during 2000
      2006. RESULTS: There were substantial increases in estimated mean HOMA-IR over
      time. OxLDL and F(2)Isop showed little association with each other. Mean evolving
      HOMA-IR increased with increasing levels of oxidative stress markers (P < 0.001
      for oxLDL and P = 0.06 for F(2)Isop), measured in 2000-2001. After additional
      adjustment for adiposity, a positive association between oxLDL and HOMA-IR was
      strongly evident, whereas the association between F(2)Isop and HOMA-IR was not.
      CONCLUSIONS: We observed positive associations between each of two oxidative
      stress markers and insulin resistance. The association with oxidized LDL was
      independent of obesity, but that with F(2)Isop was not.

PMID- 19389822
TI  - MALDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers
      and establishment of boosting decision tree model for diagnosis of systemic lupus
      erythematosus.
AB  - OBJECTIVES: To discover novel potential biomarkers and establish a diagnostic
      pattern for SLE by using proteomic technology. METHODS: Serum proteomic spectra
      were generated by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) combined with weak cationic exchange magnetic beads.
      A training set of spectra, derived from analysing sera from 32 patients with SLE,
      43 patients with other autoimmune diseases and 43 age- and sex-matched healthy
      volunteers, was used to train and develop a decision tree model with a machine
      learning algorithm called decision boosting. A blinded testing set, including 32
      patients with SLE, 42 patients with other autoimmune diseases and 40 healthy
      people, was used to determine the accuracy of the model. RESULTS: The diagnostic
      pattern with a panel of four potential protein biomarkers of mass-to-charge (m/z)
      ratio 4070.09, 7770.45, 28 045.1 and 3376.02 could accurately recognize 25 of 32
      patients with SLE, 36 of 42 patients with other autoimmune diseases and 36 of 40
      healthy people. CONCLUSIONS: The preliminary data suggested a potential
      application of MALDI-TOF MS combined with magnetic beads as an effective
      technology to profile serum proteome, and with pattern analysis, a diagnostic
      model comprising four potential biomarkers was indicated to differentiate
      individuals with SLE from RA, SS, SSc and healthy controls rapidly and precisely.

PMID- 19389823
TI  - Lack of bystander activation shows that localization exterior to chromosome
      territories is not sufficient to up-regulate gene expression.
AB  - Position within chromosome territories and localization at transcription
      factories are two facets of nuclear organization that have been associated with
      active gene expression. However, there is still debate about whether this
      organization is a cause or consequence of transcription. Here we induced looping
      out from chromosome territories (CTs), by the activation of Hox loci during
      differentiation, to investigate consequences on neighboring loci. We show that,
      even though flanking genes are caught up in the wave of nuclear reorganization,
      there is no effect on their expression. However, there is a differential
      organization of active and inactive alleles of these genes. Inactive alleles are
      preferentially retained within the CT, whereas actively transcribing alleles, and
      those associated with transcription factories, are found both inside and outside
      of the territory. We suggest that the alleles relocated further to the exterior
      of the CT are those that were already active and already associated with
      transcription factories before the induction of differentiation. Hence active
      gene regions may loop out from CTs because they are able to, and not because they
      need to in order to facilitate gene expression.

PMID- 19389824
TI  - Asymmetric dimethylarginine and mortality in stages 3 to 4 chronic kidney
      disease.
AB  - BACKGROUND AND OBJECTIVES: Asymmetric dimethylarginine (ADMA), an endogenous
      inhibitor of nitric oxide synthase, reduces bioavailability of nitric oxide and
      induces endothelial dysfunction. This dimethylated amino acid accumulates in
      chronic kidney disease and may be involved in the pathophysiology of
      cardiovascular disease (CVD) in this population. DESIGN, SETTINGS, PARTICIPANTS,
      & METHODS: The Modification of Diet in Renal Disease Study was a randomized,
      controlled trial conducted between 1989 and 1993. We measured ADMA in frozen
      samples collected at baseline (n = 820) and obtained survival status, up to
      December 31, 2000, from the National Death Index. We examined the relationship of
      ADMA with prevalent CVD and performed multivariable Cox models to examine the
      relationship of ADMA with all-cause and CVD mortality. RESULTS: Mean (SD) age was
      52 (12) yr, GFR was 32 +/- 12 ml/min per 1.73 m(2), and ADMA was 0.70 +/- 0.25
      micromol/L. A 1-SD increase in ADMA was associated with a 31% increased odds of
      prevalent CVD in an adjusted logistic regression model. During the 10-yr follow
      up period, 202 (25%) participants died of any cause, 122 (15%) from CVD, and 545
      (66%) reached kidney failure. In multivariable Cox models, a 1-SD increase in
      ADMA was associated with a 9% increased risk for all-cause and 19% increased risk
      for CVD mortality. CONCLUSIONS: In this cohort of patients with predominantly
      nondiabetic, stages 3 to 4 chronic kidney disease, there was a strong association
      of ADMA with prevalent CVD and a modest association with all-cause and CVD
      mortality.

PMID- 19389825
TI  - Patient dialysis knowledge is associated with permanent arteriovenous access use
      in chronic hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Patient knowledge about chronic hemodialysis (CHD) is
      important for effective self-management behaviors, but little is known about its
      association with vascular access use. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Prospective cohort of adult incident CHD patients from May 2002
      until November 2005 and followed for 6 mo after initiation of hemodialysis (HD).
      Patient knowledge was measured using the Chronic Hemodialysis Knowledge Survey
      (CHeKS). The primary outcome was dialysis access type at: baseline, 3 mo, and 6
      mo after HD initiation. Secondary outcomes included anemia, nutritional, and
      mineral laboratory measures. RESULTS: In 490 patients, the median (interquartile
      range) CHeKS score (0 to 100%) was 65%[52% to 78%]. Lower scores were associated
      with older age, fewer years of education, and nonwhite race. Patients with CHeKS
      scores 20 percentage points higher were more likely to use an arteriovenous
      fistula or graft compared with a catheter at HD initiation and 6 mo after
      adjustment for age, sex, race, education, and diabetes mellitus. No statistically
      significant associations were found between knowledge and laboratory outcome
      measures, except for a moderate association with serum albumin. Potential
      limitations include residual confounding and an underpowered study to determine
      associations with some clinical measures. CONCLUSIONS: Patients with less
      dialysis knowledge may be less likely to use an arteriovenous access for dialysis
      at initiation and after starting hemodialysis. Additional studies are needed to
      explore the impact of patient dialysis knowledge, and its improvement after
      educational interventions, on vascular access in hemodialysis.

PMID- 19389826
TI  - Linkage disequilibrium mapping of the replicated type 2 diabetes linkage signal
      on chromosome 1q.
AB  - OBJECTIVE: Linkage of the chromosome 1q21-25 region to type 2 diabetes has been
      demonstrated in multiple ethnic groups. We performed common variant fine-mapping
      across a 23-Mb interval in a multiethnic sample to search for variants
      responsible for this linkage signal. RESEARCH DESIGN AND METHODS: In all, 5,290
      single nucleotide polymorphisms (SNPs) were successfully genotyped in 3,179 type
      2 diabetes case and control subjects from eight populations with evidence of 1q
      linkage. Samples were ascertained using strategies designed to enhance power to
      detect variants causal for 1q linkage. After imputation, we estimate
      approximately 80% coverage of common variation across the region (r (2) > 0.8,
      Europeans). Association signals of interest were evaluated through in silico
      replication and de novo genotyping in approximately 8,500 case subjects and
      12,400 control subjects. RESULTS: Association mapping of the 23-Mb region
      identified two strong signals, both of which were restricted to the subset of
      European-descent samples. The first mapped to the NOS1AP (CAPON) gene region
      (lead SNP: rs7538490, odds ratio 1.38 [95% CI 1.21-1.57], P = 1.4 x 10(-6), in
      999 case subjects and 1,190 control subjects); the second mapped within an
      extensive region of linkage disequilibrium that includes the ASH1L and PKLR genes
      (lead SNP: rs11264371, odds ratio 1.48 [1.18-1.76], P = 1.0 x 10(-5), under a
      dominant model). However, there was no evidence for association at either signal
      on replication, and, across all data (>24,000 subjects), there was no indication
      that these variants were causally related to type 2 diabetes status. CONCLUSIONS:
      Detailed fine-mapping of the 23-Mb region of replicated linkage has failed to
      identify common variant signals contributing to the observed signal. Future
      studies should focus on identification of causal alleles of lower frequency and
      higher penetrance.

PMID- 19389827
TI  - Hypothalamic reactive oxygen species are required for insulin-induced food intake
      inhibition: an NADPH oxidase-dependent mechanism.
AB  - OBJECTIVE: Insulin plays an important role in the hypothalamic control of energy
      balance, especially by reducing food intake. Emerging data point to a pivotal
      role of reactive oxygen species (ROS) in energy homeostasis regulation, but their
      involvement in the anorexigenic effect of insulin is unknown. Furthermore, ROS
      signal derived from NADPH oxidase activation is required for physiological
      insulin effects in peripheral cells. In this study, we investigated the
      involvement of hypothalamic ROS and NADPH oxidase in the feeding behavior
      regulation by insulin. RESEARCH DESIGN AND METHODS: We first measured
      hypothalamic ROS levels and food intake after acute intracerebroventricular
      injection of insulin. Second, effect of pretreatment with a ROS scavenger or an
      NADPH oxidase inhibitor was evaluated. Third, we examined the consequences of two
      nutritional conditions of central insulin unresponsiveness (fasting or short-term
      high-fat diet) on the ability of insulin to modify ROS level and food intake.
      RESULTS: In normal chow-fed mice, insulin inhibited food intake. At the same
      dose, insulin rapidly and transiently increased hypothalamic ROS levels by 36%.
      The pharmacological suppression of this insulin-stimulated ROS elevation, either
      by antioxidant or by an NADPH oxidase inhibitor, abolished the anorexigenic
      effect of insulin. Finally, in fasted and short-term high-fat diet-fed mice,
      insulin did not promote elevation of ROS level and food intake inhibition, likely
      because of an increase in hypothalamic diet-induced antioxidant defense systems.
      CONCLUSIONS: A hypothalamic ROS increase through NADPH oxidase is required for
      the anorexigenic effect of insulin.

PMID- 19389828
TI  - (Pro)renin receptor-mediated signal transduction and tissue renin-angiotensin
      system contribute to diabetes-induced retinal inflammation.
AB  - OBJECTIVE: The term "receptor-associated prorenin system" (RAPS) refers to the
      pathogenic mechanisms whereby prorenin binding to its receptor dually activates
      the tissue renin-angiotensin system (RAS) and RAS-independent intracellular
      signaling via the receptor. The aim of the present study was to define the
      association of the RAPS with diabetes-induced retinal inflammation. RESEARCH
      DESIGN AND METHODS: Long-Evans rats, C57BL/6 mice, and angiotensin II type 1
      receptor (AT1-R)-deficient mice with streptozotocin-induced diabetes were treated
      with (pro)renin receptor blocker (PRRB). Retinal mRNA expression of prorenin and
      the (pro)renin receptor was examined by quantitative RT-PCR. Leukocyte adhesion
      to the retinal vasculature was evaluated with a concanavalin A lectin perfusion
      labeling technique. Retinal protein levels of vascular endothelial growth factor
      (VEGF) and intercellular adhesion molecule (ICAM)-1 were examined by ELISA.
      Retinal extracellular signal-regulated kinase (ERK) activation was analyzed by
      Western blotting. RESULTS: Induction of diabetes led to significant increase in
      retinal expression of prorenin but not the (pro)renin receptor. Retinal adherent
      leukocytes were significantly suppressed with PRRB. Administration of PRRB
      inhibited diabetes-induced retinal expression of VEGF and ICAM-1. To clarify the
      role of signal transduction via the (pro)renin receptor in the diabetic retina,
      we used AT1-R-deficient mice in which the RAS was deactivated. Retinal adherent
      leukocytes in AT1-R-deficient diabetic mice were significantly suppressed with
      PRRB. PRRB suppressed the activation of ERK and the production of VEGF, but not
      ICAM-1, in AT1-R-deficient diabetic mice. CONCLUSIONS: These results indicate a
      significant contribution of the RAPS to the pathogenesis of diabetes-induced
      retinal inflammation, suggesting the possibility of the (pro)renin receptor as a
      novel molecular target for the treatment of diabetic retinopathy.

PMID- 19389829
TI  - The progesterone receptor coactivator Hic-5 is involved in the pathophysiology of
      endometriosis.
AB  - Endometriosis is an estrogen-dependent disorder primarily associated with pelvic
      pain and infertility in up to 10% of women of reproductive age. Recent studies
      suggest that resistance to progesterone action may contribute to the development
      and pathophysiology of this disorder. In this study we examined the in vivo and
      in vitro expression and function of one progesterone receptor (PR) coactivator,
      Hic-5, in human endometrium and endometrial stromal fibroblasts (hESFs) from 29
      women with and 30 (control) women without endometriosis. Hic-5 was highly
      expressed in stromal, but not epithelial, cells in women without endometriosis,
      in a cycle-dependent manner. In contrast, Hic-5 expression was not regulated
      during the menstrual cycle in hESFs from women with endometriosis and was
      significantly reduced in hESFs from women with vs. without disease. Hic-5 mRNA
      expression throughout the cycle in endometrium from control women, but not those
      with endometriosis, correlated with expression of PR. Hic-5 mRNA in hESFs was
      significantly up-regulated in control but not endometriosis hESFs after treatment
      in vitro with 8-bromoadenosine-cAMP for 96 h but only modestly after 14 d of
      progesterone treatment. Hic-5 silencing did not influence cAMP-regulated gene
      expression but affected genes regulated solely by progesterone (e.g. DKK1 and
      calcitonin). Together the data suggest that the proposed progesterone resistance
      in endometrium from women with endometriosis derives, in part, from impaired
      expression of the PR coactivator, Hic-5, in endometrial tissue and cultured
      endometrial stromal fibroblasts.

PMID- 19389830
TI  - Minireview: finding the sweet spot: peripheral versus central glucagon-like
      peptide 1 action in feeding and glucose homeostasis.
AB  - Glucagon-like peptide 1 (GLP-1) is both a gut-derived hormone and a
      neurotransmitter synthesized in the brain. Early reports suggested that GLP-1
      acts in the periphery to promote insulin secretion and affect glucose
      homeostasis, whereas central GLP-1 reduces food intake and body weight. However,
      current research indicates that in fact, GLP-1 in each location plays a role in
      these functions. This review summarizes the evidence for involvement of
      peripheral and brain GLP-1 in food intake regulation and glucose homeostasis and
      proposes a model for the coordinated actions of GLP-1 at multiple sites.

PMID- 19389831
TI  - Attenuation of induced hyperthyroidism in mice by pretreatment with thyrotropin
      receptor protein: deviation of thyroid-stimulating to nonfunctional antibodies.
AB  - Graves'-like hyperthyroidism is induced by immunizing BALB/c mice with adenovirus
      expressing the thyrotropin receptor (TSHR) or its A-subunit. Nonantigen-specific
      immune strategies can block disease development and some reduce established
      hyperthyroidism, but these approaches may have unforeseen side effects. Without
      immune stimulation, antigens targeted to the mannose receptor induce tolerance.
      TSHR A-subunit protein generated in eukaryotic cells binds to the mannose
      receptor. We tested the hypothesis that eukaryotic A-subunit injected into BALB/c
      mice without immune stimulation would generate tolerance and protect against
      hyperthyroidism induced by subsequent immunization with A-subunit adenovirus.
      Indeed, one sc injection of eukaryotic, glycosylated A-subunit protein 1 wk
      before im A-subunit-adenovirus immunization reduced serum T(4) levels and the
      proportion of thyrotoxic mice decreased from 77 to 22%. Prokaryotic A-subunit and
      other thyroid proteins (thyroglobulin and thyroid peroxidase) were ineffective. A
      subunit pretreatment reduced thyroid-stimulating and TSH-binding inhibiting
      antibodies, but, surprisingly, TSHR-ELISA antibodies were increased. Rather than
      inducing tolerance, A-subunit pretreatment likely expanded B cells that secrete
      nonfunctional antibodies. Follow-up studies supported this possibility and also
      showed that eukaryotic A-subunit administration could not reverse hyperthyroidism
      in mice with established disease. In conclusion, glycosylated TSHR A-subunit is a
      valuable immune modulator when used before immunization. It acts by deviating
      responses away from pathogenic toward nonfunctional antibodies, thereby
      attenuating induction of hyperthyroidism. However, this protein treatment does
      not reverse established hyperthyroidism. Our findings suggest that prophylactic
      TSHR A-subunit protein administration in genetically susceptible individuals may
      deviate the autoantibody response away from pathogenic epitopes and provide
      protection against future development of Graves' disease.

PMID- 19389832
TI  - Activin signaling: effects on body composition and mitochondrial energy
      metabolism.
AB  - Activin-betaA and activin-betaB (encoded by Inhba and Inhbb genes, respectively)
      are closely related TGF-beta superfamily members that participate in a variety of
      biological processes. We previously generated mice with an insertion allele at
      the Inhba locus, Inhba(BK). In this allele, the sequence encoding the Inhba
      mature domain is replaced with that of Inhbb, rendering the gene product
      functionally hypomorphic. Homozygous (Inhba(BK/BK)) and hemizygous (Inhba(BK/-))
      mice are smaller and leaner than their wild-type littermates, and many tissues
      are disproportionately small relative to total body weight. To determine the
      mechanisms that contribute to these phenomena, we investigated the metabolic
      consequences of the mutation. Although the growth of Inhba(BK) mice is improved
      by providing a calorie-rich diet, diet-induced obesity, fatty liver, and insulin
      resistance (hallmarks of chronic caloric excess) do not develop, despite greater
      caloric intake than wild-type controls. Physiological, molecular, and biochemical
      analyses all revealed characteristics that are commonly associated with increased
      mitochondrial energy metabolism, with a corresponding up-regulation of several
      genes that reflect enhanced mitochondrial biogenesis and function. Oxygen
      consumption, an indirect measure of the metabolic rate, was markedly increased in
      Inhba(BK/BK) mice, and polarographic analysis of liver mitochondria revealed an
      increase in ADP-independent oxygen consumption, consistent with constitutive
      uncoupling of the inner mitochondrial membrane. These findings establish a
      functional relationship between activin signaling and mitochondrial energy
      metabolism and further support the rationale to target this signaling pathway for
      the medical treatment of cachexia, obesity, and diabetes.

PMID- 19389833
TI  - Pioglitazone inhibits Toll-like receptor expression and activity in human
      monocytes and db/db mice.
AB  - Toll-like receptors (TLRs) are key innate immune sensors of endogenous damage
      signals and play an important role in inflammatory diseases like diabetes and
      atherosclerosis. Pioglitazone (PIO), a peroxisome proliferator-activated receptor
      (PPAR)-gamma agonist, has been reported to be an antiinflammatory agent. Thus, in
      the present study, we examined the antiinflammatory effects of PIO on TLR2 and
      TLR4 expression in human monocytes exposed to Pam3CSK4 (Pam; TLR2 ligand) and
      purified lipopolysaccharide (LPS; TLR4 ligand) using flow cytometry and real-time
      RT-PCR. Monocytes were isolated from healthy human volunteers and pretreated with
      PIO (1 microM) followed by Pam (170 ng/ml) and LPS (160 ng/ml) challenge. PIO
      significantly decreased Pam- and LPS-induced TLR2 (-56%) and TLR4 (-78%)
      expression (P < 0.05). In addition, PIO decreased TLR ligand-induced nuclear
      factor-kappaB activity (-63%), IL-1beta (-50%), IL-6 (-52%), monocyte
      chemoattractant protein-1(-83%), and TNF-alpha (-87%) compared with control.
      Next, PIO-treated db/db mice (n = 6/group) showed decreased TLR2 (-60%) and TLR4
      (-45%) expression in peritoneal macrophages compared with vehicle control mice (P
      < 0.001) with associated decrease in MyD88-dependent signaling and nuclear factor
      kappaB activation. Data suggest that Pam- and LPS-induced TLR2 and TLR4
      expression are inhibited by PIO in human monocytes and db/db mice. Thus, we
      define a novel pathway by which PIO could induce antiinflammatory effects.

PMID- 19389834
TI  - Hypothyroidism decreases the biogenesis in free mitochondria and neuronal oxygen
      consumption in the cerebral cortex of developing rats.
AB  - Thyroid hormone plays a critical role in mitochondrial biogenesis in two areas of
      the developing brain, the cerebral cortex and the striatum. Here we analyzed, in
      the cerebral cortex of neonatal rats, the effect of hypothyroidism on the
      biogenesis in free and synaptosomal mitochondria by analyzing, in isolated
      mitochondria, the activity of respiratory complex I, oxidative phosphorylation,
      oxygen consumption, and the expression of mitochondrial genome. In addition, we
      studied the effect of thyroid hormone in oxygen consumption in vivo by
      determining metabolic flow through (13)C nuclear magnetic resonance spectroscopy.
      Our results clearly show that in vivo, hypothyroidism markedly reduces oxygen
      consumption in the neural population of the cerebral cortex. This effect
      correlates with decreased free mitochondria biogenesis. In contrast, no effect
      was observed in the biogenesis in synaptosomal mitochondria. The parameters
      analyzed were markedly improved after T(3) administration. These results suggest
      that a reduced biogenesis and the subsequent reduction of respiratory capacity in
      free mitochondria could be the underlying cause of decreased oxygen consumption
      in the neurons of the cerebral cortex of hypothyroid neonates.

PMID- 19389835
TI  - In vivo and ex vivo regulation of visfatin production by leptin in human and
      murine adipose tissue: role of mitogen-activated protein kinase and
      phosphatidylinositol 3-kinase signaling pathways.
AB  - Visfatin is an adipogenic adipokine with increased levels in obesity, properties
      common to leptin. Thus, leptin may modulate visfatin production in adipose tissue
      (AT). Therefore, we investigated the effects of leptin on visfatin levels in 3T3
      L1 adipocytes and human/murine AT, with or without a leptin antagonist. The
      potential signaling pathways and mechanisms regulating visfatin production in AT
      was also studied. Real-time RT-PCR and Western blotting were used to assess the
      relative mRNA and protein expression of visfatin. ELISA was performed to measure
      visfatin levels in conditioned media of AT explants, and small interfering RNA
      technology was used to reduce leptin receptor expression. Leptin significantly (P
      < 0.01) increased visfatin levels in human and murine AT with a maximal response
      at leptin 10(-9) M, returning to baseline at leptin 10(-7) M. Importantly, ip
      leptin administration to C57BL/6 ob/ob mice further supported leptin-induced
      visfatin protein production in omental AT (P < 0.05). Additionally, soluble
      leptin receptor levels rose with concentration dependency to a maximal response
      at leptin 10(-7) M (P < 0.01). The use of a leptin antagonist negated the
      induction of visfatin and soluble leptin receptor by leptin. Furthermore, leptin
      induced visfatin production was significantly decreased in the presence of MAPK
      and phosphatidylinositol 3-kinase inhibitors. Also, when the leptin receptor gene
      was knocked down using small interfering RNA, leptin-induced visfatin expression
      was significantly decreased. Thus, leptin increases visfatin production in AT in
      vivo and ex vivo via pathways involving MAPK and phosphatidylinositol 3-kinase
      signaling. The pleiotropic effects of leptin may be partially mediated by
      visfatin.

PMID- 19389836
TI  - Estradiol increases guanosine 5'-triphosphate cyclohydrolase expression via the
      nitric oxide-mediated activation of cyclic adenosine 5'-monophosphate response
      element binding protein.
AB  - A number of studies have demonstrated that estradiol can stimulate endothelial
      nitric oxide synthase expression and activity, resulting in enhanced nitric oxide
      (NO) generation. However, its effect on the NO synthase cofactor,
      tetrahydrobiopterin are less clear. Cellular tetrahydrobiopterin levels are
      regulated, at least in part, by GTP cyclohydrolase 1 (GCH1). Thus, the purpose of
      this study was to determine the effect of estradiol on GCH1 expression and the
      regulatory mechanisms in pulmonary arterial endothelial cells. Our data indicate
      that 17beta-estradiol (E2) increases GCH1 transcription in a dose- and time
      dependent manner, whereas estrogen receptor antagonism or NO synthase inhibition
      attenuated E2-stimulated GCH1 expression. Analysis of the GCH1 promoter fragment
      responsive to E2 revealed the presence of a cAMP response element, and we found
      that E2 triggers a rapid but transient elevation of phospho-cAMP response element
      binding protein (CREB; <1 h) followed by a second sustained rise after 6 h. EMSA
      analysis revealed an increase in the binding of CREB during E2 treatment and
      mutation of the cAMP response element in the GCH1 promoter attenuated the E2
      mediated increase in transcription. Furthermore, inhibition of the cAMP-dependent
      kinase, protein kinase A (PKA) completely abolished the E2-stimulated GCH1
      promoter activity, whereas the stimulation of cAMP levels with forskolin
      increased GCH1 promoter activity, indicating the key role of cAMP in regulating
      GCH1 promoter activity. In conclusion, our results demonstrate that estradiol can
      modulate GCH1 expression via NO-mediated activation of CREB in pulmonary arterial
      endothelial cells. These findings provide new insight into the vascular
      protective effect of estradiol.

PMID- 19389838
TI  - Sexual history disclosure polygraph examinations with cybercrime offences: a
      first Dutch explorative study.
AB  - This article presents the first study on post-conviction polygraphy in the
      Netherlands. Importantly, it exclusively focuses on cybercrime offenders. The
      study is designed to systematically address the different child sexual behaviours
      exhibited by 25 participants who are in treatment for possessing child abuse
      images. The results indicate that post-conviction polygraphy can provide
      additional data to inform the development of theory in this area and contribute
      to the treatment, supervision, and more effective containment of offending
      behaviour and the reduction of future victimization.

PMID- 19389837
TI  - Regulation and function of tissue inhibitor of metalloproteinase (TIMP) 1 and
      TIMP3 in periovulatory rat granulosa cells.
AB  - In the ovary, the matrix metalloproteinases (MMPs) and the tissue inhibitors of
      metalloproteinase (TIMPs) have been postulated to regulate extracellular matrix
      remodeling associated with ovulation. In the present study, we investigated the
      regulatory mechanisms controlling expression of Timp1 and Timp3 mRNA in
      periovulatory granulosa cells. Granulosa cells were isolated from immature
      pregnant mare serum gonadotropin-primed (10 IU) rat ovaries and treated with
      human chorionic gonadotropin (hCG; 1 IU/ml). At 4 h after hCG treatment, Timp1
      expression was highest and then decreased gradually over the remaining 24 h of
      culture. In contrast, hCG induced a biphasic increase of Timp3 expression at 2
      and 16 h. The hCG stimulated expression of Timp1 and Timp3 mRNA was blocked by
      inhibitors of the protein kinase A (H89), protein kinase C (GF109203), and MAPK
      (SB2035850) pathways. To further explore Timp1 and Timp3 regulation, cells were
      cultured with the progesterone receptor antagonist RU486, which blocked the hCG
      induction of Timp3 expression, whereas the epidermal growth factor receptor
      tyrosine kinase inhibitor AG1478 blocked the hCG stimulation of both Timp1 and
      Timp3 expression. The prostaglandin-endoperoxide synthase 2 inhibitor NS-398 had
      no effect. The potential function of TIMP3 was investigated with Timp3-specific
      small interfering RNA treatment. Timp3 small interfering RNA resulted in a 20%
      decrease in hCG-induced progesterone levels and microarray analysis revealed an
      increase in cytochrome P450 Cyp 17, ubiquitin conjugating enzyme E2T, and heat
      shock protein 70. IGF binding protein 5, stearyl-CoA desaturase, and annexin A1
      were decreased. The differential regulation between Timp1 and Timp3 may correlate
      with their unique roles in the processes of ovulation and luteinization. For
      TIMP3, this may include regulating fatty acid synthesis, steroidogenesis, and
      protein turnover.

PMID- 19389839
TI  - Microvesicles from mesenchymal stromal cells protect against acute kidney injury.

PMID- 19389840
TI  - Lessons from geographic variations in predialysis nephrology care.

PMID- 19389841
TI  - CKD classification: time to move beyond KDOQI.

PMID- 19389842
TI  - 17 and 23: prime numbers that matter.

PMID- 19389844
TI  - Plasma gelsolin and circulating actin correlate with hemodialysis mortality.
AB  - Plasma gelsolin (pGSN) binds actin and bioactive mediators to localize
      inflammation. Low pGSN correlates with adverse outcomes in acute injury, whereas
      administration of recombinant pGSN reduces mortality in experimental sepsis. We
      found that mean pGSN levels of 150 patients randomly selected from 10,044
      starting chronic hemodialysis were 140 +/- 42 mg/L, 30 to 50% lower than levels
      reported for healthy individuals. In a larger sample, we performed a case-control
      analysis to evaluate the relationship of pGSN and circulating actin with
      mortality; pGSN levels were significantly lower in 114 patients who died within 1
      yr of dialysis initiation than in 109 survivors (117 +/- 38 mg/L versus 147 +/-
      42 mg/L, P < 0.001). pGSN levels had a graded, inverse relationship with 1-yr
      mortality, such that patients with pGSN < 130 mg/L experienced a > 3-fold risk
      for mortality compared with those with pGSN > or = 150 mg/L. The 69% of patients
      with detectable circulating actin had lower pGSN levels than those without (127
      +/- 45 mg/L versus 141 +/- 36 mg/L, P = 0.026). Compared with patients who had
      elevated pGSN and no detectable actin, those with low pGSN levels and detectable
      actin had markedly increased mortality (odds ratio 9.8, 95% confidence interval
      2.9 to 33.5). Worsening renal function correlated with pGSN decline in 53
      subjects with CKD not on dialysis. In summary, low pGSN and detectable
      circulating actin identify chronic hemodialysis patients at highest risk for 1-yr
      mortality.

PMID- 19389845
TI  - Molecular correlates of renal function in kidney transplant biopsies.
AB  - The molecular changes in the parenchyma that reflect disturbances in the function
      of kidney transplants are unknown. We studied the relationships among
      histopathology, gene expression, and renal function in 146 human kidney
      transplant biopsies performed for clinical indications. Impaired function
      (estimated GFR) correlated with tubular atrophy and fibrosis but not with
      inflammation or rejection. Functional deterioration before biopsy correlated with
      inflammation and tubulitis and was greater in cases of rejection. Microarray
      analysis revealed a correlation between impaired renal function and altered
      expression of sets of transcripts consistent with tissue injury but not with
      those consistent with cytotoxic T cell infiltration or IFN-gamma effects.
      Multivariate analysis of clinical variables, histologic lesions, and transcript
      sets confirmed that expression of injury-related transcript sets independently
      correlated with renal function. Analysis of individual genes confirmed that the
      transcripts with the greatest positive or negative correlations with renal
      function were those suggestive of response to injury and parenchymal
      dedifferentiation not inflammation. We defined new sets of genes based on
      individual transcripts that correlated with renal function, and these highly
      correlated with the previously developed injury sets and with atrophy and
      fibrosis. Thus, in biopsies performed for clinical reasons, functional
      disturbances are reflected in transcriptome changes representing tissue injury
      and dedifferentiation but not the inflammatory burden.

PMID- 19389846
TI  - Possible effects of the new Medicare reimbursement policy on African Americans
      with ESRD.

PMID- 19389847
TI  - Mesenchymal stem cell-derived microvesicles protect against acute tubular injury.
AB  - Administration of mesenchymal stem cells (MSCs) improves the recovery from acute
      kidney injury (AKI). The mechanism may involve paracrine factors promoting
      proliferation of surviving intrinsic epithelial cells, but these factors remain
      unknown. In the current study, we found that microvesicles derived from human
      bone marrow MSCs stimulated proliferation in vitro and conferred resistance of
      tubular epithelial cells to apoptosis. The biologic action of microvesicles
      required their CD44- and beta1-integrin-dependent incorporation into tubular
      cells. In vivo, microvesicles accelerated the morphologic and functional recovery
      of glycerol-induced AKI in SCID mice by inducing proliferation of tubular cells.
      The effect of microvesicles on the recovery of AKI was similar to the effect of
      human MSCs. RNase abolished the aforementioned effects of microvesicles in vitro
      and in vivo, suggesting RNA-dependent biologic effects. Microarray analysis and
      quantitative real time PCR of microvesicle-RNA extracts indicate that
      microvesicles shuttle a specific subset of cellular mRNA, such as mRNAs
      associated with the mesenchymal phenotype and with control of transcription,
      proliferation, and immunoregulation. These results suggest that microvesicles
      derived from MSCs may activate a proliferative program in surviving tubular cells
      after injury via a horizontal transfer of mRNA.

PMID- 19389848
TI  - Activation of the succinate receptor GPR91 in macula densa cells causes renin
      release.
AB  - Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) are salt sensors
      and generate paracrine signals that control renal blood flow, glomerular
      filtration, and release of the prohypertensive hormone renin. We hypothesized
      that the recently identified succinate receptor GPR91 is present in MD cells and
      regulates renin release. Using immunohistochemistry, we identified GPR91 in the
      apical plasma membrane of MD cells. Treatment of MD cells with succinate
      activated mitogen-activated protein kinases (MAPKs; p38 and extracellular signal
      regulated kinases 1/2) and cyclooxygenase 2 (COX-2) and induced the synthesis and
      release of prostaglandin E(2), a potent vasodilator and classic paracrine
      mediator of renin release. Using microperfused JGA and real-time confocal
      fluorescence imaging of quinacrine-labeled renin granules, we detected
      significant renin release in response to tubular succinate (EC(50) 350 microM).
      Genetic deletion of GPR91 (GPR91(-/-) mice) or pharmacologic inhibition of MAPK
      or COX-2 blocked succinate-induced renin release. Streptozotocin-induced diabetes
      caused GPR91-dependent upregulation of renal cortical phospho-p38, extracellular
      signal-regulated kinases 1/2, COX-2, and renin content. Salt depletion for 1 wk
      increased plasma renin activity seven-fold in wild-type mice but only 3.4-fold in
      GPR91(-/-) mice. In summary, MD cells can sense alterations in local tissue
      metabolism via accumulation of tubular succinate and GPR91 signaling, which
      involves the activation of MAPKs, COX-2, and the release of prostaglandin E(2).
      This mechanism may be integral in the regulation of renin release and activation
      of the renin-angiotensin system in health and disease.

PMID- 19389849
TI  - "Nature versus nurture" study of deceased-donor pairs in kidney transplantation.
AB  - Donor characteristics such as age and cause of death influence the incidence of
      delayed graft function (DGF) and graft survival; however, the relative influence
      of donor characteristics ("nature") versus transplant center characteristics
      ("nurture") on deceased-donor kidney transplant outcomes is unknown. We examined
      the risks for DGF and allograft failure within 19,461 recipient pairs of the same
      donor's kidneys using data from the US Renal Data System. For the 11,894 common
      donor pairs transplanted at different centers, a recipient was twice as likely to
      develop DGF when the recipient of the contralateral kidney developed DGF (odds
      ratio [OR] 2.05; 95% confidence interval [CI] 1.82 to 2.30). Similarly, for 7567
      common-donor pairs transplanted at the same center, the OR for DGF was 3.02 (95%
      CI 2.62 to 3.48). For pairs transplanted at the same center, there was an
      additional 42% risk for DGF compared with pairs transplanted at different
      centers. After adjustment for DGF, the within-pair ORs for allograft failure by 1
      yr were 1.92 (95% CI 1.33 to 2.77) and 1.77 (95% CI 1.25 to 2.52) for recipients
      who underwent transplantation at the same center and different centers,
      respectively. These data suggest that both unmeasured donor characteristics and
      transplant center characteristics contribute to the risk for DGF and that the
      former also contribute significantly to allograft failure.

PMID- 19389850
TI  - HNF1B mutations associate with hypomagnesemia and renal magnesium wasting.
AB  - Mutations in hepatocyte nuclear factor 1B (HNF1B), which is a transcription
      factor expressed in tissues including renal epithelia, associate with abnormal
      renal development. While studying renal phenotypes of children with HNF1B
      mutations, we identified a teenager who presented with tetany and hypomagnesemia.
      We retrospectively reviewed radiographic and laboratory data for all patients
      from a single center who had been screened for an HNF1B mutation. We found
      heterozygous mutations in 21 (23%) of 91 cases of renal malformation. All
      mutation carriers had abnormal fetal renal ultrasonography. Plasma magnesium
      levels were available for 66 patients with chronic kidney disease (stages 1 to
      3). Striking, 44% (eight of 18) of mutation carriers had hypomagnesemia (<1.58
      mg/dl) compared with 2% (one of 48) of those without mutations (P < 0.0001). The
      median plasma magnesium was significantly lower among mutation carriers than
      those without mutations (1.68 versus 2.02 mg/dl; P < 0.0001). Because
      hypermagnesuria and hypocalciuria accompanied the hypomagnesemia, we analyzed
      genes associated with hypermagnesuria and detected highly conserved HNF1
      recognition sites in FXYD2, a gene that can cause autosomal dominant
      hypomagnesemia and hypocalciuria when mutated. Using a luciferase reporter assay,
      we demonstrated HNF1B-mediated transactivation of FXYD2. These results extend the
      phenotype of HNF1B mutations to include hypomagnesemia. HNF1B regulates
      transcription of FXYD2, which participates in the tubular handling of Mg(2+),
      thus describing a role for HNF1B not only in nephrogenesis but also in the
      maintenance of tubular function.

PMID- 19389851
TI  - Reduced production of creatinine limits its use as marker of kidney injury in
      sepsis.
AB  - Although diagnosis and staging of acute kidney injury uses serum creatinine,
      acute changes in creatinine lag behind both renal injury and recovery. The risk
      for mortality increases when acute kidney injury accompanies sepsis; therefore,
      we sought to explore the limitations of serum creatinine in this setting. In
      mice, induction of sepsis by cecal ligation and puncture in bilaterally
      nephrectomized mice increased markers of nonrenal organ injury and serum TNF
      alpha. Serum creatinine, however, was significantly lower in septic animals than
      in animals subjected to bilateral nephrectomy and sham cecal ligation and
      puncture. Under these conditions treatment with chloroquine decreased nonrenal
      organ injury markers but paradoxically increased serum creatinine. Sepsis
      dramatically decreased production of creatinine in nephrectomized mice, without
      changes in body weight, hematocrit, or extracellular fluid volume. In conclusion,
      sepsis reduces production of creatinine, which blunts the increase in serum
      creatinine after sepsis, potentially limiting the early detection of acute kidney
      injury. This may partially explain why small absolute increases in serum
      creatinine levels are associated with poor clinical outcomes. These data support
      the need for new biomarkers that provide better measures of renal injury,
      especially in patients with sepsis.

PMID- 19389852
TI  - Fetuin-A protects against atherosclerotic calcification in CKD.
AB  - Reduced serum levels of the calcification inhibitor fetuin-A associate with
      increased cardiovascular mortality in dialysis patients. Fetuin-A-deficient mice
      display calcification of various tissues but notably not of the vasculature. This
      absence of vascular calcification may result from the protection of an intact
      endothelium, which becomes severely compromised in the setting of
      atherosclerosis. To test this hypothesis, we generated fetuin-A/apolipoprotein E
      (ApoE)-deficient mice and compared them with ApoE-deficient and wild-type mice
      with regard to atheroma formation and extraosseous calcification. We assigned
      mice to three treatment groups for 9 wk: (1) Standard diet, (2) high-phosphate
      diet, or (3) unilateral nephrectomy (causing chronic kidney disease [CKD]) plus
      high-phosphate diet. Serum urea, phosphate, and parathyroid hormone levels were
      similar in all genotypes after the interventions. Fetuin-A deficiency did not
      affect the extent of aortic lipid deposition, neointima formation, and coronary
      sclerosis observed with ApoE deficiency, but the combination of fetuin-A
      deficiency, hyperphosphatemia, and CKD led to a 15-fold increase in vascular
      calcification in this model of atherosclerosis. Fetuin-A deficiency almost
      exclusively promoted intimal rather than medial calcification of atheromatous
      lesions. High-phosphate diet and CKD also led to an increase in valvular
      calcification and aorta-associated apoptosis, with wild-type mice having the
      least, ApoE-deficient mice intermediate, and fetuin-A/ApoE-deficient mice the
      most. In addition, the combination of fetuin-A deficiency, high-phosphate diet,
      and CKD in ApoE-deficient mice greatly enhanced myocardial calcification, whereas
      the absence of fetuin-A did not affect the incidence of renal calcification. In
      conclusion, fetuin-A inhibits pathologic calcification in both the soft tissue
      and vasculature, even in the setting of atherosclerosis.

PMID- 19389853
TI  - P2X7 deficiency attenuates renal injury in experimental glomerulonephritis.
AB  - The P2X7 receptor is a ligand-gated cation channel that is normally expressed by
      a variety of immune cells, including macrophages and lymphocytes. Because it
      leads to membrane blebbing, release of IL-1beta, and cell death by apoptosis or
      necrosis, it is a potential therapeutic target for a variety of inflammatory
      diseases. Although the P2X7 receptor is usually not detectable in normal renal
      tissue, we previously reported increased expression of both mRNA and protein in
      mesangial cells and macrophages infiltrating the glomeruli in animal models of
      antibody-mediated glomerulonephritis. In this study, we used P2X7-knockout mice
      in the same experimental model of glomerulonephritis and found that P2X7
      deficiency was significantly renoprotective compared with wild-type controls,
      evidenced by better renal function, a striking reduction in proteinuria, and
      decreased histologic glomerular injury. In addition, the selective P2X7
      antagonist A-438079 prevented the development of antibody-mediated
      glomerulonephritis in rats. These results support a proinflammatory role for P2X7
      in immune-mediated renal injury and suggest that the P2X7 receptor is a potential
      therapeutic target.

PMID- 19389854
TI  - Reactive immunization suppresses advanced glycation and mitigates diabetic
      nephropathy.
AB  - Agents that inhibit glycation end products by reducing the carbonyl load from
      glycation and glycoxidation are an emerging pharmacologic approach to treat
      complications of diabetes. We previously demonstrated that antibodies generated
      to the glycoprotein keyhole limpet hemocyanin (KLH) can cross-link with reactive
      carbonyl residues on protein conjugates. Here, we immunized streptozotocin
      induced diabetic rats with KLH to assess the capacity of the elicited antibodies
      to intercept carbonyl residues on glycated proteins and to mitigate glycation
      related pathology. Compared with diabetic rats immunized with adjuvant alone, KLH
      immunized diabetic rats had decreased levels of glycated peptides in sera and
      demonstrated a reduction in albuminuria, proteinuria, deposition of glycation end
      products in the kidney, and histologic damage. In vitro, low molecular weight
      glycated peptides from rat serum reacted with anti-KLH antibodies at a faster
      rate than normal IgG and selectively modified the lambda chains. The reaction
      products contained peptide sequences from type I collagen alpha chain, albumin,
      and LDL receptor-related protein. These adduction reactions were inhibited by
      free KLH and by reduction of glycated peptides with borohydride. In summary,
      these results suggest that inherent reactivity of Ig light chains provides a
      natural mechanism for the removal of cytotoxic glycation products. This
      reactivity can be augmented by glycoprotein-specific reactive immunization, a
      potential biopharmaceutical approach to glycation-related pathology.

PMID- 19389855
TI  - CCR5 deletion protects against inflammation-associated mortality in dialysis
      patients.
AB  - The CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory
      chemokines, and a deletion variant of the CCR5 gene (CCR5 Delta 32) leads to
      deficiency of the receptor. We hypothesized that CCR5 Delta 32 modulates
      inflammation-driven mortality in patients with ESRD. We studied the interaction
      between CCR5 genotype and levels of high-sensitivity C-reactive protein (hsCRP)
      in 603 incident dialysis patients from the multicenter, prospective NEtherlands
      COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort. CCR5 genotype and
      hsCRP levels were both available for 413 patients. During 5 yr of follow-up, 170
      patients died; 87 from cardiovascular causes. Compared with the reference group
      of patients who had the wild-type CCR5 genotype and hsCRP <or= 10 mg/L (n = 225),
      those carrying the deletion allele with hsCRP <or= 10 mg/L (n = 55) had similar
      mortality, and those carrying the wild-type genotype with hsCRP > 10 mg/L (n =
      108) had an increased risk for mortality (HR: 1.82; 95% CI: 1.29 to 2.58).
      However, those carrying the deletion allele with hsCRP > 10 mg/L (n = 25) had a
      mortality rate similar to the reference group; this seemingly protective effect
      of the CCR5 deletion was even more pronounced for cardiovascular mortality. We
      replicated these findings in an independent Swedish cohort of 302 ESRD patients.
      In conclusion, the CCR5 Delta 32 polymorphism attenuates the adverse effects of
      inflammation on overall and cardiovascular mortality in ESRD.

PMID- 19389856
TI  - Urine podocyte mRNAs mark progression of renal disease.
AB  - Because loss of podocytes associates with glomerulosclerosis, monitoring podocyte
      loss by measuring podocyte products in urine may be clinically useful. To
      determine whether a single episode of podocyte injury would cause persistent
      podocyte loss, we induced limited podocyte depletion using a diphtheria toxin
      receptor (hDTR) transgenic rat. We monitored podocyte loss by detecting nephrin
      and podocin mRNA in urine particulates with quantitative reverse transcriptase
      PCR. Aquaporin 2 mRNA served as a kidney reference gene to account for variable
      kidney contribution to RNA amount and quality. We found that a single injection
      of diphtheria toxin resulted in an initial peak of proteinuria and podocyte mRNAs
      (podocin and nephrin) followed 8 d later by a second peak of proteinuria and
      podocyte mRNAs that were podocin positive but nephrin negative. Proteinuria that
      persisted for months correlated with podocin-positive, nephrin-negative mRNAs in
      urine. Animals with persistent podocyte mRNA in urine progressed to ESRD with
      global podocyte depletion and interstitial scarring. Podocytes in ectatic tubules
      expressed podocalyxin and podocin proteins but not nephrin, compatible with
      detached podocytes' having an altered phenotype. Parallel human studies showed
      that biopsy-proven glomerular injury associated with increased urinary
      podocin:aquaporin 2 and nephrin:aquaporin 2 molar ratios. We conclude that a
      single episode of podocyte injury can trigger glomerular destabilization,
      resulting in persistent podocyte loss and an altered phenotype of podocytes
      recovered from urine. Podocyte mRNAs in urine may be a useful clinical tool for
      the diagnosis and monitoring of glomerular diseases.

PMID- 19389857
TI  - The drug of abuse gamma-hydroxybutyrate is a substrate for sodium-coupled
      monocarboxylate transporter (SMCT) 1 (SLC5A8): characterization of SMCT-mediated
      uptake and inhibition.
AB  - Gamma-hydroxybutyric acid (GHB), a drug of abuse, is a substrate of
      monocarboxylate transporters (MCTs). Sodium-coupled monocarboxylate transporter 1
      (SMCT1; SLC5A8) is expressed in kidney, thyroid gland, neurons, and intestinal
      tract and exhibits substrate specificity similar to that of the proton-dependent
      MCT (SLC16A) family. The role of SMCT1 in GHB disposition has not been
      determined. In this study we characterized the driving force, transport kinetics,
      and inhibitors of GHB uptake, as well as expression of SMCT and MCT isoforms, in
      rat thyroid follicular (FRTL-5) cells. GHB, as well as the monocarboxylates
      butyrate and d-lactate, exhibited sodium-dependent uptake at pH 7.4, which could
      be described with a simple Michaelis-Menten equation plus a diffusional component
      [K(m) 0.68 +/- 0.30 mM, V(max) 3.50 +/- 1.58 nmol . mg(-1) . min(-1), and
      diffusional clearance (P) 0.25 +/- 0.08 microl . mg(-1) . min(-1)]. In the
      absence of sodium, GHB uptake was significantly increased at lower pH, suggesting
      proton-gradient dependent transport. Reverse transcriptase-polymerase chain
      reaction and Western analyses demonstrated the expression of SMCT1, MCT1, and
      MCT2 in FRTL-5 cells, supporting the activity results. Sodium-dependent GHB
      uptake in FRTL-5 cells was inhibited by MCT substrates (d-lactate, l-lactate,
      pyruvate, and butyrate), nonsteroidal anti-inflammatory drugs (ibuprofen,
      ketoprofen, and naproxen), and probenecid. IC(50) values for l-lactate,
      ibuprofen, ketoprofen, and probenecid were 101, 31.6, 64.4, and 380 muM,
      respectively. All four inhibitors also significantly inhibited GHB uptake in rat
      MCT1 gene-transfected MDA/MB231 cells, suggesting they are not specific for
      SMCT1. Luteolin and alpha-cyano-4-hydroxycinnimate represent specific proton
      dependent MCT inhibitors. Our findings indicate that GHB is a substrate for both
      sodium- and proton-dependent MCTs and identified specific inhibitors of MCTs.

PMID- 19389858
TI  - The role of p-glycoprotein in limiting brain penetration of the peripherally
      acting anticholinergic overactive bladder drug trospium chloride.
AB  - The aim of the present study was to characterize the role of the drug-efflux
      transporter P-glycoprotein (P-gp) for the disposition of trospium chloride, a
      widely used anticholinergic drug for the treatment of overactive bladder. P-gp
      deficient mdr1a,b(-/-) knockout mice were given either 1 mg/kg trospium chloride
      orally or 1 mg/kg intravenously to analyze brain penetration, intestinal
      secretion, and hepatobiliary excretion of the drug. The concentrations of
      trospium chloride in the brain were up to 7 times higher in the mdr1a,b(-/-)
      knockout mice compared with wild-type mice (p < 0.05), making P-gp a limiting
      factor for the blood-brain barrier penetration of this drug. Moreover, the
      residence time of the drug in the central nervous system was significantly
      prolonged in mdr1a,b(-/-) knockout mice. Apart from the blood-brain barrier, P-gp
      also had significant effects on the overall pharmacokinetics of trospium
      chloride. In the mdr1a,b(-/-) knockout mice, hepatobiliary excretion and
      intestinal secretion were significantly reduced compared with the wild-type mice.
      Our study indicates that the multidrug resistance transporter P-gp is a major
      determinant for the distribution of trospium chloride in the body and highly
      restricts its entry into the brain.

PMID- 19389859
TI  - Pharmacokinetics of 5-fluorouracil in elderly Japanese patients with cancer
      treated with S-1 (a combination of tegafur and dihydropyrimidine dehydrogenase
      inhibitor 5-chloro-2,4-dihydroxypyridine).
AB  - S-1 is an oral anticancer agent that combines tegafur, a prodrug of 5
      fluorouracil (5-FU), and 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of
      dihydropyrimidine dehydrogenase. We examined the effects of aging on the
      pharmacokinetics of the components of S-1. The median area under the
      concentration-time curve (AUC) of active 5-FU did not significantly differ
      between 10 patients 75 years or older and 53 patients younger than 75 years (P =
      0.598, Mann-Whitney U test). It is interesting to note that the median oral
      clearance of tegafur in patients 75 years or older was significantly lower than
      that in patients younger than 75 years (P = 0.011). Furthermore, the median AUC
      of CDHP was significantly higher in patients 75 years or older than in those
      younger than 75 years (P = 0.004). This effect was caused by reduced renal
      function in the elderly, because CDHP is excreted in the urine by glomerular
      filtration. The opposing effects of aging on the oral clearance of tegafur and
      the AUC of CDHP may offset each other, leading to unchanged systemic exposure of
      5-FU.

PMID- 19389860
TI  - In vitro and in vivo induction of cytochrome p450: a survey of the current
      practices and recommendations: a pharmaceutical research and manufacturers of
      america perspective.
AB  - Cytochrome P450 (P450) induction is one of the factors that can affect the
      pharmacokinetics of a drug molecule upon multiple dosing, and it can result in
      pharmacokinetic drug-drug interactions with coadministered drugs causing
      potential therapeutic failures. In recent years, various in vitro assays have
      been developed and used routinely to assess the potential for drug-drug
      interactions due to P450 induction. There is a desire from the pharmaceutical
      industry and regulatory agencies to harmonize assay methodologies, data
      interpretation, and the design of clinical drug-drug interaction studies. In this
      article, a team of 10 scientists from nine Pharmaceutical Research and
      Manufacturers of America (PhRMA) member companies conducted an anonymous survey
      among PhRMA companies to query current practices with regards to the conduct of
      in vitro induction assays, data interpretation, and clinical induction study
      practices. The results of the survey are presented in this article, along with
      reviews of current methodologies of in vitro assays and in vivo studies,
      including modeling efforts in this area. A consensus recommendation regarding
      common practices for the conduct of P450 induction studies is included.

PMID- 19389861
TI  - Unbound brain concentration determines receptor occupancy: a correlation of drug
      concentration and brain serotonin and dopamine reuptake transporter occupancy for
      eighteen compounds in rats.
AB  - It is a commonly accepted hypothesis that central nervous system (CNS) activity
      is determined by the unbound brain drug concentration. However, limited
      experimental data are available in the literature to support this hypothesis. The
      objective of this study was to test this hypothesis by examining the relationship
      between in vitro binding affinity (K(I)) and in vivo activity quantified as the
      drug concentration occupying 50% of the transporters (OC(50)) for 18 serotonin
      (SERT) and dopamine transporter (DAT) inhibitors. In vivo rat OC(50) was
      determined by autoradiography using [(3)H]N,N-dimethyl-2,2-amino-4
      cyanophenylthiobenzylamine and [(3)H](-)-2-beta-carbomethoxy-3-beta-(4
      fluorophenyl)tropane-1,5-napthalenedisulfonate (WIN35,428) as the ligands to
      assess SERT and DAT occupancy, respectively. The unbound brain concentrations
      were calculated from total brain concentrations and the unbound brain fraction,
      which was determined by the brain homogenate method. The in vivo total brain SERT
      and DAT OC(50) values (mean +/- S.D.) were 408 +/- 368- and 410 +/- 395-fold
      greater than the K(I) values, respectively. In contrast, the in vivo unbound
      brain SERT and DAT OC(50) values were only 3.3 +/- 2.1- and 4.1 +/- 4.0-fold
      different from the K(I) values. Therefore, prediction of the biophase drug
      concentration by using the unbound brain concentration rather than the total
      brain concentration results in an approximately 100-fold improvement for the
      accuracy. In the present study, a 10-fold improvement was also observed by using
      the unbound plasma concentration rather than the total plasma concentration to
      predict the biophase concentration in the brain. This study supports the
      hypothesis that CNS activity is more accurately determined by the unbound brain
      drug concentration and not by the total brain drug concentration.

PMID- 19389862
TI  - Effects of Plantago ovata husk on levodopa (with Carbidopa) bioavailability in
      rabbits with autonomic gastrointestinal disorders.
AB  - Gastrointestinal dysfunction is common in Parkinson's disease. Fiber therapy
      could be used to reduce the symptoms of gastrointestinal motility disorders. In a
      previous study, we showed that slowed gastrointestinal motility modified levodopa
      pharmacokinetics: area under the plasma concentration-time curve (AUC) and
      maximum plasma concentration (C(max)) decreased and the elimination was delayed.
      In this study, we evaluated whether or not the hydrosoluble fiber Plantago ovata
      husk is useful in improving levodopa pharmacokinetics in rabbits with autonomic
      gastrointestinal disorders induced by the administration of the anticholinergic
      biperiden. Levodopa + carbidopa (20:5 mg/kg), biperiden (100 microg/kg), and P.
      ovata husk (at two different doses: 100 and 400 mg/kg) were administered orally
      to rabbits for two periods of time (7 or 14 days). In all groups of animals, the
      AUC values were approximately 50% higher on the final day of treatment than on
      day 1. C(max) was also higher, with the greater increase at the 400 mg/kg dose of
      fiber, which resulted in a boost of approximately 35%. On day 1 of treatment and
      with both doses of fiber, AUC values were very similar to those obtained in
      previous work in rabbits with normal gastrointestinal motility, but the C(max)
      was lower. However, after 7 or 14 days, the AUC values were higher, but C(max)
      remained lower. The greatest differences were observed in plasma concentration
      before drug administration (C(min)), for which the highest increase was obtained
      with the dose of 400 mg/kg fiber on day 14 of treatment (349.8%). P. ovata husk
      could be beneficial in patients with Parkinson's disease because it regulates
      stool transit in the intestine and because it improves levodopa pharmacokinetics
      when gastrointestinal peristalsis is slowed. These changes could lead to a
      possible delay in the onset of dyskinesias and to changes in prognosis.

PMID- 19389863
TI  - Who can afford to look to the future? The relationship between socio-economic
      status and proactive coping.
AB  - BACKGROUND: The aim of this article was to examine, whether middle-aged and older
      adults spontaneously engage in proactive coping to prevent future problems
      associated with ageing and whether differences in proactive coping were
      associated with socio-economic status (SES). METHODS: As part of the cross
      sectional Second Dutch National Survey of General Practice (DNSGP-2, 2001), a
      representative sample of 3189 adults aged 50-70 years filled in a questionnaire
      measuring proactive coping. In addition, data were collected regarding the three
      main components of SES, namely educational level, income and occupational status,
      as well as participants' health status. RESULTS: We found that higher SES,
      especially with respect to income and education, was positively associated with
      proactive coping. This relationship was not moderated, but was partially mediated
      by physical health problems. CONCLUSION: People with higher income and higher
      educational level used more proactive coping strategies in their daily life to
      offset potential problems associated with ageing. Physical health status
      partially explained the SES-differences in proactive coping. It seems that people
      with lower SES undertake less future-oriented activities as a result of the fact
      that present health problems require attention and drain resources.

PMID- 19389864
TI  - Glycaemic control in type 2 diabetic patients on chronic haemodialysis: use of a
      continuous glucose monitoring system.
AB  - BACKGROUND: The proportion of diabetic patients undergoing haemodialysis is
      rapidly increasing. Glucose control among such patients is difficult to assess.
      We aimed to evaluate the clinical performance of a continuous glucose monitoring
      system (CGMS) in type 2 diabetic patients on chronic haemodialysis. METHODS: We
      used a 4-day CGMS to monitor glucose levels in 19 haemodialysed type 2 diabetic
      patients (HD T2) including 2 days with and 2 days without dialysis session, and
      39 non-HD T2 in a double-centre study. RESULTS: The glucose concentration
      according to the glucose meter and CGMS were correlated in HD T2 patients (r =
      0.90, P < 0.0001) and in non-HD T2 patients (r = 0.81, P < 0.0001). The relative
      absolute difference (RAD) between glucose determined by a glucose meter and
      glucose determined by the CGMS did not differ between HD T2 and non-HD T2
      patients (9.2 +/- 10.5 vs. 8.2 +/- 7.6%; P = 0.165). Glycated haemoglobin (A1c)
      and mean glucose concentration were strongly correlated in non-HD T2 patients (r
      = 0.71; P < 0.0001) but weakly correlated in HD T2 patients (r = 0.47; P =
      0.042). Fructosamine was correlated with the mean glucose concentration in non-HD
      T2 (r = 0.67; P < 0.0001) but not in HD T2 patients (r = 0.04; P = 0.88).
      CONCLUSION: CGM is a validated marker of glycaemic control in HD diabetic
      patients. This tool showed that A1c and fructosamine, despite being good markers
      of glycaemic control in non-HD diabetic patients, are of poor value in HD
      diabetic patients.

PMID- 19389865
TI  - Active visfatin is elevated in serum of maintenance haemodialysis patients and
      correlates inversely with circulating HDL cholesterol.
AB  - BACKGROUND: Increased circulating visfatin may be associated both with
      endothelial damage and with increased mortality in end-stage renal disease
      (ESRD). HDL cholesterol is an independent, strong inverse predictor of
      cardiovascular events. However, associations between visfatin and parameters of
      lipid metabolism are unclear. Moreover, serum concentrations of visfatin measured
      by an enzyme immuno assay (EIA) are conflicting and do not correlate with ELISA
      (enzyme-linked immunosorbent assay) data, which predominantly detect
      enzymatically active visfatin. METHODS: A total of 74 haemodialysis (HD) patients
      and 35 control individuals (C) were studied. All subjects (mean age 62.9 years)
      provided fasted blood samples (HD patients after 66-69 h without dialysis).
      Circulating visfatin was measured by the ELISA. Body composition was evaluated
      using waist circumference, skinfold thickness and body impedance analysis.
      Results obtained by the ELISA were compared with EIA data. RESULTS: Active serum
      visfatin was increased in HD (5.58 +/- 6.50 ng/ml) versus C [0.97 +/- 1.79 ng/ml,
      mean +/- SD; P < 0.0001 by multiple regression analysis (MRA)] independently of
      plasma glucose, serum insulin, diabetes, HDL cholesterol and body composition.
      Within the HD group, only plasma HDL cholesterol (4% lower per additional mg/dl
      HDL; P = 0.001) and insulin-treated diabetes mellitus [subgroup of n = 18; 119%
      higher compared with patients without diabetes (n = 40); P = 0.011] were
      independently (by MRA) associated with active serum visfatin. Visfatin measured
      by an EIA showed no correlation with ELISA data. CONCLUSIONS: Our study provides
      reliable data on active visfatin in HD patients using a well-characterized ELISA.
      Loss of renal function is accompanied by increased circulating active visfatin
      concentrations in our patients. Furthermore, decreased HDL cholesterol may hint
      at an increased probability of cardiovascular events in HD patients with elevated
      serum visfatin.

PMID- 19389866
TI  - Effects of endurance training on extrarenal potassium regulation and exercise
      performance in patients on haemodialysis.
AB  - BACKGROUND: Haemodialysis patients (HDP) with anaemia display impaired plasma
      K(+) regulation during exercise and poor exercise performance. Epoetin treatment
      and exercise training improve exercise performance in HDP, but whether this is
      associated with improved K(+) regulation is unknown. METHODS: Six HDP with near
      normal [Hb] were tested for aerobic power ( ) and plasma [K(+)] during
      incremental exercise; quadriceps muscle strength (peak torque, PT) from 0 to 360
      degrees s(-1) and fatiguability (decline in strength during thirty contractions).
      Tests were conducted at baseline, after 6 weeks of normal activity (pre-train)
      and following 6 weeks cycle training (post-train). Six healthy untrained controls
      (CON) matched for age, sex, mass and height were tested at baseline. RESULTS: In
      HDP at baseline, and PT from 0 to 360 degrees s(-1) were respectively reduced by
      37% and 27-42%, compared to CON (P < 0.05). Plasma [K(+)], the rise in [K(+)]
      (Delta[K(+)]) and the Delta[K(+)] relative to total work done (Delta[K(+)] work(
      1) ratio) during incremental exercise were all higher in HDP at baseline compared
      to CON (P < 0.05). Exercise training increased time to fatigue by 12% (P < 0.05)
      but did not improve K(+) regulation or . An inverse correlation was found between
      the Delta[K(+)] work(-1) ratio and for pooled CON and HDP data. CONCLUSIONS: In
      HDP treated with epoetin, poor exercise performance was related to impaired
      extrarenal K(+) regulation, whilst training improved exercise performance but not
      K(+) regulation. Thus, although impaired extrarenal K(+) regulation may
      contribute to poor exercise performance in HDP, exercise performance can still
      improve with training despite unchanged K(+) regulation.

PMID- 19389867
TI  - Measuring lock solution spillage in-vivo versus in-vitro.

PMID- 19389868
TI  - The coronary artery disease SNP, rs4420638, is associated with diabetic
      nephropathy rather than end-stage renal disease.

PMID- 19389871
TI  - Antidiabetic Properties of Azardiracta indica and Bougainvillea spectabilis: In
      Vivo Studies in Murine Diabetes Model.
AB  - Diabetes mellitus is a metabolic syndrome characterized by an increase in the
      blood glucose level. Treatment of diabetes is complicated due to multifactorial
      nature of the disease. Azadirachta indica Adr. Juss and Bougainvillea spectabilis
      are reported to have medicinal values including antidiabetic properties. In the
      present study using invivo diabetic murine model, A. indica and B. spectabilis
      chloroform, methanolic and aqueous extracts were investigated for the biochemical
      parameters important for controlling diabetes. It was found that A. indica
      chloroform extract and B. spectabilis aqueous, methanolic extracts showed a good
      oral glucose tolerance and significantly reduced the intestinal glucosidase
      activity. Interestingly, A. indica chloroform and B. spectabilis aqueous extracts
      showed significant increase in glucose-6-phosphate dehydrogenase activity and
      hepatic, skeletal muscle glycogen content after 21 days of treatment. In
      immunohistochemical analysis, we observed a regeneration of insulin-producing
      cells and corresponding increase in the plasma insulin and c-peptide levels with
      the treatment of A. indica chloroform and B. spectabilis aqueous, methanolic
      extracts. Analyzing the results, it is clear that A. indica chloroform and B.
      spectabilis aqueous extracts are good candidates for developing new
      neutraceuticals treatment for diabetes.

PMID- 19389870
TI  - Decreased connectivity and cerebellar activity in autism during motor task
      performance.
AB  - Although motor deficits are common in autism, the neural correlates underlying
      the disruption of even basic motor execution are unknown. Motor deficits may be
      some of the earliest identifiable signs of abnormal development and increased
      understanding of their neural underpinnings may provide insight into autism
      associated differences in parallel systems critical for control of more complex
      behaviour necessary for social and communicative development. Functional magnetic
      resonance imaging was used to examine neural activation and connectivity during
      sequential, appositional finger tapping in 13 children, ages 8-12 years, with
      high-functioning autism (HFA) and 13 typically developing (TD), age- and sex
      matched peers. Both groups showed expected primary activations in cortical and
      subcortical regions associated with motor execution [contralateral primary
      sensorimotor cortex, contralateral thalamus, ipsilateral cerebellum,
      supplementary motor area (SMA)]; however, the TD group showed greater activation
      in the ipsilateral anterior cerebellum, while the HFA group showed greater
      activation in the SMA. Although activation differences were limited to a subset
      of regions, children with HFA demonstrated diffusely decreased connectivity
      across the motor execution network relative to control children. The between
      group dissociation of cerebral and cerebellar motor activation represents the
      first neuroimaging data of motor dysfunction in children with autism, providing
      insight into potentially abnormal circuits impacting development. Decreased
      cerebellar activation in the HFA group may reflect difficulty shifting motor
      execution from cortical regions associated with effortful control to regions
      associated with habitual execution. Additionally, diffusely decreased
      connectivity may reflect poor coordination within the circuit necessary for
      automating patterned motor behaviour. The findings might explain impairments in
      motor development in autism, as well as abnormal and delayed acquisition of
      gestures important for socialization and communication.

PMID- 19389872
TI  - Participation of functionally different macrophage populations and monocyte
      chemoattractant protein-1 in early stages of thioacetamide-induced rat hepatic
      injury.
AB  - Macrophages are crucial in hepatic fibrogenesis. In acute hepatic necrosis
      induced in rats by a single injection of 300 mg/kg body weight (BW) of
      thioacetamide (TAA), macrophage properties were investigated using single or
      double immunohistochemistry. Macrophages reacting with anti-CD68, anti-CD163, or
      major histocompatibility complex (anti-MHC) class II antibody appeared in injured
      centrilobular areas on days 1-5 after injection. Increased expression of CD68 and
      CD163 reflect phagocytosis and production of pro-inflammatory factors,
      respectively. There were also macrophages double-positive to CD68/CD163, CD68/MHC
      class II, or CD163/MHC class II; of these, macrophages double-positive to
      CD68/MHC class II were most frequent, indicating that macrophages with enhanced
      phagocytic activity came to express MHC class II. The appearance of these
      macrophages corresponded to increased expression of mRNAs of monocyte
      chemoattractant protein-1 (MCP-1), a chemokine, on day 1, and TGF-beta1, a
      fibrogenic factor, on day 3. Some hepatic stellate cells (HSCs) in injured areas
      reacted with anti-MCP-1 antibody. To investigate the effects of MCP-1, we added
      MCP-1 to HS-P, a rat macrophage line. Addition of MCP-1 increased
      immunoexpression for CD68 and CD163 and up-regulated TGF-beta1 mRNA expression.
      Collectively, macrophages in acute hepatic necrosis may express different
      properties such as phagocytosis, MHC class II expression, and TGF-beta1
      production; such expression may be influenced by MCP-1 produced by HSCs.

PMID- 19389873
TI  - Molecular expression analysis of beta-naphthoflavone-induced hepatocellular
      tumors in rats.
AB  - The present study was performed to characterize molecular expression levels of
      preneoplastic and neoplastic lesions induced by beta-naphthoflavone (BNF), an
      aryl hydrocarbon receptor (AhR) agonist in rat hepatocarcinogenesis. Male F344
      rats were initiated with an intraperitoneal injection of 200 mg/kg N
      diethylnitrosamine, and two weeks later, they were fed a diet containing 0% or 1%
      BNF for twenty-eight weeks. All animals were subjected to a two-thirds partial
      hepatectomy at week 3 and sacrificed at week 30. Histopathologically, BNF
      increased the incidence and multiplicity of altered foci (1.7-fold and 3.3-fold)
      and hepatocellular adenomas (HCAs) (4.0-fold and 4.7-fold).
      Immunohistochemically, BNF increased the number of proliferating cell nuclear
      antigen (PCNA)-positive cells in altered foci (2.3-fold) and HCAs (6.7-fold)
      compared with the surrounding tissue and decreased the staining of cell cycle
      regulators (P21, C/EBPalpha). In addition, loss of reactivity for AhR-regulated
      (CYP1A1, CYP1B1) molecules and increased reactivity of Nrf-2-regulated (AKR7,
      GPX2) molecules were also observed in proliferative lesions. Furthermore,
      increased staining of histone deacetylase (HDAC1) in the nucleus was prominent in
      HCAs. The differential expression patterns were confirmed at mRNA levels by real
      time reverse transcription-polymerase chain reaction (RT-PCR) analysis. These
      results suggest that enhanced cell proliferation and protection against oxidative
      stress play an important role in BNF-induced hepatocarcinogenesis in rats.

PMID- 19389874
TI  - Gamma-tocopherol attenuates ozone-induced exacerbation of allergic rhinosinusitis
      in rats.
AB  - Compared to healthy subjects, individuals with allergic airway disease (e.g.,
      asthma, allergic rhinitis) have enhanced inflammatory responses to inhaled ozone.
      We created a rodent model of ozone-enhanced allergic nasal responses in Brown
      Norway rats to test the therapeutic effects of the dietary supplement gamma
      tocopherol (gammaT). Ovalbumin (OVA)-sensitized rats were intranasally challenged
      with 0% or 0.5% OVA (in saline) on Days 1 and 2, and then exposed to 0 or 1 ppm
      ozone (eight hours/day) on Days 4 and 5. Rats were also given 0 or 100 mg/kg
      gammaT (p.o., in corn oil) on days 2 through 5, beginning twelve hours after the
      last OVA challenge. On Day 6, nasal tissues were collected for histological
      evaluation and morphometric analyses of intraepithelial mucosubstances (IM) and
      eosinophilic inflammation. Nasal septal tissue was microdissected and analyzed by
      reverse transcriptase polymerase chain reaction (RT-PCR) for mucin glycoprotein
      5AC (MUC5AC) expression levels. Histological analysis revealed mild to moderate
      eosinophil influx in the mucosa lining the nasal airways and maxillary sinus of
      OVA-challenged rats (eosinophilic rhinosinusitis). Ozone exposure of allergic
      rats further increased eosinophils in the maxillary sinus (400%), nasolacrimal
      duct (250%), and proximal midseptum (150%). Storage of intraepithelial
      mucosubstances (IM) was not significantly affected by OVA challenge in filtered
      air-exposed rats, but it was increased by ozone in the septum (45%) and maxillary
      sinus (55%) of allergic compared to control rats. Treatment with gammaT
      attenuated the ozone/ OVA-induced synergistic increases in IM and mucosal
      eosinophils in both nasal and paranasal airways. gamma-Tocopherol also blocked
      OVA and ozone-induced MUC5AC gene expression. Together, these data describe a
      unique model of ozone enhancement of allergic rhinosinusitis and the novel
      therapeutic efficacy of a common supplement, gammaT, to inhibit ozone
      exacerbation of allergic airway responses.

PMID- 19389875
TI  - Intervening on risk factors for coronary heart disease: an application of the
      parametric g-formula.
AB  - Estimating the population risk of disease under hypothetical interventions--such
      as the population risk of coronary heart disease (CHD) were everyone to quit
      smoking and start exercising or to start exercising if diagnosed with diabetes-
      may not be possible using standard analytic techniques. The parametric g-formula,
      which appropriately adjusts for time-varying confounders affected by prior
      exposures, is especially well suited to estimating effects when the intervention
      involves multiple factors (joint interventions) or when the intervention involves
      decisions that depend on the value of evolving time-dependent factors (dynamic
      interventions). We describe the parametric g-formula, and use it to estimate the
      effect of various hypothetical lifestyle interventions on the risk of CHD using
      data from the Nurses' Health Study. Over the period 1982-2002, the 20-year risk
      of CHD in this cohort was 3.50%. Under a joint intervention of no smoking,
      increased exercise, improved diet, moderate alcohol consumption and reduced body
      mass index, the estimated risk was 1.89% (95% confidence interval: 1.46-2.41). We
      discuss whether the assumptions required for the validity of the parametric g
      formula hold in the Nurses' Health Study data. This work represents the first
      large-scale application of the parametric g-formula in an epidemiologic cohort
      study.

PMID- 19389876
TI  - Effect of ketoconazole on the pharmacokinetic profile of ambrisentan.
AB  - Ambrisentan is an endothelin type A (ET(A))-selective receptor antagonist that is
      metabolized primarily by glucuronidation but also undergoes oxidative metabolism
      by CYP3A4. The potential for ketoconazole, the archetypal strong inhibitor of
      CYP3A4, to alter the pharmacokinetic profile of ambrisentan and its oxidative
      metabolite, 4-hydroxymethyl ambrisentan, was assessed in an open-label,
      nonrandomized, 2-period, single-sequence study in 16 healthy men. Participants
      received a single dose of ambrisentan 10 mg alone and after 4 days of
      ketoconazole 400 mg administered once daily. In the presence of multiple doses of
      ketoconazole, single-dose ambrisentan AUC(0-infinity) estimate was increased by
      35.3%, whereas C(max) was increased by 20.0%. For the 4-hydroxymethyl ambrisentan
      metabolite, AUC(0-infinity) estimate was decreased by 4.0%, whereas C(max) was
      decreased by 16.5%. Concomitant administration of ambrisentan and ketoconazole
      was well tolerated. In summary, ketoconazole had no clinically significant effect
      on the pharmacokinetics or safety profile of ambrisentan; therefore, no changes
      in ambrisentan dose should be necessary when the drug is administered
      concomitantly with known CYP3A4 inhibitors.

PMID- 19389877
TI  - Pharmacokinetic, pharmacodynamic, and electrocardiographic effects of dapoxetine
      and moxifloxacin compared with placebo in healthy adult male subjects.
AB  - Selective serotonin reuptake inhibitors (SSRIs) may be associated with
      electrocardiographic effects. The electrocardiographic pharmacodynamics of
      dapoxetine, a short-acting SSRI being developed for the treatment of premature
      ejaculation, are compared with those of placebo and moxifloxacin (positive
      control) in 2 single-center, randomized, crossover studies in healthy men. In
      study 1, subjects receive 2 doses of dapoxetine 120 mg, given 3 hours apart; a
      single dose of moxifloxacin 400 mg; and 2 doses of placebo, given 3 hours apart.
      In study 2, subjects receive single doses of dapoxetine 60 mg, dapoxetine 120 mg,
      moxifloxacin 400 mg, and placebo. Moxifloxacin significantly increases QT and
      corrects QT intervals (QTc) compared with placebo in both studies (eg, Bazett
      corrected QTc of 11.90 milliseconds [95% confidence interval, 2.68 to 21.11] and
      5.06 [95% confidence interval, -2.26 to 12.38]). Dapoxetine 60, 120, and 240 mg
      do not prolong the QT/QTc interval and have no clinically significant
      electrocardiographic effects. Dapoxetine and moxifloxacin pharmacokinetics are
      similar to previous reports. Adverse events are generally mild in severity;
      nausea is the most common. The results demonstrate that dapoxetine does not have
      electrocardiographic effects at doses of 60, 120, and 240 mg.

PMID- 19389878
TI  - Pralatrexate-induced tumor cell apoptosis in the epidermis of a patient with HTLV
      1 adult T-cell lymphoma/leukemia causing skin erosions.
AB  - Pralatrexate is a novel antifolate, which shows increased antitumor activity in
      human tumor xenograft studies in mice compared with methotrexate. We investigated
      the effects of pralatrexate in a patient with adult T-cell lymphoma/leukemia with
      significant skin involvement. Atypical lymphocytes in epidermal Pautrier
      microabscesses were positive for HTLV-1. After the patient presented with
      leukemic conversion and with worsening of an erythematous generalized papular
      rash, he received one dose of pralatrexate. Within one week, his skin developed
      innumerable small erosions limited to the areas of the papular rash, sparing
      unaffected skin. Here we present in vivo evidence that pralatrexate-induced
      erosions in skin affected by adult T-cell lymphoma/leukemia are a manifestation
      of apoptosis of tumor cells infiltrating the epidermis and are not the result of
      cytotoxicity by pralatrexate on keratinocytes. This distinction is critical and
      may profoundly influence the clinical decision to continue pralatrexate
      treatment. Pralatrexate-induced skin erosions may indicate response to treatment.

PMID- 19389880
TI  - A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1)
      peptide vaccination in patients with AML and MDS.
AB  - This study investigated the immunogenicity of Wilms tumor gene product 1 (WT1)
      peptide vaccination in WT1-expressing acute myeloid leukemia (AML) and
      myelodysplastic syndrome (MDS) patients without curative treatment option.
      Vaccination consisted of granulocyte-macrophage colony-stimulating factor
      subcutaneously days 1 to 4, and WT1.126-134 peptide and 1 mg keyhole limpet
      hemocyanin on day 3. The initial 9 patients received 4 vaccinations biweekly,
      then monthly, and the subsequent 10 patients received continual biweekly
      vaccination. Seventeen AML patients and 2 refractory anemia with excess blasts
      patients received a median of 11 vaccinations. Treatment was well tolerated.
      Objective responses in AML patients were 10 stable diseases (SDs) including 4 SDs
      with more than 50% blast reduction and 2 with hematologic improvement. An
      additional 4 patients had clinical benefit after initial progression, including 1
      complete remission and 3 SDs. WT1 mRNA levels decreased at least 3-fold from
      baseline in 35% of patients. In 8 of 18 patients, WT1-tetramer(+) T cells
      increased in blood and in 8 of 17 patients in bone marrow, with a median
      frequency in bone marrow of 0.18% at baseline and 0.41% in week 18. This WT1
      vaccination study provides immunologic, molecular, and preliminary evidence of
      potential clinical efficacy in AML patients, warranting further investigations.

PMID- 19389879
TI  - Compassionate use of sorafenib in FLT3-ITD-positive acute myeloid leukemia:
      sustained regression before and after allogeneic stem cell transplantation.
AB  - Acute myeloid leukemia (AML) patients with internal tandem duplication (ITD)
      mutations in the Fms-like tyrosine-3 (FLT3) gene have a dismal prognosis. Here we
      report compassionate-use results with the multikinase and FLT3-ITD inhibitor
      sorafenib for the treatment of relapsed or refractory FLT3-ITD-positive AML.
      Sorafenib induced clinically meaningful and very rapid responses in all 6
      patients treated either before (n = 2), after (n = 3), or both before and after
      (n = 1) allogeneic stem cell transplantation (allo-SCT). Sorafenib-induced
      remissions facilitated allo-SCT in 2 of the 3 refractory patients. Two of the 4
      patients who were treated after allo-SCT survived 216 and 221 days, respectively,
      whereas the other 2 remain in ongoing complete molecular remission. Sorafenib
      response was associated with an inhibition of the antiapoptotic FLT3-ITD target
      Stat-5 in vivo. Together, sorafenib monotherapy before or after allo-SCT has
      remarkable clinical activity in poor risk FLT3-ITD-positive AML and deserves
      further evaluation in prospective clinical trials.

PMID- 19389881
TI  - Gene expression profiling of plasma cells at myeloma relapse from tandem
      transplantation trial Total Therapy 2 predicts subsequent survival.
AB  - We report on prognostic implications for post-relapse survival (PRS) of a gene
      expression profiling (GEP)-defined risk score at relapse available in 120 myeloma
      patients previously enrolled in tandem transplantation trial Total Therapy 2.
      Among the 71 patients with additional GEP baseline information, 3-year PRS was
      71% in 40 patients with low risk present both at baseline and relapse contrasting
      with only 17% in 28 patients with high risk at relapse, 12 of whom with baseline
      low-risk status fared better than the remainder (P = .08). On multivariate
      analysis of relapse parameters available in 104 patients, high risk conferred
      short PRS (hazard ratio = 4.00, P < .001, R(2) = 33%), whereas relapse
      hyperdiploidy predicted long PRS (hazard ratio = 0.37, P = .022, cumulative R(2)
      = 41%). In case the initial partial response lasted less than 2 years, relapse
      low-risk identified 26 patients with superior 3-year PRS of 61% versus 9% among
      32 with relapse high-risk (P < .001). Based on its PRS predictive power, GEP
      analysis should be an integral part of new agent trials in search of better
      therapy for high-risk myeloma.

PMID- 19389882
TI  - Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and
      HIV-suppressive activity.
AB  - CD8(+) T cells are major players in the immune response against HIV. However,
      recent failures in the development of T cell-based vaccines against HIV-1 have
      emphasized the need to reassess our basic knowledge of T cell-mediated efficacy.
      CD8(+) T cells from HIV-1-infected patients with slow disease progression exhibit
      potent polyfunctionality and HIV-suppressive activity, yet the factors that unify
      these properties are incompletely understood. We performed a detailed study of
      the interplay between T-cell functional attributes using a bank of HIV-specific
      CD8(+) T-cell clones isolated in vitro; this approach enabled us to overcome
      inherent difficulties related to the in vivo heterogeneity of T-cell populations
      and address the underlying determinants that synthesize the qualities required
      for antiviral efficacy. Conclusions were supported by ex vivo analysis of HIV
      specific CD8(+) T cells from infected donors. We report that attributes of CD8(+)
      T-cell efficacy against HIV are linked at the level of antigen sensitivity.
      Highly sensitive CD8(+) T cells display polyfunctional profiles and potent HIV
      suppressive activity. These data provide new insights into the mechanisms
      underlying CD8(+) T-cell efficacy against HIV, and indicate that vaccine
      strategies should focus on the induction of HIV-specific T cells with high levels
      of antigen sensitivity to elicit potent antiviral efficacy.

PMID- 19389883
TI  - Salivary steroid assays: still awaiting a killer application.

PMID- 19389884
TI  - How should proteinuria be detected and measured?
AB  - Proteinuria is a classic sign of kidney disease and its presence carries powerful
      prognostic information. Although proteinuria testing is enshrined in clinical
      practice guidelines, there is surprising variation among such guidelines as to
      the definition of clinically significant proteinuria. There is also poor
      agreement as to whether proteinuria should be defined in terms of albumin or
      total protein loss, with a different approach being used to stratify diabetic and
      non-diabetic nephropathy. Further, the role of reagent strip devices in the
      detection and assessment of proteinuria is unclear. This review explores these
      issues in relation to recent national and international guidelines on chronic
      kidney disease (CKD) and epidemiological evidence linking proteinuria and
      clinical outcome. The authors argue that use of urinary albumin measurement as
      the front-line test for proteinuria detection offers the best chance of improving
      the sensitivity, quality and consistency of approach to the early detection and
      management of CKD.

PMID- 19389885
TI  - The mean and the biological variation of insulin resistance does not differ
      between polycystic ovary syndrome and type 2 diabetes.
AB  - BACKGROUND: There is an assumption that the mean and biological variation of
      insulin resistance (IR) is less in polycystic ovary syndrome (PCOS), and
      intuitively higher in type 2 diabetes (T2DM). To test this hypothesis we compared
      the mean and biological variation in IR in PCOS to that of T2DM and to age- and
      weight-matched controls. METHODS: Twelve PCOS, 11 matched healthy women; 12
      postmenopausal diet-controlled T2DM and 11 matched healthy postmenopausal women
      were recruited. Blood samples were collected at 4-d intervals on 10 consecutive
      occasions. The biological variability of IR was derived on duplicate samples.
      RESULTS: Mean and biological variability of HOMA-IR for PCOS did not differ from
      T2DM. Both measures were higher than the matched controls. There was no
      difference in insulin or IR measures between the body mass index matched pre- and
      postmenopausal women. Percentage beta cell function were 208.8%, 62.3%, 106.5%
      and 111.9%, respectively, in PCOS, postmenopausal women with T2DM, healthy
      premenopausal and healthy postmenopausal women. CONCLUSIONS: The progression from
      PCOS to the development of T2DM is unlikely to be due to a further increase in IR
      (or variability), but rather the progressive failure of pancreatic beta cells
      with a decrease in insulin production. The clinical trial registration number for
      this study is ISRCTN65353256.

PMID- 19389886
TI  - A simple automated solid-phase extraction procedure for measurement of 25
      hydroxyvitamin D3 and D2 by liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Measurement of 25-hydroxyvitamin D(3) (25OHD(3)) and D(2) (25OHD(2))
      is challenging. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods
      have been described but they are often complex and difficult to automate. We have
      developed a simplified procedure involving an automated solid-phase extraction
      (SPE). METHODS: Internal standard (hexadeuterated 25-hydroxyvitamin D(3)) was
      added to serum or plasma followed by protein precipitation with methanol.
      Following centrifugation, a robotic instrument (CTC PAL [Presearch] for ITSP SPE
      [MicroLiter Analytical Supplies, Inc]) performed a six-step SPE procedure and the
      purified samples were injected into the LC-MS/MS. Quantification of 25OHD(3) and
      25OHD(2) was by electrospray ionization MS/MS in the multiple-reaction monitoring
      mode. RESULTS: The lower limit of quantitation was 4.0 nmol/L for 25OHD(3) and
      7.5 nmol/L for 25OHD(2). Within- and between-assay precision was below 10% over
      the concentration range of 22.5-120 nmol/L for D(3) and 17.5-70 nmol/L for D(2)
      (n = 10). The calibration was linear up to 2500 nmol/L (r = 0.99). Recoveries
      ranged between 89% and 104% for both metabolites and no ion suppression was
      observed. The results obtained compared well (r = 0.96) with the IDS-OCTEIA 25
      hydroxyvitamin D enzyme immunoassay for samples containing less than 125 nmol/L,
      at higher concentrations the immunodiagnostic system (IDS) method showed positive
      bias. CONCLUSIONS: Our simplified sample preparation and automated SPE method is
      suitable for the measurement of 25OHD(3) and D(2) in a routine laboratory
      environment. The system can process up to 300 samples per day with no cumbersome
      solvent evaporation step and minimal operator intervention.

PMID- 19389887
TI  - Ischaemia-modified albumin in dilated cardiomyopathy.
AB  - BACKGROUND: Biomarkers of myocardial necrosis may be increased in patients with
      chronic heart failure. We investigated whether ischaemia-modified albumin (IMA),
      a marker of ischaemia, is also elevated in patients with compensated heart
      failure, due to dilated cardiomyopathy (DCM). METHODS: We studied 42 patients
      with DCM and an equal number of age-matched normal volunteers. We assessed IMA
      serum levels with the albumin cobalt binding test. RESULTS: IMA was 89.9 +/- 13.1
      (71-117) KU/L in the patient group and 93.9 +/- 9.9 (76-122) KU/L in the control
      group, with no significant difference between the two (P = 0.11). However, IMA
      differed significantly according to the New York Heart Association classification
      (P = 0.003) and was negatively correlated with the left ventricular ejection
      fraction (r = -0.40, P = 0.014). CONCLUSIONS: We conclude that IMA, a marker of
      ischaemia, does not differ in patients with clinically stable DCM compared with
      normal subjects, but varies significantly in relation to the severity of the
      disease.

PMID- 19389888
TI  - A prospective study of causes of haemolysis during venepuncture: tourniquet time
      should be kept to a minimum.
AB  - BACKGROUND: Haemolysis is defined as the release of cellular components of
      erythrocytes and other blood cells into the extracellular space of blood. These
      cellular components can cause interference in laboratory measurements, potassium
      being a commonly measured analyte to be affected. A number of factors have been
      implicated in the aetiology of haemolysis. We undertook this study to enable us
      to identify and hence rectify causes of haemolysis in samples from patients on
      acute medical and surgical wards. METHODS: We performed a prospective study of
      353 blood sampling events during February and March 2007. A proforma was used to
      obtain detailed information of each blood-taking episode. Information from the
      proforma was linked to the incidence of haemolysis obtained from the hospital
      computer system. RESULTS: The incidence of haemolysis among the samples studied
      was 6.5%. While staff group, method of sampling, tourniquet time and number of
      attempts at venepuncture were each univariately associated with haemolysis,
      stepwise logistic regression resulted in a final model which only included
      tourniquet time (odds ratio for haemolysis if tourniquet time >1 min was 19.5
      [95% confidence interval [CI] 5.6-67.4%]). CONCLUSION: Tourniquet time of more
      than a minute is associated with a significant increase in risk of haemolysis.
      Advice on tourniquet time is included in phlebotomy training within the hospital;
      hence a campaign of appropriately channelled continuing education on this issue
      may be successful in reducing the haemolysis rate.

PMID- 19389889
TI  - Molecular mimicry and immune thrombocytopenia.

PMID- 19389890
TI  - REVelation (del: 5q).

PMID- 19389891
TI  - Fathoming flt3.

PMID- 19389892
TI  - Relative contribution of VKORC1, CYP2C9, and INR response to warfarin stable
      dose.

PMID- 19389893
TI  - Referral of patients with thrombocytopenia from primary care clinicians to
      hematologists.

PMID- 19389894
TI  - Doppler velocimetry of the ophthalmic artery in normal pregnancy: reference
      values.
AB  - OBJECTIVE: This study aimed at analyzing the correlation between ophthalmic
      Doppler indices and gestational age (GA) in healthy patients with singleton
      pregnancies. Intraobserver reproducibility and right-to-left eye correlation were
      also evaluated. METHODS: Healthy pregnant women (n = 289) at 20 to 40 weeks' GA
      were evaluated. The resistive index (RI), pulsatility index (PI), and peak ratio
      (PR) were determined by 2 measurements in each eye. Comparisons were performed
      first between the 2 measurements in each eye and later between the right and left
      eyes. Spearman rank correlation was used to analyze the relationship of the RI,
      PI, and PR with GA. Linear regression analysis was also performed. RESULTS: No
      significant differences were found between the values obtained for the first and
      the second measurements in each eye and those for the RI, PI, and PR in the right
      and left eyes. There was a significant decrease in RI and PI values with
      advancing GA, however (rho = -0.264 and -0.1192, respectively), with low R(2)
      values for both. Thus, only a small proportion of the variations observed in the
      RI and PI was associated with changes in GA. No significant difference was found
      between the PR values with regard to GA intervals. CONCLUSIONS: Doppler
      velocimetry is a reproducible technique for evaluation of the RI, PI, and PR in
      the ophthalmic artery. Unilateral analysis of these indices can be used. Linear
      regression analysis indicated that other factors were associated with a decrease
      in the RI and PI values with advancing GA. No significant change was observed in
      the PR values throughout normal pregnancy.

PMID- 19389895
TI  - Advantages of 3-dimensional sonography in embryo transfer.
AB  - OBJECTIVE: The purpose of this study was to investigate the advantages of 3
      dimensional (3D) sonography in embryo transfer. METHODS: With the use of 2
      dimensional (2D) and 3D sonography to measure the transfer distance from the
      fundus (TDF), 319 patients were allocated into 4 groups according to the
      disparity between 2D and 3D images: group 1 showed disparity of less than 3 mm;
      group 2 showed disparity of 3 to 5 mm; group 3 showed disparity of 6 to 9 mm; and
      group 4 showed disparity of 10 mm or greater. The general characteristics and
      pregnancy outcomes were compared among the 4 groups. RESULTS: For 140 patients,
      the TDF measured by 2D sonography was different from that measured by 3D
      sonography, with a positive to negative range of 3 to 13 mm. Compared with the
      first 3 groups, the clinical pregnancy and implantation rates were lowest in
      group 4 (7.7% versus 34.1%, 38.1%, and 40%; 3.6% versus 18.2%, 21.2%, and 22.2%;
      P < .05). CONCLUSIONS: Compared with 2D sonography, uterine cavity and catheter
      placement may be better achieved with 3D sonography, which would improve the
      embryo transfer technique.

PMID- 19389896
TI  - Sonographic appearances of the endometrium after termination of pregnancy in
      asymptomatic versus symptomatic women.
AB  - OBJECTIVE: The purpose of this study was to describe normal sonographic
      appearances of the endometrium in asymptomatic women after elective termination
      of pregnancy (TOP) and to determine whether sonographic findings are
      discriminatory in symptomatic women after TOP. METHODS: Sonographic parameters
      were compared in prospectively recruited women after elective TOP. The first 38
      were asymptomatic. In a later group, 105 had symptoms suggestive of retained
      products of conception (RPOC). Endometrial thickness, cavity irregularity,
      echogenicity of cavity contents, color Doppler flow, and resistive indices (RIs)
      were assessed. In the symptomatic group, sonographic findings were correlated
      with symptoms and histologic results. RESULTS: There was a marked overlap in
      sonographic appearances between the groups. The endometrial cavity is commonly
      irregular and thickened and may show prominent color Doppler flow in women with
      an uneventful course as well as in women with histologically proven RPOC.
      Differences between asymptomatic and symptomatic women were only seen for:
      endometrial thickness (10.8 mm [range, 1-29 mm] versus 15.3 mm [range, 1.8-34
      mm]; P = .0005), and cavity irregularity was greater in symptomatic women (P =
      .001). Color Doppler flow mean RIs were similar. Symptoms were similar in women
      proceeding to curettage versus no curettage; no significant relationship was
      found between individual symptoms and sonographic parameters. Chorionic villi
      were seen in 47 of 56 women (84%) with positive histologic results. CONCLUSIONS:
      Sonographic appearances and symptoms correlate poorly with each other and with
      histologic results. Sonography has limited benefits in triaging women with
      suspected RPOC after TOP in the first trimester. Our findings support a more
      conservative approach to suspected RPOC after TOP.

PMID- 19389898
TI  - Quality of 2- and 3-dimensional fast acquisition fetal cardiac imaging at 18 to
      22 weeks: ramifications for screening.
AB  - OBJECTIVE: The purpose of this study was to evaluate the frequency with which 6
      different fetal cardiac views taken during a fetal ultrasound examination at 18
      to 22 weeks' gestation can be obtained satisfactorily for cardiac anomaly
      screening using either a 2-dimensional (2D) static or 3-dimensional (3D) fast
      acquisition technique. METHODS: A prospective study of 100 low-risk women
      undergoing an anatomic survey was performed. Standard static 2D and 3D fast
      acquisition volumes were obtained on all patients. The 2D and 3D images were
      assigned, in a random order, to be independently graded by 3 reviewers. The
      degree of inter-reviewer agreement was assessed through the use of the Cohen
      kappa statistic. The factors contributing to satisfactory imaging were evaluated
      by random effects logistic regression. RESULTS: A significant proportion of both
      2D and 3D images were judged unsatisfactory for screening purposes. However, 2D
      images were significantly more likely, for all cardiac views, to be judged
      satisfactory (P < .05). The odds ratios for the 2D technique's being more likely
      than the 3D technique to provide images satisfactory for screening were 2.6 for
      the 4-chamber view, 2.4 for the right ventricular outflow tract, 4 for the left
      ventricular outflow tract, 3.2 for the 3-vessel view, 8.6 for the aortic arch,
      and 2.2 for the ductal arch. CONCLUSIONS: In this prospective study, static 2D
      imaging was significantly more likely than fast acquisition 2D imaging to yield
      cardiac views of high enough quality to satisfactorily screen for anomalies.

PMID- 19389897
TI  - Ovarian stromal hyperthecosis: sonographic features and histologic associations.
AB  - OBJECTIVE: Ovarian stromal hyperthecosis (SH) has variable clinical importance
      but can cause hyperandrogenism, particularly in premenopausal women. Sonography
      is often used to evaluate the ovaries of women with hyperandrogenism, but there
      is little published regarding the sonographic appearance of SH. The primary
      purpose of this study was to describe the sonographic features of SH. METHODS: A
      computerized search of our institution's pathology and imaging databases from
      1996 through 2007 was performed to identify patients with histologically proven
      SH who had pelvic sonography before surgery. Sonograms and histologic findings
      were reviewed in each case. RESULTS: Twenty ovaries with SH were identified,
      occurring in 14 patients with a mean age of 59.8 years (range, 36-83 years). The
      SH was bilateral in 6 patients, unilateral in 6, and of uncertain laterality in 2
      with a unilateral oophorectomy. Sonographic findings were as follows: 5 normal, 1
      with a hemorrhagic cyst (later resolved) and otherwise normal, 3 enlarged but
      otherwise normal, 1 with a solid mass due to the nodular form of SH, 1 with a
      solid mass due to a fibroma, 2 with polycystic ovaries, and 7 not seen. Six of
      the 14 patients (43%) also had an ovarian fibrothecoma. CONCLUSIONS: Ovarian SH
      has variable sonographic features. Most commonly, the affected ovaries are either
      normal or slightly enlarged. A solid mass may infrequently be visible, and
      polycystic ovary syndrome changes may coexist with SH. A possible association of
      SH with fibrothecoma was also noted, which to our knowledge has not been
      previously reported.

PMID- 19389899
TI  - Utility of fetal echocardiography after normal cardiac imaging findings on
      detailed fetal anatomic ultrasonography.
AB  - OBJECTIVE: The purpose of this study was to assess the utility of fetal
      echocardiography (FE) after normal fetal cardiac imaging findings during detailed
      fetal anatomic ultrasonography (FAU). METHODS: We conducted a retrospective
      cohort review of obstetric ultrasonographic studies from November 2001 through
      July 2005. We identified women with a singleton gestation with increased risk for
      congenital heart disease who received FAU performed by a maternal-fetal medicine
      specialist at 16 to 20 weeks' gestation with subsequent FE. These records were
      compared with newborn outcomes. RESULTS: Of 789 pregnancies that had FAU and FE,
      481 had satisfactory cardiac imaging. Of those, only 1 fetus had abnormal FE
      findings. After delivery, 4 of the 480 neonates with normal FAU and FE findings
      had a diagnosis of a heart defect. CONCLUSIONS: Fetal echocardiography does not
      substantially increase the detection rate of major cardiac anomalies after normal
      findings on detailed FAU performed by a maternal-fetal medicine specialist.

PMID- 19389900
TI  - Embryonic heart rate as a prognostic factor for chromosomal abnormalities.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of a slow embryonic
      heart rate in embryos before 7 weeks' gestation as a marker in screening for
      chromosomal abnormalities. METHODS: Fifty-seven embryos before 7 weeks' gestation
      with slow heart rates were compared with 1156 embryos of the same gestational
      period with normal heart rates. Embryos that showed an increased risk of
      chromosomal abnormalities in the screening blood tests underwent invasive
      analysis for abnormal karyotype detection. RESULTS: The rates of first-trimester
      death were 15.8% for pregnancies with slow embryonic heart rates (9 of 57) and
      2.5% for those with normal heart rates (29 of 1156). Because of the increased
      risk of chromosomal abnormalities, amniocentesis was performed on 6 with slow
      embryonic heart rates and 61 with normal embryonic heart rates. After karyotype
      analysis, there were 2 fetuses with trisomy 21 in each group, which represented
      significantly higher percentage of embryos with trisomy 21 in the slow-heart rate
      group compared with the normal-heart rate group (P < .05). CONCLUSIONS: When a
      slow embryonic heart rate is detected before 7 weeks' gestation, there is a
      higher likelihood of chromosomal abnormalities.

PMID- 19389901
TI  - Sonographic fetal weight estimation: which model should be used?
AB  - OBJECTIVE: The purpose of this study was to compare the accuracy of different
      sonographic models for fetal weight estimation. METHODS: We evaluated 26
      different models using 3705 sonographic weight estimations performed less than 3
      days before delivery. Models were ranked on the basis of systematic and random
      errors and were grouped according to the combination of biometric indices in each
      model. Cluster analysis was used to compare the accuracy of the different model
      groups. RESULTS: A considerable variation in the accuracy of the different models
      was found. For birth weights (BWs) in the range of 1000 to 4500 g, models based
      on 3 or 4 fetal biometric indices were significantly more accurate than models
      that incorporated only 1 or 2 indices. The accuracy of weight estimation
      decreased at the extremes of BWs, leading to overestimation in low-BW categories
      as opposed to underestimation when the BW exceeded 4000 g. The precision of most
      models was lowest in the low-BW groups. CONCLUSIONS: To improve the accuracy of
      fetal weight estimation, sonographic models that are based on 3 or 4 fetal
      biometric indices should be preferred. Recognizing the accuracy and the tendency
      for underestimation or overestimation of each of the available models is
      important for the judicious interpretation of fetal weight estimations,
      especially at the extremes of fetal weight.

PMID- 19389902
TI  - Are patients with twin-twin transfusion syndrome and a very short cervix
      candidates for laser surgery?
AB  - OBJECTIVES: The purpose of this study was to determine the relationship between
      cervical length (CL) and perinatal outcomes in cases of twin-twin transfusion
      syndrome (TTTS) treated with laser surgery and to assess whether patients with a
      very short cervix (0.5-1.9 cm) are appropriate candidates for laser surgery.
      METHODS: All women who underwent laser surgery for TTTS from March 2006 to April
      2008 at the study institution were evaluated consecutively. Patients were grouped
      according to pre-operative CL: greater than 2.5, 2 to 2.5, and 0.5 to 1.9 cm. The
      gestational age at delivery, latency from laser surgery to delivery, and 30-day
      neonatal survival were documented prospectively and compared among these groups.
      RESULTS: The 99 women in the study population were grouped by CL: greater than
      2.5 cm (n = 76), 2 to 2.5 cm (n = 13), and 0.5 to 1.9 cm (n = 10). For these
      groups, the median gestational ages at delivery were 34, 32.29, and 31.86 weeks,
      respectively (P = .411). The median latencies from laser surgery to delivery were
      12.79, 11, and 11.07 weeks (P = .424). The frequency rates of at least 1
      surviving twin were 69 of 76 (91%), 13 of 13 (100%), and 8 of 10 (80%) (P =
      .254). Finally, dual survivors were observed in 54 of 76 (71%), 12 of 13 (92%),
      and 5 of 10 (50%) (P = .08). CONCLUSIONS: In cases of TTTS complicated by a very
      short cervix (0.5-1.9 cm), treatment with laser surgery resulted in perinatal
      outcomes that were sufficiently favorable to justify the surgery, suggesting that
      these patients should not be excluded from undergoing laser surgery for TTTS.

PMID- 19389903
TI  - Doppler sonographic criteria for the diagnosis of inferior mesenteric artery
      stenosis.
AB  - OBJECTIVE: The purpose of this study was to define the optimal Doppler criteria
      for the diagnosis of inferior mesenteric artery (IMA) stenosis in patients with
      suspected chronic mesenteric ischemia (CMI). METHODS: A retrospective review of
      205 dedicated color and pulsed Doppler sonographic studies of mesenteric arteries
      was performed in 205 patients. All studies were performed in patients with
      suspected CMI. Correlative angiography was available in 50 patients. RESULTS: The
      IMA was visualized in 176 of 205 Doppler sonographic examinations (86%) and in
      92% of the correlative studies. The visualization rate for the detection of a
      patent IMA by Doppler sonography in this series was 90%. The ranges of the peak
      systolic velocity (PSV), end-diastolic velocity (EDV), and mesenteric-aortic
      velocity ratio (MAR) in the nonstenotic IMA were 70 to 200 cm/s, 0 to 33 cm/s,
      and 0.7 to 3.7, respectively. The ranges of the PSV, EDV, and MAR in IMA stenosis
      were 200 to 485 cm/s, 0 to 177 cm/s, and 0.69 to 8.1. The threshold values for
      severe IMA stenosis by logistic regression analysis (n = 42) were as follows:
      PSV, greater than 200 cm/s; EDV, greater than 25 cm/s; and MAR, greater than 2.5,
      with sensitivities of 90%, 40%, and 80%; specificities of 97%, 91%, and 88%;
      positive predictive values (PPVs) of 90%, 57%, and 67%; negative predictive
      values (NPVs) of 97%, 83%, and 93%; and accuracy of 95%, 79%, and 86%,
      respectively. CONCLUSIONS: We found that a PSV of greater than 200 cm/s was the
      best criterion for the diagnosis of IMA stenosis. The sensitivity, specificity,
      PPV, NPV, and accuracy for the PSV were 90%, 97%, 90%, 97%, and 95%,
      respectively.

PMID- 19389904
TI  - Peripherally inserted central catheter placement with the sonic flashlight:
      initial clinical trial by nurses.
AB  - OBJECTIVE: We describe a case series constituting the first clinical trial by
      intravenous (IV) team nurses using the sonic flashlight (SF) for ultrasound
      guidance of peripherally inserted central catheter (PICC) placement. METHODS: Two
      IV team nurses with more than 10 years of experience with placing PICCs and 3 to
      6 years of experience with ultrasound attempted to place PICCs under ultrasound
      guidance in patients requiring long-term IV access. One of two methods of
      ultrasound guidance was used: conventional ultrasound (CUS; 60 patients) or a new
      device called the SF (44 patients). The number of needle punctures required to
      gain IV access was recorded for each patient. RESULTS: In both methods, 87% of
      the cases resulted in successful venous access on the first attempt. The average
      number of needle sticks per patient was 1.18 for SF-guided procedures compared
      with 1.20 for CUS-guided procedures. No significant difference was found in the
      distribution of the number of attempts between the two methods. Anecdotal
      comments by the nurses indicated the comparative ease of use of the SF display,
      although the relatively small scale of the SF image compared with the CUS image
      was also noted. CONCLUSIONS: We have shown that the SF is a safe and effective
      device for guidance of PICC placement in the hands of experienced IV team nurses.
      The advantage of placing the ultrasound image at its actual location must be
      balanced against the relatively small scale of the SF image.

PMID- 19389905
TI  - Isolated torsion of the fallopian tube: the sonographic whirlpool sign.
AB  - OBJECTIVE: The purpose of this series is to describe the sonographic features of
      isolated torsion of the fallopian tube. METHODS: Sonography was performed in 4
      women with acute lower abdominal pain. RESULTS: The uterus and ovaries were
      normal in the 4 women. The ipsilateral fallopian tube was distended with fluid. A
      round mass was seen close to the tube. A sonographic whirlpool sign was seen on
      rocking movement of the probe over the mass. Ipsilateral torsion of the fallopian
      tube was confirmed at surgery in all of them. CONCLUSION: The sonographic
      whirlpool sign is the specific sign of tubal torsion.

PMID- 19389906
TI  - Prenatal diagnosis of spontaneous septostomy of the dividing membranes in
      complicated monochorionic diamniotic multiple gestations.
AB  - OBJECTIVE: The purpose of this series is to describe the prenatal diagnostic and
      management challenges of spontaneous septostomy of the dividing membrane (SSDM)
      in complicated monochorionic diamniotic (MoDi) pregnancies. METHODS: A
      retrospective review of all MoDi multiple gestations referred for fetal therapy
      was conducted. Spontaneous septostomy of the dividing membrane was suspected if a
      prior invasive procedure had not been performed and the following sonographic
      hallmarks were identified: twins occupying the same side of the dividing
      membrane, twin-twin transfusion syndrome (TTTS) with polyhydramnios in the
      donor's sac despite a collapsed donor bladder, and umbilical cord entanglement.
      Spontaneous septostomy of the dividing membrane was confirmed in all cases at the
      time of surgical fetoscopy, which was performed to treat an underlying condition
      of TTTS, selective intrauterine growth restriction (SIUGR), or the twin reversed
      arterial perfusion (TRAP) sequence. RESULTS: Of 217 complicated MoDi multiple
      gestations without prior invasive procedures referred for possible fetal therapy,
      4 (1.8%) were identified with SSDM. The mean (range) gestational age at diagnosis
      was 19.7 (18-20.9) weeks. Two cases were diagnosed with TTTS complicated by SSDM
      after both fetuses were identified on the same side of the dividing membranes (1
      case) or polyhydramnios was noted in the donor's sac despite a collapsed donor
      bladder (1 case). Both cases had substantial preoperative fetal deterioration
      because of a delay in diagnosis and treatment of TTTS. The remaining 2 SSDM
      cases, 1 with SIUGR and 1 with the TRAP sequence, were diagnosed after umbilical
      cord entanglement was recognized. CONCLUSIONS: Spontaneous septostomy of the
      dividing membrane in MoDi gestations is a rare condition that poses diagnostic
      and management challenges.

PMID- 19389907
TI  - Prenatal sonographic diagnosis of Rubinstein-Taybi syndrome.

PMID- 19389908
TI  - Prenatal diagnosis of double aneuploidy, 48,XXY,+21, and review of the
      literature.

PMID- 19389909
TI  - Prenatal diagnosis of a cavum veli interpositi.

PMID- 19389910
TI  - Diagnostic and prognostic aspects in the sonographic evaluation of a fetus with
      an oral mass.

PMID- 19389911
TI  - Color Doppler sonographic features of a Krukenberg tumor in pregnancy.

PMID- 19389912
TI  - Sonographic and multiplanar computed tomographic findings of large uterine
      perforation 2 weeks after first-trimester pregnancy termination.

PMID- 19389913
TI  - Type 1 congenital extrahepatic portosystemic shunt.

PMID- 19389914
TI  - Differential roles of the fan-shaped body and the ellipsoid body in Drosophila
      visual pattern memory.
AB  - The central complex is a prominent structure in the Drosophila brain. Visual
      learning experiments in the flight simulator, with flies with genetically altered
      brains, revealed that two groups of horizontal neurons in one of its
      substructures, the fan-shaped body, were required for Drosophila visual pattern
      memory. However, little is known about the role of other components of the
      central complex for visual pattern memory. Here we show that a small set of
      neurons in the ellipsoid body, which is another substructure of the central
      complex and connected to the fan-shaped body, is also required for visual pattern
      memory. Localized expression of rutabaga adenylyl cyclase in either the fan
      shaped body or the ellipsoid body is sufficient to rescue the memory defect of
      the rut(2080) mutant. We then performed RNA interference of rutabaga in either
      structure and found that they both were required for visual pattern memory.
      Additionally, we tested the above rescued flies under several visual pattern
      parameters, such as size, contour orientation, and vertical compactness, and
      revealed differential roles of the fan-shaped body and the ellipsoid body for
      visual pattern memory. Our study defines a complex neural circuit in the central
      complex for Drosophila visual pattern memory.

PMID- 19389915
TI  - Cocaine self-administration alters the relative effectiveness of multiple memory
      systems during extinction.
AB  - Rats were trained to run a straight-alley maze for an oral cocaine or sucrose
      vehicle solution reward, followed by either response or latent extinction
      training procedures that engage neuroanatomically dissociable "habit" and
      "cognitive" memory systems, respectively. In the response extinction condition,
      rats performed a runway approach response to an empty fluid well. In the latent
      extinction condition, rats were placed at the empty fluid well without performing
      a runway approach response. Rats trained with the sucrose solution displayed
      normal extinction behavior in both conditions. In contrast, rats trained with the
      cocaine solution showed normal response extinction but impaired latent
      extinction. The selective impairment of latent extinction indicates that oral
      cocaine self-administration alters the relative effectiveness of multiple memory
      systems during subsequent extinction training.

PMID- 19389916
TI  - Xylosyltransferase II is a significant contributor of circulating
      xylosyltransferase levels and platelets constitute an important source of
      xylosyltransferase in serum.
AB  - Circulating glycosyltransferases including xylosyltransferases I (XylT1) and II
      (XylT2) are potential serum biomarkers for various diseases. Understanding what
      influences the serum activity of these enzymes as well as the sources of these
      enzymes is important to interpreting the significance of alterations in enzyme
      activity during disease. This article demonstrates that in the mouse and human
      the predominant XylT in serum is XylT2. Furthermore, that total XylT levels in
      human serum are approximately 200% higher than those in plasma due in part to
      XylT released by platelets during blood clotting in vitro. In addition, the data
      from Xylt2 knock-out mice and mice with liver neoplasia show that liver is a
      significant source of serum XylT2 activity. The data presented suggest that serum
      XylT levels may be an informative biomarker in patients who suffer from diseases
      affecting platelet and/or liver homeostasis.

PMID- 19389917
TI  - Transglycosylation-based fluorescent labeling of 6-gala series glycolipids by
      endogalactosylceramidase.
AB  - Although 6-gala series glycosphingolipids possessing R-Gal (alpha/beta) 1-6Gal
      beta 1-1'Cer have been found in some mollusks, pathogenic parasites, and fungi,
      their physiological functions and metabolic pathway are not fully understood. We
      described a novel method of detecting 6-gala series glyco- sphingolipids
      utilizing the specificity of endogalactosylceramidase (EGALC), which is capable
      of hydrolyzing 6-gala series glycosphingolipids to produce intact
      oligosaccharides and ceramides. EGALC catalyzes not only hydrolysis but also a
      transglycosylation reaction. In the latter reaction, EGALC transfers
      oligosaccharides from the glycosphingolipids to acceptors such as fluorescent 1
      alkanols. Based on the transglycosylation reaction of EGALC, a specific, easy,
      fast, sensitive, and reproducible method of detecting 6-gala series
      glycosphingolipids was developed using NBD-pentanol as an acceptor. The
      fluorescent products, NBD-pentanol-conjugated 6-gala oligosaccharides, were
      separated and detected by TLC or HPLC with a fluorescent detector. Moreover, it
      was revealed that as well as glycosphingolipids, a glycoglycerolipid,
      digalactosyldiacylglycerol, was utilized by EGALC as a donor substrate. This
      method was successfully applied to detect 6-gala series glycosphingolipids in a
      fungus, Rhizopus oryzae, and a parasite, Taenia crassiceps. The method would be
      useful for studying glycosphingolipids and galactosyl glycerolipids which share
      the Gal (alpha/beta) 1-6Gal structure.

PMID- 19389918
TI  - Regulated expression of the HNK-1 carbohydrate is essential for medaka (Oryzias
      latipes) embryogenesis.
AB  - Carbohydrates are known to play essential roles in various biological processes
      including development. However, it remains largely unknown which carbohydrate
      structure takes part in each biological event. Here, we examined the roles of the
      human natural killer-1 (HNK-1) carbohydrate in medaka embryogenesis. We first
      cloned two medaka glucuronyltransferases, GlcAT-P and GlcAT-S, key enzymes for
      HNK-1 biosynthesis. Overexpression of these glucuronyltransferases affected
      morphogenetic processes. In addition, loss-of-function experiments revealed that
      GlcAT-P is physiologically indispensable for head morphogenesis and GlcAT-P
      depletion also led to markedly increased apoptosis. However, even when the
      apoptosis was blocked, abnormal head morphogenesis caused by GlcAT-P depletion
      was still observed, indicating that apoptosis was not the main cause of the
      abnormality. Moreover, in situ hybridization analyses indicated that GlcAT-P
      depletion resulted in the abnormal formation of the nervous system but not in
      cell specification. These results suggest that tight regulation of HNK-1
      expression is essential for proper morphogenesis of medaka embryos.

PMID- 19389919
TI  - Trace amine-associated receptors as emerging therapeutic targets.
AB  - Endogenous trace amines (TAs) of unknown biological function are structurally
      related to classic monoaminergic neurotransmitters and found at low
      concentrations in the mammalian brain. Their recently discovered group of G
      protein-coupled receptors, trace amine-associated receptors (TAARs), may
      represent putative targets not only for trace and other amines but also for a
      variety of monoaminergic compounds, including amphetamines and monoamine
      metabolites. The trace amine-associated receptor 1 (TAAR1), which is in part
      associated with the monoaminergic neuronal circuitry controlling various
      functions, including movement, is the best characterized of the class, although
      little is known about its regulation and function. Here we review the
      pharmacology and biochemical properties of the TAAR1 and its physiological
      functions as revealed in studies involving knockout mice lacking this receptor.
      Potential therapeutic applications of future selective TAAR1 agonists and
      antagonists are also discussed. Although understanding of biology and functions
      mediated by other TAARs is still in its infancy, it is expected that further
      characterization of the functional roles and biochemical properties of TAARs and
      identification of endogenous and exogenous ligands will eventually promote these
      receptors as an attractive class of targets to correct monoaminergic processes
      that could be dysfunctional in a host of disorders of brain and periphery.

PMID- 19389920
TI  - Inactivation and biotransformation of the endogenous cannabinoids anandamide and
      2-arachidonoylglycerol.
AB  - The cannabinoid field is currently an active research area. Anandamide (AEA) and
      2-arachidonoylglycerol (2-AG) are the most characterized endogenous cannabinoids
      (also known as endocannabinoids). These neuromodulators have been implicated in
      various physiologically relevant phenomena, including mood (Witkin et al., 2005),
      the immune response (Ashton, 2007), appetite (Kirkham and Tucci, 2006),
      reproduction (Wang et al., 2006), spasticity (Pertwee, 2002), and pain (Hohmann
      and Suplita, 2006). Pharmacological manipulation of AEA and 2-AG signaling should
      prove to have significant therapeutic applications in disorders linked to
      endocannabinoid signaling. One way to alter endocannabinoid signaling is to
      regulate the events responsible for termination of the endocannabinoid signal
      cellular uptake and metabolism. However, to pharmacologically exploit AEA and/or
      2-AG signaling in this way, we must first gain a better understanding of the
      proteins and mechanisms governing these processes. This review serves as an
      introduction to the endocannabinoid system with an emphasis on the proteins and
      events responsible for the termination of AEA and 2-AG signaling.

PMID- 19389921
TI  - Site specificity of agonist and second messenger-activated kinases for
      somatostatin receptor subtype 2A (Sst2A) phosphorylation.
AB  - Somatostatin receptor subtype 2A (sst2A) mediates many of the endocrine and
      neuronal actions of somatostatin and is the target of somatostatin analogs in
      cancer therapy. As with many G-protein-coupled receptors, agonist stimulation
      causes sst2A receptor desensitization and internalization, events that require
      receptor phosphorylation. Furthermore, heterologous receptor activation of
      protein kinase C (PKC) also increases sst2A receptor phosphorylation and
      internalization. Here we analyzed a series of sst2A receptor mutants
      biochemically to identify residues in the receptor carboxyl terminus that were
      phosphorylated upon agonist stimulation, and we then generated four
      phosphorylation-sensitive antibodies to those residues. Once the selectivity of
      each antibody for its phosphorylated and nonphosphorylated target sequence was
      determined, the phospho-site-specific antibodies were used to demonstrate that
      somatostatin treatment of Chinese hamster ovary (CHO) cells expressing the wild
      type sst2A receptor increased phosphorylation on five residues in the receptor C
      terminus: Ser341, Ser343, Ser348, Thr353, and Thr354. Phorbol 12-myristate 13
      acetate (PMA) increased receptor phosphorylation only on Ser343. Inhibition of
      PKC blocked PMA but not somatostatin stimulation, showing that different kinases
      catalyzed Ser343 phosphorylation. In contrast, somatostatin-stimulated sst2A
      receptor phosphorylation was inhibited by knockdown of G-protein coupled receptor
      kinase-2 with siRNA. Somatostatin increased sst2A receptor phosphorylation on the
      same five residues in GH4C1 pituitary cells as in CHO cells. However, PMA
      stimulated sst2A receptor phosphorylation on both Ser343 and Ser348 in GH4C1
      cells. These results characterize the complex pattern of sst2A receptor
      phosphorylation by agonist and second messenger-activated kinases for the first
      time and indicate that cell type-specific regulation of sst2A receptor
      phosphorylation occurs.

PMID- 19389922
TI  - In vivo and in vitro structure-activity relationships and structural conformation
      of Kisspeptin-10-related peptides.
AB  - Kisspeptins, the natural ligands of the G protein-coupled receptor KISS1R,
      comprise a family of related peptides derived from the proteolytic processing of
      a common precursor encoded by the KISS1 gene. Among those, Kisspeptin-10 (Kp-10)
      contains the basic residues to retain full functional activity and exhibits
      higher receptor affinity and biopotency than longer forms of the peptide.
      Although kisspeptins were first characterized by their ability to inhibit tumor
      metastasis, recent studies have revealed that the KISS1/KISS1R system plays an
      essential role in the neuroendocrine control of the reproductive axis. In this
      context, development and functional analysis of Kp-10 analogs may help in the
      search for new agonists and antagonists as valuable tools to manipulate the
      KISS1/KISS1R system and hence fertility. We report herein functional and
      structural analyses of a series of Ala-substituted rat kp-10 analogs, involving
      [Ca(2+)](i) responses in rat kiss1r-transfected Chinese hamster ovary cells,
      dynamic luteinizing hormone (LH) responses in vivo, and NMR structural studies.
      In vitro assays revealed that Ala substitutions in positions 6 or 10 of kp-10
      resulted in a significant increase in EC(50) values (>6.46 x 10(-6) M versus 1.54
      to 2.6 x 10(-8) M for rat and human Kp-10, respectively) and a substantial
      decrease in the proportion of responsive cells coupled to a marked increase in
      the time required to reach maximal response. In vivo assays showed that Ala(6)
      substitution diminished and Ala(10) substitution eliminated LH secretory
      responses, whereas coadministration of each analog failed to affect the LH
      releasing ability of kp-10. Molecular modeling under NMR restraints revealed that
      kp-10 exhibits a helicoidal structure between the Asn(4) and Tyr(10) residues,
      with mixed alpha- and 3(10)-helix characteristics. Ala(6) substitution induced
      limited destabilization of the helix around the position of the substitution.
      Ala(10) substitution was found to totally disrupt the helical structure in the C
      terminal region of the molecule. Taken together, our results indicate that
      positions 6 and 10 are critical for kp-10 action at kiss1r and suggest that
      modifications in these positions could lead to the generation of new kisspeptin
      agonists and/or antagonists with altered functional and perhaps binding
      properties. Furthermore, they emphasize the importance of using combined,
      multidisciplinary approaches, including in vivo studies, to reliably evaluate
      structure function properties of novel kisspeptin analogs.

PMID- 19389923
TI  - In vitro pharmacological characterization of a novel allosteric modulator of
      alpha 7 neuronal acetylcholine receptor, 4-(5-(4-chlorophenyl)-2-methyl-3
      propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744), exhibiting unique
      pharmacological profile.
AB  - Targeting alpha7 neuronal acetylcholine receptors (nAChRs) with selective
      agonists and positive allosteric modulators (PAMs) is considered a therapeutic
      approach for managing cognitive deficits in schizophrenia and Alzheimer's
      disease. In this study, we describe a novel type II alpha7 PAM, 4-(5-(4
      chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744),
      that exhibits a unique pharmacological profile. In oocytes expressing alpha7
      nAChRs, A-867744 potentiated acetylcholine (ACh)-evoked currents, with an EC(50)
      value of approximately 1 microM. At highest concentrations of A-867744 tested,
      ACh-evoked currents were essentially nondecaying. At lower concentrations, no
      evidence of a distinct secondary component was evident in contrast to 4
      naphthalen-1-yl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonic acid
      amide (TQS), another type II alpha7 PAM. In the presence of A-867744, ACh
      concentration responses were potentiated by increases in potency, Hill slope, and
      maximal efficacy. When examined in rat hippocampus CA1 stratum radiatum
      interneurons or dentate gyrus granule cells, A-867744 (10 microM) increased
      choline-evoked alpha7 currents and recovery from inhibition/desensitization, and
      enhanced spontaneous inhibitory postsynaptic current activity. A-867744, like
      other alpha7 PAMs tested [1-(5-chloro-2-hydroxyphenyl)-3-(2-chloro-5
      trifluoromethyl-phenyl)urea (NS1738), TQS, and 1-(5-chloro-2,4-dimethoxy-phenyl)
      3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596)], did not displace the binding of
      [(3)H]methyllycaconitine to rat cortex alpha7(*) nAChRs. However, unlike these
      PAMs, A-867744 displaced the binding of the agonist [(3)H](1S,4S)-2,2-dimethyl-5
      (6-phenylpyridazin-3-yl)-5-aza-2-azoniabicyclo[2.2.1]heptane (A-585539) in rat
      cortex, with a K(i) value of 23 nM. A-867744 neither increased agonist-evoked
      responses nor displaced the binding of [(3)H]A-585539 in an alpha7/5
      hydroxytryptamine(3) (alpha7/5-HT(3)) chimera, suggesting an interaction distinct
      from the alpha7 N terminus or M2-3 loop. In addition, A-867744 failed to
      potentiate responses mediated by 5-HT(3A) or alpha3beta4 and alpha4beta2 nAChRs.
      In summary, this study identifies a novel and selective alpha7 PAM showing
      activity at recombinant and native alpha7 nAChRs exhibiting a unique
      pharmacological interaction with the receptor.

PMID- 19389924
TI  - The neuroactive peptide N-acetylaspartylglutamate is not an agonist at the
      metabotropic glutamate receptor subtype 3 of metabotropic glutamate receptor.
AB  - The peptide N-acetylaspartylglutamate (NAAG) is present in high concentrations in
      the mammalian central nervous system. Various mechanisms have been proposed for
      its action, including selective activation of the metabotropic glutamate receptor
      (mGluR) subtype 3, its action at the N-methyl-D-aspartate receptor, or the
      production of glutamate by its hydrolysis catalyzed by an extracellular protease.
      To re-examine its agonist activity at mGluR3, we coexpressed human or rat mGluR3
      with G protein inward rectifying channels in Xenopus laevis oocytes. High
      performance liquid chromatography analysis of commercial sources of NAAG showed
      0.38 to 0.48% glutamate contamination. Although both human and rat mGluR3 were
      highly sensitive to glutamate, with EC(50) values of 58 and 28 nM, respectively,
      purified NAAG (100 microM) had little activity (7.7% of full activation by
      glutamate). Only in the millimolar range did it show significant activity,
      possibly due to residual traces of glutamate remaining in the purified NAAG
      preparations. In contrast, the unpurified NAAG sample did produce a full agonist
      response with mGluR3 coexpressed with G alpha(15), with an EC(50) of 120 microM,
      as measured by a calcium release assay. This response can be explained by the
      0.38 to 0.48% glutamate contamination. Our results suggest that NAAG may not have
      a direct agonist activity at the mGluR3 receptor. Thus, several in vivo and in
      vitro published results that did not address the issue of glutamate contamination
      of NAAG preparations may need to be re-evaluated.

PMID- 19389925
TI  - Alternative proteolytic processing of hepatocyte growth factor during wound
      repair.
AB  - Wound healing is a crucial regenerative process in all organisms. We examined
      expression, integrity, and function of the proteins in the hepatocyte growth
      factor (HGF)/c-Met signaling pathway in normally healing and non-healing human
      skin wounds. Whereas in normally healing wounds phosphorylation of c-Met was most
      prominent in keratinocytes and dermal cells, in non-healing wounds
      phosphorylation of c-Met was barely detectable, suggesting reduced c-Met
      activation. In wound exudates obtained from non-healing, but not from healing
      wounds, HGF protein was a target of substantial proteolytic processing that was
      different from the classical activation by known serine proteases. Western blot
      analysis and protease inhibitor studies revealed that HGF is a target of
      neutrophil elastase and plasma kallikrein during skin repair. Proteolytic
      processing of HGF by each of these proteases significantly attenuated
      keratinocyte proliferation, wound closure capacity in vitro, and c-Met signal
      transduction. Our findings reveal a novel pathway of HGF processing during skin
      repair. Conditions in which proteases are imbalanced and tend toward increased
      proteolytic activity, as in chronic non-healing wounds, might therefore
      compromise HGF activity due to the inactivation of the HGF protein and/or the
      generation of HGF fragments that ultimately mediate a dominant negative effect
      and limit c-Met activation.

PMID- 19389926
TI  - Requirement of the Akt/beta-catenin pathway for uterine carcinosarcoma genesis,
      modulating E-cadherin expression through the transactivation of slug.
AB  - Uterine carcinosarcomas (UCSs) are considered to represent true examples of the
      epithelial-mesenchymal transition. Akt plays a key role in the induction of
      epithelial-mesenchymal transition, but little is known about its involvement in
      tumorigenesis. Here we examined the functional roles of the Akt/beta-catenin
      pathway in UCSs. In clinical samples, phospho-Akt (pAkt) expression was found to
      be significantly increased in mesenchymal compared with epithelial components,
      exhibiting both positive and negative correlations with nuclear beta-catenin and
      E-cadherin, respectively. Expression levels of the transcription factor Slug were
      also significantly up-regulated in the mesenchymal components and strongly
      correlated with both pAkt and nuclear beta-catenin. In endometrial cancer cell
      lines, active Akt induced the stabilization of nuclear beta-catenin through the
      phosphorylation of GSK-3beta, and this, in turn, led to the transactivation of
      Slug, which was mediated by nuclear beta-catenin. Moreover, Slug overexpression
      itself caused repression of E-cadherin, with subtle changes in cell morphology.
      In addition, knockdown of the retinoblastoma gene product (Rb) up-regulated pAkt
      and repressed E-cadherin, consistent with the in vivo finding of significantly
      decreased Rb expression in mesenchymal components. These findings suggest that
      changes in the Akt/beta-catenin pathway, as well as alterations in Rb expression,
      may be essential for both the establishment and maintenance of phenotypic
      characteristics of UCSs, playing key roles in the regulation of E-cadherin
      through the transactivation of the Slug gene.

PMID- 19389927
TI  - Osteoprotegerin abrogated cortical porosity and bone marrow fibrosis in a mouse
      model of constitutive activation of the PTH/PTHrP receptor.
AB  - Intracortical porosities and marrow fibrosis are hallmarks of hyperparathyroidism
      and are present in bones of transgenic mice expressing constitutively active
      parathyroid hormone/parathyroid hormone-related protein receptors (PPR*Tg).
      Cortical porosity is the result of osteoclast activity; however, the etiology of
      marrow fibrosis is poorly understood. While osteoclast numbers and activity are
      regulated by osteoprotegerin (OPG), bisphosphonates suppress osteoclast activity
      but not osteoclast numbers. We therefore used OPG and bisphosphonates to evaluate
      the extent to which osteoclasts, as opposed to bone resorption, regulate marrow
      fibrosis in PPR*Tg mice after treatment of animals with vehicle, OPG,
      alendronate, or zoledronate. All three agents similarly increased trabecular bone
      volume in both PPR*Tg and control mice, suggesting that trabecular bone
      resorption was comparably suppressed by these agents. However, the number of
      trabecular osteoclasts was greatly decreased by OPG but not by either alendronate
      or zoledronate. Furthermore, intracortical porosity and marrow fibrosis were
      virtually abolished by OPG treatment, whereas alendronate and zoledronate only
      partially reduced these two parameters. The greater reductions in cortical
      porosity and increments in cortical bone mineral density with OPG in PPR*Tg mice
      were associated with greater improvements in bone strength. The differential
      effect of OPG versus bisphosphonates on marrow fibrosis, despite similar effects
      on trabecular bone volume, suggests that marrow fibrosis was related not only to
      bone resorption but also to the presence of osteoclasts.

PMID- 19389928
TI  - Monokine induced by interferon-gamma (MIG/CXCL9) is derived from both donor and
      recipient sources during rejection of class II major histocompatibility complex
      disparate skin allografts.
AB  - Chemokines, including monokine induced by interferon-gamma (Mig/CXCL9), are
      produced both in allografts and during the direct T-cell infiltration that
      mediates graft rejection. Neither the specific production nor contribution of
      allograft donor versus recipient Mig in allograft rejection is currently known.
      C57BL/6 mice with a targeted deletion in the Mig gene were used as both skin
      allograft donors and recipients in a class II major histocompatibility complex
      mismatched graft model to test the requirement for donor- versus recipient
      derived Mig for acute rejection. B6.Mig(-/-) allografts had a 10-day prolonged
      survival in B6.H-2(bm12) recipients when compared with wild-type C57BL/6
      allograft donors, and B6.H-2(bm12) skin allografts had a 5-day prolonged survival
      in B6.Mig(-/-) versus wild-type recipients. Transplantation of B6.Mig(-/-) skin
      grafts onto B6.H-2(bm12).Mig(-/-) recipients resulted in further prolonged
      allograft survival with more than 30% of the grafts surviving longer than 60
      days. Prolonged allograft survival was also associated with delayed cellular
      infiltration into grafts but not with altered T-cell proliferative responses to
      donor stimulators. Immunohistochemical staining of allograft sections indicated
      that Mig is produced by both donor- and recipient-derived sources, but Mig from
      each of these sources appeared in different areas of the allograft tissue. These
      results therefore demonstrate the synergy of donor- and recipient-derived Mig in
      promoting T-cell infiltration into allografts.

PMID- 19389929
TI  - Loss of matriptase suppression underlies spint1 mutation-associated ichthyosis
      and postnatal lethality.
AB  - Hepatocyte growth factor activator inhibitor-1 (HAI)-1 is an epithelial Kunitz
      type transmembrane serine protease inhibitor that is encoded by the SPINT1 gene.
      HAI-1 displays potent inhibitory activity toward a large number of trypsin-like
      serine proteases. HAI-1 was recently shown to play an essential role in postnatal
      epithelial homeostasis. Thus, Spint1-deficient mice were found to display severe
      growth retardation and are unable to survive beyond postnatal day 16. The mice
      present histologically with overt hyperkeratosis of the forestomach,
      hyperkeratosis and acanthosis of the epidermis, and hypotrichosis associated with
      abnormal cuticle development. In this study, we show that loss of inhibition of a
      proteolytic pathway that is dependent on the type II transmembrane serine
      protease, matriptase, underlies the detrimental effects of postnatal Spint1
      deficiency. Matriptase and HAI-1 precisely co-localize in all tissues that are
      affected by the Spint1 disruption. Spint1-deficient mice that have low matriptase
      levels, caused by a hypomorphic mutation in the St14 gene that encodes
      matriptase, not only survived the neonatal period but were healthy and displayed
      normal long-term survival. Furthermore, a detailed histological analysis of
      neonatal, young adult, as well as aged mice did not reveal any abnormalities in
      Spint1-deficent mice that have low matriptase levels. This study identifies
      matriptase suppression as an essential function of HAI-1 in postnatal tissue
      homeostasis.

PMID- 19389930
TI  - Disruption of interleukin-1 signaling improves the quality of wound healing.
AB  - In this study, we investigated the role of interleukin (IL)-1 signaling in wound
      healing. IL-1 receptor type I (IL-1R) knockout (KO) mice showed reduced fibrosis
      in both cutaneous and deep tissue wounds, which was accompanied by a reduction in
      inflammatory cellular infiltration in cutaneous but not in deep tissue wounds.
      There were no differences in either total collagenolytic activity or in the
      expression of selected matrix metalloproteinases or tissue inhibitors of
      metalloproteinases between the wound fluids from wild-type or IL-1R KO mice.
      However, wound fluids from IL-1R KO mice contained lower levels of IL-6 compared
      with wild-type controls. In addition, the infusion of IL-6 into wounds in IL-1R
      KO mice did not increase fibrosis. Skin wounds in IL-1R KO animals had lower
      levels of collagen and improved restoration of normal skin architecture compared
      with skin wounds in wild-type mice. However, neither the tensile strength of
      incisional skin wounds nor the rate of closure of excisional wounds differed
      between IL-1R KO and wild-type animals. The reduced fibrotic response in wounds
      from IL-1R KO mice could be reproduced by the administration of an IL-1R
      antagonist. These findings suggest that pharmacological interference with IL-1
      signaling could have therapeutic value in the prevention of hypertrophic scarring
      and in the treatment of fibrotic diseases.

PMID- 19389931
TI  - Establishment of experimental eosinophilic vasculitis by IgE-mediated cutaneous
      reverse passive arthus reaction.
AB  - Prominent eosinophil infiltration is a characteristic of some forms of
      vasculitis, such as Churg-Strauss syndrome, also known as allergic granulomatous
      vasculitis. In the current study, we established a mouse model of cutaneous
      eosinophilic vasculitis by the cutaneous reverse passive Arthus reaction using
      IgE injection instead of IgG. Wild-type C57BL/6 mice were injected with IgE anti
      trinitrophenyl antibodies, followed immediately by intravenous administration of
      trinitrophenyl bovine serum albumin. IgE-mediated immune complex challenge
      induced substantial hemorrhage with marked infiltration of eosinophils in which
      neutrophils, mast cells, and macrophages were also mixed. This finding contrasted
      remarkably with the neutrophil-dominant infiltration pattern in IgG-mediated
      immune complex challenge. In the lesion, the expression level of monocyte
      chemotactic protein-3 was increased, and anti-monocyte chemotactic protein-3
      treatment resulted in a significant but incomplete blockade of eosinophil
      recruitment. Furthermore, mice lacking E-selectin, P-selectin, L-selectin, or
      intercellular adhesion molecule-1, as well as wild-type mice that received anti
      vascular cell adhesion molecule-1-blocking antibodies were assessed for the IgE
      mediated Arthus reaction. After 24 hours, the loss of P-selectin resulted in a
      significant reduction in eosinophil accumulation compared with both wild-type
      mice and other mouse mutants. Collectively, the Fc class of immunoglobulins,
      which forms these immune complexes, critically determines the disease
      manifestation of vasculitis. The IgE-mediated cutaneous reverse passive Arthus
      reaction may serve as an experimental model for cutaneous eosinophilic
      infiltration in vasculitis as well as in other diseases.

PMID- 19389933
TI  - Synthetic retinoid AM80 inhibits Th17 cells and ameliorates experimental
      autoimmune encephalomyelitis.
AB  - Recent evidence suggests that interleukin-17-producing CD4(+) T cells (Th17
      cells) are the dominant pathogenic cellular component in autoimmune inflammatory
      diseases, including multiple sclerosis. It has recently been demonstrated that
      all-trans retinoic acid can suppress Th17 differentiation and promote the
      generation of Foxp3(+) regulatory T cells via retinoic acid receptor signals.
      Here, we investigated the effects of AM80, a synthetic retinoid with enhanced
      biological properties to all-trans retinoic acid, on Th17 differentiation and
      function and evaluated its therapeutic potential in experimental autoimmune
      encephalomyelitis (EAE), an animal model of multiple sclerosis. AM80 treatment
      was more effective than all-trans retinoic acid in inhibiting Th17
      differentiation in vitro. Oral administration of AM80 was protective for the
      early development of EAE and the down-modulation of Th17 differentiation and
      effector functions in vivo. Moreover, AM80 inhibited interleukin-17 production by
      splenic memory T cells, in vitro-differentiated Th17 cells, and central nervous
      system-infiltrating effector T cells. Accordingly, AM80 was effective when
      administered therapeutically after the onset of EAE. Continuous AM80 treatment,
      however, was ineffective at inhibiting late EAE symptoms despite the maintained
      suppression of RORgammat and interleukin-17 expression levels by central nervous
      system-infiltrating T cells. We reveal that continuous AM80 treatment also led to
      the suppression of interleukin-10 production by a distinct T cell subset that
      expressed both Foxp3 and RORgammat. These findings suggest that retinoid
      signaling regulates both inflammatory Th17 cells and Th17-like regulatory cells.

PMID- 19389932
TI  - Protection of hippocampal neurogenesis from toll-like receptor 4-dependent innate
      immune activation by ablation of prostaglandin E2 receptor subtype EP1 or EP2.
AB  - Prostaglandin E2 is one of several eicosanoid products of the cyclooxygenase
      isozymes and is a key regulator of innate immune responses; it also possesses
      paracrine effects on mature neurons. The prostaglandin E2 receptor family
      consists of four subtypes of which EP1 and EP2 are known to be expressed by
      microglia. Lipopolysaccharide (LPS)-induced innate immune activation leads to the
      degeneration of intermediate progenitor cells (IPCs) that are destined for
      neuronal maturation in the hippocampal subgranular zone (SGZ); these cells can be
      identified by the expression of the transcription factor T-box brain gene 2
      (Tbr2). Importantly, depletion of LPS-induced IPCs from the SGZ is suppressed by
      cyclooxygenase inhibitors. We therefore tested the hypothesis that either EP1 or
      EP2 is critical to LPS-induced depletion of Tbr2+ IPCs from the SGZ. Expression
      of either EP1 or EP2 was necessary for Toll-like receptor 4-dependent innate
      immune-mediated depletion of these Tbr2+ IPCs in mice. Moreover, EP1 activation
      was directly toxic to murine adult hippocampal progenitor cells; EP2 was not
      expressed by these cells. Finally, EP1 modulated the response of murine primary
      microglia cultures to LPS but in a manner distinct from EP2. These results
      indicate that prostaglandin E2 signaling via either EP1 or EP2 is largely to
      completely necessary for Toll-like receptor 4-dependent depletion of IPCs from
      the SGZ and suggest further pharmacological strategies to protect this important
      neurogenic niche.

PMID- 19389934
TI  - The role of BRAF mutation and p53 inactivation during transformation of a
      subpopulation of primary human melanocytes.
AB  - Melanocytic nevi frequently harbor oncogenic BRAF mutations, but only a minority
      progress to melanoma. In human melanocytes, persistent BRAF(V600E) expression
      triggers oncogene-induced senescence, which implies that bypass of oncogene
      induced senescence is necessary for malignant transformation of melanocytes. We
      show that a subpopulation of primary human melanocytes with persistent expression
      of BRAF(V600E) do not enter oncogene-induced senescence, but instead survive
      despite heightened MAPK activity. Disruption of the p53 pathway using short
      hairpin RNA initiated rapid growth of these V600E(+) melanocytes in vitro. The
      resultant V600E(+)/p53(sh) melanocytes grew anchorage-independently in soft agar,
      formed pigmented lesions reminiscent of in situ melanoma in artificial skin
      reconstructs, and were weakly tumorigenic in vivo. Array comparative genomic
      hybridization analysis demonstrated that the transformed melanocytes acquired a
      substantial deletion in chromosome 13, which encodes the Rb1 tumor suppressor
      gene. Gene expression profiling study of nevi and melanomas showed that p53
      target genes were differentially expressed in melanomas compared with nevi,
      suggesting a dysfunctional p53 pathway in melanoma in vivo. In summary, these
      data demonstrate that a subpopulation of melanocytes possesses the ability to
      survive BRAF(V600E)-induced senescence, and suggest that p53 inactivation may
      promote malignant transformation of these cells.

PMID- 19389939
TI  - Editorial expression of concern.

PMID- 19389935
TI  - Activation of the endoplasmic reticulum stress-associated transcription factor x
      box-binding protein-1 occurs in a subset of normal germinal-center B cells and in
      aggressive B-cell lymphomas with prognostic implications.
AB  - X box-binding protein 1 (Xbp-1) is a transcription factor that is required for
      the terminal differentiation of B lymphocytes into plasma cells. The Xbp-1 gene
      is activated in response to endoplasmic reticulum stress signals, which generate
      a 50-kDa nuclear protein that acts as a potent transactivator and regulates the
      expression of genes related to the unfolded protein response. Activated Xbp-1 is
      essential for cell survival in plasma-cell tumors but its role in B-cell
      lymphomas is unknown. We analyzed the expression of activated Xbp-1 in reactive
      lymphoid tissues, 411 lymphomas and plasma-cell neoplasms, and 24 B-cell lines.
      In reactive tissues, Xbp-1 was only found in nuclear extracts. Nuclear expression
      of Xbp-1 was observed in occasional reactive plasma cells and in a subpopulation
      of Irf-4(+)/Bcl-6(-)/Pax-5(-) B cells in the light zones of reactive germinal
      centers, probably representing cells committed to plasma-cell differentiation.
      None of the low-grade lymphomas showed evidence of Xbp-1 activation; however, Xbp
      1 activation was found in 28% of diffuse large B-cell lymphomas, independent of
      germinal or postgerminal center phenotype, as well as in 48% of plasmablastic
      lymphomas and 69% of plasma-cell neoplasms. Diffuse large B-cell lymphomas with
      nuclear Xbp-1 expression had a significantly worse response to therapy and
      shorter overall survival compared with negative tumors. These findings suggest
      that Xbp-1 activation may play a role in the pathogenesis of aggressive B-cell
      lymphomas.

PMID- 19389940
TI  - Effect of solvent and temperature on the size distribution of casein micelles
      measured by dynamic light scattering.
AB  - The objectives of this study were to investigate the effect of the solvent on the
      accuracy of casein micelle particle size determination by dynamic light
      scattering (DLS) at different temperatures and to establish a clear protocol for
      these measurements. Dynamic light scattering analyses were performed at 6, 20,
      and 50 degrees C using a 90Plus Nanoparticle Size Analyzer (Brookhaven
      Instruments, Holtsville, NY). Raw and pasteurized skim milk were used as sources
      of casein micelles. Simulated milk ultrafiltrate, ultrafiltered water, and
      permeate obtained by ultrafiltration of skim milk using a 10-kDa cutoff membrane
      were used as solvents. The pH, ionic concentration, refractive index, and
      viscosity of all solvents were determined. The solvents were evaluated by DLS to
      ensure that they did not have a significant influence on the results of the
      particle size measurements. Experimental protocols were developed for accurate
      measurement of particle sizes in all solvents and experimental conditions. All
      measurements had good reproducibility, with coefficients of variation below 5%.
      Both the solvent and the temperature had a significant effect on the measured
      effective diameter of the casein micelles. When ultrafiltered permeate was used
      as a solvent, the particle size and polydispersity of casein micelles decreased
      as temperature increased. The effective diameter of casein micelles from raw skim
      milk diluted with ultrafiltered permeate was 176.4 +/- 5.3 nm at 6 degrees C,
      177.4 +/- 1.9 nm at 20 degrees C, and 137.3 +/- 2.7 nm at 50 degrees C. This
      trend was justified by the increased strength of hydrophobic bonds with
      increasing temperature. Overall, the results of this study suggest that the most
      suitable solvent for the DLS analyses of casein micelles was casein-depleted
      ultrafiltered permeate. Dilution with water led to micelle dissociation, which
      significantly affected the DLS measurements, especially at 6 and 20 degrees C.
      Simulated milk ultrafiltrate seemed to give accurate results only at 20 degrees
      C. Results obtained in simulated milk ultrafiltrate at 6 degrees C could not be
      explained based on the known effects of temperature on the casein micelle,
      whereas at 50 degrees C, precipitation of amorphous calcium phosphate affected
      the DLS measurement.

PMID- 19389941
TI  - Supercritical fluid fractionation of fatty acid ethyl esters from butteroil.
AB  - Countercurrent supercritical fractionation of the fatty acid ethyl esters from
      butteroil has been investigated. The main objective of the present study was to
      obtain extracts rich in short- and medium-chain fatty acid ethyl esters. To that
      end, transesterification of the original butteroil was used to transform the
      triacylglycerols into the corresponding fatty acid ethyl esters. Then, several
      supercritical fluid extractions were carried out at pressures ranging from 8.9 to
      18.6 MPa and at 2 different temperatures (48 and 60 degrees C). The flow ratio of
      CO2 to butteroil was 15. Composition and yield of short- and medium-chain fatty
      acid ethyl esters was evaluated at different extraction conditions. Extracts
      containing approximately 70% short- and medium-chain fatty acid ethyl esters were
      obtained at 101 bar and 60 degrees C, and can be used as starting material for
      the production of highly valuable functional lipids.

PMID- 19389942
TI  - Detection of non-milk fat in milk fat by gas chromatography and linear
      discriminant analysis.
AB  - Gas chromatography was utilized to determine triacylglycerol profiles in milk and
      non-milk fat. The values of triacylglycerol were subjected to linear discriminant
      analysis to detect and quantify non-milk fat in milk fat. Two groups of milk fat
      were analyzed: A) raw milk fat from the central region of Mexico (n = 216) and B)
      ultrapasteurized milk fat from 3 industries (n = 36), as well as pork lard (n =
      2), bovine tallow (n = 2), fish oil (n = 2), peanut (n = 2), corn (n = 2), olive
      (n = 2), and soy (n = 2). The samples of raw milk fat were adulterated with non
      milk fats in proportions of 0, 5, 10, 15, and 20% to form 5 groups. The first
      function obtained from the linear discriminant analysis allowed the correct
      classification of 94.4% of the samples with levels <10% of adulteration. The
      triacylglycerol values of the ultrapasteurized milk fats were evaluated with the
      discriminant function, demonstrating that one industry added non-milk fat to its
      product in 80% of the samples analyzed.

PMID- 19389943
TI  - Production of fresh Cheddar cheese curds with controlled postacidification and
      enhanced flavor.
AB  - Cheddar cheese in curd form is very popular in eastern Canada. It is retailed
      immediately after cheese manufacturing and can be maintained at room temperature
      for 24 h to provide better texture and mouthfeel. Subsequently, the cheese curds
      must be stored at 4 degrees C. The shelf life is generally 3 d. In this study,
      Cheddar cheese curds were produced by adding a high diacetyl flavor-producing
      strain (Lactococcus diacetylactis) to a thermophilic-based starter. The objective
      was to achieve both postacidification stability to increase the shelf life and
      enhanced flavor. The addition of L. diacetylactis increased processing time but
      did not affect cheese composition or the evolution of proteolysis and texture.
      During cheese manufacturing, streptococci became the dominant microflora in all
      cheeses, whereas populations of Lactococcus cremoris and L. diacetylactis
      decreased. During cheese storage, viable counts of L. diacetylactis and
      Streptococcus thermophilus increased but the counts of L. cremoris decreased.
      During cheese manufacturing and storage, the concentrations of lactic acid and
      diacetyl increased rapidly in cheeses produced with L. diacetylactis. Citric acid
      and galactose contents remained high in cheese made without L. diacetylactis.
      Sensory evaluation indicated that cheeses containing the L. diacetylactis strain
      were more flavorful and also had less sourness and could be stored at 4 degrees C
      for up to 7 d.

PMID- 19389944
TI  - Effect of high-pressure homogenization on droplet size distribution and
      rheological properties of ice cream mixes.
AB  - The effect of different homogenization pressures (15/3 MPa and 97/3 MPa) on fat
      globule size and distribution as well as on structure-property relationships of
      ice cream mixes was investigated. Dynamic light scattering, steady shear, and
      dynamic rheological analyses were performed on mixes with different fat contents
      (5 and 8%) and different aging times (4 and 20 h). The homogenization of ice
      cream mixes determined a change from bimodal to monomodal particle size
      distributions and a reduction in the mean particle diameter. Mean fat globule
      diameters were reduced at higher pressure, but the homogenization effect on size
      reduction was less marked with the highest fat content. The rheological behavior
      of mixes was influenced by both the dispersed and the continuous phases. Higher
      fat contents caused greater viscosity and dynamic moduli. The lower
      homogenization pressure (15/3 MPa) mainly affected the dispersed phase and
      resulted in a more pronounced viscosity reduction in the higher fat content
      mixes. High-pressure homogenization (97/3 MPa) greatly enhanced the viscoelastic
      properties and the apparent viscosity. Rheological results indicated that
      unhomogenized and 15/3 MPa homogenized mixes behaved as weak gels. The 97/3 MPa
      treatment led to stronger gels, perhaps as the overall result of a network
      rearrangement or interpenetrating network formation, and the fat globules were
      found to behave as interactive fillers. High-pressure homogenization determined
      the apparent viscosity of 5% fat to be comparable to that of 8% fat unhomogenized
      mix.

PMID- 19389945
TI  - Fortification of reduced-fat Cheddar cheese with n-3 fatty acids: effect on off
      flavor generation.
AB  - The objective of this study was to fortify 50% reduced fat Cheddar cheese with n
      3 fatty acids and evaluate whether this fortification generated specific off
      flavors in the cheese. Docosahexaenoic (DHA) and eicosapentaenoic (EPA) fatty
      acids were added to the cheese to obtain 3 final fortification levels [18, 35,
      and 71 mg of DHA/EPA per serving size (28 g) of cheese] representing 10, 20, and
      40% of the suggested daily intake level for DHA/EPA. The presence of oxidized,
      rancid, and fishy flavors as a function of fortification level and cheese aging
      (6 mo) was evaluated using a sensory descriptive panel. No differences were found
      in the oxidized and rancid flavors as a consequence of DHA/EPA fortification,
      with only slight intensities of these flavors. The presence of fishy off-flavor
      was dependent on the fortification level. Cheeses with low fortification levels
      (18 and 35 mg of DHA/EPA per serving size) did not develop significant fishy off
      flavor compared with the control, whereas at the highest fortification level (71
      mg of DHA/EPA per serving size) the fishy off-flavor was significantly stronger
      in young cheeses. The fishy flavor decreased as a function of age and became
      nonsignificant compared with the control at 3 mo of storage. Even though fishy
      flavors were detected in the fortified cheeses, the DHA/EPA content during
      storage remained constant and complied with the suggested values for food
      fortification. Results obtained from this research indicate that 50% reduced-fat
      Cheddar cheese aged for 3 mo can be used as a vehicle for delivery of n-3 fatty
      acids without generation of off-flavors.

PMID- 19389946
TI  - Short communication: bovine kappa-casein variants result in different angiotensin
      I converting enzyme (ACE) inhibitory peptides.
AB  - Proteins in bovine milk are a common source of bioactive peptides. The peptides
      are released by the digestion of caseins and whey proteins. Peptides derived from
      the different genetic variants A, B, C, E, F1, F2, G1, G2, H, I, and J of bovine
      kappa-casein (CSN3) were investigated for their inhibitory activities against
      angiotensin I converting enzyme (ACE). Amino acid sequences of the CSN3 variants
      were analyzed in silico to detect potential ACE inhibitory peptides. Besides
      known biologically active peptides, exclusive peptides were identified in some
      CSN3 variants and their biological activity was determined: within CSN3*B and
      CSN3*C, the ACE inhibitory peptide ASP (IC50 = 242.3; the IC50 value is
      equivalent to the micromolar concentration of peptide mediating a 50% inhibition
      of ACE activity) and within CSN3*C the peptide AHHP (IC50 = 847.6) was detected.
      Furthermore, the peptides VSP (IC50 = 21.8) and ACHP (IC50 = 360.7) were
      identified in CSN3*F1 and CSN3*G2, respectively.

PMID- 19389947
TI  - Initiation and elongation steps of mRNA translation are involved in the increase
      in milk protein yield caused by growth hormone administration during lactation.
AB  - The underlying molecular mechanisms that control milk yield and milk protein
      yield in domestic animals are not completely understood. In this study, the
      galactopoietic response to exogenous growth hormone (GH) was used as an
      experimental model to investigate the role of translation initiation and
      elongation in the regulation of milk protein synthesis in the mammary gland. A
      slow-release formula of commercially available GH was administered via a single
      subcutaneous injection to 4 lactating cows (GH group). A further 4 cows were
      given a single subcutaneous injection of saline (control group). Changes in mRNA
      transcript level and protein phosphorylation status of key members of the
      mammalian target of rapamycin (mTOR) pathway were assessed in mammary gland
      tissues of these animals using quantitative real-time PCR and Western blotting.
      The GH treatment enhanced the phosphorylation of ribosomal protein S6 and
      increased the protein abundance of eukaryotic initiation factor 4E (eIF4E) and
      eukaryotic elongation factor 2 (eEF2) proteins in the mammary gland of GH-treated
      animals. These results indicate a link between milk protein synthesis and the
      regulation of mRNA translation. The GH treatment did not change mRNA abundance of
      ribosomal protein S6, eIF4E, and eEF2, nor did it change the mRNA (mTOR, eEF2
      kinase) or protein abundance of eEF2 kinase. These results demonstrate that GH
      administration changes mRNA translation initiation and elongation possibly via
      the mTOR pathway (suggested by the increased levels of ribosomal protein S6
      phosphorylation), indicating that the mTOR pathway might be a potential control
      point in the regulation of milk protein synthesis in the mammary gland.

PMID- 19389948
TI  - Impact of postpartum milking frequency on the immune system and the blood
      metabolite concentration of dairy cows.
AB  - The transition from pregnancy to lactation is marked by metabolic, hormonal, and
      immunological changes that have an impact on the incidence of infectious and
      metabolic diseases. The aim of this study was to evaluate the effect on immune
      function and blood metabolite concentration of limiting milk production in early
      lactation to reduce negative energy balance. Twenty-two multiparous Holstein cows
      were milked either once a day (1x) or twice a day (2x) for the first week
      postpartum. All cows were milked twice daily for the rest of lactation. Blood
      concentrations of nonesterified fatty acids (NEFA), beta-hydroxybutyric acid
      (BHBA), calcium, bilirubin, urea, phosphorus, glucose, leptin, stanniocalcin-1,
      and 17beta-estradiol were determined in samples collected from 5 wk before
      scheduled calving to 5 wk after calving. Polymorphonuclear leukocytes (PMNL) were
      isolated from blood to conduct assays for chemotaxis, phagocytosis, and
      respiratory burst. Peripheral blood mononuclear cells (PBMC) were isolated to
      evaluate lymphocyte proliferation and cytokine production (tumor necrosis factor
      alpha, IL-4, and interferon-gamma). Cows milked 1x produced 31% less milk than
      cows milked 2x during the first week of lactation. Over the following 13 wk of
      lactation, the milk production of cows milked 1x during the first week was 8.1%
      lower than for cows milked 2x. However, because the percentages of fat and
      protein were greater in the milk from 1x cows, the yields of milk components and
      energy-corrected milk were similar. Calving induced an increase in the
      concentrations of NEFA, BHBA, urea, and bilirubin. The increases in levels of
      NEFA and BHBA were greater in cows milked 2x than in cows milked 1x. During the
      same period, the serum glucose concentration decreased but remained greater in
      cows milked 1x. Serum calcium on d 4 and serum phosphorus on d 4 and 5 were
      greater in cows milked 1x. The differences between the 2 groups persisted beyond
      treatment until postpartum d 24 for NEFA and glucose and until postpartum d 14
      for BHBA. After calving, the concentrations of leptin and stanniocalcin-1
      decreased. During the first week postpartum, the decrease of leptin was less
      marked in cows milked 1x. The immune functions of PBMC and PMNL isolated from
      experimental cows and incubated using a standard medium did not show clear-cut
      peripartum immunosuppression. These variables were not significantly affected by
      the treatments, with the exception of interferon-gamma secretion, which was
      greater on d 5 and 14 in cows milked 1x. In conclusion, limiting milk production
      in early lactation had positive effects on metabolite concentration, but larger
      studies are necessary to establish if this could reduce disease incidence.

PMID- 19389949
TI  - Bovine coronary region keratinocyte colony formation is supported by epidermal
      dermal interactions.
AB  - Delineating the factors that orchestrate keratinocyte growth and differentiation
      in the claw is pivotal to understanding the quality of hoof horn production in
      health and disease. The specific objectives of this investigation were to
      establish an in vitro culture system for bovine coronary region keratinocytes and
      dermal fibroblasts, determine the colony-forming capacity of epidermal
      keratinocytes in the coronary region, and characterize transcriptional changes in
      specific cytokine, growth factor, and receptor genes during colony formation in
      coculture. Fibroblasts and keratinocytes from the coronary region of the lateral,
      hind limb claw were collected, and 5.0 x 10(3) and 7.5 x 10(3) keratinocytes were
      cultured in the presence or absence of fibroblast monolayers, respectively. The 2
      densities of keratinocytes formed 144 +/- 15.8 and 183 +/- 26.9 colonies,
      respectively, in the presence of dermal fibroblasts, whereas no colonies
      developed in the absence of dermal fibroblasts. Keratinocytes with the ability to
      show colony formation comprised 1.09% +/- 0.16 to 1.77% +/- 0.28 of the
      keratinocyte population isolated from the coronary region. Keratinocyte
      fibroblast cocultures developed a time-dependent increased expression of several
      growth factors, cytokines, and receptors. These findings demonstrated that
      keratinocytes from the bovine coronary region formed colonies in vitro and that
      colony formation occurred with an absolute dependence on dermal fibroblasts.
      Colony growth was associated with increased transcriptional expression of
      cytokine, growth factor, and receptor expression known to drive keratinocyte
      colony formation in other species. The results indicate that horn-producing
      keratinocytes must interact with dermal fibroblasts during normal tissue
      homeostasis in the bovine claw.

PMID- 19389950
TI  - Variation in hepatic regulation of metabolism during the dry period and in early
      lactation in dairy cows.
AB  - The purpose of this study was to investigate variations in hepatic regulation of
      metabolism during the dry period, after parturition, and in early lactation in
      dairy cows. For this evaluation, cows were divided into 2 groups based on the
      plasma concentration of beta-hydroxybutyric acid (BHBA) in wk 4 postpartum (PP;
      group HB, BHBA >0.75 mmol/L; group LB, BHBA <0.75 mmol/L, respectively). Liver
      biopsies were obtained from 28 cows at drying off (mean 59 +/- 8 d antepartum),
      on d 1, and in wk 4 and 14 PP. Blood samples were collected every 2 wk during
      this entire period. Liver samples were analyzed for mRNA abundance of genes
      related to carbohydrate metabolism (pyruvate carboxylase, PC; phosphoenolpyruvate
      carboxykinase, PEPCK; citrate synthase, CS), fatty acid biosynthesis (ATP citrate
      lyase, ACLY) and oxidation (acyl-CoA synthetase long-chain, ACSL; carnitine
      palmitoyltransferase 1A, CPT 1A; carnitine palmitoyltransferase 2, CPT 2; acyl
      coenzyme A dehydrogenase very long chain, ACADVL), cholesterol biosynthesis (3
      hydroxy-3-methylglutaryl-coenzyme A synthase 1, HMGCS1), ketogenesis (3-hydroxy-3
      methylglutaryl-coenzyme A synthase 2, HMGCS2), and of genes encoding the
      transcription factors peroxisome proliferator-activated receptor alpha
      (PPARalpha), peroxisome proliferator-activated receptor gamma (PPARgamma), and
      sterol regulatory element binding factor 1 (SREBF1). Blood plasma was assayed for
      concentrations of glucose, BHBA, nonesterified fatty acids, cholesterol,
      triglycerides, insulin, insulin-like growth factor-I, and thyroid hormones. In
      both groups, plasma parameters followed a pattern usually observed in dairy cows.
      However, changes were moderate and the energy balance in cows turned positive in
      wk 7 PP for both groups. Additionally, the energy balance and milk yield were
      similar for both groups after parturition onwards. Significant group effects were
      found at drying off, when plasma concentrations of triglycerides were higher in
      LB than in HB, and in wk 4 PP, when plasma concentrations of glucose and IGF-I
      were lower in HB than in LB. Similarly, moderate changes in mRNA expression of
      hepatic genes between the different time points were observed, although HB cows
      showed more adaptive performance than LB cows based on changes in mRNA expression
      of PEPCKc, PEPCKm, CS, CPT 1A, CPT 2, and PPARalpha. Part of the variation
      measured in this study was explained by parity. Significant Spearman rank
      correlation coefficients between the variables were not similar at each time
      point and were not similar between the groups at each time point, suggesting that
      metabolic regulation differs between cows. In conclusion, metabolic regulation in
      dairy cows is a dynamic system, and differs obviously between cows at different
      metabolic stages related to parturition.

PMID- 19389951
TI  - Factors affecting cure when treating bovine clinical mastitis with cephalosporin
      based intramammary preparations.
AB  - Data were collated for an independent scientific analysis from 2 international,
      multicenter studies that had compared the efficacy of 3 different cephalosporin
      containing intramammary preparations in the treatment of clinical mastitis in
      dairy cattle [cefalexin (first generation) in combination with kanamycin;
      cefquinome (fourth generation); and cefoperazone (third generation)]. Quarters
      were assessed using standard bacteriological techniques before treatment and at
      16 and 25 d posttreatment. Additional data were also available on individual cows
      and study farms, including parity, breed, and cow somatic cell count histories,
      herd bulk milk somatic cell counts, and farm management regimens. Sufficient data
      for analysis were available from a total of 491 cases on 192 farms in 3 countries
      (United Kingdom, France, and Germany) with up to 16 cases being recruited from
      any one farm. Clinical cases were of diverse etiology, representing both
      contagious and environmental pathogens. Univariable analysis demonstrated that
      quarters in the cefalexin + kanamycin and cefquinome treatment groups were not
      significantly different from each other, but were both significantly more likely
      to be pathogen free posttreatment than quarters in the cefoperazone group.
      Multivariable analysis was undertaken using conventional random effects models.
      Two models were built, with the first incorporating only information available to
      the practitioner at the time of treatment and the second including all
      information collected during the study. These models indicated that country,
      pretreatment rectal temperature (above-normal temperature associated with an
      increased chance of being pathogen free posttreatment), individual cow somatic
      cell count (increased somatic cell count associated with a decreased chance of
      being pathogen free posttreatment), and pathogen (Staphylococcus aureus isolation
      associated with a decreased chance of being pathogen free posttreatment) were
      useful predictors of pathogen free status; parity, yield, bulk milk somatic cell
      counts, and other farm management factors were not. The importance of country in
      the analysis demonstrates the need to generate local data when assessing
      treatment regimens. In addition, these results suggest that the factors important
      in predicting the outcome of treatment of clinical mastitis cases may be
      dissimilar to those reported to affect the likelihood of cure when treating
      subclinical intramammary infections.

PMID- 19389952
TI  - A necropsy-based descriptive study of dairy cow deaths on a Colorado dairy.
AB  - Increasing levels of dairy cow mortality pose a challenge to the US dairy
      industry. The industry's current understanding of dairy cow mortality is reliant
      upon descriptions largely based on producer or veterinary assumptions regarding
      cause of death without the benefit of detailed postmortem evaluations. A thorough
      necropsy is a superior tool for establishing a cause of death, except for cases
      involving euthanasia for traumatic accidents or severe locomotor disorders.
      Information provided from a necropsy examination would be most valuable if it
      were categorized and combined with cow health information in a complete
      postmortem evaluation designed to guide future management decisions. The
      objective of this study was to describe dairy cow deaths on a Colorado dairy over
      a 1-yr period and explore classification systems for necropsy findings that might
      inform management actions aimed at reducing dairy cow mortality. Throughout the
      study period a thorough necropsy examination was performed on every cow that
      died. Based upon this examination each death was characterized by a proximate
      cause (i.e., the most likely immediate cause of the death). Each proximate cause
      of death was then categorized using 3 alternate schemes founded on generalized
      etiologic principles and influenced by previous clinical history and treatments.
      These schemes included the broad categories commonly used for classifying
      findings within a review of literature related to dairy cow mortality, a
      diagnostic scheme used within the problem-oriented veterinary medical record, and
      an analysis focusing on the primary physiologic system derangement for each
      death. A total of 2,067 cows were enrolled during the study period of which 1,468
      cows freshened, 507 cows were sold, and 94 cows died, resulting in a mortality
      risk of 6.4 deaths per 100 lactations at risk. The distribution of deaths by
      parity was significantly different from the herd distribution at the end of study
      with the largest percentage of death present in parity > or =4. Postmortem
      findings attributable to a specific cause of death were present for all but 4 of
      the 94 deaths. Assignment of the proximate causes of death to categories within
      the 3 alternate schemes provided a means for classifying necropsy findings and
      causes of death with different levels of detail. Creating categories with more
      selective groupings may provide a means for capturing specifics related to deaths
      that can be used to guide management decisions.

PMID- 19389953
TI  - Effects of flunixin meglumine on pyrexia and bioenergetic variables in
      postparturient dairy cows.
AB  - Study objectives were to determine whether a nonsteroidal antiinflammatory drug
      would reduce parturition-induced inflammation and fever and consequently improve
      appetite, bioenergetic parameters, and production variables in transitioning
      dairy cows. Multiparous cows (n = 26) were randomly assigned to 1 of 2 treatments
      beginning at parturition: 1) flunixin meglumine (FM; 2.2 mg/kg of BW; Banamine,
      50 mg/mL, Schering-Plough Animal Health, Kenilworth, NJ), or 2) saline (control)
      at 2.0 mL/45.5 kg of BW. All treatments were administrated i.v. daily for the
      first 3 d in milk (DIM). Individual milk yield and dry matter intake (DMI) were
      recorded daily for the first 35 DIM. Rectal temperature was measured daily at
      0700 and 1600 h for the first 7 DIM. Milk composition was determined on 2, 7, 14,
      21, 28, and 35 DIM and blood plasma was collected on 1, 2, 3, 4, 7, 14, 21, 28,
      and 35 DIM. Body weight and body condition score were determined on -7, 1, 7, 14,
      21, 28, and 35 DIM. Flunixin meglumine treatment slightly increased rectal
      temperature (38.99 vs. 38.76 degrees C) during the first 7 DIM and reduced
      overall DMI (22.04 vs. 19.48 kg/d), but there were no treatment differences in
      overall milk yield (35.2 kg/d), 3.5% fat-corrected milk (37.6 kg/d), energy
      corrected milk (37.7 kg/d), DMI (2.97% of BW), or overall energy balance (-2.32
      Mcal/d). There were no treatment differences in milk fat (3.91%), protein
      (3.32%), or lactose (4.57%). Treatment had no effect on plasma glucose (66.5
      mg/dL) or nonesterified fatty acids (553 microEq/L), but plasma urea nitrogen
      tended to be less in FM-treated cows (16.4 vs. 14.5 mg/dL). Daily FM
      administration to cows for the first 3 d after parturition slightly increased
      rectal temperatures by 0.23 degrees C, reduced feed intake, and did not improve
      production or energetic variables during the first 35 DIM in transition dairy
      cows.

PMID- 19389954
TI  - Risk factors for increased rates of sole ulcers, white line disease, and digital
      dermatitis in dairy cattle from twenty-seven farms in England and Wales.
AB  - Claw lesion treatment records were recorded by farmers on 27 dairy farms (3,074
      cows, 36,432 records) in England and Wales between February 2003 and February
      2004. These were combined with farm environment and management data collected
      using a combination of direct observations, interviews with farmers, and milk
      recording data. Multilevel models were constructed for the 3 most frequently
      reported lesions related to lameness, namely, sole ulcers, white line disease,
      and digital dermatitis. Risks associated with an increased incidence of sole
      ulcers were parity 4 or greater, the use of roads or concrete cow tracks between
      the parlor and grazing, the use of lime on free stalls, and housing in free
      stalls with sparse bedding for 4 mo or more. The risks for white line disease
      were increasing parity and increasing herd size, cows at pasture by day and
      housed at night, and solid grooved concrete floors in yards or alleys. Solid
      grooved flooring was also associated with an increased risk of digital
      dermatitis, and cows 6 or more months after calving had a decreased risk of a
      first case of digital dermatitis. These results improve our understanding of the
      specific risks for 3 important lesions associated with bovine lameness and could
      be used as interventions in future clinical studies targeted at the reduction of
      specific lesions.

PMID- 19389955
TI  - Neck-rail position in the free stall affects standing behavior and udder and
      stall cleanliness.
AB  - This study tested the effect of neck-rail position on stall usage and udder and
      stall cleanliness. Thirty Holstein lactating cows were tested in groups of 6.
      Each group was tested with each of 5 neck-rail positions (130, 145, 160, 175, and
      190 cm from the rear curb, at a constant height of 125 cm above the bedded
      surface) for 1 wk, with the order of testing allocated in a 5 x 5 Latin square.
      When the neck rail was positioned further from the rear curb, cows spent less
      time standing with their front 2 hooves in the stall (2.2 +/- 0.26 h/d at 130 cm
      vs. 1.7 +/- 0.27 h/d at 190 cm, mean +/- SE) and more time standing with all 4
      hooves in the stall (0.0 +/- 0.02 h/d at 130 cm vs. 0.6 +/- 0.07 h/d at 190 cm).
      These effects of neck-rail position tended to be more marked for smaller cows,
      perhaps because the standing behavior of larger cows was restricted even in the
      190-cm treatment. Cows were more likely to defecate and urinate in the stalls
      when the neck rail was positioned further from the rear curb. Cows using these
      stalls tended to have dirtier udders and these stalls required more cleaning time
      (0.4 +/- 0.16 min/d at the 130-cm position vs. 1.6 +/- 0.35 min/d at the 190-cm
      position). In summary, positioning the neck rail further from the curb increased
      the time that cows spent standing fully in the stall. This change in standing
      behavior is likely beneficial for hoof health, but reduced udder and stall
      cleanliness.

PMID- 19389956
TI  - Effects of heat stress and plane of nutrition on lactating Holstein cows: I.
      Production, metabolism, and aspects of circulating somatotropin.
AB  - Heat stress is detrimental to dairy production and affects numerous variables
      including feed intake and milk production. It is unclear, however, whether
      decreased milk yield is primarily due to the associated reduction in feed intake
      or the cumulative effects of heat stress on feed intake, metabolism, and
      physiology of dairy cattle. To distinguish between direct (not mediated by feed
      intake) and indirect (mediated by feed intake) effects of heat stress on
      physiological and metabolic indices, Holstein cows (n = 6) housed in thermal
      neutral conditions were pair-fed (PF) to match the nutrient intake of heat
      stressed cows (HS; n = 6). All cows were subjected to 2 experimental periods: 1)
      thermal neutral and ad libitum intake for 9 d (P1) and 2) HS or PF for 9 d (P2).
      Heat-stress conditions were cyclical with daily temperatures ranging from 29.7 to
      39.2 degrees C. During P1 and P2 all cows received i.v. challenges of epinephrine
      (d 6 of each period), and growth hormone releasing factor (GRF; d 7 of each
      period), and had circulating somatotropin (ST) profiles characterized (every 15
      min for 6 h on d 8 of each period). During P2, HS cows were hyperthermic for the
      entire day and peak differences in rectal temperatures and respiration rates
      occurred in the afternoon (38.7 to 40.2 degrees C and 46 to 82 breaths/min,
      respectively). Heat stress decreased dry matter intake by greater than 35% and,
      by design, PF cows had similar reduced intakes. Heat stress and PF decreased milk
      yield, although the pattern and magnitude (40 and 21%, respectively) differed
      between treatments. The reduction in dry matter intake caused by HS accounted for
      only approximately 35% of the decrease in milk production. Both HS and PF cows
      entered into negative energy balance, but only PF cows had increased
      (approximately 120%) basal nonesterified fatty acid (NEFA) concentrations. Both
      PF and HS cows had decreased (7%) plasma glucose levels. The NEFA response to
      epinephrine did not differ between treatments but was increased (greater than
      50%) in all cows during P2. During P2, HS (but not PF) cows had a modest
      reduction (16%) in plasma insulin-like growth factor-I. Neither treatment nor
      period had an effect on the ST response to GRF and there was little or no
      treatment effect on mean ST levels or pulsatility characteristics, but both HS
      and PF cows had reduced mean ST concentrations during P2. In summary, reduced
      nutrient intake accounted for just 35% of the HS-induced decrease in milk yield,
      and modest changes in the somatotropic axis may have contributed to a portion of
      the remainder. Differences in basal NEFA between PF and HS cows suggest a shift
      in postabsorptive metabolism and nutrient partitioning that may explain the
      additional reduction in milk yield in cows experiencing a thermal load.

PMID- 19389957
TI  - Local control of mammary involution: is stanniocalcin-1 involved?
AB  - There is considerable evidence to indicate the existence of local control of
      mammary gland involution, but the exact nature of this control has yet to be
      defined. Stanniocalcin-1 (STC-1) is a newly discovered mammalian hormone that
      seems involved in the lactation process and may be implicated in the control of
      involution. As a first step in investigating this hypothesis, the change in STC-1
      levels in milk and serum was measured during drying off. Nine Holstein cows in
      late lactation were milked twice daily on half the gland, while the other half
      was left unmilked for a 14-d period. Milk and blood samples and mammary biopsies
      were taken on d -7, 1, 2, 7, and 14 relative to the onset of the nonmilking
      period. The concentrations of STC-1 in serum and milk were determined by RIA. The
      albumin concentration and proteinase activity of the milk were determined.
      Apoptosis of the mammary epithelium was quantified by terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling assay. Finally, the effects of milk
      on cellular activity and apoptosis were tested in vitro on mammary epithelial
      cells by measuring the turnover of tetrazolium salts and by counting the terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells. The
      drying off of 2 quarters increased the milk production of the quarters that were
      milked by 30%. Milk proteinase activity and BSA and STC-1 concentrations
      increased in the nonmilked quarters, but remained unchanged in the milked
      quarters. Moreover, at d 2, the apoptotic rate of the mammary cells was higher in
      the nonmilked quarters than in the milked quarters (0.22 +/- 0.04 vs. 0.07 +/-
      0.04%, respectively). Finally, in vitro experimentation demonstrated that mammary
      epithelial cells cultured in the presence of milk from involuting quarters had 3
      fold more apoptotic cells as compared with those cultured in milk from the milked
      quarters at d 14. The metabolic rate was reduced by 14.6% for milk from d 7 and
      23.6% for milk from d 14. Interestingly, the metabolic rate was negatively
      correlated with the STC-1 concentration in milk (r = -0.65). This study shows for
      the first time that STC-1 in milk is increased following milk stasis, although
      its exact role in the involution process remains to be clarified.

PMID- 19389958
TI  - Identification of internal control genes for quantitative polymerase chain
      reaction in mammary tissue of lactating cows receiving lipid supplements.
AB  - Dietary lipid supplements affect mammary lipid metabolism partly through changes
      in lipogenic gene expression. Quantitative PCR (qPCR) is a sensitive, reliable,
      and accurate technique for gene expression analysis. However, variation
      introduced in qPCR data by analytical or technical errors needs to be accounted
      for via normalization using appropriate internal control genes (ICG). Objectives
      were to mine individual bovine mammary microarray data on >13,000 genes across 66
      cows from 2 independent studies to identify the most suitable ICG for qPCR
      normalization. In addition to unsupplemented control diets, cows were fed
      saturated or unsaturated lipids for 21 d or were infused with supplements
      (butterfat, conjugated linoleic acid mixture, long-chain fatty acids) into the
      abomasum to modify milk fat synthesis and fatty acid profiles. We identified 49
      genes that did not vary in expression across the 66 samples. Subsequent gene
      network analysis revealed that 22 of those genes were not co-regulated. Among
      those COPS7A, CORO1B, DNAJC19, EIF3K, EMD, GOLGA5, MTG1, UXT, MRPL39, GPR175, and
      MARVELD1 (sample/reference expression ratio = 1 +/- 0.1) were selected for PCR
      analysis upon verification of goodness of BLAT/BLAST sequence and primer design.
      Relative expression of B2M, GAPDH, and ACTB, previously used as ICG in bovine
      mammary tissue, was highly variable (0.9 +/- 0.6) across studies. Gene stability
      analysis via geNorm software uncovered MRPL39, GPR175, UXT, and EIF3K as having
      the most stable expression ratio and, thus, suitable as ICG. Analysis also
      indicated that use of 3 ICG was most appropriate for calculating a normalization
      factor. Overall, the geometric average of MRPL39, UXT, and EIF3K is ideal for
      normalization of mammary qPCR data in studies involving lipid supplementation of
      dairy cows. These novel ICG could be used for normalization in similar studies as
      alternatives to the less-reliable ACTB, GAPDH, or B2M.

PMID- 19389959
TI  - Prevalence and antimicrobial susceptibility of gram-negative bacteria isolated
      from bovine mastitis between 2003 and 2008 in Korea.
AB  - The objective of this study was to assess trends in the prevalence and
      distribution of gram-negative bacteria isolated from bovine mastitis and their
      antimicrobial susceptibilities during a 6-yr period between 2003 and 2008 in
      Korea. Escherichia coli, Pseudomonas fluorescens, Klebsiella pneumoniae,
      Enterobacter cloacae, Acinetobacter lwoffi/junii, Pseudomonas aeruginosa, and
      Serratia marcescens were the most commonly observed pathogens during this period.
      Generally, gram-negative bacteria showed low susceptibilities to most of the
      antimicrobials tested in this study, except amikacin and gentamicin. Although
      these 2 aminoglycosides were broadly active against gram-negative bacteria, less
      than half of those bacteria showed susceptibilities to streptomycin. The beta
      lactams, except piperacillin, had the lowest activity among antimicrobials tested
      in this study. Susceptibilities to chloramphenicol and trimethoprim were fairy
      high in all genera of gram-negative bacteria, except Acinetobacter spp. and
      Pseudomonas spp., whereas relatively high resistance to tetracycline was observed
      uniformly among gram-negative bacteria. There was no significant change in the
      prevalence of bacterial and the proportion of antimicrobial resistance among gram
      negative bacteria isolates during a 6-yr period.

PMID- 19389960
TI  - Long-chain fatty acid effects on peroxisome proliferator-activated receptor-alpha
      regulated genes in Madin-Darby bovine kidney cells: optimization of culture
      conditions using palmitate.
AB  - Studying long-chain fatty acid (LCFA) effects on gene network expression in
      bovine cells could provide useful information for future practical applications.
      An optimized in vitro system that does not require tissue collection or cell
      isolation could fill a niche in the study of PPARalpha activity in ruminants.
      Specific aims were to optimize culture conditions in Madin-Darby bovine kidney
      (MDBK) cells to achieve maximal mRNA expression of known peroxisome proliferator
      activated receptor-alpha (PPARalpha) target genes using palmitate (16:0) as a
      representative LCFA. Variables included length of incubation time, use of albumin
      bound (4:1 molar proportion) 16:0 (A16:0), or addition of insulin. A first time
      course experiment tested culturing cells in Dulbecco's modified Eagle's medium
      with 150 microM PPAR ligand Wy-14643 (WY) and A16:0. A second experiment tested
      the effects of albumin and insulin using 150 microM of 16:0 without albumin or
      insulin (-Alb/-Ins), 16:0 without albumin plus 5 mg/L of bovine insulin (
      Alb/+Ins), A16:0 without insulin (+Alb/-Ins), or a control. A third experiment
      was a preliminary metabolic characterization of cells and assessed intracellular
      lipid droplet formation after treatment with 150 microM of 16:0 or an ethanol
      control. For all experiments, cells were harvested at 0, 6, 12, 18, and 24 h
      posttreatment. In experiments 1 and 2, mRNA expression was assessed by
      quantitative PCR of selected PPARalpha target genes as well as PPARalpha
      coactivators (ACOX1, CPT1A, ACADVL, ACSL1, PPARA, PPARGC1A, LPIN1). In experiment
      1, there was a linear increase in mRNA expression of CPT1A (approximately 500%)
      and ACSL1 (50 to 200%) by 6 h of incubation with both WY and A16:0. The LPIN1
      mRNA increased by >100% by 6 h only with A16:0. Further, there was a linear
      increase in expression of PPARA (approximately 100%) with A16:0 through 24 h of
      incubation. In experiment 2, insulin increased, and coupling LCFA with albumin
      tended to delay the response in expression of CPT1A and ACSL1 to 16:0. Data
      indicated a toxic effect of 150 microM free 16:0 as assessed by cell counts after
      12 h of incubation. In experiment 3, MDBK cells appeared to use glucose and AA as
      energy sources and were able to secrete triglycerides. In addition, MDBK cells
      cultured with 150 microM of 16:0 had a substantial uptake of LCFA and synthesized
      intracellular lipid droplets. Overall, results indicated that a 6-h incubation
      with free LCFA and addition of insulin was suitable to detect marked effects on
      mRNA expression of PPARalpha target genes in MDBK cells.

PMID- 19389961
TI  - Technical note: assessing the functional capacity of mitochondria isolated from
      lactating mammary tissue: choose your chelating agent wisely.
AB  - Previous work has indicated that respiratory activity of mitochondrial
      preparations prepared from lactating mammary tissue is often much lower than that
      of mitochondria isolated from other organs such as the liver. Initial studies in
      our own laboratory also found that mammary mitochondria prepared from lactating
      mice had much lower ATP synthesis activity than those isolated from liver tissue
      obtained from the same animals. In this paper, we describe an improved procedure
      for obtaining coupled mitochondria from the mammary tissue of lactating mice.
      Using a high-throughput assay for mitochondrial ATP synthesis, we demonstrated
      that mammary mitochondria, unlike liver mitochondria, are sensitive to the
      concentration of bovine serum albumin and to the choice of chelating agent used
      in the preparation and assay buffers. Mammary mitochondria prepared and assayed
      in buffers containing 1 mM ethylene glycol-bis-(beta-aminoethyl ether)-N,N'
      tetraacetic acid (EGTA) and 0.4% bovine serum albumin have a similar ATP
      synthesis activity as liver mitochondria. In addition, we show that the chelating
      agent EDTA ablates the ATP synthesis capacity of mammary mitochondria through a
      mechanism that does not involve the release of cytochrome c. We also demonstrate
      that these improved isolation and assay procedures are both scalable and
      applicable to bovine mammary tissue, and we describe optimal conditions for
      cryopreservation and recovery of functionally active mitochondria. This work will
      facilitate future studies aimed at determining the importance of mammary
      mitochondria to milk production.

PMID- 19389962
TI  - Hot topic: pathway confirmed for the transmission of melamine from feed to cow's
      milk.
AB  - Eight lactating Holstein cows were randomly allotted to 2 groups in a trial to
      establish whether a pathway exists for the transmission of melamine from feed to
      milk. All cows received oat hay ad libitum and 15 kg of concentrate pellets per
      cow daily. The concentrate pellets contained either melamine-contaminated corn
      gluten meal of Chinese origin (melamine treatment) or locally produced melamine
      free corn gluten meal (control treatment). Cows in the melamine treatment
      ingested 17.1 g of melamine per day. Cows were milked twice daily, and milk
      samples were taken once daily during the afternoon milking for melamine and milk
      component analyses. Melamine appeared in the milk within 8 h after first
      ingestion of the melamine containing pellets. Melamine concentration reached a
      maximum of 15.7 mg/kg within 56 h after first ingestion, with an excretion
      efficiency of approximately 2%. Milk solids and milk urea nitrogen were not
      affected by treatment. The melamine concentration dropped rapidly after changing
      all cows back to the control pellets, but melamine only declined to undetectable
      levels in the milk more than 6 d (152 h) after last ingestion of melamine.
      Results from the current trial are important to the feed and dairy industries
      because, until now, any melamine found in milk and milk products was attributed
      only to the deliberate external addition of melamine to these products, not to
      adulterated ingredients in animal feeds.

PMID- 19389963
TI  - Calcium salts of polyunsaturated fatty acids deliver more essential fatty acids
      to the lactating dairy cow.
AB  - Recent research has focused on the importance of supplying essential fatty acids
      to the lactating dairy cow. The addition of essential fatty acids, specifically
      linoleic and linolenic acid, to dairy cow diets has been investigated as a method
      to increase reproductive efficiency. Rumen bacteria, however, biohydrogenate
      polyunsaturated fatty acids (PUFA) to saturated fatty acids. This is an important
      issue because it can also lead to milk fat depression when unsaturated fatty
      acids are fed. The formation of Ca salts has previously been shown to partially
      protect unsaturated fatty acids from rumen biohydrogenation. The objective of
      this experiment was to evaluate feed intake, milk production, and milk
      composition of cows fed Ca salts of palm fatty acids (CS) compared with those fed
      Ca salts of palm fatty acids with an increased content of PUFA (CS+PUFA).
      Nineteen lactating Holstein cows were used in a switchback experiment to
      determine any differences between CS and CS+PUFA on milk production and
      composition. This experiment consisted of 3 consecutive periods of 14 d.
      Treatments were formulated to provide 450 g/d (dry matter basis) of the Ca salt
      supplement and were mixed with the same basal ration. Milk weights and feed
      intakes were recorded daily for each cow. Milk samples were collected the last 2
      d of each period and analyzed for milk composition and fatty acids. Dry matter
      intake [28.0 vs. 27.0 kg/d; standard error of the mean (SEM) = 0.4] and milk
      production (44.4 vs. 44.0 kg/d; SEM = 0.7) were not different between treatments
      for CS and CS+PUFA, respectively. Milk fat percentage (3.34 vs. 3.22%; SEM =
      0.07) and milk protein percentage (2.78 vs. 2.80%; SEM = 0.01) were not different
      for CS- and CS+PUFA-fed cows. Feeding CS+PUFA reduced the concentration of
      palmitic acid in milk fat (28.3 vs. 26.8 wt%; SEM = 0.3). Supplementation of
      CS+PUFA increased the linoleic acid concentration (3.96 vs. 4.61 wt%; SEM = 0.1)
      of milk fat, indicating that linoleic acid was partially protected from rumen
      biohydrogenation. Concentrations of conjugated linoleic acid were also increased
      (0.44 vs. 0.52 wt%; SEM = 0.02) when cows consumed CS+PUFA, indicating that some
      biohydrogenation did occur. Supplementing CS+PUFA did not alter milk production,
      milk fat percentage, or dry matter intake when compared with CS. The CS+PUFA
      supplement supplied more linoleic acid to the small intestine for milk fat
      synthesis.

PMID- 19389964
TI  - Potentials to differentiate milk composition by different feeding strategies.
AB  - To investigate the effect of the dietary intake of the cow on milk composition,
      bulk-tank milk was collected on 5 occasions from conventional (n = 15) and
      organic (n = 10) farms in Denmark and on 4 occasions from low-input nonorganic
      farms in the United Kingdom, along with management and production parameters.
      Production of milk based on feeding a high intake of cereals, pasture, and grass
      silage resulted in milk with a high concentration of alpha-linolenic acid (9.4 +/
      0.2 mg/kg of fatty acids), polyunsaturated fatty acids (3.66 +/- 0.07 mg/kg of
      fatty acids), and natural stereoisomer of alpha-tocopherol (RRR-alpha-tocopherol,
      18.6 +/- 0.5 mg/kg of milk fat). A milk production system using a high proportion
      of maize silage, by-products, and commercial concentrate mix was associated with
      milk with high concentrations of linoleic acid (LA; 19.7 +/- 0.4 g/kg of fatty
      acids), monounsaturated fatty acids (27.5 +/- 0.3 mg/kg of fatty acids), and a
      high ratio between LA and alpha-linolenic acid (4.7 +/- 0.2). Comparing these 2
      production systems with a very extensive nonorganic milk production system
      relying on pasture as almost the sole feed (95 +/- 4% dry matter intake), it was
      found that the concentrations of conjugated LA (cis-9,trans-11; 17.5 +/- 0.7 g/kg
      of fatty acids), trans-11-vaccenic acid (37 +/- 2 g/kg of fatty acids), and
      monounsaturated fatty acids (30.4 +/- 0.6 g/kg of fatty acids) were higher in the
      extensively produced milk together with the concentration of antioxidants; total
      alpha-tocopherol (32.0 +/- 0.8 mg/kg of milk fat), RRR-alpha-tocopherol (30.2 +/-
      0.8 mg/kg of milk fat), and beta-carotene (9.3 +/- 0.5 mg/kg of milk fat)
      compared with the organic and conventional milk. Moreover, the concentration of
      LA (9.2 +/- 0.7 g/kg of fatty acids) in milk from the extensive milk production
      system was found to approach the recommended unity ratio between n-6 and n-3,
      although extensive milk production also resulted in a lower daily milk yield.

PMID- 19389966
TI  - Digestion and nitrogen utilization in dairy heifers limit-fed a low or high
      forage ration at four levels of nitrogen intake.
AB  - The hypothesis of this experiment is that a low-forage (LF) ration will be
      utilized with greater efficiency than a high-forage ration (HF) by dairy heifers
      and that the response will be affected by level of N intake. To test this
      hypothesis, 8 Holstein heifers (beginning at 362 +/- 7 kg and 12.3 +/- 0.4 mo)
      were fed 8 rations according to a split-plot, 4 x 4 Latin square design.
      Treatments were formulated to contain 25 or 75% forage (corn silage and chopped
      wheat straw) and fed at 4 levels of N intake [0.94 (Low), 1.62 (MLow), 2.30
      (MHigh), 2.96 (High) g of N/kg of metabolic body weight per day]. Diets were
      limit-fed to maintain equal intake of metabolizable energy. Blood samples were
      collected over d 19 to 20, and feces and urine were collected for 8 d per 28-d
      period. Organic matter (OM) intake was greater for heifers fed HF, but, due to
      increased OM digestibility of LF (74.0 vs. 67.6% +/- 0.9), digestible OMI was
      unaffected by forage level. Organic matter digestibility was affected by an
      interaction between forage level and N intake, increasing to a plateau of 78.01%
      at 18.43% crude protein for LF-fed and 68.78% at 13.90% crude protein for HF-fed
      heifers. Apparent N digestibility was greater for heifers fed LF and increased
      from 47.7 to 80.8% between Low and High N intake. Less N appeared in the feces of
      heifers fed LF than HF (45.56 vs. 52.60 g/d). Urea-N excretion was not different
      between forage levels, but increased linearly with N intake. Concentration of
      plasma urea-N was significantly higher for LF and with increasing N intake. Urea
      clearance rate (L/h) did not differ between forage levels and increased, but at a
      decreasing rate, as N intake increased. A significant interaction resulted from
      urea clearance increasing at a greater rate and resulting in higher values for
      HF, whereas clearance of urea for heifers fed LF resulted in significantly lower
      maximal values. Like urea-N excretion, daily urinary N excretion was affected
      only by N intake. Retained N responded linearly to increased levels of N intake.
      The significant reduction observed in fecal N excretion for LF was
      counterbalanced by numerical increases in urinary N excretion so that total N
      excretion and retention were not different between forage levels. The percentage
      of N intake that was retained only tended to be affected by an interaction and
      was not significantly affected by forage level. It is concluded that increasing N
      intake increases the digestibility of OM, the magnitude of which depends on the
      level of dietary forage provided. Furthermore, differences in N utilization
      between LF and HF in this trial were small and were not evident until N intake
      increased to impractical levels.

PMID- 19389965
TI  - Timothy silage with low dietary cation-anion difference fed to nonlactating cows.
AB  - Decreasing the dietary cation-anion difference (DCAD) by using anion sources
      before calving reduces hypocalcemia in cows at calving. Reduced DCAD from CaCl2
      fertilized timothy hay achieves similar results, but the effects of feeding low
      DCAD forage as silage have not been determined. The objective of this study was
      to evaluate the effect of low-DCAD timothy silage on dry cows. Six nonlactating
      and nonpregnant Holstein cows were used in a replicated 3 x 3 Latin square.
      Treatments were 1) control diet (DCAD = 232 mEq/kg of dry matter, DM); 2) low
      DCAD diet using a low-DCAD timothy silage (LDTS; DCAD = -21 mEq/kg of DM); and 3)
      low-DCAD diet using a fermentation by-product (LDBP; DCAD = -32 mEq/kg of DM).
      Differences between dietary treatments were considered statistically significant
      at P < or = 0.05 and tendencies were noted when 0.05 < P < 0.10. Compared with
      the control, feeding LDTS tended to decrease DM intake (10.6 vs. 12.5 kg/d) and
      decreased urinary pH (6.15 vs. 8.18) as well as apparent digestibility of DM (67
      vs. 69%). Blood pH (7.37 vs. 7.42), HCO3- (25.3 vs. 27.5 mM), and base excess
      (0.4 vs. 3.1 mM) were decreased, and blood Cl- (29.6 vs. 29.1 mg/dL) was
      increased. Apparently absorbed Na and Cl were higher and apparently absorbed K,
      P, and digested ADF were lower for LDTS compared with the control. Both LDTS and
      LDBP resulted in similar DM intake. Urinary pH tended to be higher (6.15 vs.
      5.98) and percentage of digested DM was lower (67 vs. 70%) with LDTS compared
      with LDBP. Blood ionized Ca (5.3 vs. 5.4 mg/dL) tended to be lower and blood Cl-
      (29.6 vs. 30.1 mg/dL) was lower, whereas blood pH (7.37 vs. 7.33), HCO3- (25.3
      vs. 21.5 mM), and base excess (0.4 vs. -3.8 mM) were higher with LDTS compared
      with LDBP. Apparent absorption of Na, Cl, S, and P, as well as apparent digestion
      of acid detergent fiber, neutral detergent fiber, and N were lower, and K, Cl, S,
      P, Mg, and N were less retained with LDTS compared with LDBP. Results confirm
      that low-DCAD timothy silage can be used to produce a compensated metabolic
      acidosis by decreasing the DCAD of rations served to nonlactating dairy cows.

PMID- 19389967
TI  - Effects of rumen fill on short-term ingestive behavior and circulating
      concentrations of ghrelin, insulin, and glucose of dairy cows foraging vegetative
      micro-swards.
AB  - The objective of this study was to investigate changes in foraging behavior,
      hunger-related hormones, and metabolites of dairy cows in response to short-term
      variations in rumen fill (RF). The effect of RF on intake rate, jaw movements,
      bite rate and dimensions, and concentrations of plasma ghrelin, and serum insulin
      and glucose were measured in 4 rumen-cannulated lactating dairy cows (612 +/- 68
      kg, empty live weight; 237 +/- 29 d in milk) foraging micro-swards of vegetative
      orchardgrass (Dactylis glomerata L.). The treatments compared were the removal of
      different proportions of total rumen contents: 1.00 (RF0), 0.66 (RF33), 0.33
      (RF66), or 0 (RF100). Treatments were randomly applied 2 h before foraging
      sessions in a 4 x 4 Latin square design. Micro-swards were weighed before and
      after foraging sessions. Cows were allowed to take a maximum of 15 bites with no
      time restriction. Eating time, intake rate, total jaw movements, and bite mass,
      depth, area, and rate were determined. Plasma was analyzed for ghrelin and serum
      for insulin and glucose immediately before and 2 h after the treatments were
      applied. Intake rate, bite mass, and bite area increased, whereas bite depth
      decreased as RF decreased. The RF did not affect bite rate or total jaw
      movements. Decreasing RF resulted in increased plasma concentrations of ghrelin
      and tended to increase serum insulin, with reduced concentrations of serum
      glucose. Incremental variation in plasma ghrelin and serum insulin correlated
      with bite depth and mass, whereas changes in serum glucose correlated with intake
      rate, bite area, depth and mass, as well as with herbage intake per jaw movement.
      The present study elucidates some of the underlying endocrine physiology of
      cattle with short-term temporal variations of RF and their effects on some
      components of foraging behavior.

PMID- 19389968
TI  - Liver phosphorus content in Holstein-Friesian cows during the transition period.
AB  - Hepatic lipidosis and hypophosphatemia are frequently observed in high-yielding
      periparturient dairy cows. Objectives of this study were to investigate the
      association of the liver P content with the degree of liver fat accumulation and
      serum P concentration and to characterize the change in liver P content
      throughout the transition period. In a cross-sectional study, liver biopsies
      obtained from 33 Holstein-Friesian cows 14 d postpartum (p.p.) were assayed for
      total lipid (TLip), triacylglycerol, DNA, P, Mg, K, Na, and Ca content. Serum
      samples obtained at the time of biopsy were analyzed for indices of liver
      function and injury and the serum P concentration was determined. From this cross
      sectional study, 6 cows were selected for a longitudinal study and liver tissue
      obtained from the 6 cows on d -65, -30, -14, 1, 14, 28, and 49 relative to
      calving was assayed. The amounts of P, K, Mg, Na, and Ca were expressed as amount
      in dry weight (DW), wet weight (WW), nonfat wet weight (NFWW), and indexed to
      DNA. In the cross-sectional study, P(DW) and P(WW) decreased with increasing
      TLip, whereas P(NFWW) and P(DNA) were independent of TLip. Values for P(DNA)
      varied widely, whereas P(NFWW) varied within a narrow range. Stepwise regression
      analysis revealed the strongest associations between P(DW) and the amount of
      tissue water (partial R2 = 0.74) and the log to the base 10 of triacylglycerol
      (partial R2 = 0.05). The P(WW) was associated with the log to the base 10 of
      triacylglycerol (partial R2 = 0.20), but no associations were found for P(NFWW).
      These findings indicate that decreased electrolyte content in dry and wet liver
      tissue with increased liver lipid content is predominantly due to the decrease in
      tissue water and therefore the distribution volume of electrolytes. In the
      longitudinal study, P(DW), P(WW), and P(NFWW) were decreased on d 14 p.p. Similar
      directional decreases were found for K, Mg, and Na, but P was the only
      electrolyte that was significantly decreased in liver tissue at d 14 p.p. This
      finding indicates that the P content of liver tissue decreases in early lactation
      due to a reduction in hepatocellular cytosol volume as well as a decrease in
      cytosolic P concentration, with the latter having biological relevance. The
      clinical significance of decreased cytosolic P concentration in the hepatocytes
      of dairy cows in early lactation remains to be determined.

PMID- 19389969
TI  - Crushed sunflower, flax, or canola seeds in lactating dairy cow diets: effects on
      methane production, rumen fermentation, and milk production.
AB  - The objective of this study was to investigate the potential of reducing enteric
      methane production from dairy cows by incorporating into the diet various sources
      of long-chain FA varying in their degree of saturation and ruminal availability.
      The experiment was conducted as a crossover design with 16 lactating dairy cows
      maintained in 2 groups and fed 4 dietary treatments in four 28-d periods. Eight
      ruminally cannulated primiparous cows (96 +/- 18 d in milk) were assigned to
      group 1 and 8 multiparous cows (130 +/- 31 d in milk) were assigned to group 2.
      The dietary treatments were: 1) a commercial source of calcium salts of long
      chain fatty acids (CTL), 2) crushed sunflower seeds (SS), 3) crushed flaxseed
      (FS), and 4) crushed canola seed (CS). The oilseeds added 3.1 to 4.2% fat to the
      diet (DM basis). All 3 oilseed treatments decreased methane production (g/d) by
      an average of 13%. When corrected for differences in dry matter intake (DMI),
      compared with CTL, methane production (g/kg of DM intake) was decreased by
      feeding FS (-18%) or CS (-16%) and was only numerically decreased (-10%) by
      feeding SS. However, compared with the CTL, feeding SS or FS lowered digestible
      DMI by 16 and 9%, respectively, because of lowered digestibility. Thus, only CS
      lowered methane per unit of digestible DM intake. Feeding SS and CS decreased
      rumen protozoal counts, but there were no treatment effects on mean ruminal pH or
      total volatile fatty acid concentration. Milk efficiency (3.5% fat corrected
      milk/DMI), milk yield, and component yield and concentrations were not affected
      by oilseed treatments. The study shows that adding sources of long-chain fatty
      acids to the diet in the form of processed oilseeds can be an effective means of
      reducing methane emissions. However, for some oilseeds such as SS or FS, the
      reduction in methane can be at the expense of diet digestibility. The use of
      crushed CS offers a means of mitigating methane without negatively affecting diet
      digestibility, and hence, milk production.

PMID- 19389970
TI  - Effects of level and form of dietary zinc on dairy cow performance and health.
AB  - A basal mixed ration supplying 36 mg of Zn/kg of dry matter (DM) was supplemented
      with 1 of 4 concentrates differing in level and form of dietary Zn. The
      concentrates were fed at 2 kg/cow per day and contained 300 mg of Zn/kg (to
      supply the total recommended level, according to NRC (2001); R) or 60 mg of Zn/kg
      (to supply 0.66 of the total recommended level; L), either supplemented as ZnO
      (I) or organically chelated Zn (O). Forty-four Holstein-Friesian dairy cows (12
      primiparous and 32 multiparous), on average 31 d (SD +/- 11.4) into lactation,
      were allocated to 1 of the 4 treatments. All cows remained on the treatment for
      14 wk. The data was analyzed by ANOVA as a 2 x 2 factorial design. Dry matter
      intake averaged 23.5 kg/d and did not differ between treatments. Cows
      supplemented with organically chelated Zn at the recommended level of inclusion
      (RO) had a higher milk yield (37.6 kg/d) than those fed inorganic Zn at the
      recommended level (RI; 35.2 kg/d) or organically chelated Zn at the low level
      (LO; 35.2 kg/d), but was not different from those fed inorganic Zn at the low
      level (LI; 36.0 kg/d). Milk composition was unaffected by dietary treatment.
      Animals that received the low level of Zn (LI and LO) had higher somatic cell
      counts [3.97 and 3.93 versus 4.35 and 4.55 (log(e)) for RI, RO, LI, and LO,
      respectively] and milk amyloid A levels than those receiving the recommended
      levels (RO and RI). There was no effect of treatment on body condition score,
      body weight, or locomotion score. Hoof hardness improved over the duration of the
      study but there were no differences between treatments. Similarly, blood plasma
      mineral levels for Zn, Cu, Mo, and Fe were not affected by treatment, whereas
      there was a trend for increased ceruloplasmin levels in cows receiving the
      recommended compared with the low level of Zn, but there was no effect of mineral
      form. There was also no effect of treatment on superoxide dismutase activity or
      blood hematology. It is concluded that supplementing Zn at the recommended level
      reduced somatic cell counts and milk amyloid A levels, whereas supplementation in
      an organic form at the recommended level also increased milk yield.

PMID- 19389971
TI  - Genome scan detects quantitative trait loci affecting female fertility traits in
      Danish and Swedish Holstein cattle.
AB  - Data from the joint Nordic breeding value prediction for Danish and Swedish
      Holstein grandsire families were used to locate quantitative trait loci (QTL) for
      female fertility traits in Danish and Swedish Holstein cattle. Up to 36 Holstein
      grandsires with over 2,000 sons were genotyped for 416 microsatellite markers.
      Single trait breeding values were used for 12 traits relating to female fertility
      and female reproductive disorders. Data were analyzed by least squares regression
      analysis within and across families. Twenty-six QTL were detected on 17 different
      chromosomes. The best evidence was found for QTL segregating on Bos taurus
      chromosome (BTA)1, BTA7, BTA10, and BTA26. On each of these chromosomes, several
      QTL were detected affecting more than one of the fertility traits investigated in
      this study. Evidence for segregation of additional QTL on BTA2, BTA9, and BTA24
      was found.

PMID- 19389972
TI  - Nongenetic effects and genetic parameters for length of productive life of
      Holstein cows in Hokkaido, Japan.
AB  - Records of Holstein dairy cows in Hokkaido, Japan, were used to study the effects
      of environmental factors on length of productive life and to estimate genetic
      parameters for length of productive life. Each record was assigned to 1 of 3 data
      sets depending on the percentage of type-scored cows in the herd. This percentage
      was considered to partly reflect the management policy in each herd, in
      particular regarding culling. The A, B, and C data sets consisted of herds with
      none, less than 60%, and more than 60% of type-scored cows, respectively, and
      included 158,719, 787,598, and 131,499 records, respectively. Analyses of length
      of productive life were separately carried out on each data set using the
      Survival Kit software (Version 5.0). Nonparametric hazards estimates and the
      shape parameters of the baseline Weibull distribution differed between the 3 data
      sets. A cow having a sire originating from the United States or Canada had a
      relatively lower risk of being culled than a cow having Japanese sire in data set
      C. However, in data set A, a cow having a Canadian sire had a higher relative
      risk than a cow having a Japanese sire. The herd-year variance for data set A was
      about twice as large as for data set C. In contrast, the sire variance for data
      set A was about 40% of the one for data set C. As a result, heritability varied
      across data sets from 0.046 to 0.134. The results of this study suggest that it
      is important to consider factors related to herd management policy, such as the
      percentage of type-scored cows, in genetic analyses on length of productive life
      of Holstein cows in Hokkaido, Japan.

PMID- 19389973
TI  - Genetic analysis of lactoferrin content in bovine milk.
AB  - Bovine lactoferrin (LF) is mainly present in milk and shows important
      physiological and biological functions. The aim of this study was to estimate the
      heritability and correlation values of LF content in bovine milk with different
      economic traits as milk yield (MY), fat and protein percentages, and somatic cell
      score (SCS). Variance components of the studied traits were estimated by REML
      using a multiple-trait mixed model. The obtained heritability (0.22) for LF
      content predicted using mid-infrared spectrometry (pLF) suggested the possibility
      of animal selection based on the increase of LF content in milk. The phenotypic
      and genetic correlation values calculated between pLF and SCS were moderate (0.31
      and 0.24, respectively). Furthermore, a preliminary study of bovine LF gene
      polymorphism effects was performed on the same production traits. By PCR, all
      exons of the LF gene were amplified and then sequenced. Three new polymorphisms
      were detected in exon 2, exon 11, and intron 8. We examined the effects of LF
      gene polymorphisms of exons 2, 4, 9, 11, and 15, and intron 8 on pLF, MY, fat and
      protein percentages, and SCS. The different observed effects did not reach a
      significant level probably because of the characteristics of the studied
      population. However, the results were promising, and LF may be a potential
      indicator of mastitis. Further studies are necessary to evaluate the effect of
      genetic selection based on LF content on the improvement of mastitis resistance.

PMID- 19389974
TI  - Commencement of luteal activity in three different selection lines for milk yield
      and fertility in Norwegian Red cows.
AB  - Relationships among commencement of luteal activity (C-LA), milk yield, and
      energy balance (EB) were investigated in 3 selection lines of Norwegian Red cows
      at the Norwegian University of Life Sciences from 1994 through 2001. The cows
      were selected for low genetic merit for milk yield (LMP), high genetic merit for
      milk yield (HMP), and a combination of high indices for milk yield and fertility
      (HI). Breeding values for fertility were based on 56-d nonreturn rate. The
      material included 268 lactations from 147 cows. Milk samples for progesterone
      analysis were drawn 3 times weekly from 1994 through 1998, and 2 times weekly
      from 1999 to 2001. Commencement of luteal activity was defined as the first 2
      consecutive measurements of progesterone concentration >3 ng/mL not earlier than
      10 d after calving. Selection line was significantly related to C-LA, so that the
      least squares mean days from calving to C-LA were 22.5, 30.4, and 27.2 d for LMP,
      HMP, and HI cows, respectively. The HMP cows produced more milk than the LMP
      cows. The average milk yield in the sixth week of lactation was 24.0, 27.1, and
      25.3 kg for LMP, HMP, and HI cows, respectively. The interval to C-LA decreased
      for the HMP and HI cows after phenotypic adjustment for EB in the model. Least
      squares means for the interval to C-LA were 23.2, 29.7, and 25.6 d for the LMP,
      HMP, and HI cows, respectively, in a model that included parity, selection lines,
      and EB as covariates. Cumulated EB during the first 4 wk of lactation, which
      itself differed between selection lines, did not fully account for differences in
      interval to C-LA between selection lines. Thus, the results of the present
      investigation indicate that selection for milk yield negatively affects C-LA over
      and above the effects caused by concurrent changes in EB. The increase in days to
      C-LA caused by selection for high yields can be reduced if selection for milk
      yield is combined with fertility in the breeding program.

PMID- 19389975
TI  - Graphical approach to evaluate genetic estimates of calf survival.
AB  - Genetic variation and resemblance among relatives are fundamentals of
      quantitative genetics. Our purpose was to identify bulls with a bimodal pattern
      of inheritance in the quest for new discoveries about the inheritance of calf
      survival. A bimodal pattern of inheritance for calf survival was identified in
      sons of Holstein bulls. A bimodal pattern of inheritance indicates 2 groups of
      sons resulting from an allele effect, a grandsire effect, or some other common
      factor. Different combinations (AA, Aa, aa) of 2 alleles at a locus cause varying
      phenotypes to be expressed. Bulls that are heterozygous for loci affecting
      reproductive performance may have a bimodal pattern of inheritance if the
      difference in effect of the 2 alleles is large. If the bimodal pattern is caused
      by an allele effect, then molecular markers can be identified for use in marker
      assisted selection breeding programs. Data on predicted transmitting ability for
      perinatal survival for the first parity of 8,678 sons of 599 sires were collected
      from 1984 through 1997 from the National Association of Animal Breeders calving
      ease database, which included 7 Midwestern states. Sixteen bulls were identified
      with a potential bimodal pattern of inheritance because they had 2 distinct
      groups of sons. The 2 groups of sons were separated by calculating the
      coefficient of variation for each possible combination of sons; the combination
      that gave the smallest coefficient of variation difference between the 2 groups
      was considered the correct distribution of the sons into those groups. Bulls with
      a bimodal distribution were analyzed to determine the distribution of the
      grandsons among the maternal grandsires (MGS) of the 2 groups of the bimodal
      distribution. The bimodal distribution may be a result of heterozygous sires or
      MGS that are homozygous for low or high survival. If the bimodal distribution is
      caused by a MGS effect, then marker-assisted selection can still be used by
      evaluating the MGS instead of the sires.

PMID- 19389976
TI  - Effects of breed and production system on lameness parameters in dairy cattle.
AB  - The aim of the present study was to assess the effects of Holstein-Friesian (HF)
      and Norwegian (N) dairy cattle genotypes on lameness parameters in dairy cattle
      within different production systems over the first 2 lactations. Following
      calving, HF (n = 39) and N (n = 45) heifers were allocated to 1 of 3 systems of
      production (high level of concentrate, low level of concentrate, and grass
      based). High- and low-concentrate animals were continuously housed indoors on a
      rotational system so that they spent similar amounts of time on slatted and solid
      concrete floors. Animals on the grass treatment grazed from spring to autumn in
      both years of the study, so that most animals on this treatment grazed from
      around peak to late lactation. Claw health was recorded in both hind claws of
      each animal at 4 observation periods during each lactation as follows: 1) -8 to
      70 d postcalving, 2) 71 to 150 d postcalving, 3) 151 to 225 d postcalving, and 4)
      226 to 364 d postcalving. Sole lesions, heel erosion, axial wall deviation, sole
      length of the right lateral hind claw (claw length), right heel width, and right
      lateral hind heel height were recorded as well as the presence of digital
      dermatitis. The N cows had lower (better) white line and total lesion scores than
      HF cows. Cows on the high- and low-concentrate treatments had better sole and
      total lesion scores than cows on the grass treatment. The HF cows had better
      locomotion scores than N cows. Breed and production system differences were
      observed with respect to claw conformation, including claw length, heel width,
      and heel height. Digital dermatitis was associated with worse sole lesion scores
      and interacted with production system to influence white line lesion scores and
      maximum heel erosion scores. This study shows that genetic, environmental, and
      infectious factors are associated with hoof pathologies in dairy cows.

PMID- 19389977
TI  - Estimation of economic values for traits of dairy sheep: I. Model development.
AB  - A bioeconomic model was developed to estimate effects of change in production and
      functional traits on profit of dairy or dual-purpose milked sheep under
      alternative management systems. The flock structure was described in terms of
      animal categories and probabilities of transitions among them, and a Markov chain
      approach was used to calculate the stationary state of the resultant ewe flock.
      The model included both deterministic and stochastic components. Performance for
      most traits was simulated as the population average, but variation in several
      traits was taken into account. Management options included lambing intervals,
      mating system, and culling strategy for ewes, weaning and marketing strategy for
      progeny, and feeding system. The present value of profit computed as the
      difference between total revenues and total costs per ewe per year, both
      discounted to the birth date of the animals, was used as the criterion for
      economic efficiency of the production system in the stationary state. Economic
      values (change in system profit per unit change in the trait) of up to 35 milk
      production, growth, carcass, wool, and functional traits may be estimated.

PMID- 19389978
TI  - Estimation of economic values for traits of dairy sheep: II. Model application to
      a production system with one lambing per year.
AB  - A bioeconomic model for dairy sheep was applied to a production system with one
      lambing per year. The classical extensive Carpathian system with indoor winter
      lambing, traditional weaning, sale of surplus lambs before Easter, and a summer
      milking period with ewes on pasture was modeled. The economic values of 15
      performance and functional traits were calculated for the Slovakian Improved
      Walachian multi-purpose breed. The economic values per unit increase in the
      traits were 0.32 euro/kg of milk yield during the standardized milking period of
      150 d, 0.29 euro/0.1% milk fat, 0.42 euro/0.1% milk protein, 0.28 euro/% and 0.56
      euro/% for conception rates of female lambs and ewes, respectively, 0.20
      euro/0.01 lamb born, 0.0036 euro/% and 0.0040 euro/% for lamb survival at birth
      and until weaning, respectively, 0.65 euro/kg of birth weight, 0.032 euro/g per d
      daily gain from birth until weaning, -0.030 euro/kg of mature weight, -0.38
      euro/0.1 and -0.21 euro/0.1 conformation quality grade for weaned lambs and adult
      sheep, respectively, 0.42 euro/kg of fleece weight and 11.10 euro/year of
      productive lifetime for ewes.

PMID- 19389979
TI  - Reaction norm model with unknown environmental covariate to analyze heterosis by
      environment interaction.
AB  - Crossbreeding is currently increasing in dairy cattle production. Several studies
      have shown an environment-dependent heterosis [i.e., an interaction between
      heterosis and environment (H x E)]. An H x E interaction is usually estimated
      from a few discrete environment levels. The present study proposes a reaction
      norm model to describe H x E interaction, which can deal with a large number of
      environment levels using few parameters. In the proposed model, total heterosis
      consists of an environment-independent part, which is described as a function of
      heterozygosity, and an environment-dependent part, which is described as a
      function of heterozygosity and environmental value (e.g., herd-year effect). A
      Bayesian approach is developed to estimate the environmental covariates, the
      regression coefficients of the reaction norm, and other parameters of the model
      simultaneously in both linear and nonlinear reaction norms. In the nonlinear
      reaction norm model, the H x E is approximated using linear splines. The approach
      was tested using simulated data, which were generated using an animal model with
      a reaction norm for heterosis. The simulation study includes 4 scenarios (the
      combinations of moderate vs. low heritability and moderate vs. low herd-year
      variation) of H x E interaction in a nonlinear form. In all scenarios, the
      proposed model predicted total heterosis very well. The correlation between true
      heterosis and predicted heterosis was 0.98 in the scenarios with low herd-year
      variation and 0.99 in the scenarios with moderate herd-year variation. This
      suggests that the proposed model and method could be a good approach to analyze H
      x E interactions and predict breeding values in situations in which heterosis
      changes gradually and continuously over an environmental gradient. On the other
      hand, it was found that a model ignoring H x E interaction did not significantly
      harm the prediction of breeding value under the simulated scenarios in which the
      variance for environment-dependent heterosis effects was small (as it generally
      is), and sires were randomly used over production environments.

PMID- 19389980
TI  - Marker-assisted selection can reduce true as well as pedigree-estimated
      inbreeding.
AB  - This study investigated whether selection using genotype information reduced the
      rate and level of true inbreeding, that is, identity by descent, at a selectively
      neutral locus as well as a locus under selection compared with traditional BLUP
      selection. In addition, the founder representation at these loci and the within
      family selection at the nonneutral locus were studied. The study was carried out
      using stochastic simulation of a population resembling the breeding nucleus of a
      dairy cattle population for 25 yr. Each year, 10 proven bulls were selected
      across herds along with 100 dams from within each of 40 herds. Selection was
      performed using BLUP, marker-assisted, or gene-assisted selection for a trait
      with low heritability (h2 = 0.04) only expressed in females, mimicking a health
      trait. The simulated genome consisted of 2 chromosomes. One biallelic
      quantitative trait loci (QTL) with an initial frequency of the favorable allele
      of 0.1, and initially explaining 25% of the genetic variance as well as 4 markers
      were simulated in linkage disequilibrium, all positioned at chromosome 1.
      Chromosome 2 was selectively neutral, and consisted of a single neutral locus.
      The results showed that in addition to reducing pedigree-estimated inbreeding,
      the incorporation of genotype information in the selection criteria also reduced
      the level and rate of true inbreeding. In general, true inbreeding in the QTL was
      greater than pedigree-estimated inbreeding with respect to both the level and
      rate of inbreeding, as expected. Also as expected, true and pedigree-estimated
      inbreeding in the neutral locus were the same. Furthermore, after 25 yr, or
      approximately 5 generations, the pedigree-estimated level of inbreeding was
      reduced by 11 and 24% compared with BLUP in gene- and marker-assisted selection,
      respectively, and the level of true inbreeding in the QTL was reduced by 22 and
      13%, respectively. The difference between selection scenarios was found to be
      caused by a larger number of founders being represented at the QTL when using
      genotype information in the selection criteria. This in turn was caused by an
      increased selection of individuals sharing the favorable QTL allele rather than
      individuals sharing genes on average, which was shown by a higher Mendelian
      selection differential in the QTL. Hence, even though the selection pressure was
      increased at the QTL, more variation was retained. The results suggest that
      marker-assisted selection is a useful selection strategy.

PMID- 19389981
TI  - Impact of genetic merit for milk somatic cell score of sires and maternal
      grandsires on herd life of their daughters.
AB  - A retrospective study of the impact of the estimated breeding values of sires and
      maternal grandsires for somatic cell score (SCS) on productive life (PL) of
      Holsteins and Jerseys was conducted. Data included records from 2,626,425
      Holstein and 142,725 Jersey cows. The sires and maternal grandsires of cows were
      required to have been available through artificial insemination and to have
      predicted transmitting ability (PTA) SCS evaluations based on 35 or more
      daughters. A weighted function (WPTA) of sire and maternal grandsire PTA for SCS
      was used: (sire PTA + 0.5 maternal grandsire PTA)/1.5. The 3 dependent variables
      were PL, frequency of cows culled for mastitis, and first-lactation SCS. The
      model included effects of herd, birth year, and WPTA (WPTA was categorized into
      groups: <2.70, 2.70 to 2.79, ..., 3.20 to 3.29, > or =3.30). For analysis of
      first-lactation SCS, calving year and calving month were substituted for birth
      year. Differences among WPTA groups were highly significant: as WPTA increased,
      PL decreased, whereas percentage culled for mastitis and first-lactation SCS
      increased. The range in PL from lowest to highest WPTA was 5.07 mo for Holsteins
      and 4.73 mo for Jerseys. Corresponding differences for percentage culled for
      mastitis were 7.0 and 5.6% and for SCS were 0.95 and 1.04 (for Holsteins and
      Jerseys, respectively). Although phenotypic studies suggest that cows with
      extremely low SCS were less resistant to mastitis, our results showed consistent
      improvements in PL, percentage culled for mastitis, and SCS of daughters when
      bulls were chosen for low PTA SCS.

PMID- 19389982
TI  - Genetic parameters of direct and maternal effects for calving ease in Dutch
      Holstein-Friesian cattle.
AB  - Genetic parameters of direct and maternal effects for calving ease in Dutch dairy
      cattle were estimated using 677,975 calving ease records from second calving.
      Particular emphasis was given to the presence and impact of environmental dam
      offspring covariances on the estimated direct-maternal genetic correlation.
      Moreover, a measure of heritability for traits affected by maternal effects was
      developed. In contrast to previous parameters, this parameter reflects the amount
      of genetic variance that can be used to generate a response to selection in
      maternally affected traits. Estimated genetic correlations between direct and
      maternal effects on calving ease have often been moderately negative,
      particularly in beef cattle. Environmental dam-offspring covariances have been
      put forward as an explanation for such estimates. We investigated the impact of
      environmental dam-offspring covariances by fitting correlated residuals between
      dam and offspring records in the statistical model, and by comparing results of a
      sire-maternal grandsire model with those of an animal model. Results show that
      calving ease in Dutch dairy cattle has a direct heritability of approximately
      0.08, a maternal heritability of approximately 0.04, a direct-maternal genetic
      correlation of approximately -0.20, and a total heritable variance equal to
      approximately 11% of phenotypic variance. Results of animal models and sire
      maternal grandsire models were very similar. The direct-maternal environmental
      covariance was near zero, and consequently had very little impact on the
      estimated genetic parameters. Transformation of observations to a liability scale
      did not affect the estimated genetic parameters and yielded a nearly identical
      ranking of sires.

PMID- 19389983
TI  - Single gene and gene interaction effects on fertilization and embryonic survival
      rates in cattle.
AB  - Decrease in fertility and conception rates is a major cause of economic loss and
      cow culling in dairy herds. Conception rate is the product of fertilization rate
      and embryonic survival rate. Identification of genetic factors that cause the
      death of embryos is the first step in eliminating this problem from the
      population and thereby increasing reproductive efficiency. A candidate pathway
      approach was used to identify candidate genes affecting fertilization and embryo
      survival rates using an in vitro fertilization experimental system. A total of
      7,413 in vitro fertilizations were performed using oocytes from 504 ovaries and
      semen samples from 10 different bulls. Fertilization rate was calculated as the
      number of cleaved embryos 48 h postfertilization out of the total number of
      oocytes exposed to sperm. Survival rate of embryos was calculated as the number
      of blastocysts on d 7 of development out of the number of total embryos cultured.
      All ovaries were genotyped for 8 genes in the POU1F1 signaling pathway. Single
      gene analysis revealed significant associations of GHR, PRLR, STAT5A, and UTMP
      with survival rate and of POU1F1, GHR, STAT5A, and OPN with fertilization rate.
      To further characterize the contribution of the entire integrated POU1F1 pathway
      to fertilization and early embryonic survival, a model selection procedure was
      applied. Comparisons among the different models showed that interactions between
      adjacent genes in the pathway revealed a significant contribution to the
      variation in fertility traits compared with other models that analyzed only bull
      information or only genes without interactions. Moreover, some genes that were
      not significant in the single-gene analysis showed significant effects in the
      interaction analysis. Thus, we propose that single genes as well as an entire
      pathway can be used in selection programs to improve reproduction performance in
      dairy cattle.

PMID- 19389984
TI  - Genetic evaluation of lactation persistency for five breeds of dairy cattle.
AB  - Cows with high lactation persistency tend to produce less milk than expected at
      the beginning of lactation and more than expected at the end. Best prediction of
      lactation persistency is calculated as a function of trait-specific standard
      lactation curves and linear regressions of test-day deviations on days in milk.
      Because regression coefficients are deviations from a tipping point selected to
      make yield and lactation persistency phenotypically uncorrelated it should be
      possible to use 305-d actual yield and lactation persistency to predict yield for
      lactations with later endpoints. The objectives of this study were to calculate
      (co)variance components and breeding values for best predictions of lactation
      persistency of milk (PM), fat (PF), protein (PP), and somatic cell score (PSCS)
      in breeds other than Holstein, and to demonstrate the calculation of prediction
      equations for 400-d actual milk yield. Data included lactations from Ayrshire,
      Brown Swiss, Guernsey (GU), Jersey (JE), and Milking Shorthorn (MS) cows calving
      since 1997. The number of sires evaluated ranged from 86 (MS) to 3,192 (JE), and
      mean sire estimated breeding value for PM ranged from 0.001 (Ayrshire) to 0.10
      (Brown Swiss); mean estimated breeding value for PSCS ranged from -0.01 (MS) to 
      0.043 (JE). Heritabilities were generally highest for PM (0.09 to 0.15) and
      lowest for PSCS (0.03 to 0.06), with PF and PP having intermediate values (0.07
      to 0.13). Repeatabilities varied considerably between breeds, ranging from 0.08
      (PSCS in GU, JE, and MS) to 0.28 (PM in GU). Genetic correlations of PM, PF, and
      PP with PSCS were moderate and favorable (negative), indicating that increasing
      lactation persistency of yield traits is associated with decreases in lactation
      persistency of SCS, as expected. Genetic correlations among yield and lactation
      persistency were low to moderate and ranged from -0.55 (PP in GU) to 0.40 (PP in
      MS). Prediction equations for 400-d milk yield were calculated for each breed by
      regression of both 305-d yield and 305-d yield and lactation persistency on 400-d
      yield. Goodness-of-fit was very good for both models, but the addition of
      lactation persistency to the model significantly improved fit in all cases.
      Routine genetic evaluations for lactation persistency, as well as the development
      of prediction equations for several lactation end-points, may provide producers
      with tools to better manage their herds.

PMID- 19389985
TI  - Genetic and environmental factors that affect gestation length in dairy cattle.
AB  - Genetic and environmental factors that might affect gestation length (GL) were
      investigated. Data included information from >11 million parturitions from 1999
      through 2006 for 7 US dairy breeds. Effects examined were year, herd-year, month,
      and age within parity of conception; parturition code (sex and multiple-birth
      status); lactation length and standardized milk yield of cow; service sire; cow
      sire; and cow. All effects were fixed except for service sire, cow sire, and cow.
      Mean GL for heifers and cows, respectively, were 277.8 and 279.4 d for Holsteins,
      278.4 and 280.0 d for Jerseys, 279.3 and 281.1 d for Milking Shorthorns, 281.6
      and 281.7 d for Ayrshires, 284.8 and 285.7 d for Guernseys, and 287.2 and 287.5 d
      for Brown Swiss. Estimated standard deviations of GL were greatly affected by
      data restrictions but generally were approximately 5 to 6 d. Year effects on GL
      were extremely small, but month effects were moderate. For Holstein cows, GL was
      2.0 d shorter for October conceptions than for January and February conceptions;
      4.7 and 5.6 d shorter for multiple births of the same sex than for single-birth
      females and males, respectively; 0.8 d longer for lactations of < or =250 d than
      for lactations of > or =501 d; and 0.6 d shorter for standardized yield of < or
      =8,000 kg than for yield of > or =14,001 kg. Estimates for GL heritability from
      parities 2 to 5 were 33 to 36% for service sire and 7 to 12% for cow sire;
      corresponding estimates from parity 1 were 46 to 47% and 10 to 12%. Estimates of
      genetic correlations between effects of service sire and cow sire on GL were 0.70
      to 0.85 for Brown Swiss, Holsteins, and Jerseys, which indicates that those
      traits likely are controlled by many of the same genes and can be used to
      evaluate each other. More accurate prediction of calving dates can help dairy
      producers to meet management requirements of pregnant animals and to administer
      better health care during high-risk phases of animals' lives. However,
      intentional selection for either shorter or longer GL is not recommended without
      consideration of its possible effect on other dependent traits (e.g., calving
      ease and stillbirth).

PMID- 19389986
TI  - Short communication: effect of preadjusting test-day yields for stage of
      pregnancy on variance component estimation in Canadian Ayrshires.
AB  - Preadjustment of phenotypic records is an alternative to accounting for the
      effect of pregnancy within the genetic evaluation model. Variance components used
      in the Canadian Test-Day Model may need to be re-estimated after preadjusting for
      pregnancy. The objective of this study was to assess the effect of preadjusting
      test-day yields on variance components and estimated breeding values using a
      random regression test-day model in a random sample of Ayrshire cows. A random
      sample of 981 Canadian Ayrshire cows from 18 complete herds (average of 54.5
      cows/herd) was analyzed. Two data sets were created using the same animals, one
      with unadjusted milk, fat, and protein yields, and one data set with test-day
      records adjusted for pregnancy effects. Pregnancy effect estimates from a
      previous study were used for additive preadjustment of records. Variance
      components were estimated using both data sets. Results were very similar between
      the 2 data sets for all estimated genetic parameters (heritabilities, genetic,
      and permanent environmental correlations). The relative squared differences were
      very small: 0.05% for heritabilities, 0.20% for genetic correlations, and 0.18%
      for permanent environmental correlations. Furthermore, paired Student's t-tests
      showed that the differences between the genetic parameters of data sets adjusted
      and unadjusted for pregnancy effect were not significantly different from 0.
      Results from this study show that preadjusting data for pregnancy did not yield
      changes in covariance component estimates, thus suggesting that preadjusting test
      day records could be a feasible solution to account for pregnancy in the Canadian
      Test-Day Model without changing the current model. Estimated breeding values
      (EBV) were calculated for both data sets to observe the impact of preadjusting
      for pregnancy. Overall, the largest changes in EBV seen when preadjusting for
      pregnancy (compared with unadjusted records) occurred for nonpregnant elite cows,
      whose EBV declined. Preadjusting for pregnancy before genetic evaluations
      improves the estimation of breeding values by adding the negative impact of
      pregnancy back onto pregnant cow test-day records, causing an increase in their
      production EBV.

PMID- 19389987
TI  - Algorithms for dairy barn design: maternity and milking areas.
AB  - This paper presents a series of algorithms for dairy barn design. The aim of the
      study was to develop algorithms for the design of new barn areas that can added
      to the main barn areas (resting, feeding, and exercise) to complement barn
      layout. More specifically, we developed design and dimensioning schemes to
      incorporate the maternity area and the milking area (holding pen and milking
      parlor) into dairy barns. Each algorithm requires input design parameters related
      to the characteristics of the areas considered. The output of the algorithms
      provides layout solutions for the maternity and milking areas and the overall
      dimensions of both areas, which enables the user to assess the possibility of
      incorporating maternity and milking into a dairy barn composed of resting,
      exercise, and feeding areas. The algorithms presented in this paper allow for
      space optimization by using the values defined for the design parameters
      considered.

PMID- 19389988
TI  - Laboratory evaluation of 3M Petrifilms and University of Minnesota Bi-plates as
      potential on-farm tests for clinical mastitis.
AB  - The objective was to determine test characteristics and compare 2 potential on
      farm culture systems for clinical mastitis, the Minnesota Easy Culture System II
      Bi-plate and Petrifilm. The tests were evaluated using clinically positive
      mastitic milk samples (n = 282) to determine their ability to differentiate
      appropriate treatment groups; all cases that had gram-positive growth were
      considered treatment candidates (n = 161), whereas cases that grew gram-negative
      organisms only or yielded no bacterial growth were classified as no treatment (n
      = 121). For Petrifilm, both undiluted and 1:10 diluted milk samples were used. To
      create treatment categories, 2 types of Petrifilms were used, Aerobic Count (AC)
      and Coliform Count (CC). Both Bi-plates and Petrifilms were read after 24 h of
      incubation. Analysis was conducted at various colony count thresholds for the
      Petrifilm test system. The combination of Petrifilms that had the highest
      sensitivity classified a case as gram-negative if there were > or =20 colonies
      present on the CC. If there were <20 colonies present on the CC and >5 colonies
      present on the AC, a case would be classified as gram-positive. The Bi-plate had
      a sensitivity of 97.9% and a specificity of 68.6%. The Petrifilm test system had
      a sensitivity of 93.8% and a specificity of 70.1%. There was no significant
      difference in the sensitivities between the tests. All Bi-plates and Petrifilms
      were read by a laboratory technician and a group of masked readers with limited
      microbiology training. Kappa values for the masked readers were 0.75 for Bi
      plates and 0.84 and 0.86 for AC and CC Petrifilms, respectively. The Bi-plate and
      Petrifilm were able to successfully categorize clinical cases of mastitis into 2
      treatments based on their ability to detect the presence of a gram-positive
      organism. Neither method had the ability to determine if a sample was
      contaminated. The results of this study indicate that both tests were able to
      appropriately categorize cases, which could potentially result in a reduction in
      the quantity of antibiotics used to treat clinical cases of mastitis.

PMID- 19389989
TI  - Mathematical optimization to improve cows' artificial insemination services.
AB  - Engineering tools and mathematical optimization are applied in this study to plan
      the work of the agents of the cow artificial insemination service (inseminator)
      in Israel. Time is crucial in insemination as the chances of conception decline
      with increasing delay between the start of estrus and insemination. About 1,090
      artificial inseminations of cows are performed daily in Israel. They involve 412
      farms in 283 villages, and are performed by 29 inseminators; the work plan should
      balance the work load among the inseminators. To this end, the working time of an
      inseminator in each village is required. Thus, a model to predict the working
      time in a village was developed. Subsequently, a mathematical optimization model
      was designed and solved, which aims to allocate customers to trips and to
      determine the itinerary of each trip to minimize total distance/time. The main
      benefits included a 21.4% reduction in total traveling time and a 55% reduction
      in the difference between the lengths of the longest and shortest working days.
      Moreover, the longest delay in reaching an estrous cow is reduced from 7.6 to 5.9
      h (i.e., by 1.7 h), which may increase the conception ratio by some 7%. In
      addition, the trade-off between work balance and total traveling time was
      studied.

PMID- 19389990
TI  - Feeding soyhulls to high-yielding dairy cows increased milk production, but not
      milking frequency, in an automatic milking system.
AB  - To attract a cow into an automatic milking system (AMS), a certain amount of
      concentrate pellets is provided while the cow is being milked. If the milking
      frequency in an AMS is increased, the intake of concentrate pellets might
      increase accordingly. Replacing conventional starchy pellets with nonstarchy
      pellets increased milk yield, milk fat, and milk protein and decreased body
      weight. The hypothesis was that a nonroughage by-product rich in digestible
      neutral detergent fiber, such as soyhulls and gluten feed, could replace starchy
      grain in pellets fed in an AMS. Sixty cows were paired by age, milk yield, and
      days in milk, and were fed a basic mixture ad libitum [16.2 +/- 0.35 (mean +/-
      SE) kg of dry matter intake/d per cow] plus a pelleted additive (6 to 14 kg of
      dry matter/d per cow) that was consumed in the AMS and in a concentrate self
      feeder, which could only be entered after passing through the AMS. The 2 feeding
      regimens differed only in the composition of the pelleted additives: the control
      group contained 52.9% starchy grain, whereas the experimental group contained 25%
      starchy grain, plus soyhulls and gluten feed as replacement for part of the
      grain. Wheat bran in the control ration, a source of fiber with low
      digestibility, was replaced with more digestible soyhulls and gluten. During the
      first 60 d in milk, a cow received 10 to 12 kg of concentrate pellets. After 60
      DIM, concentrate feed was allocated by milk production: < or =25 kg/d of milk
      entitled a cow to 2 kg/d of concentrate feed; >25 kg/d of milk entitled a cow to
      receive 1 kg/d of additional concentrate feed per 5 kg/d of additional milk
      production, and >60 kg/d of milk entitled a cow to receive 9 kg of concentrate.
      The concentrate feed was split between the AMS and concentrate self-feeder. The 2
      diets resulted in similar frequencies of voluntary milking (3.12 +/- 0.03 to 2.65
      +/- 0.03 visits/d per cow vs. 3.16 +/- 0.00 to 2.60 +/- 0.01 visits/d per cow).
      Average milk yields were higher in the experimental group (42.7 +/- 0.76 to 39.09
      +/- 0.33 kg/d per cow vs. 39.69 +/- 0.68 to 37.54 +/- 0.40 kg/d per cow) and
      percentages of milk protein (3.02 +/- 0.06 to 3.12 +/- 0.05% vs. 3.07 +/- 0.04 to
      3.20 +/- 0.04%) and milk fat (3.42 +/- 0.17 to 3.44 +/- 0.08% vs. 3.38 +/- 0.13
      to 3.55 +/- 0.06%) were similar in the 2 groups. The results suggest that the
      proposed pellets high in digestible neutral detergent fiber can be allocated via
      the AMS to selected high-yielding cows without a negative effect on appetite,
      milk yield, or milk composition while maintaining a high milking frequency.

PMID- 19389991
TI  - Ammonia emissions from dairy production in Wisconsin.
AB  - Ammonia gas is the only significant basic gas that neutralizes atmospheric acid
      gases produced from combustion of fossil fuels. This reaction produces an aerosol
      that is a component of atmospheric haze, is implicated in nitrogen (N)
      deposition, and may be a potential human health hazard. Because of the potential
      impact of NH3 emissions, environmentally and economically, the objective of this
      study was to obtain representative and accurate NH3 emissions data from large
      dairy farms (>800 cows) in Wisconsin. Ammonia concentrations and climatic
      measurements were made on 3 dairy farms during winter, summer, and autumn to
      calculate emissions using an inverse-dispersion analysis technique. These study
      farms were confinement systems utilizing freestall housing with nearby sand
      separators and lagoons for waste management. Emissions were calculated from the
      whole farm including the barns and any waste management components (lagoons and
      sand separators), and from these components alone when possible. During winter,
      the lagoons' NH3 emissions were very low and not measurable. During autumn and
      summer, whole-farm emissions were significantly larger than during winter, with
      about two-thirds of the total emissions originating from the waste management
      systems. The mean whole-farm NH3 emissions in winter, autumn, and summer were
      1.5, 7.5, and 13.7% of feed N inputs emitted as NH3-N, respectively. Average
      annual emission comparisons on a unit basis between the 3 farms were similar at
      7.0, 7.5, and 8.4% of input feed N emitted as NH3-N, with an annual average for
      all 3 farms of 7.6 +/- 1.5%. These winter, summer, autumn, and average annual NH3
      emissions are considerably smaller than currently used estimates for dairy farms,
      and smaller than emissions from other types of animal-feeding operations.

PMID- 19389992
TI  - International genetic evaluation for direct longevity in dairy bulls.
AB  - The aims of this study were to document, present, and discuss the procedure used
      to calculate the international estimated breeding value (EBV) for longevity for
      Brown Swiss, Guernsey, Holstein, Jersey, Red Dairy Cattle, and Simmental breeds.
      Data from 19 countries and 123,833 national sires' breeding value were used for
      this purpose. Trait definitions and national genetic evaluation procedures were
      first summarized; and this showed that differences among countries existed.
      International breeding values for direct longevity were calculated using a multi
      trait across-country evaluation model. The data editing method was identical to
      the one used for the February 2007 routine international genetic evaluation.
      Estimated genetic correlations presented in this study were similar to those
      presented in the literature and, in general, differed from unity because of
      differences in trait definitions, culling reasons, data included, evaluation
      procedures, genotype-environment interactions, and weak genetic ties among
      countries. The average genetic correlations for Holstein ranged from 0.49 to
      0.76. The genetic correlations for Brown Swiss and Guernsey ranged from 0.29 to
      0.95 and from 0.30 to 0.89, respectively. For Jersey and Red Dairy Cattle the
      genetic correlations ranged from 0.39 to 0.61 and from 0.30 to 0.96,
      respectively. For Simmental the genetic correlation was 0.59. Different
      predictors were used at national levels to define combined longevity. These
      predictors were combined using economic and empirical weights. Three out of 15
      countries published international EBV of direct longevity only and 12 out of 15
      countries combined direct longevity with predictors (combined longevity).
      International breeding values for longevity were combined into the total merit
      index by most of the member organizations and made available to breeders across
      the world through magazines and Web sites. Even if some breeders are not familiar
      with longevity EBV, they will select for this trait automatically if they use the
      published total merit indexes.

PMID- 19389993
TI  - Alternatives for examining daughter performance of progeny-test bulls between
      official evaluations.
AB  - In August 2007, the USDA changed from calculating official genetic evaluations
      quarterly to triannually in conjunction with the schedule change for
      international evaluations. To offset part of the delay in providing genetic
      information because of the reduced frequency of official evaluations, industry
      cooperators requested that interim evaluations be initiated for progeny-test (PT)
      bulls based on first-lactation records from PT daughters and their contemporaries
      that calved recently in cooperator herds. Alternatives for interim evaluations
      were studied to determine which would characterize genetic merit of PT bulls most
      accurately. Four alternative Holstein data sources were examined based on maximum
      data interval (most recent 12 or 18 mo of first calvings) and minimum number of
      PT daughters in herd (> or =1 or > or = 5). The highest correlation between
      August 2006 interim and official evaluations for milk yield was 0.980 for interim
      evaluations based on the most recent 18 mo of first calvings from cooperator
      herds with > or =1 PT daughter. That high correlation confirmed that interim
      evaluations based on limited data could provide genetic estimates of value
      between official evaluations. With the support of the Council on Dairy Cattle
      Breeding, the USDA initiated 3 interim evaluations each year with release limited
      to PT bulls with > or =10 daughters and an increase in reliability since the most
      recent official evaluation.

PMID- 19389994
TI  - History of aromatase: saga of an important biological mediator and therapeutic
      target.
AB  - Aromatase is the enzyme that catalyzes the conversion of androgens to estrogens.
      Initial studies of its enzymatic activity and function took place in an
      environment focused on estrogen as a component of the birth control pill. At an
      early stage, investigators recognized that inhibition of this enzyme could have
      major practical applications for treatment of hormone-dependent breast cancer,
      alterations of ovarian and endometrial function, and treatment of benign
      disorders such as gynecomastia. Two general approaches ultimately led to the
      development of potent and selective aromatase inhibitors. One targeted the enzyme
      using analogs of natural steroidal substrates to work out the relationships
      between structure and function. The other approach initially sought to block
      adrenal function as a treatment for breast cancer but led to the serendipitous
      finding that a nonsteroidal P450 steroidogenesis inhibitor, aminoglutethimide,
      served as a potent but nonselective aromatase inhibitor. Proof of the therapeutic
      concept of aromatase inhibition involved a variety of studies with
      aminoglutethimide and the selective steroidal inhibitor, formestane. The
      requirement for even more potent and selective inhibitors led to intensive
      molecular studies to identify the structure of aromatase, to development of high
      sensitivity estrogen assays, and to "mega" clinical trials of the third
      generation aromatase inhibitors, letrozole, anastrozole, and exemestane, which
      are now in clinical use in breast cancer. During these studies, unexpected
      findings led investigators to appreciate the important role of estrogens in males
      as well as in females and in multiple organs, particularly the bone and brain.
      These studies identified the important regulatory properties of aromatase acting
      in an autocrine, paracrine, intracrine, neurocrine, and juxtacrine fashion and
      the organ-specific enhancers and promoters controlling its transcription. The
      saga of these studies of aromatase and the ultimate utilization of inhibitors as
      highly effective treatments of breast cancer and for use in reproductive
      disorders serves as the basis for this first Endocrine Reviews history
      manuscript.

PMID- 19389997
TI  - Magnetic field sensing beyond the standard quantum limit using 10-spin NOON
      states.
AB  - Quantum entangled states can be very delicate and easily perturbed by their
      external environment. This sensitivity can be harnessed in measurement technology
      to create a quantum sensor with a capability of outperforming conventional
      devices at a fundamental level. We compared the magnetic field sensitivity of a
      classical (unentangled) system with that of a 10-qubit entangled state, realized
      by nuclei in a highly symmetric molecule. We observed a 9.4-fold quantum
      enhancement in the sensitivity to an applied field for the entangled system and
      show that this spin-based approach can scale favorably as compared with
      approaches in which qubit loss is prevalent. This result demonstrates a method
      for practical quantum field sensing technology.

PMID- 19389996
TI  - Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1
      and RanGTP.
AB  - CRM1 mediates nuclear export of numerous unrelated cargoes, which may carry a
      short leucine-rich nuclear export signal or export signatures that include folded
      domains. How CRM1 recognizes such a variety of cargoes has been unknown up to
      this point. Here we present the crystal structure of the SPN1.CRM1.RanGTP export
      complex at 2.5 angstrom resolution (where SPN1 is snurportin1 and RanGTP is
      guanosine 5' triphosphate-bound Ran). SPN1 is a nuclear import adapter for
      cytoplasmically assembled, m(3)G-capped spliceosomal U snRNPs (small nuclear
      ribonucleoproteins). The structure shows how CRM1 can specifically return the
      cargo-free form of SPN1 to the cytoplasm. The extensive contact area includes
      five hydrophobic residues at the SPN1 amino terminus that dock into a hydrophobic
      cleft of CRM1, as well as numerous hydrophilic contacts of CRM1 to m(3)G cap
      binding domain and carboxyl-terminal residues of SPN1. The structure suggests
      that RanGTP promotes cargo-binding to CRM1 solely through long-range
      conformational changes in the exportin.

PMID- 19389998
TI  - Entropic evidence for linguistic structure in the Indus script.
AB  - The script of the ancient Indus civilization remains undeciphered. The hypothesis
      that the script encodes language has recently been questioned. Here, we present
      evidence for the linguistic hypothesis by showing that the script's conditional
      entropy is closer to those of natural languages than various types of
      nonlinguistic systems.

PMID- 19389995
TI  - Stem cells to pancreatic beta-cells: new sources for diabetes cell therapy.
AB  - The number of patients worldwide suffering from the chronic disease diabetes
      mellitus is growing at an alarming rate. Insulin-secreting beta-cells in the
      islet of Langerhans are damaged to different extents in diabetic patients, either
      through an autoimmune reaction present in type 1 diabetic patients or through
      inherent changes within beta-cells that affect their function in patients
      suffering from type 2 diabetes. Cell replacement strategies via islet
      transplantation offer potential therapeutic options for diabetic patients.
      However, the discrepancy between the limited number of donor islets and the high
      number of patients who could benefit from such a treatment reflects the dire need
      for renewable sources of high-quality beta-cells. Human embryonic stem cells
      (hESCs) are capable of self-renewal and can differentiate into components of all
      three germ layers, including all pancreatic lineages. The ability to
      differentiate hESCs into beta-cells highlights a promising strategy to meet the
      shortage of beta-cells. Here, we review the different approaches that have been
      used to direct differentiation of hESCs into pancreatic and beta-cells. We will
      focus on recent progress in the understanding of signaling pathways and
      transcription factors during embryonic pancreas development and how this
      knowledge has helped to improve the methodology for high-efficiency beta-cell
      differentiation in vitro.

PMID- 19389999
TI  - Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning.
AB  - Natural rewards and drugs of abuse can alter dopamine signaling, and ventral
      tegmental area (VTA) dopaminergic neurons are known to fire action potentials
      tonically or phasically under different behavioral conditions. However, without
      technology to control specific neurons with appropriate temporal precision in
      freely behaving mammals, the causal role of these action potential patterns in
      driving behavioral changes has been unclear. We used optogenetic tools to
      selectively stimulate VTA dopaminergic neuron action potential firing in freely
      behaving mammals. We found that phasic activation of these neurons was sufficient
      to drive behavioral conditioning and elicited dopamine transients with magnitudes
      not achieved by longer, lower-frequency spiking. These results demonstrate that
      phasic dopaminergic activity is sufficient to mediate mammalian behavioral
      conditioning.

PMID- 19390000
TI  - Penultimate deglacial sea-level timing from uranium/thorium dating of Tahitian
      corals.
AB  - The timing of sea-level change provides important constraints on the mechanisms
      driving Earth's climate between glacial and interglacial states. Fossil corals
      constrain the timing of past sea level by their suitability for dating and their
      growth position close to sea level. The coral-derived age for the last
      deglaciation is consistent with climate change forced by Northern Hemisphere
      summer insolation (NHI), but the timing of the penultimate deglaciation is more
      controversial. We found, by means of uranium/thorium dating of fossil corals,
      that sea level during the penultimate deglaciation had risen to ~85 meters below
      the present sea level by 137,000 years ago, and that it fluctuated on a
      millennial time scale during deglaciation. This indicates that the penultimate
      deglaciation occurred earlier with respect to NHI than the last deglacial,
      beginning when NHI was at a minimum.

PMID- 19390001
TI  - Effect of a peripheral nerve block on torque produced by repetitive electrical
      stimulation.
AB  - Neuromuscular electrical stimulation (NMES) generates contractions by activation
      of motor axons (peripheral mechanism), but the afferent volley also contributes
      by recruiting spinal motoneurons synaptically (central mechanism), which recruits
      motoneurons according to Henneman's size principle. Thus, we hypothesized that
      contractions that develop due to a combination of peripheral and central
      mechanisms will fatigue less rapidly than when electrically evoked contractions
      are generated by the activation of motor axons alone. Plantar-flexion torque
      evoked by NMES over the triceps surae was compared in five able-bodied subjects
      before (Intact) and during (Blocked) a complete anesthetic block of the tibial
      and common peroneal nerves. In the Blocked condition, plantar-flexion torque
      could only develop from the direct activation of motor axons beneath the
      stimulating electrodes. NMES was delivered using three protocols: protocol A,
      constant 100 Hz for 30 s; protocol B, four 2-s bursts of 100 Hz alternating with
      20-Hz stimulation; and protocol C, alternating 100 Hz bursts (1 s on, 1 s off)
      for 30 s. The percent change in evoked plantar flexion torque from the beginning
      to the end of the stimulation differed (P < 0.05) between Intact and Blocked
      conditions for all protocols (Intact: protocol A = +125%, B = +230%, C = +78%;
      Blocked: protocol A = -79%, B = -15%, C = -35%). These results corroborate
      previous evidence that NMES can evoke contractions via the recruitment of spinal
      motoneurons in addition to the direct recruitment of motor axons. We now show
      that NMES delivered for periods of up to 30 s generates plantar-flexion torque
      which decreases when only motor axons are recruited and increases when the
      central nervous system can contribute.

PMID- 19390002
TI  - Artificial gravity maintains skeletal muscle protein synthesis during 21 days of
      simulated microgravity.
AB  - We sought to determine the effects of longitudinal loading (artificial gravity)
      on skeletal muscle protein kinetics in 15 healthy young males after 21 days of 6
      degrees head-down tilt bed rest [experimental treatment (Exp) group: n = 8, 31 +/
      1 yr; control (Con) group; n = 7, 28 +/- 1 yr, means +/- SE]. On days 1 and 21
      of bed rest, postabsorptive venous blood samples and muscle biopsies (vastus
      lateralis and soleus) were obtained during a 1-h pulse bolus infusion protocol (0
      min, l-[ring-(13)C(6)]phenylalanine, 35 mumol/kg; 30 min, l-[ring
      (15)N]phenylalanine, 35 mumol/kg). Outcome measures included mixed muscle
      fractional synthesis (FSR) and breakdown rates (FBR). The Exp group experienced 1
      h of longitudinal loading (2.5G at the feet) via a short-radius centrifuge during
      each day of bed rest. Mixed muscle FSR in the Con group was reduced by 48.5% (day
      1, 0.081 +/- 0.000%/h vs. day 21, 0.042 +/- 0.000%/h; P = 0.001) in vastus
      lateralis after 21 days of bed rest, whereas the Exp group maintained their rate
      of protein synthesis. A similar but nonsignificant change in FSR was noted for
      the soleus muscle (Exp, -7%; Con, -22%). No changes in muscle protein breakdown
      were observed. In conclusion, 1 h of daily exposure to artificial gravity
      maintained the rate of protein synthesis of the vastus lateralis and may
      represent an effective adjunct countermeasure to combat the loss of muscle mass
      and functional during extended spaceflight.

PMID- 19390003
TI  - Absence of caspase-3 protects against denervation-induced skeletal muscle
      atrophy.
AB  - The ubiquitin-proteasome system is a key proteolytic pathway activated during
      skeletal muscle atrophy. The proteasome, however, cannot degrade intact
      myofibrils or actinomyosin complexes. In rodent models of diabetes mellitus and
      uremia, caspase-3 is involved in actinomyosin cleavage, generating fragments that
      subsequently undergo ubiquitin-proteasome-mediated degradation. Here, we
      demonstrate that caspase-3 also mediates denervation-induced muscle atrophy. At 2
      wk after tibial nerve transection, the denervated gastrocnemius of caspase-3
      knockout mice weighed more and demonstrated larger fiber-type-specific cross
      sectional area than the denervated gastrocnemius of wild-type mice. However,
      there was no difference between caspase-3-knockout and wild-type denervated
      muscles in the magnitude or pattern of actinomyosin degradation, as determined by
      Western blotting for actin and the 14-kDa actin fragment. Similarly, there was no
      difference between caspase-3-knockout and wild-type denervated muscles in the
      magnitude of increase in proteasome activity, total protein ubiquitination, or
      atrogin-1 and muscle-specific ring finger protein 1 transcript levels. In
      contrast, there was an increase in TdT-mediated dUTP nick end label-positive
      nuclei in the denervated muscle of wild-type compared with caspase-3-knockout
      mice. Apoptotic signaling upstream of caspase-3 remained intact, with equivalent
      mitochondrial Bax translocation and cytochrome c release and caspase-9 activation
      in the denervated gastrocnemius muscle of wild-type and caspase-3-knockout mice.
      In contrast, diminished poly(ADP-ribose) polymerase cleavage in the denervated
      muscle of caspase-3-knockout compared with wild-type mice revealed that apoptotic
      signaling downstream of caspase-3 was impaired, suggesting that the absence of
      caspase-3 protects against denervation-induced muscle atrophy by suppressing
      apoptosis as opposed to ubiquitin-proteasome-mediated protein degradation.

PMID- 19390004
TI  - Respiratory muscle function and activation in chronic obstructive pulmonary
      disease.
AB  - Inspiratory muscles are uniquely adapted for endurance, but their function is
      compromised in chronic obstructive pulmonary disease (COPD) due to increased
      loads, reduced mechanical advantage, and increased ventilatory requirements. The
      hyperinflation of COPD reduces the flow and pressure-generating capacity of the
      diaphragm. This is compensated by a threefold increase in neural drive,
      adaptations of the chest wall and diaphragm shape to accommodate the increased
      volume, and adaptations of muscle fibers to preserve strength and increase
      endurance. Paradoxical indrawing of the lower costal margin during inspiration in
      severe COPD (Hoover's sign) correlates with high inspiratory drive and severe
      airflow obstruction rather than contraction of radially oriented diaphragm
      fibers. The inspiratory muscles remain highly resistant to fatigue in patients
      with COPD, and the ultimate development of ventilatory failure is associated with
      insufficient central drive. Sleep is associated with reduced respiratory drive
      and impairments of lung and chest wall function, which are exaggerated in COPD
      patients. Profound hypoxemia and hypercapnia can occur in rapid eye movement
      sleep and contribute to the development of cor pulmonale. Inspiratory muscles
      adapt to chronic loading with an increased proportion of slow, fatigue-resistant
      fiber types, increased oxidative capacity, and reduced fiber cross-sectional
      area, but the capacity of the diaphragm to increase ventilation in exercise is
      compromised in COPD. In COPD, neural drive to the diaphragm increases to near
      maximal levels in exercise, but it does not develop peripheral muscle fatigue.
      The improvement in exercise capacity and dyspnea following lung volume reduction
      surgery is associated with a substantial reduction in neural drive to the
      inspiratory muscles.

PMID- 19390006
TI  - How to keep science moving.

PMID- 19390007
TI  - Biomedical policy. Draft stem cell guidelines please many, disappoint some.

PMID- 19390005
TI  - Motor unit control and force fluctuation during fatigue.
AB  - During isometric contractions, the fluctuation of the force output of muscles
      increases as the muscle fatigues, and the contraction is sustained to exhaustion.
      We analyzed motor unit firing data from the vastus lateralis muscle to
      investigate which motor unit control parameters were associated with the
      increased force fluctuation. Subjects performed a sequence of isometric constant
      force contractions sustained at 20% maximal force, each spaced by a 6-s rest
      period. The contractions were performed until the mean value of the force output
      could not be maintained at the desired level. Intramuscular EMG signals were
      detected with a quadrifilar fine-wire sensor. The EMG signals were decomposed to
      identify all of the firings of several motor units by using an artificial
      intelligence-based set of algorithms. We were able to follow the behavior of the
      same motor units as the endurance time progressed. The force output of the muscle
      was filtered to remove contributions from the tracking task. The coefficient of
      variation of the force was found to increase with endurance time (P < 0.001, R(2)
      = 0.51). We calculated the coefficient of variation of the firing rates, the
      synchronization of pairs of motor unit firings, the cross-correlation value of
      the firing rates of pairs of motor units, the cross-correlation of the firing
      rates of motor units and the force, and the number of motor units recruited
      during the contractions. Of these parameters, only the cross-correlation of the
      firing rates (P < 0.01, R(2) = 0.10) and the number of recruited motor units (P =
      0.042, R(2) = 0.22) increased significantly with endurance time for grouped
      subjects. A significant increase (P < 0.001, R(2) = 0.16) in the cross
      correlation of the firing rates and force was also observed. It is suggested that
      the increase in the cross-correlation of the firing rates is likely due to a
      decrease in the sensitivity of the proprioceptive feedback from the spindles.

PMID- 19390008
TI  - Archaeology. Did humans learn from hobbits?

PMID- 19390009
TI  - Biomedical research. Genome scans: impatient for the payoff.

PMID- 19390011
TI  - Newsmaker interview. Brilliant moves to tackle global threats. Interview by Greg
      Miller.

PMID- 19390014
TI  - German Physical Society. Leverage: the root of all financial turmoil.

PMID- 19390012
TI  - Scientific misconduct. Science retracts discredited paper; bitter patent dispute
      continues.

PMID- 19390015
TI  - German Physical Society. A new take on doping in iron-based superconductors.

PMID- 19390016
TI  - German Physical Society. Water droplets grow faster than expected.

PMID- 19390017
TI  - German Physical Society. Snapshots from the meeting.

PMID- 19390018
TI  - Archaeology. A new look at the Mayas' end.

PMID- 19390019
TI  - Newsmaker interview. Jim Kim on why he took the top job at Dartmouth. Interview
      by Jon Cohen.

PMID- 19390020
TI  - Neuroscience. A quest for compassion.

PMID- 19390021
TI  - Astronomy. Stars in dusty filing cabinets.

PMID- 19390022
TI  - The way forward in the world of robotics.

PMID- 19390023
TI  - The hard problem.

PMID- 19390024
TI  - Opportunity in the wake of natural "disasters".

PMID- 19390025
TI  - Retraction.

PMID- 19390026
TI  - Linguistics more robust than genetics.

PMID- 19390027
TI  - Culling whales: ethically and ecologically wrong.

PMID- 19390029
TI  - Comment on "Colossal ionic conductivity at interfaces of epitaxial
      ZrO2:Y2O3/SrTiO3 heterostructures".
AB  - Garcia-Barriocanal et al. (Reports, 1 August 2008, p. 676) reported colossal
      conductivity enhancements in yttria-stabilized zirconia (YSZ)/strontium titanate
      (STO) epitaxial heterostructures and claimed that the conductivity was ionic. I
      argue that the claimed ionic conductivity lacks experimental support and that the
      observed conductivity enhancement is most probably due to the p-type conductivity
      of STO.

PMID- 19390030
TI  - Research priorities. Farm animal research in crisis.

PMID- 19390031
TI  - Professional development. Summer institute to improve university science
      teaching.

PMID- 19390032
TI  - Plant science. Exploring terra incognita.

PMID- 19390033
TI  - Physics. Where is my quantum computer?

PMID- 19390034
TI  - Geophysics. The thickness of tectonic plates.

PMID- 19390035
TI  - Cell signaling. To divide or not to divide.

PMID- 19390036
TI  - Atmospheric science. Shifting gear, quickly.

PMID- 19390037
TI  - Genetics. It's a bull's market.

PMID- 19390038
TI  - Fire in the Earth system.
AB  - Fire is a worldwide phenomenon that appears in the geological record soon after
      the appearance of terrestrial plants. Fire influences global ecosystem patterns
      and processes, including vegetation distribution and structure, the carbon cycle,
      and climate. Although humans and fire have always coexisted, our capacity to
      manage fire remains imperfect and may become more difficult in the future as
      climate change alters fire regimes. This risk is difficult to assess, however,
      because fires are still poorly represented in global models. Here, we discuss
      some of the most important issues involved in developing a better understanding
      of the role of fire in the Earth system.

PMID- 19390039
TI  - Coat color variation at the beginning of horse domestication.
AB  - The transformation of wild animals into domestic ones available for human
      nutrition was a key prerequisite for modern human societies. However, no other
      domestic species has had such a substantial impact on the warfare,
      transportation, and communication capabilities of human societies as the horse.
      Here, we show that the analysis of ancient DNA targeting nuclear genes
      responsible for coat coloration allows us to shed light on the timing and place
      of horse domestication. We conclude that it is unlikely that horse domestication
      substantially predates the occurrence of coat color variation, which was found to
      begin around the third millennium before the common era.

PMID- 19390040
TI  - Greatly increased toughness of infiltrated spider silk.
AB  - In nature, tiny amounts of inorganic impurities, such as metals, are incorporated
      in the protein structures of some biomaterials and lead to unusual mechanical
      properties of those materials. A desire to produce these biomimicking new
      materials has stimulated materials scientists, and diverse approaches have been
      attempted. In contrast, research to improve the mechanical properties of
      biomaterials themselves by direct metal incorporation into inner protein
      structures has rarely been tried because of the difficulty of developing a method
      that can infiltrate metals into biomaterials, resulting in a metal-incorporated
      protein matrix. We demonstrated that metals can be intentionally infiltrated into
      inner protein structures of biomaterials through multiple pulsed vapor-phase
      infiltration performed with equipment conventionally used for atomic layer
      deposition (ALD). We infiltrated zinc (Zn), titanium (Ti), or aluminum (Al),
      combined with water from corresponding ALD precursors, into spider dragline silks
      and observed greatly improved toughness of the resulting silks. The presence of
      the infiltrated metals such as Al or Ti was verified by energy-dispersive x-ray
      (EDX) and nuclear magnetic resonance spectra measured inside the treated silks.
      This result of enhanced toughness of spider silk could potentially serve as a
      model for a more general approach to enhance the strength and toughness of other
      biomaterials.

PMID- 19390041
TI  - A global view of the lithosphere-asthenosphere boundary.
AB  - The lithosphere-asthenosphere boundary divides the rigid lid from the weaker
      mantle and is fundamental in plate tectonics. However, its depth and defining
      mechanism are not well known. We analyzed 15 years of global seismic data using P
      to-S (Ps) converted phases and imaged an interface that correlates with tectonic
      environment, varying from 95 +/- 4 kilometers beneath Precambrian shields and
      platforms to 81 +/- 2 kilometers beneath tectonically altered regions and 70 +/-
      4 kilometers at oceanic island stations. High-frequency Ps observations require a
      sharp discontinuity; therefore, this interface likely represents a boundary in
      composition, melting, or anisotropy, not temperature alone. It likely represents
      the lithosphere-asthenosphere boundary under oceans and tectonically altered
      regions, but it may constitute another boundary in cratonic regions where the
      lithosphere-asthenosphere boundary is thought to be much deeper.

PMID- 19390042
TI  - Seismic evidence for sharp lithosphere-asthenosphere boundaries of oceanic
      plates.
AB  - The mobility of the lithosphere over a weaker asthenosphere constitutes the
      essential element of plate tectonics, and thus the understanding of the processes
      at the lithosphere-asthenosphere boundary (LAB) is fundamental to understand how
      our planet works. It is especially so for oceanic plates because their relatively
      simple creation and evolution should enable easy elucidation of the LAB. Data
      from borehole broadband ocean bottom seismometers show that the LAB beneath the
      Pacific and Philippine Sea plates is sharp and age-dependent. The observed large
      shear wave velocity reduction at the LAB requires a partially molten
      asthenosphere consisting of horizontal melt-rich layers embedded in meltless
      mantle, which accounts for the large viscosity contrast at the LAB that
      facilitates horizontal plate motions.

PMID- 19390043
TI  - Subducting slab ultra-slow velocity layer coincident with silent earthquakes in
      southern Mexico.
AB  - Great earthquakes have repeatedly occurred on the plate interface in a few
      shallow-dipping subduction zones where the subducting and overriding plates are
      strongly locked. Silent earthquakes (or slow slip events) were recently
      discovered at the down-dip extension of the locked zone and interact with the
      earthquake cycle. Here, we show that locally observed converted SP arrivals and
      teleseismic underside reflections that sample the top of the subducting plate in
      southern Mexico reveal that the ultra-slow velocity layer (USL) varies spatially
      (3 to 5 kilometers, with an S-wave velocity of approximately 2.0 to 2.7
      kilometers per second). Most slow slip patches coincide with the presence of the
      USL, and they are bounded by the absence of the USL. The extent of the USL
      delineates the zone of transitional frictional behavior.

PMID- 19390044
TI  - 14CH4 measurements in Greenland ice: investigating last glacial termination CH4
      sources.
AB  - The cause of a large increase of atmospheric methane concentration during the
      Younger Dryas-Preboreal abrupt climatic transition (approximately 11,600 years
      ago) has been the subject of much debate. The carbon-14 (14C) content of methane
      (14CH4) should distinguish between wetland and clathrate contributions to this
      increase. We present measurements of 14CH4 in glacial ice, targeting this
      transition, performed by using ice samples obtained from an ablation site in west
      Greenland. Measured 14CH4 values were higher than predicted under any scenario.
      Sample 14CH4 appears to be elevated by direct cosmogenic 14C production in ice.
      14C of CO was measured to better understand this process and correct the sample
      14CH4. Corrected results suggest that wetland sources were likely responsible for
      the majority of the Younger Dryas-Preboreal CH4 rise.

PMID- 19390045
TI  - Tuning the activation threshold of a kinase network by nested feedback loops.
AB  - Determining proper responsiveness to incoming signals is fundamental to all
      biological systems. We demonstrate that intracellular signaling nodes can tune a
      signaling network's response threshold away from the basal median effective
      concentration established by ligand-receptor interactions. Focusing on the
      bistable kinase network that governs progesterone-induced meiotic entry in
      Xenopus oocytes, we characterized glycogen synthase kinase-3beta (GSK-3beta) as a
      dampener of progesterone responsiveness. GSK-3beta engages the meiotic kinase
      network through a double-negative feedback loop; this specific feedback
      architecture raises the progesterone threshold in correspondence with the
      strength of double-negative signaling. We also identified a marker of nutritional
      status, l-leucine, which lowers the progesterone threshold, indicating that
      oocytes integrate additional signals into their cell-fate decisions by modulating
      progesterone responsiveness.

PMID- 19390046
TI  - Catalytic core of a membrane-associated eukaryotic polyphosphate polymerase.
AB  - Polyphosphate (polyP) occurs ubiquitously in cells, but its functions are poorly
      understood and its synthesis has only been characterized in bacteria. Using x-ray
      crystallography, we identified a eukaryotic polyphosphate polymerase within the
      membrane-integral vacuolar transporter chaperone (VTC) complex. A 2.6 angstrom
      crystal structure of the catalytic domain grown in the presence of adenosine
      triphosphate (ATP) reveals polyP winding through a tunnel-shaped pocket.
      Nucleotide- and phosphate-bound structures suggest that the enzyme functions by
      metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line
      transferred to an acceptor phosphate to form polyP chains. Mutational analysis of
      the transmembrane domain indicates that VTC may integrate cytoplasmic polymer
      synthesis with polyP membrane translocation. Identification of the polyP
      synthesizing enzyme opens the way to determine the functions of polyP in lower
      eukaryotes.

PMID- 19390047
TI  - Homeostatic sleep pressure and responses to sustained attention in the
      suprachiasmatic area.
AB  - Throughout the day, cognitive performance is under the combined influence of
      circadian processes and homeostatic sleep pressure. Some people perform best in
      the morning, whereas others are more alert in the evening. These chronotypes
      provide a unique way to study the effects of sleep-wake regulation on the
      cerebral mechanisms supporting cognition. Using functional magnetic resonance
      imaging in extreme chronotypes, we found that maintaining attention in the
      evening was associated with higher activity in evening than morning chronotypes
      in a region of the locus coeruleus and in a suprachiasmatic area (SCA) including
      the circadian master clock. Activity in the SCA decreased with increasing
      homeostatic sleep pressure. This result shows the direct influence of the
      homeostatic and circadian interaction on the neural activity underpinning human
      behavior.

PMID- 19390048
TI  - Intuition and deliberation: two systems for strategizing in the brain.
AB  - Dual-process theories distinguish between intuition (fast and emotional) and
      reasoning (slow and controlled) as a basis for human decision-making. We contrast
      dominance-solvable games, which can be solved by step-by-step deliberative
      reasoning, with pure coordination games, which must be solved intuitively. Using
      functional magnetic resonance imaging, we found that the middle frontal gyrus,
      the inferior parietal lobule, and the precuneus were more active in dominance
      solvable games than in coordination games. The insula and anterior cingulate
      cortex showed the opposite pattern. Moreover, precuneus activity correlates
      positively with how "effortful" a dominance-solvable game is, whereas insula
      activity correlates positively with how "effortless" a coordination game is.

PMID- 19390050
TI  - Genome-wide survey of SNP variation uncovers the genetic structure of cattle
      breeds.
AB  - The imprints of domestication and breed development on the genomes of livestock
      likely differ from those of companion animals. A deep draft sequence assembly of
      shotgun reads from a single Hereford female and comparative sequences sampled
      from six additional breeds were used to develop probes to interrogate 37,470
      single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and
      biologically diverse breeds. These data show that cattle have undergone a rapid
      recent decrease in effective population size from a very large ancestral
      population, possibly due to bottlenecks associated with domestication, selection,
      and breed formation. Domestication and artificial selection appear to have left
      detectable signatures of selection within the cattle genome, yet the current
      levels of diversity within breeds are at least as great as exists within humans.

PMID- 19390051
TI  - Revealing the history of sheep domestication using retrovirus integrations.
AB  - The domestication of livestock represented a crucial step in human history. By
      using endogenous retroviruses as genetic markers, we found that sheep
      differentiated on the basis of their "retrotype" and morphological traits
      dispersed across Eurasia and Africa via separate migratory episodes. Relicts of
      the first migrations include the Mouflon, as well as breeds previously recognized
      as "primitive" on the basis of their morphology, such as the Orkney, Soay, and
      the Nordic short-tailed sheep now confined to the periphery of northwest Europe.
      A later migratory episode, involving sheep with improved production traits,
      shaped the great majority of present-day breeds. The ability to differentiate
      genetically primitive sheep from more modern breeds provides valuable insights
      into the history of sheep domestication.

PMID- 19390053
TI  - Health literacy self-management by patients with type 2 diabetes and stage 3
      chronic kidney disease.
AB  - This is a qualitative study report from a parent study that used a concurrent
      mixed methods design whose aim was to describe the transition and self-management
      experiences of patients diagnosed with type 2 diabetes mellitus (T2DM) and stage
      3 chronic kidney disease (CKD). Six adult men and women recruited from outpatient
      clinics completed two focus group interviews. Discerned in the ethnographic
      analysis of interviews and field notes using ATLAS/ti was a pattern of Health
      Literacy Self-Management with two major threads: (a) transition experience to
      self-advocacy characterized as seeking useful resources and difficulties in
      resource use and (b) partnering with the health care provider (HCP) characterized
      as helpful messaging and messaging confusion. Self-management support includes a
      shared responsibility and developmental process by the patient and the HCP to
      achieve quality care. Description of behavioral factors and self-management
      processes provides a foundation for future study.

PMID- 19390054
TI  - PECAM-1 is necessary for flow-induced vascular remodeling.
AB  - OBJECTIVE: Vascular remodeling is a physiological process that occurs in response
      to long-term changes in hemodynamic conditions, but may also contribute to the
      pathophysiology of intima-media thickening (IMT) and vascular disease. Shear
      stress detection by the endothelium is thought to be an important determinant of
      vascular remodeling. Previous work showed that platelet endothelial cell adhesion
      molecule-1 (PECAM-1) is a component of a mechanosensory complex that mediates
      endothelial cell (EC) responses to shear stress. METHODS AND RESULTS: We tested
      the hypothesis that PECAM-1 contributes to vascular remodeling by analyzing the
      response to partial carotid artery ligation in PECAM-1 knockout mice and wild
      type littermates. PECAM-1 deficiency resulted in impaired vascular remodeling and
      significantly reduced IMT in areas of low flow. Inward remodeling was associated
      with PECAM-1-dependent NFkappaB activation, surface adhesion molecule expression,
      and leukocyte infiltration as well as Akt activation and vascular cell
      proliferation. CONCLUSIONS: PECAM-1 plays a crucial role in the activation of the
      NFkappaB and Akt pathways and inflammatory cell accumulation during vascular
      remodeling and IMT. Elucidation of some of the signals that drive vascular
      remodeling represent pharmacologically tractable targets for the treatment of
      restenosis after balloon angioplasty or stent placement.

PMID- 19390055
TI  - Disruption of SEMA4D ameliorates platelet hypersensitivity in dyslipidemia and
      confers protection against the development of atherosclerosis.
AB  - OBJECTIVE: In dyslipidemic states, platelets become hyperreactive, secreting
      molecules that promote atherosclerosis. We have shown that the semaphorin family
      member, sema4D (CD100), is expressed on the surface of platelets and proposed
      that its role includes promoting thrombus growth by binding to nearby platelets
      and endothelial cells, both of which express sema4D receptors. Here we tested the
      hypothesis that deleting sema4D will attenuate the adverse consequences of
      dyslipidemia on platelets and the vessel wall. METHODS AND RESULTS: Platelet
      function and atherosclerotic lesion formation were measured in LDLR(-/-) and
      sema4D(-/-)LDLR(-/-) mice after 6 months on a high-fat diet. All of the mice
      developed the dyslipidemia expected on this diet in the absence of functional LDL
      receptors. However, when compared to LDLR(-/-) mice, sema4D(-/-) LDLR(-/-) mice
      had reduced lipid deposition in the descending aorta, a 6-fold decrease in the
      frequency of arterial occlusion and a reduction to near wild-type levels in the
      accumulation of platelets after injury. These differences were retained ex vivo,
      with a marked decrease in platelet accumulation on collagen under flow and in
      platelet aggregation. CONCLUSIONS: These results show that loss of sema4D
      expression reduces the platelet hyperactivity otherwise found in dyslipidemia,
      and confers protection against the development of atherosclerosis.

PMID- 19390056
TI  - Interleukin-6 modulates the expression of the bone morphogenic protein receptor
      type II through a novel STAT3-microRNA cluster 17/92 pathway.
AB  - Dysregulated expression of bone morphogenetic protein receptor type II (BMPR2) is
      a pathogenetic hallmark of pulmonary hypertension. Downregulation of BMPR2
      protein but not mRNA has been observed in multiple animal models mimicking the
      disease, indicating a posttranscriptional mechanism of regulation. Because
      microRNAs (miRNAs) regulate gene expression mainly through inhibition of target
      gene translation, we hypothesized that miRNAs may play a role in the modulation
      of BMPR2. Performing a computational algorithm on the BMPR2 gene, several miRNAs
      encoded by the miRNA cluster 17/92 (miR-17/92) were retrieved as potential
      regulators. Ectopic overexpression of miR-17/92 resulted in a strong reduction of
      the BMPR2 protein, and a reporter gene system showed that BMPR2 is directly
      targeted by miR-17-5p and miR-20a. By stimulation experiments, we found that the
      miR-17/92 cluster is modulated by interleukin (IL)-6, a cytokine involved in the
      pathogenesis of pulmonary hypertension. Because IL-6 signaling is mainly mediated
      by STAT3 (signal transducer and activator of transcription 3), the expression of
      STAT3 was knocked down by small interfering RNA, which abolished the IL-6
      mediated expression of miR-17/92. Consistent with these data, we found a highly
      conserved STAT3-binding site in the promoter region of the miR-17/92 gene
      (C13orf25). Promoter studies confirmed that IL-6 enhances transcription of
      C13orf25 through this distinct region. Finally, we showed that persistent
      activation of STAT3 leads to repressed protein expression of BMPR2. Taken
      together, we describe here a novel STAT3-miR-17/92-BMPR2 pathway, thus providing
      a mechanistic explanation for the loss of BMPR2 in the development of pulmonary
      hypertension.

PMID- 19390057
TI  - Phosphodiesterase 2 mediates redox-sensitive endothelial cell proliferation and
      angiogenesis by thrombin via Rac1 and NADPH oxidase 2.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) control the levels of the second
      messengers cAMP and cGMP in many cell types including endothelial cells. Although
      PDE2 has the unique property to be activated by cGMP but to hydrolyze cAMP, its
      role in endothelial function is only poorly understood. Reactive oxygen species
      (ROS) have been recognized as signaling molecules controlling many endothelial
      functions. We thus investigated whether PDE2 would link to ROS generation and
      proliferative responses in human umbilical vein endothelial cells in response to
      thrombin. Thrombin stimulated the GTPase Rac1, known to activate NADPH oxidases,
      and enhanced ROS formation, whereas PDE2 inhibition or depletion by short hairpin
      (sh)RNA prevented these responses. Similar observations were made with 8-Br-cGMP
      or atrial natriuretic peptide. In agreement, thrombin elevated cGMP but decreased
      cAMP levels, whereas db-cAMP or forskolin diminished Rac1 activity and ROS
      production. Subsequently, PDE2 overexpression activated Rac1, increased ROS
      generation, and enhanced proliferation and in vitro capillary formation. These
      responses were not observed in the presence of inactive Rac1 or shRNA against the
      NADPH oxidase subunit NOX2. Inhibition or depletion of PDE2 also prevented
      thrombin-induced proliferation and capillary formation. Importantly,
      downregulation of PDE2 by lentiviral shRNA or PDE2 inhibition prevented vessel
      sprouting from mouse aortic explants and in vivo angiogenesis in a mouse model,
      respectively. In summary, PDE2 promotes activation of NADPH oxidase-dependent ROS
      production and subsequent endothelial proliferation and angiogenesis. Targeting
      PDE2 may provide a new therapeutic approach in diseases associated with
      endothelial dysfunction, oxidative stress, vascular proliferation, and
      angiogenesis.

PMID- 19390058
TI  - Multipotent progenitor cells are present in human peripheral blood.
AB  - To determine whether the peripheral blood in humans contains a population of
      multipotent progenitor cells (MPCs), products of leukapheresis were obtained from
      healthy donor volunteers following the administration of granulocyte colony
      stimulating factor. Small clusters of adherent proliferating cells were
      collected, and these cells continued to divide up to 40 population doublings
      without reaching replicative senescence and growth arrest. MPCs were positive for
      the transcription factors Nanog, Oct3/4, Sox2, c-Myc, and Klf4 and expressed
      several antigens characteristic of mesenchymal stem cells. However, they were
      negative for markers of hematopoietic stem/progenitor cells and bone marrow cell
      lineages. MPCs had a cloning efficiency of approximately 3%, and following their
      expansion, retained a highly immature phenotype. Under permissive culture
      conditions, MPCs differentiated into neurons, glial cells, hepatocytes,
      cardiomyocytes, endothelial cells, and osteoblasts. Moreover, the gene expression
      profile of MPCs partially overlapped with that of neural and embryonic stem
      cells, further demonstrating their primitive, uncommitted phenotype. Following
      subcutaneous transplantation in nonimmunosuppressed mice, MPCs migrated to
      distant organs and integrated structurally and functionally within the new
      tissue, acquiring the identity of resident parenchymal cells. In conclusion,
      undifferentiated cells with properties of embryonic stem cells can be isolated
      and expanded from human peripheral blood after granulocyte colony-stimulating
      factor administration. This cell pool may constitute a unique source of
      autologous cells with critical clinical import.

PMID- 19390059
TI  - On the trail of microparticles.

PMID- 19390049
TI  - The genome sequence of taurine cattle: a window to ruminant biology and
      evolution.
AB  - To understand the biology and evolution of ruminants, the cattle genome was
      sequenced to about sevenfold coverage. The cattle genome contains a minimum of
      22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian
      species of which 1217 are absent or undetected in noneutherian (marsupial or
      monotreme) genomes. Cattle-specific evolutionary breakpoint regions in
      chromosomes have a higher density of segmental duplications, enrichment of
      repetitive elements, and species-specific variations in genes associated with
      lactation and immune responsiveness. Genes involved in metabolism are generally
      highly conserved, although five metabolic genes are deleted or extensively
      diverged from their human orthologs. The cattle genome sequence thus provides a
      resource for understanding mammalian evolution and accelerating livestock genetic
      improvement for milk and meat production.

PMID- 19390060
TI  - A dual role of CD4+ T cells in adipose tissue?

PMID- 19390062
TI  - Signaling pathways controlling second heart field development.
AB  - Insight into the mechanisms underlying congenital heart defects and the use of
      stem cells for cardiac repair are major research goals in cardiovascular biology.
      In the early embryo, progenitor cells in pharyngeal mesoderm contribute to the
      rapid growth of the heart tube during looping morphogenesis. These progenitor
      cells constitute the second heart field (SHF) and were first identified in 2001.
      Direct or indirect perturbation of SHF addition to the heart results in
      congenital heart defects, including arterial pole alignment defects. Over the
      last 3 years, a number of studies have identified key intercellular signaling
      pathways that control the proliferation and deployment of SHF progenitor cells.
      Here, we review data concerning Wnt, fibroblast growth factor, bone morphogenetic
      protein, Hedgehog, and retinoic acid signaling that have begun to identify the
      ligand sources and responding cell types controlling SHF development. These
      studies have revealed the importance of signals from pharyngeal mesoderm itself,
      as well as critical inputs from adjacent pharyngeal epithelia and neural crest
      cells. Proliferation is emerging as a central checkpoint in the regulation of SHF
      development. Together, these studies contribute to defining the niche of cardiac
      progenitor cells in the early embryo, and we discuss the implications of these
      findings for the regulation of resident stem cell populations in the fetal and
      postnatal heart. Characterization of signals that maintain, expand, and regulate
      the differentiation of cardiac progenitor cells is essential for understanding
      both the etiology of congenital heart defects and the biomedical application of
      stem cell populations for cardiac repair.

PMID- 19390061
TI  - Extracellular matrix differentiating good flow versus bad flow.

PMID- 19390063
TI  - A prospective study using the ABCD2 score in screening for minor stroke or
      transient ischaemic attack in referrals to a fast track clinic.

PMID- 19390064
TI  - Does diet influence the retinal microvasculature in children?

PMID- 19390065
TI  - Dispatcher recognition of stroke using the National Academy Medical Priority
      Dispatch System.
AB  - BACKGROUND AND PURPOSE: Emergency medical dispatchers play an important role in
      optimizing stroke care if they are able to accurately identify calls regarding
      acute cerebrovascular disease. This study was undertaken to assess the diagnostic
      accuracy of the current national protocol guiding dispatcher questioning of 911
      callers to identify stroke (QA Guide version 11.1 of the National Academy Medical
      Priority Dispatch System). METHODS: We identified all Los Angeles Fire Department
      paramedic transports of patients to University of California Los Angeles Medical
      Center during the 12-month period from January to December 2005 in a
      prospectively maintained database. Dispatcher-assigned Medical Priority Dispatch
      System codes for each of these patient transports were abstracted from the
      paramedic run sheets and compared to final hospital discharge diagnosis. RESULTS:
      Among 3474 transported patients, 96 (2.8%) had a final diagnosis of stroke or
      transient ischemic attack. Dispatchers assigned a code of potential stroke to
      44.8% of patients with a final discharge diagnosis of stroke or TIA. Dispatcher
      identification of stroke showed a sensitivity of 0.41, specificity of 0.96,
      positive predictive value of 0.45, and negative predictive value of 0.95.
      CONCLUSIONS: Dispatcher recognition of stroke calls using the widely employed
      Medical Priority Dispatch System algorithm is suboptimal, with failure to
      identify more than half of stroke patients as likely stroke. Revisions to the
      current national dispatcher structured interview and symptom identification
      algorithm for stroke may facilitate more accurate recognition of stroke by
      emergency medical dispatchers.

PMID- 19390066
TI  - Mechanical approaches combined with intra-arterial pharmacological therapy are
      associated with higher recanalization rates than either intervention alone in
      revascularization of acute carotid terminus occlusion.
AB  - BACKGROUND AND PURPOSE: Acute stroke attributable to internal carotid artery
      terminus occlusion carries a poor prognosis. Vessel recanalization is crucial to
      improve clinical outcome. Historically, pharmacological thrombolysis alone has
      low recanalization rates. We sought to determine whether adjunctive mechanical
      approaches achieve better vessel recanalization and functional outcome. METHODS:
      We retrospectively reviewed 75 consecutive endovascular cases of acute internal
      carotid artery terminus occlusions treated at our center between 1998 and 2008.
      Mechanical approaches (MERCI retrieval/angioplasty/stent) with and without
      adjunctive intra-arterial pharmacological therapy (urokinase or tissue
      plasminogen activator) was compared to intra-arterial lytics alone. Univariate
      and multivariate analyses were performed to determine predictors of
      recanalization (thrombolysis in myocardial infarction grades 2 to 3) and
      favorable functional outcome (modified Rankin score <or=2) at 3 months. RESULTS:
      Lowest recanalization rates were observed with intra-arterial lytics alone (3/17,
      17.6%). MERCI embolectomy combined with intra-arterial lytics was associated with
      the highest recanalization rates (18/21, 85.7%; P<0.0001). MERCI embolectomy
      alone achieved 46.2% recanalization rates (6/13; P=0.23). Angioplasty or stenting
      and intra-arterial lytics achieved 25% (2/8; P=0.65) and 40% (4/10; P=0.085)
      recanalization, respectively. In multivariate analysis, combination of MERCI
      embolectomy with intra-arterial lytics (OR, 16.2; CI, 4.6-77.6), or any
      mechanical technique with intra-arterial lytics (OR, 6.7; CI, 2.5-19.5)
      independently predicted thrombolysis in myocardial infarction 2 to 3
      recanalization. Clinically significant parenchymal hemorrhage rates were 7.5%
      with combination (3/38) and 12.5% with pharmacological therapies (2/16; P=0.46).
      Using stepwise logistic regression, age (OR, 0.95; CI, 0.90-0.995), baseline
      NIHSS (OR, 0.82; CI, 0.70-0.96), and thrombolysis in myocardial infarction 2 to 3
      recanalization (OR, 4.0; CI, 1.1-14.4) were associated with favorable functional
      outcome. CONCLUSIONS: Combined mechanical and intra-arterial pharmacological
      therapy is associated with higher recanalization rates than either intervention
      alone in acute internal carotid artery terminus occlusion revascularization.

PMID- 19390067
TI  - Intravenous thrombolysis for acute ischemic stroke: time is prime.

PMID- 19390068
TI  - European Cooperative Acute Stroke Study III: support for and questions about a
      truly emerging therapy.

PMID- 19390069
TI  - A randomized controlled trial of mental imagery augment generalization of
      learning in acute poststroke patients.
AB  - BACKGROUND AND PURPOSE: Our previous studies demonstrated that mental imagery
      intervention enhanced poststroke patients relearning daily task performance. This
      study aimed to test the efficacy of mental imagery for promoting generalization
      of the task skills learned in a training environment to trained and untrained
      tasks carried out in a novel environment. METHODS: Thirty-five acute poststroke
      patients were randomly assigned to the mental imagery (MI; n=18) or conventional
      functional rehabilitation (FR; n=17) group. The MI intervention was 3-week
      standardized practices and daily tasks using the chunking-regulation-rehearsal
      strategies. Outcome measurements were the performances on trained and untrained
      tasks in the training and novel environments. RESULTS: The MI patients showed
      significantly better performances on 4 of 5 trained tasks (P=0.001 to 0.026)
      versus only 1 task in the FR patients (P=0.021). The MI patients also
      outperformed their FR counterpart on the 3 (of 5) (P=0.025 to 0.049) trained and
      2 (of 3) untrained tasks (P=0.042 to 0.045) carried out in the novel environment.
      CONCLUSIONS: The mental imagery intervention was useful for improving patients'
      ability on performing the tasks which they did not previously trained on and in
      places different from the training environments. These involved generalization of
      the skills learned at the task performance level. Our findings are limited to
      poststoke patients who share similar characteristics with those in this study.

PMID- 19390071
TI  - After European Cooperative Acute Stroke Study 3: mission accomplished?

PMID- 19390070
TI  - Severe cerebral white matter hyperintensities predict severe cognitive decline in
      patients with cerebrovascular disease history.
AB  - BACKGROUND AND PURPOSE: Cerebral white matter hyperintensities (WMHs) are
      believed to be the consequence of small vessel disease, and it is uncertain
      whether their extent predicts the risk of dementia in patients with vascular
      disease history. Method- Brain MRI was performed in 226 participants of the
      PROGRESS study. WMH severity was assessed using a visual rating scale. During
      follow-up, patients were classified for incident severe cognitive deterioration
      (including dementia) using standard criteria. RESULTS: Over 4-year follow-up, the
      incidence of severe cognitive deterioration ranged from 1.1 to 9.1 per 100 person
      years in patients with respectively no or severe WMHs at baseline. In
      multivariable analysis, incident severe cognitive deterioration was associated
      with baseline severe WMHs (odds ratio=7.7, P<0.005). CONCLUSIONS: Higher WMH load
      is a strong predictor of dementia and cognitive decline in patients with
      cerebrovascular disease history.

PMID- 19390072
TI  - Ischemic stroke in South Asians: a review of the epidemiology, pathophysiology,
      and ethnicity-related clinical features.
AB  - BACKGROUND AND PURPOSE: Within the United Kingdom, mortality from stroke is
      higher among South Asians compared to European whites. The reasons for this
      excess cerebrovascular risk in South Asians remain unclear. The aim of this
      review is to present a comprehensive and systematic overview of the available
      literature relating to ischemic stroke among South Asian populations identifying
      distinct features of stroke epidemiology in this group. SUMMARY OF REVIEW: A high
      frequency of lacunar strokes is a familiar pattern among South Asians, which
      suggests a greater prevalence of small-vessel disease in South Asians. This may
      be a consequence of abnormal metabolic and glycemic processes. In addition,
      stroke mortality among South Asians appears to be explained by glycemic status,
      which is an independent predictor of long-term stroke mortality. Within India,
      there is a perceptible rural-urban gradient in stroke prevalence, underlying the
      dangers of the rapid transition in socioeconomic circumstances seen across the
      Indian subcontinent. CONCLUSIONS: This review emphasizes the importance of
      further research into ischemic stroke for South Asians given their higher
      cardiovascular disease burden and necessity for targeted healthcare approaches.

PMID- 19390073
TI  - The genetics of cervical artery dissection: a systematic review.
AB  - BACKGROUND AND PURPOSE: The pathophysiology of cervical artery dissections (CAD),
      a major cause of ischemic stroke in young adults, is poorly understood. Several
      arguments suggest a genetic predisposition. METHODS: We systematically reviewed
      all published data on genetic risk factors for CAD and performed a meta-analysis
      of association studies with the MTHFR C677T polymorphism. RESULTS: Rarely, CAD is
      associated with a known monogenic connective tissue disease, mainly vascular
      Ehlers-Danlos syndrome. However, in the large majority of CAD cases, there is no
      evidence for a known monogenic disease. Several arguments, including the
      association of CAD with dermal connective tissue abnormalities that are
      inherited, suggest that genetic factors also play a role in "sporadic" CAD as
      part of a multifactorial predisposition. We identified 15 genetic association
      studies: 10 were negative and 5 reported associations of 3 genetic variants in 3
      different candidate genes. Two studies reported associations with polymorphisms
      in ICAM-1 and COL3A1, but neither has been replicated. Three studies reported an
      association with the MTHFR 677TT genotype, but 3 other studies did not replicate
      this. A meta-analysis of these data identified an overall significant association
      of the MTHFR 677TT genotype with CAD (OR, 1.67; 95% CI, 1.21 to 2.31). We also
      identified 9 studies screening candidate genes for mutations and 4 linkage
      studies, yielding mostly negative results. CONCLUSIONS: Although several
      interesting hypotheses were generated, the majority of genetic studies in CAD
      have been negative until now, but they were markedly underpowered. Progress in
      unraveling the genetics of CAD will require the collection of DNA samples from
      large multicenter series.

PMID- 19390074
TI  - What are the social consequences of stroke for working-aged adults? A systematic
      review.
AB  - BACKGROUND AND PURPOSE: Approximately one fourth of strokes occur in people aged
      <65 years. UK current policy calls for services that meet the specific needs of
      working-aged adults with stroke. We aimed to identify the social consequences of
      stroke in working-aged adults, which might subsequently inform the development
      and evaluation of services for this group. METHODS: We reviewed quantitative and
      qualitative studies identifying social consequences for working-aged adults with
      stroke using multiple search strategies (electronic databases, bibliographic
      references, hand searches). Social consequences were defined as those pertaining
      to the World Health Organization International Classification of Functioning,
      Disability and Health domain "participation." Two authors reviewed articles using
      a standardized matrix for data extraction. RESULTS: Seventy-eight studies were
      included: 66 were quantitative observational studies, 2 were quantitative
      interventional studies, 9 were qualitative studies, and one used mixed methods.
      Seventy studies reported data on return to work after stroke with proportions
      ranging from 0% to 100%. Other categories of social consequences included
      negative impact on family relationships (5% to 54%), deterioration in sexual life
      (5% to 76%), economic difficulties (24% to 33%), and deterioration in leisure
      activities (15% to 79%). CONCLUSIONS: Methodological variations account for the
      wide range of rates of return to work after stroke. There is limited evidence of
      the negative impact of stroke on other aspects of social participation. Robust
      estimates of the prevalence of such outcomes are required to inform the
      development of appropriate interventions. We propose strategies by which
      methodology and reporting in this field might be improved.

PMID- 19390075
TI  - The presentation and clinical course of intracranial developmental venous
      anomalies in adults: a systematic review and prospective, population-based study.
AB  - BACKGROUND AND PURPOSE: Reported risks of hemorrhage from intracranial
      developmental venous anomalies (DVAs) vary, so we investigated this in a
      systematic review and population-based study. METHODS: We systematically reviewed
      the literature (Ovid Medline and Embase to November 7, 2007) and selected studies
      of >or=20 participants with >or=1 DVA(s) that described their clinical
      presentation and/or their clinical course over a specified follow-up period. We
      also identified every adult first diagnosed with a DVA in Scotland from 1999 to
      2003 and followed them in a prospective, population-based study. RESULTS: Of 2068
      articles detected by the literature search, 15 met our inclusion criteria and
      described clinical presentation, 8 of which also described the clinical course of
      DVAs. In the 15 studies of 714 people first presenting with a DVA, 61% were
      incidental findings, the mode of presentation was unclear in 23%, 6% presented
      with nonhemorrhagic focal neurological deficit, 6% had caused symptomatic
      hemorrhage, 4% were associated with epileptic seizure, and <1% were associated
      with infarction. In studies of the clinical course of 422 people with a DVA, the
      hemorrhage rate after first presentation ranged from 0% to 1.28% per year. In the
      population-based study of 93 adults with DVAs, 98% were incidental, 1% presented
      with symptomatic hemorrhage, and 1% presented with an infarct, but there were no
      symptomatic hemorrhages or infarcts in 492 person-years of follow-up (0% per
      person-year; 95% CI, 0% to 0.7%). CONCLUSIONS: Intracranial DVAs have a benign
      presentation and clinical course.

PMID- 19390076
TI  - Hemodynamic factors and perfusion abnormalities in early neurological
      deterioration.
AB  - BACKGROUND AND PURPOSE: Early neurological deterioration (END) is a relatively
      common unfavorable course after anterior circulation ischemic stroke that can
      lead to worse clinical outcome. None of the END predictors identified so far is
      sufficiently reliable to be used in clinical practice and the mechanisms
      underlying END are not fully understood. We review the evidence from the
      literature for a role of hemodynamic and perfusion abnormalities, more
      specifically infarction of the oligemia, in END: SUMMARY OF REVIEW: After an
      overview of the neuroimaging, including perfusion imaging, predictors of END, we
      review the putative mechanisms of END with a special focus on hemodynamic
      factors. The evidence relating perfusion abnormalities to END is addressed and
      potential hemodynamic mechanisms are suggested. CONCLUSIONS: Hemodynamic factors
      and perfusion abnormalities are likely to play a critical role in END: Infarction
      of the oligemic tissue surrounding the penumbra could be the putative culprit
      leading to END as a result of perfusion, but also physiological and biochemical
      abnormalities. Further studies addressing the role of the oligemia in END and
      developing measures to protect its progression to infarction are now needed.

PMID- 19390077
TI  - Management of blood pressure for acute and recurrent stroke.

PMID- 19390078
TI  - Hyperglycemia and clinical outcome in aneurysmal subarachnoid hemorrhage: a meta
      analysis.
AB  - BACKGROUND AND PURPOSE: Hyperglycemia may worsen outcome after aneurysmal
      subarachnoid hemorrhage. We performed a systematic review to investigate the
      relation between admission hyperglycemia and outcome after aneurysmal
      subarachnoid hemorrhage. METHODS: We included cohort studies or clinical trials
      of patients with aneurysmal subarachnoid hemorrhage admitted within 72 hours that
      documented admission glucose levels or the rate of hyperglycemia. Outcome had to
      be assessed prospectively after 3 or more months. The overall mean glucose level
      was calculated by weighting for the number of patients included in each study. To
      calculate the effect size, we pooled the ORs and 95% 95% CIs of poor clinical
      outcome in patients with or without hyperglycemia. RESULTS: We searched MEDLINE,
      EMBASE, Science Citation Index, and the bibliographies of relevant studies. We
      included 17 studies totaling 4095 patients. The mean admission glucose level was
      9.3 mmol/L (range, 7.4 to 10.9 mmol/L; 14 studies, 3373 patients) and the median
      proportion of patients with hyperglycemia was 69% (range, 29 to 100; 16 studies,
      3995 patients; cutoff levels of hyperglycemia, 5.7 to 12.0 mmol/L). The pooled OR
      (8 studies, 2164 patients) for poor outcome associated with hyperglycemia was 3.1
      (95% CI, 2.3 to 4.3). Cutoff points for defining hyperglycemia varied across
      studies (6.4 to 11.1 mmol/L), but this had no clear effect on the observed OR for
      poor outcome. CONCLUSIONS: After aneurysmal subarachnoid hemorrhage, admission
      glucose levels are often high and hyperglycemia is associated with an increased
      risk of poor clinical outcome. A randomized clinical trial is warranted to study
      the potential benefit of glycemic control after aneurysmal subarachnoid
      hemorrhage.

PMID- 19390079
TI  - Effect of antiplatelet therapy for endovascular coiling in aneurysmal
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Antiplatelets are frequently used during or after
      endovascular coiling of aneurysm in patients with subarachnoid hemorrhage (SAH).
      This strategy is based on uncontrolled case series including also patients with
      unruptured aneurysms or other lesions. We collected data on effectiveness of
      antiplatelets in patients with SAH. METHODS: All 43 participating centers in the
      International Subarachnoid Aneurysm Trial (ISAT) were sent a questionnaire
      whether they never, sometimes, or always prescribed antiplatelets during or after
      coiling. Based on individual patient data, the relative risks (RRs) of coiling
      versus clipping were calculated separately for patients treated in hospitals with
      standard prescription during or after coiling versus patients treated in
      hospitals with no standard prescription of antiplatelets. We calculated ratios of
      RRs for standard versus not standard prescription of antiplatelets during coiling
      and for standard versus not standard prescription after coiling. RESULTS:
      Nineteen centers responded, representing 1422 (66%) of the 2143 ISAT patients.
      Antiplatelets were standard prescribed during coiling in 2 responding centers (8%
      of coiled patients) and after coiling in 6 centers (24%). For poor outcome at 2
      months of coiling versus clipping the RR was 0.82 (95% CI: 0.45 to 1.49) in
      hospitals with a policy of antiplatelet prescription during coiling versus 0.66
      (95% CI: 0.55 to 0.78) in those without such policy (ratio of RR's 1.24, P=0.56).
      The ratio of RRs for 1-year outcome was 1.01 (P=0.89) for antiplatelet use during
      coiling and 1.00 (P=0.77) for use after coiling. CONCLUSIONS: The results of this
      study do not support the assumption that antiplatelets during or after
      endovascular coiling improve outcome in patients with SAH.

PMID- 19390080
TI  - Potential animal models of lacunar stroke: a systematic review.
AB  - BACKGROUND AND PURPOSE: Lacunar ischemic stroke accounts for 25% of all ischemic
      strokes, but the exact etiology is unknown. Numerous pathophysiologies have been
      proposed, including atheroma and endothelial dysfunction. Models of any of these
      pathological features would aid understanding of the etiology and help develop
      treatments for lacunar stroke. We therefore aimed to assess the relevance of all
      available potential animal models of lacunar stroke. METHODS: We systematically
      reviewed the published literature for animal models that could represent lacunar
      stroke using validated search strategies. We included studies that could
      represent an aspect of lacunar stroke as well as those aiming to model conditions
      with potentially similar pathology and extracted data on species, induction
      method, and resulting brain and vessel lesions. RESULTS: From 5670 papers, 41
      studies (46 papers) met inclusion criteria representing over 10 different classes
      of stroke induction. Important data like infarct size and animal numbers were
      often missing. Many models' infarcts were too large or affected the cortex.
      Emboli mostly caused cortical but not small subcortical lesions. Most models
      focused on creating ischemic lesions in brain tissue. Only one (spontaneous
      lesions in spontaneously hypertensive stroke-prone rats) also mimicked small
      vessel pathology. Here, the precursor to small vessel and brain damage was blood
      brain barrier failure. CONCLUSIONS: Some animal models produce small subcortical
      infarcts, but few mimic the human small vessel pathology. Models of small vessel
      disease could help improve understanding of human lacunar disease, particularly
      to clarify factors associated with the small vessel morphological changes
      preceding brain damage. Much lacunar stroke may arise after blood-brain barrier
      disruption.

PMID- 19390081
TI  - Importance of blood pressure control in hypertensive patients with coronary heart
      disease in clinical practice to reduce the risk of stroke.

PMID- 19390082
TI  - Active destruction of defective ribosomes by a ubiquitin ligase involved in DNA
      repair.
AB  - Progression of DNA replication forks through damaged DNA requires a ubiquitin
      ligase comprised of the cullin Rtt101, the RING finger protein Hrt1, and the
      adaptor protein Mms1. Rtt101 and Mms1 were implicated recently by Fujii and
      colleagues (pp. 963-974) in the degradation of catalytically inactive mutant 25S
      ribosomal RNAS (rRNAs) in mature 60S ribosomal subunits, a process that requires
      ubiquitin and is accompanied by ubiquitination of 60S components. It now seems
      likely that the same ubiquitin ligase is enlisted to deal with defective rRNA and
      damaged DNA.

PMID- 19390083
TI  - Single cells (put a ring on it).
AB  - Proper spatial and temporal regulation of the small GTPase RhoA at the equatorial
      cortex represents a critical step in the specification of the division plane in
      eukaryotes. Despite increased understanding of the mechanisms whereby RhoA
      becomes active following chromosome segregation, far less is known about how RhoA
      is spatially regulated so that it concentrates precisely at the division site. In
      the April 1, 2009, issue of Genes & Development, Yoshida and colleagues (pp. 810
      823) uncovered two genetically separable mechanisms whereby Rho1 is recruited to
      the bud neck in the budding yeast Saccharomyces cerevisiae to facilitate
      cytokinesis.

PMID- 19390084
TI  - The origin of embryonic and fetal myoblasts: a role of Pax3 and Pax7.
AB  - Skeletal muscle is a heterogeneous tissue composed of individual muscle fibers,
      diversified in size, shape, and contractile protein content, to fulfill the
      different functional needs of the vertebrate body. This heterogeneity derives
      from and depends at least in part on distinct classes of myogenic progenitors;
      i.e., embryonic and fetal myoblasts and satellite cells whose origin and lineage
      relationship have been elusive so far. In this issue of Genes & Development,
      Hutcheson and colleagues (pp. 997-1013) provide a first answer to this question.

PMID- 19390085
TI  - Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell
      proliferation.
AB  - The molecular mechanisms that regulate the age-induced increase of p16(INK4a)
      expression associated with decreased beta-cell proliferation and regeneration are
      not well understood. We report that in aged islets, derepression of the Ink4a/Arf
      locus is associated with decreased Bmi-1 binding, loss of H2A ubiquitylation,
      increased MLL1 recruitment, and a concomitant increase in H3K4 trimethylation.
      During beta-cell regeneration these histone modifications are reversed resulting
      in reduced p16(INK4a) expression and increased proliferation. We suggest that PcG
      and TrxG proteins impart a combinatorial code of histone modifications on the
      Ink4a/Arf locus to control beta-cell proliferation during aging and regeneration.

PMID- 19390086
TI  - Mechanisms that regulate localization of a DNA double-strand break to the nuclear
      periphery.
AB  - DNA double-strand breaks (DSBs) are among the most deleterious forms of DNA
      lesions in cells. Here we induced site-specific DSBs in yeast cells and monitored
      chromatin dynamics surrounding the DSB using Chromosome Conformation Capture
      (3C). We find that formation of a DSB within G1 cells is not sufficient to alter
      chromosome dynamics. However, DSBs formed within an asynchronous cell population
      result in large decreases in both intra- and interchromosomal interactions. Using
      live cell microscopy, we find that changes in chromosome dynamics correlate with
      relocalization of the DSB to the nuclear periphery. Sequestration to the
      periphery requires the nuclear envelope protein, Mps3p, and Mps3p-dependent
      tethering delays recombinational repair of a DSB and enhances gross chromosomal
      rearrangements. Furthermore, we show that components of the telomerase machinery
      are recruited to a DSB and that telomerase recruitment is required for its
      peripheral localization. Based on these findings, we propose that sequestration
      of unrepaired or slowly repaired DSBs to the nuclear periphery reflects a
      competition between alternative repair pathways.

PMID- 19390087
TI  - Yeast telomerase and the SUN domain protein Mps3 anchor telomeres and repress
      subtelomeric recombination.
AB  - Telomeres form the ends of linear chromosomes and protect these ends from being
      recognized as DNA double-strand breaks. Telomeric sequences are maintained in
      most cells by telomerase, a reverse transcriptase that adds TG-rich repeats to
      chromosome ends. In budding yeast, telomeres are organized in clusters at the
      nuclear periphery by interactions that depend on components of silent chromatin
      and the telomerase-binding factor yeast Ku (yKu). In this study, we examined
      whether the subnuclear localization of telomeres affects end maintenance. A
      telomere anchoring pathway involving the catalytic yeast telomerase subunits
      Est2, Est1, and Tlc1 is shown to be necessary for the perinuclear anchoring
      activity of Yku80 during S phase. Additionally, we identify the conserved Sad1
      UNC-84 (SUN) domain protein Mps3 as the principal membrane anchor for this
      pathway. Impaired interference with Mps3 anchoring through overexpression of the
      Mps3 N terminus in a tel1 deletion background led to a senescence phenotype and
      to deleterious levels of subtelomeric Y' recombination. This suggests that
      telomere binding to the nuclear envelope helps protect telomeric repeats from
      recombination. Our results provide an example of a specialized structure that
      requires proper spatiotemporal localization to fulfill its biological role, and
      identifies a novel pathway of telomere protection.

PMID- 19390088
TI  - Compromised stability of DNA methylation and transposon immobilization in mosaic
      Arabidopsis epigenomes.
AB  - Transgenerational epigenetic inheritance has been defined by the study of
      relatively few loci. We examined a population of recombinant inbred lines with
      epigenetically mosaic chromosomes consisting of wild-type and CG methylation
      depleted segments (epiRILs). Surprisingly, transposons that were immobile in the
      parental lines displayed stochastic movement in 28% of the epiRILs. Although
      analysis after eight generations of inbreeding, supported by genome-wide DNA
      methylation profiling, identified recombined parental chromosomal segments, these
      were interspersed with unexpectedly high frequencies of nonparental methylation
      polymorphism. Hence, epigenetic inheritance in hybrids derived from parents with
      divergent epigenomes permits long-lasting epi-allelic interactions that violate
      Mendelian expectations. Such persistently "unstable" epigenetic states complicate
      linkage-based epigenomic mapping. Thus, future epigenomic analyses should
      consider possible genetic instabilities and alternative mapping strategies.

PMID- 19390089
TI  - A role for ubiquitin in the clearance of nonfunctional rRNAs.
AB  - Quality control mechanisms operate in various steps of ribosomal biogenesis to
      ensure the production of functional ribosome particles. It was reported
      previously that mature ribosome particles containing nonfunctional mutant rRNAs
      are also recognized and selectively removed by a cellular quality control system
      (nonfunctional rRNA decay [NRD]). Here, we show that the NRD of 25S rRNA requires
      a ubiquitin E3 ligase component Rtt101p and its associated protein Mms1p,
      identified previously as factors involved in DNA repair. We revealed that a group
      of proteins associated with nonfunctional ribosome particles are ubiquitinated in
      a Rtt101-Mms1-dependent manner. 25S NRD was disrupted when ubiquitination was
      inhibited by the overexpression of modified ubiquitin molecules, demonstrating a
      direct role for ubiquitin in this pathway. These results uncovered an unexpected
      connection between DNA repair and the quality control of rRNAs. Our findings
      support a model in which responses to DNA and rRNA damages are triggered by a
      common ubiquitin ligase complex during genotoxic stress harmful to both
      molecules.

PMID- 19390090
TI  - Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and
      regeneration in diabetes mellitus.
AB  - Proliferation of pancreatic islet beta cells is an important mechanism for self
      renewal and for adaptive islet expansion. Increased expression of the Ink4a/Arf
      locus, which encodes the cyclin-dependent kinase inhibitor p16(INK4a) and tumor
      suppressor p19(Arf), limits beta-cell regeneration in aging mice, but the basis
      of beta-cell Ink4a/Arf regulation is poorly understood. Here we show that
      Enhancer of zeste homolog 2 (Ezh2), a histone methyltransferase and component of
      a Polycomb group (PcG) protein complex, represses Ink4a/Arf in islet beta cells.
      Ezh2 levels decline in aging islet beta cells, and this attrition coincides with
      reduced histone H3 trimethylation at Ink4a/Arf, and increased levels of
      p16(INK4a) and p19(Arf). Conditional deletion of beta-cell Ezh2 in juvenile mice
      also reduced H3 trimethylation at the Ink4a/Arf locus, leading to precocious
      increases of p16(INK4a) and p19(Arf). These mutant mice had reduced beta-cell
      proliferation and mass, hypoinsulinemia, and mild diabetes, phenotypes rescued by
      germline deletion of Ink4a/Arf. beta-Cell destruction with streptozotocin in
      controls led to increased Ezh2 expression that accompanied adaptive beta-cell
      proliferation and re-establishment of beta-cell mass; in contrast, mutant mice
      treated similarly failed to regenerate beta cells, resulting in lethal diabetes.
      Our discovery of Ezh2-dependent beta-cell proliferation revealed unique
      epigenetic mechanisms underlying normal beta-cell expansion and beta-cell
      regenerative failure in diabetes pathogenesis.

PMID- 19390091
TI  - Bile acid signaling pathways increase stability of Small Heterodimer Partner
      (SHP) by inhibiting ubiquitin-proteasomal degradation.
AB  - Small Heterodimer Partner (SHP) inhibits activities of numerous transcription
      factors involved in diverse biological pathways. As an important metabolic
      regulator, SHP plays a key role in maintaining cholesterol and bile acid
      homeostasis by inhibiting cholesterol conversion to bile acids. While SHP gene
      induction by increased bile acids is well established, whether SHP activity is
      also modulated remains unknown. Here, we report surprising findings that SHP is a
      rapidly degraded protein via the ubiquitin-proteasomal pathway and that bile
      acids or bile acid-induced intestinal fibroblast growth factor 19 (FGF19)
      increases stability of hepatic SHP by inhibiting proteasomal degradation in an
      extracellular signal-regulated kinase (ERK)-dependent manner. SHP was
      ubiquitinated at Lys122 and Lys123, and mutation of these sites altered its
      stability and repression activity. Tandem mass spectrometry revealed that upon
      bile acid treatment, SHP was phosphorylated at Ser26, within an ERK motif in SHP,
      and mutation of this site dramatically abolished SHP stability. Surprisingly, SHP
      stability was abnormally elevated in ob/ob mice and diet-induced obese mice.
      These results demonstrate an important role for regulation of SHP stability in
      bile acid signaling in normal conditions, and that abnormal stabilization of SHP
      may be associated with metabolic disorders, including obesity and diabetes.

PMID- 19390092
TI  - A feeding tube model for activation of a cell-specific transcription factor
      during sporulation in Bacillus subtilis.
AB  - Spore formation by Bacillus subtilis takes place in a sporangium consisting of
      two chambers, the forespore and the mother cell, which are linked by pathways of
      intercellular communication. One pathway, which couples the activation of the
      forespore transcription factor sigma(G) to the action of sigma(E) in the mother
      cell, has remained mysterious. Traditional models hold that sigma(E) initiates a
      signal transduction pathway that specifically activates sigma(G) in the
      forespore. Recent experiments indicating that the mother cell and forespore are
      joined by a channel have led to the suggestion that a specific regulator of
      sigma(G) is transported from the mother cell into the forespore. As we report
      here, however, the requirement for the channel is not limited to sigma(G).
      Rather, it is also required for the persistent activity of the early-acting
      forespore transcription factor sigma(F) as well as that of a heterologous RNA
      polymerase (that of phage T7). We infer that macromolecular synthesis in the
      forespore becomes dependent on the channel at intermediate stages of development.
      We propose that the channel is a gap junction-like feeding tube through which the
      mother cell nurtures the developing spore by providing small molecules needed for
      biosynthetic activity, including sigma(G)-directed gene activation.

PMID- 19390094
TI  - The relationship between electronic health record use and quality of care over
      time.
AB  - OBJECTIVE Electronic health records (EHRs) have the potential to advance the
      quality of care, but studies have shown mixed results. The authors sought to
      examine the extent of EHR usage and how the quality of care delivered in
      ambulatory care practices varied according to duration of EHR availability.
      METHODS The study linked two data sources: a statewide survey of physicians'
      adoption and use of EHR and claims data reflecting quality of care as indicated
      by physicians' performance on widely used quality measures. Using four years of
      measurement, we combined 18 quality measures into 6 clinical condition
      categories. While the survey of physicians was cross-sectional, respondents
      indicated the year in which they adopted EHR. In an analysis accounting for
      duration of EHR use, we examined the relationship between EHR adoption and
      quality of care. RESULTS The percent of physicians reporting adoption of EHR and
      availability of EHR core functions more than doubled between 2000 and 2005. Among
      EHR users in 2005, the average duration of EHR use was 4.8 years. For all 6
      clinical conditions, there was no difference in performance between EHR users and
      non-users. In addition, for these 6 clinical conditions, there was no consistent
      pattern between length of time using an EHR and physicians performance on quality
      measures in both bivariate and multivariate analyses. CONCLUSIONS In this cross
      sectional study, we found no association between duration of using an EHR and
      performance with respect to quality of care, although power was limited.
      Intensifying the use of key EHR features, such as clinical decision support, may
      be needed to realize quality improvement from EHRs. Future studies should examine
      the relationship between the extent to which physicians use key EHR functions and
      their performance on quality measures over time.

PMID- 19390093
TI  - A randomized trial comparing telemedicine case management with usual care in
      older, ethnically diverse, medically underserved patients with diabetes mellitus:
      5 year results of the IDEATel study.
AB  - CONTEXT Telemedicine is a promising but largely unproven technology for providing
      case management services to patients with chronic conditions and lower access to
      care. OBJECTIVES To examine the effectiveness of a telemedicine intervention to
      achieve clinical management goals in older, ethnically diverse, medically
      underserved patients with diabetes. DESIGN, Setting, and Patients A randomized
      controlled trial was conducted, comparing telemedicine case management to usual
      care, with blinded outcome evaluation, in 1,665 Medicare recipients with
      diabetes, aged >/= 55 years, residing in federally designated medically
      underserved areas of New York State. Interventions Home telemedicine unit with
      nurse case management versus usual care. Main Outcome Measures The primary
      endpoints assessed over 5 years of follow-up were hemoglobin A1c (HgbA1c), low
      density lipoprotein (LDL) cholesterol, and blood pressure levels. RESULTS
      Intention-to-treat mixed models showed that telemedicine achieved net overall
      reductions over five years of follow-up in the primary endpoints (HgbA1c, p =
      0.001; LDL, p < 0.001; systolic and diastolic blood pressure, p = 0.024; p <
      0.001). Estimated differences (95% CI) in year 5 were 0.29 (0.12, 0.46)% for
      HgbA1c, 3.84 (-0.08, 7.77) mg/dL for LDL cholesterol, and 4.32 (1.93, 6.72) mm Hg
      for systolic and 2.64 (1.53, 3.74) mm Hg for diastolic blood pressure. There were
      176 deaths in the intervention group and 169 in the usual care group (hazard
      ratio 1.01 [0.82, 1.24]). CONCLUSIONS Telemedicine case management resulted in
      net improvements in HgbA1c, LDL-cholesterol and blood pressure levels over 5
      years in medically underserved Medicare beneficiaries. Mortality was not
      different between the groups, although power was limited. Trial Registration
      http://clinicaltrials.gov Identifier: NCT00271739.

PMID- 19390095
TI  - Validation study of an automated electronic acute lung injury screening tool.
AB  - OBJECTIVE The authors designed an automated electronic system that incorporates
      data from multiple hospital information systems to screen for acute lung injury
      (ALI) in mechanically ventilated patients. The authors evaluated the accuracy of
      this system in diagnosing ALI in a cohort of patients with major trauma, but
      excluding patients with congestive heart failure (CHF). DESIGN Single-center
      validation study. Arterial blood gas (ABG) data and chest radiograph (CXR)
      reports for a cohort of intensive care unit (ICU) patients with major trauma but
      excluding patients with CHF were screened prospectively for ALI requiring
      intubation by an automated electronic system. The system was compared to a
      reference standard established through consensus of two blinded physician
      reviewers who independently screened the same population for ALI using all
      available ABG data and CXR images. The system's performance was evaluated (1) by
      measuring the sensitivity and overall accuracy, and (2) by measuring concordance
      with respect to the date of ALI identification (vs. reference standard).
      MEASUREMENTS One hundred ninety-nine trauma patients admitted to our level 1
      trauma center with an initial injury severity score (ISS) >/= 16 were evaluated
      for development of ALI in the first five days in an ICU after trauma. Main
      RESULTS The system demonstrated 87% sensitivity (95% confidence interval [CI]
      82.3-91.7) and 89% specificity (95% CI 84.7-93.4). It identified ALI before or
      within the 24-hour period during which ALI was identified by the two reviewers in
      87% of cases. CONCLUSIONS An automated electronic system that screens intubated
      ICU trauma patients, excluding patients with CHF, for ALI based on CXR reports
      and results of ABGs is sufficiently accurate to identify many early cases of ALI.

PMID- 19390096
TI  - Recognizing obesity and comorbidities in sparse data.
AB  - In order to survey, facilitate, and evaluate studies of medical language
      processing on clinical narratives, i2b2 (Informatics for Integrating Biology to
      the Bedside) organized its second challenge and workshop. This challenge focused
      on automatically extracting information on obesity and fifteen of its most common
      comorbidities from patient discharge summaries. For each patient, obesity and any
      of the comorbidities could be Present, Absent, or Questionable (i.e., possible)
      in the patient, or Unmentioned in the discharge summary of the patient. i2b2
      provided data for, and invited the development of, automated systems that can
      classify obesity and its comorbidities into these four classes based on
      individual discharge summaries. This article refers to obesity and comorbidities
      as diseases. It refers to the categories Present, Absent, Questionable, and
      Unmentioned as classes. The task of classifying obesity and its comorbidities is
      called the Obesity Challenge. The data released by i2b2 was annotated for textual
      judgments reflecting the explicitly reported information on diseases, and
      intuitive judgments reflecting medical professionals' reading of the information
      presented in discharge summaries. There were very few examples of some disease
      classes in the data. The Obesity Challenge paid particular attention to the
      performance of systems on these less well-represented classes. A total of 30
      teams participated in the Obesity Challenge. Each team was allowed to submit two
      sets of up to three system runs for evaluation, resulting in a total of 136
      submissions. The submissions represented a combination of rule-based and machine
      learning approaches. Evaluation of system runs shows that the best predictions of
      textual judgments come from systems that filter the potentially noisy portions of
      the narratives, project dictionaries of disease names onto the remaining text,
      apply negation extraction, and process the text through rules. Information on
      disease-related concepts, such as symptoms and medications, and general medical
      knowledge help systems infer intuitive judgments on the diseases.

PMID- 19390097
TI  - Semi-automated construction of decision rules to predict morbidities from
      clinical texts.
AB  - OBJECTIVE In this study the authors describe the system submitted by the team of
      University of Szeged to the second i2b2 Challenge in Natural Language Processing
      for Clinical Data. The challenge focused on the development of automatic systems
      that analyzed clinical discharge summary texts and addressed the following
      question: "Who's obese and what co-morbidities do they (definitely/most likely)
      have?". Target diseases included obesity and its 15 most frequent comorbidities
      exhibited by patients, while the target labels corresponded to expert judgments
      based on textual evidence and intuition (separately). DESIGN The authors applied
      statistical methods to preselect the most common and confident terms and
      evaluated outlier documents by hand to discover infrequent spelling variants. The
      authors expected a system with dictionaries gathered semi-automatically to have a
      good performance with moderate development costs (the authors examined just a
      small proportion of the records manually). MEASUREMENTS Following the standard
      evaluation method of the second Workshop on challenges in Natural Language
      Processing for Clinical Data, the authors used both macro- and microaveraged
      Fbeta=1 measure for evaluation. RESULTS The authors submission achieved a
      microaverage F(beta=1) score of 97.29% for classification based on textual
      evidence (macroaverage F(beta=1) = 76.22%) and 96.42% for intuitive judgments
      (macroaverage F(beta=1) = 67.27%). CONCLUSIONS The results demonstrate the
      feasibility of the authors approach and show that even very simple systems with a
      shallow linguistic analysis can achieve remarkable accuracy scores for
      classifying clinical records on a limited set of concepts.

PMID- 19390098
TI  - A text mining approach to the prediction of disease status from clinical
      discharge summaries.
AB  - OBJECTIVE The authors present a system developed for the Challenge in Natural
      Language Processing for Clinical Data-the i2b2 obesity challenge, whose aim was
      to automatically identify the status of obesity and 15 related co-morbidities in
      patients using their clinical discharge summaries. The challenge consisted of two
      tasks, textual and intuitive. The textual task was to identify explicit
      references to the diseases, whereas the intuitive task focused on the prediction
      of the disease status when the evidence was not explicitly asserted. DESIGN The
      authors assembled a set of resources to lexically and semantically profile the
      diseases and their associated symptoms, treatments, etc. These features were
      explored in a hybrid text mining approach, which combined dictionary look-up,
      rule-based, and machine-learning methods. MEASUREMENTS The methods were applied
      on a set of 507 previously unseen discharge summaries, and the predictions were
      evaluated against a manually prepared gold standard. The overall ranking of the
      participating teams was primarily based on the macro-averaged F-measure. RESULTS
      The implemented method achieved the macro-averaged F-measure of 81% for the
      textual task (which was the highest achieved in the challenge) and 63% for the
      intuitive task (ranked 7(th) out of 28 teams-the highest was 66%). The micro
      averaged F-measure showed an average accuracy of 97% for textual and 96% for
      intuitive annotations. CONCLUSIONS The performance achieved was in line with the
      agreement between human annotators, indicating the potential of text mining for
      accurate and efficient prediction of disease statuses from clinical discharge
      summaries.

PMID- 19390099
TI  - A system for classifying disease comorbidity status from medical discharge
      summaries using automated hotspot and negated concept detection.
AB  - OBJECTIVE Free-text clinical reports serve as an important part of patient care
      management and clinical documentation of patient disease and treatment status.
      Free-text notes are commonplace in medical practice, but remain an under-used
      source of information for clinical and epidemiological research, as well as
      personalized medicine. The authors explore the challenges associated with
      automatically extracting information from clinical reports using their submission
      to the Integrating Informatics with Biology and the Bedside (i2b2) 2008 Natural
      Language Processing Obesity Challenge Task. DESIGN A text mining system for
      classifying patient comorbidity status, based on the information contained in
      clinical reports. The approach of the authors incorporates a variety of automated
      techniques, including hot-spot filtering, negated concept identification, zero
      vector filtering, weighting by inverse class-frequency, and error-correcting of
      output codes with linear support vector machines. MEASUREMENTS Performance was
      evaluated in terms of the macroaveraged F1 measure. RESULTS The automated system
      performed well against manual expert rule-based systems, finishing fifth in the
      Challenge's intuitive task, and 13(th) in the textual task. CONCLUSIONS The
      system demonstrates that effective comorbidity status classification by an
      automated system is possible.

PMID- 19390100
TI  - Natural language processing framework to assess clinical conditions.
AB  - OBJECTIVE The authors developed a natural language processing (NLP) framework
      that could be used to extract clinical findings and diagnoses from dictated
      physician documentation. DESIGN De-identified documentation was made available by
      i2b2 Bio-informatics research group as a part of their NLP challenge focusing on
      obesity and its co-morbidities. The authors describe their approach, which used a
      combination of concept detection, context validation, and the application of a
      variety of rules to conclude patient diagnoses. RESULTS The framework was
      successful at correctly identifying diagnoses as judged by NLP challenge
      organizers when compared with a gold standard of physician annotations. The
      authors overall kappa values for agreement with the gold standard were 0.92 for
      explicit textual results and 0.91 for intuited results. The NLP framework
      compared favorably with those of the other entrants, placing third in textual
      results and fourth in intuited results in the i2b2 competition. CONCLUSIONS The
      framework and approach used to detect clinical conditions was reasonably
      successful at extracting 16 diagnoses related to obesity. The system and
      methodology merits further development, targeting clinically useful applications.

PMID- 19390101
TI  - Semantic classification of diseases in discharge summaries using a context-aware
      rule-based classifier.
AB  - OBJECTIVE Automated and disease-specific classification of textual clinical
      discharge summaries is of great importance in human life science, as it helps
      physicians to make medical studies by providing statistically relevant data for
      analysis. This can be further facilitated if, at the labeling of discharge
      summaries, semantic labels are also extracted from text, such as whether a given
      disease is present, absent, questionable in a patient, or is unmentioned in the
      document. The authors present a classification technique that successfully solves
      the semantic classification task. DESIGN The authors introduce a context-aware
      rule-based semantic classification technique for use on clinical discharge
      summaries. The classification is performed in subsequent steps. First, some
      misleading parts are removed from the text; then the text is partitioned into
      positive, negative, and uncertain context segments, then a sequence of binary
      classifiers is applied to assign the appropriate semantic labels. Measurement For
      evaluation the authors used the documents of the i2b2 Obesity Challenge and
      adopted its evaluation measures: F(1)-macro and F(1)-micro for measurements.
      RESULTS On the two subtasks of the Obesity Challenge (textual and intuitive
      classification) the system performed very well, and achieved a F(1)-macro = 0.80
      for the textual and F(1)-macro = 0.67 for the intuitive tasks, and obtained
      second place at the textual and first place at the intuitive subtasks of the
      challenge. CONCLUSIONS The authors show in the paper that a simple rule-based
      classifier can tackle the semantic classification task more successfully than
      machine learning techniques, if the training data are limited and some semantic
      labels are very sparse.

PMID- 19390102
TI  - A rule-based approach for identifying obesity and its comorbidities in medical
      discharge summaries.
AB  - OBJECTIVE Evaluate the effectiveness of a simple rule-based approach in
      classifying medical discharge summaries according to indicators for obesity and
      15 associated co-morbidities as part of the 2008 i2b2 Obesity Challenge. METHODS
      The authors applied a rule-based approach that looked for occurrences of
      morbidity-related keywords and identified the types of assertions in which those
      keywords occurred. The documents were then classified using a simple scoring
      algorithm based on a mapping of the assertion types to possible judgment
      categories. MEASUREMENTS RESULTS for the challenge were evaluated based on macro
      F-measure. We report micro and macro F-measure results for all morbidities
      combined and for each morbidity separately. Results Our rule-based approach
      achieved micro and macro F-measures of 0.97 and 0.77, respectively, ranking fifth
      out of the entries submitted by 28 teams participating in the classification task
      based on textual judgments and substantially outperforming the average for the
      challenge. CONCLUSIONS As shown by its ranking in the challenge results, this
      approach performed relatively well under conditions in which limited training
      data existed for some judgment categories. Further, the approach held up well in
      relation to more complex approaches applied to this classification task. The
      approach could be enhanced by the addition of expert rules to model more complex
      medical reasoning.

PMID- 19390103
TI  - Description of a rule-based system for the i2b2 challenge in natural language
      processing for clinical data.
AB  - The Obesity Challenge, sponsored by Informatics for Integrating Biology and the
      Bedside (i2b2), a National Center for Biomedical Computing, asked participants to
      build software systems that could "read" a patient's clinical discharge summary
      and replicate the judgments of physicians in evaluating presence or absence of
      obesity and 15 comorbidities. The authors describe their methodology and discuss
      the results of applying Lockheed Martin's rule-based natural language processing
      (NLP) capability, ClinREAD. We tailored ClinREAD with medical domain expertise to
      create assigned default judgments based on the most probable results as defined
      in the ground truth. It then used rules to collect evidence similar to the
      evidence that the human judges likely relied upon, and applied a logic module to
      weigh the strength of all evidence collected to arrive at final judgments. The
      Challenge results suggest that rule-based systems guided by human medical
      expertise are capable of solving complex problems in machine processing of
      medical text.

PMID- 19390104
TI  - Physicians' use of key functions in electronic health records from 2005 to 2007:
      a statewide survey.
AB  - OBJECTIVE Electronic health records (EHRs) have potential to improve quality and
      safety, but many physicians do not use these systems to full capacity. The
      objective of this study was to determine whether this usage gap is narrowing over
      time. DESIGN Follow-up mail survey of 1,144 physicians in Massachusetts who
      completed a 2005 survey. MEASUREMENTS Adoption of EHRs and availability and use
      of 10 EHR functions. RESULTS The response rate was 79.4%. In 2007, 35% of
      practices had EHRs, up from 23% in 2005. Among practices with EHRs, there was
      little change between 2005 and 2007 in the availability of nine of ten EHR
      features; the notable exception was electronic prescribing, reported as available
      in 44.7% of practices with EHRs in 2005 and 70.8% in 2007. Use of EHR functions
      changed inconsequentially, with more than one out of five physicians not using
      each available function regularly in both 2005 and 2007. Only electronic
      prescribing increased substantially: in 2005, 19.9% of physicians with this
      function available used it most or all the time, compared with 42.6% in 2007 (p <
      0.001). CONCLUSIONS By 2007, more than one third of practices in Massachusetts
      reported having EHRs; the availability and use of electronic prescribing within
      these systems has increased. In contrast, physicians reported little change in
      the availability and use of other EHR functions. System refinements,
      certification efforts, and health policies, including standards development,
      should address the gaps in both EHR adoption and the use of key functions.

PMID- 19390105
TI  - Seeking health information online: does Wikipedia matter?
AB  - OBJECTIVE To determine the significance of the English Wikipedia as a source of
      online health information. DESIGN The authors measured Wikipedia's ranking on
      general Internet search engines by entering keywords from MedlinePlus, NHS Direct
      Online, and the National Organization of Rare Diseases as queries into search
      engine optimization software. We assessed whether article quality influenced this
      ranking. The authors tested whether traffic to Wikipedia coincided with
      epidemiological trends and news of emerging health concerns, and how it compares
      to MedlinePlus. MEASUREMENTS Cumulative incidence and average position of
      Wikipedia compared to other Web sites among the first 20 results on general
      Internet search engines (Google, Google UK, Yahoo, and MSN, and page view
      statistics for selected Wikipedia articles and MedlinePlus pages. RESULTS
      Wikipedia ranked among the first ten results in 71-85% of search engines and
      keywords tested. Wikipedia surpassed MedlinePlus and NHS Direct Online (except
      for queries from the latter on Google UK), and ranked higher with quality
      articles. Wikipedia ranked highest for rare diseases, although its incidence in
      several categories decreased. Page views increased parallel to the occurrence of
      20 seasonal disorders and news of three emerging health concerns. Wikipedia
      articles were viewed more often than MedlinePlus Topic (p = 0.001) but for
      MedlinePlus Encyclopedia pages, the trend was not significant (p = 0.07-0.10).
      CONCLUSIONS Based on its search engine ranking and page view statistics, the
      English Wikipedia is a prominent source of online health information compared to
      the other online health information providers studied.

PMID- 19390106
TI  - Perceptions of standards-based electronic prescribing systems as implemented in
      outpatient primary care: a physician survey.
AB  - OBJECTIVE To compare the experiences of e-prescribing users and nonusers
      regarding prescription safety and workload and to assess the use of information
      from two e-prescribing standards (for medication history and formulary and
      benefit information), as they are implemented. DESIGN Cross-sectional survey of
      physicians who either had installed or were awaiting installation of one of two
      commercial e-prescribing systems. MEASUREMENTS Perceptions about medication
      history and formulary and benefit information among all respondents, and among e
      prescribing users, experiences with system usability, job performance impact, and
      amount of e-prescribing. RESULTS Of 395 eligible physicians, 228 (58%) completed
      the survey. E-prescribers (n = 139) were more likely than non-e-prescribers (n =
      89) to perceive that they could identify clinically important drug-drug
      interactions (83 versus 67%, p = 0.004) but not that they could identify
      prescriptions from other providers (65 versus 60%, p = 0.49). They also perceived
      no significant difference in calls about drug coverage problems (76 versus 71%
      reported getting 10 or fewer such calls per week; p = 0.43). Most e-prescribers
      reported high satisfaction with their systems, but 17% had stopped using the
      system and another 46% said they sometimes reverted to handwriting for
      prescriptions that they could write electronically. The volume of e-prescribing
      was correlated with perceptions that it enhanced job performance, whereas
      quitting was associated with perceptions of poor usability. CONCLUSIONS E
      prescribing users reported patient safety benefits but they did not perceive the
      enhanced benefits expected from using standardized medication history or
      formulary and benefit information. Additional work is needed for these standards
      to have the desired effects.

PMID- 19390107
TI  - Computerized clinical decision support during medication ordering for long-term
      care residents with renal insufficiency.
AB  - OBJECTIVE To determine whether a computerized clinical decision support system
      providing patient-specific recommendations in real-time improves the quality of
      prescribing for long-term care residents with renal insufficiency. DESIGN
      Randomized trial within the long-stay units of a large long-term care facility.
      Randomization was within blocks by unit type. Alerts related to medication
      prescribing for residents with renal insufficiency were displayed to prescribers
      in the intervention units and hidden but tracked in control units. Measurement
      The proportions of final drug orders that were appropriate were compared between
      intervention and control units within alert categories: (1) recommended
      medication doses; (2) recommended administration frequencies; (3) recommendations
      to avoid the drug; (4) warnings of missing information. RESULTS The rates of
      alerts were nearly equal in the intervention and control units: 2.5 per 1,000
      resident days in the intervention units and 2.4 in the control units. The
      proportions of dose alerts for which the final drug orders were appropriate were
      similar between the intervention and control units (relative risk 0.95, 95%
      confidence interval 0.83, 1.1) for the remaining alert categories significantly
      higher proportions of final drug orders were appropriate in the intervention
      units: relative risk 2.4 for maximum frequency (1.4, 4.4); 2.6 for drugs that
      should be avoided (1.4, 5.0); and 1.8 for alerts to acquire missing information
      (1.1, 3.4). Overall, final drug orders were appropriate significantly more often
      in the intervention units-relative risk 1.2 (1.0, 1.4). CONCLUSIONS Clinical
      decision support for physicians prescribing medications for long-term care
      residents with renal insufficiency can improve the quality of prescribing
      decisions. TRIAL REGISTRATION: http://clinicaltrials.gov Identifier: NCT00599209.

PMID- 19390108
TI  - Queuing theory to guide the implementation of a heart failure inpatient registry
      program.
AB  - OBJECTIVE The authors previously implemented an electronic heart failure registry
      at a large academic hospital to identify heart failure patients and to connect
      these patients with appropriate discharge services. Despite significant
      improvements in patient identification and connection rates, time to connection
      remained high, with an average delay of 3.2 days from the time patients were
      admitted to the time connections were made. Our objective for this current study
      was to determine the most effective solution to minimize time to connection.
      DESIGN We used a queuing theory model to simulate 3 different potential solutions
      to decrease the delay from patient identification to connection with discharge
      services. MEASUREMENTS The measures included average rate at which patients were
      being connected to the post discharge heart failure services program, average
      number of patients in line, and average patient waiting time. RESULTS Using
      queuing theory model simulations, we were able to estimate for our current system
      the minimum rate at which patients need to be connected (262 patients/mo), the
      ideal patient arrival rate (174 patients/mo) and the maximal patient arrival rate
      that could be achieved by adding 1 extra nurse (348 patients/mo). CONCLUSIONS Our
      modeling approach was instrumental in helping us characterize key process
      parameters and estimate the impact of adding staff on the time between
      identifying patients with heart failure and connecting them with appropriate
      discharge services.

PMID- 19390109
TI  - Medication administration errors in nursing homes using an automated medication
      dispensing system.
AB  - OBJECTIVE To identify the frequency of medication administration errors as well
      as their potential risk factors in nursing homes using a distribution robot.
      DESIGN The study was a prospective, observational study conducted within three
      nursing homes in the Netherlands caring for 180 individuals. MEASUREMENTS
      Medication errors were measured using the disguised observation technique. Types
      of medication errors were described. The correlation between several potential
      risk factors and the occurrence of medication errors was studied to identify
      potential causes for the errors. RESULTS In total 2,025 medication
      administrations to 127 clients were observed. In these administrations 428 errors
      were observed (21.2%). The most frequently occurring types of errors were use of
      wrong administration techniques (especially incorrect crushing of medication and
      not supervising the intake of medication) and wrong time errors (administering
      the medication at least 1 h early or late).The potential risk factors female
      gender (odds ratio (OR) 1.39; 95% confidence interval (CI) 1.05-1.83), ATC
      medication class antibiotics (OR 11.11; 95% CI 2.66-46.50), medication crushed
      (OR 7.83; 95% CI 5.40-11.36), number of dosages/day/client (OR 1.03; 95% CI 1.01
      1.05), nursing home 2 (OR 3.97; 95% CI 2.86-5.50), medication not supplied by
      distribution robot (OR 2.92; 95% CI 2.04-4.18), time classes "7-10 am" (OR 2.28;
      95% CI 1.50-3.47) and "10 am-2 pm" (OR 1.96; 1.18-3.27) and day of the week
      "Wednesday" (OR 1.46; 95% CI 1.03-2.07) are associated with a higher risk of
      administration errors. CONCLUSIONS Medication administration in nursing homes is
      prone to many errors. This study indicates that the handling of the medication
      after removing it from the robot packaging may contribute to this high error
      frequency, which may be reduced by training of nurse attendants, by automated
      clinical decision support and by measures to reduce workload.

PMID- 19390110
TI  - What evidence supports the use of computerized alerts and prompts to improve
      clinicians' prescribing behavior?
AB  - Alerts and prompts represent promising types of decision support in electronic
      prescribing to tackle inadequacies in prescribing. A systematic review was
      conducted to evaluate the efficacy of computerized drug alerts and prompts
      searching EMBASE, CINHAL, MEDLINE, and PsychINFO up to May 2007. Studies
      assessing the impact of electronic alerts and prompts on clinicians' prescribing
      behavior were selected and categorized by decision support type. Most alerts and
      prompts (23 out of 27) demonstrated benefit in improving prescribing behavior
      and/or reducing error rates. The impact appeared to vary based on the type of
      decision support. Some of these alerts (n = 5) reported a positive impact on
      clinical and health service management outcomes. For many categories of
      reminders, the number of studies was very small and few data were available from
      the outpatient setting. None of the studies evaluated features that might make
      alerts and prompts more effective. Details of an updated search run in Jan 2009
      are included in the supplement section of this review.

PMID- 19390111
TI  - Evaluation of a physician informatics tool to improve patient handoffs.
AB  - OBJECTIVE To facilitate patient handoffs between physicians, the computerized
      patient handoff tool (PHT) extracts information from the electronic health record
      to populate a form that is printed and given to the cross-cover physician.
      OBJECTIVES were to: (1) evaluate the rate at which data elements of interest were
      extracted from the electronic health record into the PHT, (2) assess the
      frequency for needing information beyond that contained in the PHT and where
      obtained, (3) assess physician's perceptions of the PHT, (4) identify
      opportunities for improvement. DESIGN Observational study. MEASUREMENTS This
      multi-method study included content coding of PHT forms, end of shift surveys of
      cross-cover resident physicians, and semi-structured interviews to identify
      opportunities for improvement. Thirty-five of 42 internal medicine resident
      physicians participated. Measures included: 1264 PHT forms coded for type of
      information, 63 end-of-shift surveys of cross-cover residents (residents could
      participate 2 times), and 18 semi-structured interviews. RESULTS For objective 1,
      patient identifiers and medications were reliably extracted (>98%). Other types
      of information-allergies and code status-were more variable (<50%). For objective
      2, nearly a quarter of respondents required information from physician notes not
      available in the PHT. For objective 3, respondents found that the PHT supported
      handoffs but indicated that it often excluded the assessment and plan. For
      objective 4, residents suggested including treatment plans. CONCLUSIONS The PHT
      reliably extracts information from the electronic health record. Respondents
      found the PHT to be suitable, although opportunities for improvement were
      identified.

PMID- 19390112
TI  - A systematic review of patient acceptance of consumer health information
      technology.
AB  - A systematic literature review was performed to identify variables promoting
      consumer health information technology (CHIT) acceptance among patients. The
      electronic bibliographic databases Web of Science, Business Source Elite, CINAHL,
      Communication and Mass Media Complete, MEDLINE, PsycArticles, and PsycInfo were
      searched. A cited reference search of articles meeting the inclusion criteria was
      also conducted to reduce misses. Fifty-two articles met the selection criteria.
      Among them, 94 different variables were tested for associations with acceptance.
      Most of those tested (71%) were patient factors, including sociodemographic
      characteristics, health- and treatment-related variables, and prior experience or
      exposure to computer/health technology. Only ten variables were related to human
      technology interaction; 16 were organizational factors; and one was related to
      the environment. In total, 62 (66%) were found to predict acceptance in at least
      one study. Existing literature focused largely on patient-related factors. No
      studies examined the impact of social and task factors on acceptance, and few
      tested the effects of organizational or environmental factors on acceptance.
      Future research guided by technology acceptance theories should fill those gaps
      to improve our understanding of patient CHIT acceptance, which in turn could lead
      to better CHIT design and implementation.

PMID- 19390114
TI  - Retraction: Correlation between DNA repair capacity in lymphocytes and acute side
      effects to skin during radiotherapy in nasopharyngeal cancer patients.

PMID- 19390113
TI  - The impact of computerized provider order entry systems on inpatient clinical
      workflow: a literature review.
AB  - Previous studies have shown the importance of workflow issues in the
      implementation of CPOE systems and patient safety practices. To understand the
      impact of CPOE on clinical workflow, we developed a conceptual framework and
      conducted a literature search for CPOE evaluations between 1990 and June 2007.
      Fifty-one publications were identified that disclosed mixed effects of CPOE
      systems. Among the frequently reported workflow advantages were the legible
      orders, remote accessibility of the systems, and the shorter order turnaround
      times. Among the frequently reported disadvantages were the time-consuming and
      problematic user-system interactions, and the enforcement of a predefined
      relationship between clinical tasks and between providers. Regarding the
      diversity of findings in the literature, we conclude that more multi-method
      research is needed to explore CPOE's multidimensional and collective impact on
      especially collaborative workflow.

PMID- 19390115
TI  - An extra double-stranded RNA binding domain confers high activity to a squid RNA
      editing enzyme.
AB  - RNA editing by adenosine deamination is particularly prevalent in the squid
      nervous system. We hypothesized that the squid editing enzyme might contain
      structural differences that help explain this phenomenon. As a first step, a
      squid adenosine deaminase that acts on RNA (sqADAR2a) cDNA and the gene that
      encodes it were cloned from the giant axon system. PCR and RNase protection
      assays showed that a splice variant of this clone (sqADAR2b) was also expressed
      in this tissue. Both versions are homologous to the vertebrate ADAR2 family.
      sqADAR2b encodes a conventional ADAR2 family member with an evolutionarily
      conserved deaminase domain and two double-stranded RNA binding domains (dsRBD).
      sqADAR2a differs from sqADAR2b by containing an optional exon that encodes an
      "extra" dsRBD. Both splice variants are expressed at comparable levels and are
      extensively edited, each in a unique pattern. Recombinant sqADAR2a and sqADAR2b,
      produced in Pichia pastoris, are both active on duplex RNA. Using a standard 48-h
      protein induction, both sqADAR2a and sqADAR2b exhibit promiscuous self-editing;
      however, this activity is particularly robust for sqADAR2a. By decreasing the
      induction time to 16 h, self-editing was mostly eliminated. We next tested the
      ability of sqADAR2a and sqADAR2b to edit two K+ channel mRNAs in vitro. Both
      substrates are known to be edited in squid. For each mRNA, sqADAR2a edited many
      more sites than sqADAR2b. These data suggest that the "extra" dsRBD confers high
      activity on sqADAR2a.

PMID- 19390116
TI  - Gene regulation by sense-antisense overlap of polyadenylation signals.
AB  - We show here that expression of genes from convergent transcription units can be
      regulated by the formation of double-stranded RNA (dsRNA) in the region of
      overlapping polyadenylation signals. The model system employed is the mouse
      polyomavirus. The early and late genes of polyomavirus are transcribed from
      opposite strands of the circular viral genome. At early times after infection,
      the early genes are expressed predominantly. Late gene expression increases
      dramatically upon the onset of DNA replication, when a major defect in
      polyadenylation of the late primary transcripts generates multigenomic RNAs that
      are precursors to the mature late mRNAs. Embedded in these late pre-mRNAs are
      sequences complementary to the early RNAs that act to down-regulate early gene
      expression via A-to-I editing of dsRNAs. In this system, the defective
      polyadenylation, and consequently the production of multigenomic late RNAs,
      depends on the context, and perhaps also, on the A-to-I editing of the poly(A)
      signal that overlaps the 3'-end of early transcripts.

PMID- 19390117
TI  - Proteomics identification of azaspiracid toxin biomarkers in blue mussels,
      Mytilus edulis.
AB  - Azaspiracids are a class of recently discovered algae-derived shellfish toxins.
      Their distribution globally is on the increase with mussels being most widely
      implicated in azaspiracid-related food poisoning events. Evidence that these
      toxins were bound to proteins in contaminated mussels has been shown recently. In
      the present study characterization of these proteins in blue mussels, Mytilus
      edulis, was achieved using a range of advanced proteomics tools. Four proteins
      present only in the hepatopancreas of toxin-contaminated mussels sharing identity
      or homology with cathepsin D, superoxide dismutase, glutathione S-transferase Pi,
      and a bacterial flagellar protein have been characterized. Several of the
      proteins are known to be involved in self-defense mechanisms against xenobiotics
      or up-regulated in the presence of carcinogenic agents. These findings would
      suggest that azaspiracids should now be considered and evaluated as potential
      tumorigenic compounds. The presence of a bacterial protein only in contaminated
      mussels was an unexpected finding and requires further investigation. The
      proteins identified in this study should assist with development of urgently
      required processes for the rapid depuration of azaspiracid-contaminated
      shellfish. Moreover they may serve as early warning indicators of shellfish
      exposed to this family of toxins.

PMID- 19390119
TI  - Metformin in renal failure--weigh the evidence.

PMID- 19390118
TI  - 5-Lipoxygenase-mediated endogenous DNA damage.
AB  - Lipoxygenases (LOs) convert polyunsaturated fatty acids into lipid
      hydroperoxides. Homolytic decomposition of lipid hydroperoxides gives rise to
      endogenous genotoxins such as 4-oxo-2(E)-nonenal, which cause the formation of
      mutagenic DNA adducts. Chiral lipidomics analysis was employed to show that a 5
      LO-derived lipid hydroperoxide was responsible for endogenous DNA-adduct
      formation. The study employed human lymphoblastoid CESS cells, which expressed
      both 5-LO and the required 5-LO-activating protein (FLAP). The major lipid
      peroxidation product was 5(S)-hydroperoxy-6,8,11,14-(E,Z,Z,Z)-eicosatetraenoic
      acid, which was analyzed as its reduction product, 5(S)-hydroxy-6,8,11,14
      (E,Z,Z,Z)-eicosatetraenoic acid (5(S)-HETE)). Concentrations of 5(S)-HETE
      increased from 0.07 +/- 0.01 to 45.50 +/- 4.05 pmol/10(7) cells upon stimulation
      of the CESS cells with calcium ionophore A23187. There was a concomitant increase
      in the 4-oxo-2(E)-nonenal-derived DNA-adduct, heptanone-etheno-2'-deoxyguanosine
      (HepsilondGuo) from 2.41 +/- 0.35 to 6.31 +/- 0.73 adducts/10(7) normal bases.
      Biosynthesis of prostaglandins, 11(R)-hydroxy-5,8,12,14-(Z,Z,E,Z)
      eicosatetraenoic acid, and 15(R,S)-hydroxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic
      acid revealed that there was cyclooxygenase (COX) activity in the CESS cells.
      Western blot analysis revealed that COX-1 was expressed by the cells, but there
      was no COX-2 or 15-LO-1. FLAP inhibitor reduced HepsilondGuo-adducts and 5(S)
      HETE to basal levels. In contrast, aspirin, which had no effect on 5(S)-HETE,
      blocked the formation of prostaglandins, 15-HETE, and 11-HETE but did not inhibit
      HepsilondGuo-adduct formation. These data showed that 5-LO was the enzyme
      responsible for the generation of the HepsilondGuo DNA-adduct in CESS cells.

PMID- 19390120
TI  - Survival and dialysis initiation: comparing British Columbia and Scotland
      registries.
AB  - BACKGROUND: Outcomes are a major metric for evaluating effectiveness of dialysis.
      Comparisons between different populations reveal significant variation. In
      addition, the question of optimal timing of dialysis start lacks robust data from
      which to generate conclusions. METHODS: This study compares dialysis survival in
      two geographically similar areas, Scotland and British Columbia, Canada (BC). The
      effect of eGFR at dialysis start on survival was also measured. Incident adult
      dialysis populations of Scotland (n = 3372) and BC (n = 3927), 2000-05 were
      compared. Mortality Hazard ratios (HR) were calculated using a Cox proportional
      hazards model. Multivariate analysis included pre-dialysis eGFR, registry, age,
      sex, dialysis modality, year of start, pre-dialysis haemoglobin and primary renal
      diagnosis. RESULTS: Median survival times from start of dialysis were 38 (35-40)
      and 44 (42-47) months in Scotland and BC, respectively, giving an unadjusted
      mortality HR, Scotland versus BC, of 1.20 (95% C.I. 1.12-1.29). BC patients
      started dialysis at a higher eGFR (8.9 ml/min/1.73 m(2)) than Scotland (7.5
      ml/min/1.73 m(2)), and prior to modelling higher starting eGFR was associated
      with higher mortality (1 ml/min/1.73 m(2) increase, HR = 1.028; 95% C.I. 1.021
      1.035). BC patients were also older and had more diabetic renal disease. In
      multivariate analysis, lower starting eGFR was associated with better survival,
      and Scotland had greater mortality than BC. General population mortality and
      transplantation rate had only minor influence. CONCLUSIONS: Concepts of 'late'
      versus 'early' start dialysis based on eGFR alone may need modification given the
      complexity and confounding reasons for dialysis initiation.

PMID- 19390121
TI  - An open pilot study of the efficacy and safety of Polygeline in adult subjects
      with dengue haemorrhagic fever.
AB  - AIM: To observe the efficacy and safety of Polygeline colloid (Haemaccel) in
      adults with stage I - II of dengue haemorrhagic fever (DHF). METHODS: An open,
      non-comparative clinical trial. The subjects were male or female between 17 - 55
      years old, who fulfilled the criteria of stage I or II of DHF according to WHO
      and selected with consecutive sampling. Fluid treatments were given following
      this protocol: polygeline i.v. infusion: 500 ml over first 6 hours and continued
      with 500 ml for the next 18 hours, and maintained to 1000 mL/24 hours from day-2
      until maximum day-5. Ringer's lactate infusion: 1000 mL/18 hours from the first
      day to maximum day-5, as maintenance. Efficacy and safety of polygeline colloid
      were evaluated using initial stabilization of haematocrite level, measured as
      percentage of clinical trial subject who has stabilization of haemodynamic status
      based on serial haematocrite levels examinations, total parenteral fluid required
      and length of hospitalization. Statisticial analysis was done using ANOVA test
      and post hoc analysis using Turkey test. RESULTS: There were 43 subjects who
      completely participated in this study and included in analysis. From baseline
      levels, haematocrite decreased in first 6 hours during fluid treatment. This
      decrement persisted in 48 hours of observation. Statistical analysis with ANOVA
      test showed the significant differences of haematocrite level during observation
      (Sum of square between groups 495 and within group 4845, p= 0.000). Post hoc
      analysis with Turkey test showed significant differences of haematocrite level
      from baseline level to 48, 72 and 96 hours during observation periods.
      CONCLUSION: This pilot study showed that polygeline colloid was a safe initial
      fluid treatment and can be used for maintaining fluid adequacy in adults with
      stage I-II of DHF.

PMID- 19390122
TI  - The difference between mean plasma levels of von Willebrand factor and platelet
      aggregation in type 2 diabetes mellitus with and without peripheral vascular
      disease at Sardjito General Hospital, Yogyakarta.
AB  - AIM: To determine the differences in mean plasma values of von Willebrand factor
      and platelet aggregation in type 2 DM patient with or without peripheral arterial
      disease. METHODS: This is a cross-sectional study, conducted from August to
      December 2006, in Dr. Sardjito General Hospital Yogyakarta, on type 2 DM
      patients, aged 50 years and above, and signed the informed consent. The exclusion
      criteria are cardiac failure, renal insufficiency (creatinine clearance <30
      ml/minute), malignancy, acute disease, decrease hepatic function, having ulcer or
      DM gangrene, amputation, taking multivitamine and/or antiplatelet, and smoking.
      All samples that matched inclusion criteria were divided into 2 groups: with
      peripheral arterial disease and without peripheral arterial disease. The data of
      subjects are presented as mean and standard deviation and proportion. Variables
      with numeric data are analized with the student t-test for normal distribution
      and with Mann-Whitney U-test for abnormal distribution. Significancy limit was
      set at p value of <0,05. Statistical analysis was done by using SPSS 11.5
      software. RESULTS: There were 17 subjects having PVD. There were no significantly
      differences of mean vWF plasma levels (140.544 + 76,137% vs. 133.325 + 53,246%)
      and platelet aggregation (87.741 + 19.886% vs. 93.981 + 10.138%) between type 2
      DM with and without PVD (p >0.05). CONCLUSION: There were no statistically
      difference in mean vWF plasma levels and platelet aggregation between type 2
      diabetes mellitus with and without PVD.

PMID- 19390123
TI  - The role of intensive insulin therapy in increasing superoxide dismutase (SOD)
      and normalizing hyperglycemia in critically ill patients.
AB  - AIM: To find out the difference between intensive insulin therapy and
      conventional insulin therapy in influencing the increase of superoxide dismutase
      (SOD), decrease of cytokine production (TNF-alpha and IL-6), increase of albumin
      level, and occurrence of SIRS. METHODS: The study design was randomized pre and
      post control group design involving 40 adult patients admitted to the ICU of
      Sanglah Hospital, Denpasar. The study subjects were randomly allocated into two
      groups: the first group to receive intensive insulin therapy in which blood
      glucose was set at a level between 80 - 110 mg/dL; the second group to receive
      conventional insulin therapy, which was given if the blood glucose level exceeded
      215 mg/dL and to be maintained at the level of between 180 - 200 mg/dL. RESULTS:
      This study showed: (1) There was a significant increase of SOD in the group
      receiving intensive insulin therapy as compared to the conventional insulin
      therapy (370.70 vs. 98.50 U/gHb, p=0.001), (2) There was no significant decrease
      in the TNF-alpha level, (3) There was a significant decrease of IL-6 level (10.25
      vs. 2.02; p=0.023); (4) There was a significant decrease in the event of SIRS
      (10% vs. 45%, p=0.000) in the intensive insulin therapy group as compared to the
      conventional insulin therapy group. CONCLUSION: Increase of insulin dose in the
      intensive insulin therapy can maintain blood glucose at normoglycemic level
      between 80 - 110 mg/dL faster than that in the conventional insulin therapy. On
      the other hand, intensive insulin therapy can increase the SOD level, decrease IL
      6 level, and decrease the events of SIRS in the ICU critically ill patients
      compared to conventional insulin therapy.

PMID- 19390124
TI  - Does insulin resistance correlate with routine blood examination? A review on
      erythrocytes of obese patients.
AB  - AIM: To identify whether hyperinsulinemia/insulin resistance affects the
      hematologic parameter of routine blood, especially the erythrocytes. METHODS:
      Cross sectional study was conducted on seventy one non-smoking obese patients who
      were not pregnant, not having lactating period, aged >22 years of age and visited
      the outpatient clinic of Endocrinology and outpatient clinic of Kidney and
      Hypertension division at the department of Internal Medicine Dr. Sardjito
      Hospital, Yogyakarta. Patients with cerebrovascular and blood disease; taking
      drugs affecting blood e.g.: cytostatics, and erythropoietin; and patients taking
      insulin, beta blocker, or steroids were excluded. Data on age, gender, body
      weight, and body height were recorded. Examinations on fasting blood glucose,
      fasting insulin, total cholesterol, triglycerides, high density lipoprotein
      (HDL), low density lipoprotein (LDL), and routine blood were performed in the
      condition of ten hours of fasting. All laboratory examination was conducted at
      Prodia Laboratory, Yogyakarta. RESULTS: Of seventy one obese patients, 51.5% were
      male, and 9.1% were diagnosed with diabetes mellitus (DM) during the study and
      the mean age was 47.09+5.74 years, the mean body mass index was 28.07+4.07
      kg/m(2), the mean of hemoglobin level was 13.75+1.57 g%; the mean of leukocyte
      count was 7.86+1.19 103/mm(3); erythrocytes count was 4.93+0.44 106/mm(3);
      platelet count 300.28+80.57 103/mm(3); and hematocrite count 41.23+4.28. There
      were very weak and statistically insignificant negative correlation between Log
      HOMA IR and erythrocytes (r= -0.048; p=0.693) CONCLUSION: This study demonstrates
      that insulin resistance has a very weak correlation with erythrocytes counts and
      it is statistically insignificant.

PMID- 19390125
TI  - Expression of NF-kappaB and COX-2 in young versus older patients with sporadic
      colorectal cancer.
AB  - AIM: To distinguish the expression of NF-kappaB and COX-2 between young and older
      group of sporadic colorectal cancer patients. METHODS: This was a comparative
      study between sporadic CRC patients aged 40 years or younger and patients aged 60
      years or more. Expression of NF-kappaB and COX-2 were assessed by
      immunohistochemical method using rabbit polyclonal antibodies against human p65
      NF-kappaB and COX-2 proteins. RESULTS: There were 98 cases of sporadic colorectal
      cancers between 1999 and 2007 obtained from the Department of Anatomical
      Pathology, Faculty of Medicine University of Indonesia, Jakarta and Department of
      Anatomical Pathology, Faculty of Medicine Padjajaran University, Bandung. There
      were 60 patients aged 60 years or more and 38 patients aged 40 years or less.
      Most tumors were located in the distal colon. Positive expression of NF-kappaB
      was found in 72 (73.5%) cases, whereas COX-2 expression was found in 48 (49.0%)
      cases. No significant difference of NF-kappaB and COX-2 expression between young
      and older patients. CONCLUSION: The expression of nuclear factor kappaB (NF
      kappaB) in Indonesian patients with sporadic colorectal cancer was high. However,
      cyclooxygenase-2 (COX-2) was only expressed in half of patients. There was no
      significant difference of NF-kappaB and COX-2 expressions between patients aged
      40 years or less and patients aged 60 years or more. Further studies are needed
      to elaborate the role of inflammation in sporadic colorectal carcinogenesis.

PMID- 19390126
TI  - Hanta virus infection during dengue virus infection outbreak in Indonesia.
AB  - AIM: To investigate which recent infection could have caused the present dengue
      like symptoms, in adult patients clinically fulfilling the WHO criteria for
      dengue, in which serologically were not confirmed for dengue virus infections.
      METHODS: Prospective study. During an outbreak of dengue (between May 1995 and
      May 1996) 118 consecutive adults (>13 years) suspected by the WHO 1997 case
      definition of DF or DHF were investigated. Patients were examined for history of
      illness, physical and laboratory findings consisting of full blood counts,
      prothrombin time (PT), activated partial thromboplastin time (aPTT), liver
      function (bilirubin, ASAT, ALAT), renal function (creatinine), and serological
      assays included dengue, hantavirus, chikungunya, R. typhi, R. tsutsugamuchi,
      rubella virus, influenza A virus, and leptospira. RESULTS: In 58 of the total 118
      patients, recent dengue virus infection was serologically confirmed. In 20 of the
      remaining 60 patients, we found serological evidence of another recent infection:
      hantavirus (5), chikungunya virus (2), R. typhi (5), R. tsutsugamuchi (2),
      rubella virus (3), influenza A virus (1), and leptospira (2). No evidence for
      recent infection with any of the mentioned agents was detected in the remaining
      40 specimens. CONCLUSION: We conclude that based on clinical characteristics
      alone, it is not easy to diagnose dengue. Specific laboratory tests to
      differentiate dengue from other febrile illnesses are needed. Among these, in
      Indonesia hantavirus infection should be considered as well.

PMID- 19390127
TI  - Pregnancy in a woman with uncorrected tetralogy of fallot.
AB  - Tetralogy of Fallot (ToF) is the most common form of cyanotic congenital heart
      disease after 1 year of age, with overall incidence approaching 10% of all
      congenital heart disease. Natural survival (i.e. without corrective procedure)
      into the fourth decade is extremely rare (only about 3%), but there is a tendency
      of increasing number of women with cyanotic congenital heart disease living 3 to
      4 decades and are becoming pregnant. Because of significant physiology adaptation
      and changes, pregnancy and delivery process are troublesome for mostly unhealthy
      women, including those with uncorrected ToF. For ToF patients, it remains an
      important cause of maternal morbidity (62,5%), and even mortality (10%) and has
      significant effects on fetal outcome. Discussed below a case of pregnancy in a 28
      year old woman with uncorrected ToF, was diagnosed to have pneumonia, ToF-class
      III-IV of New York Heart Association, secondary polycythemia caused by hypoxia,
      and uncompensated metabolic acidosis on 25th week pregnancy. Through delicate
      medical care, patient's condition improvement can be seen. Patient decided to
      continue the pregnancy. Without optimal either obstetrical or medical management,
      prognosis of pregnancy in patient with uncorrected ToF is poor.

PMID- 19390128
TI  - Adrenal incidentaloma.
AB  - Adrenal Incidentaloma is an adrenal tumor, which is unidentified before the
      imaging procedures conducted for an abnormality which is initially unforeseen as
      an adrenal disease. Symptoms and/or clinical signs of adrenal tumor do not have
      to be present prior to a diagnosis. Adrenal Incidentaloma can be divided into non
      hypersecreting adrenal adenoma, hypersecreting tumor, primary adrenal carcinoma,
      other adrenal mass, and metastases. The majority of adrenal tumor is non
      hypersecreting adrenal adenoma, but it is always considered as hypersecreting
      tumor until proven otherwise. Some conditions that can be found due to hormonal
      activity of adrenal incidentaloma is subclinical Cushing's syndrome,
      pheochromocytoma, aldosteronoma (Conn's disease), and several tumors which
      secrete androgen and sex hormone. Diagnostic approach of adrenal incidentaloma is
      focused on two main problems, which are, whether the lesion is hormonally active
      even though lacking characteristic clinical signs, and whether the lesion is
      benign or malignant; thus it needs hormonal and radiologic evaluation, even a
      fine needle biopsy. The management for adrenal incidentaloma includes surgical
      removal for hormonally active adrenal tumors, or inactive tumors with size less
      than 4 cm. Monitoring of tumor's hormone level and size are necessary for non
      hypersecreting tumor without surgical removal.

PMID- 19390129
TI  - Molecular mechanism on healing process of peptic ulcer.
AB  - Ulcer healing process is an intricate and active process including reconstruction
      process of mucosa through formation of granulation tissue. Granulation tissue
      formation takes place by means of formation of ulcer base, formation of blood
      vessel (angiogenesis) and re-establishment of glandular architecture. The process
      of granulation tissue formation on the ulcer base takes place 48-72 hours after
      ulceration process occurs. These three phases involve various genes grouped
      according to their activated time, i.e. the initial response genes, intermediate
      response gene and late response genes. Initial response genes are activated in 30
      minutes to 2 hours time, e.g EGF-R, c-fos, c-jun, egr-1, Sp-1, TFF-2/SP.
      Intermediate response genes are activated for 6 hours to 2 days, eg EGF, bFGF,
      PDGF and VEGF. Late response genes are activated for 14 days, e.g. HGF, ITF, c
      met/HGF-R.

PMID- 19390130
TI  - Gestational transient thyrotoxicosis.
AB  - Gestational transient thyrotoxicosis refers to non-autoimmune hyperthyroidism in
      pregnant women and it is associated with hyperemesis gravidarum. During
      pregnancy, there are some alterations in thyroid gland, such as elevation of
      thyroxine binding globulin, increased iodium clearance in kidneys, and
      stimulation of thyroid gland by human chorionic gonadotropin. Hitherto, the
      pathophysiology underlying the development of gestational transient
      thyrotoxicosis has not been fully recognized. Studies showed that human chorionic
      gonadotropin, an agonist of thyroid stimulating hormone, may stimulate thyroid
      stimulating hormone receptor, leading to increased thyroid hormone. Diagnosis of
      gestational transient thyrotoxicosis is established based on inexistence history
      of previous hyperthyroidism, elevation of thyroid hormone, absence of
      hyperthyroid abnormalities signs on physical examination (such as: enlargement of
      thyroid gland, exophthalmia), and the absent of positive thyroid autoantibody.
      Generally, gestational transient thyrotoxicosis does not require medication,
      unless if hyperemesis gravidarum is present, thus the patient has to be
      hospitalized to receive intravenous rehydration, electrolyte correction and
      antiemetic medication. On cases with worsened or prolonged symptoms, anti-thyroid
      agents such as short term propiltiourasil is needed.

PMID- 19390131
TI  - Function of the cell surface molecules (CD molecules) in the reproduction
      processes.
AB  - Recent studies brought the evidences that some cell surface molecules associated
      with immune system (cluster of differentiation (CD) molecules) may be involved in
      the fertilization process. The experimental observations regarding the function
      of CD9, CD49f/CD29, CD46 and CD11b/CD18 have led to the construction of general
      hypothesis of fertilization comprising the interaction of these CD molecules in
      binding and fusion of sperm and egg. The models for the role of CD9 and
      CD49f/CD29 in the fertilization are based on the interaction of tetraspanin CD9
      and integrin alpha6beta1 (CD49f/CD29) via fertilin in sperm-egg binding and
      fusion. The model for the role of integrin CD11b/CD18 and CD46 in fertilization
      is based on the interaction of these two molecules through complement C3
      fragments which may serve as bridging ligands between sperm CD46 and oocyte
      CD11b/CD18 and facilitate apposition of the sperm inner acrosomal membrane with
      oolemma.

PMID- 19390132
TI  - Spectrum of DHCR7 mutations in Slovak patients with Smith-Lemli-Opitz syndrome
      and detection of common mutations by PCR-based assays.
AB  - The Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive disorder associated
      with multiple developmental malformations, is caused by a large spectrum of
      mutations in the DHCR7 gene. Mutations in the DHCR7 gene lead to a 7
      dehydrocholesterol reductase deficiency, which is the final enzyme in the pathway
      of the cholesterol biosynthesis. Reduced cholesterol levels and elevated
      concentrations of its precursor 7-dehydrocholesterol in plasma and tissues are
      the major biochemical hallmarks of this disorder. In all patients a biochemical
      analysis of blood sterols using the gas chromatography/mass spectrometry was
      performed to confirm the clinical diagnosis of SLOS. We have also determined the
      mutational spectrum of DHCR7 gene in 17 Slovak patients. We identified six
      different mutations: nonsense mutation W151X and missense mutations V326L, L109P,
      G410S, R352Q, Y432C. Mutations W151X and V326L accounted for 76% of the SLOS
      alleles in Slovak population. The Slovak mutational spectrum is similar to that
      observed in other Central European countries. We also report simple polymerase
      chain reaction (PCR)-based assays that allow efficient and rapid mutation
      analysis.

PMID- 19390133
TI  - The correlation between the plasma nitric oxide levels and QT/QTc interval in
      conscious rabbits.
AB  - The current study was undertaken to investigate the effects of NOx (plasma
      concentrations of nitrate plus nitrite which are plasma nitric oxide (NO)
      metabolites) over QT interval and to determine the level of correlation between
      them in conscious rabbits. For this purpose, twenty-one New Zealand rabbits (5-7
      months old) were used and randomly assigned into the following three groups:
      control (CG; n = 7, 1 ml isotonic NaCl solution per animal/day), L-arginine (ARG
      G; n = 7, L-arginine solution 200 mg/kg/day) and L-NAME (NAME-G; n = 7, L-NAME
      solution 100 mg/kg/day). Injections were performed intraperitoneally at 9:00 a.m.
      for 9 days. Blood samples were collected 2 h after the injections on day 1, 5 and
      9 and the concentration of plasma NOx was determined using a colorimetric method.
      ECG was also recorded 2 h after the injection on 1st, 5th and 9th days. The heart
      rate, QT intervals, corrected QT intervals (QTc) and QT dispersion (QTd), QTc
      dispersion (QTcd) values were calculated from the ECG recordings. Statistically
      significant differences were observed between HR, QT and QTc values in all groups
      for all days (p < 0.001). QTd and QTcd values were found statistically
      significant different in NAME-G compared to CG and ARG-G (p < 0.001). It was also
      determined that there was a statistically significant correlation between the NOx
      and HR and QT and QTc in all days. It is concluded from this study that NO is an
      important molecule for the electrical activation of heart and has effects on the
      duration of QT/QTc interval, which should be taken into consideration by the
      physicians. In addition, application of the L-arginine should be further studied.

PMID- 19390134
TI  - Evaluation of remodeling in left and right ventricular myocytes from heterozygous
      (mRen2)27 transgenic rats.
AB  - Cardiac remodeling was assessed both in the pressure-overloaded left ventricle
      and in the normotensive right ventricle of hypertensive transgenic rats (mRen2)27
      (TGR27). The present study combined histology, electrophysiology, molecular
      biology and biochemistry techniques. A significant increase in action potential
      (AP) duration was recorded both in right and left ventricular myocytes wheareas
      only in the latter ones were hypertrophic. The increase in AP duration is mainly
      supported by the reduction of the transient outward K current (I(to)) density
      since no significant modification was observed for the L-type calcium current
      (I(Ca,L)), the sodium-calcium exchange current (I(NCX)), the delayed rectifier
      current (I(K)) and the inward rectifier current (I(K1)). The lower amplitude of
      I(to) current was associated with a lower Kv4.3 protein expression both in right
      and left ventricles while Kv4.3 mRNA levels was decreased only in left ventricle.
      Thus, a differential ventricular remodeling takes place in the TGR27 model. The
      possible cause of electrical remodeling in right ventricular myocytes of TGR27 is
      discussed.

PMID- 19390135
TI  - Acute diabetes mellitus and its influence on renal Na,K-ATPase in both genders.
AB  - Due to the importance of renal Na,K-ATPase in maintaining the sodium homeostasis
      in the organism, its activity and abundance is intensively studied in condition
      of diabetes mellitus. The main subject of this study was the investigation of
      properties of renal Na,K-ATPase and abundance of its alpha1 subunit in view of
      possible gender-dependent differences in male and female diabetic rats. Diabetes
      was induced by a single intraperitoneal dose of streptozotocin in a dose of 65
      mg.kg(-1). The acute diabetes lasting 8 days induced a significant increase in
      Na,K-ATPase activity accompanied by significant gender specific increase in K(m)
      value indicating a worsened affinity of ATP-binding site in female rats. In
      addition, our present experiments, revealed a significantly higher abundance of
      renal Na,K-ATPase alpha1 subunit in diabetic rats of both genders amounting 94%
      increase in males and 107% in females. But, not all of the newly synthesized
      enzyme molecules are fully active, as the increase in the number of active
      molecules is smaller (representing 23% in males and 20% in females) as indicated
      by lower increase in V(max) values.

PMID- 19390136
TI  - Protein oxidation under extremely low frequency electric field in guinea pigs.
      Effect of N-acetyl-L-cysteine treatment.
AB  - Modern age exposes humans to an increasing level of electromagnetic activity in
      their environment due to overhead power lines and transformers around residential
      areas. Studies have shown that treatment with antioxidants can suppress the
      oxidative damage induced by electromagnetic fields in various frequencies of the
      non-ionizing radiation band. In this study, we detected protein carbonyl content
      (PCO), advanced oxidation protein products (AOPP) in liver and 3-nitrotyrosine (3
      NT) levels in plasma of guinea pigs in order to investigate the effects of N
      acetyl-L-cysteine (NAC) administration on oxidative protein damage induced by
      power frequency electric (E) field (50 Hz, 12 kV/m, 7 days/8 h/day). We also
      analyzed hepatic hydroxyproline level to study protein synthesis. According to
      the findings of the present study, no statistically significant changes occurred
      in PCO, AOPP and 3-NT levels of the guinea pigs that were exposed to the E field
      with respect to the control group. However, liver hydroxyproline level was
      significantly diminished in the E field exposure group compared to the control
      and PCO, hydroxyproline and 3-NT levels changed significantly in the NAC
      administrated groups.

PMID- 19390137
TI  - Comparison of in vitro chondrogenic potential of human mesenchymal stem cells
      derived from bone marrow and adipose tissue.
AB  - In the present work, the human bone marrow and adipose tissue-derived mesenchymal
      stem cells (MSCs) were isolated and expanded under in vitro condition. After
      their phenotypic analysis, the chondrogenic differentiation was induced by using
      of the three-dimensional culture system without supplementation of growth
      factors, and their chondrogenic potential was compared. Obtained results proved
      that both types of MSCs undergo the process of chondrogenic differentiation.
      Comparative analysis showed that chondrogenic potential of adipose tissue-derived
      MSCs was slightly decreased in comparison with bone marrow-derived MSCs. However,
      both evaluated MSCs may play important role in the cartilage tissue engineering.

PMID- 19390138
TI  - Membrane transport and apoptosis-related proteins in radiation-associated acute
      myeloid leukemia following the Chornobyl accident.
AB  - We report on the results of multidrug-resistance transporters (P-glycoprotein,
      LRP, and MDR1), and apoptosis-related proteins (Fas, Bcl-2, Bax, p53, and Bcl
      X(L)) expression analysis of 56 acute myeloid leukemia (AML) patients by flow
      cytometry. Of these, there were 21 persons exposed to ionizing radiation due to
      the Chornobyl accident with radiation-associated and 35 patients with spontaneous
      AML. Leukemic cells in patients with radiation-associated AML more often
      overexpressed antiapoptotic protein Bcl-2 (12/21 vs. 6/35, p < 0.005) and less
      often demonstrated expression of Fas receptor (12/21 vs. 30/35, p < 0.05).
      Moreover, leukemic cells were simultaneously Fas negative and Bcl-2 positive in 4
      out of 21 patients exposed to ionizing radiation but none of spontaneous cases
      had similar phenotype (p < 0.05). Patients with radiation-associated AML compared
      to spontaneous cases more often were P-glycoprotein positive (12/20 vs. 9/31, p <
      0.05). P-glycoprotein overexpression significantly correlated with the resistance
      of the disease to chemotherapy in patients with radiation-associated AML (p <
      0.05).

PMID- 19390139
TI  - Photodynamic activity of pyropheophorbide methyl ester and pyropheophorbide a in
      dimethylformamide solution.
AB  - Comparative spectroscopic study including the photosensitizers of
      pyropheophorbide methyl ester (PPME) and pyropheophorbide a (PPa) was performed
      to study their photodynamic activity. The investigated photosensitizers in a
      homogeneous system of dimethylformamide (DMF) are not photostable upon
      irradiation. The photobleaching efficiency of PPa is higher than that of PPME.
      Combining these results with the data obtained by measuring the singlet oxygen
      quantum yield and the hydroxyl group generation, it was revealed that the
      photobleaching efficiency could be correlated with the singlet oxygen quantum
      yield and the hydroxyl group production of the photosensitizer.

PMID- 19390140
TI  - Kinetic parameters for thermal inactivation of soluble peroxidase from needles of
      Serbian spruce Picea omorika (Pancic) Purkyne.
AB  - Thermal inactivation of peroxidase (POD) in an extract of Picea omorika (Pancic)
      Purkyne needles initiated by heat treatment was studied. This is the first study
      of this kind on a conifer species. Non-linear regression analysis was applied on
      the inactivation rate data, combining Mitscherlich and Arrhenius equations,
      treating time and temperature simultaneously as explaining variables. We
      determined the inactivation rate constant k, the Arrhenius energy of inactivation
      E and the remaining activity C(min) for the crude extract and for separated
      acidic and basic enzyme fractions, as well as for individual isoenzymes separated
      electrophoretically. A comparison of inactivation parameters for acidic and basic
      fractions shows that the thermal inactivation rate of the basic fraction is
      higher. The obtained value of inactivation energy for crude extract was between
      the values for acidic and basic isoenzyme fractions. One of the three analysed
      individual isoenzymes was characterised by a lower inactivation rate constant and
      higher inactivation energy. Another isoenzyme showed considerably higher level of
      remaining activity compared to the others, which identified it as the most
      resistant to high temperatures. The acquired values of Arrhenius energy of
      inactivation for POD in crude extract were intermediate, considering a range of
      POD values for various other plant species.

PMID- 19390141
TI  - The effect of an NO donor, pentaerythrityl tetranitrate, on biochemical,
      functional, and morphological attributes of cardiovascular system of
      spontaneously hypertensive rats.
AB  - The status of nitric oxide (NO) in spontaneously hypertensive rats (SHR) is
      unclear and its bioavailability may be affected by imbalance with reactive oxygen
      species. We studied cardiovascular effects of an NO donor, pentaerythrityl
      tetranitrate (PETN) in SHR. We used Wistar rats, SHR and SHR treated with PETN
      (200 mg/kg/day). After six weeks, myocardium and aorta from each group were taken
      for biochemical and iliac artery for functional and morphological study. Long
      term administration of PETN to SHR increased cGMP level in platelets and did not
      affect blood pressure. In myocardium, the therapy resulted in a decrease in
      cardiac hypertrophy and MDA level, and the increased antioxidant enzyme activity
      of superoxide dismutase (SOD) and glutathione peroxidase (GPx). In aorta, PETN
      decreased the NO-synthase activity and had no affect on the enzyme activities of
      SOD and GPx or on MDA level. In the iliac artery, the endothelium-dependent
      relaxation to acetylcholine was slightly improved and the maximum
      vasoconstriction to noradrenaline was decreased. Wall thickness, cross-sectional
      area, inner diameter, and wall thickness/ inner diameter measured after perfusion
      fixation (120 mmHg) were not affected. The small effect of PETN on cardiovascular
      system suggests that NO deficiency is probably not the main cause of pathological
      alterations in SHR.

PMID- 19390142
TI  - Morphofunctional characteristics of ACTH cells in middle-aged male rats after
      treatment with genistein.
AB  - The soybean phytoestrogen, genistein, is increasingly consumed as an alternative
      therapeutic for age-related diseases. The aim of this study was to examine the
      morphofunctional characteristics of adrenocorticotrophic (ACTH) cells and blood
      concentrations of ACTH in sham-operated, orchidectomized and genistein-treated
      orchidectomized, 16-month-old Wistar male rats. Genistein (10 mg/kg/day) was
      administered subcutaneously for three weeks, while the control groups received
      the vehicle alone. Orchidectomy and genistein treatment decreased the volume
      density of ACTH cells and reduced (p < 0.05) circulating ACTH concentrations in
      comparison with control groups. In conclusion, genistein modulated the
      morphofunctional features of ACTH cells and decreased blood ACTH levels.

PMID- 19390143
TI  - Electrospun composite poly(L-lactic acid)/tricalcium phosphate scaffolds induce
      proliferation and osteogenic differentiation of human adipose-derived stem cells.
AB  - Development of tissue-engineered bone constructs has recently focused on the use
      of electrospun composite scaffolds seeded with stem cells from various source
      tissues. In this study, we fabricated electrospun composite scaffolds consisting
      of beta-tricalcium phosphate (TCP) crystals and poly(L-lactic acid) (PLA) at
      varying loading levels of TCP (0, 5, 10, 20 wt%) and assessed the composite
      scaffolds' material properties and ability to induce proliferation and osteogenic
      differentiation of human adipose-derived stem cells (hASCs) in the presence of
      osteogenic differentiating medium. The electrospun scaffolds all exhibited a
      nonwoven structure with an interconnected porous network. With the addition of
      TCP, the fiber diameter increased with each treatment ranging from 503.39 +/-
      20.31 nm for 0 wt% TCP to 1267.36 +/- 59.03 nm for 20 wt% TCP. Tensile properties
      of the composite scaffolds were assessed and the overall tensile strength of the
      neat scaffold (0 wt% TCP) was 847 +/- 89.43 kPA; the addition of TCP
      significantly decreased this value to an average of 350.83 +/- 38.57 kPa. As the
      electrospun composite scaffolds degraded in vitro, TCP was released into the
      medium with the largest release occurring within the first 6 days. Human ASCs
      were able to adhere, proliferate and osteogenically differentiate on all scaffold
      combinations. DNA content increased in a temporal manner for each scaffold over
      18 days in culture although for the day 12 timepoint, the 10 wt% TCP scaffold
      induced the greatest hASC proliferation. Endogenous alkaline phosphatase activity
      was enhanced on the composite PLA/TCP scaffolds compared to the PLA control
      particularly by day 18. It was noted that at the highest TCP loading levels of 10
      and 20 wt%, there was a dramatic increase in the amount of cell-mediated
      mineralization compared to the 5 wt% TCP and the neat PLA scaffold. This work
      suggests that local environment cues provided by the biochemical nature of the
      scaffold can accelerate the overall osteogenic differentiation of hASCs and
      encourage rapid ossification.

PMID- 19390144
TI  - The effect of artificial accelerated weathering on the mechanical properties of
      maxillofacial polymers PDMS and CPE.
AB  - The effect of UVA-UVB irradiation on the mechanical properties of three different
      industrial types of polydimethylsiloxane and chlorinated polyethylene samples,
      used in maxillofacial prostheses, was investigated in this study. Mechanical
      properties and thermal analysis are commonly used to determine the structural
      changes and mechanical strength. An aging chamber was used in order to simulate
      the solar radiation and assess natural aging. Compression and tensile tests were
      conducted on a Zwick testing machine. Durometer Shore A hardness measurements
      were carried out in a CV digital Shore A durometer according to ASTM D 2240.
      Glass transition temperature was evaluated with a differential scanning
      calorimeter. Simple mathematical models were developed to correlate the measured
      properties with irradiation time. The effect of UVA-UVB irradiation on
      compressive behavior affected model parameters. Significant deterioration seems
      to occur due to irradiation in samples.

PMID- 19390145
TI  - Structure of rat odorant-binding protein OBP1 at 1.6 A resolution.
AB  - The nasal mucosa is a specialist interfacial region sandwiched between the
      olfactory system and the gaseous chemical milieu. In mammals and insects, this
      region is rich in odorant-binding proteins that are thought to aid olfaction by
      assisting mass transfer of the many different organoleptic compounds that make up
      the olfactory landscape. However, in mammals at least, our grasp on the exact
      function of odorant-binding proteins is tentative and better insight into the
      role of these proteins is warranted, not least because of their apparent
      significance in the olfactory systems of insects. Here, the crystal structure of
      rat odorant-binding protein 1 is reported at 1.6 A resolution. This protein is
      one of the best-characterized mammalian odorant-binding proteins and only the
      third such protein structure to be solved at high resolution. The protein was
      crystallized in the holo form and contains an unidentifiable ligand that is
      probably an artefact from the Pichia pastoris expression system. Comparisons are
      made between this structure and a modelled OBP1 structure produced using the
      crystal structure of aphrodisin as a template. Comparisons are also made between
      OBP1 and the other two rat OBP subtypes, for which crystallographic data are
      unavailable. Interestingly, we also show that OBP1 is monomeric, which is in
      contrast to its previous assignment.

PMID- 19390146
TI  - The F4 fimbrial chaperone FaeE is stable as a monomer that does not require self
      capping of its pilin-interactive surfaces.
AB  - Many Gram-negative bacteria use the chaperone-usher pathway to express adhesive
      surface structures, such as fimbriae, in order to mediate attachment to host
      cells. Periplasmic chaperones are required to shuttle fimbrial subunits or pilins
      through the periplasmic space in an assembly-competent form. The chaperones cap
      the hydrophobic surface of the pilins through a donor-strand complementation
      mechanism. FaeE is the periplasmic chaperone required for the assembly of the F4
      fimbriae of enterotoxigenic Escherichia coli. The FaeE crystal structure shows a
      dimer formed by interaction between the pilin-binding interfaces of the two
      monomers. Dimerization and tetramerization have been observed previously in
      crystal structures of fimbrial chaperones and have been suggested to serve as a
      self-capping mechanism that protects the pilin-interactive surfaces in solution
      in the absence of the pilins. However, thermodynamic and biochemical data show
      that FaeE occurs as a stable monomer in solution. Other lines of evidence
      indicate that self-capping of the pilin-interactive interfaces is not a mechanism
      that is conservedly applied by all periplasmic chaperones, but is rather a case
      specific solution to cap aggregation-prone surfaces.

PMID- 19390147
TI  - Structure of SRP14 from the Schizosaccharomyces pombe signal recognition
      particle.
AB  - The signal recognition particle (SRP) Alu domain has been implicated in
      translation elongation arrest in yeasts and mammals. Fission yeast SRP RNA is
      similar to that of mammals, but has a minimal Alu-domain RNA lacking two stem
      loops. The mammalian Alu-domain proteins SRP9 and SRP14 bind their cognate Alu
      RNA as a heterodimer. However, in yeasts, notably Saccharomyces cerevisiae, SRP14
      is thought to bind Alu RNA as a homodimer, the SRP9 protein being replaced by
      SRP21, the function of which is not yet clear. Structural characterization of the
      Schizosaccharomyces pombe Alu domain may thus help to identify the critical
      features required for elongation arrest. Here, the crystal structure of the SRP14
      subunit of S. pombe SRP (SpSRP14) which crystallizes as a homodimer, is
      presented. Comparison of the SpSRP14 homodimer with the known structure of human
      SRP9/14 in complex with Alu RNA suggests that many of the protein-RNA contacts
      centred on the conserved U-turn motif are likely to be conserved in fission
      yeast. Initial attempts to solve the structure using traditional selenomethionine
      SAD labelling failed. However, two As atoms originating from the cacodylate
      buffer were found to make cysteine adducts and strongly contributed to the
      anomalous substructure. These adducts were highly radiation-sensitive and this
      property was exploited using the RIP (radiation-damage-induced phasing) method.
      The combination of SAD and RIP phases yielded an interpretable electron-density
      map. This example will be of general interest to crystallographers attempting de
      novo phasing from crystals grown in cacodylate buffer.

PMID- 19390148
TI  - 1.8 A structure of murine GITR ligand dimer expressed in Drosophila melanogaster
      S2 cells.
AB  - Glucocorticoid-induced TNF receptor ligand (GITRL), a prominent member of the TNF
      superfamily, activates its receptor on both effector and regulatory T cells to
      generate critical costimulatory signals that have been implicated in a wide range
      of T-cell immune functions. The crystal structures of murine and human orthologs
      of GITRL recombinantly expressed in Escherichia coli have previously been
      determined. In contrast to all classical TNF structures, including the human
      GITRL structure, murine GITRL demonstrated a unique ;strand-exchanged' dimeric
      organization. Such a novel assembly behavior indicated a dramatic impact on
      receptor activation as well as on the signaling mechanism associated with the
      murine GITRL costimulatory system. In this present work, the 1.8 A resolution
      crystal structure of murine GITRL expressed in Drosophila melanogaster S2 cells
      is reported. The eukaryotic protein-expression system allows transport of the
      recombinant protein into the extracellular culture medium, thus maximizing the
      possibility of obtaining correctly folded material devoid of any folding/assembly
      artifacts that are often suspected with E. coli-expressed proteins. The S2 cell
      expressed murine GITRL adopts an identical ;strand-exchanged' dimeric structure
      to that observed for the E. coli-expressed protein, thus conclusively
      demonstrating the novel quaternary structure assembly behavior of murine GITRL.

PMID- 19390149
TI  - Structure of a fatty-acid-binding protein from Bacillus subtilis determined by
      sulfur-SAD phasing using in-house chromium radiation.
AB  - Sulfur single-wavelength anomalous dispersion (S-SAD) and halide-soaking methods
      are increasingly being used for ab initio phasing. With the introduction of in
      house Cr X-ray sources, these methods benefit from the enhanced anomalous
      scattering of S and halide atoms, respectively. Here, these methods were combined
      to determine the crystal structure of BsDegV, a DegV protein-family member from
      Bacillus subtilis. The protein was cocrystallized with bromide and low-redundancy
      data were collected to 2.5 A resolution using Cr Kalpha radiation. 17 heavy-atom
      sites (ten sulfurs and seven bromides) were located using standard methods. The
      anomalous scattering of some of the BsDegV S atoms and Br atoms was weak, thus
      neither sulfurs nor bromides could be used alone for structure determination
      using the collected data. When all 17 heavy-atom sites were used for SAD phasing,
      an easily interpretable electron-density map was obtained after density
      modification. The model of BsDegV was built automatically and a palmitate was
      found tightly bound in the active site. Sequence alignment and comparisons with
      other known DegV structures provided further insight into the specificity of
      fatty-acid selection and recognition within this protein family.

PMID- 19390150
TI  - The human ACC2 CT-domain C-terminus is required for full functionality and has a
      novel twist.
AB  - Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin
      resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical
      target. Although the enzyme is highly conserved amongst animals, only the yeast
      enzyme structure is available for rational drug design. The use of biophysical
      assays has permitted the identification of a specific C-terminal truncation of
      the 826-residue human ACC2 carboxyl transferase (CT) domain that is both
      functionally competent to bind inhibitors and crystallizes in their presence.
      This C-terminal truncation led to the determination of the human ACC2 CT domain
      CP-640186 complex crystal structure, which revealed distinctions from the yeast
      enzyme complex. The human ACC2 CT-domain C-terminus is comprised of three
      intertwined alpha-helices that extend outwards from the enzyme on the opposite
      side to the ligand-binding site. Differences in the observed inhibitor
      conformation between the yeast and human structures are caused by differing
      residues in the binding pocket.

PMID- 19390151
TI  - Crystallization of a pentapeptide-repeat protein by reductive cyclic pentylation
      of free amines with glutaraldehyde.
AB  - The pentapeptide-repeat protein EfsQnr from Enterococcus faecalis protects DNA
      gyrase from inhibition by fluoroquinolones. EfsQnr was cloned and purified to
      homogeneity, but failed to produce diffraction-quality crystals in initial
      crystallization screens. Treatment of EfsQnr with glutaraldehyde and the strong
      reducing agent borane-dimethylamine resulted in a derivatized protein which
      produced crystals that diffracted to 1.6 A resolution; their structure was
      subsequently determined by single-wavelength anomalous dispersion. Analysis of
      the derivatized protein using Fourier transform ion cyclotron resonance mass
      spectrometry indicated a mass increase of 68 Da per free amino group. Electron
      density maps about a limited number of structurally ordered lysines indicated
      that the modification was a cyclic pentylation of free amines, producing
      piperidine groups.

PMID- 19390152
TI  - Heterogeneity and dynamics in villin headpiece crystal structures.
AB  - The villin headpiece domain (HP67) is the C-terminal F-actin-binding motif that
      confers F-actin-bundling activity to villin, a component of the actin bundles
      that support the brush-border microvilli. It has been investigated extensively by
      both experimental and theoretical measurements. Our laboratory, for example, has
      determined both its NMR and its crystal structures. This study presents the
      structures of HP67 and its pH-stabilized mutant (H41Y) in a different crystal
      form and space group. For both constructs, two molecules are found in each
      asymmetric unit in the new space group P6(1). While one of the two structures
      (Mol A) is structurally similar to our previously determined structure (Mol X),
      the other (Mol B) has significant deviations, especially in the N-terminal
      subdomain, where lattice contacts do not appear to contribute to the difference.
      In addition, the structurally most different crystal structure, Mol B, is
      actually closer to the averaged NMR structure. Harmonic motions, as suggested by
      the B-factor profiles, differ between these crystal structures; crystal
      structures from the same space group share a similar pattern. Thus, heterogeneity
      and dynamics are observed in different crystal structures of the same protein
      even for a protein as small as villin headpiece.

PMID- 19390153
TI  - EDM-DEDM and protein crystal structure solution.
AB  - Electron-density modification (EDM) procedures are the classical tool for driving
      model phases closer to those of the target structure. They are often combined
      with automated model-building programs to provide a correct protein model. The
      task is not always performed, mostly because of the large initial phase error. A
      recently proposed procedure combined EDM with DEDM (difference electron-density
      modification); the method was applied to the refinement of phases obtained by
      molecular replacement, ab initio or SAD phasing [Caliandro, Carrozzini,
      Cascarano, Giacovazzo, Mazzone & Siliqi (2009), Acta Cryst. D65, 249-256] and was
      more effective in improving phases than EDM alone. In this paper, a novel fully
      automated protocol for protein structure refinement based on the iterative
      application of automated model-building programs combined with the additional
      power derived from the EDM-DEDM algorithm is presented. The cyclic procedure was
      successfully tested on challenging cases for which all other approaches had
      failed.

PMID- 19390154
TI  - Combining crystallographic information and an aspherical-atom data bank in the
      evaluation of the electrostatic interaction energy in an enzyme-substrate
      complex: influenza neuraminidase inhibition.
AB  - Although electrostatic interactions contribute only a part of the interaction
      energies between macromolecules, unlike dispersion forces they are highly
      directional and therefore dominate the nature of molecular packing in crystals
      and in biological complexes and contribute significantly to differences in
      inhibition strength among related enzyme inhibitors. In the reported study, a
      wide range of complexes of influenza neuraminidases with inhibitor molecules
      (sialic acid derivatives and others) have been analyzed using charge densities
      from a transferable aspherical-atom data bank. The strongest interactions of the
      residues are with the acidic group at the C2 position of the inhibitor (
      approximately -300 kJ mol(-1) for -COO(-) in non-aromatic inhibitors,
      approximately -120-210 kJ mol(-1) for -COO(-) in aromatic inhibitors and
      approximately -450 kJ mol(-1) for -PO(3)(2-)) and with the amino and guanidine
      groups at C4 ( approximately -250 kJ mol(-1)). Other groups contribute less than
      approximately 100 kJ mol(-1). Residues Glu119, Asp151, Glu227, Glu276 and Arg371
      show the largest variation in electrostatic energies of interaction with
      different groups of inhibitors, which points to their important role in the
      inhibitor recognition. The Arg292-->Lys mutation reduces the electrostatic
      interactions of the enzyme with the acidic group at C2 for all inhibitors that
      have been studied (SIA, DAN, 4AM, ZMR, G20, G28, G39 and BCZ), but enhances the
      interactions with the glycerol group at C6 for inhibitors that contain it. This
      is in agreement with the lower level of resistance of the mutated virus to
      glycerol-containing inhibitors compared with the more hydrophobic derivatives.

PMID- 19390155
TI  - The role of entropy and polarity in intermolecular contacts in protein crystals.
AB  - The integrity and X-ray diffraction quality of protein crystals depend on the
      three-dimensional order of relatively weak but reproducible intermolecular
      contacts. Despite their importance, relatively little attention has been paid to
      the chemical and physical nature of these contacts, which are often regarded as
      stochastic and thus not different from randomly selected protein surface patches.
      Here, logistic regression was used to analyze crystal contacts in a database of
      821 unambiguously monomeric proteins with structures determined to 2.5 A
      resolution or better. It is shown that the propensity of a surface residue for
      incorporation into a crystal contact is not a linear function of its solvent
      accessible surface area and that amino acids with low exposed surfaces, which are
      typically small and hydrophobic, have been underestimated with respect to their
      contact-forming potential by earlier area-based calculations. For any given
      solvent-exposed surface, small and hydrophobic residues are more likely to be
      involved in crystal contacts than large and charged amino acids. Side-chain
      entropy is the single physicochemical property that is most negatively correlated
      with the involvement of amino acids in crystal contacts. It is also shown that
      crystal contacts with larger buried surfaces containing eight or more amino acids
      have cores that are depleted of polar amino acids.

PMID- 19390156
TI  - ALINE: a WYSIWYG protein-sequence alignment editor for publication-quality
      alignments.
AB  - Marked-up sequence alignments typically provide the central figure in articles
      describing proteins, whether in the fields of biochemistry, bioinformatics or
      structural biology. The generation of these figures is often unwieldy:
      interactive programs are often aesthetically limited and the use of batch
      programs requires the repetitive iterative editing of scripts. ALINE is a
      portable interactive graphical sequence-alignment editor implemented in Perl/Tk
      which produces publication-quality sequence-alignment figures where "what you see
      is what you get". ALINE is freely available for download from
      http://crystal.bcs.uwa.edu.au/px/charlie/software/aline/.

PMID- 19390157
TI  - Is C-reactive protein a predictor of perioperative events before coronary artery
      bypass?

PMID- 19390158
TI  - Are treatment effects of ACEI and ARB in post-MI patients homogeneous?

PMID- 19390159
TI  - Oral carcinogenicity and toxicity of 2-amino-4-chlorophenol in rats.
AB  - OBJECTIVES: This study was carried out to clarify the subchronic and chronic
      toxicity, and carcinogenicity of 2-amino-4-chlorophenol(ACP). METHODS:
      Carcinogenicity, and chronic and subchronic toxicity of ACP were examined by
      feeding 10 rats of both sexes ACP-containing diet at a dose level of 0 (control),
      512, 1,280, 3,200, 8,000 or 20,000 ppm (w/w) for 13 wk and 50 rats of both sexes
      at a dose level of 0, 1,280, 3,200 or 8,000 ppm for 2 yr. RESULTS: The 13-wk oral
      subchronic toxicity of ACP was characterized by proliferative lesions leading to
      development of tumors in the forestomach and urinary bladder and by erythrocyte
      toxicity as evidenced by decreases in red blood cell counts, hemoglobin and
      hematocrit and concurrent increases in methemoglobin levels and reticulocyte
      counts. Both simple and papillary and/or nodular types of transitional cell
      hyperplasias were observed in the urinary bladder of ACP-fed male rats. The
      proliferative lesions appeared at higher doses of ACP after the 13-wk
      administration than clear erythrocyte toxicity did. The 2-yr oral administration
      of ACP significantly increased incidences of squamous cell papillomas and
      carcinomas in the forestomach of male and female rats and transitional cell
      carcinomas in the urinary bladder of male rats. These tumor incidences increased
      dose-dependently. Notably, clear signs of erythrocyte toxicity were not evident
      after the 2-yr administration of ACP. CONCLUSION: Clear evidence of carcinogenic
      activity of ACP was shown in male and female rats. These data might be useful for
      the health risk assessment of workers exposed to ACP.

PMID- 19390160
TI  - How job demands affect an intimate partner: a test of the spillover-crossover
      model in Japan.
AB  - OBJECTIVES: The present study examined how job demands affect an intimate
      partner's well-being. We hypothesized that job demands have a negative influence
      on partner well-being through the experience of work-family conflict (WFC) and an
      impaired quality of the relationship (reduced social support and increased social
      undermining towards the partner). METHODS: The participants of this study were 99
      couples of dual-earner parents in Japan. RESULTS: Consistent with hypotheses,
      men's job demands (i.e. overload and emotional demands) were positively related
      to their own reports of WFC, and indirectly to women's ratings of men's WFC.
      Consequently, women's ratings of men's WFC were negatively related to the quality
      of the relationship (i.e. decreased social support from and increased social
      undermining by men), which, in turn, led to women's ill-health (i.e. depressive
      symptoms and physical complaints). We found similar findings for the model
      starting with women's job demands; gender did not affect the strength of the
      relationships in the model. CONCLUSIONS: These findings suggest that high job
      demands initiate a process of work-family conflict and poor relationship quality,
      which may eventually affect the intimate partner's well-being in an unfavorable
      way.

PMID- 19390161
TI  - Pulmonary manifestations of Sjogren's syndrome.
AB  - BACKGROUND: Primary Sjogren's syndrome (PSS) is associated with various
      histological patterns of interstitial lung disease. Although chest images and
      lung function studies showed that lung involvement predominantly occurs in small
      airways, pathological findings were not consistent with the results of high
      resolution CT (HRCT) and lung function tests. OBJECTIVES: To investigate the
      pathological characteristics of PSS-associated interstitial lung disease (PSS
      ILD) and their relationship with HRCT lung function tests. METHODS: Fourteen
      patients diagnosed as PSS who underwent surgical lung biopsy in Peking Union
      Medical College Hospital from October 2000 to October 2006 were reviewed.
      Histopathologic findings, radiologic findings and lung function tests were
      analyzed. RESULTS: The study included 13 women. The median age was 46 years. Most
      patients presented with dyspnea and cough. CT scans revealed bilateral ground
      glass, consolidative, reticular and nodular opacities and cyst lesions. The
      histological patterns included nonspecific interstitial pneumonia (NSIP) cellular
      pattern associated with organizing pneumonia (OP), NSIP mixed pattern associated
      with OP, noncaseating granulomas, chronic bronchiolitis, follicular
      bronchiolitis, constrictive bronchiolitis, lymphocytic interstitial pneumonia
      associated with follicular bronchiolitis, NSIP mixed pattern associated with
      follicular bronchiolitis, NSIP mixed pattern coexisting with chronic
      bronchiolitis, OP associated with chronic bronchiolitis, and noncaseating
      granulomas coexisting with OP. Treatment included prednisone and
      cyclophosphamide. During the follow-up period (median 38 months), most patients
      improved or remained stable. The patient with constrictive bronchiolitis died
      from progression of primary disease. CONCLUSIONS: The histopathologic patterns of
      PSS-ILD included lung interstitial involvement and small airway involvement or
      both. Corticosteroid therapy combined with cyclophosphamide was administered with
      a favorable response in the majority of patients.

PMID- 19390162
TI  - CD4+ T cells and immunosenescence--a mini-review.
AB  - Age-related declines in immune function are associated with reduced humoral
      responses following vaccination or infection. Central to this defect is a decline
      in naive CD4+ T cell function. In this review, we discuss factors intrinsic and
      extrinsic to the CD4+ T cell compartment that affect host immunity and propose
      means by which deficient CD4+ T cell function can be fully restored in the aged.

PMID- 19390163
TI  - Changes in histomorphometric and mechanical properties of femurs induced by
      acupuncture at the Shenshu point in the SAMP6 mouse model of senile osteoporosis.
AB  - BACKGROUND/OBJECTIVE: The effect of acupuncture on the changes in the
      histomorphometric and mechanical properties of femurs in senescence-accelerated
      mice strain P6 (SAMP6) was evaluated in this work. METHODS: Six-month-old male
      SAMP6 and SAMR1 mice were allocated to 1 of 4 groups: SAMP6 control group (Pc),
      SAMP6 non-acupoint control group (Pn), SAMP6 acupuncture group (Pa) and SAMR1
      control group (Rc). The Pa group was acupunctured at the Shenshu point (BL23)
      once daily for 8 weeks. Two non-acupoints at the hypochondria were needled for
      the Pn group. Mice in the other 2 groups were grasped using the same method as
      for the Pa group. The serum testosterone and osteocalcin (OC) levels were
      determined by radioimmunoassay. The histomorphometric data were obtained from
      undecalcified specimens, and the mechanical properties of the femur were assessed
      by the 3-point bending test. RESULTS: After acupuncture treatment, the decreased
      serum testosterone level in SAMP6 mice increased markedly, whereas the increased
      OC concentration declined sharply. The bone histomorphometric and mechanical
      indexes of SAMP6 mice also improved significantly. The values of trabecular
      thickness, trabecular bone volume, osteoid volume, mineral apposition rate and
      bone formation rate in Pa mice increased by 20.4, 18.1, 14.1, 9.9 and 14.7%,
      respectively, compared with Pc mice. The scores for ultimate force, yield force,
      elastic stress, ultimate stress and energy to yield force for Pa mice were
      significantly higher than those of Pc and Pn mice. CONCLUSION: Therefore,
      acupuncture at BL23 was effective in promoting bone formation, restoring the
      amount of bone volume, improving bone architecture and reversing osteoporosis in
      SAMP6 mice to some degree by enhancing the secretion of testosterone and
      declining bone turnover.

PMID- 19390164
TI  - Secretion of fibrinolytic enzymes facilitates human mesenchymal stem cell
      invasion into fibrin clots.
AB  - Adult human mesenchymal stem cells (hMSC) are involved in wound healing and
      regeneration of mesodermal tissue, but the underlying homing mechanisms are not
      well understood. Fibrin clot formation is associated with most wound healing
      processes and potentially guides the recruitment of hMSC. The objective of this
      study is the investigation of a fibrinolytic capacity, which is required for hMSC
      to migrate into a wounded tissue and thus to contribute to tissue regeneration.
      Using RT-PCR, semiquantitative real-time PCR and ELISA, we detected key
      components of the fibrinolytic cascade, including the urokinase plasminogen
      activator (uPA) and its receptor (uPAR), the tissue plasminogen activator (tPA)
      and the plasminogen activator inhibitor (PAI), suggesting a strong fibrinolytic
      activity of hMSC. To test this activity in a functional assay, we cultured fibrin
      embedded hMSC in vitro for 7 days. The cells efficiently dissolved the
      surrounding fibrin mesh into the fibrin degradation products, the
      fibrinopeptides. The fibrinolytic activity of hMSC and human dermal fibroblasts,
      known to be critically involved in skin wound extracellular matrix remodeling,
      was similar. Our results suggest that a high intrinsic fibrinolytic capacity of
      hMSC mediates the invasion into a fibrin clot of a wounded tissue.

PMID- 19390165
TI  - Waist circumference values of Nigerian children and adolescents.
AB  - AIMS: This study aimed to determine the waist circumference (WC) of apparently
      healthy Nigerian children and adolescents and to compare the obtained values with
      available data for children from other parts of the world. METHODS: A
      representative sample of children from 7 schools in Abeokuta, a state capital in
      South West Nigeria, was selected using the multi-staged random sampling
      technique. The sample population consisted of 570 children with ages ranging from
      5 to 19 years. RESULTS: WC increased with age in both sexes. The mean value of WC
      of children aged 5-9 years was about the same in both sexes (p = 0.113). However,
      in children older than 9 years, females had higher WCs than males (p = 0.000).
      Comparison of the 50th percentile WC of Nigerian children with that of American
      and Spanish children showed that both Nigerian male and female children had the
      lowest WC values. However, the values were similar to British male children up to
      9 years and female children up to 14 years. CONCLUSION: The WC value varied with
      age, sex and race. These data are expected to serve as a baseline against which
      future data can be compared.

PMID- 19390166
TI  - Green tea (-)-epigallocatechin-3-gallate reduces body weight with regulation of
      multiple genes expression in adipose tissue of diet-induced obese mice.
AB  - AIMS: The aim of this study was to investigate the antiobesity effect of (-)
      epigallocatechin-3-gallate (EGCG) in diet-induced obese mice. METHODS: Male
      C57BL/6J mice were fed on a high-fat diet for 8 weeks to induce obesity.
      Subsequently they were divided into 3 groups and were maintained on a high-fat
      control diet or high-fat diets supplemented with 0.2 or 0.5% EGCG (w/w) for a
      further 8 weeks. Changes in the expression of genes related to lipid metabolism
      and fatty acid oxidation were analyzed in white adipose tissue, together with
      biometric and blood parameters. RESULTS: Experimental diets supplemented with
      EGCG resulted in reduction of body weight and mass of various adipose tissues in
      a dose-dependent manner. EGCG diet also considerably lowered the levels of plasma
      triglyceride and liver lipid. In the epididymal white adipose tissue of EGCG diet
      fed mice, the mRNA levels of adipogenic genes such as peroxisome proliferator
      activated receptor-gamma (PPAR-gamma), CCAAT enhancer-binding protein-alpha
      (C/EBP-alpha), regulatory element-binding protein-1c (SREBP-1c), adipocyte fatty
      acid-binding protein (aP2), lipoprotein lipase (LPL) and fatty acid synthase
      (FAS) were significantly decreased. However, the mRNA levels of carnitine
      palmitoyl transferase-1 (CPT-1) and uncoupling protein 2 (UCP2), as well as
      lipolytic genes such as hormone sensitive lipase (HSL) and adipose triglyceride
      lipase (ATGL), were significantly increased. CONCLUSION: These results suggest
      that green tea EGCG effectively reduces adipose tissue mass and ameliorates
      plasma lipid profiles in high-fat diet-induced obese mice. These effects might be
      at least partially mediated via regulation of the expression of multiple genes
      involved in adipogenesis, lipolysis, beta-oxidation and thermogenesis in white
      adipose tissue.

PMID- 19390167
TI  - Endothelial protective effects of anthocyanins: the underestimated role of their
      metabolites.

PMID- 19390168
TI  - Electro-acoustic stimulation of the cochlea. Editorial.

PMID- 19390169
TI  - Electro-acoustic stimulation. Acoustic and electric pitch comparisons.
AB  - For simultaneous acoustic and electric stimulation to be perceived as
      complementary, it may be beneficial for hearing aids and cochlear implants (CI)
      to be adjusted to provide compatible pitch sensations. To this end, estimates of
      the pitch perceived for a set of acoustic and electric stimuli were obtained from
      14 CI users who had usable low-frequency hearing, either in the non-implanted ear
      or in both ears. The subjects assigned numerical pitch estimates to each of 5
      acoustic pure tones and 5 single-electrode electric pulse trains. On average, the
      acoustic frequency that corresponded in pitch to stimulation on the most apical
      electrode was approximately 480 Hz. This was about 1 octave lower than the
      frequency expected from Greenwood's frequency-place function applied to estimates
      of the electrode insertion angle based on X-ray images. Furthermore, evidence was
      found suggesting that pitch decreased with increasing duration of CI use. Pitch
      estimates from 5 subjects who completed the experiment before experiencing any
      other sounds through their CI were generally close to the values expected from a
      recently published frequency map for the cochlear spiral ganglion. Taken
      together, these findings suggest that some perceptual adaptation may occur that
      would compensate in part for the apparent mismatch between the intracochlear
      position of the electrodes and the acoustic frequencies assigned to them in the
      sound processor.

PMID- 19390170
TI  - Impact of low-frequency hearing.
AB  - Today, cochlear implantation is the treatment of choice in the case of severe to
      profound hearing loss, but the speech perception abilities of many recipients in
      noisy conditions are still poor and the overall sound quality and ease of
      listening still require improvement. Residual low-frequency hearing has been
      associated with improved hearing performance in cochlear implant patients,
      especially in difficult listening environments (i.e. cocktail party effect). It
      seems that low-frequency information can enhance the segregation of competing
      voices, which leads to better speech understanding in noise. We investigated the
      effect of low-frequency hearing on speech perception performance in a group of
      subjects being implanted with the Nucleus Hybrid-L device. The Hybrid-L device is
      a modified Nucleus Freedom implant, which instead of the standard electrode
      carries a very delicate electrode array that allows preservation of residual
      hearing to a great extent. Sentence test results from 22 subjects are presented
      here. Additionally, for 8 subjects, the acoustically presented frequency range
      was limited to 300, 500 and 700 Hz, and speech perception tests with a single
      competing talker were conducted. The Hybrid-L study group achieved a speech
      reception threshold of 15.9 dB in the hearing aid alone condition, 10.8 dB in the
      cochlear implant alone condition, and 3.9 dB when using the combination of
      cochlear implant and hearing aid. Differences between the 3 conditions are
      statistically significant. Results from the additional experiment on the
      acoustically presented frequency range suggest that very limited residual hearing
      below 500 Hz is already sufficient to produce a significant improvement in speech
      perception performance in conjunction with a cochlear implant.

PMID- 19390171
TI  - How much residual hearing is 'useful' for music perception with cochlear
      implants?
AB  - AIM: To compare performance on a song recognition task of bilaterally combined
      electric and acoustic hearing (bimodal stimulation) with electric or acoustic
      hearing alone. METHODS: Subjects were 14 adults with cochlear implants (CI) who
      continued to use a hearing aid (HA) in one/both ears. Subjects were asked to
      identify excerpts from 15 popular songs, which were familiar to them, presented
      in a random order via a single loudspeaker. Presentation conditions were fixed in
      order: bimodal, CI alone and then HA alone. Musical excerpts were presented in
      each condition with and then without lyrics. RESULTS: In a subgroup of subjects
      (n = 8) with better low-frequency residual hearing (thresholds <85 dB hearing
      level (HL)), mean scores for bimodal stimulation were significantly greater than
      for CI alone. In addition, mean 'no lyrics' scores for HA alone (59.7%) were
      significantly greater than for CI alone (38.8%). All of these subjects considered
      bimodal stimulation to be the most enjoyable way to listen to music. For the
      remaining subjects (n = 6) there was no benefit from using bimodal stimulation
      over CI alone, and the majority of these preferred to listen to music using CI
      alone. CONCLUSIONS: Bimodal stimulation provides better perception of popular
      music, particularly melody recognition, compared to CI alone when low-frequency
      residual hearing is better than 85 dB HL.

PMID- 19390172
TI  - Hearing conservation surgery using the Hybrid-L electrode. Results from the first
      clinical trial at the Medical University of Hannover.
AB  - Patients with high-frequency deafness and/or substantial residual hearing across
      frequencies might benefit from combined electro-acoustic stimulation. The Hybrid
      L electrode was designed to address the issues of both hearing conservation and
      effective electrical stimulation in those recipients. The electrode with 22
      contacts should be inserted through the round window membrane, and covers
      approximately 270 degrees of the basal turn of the cochlear. This insertion
      length is equivalent to the one seen in many patients using the former Nucleus
      straight electrode. Twenty-four patients with low-frequency thresholds of 60 dB
      or better, up to 500 Hz, were implanted with a Hybrid-L device in a clinical
      trial at the Medical University of Hannover. Another group of 8 recipients with
      less residual hearing was included under extended inclusion criteria. Residual
      hearing was conserved in the majority of cases. One patient had a loss of more
      than 30 dB, but hearing partially recovered after 9 months. The median loss in
      all patients was 10 dB in both the Hybrid group and the extended group. Patients
      were able to use the residual hearing postoperatively to the same extent as
      preoperatively. In the Hybrid mode (cochlear implant + ipsilateral hearing aid),
      patients showed a significant improvement of 21% (p = 0.002) in speech
      understanding in quiet using the Freiburger Monosyllabic Word Test compared to
      the preoperative scores under aided conditions with their hearing aid. The
      Oldenburg Sentence Test in noise showed a remarkable average improvement of 10.2
      dB (p < 0.001) compared to the preoperative hearing aid only mode. An additional
      improvement could be seen in the combined mode using an additional contralateral
      hearing aid. Recipients with a shorter duration of high-frequency hearing loss
      showed a larger benefit than those with a longer duration of hearing loss.
      Hearing conservation using the Hybrid-L electrode and a given surgical technique
      is possible with high probability in patients with high-frequency deafness or
      pantonal hearing loss. The use of the residual acoustic hearing offers specific
      advantages, especially for understanding speech in noise and for spatial hearing.

PMID- 19390173
TI  - Hybrid 10 clinical trial: preliminary results.
AB  - Acoustic plus electric (electric-acoustic) speech processing has been successful
      in highlighting the important role of articulation information in consonant
      recognition in those adults that have profound high-frequency hearing loss at
      frequencies greater than 1500 Hz and less than 60% discrimination scores. Eighty
      seven subjects were enrolled in an adult Hybrid multicenter Food and Drug
      Administration clinical trial. Immediate hearing preservation was accomplished in
      85/87 subjects. Over time (3 months to 5 years), some hearing preservation was
      maintained in 91% of the group. Combined electric-acoustic processing enabled
      most of this group of volunteers to gain improved speech understanding, compared
      to their preoperative hearing, with bilateral hearing aids. Most have
      preservation of low-frequency acoustic hearing within 15 dB of their preoperative
      pure tone levels. Those with greater losses (>30 dB) also benefited from the
      combination of electric-acoustic speech processing. Postoperatively, in the
      electric-acoustic processing condition, loss of low-frequency hearing did not
      correlate with improvements in speech perception scores in quiet. Sixteen
      subjects were identified as poor performers in that they did not achieve a
      significant improvement through electric-acoustic processing. A multiple
      regression analysis determined that 91% of the variance in the poorly performing
      group can be explained by the preoperative speech recognition score and duration
      of deafness. Signal-to-noise ratios for speech understanding in noise improved
      more than 9 dB in some individuals in the electric-acoustic processing condition.
      The relation between speech understanding in noise thresholds and residual low
      frequency acoustic hearing is significant (r = 0.62; p < 0.05). The data suggest
      that, in general, the advantages gained for speech recognition in noise by
      preserving residual hearing exist, unless the hearing loss approaches profound
      levels. Preservation of residual low-frequency hearing should be considered when
      expanding candidate selection criteria for standard cochlear implants. Duration
      of profound high-frequency hearing loss appears to be an important variable when
      determining selection criteria for the Hybrid implant.

PMID- 19390174
TI  - Results of partial deafness cochlear implantation using various electrode
      designs.
AB  - Nineteen adults and 9 children who received a unilateral cochlear implant between
      2002 and 2007 were included in the study. All subjects were preoperatively
      diagnosed with significant residual hearing in low frequencies, termed as
      'partial deafness', and were implanted according to a 6-step round window
      surgical technique for partial deafness cochlear implantation. Hearing was
      preserved to a great extent in the partial deafness cochlear implantation (PDCI)
      group. After a short period following activation of the cochlear implant, highly
      significant improvement in the recognition of monosyllabic words was observed.
      With a developed round window surgical procedure and limited electrode insertion,
      hearing can be preserved in the majority of patients with partial deafness. PDCI
      is a feasible means of treating individuals who have good low-frequency hearing
      but severe to profound hearing loss in the mid to high frequencies.

PMID- 19390175
TI  - The central vestibular complex in dolphins and humans: functional implications of
      Deiters' nucleus.
AB  - Toothed whales (Odontocetes; e.g., dolphins) are well-known for efficient
      underwater locomotion and for their acrobatic capabilities. Nevertheless, in
      relation to other mammals including the human and with respect to body size,
      their vestibular apparatus is reduced, particularly the semicircular canals.
      Concomitantly, the vestibular nerve and most of the vestibular nuclei are thin
      and small, respectively, in comparison with those in terrestrial mammals. In
      contrast, the lateral (Deiters') vestibular nucleus is comparatively well
      developed in both coastal and pelagic dolphins. In the La Plata dolphin
      (Pontoporia blainvillei) and the Common dolphin (Delphinus delphis), all of the
      vestibular nuclei are present and their topographic relations are similar to
      those in humans. Quantitative analysis, however, revealed that in the dolphin
      most of the nuclei (superior, medial, descending nucleus) are minute both in
      absolute and relative terms. Here, the only exception is the lateral vestibular
      nucleus, which is of comparable size in humans and Pontoporia and decidedly more
      voluminous in Delphinus. While the small size of the majority of the dolphin's
      vestibular nuclei correlates well with miniaturization of the semicircular
      canals, the size of Deiters' nucleus seems to support its relative independence
      from the vestibular system and a close functional relationship with the
      cerebellum. In comparison with findings in humans and other terrestrial mammals,
      both of these aspects seem to be related to the physical conditions of aquatic
      life and locomotion in three dimensions.

PMID- 19390176
TI  - Brain size: a global or induced cost of learning?
AB  - The role of brain size as a cost of learning remains enigmatic; the nature and
      timing of such costs is particularly uncertain. On one hand, comparative studies
      suggest that congenitally large brains promote better learning and memory. In
      that case, brain size exacts a global cost that accrues even if learning does not
      take place; on the other hand, some developmental studies suggest that brains
      grow with experience, indicating a cost that is induced when learning occurs. The
      issue of how costs are incurred is an important one, because global costs are
      expected to constrain the evolution of learning more than would induced costs. We
      tested whether brain size represented a global and/or an induced cost of learning
      in the cabbage white butterfly, Pieris rapae. We assayed the ability of full
      sibling families to learn to locate either green hosts, for which butterflies
      have an innate search bias, or red hosts, which are more difficult to learn to
      locate. Naive butterflies were sacrificed at emergence and congenital brain
      volume estimated as a measure of global costs; experienced butterflies were
      sacrificed after learning and change in brain volume estimated as a measure of
      induced costs. Only for the mushroom body, a brain region involved in learning
      and memory in other insects, was volume at emergence related to learning or host
      finding. Butterfly families that emerged with relatively larger mushroom bodies
      showed a greater tendency to improve their ability to find red hosts across the
      two days of host-search. The volume of most brain regions increased with time in
      a manner suggesting host experience itself was important: first, total number of
      landings during host-search was positively related to mushroom body calyx volume,
      and, second, experience with the red host was positively related to mushroom body
      lobe volume. At the family level, the relative volume of the mushroom body calyx
      and antennal lobes following learning was positively related to overall success
      in finding red hosts. Overall, our results suggest that within species, brain
      size might act as a small global cost of learning, but that environment-specific
      changes in brain size might reduce the overall costs of neural tissue in the
      evolution of learning.

PMID- 19390177
TI  - Digital probabilistic atlas of the border region between the middle and posterior
      cerebral arteries.
AB  - BACKGROUND AND PURPOSE: The diagnosis of external borderzone infarction is made
      when the stroke is located at the border between the arterial territories. Recent
      studies have raised questions regarding the location of this borderzone given the
      variability in the arterial territories. We examined the location of this region
      using a digital approach and its correspondence with the 'traditional' template.
      METHODS: Infarcts resulting from occlusion of the middle cerebral artery (MCA) or
      posterior cerebral artery (PCA) trunk or branches were segmented from T(2)
      weighted MR images and linearly registered into a common stereotaxic coordinate
      space. For MCA infarcts and PCA infarcts, maps of voxels in a rim surrounding the
      infarct were created. The maps of individual rims were averaged to create images
      of the probability of each voxel lying in the MCA and PCA rims. The MCA and PCA
      rims were used to create a digital atlas of the probability of each voxel lying
      concurrently in both rims. RESULTS: The MCA group consisted of 36 patients (16
      males) with a median age of 73 (range 25-87) years. The PCA territory group
      consisted of 30 patients (24 males) with a median age of 61 (range 22-86) years.
      The probability of involvement in the digital atlas was higher in the posterior
      putamen (probability 0.12-0.29) and optic tract (probability 0.13-0.0.20) than in
      the angular gyrus (probability 0.01). CONCLUSION: We have created a digital model
      of the border region between the MCA and PCA territories. This approach may be
      useful for evaluating the likelihood of a stroke mechanism from topography.

PMID- 19390178
TI  - Stroke in the very elderly: hospital care, case fatality and disposition.
AB  - BACKGROUND: The worldwide growing number of older people represents a new
      phenomenon. Considering that the prevalence of stroke increases with age and
      higher life expectancy, the prevalence of stroke will likely rise in the next
      decade. However, limited information is available about the burden of stroke in
      individuals over 90. METHODS: This is a subgroup analysis from a multicenter
      cohort study including individuals admitted with an ischemic stroke to a broad
      range of hospitals across Canada. Patients were identified from the Canadian
      Hospital Morbidity database (HMDB), which is a national database that contains
      patient-level sociodemographic, diagnostic and administrative information.
      Multivariable analysis was performed using logistic regression. Outcomes measures
      include risk-adjusted stroke fatality, ICU admissions, medical complications,
      length of hospital stay and discharge disposition. RESULTS: Among 26,676 patients
      with ischemic stroke admitted to 606 hospitals, 2,015 (7.6%) were aged 90 years
      or older. Risk-adjusted fatality at discharge was 6.3% (age <69), 12.5% (age 70
      79), 22.0% (age 80-89) and 36.1% (age >or=90) (p < 0.001). Patients aged 90 and
      over were more likely admitted on weekends (28.1 vs. 24.6; p < 0.001), and less
      likely to be admitted to the ICU (4.3 vs. 13.0%, p < 0.001) and discharged to
      their pre-stroke residence (39.9% for those over 90 vs. 57.3% for patients
      younger than 90, p < 0.001). In the multivariable analysis, nonagenarians and
      older were 5-8 times more likely to die after adjusting for covariates.
      CONCLUSION: In our study, stroke patients over 90 had higher risk-adjusted
      mortality, longer hospitalization, and were less likely to be discharged to their
      original place of residence. In view of these findings, strategies need to be
      implemented to facilitate equal access to specialized stroke care for the
      elderly.

PMID- 19390179
TI  - C-reactive protein is a determinant of first-ever stroke: prospective nested case
      referent study.
AB  - BACKGROUND AND PURPOSE: C-reactive protein (CRP) is a determinant of stroke, but
      there are no prospective studies on CRP and first ischemic stroke divided into
      etiologic subtypes. Our primary aim was to study CRP as a determinant of ischemic
      stroke, classified according to Trial of ORG 10172 in Acute Stroke Treatment
      (TOAST) criteria, and intracerebral hemorrhage (ICH) in a prospective study. A
      secondary aim was to study the relationship between the 1444C>T polymorphism,
      plasma levels of CRP and stroke. METHODS: The study was a prospective population
      based case-referent study nested within the Northern Sweden Cohorts. We defined
      308 cases of ischemic stroke and 61 ICH. Two controls for each case were defined
      from the same cohort. RESULTS: The OR for the highest (>3 mg/l) versus lowest
      group (<1 mg/l) of CRP was 2.58 (95% CI 1.74-3.84) for ischemic stroke and 1.63
      (95% CI 0.67-3.93) for ICH. In a multivariate model including traditional risk
      factors, CRP remained associated with ischemic stroke (OR 2.06; 95% CI 1.29
      3.29). Small-vessel disease was associated with CRP in the multivariate model (OR
      3.88; 95% CI 1.10-13.7). The CRP 1444 (CC/CT vs. TT) polymorphism was associated
      with plasma levels of CRP but neither with ischemic stroke nor with ICH.
      CONCLUSIONS: This prospective population-based study shows that CRP is
      significantly associated with the risk of having a first ischemic stroke,
      especially for small-vessel disease. No significant associations were found
      between the CRP 1444C>T polymorphism and any stroke subtype.

PMID- 19390180
TI  - Use of Doppler ultrasound to assess femoral artery adaptations in the hemiparetic
      limb in people with stroke.
AB  - BACKGROUND: A reduction in physical activity combined with decreased demand for
      leg oxygen consumption may affect blood flow to the hemiparetic lower extremity
      after stroke. The purpose of this study was to characterize femoral artery
      adaptations that occur in the hemiparetic leg in chronic stroke. A secondary goal
      was to examine intrarater reliability using Doppler ultrasound in people with
      hemiparesis after stroke. METHODS: This descriptive study used a sample of
      convenience at 2 locations (urban medical center and rural university). Eighteen
      individuals (68.4 +/- 3.7 years of age; 15 males) with chronic stroke (time since
      stroke: 5.7 +/- 1.1 years; 12 with right-side hemiparesis) participated in the
      study. Femoral artery blood flow, diameter, velocity and vessel wall thickness in
      the bilateral lower extremities were assessed using Doppler ultrasound.
      Intrarater reliability was determined for femoral artery diameter and blood flow
      velocity. RESULTS: Femoral artery blood flow, arterial diameter and blood flow
      velocity were significantly lower (p < 0.0001) in the hemiparetic limb when
      compared to the less affected limb. Femoral artery vessel wall thickness was
      significantly greater (p = 0.002) in the hemiparetic limb. Doppler ultrasound
      intrarater reliability was strong and significant (intraclass correlation
      coefficient(3,1) >0.94, p < 0.0001) for femoral artery diameter and blood flow
      velocity measurements. CONCLUSION: These data suggest that individuals with
      chronic stroke demonstrate vascular changes in the femoral artery of the
      hemiparetic limb.

PMID- 19390181
TI  - Cerebrovascular ischemic events in HIV-1-infected patients receiving highly
      active antiretroviral therapy: incidence and risk factors.
AB  - BACKGROUND: Stroke risk is increased in AIDS patients, and highly active
      antiretroviral therapy (HAART) may accelerate atherosclerosis, but little is
      known about the incidence and risk factors for ischemic stroke in patients under
      HAART. We have studied the incidence, types of stroke and possible risk factors
      for cerebrovascular ischemic events in a large cohort of HIV-1-infected patients
      treated with HAART. METHODS: We conducted a retrospective review of ischemic
      strokes and transient ischemic attacks occurring in a cohort of HIV-1-infected
      patients treated with HAART from 1996 to 2008. As a control group, consecutive
      unselected patients from the same cohort were included. Patients and controls
      were compared for demographic, clinical and laboratory variables, including
      vascular risk factors, data on HIV infection and duration of HAART. Variables
      with significant differences were included in a backward logistic regression
      model. RESULTS: Twenty-seven cerebrovascular ischemic events occurred in 25
      patients, with an incidence of 189 events (166 strokes) per 100,000
      patients/year. Independent factors associated with cerebrovascular events were:
      history of high alcohol intake (OR 7.13, 95% CI 1.69-30.11; p = 0.007), a
      previous diagnosis of AIDS (OR 6.61, 95% CI 2.03-21.51; p = 0.002) and fewer
      months under HAART (OR 0.97, 95% CI 0.96-0.99; p < 0.001). Six patients (24%) had
      large artery atherosclerosis: they had a similar HAART duration to controls.
      CONCLUSIONS: Stroke incidence is high in patients with HIV-1 infection treated
      with HAART. Duration of HAART exerted a global protective effect for
      cerebrovascular ischemic events, and our results do not support a major role in
      large artery atherosclerosis stroke. High alcohol intake is a major risk factor
      for stroke in these patients.

PMID- 19390182
TI  - Infarction involving the insula and risk of mortality after stroke.
AB  - BACKGROUND: Cerebral infarction involving the insula has been associated with
      decreased survival following stroke. We hypothesized that infarct volume may
      reduce this association. METHODS: The subjects were acute stroke patients who had
      consented to 2-year follow-up after stroke as part of the Michigan Acute Stroke
      Care Overview and Treatment Surveillance System registry. One hundred and eleven
      subjects exhibited areas of acute ischemic infarction on neuroimaging studies, 25
      of whom had infarction involving the insula. Cox proportional hazard ratios (HR)
      were calculated to determine the association between mortality and acute
      infarction involving the insula, infarct volume, and other factors known to
      affect survival after stroke. RESULTS: In unadjusted analysis, subjects with
      insula infarction had a nonsignificant twofold increase in 1-year mortality (HR =
      2.1, 95% CI 0.6-7.0; p = 0.25). When adjusted for infarct volume, however, the HR
      for insula infarction was reduced to the null value (HR = 1.0, 95% CI 0.2-4.1; p
      = 1.00), indicating that the effect of insula infarction was entirely confounded
      by infarct volume. CONCLUSIONS: Insula infarction was associated with a
      nonsignificant twofold increase in mortality after stroke; however, this
      association was completely eliminated after adjusting for infarct volume. Infarct
      volume thus should be considered in future studies of insula infarction and
      mortality.

PMID- 19390183
TI  - Plasticity of circle of Willis: a longitudinal observation of flow patterns in
      the circle of Willis one week after stenting for severe internal carotid artery
      stenosis.
AB  - BACKGROUND AND PURPOSE: The purpose of the present study was to assess whether
      the direction of flow via the circle of Willis (CoW) changed after stenting for
      severe internal carotid artery (ICA) stenosis. METHODS: 65 patients (38 men, mean
      age 63.2 +/- 8.4 years, range 44-82) with a symptomatic ICA occlusion were
      investigated. Magnetic resonance angiography was performed prior to and 1 week
      after carotid artery stenting (CAS). The pattern in the CoW was assessed.
      RESULTS: One third of the subjects (35.38%) had a significantly altered flow
      pattern in the CoW after unilateral CAS, including blocked ipsilateral A1 segment
      collateral (n = 4), blocked contralateral A1 segment collateral (n = 5), blocked
      ipsilateral posterior communicating artery (PCoA) segment collateral (n = 4),
      blocked ipsilateral A1 segment and P1 segment collateral (n = 1), opening of
      ipsilateral A1 segment collateral (n = 5), opening of ipsilateral PCoA segment
      collateral (n = 3) and opening of ipsilateral P1 segment collateral (n = 1).
      CONCLUSIONS: CoW segmental hypoplasia is not a static feature. Willisian
      collateralization with recruitment of the CoW segment (A1, P1 and PCoA) may be
      blocked after CAS. CAS also leads to the opening of new willisian
      collateralization, either for relief of reperfusion pressure or for other
      hypoperfused areas.

PMID- 19390184
TI  - Transcranial Doppler ultrasound in the acute phase of aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND: Angiographic studies suggest that acute vasospasm within 48 h of
      aneurysmal subarachnoid hemorrhage (SAH) predicts symptomatic vasospasm. However,
      the value of transcranial Doppler within 48 h of SAH is unknown. METHODS: We
      analyzed 199 patients who had at least 1 middle cerebral artery (MCA)
      transcranial Doppler examination within 48 h of SAH onset. Abnormal MCA mean
      blood flow velocity (mBFV) was defined as >90 cm/s. Delayed cerebral ischemia
      (DCI) was defined as clinical deterioration or radiological evidence of
      infarction due to vasospasm. RESULTS: Seventy-six patients (38%) had an elevation
      of MCA mBFV >90 cm/s within 48 h of SAH onset. The predictors of elevated mBFV
      included younger age (OR = 0.97 per year of age, p = 0.002), admission
      angiographic vasospasm (OR = 5.4, p = 0.009) and elevated white blood cell count
      (OR = 1.1 per 1,000 white blood cells, p = 0.003). Patients with elevated mBFV
      were more likely to experience a 10 cm/s fall in velocity at the first follow-up
      than those with normal baseline velocities (24 vs. 10%, p < 0.01), suggestive of
      resolving spasm. DCI developed in 19% of the patients. An elevated admission mBFV
      >90 cm/s during the first 48 h (adjusted OR = 2.7, p = 0.007) and a poor clinical
      grade (Hunt-Hess score 4 or 5, OR = 3.2, p = 0.002) were associated with a
      significant increase in the risk of DCI. CONCLUSION: Early elevations of mBFV
      correlate with acute angiographic vasospasm and are associated with a
      significantly increased risk of DCI. Transcranial Doppler ultrasound may be an
      early useful tool to identify patients at higher risk to develop DCI after SAH.

PMID- 19390185
TI  - Influence of cyclooxygenase-1 genotype on ex vivo aspirin response in patients at
      risk for stroke.
AB  - BACKGROUND: We sought to determine whether cyclooxygenase-1 (PTGS1) genotype is
      associated with the ability of aspirin to inhibit platelet aggregation in
      patients at risk for stroke. METHODS: Blood and urine samples were collected from
      60 subjects, including 28 African Americans, who were taking aspirin for primary
      or secondary stroke prevention. Samples were analyzed for the PTGS1 A-707G, PTGS1
      P17L, and glycoprotein IIIa (ITGB3)P1(A1/A2) genotypes, ex-vivo platelet
      aggregation, serum cholesterol, plasma salicylate levels, and urinary 11
      dehydrothromboxane B(2) (11-dhTxB(2)) concentrations. The association between
      PTGS1 A-707G and P17L genotypes and aspirin response, as assessed by ex vivo
      studies and 11-dhTxB(2) concentrations, was evaluated by statistical testing and
      nonlinear mapping. RESULTS: Salicylate concentrations, ITGB3 genotype
      distribution and 11-dhTxB(2) concentrations were similar among PTGS1 genotype
      groups. More subjects with the PTGS1 17PP versus PL genotype had incomplete ex
      vivo inhibition of platelet aggregation by aspirin (57 vs. 20%; p = 0.04). Fifty
      nine percent of subjects homozygous for both the PTGS -707A and 17P alleles, but
      none with both the PTGS1 -707G and 17L alleles had incomplete inhibition with
      aspirin; p = 0.04. Similarly, nonlinear mapping showed a direct relationship
      between the PTGS1 17P allele and decreased aspirin response. When analyzed
      separately by ethnicity, the association with the P17L genotype and aspirin
      response persisted in African Americans, but not Caucasians. CONCLUSIONS: Our
      data suggest that the PTGS1 P17L genotype contributes to response to aspirin as
      assessed by ex-vivo platelet aggregation. Our data further suggest that the
      association between PTGS1 genotype and aspirin response might vary by ethnicity.

PMID- 19390186
TI  - Transient ischemic attack patients with fluctuations are at highest risk for
      early stroke.
AB  - BACKGROUND: The management and risk of early stroke are unclear in patients with
      fluctuating neurological symptoms. We aimed to evaluate the clinical course of
      these patients presenting within 24 h after onset of acute cerebral ischemia
      symptoms. METHODS: All patients with transient ischemic signs/symptoms
      consecutively admitted to our Emergency Stroke Unit were recruited. Patients were
      neurologically examined and underwent prompt CCT plus MRI imaging for
      visualization of early signs of ischemia. RESULTS: Among 122 patients, 84 (69%)
      had single symptoms, 33 (27%) showed rapidly relapsing and remitting symptoms -
      in 5 cases (4%) symptom duration could not reliably be assessed. 11/122 (9%)
      suffered a stroke during hospitalization. ABCD(2) scores did not predict early
      strokes: 2/11 (18.2%) were in the 'lower risk', 7/11 (63.6%) in the 'moderate
      risk' and only 2/11 (18.2%) in the 'high risk' group (p = 0.103). 3/11 patients
      (27.3%) revealed lesions in neuroimaging, but surprisingly 8/11 (72.7%, p =
      0.132) did not. However, patients with fluctuations in neurological status were
      significantly more likely to suffer a stroke: 9/122 versus 2/122 with stable
      symptoms (p < 0.05). Patients with small vessel disease were common in all (53/
      122; 43.4%) and within those who suffered an early stroke (6/11; 54.5%).
      CONCLUSIONS: Patients with unstable transient ischemic attacks immediately after
      onset of clinical symptoms are at high risk for subsequent stroke - they may
      benefit from Stroke Unit management and potential early thrombolysis once they
      develop strokes.

PMID- 19390187
TI  - Preradiation chemotherapy with ACNU-CDDP in patients with newly diagnosed
      glioblastoma: a retrospective analysis.
AB  - OBJECTIVE: We evaluated the benefit of preradiation chemotherapy with ACNU
      (nimustine) and CDDP (cisplatin) in patients with newly diagnosed glioblastoma by
      retrospective analysis. METHODS: A total of 151 patients were newly confirmed to
      have glioblastoma between January 2000 and December 2004. All patients underwent
      surgical resection: 38 (25.2%) patients underwent complete resection, 73 (48.3%)
      underwent incomplete resection and 40 (26.5%) underwent biopsy. Preradiation
      chemotherapy using ACNU-CDDP was administered as an initial adjuvant therapy for
      87 (57.6%) patients (ACNU-CDDP group), radiation therapy was performed in 31
      (20.5%) patients (RT group) and the remaining 33 (21.9%) patients were treated
      with other regimens or refused to undergo further treatment. RESULTS: The median
      survival time was 13 months (95% CI 11.29-14.71), and the overall survival rate
      was 54.0% at 1 year and 21.3% at 2 years. The differences in median survival time
      between the complete resection group and biopsy group and between the ACNU-CDDP
      group and RT group were significant (15.0 vs. 10 months, p = 0.028, and 16.0 vs.
      12.0 months, p = 0.036, respectively) in the univariate analyses. Even in the
      multivariate analysis, preradiation chemotherapy using ACNU-CDDP had a
      significant effect on survival prolongation (HR = 0.628, p = 0.042). The usage of
      temozolomide for adjuvant or salvage therapy also had an independent and
      significantly positive effect on survival (HR = 0.511, p = 0.006). Grade 3 and 4
      hematologic toxicities occurred in 28 (32.1%) patients in the ACNU-CDDP group,
      but there were no treatment-related deaths. CONCLUSION: Preradiation chemotherapy
      with ACNU-CDDP as an initial therapy for patients with newly diagnosed
      glioblastoma is feasible and should be assessed in a randomized phase III study.

PMID- 19390188
TI  - Cisplatin plus gemcitabine chemotherapy in taxane/anthracycline-resistant
      metastatic breast cancer.
AB  - BACKGROUND: The most commonly used chemotherapeutic regimens in the treatment of
      metastatic breast cancer (MBC) include anthracyclines and taxanes. In our study,
      we investigated the efficacy and tolerability of cisplatin plus gemcitabine
      combination chemotherapy regimen in patients with MBC, who exhibited disease
      progression after anthracycline- and taxane-based chemotherapy. METHODS: Thirty
      three patients with taxane/anthracycline-resistant MBC have been treated with
      gemcitabine 1,000 mg/m(2) intravenously and cisplatin 30 mg/m(2) intravenously on
      days 1 and 8 of a 3-week treatment cycle. RESULTS: Thirty-one patients were
      assessable for response. One of the 31 patients (3.2%) showed complete response,
      while 7 patients (22.6%) showed partial response; the objective response rate was
      25.8%. Stable and progressive disease was observed in 6 (19.4%) and 17 patients
      (54.8%), respectively. The median time to progression was 4 months (95% CI 2.15
      5.85). The median survival time of all patients was 9.5 months (95% CI 7.86
      11.14). CONCLUSION: Gemcitabine and cisplatin combination therapy is moderately
      active and safe in patients with MBC previously treated with anthracycline and
      taxanes.

PMID- 19390189
TI  - Comparison of in vitro activities of tigecycline with other antimicrobial agents
      against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella
      catarrhalis in two university hospitals in Istanbul, Turkey.
AB  - BACKGROUND: We compared the in vitro activities of tigecycline with those of
      other agents against 97 Streptococcus pneumoniae, 140 Haemophilus influenzae and
      54 Moraxella catarrhalis strains isolated in two large university hospitals in
      Istanbul. METHODS: For analysis, the agar dilution method was used. RESULTS: For
      S. pneumoniae isolates, 32% were not susceptible to penicillin (28.9%
      intermediate and 3.1% resistant). Cefotaxime, telithromycin, moxifloxacin and
      linezolid were fully active. Tigecycline had a 90% minimum inhibitory
      concentration (MIC(90)) of 0.12 microg/ml. For H. influenzae, 8.57% were not
      susceptible to ampicillin, among which 8 possessed beta-lactamase (5.7%). Four
      (2.87%) H. influenzae isolates with beta-lactamase-negative and ampicillin
      resistant phenotype were found. All isolates were susceptible to ceftriaxone,
      azithromycin, ciprofloxacin, levofloxacin and moxifloxacin. MIC(90) for
      tigecycline was 0.5 microg/ml. Of 54 M. catarrhalis isolates, 88.9% possessed
      beta-lactamase. Tigecycline and fluoroquinolones were highly active (MIC(90) < or
      =0.12 microg/ml). CONCLUSIONS: Linezolid, telithromycin, newer fluoroquinolones
      and tigecycline all have excellent in vitro activities against the 3 respiratory
      pathogens.

PMID- 19390190
TI  - Individual variations in protective effects of experimentally formed salivary
      pellicles.
AB  - Salivary proteins protect teeth against acid-induced softening and
      demineralization by forming a pellicle. However, little is known about
      individual, gender and ethnic variations in this effect. Therefore, we aimed to
      determine differences in protective effects of experimentally formed pellicles
      from 10 healthy young Scandinavians (3 women and 7 men) and 10 healthy young non
      Scandinavians (4 women and 6 men) including Arabic, Persian, Pakistan, Indian,
      and Chinese subjects. Bovine enamel blocks, which were precoated with parotid and
      submandibular salivary proteins for 12 h, were exposed to an acidic solution with
      surface microhardness (SMH) determinations before and after. No change in SMH
      equalled 100% protection, whereas SMH corresponding to no protein coating
      equalled 0%. The results showed that experimentally formed pellicles from non
      Scandinavians protected enamel better than pellicles from Scandinavians (p <
      0.001). Within groups protective effects of pellicles formed from parotid and
      submandibular saliva were equal and subjects with high protection from parotid
      saliva pellicles also had high protection from submandibular saliva pellicles (r
      = 0.78; p < 0.001). Within groups considerable differences were obtained among
      individuals ranging from 25 to 51% protection. However, SDS-PAGE and HPLC did not
      reveal any systematic relation between saliva protein composition and protective
      effects, although slightly more of the SN-isoform of S-type cystatin was found in
      pooled parotid saliva from those non-Scandinavian subjects showing highest
      protection. We conclude that individual variations in experimental pellicle
      protection against erosive challenges exist and that such variations appear not
      to be due to differences in a single protein component.

PMID- 19390191
TI  - Human milk compounds inhibiting adhesion of mutans streptococci to host ligand
      coated hydroxyapatite in vitro.
AB  - Acquisition of mutans streptococci at an early age is a risk factor for later
      caries development. Following our recent finding that human milk may inhibit
      adhesion of Streptococcus mutans the aim of the present study was to identify
      compounds in human milk preventing adhesion of mutans streptococci to saliva- or
      gp340-coated hydroxyapatite (s-HA and gp340-HA) using an in vitro model system.
      Superdex 200 fractions of human milk and purified proteins were screened for
      binding inhibition of the S. mutans strain Ingbritt. Avid inhibition was seen to
      both s-HA and gp340-HA for caseins, lactoferrin, IgA and IgG, and moderate
      inhibition for alpha-lactalbumin and bile salt-stimulated lipase, whereas albumin
      and lysozyme had no effect. The inhibitory epitope in beta-casein was delineated
      to its C-terminal LLNQELLNPTHQIYPVTQPLAPVHNPISV stretch by use of synthetic
      peptides. Similarly, a peptide (SCKFDEYFSQSCA) corresponding to the human
      lactoferrin stretch that is highly homologous to the previously shown inhibitory
      stretch of bovine lactoferrin was found to inhibit S. mutans Ingbritt binding.
      Inhibition by human milk, IgA, and the inhibitory beta-casein peptide was
      universal among 4 strains of S. mutans (Ingbritt, NG8, LT11, JBP) and 2 strains
      of S. sobrinus (6715 and OMZ176). IgG inhibited 4, alpha-lactalbumin 3 and
      lactoferrin 2 of these 6 strains. It was also confirmed that none of the milk
      components coated on HA mediated S. mutans Ingbritt adhesion, which was
      consistent with the finding that no milk protein was recognized on Western blots
      by gp340/DMBT1 monoclonal antibodies.

PMID- 19390192
TI  - Leukopenia due to parvovirus B19 in a Crohn's disease patient using azathioprine.
AB  - Thiopurines such as azathioprine (AZA) and 6-mercaptopurine are frequently used
      for the treatment of inflammatory bowel diseases. Patients with low or absent
      thiopurine S-methyltransferase (TPMT) activity, resulting in high 6-thioguanine
      nucleotide levels, have an increased risk of developing leukopenia.
      Alternatively, certain viral infections could induce leukopenia. We present the
      case of an adult Crohn's disease patient with a parvovirus B19 infection and
      leukopenia during long-term AZA therapy. The uncomplicated long-term use of
      adequately-dosed AZA and stable non-toxic metabolite levels could not acknowledge
      TPMT deficiency as a primary cause of the leukopenia. parvovirus B19 was assumed
      to induce the leukopenia by restraining myeloid proliferation. In addition, AZA
      probably potentiated susceptibility to this viral infection and may have
      inhibited adequate immunological defense. Leukopenia during thiopurine therapy
      not explained by TPMT deficiency could be induced by parvovirus B19 infection and
      compels temporal but not permanent cessation of thiopurine therapy.

PMID- 19390193
TI  - Simultaneous occurrence of inflammatory bowel disease and myelodysplastic
      syndrome due to chromosomal abnormalities in bone marrow cells.
AB  - BACKGROUND/AIMS: Although chromosomal abnormalities in bone marrow (BM) cells,
      such as trisomy 8, are risk factors for the development of inflammatory bowel
      diseases (IBD) as well as myelodysplastic syndrome (MDS), the mechanisms of how
      these cytogenetic abnormalities cause intestinal inflammation are poorly
      understood. METHODS AND RESULTS: A 55-year-old man with a 3-month history of
      watery diarrhea, fever and abdominal pain was admitted. Blood examinations
      revealed pancytopenia. Pathological analysis and endoscopic images of the entire
      colon led to the diagnosis of IBD of unclassified type. BM examination showed
      that the pancytopenia was due to MDS and that his BM cells had dual chromosomal
      abnormalities: 47, XY, +1, der(1;7)(q10;p10), +8. Immunological studies using
      peripheral blood monocytes from this patient revealed that the dual chromosomal
      abnormalities of BM cells led to the development of colitogenic monocytes
      producing a large amount of pro-inflammatory cytokines and showing resistance to
      apoptosis upon stimulation with microbial antigens. CONCLUSION: An abnormal
      karyotype of BM cells is not only responsible for the development of MDS, but
      also for IBD in this case.

PMID- 19390194
TI  - Immunoglobulin G4-associated cholangitis: one variant of immunoglobulin G4
      related systemic disease.
AB  - IgG4-associated cholangitis (IAC) is a recently defined disease entity which
      shares a number of clinical, biochemical, and radiological features with primary
      sclerosing cholangitis (PSC). In contrast to PSC, IAC responds to
      immunosuppressive treatment, is not associated with inflammatory bowel disease,
      and mainly affects elderly men above the age of 60 years. Today, IAC is regarded
      as one variant of IgG4-related systemic disease (ISD) of which autoimmune
      pancreatitis (AIP) is the best studied organ manifestation. The diagnosis of IAC
      is based on biochemical, radiological and histologic features, among which
      elevated serum levels of IgG4, extra- and intrahepatic biliary strictures as
      visualized by cholangiography, multifocal IgG4-rich lymphoplasmacytic sclerosing
      infiltrations in liver and bile duct tissue, and association with AIP are of key
      importance. This review aims at summarizing clinical features, diagnostic
      criteria, therapeutic strategies and most recent insights in the pathophysiology
      of IAC and other organ manifestations of ISD.

PMID- 19390195
TI  - Relation of gallbladder motility to viscosity and composition of gallbladder bile
      in patients with cholesterol gallstones.
AB  - BACKGROUND/AIMS: Increased viscosity and supersaturation of cholesterol in
      gallbladder bile, as well as an impaired motility of the gallbladder, are
      considered to be important factors in the pathogenesis of cholesterol gallstones.
      However, the relation of these parameters has not yet been determined. MATERIAL
      AND METHODS: Bile viscosity (mPa s) was measured by rotation viscosimetry and the
      composition of gallbladder bile was determined using standard methodology.
      Gallbladder motility was calculated as ejection fraction in percent of total
      volume 45 min after a test meal using ultrasonography in patients with gallstones
      prior to elective cholecystectomy. RESULTS: The study included 35 patients with
      cholesterol gallstones. Viscosity of gallbladder bile ranged between 0.9 and 12.5
      mPa s (median 2.2 mPa s) and an ejection fraction of the gallbladder of 55.4 +/-
      18.3% (mean +/- SD) was determined. No significant correlation (r = 0.19, p <
      0.2) between the 2 parameters could be calculated. Analysis of the composition of
      gallbladder bile revealed a positive correlation of all components to biliary
      viscosity but not to the motility of the gallbladder, with the exceptions of a
      negative correlation (r = 0.39, p < 0.02) between mucin concentration and the
      ejection fraction at 45 min after the test meal. CONCLUSIONS: The motility of the
      gallbladder appears to be unrelated to the viscosity of gallbladder bile or
      gallbladder bile composition. The negative correlation between the ejection
      fraction of the gallbladder and mucin concentration of gallbladder bile suggests
      that chronic inflammation of the gallbladder wall is associated with both an
      impaired motility of the gallbladder and increased mucin release into gallbladder
      bile.

PMID- 19390196
TI  - Ultrasonography and clinical observation in women with suspected acute
      appendicitis: a prospective cohort study.
AB  - BACKGROUNDS/AIMS: It was the aim of this study to evaluate the role of
      ultrasonography (US) and clinical observation in non-pregnant women of
      reproductive age with suspected appendicitis. METHODS: In a prospective cohort
      study, US was performed in 234 women with suspected appendicitis. Based on US
      findings and clinical assessment, 3 patient categories were established. Group A:
      unequivocal signs--laparoscopy (regardless of US results); group B:
      equivocalsigns--positive US--laparoscopy; group C: equivocal signs--negative US-
      observation. US results were compared with surgery, observation and follow-up as
      the reference standard. RESULTS: The percentages of macroscopically infected
      appendices at laparoscopy in groups A, B and C were 76, 55 and 5%, respectively.
      Group A: US was false negative in 27 of 128 women (21%) and false positive in 12
      of 40 women (30%). Group B plus C: US was false negative in 3 of 9 women (33%)
      and false positive in 5 of 57 women (9%). Forty-six of 55 patients (84%)
      completed observation. CONCLUSION: Because of a high false-negative rate, US as a
      sole imaging tool is of limited value both in women with unequivocal and
      equivocal signs of appendicitis. Observation is safe in women with equivocal
      signs of appendicitis.

PMID- 19390197
TI  - Effects of centralization of colorectal surgery on the outcome of patients with
      distal sigmoid colonic cancer.
AB  - BACKGROUND: In 1996, all colorectal surgery in the county of Vastmanland, Sweden,
      was centralized to the central District Hospital in Vasteras. A Colorectal Unit
      was established and modern surgical procedures were introduced. The aim of this
      study was to analyze the outcome for patients treated surgically for distal
      sigmoid colonic cancer before and after the centralization. METHODS: Hospital
      records of all patients with distal sigmoid colonic cancer, treated between 1991
      1995, group 1 (n = 64), and 1996-2000, group 2 (n = 82), were studied
      retrospectively. RESULTS: In group 2, there were fewer reoperations (n = 0) than
      in group 1 (n = 6; p = 0.005) and the postoperative mortality was lower; one in
      group 2 compared with five in group 1 (p = 0.047). The amount of lymph nodes
      examined were higher and the length of distal surgical margin longer in group 2.
      Curatively treated patients in group 2 had better overall survival compared to
      group 1 (RR 0.56; 95% CI 0.34-0.93). CONCLUSION: Centralization of colorectal
      surgery resulted in an improvement of pathologic specimens and a decrease in
      postoperative reoperations and mortality in patients treated surgically for
      distal sigmoid colonic cancer. Moreover, the overall survival of curatively
      treated patients was improved.

PMID- 19390198
TI  - Patterns of alcohol consumption and acute myocardial infarction: a case-crossover
      analysis.
AB  - BACKGROUND: Alcohol consumption has been causally related to the incidence of
      coronary heart disease, but the role of alcohol before the event has not been
      explored in depth. This study tested the hypothesis that heavy drinking (binge
      drinking) increases the risk of subsequent acute myocardial infarctions (AMI),
      whereas light to moderate drinking occasions decrease the risk. METHODS: Case
      crossover design of 250 incident AMI cases in Switzerland, with main hypotheses
      tested by conditional logistic regression. RESULTS: Alcohol consumption 12 h
      before the event significantly increased the risk of AMI (OR 3.1; 95% CI 1.4
      6.9). Separately, the effects of moderate and binge drinking before the event on
      AMI were of similar size but did not reach significance. In addition, AMI
      patients showed more binge drinking than comparable control subjects from the
      Swiss general population. CONCLUSIONS: We found no evidence that alcohol
      consumption before the event had protective effects on AMI. Instead, alcohol
      consumption increased the risk.

PMID- 19390199
TI  - Ligasure vessel sealing system versus harmonic scalpel for sutureless
      nonanatomical pulmonary resections in a rabbit model. Which one is safer?
AB  - BACKGROUND: The safety and efficacy of the ligasure vessel sealing system (LVSS)
      and harmonic scalpel (HS) in sutureless nonanatomical lung resections were
      evaluated. METHODS: On twenty adult rabbit lungs, 1 x 1 cm wedge resections were
      performed under one-lung ventilation with both LVSS and HS. The air tightness and
      tissue damage caused by these different techniques were measured and compared.
      RESULTS: No statistically significant differences were found when the air
      tightness for both devices was compared after resection (p = 0.37). Tissue damage
      was obtained for LVSS, and the difference was statistically significant (p <
      0.001). discussion: LVSS and HS can both be used for peripheral lung resections
      without any need of further intervention for securing the air tightness. LVSS was
      found safer by means of tissue damage when compared with HS in this experimental
      study.

PMID- 19390200
TI  - Group structure and physical characteristics of Simakobu monkeys (Simias
      concolor) on the Mentawai Island of Siberut, Indonesia.
AB  - We present data on group structure and physical characteristics from free-ranging
      Simias concolor. Mean group size (n = 3) was 8.7 +/- 1.1 individuals with an
      average adult male:female sex ratio of 1:3. All individuals were sexed and
      allocated into three categories (infants, juveniles plus subadults and adults) on
      the basis of their physical development. Within age categories, head-body lengths
      ranged from 19.6 to 25, 34 to 44 and 42 to 53 cm. Corresponding body weights
      ranged from 0.5 to 0.9, 2.35 to 4.4 and 5.2 to 7.85 kg, respectively; on average
      adult males were 13% larger and 23% heavier than adult females. Results indicate
      that for S. concolor living in undisturbed habitat (i) group sizes are larger
      than previously reported and (ii) polygyny is the most likely mating system. Both
      results support an earlier proposal that group size and social organization in
      Simakobu monkey are related to the degree of habitat disturbance.

PMID- 19390201
TI  - Serum amyloid a protein and C-reactive protein in normal pregnancy and
      preeclampsia.
AB  - AIMS: To study plasma levels of serum amyloid A protein and C-reactive protein in
      pregnant women with and without preeclampsia and non-pregnant women. Plasma
      levels of haptoglobin, orosomucoid and ceruloplasmin were also analyzed. METHODS:
      The study included 295 women with uncomplicated pregnancies, 57 women diagnosed
      with preeclampsia, and 58 healthy non-pregnant women. Plasma concentrations of
      acute phase proteins were analyzed by particle-enhanced immunoassays. Non
      parametric Kruskal-Wallis and Mann-Whitney U tests were used to test differences
      between the groups. RESULTS: Plasma levels of C-reactive protein and
      ceruloplasmin were increased in pregnant women with and without preeclampsia
      compared to non-pregnant women. Plasma levels of serum amyloid A protein and C
      reactive protein were not elevated in women with preeclampsia compared to women
      with normal pregnancy. CONCLUSION: The description of preeclampsia as a systemic
      inflammatory state was not reflected in the plasma levels of serum amyloid A
      protein and C-reactive protein.

PMID- 19390202
TI  - Fifty years of research in Balkan endemic nephropathy: where are we now?
AB  - Despite broad investigations into the possible role of genetic factors,
      environmental agents and immune mechanisms, the etiology of Balkan endemic
      nephropathy (BEN) is only partially understood. An increased incidence of upper
      urothelial cancer in patients with BEN and in populations from endemic
      settlements has been demonstrated. Genetic studies have landed support for
      genetic predisposition to BEN. The similarity of the morphological and clinical
      pattern of BEN and Chinese herbs nephropathy has raised the possibility of a
      common etiologic agent, aristolochic acid (AA), described in 1969 by Ivic and
      confirmed by a recent study of AA-DNA adducts. Ochratoxin A (OTA) is studied
      extensively as the etiologic agent of BEN. Weathering of low-rank coals nearby
      the endemic villages produces water-soluble polycyclic aromatic hydrocarbons and
      aromatic amines, similar to metabolic products of acetaminophen, which has a
      causal relationship with analgesic nephropathy. AA is confirmed as the etiologic
      agent of BEN; however, it may not be the sole risk factor. More research is
      needed on the patterns of BEN over time and between different endemic places.
      Therefore, it is important to test etiological hypotheses in different endemic
      foci, preferably as a multicentric research. An international approach to solving
      the etiology of BEN is needed in the coming years. The geographic correlation and
      presence of AA-DNA adducts in both BEN and associated urothelial cancer support
      the hypothesis that these diseases share a common etiology.

PMID- 19390203
TI  - HLA-DR, -DQB typing of steroid-sensitive idiopathic nephrotic syndrome children
      in Taiwan.
AB  - BACKGROUND: The association between human leukocyte antigens (HLA) and idiopathic
      nephrotic syndrome (INS) in children has been discussed in various studies.
      METHODS: In this study, 59 Chinese children with steroid-sensitive nephritic
      syndrome (SSNS) in Taiwan were enrolled, and 33 patients underwent renal biopsy.
      RESULTS: The frequency of HLA-DR11 was found to be significantly higher and HLA
      DR14 was lower in SSNS patients as compared with the healthy control group. In
      frequent relapsers, HLA-DR4 was more frequent, while HLA-DQB1*0602 was less
      frequent, as compared with infrequent relapsers. However, there was no
      significant difference between steroid-dependent and non-steroid-dependent
      patients. In patients who showed a response to levamisole, the HLA-DR9 and 
      DQB1*0303 alleles were more frequent, while HLA-DR13 was less frequent. In a
      comparison of HLA in different INS pathologies, HLA-DQB1*0401 was significantly
      frequent in IgM nephropathy. Even though we compared each group with the control
      group separately, the HLA distributions of both groups still differed from each
      other. Our data suggest that the immunogenic characteristics of children with
      SSNS in Taiwan are different from those of other populations. The common motif
      between different HLA alleles and the three-dimensional crystal structures may
      offer an explanation for the varying results from different populations.
      CONCLUSION: According to HLA typing, the results support the hypothesis that IgM
      nephropathy is a different entity from minimal change nephrotic syndrome.

PMID- 19390204
TI  - Acute and transient podocyte loss and proteinuria in preeclampsia.
AB  - Glomerular podocytes are known to regulate proteinuria and podocyturia correlated
      with proteinuria. Podocyturia, the urinary excretion of viable podocytes
      (glomerular epithelial cells), has been associated with proteinuria in
      preeclampsia. This study is the first to investigate the time course alterations
      of podocyturia in patients with preeclampsia (11 cases) and normotensive pregnant
      women (45 cases). Urinalysis was performed at 35 weeks of gestation, 4 days after
      delivery, and 1 month after delivery. In patients with preeclampsia, podocyturia
      was evident at 35 weeks of gestation and 4 days after delivery, while proteinuria
      had already decreased at 4 days after delivery. At 1 month after delivery, almost
      no patients exhibited podocyturia. In control cases, proteinuria was not
      significant throughout the study period. However, 9 of the 45 controls exhibited
      transient and mild podocyturia at 4 days after delivery without proteinuria or
      hypertension. Statistics indicated a correlation between urinary podocyte number
      and blood pressure, but not with proteinuria. In conclusion, podocyturia in
      preeclampsia is transient and almost synchronous with heavy proteinuria. The
      results suggest that acute podocyte loss implicates podocyturia as the possible
      mechanism of proteinuria in women with preeclampsia.

PMID- 19390206
TI  - Kidney disease is a negative predictor of 30-day survival after acute ischaemic
      stroke.
AB  - BACKGROUND/AIMS: Impaired renal function is a strong risk factor for
      cardiovascular diseases and worsens a patient's prognosis. Renal dysfunction
      predicts mortality after acute stroke in the long term. On the other hand, in
      hospital mortality after acute stroke is strongly associated with disorders of
      consciousness at the onset of stroke, severity of stroke, body temperature, blood
      sugar and some other comorbidities. The aim of the study was to analyze the
      possible role of renal dysfunction and/or signs of renal disease (proteinuria) on
      30-day mortality after acute ischaemic stroke (AIS) based on the hospital medical
      records of one county. METHODS: Medical records of 312 consecutive patients
      admitted to Ostroleka County Hospital (Department of Neurology) between March
      2000 and October 2002 for AIS were retrieved retrospectively to determine factors
      influencing 30-day survival. None of patients received thrombolytic therapy.
      RESULTS: Among the patients analyzed, 74 (23.7%) died during the 30-day period.
      In a simple Cox proportional hazards regression model, negative predictive
      factors were: older age, higher pulse rate, lower estimated glomerular filtration
      rate (eGFR), proteinuria, elevated plasma glucose level, diabetes mellitus,
      atrial fibrillation and chronic heart failure. In a multivariate analysis,
      independent negative predictors of 30-day morbidity were: age hazard ratio (HR)
      1.05 (95% CI 1.02-1.08), eGFR <60 ml/min HR 1.75 (95% CI 1.21-2.19), dipstick
      proteinuria HR 2.28 (95% CI 1.74-2.82) and plasma glucose level >100 mg/dl HR
      2.96 (95% CI 2.22-3.70). CONCLUSION: The results of this study identify decreased
      eGFR and presence of dipstick proteinuria as a strong negative predictor of 30
      day survival after AIS in patients not treated with thrombolytic agents.

PMID- 19390205
TI  - Impact of obesity on IgA nephropathy: comparative ultrastructural study between
      obese and non-obese patients.
AB  - BACKGROUND: The pathological role of obesity in the progression of glomerular
      lesions has rarely been studied in primary glomerular diseases. The purpose of
      this study is to investigate the influence of non-diabetic obesity on
      clinicopathological findings in IgA nephropathy. METHODS: 74 patients with biopsy
      proven IgA nephropathy were retrospectively divided into two groups according to
      the criteria for obesity in Japan: non-obese group (group N: n = 50) with BMI <25
      kg/m(2), and obese group (group O: n = 24) with BMI > or =25 kg/m(2). Clinical
      and pathological data at the time of renal biopsy were analyzed. Moreover, the
      outcome of proteinuria in patients treated with angiotensin-converting enzyme
      inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) was evaluated in
      different groups after a 1-year follow-up. RESULTS: Urinary protein excretion was
      significantly greater in the obese group compared to normal-weight patients (p <
      0.05). There was no significant difference in the prevalence of hypertension and
      hyperlipidemia. By light microscopy, the obese group showed significantly larger
      glomerular size (p < 0.0001). On the other hand, the severity of mesangial matrix
      expansion and crescent formation revealed no difference between the two groups.
      By electron microscopy, glomerular basement membrane (GBM) thickness was
      significantly increased in obese patients (p < 0.001). Among 61 patients who were
      followed up for 1 year in our institute, 15 patients were treated with ACE-I or
      ARB without steroids. ACE-I or ARB treatment without steroids tended to reduce
      proteinuria in the obese patients, but this change did not achieve statistical
      significance. CONCLUSIONS: In IgA nephropathy, obesity induces not only
      glomerular enlargement but also ultrastructural modification of GBM, which would
      contribute to increase proteinuria.

PMID- 19390207
TI  - Alcohol consumption and kidney function in IgA glomerulonephritis.
AB  - BACKGROUND: IgA glomerulonephritis (IgAGN) is a kidney disease with variable
      prognosis. Several known risk factors exist for a more progressive course. Some
      population studies indicate that moderate alcohol consumption might protect
      kidney function, but the relationship between alcohol intake and IgAGN has not
      previously been examined. METHODS: We examined 158 (95 men) IgAGN patients (37
      abstainers, 80 light drinkers, 25 moderate drinkers and 16 heavy drinkers) in a
      cross-sectional study. The definition of alcohol consumption was based on
      interviews on the amounts of alcohol intake combined with measurements of serum
      carbohydrate-deficient transferrin, a specific biomarker of alcohol abuse.
      Longitudinal data on renal function were available from 117 patients (76 men) in
      whom an analysis with respect to progression was also performed. RESULTS:
      Moderate drinkers showed the best kidney function. When adjusted by hypertension
      and 24-hour protein excretion, moderate alcohol consumption in a cross-sectional
      multivariate analysis, and both light and moderate alcohol consumption in a
      longitudinal multivariate analysis were significant factors of better kidney
      function. When the study population was divided by gender, the best kidney
      function was among light drinkers in women and among moderate drinkers in men.
      CONCLUSIONS: Moderate alcohol consumption might have a favorable impact on the
      progression of IgAGN. Light alcohol consumption in women and moderate consumption
      in men are associated with improved indices of the glomerular filtration
      estimates in patients with IgAGN.

PMID- 19390208
TI  - Counselling prior to blood-borne virus screening in haemodialysis patients: a
      survey of patient experience and opinion.
AB  - BACKGROUND: Patients with end-stage renal disease receiving renal replacement
      therapy are at higher risk of infection with hepatitis B, C and HIV viruses as
      compared to the general population. Early screening, education and vaccination
      potentially reduce the risk of acquiring these viruses and therefore future
      morbidity and mortality. We have sought to establish the opinions, perceptions
      and understanding of patients regarding the routine testing for blood-borne
      viruses (BBV) to help improve testing strategies. METHODS: An anonymised survey
      was conducted in all local dialysis patients that asked their understanding,
      knowledge and opinions on BBV screening and counselling. RESULTS: 55.3% (167/302)
      of all local dialysis patients responded to the survey. 55.1% of these patients
      knew that they had been screened for BBV and only 12.6% indicated that they had
      received any counselling prior to testing. However, 74.3% answered that they
      would be happy to be tested without consent or counselling. CONCLUSION: The
      majority of the patients had not received adequate information regarding BBV
      screening, but most were content with regular viral screening after initial
      counselling and consent. Information during pre-dialysis sessions may be an
      appropriate way of educating patients about the importance of BBV.

PMID- 19390209
TI  - Cardiorenal risk prevalence in sickle cell hemoglobinopathy.
AB  - INTRODUCTION: The spectrum of kidney functional and structural alterations in
      sickle cell hemoglobinopathy (SCH) is broad. Also, morbidity and mortality from
      end organ dysfunction, especially cardiorenal dysfunction, are substantial.
      Consequently, screening an SCH population prospectively for surrogate markers of
      cardiorenal risk such as albuminuria and intima-media thickness (IMT) was the aim
      of this cross-sectional study. PATIENTS AND METHODS: We screened 165 patients
      with SCH over 4 months at the Primary Care Department, King Abdulaziz Armed
      Forces Hospital, Saudi Arabia. The 133 who fulfilled the inclusion criteria have
      been referred for further investigations. Anthropometric evaluation of body mass
      index (BMI) and blood pressure (BP), determination of 24-hour urine albuminuria,
      fasting lipids, computed atherogenic risk ratio (ARR), estimated glomerular
      filtration rate (eGFR), common carotid artery (CCA) IMT measurements, and
      hemoglobin (Hb) electrophoresis were done. RESULTS: Increased urinary albumin
      excretion (UAE) rate [380 (272.2-489.6) mg/day; mean and 95% confidence interval
      (95% CI) of mean] was detected in 24% of SCH patients (6 males and 26 females).
      Microalbuminuria (168.8 +/- 59.7 mg/day) was noted in the majority (63.6%) while
      macroalbuminuria (752.7 +/- 205.4 mg/day) was detected in a smaller percentage
      (36.4%). Patients with sickle cell disease (SCD) contributed about 66.6% of
      subjects with microalbuminuria and 100% of those with macroalbuminuria, while
      most individuals with sickle cell trait (89%) were normoalbuminuric (p < 0.0001).
      Preclinical atherosclerosis (increased CCA IMT and/or atheromatous plaques) was
      noticed in 68.8% of SCH individuals with increased UAE (ANOVA p = 0.003). The
      microalbuminuric and macroalbuminuric patients had comparable BMI, BP values and
      lipid profiles. However, the microalbuminuric sicklers were significantly younger
      (28.4 +/- 6.7 vs. 34.0 +/- 7.2 years, p = 0.04), less anemic (Hb: 9.13 +/- 2 vs.
      7.47 +/- 0.8 g/dl, p = 0.015), with lesser atherosclerosis (IMT; 0.68 +/- 0.1 vs.
      0.78 +/- 0.1 mm, p = 0.004) and higher eGFR (83.3 +/- 17.2 vs. 61 +/- 10.7
      ml/min/1.73 m(2), p = 0.0004) compared to those with macroalbuminuria. UAE
      correlated positively with age (r = 0.591, p = 0.0001), systolic BP (r = 0.483, p
      = 0.005), IMT (r = 0.399, p = 0.024) and negatively with Hb (r = -0.409, p =
      0.02), and eGFR (r = -0.620, p = 0.0001). By univariate analysis, the significant
      indicators of UAE in SCH patients were age (p = 0.05), BMI (p = 0.041), IMT (p =
      0.018) and eGFR (p = 0.016). Also, increased risk (odds ratio) of albuminuria was
      noted with SCD, age, anemia, abnormal eGFR, obesity, and ARR. CONCLUSIONS:
      Markers of cardiorenal risk such as albuminuria and IMT are common findings in
      SCH patients of Arabic descent and could be useful screening tools to identify
      sicklers at risk for cardiovascular and renal events.

PMID- 19390210
TI  - Utility of cystatin C for assessment of renal function after cardiac surgery.
AB  - BACKGROUND: Though acute renal failure among cardiac surgery patients is
      associated with increased mortality, diagnosis of renal failure is often delayed
      due to the late detectability of laboratory markers for kidney failure. Recently,
      a number of clinical studies have shown that glomerular filtration rate (GFR) can
      be estimated by measuring the serum concentration of cystatin C (CysC). However,
      comparisons between the diagnostic effectiveness of CysC and serum creatinine
      have been inconsistent. The present study compares the diagnostic effectiveness
      of both serum markers in cardiac surgery patients. METHODS: In 50 cardiac surgery
      patients, GFR was quantified by measuring creatinine clearance and estimated from
      serum concentrations of both creatinine and CysC. The sensitivity and specificity
      of serum creatinine and CysC for detection of reduced GFR values were compared as
      well as correlation between estimated GFR values and creatinine clearance.
      RESULTS: GFR values <60 ml/min/1.73 m(2) were detected with equal effectiveness
      using creatinine or CysC, whereas for the detection of GFR <90 ml/min/1.73 m(2)
      the area under the curve of serum creatinine was significantly higher.
      Correlation between estimated GFR values and creatinine clearance was higher when
      creatinine-based formulae were used. CONCLUSION: In patients after cardiac
      surgery, CysC is not superior to serum creatinine for assessment of GFR.

PMID- 19390211
TI  - Tubular proteinuria and glomerular filtration 6 years after puumala hantavirus
      induced acute interstitial nephritis.
AB  - BACKGROUND/AIMS: We previously found increased urinary protein excretion,
      glomerular filtration rate (GFR) and blood pressure in a retrospective analysis
      of patients with previous nephropathia epidemica (NE). Here, we evaluated the
      long-term outcome after NE in a prospectively recruited patient group. METHODS:
      Proteinuria, GFR and ambulatory 24-hour blood pressure were assessed 4-7 years
      (mean 6) after acute NE in 37 patients, and these values were compared to those
      from 38 seronegative controls. RESULTS: Six years after NE, the prevalence of
      elevated urinary alpha(1)-microglobulin excretion was higher in the patients than
      controls (9/35 vs. 1/38; p = 0.005). The patients also had higher urinary protein
      excretion (0.17 +/- 0.05 vs. 0.14 +/- 0.04 g/day; p = 0.006), GFR (119 +/- 19 vs.
      109 +/- 14 ml/min/1.73 m(2); p = 0.016) and mean systolic (123 +/- 11 vs. 117 +/-
      9 mm Hg; p = 0.012), nighttime systolic (109 +/- 11 vs. 100 +/- 9 mm Hg; p =
      0.001) and nighttime diastolic blood pressure (70 +/- 7 vs. 66 +/- 7 mm Hg; p =
      0.035) than the controls. CONCLUSIONS: These results confirm our previous
      findings of a higher prevalence of tubular proteinuria and increased urinary
      protein excretion, GFR and systolic blood pressure 6 years after acute NE.

PMID- 19390212
TI  - Overweight, obesity and chronic kidney disease.
AB  - The sharp rise in the prevalence of chronic kidney disease (CKD) that parallels
      an increase in the prevalence of obesity in the recent years is a cause for great
      concern. CKD increases the rate of cardiovascular disease (CVD), development of
      end-stage renal disease, and leads to premature death. Although no direct
      causality link between obesity and CKD can yet be established, this appears
      highly likely. CKD should be regarded as a major complication of overweight and
      obesity, regardless of whether the association was independent or through the
      influence of diabetes, hypertension, CVD, metabolic syndrome and high fructose
      intake. We review the literature on the complex but positive association between
      obesity and CKD, the pathological effect of excess adiposity in kidney injury and
      the potential role of weight reduction therapy in reducing the burden of CKD.

PMID- 19390213
TI  - Chronic kidney disease-related mineral and bone disorders.
AB  - The clinical practice guidelines, their scope, limitations and applicability
      within the field of mineral and bone disorders have been analyzed. The different
      available guidelines have been compared and their content has been put into the
      perspective of the user. The aim has been to review their accuracy and relevance
      for the key set of mineral and bone disorders, and not to attempt to rewrite them
      or provide new guidelines based on the authors' feelings and experience.

PMID- 19390214
TI  - Inferring disease mechanisms from epidemiological data in chronic kidney disease:
      calcium and phosphorus metabolism.
AB  - BACKGROUND/AIMS: By applying numerical filtering to epidemiological data of 2,512
      chronic kidney disease patients, we aimed to identify some of the underlying
      mechanisms of the calcium/phosphorus metabolism perturbations. METHODS: The
      measured variables, serum calcitriol, calcidiol, total calcium ([Ca](s)) and
      phosphorus ([P](s)) and the urinary excretions of calcium and phosphorus, were
      paired in the same patients with the glomerular filtration rate (GFR) or the
      serum concentrations of parathormone (i[PTH](s)) (used as independent variables)
      numerically filtered with a moving average and partitioned into 15-25 frequency
      classes. All variables exhibited unimodal frequency distributions. RESULTS: There
      was a steep fall of i[PTH](s), [P](s), and urinary excretion fractions of Ca and
      P up to a value of GFR in the range of 25-45 ml/min/1.73 m2. The increase in the
      phosphorus urinary excretion preceded the steep increase in i[PTH](s). Except
      [Ca](s), all factors exhibited their physiological correlation with i[PTH](s)
      when GFR was above 90 ml/min/1.73 m2 and reverted to a feedback correlation below
      80 ml/min/1.73 m2. CONCLUSION: The perturbation of mineral metabolism in chronic
      kidney disease results in the maintenance of a normal range of [Ca](s) and [P](s)
      acting as the controlled factors at the cost of large variations of i[PTH](s),
      and calcium and phosphate urinary excretions behaving as controlling factors.

PMID- 19390215
TI  - Urinary fatty acids and liver-type fatty acid binding protein in diabetic
      nephropathy.
AB  - BACKGROUND: The aims of this clinical study were to investigate the associations
      of urinary free fatty acid (FFA) levels with tubulointerstitial damage, and to
      determine the clinical significance of urinary liver-type fatty acid binding
      protein (L-FABP) in diabetic nephropathy. METHODS: Fifteen patients with
      nephrotic syndrome due to diabetic nephropathy and 12 patients with minimal
      change nephrotic syndrome (MCNS) were studied. Urinary and serum FFA
      concentrations (palmitic, oleic, linoleic, and arachidonic acids) were measured
      by gas chromatography, and urinary L-FABP levels were quantified using an ELISA
      technique. Tubulointerstitial damage was assessed using renal biopsy specimens.
      RESULTS: The levels of urinary linoleic and arachidonic acids were significantly
      elevated in diabetic nephropathy compared to MCNS patients, though serum FFA
      levels were lower in diabetic nephropathy than MCNS patients. The degree of
      tubulointerstitial damage was significantly severer in the patients with diabetic
      nephropathy than MCNS. Urinary L-FABP and 8-OHdG (8-hydroxydeoxyguanosine)
      concentrations were significantly higher in the diabetic nephropathy subjects.
      CONCLUSION: Elevated urinary excretion of FFA may be a reflection of FFA overload
      in the proximal tubules, and FFA may be an important promoter of
      tubulointerstitial damage in diabetic nephropathy patients. Urinary L-FABP levels
      may reflect the stress induced by FFA to the proximal tubules, leading to severe
      tubulointerstitial damage.

PMID- 19390216
TI  - Infected hepatic and renal cysts: differential impact on outcome in autosomal
      dominant polycystic kidney disease.
AB  - BACKGROUND: Infected cysts are a frequent and serious complication of autosomal
      dominant polycystic kidney disease. Such infections are classified into those
      affecting hepatic cysts and those affecting renal cysts. The purpose of this
      study was to compare the clinical course of infected hepatic cysts with that of
      infected renal cysts in patients with autosomal dominant polycystic kidney
      disease. METHODS: We analyzed 43 patients referred to us for additional treatment
      of severely infected cysts between January 2004 and December 2006. All patients
      who required further treatment in addition to antibiotic therapy were included.
      RESULTS: Aspiration was performed in all 28 patients with infected hepatic cysts.
      As a result, 17 patients were cured, 4 remain under treatment, and 6 died. One
      patient was cured by partial hepatectomy. Among the 15 patients with renal cysts,
      aspiration was performed in 4 with identifiable infected cysts, while renal
      transcatheter arterial embolization after appropriate antibiotic therapy was
      performed in 11 without identifiable infected cysts. No patient developed
      recurrence. CONCLUSION: In patients with infected renal cysts, aspiration or
      renal transcatheter arterial embolization after appropriate antibiotic therapy
      was effective. Although aspiration was often effective in patients with infected
      hepatic cysts, a good outcome was less likely than in those with renal cysts.

PMID- 19390217
TI  - The search for a new marker of renal function in older patients with chronic
      kidney disease stages 3-4: usefulness of cystatin C-based equations.
AB  - BACKGROUND/AIM: Cystatin C (Cys C) is an endogenous marker of glomerular
      filtration rate (GFR) unaffected by body composition. The aim of the present
      study was to assess the utility of Cys C-based GFR prediction equations (Hoek,
      Larsson and Stevens) and creatinine (modification of diet in renal disease
      isotope dilution mass spectrometry--MDRD-IDMS, and Cockcroft-Gault--CG) compared
      with 51Cr-EDTA. METHODS: This study was carried out in 40 Caucasian older
      patients with advanced age (> or = 60) and chronic kidney disease stages 3-4. To
      assess the utility of prediction equations in relation to body composition, we
      measured lean mass (LM) with densitometry (DXA). Pearson's, Bland-Altman and
      Lin's coefficient (Rc) were used to study accuracy and precision. RESULTS: 51Cr
      EDTA was 36.9 +/- 9.2 ml/min/1.73 m2 (22-60). Cys C levels were 2.2 +/- 0.8 mg/l
      (r = 0.085; p = 0.662 LM) and creatinine 2.8 +/- 1.1 mg/dl (r = 0.427; p = 0.021
      LM). The most accurate equations were the Hoek, Larsson and Stevens formulae,
      with a bias of -0.2 (Rc 0.48), -2.9 (Rc 0.44) and 2.6 ml/min/1.73 m2 (Rc 0.58).
      The biases obtained with MDRD-IDMS and CG were -14.6 (Rc 0.35) and -12.5 (Rc
      0.40). All correlations among biases obtained with creatinine-based formulae and
      LM were negative and statistically significant (p < 0.05). CONCLUSIONS: The
      results show superiority of Cys C-based GFR formulae over the MDRD-IDMS and CG
      equations. This significant underestimation obtained with conventional prediction
      equations was directly related to the influence of LM.

PMID- 19390218
TI  - P wave dispersion increases during hemodialysis sessions.
AB  - BACKGROUND/AIMS: Atrial fibrillation (AF) is common among hemodialysis (HD)
      patients and is associated with high mortality. P wave dispersion (PWD) is a
      noninvasive electrocardiographic marker of paroxysmal AF. Our aim was to evaluate
      the effect of HD session on PWD. METHODS: Twenty-five patients (mean age 63
      years, 10 males) with sinus rhythm and undergoing chronic HD treatment were
      included. Blood samples were drawn and 12-lead electrocardiograms were recorded
      immediately before HD session, at the 2nd hour during HD and at the end of the HD
      session. The difference between maximum and minimum P wave durations was
      calculated as PWD. RESULTS: PWD significantly increased during HD sessions
      compared with predialysis values (41 +/- 12 vs. 21 +/- 10 ms, respectively, p <
      0.001), then decreased to a value of 24 +/- 7 ms at the completion of HD, which
      was not significantly different from the predialysis values. PWD during HD was
      significantly correlated with predialysis systolic and diastolic blood pressure
      (r = 0.42, p = 0.037, and r = 0.59, p = 0.002, respectively) and predialysis
      serum potassium level (r = 0.44, p = 0.031). Linear regression model revealed
      that predialysis diastolic blood pressure (p = 0.002), predialysis serum
      potassium level (p = 0.037) and the amount of ultrafiltration (p = 0.048) were
      the significant predictors of prolonged PWD during HD. CONCLUSION: PWD increases
      significantly during HD sessions. This may increase the risk of AF episodes
      during HD. High diastolic blood pressure and serum potassium level before HD and
      ultrafiltration amount may predict prolonged PWD during HD.

PMID- 19390219
TI  - Microarray and bioinformatics analysis of gene expression in experimental
      membranous nephropathy.
AB  - BACKGROUND: Passive Heymann nephritis (PHN), the best characterized animal model
      of experimental membranous nephropathy, is characterized by subepithelial immune
      deposits, podocyte foot processes effacement and massive proteinuria beginning 4
      days following disease induction. Although single genes involved in PHN have been
      studied, no whole genome-wide expression analysis of kidney tissue has been
      performed. METHODS: Microarray analysis was performed to identify gene expression
      changes in PHN rat kidneys during the onset of proteinuria. RESULTS: Our results
      showed that 234 transcripts were differentially expressed in diseased animals
      compared to controls. Genes exclusively upregulated in diseased animals were
      mainly required for cell structure and motility, immunity and defense, cell
      cycle, and developmental processes. The single most increased gene was transgelin
      (Tagln) showing a 70-fold upregulation in animals with PHN. Protein-protein
      interaction analysis revealed the following four processes of major relevance in
      disease manifestation: (i) DNA damage and repair; (ii) changes in the
      extracellular matrix; (iii) deregulation of cytokines and growth factors, as well
      as (iv) rearrangements of the cytoskeleton. CONCLUSION: We show for the first
      time the complex interplay between multiple different genes in experimental
      membranous nephropathy, supporting a role for genomic approaches to better
      understanding and defining specific disease processes.

PMID- 19390220
TI  - Mizoribine suppresses the progression of experimental peritoneal fibrosis in a
      rat model.
AB  - BACKGROUND/AIMS: Peritoneal fibrosis is a serious complication of peritoneal
      dialysis (PD). It has been reported that administration of mizoribine, an
      effective immunosuppressant, ameliorated renal fibrosis in a rat model of
      unilateral ureteral obstruction. We therefore examined the effects of mizoribine
      in an experimental model of peritoneal fibrosis. METHODS: 24 rats were given a
      daily intraperitoneal injection of chlorhexidine gluconate and ethanol dissolved
      in saline. The rats were divided into three groups (n = 8 per group) that
      received either vehicle or mizoribine at a dose of 2 or 8 mg/kg once a day. 28
      days after the start of the treatments the rats were sacrificed and peritoneal
      tissue samples collected. Macrophage infiltration (ED1), myofibroblast
      accumulation (alpha-smooth muscle actin (SMA)) and expression of type III
      collagen, transforming growth factor (TGF)-beta and monocyte chemotactic protein
      1 (MCP-1) were examined by immunohistochemistry. RESULTS: Mizoribine
      significantly suppressed submesothelial zone thickening and reduced macrophage
      infiltration. Mizoribine also reduced collagen III(+) area and decreased the
      number of alpha-SMA(+), TGF-beta(+) and MCP-1(+) cells. The magnitude of the
      changes observed was dose-dependent. CONCLUSION: The administration of mizoribine
      prevented the progression of peritoneal fibrosis in this rat model. Mizoribine
      may represent a novel therapy for peritoneal sclerosis in patients undergoing
      long-term PD.

PMID- 19390221
TI  - OCRL1 mutations in Dent 2 patients suggest a mechanism for phenotypic
      variability.
AB  - BACKGROUND/AIMS: Dent disease is an X-linked renal proximal tubulopathy
      associated with mutations in CLCN5 (Dent 1) or OCRL1 (Dent 2). OCRL1 mutations
      also cause the oculocerebrorenal syndrome of Lowe. METHODS: Dent patients with
      normal sequence for CLCN5 were sequenced for mutations in OCRL1. By analyzing
      these and all other OCRL1 mutations reported, a model relating OCRL1 mutations to
      the resulting disease (Dent 2 or Lowe's) was developed. RESULTS: Six boys with
      Dent disease had novel OCRL1 mutations: two missense (R301H, G304E) and four
      mutations predicted to produce premature termination codons (L56DfsX1, S149X,
      P161PfsX3, and M170IfsX1). These include one of the original patients reported by
      Dent and Friedman. Slit lamp examinations revealed early cataracts in only one
      boy with normal vision. None of these Dent 2 patients had metabolic acidosis; 3
      had mild mental retardation. Analysis of all known OCRL1 mutations show that Dent
      2 mutations fall into two classes that do not overlap with Lowe mutations.
      Bioinformatics analyses identified expressed OCRL1 splice variants that help
      explain the variability of those clinical features that distinguish Dent disease
      from Lowe syndrome. CONCLUSIONS: OCRL1 mutations can cause the renal phenotype of
      Dent disease, without acidosis or the dramatic eye abnormalities typical of Lowe
      syndrome. We propose a model to explain the phenotypic variability between Dent 2
      and Lowe's based on distinctly different classes of mutations in OCRL1 producing
      splice variants.

PMID- 19390222
TI  - Expression and activity of SGLT2 in diabetes induced by streptozotocin:
      relationship with the lipid environment.
AB  - BACKGROUND/AIMS: Diabetes mellitus may impact on the regulation of renal Na+
      glucose cotransporter type 2 (SGLT2), however, previous studies have yielded
      conflicting results on the effects of streptozotocin (STZ)-induced diabetes on
      SGLT-mediated glucose transport. METHODS: Diabetes was induced in male Wistar
      rats. The studies were performed at 3 (D3), 7 (D7) and 14 (D14) days after a
      single i.p. injection of STZ. SGLT2 activity was measured using alpha-14C-methyl
      glucose uptake in brush-border vesicles (BBV) from renal cortex, and SGLT2
      expression was assessed by immunoblotting. Phospholipids were quantified by a
      modification of Fiske-Subarow's method after being separated by thin-layer
      chromatography. RESULTS: Glucose uptake was reduced in all groups of diabetic
      rats. SGLT2 expression decreased in D3 and D7. There was a decrease in
      sphingomyelin (SM) content and an increase in phosphatidylcholine (PC) content in
      BBV from D14 versus control, without differences in phosphatidylinositol (PI),
      phosphatidylserine (PS) and phosphatidylethanolamine (PE). CONCLUSION: The
      downregulation of SGLT2 activity during STZ-induced diabetes may be a protective
      mechanism to control the excess of circulating glucose and could be a consequence
      of a decrease in SGLT2 expression in D3 and D7, whereas altered activity of SGLT2
      in D14 could be a consequence of changes in membrane lipid composition. However,
      we cannot discard the possibility that the decrease in SGLT2 activity could be
      due to a covalent modification of the active site of the protein.

PMID- 19390223
TI  - Cytokine changes and tryptophan metabolites in medication-naive and medication
      free schizophrenic patients.
AB  - Cytokine imbalances especially between T helper type (Th) 1 and Th2 and
      tryptophan breakdown were reported to be involved in the pathophysiology of
      schizophrenia. The hyperactive inflammatory response system could induce enhanced
      tryptophan breakdown. This study aimed to investigate the relationship between
      cytokine changes, tryptophan breakdown parameter changes and clinical parameters
      in patients with schizophrenia in comparison with normal controls. In the plasma
      of schizophrenic patients, Th1-specific interferon-gamma was significantly higher
      (F = 7.485, p = 0.007) and Th2-specific interleukin (IL)-4 was significantly
      lower (F = 126.327, p < 0.0001). The Th1-related cytokine IL-2 was lower (F =
      5.409, p = 0.021) but tumor necrosis factor-alpha (TNF-alpha) and Th2-related IL
      6 were higher (F = 95.004, p < 0.0001 and F = 408.176, p < 0.0001, respectively)
      in the plasma of schizophrenic patients. After 6 weeks of treatment, IL-6 and TNF
      alpha were significantly reduced (t = -3.762, p < 0.0001 and z = -2.668, p =
      0.008). At the time of admission, plasma tryptophan concentrations were lower (F
      = 6.339, p = 0.012) in schizophrenic patients and were negatively correlated with
      the total positive symptoms score (r(2) = -0.343, p = 0.004). After 6 weeks of
      medication, both plasma tryptophan and kynurenine concentrations were increased
      (t = -2.937, p = 0.005 and t = -3.214, p = 0.002, respectively). The findings of
      this study indicate a hyperactive pro-inflammatory response inducing a change in
      tryptophan metabolism that might be related to the development of positive
      symptoms in schizophrenia.

PMID- 19390224
TI  - Dopamine D2 receptor gene polymorphisms are associated with suicide attempt in
      the Japanese population.
AB  - BACKGROUND: Some reports have suggested the involvement of the D2 dopaminergic
      function in the expression of suicidal behavior. Here, we examined associations
      between suicide attempts and two kinds of functional polymorphisms in the
      dopamine D2 receptor (DRD2) gene, namely, TaqIA and -141C Ins/Del. METHODS:
      Subjects included 120 suicide attempters and 123 unrelated volunteers. Those who
      attempted suicide were severely injured and were transferred to the emergency
      unit in our university hospital. To determine each genotype, we performed
      polymerase chain reaction and restriction fragment length polymorphism analyses.
      RESULTS: We found significant differences in genotypic and allelic frequencies of
      -141C Ins/Del and TaqIA polymorphisms between suicide attempters and healthy
      controls (-141C Ins/Del, p = 0.01; TaqIA,p = 0.036). The Ins allele of -141C
      Ins/Del was significantly more frequent in suicide attempters (p = 0.011), as
      well as the A2 allele of TaqIA (p = 0.017). Haplotype analysis revealed no
      significant linkage disequilibrium between -141C Ins/Del and TaqIA polymorphisms
      (D' = 0.226, r(2) = 0.016, p = 0.10). CONCLUSIONS: These findings suggest that
      DRD2 gene polymorphisms may be involved in the biological susceptibility to
      suicide.

PMID- 19390225
TI  - Lasting resolution of diabetic macular edema and stable improvement of visual
      acuity after treatment with pars plana vitrectomy.

PMID- 19390226
TI  - A case of congenital orbital malignant rhabdoid tumor: systemic metastasis
      following exenteration.
AB  - A newborn girl presented with massive proptosis of the right eye. Physical and
      radiologic examination disclosed that the primary orbital mass was confined to
      the site. A diagnosis of malignant rhabdoid tumor was made by histopathologic
      examination of an incisional biopsy specimen. Exenteration was performed, and the
      resection margins were free from tumor cells. However, distant metastasis
      developed in the liver 1 month after surgery. Despite chemotherapy, the patient
      died 2 months later due to tumor invasion into the central nervous system, which
      was confirmed by autopsy. To the best of our knowledge, this is the first case of
      congenital orbital malignant rhabdoid tumor showing systemic metastasis after
      exenteration, which suggests the need for aggressive systemic treatment rather
      than exenteration, even in a case of locally confined tumor.

PMID- 19390227
TI  - Large subretinal haemorrhage following change from intravitreal bevacizumab to
      ranibizumab.
AB  - BACKGROUND: To report 2 cases of large subretinal haemorrhage in 2 patients with
      age-related macular degeneration when the intravitreal injections were changed
      from bevacizumab (Avastin) to ranibizumab (Lucentis). METHODS: Both patients were
      treated initially with intravitreal bevacizumab 1.25 mg for 4 months (4
      injections) and then switched to 0.5 mg ranibizumab which continued for another 6
      months. Best-corrected visual acuity measurements, slit-lamp examination, contact
      lens biomicroscopy, optical coherence tomography and fluorescein angiography were
      performed at baseline examination and every month. RESULTS: Both patients showed
      initial improvement when treated with intravitreal bevacizumab followed by
      deterioration and development of a large subretinal haemorrhage when changing to
      intravitreal ranibizumab. CONCLUSIONS: There is not enough experience switching
      from one anti-vascular-endothelial-growth-factor agent to another. A prospective
      study with large series of patients and controls may be necessary in order to
      determine whether it is safe enough to change from one medication to another.

PMID- 19390228
TI  - Rhythm as an affordance for the entrainment of movement.
AB  - A general account of rhythm in human behaviour is provided, according to which
      rhythm inheres in the affordance that a signal provides for the entrainment of
      movement on the part of a perceiver. This generic account is supported by an
      explication of the central concepts of affordance and entrainment. When viewed in
      this light, rhythm appears as the correct explanandum to account for coordinated
      behaviour in a wide variety of situations, including such core senses as dance
      and the production of music. Speech may appear to be only marginally rhythmical
      under such an account, but several experimental studies reveal that speech, too,
      has the potential to entrain movement.

PMID- 19390229
TI  - Rhythm in speech and language: a new research paradigm.
AB  - Like any other aspect of spoken language, rhythm needs to be, and has been,
      studied from four different perspectives for a comprehensive and insightful
      account of its nature and functioning in speech communication: symbolic
      representation, production, perception, communicative function. The paper first
      gives an overview of the milestones in the analysis of rhythm under the headings
      of these four approaches over the past 70 years. This survey of the development
      of scientific ideas in rhythm research prepares the ground for the integration of
      the four strands in an interrelated framework of linguistic and speech signal
      analysis. On the basis of a definition of rhythm derived from the theoretical and
      methodological discussion, a new paradigm is outlined for future research,
      centred on the listener and on communicative function.

PMID- 19390230
TI  - Rhythm, timing and the timing of rhythm.
AB  - This article reviews the evidence for rhythmic categorization that has emerged on
      the basis of rhythm metrics, and argues that the metrics are unreliable
      predictors of rhythm which provide no more than a crude measure of timing. It is
      further argued that timing is distinct from rhythm and that equating them has led
      to circularity and a psychologically questionable conceptualization of rhythm in
      speech. It is thus proposed that research on rhythm be based on the same
      principles for all languages, something that does not apply to the widely
      accepted division of languages into stress- and syllable-timed. The hypothesis is
      advanced that these universal principles are grouping and prominence and evidence
      to support it is provided.

PMID- 19390231
TI  - The Pairwise Variability Index and coexisting rhythms in language.
AB  - The Pairwise Variability Index (PVI) has been widely used as a metric for
      quantifying rhythm in languages, often with a view to placing them on a continuum
      between notional categories of stress-timing and syllable-timing. We review the
      history of and rationale for the PVI, and point out three potential anomalies in
      the way the PVI has been applied. Following up one of these we apply the PVI to
      the level of the foot, and argue that stress-timing and syllable-timing are not
      points at either end of a continuum but orthogonal dimensions, so that a language
      can be (for instance) both syllable-timed and stress-timed. Results from
      Estonian, English, Mexican Spanish, and Castilian Spanish are presented which
      give some support for this view.

PMID- 19390232
TI  - Do rhythm measures reflect perceived rhythm?
AB  - In a production study, Bulgarian, English and German verses with regular poetic
      metrical metres of different types and elicited prose utterances with varied
      accentual patterns are produced in textual and iterative (dada) form and measured
      at syllable level according to the pairwise variability index (PVI) principle.
      Systematic differences in PVI values show that the measure is sensitive to
      metrical differences. But variations for utterances with the same metrical
      structure and comparable measures for accentually different utterances show the
      measure to be insensitive to the temporal distribution of accents. A perceptual
      experiment with Bulgarian, English and German subjects confirms the hypothesis
      that the perceived strength of rhythmicity in a line of verse is determined not
      only by its temporal structure, but also by other acoustic properties, most
      clearly by F(0) change within the metrical foot.

PMID- 19390233
TI  - F0-based rhythm effects on the perception of local syllable prominence.
AB  - A perception experiment shows for German that different global, F(0)-based speech
      rhythms in the context section of stimuli influence the local prominence position
      in the target section. This effect may be conceptualized as a perceptual
      adjustment of the syllables in the target section to the ones of the global
      rhythmic context with regard to both the prominence and the F(0) patterns. Two
      conclusions were drawn on this basis. First, listeners use speech rhythm to
      predict the perceptual properties of syllables, which is in line with the guide
      function that speech rhythm is assumed to have in German and other Western
      Germanic languages. Secondly, speech rhythm is a perceptual phenomenon, generated
      by a cyclic construction process that involves repetitive patterns in multiple
      dimensions. Thus, although speech rhythm is initiated by changes in acoustic
      parameters, it cannot be soaked up by acoustic measurements, especially, if these
      measurements refer to duration alone.

PMID- 19390234
TI  - On the possible role of brain rhythms in speech perception: intelligibility of
      time-compressed speech with periodic and aperiodic insertions of silence.
AB  - This study was motivated by the prospective role played by brain rhythms in
      speech perception. The intelligibility - in terms of word error rate - of natural
      sounding, synthetically generated sentences was measured using a paradigm that
      alters speech-energy rhythm over a range of frequencies. The material comprised
      96 semantically unpredictable sentences, each approximately 2 s long (6-8 words
      per sentence), generated by a high-quality text-to-speech (TTS) synthesis engine.
      The TTS waveform was time-compressed by a factor of 3, creating a signal with a
      syllable rhythm three times faster than the original, and whose intelligibility
      is poor (<50% words correct). A waveform with an artificial rhythm was produced
      by automatically segmenting the time-compressed waveform into consecutive 40-ms
      fragments, each followed by a silent interval. The parameters varied were the
      length of the silent interval (0-160 ms) and whether the lengths of silence were
      equal ('periodic') or not ('aperiodic'). The performance curve (word error rate
      as a function of mean duration of silence) was U-shaped. The lowest word error
      rate (i.e., highest intelligibility) occurred when the silence was 80 ms long and
      inserted periodically. This is also the condition for which word error rate
      increased when the silence was inserted aperiodically. These data are consistent
      with a model (TEMPO) in which low-frequency brain rhythms affect the ability to
      decode the speech signal. In TEMPO, optimum intelligibility is achieved when the
      syllable rhythm is within the range of the high theta-frequency brain rhythms (6
      12 Hz), comparable to the rate at which segments and syllables are articulated in
      conversational speech.

PMID- 19390235
TI  - HPV 16 E2 protein induces apoptosis in human and murine HPV 16 transformed
      epithelial cells and has antitumoral effects in vivo.
AB  - OBJECTIVE: Our aims were to examine the ability of the human papillomaviruse
      (HPV) 16 E2 protein to induce apoptosis in a murine HPV-transformed cell line,
      and to evaluate its antitumor properties on HPV-associated tumors in vivo in
      immunocompetent mice. METHODS: HPV-transformed murine BMK-16/myc cells and human
      SiHa cells were transfected with the HPV 16 E2 gene to examine the effects of the
      E2 protein on cell growth and on the E6 and E7 oncogenes as well as DNA
      fragmentation and activation of the extrinsic pathway of apoptosis. Finally, to
      test the antitumor effect of the E2 protein on an experimental mouse tumor model,
      we generated a recombinant adenovirus expressing the E2 protein. RESULTS: The E2
      protein inhibited the growth of SiHa and BMK-16/myc cell lines, and repressed the
      E6 and E7 oncogenes. Moreover, the E2 protein induced DNA fragmentation and
      apoptosis through activation of caspases 8 and 3 in BMK-16/myc cells. On the
      other hand, E2 also showed antitumor effects in vivo. CONCLUSIONS: Our findings
      indicate that E2 exerts pro-apoptotic activity in a murine HPV-transformed cell
      line as well as an antitumor effect in vivo.

PMID- 19390236
TI  - Sublingual immunotherapy for Japanese cedar pollinosis.
AB  - The prevalence of pollinosis caused by cedar pollen has increased by 10% these
      ten years of 26.5% in the investigation of 2008 in Japan. The pharmacotherapy is
      a main treatment tool for pollinosis, and the surgical treatment is not
      acknowledged to the treatment of pollinosis internationally. Moreover, allergen
      immunotherapy enters a special treatment method, and is an important therapeutic
      procedure. The allergen immunotherapy is unique for having possibility of curing
      allergen specific allergic diseases. However the side effect of allergen
      subcutaneous immunotherapy (SCIT), such as anaphylaxis is kept at a distance in a
      medical situation in Japan. Then, a sublingual immunotherapy (SLIT) that was
      safer than it, developed in Europe for pollinosis induced by grass or ragweed,
      but not in Japan. As a result, the effect of SLIT was proven in the cedar
      pollinosis in Japan as high level evidence. A whole body immunity induction is
      thought in the appearance of the effect, and, in addition, it is necessary to be
      going to be cleared the accurate mechanism of the effect in the future. Moreover,
      the development of a special SLIT and the import of an overseas product are
      needed in Japan.

PMID- 19390237
TI  - Biomarkers for allergen immunotherapy in cedar pollinosis.
AB  - To initiate, monitor, and complete effective immunotherapy, biomarkers to predict
      and visualize the immune responses are needed. First, we need to identify the
      right candidate for immunotherapy. Secondly, the immune responses induced by
      immunotherapy should be monitored. For the first objective, analysis of
      polymorphisms of candidate genes may be helpful, but still be in development.
      Regarding biomarkers for immune responsese, there are numerous reports that
      evaluate immunotherapy-induced immune changes such as suppression of effector
      cells, deviation to Th1 cytokine production, and induction of regulatory T cells.
      No standardized methods, however, have been established. Among them, a functional
      assay of blocking IgG activity, the IgE-facilitated allergen binding assay, may
      be useful. We quantitated induced expression of an activation marker, CD203c, on
      basophils and found that the assay efficiently predicts sensitivity to particular
      allergen and severity of the allergen-induced symptoms. In patients who received
      rush immunotherapy for Japanese cedar pollinosis, reduction in CD203c expression
      after the therapy was observed, suggesting the utility of the test for monitoring
      immunotherapy.

PMID- 19390238
TI  - Effects of KF19514, a phosphodiesterase 4 and 1 Inhibitor, on bronchial
      inflammation and remodeling in a murine model of chronic asthma.
AB  - BACKGROUND: Phosphodiesterase 4 selective inhibitor may prevent airway
      inflammation and remodeling. OBJECTIVE: The aim of this study was to investigate
      the effects of KF19514, a phosphodiesterase 4 and 1 dual inhibitor, on chronic
      airway inflammation and remodeling following chronic exposure to aerosolized
      antigen in mice. METHODS: Ovalbumin (OVA) was administered intraperitoneally to
      BALB/c mice on days 0 and 14, and the mice were then exposed to aerosolized OVA
      daily for 4 weeks. Twenty-four hours following the final inhalation, bronchial
      responsiveness to acetylcholine was measured, and histologic examination and
      hydroxyproline content of the lung were evaluated. RESULTS: Bronchial
      responsiveness to acetylcholine, number of inflammatory cells and eosinophils in
      the lamina propria, thickness of epithelial and subepithelial collagen layers,
      and hydroxyproline content of the lung increased following chronic exposure to
      OVA for 7 weeks. KF19514 significantly prevented all of these changes.
      CONCLUSIONS: Phosphodiesterase 4 and 1 inhibitors such as KF19514 may help
      prevent bronchial hyperresponsiveness and chronic asthma-induced airway
      remodeling.

PMID- 19390240
TI  - Clinical evaluation of severe asthma attacks requiring tracheal intubation and
      mechanical ventilation.
AB  - BACKGROUND: Although the number of patients requiring hospitalization due to
      asthma attacks has decreased over the years, there are many who still require
      hospitalization for tracheal intubation and mechanical ventilation following a
      severe asthma attack. Therefore, we evaluated the characteristics of patients
      with asthma who required tracheal intubation and mechanical ventilation in our
      hospital. METHODS: We evaluated 20 patients who had severely exacerbated asthma,
      requiring tracheal intubation and mechanical ventilation. An evaluation was made
      based on their smoking history, the number of days from the onset of the asthma
      attack to admission, the level of asthma control, treatments before presenting to
      our hospital, the frequency of hospital visits, the reason for tracheal
      intubation and mechanical ventilation, and outcome. RESULTS: Of the 20 patients
      with asthma 13 were men and 7 women, with a mean age of 48.7 years. The
      characteristics of patients who required tracheal intubation and mechanical
      ventilation were as follows: (1) smokers, (2) not taking or irregularly taking
      medication, (3) using inhaled short-acting beta(2)agonist (SABA) alone as needed,
      and (4) not using inhaled corticosteroids (ICS). CONCLUSIONS: Our findings
      suggest that treatment mainly using ICS, in addition to increased awareness of
      the dangers of asthma among the patients themselves, are important in preventing
      severe asthma attacks requiring tracheal intubation and mechanical ventilation.

PMID- 19390239
TI  - Effects of pranlukast hydrate on airway hyperresponsiveness in non-asthmatic
      patients with Japanese cedar pollinosis.
AB  - BACKGROUND: Recent studies have suggested that allergic rhinitis is closely
      related to bronchial asthma, reflecting the "one airway-one disease" hypothesis.
      It is unclear if the effects of pranlukast, a leukotriene-receptor antagonist,
      are consistent with this hypothesis. OBJECTIVE: The goal of the study was to
      determine if pranlukast has effects on the upper and lower airways through a
      comparison of the effects of fexofenadine and pranlukast on airway
      hyperresponsiveness in non-asthmatic patients with cedar pollinosis before the
      Japanese cedar pollen season and during the peak pollen season. METHODS: Patients
      received fexofenadine hydrochloride plus oral mequitazine (fexofenadine group) or
      pranlukast hydrate plus oral mequitazine (pranlukast group) as an initial
      treatment. Subsequent changes in airway responsiveness to acetylcholine were
      measured. RESULTS: Among patients in whom coughing developed during the peak
      pollen season, airway responsiveness significantly increased in the fexofenadine
      group. In the pranlukast group, airway responsiveness did not increase
      significantly, regardless of the presence or absence of coughing. CONCLUSIONS:
      The results indicate that pranlukast hydrate inhibits airway hyperresponsiveness
      in non-asthmatic patients with Japanese cedar pollinosis. In turn, this suggests
      that cysteinyl leukotrienes have a role in increased airway responsiveness.

PMID- 19390241
TI  - Comparison of allergenic properties of salmon (Oncorhynchus nerka) between
      landlocked and anadromous species.
AB  - BACKGROUND: Salmon is one of the most widely consumed seafoods in Japan and many
      other countries around the world. Due to the confirmed cases of salmon-induced
      allergy, the food sanitation law in Japan stipulates salmon as one of the
      specific food items for which labeling is recommended when used as an ingredient
      of processed foods. However, trout, the landlocked form of anadromous salmon, is
      not subject to the allergen-labeling requirements, even though both populations
      belong to a single species. Since no supporting data have been demonstrated to
      make a clear distinction between these two populations in terms of allergenicity,
      we comparatively examined their allergenic properties using sera from patients
      allergic to fish. METHODS: Extracts of Oncorhynchus nerka from different habitats
      were obtained: kokanee (landlocked) and red salmon (anadromous). Control extracts
      were derived from four other species. This study focused on the (1) IgE-binding
      capacity of the fish extracts in patients' sera (n = 50), (2) ELISA inhibition
      test (n = 6), and (3) inhibition immunoblot test (n = 8) between the kokanee and
      red salmon. RESULTS: The extracts from kokanee and red salmon showed the highest
      correlation with each other in terms of the IgE-binding capacity, and showed
      complete (100%) reciprocal cross-inhibition in the ELISA inhibition test. On
      immunoblotting, there was no marked difference in the staining pattern between
      the two extracts, and each IgE-binding band gradually disappeared when the
      patients' sera were preincubated with the counterpart antigen in a dose-dependent
      manner. CONCLUSIONS: These results suggest that kokanee has similar allergenic
      properties to red salmon.

PMID- 19390242
TI  - Inflammation, but not hypoxia, mediated HIF-1alpha activation depends on COX-2.
AB  - The COX pathway has been a target for pharmaceutical intervention in diseases
      with a high inflammatory component ranging from asthma and Alzheimer's to
      arthritis and cancer. A major transcriptional promoter of the malignant
      phenotype, HIF-1alpha, has been observed to be regulated by the COX-2 product
      PGE2. Here we show that HIF-1alpha protein significantly accumulated in human
      breast cancer MDA-MB-231 cells in response to the pro-inflammatory cytokine IL
      1beta, but not in COX-2-silenced MDA-MB-231 cells. In contrast HIF-1alpha
      expression could be detected in COX-2- silenced cells in response to the hypoxia
      mimetic agent CoCl(2) and hypoxia. Gene expression profiling in COX-2-containing
      and COX-2-silenced cells showed that the hypoxia-induced transcriptional response
      is largely unaffected by COX-2 silencing. These data suggest that the profound
      effects of COX-2 silencing on inhibiting invasion, tumor growth and metastasis
      from MDA-MB-231 cells are dependent on the induction of IL-1beta-dependent COX-2
      and HIF-1alpha but are independent of hypoxia

PMID- 19390243
TI  - Alterations of mitochondrial function in sepsis and critical illness.
AB  - PURPOSE OF REVIEW: Septic shock is the consequence of a conflict between a
      pathogenic agent and the immune system of the host. This conflict induces an
      immune-mediated cytokine storm, with a whole-body inflammatory response often
      leading to multiple organ failure. Although extensively studied, the
      pathophysiology of sepsis-associated multiorgan failure remains unknown. One
      postulated mechanism is changes in mitochondrial function with an inhibition of
      mitochondrial respiratory chain and a decrease of oxygen utilization. RECENT
      FINDINGS: Mitochondrion is a key organelle in supplying energy to the cell
      according to its metabolic need. Hypoxia and a number of the mediators implicated
      in sepsis and in the associated systemic inflammatory response have been
      demonstrated to directly impair mitochondrial function. A large body of evidence
      supports a key role of the peroxynitrite, which can react with most of the
      components of the electron transport chain, in the mitochondrial dysfunction.
      SUMMARY: A pivotal role is suggested for mitochondrial dysfunction during the
      occurrence of multiorgan failure. Understanding the precise effect of sepsis on
      the mitochondrial function and the involvement of mitochondria in the development
      of multiple organ failure is fundamental. More human studies are thus necessary
      to clarify the mitochondrial dysfunction in the various phases of sepsis (early
      and late phase) before testing therapeutic strategies targeting mitochondria.

PMID- 19390244
TI  - Link between coagulation abnormalities and microcirculatory dysfunction in
      critically ill patients.
AB  - PURPOSE OF REVIEW: The current review discusses the role of coagulation in
      microcirculatory abnormalities and whether anticoagulants may improve
      microvascular perfusion. RECENT FINDINGS: Microvascular alterations frequently
      occur in sepsis and ischemia-reperfusion injury. These alterations are due to
      endothelial dysfunction and interaction of endothelium and circulating cells.
      Although the activation of coagulation has been extensively shown to occur in
      these conditions, microthrombosis seems not to be a predominant factor.
      Nevertheless, the interplay between coagulation, inflammation and the endothelium
      seems to favor microvascular dysfunction. Several agents with anticoagulant
      properties, especially activated protein C and antithrombin, improve the diseased
      microcirculation, but these agents have pleiotropic effects, and it seems
      unlikely that these beneficial effects are linked to direct inhibition of
      coagulation. Current evidence does not support the use of pure anticoagulant
      agents to improve microvascular perfusion. SUMMARY: The activation of coagulation
      may play an indirect role in microvascular dysfunction, through interplay with
      endothelium and inflammation.

PMID- 19390245
TI  - Applying gases for microcirculatory and cellular oxygenation in sepsis: effects
      of nitric oxide, carbon monoxide, and hydrogen sulfide.
AB  - PURPOSE OF REVIEW: Nitric oxide, carbon monoxide, and hydrogen sulfide (H2S) are
      gases that have received attention as signaling molecules regulating many
      biological processes. All of them were reported to have beneficial effects in
      inflammatory states, in particular for microcirculatory perfusion and tissue
      energy balance. Thus, this review will highlight the most important results with
      a focus on resuscitated, clinically relevant experimental models and, if
      available, human studies. RECENT FINDINGS: There is ample evidence that nitric
      oxide, carbon monoxide, and H2S may exert cytoprotective effects in shock states
      due to their vasomotor, antioxidant, and anti-inflammatory properties as well as
      their potential to induce a hibernation-like metabolic state called 'suspended
      animation' resulting from inhibition of cytochrome-c-oxidase. It must be
      emphasized, however, that the three molecules may also be cytotoxic, not only
      because of their inhibition of cellular respiration but also because of their
      marked pro-inflammatory effects. SUMMARY: It is still a matter of debate whether
      manipulating nitric oxide, carbon monoxide, or H2S tissue concentrations, either
      by using the inhaled gas itself or by administering donor molecules or inhibitors
      of their endogenous production, is a useful therapeutic approach to improve
      microcirculatory blood flow, tissue oxygenation, and cellular respiration. This
      is mainly due to their 'friend and foe character' documented in various
      experimental models, but also to the paucity of data from long-term, resuscitated
      large animal experiments that fulfil the criteria of clinically relevant models.

PMID- 19390246
TI  - Healthcare safety committee in Japan: mandatory accountability reporting system
      and punishment.
AB  - PURPOSE OF REVIEW: The publication of To Err is Human by the Institute of
      Medicine highlighted the increased international concern about patient safety.
      Each country has developed its own medical adverse event reporting system. In
      2007, the Japanese government attempted to establish a new accountability system
      in medicine, after an obstetrician was arrested for manslaughter. This paper
      reviews how this accountability system affected Japanese physicians' behavior,
      and describes different types of medical adverse event reporting systems. RECENT
      FINDINGS: In general, reporting of adverse event systems can be either mandatory
      or voluntary, with the purpose being either for learning or for accountability.
      The goal of a newly proposed mandatory accountability system from the Japanese
      government was to investigate the cause of death in medical cases in order to
      clarify liability. Reports generated by this system could potentially be cited in
      civil law suits, administrative sanctions, and criminal prosecutions. After
      announcement of this new system, Japanese physicians began to act defensively,
      fearing criminal prosecution. Refusing to see high-risk patients and 'bouncing'
      (sometimes referred to as 'turfing' or 'dumping') to other hospitals became
      national phenomena. In addition, medical school graduates began avoiding highly
      legally vulnerable specialties. Even though this new system is not yet legalized
      in Japan, at least 153 obstetrics hospitals and 3320 clinics have closed.
      SUMMARY: The new system of investigating medical adverse events in Japan allows
      for incident reports to be utilized in court. This has led to widespread fear of
      prosecution and defensive medicine. The lessons from Japan should be considered
      when other countries implement nationwide accountability systems.

PMID- 19390248
TI  - Can anesthesia information management systems improve quality in the surgical
      suite?
AB  - PURPOSE OF REVIEW: To summarize developments related to the use of anesthesia
      information management systems (AIMS) and quality assurance and quality
      improvement. RECENT FINDINGS: A real challenge for AIMS is that the technology is
      too often seen as a solution. The reality is that the technology is simply a
      tool, which is increasingly being installed by hospitals to give
      anesthesiologists better capabilities for managing quality assurance programs,
      developing guidelines, facilitating computerized decision support, and
      standardizing care in the surgical suite so that every patient receives optimal
      care. Anesthesia groups will likely have to assign a dedicated biomedical team
      and programmer to fully realize the clinical and business benefits of AIMS.
      SUMMARY: Implementation of information technologies in anesthesia as well as in
      all aspects of healthcare redesigns how patients receive care. AIMS accurately
      measure, store, query, and recall vital sign data, and enable the systematic
      analysis of anesthesia-related perioperative data. Using AIMS, quality management
      programs will be able to study more incidents and analyze them more quickly.
      Ideally, decision-support systems with practice guidelines delivered via AIMS
      should help overcome the usual barriers to guideline adherence, and improve care
      and safety.

PMID- 19390247
TI  - Improving safety in the operating room: a systematic literature review of
      retained surgical sponges.
AB  - PURPOSE OF REVIEW: Gossypibomas are surgical sponges that are unintentionally
      left inside a patient during a surgical procedure. To improve this patient safety
      indicator, anesthesiologists will need to work with operating room personnel.
      This study's goal was to systematically review the literature on retained sponges
      to identify body location, time to discovery, methods for detection, and risk
      factors. RECENT FINDINGS: Two hundred and fifty-four gossypiboma cases (147
      reports from the period 1963-2008) were identified via the National Library of
      Medicine's Medline and the Cochrane Library. Gossypibomas (mean patient age 49
      years, range 6-92 years) were most commonly found in the abdomen (56%), pelvis
      (18%), and thorax (11%). Average discovery time equaled 6.9 years (SD 10.2 years)
      with a median (quartiles) of 2.2 years (0.3-8.4 years). The most common detection
      methods were computed tomography (61%), radiography (35%), and ultrasound (34%).
      Pain/irritation (42%), palpable mass (27%), and fever (12%) were the leading
      signs and symptoms, but 6% of cases were asymptomatic. Complications included
      adhesion (31%), abscess (24%), and fistula (20%). Risk factors were case specific
      (e.g. emergency) or related to the surgical environment (e.g. poor
      communication). Most gossypibomas occurred when the sponge count was falsely
      pronounced correct at the end of surgery. SUMMARY: More is being discovered about
      the patterns leading to a retained sponge. Multidisciplinary approaches and new
      technologies may help reduce this low frequency but clinically significant event.
      However, given the complexity of surgical care, eliminating retained sponges may
      prove elusive.

PMID- 19390249
TI  - Managing quality in an anesthesia department.
AB  - PURPOSE OF REVIEW: To provide a practical approach to measure and then improve
      the quality of an academic anesthesia department. RECENT FINDINGS: The quality of
      any entity is defined by the user. Anesthesia departments should adopt practices
      that meet their specific operational needs. The relative importance of each of
      the user groups will be determined by the purpose of an individual department.
      Four categories of users will be considered: patients, surgeons (and other
      proceduralists), the hospital organization and the department itself (i.e.
      faculty and trainees). Patients value avoiding nausea and vomiting and pain after
      surgery, surgeons want cases to start on time with low turnover times, and the
      hospital desires high throughput of surgical cases, all facilitated by department
      faculty who value professional development. Quality improvement efforts in
      anesthesia should be aligned with broad healthcare quality improvement
      initiatives and avoid distortions in perceptions of quality by over-emphasizing
      what is easily measurable at the expense of what is important. SUMMARY:
      Departments of anesthesia should develop performance criteria in multiple domains
      and recognize the importance of human relationships (between staff and between
      staff and patients) in quality and safety. To improve the value of anesthesia
      services, departments should identify their user groups, survey them to determine
      what attributes are important to the user, then deliver, measure, monitor and
      improve them on an ongoing basis.

PMID- 19390250
TI  - Economics and outcome in the intensive care unit.
AB  - PURPOSE OF REVIEW: Medical care costs represent a large proportion of the gross
      domestic product in developed countries, and intensive care units (ICUs) consume
      a significant amount of those resources. The aim of this review is to analyze how
      the healthcare cost problem is studied in critically ill patients. RECENT
      FINDINGS: Permanent staffing and other overhead costs have the greatest impact on
      ICU costs. A growing number of studies from around the world are quantifying the
      costs of ICU care. Mechanical ventilation, particularly in severely ill patients,
      and sepsis management are responsible for much of the economic burden in the ICU.
      New expensive therapies and life support systems make formal economic analyses
      necessary. SUMMARY: Although economic justification should not be the only issue
      to influence treatments offered in the ICU, increasing use of tools such as cost
      benefit analyses is needed to help with medical decisions on the critically ill
      patient.

PMID- 19390251
TI  - Quality assessment by external bodies: intended and unintended impact on
      healthcare delivery.
AB  - PURPOSE OF REVIEW: External quality assessment programs in the form of pay for
      performance, report cards and national rankings are rapidly overtaking more
      traditional, internal quality assessment efforts and external clinical practice
      guidelines. Although such initiatives are designed to improve healthcare quality
      by promoting competition and increasing transparency, review of their efficacy
      and unintended effects is just coming to the national spotlight. RECENT FINDINGS:
      Critical evaluation of external quality assessment programs remains limited
      despite their scope, speed and breadth of implementation. Recent publications,
      however, suggest that external quality assessment efforts may have major
      unintended consequences. These include effects on patient decision-making, the
      'dynamic equilibrium' of patient care, healthcare disparities, medical innovation
      and practice patterns. SUMMARY: In their early years of implementation, external
      quality assessment programs have already had significant consequences in the
      healthcare system. As new tools become available, their full impact on care and
      caregivers must be thoroughly evaluated. Careful consideration of clinical
      practice implications and an understanding of the risks are critical before
      accepting and implementing new assessment paradigms. The substantial and
      widespread effects of these programs should prompt further evaluation from the
      medical community.

PMID- 19390252
TI  - Coagulopathy in trauma patients: importance of thrombocyte function?
AB  - PURPOSE OF REVIEW: Trauma-induced coagulopathy results from a complex interplay
      between shock resuscitation and impaired clotting protease function. A
      pathophysiological role of platelets in this condition remains as yet undefined.
      This review examines our current knowledge of platelet function in haemostasis,
      possible mechanisms for aberrant activity in trauma and the role of platelet
      transfusions in exsanguinating haemorrhage. RECENT FINDINGS: Platelet adhesion
      and aggregation enable a haemostatic plug to form at the site of vessel injury.
      As described within cell-based models of thrombin generation, platelet membranes
      provide a platform to amplify clot formation. There is evidence to suggest
      platelet activity may be of greater importance than platelet number for clot
      integrity. Analysis of platelet function is limited by currently available
      devices. Therefore, the precise role and triggers for platelet transfusion in
      trauma have yet to be fully characterized. Retrospective studies show that early
      high-volume platelet transfusion in trauma may be associated with similar outcome
      benefits observed in high ratio plasma: red blood cell replacement. SUMMARY:
      Platelets undoubtedly play a pivotal role in haemostasis and trauma-induced
      coagulopathy. However, their specific dysfunction in trauma remains to be
      elucidated. Further research to characterize the dysfunctional pathways of the
      platelet response is required, together with clinical trials of the optimal
      timing and dose of platelet transfusions.

PMID- 19390253
TI  - Time for changing coagulation management in trauma-related massive bleeding.
AB  - PURPOSE OF REVIEW: New insights into the pathophysiology of trauma-induced
      coagulopathy, the increasing availability of point-of-care devices and awareness
      of side effects of intravenous fluids and traditional fresh frozen plasma therapy
      has encouraged new concepts for managing massive blood loss. RECENT FINDINGS:
      Trauma-induced coagulopathy primarily results from blood loss, hypovolemia
      induced activation of the protein C system and consequent increase of the
      fibrinolytic potential, whereas hemodilution, localized consumption of clotting
      factors and platelets, hypothermia, acidosis, anemia and hypocalcemia further
      decrease the hemostatic potential. The widespread use of viscoelastic devices
      highlighted the importance of the contribution of fibrinogen to clot firmness, a
      precondition for cessation of bleeding. The evidence is growing that targeted
      therapy using coagulation factor concentrates guided by viscoelastic measurements
      enables effective correction of severe coagulopathy. SUMMARY: During massive
      blood loss, viscoelastic measurements should guide aggressive treatment of
      deficiency or hyperfibrinolysis or both. In addition, the impact of contributing
      factors should be considered and as far as possible corrected. New data
      underscore the importance of avoiding hypoperfusion, and the use of coagulation
      factor concentrates should enable more effective correction of coagulopathy.

PMID- 19390254
TI  - Role of storage time of red blood cells on microcirculation and tissue
      oxygenation in critically ill patients.
AB  - PURPOSE OF REVIEW: To review the current literature on the role of storage time
      of transfused red blood cells on microcirculation and tissue oxygenation in
      critically ill patients. RECENT FINDINGS: The actual target of transfusion of red
      blood cells is the maintenance of adequate tissue oxygenation. Recent studies
      suggest that, besides hemoglobin concentration, mixed or central venous oxygen
      saturation may also be used as surrogate markers for the estimation of
      transfusion requirement. However, variables reflecting the concrete target of
      transfusion, that is tissue oxygenation, appear to be more suitable in this
      regard. In addition, there is an increasing body of evidence on adverse effects
      of transfusion of--primarily older--red blood cells on tissue oxygenation and
      microcirculation. This might be explained, at least in part, by so-called storage
      lesions, which commence immediately after donation of blood and aggravate over
      time. SUMMARY: Large-scale prospective randomized trials are needed to explicitly
      clarify the role of new transfusion triggers, such as tissue oxygenation, and the
      impact of storage lesions of packed red blood cells on tissue oxygenation and-
      more important--on clinical outcomes in different patient populations.

PMID- 19390255
TI  - The role of thromboelastometry and recombinant factor VIIa in trauma.
AB  - PURPOSE OF REVIEW: Recombinant factor VIIa (rFVIIa) and thromboelastography have
      acquired increasing importance in patients with severe bleeding and coagulopathy.
      This article reviews the current opinions regarding their use, with the purpose
      of clarifying the ambiguities that exist in dealing with trauma patients. RECENT
      FINDINGS: Recent evidence encourages the early use of rFVIIa and
      thromboelastography in the severe trauma patient with hemorrhagic shock, as a
      component of the damage control strategy. rFVIIa may decrease short-term
      mortality and the rate of required blood components during resuscitation, with no
      apparent increase in thromboembolic complications. Thromboelastometry enables
      better and earlier recognition of the coagulopathy accompanying such trauma
      patients. In patients with traumatic brain injury and coagulopathy, rFVIIa may
      delay or even halt the need for surgery, with no proven decrease in mortality. In
      those who needed urgent neurosurgical intervention, rFVIIa may rapidly correct
      the coagulopathy, enabling earlier and safer surgical intervention. SUMMARY:
      Thromboelastometry may guide the medical staff when and to whom rFVIIa could be
      administered. Evidence also encourages the use of rFVIIa in traumatic brain
      injury. More research is required to prove decreases in mortality using both
      thromboelastography and rFVIIa in trauma, with a focus on clear end points and
      goal-directed therapy.

PMID- 19390256
TI  - Transfusion strategies in postinjury coagulopathy.
AB  - PURPOSE OF REVIEW: Coagulopathy represents one of the major challenges in the
      management of the severely injured patient. The present review will attempt to
      define the current 'optimal' transfusion strategies for the coagulopathic trauma
      patient and to assess potential weaknesses in the pertinent literature. RECENT
      FINDINGS: Existing limitations in the management of postinjury coagulopathy
      include the lack of a uniform definition of the entity, the lack of understanding
      the mechanisms, and the lack of accurate and rapid diagnostic tests. Rapid
      thromboelastography represents an improved diagnostic modality that allows 'point
      of-care' testing of postinjury coagulopathy and monitoring of transfusion
      strategies. Ongoing controversies in the field include the optimal target blood
      pressure and the ideal threshold for blood component transfusions in the
      hospital. Furthermore, the concentration of plasma transfusions remains an
      ongoing debate. SUMMARY: Coagulopathy has a significant impact on survival after
      major trauma. Most recent publications in the field are of retrospective design,
      and thus do not allow definitive recommendations for clinical practice. Well
      designed prospective trials and improved basic research studies are required to
      improve this important aspect of trauma care.

PMID- 19390258
TI  - Abdominal paracentesis and thoracocentesis.
AB  - Abdominal paracentesis and thoracocentesis are common bedside procedures with
      diagnostic, therapeutic and palliative roles. We describe a useful and familiar a
      useful and familiar technique with the use of a multiple lumen catheter commonly
      used for central venous line insertion for drainage of ascites or moderate to
      large pleural effusions. The use of a multiple lumen catheter allows easier and
      more rapid aspiration of fluid with a smaller probability of the side holes being
      blocked as compared to the standard needle or single catheter methods. This is
      particularly useful in situations where the dedicated commercial kits for
      thoracocentesis and abdominal paracentesis are not readily available.

PMID- 19390257
TI  - Transfusion in trauma: why and how should we change our current practice?
AB  - PURPOSE OF REVIEW: Major trauma is often associated with hemorrhage and
      transfusion of blood and blood products, which are all associated with adverse
      clinical outcome. The aim of this review is to emphasize why bleeding and
      coagulation has to be monitored closely in trauma patients and to discuss the
      rationale behind modern and future transfusion strategies. RECENT FINDINGS:
      Hemorrhage is a major cause of early death after trauma. Apart from the initial
      injuries, hemorrhage is significantly promoted by coagulopathy. Early
      identification of the underlying cause of hemorrhage with coagulation tests
      (routine and bedside) in conjunction with blood gas analysis allow early goal
      directed treatment of coagulation disorders and anemia, thereby stopping bleeding
      and reducing transfusion requirements. These treatment options have to be adapted
      to the civilian and noncivilian sector. Transfusion of blood and its components
      is critical in the management of trauma hemorrhage, but is per se associated with
      adverse outcome. Decisions must weigh the potential benefits and harms. SUMMARY:
      Future transfusion strategies are based on early and continuous assessment of the
      bleeding and coagulation status of trauma patients. This allows specific and goal
      directed treatment, thereby optimizing the patient's coagulation status early,
      minimizing the patient's exposure to blood products, reducing costs and improving
      the patient's outcome.

PMID- 19390259
TI  - Laparoscopic T-tube placement after common bile duct exploration: a simple
      technique.
AB  - INTRODUCTION: Laparoscopic T-tube insertion into common bile duct (CBD) can be
      technically challenging. We describe a technique to facilitate CBD T-tube
      placement. METHOD: The T-limb was cut to appropriate size and guttered along one
      third of its circumference lengthwise. One end of T-limb was secured to the long
      stem using a tie. The free end was introduced into the abdomen through the
      epigastric port. Using nontraumatic graspers, this free end was advanced into the
      CBD. Once the whole of T-limb was inside, the tie was cut, and the T-tube would
      spring into place. Choledochotomy was sutured snugly around the T-tube. The long
      limb was taken out through the lateral port of the abdominal wall. RESULTS: There
      was no dislodgment or removal difficulty in all cases. This manoeuvre required <1
      minute. CONCLUSIONS: This technique allows reliable and easier T-tube placement
      into CBD, requiring no ancillary devices. It shortens the steep learning curve.
      SYNOPSIS: Laparoscopic placement of T-tube in CBD can be safely and easily
      manipulated in the described technique.

PMID- 19390260
TI  - Laparoscopic en bloc resection of locally advanced colon cancer with involvement
      of the liver, small bowel, omentum, and abdominal wall.
AB  - BACKGROUND: Locally advanced colon cancer with the involvement of adjacent organs
      is treated radically with en bloc resection with negative margins. Laparoscopy is
      seldom recommended for such patients. METHODS: Operative laparoscopic technique
      is presented for radical en bloc resection of locally advanced right colon
      cancer. RESULTS: The patient is a 56-year-old morbidly obese (body mass index 47)
      male, who was scheduled to undergo a routine laparoscopic right hemicolectomy and
      at exploration was found to have a large mass involving segments V and VI of the
      liver, small bowel, omentum, and abdominal wall. A laparoscopic-assisted en bloc
      resection was performed. The patient went home in 7 days. The tumor was staged as
      T4N0M0, American Joint Commission on Cancer stage IIb with 21 negative nodes.
      CONCLUSIONS: Laparoscopic resection for selected patients with locally advanced
      colonic neoplasms should be considered an option in tertiary referral centers.

PMID- 19390261
TI  - Pelvic cancer recurrence: drop the arrow in the target.
AB  - BACKGROUND: Local recurrence of pelvic cancer is a therapeutic challenge. Medical
      history retrieve frequently high dose radiotherapy and multiple pelvic surgery.
      Thus, surgical resection is complex and leads to hazardous postoperative courses.
      We report a case of radiofrequency thermoablation (RFTA) of an isolated pelvic
      recurrence. CASE: A 53-year-old woman presented in 2006 with a small (20 mm)
      pelvic recurrence of an anal canal cancer initially treated by radiochemotherapy
      and amputation of the rectum. The recurrence was localized in the left vaginal
      wall, involving the obturator internus muscle. Treatment consisted on primary
      chemotherapy followed by RFTA under real time endovaginal sonography with cooling
      of the bladder. Small vaginal wall necrosis occurred in postoperative courses and
      rapidly cicatrized. The patient was still alive without evolution 22 months after
      the treatment. CONCLUSIONS: RFTA is a feasible therapeutic option for some
      selected small isolated pelvic cancer recurrence. It allows good local control
      with survival improvement.

PMID- 19390262
TI  - Replacement of a feeding tube through the gastric tube in patients after
      esophagectomy with retrosternal reconstruction.
AB  - INTRODUCTION: We present our technique of endoscopic replacement of the
      jejunostomy through the stomach conduit in patients after esophagectomy with
      retrosternal reconstruction. METHODS: After an upper gastrointestinal tract
      endoscopy was performed, the stomach conduit was sufficiently inflated with air
      and the site of the previously removed gastric tube was confirmed by the puncture
      using 23 G needle. After an approximately 6-mm incision was made under local
      anesthesia, a 4-mm peel-off introducer sheath was advanced into the stomach
      conduit under endoscopic control. A 3-mm jejunostomy tube was inserted through
      the sheath and placed into the jejunum using the endoscopic guidance. Using
      endoscopy, the jejunostomy tube was confirmed to be placed without bending.
      RESULTS: Between 1998 and 2006, subtotal esophagectomy with retrosternal cervical
      esophagogastrostomy was performed in 48 patients. All patients were inserted with
      at least either jejunostomy tube or decompression tube through the stomach
      conduit. Among them, 11 patients (23%) were performed percutaneous replacement
      jejunostomy through the stomach conduit. There were 9 men and 2 women whose mean
      age was 67 years (range: 59 to 76 y). Replacement of the jejunostomy tube was
      successful in all patients. The procedure required about 30 minutes. There were
      no deaths and no procedural complications. After 24 hours, the tube was used for
      enteral feeding. No late complication occurred in our cases. CONCLUSIONS: We
      believe that the endoscopic percutaneous approach described in this report is
      safe and effective in patients after esophagectomy with retrosternal
      reconstruction.

PMID- 19390263
TI  - Transperitoneal laparoscopic surgery using endostaplers for adult unilateral
      diaphragmatic eventration.
AB  - A 27-year-old woman was referred owing to elevation of the left diaphragm on a
      chest roentgenogram. Preoperative examinations revealed neither herniation nor
      incarceration of the digestive tracts into the thoracic cavity. A diagnosis of
      unilateral diaphragmatic eventration was made, and laparoscopic surgery was
      performed. Intraoperative findings revealed a partially thin diaphragm.
      Immediately after careful opening of the thoracic cavity, respiration was
      switched to selective right lung ventilation. The extended thin diaphragm was
      easily gripped. The whole layer of the diaphragm, including a pleural hole, was
      resected using an endostapler without involving the lung tissue at the normal
      thick diaphragm. This endostapling procedure was repeated until the desired
      tension was obtained, and a chest tube was then inserted. X-ray fluorographic
      views showed a functioning repaired diaphragm. The postoperative course was
      uneventful with normalization of the diaphragm. In this paper, we present our
      modified techniques of transperitoneal minimally invasive surgery for
      diaphragmatic eventration.

PMID- 19390264
TI  - Mesh erosion as a complication of laparoscopic fundoplication with prosthetic
      hiatal closure: report of a case.
AB  - BACKGROUND: Laparoscopic fundoplication has become the standard procedure for
      surgical management of gastroesophageal reflux disease. Simple cruroplasty is
      associated with a high recurrence rate and most authors recommend the use of
      prosthetic meshes for crural closure. METHODS: Herein we report a patient who was
      admitted with the complaint of severe dysphagia a year after laparoscopic
      fundoplication with prosthetic hiatal closure. RESULTS: The patient presented
      with mesh erosion into the esophagus and required a distal esophageal resection.
      CONCLUSIONS: This case demonstrates that appropriate surgical technique is
      important for preventing mesh-related complications. A small-sized mesh should be
      placed so as to have no contact with the esophagus and should be secured
      sufficiently to the diaphragmatic crura to avoid the potential complications of
      mesh reinforcement.

PMID- 19390265
TI  - Injury of the thoracic aorta during laparoscopic esophagectomy.
AB  - We report an unusual complication of laparoscopic esophagectomy for carcinoma.
      During posterior transhiatal dissection, massive bleeding occurred from the left
      side of the supradiaphragmatic thoracic aorta. A small tear was clearly visible
      and temporary bleeding control by packing and pressure with a grasper through one
      of the trocars was effective. A median laparotomy was performed and the aorta was
      sutured using a standard laparoscopic needle holder. The esophagectomy was
      successfully completed through a right thoracic approach. Injury to the
      intrathoracic aorta may occur during transhiatal dissection of the lower
      mediastinum. Use of a laparoscopic needle holder allowed to repair the
      supradiaphragmatic aorta through a laparotomy without the need of patient
      repositioning for a transthoracic approach.

PMID- 19390266
TI  - Laparoscopy-assisted completion total gastrectomy for gastric cancer in remnant
      stomach: report of 2 cases.
AB  - The completion total gastrectomy is often performed in gastric cancer patients
      who have previously undergone distal gastrectomy owing to benign or malignant
      disease. This procedure includes not only removal of the remnant stomach, but
      also a lymphadenectomy in accordance with upper third gastric cancer. Although
      laparoscopy-assisted gastrectomy has been approved as one of the treatments of
      choice for early gastric cancer and its application has also been extend to
      advanced gastric cancer, only a few studies have reported on laparoscopy-assisted
      completion total gastrectomy. This is probably because the procedure is
      technically complicated procedure due to the intra-abdominal adhesion and
      anatomical changes. Recently, we successfully carried out laparoscopy-assisted
      completion total gastrectomy in 2 patients diagnosed with advanced gastric
      cancers in the remnant stomach. Distal gastrectomy was initially performed using
      laparoscopy-assisted and open procedures, respectively. Furthermore, we conducted
      the curative operations through a sufficiently extended lymphadenectomy or even
      through the resection of surrounding organs.

PMID- 19390267
TI  - Needloscopy-assisted transvaginal cholecystectomy.
AB  - The reasons for hybrid surgery are various: endoscopic peritoneoscopy under
      laparoscopic visualization provides a safe way to improve pure natural orifice
      endoscopic surgery with less abdominal incision. Herein we are presenting a
      hybrid technique composed of advantages of needloscopy and natural orifice
      transluminal endoscopic surgery (NOTES). Two women with symptomatic
      cholelithiasis have undergone successful needloscopy-assisted transvaginal
      cholecystectomies. Main principle of this approach is the ability of performing
      cholecystectomy procedure same as in standard laparoscopic cholecystectomy. In
      contrast, we get benefit of less abdominal trauma due to transvaginal endoscopic
      exposure, clipping maneuver, and removal of gallbladder. We believe that, trend
      of more minimal invasive surgery which created the idea of NOTES, gets benefit
      from hybrid techniques as an interval step toward NOTES when waiting for the
      ideal equipment and sufficient experience.

PMID- 19390268
TI  - Volvulus of the sigmoid colon treated by percutaneous endoscopic colostomy.
AB  - Volvulus of the sigmoid colon is a condition that, in the Western world,
      predominately affects the elderly. In fit patients sigmoid colectomy, after a
      period of decompression, is the treatment of choice. However, this carries a high
      mortality in elderly high-risk patients. Percutaneous endoscopic colostomy (PEC)
      has been reported as a treatment for those who are considered high risk for
      surgery. We report the successful use of PEC in an 87-year-old lady, for the
      treatment of recurrent sigmoid volvulus, without complication. This procedure has
      also been used effectively for colonic pseudo-obstruction, constipation, and
      obstructed defecation. There are various complications associated with PEC, the
      most serious of which is tube migration and fecal peritonitis. Our experience
      supports the use of PEC to treat sigmoid volvulus in those too frail for colonic
      resection.

PMID- 19390269
TI  - Laparoscopic splenic artery aneurysm resection: review of current trends in
      management.
AB  - Splenic artery aneurysm, although rare, is the commonest visceral aneurysm. Its
      management options have expanded with advances in minimally invasive techniques.
      In the last decade, the laparoscopic technique has gained popularity owing to its
      simplicity, safety, and short postoperative course in the experienced hand. We
      recommend the laparoscopic approach to be considered as the first option in the
      management of splenic artery aneurysm. It is of particular use in pregnant women
      where this condition has a high mortality and morbidity.

PMID- 19390270
TI  - Gastric applications of electrical field stimulation.
AB  - Advances in clinical applications of electricity have been vast since the launch
      of Hayman's first cardiac pacemaker more than 70 years ago. Gastric electrical
      stimulation devices have been recently licensed for treatment of gastroparesis
      and preliminary studies examining their potential for use in refractory obesity
      yield promising results.

PMID- 19390271
TI  - Postlaparoscopic iatrogenic pseudoaneurysms of the arteries of the peritoneal and
      retroperitoneal space: case report and review of the literature.
AB  - BACKGROUND AND AIMS: Laparoscopic surgery procedures are associated with a low
      percentage of cases of iatrogenic traumatic laceration of the arteries of the
      peritoneal and retroperitoneal space. These lesions rarely lead to pseudoaneurysm
      formation. In 1 case, we performed a meta-analytic review of the literature on
      postlaparoscopic iatrogenic pseudoaneurysms focusing on specific parameters: (1)
      artery involved, (2) type of laparoscopic operation, (3) time interval between
      the laparoscopic operation and the final diagnosis of the pseudoaneurysm, (4)
      clinical presentation, (5) diagnostic tools used, (6) mode of treatment applied,
      and (7) clinical outcome. MATERIALS AND METHODS: We searched Medline for
      pseudoaneurysms developing as complications of laparoscopic procedures. The
      search terms used were "iatrogenic pseudoaneurysm," "complications after
      laparoscopic procedures," "traumatic arterial laceration," "pseudoaneurysm
      formation," and "postoperative hematoma" in various combinations. RESULTS AND
      CONCLUSIONS: A total of 66 cases were retrieved. Postlaparoscopic iatrogenic
      pseudoaneurysms are late manifestations of arterial complications developing
      during routine laparoscopy. There are 66 reported cases of this type of
      complication in the literature. The majority occurs in the arteries of the
      operation field of the respective laparoscopic procedure. Distal vessels are
      involved less frequently. They usually present after a mean period of
      approximately 6 weeks. The hepatic and renal arteries are usually affected. The
      clinical picture includes upper and lower gastrointestinal bleeding, diffuse or
      localized abdominal pain, hematuria, and drain bleeding.

PMID- 19390272
TI  - Preoperative dilatation does not affect the surgical outcome of laparoscopic
      Heller myotomy and Dor fundoplication for esophageal achalasia.
AB  - BACKGROUND: Laparoscopic Heller myotomy and Dor fundoplication are now widely
      performed for achalasia. In patients who have had dilatation in the past,
      inflammation between the esophageal mucosal and muscular layers may make it
      difficult to perform myotomy. PURPOSE: We investigated the effects of
      preoperative dilatation on the surgical outcomes. METHOD: : One hundred and
      twelve patients were divided into 2 groups: 37 patients with a past history of
      preoperative dilatation and 75 patients who had no history of preoperative
      dilatation. The operating time, intraoperative blood loss, days required to
      resume postoperative oral intake, postoperative hospital stay, improvement in
      dysphagia, and incidence of postoperative esophagitis were compared. RESULTS: The
      operating time, intraoperative blood loss, postoperative hospital stay, and
      improvement of dysphagia were no significant differences between these groups.
      Furthermore, there were no significant differences in the incidence of
      postoperative esophagitis. CONCLUSIONS: The therapeutic outcome of laparoscopic
      Heller myotomy and Dor fundoplication is not affected by preoperative pneumatic
      dilatation.

PMID- 19390273
TI  - Laparoscopic cholecystectomy in patients undergoing continuous ambulatory
      peritoneal dialysis: a case-control study.
AB  - This case-control study assesses laparoscopic cholecystectomy (LC) in patients
      with end-stage renal disease treated with continuous ambulatory peritoneal
      dialysis. Eleven patients receiving peritoneal dialysis treatment and 33 patients
      without end-stage renal disease who had undergone an elective LC were compared.
      Medical records were reviewed, and laboratory values and outcomes and results
      were analyzed. The peritoneal dialysis group showed a higher frequency of
      associated disease and previous abdominal surgery; a lower hemoglobin and
      platelet count; and elevated alkaline phosphatase, blood urea nitrogen, and
      creatinine values. Statistically significant between-group differences were found
      with regard to postoperative complications and postoperative hospital stay days.
      One procedure in each group was converted to an open cholecystectomy. No patient
      in the peritoneal dialysis group who underwent a LC had peritonitis. No other
      catheter-related complications occurred. LC may be performed with low
      complication rates in patients undergoing continuous ambulatory peritoneal
      dialysis with an experienced team.

PMID- 19390274
TI  - Percutaneous transhepatic lithotripsy with the holmium: YAG laser for the
      treatment of refractory biliary lithiasis.
AB  - Fourteen patients who failed at least 1 endoscopic retrograde
      cholangiopancreatograpy attempt underwent Holmium laser biliary lithotripsy
      between 2003 and 2007. Ten had prior biliary surgeries, 7 harbored multiple
      stones, and 6 had common bile duct strictures. Mean age at surgery was 63.6 years
      (50 to 80 y), biggest stone burden 30 mm, mean operative time 58.4 minutes (24 to
      105), and stone free rate 85.7%. One patient had postoperative bleeding from the
      choledochostomy tube that eventually resolved spontaneously and 3 patients had
      postoperative cholangitis managed conservatively. Neither conversions to open
      surgery nor mortality was recorded. Two patients were diagnosed with
      cholangiocarcinoma missed by previous endoscopic retrograde
      cholangiopancreatograpy. After a mean follow-up of 18.9 months (2 to 43) no de
      novo strictures were recorded. Percutaneous choledochoscopy with holmium laser
      lithotripsy is a safe and effective minimally invasive technique to treat complex
      biliary stone disease and may preclude high-risk open biliary tract surgery.

PMID- 19390275
TI  - Pediatric advanced appendicitis: open versus laparoscopic approach.
AB  - PURPOSE: Optimal surgical approach for advanced pediatric appendicectomy remains
      controversial. We compare the open versus the laparoscopic approach. METHODS:
      Retrospective case notes review of children operated on for advanced appendicitis
      between January 2005 and July 2006 was undertaken for length of hospital stay,
      operating time, wound complications, need for further surgery, and hospital
      readmission. RESULTS: Forty children were included, 17 were treated with open
      approach and 23 with laparoscopic approach. There was no conversion from
      laparoscopic to open approach. Overall complication rate, length of hospital
      stay, and need for further surgery were similar in both groups. The mean
      operative time was longer in the laparoscopic group. Wound complications occurred
      more in the open group. Readmission for gastrointestinal obstruction was noted in
      the laparoscopic group. CONCLUSIONS: Laparoscopic approach is safe for advanced
      appendicitis in children. The outcomes are comparable in both study groups.

PMID- 19390276
TI  - Impact of obesity on laparoscopic-assisted left colectomy in different stages of
      the learning curve.
AB  - PURPOSE: This study is aimed at verifying if the surgeon's experience has an
      impact on the risk of conversion to open surgery of laparoscopic left colectomy
      performed in obese patients. METHODS: A multiple logistic regression analysis was
      performed of 181 laparoscopic left hemicolectomies completed between April 2001
      and June 2006. The results were analysed statistically in relation to the
      learning curve, by comparing factors that could have had an impact on the risk of
      conversion in the first 91 cases and in the last 90 cases. RESULTS: The overall
      conversion rate was 11%. Only weight level was found to be predictive of
      conversion to open surgery. No death was observed. Sixteen patients presented
      postoperative complications (8.8%), with no significant differences between obese
      and nonobese patients (P=0.95). The conversion rate was higher in the group of
      the first 91 cases: 15.6% versus 6.6% (P=0.05). Average body mass index of
      converted patients resulted as being higher than that of nonconverted ones
      (29.97+/-3.76 vs. 25.48+/-3.72; P<0.001) during the first period of the learning
      curve, but the difference was not observed during the second period (P=0.87). On
      multiple logistic regression analysis, obesity was found to be predictive of
      conversion only during the first period. CONCLUSIONS: The data indicate that the
      laparoscopic colorectal surgery is feasible and effective in obese patients both
      when the surgeon is expert in laparoscopic colorectal resection and at the
      initial phase of the experience. At the initial phase of the experience obesity
      constitutes a higher risk of conversion to open surgery.

PMID- 19390277
TI  - Laparoscopic versus open proctectomy for rectal cancer: patients' outcome and
      oncologic adequacy.
AB  - BACKGROUND: The aim of this study was to compare laparoscopic management of
      rectal cancer to open surgery. METHODS: The medical records of patients who
      underwent elective laparoscopic or open proctectomy for rectal cancer between
      November 2004 and July 2006 were retrospectively reviewed. RESULTS: Thirty-two
      patients in the laparoscopic group (LG) were matched for tumor location, stage,
      comorbidity, and type of surgical procedure to 50 patients in the open group
      (OG). There were no statistically significant differences between the groups
      relative to American Society of Anesthesiologists score or tumor, node,
      metastasis stage; however, body mass index and age of the LG were significantly
      lower compared with the OG (P<0.05). In the LG, the procedure was successfully
      laparoscopically completed in 28 patients (87.5%). The median operative time was
      240 minutes in the LG and 185 minutes in the OG (P< 0.05). Overall morbidity was
      25% and 38%, respectively (P=0.1), the median hospital stay was 6 days, and
      median time to first bowel movement was 3 days in the LG compared with 7 and 4
      days in the OG, respectively (P=0.7 and 0.01, respectively). The number of
      identified lymph nodes, distal and radial margins were comparable between both
      groups. Median follow-up was 10 (1 to 18) months. CONCLUSIONS: Laparoscopic
      proctectomy for rectal cancer is feasible in 87.5% of patients and despite a
      longer operative time compared with laparotomy, is safe with the advantages of
      faster recovery of bowel function. This procedure does not compromise the
      oncologic adequacy of resection or significantly differ from open proctectomy
      relative to short-term outcomes.

PMID- 19390278
TI  - Lessons learned from the analysis of 200 laparoscopic sigmoid resections for
      diverticulitis.
AB  - INTRODUCTION: Since the beginning of laparoscopic surgery indications for
      laparoscopic colon resections are still discussed controversively. In the latest
      studies benefit for laparoscopic approach is reported. The aim of this study was
      to evaluate the feasibility of laparoscopic sigmoid resections for diverticulitis
      regarding conversion rate, operation time and intraoperative and postoperative
      complications, and defining strategies to prevent complications. METHODS: Out of
      a prospective database with all laparoscopic colon resection between May 1999 and
      January 2008 the patients with laparoscopic sigmoid resection for diverticulitis
      were analyzed. Preoperative diagnosis was made by abdominal computed tomography
      with irrigoscopy and/or endoscopy. Indications for laparoscopic sigmoid
      resections were diverticulitis as an early elective or elective operation and
      selected cases with perforated diverticulitis. RESULTS: Between May 1999 and
      January 2008, 200 patients (97 women, 103 men) were operated by laparoscopy for
      diverticulitis. Mean age at surgery was 59 years (range: 27 to 86); mean
      preoperative body mass index was 27.2 kg/m2 (range: 20 to 38). Mean operating
      time was 121 minutes (range: 60 to 239). Operating time was reduced due to
      experience and dropped from a mean of 150 minutes for the first 50 patients, 115
      minutes for the second, 110 minutes for the third, and 107 minutes for the last
      50 patients (P<0.05). Conversion rate was 1.5%, total morbidity rate was 19%, and
      reoperation rate was 6%. CONCLUSIONS: Laparoscopic sigmoid resections for
      diverticulitis can be performed with great safety and low conversion rate.
      Several adjustments in operation technique and perioperative management had to be
      done to achieve a complication rate and conversion rate at an acceptable low
      level.

PMID- 19390279
TI  - Predictors of recurrence after laparoscopic ventral hernia repair.
AB  - Laparoscopic ventral hernia repair (LVHR) is widely used to manage ventral
      hernias, but predictors of hernia recurrence have been poorly investigated. This
      retrospective study investigated the influence of common risk factors on hernia
      recurrence. Data from 146 consecutive, unselected patients who underwent LVHR
      between 2000 and 2006 were collected. Demographic, clinical, and perioperative
      parameters were analyzed to identify predictable risk factors for hernia
      recurrence. Both univariate and multivariate Cox's regression analysis were
      employed. The overall recurrence rate was 8% (12 patients) after an average
      follow-up of 45 months. On univariate analysis, smoking (P=0.01) and earlier
      repair (P<0.00) were significantly different in recurred patients. However, only
      earlier repair was an independent predictor of multivariate Cox's regression
      analysis (hazard ratio 0.085, 95% confidence interval: 0.020-0.355; P=0.001).
      LVHR is a safe technique to repair ventral hernias. However, smokers with earlier
      failed repair attempts have a higher risk of recurrence.

PMID- 19390280
TI  - Assessment of strangulated content of the spontaneously reduced inguinal hernia
      via hernia sac laparoscopy: preliminary results of a prospective randomized
      study.
AB  - This prospective randomized study aimed to evaluate the impact of hernia sac
      laparoscopy on the morbidity and mortality in cases with a spontaneous reduction
      of the strangulated hernia content before the assessment of its viability. Ninety
      five patients underwent operation owing to incarcerated hernia. Forty-one
      patients, whose strangulated indirect inguinal hernia spontaneously reduced
      before the viability of the content was assessed, were included in this study.
      They were randomly assigned to 2 groups: group A (21 patients managed using
      hernia sac laparoscopy) and group B (20 patients managed without laparoscopy).
      The median hospital stay was 28 hours for group A and 34 hours for group B. Four
      patients of group B had major complications whereas there was none observed in
      the group A. Two unnecessary laparotomies and 2 deaths occurred in group B.
      Hernia sac laparoscopy seems to be an accurate and safe method allowing to
      prevent unnecessary laparotomy and especially in high-risk patients it
      contributes to decrease major morbidity.

PMID- 19390281
TI  - Maternal and fetal near-term sheep cytokine responses to carbon dioxide
      pneumoperitoneum.
AB  - It is known that carbon dioxide (CO2) pneumoperitoneum induces fetal acidosis in
      pregnant ewes. Our aim was to determine changes of the levels of maternal and
      fetal cytokines interleukin-6, interleukin-8, and tumor necrosis factor alpha
      after CO2 pneumoperitoneum in pregnant ewes. Eight ewes with singleton
      pregnancies of 120 to 140 days gestation were anesthetized and intubated.
      Insufflation produced modest but significant maternal arterial hypercapnia (an
      increase of 10.7 mm Hg; P<0.001) and acidosis (a decrease in mean pH of 0.1.04;
      P=0.0005). Fetal pCO2 was increased by 15.3 mm Hg on average and pH was decreased
      by 0.11 U on average immediately after desufflation (both P<0.001). No
      significant difference was observed in the concentration of cytokine in the
      maternal or fetal blood samples. These results suggest that respiratory acidosis
      does not lead to the elevation of cytokines in pregnant ewes and fetuses, which
      may contribute to premature labor.

PMID- 19390282
TI  - Effect of increased abdominal pressure on cytokines (IL1 beta, IL6, TNFalpha), C
      reactive protein (CRP), free radicals (NO, MDA), and histology.
AB  - BACKGROUND: It is generally accepted that proinflammatory mediators, including
      cytokines, are responsible for the metabolic changes associated with injury.
      Recent clinical and experimental studies have also shown that the laparoscopic
      procedures actually produce ischemia-reperfusion injury in the organs by oxygen
      derived free radicals. This study aimed to assess the effect of different
      insufflation pressures and laparotomy on tissue response by comparing the
      proinflammatory cytokines, C-reactive protein, and serum and tissue levels of
      oxygen-derived free radicals. METHODS: Forty mature New Zealand white rabbits
      were assigned to 4 groups of 10 animals. In groups 1 to 3, CO2 pneumoperitoneum
      was created using an automatic insufflator to the designated pressure of 10, 15,
      and 20 mm Hg, respectively. The remaining 10 animals underwent laparotomy using
      10 cm midline incision (group 4). Blood samples were collected before (0 min) and
      at the end of the procedure (60 min). After the collection of last blood samples,
      all animals were killed and samples from liver and gut were obtained for
      measurements of tissue malondialdehyde levels and histology. RESULTS: The
      proinflammatory cytokine levels were increased significantly in groups 1 to 3,
      but did not change in the laparotomy group. Serum C-reactive protein levels were
      elevated in all groups. The comparison of the results between the laparotomy and
      laparoscopy groups showed that serum interleukin 6 and nitric oxide levels were
      significantly elevated in relation the intra-abdominal pressure, and serum
      interleukin 6 and nitric oxide levels peaked in group 3. Tissue malondialdehyde
      levels were significantly higher in groups 1 and 2 than in groups 3 and 4.
      CONCLUSIONS: The findings of our experiment suggest that the elevated intra
      abdominal pressure is responsible for ischemia, free radical production, and
      proinflammatory cytokine response-mediated cell damage during laparoscopic
      surgery.

PMID- 19390283
TI  - Laparoscopic radical nephrectomy for unilateral renal cancer in children.
AB  - PURPOSE: At the present time, the standard approach for renal cancer in children
      is open surgery, and the role of laparoscopic approach remains to be defined. We
      report our preliminary experience in the treatment by laparoscopic radical
      nephrectomy (LRN) for unilateral renal cancer in children. METHODS: Five
      children, whose mean age was 4 years old, were operated for unilateral renal
      malignant tumors by laparoscopic approach in our unit from October 2005 to June
      2007. Four cases were suspected of Wilms tumors and one of them presented
      bilateral lung metastases. They were preoperatively treated with chemotherapy
      according to the International Society of Pediatric Oncology 2001 protocol:
      vincristine and actinomicyn D for 4 weeks. The fifth case was a 10-year-old
      child, treated 8 years before with chemotherapy for a cerebellar vermis
      medulloblastoma history. A percutaneous biopsy was performed preoperatively and
      the histology showed a juvenile renal-cell carcinoma. All cases subsequently
      underwent LRN. Four trocars were used in each case and the tumors were placed in
      a bag before being extracted intact without morcellation through a low suprapubic
      incision. RESULTS: All tumors and lymph node samples were removed completely by
      laparoscopy without rupture. No conversion to laparotomy was necessary and there
      was neither intraoperative bleeding nor complications. The mean operative time
      was 90 minutes (60 to 117 min). Postoperatively, 1 child presented an intestinal
      perforation and suture closure was performed by laparoscopy on the third
      postoperative day; the discharge was after 10 days, and the others were
      discharged after 2 or 3 days. In all cases, the resection was microscopically
      complete. The histology was 3 unilateral Wilms tumor, 1 clear-cell sarcoma and 1
      juvenile renal-cell carcinoma with t(X;17). No lymph node was positive for the
      tumors. None of these patients presented evidence of tumoral recurrences, port
      site implantation or short-term complications at a mean of 18 months of follow-up
      (range: 12 to 32 mo). CONCLUSIONS: LRN for renal cancer in children is feasible
      after preoperative chemotherapy, with the same oncologic strategies as open
      surgery. A long follow-up and more cases are necessary to evaluate and compare
      the results of laparoscopic approach with the open procedures.

PMID- 19390284
TI  - No difference between smokers, former smokers, or nonsmokers in the operative
      outcomes of laparoscopic donor nephrectomies.
AB  - The laparoscopic donor nephrectomy has revolutionized the living donation process
      for kidney transplantation. Because this surgery is elective and altruistic and
      smoking has been associated with greater technical difficulty and increased risk
      for postoperative complications for other types of surgeries, the potential risk
      of smoking must be addressed with regard to surgical complications. We reviewed
      221 laparoscopic kidney donors with known smoking status. Forty-two (19%) were
      smokers, 39 (18%) were former smokers, and 140 (63%) were nonsmokers. Important
      donor demographics were similar between groups. There was no difference between
      the 3 groups for mean operative time (4.5 h vs. 4.6 h vs. 4.4 h), median or mean
      length of stay (2 days for all groups), estimated blood loss (173+/-137 mL vs.
      209+/-184 mL vs. 188+/-198 mL), narcotic use (0.57+/-0.48 mg/kg vs. 0.49+/-0.26
      mg/kg vs. 0.53+/-0.36 mg/kg of total 4 morphine equivalents), or postoperative
      complications. Smoking status does not seem to impact perisurgical patient
      outcomes in patients undergoing laparoscopic nephrectomies.

PMID- 19390285
TI  - Axial-spin technique of endoscopic intracorporeal knot tying: comparison with the
      conventional technique and objective assessment of knot security, learning
      curves, and performance efficiency across training levels.
AB  - INTRODUCTION: A major limitation of conventional laparoscopic surgery is the
      placement of an intracorporeal (IC) knot, which requires a significant amount of
      training and practice. An easier technique of IC knot tying using 90-degree
      grasper is compared with the conventional technique (CLT). The new axial-spin
      technique (AST) uses the spin of the instrument shaft to tie IC knots. METHODS:
      Fourteen participants stratified into 3 training levels were instructed to tie 50
      reef IC knots using each technique on trainers in 3 sessions. The final 5 knots
      tied using each technique were deemed to be representative of maximal performance
      efficiency (PE) and randomly subject to tensile strength measurements using a
      tensiometer at 50 mm/s distraction. Mean knot execution time (mKET) measured in
      seconds (s), normalized KE time (nET=group mean/mKET), knot holding capacity,
      relative knot security (RKS), and PE (PE=RKS/nET) of the knots tied were computed
      and analyzed using paired t and analysis of variance. RESULTS: Variables included
      knot-tying session, technique and the training level. On completion of the study,
      junior residents (JR) averaged 51.72 seconds more, senior residents (SR) averaged
      26.22 seconds more and attendings (ATT) averaged 19.17 seconds less to tie using
      CLT compared with the AST (F=40.52, P=0.0001). Across all levels, the CLT
      technique was taking 83.26 seconds on average to execute an IC knot compared with
      59.08 seconds with AST method (t=2.784, P=0.015). Learning curves revealed that
      JR significantly improved mean KE times with the AST technique (first session vs.
      final session: 473.8 s vs. 55.9 s) compared with CLT (672.5 s vs. 107.6 s) across
      the sessions as compared with those in advanced levels of training. The RKS of
      knots executed by AST was significantly stronger (AST: 13.1 vs. 5.44 N, t=4.9,
      P=0.0001). The PE of knots executed using the CLT increased geometrically across
      training levels (JR: 1.35% SR: 5.58% ATT: 11.22%) whereas those of AST showed a
      linear trend (17.09%; 17.11%, and 13.95%). CONCLUSION: The AST follows a linear
      pattern of learning across training levels compared with the steep exponential
      learning of the CLT. Inexperienced JRs were surprisingly 1.5 times more efficient
      with AST and 8 times less efficient with CLT compared with ATT using the CLT to
      execute the same knot. The AST is significantly easier to learn for JRs and could
      serve as a platform before acquiring more advanced knot-tying skills. Overall,
      with the AST, execution times are significantly shorter whereas the RKS and PE
      are significantly higher. JRs achieve a level of proficiency comparable with the
      senior level residents and ATT after participating in a reasonable training
      session consisting of at least 25 knots.

PMID- 19390286
TI  - Ergonomic evaluation of the scrub nurse's posture at different monitor positions
      during laparoscopic cholecystectomy.
AB  - OBJECTIVE: Our aims were to measure the posture and movement of the scrub nurse
      very accurately, without using any markers, during a minimally invasive surgical
      procedure. SUMMARY BACKGROUND DATA: One of the most important subjects in
      ergonomic studies of minimally invasive surgery is the question of the proper
      placement of monitors. METHOD: Two simultaneous and synchronized video recordings
      were carried out in 2 different monitor setups. The different steps of the
      operation were identified and measured in seconds. Longer-lasting postures were
      imported to and analyzed with a software. Results of the different setups were
      compared with each other, and with an "ideal" comfort posture. RESULTS: Measuring
      the typical postures of the most pronounced static phase, the evolving stress was
      significantly influenced by different monitor setups. CONCLUSIONS: With the
      installation of an additional monitor positioned to satisfy the nurse's comfort,
      the static stress could be decreased.

PMID- 19390287
TI  - Endovenous microwave ablation of varicose veins: in vitro, live swine model, and
      clinical study.
AB  - AIM: This study aims to investigate the application of the microwave generator to
      treat the patients with varicose veins. MATERIALS AND METHODS: Phase 1: Explanted
      saphenous veins in subcutaneous layer of the pork meat were ablated at 0, 40, 50,
      60, and 70 W. Phase 2: The forelimb veins and the hindlimb arteries of a 40-kg
      swine were ablated at 50 and 60 W. Phase 3: The patients were treated with
      endovenous microwave ablation at 50 W. RESULTS: Phase 1: Perivenous tissue injury
      was found in groups 50, 60, and 70 W. Phase 2: Less perivenous tissue injury was
      found in group 50 W. Phase 3: Complete venous occlusion rate was 65% and venous
      reflux-free was 85% in 1 year. No severe complication was found. CONCLUSIONS: The
      microwave generator with 50-W power setting could be used to ablate the varicose
      veins safely.

PMID- 19390288
TI  - Erosion of a composite PTFE/ePTFE mesh after hiatal hernia repair.
AB  - Primary repair of large hiatal defects is associated with higher than acceptable
      recurrence rates. This has led to the increased use of fascial prostheses for
      reinforcement of the hiatal repair. We report a case of intraluminal mesh erosion
      after repair of a recurrent paraesophageal hernia with a composite
      polytetrafluoroethylene/expanded polytetrafluoroethylene prosthesis in an 80-year
      old woman. Mesh erosion is a rarely reported complication after hiatal hernia
      repair, and because many cases will go unreported, their true incidence is
      unknown. Besides the durability of mesh repair, the ongoing clinical trials
      investigating laparoscopic correction of hiatal hernias should also focus on the
      risk of complications associated with the use of prosthetic materials and the
      mode of fixation.

PMID- 19390289
TI  - Some thoughts on endoscopic thyroidectomy.

PMID- 19390292
TI  - Research for improving diagnostic systems: consideration of factors related to
      later life development.

PMID- 19390293
TI  - An examination of the "gold standard" diagnosis of major depression in aged-care
      settings.
AB  - OBJECTIVES: Individual clinical interviews are typically viewed as the "gold
      standard" when diagnosing major depressive disorder (MDD) and when examining the
      validity of self-rated questionnaires. However, this approach may be problematic
      with older people, who are known to underreport depressive symptomatology. This
      study examined the effect of including an informant interview on prevalence
      estimations of MDD in an aged-care sample. DESIGN: The results of an individual
      clinical interview for MDD were compared with those obtained when an informant
      interview was incorporated into the assessment. Results from each diagnostic
      approach were compared with scores on a self-rated depression instrument.
      SETTING: Low-level aged-care residential facilities in Melbourne (equivalent to
      "residential homes," "homes for the elderly," or "assisted living facilities" in
      other countries). PARTICIPANTS: One hundred and sixty-eight aged-care residents
      (mean age: 84.68 years; SD: 6.16 years) with normal cognitive functioning.
      MEASUREMENTS: Individual clinical interviews were conducted using the Structured
      Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition Axis I Disorders. This interview was modified for use with staff
      informants. Self-reported depression was measured using the Geriatric Depression
      Scale-15 (GDS-15). RESULTS: The estimated point prevalence of MDD rose from 16%
      to 22% by including an informant clinical interview in the diagnostic procedure.
      Overall, 27% of depressed residents failed to disclose symptoms in the clinical
      interview. The concordance of the GDS-15 with a diagnosis of MDD was
      substantially lower when an informant source was included in the diagnostic
      procedure. CONCLUSION: Individual interviews and self-report questionnaires may
      be insufficient to detect depression among older adults. This study supports the
      use of an informant interview as an adjunct when diagnosing MDD among cognitively
      intact aged-care residents.

PMID- 19390294
TI  - Quantification of five neuropsychological approaches to defining mild cognitive
      impairment.
AB  - OBJECTIVES: Operational definitions of cognitive impairment have varied widely in
      diagnosing mild cognitive impairment (MCI). Identifying clinical subtypes of MCI
      has further challenged diagnostic approaches because varying the components of
      the objective cognitive assessment can significantly impact diagnosis. Therefore,
      the authors investigated the applicability of diagnostic criteria for clinical
      subtypes of MCI in a naturalistic research sample of community elders and
      quantified the variability in diagnostic outcomes that results from modifying the
      neuropsychological definition of objective cognitive impairment. DESIGN: Cross
      sectional and longitudinal study. SETTING: San Diego, CA, Veterans Administration
      Hospital. PARTICIPANTS: Ninety nondemented, neurologically normal, community
      dwelling older adults were initially assessed and 73 were seen for follow-up
      approximately 17 months later. MEASUREMENTS: Participants were classified via
      consensus diagnosis as either normally aging or having MCI via each of the five
      diagnostic strategies, which varied the cutoff for objective impairment and the
      number of neuropsychological tests considered in the diagnostic process. RESULTS:
      A range of differences in the percentages identified as MCI versus cognitively
      normal were demonstrated, ranging from 10-74%, depending on the classification
      criteria used. A substantial minority of individuals demonstrated diagnostic
      instability over time and across diagnostic approaches. The single domain
      nonamnestic subtype diagnosis was particularly unstable (e.g., prone to
      reclassification as normal at follow up). CONCLUSION: Our findings provide
      empirical support for a neuropsychologically derived operational definition of
      clinical subtypes of MCI and point to the importance of using comprehensive
      neuropsychological assessments. Diagnoses, particularly involving nonamnestic
      MCI, were variable over time. The applicability and utility of this particular
      MCI subtype warrants further investigation.

PMID- 19390295
TI  - Specific phobia in older adults: evidence from the national epidemiologic survey
      on alcohol and related conditions.
AB  - OBJECTIVE: This study aims to investigate: 1) the association of specific phobia
      with childhood parental loss and recent stressful life events; 2) the coexistence
      of specific phobia and major depressive disorders (MDDs); and 3) the impact of
      specific phobia on medical conditions, obesity, health service utilization, and
      health-related quality of life. DESIGN: Cross-sectional observational study.
      SETTING: The National Epidemiologic Survey on Alcohol and Related Conditions
      (2001-2002), a national representative survey of the noninstitutionized U.S.
      household population. PARTICIPANTS: The 8,205 respondents aged 65 and above.
      MEASUREMENTS: Specific phobia was assessed using the Alcohol Use Disorder and
      Associated Disabilities Interview Schedule-Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition version. Demographic characteristics,
      psychosocial risk factors, psychiatric disorders, health-related quality of life,
      obesity, medical conditions, and health service utilization were measured.
      RESULTS: The current and lifetime prevalence of specific phobia were 4.51% and
      6.05%, respectively. Multivariate analyses revealed that specific phobia was more
      common among younger age groups, women, and those who reported stressful life
      events but less common among foreign-born individuals. In addition, MDD was
      significantly related to lifetime specific phobia. Specific phobia was also
      significantly related to a lower health-related quality of life and two medical
      conditions. CONCLUSION: Our prevalence rates of specific phobia in the elderly
      are at the lower end of the ranges identified in the previous studies. The
      correlation between specific phobia and MDD raises further questions about the
      nature of specific phobia in the elderly. This study supports the notion that
      specific phobia has a strong impact on the quality of life in old age.

PMID- 19390296
TI  - Profiles of depressive symptoms in older adults diagnosed with major depression:
      latent cluster analysis.
AB  - OBJECTIVE: To explore the underlying structure of symptom presentation in older
      adults with major depression by identifying homogeneous clusters of individuals
      based on symptom profiles. DESIGN: Secondary data analysis using latent class
      cluster analysis. SETTING: Clinical Research Center for the Study of Depression
      in Later Life conducted at Duke University. PARTICIPANTS: Three hundred sixty-six
      patients age 60+ who met Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition (DSM-IV) criteria for major depression and were enrolled in a
      longitudinal naturalistic treatment study. MEASUREMENTS: Responses to the 10
      items of the Montgomery-Asberg Depression Rating Scale at the time of study
      enrollment. RESULTS: The authors identified four latent clusters of older adults
      with major depression. Patients in Cluster 1 (47.2%) had mean scores of average
      severity for reported and apparent sadness and lassitude and low mean scores for
      reduced appetite. Patients in Cluster 2 (27.1%) had higher mean scores compared
      with Cluster 1 for all items, and particularly for apparent sadness. Patients in
      Cluster 3 (18.9%) had the lowest mean scores for both apparent and reported
      sadness, but a similar profile compared with Cluster 1 for inner tension, reduced
      sleep, reduced appetite, and concentration difficulties. Cluster 4 (6.8%) had the
      highest mean scores for each item. Both apparent and reported sadness accounted
      for a large amount of variance among the four clusters. Patients in Cluster 4
      were more likely to have 12 or less years of education and/or one or more
      functional limitations. CONCLUSION: The heterogeneity in symptom presentation
      among older adults diagnosed with major depression can potentially inform the
      development of DSM-V.

PMID- 19390297
TI  - Differential FDDNP PET patterns in nondemented middle-aged and older adults.
AB  - OBJECTIVE: The authors explored whether positron emission tomography (PET) with 2
      (1-{6-[(2-[fluorine-18]fluoroethyl)(methyl) amino]-2-naphthyl}
      ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in
      vitro, might identify homogeneous subgroups of persons in middle-aged and older
      persons with mild cognitive impairment (MCI) or normal cognition. PARTICIPANTS:
      Fifty-six subjects (MCI, N = 29; normal cognition, N = 27). MEASUREMENTS: FDDNP
      PET scans were performed. Logan parametric images were produced using cerebellum
      as a reference region, and relative distribution volumes were obtained for
      regions of interest (ROIs) known to accumulate plaques and tangles in Alzheimer
      disease (AD). Cluster analysis was used to identify subgroups of subjects
      according to FDDNP signal distribution. Once the FDDNP clusters were identified,
      the authors then characterized the clusters also with respect to diagnosis and
      cognitive test performances and conducted analyses on cluster differences in
      these variables. RESULTS: The authors identified three FDDNP clusters: high
      signal in lateral temporal and posterior cingulate ROIs (high temporal-posterior
      cingulate HT/PC); low signal in all ROIs (low global [LG] cluster); high frontal
      and parietal signal with intermediate temporal and posterior cingulate signal
      (HF/PA). Most MCI subjects belonged to the HT/PC and HF/PA clusters, whereas most
      cognitively normal subjects were in the LG cluster. On cognitive tests, the HT/PC
      and the HF/PA clusters performed significantly worse than LG but did not
      significantly differ from each other. CONCLUSIONS: This approach may be useful in
      identifying potential high-risk imaging cluster patterns. Longitudinal follow-up
      would be performed to determine the association of these subgroups with
      diagnostic and functional outcome.

PMID- 19390298
TI  - Determinants of successful aging using a multidimensional definition among
      Chinese elderly in Singapore.
AB  - OBJECTIVE: Most studies of successful aging have used restricted definitions
      based on the absence of disability and identified a small number of predictors.
      The authors aimed to examine whether a broad multidimensional definition of
      successful aging has good construct validity and identified a wider range of
      predictors that are relevant for multifaceted interventions. METHODS: Cross
      sectional and longitudinal data analyses were performed on 1,281 community-living
      Chinese elderly of 65 years and above in the Singapore Longitudinal Aging Study
      cohort. Successful aging was measured in multiple dimensions of functioning and
      wellness: cognitive and affective status, physical health, social functioning and
      engagement and life satisfaction, and a summary composite measure created across
      dimensions to form a dichotomous variable. Potential determinants included
      sociodemographic, psychosocial, behavioral variables. RESULTS: Successful aging
      was determined in 28.6% of respondents and in multivariate models was
      significantly (p <0.05) associated with age (OR = 0.90), female gender (OR =
      1.37), > or =6 years of education (OR = 2.31), better housing (OR = 1.41),
      religious or spiritual beliefs (OR = 1.64), physical activities and exercise (OR
      = 1.90), and low or no nutritional risk (OR = 2.16). CONCLUSION: In contrast to
      findings based on more restricted biomedical definitions of successful aging, a
      multidimensional definition of successful aging identified more variables
      including demographic status, psychosocial support, spirituality, and nutrition
      as salient determinants.

PMID- 19390299
TI  - Association of antipsychotic use with hospital events and mortality among
      medicare beneficiaries residing in long-term care facilities.
AB  - OBJECTIVE: Antipsychotic (AP) utilization has grown significantly in long-term
      care (LTC) settings. Although a growing literature associates AP use with higher
      mortality in elderly with dementia, the association of APs with hospital events
      is unclear. The authors examine prevalence and trends in AP use by Medicare
      beneficiaries residing in LTC and the association of APs and other drug use
      variables with hospital events and mortality. DESIGN: Retrospective analysis
      using sequential multivariate Cox proportional hazards models. SETTING: Medicare
      Current Beneficiary Survey linked to Institutional Drug Administration and
      Minimum Data Set files. PARTICIPANTS: A total of 2,363 LTC Medicare
      beneficiaries, 1999-2002. MEASUREMENTS: Trends in LTC AP use overall and by type
      and duplicative use; association of AP utilization and two outcomes: hospital
      events and all-cause mortality. RESULTS: AP use rose markedly from 1999 to 2002
      (26.4%-35.9%), predominantly due to increased use of atypical agents. After
      controlling for sociodemographic and clinical factors, AP use is not related to
      hospital events (hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.82
      1.63 p = 0.7951). AP use is associated with reduced mortality in unadjusted and
      intermediate models, but loss of significance in the final model (HR = 0.83, 95%
      CI = 0.69-1.00, p = 0.0537) suggests that disease and drug burden factors may
      confound the AP-mortality relationship. CONCLUSION: This study provides no
      evidence of increased hospital events or mortality in LTC residents who use AP
      medications. Findings contribute to a growing body of evidence that APs,
      particularly atypical agents, may be associated with reduced mortality in LTC
      residents.

PMID- 19390300
TI  - Capacity to make treatment decisions in Chinese older persons with very mild
      dementia and mild Alzheimer disease.
AB  - OBJECTIVES: This study aims at assessing mental competence in Chinese patients
      with mild and very mild dementia with a semistructured assessment method and the
      impact of repeated presentations of information on patients' mental competence.
      DESIGN: Subjects with mild and very mild dementia were compared with cognitively
      intact subjects. SETTING: Chinese subjects were recruited from local social
      centers and residential hostels for the elderly in Hong Kong. PARTICIPANTS: Sixty
      six Chinese community-dwelling older adults (aged from 65 to 87 years) were
      recruited. MEASUREMENTS: Clinical diagnosis was made by experienced geriatric
      psychiatrists. Subjects were assessed with the Mini-Mental State Examination and
      the Clinical Dementia Rating (CDR). Mental capacity to consent to treatment was
      assessed by using the Chinese version of the MacArthur Competence Assessment Tool
      Treatment (MacCAT-T) and independent clinician ratings based on the definition in
      the Mental Capacity Act 2005 of the United Kingdom. RESULTS: Thirty-three (50%)
      participants were diagnosed with very mild or mild dementia (CDR = 0.5 or 1). In
      this group, 15 (45.5%) subjects were rated as mentally incompetent in clinician
      ratings. In the assessment of interrater reliability, the intraclass correlation
      coefficient of MacCAT-T summary scores among three raters ranged from 0.64 to
      0.83. The MacCAT-T summary scores correlated significantly with clinician
      ratings, years of education, Mini-Mental State Examination score, and CDR. In
      contrast to the nonimpaired group, repeated presentation of information did not
      significantly improve capacity in the demented group. CONCLUSION: Results from
      this study suggest that even patients with very mild dementia in this population
      can show substantial deficits in decision-making capacity, and that improved
      capacity is not likely to result from repeated disclosure of information.

PMID- 19390301
TI  - The utility of a brief memory screen in the diagnosis of mild memory impairment
      in the elderly: preliminary study.
AB  - OBJECTIVE: This study evaluated the utility of the Florida Brief Memory Screen
      (FBMS), a new memory screening measure developed for Spanish-speaking and English
      speaking subjects, which takes only 3-4 minutes to administer. METHODS: The FBMS
      was administered to 25 patients with probable Alzheimer disease, 23 patients with
      amnestic mild cognitive impairment, and 80 cognitively normal elderly. RESULTS:
      The FBMS evidenced good test-retest reliability and high correlation with
      standard measures of memory. In receiver operating characteristic analyses, the
      FBMS correctly classified 100% of patients with probable Alzheimer disease and
      87.5% of normal elderly subjects. Sensitivity and specificity for patients with
      amnestic mild cognitive impairment was 82.6% and 87.5%, respectively. Performance
      on the FBMS was generally independent of the effects of age, education, or
      primary language. CONCLUSION: The FBMS is a reliable and a valid measure when
      screening for memory impairment in the elderly and when determining whether a
      more extensive evaluation is warranted.

PMID- 19390302
TI  - Hormone replacement therapy: real concerns and false alarms.
AB  - From 2002 to 2008, reports from the Women's Health Initiative (WHI) claimed that
      hormone replacement therapy (HRT) significantly increased the risks of breast
      cancer development, cardiac events, Alzheimer disease, and stroke. These claims
      alarmed the public and health professionals alike, causing an almost immediate
      and sharp decline in the numbers of women receiving HRT. However, the actual data
      in the published WHI articles reveal that the findings reported in press releases
      and interviews of the principal investigators were often distorted,
      oversimplified, or wrong. This review highlights the history of research on HRT,
      including a timeline of studies that have or have not found a link between HRT
      and breast cancer; discusses how to distinguish important, robust findings from
      those that are trivial; closely examines the WHI findings on HRT and breast
      cancer, most of which are weak or statistically insignificant; reviews the
      current thinking about possible links of HRT with cardiovascular disease and
      cognitive functioning; and reports research on the benefits of HRT, notably
      relief of menopausal symptoms, that affect a woman's quality of life. On these
      complicated matters, physicians and the public must be cautious about accepting
      "findings by press release" in determining whether to prescribe or take HRT.

PMID- 19390303
TI  - An update on the use of intraperitoneal chemotherapy in the management of ovarian
      cancer.
AB  - The intraperitoneal delivery of chemotherapy as a strategy to manage epithelial
      ovarian cancer has been extensively examined in both the preclinical and clinical
      settings. Several randomized phase 3 trials have documented improved survival
      associated with regional versus systemic delivery of cisplatin in the primary
      chemotherapeutic management of small volume residual advanced ovarian cancer.
      Unfortunately, despite the existence of these evidence-based data, this
      management strategy remains underutilized. Future research efforts are mandated
      to develop regimens which improve the toxicity profile of this novel method of
      treatment while maintaining the documented enhanced efficacy of the approach.

PMID- 19390304
TI  - KRAS mutations and susceptibility to cetuximab and panitumumab in colorectal
      cancer.
AB  - Recent retrospective evidence from several randomized studies has established
      that advanced colorectal cancer patients with tumors harboring a mutation in the
      KRAS gene do not derive benefit from the administration of epidermal growth
      factor receptor-directed monoclonal antibodies, such as cetuximab or panitumumab.
      This represents a paradigm-changing event and will have substantial impact on
      current and future anticancer drug development. These results add to the economic
      and ethical considerations involved in the development of novel targeted
      therapies and should increase our scrutiny of mechanisms of resistance and
      predictive biomarkers while in earlier developmental stages. In this article, we
      will review the available clinical data and discuss the implications for future
      drug development in colorectal cancer.

PMID- 19390305
TI  - From the guest editor: Hodgkin's lymphoma: an overview.

PMID- 19390306
TI  - Current insight on trends, causes, and mechanisms of Hodgkin's lymphoma.
AB  - Hodgkin's lymphoma (HL) has a unique and distinct history, epidemiology,
      treatment, and biology. A viral agent or infectious agent has long been
      considered as the etiologic agent and Epstein-Barr virus is the main candidate
      for the infectious agent causing HL; however, Epstein-Barr virus genome is found
      within the tumor in only about 20% to 40% of HL cases with a prior diagnosis of
      infectious mononucleosis. Recently, autoimmune and related conditions have drawn
      attention to a potential role for immune-related and inflammatory conditions in
      the etiology and pathogenesis of the malignancy. Evidence from multiply-affected
      families, a twin study, a case-control study, and population-based registry
      studies implicate genetic factors. Data from Eastern Asia and among Chinese
      immigrants in North America indicate increasing incidence trends for HL being
      associated with westernization. These results emphasize an interaction between
      environmental and genetic risk factors in HL.

PMID- 19390307
TI  - Clinical manifestations and natural history of Hodgkin's lymphoma.
AB  - Hodgkin's lymphoma usually presents with typical lymphadenopathy that has been
      detected either incidentally by the patient or by imaging procedures performed
      for assessment of other conditions. Occasionally, it may be detected when
      investigation of nonspecific symptoms, such as fever, fatigue, or unexplained
      pain prompt assessment that, in turn reveals a mass lesion. The diagnosis must be
      confirmed with an appropriate biopsy. Nowadays, clinicians usually have little
      difficulty making the diagnosis of Hodgkin's lymphoma. Knowledge of the usual
      pattern of spread of this lymphoma, with its orderly progression through lymph
      node groups and its typical forms of extranodal involvement, facilitates timely
      diagnosis, staging, and treatment planning. Rare manifestations due to
      involvement of unusual sites or presentation with paraneoplastic organ
      dysfunction can prove challenging but a search for mass lesions and an
      appreciation of these uncommonly encountered findings as potential clues to the
      presence of Hodgkin's lymphoma usually prompts appropriate investigation and
      correct diagnosis. Finally, an understanding of the usual pattern and timing of
      relapse and knowledge of the typical types of late toxicity expected after
      successful eradication of the lymphoma allow the patient's physicians to detect
      recurrence in a timely fashion and to identify or prevent secondary complications
      enabling appropriate management plans to be developed.

PMID- 19390308
TI  - Histopathology of Hodgkin's lymphoma.
AB  - In the last few years, there has been a greater understanding of the spectrum and
      biology of Hodgkin's lymphoma. In standard texts, Hodgkin's lymphoma is
      classified as 2 distinct entities, namely nodular lymphocyte predominant
      Hodgkin's lymphoma and classical Hodgkin's lymphoma. However, recent evidence
      suggests that classical Hodgkin's lymphoma is not a single disease. Although the
      mixed cellularity and lymphocyte-depleted subtypes may be part of a biologic
      continuum, the nodular sclerosis subtype has a distinct epidemiology, clinical
      presentation, and histology. Nodular sclerosis Hodgkin's lymphoma, particularly
      those cases presenting with mediastinal disease, also seems related to primary
      mediastinal B-cell lymphoma. As Hodgkin's lymphoma is a B-cell neoplasm, there is
      also a better appreciation today of cases that may be borderline with
      conventional B-cell lymphomas. We present an update on the histopathological
      features of Hodgkin's lymphoma and the immunohistochemical tools available for
      diagnosis in the clinical setting.

PMID- 19390309
TI  - Hodgkin's lymphoma--patient's assessment and staging.
AB  - Hodgkin's lymphoma is one of the most curable malignancies today. But treatment
      is associated with significant toxicity. The objective of high-quality management
      is to minimize treatment exposure while maximizing cure of disease. Principles of
      cancer staging and patient's assessment taxonomy are important to improve
      communication. An orderly patient evaluation and systematic recording of disease
      extent using the Ann Arbor classification forms the basis for treatment decision,
      response assessment, and clinical trials. The practice of staging in Hodgkin's
      lymphoma evolved over the past 40 years from clinical examination and plain
      imaging to modern anatomic and functional imaging. Although useful in the past,
      staging laparotomy, lymphangiograms, and Gallium scintigraphy have now been
      abandoned. Computerized tomography combined with 2-[18F]fluoro-2-deoxyglucose
      positron emission tomography form the basis for anatomic disease extent
      assessment. Although patients' evaluation and staging at diagnosis are important,
      the management of Hodgkin's lymphoma involves a complex series of algorithms
      requiring interim and overall response assessment, careful follow-up, repeat
      assessment, and salvage management of recurrent disease.

PMID- 19390310
TI  - Combined modality treatment of Hodgkin's lymphoma.
AB  - Substantial clinical progress over the last decades has improved the first-line
      treatment and prognosis of patients with Hodgkin's lymphoma (HL). This success is
      mainly based on the introduction of combined modality treatment strategies
      including chemotherapy in all risk groups and important progress in radiation
      techniques. The knowledge emerging from numerous clinical trials as well as
      better staging and imaging techniques helped to develop more effective therapies.
      According to our current knowledge, a stage and risk factor-based allocation into
      early favorable, early unfavorable, and advanced stages remains a suitable
      instrument to tailor risk-adapted therapy. In most of the study groups, patients
      with early stage HL receive 2 to 4 cycles of chemotherapy followed by
      radiotherapy to the involved field. The treatment for advanced stages usually
      consists of 6 to 8 cycles, more intensive regimen, and radiotherapy for residual
      masses. Here, we review results from current clinical trials and discuss new
      therapeutic approaches in the combined modality treatment of HL.

PMID- 19390311
TI  - Role of chemotherapy in Hodgkin's lymphoma.
AB  - The development of curative chemotherapy regimens for the treatment of Hodgkin's
      lymphoma (HL) is one of the true success stories in oncology. Most patients
      diagnosed with HL today can be cured. The major task remaining before us is
      curing as many patients as possible with their initial therapeutic approach while
      minimizing the acute toxicities and limiting the lifetime risks of important
      secondary events such as cardiovascular complications and secondary malignancies.
      In the 40 years since DeVita et al. developed the mechlorethamine, vincristine,
      procarbazine, and prednisone chemotherapy regimen, we have learned a great deal
      about risk stratification to minimize treatment-related toxicity. Positron
      emission tomography may further assist us in reducing radiation treatment without
      compromising cures. This review will discuss the development of the chemotherapy
      regimens used in the management of early and advanced stage HL and the advantages
      and disadvantages of their use in combination with radiation therapy.

PMID- 19390312
TI  - Role of radiation therapy in Hodgkin's lymphoma.
AB  - Radiation therapy was the first modality that solely cured patients with
      Hodgkin's lymphoma (HL) as early as the 1940s. In the absence of other curative
      options, the radiation field in full dose was extended to encompass both involved
      and uninvolved sites including many normal organs. Decades later, it was evident
      that some of the HL survivors succumbed to radiation-related effects, mostly
      second solid tumors. The more recent reliance on modern chemotherapy in
      combination with radiation yielded further improvement in disease control and
      allowed a marked reduction in radiation exposure. Some oncologists even suggested
      that chemotherapy alone might retain the excellent results obtained with combined
      modality and campaigned for the exclusion of radiotherapy from the treatment
      program. However, analysis of randomized studies (as discussed later) supports
      the inclusion of reduced-field and dose radiotherapy in treatment programs for
      HL. Furthermore, new concerns regarding the short- and long-term safety of
      enhancing chemotherapy to compensate for the omission of radiotherapy favor
      shorter courses of chemotherapy. Short chemotherapy supplemented with mini
      radiotherapy constitutes a highly effective and safe treatment of HL,
      particularly in early stages.

PMID- 19390313
TI  - Salvage therapy for Hodgkin's lymphoma.
AB  - Hodgkin's lymphoma (HL) is a clonal lymphoid malignancy that affects over 7000
      patients in the United States annually. The disease remains one of the great
      success stories in the recent history of cancer treatment. More than 80% of HL
      patients will be expected to be long-term survivors because of recent advances in
      radiation therapy and combined chemotherapy. However, for the subset of patients
      who relapse after initial therapy, HL remains a challenging disease. Indeed, for
      patients who relapse after salvage high-dose chemotherapy and autologous stem
      cell transplant, effective therapeutic options remain limited, and further new
      therapies are warranted. This article provides a review of the current literature
      regarding salvage therapy for HL.

PMID- 19390319
TI  - A message from the publisher.

PMID- 19390314
TI  - Late effects of Hodgkin's disease and its treatment.
AB  - Long-term survivors of Hodgkin's lymphoma are at increased risk for a number of
      late complications, including development of second malignancies and
      cardiovascular disease. Treatment-related factors and other modifying risk
      factors contributing to the risk of late effects have been identified. Survivors
      deemed at increased risk based on their treatment history and other exposures may
      benefit from early detection for late complications and risk reduction
      strategies. However, the optimal screening tests and prevention program, and
      their timing and frequency are not clear. It should be noted that treatment for
      Hodgkin's lymphoma has undergone considerable changes over the last several
      decades. Most of the current data on late effects after Hodgkin's lymphoma are
      based on patients treated with outdated chemotherapy and radiation therapy. As
      Hodgkin's lymphoma therapy evolve over time, continued documentation of late
      effects associated with newer treatment will be important for the follow-up of
      patients treated in the modern era.

PMID- 19390321
TI  - Adrenal incidentalomas and subclinical Cushing's syndrome: diagnosis and
      treatment.
AB  - PURPOSE OF REVIEW: Adrenal incidentaloma has become a frequent clinical dilemma.
      Even in the absence of specific clinical features of Cushing's syndrome,
      adrenocortical incidentalomas may display steroid secretory activity at different
      degrees. The recognition of endocrine and metabolic dysfunctions associated with
      subclinical hypercortisolism leads to current awareness about its potential
      consequences. RECENT FINDINGS: Different protocols and threshold values to define
      normal cortisol secretion and diagnosis of subclinical Cushing's syndrome have
      been proposed, including recent practice guidelines for the diagnosis of overt
      Cushing's syndrome. Follow-up studies have provided additional data about the
      natural course of the disease and related cardiovascular and metabolic
      consequences. The study of bilateral adrenocorticotropin-independent macronodular
      adrenocortical hyperplasia in some familial cases offers a new approach to
      understanding the spectrum of subclinical cortisol hypersecretion. SUMMARY: The
      prevalence of subclinical hypercortisolism may be higher than previously reported
      as more sensitive diagnostic criteria are now recommended. The absence of a
      single gold standard test, the diversity of diagnostic criteria and the
      requirement of subsequent meticulous biochemical evaluations before a decision
      for treatment represent a challenge for the clinical management of this
      condition.

PMID- 19390322
TI  - Androgens and polycystic ovary syndrome.
AB  - PURPOSE OF REVIEW: Polycystic ovary syndrome (PCOS) is a common complex endocrine
      genetic disorder, which involves overproduction of androgens, leading to
      heterogeneous range of symptoms and associated with increased metabolic and
      cardiovascular morbidity. This review focuses on androgen biosynthesis, use,
      metabolism in PCOS and clinical consequences of hyperandrogenism. RECENT
      FINDINGS: Controversial definition of the disorder and different phenotypic
      subgroups present a challenge for clinical and basic research. Further
      investigation of different phenotypes highlights the fact that PCOS probably
      represents a group of disorders with different etiologies. Prenatal androgen
      exposure and adolescent studies suggest early in life androgen excess as
      initiating factor of PCOS, but insufficient evidence available to confirm this
      hypothesis. Various intracellular signaling pathways implicated in PCOS
      steroidogenesis and in androgen action have been studied, however, PCOS
      pathogenesis remains obscure. Growing evidence links androgens with
      pathophysiology of PCOS and metabolic derangements. SUMMARY: Despite intensive
      investigation, etiology and underlying mechanisms of PCOS remain unclear,
      warranting further investigation. Better understanding of molecular and genetic
      basis might lead to invention of novel therapeutic approaches. Long-term
      interventional studies that lower androgen levels in women with hyperandrogenism
      might protect against metabolic and cardiovascular comorbidities are needed.

PMID- 19390323
TI  - Androgens and ageing of the skin.
AB  - PURPOSE OF REVIEW: This study reviews current advances in our understanding of
      the role of androgens in the initiation of skin ageing. RECENT FINDINGS: Skin and
      its appendages being a steroidogenic tissue itself can be affected to a large
      extent by sex steroids. Amongst them, androgens display a distinguished role.
      They modulate epidermal and dermal thickness as proven in a variety of studies
      measuring gender-specific differences. With advanced age, changes in the
      circulating androgen levels may alter not only the morphology but also key
      functions of the skin such as epidermal barrier homeostasis and wound healing,
      sebaceous gland growth and differentiation and hair growth. SUMMARY:
      Consequently, skin becomes susceptible to infections and several disease states.
      Androgen treatment has been proposed to be an effective way to reverse the age
      associated deterioration of skin; however, further research is needed to
      translate current findings to clinically significant diagnostic and therapeutic
      applications.

PMID- 19390324
TI  - Current world literature.

PMID- 19390326
TI  - Role of beta-defensin-1 polymorphisms in mother-to-child transmission of HIV-1.
AB  - BACKGROUND AND OBJECTIVES: Mother-to-child transmission (MTCT) of HIV-1, the main
      source of pediatric AIDS, is multifactorial. Defensins provide microbial barriers
      and function as effectors of innate immunity. This study investigated the
      relationship between genetic variants of beta-defensin-1 gene and MTCT of HIV-1.
      PATIENTS AND METHODS: Three hundred children, 118 HIV-1 infected and 182 HIV-1
      uninfected, born to HIV-1-infected mothers who had not undergone antiretroviral
      therapy during pregnancy, and 84 HIV-1-infected mothers were analyzed. The single
      nucleotide polymorphisms -44C/G (rs1800972) and -52G/A (rs1799946) were genotyped
      by TaqMan allelic discrimination assay and sequencing. Statistical analyses were
      performed using SNPStats and Bonferroni correction for multiple tests. RESULTS:
      In children, the -52GG genotype and the -44G/-52G haplotype had a protective role
      against HIV-1 infection [odds ratio (OR) = 0.52, 95% confidence interval (CI)
      0.31 to 0.86, P = 0.03 and OR = 0.50, 95% CI 0.31 to 0.83, P = 0.014,
      respectively]. In mothers, the -52GG genotype and the -44G/-52G haplotype were
      associated with low levels of HIV-1 plasma viremia (<1000 copies/mL) and a lower
      risk of maternal HIV-1 transmission (OR = 0.14, 95% CI 0.03 to 0.67, P = 0.009
      and OR = 0.23, 95% CI 0.08 to 0.66, P = 0.012, respectively). CONCLUSIONS: These
      results demonstrate a significant relationship between genetic variants of beta
      defensin-1 gene, viral load, and MTCT of HIV-1, thus supporting a critical role
      of innate immunity in pediatric HIV-1 infection.

PMID- 19390328
TI  - Presence of HIV-1 R5 viruses in cerebrospinal fluid even in patients harboring
      R5X4/X4 viruses in plasma.
AB  - BACKGROUND: HIV-1 viruses have the ability to use CCR5 or CXCR4 coreceptors
      either solely (R5 or X4) or in combination (R5X4). The CCR5 antagonists block HIV
      entry into the cell and are specifically active against HIV-1 R5 strains. The
      objectives of this study were to investigate the predicted tropism of viruses
      present in paired cerebrospinal fluid (CSF) and plasma in a group of 22 HIV-1
      infected patients with neurological disorders and to search for eventual
      discordance of predicted virus tropism between both compartments. METHODS: Paired
      CSF and plasma samples were selected from subjects harboring neurological
      disorders. V3 env was amplified and bulk sequenced, and HIV-1 coreceptor usage
      was determined from the V3 env region sequence by Geno2Pheno and position
      specific scoring matrices (PSSM) algorithms. RESULTS: The majority of subjects
      (19 of 22) had concordant virus predicted tropism in both compartments. All
      patients having R5-tropic viruses in plasma had R5-tropic viruses in CSF (17 of
      22). Patients having R5X4/X4-tropic viruses in plasma could have R5X4/X4-using (2
      of 22) or R5-tropic viruses (3 of 22) in CSF. The case of R5-tropic viruses in
      plasma and R5X4/X4-tropic viruses in CSF was never observed. CONCLUSIONS: The
      majority of these patients have R5-using viruses in CSF that is mainly concordant
      with the predicted tropism in plasma. However, R5X4/X4 tropism in plasma does not
      necessarily mean the same predicted tropism in CSF compartment. Then, clinical
      therapeutic trials testing the clinical response to the CCR5 antagonists in
      patients with neurological disorders could be envisaged to analyze the effects of
      this therapeutic class in this setting.

PMID- 19390329
TI  - Soluble IL-7Ralpha (sCD127) and measurement of IL-7 in the plasma of HIV
      patients.

PMID- 19390327
TI  - Efficacy and safety of switching from boosted lopinavir to boosted atazanavir in
      patients with virological suppression receiving a LPV/r-containing HAART: the
      ATAZIP study.
AB  - OBJECTIVES: To evaluate the efficacy and safety of switching from boosted
      lopinavir (LPV/r) to boosted atazanavir (ATV/r) in virologically suppressed HIV-1
      infected patients versus continuing LPV/r. METHODS: Forty-eight weeks analysis of
      a randomized, open-label, noninferiority trial including patients with
      virological suppression (< or = 200 copies/mL for > or = 6 months) on LPV/r
      containing triple highly active antiretroviral therapy. Patients (n = 248) were
      randomized 1:1 either to continue LPV/r twice a day (n = 127) or to switch to
      ATV/r every day (ATV/r; n = 121), with no change in nucleoside reverse
      transcriptase inhibitor backbone. Those known to have >4 protease inhibitor (PI)
      associated mutations and/or who had failed >2 PI-containing regimens were
      excluded. RESULTS: Baseline characteristics were balanced. 30% harboured > or = 1
      PI-associated mutation (10% harboured > or = 1 major mutation). Treatment failure
      at 48 weeks (primary end point) occurred in 20% (25 of 127) of the LPV/r arm and
      in 17% (21 of 121) of the ATV/r arm (difference -2.3%; 95% confidence interval: 
      12.0 to 8.0; P = 0.0018). Virological failure occurred in 7% (9 of 127) of the
      LPV/r arm and in 5% (6 of 121) of the ATV/r arm (difference -2.1%; 95% confidence
      interval: -8.7% to 4.2%, P < 0.0001 for noninferiorating). CD4 changes from
      baseline were similar in each arm (approximately 40 cells/mm). Adverse event rate
      leading to study drug discontinuation was 5% in both arms. Median fasting
      triglycerides and total cholesterol decreased significantly in the ATV/r arm (-53
      and -19 mg/dL, respectively versus -4 and -4 mg/dL in the LPV/r arm; P < 0.001 in
      both comparisons). Alanine aminotransferase/aspartate aminotransferase hepatic
      abnormalities were similar in the 2 arms. CONCLUSIONS: Switching to ATV/r in
      virologically suppressed patients who were receiving a LPV/r-containing highly
      active antiretroviral therapy provided comparable (noninferior) efficacy and a
      safety profile with improved lipid parameters [ISRCTN24813210].

PMID- 19390330
TI  - Combined antiretroviral treatment initiation during hospitalization: outcomes in
      South African adults.

PMID- 19390331
TI  - Detection of hepatitis C mutants with natural resistance to NS3/4A protease
      inhibitors in HIV/HCV-coinfected individuals treated with antiretroviral therapy.

PMID- 19390332
TI  - Uptake of male circumcision in an HIV vaccine efficacy trial.

PMID- 19390335
TI  - Commentary on "Depression and coping in heart failure patients: a review of the
      literature," published in issue 24:2.

PMID- 19390336
TI  - Longitudinal cognitive performance in older adults with cardiovascular disease:
      evidence for improvement in heart failure.
AB  - BACKGROUND: Cardiovascular disease (CVD) and particularly heart failure (HF) have
      been associated with cognitive impairment in cross-sectional studies, but it is
      unclear how cognitive impairment progresses over time in older adults with these
      conditions. OBJECTIVE: The aim of this study was to prospectively examine
      cognitive function in patients with HF versus other forms of CVD. METHOD: Seventy
      five older adults (aged 53-84 years) with CVD underwent Doppler echocardiogram to
      evaluate cardiac status and 2 administrations of the Dementia Rating Scale (DRS),
      a test of global cognitive functioning, 12 months apart. RESULTS: Although DRS
      performance did not statistically differ between groups at either administration,
      a significant between-group difference in the rate of cognitive change emerged
      (lambda = 0.87; F = 10.50; P = .002; omega 2 = 0.11). Follow-up analyses revealed
      that patients with HF improved significantly on global DRS performance, whereas
      patients with other forms of CVD remained stable. More specifically, patients
      with HF showed improvement on subscales of attention, initiation/perseveration,
      and conceptualization. Exploratory analyses indicated that higher diastolic blood
      pressure at baseline was associated with improved DRS performance in patients
      with HF (r = 0.38; P = .02). CONCLUSIONS: Patients with HF exhibited modest
      cognitive improvements during 12 months, particularly in attention and executive
      functioning. Higher diastolic blood pressure at baseline was associated with
      improvement. These results suggest that cognitive impairment in patients with HF
      may be modifiable and that improved blood pressure control may be an important
      contributor to improved function. Further prospective studies are needed to
      replicate results and determine underlying mechanisms.

PMID- 19390337
TI  - Coronary artery bypass graft surgery: exploring a broader perspective of risks
      and outcomes.
AB  - Although the literature is replete with evidence related to physiological
      predictors and short-term outcomes of coronary artery bypass graft (CABG)
      surgery, there is still a paucity of data that encompass a broader perspective of
      risk and outcomes. The primary objective of this prospective cohort study was to
      explore the physiological and psychosocial dimensions of preoperative status that
      may be predictive of the short- and longer term outcomes of CABG surgery.
      Patients (N = 136) scheduled for elective/urgent CABG surgery were followed from
      the time of placement on the waiting list until 6 months after the surgery.
      Significant predictors of intensive care unit length of stay (LOS) included the
      following: age, urgency of operation, and perioperative complications. Hospital
      LOS was best predicted by baseline unemployment, longer bypass time, and
      perioperative complications. Baseline unemployment and less optimism regarding
      surgery outcomes were predictive of postdischarge home care utilization. Lower
      baseline physical functioning predicted postdischarge emergency room visits. Sex
      and baseline mental status predicted quality of life/health satisfaction scores
      at 6 weeks and 6 months after discharge. The ability to predict patient outcomes
      has implications for program planning, patient education, and policy development.
      The findings of this study provide rationale for clinicians, educators, and
      administrators to consider a broader scope of physiological and psychosocial
      parameters to predict outcomes of CABG surgery. Although the sample size was
      relatively small, the broader perspective on risk and outcomes provides insight
      for strategies to optimize overall outcomes for the CABG surgery population.
      These findings also establish the cornerstone for ongoing CABG surgery outcomes
      evaluation and research.

PMID- 19390339
TI  - A technological life buoy: patient perceptions of the Health Buddy.
AB  - BACKGROUND: Technology in healthcare takes many forms and is growing rapidly. Few
      studies have considered the acceptability, benefits, and barriers perceived by
      clients involved in the use of technology. The purpose of this study was to
      discover perceptions about ease of use, efficacy, and difficulties encountered by
      patients who used an in-home telehealth communication device, the Health Buddy.
      METHODS: Thirteen participants were selected from a parent study in which they
      used the Health Buddy. Focus groups and individual interviews were the data
      collection methods. Content analysis was used to answer the research questions.
      RESULTS: Participants found that the Health Buddy is technologically easy to use;
      that it promoted, taught, and supported heart failure self-management; and that
      it was even a "lifesaver," but that it could be bothersome, complex, and too
      lengthy an intervention. CONCLUSIONS: Telehealth, a cost-effective way to promote
      improved health management, is suitable to most patients. Minor adjustments in
      management will be needed to accommodate individual preferences to increase
      satisfaction.

PMID- 19390340
TI  - Patient-assisted computerized education for recipients of implantable
      cardioverter defibrillators: a randomized controlled trial of the PACER program.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Patients with implantable cardioverter
      defibrillators (ICDs) are at risk for postimplant anxiety. Computerized
      treatments for anxiety are well supported and desirable because of accessibility,
      anonymity, and cost-effectiveness. However, there currently exists no
      computerized psychosocial treatment for ICD populations. Our objective was to
      evaluate whether a pilot program (patient-assisted computerized education for
      recipients of ICDs [PACER of ICDs]) of a computerized intervention for ICD
      patients would improve ICD-related knowledge and psychological outcomes versus
      usual care. Outcomes were also compared with those from a related study that used
      the same intervention but in an in-person format. SUBJECTS AND METHODS: Patients
      (N = 30) with an ICD were randomized to PACER or usual care. Mean time from
      implantation was 10.71 months (SD, 21.81 months). Outcomes included ICD-related
      knowledge, trait anxiety, defibrillation-related anxiety, patient acceptance of
      the ICD, and quality of life. Patients were assessed at baseline and at 1 month
      follow-up. RESULTS AND CONCLUSIONS: Knowledge score over time did not differ by
      treatment group, although both groups improved their scores. Among treatment
      patients, increased knowledge accounted for a significant amount of variance in
      device acceptance (R2 change = 0.30, P =.02), irrespective of age, education,
      ejection fraction, and time from implantation. There was no relationship between
      knowledge and device acceptance among control patients. Compared with previous
      recipients, new device recipients (< 3 months) were more likely to demonstrate an
      increase in knowledge (P =.01), greater defibrillation anxiety (P =.02), and
      worse patient acceptance (P =.04). Patient-assisted computerized education for
      recipients of ICDs resulted in comparable improvements in trait anxiety, quality
      of life, and device acceptance as the in-person treatment. The potential utility
      of PACER to enhance device acceptance lends support for further testing among
      larger samples.

PMID- 19390338
TI  - Reduced body weight and adiposity with a high-protein diet improves functional
      status, lipid profiles, glycemic control, and quality of life in patients with
      heart failure: a feasibility study.
AB  - BACKGROUND: The effectiveness of high-protein (HP) diets in reducing body weight
      and adiposity and potentially improving clinical outcomes in heart failure (HF)
      is not known. OBJECTIVE: This feasibility study was conducted to evaluate the
      impact of 3 dietary interventions on body weight and adiposity, functional
      status, lipid profiles, glycemic control, and quality of life (QOL) in overweight
      and obese patients with HF and type 2 diabetes mellitus. DESIGN: Fourteen
      patients with HF with a body mass index greater than 27 kg/m2 were randomized to
      an HP diet, a standard protein diet, or a conventional diet. Data were obtained
      at baseline and 12 weeks. RESULTS: There were no significant differences in age
      (59 +/- 10 years), sex (78% male), New York Heart Association class (43% class
      II, 57% class III), and HF etiology or left ventricular ejection fraction (26 +/-
      7) between the groups at baseline. Patients on the HP diet demonstrated
      significantly greater reductions in weight (P = .005), percent body fat (P =
      .036), total cholesterol (P = .016), triglyceride concentrations (P = .034), and
      low-density lipoprotein cholesterol (P = .041) and greater improvements in
      functional status (6-minute walk [P = .010] and VO2 peak [P = .003]), high
      density lipoprotein cholesterol (P = .006), and physical QOL scores (P = .022)
      compared with those on standard protein and conventional diets. CONCLUSION: A 12
      week HP diet resulted in moderate weight loss and reduced adiposity in a small
      sample of overweight and obese patients with HF that were associated with
      improvements in functional status, lipid profiles, glycemic control, and QOL.
      However, these preliminary findings must be confirmed in studies with more
      participants and long-term follow-up.

PMID- 19390341
TI  - Health-related quality of life 2 years after coronary artery bypass graft
      surgery.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: The primary objective of this longitudinal
      study was to examine patient-perceived health-related quality of life (HRQOL) and
      depressive symptoms 2 years after coronary artery bypass graft surgery (CABGS)
      compared with the results from preoperative and 1 year postoperative data and to
      compare the 2-year follow-up data with Australian population normative scores.
      SUBJECTS AND METHODS: Eighty-seven participants were recruited preoperatively,
      and their HRQOL was assessed before, 6 weeks, 1 year, and 2 years postoperatively
      using the Short Form-36 (SF-36) health survey questionnaire and the Beck
      Depression Inventory. RESULTS AND CONCLUSIONS: Forty-eight participants completed
      both questionnaires 2 years after CABGS. Short Form-36 mean scores indicated an
      overall improvement in all aspects of HRQOL, with a statistically significant
      improvement in 5 of the SF-36 health domains and in the physical component
      summary (P <or= .05). Comparison of 1- and 2-year SF-36 scores revealed a
      moderate, nonsignificant deterioration in 6 of the health domains and in the
      physical component summary, whereas Mental Health and the Mental Component
      Summary showed a moderate, nonsignificant improvement. Two-year postoperative SF
      36 scores were similar to normative scores of the Australian population with
      heart disease. Beck Depression Inventory mean scores were within the normal range
      (<or=9) at 2 years postoperatively and not significantly different from
      preoperative scores. The research has indicated that most of the participants had
      significant improvements in their perceived health status 2 years after CABGS and
      no significant depressive symptoms had been noted; however, it also raises
      questions as to why there may be some deterioration in health status between 1
      and 2 years postoperatively. This has important implications for the planning of
      nursing care and patient education after CABGS.

PMID- 19390342
TI  - Cognitive deficits in heart failure: Re-cognition of vulnerability as a strange
      new world.
AB  - BACKGROUND: Patients with chronic heart failure (HF) have impairment in memory,
      psychomotor speed, and executive function. OBJECTIVE: The aim of this study was
      to describe how individuals with HF and cognitive deficits manage self-care in
      their daily lives. METHODS: Using an interpretive phenomenology method, HF
      patients completed unstructured face-to-face interviews about their ability to
      manage complex health regimens and maintain their health-related quality of life.
      Analysis of data was aided by use of Atlas.ti computer software. RESULTS: The
      sample consisted of 12 patients (10 men; aged 43-81 years) who had previously
      undergone neuropsychological testing and were found to have deficits in 3 or more
      cognitive domains. Patients confirmed that they followed the advice of healthcare
      providers by adherence to medication regimens, dietary sodium restrictions, and
      HF self-care. One overarching theme was identified: "Re-cognition of
      Vulnerability: A Strange New World." This theme was further differentiated into 3
      components: (1) not recognizing cognitive deficits; (2) recognizing cognitive
      deficits, described as (a) never could remember anything, (b) just old age, (c)
      HF-related change, and (d) making normal accommodations; and (3) recognizing
      vulnerability, explained by perception of (a) cognitive, (b) physical, and (c)
      social vulnerabilities, as well as perception of (d) the nearness of death.
      DISCUSSION: Although the study was designed to focus on the cognitive changes in
      HF patients, it was difficult to separate cognitive, physical, and social
      challenges. These changes are most useful when taken as a constellation.
      Healthcare professionals can use the knowledge to identify problems and
      interventions for HF patients.

PMID- 19390343
TI  - Progress in prevention: imperative to improve care transitions for cardiovascular
      patients.

PMID- 19390344
TI  - American Heart Association: Scientific Council of Cardiovascular Nursing.

PMID- 19390346
TI  - Calcium-independent phospholipases in the heart: mediators of cellular signaling,
      bioenergetics, and ischemia-induced electrophysiologic dysfunction.
AB  - Myocardial function is intimately dependent on the precise spatiotemporal
      regulation of membrane-bound proteins and ion channels. Phospholipases play
      critical roles in the maintenance of membrane structure and function, thereby
      fundamentally integrating dynamic alterations in myocardial performance with
      membrane composition and dynamics. The major phospholipases in myocardium belong
      to a family of proteins known as calcium-independent phospholipases (iPLA2s). In
      addition to their role in maintaining normal membrane structure and function,
      iPLA2 catalytic activity results in the generation of a variety of lipid second
      messengers that facilitate cellular signaling. Through its multiple effects on
      cardiac myocyte bioenergetics, cellular signaling, and membrane function, the
      iPLA2 family of enzymes is of primary importance in modulating the pathologic
      sequelae of myocardial ischemia, diabetic cardiomyopathy, and remodeling during
      hemodynamic stress. This review will provide a brief overview of myocardial
      iPLA2s and their significance in cardiac pathology and physiology.

PMID- 19390347
TI  - The cardioprotective actions of leptin are lost in the Zucker obese (fa/fa) rat.
AB  - Protection against myocardial ischemia-reperfusion injury, including that induced
      by leptin, involves activation of the reperfusion injury salvage kinase pathway
      and inhibition of the mitochondrial permeability transition pore. In the current
      study, we explored the mechanisms underlying leptin-induced cardioprotection
      further with reference to the leptin receptor (OB-R) and obesity. We examined
      hearts from Wistar and Zucker lean rats that express functional OB-R and Zucker
      obese (fa/fa) rats with nonfunctional OB-R. In Langendorff experiments, leptin
      (10 nM) caused significant reductions in infarct size in hearts from Wistar
      (leptin treated, 32.4% +/- 3.9% vs. control, 53.2% +/- 3.2%, P < 0.01) and Zucker
      lean animals (leptin treated, 25.2% +/- 3.7% vs. control, 53.9% +/- 11.3%, P <
      0.01). By contrast, hearts from (fa/fa) did not exhibit significant decreases in
      infarct size. Leptin increased p44 and p42 phosphorylation in Wistar rat hearts
      by 103.9% (P < 0.05) and 157.3% (P < 0.001), respectively, and by 97.0% (P <
      0.05) and 158.1% (P < 0.05) in hearts from Zucker lean rats. Akt/serine-473
      phosphorylation was increased in Wistar hearts by 96.7% (P < 0.05), whereas
      Akt/threonine-308 phosphorylation was elevated by 43.9% (P < 0.05) in Zucker lean
      rat hearts. Leptin did not influence Akt or p44/42 phosphorylation in (fa/fa)
      animals. On leptin treatment, mitochondrial permeability transition pore opening
      was delayed by 43% (P < 0.01) and 30.9% (P < 0.01), respectively, in
      cardiomyocytes from Wistar and Zucker lean rat hearts but not in cardiomyocytes
      from (fa/fa). This study provides the first evidence that myocardial sensitivity
      to the tissue preserving actions of leptin is influenced by adiposity and OB-R
      status.

PMID- 19390349
TI  - The consensus statement on the definition of orthostatic hypotension: a revisit
      after 13 years.

PMID- 19390350
TI  - Are isolated populations better for studying genes that predispose to
      hypertension?

PMID- 19390351
TI  - The aortic pressure wave in aortic stenosis.

PMID- 19390353
TI  - Prognostic value of ventricular repolarization prolongation in resistant
      hypertension: a prospective cohort study.
AB  - OBJECTIVE: The prognostic value of prolonged ventricular repolarization in
      patients with resistant hypertension is unknown. The aim of this prospective
      study was to investigate the usefulness of electrocardiographic QT-interval
      parameters as predictors of cardiovascular morbidity and mortality. METHODS: At
      baseline, 538 resistant hypertensive patients had five QT-interval components
      measured in standard 12-lead ECGs: maximum QRS, QTpeak, QTend, JT and Tpeak-to
      end-interval durations. Primary endpoints were a composite of fatal and nonfatal
      cardiovascular events, all-cause and cardiovascular mortalities. Multiple Cox
      regression assessed the associations between QT-interval parameters and
      subsequent endpoints. RESULTS: After a median follow-up of 4.8 years, 69 (12.8%)
      patients died, 46 from cardiovascular causes, and 107 (19.9%) fatal or nonfatal
      cardiovascular events occurred. After adjustment for several traditional risk
      factors, including 24-h ambulatory systolic blood pressure, an increment of 1 SD
      (35 ms) in QTcend-interval was associated with hazard ratios of 1.38 (1.15-1.67),
      1.51 (1.16-1.98) and 1.30 (1.03-1.64), respectively, for the composite endpoint,
      cardiovascular mortality and all-cause mortality. Further adjustment for left
      ventricular hypertrophy attenuated the relative risks, but they remained
      significant for cardiovascular mortality (1.45, 1.07-1.97) and for the composite
      endpoint (1.35, 1.11-1.66). After full adjustment, a prolonged QTcend-interval (>
      or =460 ms) conferred a 1.7-fold (1.1-2.6) higher risk of having a future fatal
      or nonfatal cardiovascular event. No other QT-interval component added further
      prognostic information to QTcend-interval duration. CONCLUSIONS: Prolonged
      ventricular repolarization is a risk marker for cardiovascular morbidity and
      mortality in patients with resistant hypertension, over and beyond traditional
      cardiovascular risk factors, including ambulatory blood pressure and left
      ventricular hypertrophy.

PMID- 19390355
TI  - Arterial path length measurements required for the pulse wave velocity.

PMID- 19390356
TI  - A comprehensive analysis with minimum 1-year follow-up of vertically unstable
      transforaminal sacral fractures treated with triangular osteosynthesis.
AB  - PURPOSE: To analyze the radiographic, clinical, and functional results of
      triangular osteosynthesis constructs for the treatment of vertically unstable
      comminuted transforaminal sacral fractures. SETTING: Level I trauma center.
      METHODS: During a 3-year period (July 1, 2003 to June 30, 2006), 58 patients with
      vertically unstable pelvic injuries were treated with triangular osteosynthesis
      fixation by a single surgeon at a single institution. Patients were followed-up
      prospectively as a single cohort, with institutional review board approval.
      Inclusion criteria for this study were skeletally mature patients with a
      vertically unstable pelvic ring injury associated with a comminuted
      transforaminal sacral fracture. Minimum follow-up, both clinically and
      radiographically, was 1 year. Computed tomography scan was performed on all
      patients at 6 months to assess healing of the fracture. If the fracture healed,
      the fixation was removed. Functional outcome was assessed using the Short Form
      36, version 2, and short version of Musculoskeletal Functional Assessment
      questionnaires at 6 months (before fixation removal) and 12 months. RESULTS:
      Forty of 58 patients with an average age of 39 years were available for a minimum
      of 1-year follow-up. Wound complications requiring surgical debridement occurred
      in 5 patients (13%), all of whom had severe soft tissue wounds with internal
      degloving. Two patients required removal of infected fixation. Iatrogenic L5
      nerve injury occurred in 5 patients (13%). Ten patients (25%) had a delayed union
      on computed tomography scans, and 3 patients had a nonunion as a result of
      residual fracture gap and incomplete reduction. Six patients (15%) were found to
      have pronounced tilting of the L5 vertebral body (scoliosis) and distraction of
      the L5/S1 facet joint ipsilateral to the fixation. This did not correct with
      removal of the fixation. Failure of the triangular osteosynthesis construct
      resulting in malunion occurred in 2 patients (5%). All but 2 patients (95%)
      complained of painful and prominent implants. Functional outcome scoring showed
      that patients continued to function below the population mean at 1 year but
      continued to improve, particularly with function and daily activity. Ninety-seven
      percent of patients returned to some form of work or schooling. CONCLUSIONS:
      Triangular osteosynthesis fixation is a reliable form of fixation that allows
      early full weight-bearing at 6 weeks while preventing loss of reduction in
      comminuted vertical shear transforaminal sacral fractures. For this study group,
      operative reduction was maintained until healing in 95% of patients. However, the
      1-year follow-up shows a substantial rate of potential technical problems and
      complications. Of primary concern were the asymmetric L5 tilting with L5-S1 facet
      joint distraction and the need for a second surgery in all patients to remove
      painful fixation. Iatrogenic nerve injury occurred in 5 patients (13%) and is
      thought to arise secondary to fracture manipulation and reduction. We recommend
      selective use of this technique for comminuted transforaminal sacral fractures in
      situations only where reliable iliosacral or trans-sacral screw fixation is not
      obtainable.

PMID- 19390358
TI  - Emergent management of APC-2 pelvic ring injuries with an anteriorly placed C
      clamp.
AB  - OBJECTIVE: Can anteriorly placed pelvic C-clamps be used successfully in the
      emergent management of APC-2 pelvic fractures? DESIGN: Prospective cohort.
      SETTING: Level 1 trauma center. PATIENTS: A single-surgeon series of 24 patients
      with an anteroposterior compression type 2 pelvic fracture. INTERVENTION:
      Application of an anteriorly placed pelvic C-clamp within 2 hours of
      presentation. MAIN OUTCOME MEASUREMENTS: Response to hypotension, complications
      related to pin placement, application time, and symphyseal reduction measured on
      anteroposterior radiograph. RESULTS: Twenty-four patients with a mean age of 29
      years (14-58 years) had an APC-2 pelvic fracture diagnosed by an anteroposterior
      radiograph of the pelvis on presentation. All patients were emergently managed
      with an anteriorly placed C-clamp applied in the emergency room (10), angiography
      suite (9), or operating room (5). Eleven patients presented with hypotension
      (systolic blood pressure <90 mm Hg) and had an average elevation of their blood
      pressure of 23 mm Hg (10-44 mm Hg). The symphyseal separation was reduced from a
      mean of 4.5 cm (3-9 cm) to <2 cm in all cases and to <1 cm in 21 of 24 cases.
      Complications included 1 misdiagnosis of an APC-3 injury and 2 cases in which the
      clamp became dislodged when the patients were rolled in the intensive care unit.
      Thirteen patients required laparotomy or angiography for further management after
      the C-clamp was applied. The C-clamp was easily draped out of the field for both
      procedures. CONCLUSIONS: The pelvic C-clamp can be placed anteriorly as a part of
      the early management of APC-2 pelvic fractures with a short application time in a
      variety of patient care areas.

PMID- 19390359
TI  - Skeletal deformity after anterior external fixation of the pelvis.
AB  - OBJECTIVE: To study the deformity of acutely injured unstable pelves before and
      after emergent application of an anterior external fixator. DESIGN:
      Retrospective. SETTING: Large pelvic fracture referral practice. PATIENTS: Eleven
      of 151 patients referred to our institution after emergent application of an
      external fixator by the referring orthopaedist before transfer who were
      hemodynamically unstable and had a mechanically unstable pelvic injury with pre
      external fixator radiographs and post-external fixator radiographs adequate to
      determine pelvic deformity. MAIN OUTCOME MEASUREMENTS: We reviewed all available
      radiographs both before and after placement of the external fixator (the anterior
      posterior, inlet, outlet, and computed tomography), determining whether the
      external fixator improved or worsened the deformity. RESULTS: Although many
      deformities existed, we found that application of an anterior frame consistently
      worsened this deformity. Seven of the 11 patients (64%) had worsening of the
      posterior cephalad translation or posterior diastasis despite apparent
      improvement anteriorly on the anterior-posterior radiograph. "External fixator
      deformity," defined as increased flexion and/or internal rotation of the
      hemipelvis, also occurred in 8 of 11 patients (73%). After placement of the
      external fixator, all patients displayed greater than 1 cm of either posterior
      cephalad translation or posterior diastasis (average 3.4 cm, range 1.3-4.6 cm).
      CONCLUSIONS: Due to the forces placed on the pelvis during application of an
      anterior external fixator by the surgeon, an external fixator deformity may occur
      (flexed and internally rotated hemipelvis). Furthermore, most patients had an
      increase in posterior cephalad translation or posterior diastasis with placement
      of an external fixator. The surgeon should be aware of the potential of
      increasing the pelvic deformity when applying an emergent anterior external
      fixator.

PMID- 19390360
TI  - The upper sacral nerve root tunnel: an anatomic and clinical study.
AB  - OBJECTIVES: To radiographically demonstrate the upper sacral nerve root tunnel
      (USNRT) in both cadaveric specimens and a clinical cohort and to quantify its
      clinical relevance. SETTING: Level 1 trauma center and anatomy laboratory.
      PATIENTS AND PARTICIPANTS: Eleven cadaveric pelves and 23 consecutive patients
      who underwent fluoroscopically assisted iliosacral screw insertions.
      INTERVENTIONS: Cadaveric pelves were fluoroscopically imaged using standard
      pelvic inlet, outlet, and true lateral sacral views. The course of the USNRT
      pathway was identified. Then, these tunnels were filled completely with a
      semisolid radio-opaque agent. The specimens were reimaged after the contrast
      injection. Clinically, 23 consecutive patients with unstable posterior pelvic
      ring disruptions were treated using fluoroscopically assisted percutaneous
      iliosacral screws based on these predictable radiographic landmarks. A total of
      44 iliosacral screws were inserted. MAIN OUTCOME MEASUREMENTS: For the cadaveric
      portion, the images with contrast were used to identify the USNRTs. For the
      clinical study, tunnel visualization was determined on all views
      intraoperatively. Screw placement was documented by postoperative pelvic plain
      radiographs and computed tomography scan. RESULTS: In the cadaveric specimens,
      the contrast agent consistently demonstrated the USNRTs on all 3 pelvic
      radiographic views. In the clinical series, the USNRTs were well visualized on
      the pelvic outlet image in all 23 patients (100%). Using the inlet image, the
      USNRTs were visualized in only 5 of 23 patients (21%). On the true lateral sacral
      views, the USNRTs were seen in 21 of 23 patients (91%). Using these USNRT
      radiographic landmarks, no iliosacral screw was extraosseous. CONCLUSIONS: The
      USNRTs have a consistent radiographic appearance that is best seen on the pelvic
      outlet and true lateral sacral views, but their course is best understood when
      seen on all 3 views. Awareness and understanding of the USNRT, its course, and
      its radiographic landmarks allow the surgeon to avoid tunnel intrusion by an
      iliosacral screw.

PMID- 19390361
TI  - Efficacy of intraoperative red blood cell salvage and autotransfusion in the
      treatment of acetabular fractures.
AB  - OBJECTIVES: To determine if cell saver (CS) use in patients with acetabular
      fractures reduces the volume or rate of allogeneic blood transfused
      intraoperatively and postoperatively and if this translated to a decrease in
      blood-related charges to the patient. DESIGN: Retrospective review. SETTING:
      Level 1 trauma center. PATIENTS: One hundred eighty-six patients with operatively
      treated acetabular fractures. INTERVENTION: All patients underwent open reduction
      internal fixation of their acetabular fracture. The decision to use CS was at the
      surgeon's discretion. MAIN OUTCOME MEASUREMENTS: The volume and rate of
      intraoperative and postoperative allogeneic blood transfused and blood-related
      charges were evaluated. RESULTS: CS was used in 60 cases (32%), and the average
      volume of blood autotransfused was 345 mL. No differences were observed in the
      rates (58.3% vs 48%, P = 0.1883) or the mean volumes (770 vs 518 mL, P = 0.0537)
      of intraoperative and postoperative allogeneic blood transfusions between the CS
      and the non-CS groups. Total blood-related charges in the CS group were
      significantly higher than that in the nonCS group ($1958 vs $694, P < 0.0001).
      Subanalyses based on fracture pattern, injury severity score, body mass index,
      days to surgery, and estimated blood loss were performed. In each subanalyses, no
      differences were observed in intraoperative and postoperative transfusion rates
      and volumes, and total blood-related charges were higher in the CS groups.
      CONCLUSIONS: In the routine use of CS in acetabular surgery, there was no
      reduction in the volume or rate of allogeneic blood transfused intraoperatively
      or postoperatively. However, blood-related charges were significantly increased.

PMID- 19390362
TI  - An analysis of gait changes and functional outcome in patients surgically treated
      for displaced acetabular fractures.
AB  - OBJECTIVES: To determine the relationship between gait, muscle strength, and
      functional outcome in patients who underwent Open Reduction Internal Fixation
      (ORIF) of a displaced acetabular fracture using an anterior ilioinguinal approach
      and to compare gait and functional outcome in patients who have undergone ORIF
      via an anterior approach with a similar group of patients who have undergone ORIF
      of a displaced acetabular fracture via a posterior approach and a group of able
      bodied cohorts and to investigate relationships between gait, strength, and
      functional outcome within the entire group of patients. DESIGN: Case series.
      SETTING: University Medical Center. PATIENTS: Thirty patients were studied, each
      with an isolated displaced acetabular fracture who were surgically treated; 15
      patients were treated using an anterior ilioinguinal approach, and 15 were
      treated using a posterior Kocher-Langenbeck approach. MAIN OUTCOME MEASURES:
      Primary outcome measures included gait analysis (speed and kinematics), hip
      muscle strength, and functional outcome as assessed with the Musculoskeletal
      Function Assessment (MFA) questionnaire. RESULTS: Several of the limb kinematics
      for the affected and the unaffected limbs was different when patients treated by
      an anterior surgical approach were compared with those treated from a posterior
      approach and able-bodied cohorts. Maximum ankle dorsiflexion was greater in the
      unaffected limb of the anterior group versus the posterior approach group but was
      equal to the able-bodied cohorts (AB). Both the affected and the unaffected limbs
      of the anterior group had larger angles for knee flexion at the time of initial
      contact compared with the posterior group and AB. Both limbs of the anterior
      group had significantly more knee flexion and less hip rotation than the
      posterior group but not from AB. There were no differences in trunk inclination
      between the surgical groups, but the combined group had greater inclination
      compared with AB. Average MFA score was 17 +/- 12 (range, 0-47) for the anterior
      group and 22 +/- 17 (range, 0-57) for the posterior group, respectively. MFA
      scores did not differ significantly based on surgical approach, fracture pattern,
      or sex. When gait was compared with MFA scores, an inverse relationship was
      discovered for the group as a whole. That is, worsening function (increased MFA)
      correlated with decreased kinematics and stride length. Additionally, greater hip
      strength was associated with additional hip rotation and increased gait speed. A
      multivariate regression analysis indicated that both hip rotation (which was
      associated with hip strength) and hip adductor work strength were important
      predictors of final MFA scores. CONCLUSIONS: Detailed gait analysis and
      functional outcome determination indicate that patients treated surgically for a
      displaced acetabular fracture, either via an anterior or posterior approach, have
      alterations in their gait, muscle strength, and functional outcome. Maximizing
      hip muscle strength may improve gait, and improvement in hip muscle strength and
      gait is likely to improve functional outcome as measured by the MFA. Finally,
      because both surgical approaches seem to produce the same gait outcomes, it
      suggests that gait changes after injury and treatment are related to factors
      other than surgical approach.

PMID- 19390363
TI  - Technical aspects and recommended treatment algorithms in triangular
      osteosynthesis and spinopelvic fixation for vertical shear transforaminal sacral
      fractures.
AB  - Vertically unstable pelvic ring injuries associated with comminuted
      transforaminal sacral fractures present a special problem to the treating surgeon
      in applying stable fixation for maintaining reduction. Triangular osteosynthesis
      and spinal-pelvic constructs are relatively new techniques used to avoid loss of
      reduction for treating these difficult fractures, and the last decade has seen a
      marked increase in the use of these techniques. This article aims to describe the
      indications and technical aspects in the use of spinal-pelvic constructs for
      vertical shear sacral fractures such that they can be applied to better help the
      patients with these injuries.

PMID- 19390364
TI  - Internal rotation and taping of the lower extremities for closed pelvic
      reduction.
AB  - External rotation of the disrupted hemipelvis is a common deformity after pelvic
      ring trauma, especially in anteroposterior compression injury patterns. This
      displacement is associated with significant pelvic hemorrhage. Emergent closed
      reduction techniques are necessary to diminish the potential pelvic volume,
      provide temporary stability, and allow tamponade with clot formation.
      Circumferential pelvic antishock sheeting is effective but may be cumbersome,
      especially in patients with truncal obesity. In such scenarios, circumferential
      pelvic area sheeting does not always achieve a complete reduction. We present a
      technique of internal rotation and taping of the lower extremities as an
      alternative or supplemental pelvic closed reduction method.

PMID- 19390365
TI  - The subcristal pelvic external fixator: technique, results, and rationale.
AB  - We report a new technique for pelvic external fixation that we have developed as
      an alternative to the anterosuperior (Slatis) and the anteroinferior (supra
      acetabular) type pelvic external fixator configurations. The method principally
      differs from the other techniques by virtue of the subcristal positioning of the
      pins and offers advantages in terms of easier pin placement, less skin
      irritation, less pin tract infection and loosening, and less interference with
      hip flexion, while allowing dressing, sitting, and walking. Between 1992 and
      2006, we successfully used subcristal pelvic external fixators as the definitive
      fixation device for 20 patients with pelvic ring disruptions. The only
      complications encountered were superficial pin tract infections in 4 patients
      (20%) who were successfully treated with wound care and antibiotics.

PMID- 19390366
TI  - A modified anterior exposure to the acetabulum for treatment of difficult
      anterior acetabular fractures.
AB  - Many approaches to the acetabulum have been described for the treatment of
      displaced acetabular fractures. However, the treatment of complex anterior column
      fractures remains difficult. Commonly used approaches allow access to the
      internal cortical surface of the anterior column or a limited view of the outer
      cortical surface of the anterior column. We present a modification of a
      traditional Smith-Peterson approach with osteotomies for extensile exposure to
      the anterior column of the acetabulum.

PMID- 19390367
TI  - A systematic review of thromboprophylaxis for pelvic and acetabular fractures.
AB  - OBJECTIVES: Pelvic and acetabular fractures have been identified as risk factors
      for deep venous thrombosis (DVT) and thromboembolic complications. A systematic
      review was performed to evaluate the effectiveness of thromboprophylactic
      strategies to prevent DVT or pulmonary embolism (PE) after pelvic or acetabular
      fractures. DATA SOURCES: Relevant articles were identified by searching MEDLINE,
      MEDLINE In Process & Other Non-indexed Citations, EMBASE, CENTRAL, and the
      Cochrane Database of Systematic Reviews. All languages and years indexed were
      searched. STUDY SELECTION: Manuscripts were included if (1) the study included an
      intervention or strategy aimed at preventing thromboembolic disease, (2) the
      subjects in the study had suffered a pelvic or acetabular fracture, and (3) the
      primary outcome of the study was DVT or PE. DATA EXTRACTION: The intervention,
      sample size, DVT, and/or PE incidence, and method of diagnosis were recorded for
      each study. DATA SYNTHESIS: Eleven studies with 1760 subjects were included.
      Included studies were grouped into 5 types of interventions: mechanical
      compression devices, inferior vena cava filters, low-molecular weight heparins,
      ultrasound screening, and magnetic resonance venography screening. Most studies
      were observational designs with minimal control data for comparison. Quantitative
      pooling was not possible based on significant study heterogeneity. CONCLUSIONS:
      Although several strategies have been used to prevent thromboembolism in pelvic
      and acetabular fracture patients, our results suggest that clinicians have
      limited data to guide their prophylactic decisions. Well-designed clinical trials
      to prevent and detect venous thromboembolism in pelvic and acetabular trauma are
      still needed.

PMID- 19390368
TI  - Introduction: Biology and new technical trends in intramedullary nailing of the
      femur.

PMID- 19390369
TI  - Intramedullary nailing of the femur: current concepts concerning reaming.
AB  - Intramedullary fixation has advanced to the standard of care for fractures of the
      femoral shaft. Current controversies center on whether to prepare the
      intramedullary canal by reaming, particularly in certain subsets of patients. As
      understanding of the local and systemic effects of reaming deepens, there is a
      role for maximizing the benefits of intramedullary preparation before nail
      fixation, while attempting to minimize the major disadvantages of this technique.
      Several treatment strategies have emerged to address the downsides of
      intramedullary reaming. The purpose of this review is to discuss the history and
      current knowledge of intramedullary reaming with respect to problems associated
      with its use and the evolution of treatment modalities and their clinical
      applicability for orthopaedic trauma care.

PMID- 19390370
TI  - Intramedullary nail fracture compression techniques: when and how to do it?
AB  - Fracture compression can be achieved in many ways intraoperatively using either
      screws in compression plates, compression devices, or using intramedullary nails.
      The use of locked intramedullary nails combines the advantages of indirect
      fracture fixation and compression with minimal soft tissue disruption. This
      article describes the technique, advantages, and limitations of the use of
      intramedullary nails for compression across fractures, nonunions, and joint
      arthrodeses.

PMID- 19390371
TI  - Percutaneous/minimally invasive techniques in treatment of femoral shaft
      fractures with an intramedullary nail.
AB  - Intramedullary nailing of the femur is often the treatment of choice in isolated
      fractures of the femoral shaft. Some surgeons are reticent to use intramedullary
      nailing for proximal and distal femoral fractures. However, indications for
      femoral nailing can be appropriately extended to highly comminuted fractures as
      well as distal and proximal fractures when the correct technique and reduction
      maneuvers are utilized. Implementation of these techniques will also respect the
      critical soft tissue envelope that is so important in fracture healing. Deforming
      forces of the muscles of the hip, knee and thigh are neutralized with reduction
      tools applied percutaneously, blocking screws and Schanz pins. Mastery of these
      techniques and appropriate reduction are incumbent on the orthopaedic surgeon
      treating femoral shaft fractures.

PMID- 19390372
TI  - Nailing of proximal and distal fractures of the femur: limitations and
      techniques.
AB  - Over the last 15 years, a continual evolution of nail design and techniques has
      made nailing at the extremes of the femur more commonplace. This evolution has
      yielded a better understanding and ability to control fractures of the metaphysis
      and, in the distal femur, even intra-articular fractures. With understanding of
      common pitfalls and reduction techniques, uneventful healing with anatomic
      alignment, rotation, and length can be achieved with nails at both far proximal
      and far distal fractures of the femur.

PMID- 19390373
TI  - Indications for antibiotic cement nails.
AB  - This article focuses on the surgical indications and techniques of antibiotic
      nailing of the femur. Spanning external fixation is an essential component of
      damage control orthopaedics. Fractures of the femur with significant soft tissue
      injury also often require prolonged external fixation, which increases the risk
      of infection. Antibiotic nails can sterilize the medullary canal contaminated by
      external fixator pins and prophylax against nosocomial infection, while the pin
      tracts heal to prepare the canal environment for a future staged metal nailing.
      Antibiotic nails may also be used as a bridge to definitive metallic
      intramedullary nailing after spanning external fixation in patients with multiple
      injuries or mangled limbs.

PMID- 19390374
TI  - Advances in the establishment of defined mouse models for the study of fracture
      healing and bone regeneration.
AB  - The availability of a broad spectrum of antibodies and gene-targeted animals
      caused an increasing interest in mouse models for the study of molecular
      mechanisms of fracture healing and bone regeneration. In most murine fracture
      models, the tibia or the femur is fractured using a 3-point bending device
      (closed models) or is osteotomized using an open surgical approach (open models).
      For fracture studies in mice, the tibia has to be considered less appropriate
      compared with the femur because the stabilization of the fracture is more
      difficult due to its triangular, distally declining caliber and its bowed
      longitudinal axis. Biomechanical factors critically influence the bone healing
      process. Thus, the use of stable osteosynthesis techniques is also of interest in
      murine fracture models. To achieve stable fixation, several biomechanically
      standardized implants have recently been introduced, including a locking nail and
      an intramedullary compression screw. Other implants, such as a pin-clip, an
      external fixator, and a locking plate, additionally allow the stabilization of
      fractures with distinct gap sizes. This enables the study of healing of critical
      size defects and nonunions. The use of these implants further allows a rigid
      fixation of fractures in bridle bones, which is essential for fracture studies in
      animals suffering from metabolic bone diseases like osteoporosis. In general, the
      analysis of bone healing in these models includes different imaging techniques
      and histologic, immunohistochemical, biomechanical, and molecular methods. To
      evaluate the impact of different osteosynthesis techniques on physical activity
      and rehabilitation, gait analysis may additionally be performed. By this, the
      gait of the animals can be visualized and quantitatively analyzed using modified
      running wheels and dynamic high-resolution radiography systems. Taken together, a
      variety of different murine femur fracture models have become available,
      providing defined biomechanical conditions for fracture research. The use of
      these mouse models may now allow studying the influence of fracture stabilization
      techniques on molecular mechanisms of bone healing.

PMID- 19390376
TI  - Intraoperative reduction techniques for difficult femoral fractures.
AB  - Successful intramedullary nailing of difficult femoral fractures is predicated on
      achieving and maintaining reduction before reaming and implant insertion. Closed
      and percutaneous strategies are emphasized which preserve fracture biology and
      encourage primary union. However, open techniques are sometimes necessary to
      avoid postoperative deformity.

PMID- 19390375
TI  - Is there a standard rehabilitation protocol after femoral intramedullary nailing?
AB  - INTRODUCTION: The purpose of this article was to describe the impairments and
      functional deficits associated with femoral shaft fractures treated with an
      intramedullary (IM) nail and to illustrate an evaluation-based rehabilitation
      program designed to target these functional deficits. LITERATURE REVIEW: The
      current literature describing management of diaphyseal femur fractures is replete
      with evidence regarding surgical management and optimal bone healing. However, a
      dearth exists with respect to postoperative rehabilitation recommendations,
      targeting the impairments that often limit return to activity. Current literature
      suggests that residual impairments after IM rod fixation of a femoral shaft
      fracture include hip abduction weakness, knee extensor weakness, anterior knee
      pain, and gait abnormalities. Any combination of these impairments can
      potentially limit the ability of a patient to return to prior levels of function.
      A rehabilitation program designed to target these impairments provides the best
      opportunity for a favorable outcome. REHABILITATION PROTOCOL: An evaluation-based
      rehabilitation protocol designed to target known impairments after a femoral
      shaft fracture is presented. Progression through the program is dependent on
      successful attainment of baseline goals. These goals address weight bearing (WB)
      status, knee effusion, quadriceps control, and hip abduction strength. The
      program is a dynamic incorporation of interventions designed to target these
      known impairments. CONCLUSIONS: An evaluation-based rehabilitation protocol for
      femur fractures treated with an IM nail can facilitate restoration of function in
      a predictable manner and should be considered as a standard for patients with
      these injuries.

PMID- 19390390
TI  - NPs: The cornerstone of healthy patients.

PMID- 19390391
TI  - Getting the red out: primary angle-closure glaucoma.

PMID- 19390392
TI  - Is low back pain getting on your nerves?

PMID- 19390394
TI  - Guide to care for patients. Low back pain.

PMID- 19390395
TI  - Common herb-drug interactions: what you should know.

PMID- 19390396
TI  - The heart of the matter: reducing CVD risk.

PMID- 19390397
TI  - Evaluation and management of genitourinary emergencies.

PMID- 19390399
TI  - Diagnosis and management of HPV-related anal dysplasia.

PMID- 19390402
TI  - Acute pancreatitis: a historical perspective.
AB  - Among the various pancreatic disorders, the pace of scientific discovery in acute
      pancreatitis has been particularly slow. The objective of this paper was to
      briefly review the history of scientific discovery of the clinical features,
      pathophysiology, and treatment of acute pancreatitis. A clinical description of
      acute pancreatitis was first presented in 1652 by the Dutch anatomist Nicholas
      Tulp, and despite the nearly 350 years that have passed, there continue to be
      many unanswered questions. In the late 19th and early 20th century, Reginald
      Fitz, Nicholas Senn, Eugene Opie, and others made seminal contributions that
      continue to influence our present understanding of acute pancreatitis. Despite
      remarkable progress in the past 6 decades, our ability to accurately diagnose and
      estimate the severity of acute pancreatitis remains limited. History provides
      multiple examples of empiric remedies and surgical interventions based on the
      prevailing theories and opinions of the scientific luminaries du jour, and
      indeed, after 3 centuries of inquiry, the most effective interventions for acute
      pancreatitis are purely supportive in nature and not specific to the pancreas.
      However, the perseverance of successive generations of the finest scientific
      minds provides hope that we will unravel the many mysteries of this enigmatic
      gland.

PMID- 19390403
TI  - Agenesis of the dorsal pancreas and its association with pancreatic tumors.
AB  - Morphogenesis of the pancreas is a complex process; nevertheless, congenital
      anomalies are rare. At embryogenesis, the pancreas develops from the endoderm
      lined dorsal and ventral buds of the duodenum. The ventral bud gives rise to the
      lower head and uncinate process of the pancreas; whereas, the dorsal bud gives
      rise to the upper head, isthmus, body, and tail of the pancreas. Rarely,
      developmental failure of the dorsal pancreatic bud at embryogenesis results in
      the agenesis of the dorsal pancreas--neck, body, and tail. Even rarer is the
      association of pancreatic tumors with agenesis of the dorsal pancreas. In
      addition to citing our case, we provide a comprehensive review on agenesis of the
      dorsal pancreas and its association with pancreatic tumors.

PMID- 19390404
TI  - The role of leptin in idiopathic chronic pancreatitis?

PMID- 19390406
TI  - Adipocytokine levels in chronic pancreatitis.

PMID- 19390407
TI  - Comment on "Lw fecal elastase 1 levels do not indicate exocrine pancreatic
      insufficiency in type-1 diabetes mellitus (pancreas. 2008;36:274-278)".

PMID- 19390410
TI  - Pancreaticoduodenectomy in India: how far are we from centralization?

PMID- 19390411
TI  - Endoscopic ultrasound-guided aspiration and oral antibiotic therapy as definitive
      treatment of an asymptomatic pancreatic abscess.

PMID- 19390412
TI  - Autoimmune pancreatitis, sclerosing cholangitis, liver inflammatory pseudotumors,
      retroperitoneal fibrosis, lymphadenopathy, and sialoadenitis in a single patient:
      a multifaceted expression of a hitherto unrecognized systemic autoimmune
      syndrome?

PMID- 19390413
TI  - Acute pancreatitis associated with the measles virus: case report and review of
      literature data.

PMID- 19390418
TI  - Anal human papillomavirus infection is associated with HIV acquisition in men who
      have sex with men.
AB  - OBJECTIVE: Human papillomavirus (HPV) is a common sexually transmitted agent that
      causes anogenital cancer and precancer lesions that have an inflammatory
      infiltrate, may be friable and bleed. Our aim was to determine the association
      between anal HPV infection and HIV acquisition. DESIGN: A prospective cohort
      study. METHODS: We recruited 1409 HIV-negative men who have sex with men from a
      community-based setting in Boston, Denver, New York and San Francisco. We used
      Cox proportional hazards regression modeling and assessed the independent
      association of HPV infection with the rate of acquisition of HIV infection.
      RESULTS: Of 1409 participants contributing 4375 person-years of follow-up, 51 HIV
      seroconverted. The median number of HPV types in HPV-infected HIV-seroconverters
      was 2 (interquartile range 1-3) at the time of HIV seroconversion. After
      adjustment for sexual activity, substance use, occurrence of other sexually
      transmitted infections and demographic variables, there was evidence (P = 0.002)
      for the effect of infection with at least two HPV types (hazard ratio 3.5, 95%
      confidence interval 1.2-10.6) in HIV seroconversion. CONCLUSION: Anal HPV
      infection is independently associated with HIV acquisition. Studies that
      incorporate high-resolution anoscopy to more accurately identify HPV-associated
      disease are needed to determine the relationship between HPV-associated disease
      and HIV seroconversion.

PMID- 19390417
TI  - Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV
      associated atherosclerosis.
AB  - OBJECTIVE: HIV-seropositive patients are at higher risk for atherosclerosis than
      HIV-seronegative persons. This has been variably attributed to antiretroviral
      drug toxicity, immunodeficiency, and/or HIV-associated inflammation. To evaluate
      the contributions of these factors to HIV-associated atherosclerosis, we assessed
      carotid artery intima-media thickness in a diverse cohort of HIV-seronegative and
      seropositive adults, including a unique group of HIV-infected patients who were
      untreated, had undetectable viral loads, and had preserved CD4 T-cell counts (HIV
      controllers). METHODS AND RESULTS: Carotid intima-media thickness was measured in
      494 participants, including 33 HIV controllers and 93 HIV-seronegative controls.
      HIV controllers had higher intima-media thickness than seronegative controls even
      after adjustment for traditional risk factors (P = 0.003). Intima-media thickness
      in controllers was similar to antiretroviral-untreated patients with detectable
      viremia. Across all participants, intima-media thickness was strongly associated
      with the presence of HIV disease rather than viral load or CD4 T-cell count. C
      reactive protein was higher in HIV controllers than HIV-seronegative persons.
      Antiretroviral drug exposure was also associated with higher intima-media
      thickness. CONCLUSIONS: Increased atherosclerosis with HIV infection can occur in
      the absence of antiretroviral therapy, detectable viremia, or overt
      immunodeficiency. Chronic inflammation - which is higher in controllers than in
      HIV-uninfected persons - may account for early atherosclerosis in these patients.

PMID- 19390420
TI  - Comparison of gene expression profiles in tubulocystic carcinoma and collecting
      duct carcinoma of the kidney.
AB  - The relationship between tubulocystic carcinoma and collecting duct carcinoma of
      the kidney remains controversial. Some experts are of the opinion that the tumors
      are related, considering tubulocystic carcinoma to be synonymous with low-grade
      collecting duct carcinoma. However, others maintain that the 2 are distinct,
      unrelated entities on the basis of morphologic features and clinical outcome. To
      explore the relationship between tubulocystic carcinoma and collecting duct
      carcinoma, we compared the expression of several gene products at the mRNA level
      in cohorts of each tumor subtype. Seven cases of tubulocystic carcinoma and 8
      cases of collecting duct carcinoma were identified. Total RNA was isolated from
      formalin-fixed paraffin-embedded tissue from each case. Relative expression
      levels of vimentin, alpha methylacyl CoA racemase, E-cadherin, p53, CD10 antigen,
      parvalbumin, cytokeratin 7, and cytokeratin 19 were assessed by quantitative
      reverse transcription polymerase chain reaction. Tubulocystic carcinoma was
      characterized by relative overexpression of vimentin, p53, and alpha methylacyl
      CoA racemase, compared with collecting duct carcinoma (P<0.05 for each gene, t
      test). In general, tubulocystic carcinoma expressed higher levels of E-cadherin
      and CD10, whereas collecting duct carcinoma expressed higher levels of
      cytokeratin 19; however, these trends did not reach statistical significance in
      this study cohort. Tubulocystic carcinoma and collecting duct carcinoma did not
      express cytokeratin 7 differentially. Case-to-case variability of gene expression
      limited the effectiveness of any one marker to distinguish the tumor types. Our
      study demonstrates that tubulocystic carcinoma and collecting duct carcinoma have
      different expression profiles of selected genes, including vimentin, p53, and
      alpha methylacyl CoA racemase. Further analysis of additional cases, using
      quantitative reverse transcription polymerase chain reaction and
      immunohistochemistry, will be useful to test the reproducibility of these
      findings. In addition, larger studies may establish statistical differences in
      expression of other genes analyzed in this study. Overall, these findings support
      the view that tubulocystic carcinoma and collecting duct carcinoma should be
      considered as 2 distinct entities at the molecular level.

PMID- 19390419
TI  - Functional characteristics of HIV-1 subtype C compatible with increased
      heterosexual transmissibility.
AB  - BACKGROUND: Despite the existence of over 50 subtypes and circulating recombinant
      forms of HIV-1, subtype C dominates the heterosexual pandemic causing
      approximately 56% of all infections. OBJECTIVE: To evaluate whether viral genetic
      factors may contribute to the observed subtype-C predominance. METHODS: Chimeric
      viruses were generated using V1-V3 envelope fragments from a subtype-A/C dually
      infected woman with preferential genital replication of subtype C. Viral
      adaptation, spread and cell fusion ability were evaluated in vitro using
      peripheral blood mononuclear cells and HeLa-CD4-CCR5 cell lines, sequencing and
      cloning. Structural modeling was performed using a crystal structure of gp120-CD4
      X5. Phylogenetic analysis was done using subtype-A, subtype-B and subtype-C
      sequences from blood and cervix of 37 infected women and database sequences.
      RESULTS: We identified two envelope motifs, compact V1-V2 loops and V3-316T,
      which are found at high frequency throughout subtype-C evolution and affect gp120
      interactions with CD4 and CCR5, respectively. When a V1-Delta5 deletion or V3
      A316T was incorporated into subtype A, each increased viral fusion and spread
      several fold in peripheral blood mononuclear cell and cell lines with low CCR5
      expression. Structural modeling suggested the formation of an additional hydrogen
      bond between V3 and CCR5. Moreover, we found preferential selection of HIV with
      316T and/or extremely short V1-V2 loops in cervices of three women infected with
      subtypes A/C, B or C. CONCLUSION: As CD4-CCR5-T cells are key targets for genital
      HIV infection and cervical selection can favor compact V1-V2 loops and 316T,
      which increase viral infectivity, we propose that these conserved subtype-C
      motifs may contribute to transmission and spread of this subtype.

PMID- 19390421
TI  - SALL4 is a novel diagnostic marker for testicular germ cell tumors.
AB  - The diagnosis of testicular germ cell tumors (GCTs) sometimes can be challenging
      without ancillary markers. Here we performed an immunohistochemical study of a
      novel stem cell marker SALL4 in a large series of 110 primary testicular GCTs (65
      pure and 45 mixed) containing the following types of tumors and/or tumor
      components: 50 intratubular germ cell neoplasias (ITGCNs), 62 classic seminomas,
      2 spermatocytic seminomas, 39 embryonal carcinomas (EC), 5 pediatric and 26
      postpubertal yolk sac tumors (YST), 7 pediatric and 25 postpubertal teratomas,
      and 5 choriocarcinomas. We compared SALL4 with OCT4 in all GCTs, and SALL4 to
      alpha-fetoprotein (AFP) and glypican-3 in all YSTs. To test SALL4 specificity, 23
      testicular non-GCTs (10 Leydig cell tumors, 4 Sertoli cell tumors, 3 adenomatoid
      tumors, 3 paratesticular rhabdomyosarcomas, 2 diffuse large B-cell lymphomas, and
      1 rete testis papillary cystadenoma) and 275 nontesticular tumors (158 metastatic
      carcinomas, 12 metastatic melanomas, 11 primary and 2 metastatic mesotheliomas,
      and 72 primary and 20 metastatic sarcomas) were also stained for SALL4. All
      ITGCNs, classic seminomas, and ECs demonstrated strong SALL4 and OCT4 staining in
      more than 90% tumor cells. All 31 YSTs (5 pediatric and 26 postpubertal) showed
      strong positive SALL4 staining in more than 90% tumor cells but had negative OCT4
      staining. Both spermatocytic seminomas showed positive SALL4 staining in 80% to
      95% tumor cells in all 3 types of tumor cells with weak-to-moderate staining
      intensity. Mononucleated trophoblastic cells were variably positive for SALL4
      staining in all 5 choriocarcinomas. Focal SALL4 staining was seen in 4 of 7
      pediatric and 23 of 27 postpubertal teratomas. OCT4 staining was not seen in any
      spermatocytic seminoma, choriocarcinoma, or teratoma. No SALL4 staining was seen
      in all 23 testicular non-GCTs. Of 275 nontesticular tumors, only 10 carcinomas
      and 1 sarcoma showed focal (<25% tumor cells) weak SALL4 staining. The only non
      neoplastic cells within the testis stained with SALL4 were spermatogonia and few
      primary spermatocytes. AFP staining was seen in 29 of 31 YST but it was often
      focal and patchy. Although all 31 YSTs showed glypican-3 staining, 14 (45%) show
      staining in less than 30% tumor cells. Our findings indicate that SALL4 is a
      novel sensitive and relatively specific marker for testicular GCTs. SALL4 is a
      more sensitive marker than AFP and glypican-3 for YST.

PMID- 19390422
TI  - Critical diagnoses in surgical pathology: a retrospective single-institution
      study to monitor guidelines for communication of urgent results.
AB  - Recent attention has shifted toward defining critical values in surgical
      pathology, as used in clinical pathology for urgent laboratory results, which
      require immediate physician notification. The Association of Directors of
      Anatomic and Surgical Pathology recently proposed a schema for critical values in
      surgical pathology, better defined as critical diagnoses (CDs). To this end, our
      department established guidelines defining the timely communication and
      documentation of urgent findings. To monitor policy effectiveness and to refine a
      customized list of CDs, we analyzed reports over two identical 6-month periods in
      2006 and 2007 for the proper documentation and communication of urgent results.
      Of all the general surgical pathology cases examined, slightly more than 3% were
      communicated urgently to the requesting physicians. Approximately 20% of those
      cases fell into one of the recently proposed CD categories, whereas the remaining
      cases had conditions that were not specified by the Association of Directors of
      Anatomic and Surgical Pathology, but nonetheless justified immediate notification
      based on local practice, such as graft-versus-host disease, acute tubulo
      interstitial nephritis, and unsuspected amyloidosis. Consecutive cases from a 4
      day period reviewed in 2006 showed that 23.5% notified cases were not properly
      documented in the final report. However, the compliance rate improved to 100% for
      a similar period in 2007. Our study demonstrates the need for any CD list to be
      customized at a given institution to address all the potential diagnoses
      necessary for patient care and management. It further shows that continuous
      monitoring and education with regard to CDs and timely communication and
      documentation of unexpected surgical pathology findings are important measures
      for optimizing patient safety.

PMID- 19390423
TI  - Epithelioid-cell myofibroblastoma of the breast: expanding the morphologic
      spectrum.
AB  - Myofibroblastoma (MFB) of the breast is an uncommon benign tumor, which exhibits
      a wide variety of cytomorphologic features and architectural patterns.
      Epithelioid-cell MFB is a rare morphologic variant exclusively or predominantly
      (>50%) composed of cells with epithelioid morphology, which can represent a
      potential diagnostic pitfall. This study describes the clinicopathologic features
      of 4 cases of epithelioid-cell MFB, including core biopsy-based morphology in 2
      cases. Characteristic histologic features included the presence of well
      circumscribed margins; epithelioid cells variably admixed with a minority (10% to
      40%) of round, polygonal, and spindle-shaped cells; low mitotic activity (0 to 2
      mitoses/10 high-power fields); and a mild-to-moderate degree of nuclear
      pleomorphism. The following growth patterns were observed: alveolar, single-cell,
      single-file, solid, and fascicular growth patterns. In 1 case, neoplastic cells
      exhibited an unusual cellular arrangement, with the formation of neural-like
      structures resembling small peripheral nerves. All but 1 case contained an
      intratumoral mature fatty component that variably accounted from 10% to 40% of
      the entire tumor. The close admixture of atypical epithelioid cells with
      intratumoral adipocytes imparted a pseudo-infiltrative appearance, particularly
      in 1 case. This study emphasizes that epithelioid-cell MFB may be a diagnostic
      challenge, especially when evaluating needle core biopsies. Immunohistochemistry,
      revealing a variable coexpression of vimentin, desmin, alpha-smooth muscle actin,
      CD34, bcl-2 protein, CD99, CD10, estrogen/progesterone/androgen receptors, is
      crucial in confirming the diagnosis. Awareness of epithelioid-cell MFB is
      important to avoid a misdiagnosis of malignancy.

PMID- 19390424
TI  - Flat epithelial atypia on core needle biopsy: which is the right management?
AB  - The clinical significance and management (surgical excision vs. follow-up) of the
      patients with the diagnosis of flat epithelial atypia (FEA) on core needle biopsy
      (CNB) are actually under discussion. Using standardized criteria and precise
      terminology, we analyzed retrospectively our CNB diagnosis of FEA, dividing
      patients with pure FEA as the most advanced pathologic lesion from patients with
      FEA associated to atypical ductal hyperplasia (FEA+ADH). Both the categories were
      correlated with radiologic data and findings on subsequent surgery. We evaluated
      875 core needle biopsies (11-gauge stereotactic vacuum-assisted procedure),
      performed over a 5-year period. A CNB diagnosis of pure FEA was made in 33/875
      (3.7%) cases; in other 11 (1.2%) cases we observed the coexistence of FEA and
      ADH. Subsequent surgical excisions were available in 20/33 pure FEA and in 10/11
      FEA+ADH: of the 20 patients with pure FEA on CNB, none had either ductal
      carcinoma in situ or invasive carcinoma in their excisional biopsy, whereas 3/10
      (30%) FEA+ADH on CNB showed, at subsequent surgery, more advanced lesions (2
      ductal carcinoma in situ, 1 invasive carcinoma). Our results suggest that
      patients with an 11-gauge vacuum-assisted CNB diagnosis of pure FEA (especially
      if related to a small radiologic target, completely or almost completely removed
      by the needle biopsy procedure) could be spared surgical excision and managed
      with close radiologic follow-up.

PMID- 19390426
TI  - Comment on "lymph nodes after preoperative chemoradiotherapy for rectal
      carcinoma: number, status, and impact on survival".

PMID- 19390427
TI  - Basal cytokeratin and epidermal growth factor receptor expression are not
      predictive of BRCA1 mutation status in women with triple-negative breast cancers.
AB  - BACKGROUND: Over 80% of breast cancers in women with germline BRCA1 mutations are
      estrogen receptor, progesterone receptor, and human epidermal growth factor
      receptor 2-negative ("triple negative") and most of these have a basal-like
      phenotype by expression profiling and immunophenotypic analysis. However, whether
      or not expression of biomarkers characteristic of basal-like breast cancers helps
      to define a subset of women with triple-negative breast cancers who are likely to
      harbor BRCA1 mutations is an unresolved issue. METHODS: We randomly identified
      165 women from the Dana-Farber/Harvard Cancer Center SPORE annotated specimen
      bank with primary invasive, triple-negative breast cancers. Tissue microarrays
      were constructed by obtaining triplicate 0.6 mm cores from available paraffin
      blocks from 130 cases: only unstained slides were available for immunostaining
      from 35 cases. Slides cut from the tissue microarrays and the unstained slides
      were immunostained for estrogen receptor, progesterone receptor, and human
      epidermal growth factor receptor 2 (to confirm triple-negative status) and for
      several markers that have been reported to be useful in defining the basal-like
      phenotype, including basal cytokeratins CK5/6, CK14, and CK17 and epidermal
      growth factor receptor (EGFR). Full sequencing analysis for BRCA1 germline
      mutations was performed on blood specimens from all cases. The final study
      population consisted of 144 cases in which (1) triple-negative status was
      confirmed; (2) there was sufficient material for analysis of basal cytokeratins
      and EGFR; and (3) germline BRCA1 mutation status was known. RESULTS: Among these
      triple-negative breast cancer cases, 97 (67%) expressed one or more basal
      cytokeratins and 102 (71%) showed EGFR expression. Basal cytokeratin expression
      was detected in 65% of the tumor from the 20 BRCA1 mutation carriers and in 68%
      of the cancers from women without mutations (P=NS). EGFR expression was
      identified in a similar proportion of tumors from women with and without BRCA1
      mutations (75% vs. 72%, P=NS). CONCLUSIONS: Basal cytokeratin and EGFR expression
      are both highly prevalent among triple-negative breast cancers. The frequency of
      expression of basal cytokeratins and EGFR was similar in women with and without
      BRCA1 mutations. Therefore, although the expression of basal cytokeratins and/or
      EGFR can be used to identify triple-negative breast cancers that have a basal
      like phenotype, expression of these markers alone is not sufficient to
      distinguish which women with triple-negative breast cancers are likely to harbor
      BRCA1 germline mutations.

PMID- 19390428
TI  - Numismedica: health problems caused by coins.
AB  - Coins occasionally cause health problems. These have a wide range of
      presentations and can affect multiple organ systems. This article presents a
      review of the medical literature addressing health problems caused by coins.
      These problems can be categorized as follows: (1) respiratory manifestations of
      ingested coins, (2) gastrointestinal manifestations of swallowed coins, (3)
      systemic effects of swallowed coins, (4) clinical management of swallowed coins,
      (5) allergic manifestations of coin exposure, and (6) miscellaneous health issues
      related to swallowed coins.

PMID- 19390429
TI  - New therapeutic options in patients prone to hypertension: a focus on direct
      Renin inhibition and aldosterone blockade.
AB  - Certain patient populations have a high prevalence of hypertension, including
      black, elderly, or obese patients; patients with metabolic syndrome, or frank
      diabetes; and patients with chronic kidney disease. Many of these patients
      experience renin-angiotensin-aldosterone system (RAAS) dysregulation, which is
      important because the RAAS plays a pivotal role in the pathogenesis of
      hypertension, cardiovascular disease, and renal dysfunction. Data available
      regarding newer approaches that target the RAAS, including direct renin
      inhibition and aldosterone receptor antagonism, in patients who often have
      hypertension are reviewed. Aliskiren, the first direct renin inhibitor, is
      effective in a number of these patient groups, including those who are black or
      obese or who have metabolic syndrome, renal impairment, or diabetes. In addition,
      in the setting of long-term angiotensin-converting enzyme inhibitor or
      angiotensin receptor blocker therapy, aldosterone receptor antagonists
      (spironolactone and eplerenone) provide another rational therapeutic approach for
      patients whose blood pressure is not controlled by standard therapies.

PMID- 19390430
TI  - A rare case of follicular thyroid carcinoma in a patient with thyrotropin
      secreting pituitary adenoma.
AB  - OBJECTIVE: To report a rare case of a thyrotropin (TSH)-secreting pituitary
      adenoma associated with thyroid carcinoma. METHODS: We report the clinical
      history, imaging studies, and laboratory and pathologic data in a male patient
      affected by TSH-secreting pituitary adenoma and goiter; histologic evaluation
      revealed thyroid carcinoma. RESULTS: A 50-year-old man complained of years of
      palpitations, hypertensive crisis, and excessive nervousness that tended to
      progressively worsen. The basal and dynamic hematologic evaluation showed the
      presence of high free thyroid hormone levels with inappropriate levels of TSH.
      The thyroid morphologic study using Doppler ultrasonography showed a gland of
      increased volume with multiple nodular lesions bilaterally. The nuclear magnetic
      resonance of the pituitary gland described a microadenoma. A total thyroidectomy
      was performed followed by neurosurgical treatment of the pituitary lesion. The
      definitive thyroid histologic examination showed the presence of minimally
      invasive follicular carcinoma of 17 mm diameter. The patient firmly refused
      surgical removal of the pituitary adenoma. He was started on replacement therapy
      with thyroxine. Twelve months later, the hematologic examinations showed normal
      thyroid hormone levels and a TSH of 6.97 uIU/mL. The pituitary nuclear magnetic
      resonance showed a stable lesion without difference in size. CONCLUSION: The
      clinical association between thyroid carcinoma and TSH-producing adenoma is rare,
      with the removal of the pituitary lesion being mandatory. Pituitary surgery, in
      this case, is impossible, showing that TSH-producing microadenoma could seldom
      have an indolent behavior.

PMID- 19390431
TI  - Lupus nephritis.
AB  - Lupus nephritis (LN) is one of the common manifestations of systemic lupus
      erythematosus. Kidney biopsy remains a mainstay of LN diagnosis, which is usually
      prompted by abnormal urinary sediment, proteinuria, or elevated creatinine. New
      International Society of Nephrology/Renal Pathology Society classification of LN
      tends to remove some of the ambiguities of World Health Organization
      classification and results in better categorization of patients. Although
      prognosis of LN has improved with the combined use of cytotoxic and steroid
      therapy, up to 20% of these patients progress to renal failure. Moreover,
      toxicity of the current regimens remains a major concern. Last few decades have
      seen a tremendous progress being made in understanding the pathogenesis of LN,
      but a little has been added to armamentarium against LN, leaving physicians with
      a few choices. Fortunately, with unfolding of molecular processes involved in
      disease pathogenesis, new targets for drug therapy have emerged. Whether these
      medications will prove to be more efficacious and less toxic remains a matter of
      debate and will be answered by several ongoing trials and future studies.

PMID- 19390432
TI  - Two unusual cases of Takotsubo cardiomyopathy presenting with sudden cardiac
      death.
AB  - Takotsubo cardiomyopathy also known as transient ballooning syndrome is
      characterized by reversible left ventricular dysfunction with presentation
      mimicking myocardial infarction. Even though this syndrome has been recognized
      for nearly 2 decades, cases with atypical features are still being reported. We
      describe 2 patients who presented to the hospital after cardiac arrest, which is
      very rare according to previous reports. Although still considered a benign
      condition, transient ballooning syndrome could be responsible for some of the
      undiagnosed sudden cardiac deaths in the community, and it may have a worse
      prognosis than currently recognized. In addition, 1 of our patients also had a
      previously unreported triggering factor, namely sexual intercourse.

PMID- 19390433
TI  - A localizable, biological-based system for the delivery of bioactive IGF-1
      utilizing microencapsulated genetically modified human fibroblasts.
AB  - Insulin-like growth factor 1 (IGF-1) is a potent mitogen and differentiation
      factor with particular relevance to orthopedic tissue engineering. A biologically
      based Ca2+-alginate microcapsule vehicle, utilizing genetically modified primary
      normal human fibroblasts (NHFs), was developed and characterized for localized
      synthesis and delivery of human IGF-1 (hIGF-1). Normal human fibroblasts were
      transfected to overexpress the hIGF-1 gene, leading to cells that expressed 4 ng
      of hIGF-1 per 10(6) cells per 24 hours. Encapsulation within alginate led to a
      six-fold enhancement in the generation and release of hIGF-1 to 22 ng of hIGF-1
      per 10(6) cells per 24 hours. Release was constitutive, predictable, and
      exhibited highly repeatable first-order kinetics with no initial burst. Released
      growth factor was biologically active and exhibited a proliferative effect
      comparable to commercially available recombinant hIGF-1. The magnitude of hIGF-1
      release met the requirements of orthopedic tissue generation, and this approach
      is considered an attractive alternative to other proposed methods of growth
      factor delivery.

PMID- 19390434
TI  - Why do doctors and patients not follow guidelines?
AB  - PURPOSE OF REVIEW: The aim of this review is to evaluate the factors related to
      the doctor and the patient that could make following the guidelines difficult. It
      also underlines the importance of the adherence to guidelines themselves in order
      to ameliorate both the control of healthcare and the patients' quality of life.
      RECENT FINDINGS: Following guidelines not only depend on factors related to
      guidelines themselves, to social-cultural context or to the strategies used to
      spread them: different studies have underlined that the characteristics linked to
      the doctor's and patient's subjectivity are crucial. SUMMARY: Guidelines are
      recommendations regarding clinical behaviour, and their implementation is a
      complex process that is influenced by different factors, related both to the
      characteristics of guidelines themselves and to the social, organizational,
      economic and political context or to implementation strategies. During the last
      few years, different studies and theories have tried to explain the reason why
      doctors and patients do not follow the guidelines. Following the guidelines most
      of all depends on the characteristics linked to the doctor's and patient's
      subjectivity, which can be a real obstacle. Knowledge, attitude, skills,
      experiences, believes and values play a fundamental role both in physician and
      patient. By addressing these issues to physician's and patient's adherence, more
      exhaustive approaches to guidelines development and spread can be applied in
      order to improve care and outcomes.

PMID- 19390435
TI  - Hypersensitivity reactions to food additives.
AB  - PURPOSE OF REVIEW: To provide an updated concise review on food additives adverse
      reactions, diagnosis, and management. RECENT FINDINGS: Despite the common use of
      food additives, their adverse reactions seem to be very rare in the general
      population (0.01-0.23%) but higher in atopic individuals (2-7%). Probably because
      of the difficulty in diagnosis, most of the available information is based on
      case reports or small series. Reported reactions are mostly mild and may affect
      the skin, the gastrointestinal tract, or the airways, and rarely anaphylaxis.
      SUMMARY: Food additives should be suspected as the culprit in patients who report
      a history of reactions to a number of unrelated foods or to a certain food when
      commercially prepared but not when prepared at home. The major problem in dealing
      with reactions to additives is the identification of the offending agent(s).
      Apart from a careful history taking, allergy skin testing or in-vitro testing are
      rarely useful. Trials of elimination and reintroduction may be more helpful. If
      the anticipated reaction is severe, a well designed challenge testing should be
      carried out. Once the offending additive(s) is confirmed, treatment is avoidance.
      Because accidental exposure often happens, patients with a history of severe
      reactions should have self-injectable epinephrine and wear MedicAlert (Turlock,
      California, USA) identification.

PMID- 19390436
TI  - The retinal oxysterol pathway: a unifying hypothesis for the cause of age-related
      macular degeneration.
AB  - PURPOSE OF REVIEW: To summarize recent findings implicating toxic agents
      resulting in photooxidation of cholesterol in the etiology of age-related macular
      degeneration. Understanding the role of these agents and the existing pathways
      for their neutralization may lead to novel therapeutic approaches. RECENT
      FINDINGS: The human eye is now known to produce significant quantities of 7
      ketocholesterol and related substances as a direct result of photoreceptor
      function. These substances are highly toxic to retinal cells and the eye has been
      shown to be unique among human organs in expressing three separate enzymatic
      pathways that neutralize these agents. Drusen are recently shown to contain
      significant accumulations of 7-ketocholesterol, likely as a result of failure of
      these neutralization pathways. In addition to its direct tissue toxicity, which
      may trigger death of retinal pigment epithelium and photoreceptor cells,
      ketocholesterol is a potent attractor of macrophages and induces macrophages to
      express both vascular endothelial growth factor F and metalloproteinases. The
      role of the former in neovascularization is well understood, whereas the latter
      is capable of directly inducing breaks in Bruch's membrane. SUMMARY: The toxic
      role of 7-ketocholesterol and existing pathways for its neutralization may point
      the way to a unified theory that explains the cause of age-related macular
      degeneration and points towards novel therapeutic interventions.

PMID- 19390437
TI  - Comparison of 25, 23 and 20-gauge vitrectomy.
AB  - PURPOSE OF REVIEW: The history and development of 25-gauge and 23-gauge
      vitrectomy are reviewed in this paper and compared with 20-gauge vitrectomy, the
      historical gold standard. Current advantages and disadvantages of each are
      delineated. RECENT FINDINGS: Transconjunctival sutureless vitrectomy continues to
      offer advantages of increased patient comfort decreased operative times and
      improved postoperative astigmatism. These advantages, however, must be weighed
      against the possibility of increased rates of postoperative hypotony and
      endopthalmitis. SUMMARY: Both 25-gauge and 23-gauge instruments continue to
      evolve, and have improved significantly since their introductions. Most cases can
      now be performed using either 25-gauge or 23-gauge techniques with success rates
      comparable to 20-gauge. Despite these advantages, there are still cases where 20
      gauge is appropriate and preferable. Clinical experience, innovations and further
      studies will help dictate the future course of pars plana vitrectomy
      instrumentation.

PMID- 19390438
TI  - Pediatric emergency care in a failing economy.

PMID- 19390439
TI  - Sports-related concussions in pediatrics.
AB  - PURPOSE OF REVIEW: Mild traumatic brain injury (mTBI) accompanied by concussion
      is a common presenting complaint among children presenting to emergency
      departments (EDs). There is wide practice variation regarding diagnosis and
      management of sports-related concussions in children. Our aim is to review the
      most recent evidence and expert recommendations regarding initial diagnosis and
      management of sports-related concussions in children. RECENT FINDINGS: Previous
      classifications and return-to-play guidelines for sports-related concussions in
      children were inadequate and have been abandoned. The most recent
      recommendations, from the Third International Conference on Concussion in Sport
      (CIS), reinforce an individualized evaluation of the athlete's neurocognitive
      functioning, symptoms and balance. They further reinforce a step-wise approach in
      the return-to-play process once neurocognitive function has returned to baseline
      and all symptoms have resolved. The need for a standardized and objective tool to
      aid in the initial evaluation and diagnosis of mTBI in the clinical setting led
      to the development of the Acute Concussion Evaluation (ACE) protocol, which is
      currently being modified for specific use in the ED. Computed tomography (CT) in
      the acute setting is not likely to be useful for children with mTBI. Newer
      functional imaging techniques may prove relevant in the future. SUMMARY: Further
      research on both the incidence of sports-related concussions in children and
      management paradigms is needed. The role of novel imaging modalities in clinical
      assessment also needs to be elucidated. An individualized approach to evaluation
      and management of sports-related concussions is recommended. It should
      incorporate standard symptom assessment, neuropsychological testing and postural
      stability testing.

PMID- 19390440
TI  - Case report: atypical Lemierre's disease secondary to Porphyromonas
      asaccharolytica.
AB  - Lemierre's disease, also known as 'postanginal sepsis', 'necrobacillosis', or
      'internal jugular vein thrombosis', is a rare but serious emerging infection.
      Although Lemierre's disease remains rare, the number of reported cases has risen
      in recent years as more judicious antimicrobial prescribing practices for viral
      upper respiratory tract infections are being employed by primary care
      practitioners, allowing the propagation of bacterial superinfection. The most
      commonly implicated pathogen is Fusobacterium necrophorum, a gram-negative
      anaerobe that resides in the oropharynx and possesses numerous virulence factors
      that promote coagulation and thrombus formation. Here we describe the case of a
      16-year-old male who presented with fever, neck pain, and odynophagia and was
      ultimately diagnosed with an atypical variant of Lemierre's disease secondary to
      Porphyromonas asaccharolytica, a rarely described etiologic pathogen.

PMID- 19390441
TI  - BKB-SIN and ANL predict perceived communication ability in cochlear implant
      users.
AB  - OBJECTIVE: Cochlear implant (CI) users typically report that speech recognition
      becomes substantially more difficult in the presence of background noise. This
      perception is consistent with objective measures of speech recognition showing
      that CI users require more favorable signal-to-noise ratios than normal-hearing
      (NH) listeners to achieve equivalent speech recognition. However, recent research
      in hearing aid users suggests that noise tolerance or the "willingness to listen
      in noise" may also influence perceived communication ability. Therefore, the
      purpose of this study was to evaluate the extent to which speech recognition in
      noise and noise tolerance predict perceived communication ability among adult CI
      users. DESIGN: Twenty adult CI users were evaluated on an objective test of
      speech recognition in noise (Bamford-Kowal-Bench Sentences in Noise [BKB-SIN]
      test) and a measure of noise tolerance (Acceptable Noise Level [ANL] test) and
      completed a self-report measure of communication difficulty (Abbreviated Profile
      of Hearing Aid Benefit [APHAB]). Relationships between BKB-SIN scores, ANL
      scores, and aided APHAB scores for the ease of communication, background noise,
      reverberation, and Global scales were assessed. In addition, BKB-SIN scores and
      ANL scores for the CI users were compared with scores for a control group of 23
      NH listeners. RESULTS: CI users demonstrated substantially poorer BKB-SIN scores
      than NH listeners, as expected; however, their ANL scores were similar to those
      for NH listeners. BKB-SIN scores and ANL scores were not systematically related
      to one another. Each measure accounted for more than one third of the variance in
      CI users' aided APHAB Global scores; together, the two measures accounted for 72%
      of that variance. CONCLUSIONS: Both speech recognition in noise and noise
      tolerance are strongly associated with CI users' self-perceived communication
      ability. The two measures seem to reflect different factors that influence an
      individual's communication experience; thus, both may provide useful clinical
      information. The establishment of formal criteria for BKB-SIN scores and ANL
      scores that are predictive of excessive communication difficulty may help to
      identify CI users who could benefit from additional audiologic rehabilitation.

PMID- 19390442
TI  - The relationship of audiometric thresholds elicited with pulsed, warbled, and
      pulsed-warbled tones in adults with normal hearing.
AB  - OBJECTIVE: American Speech-Language-Hearing Association (ASHA) guidelines allow
      pulsed and warbled tones in measuring audiometric thresholds and include test
      frequencies of 3000 and 6000 Hz. However, no research has examined the
      relationship between thresholds obtained with these stimuli at these frequencies.
      This study investigated the relationship between thresholds obtained with pulsed,
      warbled, and pulsed-warbled tones. DESIGN: Thresholds from 25 listeners were
      obtained using pulsed, warbled, and pulsed-warbled tones at test frequencies
      recommended by ASHA. RESULTS: Thresholds elicited with pulsed, warbled, and
      pulsed-warbled tones did not significantly differ. CONCLUSIONS: Findings support
      using pulsed, warbled, and pulsed-warbled tones for threshold measurements at the
      frequencies recommended by ASHA.

PMID- 19390443
TI  - Quality and safety guidelines of postanaesthesia care: Working Party on Post
      Anaesthesia Care (approved by the European Board and Section of Anaesthesiology,
      Union Europeenne des Medecins Specialistes).
AB  - Postanaesthesia care units are standard parts of hospital care in most European
      Union countries. Their main purpose is to identify and immediately treat early
      complications of surgery or anaesthesia, before they develop into deleterious
      problems. This review, prepared by the Working Party on Post Anaesthesia Care of
      the European Board of Anaesthesiology. European Union of Medical Specialists
      (Union Europeenne des Medecins Specialistes) and approved by the European Board
      and Section of Anaesthesiology, gives recommendations on relevant aspects of
      organization, responsibilities, methods, safety and quality control of
      postanaesthesia care.

PMID- 19390444
TI  - Less invasive indicators of changes in thermodilution cardiac output by
      ventilatory changes after cardiac surgery.
AB  - BACKGROUND AND OBJECTIVE: We studied whether changes in less invasive,
      noncalibrated pulse-contour cardiac output (by modified ModelFlow, COmf) and
      derived stroke volume variations (SVV), as well as systolic and pulse pressure
      variations, predict changes in bolus thermodilution cardiac output (COtd), evoked
      by continuous and cyclic increases in intrathoracic pressure by increases in
      positive end-expiratory pressure (PEEP) and tidal volume (Vt), respectively.
      METHODS: Prospective study on 17 critically ill postcardiac surgery patients on
      full mechanical ventilatory support, in the intensive care unit. RESULTS: In
      contrast to systolic pressure variation and pulse pressure variation, SVV
      increased from (mean +/- SD) 6.2 +/- 4.4 to 8.1 +/- 5.6 at PEEP 10 cmH2O (P =
      0.064) and to 7.8 +/- 3.5% at PEEP 15 cmH2O (P = 0.031), concomitantly with a 12
      +/- 7 and 11 +/- 8% decrease in COmf and COtd (P < 0.001), respectively. For
      pooled data, changes in COmf correlated with those in COtd (r = 0.55, P = 0.002),
      but changes in SVV did not. Variables did not change when Vt was increased up to
      50%. CONCLUSION: A fall in COmf is more sensitive than a rise in SVV, which is
      more sensitive than systolic pressure variation and pulse pressure variation, in
      tracking a fall in COtd during continuous (and not cyclic) increases in
      intrathoracic pressure, in mechanically ventilated patients after cardiac
      surgery. This suggests a reduction in biventricular preload as the main factor in
      decreasing cardiac output and increasing SVV with PEEP.

PMID- 19390445
TI  - Relation between personality and quality of postoperative recovery in day surgery
      patients.
AB  - BACKGROUND AND OBJECTIVE: Personality factors have been found to influence long
      term postoperative depressive symptoms, health and distress in inpatients. To our
      knowledge, no studies have analysed whether the personality traits of day surgery
      patients relate to postoperative recovery. Hence, this study aims to explore
      possible relationships between personality traits and the quality of
      postoperative recovery in patients undergoing day surgery. METHODS: Our study
      used a consecutive sample of 260 day surgery patients to explore possible
      relationships between personal traits, measured by a short Big Five scale, and
      postoperative recovery, measured by modified Quality of Recovery-40, on
      postoperative days 1, 7 and 14. RESULTS: We found a positive correlation in
      changes of 'physical independence' and 'extroversion' (r = 0.20; P = 0.010) and
      'intellect' (r = 0.18; P = 0.021) on postoperative days 1 and 7. These
      correlations were not observed on postoperative day 14. With regard to the change
      between days 7 and 14, correlations were found between 'physical interdependence'
      and 'agreeableness' and between 'physical interdependence' and
      'conscientiousness' (r = -0.17; P = 0.028-0.030 for both). CONCLUSION: Day
      surgery patients appear to be a homogenous group with stable personalities,
      demonstrating some minor correlations between personality traits and the quality
      of postoperative recovery on days 1, 7 and 14. However, further studies are
      needed.

PMID- 19390446
TI  - Left ventricular end-diastolic area is a measure of cardiac preload in patients
      with early septic shock.
AB  - BACKGROUND AND OBJECTIVE: Central venous pressure, intrathoracic blood volume,
      and left ventricular end-diastolic area are reliable measures of cardiac preload
      under stable clinical conditions. The purpose of this study was to compare
      different preload parameters over 24 h under conditions of multiple, frequently
      changing treatments in early septic shock. METHODS: In 28 mechanically ventilated
      patients within 6 h of the onset of septic shock, left ventricular end-diastolic
      area was measured using transoesophageal echocardiography. Intrathoracic blood
      volume, stroke volume variation, and central venous pressure were analysed as
      preload parameters. The relation between parameter changes and changes in therapy
      was examined with respect to cardiac index and stroke volume index. RESULTS:
      Regarding preload variables, linear regression analyses revealed a significant
      correlation between left ventricular end-diastolic area and stroke volume index
      (r=0.59, P<0.001) and cardiac index (r=0.41, P<0.001), respectively. Changes in
      left ventricular end-diastolic index and intrathoracic blood volume index
      reflected changes in the stroke volume index, whereas central venous pressure did
      not. Myocardial responsiveness also failed to predict changes in the stroke
      volume index. CONCLUSION: Only the left ventricular end-diastolic area index may
      help predict preload in ventilated patients with early septic shock.

PMID- 19390447
TI  - Acute memory phase of sevoflurane preconditioning is associated with sustained
      translocation of protein kinase C-alpha and epsilon, but not delta, in isolated
      guinea pig hearts.
AB  - BACKGROUND AND OBJECTIVE: Anaesthetic preconditioning (APC) exerts
      cardioprotective effects by reducing infarct size and improving recovery of
      contractile function after ischaemia-reperfusion. The interval between brief
      exposure to volatile anaesthetic and sustained ischaemia, the acute memory phase,
      is dependent on intracellular signalling mediating this cardioprotection.
      Intramyocyte translocation of protein kinase C (PKC) is known to be a key
      mediator in APC. We examined the relationship between the time frame of the acute
      memory phase of sevoflurane preconditioning and intramyocyte translocation of PKC
      alpha, delta and epsilon to the particulate fraction. METHODS: Isolated perfused
      guinea pig hearts were subjected to 30 min ischaemia and 120 min reperfusion. APC
      was elicited with one minimum alveolar concentration sevoflurane for 10 min.
      Washout times of 10, 30, 60 and 90 min were studied. Contractile recovery was
      assessed by monitoring left ventricular developed pressures. Infarct size was
      determined by triphenyltetrazolium chloride staining. Translocation of PKC was
      examined by western blot analysis. RESULTS: After ischaemia-reperfusion, left
      ventricular developed pressure recovered to a greater degree with APC compared
      with control for washout times of 10 and 30 min, but not 60 and 90 min.
      Similarly, infarct size was reduced for washout times of 10 and 30 min, but not
      60 and 90 min. Sustained translocation of PKC-alpha and epsilon, but not delta,
      was associated with the time frame of the acute memory phase. CONCLUSION: The
      acute memory phase of sevoflurane preconditioning is limited to less than 60 min.
      Sustained translocation of PKC-alpha and epsilon, but not delta, correlates with
      this acute memory phase of sevoflurane preconditioning.

PMID- 19390448
TI  - Comparison of three modes of positive pressure mask ventilation during induction
      of anaesthesia: a prospective, randomized, crossover study.
AB  - BACKGROUND: Mask ventilation of apnoeic patients may be associated with alveolar
      hypoventilation, hyperventilation and gastric insufflation, which may be affected
      by the mode of ventilation during induction of anaesthesia. This study is to
      compare the effect of three modes of positive pressure mask ventilation during
      induction of anaesthesia regarding ventilatory variables and gastric
      insufflation. METHODS: Ninety (90) patients, ASA I-II were included in this
      prospective, randomized, crossover study. Patients were divided into three groups
      of different sequence of modes of ventilation. Each patient was ventilated with
      pressure-controlled ventilation (PCV), manual-controlled ventilation (MCV), and
      volume-controlled ventilation (VCV) during the induction of anaesthesia.
      Respiratory and haemodynamic variables were monitored. Gastric insufflation was
      detected with a stethoscope applied to epigastric area. RESULTS: Haemodynamic
      variables showed no significant differences between the three modes of
      ventilation. PCV was associated with lower peak airway pressures (11.4 +/- 1.2
      cmH2O) compared with MCV and VCV (14.3 +/- 1.7 and 13.3 +/- 1.5 cmH2O;
      respectively P < 0.0001). Inspiratory and expiratory tidal volumes showed no
      significant differences between the three modes. Gastric insufflation was
      detected in one patient (1.1%) in the PCV group compared to three patients (3.3%)
      in the MCV group and three patients (3.3%) in the VCV group. CONCLUSION: We
      concluded that in this model of apnoeic patients with an unprotected airway, PCV
      was associated with lower peak airway pressure which may provide additional
      patient safety.

PMID- 19390449
TI  - Facilitating intubation during left molar approach for laryngoscopy.

PMID- 19390450
TI  - Association between frequency and intensity of recreational physical activity and
      epithelial ovarian cancer risk by age period.
AB  - The objective of this study was to examine the association between recreational
      physical activity across the life span and epithelial ovarian cancer. This
      relationship was investigated using data from the Ontario arm of the National
      Enhanced Cancer Surveillance Study, a Canadian population-based case-control
      study. Data were collected from 240 epithelial ovarian cases and 891 female
      controls using a self-administered questionnaire. The frequency and intensity of
      recreational activity in four age periods (mid-teens, early 30s, early 50s, 2
      years ago) were examined. Odds ratios (OR) and 95% confidence intervals (CI) were
      estimated using multivariate logistic regression. Participation up to two
      times/week, but not more than two times/week, in strenuous recreational activity
      in mid-teens (OR = 1.69, 95% CI=1.15-2.49) and early 30s (OR = 1.45, 95% CI=1.03
      2.05) was associated with increased risk of ovarian cancer. For activity 2 years
      ago, participation in both strenuous activity (OR = 0.69, 95% CI=0.47-1.01) and
      moderate activity (OR = 0.55, 95% CI=0.34-0.88) up to two times/week was
      associated with reduced ovarian cancer risk. Participating more than two
      times/week was not associated with ovarian cancer risk. Strenuous activity
      performed in early 50s and moderate activity performed in mid-teens, early 30s,
      and early 50s were unrelated to risk. In conclusion, strenuous recreational
      activity early in life may increase the risk of ovarian cancer, whereas more
      recent recreational activity may reduce the risk.

PMID- 19390451
TI  - Non-popliteal synovial rupture.
AB  - The ruptured popliteal synovial cyst is a common complication of chronic knee
      arthritis. In contrast, non-popliteal synovial rupture is less well recognized
      and may present a diagnostic dilemma. We report an 81-year-old woman who
      presented with chest wall pain and ecchymosis. Ultrasonography of the shoulder
      region readily diagnosed a dissecting parasynovial cyst. She developed the
      unusual complication of contralateral recurrence. Literature review revealed a
      small but important set of non-popliteal synovial ruptures in the regions of the
      shoulder, elbow, wrist, spine, hip, knee, and ankle. Local swelling,
      inflammation, ecchymosis, and nerve impingement may mimic other conditions.
      Awareness of the clinical presentations and a high index of suspicion are
      required to avoid diagnostic confusion. Management data are limited to case
      reports of arthrocentesis, injection, and very rarely, surgery.

PMID- 19390452
TI  - Sialolipoma of the parotid gland.
AB  - A 33-year-old male patient with a slow-growing, painless, well-circumscribed soft
      tissue mass on the left parotid region is presented. The clinical impression was
      that of a benign salivary gland tumor. The tumor was situated in the superficial
      lobe of the gland, and a superficial parotidectomy was performed, with
      preservation of the facial nerve. Histopathologic examination results revealed a
      sialolipoma of the parotid gland and a lesion that consisted of both mature
      adipose tissue and glandular elements. Sialolipomas share similar clinical
      features with conventional lipomas of the salivary glands. Preoperative diagnosis
      is generally difficult, and computed tomographic scanning is useful in defining
      these benign parotid gland masses. Superficial parotidectomy is the usual
      surgical treatment for parotid gland superficial lobe lipomas, with near-total
      absence of recurrence.

PMID- 19390453
TI  - Pfeiffer syndrome twins: despite improved correction in one twin, growth
      disturbance results in similar need for subsequent monobloc advancement.
AB  - BACKGROUND: Twins with Pfeiffer syndrome (or acrocephalosyndactyly) had a similar
      phenotypic appearance with findings of classic or type 1 Pfeiffer syndrome,
      including bicoronal and sagittal craniosynostoses, midface hypoplasia, and broad
      thumbs/toes. We document their treatment with 2 monobloc advancements and discuss
      growth disturbances in craniofacial dysostosis. METHODS: At 6 months, both twins
      underwent release of multisuture (bilateral coronal and sagittal) fusions for
      improvement of scaphocephalic shape and multisuture release; however, one twin
      had a more aggressive procedure with advancement of the frontal-orbital region.
      Despite improved initial correction by one twin, at 5 years of age, both twins
      presented with midface hypoplasia and exorbitism and underwent a monobloc
      distraction procedure with similar 20-mm advancements. Comparative analysis by
      our craniofacial multidisciplinary team included perioperative reports, computed
      tomographic scans, cephalograms, parent questionnaires, and physician surveys.
      RESULTS: Both twins had an improved confidence interval scores from 84 to 68 and
      82 to 69 postoperatively. In 6-month follow-up, the Whitaker score of the first
      twin was 2.8, whereas that for the second twin with the frontal-orbital
      advancement was 1.2. Preschool expressive and receptive tests yielded 97 and 95,
      and 97 and 98, and developmental testing was similar between the twins. Global
      evaluations were equivalent to age-matched controls, and memory and attention
      skills were within normal limits. Parental surveys showed a high level of
      satisfaction after all procedures in both twins. CONCLUSIONS: Our study
      demonstrates that the phenotypic outcome for both twins remained unchanged when
      comparing a more aggressive surgery to less aggressive surgery as an infant. The
      genetic mutation may have overridden the different surgical interventions. Both
      twins ultimately required 2 subsequent monobloc corrections.

PMID- 19390454
TI  - Mucosa Z-plasty for correction of transverse facial cleft.
AB  - PURPOSE: The aim of this study was to explore a new method for transverse facial
      cleft correction to improve dynamic outcome. METHODS: In accordance with the
      traditional technique, we used another Z-plasty to reconstruct a commissure to
      obtain cosmetic outcome. RESULT: The contour of the baby's face was repaired,
      which is better than that achieved by the traditional technique. CONCLUSIONS: Z
      plasty is an ideal technique for transverse facial cleft correction.

PMID- 19390455
TI  - Segmental osteotomy in the treatment of obsolete orbitozygomatic fractures.
AB  - Different kinds of orbitozygomatic fractures lead to different levels of orbital
      structural destructions. Although the magnitude of the management of
      orbitozygomatic fractures varies considerably, an unsolved and important question
      remains regarding how to select the best surgical modality according to different
      kinds of fractures. Among 26 cases of unilateral noncomminuted orbitozygomatic
      fractures, a segmental osteotomy technique was used to repair the displaced
      orbitozygomatic complex. The fragment contributing to the orbital structure was
      mobilized and reduced, whereas the fragment without contribution to the orbital
      structure was not mobilized and left in situ. Next, the cuneate fragment was
      imbricated with the orbital osteotomy sites unilaterally or bilaterally.
      Miniplates and screws were used to span the osteotomy sites and provided fixation
      once the alignment of the orbit was achieved. The mean difference in volume
      between fractured orbits preoperatively and postoperatively was 2.47 mL. The mean
      difference in ocular globe projection was 2.76 mm. When postoperative results
      were compared with those of the preoperative site, statistically significant
      difference was noted. At follow-up 1 year postoperatively, the management of
      orbitozygomatic fractures using segmental osteotomy reduces complications and
      attains aesthetically satisfying results. Subjective assessment of the patients'
      globe position found that 88.5% of the patients were satisfied with the outcome,
      and 11.5% of the patients found it unacceptable. Compared with the traditional
      method, segmental osteotomy is a simple technique requiring less dissection and
      can reconstruct the orbital anatomic structure and restore globe position
      effectively.

PMID- 19390456
TI  - Sociodemographic and etiologic differences of malignant orofacial tumors in Iran.
AB  - Oral malignant tumors are the sixth most common malignancy in the world, and
      there is a recent trend of rising incidence of these tumors in young patients.
      The aim of this study was to compare demographic and etiologic data from young
      and old patients with orofacial malignant tumors. Data were obtained by
      retrospective analysis of files of patients with malignant orofacial tumors, who
      were categorized into 2 groups: the young group (< or = 40 years old) an the
      older group (> 60 years old). Both younger and older groups showed male
      predilection (male-female ratio was 1.05:1 and 2.4:1 in the younger and older
      groups, respectively). Consumption of tobacco and alcohol was reported by 13
      young patients (31.7%) and by 45 older patients (62.5%). Tongue was the most
      common site for older group (37.5%), whereas that for the younger group was the
      parotid (29.3%). We found that the pattern of malignant orofacial tumors in the
      young age group was changed, and these tumors can occur in young patients who
      report no tobacco or alcohol use.

PMID- 19390457
TI  - Radiologic evaluation of the ear anatomy in pediatric cholesteatoma.
AB  - The aim of the study was to describe computed tomography (CT) findings in middle
      ear cholesteatoma in pediatric patients. A cohort of 32 children with
      cholesteatoma (3-14 years old) entered the study. From them, 30 presented
      acquired cholesteatoma (AC), and 2 presented congenital cholesteatoma. All of the
      children were investigated using CT before surgery of the middle ear and mastoid.
      Computed tomography was performed with 1- or 2-mm axial and coronal sections of
      both temporal bones. Nineteen children with AC (63.3%) revealed a diffuse soft
      tissue density isodense with muscle, whereas in 6 of them, the mass mimicked
      inflammation. The remaining revealed localized soft-tissue mass with partially
      lobulated contour. In AC, ossicular erosion was detected in 23 cases (76.7%),
      abnormal pneumatization in 19 cases (63.3%), and erosion-blunting of spur and
      enlargement of middle ear or mastoid in 8 cases (26.7%). The 2 congenital
      cholesteatomas revealed soft-tissue mass with polypoid densities, while a
      semicircular canal fistula was detected in one of them. High-resolution CT
      facilitates early diagnosis and appropriate treatment of pediatric cholesteatoma
      by assessing the anatomic abnormalities and the extent of disease, which are
      crucial in middle ear and mastoid surgery.

PMID- 19390458
TI  - Accelerated development of the first and second mandibular molars after
      distraction osteogenesis of the mandible in patients with hemifacial microsomia.
AB  - Although distraction osteogenesis of the mandible in patients with hemifacial
      microsomia (HFM) before the mixed dentition period is widely performed, long-term
      follow-up information on dental problems is limited. We evaluated the long-term
      effect of distraction osteogenesis on dental development by comparing Nolla's
      developmental stages of the first and second molars between the affected and
      unaffected sides of the mandible. Forty-five patients with unilateral HFM who
      received distraction osteogenesis of the mandible between the ages of 5 and 8
      years and whose dental status was followed for more than 2 years were selected
      for this study. The patients were divided into 2 groups: group I (n = 28)
      consisted of patients with Pruzansky types I and IIA and group II (n = 17)
      consisted of patients with types IIB and III. Panoramic radiographs at T0 (1
      month before distraction), T1 (6 months to 1 year after distraction), T2 (2-3
      years after distraction) were reviewed. Nolla's stages for the first and second
      molars were compared at each of the abovementioned times between the affected and
      unaffected sides using Wilcoxon signed-rank test. In group I, there was no
      differences observed in Nolla's stages of the first and second molars in
      comparisons between the affected and unaffected sides of the mandible. However,
      in group II, at T0, there was a significant difference in Nolla's stage of the
      first and second molars in comparisons between the affected and unaffected sides.
      Over time, tooth development was accelerated, and eventually, there was no
      difference in Nolla's stage between the affected and unaffected sides at T1 and
      T2. Patients with severe HFM can benefit from distraction osteogenesis of the
      mandible. The results of this study showed that this procedure could normalize
      the delayed development and eruption of the first and second molars.

PMID- 19390460
TI  - A method for imputing the impact of health problems on at-work performance and
      productivity from available health data.
AB  - OBJECTIVE: To develop a method for imputing the work performance and productivity
      impact of illness and treatment from available data. METHODS: Using data from
      four studies of musculoskeletal disorders (eg, osteoarthritis) and pain, we
      modeled the relationships between scores from the Work Limitations Questionnaire
      (WLQ), a validated measure of health-related limitations in work performance and
      productivity, and a series of validated health measures (eg, a pain scale).
      RESULTS: The 15 health and 5 WLQ variables were significantly associated in 115
      of 116 study-specific models (P < 0.05). CONCLUSION: Fifteen commonly collected
      health variables may be used to predict WLQ impact (increase or decrease) for
      samples with musculoskeletal pain and physical impairments to help fill
      information gaps.

PMID- 19390459
TI  - Circulating angiopoietin-2 in essential hypertension: relation to
      atherosclerosis, vascular inflammation, and treatment with
      olmesartan/pravastatin.
AB  - BACKGROUND: Endothelial activation has emerged as an early event in the
      pathogenesis of cardiovascular disease. Angiopoietin-2 (Ang-2) has been
      identified as a nonredundant endothelial-specific facilitator of vascular
      responsiveness to inflammatory stimuli. We have earlier shown that angiotensin II
      receptor blocker (ARB) reduces mediators of vascular inflammation in hypertension
      and cardiovascular disease. We aimed at studying the effect of ARB and/or 3
      hydroxy-3-methyl-glutaryl-CoA blockade on Ang-2 and the association between
      vascular inflammation markers and Ang-2 levels in hypertensive patients. METHODS:
      We assessed a panel of vascular inflammation markers and Ang-2 during 12 weeks of
      therapy with the ARB olmesartan (n = 94) or placebo (n = 96) in a prospective,
      double-blind, multicenter study in patients with essential hypertension (re
      evaluation of the European Trial on Olmesartan and Pravastatin in Inflammation
      blood samples). Pravastatin was added to the double-blind therapy at week 6 in
      both arms. The association of demographic variables and inflammation markers with
      Ang-2 has been investigated. RESULTS: Initial Ang-2 concentrations in the study
      population were elevated compared with healthy controls (4.23 +/- 3.1 versus 0.88
      +/- 0.43 ng/ml; P < 0.0001). Ang-2 was higher in the elderly (P = 0.01), women (P
      < 0.001), and in the presence of atherosclerosis (P = 0.02). Ang-2 correlated
      significantly with soluble TEK tyrosine kinase-2, interleukin-6, vascular cell
      adhesion molecule-1, and inter-cellular adhesion molecule-1. Surprisingly,
      neither monotherapy with olmesartan or pravastatin nor the combination therapy
      affected Ang-2 concentrations. CONCLUSION: Ang-2 concentrations are elevated in
      hypertensive patients, particularly those with atherosclerosis, possibly
      reflecting pronounced endothelial activation. ARBs effectively decreased several
      inflammatory mediators, but did not affect vascular responsiveness in an Ang-2
      dependent manner. Elevated Ang-2 levels in hypertensive patients correlate with
      adhesion molecules.

PMID- 19390461
TI  - The Vertical Expandable Prosthetic Titanium Rib in the treatment of spinal
      deformity due to progressive early onset scoliosis.
AB  - The Vertical Expandable Prosthetic Titanium Rib (VEPTR) is a technique developed
      for the treatment of progressive early onset scoliosis. This vertically placed
      device uses distraction to indirectly elongate the spine and chest, stabilizing
      the progression of the spinal deformity while preserving spinal growth. Thoracic
      spine and chest wall deformity are usually correlated; therefore, elongation of
      the chest wall will increase the space available for the lung and improve
      respiratory mechanics in patients with early onset scoliosis. We conducted a
      retrospective study of 17 patients with early onset scoliosis treated with the
      VEPTR technique. The medical records, imaging studies, and follow-up physical
      examinations were evaluated. The patient population consisted of 17 primary VEPTR
      implantations and 33 expansion surgeries with a mean follow-up of 25 months. Our
      results show that there was an improvement in the coronal plane deformity between
      the presurgical and postsurgical Cobb angles, preoperative Cobb angle of 59
      degrees (range 38-77) to postoperative 35 degrees (range 10-70), resulting in an
      average decrease of 59% in the Cobb angle (P<0.001). The thoracic kyphosis was
      maintained at anatomically normal values. The surgical technique preserved the
      space available for the lung. The complication rate was 13%, which includes
      infection, device migration, and rib fracture. The analysis of the data shows
      that the natural history of the progressive spinal deformity was improved in all
      patients. This preliminary report reaffirms that the VEPTR implantation is a safe
      and efficient method for the treatment of early onset scoliosis.

PMID- 19390462
TI  - Memory at midlife: perception and misperception.

PMID- 19390463
TI  - Efficacy and safety of vaginal estriol and progesterone in postmenopausal women
      with atrophic vaginitis.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy and safety of
      intravaginal estriol and progesterone on atrophic vaginitis in postmenopausal
      women. METHODS: Under a physician-sponsored Investigational New Drug application,
      19 healthy postmenopausal women with atrophic vaginitis received vaginal
      suppositories containing estriol (1 mg) and progesterone (30 mg). The
      participants were instructed to insert one suppository intravaginally once daily
      for 2 weeks and thrice weekly for a total of 6 months. Vaginal pH, Vaginal
      Maturation Index, urinalysis, self-reported vaginal dryness, menopausal quality
      of life, and serum estriol and progesterone levels were measured at enrollment
      and after 3 and 6 months of suppository use. Endometrial biopsies were obtained
      at enrollment and at 6 months. After 2 weeks of therapy, six participants had
      serum estriol and progesterone measured. RESULTS: The Vaginal Maturation Index,
      vaginal pH, and vaginal dryness rating improved significantly at 3 and 6 months
      compared with baseline. Menopausal quality of life scores improved significantly
      in all domains, with the sexual subscale showing the most improvement. There were
      no cases of endometrial hyperplasia after 6 months of suppository use. Serum
      preinsertion estriol at week 2 and months 3 and 6 were similar to baseline
      levels. Serum preinsertion progesterone increased but returned to baseline
      preinsertion levels at month 6, and preinsertion levels were significantly less
      at month 6 compared with month 3. CONCLUSIONS: Intravaginal administration of a
      combination estriol and progesterone agent to women with atrophic vaginitis may
      represent a safe and effective alternative to systemic hormone replacement,
      although this study was not adequate to provide proof of efficacy given that it
      was uncontrolled.

PMID- 19390464
TI  - Initial laparoscopic access in postmenopausal women: a preliminary prospective
      study.
AB  - OBJECTIVE: Estrogen loss at menopause has a profound influence on skin, with
      postmenopausal atrophy and loss of tone and elasticity. Because more than 50% of
      major laparoscopic complications occur during initial entry under the abdominal
      skin, the efficacy and the safety of two laparoscopic access techniques were
      compared in postmenopausal women. METHODS: One hundred eighty-six postmenopausal
      women underwent laparoscopic surgery for simple ovarian cysts: 89 were assigned
      to direct optical access (DOA), abdominal entry (group I), and 97 to the classic
      closed Veress needle approach, pneumoperitoneum, and trocar entry (group II). The
      following parameters were compared: time needed for entry into the abdomen,
      occurrence of vascular and/or bowel injury, and blood loss. Results were analyzed
      using SAS software, considering P value less than 0.05 as significant. RESULTS:
      No statistically significant differences were observed in the occurrence of major
      vascular and/or bowel injury between the two techniques (P > 0.05), whereas time
      for abdominal entry was significantly reduced in the DOA group, as well as the
      occurrence of minor vascular injuries (P < 0.05). CONCLUSIONS: Results of this
      preliminary comparison on the DOA and the Veress methods, commonly used by
      gynecologists, suggest that the visual entry system offers a statistical
      advantage over the closed Veress needle approach, in terms of time saving and
      limiting minor vascular injuries, thus enabling a safe and fast visually guided
      entry in postmenopausal women.

PMID- 19390465
TI  - Myocardial perfusion defects in right ventricular apical pacing are caused by
      partial volume effects because of wall motion abnormalities: a new model to study
      gated myocardial SPECT with the pacemaker on and off.
AB  - BACKGROUND: Myocardial perfusion defects have been shown in patients with
      abnormal intraventricular conduction. These defects have been ascribed to
      regional differences in myocardial blood flow caused by the abnormal activation.
      This proof of the concept study assesses the effects of abnormal electrical
      activation and subsequent wall motion abnormalities of the left ventricle on
      myocardial perfusion in a pacing model. METHODS: Fourteen patients with normal
      atrio-ventricular (AV) and intraventricular conduction with a right ventricular
      apical (RVA) pacemaker for brady-tachycardia syndrome were studied to allow for
      intrapatient comparison. Tc-sestamibi was injected in atrial inhibited (AAI)
      pacing mode allowing uptake during normal intraventricular conduction. Imaging
      was performed with AAI pacing and the second image was acquired directly after
      the first scan with AV pacing with a short AV-interval ensuring complete AV
      pacing with abnormal ventricular activation patterns (RVA pacing). Left
      ventricular ejection fraction (LVEF), wall motion score and myocardial perfusion
      score (SSS) were assessed with gated single photon emission computed tomography
      (SPECT) during normal conduction (AAI) and with RVA pacing. RESULTS: Left
      ventricular ejection fraction was normal in all patients. During AAI, three of 14
      patients showed wall motion abnormalities, mean wall motion score 0.9+/-1.8 with
      a mean SSS 0.6+/-1.5 increasing to 4+/-6.2 and 3.6+/-5.8 (P<0.01), respectively
      during RVA pacing. Wall motion abnormalities were found in the apex, inferior,
      inferoseptal and septal walls. CONCLUSION: Despite a fixed amount of tracer
      activity in the myocardium, larger and more perfusion defects were visible during
      RVA pacing compared with normal conduction. The site and severity of the
      perfusion defects correlates with abnormal wall motion because of this pacing
      mode. This implies that abnormal wall motion is at least partly responsible for
      the apparent myocardial perfusion defects.

PMID- 19390466
TI  - Treatment options for myopia.
AB  - Myopia is a significant public health problem and its prevalence may be
      increasing over time. The main treatment options of single vision spectacle
      lenses, contact lenses, and refractive surgery do not slow the accompanying eye
      growth or retard the physiological changes associated with excessive axial
      elongation. High myopia is a predisposing factor for retinal detachment, myopic
      retinopathy, and glaucoma, contributing to loss of vision and blindness. The high
      prevalence of myopia and its prominence as a public health problem emphasize the
      importance of finding effective treatments that slow myopia progression and axial
      elongation. Treatments that have been investigated include various types of
      spectacle lenses and contact lenses, as well as pharmaceutical agents such as
      atropine and pirenzepine. The bulk of evidence from well-conducted studies shows
      that overall, most therapies for myopia have small treatment benefits that last
      for a relatively short period of time or have significant side effects. Some
      therapies may be more effective in subsets of myopic children. This review of
      treatment options for myopia will emphasize recent results from well-designed
      clinical studies and will suggest possible future therapies.

PMID- 19390467
TI  - Clinical applications of power vectors.
AB  - The study of infant vision is closely coupled to the study of the refraction,
      change in refraction over time, and the effect of spectacle correction on visual
      development. Frequently, reports are limited to descriptions of spherical
      equivalent or cylinder power without regard to axis, as data are frequently
      collected in the clinical format of sphere, cylinder, and axis (S, C, A).
      Conversion from clinical notation to a power vector representation of refraction
      allows unambiguous description of how refractions change over time and differ
      between repeated measurements. This article presents a series of examples of
      Microsoft Excel spreadsheet formulas that make the conversion from clinical
      notation to power vector format, and provides examples of useful applications of
      these methods.

PMID- 19390469
TI  - Binocular adaptation to +2 D lenses in myopic and emmetropic children.
AB  - PURPOSE: To compare vergence adaptation to +2 D addition lenses in myopic and
      emmetropic children and to evaluate the influence of the accommodative-vergence
      crosslink (AC/A ratio) on this adaptation. METHODS: Nine myopic and 11 emmetropic
      children fixated a near target at a distance of 33 cm. Measures of binocular and
      monocular accommodation and phoria were obtained during a 20-min near task with
      and without +2 D lenses. Response AC/A ratios were determined from the
      experimental results. Vergence adaptation was quantified by the magnitude of
      reduction in phoria and the percentage of completeness (PC, return of adapted
      phoria to habitual level) after the near task. RESULTS: Myopic children showed
      significantly higher AC/A ratios, which led to greater lens-induced exophoria and
      a greater demand for vergence adaptation. Both refractive groups showed
      significant vergence adaptation; however, myopes exhibited significantly reduced
      (p < 0.01) magnitudes compared with emmetropes (myopes = 3.95 +/- 0.15 Delta;
      emmetropes = 4.41 +/- 0.08 Delta). The mean PC was also significantly (p < 0.001)
      reduced in myopes (61.02 +/- 1.57) compared with emmetropes (76.6 +/- 2.10).
      There was a significant correlation between magnitude of adaptation and AC/A in
      both the refractive groups; however, myopes consistently showed reduced
      magnitudes compared to emmetropes. AC/A ratio influenced PC in emmetropic but not
      myopic children. In the accommodation system, +2 D lenses eliminated the
      accommodative lags observed in myopic children during natural viewing conditions.
      These lenses resulted in a small over-focus (-0.24 +/- 0.27 D) at the onset of
      near work, which decreased during sustained viewing through the near add.
      CONCLUSIONS: Myopic children demonstrate reduced magnitude and completeness of
      vergence adaptation to +2 D lenses. The magnitude of vergence adaptation varied
      with AC/A in both refractive groups; however, the presence of myopia
      differentiated the amount of adaptation for all AC/A ratios. Conversely, the
      degree of completeness appears to be primarily associated with the type of
      refractive error.

PMID- 19390468
TI  - Stereoacuity outcomes after treatment of infantile and accommodative esotropia.
AB  - PURPOSE: To review what is known about the normal maturation of stereoacuity, the
      stereoacuity deficits associated with infantile and accommodative esotropia, the
      rationale for making improved stereoacuity a goal of treatment, and strategies
      for improving stereoacuity outcomes. METHODS: Studies of stereoacuity maturation
      during normal development, studies of stereoacuity outcomes after treatment for
      infantile and accommodative esotropia, and studies of primate models of esotropia
      are reviewed. RESULTS: Stereoacuity maturation normally proceeds rapidly during
      the first year of life. Infantile and accommodative esotropia are associated with
      profound and permanent disruption of stereopsis. Although rehabilitation of
      stereoacuity after treatment of esotropia remains a challenge, even the
      achievement of subnormal stereoacuity may have real benefits to the child.
      CONCLUSIONS: Some abnormalities in stereoacuity may exist before the onset of
      esotropia, but others may result directly from abnormal binocular experience.
      Several strategies for improving stereoacuity outcomes in esotropia are currently
      under active investigation. Improved stereoacuity outcomes are associated with
      better long-term stability of alignment, reduced risk for and severity of
      amblyopia, improved achievement of sensorimotor developmental milestones, better
      reading ability, and improved long-term quality of life.

PMID- 19390470
TI  - Corneal power and astigmatism in Down syndrome.
AB  - PURPOSE: Corneal and crystalline lens shape differ in Down syndrome (DS) compared
      with developmentally normal populations. This study specifically explored the
      association between corneal curvature and refractive error for the first time in
      DS. METHODS: Participants were 29 children with 59 age-matched controls (33 males
      and 35 females; mean age 12.4 +/- 1.8 years) and DS (9 to 16 years; 19 males and
      10 females; mean age 12.8 +/- 1.9 years). Corneal curvature was measured using a
      hand-held keratometer. Refractive error was assessed by distance static
      retinoscopy in the control group and Mohindra retinoscopy in the DS group.
      RESULTS: The DS group demonstrated a high frequency and magnitude of refractive
      errors (mean DS + 2.52 +/- 3.00 D; mean controls -0.46 +/- 1.32 D). The majority
      of controls had little or no significant refractive error. DS cornea were
      significantly steeper (mean DS 45.62 +/- 2.13 D; mean controls 43.10 +/- 1.37 D).
      Neither DS nor control data demonstrate significant relations between corneal and
      total refractive power (M vector). Astigmatic errors in the DS group were more
      frequently oblique and demonstrated strong right-left specificity. The DS data
      did not demonstrate a significant association between corneal and total
      astigmatism along principal meridians (J0), however, a significant relation was
      found for the control data (linear regression, r = 0.51, p < 0.0001). No
      significant association between corneal and total oblique astigmatism (J45) was
      demonstrated by either DS or control data. CONCLUSIONS: The study is the first to
      explicitly investigate the association between corneal power and refractive error
      in children with DS. The majority of the DS group have significant refractive
      errors including an increased prevalence of oblique astigmatism. Corneal
      curvature in DS is not related to spherical (M) or astigmatic (J0, J45)
      refractive error. Further research is required to better understand the
      association between the ocular structures of the DS eye and their impact on
      functional vision.

PMID- 19390472
TI  - Albinism: classification, clinical characteristics, and recent findings.
AB  - PURPOSE: To describe the clinical characteristics and recent findings in the
      heterogeneous group of inherited disorders of melanin biosynthesis grouped as
      "albinism." METHODS: The current classification of albinism, and the cutaneous,
      ocular, and central nervous system characteristics are presented. Recent clinical
      findings are summarized. RESULTS: Albinism is now classified based on genes known
      to be responsible for albinism. Foveal hypoplasia is invariably present and
      individuals with albinism often have delayed visual development, reduced vision,
      nystagmus, a positive angle kappa, strabismus, iris transillumination, and absent
      or reduced melanin pigment in the fundi. A visual-evoked potential can document
      the excessive retinostriate decussation seen in albinism. Grating acuity can be
      used to document delayed visual development in preverbal children. Glasses are
      often needed to improve visual acuity and binocular alignment. CONCLUSIONS:
      Albinism is caused by several different genes. Heterogeneity in clinical
      phenotype indicates that expressivity is variable.

PMID- 19390471
TI  - VEP vernier, VEP grating, and behavioral grating acuity in patients with cortical
      visual impairment.
AB  - PURPOSE: Cortical visual impairment (CVI) is a leading cause of bilateral vision
      impairment. Because many patients with CVI cannot perform an optotype test, their
      acuity is often measured with a grating stimulus using a preferential looking
      (PL) test or the visual-evoked potential (VEP) recording. The purpose of this
      study is to determine the relationship among VEP vernier acuity, VEP grating
      acuity, and behavioral grating acuity in patients with CVI. METHODS: Sweep VEP
      vernier acuity, sweep VEP grating acuity, and behavioral grating acuity (measured
      with PL cards) were measured in 29 patients with CVI. The patients ranged in age
      from 3.2 to 22.7 years (mean: 12.3; SD: 5.3). Because the measures of vernier
      acuity and grating acuity have different units, the results were expressed as the
      log deficit (with normal being 30 cycles per degrees and 0.5 arc min,
      respectively). RESULTS: VEP grating acuity loss and VEP vernier acuity loss were
      significantly related (r = 0.70) with a slope of 1.31, indicating that indicating
      that on average, vernier acuity showed a 0.2 log unit deficit compared with VEP
      grating acuity. Behavioral grating acuity loss and VEP grating acuity loss were
      also significantly related (r = 0.64) with a slope of 1.55, indicating that
      behavioral acuity was more reduced (by approximately 0.3 log unit). VEP vernier
      acuity loss and behavioral grating acuity loss were significantly related (r =
      0.66) with a slope of 0.85, indicating that behavioral acuity and VEP vernier
      acuity showed a similar magnitude of reduction. A Bland-Altman comparison between
      the VEP vernier acuity method and the behavioral acuity method showed a flat
      slope (0.30), indicating that the two measures produce similar visual acuity
      measures across the range of acuity levels. CONCLUSIONS: In patients with CVI,
      VEP vernier acuity showed greater deficits than VEP grating acuity and was more
      similar to the behavioral measures of grating acuity.

PMID- 19390473
TI  - Photorefraction of eyes: history and future prospects.
AB  - A brief history of photorefraction, i.e., the refraction of eyes by photography
      or computer image capture, is given. The method of photorefraction originated
      from an optical scheme for secret communication across the Berlin wall. This
      scheme used a lens whose focus about infinity was modulated by a movable
      reflecting surface. From this device, it was recognized that the vertebrate eye
      was such a reflector and that its double-pass pointspread could be used to
      compute its degree of defocus. Subsequently, a second, totally independent
      invention, more accurately termed "photoretinoscopy," used an eccentric light
      source and obtained retinoscopic-like images of the reflex in the pupil of the
      subject's eyes. Photoretinoscopy has become the preferred method of
      photorefraction and has been instantiated in a wide variety of devices used in
      vision screening and research. This has been greatly helped by the parallel
      development of computer and digital camera technology. It seems likely that
      photorefractive methods will continue to be refined and may eventually become
      ubiquitous in clinical practice.

PMID- 19390474
TI  - The teller acuity cards are effective in detecting amblyopia.
AB  - PURPOSE: Detection of amblyopia in infants and toddlers is difficult because the
      current clinical standard for this age group, fixation preference, is inaccurate.
      Although grating acuity represents an alternative, studies of preschoolers and
      schoolchildren report that it is not equivalent to the gold standard optotype
      acuity. Here, we examine whether the Teller Acuity Cards (TAC) can detect
      amblyopia effectively by testing children old enough (7.8 +/- 3.6 years) to
      complete optotype acuity testing. METHODS: Grating acuity was assessed
      monocularly in 45 patients with unilateral amblyopia, 44 patients at risk for
      amblyopia, and 37 children with no known vision disorders. Each child's grating
      acuity was classified as normal/abnormal based on age-appropriate norms. These
      classifications were compared with formal amblyopia diagnoses. RESULTS: Grating
      acuity was finer than optotype acuity among amblyopic eyes (medians: 0.28 vs.
      0.40 logMAR, respectively, p < 0.0001) but not among fellow eyes (medians: 0.03
      vs. 0.10 logMAR, respectively, p = 0.36). The optotype acuity-grating acuity
      discrepancy among amblyopic eyes was larger for cases of severe amblyopia than
      for moderate amblyopia (means: 0.64 vs. 0.18 logMAR, respectively, p = 0.0001).
      Nevertheless, most cases of amblyopia were detected successfully by the TAC,
      yielding a sensitivity of 80%. Furthermore, grating acuity was relatively
      sensitive to all amblyopia subtypes (69 to 89%) and levels of severity (79 to
      83%). CONCLUSIONS: Although grating acuity is finer than optotype acuity in
      amblyopic eyes, most children with amblyopia were identified correctly suggesting
      that grating acuity is an effective clinical alternative for detecting amblyopia.

PMID- 19390475
TI  - Perceptual organization in infancy: bottom-up and top-down influences.
AB  - A program of research on the origins and development of perceptual organization
      during infancy is reviewed. The data suggest that infant perception of visual
      pattern information is guided by adherence to a number of bottom-up, stimulus
      based organizational principles (including common motion, common region,
      connectedness, continuity, proximity, and similarity) that become functional over
      different time courses of development. In addition, not all principles may be
      readily deployed in the manner proposed by Gestalt psychologists and the
      emergence of some may be facilitated by perceptual learning. Moreover, there is
      evidence that the principles can be modulated by top-down influences inclusive of
      object concept knowledge. This body of research indicates that it is necessary to
      analyze stimulus-based automatic organizational processes as well as perceptual
      learning and other top-down processes to understand visual organization and its
      development in infancy.

PMID- 19390476
TI  - Deafness genes in Israel: implications for diagnostics in the clinic.
AB  - The identification of the molecular basis of deafness in the last decade has made
      a remarkable impact on genetic counseling and diagnostics for the hearing
      impaired population. Since the discovery of the most prevalent form of deafness
      associated with mutations in the GJB2 (connexin 26) gene, many other genes have
      been found worldwide, with a subset of these, including unique mutations, in
      Israel. Here, we review the current status of deafness genes in Israel and report
      one known mutation in a syndromic form of deafness, Usher syndrome, described in
      the Jewish Israeli population for the first time. In the future, the
      identification of specific mutations may be relevant for specific types of
      treatment.

PMID- 19390477
TI  - Surfactant protein-A limits Ureaplasma-mediated lung inflammation in a murine
      pneumonia model.
AB  - Ureaplasma respiratory tract colonization stimulates prolonged, dysregulated
      inflammation in the lungs of preterm infants, contributing to bronchopulmonary
      dysplasia (BPD) pathogenesis. Surfactant protein-A (SP-A), a lung collectin
      critical for bacterial clearance and regulating inflammation, is deficient in the
      preterm lung. To analyze the role of SP-A in modulating Ureaplasma-mediated lung
      inflammation, SP-A deficient (SP-A-/-) and WT mice were inoculated
      intratracheally with a mouse-adapted U. parvum isolate and indices of
      inflammation were sequentially assessed up to 28 d postinoculation. Compared with
      infected WT and noninfected controls, Ureaplasma-infected SP-A-/- mice exhibited
      an exaggerated inflammatory response evidenced by rapid influx of neutrophils and
      macrophages into the lung, and higher bronchoalveolar lavage TNF-alpha, mouse
      analogue of human growth-related protein alpha (KC), and monocyte chemotactic
      factor (MCP-1) concentrations. However, nitrite generation in response to
      Ureaplasma infection was blunted at 24 h and Ureaplasma clearance was delayed in
      SP-A-/- mice compared with WT mice. Coadministration of human SP-A with the
      Ureaplasma inoculum to SP-A-/- mice reduced the inflammatory response, but did
      not improve the bacterial clearance rate. SP-A deficiency may contribute to the
      prolonged inflammatory response in the Ureaplasma-infected preterm lung, but
      other factors may contribute to the impaired Ureaplasma clearance.

PMID- 19390478
TI  - Live and heat-killed Lactobacillus rhamnosus GG: effects on proinflammatory and
      anti-inflammatory cytokines/chemokines in gastrostomy-fed infant rats.
AB  - Lactobacillus rhamnosus GG (LGG), a probiotics, ameliorates intestinal and other
      organ inflammation in infant rats. The hypothesis is that live and heat-killed
      LGG have similar effects on decreasing the inflammatory response induced by E.
      coli lipopolysaccharide (LPS) in the infant rat. Using a gastrostomy-fed rat
      model, 7-d-old rat pups were gastrostomy fed with or without live LGG (10(8) or
      10(12) cfu x L(-1) x kg(-1) x d(-1)) for 6 d. In a separate experiment, LPS was
      administered to rat pups with or without live or heat-killed LGG (10(8) cfu x L(
      1) x kg(-1) x d(-1)). Cytokine/chemokine proteins were determined by ELISA or
      multiplex assay. Both live and heat-killed LGG decreased LPS-induced cytokine
      induced neutrophil chemoattractant-1 (CINC-1) production in liver and plasma (p <
      0.05) and also showed a trend (p = 0.09) in lungs. Live and heat-killed LGG
      ameliorated LPS-suppressed IL-10 level in lungs (p < 0.05). Both forms of LGG
      decreased IL-1b production in liver. There was no difference between low and high
      doses of live LGG in the production of CINC-1, TNF-alpha, and myeloperoxidase
      (MPO). There was a trend of increase of claudin-1 in both live and heat-killed
      groups (p = 0.08). In conclusion, both live and heat-killed LGG provided by the
      enteral route decrease LPS-induced proinflammatory mediators and increase anti
      inflammatory mediators.

PMID- 19390479
TI  - Antibiotic prophylaxis improves Ureaplasma-associated lung disease in suckling
      mice.
AB  - Ureaplasma infection is associated with increased lung disease in high-risk
      neonates. Our goal was to determine the impact of antibiotic prophylaxis on
      Ureaplasma and oxygen-induced lung disease in newborn mice. In animal model
      development and prophylaxis experiments, pups were randomly assigned to either
      0.8 or 0.21 inspired oxygen concentration [fraction of inspired oxygen (FiO2)]
      from 1 to 14 d of age and either Ureaplasma or 10 B media daily from 1 to 3 d.
      All pups were observed for growth and survival. Surviving pups had culture and
      PCR evaluated for blood, bronchoalveolar lavage, and lung, and lung weights,
      pathology, morphometry, histology, and immunohistochemistry were determined. In
      prophylaxis experiments, erythromycin, azithromycin, or normal saline was given
      for the first 3 d, and minimum inhibitory concentration and pharmacokinetics were
      determined. In model development, 0.8 FiO2 and Ureaplasma infection survival and
      growth were significantly decreased and lung edema and inflammation were
      significantly increased. In prophylaxis experiments, we observed significantly
      improved survival and growth with azithromycin versus normal saline controls,
      whereas erythromycin was not significantly different from controls, and decreased
      inflammatory response with azithromycin versus normal saline and erythromycin. In
      a neonatal mouse model of Ureaplasma and oxygen-induced lung disease, appropriate
      antibiotic prophylaxis improves survival and morbidity and decreases lung
      inflammation.

PMID- 19390480
TI  - The effects of omega-3 fatty acid supplementation in pregnancy on maternal
      eicosanoid, cytokine, and chemokine secretion.
AB  - The incidence of allergic diseases has increased, and a relation between allergy
      and dietary fatty acids has been proposed. Modulation of the maternal immune
      function during pregnancy may have an impact on future clinical outcomes in the
      child. The aim of this study was to determine the effects of omega (omega)-3 long
      chain polyunsaturated fatty acids (LCPUFA) supplementation during pregnancy on
      the plasma fatty acid composition in relation to the maternal immune function.
      Pregnant women with allergic disease in their immediate family were supplemented
      daily with 2.7 g omega-3 LCPUFA (n = 70) or 2.8 g soybean oil as placebo (n = 75)
      from the 25th gestational week. The proportions of eicosapentaenoic acid and
      docosahexaenoic acid in plasma/serum phospholipids increased in the omega-3
      supplemented group, whereas arachidonic acid decreased during intervention.
      Lipopolysaccharide-induced prostaglandin E2 secretion from whole blood culture
      supernatants (n = 59) decreased in a majority of the omega-3-supplemented mothers
      (18 of 28, p = 0.002). The decreased prostaglandin E2 production was more
      pronounced among nonatopic than atopic mothers. The lipopolysaccharide-induced
      cytokine and chemokine secretion was not affected. Our results indicate that
      omega-3 LCPUFA supplementation during the last trimester may dampen certain
      immune responses involved in allergic inflammation.

PMID- 19390481
TI  - Does intervention in utero preserve the obstructed kidneys of fetal lambs? A
      histological, cytological, and molecular study.
AB  - Ureteropelvic junction obstruction is a common cause of end-stage nephropathy in
      children. Our aim was to investigate whether relief of obstruction in utero can
      alleviate the development of nephropathy. A silastic tube was tied around the
      left superior segment ureter to induce unilateral partial ureteral obstruction in
      22 fetal sheep at 75- 85 d of gestation. Three weeks later, the tubes were
      removed to relieve the obstruction in 10 of the 22 lambs. A sham operation was
      performed on four fetuses (the control). At birth, the lambs were killed, and
      their kidneys were removed to study the changes in histology, podocytes, and
      expression of paired-box 2 (PAX2) and VEGF. In the obstructed kidneys, we
      observed cysts of various sizes in the cortex, fibrosis in the interstitial
      tissue, much decreased number of glomeruli, severe podocyte foot process fusion,
      and markedly increased PAX2 and decreased VEGF expressions. However, relief of
      obstruction preserved the number of glomeruli, significantly increased VEGF
      expression, reduced fusion of the podocyte foot processes, andrestored expression
      of PAX2 to some extent. Thus, relief ofobstruction in utero may prevent or
      attenuate the development ofnephropathy in lambs.

PMID- 19390482
TI  - The effects of disodium cromoglycate on enhanced adherence of Haemophilus
      influenzae to A549 cells infected with respiratory syncytial virus.
AB  - Nontypeable Haemophilus influenzae (NTHi) secondary infection often complicates
      respiratory syncytial virus (RSV) infections. Previous studies have revealed that
      RSV infections enhance NTHi adherence to airway epithelial cells. In this study,
      we investigated the effects of disodium cromoglycate (DSCG) and corticosteroids,
      which are frequently used for the treatment of wheezing often related to RSV
      infections, on the adherence of NTHi to RSV-infected A549 cells. DSCG inhibited
      enhanced adherence of NTHi to RSV-infected A549 cells, whereas dexamethasone
      (Dex) and fluticasone propionate (Fp) did not. DSCG suppressed the expression of
      ICAM-1, which is one of the NTHi receptors. Furthermore, DSCG exhibited an
      inhibitory effect on RSV infections. It is suggested that DSCG exerts an anti-RSV
      effect, and consequently attenuates the expression of NTHi receptors.

PMID- 19390483
TI  - Use of steroid profiling by UPLC-MS/MS as a second tier test in newborn screening
      for congenital adrenal hyperplasia: the Utah experience.
AB  - Newborn screening allows the diagnosis of congenital adrenal hyperplasia (CAH)
      before symptoms appear, preventing the severe and potentially life-threatening
      crisis associated with this disease in infancy. Traditional screening by enzyme
      immunoassay results in a large number of false positives. To reduce the number of
      unnecessary tests, anxiety to families and physicians, and the burden to the
      newborn screening follow-up program, we implemented a second-tier test for CAH
      using steroid profiling by an ultra-performance liquid chromatography-tandem mass
      spectrometry. We measured three steroids: 17-hydroxyprogesterone,
      androstenedione, and cortisol and correlated them with the age of infant at the
      time of sample collection and birth weight. Both age at collection and birth
      weight affected the levels of adrenal steroids, but the use of appropriate cut
      offs and analyte ratios allowed the identification of infants with CAH. This
      approach was effective in identifying infants with CAH, with both salt-wasting
      and simple virilizing forms, while reducing the false-positive rate from 2.6 to
      0.09%.

PMID- 19390484
TI  - Endotoxin-directed innate immunity in tracheal aspirates of mechanically
      ventilated human neonates.
AB  - Mechanical ventilation of preterm infants is associated with pulmonary
      inflammation. Intubated infants often develop bacterial tracheal colonization,
      but little is known about endotoxin in tracheal aspirates (TAs) or the
      mobilization of innate immunity toward endotoxin, a potent stimulus that
      contributes to inflammatory disease. We characterized mobilization of endotoxin
      directed innate immunity in TAs from an observational cohort of mechanically
      ventilated neonates. TA supernatants (n = 42; GA = 23-40 wk, postnatal age = 1-71
      d) were assayed for endotoxin (Limulus amoebocyte lysate assay) and endotoxin
      modulating proteins: bactericidal/ permeability-increasing protein (BPI), LPS
      binding protein (LBP), and soluble cell differentiation antigen 14 (sCD14). TA
      cellular BPI was measured by ELISA, Western blot, flow cytometry, and
      bactericidal assay. TA mRNAs encoding endotoxin-modulating proteins were measured
      by quantitative real-time PCR (qRT-PCR). Endotoxin in TA supernatants was
      proportional to both postnatal age and polymorphonuclear leukocytes (PMN).
      Neonatal TAs were rich in PMN containing BPI and expressed mRNAs encoding Toll
      like receptor (TLR) 4, CD14, and myeloid differentiation protein 2 (MD-2).
      Extracellular BPI was consistently detectable and correlated with TA PMN and GA.
      Both extracellular- and cellular-BPI increased during the first postnatal week.
      TA extracellular BPI, LBP, and sCD14 were positively correlated. TAs from
      intubated neonates demonstrate endotoxin accumulation and mobilization of
      endotoxin-directed innate immunity, potentially contributing to pulmonary
      inflammation.

PMID- 19390486
TI  - Induction of Wnt5a-expressing mesenchymal cells adjacent to the cloacal plate is
      an essential process for its proximodistal elongation and subsequent anorectal
      development.
AB  - Anorectal malformations encompass a broad spectrum of congenital defects and are
      related to the development of the genital tubercle, including the cloacal plate
      and urorectal septum. To explore the cellular and molecular basis of anorectal
      malformations, we analyzed the pathogenetic process using two mouse models:
      Danforth's short tail (Sd) and all-trans retinoic acid (ATRA)-treated mice.
      Embryologically, the cloacal plate may be divided into distal and proximal parts,
      with the distal part subdivided into ventral and dorsal parts. In the two mouse
      models, anorectal malformations occur due to improper development of the proximal
      part of the cloacal plate. At 10.5 days postcoitus (dpc), in Sd homozygotes,
      there was a lack of Shh expression only in the cloacal plate and the endoderm
      around the cloacal plate. In addition, Wnt5a was not expressed in the mesoderm
      adjacent to the cloacal plate in the two mouse models, and Axin2, which is
      regulated by Wnt signaling, was not expressed in the dorsal part of the cloacal
      plate at 12.5 dpc. Based on these results, we suggest that Wnt5a, which is
      downstream of Shh signaling, and Axin2 affect the development of the proximal
      part of the cloacal plate.

PMID- 19390485
TI  - Changes in hepatic cell junctions structure during experimental necrotizing
      enterocolitis: effect of EGF treatment.
AB  - Necrotizing enterocolitis (NEC) is a devastating disease of premature babies.
      Previously, we have shown that EGF reduces NEC and that overproduction of hepatic
      TNF-alpha is associated with intestinal damage. Leakage of TNF-alpha may be a
      consequence of epithelial hepatic cellular junction dysfunction. The aim of this
      study was to investigate changes in the composition of hepatic tight junctions
      (TJs) and adherens junctions (AJs). Using an established rat model of NEC,
      animals were divided into the following groups: dam fed (DF), formula fed (NEC),
      or fed with formula supplemented with EGF (EGF). Serum EGF and histologic
      localization of major TJ and AJ proteins were evaluated. Distribution patterns of
      hepatic TJ and AJ proteins were significantly altered in the NEC group compared
      with those in DF or EGF groups. Cytoplasmic accumulation of occludin, claudin-2,
      and ZO-1 with reduction of claudin-3 signal was detected in the liver of NEC
      rats. Localization of beta-catenin was associated with the hepatocyte membrane in
      EGF and DF groups, but diffused in the NEC group. These data show that hepatic
      cellular junctions are significantly altered during NEC pathogenesis. EGF
      mediated reduction of experimental NEC is associated with protection of hepatic
      integrity and structure.

PMID- 19390488
TI  - Memory B cell function in HIV-infected children-decreased memory B cells despite
      ART.
AB  - B cell dysfunction is a well-studied complication of HIV infection in adults.
      Data on B cell differentiation in normal and HIV-infected children are lacking.
      We show the distribution of B cell subsets and immunoglobulin levels in HIV
      infected children compared with controls. Furthermore, we observe the long-term B
      cell reconstitution of vaccine-specific immunity after antiretroviral therapy
      (ART). Phenotype of B cells (naive, non-switched memory, switched memory) was
      analyzed in 48 infected children and 62 controls. In nine HIV-infected children,
      functional reconstitution was quantified by tetanus-specific antibodies and by
      performing a lymphocyte transformation test (LTT) in a longitudinal approach.
      Switched memory B cells are significantly reduced in HIV-infected children.
      Vaccine-specific antibodies and response to LTT increase after initiation of ART.
      Our data indicate a significant dysfunction in the B cell system, despite
      effective ART. Partial reconstitution of humoral immunity may have therapeutic
      implications in a subset of HIV-infected children.

PMID- 19390487
TI  - Chronic in utero cyclooxygenase inhibition alters PGE2-regulated ductus
      arteriosus contractile pathways and prevents postnatal closure.
AB  - Although prostaglandin E2 (PGE2) vasodilates the ductus arteriosus, tocolysis
      with cyclooxygenase (COX) inhibitors delays postnatal ductus arteriosus closure.
      We used fetal mice and sheep to determine whether PGE2 has a role in the
      development of ductus contractility that is distinct from its function as a
      vasodilator. Prolonged exposure of fetal ductus to PGE2 in vitro increased the
      expression of CaL- and K+-channel genes (CaLalpha1c, CaLbeta2, Kir6.1, and Kv1.5,
      which regulate oxygen-induced constriction) without affecting the genes that
      regulate Rho-kinase-mediated calcium sensitization. Conversely, chronic exposure
      to COX inhibitors in utero decreased expression of CaL- and K+-channel genes,
      without affecting Rho-kinase-associated genes. Chronic COX inhibition in utero
      decreased the ductus' in vitro contractile response to stimuli that use CaL- and
      K+-channels (like O2 and K+), whereas the response to stimuli that act through
      Rho-kinase-mediated pathways (like U46619) was not significantly affected.
      Phosphodiesterase expression, which decreases the ductus' sensitivity to cAMP- or
      cGMP-dependent vasodilators, was increased by PGE2 exposure and decreased by COX
      inhibition, respectively. These studies identify potential downstream effectors
      of a PGE2-mediated, developmental program, regulating oxygen-induced ductus
      closure. Alterations in these effectors may explain the increased risk of patent
      ductus arteriosus (PDA) after in utero COX inhibition.

PMID- 19390489
TI  - Distinct roles of TLR4 and CD14 in LPS-induced inflammatory responses of
      neonates.
AB  - During infections, pathogens bind to toll-like receptor (TLR)4 and CD14 receptors
      and induce cytokine release, leading to inflammation. Here, we investigated TLR4
      and CD14 expression on peripheral blood leukocytes (PBLs) and their roles in
      lipopolysaccharide (LPS)-induced cytokine and chemokine release. Full-term and
      preterm neonates and adults were studied. PBLs were pretreated with anti-TLR4-
      and anti-CD14-blocking antibodies and stimulated with LPS. Cytokine and chemokine
      levels were measured in supernatants. TLR4, CD14 expression, and LPS-induced
      CXCL8 release were higher in neonates, possibly contributing to aberrant
      inflammation. TLR4 blockade resulted in approximately 3-fold greater suppression
      of LPS-induced CXCL8 release in preterm neonates (38%) than in adults (14%). CD14
      blockade (approximately 80%) in neonates induced approximately 3-fold greater
      inhibition of CXCL8 release, compared with anti-TLR4 (approximately 30%). Anti
      TLR4 partly (50-60%) inhibited IL-10 and TNF-alpha, whereas anti-CD14 completely
      suppressed their release. Our findings reveal that neonates depend more on TLR4
      for CXCL8 release. Furthermore, neonatal LPS-induced CXCL8 release, apart from
      TLR4/CD14-mediated signaling, is regulated by LPS interactions with other TLRs
      and/or immune receptors. IL-10 and TNF-alpha release depends on LPS binding not
      only to CD14/TLR4 but also to CD14 associated with another TLR. Our findings
      reveal the contribution of TLR4 and CD14 in neonatal cytokine and chemokine
      release and could aid in design of antagonists to prevent harmful inflammation.

PMID- 19390490
TI  - Hypoxic-ischemic encephalopathy in preterm infants: antecedent factors, brain
      imaging, and outcome.
AB  - Our objectives were to establish antecedent factors and patterns of brain injury
      and their prognostic value in preterm infants with hypoxic-ischemic
      encephalopathy (HIE). Essential inclusion criteria were gestation (GA) < or =36
      wk, Apgar scores <5/<7 at 1/5 min, major resuscitation at birth, and a brain MRI
      <6 postnatal wk. At least one additional criterion was required of the following:
      abnormal intrapartum CTG, sentinel event, meconium, cord pH <7.0, neonatal
      seizures, and multiorgan failure. Antenatal and perinatal data and > or =2 y
      neurodevelopmental outcome were documented. Fifty-five infants (GA 26-36; median,
      35 wk) were eligible; all had 1-6 (median, 3) additional criteria. Placental
      abruption was the commonest identifiable antecedent event. Evidence of infection
      was not prominent. Main sites of injury were basal ganglia (BG, 75%), mostly
      severe, white matter (WM, 89%), mostly mild, brainstem (44%), and cortex (58%).
      Brainstem injury was associated with severe BG, WM, and cortical injury. Two-year
      outcome: death (32%), cerebral palsy (26%, mostly severe quadriplegia), mild
      impairment (10%), and normal (32%). Significant central gray matter and brainstem
      injury was found in many preterm infants with HIE. Neonatal MRI findings allowed
      accurate prediction of neurodevelopmental outcome. Early MRI is feasible and a
      valuable tool in this poorly reported group of infants.

PMID- 19390491
TI  - Oxygen toxicity and reactive oxygen species: the devil is in the details.
AB  - Reactive oxygen species (ROS) serve as cell signaling molecules for normal
      biologic processes. However, the generation of ROS can also provoke damage to
      multiple cellular organelles and processes, which can ultimately disrupt normal
      physiology. An imbalance between the production of ROS and the antioxidant
      defenses that protect cells has been implicated in the pathogenesis of a variety
      of diseases, such as cancer, asthma, pulmonary hypertension, and retinopathy. The
      nature of the injury will ultimately depend on specific molecular interactions,
      cellular locations, and timing of the insult. This review will outline the
      origins of endogenous and exogenously generated ROS. The molecular, cellular,
      pathologic, and physiologic targets will then be discussed with a particular
      emphasis on aspects relevant to child development. Finally, antioxidant defenses
      that scavenge ROS and mitigate associated toxicities will be presented, with a
      discussion of potential therapeutic approaches for the prevention and/or
      treatment of human diseases using enzymatic and nonenzymatic antioxidants.

PMID- 19390492
TI  - Paternal allele of IGF2 gene haplotype CTG is associated with fetal and placental
      growth in Japanese.
AB  - IGF-II associates with feto-placental growth in rodent and human. We determined
      three tag-single nucleotide polymorphisms (SNPs) to investigate haplotype
      frequency of IGF2 relative to size at birth in 134 healthy Japanese infants. In
      addition, a total of 276 healthy infants were investigated to determine whether
      common genetic variation of IGF2 might contribute to feto-placental growth using
      haplotype analysis. Further, quantitative methylation analysis of the IGF2/H19
      was performed using the MassARRAY Compact system. In the initial study, the
      frequency of haplotype CTG from the paternal allele in small for date (SFD)
      infants was significantly higher than that in non-SFD infants (p = 0.03). In a
      second study, the CTG haplotype infants exhibited significantly lower birth
      length, weight, and placental weight compared with non-CTG infants. Further, the
      number of infants less than -1.5 SD (SD) birth weight in CTG haplotype was higher
      than those in non-CTG infants. There was no significant difference in the
      methylation status of H19/IGF2 in the two haplotypes. In conclusion, inheriting
      the IGF2 CTG haplotype from a paternal allele results in reduced feto-placental
      growth, but it is not associated with the methylation status of IGF2/H19.

PMID- 19390493
TI  - Exposure to uteroplacental insufficiency reduces the expression of signal
      transducer and activator of transcription 3 and proopiomelanocortin in the
      hypothalamus of newborn rats.
AB  - IUGR has been linked to the development of type 2 diabetes. Recent data suggest
      that some of the molecular defects underlying type 2 diabetes reside in the CNS.
      Disruption of the signal transducer and activator of transcription 3 (STAT3) in
      the hypothalamic neurons expressing leptin receptor, results in severe obesity,
      hyperglycaemia, and hyperinsulinemia. Our aim was to investigate the expression
      of STAT3 and its downstream effector proopiomelanocortin (POMC) in IUGR rats
      obtained by uterine artery ligation. On day 19 of gestation, time-dated Sprague
      Dawley pregnant rats were anesthetized, and both the uterine arteries were
      ligated. At birth, hypothalamus was dissected and processed to evaluate the
      expression of STAT3, its phosphorylated form, and POMC. STAT3 mRNA, STAT3
      protein, phosphorylated STAT3, POMC mRNA, and POMC protein were significantly
      reduced in IUGR versus sham animals (p < 0.0001, p < 0.05 and p < 0.001, p <
      0.01, p < 0.01, respectively). No significant differences either in serum leptin
      concentrations or in hypothalamic leptin receptor expression were observed. Our
      results suggest that an abnormal intrauterine milieu can affect the hypothalamic
      expression of STAT3 and POMC at birth, altering the hypothalamic signaling
      pathways that regulate the energy homeostasis.

PMID- 19390494
TI  - Staphylococcus epidermidis isolated from newborn infants express pilus-like
      structures and are inhibited by the cathelicidin-derived antimicrobial peptide
      LL37.
AB  - Coagulase-negative staphylococci and its subtype Staphylococcus epidermidis are
      major indigenous Gram-positive inhabitants of the human skin. Colonization occurs
      in direct connection with birth and terrestrial adaptation. This study focuses on
      factors that may influence skin colonization of the newborn infant that relates
      to the immune status of both the bacteria and the host. Skin is an effective
      barrier against bacteria, and this function is partly mediated by the presence of
      antimicrobial peptides including human cathelicidin peptide LL37. Gram-positive
      bacteria have been described to have adhesive pili on their surface that mediates
      specific attachment to the host. Here, we identify, by negative staining
      transmission electron microscopy (EM), two different types of pilus-like
      structures commonly expressed on S. epidermidis isolated from newborn infants. We
      also show that the cathelicidin antimicrobial peptide LL37, constitutively
      expressed in the skin barrier of the newborn, significantly inhibited growth of
      S. epidermidis indicating its importance for the ecological stability of the skin
      microbiota. Further studies are required to elucidate molecular mechanisms of
      host-microbe interactions, both for the maintenance of a mutually beneficial
      homeostatic relationship and for the protection of self when it results in overt
      disease.

PMID- 19390495
TI  - Human papilloma virus DNA detection, p53 and Ki67 expression in penile verrucous
      and squamous cell carcinomas in the same patient.

PMID- 19390497
TI  - Drugs for rheumatoid arthritis.

PMID- 19390496
TI  - Evidence of underreporting of adverse childhood experiences, San Francisco
      municipal STD clinic, 2007.

PMID- 19390498
TI  - The preventive and therapeutic impact of antiplatelet agents: past and present.
AB  - Already more than two thousands years ago the Greek physician Hippocrates (V-IV
      century B.C.) used the extracts of the willow bark to fight fever. At the end of
      the eighteen hundreds the German chemist Felix Hoffmann obtained acetylsalicylic
      acid in stable and pure form, and from then on Aspirin (where A is the
      abbreviation of acetyl and Spir stands for Spirsaure, the German name of
      salicylic acid) has had enormous diffusion. In 1953 Lawrence Craven reported that
      he had successfully prescribed aspirin to hundreds of adult male patients for the
      non-specific prophylaxis of coronary thrombosis. Aspirin is now one of the most
      well-known drugs in the world, and in the last decades a large body of scientific
      evidence has appeared with regard to the preventive and therapeutic effects of
      aspirin and those of other antiplatelet agents. In fact, antiplatelet agents
      constitute a cornerstone in current pharmacological treatment and prophylaxis.
      Among the most interesting recent and beneficial areas of impact of aspirin and
      of other antiplatelet drugs, there are those of stroke and of coronary artery
      disease, and today targeted pharmacological and non-pharmacological interventions
      should be carefully combined to deal, preventively and therapeutically, with the
      cardiovascular epidemic.

PMID- 19390499
TI  - Atrial fibrillation and congestive heart failure.
AB  - Atrial fibrillation (AF) and congestive heart failure (CHF) are commonly
      encountered together, either condition predisposing to the other. The presence of
      each condition increases the morbidity and mortality associated with the other
      and their coexistence complicates patient management. Common risk factors include
      age, hypertension, diabetes mellitus and coronary artery disease. This article
      addresses the complex interplay between AF and CHF with regards to shared
      mechanisms, effects on prognosis, management issues and available,
      pharmacological and non-pharmacological therapeutic options.

PMID- 19390500
TI  - Atrial fibrillation in the elderly.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and its
      prevalence is increasing with age. With aging of the population treatment of
      atrial fibrillation especially in elderly population is a growing task for all
      medical staff working with elderly patients. Treatment of atrial fibrillation
      especially in elderly patients has to focus on prevention of thromboembolism as
      well as symptom relief with rate or rhythm control. This review article will
      focus on medical and non-pharmacological treatment options for the treatment of
      atrial fibrillation in elderly patients.

PMID- 19390501
TI  - Epicardial catheter ablation of atrial fibrillation.
AB  - Catheter ablation for atrial fibrillation, while superior to medical therapy
      alone, carries significant risk of complications and limited efficacy. Surgical
      therapy for atrial fibrillation, including the maze procedure, seems to be more
      effective but is also more invasive than percutaneous approaches. In this review,
      we outline the rationale for a percutaneous catheter-based epicardial ablation
      strategy. Operators considering such a procedure should have a detailed
      understanding of the anatomy of the pericardial space, which is reviewed in this
      manuscript. Also, technology used in epicardial ablation and special challenges
      of epicardial ablation are discussed. Finally, some preliminary work on
      epicardial ablation of atrial fibrillation is reviewed before concluding with
      some possibilities for future research in the area.

PMID- 19390502
TI  - Clinical outcomes and complications of enteral nutrition among older adults.
AB  - AIM: Several reviews or clinical trials published in the last years have not
      demonstrated that tube feeding can improve outcomes, including inhalation
      pneumonia, survival, pressure sores. Further, high rate of risks are recognized.
      Therefore, this practice should be discouraged for severely demented patients.
      The aim of this study was to assess the validity of these findings in a sanitary
      district in the Venetian Region, Italy, characterized by a fully integrated
      program of territorial-hospital care and where enteral nutrition (EN) is
      supervised by a specialized nutritional team (NT). METHODS: A distinctive aspect
      of this study concerns the fact that all patients with tube feeding were followed
      at home, in hospital, in nursing home by the same NT. The team controls the
      selection of patients and supports the follow-up, according to the guidelines of
      the Italian Society of Parenteral and Enteral nutrition. The study provides a
      prospective evaluation including 108 patients, mean age 78.2 years, followed for
      12 months. Each patient underwent multidimensional tests, including activities of
      daily living, instrumental activities of daily living, Norton, Pfeiffer and
      Karnofsky scales, and anthropometric and biochemical indicators of nutritional
      status. RESULTS: The main diagnoses were dementia (72 patients), stroke (23
      patients), malignancy (5 patients), amyotrophic lateral sclerosis (3 patients)
      and miscellaneous disease (5 patients). EN was delivered by PEG (62 patient), NGT
      (45 patient), jejunostomy in one patient. The main complications of nasogastric
      tube versus PEG have been inhalation 15.5% and 7.9%, respectively, tube
      displacement 62.2%, and 4.7%, tube clogging 11.1% and 7.9 %. The first month
      mortality rate was 7.4% and 23.1% at one year. The mean survival was 674 days.
      CONCLUSIONS: Almost all complications have been mild and could be managed
      throughout adequately. Their prevalence is low, with reference to the long period
      of follow-up, for a whole of 39420 days. Tube displacement is frequent with NGT
      but not with PEG and may be a cause of physical restraint, compromising in this
      way patient's quality of life. In this study, survival was nearly three times
      higher than reported in literature. These positive outcomes may be the result of
      two factors. First, the selection and follow-up program was supervised by the
      same nutritional team. Second, the network of integrated services of continuing
      care, including nursing homes, hospital and home care.

PMID- 19390503
TI  - Infectious aortitis and spondylodiscitis in patients with endovascular stents.
AB  - The infection of endovascular stents remains one of the most problematic
      complications of aortic surgery. This article describes the case of a 61-year-old
      male with ascendant and descendent aorta endovascular stents, hospitalized for
      pyrexia, weight loss and back pain. Blood culture was positive for Staphylococcus
      hominis resistant to oxacillin and ciprofloxacin. Spiral computed tomography,
      magnetic resonance imaging and leukocyte-labelled scintigraphy showed that the
      patient developed a perigraft infection which spondylodiscitis in correspondence
      of D7, D8 and D9 vertebras. The biopsy CT-scan guided of vertebral inflammed
      tissue revealed a coagulase-negative Staphylo-coccus and the presence of numerous
      neutrophilis granulocytes. The reintervention for substituting an infected graft
      was excluded due to the high risk of death or paraplegia. A therapy with
      vancomycin, rifampicin and ceftazidime was started. On the basis of clinical and
      radiological findings, it was decided to switch empirical antimicrobial therapy
      to levofloxacin, minocycline and teicoplanin and a reduction of inflammation
      indices was observed. The patient was discharged maintaining this chronic
      suppressive antimicrobial therapy with a 28-day cycle of linezolid with complete
      regression of pain, and normalization of inflammation blood indices. After,
      therapy switched to teicoplanin three times a week while maintaining good
      clinical and radiological features. In the present, due to the high risk in
      performing a surgical procedure, a conservative chronic suppressive antimicrobial
      therapy with teicoplanin allowed to control the infection on an outpatient basis,
      thereby reducing the costs.

PMID- 19390504
TI  - Analysis of a flawed double-blind, placebo-controlled, clinical trial of patients
      claimed to have persistent Lyme disease following treatment.

PMID- 19390505
TI  - Work-related fatalities associated with tree care operations--United States, 1992
      2007.
AB  - Workers in various industries and occupations are involved in the care and
      maintenance of trees, such as tree trimming, pruning, and removal. This work is
      recognized as having many safety hazards. Although previous analyses have
      involved subgroups of workers who perform this type of work, no analysis has
      focused on identifying injured workers from all industries and occupations that
      perform tree care operations. This report summarizes the characteristics of fatal
      occupational injuries, using data from the Census of Fatal Occupational Injuries
      (CFOI) and a case series of fatality investigations conducted by CDC's National
      Institute for Occupational Safety and Health (NIOSH) Fatality Assessment and
      Control Evaluation (FACE) program. During 1992--2007, a total of 1,285 workers
      died while performing tree care and maintenance; 44% were trimming or pruning a
      tree when fatally injured. The most common causes of death were being struck by
      or against an object (42% of deaths), most commonly a tree or branch; falls to a
      lower level (34%); and electrocutions (14%). Most of the decedents (57%) worked
      for small establishments with 10 or fewer employees. Employers, trade and worker
      associations, and policymakers should take additional steps to improve the safety
      of workers involved in tree care, such as providing formal training to workers
      and ensuring that personal protective equipment (e.g., fall protection equipment)
      is used properly.

PMID- 19390506
TI  - Malignant mesothelioma mortality--United States, 1999-2005.
AB  - Malignant mesothelioma is a fatal cancer primarily associated with exposure to
      asbestos. The latency period between first exposure to asbestos and clinical
      disease usually is 20--40 years. Although asbestos is no longer mined in the
      United States, the mineral is still imported, and a substantial amount of
      asbestos remaining in buildings eventually will be removed, either during
      remediation or demolition. Currently, an estimated 1.3 million construction and
      general industry workers potentially are being exposed to asbestos. To
      characterize mortality attributed to mesothelioma, CDC's National Institute for
      Occupational Safety and Health (NIOSH) analyzed annual multiple-cause-of-death
      records for 1999--2005, the most recent years for which complete data are
      available. For those years, a total of 18,068 deaths of persons with malignant
      mesothelioma were reported, increasing from 2,482 deaths in 1999 to 2,704 in
      2005, but the annual death rate was stable (14.1 per million in 1999 and 14.0 in
      2005). Maintenance, renovation, or demolition activities that might disturb
      asbestos should be performed with precautions that sufficiently prevent exposures
      for workers and the public. In addition, physicians should document the
      occupational history of all suspected and confirmed mesothelioma cases.

PMID- 19390507
TI  - HIV Infection--Guangdong Province, China, 1997-2007.
AB  - In 2007, an estimated 700,000 persons in China were living with human
      immunodeficiency virus (HIV) infection. An estimated 50,000 new HIV infections
      and 20,000 deaths related to acquired immunodeficiency syndrome (AIDS) occurred
      in 2007, and an estimated 71% of persons with HIV infection were unaware of their
      HIV status. In 2007, 40.6% of those living with HIV had been infected through
      heterosexual transmission and 38.1% through injection-drug use. Guangdong
      Province in southeastern China is the country's most populous province, with an
      estimated 75.6 million permanent residents and 16.5 million migrants; the
      province has undergone rapid economic development. Since 1986, a case-based
      surveillance system (CBSS) in China has collected data on persons infected with
      HIV, including demographic characteristics and transmission categories. To assess
      recent trends in HIV infection in the province, the Guangdong Center for Disease
      Control, with technical assistance from CDC, analyzed CBSS data for the period
      1997--2007. The results of that analysis indicated that the number of HIV cases
      increased from 102 in 1997 to 4,593 in 2007, although this increase resulted, in
      part, from expanded testing and surveillance. Among males classified by HIV
      transmission category, 82.1% of newly diagnosed infections were attributed to
      injection-drug use. Among females classified by HIV transmission category, 53.7%
      engaged in high-risk heterosexual conduct. Despite substantial methodologic
      limitations, these results can be useful to Guangdong public health agencies in
      targeting and evaluating HIV prevention, care, and treatment programs.

PMID- 19390508
TI  - Swine influenza A (H1N1) infection in two children--Southern California, March
      April 2009.
AB  - On April 17, 2009, CDC determined that two cases of febrile respiratory illness
      occurring in children who resided in adjacent counties in southern California
      were caused by infection with a swine influenza A (H1N1) virus. The viruses from
      the two cases are closely related genetically, resistant to amantadine and
      rimantadine, and contain a unique combination of gene segments that previously
      has not been reported among swine or human influenza viruses in the United States
      or elsewhere. Neither child had contact with pigs; the source of the infection is
      unknown. Investigations to identify the source of infection and to determine
      whether additional persons have been ill from infection with similar swine
      influenza viruses are ongoing. This report briefly describes the two cases and
      the investigations currently under way. Although this is not a new subtype of
      influenza A in humans, concern exists that this new strain of swine influenza A
      (H1N1) is substantially different from human influenza A (H1N1) viruses, that a
      large proportion of the population might be susceptible to infection, and that
      the seasonal influenza vaccine H1N1 strain might not provide protection. The lack
      of known exposure to pigs in the two cases increases the possibility that human
      to-human transmission of this new influenza virus has occurred. Clinicians should
      consider animal as well as seasonal influenza virus infections in their
      differential diagnosis of patients who have febrile respiratory illness and who
      1) live in San Diego and Imperial counties or 2) traveled to these counties or
      were in contact with ill persons from these counties in the 7 days preceding
      their illness onset, or 3) had recent exposure to pigs. Clinicians who suspect
      swine influenza virus infections in a patient should obtain a respiratory
      specimen and contact their state or local health department to facilitate testing
      at a state public health laboratory.

PMID- 19390509
TI  - High-resolution video tracking of locomotion in adult Drosophila melanogaster.
AB  - Flies provide an important model for studying complex behavior due to the
      plethora of genetic tools available to researchers in this field. Studying
      locomotor behavior in Drosophila melanogaster relies on the ability to be able to
      quantify changes in motion during or in response to a given task. For this
      reason, a high-resolution video tracking system, such as the one we describe in
      this paper, is a valuable tool for measuring locomotion in real-time. Our
      protocol involves the use of an initial air pulse to break the flies momentum,
      followed by a thirty second filming period in a square chamber. A tracking
      program is then used to calculate the instantaneous speed of each fly within the
      chamber in 10 msec increments. Analysis software then compiles this data, and
      outputs a variety of parameters such as average speed, max speed, time spent in
      motion, acceleration, etc. This protocol will discuss proper feeding and
      management of flies for behavioral tasks, handling flies without anesthetization
      or immobilization, setting up a controlled environment, and running the assay
      from start to finish.

PMID- 19390510
TI  - D3 dopamine receptor regulation of ETB receptors in renal proximal tubule cells
      from WKY and SHRs.
AB  - BACKGROUND: The dopaminergic and endothelin systems, by regulating sodium
      transport in the renal proximal tubule (RPT), participate in the control of blood
      pressure. The D(3) and ETB receptors are expressed in RPTs, and D(3) receptor
      function in RPTs is impaired in spontaneously hypertensive rats (SHRs).
      Therefore, we tested the hypothesis that D(3) receptors can regulate ETB
      receptors, and that D(3) receptor regulation of ETB receptors in RPTs is impaired
      in SHRs. METHODS: ETB receptor expression in RPT cells was measured by
      immunoblotting and reverse transcriptase-PCR and ETB receptor function by
      measuring Na(+)-K(+) ATPase activity. D(3)/ETB receptor interaction was studied
      by co-immunoprecipitation. RESULTS: In Wistar-Kyoto (WKY) RPT cells, the D(3)
      receptor agonist, PD128907, increased ETB receptor protein expression, effects
      that were blocked by removal of calcium in the culture medium. The stimulatory
      effect of D(3) on ETB receptor mRNA and protein expression was also blocked by
      nicardipine. In contrast, in SHR RPT cells, PD128907 decreased ETB receptor
      expression. Basal D(3)/ETB receptor co-immunoprecipitation was three times
      greater in WKY than in SHRs. The absolute amount of D(3)/ETB receptor co
      immunoprecipitation induced by a D(3) receptor agonist was also greater in WKY
      than in SHRs. Stimulation of ETB receptors decreased Na(+)-K(+) ATPase activity
      in WKY but not in SHR cells. Pretreatment with PD128907 augmented the inhibitory
      effect of BQ3020 on Na(+)-K(+) ATPase activity in WKY but not in SHR cells.
      CONCLUSIONS: D(3) receptors regulate ETB receptors by physical receptor
      interaction and govern receptor expression and function. D(3) receptor regulation
      of ETB receptors is aberrant in RPT cells from SHRs.

PMID- 19390511
TI  - The effects of ethnic discrimination and socioeconomic status on endothelin-1
      among blacks and whites.
AB  - BACKGROUND: Ethnic disparities in cardiovascular disease (CVD) may partially
      reflect differences in chronic stress burden that vary by social class and
      exposure to ethnic discrimination. Stress is associated with increased endothelin
      1 (ET-1). This study examined the relationship of ET-1 to socioeconomic status
      (SES) and to perceived ethnic discrimination among black (n = 51) and white (n =
      65) adults (mean age 36.5). METHODS: The Perceived Discrimination subscale of the
      Scale of Ethnic Experience measured exposure to discrimination and the
      Hollingshead Two-Factor Index of Social Position assessed SES. Plasma ET-1 was
      sampled upon awakening after an overnight admission. RESULTS: SES and ET-1 levels
      were similar across ethnic groups, but mean discrimination scores were higher
      among blacks than whites (P < 0.001). Multiple regressions found that the SES x
      ethnicity interaction was associated with ET-1 (P < 0.05), after adjustment for
      gender, resting mean arterial pressure (MAP), body mass index (BMI), and exercise
      frequency. Regressions stratified by ethnicity revealed that lower SES correlated
      with higher ET-1 in whites (P < 0.001), but not blacks, and accounted for 21% of
      the variance. Another series of regressions revealed an interaction effect of
      ethnicity by discrimination on ET-1 (P < 0.05). Increased discrimination
      correlated with increased ET-1 among blacks (P < 0.05), but not whites, and
      explained 11% of the variance after adjustment for SES, gender, exercise
      frequency, and socially desirable response bias. CONCLUSIONS: Thus, ET-1 levels
      increased in association with different psychosocial burdens in blacks and
      whites. Plasma ET-1 was higher among whites with lower SES and among blacks with
      higher levels of perceived ethnic discrimination, regardless of SES.

PMID- 19390512
TI  - Insular cortex atrophy as an independent determinant of disrupted diurnal rhythm
      of ambulatory blood pressure in elderly hypertension.
AB  - BACKGROUND: Insular cortex (Ic) has been suggested to be a key site in limbic
      autonomic integration. Association of Ic damage with disruption of diurnal blood
      pressure (BP) variation and higher serum level of noradrenaline has been
      reported. We examined the relationships of Ic volume with ambulatory BP measures
      and noradrenaline concentration. METHODS: Ambulatory BP monitoring and brain
      magnetic resonance imaging (MRI) were performed in 55 elderly never-treated
      hypertensives. Ic volumes were measured using an intensity contour mapping
      algorithm. Serum adrenaline and noradrenaline concentrations were evaluated.
      RESULTS: Subjects were classified into an Ic-atrophy group (n = 14) and non-Ic
      atrophy group (n = 41) based on a total Ic volume (left and right side) of 12.6
      cm(3) (lowest quartile). In the Ic-atrophy group, 24 h (145 mm Hg vs. 134 mm Hg,
      P < 0.05) and sleep (143 mm Hg vs. 127 mm Hg, P < 0.01) systolic BP (SBP) and
      nocturnal SBP dipping (1.30% vs. 8.54%, P < 0.05) were significantly different,
      and noradrenaline (373 pg/ml vs. 296 pg/ml, P = 0.08) was marginally different
      from those in the non-Ic-atrophy group. Left Ic volume was significantly
      correlated with 24 h (r = -0.277) and sleep (r = -0.499) SBP and nocturnal SBP
      dipping (r = 0.413), while right Ic volume was significantly correlated with 24 h
      (r = -0.261) and sleep (r = -0.430) SBP, nocturnal SBP dipping (r = 0.321) and
      noradrenaline (r = -0.335). In multiple linear regression analysis adjusted for
      age, gender and body mass index (BMI), left Ic volume was significantly
      negatively associated with sleep SBP (P < 0.01) and positively with nocturnal SBP
      dipping (P < 0.05). CONCLUSION: Ic atrophy, specifically in the left side, may
      partly contribute to disruption of diurnal ambulatory BP rhythm via central
      autonomic nervous system (ANS) dysregulation.

PMID- 19390514
TI  - Association of blood pressure with left ventricular mass in untreated
      hypertensives in rural Yunnan Province.
AB  - BACKGROUND: Chinese rural residents make up one-eighth of the world's population.
      Hypertension (HTN) and its resultant cardiovascular complications are rapidly
      increasing in this vast segment of humanity, while its treatment and control
      remain unacceptably low. HTN is associated with increased left ventricular mass
      (LVM), but the magnitude and characteristics of this relationship in persons not
      undergoing treatment are unknown. METHODS: We studied 344 randomly selected
      adults who were not being treated for HTN and who had ages between 50 and 70
      years (mean age 57.8, 51.7% female) using a questionnaire, height, weight, blood
      pressure (BP), and ultrasonic measurements of LVM. We performed bivariate and
      multivariable regression analysis to examine the relation of BP with LVM index
      (LVMI). RESULTS: We found a HTN prevalence of 30%. There was a significant (P <
      0.0001) linear relationship between BP and LVMI in this untreated population.
      Diastolic (DBP) compared to systolic BP (SBP) was more strongly associated with
      LVMI (beta = 0.714 vs. 0.379, both P = 0.02). Persons with vs. without HTN had
      higher LVMI (102.5 g vs. 84.9 g, P < 0.0001). CONCLUSIONS: The LVMI of
      hypertensives, not undergoing treatment in rural Yunnan province is strongly
      related to BP, especially DBP.

PMID- 19390513
TI  - Soluble tumor necrosis factor receptor 1 level is associated with left
      ventricular hypertrophy: the northern Manhattan study.
AB  - BACKGROUND: Although inflammatory markers may be associated with risk of
      cardiovascular events, few data are available regarding these markers and their
      association with left ventricular hypertrophy (LVH). We sought to evaluate
      whether inflammatory markers were independently associated with LVH in a
      multiethnic population in northern Manhattan. METHODS: A population-based cross
      sectional study was conducted in 660 participants without stroke, who had
      undergone both transthoracic echocardiography and testing for soluble tumor
      necrosis factor receptor (sTNFR) 1, interleukin (IL)-6, and high-sensitivity C
      reactive protein (hsCRP). LV mass was calculated according to an established
      formula. LVH was defined as LV mass >90th percentile of the participants.
      RESULTS: The mean age was 67.4 +/- 8.8 years, 35.5% were men, 61.7% were
      Hispanic, 19.7% were black, and 18.6% were white. In univariate analyses, hsCRP,
      IL-6, and sTNFR1 were significantly associated with LV mass. Multiple linear
      regression analyses demonstrated that sTNFR1 (P = 0.0008) was associated with LV
      mass after adjusting for demographic and medical risk factors, but hsCRP and IL-6
      were not. When all markers were included in the same model, sTNFR1 remained
      significant, but hsCRP and IL-6 did not. Compared with the lowest quartile of
      sTNFR1, those in the highest quartile were more likely to have LVH (odds ratio =
      1.84, 95% confidence interval, 0.97-3.64, P = 0.06). CONCLUSIONS: sTNFR1, but not
      hsCRP nor IL-6, is independently associated with increased LV mass. Chronic
      subclinical inflammation including the TNFR1-associated system may contribute to
      LVH.

PMID- 19390515
TI  - Trends and disparities in provider diagnosis of overweight analysis of NHANES
      1999-2004.
AB  - Rates of overweight and obesity are disproportionately high within minority
      populations. This study examined the trends in provider diagnosis of overweight
      from 1999 to 2004 and examined whether there were differences in provider
      diagnosis based on race/ethnicity. We examined data from 4,071 adults with BMI
      >or=30 who participated in the National Health and Nutrition Examination Surveys
      (NHANES) (1999-2004). Provider diagnosis was determined by self-report. From 1999
      to 2004, the provider diagnosis of overweight decreased from 71 to 64% (P =
      0.003). After controlling for potential confounders, non-Hispanic blacks and
      Mexican Americans were less likely to report a provider diagnosis of overweight
      compared to non-Hispanic whites. Odds ratio (OR) (95% confidence interval (CI))
      for non-Hispanic blacks was 0.6 (95% CI, 0.4-0.8) and for Mexican Americans was
      0.7 (95% CI, 0.4-1.0) compared to non-Hispanic whites. Reasons for this disparity
      warrant further investigation.

PMID- 19390516
TI  - High energy digestion efficiency and altered lipid metabolism contribute to
      obesity in BFMI mice.
AB  - To constitute a valuable resource to identify individual genes involved in the
      development of obesity, a novel mouse model, the Berlin Fat Mouse Inbred line 860
      (BFMI860), was established. In order to characterize energy intake and energy
      expenditure in obese BFMI860 mice, we performed two independent sets of
      experiments in male BFMI860 and B6 control mice (10 per line). In experiment 1,
      we analyzed body fat content noninvasively by dual-energy X-ray absorptiometry
      and measured resting metabolic rate at thermoneutrality (RMRt) and respiratory
      quotient (RQ) in week 6, 10, and 18. In a second experiment, energy digested
      (energy intake minus fecal energy loss) was determined by bomb calorimetry from
      week 6 through week 12. BFMI860 mice were heavier and had higher fat mass (final
      body fat content was 24.7% compared with 14.6% in B6). They also showed fatty
      liver syndrome. High body fat accumulation in BFMI860 mice was restricted to
      weeks 6-10 and was accompanied by hyperphagia, higher energy digestion, higher
      RQs, and abnormally high blood triglyceride levels. Lean mass-adjusted RMRt was
      not altered between lines. These results indicate that in BFMI860 mice, the
      excessive accumulation of body fat is associated with altered lipid metabolism,
      high energy intake, and energy digestion. Assuming that BFMI860 mice and their
      obese phenotypes are of polygenic nature, this line is an excellent model for the
      study of obesity in humans, especially for juvenile obesity and hyperlipidemia.

PMID- 19390517
TI  - Diet and exercise interventions reduce intrahepatic fat content and improve
      insulin sensitivity in obese older adults.
AB  - Both obesity and aging increase intrahepatic fat (IHF) content, which leads to
      nonalcoholic fatty liver disease (NAFLD) and metabolic abnormalities such as
      insulin resistance. We evaluated the effects of diet and diet in conjunction with
      exercise on IHF content and associated metabolic abnormalities in obese older
      adults. Eighteen obese (BMI >or=30 kg/m(2)) older (>or=65 years old) adults
      completed a 6-month clinical trial. Participants were randomized to diet (D
      group; n = 9) or diet + exercise (D+E group; n = 9). Primary outcome was IHF
      quantified by magnetic resonance spectroscopy (MRS). Secondary outcomes included
      insulin sensitivity (assessed by oral glucose tolerance), body composition
      (assessed by dual-energy X-ray absorptiometry), physical function (VO(2 peak) and
      strength), glucose, lipids, and blood pressure (BP). Body weight (D: -9 +/- 1%,
      D+E: -10 +/- 2%, both P < 0.05) and fat mass (D: -13 +/- 3%, D+E -16 +/- 3%, both
      P < 0.05) decreased in both groups but there was no difference between groups.
      IHF decreased to a similar extent in both groups (D: -46 +/- 11%, D+E: -45 +/-
      8%, both P < 0.05), which was accompanied by comparable improvements in insulin
      sensitivity (D: 66 +/- 25%, D+E: 68 +/- 28%, both P < 0.05). The relative
      decreases in IHF correlated directly with relative increases in insulin
      sensitivity index (ISI) (r = -0.52; P < 0.05). Improvements in VO(2 peak),
      strength, plasma triglyceride (TG), and low-density lipoprotein-cholesterol
      concentration, and diastolic BP occurred in the D+E group (all P < 0.05) but not
      in the D group. Diet with or without exercise results in significant decreases in
      IHF content accompanied by considerable improvements in insulin sensitivity in
      obese older adults. The addition of exercise to diet therapy improves physical
      function and other obesity- and aging-related metabolic abnormalities.

PMID- 19390518
TI  - Changes in health state utilities with changes in body mass in the Diabetes
      Prevention Program.
AB  - Health utilities are measures of health-related quality of life (HRQL) used in
      cost-effectiveness research. We evaluated whether changes in body weight were
      associated with changes in health utilities in the Diabetes Prevention Program
      (DPP) and whether associations differed by treatment assignment (lifestyle
      intervention, metformin, placebo) or baseline obesity severity. We constructed
      physical (PCS-36) and mental component summary (MCS-36) subscales and short-form
      6D (SF-6D) health utility index for all DPP participants completing a baseline 36
      item short form (SF-36) HRQL assessment (N = 3,064). We used linear regression to
      test associations between changes in body weight and changes in HRQL indicators,
      while adjusting for other demographic and behavioral variables. Overall
      differences in HRQL between treatment groups were highly statistically
      significant but clinically small after 1 year. In multivariable models, weight
      change was independently associated with change in SF-6D score (increase of 0.007
      for every 5 kg weight loss; P < 0.001), but treatment effects independent of
      weight loss were not. We found no significant interaction between baseline
      obesity severity and changes in SF-6D with changes in body weight. However,
      increases in physical function (PCS-36) with weight loss were greater in persons
      with higher baseline obesity severity. In summary, improvements in HRQL are
      associated with weight loss but not with other effects of obesity treatments that
      are unrelated to weight loss. Although improvements in the SF-6D did not exceed
      commonly reported thresholds for a minimally important difference (0.04), these
      changes, if causal, could still have a significant impact on clinical cost
      effectiveness estimates if sustained over multiple years.

PMID- 19390519
TI  - Ethnic differences in subcutaneous adiposity and waist girth in children and
      adolescents.
AB  - The purpose of this study was to examine ethnic differences in adiposity as
      measured by sum of skinfolds (SKF) and waist circumference (WC) in children and
      adolescents, after statistical adjustment for the BMI and age. A cross sectional
      sample of 3,218 (55% white, 49% male) children and adolescents aged 5-18 years
      who participated in the Bogalusa Heart Study (1992-1994) were included in these
      analyses. Sex-specific ANOVAs, adjusted for BMI and age, for each 2-year age
      group compared measures of adiposity (SKF and WC) between ethnic groups. No
      significant differences in the proportions of children and adolescents who were
      overweight and obese by ethnicity or sex were found. Mean SKF in normal weight (P
      < 0.0001) and overweight (P < 0.0001) categories was higher for white than black
      children of both sexes. Across most age categories, white boys and girls had
      significantly higher SKF than black boys and girls, respectively (P <or= 0.05).
      Across most age categories, white boys had significantly higher WC than black
      boys (P <or= 0.05) with no difference in the girls, when adjusted for BMI and
      age. Measures of adiposity in childhood and adolescence were significantly higher
      in white children compared to black children, when adjusted for BMI and age.
      Throughout childhood and adolescence, white boys and girls had higher SKF and
      white boys had higher WC. Differences in adiposity between ethnic groups should
      be considered in disease risk assessment and stratification as they are observed
      even for a given BMI level.

PMID- 19390520
TI  - Associations between perceived weight discrimination and the prevalence of
      psychiatric disorders in the general population.
AB  - Despite the increased prevalence of weight discrimination, few studies have
      examined the association between perceived weight discrimination and the
      prevalence of current psychiatric disorders in the general population. This study
      utilized a subsample of overweight and obese individuals (N = 22,231) from Wave 2
      of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC),
      a cross-sectional nationally representative study of noninstitutionalized US
      adults. Perceived weight discrimination is associated with substantial
      psychiatric morbidity and comorbidity. These results remained significant after
      adjusting for a potential confound, perceived stress. Moreover, social support
      did not buffer against the adverse effects of perceived weight discrimination on
      mental health. Controlling for BMI did not diminish the associations, indicating
      that perceived weight discrimination is potentially harmful to mental health
      regardless of weight. These results highlight the urgent need for a multifaceted
      approach to address this important public health issue, including interventions
      to assist overweight individuals in coping with the mental health sequelae of
      perceived weight discrimination.

PMID- 19390521
TI  - Are obesity and physical activity clustered? A spatial analysis linked to
      residential density.
AB  - The aim of this study was to examine spatial clustering of obesity and/or
      moderate physical activity and their relationship to a neighborhood's built
      environment. Data on levels of obesity and moderate physical activity were
      derived from the results of a telephone survey conducted in 2006, with 1,863
      survey respondents in the study sample. This sample was spread across eight
      suburban neighborhoods in Metro Vancouver. These areas were selected to contrast
      residential density and income and do not constitute a random sample, but within
      each area, respondents were selected randomly. Obesity and moderate physical
      activity were mapped to determine levels of global and local spatial
      autocorrelation within the neighborhoods. Clustering was measured using Moran's I
      at the global level, Anselin's Local Moran's I at the local level, and
      geographically weighted regression (GWR). The global-level spatial analysis
      reveals no significant clustering for the attributes of obesity or moderate
      physical activity. Within individual neighborhoods, there is moderate clustering
      of obesity and/or physical activity but these clusters do not achieve statistical
      significance. In some neighborhoods, local clustering is restricted to a single
      pair of respondents with moderate physical activity. In other neighborhoods, any
      moderate local clustering is offset by negative local spatial autocorrelation.
      Importantly, there is no evidence of significant clustering for the attribute of
      obesity at either the global or local level of analysis. The GWR analysis fails
      to improve significantly upon the global model-thus reinforcing the negative
      results. Overall, the study indicates that the relationship between the urban
      environment and obesity is not direct.

PMID- 19390522
TI  - Influence of BMI on health-related quality of life: comparison between an obese
      adult cohort and age-matched population norms.
AB  - The aim of this study was to determine health-related quality of life and fatigue
      measures in obese subjects and to compare scores with age- and gender-matched
      population norms. A total of 163 obese subjects were recruited from laparoscopic
      adjustable gastric banding or exercise and diet weight loss programs between
      March 2006 and December 2007. All subjects completed the Medical Outcomes Study
      Short Form 36 (SF-36), Assessment of Quality of Life (AQoL), and Multidimensional
      Assessment of Fatigue (MAF) questionnaires. One-sample t-tests were used to
      compare transformed scores with age- and gender-matched population norms and
      controls. Obese subjects have significantly lower SF-36 physical and emotional
      component scores, significantly lower AQoL utility scores and significantly
      higher fatigue scores compared to age-matched population norms. Within the study
      cohort, the SF-36 physical functioning, role physical and bodily pain scores, and
      AQoL utility index were even lower in subjects with clinical knee osteoarthritis
      (OA). However, obese individuals without OA still had significantly lower scores
      compared to population norms. Obesity is associated with impaired health-related
      quality of life and disability as measured by the SF-36, AQoL, and fatigue score
      (MAF) compared to matched population norms.

PMID- 19390524
TI  - BMI and rates of suicide in the United States: an ecological analysis.
AB  - BMI has been inversely associated with risk of completed suicide in several
      cohort studies, but putative mechanisms for this association and its
      generalizability throughout the United States are uncertain. We ascertained
      recent population-based, state-level data on rates of obesity, completed suicide
      (by method), firearm ownership, smoking, major depression, income, education,
      white race, and nonmetropolitan residence, compiled from federal agencies and
      surveys, and determined the adjusted population-weighted correlations of
      statewide obesity rates with measures of completed and attempted suicide.
      Statewide prevalence of obesity was strongly inversely correlated with age
      adjusted suicide rate (multivariable-adjusted r=-0.66; P<0.001). The correlation
      was somewhat stronger for rates of nonfirearm-related (r=-0.75; P<0.001) than
      firearm-related suicides (r=-0.53; P<0.001), and was of similar magnitude as the
      positive correlations of firearm prevalence with suicide rate (r=0.75; P<0.001)
      or of obesity with prevalence of diabetes (r=0.41; P=0.006). In analyses of fatal
      and nonfatal suicidal acts, obesity rates were inversely correlated with rates of
      suicidal acts using firearms (r=-0.53; P=0.02) and suffocation (r=-0.76; P<0.001)
      but not other methods. Obesity rates were also inversely correlated with the case
      fatality ratios of acts using poisoning (r=-0.51; P=0.01). Thus, statewide rates
      of obesity are strongly inversely correlated with rates of completed suicide in
      multivariable analyses, a finding that appears to relate to fewer attempts by
      suffocation and a lower case-fatality ratio for poisonings, although the
      mechanism for the inverse correlation with firearm-related suicides requires
      further elucidation.

PMID- 19390523
TI  - Interplay between weight loss and gut microbiota composition in overweight
      adolescents.
AB  - The aim of this study was to determine the influence of an obesity treatment
      program on the gut microbiota and body weight of overweight adolescents. Thirty
      six adolescents (13-15 years), classified as overweight according to the
      International Obesity Task Force BMI criteria, were submitted to a calorie
      restricted diet (10-40%) and increased physical activity (15-23 kcal/kg body
      weight/week) program over 10 weeks. Gut bacterial groups were analyzed by
      quantitative real-time PCR before and after the intervention. A group of subjects
      (n=23) experienced >4.0 kg weight loss and showed significant BMI (P=0.030) and
      BMI z-score (P=0.035) reductions after the intervention, while the other group
      (n=13) showed <2.0 kg weight loss. No significant differences in dietary intake
      were found between both groups. In the whole adolescent population, the
      intervention led to increased Bacteroides fragilis group (P=0.001) and
      Lactobacillus group (P=0.030) counts, and to decreased Clostridium coccoides
      group (P=0.028), Bifidobacterium longum (P=0.031), and Bifidobacterium
      adolescentis (P=0.044) counts. In the high weight-loss group, B. fragilis group
      and Lactobacillus group counts also increased (P=0.001 and P=0.007,
      respectively), whereas C. coccoides group and B. longum counts decreased (P=0.001
      and P=0.044, respectively) after the intervention. Total bacteria, B. fragilis
      group and Clostridium leptum group, and Bifidobacterium catenulatum group counts
      were significantly higher (P<0.001-0.036) while levels of C. coccoides group,
      Lactobacillus group, Bifidobacterium, Bifidobacterium breve, and Bifidobacterium
      bifidum were significantly lower (P<0.001-0.008) in the high weight-loss group
      than in the low weight-loss group before and after the intervention. These
      findings indicate that calorie restriction and physical activity have an impact
      on gut microbiota composition related to body weight loss, which also seem to be
      influenced by the individual's microbiota.

PMID- 19390525
TI  - Low or moderate dietary energy restriction for long-term weight loss: what works
      best?
AB  - Theoretical calculations suggest that small daily reductions in energy intake can
      cumulatively lead to substantial weight loss, but experimental data to support
      these calculations are lacking. We conducted a 1-year randomized controlled pilot
      study of low (10%) or moderate (30%) energy restriction (ER) with diets differing
      in glycemic load in 38 overweight adults (mean +/- s.d., age 35 +/- 6 years; BMI
      27.6 +/- 1.4 kg/m(2)). Food was provided for 6 months and self-selected for 6
      additional months. Measurements included body weight, resting metabolic rate
      (RMR), adherence to the ER prescription assessed using (2)H(2)(18)O, satiety, and
      eating behavior variables. The 10%ER group consumed significantly less energy (by
      (2)H(2)(18)O) than prescribed over 12 months (18.1 +/- 9.8%ER, P = 0.04), while
      the 30%ER group consumed significantly more (23.1 +/- 8.7%ER, P < 0.001). Changes
      in body weight, satiety, and other variables were not significantly different
      between groups. However, during self-selected eating (6-12 months) variability in
      % weight change was significantly greater in the 10%ER group (P < 0.001) and
      poorer weight outcome on 10%ER was predicted by higher baseline BMI and greater
      disinhibition (P < 0.0001; adj R(2) = 0.71). Weight loss at 12 months was not
      significantly different between groups prescribed 10 or 30%ER, supporting the
      efficacy of low ER recommendations. However, long-term weight change was more
      variable on 10%ER and weight change in this group was predicted by body size and
      eating behavior. These preliminary results indicate beneficial effects of low
      level ER for some but not all individuals in a weight control program, and
      suggest testable approaches for optimizing dieting success based on
      individualizing prescribed level of ER.

PMID- 19390526
TI  - Sedentariness at work: how much do we really sit?
AB  - Sedentariness is associated with obesity. We examined whether people with
      sedentary jobs are equally inactive during their work days and leisure days. We
      enrolled 21 subjects of varying weight and body fat (11 men:10 women, 38 +/- 8
      years, 83 +/- 17 kg, BMI 28 +/- 5 kg/m(2), 29 +/- 11 fat kg, 35 +/- 9% fat). All
      subjects continued their usual work and leisure-time activities whilst we
      measured daily activity and body postures for 10 days. The data supported our
      hypothesis that people sit more at work compared to leisure (597 +/- 122 min/day
      cf 484 +/- 83 min/day; P < 0.0001). The mean difference was 110 +/- 99 min/day.
      Similarly, work days were associated with less standing (341 +/- 97 min/day; P =
      0.002) than leisure days (417 +/- 101 min/day). Although the walking bouts did
      not differ significantly between work and leisure (46 +/- 9 vs. 42 +/- 9 walking
      bouts/day); the mean free-living velocity of a walk at work was 1.08 +/- 0.28 mph
      and on leisure days was 0.94 +/- 0.24 mph (P = 0.03) and the average time spent
      walking was 322 +/- 91 min on work days and 380 +/- 108 min on leisure days (P =
      0.03). Estimates of the daily energetic cost of walking approximated 527 +/- 220
      kcal/day for work days and 586 +/- 326 kcal/day for leisure days (r = 0.72, P <
      0.001). Work days are associated with more sitting and less walking/standing time
      than leisure days. We suggest a need to develop approaches to free people from
      their chairs and render them more active.

PMID- 19390527
TI  - Neutrophil activation in morbid obesity, chronic activation of acute
      inflammation.
AB  - Recent studies show that morbid obesity is associated with activation of the
      innate immune response. Neutrophil activation is a fundamental process in the
      innate immune response. Therefore, the activation state of neutrophils in
      severely obese subjects and the effect of bariatric surgery on neutrophil
      activation was evaluated. Neutrophil activation was assessed by measuring
      circulating concentrations of myeloperoxidase (MPO) and calprotectin in 37
      severely obese and 9 control subjects (enzyme-linked immunosorbent assay).
      Moreover, membrane expression of CD66b on circulating neutrophils was measured
      using flow cytometry in a group of seven severely obese and six control subjects.
      Immunohistochemical detection of MPO was performed in adipose and muscle tissue.
      Plasma MPO and calprotectin levels were significantly increased in severely obese
      subjects as compared to healthy controls, 27.1 +/- 10.8 vs. 17.3 +/- 5.5 ng/ml (P
      < 0.001) and 115.5 +/- 43.5 vs. 65.1 +/- 23.1 ng/ml (P < 0.001) for MPO and
      calprotectin, respectively. In line, CD66b expression was significantly increased
      in severely obese individuals, 177.3 +/- 43.7 vs. 129.7 +/- 9.2 (mean
      fluorescence intensity) (P < 0.01). Bariatric surgery resulted in decreased
      calprotectin, but MPO plasma levels remained elevated. Adipose and muscle tissue
      did not contain increased numbers of MPO expressing cells in severely obese
      individuals. These results point out that circulating neutrophils are activated
      to a greater extent in severely obese subjects. Our data support the finding that
      the innate immune system is activated in severely obese individuals. Moreover,
      because neutrophils have a short life span, this indicates that the chronic
      inflammatory condition associated with morbid obesity is characterized by a
      continuous activation of the innate immune system.

PMID- 19390528
TI  - Crystallizing membrane proteins using lipidic mesophases.
AB  - A detailed protocol for crystallizing membrane proteins that makes use of lipidic
      mesophases is described. This has variously been referred to as the lipid cubic
      phase or in meso method. The method has been shown to be quite general in that it
      has been used to solve X-ray crystallographic structures of prokaryotic and
      eukaryotic proteins, proteins that are monomeric, homo- and hetero-multimeric,
      chromophore-containing and chromophore-free, and alpha-helical and beta-barrel
      proteins. Its most recent successes are the human-engineered beta(2)-adrenergic
      and adenosine A(2A) G protein-coupled receptors. Protocols are provided for
      preparing and characterizing the lipidic mesophase, for reconstituting the
      protein into the monoolein-based mesophase, for functional assay of the protein
      in the mesophase and for setting up crystallizations in manual mode. Methods for
      harvesting microcrystals are also described. The time required to prepare the
      protein-loaded mesophase and to set up a crystallization plate manually is about
      1 h.

PMID- 19390529
TI  - Phylogenetic classification and identification of bacteria by mass spectrometry.
AB  - Bacteria are a convenient source of intrinsic marker proteins, which can be
      detected efficiently by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry. The patterns of protein masses observed can be used for
      accurate classification and identification of bacteria. Key to the reliability of
      the method is a robust and standardized procedure for sample preparations,
      including bacterial culturing, chemical treatment for bacterial cell wall
      disruption and for protein extraction, and mass spectrometry analysis. The
      protocol is an excellent alternative to classical microbiological classification
      and identification procedures, requiring minimal sample preparation efforts and
      costs. Without cell culturing, the protocol takes in general <1 h.

PMID- 19390530
TI  - Marker selection for genetic case-control association studies.
AB  - Association studies can focus on candidate gene(s), a particular genomic region,
      or adopt a genome-wide association approach, each of which has implications for
      marker selection. The strategy for marker selection will affect the statistical
      power of the study to detect a disease association and is a crucial element of
      study design. The abundant single nucleotide polymorphisms (SNPs) are the markers
      of choice in genetic case-control association studies. The genotypes of
      neighboring SNPs are often highly correlated ('in linkage disequilibrium', LD)
      within a population, which is utilized for selecting specific 'tagSNPs' to serve
      as proxies for other nearby SNPs in high LD. General guidelines for SNP selection
      in candidate genes/regions and genome-wide studies are provided in this protocol,
      along with illustrative examples. Publicly available web-based resources are
      utilized to browse and retrieve data, and software, such as Haploview and
      Goldsurfer2, is applied to investigate LD and to select tagSNPs.

PMID- 19390531
TI  - Practitioners' perspectives and experiences of the new National Health Service
      dental contract.
AB  - BACKGROUND: In April 2006, fundamental changes were made to the arrangements for
      commissioning state funded (National Health Service, NHS) dental care in England
      and Wales. These involved the dissolution of a universal national contract and
      the introduction of locally commissioned primary dental care services. Suggested
      advantages included the elimination of a fee-for-item 'treadmill', an increased
      emphasis on prevention and improved patient access. This change came at a time
      when many practitioners were opting to provide care outside the NHS. OBJECTIVES:
      This study investigated dentists' experience of the new contract and compared
      this with attitudes determined in a previous survey of the same cohort of
      dentists conducted immediately before the changed commissioning arrangements.
      METHODS: Data were collected via a postal questionnaire, comprising a combination
      of 60 open and closed questions, mailed to 608 general dental practitioners in
      Wales. RESULTS: Four hundred and ninety-six (77%) questionnaires were returned.
      Four hundred and seventeen practitioners continued to provide NHS dental care.
      Only 46 (11%) of the 417 practitioners agreed that they liked the new method of
      remuneration and the majority (362 [86.8%]) perceived that they still delivered
      state-funded care in a 'treadmill' environment. This compares with 34.9% of
      dentists who perceived the new system as a 'treadmill' immediately before its
      implementation. Three hundred and forty-eight (83.4%) disagreed that they were
      able to spend more time on prevention and 356 (85.3%) did not feel they had more
      time to spend with patients--key objectives of the reforms. Two hundred and
      seventy-five (65.9%) respondents agreed that local NHS commissioners were
      controlling their business. CONCLUSION: This survey, conducted 18 months after
      the implementation of the new commissioning arrangements, suggests that
      practitioners are deeply unhappy with local commissioning. It raises questions as
      to whether the changes have achieved the Government's stated objectives in
      reforming state-funded primary dental care.

PMID- 19390532
TI  - Axin localizes to the centrosome and is involved in microtubule nucleation.
AB  - Axin is known to have an important role in the degradation of beta-catenin in the
      Wnt pathway. Here, we reveal a new function of Axin at the centrosome. Axin was
      localized to the centrosome in various cell lines and formed a complex with gamma
      tubulin. Knockdown of Axin reduced the localization of gamma-tubulin and gamma
      tubulin complex protein 2-components of the gamma-tubulin ring complex-to the
      centrosome and the centrosomal microtubule nucleation activity after treatment
      with nocodazole. These phenotypes could not be rescued by the reduction in the
      levels of beta-catenin. Although the expression of Axin rescued these phenotypes
      in Axin-knockdown cells, overexpression of Axin2, which is highly homologous to
      Axin, could not. Axin2 was also localized to the centrosome, but it did not form
      a complex with gamma-tubulin. These results suggest that Axin, but not Axin2, is
      involved in microtubule nucleation by forming a complex with gamma-tubulin at the
      centrosome.

PMID- 19390533
TI  - G-protein signalling negatively regulates the stability of aryl hydrocarbon
      receptor.
AB  - Aryl hydrocarbon receptor (AhR) is a transcription factor that works as a dioxin
      receptor and is also involved in various physiological phenomena, including
      development and cell proliferation. Here, we show that the Galpha13 signal
      destabilizes AhR by promoting the ubiquitination of AhR. Galpha13 interacts
      directly with AhR-interacting protein (AIP) and inhibits the interaction between
      AhR and AIP, a crucial interacting protein of AhR. Strikingly, a reporter gene
      assay and a quantitative reverse transcription-PCR analysis indicate that the
      Galpha13 signal shows a potent inhibitory effect on the ligand-induced
      transcriptional activation of AhR. Galpha13 results in the nuclear translocation
      of AhR in a ligand-independent manner. However, in the presence of active
      Galpha13, AhR fails to form the active transcriptional complex. Taken together,
      we propose a new negative regulation of dioxin signalling by the G protein.

PMID- 19390534
TI  - The association of a simple blood pressure-independent parameter derived from
      ambulatory blood pressure variability with short-term mortality.
AB  - We explored the predictive ability of the blood pressure variability ratio
      (BPVR), defined as the ratio of 24-h ambulatory systolic blood pressure
      variability to diastolic variability, and evaluated its predictable relation with
      blood pressure and the Ambulatory Arterial Stiffness Index (AASI). A total of
      3433 consecutive patients were followed up to 16 years for all-cause mortality.
      Blood pressure variability was expressed by the standard deviation. BPVR, which
      is the systolic-on-diastolic slope estimated by a known type of symmetric
      regression ('reduced major axis'), was compared with other expressions of this
      slope and with AASI using other regression procedures. Time-dependent Cox
      proportional hazard models, adjusted for demographics, 24-h mean blood pressure,
      24-h pulse pressure and dipping were used to assess the association of BPVR and
      slope-related parameters with all-cause mortality. We found that Pearson's
      correlation between BPVR and the symmetric slope was 0.957, and between 1-1/BPVR
      (an AASI-equivalent expression) and the symmetric version of AASI was 0.973. BPVR
      was entirely independent of mean arterial pressure (r=0.013). Systolic and
      diastolic ambulatory blood pressure variability was not significantly associated
      with mortality. Over 16 years, BPVR predicted all-cause mortality [hazard
      ratio=1.21 (95% CI 1.05-1.40) per 1 s.d. increase]. In time-dependent models,
      increased BPVR was strongly associated with an 18-month mortality, weakly related
      to 7 years mortality, showing no effect thereafter. Thus, the ratio between 24-h
      systolic and diastolic blood pressure variability, readily available from
      ambulatory monitoring reports, is an easy-to-calculate systolic-on-diastolic
      slope. It is a blood pressure-independent measure believed to express an arterial
      property, with prognostic power similar to that of AASI.

PMID- 19390535
TI  - Effects of candesartan and amlodipine on cardiovascular events in hypertensive
      patients with chronic kidney disease: subanalysis of the CASE-J Study.
AB  - We examined the effects of candesartan and amlodipine on cardiovascular events in
      hypertensive patients with chronic kidney disease (CKD) using the data from the
      Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial. CKD was
      defined as proteinuria and/or decreased GFR (<60 ml per min per 1.73 m(2)) at
      enrollment. Among 2720 subjects with CKD, there were 1376 and 1344 patients in
      the candesartan and the amlodipine group, respectively. During a 3.2-year follow
      up, cardiovascular event rate did not differ in the two groups (7.2% for
      candesartan and 7.6% for amlodipine). In the subgroup analysis based on the CKD
      stage, there were no significant differences in the incidence rates of
      cardiovascular events between the two groups in stages 1+2 and 3 CKD. In stage 4
      CKD, however, candesartan reduced the incidence of cardiovascular events (55%
      risk reduction), particularly of renal events (81% risk reduction), compared with
      amlodipine. Furthermore, composite cardiovascular events were increased as the
      CKD stage progressed, and this effect was exaggerated in the presence of
      proteinuria. Finally, the new onset of diabetes was less in the candesartan-based
      regimen in stage 3 CKD. In conclusion, candesartan protected hypertensive
      patients with CKD more potently against renal events, particularly in moderately
      to-severely impaired CKD. Furthermore, candesartan prevented a new onset of
      diabetes in CKD, which would be favorable for the long-term management of CKD.

PMID- 19390536
TI  - The expression of ATP-binding cassette transporters in hypertensive patients.
AB  - Cholesterol efflux is regulated by cholesterol transporters, including adenosine
      triphosphate-binding cassette transporters, A1, G1 (ABCA1, ABCG1), and scavenger
      receptor class B type I (SR-BI). We have investigated whether the expression of
      these transporters/receptor is altered in patients with hypertension and also
      studied their functional effects in cholesterol efflux. The newly diagnosed
      hypertensive patients, as well as age- and gender-matched healthy controls were
      recruited. mRNA of ABCA1, ABCG1 and SR-BI in monocytes was measured. The
      functional effects of the three transporters/receptor and cholesterol efflux from
      monocyte-derived macrophages ex vivo were also determined. The expression of
      ABCA1 and ABCG1 was significantly decreased in the newly diagnosed untreated
      hypertensive patients compared with that in healthy controls. The levels of ABCA1
      and ABCG1 were negatively associated with blood pressure, and the reduction of
      ABCA1 and ABCG1 could be reversed by anti-hypertensive therapy. No significant
      associations between plasma lipids, oxidized low-density lipoprotein (LDL) and
      the expression of ABCA1 or ABCG1 were found. Cholesterol efflux from monocyte
      derived macrophages to autologous serum, apolipoprotein AI (apoAI) or high
      density lipoprotein (HDL) was impaired in hypertensive patients. Cholesterol
      efflux to autologous serum or apoAI was associated with the expression of ABCA1,
      whereas cholesterol efflux to autologous serum or HDL was associated with the
      expression of ABCG1. The expression of ABCA1 and ABCG1 in monocytes is reduced in
      hypertensive patients, which could be reversed by anti-hypertensive therapy. The
      reduction in ABCA1/ABCG1 is associated with the impairment of cholesterol efflux
      from monocyte-derived macrophages.

PMID- 19390537
TI  - Vasopressin and hyperosmolality regulate NKCC1 expression in rat OMCD.
AB  - Secretory-type Na-K-2Cl cotransporter (NKCC1) is known to play roles in both acid
      and sodium excretion, and is more abundant in dehydration. To determine the
      mechanisms by which dehydration stimulates NKCC1 expression, the effects of
      vasopressin, oxytocin and hyperosmolality on NKCC1 mRNA and protein expressions
      in the outer medullary collecting duct (OMCD) of rats were investigated using RT
      competitive PCR and western blot analysis. Microdissected OMCD was incubated in
      isotonic or hypertonic solution, or with AVP or oxytocin for 60 min at 37 degrees
      C. Hyperosmolality induced by NaCl, mannitol or raffinose increased NKCC1 mRNA
      expression in OMCD by 130-240% in vitro. The stimulation of NKCC1 mRNA expression
      by NaCl was highest at 690 mosmol kg(-1) H(2)O and gradually decreased at higher
      osmolalities. The incubation of OMCD with AVP (10(-7) M) for 60 min increased
      NKCC1 mRNA expression by 100%. The administration of AVP to rats for 4 days using
      an osmotic mini-pump also increased NKCC1 mRNA and protein expressions in OMCD by
      130%. In contrast, oxytocin (10(-7) M) did not stimulate the NKCC1 mRNA
      expression in OMCD in vitro. Chronic injection of oxytocin increased the NKCC1
      mRNA expression by 36%. These data showed that hyperosmolality and vasopressin
      stimulate NKCC1 mRNA and protein expressions in rat OMCD. It is concluded that
      NKCC1 expression is regulated directly and indirectly by vasopressin.

PMID- 19390538
TI  - Time-released garlic powder tablets lower systolic and diastolic blood pressure
      in men with mild and moderate arterial hypertension.
AB  - Numerous clinical investigations that have focused on the hypotensive effects of
      garlic-based preparations have led to controversial results that may be partially
      because of differences in the composition of the preparations and in the
      biological responses they induce. It is possible that garlic powder tablets with
      a prolonged mode of action could induce more potent biological effects. In this
      double-blind, placebo-controlled trial with an active control arm, the
      hypotensive action of time-released garlic powder tablets (Allicor) was compared
      with that of regular garlic pills (Kwai) in 84 men with mild or moderate arterial
      hypertension. After an 8-week placebo treatment run-in phase, patients were
      randomized either to 600 mg Allicor (n=30) or to placebo (n=20) daily for 8
      weeks. In addition, in the open-label branch, patients received either 2400 mg
      Allicor daily (n=18) or 900 mg Kwai daily (n=16). Allicor treatment (600 mg
      daily) resulted in a reduction of both systolic and diastolic blood pressures by
      7.0 mm Hg (95% confidence interval (95% CI): 5.3-8.7) and 3.8 mm Hg (95% CI: 2.7
      4.8), respectively. Increasing the Allicor dosage to 2400 mg daily did not
      provide any additional benefit. Treatment with Kwai resulted in the same decrease
      in systolic blood pressure (5.4 mm Hg, 95% CI: 1.9-8.8) as that seen with
      Allicor, but no decrease in diastolic blood pressure was observed with Kwai.
      Different effects of Allicor and Kwai on diastolic blood pressure may be because
      of the prolonged action of Allicor, which allows better bioavailability of the
      vasoactive constituents of garlic powder. The results of this study show that
      time-released garlic powder tablets are more effective for the treatment of mild
      and moderate arterial hypertension than are regular garlic supplements.

PMID- 19390539
TI  - Haplotype-based case-control study of the human CYP4F2 gene and essential
      hypertension in Japanese subjects.

PMID- 19390540
TI  - The association between masked hypertension and waist circumference as an obesity
      related anthropometric index for metabolic syndrome: the Ohasama study.
AB  - Masked hypertension has been proven to be associated with an increased risk for
      cardiovascular diseases. The purpose of this study was to examine the direct
      associations of obesity-related anthropometric indices, including waist
      circumference, with masked hypertension. Participants in this population-based
      survey included 395 residents (> or = 35 years) of Ohasama, a rural Japanese
      community. They measured blood pressure at home (HBP) and underwent an oral
      glucose-tolerance test. Participants were classified into four groups on the
      basis of their HBP and casual-screening blood pressure (CBP) values: sustained
      normotension, white-coat hypertension, masked hypertension or sustained
      hypertension. The relationships between the obesity-related anthropometric
      indices and the four blood pressure groups were examined using multivariate
      analysis adjusted for confounding factors. The mean waist circumference in men
      was significantly higher in individuals with masked hypertension (87.3 cm) than
      in those with sustained normotension (81.0 cm) and white-coat hypertension (79.3
      cm), whereas the mean waist circumference in women was significantly higher in
      individuals with sustained hypertension (79.5 cm) than in those with sustained
      normotension (75.0 cm). In the multivariate analysis, waist circumference, body
      mass index (BMI) and waist-to-hip ratio were significantly associated with masked
      hypertension, particularly in individuals with normal CBP. Our results suggest
      that HBP measurements might be particularly important in abdominally obese people
      for the early detection of masked hypertension.

PMID- 19390541
TI  - The relationship between antihypertensive combination therapies comprising
      diuretics and/or beta-blockers and the risk of new-onset diabetes: a
      retrospective longitudinal cohort study.
AB  - We investigate the associations of antihypertensive drugs in double and triple
      combination regimens comprising diuretics and/or beta-blockers on the development
      of new-onset diabetes (NOD). This study was a retrospective cohort study carried
      out using data from claim forms provided to the central regional branch of the
      Bureau of National Health Insurance (BNHI) in Taiwan from January 2001 to
      December 2006. We estimated the odds ratios (ORs) of NOD associated with
      antihypertensive combination therapy use; non-NOD individuals served as the
      reference group. A total of 2361 NOD cases were identified among the 12,386
      hypertensive patients (6143 men and 6243 women, aged 28-86 years (mean age:
      68+11)) during the study period. The risk of NOD was higher after adjusting for
      age and sex among users of double combinations of diuretics plus beta-blockers
      (adjusted OR, 1.25; 95% confidence interval (CI): 1.12-1.58), diuretics plus
      calcium channel blockers (CCBs; adjusted OR: 1.14; 95% CI: 1.06-1.26) and beta
      blockers plus calcium channel blockers (adjusted OR: 1.12; 95% CI: 1.04-1.29)
      than that among non-users. Patients who took angiotensin-converting enzyme (ACE)
      inhibitors, or alpha-blockers as part of a double-drug regimen were at a lower
      risk of developing NOD than were non-users. Double- or triple-drug combinations
      comprising angiotensin receptor blockers (ARBs) and vasodilators were not
      associated with risk of NOD. The results of this study suggest that users of
      double-drug combination therapies containing diuretics and/or beta-blockers and
      an ACE inhibitor or alpha-blocker are at a significantly lower risk of developing
      NOD than are other classes.

PMID- 19390542
TI  - Effectiveness of open-label losartan/hydrochlorothiazide combination therapy in
      Asian patients with hypertension not controlled with ACE inhibitor or ARB
      monotherapy.
AB  - Antihypertensive efficacy and safety of losartan/hydrochlorothiazide (HCTZ)
      combinations have not been adequately studied in Asians. In this open-label, 12
      week study in seven Asian areas, patients on monotherapy with angiotensin
      receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) but
      not at blood pressure (BP) goal (sitting diastolic BP (SiDBP) <90 mm Hg in non
      diabetics and <80 mm Hg in diabetics) were switched to losartan 50 mg/HCTZ 12.5
      mg. At 4 and 8 weeks, the therapy for patients not at goal BP was titrated to
      losartan 100 mg/HCTZ 12.5 mg and to losartan 100 mg/HCTZ 25 mg, respectively.
      Data analysis included 430 patients with mean (s.d.) age 53.0 (10.1) years and
      51.9% of the female gender. After 8 weeks (primary end point; titration up to
      losartan 100 mg/HCTZ 12.5 mg), 73.5% (95% confidence interval (CI): 69.0-77.6) of
      patients reached BP goal; 63.4 and 78.1% of patients reached BP goal at 4 weeks
      (titration up to losartan 50 mg/HCTZ 12.5 mg) and at 12 weeks (titration up to
      losartan 100 mg/HCTZ 25 mg). The mean changes from baseline (95% CI) in sitting
      systolic BP and SiDBP at 8 weeks were -16.7 (-18.0 to -15.4) mm Hg and -12.1 (
      12.9 to -11.4) mm Hg, respectively. Clinical and laboratory adverse experiences
      (AEs) were reported in 27.5 and 21.0% of patients, respectively. Nine patients
      were discontinued because of drug-related clinical AEs. Switching Asian patients
      currently not at BP goal with ARB or ACEI monotherapy to a losartan/HCTZ
      combination achieved BP goal in the majority of patients. Losartan/HCTZ
      combinations were generally well tolerated.

PMID- 19390543
TI  - Diabetes mellitus accelerates left ventricular diastolic dysfunction through
      activation of the renin-angiotensin system in hypertensive rats.
AB  - Diabetes mellitus (DM) is a major risk factor for heart failure, independent of
      coronary artery disease or hypertension (HT). Therefore, our study was designed
      to examine the mechanisms of DM-induced left ventricular (LV) diastolic
      dysfunction. In this study, we made five different 10-week treatment groups of
      Dahl salt-sensitive rats as follows: Control; a low-salt (0.5% NaCl) diet, HT; a
      high-salt (5% NaCl) diet, DM; a low-salt diet with streptozotocin (STZ) injection
      (30 mg kg(-1) i.p.), HT+DM; a high-salt diet with STZ injection, and the
      Olmesartan group; a high-salt diet with STZ treated with an angiotensin receptor
      blocker, olmesartan (1 mg kg(-1) day(-1)). Cardiac diastolic dysfunction with a
      preserved systolic function was noted in the HT group, and was most prominently
      noted in the HT+DM group, characterized by enhanced cardiac fibrosis, whereas the
      extent of HT and myocardial hypertrophy was comparable between the two groups.
      Myocardial expressions of collagen III, transforming growth factor-beta2,
      angiotensin-converting enzyme (ACE), angiotensin II type-1 receptor and
      myocardial oxidative stress (evaluated by 4-hydroxy-2-nonenal-modified protein)
      were mostly enhanced in the HT+DM group. Importantly, there was a positive
      correlation between the extent of diastolic dysfunction and that of myocardial
      ACE expression. All these cardiac abnormalities induced by DM and HT were
      ameliorated in the olmesartan group. These results indicate that DM accelerates
      diastolic dysfunction in hypertensive heart disease through activation of the
      renin-angiotensin system, with subsequent inflammatory and oxidative stresses and
      myocardial fibrosis, suggesting that an inhibition of the system is effective for
      the treatment of diastolic dysfunction in this combined disorder.

PMID- 19390544
TI  - The struggles of cancer centers.

PMID- 19390545
TI  - Hematology: Lenalidomide plus dexamethasone is effective in multiple myeloma.
AB  - A prospective subgroup analysis of two prospective, randomized, double-blind,
      placebo-controlled phase III clinical trials showed that the combination of
      lenalidomide plus dexamethasone is superior to dexamethasone alone in patients
      with relapsed or refractory multiple myeloma who had been previously treated with
      thalidomide; the implications for clinical practice are discussed.

PMID- 19390546
TI  - Medical Oncology: IROX as second-line therapy for metastatic colorectal cancer.
AB  - Haller et al. demonstrated that irinotecan plus oxaliplatin (IROX) is more
      efficacious than irinotecan alone after fluoropyrimidine failure in advanced
      colorectal cancer. IROX does not change, but enriches the treatment algorithm of
      advanced colorectal cancer at the second-line level.

PMID- 19390547
TI  - Medical Oncology: Second-line XELOX or FOLFOX-4 for metastatic colorectal cancer.
AB  - In the movement towards individualized treatment regimens, Rothenberg et al.
      validate XELOX as another available systemic therapy for patients being treated
      with second-line treatment for metastatic colorectal cancer. This paper adds to a
      growing body of data in the first-line and second-line setting that confirms the
      noninferiority of oral fluoropyrimidine-containing regimens.

PMID- 19390548
TI  - Chemotherapy: The role of ifosfamide and etoposide in Ewing sarcoma.
AB  - The EICESS-92 Trial compared the efficacy of cyclophosphamide and ifosfamide in
      patients with Ewing sarcoma. Subgroup analysis suggested that patients with
      large, localized tumors benefited from the addition of etoposide, whereas
      patients with metastases did not.

PMID- 19390549
TI  - Targeted Therapies: Bevacizumab and interferon-alpha in metastatic renal-cell
      carcinoma.
AB  - Rini and colleagues provide additional data on bevacizumab and interferon-alpha
      in clear-cell carcinoma of the kidney; a comparison of these results with the
      findings from contemporary trials suggests that bevacizumab and interferon-alpha
      is another clinically useful treatment option for patients with metastatic renal
      cell carcinoma.

PMID- 19390550
TI  - Hematology: Bortezomib in newly diagnosed multiple myeloma.
AB  - Preclinical studies have shown that new agents such as bortezomib not only
      demonstrate anti-multiple-myeloma activity as single agents but also enhance the
      efficacy of both chemotherapy and steroids. A randomized trial has established
      that bortezomib not only improves response rates but also prolongs the lives of
      patients with multiple myeloma who are not candidates for high-dose chemotherapy.

PMID- 19390551
TI  - Immunotherapy: Vaccine trials in melanoma -- time for reflection.
AB  - The disappointing results of the large, randomized, controlled trials showing no
      benefit of vaccines in patients with advanced and metastatic melanoma call for a
      reassessment of the development of therapeutic vaccines and the importance of
      better immune monitoring methodology, such as adoptive T-cell therapy with
      lymphodepletion.

PMID- 19390552
TI  - Next generation oncology drug development: opportunities and challenges.
AB  - The optimal development of novel molecularly targeted agents for the treatment of
      cancer requires a re-evaluation of the current drug development paradigm.
      Selection of patients, optimal biologic dose versus maximum tolerated dose,
      definition of response and clinical benefit and trial designs that address these
      considerations are the focus of debate in the field of early cancer therapeutics.
      We present a review of the opportunities and challenges facing drug development
      in oncology through the phases of clinical development starting with first-in
      human trials.

PMID- 19390553
TI  - Molecular therapy in head and neck oncology.
AB  - Therapeutic management of locally advanced, recurrent and metastatic head and
      neck squamous cell carcinoma (HNSCC) is often limited by a rather unfavorable
      efficacy and toxicity ratio. Since the 1990s, targeted molecular therapy has been
      extensively investigated both as a single modality and in combination with
      cytotoxic treatments, such as radiotherapy or chemotherapy. EGFR is commonly over
      expressed in HNSCC and is an attractive molecular target. The EGFR signaling
      pathway is involved in a variety of cellular responses including cell growth and
      proliferation, and monoclonal antibodies and small-molecule inhibitors have been
      developed to inhibit EGFR pathways. Agents that target angiogenesis have also
      been tested in combination with EGFR inhibitors. A number of phase I/II and phase
      III studies have demonstrated that patients with high-risk HNSCC or those
      receiving palliative treatment for recurrent or metastatic disease benefit from
      the addition of EGFR inhibitors to chemotherapy and radiotherapy. This Review
      discusses the rationale for using targeted therapies based on inhibition of EGFR
      and angiogenesis, and describes the most recent preclinical and clinical evidence
      of the important role for targeted therapies in the management of head and neck
      cancers.

PMID- 19390554
TI  - Mediastinal staging of NSCLC with endoscopic and endobronchial ultrasound.
AB  - Mediastinal staging of non-small-cell lung cancer (NSCLC) is of paramount
      importance. It distinguishes operable from inoperable disease, guides prognosis
      and allows accurate comparison of outcomes in clinical trials. Noninvasive
      imaging modalities for mediastinal staging include CT, PET and integrated PET-CT.
      Mediastinoscopy is considered the current gold standard; however, each of these
      techniques has limitations in sensitivity or specificity. These inadequacies mean
      that 10% of operations performed with curative intent in patients with NSCLC are
      futile, owing to inaccurate locoregional lymph-node staging. Endoscopic and
      endobronchial ultrasound-guided mediastinal lymph-node aspiration are important
      and promising innovative techniques with reported sensitivities and specificities
      higher than standard investigations. The role of these techniques in mediastinal
      lymph-node staging is evolving rapidly and early data suggest that they may
      diminish the need for invasive surgical staging of the mediastinum. Furthermore,
      these are outpatient procedures that do not require general anesthesia and may be
      combined safely in the same sitting, for optimal accuracy of mediastinal staging.
      We propose a new algorithm for the diagnosis and staging of NSCLC, based on the
      current evidence, which incorporates endoscopic and endobronchial ultrasound as a
      first investigation after CT in patients with intrathoracic disease.

PMID- 19390555
TI  - Reasons for response differences seen in the V15-32, INTEREST and IPASS trials.
AB  - The first phase III study to assess the effect of gefitinib and docetaxel on the
      survival of Japanese patients with non-small-cell lung cancer who received
      previous treatment with platinum doublets, the V15-32 trial, did not establish
      noninferiority of gefitinib over docetaxel in terms of the effect on overall
      survival, despite the results showing a twofold higher response rate to
      gefitinib. The overall survival favored docetaxel for the first 18 months and
      gefitinib thereafter. The INTEREST trial, which compared docetaxel and gefitinib,
      demonstrated noninferiority of gefitinib, and the survival curves were completely
      superimposed. In this trial, patients had been recruited from 24 countries from
      Europe, Asia, and North and South America. Results of the IPASS trial showed
      superior progression-free survival for gefitinib compared with the combination of
      carboplatin and paclitaxel as first-line treatment in Asian patients who were
      nonsmokers and had adenocarcinoma histology. In this Review, we discuss the
      reasons for the differences in the effects of molecular-targeted drugs and
      cytotoxic antineoplastic agents observed in these trials. We also highlight the
      magnitude of the antitumor activity of these two different categories of drugs,
      and discuss how this could affect future clinical trial design and analysis.

PMID- 19390556
TI  - Cerebral primitive neuroectodermal tumor in an adult with a heterozygous MSH2
      mutation.
AB  - BACKGROUND: A 37-year-old woman presented with a supratentorial cerebral mass,
      which was diagnosed histologically as a primitive neuroectodermal tumor. She had
      been treated for rectal adenocarcinoma 7 years previously. A family history
      revealed a young-onset colorectal carcinoma in the patient's father.
      INVESTIGATIONS: Immunohistochemical analysis for DNA mismatch repair proteins,
      germline mutation analysis of MSH2. DIAGNOSIS: Lynch syndrome with a heterozygous
      germline mutation in MSH2. MANAGEMENT: Debulking of the cerebral tumor,
      craniospinal axis radiotherapy, and genetic counseling of family.

PMID- 19390557
TI  - Different forms of cell death induced by putative BCL2 inhibitors.
AB  - Several inhibitors of BCL2 proteins have been identified that induce apoptosis in
      a variety of tumor cells, indicating their potential in cancer therapy. We
      investigated the specificity of six putative BCL2 inhibitors (obatoclax,
      gossypol, apogossypol, EM20-25, chelerythrine and ABT-737). Using cells deficient
      either for Bax/Bak or caspase-9, we found that only ABT-737 specifically targeted
      BCL2 proteins and induced apoptosis by activation of caspase-9, as only ABT-737
      induced apoptosis was completely inhibited in cells deficient for Bax/Bak or
      caspase-9. Our data show that only ABT-737 is a specific BCL2 inhibitor and all
      other compounds investigated were not specific for BCL2 proteins. Furthermore,
      investigations of the effects of these compounds in primary chronic lymphocytic
      leukemic cells showed that all compounds induced certain biochemical hallmarks of
      apoptosis, such as release of cytochrome c and caspase cleavage. However, they
      all caused strikingly different ultrastructural changes. ABT-737 induced all the
      characteristic ultrastructural changes of apoptosis together with early rupture
      of the outer mitochondrial membrane, whereas obatoclax, chlelerythrine and
      gossypol induced pronounced mitochondrial swelling with formation of phospholipid
      inclusions. Therefore, we conclude that biochemical measurements used earlier to
      define apoptosis like mitochondrial release of cytochrome c and caspase cleavage,
      are insufficient to distinguish between classic apoptosis and other forms of cell
      death.

PMID- 19390559
TI  - Spontaneous regression of a retinal fold a year after scleral buckling and
      intravitreal injection of gas.

PMID- 19390558
TI  - Cell death induced by dexamethasone in lymphoid leukemia is mediated through
      initiation of autophagy.
AB  - Glucocorticoids are fundamental drugs used in the treatment of lymphoid
      malignancies with apoptotic cell death as the hitherto proposed mechanism of
      action. Recent studies, however, showed that an alternative mode of cell death,
      autophagy, is involved in the response to anticancer drugs. The specific role of
      autophagy and its relationship to apoptosis remains, nevertheless, controversial:
      it can either lead to cell survival or can function in cell death. We show that
      dexamethasone induced autophagy upstream of apoptosis in acute lymphoblastic
      leukemia cells. Inhibition of autophagy by siRNA-mediated repression of Beclin 1
      expression inhibited apoptosis showing an important role of autophagy in
      dexamethasone-induced cell death. Dexamethasone treatment caused an upregulation
      of promyelocytic leukemia protein, PML, its complex formation with protein kinase
      B or Akt and a PML-dependent Akt dephosphorylation. Initiation of autophagy and
      the onset of apoptosis were both dependent on these events. PML knockout
      thymocytes were resistant to dexamethasone-induced death and upregulation of PML
      correlated with the ability of dexamethasone to kill primary leukemic cells. Our
      data reveal key mechanisms of dexamethasone-induced cell death that may inform
      the development of improved treatment protocols for lymphoid malignancies.

PMID- 19390560
TI  - Clinical outcomes and patient satisfaction after Visian Implantable Collamer Lens
      removal and phacoemulsification with intraocular lens implantation in eyes with
      induced cataract.
AB  - PURPOSE: To assess the clinical outcomes and patient satisfaction after
      simultaneous Implantable Collamer Lens (ICL) removal and phacoemulsification with
      intraocular lens (IOL) implantation in ICL-implanted eyes with developing
      cataracts. METHODS: We retrospectively reviewed the clinical charts of 10 eyes of
      eight patients who developed significant cataract after ICL implantation. Patient
      age was 47.2+/-5.9 (mean+/-SD) years (range, 37-57 years). We determined visual
      acuity (log MAR), manifest refraction, endothelial cell density, and subjective
      satisfaction with visual outcomes measured using a visual analogue scale, that
      ranged from 0 (very dissatisfied) to 10 (very satisfied), before and 3 months
      after cataract surgery. RESULTS: Log MAR best spectacle-corrected visual acuity
      was significantly improved from 0.19+/-0.30 preoperatively to -0.06+/-0.07
      postoperatively (P=0.007, Wilcoxon signed-rank test). Eight (80%) and nine (90%)
      of the 10 eyes were within 0.5 D (diopter) and 1.0 D of the targeted correction,
      respectively. The endothelial cell density was 2584.9+/-266.2 cells/mm(2)
      preoperatively, and 2340.1+/-269.7 cells/mm(2) postoperatively. The overall
      satisfaction with visual outcomes was scored 1.8+/-1.1 (range: 0-3)
      preoperatively, and 7.9+/-1.4 (range: 6-10) postoperatively. No vision
      threatening complications were seen throughout the follow-up period. CONCLUSIONS:
      Simultaneous ICL removal and phacoemulsification with IOL implantation was safe
      and effective with predictable refractive results, and thus yielded a high level
      of patient satisfaction with ICL-induced cataract treatment.

PMID- 19390561
TI  - Clinical coding of surgical procedures in the ophthalmology department.

PMID- 19390562
TI  - Correlation of visual recovery with macular height in macula-off retinal
      detachments.
AB  - OBJECTIVES: To determine the relationship between the preoperative macular height
      of a macular detachment and visual outcome of the post retinal reattachment.
      METHODS: Prospective case series of 26 patients who presented to the
      Wolverhampton Eye Infirmary with a primary rhegmatogenous macula-off retinal
      detachment. Macular detachment height was assessed by B-scan ultrasound (10 Mhz)
      in the seated and supine postures before surgery. Age, gender, duration of the
      detachment, type of surgery, preoperative (pre-op) and postoperative (post-op)
      visual acuities at 3 and 6 months and status of the fellow eye were noted.
      RESULTS: A total of 26 eyes of 26 patients (mean age: 61.4 years+/-15.56 SD) were
      recruited. The mean logMAR pre- and post-op visual acuities at 3 and 6 months
      were 1.5+/-1.1 SD (range: 0.2-3), 0.38+/-0.23 SD (range: 0-0.84), and at 6 months
      0.29+/-0.22 SD (range: 0-1.0). The median period of the macular detachment was
      4.5 days (95% CI: 2-8 days). There was no significant difference between the mean
      macular heights while seated 2.42 mm+/-1.2 or supine 2.39 mm+/-1.0 (t-test,
      P=0.9). Correlation showed that the pre-op macular height is a statistical
      predictor of post-op visual acuity in our group of patients with macula-off
      retinal detachments. CONCLUSIONS: The shallower the macular detachment the
      greater the likelihood of a good visual outcome.

PMID- 19390563
TI  - A comparison of induced astigmatism in 20- vs 25-gauge vitrectomy procedures.
AB  - INTRODUCTION: Surgically induced astigmatism is an unwanted variable that can
      lead to poorer visual and refractive outcomes in patients undergoing vitrectomy
      even when a technically precise procedure has been performed. This study assesses
      the difference in surgically induced astigmatism (SIA) between the traditional 20
      gauge vitrectomy and the newer 25-gauge sutureless technique by comparing pre-
      and post-procedure keratometry readings. METHOD: The study is a retrospective
      consecutive case series of vitrectomies performed by a single surgeon. There were
      a total of 47 patients, eight with bilateral procedures, 24 who underwent the 20
      gauge, and 31 who had the 25-gauge procedure. Patients were excluded for corneal
      altering pathology or scleral buckling procedures. Vector analysis of pre- and
      post-vitrectomy readings was performed using Alpin's method, facilitated by the
      ASSORT program version 4.1. RESULTS: Mean time at which post-operative
      keratometry readings were taken was 3.9 months (1-36). Mean astigmatism at
      presentation was 0.63 D and 0.92 D and at post-surgically follow-up 1.14 D and
      0.91 D (20 and 25 gauge, respectively). Mean SIA was 0.66 D (SD=0.8 D) for the 20
      gauge group and 0.27 D (SD=0.23 D) for the 25 gauge (P=0.037). The calculated
      figure of SIA variability representing the 95% CI for the maximum amount of SIA
      for each procedure was 2.26 D and 0.73 D for the 20- and 25-gauge procedure,
      respectively. CONCLUSIONS: The study shows that the 25-gauge technique involves a
      statistically significant reduction in the amount of SIA. This can ultimately
      lead to a better visual and refractive outcome for the patient.

PMID- 19390564
TI  - Correlation in foveal thickness measurements between spectral-domain and time
      domain optical coherence tomography in normal individuals.
AB  - PURPOSE: To compare a time-domain (Stratus) and a spectral-domain (Spectralis)
      optical coherence tomography (OCT) device in assessing foveal thickness in
      healthy subjects. METHODS: In this observational study 40 healthy subjects (40
      eyes) underwent Stratus OCT and Spectralis OCT measurements of foveal thickness
      using three consecutive horizontal and vertical B-scan. Paired samples t-test was
      used to compare means between Stratus and Spectralis OCT measurements.
      Coefficient of variation (CoV) was used to compare dispersion in datasets.
      Pearson's correlation coefficient was used to quantify linear relation between
      Spectralis and Stratus OCT measurements. To assess agreement between Spectralis
      and Stratus OCT foveal thickness measurements, the Bland and Altman plots were
      used. RESULTS: Sample age ranged from 19 to 49 years (mean 33.25, standard
      deviation (SD) +/-4.22). The Spectralis OCT foveal thickness measurements
      resulted significantly higher than those obtained with Stratus OCT (227.64+/
      11.74 vs 144.36+/-12.25 microm, and 227.63+/-11.43 vs 144.92+/-12.34 microm, for
      horizontal and vertical foveal thickness, respectively) (P<0.05). Coefficient of
      variations were 5.16 and 5.02% using Spectralis OCT, and 8.49 and 8.51% using
      Stratus OCT. Mean Spectralis/Stratus ratio was 1.58 for both horizontal and
      vertical measurements. A linear relation between the two technologies was found
      (r(horiz)=0.899 and r(vert)=0.869) (P<0.001). CONCLUSIONS: A good correlation
      between Stratus and Spectralis OCT foveal measurements was found, independently
      of retinal thickness. This preliminary study suggests the existence of a
      conversion factor between Stratus and Spectralis OCT when measuring healthy
      foveal thickness.

PMID- 19390565
TI  - Bilateral papillitis in ocular toxoplasmosis.

PMID- 19390566
TI  - Immunoregulatory functions of mTOR inhibition.
AB  - The potent immunosuppressive action of rapamycin is commonly ascribed to
      inhibition of growth factor-induced T cell proliferation. However, it is now
      evident that the serine/threonine protein kinase mammalian target of rapamycin
      (mTOR) has an important role in the modulation of both innate and adaptive immune
      responses. mTOR regulates diverse functions of professional antigen-presenting
      cells, such as dendritic cells (DCs), and has important roles in the activation
      of effector T cells and the function and proliferation of regulatory T cells. In
      this Review, we discuss our current understanding of the mTOR pathway and the
      consequences of mTOR inhibition, both in DCs and T cells, including new data on
      the regulation of forkhead box P3 expression.

PMID- 19390569
TI  - The anticoagulants market.

PMID- 19390567
TI  - Intravascular immunity: the host-pathogen encounter in blood vessels.
AB  - The immune system provides an essential defence against invading pathogens.
      However, bacteria have evolved numerous strategies to overcome this defence, many
      of which facilitate systemic dissemination of the pathogen. Nevertheless, the
      host has evolved many mechanisms to detect and protect against pathogens in the
      vasculature. Recent studies using new imaging approaches and new mouse models are
      revealing previously unappreciated functions of this intravascular aspect of the
      immune system. In this Review, we summarize recent work in this field,
      highlighting in vivo imaging studies that examine the behaviour of both the
      immune system and bacteria in the highly dynamic microvasculature.

PMID- 19390568
TI  - Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a
      therapeutic antitumor response.
AB  - Interleukin 23 (IL-23) is a member of the IL-12 family of heterodimeric
      cytokines, composed of p19 and p40 subunits, which exhibits immunostimulatory
      properties similar to IL-12. IL-23 has been shown to possess potent antitumor
      activities in several establishment models of cancer and a few therapeutic
      models, but the efficacy of local, adenoviral-mediated expression of IL-23 in
      established tumors has yet to be investigated. Here we have examined the
      antitumor activity of adenovirally delivered IL-23 in a day-7 MCA205 murine
      fibrosarcoma tumor model. Three intratumoral injections of adenovirus expressing
      IL-23 (Ad.IL-23) significantly increased animal survival and resulted in complete
      rejection of 40% of tumors, with subsequent generation of protective immunity and
      MCA205-specific cytotoxic T lymphocytes. In addition, we have shown that the
      antitumor activity of IL-23 is independent of IL-17, perforin and Fas ligand, but
      dependent on interferon-gamma, CD4(+) and CD8(+) T cells. These results
      demonstrate that direct intratumoral injection of adenovirus expressing IL-23
      results in enhanced survival, tumor eradication and generation of protective
      immunity by generation of a Th1-type immune response.

PMID- 19390570
TI  - DNA-based diet analysis for any predator.
AB  - BACKGROUND: Prey DNA from diet samples can be used as a dietary marker; yet
      current methods for prey detection require a priori diet knowledge and/or are
      designed ad hoc, limiting their scope. I present a general approach to detect
      diverse prey in the feces or gut contents of predators. METHODOLOGY/PRINCIPAL
      FINDINGS: In the example outlined, I take advantage of the restriction site for
      the endonuclease Pac I which is present in 16S mtDNA of most Odontoceti mammals,
      but absent from most other relevant non-mammalian chordates and invertebrates.
      Thus in DNA extracted from feces of these mammalian predators Pac I will cleave
      and exclude predator DNA from a small region targeted by novel universal primers,
      while most prey DNA remain intact allowing prey selective PCR. The method was
      optimized using scat samples from captive bottlenose dolphins (Tursiops
      truncatus) fed a diet of 6-10 prey species from three phlya. Up to five prey from
      two phyla were detected in a single scat and all but one minor prey item (2% of
      the overall diet) were detected across all samples. The same method was applied
      to scat samples from free-ranging bottlenose dolphins; up to seven prey taxa were
      detected in a single scat and 13 prey taxa from eight teleost families were
      identified in total. CONCLUSIONS/SIGNIFICANCE: Data and further examples are
      provided to facilitate rapid transfer of this approach to any predator. This
      methodology should prove useful to zoologists using DNA-based diet techniques in
      a wide variety of study systems.

PMID- 19390571
TI  - Cardiac expression of microsomal triglyceride transfer protein is increased in
      obesity and serves to attenuate cardiac triglyceride accumulation.
AB  - Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart
      disease. Traditionally, the size of the cardiac triglyceride pool is thought to
      reflect the balance between uptake and beta-oxidation of fatty acids. However,
      triglycerides can also be exported from cardiomyocytes via secretion of
      apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on
      expression of microsomal triglyceride transfer protein (MTP); the mouse expresses
      two isoforms of MTP, A and B. Since many aspects of the link between obesity
      induced cardiac disease and cardiac lipid metabolism remain unknown, we
      investigated how cardiac lipoprotein synthesis affects cardiac expression of
      triglyceride metabolism-controlling genes, insulin sensitivity, and function in
      obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology
      impaired upregulation of MTP expression in response to increased fatty acid
      availability during fasting and fat feeding. This resulted in cardiac
      triglyceride accumulation but unaffected cardiac insulin-stimulated glucose
      uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac
      triglycerides, induced cardiac expression of triglyceride metabolism-controlling
      genes and attenuated heart function. Abolishing cardiac triglyceride accumulation
      in fat-fed mice by overexpression of an apoB transgene in the heart prevented the
      induction of triglyceride metabolism-controlling genes and improved heart
      function. The results suggest that in obesity, the physiological increase of
      cardiac MTP expression serves to attenuate cardiac triglyceride accumulation
      albeit without major effects on cardiac insulin sensitivity. Nevertheless, the
      data suggest that genetically increased lipoprotein secretion prevents
      development of obesity-induced lipotoxic heart disease.

PMID- 19390572
TI  - Limits of calcium clearance by plasma membrane calcium ATPase in olfactory cilia.
AB  - BACKGROUND: In any fine sensory organelle, a small influx of Ca(2+) can quickly
      elevate cytoplasmic Ca(2+). Mechanisms must exist to clear the ciliary Ca(2+)
      before it reaches toxic levels. One such organelle has been well studied: the
      vertebrate olfactory cilium. Recent studies have suggested that clearance from
      the olfactory cilium is mediated in part by plasma membrane Ca(2+)-ATPase (PMCA).
      PRINCIPAL FINDINGS: In the present study, electrophysiological assays were
      devised to monitor cytoplasmic free Ca(2+) in single frog olfactory cilia. Ca(2+)
      was allowed to enter isolated cilia, either through the detached end or through
      membrane channels. Intraciliary Ca(2+) was monitored via the activity of ciliary
      Ca(2+)-gated Cl(-) channels, which are sensitive to free Ca(2+) from about 2 to
      10 microM. No significant effect of MgATP on intraciliary free Ca(2+) could be
      found. Carboxyeosin, which has been used to inhibit PMCA, was found to
      substantially increase a ciliary transduction current activated by cyclic AMP.
      This increase was ATP-independent. CONCLUSIONS: Alternative explanations are
      suggested for two previous experiments taken to support a role for PMCA in
      ciliary Ca(2+) clearance. It is concluded that PMCA in the cilium plays a very
      limited role in clearing the micromolar levels of intraciliary Ca(2+) produced
      during the odor response.

PMID- 19390573
TI  - Assembling the marine metagenome, one cell at a time.
AB  - The difficulty associated with the cultivation of most microorganisms and the
      complexity of natural microbial assemblages, such as marine plankton or human
      microbiome, hinder genome reconstruction of representative taxa using cultivation
      or metagenomic approaches. Here we used an alternative, single cell sequencing
      approach to obtain high-quality genome assemblies of two uncultured, numerically
      significant marine microorganisms. We employed fluorescence-activated cell
      sorting and multiple displacement amplification to obtain hundreds of micrograms
      of genomic DNA from individual, uncultured cells of two marine flavobacteria from
      the Gulf of Maine that were phylogenetically distant from existing cultured
      strains. Shotgun sequencing and genome finishing yielded 1.9 Mbp in 17 contigs
      and 1.5 Mbp in 21 contigs for the two flavobacteria, with estimated genome
      recoveries of about 91% and 78%, respectively. Only 0.24% of the assembling
      sequences were contaminants and were removed from further analysis using rigorous
      quality control. In contrast to all cultured strains of marine flavobacteria, the
      two single cell genomes were excellent Global Ocean Sampling (GOS) metagenome
      fragment recruiters, demonstrating their numerical significance in the ocean. The
      geographic distribution of GOS recruits along the Northwest Atlantic coast
      coincided with ocean surface currents. Metabolic reconstruction indicated diverse
      potential energy sources, including biopolymer degradation, proteorhodopsin
      photometabolism, and hydrogen oxidation. Compared to cultured relatives, the two
      uncultured flavobacteria have small genome sizes, few non-coding nucleotides, and
      few paralogous genes, suggesting adaptations to narrow ecological niches. These
      features may have contributed to the abundance of the two taxa in specific
      regions of the ocean, and may have hindered their cultivation. We demonstrate the
      power of single cell DNA sequencing to generate reference genomes of uncultured
      taxa from a complex microbial community of marine bacterioplankton. A combination
      of single cell genomics and metagenomics enabled us to analyze the genome
      content, metabolic adaptations, and biogeography of these taxa.

PMID- 19390575
TI  - Lung cancer susceptibility model based on age, family history and genetic
      variants.
AB  - BACKGROUND: Epidemiological and pedigree studies suggest that lung cancer results
      from the combined effects of age, smoking, impaired lung function and genetic
      factors. In a case control association study of healthy smokers and lung cancer
      cases, we identified genetic markers associated with either susceptibility or
      protection to lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: We screened 157
      candidate single nucleotide polymorphisms (SNP) in a discovery cohort of 439
      subjects (200 controls and 239 lung cancer cases) and identified 30 SNPs
      associated with either the healthy smokers (protective) or lung cancer
      (susceptibility) phenotype. After genotyping this 30 SNP panel in a validation
      cohort of 491 subjects (248 controls and 207 lung cancers) and, using the same
      protective and susceptibility genotypes from our discovery cohort, a 20 SNP panel
      was selected based on replication of SNP associations in the validation cohort.
      Following multivariate logistic regression analyses, including the selected SNPs
      from runs 1 and 2, we found age and family history of lung cancer to be
      significantly and independently associated with lung cancer. Numeric scores were
      assigned to both the SNP and demographic data, and combined to form a simple
      algorithm of risk. CONCLUSIONS/SIGNIFICANCE: Significant differences in the
      distribution of the lung cancer susceptibility score was found between normal
      controls and lung cancer cases, which remained after accounting for differences
      in lung function. Validation in other case-control and prospective cohorts are
      underway to further define the potential clinical utility of this model.

PMID- 19390574
TI  - Features of mammalian microRNA promoters emerge from polymerase II chromatin
      immunoprecipitation data.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein
      coding genes. miRNAs play a very important role in diverse biological processes
      and various diseases. Many algorithms are able to predict miRNA genes and their
      targets, but their transcription regulation is still under investigation. It is
      generally believed that intragenic miRNAs (located in introns or exons of protein
      coding genes) are co-transcribed with their host genes and most intergenic miRNAs
      transcribed from their own RNA polymerase II (Pol II) promoter. However, the
      length of the primary transcripts and promoter organization is currently unknown.
      METHODOLOGY: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using
      a custom array surrounding regions of known miRNA genes. To identify the true
      core transcription start sites of the miRNA genes we developed a new tool (CPPP).
      We showed that miRNA genes can be transcribed from promoters located several
      kilobases away and that their promoters share the same general features as those
      of protein coding genes. Finally, we found evidence that as many as 26% of the
      intragenic miRNAs may be transcribed from their own unique promoters. CONCLUSION:
      miRNA promoters have similar features to those of protein coding genes, but miRNA
      transcript organization is more complex.

PMID- 19390576
TI  - Polo-like kinase-1 controls Aurora A destruction by activating APC/C-Cdh1.
AB  - Polo-like kinase-1 (Plk1) is activated before mitosis by Aurora A and its
      cofactor Bora. In mitosis, Bora is degraded in a manner dependent on Plk1 kinase
      activity and the E3 ubiquitin ligase SCF-betaTrCP. Here, we show that Plk1 is
      also required for the timely destruction of its activator Aurora A in late
      anaphase. It has been shown that Aurora A destruction is controlled by the
      auxiliary subunit Cdh1 of the Anaphase-Promoting Complex/Cyclosome (APC/C).
      Remarkably, we found that Plk1-depletion prevented the efficient
      dephosphorylation of Cdh1 during mitotic exit. Plk1 mediated its effect on Cdh1,
      at least in part, through direct phosphorylation of the human phosphatase Cdc14A,
      controlling the phosphorylation state of Cdh1. We conclude that Plk1 facilitates
      efficient Aurora A degradation through APC/C-Cdh1 activation after mitosis, with
      a potential role for hCdc14A.

PMID- 19390577
TI  - Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with
      Munc18.
AB  - Consensus exists that lipids must play key functions in synaptic activity but
      precise mechanistic information is limited. Acid sphingomyelinase knockout mice
      (ASMko) are a suitable model to address the role of sphingolipids in synaptic
      regulation as they recapitulate a mental retardation syndrome, Niemann Pick
      disease type A (NPA), and their neurons have altered levels of sphingomyelin (SM)
      and its derivatives. Electrophysiological recordings showed that ASMko hippocampi
      have increased paired-pulse facilitation and post-tetanic potentiation.
      Consistently, electron microscopy revealed reduced number of docked vesicles.
      Biochemical analysis of ASMko synaptic membranes unveiled higher amounts of SM
      and sphingosine (Se) and enhanced interaction of the docking molecules Munc18 and
      syntaxin1. In vitro reconstitution assays demonstrated that Se changes syntaxin1
      conformation enhancing its interaction with Munc18. Moreover, Se reduces vesicle
      docking in primary neurons and increases paired-pulse facilitation when added to
      wt hippocampal slices. These data provide with a novel mechanism for synaptic
      vesicle control by sphingolipids and could explain cognitive deficits of NPA
      patients.

PMID- 19390578
TI  - When one hemisphere takes control: metacontrol in pigeons (Columba livia).
AB  - BACKGROUND: Vertebrate brains are composed of two hemispheres that receive input,
      compute, and interact to form a unified response. How the partially different
      processes of both hemispheres are integrated to create a single output is largely
      unknown. In some cases one hemisphere takes charge of the response selection--a
      process known as metacontrol. Thus far, this phenomenon has only been shown in a
      handful of studies with primates, mostly conducted in humans. Metacontrol,
      however, is even more relevant for animals like birds with laterally placed eyes
      and complete chiasmatic decussation since visual input to the hemispheres is
      largely different. METHODOLOGY/PRINCIPAL FINDINGS: Homing pigeons (Columba livia)
      were trained with a color discrimination task. Each hemisphere was trained with a
      different color pair and therefore had a different experience. Subsequently, the
      pigeons were binocularly examined with two additional stimuli that combined the
      positive color of one hemisphere with a negative color that had been shown to the
      other, omitting the availability of a coherent solution and confronting the
      pigeons with a conflicting situation. Some of the pigeons responded to both
      stimuli, indicating that none of the hemispheres dominated the overall
      preference. Some birds, however, responded primarily to one of the conflicting
      stimuli, showing that they based their choice on the left- or right-monocularly
      learned color pair, indicating hemispheric metacontrol. CONCLUSIONS/SIGNIFICANCE:
      We could demonstrate for the first time that metacontrol is a widespread
      phenomenon that also exists in birds, and thus in principle requires no corpus
      callosum. Our results are closely similar to those in humans: monocular
      performance was higher than binocular one and animals displayed different modes
      of hemispheric dominance. Thus, metacontrol is a dynamic and widely distributed
      process that possibly constitutes a requirement for all animals with a bipartite
      brain to confront the problem of choosing between two hemisphere-bound behavioral
      options.

PMID- 19390579
TI  - Repertoire of microRNAs in epithelial ovarian cancer as determined by next
      generation sequencing of small RNA cDNA libraries.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small regulatory RNAs that are implicated in
      cancer pathogenesis and have recently shown promise as blood-based biomarkers for
      cancer detection. Epithelial ovarian cancer is a deadly disease for which
      improved outcomes could be achieved by successful early detection and enhanced
      understanding of molecular pathogenesis that leads to improved therapies. A
      critical step toward these goals is to establish a comprehensive view of miRNAs
      expressed in epithelial ovarian cancer tissues as well as in normal ovarian
      surface epithelial cells. METHODOLOGY: We used massively parallel pyrosequencing
      (i.e., "454 sequencing") to discover and characterize novel and known miRNAs
      expressed in primary cultures of normal human ovarian surface epithelium (HOSE)
      and in tissue from three of the most common histotypes of ovarian cancer. Deep
      sequencing of small RNA cDNA libraries derived from normal HOSE and ovarian
      cancer samples yielded a total of 738,710 high-quality sequence reads, generating
      comprehensive digital profiles of miRNA expression. Expression profiles for 498
      previously annotated miRNAs were delineated and we discovered six novel miRNAs
      and 39 candidate miRNAs. A set of 124 miRNAs was differentially expressed in
      normal versus cancer samples and 38 miRNAs were differentially expressed across
      histologic subtypes of ovarian cancer. Taqman qRT-PCR performed on a subset of
      miRNAs confirmed results of the sequencing-based study. CONCLUSIONS: This report
      expands the body of miRNAs known to be expressed in epithelial ovarian cancer and
      provides a useful resource for future studies of the role of miRNAs in the
      pathogenesis and early detection of ovarian cancer.

PMID- 19390580
TI  - Characterizing complex polysera produced by antigen-specific immunization through
      the use of affinity-selected mimotopes.
AB  - BACKGROUND: Antigen-based (as opposed to whole organism) vaccines are actively
      being pursued for numerous indications. Even though different formulations may
      produce similar levels of total antigen-specific antibody, the composition of the
      antibody response can be quite distinct resulting in different levels of
      therapeutic activity. METHODOLOGY/PRINCIPAL FINDINGS: Using plasmid-based
      immunization against the proto-oncogene HER-2 as a model, we have demonstrated
      that affinity-selected epitope mimetics (mimotopes) can provide a defined
      signature of a polyclonal antibody response. Further, using novel computer
      algorithms that we have developed, these mimotopes can be used to predict epitope
      targets. CONCLUSIONS/SIGNIFICANCE: By combining our novel strategy with existing
      methods of epitope prediction based on physical properties of an individual
      protein, we believe that this method offers a robust method for characterizing
      the breadth of epitope-specificity within a specific polyserum. This strategy is
      useful as a tool for monitoring immunity following vaccination and can also be
      used to define relevant epitopes for the creation of novel vaccines.

PMID- 19390581
TI  - Clusters of basic amino acids contribute to RNA binding and nucleolar
      localization of ribosomal protein L22.
AB  - The ribosomal protein L22 is a component of the 60S eukaryotic ribosomal subunit.
      As an RNA-binding protein, it has been shown to interact with both cellular and
      viral RNAs including 28S rRNA and the Epstein-Barr virus encoded RNA, EBER-1. L22
      is localized to the cell nucleus where it accumulates in nucleoli. Although
      previous studies demonstrated that a specific amino acid sequence is required for
      nucleolar localization, the RNA-binding domain has not been identified. Here, we
      investigated the hypothesis that the nucleolar accumulation of L22 is linked to
      its ability to bind RNA. To address this hypothesis, mutated L22 proteins were
      generated to assess the contribution of specific amino acids to RNA binding and
      protein localization. Using RNA-protein binding assays, we demonstrate that basic
      amino acids 80-93 are required for high affinity binding of 28S rRNA and EBER-1
      by L22. Fluorescence localization studies using GFP-tagged mutated L22 proteins
      further reveal that basic amino acids 80-93 are critical for nucleolar
      accumulation and for incorporation into ribosomes. Our data support the growing
      consensus that the nucleolar accumulation of ribosomal proteins may not be
      mediated by a defined localization signal, but rather by specific interaction
      with established nucleolar components such as rRNA.

PMID- 19390582
TI  - Characterizing gene expressions based on their temporal observations.
AB  - Temporal gene expression data are of particular interest to researchers as they
      contain rich information in characterization of gene function and have been
      widely used in biomedical studies. However, extracting information and
      identifying efficient treatment effects without loss of temporal information are
      still in problem. In this paper, we propose a method of classifying temporal gene
      expression curves in which individual expression trajectory is modeled as
      longitudinal data with changeable variance and covariance structure. The method,
      mainly based on generalized mixed model, is illustrated by a dense temporal gene
      expression data in bacteria. We aimed at evaluating gene effects and treatments.
      The power and time points of measurements are also characterized via the
      longitudinal mixed model. The results indicated that the proposed methodology is
      promising for the analysis of temporal gene expression data, and that it could be
      generally applicable to other high-throughput temporal gene expression analyses.

PMID- 19390583
TI  - Integrative decomposition procedure and Kappa statistics for the distinguished
      single molecular network construction and analysis.
AB  - Our method concentrates on and constructs the distinguished single gene network.
      An integrated method was proposed based on linear programming and a decomposition
      procedure with integrated analysis of the significant function cluster using
      Kappa statistics and fuzzy heuristic clustering. We tested this method to
      identify ATF2 regulatory network module using data of 45 samples from the same
      GEO dataset. The results demonstrate the effectiveness of such integrated way in
      terms of developing novel prognostic markers and therapeutic targets.

PMID- 19390584
TI  - Modulation of CXC chemokine receptor expression and function in human neutrophils
      during aging in vitro suggests a role in their clearance from circulation.
AB  - In mice, differential regulation of CXC chemokine receptor expression in
      circulating polymorphonuclear neutrophils (PMNs) undergoing senescence results in
      homing to the bone marrow. However, the role of this compartment and of the
      chemokine receptor CXCR4 is still under discussion, and only scarce data exist
      about CXCR4 function in human PMN. In our study, we provide evidence that also in
      human neutrophils, expression (cell surface and mRNA), chemotactic and signaling
      functions of the homing-related chemokine receptor CXCR4 are upregulated during
      aging in vitro, independent of addition of stimulatory cytokines (TNF, IL-1, IL
      8, G-CSF). In contrast, interleukin-8 receptors are downmodulated (CXCR2) or
      remain unchanged (CXCR1), suggesting that human PMNs undergoing senescence
      acquire a phenotype that impairs inflammatory extravasation and favors homing to
      the bone marrow or other tissues involved in sequestration. Partially retained
      responsiveness to interleukin-8 may be important for neutrophil function when
      senescence occurs after extravasation in inflamed tissues.

PMID- 19390586
TI  - Enhanced protection against Ebola virus mediated by an improved adenovirus-based
      vaccine.
AB  - BACKGROUND: The Ebola virus is transmitted by direct contact with bodily fluids
      of infected individuals, eliciting death rates as high as 90% among infected
      humans. Currently, replication defective adenovirus-based Ebola vaccine is being
      studied in a phase I clinical trial. Another Ebola vaccine, based on an
      attenuated vesicular stomatitis virus has shown efficacy in post-exposure
      treatment of nonhuman primates to Ebola infection. In this report, we modified
      the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the
      wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP). The immune
      response elicited by this improved expression cassette vector (Ad-CAGoptZGP) and
      its ability to afford protection against lethal ZEBOV challenge in mice was
      compared to the standard Ad-CMVZGP vector. METHODOLOGY/PRINCIPAL FINDINGS: Ad
      CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates
      from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression
      cassette of this vector was improved through codon optimization, inclusion of a
      consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP).
      Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP.
      Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100
      fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded
      full protections in mice against lethal challenge at a dose 100 times lower than
      the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to
      mice when given 30 minutes post-challenge. CONCLUSIONS/SIGNIFICANCE: We describe
      an improved adenovirus-based Ebola vaccine capable of affording post-exposure
      protection against lethal challenge in mice. The molecular modifications of the
      new improved vaccine also translated in the induction of significantly enhanced
      immune responses and complete protection at a dose 100 times lower than with the
      previous generation adenovirus-based Ebola vaccine. Understanding and improving
      the molecular components of adenovirus-based vaccines can produce potent,
      optimized product, useful for vaccination and post-exposure therapy.

PMID- 19390585
TI  - Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA
      1) administered in adjuvant system AS01B or AS02A.
AB  - BACKGROUND: This Phase 1/2a study evaluated the safety, immunogenicity, and
      efficacy of an experimental malaria vaccine comprised of the recombinant
      Plasmodium falciparum protein apical membrane antigen-1 (AMA-1) representing the
      3D7 allele formulated with either the AS01B or AS02A Adjuvant Systems.
      METHODOLOGY/PRINCIPAL FINDINGS: After a preliminary safety evaluation of low dose
      AMA-1/AS01B (10 microg/0.5 mL) in 5 adults, 30 malaria-naive adults were randomly
      allocated to receive full dose (50 microg/0.5 mL) of AMA-1/AS01B (n = 15) or AMA
      1/AS02A (n = 15), followed by a malaria challenge. All vaccinations were
      administered intramuscularly on a 0-, 1-, 2-month schedule. All volunteers
      experienced transient injection site erythema, swelling and pain. Two weeks post
      third vaccination, anti-AMA-1 Geometric Mean Antibody Concentrations (GMCs) with
      95% Confidence Intervals (CIs) were high: low dose AMA-1/AS01B 196 microg/mL (103
      371 microg/mL), full dose AMA-1/AS01B 279 microg/mL (210-369 microg/mL) and full
      dose AMA-1/AS02A 216 microg/mL (169-276 microg/mL) with no significant difference
      among the 3 groups. The three vaccine formulations elicited equivalent functional
      antibody responses, as measured by growth inhibition assay (GIA), against
      homologous but not against heterologous (FVO) parasites as well as demonstrable
      interferon-gamma (IFN-gamma) responses. To assess efficacy, volunteers were
      challenged with P. falciparum-infected mosquitoes, and all became parasitemic,
      with no significant difference in the prepatent period by either light microscopy
      or quantitative polymerase chain reaction (qPCR). However, a small but
      significant reduction of parasitemia in the AMA-1/AS02A group was seen with a
      statistical model employing qPCR measurements. SIGNIFICANCE: All three vaccine
      formulations were found to be safe and highly immunogenic. These immune responses
      did not translate into significant vaccine efficacy in malaria-naive adults
      employing a primary sporozoite challenge model, but encouragingly, estimation of
      parasite growth rates from qPCR data may suggest a partial biological effect of
      the vaccine. Further evaluation of the immunogenicity and efficacy of the AMA
      1/AS02A formulation is ongoing in a malaria-experienced pediatric population in
      Mali. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00385047.

PMID- 19390587
TI  - Integron gene cassettes and degradation of compounds associated with industrial
      waste: the case of the Sydney tar ponds.
AB  - Integrons are genetic platforms that accelerate lateral gene transfer (LGT) among
      bacteria. They were first detected on plasmids bearing single and multiple drug
      resistance determinants in human pathogens, and it is abundantly clear that
      integrons have played a major role in the evolution of this public health menace.
      Similar genetic elements can be found in nonpathogenic environmental bacteria and
      in metagenomic environmental DNA samples, and it is reasonable to suppose that
      integrons have facilitated microbial adaptation through LGT in niches outside
      infectious disease wards. Here we show that a heavily impacted estuary, exposed
      for almost a century to products of coal and steel industries, has developed a
      rich and unique cassette metagenome, containing genes likely to aid in the
      catabolism of compounds associated with industrial waste found there. In
      addition, we report that the most abundant cassette recovered in this study is
      one that encodes a putative LysR protein. This autoregulatory transcriptional
      regulator is known to activate transcription of linked target genes or unlinked
      regulons encoding diverse functions including chlorocatechol and dichlorophenol
      catabolism. Finally, only class 1 integrase genes were amplified in this study
      despite using different primer sets, and it may be that the cassettes present in
      the Tar Ponds will prove to be associated with class 1 integrase genes.
      Nevertheless, our cassette library provides a snapshot of a complex evolutionary
      process involving integron-meditated LGT likely to be important in natural
      bioremediation.

PMID- 19390588
TI  - Fatty fish intake decreases lipids related to inflammation and insulin signaling-
      a lipidomics approach.
AB  - BACKGROUND: The evidence of the multiple beneficial health effects of fish
      consumption is strong, but physiological mechanisms behind these effects are not
      completely known. Little information is available on the effects of consumption
      of different type of fish. The aim of this study was to investigate how fatty
      fish or lean fish in a diet affect serum lipidomic profiles in subjects with
      coronary heart disease. METHODOLOGY AND PRINCIPAL FINDINGS: A pilot study was
      designed which included altogether 33 subjects with myocardial infarction or
      unstable ischemic attack in an 8-week parallel controlled intervention. The
      subjects were randomized to either fatty fish (n = 11), lean fish (n = 12) or
      control (n = 10) groups. Subjects in the fish groups had 4 fish meals per week
      and subjects in the control group consumed lean beef, pork and chicken. A fish
      meal was allowed once a week maximum. Lipidomics analyses were performed using
      ultra performance liquid chromatography coupled to electrospray ionization mass
      spectrometry and gas chromatography. Multiple bioactive lipid species, including
      ceramides, lysophosphatidylcholines and diacylglycerols, decreased significantly
      in the fatty fish group, whereas in the lean fish group cholesterol esters and
      specific long-chain triacylglycerols increased significantly (False Discovery
      Rate q-value <0.05). CONCLUSIONS/SIGNIFICANCE: The 8-week consumption of fatty
      fish decreased lipids which are potential mediators of lipid-induced insulin
      resistance and inflammation, and may be related to the protective effects of
      fatty fish on the progression of atherosclerotic vascular diseases or insulin
      resistance. TRIAL REGISTRATION: ClinicalTrials.gov NCT00720655.

PMID- 19390589
TI  - Biological process linkage networks.
AB  - BACKGROUND: The traditional approach to studying complex biological networks is
      based on the identification of interactions between internal components of
      signaling or metabolic pathways. By comparison, little is known about
      interactions between higher order biological systems, such as biological pathways
      and processes. We propose a methodology for gleaning patterns of interactions
      between biological processes by analyzing protein-protein interactions,
      transcriptional co-expression and genetic interactions. At the heart of the
      methodology are the concept of Linked Processes and the resultant network of
      biological processes, the Process Linkage Network (PLN). RESULTS: We construct,
      catalogue, and analyze different types of PLNs derived from different data
      sources and different species. When applied to the Gene Ontology, many of the
      resulting links connect processes that are distant from each other in the
      hierarchy, even though the connection makes eminent sense biologically. Some
      others, however, carry an element of surprise and may reflect mechanisms that are
      unique to the organism under investigation. In this aspect our method complements
      the link structure between processes inherent in the Gene Ontology, which by its
      very nature is species-independent. As a practical application of the linkage of
      processes we demonstrate that it can be effectively used in protein function
      prediction, having the power to increase both the coverage and the accuracy of
      predictions, when carefully integrated into prediction methods. CONCLUSIONS: Our
      approach constitutes a promising new direction towards understanding the higher
      levels of organization of the cell as a system which should help current efforts
      to re-engineer ontologies and improve our ability to predict which proteins are
      involved in specific biological processes.

PMID- 19390590
TI  - Short-term striatal gene expression responses to brain-derived neurotrophic
      factor are dependent on MEK and ERK activation.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is believed to be an
      important regulator of striatal neuron survival, differentiation, and plasticity.
      Moreover, reduction of BDNF delivery to the striatum has been implicated in the
      pathophysiology of Huntington's disease. Nevertheless, many essential aspects of
      BDNF responses in striatal neurons remain to be elucidated. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we assessed the relative contributions of multipartite
      intracellular signaling pathways to the short-term induction of striatal gene
      expression by BDNF. To identify genes regulated by BDNF in these GABAergic cells,
      we first used DNA microarrays to quantify their transcriptomic responses
      following 3 h of BDNF exposure. The signal transduction pathways underlying gene
      induction were subsequently dissected using pharmacological agents and
      quantitative real-time PCR. Gene expression responses to BDNF were abolished by
      inhibitors of TrkB (K252a) and calcium (chelator BAPTA-AM and transient receptor
      potential cation channel [TRPC] antagonist SKF-96365). Interestingly, inhibitors
      of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) and extracellular
      signal-regulated kinase ERK also blocked the BDNF-mediated induction of all
      tested BDNF-responsive genes. In contrast, inhibitors of nitric oxide synthase
      (NOS), phosphotidylinositol-3-kinase (PI3K), and CAMK exhibited less prevalent,
      gene-specific effects on BDNF-induced RNA expression. At the nuclear level, the
      activation of both Elk-1 and CREB showed MEK dependence. Importantly, MEK
      dependent activation of transcription was shown to be required for BDNF-induced
      striatal neurite outgrowth, providing evidence for its contribution to striatal
      neuron plasticity. CONCLUSIONS: These results show that the MEK/ERK pathway is a
      major mediator of neuronal plasticity and other important BDNF-dependent striatal
      functions that are fulfilled through the positive regulation of gene expression.

PMID- 19390591
TI  - Screening for coping style increases the power of gene expression studies.
AB  - BACKGROUND: Individuals of many vertebrate species show different stress coping
      styles and these have a striking influence on how gene expression shifts in
      response to a variety of challenges. PRINCIPAL FINDINGS: This is clearly
      illustrated by a study in which common carp displaying behavioural predictors of
      different coping styles (characterised by a proactive, adrenaline-based or a
      reactive, cortisol-based response) were subjected to inflammatory challenge and
      specific gene transcripts measured in individual brains. Proactive and reactive
      fish differed in baseline gene expression and also showed diametrically opposite
      responses to the challenge for 80% of the genes investigated. SIGNIFICANCE:
      Incorporating coping style as an explanatory variable can account for some the
      unexplained variation that is common in gene expression studies, can uncover
      important effects that would otherwise have passed unnoticed and greatly enhances
      the interpretive value of gene expression data.

PMID- 19390593
TI  - Climate change and infectious disease.

PMID- 19390592
TI  - Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug
      resistance by inhibition of their transport function.
AB  - BACKGROUND: ABCC1 and ABCG2 are ubiquitous ATP-binding cassette transmembrane
      proteins that play an important role in multidrug resistance (MDR). In this
      study, we evaluated the possible interaction of vandetanib, an orally
      administered drug inhibiting multiple receptor tyrosine kinases, with ABCC1 and
      ABCG2 in vitro. METHODOLOGY AND PRINCIPAL FINDINGS: MDR cancer cells
      overexpressing ABCC1 or ABCG2 and their sensitive parental cell lines were used.
      MTT assay showed that vandetanib had moderate and almost equal-potent anti
      proliferative activity in both sensitive parental and MDR cancer cells.
      Concomitant treatment of MDR cells with vandetanib and specific inhibitors of
      ABCC1 or ABCG2 did not alter their sensitivity to the former drug. On the other
      hand, clinically attainable but non-toxic doses of vandetanib were found to
      significantly enhance the sensitivity of MDR cancer cells to ABCC1 or ABCG2
      substrate antitumor drugs. Flow cytometric analysis showed that vandetanib
      treatment significantly increase the intracellular accumulation of doxorubicin
      and rhodamine 123, substrates of ABCC1 and ABCG2 respectively, in a dose
      dependent manner (P<0.05). However, no significant effect was shown in sensitive
      parental cell lines. Reverse transcription-PCR and Western blot analysis showed
      that vandetanib did not change the expression of ABCC1 and ABCG2 at both mRNA and
      protein levels. Furthermore, total and phosphorylated forms of AKT and ERK1/2
      remained unchanged after vandetanib treatment in both sensitive and MDR cancer
      cells. CONCLUSIONS: Vandetanib is unlikely to be a substrate of ABCC1 or ABCG2.
      It overcomes ABCC1- and ABCG2-mediated drug resistance by inhibiting the
      transporter activity, independent of the blockade of AKT and ERK1/2 signal
      transduction pathways.

PMID- 19390594
TI  - Voltage gated calcium channels negatively regulate protective immunity to
      Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis modulates levels and activity of key intracellular
      second messengers to evade protective immune responses. Calcium release from
      voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In
      this study, we investigated the roles of VGCC in regulating protective immunity
      to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in
      dendritic cells (DCs) either using antibodies or by siRNA increased calcium
      influx in an inositol 1,4,5-phosphate and calcium release calcium activated
      channel dependent mechanism that resulted in increased expression of genes
      favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells
      that in turn mediated killing of M. tuberculosis inside macrophages. Likewise,
      inhibiting VGCC in infected macrophages and PBMCs induced calcium influx,
      upregulated the expression of pro-inflammatory genes and resulted in enhanced
      killing of intracellular M. tuberculosis. Importantly, compared to healthy
      controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC,
      which were significantly reduced following chemotherapy. Finally, blocking VGCC
      in vivo in M. tuberculosis infected mice using specific antibodies increased
      intracellular calcium and significantly reduced bacterial loads. These results
      indicate that L-type and R-type VGCC play a negative role in M. tuberculosis
      infection by regulating calcium mobilization in cells that determine protective
      immunity.

PMID- 19390595
TI  - The metal chelators, trientine and citrate, inhibit the development of cardiac
      pathology in the Zucker diabetic rat.
AB  - PURPOSE: The objective of this study was to determine the efficacy of dietary
      supplementation with the metal chelators, trientine or citric acid, in preventing
      the development of cardiomyopathy in the Zucker diabetic rat. HYPOTHESIS: We
      hypothesized that dietary chelators would attenuate metal-catalyzed oxidative
      stress and damage in tissues and protect against pathological changes in
      ventricular structure and function in type II diabetes. METHODS: Animals (10
      weeks old) included lean control (LC, fa/+), untreated Zucker diabetic fatty
      (ZDF, fa/fa), and ZDF rats treated with either trientine (triethylenetetramine)
      or citrate at 20 mg/d in drinking water, starting when rats were frankly
      diabetic. Cardiac functional assessment was determined using a Millar
      pressure/volume catheter placed in the left ventricle at 32 weeks of age.
      RESULTS: End diastolic volume for the ZDF animals increased by 36% indicating LV
      dilatation (P < .05) and was accompanied by a 30% increase in the end diastolic
      pressure (P <or= .05). Both trientine and citric acid prevented the increases in
      EDV and EDP (P < .05). Ejection fraction and myocardial relaxation were also
      significantly improved with chelator treatment. CONCLUSION: Dietary
      supplementation with trientine and citric acid significantly prevented structural
      and functional changes in the diabetic heart, supporting the merits of mild
      chelators for prevention of cardiovascular disease in diabetes.

PMID- 19390596
TI  - The spliceosomal phosphopeptide P140 controls the lupus disease by interacting
      with the HSC70 protein and via a mechanism mediated by gammadelta T cells.
AB  - The phosphopeptide P140 issued from the spliceosomal U1-70K snRNP protein is
      recognized by lupus CD4(+) T cells, transiently abolishes T cell reactivity to
      other spliceosomal peptides in P140-treated MRL/lpr mice, and ameliorates their
      clinical features. P140 modulates lupus patients' T cell response ex vivo and is
      currently included in phase IIb clinical trials. Its underlying mechanism of
      action remains elusive. Here we show that P140 peptide binds a unique cell
      surface receptor, the constitutively-expressed chaperone HSC70 protein, known as
      a presenting-protein. P140 induces apoptosis of activated MRL/lpr CD4(+) T cells.
      In P140-treated mice, it increases peripheral blood lymphocyte apoptosis and
      decreases B cell, activated T cell, and CD4(-)CD8(-)B220(+) T cell counts via a
      specific mechanism strictly depending on gammadelta T cells. Expression of
      inflammation-linked genes is rapidly regulated in CD4(+) T cells. This work led
      us to identify a powerful pathway taken by a newly-designed therapeutic peptide
      to immunomodulate lupus autoimmunity.

PMID- 19390598
TI  - Ten simple rules to combine teaching and research.

PMID- 19390597
TI  - A model of ischemia-induced neuroblast activation in the adult subventricular
      zone.
AB  - We have developed a rat brain organotypic culture model, in which tissue slices
      contain cortex-subventricular zone-striatum regions, to model neuroblast activity
      in response to in vitro ischemia. Neuroblast activation has been described in
      terms of two main parameters, proliferation and migration from the subventricular
      zone into the injured cortex. We observed distinct phases of neuroblast
      activation as is known to occur after in vivo ischemia. Thus, immediately after
      oxygen/glucose deprivation (6-24 hours), neuroblasts reduce their proliferative
      and migratory activity, whereas, at longer time points after the insult (2 to 5
      days), they start to proliferate and migrate into the damaged cortex. Antagonism
      of ionotropic receptors for extracellular ATP during and after the insult unmasks
      an early activation of neuroblasts in the subventricular zone, which responded
      with a rapid and intense migration of neuroblasts into the damaged cortex (within
      24 hours). The process is further enhanced by elevating the production of the
      chemoattractant SDf-1alpha and may also be boosted by blocking the activation of
      microglia. This organotypic model which we have developed is an excellent in
      vitro system to study neurogenesis after ischemia and other neurodegenerative
      diseases. Its application has revealed a SOS response to oxygen/glucose
      deprivation, which is inhibited by unfavorable conditions due to the ischemic
      environment. Finally, experimental quantifications have allowed us to elaborate a
      mathematical model to describe neuroblast activation and to develop a computer
      simulation which should have promising applications for the screening of drug
      candidates for novel therapies of ischemia-related pathologies.

PMID- 19390599
TI  - Webb Miller and Trey Ideker to receive top international bioinformatics awards
      for 2009 from the International Society for Computational Biology.

PMID- 19390600
TI  - Mechanism of genomic instability in cells infected with the high-risk human
      papillomaviruses.
AB  - In HPV-related cancers, the "high-risk" human papillomaviruses (HPVs) are
      frequently found integrated into the cellular genome. The integrated subgenomic
      HPV fragments express viral oncoproteins and carry an origin of DNA replication
      that is capable of initiating bidirectional DNA re-replication in the presence of
      HPV replication proteins E1 and E2, which ultimately leads to rearrangements
      within the locus of the integrated viral DNA. The current study indicates that
      the E1- and E2-dependent DNA replication from the integrated HPV origin follows
      the "onion skin"-type replication mode and generates a heterogeneous population
      of replication intermediates. These include linear, branched, open circular, and
      supercoiled plasmids, as identified by two-dimensional neutral-neutral gel
      electrophoresis. We used immunofluorescence analysis to show that the DNA
      repair/recombination centers are assembled at the sites of the integrated HPV
      replication. These centers recruit viral and cellular replication proteins, the
      MRE complex, Ku70/80, ATM, Chk2, and, to some extent, ATRIP and Chk1 (S317). In
      addition, the synthesis of histone gammaH2AX, which is a hallmark of DNA double
      strand breaks, is induced, and Chk2 is activated by phosphorylation in the HPV
      replicating cells. These changes suggest that the integrated HPV replication
      intermediates are processed by the activated cellular DNA repair/recombination
      machinery, which results in cross-chromosomal translocations as detected by
      metaphase FISH. We also confirmed that the replicating HPV episomes that
      expressed the physiological levels of viral replication proteins could induce
      genomic instability in the cells with integrated HPV. We conclude that the HPV
      replication origin within the host chromosome is one of the key factors that
      triggers the development of HPV-associated cancers. It could be used as a
      starting point for the "onion skin"-type of DNA replication whenever the HPV
      plasmid exists in the same cell, which endangers the host genomic integrity
      during the initial integration and after the de novo infection.

PMID- 19390601
TI  - Genetic evidence that the non-homologous end-joining repair pathway is involved
      in LINE retrotransposition.
AB  - Long interspersed elements (LINEs) are transposable elements that proliferate
      within eukaryotic genomes, having a large impact on eukaryotic genome evolution.
      LINEs mobilize via a process called retrotransposition. Although the role of the
      LINE-encoded protein(s) in retrotransposition has been extensively investigated,
      the participation of host-encoded factors in retrotransposition remains unclear.
      To address this issue, we examined retrotransposition frequencies of two
      structurally different LINEs--zebrafish ZfL2-2 and human L1--in knockout chicken
      DT40 cell lines deficient in genes involved in the non-homologous end-joining
      (NHEJ) repair of DNA and in human HeLa cells treated with a drug that inhibits
      NHEJ. Deficiencies of NHEJ proteins decreased retrotransposition frequencies of
      both LINEs in these cells, suggesting that NHEJ is involved in LINE
      retrotransposition. More precise characterization of ZfL2-2 insertions in DT40
      cells permitted us to consider the possibility of dual roles for NHEJ in LINE
      retrotransposition, namely to ensure efficient integration of LINEs and to
      restrict their full-length formation.

PMID- 19390602
TI  - The RNA polymerase dictates ORF1 requirement and timing of LINE and SINE
      retrotransposition.
AB  - Mobile elements comprise close to one half of the mass of the human genome. Only
      LINE-1 (L1), an autonomous non-Long Terminal Repeat (LTR) retrotransposon, and
      its non-autonomous partners-such as the retropseudogenes, SVA, and the SINE, Alu
      are currently active human retroelements. Experimental evidence shows that Alu
      retrotransposition depends on L1 ORF2 protein, which has led to the presumption
      that LINEs and SINEs share the same basic insertional mechanism. Our data
      demonstrate clear differences in the time required to generate insertions between
      marked Alu and L1 elements. In our tissue culture system, the process of L1
      insertion requires close to 48 hours. In contrast to the RNA pol II-driven L1, we
      find that pol III transcribed elements (Alu, the rodent SINE B2, and the 7SL, U6
      and hY sequences) can generate inserts within 24 hours or less. Our analyses
      demonstrate that the observed retrotransposition timing does not dictate
      insertion rate and is independent of the type of reporter cassette utilized. The
      additional time requirement by L1 cannot be directly attributed to differences in
      transcription, transcript length, splicing processes, ORF2 protein production, or
      the ability of functional ORF2p to reach the nucleus. However, the insertion rate
      of a marked Alu transcript drastically drops when driven by an RNA pol II
      promoter (CMV) and the retrotransposition timing parallels that of L1.
      Furthermore, the "pol II Alu transcript" behaves like the processed pseudogenes
      in our retrotransposition assay, requiring supplementation with L1 ORF1p in
      addition to ORF2p. We postulate that the observed differences in
      retrotransposition kinetics of these elements are dictated by the type of RNA
      polymerase generating the transcript. We present a model that highlights the
      critical differences of LINE and SINE transcripts that likely define their
      retrotransposition timing.

PMID- 19390603
TI  - Divisive gain modulation with dynamic stimuli in integrate-and-fire neurons.
AB  - The modulation of the sensitivity, or gain, of neural responses to input is an
      important component of neural computation. It has been shown that divisive gain
      modulation of neural responses can result from a stochastic shunting from
      balanced (mixed excitation and inhibition) background activity. This gain control
      scheme was developed and explored with static inputs, where the membrane and
      spike train statistics were stationary in time. However, input statistics, such
      as the firing rates of pre-synaptic neurons, are often dynamic, varying on
      timescales comparable to typical membrane time constants. Using a population
      density approach for integrate-and-fire neurons with dynamic and temporally rich
      inputs, we find that the same fluctuation-induced divisive gain modulation is
      operative for dynamic inputs driving nonequilibrium responses. Moreover, the
      degree of divisive scaling of the dynamic response is quantitatively the same as
      the steady-state responses--thus, gain modulation via balanced conductance
      fluctuations generalizes in a straight-forward way to a dynamic setting.

PMID- 19390604
TI  - Vesicular stomatitis virus enters cells through vesicles incompletely coated with
      clathrin that depend upon actin for internalization.
AB  - Many viruses that enter cells by clathrin-dependent endocytosis are significantly
      larger than the dimensions of a typical clathrin-coated vesicle. The mechanisms
      by which viruses co-opt the clathrin machinery for efficient internalization
      remain uncertain. Here we examined how clathrin-coated vesicles accommodate
      vesicular stomatitis virus (VSV) during its entry into cells. Using high
      resolution imaging of the internalization of single viral particles into cells
      expressing fluorescent clathrin and adaptor molecules, we show that VSV enters
      cells through partially clathrin-coated vesicles. We found that on average, virus
      containing vesicles contain more clathrin and clathrin adaptor molecules than
      conventional vesicles, but this increase is insufficient to permit full coating
      of the vesicle. We further show that virus-containing vesicles depend upon the
      actin machinery for their internalization. Specifically, we found that components
      of the actin machinery are recruited to virus-containing vesicles, and chemical
      inhibition of actin polymerization trapped viral particles in vesicles at the
      plasma membrane. By analysis of multiple independent virus internalization
      events, we show that VSV induces the nucleation of clathrin for its uptake,
      rather than depending upon random capture by formation of a clathrin-coated pit.
      This work provides new mechanistic insights into the process of virus
      internalization as well as uptake of unconventional cargo by the clathrin
      dependent endocytic machinery.

PMID- 19390605
TI  - Polymorphism data can reveal the origin of species abundance statistics.
AB  - What is the underlying mechanism behind the fat-tailed statistics observed for
      species abundance distributions? The two main hypotheses in the field are the
      adaptive (niche) theories, where species abundance reflects its fitness, and the
      neutral theory that assumes demographic stochasticity as the main factor
      determining community structure. Both explanations suggest quite similar species
      abundance distributions, but very different histories: niche scenarios assume
      that a species population in the past was similar to the observed one, while
      neutral scenarios are characterized by strongly fluctuating populations. Since
      the genetic variations within a population depend on its abundance in the past,
      we present here a way to discriminate between the theories using the genetic
      diversity of noncoding DNA. A statistical test, based on the Fu-Li method, has
      been developed and enables such a differentiation. We have analyzed the results
      gathered from individual-based simulation of both types of histories and obtained
      clear distinction between the Fu-Li statistics of the neutral scenario and that
      of the niche scenario. Our results suggest that data for 10-50 species, with
      approximately 30 sequenced individuals for each species, may allow one to
      distinguish between these two theories.

PMID- 19390606
TI  - Tumor-immune interaction, surgical treatment, and cancer recurrence in a
      mathematical model of melanoma.
AB  - Malignant melanoma is a cancer of the skin arising in the melanocytes. We present
      a mathematical model of melanoma invasion into healthy tissue with an immune
      response. We use this model as a framework with which to investigate primary
      tumor invasion and treatment by surgical excision. We observe that the presence
      of immune cells can destroy tumors, hold them to minimal expansion, or, through
      the production of angiogenic factors, induce tumorigenic expansion. We also find
      that the tumor-immune system dynamic is critically important in determining the
      likelihood and extent of tumor regrowth following resection. We find that small
      metastatic lesions distal to the primary tumor mass can be held to a minimal size
      via the immune interaction with the larger primary tumor. Numerical experiments
      further suggest that metastatic disease is optimally suppressed by immune
      activation when the primary tumor is moderately, rather than minimally,
      metastatic. Furthermore, satellite lesions can become aggressively tumorigenic
      upon removal of the primary tumor and its associated immune tissue. This can lead
      to recurrence where total cancer mass increases more quickly than in primary
      tumor invasion, representing a clinically more dangerous disease state. These
      results are in line with clinical case studies involving resection of a primary
      melanoma followed by recurrence in local metastases.

PMID- 19390607
TI  - Kinetics of mosquito-injected Plasmodium sporozoites in mice: fewer sporozoites
      are injected into sporozoite-immunized mice.
AB  - Malaria is initiated when the mosquito introduces sporozoites into the skin of a
      mammalian host. To successfully continue the infection, sporozoites must invade
      blood vessels in the dermis and be transported to the liver. A significant number
      of sporozoites, however, may enter lymphatic vessels in the skin or remain in the
      skin long after the mosquito bite. We have used fluorescence microscopy of
      Plasmodium berghei sporozoites expressing a fluorescent protein to evaluate the
      kinetics of sporozoite disappearance from the skin. Sporozoites injected into
      immunized mice were rapidly immobilized, did not appear to invade dermal blood
      vessels and became morphologically degraded within several hours. Strikingly,
      mosquitoes introduced significantly fewer sporozoites into immunized than into
      non-immunized mice, presumably by formation of an immune complex between soluble
      sporozoite antigens in the mosquito saliva and homologous host antibodies at the
      proboscis tip. These results indicate that protective antibodies directed against
      sporozoites may function both by reducing the numbers of sporozoites injected
      into immunized hosts and by inhibiting the movement of injected sporozoites into
      dermal blood vessels.

PMID- 19390608
TI  - Phasevarions mediate random switching of gene expression in pathogenic Neisseria.
AB  - Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes)
      that are subject to phase-variable expression (high-frequency reversible ON/OFF
      switching of gene expression). In Haemophilus influenzae, the random switching of
      the modA gene controls expression of a phase-variable regulon of genes (a
      "phasevarion"), via differential methylation of the genome in the modA ON and OFF
      states. Phase-variable mod genes are also present in Neisseria meningitidis and
      Neisseria gonorrhoeae, suggesting that phasevarions may occur in these important
      human pathogens. Phylogenetic studies on phase-variable mod genes associated with
      type III restriction modification (R-M) systems revealed that these organisms
      have two distinct mod genes--modA and modB. There are also distinct alleles of
      modA (abundant: modA11, 12, 13; minor: modA4, 15, 18) and modB (modB1, 2). These
      alleles differ only in their DNA recognition domain. ModA11 was only found in N.
      meningitidis and modA13 only in N. gonorrhoeae. The recognition site for the
      modA13 methyltransferase in N. gonorrhoeae strain FA1090 was identified as 5'
      AGAAA-3'. Mutant strains lacking the modA11, 12 or 13 genes were made in N.
      meningitidis and N. gonorrhoeae and their phenotype analyzed in comparison to a
      corresponding mod ON wild-type strain. Microarray analysis revealed that in all
      three modA alleles multiple genes were either upregulated or downregulated, some
      of which were virulence-associated. For example, in N. meningitidis MC58
      (modA11), differentially expressed genes included those encoding the candidate
      vaccine antigens lactoferrin binding proteins A and B. Functional studies using
      N. gonorrhoeae FA1090 and the clinical isolate O1G1370 confirmed that modA13 ON
      and OFF strains have distinct phenotypes in antimicrobial resistance, in a
      primary human cervical epithelial cell model of infection, and in biofilm
      formation. This study, in conjunction with our previous work in H. influenzae,
      indicates that phasevarions may be a common strategy used by host-adapted
      bacterial pathogens to randomly switch between "differentiated" cell types.

PMID- 19390610
TI  - Control of metabolic homeostasis by stress signaling is mediated by the lipocalin
      NLaz.
AB  - Metabolic homeostasis in metazoans is regulated by endocrine control of
      insulin/IGF signaling (IIS) activity. Stress and inflammatory signaling pathways-
      such as Jun-N-terminal Kinase (JNK) signaling--repress IIS, curtailing anabolic
      processes to promote stress tolerance and extend lifespan. While this interaction
      constitutes an adaptive response that allows managing energy resources under
      stress conditions, excessive JNK activity in adipose tissue of vertebrates has
      been found to cause insulin resistance, promoting type II diabetes. Thus, the
      interaction between JNK and IIS has to be tightly regulated to ensure proper
      metabolic adaptation to environmental challenges. Here, we identify a new
      regulatory mechanism by which JNK influences metabolism systemically. We show
      that JNK signaling is required for metabolic homeostasis in flies and that this
      function is mediated by the Drosophila Lipocalin family member Neural Lazarillo
      (NLaz), a homologue of vertebrate Apolipoprotein D (ApoD) and Retinol Binding
      Protein 4 (RBP4). Lipocalins are emerging as central regulators of peripheral
      insulin sensitivity and have been implicated in metabolic diseases. NLaz is
      transcriptionally regulated by JNK signaling and is required for JNK-mediated
      stress and starvation tolerance. Loss of NLaz function reduces stress resistance
      and lifespan, while its over-expression represses growth, promotes stress
      tolerance and extends lifespan--phenotypes that are consistent with reduced IIS
      activity. Accordingly, we find that NLaz represses IIS activity in larvae and
      adult flies. Our results show that JNK-NLaz signaling antagonizes IIS and is
      critical for metabolic adaptation of the organism to environmental challenges.
      The JNK pathway and Lipocalins are structurally and functionally conserved,
      suggesting that similar interactions represent an evolutionarily conserved system
      for the control of metabolic homeostasis.

PMID- 19390609
TI  - The genetic signatures of noncoding RNAs.
AB  - The majority of the genome in animals and plants is transcribed in a
      developmentally regulated manner to produce large numbers of non-protein-coding
      RNAs (ncRNAs), whose incidence increases with developmental complexity. There is
      growing evidence that these transcripts are functional, particularly in the
      regulation of epigenetic processes, leading to the suggestion that they compose a
      hitherto hidden layer of genomic programming in humans and other complex
      organisms. However, to date, very few have been identified in genetic screens.
      Here I show that this is explicable by an historic emphasis, both phenotypically
      and technically, on mutations in protein-coding sequences, and by presumptions
      about the nature of regulatory mutations. Most variations in regulatory sequences
      produce relatively subtle phenotypic changes, in contrast to mutations in protein
      coding sequences that frequently cause catastrophic component failure. Until
      recently, most mapping projects have focused on protein-coding sequences, and the
      limited number of identified regulatory mutations have been interpreted as
      affecting conventional cis-acting promoter and enhancer elements, although these
      regions are often themselves transcribed. Moreover, ncRNA-directed regulatory
      circuits underpin most, if not all, complex genetic phenomena in eukaryotes,
      including RNA interference-related processes such as transcriptional and post
      transcriptional gene silencing, position effect variegation, hybrid dysgenesis,
      chromosome dosage compensation, parental imprinting and allelic exclusion,
      paramutation, and possibly transvection and transinduction. The next frontier is
      the identification and functional characterization of the myriad sequence
      variations that influence quantitative traits, disease susceptibility, and other
      complex characteristics, which are being shown by genome-wide association studies
      to lie mostly in noncoding, presumably regulatory, regions. There is every
      possibility that many of these variations will alter the interactions between
      regulatory RNAs and their targets, a prospect that should be borne in mind in
      future functional analyses.

PMID- 19390611
TI  - Are viruses inhibited by APOBEC3 molecules from their host species?

PMID- 19390612
TI  - Naturally occurring lipid A mutants in neisseria meningitidis from patients with
      invasive meningococcal disease are associated with reduced coagulopathy.
AB  - Neisseria meningitidis is a major cause of bacterial meningitis and sepsis
      worldwide. Lipopolysaccharide (LPS), a major component of the Gram-negative
      bacterial outer membrane, is sensed by mammalian cells through Toll-like receptor
      4 (TLR4), resulting in activation of proinflammatory cytokine pathways. TLR4
      recognizes the lipid A moiety of the LPS molecule, and the chemical composition
      of the lipid A determines how well it is recognized by TLR4. N. meningitidis has
      been reported to produce lipid A with six acyl chains, the optimal number for
      TLR4 recognition. Indeed, meningococcal sepsis is generally seen as the
      prototypical endotoxin-mediated disease. In the present study, we screened
      meningococcal disease isolates from 464 patients for their ability to induce
      cytokine production in vitro. We found that around 9% of them were dramatically
      less potent than wild-type strains. Analysis of the lipid A of several of the low
      activity strains by mass spectrometry revealed they were penta-acylated,
      suggesting a mutation in the lpxL1 or lpxL2 genes required for addition of
      secondary acyl chains. Sequencing of these genes showed that all the low activity
      strains had mutations that inactivated the lpxL1 gene. In order to see whether
      lpxL1 mutants might give a different clinical picture, we investigated the
      clinical correlate of these mutations in a prospective nationwide observational
      cohort study of adults with meningococcal meningitis. Patients infected with an
      lpxL1 mutant presented significantly less frequently with rash and had higher
      thrombocyte counts, consistent with reduced cytokine induction and less
      activation of tissue-factor mediated coagulopathy. In conclusion, here we report
      for the first time that a surprisingly large fraction of meningococcal clinical
      isolates have LPS with underacylated lipid A due to mutations in the lpxL1 gene.
      The resulting low-activity LPS may have an important role in virulence by aiding
      the bacteria to evade the innate immune system. Our results provide the first
      example of a specific mutation in N. meningitidis that can be correlated with the
      clinical course of meningococcal disease.

PMID- 19390613
TI  - Mapping gene associations in human mitochondria using clinical disease
      phenotypes.
AB  - Nuclear genes encode most mitochondrial proteins, and their mutations cause
      diverse and debilitating clinical disorders. To date, 1,200 of these
      mitochondrial genes have been recorded, while no standardized catalog exists of
      the associated clinical phenotypes. Such a catalog would be useful to develop
      methods to analyze human phenotypic data, to determine genotype-phenotype
      relations among many genes and diseases, and to support the clinical diagnosis of
      mitochondrial disorders. Here we establish a clinical phenotype catalog of 174
      mitochondrial disease genes and study associations of diseases and genes.
      Phenotypic features such as clinical signs and symptoms were manually annotated
      from full-text medical articles and classified based on the hierarchical MeSH
      ontology. This classification of phenotypic features of each gene allowed for the
      comparison of diseases between different genes. In turn, we were then able to
      measure the phenotypic associations of disease genes for which we calculated a
      quantitative value that is based on their shared phenotypic features. The results
      showed that genes sharing more similar phenotypes have a stronger tendency for
      functional interactions, proving the usefulness of phenotype similarity values in
      disease gene network analysis. We then constructed a functional network of
      mitochondrial genes and discovered a higher connectivity for non-disease than for
      disease genes, and a tendency of disease genes to interact with each other.
      Utilizing these differences, we propose 168 candidate genes that resemble the
      characteristic interaction patterns of mitochondrial disease genes. Through their
      network associations, the candidates are further prioritized for the study of
      specific disorders such as optic neuropathies and Parkinson disease. Most
      mitochondrial disease phenotypes involve several clinical categories including
      neurologic, metabolic, and gastrointestinal disorders, which might indicate the
      effects of gene defects within the mitochondrial system. The accompanying
      knowledgebase (http://www.mitophenome.org/) supports the study of clinical
      diseases and associated genes.

PMID- 19390614
TI  - A structural model of the pore-forming region of the skeletal muscle ryanodine
      receptor (RyR1).
AB  - Ryanodine receptors (RyRs) are ion channels that regulate muscle contraction by
      releasing calcium ions from intracellular stores into the cytoplasm. Mutations in
      skeletal muscle RyR (RyR1) give rise to congenital diseases such as central core
      disease. The absence of high-resolution structures of RyR1 has limited our
      understanding of channel function and disease mechanisms at the molecular level.
      Here, we report a structural model of the pore-forming region of RyR1. Molecular
      dynamics simulations show high ion binding to putative pore residues D4899,
      E4900, D4938, and D4945, which are experimentally known to be critical for
      channel conductance and selectivity. We also observe preferential localization of
      Ca(2+) over K(+) in the selectivity filter of RyR1. Simulations of RyR1-D4899Q
      mutant show a loss of preference to Ca(2+) in the selectivity filter as seen
      experimentally. Electrophysiological experiments on a central core disease
      mutant, RyR1-G4898R, show constitutively open channels that conduct K(+) but not
      Ca(2+). Our simulations with G4898R likewise show a decrease in the preference of
      Ca(2+) over K(+) in the selectivity filter. Together, the computational and
      experimental results shed light on ion conductance and selectivity of RyR1 at an
      atomistic level.

PMID- 19390615
TI  - The role of the Frank-Starling law in the transduction of cellular work to whole
      organ pump function: a computational modeling analysis.
AB  - We have developed a multi-scale biophysical electromechanics model of the rat
      left ventricle at room temperature. This model has been applied to investigate
      the relative roles of cellular scale length dependent regulators of tension
      generation on the transduction of work from the cell to whole organ pump
      function. Specifically, the role of the length dependent Ca(2+) sensitivity of
      tension (Ca(50)), filament overlap tension dependence, velocity dependence of
      tension, and tension dependent binding of Ca(2+) to Troponin C on metrics of
      efficient transduction of work and stress and strain homogeneity were predicted
      by performing simulations in the absence of each of these feedback mechanisms.
      The length dependent Ca(50) and the filament overlap, which make up the Frank
      Starling Law, were found to be the two dominant regulators of the efficient
      transduction of work. Analyzing the fiber velocity field in the absence of the
      Frank-Starling mechanisms showed that the decreased efficiency in the
      transduction of work in the absence of filament overlap effects was caused by
      increased post systolic shortening, whereas the decreased efficiency in the
      absence of length dependent Ca(50) was caused by an inversion in the regional
      distribution of strain.

PMID- 19390616
TI  - The signal for signaling, found.

PMID- 19390617
TI  - A novel pathogenicity gene is required in the rice blast fungus to suppress the
      basal defenses of the host.
AB  - For successful colonization and further reproduction in host plants, pathogens
      need to overcome the innate defenses of the plant. We demonstrate that a novel
      pathogenicity gene, DES1, in Magnaporthe oryzae regulates counter-defenses
      against host basal resistance. The DES1 gene was identified by screening for
      pathogenicity-defective mutants in a T-DNA insertional mutant library.
      Bioinformatic analysis revealed that this gene encodes a serine-rich protein that
      has unknown biochemical properties, and its homologs are strictly conserved in
      filamentous Ascomycetes. Targeted gene deletion of DES1 had no apparent effect on
      developmental morphogenesis, including vegetative growth, conidial germination,
      appressorium formation, and appressorium-mediated penetration. Conidial size of
      the mutant became smaller than that of the wild type, but the mutant displayed no
      defects on cell wall integrity. The Deltades1 mutant was hypersensitive to
      exogenous oxidative stress and the activity and transcription level of
      extracellular enzymes including peroxidases and laccases were severely decreased
      in the mutant. In addition, ferrous ion leakage was observed in the Deltades1
      mutant. In the interaction with a susceptible rice cultivar, rice cells
      inoculated with the Deltades1 mutant exhibited strong defense responses
      accompanied by brown granules in primary infected cells, the accumulation of
      reactive oxygen species (ROS), the generation of autofluorescent materials, and
      PR gene induction in neighboring tissues. The Deltades1 mutant displayed a
      significant reduction in infectious hyphal extension, which caused a decrease in
      pathogenicity. Notably, the suppression of ROS generation by treatment with
      diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases, resulted in a
      significant reduction in the defense responses in plant tissues challenged with
      the Deltades1 mutant. Furthermore, the Deltades1 mutant recovered its normal
      infectious growth in DPI-treated plant tissues. These results suggest that DES1
      functions as a novel pathogenicity gene that regulates the activity of fungal
      proteins, compromising ROS-mediated plant defense.

PMID- 19390618
TI  - Parasite-dependent expansion of TNF receptor II-positive regulatory T cells with
      enhanced suppressive activity in adults with severe malaria.
AB  - Severe Plasmodium falciparum malaria is a major cause of global mortality, yet
      the immunological factors underlying progression to severe disease remain
      unclear. CD4(+)CD25(+) regulatory T cells (Treg cells) are associated with
      impaired T cell control of Plasmodium spp infection. We investigated the
      relationship between Treg cells, parasite biomass, and P. falciparum malaria
      disease severity in adults living in a malaria-endemic region of Indonesia.
      CD4(+)CD25(+)Foxp3(+)CD127(lo) Treg cells were significantly elevated in patients
      with uncomplicated (UM; n = 17) and severe malaria (SM; n = 16) relative to
      exposed asymptomatic controls (AC; n = 10). In patients with SM, Treg cell
      frequency correlated positively with parasitemia (r = 0.79, p = 0.0003) and total
      parasite biomass (r = 0.87, p<0.001), both major determinants for the development
      of severe and fatal malaria, and Treg cells were significantly increased in
      hyperparasitemia. There was a further significant correlation between Treg cell
      frequency and plasma concentrations of soluble tumor necrosis factor receptor II
      (TNFRII) in SM. A subset of TNFRII(+) Treg cells with high expression of Foxp3
      was increased in severe relative to uncomplicated malaria. In vitro, P.
      falciparum-infected red blood cells dose dependently induced TNFRII(+)Foxp3(hi)
      Treg cells in PBMC from malaria-unexposed donors which showed greater suppressive
      activity than TNFRII(-) Treg cells. The selective enrichment of the Treg cell
      compartment for a maximally suppressive TNFRII(+)Foxp3(hi) Treg subset in severe
      malaria provides a potential link between immune suppression, increased parasite
      biomass, and malaria disease severity. The findings caution against the induction
      of TNFRII(+)Foxp3(hi) Treg cells when developing effective malaria vaccines.

PMID- 19390619
TI  - Compartmentalized human immunodeficiency virus type 1 originates from long-lived
      cells in some subjects with HIV-1-associated dementia.
AB  - Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system
      (CNS) shortly after systemic infection and can result in the subsequent
      development of HIV-1-associated dementia (HAD) in a subset of infected
      individuals. Genetically compartmentalized virus in the CNS is associated with
      HAD, suggesting autonomous viral replication as a factor in the disease process.
      We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV
      1-associated neurological disease and in asymptomatic subjects who were
      initiating antiretroviral therapy. The heteroduplex tracking assay (HTA),
      targeting the variable regions of env, was used to determine which HIV-1 genetic
      variants in the cerebrospinal fluid (CSF) were compartmentalized and which
      variants were shared with the blood plasma. We then measured the viral decay
      kinetics of individual variants after the initiation of antiretroviral therapy.
      Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed
      rapidly after the initiation of antiretroviral therapy, with a mean half-life of
      1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants
      in four HAD subjects (t(1/2) mean = 2.27 days). However, slow viral decay was
      measured for CSF-compartmentalized variants from an additional four subjects with
      neurological disease (t(1/2) range = 9.85 days to no initial decay). The slow
      decay detected for CSF-compartmentalized variants was not associated with poor
      CNS drug penetration, drug resistant virus in the CSF, or the presence of X4
      virus genotypes. We found that the slow decay measured for CSF-compartmentalized
      variants in subjects with neurological disease was correlated with low peripheral
      CD4 cell count and reduced CSF pleocytosis. We propose a model in which
      infiltrating macrophages replace CD4(+) T cells as the primary source of
      productive viral replication in the CNS to maintain high viral loads in the CSF
      in a substantial subset of subjects with HAD.

PMID- 19390620
TI  - Accurate prediction of secreted substrates and identification of a conserved
      putative secretion signal for type III secretion systems.
AB  - The type III secretion system is an essential component for virulence in many
      Gram-negative bacteria. Though components of the secretion system apparatus are
      conserved, its substrates--effector proteins--are not. We have used a novel
      computational approach to confidently identify new secreted effectors by
      integrating protein sequence-based features, including evolutionary measures such
      as the pattern of homologs in a range of other organisms, G+C content, amino acid
      composition, and the N-terminal 30 residues of the protein sequence. The method
      was trained on known effectors from the plant pathogen Pseudomonas syringae and
      validated on a set of effectors from the animal pathogen Salmonella enterica
      serovar Typhimurium (S. Typhimurium) after eliminating effectors with detectable
      sequence similarity. We show that this approach can predict known secreted
      effectors with high specificity and sensitivity. Furthermore, by considering a
      large set of effectors from multiple organisms, we computationally identify a
      common putative secretion signal in the N-terminal 20 residues of secreted
      effectors. This signal can be used to discriminate 46 out of 68 total known
      effectors from both organisms, suggesting that it is a real, shared signal
      applicable to many type III secreted effectors. We use the method to make novel
      predictions of secreted effectors in S. Typhimurium, some of which have been
      experimentally validated. We also apply the method to predict secreted effectors
      in the genetically intractable human pathogen Chlamydia trachomatis, identifying
      the majority of known secreted proteins in addition to providing a number of
      novel predictions. This approach provides a new way to identify secreted
      effectors in a broad range of pathogenic bacteria for further experimental
      characterization and provides insight into the nature of the type III secretion
      signal.

PMID- 19390621
TI  - The mitochondrial A10398G polymorphism, interaction with alcohol consumption, and
      breast cancer risk.
AB  - Polymorphisms in the mitochondrial genome are hypothesized to be associated with
      risk of various diseases, including cancer. However, there has been conflicting
      evidence for associations between a common polymorphism in the mitochondrial
      genome (A10398G, G10398A in some prior reports) and breast cancer risk. Reactive
      oxygen species, a by-product of mitochondrial energy production, can lead to
      oxidative stress and DNA damage in both the mitochondria and their cells. Alcohol
      consumption, which may also lead to oxidative stress, is associated with breast
      cancer risk. Therefore, we hypothesized that polymorphisms in the mitochondrial
      genome interact with alcohol consumption to alter breast cancer risk. We
      genotyped the A10398G polymorphism in a case-control study nested within the
      Nurses' Health Study (NHS, 1,561 cases, 2,209 controls). We observed an
      interaction between alcohol consumption (yes/no) and A10398G on breast cancer
      risk (p-int = 0.03). The risk associated with alcohol consumption was limited to
      carriers of the 10398G allele (Odds Ratio 1.52, 95% Confidence Interval 1.10-2.08
      comparing drinkers to non-drinkers). However, we were unable to replicate these
      findings in the Women's Health Study (WHS, 678 cases, 669 controls), although the
      power to detect this interaction in the WHS was low (power = 0.57). Further
      examination of this interaction, such as sufficiently powered epidemiological
      studies of cancer risk or associations with biomarkers of oxidative stress, may
      provide further evidence for GxE interactions between the A10398G mitochondrial
      polymorphism and alcohol consumption on breast cancer risk.

PMID- 19390622
TI  - Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer.
AB  - This review will focus on recent advances in the application of antiepidermal
      growth factor receptor (anti-EGFR) for the treatment of breast cancer. The choice
      of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from
      evidence pinpointing its role in various anti-EGFR therapies. Therefore, an
      increase in our understanding of EGFR mechanism and signaling might reveal novel
      targets amenable to intervention in the clinic. This knowledge base might also
      improve existing medical treatment options and identify research gaps in the
      design of new therapeutic agents. While the approved use of drugs like the dual
      kinase inhibitor Lapatinib represents significant advances in the clinical
      management of breast cancer, confirmatory studies must be considered to foster
      the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical
      efficacy.

PMID- 19390624
TI  - Genetic variance in the adiponutrin gene family and childhood obesity.
AB  - AIM: The adiponutrin gene family consists of five genes (PNPLA1-5) coding for
      proteins with both lipolytic and lipogenic properties. PNPLA3 has previously been
      associated with adult obesity. Here we investigated the possible association
      between genetic variants in these genes and childhood and adolescent obesity.
      METHODS/RESULTS: Polymorphisms in the five genes of the adiponutrin gene family
      were selected and genotyped using the Sequenom platform in a childhood and
      adolescent obesity case-control study. Six variants in PNPLA1 showed association
      with obesity (rs9380559, rs12212459, rs1467912, rs4713951, rs10947600, and
      rs12199580, p<0.05 after adjustment for age and gender). Three variants in PNPLA3
      showed association with obesity before, but not after, adjustment for age and
      gender (rs139051, rs12483959, and rs2072907, p>0.05). When analyzing these SNPs
      in relation to phenotypes, two SNPs in the PNPLA3 gene showed association with
      insulin sensitivity (rs12483959: beta = -0.053, p = 0.016, and rs2072907: beta = 
      0.049, p = 0.024). No associations were seen for PNPLA2, PNPLA4, and PNPLA5.
      CONCLUSIONS: Genetic variation in the adiponutrin gene family does not seem to
      contribute strongly to obesity in children and adolescents. PNPLA1 exhibited a
      modest effect on obesity and PNPLA3 on insulin sensitivity. These data, however,
      require confirmation in other cohorts and ethnic groups.

PMID- 19390625
TI  - Flavodiiron proteins in oxygenic photosynthetic organisms: photoprotection of
      photosystem II by Flv2 and Flv4 in Synechocystis sp. PCC 6803.
AB  - BACKGROUND: Flavodiiron proteins (FDPs) comprise a group of modular enzymes that
      function in oxygen and nitric oxide detoxification in Bacteria and Archaea. The
      FDPs in cyanobacteria have an extra domain as compared to major prokaryotic
      enzymes. The physiological role of cyanobacteria FDPs is mostly unknown. Of the
      four putative flavodiiron proteins (Flv1-4) in the cyanobacterium Synechocystis
      sp. PCC 6803, a physiological function in Mehler reaction has been suggested for
      Flv1 and Flv3. PRINCIPAL FINDINGS: We demonstrate a novel and crucial function
      for Flv2 and Flv4 in photoprotection of photosystem II (PSII) in Synechocystis.
      It is shown that the expression of Flv2 and Flv4 is high under air level of CO(2)
      and negligible at elevated CO(2). Moreover, the rate of accumulation of flv2 and
      flv4 transcripts upon shift of cells from high to low CO(2) is strongly dependent
      on light intensity. Characterization of FDP inactivation mutants of Synechocystis
      revealed a specific decline in PSII centers and impaired translation of the D1
      protein in Delta flv2 and Delta flv4 when grown at air level CO(2) whereas at
      high CO(2) the Flvs were dispensable. Delta flv2 and Delta flv4 were also more
      susceptible to high light induced inhibition of PSII than WT or Delta flv1 and
      Delta flv3. SIGNIFICANCE: Analysis of published sequences revealed the presence
      of cyanobacteria-like FDPs also in some oxygenic photosynthetic eukaryotes like
      green algae, mosses and lycophytes. Our data provide evidence that Flv2 and Flv4
      have an important role in photoprotection of water-splitting PSII against
      oxidative stress when the cells are acclimated to air level CO(2). It is
      conceivable that the function of FDPs has changed during evolution from
      protection against oxygen in anaerobic microbes to protection against reactive
      oxygen species thus making the sustainable function of oxygen evolving PSII
      possible. Higher plants lack FDPs and distinctly different mechanisms have
      evolved for photoprotection of PSII.

PMID- 19390623
TI  - The renin-angiotensin system modulates inflammatory processes in atherosclerosis:
      evidence from basic research and clinical studies.
AB  - Recent evidence shows that the renin-angiotensin system is a crucial player in
      atherosclerotic processes. The regulation of arterial blood pressure was
      considered from its first description of the main mechanism involved.
      Vasoconstriction (mediated by angiotensin II) and salt and water retention
      (mainly due to aldosterone) were classically considered as pivotal
      proatherosclerotic activities. However, basic research and animal studies
      strongly support angiotensin II as a proinflammatory mediator, which directly
      induces atherosclerotic plaque development and heart remodeling. Furthermore,
      angiotensin II induces proatherosclerotic cytokine and chemokine secretion and
      increases endothelial dysfunction. Accordingly, the pharmacological inhibition of
      the renin-angiotensin system improves prognosis of patients with cardiovascular
      disease even in settings of normal baseline blood pressure. In the present
      review, we focused on angiotensin-convertingenzyme (ACE) inhibitors, angiotensin
      II receptor blockers (ARBs), and renin inhibitors to update the direct activities
      of the renin-angiotensin system in inflammatory processes governing
      atherosclerosis.

PMID- 19390627
TI  - Synthesis, characterization, and biological studies of organotin(IV) derivatives
      with o- or p-hydroxybenzoic acids.
AB  - Organotin(IV) complexes with o- or p-hydroxybenzoic acids (o-H(2)BZA or p
      H(2)BZA) of formulae [R(2)Sn(HL)(2)] (where H(2)L = o-H(2)BZA and R = Me- (1), n
      Bu- (2)); [R(3)Sn(HL)] (where H(2)L = o-H(2)BZA and R = n-Bu- (3), Ph- (4) or
      H(2)L = p-H(2)BZA and R = n-Bu- (5), Ph- (6)) were synthesized by reacting a
      methanolic solution of di- and triorganotin(IV) compounds with an aqueous
      solution of the ligand (o-H(2)BZA or p-H(2)BZA) containing equimolar amounts of
      potassium hydroxide. The complexes were characterized by elemental analysis, FT
      IR, Far-IR, TGA-DTA, FT-Raman, Mossbauer spectroscopy, (1)H, (119)Sn-NMR, UV/Vis
      spectroscopy, and Mass spectroscopy. The X-ray crystal structures of complexes 1
      and 2 have also been determined. Finally, the influence of these complexes 1-6
      upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by
      the enzyme lipoxygenase (LOX) was kinetically studied and the results showed that
      triorganotin(IV) complex 6 has the lowest IC(50) value. Also complexes 1-6 were
      studied for their in vitro cytotoxicity against sarcoma cancer cells (mesenchymal
      tissue) from the Wistar rat, and the results showed that the complexes have high
      activity against these cell lines with triphenyltin((IV) complex 4 to be the most
      active one.

PMID- 19390626
TI  - Metnase mediates resistance to topoisomerase II inhibitors in breast cancer
      cells.
AB  - DNA replication produces tangled, or catenated, chromatids, that must be
      decatenated prior to mitosis or catastrophic genomic damage will occur.
      Topoisomerase IIalpha (Topo IIalpha) is the primary decatenating enzyme. Cells
      monitor catenation status and activate decatenation checkpoints when decatenation
      is incomplete, which occurs when Topo IIalpha is inhibited by chemotherapy agents
      such as the anthracyclines and epididophyllotoxins. We recently demonstrated that
      the DNA repair component Metnase (also called SETMAR) enhances Topo IIalpha
      mediated decatenation, and hypothesized that Metnase could mediate resistance to
      Topo IIalpha inhibitors. Here we show that Metnase interacts with Topo IIalpha in
      breast cancer cells, and that reducing Metnase expression significantly increases
      metaphase decatenation checkpoint arrest. Repression of Metnase sensitizes breast
      cancer cells to Topo IIalpha inhibitors, and directly blocks the inhibitory
      effect of the anthracycline adriamycin on Topo IIalpha-mediated decatenation in
      vitro. Thus, Metnase may mediate resistance to Topo IIalpha inhibitors, and could
      be a biomarker for clinical sensitivity to anthracyclines. Metnase could also
      become an important target for combination chemotherapy with current Topo IIalpha
      inhibitors, specifically in anthracycline-resistant breast cancer.

PMID- 19390628
TI  - Temporal matching in endoscopic images for remote-controlled robotic surgery.
AB  - Temporal matching is applied in the frame of the formation of high-level entities
      in remote-controlled robotic surgery. The objective is to track tumor boundaries
      over time to improve the segmentation stage in each image of the sequence to
      facilitate the tracking and localization of the tumor. It makes use of an
      attributed string matching technique to find the correspondence between tumor
      boundaries over time. Relationships are then exploited to reconstitute the tumor
      boundaries and remove the inconsistencies coming from the detection errors. Input
      data are free form shapes of different length representing the tumor boundary,
      extracted at a previous stage.

PMID- 19390630
TI  - Phenotypic and functional characterization of human mammary stem/progenitor cells
      in long term culture.
AB  - BACKGROUND: Cancer stem cells exhibit close resemblance to normal stem cells in
      phenotype as well as function. Hence, studying normal stem cell behavior is
      important in understanding cancer pathogenesis. It has recently been shown that
      human breast stem cells can be enriched in suspension cultures as mammospheres.
      However, little is known about the behavior of these cells in long-term cultures.
      Since extensive self-renewal potential is the hallmark of stem cells, we
      undertook a detailed phenotypic and functional characterization of human
      mammospheres over long-term passages. METHODOLOGY: Single cell suspensions
      derived from human breast 'organoids' were seeded in ultra low attachment plates
      in serum free media. Resulting primary mammospheres after a week (termed T1
      mammospheres) were subjected to passaging every 7th day leading to the generation
      of T2, T3, and T4 mammospheres. PRINCIPAL FINDINGS: We show that primary
      mammospheres contain a distinct side-population (SP) that displays a
      CD24(low)/CD44(low) phenotype, but fails to generate mammospheres. Instead, the
      mammosphere-initiating potential rests within the CD44(high)/CD24(low) cells, in
      keeping with the phenotype of breast cancer-initiating cells. In serial sphere
      formation assays we find that even though primary (T1) mammospheres show
      telomerase activity and fourth passage T4 spheres contain label-retaining cells,
      they fail to initiate new mammospheres beyond T5. With increasing passages,
      mammospheres showed an increase in smaller sized spheres, reduction in
      proliferation potential and sphere forming efficiency, and increased
      differentiation towards the myoepithelial lineage. Significantly, staining for
      senescence-associated beta-galactosidase activity revealed a dramatic increase in
      the number of senescent cells with passage, which might in part explain the
      inability to continuously generate mammospheres in culture. CONCLUSIONS: Thus,
      the self-renewal potential of human breast stem cells is exhausted within five in
      vitro passages of mammospheres, suggesting the need for further improvisation in
      culture conditions for their long-term maintenance.

PMID- 19390631
TI  - A modeling-derived hypothesis on chronicity in respiratory diseases: desensitized
      pathogen recognition secondary to hyperactive IRAK/TRAF6 signaling.
AB  - Several chronic respiratory diseases exhibit hyperactive immune responses in the
      lung: abundant inflammatory mediators; infiltrating neutrophils, macrophages,
      lymphocytes and other immune cells; and increased level of proteases. Such
      diseases include cystic fibrosis (CF), chronic obstructive pulmonary disease
      (COPD) and severe/neutrophilic asthma. Paradoxically, patients with these
      diseases are also susceptible to detrimental bacterial infection and
      colonization. In this paper, we seek to explain how a positive feedback mechanism
      via IL-8 could lead to desensitization of epithelial cells to pathogen
      recognition thus perpetuating bacterial colonization and chronic disease states
      in the lung. Such insight was obtained from mathematical modeling of the
      IRAK/TRAF6 signaling module, and is consistent with existing clinical evidence.
      The potential implications for targeted treatment regimes for these persistent
      respiratory diseases are explored.

PMID- 19390629
TI  - PPARgamma2 polymorphism and human health.
AB  - The nuclear hormone receptor peroxisome proliferator activated receptor gamma
      (PPARgamma) is an important transcription factor regulating adipocyte
      differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous
      genetic mutations of PPARgamma have been identified and these mutations
      positively or negatively regulate insulin sensitivity. Among these, a relatively
      common polymorphism of PPARgamma, Pro12Ala of PPARgamma2, the isoform expressed
      only in adipose tissue has been shown to be associated with lower body mass
      index, enhanced insulin sensitivity, and resistance to the risk of type 2
      diabetes in human subjects carrying this mutation. Subsequent studies in
      different ethnic populations, however, have revealed conflicting results,
      suggesting a complex interaction between the PPARgamma2 Pro12Ala polymorphism and
      environmental factors such as the ratio of dietary unsaturated fatty acids to
      saturated fatty acids and/or between the PPARgamma2 Pro12Ala polymorphism and
      genetic factors such as polymorphic mutations in other genes. In addition, this
      polymorphic mutation in PPARgamma2 is associated with other aspects of human
      diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and
      aging. This review will highlight findings from recent studies.

PMID- 19390632
TI  - Familial resemblance of borderline personality disorder features: genetic or
      cultural transmission?
AB  - Borderline personality disorder is a severe personality disorder for which
      genetic research has been limited to family studies and classical twin studies.
      These studies indicate that genetic effects explain 35 to 45% of the variance in
      borderline personality disorder and borderline personality features. However,
      effects of non-additive (dominance) genetic factors, non-random mating and
      cultural transmission have generally not been explored. In the present study an
      extended twin-family design was applied to self-report data of twins (N = 5,017)
      and their siblings (N = 1,266), parents (N = 3,064) and spouses (N = 939) from
      4,015 families, to estimate the effects of additive and non-additive genetic and
      environmental factors, cultural transmission and non-random mating on individual
      differences in borderline personality features. Results showed that resemblance
      among biological relatives could completely be attributed to genetic effects.
      Variation in borderline personality features was explained by additive genetic
      (21%; 95% CI 17-26%) and dominant genetic (24%; 95% CI 17-31%) factors.
      Environmental influences (55%; 95% CI 51-60%) explained the remaining variance.
      Significant resemblance between spouses was observed, which was best explained by
      phenotypic assortative mating, but it had only a small effect on the genetic
      variance (1% of the total variance). There was no effect of cultural transmission
      from parents to offspring.

PMID- 19390634
TI  - Development and characterization of a high density SNP genotyping assay for
      cattle.
AB  - The success of genome-wide association (GWA) studies for the detection of
      sequence variation affecting complex traits in human has spurred interest in the
      use of large-scale high-density single nucleotide polymorphism (SNP) genotyping
      for the identification of quantitative trait loci (QTL) and for marker-assisted
      selection in model and agricultural species. A cost-effective and efficient
      approach for the development of a custom genotyping assay interrogating 54,001
      SNP loci to support GWA applications in cattle is described. A novel algorithm
      for achieving a compressed inter-marker interval distribution proved remarkably
      successful, with median interval of 37 kb and maximum predicted gap of <350 kb.
      The assay was tested on a panel of 576 animals from 21 cattle breeds and six
      outgroup species and revealed that from 39,765 to 46,492 SNP are polymorphic
      within individual breeds (average minor allele frequency (MAF) ranging from 0.24
      to 0.27). The assay also identified 79 putative copy number variants in cattle.
      Utility for GWA was demonstrated by localizing known variation for coat color and
      the presence/absence of horns to their correct genomic locations. The combination
      of SNP selection and the novel spacing algorithm allows an efficient approach for
      the development of high-density genotyping platforms in species having full or
      even moderate quality draft sequence. Aspects of the approach can be exploited in
      species which lack an available genome sequence. The BovineSNP50 assay described
      here is commercially available from Illumina and provides a robust platform for
      mapping disease genes and QTL in cattle.

PMID- 19390635
TI  - Identifying genes involved in cyclic processes by combining gene expression
      analysis and prior knowledge.
AB  - Based on time series gene expressions, cyclic genes can be recognized via
      spectral analysis and statistical periodicity detection tests. These cyclic genes
      are usually associated with cyclic biological processes, for example, cell cycle
      and circadian rhythm. The power of a scheme is practically measured by comparing
      the detected periodically expressed genes with experimentally verified genes
      participating in a cyclic process. However, in the above mentioned procedure the
      valuable prior knowledge only serves as an evaluation benchmark, and it is not
      fully exploited in the implementation of the algorithm. In addition, partial data
      sets are also disregarded due to their nonstationarity. This paper proposes a
      novel algorithm to identify cyclic-process-involved genes by integrating the
      prior knowledge with the gene expression analysis. The proposed algorithm is
      applied on data sets corresponding to Saccharomyces cerevisiae and Drosophila
      melanogaster, respectively. Biological evidences are found to validate the roles
      of the discovered genes in cell cycle and circadian rhythm. Dendrograms are
      presented to cluster the identified genes and to reveal expression patterns. It
      is corroborated that the proposed novel identification scheme provides a valuable
      technique for unveiling pathways related to cyclic processes.

PMID- 19390633
TI  - Saccharomyces cerevisiae: population divergence and resistance to oxidative
      stress in clinical, domesticated and wild isolates.
AB  - BACKGROUND: Saccharomyces cerevisiae has been associated with human life for
      millennia in the brewery and bakery. Recently it has been recognized as an
      emerging opportunistic pathogen. To study the evolutionary history of S.
      cerevisiae, the origin of clinical isolates and the importance of a virulence
      associated trait, population genetics and phenotypic assays have been applied to
      an ecologically diverse set of 103 strains isolated from clinics, breweries,
      vineyards, fruits, soil, commercial supplements and insect guts.
      METHODOLOGY/PRINCIPAL FINDINGS: DNA sequence data from five nuclear DNA loci were
      analyzed for population structure and haplotype distribution. Additionally, all
      strains were tested for survival of oxidative stress, a trait associated with
      microbial pathogenicity. DNA sequence analyses identified three genetic subgroups
      within the recombining S. cerevisiae strains that are associated with ecology,
      geography and virulence. Shared alleles suggest that the clinical isolates
      contain genetic contribution from the fruit isolates. Clinical and fruit isolates
      exhibit high levels of recombination, unlike the genetically homogenous soil
      isolates in which no recombination was detected. However, clinical and soil
      isolates were more resistant to oxidative stress than any other population,
      suggesting a correlation between survival in oxidative stress and yeast
      pathogenicity. CONCLUSIONS/SIGNIFICANCE: Population genetic analyses of S.
      cerevisiae delineated three distinct groups, comprising primarily the (i) human
      associated brewery and vineyard strains, (ii) clinical and fruit isolates (iii)
      and wild soil isolates from eastern U.S. The interactions between S. cerevisiae
      and humans potentiate yeast evolution and the development of genetically,
      ecologically and geographically divergent groups.

PMID- 19390636
TI  - Detection of biochemical pathways by probabilistic matching of phyletic vectors.
AB  - A phyletic vector, also known as a phyletic (or phylogenetic) pattern, is a
      binary representation of the presences and absences of orthologous genes in
      different genomes. Joint occurrence of two or more genes in many genomes results
      in closely similar binary vectors representing these genes, and this similarity
      between gene vectors may be used as a measure of functional association between
      genes. Better understanding of quantitative properties of gene co-occurrences is
      needed for systematic studies of gene function and evolution. We used the
      probabilistic iterative algorithm Psi-square to find groups of similar phyletic
      vectors. An extended Psi-square algorithm, in which pseudocounts are implemented,
      shows better sensitivity in identifying proteins with known functional links than
      our earlier hierarchical clustering approach. At the same time, the specificity
      of inferring functional associations between genes in prokaryotic genomes is
      strongly dependent on the pathway: phyletic vectors of the genes involved in
      energy metabolism and in de novo biosynthesis of the essential precursors tend to
      be lumped together, whereas cellular modules involved in secretion, motility,
      assembly of cell surfaces, biosynthesis of some coenzymes, and utilization of
      secondary carbon sources tend to be identified with much greater specificity. It
      appears that the network of gene coinheritance in prokaryotes contains a giant
      connected component that encompasses most biosynthetic subsystems, along with a
      series of more independent modules involved in cell interaction with the
      environment.

PMID- 19390637
TI  - Interfering with glycolysis causes Sir2-dependent hyper-recombination of
      Saccharomyces cerevisiae plasmids.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key metabolic regulator
      implicated in a variety of cellular processes. It functions as a glycolytic
      enzyme, a protein kinase, and a metabolic switch under oxidative stress. Its
      enzymatic inactivation causes a major shift in the primary carbohydrate flux.
      Furthermore, the protein is implicated in regulating transcription, ER-to-Golgi
      transport, and apoptosis. We found that Saccharomyces cerevisiae cells null for
      all GAPDH paralogues (Tdh1, Tdh2, and Tdh3) survived the counter-selection of a
      GAPDH-encoding plasmid when the NAD(+) metabolizing deacetylase Sir2 was
      overexpressed. This phenotype required a fully functional copy of SIR2 and
      resulted from hyper-recombination between S. cerevisiae plasmids. In the wild
      type background, GAPDH overexpression increased the plasmid recombination rate in
      a growth-condition dependent manner. We conclude that GAPDH influences yeast
      episome stability via Sir2 and propose a model for the interplay of Sir2, GAPDH,
      and the glycolytic flux.

PMID- 19390638
TI  - [Risk/protective factors, and their indices in research on adolescents problem
      behaviours.]
AB  - Description and explanation of adolescent problem behaviours are in a great part
      based on risk and protective factor analysis. Research on these factors provides
      many important data, but due to diversity and complexity of the variables
      analyzed, it is difficult to summarize their results. One way to deal with this
      problem is the utilization of risk and protective factor indices, which shows
      individuals' exposure to the sum of risk and protective factors.In this article
      eight studies explaining adolescent problem behaviours (mainly: substance use)
      based on risk/protective factor indices are discussed.The review indicates that
      study results are strongly influenced by authors' arbitraly decisions on
      risk/protective factors definitions, the initial list of studied variables, way
      of determining significant intensity of factors. The most undisputed is the
      result indicating that after controlling for other variables, both indices (risk
      and protective) are significant in cross-sectional explanations of problem
      behaviours. This finding strongly supports the argument for enhancement of
      protective factors in preventive interventions. However, the main disadvantage of
      studies based on indices is the "averaging" of importance of various factors,
      which makes it difficult to assess their specific impact on problem behaviours.

PMID- 19390639
TI  - Pausing purkinje cells in the cerebellum of the awake cat.
AB  - A recent controversy has emerged concerning the existence of long pauses,
      presumably reflecting bistability of membrane potential, in the cerebellar
      Purkinje cells (PC) of awake animals. It is generally agreed that in the
      anesthetized animals and in vitro, these cells switch between two stable membrane
      potential states: a depolarized state (the 'up-state') characterized by
      continuous firing of simple spikes (SS) and a hyperpolarized state (the 'down
      state') characterized by long pauses in the SS activity. To address the existence
      of long pauses in the neural activity of cerebellar PCs in the awake and behaving
      animal we used extracellular recordings in cats and find that approximately half
      of the recorded PCs exhibit such long pauses in the SS activity and transition
      between activity - periods with uninterrupted SS lasting an average of 1300 ms -
      and pauses up to several seconds. We called these cells pausing Purkinje cells
      (PPC) and they can easily be distinguished from continuous firing Purkinje cells.
      In most PPCs, state transitions in both directions were often associated (25% of
      state transitions) with complex spikes (CSs). This is consistent with
      intracellular findings of CS-driven state transitions. In sum, we present proof
      for the existence of long pauses in the PC SS activity that probably reflect
      underlying bistability, provide the first in-depth analysis of these pauses and
      show for the first time that transitions in and out of these pauses are related
      to CS firing in the awake and behaving animal.

PMID- 19390640
TI  - Two novel FBN1 mutations associated with ectopia lentis and marfanoid habitus in
      two Chinese families.
AB  - PURPOSE: To identify the molecular defects in the fibrillin-1 gene (FBN1) in two
      Chinese families with ectopia lentis (EL) and marfanoid habitus. METHODS: Five
      patients and eight non-carriers in the two families underwent complete physical,
      ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from
      leukocytes of venous blood of these individuals in the families as well as 100
      healthy normal controls. Polymerase chain reaction (PCR) amplification and direct
      sequencing of all 65 coding exons of FBN1 were analyzed. The functional
      consequences of the mutations were analyzed with various genomic resources.
      RESULTS: Two novel mutations of FBN1 were identified in our study. One is a
      splice defect in intron 17 (IVS 17-1G>T) adjacent to exon 18. The other is
      c.6182G>T in exon 50, which results in the substitution of cysteine by
      phenylalanine at codon 2,061 (p. C2061F). We provided strong evidences that the
      splice mutation would potentially lead to the skipping of exons after intron 17
      and that the missense mutation at codon 2,061 (p. C2061F) would destroy a
      disulfide bond. CONCLUSIONS: We detected two novel mutations in FBN1. Our results
      expand the mutation spectrum of FBN1 and help in the study of the molecular
      pathogenesis of Marfan syndrome and Marfan-related disorders.

PMID- 19390641
TI  - Molecular genetic characteristics of X-linked retinoschisis in Koreans.
AB  - PURPOSE: X-linked retinoschisis (XLRS) is a recessively inherited disorder that
      causes macular degeneration and resultant visual defect in young males. Many
      genetic studies had focused on the patients in Western countries. We
      characterized the mutational spectrum of the RS1 gene in Korean patients with
      XLRS, and aimed to provide genetic information of XLRS in an Asian population.
      METHODS: This study enrolled 17 unrelated probands and their mothers for
      molecular genetic evaluation. All exons and the flanking intronic regions of RS1
      were analyzed by direct sequencing. We performed gene dosage analysis by
      semiquantitative multiplex PCR to rule out the possibility of duplication in a
      patient without a sequence variation. We also tried RT-PCR analysis in a case
      with a putative splicing mutation. RESULTS: Genetic tests revealed 16 Korean
      patients (94.1%) had RS1 mutations. In one patient, neither sequence variation
      nor deletion or duplication in RS1 was detected. One case with de novo mutation
      was confirmed by familial analysis. Identified were 14 causative mutations, three
      of which were novel: one missense mutation (c.227T>G, p.V76G) and two splice-site
      mutations (c.78+1G>T and c.78+5G>A). No obvious genotype-phenotype relationship
      was observed. CONCLUSIONS: A missense mutation was the predominant type, and
      common or founder mutations were not observed in the Korean patients in this
      study who had XLRS. This study provides molecular genetic characteristics about
      an Asian population previously unexplored. The genetic characteristics of Korean
      XLRS will be helpful for understanding the worldwide spectrum of RS1 mutation.

PMID- 19390642
TI  - Release of 11-cis-retinal from cellular retinaldehyde-binding protein by acidic
      lipids.
AB  - PURPOSE: To determine molecular mechanisms for the release of 11-cis-retinal from
      the binding pocket of cellular retinaldehyde-binding protein (CRALBP). METHODS:
      Binding of CRALBP to lipid surfaces was assessed with a lipid-immunoblot assay.
      Lipids were presented to CRALBP as small unilamellar vesicles (SUVs) consisting
      of phosphatidylcholine (PC) plus other lipids. Release of 9-cis-retinal or 11-cis
      retinal from CRALBP was measured with spectral and high performance liquid
      chromatography (HPLC) assays based on the protection of the protein-bound retinal
      carbonyl group from reaction with NH(2)OH. The electrostatic surface potential of
      CRALBP was calculated from a model of its structure using the program CCP4mg.
      RESULTS: Incubation of CRALBP.11-cis-retinal with lipids absorbed on
      nitrocellulose revealed binding to the acidic lipids, phosphatidic acid
      (PA)>phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)]>phosphatidylserine
      (PS)> PI(4,5)P(2) and little or no binding to PC, phosphatidylethanolamine (PE),
      or PI(4)P. 11-cis-retinal was released during incubation of CRALBP with SUVs
      consisting of PC plus 50 mol% PA but not during incubation with those composed of
      100 mol% PC. The efficacy of release of 9-cis-retinal or 11-cis-retinal from
      CRALBP by phospholipid-containing SUVs generally paralleled that of the binding
      of CRALBP to the lipids (PA>PS>PI>>PC). Examination of the electrostatic surface
      potential of the protein structure revealed a basic recess on one face of the
      protein, which may bind acidic lipids. CONCLUSIONS: Our results identify the
      first physiologic substances that release 11-cis-retinal from CRALBP. PA and PS
      are relatively minor membrane lipids that can be generated in the cytoplasmic
      leaflet of the plasma membrane in response to various signal transduction
      pathways, where they could interact with cytosolic CRALBP. The mechanism for
      release of retinal from CRALBP by acidic lipids remains to be determined but
      could involve binding of the acidic lipid in the 11-cis-retinal binding site or
      to the positive basic recess on the protein surface. These results open a new
      facet in our understanding of how CRALBP functions in the regeneration of visual
      pigments.

PMID- 19390643
TI  - Alpha-tocopherol: looking beyond an antioxidant.
AB  - Vitamin E is an important natural antioxidant, and its most common and
      biologically active form is alpha-tocopherol. In addition to this, specific
      regulatory effects of vitamin E have been revealing. The body exerts a certain
      effort to regulate its tissue levels with specific tocopherol transport proteins
      and membrane receptors. Antiproliferative and protein kinase C-suppressing
      effects of alpha-tocopherol have been previously demonstrated, which have not
      been mimicked by beta-tocopherol or probucol. Protein kinase C promises to be an
      important area of interest in the means of glaucoma and cataractogenesis. It has
      been shown in different models that retinal vascular dysfunction due to
      hyperglycemia could be prevented by alpha-tocopherol via the diachylglycerol
      protein kinase C pathway. Glutamate transporter activity has been shown to be
      modulated by protein kinase C. This pathway is also important in intraocular
      pressure-lowering effects of prostaglandin and its analogs in glaucoma therapy.
      Filtran surgery became another possible area of usage of alpha-tocopherol since
      its antiproliferative effect has been demonstrated in human Tenon's capsule
      fibroblasts. Prevention of posterior capsule opacification is another area for
      future studies. It is evident that when correct and safe modulation is the
      objective, alpha-tocopherol merits a concern beyond its mere antioxidant
      properties.

PMID- 19390645
TI  - Is bagging effective in the classification of small-sample genomic and proteomic
      data?
AB  - There has been considerable interest recently in the application of bagging in
      the classification of both gene-expression data and protein-abundance mass
      spectrometry data. The approach is often justified by the improvement it produces
      on the performance of unstable, overfitting classification rules under small
      sample situations. However, the question of real practical interest is whether
      the ensemble scheme will improve performance of those classifiers sufficiently to
      beat the performance of single stable, nonoverfitting classifiers, in the case of
      small-sample genomic and proteomic data sets. To investigate that question, we
      conducted a detailed empirical study, using publicly-available data sets from
      published genomic and proteomic studies. We observed that, under t-test and
      RELIEF filter-based feature selection, bagging generally does a good job of
      improving the performance of unstable, overfitting classifiers, such as CART
      decision trees and neural networks, but that improvement was not sufficient to
      beat the performance of single stable, nonoverfitting classifiers, such as
      diagonal and plain linear discriminant analysis, or 3-nearest neighbors.
      Furthermore, as expected, the ensemble method did not improve the performance of
      these classifiers significantly. Representative experimental results are
      presented and discussed in this work.

PMID- 19390644
TI  - Pro370Leu mutant myocilin impairs mitochondrial functions in human trabecular
      meshwork cells.
AB  - PURPOSE: Oxidative stress is a risk factor for the onset and progression of
      primary open-angle glaucoma (POAG), but the exact molecular basis remains
      unknown. Here, we investigated the mechanisms for Pro370Leu mutant myocilin to
      induce mitochondrial dysfunction and subsequent reactive oxygen species (ROS)
      generation in trabecular meshwork (TM) cells obtained from POAG individuals.
      METHODS: Primary non-diseased human TM cultures were transfected with pIRES-EGFP
      (Mock), pIRES-wild-type (WT), or pIRES-Pro370Leu mutant myocilin. Transfection
      efficiency and myocilin subcellular localization were determined by polymerase
      chain reaction (PCR), western blot analysis, and confocal microscopy. ROS levels
      as well as free Ca(2+) concentrations in cytoplasm ([Ca(2+)](c)) and mitochondria
      ([Ca(2+)]m) were examined by 2'7'-dichlorofluorescein diacetate (H(2)-DCF-DA),
      Fluo-3 acetoxymethyl ester (Fluo-3/AM), and Rhod-2 acetoxymethyl ester (rhod
      2/AM), respectively, using flow cytometry. Mitochondrial functions were revealed
      by changes in mitochondrial membrane potential (DeltaPsim) and ATP production,
      which were found by fluorescent probe 5,5',6,6'-tetrachloro-1,1'3,3'
      tetraethylbenzimid azolocarbocyanine iodide (JC-1) and a luciferin/luciferase
      based ATP assay, respectively. RESULTS: Both WT and Pro370Leu mutant myocilin are
      localized in the mitochondria of TM cells as indicated using confocal microscopy
      and western blot analysis. Overexpression of WT myocilin decreases DeltaPsim,
      which is further reduced by Pro370Leu mutant myocilin. TM cells that
      overexpressed Pro370Leu mutant myocilin have greater cell death, higher
      endogenous ROS, [Ca(2+)](c), and [Ca(2+)](m) levels, and lower ATP production,
      and yet, these effects are not seen in the overexpression of WT myocilin.
      CONCLUSIONS: Our findings suggested that Pro370Leu mutant myocilin causes
      mitochondrial defects, which may lead to TM cell dysfunction and even cell death.
      Therefore, preventive measures targeting mitochondrial protection may delay the
      onset of glaucoma in individuals carrying the Pro370Leu myocilin mutation.

PMID- 19390646
TI  - Evaluation and management of patients with noncardiac chest pain.
AB  - Up to a third of patients undergoing coronary angiography for angina-like chest
      pain are found to have normal coronary arteries and a substantial proportion of
      these individuals continue to consult and even attend emergency departments.
      Initially, these patients are usually seen by cardiologists but with accumulating
      evidence that the pain might have a gastrointestinal origin, it may be more
      appropriate for them to be cared for by the gastroenterologist once a
      cardiological cause has been excluded. This review covers the assessment and
      management of this challenging condition, which includes a combination of
      education, reassurance, and pharmacotherapy. For the more refractory cases,
      behavioral treatments, such as cognitive behavioral therapy or hypnotherapy, may
      have to be considered.

PMID- 19390647
TI  - Effects of ubiquinol-10 on microRNA-146a expression in vitro and in vivo.
AB  - MicroRNAs (miRs) are involved in key biological processes via suppression of gene
      expression at posttranscriptional levels. According to their superior functions,
      subtle modulation of miR expression by certain compounds or nutrients is
      desirable under particular conditions. Bacterial lipopolysaccharide (LPS) induces
      a reactive oxygen species-/NF-kappaB-dependent pathway which increases the
      expression of the anti-inflammatory miR-146a. We hypothesized that this induction
      could be modulated by the antioxidant ubiquinol-10. Preincubation of human
      monocytic THP-1 cells with ubiquinol-10 reduced the LPS-induced expression level
      of miR-146a to 78.9 +/- 13.22%. In liver samples of mice injected with LPS,
      supplementation with ubiquinol-10 leads to a reduction of LPS-induced miR-146a
      expression to 78.12 +/- 21.25%. From these consistent in vitro and in vivo data,
      we conclude that ubiquinol-10 may fine-tune the inflammatory response via
      moderate reduction of miR-146a expression.

PMID- 19390648
TI  - Dietary modulation of inflammation-induced colorectal cancer through PPARgamma.
AB  - Mounting evidence suggests that the risk of developing colorectal cancer (CRC) is
      dramatically increased for patients with chronic inflammatory diseases. For
      instance, patients with Crohn's Disease (CD) or Ulcerative Colitis (UC) have a 12
      20% increased risk for developing CRC. Preventive strategies utilizing nontoxic
      natural compounds that modulate immune responses could be successful in the
      suppression of inflammation-driven colorectal cancer in high-risk groups. The
      increase of peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      expression and its transcriptional activity has been identified as a target for
      anti-inflammatory efforts, and the suppression of inflammation-driven colon
      cancer. PPARgamma down-modulates inflammation and elicits antiproliferative and
      proapoptotic actions in epithelial cells. All of which may decrease the risk for
      inflammation-induced CRC. This review will focus on the use of orally active,
      naturally occurring chemopreventive approaches against inflammation-induced CRC
      that target PPARgamma and therefore down-modulate inflammation.

PMID- 19390649
TI  - PPAR and liver injury in HIV-infected patients.
AB  - Due to the introduction of active HIV antiretroviral treatment, AIDS-related
      morbidity and mortality have markedly decreased and liver diseases are now a
      major cause of morbidity and mortality in HIV-infected patients. Chronic liver
      injury encompasses a wide spectrum of diseases due to HCV and HBV coinfection,
      drug-related toxicity, and NASH. HIV-infected patients who are receiving
      treatment present with a high prevalence of metabolic complications and
      lipodystrophy. Those patients are at high risk of nonalcoholic fatty liver
      disease, the liver feature of the metabolic syndrome. This review will focus on
      (1) the liver injuries in HIV-infected patients; (2) both the current
      experimental and human data regarding PPAR and liver diseases; (3) the
      interactions between HIV and PPAR; (4) the potential use of PPAR agonists for the
      management of HIV-related liver diseases.

PMID- 19390650
TI  - Cell survival from chemotherapy depends on NF-kappaB transcriptional up
      regulation of coenzyme Q biosynthesis.
AB  - BACKGROUND: Coenzyme Q (CoQ) is a lipophilic antioxidant that is synthesized by a
      mitochondrial complex integrated by at least ten nuclear encoded COQ gene
      products. CoQ increases cell survival under different stress conditions,
      including mitochondrial DNA (mtDNA) depletion and treatment with cancer drugs
      such as camptothecin (CPT). We have previously demonstrated that CPT induces CoQ
      biosynthesis in mammal cells. METHODOLOGY/PRINCIPAL FINDINGS: CPT activates NF
      kappaB that binds specifically to two kappaB binding sites present in the 5'
      flanking region of the COQ7 gene. This binding is functional and induces both the
      COQ7 expression and CoQ biosynthesis. The inhibition of NF-kappaB activation
      increases cell death and decreases both, CoQ levels and COQ7 expression induced
      by CPT. In addition, using a cell line expressing very low of NF-kappaB, we
      demonstrate that CPT was incapable of enhancing enhance both CoQ biosynthesis and
      COQ7 expression in these cells. CONCLUSIONS/SIGNIFICANCE: We demonstrate here,
      for the first time, that a transcriptional mechanism mediated by NF-kappaB
      regulates CoQ biosynthesis. This finding contributes new data for the
      understanding of the regulation of the CoQ biosynthesis pathway.

PMID- 19390651
TI  - Impact of hepatitis B exposure on sustained virological response rates of highly
      viremic chronic hepatitis C patients.
AB  - AIM: To evaluate the impact of hepatitis B core antibody (anti-HBc)
      seropositivity in sustained virological response (SVR) rates in treatment-naive,
      chronic hepatitis C (CHC) patients with high pretreatment viral load (>800000
      IU/mL). METHODS: 185 consecutive CHC patients (14.4% cirrhotics, 70.2% prior
      intravenous drug users) treated with pegylated interferon-a2b plus ribavirin, for
      24 or 48 weeks based on viral genotype, were retrospectively analyzed. SVR was
      confirmed by undetectable serum HCV-RNA six months after the end of treatment
      schedule. RESULTS: Thirty percent of CHC/HBsAg-negative patients were anti-HBc
      positive. Anti-HBc positivity was more prevalent in cirrhotic, compared to
      noncirrhotic patients (76.9% versus 19.5%, P < .05). Serum HBV-DNA was detected
      in the minority of anti-HBc-positive patients (1.97%). Overall, 62.1% of patients
      exhibited SVR, while 28.6% did not; 71.4% of non-SVRs were infected with genotype
      1. In the univariate analysis, the anti-HBc positivity was negatively associated
      with treatment outcome (P = .065). In the multivariate model, only the advanced
      stage of liver disease (P = .015) and genotype-1 HCV infection (P = .003), but
      not anti-HBc-status (P = .726), proved to be independent predictors of non-SVR.
      CONCLUSION: Serum anti-HBc positivity does not affect the SVR rates in treatment
      naive CHC patients with high pretreatment viral load, receiving the currently
      approved combination treatment.

PMID- 19390652
TI  - Mutation analysis of CRYAA, CRYGC, and CRYGD associated with autosomal dominant
      congenital cataract in Brazilian families.
AB  - PURPOSE: Congenital cataracts are one of the most treatable causes of visual
      impairment and blindness during infancy. Approximately 50% of all congenital
      cataract cases may have a genetic cause. Once there is an intimate relationship
      between crystallin genes and lens transparency, they are excellent candidate
      genes for inherited cataract. The purpose of this study was to investigate
      mutations in alphaA-crystallin (CRYAA), gammaC-crystallin (CRYGC), and gammaD
      crystallin (CRYGD) in Brazilian families with nuclear and lamellar autosomal
      dominant congenital cataract. METHODS: Eleven Brazilian families were referred to
      the Santa Casa de Sao Paulo Ophthalmology Department. The coding regions and
      intron/exon boundaries of CRYAA, CRYGC, and CRYGD were amplified by polymerase
      chain reaction (PCR) and directly sequenced. Mutation screening was performed in
      the control group by restriction digestion. RESULTS: Two mutations were observed
      in different families (Family 4 and Family 10), one is a new mutation (Y56X) in
      CRYGD and the other a previously reported mutation (R12C) in CRYAA that is
      correlated with a different phenotype. Genetic analysis revealed previously
      described polymorphisms in CRYAA (D2D) and CRYGD (Y17Y and R95R). A new
      polymorphism in CRYGC (S119S) was identified only in Family 1. The mutations as
      well as the new polymorphism were not observed in the control group. CONCLUSIONS:
      In conclusion, we report a novel nonsense mutation (Y56X) in CRYGD and a
      previously reported missense mutation (R12C) in CRYAA associated with nuclear
      cataract in Brazilian families. Both tyrosine in amino acid 56 in CRYGD and
      arginine in amino acid 12 in CRYAA have been highly conserved throughout
      evolution in different species. A new polymorphism (S119S) in CRYGC was also
      observed in one family. The analysis of nine families excluded possible mutations
      in the crystallin genes, suggesting that other genes could be involved with
      congenital cataract.

PMID- 19390653
TI  - Ocular expression of avian thymic hormone: changes during the recovery from
      induced myopia.
AB  - PURPOSE: Several studies suggest that postnatal ocular growth is under the
      control of factors within the eye that regulate the rate of scleral extracellular
      matrix remodeling and the rate of ocular elongation. A microarray analysis was
      employed to identify some of the factors involved in the regulation of visually
      guided ocular growth. Gene expression was compared in the retina-retinal
      pigmented epithelium (RPE)-choroid of chick eyes that were decelerating in the
      rate of ocular growth ("recovering" from myopia) as compared with contralateral
      control eyes. METHODS: Form-deprivation myopia was induced in the right eyes of
      two-day-old chicks by the application of translucent occluders. Following 10 days
      of deprivation, occluders were removed and chicks were provided unrestricted
      vision for an additional 1-7 days (recovery). After one and four days of
      recovery, chicks were sacrificed, retina, RPE, and choroid were isolated, and
      mRNA was subjected to microarray analysis using a chicken immune system 4000 gene
      microarray. In addition, whole eyes and isolated ocular tissues (retina and RPE,
      choroid, sclera, and extraocular muscle) of treated and control eyes were
      subjected to real-time PCR, immunohistochemistry, and western blot analyses to
      verify gene expression results. RESULTS: Following one day of recovery, only one
      gene, avian thymic hormone (ATH) was highly upregulated (+12.3 fold). ATH gene
      and protein expression were confirmed in the retina and choroid as well as in the
      sclera and extraocular muscle. A significant increase in ATH protein was detected
      in choroids from treated eyes following four days of recovery as compared to
      contralateral controls (p<0.05; Wilcoxon signed-rank test). CONCLUSIONS: ATH is
      expressed in several ocular tissues and is specifically and rapidly (within one
      day) upregulated in the choroids of chick eyes recovering from induced myopia.
      This upregulation corresponds to the onset of choroidal thickening and increased
      choroidal vascular permeability. The identification of ATH in ocular tissues and
      its increased protein accumulation in the choroid during recovery from induced
      myopia suggest a novel role for this protein in the choroidal response to myopic
      defocus.

PMID- 19390654
TI  - Germline mutations in retinoma patients: relevance to low-penetrance and low
      expressivity molecular basis.
AB  - PURPOSE: To study phenotype-genotype correlation in patients who have retinoma,
      which is a benign tumor resembling the post irradiation regression pattern of
      retinoblastoma (RB). METHODS: We selected patients who had retinoma and positive
      family history for RB and patients who had retinoma in one eye and either
      retinoma or RB in the other eye. The study included 22 patients with available
      DNA: 18 from 11 families and four sporadic cases. DNA was extracted from
      peripheral blood leukocytes. The RB1 gene was screened by DHPLC and direct
      sequencing of the promoter and all the exons. RESULTS: We identified 17
      occurrences of 11 distinct germline mutations in two sporadic and in 15 familial
      cases (nine families). The 11 identified mutations were located in exons 1,
      10,11,13,14, and 19 to 23. Four of the identified mutations were not previously
      reported, including g.64407delT, g.153236A>T, g.156743delTCTG, and g.162078delA.
      Eight out the 11 mutations were truncating and three were nontruncating
      (missense). There was no correlation between the type of mutation and the number
      of tumor foci per eye (RB or retinomas). Highly heterogeneous intrafamilial
      expressivity was observed. CONCLUSIONS: To our knowledge, this study is the
      largest series of mutations of consecutive retinoma patients. The present data
      suggest that the type of inherited mutations underlying retinoma is
      undistinguishable from RB related ones, i.e., largely dominated by truncating
      mutants. This finding is in contrast with the RB1 genotypic spectrum of mutations
      associated with low-penetrance RB, i.e., nontruncating mutants. The molecular
      mechanism underlying low-penetrance and attenuated expressivity (retinomas)
      appeared to be distinct.

PMID- 19390655
TI  - Novel pathogenic mutations and skin biopsy analysis in Knobloch syndrome.
AB  - PURPOSE: To facilitate future diagnosis of Knobloch syndrome (KS) and better
      understand its etiology, we sought to identify not yet described COL18A1
      mutations in KS patients. In addition, we tested whether mutations in this gene
      lead to absence of the COL18A1 gene product and attempted to better characterize
      the functional effect of a previously reported missense mutation. METHODS: Direct
      sequencing of COL18A1 exons was performed in KS patients from four unrelated
      pedigrees. We used immunofluorescent histochemistry in skin biopsies to evaluate
      the presence of type XVIII collagen in four KS patients carrying two already
      described mutations: c.3277C>T, a nonsense mutation, and c.3601G>A, a missense
      mutation. Furthermore, we determined the binding properties of the mutated
      endostatin domain p.A1381T (c.3601G>A) to extracellular matrix proteins using
      ELISA and surface plasmon resonance assays. RESULTS: We identified four novel
      mutations in COL18A1, including a large deletion involving exon 41. Skin biopsies
      from KS patients revealed lack of type XVIII collagen in epithelial basement
      membranes and blood vessels. We also found a reduced affinity of p.A1381T
      endostatin to some extracellular matrix components. CONCLUSIONS: COL18A1
      mutations involved in Knobloch syndrome have a distribution bias toward the
      coding exons of the C-terminal end. Large deletions must also be considered when
      point mutations are not identified in patients with characteristic KS phenotype.
      We report, for the first time, lack of type XVIII collagen in KS patients by
      immunofluorescent histochemistry in skin biopsy samples. As a final point, we
      suggest the employment of this technique as a preliminary and complementary test
      for diagnosis of KS in cases when mutation screening either does not detect
      mutations or reveals mutations of uncertain effect, such as the p.A1381T change.

PMID- 19390656
TI  - A novel GPR143 duplication mutation in a Chinese family with X-linked congenital
      nystagmus.
AB  - PURPOSE: To elucidate the molecular genetic defect of X-linked congenital
      nystagmus in a Chinese family. METHODS: Genomic DNA was prepared from peripheral
      blood. We used allele-sharing analysis to identify the possible locus harboring
      the disease-causing gene. We screened for mutations in the G protein-coupled
      receptor 143 gene (GPR143) by direct sequencing of the polymerase chain reaction
      (PCR)-amplified exons. RESULTS: In analyzing the candidate gene, GPR143, in the
      linked region, a 19 base pair (bp) duplication mutation in exon 1 was detected
      after direct DNA sequence analysis, which cosegregated in all patients of this
      family and was present in obligate female carriers. CONCLUSIONS: The identified
      19 bp duplication in GPR143 induces a frame-shift and a premature stop codon,
      resulting in a truncated protein of 105 residues. These results suggest that this
      novel mutation is associated with the congenital nystagmus observed in this
      Chinese family and further support that GPR143 mutations are the underlying
      pathogenesis of the molecular mechanism for congenital nystagmus.

PMID- 19390657
TI  - Pathologic prion protein infects cells by lipid-raft dependent macropinocytosis.
AB  - Transmissible spongiform encephalopathies, including variant-Creutzfeldt-Jakob
      disease (vCJD) in humans and bovine spongiform encephalopathies in cattle, are
      fatal neurodegenerative disorders characterized by protein misfolding of the host
      cellular prion protein (PrP(C)) to the infectious scrapie form (PrP(Sc)).
      However, the mechanism that exogenous PrP(Sc) infects cells and where pathologic
      conversion of PrP(C) to the PrP(Sc) form occurs remains uncertain. Here we report
      that similar to the mechanism of HIV-1 TAT-mediated peptide transduction,
      processed mature, full length PrP contains a conserved N-terminal cationic domain
      that stimulates cellular uptake by lipid raft-dependent, macropinocytosis.
      Inhibition of macropinocytosis by three independent means prevented cellular
      uptake of recombinant PrP; however, it did not affect recombinant PrP cell
      surface association. In addition, fusion of the cationic N-terminal PrP domain to
      a Cre recombinase reporter protein was sufficient to promote both cellular uptake
      and escape from the macropinosomes into the cytoplasm. Inhibition of
      macropinocytosis was sufficient to prevent conversion of PrP(C) to the pathologic
      PrP(Sc) form in N2a cells exposed to strain RML PrP(Sc) infected brain
      homogenates, suggesting that a critical determinant of PrP(C) conversion occurs
      following macropinocytotic internalization and not through mere membrane
      association. Taken together, these observations provide a cellular mechanism that
      exogenous pathological PrP(Sc) infects cells by lipid raft dependent,
      macropinocytosis.

PMID- 19390658
TI  - Transcriptional network of p63 in human keratinocytes.
AB  - p63 is a transcription factor required for the development and maintenance of
      ectodermal tissues in general, and skin keratinocytes in particular. The
      identification of its target genes is fundamental for understanding the complex
      network of gene regulation governing the development of epithelia. We report a
      list of almost 1000 targets derived from ChIP on chip analysis on two platforms;
      all genes analyzed changed in expression during differentiation of human
      keratinocytes. Functional annotation highlighted unexpected GO terms enrichments
      and confirmed that genes involved in transcriptional regulation are the most
      significant. A detailed analysis of these transcriptional regulators in condition
      of perturbed p63 levels confirmed the role of p63 in the regulatory network.
      Rather than a rigid master-slave hierarchical model, our data indicate that p63
      connects different hubs involved in the multiple specific functions of the skin.

PMID- 19390659
TI  - Change detection & characterization: a new tool for imaging informatics and
      cancer research.
AB  - Modern imaging systems are able to produce a rich and diverse array of
      information, regarding various facets of anatomy and function. The quantity of
      information produced by these systems is so bountiful, however, as to have the
      potential to become a hindrance to clinical assessment. In the context of serial
      image evaluation, computer-based change detection and characterization is one
      important mechanism to process the information produced by imaging systems, so as
      to reduce the quantity of data, direct the attention of the physician to regions
      of the data which are the most informative for their purposes, and present the
      data in the form in which it will be the most useful. Change detection and
      characterization algorithms may serve as a basis for the creation of an objective
      definition of progression, which will reduce inter and intra-observer
      variability, and facilitate earlier detection of disease and recurrence, which in
      turn may lead to improved outcomes. Decreased observer variability combined with
      increased acuity should make it easier to discover promising therapies.
      Quantitative measures of the response to these therapies should provide a means
      to compare the effectiveness of treatments under investigation. Change detection
      may be applicable to a broad range of cancers, in essentially all anatomical
      regions. The source of information upon which change detection comparisons may be
      based is likewise broad. Validation of algorithms for the longitudinal assessment
      of cancer patients is expected to be challenging, though not insurmountable, as
      the many facets of the problem mean that validation will likely need to be
      approached from a variety of vantage points. Change detection and
      characterization is quickly becoming a very active field of investigation, and it
      is expected that this burgeoning field will help to facilitate cancer care both
      in the clinic and research.

PMID- 19390660
TI  - Imaging in clinical trials.

PMID- 19390661
TI  - Image registration improves confidence and accuracy of image interpretation.

PMID- 19390662
TI  - An architecture for computer-aided detection and radiologic measurement of lung
      nodules in clinical trials.
AB  - Computer tomography (CT) imaging plays an important role in cancer detection and
      quantitative assessment in clinical trials. High-resolution imaging studies on
      large cohorts of patients generate vast data sets, which are infeasible to
      analyze through manual interpretation. In this article we describe a
      comprehensive architecture for computer-aided detection (CAD) and surveillance on
      lung nodules in CT images. Central to this architecture are the analytic
      components: an automated nodule detection system, nodule tracking capabilities
      and volume measurement, which are integrated within a data management system that
      includes mechanisms for receiving and archiving images, a database for storing
      quantitative nodule measurements and visualization, and reporting tools. We
      describe two studies to evaluate CAD technology within this architecture, and the
      potential application in large clinical trials. The first study involves
      performance assessment of an automated nodule detection system and its ability to
      increase radiologist sensitivity when used to provide a second opinion. The
      second study investigates nodule volume measurements on CT made using a semi
      automated technique and shows that volumetric analysis yields significantly
      different tumor response classifications than a 2D diameter approach. These
      studies demonstrate the potential of automated CAD tools to assist in
      quantitative image analysis for clinical trials.

PMID- 19390663
TI  - DICOM structured reporting and cancer clinical trials results.
AB  - The use of biomarkers derived from radiological images as surrogate end-points in
      therapeutic cancer clinical trials is well established. DICOM is the ubiquitous
      standard for the interchange of images for both clinical use as well as research.
      It also has capabilities for the exchange of image-related information, including
      categorical and quantitative information derived from images. The use of DICOM
      Structured Reporting for the encoding and interchange of clinical trial results
      in a standard manner is reviewed.

PMID- 19390664
TI  - Advancing cancer systems biology: introducing the Center for the Development of a
      Virtual Tumor, CViT.
AB  - Integrative cancer biology research relies on a variety of data-driven
      computational modeling and simulation methods and techniques geared towards
      gaining new insights into the complexity of biological processes that are of
      critical importance for cancer research. These include the dynamics of gene
      protein interaction networks, the percolation of sub-cellular perturbations
      across scales and the impact they may have on tumorigenesis in both experiments
      and clinics. Such innovative 'systems' research will greatly benefit from
      enabling Information Technology that is currently under development, including an
      online collaborative environment, a Semantic Web based computing platform that
      hosts data and model repositories as well as high-performance computing access.
      Here, we present one of the National Cancer Institute's recently established
      Integrative Cancer Biology Programs, i.e. the Center for the Development of a
      Virtual Tumor, CViT, which is charged with building a cancer modeling community,
      developing the aforementioned enabling technologies and fostering multi-scale
      cancer modeling and simulation.

PMID- 19390665
TI  - Cancer as a system failure.

PMID- 19390666
TI  - Exploratory Visual Analysis of statistical results from microarray experiments
      comparing high and low grade glioma.
AB  - The biological interpretation of gene expression microarray results is a daunting
      challenge. For complex diseases such as cancer, wherein the body of published
      research is extensive, the incorporation of expert knowledge provides a useful
      analytical framework. We have previously developed the Exploratory Visual
      Analysis (EVA) software for exploring data analysis results in the context of
      annotation information about each gene, as well as biologically relevant groups
      of genes. We present EVA as a flexible combination of statistics and biological
      annotation that provides a straightforward visual interface for the
      interpretation of microarray analyses of gene expression in the most commonly
      occurring class of brain tumors, glioma. We demonstrate the utility of EVA for
      the biological interpretation of statistical results by analyzing publicly
      available gene expression profiles of two important glial tumors. The results of
      a statistical comparison between 21 malignant, high-grade glioblastoma multiforme
      (GBM) tumors and 19 indolent, low-grade pilocytic astrocytomas were analyzed
      using EVA. By using EVA to examine the results of a relatively simple statistical
      analysis, we were able to identify tumor class-specific gene expression patterns
      having both statistical and biological significance. Our interactive analysis
      highlighted the potential importance of genes involved in cell cycle progression,
      proliferation, signaling, adhesion, migration, motility, and structure, as well
      as candidate gene loci on a region of Chromosome 7 that has been implicated in
      glioma. Because EVA does not require statistical or computational expertise and
      has the flexibility to accommodate any type of statistical analysis, we
      anticipate EVA will prove a useful addition to the repertoire of computational
      methods used for microarray data analysis. EVA is available at no charge to
      academic users and can be found at http://www.epistasis.org.

PMID- 19390668
TI  - Perturbation of interaction networks for application to cancer therapy.
AB  - We present a computational approach for studying the effect of potential drug
      combinations on the protein networks associated with tumor cells. The majority of
      therapeutics are designed to target single proteins, yet most diseased states are
      characterized by a combination of many interacting genes and proteins. Using the
      topology of protein-protein interaction networks, our methods can explicitly
      model the possible synergistic effect of targeting multiple proteins using drug
      combinations in different cancer types. The methodology can be conceptually split
      into two distinct stages. Firstly, we integrate protein interaction and gene
      expression data to develop network representations of different tissue types and
      cancer types. Secondly, we model network perturbations to search for target
      combinations which cause significant damage to a relevant cancer network but only
      minimal damage to an equivalent normal network. We have developed sets of
      predicted target and drug combinations for multiple cancer types, which are
      validated using known cancer and drug associations, and are currently in
      experimental testing for prostate cancer. Our methods also revealed significant
      bias in curated interaction data sources towards targets with associations
      compared with high-throughput data sources from model organisms. The approach
      developed can potentially be applied to many other diseased cell types.

PMID- 19390667
TI  - Application of gene shaving and mixture models to cluster microarray gene
      expression data.
AB  - Researchers are frequently faced with the analysis of microarray data of a
      relatively large number of genes using a small number of tissue samples. We
      examine the application of two statistical methods for clustering such microarray
      expression data: EMMIX-GENE and GeneClust. EMMIX-GENE is a mixture-model based
      clustering approach, designed primarily to cluster tissue samples on the basis of
      the genes. GeneClust is an implementation of the gene shaving methodology,
      motivated by research to identify distinct sets of genes for which variation in
      expression could be related to a biological property of the tissue samples. We
      illustrate the use of these two methods in the analysis of Affymetrix
      oligonucleotide arrays of well-known data sets from colon tissue samples with and
      without tumors, and of tumor tissue samples from patients with leukemia. Although
      the two approaches have been developed from different perspectives, the results
      demonstrate a clear correspondence between gene clusters produced by GeneClust
      and EMMIX-GENE for the colon tissue data. It is demonstrated, for the case of
      ribosomal proteins and smooth muscle genes in the colon data set, that both
      methods can classify genes into co-regulated families. It is further demonstrated
      that tissue types (tumor and normal) can be separated on the basis of subtle
      distributed patterns of genes. Application to the leukemia tissue data produces a
      division of tissues corresponding closely to the external classification, acute
      myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), for both methods.
      In addition, we also identify genes specific for the subgroup of ALL-Tcell
      samples. Overall, we find that the gene shaving method produces gene clusters at
      great speed; allows variable cluster sizes and can incorporate partial or full
      supervision; and finds clusters of genes in which the gene expression varies
      greatly over the tissue samples while maintaining a high level of coherence
      between the gene expression profiles. The intent of the EMMIX-GENE method is to
      cluster the tissue samples. It performs a filtering step that results in a subset
      of relevant genes, followed by gene clustering, and then tissue clustering, and
      is favorable in its accuracy of ranking the clusters produced.

PMID- 19390669
TI  - The evolution of transdermal/topical overactive bladder therapy and its benefits
      over oral therapy.
AB  - Multiple antimuscarinic agents are available for the treatment of overactive
      bladder. Many of the agents have undergone reformulation in an attempt to improve
      patient adherence and drug tolerability. Oxybutynin evolved from an immediate
      release pill to a once-daily oral preparation, and is now available as a
      transdermal patch and gel. This article discusses the clinical impact of
      oxybutynin reformulation and reviews the evolution and benefits of transdermal
      therapy.

PMID- 19390670
TI  - Robotic image-guided needle interventions of the prostate.
AB  - Prostate biopsy and needle-directed prostate therapies are currently performed
      free-handed or with needle external templates under ultrasound guidance. Direct
      image-guided intervention robots are modern instruments that have the potential
      to substantially enhance these procedures. These may increase the accuracy and
      repeatability with which needles are placed in the gland. The authors' group has
      developed a robot for precise prostate targeting that operates remotely alongside
      the patient in the magnetic resonance imaging scanner, as guided according to the
      image.

PMID- 19390671
TI  - The role of immunotherapy in prostate cancer: an overview of current approaches
      in development.
AB  - Ongoing clinical trials provide promise for the introduction of immunotherapy
      into the armamentarium against prostate cancer, but the precise role for
      immunotherapy remains to be determined. Combinations of immunotherapies may be
      needed to improve the response rates and the duration of response. Investigators
      have begun to examine the effect of immunotherapy in combination with other
      standard treatment, including as an adjuvant to chemotherapy or radiotherapy and
      as a neoadjuvant agent before prostatectomy. Although many studies examine
      efficacy in men with metastatic hormone-refractory prostate cancer, there is some
      evidence for improved responses at earlier stages of disease: the ability of the
      tumor to evade the immune system may be lessened with lower tumor burden, or the
      immune system may already be weakened in men with later stages of disease.

PMID- 19390672
TI  - Treatment of painful bladder syndrome and pelvic organ prolapse: highlights of
      the 4th international consultation on incontinence, july 5-8, 2008, paris,
      france.

PMID- 19390673
TI  - Renal involvement by chronic myelomonocytic leukemia requiring
      nephroureterectomy.
AB  - Chronic monomyelocytic leukemia (CMML) is a relatively rare clonal hematologic
      disorder with features of myelodysplastic syndrome and myeloproliferative
      disease. Renal impairment from CMML is infrequent and can result from both direct
      (ie, infiltrative) and indirect (eg, vasculitis, infarction) mechanisms. This
      case report describes a patient with refractory gross hematuria requiring
      nephroureterectomy with diffuse involvement of the upper tract by CMML and
      accompanying extramedullary hematopoiesis. Underscored are the need to maintain a
      broad differential diagnosis for upper tract lesions in the setting of gross
      hematuria, and the potential need for drastic measures to control upper tract
      bleeding if conservative measures fail.

PMID- 19390674
TI  - Pediatric urology.

PMID- 19390675
TI  - Ejaculation-the long and short of it.

PMID- 19390676
TI  - Stress incontinence and prolapse therapy assessment.

PMID- 19390677
TI  - Editorial: Focusing on What Matters most-Quality Chiropractic Education.

PMID- 19390678
TI  - Generalizability of a composite student selection procedure at a university-based
      chiropractic program.
AB  - PURPOSE: Non-cognitive admission criteria are typically used in chiropractic
      student selection to supplement grades. The reliability of non-cognitive student
      admission criteria in chiropractic education has not previously been examined. In
      addition, very few studies have examined the overall test generalizability of
      composites of non-cognitive admission variables in admission to health science
      programs. The aim of this study was to estimate the generalizability of a
      composite selection to a chiropractic program, consisting of: application form
      information, a written motivational essay, a common knowledge test, and an
      admission interview. METHODS: Data from 105 Chiropractic applicants from the 2007
      admission at the University of Southern Denmark were available for analysis. Each
      admission parameter was double scored using two random, blinded, and independent
      raters. Variance components for applicant, rater and residual effects were
      estimated for a mixed model with the restricted maximum likelihood method. The
      reliability of obtained applicant ranks (generalizability coefficients) was
      calculated for the individual admission criteria and for the composite admission
      procedure. RESULTS: Very good generalizability was found for the common knowledge
      test (G=1.00) and the admission interview (G=0.88). Good generalizability was
      found for application form information (G=0.75) and moderate generalizability
      (G=0.50) for the written motivation essay. The generalizability of the final
      composite admission procedure, which was a weighted composite of all 4 admission
      variables was good (G(c) = 0.80). CONCLUSION: Good generalizability for a
      composite admission to a chiropractic program was found. Optimal weighting and
      adequate sampling are important for obtaining optimal generalizability.
      Limitations and suggestions for future research are discussed.

PMID- 19390679
TI  - Intentions of Chiropractic Interns Regarding use of Health Promotion in Practice:
      Applying Theory of Reasoned Action to Identify Attitudes, Beliefs, and
      Influencing Factors.
AB  - PURPOSE: The theory of reasoned action is a health behavioral theory that has
      been used to predict personal health behaviors and intentions as well as those of
      providers delivering health care. The purpose of this study was to determine
      interns' future practices regarding the use of health promotion using this model
      to develop survey questions and to determine attitudes and perceived influences
      on their prospective behaviors in general, toward the use of health promotion
      once in practice. METHODS: Across the course of one year, all graduating interns
      at a chiropractic college were queried with a 20 question survey designed using
      the theory of reasoned action. Frequencies and inferential statistics were
      performed including prediction modeling using logistic regression. RESULTS: A
      majority (>85%) of interns indicated they would use health promotion in practice.
      Differences were noted based on perceived skill levels, perception of educational
      emphasis, various normative beliefs, and gender. CONCLUSION: Most interns will
      use some form of health promotion in practice. Normative influences including
      those seen as key influencers are as powerful a predictor as perceived education
      or skill levels on future practice of health promotion.

PMID- 19390680
TI  - A survey of geriatrics courses in north american chiropractic programs.
AB  - PURPOSE: There has been a growing interest in meeting the health care needs of
      the anticipated "age wave." In order to prepare for the current demographic
      trends, we sought to describe the status of geriatrics curricula in the 18 North
      American English-speaking chiropractic colleges by reviewing geriatric course
      syllabi. METHODS: A cross-sectional survey was conducted using syllabi and
      catalog information solicited from each English-speaking chiropractic college in
      North America, collected from January 1, 2007 through June 30, 2007. Information
      was then summarized. RESULTS: As of June 30, 2007, roughly 78% of colleges
      submitted their current geriatrics course syllabi. The remaining 4 colleges were
      estimated using online course catalog information. Sixty-one percent of colleges
      offered a course that was solely dedicated to the topic of geriatrics.
      Additionally, 37.5% of syllabi indicating credit load offer 4 or more credits to
      the course containing the geriatrics component. Also, 31.3% of courses include
      non-classroom clinical experience, while 50% require an independent study project
      that provides further geriatrics experience. Furthermore, 41.2% of reported
      courses classify the teaching strategies as lecture only. CONCLUSIONS: These
      results warrant a proposal for improved curricula in this specialty population.
      It is proposed that more time be dedicated for this topic, more experiential
      learning be required, and more clinical focus be given on the needs of this
      population. A restructure of curricula will provide more clinical experiences for
      students to better equip future doctors of chiropractic for the increase in
      geriatric health care needs.

PMID- 19390681
TI  - Managing conflicts of interest in continuing medical education: a comparison of
      policies.
AB  - BACKGROUND: Altruism is a central underpinning of professional behavior; however
      physicians may face instances in which their secondary (financial) interest is in
      competition with their primary (patient health, research integrity, professional
      education) interests. Most medical institutions have developed policies to manage
      conflicts of interest, but chiropractic institutions, organizations and providers
      may not be well-acquainted with such policies. PURPOSE: To compare the policies
      of the Department of Veterans Affairs (VA) and the North American Spine Society
      (NASS) regarding management of conflicts of interest in continuing medical
      education (CME). METHODS: A qualitative review of published policies of the VA
      and NASS was performed. The policies of each organization were retrieved and
      reviewed, and data were entered into a spreadsheet for comparison. Content
      experts at each organization were contacted to provide additional information.
      RESULTS: The VA and NASS provide explicit, similar policies to manage conflicts
      of interest in CME. Proposed speakers are required to disclose the nature and
      value of financial relationships relevant to content of their planned
      talk/presentation. Procedures for committee review, mitigation of conflict, or
      prohibiting the participation of a given speaker have been described. Disclosure
      must be made to the attendees of an educational activity in printed materials and
      at the time of presentation. CONCLUSION: The VA and NASS appear similar in their
      policies to manage conflicts of interest in CME. The policies of the VA and NASS
      may provide examples for the chiropractic profession to consider in relation to
      chiropractic continuing education.

PMID- 19390682
TI  - The Implementation of Virtual Instruction in Relation to X-ray Anatomy and
      Positioning in a Chiropractic Degree Program: A Descriptive Paper.
AB  - This article provides information regarding the introduction of virtual education
      into classroom instruction, wherein a method of classroom instruction was
      developed with the use of a computer, digital camera, and various software
      programs. This approach simplified testing procedures, thus reducing
      institutional costs substantially by easing the demand for manpower, and seemed
      to improve average grade performance. Organized files with hundreds of digital
      pictures have created a range of instructor resources. Much of the new course
      materials were organized onto compact disks to complement course notes.
      Customizing presentations with digital technology holds potential benefits for
      students, instructors and the institution.

PMID- 19390684
TI  - Efficient alignment of RNAs with pseudoknots using sequence alignment
      constraints.
AB  - When aligning RNAs, it is important to consider both the secondary structure
      similarity and primary sequence similarity to find an accurate alignment.
      However, algorithms that can handle RNA secondary structures typically have high
      computational complexity that limits their utility. For this reason, there have
      been a number of attempts to find useful alignment constraints that can reduce
      the computations without sacrificing the alignment accuracy. In this paper, we
      propose a new method for finding effective alignment constraints for fast and
      accurate structural alignment of RNAs, including pseudoknots. In the proposed
      method, we use a profile-HMM to identify the "seed" regions that can be aligned
      with high confidence. We also estimate the position range of the aligned bases
      that are located outside the seed regions. The location of the seed regions and
      the estimated range of the alignment positions are then used to establish the
      sequence alignment constraints. We incorporated the proposed constraints into the
      profile context-sensitive HMM (profile-csHMM) based RNA structural alignment
      algorithm. Experiments indicate that the proposed method can make the alignment
      speed up to 11 times faster without degrading the accuracy of the RNA alignment.

PMID- 19390683
TI  - Common gene variants in the tumor necrosis factor (TNF) and TNF receptor
      superfamilies and NF-kB transcription factors and non-Hodgkin lymphoma risk.
AB  - BACKGROUND: A promoter polymorphism in the pro-inflammatory cytokine tumor
      necrosis factor (TNF) (TNF G-308A) is associated with increased non-Hodgkin
      lymphoma (NHL) risk. The protein product, TNF-alpha, activates the nuclear factor
      kappa beta (NF-kappaB) transcription factor, and is critical for inflammatory and
      apoptotic responses in cancer progression. We hypothesized that the TNF and NF
      kappaB pathways are important for NHL and that gene variations across the
      pathways may alter NHL risk. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 500 tag
      single nucleotide polymorphisms (SNPs) from 48 candidate gene regions (defined as
      20 kb 5', 10 kb 3') in the TNF and TNF receptor superfamilies and the NF-kappaB
      and related transcription factors, in 1946 NHL cases and 1808 controls pooled
      from three independent population-based case-control studies. We obtained a gene
      region-level summary of association by computing the minimum p-value ("minP
      test"). We used logistic regression to compute odds ratios and 95% confidence
      intervals for NHL and four major NHL subtypes in relation to SNP genotypes and
      haplotypes. For NHL, the tail strength statistic supported an overall
      relationship between the TNF/NF-kappaB pathway and NHL (p = 0.02). We confirmed
      the association between TNF/LTA on chromosome 6p21.3 with NHL and found the LTA
      rs2844484 SNP most significantly and specifically associated with the major
      subtype, diffuse large B-cell lymphoma (DLBCL) (p-trend = 0.001). We also
      implicated for the first time, variants in NFKBIL1 on chromosome 6p21.3,
      associated with NHL. Other gene regions identified as statistically significantly
      associated with NHL included FAS, IRF4, TNFSF13B, TANK, TNFSF7 and TNFRSF13C.
      Accordingly, the single most significant SNPs associated with NHL were FAS
      rs4934436 (p-trend = 0.0024), IRF4 rs12211228 (p-trend = 0.0026), TNFSF13B
      rs2582869 (p-trend = 0.0055), TANK rs1921310 (p-trend = 0.0025), TNFSF7
      rs16994592 (p-trend = 0.0024), and TNFRSF13C rs6002551 (p-trend = 0.0074). All
      associations were consistent in each study with no apparent specificity for NHL
      subtype. CONCLUSIONS/SIGNIFICANCE: Our results provide consistent evidence that
      variation in the TNF superfamily of genes and specifically within chromosome
      6p21.3 impacts lymphomagenesis. Further characterization of these susceptibility
      loci and identification of functional variants are warranted.

PMID- 19390685
TI  - Non-invasive imaging of acute renal allograft rejection in rats using small
      animal F-FDG-PET.
AB  - BACKGROUND: At present, renal grafts are the most common solid organ transplants
      world-wide. Given the importance of renal transplantation and the limitation of
      available donor kidneys, detailed analysis of factors that affect transplant
      survival are important. Despite the introduction of new and effective
      immunosuppressive drugs, acute cellular graft rejection (AR) is still a major
      risk for graft survival. Nowadays, AR can only be definitively by renal biopsy.
      However, biopsies carry a risk of renal transplant injury and loss. Most
      important, they can not be performed in patients taking anticoagulant drugs.
      METHODOLOGY/PRINCIPAL FINDINGS: We present a non-invasive, entirely image-based
      method to assess AR in an allogeneic rat renal transplantation model using small
      animal positron emission tomography (PET) and (18)F-fluorodeoxyglucose (FDG). 3 h
      after i.v. injection of 30 MBq FDG into adult uni-nephrectomized, allogeneically
      transplanted rats, tissue radioactivity of renal parenchyma was assessed in vivo
      by a small animal PET-scanner (post operative day (POD) 1,2,4, and 7) and post
      mortem dissection. The mean radioactivity (cps/mm(3) tissue) as well as the
      percent injected dose (%ID) was compared between graft and native reference
      kidney. Results were confirmed by histological and autoradiographic analysis.
      Healthy rats, rats with acute CSA nephrotoxicity, with acute tubular necrosis,
      and syngeneically transplanted rats served as controls. FDG-uptake was
      significantly elevated only in allogeneic grafts from POD 1 on when compared to
      the native kidney (%ID graft POD 1: 0.54+/-0.06; POD 2: 0.58+/-0.12; POD 4:
      0.81+/-0.06; POD 7: 0.77+/-0.1; CTR: 0.22+/-0.01, n = 3-28). Renal FDG-uptake in
      vivo correlated with the results obtained by micro-autoradiography and the degree
      of inflammatory infiltrates observed in histology. CONCLUSIONS/SIGNIFICANCE: We
      propose that graft FDG-PET imaging is a new option to non-invasively,
      specifically, early detect, and follow-up acute renal rejection. This method is
      potentially useful to improve post-transplant rejection monitoring.

PMID- 19390686
TI  - Episodic evolution and adaptation of chloroplast genomes in ancestral grasses.
AB  - BACKGROUND: It has been suggested that the chloroplast genomes of the grass
      family, Poaceae, have undergone an elevated evolutionary rate compared to most
      other angiosperms, yet the details of this phenomenon have remained obscure. To
      know how the rate change occurred during evolution, estimation of the time-scale
      with reliable calibrations is needed. The recent finding of 65 Ma grass
      phytoliths in Cretaceous dinosaur coprolites places the diversification of the
      grasses to the Cretaceous period, and provides a reliable calibration in studying
      the tempo and mode of grass chloroplast evolution. METHODOLOGY/PRINCIPAL
      FINDINGS: By using chloroplast genome data from angiosperms and by taking account
      of new paleontological evidence, we now show that episodic rate acceleration both
      in terms of non-synonymous and synonymous substitutions occurred in the common
      ancestral branch of the core Poaceae (a group formed by rice, wheat, maize, and
      their allies) accompanied by adaptive evolution in several chloroplast proteins,
      while the rate reverted to the slow rate typical of most monocot species in the
      terminal branches. CONCLUSIONS/SIGNIFICANCE: Our finding of episodic rate
      acceleration in the ancestral grasses accompanied by adaptive molecular evolution
      has a profound bearing on the evolution of grasses, which form a highly
      successful group of plants. The widely used model for estimating divergence times
      was based on the assumption of correlated rates between ancestral and descendant
      lineages. However, the assumption is proved to be inadequate in approximating the
      episodic rate acceleration in the ancestral grasses, and the assumption of
      independent rates is more appropriate. This finding has implications for studies
      of molecular evolutionary rates and time-scale of evolution in other groups of
      organisms.

PMID- 19390687
TI  - Screening for C3 deficiency in newborns using microarrays.
AB  - BACKGROUND: Dried blood spot samples (DBSS) from newborns are widely used in
      neonatal screening for selected metabolic diseases and diagnostic possibilities
      for additional disorders are continuously being evaluated. Primary
      immunodeficiency disorders comprise a group of more than one hundred diseases,
      several of which are fatal early in life. Yet, a majority of the patients are not
      diagnosed due to lack of high-throughput screening methods. METHODOLOGY/PRINCIPAL
      FINDINGS: We have previously developed a system using reverse phase protein
      microarrays for analysis of IgA levels in serum samples. In this study, we
      extended the applicability of the method to include determination of complement
      component C3 levels in eluates from DBSS collected at birth. Normal levels of C3
      were readily detected in 269 DBSS from healthy newborns, while no C3 was detected
      in sera and DBSS from C3 deficient patients. CONCLUSIONS/SIGNIFICANCE: The
      findings suggest that patients with deficiencies of specific serum proteins can
      be identified by analysis of DBSS using reverse phase protein microarrays.

PMID- 19390688
TI  - Innervation of gonadotropin-releasing hormone neurons by peptidergic neurons
      conveying circadian or energy balance information in the mouse.
AB  - BACKGROUND: Secretion of gonadotropin-releasing hormone (GnRH) produced in
      neurons in the basal forebrain is the primary regulator of reproductive
      maturation and function in mammals. Peptidergic signals relating to circadian
      timing and energy balance are an important influence on the reproductive axis.
      The aim of this study was to investigate the innervation of GnRH neurons by
      peptidergic neurons. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemistry and
      confocal microscopy were used to detect appositions of peptidergic fibers (NPY,
      beta-endorphin, MCH) associated with energy balance and metabolic status in
      transgenic mice expressing a green fluorescent protein reporter construct in GnRH
      neurons. The frequency of these appositions was compared to those of vasoactive
      intestinal peptide (VIP), a hypothalamic neuropeptide likely to convey circadian
      timing information to the GnRH secretory system. The majority of GnRH neurons (73
      87%) were closely apposed by fibers expressing NPY, beta-endorphin, or MCH, and a
      significant proportion of GnRH neurons (28%) also had close contacts with VIP-ir
      fibers. CONCLUSIONS/SIGNIFICANCE: It is concluded that GnRH neurons in the mouse
      receive a high frequency of direct modulatory inputs from multiple hypothalamic
      peptide systems known to be important in conveying circadian information and
      signalling energy balance.

PMID- 19390689
TI  - A partial structural and functional rescue of a retinitis pigmentosa model with
      compacted DNA nanoparticles.
AB  - Previously we have shown that compacted DNA nanoparticles can drive high levels
      of transgene expression after subretinal injection in the mouse eye. Here we
      delivered compacted DNA nanoparticles containing a therapeutic gene to the
      retinas of a mouse model of retinitis pigmentosa. Nanoparticles containing the
      wild-type retinal degeneration slow (Rds) gene were injected into the subretinal
      space of rds(+/-) mice on postnatal day 5. Gene expression was sustained for up
      to four months at levels up to four times higher than in controls injected with
      saline or naked DNA. The nanoparticles were taken up into virtually all
      photoreceptors and mediated significant structural and biochemical rescue of the
      disease without histological or functional evidence of toxicity.
      Electroretinogram recordings showed that nanoparticle-mediated gene transfer
      restored cone function to a near-normal level in contrast to transfer of naked
      plasmid DNA. Rod function was also improved. These findings demonstrate that
      compacted DNA nanoparticles represent a viable option for development of gene
      based interventions for ocular diseases and obviate major barriers commonly
      encountered with non-viral based therapies.

PMID- 19390690
TI  - Validation of 2006 WHO prediction scores for true HIV infection in children less
      than 18 months with a positive serological HIV test.
AB  - INTRODUCTION: All infants born to HIV-positive mothers have maternal HIV
      antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction
      (PCR) is not available, August 2006 World Health Organization (WHO)
      recommendations suggest that clinical criteria may be used for starting
      antiretroviral treatment (ART) in HIV seropositive children <18 months.
      Predictors are at least two out of sepsis, severe pneumonia and thrush, or any
      stage 4 defining clinical finding according to the WHO staging system. METHODS
      AND RESULTS: From January 2005 to October 2006, we conducted a prospective study
      on 236 hospitalized children <18 months old with a positive HIV serological test
      at the national reference hospital in Kigali. The following data were collected:
      PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were
      present in 148 of 236 children (62.7%) and in 95 of 124 infected children,
      resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%),
      clinical diagnosis was made based on severe unexplained malnutrition (stage 4
      clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4
      count had a sensitivity of 55.6% and a specificity of 78.5%. CONCLUSION: As PCR
      is not yet widely available, clinical diagnosis is often necessary, but these
      criteria have poor specificity and therefore have limited use for HIV diagnosis.
      Unexplained malnutrition is not clearly enough defined in WHO recommendations.
      Extra pulmonary tuberculosis (TB), almost impossible to prove in young children,
      may often be the cause of malnutrition, especially in HIV-affected families more
      often exposed to TB. Food supplementation and TB treatment should be initiated
      before starting ART in children who are staged based only on severe malnutrition.

PMID- 19390691
TI  - Synergetic effects of granulocyte-colony stimulating factor and cognitive
      training on spatial learning and survival of newborn hippocampal neurons.
AB  - Granulocyte-Colony Stimulating Factor (G-CSF) is an endogenous hematopoietic
      growth factor known for its role in the proliferation and differentiation of
      cells of the myeloic lineage. Only recently its significance in the CNS has been
      uncovered. G-CSF attenuates apoptosis and controls proliferation and
      differentiation of neural stem cells. G-CSF activates upstream kinases of the
      cAMP response element binding protein (CREB), which is thought to facilitate the
      survival of neuronal precursors and to recruit new neurons into the dentate
      gyrus. CREB is also essential for spatial long-term memory formation. To assess
      the role and the potential of this factor on learning and memory-formation we
      systemically administered G-CSF in rats engaged in spatial learning in an eight
      arm radial maze. G-CSF significantly improved spatial learning and increased in
      combination with cognitive training the survival of newborn neurons in the
      hippocampus as measured by bromodeoxyuridine and doublecortin
      immunohistochemistry. Additionally, G-CSF improved re-acquisition of spatial
      information after 26 days. These findings support the hypothesis that G-CSF can
      enhance learning and memory formation. Due to its easy applicability and its
      history as a well-tolerated hematological drug, the use of G-CSF opens up new
      neurological treatment opportunities in conditions where learning and memory
      formation deficits occur.

PMID- 19390692
TI  - Changes in retinal pigment epithelium related to cigarette smoke: possible
      relevance to smoking as a risk factor for age-related macular degeneration.
AB  - Age-related Macular Degeneration (AMD) is a major cause of central vision loss in
      the elderly and smoking is a primary risk factor associated with the prevalence
      and incidence of AMD. To better understand the cellular and molecular bases for
      the association between smoking and AMD, we determined the effects of
      Benzo(a)Pyrene (B(a)P), a toxic element in cigarette smoke, on cultured retinal
      pigment epithelia (RPE) and we examined the RPE/choroid from mice exposed to
      chronic cigarette smoke. We measured: mitochondrial DNA (mtDNA) damage,
      phagocytic activity, lysosomal enzymes, exosome markers and selected complement
      pathway components. In the presence of a non-cytotoxic dose of B(a)P, there was
      extensive mtDNA damage but no nuclear DNA damage. RPE phagocytic activity was not
      altered but there were increased lysosomal activity, exocytotic activity and
      complement pathway components. Retinas from mice exposed to cigarette smoke
      contained markers for mtDNA damage, exosomes and complement pathway components
      surrounding Bruch's membrane. Markers for these processes are found in drusen
      from AMD patients. Thus, smoking may cause damage to mtDNA and increased
      degradative processes in the RPE. These altered cell biological processes in the
      RPE may contribute to the formation of drusen in individuals who are cigarette
      smokers and underlie susceptibility to genetic mutations associated with AMD.

PMID- 19390693
TI  - SVOP is a nucleotide binding protein.
AB  - BACKGROUND: Synaptic Vesicle Protein 2 (SV2) and SV2-related protein (SVOP) are
      transporter-like proteins that localize to neurotransmitter-containing vesicles.
      Both proteins share structural similarity with the major facilitator (MF) family
      of small molecule transporters. We recently reported that SV2 binds nucleotides,
      a feature that has also been reported for another MF family member, the human
      glucose transporter 1 (Glut1). In the case of Glut1, nucleotide binding affects
      transport activity. In this study, we determined if SVOP also binds nucleotides
      and assessed its nucleotide binding properties. METHODOLOGY/PRINCIPAL FINDINGS:
      We performed in vitro photoaffinity labeling experiments with the photoreactive
      ATP analogue, 8-azido-ATP[gamma] biotin and purified recombinant SVOP-FLAG fusion
      protein. We found that SVOP is a nucleotide-binding protein, although both its
      substrate specificity and binding site differ from that of SV2. Within the
      nucleotides tested, ATP, GTP and NAD show same level of inhibition on SVOP-FLAG
      labeling. Dose dependent studies indicated that SVOP demonstrates the highest
      affinity for NAD, in contrast to SV2, which binds both NAD and ATP with equal
      affinity. Mapping of the binding site revealed a single region spanning
      transmembrane domains 9-12, which contrasts to the two binding sites in the large
      cytoplasmic domains in SV2A. CONCLUSIONS/SIGNIFICANCE: SVOP is the third MF
      family member to be found to bind nucleotides. Given that the binding sites are
      unique in SVOP, SV2 and Glut1, this feature appears to have arisen separately.

PMID- 19390694
TI  - A Nest of LTR Retrotransposons Adjacent the Disease Resistance-Priming Gene NPR1
      in Beta vulgaris L. U.S. Hybrid H20.
AB  - A nest of long terminal repeat (LTR) retrotransposons (RTRs), discovered by
      LTR_STRUC analysis, is near core genes encoding the NPR1 disease resistance
      activating factor and a heat-shock-factor-(HSF-) like protein in sugarbeet hybrid
      US H20. SCHULTE, a 10 833 bp LTR retrotransposon, with 1372 bp LTRs that are 0.7%
      divergent, has two ORFs with unexpected introns but encoding a reverse
      transcriptase with rve and Rvt2 domains similar to Ty1/copia-type
      retrotransposons and a hypothetical protein. SCHULTE produced significant
      nucleotide BLAST alignments with repeat DNA elements from all four families of
      plants represented in the TIGR plant repeat database (PRD); the best nucleotide
      sequence alignment was to ToRTL1 in Lycopersicon esculentum. A second sugarbeet
      LTR retrotransposon, SCHMIDT, 11 565 bp in length, has 2561 bp LTRs that share
      100% identity with each other and share 98-99% nucleotide sequence identity over
      10% of their length with DRVs, a family of highly repetitive, relatively small
      DNA sequences that are widely dispersed over the sugarbeet genome. SCHMIDT
      encodes a complete gypsy-like polyprotein in a single ORF. Analysis using
      LTR_STRUC of an in silico deletion of both of the above two LTR retrotransposons
      found that SCHULTE and SCHMIDT had inserted within an older LTR retrotransposon,
      resulting in a nest that is only about 10 Kb upstream of NPR1 in sugarbeet hybrid
      US H20.

PMID- 19390695
TI  - Production of antibodies against multipass membrane proteins expressed in human
      tumor cells using dendritic cell immunization.
AB  - Antibody mediated therapeutic strategies against human malignant tumors have been
      widely authorized and clinically applied to cancer patients. In order to develop
      methods to generate antibodies reactive to the extracellular domains of multipass
      plasma membrane proteins specifically expressed in malignant tumors, we examined
      the use of dendritic cells (DCs) for immunization. DCs were transduced with genes
      encoding the human six transmembrane epithelial antigen of prostate 1 (STEAP1),
      STEAP4, and seven transmembrane prostate specific G-protein coupled receptor
      (PSGR). Mice were immunized with these DCs and followed by repeated booster
      immunization with plasmids expressing each protein. The immunized mice produced
      significant amounts of antibodies against these proteins. Our results suggest
      that DC immunization is an effective method to produce antibodies reactive to
      extracellular regions of plasma membrane proteins with multiple-transmembrane
      domains, and may be useful to develop antibody mediated antitumor therapies.

PMID- 19390696
TI  - Sequence-based prediction of type III secreted proteins.
AB  - The type III secretion system (TTSS) is a key mechanism for host cell interaction
      used by a variety of bacterial pathogens and symbionts of plants and animals
      including humans. The TTSS represents a molecular syringe with which the bacteria
      deliver effector proteins directly into the host cell cytosol. Despite the
      importance of the TTSS for bacterial pathogenesis, recognition and targeting of
      type III secreted proteins has up until now been poorly understood. Several
      hypotheses are discussed, including an mRNA-based signal, a chaperon-mediated
      process, or an N-terminal signal peptide. In this study, we systematically
      analyzed the amino acid composition and secondary structure of N-termini of 100
      experimentally verified effector proteins. Based on this, we developed a machine
      learning approach for the prediction of TTSS effector proteins, taking into
      account N-terminal sequence features such as frequencies of amino acids, short
      peptides, or residues with certain physico-chemical properties. The resulting
      computational model revealed a strong type III secretion signal in the N-terminus
      that can be used to detect effectors with sensitivity of approximately 71% and
      selectivity of approximately 85%. This signal seems to be taxonomically universal
      and conserved among animal pathogens and plant symbionts, since we could
      successfully detect effector proteins if the respective group was excluded from
      training. The application of our prediction approach to 739 complete bacterial
      and archaeal genome sequences resulted in the identification of between 0% and
      12% putative TTSS effector proteins. Comparison of effector proteins with
      orthologs that are not secreted by the TTSS showed no clear pattern of signal
      acquisition by fusion, suggesting convergent evolutionary processes shaping the
      type III secretion signal. The newly developed program EffectiveT3
      (http://www.chlamydiaedb.org) is the first universal in silico prediction program
      for the identification of novel TTSS effectors. Our findings will facilitate
      further studies on and improve our understanding of type III secretion and its
      role in pathogen-host interactions.

PMID- 19390697
TI  - Rapid etiological classification of meningitis by NMR spectroscopy based on
      metabolite profiles and host response.
AB  - Bacterial meningitis is an acute disease with high mortality that is reduced by
      early treatment. Identification of the causative microorganism by culture is
      sensitive but slow. Large volumes of cerebrospinal fluid (CSF) are required to
      maximise sensitivity and establish a provisional diagnosis. We have utilised
      nuclear magnetic resonance (NMR) spectroscopy to rapidly characterise the
      biochemical profile of CSF from normal rats and animals with pneumococcal or
      cryptococcal meningitis. Use of a miniaturised capillary NMR system overcame
      limitations caused by small CSF volumes and low metabolite concentrations. The
      analysis of the complex NMR spectroscopic data by a supervised statistical
      classification strategy included major, minor and unidentified metabolites.
      Reproducible spectral profiles were generated within less than three minutes, and
      revealed differences in the relative amounts of glucose, lactate, citrate, amino
      acid residues, acetate and polyols in the three groups. Contributions from
      microbial metabolism and inflammatory cells were evident. The computerised
      statistical classification strategy is based on both major metabolites and minor,
      partially unidentified metabolites. This data analysis proved highly specific for
      diagnosis (100% specificity in the final validation set), provided those with
      visible blood contamination were excluded from analysis; 6-8% of samples were
      classified as indeterminate. This proof of principle study suggests that a rapid
      etiologic diagnosis of meningitis is possible without prior culture. The method
      can be fully automated and avoids delays due to processing and selective
      identification of specific pathogens that are inherent in DNA-based techniques.

PMID- 19390698
TI  - Lead bullet fragments in venison from rifle-killed deer: potential for human
      dietary exposure.
AB  - Human consumers of wildlife killed with lead ammunition may be exposed to health
      risks associated with lead ingestion. This hypothesis is based on published
      studies showing elevated blood lead concentrations in subsistence hunter
      populations, retention of ammunition residues in the tissues of hunter-killed
      animals, and systemic, cognitive, and behavioral disorders associated with human
      lead body burdens once considered safe. Our objective was to determine the
      incidence and bioavailability of lead bullet fragments in hunter-killed venison,
      a widely-eaten food among hunters and their families. We radiographed 30
      eviscerated carcasses of White-tailed Deer (Odocoileus virginianus) shot by
      hunters with standard lead-core, copper-jacketed bullets under normal hunting
      conditions. All carcasses showed metal fragments (geometric mean = 136 fragments,
      range = 15-409) and widespread fragment dispersion. We took each carcass to a
      separate meat processor and fluoroscopically scanned the resulting meat packages;
      fluoroscopy revealed metal fragments in the ground meat packages of 24 (80%) of
      the 30 deer; 32% of 234 ground meat packages contained at least one fragment.
      Fragments were identified as lead by ICP in 93% of 27 samples. Isotope ratios of
      lead in meat matched the ratios of bullets, and differed from background lead in
      bone. We fed fragment-containing venison to four pigs to test bioavailability;
      four controls received venison without fragments from the same deer. Mean blood
      lead concentrations in pigs peaked at 2.29 microg/dL (maximum 3.8 microg/dL) 2
      days following ingestion of fragment-containing venison, significantly higher
      than the 0.63 microg/dL averaged by controls. We conclude that people risk
      exposure to bioavailable lead from bullet fragments when they eat venison from
      deer killed with standard lead-based rifle bullets and processed under normal
      procedures. At risk in the U.S. are some ten million hunters, their families, and
      low-income beneficiaries of venison donations.

PMID- 19390699
TI  - Hypertrophic cardiomyopathy and tachyarrhythmias detected by a pacemaker.
AB  - A 56-year-old man came to the Pacemaker Clinic for his regular pacemaker control.
      He had experienced a syncopal episode in the previous week. He had a previous
      diagnosis of non-obstructive hypertrophic cardiomyopathy. Due to a previous
      syncope and documented 2:1 infrahisian block, a dual-chamber permanent pacemaker
      had been implanted a few years before. The device was interrogated, showing
      several ventricular high rate episodes. A careful analysis of the stored
      intracardiac electrograms showed ventricular tachycardia (VT) with 2:1
      ventriculoatrial conduction. The following presentation discusses the alternative
      diagnosis and clinical management in an unusual diagnosis of VT in the presence
      of non-obstructive hypertrophic cardiomyopathy.

PMID- 19390701
TI  - International exchange towards continuing education's and Brazilian cardiology's
      strengthening.

PMID- 19390700
TI  - Cardiogenic shock caused by disulfiram.
AB  - Drug intoxication with disulfiram is a rare condition that may lead to severe and
      potentially fatal cardiovascular manifestations such as cardiogenic shock. We
      report the case of a female patient with refractory shock after deliberate self
      poisoning with disulfiram. Clinical, biochemical and echocardiographic
      assessment, as well as invasive monitoring confirmed cardiogenic shock associated
      with this drug. The known mechanisms of action of disulfiram are discussed, and
      the major collateral effects, especially cardiovascular effects, are described.
      We underscore the importance of suspecting this diagnosis and of adopting prompt
      and the most adequate therapeutic approach in this context.

PMID- 19390702
TI  - The myocardium in tetralogy of Fallot: a histological and morphometric study.
AB  - BACKGROUND: Patients with Tetralogy of Fallot frequently develop ventricular
      dysfunction in the postoperative period. The histological basis of this
      functional alteration has been scarcely studied. OBJECTIVE: To evaluate
      myocardial remodeling in anatomical specimens, comparing the subepicardial and
      subendocardial regions, especially because the subendocardial region is easily
      approached by means of endomyocardial biopsy. METHODS: Transmural sections of
      myocardium from the right ventricular (RV) inflow tract, anterior wall and
      infundibulum, and from the left ventricular (LV) free wall were evaluated
      regarding the degree of cardiomyocyte hypertrophy, vascularization and
      interstitial fibrosis were analyzed. RESULTS: The mean diameter of subendocardial
      cardiomyocytes is similar to that of subepicardial cardiomyocytes in all regions,
      except for the RV infundibulum, in which subendocardial cardiomyocytes are
      significantly larger in relation to those of the subepicardium (p=0.007). The
      amount of interstitial collagen is in the upper limits of normal and was similar
      in the subendocardial layers in comparison with the subpericardial layer of each
      region; however, it was greater in the inflow tract and RV anterior wall than in
      the LV lateral wall. The numerical density of subendocardial capillaries was
      similar to that of the subepicardium and was lower than the mean minus two
      standard deviations of normal in all regions and layers, except for the
      infundibulum, in which the subepicardium showed normal values and the
      subendocardium showed values lower than the mean minus two standard deviations.
      CONCLUSION: The postnatal myocardial changes in Tetralogy of Fallot are
      homogeneously distributed in the subepicardial and subendocardial halves of the
      ventricular walls, except for the infundibulum, which has peculiar remodeling
      characteristics and, therefore, is not representative of the other ventricular
      regions and layers for morphometric studies.

PMID- 19390703
TI  - Renal and adrenal tumors with cardiac invasion: immediate surgical results in 14
      patients.
AB  - BACKGROUND: The resection of tumor thrombus of the inferior vena cava (IVC) and
      right atrium (RA) increases the survival rate of patients with renal/adrenal
      cancer. OBJECTIVE: To evaluate the surgical procedure in cases of IVC and RA in
      the treatment of renal and adrenal tumors. METHODS: Fourteen patients undergoing
      surgical intervention (during the period) between January 1997 and June 2007, for
      resection of IVC and/or RA thrombus due to renal or adrenal tumors, were
      retrospectively evaluated. The patients (64.2% male) presented with Wilms' tumor,
      clear cell carcinoma and adrenal adenocarcinoma, and had mean age of 4.5, 60.5
      and 2.5 years, respectively. Epidemiological characteristics and intra- and
      postoperative parameters were evaluated. RESULTS: Suprahepatic IVC tumor thrombus
      were observed in all the patients, and in 62.4% of them the thrombus invaded the
      RA. Thrombectomy was performed with extracorporeal circulation with deep
      hypothermia and total circulatory arrest in 85.7%, with mild hypothermia in the
      remaining cases. The inferior vena cava was ligated in 7.1% of the cases, and
      reconstruction with suture was performed in 92.9% of the patients. The duration
      of orotracheal intubation and length of hospital stay were different, according
      to the tumor type. Two deaths, due to intraoperative cardiorespiratory arrest,
      were seen among patients with adrenal adenocarcinoma. CONCLUSION: IVC and RA
      tumor thrombi are more frequent in patients with Wilms' tumor. More postoperative
      complications are seen in patients with adrenal adenocarcinoma, and the
      postoperative prognosis is better for patients with Wilms' tumor.

PMID- 19390704
TI  - Combination of amlodipine and enalapril in hypertensive patients with coronary
      disease.
AB  - BACKGROUND: Patients (pts) with stable coronary artery disease (CAD) can benefit
      from a decrease in the blood pressure (BP), according to recent studies.
      OBJECTIVE: To evaluate the efficacy and tolerability of the fixed combination:
      amlodipine + enalapril, when compared to amlodipine in the normalization of the
      diastolic arterial pressure (DAP) (<85 mmHg), in pts with CAD and systemic
      arterial hypertension (SAH). METHODS: Double-blind and randomized study, with two
      groups of pts with DAP > or =90 and <110 mmHg and CAD. Patients with left
      ventricular ejection fraction (LVEF) < 40%, symptoms of heart failure or angina
      class III and IV, severe diseases and DAP > or =110 mmHg during the four-week
      wash-out with atenolol treatment alone, were excluded. After the wash-out, pts
      were randomly distributed for the use of the combination (A) or amlodipine (B)
      and were followed every four weeks up to 98 days. The initial doses (in mg) were,
      respectively: A- 2.5/10 and B- 2.5; the doses were increased when DAP > 85mmHg,
      at the visits. Statistical analysis was carried out with chi2, Fischer and
      analysis of variance, for p< 0.05. RESULTS: Of the 110 selected pts, 72 (A= 32,
      B= 40) were randomized. The decreases in DAP and systolic arterial pressure (SAP)
      were significant (p< 0.01), but with no difference between the groups in mmHg:
      SAP, A (127.7 +/- 13.4) and B (125.3 +/- 12.6) (p= 0.45) and DAP, A (74.5 +/- 6.7
      mmHg) and B (75.5 +/- 6.7 mmHg) (p= 0.32). Group A presented a lower incidence of
      lower-limb edema: (7.1% vs 30.6%, p=0.02) on the 98th day of follow-up.
      CONCLUSION: The fixed combination of enalapril and amlodipine, as well as
      isolated amlodipine, was effective in the normalization of BP in pts with CAD and
      SAH stages I and II, adding blockage of the renin-angiotensin system.

PMID- 19390705
TI  - Cholesterol and fats in Brazilian foods: implications for prevention of
      atherosclerosis.
AB  - BACKGROUND: In order to perform food surveys and prescribe diets, food
      composition tables have to be consulted. However, these tables are limited to the
      description of fatty acids and cholesterol contents and do not provide
      information on the different preparation methods. OBJECTIVE: Based on data
      derived from an extensive analysis of the chemical composition of Brazilian
      foods, we assessed the impact of certain types of foods on diets recommended for
      the prevention of coronary disease. METHODS: The fatty acid and cholesterol
      composition of some types of foods and different preparation methods were
      analyzed. These results were used according to the recommendations of the
      American Heart Association for an 1,800 calorie diet. RESULTS: Cholesterol found
      in 100g of eggs (400mg) or fried beef liver (453mg) exceeds the amount
      recommended for secondary prevention, and there is no difference in cholesterol
      content between factory-farmed eggs and free-range eggs. The eggs had an average
      of 400mg of cholesterol per 100g, thus exceeding the recommended amount of up to
      300mg. Each egg has 50g on average; one egg can be consumed provided that not
      more than 100mg of cholesterol are consumed per day. As regards saturated fat,
      butter (55.2g), margarine (19.4g), tilsit cheese (20.4g), Brazilian Dutch Edam
      cheese (19.9g), yellow (16.8g) and fresh white cheese (15.5g) exceed the 14g
      recommended if 100g or more are consumed. The same is true for soy oil (17.5g)
      and corn oil (16.1g). CONCLUSION: Better knowledge on fat and cholesterol
      contents in foods allows the prescription of amounts not exceeding the
      recommended values for prevention, and this may result in better compliance to
      diets.

PMID- 19390706
TI  - Carotid artery structural and functional evaluation in relatives of type 2
      diabetic patients.
AB  - BACKGROUND: In Western countries type 2 diabetes mellitus (DM2) is the leading
      cause of morbidity and mortality, particularly from cardiovascular causes. Since
      a family history of diabetes, even in non-diabetic subjects, is regarded as an
      increased risk of coronary heart disease, the use of approved surrogate markers
      of early atherosclerosis, specially of ultrasonic measurements of the carotid
      arteries, is of vital importance. OBJECTIVE: To analyze the structural properties
      (intima-media thickness) and functional properties (distensibility measurement)
      of the carotid arteries in subjects with (FH+) a family history of type 2
      diabetes, in comparison to subjects without (FH-) a family history of type 2
      diabetes, both groups with no known cardiovascular risk factors. METHODS: 32
      individuals (male and female, age range, 21-47 years; 19 FH+, 13 FH-) had their
      right and left common and internal carotid arteries measured, using high
      resolution B-mode ultrasonography. Both groups had similar (p>0.05) age, BMI,
      blood pressure, and fasting blood glucose and insulin, leptin, and C-reactive
      protein (CRP) levels. RESULTS: The intima-media thickness (IMT) of the left
      common carotid artery (LCCA) in the FH+ group (0.568+/-0.107mm) was statistically
      greater (p=0.029) than in the FH- group (0.477+/-0.116mm). Multiple regression
      analysis identified age, overweight and obesity (determined by BMI), CRP, and LDL
      cholesterol levels as independent predictors of the IMT in the LCCA. CONCLUSION:
      FH+ individuals with no metabolic disorders presented greater IMT of the left
      common carotid artery (structural alteration) than FH- individuals, but normal
      vessel function.

PMID- 19390707
TI  - Prevalence and variables associated with physical inactivity in individuals with
      high and low socioeconomic status.
AB  - BACKGROUND: Studies that considered only the leisure physical activity found that
      the physical inactivity is higher among lower-income individuals. There is a
      possibility that this association shows modifications, when considering
      transportation, work and domestic activities. OBJECTIVE: To determine whether
      there is a difference between the prevalence of physical inactivity between
      individuals of high and low socioeconomic levels. METHODS: The sample consisted
      of individuals of both sexes, aged 18 or older, from two groups of different
      socioeconomic levels. The low socioeconomic level (LSEL) group consisted of the
      parents of students from a public school. The high socioeconomic level (HSEL)
      group consisted of the parents of students from a private College. The
      International Physical Activity Questionnaire (IPAQ) was used to determine the
      level of physical activity. RESULTS: A total of 91 individuals were evaluated in
      the LSEL group and 59 in the HSEL group. In the LSEL group, 42.9% (39) of the
      individuals were classified as insufficiently active, compared to 57.6% (34) of
      individuals in the HSEL group. Taking as a parameter of physical inactivity the
      time of weekly physical activity < 150 minutes, there was a decrease in the
      classification of inactivity in both groups, although with the maintenance of
      higher inactivity among individuals of HSEL (49.2% vs 28.6%; p= 0.01).
      CONCLUSION: The individuals of HSEL are more sedentary than the individuals of
      LSEL.

PMID- 19390708
TI  - Genetic factors in familial aggregation of blood pressure of Portuguese nuclear
      families.
AB  - BACKGROUND: Despite of the increase in the prevalence of hypertension in
      Portugal, the importance of genetic factors in blood pressure (BP) has not been
      studied extensively in our country. OBJECTIVES: To verify the indirect presence
      of vertical transmission of genetic factors between parents and children in BP
      values, and to estimate the magnitude of genetic factors contributing for
      variation in BP values in the population. METHODS: Sample size comprises 367
      individuals (164 parents and 203 children) pertaining the 107 nuclear families
      participating in 'Familias Activas' project, proceeding from different regions of
      North Portugal. The BP was measured with Omron model M6 (HEM-7001-E) digital
      device. SPSS 15.0 was used for data analysis; PEDSTATS was used to verify the
      structure of each family data. Familial correlations and heritability estimates
      were computed in FCOR and ASSOC modules of S.A.G.E. version 5.3. RESULTS: For
      systolic BP (SBP), correlation values were low to moderate (0.21< or = r < or
      =0.35); for diastolic BP (DBP) values were found to be moderate (0.24< or = r <
      or =0. 50). Genetic factors explain 43 and 49% of the total variation in SBP and
      DBP, respectively. CONCLUSION: A moderate amount of the SBP and the DBP is
      accounted for by genetic factors.

PMID- 19390709
TI  - Evaluation of baroreflex function in young spontaneously hypertensive rats.
AB  - BACKGROUND: The literature describes contradictory data regarding the onset of
      the baroreflex reduction in spontaneously hypertensive rats. OBJECTIVE: This
      investigation was undertaken to evaluate the baroreflex function in 13-week-old
      spontaneously hypertensive rats. METHODS: Male Wistar Kyoto (n=15) and
      spontaneously hypertensive rats (n=15) aged 13 weeks were studied. Cannulas were
      inserted in the abdominal aortic artery through the right femoral artery to
      measure mean arterial pressure and heart rate. Baroreflex function was calculated
      as the derivative of the variation of HR in function of the MAP variation (Delta
      heart rate/Delta mean arterial pressure) tested with a depressor dose of sodium
      nitroprusside (50microg/kg) and with a pressor dose of phenylephrine (8microg/kg)
      in the right femoral venous approach through an inserted cannula in awake
      spontaneously hypertensive rats and Wistar-Kyoto. Differences with p values <
      0.05 were considered statistically significant. RESULTS: Spontaneously
      hypertensive rats: Delta mean arterial pressure=43.5mmHg+/-5.2, Delta heart rate=
      59.7ppm+/-17.9 and Delta heart rate/Delta mean arterial pressure=1.3ppm/mmHg+/
      0.1 tested with phenylephrine; Wistar Kyoto: Delta mean arterial
      pressure=&56mmHg+/-3, Delta heart rate=*-114.9ppm+/-11.3 and Deltaheart
      rate/Delta mean arterial pressure=#1.9ppm/mmHg+/-0.3 tested with phenylephrine;
      spontaneously hypertensive rats: Delta mean arterial pressure=-45.6mmHg+/-8.1,
      Delta heart rate=40.1ppm+/-11.6 and Delta heart rate/Delta mean arterial
      pressure=0.9ppm/mmHg+/-0.5 tested with sodium nitroprusside; Wistar Kyoto: Delta
      mean arterial pressure=-39.8mmHg+/-6.2, Delta heart rate=51.9ppm+/-21.8 and Delta
      heart rate/Delta mean arterial pressure=1.4ppm/mmHg+/-0.7 tested with sodium
      nitroprusside (*p<0.05; #p<0.01; &<0.001). CONCLUSION: Our results showed that 13
      week-old spontaneously hypertensive rats presented reduced baroreflex function
      when tested with phenylephrine.

PMID- 19390710
TI  - Prognostic value of the collagen volume fraction in hypertrophic cardiomyopathy.
AB  - BACKGROUND: In hypertrophic cardiomyopathy (HCM), interstitial myocardial
      fibrosis is an important histological modification that has been associated with
      sudden death and evolution toward myocardial dilation. OBJECTIVE: To
      prospectively evaluate the prognostic value of the collagen volume fraction in
      HCM. METHODS: An endomyocardial biopsy of the right ventricle was successfully
      performed in 21 symptomatic patients with HCM. The myocardial collagen volume
      fraction (CVF) was determined by histology. The CVF was also determined in
      fragments of nine normal hearts from subjects deceased from non-cardiac causes.
      The patients were divided into above-median CVF and below-median CVF groups, and
      their clinical and echocardiographic characteristics and survival curves were
      compared. RESULTS: Among the patients, the CVF ranged from 1.86% to 29.9%, median
      6.19%; in normal hearts, from 0.13% to 1.46%, median 0.61% (p <0.0001 between HCM
      and control). There were no significant correlations between CVF and baseline
      echocardiographic measures. Patients with CVF < or =6.19% and CVF> 6.19% were
      compared and no baseline differences were observed. However, after an average
      follow-up period of 110 months, four deaths occurred (two sudden, two due to
      heart failure) in the group with increased CVF, whereas the patients of the group
      with lower CVF were all alive at the end of the period (p = 0.02). CONCLUSION:
      For the first time, myocardial fibrosis was prospectively associated with a worse
      prognosis in patients with HCM. Efforts should be directed to the quantification
      of myocardial fibrosis in HCM, on the premise that its association with the
      prognosis can aid in the stratification of risk for defibrillator implantation,
      and in the prescription of drugs that potentially promote myocardial repair.

PMID- 19390711
TI  - [B-type natriuretic peptide assessment in the diagnosis of rejection after
      pediatric heart transplant].
AB  - BACKGROUND: Rejection is one of the major causes of mortality following pediatric
      heart transplant. B-type natriuretic peptide (BNP) has been studied as a method
      for the diagnosis of acute rejection, especially in adult patients undergoing
      heart transplant. OBJECTIVE: To correlate serum BNP levels with acute rejection
      as diagnosed by endomyocardial biopsy in patients of the pediatric heart
      transplant group. METHODS: A total of 50 BNP samples were collected from 33
      children in the postoperative period of heart transplant, and data on age,
      gender, skin color, blood group, immune panel, follow-up time after transplant,
      functional class, immunosuppressive regimen used and number of rejections were
      analyzed. RESULTS: Thirty three children with median age of 10.13 years were
      analyzed; of these, 54% were females and 78% were Caucasians. BNP levels were
      determined at a mean time from transplant of 4.25 years. Nine episodes of
      rejection were diagnosed in eight patients (27%) by means of endomyocardial
      biopsy; of these, three were grade 3A, five were grade 2, and one had humoral
      rejection. At the moment of biopsy, most patients were asymptomatic. The mean
      serum BNP level was 77.18 pg/ml, with 144.22 pg/ml in the group with rejection
      and 62.46 pg/ml in the group without rejection, with p = 0.02. CONCLUSION:
      Asymptomatic children can present acute rejection in the postoperative period of
      heart transplant. Serum BNP levels show a statistically significant difference in
      the group with rejection and thus can be an additional method in the diagnosis of
      cardiac rejection.

PMID- 19390712
TI  - Inflammatory markers of cardiovascular disease in the elderly.
AB  - Most information on the role of inflammatory markers as cardiovascular disease
      predictors concerns only middle-aged individuals. This review aims at evaluating
      the role of inflammatory markers as cardiovascular disease predictors in the
      elderly. The Medline (Pubmed) and Cochrane databases were used in the search,
      using the key words. After adding the following filters: LIMITS: Aged 65+ years,
      Humans, Randomized Controlled Trial, Meta-Analysis, Review, Clinical Trials, 554
      studies were identified. Of these, 120 were selected and evaluated regarding
      their power of evidence (classification of the Oxford Centre for Evidence-Based
      Medicine). In studies with patients older than 65 years, interleukin 6 (IL-6),
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) showed to be
      good predictors of cardiovascular events. Regarding C-reactive protein (CRP), the
      data are inconsistent, as it appears to have lower power of prediction in the
      elderly when compared to middle-aged individuals. Fibrinogen levels seem to be
      predictors of mortality, although they are non-specific predictors, i.e., not
      solely of cardiovascular mortality. Additionally, the inflammatory markers are
      also indicative of functional decline and mortality, regardless of the presence
      of cardiovascular disease. The current evidence is not sufficient to allow the
      routine use of inflammatory markers in the elderly, as there are few studies in
      this age range and most of them are short-term ones with a small number of
      inflammatory markers. The routine request for these markers must be decided on an
      individual basis.

PMID- 19390713
TI  - Systematic review and meta-analysis of diagnostic and prognostic studies: a
      tutorial.
AB  - Systematic reviews with meta-analysis of studies on diagnostic tests or
      prognostic factors are research tools that are still being developed. The
      objective of the present paper is to describe the methodology of systematic
      review and meta-analysis of this type of studies, step by step. A literature
      review on the subject was made, the recommendations were compiled and the paper
      was organized in: a) Introduction, b) Details on the eight steps to be followed,
      c) Form of publication of a systematic review with meta-analysis, and d)
      Conclusion. The systematic review methods were thoroughly described with a
      critical analysis of the methods of statistical compilation of results, with
      emphasis on the utilization of the Summary Receiver Operator Characteristic
      curve. References for the details of each statistical technique used were
      provided in the meta-analysis. We concluded that systematic reviews with meta
      analysis of diagnostic tests or prognostic factors are useful in data compilation
      of various studies on the same subject, since they reduce biases and increase the
      statistical power of the primary research.

PMID- 19390714
TI  - Case 3/2009--six-month-old infant with large interventricular communication and
      enlarged thymus, which simulated the characteristic image of total anomalous
      drainage of the pulmonary veins at the chest x-ray.

PMID- 19390715
TI  - Smoking and asthma control.

PMID- 19390716
TI  - Evaluation of criteria for the diagnosis of asthma using an epidemiological
      questionnaire.
AB  - OBJECTIVE: To evaluate criteria for the diagnosis of asthma in an epidemiological
      survey. METHODS: Adolescents (13-14 years of age) and legal guardians of
      schoolchildren (6-7 years of age) in the city of Santo Andre, Brazil, completed
      the International Study of Asthma and Allergies in Childhood (ISAAC) standard
      written questionnaire. Affirmative responses regarding wheezing within the last
      12 months, asthma ever, bronchitis ever (question added at the end of the
      questionnaire), as well as the overall ISAAC score above the predefined cutoff
      points, were considered indicative of asthma. RESULTS: The legal guardians of
      2,180 schoolchildren and 3,231 adolescents completed the questionnaires properly.
      Depending on the criterion adopted, the prevalence of asthma ranged from 4.9% to
      26.8% for the schoolchildren and from 8.9% to 27.9% for the adolescents. The
      criteria with the lowest and highest prevalences were, respectively, physician
      diagnosed asthma and physician-diagnosed bronchitis. When compared with other
      criteria, physician-diagnosed bronchitis showed concordance levels between 71.9%
      and 79.4%, positive predictive values between 0.16 and 0.63 and poor concordance
      (kappa: 0.21-0.46). Strong concordance levels were found only between wheezing
      within the last 12 months and the overall ISAAC score (kappa: 0.82 and 0.98).
      CONCLUSIONS: The prevalence of asthma varied significantly, depending on the
      criterion adopted, and there was poor concordance among the criteria. Wheezing
      within the last 12 months and the overall ISAAC score are the best criteria for
      the diagnosis of asthma, whereas the question regarding bronchitis ever did not
      improve the questionnaire. Modifications in this instrument can make it difficult
      to draw comparisons and should therefore be carefully evaluated.

PMID- 19390717
TI  - Incidence of asthma symptoms and decreased pulmonary function in young amateur
      swimmers.
AB  - OBJECTIVE: To investigate the incidence of asthma symptoms in young amateur
      swimmers, and to describe the clinical treatment of the children with asthma in a
      private sports club in the city of Sao Paulo, Brazil. METHODS: The study included
      171 amateur swimmers, ranging from 6 to14 years of age. All of the participants
      or their legal guardians were asked to complete the International Study of Asthma
      and Allergies in Childhood (ISAAC) questionnaire, and 119 were submitted to
      pulmonary function testing at rest. RESULTS: The overall incidence of asthma
      symptoms (ISAAC score > 6) among the swimmers was 16.8%. Of the 119 swimmers
      submitted to spirometry, 39 (32.7%) presented spirometric alterations (FEV1/FVC <
      0.75). Among those with an ISAAC score > 6, there were 10 (31.2%) who stated that
      they were receiving no asthma treatment. Of those who reported receiving
      pharmacological treatment, 24% made use of bronchodilators but not of
      corticosteroids. CONCLUSIONS: The incidence of asthma symptoms and pulmonary
      function alterations among amateur swimmers within the 6-14 age bracket was high.
      In addition, a relevant proportion of these athletes were receiving no treatment.

PMID- 19390718
TI  - Compensatory sweating after thoracoscopic sympathectomy: characteristics,
      prevalence and influence on patient satisfaction.
AB  - OBJECTIVE: This prospective study aimed at investigating predictive factors for
      compensatory sweating after thoracoscopic sympathectomy. METHODS: From 2000 to
      2002, 80 patients (53 females and 27 males) underwent thoracoscopic sympathectomy
      to treat hyperhidrosis. Patient ages ranged from 12 to 56 years, and the mean
      post-operative follow-up period was 42.51 +/- 5.98 months. Patient satisfaction
      with the results was evaluated through the use of a rating scale. The procedure
      was performed bilaterally: at the T2 level for facial hyperhidrosis; at the T3-T4
      level for axillary hyperhidrosis; and at the T3 level for palmar hyperhidrosis.
      RESULTS: Post-operatively, 68 patients (85.0%) presented compensatory sweating,
      which was classified as mild in 23 (33.8%), moderate in 23 (33.8%) and severe in
      22 (32.4%). Considering the final surgical results, 70 patients (87.5%) were
      satisfied with the outcome of the operation, whereas 10 patients (12.5%) were
      dissatisfied. The level of patient satisfaction varied according to gender, age,
      body mass index (BMI) and extent of denervation. The compensatory sweating was
      more severe on the abdomen and back than on the legs. CONCLUSIONS: Although
      compensatory sweating, which is a common adverse effect of sympathectomy,
      occurred in the majority of cases, the level of patient satisfaction was high.
      The best candidates for thoracoscopic sympathectomy are young adult women with a
      BMI < 24.9 kg/m(2).

PMID- 19390719
TI  - Prevalence of pectus carinatum and pectus excavatum in students in the city of
      Manaus, Brazil.
AB  - OBJECTIVE: To determine the prevalence of congenital anterior chest wall
      deformities in 11- to 14-year-old students. METHODS: Students participating in
      the study were recruited from public schools in the city of Manaus, Brazil. The
      statistically significant sample (precision, 1%; 95% CI) comprised 1,332
      students. Pectus deformities were identified by physical examination of the
      chest, and the individuals with one of these deformities completed a
      questionnaire regarding heredity and symptoms resulting from the chest
      abnormality. RESULTS: The mean age of the participants was 11.7 years. The
      prevalence of pectus abnormalities was 1.95% (pectus excavatum: 1.275%; pectus
      carinatum: 0.675%). Of the 26 students with a pectus deformity, 17 (65.4%) had
      pectus excavatum, and 18 (69.2%) were male. Concomitant scoliosis was observed in
      3 cases (11.5%). A family history of pectus was reported by 17 students (65.4%),
      and 17 (65.4%) reported chest pain, dyspnea or palpitations. CONCLUSIONS: In this
      study, the prevalence of pectus deformities (1.95%) was lower than that reported
      in other studies conducted in Brazil (3.6-4.9%) but was higher than that reported
      in the literature (mean, 1%).

PMID- 19390720
TI  - Postintubation injuries and open surgical tracheostomy: should we always perform
      isthmectomy?
AB  - OBJECTIVE: To evaluate the influence of the surgical team (general surgery or
      thoracic surgery) and the surgical technique (with or without isthmectomy) on the
      incidence of postintubation injuries in the airways of tracheostomized patients.
      METHODS: Between January 1st and August 31st, 2007, 164 patients admitted to the
      adult intensive care unit and tracheally intubated for more than 24 h were
      studied prospectively at the Sumare State Hospital, located at the city of
      Sumare, Brazil. When tracheostomy was necessary, these patients were randomly
      assigned to thoracic or general surgery teams. All of the patients were submitted
      to fiberoptic tracheoscopy for decannulation or late evaluation of the airway.
      RESULTS: Of the 164 patients in the study, 90 (54.88%) died (due to causes
      unrelated to the procedure), 67 (40.85%) completed follow-up, and 7 (4.27%) were
      lost to follow-up. Of the 67 patients who completed follow-up, 32 had undergone
      tracheostomy (21 by the general surgery team and 11 by the thoracic surgery
      team), and 22 had been submitted to isthmectomy (11 by the general surgery team
      and 11 by the thoracic surgery team). There was no difference between the
      surgical teams in terms of the incidence of stomal complications. However, there
      was a significant difference when the surgical techniques (with or without
      isthmectomy) were compared. CONCLUSIONS: Not performing isthmectomy in parallel
      with tracheostomy leads the surgeon to open the tracheal stoma more distally than
      expected. In such cases, there were more stomal complications.

PMID- 19390721
TI  - Video-assisted thoracoscopy for the diagnosis of diffuse parenchymal lung
      disease.
AB  - OBJECTIVE: To evaluate the role of video-assisted thoracoscopy in the diagnosis
      of diffuse parenchymal lung diseases. METHODS: The medical charts of patients
      suspected of having diffuse parenchymal lung disease were retrospectively
      reviewed, as were the results of the anatomopathological examination of lung
      biopsy specimens collected through video-assisted thoracoscopy. RESULTS: Of the
      48 patients included in the study, 25 (52.08%) were female and 23 (47.92%) were
      male. The mean age was 58.77 years (range, 20-76 years). A total of 54 biopsy
      fragments were submitted to anatomopathological examination: 24 (44.44%) from the
      lingula; 10 (18.52%) from the left lower lobe; 7 (12.96%) from the right middle
      lobe; 6 (11.11%) from the right lower lobe; 5 (9.26%) from the left upper lobe;
      and 2 (3.71%) from the right upper lobe. The mean duration of thoracic drainage
      was 2.2 days. Adverse events included conversion to thoracotomy, in 2 patients
      (4.17%), and residual pneumothorax, in 1 (2.08%). The definitive diagnosis was
      made in 46 patients (95.83%), and idiopathic interstitial pneumonia was the
      predominant diagnosis (in 54.18%). The most common diagnoses were usual
      interstitial pneumonia (in 29.27%), nonspecific interstitial pneumonia (in
      16.67%) and hypersensitivity pneumonia (in 12.50%). CONCLUSIONS: Lung biopsy
      through video-assisted thoracoscopy is a safe, effective and viable procedure for
      the diagnosis of diffuse parenchymal lung diseases.

PMID- 19390722
TI  - Nutritional profile of lung transplant candidates.
AB  - OBJECTIVE: To determine the nutritional profile of lung transplant candidates.
      METHODS: A retrospective cross-sectional study involving lung transplant
      candidates at a public hospital in the city of Sao Paulo, Brazil. Data related to
      gender, age and underlying lung disease were compiled for the participants. For
      the assessment of the nutritional profile of the patients, body mass index (BMI),
      mid-arm muscle circumference (MAMC), waist circumference and triceps skinfold
      thickness (TST) were determined during the first outpatient visit. RESULTS: We
      included 117 patients, 69 of which (59%) were male. The mean age of the
      participants was 42.5 +/- 15.2 years. The most prevalent underlying disease, seen
      in 29 patients (24.8%), was pulmonary emphysema. The nutritional profile was
      considered normal in 48.3% of the patients with pulmonary emphysema, 55% of those
      with cystic fibrosis, 56% of those with bronchiectasis and 50% of those with
      other lung diseases. The majority (51.7%) of the patients with pulmonary fibrosis
      were classified as overweight. The TSTs indicated that the risk of depletion was
      highest (64.7%) among the patients with cystic fibrosis, followed by those with
      bronchiectasis (52.6%). CONCLUSIONS: Patients with pulmonary fibrosis presented
      the highest BMIs, although the corresponding TSTs and MAMCs were normal. Patients
      with cystic fibrosis and bronchiectasis presented the highest prevalence of
      nutritional depletion, based on TST and MAMC.

PMID- 19390723
TI  - Correlation between clinical parameters and health-related quality of life in
      women with COPD.
AB  - OBJECTIVE: To correlate health-related quality of life (HRQL) of women with COPD
      with clinical parameters and with the six-minute walk distance (6MWD; six-minute
      walk test). METHODS: Cross-sectional study involving 30 female patients diagnosed
      with mild or moderate COPD treated at the Respiratory Outpatient Clinic of the
      Presidente Dutra University Hospital. Patients completed the Saint George's
      Respiratory Questionnaire (SGRQ) and were evaluated in terms of respiratory
      pressures, spirometry parameters and 6MWD. Descriptive statistical analysis was
      carried out, as were Student's t-tests for dependent variables, together with
      Pearson's and Spearman's correlation coefficients for numerical and ordinal
      variables, respectively. RESULTS: According to the SGRQ total scores, HRQL was
      impaired, to some extent, in most of the participants. Most SGRQ total scores
      were between the second and the third quartiles, reflecting poor HRQL. The
      participants also presented poor functional capacity. Mean 6MWD (317.7 m),
      inspiratory muscle strength (-53.48 cmH2O) and expiratory muscle strength (69.5
      cmH2O) were all below reference values. We found that HRQL was not correlated
      with body mass index or pulmonary function. However, HRQL presented a negative
      linear correlation with age, MIP and 6MWD, as well as a positive correlation with
      the sensation of dyspnea and fatigue. CONCLUSIONS: In this study, HRQL,
      determined using the SGRQ, was severely impaired in COPD patients, who presented
      severe limitations in functional capacity, breath control and personal life.

PMID- 19390724
TI  - Noninvasive determination of inspiratory pressure in patients with spinal cord
      injury: what is the best method?
AB  - The aim of the study was to evaluate the performance of sniff nasal inspiratory
      pressure (SNIP) and MIP in individuals with spinal cord injury. We evaluated 26
      patients with spinal cord injury. Mean FVC in those with tetraplegia was 52 +/-
      19% of predicted, compared with 78 +/- 23% of predicted in those with paraplegia
      (p < 0.05). In contrast, the percentage of predicted SNIP was lower in those with
      tetraplegia than in those with paraplegia (p < 0.05). In all participants, SNIP
      correlated significantly with the level of the injury (r = 0.489; 95% CI: 0.125
      0.737). The impact that the greater discriminatory power of SNIP has on the
      diagnosis of impaired pulmonary function in spinal cord-injured patients should
      be investigated further.

PMID- 19390725
TI  - Prevalence of active and passive smoking in a population of patients with asthma.
AB  - Smoking causes an intense inflammatory reaction in the airways and is associated
      with worse clinical outcomes in patients with asthma. The objective of this study
      was to determine the prevalence of active and passive smoking in a population of
      patients with asthma. The sample of asthma patients (n = 100) consisted of 47
      nonsmokers, 33 former smokers, 17 passive smokers and 3 active smokers. Most had
      moderate or severe asthma. Mean exhaled CO was 9.34 ppb in smokers, 4.19 ppb in
      passive smokers, 3.98 ppb in nonsmokers and 3.98 ppb in former smokers. We
      conclude that the prevalence of exposure to tobacco smoke is high among asthma
      patients.

PMID- 19390726
TI  - Computed tomography findings of postoperative complications in lung
      transplantation.
AB  - Due to the increasing number and improved survival of lung transplant recipients,
      radiologists should be aware of the imaging features of the postoperative
      complications that can occur in such patients. The early treatment of
      complications is important for the long-term survival of lung transplant
      recipients. Frequently, HRCT plays a central role in the investigation of such
      complications. Early recognition of the signs of complications allows treatment
      to be initiated earlier, which improves survival. The aim of this pictorial
      review was to demonstrate the CT scan appearance of pulmonary complications such
      as reperfusion edema, acute rejection, infection, pulmonary thromboembolism,
      chronic rejection, bronchiolitis obliterans syndrome, cryptogenic organizing
      pneumonia, post-transplant lymphoproliferative disorder, bronchial dehiscence and
      bronchial stenosis.

PMID- 19390727
TI  - Pulmonary and extrapulmonary coccidioidomycosis: three cases in an endemic area
      in the state of Ceara, Brazil.
AB  - Coccidioidomycosis, a fungal illness acquired by the inhalation of arthroconidia
      of Coccidioides sp., was first described in 1894. Coccidioidomycosis is mainly
      restricted to areas with arid climate, alkaline soil and low rainfall.
      Consequently, most of the reported cases in Brazil have occurred in the
      northeastern region. We report three cases of pulmonary coccidioidomycosis
      occurring between 2005 and 2006 in an endemic area in the state of Ceara, Brazil.
      The three patients were immunocompetent adult males, hunters of armadillos
      (Dasypus novemcinctus), with complaints of cough, fever, dyspnea and pleuritic
      pain. All three patients presented pulmonary involvement, and only one also
      presented cutaneous lesions. Chest X-rays and CT scans of the patients revealed
      characteristic coccidioidomycosis lesions. The diagnosis was confirmed by
      serological testing. All of the patients evolved to cure after antifungal
      treatment.

PMID- 19390728
TI  - Mucoepidermoid carcinoma of the trachea mimicking asthma.
AB  - In cases of recent asthma in which clinical control with the usual treatment
      (corticosteroids and bronchodilator) is unsatisfactory, it is important to
      consider other diagnoses, such as congestive heart failure, gastroesophageal
      reflux or other forms of airway obstruction. We report the case of a female
      patient with mucoepidermoid carcinoma of the trachea mimicking asthma. The
      patient presented cough and wheezing, as well as abnormal spirometry results with
      an obstructive pattern that was responsive to bronchodilators. One year later,
      the patient presented clinical and spirometric worsening. The chest X-ray
      revealed no abnormalities. A CT scan showed a vegetative lesion obstructing the
      tracheal lumen and located 1 cm from the carina. Fiberoptic bronchoscopy showed a
      finding similar to a bronchial carcinoid tumor. The anatomopathological diagnosis
      made after surgical resection was low-grade mucoepidermoid carcinoma, without
      lymph node involvement. Although the flow-volume curve was not suggestive of
      upper airway obstruction, the spirometry performed after the surgery showed a
      significant reduction in the degree of obstruction and greater reversibility
      after bronchodilator use. There was no evidence of recurrence of the disease or
      of the symptoms after a two-year follow-up period.

PMID- 19390729
TI  - Osteitis after BCG vaccination.
AB  - The authors report the case of a 21-month-old boy with an osteolytic lesion in
      the proximal region of the right humerus. Based on the clinical history and
      histological findings, the authors suspected osteitis following BCG vaccination.
      Symptoms remitted after antituberculosis therapy was initiated, and the patient
      presented radiological improvement. The authors describe this uncommon entity in
      pediatric practice and call attention to possible complications of BCG
      vaccination.

PMID- 19390730
TI  - [Adherence to treatment in patients with cystic fibrosis].

PMID- 19390732
TI  - Etiological agents of diarrhea in patients infected by the human immunodeficiency
      virus-1: a review.
AB  - Despite the importance of understanding the epidemiology of agents responsible
      for infectious diarrhea in human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome (AIDS) population, the number of articles about this
      subject is relatively few. The current article summarizes published data on
      bacterial, fungal, viral and parasitic enteropathogens in the HIV/AIDS
      seropositive subjects in different countries, regions and localities. In general,
      there is a great difference in the frequencies of etiological agents due to
      factors which include immune status, geographical location, climate and
      socioeconomic conditions. It is important to stress that a great prevalence of
      infection by emergent agents has been reported in the more advanced stages of
      AIDS. Therefore, to establish specific treatment depends directly on knowledge of
      these agents and risk factors associated to their distribution. Moreover, the
      colonization by potential pathogenic agents verified in these individuals is high
      thus implicating that they act as carriers. Finally, public health measures of
      control and prevention must take into consideration the regional previously
      identified enteropathogens, especially in areas where HIV prevalence is high.

PMID- 19390733
TI  - Frequency of human toxocariasis in a rural population from Cajamarca, Peru
      determined by DOT-ELISA test.
AB  - The aim of this study was to estimate the frequency of human toxocariasis in
      Cauday district, Cajamarca, Peru, using a dot-ELISA test. From June to October
      2005, a total of 256 adult subjects were studied. Blood samples were collected
      for serology by a dot-ELISA test and for hematological examination.
      Parasitological examination was also carried out in stool samples to check cross
      reactions in the dot-ELISA. The frequency observed was 44.92%, with a significant
      higher proportion of positivity in male subjects. From subjects with positive
      serology, 45.6% had respiratory symptoms, 40.44% abdominal pain, 32.35% hepatic
      symptoms, 14.7% cutaneous signs, 13.23% ocular manifestations, 43.38%
      eosinophilia, and all of these were statistically associated to serology. Among
      the population evaluated, 90.23% (231/256) were parasitized. From subjects with
      positive serology, 92.17% had at least one intestinal parasite and the most
      frequent were: Blastocystis hominis (68.38%), Giardia lamblia (28.68%),
      Hymenolepis nana (20.0%), Ascaris lumbricoides (15.65%), Entamoeba histolytica/E.
      dispar (13.24%), Cyclospora cayetanensis (4.41%), Cryptosporidium sp. (1.47%),
      Enterobius vermicularis (0.87%), Strongyloides stercoralis (0.87%), Taenia sp.
      (0.87%), and Trichuris trichiura (0.87%). The rate of false positives in the dot
      ELISA test was improved by serum absorption each with A. suum antigens, with a
      decrease of cross-reactions. In conclusion, human toxocariasis is highly frequent
      in this population and some risk factors like dog/cat ownership, presence of pets
      within house, and previous history of geophagia were observed in the present
      study.

PMID- 19390734
TI  - Muscular strength decrease in Rattus norvegicus experimentally infected by
      Toxocara canis.
AB  - The muscular strength of experimental infected Rattus norvegicus with 3rd. stage
      Toxocara canis larvae was investigated. Fifty Wistar rats, divided in three
      groups (G1-20 rats infected by 300 eggs of T. canis; G2-20 rats infected by 2,000
      eggs of T. canis and G3-10 rats without infection) had been used. Ten and 30 days
      after infection the muscular strength in the fore-feet of the rats was checked;
      at the same time, the body weight was determined. No significative differences in
      the body weight were noted among the infected and control rats in both occasions.
      Otherwise, an impairment on the muscular strength was observed in rats infected
      with T. canis 30 days after inoculation.

PMID- 19390735
TI  - Schistosoma mansoni and other larval trematodes in Biomphalaria tenagophila
      (Planorbidae) from Guarulhos, Sao Paulo State, Brazil.
AB  - A total of 909 Biomphalaria tenagophila were collected from two areas in
      Guarulhos (Metropolitan area of Sao Paulo, Sao Paulo State, Brazil) to assess
      larval trematode infections. In all collection sites, only this species was found
      and 183 (20.13%) harbored trematode infections. In these collections, four
      morphologically distinguishable types of cercariae were identified by confocal
      microscopy. Xiphidiocercaria (Cercaria lutzi) was the most common type of
      cercaria recovered, contributing 76.5% of all infections. Schistosoma mansoni
      cercariae were recovered and comprised the total of 13.11%. Strigea cercaria
      (Cercaria caratinguensis) and Brevifurcate pharyngeate Clinostomatoide cercaria
      (Cercaria ocellifera) contributed 8.33% and 2.22% of all infections,
      respectively. Double infections (S. mansoni and C. lutzi) were found in twelve
      snails, contributing 6.55% of all infections. In all sites studied, small
      vertebrates were found in snail habitats and it was observed human contact with
      the water. The presence of trematode infected snails in large cities has public
      health implications. It further provides a starting point for some comprehensive
      studies on snail-related aspects of transmission and biology of trematode of
      medical and veterinary importance.

PMID- 19390736
TI  - Immunoperoxidase technique using an anti-Leishmania (L.) chagasi hyperimmune
      serum in the diagnosis of culture-confirmed American tegumentary leishmaniasis.
AB  - The present study reports the production of the rabbit anti-Leishmania (L.)
      chagasi hyperimmune serum, the standardization of the immunohistochemistry (IHC)
      technique and the evaluation of its employment in cutaneous leishmaniasis (CL)
      lesions diagnosed by Leishmania sp. culture isolation. Thirty fragments of active
      CL lesions were examined as well as 10 fragments of cutaneous mycosis lesions as
      control group. IHC proved more sensitive in detecting amastigotes than
      conventional hematoxylin-eosin (HE) stained slides: the former was positive in 24
      (80%) biopsies whereas the latter, in 16 (53%) (p = 0.028). The reaction stained
      different fungus species causing cutaneous mycosis. Besides, positive reaction
      was noticed in mononuclear and endothelial cells. Nevertheless, this finding was
      present in the control group biopsies. It is concluded that IHC showed good
      sensitivity in detecting amastigotes.

PMID- 19390737
TI  - Comparison of small mammal prevalence of Leishmania (Leishmania) mexicana in five
      foci of cutaneous leishmaniasis in the State of Campeche, Mexico.
AB  - In the Yucatan Peninsula of Mexico, 95% of the human cases of Cutaneous
      Leishmaniasis are caused by Leishmania (Leishmania) mexicana with an incidence
      rate of 5.08 per 100,000 inhabitants. Transmission is limited to the winter
      months (November to March). One study on wild rodents has incriminated Ototylomys
      phyllotis and Peromyscus yucatanicus as primary reservoirs of L. (L.) mexicana in
      the focus of La Libertad, Campeche. In the present study, the prevalence of both
      infection and disease caused by L. (L.) mexicana in small terrestrial mammals
      were documented during five transmission seasons (1994-2004) in five foci of
      Leishmaniasis in the state of Campeche. Foci separated by only 100 km, with
      similar relative abundances of small mammals, were found to differ significantly
      in their prevalence of both symptoms and infection. Transmission rates and
      reservoir species seemed to change in space as well as in time which limited the
      implementation of effective control measures of the disease even in a small
      endemic area such as the south of the Yucatan Peninsula.

PMID- 19390738
TI  - Neurotoxic activity and ultrastructural changes in muscles caused by the brown
      widow spider Latrodectus geometricus venom.
AB  - Brown widow spider (Latrodectus geometricus) venom (BrWSV) produces few local
      lesions and intense systemic reactions such as cramps, harsh muscle pains,
      nausea, vomiting and hypertension. Approximately 16 protein bands under reducing
      conditions and approximately 14 bands under non-reducing conditions on a 12.5%
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis were observed.
      Neurotoxic clinical manifestations were confirmed in vivo, while proteolytic
      activity was demonstrated on gelatine film. Severe ultrastructural damages in
      mice skeletal muscles were observed at 3, 6, 12 and 24 h postinjection with at
      total of 45 microg of venom protein. Infiltration of eosinophils and ruptures of
      the cellular membranes were observed in the muscles along with swelling of the
      nuclear cover and interruption of the collagen periodicity. Altered mitochondrias
      and autophage vacuoles, nuclear indentation and mitochondria without cristae,
      slight increment of intermyofibrillar and subsarcolemic spaces and myelinic
      figures formation were also observed. In the capillary, endothelial membrane
      unfolding into the lumen was noticed; along with myelinic figures compatible with
      a toxic myopathy. Swollen sarcotubular systems with lysis of membrane, intense
      mitochondria autophagia and areas without pinocytic vesicles were observed.
      Swollen mitochondria surrounded by necrotic areas, myofibrillar disorganization
      and big vacuolas of the sarcotubular system, degenerated mitochondrium with
      formation of myelinic figure was seen. Glycogenosomes with small particulate,
      muscle type glycogen was noticed. Autophagic vacuole (autophagolysosomes) and
      necrotic areas were also noticed. These damages may be due to interactive effects
      of the multifactorial action of venom components. However, Latrodectus
      geometricus venom molecules may also be utilized as neuro therapeutic tools, as
      they affect neuronal activities with high affinity and selectivity. To our
      knowledge, the present study is the first ultrastructural report in the
      literature of muscle injuries and neurological and proteolytic activities caused
      by BrWSV.

PMID- 19390739
TI  - Tungiasis in schoolchildren in Criciuma, Santa Catarina State, South Brazil.
AB  - Tungiasis is a common parasitic skin disease in Brazil, caused by the flea Tunga
      penetrans. We conducted a cross-sectional study to evaluate the occurrence of
      infestation with T. penetrans in primary schoolchildren in Criciuma, Santa
      Catarina State (South Brazil). In total, 917 children (6-10 years) of 68 schools
      were included in the study (11% of target population). Physical examination was
      followed by residential visits of those infested, to assess housing conditions
      and to interview the children's guardians. Of the 917, 15 (1.6%) children were
      infested with the parasite. The prevalence was twice as high in females (10
      children--2.2%) as compared to males (five children--1.1%), but due to the low
      number of infested individuals, the difference was statistically not significant
      (p = 0.18). The mean number of lesions found was 1.4 per child. One child
      presented bacterial superinfection. Of the 15 children infested, 10 (66.7%)
      studied in schools built on pyritiferous soil. The families of 12 children
      (79.9%) had been living in the area in which the study was conducted for less
      than eight years and were considered underprivileged families with the head of
      the household having a low education status. We conclude that in Criciuma
      tungiasis occurs in primary school children, but prevalence and parasite load are
      low.

PMID- 19390740
TI  - Relationship between plasma and red blood cell concentrations of quinine in
      Brazilian children with uncomplicated Plasmodium falciparum malaria on oral
      therapy.
AB  - We determined the relationship between plasma and red blood cell concentrations
      of quinine in children with uncomplicated falciparum malaria from an endemic area
      of Amazonian region. Quinine was determined by high performance liquid
      chromatography with ultraviolet detection. In the steady state the ratio between
      plasma and red blood cell quinine concentration was 1.89 +/- 1.25 ranging from
      1.05 to 2.34. This result demonstrated that quinine do not concentrate in red
      blood cell of Brazilian children and characterize the absence of interracial
      difference in this relationship.

PMID- 19390741
TI  - Indications of carbapenem resistance evolution through heteroresistance as an
      intermediate stage in Acinetobacter baumannii after carbapenem administration.
AB  - We describe an in vivo evolution of an antimicrobial profile from susceptibility
      to full-resistance to carbapenems, with heteroresistance as an intermediate
      stage, in an Acinetobacter baumannii strain. Heteroresistance was characterized
      by the growth of sub-populations within the susceptibility halo in both disk
      diffusion and Etest. PCRs for the main A. baumannii carbapenemases were negative.
      The exact resistance mechanism, diagnostic methods and clinical relevance of
      heteroresistance in A. baumannii warrant further investigations. This is the
      first description of such phenomenon in vivo and the second report of
      heteroresistance to carbapenems in A. baumannii.

PMID- 19390742
TI  - Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of
      an opportunistic pathogen.
AB  - We described a case of a 27-year old male patient with skin and soft tissue
      infection of a neoplastic lesion caused by Corynebacterium striatum, an organism
      which has been rarely described as a human pathogen. Identification was confirmed
      by DNA sequencing. Successful treatment with penicillin was achieved. The role of
      the C. striatum as an emerging opportunistic pathogen is discussed.

PMID- 19390743
TI  - Current status of Blastocystis terminology.

PMID- 19390744
TI  - Association of angiotensin-converting enzyme activity and polymorphism with
      echocardiographic measures in familial and nonfamilial hypertrophic
      cardiomyopathy.
AB  - Angiotensin-converting enzyme (ACE) activity and polymorphism contribute
      significantly to the prognosis of patients with cardiomyopathy. The aim of this
      study was to determine the activity and type of ACE polymorphism in patients with
      familial and nonfamilial hypertrophic cardiomyopathy (HCM) and to correlate these
      with echocardiographic measurements (echo-Doppler). We studied 136 patients (76
      males) with HCM (69 familial and 67 nonfamilial cases). Mean age was 41 +/- 17
      years. DNA was extracted from blood samples for the polymerase chain reaction and
      the determination of plasma ACE levels. Left ventricular mass, interventricular
      septum, and wall thickness were measured. Mean left ventricular mass index,
      interventricular septum and wall thickness in familial and nonfamilial forms were
      154 +/- 63 and 174 +/- 57 g/m(2) (P = 0.008), 19 +/- 5 and 21 +/- 5 mm (P =
      0.02), and 10 +/- 2 and 12 +/- 3 mm (P = 0.0001), respectively. ACE genotype
      frequencies were DD = 35%, ID = 52%, and II = 13%. A positive association was
      observed between serum ACE activity and left ventricular mass index (P = 0.04).
      Logistic regression showed that ACE activity was twice as high in patients with
      familial HCM and left ventricular mass index >or=190 g/m(2) compared with the
      nonfamilial form (P = 0.02). No other correlation was observed between ACE
      polymorphisms and the degree of myocardial hypertrophy. In conclusion, ACE
      activity, but not ACE polymorphisms, was associated with the degree of myocardial
      hypertrophy in the patients with HCM.

PMID- 19390745
TI  - Validation of a food frequency questionnaire for women with osteoporosis.
AB  - The importance of nutrient intakes in osteoporosis prevention in treatment is
      widely recognized. The objective of the present study was to develop and validate
      a FFQ for women with osteoporosis. The questionnaire was composed of 60 items,
      separated into 10 groups. The relative validation was accomplished through
      comparison of the 3-Day Food Record (3DR) with the FFQ. The 3DR was applied to 30
      elderly women with confirmed osteoporosis, and after 45 days the FFQ was
      administrated. Statistical analysis comprised the Kolmogorov-Smirnov, Student T
      test and Pearson correlation coefficient. The agreement between two methods was
      evaluated by the frequency of similar classification into quartiles, and by the
      Bland-Altman method. No significant differences between methods were observed for
      the mean evaluated nutrients, except for carbohydrate and magnesium. Pearson
      correlation coefficients were positive and statistically significant for all
      nutrients. The overall proportion of subjects classified in the same quartile by
      the two methods was on average 50.01% and in the opposite quartile 0.47%. For
      calcium intake, only 3% of subjects were classified in opposite extreme quartiles
      by the two methods. The Bland-Altman analysis demonstrated that the differences
      obtained by the two methods in each subject were well distributed around the mean
      of the difference, and the disagreement increases as the mean intake increases.
      These results indicates that the FFQ for elderly women with osteoporosis
      presented here is highly acceptable and is an accurate method that can be used in
      large-scale or clinical studies for evaluation of nutrient intakes in a similar
      population.

PMID- 19390746
TI  - The effect of protein malnutrition on the capacity for protein synthesis during
      wound healing.
AB  - OBJECTIVES: It has been shown that wound healing in the rat is associated with
      increased protein synthesis at the site of the wound 48 hours after surgical
      trauma. The aim of the current study was to examine the effect of protein
      malnutrition prior to abdominal surgery on the capacity for muscle protein
      synthesis both at the site of the wound and in undamaged abdominal muscle. DESIGN
      AND MEASUREMENTS: Thirty-two rats were randomly assigned to a low or high protein
      diet (3% and 20% casein respectively). After two weeks, half the rats in each
      group underwent abdominal surgery. Forty-eight hours after the operation all the
      animals were killed and tissues were analysed for RNA and protein contents.
      RESULTS: The capacity for protein synthesis, as indicated by the RNA:protein
      ratio, was increased at the site of the healing wound. The low protein diet
      caused a decrease in the capacity for protein synthesis in unoperated animals but
      did not prevent the increase associated with wound healing. CONCLUSION: The
      capacity to increase protein synthesis during wound healing is protected against
      the effects of malnutrition, indicating that it has a high biological priority.

PMID- 19390747
TI  - Dietary factors in relation to daily activity energy expenditure and mortality
      among older adults.
AB  - OBJECTIVES: To examine the association between dietary factors to daily activity
      energy expenditure (DAEE) and mortality among older adults. DESIGN AND SETTING: A
      sub-study of Health, Aging, and Body Composition study. PARTICIPANTS: 298 older
      participants (aged 70-82 years) in the Health, Aging, and Body Composition Energy
      Expenditure sub-study. MEASUREMENTS: Dietary factors, DAEE, and all-cause
      mortality were measured in 298 older participants. Dietary factors include
      dietary intake assessed by the Block Food Frequency Questionnaire (FFQ), Healthy
      Eating Index (HEI), and self-reported appetite and enjoyment of eating. DAEE was
      assessed using doubly labeled water. All-cause mortality was evaluated over a 9
      year period. RESULTS: Participants in the highest tertile of DAEE were more
      likely to be men and to report having a 'good' appetite; BMI among men,
      proportion married, IL-6 and CRP levels and energy intake were also higher. Fewer
      black participants were in the 'good' HEI category. Participants in the 'good'
      HEI category had higher cognitive scores and a higher education level.
      Participants who reported improvement in their appetite as well as participants
      who reported a 'good' appetite were at lower risk for mortality (HR (95% CI):
      0.42 (0.24-0.74) and 0.50 (0.26-0.88), respectively) even after adjusting for
      DAEE, demographic, nutritional and health indices. CONCLUSIONS: We showed an
      association between DAEE and appetite and mortality among well-functioning,
      community-dwelling older adults. These findings may have some practical use for
      the health providers. Inclusion of a question regarding appetite of an elderly
      patient may provide important information regarding risk for health deterioration
      and mortality.

PMID- 19390748
TI  - Comorbidity and clinical features in elderly patients with dementia: differences
      according to dementia severity.
AB  - OBJECTIVES: To evaluate comorbidity and clinical features in elderly patients
      with dementia to determine differences according to dementia severity. DESIGN:
      Observational study with medical record review. SETTING: Eight hospitals in the
      Barcelona area. PARTICIPANTS: 515 consecutive admissions aged > 64 years with
      dementia, 89.1% of whom lived in the community. MEASUREMENTS: We collected data
      on sociodemographic variables, type of dementia, Barthel Index (BI), Lawton and
      Brody Index (LI), Mini-Mental State Examination (MMSE), Charlson Index and the
      total number of drugs chronically prescribed. We stratified the population into
      two groups according to disease severity with the Global Deterioration Scale
      (GDS): mild-moderate (GDS 3-5) and severe (GDS 6-7). RESULTS: There were a total
      of 515 participants of which 364 females (70%) and 151 males with a mean age of
      81 +/- 6 years old. The total number of chronic prescription drugs was 5.6 +/-
      2.4. The mean Charlson Index score was 2 +/- 1.2. The 270 (52.5%) patients with a
      GDS score of 3-5 were compared with the 245 patients with a GDS score of 6-7. In
      the multivariate analysis, a GDS score of 6-7 was associated with poorer LI, BI,
      and MMSE scores and greater neuroleptic therapy. CONCLUSIONS: Important
      comorbidity conditions are common in elderly individuals with dementia. The
      patients with more severe dementia had poor functional status and higher
      frequency of neuroleptic use. Medical comorbidities should be taken into account
      in the management of patients with dementia.

PMID- 19390749
TI  - State of the art in aspiration assessment and the idea of a new non invasive
      predictive test for the risk of aspiration in stroke.
AB  - BACKGROUND: Dysphagia is a common but severe complication in acute stroke. New
      bedside tests are necessary to assess the risk of aspiration and avoid
      unnecessary alimentary restrictions but they must be completed by evaluated
      instruments. OBJECTIVE: We evaluated the prognostic validity of the recognition
      of forms (rf) test related to the assessment by speech and language therapists
      (SLT). DESIGN: Double blinded screening tests. SETTING: Geriatric department of
      general hospital. SUBJECTS: 50 patients with acute stroke admitted consecutively.
      METHODS: All patients were assessed by SLT, mini mental status test, short test
      for assessing deficits of memory and attention and abilities of daily living
      test. The rf-test was performed twice with a two week interval. RESULTS:
      Assessment by SLT demonstrated aspiration in 29 of 50 patients. 18 patients
      failed the rf-test, giving a specificity of 90% (positive predictive value 89%),
      a sensitivity of 55% (negative predictive value 59%). 5 of 7 patients with
      aspiration pneumonia failed the test. Test-retest-correlation was 0,827.
      Performance in the rf-test was related significantly to results of the activities
      of daily living-test. CONCLUSIONS: Bedside tests to exclude aspiration in
      patients with acute stroke are necessary. No test so far combines high
      sensitivity with acceptable specificity. Compared to other bedside tests the rf
      test has a high specificity while sensitivity is low. On behalf of good
      predictivity rf-test may be an interesting supplement to swallow tests in case of
      stroke and seems to be a candidate for more extended studies.

PMID- 19390750
TI  - C-reactive protein and fibrinogen of bedridden older patients in a six-month
      vitamin D supplementation trial.
AB  - OBJECTIVE: To elucidate the association between vitamin D status, C-reactive
      protein (CRP) and fibrinogen. DESIGN: Secondary analysis of a randomised double
      blind placebo controlled trial. SETTING: Four longterm care hospitals (1215 beds)
      in Helsinki, Finland. PARTICIPANTS: 218 long-term inpatients aged over 65 years.
      INTERVENTION: Eligible patients (n = 218) were randomized to receive 0 IU/d, 400
      IU/d, or 1200 IU/d cholecalciferol for six months. METHODS: Plasma 25
      hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), high sensitive CRP,
      fibrinogen, amino-terminal propeptide of type I procollagen (PINP), and carboxy
      terminal telopeptide of type I collagen (ICTP) were measured. RESULTS: The
      patients were aged (84.5 +/- 7.5 years), vitamin D deficient (25-OHD = 23 +/- 10
      nmol/l), chronically bedridden and in stable general condition. The mean baseline
      CRP and fibrinogen were 10.86 mg/l (0.12 mg/l - 125.00 mg/l) and 4,7 g/l (2.3 g/l
      - 8.6 g/l), respectively. CRP correlated with ICTP (r = 0.217, p = 0.001), but
      not with vitamin D status. Supplementation significantly increased 25-OHD
      concentrations, but the changes in CRP and fibrinogen were insignificant and
      inconsistent. The post-trial CRP concentrations (0.23 mg/l -138.00 mg/l)
      correlated with ICTP (r = 0.156, p < 0.001), but no association was found with
      vitamin D status. The baseline and post-trial fibrinogen correlated with CRP,
      only. CONCLUSIONS: CRP concentrations are associated with bone turnover, but not
      with vitamin D status, and vitamin D supplementation has no major effect on CRP
      or fibrinogen concentrations in bedridden older patients.

PMID- 19390751
TI  - Riboflavin supplementation and biomarkers of cardiovascular disease in the
      elderly.
AB  - BACKGROUND: High levels of total plasma homocysteine are potentially harmful in
      the elderly. OBJECTIVE: To investigated the effects of oral riboflavin
      supplementation on plasma total homocysteine, ferritin, uric acid and C-reactive
      protein concentration in elderly people with a low riboflavin status. We
      performed a four-week randomized, placebo-controlled, double-blind trial of
      riboflavin supplementation in seven Portuguese day social centers. DESIGN: Eighty
      eight individuals (66.7% female), aged between 60 and 94 years, volunteered to
      participate in the study following interview. Forty-two subjects, with an
      erythrocyte glutathione reductase activation coefficient (EGRAC) >or= 1.2, were
      included in the intervention trial. All subjects gave informed consent. Study
      subjects were administered 10 mg riboflavin (n=21) or placebo (n=21) each day for
      28 days. RESULTS: Riboflavin supplementation significantly decreased plasma tHcy
      (P=0.005) and EGRAC (P=0.014), but not plasma ferritin, uric acid or C-reactive
      protein. CONCLUSIONS: In this elderly group, we found that 10 mg/day oral
      riboflavin supplementation lowered plasma homocysteine concentrations in subjects
      with low riboflavin status.

PMID- 19390753
TI  - Varying insulin use in older hospitalized patients with diabetes.
AB  - OBJECTIVE: Observation of insulin use in consecutive hospitalized diabetic older
      patients in acute care wards with reference to nutritional intakes, measures of
      functional status, and varying clinical situations. METHODS: Prospective case
      study in a geriatric medicine ward with CGA, dietary intake measure and used
      insulin dosage. RESULTS: Among 600 inpatients, 90 diabetic subjects were found.
      Only 12.2 % diabetic patients had MMSE > 23 and 23.3% were unable to eat without
      assistance. During the stay 54 patients had received insulin. From admission to
      discharge or death, doses were 0.39 to 0.19 U/kg (SD 0.41-0.15) during palliative
      care, 0.43 to 0.45 U/kg (SD 0.20-0.20) in the event of failure of oral therapy,
      0.38 to 0.42 U/kg (SD 0.18-0.25) if creatinine clearance was 30 ml/min or lower,
      and 0.38 to 0.27 U/kg (SD 0.24-0.26) in critical diseases. Dietary intake
      increased in all during the stay with an energy intake close to 20 kCal/kg/d at
      discharge, except for those in palliative care, who had a final intake of 8.2
      kCal/kg/d (SD 9.1). CONCLUSION: Insulin treatment guidelines adapted to this
      frail diabetic population are necessary.

PMID- 19390752
TI  - Usage of megestrol acetate in the treatment of anorexia-cachexia syndrome in the
      elderly.
AB  - The aim of this review is to assess the efficacy and safety of megestrol acetate
      (MA) in geriatric cachexia. The paper presented here reviews a previously
      published study of MA use in 69 patients in a randomized double blind placebo
      controlled trial. This paper will also address the underlying pathogenesis of
      cachexia (specifically, the role of cytokines) along with the use of MA, its
      mechanism of action and its side effects. OBJECTIVE: To compare the effects of MA
      oral suspension (O.S.), 800 mg/day, versus placebo on weight in geriatric nursing
      home patients with weight loss or low body weight. DESIGN: Twelve weeks,
      randomized, double-blind, placebo-controlled trial with a 13-week follow-up
      period. PATIENTS: Northport VAMC Nursing home patients with weight loss of * 5%
      of usual body weight over the past 3 months, or body weight 20% below their ideal
      body weight. INTERVENTIONS: Patients were randomly assigned to receive placebo or
      MA 800 mg/d for 12 weeks and were then followed for 13 weeks off treatment and
      mortality 4 years post treatment. MEASUREMENTS: Primary outcome- weight and
      appetite change. Secondary outcome-sense of well being, enjoyment of life, change
      in depression scale, laboratory nutrition parameters, energy intake counts, body
      composition, and adverse events. RESULTS: At 12 weeks there were no significant
      differences in weight gain between treatment groups, while MA-treated patients
      reported significantly greater improvement in appetite, enjoyment of life, and
      well being. At week 25 (3 months after treatment), 61.9% of MA-treated patients
      had gained * 1.82 kg (4 lbs) compared to 21.7% of placebo patients. There was no
      difference in survival between MA and placebo groups. Considering possible
      confounders, higher initial IL-6, initial TNFR-p75 levels, and final neutrophil
      percentage were associated with elevated mortality, whereas higher initial pre
      albumin, initial albumin, final pre-albumin, final albumin and final weight gain
      were associated with decreased death.

PMID- 19390754
TI  - Sarcopenic-obesity and cardiovascular disease risk in the elderly.
AB  - OBJECTIVES: To determine: 1) whether sarcopenic-obesity is a stronger predictor
      of cardiovascular disease (CVD) than either sarcopenia or obesity alone in the
      elderly, and 2) whether muscle mass or muscular strength is a stronger marker of
      CVD risk. DESIGN: Prospective cohort study. PARTICIPANTS: Participants included
      3366 community-dwelling older (>or= 65 years) men and women who were free of CVD
      at baseline. MEASUREMENTS: Waist circumference (WC), bioimpedance analysis, and
      grip strength were used to measure abdominal obesity, whole-body muscle mass, and
      muscular strength, respectively. Subjects were classified as normal, sarcopenic,
      obese, or sarcopenic-obese based on measures of WC and either muscle mass or
      strength. Participants were followed for 8 years for CVD development and
      proportional hazard regression models were used to compare risk estimates for CVD
      in the four groups after adjusting for age, sex, race, income, smoking, alcohol,
      and cognitive status. RESULTS: Compared with the normal group, CVD risk was not
      significantly elevated within the obese, sarcopenic, or sarcopenic-obese groups
      as determined by WC and muscle mass. When determined by WC and muscle strength,
      CVD risk was not significantly increased in the sarcopenic or obese groups, but
      was increased by 23% (95% confidence interval: 0.99-1.54, P=0.06) within the
      sarcopenic-obese group. CONCLUSION: Sarcopenia and obesity alone were not
      sufficient to increase CVD risk. Sarcopenic-obesity, based on muscle strength but
      not muscle mass, was modestly associated with increased CVD risk. These findings
      imply that strength may be more important than muscle mass for CVD protection in
      old age.

PMID- 19390755
TI  - Effect of smoking on the accumulation of deficits, frailty and survival in older
      adults: a secondary analysis from the Canadian Study of Health and Aging.
AB  - OBJECTIVES: Smoking has adverse effects on a variety of organ systems but little
      is known about the relationship between smoking and frailty. We aimed to
      investigate differences in health status between smoking and non smoking older
      adults. DESIGN AND SETTING: The Canadian Study of Health and Aging, a nationally
      representative cohort study. PARTICIPANTS: Nine thousand and eight community
      dwelling men and women age 65 years and over at baseline. MEASUREMENTS: Smoking
      status was determined using a Self-Assessed Risk Factor Questionnaire.
      Comparisons were made between never smokers, light smokers and heavy smokers with
      heavy smokers defined as those who smoked >or= 1 pack per day for 20 years or
      more. A frailty index (FI) generated from 40 self-reported health deficits was
      also modified to exclude 5 variables that could be directly attributed to smoking
      (e.g. cough). Decedent information was collected over 10 years. RESULTS: Average
      FI values increased exponentially with age. For both men and women, heavy smokers
      were the most frail, light smokers had intermediate frailty status and never
      smokers were fittest. Modification of the FI did not impact these differences.
      Heavy smokers had significantly worse mortality than non smokers and higher rates
      of death in smokers persisted in the oldest old. 120 month survival curves,
      grouped for age, sex and smoking status showed that male smokers > 75 years had
      the highest mortality rates. CONCLUSIONS: Smoking causes poorer health status at
      older ages which can be captured by the frailty index. Higher rates of death in
      smokers persist in the oldest old, with no emergence of "survivors" with fitness
      or longevity advantages.

PMID- 19390756
TI  - [Volume status and central venous pressure].
AB  - Values of intramural or even transmural central venous pressure (CVP) as well as
      values of pulmonary artery occluded pressure do not correlate with the values of
      measured circulating blood volume or with responsiveness to fluid challenge. The
      veins contain approximately 70% of the total blood volume and are 30 times more
      compliant than arteries, therefore, changes in blood volume within the veins are
      associated with relatively small changes in venous pressure. The main reason for
      a lack of correlation between CVP values and blood volume is that the body does
      everything possible to maintain homeostasis and adequate transmural CVP is a must
      for cardiovascular function. The most accurate measurement of volume status would
      be the mean circulatory filling pressure (MCFP), which cannot be measured in a
      clinical setting. Stressed volume determines MCFP and directly affects venous
      return and cardiac output whereas unstressed volume is a reserve of blood that
      can be mobilized into circulation when needed. Both stressed and unstressed
      volume cannot be adequately measured. Therefore, considering the complexity of
      the physiologic feedback and clinical picture, robust reflexes and homeostatic
      mechanisms, CVP is insufficient as a surrogate parameter for assessing the volume
      status.

PMID- 19390757
TI  - Liver histopathology in brown trout (Salmo trutta f. fario) from the Tinhela
      River, subjected to mine drainage from the abandoned Jales Mine (Portugal).
AB  - The objective of this study was to compare the occurrence of toxicopathic liver
      lesions in brown trout (Salmo trutta fario) from Tinhela River near the Jales
      Mine, both before implementation (2002) and after completion of the governmental
      mitigation program (2006). Fish were caught in April 2002 and May 2006, using an
      electrofishing system at four sites: S0, reference station; S1, S2 and S3 as
      contaminated stations. In 2002, the hepatosomatic index (HSI) was significantly
      higher for trout captured at the contaminated sites S2 and S3 than in S0. After
      the rehabilitation program, the HSI of fish sampled at the contaminated sites did
      not differ from the reference group. The liver of trout caught at S0 exhibited
      the normal parenchymal and stromal architecture described for the species and
      there were no pathological abnormalities. In contrast, fish sampled at S3 and S2
      sites had diverse toxicopathic alterations. Specifically, livers from the two
      contaminated sites showed bile duct hyperplasia, often with mild epithelial
      dysplasia and fibrotic adventitial sleeve, foci of smaller and more basophilic
      hepatocytes and foci of hepatocellular necrosis; the latter conditions were
      frequently associated. Compared with the reference animals, increased
      hepatocellular vacuolization was found in livers from the polluted sites.
      Histopathological examination revealed differences among sampling sites in the
      severity and diversity of hepatic lesions clearly related to the proximity of the
      tailings. No pathological alterations were observed in the livers of brown trout
      caught in the same four areas of the Tinhela River after the mitigation program
      in 2006. In conclusion, our results supported that drainage from the abandoned
      Jales Mine had deleterious toxicological effects in brown trout. Our data
      suggested that the governmental mitigation program may have reduced the impact of
      Jales tailings.

PMID- 19390758
TI  - The power of video conferencing in surgical practice and education.

PMID- 19390759
TI  - Sacral nerve terminal motor latency in patients with or without soiling more than
      2 years after low anterior resection for low rectal cancer.
AB  - BACKGROUND: To clarify the neurologic function with respect to puborectalis
      muscle (PM) in patients after low anterior resection (LAR) for low rectal cancer,
      author examined the sacral nerve terminal motor latency (SNTML) of the PM.
      METHODS: The latency of the response in the PM following transcutaneous magnetic
      stimulation of the cauda equina at the levels from S3 to S4 by SNTML was measured
      in 33 patients after LAR. They were divided into groups. Group A, which
      experienced soiling, comprised 15 patients (11 men, 4 women) aged 58 to 77 years
      (mean 63.5 years). Group A was further divided into patients having soiling with
      mucous secretions and feces on underwear on awaking everyday (group A1, 9 cases)
      and those with soiling during the daytime only when diarrhea occurred (group A2,
      6 cases). Group B, which did not experience soiling comprised 18 patients (12
      men, 6 women), aged 47 to 76 years (mean 62.2 years). The results from the groups
      were compared with data obtained from 33 control subjects (group C), who
      comprised 23 men and 10 women, aged 47 to 74 years (mean 62.4 years). RESULTS:
      The distance of the anastomosis from the dentate line (DL) in group A1 was
      significant shorter than in groups A2 and B (p = 0.0071, p < 0.0001,
      respectively). Patients in group A displayed significant prolongation of the
      SNTML values compared with patients in groups B and C at the right, left, and
      posterior sites (all p < 0.0001). Moreover, patients in group B showed more
      extended SNTML than those in group C at all sites. Patients in group A1 exhibited
      significant prolongation of the SNTML compared with patients in groups A2 and B
      at all sites (all p < 0.0001). Moreover, patients in group A2 showed more
      prolonged SNTML than those in group B at all sites. A significant correlation was
      found between the distance of the anastomosis from the DL and the SNTML values at
      all sites of the PM (right side: r = 0.786, p < 0.0001; left side: r = 0.739, p <
      0.0001; posterior: r = 0.773, p < 0.0001). CONCLUSIONS: Soiling after LAR may be
      caused by damage to the bilateral sacral motor nerves.

PMID- 19390760
TI  - Self-perceived natural history of pelvic organ prolapse described by women
      presenting for treatment.
AB  - INTRODUCTION AND HYPOTHESIS: This study aimed to describe the self-perceived
      natural history of pelvic organ prolapse (POP) in women seeking care. METHODS:
      Women presenting to a university-based urogynecology clinic for POP (n = 107)
      completed a questionnaire including questions about how and when their prolapse
      was discovered. A urogynecologic examination including the pelvic organ prolapse
      quantification (POP-Q) was also performed. RESULTS: Forty-eight percent of these
      women sought medical attention "immediately" after discovering a bulge. The
      median time to seek care was 4 months (range from 1 month to 45 years). Twenty
      six percent associated their prolapse with a specific event (e.g., moving
      furniture or pushing a car). POP was self-discovered by 76% (81/107) of women.
      Self-discovered prolapses were larger than those diagnosed by physicians (Ba +1.3
      vs 0.1 cm, P = .03, respectively). CONCLUSIONS: Women seek medical advice within
      months of discovering their prolapse. Self-discovery is associated with higher
      stage prolapse than prolapse diagnosed by health care providers.

PMID- 19390761
TI  - How painful is multichannel urodynamic testing?
AB  - INTRODUCTION AND HYPOTHESIS: Multichannel urodynamic testing is considered to be
      the gold standard for evaluation of lower urinary tracts symptoms in women. The
      objective of this study was to assess the level of pain associated with this
      test. METHODS: We reviewed charts of women who underwent multichannel urodynamic
      testing for lower urinary tract symptoms and recorded pain levels using a
      validated visual analog pain scale of 0-10 before, during, and 1.5 h after the
      test. RESULTS: We identified 50 patients who underwent the test. Pain level
      increased mildly but significantly during the urodynamic test (1.24 +/- 0.9 vs
      0.02 +/- 0.14 p < 0.001) and decreased thereafter (0.1 +/- 0.35, p < 0.001).
      CONCLUSIONS: Multichannel urodynamic testing is associated with a low but
      significant level of pain, which generally abates shortly after the procedure. No
      correlation seems to exist between the degree of pain and various clinical and
      pelvic floor parameters.

PMID- 19390762
TI  - Transobturator adjustable tape (TOA) permits to correct postoperatively the
      tension applied in stress incontinence surgery.
AB  - INTRODUCTION AND HYPOTHESIS: The adjustable transvaginal tape (TVA) has shown to
      allow adjustment of tension thus permitting correction of postoperative
      incontinence or obstruction. An adjustable transobturator mesh has been checked.
      METHODS: Seventy-seven incontinent women received transobturator adjustable tape
      (TOA). Patients were monitored 1, 6, and 12 months post-surgery and annually
      thereafter by medical history, cough stress test, flowmetry, post-void residual
      (PVR), and incontinence quality of life, international consultation on
      incontinence-short form, and patient global impressions of improvement (PGI-I)
      questionnaires. RESULTS: After adjustment, all patients rendered continent; none
      had PVR. On no occasion was vesical catheterization necessary. Mean follow-up was
      24.7 +/- 10.3 months. Objective cure rate was 90% with 6.5% having greatly
      improved. The PGI-I questionnaire showed 90.7% of patients to be better or very
      much better than before. Q (max) was 21.3 +/- 7.2 ml/s. No infection was
      identified. Vaginal extrusion occurred in one patient. CONCLUSIONS: Our data
      demonstrate that the TOA allows postoperative adjustment of tension thus
      permitting correction of postoperative incontinence or obstruction.

PMID- 19390765
TI  - Measurement and analysis of the perforator arteries in upper extremity for the
      flap design.
AB  - The aim of this study was to provide the anatomical basis for the skin flap
      pedicled with the nutrient vessels of the cutaneous nerves and cutaneous veins of
      the upper extremity. Radio-opaque material was injected into the common carotid
      arteries of five fresh cadavers. The skin and the fascia were meticulously
      dissected, removed, and radiographed. The Photoshop CS and Scion image 4.02 were
      used to analyze the cutaneous arteries, the density of vessels, and the vascular
      territories of the perforator arteries. The results showed that the cutaneous
      arteries of the upper extremity came from 16 original arteries, and accordingly,
      the superficial tissue of the upper extremity could be divided into 16 vascular
      territories. The external diameter and the area of blood supply of each
      perforator were growing downwards from the proximum to the distal end. But the
      points at which the perforator arteries came out from the deep tissue were
      concentrated near the cutaneous nerves and cutaneous veins, and the arteries
      formed vascular chains. The density of the arteries near the cutaneous nerves and
      cutaneous veins was much higher than that of other areas. This article discussed
      the regularity of the nutrient vessels of the cutaneous nerves and veins on the
      basis of the experimental results.

PMID- 19390766
TI  - Neurocognitive functioning in the early stages of bipolar disorder: visual
      backward masking performance in high risk subjects.
AB  - INTRODUCTION: Cognitive deficits, including deficits in early information
      processing, are associated with remitted bipolar disorder. The temporal
      relationship between these deficits and the clinical course is not known. The
      current study investigated whether or not deficits in early information
      processing were present before the onset and/or during the early stages of
      bipolar disorder. METHODS: Unaffected and remitted high risk offspring of well
      characterized bipolar parents completed a visual backward masking task. For
      comparison we included a cohort of unaffected offspring of well parents and a
      clinically referred group of remitted bipolar patients. RESULTS: There was no
      evidence of a deficit in early information processing in well high risk subjects.
      As expected, the referred patient group had the highest error rates. After
      excluding the patients, interaction effect showed that the affected remitted high
      risk subjects performed differently in terms of error rates than unaffected high
      risk and control subjects. There were no significant differences in response
      times across study groups. Exploratory analyses revealed an association between a
      lifetime history of psychosis and increased errors on the task. CONCLUSIONS:
      There was no evidence of a vulnerability in early information processing in
      offspring at risk for bipolar disorder. However, there were emergent changes in
      performance in the affected remitted high risk group. Psychosis appears to be an
      important clinical correlate associated with cognitive deficits. Mapping of the
      early course of bipolar disorder and associated changes in cognition has
      important implications for establishing critical periods for intervention.

PMID- 19390767
TI  - Predicting hospital mortality using APACHE II scores in neurocritically ill
      patients: a prospective study.
AB  - Four versions of Acute Physiology and Chronic Health Evaluation are limited in
      predicting hospital mortality for neurocritically ill patients. This prospective
      study aimed to develop and assess the accuracy of a modified APACHE II model in
      predicting mortality in neurologic intensive care unit (N-ICU). A total of 653
      patients entered the study. APACHE II scores on admission, and worst 24-, 48-,
      and 72-h scores were obtained. Neurologic diagnoses on admission were classified
      into five categories: cerebral infarction, intracranial hemorrhage, neurologic
      infection, neuromuscular disease, and other neurologic diseases. We developed a
      modified APACHE II model based on the variables of the 72-h APACHE II score and
      disease category using a multivariate logistic regression procedure to estimate
      probability of death. We assessed the calibration and discrimination of the
      modified APACHE II model using the Hosmer-Lemeshow goodness-of-fit chi-squared
      statistic and area under the receiver operating characteristic curve (AU-ROC).
      The modified APACHE II model had good discrimination (AU-ROC = 0.88) and
      calibration (Hosmer-Lemeshow statistic: chi (2) = 3.707, P = 0.834). The
      discrimination of the 72-h APACHE II score for cerebral infarction, intracerebral
      hemorrhage, and neurologic infection was satisfactory, with AU-ROC of 0.858,
      0.863, and 1.000, respectively, but it was poor in discriminating for the
      categories of other neurologic diseases and neuromuscular disease. The results
      showed that our modified APACHE II model can accurately predict hospital
      mortality for patients in N-ICU. It is more applicable to clinical practice than
      the previous model because of its simplicity and ease of use.

PMID- 19390768
TI  - A case of late adult-onset dentatorubral-pallidoluysian atrophy mimicking central
      pontine myelinolysis.
AB  - We report the case of a 52-year-old man with late-onset dentatorubral
      pallidoluysian atrophy (DRPLA). MRI findings of late-onset DRPLA usually showed
      the involvement of cerebral white matter lesions with high intensity on T2
      weighted images (WI), in addition to brainstem, globus pallidus, and thalamus.
      But our patient did not present with abnormal manifestation of white matter
      lesions of the cerebrum. In addition, the appearance of pontine base was
      remarkably similar to central pontine myelinolysis (CPM). There is no reported
      case of DRPLA mimicking CPM in the literature, while there is one previous report
      of CPM with cerebellar ataxia without pyramidal tract involvement, and CPM may
      exhibit cerebellar ataxia. Although there is differentiation between CPM and
      DRPLA by the presence of the atrophy of brainstem and cerebellum, the
      characteristic MRI findings of pontine base may make it difficult to
      differentiate CPM with cerebellar ataxia from DRPLA with inconspicuous
      leukoencephalopathy. In such a situation, we should return to the clinical
      history and background of a patient, and, if necessary, DNA analysis should be
      performed for a definite diagnosis.

PMID- 19390769
TI  - Isolated unilateral ptosis and mydriasis from ventral midbrain infarction.
AB  - We report a patient who has a tremor and unilateral ptosis and mydriasis without
      extraocular muscle paresis from an intra-axial lesion demonstrated on
      neuroimaging. Previously extraocular muscles sparing partial third nerve palsy
      has been thought to be due to extra-axial lesion such as vascular compression.
      Compared to proposed models for arrangement of oculomotor fascicle, this case
      demonstrates that it is possible to damage the fibers destined for levator and
      pupillomotor function without affecting the extra-ocular muscles.

PMID- 19390770
TI  - Reliability and diagnostic efficiency of the abbreviated-diagnostic interview for
      borderlines in an adolescent clinical population.
AB  - Examine the reliability as well as the concurrent validity and diagnostic
      efficiency of the Abbreviated version of the diagnostic interview for borderlines
      revised (Ab-DIB) as a screening measure of borderline psychopathology in an
      adolescent clinical population. The Ab-DIB is a DIB-R-derived self-report
      covering the impulsiveness as well as the affect and cognitive components of the
      borderline construct. Its administration lasts 10 min. The Ab-DIB was tested on
      139 suicidal youths for reliability and concurrent validity against the DIB-R and
      the Columbia Impairment Scale (CIS). Internal consistencies and test-retest Intra
      Class-Correlations ranged from 0.80 to 0.86 and 0.77 to 0.95, respectively. ROC
      analysis yielded an area under the curve of 0.87 (p < 0.001). Sensitivity was
      0.88 and specificity ranged from 0.82 to 0.73 depending on the age-range.
      Correlation of the Ab-DIB's continuous score with the CIS was 0.42 (p < 0.001).
      In conclusion, The Ab-DIB's brief duration and psychometric properties suggest
      its utility in time-limited settings.

PMID- 19390771
TI  - Alveolar echinococcosis of the liver in children.
AB  - BACKGROUND/PURPOSE: Alveolar echinococcosis of the liver (AEL) is a zoonosis that
      is distributed in cold regions of the northern hemisphere. The disease is mostly
      found in adults and rarely in pediatric patients because it tends to be slow
      growing. PATIENTS AND METHODS: Ten Japanese pediatric patients (under 15 years
      old) with AEL have been operated on in Hokkaido University Hospital from January
      1936 to June 2008. We examined these children and revealed the characteristics of
      AEL. RESULTS: The patients included three males and seven females whose mean age
      was 10.9 years old, ranging from 7 to 15. The length of follow-up was from 3
      months to 33 years (median 19 years). Six cases were picked up by mass screening;
      nine cases who underwent hepatectomy are still alive and one case whose tumors
      were unresectable died of liver failure. CONCLUSION: Our cases indicate that some
      AEL pediatric patients advanced rapidly, so early detection is imperative. Thus,
      screening examinations are essential for children in contaminated areas and, if a
      liver tumor is found on a screening examination and diagnosed as AEL, complete
      radical resection should be performed.

PMID- 19390772
TI  - Spleen and gastrosplenic ligament preserving distal pancreatectomy under a
      minimum incision approach assisted by laparoscopy.
AB  - BACKGROUND: As a modification of hand-assisted laparoscopic pancreatectomy, we
      devised a method of spleen and gastrosplenic ligament preserving distal
      pancreatectomy, in which pancreatic resection is performed under direct vision
      extracorporeally. METHODS: The distal pancreas and spleen are pulled out of the
      peritoneal cavity through the minilaparotomy at the epigastrium following hand
      assisted laparoscopic dissection of the distal pancreas. Spleen-preserving
      pancreatectomy is performed safely under direct vision. The gastrosplenic
      ligament is also preserved to prevent splenic volvulus after the operation. The
      transected main pancreatic duct is doubly ligated, and the transected pancreatic
      stump is sewn manually. The preserved spleen and splenic vessels are placed back
      in the peritoneal cavity after resection. RESULTS: In the current study (n = 3),
      overall morbidity rate, including splenic volvulus and pancreatic fistula, was
      0%. CONCLUSION: Preservation of the gastrosplenic ligament and extracorporeal
      preparation of the transected pancreatic stump under direct vision are useful
      measures in spleen-preserving distal pancreatectomy under a minimum incision
      approach assisted by laparoscopy.

PMID- 19390773
TI  - Glucose levels during oral glucose tolerance tests and gamma-glutamyl
      transpeptidase are predictors of change from normal to impaired glucose tolerance
      in healthy middle-aged Japanese men.
AB  - We evaluated the predictors of the development from normal to impaired glucose
      tolerance (IGT) in healthy middle-aged Japanese men. Forty male subjects who
      showed normal glucose tolerance (NGT) levels based on WHO criteria and who had
      undergone 75-g OGTT annually for 10 years were selected in the database of
      medical checkups retrospectively, and divided into two groups: those retaining
      NGT and those that developed IGT. Gamma-glutamyl transpeptidase (GGT) and the
      glucose levels at 30 and 60 min were significantly associated with the
      development of IGT in the Cox proportional hazard model. However, other clinical
      characteristics and the glucose levels at pre-load and at 120 min were not
      significantly associated with the development of IGT. GGT and the glucose levels
      at 30 and 60 min after the 75-g glucose load were predictors of development from
      NGT to IGT in healthy middle-aged Japanese men.

PMID- 19390774
TI  - Treatment of ruptured anterior communicating artery aneurysm accompanying
      intracerebral hematomas: endovascular coiling followed by hematoma evacuation
      with burr hole trephination and catheterization.
AB  - INTRODUCTION: The aim of this study was to evaluate the outcome of endovascular
      coiling of ruptured anterior communicating artery (AcomA) aneurysms followed by
      intracerebral hematoma (ICH) evacuation with burr hole trephination and
      catheterization. METHODS: Twelve patients treated by coiling with subsequent ICH
      drainage with burr hole trephination and catheterization were recruited from 290
      patients with ruptured AcomA aneurysm in our hospital between January 2001 and
      June 2007. The clinical and radiographic characteristics and outcomes of the 12
      patients were retrospectively analyzed. RESULTS: All 12 patients were male, aged
      from 29 to 62 years, and had ICHs with 16-ml to 45-ml volumes; nine (75%) of them
      had frontal ICHs on the opposite side of the dominant A1. Admission Hunt-Hess
      (HH) grade was 4 in eight patients, 3 in two, and 5 in two. The treatment
      outcomes in 8 of the 12 patients were good recovery or moderately disabled
      (Glasgow Outcome Scale; GOS 5 or 4), and functionally dependent (GOS 3 or 2) in
      the other 4 patients at the 6-month clinical follow-up. There was no rebleeding
      during the follow-up (mean, 22.9 months; range, 7 to 68 months). CONCLUSION: The
      result of our series suggests that coiling with subsequent evacuation of the ICH
      with burr hole trephination and catheterization may be an alternative treatment
      option for ruptured AcomA aneurysm with an ICH requiring evacuation on the
      opposite side of the dominant A1.

PMID- 19390775
TI  - A comparison between surgical resection in combination with WBRT or
      hypofractionated stereotactic irradiation in the treatment of solitary brain
      metastases.
AB  - BACKGROUND: The standard treatment of solitary brain metastases previously has
      been tumour resection in combination with whole-brain radiation therapy (WBRT).
      Stereotactic radiotherapy has emerged as a non-invasive treatment option
      especially for small brain metastases. We now report our results on resection +
      WBRT or hypofractionated stereotactic irradiation (HCSRT) in the treatment of
      solitary brain metastases. METHODS: Between 1993 and 2004 patients with
      metastatic cancer and solitary brain metastases were selected for surgical
      resection + WBRT or HCSRT alone at the Umea University Hospital. Fifty-nine
      patients were treated with surgical resection + WBRT (34 male, 25 female, mean
      age 63.3 years). Forty-seven patients were treated with HCSRT alone (15 male, 32
      female, mean age 64.9 years). FINDINGS: In patients followed radiologically, 28%
      treated with resection + WBRT showed a local recurrence after a median time of
      8.0 months, whereas there was a lack of local control in 16% in the HCSRT group
      after a median time of 3.0 months. There was a significantly longer survival time
      for patients treated with resection + WBRT (median 7.9, mean 12.9 months)
      compared to HCSRT (median 5.0, mean 7.6 months). Even in patients with a tumour
      volume <10 cc, there was a significantly longer survival in favour of resection +
      WBRT (median 8.4, mean 17.4 months) compared to HCSRT (median 5.0, mean 7.9
      months). CONCLUSION: This retrospective and non-randomised study indicates that
      surgical resection in combination with WBRT may be an option even for small brain
      metastases suitable for treatment with HCSRT. Since survival and local control
      following resection + WBRT was at least as favourable as compared to HCSRT alone,
      tumour location and expected neurological outcome may be the strongest aspect
      when selecting treatment modality.

PMID- 19390776
TI  - Cystic craniopharyngioma: trans-sphenoidal surgery and intra-cystic apposition of
      "bleomycin wax".
AB  - BACKGROUND: The current therapeutic approach to craniopharyngioma is
      multidisciplinary. Sub-total removal, followed by adjuvant treatments, especially
      in large cystic tumours, is an accepted regime reported by many authors. CASE
      REPORT: A young patient with an intra- and suprasellar cystic craniopharyngioma
      was operated on via a microsurgical trans-sphenoidal approach, achieving sub
      total removal and bleomycin mixed with bone wax ("bleomycin wax") applied to the
      capsular remnant. RESULTS: Pre-operative neurological and endocrinological
      deficit improved after surgery. There was no evidence of tumour recurrence after
      a follow-up period of 5.4 years. CONCLUSIONS: The intra-operative use of
      "bleomycin-wax" should be limited to those patients in whom intra-operative CSF
      fistula does not occur.

PMID- 19390777
TI  - Antibiotic-impregnated ventriculo-peritoneal shunts in patients at high risk of
      infection.
AB  - PURPOSE: To determine the efficacy of antibiotic impregnated shunts (AIS) in
      reducing shunt infections in a population at high risk of shunt infection.
      METHODS: From October 2005 to October 2007, patients at high risk of infection
      (severely disabled, not able to take care of themselves, frequent nosocomial
      infections) were selected from the 198 adults who underwent shunt placement.
      RESULTS: Eighteen adults were identified (mean age 61.8 years). Six patients had
      AISs, and 12 patients had non-AISs. Groups did not differ in age, sex, type of
      hydrocephalus or hospital stay before shunting. Shunt infection occurred in 7/12
      cases of the non-AIS group (58.3%) versus no infections in the AIS group. In six
      of seven cases, infection occurred within the first 6 months after surgery. A
      prevalence of S. epidermidis was detected. CONCLUSIONS: We believe that in these
      patients AIS could be effective. Larger, prospective studies are needed in order
      to definitely address this issue.

PMID- 19390778
TI  - Spontaneous acute subdural haematoma and intracerebral haemorrhage in patient
      with HELLP syndrome: case report.
AB  - HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome can
      result in a fatal intracranial haemorrhage during the perinatal period. We report
      treatment of a 32-year-old primigravida who fell into a deep coma during labour
      with fetal distress, complicated by a spontaneous acute subdural haematoma and
      intracerebral haemorrhage. Simultaneous emergency operations, evacuation of the
      acute subdural haematoma and a caesarean section, were performed, during which a
      diagnosis of HELLP syndrome with disseminated intravascular coagulation was made.
      Both mother and infant recovered, though hemiparesis persisted in the mother.
      Patients with HELLP syndrome should be managed as high-risk, which requires an
      excellent working relationship of the physicians involved. Prompt recognition of
      intracranial haemorrhagic complications and neurosurgical intervention are
      particularly important.

PMID- 19390779
TI  - Broad-range PCR in selected episodes of prosthetic joint infection.

PMID- 19390780
TI  - Cryptococcus gattii meningoencephalitis in an immunocompetent person 13 months
      after exposure.
AB  - A 53-year old immunocompetent Swiss female is described who developed severe
      meningoencephalitis due to infection with Cryptococcus gattii 13 months following
      exposure on Vancouver Island, Canada. Diagnosis was based on cerebrospinal fluid
      (CSF) examination, i.e., positive India-ink staining, positive latex particle
      agglutination, and positive culture. Species identification was performed by
      growth on L-canavanine-glycine-bromthymol blue medium and by sequencing of the
      intergenic and internal transcribed spacer regions of the rRNA genes. After
      initial therapy with fluconazole by which the patient did not improve, therapy
      was changed to amphotericin B and flucytosine and later to high-dose fluconazole
      and amphotericin B. Despite long-term treatment and external drainage of the CSF,
      the patient's condition improved only slowly. The patient was discharged after
      132 days of hospitalization.

PMID- 19390781
TI  - A rare case of Clostridium sordellii bacteremia in an immunocompromised patient.
AB  - Clostridium sordellii is a gram-positive, anaerobic sporeforming rod with
      peritrichous flagella that is rarely associated with disease in humans. In most
      cases, infections occur after trauma, childbirth and routine gynecological
      procedures or intravenous drug abuse. C. sordellii produce several exotoxins that
      lead to progressive edema and shock, and C. sordellii infections have high
      mortality rates of up to 70%. Since its first report in 1922, only a few cases of
      bacteremia have been reported. This report describes a case of C. sordellii
      bacteremia in a patient with rectum carcinoma and liver metastases.

PMID- 19390782
TI  - Strong inhibition of replicative DNA synthesis in the developing rat cerebral
      cortex and glioma cells by roscovitine.
AB  - The effects of the cyclin-dependent kinase inhibitors roscovitine and olomoucine
      on DNA synthesis rate during normal rat brain development were studied by using
      short time (90 min) incubation. Both purine analogues at 100 microM concentration
      decreased the DNA synthesis of rat cerebral cortex in an age-dependent manner.
      The maximum inhibitory effect (approximately 90% for roscovitine, approximately
      60% for olomoucine) occurred in rats of 2-13 days postnatal age. In adult rats (>
      60 days postnatal age), the effect of both purine analogues was low. Roscovitine
      even at 200 microM concentration did not inhibit the fraction of DNA synthesis
      insensitive to hydroxyurea (unscheduled DNA synthesis (UDS)). In addition, in the
      RG2 rat glioma model, roscovitine produced a strong inhibition of DNA synthesis
      in glioma cells when compared to adult normal tissue. Since in adult rat brain
      more than 60% of DNA synthesis is related to DNA repair, usually measured as UDS,
      our results indicate that roscovitine strongly blocks ongoing DNA synthesis
      connected with replicative processes.

PMID- 19390783
TI  - Synthesis and in vitro characterization of ionone-based chalcones as novel
      antiandrogens effective against multiple clinically relevant androgen receptor
      mutants.
AB  - A crucial event in prostate cancer progression is the transition from a hormone
      sensitive to a lethal castration-refractory disease state. The antagonist-to
      agonist conversion due to mutation in AR is a critical problem with the current
      clinically used antiandrogens. We aim to identify novel antiandrogens that remain
      as a pure antagonist even in the mutated ARs. By synthesizing a series of ionone
      based chalcones, we have identified a novel chalcone (17) that is a pan
      antagonist of the wild type and the clinically relevant T877A, W741C and H874Y
      mutated ARs in luciferase reporter assays in PC-3 cells. Further, chalcone 17
      demonstrates sub-micromolar to low micromolar antiproliferative activity in
      LNCaP, MDA-PCa-2b, 22Rv1 and C4-2B prostate cancer cells, all of which express
      mutated ARs and confer resistance to the current clinically used antiandrogens.
      The results suggest that chalcone 17 could be a good candidate for further pre
      clinical development as a novel antiandrogen for advanced prostate cancer.

PMID- 19390785
TI  - Heme oxygenase-1 mediates the anti-allergic actions of quercetin in rodent mast
      cells.
AB  - OBJECTIVE AND DESIGN: We investigated the involvement of heme oxygenase (HO)-1 in
      the anti-allergic action of quercetin against degranulation of rat basophilic
      leukemia (RBL-2H3) cells, rat peritoneal mast cells, and mouse bone marrow
      derived mast cells. METHODS: The strength of allergic reaction was evaluated by
      the extent of degranulation in mast cells sensitized with various stimulants. The
      levels of HO-1, HO-2, and nuclear factor erythroid 2-related factor 2 (Nrf2)
      expressions were determined by quantitative RT-PCR, western blotting, or
      immunocytochemistry. RESULTS: Heme oxygenase activity was upregulated after short
      exposure to quercetin, followed by the induction of HO-1 expression after long
      exposure to quercetin. The inhibition of degranulation by quercetin was reversed
      using tin protoporphyrin IX (SnPP), an HO-1 inhibitor. HO-1 metabolites,
      bilirubin and CO, led to inhibit degranulation, and quercetin translocated Nrf2
      from cytoplasm into nucleus in RBL-2H3 cells. CONCLUSION: These results strongly
      suggest that quercetin exerted anti-allergic actions via activation of Nrf2-HO-1
      pathway.

PMID- 19390786
TI  - Enhancement of bone formation by genetically-engineered bone marrow stromal cells
      expressing BMP-2, VEGF and angiopoietin-1.
AB  - To explore the potential of combined delivery of osteogenic and angiogenic
      factors to bone marrow stromal cells (BMSCs) for repair of critical-size bone
      defects, we followed the formation of bone and vessels in tissue-engineered
      constructs in nude mice and rabbit bone defects upon introducing different
      combinations of BMP-2, vascular endothelial growth factor (VEGF) and angiopoietin
      1 (Ang-1) to BMSCs with adenoviral vectors. Better osteogenesis and angiogenesis
      were found in co-delivery group of BMP-2, VEGF and angiopoietin-1 than any other
      combination of these factors in both animal models, indicating combined gene
      delivery of angiopoietin-1 and VEGF165 into a tissue-engineered construct
      produces an additive effect on BMP-2-induced osteogenesis.

PMID- 19390784
TI  - The development and function of regulatory T cells.
AB  - Regulatory T cells (Tregs) are a critical subset of T cells that mediate
      peripheral tolerance. There are two types of Tregs: natural Tregs, which develop
      in the thymus, and induced Tregs, which are derived from naive CD4(+) T cells in
      the periphery. Tregs utilize a variety of mechanisms to suppress the immune
      response. While Tregs are critical for the peripheral maintenance of potential
      autoreactive T cells, they can also be detrimental by preventing effective anti
      tumor responses and sterilizing immunity against pathogens. In this review, we
      will discuss the development of natural and induced Tregs as well as the role of
      Tregs in a variety of disease settings and the mechanisms they utilize for
      suppression.

PMID- 19390787
TI  - Characterization of a mannose-6-phosphate isomerase from Geobacillus
      thermodenitrificans that converts monosaccharides.
AB  - A recombinant mannose-6-phosphate isomerase from Geobacillus thermodenitrificans
      (GTMpi) isomerizes aldose substrates possessing hydroxyl groups oriented in the
      same direction at the C2 and C3 positions such as the D- and L-forms of ribose,
      lyxose, talose, mannose, and allose. The activity of GTMpi for D-lyxose
      isomerization was optimal at pH 7.0, 70 degrees C and 1 mM Co(2+). Under these
      conditions, the k(cat) and K(m) values were 74,300 s(-1) and 390 mM for D-lyxose
      and 28,800 s(-1) and 470 mM for L-ribose, respectively. The half-lives of the
      enzyme at 60, 65, and 70 degrees C were 388, 73, and 27 h, respectively. GTMpi
      catalyzed the conversion of D-lyxose to D-xylulose with a 38% conversion yield
      after 3 h, and converted L-ribose to L-ribulose with a 29% conversion yield.

PMID- 19390788
TI  - Serum fluoride and sialic acid levels in osteosarcoma.
AB  - Osteosarcoma is a rare malignant bone tumor most commonly occurring in children
      and young adults presenting with painful swelling. Various etiological factors
      for osteosarcoma are ionizing radiation, family history of bone disorders and
      cancer, chemicals (fluoride, beryllium, and vinyl chloride), and viruses. Status
      of fluoride levels in serum of osteosarcoma is still not clear. Recent reports
      have indicated that there is a link between fluoride exposure and osteosarcoma.
      Glycoproteins and glycosaminoglycans are an integral part of bone and prolonged
      exposure to fluoride for long duration has been shown to cause degradation of
      collagen and ground substance in bones. The present study was planned to analyze
      serum fluoride, sialic acid, calcium, phosphorus, and alkaline phosphatase levels
      in 25 patients of osteosarcoma and age- and sex-matched subjects with bone
      forming tumours other than osteosarcoma and musculo-skeletal pain (controls, 25
      each). Fluoride levels were analyzed by ISE and sialic acid was analyzed by
      Warren's method. Mean serum fluoride concentration was found to be significantly
      higher in patients with osteosarcoma as compared to the other two groups. The
      mean value of flouride in patients with other bone-forming tumors was
      approximately 50% of the group of osteosarcoma; however, it was significantly
      higher when compared with patients of group I. Serum sialic acid concentration
      was found to be significantly raised in patients with osteosarcoma as well as in
      the group with other bone-forming tumors as compared to the group of controls.
      There was, however, no significant difference in the group of patients of
      osteosarcoma when compared with group of patients with other bone-forming tumors.
      These results showing higher level of fluoride with osteosarcoma compared to
      others suggesting a role of fluoride in the disease.

PMID- 19390789
TI  - Lead accumulation as possible risk factor for primary open-angle glaucoma.
AB  - We evaluated the association between hair lead concentrations and primary open
      angle glaucoma. Ninety-eight Japanese patients (40 males, 58 females; average age
      57.6 +/- 10.8 years) with primary open-angle glaucoma and control subjects (131
      males, 114 females; average age 56.0 +/- 12.8 years) were recruited in this
      study. Hair lead levels were measured by inductively coupled plasma mass
      spectrometry. Hair lead concentrations between primary open-angle glaucoma and
      control groups were compared using Mann-Whitney U test. As a subgroup analysis,
      we compared hair lead concentrations between low-tension glaucoma, high-tension
      glaucoma, and control groups using one-factor analysis of variance. Lead
      accumulation levels were significantly higher in the female subjects with primary
      open-angle glaucoma compared to the control group (P=0.03). Lead accumulation
      levels were significantly higher in female patients with low intraocular pressure
      compared to control group 2 (P=0.02). A higher hair lead level, which reflects
      the total body burden of lead, was observed to be associated with primary open
      angle glaucoma in females especially with low-tension glaucoma. Accumulation of
      lead may be an unrecognized risk factor of non-pressure-dependent glaucomatous
      optic neuropathy.

PMID- 19390790
TI  - Translating biomaterial properties to intracellular signaling.
AB  - Bioactive materials present important micro-environmental cues that induce
      specific intracellular signaling responses which ultimately determine cell
      behavior. For example, vascular endothelial cells on a normal vessel wall resist
      inflammation and thrombosis, but the same cells seeded on an artificial vascular
      graft or stent do not. What makes these cells behave so differently when they are
      adhered to different materials? Intracellular signaling from integrins and other
      cell-surface receptors is an important part of the answer, but these signaling
      responses constitute a highly-branched, interconnected network of molecules. In
      order to perform rational design of biomaterials, one must understand how
      altering the properties of the material (micro-environment) causes changes in
      cell behavior, and this in turn requires understanding the complex signaling
      response. Systems biology and mathematical modeling aid analysis of the
      connectivity of this network. This review summarizes applicable systems biology
      and mathematical modeling techniques including ordinary differential equations
      based models, principal component analysis, and Bayesian networks. Next covered
      is biomaterials research which studies the intracellular signaling responses
      generated by variation of biomaterial properties. Finally, the review details
      ways in which modeling has been or could be applied to better understand the link
      between biomaterial properties and intracellular signaling.

PMID- 19390791
TI  - Relationship of nutritional status with tuberculin sensitivity.
AB  - OBJECTIVE: To estimate the prevalence of under-nutrition among school children
      and to find out the relationship between nutritional status and tuberculin
      sensitivity. METHODS: A cross sectional study was carried out among 3335 children
      between 5-8 years of age attending 60 schools in Bangalore city selected by
      stratified random sampling. The nutritional anthropometric indices were
      calculated using reference median as recommended by World Health Organization,
      classified according to standard deviation units termed as Z-scores. The
      nutritional status of the children was assessed by Weight for age, Height for age
      and Bio-mass-index (BMI). RESULTS: Depending upon the method for classifying
      nutritional status, the prevalence of under-nutrition (including mild and severe
      under-nutrition) varied between 14.9-29.8%. The prevalence of severe under
      nutrition varied from 2.9-6.7%. The frequency distributions of reaction sizes
      were found to be similar among children classified by nutritional status. The
      differences in proportions of significant reactions (=10 mm) and mean tuberculin
      reaction sizes between children classified by nutritional status were not found
      to be statistically significant. CONCLUSION: Tuberculin sensitivity was not
      influenced by nutritional status among apparently healthy school children.

PMID- 19390792
TI  - A neonate with complete thrombosis of the aorta.

PMID- 19390793
TI  - Upper gastrointestinal bleeding in children in Southern Iran.
AB  - OBJECTIVE: To find out whether the causes of upper GI bleeding in our center in a
      developing country differed from developed countries. METHODS: Children
      presenting to our center with upper GI bleeding from March 2002 to March 2007,
      were retrospectively evaluated. Informations were retrieved from patient's
      history and physical examination and results of upper GI endoscopy regarding
      etiology of bleeding, managements, use of medications which might predispose
      patient to bleeding, and the mortality rate. RESULTS: From 118 children (67 boys;
      with age of 7.7+/-4.7 yrs) who underwent upper GI endoscopies, 50% presented with
      hematemesis, 14% had melena and 36% had both. The most common causes of upper GI
      bleeding among all patients were gastric erosions (28%), esophageal varices
      (16%), duodenal erosions (10%), gastric ulcer (8.5%), Mallory Weiss syndrome tear
      (7.8%), duodenal ulcer (6.8%), esophagitis (1.7%) and duodenal ulcer with gastric
      ulcer (0.8%). The causes of bleeding could not be ascertained in 20.5% of cases.
      No significant pre-medication or procedure related complications were observed.
      Endoscopic therapy was performed in 13.5% of patients. In 14.4% of patients,
      there was a history of consumption of medications predisposing them to upper GI
      bleeding. Two deaths occurred (1.7%) too. CONCLUSION: The findings in the present
      study showed that half of upper GI bleedings in pediatric patients from south of
      Iran, were due to gastric and duodenal erosions and ulcers. This study concludes
      that the causes of upper GI bleeding in children in our center of a developing
      country, are not different from those in developed ones.

PMID- 19390794
TI  - Factors affecting scholastic performances of adolescents.
AB  - OBJECTIVE: The present study aims at recognizing the social influence, study
      habits and health factors affecting scholastic performances of adolescents and to
      compare these factors among the adolescents between two categories of school.
      METHODS: A total of 1230 adolescents (13-18 yrs) were screened. Data was
      collected by personal interview, using the teenage screening questionnaire,
      Trivandrum, between May 2004 and November 2005. RESULTS: A total 615 students
      from corporation and private schools were studied. 39.76% (489) were high
      achievers, 13.5% (166) were low achievers with p < 0.001. In the low achievers,
      12.03% were from the corporation schools and 1.46% from private schools. The
      incidence of poor study habits and social factors were increased in low achievers
      of corporation schools. On multivariate analysis, the predictor variables for
      poor scholastic performance were adolescent having refractory error, not having
      help for study at home, not doing home work regularly, not solving question bank
      papers and reading only before examinations. CONCLUSION: It is feasible and
      worthwhile to identify the determinants of scholastic performance and plan
      intervention strategies at each school. The results of this study highlight the
      importance of implementing newer strategies, focusing on strict study patterns
      and creating the conducive school and home environment for study, so as to
      achieve better scholastic performances.

PMID- 19390795
TI  - Gliomatosis cerebri.
AB  - A 6-year-old boy who presented with worsening hemiplegia, behaviour problems and
      seizures after an episode of encephalitis-like illness is reported. MRI revealed
      diffuse signal change and swelling of the left cerebral hemisphere. The diagnosis
      of gliomatosis cerebri was confirmed by brain biopsy. Parents refused
      radiotherapy and the child worsened and died 6 months after diagnosis.

PMID- 19390796
TI  - Can Indian classical instrumental music reduce pain felt during venepuncture?
AB  - OBJECTIVE: Local anesthetic agent is not usually used to reduce pain experienced
      by children undergoing venepuncture. This study was undertaken to determine
      comparative efficacy of local anesthetic cream, Indian classical instrumental
      music and placebo, in reducing pain due to venepuncture in children. METHODS:
      Children aged 5-12 yr requiring venepuncture were enrolled in a prospective
      randomized clinical trial conducted at a tertiary care center. They were randomly
      assigned to 3 groups: local anesthetic (LA), music or placebo (control) group.
      Eutactic mixture of local anesthetic agents (EMLA) and Indian classical
      instrumental music (raaga-Todi) were used in the first 2 groups, respectively.
      Pain was assessed independently by parent, patient, investigator and an
      independent observer at the time of insertion of the cannula (0 min) and at 1-
      and 5 min after the insertion using a Visual Analog Scale (VAS). Kruskal- Wallis
      and Mann-Whitney U tests were used to assess the difference amongst the VAS
      scores. RESULTS: Fifty subjects were enrolled in each group. Significantly higher
      VAS scores were noted in control (placebo) group by all the categories of
      observers (parent, patient, investigator, independent observer) at all time
      points. The VAS scores obtained in LA group were lowest at all time points.
      However, the difference between VAS scores in LA group were significantly lower
      than those in music group only at some time-points and with some categories of
      observers (parent: 1 min; investigator: 0-, 1-, 5 min and independent observer: 5
      min). CONCLUSION: Pain experienced during venepuncture can be significantly
      reduced by using EMLA or Indian classical instrumental music. The difference
      between VAS scores with LA and music is not always significant. Hence, the choice
      between EMLA and music could be dictated by logistical factors.

PMID- 19390798
TI  - Plasmodium vivax malaria presenting with severe thrombocytopenia, cerebral
      complications and hydrocephalus.
AB  - Two cases of a one and 4 year old child of plasmodium vivax malaria are reported
      in association with CNS complications. Both presented with encephalopathy and
      seizures. One had severe thrombocytopenia, massive intracranial bleed and
      hydrocephalus requiring shunt surgery while the other had gastrointestinal
      manifestations, encephalopathy and hydrocephalus. Both responded to quinine but
      are left with sequelae.

PMID- 19390801
TI  - Congenital para esophageal hernia: a 10 year experience from Saudi Arabia.
AB  - OBJECTIVE: Para esophageal hiatal hernia is a rare childhood condition and
      reported series have had scant number of children which makes diagnosis a
      challenge. The authors sought to study the presentation and the outcome of
      treatment of congenital para esophageal hernias (CPEH) over a period of 10 years
      from a single tertiary care hospital in Saudi Arabia. METHODS: The records of 9
      patients presenting between 1997 and 2007, were retrospectively analyzed for
      demographics, presenting features, referral diagnoses, investigations, management
      including operative procedures, their outcome and follow-up. RESULTS: Nine
      patients (3 males and 6 females) aged between 8 days to 34 months were seen.
      Respiratory distress (n=6), vomiting (n=5) and frequent respiratory tract
      infections (n=3) were the most common presentations. Cyanosis (n=2), cough and
      excessive crying were the other important symptoms. The referral diagnoses in
      these patients included congenital Bochdalek's hernias, lung abscess,
      bronchogenic cyst, pneumatocoele, bronchiolitis, and pneumonias which reflected a
      misinterpretation of their clinical findings and chest X-rays. Seven of these
      patients had other associated congenital anomalies. Three had cardiovascular
      abnormalities and 2 had lesions of the central nervous system. A pair of siblings
      had Marfan's syndrome. All the patients had abnormal chest C-rays and an UGS
      (upper GI series) proved to be diagnostic in 8 patients. The CT scans done in 4
      patients corroborated the findings of the UGS. A laparotomy was done on most
      patients (n=8) which comprised of reduction of the stomach, resection of the
      hernial sac, tightening of the hiatus and a gastropexy or a gastrostomy. One
      patient, who underwent thoracotomy died of surgical complications. Two others
      died of causes unrelated to the surgery. The remaining six operated patients have
      been followed up for a median of 3.5 years and are doing well. CONCLUSION: CPEH
      is uncommon in children, presented with respiratory tract symptoms and vomiting,
      and may be associated with Martan's syndrome. It should be considered in the
      workup of a child with vomiting or frequent chest infections. Abnormal chest X
      rays may indicate the diagnosis and a subsequent UGS, is confirmatory. The
      present study found the aparotomya good approach for repair of the wide hiatus. A
      gastropexy and a floppy fundoplication were added to prevent reherniation and
      post operative reflux though given the small numbers it is not possible to
      determine the place of either of these procedures. CPEH may be frequently
      associated with other congenital problems which may impact survival.

PMID- 19390802
TI  - Utility of family studies in diagnosing abnormal hemoglobins/thalassemic states.
AB  - OBJECTIVE: To resolve all indeterminate cases on HPLC screening with the help of
      family studies and to further confirm the results by genetic analysis. METHODS:
      In our 11 years experience with HPLC at Sir Ganga Ram Hospital, we solved many
      cases with the help of family studies on parental blood samples in which patient
      could have possibly been homozygous vs compound heterozygous. Genetic analysis
      was done on index case as well as on parental samples with ARMS-PCR technique to
      confirm the results. RESULTS: In 100% of cases, we noted that the diagnosis
      obtained by family studies was commensurate with that obtained by DNA analysis.
      CONCLUSION: In centers, which do not have the facility for genetic analysis,
      family studies by HPLC can be equally useful.

PMID- 19390803
TI  - 'Glutaric aciduria type I--an easily diagnosable and treatable metabolic
      disorder'.

PMID- 19390806
TI  - Nutritional status of adolescent girls from an urban slum area in South India.
AB  - OBJECTIVE: To assess the nutritional status of adolescent girls in a slum
      community of Urban Health Center, Panangal. METHODS: A community-based cross
      sectional study was carried out over a period of two months. 223 adolescent girls
      of age 10-18 years were selected randomly. Data was collected by interviewing the
      adolescent girls using predesigned, pre tested, semi-structured schedule. Parents
      interview was taken whenever necessary. Anthropometric measurements were recorded
      using standardized methodology as recommended by World Health Organization (WHO).
      Standard operational definitions were used. Various statistical applications like
      percentiles, mean, standard deviation and proportions were used for analysis of
      the data. RESULTS: Overall prevalence of stunting was found to be 47% and 28.3%
      as per NCHS and Indian standards respectively. Prevalence of underweight was
      42.6% and 22.9% as per NCHS and Indian standards respectively. Prevalence of
      thinness was 20.6% as per Indian standards. CONCLUSION: It is concluded that
      there is a high prevalence of under nutrition among adolescent girls in this slum
      community. Health education and nutrition interventions are needed on priority
      basis.

PMID- 19390804
TI  - Endothelin-1 and leptin as markers of intrauterine growth restriction.
AB  - OBJECTIVE: To explore the role of endothelin-1 (ET-1) and leptin in intrauterine
      growth restriction (IUGR) among preeclamptic and non-pre-eclamptic women.
      METHODS: Forty three patients with a pregnancy complicated by IUGR, 23 cases with
      severe pre-eclampsia and 20 cases of non-pre-eclamptic were enrolled. Control
      group comprised 15 cases with uncomplicated pregnancy. Blood samples from
      umbilical artery and maternal venous blood were collected at the time of delivery
      for analysis of ET-1 and leptin levels. Mode of delivery, birth weight and Apgar
      score were also recorded. RESULTS: The mean maternal and fetal ET-1 level was
      significantly higher in pregnancies complicated by IUGR than in control group.
      The mean maternal leptin level was significantly higher in pre-eclamptic patients
      when compared to non-preeclamptic and control groups. Mean fetal leptin level was
      significantly lower in patients compared to control; however, when fetal leptin
      corrected to fetal weight, it was insignificantly different in the both groups. E
      mail: m. alhaggar@yahoo.co.uk. CONCLUSION: Maternal plasma ET-1 and leptin
      correlate with the degree of fetal growth restriction originating from
      deterioration of placental function. Maternal plasma leptin and ET-1 levels may
      reflect deterioration in fetal growth.

PMID- 19390807
TI  - Granulocytic sarcoma.
AB  - We present two cases where GS was sole presentations, months before the diagnosis
      of AML.

PMID- 19390808
TI  - Genotype/phenotype association in Indian congenital aniridia.
AB  - The developmental birth eye disorder of iris is known as aniridia. Heterozygous
      PAX6 gene, which causes human aniridia and small eye in mice, is located on
      chromosome 11p13. The variability had been documented between the affected
      individuals within the families, is due to genotypic variation.
      Haploinsufficiency renders PAX6 allele non-functional or amorphic, however it
      presents hypomorphic or neomorphic alleles. India is not a well-studied ethnic
      group, hence the focus on congenital aniridia gene analysis supports the
      literature and the phenotypic association were analysed both in sporadic as well
      as familial. The consistent association of truncating PAX6 mutations with the
      phenotype is owing to non-sense-mediated decay (NMD). It is presumed that the
      genetic impact of increased homozygosity and heterozygocity in Indian counter
      part arises as the consequence of consanguineous marriages. The real fact
      involved in congenital aniridia with other related phenotypes with PAX6 mutations
      are still controversial.

PMID- 19390810
TI  - Prevalence, correlates of and perceptions toward cigarette smoking among
      adolescents in South Korea.
AB  - OBJECTIVE: To estimate the prevalence of current smoking, correlates of smoking
      and assess exposure to and perceptions towards smoking by gender. METHODS: We
      used data from the South Korea Global Youth Tobacco Survey (GYTS). Frequencies of
      selected characteristics and their 95% confidence were obtained. Current
      cigarette smoking was defined as having smoked, even a single puff, within the
      last 30 days. Logistic regression analysis was conducted to assess the factors
      that were considered to be associated with current cigarette smoking in bivariate
      and multivariate analyses. RESULTS: Of the 5615 respondents, 7.4% males and 5.0%
      females reported being current smokers (p = 0.003). Having smoking friends was
      strongly associated with smoking after controlling for age, gender, parental
      smoking status, exposure to anti-smoking media messages, and perception of risks
      of smoking (OR=69.92; 95% CI [41.24, 118.57] for most friends and OR=11.86; 95%
      CI [7.26, 19.36] for some friends). Male gender and having one or both smoking
      parents were associated with smoking (OR=1.43; 95% CI [1.09, 1.89] and OR=1.29;
      95% CI [1.00-, 1.71] respectively). Exposure to antismoking media messages was
      negatively associated with smoking (OR=0.52; 95% CI [0.36, 0.77]. CONCLUSION:
      Prevalence of smoking among adolescents in South Korea is lower than in many
      other Asian countries. There is however, need to strengthen anti-tobacco messages
      especially among adolescents.

PMID- 19390811
TI  - Prevalence of emotional and behavioural problems among primary school children in
      Karachi, Pakistan--multi informant survey.
AB  - OBJECTIVE: To determine emotional and behavioural problem among school going
      children in Pakistan. METHODS: A cross sectional survey of school children of
      certain towns within Karachi metropolitan area, aged 5 to 11 years during 1(st)
      half of 2006. SDQ was filled out by parents and school teachers for the same
      children. Demographic data of parents, teachers and children were also collected
      using a separate performa. RESULTS: 7 private and 8 community schools agreed to
      participate. 1488 consent forms were sent to 700 parents of private school and
      788 parents of community school children. A total of 675 parents agreed to
      participate in the study. The response rate was 45.3%. Assessment of children's
      mental health was conducted using Strength and Difficulties Questionnaire (SDQ).
      Parents rated 34.4% of children as falling under the "abnormal category on SDQ,
      slightly higher estimates 35.8% were reported by the teacher. The findings
      suggest a striking difference between the informants' ratings as well as gender
      wise difference in prevalence of common child mental health problems. CONCLUSION:
      In the present study prevalence of child mental health problems was higher than
      reported in studies from other countries. There was also a gender difference in
      prevalence; boys had higher estimates of behavior/externalizing problems, whereas
      emotional problems were more common amongst females. There is a need for
      developing programs to train, sensitise and mobilize teachers and parents
      regarding child's psychological, emotional and behavioral problems.

PMID- 19390812
TI  - Client satisfaction with immunization services in urban slums of Lucknow
      district.
AB  - OBJECTIVE: To assess the satisfaction of parents with the immunization services
      and its association with their sociodemographic characteristics. METHODS: The
      study was a part of the coverage evaluation survey conducted using the WHO 30
      cluster sampling methodology in the Urban slums of Lucknow district, north India.
      Analysis for a total of 388 respondents of completely or partially immunized
      children, was done to assess the level of satisfaction and its determinants.
      RESULTS: The overall satisfaction was more than 90% in the respondents of both
      the categories of the children, however the difference between the satisfaction
      rates was found to be significant. Also the satisfaction with accessibility
      (p<0.04) and information given by the health worker (p<0.00) differed
      significantly between completely and partially immunized. Most of the
      sociodemographic factors were not found to have a significant association with
      the satisfaction related to different parameters of the immunization services.
      CONCLUSION: The dissatisfaction regarding the various aspects of immunization
      services emphasizes the imperative need to take urgent intervention, for the
      achievement of goal of universal immunization.

PMID- 19390813
TI  - Evaluation of the cases with acute disseminated encephalomyelitis.
AB  - OBJECTIVE: We aimed to describe the epidemiologic, clinical, laboratory features,
      neuroimaging, treatment, and outcome of children with acute disseminated
      encephalomyelitis in a cohort study. METHODS: In this study, twelve children who
      were diagnosed as acute disseminated encephalomyelitis were reviewed
      retrospectively. All of the cases were reevaluated with systemic and neurological
      examinations, serologic tests, cerebrospinal fluid investigations, magnetic
      resonance imaging. RESULT: Their age ranged between 2.5 and 16 years. Five of the
      cases had initial infections. Patients presented most often with motor deficits
      (75%), secondly with loss of conscious (33%), and seizures (33%). Spinal fluid
      abnormalities occurred in 41.6%. Cranial, and spinal magnetic resonance imaging
      (MRI) revealed hyperintense signal changes mainly in basal ganglia and thalamus
      (58%), cortical and subcortical areas (33) in T2 weighted images. Myelitis was
      determined in two cases. Six patients were treated with steroid, and 3 were
      treated with intravenous immunoglobulin. Ten patients recovered completely. We
      observed relapse in one case and recurrence in two cases. These cases responded
      well to high dose intravenous prednisolone followed by oral prednisolone for 6
      months. CONCLUSION: Outlook recovery is generally good in acute disseminated
      encephalomyelitis. Recurrence and neurological deficits are rarely seen. Early
      treatment of prednisolone is one of the most important factors to determine the
      prognosis in this disease.

PMID- 19390814
TI  - Benefit of urinalysis.
AB  - OBJECTIVE: In the pilot Iran school screening programme, the minimal cost of
      screening dipstick urinalysis in 1601 asymptomatic school children was
      determined. METHODS: The cost of screening dipstick urinalysis was calculated by
      reviewing the literature for the prevalence of asymptomatic proteinuria,
      hematuria, bacteriuria, and glucosuria determined by an initial dipstick
      urinalysis. The minimal cost utilizing data of 3 general physicians was
      calculated. Costs were determined by using current charge for supplies ordered to
      perform tests, charges for tests performed by a commercial laboratory, and the
      cost of a final evaluation by a pediatric nephrologist. RESULTS: 4.7% (76/1601)
      of patients were calculated to have an initial abnormal urinalysis. Upon
      retesting 1.37% (22/1601) of patients were calculated to have a persistent
      abnormality. The calculated cost was $167 to initially screen all 1601 patients
      with a dipstick urinalysis or $0.092 per patient. The calculated cost to
      evaluates the 22 patients with any persistent abnormality on repeat dipstick
      urinalysis was $0.02 or $0.001 per patient. This is the calculated cost for a
      single screening of 1601 asymptomatic pediatric patients. CONCLUSION: Multiple
      screening dipstick urinalysis in asymptomatic pediatric is costly and should be
      discontinued. We propose that a single screening dipstick urinalysis be obtained
      at school entry age, between 6 and 7 years, in all asymptomatic children.

PMID- 19390815
TI  - Does prophylactic use of dexamethasone have a role in reducing post extubation
      stridor and reintubation in children?
AB  - All children aged from 4 weeks to <5 year, were intubated for at least 48 hours
      [n=51] during 6 months. Data of the patients treated with DEX (0.5 ml/kg every 6
      hours for 3 doses, beginning 6-12 hours prior to extubation) (n=30) were compared
      with control patients (who had not received medication) (n=21). The DEX and
      control groups were similar in age i.e., mean ages of DEX group were 16.85+/-14
      months, and that of control group were 19.02 +/- 19 months, mean duration of
      intubation and mechanical ventilation in DEX group was 5.17 +/- 4.58 days, and
      that in control group was 3.98 +/- 3.60 days. There was no significant difference
      between DEX and control group in the incidence of postextubation stridor [17%
      (5/30) vs. 10% (2/21); p = 0.5] and the reintubation rate [7% (2/30) vs. 10%
      (2/21); p = 0.7]. Our data revealed that the prophylactic use of dexamethasone in
      planned extubation of high risk children were not effective.

PMID- 19390816
TI  - Efficacy of a low cost protocol in reducing noise levels in the neonatal
      intensive care unit.
AB  - OBJECTIVE: To examine the effectiveness and cost of implementing a noise
      reduction protocol in a level III neonatal intensive care unit (NICU). METHODS: A
      prospective longitudinal study was done in a level III NICU, wherein a noise
      reduction protocol that included behavioral and environmental modification was
      implemented. The noise levels were measured sequentially every hour for 15 days
      before and after this intervention. The statistical significance of the reduction
      in noise levels after implementation of the protocol was tested by paired sample
      student's t-test. Cost was calculated using the generalized cost effectiveness
      model of the World Health Organisation. The present study has 80% power with 95%
      confidence to measure 2 dB differences between groups for the maximum recommended
      of 50 dB. RESULTS: The protocol in the present study reduced noise levels in all
      the rooms of the NICU to within 60 dB with high statistical significance (p<
      0.001). The extent of noise reduction in the rooms of the NICU was as follows:
      ventilator room by 9.58 dB (95% confidence interval: 6.73-12.42, p < 0.001),
      stable room by 6.54 dB (95% confidence interval: 2.92-4.16, p < 0.001), isolation
      room by 2.26 dB (95% confidence interval: 1.21-3.30, p < 0.001), pre-term room by
      2.37 dB(95% confidence interval: 1.22-3.51, p < 0.001) and extreme preterm room
      by 2.09 dB (95% confidence interval: 1.14-3.02, p < 0.001). The intervention was
      most cost-effective in the ventilator room, requiring Rs. 81.09 to reduce 1 dB
      and least effective in the extreme pre-term room requiring Rs. 371.61 to reduce 1
      dB. CONCLUSION: The high efficacy and affordability of noise reduction protocols
      justify the need for implementation of these measures as a standard of care in
      neonatal intensive care units.

PMID- 19390817
TI  - Yale Observation Scale for prediction of bacteremia in febrile children.
AB  - OBJECTIVE: To assess the accuracy and reliability of Yale Observation Scale (YOS)
      predicting bacteremia. METHODS: 219 consecutive febrile inpatients aged 3-36
      months were the subjects. Before giving antipyretics, rectal temperature was
      recorded. YOS scores were assessed by 2 independent blinded residents. History,
      clinical examination and investigations followed. Blood cultures were taken in
      all children before antibiotics. Point estimates and 95% confidence intervals
      were calculated for sensitivity, specificity, positive & negative predictive
      values and likelihood ratios for use of YOS as a diagnostic test in prediction of
      bacteremia. The best cut off value for a positive YOS test was established by
      calculating these statistical values separately for a cut off YOS score of 8, 10
      and 12 and plotting ROC curve. Reliability of YOS was assessed by the inter
      observer agreement through kappa statistics. RESULTS: Study population (n=219)
      had 59.36% males and a mean age of 15.24 months. 28.16% subjects had bacteremia.
      Mean YOS scores were significantly higher in bacteremic children (14.9 vs 8.78 in
      non-bacteremic, p=0.00001) Sensitivity, specificity, PPV, NPV, LR+ and LR- of YOS
      score >10 to predict bacteremia were 87.93%, 83.78%, 68.00%, 94.66%, 5.42 and
      0.14 respectively. Those of YOS score >8 were 96.55%, 65.54%, 52.34%, 97.98%,
      2.80 and 0.05 respectively and of a YOS score >12 were 48.28%, 91.22%, 68.29%,
      81.82%, 5.5 and 0.5 respectively. ROC curve showed YOS score >10 to be the best
      cut off for prediction of bacteremia. Area under ROC curve was 0.9001. The chance
      corrected inter-observer agreement (kappa) was 0.7919. CONCLUSION: YOS is a
      simple, easy to administer, cost-effective and useful test to predict bacteremia
      in a febrile child aged 3-36 months due to its high sensitivity and
      reproducibility.

PMID- 19390818
TI  - Use of DNA-specific anthraquinone dyes to directly reveal cytoplasmic and nuclear
      boundaries in live and fixed cells.
AB  - Image-based, high-content screening assays demand solutions for image
      segmentation and cellular compartment encoding to track critical events--for
      example those reported by GFP fusions within mitosis, signalling pathways and
      protein translocations. To meet this need, a series of nuclear/cytoplasmic
      discriminating probes have been developed: DRAQ5 and CyTRAK Orange. These are
      spectrally compatible with GFP reporters offering new solutions in imaging and
      cytometry. At their most fundamental they provide a convenient fluorescent
      emission signature which is spectrally separated from the commonly used reporter
      proteins (e.g. eGFP, YFP, mRFP) and fluorescent tags such as Alexafluor 488,
      fluorescein and Cy2. Additionally, they do not excite in the UV and thus avoid
      the complications of compound UV-autofluorescence in drug discovery whilst
      limiting the impact of background sample autofluorescence. They provide a
      convenient means of stoichiometrically labelling cell nuclei in live cells
      without the aid of DMSO and can equally be used for fixed cells. Further
      developments have permitted the simultaneous and differential labelling of both
      nuclear and cytoplasmic compartments in live and fixed cells to clearly render
      the precise location of cell boundaries which may be beneficial for quantitative
      expression measurements, cell-cell interactions and most recently compound in
      vitro toxicology testing.

PMID- 19390819
TI  - Olig2 transcription factor in the developing and injured forebrain; cell lineage
      and glial development.
AB  - Olig2 transcription factor is widely expressed throughout the central nervous
      system; therefore, it is considered to have multiple functions in the developing,
      mature and injured brain. In this mini-review, we focus on Olig2 in the forebrain
      (telencephalon and diencephalon) and discuss the functional significance of Olig2
      and the differentiation properties of Olig2-expressing progenitors in the
      development and injured states. Short- and long-term lineage analysis in the
      developing forebrain elucidated that not all late Olig2+ cells are direct cohorts
      of early cells and that Olig2 lineage cells differentiate into neurons or glial
      cells in a region- and stage-dependent manner. Olig2-deficient mice revealed
      large elimination of oligodendrocyte precursor cells and a decreased number of
      astrocyte progenitors in the dorsal cortex, whereas no reduction in the number of
      GABAergic neurons. In addition to Olig2 function in the developing cortex, Olig2
      is also reported to be important for glial scar formation after injury. Thus,
      Olig2 can be essential for glial differentiation during development and after
      injury.

PMID- 19390820
TI  - Leukotriene B4 regulates proliferation and differentiation of cultured rat
      myoblasts via the BLT1 pathway.
AB  - Skeletal muscle regeneration is a highly orchestrated process initiated by
      activation of adult muscle satellite cells. Upon muscle injury, the inflammatory
      process is always accompanied by muscle regeneration. Leukotriene B(4) is one of
      the essential inflammatory mediators. We isolated and cultured primary satellite
      cells. RT-PCR showed that myoblasts expressed mRNA for LTB(4) receptors BLT1 and
      BLT2, and LTB4 promoted myoblast proliferation and fusion. Quantitative real-time
      PCR and immunoblotting showed that LTB(4) treatment expedited the expression
      process of differentiation markers MyoD and M-cadherin. U-75302, a specific BLT1
      inhibitor, but not LY2552833, a specific BLT2 inhibitor, blocked proliferation
      and differentiation of myoblasts induced by LTB(4), which implies the involvement
      of the BLT1 pathway. Overall, the data suggest that LTB(4) contributes to muscle
      regeneration by accelerating proliferation and differentiation of satellite
      cells.

PMID- 19390821
TI  - An ARIA-interacting AP2 domain protein is a novel component of ABA signaling.
AB  - ADAP is an AP2-domain protein that interacts with ARIA, which, in turn, interacts
      with ABF2, a bZIP class transcription factor. ABF2 regulates various aspects of
      the abscisic acid (ABA) response by controlling the expression of a subset of ABA
      responsive genes. Our expression analyses indicate that ADAP is expressed in
      roots, emerging young leaves, and flowers. We found that adap knockout mutant
      lines germinate more efficiently than wild-type plants and that the mutant
      seedlings grow faster. This suggests that ADAP is involved in the regulation of
      germination and seedling growth. Both germination and post-germination growth of
      the knockout mutants were partially insensitive to ABA, which indicates that ADAP
      is required for a full ABA response. The survival rates for mutants from which
      water was withheld were low compared with those for wild-type plants. The result
      shows that ADAP is necessary for the response to stress induced by water
      deprivation. Together, our data indicate that ADAP is a positive regulator of the
      ABA response and is also involved in regulating seedling growth. The role of ADAP
      is similar to that of ARIA, which is also a positive regulator of the ABA
      response. It appears that ADAP acts through the same ABA response pathway as
      ARIA.

PMID- 19390822
TI  - Lipoxygenase inhibitors suppressed carrageenan-induced Fos-expression and
      inflammatory pain responses in the rat.
AB  - Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is
      unclear whether the inhibition of the LO activity regulates the expression of c
      Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced
      inflammation model to examine the role of LO in the development of c-Fos
      expression. Intradermally injected carrageenan caused elevated number of cells
      exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and
      decreased the thermal and mechanical threshold in Hargreaves and von Frey tests.
      Pretreatment with an inhibitor of phospholipase A2, that generates the LO
      substrate, prior to the carrageenan injection significantly reduced the number of
      Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO
      inhibitor baicalein also exhibited the similar effects. Moreover, the LO
      inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic
      behaviors, which inidcates that the changes in Fos expression correlates with
      those in the nociceptive behaviors in the inflamed rats. LO products are
      endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist
      inhibited the thermal but not the mechanical hypersensitivity. Overall, our
      results from the Fos-LI and behavior tests suggest that LO products released from
      inflamed tissues contribute to nociception during carrageenan-induced
      inflammation, indicating that the LO pathway is a possible target for modulating
      inflammatory pain.

PMID- 19390823
TI  - Molecular cloning and expression of a Cu/Zn-Containing superoxide dismutase from
      Thellungiella halophila.
AB  - Superoxide dismutases (SODs) constitute the first line of cellular defense
      against oxidative stress in plants. SODs generally occur in three different forms
      with Cu/Zn, Fe, or Mn as prosthetic metals. We cloned the full-length cDNA of the
      Thellungiella halophila Cu/Zn-SOD gene ThCSD using degenerate RT-PCR and rapid
      amplification of cDNA ends (RACE). Sequence analysis indicated that the ThCSD
      gene (GenBank accession number EF405867) had an open reading frame of 456 bp. The
      deduced 152-amino acid polypeptide had a predicted molecular weight of 15.1 kDa,
      an estimated pI of 5.4, and a putative Cu/Zn-binding site. Recombinant ThCSD
      protein was expressed in Escherichia coli and assayed for SOD enzymatic activity
      in a native polyacrylamide gel. The SOD activity of ThCSD was inactivated by
      potassium cyanide and hydrogen peroxide but not by sodium azide, confirming that
      ThCSD is a Cu/Zn-SOD. Northern blotting demonstrated that ThCSD is expressed in
      roots, stems, and leaves. ThCSD mRNA levels increased by about 30-fold when
      plants were treated with sodium chloride (NaCl), abscisic acid (ABA), and indole
      acetic acid (IAA) and by about 50-fold when treated with UVB light. These results
      indicate that ThCSD is involved in physiological pathways activated by a variety
      of environmental conditions.

PMID- 19390824
TI  - Complete mitochondrial genome sequence of the yellow-spotted long-horned beetle
      Psacothea hilaris (Coleoptera: Cerambycidae) and phylogenetic analysis among
      coleopteran insects.
AB  - We have determined the complete mitochondrial genome of the yellow-spotted long
      horned beetle, Psacothea hilaris (Coleoptera: Cerambycidae), an endangered insect
      species in Korea. The 15,856-bp long P. hilaris mitogenome harbors gene content
      typical of the animal mitogenome and a gene arrangement identical to the most
      common type found in insect mitogenomes. As with all other sequenced coleopteran
      species, the 5-bp long TAGTA motif was also detected in the intergenic space
      sequence located between tRNA(Ser)(UCN) and ND1 of P. hilaris. The 1,190-bp long
      non-coding A+T-rich region harbors an unusual series of seven identical repeat
      sequences of 57-bp in length and several stretches of sequences with the
      potential to form stem-and-loop structures. Furthermore, it contains one
      tRNA(Arg)-like sequence and one tRNA(Lys)-like sequence. Phylogenetic analysis
      among available coleopteran mitogenomes using the concatenated amino acid
      sequences of PCGs appear to support the sister group relationship of the suborder
      Polyphaga to all remaining suborders, including Adephaga, Myxophaga, and
      Archostemata. Among the two available infraorders in Polyphaga, a monophyletic
      Cucujiformia was confirmed, with the placement of Cleroidea as the basal lineage
      for Cucujiformia. On the other hand, the infraorder Elateriformia was not
      identified as monophyletic, thereby indicating that Scirtoidea and Buprestoidea
      are the basal lineages for Cucujiformia and the remaining Elateriformia.

PMID- 19390825
TI  - Chromatin structural rearrangement during dedifferentiation of protoplasts of
      Cucumis sativus L.
AB  - This paper reports on the structural rearrangement of satellite DNA type I
      repeats and heterochromatin during the dedifferentiation and cell cycling of
      mesophyll protoplasts of cucumber (Cucumis sativus). These repeats were localized
      in the telomeric heterochromatin of cucumber chromosomes and in the chromocenters
      of interphase nuclei. The dramatic reduction of heterochromatin involves
      decondensation of subtelomeric repeats in freshly isolated protoplasts; however,
      there are not a great many remarkable changes in the expression profile. In spite
      of that, reformation of the chromocenters, occurring 48 h after protoplast
      isolation, is accompanied by recondensation of satellite DNA type I; however,
      only partial reassembly of these repeats was revealed. In this study, FISH and a
      flow cytometry assay show a correlation between the partial chromocenter and the
      repeats reassembly, and with the reentry of cultivated protoplasts into the cell
      cycle and first cell division. After that, divided cells displayed a higher
      variability in the expression profile than did leaves' mesophyll cells and
      protoplasts.

PMID- 19390826
TI  - Ectopic expression of a cold-responsive OsAsr1 cDNA gives enhanced cold tolerance
      in transgenic rice plants.
AB  - The OsAsrt cDNA clone was isolated from a cDNA library prepared from developing
      seed coats of rice (Oryza sativa L.). Low-temperature stress increased mRNA
      levels of OsAsr1 in both vegetative and reproductive organs. In situ analysis
      showed that OsAsr1 transcript was preferentially accumulated in the leaf
      mesophyll tissues and parenchyma cells of the palea and lemma. For transgenic
      rice plants that over-expressed full-length OsAsr1 cDNA in the sense orientation,
      the Fv/Fm values for photosynthetic efficiency were about 2-fold higher than
      those of wild type-segregating plants after a 24-h cold treatment. Seedlings
      exposed to prolonged low temperatures were more tolerant of cold stress, as
      demonstrated during wilting and regrowth tests. Interestingly, OsAsr1 was highly
      expressed in transgenic rice plants expressing the C-repeat/dehyhdration
      responsive element binding factor 1 (CBF1), suggesting the regulation of OsAsr1
      by CBF1. Taken together, we suggest that OsAsr1 gene play an important role
      during temperature stress, and that this gene can be used for generating plants
      with enhanced cold tolerance.

PMID- 19390827
TI  - Sequence diversity of a domesticated transposase gene, MUG1, in Oryza species.
AB  - MUG1 is a MULE transposon-related domesticated gene in plants. We assessed the
      sequence diversity, neutrality, expression, and phylogenetics of the MUG1 gene
      among Oryza ssp. We found MUG1 expression in all tissues analyzed, with different
      levels in O. sativa. There were 408 variation sites in the 3886 bp of MUG1 locus.
      The nucleotide diversity of the MUG1 was higher than functionally known genes in
      rice. The nucleotide diversity (pi) in the domains was lower than the average
      nucleotide diversity in whole coding region. The pi values in nonsynonymous sites
      were lower than those of synonymous sites. Tajima D and Fu and Li D* values were
      mostly negative values, suggesting purifying selection in MUG1 sequences of Oryza
      ssp. Genome-specific variation and phylogenetic analyses show a general grouping
      of MUG1 sequences congruent with Oryza ssp. biogeography; however, our MUG1
      phylogenetic results, in combination with separate B and D genome studies, might
      suggest an early divergence of the Oryza ssp. by continental drift of
      Gondwanaland. O. longistaminata MUG1 divergence from other AA diploids suggests
      that it might not be a direct ancestor of the African rice species.

PMID- 19390828
TI  - Identification and characterization of alternative promoters of the rice MAP
      kinase gene OsBWMK1.
AB  - Our previous study suggested that OsBWMK1, a gene which encodes a member of the
      rice MAP kinase family, generates transcript variants which show distinct
      expression patterns in response to environmental stresses. The transcript
      variants are generated by alternative splicing and by use of alternative
      promoters. To test whether the two alternative promoters, pOsBWMK1L (promoter for
      the OsBWMK1L splice variant) and pOsBWMK1S (promoter for the OsBWMK1S splice
      variant), are biologically functional, we analyzed transgenic plants expressing
      GUS fusion constructs for each promoter. Both pOsBWMK1L and pOsBWMK1S are
      biologically active, although the activity of pOsBWMK1S is lower than that of
      pOsBWMK1L. Histochemical analysis revealed that pOsBWMK1L is constitutively
      active in most tissues at various developmental stages in rice and Arabidopsis,
      whereas pOsBWMK1S activity is spatially and temporally restricted. Furthermore,
      the expression of pOsBWMK1S::GUS was upregulated in response to hydrogen
      peroxide, a plant defense signaling molecule, in both plant species. These
      results suggest that the differential expression of OsBWMK1 splice variants is
      the result of alternative promoter usage and, moreover, that the mechanisms
      controlling OsBWMK1 gene expression are conserved in both monocot and dicot
      plants.

PMID- 19390829
TI  - Functional analysis of the stress-inducible soybean calmodulin isoform-4 (GmCaM
      4) promoter in transgenic tobacco plants.
AB  - The transcription of soybean (Glycine max) calmodulin isoform-4 (GmCaM-4) is
      dramatically induced within 0.5 h of exposure to pathogen or NaCl. Core cis
      acting elements that regulate the expression of the GmCaM-4 gene in response to
      pathogen and salt stress were previously identified, between -1,207 and -1,128
      bp, and between -858 and -728 bp, in the GmCaM-4 promoter. Here, we characterized
      the properties of the DNA-binding complexes that form at the two core cis-acting
      elements of the GmCaM-4 promoter in pathogen-treated nuclear extracts. We
      generated GUS reporter constructs harboring various deletions of approximately
      1.3-kb GmCaM-4 promoter, and analyzed GUS expression in tobacco plants
      transformed with these constructs. The GUS expression analysis suggested that the
      two previously identified core regions are involved in inducing GmCaM-4
      expression in the heterologous system. Finally, a transient expression assay of
      Arabidopsis protoplasts showed that the GmCaM-4 promoter produced greater levels
      of GUS activity than did the CaMV35S promoter after pathogen or NaCl treatments,
      suggesting that the GmCaM-4 promoter may be useful in the production of
      conditional gene expression systems.

PMID- 19390830
TI  - Temporal and spatial expression patterns of nine Arabidopsis genes encoding
      Jumonji C-domain proteins.
AB  - Diverse posttranslational modifications of histones, such as acetylation and
      methylation, play important roles in controlling gene expression. Histone
      methylation in particular is involved in a broad range of biological processes,
      including heterochromatin formation, X-chromosome inactivation, genomic
      imprinting, and transcriptional regulation. Recently, it has been demonstrated
      that proteins containing the Jumonji (Jmj) C domain can demethylate histones. In
      Arabidopsis, twenty-one genes encode JmjC domain-containing proteins, which can
      be clustered into five clades. To address the biological roles of the Arabidopsis
      genes encoding JmjC-domain proteins, we analyzed the temporal and spatial
      expression patterns of nine genes. RT-PCR analyses indicate all nine Arabidopsis
      thaliana Jmj (AtJmj) genes studied are actively expressed in various tissues.
      Furthermore, studies of transgenic plants harboring AtJmj::beta-glucuronidase
      fusion constructs reveal that these nine AtJmj genes are expressed in a
      developmentally and spatially regulated manner.

PMID- 19390831
TI  - Every single cell clones from cancer cell lines growing tumors in vivo may not
      invalidate the cancer stem cell concept.
AB  - We present the result of our research on the tumorigenic ability of single cell
      clones isolated from an aggressive murine breast cancer cell line in a matched
      allografting mouse model. Tumor formation is basically dependent on the cell
      numbers injected per location. We argue that in vivo tumor formation from single
      cell clones, isolated in vivo from cancer cell lines, may not provide conclusive
      evidence to disprove the cancer stem cell (CSC) theory without additional data.

PMID- 19390832
TI  - Backbone resonance assignment of a proteolysis-resistant fragment in the oxygen
      dependent degradation domain of the hypoxia inducible factor 1alpha.
AB  - Hypoxia-inducible factor 1alpha (HIF1alpha) is a transcription factor that plays
      a key role in the adaptation of cells to low oxygen stress and oxygen
      homeostasis. The oxygen-dependent degradation (ODD) domain of HIF1alpha
      responsible for the negative regulation of HIF1alpha in normoxia is intrinsically
      unfolded. Here, we carried out the backbone (1)H, (15)N, and (13)C resonance
      assignment of a proteolysis-resistant fragment (residues 404-477) in the
      HIF1alpha ODD domain using NMR spectroscopy. About 98% (344/352) of all the
      (1)HN, (15)N, (13)Calpha, (13)Cbeta, and (13)CO resonances were unambiguously
      assigned. The results will be useful for further investigation of the structural
      and dynamic states of the HIF1alpha ODD domain and its interaction with binding
      partners.

PMID- 19390833
TI  - [Clinical and experimental considerations for evaluation of Eustachian tube
      physiology].
AB  - BACKGROUND: Eustachian tube dysfunction plays a pivotal role in the pathogenesis
      of otitis media with effusion. Besides the lack of sufficient animal models to
      investigate the role of gastroesophageal reflux on Eustachian tube function,
      there is no reliable test that clinically allows the quantification of Eustachian
      tube function. Therefore, we established a Mongolian gerbil model to trace
      gastroesophageal reflux into the middle ear. In gerbils with traceable reflux,
      the refluxate reached the both middle ears through the Eustachian tubes in most
      cases. METHODS: Clinical studies were performed to analyze the reproducibility of
      measuring the accuracy of modified tube manometry in healthy Caucasians. RESULTS:
      Tube manometry was found to be a reliable and reproducible tool for measuring
      Eustachian tube function. CONCLUSIONS: Both our animal model and the clinical
      application of tube manometry are likely to be useful for further experimental
      and clinical studies.

PMID- 19390834
TI  - [The birth of ENT happened in Rostock].

PMID- 19390835
TI  - [Pancreas and islet transplantation].
AB  - Pancreas transplantation is a successful and effective procedure resulting in
      tight glucose control. Due to the postoperative morbidity and the need for
      immunosuppression pancreas transplantation should be considered in patients with
      type I diabetes at the time of kidney transplantation. Besides this pancreas
      transplantation alone can be taken into consideration for patients with very poor
      metabolic control and quality of life despite optimal medical treatment.
      Recently, islet transplantation became a less invasive alternative to pancreas
      transplantation. Due to the lack of long-term follow-up and due to the need of
      multiple donor grafts for one recipient, islet transplantation should be
      performed under experimental settings in experienced centers. New developments in
      protecting transplanted islets and in the induction of donor-specific tolerance
      could increase the indication to perform the procedure. Therefore alternative
      sources of beta-cells have to be identified.

PMID- 19390836
TI  - Siglec receptors and hiding plaques in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease. One hallmark
      of this disease is the continuous increase in the numbers and size of aggregating
      amyloid plaques. The accumulation of extracellular plaques is an immunologically
      interesting phenomenon since microglial cells, brain-specific macrophages, should
      be able to cleanse the aggregating material from the human brain. Immunotherapy
      targeting beta-amyloid peptides in plaques with antibodies represents a promising
      therapy in AD. Recent progress in pattern recognition receptors of monocytes and
      macrophages has revealed that the sialic acid-binding, immunoglobulin-like lectin
      (Siglec) family of receptors is an important recognition receptor for sialylated
      glycoproteins and glycolipids. Interestingly, recent studies have revealed that
      microglial cells contain only one type of Siglec receptors, Siglec-11, which
      mediates immunosuppressive signals and thus inhibits the function of other
      microglial pattern recognition receptors, such as TLRs, NLRs, and RAGE receptors.
      We will review here the recent literature which clearly indicates that
      aggregating amyloid plaques are masked in AD by sialylated glycoproteins and
      gangliosides. Sialylation and glycosylation of plaques, mimicking the cell
      surface glycocalyx, can activate the immunosuppressive Siglec-11 receptors, as
      well as hiding the neuritic plaques, allowing them to evade the immune
      surveillance of microglial cells. This kind of immune evasion can prevent the
      microglial cleansing process of aggregating amyloid plaques in AD.

PMID- 19390837
TI  - [Management of complications after sling and mesh implantations].
AB  - Tension-free alloplastic slings (TFAS) have revolutionized surgery for female
      stress urinary incontinence for more than 15 years. The procedure is easy to
      perform, minimally invasive with short operation time in an ambulatory setting,
      and has proven efficacy comparable to the gold standard procedure of retropubic
      colposuspension.Possible TFAS complications are potentially underestimated with
      respect to prevalence and manageability. We report our experience with major
      complications following TFAS and mesh implantation in patients referred to our
      interdisciplinary continence center. Patient history, risk factors, and
      preoperative diagnostics were analyzed for development of individualized
      treatment strategies. Overcorrections with formation of postvoid residual (PVR)
      can occur in retropubic TFAS as well as in transobturator TFAS. However, the most
      prevalent and challenging complication is de novo urgency. Major complications
      like urethrovaginal fistula, sling arrosions of the urethra, bladder, and vagina
      as well as infected gangrene and complete urethral loss requiring urinary
      diversion were seen at a frequency suggesting underrepresentation of these
      complications in the literature. The large amount of implanted artificial mesh
      material used for pelvic organ prolapse (POP) correction represents a particular
      challenge in cases of dyspareunia or persisting pelvic pain.Complication
      management has to be based on cystoscopic, urodynamic, and physical examination
      findings to be individualized to each patient and must take potential risks of
      recurrent incontinence or persisting complaints into account.To prevent TFAS or
      mesh complications, every patient should have tried all conservative treatment
      options and should be completely evaluated (including urodynamics)
      preoperatively. Artificial meshes should only be used in cases of prolapse
      recurrence or in otherwise inoperable patients. Postoperative urodynamics may
      help to document treatment success and to identify and quantify complications.

PMID- 19390838
TI  - Dissection of the factors affecting development-controlled and race-specific
      disease resistance conferred by leucine-rich repeat receptor kinase-type R genes
      in rice.
AB  - Development-controlled resistance and resistance specificity frequently restrict
      the application of a disease resistance (R) gene in crop breeding programs.
      Xa3/Xa26 and Xa21, encoding leucine-rich repeat (LRR)-kinase type plasma membrane
      proteins, mediate race-specific resistance to Xanthomonas oryzae pv. oryzae
      (Xoo), which causes bacterial blight, one of the most devastating rice diseases.
      Plants carrying Xa3/Xa26 and plants carrying Xa21 have different resistance
      spectra and the functions of the two R genes are regulated by developmental
      stage. Four chimeric genes encoding proteins consisting of different parts of
      XA3/XA26 and XA21 were constructed by domain swapping and transformed into a
      susceptible rice variety. The resistance spectra and development-regulated
      resistance of the transgenic plants carrying Xa3/Xa26, Xa21, or chimeric gene to
      different Xoo strains were analyzed in the same genetic background. The results
      suggest that the gradually increased expression of Xa3/Xa26 and Xa21 plays an
      important role in the progressively enhanced Xoo resistance during rice
      development. In addition, the LRR domains of XA3/XA26 and XA21 are important
      determinants of race-specific recognition during rice-Xoo interaction, but
      juxtamembrane regions of the two R proteins also appear to contribute to
      resistance specificity.

PMID- 19390839
TI  - Characterization of chsA, a new gene controlling the chemotactic response in
      Azospirillum brasilense Sp7.
AB  - We report, here, the characterization of a mutant strain of Azospirillum
      brasilense Sp7 impaired in surface motility and chemotactic response. Presence of
      flagella in the mutant strain was confirmed by western blot analysis, using
      antisera raised against the polar and lateral flagellins, and by electron
      microscopy. Genetic complementation and nucleotide sequencing led to the
      identification of a new gene, named chsA. The deduced translation product, ChsA
      protein, contained a PAS sensory domain and an EAL domain. As ChsA displayed
      characteristic signaling protein architecture, it is thought that this protein is
      a component of the signaling pathway controlling chemotaxis in Azospirillum.

PMID- 19390840
TI  - Mechanisms of telomere maintenance and attrition: linking cancer and ageing.

PMID- 19390841
TI  - Comparison of cardioprotective effects using salvianolic acid B and benazepril
      for the treatment of chronic myocardial infarction in rats. Naunyn-Schmiedeberg's
      Arch Pharmacol (2008) 378:311-322.

PMID- 19390842
TI  - Changes in the relative reinforcing effects of cigarette smoking as a function of
      initial abstinence.
AB  - RATIONALE: Experimental research is needed in investigating how early smoking
      abstinence affects relapse risk. OBJECTIVE: The present study assessed the
      feasibility of promoting smoking abstinence using once- rather than thrice-daily
      abstinence monitoring and the relationship between different durations of initial
      abstinence and changes in smoking preference. METHODS: Participants were 34 adult
      smokers randomized into one of two conditions: 14-day (14C) and 1-day (1C)
      contingent payment for smoking abstinence. Smoking status and participant ratings
      were assessed daily; a delay discounting task involving hypothetical money and an
      inter-temporal choice task involving hypothetical money and cigarettes were
      administered at baseline and days 7 and 14; a direct test of preference for
      smoking versus money was assessed on day 14. RESULTS: Once-daily monitoring
      gained robust experimental control over smoking abstinence. No differences in
      delay discounting for hypothetical money were observed between the two
      conditions. Compared to the 1C condition, participants in the 14C condition (1)
      showed significant increases in the mean percent of delayed hypothetical money
      over cigarettes choices in the inter-temporal choice task, (2) were significantly
      less likely to ever choose the smoking option in the direct test of preference
      for smoking versus money, and (3) reported greater ease of abstaining from
      smoking and lower nicotine withdrawal and craving. CONCLUSIONS: These results
      offer a more efficient procedure for experimentally promoting smoking abstinence,
      while providing further evidence that an initial period of sustained abstinence
      produces a profile of changes consistent with an overall lowering of relapse
      risk.

PMID- 19390844
TI  - Science outreach: an important endeavor for active scientists.

PMID- 19390843
TI  - Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two
      animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in
      attentional set-shifting.
AB  - RATIONALE: Therapies treating cognitive impairments in schizophrenia especially
      deficits in executive functioning are not available at present. OBJECTIVE: The
      current study evaluated the effect of ampakine CX516 in reversing deficits in
      executive functioning as represented in two animal models of schizophrenia and
      assessed by a rodent analog of the intradimensional-extradimensional (ID-ED)
      attentional set-shifting task. The second generation antipsychotic, sertindole,
      provided further validation of the schizophrenia-like disease models. METHODS:
      Animals were subjected to (a) sub-chronic or (b) early postnatal phencyclidine
      (PCP) treatment regimes: (a) Administration of either saline or PCP (5 mg/kg,
      intraperitonally b.i.d. for 7 days) followed by a 7-day washout period and
      testing on day 8. (b) On postnatal days (PNDs) 7, 9, and 11, rats were subjected
      to administration of either saline or PCP (20 mg/kg, subcutaneously (s.c.)) and
      tested on PNDs 56-95, after reaching adulthood. The single test session required
      rats to dig for food rewards in a series of discriminations following acute
      administration of either vehicle, or CX516 (5-40 mg/kg, s.c.), or sertindole
      (1.25 mg/kg, perorally). RESULTS: The specific extradimensional deficits produced
      by sub-chronic or early postnatal PCP treatment were significantly attenuated by
      sertindole and dose-dependently by CX516. CONCLUSION: Findings here further
      establish PCP treatment as model of executive functioning deficits related to
      schizophrenia and provide evidence that direct glutamatergic interventions could
      improve these, when assessed in the ID-ED attentional set-shifting task.

PMID- 19390845
TI  - New electrochemiluminescent biosensors combining polyluminol and an enzymatic
      matrix.
AB  - Performant reagentless electrochemiluminescent (ECL) (bio)sensors have been
      developed using polymeric luminol as the luminophore. The polyluminol film is
      obtained by cyclic voltammetry (CV) on a screen-printed electrode either in a
      commonly used H(2)SO(4) medium or under more original near-neutral buffered
      conditions. ECL responses obtained after performing polymerization either at
      acidic pH or at pH 6 have been compared. It appears that polyluminol formed in
      near-neutral medium gives the best responses for hydrogen peroxide detection.
      Polymerization at pH 6 by cyclic voltammetry gives a linear range extending from
      8 x 10(-8) to 1.3 x 10(-4) M H(2)O(2) concentrations. Based on this performant
      sensor for hydrogen peroxide detection, an enzymatic biosensor has been developed
      by associating the polyluminol film with an H(2)O(2)-producing oxidase. Here,
      choline oxidase (ChOD) has been chosen as a model enzyme. To develop the
      biosensor, luminol has been polymerized at pH 6 by CV, and then an enzyme
      entrapping matrix has been formed on the above modified working electrode.
      Different biological (chitosan, agarose, and alginate) and chemical (silica gels,
      photopolymers, or reticulated matrices) gels have been tested. Best performances
      have been obtained by associating a ChOD-immobilizing photopolymer with the
      polyluminol film. In this case, choline can be detected with a linear range
      extending from 8 x 10(-8) to 1.3 x 10(-4) M.

PMID- 19390846
TI  - Analysis of glutathione adducts of patulin by means of liquid chromatography
      (HPLC) with biochemical detection (BCD) and electrospray ionization tandem mass
      spectrometry (ESI-MS/MS).
AB  - A novel method for the identification of glutathione/electrophile adducts that
      are inhibiting glutathione-S-transferase (GST) activity was developed and applied
      for the analysis of the mycotoxin patulin. The method is based on high
      performance liquid chromatography (HPLC) coupled to a continuous-flow enzyme
      reactor serving as biochemical detector (BCD) in parallel to electrospray mass
      spectrometric detection (ESI-MS). This HPLC-BCD technique combines a separation
      step and the detection of the inhibition and is therefore ideally suited for the
      analysis of the activity of single patulin/glutathione adducts within a complex
      mixture of adducts. Two out of at least 15 detected patulin-glutathione adducts
      showed strong GST inhibition. In ESI-MS, the inhibitory active adducts were
      characterized by [M + H]+ ions with m/z 462.1138 and m/z 741.2011, respectively.
      They could be identified as a dihydropyranone adduct containing one molecule
      glutathione and a ketohexanoic acid bearing two glutathione molecules.

PMID- 19390847
TI  - Pial vasodilation and moderate hyperaemia following carotid endarterectomy: new
      MRI diagnostic signs in hyperperfusion/reperfusion syndrome?

PMID- 19390848
TI  - Diffusion tensor imaging and tractography of Rasmussen encephalitis.
AB  - A 5-year-old girl presented with intractable seizures and nonfocal hemispheric
      slowing on EEG. Blood, urine, and CSF laboratory values were all normal. MR
      imaging of the brain demonstrated diffuse volume loss of the entire left
      hemisphere. Clinical and imaging findings were consistent with the diagnosis of
      Rasmussen encephalitis. Diffusion tensor imaging demonstrated increased ADC
      values and decreased fractional anisotropy (FA) of the affected (left)
      hemisphere. Tractography data showed decreased numbers of lines drawn in the
      affected hemisphere, with fewer lines drawn at higher FA thresholds, relative to
      the contralateral hemisphere, or to normal age-matched controls. Diffusion tensor
      imaging offers an adjunct MR imaging modality in diagnosis and monitoring of this
      rare condition.

PMID- 19390849
TI  - Antenatal MR imaging of pulmonary lymphangiectasia secondary to hypoplastic left
      heart syndrome.
AB  - We report a case of pulmonary lymphangiectasia detected antenatally with MRI in a
      fetus with hypoplastic left heart syndrome and a restrictive atrial septum.

PMID- 19390850
TI  - Salt bridges in the miniature viral channel Kcv are important for function.
AB  - The viral potassium channel Kcv comprises only 94 amino acids, which represent
      the pore module of more complex K(+) channels. As for Kir-type channels, Kcv also
      has a short N-terminal helix exposed to the cytoplasm, upstream of the first
      transmembrane domain. Here we show that this helix is relevant for Kcv function.
      The presence of charged amino acids, which form dynamic inter- and intra-subunit
      salt bridges is crucial. Electrophysiological measurements, yeast rescue
      experiments and molecular dynamics simulations show that mutants in which the
      critical salt bridge formation is impaired have no or reduced channel activity.
      We conclude that these salt bridges destabilise the complexation of K(+) ions by
      negative charges on the inner transmembrane domain at the entrance into the
      cavity. This feature facilitates a continuous and coordinated transfer of ions
      between the cavity and the cytoplasm for channels without the canonical bundle
      crossing.

PMID- 19390851
TI  - Temperature influence on fluorescence intensity and enzyme activity of the fusion
      protein of GFP and hyperthermophilic xylanase.
AB  - By constructing the expression system for fusion protein of GFPmut1 (a green
      fluorescent protein mutant) with the hyperthermophilic xylanase obtained from
      Dictyoglomus thermophilum Rt46B.1, the effects of temperature on the fluorescence
      of GFP and its relationship with the activities of GFP-fused xylanase have been
      studied. The fluorescence intensities of both GFP and GFP-xylanase have proved to
      be thermally sensitive, with the thermal sensitivity of the fluorescence
      intensity of GFP-xylanase being 15% higher than that of GFP. The lost
      fluorescence intensity of GFP inactivated at high temperature of below 60 degrees
      C in either single or fusion form can be completely recovered by treatment at 0
      degrees C. By the fluorescence recovery of GFP domain at low temperature, the
      ratios of fluorescence intensity to xylanase activity (Rgfp/Axyl) at 15 degrees C
      and 37 degrees C have been compared. Even though the numbers of molecules of GFP
      and xylanase are equivalent, the Rgfp/Axyl ratio at 15 degrees C is ten times of
      that at 37 degrees C. This is mainly due to the fact that lower temperature is
      more conducive to the correct folding of GFP than the hyperthermophilic xylanase
      during the expression. This study has indicated that the ratio of GFP
      fluorescence to the thermophilic enzyme activity for the fusion proteins
      expressed at different temperatures could be helpful in understanding the folding
      properties of the two fusion partners and in design of the fusion proteins.

PMID- 19390852
TI  - Glucose exerts a negative effect over a peroxidase from Trichosporon asahii, with
      carotenoid cleaving activity.
AB  - Tobacco aroma compounds were generated via lutein cleavage by the combined action
      of a yeast and a bacterium identified as Trichosporon asahii and Paenibacillus
      amylolyticus, respectively. In this study, an inverse relationship between
      glucose concentration and the generation of three compounds, present in the
      tobacco aroma profile, was observed in mixed cultures. In order to identify the
      organism sensitive to the sugar effect, both were grown separately. The presence
      of glucose suppressed beta-ionone production by T. asahii grown with lutein.
      However, the biotransformation of the ionone into its reduced derivatives (7,8
      dihydro-beta-ionone and 7,8-dihydro-beta-ionol) by P. amylolyticus was not
      affected by the sugar. This pointed to the cleavage of lutein, a step within the
      process necessary for the synthesis of beta-ionone, as the target of the glucose
      effect. In vitro studies with crude extracts and concentrated cell-free medium
      derived from T. asahii cultures showed that the carotenoid breakdown activity was
      located extracellularly and only detected in supernatants from yeast cells grown
      in the absence of the sugar. Rather than an inhibition or a mechanism affecting
      the enzyme secretion, the glucose effect on lutein degradation comprised another
      regulatory level. Further experiments showed that the enzyme responsible for
      lutein breakdown and susceptible to the sugar effect exhibited a high degree of
      identity to fungal peroxidases, studied as well, for their involvement in
      carotenoid cleavage.

PMID- 19390853
TI  - Clinical features and molecular analysis in Thai patients with HbH disease.
AB  - We studied the alpha-globin gene abnormalities, the clinical features,
      hematologic values, growth assessment, transfusion therapy, and serum ferritin
      levels of patients with hemoglobin H (HbH) disease in southern Thailand. HbH
      disease in 83 of the 147 patients was the deletional type of HbH. The remaining
      64 patients was the nondeletional type of HbH disease. All 83 patients with the
      deletional type were double heterozygotes of alpha(0)-thalassemia and alpha(+)
      thalassemia. The Southeast Asian type of alpha(0)-thalassemia accounted for 98%
      of the Thai patients with HbH disease and the Thai type of alpha(0)-thalassemia
      made up the rest. A 3.7-kb deletion accounted for 91% of alpha(+)-thalassemia,
      and a 4.2-kb deletion made up the rest of the deletional type. In patients with
      nondeletional type of HbH disease, the Constant Spring variant was the majority
      of the disease. Newborns with a nondeletional genotype had higher mean
      corpuscular volume, had higher mean corpuscular hemoglobin, had higher red blood
      cell distribution width, had lower mean corpuscular hemoglobin concentration, and
      had higher proportions of Hb Bart's than those with a deletional genotype. Twenty
      one percent of children with HbH disease had growth deficiency. A genotype
      phenotype correlation was found; patients with the nondeletional type of HbH
      disease had more symptoms at a younger age, more severe hemolytic anemia, more
      growth deficiency, more dysmorphic facial features, larger spleens, larger
      livers, and higher serum ferritin levels and required more transfusions than
      patients with deletional HbH disease.

PMID- 19390854
TI  - Multiple scales and geometric structures: additional sources of randomness.

PMID- 19390856
TI  - Fibroadenomatoid mastopathy-like lesions arising in anogenital mammary-like
      glands in a 35-year-old man.

PMID- 19390855
TI  - Pupal developmental temperature and behavioral specialization of honeybee workers
      (Apis mellifera L.).
AB  - Honeybees (Apis mellifera) are able to regulate the brood nest temperatures
      within a narrow range between 32 and 36 degrees C. Yet this small variation in
      brood temperature is sufficient to cause significant differences in the behavior
      of adult bees. To study the consequences of variation in pupal developmental
      temperature we raised honeybee brood under controlled temperature conditions (32,
      34.5, 36 degrees C) and individually marked more than 4,400 bees, after
      emergence. We analyzed dancing, undertaking behavior, the age of first foraging
      flight, and forager task specialization of these workers. Animals raised under
      higher temperatures showed an increased probability to dance, foraged earlier in
      life, and were more often engaged in undertaking. Since the temperature profile
      in the brood nest may be an emergent property of the whole colony, we discuss how
      pupal developmental temperature can affect the overall organization of division
      of labor among the individuals in a self-organized process.

PMID- 19390857
TI  - Phlebosclerotic colitis with nonsurgical treatment.

PMID- 19390858
TI  - ErbB family immunohistochemical expression in colorectal cancer patients with
      higher risk of recurrence after radical surgery.
AB  - PURPOSE: Investigate ErbB family expression in colorectal cancer patients with
      higher risk of recurrence after surgical treatment. METHODS: We studied 109
      individuals with high risk stage II and stage III patients submitted to radical
      surgery. ErbB expression was assessed by tissue microarray technique. RESULTS:
      The immunohistochemical expression was considered positive for EGFR, ErbB2,
      ErbB3, ErbB4 membrane, and ErbB4 cytoplasmic in respectively 57.8%, 8.3%, 69.7%,
      11%, and 19.3% of patients. ErbB3 negative expression was associated with
      lymphovascular invasion. EGFR, ErbB2, and cytoplasmic ErbB4 expression was not
      associated with prognosis. Membranous positive ErbB4 expression was an
      independent prognostic factor for recurrence. ErbB3 negative expression was an
      independent prognostic factor for recurrence and survival in the multivariate
      analysis. CONCLUSIONS: The immunohistochemical expression of ErbB3 and ErbB4 may
      identify a subgroup with stage II and III colorectal cancer at higher risk of
      recurrence.

PMID- 19390859
TI  - Synaptic degeneration in Alzheimer's disease.
AB  - Synaptic loss is the major neurobiological substrate of cognitive dysfunction in
      Alzheimer's disease (AD). Synaptic failure is an early event in the pathogenesis
      that is clearly detectable already in patients with mild cognitive impairment
      (MCI), a prodromal state of AD. It progresses during the course of AD and in most
      early stages involves mechanisms of compensation before reaching a stage of
      decompensated function. This dynamic process from an initially reversible
      functionally responsive stage of down-regulation of synaptic function to stages
      irreversibly associated with degeneration might be related to a disturbance of
      structural brain self-organization and involves morpho-regulatory molecules such
      as the amyloid precursor protein. Further, recent evidence suggests a role for
      diffusible oligomers of amyloid beta in synaptic dysfunction. To form synaptic
      connections and to continuously re-shape them in a process of ongoing structural
      adaptation, neurons must permanently withdraw from the cell cycle. Previously, we
      formulated the hypothesis that differentiated neurons after having withdrawn from
      the cell cycle are able to use molecular mechanisms primarily developed to
      control proliferation alternatively to control synaptic plasticity. The existence
      of these alternative effector pathways within neurons might put them at risk of
      erroneously converting signals derived from plastic synaptic changes into the
      program of cell cycle activation, which subsequently leads to cell death. The
      molecular mechanisms involved in cell cycle activation might, thus, link aberrant
      synaptic changes to cell death.

PMID- 19390860
TI  - Schistosoma mansoni: an unusual cause of ovarian pseudotumor.
AB  - BACKGROUND: Schistosomiasis is a disease prevalent throughout the world, but the
      involvement of ovary by Schistosoma mansoni eggs is rarely found. The
      pathological mechanisms involved in the infestation of the ovary remain unknown
      and the diagnosis usually occurs, retrospectively, by histopathological
      examination. An uncommon case of ovarian pseudotumor due to Manson's
      schistosomiasis is reported. CASE: A 40-year-old woman referred with recurrent
      poorly characterized pelvic pain underwent surgical exploration and right
      salpingo-oophorectomy to treat a mixed cystic and solid ovarian tumor
      demonstrated preoperatively by transvaginal ultrasound of pelvis. The
      pathological examination of surgical product revealed a pseudotumor due to
      granulomatous reaction triggered by eggs of S. mansoni. The patient was referred
      to clinical treatment with oxamniquine and remained asymptomatic for a year
      follow-up. CONCLUSIONS: Ovarian ectopic S. mansoni is rarely reported in the most
      current literature; however, this actual proportion of ovarian Manson's
      schistosomiasis may not represent the real female genital involvement rates and
      reflect an underestimation of internal genital disease.

PMID- 19390861
TI  - Lens capsular bag irrigation for low-grade endophthalmitis.
AB  - PURPOSE: In postoperative low-grade endophthalmitis, microorganisms of low
      pathogenicity exhibit prolonged survival times by sequestration into the capsular
      bag. Thus, removal or irrigation of the capsular bag as nidus of the
      microorganisms is an essential therapeutic step. Correspondingly, guidelines
      suggest pars plana vitrectomy, capsulectomy and/or intraocular lens removal.
      Here, we report on capsular bag irrigation alone as an alternative, minimally
      invasive therapeutic method for postoperative infectious low-grade
      endophthalmitis. METHODS: Nine patients consecutively presenting with whitish
      precipitates in the capsular bag, anterior chamber inflammation and mild vitritis
      2 weeks to 6 months following uncomplicated cataract surgery were included. Using
      an irrigation/aspiration cannula, synechiae were opened, the intraocular lens was
      rotated within the intact capsular bag and irrigated with 30 ml Ringer's solution
      containing 0.16 mg/ml gentamicin and 0.04 mg/ml vancomycin in topical
      anaesthesia. RESULTS: In all patients, the inflammation subsided within 2 days to
      2 weeks. Visual acuity improved in all patients, mostly to post cataract surgery
      levels. Visual acuity remained stable during follow-up ranging from 2 to 39
      months. No further interventions were required. CONCLUSIONS: The results suggest
      that capsular bag irrigation as first and single surgical step can be a useful,
      minimally invasive procedure in the surgical armamentarium for the treatment of
      infectious low-grade endophthalmitis. It may avoid removal of the intraocular
      lens and reduce the surgical risks of more complex procedures.

PMID- 19390862
TI  - Campylobacter jejuni infection associated with myopericarditis in adolescents:
      report of two cases.
AB  - Two cases of myopericarditis associated with Campylobacter jejuni infection in
      male adolescents are presented. C. jejuni is the most common cause of bacterial
      gastroenteritis worldwide; however, cardiac complications are rare, even in
      adults. To our knowledge, these are the first reported cases of campylobacter
      related myopericarditis in adolescents.

PMID- 19390863
TI  - Bayesian latent trait modeling of migraine symptom data.
AB  - Definition of disease phenotype is a necessary preliminary to research into
      genetic causes of a complex disease. Clinical diagnosis of migraine is currently
      based on diagnostic criteria developed by the International Headache Society.
      Previously, we examined the natural clustering of these diagnostic symptoms using
      latent class analysis (LCA) and found that a four-class model was preferred.
      However, the classes can be ordered such that all symptoms progressively
      intensify, suggesting that a single continuous variable representing disease
      severity may provide a better model. Here, we compare two models: item response
      theory and LCA, each constructed within a Bayesian context. A deviance
      information criterion is used to assess model fit. We phenotyped our population
      sample using these models, estimated heritability and conducted genome-wide
      linkage analysis using Merlin-qtl. LCA with four classes was again preferred.
      After transformation, phenotypic trait values derived from both models are highly
      correlated (correlation = 0.99) and consequently results from subsequent genetic
      analyses were similar. Heritability was estimated at 0.37, while multipoint
      linkage analysis produced genome-wide significant linkage to chromosome 7q31-q33
      and suggestive linkage to chromosomes 1 and 2. We argue that such continuous
      measures are a powerful tool for identifying genes contributing to migraine
      susceptibility.

PMID- 19390864
TI  - Population programs for the detection of couples at risk for severe monogenic
      genetic diseases.
AB  - Population genetic screening programs for carrier detection of severe genetic
      disorders exist worldwide, mainly for beta-thalassemia. These screening programs
      are either mandatory or voluntary. In several Arab countries and Iran, the state
      has made thalassemia carrier detection mandatory, while tests for detecting
      carriers are required by the religious authorities in Cyprus. In all the existing
      mandatory genetic screening programs, the couples have to get the information
      about the tests before marriage, but the decision whether or not to marry is left
      to them. Voluntary programs exist for instance in several Mediterranean countries
      for the prevention of thalassemia and for several genetic diseases among Jews.
      While voluntary programs leave the decision to be screened or not to the
      individual, a major problem is that in many cases awareness about the existence
      of screening tests is very sparse. Some programs, for instance in Canada or
      Australia, therefore provide education about genetic tests and screening at
      school in order to allow the individuals to be able to make an informed decision
      about their reproductive choices.

PMID- 19390865
TI  - Nuclear transport of protein TTC4 depends on the cell cycle.
AB  - TTC4 (tetratricopeptide repeat domain protein 4) is a putative tumor suppressor
      involved in the transformation of melanocytes. At present, the relationships
      between TTC4 and DNA replication proteins are largely unknown, as are the tissue
      distribution and subcellular localization of TTC4. Using reverse transcription
      with the polymerase chain reaction, we have observed that the murine TTC4 gene is
      ubiquitously expressed. Analysis of the TTC4 subcellular localization has shown
      that, upon overexpression, TTC4 localizes to the cytoplasm. Interestingly, co
      expression with a known protein interaction partner, hampin/MSL1, results in the
      nuclear translocation of the TTC4 protein. The subcellular localization of
      endogenous TTC4 depends, however, on the cell cycle: it is mostly nuclear in the
      G1 and S phases and is evenly distributed between the nucleus and cytoplasm in
      G2. The nuclear transport of TTC4 is apparently a complex process dependent on
      interactions with other proteins during the progression of the cell cycle. Thus,
      the dynamic character of the nuclear accumulation of TTC4 might be a potential
      link with regard to its function in tumor suppression.

PMID- 19390866
TI  - A network analysis of plant-pollinator interactions in temperate rain forests of
      Chiloe Island, Chile.
AB  - This study characterizes the structure of a plant-pollinator network in a
      temperate rain forest of Chiloe Island, southern Chile, where woody species are
      strongly dependent on biotic pollinators, and analyzes its robustness to the loss
      of participating species. Degree distribution, nestedness, and expected species
      persistence were evaluated. In addition, we assessed the roles of predefined
      subsets of plants (classified by life forms) and pollinators (grouped by
      taxonomic orders) in the network's structure and dynamics. For this, we simulated
      the complete removal of each plant and pollinator subset and analyzed the
      resultant connectivity patterns, as well as the expected long-term species losses
      by running a stochastic model. Finally, we evaluated the sensitivity of the
      network structure to the loss of single species in order to identify potential
      targets for conservation. Our results show that the plant-pollinator network of
      this Chilean temperate rain forest exhibits a nested structure of interactions,
      with a degree distribution best described by a power law model. Model simulations
      revealed the importance of trees and hymenopterans as pivotal groups that
      maintain the core structure of the pollination network and guarantee overall
      species persistence. The hymenopterans Bombus dahlbomii and Diphaglossa gayi, the
      shrubs Tepualia stipularis and Ugni molinae, the vines Mitraria coccinea and
      Asteranthera ovata, and the entire set of tree species exerted a
      disproportionately large influence on the preservation of network structure and
      should be considered as focal species for conservation programs given current
      threats from selective logging and habitat loss.

PMID- 19390867
TI  - The effects of primiparity on reproductive performance in the brown bear.
AB  - We studied the effects of primiparity on litter size, offspring size, and cub
      loss in brown bears (Ursus arctos) in two study areas (north, south) in Sweden
      from 1987 to 2006. Sexually selected infanticide (SSI) has been suggested
      previously as a mortality factor in our study populations. Females in the south
      became primiparous earlier than females in the north. Primiparous females had
      significantly smaller litters of cubs than multiparous females. We found no
      evidence that primiparity was costly in terms of the interlitter interval.
      Primiparous mothers had a higher probability of cub loss than multiparous
      mothers. The probability of cub loss was analyzed separately for the pre-mating
      and the mating season. The probability of cub loss by primiparous females in the
      pre-mating season increased with both increasing population density and
      deteriorating food conditions, whereas the probability of cub loss during the
      mating season decreased with increasing age of primiparity and increased with
      male turnover (a variable predicting SSI). The temporal patterns of cub loss by
      primiparous females suggested that the critical times for reproductive success by
      primiparous females were the pre-mating season (from birth to shortly after
      leaving the den) and the mating season. Cub loss in these periods was independent
      and caused by different factors. Cub loss before the mating season seemed to be
      most influenced by food conditions, whereas that during the mating season
      appeared to be caused by SSI.

PMID- 19390868
TI  - Behavioral archives link the chemistry and clonal structure of trembling aspen to
      the food choice of North American porcupine.
AB  - Understanding the links among plant genotype, plant chemistry, and food selection
      by vertebrate herbivores is critical to assess the role of herbivores in the
      evolution of plant secondary chemistry. Some specialized vertebrate herbivores
      have been shown to select plants differentially according to plant genotype, but
      examples from generalists, which constitute the vast majority of vertebrate
      herbivores, are few, especially in natural conditions. We examined the
      relationship between the North American porcupine (Erethizon dorsatum), a
      generalist mammalian herbivore, and clonal trembling aspen (Populus tremuloides),
      a preferred food source of porcupines. We determined preference for certain aspen
      trees through visual examination of porcupine climbing scars left on tree bark,
      and through a controlled feeding experiment. We used genetic and biochemical
      analyses to link the behavioral archives (climbing scars) left by porcupines on
      aspen trunks to the clonal structure and chemical composition of trees. We show
      that two phenolic glycosides (tremulacin and salicortin), which are under a high
      degree of genetic control and thus vary in concentration across clones, are the
      chemical variables that most influence (deter) feeding choices by porcupines.
      Using behavioral archives left by a wild herbivore on a natural stand of plants
      thus allowed us to demonstrate that a generalist vertebrate herbivore can choose
      plants according to their clonal structure and genetically based chemical
      composition. Our results contribute to extending previous findings obtained with
      generalist herbivores studied in controlled conditions, and with specialist
      herbivores studied in the field.

PMID- 19390869
TI  - Placing biodiversity and ecosystem functioning in context: environmental
      perturbations and the effects of species richness in a stream field experiment.
AB  - Greater biodiversity is often associated with increased ecosystem process rates,
      and is expected to enhance the stability of ecosystem functioning under abiotic
      stress. However, these relationships might themselves be altered by environmental
      factors, complicating prediction of the effects of species loss in ecosystems
      subjected to abiotic stress. In boreal streams, we investigated effects of
      biodiversity and two abiotic perturbations on three related indices of ecosystem
      functioning: leaf decomposition, detritivore leaf processing efficiency (LPE) and
      detritivore growth. Replicate field enclosures containing leaves and detritivore
      assemblages were exposed to liming and nutrient enrichment, raising pH and
      nutrient levels. Both treatments constitute perturbations for our naturally
      acidic and nutrient-poor streams. We also varied detritivore species richness and
      density. The effects of the abiotic and diversity manipulations were similar in
      magnitude, but whereas leaf decomposition increased by 18% and 8% following
      liming and nutrient enrichment, respectively, increased detritivore richness
      reduced leaf decomposition (6%), detritivore LPE (19%) and detritivore growth
      (12%). The detritivore richness effect on growth was associated with negative
      trait-independent complementarity, indicating interspecific interference
      competition. These interactions were apparently alleviated in both enriched and
      limed enclosures, as trait-independent complementarity became less negative. LPE
      increased with detritivore density in the monocultures, indicating benefits of
      intra-specific aggregation that outweighed the costs of intra-specific
      competition, and dilution of these benefits probably contributed to lowered leaf
      decomposition in the species mixtures. Finally, the effects of liming were
      reduced in most species mixtures relative to the monocultures. These results
      demonstrate how environmental changes might regulate the consequences of species
      loss for functioning in anthropogenically perturbed ecosystems, and highlight
      potential influences of biodiversity on functional stability. Additionally, the
      negative effects of richness and positive effects of density in our field study
      were opposite to previous laboratory observations, further illustrating the
      importance of environmental context for biodiversity-ecosystem functioning
      relationships.

PMID- 19390870
TI  - Psychosocial adjustment of family caregivers of head and neck cancer survivors.
AB  - PURPOSE: This study examined the psychosocial adjustment and needs of family
      caregivers of head and neck cancer survivors at 6-24 months posttreatment.
      MATERIALS AND METHODS: Family caregivers of head and neck cancer survivors (N=89)
      completed mailed questionnaires that assessed demographic variables, mental
      health, quality of life, and practical and informational needs. RESULTS: Thirty
      eight percent of caregivers reported moderate to high distress. However, quality
      of life scores for the entire sample (N=89) were better than the scores reported
      in initial validation studies on caregivers of patients undergoing active cancer
      treatment. Greater time spent caregiving was associated with worse psychological
      well-being, but also more positive adaptation to caregiving. In addition, 39% of
      caregivers reported that all of their practical and informational needs were
      being met. CONCLUSIONS: Findings suggest that research and clinical efforts are
      needed to address the psychosocial concerns of this population.

PMID- 19390871
TI  - Effectiveness of posterior tension band fixation in the thoracolumbar seat-belt
      type injuries of the young population.
AB  - We report results in the surgical treatment of thoracolumbar flexion-distraction
      fractures, both associated or not with neurological impairment. Items in the
      present study include function, pain (back pain rating scale) and neurological
      recovery (Asia Score). A prospective series of 19 consecutive flexion-extension
      thoracolumbar injuries (T11-L2), occurred in young patients (20-33 years) due to
      motor vehicle crashes wearing the 3-point safety belts, includes 2 Chance and 17
      seat-belt fractures, with different amount of vertebral dislocation and
      neurological impairment. Fractures have been evaluated according to the Magerl's
      classification. All patients were operated via posterior approach using hybrid
      instrumentation or short pedicular fixation to reduce dislocation and to obtain
      spinal fusion. Posterior decompression was performed in all patients with
      neurological deficit. Posterior instrumented arthodesis was performed by wide
      constructs that preferably include 2 levels above and below the dislocated
      vertebra. Most of them were instrumented using thoracic hooks and lumbar
      pedicular screws. One postoperative vascular complication was successfully
      treated by selective embolization. All neurological patients were submitted to a
      postoperative rehabilitation program. Posterior procedure allows proper reduction
      and realignment. In our experience, the use of laminar hooks one level above the
      dislocation seems to reduce the potential risk of neurological and /or vascular
      damage during the intraoperative maneuvers on the dislocated pedicles. At follow
      up, fusion was achieved in all patients. The clinical condition was totally
      satisfactory due to the absence of significant pain, confirming mechanical
      stability of the implants. In terms of neurological outcomes, patients presenting
      as ASIA A-B or ASIA E, maintained their preoperative neurological condition.
      Surgical treatment, together with an early postoperative rehabilitation program,
      can be of paramount importance in neurological patients' quality of life.

PMID- 19390874
TI  - The patient's perspective on complications after spine surgery.
AB  - Recent years have witnessed a paradigm shift in relation to the assessment of
      outcome in spine surgery: multidimensional patient-centred questionnaires have
      superseded traditional surgeon-based ratings of outcome, and surgical registries
      have been developed to capitalise on the principle of "strength in numbers."
      However, the assessment of complications has not enjoyed this same enlightened
      patient-centred approach. The present study investigated post-surgical
      complications from the patient's perspective. All German-speaking patients
      undergoing surgery within our Spine Center in 2005 were asked to complete the
      patient-orientated Core Measures Outcome Index of the SSE Spine Tango Spine
      Surgery Registry before and 12 months after surgery; the surgeon completed a
      Spine Tango surgery form. In the 12-month questionnaire, the patient was asked,
      "did any complications arise as a consequence of your operation 1 year ago (e.g.
      problems with wound healing, paralysis, sensory disturbances, etc.)? If so, give
      details." Patients were also asked about their satisfaction with the operation
      and the global outcome of surgery. 1,035 patients were sent a 12-month
      questionnaire; 972 (94%) returned the completed questionnaire. 29% patients
      answered "yes" to the question about complications. The incidence of patient
      rated complications was significantly associated with outcome/satisfaction (P <
      0.05), suggesting these complications were not trivial to the patient. The
      results indicate that, just like outcome, "complications" should be assessed from
      both the patient's and the surgeon's perspectives, not least to better understand
      the reasons accounting for dissatisfaction and a poor patient-rated outcome.

PMID- 19390872
TI  - Lumbosacral lordosis in fetal spine: genetic or mechanic parameter.
AB  - Many believe that the fetus spine had only one curvature from cranial to caudal
      which is a global kyphosis and that the lumbosacral lordosis appears with the
      erect posture. They agree that the sacrum of Homo sapiens is not positioned
      posteriorly at birth and that it is during the first few years that the sacrum,
      in humans, moves dorsally in relation with the progressive acquisition of erect
      posture and the ontogeny of bipedal locomotion. Nevertheless, there is no
      biometric study assessing these parameters in vivo in utero during the fetal
      life. Cross-sectional biometric study of the lumbosacral junction of the spine in
      in utero fetuses was to document the presence of a lumbosacral lordosis in the
      fetal population in utero long before standing and walking and its change during
      growth. Forty-five MRIs (magnetic resonance imaging) of fetuses aged of 23-40
      weeks of gestation were analyzed. The measurements were performed on computerized
      MRI DICOM images using a professional software to calculate the curvature and
      radius of the lumbosacral junction. The presence or absence of visual lumbosacral
      lordosis was noted for each case. Correlation tests were performed in order to
      disclose a correlation between the gestational age and the curvature calculated.
      A test was considered significant for P < 0.01. There were 14 males, 17 females
      and 14 undetermined. All the curves (100%) showed mathematically the presence of
      a lordosis in the lumbosacral region. The visual lumbosacral lordosis was present
      in 60% of cases. The measurement of the lumbosacral curvature varies between 
      0.133 and -0.033 mm(-1) and a mean of -0.054 mm(-1) with a corresponding radius
      ranging from -7 to -303 mm with a mean of -18.7 mm. The statistical analysis
      showed no correlation between the gestational age and the lumbosacral curvature
      (R (2) = 0.11). The hypothesis of increased lumbosacral lordosis with gestational
      age is rejected. It is difficult to accurately determine the role played
      separately by genetics and by erect posture. A visual lumbosacral lordosis was
      noted in 60% of cases with mean radius of -18.6691 mm. This lordosis was not
      correlated statistically to gestational age which means that it is not related to
      growth and might be genetically determined. Mechanical factors may play a major
      role in the determination of the shape of the growing pelvis. One can ask if the
      pelvis morphology is genetically determined or if it is mechanically determined
      under muscular and ligamentous stresses. This study shows that the sacrum of
      human fetuses is oriented posteriorly mathematically in 100% of cases, and in 60%
      of cases based on the morphologic appearance of the lumbosacral junction. So
      beside the effect of progressive acquisition of erect posture and bipedalism in
      determining the formation of lumbosacral angle, we believe that genetics play an
      important role in the formation of the lumbosacral angle.

PMID- 19390875
TI  - Pneumocranium secondary to halo vest pin penetration through an enlarged frontal
      sinus.
AB  - We present a case report of a patient with pneumocranium secondary to halo vest
      pin penetration and a review of literature. The objectives of this study are to
      report a rare complication of halo vest pin insertion and to discuss methods of
      prevention of this complication. Halo vest orthosis is a commonly used and well
      tolerated upper cervical spinal stabilizing device. Reports of complications
      related to pin penetration is rare and from our review, there has been no reports
      of pneumocranium occurring from insertion of pins following standard anatomical
      landmarks. A 57-year-old male sustained a type 1 traumatic spondylolisthesis of
      C2/C3 following a motor vehicle accident. During application of the halo vest,
      penetration of the left anterior pin through the abnormally enlarged frontal
      sinus occurred. The patient developed headache, vomiting and CSF rhinorrhoea over
      his left nostril. He was treated with intravenous Ceftriaxone for 1 week. This
      resulted in resolution of his symptoms as well as the pneumocranium. In
      conclusion, complications of halo vest pin penetration are rare and need
      immediate recognition. Despite the use of anatomical landmarks, pin penetration
      is still possible due to aberrant anatomy. All patients should have a skull X-ray
      with a radio-opaque marker done prior to placement of the halo vest pins and halo
      vest pins have to be inserted by experienced personnel to enable early detection
      of pin penetration.

PMID- 19390876
TI  - Posterior pelvic pain provocation test is negative in patients with lumbar
      herniated discs.
AB  - The classification of pelvic girdle pain can only be reached after lumbar causes
      have been excluded by a clinical examination. During clinical examination, the
      posterior pelvic pain provocation test is a well-established method for verifying
      pelvic girdle pain. However, a criticism of pelvic pain provocation tests is that
      they may have an effect on lumbar structures, thus yielding false-positive
      results. The posterior pelvic pain provocation test was performed with four
      groups of patients: patients with computed tomography-verified disc herniations
      (1) on the waiting list for surgery (14 women; 9 men); (2) 6 weeks after disc
      surgery (18 women, 12 men); (3) pregnant women seeking care for pelvic girdle
      pain (n = 25); and (4) women with persistent pelvic girdle pain after delivery (n
      = 32). The sensitivity of the posterior pelvic pain provocation test was 0.88 and
      the specificity was 0.89. The positive predictive value was 0.89 and the negative
      predictive value was 0.87. Analysis of only women showed similar results. In our
      study, the posterior pelvic pain provocation test was negative in patients with a
      well-defined lumbar diagnosis of lumbar disc herniation, both before and after
      disc surgery. Our results are an important step toward the more accurate
      classification of lumbopelvic pain.

PMID- 19390877
TI  - Gait in adolescent idiopathic scoliosis: energy cost analysis.
AB  - Walking is a very common activity for the human body. It is so common that the
      musculoskeletal and cardiovascular systems are optimized to have the minimum
      energetic cost at 4 km/h (spontaneous speed). A previous study showed that lumbar
      and thoracolumbar adolescent idiopathic scoliosis (AIS) patients exhibit a
      reduction of shoulder, pelvic, and hip frontal mobility during gait. A longer
      contraction duration of the spinal and pelvic muscles was also noted. The
      energetic cost (C) of walking is normally linked to the actual mechanical work
      muscles have to perform. This total mechanical work (W(tot)) can be divided in
      two parts: the work needed to move the shoulders and lower limbs relative to the
      center of mass of the body (COM(b)) is known as the internal work (W(int)),
      whereas additional work, known as external work (W(ext)), is needed to accelerate
      and lift up the COM(b) relative to the ground. Normally, the COM(b) goes up and
      down by 3 cm with every step. Pathological walking usually leads to an increase
      in W (tot) (often because of increased vertical displacement of the COM(b)), and
      consequently, it increases the energetic cost. The goal of this study is to
      investigate the effects of scoliosis and scoliosis severity on the mechanical
      work and energetic cost of walking. Fifty-four female subjects aged 12 to 17 were
      used in this study. Thirteen healthy girls were in the control group, 12 were in
      scoliosis group 1 (Cobb angle [Cb] < or = 20 degrees), 13 were in scoliosis group
      2 (20 degrees < Cb < 40 degrees), and 16 were in scoliosis group 3 (Cb > or = 40
      degrees). They were assessed by physical examination and gait analysis. The 41
      scoliotic patients had an untreated progressive left thoracolumbar or lumbar AIS.
      During gait analysis, the subject was asked to walk on a treadmill at 4 km h(-1).
      Movements of the limbs were followed by six infrared cameras, which tracked
      markers fixed on the body. W(int) was calculated from the kinematics. The
      movements of the COM(b) were derived from the ground reaction forces, and W(ext)
      was calculated from the force signal. W(tot) was equal to W(int) + W(ext). Oxygen
      consumption VO2 was measured with a mask to calculate energetic cost (C) and
      muscular efficiency (W(tot)/C). Statistical comparisons between the groups were
      performed using an analysis of variance (ANOVA). The external work (W(ext)) and
      internal work (W(int)) were both reduced from 7 to 22% as a function of the
      severity of the scoliosis curve. Overall, the total muscular mechanical work
      (W(tot)) was reduced from 7% to 13% in the scoliosis patients. Within scoliosis
      groups, the W(ext) for the group 1 (Cb > or = 20 degrees) and 2 (20 < or = Cb <
      or = 40 degrees) was significantly different from group 3 (Cb > or = 40 degrees).
      No significant differences were observed between scoliosis groups for the W(int).
      The W(tot) did not showed any significant difference between scoliosis groups
      except between group 1 and 3. The energy cost and VO2 were increased by around
      30%. As a result Muscle efficiency was significantly decreased by 23% to 32%, but
      no significant differences related to the severity of the scoliosis were noted.
      This study shows that scoliosis patients have inefficient muscles during walking.
      Muscle efficiency was so severely decreased that it could be used as a diagnostic
      tool, since every scoliosis patient had an average muscle efficiency below 27%,
      whereas every control had an average muscle efficiency above 27%. The reduction
      of mechanical work found in scoliotic patients has never been observed in any
      pathological gait, but it is interpreted as a long term adaptation to economize
      energy and face poor muscle efficiency. With a relatively stiff gait, scoliosis
      patients also limit vertical movement of the COM(b) (smoothing the gait) and
      consequently, reduce W(ext) and W(int). Inefficiency of scoliosis muscles was
      obvious even in mild scoliosis (group 1, Cb < 20 degrees) and could be related to
      the prolonged muscle contraction time observed in a previous study (muscle co
      contraction).

PMID- 19390879
TI  - A proposed mechanism for the inhibitory effect of the anticancer agent titanocene
      dichloride on tumour gelatinases and other proteolytic enzymes.
AB  - Titanocene dichloride, the most studied metallocene, exhibits antiproliferative
      activity in a wide spectrum of murine and human tumours. In this article it is
      demonstrated that titanocene dichloride inhibits tumour gelatinases in a dose
      dependent manner. Substrate saturation experiments and the fact that the IC(50)
      values were increased in correlation with collagen substrate concentrations
      indicate that the titanocene dichloride induced inhibition is of a competitive
      type. Titanocene dichloride also specifically inhibits clostridium collagenase
      and trypsin, particularly when collagens are used as substrates. Binding
      experiments demonstrate that cyclopentadiene-Ti(IV) moieties, resulting from
      titanocene dichloride at physiological pH, are bound mainly to different types of
      collagens and to a lesser extent to casein or bovine serum albumin, forming
      soluble and stable adducts. These results indicate that titanocene dichloride
      behaves as a competitive inhibitor against various proteolytic enzymes by binding
      to the substrate rather than to the enzyme active site. This property may be
      responsible for the antiangiogenic effect of titanocene dichloride and
      additionally contributes to its anticancer action.

PMID- 19390880
TI  - Novel organometallic cationic ruthenium(II) pentamethylcyclopentadienyl
      benzenesulfonamide complexes targeted to inhibit carbonic anhydrase.
AB  - Cationic ruthenium(II) pentamethylcyclopentadienyl benzenesulfonamide sandwich
      complexes have been synthesized and screened for enzymatic inhibition of the
      physiologically dominant carbonic anhydrase (CA) isozymes: human CA I and II,
      mitochondrial isozymes VA and VB, and the cancer-associated isozyme IX. The
      complexes demonstrated weaker binding to CAs compared with typical aromatic
      sulfonamides, inhibiting the enzyme at high nanomolar concentrations. An in vitro
      cytotoxic evaluation of the complexes was also undertaken against a range of
      tumorigenic cell lines and a healthy human cell line. Complexes inhibited the
      growth of cancerous cells at low micromolar concentrations while expressing lower
      levels of toxicity towards the normal human cell line. Factors influencing the
      synthesis, cytotoxicity, and enzyme affinity for this series of organometallic
      complexes are discussed.

PMID- 19390878
TI  - DNA adducts of antitumor cisplatin preclude telomeric sequences from forming G
      quadruplexes.
AB  - We studied the effect of antitumor cisplatin and inefficient transplatin on the
      structure and stability of G quadruplexes formed by the model human telomere
      sequence 5'-GGG(TTAGGG)(3)-3' using circular dichroism, UV-monitored thermal
      denaturation, and gel electrophoresis. In addition, to investigate whether there
      is a connection between the ability of cisplatin or transplatin to affect
      telomerase activity and stability of G quadruplexes, we also used a modified
      telomere repeat amplification protocol assay that uses an oligonucleotide
      substrate for telomerase elongation susceptible to forming a G quadruplex. The
      results indicate that cisplatin is more efficient than transplatin in disturbing
      the quadruplex structure, thereby precluding telomeric sequences from forming
      quadruplexes. On the other hand, the results of this work also demonstrate that
      in absence of free platinum complex, DNA adducts of antitumor cisplatin inhibit
      telomerase catalysis, so the mechanism underlying this inhibition does not
      involve formation of the G quadruplexes which are not elongated by telomerase.

PMID- 19390881
TI  - Study of cellulases from a newly isolated thermophilic and cellulolytic
      Brevibacillus sp. strain JXL.
AB  - A potentially novel aerobic, thermophilic, and cellulolytic bacterium designated
      as Brevibacillus sp. strain JXL was isolated from swine waste. Strain JXL can
      utilize a broad range of carbohydrates including: cellulose,
      carboxymethylcellulose (CMC), xylan, cellobiose, glucose, and xylose. In two
      different media supplemented with crystalline cellulose and CMC at 57 degrees C
      under aeration, strain JXL produced a basal level of cellulases as FPU of 0.02
      IU/ml in the crude culture supernatant. When glucose or cellobiose was used
      besides cellulose, cellulase activities were enhanced ten times during the first
      24 h, but with no significant difference between these two simple sugars. After
      that time, however, culture with glucose demonstrated higher cellulase activities
      compared with that from cellobiose. Similar trend and effect on cellulase
      activities were also obtained when glucose or cellobiose served as a single
      substrate. The optimal doses of cellobiose and glucose for cellulase induction
      were 0.5 and 1%. These inducing effects were further confirmed by scanning
      electron microscopy (SEM) images, which indicated the presence of extracellular
      protuberant structures. These cellulosome-resembling structures were most
      abundant in culture with glucose, followed by cellobiose and without sugar
      addition. With respect to cellulase activity assay, crude cellulases had an
      optimal temperature of 50 degrees C and a broad optimal pH range of 6-8. These
      cellulases also had high thermotolerance as evidenced by retaining more than 50%
      activity at 100 degrees C after 1 h. In summary, this is the first study to show
      that the genus Brevibacillus may have strains that can degrade cellulose.

PMID- 19390882
TI  - Decolorization of Direct Red 28 by mixed bacterial culture in an up-flow
      immobilized bioreactor.
AB  - Aerobic mixed bacterial culture comprised of five isolates (Bacillus
      vallismortis, B. pumilus, B. cereus, B. subtilis and B. megaterium) identified by
      16srDNA analysis was developed from wastewater samples from the aeration tank of
      an effluent treatment plant of a textile and dyeing industry and evaluated for
      its ability to decolorize azo dye Direct Red 28 in an up-flow immobilized packed
      bed bioreactor using marble chips as support matrix. The bioreactor was operated
      under two parameters: an aeration rate of 0.4 and 0.6 mmol/min at a flow rate of
      60, 90 and 120 ml/h, respectively. At a constant aeration rate of 0.4 mmol/min
      and with flow rates of 60, 90 and 120 ml/h, optimum decolorization of 91, 75 and
      72% was observed, while at an aeration rate of 0.6 mmol/min and flow rates of 60,
      90 and 120 ml/h, optimum decolorization of 93, 78 and 72% was observed over 10
      days. The study concluded that across the two aeration rates and the respective
      flow rates, the higher aeration rate of 0.6 mmol/min along with a flow rate of 60
      ml/h was best suited to decolorize Direct Red 28 in the packed bed bioreactor.
      Spectral changes of the input and output of the bioreactor by UV-visible
      spectroscopy indicated decolorization of the dye solution by degradation in
      addition to the visual observation of the biosorption process.

PMID- 19390883
TI  - Enantioselective behavior of lipases from Aspergillus niger immobilized in
      different supports.
AB  - Considering the extraordinary microbial diversity and importance of fungi as
      enzyme producers, the search for new biocatalysts with special characteristics
      and possible applications in biocatalysis is of great interest. Here, we report
      the performance in the resolution of racemic ibuprofen of a native
      enantioselective lipase from Aspergillus niger, free and immobilized in five
      types of support (Accurel EP-100, Amberlite MB-1, Celite, Montmorillonite K10 and
      Silica gel). Amberlite MB-1 was found to be the best support, with a conversion
      of 38.2%, enantiomeric excess of 50.7% and enantiomeric ratio (E value) of 19 in
      72 h of reaction. After a thorough optimization of several parameters, the E
      value of the immobilized Aspergillus niger lipase was increased (E = 23) in a
      shorter reaction period (48 h) at 35 degrees C. Moreover, the immobilized
      Aspergillus niger lipase maintained an esterification activity of at least 80%
      after 8 months of storage at 4 degrees C and could be reused at least six times.

PMID- 19390884
TI  - Molecular and biochemical characterization of an extracellular serine-protease
      from Vibrio metschnikovii J1.
AB  - A protease-producing bacterium was isolated from an alkaline wastewater of the
      soap industry and identified as Vibrio metschnikovii J1 on the basis of the 16S
      rRNA gene sequencing and biochemical properties. The strain was found to over
      produce proteases when it was grown at 30 degrees C in media containing casein as
      carbon source (14,000 U ml(-1)). J1 enzyme, the major protease produced by V.
      metschnikovii J1, was purified by a three-step procedure, with a 2.1-fold
      increase in specific activity and 33.3% recovery. The molecular weight of the
      purified protease was estimated to be 30 kDa by SDS-PAGE and gel filtration. The
      N-terminal amino acid sequence of the first 20 amino acids of the purified J1
      protease was AQQTPYGIRMVQADQLSDVY. The enzyme was highly active over a wide range
      of pH from 9.0 to 12.0, with an optimum at pH 11.0. The optimum temperature for
      the purified enzyme was 60 degrees C. The activity of the enzyme was totally lost
      in the presence of PMSF, suggesting that the purified enzyme is a serine
      protease. The kinetic constants K (m) and K (cat) of the purified enzyme using N
      succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide were 0.158 mM and 1.14 x 10(5)
      min(-1), respectively. The catalytic efficiency (K (cat) /K (m)) was 7.23 x 10(8)
      min(-1) M(-1). The enzyme showed extreme stability toward non-ionic surfactants
      and oxidizing agents. In addition, it showed high stability and compatibility
      with some commercial liquid and solid detergents. The aprJ1 gene, which encodes
      the alkaline protease from V. metschnikovii J1, was isolated, and its DNA
      sequence was determined. The deduced amino acid sequence of the preproenzyme
      differs from that of V. metschnikovii RH530 detergent-stable protease by 12 amino
      acids, 7 located in the propeptide and 5 in the mature enzyme.

PMID- 19390885
TI  - Early succession of bacterial biofilms in paper machines.
AB  - Formation of biofilms causes severe problems in paper machines, and hence
      financial costs. It would be preferable to prevent attachment of the primary
      colonizing bacteria than to control the growth of secondary communities, which
      are sheltered by exopolysaccharide slime layers. We have therefore investigated
      the early succession of paper-machine biofilms by incubating stainless-steel test
      coupons in the process water-flow lines in two paper machines operating in
      slightly alkaline conditions in temperatures (45 and 49 degrees C) supporting
      thermophilic microbes. Microbial succession was profiled using length
      heterogeneity analysis of PCR-amplified 16S rRNA genes (LH-PCR) and linking the
      sequence data of the created 16S rRNA gene libraries to the dominant LH-PCR
      peaks. Although the bacterial fingerprints obtained from the attached surface
      communities varied slightly in different samples, the biomarker signals of the
      dominating primary-colonizing bacterial groups remained high over time in each
      paper machine. Most of the 16S rRNA gene copies in the early biofilms were
      assigned to the genera Rhodobacter, Tepidimonas, and Cloacibacterium. The
      dominance of these sequence types decreased in the developing biofilms. Finally,
      as phylogenetically identical primary-colonizers were detected in the two
      different paper mills, the machines evidently had similar environmental
      conditions for bacterial growth and potentially a common source of contamination.

PMID- 19390886
TI  - Monitoring the survival of islet transplants by MRI using a novel technique for
      their automated detection and quantification.
AB  - OBJECT: There is a clinical need to be able to assess graft loss of transplanted
      pancreatic islets (PI) non-invasively with clear-cut quantification of islet
      survival. We tracked transplanted PI in diabetic mice during the early post
      transplant period by magnetic resonance imaging (MRI) and quantified the islet
      loss using automatic segmentation technique. MATERIALS AND METHODS: Magnetically
      labeled islet iso-, allo- and xenografts were injected into the right liver
      lobes. Animals underwent MRI scanning during 14 days after PI transplantation. MR
      images were processed using custom-made software, which automatically detects
      hypointense regions representing PI. It is based on morphological top-hat and
      bottom-hat transforms. RESULTS: Manually and automatically detected areas,
      corresponding to PI, differed by 4% in phantoms. Signal loss regions due to PI
      decreased comparably in all groups during the first week post transplant.
      Throughout the second week post-transplant, the signal loss area continued in a
      steep decline in case of allografts and xenografts, whereas the decline in case
      of isografts slowed down. CONCLUSION: Automatic segmentation allows for the more
      reproducible, objective assessment of transplanted PI. Quantification confirms
      the assumption that a significant number of islets are destroyed in the first
      week following transplantation irrespective of allografts, xenografts or
      isografts.

PMID- 19390887
TI  - Detection and quantification of D-glucuronic acid in human bile using 1H NMR
      spectroscopy: relevance to the diagnosis of pancreatic cancer.
AB  - OBJECTIVE: There are no specific biomarkers available for the definitive
      diagnosis of pancreatic cancer. Analysis of D-glucuronic acid (GlcUA) in bile
      could be valuable in this regard. MATERIALS AND METHODS: Bile samples obtained
      from patients with pancreatic cancer (n = 4), chronic pancreatitis (n = 3) and
      control patients with biliary obstruction (n = 10) were analyzed by (1)H NMR
      spectroscopy. GlcUA was quantified from the peak area of the alpha-(1)CH signal
      (at 5.24 ppm) obtained by deconvolution. RESULTS: GlcUA was detected in human
      bile by one-dimensional (1)H NMR and two-dimensional (1)H-(1)H COSY and TOCSY
      experiments. Quantification of GlcUA was achieved by measuring the peak area of
      the alpha-(1)CH signal using CPMG experiment, and the quantities of GlcUA were
      calibrated to account for the attenuation due to T (2) relaxation. GlcUA was
      observed at elevated levels in bile samples obtained from pancreatic cancer
      patients, whereas it was either absent or found in negligible amounts in control
      and chronic pancreatitis patients. The reason for the presence of elevated levels
      of GlcUA could be the hydrolysis of biliary bilirubin diglucuronide by beta
      glucuronidase, released excessively from pancreatic tissue during the course of
      malignancy. CONCLUSION: Analysis of D-glucuronic acid in bile could be valuable
      in the detection of pancreatic cancer, and detecting GlcUA by in vivo (1)H MRS
      has the potential to help in the non-invasive diagnosis of pancreatic cancer.
      Given that only four cancer patients have been studied so far, the new biomarker
      is regarded as a preliminary finding, but one that warrants further
      investigation.

PMID- 19390888
TI  - Interaction of nano-TiO2 with lysozyme: insights into the enzyme toxicity of
      nanosized particles.
AB  - BACKGROUND, AIM, AND SCOPE: Nanomaterials have been used increasingly in
      industrial production and daily life, but their human exposure may cause health
      risks. The interactions of nanomaterial with functional biomolecules are often
      applied as a precondition for its cytotoxicity and organ toxicity where various
      proteins have been investigated in the past years. In the present study, nano
      TiO(2) was selected as the representative of nanomaterials and lysozyme as a
      representative for enzymes. By investigating their interaction by various
      instrumentations, the objective is to identify the action sites and types,
      estimate the effect on the enzyme structure and activity, and reveal the toxicity
      mechanism of nanomaterial. MATERIALS AND METHODS: Laboratory-scale experiments
      were carried out to investigate the interactions of nano-TiO(2) with lysozyme.
      The interaction of nano-TiO(2) particles with lysozyme has been studied in the
      analogous physiological media in detail by UV spectrometry, fluorophotometry,
      circular dichroism (CD), scanning electron microscope, zeta-potential, and laser
      particle size. RESULTS: The interaction accorded with the Langmuir isothermal
      adsorption and the saturation number of lysozyme is determined to be 580 per nano
      TiO(2) particle (60 nm of size) with 4.7 x 10(6) M(-1) of the stability constant
      in the physiological media. The acidity and ion strength of the media obviously
      affected the binding of lysozyme. The warping and deformation of the lysozyme
      bridging were demonstrated by the conversion of its spatial structure from alpha
      helix into a beta-sheet, measured by CD. In the presence of nano-TiO(2), the
      bacteriolysis activity of lysozyme was subjected to an obvious inhibition.
      DISCUSSION: The two-step binding model of lysozyme was proposed, in which
      lysozyme was adsorbed on nano-TiO(2) particle surface by electrostatic
      interaction and then the hydrogen bond (N-H...O and O-H...O) formed between nano
      TiO(2) particle and polar side groups of lysozyme. The adsorption of lysozyme
      obeyed the Langmuir isothermal model. The binding of lysozyme is dependent on the
      acidity and ion strength of the media. The bigger TiO(2) aggregate was formed in
      the presence of lysozyme where lysozyme may bridge between nano-TiO(2) particles.
      The coexistence of nano-TiO(2) particles resulted in the transition of lysozyme
      conformation from an alpha-helix into a beta-sheet and a substantial inactivation
      of lysozyme. The beta-sheet can induce the formation of amyloid fibrils, a
      process which plays a major role in pathology. CONCLUSIONS: Lysozyme was adsorbed
      on the nano-TiO(2) particle surface via electrostatic attraction and hydrogen
      bonds, and they also bridged among global nano-TiO(2) particles to form the
      colloidal particles. As a reasonable deduction of this study, nano-TiO(2) might
      have some toxic impacts on biomolecules. Our data suggest that careful attention
      be paid to the interaction of protein and nanomaterials. This could contribute to
      nanomaterial toxicity assessment. RECOMMENDATIONS AND PERSPECTIVES: Our results
      strongly suggest that nano-TiO(2) has an obvious impact on biomolecules. Our data
      suggest that more attention should be paid to the potential toxicity of nano
      TiO(2) on biomolecules. Further research into the toxicity of nanosized particles
      needs to be carried out prior to their cell toxicity and tissue toxicity. These
      investigations might serve as the basis for determining the toxicity and
      application of nanomaterials.

PMID- 19390889
TI  - [Networking--for the benefit of the patient!].

PMID- 19390890
TI  - [Telemedicine in Germany: status, chances and limits].
AB  - In Germany there are many successful special applications of telemedicine.
      However, these projects are generally not extendable to the whole nation because
      of the highly complex German health care system, limited funding, heterogeneous
      IT standards in ambulatory and hospital care, insufficient official electronic
      health card use, the different data protection and privacy regulations of the
      federal and state governments, doubts of physicians and patients as well as
      unequal costs and benefits for the various persons involved in telemedicine.
      These problems can be overcome by better legal regulations for a seamless
      interaction of ambulatory and hospital care, improved IT standards and support of
      the interoperability of telemedical and other health care IT, adaption of the
      health care organization, work flow and reimbursement of telemedicine services,
      better information and education of all persons involved about the necessity and
      limits of telemedicine. There are no doubts about the benefits of telemedicine
      but to achieve these advantages for the whole healthcare system in Germany
      requires much work, time and good will.

PMID- 19390891
TI  - Maximal tongue strength in typically developing children and adolescents.
AB  - Evaluating tongue function is clinically important as the generation of adequate
      pressure by the anterior tongue against the hard palate is crucial for efficient
      oropharyngeal swallowing. Research in the evaluation of tongue function in
      pediatric populations is limited due to questions about the reliability of
      children's performance on objective measures of tongue strength and the lack of
      comparative data from typically developing children. The present study examined
      tongue strength in 150 children and adolescents, 3-16 years of age, with no
      history of speech or swallowing disorders using the Iowa Oral Pressure Instrument
      (IOPI). Children as young as 3 years of age were able to tolerate the IOPI
      standard tongue bulb and were reliable performers on measures of tongue strength
      with an unconstrained mandible. Tongue strength measurements were elicited in
      blocks of three trials with a 30-s rest between the trials and a 20-min rest
      between blocks. Tongue strength increased with age with no consistent best trial
      across ages and participants. Males showed a slight increase in tongue strength
      over females at ages 14 and 16. This study suggests maximum pediatric tongue
      strength may be reliably evaluated using commercially available equipment and
      provides a limited sample comparative database.

PMID- 19390892
TI  - Patient dose during videofluoroscopy swallowing studies in a Hong Kong public
      hospital.
AB  - A videofluoroscopy swallowing study (VFSS) is a major tool in diagnosing
      swallowing disorders. Like all other medical examinations that involve
      irradiation, patient dosage is a major concern. Cerebrovascular accident (CVA)
      and nasopharyngeal carcinoma (NPC) have been two of the most common indicating
      pathologies for VFSS studies. The goals of this study were to determine the mean
      dose area product (DAP) value and fluoroscopic time for VFSS examinations in Tuen
      Mun Hospital, to compare the result with the dose reference level of other
      similar studies, and to document the results with respect to the various common
      indicating pathologies for VFSS (i.e., CVA, NPC). Three hundred ninety-eight VFSS
      exams were performed at our center in a 24-month period; the mean DAP was 2.42 +/
      2.04 Gy cm(2) for an effective dose of 0.31 +/- 0.26 mSv. The mean fluoroscopic
      time is 4.23 +/- 2.56 min. The P value of 0.0034 was obtained using the Kruskal
      Wallis test to compare the DAP from various groups of indicating pathologies. It
      suggests that there are significant differences in dosage between CVA and NPC
      patients and the entire population. We conclude that the dose of radiation
      received by a patient undergoing a VFSS examination in our center was comparable
      to the international standard and that of other similar studies. We can also
      conclude that there is a significant difference in dosage between NPC and CVA
      patients and the overall population suggesting that the indicating pathologies
      for a VFSS have certain effects on the resulting irradiating dose delivered but
      more studies have to be done to explain such differences.

PMID- 19390893
TI  - Effects of oropharyngeal air-pulse stimulation on swallowing in healthy older
      adults.
AB  - While previous research has shown that air-pulse stimulation of the oropharynx
      facilitates saliva swallowing in young adults, the effects of air pulses in older
      adults have not been examined. Responses to air-pulse stimulation may differ in
      young and older adults given age-related changes in sensation, swallowing
      physiology, and swallow-related brain activation. Therefore, this study sought to
      determine the effects of oropharyngeal air-pulse stimulation on saliva swallowing
      rates in 18 healthy older adults. Saliva swallowing rates were monitored across
      six conditions: baseline without mouthpiece, baseline with mouthpiece in situ,
      unilateral right oropharyngeal stimulation, unilateral left oropharyngeal
      stimulation, bilateral oropharyngeal stimulation, and sham stimulation. Results
      indicated that bilateral oropharyngeal air-pulse stimulation was associated with
      a statistically significant increase in mean saliva swallowing rate compared to
      baseline without mouthpiece, baseline with mouthpiece in situ, and sham
      stimulation. In previous studies, young adults reported an irrepressible urge to
      swallow in response to oropharyngeal air-pulse delivery, but the older adults in
      the current study did not perceive the air-pulse stimulation as being associated
      with swallowing or other behaviors. These findings indicate that oropharyngeal
      air-pulse stimulation facilitates the elicitation of saliva swallowing in older
      adults.

PMID- 19390894
TI  - Comparison of urinary scents of two related mouse species, Mus spicilegus and Mus
      domesticus.
AB  - Whereas the house mouse (Mus domesticus) has been studied extensively in terms of
      physiology/behavior and pheromonal attributes, the evolutionarily related mound
      building mouse (Mus spicilegus) has received attention only recently due to its
      divergent behavioral traits related to olfaction. To date, no chemical studies on
      urinary volatile compounds have been performed on M. spicilegus. The rationale
      for our investigations was to determine if there are differences in urinary
      volatiles of intact and castrated M. spicilegus males and to explore further
      whether this species could utilize the same or structurally similar pheromones as
      the male house mouse, M. domesticus. The use of capillary gas chromatography/mass
      spectrometry (GC-MS) together with sorptive stir bar extraction sampling enabled
      quantitative comparisons between the intact and castrated M. spicilegus urinary
      profiles. Additionally, through GC-MS and atomic emission (sulfur-selective)
      detection, we identified qualitative molecular differences between intact M.
      spicilegus and M. domesticus. A series of volatile and odoriferous lactones and
      the presence of coumarin were the unique features of M. spicilegus, as was the
      notable absence of 2-sec-butyl-4,5-dihydrothiazole (a prominent M. domesticus
      male pheromone) and other sulfur-containing compounds. Castration of M.
      spicilegus males eliminated several substances, including delta-hexalactone and
      gamma-octalactone, and substantially decreased additional compounds, suggesting
      their possible role in chemical communication. Some other M. domesticus pheromone
      components were also found in M. spicilegus urine. These comparative chemical
      analyses support the notion of metabolic similarities as well as the uniqueness
      of some volatiles for M. spicilegus, which may have a distinct physiological
      function in reproduction and behavior.

PMID- 19390895
TI  - Defense by volatiles in leaf-mining insect larvae.
AB  - The defense strategy of an insect toward natural enemies can include a trait that
      appears at first sight to contradict its defensive function. We explored
      phylogeny, chemistry, and defense efficiency of a peculiar group of hymenopteran
      sawfly larvae where this contradiction is obvious. Pseudodineurini larvae live in
      leaf mines that protect them from some enemies. Disturbed larvae also emit a
      clearly perceptible lemon-like odor produced by ventral glands, although the mine
      hampers the evaporation of the secretion. The mine could also lead to
      autointoxication of a larva by its own emitted volatiles. Citral was the major
      component in all Pseudodineurini species, and it efficiently repels ants. We
      conclude that full-grown larvae that leave their mine to pupate in the soil
      benefit from citral by avoiding attacks from ground-dwelling arthropods such as
      ants. In some species, we also detected biosynthetically related compounds, two 8
      oxocitral diastereomers (i.e., (2E,6E)- and (2E,6Z)-2,6-dimethylocta-2,6
      dienedial). Synthetic 8-oxocitral proved to be a potent fungicide, but not an ant
      repellent. The discrete distribution of 8-oxocitral was unrelated to species
      grouping in the phylogenetic tree. In contrast, we discovered that its presence
      was associated with species from humid and cold zones but absent in species
      favoring warm and dry environments. The former should be protected by 8-oxocitral
      when faced with a fungal infestation while crawling into the soil. Our work shows
      the importance of integrating knowledge about behavior, morphology, and life
      history stages for understanding the complex evolution of insects and especially
      their defense strategies.

PMID- 19390897
TI  - Mechanism and behavioral context of male sex pheromone release in Nasonia
      vitripennis.
AB  - Males of the parasitic wasp Nasonia vitripennis (Hymenoptera: Pteromalidae)
      attract virgin females by releasing a sex pheromone composed of (4R,5R)- and
      (4R,5S)-5-hydroxy-4-decanolide (HDL). The pheromone is biosynthesized in the
      rectal vesicle of males. In the present study, we investigated the mechanism and
      behavioral context of pheromone release, and determined the range of activity and
      the longevity of the chemical signal. Our data show that the sex pheromone of N.
      vitripennis is substrate-borne and is deposited on surfaces by dabbing movements
      of the abdominal tip, a behavior previously described in N. vitripennis males as
      'abdomen dipping'. Chemical markings deposited by a single male were highly
      attractive to virgin females. Chemical analyses revealed the presence of HDL in
      surface washings of marked areas, and HDL amounts correlated with male marking
      activity. Pheromone deposition occurred spontaneously without any additional cues
      being present, but marking intensity increased greatly after copulation or after
      a single contact with a virgin female. In contrast, marking intensity was not
      influenced by the presence of host puparia. Male pheromone deposits were
      perceived by females in a still-air olfactometer at distances of up to 4.5 cm and
      remained attractive for at least 2 h. The function of the substrate-borne sex
      pheromone is discussed with respect to the mating system of N. vitripennis.

PMID- 19390898
TI  - Altered olfactory receptor neuron responsiveness is correlated with a shift in
      behavioral response in an evolved colony of the cabbage looper moth, Trichoplusia
      ni.
AB  - There is little understanding of how sex pheromone blends might change during
      speciation events. For the cabbage looper, Trichoplusia ni, there is a mutant
      laboratory strain that has exhibited characteristics of a shift to a new
      pheromone blend. Mutant females produce a blend that is significantly different
      from wild-type females in having a much higher proportion of a minor pheromone
      component and lower quantity of the major component. Males in this colony have
      changed over the years to become more broadly tuned and fly upwind equally well
      to both the wild-type and mutant female pheromone blends. They also exhibit
      reduced overall sensitivity to pheromone, flying upwind to either blend at a
      lower success rate than is typical when wild-type males respond to the wild-type
      blend. Using single-cell recordings, we examined the olfactory receptor neurons
      (ORNs) of males from evolved and wild-type colonies for evidence of changes in
      response characteristics that might explain the above-described behavioral
      evolution. We found that in evolved-colony males the ORNs tuned to the major sex
      pheromone component exhibited a somewhat lower responsiveness to that compound
      than the ORNs of wild-type males. In addition, the minor pheromone component,
      emitted at excessively high rates by mutant females, elicited a drastically
      reduced ORN responsiveness in evolved-colony males compared to wild-type males.
      This alteration in ORN responsiveness may be responsible for allowing evolved
      males to tolerate the excessive amounts of the minor pheromone component in the
      mutant female blend, which would normally antagonize the upwind flight of
      unevolved males. Thus, peripheral olfactory alterations have occurred in T. ni
      males that are correlated with the evolution of the more broadly tuned, but less
      sensitive, behavioral response profile.

PMID- 19390899
TI  - Video-assisted skin-sparing breast-conserving surgery for breast cancer and
      immediate reconstruction with autologous tissue: clinical outcomes.
AB  - BACKGROUND: This study analyzed clinical results of video-assisted breast
      conserving surgery for breast cancer. METHODS: Video-assisted breast-conserving
      surgery is indicated for breast cancer that has not invaded the skin. A skin
      incision is made at an inconspicuous site. Skin-sparing partial mastectomy was
      performed endoscopically on 244 patients (stage I, n = 94; stage II, n = 150).
      Morbidity, curability, and patient satisfaction were analyzed. RESULTS: Skin
      necrosis was seen in nine patients. Local recurrence was seen in 13 patients
      (mean postoperative interval 65.3 months). Distant metastasis-free survival at 60
      months was 93.6% for stage I and 90.5% for stage II. Overall survival was 95.7%
      for stage I and 96.9% for stage II. Satisfaction with surgery as investigated by
      questionnaire was "good" for 72.3% of patients. CONCLUSIONS: Video-assisted
      breast-conserving surgery showed no increases in local or distant recurrence and
      patient satisfaction was high. Video-assisted breast-conserving surgery appears
      useful for local treatment of breast cancer.

PMID- 19390900
TI  - Combined modality treatment of resectable and borderline resectable pancreas
      cancer: expert consensus statement.

PMID- 19390901
TI  - Pretreatment assessment of resectable and borderline resectable pancreatic
      cancer: expert consensus statement by Callery et al.

PMID- 19390902
TI  - Physician response to "by-the-way" syndrome in primary care.
AB  - BACKGROUND/OBJECTIVE: "By-the-way" syndrome, a new problem raised by the patient
      at an encounter's closure, is common, but little is known about how physicians
      respond when it occurs. We analyzed the content of the syndrome, predictors of
      its appearance, and the physician response. DESIGN/PARTICIPANTS: Cross-sectional
      study of 92 videotaped encounters in an academic primary care clinic. RESULTS:
      The syndrome occurred in 39.1% of observed encounters. Its major content was bio
      psychosocial (39%), psychosocial (36%), or biomedical (25%), whereas physician
      responses were mostly biomedical (44%). The physician response was concordant
      with the patient's question in 61% of encounters if the content of the question
      was psychosocial, 21% if bio-psychosocial, and 78% if biomedical; 32% of
      physicians solicited the patient's agenda two times or more in the group without,
      versus 11% in the group with, the syndrome (P = 0.02). In 22% of the encounters,
      physicians did not give any answer to the patient's question, particularly
      (38.5%) if it was of psychosocial content. CONCLUSIONS: "By-the-way" syndrome is
      mainly bio-psychosocial or psychosocial in content, whereas the physician
      response is usually biomedical. Asking about the patient's agenda twice or more
      during the office visit might decrease the appearance of this syndrome.

PMID- 19390904
TI  - What sense can the sense-making perspective make for economics?
AB  - A landscape of interdisciplinary decision theories is sketched with a tentative
      place for the sense-making approach presented by Salvatore et al (2009).
      Uncertainty and ambiguity are highlighted as key concepts in both, economics and
      sense-making perspectives aligning possible and useful conceptual coincidences
      among post Keynesian economics (Shackle 1974; Davidson 2005) cultural psychology
      (Salvatore et al. 2009) and organization theory (March 1978, 1994; Weick 1995).
      Few ideas for the construction of possible research agenda aimed to build a
      complex model of decision making are suggested. Finally a brief reflection on the
      study of underground economy is presented. The challenge for the link between
      psychology and economics is to figure out a descriptive general model of the
      process of decision making, perhaps by combining weighted elements of the
      different ways in which human rationality emerges--calculation, rule following,
      sense-making--for explaining singular and specific decisions.

PMID- 19390903
TI  - Peer assessment of professionalism: a five-year experience in medical clerkship.
AB  - INTRODUCTION: Faculty assessment of students' professionalism is often based upon
      sporadic exposure to students. Peers are in a unique position to provide valid
      judgments of these behaviors. AIMS: (1) To learn if peer assessments of
      professional conduct correlate with traditional performance measures; (2) to
      determine if peer assessments of professionalism influence the designation of
      honors, and (3) to explore student and faculty opinions regarding peer
      assessment. SETTING: Internal Medicine Clerkship at Southern Illinois University.
      PROGRAM DESCRIPTION: Since 2001 anonymous student peer assessments of
      professionalism have been used in assigning clerkship grades. PROGRAM EVALUATION:
      Peer assessments of professionalism had weak, though significant, correlations
      with faculty ratings (r = 0.29), performance on the NBME subject test (r = 0.28),
      and performance on a cumulative performance assessment (r = 0.30), and did not
      change the total number of honors awarded. A majority of students (71%) felt
      comfortable evaluating their peers, and 77% would keep the peer evaluation
      procedure in place. A majority of faculty (83%) indicated that peer assessments
      added valuable information. DISCUSSION: Peer assessments of professional conduct
      have little correlation with other performance measures, are more likely to have
      a positive influence on final clerkship grades, and have little impact on
      awarding honors.

PMID- 19390905
TI  - Hand-mixed and premixed antibiotic-loaded bone cement have similar homogeneity.
AB  - Since low-dose antibiotic-loaded bone cement (ALBC) was approved by the FDA for
      second-stage reimplantation after infected arthroplasties in 2003, commercially
      premixed low-dose ALBC has become available in the United States. However,
      surgeons continue to mix ALBC by hand. We presumed hand-mixed ALBC was not as
      homogeneous as commercially premixed ALBC. We assessed homogeneity by determining
      the variation in antibiotic elution by location in a batch, from premixed and
      hand-mixed formulations of low-dose ALBC. Four hand-mixed methodologies were
      used: (1) suspension--antibiotic powder in the liquid monomer; (2) no-mix-
      antibiotic powder added but not mixed with the polymer powder before adding
      monomer; (3) hand-stirred--antibiotic powder stirred into the polymer powder
      before the monomer was added; and (4) bowl-mix--antibiotic powder mixed into
      polymer powder using a commercial mixing bowl before the monomer was added.
      Antibiotic elution was measured using the Kirby-Bauer bioassay. None of the
      mixing methods had consistently dissimilar homogeneity of antibiotic distribution
      from the others. Based upon our data we conclude hand-mixed low-dose ALBC is not
      less homogeneous than commercially premixed formulations.

PMID- 19390907
TI  - Successful treatment of severe juvenile microscopic polyangiitis with rituximab.
AB  - Microscopic polyangiitis (MPA) previously called hypersensitivity angiitis is a
      systemic necrotizing vasculitis affecting predominantly small vessels. MPA
      involves multiple organ systems including the lung, the kidneys, the joints, and
      the skin. MPA mostly affects adults in their fourth and fifth decade of life. MPA
      and Wegener;s granulomatosis are grouped together as ANCA-associated vasculitis.
      MPA is associated with high titre of myeloperoxidase antineutrophil cytoplasmic
      antibodies (MPO)-ANCA. We present a 14-year-old female patient presented with
      MPA. She was treated with steroids and cyclophosphamide. After the complication
      of severe lung involvement, rituximab was administered as immune-modulating
      treatment. The MPA came to remission. This is the first report of a pediatric
      patient with MPA treated with rituximab. Rituximab might be a potential
      therapeutic option for relapsing ANCA associated vasculitis in childhood.

PMID- 19390910
TI  - Visual representation of National Institute of Allergy and Infectious Disease and
      Food Allergy and Anaphylaxis Network criteria for anaphylaxis.
AB  - We present a user-friendly visual representation of The National Institute of
      Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network
      criteria so as to enhance recognition of anaphylaxis and active teaching and
      learning.

PMID- 19390908
TI  - Undifferentiated connective tissue disease: a seven-center cross-sectional study
      of 184 patients.
AB  - The purpose of this study was to characterize the clinical and serological
      features of a large cohort of patients with antinuclear antibody (ANA) positive
      undifferentiated connective tissue disease (UCTD). Consecutive patients with
      UCTD, followed up at the Rheumatology Clinic of the participating centers, were
      included. Data from these patients were obtained by clinical evaluation and chart
      review. All patients were diagnosed as having UCTD on basis of the following
      criteria: positive ANA plus at least one clinical feature of connective tissue
      disease, but not fulfilling classification criteria for any differentiated
      connective tissue disease. One hundred eighty-four patients were studied (female
      patients-94.5%; mean age at time of evaluation-47 years). The most prevalent
      manifestations were arthralgia (66%), arthritis (32%), Raynaud's phenomenon
      (30%), sicca symptoms (30%), and leukopenia (19%). The prevalence of ANA was
      100%, anti-SSA 20%, anti-dsDNA 14%, and anti-SSB 7%. Patients with anti
      dsDNA/anti-Sm, anticentromere/anti-Scl70, or anti-SSA/anti-SSB antibodies more
      frequently presented a set of manifestations close to systemic lupus
      erythematosus (SLE), systemic sclerosis, or Sjogren syndrome, respectively. We
      analyze a large cohort of UCTD. Seventy-two percent of these UCTD patients
      present lupus-, scleroderma-, or Sjogren-like features but do not fulfill
      classification criteria and mostly present a mild disease.

PMID- 19390911
TI  - Comparison of the characteristics and outcome among patients suffering from out
      of-hospital primary cardiac arrest and drowning victims in cardiac arrest.
AB  - BACKGROUND: In 2003, the International Liaison Committee on Resuscitation (ILCOR)
      published the Recommended Guidelines for Uniform Reporting of Data from Drowning:
      the "Utstein style" ("Utstein Style for Drowning," USFD) to improve the
      understanding of epidemiology, treatment, and outcome prediction after drowning.
      AIMS: The aim of this study was to compare the characteristics and outcome
      between patients suffering from out-of-hospital primary cardiac arrest (OHPCA)
      and drowning victims in cardiac arrest (DCA) by analysis of variables based on
      the USFD. METHODS: All cases of OHPCA and DCA from February 1998 to February 2007
      were included in the research and analysis. Data on OHPCA and DCA patients were
      collected using the Utstein method. Data on DCA patients were then compared with
      data of OHPCA patients. RESULTS: During the study period 788 cardiac arrests with
      resuscitation attempts were identified: 528 of them were OHPCA (67%) and 32 (4%)
      were DCA. The differences between DCA and OHPCA patients were: the DCA patients
      were younger (46.5 +/- 21.4 vs 62.5 +/- 15.8; p = 0.01), suffered a witnessed
      cardiac arrest less frequently (9/32 vs 343/528; p = 0.03), were more often found
      in a nonshockable rhythm (29/32 vs 297/528; p < 0.0001), had a prolonged
      ambulance response time (11 vs 6 min; p = 0.001), had a relatively better (but
      not statistically significant) return of spontaneous circulation (ROSC) in the
      field [22/32 (65%) vs 301/528 (57%); p = 0.33], more of them were admitted to
      hospital [19/32 (60%) vs 253/528 (48%); p = 0.27], and also had a significantly
      higher survival rate (discharge from hospital) [14/32 (44%) vs 116/528 (22%); p =
      0.01]. DCA patients had higher values of initial PETCO(2) (53.2 +/- 16.8 vs 15.8
      +/- 8.3 mmHg; p < 0.0001) and average PETCO(2) (43.5 +/- 13.8 vs 23.5 +/- 8.2; p
      = 0.002). These values of PETCO(2) suggest an asphyxial mechanism of cardiac
      arrest. The analysis showed that DCA patients who survived were younger, had more
      bystander cardiopulmonary resuscitation (CPR), shorter call-arrival interval,
      higher values of PETCO(2) after 1 min of CPR, higher average and final values of
      PETCO(2), lower value of initial serum K+, and more of them received vasopressin
      (p < 0.05) in comparison with DCA patients who did not survive. CONCLUSION: DCA
      patients had a better survival rate (discharge from hospital), higher initial and
      average PETCO(2) values, and more of them had nonshockable initial rhythm.
      Survival (discharge from hospital) in DCA patients is associated with the
      PETCO(2) values, initial serum K+ values, administration of vasopressin, and
      ambulance response time.

PMID- 19390912
TI  - Efficacy and compliance of a prehospital spinal immobilization guideline.
AB  - BACKGROUND: Prehospital spinal immobilization criteria are useful in identifying
      those at risk for spinal fractures, while reducing the number of patients
      unnecessarily immobilized. The use of immobilization criteria, without regard to
      mechanism of injury, has been shown to accomplish this task. AIMS: The study's
      purpose is to examine efficacy of a prehospital spinal clearance guideline and
      triage/management of these injuries. METHODS: This was a retrospective study of
      traumatically injured patients based on a clinical clearance spinal
      immobilization guideline between January 2006 and January 2007. Two gold
      standards were used in the analysis (radiographic findings and physician
      clearance without radiographs). This project was approved by the Mayo Clinic
      Institutional Review Board. RESULTS: The study included 942 patients documented
      to have a traumatic injury. Of these, 43 (4.6%) had an acute spinal fracture. The
      guideline allowed 558 (59.2%) patients to be cleared, and 1.3% (7/558) had
      fractures. The remaining 384 did not meet clearance criteria and accounted for 36
      (9.4%, 36/384) fractures. The guideline correctly predicted 36 of 43 fractures.
      The median age of the 7 fractures not immobilized was 82 years and of the 36
      patients with fractures that were immobilized was 48 years. When immobilization
      was indicated, caregivers were 77.6% (298/384) compliant. Of the noncompliant
      22.4% (86/384) there were 9 fractures. CONCLUSIONS: This spinal guideline
      demonstrates efficacy in identifying those at risk for spinal fractures. An age
      extreme criteria may enhance this already effective guideline. Further analysis
      of compliance failures may improve the guideline's ability for fracture
      prediction.

PMID- 19390913
TI  - A comparison of emergency department utilization by elderly and younger adult
      patients presenting to three hospitals in Hong Kong.
AB  - BACKGROUND: The elderly population is increasing in absolute and relative terms
      in most developed countries, and this is protected to have a major impact on the
      delivery of health care, particularly acute and emergency services. The aim of
      this study is to describe the pattern of utilization of emergency department (ED)
      services in Hong Kong by the elderly and to compare it to the utilization by
      younger adults. METHODS: Data on ED visits to three acute hospitals in the
      eastern New Territories were retrieved from a central computerized database of ED
      attendances. Data on all adult patients (aged > or =15 years) who attended the
      three EDs in 2006 were analyzed retrospectively. Patients aged 15 to 64 years
      were defined as younger adults; patients aged > or =65 years were defined as
      elderly. The attendance rate, ED consultation process, hospital admission rate
      and disease pattern of the two age groups were compared. RESULTS: Elderly
      patients required significantly more emergency care resources than younger
      adults. Elderly ED patients were brought to hospital more frequently by ambulance
      (42.8% vs. 14.8%, p < 0.0001) and required hospital admission more often (45.0%
      vs. 15.5%, p < 0.0001) than younger adults. A significantly higher proportion of
      elderly patients were triaged as being in the critical, emergency or urgent
      categories compared to younger adults (44.4% vs. 18.2%, p < 0.0001). Laboratory
      tests, radiography and CT scanning were performed on elderly patients more
      frequently than on younger adults (p < 0.0001), and their lengths of stay in EDs
      and emergency wards were significantly longer (p < 0.0001). Neurological symptoms
      and chest pain were the most common presenting symptoms in elderly ED patients.
      CONCLUSION: With the foreseeable rapid growth of the elderly population, ED
      utilization by the elderly will increase. Health service delivery, including that
      in the ED, needs to take account of the specific features and requirements of the
      elderly population in each locale.

PMID- 19390914
TI  - Demographics of toxic exposures presenting to three public hospital emergency
      departments in Singapore 2001-2003.
AB  - BACKGROUND: The demographics of poisoned patients and the circumstances of toxic
      exposure have not been evaluated in Singapore for the last 10 years. AIM: This
      study aims to give an estimate of the burden of poisoning in Singapore from the
      emergency department's (ED) perspective. METHOD: A retrospective study of toxic
      exposure was conducted over a period of 3 years from 2001 to 2003 at the ED of
      three public hospitals, one being a paediatric hospital. RESULTS: There were
      9,212 cases of toxic exposures during the study period, which constituted 0.94%
      of total ED attendances. The poison exposure rate was 1.7 per 1,000 population
      and the estimated case fatality rate was 0.8 per 1,000 ED attendances for
      poisoning. The mean age of patients was 29 years and the majority were male
      (63.3%). Non-accidental injuries constituted 60% of the cohort. Alcohol was the
      commonest toxin involved (26%), but paracetamol (acetaminophen) was the most
      common pharmaceutical agent (33%). The mean time of exposure to ED presentation
      was 3.3 h. About one third of the patients were admitted of whom 157 patients
      (4.7% of admitted cases) required intensive care management. CONCLUSION: The
      patients were predominantly young adults. This may suggest a need for poison
      prevention and chemical safety education to reduce the impact on this high-risk
      group. Although poisoning accounts for only 1% of the total ED attendance, a
      sizable proportion of them required inpatient care (36.1%) with a significant
      proportion requiring intensive care management. However, it was also noted that a
      third of those who were admitted stayed for less than 24 h, and hence a short
      stay ward in the ED might be a cost-effective strategy to consider.

PMID- 19390915
TI  - Does implementation of a paediatric asthma clinical practice guideline worksheet
      change clinical practice?
AB  - BACKGROUND: Despite the development of evidence-based practice guidelines in many
      countries for asthma treatment in children, there is limited evidence that using
      such guidelines improves patient care. AIMS: Our aim was to evaluate whether the
      implementation of an evidence-based asthma clinical practice guideline (CPG)
      worksheet changes clinical practice. METHODS: The study was a before and after
      study of the implementation of a paediatric asthma CPG in a tertiary paediatric
      emergency department (ED). All children aged 2-16 years who had a diagnosis of
      asthma were included. Clinical data were obtained by retrospective chart review
      for time periods before (May to September 2003) and after (May to September 2005)
      the introduction of the CPG worksheet. Primary outcomes were: use of spacers for
      salbutamol instead of nebulisers, use of ipratropium and use of corticosteroids.
      Secondary outcomes were use of an ED action plan, ordering chest X-rays (CXR) and
      admission rate. RESULTS: Before implementation, 240 children presented with
      asthma and after implementation, 286 children presented. The two groups had
      similar ages, asthma severity, admission respiratory rate (RR) and oxygen
      saturation. Following implementation there was an increase in spacer use from 17
      to 26% [+9%; 95% confidence interval (CI): 2-16%; p = 0.015] and a reduction in
      ipratropium use from 58 to 44% (-13%; 95% CI: -22 to -5%; p = 0.0029). The
      proportion of patients treated with corticosteroids did not change. The number of
      patients with an ED action plan increased. The number of CXR ordered decreased
      and the hospital admission rate decreased. CONCLUSIONS: The study demonstrates
      that implementation of an asthma CPG worksheet in a tertiary paediatric ED
      resulted in modest changes in clinical practice, mainly by increasing clinician
      adherence to the guidelines.

PMID- 19390916
TI  - The design and pilot of a translation aid to help ED clinicians enhance
      communication with the Portuguese-speaking patient.
AB  - BACKGROUND: Language barriers hinder health care delivery in settings with
      culturally diverse populations. Interventions to accommodate non-English-speaking
      patients have been shown to shorten length of stay and reduce non-urgent visits.
      AIMS: Our aim was to design and do a pilot study on an instrument to facilitate
      history taking with Portuguese-speaking patients in the emergency department
      (ED). METHODS: An instrument was designed to facilitate history taking with
      Portuguese-speaking patients (PSPs). A pocket-sized document incorporated,
      bilingual, problem-oriented, closed-ended questions for common ED presentations
      as well as numbers, measurements of time, and anatomy. A paired audio tutorial on
      a compact disk (CD) demonstrated correct pronunciation of each phrase. A 3-month
      pilot was undertaken in a downtown teaching hospital on a convenience sample of
      PSPs who indicated the need for a translator at triage. A trained Portuguese
      speaking observer monitored clinician/patient pairs using the instrument and
      scored differential patient comprehension in a standardized manner. Qualitative
      patient and clinician impressions were assessed. A follow-up survey assessed
      emergency physician (EP) impressions of the instrument. RESULTS: Eight of nine
      eligible clinician/patient pairs were enrolled. The average proportions of
      questions answered appropriately in English and then using the instrument were
      16.7% and 85.5%, respectively, with mean improvement of 68.8% (confidence
      interval: 45.6-92.1). Most (7/8) patients agreed that the instrument had helped
      in communication. Half (4/8) of the clinicians indicated that the tool had helped
      them communicate, and most (7/8) indicated that they would use the instrument in
      the future. Few (2/17) physicians utilized the audio guide. Suggested
      modifications included incorporation of phonetics. CONCLUSIONS: The pilot of the
      instrument was well received by patients and resulted in improved communication.

PMID- 19390917
TI  - Thiopentone sedation for sedation of acutely agitated, violent, intoxicated
      patients: evaluation of 2 cases.
AB  - Two cases of violent, drug-intoxicated patients who presented considerable
      problems in management, and were resistant to standard sedative agents, are
      described. Effective and safe sedation, without the need for full anaesthesia and
      endotracheal intubation, was achieved using titrated doses of thiopentone. The
      merits of selecting this agent in these circumstances are discussed.

PMID- 19390918
TI  - Subtalar dislocation: rare and often forgotten.

PMID- 19390919
TI  - A dusky hand-expect the unexpected.

PMID- 19390920
TI  - Lateral lumbar spondyloptosis.

PMID- 19390921
TI  - Comment on Grmec et al.: a treatment protocol including vasopressin and
      hydroxyethyl starch solution is associated with increased rate of return of
      spontaneous circulation in blunt trauma patients with pulseless electrical
      activity.

PMID- 19390924
TI  - Toward a new level of international exchange of information about gastric cancer
      research: a message from a new editor-in-chief.

PMID- 19390925
TI  - Joint international efforts to combat a still-deadly disease: the next
      generation.

PMID- 19390926
TI  - Improving outcome for scirrhous gastric cancer.

PMID- 19390927
TI  - Imaging in assessing lymph node status in gastric cancer.
AB  - BACKGROUND: Accurate assessment of lymph node status is of crucial importance for
      appropriate treatment planning and determining prognosis in patients with gastric
      cancer. The aim of this study was to systematically review the current role of
      imaging in assessing lymph node (LN) status in gastric cancer. METHODS: A
      systematic literature search was performed in the PubMed/MEDLINE and Embase
      databases. The methodological quality and diagnostic performance of the included
      studies was assessed. RESULTS: Six abdominal ultrasonography (AUS) studies, 30
      endoscopic ultrasonography (EUS) studies, 10 multidetectorrow computed tomography
      (MDCT) studies, 3 conventional magnetic resonance imaging (MRI) studies, 4 (18)F
      fluoro-2-deoxyglucose positron emission tomography (FDG-PET) studies, and 1 FDG
      PET/CT fusion study were included. In general, the included studies had moderate
      methodological quality. The sensitivity and specificity of AUS varied between
      12.2% and 80.0% (median, 39.9%) and 56.3% and 100% (median, 81.8%). The
      sensitivity and specificity of EUS varied between 16.7% and 95.3% (median, 70.8%)
      and 48.4% and 100% (median, 84.6%). The sensitivity and specificity of MDCT
      varied between 62.5% and 91.9% (median, 80.0%) and 50.0% and 87.9% (median,
      77.8%). The sensitivity and specificity of MRI varied between 54.6% and 85.3%
      (median, 68.8%) and 50.0% and 100% (median, 75.0%). The sensitivity and
      specificity of FDG-PET varied between 33.3% and 64.6% (median, 34.3%) and 85.7%
      and 97.0% (median, 93.2%). The sensitivity and specificity of the FDG-PET/CT
      fusion study were 54.7% and 92.2%. For all the imaging modalities, there were no
      significant differences between the mean sensitivities and specificities of high-
      and low-quality studies. CONCLUSION: AUS, EUS, MDCT, conventional MRI, and FDG
      PET cannot reliably be used to confirm or exclude the presence of LN metastasis.
      The performance of highresolution PET/CT fusion and functional MRI techniques
      still has to be determined.

PMID- 19390928
TI  - Study of clinicopathological factors associated with the occurrence of
      synchronous multiple gastric carcinomas.
AB  - BACKGROUND: Multiple gastric carcinomas often arise in gastric mucosa with
      chronic gastritis, particularly severe intestinal metaplasia. In regard to such
      characteristics, several clinicopathological risk factors for multiple carcinomas
      have been reported, but no clinically useful criteria are available at present
      for assessing the onset of multiple gastric carcinomas. If the risk for multiple
      gastric carcinomas could be accurately assessed, efficient and accurate
      surveillance could be performed following minimally invasive therapies. METHODS:
      In the present study, we investigated clinicopathological differences between 94
      cases of multiple early gastric carcinomas and 285 cases of solitary early
      gastric carcinoma. We tested 379 specimens of gastric carcinomas that had been
      surgically resected at the Department of General and Gastroenterological Surgery
      of Osaka Medical College, Japan, from April 1999 to December 2006. RESULTS:
      Univariate analysis of clinicopathological factors in the present study showed
      that multiple gastric carcinomas were significantly correlated to old age (> or
      =65 years), well- and moderately differentiated histological type, mucin
      phenotype (intestinal type), distribution of atrophic mucosa in the stomach
      (severe), degree of intestinal metaplasia in the surrounding mucosa (severe), and
      heterotopic glandular cysts. Multivariate analysis using the stepwise method
      identified age (> or =65 years) and degree of intestinal metaplasia in the
      surrounding mucosa (severe) as significant independent risk factors for multiple
      gastric carcinomas. CONCLUSION: While other studies have shown risk factors for
      multiple gastric carcinomas, the present study is unique in showing risk
      assessment criteria based on a combination of risk factors for multiple gastric
      carcinomas.

PMID- 19390929
TI  - Impact of plasma tissue inhibitor of metalloproteinase-1 on long-term survival in
      patients with gastric cancer.
AB  - BACKGROUND: The expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) is
      correlated with tumor invasion and metastases. METHODS: The plasma TIMP-1
      concentration was examined preoperatively in 149 patients with gastric cancer who
      underwent a surgical resection. The cutoff value of TIMP-1 was set at 112.5 ng/ml
      based on a previous report. These patients were followed up for more than 5 years
      prospectively. RESULTS: Plasma TIMP-1 was positive in 30 of the 149 patients
      (20.1%). The overall survival rate was 78.2% at 5 years in patients with negative
      plasma TIMP-1, while this rate was 26.7% at 5 years in patients with positive
      plasma TIMP-1. By univariate analyses, T, N, M, and R category, and TIMP-1, were
      significant prognosticators. Multivariate analyses demonstrated T, N, and TIMP-1
      to be significant prognosticators. The survival curve was clearly separated with
      respect to TIMP-1. CONCLUSION: These results suggest that plasma TIMP-1 is a
      strong independent prognosticator for the long-term survival of patients with
      gastric cancer.

PMID- 19390930
TI  - Phase II trial of S-1 for neoadjuvant chemotherapy against scirrhous gastric
      cancer (JCOG 0002).
AB  - BACKGROUND: The prognosis of scirrhous gastric cancer remains poor despite
      extended surgery or adjuvant or neoadjuvant chemotherapy. A pilot study of S-1
      (TS-1; Taiho Pharmaceutical, Tokyo, Japan), an oral 5-fluorouracil derivative,
      for neoadjuvant chemotherapy unexpectedly showed good response and a promising
      effect on survival. Therefore, the Japan Clinical Oncology Group conducted a
      phase II trial to confirm the efficacy of S-1 for neoadjuvant chemotherapy
      against resectable scirrhous gastric cancer. METHODS: Patients were eligible if
      they had typical scirrhous gastric cancer invading more than half of the stomach,
      and resectable disease confirmed by laparoscopic staging. The treatment schedule
      consisted of two courses (each, 4-week administration and 2-week withdrawal) of S
      1 (100-120 mg/body per day), followed by radical surgery. RESULTS: Fifty-five
      eligible patients were registered. Three completed only one course of the
      neoadjuvant chemotherapy, whereas 52 completed two courses. Toxicity was
      acceptable, with a few grade 3 (5.5%) events, but no grade 4 adverse events. The
      response rate was 32.6% in 43 evaluable patients. Of the 55 patients, 2 refused
      operation, 1 developed lung metastasis, and 52 underwent laparotomy. The curative
      resection rate was 80.8%, with acceptable morbidity and no mortality. The
      survival curve at 2 years' follow up showed a better survival rate than that of
      the historical controls, but did not reach the expected survival rate.
      CONCLUSION: S-1 neoadjuvant chemotherapy appeared feasible and showed positive
      effects against scirrhous gastric cancer; however, the survival rate with S-1 did
      not reach the expected rate required when selecting an agent for a phase III
      trial to confirm the effectiveness of neoadjuvant chemotherapy against scirrhous
      gastric cancer.

PMID- 19390931
TI  - Expression of tight-junction-associated proteins in human gastric cancer:
      downregulation of claudin-4 correlates with tumor aggressiveness and survival.
AB  - BACKGROUND: Claudin, occludin, and zonula occludens (ZO)-1 are known as tight
      junction-associated proteins. The aim of this study was to examine the expression
      of these proteins in gastric carcinoma. METHODS: Gastric cancer tissues (n = 124)
      were obtained from 124 patients who underwent gastrectomy at our hospital between
      January 2000 and December 2004. The expression of the above tight-junction
      associated proteins in carcinoma, normal mucosa, and metaplastic epithelium was
      examined using immunohistochemistry. In addition, the expression of claudin-4
      mRNA was examined in fresh frozen tissue obtained from 34 patients. RESULTS:
      Significant correlations were seen between the expression of claudin-4, occludin,
      and ZO-1. In regard to claudin-4, significant correlations were seen between the
      expression of claudin-4 evaluated by immunohistochemistry and the expression of
      claudin-4 mRNA. Claudin-4 expression was significantly decreased in tumors with
      undifferentiated-type adenocarcinoma, advanced T stage, lymph node metastasis,
      and peritoneal metastasis. Occludin and ZO-1 expression was significantly
      decreased in tumors with undifferentiated-type adenocarcinoma. Overall survival
      was significantly shorter in patients with low claudin-4 expression. Cox
      multivariate analysis revealed that low claudin-4 expression was independently
      associated with significantly decreased overall survival. CONCLUSION: Tight
      junction-associated proteins, particularly claudin-4, may play important roles in
      determining invasiveness, metastatic potential, and survival in gastric cancer.

PMID- 19390932
TI  - A comparison of gastric cancer between Japan and China.

PMID- 19390933
TI  - Modified Billroth-I reconstruction after distal gastrectomy.

PMID- 19390934
TI  - The first European Union Network of Excellence for Gastric Cancer conference,
      Rome, Italy, April 2008.

PMID- 19390936
TI  - Implementation and limitations of meta-analysis of randomized trials from the
      clinical biostatistician's point of view.

PMID- 19390937
TI  - Efficacy of adjuvant chemotherapy using tegafur-based regimen for curatively
      resected gastric cancer: update of a meta-analysis.
AB  - A consensus regarding standard adjuvant chemotherapy for curatively resected
      gastric cancer has not been obtained between Japan and the Western world. In
      order to evaluate the effect of a tegafur-based regimen (the most frequently used
      regimen in Japan) compared with a surgery-alone control, a meta-analysis was
      performed, investigating four clinical trials. After meticulous examination of
      each trial, trials with improper noncentralized randomization were excluded from
      the analysis. A total of 1197 patients were enrolled in the four relevant trials
      determined to be eligible for the meta-analysis (Nakajima 1984; Japan Clinical
      Oncology Group [JCOG] 8801, JCOG 9206-2, and National Surgical Adjuvant Study of
      Gastric Cancer [NSASGC], in which a tegafur-based regimen was used for
      chemotherapy and central randomization was performed. The endpoint was overall
      survival, and a common hazard ratio was estimated. The 5-year overall survival
      rates differed among the trials because of differences in the background disease
      status. But there was no heterogeneity (P = 0.235) of treatment effect. The
      estimated common hazard ratio was 0.75, with a 95% confidence interval of 0.58
      0.98. The treatment effect of the tegafur-based agent was shown to be
      statistically significant (P = 0.037) compared with surgery-alone therapy (n =
      1179). From the results of the above meta-analysis, it is suggested that
      chemotherapy with a tegafur-based agent after surgery can improve the survival of
      patients with curatively resected gastric cancer. The Global Advanced/Adjuvant
      Stomach Tumor Research through International Collaboration (GASTRIC) group is
      conducting two individual patient data meta-analyses, testing post-operative
      adjuvant chemotherapy for resect-able gastric cancer and chemotherapy for
      advanced gastric cancer. It is expected to determine and quantify the role of
      adjuvant chemotherapy in detail from the GASTRIC.

PMID- 19390938
TI  - The role of meta-analysis in cancer clinical trials.
AB  - Meta-analysis of randomized controlled trials is considered to be the methodology
      that provides the most solid scientific basis for constructing clinical
      guidelines. It involves systematically collecting the results of similar studies
      that were conducted to verify similar medical hypotheses and combining these
      results statistically. In meta-analysis, targeting only those randomized
      controlled trials with good comparability also provides the meta-analysis with
      comparability. With the combining of multiple studies and the increased sample
      size, meta-analysis provides results with higher clarity than those obtained from
      a single study. In conventional meta-analyses, in addition to estimating the
      combined effect, the cause of heterogeneity of the effects among studies is
      usually explored. If multiple studies reveal homogeneous effects, the overall
      effect is interpretable and generalizability can be suggested; that is, the
      results can be reproducible even when the study conditions are slightly modified.
      On the other hand, if the effect cannot be viewed as homogeneous among the
      studies, it is difficult to interpret the overall effect obtained from a meta
      analysis. From the viewpoints of clarity, comparability, and generalizability,
      meta-analysis and large-scale clinical trials can provide the most valuable
      evidence among several possible study designs. In this article, the role of meta
      analysis in cancer clinical trials is illustrated with the example of adjuvant
      therapy with UFT in patients with curatively resected rectal cancer, compared
      with the example of a large-scale clinical trial using oxaliplatin, fluorouracil,
      and leucovorin as adjuvant treatment for colon cancer.

PMID- 19390939
TI  - Contributions of meta-analyses based on individual patient data to therapeutic
      progress in colorectal cancer.
AB  - Meta-analysis is the statistical process of combining information from several
      studies addressing the same question. Meta-analyses based on individual patient
      data are far more reliable and informative than those based on summary statistics
      obtained from the trialists or extracted from the published literature. Meta
      analysis of randomized clinical trials may contribute to therapeutic progress
      through (1) establishing efficacy benefits beyond a reasonable doubt, (2)
      identifying sources of heterogeneity between trials, (3) studying subsets
      reliably, (4) confirming differences in toxicity profiles, (5) evaluating the
      cost-effectiveness of experimental therapies, (6) assessing surrogate endpoints,
      and (7) addressing ancillary questions. All of these potential contributions are
      illustrated with examples in early and advanced colorectal cancer.

PMID- 19390940
TI  - Meta-analysis for the evaluation of surrogate endpoints in cancer clinical
      trials.
AB  - The identification and validation of putative surrogate endpoints in oncology is
      a great challenge to medical investigators, statisticians, and regulators. A
      putative surrogate endpoint must be validated at both individual-level and trial
      level before it can be used to replace the clinical endpoint in a future clinical
      trial. Recently, meta-analytic methods for evaluating potential surrogates have
      become widely accepted in cancer clinical trials. In this review, after
      addressing multiple complications and general issues surrounding surrogate
      endpoints, we review various proposed and adopted meta-analytic methodologies
      pertaining to the application of these methods to oncology clinical trials with
      different tumor types. In oncology, several applications have successfully
      identified useful surrogates. For example, disease-free survival and progression
      free survival have been validated through meta-analyses as acceptable surrogates
      for overall survival in adjuvant colon cancer and advanced colorectal cancer,
      respectively. We also discuss several limitations of surrogate endpoints,
      including the critical issues that the extrapolation of the validity of a
      surrogate is always context-dependent and that such extrapolation should be
      exercised with caution.

PMID- 19390941
TI  - A literature review of molecular markers predictive of clinical response to
      cytotoxic chemotherapy in patients with breast cancer.
AB  - BACKGROUND: We aimed to identify, through a review of the literature, candidate
      genes for a prospective predictive chemosensitivity test in patients with breast
      cancer. METHODS: Papers demonstrating an association between gene alterations in
      tumor tissue and clinical chemosensitivity in breast cancer patients were
      selected by Medline searches. We calculated odds ratios (ORs) and their 95%
      confidence intervals (CIs) of response rates for patients who had tumors with or
      without gene alteration. Combined ORs and CIs were estimated using the
      DerSimonian-Laird method. RESULTS: A total of 18 genes were evaluated for
      association with clinical chemosensitivity in 6378 patients registered in 69
      studies. The median (range) number of patients in each study was 73 (29-319).
      Overexpression of ABCB1 (P-glycoprotein) was associated with poor responses to
      first-line chemotherapy (combined OR [CI], 0.16 [0.05-0.59]; n = 322).
      Overexpression and amplification of TOP2A (topoisomerase II-alfa) were more
      frequently observed in patients who responded to first-line chemotherapy
      (combined OR [CI], 2.73 [1.02-7.27]; n = 323). Overexpression of ERBB2 (c-erbB2)
      was associated with favorable responses in patients treated with both first-line
      anthracycline-based chemotherapy and second-line taxane-based chemotherapy
      (combined ORs [CIs], 1.60 [1.19-2.17]; n = 1807 and 2.24 [1.06-4.74]; n = 259,
      respectively). BCL2 overexpression was associated with resistance to first-line
      chemotherapy (combined OR [CI], 0.44 [0.21-0.91]; n = 816). CONCLUSION: ABCB1,
      TOP2A, ERBB2, and BCL2 were good candidates for future clinical trials of
      predictive chemosensitivity tests in patients with breast cancer.

PMID- 19390942
TI  - Chemo-hyperthermic peritoneal perfusion (CHPP) for appendiceal pseudomyxoma
      peritonei.
AB  - BACKGROUND: Pseudomyxoma peritonei is derived mostly from the rupture of an
      appendiceal cystic tumor and produces a large quantity of mucinous substance.
      Though its malignancy level is low, radical resection is difficult and its
      prognosis is poor. In some institutes in European countries and the United
      States, multidisciplinary treatment with chemo-hyperthermia at a relatively low
      temperature is performed following subtotal peritonectomy. We carried out high
      temperature chemo-hyperthermic peritoneal perfusion following incomplete
      resections of mucinous tumors in six patients. METHODS: After resection of the
      main tumor and macroscopic gross tumor resection of dissemination, heated
      perfusate containing anticancer agents was poured into the peritoneal cavity and
      stirred and pumped into a circulation between the abdomen and a reservoir. The
      temperature of the surface of the peritoneum was maintained at around 43 degrees
      C. RESULTS: The intraperitoneal space was sufficiently heated without severe
      complications. The pathological diagnosis in four of the patients was peritoneal
      mucinous carcinomatosis, and in the other two patients, it was intermediate type
      between peritoneal mucinous carcinomatosis and disseminated peritoneal
      adenomucinosis. Two patients died, 15 and 26 months after the treatment. The
      other four patients have survived for 4, 24, 26, and 80 months now, and two of
      them, who have survived for 26 and 80 months, received a second treatment 18 and
      32 months, respectively, after the initial treatment. These results seemed not to
      be inferior to those in the reports from institutes in Europe and the United
      States which performed subtotal peritonectomy and then used mild hyperthermia in
      chemo-hyperthermia. CONCLUSION: For treating pseudomyxoma peritonei, high
      temperature chemo-hyperthermic peritoneal perfusion following incomplete tumor
      resection is effective even without peritonectomy.

PMID- 19390943
TI  - Phase I study of amrubicin and vinorelbine in non-small cell lung cancer
      previously treated with platinum-based chemotherapy.
AB  - BACKGROUND: Combination chemotherapy comprising amrubicin and vinorelbine as a
      second-line therapy for advanced non-small cell lung cancer (NSCLC) has not been
      fully evaluated. To determine the maximum tolerated dose (MTD) and recommended
      dose (RD), the present phase I study examined patients with advanced NSCLC.
      METHODS: The subjects were nine patients with histologically confirmed advanced
      NSCLC, Eastern Cooperative Oncology Group performance status 0-1, prior platinum
      based first-line chemotherapy, and measurable or evaluable lesions. Treatment
      consisted of five dose levels, with amrubicin 35-45 mg/m2 administered as a 5-min
      intravenous infusion on days 1-3 and vinorelbine 15-25 mg/m2 given as a 1-h
      intravenous infusion on days 1 and 8, every 3 weeks. RESULTS: All patients had
      received carboplatin and paclitaxel as first-line therapy. Dose-limiting toxicity
      (DLT) was seen in two of six patients (febrile neutropenia and deep vein
      thrombosis ) at level 1, allowing us to conduct level 2. At level 2, all three
      patients experienced DLT (leucopenia > or =4 days in one patient; febrile
      neutropenia in three patients; and infection in two patients), and this level was
      determined as the MTD. Subsequently, level 1 (amrubicin 35 mg/m2 and vinorelbine
      15 mg/m2) was defined as the RD. Responses in the nine patients included a
      partial response in one patient and stable disease in four patients. CONCLUSION:
      As second-line therapy, the RD of the combination of amrubicin and vinorelbine is
      35 mg/m2 and 15 mg/m2, respectively. Further study should proceed to clarify the
      efficacy of this regimen.

PMID- 19390944
TI  - Intermittent docetaxel therapy with estramustine for hormone-refractory prostate
      cancer in Japanese patients.
AB  - BACKGROUND: We evaluated the efficacy and toxicity of intermittent docetaxel
      (DCT) with estramustine (EM) for hormone-refractory prostate cancer (HRPC).
      METHODS: Fifteen patients were enrolled. They received injected DCT (70 mg/m2
      body surface) on day 1 in association with oral EM 560 mg/day (days 1-5).
      Treatments were repeated every 3 weeks. Serum prostate-specific antigen (PSA)
      levels were categorized based on the first three courses. Patients exhibiting
      either a response or stable disease (SD) could have a holiday from treatment
      (intermittent schedule). The holiday continued until elevation of the PSA level
      from the nadir baseline level occurred three times. All patients were evaluated
      for toxicity and quality of life (QOL). Survival curves were established using
      Kaplan-Meier graphs. RESULTS: The median number of courses of DCT/EM therapy was
      five (range, 3-12 courses). The response rate of the first cycle was 53%: 3
      patients with complete response (CR), 5 patients with partial response (PR), 4
      patients with SD, and 3 patients with disease progression. Eight patients were
      able to begin the second re-entry cycle. No patients showed a CR, 2 patients
      exhibited PR, 4 patients had SD, and the overall response rate was 25%. The
      survival rates were 93% at 1 year, and 26.1% at 2 years Grade 3-4 anemia was
      observed in 2 patients (13.3%), neutropenia in 11 (73.3%), and thrombocytopenia
      in 2 (13.3%). The QOL scale showed good QOL after 6 months, with improvement in
      the score for nausea and vomiting. CONCLUSION: Intermittent DCT/EM therapy was
      well tolerated, and has the potential to prolong survival, with a high QOL, in
      patients with HRPC.

PMID- 19390946
TI  - Sunitinib-resistant gastrointestinal stromal tumors harbor cis-mutations in the
      activation loop of the KIT gene.
AB  - BACKGROUND: Although sunitinib malate has shown significant clinical effect on
      imatinib-resistant gastrointestinal stromal tumors, with acceptable tolerability
      and improved prognosis for the patients, the mechanism of resistance to the drug
      is still under investigation. METHODS: We analyzed findings in 8 patients (seven
      men and one woman, median age, 59 years) out of 17 patients with imatinib
      resistant gastrointestinal stromal tumors who had been treated with sunitinib.
      Sunitinib was orally administered once a day at a starting dose of 37.5 mg/day,
      50 mg/day, or 75 mg/day, with 4 weeks on and 2 weeks off. RESULTS: All imatinib-
      as well as sunitinib-resistant lesions showed viable tumor cells strongly re
      expressing the KIT protein. Pre-imatinib samples had heterogeneous KIT mutations
      either in exon 9 (n = 1) or exon 11 (n = 7), and seven imatinib-resistant tumors
      carried a secondary mutation either in the ATP-binding domain or in the
      activation loop in the same allele as the primary mutation. Most patients with
      imatinib-resistant tumors carrying secondary mutations in the ATP-binding domain
      obtained clinical benefits from sunitinib, whereas some tumors with mutations in
      the activation loop showed resistance to the drug. A tumor with mutations in exon
      11 and 13 of the KIT gene, and showing partial response to sunitinib, harbored a
      third mutation in the activation loop when sunitinib resistance was shown. All
      additional secondary and tertiary mutations were located on the same allele as
      the primary mutation (cis-mutation). CONCLUSION: These findings indicate that an
      additional cis-mutation in the activation loop of the KIT gene could be a
      potential cause of sunitinib resistance in gastrointestinal stromal tumors.

PMID- 19390947
TI  - Standardized uptake value on FDG-PET as a marker for disease activity in patients
      with non-Hodgkin's lymphoma: comparison with serum soluble interleukin-2 receptor
      values.
AB  - BACKGROUND: We compared standardized uptake values (SUVs) on positron emission
      tomography with a glucose analog, 2-[F-18] fluoro-2-deoxy-D-glucose (FDG-PET) and
      serum soluble interleukin-2 receptor (sIL-2R) values in patients with non
      Hodgkin's lymphoma (NHL) in the pre-, mid- (after three or four cycles), and post
      treatment periods of chemotherapy (pre, mid, and post, respectively), and we
      examined whether the SUV was a useful tumor marker for NHL. METHODS: The SUVs on
      PET and sIL-2R values were retrospectively evaluated based on all the clinical
      information available in 40 patients (31 in pre, 24 in mid, and 24 in the post
      periods). Patients in complete remission status were classified as group A and
      those with active residual disease in the mid and post periods were classified as
      group B. RESULTS: In pre, the SUV and sIL-2R values exhibited sensitivity of 100%
      and 84%, respectively. In mid, the SUV was lower in group A than in group B,
      while sIL-2R was not different. The SUV yielded better specificity than sIL-2R
      (88% vs. 25%, respectively), though the difference was not significant. In mid,
      the SUV in patients later assigned to group A in post was lower than than the SUV
      in group B, whereas sIL-2R was not different. In post, the specificity and
      accuracy of SUV were better than those of sIL-2R (95 vs. 47%, and 96 vs. 58%,
      respectively). Both the SUV and sIL-2R were lower in group A than in group B.
      CONCLUSION: The SUV on PET was better than the serum sIL-2R as a marker to
      evaluate the disease status of NHL, and was considered to be a useful tumor
      marker for NHL.

PMID- 19390945
TI  - UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by
      irinotecan in Japanese cancer patients.
AB  - BACKGROUND: Gene polymorphisms of the UDP-glucuronosyltransferase 1 family,
      polypeptide A1 (UGT1A1) contribute to individual variations in adverse events
      among patients administered irinotecan, and the distribution of the polymorphisms
      shows large interethnic differences. Variation in the solute carrier organic
      anion-transporter family, member 1B1 (SLCO1B1) gene also has a significant effect
      on the disposition of irinotecan in Asian cancer patients. In the present study,
      we evaluated the association of genetic polymorphisms of UGT1A1 and SLCO1B1 with
      irinotecanrelated neutropenia in Japanese cancer patients. METHODS: One hundred
      and thirty-five consecutive patients treated with irinotecan were enrolled.
      Genotypes of UGT1A1 (*60, *28, *6, and *27) and SLCO1B1 (*1b, *5, and haplotype
      *15) were determined by direct sequencing. Severe neutropenia refers to events
      observed during the first cycle of irinotecan treatment. RESULTS: Severe
      neutropenia was observed in 29 patients (22%). Six patients were homozygous and
      48 heterozygous for UGT1A1*6. Only 1 patient was homozygous for UGT1A1*28.
      Homozygosity for UGT1A1*6 was associated with a high risk of severe neutropenia
      (odds ratio [OR], 7.78; 95% confidence interval [CI], 1.36 to 44.51). No
      significant association was found between severe neutropenia and other UGT1A1
      polymorphisms or SLCO1B1 polymorphisms. CONCLUSION: These findings suggest that
      the UGT1A1*6 polymorphism is a potential predictor of severe neutropenia caused
      by irinotecan in Japanese cancer patients.

PMID- 19390948
TI  - An atypical extrahepatic metastasis of the distal phalanx from hepatocellular
      carcinoma.
AB  - A 49-year-old woman presented with severe swelling and pain of the left little
      finger, which had exacerbated rapidly, in October 2006. The patient had a history
      of hepatocellular carcinoma and metastatic lung cancer. She had undergone partial
      hepatectomy for the hepatocellular carcinoma in September 2001 and pulmonary
      resection for metastatic lung cancer in November 2005. Roentgenogram of the hand
      on admission showed complete destruction of the distal phalanx of the left little
      finger. The final pathological result of the tissue obtained by disarticulation
      was an extrahepatic metastasis of hepatocellular carcinoma. Extrahepatic
      metastasis from primary hepatocellular carcinoma to the hand is very rare and
      only four cases have been reported in the literature. All the patients with
      extrahepatic metastases from the primary hepatocellular carcinoma to the hand had
      poor prognoses, but the patient presented in this article exhibited an unusual
      clinical course. The patient is still alive 1 year after the diagnosis of
      extrahepatic bone metastasis of the distal phalanx.

PMID- 19390949
TI  - Primary osteosarcoma of ovary.
AB  - Primary osteosarcoma originating from the ovary is an exceedingly rare, highly
      malignant tumor. Only a few cases have been reported in the past few decades. We
      describe a 50-year-old postmenopausal woman who presented with a large abdominal
      mass. The clinical diagnosis was malignant ovarian cancer. Her disease was
      aggressive; she had no response to systemic chemotherapy and died within 1 month
      of presentation. A definitive diagnosis of primary ovarian osteosarcoma was made
      by histopathological examination of autopsy specimens. Although rare, primary
      ovarian osteosarcoma should be considered in the differential diagnosis of a
      large, rapidly progressing pelvic mass in a postmenopausal woman. Early diagnosis
      provides hope of a complete surgical resection, which is currently the only
      promising treatment.

PMID- 19390950
TI  - Adenoendocrine cell carcinoma of the gallbladder clinically mimicking squamous
      cell carcinoma.
AB  - We present the case of a 62-year-old Japanese man whose histological diagnosis
      was adenoendocrine cell carcinoma of the gallbladder at autopsy, but whose
      antemortem diagnosis was squamous cell carcinoma. The patient was admitted to
      hospital with complaints of occasional vomiting and abdominal pain. Abdominal
      computed tomography revealed a large tumor on the gallbladder involving the
      adjacent liver, colon, and duodenum, with multiple metastases in the greater
      omentum and paraportal lymph nodes. The serum level of squamous cell carcinoma
      antigen (SCCA) was high, whereas that of carbohydrate antigen (CA) 19-9, as well
      as that of carcinoembryonic antigen (CEA) was within the normal range. Due to
      these clinical features, we first suspected advanced squamous cell carcinoma of
      the gallbladder. After two cycles of gemcitabine monotherapy, the tumor had
      become enlarged and the regimen was changed to a combination of docetaxel and
      cisplatin. Though tumor regression was achieved and his serum SCCA level
      normalized after 3 months, the patient rejected additional chemotherapy and died
      8 months after the diagnosis. The histopathological findings made by autopsy
      demonstrated the tumor to be an adenoendocrine cell carcinoma without squamous
      carcinoma cells. The case is interesting in that the clinical features were
      similar to those of squamous cell carcinoma of the gallbladder.

PMID- 19390951
TI  - Extremely acute exacerbation of interstitial pneumonia after interferon-alpha
      treatment for metastatic renal cell carcinoma.
AB  - We report the case of a 62-year-old Japanese man who presented with right renal
      cell carcinoma and multiple metastases. The patient had a past medical history of
      idiopathic interstitial pneumonia 6 years previously. He had received pulse
      corticosteroid therapy and oral prednisolone, which resulted in marked clinical
      improvement. He had been followed up for the interstitial pneumonia, without
      medication, for 5 years and the idiopathic interstitial pneumonia was inactive
      when the metastatic renal cell carcinoma was diagnosed. However, the patient
      presented with extremely acute exacerbation of the interstitial pneumonia that
      occurred after only three intramuscular injections of standard-dose interferon
      alpha. Urologists should be aware of this complication in the treatment of renal
      cell carcinoma patients who have a prior history of interstitial pneumonia.

PMID- 19390952
TI  - A dedifferentiated liposarcoma of the anterior mediastinum.
AB  - Dedifferentiated liposarcoma was first described in 1979, and its definition has
      been recently extended. We found an undiagnosed anterior mediastinal mass in a 56
      year-old man for whom we performed a complete tumor resection through median
      sternotomy. Microscopic examination revealed that the mass was primarily a low
      grade, dedifferentiated liposarcoma, with a partial high-grade area. Occurrence
      of dedifferentiated liposarcoma in the anterior mediastinum is rare. We did not
      perform any adjuvant therapy. Three years after the surgery, the patient is alive
      without disease. In lipoma-like, well-differentiated liposarcoma cases, we should
      consider the possibility of dedifferentiated liposarcoma if a mild, atypical
      spindle cell component is found.

PMID- 19390953
TI  - Alpha and beta noradrenergic mediation of NMDA glutamatergic effects on lordosis
      behaviour and plasmatic LH concentrations in the primed female rat.
AB  - In previous studies we have found that blockade of NMDA (N-Methyl-D-Aspartic
      Acid)-type glutamatergic receptor with intracerebroventricular (ICV) selective
      drugs induces an inhibition of lordosis in ovariectomized (OVX) estrogen primed
      rats receiving progesterone or luteinizing hormone releasing hormone (LHRH). By
      the opposite way, stimulation with NMDA in OVX estrogen primed rats induced a
      significant increase of lordosis. In the present study the action of an alpha1
      noradrenergic antagonist, HEAT (BE 2254/2-beta-4-Hydroxyphenyl-Ethyl-Aminomethyl
      1-Tetralone), and Metoprolol, a beta-noradrenergic antagonist, were studied
      injecting them ICV previously to NMDA administration in treated OVX estrogen
      primed rats. In experiment 1, the enhancing effect on lordosis induced by NMDA at
      high dose (1 microg) was abolished by HEAT administration (P < 0.001 for 3 and 6
      microg), and the LH plasma levels were decreased only with the higher dose (P <
      0.05), suggesting that behavioral effects are quite more sensitive to the alpha
      blockade than hormonal effects. In experiment 2, enhancing effects on lordosis
      behavior were not observed with neither the NMDA at low dose (0.5 microg) nor the
      metoprolol alone (5.71 microg), but a synergism was observed when both were
      simultaneously administered (P < 0.001). The LH plasma levels were increased by
      Metoprolol alone (P < 0.05), and powered by the combination with NMDA at low dose
      (P < 0.01 vs. SAL and NMDA alone); no differences were observed with Metoprolol.
      LH increase was observed with Metoprolol even without behavioural modifications.
      These findings strongly suggest that facilitatory and inhibitory effects of NMDA
      in this model are mediated by alpha- and beta-adrenergic transmission in both,
      behavioral and hormonal effects.

PMID- 19390954
TI  - The Nm23-H1-h-Prune complex in cellular physiology: a 'tip of the iceberg'
      protein network perspective.
AB  - Nm23-H1 (also known as NDPKA) and h-Prune form a protein complex that is part of
      a little-understood protein network. Modifications of this complex correlate with
      cancer status. Here, we focus on the role of the Nm23-H1-h-Prune complex in
      cellular physiology, through an analysis of the balance between the 'bound' and
      'non-bound' states of Nm23-H1 and h-Prune, whereby we speculate on the 'read-out'
      during cell homeostasis under non-balanced conditions. We have analysed the
      biochemical activities of both Nm23-H1 and h-Prune alone and in combination,
      focussing on the anti-metastatic activity of Nm23-H1. We have then investigated
      the cellular mechanisms responsible for the formation of the Nm23-H1-h-Prune
      complex. To evaluate the importance of the equilibrium between the formation of
      the Nm23-H1-h-Prune complex and the 'free' levels of Nm23-H1 and h-Prune, we
      propose a model based on a pro-cancer condition where this equilibrium is
      negatively affected.

PMID- 19390955
TI  - Regulation of mitochondrial Ca2+ and its effects on energetics and redox balance
      in normal and failing heart.
AB  - Ca(2+) has been well accepted as a signal that coordinates changes in cytosolic
      workload with mitochondrial energy metabolism in cardiomyocytes. During increased
      work, Ca(2+) is accumulated in mitochondria and stimulates ATP production to
      match energy supply and demand. The kinetics of mitochondrial Ca(2+)
      ([Ca(2+)](m)) uptake remains unclear, and we review the debate on this subject in
      this article. [Ca(2+)](m) has multiple targets in oxidative phosphorylation
      including the F1/FO ATPase, the adenine nucleotide translocase, and Ca(2+)
      sensitive dehydrogenases (CaDH) of the tricarboxylic acid (TCA) cycle. The well
      established effect of [Ca(2+)](m) is to activate CaDHs of the TCA cycle to
      increase NADH production. Maintaining NADH level is not only critical to keep a
      high oxidative phosphorylation rate during increased cardiac work, but is also
      necessary for the reducing system of the cell to maintain its reactive oxygen
      species (ROS) -scavenging capacity. Further, we review recent data demonstrating
      the deleterious effects of elevated Na(+) in cardiac pathology by blunting
      [Ca(2+)](m) accumulation.

PMID- 19390956
TI  - Emotional intelligence: painting different paths for low-anxious and high-anxious
      psychopathic variants.
AB  - Psychopathic individuals may be disaggregated into low-anxious (emotionally
      stable "primary psychopaths") and high-anxious (emotionally disturbed "secondary
      psychopaths") variants that may differ in their capacity for adaptive behavior.
      In turn, the skills encompassed by emotional intelligence (EI) predict social and
      business success. Based on a sample of 188 male undergraduates, we evaluate the
      performance of low-anxious psychopathic, high-anxious psychopathic, and low
      psychopathic comparison groups on a measure of EI. High-anxious psychopaths
      manifested significantly lower EI than the other two groups, particularly with
      respect to managing emotions and facilitating thoughts. In contrast, low-anxious
      psychopaths manifested intact EI, with skill in facilitating thoughts. High
      anxious (but not low anxious) psychopaths were more likely than low psychopathic
      comparisons to manifest violence. These results are consistent with the notion
      that primary psychopaths have greater capacity to attain success in traditional
      society than secondary psychopaths, and invite a direct test of this hypothesis
      in future research.

PMID- 19390957
TI  - Subject of the year: remote monitoring.

PMID- 19390958
TI  - Developing a clinical assessment model suited to use in an agency providing short
      term substance use treatment: findings from a delphi survey of expert opinion.
AB  - This paper presents findings from a Delphi survey of expert opinion asking
      participants (n = 18), all recruited from specialist alcohol and other drug
      treatment services, to identify the minimum level of clinical assessment
      information they would be willing to collect during a single treatment
      opportunity of 60-min in duration. The expert sample collectively identified 27
      assessment items, 7 of which subsequently met the Delphi consensus criteria. All
      participants considered the resulting model (7 items) to be clinically
      appropriate under normal circumstances; however, many stated they would be
      reluctant to strictly adhere to the model if it were implemented in practice.
      Participants suggested it would take them, on average, 40-min out of the 60-min
      intervention opportunity to collect the stated assessment information.

PMID- 19390959
TI  - Prevalence of the angiotensin I converting enzyme gene insertion/deletion
      polymorphism in a healthy Turkish population.
AB  - Angiotensin converting enzyme (ACE) plays an essential role in the renin
      angiotensin system. It converts angiotensin I to angiotensin II and inactivates
      bradykinin and tachykinins. Numerous studies have been published investigating
      associations of the ACE gene I/D polymorphism with various pathophysiological
      conditions. We examined the prevalence of the ACE I/D polymorphism in a sample of
      healthy volunteers from western Turkey, including 1063 healthy Turkish controls.
      Analysis of the ACE I/D gene polymorphisms by polymerase chain reaction found
      frequencies of 16.1% for the II genotype, 47.7% for the ID genotype, and 36.2%
      for the DD genotype. The allele frequency was 39.9% for the I alleles and 60.1%
      for the D allele. This study demonstrates that the allele and genotype frequency
      values for the Turkish population are similar to previously published frequencies
      for Caucasian populations.

PMID- 19390960
TI  - Molecular characterization of the pina gene in einkorn wheat.
AB  - Fifty-six sequences encoding the pina protein were characterized from three
      species or subspecies of einkorn wheat. These sequences contained 1,595
      nucleotides, including 1,270 conserved sites, 21 single nucleotide polymorphisms
      (SNPs), and 16 indels. The average frequency of SNPs and indels was one out of
      76.1 and 99.9 bases, respectively. Five SNPs and no indels were found in the
      translated sequences. Fourteen haplotypes were defined, and the accessions in
      each haplotype ranged from 1 to 18. There were nine haplotypes in Triticum
      monococcum ssp. aegilopoides, eight in T. monococcum ssp. monococcum, and two in
      T. urartu. Phylogenetic analysis showed that pina genes from different species or
      subspecies could be clearly differentiated based on the open reading frame. Genes
      from T. urartu grouped together, whereas genes from T. monococcum ssp.
      aegilopoides and T. monococcum ssp. monococcum were shared by three and two
      clusters, respectively. Both the haplotype and phylogenetic analyses indicated
      that T. monococcum ssp. aegilopoides was more diverse. These results would
      contribute to the understanding of functional aspects and efficient utilization
      of pina genes.

PMID- 19390961
TI  - Theorising interventions as events in systems.
AB  - Conventional thinking about preventive interventions focuses over simplistically
      on the "package" of activities and/or their educational messages. An alternative
      is to focus on the dynamic properties of the context into which the intervention
      is introduced. Schools, communities and worksites can be thought of as complex
      ecological systems. They can be theorised on three dimensions: (1) their
      constituent activity settings (e.g., clubs, festivals, assemblies, classrooms);
      (2) the social networks that connect the people and the settings; and (3) time.
      An intervention may then be seen as a critical event in the history of a system,
      leading to the evolution of new structures of interaction and new shared
      meanings. Interventions impact on evolving networks of person-time-place
      interaction, changing relationships, displacing existing activities and
      redistributing and transforming resources. This alternative view has significant
      implications for how interventions should be evaluated and how they could be made
      more effective. We explore this idea, drawing on social network analysis and
      complex systems theory.

PMID- 19390962
TI  - The fertility-related concerns, needs and preferences of younger women with
      breast cancer: a systematic review.
AB  - Breast cancer is the most commonly diagnosed type of cancer in reproductive aged
      women. Adjuvant systemic therapy is recommended in most women and has been
      demonstrated to reduce the risk of recurrence and increase survival. However,
      there may be a negative impact of adjuvant systemic therapy on fertility as well
      as on subsequent quality of life. There are a number of fertility preservation
      options currently available and relevant information regarding these options
      should be provided prior to commencing adjuvant treatment. The aim of the review
      is to identify the fertility-related needs, concerns and preferences of young
      women with early breast cancer. The databases MEDLINE and EMBASE were searched
      from 1988 onwards using keywords, and examining reference lists. Of the 499
      articles identified, 20 met eligibility criteria and were reviewed. Multiple
      fertility-related information needs specific to this group regarding menstrual
      changes and potential infertility attitudes to, and actual decisions made
      regarding, pregnancy breastfeeding and contraception emerged. Information on
      fertility-related decisions was rated as important, and the preferred methods for
      obtaining this information was consultation with a specialist or a decision aid
      early in the treatment plan. There is limited research about fertility-related
      needs, and even less on contraceptive preferences and the attitudes of health
      care providers towards fertility-related issues. No studies describing the
      development of tools to assist with decisions about fertility-related choices
      were identified. Young women with early breast cancer have specific fertility-
      and menopause-related needs and concerns, which are commonly not adequately
      addressed or discussed prior to commencing adjuvant therapy.

PMID- 19390963
TI  - Addressing intimacy and partner communication after breast cancer: a randomized
      controlled group intervention.
AB  - While quality of life for most breast cancer survivors (BCS) returns to normal by
      1 year post-treatment, problems in sexual function and intimacy often persist.
      The present study tested the efficacy of a 6-week psycho-educational group
      intervention in improving BCS's sexual well-being. We conducted a mailed survey
      of BCS 1-5 years post-diagnosis to identify a sample of women who reported
      moderately severe problems in body image, sexual function or partner
      communication, and were deemed eligible for the randomized intervention trial.
      Using a pre-randomized design, 70% (n = 284) were assigned to a 6-week psycho
      educational group intervention and 30% (n = 127) were assigned to a control
      condition (print material only); however, only 83 BCS agreed to participate in
      the intervention. Four months post-intervention, the intervention and control
      groups were not significantly different on the primary outcome of emotional
      functioning; however, BCS randomized to the intervention group were more likely
      to report improvements in relationship adjustment and communication as well as
      increased satisfaction with sex compared to controls. Members of the intervention
      group who were the least satisfied with their sexual relationship appeared to
      improve the most. Although modest in its effects, this intervention can be
      delivered in standard clinical settings. Having an identified treatment may help
      reduce physician reluctance to ask BCS about problems in intimacy and as
      appropriate, refer them for timely help.

PMID- 19390964
TI  - The TGFBR1*6A/9A polymorphism is not associated with differential risk of breast
      cancer.
AB  - A polymorphic 9-bp deletion in exon 1 of TGFBR1 (TGFBR1*6A) has been identified
      as a low-penetrance cancer susceptibility allele. The strongest association in
      the initial studies was with breast cancer; however, these studies included
      patients with different types of cancer, including colon, cervical and breast
      carcinomas, with only a small proportion being breast cancer patients. In
      subsequent case-control studies focussing on breast cancer alone, the results
      have been equivocal. In order to clarify whether TGFBR1*6A is associated with
      breast cancer risk, we have genotyped this polymorphism in 988 breast cancer
      cases and 1,016 controls from the West of Ireland and also performed a meta
      analysis of previously published data (5,150 cases and 6,344 controls). In our
      series from the West of Ireland, we found no association (genotypic odds ratio
      (OR) under a dominant model = 0.93, 95% confidence interval (CI) 0.73-1.19, P =
      0.57; allelic OR = 0.93, 95% CI 0.74-1.15, P = 0.49). Meta-analysis showed
      evidence of heterogeneity among studies. Using the random effects model, it was
      found that there was no evidence of an association of the *6A allele with breast
      cancer (genotypic OR under a dominant model = 1.10, 95% CI = 0.94-1.28, P = 0.24,
      allelic OR = 1.12, 95% CI 0.97-1.31, P = 0.13). In conclusion, our study shows
      that there is no association between TGFBR1*6A and breast cancer risk.

PMID- 19390965
TI  - Liver transplantation in the ethnic minority population: challenges and
      prospects.
AB  - In the USA, end-stage liver disease (ESLD) is a major cause of morbidity and
      mortality among ethnic minorities. Ethnic populations vary with respect to
      chronic liver disease prevalence, access to transplantation, and therapeutic
      outcomes post liver transplantation. These ethnic differences present unique
      challenges to healthcare professionals involved in the care of patients with
      chronic liver disease prior and post transplantation. This review will discuss
      the variations and challenges of liver transplantation in the ethnic minority
      population.

PMID- 19390966
TI  - Determinants of accelerated small intestinal transit in alcohol-related chronic
      pancreatitis.
AB  - Patients with chronic pancreatitis may have abnormal gastrointestinal transit,
      but the factors underlying these abnormalities are poorly understood.
      Gastrointestinal transit was assessed, in 40 male outpatients with alcohol
      related chronic pancreatitis and 18 controls, by scintigraphy after a liquid meal
      labeled with (99m)technetium-phytate. Blood and urinary glucose, fecal fat
      excretion, nutritional status, and cardiovascular autonomic function were
      determined in all patients. The influence of diabetes mellitus, malabsorption,
      malnutrition, and autonomic neuropathy on abnormal gastrointestinal transit was
      assessed by univariate analysis and Bayesian multiple regression analysis.
      Accelerated gastrointestinal transit was found in 11 patients who showed
      abnormally rapid arrival of the meal marker to the cecum. Univariate and Bayesian
      analysis showed that diabetes mellitus and autonomic neuropathy had significant
      influences on rapid transit, which was not associated with either malabsorption
      or malnutrition. In conclusion, rapid gastrointestinal transit in patients with
      alcohol-related chronic pancreatitis is related to diabetes mellitus and
      autonomic neuropathy.

PMID- 19390967
TI  - Eosinophilic esophagitis: perspectives of adult and pediatric
      gastroenterologists.
AB  - To survey pediatric (PGI) and adult gastroenterologists (AGI) regarding their
      perceptions about the etiology, diagnosis, and management of eosinophilic
      esophagitis (EoE), and to assess whether differences in the clinical approach to
      EoE exist between these subspecialists. A 21-item survey related to EoE was
      emailed to PGI who subscribe to the PEDSGI Bulletin Board, and to two AGI per
      Electoral College vote in the US, randomly selected from each state. The survey
      was voluntary, and consent was assumed based on survey submission. The responses
      were submitted anonymously and results compiled in a secure Web site. A total of
      249 physicians from across the globe responded to the survey, 68% of whom were
      PGI. The majority of respondents worked primarily in an academic institution or
      teaching hospital. Respondents revealed diagnosing an average of six cases
      (median 8, range 0-30) of EoE in the past 6 months. Ninety-two percent of AGI who
      see a patient with dysphagia and suspected EoE proceed to endoscopy with
      biopsies, compared to only 54% of PGI (P < 0.05); 38% of PGI would first perform
      an upper GI study. Both subspecialties agreed that biopsies of the proximal and
      distal esophagus are needed to make a definitive diagnosis of EoE. Fifty-eight
      percent PGI and 44% AGI defined EoE as an eosinophilic density of > or =20 per
      high power field (hpf) in esophageal biopsies. Seventy-seven percent of PGI but
      only 16% of AGI reported routine referral of patients for food allergy evaluation
      (P < 0.05). While 77% PGI and 91% of AGI would rely on a symptom-based follow-up,
      27% PGI versus 9% AGI follow patients with biopsies according to a pre-determined
      schedule and another 38% repeat biopsies as needed, versus 15% AGI. This survey
      exposes a few inconsistencies among gastroenterologists in the diagnosis,
      management, and follow-up of patients with EoE. The currently available practice
      guidelines for the diagnosis and management of EoE are largely based on
      retrospective studies and expert opinion. The results of this survey suggest that
      a collaborative effort based on robust research is required upon us to develop
      evidence for how we care for these patients.

PMID- 19390968
TI  - Laparotomy attenuates lipopolysaccharide-induced gastric bleeding in the rat.
AB  - Lipopolysaccharide (LPS) increases systemic inflammation and causes
      duodenogastric reflux of bile and gastric bleeding. Laparotomy prevents gastric
      injury from the luminal irritant bile, but its effects on LPS-induced gastric
      injury are unknown. We hypothesized that laparotomy would diminish inflammation
      and attenuate gastric bleeding caused by LPS. In the rat, laparotomy, done either
      before or after administration of LPS, attenuated LPS-induced bile reflux,
      gastric bleeding, and cyclooxygenase-2, but not inducible nitric oxide synthase,
      expression when compared to controls given LPS. Laparotomy also blunted LPS
      induced changes in serum cytokine production. These data suggest that laparotomy
      has gastroprotective effects by preventing LPS-induced bile reflux and gastric
      bleeding and by a mechanism mediated, at least in part by cyclooxygenase-2.

PMID- 19390969
TI  - Association of tumor necrosis factor-alpha gene promoter polymorphisms with acute
      viral hepatitis in the Indian population.
AB  - The key elements that determine the host response to either the self-limited or a
      severe fulminant form of liver disease are unclear. We have investigated the
      potential association of single nucleotide polymorphisms (SNPs) in the promoter
      region of tumor necrosis factor-alpha (TNFalpha) in their susceptibility to acute
      viral hepatitis (AVH) and fulminant hepatic failure (FHF) patients exhibiting
      specific viral etiology. A total of 124 individuals including 64 cases comprising
      27 FHF, 37 AVH, and 60 healthy controls were recruited. SNPs at -238 (G/A), -308
      (G/A), -857 (C/T), and -863 (C/A) of TNFalpha were detected by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by
      direct sequencing. Serum levels of TNFalpha were determined at admission and
      death or recovery. Association between the TNFalpha genotype and susceptibility
      to FHF was not evident; however, carrier genotypes in relation to the -308
      (GA/AA) and -857 (CT/TT) loci were found to be significantly (P < or = 0.05)
      associated with susceptibility to AVH in relation to controls. The mean TNFalpha
      serum levels at admission were significantly higher (P < 0.001) in FHF than AVH
      patients, but no marked difference was observed between FHF-E (expired; n = 17)
      and FHF-S (survivors; n = 10), though the former were comparatively higher. This
      study suggests that SNPs at -308 and -857 of the TNFalpha promoter may represent
      an increased risk for the development of AVH but not for FHF in the Indian
      population.

PMID- 19390970
TI  - Halofuginone, a specific inhibitor of collagen type 1 synthesis, ameliorates
      oxidant colonic damage in rats with experimental colitis.
AB  - To evaluate the effect of halofuginone on trinitrobenzene sulfonic acid (TNBS)
      induced colonic injury, rats were given halofuginone (40 microg/kg,
      intraperitoneally) or saline 1 h before the induction of colitis, and the
      injections were continued twice daily for 3 days until they were decapitated.
      High macroscopic and microscopic damage scores, elevated colonic wet weights,
      colonic myeloperoxidase activity, malondialdehyde and tissue collagen level, and
      luminol chemiluminescence values, and marked reduction in glutathione level of
      the saline-treated colitis group were all reversed by treatment with
      halofuginone. In conclusion, halofuginone exerts beneficial effects in TNBS
      induced colonic inflammation in rats. The anti-inflammatory effects of
      halofuginone appear to involve suppression of neutrophil accumulation,
      preservation of endogenous glutathione, and inhibition of reactive oxidant
      generation. Halofuginone also shows antifibrotic effect via inhibition of tissue
      collagen production. The present data encourage possible use of the antifibrotic
      halofuginone as an anti-inflammatory agent in improving oxidative injury in
      colitis.

PMID- 19390971
TI  - An adaptive approach to family-centered intervention in schools: linking
      intervention engagement to academic outcomes in middle and high school.
AB  - This study examined the impact of an adaptive approach to family intervention in
      public schools on academic outcomes from age 11 to 17. Students were randomly
      assigned to the three-session Family Check-Up (FCU), which is designed to
      motivate change in parenting practices by using an assessment-driven approach and
      strengths-based feedback. All services were voluntary, and approximately 25% of
      the families engaged in the FCU. Compared with matched controls, adolescents
      whose parents received the FCU maintained a satisfactory GPA into high school,
      and intervention engagement was associated with improved attendance. The highest
      risk families were the most likely to engage in the family-centered intervention,
      suggesting the efficacy of integrating supportive services to families in the
      context of other schoolwide approaches to promote the success and achievement of
      vulnerable students.

PMID- 19390972
TI  - Self care and health-seeking behavior of migrant farmworkers.
AB  - There are an estimated three million migrant and seasonal farmworkers (MSFW) in
      the United States. In addition to the inherent dangers of farm work, numerous
      factors place MSFW at even greater risk for work-related injuries. Little is
      known about how MSFW care for work-related injuries, and how the decision to seek
      professional care is made. A prospective survey using face-to-face structured
      interviews was used to explore the type and frequency of occupational injuries as
      well as self-care and health-care seeking practices of MSFW. Musculoskeletal
      injuries were the most commonly reported injuries, followed by injuries of the
      skin and chemical exposure. Self care with over-the-counter remedies was the
      predominant method of dealing with injuries, and, with the exception of chemical
      exposure, was found to be for the most part, appropriate. The reported use of
      alternative medicine or herbal remedies was low. Future research efforts should
      focus on ergonomic modifications and farmworker education to reduce or prevent
      musculoskeletal injuries. The number of reported chemical exposures and
      inappropriate treatment draw attention to the need for continued efforts for both
      primary prevention of exposure and optimal treatment once exposure occurs.

PMID- 19390973
TI  - Post-involvement difficulties experienced by former members of charismatic
      groups.
AB  - Limited qualitative studies have been conducted with former members of
      charismatic groups, especially in Australia. The majority of studies with former
      members have been conducted by psychologists through quantitative methodologies
      and clinical case studies. Qualitative studies that explore the phenomenon of
      charismatic group involvement have predominantly been carried out by
      sociologists, and these focus on current members of such groups. Sociologists and
      psychologists have drawn seemingly contradictory conclusions from their study.
      This study aims to narrow the gap by investigating adjustment to life after
      involvement with a charismatic group as experienced by former members of such
      groups through the use of qualitative methods. Seven participants from four
      different groups were recruited via purposive sampling and modified snowball
      sampling. A qualitative methodology informed by phenomenology was chosen. In
      depth interviews were used to explore the participants' accounts of adjusting to
      life after involvement. The findings of this study suggest that the experiences
      of former members of charismatic groups may be comparable to others who have
      experienced extreme transitions and adjustments or relationships where
      significant power differentials exist.

PMID- 19390974
TI  - Effects of 5 years of growth hormone (GH) replacement therapy on cardiac
      parameters and physical performance in adults with GH deficiency.
AB  - The purpose of this study was to evaluate the effects of 5 years of GH
      substitution on cardiac structure and function, physical work capacity and blood
      pressure levels in adults with GH deficiency (GHD). Fourteen patients were
      clinically assessed every 3 months for 5 years. Transthoracic echocardiography
      and exercise test were performed at baseline, 24, 48 and 60 months. Blood
      pressure (BP) was measured by means of ambulatory monitoring of blood pressure at
      baseline, 6, 12, 24 and 60 months. Left ventricular mass and its index increased
      progressively during the 5 years of GH substitution (P = 0.008 and 0.007,
      respectively). There were no significant changes in all others cardiac parameters
      evaluated. It was observed a significant improve in functional capacity (P <
      0.001) and maximal oxygen uptake (P = 0.006) during the treatment. Diurnal
      systolic BP increased by 15 mmHg (P = 0.024) and diurnal diastolic BP by 4.5 mmHg
      (P = 0.037). There was no change in dirnal systolic pressure load but a
      considerable but non-statistically significant reduction in diurnal diastolic
      pressure load was observed during the study. During the night diastolic BP
      increased by 4 mmHg (P = 0.012) despite a substantial but non-statistically
      significant reduction in diastolic pressure load. We observed an increase in the
      proportion of persons with a non-physiological nocturnal fall (non-dippers)
      throughout the study (from 36.4% at baseline to 54.6% after 60 months of
      therapy). We concluded that 5 years of GH replacement promoted positive effects
      on exercise capacity and maximum oxygen uptake in spite of a modest increase in
      BP levels and left ventricular mass. Continuous monitoring is mandatory to arrive
      at further conclusions concerning the effects of GH substitution in adults on
      cardiovascular parameters with respect to possible unfavorable long term effects.

PMID- 19390975
TI  - Comparative effectiveness research: making it work for those we serve.

PMID- 19390976
TI  - Difference in the lubrication efficiency of bovine and vegetable-derived
      magnesium stearate during tabletting.
AB  - The purpose of this work was to evaluate and compare the functionality of bovine
      fatty acids-derived (MgSt-B) and vegetable fatty acids-derived (MgSt-V) magnesium
      stearate powders when used for the lubrication of granules prepared by high-shear
      (HSG) and fluid bed (FBG) wet granulation methods. The work included evaluation
      of tablet compression and ejection forces during tabletting and dissolution
      testing of the compressed tablets. Granules prepared by both granulation methods
      required significantly lower ejection force (p < 0.01) when lubricated with the
      MgSt-V powder as compared to those lubricated with the MgSt-B powder. Granules
      prepared by the HSG method and lubricated with the MgSt-V powder also required
      significantly lower compression force (p < 0.01) to produce tablets of similar
      weight and hardness as compared to those lubricated with the MgSt-B powder. The
      dissolution profiles were not affected by these differences and were the same for
      tablets prepared by same granulation method and lubricated with either magnesium
      stearate powder. The results indicate significant differences (p < 0.01) between
      lubrication efficiency of the MgSt-B and the MgSt-V powders and emphasize the
      importance of functionality testing of the MgSt powders to understand the impact
      of these differences.

PMID- 19390977
TI  - Evaluation of protective efficacy of Spirulina platensis against collagen-induced
      arthritis in rats.
AB  - AIM: To assess the protective efficacy of Spirulina platensis against collagen
      induced arthritis (CIA) in female Wistar rats based on the changes in paws
      thickness, serum albumin, cholesterol, lipid peroxidation, alkaline phosphatase
      and acid phosphatase activities and histology of paw joints. METHODS: Arthritis
      was induced by intradermal injection of Collagen and Freund's adjuvant incomplete
      suspension at several sites on the back with a dose of 2 mg kg(-1) of body weight
      and boosted with 0.1 ml intradermally at the base of the tail. CIA rats were
      orally treated with 200 and 400 mg kg(-1) per oral of S. platensis from 0 to 45th
      day. RESULTS: S. platensis at 400 mg kg(-1) per oral significantly elevates serum
      albumin and decreases the serum cholesterol, alkaline phosphatase and acid
      phosphatase activities, lipid peroxidation, paw thickness as well as normalize
      the joint histopathology of CIA rats. CONCLUSIONS: S. platensis (400 mg kg(-1))
      significantly normalizes changes observed in arthritic rats to near normal
      conditions, indicates that S. platensis has promising protective efficacy against
      CIA rats.

PMID- 19390978
TI  - On the function of cornuti, sclerotized structures of the endophallus of
      Lepidoptera.
AB  - The genitalia of many male insects include structures whose functions are unknown
      or poorly understood. The endophallus of many Lepidoptera bears sclerotized
      structures known as cornuti, which in some species break off during copulation
      and remain within the female genital tract ("deciduous" cornuti). I describe
      previous and original hypotheses on the role of cornuti, identify the selective
      pressures invoked by these hypotheses, propose different ways of testing them and
      briefly review pertinent evidence. I describe ten functional hypotheses for non
      deciduous cornuti and four for deciduous cornuti; six hypotheses invoke natural
      selection and eight involve sexual selection. In some cases more than one of the
      proposed functions could be performed by cornuti; evolutionary change from one
      function to another is also possible. I suggest that the wide morphological
      variation observed in non-deciduous cornuti across taxa supports hypotheses
      invoking sexual selection. I propose that the function and evolution of cornuti
      can be revealed with a combination of descriptive studies, cornuti removal
      experiments and comparative tests.

PMID- 19390980
TI  - Assessment of elemental concentrations in the urban air (case study: Tehran
      city).
AB  - Tehran is one of the megacities of the world with a population of over eight
      million. Its air is highly polluted mainly due to the suspended particulate
      matters, which encompasses a wide spectrum of chemical elements. These elements
      based on their type, size, and impact on the life cycle have various
      environmental and heath risks. In this research, the neutron activation method is
      used to determine the concentration levels of Al, Ba, Fe, Mg, and V in the urban
      air. Thus, two districts of Tehran with different characteristics are selected.
      District 21 includes much of the industries located in Tehran metropolitan and is
      considered as an industrial area. In contrast, district 22 lacks any significant
      industrial activity. It is a newly established and expanding district adjacent to
      district 21 with a great deal of constructional activities. For the measurement
      of the suspended particulate matters in the air, the various sections of the
      aforesaid districts with industrial, residential, heavily congested traffic,
      residential/commercial, residential/heavily congested traffic, and
      residential/industrial classifications were identified. Subsequently, 24 sampling
      stations were selected. The sampling of the suspended particulate matters was
      conducted with the aid of a high volume pump containing 125 mm cellulose filters
      in two different time intervals. After completion of the sampling process, the
      samples were prepared and sent to the research reactor of the Iran Nuclear Energy
      Organization for Neutron Activation. During the next steps, the radiations
      emitted from the samples were registered, the radiation curves were plotted, and
      the amounts of the trace elements were determined. As a result, the average
      concentration levels of Al, Ba, Fe, Mg, and V were identified to be 3.301140,
      2.273658 x 10, 4.0681696 x 10(-1), 3.5525475 x 10(-1), and 3.04075 x 10(-2)
      microg/m(3), respectively. Moreover, the emission sources of the aforesaid
      elements into the air were identified. The concentration levels of these elements
      in the industrial and heavily congested traffic sections were higher. Finally, it
      was concluded that the statistical analysis of these elements presents a
      meaningful correlation among them.

PMID- 19390979
TI  - Differential effect of halothane on motor evoked potentials elicited by
      transcranial electric or magnetic stimulation in the monkey.
AB  - OBJECTIVE: Halothane (HAL) is known to depress motor evoked potentials produced
      by transcranial magnetic (tcMMEP) or transcranial electric (tcEMEP) stimulation.
      This study was designed to determine if differences existed between tcEMEP and
      tcMMEP with increasing HAL concentra- tions. METHODS: tcMMEP and tcEMEP were
      characterized during 0-2% inspired HAL in 10 adult cynomologous monkeys during a
      baseline anesthesia with a continuous ketamine infusion. tcEMEP and tcMMEP were
      assessed by measuring the onset latency (time from stimulation to the initial
      response), amplitude of the thenar compound action potential response and
      threshold (relative power required to elicit a response). Cortical stimulation
      was accomplished using a Cadwell MES-10 (tcMMEP) and Digitimer Dl80 (tcEMEP).
      RESULTS: The baseline (no HAL) onset latency for tcEMEP (10.68 ms) was
      significantly shorter than that of tcMMEP (12.28 ms) (P < 0.05). The amplitudes
      (7,916, 4,858 microV, respectively) were not significantly different (P > 0.112).
      The onset latency increased and amplitude decreased for both techniques (no
      significant difference between tcEMEP and tcMMEP) with increase in HAL. All
      animals lost their responses below 2% HAL. In each animal the tcMMEP was lost at
      a HAL concentration below or equal to that for tcEMEP. T The ED(50) (where 50% of
      the animals lost the response) was significantly different between tcMMEP (0.66%
      HAL) and tcEMEP (1.04% HAL) (P < 0.05). The relative threshold gradually
      increased for tcEMEP and abruptly increased above 0.4% HAL for tcMMEP.
      CONCLUSIONS: These differences in sensitivity to HAL are consistent with other
      studies with intravenous anesthesia and are consistent with the known difference
      in the physiological mechanisms by which magnetic and electrical stimulation
      activates the motor cortex.

PMID- 19390981
TI  - Survey of Sarcocystis infection in slaughtered cattle in Kerman, Iran.
AB  - The parasite of genus Sarcocystis is one of the most commonly found parasite in
      domestic animals worldwide. Some species of Sarcocystis cause important economic
      loss when causing clinical and sub clinical disease. The aim of this study was to
      determine the prevalence of Sarcocystis in slaughtered Cattle in Kerman, Iran.
      The prevalence of Sarcocystis spp. infection was investigated in 480 cattle,
      slaughtered from May 2005 to February 2006 in the Kerman, Iran using naked eye
      examination for macroscopic Sarcocysts, and peptic digestion, muscle squash,
      squeezing methods for microscopic types. Muscles from heart, tongue, and
      esophagus, cervical and abdominal muscles of 480 slaughtered cattle were examined
      for Sarcocystis cysts. The prevalence of microscopic Sarcocystis cysts in cattle
      was detected in 100% and there was no macroscopic cyst in examined cattle.

PMID- 19390982
TI  - Huizache (Acacia farnesiana) whole pods (flesh and seeds) as an alternative feed
      for sheep in Mexico.
AB  - Two experiments were undertaken to evaluate the use of pods from Huizache (Acacia
      farnesiana), common in the arid and semiarid regions of Mexico, on the
      perfromance and apparent digestibility in Pelibuey Mexican hair growing ewe
      lambs. Twenty-four Pelibuey ewe lambs were used in the animal performance
      experiment, with a mean live weight of 14.91 +/- 1.48 kg, randomnly allocated to
      three groups which received ad libitum for 77 days (11 weeks) experimental whole
      rations T0 with 0%, T12 with 12% or T24 with 24% inclusion of dried and ground
      Huizache pods. Dry matter intakes (g/kg (0.75) daily) were 83, 95, 90 for T0,
      T12, and T24 respectively (P > 0.05). Mean daily live-weight gain was 90, 75, and
      63 g/day for T0, T12, and T24 (P < 0.001). Nine Pelibuey ewe lambs were used to
      determine apparent digestibility in vivo of the experimental diets using a 3 x 3
      latin square design repeated three times. There were differences in the
      digestibility of dry matter (P < 0.001), organic matter (P < 0.001), nitrogen (P
      < 0.031), neutral detergent fibre (P < 0.002), and acid detergent fibre (P <
      0.001) being lower in T24. Huizache pods may be an alternative feed when included
      up to 12% of dry matter in the diets for sheep growing moderately.

PMID- 19390983
TI  - Search for Salmonella spp. in ostrich productive chain of Brazilian southeast
      region.
AB  - We analyzed ostriches from an equipped farm located in the Brazilian southeast
      region for the presence of Salmonella spp. This bacterium was investigated in 80
      samples of ostrich droppings, 90 eggs, 30 samples of feed and 30 samples of
      droppings from rodents. Additionally, at slaughter-house this bacterium was
      investigated in droppings, caecal content, spleen, liver and carcasses from 90
      slaughtered ostriches from the studied farm. Also, blood serum of those animals
      were harvested and submitted to serum plate agglutination using commercial
      Salmonella Pullorum antigen. No Salmonella spp. was detected in any eggs, caecal
      content, liver, spleen, carcass and droppings from ostriches and rodents.
      However, Salmonella Javiana and Salmonella enterica subsp. enterica 4, 12: i:-
      were isolated from some samples of feed. The serologic test was negative for all
      samples. Good sanitary farming management and the application of HACCP principles
      and GMP during the slaughtering process could explain the absence of Salmonella
      spp. in the tested samples.

PMID- 19390984
TI  - Effects on performance of growing pigs fed diets containing different levels of
      dried cashew pulp.
AB  - The purpose was to investigate the use of dried cashew pulp (DrCP), the sun-dried
      residue after juice has been extracted from the cashew apple, as a feed
      ingredient in growing pig diets. The growth rate, feed intake, feed to gain ratio
      and cost of gain of grower pigs fed diets containing 0 (0DrCP), 100 (100DrCP),
      150 (150DrCP) or 200 (200DrCP) g kg(-1) of dried cashew pulp was investigated in
      a feeding trial set up as a Completely randomized design with 4 treatments
      replicated 3 times and lasting 112 days. There were no significant differences (P
      > 0.05) among treatments in the parameters measured. It was concluded that dried
      cashew pulp could be used in growing pig diets up to a level of 200 g kg(-1)
      without any deleterious effects. Future work will look at higher levels of DrCP
      inclusion in the diets of growing pigs.

PMID- 19390985
TI  - New mobile genetic elements in Cupriavidus metallidurans CH34, their possible
      roles and occurrence in other bacteria.
AB  - Cupriavidus metallidurans strain CH34 is a beta-Proteobacterium that thrives in
      low concentrations of heavy metals. The genetic determinants of resistance to
      heavy metals are located on its two chromosomes, and are particularly abundant in
      the two megaplasmids, pMOL28 and pMOL30. We explored the involvement of mobile
      genetic elements in acquiring these and others traits that might be advantageous
      in this strain using genome comparison of Cupriavidus/Ralstonia strains and
      related beta-Proteobacteria. At least eleven genomic islands were identified on
      the main replicon, three on pMOL28 and two on pMOL30. Multiple islands contained
      genes for heavy metal resistance or other genetic determinants putatively
      responding to harsh environmental conditions. However, cryptic elements also were
      noted. New mobile genetic elements (or variations of known ones) were identified
      through synteny analysis, allowing the detection of mobile genetic elements
      outside the bias of a selectable marker. Tn4371-like conjugative transposons
      involved in chemolithotrophy and degradation of aromatic compounds were
      identified in strain CH34, while similar elements involved in heavy metal
      resistance were found in Delftia acidovorans SPH-1 and Bordetella petrii
      DSM12804. We defined new transposons, viz., Tn6048 putatively involved in the
      response to heavy metals and Tn6050 carrying accessory genes not classically
      associated with transposons. Syntenic analysis also revealed new transposons
      carrying metal response genes in Burkholderia xenovorans LB400, and other
      bacteria. Finally, other putative mobile elements, which were previously
      unnoticed but apparently common in several bacteria, were also revealed. This was
      the case for triads of tyrosine-based site-specific recombinases and for an int
      gene paired with a putative repressor and associated with chromate resistance.

PMID- 19390986
TI  - Marinobacter zhanjiangensis sp. nov., a marine bacterium isolated from sea water
      of a tidal flat of the South China Sea.
AB  - A novel Gram-negative, catalase- and oxidase-positive, non-sporulating, rod
      shaped, aerobic bacterium, designated strain JSM 078120(T), was isolated from sea
      water collected from a tidal flat of Naozhou Island, South China Sea. Growth
      occurred with 1-15% (w/v) total salts (optimum, 2-4%), at pH 6.0-10.0 (optimum,
      pH 7.5) and at 4-35 degrees C (optimum, 25-30 degrees C). The major cellular
      fatty acids were C(18:1) omega9c, C(16:0), C(12:0) 3-OH and C(16:1) omega7c. The
      predominant respiratory quinone was ubiquinone Q-9, and the genomic DNA G + C
      content was 60.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that strain JSM 078120(T) should be assigned to the genus Marinobacter,
      being related most closely to the type strains of Marinobacter segnicrescens
      (sequence similarity 98.2%), Marinobacter bryozoorum (97.9%) and Marinobacter
      gudaonensis (97.6%). The sequence similarities between the novel isolate and the
      type strains of other recognized Marinobacter species ranged from 96.7 (with
      Marinobacter salsuginis) to 93.3% (with Marinobacter litoralis). The levels of
      DNA-DNA relatedness between strain JSM 078120(T) and the type strains of M.
      segnicrescens, M. bryozoorum and M. gudaonensis were 25.3, 20.6 and 18.8%,
      respectively. The combination of phylogenetic analysis, DNA-DNA relatedness,
      phenotypic characteristics and chemotaxonomic data supported the view that strain
      JSM 078120(T) represents a novel species of the genus Marinobacter, for which the
      name Marinobacter zhanjiangensis sp. nov. is proposed. The type strain is JSM
      078120(T) (= CCTCC AB 208029(T) = DSM 21077(T) = KCTC 22280(T)).

PMID- 19390987
TI  - Bacterial growth properties at low optical densities.
AB  - A method for accurate quantification of growth rate and yield of bacterial
      populations at low densities was developed with a modified version of a stepwise
      linear model for fitting growth curves based on optical density measurements, and
      adapted to measurements at low optical densities in 96-well microtiter plates.
      The method can be used for rapid and precise estimates of growth rate and yield,
      based on optical density measurements of large numbers of cultures of Escherichia
      coli. E. coli B lines were serially propagated at low glucose concentration
      during a long-term evolution experiment. Growth rate and yield of populations
      sampled from each of 12 lines that evolved for 20,000 generations under these
      conditions and two ancestral clones was measured. Populations were grown at three
      different glucose concentrations. Consistent with earlier findings, statistical
      analysis showed that both exponential growth rate and yield per unit of glucose
      differed significantly between the three glucose concentrations tested.
      Significant adaptation of the evolved populations to the nutrient conditions in
      which they evolved for 20,000 generations was observed.

PMID- 19390988
TI  - Alteromonas halophila sp. nov., a new moderately halophilic bacterium isolated
      from a sea anemone.
AB  - A pale yellow-colored, moderately halophilic, Gram-negative, catalase- and
      oxidase-positive, non-sporulating, rod-shaped, motile, aerobic bacterium,
      designated strain JSM 073008(T), was isolated from a sea anemone (Anthopleura
      xanthogrammica) collected from Naozhou Island, Leizhou Bay, South China Sea. The
      organism was able to grow with 1-20% (w/v) total salts (optimum, 5-10%), at pH
      6.0-10.0 (optimum, pH 7.5) and 10-40 degrees C (optimum, 25-30 degrees C). The
      major cellular fatty acids were C(16:0), C(16:1) omega7c/iso-C(15:0) 2-OH and
      C(18:1) omega7c. The polar lipids consisted of phosphatidylethanolamine,
      phosphatidylglycerol and an unidentified phospholipid. The predominant
      respiratory quinone was Q-8 and the genomic DNA G + C content was 47.5 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain JSM
      073008(T) should be assigned to the genus Alteromonas, being most closely related
      to Alteromonas hispanica F-32(T) (sequence similarity 96.9%), followed by
      Alteromonas genovensis LMG 24078(T) (96.6%) and Alteromonas litorea TF-22(T)
      (96.4%). The sequence similarities between the novel isolate and the type strains
      of other recognized Alteromonas species ranged from 95.9% (with Alteromonas
      stellipolaris ANT 69a(T)) to 94.5% (with Alteromonas simiduii BCRC 17572(T)). The
      combination of phylogenetic analysis, phenotypic characteristics and
      chemotaxonomic data supported the view that strain JSM 073008(T) represents a new
      species of the genus Alteromonas, for which the name Alteromonas halophila sp.
      nov. is proposed. The type strain is JSM 073008(T) (=CCTCC AA 207035(T) = KCTC
      22164(T)).

PMID- 19390989
TI  - Comparative tolerances of various Beauveria bassiana isolates to UV-B irradiation
      with a description of a modeling method to assess lethal dose.
AB  - The tolerances of 20 Beauveria bassiana isolates derived from host insects
      worldwide to UV-B irradiation were assessed quantitatively in multi-dose
      bioassays. Conidial suspensions of the isolates smeared on glass slides were
      exposed to the gradient UV-B doses of 0.1-1.6 J cm(-2) (D), which generated from
      0.75 to 10.17 min irradiation of weighted 312-nm wavelength at 2.0-2.61 mW cm(
      2). Irradiated conidia were then incubated for 24 h at 25 degrees C under
      saturated humidity. The ratio of germination at each dose over that in the blank
      control was defined as survival index (I (s)). For all isolates, the I (s) - D
      observations fit well with the survival model I (s) = 1/[1 + exp(a + bD)] (0.94 <
      or = r (2) < or = 0.99) generated widely spanned lethal doses of 0.154-0.928,
      0.240-1.139, and 0.383-1.493 J cm(-2) for their losses of 50%, 75%, and 95%
      viabilities, respectively. These were far below the solar UV-B dose of 2.439 J
      cm(-2) measured in a sunny day during the summer. The large variation of UV-B
      tolerance among the isolates indicates a necessity to select UV-tolerant
      candidates for formulations applied to insect control during summer. The highly
      efficient bioassay method was developed to measure accurately the UV-B tolerances
      of fungal biocontrol agents as lethal doses.

PMID- 19390991
TI  - Cell type-specific regulation of CCN2 protein expression by PI3K-AKT-FoxO
      signaling.
AB  - The biological activity of connective tissue growth factor (CTGF, CCN2) is
      regulated at the level of intracellular signaling leading to gene expression, and
      by its extracellular interaction partners which determine the functional outcome
      of CCN2 action. In this overview, we summarize the data which provide evidence
      that one of the major signaling pathways, phosphatidylinositol-3 kinase (PI3K)
      AKT signaling, shows a remarkable cell type-dependence in terms of regulation of
      CCN2 expression. In smooth muscle cells, fibroblasts, and epithelial cells,
      inhibition of this pathway either reduced CCN2 expression or was not involved in
      CCN2 gene expression depending on the stimulus used. In microvascular endothelial
      cells by contrast, activation of PI3K-AKT signaling was inversely related to CCN2
      expression. Upregulation of CCN2 upon inhibition of PI3K-AKT was also observed in
      primary cultures of human endothelial cells (HUVEC) exposed to laminar flow in an
      in vitro flow-through system. In different types of endothelial cells, FoxO
      transcription factors, which are negatively regulated by AKT, were identified as
      potent activators of CCN2 gene expression. In HUVEC, we observed a correlation
      between enhanced nuclear localization of FoxO1 and increased synthesis of CCN2
      protein in areas of non-uniform shear stress. These data indicate that FoxO
      proteins are key regulators of CCN2 gene expression which determine the effect of
      PI3K-AKT activation in terms of CCN2 regulation. Short summary
      Phosphatidylinositol-3 kinase (PI3K)-AKT signaling shows a remarkable cell type
      dependence in terms of regulation of CCN2 expression. In endothelial cells
      activation of PI3K - AKT signaling was inversely related to CCN2 expression. FoxO
      transcription factors, which are negatively regulated by AKT, were identified as
      potent activators of CCN2 gene expression.

PMID- 19390990
TI  - Primary care providers' willingness to recommend BRCA1/2 testing to adolescents.
AB  - Clinical practice guidelines discourage pediatric genetic testing for BRCA1/2
      mutations due to a lack of timely medical benefit and psychosocial risk. Yet,
      some high risk families approach primary care providers (PCPs) about testing
      adolescents, and little is known about PCPs attitudes regarding these requests.
      We assessed recommendations for testing to a composite patient (a healthy 13-year
      old female, mother is a BRCA mutation carrier) among 161 adolescent and family
      PCPs attending a national medical conference. Testing recommendations were
      measured with a multidimensional scale that assessed perspectives on informed
      consent, genetic counseling, and insurance coverage. PCPs expressed moderate
      willingness to recommend testing; surprisingly, 31% recommended adolescent
      testing "unconditionally." In multivariable regression modeling, recommendation
      was positively associated with higher clinical practice volume (P < .05) and
      greater frequency of ordering other pediatric genetic tests (P < .01). Despite a
      decade of clinical practice guideline advice to the contrary, experienced PCPs
      may still be inclined to recommend BRCA1/2 genetic testing to adolescents from
      high risk families. When paired with emerging data on the relative safety and
      efficacy of breast cancer genetic testing for high risk women and the advent of
      direct-to-consumer marketing of BRCA1/2 cancer genetic tests, professional
      societies may need to explore best practices to counsel high risk families and
      their PCPs about the potential risks and benefits of pediatric BRCA1/2 testing.

PMID- 19390992
TI  - Adult extrarenal Wilms' tumor mimicking mixed epithelial and stromal tumor in the
      retroperitoneum: a case report with immunohistochemical study and review of the
      literature.
AB  - We report an extremely rare case of adult extrarenal Wilms' tumor (WT) in a 52
      year-old woman who presented with fever and abdominal distension. Computed
      tomography revealed a well-defined mass lesion measuring 15.0 cm in the right
      retroperitoneum and that was in contact with the right kidney. The mass and
      kidney were surgically removed. Grossly, the mass was well-defined, measuring
      16.3 x 11.0 x 9.8 cm, and appearing grayish-white in color. The border between
      the mass and the kidney was well-defined. Histologically, the tumor showed a
      triphasic pattern consisting of stromal, epithelial and blastemal components. The
      stromal component was predominant in the tumor and consisted both of spindle
      cells and smooth muscle cells. The epithelial component showed a mature glandular
      structure. Immunohistochemically, the stromal component was positive for
      vimentin, smooth muscle actin and desmin. The blastemal component was positive
      for vimentin, while the epithelial component was positive for cytokeratin (CK)
      18, CK7 and vimentin. WT-1 was negative in the all three components, and the Ki
      67 proliferation index was low. The postoperative histopathological diagnosis
      indicated extrarenal WT arising in the retroperitoneum. Although not treated by
      either chemotherapy or radiation therapy, she was free from disease recurrence
      for 30 months after surgery. To the best of our knowledge, this report is only
      the fourth case of adult extrarenal WT arising in the retroperitoneum.
      Furthermore, the present case showed predominant smooth muscle differentiation
      and a mature glandular structure, mimicking a mixed epithelial and stromal tumor.

PMID- 19390993
TI  - False positive CT angiography in brain death.
AB  - INTRODUCTION: Ancillary testing is frequently required in the determination of
      death by brain criteria, particularly in cases in which the clinical examination
      is drawn into question. Newer tests, such as computed tomographic angiography
      (CTA), have garnered enthusiasm for their ease of performance, but have not been
      validated as acceptable tests compared with a gold standard. CASE: We present a
      case of a 31-year-old patient who was felt to have cerebral circulatory arrest on
      CTA, but was subsequently found to have evidence of preserved cerebral blood flow
      on transcranial Doppler, thus precluding the diagnosis death by brain criteria.
      DISCUSSION: CTA is not a validated confirmatory test for cerebral circulatory
      arrest in brain death, and may be falsely positive. CONCLUSION: CTA should be
      studied further in comparison to validated tests, such as conventional
      angiography or single photon emission computed tomography (SPECT), before being
      accepted as a standard ancillary test in determining death by brain criteria.

PMID- 19390994
TI  - The AHA Guidelines for the Management of SAH: what we know and so much we need to
      learn.

PMID- 19390995
TI  - Small cell lung cancer: significance of RB alterations and TTF-1 expression in
      its carcinogenesis, phenotype, and biology.
AB  - Small cell lung cancer (SCLC) exhibits highly aggressive behavior and has a poor
      prognosis. While numerous investigations have been carried out, the exact
      mechanism of its carcinogenesis and aggressiveness is still unclear. SCLC is
      categorized as a neuroendocrine neoplasia and has a genetic profile characterized
      by universal alterations of the RB and TP53 genes. Epidemiological studies
      indicate the majority of SCLCs to be caused by smoking and the TP53 mutational
      pattern to be consistent with that evoked by smoke carcinogens; however, there is
      no direct evidence that such carcinogens induce alterations to RB in SCLC. While
      the importance of these alterations in the carcinogenesis of SCLC is strongly
      suggested, the exact molecular mechanism has been only little elucidated. SCLC
      cells almost always express mammalian achaete-scute homolog-1 (MASH1) and thyroid
      transcription factor-1 (TTF-1). MASH1 plays a critical role in neuroendocrine
      differentiation. TTF-1 is a characteristic marker of distal airway cells and
      pulmonary adenocarcinomas, but is also expressed in extrapulmonary neuroendocrine
      cancers. Thus, TTF-1 may well play a significant role in the development of
      neuroendocrine cancers. Recent studies indicate that the airway stem cell is
      committed to the neuroendocrine lineage through MASH1 and Notch signaling and
      that only RB-deleted neuroendocrine cells selectively proliferate in response to
      E2F3, eventually undergoing transformation to neuroendocrine cancer cells,
      probably in concert with TP53 gene aberrations. Thus, alterations of both the RB
      and TP53 genes are central to the carcinogenesis of SCLC, while many other
      factors including MASH1 and TTF-1 contribute to the development and biological
      behavior of SCLC.

PMID- 19390996
TI  - Hypothyroid Graves' disease complicated with elephantiasis nostras verrucosa
      (ENV): a case report and review of the literature.
AB  - Thyroid dermopathy is not a frequent feature of hyperthyroid Graves' disease,
      being present in less than 5% of the patients. Graves' disease has been shown to
      exist in euthyroid or hypothyroid forms in untreated patients. Here, we describe
      a case of hypothyroid Graves' disease with elephantiasis nostras verrucosa (ENV),
      which is an extreme form of thyroid dermopathy (TD). A 58-year-old female patient
      was admitted to the emergency department with somnolence, hypothermia, and
      bradycardia. Her mental status gradually worsened, resulting in a deep coma. She
      was intubated and followed in the intensive care unit, as she needed mechanical
      ventilatory assistance due to respiratory failure. She also had bilateral non
      pitting edema, a cobblestone-like appearance, and hyperkeratotic greenish-brown
      colored lesions in the pretibial and dorsal regions of the feet that were
      compatible with ENV. Hypothyroid Graves' disease is a very rare condition among
      autoimmune thyroid disorders, and ENV is an extremely rare form of TD. Here, we
      present a patient with hypothyroid Graves' disease and ENV.

PMID- 19390998
TI  - Sophistry or justice: are the two mutually exclusive?

PMID- 19390997
TI  - Changes of serum and urine neutrophil gelatinase-associated lipocalin in type-2
      diabetic patients with nephropathy: one year observational follow-up study.
AB  - We initiated the present work to explore whether neutrophil gelatinase-associated
      lipocalin (NGAL) could be used to predict the progression of diabetic nephropathy
      in type-2 diabetic patients. Seventy-four type-2 diabetic patients were divided
      into normo-, micro- and macro-albuminuria groups according to their 24 h-urinary
      albumin excreting rate. Serum and urine NGAL, and other clinical parameters were
      detected. Patients were followed and measurements were repeated 1 year later. An
      increased tendency of urine NGAL and a decreased tendency of serum NGAL were
      detected, from normo-albuminuria group to macro-albuminuria group. Serum NGAL was
      found to rise after follow-up. Moreover, urine NGAL was found to be correlated
      positively with cystatin C, urea nitrogen, and serum creatinine (SCr), and
      inversely with glomerular filtration rate (GFR), while serum NGAL correlated
      negatively with cystatin C and urea nitrogen, at both baseline and follow-up
      levels. The results indicate that NGAL correlates closely with renal function.
      Both serum and urine NGAL are sensitive for predicting the progression of type-2
      diabetic nephropathy but they may change differently. Serum NGAL may be more
      useful in early detection and urine NGAL may be more meaningful in renal function
      assessment.

PMID- 19391000
TI  - Pulse polio immunization in district Panipat: a process evaluation.
AB  - OBJECTIVE: To evaluate all steps of pulse polio immunization on special sub
      national immunization day. METHODS: On a sub-national immunization day (SNID),
      120 booths were randomly selected from 662 booths by probability proportionate to
      size (PPS) sampling technique. RESULTS: It was observed that attendance in the
      district level meeting was thin (30%). 34% workers were doing this work for the
      first time without any training. 40% of the vaccinators were neither working
      according to micro plan nor were same as mentioned in the micro plan. Supervision
      too was found deficient. CONCLUSION: In a sustained and long drawn programme like
      IPPI, sustaining the interest and motivation of health personnel is paramount.
      This paper emphasises the importance of continued re-orientation training to keep
      them motivated and updated.

PMID- 19390999
TI  - Experience with Kangaroo mother care in a neonatal intensive care unit (NICU) in
      Chandigarh, India.
AB  - OBJECTIVE: To study the feasibility and acceptability of Kangaroo mother care
      (KMC) on the low birth weight infants (LBWI) in the neonatal intensive care unit
      (NICU) by the mothers, family members and health care workers (HCW) and to
      observe its effect on the vital parameters of the babies. METHOD: A observation
      in the NICU. RESULTS: A total of 135 babies (74 boys and 61 girls) who completed
      minimum of 4 hrs of KMC/day, were included. The mean birth weight and gestation
      were 1460 gm and 30 week respectively. 47% babies started KMC within first week
      of age. Mean duration of KMC was 7 days (3-48) days. The O(2) saturation improved
      by 2-3%, temperature ( degrees C) rose from 36.75 +/- 0.19 to 37.23 +/- 0.25,
      respiration stabilized (p<0.05 for all) and heart rate dropped by 3-5 beats. No
      episodes of hypothermia or apnea were observed during KMC. KMC was accepted by 96
      % mothers, 82% fathers and 84% other family members. 94% HCW considered it to be
      safe and conservative method of care of LBWI. Benefits of KMC on the babies'
      behavior and on maternal confidence and lactation were reported by 57%, 94% and
      80% respectively. A decline in use of heating devices in the NICU was reported by
      85% and 79% said it did not increase their work load. CONCLUSION: KMC was found
      to be safe, effective and feasible method of care of LBWI even in the NICU
      settings. Positive attitudes were observed in mothers, families and HCW.

PMID- 19391001
TI  - Mineral content of complementary foods.
AB  - OBJECTIVE: To document mineral contents iron, zinc, calcium, energy contents and
      nutrient densities in complementary foods commonly given to young urban slum
      children. METHODS: Information on dietary intake was collected from 892 mothers
      of children aged 13-24 months, using 24 hour dietary recall and standardized
      measures. Three variations of 27 most commonly prepared recipes were analyzed and
      their energy (Kcal/g) and nutrient densities (mg/100 Kcal) were calculated.
      RESULTS: Considerable variations were observed in preparation of all items fed to
      the children. Cereal-based items predominated their diets with only small amount
      of vegetables/fruits. Fenugreek was the only leafy vegetable included, but was
      given to only 1-2% of children. Iron, calcium, zinc contents of staple
      complementary foods ranged from: 0.33 mg to 3.73 mg, 4 mg to 64 mg, and 0.35 mg
      to 2.99 mg/100 respectively. Recipes diluted with less water and containing
      vegetables, spices had higher mineral content. Minerals densities were higher for
      dals, fenugreek vegetable, khichdi and chapatti. Using the median amounts of the
      various recipes fed to children, intakes of all nutrients examined especially
      calcium and iron was low. CONCLUSION: There is an urgent need to educate mothers
      about consistency, dilution, quantity, frequency, method of preparation,
      inclusion of micronutrient-rich foods, energy-dense complementary foods and
      gender equality.

PMID- 19391002
TI  - A community based approach to improve health care seeking for newborn danger
      signs in rural Wardha, India.
AB  - OBJECTIVE: To find out the effect of community mobilization and health education
      effort on health care seeking behavior of families with sick newborns, and to
      explore the rationale behind the changed health care seeking behaviors of mothers
      in a rural Indian community. METHODS: In the present community based
      participatory intervention, a triangulated research design of quantitative
      (survey) and qualitative (Focus group discussions, FGDs) method was undertaken
      for needs assessment in year 2004. In community mobilization, women's self help
      groups; Kishori Panchayat (KP, forum of adolescent girls), Kisan Vikas Manch
      (Farmers' club) and Village Coordination Committees (VCC) were formed in the
      study area. The trained social worker facilitated VCCs to develop village health
      plans to act upon their priority maternal and child health issues. The pregnant
      women and group members were given health education. The Lot Quality Assurance
      Sampling (LQAS) technique was used to monitor awareness regarding newborn danger
      signs among pregnant women. In year 2007, a triangulation of quantitative survey
      and a qualitative study (free list and pile sort exercise) was undertaken to find
      out changes in health care seeking behaviors of mothers. RESULTS: There was
      significant improvement in mothers' knowledge regarding newborn danger signs.
      About half of the mothers got information from CLICS doot (female community
      health worker). The monitoring over three years period showed encouraging trend
      in level of awareness among pregnant women. After three years, the proportion of
      mothers giving no treatment/home remedy for newborn danger signs declined
      significantly. However, there was significant improvement in mothers' health care
      seeking from private health care providers for sick newborns. CONCLUSION: The
      present approach improved mothers' knowledge regarding newborn danger signs and
      improved their health care seeking behavior for newborn danger signs at community
      level. Due to lack of faith in government health services, women preferred to
      seek care from private providers.

PMID- 19391003
TI  - Stem cell through present and future.
AB  - Stem cell transplantation (SCT) has the potential to transform the lives of
      children with a wide variety of genetic diseases, ranging from inherent defects
      of hemopoietic cell production or function through to metabolic diseases mostly
      affecting solid organs. For these children life expectancy or quality of life
      would otherwise be very poor. It ranks as one of the most remarkable therapeutic
      advances of the past 40 years. Despite rapid technological improvements, however,
      there are still many short term risks and potential long term toxicities.
      Consequently, the rapid emergence of alternative therapies (including new drugs,
      enzyme and gene therapies), necessitate constant re-evaluation of the
      risk/benefit ratio for each disease and hence the appropriateness of SCT. This
      review describes the major aspects of the transplant process, indications for
      transplantation, outcome statistics, and areas where alternative therapies are
      becoming available. SCT remains a highly experimental therapy. Due to the
      relatively short history of the discipline no data exists on truly long term
      follow up. This is important as some organs benefit relatively poorly or problems
      may emerge which were never apparent as part of the untreated disease. The speed
      of technological change makes randomised trials on these diseases, which are
      individually quite rare, almost impossible to perform.

PMID- 19391004
TI  - Diagnosis and management of cyanotic congenital heart disease: part I.
AB  - Most commonly encountered cyanotic cardiac lesions in children, namely, tetralogy
      of Fallot, transposition of the great arteries and tricuspid atresia are
      reviewed. Pathology, pathophysiology, clinical features, non-invasive and
      invasive laboratory studies and management are discussed. The clinical and non
      invasive laboratory features are sufficiently characteristic for making the
      diagnosis and invasive cardiac catheterization and angiographic studies are not
      routinely required and are needed either to define features, not clearly defined
      by non-invasive studies or as a part of catheter-based intervention. Surgical
      correction or effective palliation can be undertaken with relatively low risk.
      However, residual defects, some requiring repeat catheter or surgical
      intervention, are present in a significant percentage of patients and therefore,
      continued follow-up after surgery is mandatory.

PMID- 19391006
TI  - Pulmonary arterial hypertension in children: a medical update.
AB  - Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized
      by a progressive pulmonary vasculopathy with ensuing right heart failure if left
      untreated. In the 1980's, prior to the current treatment era, idiopathic
      pulmonary arterial hypertension (IPAH) carried a poor prognosis with a 10 month
      median survival for children after diagnosis. However, in 1995 continuous
      intravenous epoprostenol was approved for the treatment of severe PAH, improving
      hemodynamics, quality of life, exercise capacity, functional class and survival.
      In the past decade there have been further advances in the treatment of PAH;
      however, there is still no cure. While much of the groundbreaking clinical
      research has been performed in adults, children have also seen the benefits of
      PAH novel therapies. The target population among pediatric patients is expanding
      with the recent recognition of pulmonary hypertension as a risk factor for sickle
      cell disease patients. With rapid advances, navigating the literature becomes
      challenging. A comprehensive review of the most recent literature over the past
      year on available and emerging novel therapies as well as an approach to target
      pediatric populations provides insights into the management of pediatric PAH
      patients.

PMID- 19391005
TI  - Kawasaki Disease update.
AB  - Kawasaki Disease is rapidly becoming the most common cause of acquired heart
      disease in children in both the developed and developing world. Its etiology
      remains a mystery but important progress has been made in characterizing the
      features of the arterial wall and myocardial pathology and long-term clinical
      consequences. New treatments aimed at modifying the host immune response are
      currently under study. The genetic influence on susceptibility and disease
      outcome is an area of active research.

PMID- 19391007
TI  - Adverse events associated with neonatal exchange transfusion for
      hyperbilirubinemia.
AB  - To estimate the incidence of blood exchange and determine causes and complication
      of blood exchange and identify strategies for risk reduction of Kernicterus in
      newborn with jaundice. From March 2004 to March 2006 in neonatal Department in
      children hospital, medical center Tehran, Iran, 346 neonates were admitted as
      neonatal jaundice without sign and symptoms of infections. We identified causes
      and complications of exchange. Of 346 infants with jaundice who received
      phototherapy. 50, 14.45 percent cases underwent exchange transfusion with mean
      age 9.38 + 5.75 days. The mean total Serum bilirubin level was 29.39 + 6.13
      mg/dl. ABO incompatibility was the most common cause for hyperbilirubinemia. The
      incidence of apnea was 12% there was no direct death from exchange transfusion.
      To make payment women aware to observe jaundice regularly after birth of their
      child and short breast feeding to control dehydration.

PMID- 19391008
TI  - Spectrum of purpura fulminans.
AB  - Purpura Fulminans is a severe disorder of acute onset with high morbidity and
      mortality. It is characterized by DIC with thrombocytopenia, hyofibrinogenemia,
      hypothrombinemia and anemia. It most often occurs in young with sudden appearance
      of symmetrical, tender, ecchymotic skin lesions usually involving the lower
      extremities. An infectious and noninfectious etiology has been proposed. Early
      recognition and early therapy with appropriate antibiotics and heparin is known
      to limit both morbidity and mortality. This article reports 5 cases of Purpura
      Fulminans treated at our centre with review of etiology, pathogenesis, clinical
      features and treatment.

PMID- 19391009
TI  - ACTH therapy in refractory generalized epilepsy.
AB  - Adrenocorticotropic hormone (ACTH) has a long track record for the treatment of
      infantile spasms. However, there is paucity of data on the use of ACTH in the
      treatment of epilepsy beyond infantile spasms. We report the use of ACTH in two
      children with refractory generalized epilepsy. Both patients responded well. ACTH
      may be considered as a useful adjunctive therapy in patients with intractable
      generalized seizures. Side effects and cost however, remain important concerns.

PMID- 19391010
TI  - Recurrent meningitis secondary to isolated C3 deficiency.
AB  - A 5-year-old child presented with the second episode of meningitis when we
      started investigating her to find a cause for recurrent episode of meningitis.
      During this she suffered from a third attack after which she was diagnosed as
      having isolated C(3) deficiency. She was put on penicillin prophylaxis and
      vaccinated against encapsulated bacteria, after which she is now doing well.

PMID- 19391011
TI  - Galactosemia with chorea--an unusual presentation.
AB  - Galactosemia, an inborn neurometabolic disorder, results from an aberrant
      galactose metabolism due to the deficiency of serum galactose-1-phosphate
      uridyltransferase activity. It manifests in the central nervous system in the
      form of hypotonia, seizures, mental retardation, tremor, ataxia, and progressive
      cerebellar as well as extrapyramidal features. To the best of our knowledge,
      chorea due to galactosemia has not been reported in infancy.

PMID- 19391012
TI  - Extrauterine Intrapartum Treatment (EXIT) in bilateral primary fetal hydrothorax.
AB  - Primary Foetal Hydrothorax (PFHT), is an intrathoracic collection of fluid in the
      fetus, which may be present on either side or even bilaterally. Advances in
      foetal diagnostics now allow consideration of the Ex-utero Intrapartum Treatment
      (EXIT) procedure for PFHT. Ex-utero Intrapartum Treatment (EXIT) allows
      therapeutic interventions on the neonate while maintaining fetoplacental
      circulation and thereby maintaining oxygenation. We report two cases of bilateral
      PFHT managed successfully with EXIT procedure.

PMID- 19391014
TI  - Subdural effusion complicating neonatal meningitis: successful treatment with
      acetazolamide.
AB  - Postmeningitis subdural effusion is rare in neonates when compared to infants and
      children. For treatment, various modalities are described. Serial subdural
      punctures and surgical drain placement are advised for cases having a mass effect
      on imaging. We report a neonate with symptomatic postmeningitis subdural
      effusion, who failed to respond to serial subdural punctures, but subsequently
      managed successfully with acetazolamide. He had no recurrence further. His
      development was normal at 18 months of age.

PMID- 19391015
TI  - Acute disseminated encephalomyelitis.

PMID- 19391016
TI  - Daily cotrimoxazole prophylaxis in HIV infected children.

PMID- 19391017
TI  - Micronutrients towards India's GDP growth--snapshot on India's quest towards
      sustainable and permanent solutions to eliminate iodine deficiency disorders.

PMID- 19391018
TI  - The relationship between anabolic androgenic steroids and muscle dysmorphia: a
      review.
AB  - This review explores the condition of muscle dysmorphia (MD) and its relationship
      with anabolic androgenic steroids (AAS). Particular emphasis is placed upon
      whether anabolic steroids are a predisposing, precipitating or perpetuating
      factor of MD. Furthermore, psychiatric complications of AAS abuse are examined.
      The current evidence from the literature suggests that AAS (ab)use is possibly a
      perpetuating factor in the evolution of MD. Psychiatric complications of AAS
      include mood and behavior changes, perceptual abnormalities, and withdrawal
      symptoms. In addition, there appears to be a credible dependence theory to AAS in
      fruition.

PMID- 19391019
TI  - Body image, disordered eating and anabolic steroid use in female bodybuilders.
AB  - Body dissatisfaction and unhealthy eating practices are common among sports and
      activities that require low body fat or low body weight for enhanced performance.
      Competitive Bodybuilding is a sport that requires participants to be
      exceptionally lean and mesomorphic, thus participants may be vulnerable to
      developing unhealthy eating and weight control practices, as well as using
      anabolic steroids. This study compares competitive female bodybuilders (CFBBs)
      and recreational female weight-training controls (RFWTs) on a broad scope of
      eating related and general psychological characteristics. Anonymous
      questionnaires, designed to assess eating attitudes, body image, weight and shape
      preoccupation, prevalence of binge eating, body modification practices (including
      anabolic steroids), lifetime rates of eating disorders, and general psychological
      characteristics, were completed by 20 CFBBs and 25 RFWTs. High rates of weight
      and shape preoccupation, body dissatisfaction, bulimic practices, and anabolic
      steroid use were reported among CFBBs, and to a lesser degree, RFWTs. Differences
      between groups on general psychological factors were not statistically
      significant and effect sizes were small. CFBBs appear to share many eating
      related features with women with bulimia nervosa but few psychological traits.
      Longitudinal research is needed to ascertain whether women with disordered eating
      or a history of bulimia nervosa disproportionately gravitate to competitive
      bodybuilding, and/or whether competitive bodybuilding fosters body
      dissatisfaction, disordered eating, bulimia nervosa, and anabolic steroid use.

PMID- 19391020
TI  - Psychological determinants of emotional eating in adolescence.
AB  - Emotional eating is conceptualized as eating in response to negative affect. Data
      from a larger study of physical activity was employed to examine the associations
      among specific emotions/moods and emotional eating in an adolescent sample. Six
      hundred and sixty-six students of diverse backgrounds from 7 middle schools in
      Los Angeles County participated. Cross-sectional analysis revealed no gender
      differences in emotional eating, and showed that perceived stress and worries
      were associated with emotional eating in the total sample. Gender stratified
      analyses revealed significant associations of perceived stress, worries and
      tension/anxiety to emotional eating for girls, while only confused mood was
      related to emotional eating in boys. These findings bear potential implications
      for the treatment and prevention of pediatric obesity and eating disorders
      because they suggest that interventions would benefit from incorporation of
      stress-reduction techniques and promotion of positive mood.

PMID- 19391021
TI  - Differential Treatment Response for Eating Disordered Patients With and Without a
      Comorbid Borderline Personality Diagnosis Using a Dialectical Behavior Therapy
      (DBT)-Informed Approach.
AB  - Studies have reported conflicting findings regarding the impact on treatment for
      eating disorder patients comorbidly diagnosed with borderline personality
      disorder. The current investigation sought to investigate whether individuals
      diagnosed with an eating disorder vs. those comorbidly diagnosed with an eating
      disorder and borderline personality disorder differ on measures of eating
      disorders symptoms and/or general distress over the course of treatment. In light
      of the success of DBT in treating individuals diagnosed with borderline
      personality disorder, a group known to have considerable difficulties in
      regulating affect, the current study also sought to examine whether these two
      groups would differ on expectancies to regulate affect over the course of DBT
      informed treatment. Results indicated that while a comorbid diagnosis of
      borderline personality disorder did not impact eating disorder treatment
      outcomes, those comorbidly diagnosed did present overall with higher levels of
      general distress and psychological disturbance. With respect to affect
      regulation, results indicated that at the beginning of treatment, eating
      disordered individuals who carried a comorbid diagnosis of BPD were significantly
      less able to regulate affect than patients without a comorbid borderline
      diagnosis. However, at the end of treatment there was no statistically
      significant difference between the two groups. The role of affect regulation in
      treating eating disordered individuals with a comorbid borderline personality
      disorder diagnosis is discussed.

PMID- 19391022
TI  - Changes in implicit and explicit measures of ego functions and distress among two
      eating disorder subgroups: outcomes of integrative treatment.
AB  - The study examined changes in ego functions and mental distress among eating
      disorder (ED) adolescent inpatients following integrative treatment. Participants
      included 31 restricting anorexia nervosa and 25 bingeing/purging spectrum ED
      inpatients. Rorschach Comprehensive System (CS; Exner, 2003) and self-report
      measures were administered on admission and discharge. We found that improvement
      in ego functions, mental distress and ED symptomatology occurred in both ED
      groups at discharge. Nevertheless, the two ED subgroups exhibited different
      configurations of change as well as varying patterns of relations between changes
      in mental distress and ego functions and improvement in ED symptoms. These data
      further indicate that the restricting and bingeing/purging patients may require
      different treatment approaches.

PMID- 19391026
TI  - A meditation on life, love and being a therapist: it's not what I expected.
AB  - Volumes have been written speculating how therapy expands the lives of clients.
      Far less is understood about the impact of doing clinical work on the therapist's
      own life. In the process of the therapeutic journey, not only do clients contact
      buried grief, but therapists too, inevitably revisit their own buried darkness,
      offering them ongoing opportunities for growth and renewal.

PMID- 19391028
TI  - Enrichment of gluten-free tarhana with buckwheat flour.
AB  - Tarhana, a traditional fermented cereal food in Turkey, is mainly prepared with
      wheat flour and yoghurt. Buckwheat is a major ingredient in the daily diet of the
      celiac patients due to its gluten-free composition. In this research, gluten-free
      tarhana samples were prepared with buckwheat flour (BWF), rice flour and corn
      starch. Control tarhana was made of wheat flour. In gluten-free formulations,
      instead of wheat flour, 40% BWF, 30% rice flour and 30% corn starch in the first
      formulation and 60% BWF, 20% rice flour and 20% corn starch in the second
      formulation were handled. BWF substitution at a 60% level increased the ash and
      fat contents of tarhana samples, but affected the lightness value of the samples
      negatively. Potassium, magnesium and phosphorus contents of the gluten-free
      tarhana increased significantly (P <0.05) with increasing amount of BWF in the
      formulation. Sensory evaluation showed that BWF addition resulted in changes in
      consistency, taste, sourness and grittiness. Tarhana containing 40% BWF received
      the highest taste and overall acceptability scores.

PMID- 19391029
TI  - Preparation of nata de coco-based carboxymethylcellulose coating and its effect
      on the post-harvest life of bell pepper (Capsicum annuum l.) fruits.
AB  - Carboxymethyl cellulose from nata de coco, referred to as carboxymethyl-nata
      (CMN), was prepared by two cycles of mercerization and etherification. Coatings
      containing 1% and 2% CMN were applied on bell peppers to evaluate the effect of
      the polysaccharide coating on the post-harvest life of the fruits. The fruits
      were stored at 25 degrees C. During storage, the color change in CMN-coated
      fruits was slower than in the control and blank fruits (coated with additives
      only). CMN-coated fruits maintained firmness and had lower weight loss, total
      soluble solids content and titratable acidity than the control and blank.
      Antioxidant activity and total phenolic content increased from day 0 to day 15.
      CMN-coated fruits had lower total phenolic content than the control and blank at
      day 15. Values at day 15 did not indicate the retardation of antioxidant activity
      in the 1% CMN-coated fruits. Results indicated that CMN coatings reduced the rate
      of ripening.

PMID- 19391030
TI  - Chemical composition and in vitro anti-inflammatory activity of apple phenolic
      extracts and of their sub-fractions.
AB  - Apple extract powders from three different manufacturers were investigated for
      their anti-inflammatory activity, their total phenolic content, and their
      chemical composition. The samples represented two production batches for two
      products and a single batch of a third. The samples showed similar, but clearly
      different, anti-inflammatory activities, and had substantially different total
      phenolic contents, and different chemical compositions. Differences in chemical
      composition for batches of the same product were significant, although not as
      great as differences between products. The samples were fractionated into
      chemical classes. The most active fractions were those that contained
      epicatechin, catechin with phloridzin and quercetin glycosides, or those that
      contained procyanidin polymers. It was not possible to link activity to the
      presence of individual components or combinations of these. If fruit extracts are
      to be reliably linked to validated health benefits, then the source materials,
      the extraction processes, and the final composition of such products need to be
      more clearly defined than at present.

PMID- 19391031
TI  - Characterization of the antioxidant properties of hydrophilic and lipophilic
      extracts of Jute (Corchorus olitorius) leaf.
AB  - Corchorus olitorius (jute) is a native plant of tropical Africa and Asia, and has
      since spread to Australia, South America and some parts of Europe. Its leafy
      vegetable is popularly used in soup preparation and folk medicine for the
      treatment of fever, chronic cystitis, cold and tumours. A comparative study of
      the antioxidant properties of hydrophilic extract (HE) and lipophilic extract
      (LE) constituents of the leafy vegetable has been assessed. HE and LE of the leaf
      were prepared using water and hexane, respectively and their antioxidant
      properties were determined. HE had a significantly higher (P<0.05) 1,1-diphenyl-2
      picrylhydrazyl radical-scavenging ability (aqueous, 9.6-84.4%; hexane, 2.0
      20.4%), reducing power (aqueous, 0.67 mmol ascorbic acid equivalent/g; hexane,
      0.49 mmol ascorbic acid equivalent/g) and trolox equivalent antioxidant capacity
      (aqueous, 2.3 mmol/g; hexane, 1.1 mmol/g) than LE; conversely, LE had a
      significantly higher (P<0.05) OH. scavenging activity (44.5-46.2%) than HE (11.6
      32.3%), while there was no significant difference (P>0.05) in their Fe(II)
      chelating ability (HE, 57.7-66.7%; LE, 56.4-61.1%). The higher 1,1-diphenyl-2
      picrylhydrazyl radical-scavenging ability, reducing power and trolox equivalent
      antioxidant capacity of the hydrophilic extract may be due to its significantly
      higher (P<0.05) total phenol (630.8 mg/100 g), total flavonoid (227.8 mg/100 g)
      and non-flavonoid polyphenols (403.0 mg/100 g), and its high ascorbic acid
      content (32.6 mg/100 g). While the higher OH. scavenging ability of LE may be due
      to its high total carotenoid content (42.5 mg/100 g). Therefore, the
      additive/synergistic antioxidant activities of the hydrophilic and lipophilic
      constituents may contribute to the medicinal properties of C. olitorius leaf.

PMID- 19391032
TI  - beta-Carotene and alpha-tocopherol in healthy overweight adults; depletion
      kinetics are correlated with adiposity.
AB  - Healthy overweight subjects (24 males, 68 females; mean age=48.8 years; body mass
      index=27.1+/-4.9) participated in a randomized, double-blind, placebo-controlled
      crossover study with two periods of 28-day supplementation using a nutritional
      product composed primarily of dehydrated juice concentrates from mixed fruits and
      vegetables (JuicePlus +). Compared with placebo, supplementation for 28 days
      increased concentrations of serum beta-carotene by 264% (P <0.001) and alpha
      tocopherol by 14% (P < 0.01). After crossover of the active group to placebo,
      beta-carotene and alpha-tocopherol declined via first-order kinetics, with serum
      half-lives (t (1/2)) for beta-carotene and alpha-tocopherol determined to be
      22.8+/-3.1 and 4.6+/-2.3 days, respectively. Depletion rates for beta-carotene
      correlated with adiposity (quartile 1, body mass index=21.96, t (1/2)=17.6 days
      vs. quartile 4, body mass index=37.87, t (1/2)=26.3 days; P < 0.05). In
      conclusion, the supplementation period resulted in significantly elevated levels
      of beta-carotene and alpha-tocopherol, indicating bioavailability. These
      increased levels persisted 2-4 weeks after supplementation was discontinued, and
      the rates of depletion were correlated with the levels of general adiposity.

PMID- 19391033
TI  - Preparation of carboplatin-Fe@C-loaded chitosan nanoparticles and study on
      hyperthermia combined with pharmacotherapy for liver cancer.
AB  - BACKGROUND: Magnetic fluid hyperthermia is a kind of technology for treating
      tumors based on nanotechnology. It is suitable to various types of tumors. The
      purpose of this study was to prepare carboplatin-Fe@C-loaded chitosan
      nanoparticles with Fe@C as a magnetic core and to investigate efficacy of
      hyperthermia combined with chemotherapy for transplanted liver cancer in rats.
      METHODS: Fe@C nanopowder was treated with dilute hydrochloric acid to prepare
      Fe@C nanocage. Carboplatin-Fe@C-loaded chitosan nanoparticles were prepared by
      reverse microemulsion method with the nanocages as the magnetic cores, chitosan
      as the matrix. The shape, size, drug-loading rate, and in vitro cumulative
      release of the nanoparticles were observed and heat product under high frequency
      alternating electromagnetic field in vitro was explored. Eighty rats with
      transplanted liver cancer were randomly divided into 4 groups (group A: control
      group, group B: free carboplatin group, group C: nanoparticles with static
      magnetic field group, and group D: nanoparticles with static field and
      alternating magnetic field). Drug was injected into the hepatic artery. The
      therapeutic effect of hyperthermia combined with chemotherapy for tumor, toxicity
      and rat survival time were observed. RESULTS: Carboplatin-Fe@C-loaded chitosan
      nanoparticles were spherical in shape with an average size of (207 +/- 21) nm and
      high saturation magnetization. The drug-loading rate of the nanoparticles was
      11.0 +/- 1.1%. The cumulative release percentage of carboplatin-Fe@C-loaded
      chitosan nanoparticles in vitro at different point time phase of 24 h, 48 h, 72
      h, 96 h and 120 h were 51%, 68%, 80%, 87% and 91%, respectively. With an increase
      in carboplatin-Fe@C-loaded chitosan nanoparticle concentration and magnetic field
      strength, the heating rate and constant temperature of carboplatin-Fe@C-loaded
      chitosan nanoparticles dispersed in physiological saline were increased in an
      alternating magnetic field. In vivo experiments showed that after particle
      injection, tumor temperature reached 42.6 degrees +/- 0.2 degrees C within 10 min
      in the alternating magnetic field; and the temperatures in the right hepatic
      lobes and the rectum were significantly lower than in the tumor and the constant
      temperature could last up to 30 min. The inhibition ratio of tumor weight in
      group D was significantly enhanced, no obviously toxic and side-effect occurred
      and survival time was prolonged. CONCLUSION: Carboplatin-Fe@C-loaded chitosan
      nanoparticles possess good magnetic targeting and heat production properties.
      They can target liver cancer tissue by static magnetic field, and with the
      application of alternating magnetic field, effectively raise tumor tissue
      temperature and facilitate tumor apoptosis. The combination of chemotherapy and
      magnetic materials into nanoparticles as described herein demonstrates promising
      efficacy.

PMID- 19391034
TI  - Meningioma 1 gene is differentially expressed in CD34 positive cells from bone
      marrow of patients with myelodysplastic syndromes with the highest expression in
      refractory anemia with excess of blasts and secondary acute myeloid leukemia.

PMID- 19391035
TI  - Polymorphisms of glutathione S-transferase Mu 1, glutathione S-transferase theta
      1 and glutathione S-transferase Pi 1 genes in Hodgkin's lymphoma susceptibility
      and progression.
AB  - We tested in this study whether the polymorphisms of the glutathione S
      transferase Mu1 (GSTM1), glutathione S-transferase Theta 1 (GSTT1) and
      glutathione S-transferase Pi 1 (GSTP1), involved in metabolism of chemical
      agents, cell proliferation and cell survival, alter the risk for Hodgkin lymphoma
      (HL). Genomic DNA from 110 consecutive patients with HL and 226 controls was
      analysed by polymerase chain reaction and restriction digestion for the
      polymorphism analyses. Similar frequencies of the GSTM1 and GSTT1 genotypes were
      seen in patients and controls. In contrast, the frequency of the GSTP1 wild
      genotype (59.1%versus 36.3%, P = 0.004) was higher in patients than in controls.
      Individuals with the wild genotype had a 2.68 (95%CI: 1.38-5.21)-fold increased
      risk for the disease than others. An excess of the GSTP1 wild genotype was also
      observed in patients with tumors of stages III + IV when compared with those with
      tumors of stages I + II (39.1%versus 20.0%, P = 0.03). These results suggest that
      the wild allele of the GSTP1 gene is linked to an increased risk and high
      aggressiveness of the HL in our cases but they should be confirmed by further
      studies with larger cohorts of patients and controls.

PMID- 19391036
TI  - Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms and
      therapy-related toxicity in children treated for acute lymphoblastic leukemia and
      non-Hodgkin lymphoma.
AB  - This study aimed to investigate the association of the methylenetetrahydrofolate
      reductase (MTHFR) gene C677T and A1298C polymorphisms with serum drug levels and
      toxicities after high-dose methotrexate (MTX) infusion. The study included 37
      children with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Serum MTX
      levels and toxicities of bone marrow, liver and kidney were analysed. Genotype
      analysis of the C677T and A1298C gene polymorphisms from genomic DNA of the
      subjects was performed by real-time PCR. Subjects with MTHFR polymorphism for
      C677T (CT, TT) had significantly higher MTX levels at 24 h (p = 0.009), and these
      genotypes did not seem to cause toxicity. Subjects with MTHFR polymorphism for
      A1298C (AC, CC) had significantly higher MTX levels at 48 h (p = 0.02), and had
      more grade III/IV anemia (p = 0.02), thrombocytopenia (p = 0.0001), elevated AST
      levels (p = 0.04) and frequent febrile neutropenic episodes (p = 0.004). The
      present study suggests that A1298C gene, but not C677T polymorphism is associated
      with MTX-related toxicity.

PMID- 19391037
TI  - Case 41. A misdiagnosis of erythroleukemia.
AB  - A 57-year-old woman with splenomegaly, moderate anemia and a paraspinal mass was
      found to have strikingly increased erythropoiesis, which was left shifted and
      dysplastic with many multinucleated cells. An increased percentage of CD34
      positive and CD117-positive cells suggested a diagnosis of pure erythroleukemia.
      Further investigations were performed.

PMID- 19391038
TI  - Dysregulation of unfolded protein response partially underlies proapoptotic
      activity of bortezomib in multiple myeloma cells.
AB  - The 26S proteasome inhibitor, bortezomib, has shown remarkable therapeutic
      efficacy in multiple myeloma (MM), however, the mechanism by which this compound
      acts remains unknown. Here, we have demonstrated that bortezomib targets the
      prototypical expression of unfolded protein response (UPR) genes BiP, CHOP and
      XBP-1 at the mRNA and protein levels, resulting in induction of proapoptotic UPR
      outputs and suppression of cytoprotective UPR components, leading to caspase
      dependent apoptosis in human MM H929 and 8226/S cell lines. Moreover, knockdown
      of XPB-1s, via lentivirus-mediated RNA interference approach, sensitises MM cells
      to apoptosis induction by bortezomib. Together, these data strongly suggest that
      dysregulated or disruptive UPR may, at least partly, underlie the antimyeloma
      activity of bortezomib.

PMID- 19391039
TI  - Dexamethasone and hypoxia upregulate CXCR4 expression in myeloma cells.
AB  - We investigated the modulation of CXCR4 expression by cytokines, dexamethasone,
      and hypoxia in myeloma cells in vitro. Tumor necrosis factor-alpha (TNF-alpha),
      transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth
      factor (VEGF) enhanced CXCR4 expression in RPMI8226 cells. In the myeloma cell
      lines examined and primary bone marrow (BM) CD138+ cells, dexamethasone enhanced
      CXCR4 expression both in the cytoplasm and on the cell surface, while
      downregulating SDF-1 expression and secretion in BM stromal cells. Incubation of
      cells under hypoxic conditions (1% O(2)) also induced upregulation of CXCR4 in
      the cytoplasm and on the cell surface and enhanced chemotaxis in response to
      stromal cell-derived factor-1 (SDF-1). Cell surface CXCR4 expression was more
      prominent in annexin V-positive apoptotic cells. Given the roles of the SDF
      1/CXCR4 axis in the development and progression of myeloma, CXCR4-downregulating
      agents may enhance the antitumor effects of dexamethasone.

PMID- 19391040
TI  - Human T-leukemia and T-lymphoma express glutamate receptor AMPA GluR3, and the
      neurotransmitter glutamate elevates the cancer-related matrix-metalloproteinases
      inducer CD147/EMMPRIN, MMP-9 secretion and engraftment of T-leukemia in vivo.
AB  - Glutamate is the major excitatory neurotransmitter of the nervous system. We
      previously found that glutamate activates normal human T-cells, inducing their
      adhesion and chemotaxis, via its glutamate receptors of the alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (AMPA) subtype 3 (GluR3) expressed in these
      cells. Here, we discovered that human T-leukemia (Jurkat) and cutaneous sezary T
      lymphoma (HuT-78) cells also express high levels of GluR3. Furthermore, glutamate
      (10 nM) elevates CD147/EMMPRIN, a cancer-associated matrix metalloproteinases
      (MMPs) inducer, promoting spread of many tumors. Glutamate-induced CD147
      elevation in both cancerous and normal human T-cells was mimicked by AMPA
      (glutamate/AMPA-receptor agonist) and blocked by CNQX (glutamate/AMPA-receptor
      antagonist). Importantly, glutamate also increased gelatinase MMP-9 secretion by
      T-lymphoma. Finally, ex vivo pre-treatment of T-leukemia with glutamate enhanced
      their subsequent in vivo engraftment into chick embryo liver and chorioallantoic
      membrane. Together, these findings reveal that glutamate elevates cancer
      associated proteins and activity in T-cell cancers and by doing so may facilitate
      their growth and spread, especially to and within the nervous system. If so,
      glutamate receptors in T-cell malignancies should be blocked.

PMID- 19391041
TI  - A combination of rituximab, cyclophosphamide and dexamethasone effectively treats
      immune cytopenias of chronic lymphocytic leukemia.
AB  - Auto-immune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP)
      are known complications of chronic lymphocytic leukemia (CLL). Rituximab,
      cyclophosphamide and dexamethasone (RCD) effectively target lymphocytes and
      inhibit autoimmune processes. We reviewed 21 patients with CLL treated for AIHA
      alone (n = 18), ITP alone (n = 1) or both (n = 2) with the following RCD regimen:
      rituximab 375 mg/m(2) i.v. infusion given on day 1, cyclophosphamide 750-1000
      mg/m(2) i.v. on day 2 and dexamethasone 12 mg day 1-7 given every 3 weeks.
      Response to treatment was seen in all 20 patients with CLL with AIHA. Median
      hemoglobin pre-treatment was 8 g/dL. The median change in hemoglobin was 5.2 g/dL
      and the median post-treatment hemoglobin level was noted to be 13.1 g/dL. Median
      duration of response was 22 months. Nine relapsed patients responded as well.
      Fifty percent of evaluable patients converted to Coombs negative with median
      duration of response of 41 months vs. 10 months for those who did not convert.
      This difference was not statistically significant (p = 0.0674). Steroid
      refractory immune thrombocytopenia was present in three patients and all
      responded to RCD. There were no hospitalisations or infections directly related
      to RCD. RCD is a safe and effective regimen in the treatment of immune cytopenias
      associated with CLL.

PMID- 19391042
TI  - Is verbal-spatial binding in working memory impaired by a concurrent memory load?
AB  - Binding processes play a critical role in memory. We investigated whether the
      binding of (visually presented) verbal and spatial (locations) information
      involves general attentional resources, as stipulated in the revised working
      memory model, by comparing measures of binding in the presence and absence of a
      concurrent memory load. Using an adaptation of a probe recognition task
      contrasting performance between intact and recombined conditions, we found that
      the concurrent retention of a sequence of three pure tones eliminated verbal
      spatial binding. The present study constitutes the first to directly measure the
      impact of a concurrent memory load on verbal-spatial binding and suggests that
      such binding may indeed recruit attentional resources, consistent with some
      recent findings in the visual-spatial binding literature.

PMID- 19391043
TI  - The limits of visual mass perception.
AB  - The theory of direct perception suggests that observers can accurately judge the
      mass of a box picked up by a lifter shown in a point-light display. However,
      accurate perceptual performance may be limited to specific circumstances. The
      purpose of the present study was to systematically examine the factors that
      determine perception of mass, including display type, lifting speed, response
      type, and lifter's strength. In contrast to previous research, a wider range of
      viewing manipulations of point-light display conditions was investigated. In
      Experiment 1, we first created a circumstance where observers could accurately
      judge lifts of five box masses performed by a lifter of average strength. In
      Experiments 2-5, we manipulated the spatial and temporal aspects of the lift, the
      judgement type, and lifter's strength, respectively. Results showed that mass
      judgement gets worse whenever the context deviates from ideal conditions, such as
      when only the lifted object was shown, when video play speed was changed, or when
      lifters of different strength performed the same task. In conclusion, observers'
      perception of kinetic properties is compromised whenever viewing conditions are
      not ideal.

PMID- 19391044
TI  - Weighting of contingency information in causal judgement: evidence of hypothesis
      dependence and use of a positive-test strategy.
AB  - Contingency is an important cue to causation. Research shows that people
      unequally weight the cells of a 2 x 2 contingency table as follows: cause
      present/effect-present (A) > cause-present/effect-absent (B) > cause
      absent/effect-present (C) > cause-absent/effect-absent (D). Although some models
      of causal judgement can accommodate that fact, most of them assume that the
      weighting of information is invariant as a function of whether one is assessing a
      hypothesized generative versus preventive relationship. An experiment was
      conducted that tested the hypothesis-independence assumption against the
      predictions of a novel weighted-positive-test-strategy account, which predicts
      hypothesis dependence in cell weighting. Supporting that account, judgements of
      hypothesized generative causes showed the standard A > B > C > D inequality, but
      judgements of hypothesized preventive causes showed the predicted B > A > D > C
      inequality. The findings reveal that cell weighting in causal judgement is both
      unequal and hypothesis dependent.

PMID- 19391045
TI  - Are memories for duration modality specific?
AB  - Four experiments examined the effects of encoding multiple standards in a
      temporal generalization task in the visual and auditory modalities both singly
      and cross-modally, using stimulus durations ranging, across different
      experiments, from 100 to 1,400 ms. Previous work has shown that encoding and
      storing multiple auditory standards of different durations resulted in systematic
      interference with the memory of the standard, characterized by a shift in the
      location of peak responding, and this result, from Ogden, Wearden, and Jones
      (2008), was replicated in the present Experiment 1. Experiment 2 employed the
      basic procedure of Ogden et al. using visual stimuli and found that encoding
      multiple visual standards did not lead to performance deterioration or any
      evidence of systematic interference between the standards. Experiments 3 and 4
      examined potential cross-modal interference. When two standards of different
      modalities and durations were encoded and stored together there was also no
      evidence of interference between the two. Taken together, these results, and
      those of Ogden et al., suggest that, in humans, visual temporal reference memory
      may be more permanent than auditory reference memory and that auditory temporal
      information and visual temporal information do not mutually interfere in
      reference memory.

PMID- 19391046
TI  - Causal conjunction fallacies: the roles of causal strength and mental resources.
AB  - In two experiments we tested the prediction derived from Tversky and Kahneman's
      (1983) work on the causal conjunction fallacy that the strength of the causal
      connection between constituent events directly affects the magnitude of the
      causal conjunction fallacy. We also explored whether any effects of perceived
      causal strength were due to graded output from heuristic Type 1 reasoning
      processes or the result of analytic Type 2 reasoning processes. As predicted,
      Experiment 1 demonstrated that fallacy rates were higher for strongly than for
      weakly related conjunctions. Weakly related conjunctions in turn attracted higher
      rates of fallacious responding than did unrelated conjunctions. Experiment 2
      showed that a concurrent memory load increased rates of fallacious responding for
      strongly related but not for weakly related conjunctions. We interpret these
      results as showing that manipulations of the strength of the perceived causal
      relationship between the conjuncts result in graded output from heuristic
      reasoning process and that additional mental resources are required to suppress
      strong heuristic output.

PMID- 19391047
TI  - It's not what you play, it's how you play it: timbre affects perception of
      emotion in music.
AB  - Salient sensory experiences often have a strong emotional tone, but the
      neuropsychological relations between perceptual characteristics of sensory
      objects and the affective information they convey remain poorly defined. Here we
      addressed the relationship between sound identity and emotional information using
      music. In two experiments, we investigated whether perception of emotions is
      influenced by altering the musical instrument on which the music is played,
      independently of other musical features. In the first experiment, 40 novel
      melodies each representing one of four emotions (happiness, sadness, fear, or
      anger) were each recorded on four different instruments (an electronic
      synthesizer, a piano, a violin, and a trumpet), controlling for melody, tempo,
      and loudness between instruments. Healthy participants (23 young adults aged 18
      30 years, 24 older adults aged 58-75 years) were asked to select which emotion
      they thought each musical stimulus represented in a four-alternative forced
      choice task. Using a generalized linear mixed model we found a significant
      interaction between instrument and emotion judgement with a similar pattern in
      young and older adults (p < .0001 for each age group). The effect was not
      attributable to musical expertise. In the second experiment using the same
      melodies and experimental design, the interaction between timbre and perceived
      emotion was replicated (p < .05) in another group of young adults for novel
      synthetic timbres designed to incorporate timbral cues to particular emotions.
      Our findings show that timbre (instrument identity) independently affects the
      perception of emotions in music after controlling for other acoustic, cognitive,
      and performance factors.

PMID- 19391050
TI  - Variation in subjective oral health indicators of 65-year-olds in Norway and
      Sweden.
AB  - OBJECTIVE: Guided by the conceptual framework of Gilbert and co-workers, this
      study assesses satisfaction with oral health as reported by 65-year-olds in
      Sweden and Norway, the relationship of socio-demographic factors, clinical and
      subjective oral health indicators with satisfaction of oral health, and the
      consistency of those relationships across countries. MATERIAL AND METHODS: In
      2007, standardized questionnaires were mailed to all the residents in two
      counties in Sweden and three in Norway who were born in 1942. Response rates were
      73.1% (n=6078) in Sweden and 56.0% (n=4062) in Norway. RESULTS: Totals of 76.8%
      of the Swedish and 76.5% of the Norwegian participants reported satisfaction with
      oral health. Corresponding figures for toothache were 48.1% (Sweden) versus 51.5%
      (Norway), and for temporomandibular joint symptoms, 10.9% (Sweden) versus 15.1%
      (Norway). Multiple logistic regression analysis revealed that subjects who
      perceived they had bad health, smoked daily, had missing teeth, experienced
      toothache, had problems with chewing, bad breath, and oral impacts were less
      likely than their counterparts in the opposite groups to be satisfied with their
      oral health status. The corresponding odds ratios (ORs) ranged from 0.08
      (problems chewing) to 0.2 (oral impact). No statistically significant two-way
      interactions occurred and the model explained 46% of the variance in satisfaction
      with oral health across the two countries (45% in Sweden and 47% in Norway).
      CONCLUSIONS: The oral condition of 65-year-olds in Norway and Sweden produced
      impacts in oral symptoms, functional limitations, and problems with daily
      activities that varied to some extent. Satisfaction with oral health varied by
      socio-demographic factors and subjective oral health indicators. A full
      understanding of the oral health and treatment needs of 65-year-olds cannot be
      captured by clinical measures alone.

PMID- 19391051
TI  - Does a specific dental amalgam syndrome exist? A comparative study.
AB  - OBJECTIVE: The aim of this article was to investigate whether there is evidence
      for a specific syndrome of health problems attributed to dental amalgam. MATERIAL
      AND METHODS: A secondary and retrospective analysis of two different databases
      was performed: (a) 90 patients (47% female, mean (SD) age 34 (6) years) of a
      clinical trial to remove amalgam fillings who attribute their health complaints
      to dental amalgam, and (b) 116 patients (62% female, mean (SD) age 37 (8) years)
      from an outpatient unit for environmental medicine who attribute their symptoms
      to environmental sources other than amalgam. RESULTS: The samples differed in
      age, sex, and educational level. No statistically significant differences between
      either of the groups were found in overall psychological distress, intensity of
      the symptoms, or in numbers of self-reported symptoms in the Symptom Check List
      after controlling for age, sex, and education (Mean Global Severity Index 0.62
      versus 0.63). Patients from the amalgam group showed mean values for private and
      public self-consciousness similar to the population norm, while patients from the
      comparison group had statistically significantly decreased mean values. While the
      amalgam group more frequently reported mental symptoms, patients from the
      comparison group had a higher prevalence of somatic symptoms. CONCLUSIONS: The
      results showed some differences in symptomatology, while general psychological
      distress was similar in both groups, indicating no strong evidence for an amalgam
      specific syndrome.

PMID- 19391052
TI  - Reperfusion therapy for acute ST-elevation and non ST-elevation myocardial
      infarction: what can be achieved in daily clinical practice in unselected
      patients at an interventional center?
AB  - BACKGROUND: In the year 2000 a new definition of acute myocardial infarction
      (AMI) was introduced, now differentiating ST segment elevation AMI (STEMI) from
      non-ST segment elevation AMI (NSTEMI). The characterization of AMI patients
      according to this definition is still incomplete. METHODS AND RESULTS: 888
      consecutive AMI patients at a single interventional center were included: 493
      (55.5%) STEMI and 395 (44.5%) NSTEMI patients. Median age of STEMI patients was
      four years lower compared to NSTEMI patients (62.8 versus 66.6 years, P<0.001).
      STEMI patients more often presented in cardiogenic shock (11.0% versus 2.0%,
      P<0.001) and after pre-hospital resuscitation (4.9% versus 0.8%, P<0.001).
      Catheterization was performed in 98.4% of STEMI and in 95.9% of NSTEMI patients
      (P<0.001). The circumflex artery was more often the culprit lesion in NSTEMI
      patients compared to STEMI patients (58.3% versus 48%, P=0.003). They also showed
      significantly more often a 3 vessel disease (41.4% versus 29.9%, P=0.002). Out of
      STEMI patients 10.1% were treated with medical therapy only compared to 27.2% of
      NSTEMI patients (P<0.001). Whereas PCI was performed more often in STEMI patients
      (84.3% versus 57.8%, P<0.001), CABG was used more often in NSTEMI patients (21.6%
      versus 9.1%, P<0.001). In-hospital death was 8.7% in STEMI compared to 4.8% in
      NSTEMI patients (P<0.001). CONCLUSIONS: In clinical practice STEMI and NSTEMI
      seem to occur with similar frequency. Invasive strategies were applied in a high
      percentage in both groups, however with different therapeutic consequences. In
      hospital mortality was twice as high in STEMI compared to NSTEMI patients.

PMID- 19391053
TI  - Women with prehypertension in primary care - Risk profile on the basis of
      selected cardiovascular risk factors.
AB  - BACKGROUND: Demographic, social and economic trends will serve to increase the
      importance of women as healthcare consumers. Design. The aim of the study was to
      assess cardiovascular (CV) risk in the normotensive female patients during single
      visit to primary care (PC) offices. METHODS: Demographic data, history of
      coronary heart disease (CHD), diabetes (DM), smoking habit and family history of
      CV diseases were obtained from women who visited general practitioners. Moreover,
      blood pressure (BP), pulse rate, weight and height used to calculation body mass
      index (BMI) and waist circumference (WC) were performed. Prehypertension was
      defined as a systolic BP (SBP) of 120-139 mmHg, and/or a diastolic BP (DBP) of 80
      89mmHg. RESULTS: Prehypertension was observed in 21.5% of the whole group of
      female PC patients. SBP, DBP, BMI and WC revealed significant trends towards
      increase with age among both prehypertensives (p<0.001) and normotensives (SBP,
      BMI, WC: p<0.001; DBP: p<0.05) and in the whole group (p<0.001). Nevertheless,
      heart rate (HR) significantly increased with age only among prehypertensive women
      (p<0.05). The CV risk of the studied adult women increased progressively with
      presence of overweight, obesity and visceral obesity. The CV risk of the youngest
      groups was associated mainly with high prevalence of smoking, and with high
      prevalence of CHD and DM among the oldest female patients. CONCLUSIONS: The
      prevalence of majority of CV risk factors increase with age among both
      prehypertensive and normotensive women, which should stimulate PC practitioners
      to identify and modify them.

PMID- 19391054
TI  - The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch
      carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage,
      antioxidants, invasion and angiogenesis.
AB  - The neem tree has attracted considerable research attention as a rich source of
      limonoids that have potent antioxidant and anti-cancer properties. The present
      study was designed to evaluate the chemopreventive potential of the neem
      limonoids azadirachtin and nimbolide based on in vitro antioxidant assays and in
      vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster
      buccal pouch (HBP) carcinogenesis. Both azadirachtin and nimbolide exhibited
      concentration-dependent anti-radical scavenging activity and reductive potential
      in the order: nimbolide > azadirachtin > ascorbate. Administration of both
      azadirachtin and nimbolide inhibited the development of DMBA-induced HBP
      carcinomas by influencing multiple mechanisms including prevention of
      procarcinogen activation and oxidative DNA damage, upregulation of antioxidant
      and carcinogen detoxification enzymes and inhibition of tumour invasion and
      angiogenesis. On a comparative basis, nimbolide was found to be a more potent
      antioxidant and chemopreventive agent and offers promise as a candidate agent in
      multitargeted prevention and treatment of cancer.

PMID- 19391055
TI  - Ion channel modulators mediated alterations in NO-induced free radical generation
      and neutrophil membrane potential.
AB  - The present study investigated the effect of various ion (H+ and K+) channel
      modulators on nitric oxide (NO) donors (SNP and SNAP) induced free radical
      generation and on neutrophil membrane potential. Free radical generation was
      assessed by DCDHF-DA, using flow cytometry, while membrane potential was measured
      by a fluorescent dye, DiO-C5-(3). Neutrophil suspension in high potassium
      containing medium or following addition of NO donors (SNP, SNAP) to the
      neutrophil suspension led to free radical generation and membrane depolarization.
      DPI (a dual inhibitor of NADPH-oxidase and NOS), ABAH (MPO inhibitor) and BAPTA
      AM (calcium chelator) significantly reduced 80 mM KCl or NO mediated free radical
      generation. Modulators of large (NS1619), intermediate (Chlorzoxazone) and small
      conductance (Apamin, chlorzoxazone) calcium activated K+ channels (TBA), voltage
      activated K+ channels (Kv) (4AP, 8Br-cGMP), ATP sensitive K+ channels (K(ATP))
      (Glybenclamide, pinacidil), Na+,K+-ATPase (Ouabain) and Na+/H+ exchanger (NHE,
      Amiloride) altered NO-induced neutrophil free radical generation response and
      membrane polarity. The results obtained thus suggest an association between rat
      neutrophil membrane depolarization and NO-dependent free radical generation.

PMID- 19391056
TI  - Role of the 585-nm pulsed dye laser in the treatment of acne in comparison with
      other topical therapeutic modalities.
AB  - BACKGROUND: Acne vulgaris is a disease of the pilosebaceous unit characterized by
      the development of inflammatory and/or non-inflammatory lesions that may progress
      to scars. The increase of bacterial resistance and adverse effects, the
      teratogenicity of retinoids and lack of response to usual therapies has led to
      the investigation of new therapeutic alternatives. OBJECTIVE: To evaluate the
      role of the pulsed dye laser in the treatment of acne in comparison with other
      topical therapeutic modalities. METHODS: We studied 45 patients with mild to
      moderate acne. Patients were randomly divided into three groups: group A received
      treatment with pulsed dye laser therapy every 2 weeks, group B received topical
      preparations and group C was subjected to chemical peeling using trichloroacetic
      acid 25%. RESULTS: At 12 weeks of treatment, there was a significant improvement
      of the lesions within each group with the best results seen in group A; however,
      no significant difference was detected between the three treatment protocols
      after the treatment period. Remission in the follow-up period was significantly
      higher in the first group. CONCLUSIONS: Pulse dye laser therapy mainly improves
      the inflammatory lesions of acne with few adverse effects.

PMID- 19391057
TI  - Chalazion surgery: advantages of a subconjunctival approach.
AB  - The meibomian glands, present within the tarsus, produce an oily fluid which is
      part of the tear film. The obstruction of this gland is common, and results in a
      meibomian cyst or chalazion. Initially, a chalazion may spontaneously resolve, or
      respond to conservative measures such as warm compresses and topical antibiotics.
      However, sometimes the lesion becomes persistent and prominent, leading to visual
      and aesthetic problems, requiring a surgical solution. We report a 23-year-old
      man, with a right lower eyelid chalazion, persisting for more than 1 year,
      refractory to local measures that was submitted to surgical correction via the
      subconjunctival approach. This report emphasizes the advantages of this
      technique, namely the fast and simple procedure, with an excellent cosmetic
      result.

PMID- 19391058
TI  - A study to determine the effect of combination blue (415 nm) and near-infrared
      (830 nm) light-emitting diode (LED) therapy for moderate acne vulgaris.
AB  - BACKGROUND AND OBJECTIVE: Acne vulgaris remains a major problem in dermatological
      practice. Phototherapy for acne with blue (415 nm) and red (633 nm) light
      emitting diode (LED) arrays has recently attracted attention. This pilot study
      assessed the efficacy of the combination of 415 nm and near-infrared (IR) LED
      therapy for moderate acne. METHODS: Seventeen individuals were recruited: 13
      females and four males. Skin types ranged from type II to type VI, and the acne
      grades at baseline ranged from Burton grade 1 to 5. Patients underwent twice
      weekly 20-minute sessions of LED therapy for 4 weeks, alternating between the
      blue (415 nm) and near-IR (830 nm) heads. No other treatment was allowed. Results
      were assessed and compared with the baseline values at 1, 4 and 8 weeks post
      treatment. RESULTS: Six individuals failed to complete the study. Eleven
      individuals showed improvement ranging from 0% to 83.3%. A downward shift in the
      Burton grade was seen overall. Non-inflammatory lesion counts increased in four
      patients, but improved in the other seven by an average of 48.8%. No adverse
      effects were reported. CONCLUSIONS: The combination therapy for acne produced
      results which were less effective in the reduction of inflammatory lesions than
      those achieved with the previously reported blue/red combination. Further study
      with a much larger patient population is warranted.

PMID- 19391059
TI  - Experience with repetitive use of pimecrolimus: exploring the effective and safe
      use in the treatment of relapsing seborrheic dermatitis.
AB  - BACKGROUND: Seborrheic dermatitis (SD) tends to reoccur frequently, so the
      therapeutic agent must have a high benefit versus adverse effect ratio for long
      term and repetitive uses. OBJECTIVE: To assess the efficacy and safety of
      retreatment with pimecrolimus in SD patients. METHODS: A total of 45 patients who
      had been treated previously with pimecrolimus 1% cream were retreated with the
      same agent using the same treatment protocol after the disease reoccurred. The
      first and the second treatments were compared with regard to disease severity
      before treatment, complete cure times, remission times and side effects. RESULTS:
      The median severities of the disease were 5 and 4 before the first and second
      treatments, respectively. Retreatment of the disease with pimecrolimus resulted
      in shorter cure and longer remission times. Side effects were seen only on the
      first day of the retreatment and an increase in erythema was seen in fewer
      patients. CONCLUSIONS: Retreatment of the recurrence of SD with pimecrolimus as
      monotherapy is an effective and safe approach in the management of the disease.

PMID- 19391060
TI  - "You may wade through them without seeing them": general practitioners and their
      young patients with mental health problems.
AB  - OBJECTIVE: To gain insight into the management of children and adolescents with
      mental health problems by their GPs as the GPs describe it. DESIGN: A qualitative
      analysis of data from focus group interviews with GPs. SETTING: Western Coast of
      Norway. SUBJECTS: A strategic sample of 19 GPs. RESULTS: According to the
      informants psychosomatic and other internalizing disorders are the most frequent
      mental health problems in their practice. Their assessments were based on history
      taking, physical examination and acquired knowledge of development and prevalence
      of common health problems. Their interventions mostly consisted of parental
      counselling. Their assessments and interventions to a lesser extent relied on
      specific knowledge in child and adolescent psychiatry. CONCLUSION: The interested
      GP is in a good position to provide services to these patients. They have the
      parents' trust, insight into family and local community, and essential general
      medical knowledge about management of mental health problems in this age group.
      There is need for mutual research and educational programmes between GPs and
      child and adolescent psychiatry to explore the interface between the fields.

PMID- 19391061
TI  - Evaluation and advantages of an automatic magnetic mixing of syringes integrated
      to a whole blood gas analyser.
AB  - BACKGROUND: Arterial blood gases are essential for the diagnostic and therapeutic
      management of severely ill patients. The pre-analytic phase is crucial to the
      quality and interpretation of the results. Whole blood specimens used for blood
      gas analysis must be thoroughly mixed prior to analysis. Producing a homogeneous
      sample is important to obtain accurate results. The availability of a new system
      able to automate the standardization of the sample mixing would be a way to
      improve this step. We evaluated the quality of automatic mixing with the use of
      SafePICO syringes and ABL 825 FLEX blood-gas analyser. METHODS: Quantitative
      measurements of total hemoglobin and potassium were performed on ABL 825 FLEX
      from 216 whole blood specimens collected in SafePICO syringes and were compared
      with those obtained with LH 750 for hemoglobin and LX 20 for potassium. RESULTS:
      Quantitative results showed excellent agreement with a reference analyser for the
      analytes with correlation coefficients greater than 0.97. No bias was observed
      for hemoglobin and the small difference observed for potassium is not clinically
      significant and was not due to hemolysis but to the differences between the
      methods. CONCLUSIONS: ABL 825 FLEX produces a homogeneous specimen which
      minimizes the pre-analytical errors manipulator dependent.

PMID- 19391062
TI  - Impact of atrial fibrillation on NT-proBNP levels in a 75-year-old population.
AB  - OBJECTIVE: The objective of this study was to investigate the impact of atrial
      fibrillation (AF) on serum levels of N-terminal fragment of pro-brain natriuretic
      peptide (NT-proBNP) in a 75-year-old population. METHODS: All 75-year-old
      citizens in Asker and Baerum counties in Norway were invited to participate in a
      prevalence study of AF. Blood samples for measurement of NT-proBNP were collected
      at rest from 61 subjects with AF and a gender-matched control group of 126
      subjects in sinus rhythm. NT-proBNP was measured in serum using the Elecsys
      proBNP sandwich immunoassay (Roche Diagnostics, Basel, Switzerland). RESULTS:
      Subjects with permanent AF had higher levels of NT-proBNP (median 1119 pg/mL
      (interquartile range 701, 1643)) than subjects with paroxysmal AF (257 pg/mL
      (169, 382)) and controls (95 pg/mL (60, 171)), p<0.001 for both.The presence of
      AF was still significantly associated with higher log NT-proBNP (B=0.61, p<0.001)
      after adjusting for the presence of heart failure, coronary heart disease and
      hypertension. CONCLUSION: In this stable, out-of-hospital population of 75-year
      old subjects, AF was independently associated with increased levels of NT-proBNP.
      Permanent AF was associated with higher NT-proBNP levels than paroxysmal AF.

PMID- 19391063
TI  - Gene expression in Barrett's esophagus: laser capture versus whole tissue.
AB  - OBJECTIVE: Diagnosis of Barrett's esophagus (BE) is typically done through
      morphologic analysis of esophageal tissue biopsy. Such samples contain several
      cell types. Laser capture microdissection (LCM) allows the isolation of specific
      cells from heterogeneous cell populations. The purpose of this study was to
      determine the degree of overlap of the two sample types and to define a set of
      genes that might serve as biochemical markers for BE. MATERIAL AND METHODS:
      Biopsies were obtained from regions of the glandular tissue of BE and normal
      esophagus from 9 subjects with BE. Samples from 5 subjects were examined as whole
      tissue (BE [whole]; E [whole]), and in 4 subjects the glandular epithelium of BE
      was isolated using LCM (BE [LCM]) and compared with the averaged values (E [LCM])
      for both basal cell (B [LCM]) and squamous cell (S [LCM]) epithelium. RESULTS:
      Gene expression revealed 1797 probe sets between BE [whole] and E [whole] (fold
      change > 2.0; p<0.001). Most of these genes (74%) were also differentially
      expressed between BE [LCM] and E [LCM], showing that there was high concordance
      between the two sampling methods. LCM provided a great deal of additional
      information (2113 genes) about the alterations in gene expression that may
      represent the BE phenotype. CONCLUSIONS: There are differences in gene expression
      profiles depending on whether specimens are whole tissue biopsies or LCM
      dissected. Whole tissue biopsies should prove satisfactory for diagnostic
      purposes. Because the data from LCM samples delineated many more Barrett's
      specific genes, this procedure might provide more information regarding
      pathogenesis than would whole tissue material.

PMID- 19391064
TI  - Serum fatty acid profile in celiac disease patients before and after a gluten
      free diet.
AB  - OBJECTIVE: Celiac disease (CD) is characterized by villous atrophy with crypt
      hyperplasia and inflammation of the small intestinal mucosa leading to disturbed
      epithelial transport. In untreated CD, fat malabsorption can occur. The aim of
      this study was to investigate the profile of serum fatty acids in newly detected
      CD before and after treatment with a gluten-free diet. MATERIAL AND METHODS:
      Serum samples were obtained from 50 adults with active CD showing small-bowel
      mucosal villous atrophy, from the same patients in remission after treatment with
      a gluten-free diet, and from 59 controls. Serum fatty acids were analyzed by
      capillary gas-liquid chromatography. RESULTS: Especially the proportions of
      arachidonic acid (20:4 n-6) and the long-chain polyunsaturated fatty acids of the
      n-3 family docosapentaenoic acid (22:5 n-3) and docosahexaenoic acid (22:6 n-3)
      were decreased in subjects with active CD. Serum levels of these fatty acids
      increased during remission, but still remained significantly lower than control
      values. Levels of unsaturated and monounsaturated fatty acids were generally
      increased in subjects with CD compared with those in controls. CONCLUSIONS: In
      patients with CD, determination of serum fatty acid composition can be considered
      if the dietary history or symptoms suggest an inadequate supply of long-chain
      fatty acids.

PMID- 19391065
TI  - Role of serum prothrombin induced by vitamin K absence or antagonist-II in the
      early detection of hepatocellular carcinoma in patients with chronic hepatitis B
      virus infection.
AB  - OBJECTIVE: The role of serum prothrombin induced by vitamin K absence or
      antagonist-II (PIVKA-II) in the early detection of hepatocellular carcinoma (HCC)
      in patients with chronic hepatitis B virus (HBV) infection has not yet been
      clearly identified. The purpose of the study was to evaluate the sensitivity and
      specificity of PIVKA-II, alone or in combination with alpha-fetoprotein (AFP),
      for the detection of HCC during surveillance, and to determine whether PIVKA-II
      was a significant risk factor for patient survival. MATERIAL AND METHODS: During
      surveillance, 106 HCC cases and 100 non-HCC cases of chronic HBV infection were
      included. Sensitivity and specificity of AFP and PIVKA-II were obtained through
      cut-off values of 20 ng/ml and 40 mAU/ml, respectively. The Cox proportional
      hazards model was used to determine whether PIVKA-II would be a significant risk
      factor for patient survival. RESULTS: The sensitivity rates of AFP and PIVKA-II
      were 57.5% (61/106) and 51.9% (55/106), respectively. Of 45 patients negative for
      AFP, 22 were positive for PIVKA-II. A combination of AFP and PIVKA-II increased
      the sensitivity to 78.3% (83/106). The specificities of AFP and PIVKA-II were
      88.0% and 97.0%, respectively. PIVKA-II was not a significant risk factor for
      patient survival after multivariate analysis. CONCLUSIONS: PIVKA-II can be used
      as a tumor marker for the early detection of HCC in patients with chronic HBV
      infection, especially in combination with AFP.

PMID- 19391067
TI  - [Physical and technical quality assurance in German breast cancer screening:
      progress report of the Reference Center Muenster after three years].
AB  - PURPOSE: German breast cancer screening is monitored by a large physical quality
      assurance program. This report refers to the first experiences of the Reference
      Center (RC) Muenster after three years of the technical quality control of
      digital and analog mammography units (MU). This paper also shows whether the
      presently used quality assurance (QA) method is able to ensure that the MUs in
      the screening program are functioning without any serious problems. MATERIALS AND
      METHODS: RC Muenster supervises 95 units (May 2008). The daily, weekly and
      monthly quality assurance of these units is controlled by web-based QA software
      named "MammoConrol" and developed by RC Muenster. The annual QA for the units
      must be conducted in the form of an on-site inspection by medical physics experts
      of the RC and is scored by an objective ranking system. The results of these QA
      routines were evaluated and analyzed for this paper. RESULTS: During the period
      from 3/1/2006 to 5/31/2008, 8 % of the analog systems and 1 % of the digital
      systems exhibited problems in the daily QA. For 9 % of the analog MUs and 17 % of
      the digital MUs, failures appeared in the monthly QA. In the annual control, 86.7
      % of the analog units exhibited slight problems and 13.3 % had serious problems.
      With respect to the digital units, 12 % were without any defects, 58 % had slight
      problems, 27 % had serious failures and 3 % had to be reported to the responsible
      authorities and were temporarily shut down. CONCLUSION: The special quality
      control requirements for German breast cancer screening, including annual on-site
      checks of the units, have shown in the last three years that QA with a high
      monitoring standard can be ensured for a large number of decentralized MUs. The
      currently used QA method sufficiently ensures that the screening program is
      technically safe. Further studies must show whether the density and focus of the
      QA measures must be reconfigured.

PMID- 19391068
TI  - [Radiation exposure of children in pediatric radiology. Part 5: organ doses in
      chest radiography].
AB  - PURPOSE: Reconstruction of organ doses of selected organs and tissues from
      radiographic settings and exposure data collected during chest X-ray examinations
      of children of various age groups performed in Dr. von Hauner's Kinderspital
      (children's hospital of the University of Munich, DvHK) between 1976 and 2007.
      MATERIALS AND METHOD: The dosimetric data of all X-ray examinations performed
      since 1976 at DvHK were stored electronically in a database. After 30 years of
      data collection, the database now includes 305 107 radiological examinations
      (radiographs and fluoroscopies), especially 119 150 chest radiographs of all age
      groups. Reconstruction of organ doses in 40 organs and tissues in X-ray
      examinations of the chest was performed based on the conversion factor concept.
      RESULTS: The radiation exposure of organs in projection radiography is determined
      by the exact site of the organs relative to the edges of the X-ray field and the
      beam direction of X-rays. Optimal collimation in chest radiography can reduce the
      exposure of organs located at the periphery of the X-ray field, e. g. thyroid
      gland, stomach and partially the liver, by a factor of 2 to 3, while organs
      located in the center of the X-ray-field, e. g. thymus, breasts, lungs, esophagus
      and red bone marrow, are not affected by exact collimation. CONCLUSIONS: The high
      frequency of the roentgen examination of the chest in early age groups increases
      the collective radiation burden to radiosensitive organs. Therefore, radiation
      protection of the patient during chest radiographies remains of great importance.

PMID- 19391069
TI  - [Dorsal dislocation of the os trapezoideum--a rare form of carpal dislocation].

PMID- 19391071
TI  - [Current opinion in treatment of soft tissue sarcoma].
AB  - The present work discusses soft tissue sarcoma in the head and neck area, due to
      the rare occurrence and the sparse data situation is still a large number of
      unexplained riddles. The head and neck surgeon plays the central role in the
      diagnosis and treatment of the vast majority of soft tissue sarcoma in the head
      and neck area. It is crucial that these tumors immediately should be send to
      specialized centers. An larger excisional biopsy should be avoided. When
      histology and tumor extension are secured an interdisciplinary treatment concept
      should be discussed, or the patient if possible will be introduced in ongoing
      clinical studies.

PMID- 19391073
TI  - [Expert testimony: preconditions in noise-induced hearing loss].

PMID- 19391074
TI  - [Antibiotic treatment of the head and neck infections. Consensus Report on behalf
      of the Presidency of the German Society of Oto-Rhino-Laryngology, Head and Neck
      Surgery].

PMID- 19391075
TI  - [Conservative therapy of the chronic rhinosinusitis].
AB  - Chronic inflammation of nasal mucosa and sinuses are of increasing prevalence.
      Patients suffering from chronic rhinosinusitis (CRS) are characterised by nasal
      obstruction and secre- tion, impaired sense of smell, head and facial pain,
      causing impact on quality of life as well as tremendous socioeconomic effects.
      Therefore, effective and specific diagnostics as well as therapies are essential,
      which have to be selected from state of the art, evidence based guidelines.
      According to EP3OS guidelines from 2007 the CRS is defined as chronic
      inflammation of the nose and nasal sinuses, with or without nasal polyps
      (CRSwNP/CRSsNP). Upon shown diagnostic criteria of CRS first choice of therapy
      should be topical glucocorticoids causing anti-inflammatory and curative effects.
      Improvement of nasal symptoms can be achieved by hypertonic salt solutions.
      Median to severe symptoms of CRSsNP might be improved by longterm-treatment with
      oral macrolides. Patients suffering additionally from allergies will benefit from
      antihistamines, whereas those suffering from analgesic-intolerance (AI) will show
      improvement upon adaptive desensitisation. Leukotriene receptor antagonists, anti
      IgE-antibodies (Omalizumab) or anti-interleukin-5- antibodies (Mepolizumab) are
      new therapeutic options for the treatment of CRS. This paper reviews recent
      pharmacologic and non-pharmacologic therapeutic options for conservative
      treatment of CRS. In addition, evidence based therapeutic options of CRS
      treatment are evaluated.

PMID- 19391076
TI  - Pheochromocytomas: from genetic diversity to new paradigms.
AB  - Pheochromocytomas and paragangliomas are catecholamine-secreting tumors of neural
      crest origin caused by germline mutations in at least six distinct genes. This
      genetic heterogeneity has provided a rich source for both the discovery and
      functional characterization of new tumor-related genes. However, the genetic
      repertoire of these tumors is still not fully known, and current evidence points
      to the existence of additional pheochromocytoma susceptibility genes. Here, the
      unique contributions of three hereditary models of pheochromocytoma that can
      advance our knowledge of the disease pathogenesis are presented. The first model,
      loss of succinate dehydrogenase (SDH) function, illustrates how SDHB, C, or D
      mutations, components of the energy metabolism pathway, serve as a unique system
      to explore the pervasive metabolic shift of cancer cells towards glycolysis as a
      source of energy (also known as the Warburg effect) in contrast to the
      characteristic oxidative phosphorylation of normal cells. In the second model,
      mechanisms of tumorigenesis distinct from classical pheochromocytoma
      susceptibility genes are discussed in the context of a novel putative suppressor
      of neural crest-derived tumors, the KIF1B beta gene. Finally, NF1 loss is
      highlighted as a valuable study model to investigate the cell lineage selectivity
      of the Egln3-mediated developmental apoptotic defect of chromaffin precursor
      cells. Results from these studies may offer clues to understand the tissue
      specificity of hereditary pheochromocytoma syndromes. These distinct hereditary
      disease models illustrate how genetic-driven progress has the potential to narrow
      current gaps in our knowledge of pheochromocytoma and paraganglioma pathogenesis.

PMID- 19391077
TI  - An Intronic mutation is associated with prolactinoma in a young boy, decreased
      penetrance in his large family, and variable effects on MEN1 mRNA and protein.
AB  - Prolactinomas are rare tumors in prepubertal children. A prolactinoma in a young
      child may be due to sequence variants in genes that are known to cause these
      tumors ( MEN1, PRKAR1A, AIP). An 11-year-old boy with a macroprolactinoma was
      treated with cabergoline and the tumor receded. We studied the patient and his
      family for genetic causes of this tumor. No mutations were present in the coding
      sequence of PRKAR1A and AIP. A novel heterozygous substitution (IVS3-7 c>a) was
      identified in intron 3 of MEN1. We also found an additional PCR amplicon that
      incorporated the entire intron 3 of the gene (210 bp) in the patient's cDNA. The
      same amplicon was present with lower intensity in some of the control individuals
      who were not mutation carriers. Intron 3 harbors an in-frame stop codon and its
      incorporation is predicted to result in a prematurely terminated protein. We
      conclude that a novel MEN1 variation was identified in a young boy with
      prolactinoma and six of his relatives who did not present with prolactinoma or
      other MEN1 related symptoms. This novel MEN1 variation may be associated with low
      penetrance of the disease. The IVS3-7 c>a defect is suggested to be pathogenic
      because it is associated with lower menin levels in the cells of these patients,
      but its consequences may be mitigated by a variety of factors including changes
      in transcription and translation of the MEN1 gene.

PMID- 19391078
TI  - Polymorphisms of the vitamin D receptor gene and stress fractures.
AB  - Our aim was to evaluate the association between VDR polymorphisms and calcaneal
      Stiffness Index (SI) with stress fractures in a case control study including male
      military personnel. Thirty- two patients with stress fractures were matched with
      32 uninjured healthy volunteers (controls), by gender, age, height, body weight,
      and level of physical activity. The two groups were genotyped for the FokI, BsmI,
      ApaI, and TaqI polymorphisms of the VDR gene with PCR-RFLP method. In addition,
      calcaneal SI was measured by heel quantitative ultrasound in both groups. Data
      were analyzed by chi-squared test and logistic regression analysis. The f allele
      was significantly more frequent in patients than in controls (p=0.013), while the
      B allele showed such a tendency without reaching statistical significance
      (p=0.052). Among the entire cohort, a 2.7-fold and a 2.0-fold increase in risk of
      stress fractures was associated with the f and B alleles (OR, 2.7, 95% CI, 1.2
      5.9; p=0.014 and OR, 2.0, 95% CI, 1.0-4.1; p=0.053, respectively). No
      statistically significant association was found between the incidence of stress
      fractures and t or a alleles. Decreased T-scores were also associated with the
      presence of f and B alleles. Mean values of T-scores of SI were statistically
      significantly lower in patients than in controls (p=0.018). These results suggest
      that the FokI and BsmI polymorphisms of the VDR gene could be associated with
      increased risk of stress fractures among military personnel. Moreover, a low
      calcaneal SI could represent a measurable index of this increased risk.

PMID- 19391079
TI  - Zygomycosis in neonates: an uncommon but life-threatening infection.
AB  - We systematically reviewed all published cases of zygomycosis, an increasingly
      important infection with high mortality, in neonates. We searched PubMed and
      individual references for English publications of single cases or case series of
      neonatal (0 to 1 month) zygomycosis. Cases were included if they fulfilled
      prespecified criteria. Fifty-nine cases were published through July 2007. Most of
      the infants (77%) were premature. The most common sites of zygomycosis were
      gastrointestinal (54%) and cutaneous (36%) diseases. This pattern differs from
      sinopulmonary and rhinocerebral patterns of older children. Fifty-six percent of
      cases were diagnosed by histology only and 44% by histology and culture. RHIZOPUS
      spp. were isolated from 18/25 (72%) cases. Thirty-seven percent of patients
      received no antifungal therapy. Thirty-two (54%) neonates underwent surgery with
      (39%) or without (15%) antifungal agents. Overall mortality was 64%. A higher
      fraction of neonates treated with amphotericin B and surgery survived than those
      who received no therapy (70% versus 5%). Zygomycosis is a life-threatening
      infection in neonates with a distinct pattern of gastrointestinal and cutaneous
      involvement and high mortality. Combination of amphotericin B and surgery was
      common management strategy in survivors.

PMID- 19391081
TI  - Pregnancy complicated by triploidy: a comparison of the three karyotypes.
AB  - We evaluated triploid pregnancy to determine whether there are clinically
      important differences between the three karyotypes: 69,XXX, 69,XXY, and 69,XYY.
      Prospectively maintained cytogenetic databases at five tertiary care centers were
      retrospectively reviewed over a 10-year period to identify all triploid
      pregnancies. Targeted ultrasounds were reviewed to identify fetal and placental
      findings. Sonographic findings were compared by karyotype. There was a total of
      549 triploid gestations; preimplantation genetic diagnosis (PGD) detected 413
      triploid embryos, and the cytogenetic databases provided 136 clinical pregnancies
      with triploidy. In triploid embryos with PGD, the frequency of the 69,XYY
      karyotype was 8.7% (36/413), compared with 0.74% (1/136) during the first
      trimester of clinical pregnancies (p = 0.002). In clinical pregnancies, 60%
      (36/60) of 69,XXY fetuses survived the first trimester of development compared
      with 69% (52/75) of 69,XXX fetuses (p = NS). No clinically important differences
      were observed between 69,XXX and 69,XXY karyotypes in terms of type, number, or
      severity of fetal or placental anomalies. Gestations with a 69,XYY karyotype are
      found less frequently compared with gestations with a 69,XXX or 69,XXY karyotype.
      The decline in fetal survival of the 69,XYY triploid karyotype needs further
      investigation. There are significant abnormalities detected during prenatal
      sonography in most all clinically recognized cases of triploidy. Sonography
      cannot reliably distinguish between the 69,XXY and 69,XXX karyotypes.

PMID- 19391080
TI  - Neonatal cord blood subsets and cytokine response to bacterial antigens.
AB  - We compared lymphocyte subsets and cytokine responses to bacteria among term,
      preterm infants, and adults. Lymphocyte subset percentages in cord blood (22
      preterm, 27 term neonates) and peripheral blood from 21 adults and
      cytokine/chemokine interleukin (IL)-6, IL-8, IL-10, IL-12, interferon gamma (IFN
      gamma) responses to Escherichia coli, group B Streptococcus (GBS), Staphylococcus
      epidermidis, and Lactobacillus plantarum (Lp299v) were assessed by flow
      cytometry. Preterm compared with term infants had increased CD8 (+) T cells (p =
      0.02) and reduced naive CD4 (+) T cells (p < 0.0001). Memory T and natural killer
      (NK) T cells were reduced (p < 0.001) in neonates; NK and CD56 (+)161 (+) NK
      cells were increased (p < 0.001). CD56 (+)CD8 (+) NK cells were higher in preterm
      compared with term infants. Despite individual exceptions, cytokine responses in
      neonates were weaker than adults except for IL-8 response to E. coli in preterm
      and IL-12 response to Lp299v in term infants. IL-10 responses were weaker in
      preterm (p = 0.01) and term (p = 0.005) infants to S. epidermidis and to E. coli
      (p = 0.03 for both) compared with adults. Differences in regulatory
      subpopulations of NK and T cells between neonates and adults and term compared
      with preterm infants were observed. These differences rather than intrinsic
      functional deficiency may account for neonatal cytokine responses to bacteria.

PMID- 19391083
TI  - Placental laser surgery for severe previable feto-fetal transfusion syndrome in
      triplet gestation.
AB  - Information on feto-fetal transfusion syndrome (FFTS) in higher-order multifetal
      gestation is limited. We report outcomes of 10 triplet pregnancies treated by
      fetoscopic laser occlusion of the chorioangiopagous vessels (FLOC). The study
      period was August 1992 to August 2008. Inclusion criteria were gestational age <
      or =25 weeks and ultrasound confirmation of monochorionicity in at least one twin
      set and FFTS. Treatment included FLOC, exit amnioreduction, and cerclage when
      indicated. Hospital records, placental pathology, neonatal course, and long term
      follow-up of the mother and infants were reviewed. There were eight triamnionic
      dichorionic and two triamnionic monochorionic triplets. Mean maternal age was
      29.8 years, and five conceived following in vitro fertilization. FFTS stage at
      treatment was > or =II in all cases, at a mean gestational age 20.9 +/- 2.2
      weeks. Two patients required immediate rescue cerclage, and all 10 had
      hypoproteinemia and anemia. Mean age at delivery was 31.2 +/- 3.4 weeks, with a
      mean birth weight 1568.4 +/- 498 g for the live-born fetuses. Twenty-three (77%)
      fetuses survived, with at least one fetus surviving in 9 (90%) cases. Cerebral
      ultrasound imaging and neurological examination were normal in all neonates, and
      clinical follow-up has remained normal at 67.5 +/- 56 months for the group. FLOC
      is feasible in dichorionic and monochorionic triplet pregnancy complicated by
      FFTS. Outcomes are comparable to our experience with twins, namely improved
      perinatal survival and neonatal morbidity when compared with alternative
      treatments.

PMID- 19391082
TI  - The risk of congenital malformations and other neonatal and maternal health
      outcomes among licensed cosmetologists.
AB  - This study sought to determine if cosmetologists in New York State (NYS) have a
      higher risk of complications of labor/delivery or congenital malformations and
      poor neonatal health indicators among their offspring compared with Realtors and
      the general population. This retrospective cohort study matched licensing records
      for cosmetologists and realtors to birth records and the NYS Congenital
      Malformations Registry from 1997 to 2003. A random sample of NYS birth
      certificates, frequency matched to cosmetologists on year of child's birth,
      mother's ethnicity, and education, was also formed. Outcomes include
      malformations of each major organ system, neonatal health indicators, and
      complications of labor/delivery. Multivariate logistic regression was used to
      calculate odds ratios (ORs) and 95% confidence intervals (CIs), controlling for
      potential confounders. Compared with Realtors, cosmetologists had an increased
      risk of several maternal and neonatal health indicators, including postpartum
      hemorrhage (OR = 2.12; 95% CI 1.26, 3.58), failure to progress (OR = 1.31; 95% CI
      1.12, 1.54), and newborn intubation (OR = 2.34; 95% CI 1.21, 4.51), among others.
      We did not observe an increased risk of congenital malformations among
      cosmetologists' offspring. Working as a cosmetologist was positively associated
      with several adverse maternal perinatal and neonatal health indicators but was
      not associated with congenital malformations in this study. These results are
      useful for hypothesis generating.

PMID- 19391084
TI  - Cerebral arteriovenous shunts regression in two preterm newborns with heart
      failure in utero.
AB  - In this report, the cases of two newborn infants with cerebral arteriovenous
      shunts and heart failure in utero are presented. Different from the malformations
      of the vein of Galen, which usually generate a progressive and lethal heart
      failure after birth, our cases show heart failure resolution after birth,
      together with cerebral vascular shunt disappearance. Therefore, we hypothesized
      that the opening of arteriovenous shunts was a secondary modification due to the
      intrauterine heart failure. From our cases, it appears that, despite the dramatic
      echographic appearance, generalized cerebral venous dilatation can resolve
      spontaneously without sequelae.

PMID- 19391085
TI  - Full publication of clinical trials presented at a national maternal-fetal
      medicine meeting: is there a publication bias?
AB  - We sought to determine the rate and timing of full publication of clinical trials
      initially presented as abstracts at a national maternal-fetal medicine (MFM)
      research meeting and identify factors associated with publication status. All
      abstracts presented over a 3-year period (2000 to 2002) at the Society of MFM
      Annual Meeting were reviewed. Abstracts reporting outcomes for prospective,
      interventional research studies with human subjects were included. Multiple
      electronic databases were searched for evidence of full publication with a
      minimum of 5-year follow-up. The reporting characteristics of abstracts that were
      published as full research reports were compared with those not published. During
      the study period, 2012 abstracts were presented and 90 met all study criteria
      (4.5%). Of these, 55.6% (n = 50) were subsequently published as full research
      reports. There were no differences in the use of placebo, randomization, or
      blinding. Studies reaching full publication had larger sample size (median 174
      [12 to 4165] versus 96 [22 to 1039]; p = 0.02) and were more likely to report
      treatment differences (60% versus 32.5% p = 0.009). After adjusting for
      confounding factors, the reporting of treatment differences remained associated
      with full publication (odds ratio 3.3 [95% confidence interval 1.3 to 8.0]; p =
      0.01). Full publication of clinical trials occurred more often if treatment
      differences were present. Positive publication bias exists in MFM research.

PMID- 19391086
TI  - The role of complement in neurodevelopmental impairment following neonatal
      hypoxic-ischemic encephalopathy.
AB  - Evidence has accumulated implicating complement activation in the pathogenesis of
      acute post-hypoxic-ischemic cerebral injury in infants who develop hypoxic
      ischemic encephalopathy (HIE). However, the relationship between complement
      activation and subsequent neurological impairment is not known. We tested the
      hypothesis that in human neonates, post-hypoxic-ischemic complement activation
      within the central nervous system is positively associated with the acquisition
      of subsequent neurodevelopmental abnormalities. This prospective study included
      18 full-term infants diagnosed with HIE following resuscitation at birth and
      seven control infants. Cerebrospinal fluid (CSF) samples were obtained from all
      infants in the first 24 hours of life as part of routine investigations to
      exclude sepsis and meningitis. Concentrations of terminal complement complexes
      (TCC), complement component 9 (C9), and albumin were quantified by enzyme-linked
      immunosorbent assay in all CSF samples. Neurological examination and Denver
      Developmental Screening Test II were performed at 6 and 12 months of life. Of the
      18 HIE subjects, nine died, six survived with significant neurological
      impairment, and three had normal neurological outcomes. In the CSF of the 15 HIE
      infants who died or survived with abnormal outcomes, the mean concentration of
      TCC was increased compared with controls (p = 0.026) and the mean C9
      concentration appeared to be decreased but the difference was not statistically
      significant (p = 0.056). Similar to the TCC concentration, the concentration of
      albumin in the CSF was significantly increased in infants with abnormal outcomes
      (p = 0.005). This study indicates that complement activation following
      resuscitation at birth, as manifested by increased TCC in the CNS, is positively
      correlated with the combination of the development of subsequent neurological
      sequelae and death. Further study incorporating larger sample sizes will be
      required to confirm this association. This step is essential before clinical
      trials of complement inhibitors can be justified in human neonates who suffer
      birth asphyxia.

PMID- 19391088
TI  - Preexpanded radial forearm free flap for one-stage total penile reconstruction in
      female-to-male transsexuals.

PMID- 19391087
TI  - [Suicidal behaviour of elderly psychiatric inpatients--prevalence and risk
      factors].
AB  - OBJECTIVE: The study aimed at evaluating prevalence and risk factors of suicidal
      behaviour of elderly psychiatric inpatients based on the German psychiatric basic
      documentation system (DGPPN-BADO). METHODS: A total of 5,356 elderly psychiatric
      inpatients (> 65 years) with 7,658 episodes of inpatient care in a psychiatric
      university hospital between 1996 and 2006 was included in the study. Besides
      descriptive analyses, univariate analyses and binary logistic regression analyses
      were performed. RESULTS: Four inpatient suicides and 14 attempted suicides of
      twelve inpatients were recorded during the 11-year period. Three of the 4
      inpatient suicides and 6 of the 12 inpatients attempting suicide during hospital
      stay had a diagnosis of depression. Furthermore, 280 suicides before admission
      were attempted by 262 patients. Regression analysis revealed life time suicide
      attempt, ICD-10 diagnosis F43, period of onset of present episode less than one
      week and ICD-10 diagnosis F32 / F33 as significant predictors of attempted
      suicide before admission. Suicidal thoughts without concomitant suicide attempt
      before admission were recorded for 389 admissions of 346 patients. According to
      regression analysis, risk of suicidal thoughts before admission is increased for
      patients with life time suicide attempt, ICD-10 diagnosis F43, ICD-10 diagnosis
      F32 / F33, ICD-10 diagnosis F30 / F31, greater number of hospital admissions,
      short cumulative length of stay and non-chronic course of disease. CONCLUSIONS:
      Examination of risk faktors of suicidal behaviour within the framework of
      hospital admissions should not be restricted exclusively to period of hospital
      stay. Relevant risk factors can be found even before hospital stay and could be a
      cue for suicide prevention already in the forefront of admission.

PMID- 19391089
TI  - Superficial temporal recipient vessels in microvascular orbit and scalp
      reconstruction of oncologic defects.
AB  - The superficial temporal artery and vein (STA/V) are often considered suboptimal
      recipient vessels due to anecdotal reports that they are unreliable and prone to
      spasm. This is unfortunate, as their position greatly facilitates reconstruction
      of the scalp and orbit. We present our experience with 28 patients who underwent
      microvascular craniofacial reconstruction of oncological defects using the STA/V
      as recipients over a 4-year period at a single institution. Rates of vessel
      thrombosis, total flap loss, and partial flap loss were not significantly
      different from 282 flaps anastomosed to neck vessels. With knowledge of the
      anatomy and proper technique, the STA/V are reliable and available in most
      patients and can facilitate microvascular orbit and scalp reconstruction. The
      proximity they offer allows more flexibility in flap pedicle length requirement
      and avoids the use of vein grafts. Caution should be exercised if there is a
      history of radiation therapy.

PMID- 19391090
TI  - Attributes and shortcomings of acoustic Doppler sonography in identifying
      perforators for flaps from the lower extremity.
AB  - The preoperative identification of perforators can facilitate the appropriate
      design of perforator flaps from the lower extremity. Although computed
      tomographic arteriography can now be considered the gold standard in this regard,
      this technology is not universally available or inexpensive, with a nonnegligible
      risk from radiation exposure. An old standby, the ubiquitous acoustic Doppler
      sonography, still has a role as an alternative, despite perhaps its too high
      sensitivity and low specificity. Regardless of the modality employed, the
      efficacious harvest of a perforator flap will still require constant vigilance
      during its dissection due to anatomic anomalies of the course of these
      perforators, which is the expected norm.

PMID- 19391091
TI  - The lower-extremity Allen test.
AB  - The Allen test is used to diagnose the relative contribution of the ulnar and
      radial arteries to each hand. We modified this test to investigate the relative
      vascular contributions to distal perfusion of the lower extremity. With the
      patient supine, a handheld Doppler is used to locate the first dorsal metatarsal
      artery. The posterior tibial artery (PT) and dorsalis pedis artery (DP) pulses
      are compressed. A persistent signal indicates collateral flow through the
      peroneal artery (PA). Sequential decompression is then used to evaluate the
      relative contribution of the PT and DP to distal circulation. We report a case in
      which angiography failed to predict reliance on the PT. In this case, performance
      of the lower-extremity Allen test (LEAT) led to an alternative recipient vessel
      choice. The LEAT is simple to perform and provides a valuable adjunct to
      angiographic data.

PMID- 19391097
TI  - Interactions between mitogen-activated protein kinase and protein kinase C
      signaling during oocyte maturation and fertilization in a marine worm.
AB  - In the marine nemertean worm Cerebratulus, follicle-free oocytes re-initiate
      meiosis and undergo nuclear disassembly (=germinal vesicle breakdown, GVBD) after
      being stimulated to mature by seawater (SW) or cAMP-elevating drugs. Previously,
      it has been shown that inhibitors of mitogen-activated protein kinase (MAPK) or
      protein kinase C (PKC) signaling can reduce SW-induced GVBD in nemertean oocytes
      without affecting cAMP-induced GVBD. Thus, SW and cAMP elevators may trigger
      alternative pathways that vary in their dependence on MAPK and PKC. To further
      characterize such signaling cascades, immunoblotting analyses of MAPK and PKC
      activities were conducted on oocytes treated with U0126, an inhibitor of the MAPK
      kinase (MAPKK) that is responsible for activating MAPK. Based on these analyses
      and comparisons with the MAPKK inhibitor CI1040 that inactivates MAPK without
      preventing GVBD, U0126 seems to block GVBD via a non-MAPK-mediated effect that
      involves PKC. Moreover, evidence is presented for post-GVBD oocytes establishing
      positive feedback between MAPK and PKC signaling. Such feedback apparently allows
      the activities of both kinases to be maintained before insemination and to
      undergo concomitant downregulation after fertilization. Furthermore, in oocytes
      treated with MAPKK and PKC inhibitors during fertilization, sperm incorporation
      and polar body formation still occur, but normal cleavage is prevented. This
      suggests that although GVBD and aspects of post-fertilization activation may
      proceed in the absence of MAPK or PKC, such kinases are apparently required for
      proper embryogenesis. Collectively, these results are discussed relative to
      previous analyses of the interactions and functions of MAPK and PKC signaling
      during oocyte maturation and fertilization.

PMID- 19391098
TI  - Radical cations of amino acids and peptides: structures and stabilities.
AB  - Amino acid and peptide radical cations, M*+, are formed by oxidative
      dissociations of [Cu(auxiliary ligand)(M)]*2+ and [Metal(III)(salen)(M)]+
      complexes. The most easily formed radicals contain either an aromatic or basic
      amino acid residue. Aromatic amino acids have low ionization energies, are easily
      oxidized and delocalize the charge and spin over the ring systems; basic amino
      acids facilitate formation of alpha-radicals that have captodative structures in
      which the charge and spin are formally separated, although feeding back some of
      the charge onto the amide or carboxyl group adjacent to the radical center
      through hydrogen bonding enriches the electron-withdrawing properties and is
      highly stabilizing. DFT calculations located five isomers of His*+ with an alpha
      radical with a captodative structure at the global minimum in a deep potential
      well. An IRMPD spectrum confirmed that this isomer is the experimentally observed
      "long-lived" isomer. When both charge and spin are on the peptide backbone, as in
      [GGG]*+, captodative structures have the lowest energies; the barriers to
      interconversion between the three isomeric alpha-radicals of [GGG]*+ are high as
      the charge impedes migration of a hydrogen atom. Dissociation of [GGG]*+ is
      charge-driven. In peptide radical cations containing a basic amino acid residue
      the charge is sequestered on the side chain and the radical center, either on the
      backbone or on another side chain, initiates the fragmentation.

PMID- 19391099
TI  - The ion funnel: theory, implementations, and applications.
AB  - The electrodynamic ion funnel has enabled the manipulation and focusing of ions
      in a pressure regime (0.1-30 Torr) that has challenged traditional approaches,
      and provided the basis for much greater mass spectrometer ion transmission
      efficiencies. The initial ion funnel implementations aimed to efficiently capture
      ions in the expanding gas jet of an electrospray ionization interface and
      radially focus them for efficient transfer through a conductance limiting
      orifice. We review the improvements in fundamental understanding of ion motion in
      ion funnels, the evolution in its implementations that have brought the ion
      funnel to its current state of refinement, as well as applications of the ion
      funnel for purposes such as ion trapping, ion cooling, low pressure electrospray,
      and ion mobility spectrometry.

PMID- 19391100
TI  - Catalytic isoforms Tpk1 and Tpk2 of Candida albicans PKA have non-redundant roles
      in stress response and glycogen storage.
AB  - Candida albicans cAMP-dependent protein kinase (PKA) is coded by two catalytic
      subunits (TPK1 and TPK2) and one regulatory subunit (BCY1). In this organism the
      cAMP/PKA signalling pathway mediates basic cellular processes, such as the yeast
      to-hyphae transition and cell cycle regulation. In the present study, we
      investigated the role of C. albicans PKA in response to saline, heat and
      oxidative stresses as well as in glycogen storage. To fine-tune the analysis, we
      performed the studies on several C. albicans PKA mutants having heterozygous or
      homozygous deletions of TPK1 and/or TPK2 in a different BCY1 genetic background.
      We observed that tpk1Delta/tpk1Delta strains developed a lower tolerance to
      saline exposure, heat shock and oxidative stress, while wild-type and
      tpk2Delta/tpk2Delta mutants were resistant to these stresses, indicating that
      both isoforms play different roles in the stress response pathway. We also found
      that regardless of the TPK background, heterozygous and homozygous BCY1 mutants
      were highly sensitive to heat treatment. Surprisingly, we observed that those
      strains devoid of one or both TPK1 alleles were defective in glycogen storage,
      while strains lacking Tpk2 accumulated higher levels of the polysaccharide,
      indicating that Tpk1 and Tpk2 have opposite roles in carbohydrate metabolism.

PMID- 19391101
TI  - Retraction. Cardioprotective effects of hydroxysafflor yellow A on diabetic
      cardiac insufficiency attributed to up-regulation of the expression of
      intracellular calcium handling proteins of sarcoplasmic reticulum in rats.

PMID- 19391102
TI  - Jurors' perceptions of juvenile defendants: the influence of intellectual
      disability, abuse history, and confession evidence.
AB  - Understanding jurors' perceptions of juvenile defendants has become increasingly
      important as more and more juvenile cases are being tried in adult criminal court
      rather than family or juvenile court. Intellectual disability and child
      maltreatment are overrepresented among juvenile delinquents, and juveniles
      (particularly disabled juveniles) are at heightened risk for falsely confessing
      to crimes. In two mock trial experiments, we examined the effects of disability,
      abuse history, and confession evidence on jurors' perceptions of a juvenile
      defendant across several different crime scenarios. Abused juveniles were treated
      more leniently than nonabused juveniles only when the juvenile's crime was
      motivated by self-defense against the abuser. Jurors used disability as a
      mitigating factor, making more lenient judgments for a disabled than a
      nondisabled juvenile. Jurors also completely discounted a coerced confession for
      a disabled juvenile, but not for a nondisabled juvenile. In fact, compared with
      when it was portrayed as voluntary, jurors generally discounted a juvenile's
      coerced confession. Implications for public policy and directions for future
      research are discussed.

PMID- 19391103
TI  - Concepts in in vivo siRNA delivery for cancer therapy.
AB  - In vivo gene silencing using RNAi plays an important role in target validation
      and is advancing towards the development of RNAi-based therapeutics. RNAs were
      thought to have just two broad functions in cells as messenger RNAs (mRNAs) and
      ribosomal RNAs, but recently the relevance of microRNAs is becoming more clearly
      understood. mRNA molecules transmit information between DNA and protein and, as
      such, are vital intermediaries for gene expression. Ribosomal and transfer RNAs
      have structural, catalytic, and information-decoding roles in the process of
      protein synthesis, whereas microRNAs are regulators of gene expression. This
      review presents the early and intriguing successes of using siRNAs for in vivo
      gene silencing and its use as a possible cancer therapeutics.

PMID- 19391104
TI  - Kauren-19-oic acid induces DNA damage followed by apoptosis in human leukemia
      cells.
AB  - This study evaluated the potential cytotoxicity of the natural diterpenoids
      kauren-19-oic acid (KA), 14-hydroxy-kaurane (1) and xylopic acid (2), and semi
      synthetic derivatives of KA (3-5) towards human cancer cell lines (K562, HL60,
      MDA-MB435 and SF295) and lymphocytes. Mouse erythrocytes were used to verify a
      possible hemolytic activity Cytotoxicity mechanisms were investigated in HL60
      cells. KA showed a moderate antiproliferative effect in MTT assay towards all
      cancer cells (IC(50), 9.1-14.3 microg ml(-1)). However, KA appeared not selective
      to cancer cells, since it also inhibited the lymphocytes proliferation (IC(50),
      12.6 microg ml(-1)). Unlike KA, compounds 1-5 displayed no cytotoxicity and were
      also free from antiproliferative and hemolytic effects, suggesting that the
      exocyclic double bond (C16) unit may be the active pharmacophore of KA
      cytotoxicity. KA-treated HL60 cells displayed decreased proliferation (5-bromo
      2';-deoxyuridine incorporation assay) and topoisomerase I activity (DNA
      relaxation assay). These assays revealed that KA primarily intercalates with DNA
      and not with topoisomerase I. Fluorescence microscopy using AO/EB (acridine
      orange/ethidium bromide) staining indicated that KA can induce both apoptosis and
      necrosis in HL-60 cell cultures, which corroborate the findings with MTT. From
      these findings, we conclude that KA, although demonstrating cytotoxic potential,
      may have a limited or poor therapeutic potential due to lack of selectivity to
      tumor cells. Further studies on the structure modification of KA and the
      mechanism of the new derivatives are currently in progress.

PMID- 19391105
TI  - Effect of salicylic acid and diclofenac on the medium-chain and long-chain acyl
      CoA formation in the liver and brain of mouse.
AB  - Medium-chain and long-chain acyl-CoA esters are key metabolites in fatty acid
      metabolism. Effects of salicylic acid on the in vivo formation of acyl-CoAs in
      mouse liver and brain were investigated. Further, inhibition of the medium-chain
      and long-chain acyl-CoA synthetases by salicylic acid and diclofenac was
      determined in mouse liver and brain mitochondria. Acyl-CoA esters were analyzed
      by liquid chromatography-tandem mass spectrometry. The amounts of medium-chain
      acyl-CoAs (C(6), C(8) and C(10)) were less than long-chain acyl-CoAs (C(16:0),
      C(18:0), C(18:1) and C(20:4)) in both liver and brain. The administration of
      salicylic acid decreased the levels of both the medium-chain (C(6), C(8) and
      C(10)) and long-chain acyl-CoAs (C(16:0), C(18:0), C(18:1) and C(20:4)) in liver.
      In brain, however, only long-chain acyl-CoAs were decreased. The level of
      salicylyl-CoA detected in brain was about 12% of that in liver. Salicylic acid
      had a strong inhibitory activity (IC(50) = 0.1 mm) for the liver mitochondrial
      formation of hexanoyl-CoA from hexanoic acid, whereas diclofenac was weak (IC(50)
      = 4.4 mm). In contrast, diclofenac (IC(50) = 1.4 mm) inhibited the liver
      mitochondrial long-chain acyl-CoA synthetases more potently than salicylic acid
      (IC(50) = 25.5 mm). Similar inhibitory activities for the acyl-CoA synthetases
      were obtained in the case of the brain and liver mitochondria, except for the
      weak inhibition of brain medium-chain acyl-CoA synthetases by salicylic acid
      (IC(50) = 1.8 mm). These findings suggest that salicylic acid and diclofenac
      exhibit different mechanisms of inhibition of fatty acid metabolism depending on
      the length of the acyl chain and tissues, and they may contribute to the further
      understanding of the toxic effects associated with these drugs.

PMID- 19391106
TI  - Chromosomal mobilization and reintegration of Sleeping Beauty and PiggyBac
      transposons.
AB  - The Sleeping Beauty and PiggyBac DNA transposon systems have recently been
      developed as tools for insertional mutagenesis. We have compared the chromosomal
      mobilization efficiency and insertion site preference of the two transposons
      mobilized from the same donor site in mouse embryonic stem (ES) cells under
      conditions in which there were no selective constraints on the transposons'
      insertion sites. Compared with Sleeping Beauty, PiggyBac exhibits higher
      transposition efficiencies, no evidence for local hopping and a significant bias
      toward reintegration in intragenic regions, which demonstrate its utility for
      insertional mutagenesis. Although Sleeping Beauty had no detectable genomic bias
      with respect to insertions in genes or intergenic regions, both Sleeping Beauty
      and PiggyBac transposons displayed preferential integration into actively
      transcribed loci.

PMID- 19391107
TI  - Mechanism of growth inhibition by MicroRNA 145: the role of the IGF-I receptor
      signaling pathway.
AB  - MicroRNA 145 (miR145) has been proposed as a tumor suppressor. It was previously
      shown that miR145 targets the 3' UTR of the insulin receptor substrate-1 (IRS-1)
      and dramatically inhibits the growth of colon cancer cells. miR145 also targets
      the type 1 insulin-like growth factor receptor (IGF-IR). We show here that an IRS
      1 lacking its 3' UTR is no longer down-regulated by miR145 and rescues colon
      cancer cells from miR145-induced inhibition of growth. An IGF-IR resistant to
      miR145 (again by elimination of its 3' UTR) is not down-regulated by miR145 but
      fails to rescue colon cancer cells from growth inhibition. These and other
      results, taken together, indicate that down-regulation of IRS-1 plays a
      significant role in the tumor suppressor activity of miR145.

PMID- 19391109
TI  - Extracellular matrix controls insulin signaling in mammary epithelial cells
      through the RhoA/Rok pathway.
AB  - Cellular responses are determined by a number of signaling cues in the local
      microenvironment, such as growth factors and extracellular matrix (ECM). In
      cultures of mammary epithelial cells (MECs), functional differentiation requires
      at least two types of signal, lactogenic hormones (i.e., prolactin, insulin, and
      hydrocortisone) and the specialized ECM, basement membrane (BM). Our previous
      work has shown that ECM affects insulin signaling in mammary cells. Cell adhesion
      to BM promotes insulin-stimulated tyrosine phosphorylation of insulin receptor
      substrate-1 (IRS-1) and association of PI3K with IRS-1, whereas cells cultured on
      stromal ECM are inefficient in transducing these post-receptor events. Here we
      examine the mechanisms underlying ECM control of IRS phosphorylation. Compared to
      cells cultured on BM, cells on plastic exhibit higher level of RhoA activity. The
      amount and the activity of Rho kinase (Rok) associated with IRS-1 are greater in
      these cells, leading to serine phosphorylation of IRS-1. Expression of dominant
      negative RhoA and the application of Rok inhibitor Y27632 in cells cultured on
      plastic augment tyrosine phosphorylation of IRS-1. Conversely, expression of
      constitutively active RhoA in cells cultured on BM impedes insulin signaling.
      These data indicate that RhoA/Rok is involved in substratum-mediated regulation
      of insulin signaling in MECs, and under the conditions where proper adhesion to
      BM is missing, such as after wounding and during mammary gland involution,
      insulin-mediated cellular differentiation and survival would be defective.

PMID- 19391110
TI  - Differential developmental toxicities of di-n-hexyl phthalate and dicyclohexyl
      phthalate administered orally to rats.
AB  - The objective of this study was to evaluate the developmental toxic potential of
      di-n-hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant
      Sprague-Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250,
      500 and 750 mg kg(-1) per day, by gavage, on gestational days (GD) 6-20. Maternal
      food consumption and body weight gain were significantly reduced at 750 mg kg(-1)
      per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight
      associated with peroxisomal enzyme induction were seen in dams treated with DnHP
      or DCHP. DnHP caused dose-related developmental toxic effects, including marked
      embryo mortality at 750 mg kg(-1) per day, and presence of malformations (mainly
      cleft palate, eye defects and axial skeleton abnormalities) and significant
      decreases in fetal weight at 500 and 750 mg kg(-1) per day. Significant delay of
      ossification and increase in the incidence of skeletal variants (e.g.
      supernumerary lumbar ribs) also appeared at 250 mg kg(-1) per day. DCHP produced
      fetal growth retardation at 750 mg kg(-1) per day, as evidenced by significant
      reduction of fetal weight. DnHP and DCHP induced a significant and dose-related
      decrease in the anogenital distance of male fetuses at all doses, and there was a
      significant increase in the incidence of male fetuses with undescended testis at
      500 and 750 mg kg(-1) per day of DnHP. In conclusion, DnHP showed clear
      embryolethality and teratogenicity, but not DCHP. There was evidence that both
      phthalates could alter the development of the male reproductive system after in
      utero exposure, DnHP being much more potent than DCHP.

PMID- 19391111
TI  - S-allylcysteine attenuates renal injury by altering the expressions of iNOS and
      matrix metallo proteinase-2 during cyclosporine-induced nephrotoxicity in Wistar
      rats.
AB  - Cyclosporine A (CsA) is the first choice immunosuppressant used for the
      prevention of allograft rejection in solid organ transplantation and immune
      mediated diseases. Reactive oxygen species-induced oxidative stress and lipid
      peroxidation are implicated in the pathophysiology of CsA-induced renal injury.
      In this work, we have studied the effect of a garlic-derived compound, S
      allylcysteine (SAC) on CsA-induced nephrotoxicity. CsA-induced nephrotoxicity was
      assessed in terms of increased activities of serum marker enzymes and levels of
      kidney markers. CsA administration induced significant elevation in lipid
      peroxidation along with abnormal levels of enzymic and non-enzymic antioxidants
      in the kidneys of the rats. SAC administration improved renal function by
      bringing about a significant decrease in peroxidative levels and increase in
      antioxidant status. Elevated expressions of inducible nitric oxide synthase
      (iNOS) and nuclear factor kappa B (NF-kappaB) due to CsA administration were
      reduced by SAC treatment. An increase in the expression of matrix
      metalloproteinase-2 (MMP-2) was evident in CsA-induced groups of rats, which was
      moderately reduced in SAC treated rats. An increase in the levels of serum
      constituent's urea, uric acid and creatinine was observed in the CsA-induced
      rats, which was reduced upon treatment with SAC. These results indicate that SAC
      has a protective action against CsA-induced nephrotoxicity which is also
      supported by histopathological studies. A comparative study of the antioxidant
      vitamin C and SAC is more valuable to assess the efficacy of the drug that can be
      used for the treatment of nephrotoxicity.

PMID- 19391112
TI  - Variable expression of Dkc1 mutations in mice.
AB  - In humans mutations in DKC1, cause the rare bone marrow failure syndrome
      dyskeratosis congenita. We have used gene targeting to produce mouse ES cells
      with Dkc1 mutations that cause DC when in humans. The mutation A353V, the most
      common human mutation, causes typical DC to very severe DC in humans. Male
      chimeric mice carrying this mutation do not pass the mutated allele to their
      offspring. The mutation G402E accounts for a single typical case of DC in a human
      family. The allele carrying this mutation was transmitted to the offspring with
      high efficiency. Expression of RNA and protein was reduced compared to wild type
      animals, but no abnormalities of growth and development or in blood values were
      found in mutant mice. Thus Dkc1 mutations have variable expression in mice, as in
      humans.

PMID- 19391113
TI  - An essential gene mutagenesis screen across the highly conserved piebald deletion
      region of mouse chromosome 14.
AB  - The piebald deletion complex is a set of overlapping chromosomal deficiencies on
      distal mouse chromosome 14. We surveyed the functional genetic content of the
      piebald deletion region in an essential gene mutagenesis screen of 952 genomes to
      recover seven lethal mutants. The ENU-induced mutations were mapped to define
      genetic intervals using the piebald deletion panel. Lethal mutations included
      loci required for establishment of the left-right embryonic axis and a loss-of
      function allele of Phr1 resulting in respiratory distress at birth. A functional
      map of the piebald region integrates experimental genetic data from the deletion
      panel, mutagenesis screen, and the targeted disruption of specific genes. A
      comparison of several genomic intervals targeted in regional mutagenesis screens
      suggests that the piebald region is characterized by a low gene density and high
      essential gene density with a distinct genomic content and organization that
      supports complex regulatory interactions and promotes evolutionary stability.

PMID- 19391114
TI  - Bmp2 and Bmp4 genetically interact to support multiple aspects of mouse
      development including functional heart development.
AB  - Bone morphogenetic proteins (BMPs) have multiple roles during embryogenesis.
      Current data indicate that the dosage of BMPs is tightly regulated for normal
      development in mice. Since Bmp2 or Bmp4 homozygous mutant mice show early
      embryonic lethality, we generated compound heterozygous mice for Bmp2 and Bmp4 to
      explore the impact of lowered dosage of these BMP ligands. Genotyping pups bred
      between Bmp2 and Bmp4 heterozygous mice revealed that the ratio of adult compound
      heterozygous mice for Bmp2 and Bmp4 is much lower than expected. During
      embryogenesis, the compound heterozygous embryos showed several abnormalities,
      including defects in eye formation, body wall closure defects, and ventricular
      septal defects (VSD) in the heart. However, the ratio of the compound
      heterozygous embryos was the same as expected. Caesarean sections at E18.5
      revealed that half of the compound heterozygotes died soon after birth, and the
      majority of the dead individuals exhibited VSD. Survivors were able to grow to
      adults, but their body weight was significantly lower than control littermates.
      They demonstrated progressive abnormalities in the heart, eventually showing a
      branched leaflet in atrioventricular valves. These results suggest that the
      dosage of both BMP2 and 4 is critical for functional heart formation during
      embryogenesis and after birth.

PMID- 19391115
TI  - Stable generation of serum- and feeder-free embryonic stem cell-derived mice with
      full germline-competency by using a GSK3 specific inhibitor.
AB  - C57BL/6 (B6)-derived embryonic stem (ES) cells are not widely used to generate
      knockout mice despite the advantage of a well-defined genetic background because
      of poor developmental potential. We newly established serum- and feeder-free B6
      ES cells with full developmental potential by using leukemia inhibitory factor
      (LIF) and 6-bromoindirubin-3'-oxime (BIO), a glycogen synthase kinase-3 (GSK3)
      inhibitor. BIO treatment significantly increased the expression levels of 364
      genes including pluripotency markers such as Nanog and Klf family. Unexpectedly,
      by aggregating or microinjecting those ES cells to each eight-cell-stage diploid
      embryo, we stably generated germline-competent ES-derived mice. Furthermore,
      founder mice completely derived from female XO, heterozygous, or homozygous
      mutant B6 ES cells were directly available for intercross breeding and phenotypic
      analysis. We hereby propose that serum- and feeder-free B6 ES cells stimulated
      with LIF plus GSK3 inhibitor are valuable for generating mouse models on B6
      background.

PMID- 19391117
TI  - Tissue selective expression of conditionally-regulated ROCK by gene targeting to
      a defined locus.
AB  - ROCK kinases regulate actin-myosin structures downstream of Rho GTPases. We
      generated mice expressing 4-hydroxytamoxifen (4HT)-regulated human ROCK II
      (ROCKII:mER) under the transcriptional control of the cytokeratin14 (K14)
      promoter. The K14-ROCKII:mER minigene was recombineered into a novel cloning
      vector containing the promoter and first exon of the human HPRT gene, and second
      and third exons of the mouse Hprt gene. Homologous recombination into the Hprt
      locus, which is deleted for the promoter and first two exons in HM1 embryonic
      stem cells, reconstitutes a functional Hprt gene, allowing for growth in HAT
      (hypoxanthine-aminopterin-thymidine) medium. K14-promoter-driven ROCKII:mER
      expression was restricted to a superficial cell layer in embryoid bodies, with
      increased ROCK substrate phosphorylation induced by 4HT. ROCKII:mER-expressing
      primary murine keratinocytes responded to 4HT with increased substrate
      phosphorylation and cytoskeleton rearrangements, indicating that ROCKII:mER
      activity is regulated by 4HT in the target tissue. K14-ROCKII:mER mice will be
      valuable for examining the role of ROCK in skin development and cancer.

PMID- 19391118
TI  - Magic spot: (p) ppGpp.
AB  - Guanosine 5'-(tri)diphosphate, 3'-diphosphate [(p) ppGpp] is a small nucleic acid
      that helps bacteria survive in limited environments. Gene chip shows that (p)
      ppGpp is a global transcription-regulator of genes related to important bacterial
      metabolic processes. Therefore, more attention should be focused on the molecular
      mechanisms of (p) ppGpp, as it is the foundation to understanding how bacteria
      adapt to extreme circumstances through the stringent response.

PMID- 19391119
TI  - Both DNA damage and mitochondrial dysfunction are involved in novel
      oxadiazolo[3,4-d]pyrimidine nucleoside derivatives-induced cancer cell death.
AB  - Eight novel oxdiazolo[3,4-d]pyrimidine nucleoside derivatives (I-VIII) were
      synthesized to investigate their anti-tumor effects and possible mechanisms. Four
      human cancer cell lines including Hela, ECA109, HepG2 and A459 cells were used.
      Compounds VI and VIII showed significant inhibition on cancer cell proliferation
      by MTT assay and IC50 values were around 30-70 micromol l(-1). Both compounds
      could release nitric oxide (NO), led to a significant intracellular free Ca2+
      overloading and resulted in mitochondrial dysfunction, showing a decrease in
      mitochondrial membrane potential in HepG2 cells in a dose-dependent manner.
      Furthermore, compound VIII induced obvious DNA damage on HepG2 cells. These data
      indicate that compounds VI and VIII are two active antitumor compounds, and both
      DNA damage and mitochondrial dysfunction are involved in the mechanisms
      underlying oxadiazolo[3,4-d]pyrimidine nucleoside derivative-induced cancer cell
      death, which might also be related to the released NO.

PMID- 19391120
TI  - Immunohistochemical studies on early stage of hepatic damage induced by subacute
      inhalation of toluene vapor in rats.
AB  - Toluene is one of the most widely used organic solvents and is commonly
      recognized as a noxious substance inducing chronically toxic damage to neural,
      hepatic and renal functions in the workers engaged in printing and painting.
      Although hepatic cells are generally considered to be vulnerable and susceptible
      to various organic solvents, particularly chloroform and other halogenated
      hydrocarbons, the hepatotoxic effects of aromatic hydrocarbons including toluene
      have not yet been sufficiently characterized. In particular, it still seems
      unclear whether toluene itself can directly act on hepatic cells, inducing toxic
      damage to their metabolism and function. To assess the toxic effect of toluene
      inhalation on rat liver, immunohistochemical analyses of the histological markers
      for hepatic damage were carried out in animals exposed subacutely to toluene
      vapor. The immunoreactivities of heat shock proteins (HSP-70 and HSP-90) and
      cytochrome P4502E1 (CYP2E1) in the liver were analyzed to assess the hepatotoxic
      damage induced by toluene inhalation, and the expression of these histological
      markers was shown to be substantially enhanced by the subacute exposure to
      toluene vapor. Toluene inhalation was furthermore shown to enhance the
      immunoreactivities of alpha-smooth muscle actin (alpha-SMA), collagen,
      glucocorticoid receptors (GR) and leptin receptors (Ob-R) in the liver.
      Additional studies using human hepatoma HepG2 cells showed that toluene can
      directly induce toxic damage to cells. These findings suggest that toluene
      inhalation may primarily induce hepatic damage, which may be secondarily
      exacerbated by the activation of systemic processes possibly connected with
      glucocorticoids and leptin.

PMID- 19391121
TI  - G protein signaling controls the differentiation of multiple cell lineages.
AB  - G protein-coupled receptors (GPCRs) detect a great diversity of extracellular
      stimuli ranging from hormonal peptides, chemokines, neurotransmitters, lipids,
      nucleotides, amino acids, biogenic amines to ions. G protein-coupled pathways
      regulate a rich collection of biological processes involved in normal
      physiological function of the body as well as in pathological progression of
      diseases. In addition to their function in postmitotic steady-state tissues,
      GPCRs have been implicated in the differentiation of stem cells and tissue
      specific progenitor cells during development. Examples of these include the
      functions of nucleotides and neuropeptides in neuronal differentiation and axon
      growth, chemokines in lymphocyte differentiation and activation, and other GPCR
      mediated processes in the differentiation of adipocytes, osteoblasts and smooth
      muscle cells. This review summarizes the recent advances in our understanding of
      the importance of GPCR-linked signaling cascades in the differentiation of
      different cell lineages.

PMID- 19391122
TI  - Omega-3 polyunsaturated fatty acids and human health outcomes.
AB  - Current intakes of very long chain omega-3 fatty acids, eicosapentaenoic acid
      (EPA), and docosahexaenoic acid (DHA) are low in most individuals living in
      Western countries. A good natural source of these fatty acids is seafood,
      especially oily fish. Fish oil capsules contain these fatty acids too. Very long
      chain omega-3 fatty acids are readily incorporated from capsules into transport,
      functional, and storage pools. This incorporation is dose-dependent and follows a
      kinetic pattern that is characteristic for each pool. At sufficient levels of
      incorporation, EPA and DHA influence the physical nature of cell membranes and
      membrane protein-mediated responses, eicosanoid generation, cell signaling and
      gene expression in many different cell types. Through these mechanisms, EPA and
      DHA influence cell and tissue physiology, and the way cells and tissues respond
      to external signals. In most cases, the effects seen are compatible with
      improvements in disease biomarker profiles or in health-related outcomes. As a
      result, very long chain omega-3 fatty acids play a role in achieving optimal
      health and in protection against disease. Long chain omega-3 fatty acids protect
      against cardiovascular morbidity and mortality, and might be beneficial in
      rheumatoid arthritis, inflammatory bowel diseases, childhood learning, and
      behavior, and adult psychiatric and neurodegenerative illnesses. DHA has an
      important structural role in the eye and brain, and its supply early in life is
      known to be of vital importance. On the basis of the recognized health
      improvements brought about by long chain omega-3 fatty acids, recommendations
      have been made to increase their intake.

PMID- 19391123
TI  - DeltaNp63 isoforms differentially regulate gene expression in squamous cell
      carcinoma: identification of Cox-2 as a novel p63 target.
AB  - The p53 homologue p63 produces six different isoforms that are important in
      development of epithelial tissues and squamous cell carcinoma of the head and
      neck (SCCHN). In SCCHN, the expression of p63 isoforms is highly complex, with
      over-expression of DeltaNp63 and p63beta isoforms in many tumours. To date,
      little is known about the functions of different DeltaNp63 isoforms and
      elucidating the distinctive properties of DeltaNp63 isoforms will help to clarify
      how they influence tumour biology. By gene expression profiling of SCCHN cells
      over-expressing the DeltaNp63 isoforms we identified different effects of the
      three isoforms, with DeltaNp63beta being more effective at gene induction than
      DeltaNp63alpha and DeltaNp63gamma, whereas DeltaNp63gamma was most effective at
      repressing gene expression. Thus, tumours expressing even low levels of
      DeltaNp63beta or DeltaNp63gamma may have distinct clinicopathological
      characteristics important for metastasis and therapeutic response. Induction of
      cyclooxygenase-2 (Cox-2) was shown by each isoform and data were confirmed by
      independent quantitative RT-PCR and western blotting. No direct binding of
      DeltaNp63 to the Cox-2 promoter could be seen, neither could any evidence for Cox
      2 induction as a consequence of activated NF-kappaB pathway responses be found.
      As Cox-2 is known to inhibit radiotherapy responses in SCCHN patients, data
      indicate an additional mechanism through which DeltaNp63 acts to promote cell
      survival and influence therapeutic response of SCCHN. MIAME-compliant data have
      been deposited in the MIAME Express database (Accession No. E-MEXP-1842).

PMID- 19391124
TI  - Retraction. Cardioprotective effects of the combined use of puerarin and
      danshensu on acute ischemic myocardial injury in rats.

PMID- 19391125
TI  - Retraction. The correlation between angiogenesis and abnormal expression of
      SERCA2a, phospholamban and the endothelin pathway in heart failure, and
      improvement by puerarin.

PMID- 19391126
TI  - Retraction. Comparison of the therapeutic effects of different compositions of
      muskone in the treatment of experimental myocardial infarct in rats and analgesia
      in mice.

PMID- 19391127
TI  - Leptin and endothelin-1 mediated increased extracellular matrix protein
      production and cardiomyocyte hypertrophy in diabetic heart disease.
AB  - BACKGROUND: We investigated the role of leptin and its interaction with
      endothelin 1 (ET-1) in fibronectin (FN) synthesis and cardiomyocyte hypertrophy,
      two characteristic features of diabetic cardiomyopathy. METHODS: Endothelial
      cells [human umbilical vein endothelial cells (HUVECs)] were examined for FN
      production and neonatal rat cardiomyocytes for hypertrophy, following incubation
      with glucose, ET-1, leptin and specific blockers. FN, ET-1, leptin and leptin
      receptors mRNA expression and FN protein were measured. Myocytes were also
      morphometrically examined. Furthermore, hearts from streptozotocin-diabetic rats
      were analysed. RESULTS: Glucose caused increased FN mRNA and protein expression
      in HUVECs and cardiomyocytes hypertrophy along with upregulation of ET-1 mRNA,
      leptin mRNA and protein. Glucosemimetic effects were seen with leptin and ET-1.
      Leptin receptor antagonist (leptin quadruple mutant) and dual endothelin A
      endothelin B (ETA/ETB) receptor blocker bosentan normalized such abnormalities.
      Hearts from the diabetic animals showed hypertrophy and similar mRNA changes.
      CONCLUSION: These data indicate that in diabetes increased FN production and
      cardiomyocyte hypertrophy may be mediated through leptin with its interaction
      with ET-1.

PMID- 19391128
TI  - Molecular characterization of post-transplant lymphoproliferative disorders of
      donor origin occurring in liver transplant recipients.
AB  - Post-transplant lymphoproliferative disorders (PTLDs) represent a frequent
      complication of solid organ transplantation. Although most PTLDs arise from
      recipient lymphoid cells, a considerable fraction of cases may arise from donor B
      cells. In an attempt to clarify the histogenesis and pathogenesis of PTLDs
      derived from donor B-cells, monoclonal PTLDs occurring in liver transplant
      recipients were chosen as a model to compare donor (D-PTLDs) versus recipient
      PTLDs (R-PTLDs). The tumour panel included nine D-PTLDs and six R-PTLDs. D-PTLDs
      were early-onset, EBV-infected lymphoproliferations classified as polymorphic
      PTLD (P-PTLD; n = 7) or diffuse large B-cell lymphoma (DLBCL; n = 2) with tumour
      localization confined to the hepatic hilum. All R-PTLDs were late-onset DLBCLs
      and showed extrahepatic localization. A BCL-6(-)/MUM1(+)/CD138(+/-) phenotype,
      consistent with a post-germinal centre (GC) stage of pre-terminal B-cell
      differentiation, was observed in all D-PTLDs and in 2/6 R-PTLDs, whereas a
      BCL6(+)/MUM1(-)/CD138(-) profile, reminiscent of GC B-cells, was detected in 4/6
      R-PTLDs. The presence of somatic IGHV hypermutation was observed in 6/9 D-PTLDs
      and in 4/6 R-PTLDs, suggesting derivation from antigen-experienced B-cells. IGHV4
      39 was the IGHV gene most frequently encountered, being rearranged in 3/9 D
      PTLDs. Among IGHV-mutated PTLDs, a mutational profile suggesting antigen
      stimulation and/or selection was observed in 4/6 D-s and in 2/4 R-PTLDs. The
      presence of ongoing IGHV mutations was detected in 2/4 D-PTLDs. Aberrant SHM was
      detected in 10/15 (66.7%) PTLDs, including 6/9 D-PTLDs and 4/6 R-PTLDs. Our
      findings suggest that (i) D-PTLDs show a clinical presentation distinct from R
      PTLDs; (ii) immunophenotypic and genetic features of D-PTLDs are consistent with
      mature, GC-experienced B-cells; (iii) transformed donor-derived B-cells may
      experience antigen-driven stimulation and selection, and may acquire genetic
      lesions during neoplastic expansion in the recipient environment; and (iv) EBV
      infection and expression of viral oncoproteins may be relevant in the
      pathogenesis of D-PTLDs.

PMID- 19391129
TI  - COX-2 is induced by HGF stimulation in Met-positive thyroid papillary carcinoma
      cells and is involved in tumour invasiveness.
AB  - Thyroid papillary carcinoma (TPC) cells express high levels of cytoplasmic cyclo
      oxygenase 2 protein. Analysis of microdissected samples of the tumour and of the
      paired normal thyroid tissue confirmed that mRNA transcripts for cyclo-oxygenase
      2 (COX-2) were significantly more numerous in the tumour (7.6 +/- 13-fold; p =
      0.01). High levels of COX-2 mRNA were not associated with age, sex, tumour size
      or lymph node metastasis. COX-2 was not homogeneously expressed throughout the
      tumour, but was significantly higher at the tumour invasion front. Hepatocyte
      growth factor (HGF) can up-regulate the expression of COX-2 mRNA. A marked
      increase in COX-2 mRNA levels was observed in 8/8 primary TPC cultures after HGF
      stimulation (6.3 +/- 6-fold) and in two papillary carcinoma cell lines (TPC-1 and
      NPA). Specific involvement of the high-affinity HGF receptor (Met protein) was
      suggested by the observation that PHA-665752, an inhibitor of the catalytic
      activity of c-Met kinase, caused a 54% reduction of the hepatocyte growth factor
      induced COX-2 up-regulation. The possibility that HGF-Met interactions also had a
      causative role in the up-regulation of COX-2 in vivo was investigated in 30
      tumour samples, where it was found that there was a statistically significant
      correlation (p = 0.001, r = 0.85) in the levels of expression of MET and COX-2
      RNAs. The biological role of COX-2 in TPC cells was investigated by treating the
      TPC cell lines with the specific COX-2 inhibitor NS-398. It was found that NS-398
      treatment significantly reduced the migration (50-75%) and invasiveness (47-92%)
      of tumour cells, but did not alter cell proliferation. Our data suggest that the
      increased expression of Met protein in TPC cells has a role in up-regulating the
      expression of COX-2, which in turn contributes to the invasive capacity of TPC
      cells.

PMID- 19391130
TI  - Dasatinib induces complete cytogenetic response and loss of F359C in an imatinib
      resistant chronic myelocytic leukemia patient.

PMID- 19391131
TI  - Reliability of leukostasis grading score to identify patients with high-risk
      hyperleukocytosis.

PMID- 19391132
TI  - Gene signatures of pulmonary metastases of renal cell carcinoma reflect the
      disease-free interval and the number of metastases per patient.
AB  - Our understanding of metastatic spread is limited and molecular mechanisms
      causing particular characteristics of metastasis are largely unknown. Herein,
      transcriptome-wide expression profiles of a unique cohort of 20 laser-resected
      pulmonary metastases (Mets) of 18 patients with clear-cell renal cell carcinoma
      (RCC) were analyzed to identify expression patterns associated with two important
      prognostic factors in RCC: the disease-free interval (DFI) after nephrectomy and
      the number of Mets per patient. Differentially expressed genes were identified by
      comparing early (DFI < or = 9 months) and late (DFI > or = 5 years) Mets, and
      Mets derived from patients with few (< or =8) and multiple (> or =16) Mets. Early
      and late Mets could be separated by the expression of genes involved in
      metastasis-associated processes, such as angiogenesis, cell migration and
      adhesion (e.g., PECAM1, KDR). Samples from patients with multiple Mets showed an
      elevated expression of genes associated with cell division and cell cycle (e.g.,
      PBK, BIRC5, PTTG1) which indicates that a high number of Mets might result from
      an increased growth potential. Minimal sets of genes for the prediction of the
      DFI and the number of Mets per patient were identified. Microarray results were
      confirmed by quantitative PCR by including nine further pulmonary Mets of RCC. In
      summary, we showed that subgroups of Mets are distinguishable based on their
      expression profiles, which reflect the DFI and the number of Mets of a patient.
      To what extent the identified molecular factors contribute to the development of
      these characteristics of metastatic spread needs to be analyzed in further
      studies.

PMID- 19391133
TI  - RNAi targeting urokinase-type plasminogen activator receptor inhibits metastasis
      and progression of oral squamous cell carcinoma in vivo.
AB  - It has been admitted that urokinase-type plasminogen activator receptor (u-PAR)
      is overexpressed in many human malignant tumors including oral squamous cell
      carcinoma (OSCC) and plays an important role in a variety of cancer key cellular
      events as a versatile signaling orchestrator. In our study, a retroviral vector
      expressing u-PAR-specific siRNA was injected into OSCC xenografts of nude mice to
      observe its inhibitory effects on OSCC. Our data demonstrate that siRNA targeting
      u-PAR markedly suppressed tumor growth, reduced the expression of proliferation
      related gene, Ki-67 and increased cell apoptosis, accompanying with the efficient
      and specific inhibition of endogenous u-PAR expression in OSCC. More importantly,
      the mRNA and protein expression of MMP-2, MMP-9, VEGF-C, VEGF-D and VEGFR-3 that
      are intimately involved in oral cancer invasion and metastasis, was
      simultaneously downregulated significantly as determined by quantitative real
      time RT-PCR, Western blot and immunohistochemistry; and Gelatin and fibrin
      zymography showed that MMP-9, MMP-2 and u-PA enzymatic activities were
      significantly reduced in u-PAR-specific siRNA group, compared to those in control
      groups. In addition, the expression of MDR-1 gene related to drug resistance was
      obviously inhibited by silencing of u-PAR. These findings suggest that RNAi
      targeting u-PAR could effectively inhibit the metastasis and progression of OSCC
      in vivo. Thus, it may be used as a potent and specific therapy for oral cancer,
      especially in inhibiting and preventing cancer cell invasion and metastasis.

PMID- 19391134
TI  - Season of diagnosis has no effect on survival from malignant melanoma.
AB  - Diagnosis in summer had been shown to be associated with better survival from
      some cancers, but such studies on malignant melanoma where sun exposure is a risk
      factor for disease are rare. We evaluated seasonality in melanoma diagnosis and
      its effect on survival in Victoria, Australia using 26,060 cases reported to the
      population-based Victorian Cancer Registry during 1986-2004. To estimate the
      amplitude of the seasonal variation, we calculated the ratio of the number of
      melanoma cases diagnosed in summer to that in winter. Linear regression was
      undertaken to assess the variation in thickness, the main prognostic indicator
      for melanoma, by season of diagnosis adjusting for sex, anatomical site, year of
      diagnosis and age at diagnosis. We modeled excess mortality using Poisson
      regression controlling for possible confounders in order to study the effect of
      season of diagnosis on survival. An overall 46% summer diagnostic excess was
      evident (summer-to-winter ratio 1.46; 95% CI 1.41, 1.52). Results of linear
      regression showed that melanoma diagnosed in winter were thicker than those
      diagnosed in any other season (percentage difference in thickness -2.01, -6.97
      and -10.68 for spring, summer and autumn, respectively; p < 0.001). In the
      Poisson regression model of relative survival, cases diagnosed in spring, summer
      or autumn had slightly lower excess mortality than those diagnosed in winter
      before adjustment for other variables, but after adjustment the excess mortality
      ratios were close to unity. Our findings do not support the hypothesis that
      melanoma cases diagnosed in winter have worse prognosis than cases diagnosed in
      other seasons.

PMID- 19391135
TI  - Estrogen regulation of thrombospondin-1 in human breast cancer cells.
AB  - Expression of thrombospondin-1 (TSP-1), a large extracellular matrix protein, has
      been associated with modulation of angiogenesis and tumor growth. Both pro and
      antiangiogenic properties of TSP-1 have been described, and the role of TSP-1
      expression in the growth and progression of human breast cancer is not clear.
      Because estrogens cause progression of many breast cancers, and estradiol (E2)
      downregulates a TSP-1 receptor, we examined whether TSP-1 is regulated by
      estrogen and involved in tumor progression. E2 induced TSP-1 expression in T47-D
      and MCF-7 breast cancer cells in vitro within 3 to 6 hr; the induction was
      blocked by the anti-estrogen ICI 182,780, indicating that estrogen receptors (ER)
      are necessary for this effect. Furthermore, E2 caused the production of TSP-1
      protein from tumor cells in an ER-alpha-dependent manner. The E2-mediated TSP-1
      RNA induction was dose-dependent and blocked by actinomycin D, indicating that
      the response to E2 was at least partly transcriptional. Transfection studies with
      deletion constructs of the TSP-1 promoter identified an estrogen-responsive
      region in the human TSP-1 promoter, located between -2,200 and -1,792 bp upstream
      of the transcription start site. An antibody against TSP-1 restricted the
      proliferation of E2-dependent MCF-7 cells in vitro and in vivo. A panel of breast
      cancer cells proliferated in the presence of low concentrations of exogenous TSP
      1, whereas higher concentrations inhibited proliferation. A real-time PCR
      analysis showed that E2 also induced TSP-1 mRNA in the normal mammary glands of
      immature ovariectomized mice in an ER-dependent manner. In summary, we report the
      novel observation that TSP-1 production is directly controlled by estrogens in ER
      positive breast cancer cells, and the released protein has pro-growth regulatory
      functions. Consequently, we propose that TSP-1 could be a therapeutic target for
      anti-tumor therapy in early-stage tumors. (c) 2009 UICC.

PMID- 19391136
TI  - Gender-specific activity of chemotherapy correlates with outcomes in
      chemosensitive cancers of young adulthood.
AB  - Good evidence indicates that adolescents and young adults (AYAs) with cancer do
      badly compared with children with similar cancers. The reasons are poorly
      understood. Australian registry data on 14,824 cancers of adolescence and young
      adulthood seen between 1982 and 2002 were reviewed. A detailed substudy of
      clinical characteristics was analyzed from 179 AYAs with Hodgkin lymphoma (HL),
      Ewing sarcoma (ES) or osteosarcomas (OS) treated at a single institution. Despite
      significant improvements in survival for both groups over the period in question,
      for acute lymphoblastic leukaemia, rhabdomyosarcoma, ES, OS and HL, survival for
      AYAs was worse than for children. For ES, OS and HL, the survival gap occurred
      almost entirely in males (Hazard ratios compared with female AYAs of 1.8 [p <
      0.01], 1.4 [p = 0.03] and 1.5 [p < 0.01] respectively). Survival outcomes from
      ES, OS and HL for female AYAs were not significantly different from children of
      either sex. For brain tumors and thyroid cancers, which are primarily treated
      surgically, there were no gender-related differences in outcomes. Although no
      differences in tumor stage or compliance were identified, male AYAs experienced
      less toxicity and lower response rates to chemotherapy (p = 0.008). Young males
      account almost entirely for excess mortality from chemosensitive cancers of
      adolescence and young adulthood compared to children, which may be due to
      relative underdosing with current chemotherapy dosing algorithms.

PMID- 19391137
TI  - Functional coexpression of Interleukin (IL)-7 and its receptor (IL-7R) on Hodgkin
      and Reed-Sternberg cells: Involvement of IL-7 in tumor cell growth and
      microenvironmental interactions of Hodgkin's lymphoma.
AB  - The clinical and pathological features of classical Hodgkin lymphoma (cHL) mirror
      an abnormal tissue and systemic immune response due to the production of a
      variety of cytokines and chemokines by the malignant Hodgkin-Reed-Sternberg (H
      RS) cells and/or surrounding reactive cells. Here, we demonstrate that HL-derived
      cell lines (L-428, KM-H2, HDLM-2, L-1236 and L-540) and primary H-RS cells from
      lymph node tissues of HL patients express the IL-7(R) receptor. IL-7 appears to
      be involved in autocrine circuitries of HL because L-1236, HDLM-2 and KM-H2 cells
      display the constitutive production of IL-7 and neutralizing anti-IL-7 antibodies
      induces a statistically significant inhibition of their basal proliferation. In
      addition, IL-7, either exogenous or fibroblasts-derived, promotes the clonogenic
      growth and reduces apoptosis of cultured H-RS cells, being also able to partially
      protect these cells from the cytotoxic effects of doxorubicin. We also provide
      evidence that IL-7 stimulates IL-6 secretion from IL-7R-expressing fibroblasts
      from HL-involved lymph nodes (HLFs), and that a striking increase in IL-6
      secretion can be observed in cocultures of HLFs with L1236 cells. Finally, we
      show that L-1236 cells-derived IL-7 represents a costimulator for proliferation
      of purified CD4+CD25+CD127(dim/-) regulatory T cells (Tregs). Taken together, our
      data indicates that the IL-7/IL-7R axis constitutes an additional signaling
      pathway between H-RS cells and their reactive cellular background, thereby
      affecting proliferation and survival of tumor cells, acting as a cofactor for
      Tregs expansion and enhancing the microenviromental production of IL-6, a
      cytokine associated with the presence of "B" symptoms and a poor outcome in HL
      patients.

PMID- 19391138
TI  - Roles of clusterin in progression, chemoresistance and metastasis of human
      ovarian cancer.
AB  - Clusterin (CLU) is a multivalent glycoprotein with ubiquitous tissue
      distribution. To address the possible differential functional roles assumed by
      different isoforms of CLU in the progression of human ovarian cancer, we
      constructed 2 human ovarian cancer cell models that represent examples of
      contradistinctive CLU expression levels. One is constitutively overexpressing
      different clusterin isoforms in SKOV3 cells by transfection of the 3 different
      expression vectors, another is silencing the intrinsically expressing clusterin
      in cisplatin-resistant human A2780-cis(CP70) tumor cells with the usage of shRNA
      mediated CLU gene silencing. Then, the different cellular localization,
      biological effects, and functional roles played in tumor progression and drug
      resistances were studied. We found that (i) in the distinct cellular contexts of
      human ovarian carcinoma SKOV3 and CP70 cells assayed, sCLU is a central molecule
      in cell homeostasis that functions as a cytoprotective protein, whereas nCLU is
      proapoptotic; (ii) In SKOV3 cells, nuclear localization of the truncated CLU is
      NLS dependent, without which the pnCLU protein was sequestrated in cytoplasm to
      prevent cytotoxicity. (iii) sCLU plays a significant role in the development of
      the chemoresistance phenotype in ovarian cancer cells. Moreover, with the CLU
      specific shRNA oligonucleotides, we successfully sensitized cells for
      chemotherapy, and inhibited cells' proliferation, migration and invasion.
      Collectively, our results reveal that, CLU gene expression might play a crucial
      role in ovarian cancer progression, adaptation and eventual resistance to
      chemotherapy through differential processing of CLU isoforms. Specifically, sCLU
      as an antiapoptotic protein, upregulated in an adaptive cell-survival manner by
      chemotherapy, confers resistance to various cell-death triggers.

PMID- 19391140
TI  - Functional molecular flasks: new properties and reactions within discrete, self
      assembled hosts.
AB  - The application of self-assembled hosts as "molecular flasks" has precipitated a
      surge of interest in the reactivity and properties of molecules within well
      defined confined spaces. The facile and modular synthesis of self-assembled hosts
      has enabled a variety of hosts of differing sizes, shapes, and properties to be
      prepared. This Review briefly highlights the various molecular flasks synthesized
      before focusing on their use as functional molecular containers--specifically for
      the encapsulation of guest molecules to either engender unusual reactions or
      unique chemical phenomena. Such self-assembled cavities now constitute a new
      phase of chemistry, which cannot be achieved in the conventional solid, liquid,
      and gas phases.

PMID- 19391146
TI  - The development of a two-leveled two cross interface for on-line coupling solid
      phase extraction and capillary electrophoresis-mass spectrometry.
AB  - A two-leveled, two cross PDMS-based interface for on-line coupling of SPE with CE
      MS was proposed. In this interface, the SPE column and the CE separation column
      were positioned orthogonally and two crosses were fabricated on the interface.
      With the two cross design, the operation of SPE could be performed independently
      without unexpected flow through leakage into the separation column. The
      performance of the interface was optimized using a peptide mixture. The position
      of the SPE column related to the CE separation channel was found to be critical
      to the performance of the system. Under the optimal position, the separation
      efficiency was similar to a CE-MS experiment without SPE. The peptide signals
      were enhanced 50- to 100-fold and the repeatability was within 4% RSD for
      migration time and 10% RSD for peak area. A tryptic digest of cytochrome c was
      used to demonstrate the feasibility of the interface in protein identification at
      a level of 1 ng/microL.

PMID- 19391145
TI  - Determination of organophosphorus pesticides by capillary electrophoresis
      inductively coupled plasma mass spectrometry with collective sample-introduction
      technique.
AB  - A new method for the determination of organophosphorus pesticides using CE-ICP-MS
      with collective sample-introduction technique has been developed in this study.
      The method has been successfully used to separate and determine dimethoate,
      trichlorfon and glyphosate with an RSD of < 5% for migration times (n = 6) and <
      4% for peak areas (n = 6). The experimental results showed that the collective
      sample-introduction considerably reduced the makeup volume and the dilution of
      analyte, and eventually resulted in a much lower detection limit and a much
      better electrophoretic resolution. The peak widths and the detection limits of
      dimethoate, trichlorfon and glyphosate obtained with this method are 15-17 s and
      0.05-0.07 microg/mL (as compound), respectively. Using this method, we have
      successfully separated and determined dimethoate, trichlorfon and glyphosate in
      vegetable sample with a recovery of 90-96%.

PMID- 19391147
TI  - Multiresidue determination of penicillins in environmental waters and chicken
      muscle samples by means of capillary electrophoresis-tandem mass spectrometry.
AB  - A new analytical method based on CZE coupled with tandem MS detection (CE-MS/MS)
      has been developed for the simultaneous determination of nine penicillins of
      human and veterinary use (nafcillin, dicloxacillin, cloxacillin, oxacillin,
      ampicillin, penicillin G, amoxicillin, penicillin V and piperacillin), whose
      levels are regulated by the EU Council regulation No. 2377/90 in animal edible
      tissues. CE separation conditions, sheath liquid composition and electrospray
      parameters have been carefully optimized to reach high sensitivity and precision.
      Separation was carried out in a 96 cm total length fused-silica capillary (50
      microm id, 360 microm od) using 60 mM ammonium acetate at pH 6.0 as running
      buffer. Lomefloxacin was used as internal standard. MS/MS experiments were
      carried out using an IT as analyzer operating in multiple reaction monitoring
      mode to achieve the minimum number of identification points established by the
      2002/657/EC European Decision. The use of an SPE procedure in two steps,
      combining Oasis hydrophilic-liphophilic balance and Alumina N cartridges provide
      a satisfactory preconcentration and clean up treatment for meat samples after
      extraction of the compounds with ACN. Only Oasis hydrophilic-liphophilic balance
      cartridges were necessary in water samples to obtain adequate recoveries. The
      method has been characterized for its use in meat and water samples, using matrix
      matched calibrations. For chicken muscle samples, LODs between 8 and 12 microg/kg
      have been obtained, in all cases lower than the maximum residue limits permitted.
      For water samples LODs from 0.18 to 0.26 microg/L could ensure its satisfactory
      application in aquatic samples.

PMID- 19391148
TI  - Development and characterization of cIEF-MALDI-TOF MS for protein analysis.
AB  - This paper describes the hyphenation of cIEF and MALDI-TOF MS via a fractionation
      or spotting device. After focusing in cIEF the compounds are hydrodynamically
      mobilized and deposited on a MALDI target plate using a sheath liquid interface,
      which provides the catholyte solution and the electrical ground. From previous
      experiments, sample conditions that resulted in a high resolution in cIEF and
      acceptable protein signal intensity in MS were selected [Silvertand et al.,
      Electrophoresis, 2008, 29, 1985-1996]. Besides the mixture of test proteins, the
      sample solution contains 1% Pharmalyte, 0.3% hydroxyethyl cellulose and 0.1%
      Tween 20 and is used for both optimization as well as characterization of the
      cIEF-MALDI-TOF MS system. Hyphenation problems encountered are mainly due to
      transfer of the liquid from the needle to the MALDI target plate and are solved
      by choosing the proper sheath catholyte (200 mM NH4OH in 50% methanol with 0.1%
      Tween20). MS electropherograms were reconstructed by plotting the intensities of
      the m/z values corresponding to the proteins versus migration time (related to
      spot number). Reproducibility, peak width and signal intensity for different
      focusing and spotting (fractionation) times were calculated using these
      reconstructed MS electropherograms as well as the UV electropherograms. The best
      results were obtained with focusing time of 75 min (no under- or overfocusing)
      and a spotting time of 5 s (highest protein signal intensity in MS). The
      applicability of the system is demonstrated by the analysis of a
      biopharmaceutical (glucagon) and its deamidation product.

PMID- 19391149
TI  - Glutamate agonists for treating schizophrenia have affinity for dopamine D2High
      and D3 receptors.
AB  - Although the glutamate agonist LY 404,039 has been used to treat schizophrenia,
      its closest congener LY 379,268 has an affinity for both glutamate and dopamine
      (DA) D2(High) receptors. Considering that all antipsychotics act on dopamine
      receptors, and considering that another laboratory reported that LY 379,268 did
      not have any affinity for the D2(High) receptor, it was necessary to examine
      whether such glutamate agonists have an affinity for D2 and D3 dopamine receptors
      in vitro. The present data show that 50-200 nM LY 379,268 inhibited the binding
      of [(3)H]domperidone and [(3)H](+)PHNO to cloned dopamine D2 receptors
      consistently and reproducibly by 16% with dissociation constants of 2.1 and 2.5
      nM at D2(High), respectively. In addition, LY 379,268 inhibited the binding of
      [(3)H]domperidone and [(3)H](+)PHNO to cloned dopamine D3 receptors with
      dissociation constants of 130 and 10 nM, respectively. LY 379,268 also inhibited
      the binding of [(3)H]domperidone to rat striata with a dissociation constant of
      22 nM, predicting a clinical antipsychotic dose of 80-100 mg/day. LY 379,268
      appears to act as an agonist at D2(High) and as an antagonist at D3, because
      guanine nucleotide eliminated the competition at D2(High) but had no effect on
      the competition at D3. The findings indicate that this type of glutamate agonist,
      LY 379,268, has a significant affinity for D2(High) and D3 receptors.

PMID- 19391150
TI  - Dopamine D2High receptors stimulated by phencyclidines, lysergic acid
      diethylamide, salvinorin A, and modafinil.
AB  - Although it is commonly stated that phencyclidine is an antagonist at ionotropic
      glutamate receptors, there has been little measure of its potency on other
      receptors in brain tissue. Although we previously reported that phencyclidine
      stimulated cloned-dopamine D2Long and D2Short receptors, others reported that
      phencyclidine did not stimulate D2 receptors in homogenates of rat brain
      striatum. This study, therefore, examined whether phencyclidine and other
      hallucinogens and psychostimulants could stimulate the incorporation of
      [(35)S]GTP-gamma-S into D2 receptors in homogenates of rat brain striatum, using
      the same conditions as previously used to study the cloned D2 receptors. Using 10
      microM dopamine to define 100% stimulation, phencyclidine elicited a maximum
      incorporation of 46% in rat striata, with a half-maximum concentration of 70 nM
      for phencyclidine, when compared with 80 nM for dopamine, 89 nM for salvinorin A
      (48 nM for D2Long), 105 nM for lysergic acid diethylamide (LSD), 120 nM for R
      modafinil, 710 nM for dizocilpine, 1030 nM for ketamine, and >10,000 nM for S
      modafinil. These compounds also inhibited the binding of the D2-selective ligand
      [(3)H]domperidone. The incorporation was inhibited by the presence of 200 microM
      guanylylimidodiphosphate and also by D2 blockade, using 10 microM S-sulpiride,
      but not by D1 blockade with 10 microM SCH23390. Hypertonic buffer containing 150
      mM NaCl inhibited the stimulation by phencyclidine, which may explain negative
      results by others. It is concluded that phencyclidine and other psychostimulants
      and hallucinogens can stimulate dopamine D2 receptors at concentrations related
      to their behavioral actions.

PMID- 19391151
TI  - Disruption of the dopamine transporter-dopamine D2 receptor interaction in
      schizophrenia.

PMID- 19391152
TI  - Visualizing vesicular dopamine dynamics in Parkinson's disease.
AB  - It has been suggested that dopamine derived from exogenous levodopa may not
      follow vesicular dynamics in Parkinson's disease (PD). Using a novel PET method
      based on the sensitivity of [(11)C]-dihydrotetrabenazine (DTBZ) binding to
      changes in vesicular dopamine levels, we show here that striatal [(11)C]-DTBZ
      binding decreases after levodopa administration in advanced PD, likely reflecting
      an increase in vesicular dopamine levels. Endogenous dopamine and exogenously
      derived dopamine seem to follow the same vesicular dynamics.

PMID- 19391153
TI  - Therapist responsiveness to child engagement: flexibility within manual-based CBT
      for anxious youth.
AB  - Therapy process research helps delineate common and specific elements essential
      to positive outcomes as well as develop best practice training protocols. Child
      involvement and therapist flexibility were rated in 63 anxious youth (ages 8-14)
      who received cognitive-behavioral therapy. Therapist flexibility, defined as
      therapist attempts to adapt treatment to a child's needs, was hypothesized to act
      as an engagement strategy that serves to increase child involvement during
      therapy. Flexibility was significantly related to increases in later child
      engagement, which subsequently predicted improvement in posttreatment diagnosis
      and impairment. Therapist flexibility was not associated with earlier measures of
      child engagement, so a mediation model could not be supported. It was also
      hypothesized that the impact of flexibility would be greatest for cases who began
      treatment highly disengaged (i.e., early involvement would moderate the effect of
      flexibility). Basic descriptive data supported this model, but formal analyses
      failed to confirm. Further descriptive analyses suggest therapists employ a range
      of adaptations and a profile of flexible applications within a manual-based
      treatment is provided. Treatment, measurement, and dissemination issues are
      discussed.

PMID- 19391155
TI  - Comments on 'Formulating the tightest bounds on causal effects in studies with
      unmeasured confounders' by M. Kuroki and Z. Cai, Statistics in Medicine 2008;
      27:6597-6611.

PMID- 19391156
TI  - Confidence intervals for the 50 per cent response dose by D. Faraggi, P. Izikson
      and B. Reiser, Statistics in Medicine 2003; 22(12):1977-1988.

PMID- 19391158
TI  - Retinal deimination in aging and disease.
AB  - Deimination is a posttranslational modification and refers to the conversion of
      protein bound arginine into citrulline. In the retina, deimination is
      predominantly catalyzed by Peptidylarginine deiminase type 2 (PAD2). PAD2
      expression and deimination are found in many different retinal layers: choroid,
      retinal pigment epithelium (RPE), photoreceptors, inner plexiform layer, inner
      nuclear layer, and retinal ganglion cell (RGC) layer. Although decreased retinal
      deimination and PAD2 expression have been found during normal aging, elevated
      PAD2 expression and deimination have been observed in age-related
      neurodegenerative diseases. The role of deimination in normal physiology and in
      late-onset and progressive ocular or retinal degenerative diseases, such as
      glaucoma and experimental autoimmune encephalomyelitis remains to be elucidated.

PMID- 19391159
TI  - Complementary and alternative medicine inclusion in physical therapist education
      in the United States.
AB  - PURPOSE: The purpose of this study was to determine the current prevalence, and
      at what level, complementary and alternative medicine (CAM) content is included
      in physical therapist (PT) education in the United States. This survey study
      provides self-report data regarding reasons why faculty members choose to include
      or not include CAM into programme content. BACKGROUND/SIGNIFICANCE: This study
      investigates the current prevalence of CAM content, and what level of inclusion
      (minimal, moderate, advanced) in PT curricula will assist programmes as they
      modify existing curricula and develop new programmes. SUBJECTS: All 196 US
      accredited programmes were included in our survey. MATERIALS AND METHODS: An IRB
      approved (Investigational Review Board), pilot-tested, two-page survey was
      emailed to all programme chairpersons of accredited PT programmes. A hard copy
      survey was mailed to non-responding programmes. ANALYSES: Returned surveys were
      analyzed descriptively to characterize the data shape, tendency and variability.
      Data were summarized in a frequency distribution and graphically depicted in a
      histogram for each category. In addition, qualitative analysis was completed for
      the explanatory data. RESULTS: Forty-seven per cent (92) of all accredited PT
      programmes (196) responded. Most commonly included CAM areas were: manipulative
      and body-based methods, alternative medical systems and biologically based
      therapies. Most frequent responses to limitations to including CAM in PT
      curriculum were: limited curriculum time, lack of evidence supporting CAM
      practices and trouble locating qualified CAM presenters. CONCLUSIONS: This survey
      suggests the following: CAM techniques are included in entry-level PT education
      in the United States; the majority of these techniques are offered at the minimum
      or exposure level; manipulative and body-based methods, alternative medical
      systems and biologically based therapies are the most frequently included CAM
      techniques.

PMID- 19391161
TI  - How I became a biochemist.

PMID- 19391160
TI  - GABA increases Ca2+ in cerebellar granule cell precursors via depolarization:
      implications for proliferation.
AB  - The amino acids glutamate and gamma-aminobutyric acid (GABA) have primarily been
      characterized as the most prevalent excitatory and inhibitory, respectively,
      neurotransmitters in the vertebrate central nervous system. However, the role of
      these signaling molecules extends far beyond the synapse. GABA, glutamate, and
      their complement of receptors are essential signaling molecules that regulate
      developmental processes in both embryonic and young adult mammals. In this
      review, we describe the current knowledge on the role of GABA and glutamate in
      development, focusing on the perinatal cerebellum. We will then present novel
      data suggesting that GABA depolarizes granule cell precursors via GABA(A)
      receptors, which leads to calcium increases in these cells. Finally, we will
      consider the role of GABA and glutamate signaling on cell proliferation and
      perhaps neural cancers. From our review of the literature and these data, we
      hypothesize that GABA(A) receptors and metabotropic glutamate receptors may be a
      novel target for the pharmacological regulation of the cerebellar tumors,
      medulloblastomas.

PMID- 19391162
TI  - Modulation of alpha-crystallin chaperone activity: a target to prevent or delay
      cataract?
AB  - Cataract, loss of eye lens transparency, is the leading cause of blindness
      worldwide. alpha-Crystallin, initially known as one of the major structural
      proteins of the eye lens, is composed of two homologous subunits alphaA- and
      alphaB-crystallins. It is convincingly established now that alpha-crystallin
      functions like a chaperone and plays a decisive role in the maintenance of eye
      lens transparency. The functional ability of alpha-crystallin subunits is to act
      in cooperation as molecular chaperones to prevent the cellular aggregation and/or
      inactivation of client proteins under variety of stress conditions. However,
      chaperone-like activity of alpha-crystallin could be deteriorated or lost during
      aging or under certain clinical conditions because of various genetic and
      environmental factors. This review will focus specifically on relevance of alpha
      crystallin chaperone function to lens transparency. In particular, we reviewed
      the studies that demonstrate the modulation of alpha-crystallin chaperone-like
      activity and discussed the possibility of chaperone-like activity of alpha
      crystallin as a potential target to prevent or delay the cataractogenesis.

PMID- 19391163
TI  - Skeletal muscle glucose uptake during exercise: a focus on reactive oxygen
      species and nitric oxide signaling.
AB  - Like insulin, muscle contraction (in vitro or in situ) and exercise increase
      glucose uptake into skeletal muscle. However, the contraction/exercise pathway of
      glucose uptake in skeletal muscle is an independent pathway to that of insulin.
      Indeed, skeletal muscle glucose uptake is normal during exercise in those who
      suffer from insulin resistance and diabetes. Thus, the pathway of contraction
      mediated glucose uptake into skeletal muscle provides an attractive potential
      target for pharmaceutical treatment and prevention of such conditions, especially
      as skeletal muscle is the major site of impaired glucose disposal in insulin
      resistance. The mechanisms regulating skeletal muscle glucose uptake during
      contraction have not been fully elucidated. Potential regulators include Ca(2+)
      (via CaMK's and/or CaMKK), AMPK, ROS, and NO signaling, with some redundancy
      likely to be evident within the system. In this review, we attempt to briefly
      synthesize current evidence regarding the potential mechanisms involved in
      regulating skeletal muscle glucose uptake during contraction, focusing on ROS and
      NO signaling. While reading this review, it will become clear that this is an
      evolving field of research and that much more work is required to elucidate the
      mechanism(s) regulating skeletal muscle glucose uptake during contraction.

PMID- 19391164
TI  - GSK-3: a key player in neurodegeneration and memory.
AB  - Abnormalities in molecular signalling have been implicated in neurodegeneration.
      It is emerging that glycogen synthase kinase-3 (GSK-3) is a key signalling
      molecule that induces neurodegeneration and deficits in memory formation related
      to Alzheimer's disease (AD). Early stages of AD are associated with deficits in
      memory formation before neuronal cell death is detectable. Recent studies in
      rodents have suggested that these impairments in memory formation might result
      from increased GSK-3 signalling, because enhanced GSK-3 activity impairs
      hippocampal memory formation. GSK-3 activity blocks synaptic long-term
      potentiation and induces long-term depression. Furthermore, increased GSK-3
      signalling is likely to be a key contributor to the formation of the pathological
      hallmarks in AD, neurofibrillary tangles (NFTs) and amyloid plaques. Recent
      studies with mouse models have indicated that GSK-3, but not cyclin-dependent
      kinase 5, is critical for hyperphosphorylation of the cytoskeletal protein tau,
      which is the prerequisite for NFT formation in AD. Furthermore, increased GSK-3
      signalling in AD mice causes abnormal processing of the amyloid precursor protein
      so that amyloid peptide production augments and neurotoxicity is induced. Taken
      together, the current evidences suggest that increased GSK-3 signalling may be
      responsible for the deficits in memory formation in early stages of AD and
      neurodegeneration in later stages of the disease.

PMID- 19391165
TI  - Oxidized proteins: mechanisms of removal and consequences of accumulation.
AB  - Elevated levels of oxidized proteins are reported in diseased tissue from age
      related pathologies such as atherosclerosis, neurodegenerative disorders, and
      cataract. Unlike the precise mechanisms that exist for the repair of nucleic
      acids, lipids, and carbohydrates, the primary pathway for the repair of oxidized
      proteins is complete catabolism to their constitutive amino acids. This process
      can be inefficient as is evidenced by their accumulation. It is generally
      considered that damaged proteins are degraded by the proteasome; however, this is
      only true for mildly oxidized proteins, because substrates must be unfolded to
      enter the narrow catalytic core. Rather, evidence suggests that moderately or
      heavily oxidized proteins are endocytosed and enter the endosomal/lysosomal
      system, indicating co-operation between the proteasomes and the lysosomes.
      Heavily modified substrates are incompletely degraded and accumulate within the
      lysosomal compartments resulting in the formation of lipofuscin-like,
      autofluorescent aggregates. Accumulation eventually results in impaired turnover
      of large organelles such as proteasomes and mitochondria, lysosomal
      destablization, leakage of proteases into the cytosol and apoptosis. In this
      review, we summarize reports published since our last assessments of the field of
      oxidized protein degradation including a role for modified proteins in the
      induction of apoptosis.

PMID- 19391166
TI  - E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.
AB  - E2F1, a member of the E2F family of transcription factors, plays a critical role
      in controlling both cell cycle progression and apoptotic cell death in response
      to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein
      is stabilized by phosphorylation and acetylation driven to its accumulation. The
      aim of the present work was to examine whether the increase in E2F1 protein
      levels observed after DNA damage is only a reflection of an increase in E2F1
      protein stability or is also the consequence of enhanced transcription of the
      E2F1 gene. The data presented here demonstrates that UV light and other
      genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner,
      which results in increasing E2F1 mRNA and protein levels. After genotoxic stress,
      transcription of cyclin E, an E2F1 target gene, was significantly induced. This
      induction was the result of two well-differentiated effects, one of them
      dependent on de novo protein synthesis and the other on the protein
      stabilization. Our results strongly support a transcriptional effect of DNA
      damaging agents on E2F1 expression. The results presented herein uncover a new
      mechanism involving E2F1 in response to genotoxic stress.

PMID- 19391168
TI  - Novel oncogenic actions of TRbeta mutants in tumorigenesis.
AB  - The thyroid hormone, T3, plays important roles in metabolism, growth, and
      differentiation. Germline mutations in thyroid hormone receptor beta (TRbeta)
      have been identified in many individuals with resistance to thyroid hormone, a
      syndrome of reduced sensitivity to T3. A close association of somatic mutations
      of TRbeta with several human cancers has become increasingly apparent, but how
      TRbeta mutants could be involved in the carcinogenesis in vivo has not been
      addressed. The creation of a mouse model (TRbeta(PV/PV) mouse) that harbors a
      knockin mutation of TRbeta (denoted TRbetaPV) has facilitated the study of the
      molecular actions of TRbeta mutants in vivo. The striking phenotype of thyroid
      cancer and the development of pituitary tumors exhibited by TRbeta(PV/PV) mice
      have uncovered novel functions of a TRbeta mutant in tumorigenesis. It led to the
      important findings that the oncogenic action of TRbetaPV is mediated by both
      genomic and nongenomic actions to alter gene expression and signaling pathways
      activity.

PMID- 19391169
TI  - Adenovirus type 5 with modified hexons induces robust transgene-specific immune
      responses in mice with pre-existing immunity against adenovirus type 5.
AB  - BACKGROUND: Adenovirus type 5 (Ad5) is widely used as a vehicle for vaccine
      delivery in the treatment of infectious disease and cancer. However, the efficacy
      of Ad5 vectors has been limited in humans because exposure to Ad5 infections
      results in most adults having neutralizing antibodies against Ad5. To overcome
      this limitation, the hexon epitope present in the fifth hypervariable region of
      Ad5 was modified. METHODS: To evaluate the ability of Ad5 vectors encoding the
      HIV env protein to induce Ag-specific immune responses in the face of pre
      existing anti-Ad5 immunity, mice were administrated intramuscularly with the Ad
      Luc vector, and then vaccinated with parental or hexon-modified Ad5 vectors (Ad
      HisHIV, Ad-END/AAAHIV or Ad-HIV) at week 8. HIV-specific cell-mediated immune
      responses were detected through a combination of tetramer assays and
      intracellular cytokine staining from weeks 8-23. RESULTS: The hexon-modified Ad
      vector was able to escape from anti-Ad5 neutralizing antibody, and mice with the
      modified vector generated significantly lower individual neutralizing antibody
      than those immunized with the parental vector. Furthermore, mice with pre
      existing anti-Ad immunity immunized with the modified vector generated
      significantly stronger cell-mediated anti-env responses than those immunized with
      the parental vector. CONCLUSIONS: These data demonstrate that Ad5 vector with
      hexon modification reduce their sensitivity to pre-existing anti-Ad immunity and
      improve their clinical utility.

PMID- 19391170
TI  - The influence of the coupling of actuation drivers of implantable hearing systems
      on the mechanics of the middle ear.
AB  - We used multifrequency tympanometry to provide middle ear mechanics after
      implantation of different implantable hearing aids. A total of 34 patients were
      included in the investigation; 19 of them were fitted with the Otologics system
      and 15 with the MED-EL Vibrant Soundbridge system. With the Otologics recipients,
      measurements were made preoperatively and both two months and at least 12 months
      postoperatively. Measurements involving the MED-EL patients were taken at least
      12 months postoperatively. For all measurements, the non-implanted contralateral
      side was used as a control. Preoperatively, the resonance frequency of the
      Otologics patients was 904.3 +/- 218.2 Hz for the implanted side and 907.1 +/-
      161.8 Hz for the non-implanted side. Postoperatively, a significant increase (p <
      0.01) compared with the preoperative value and the control side was observed
      after two months: 1111.3 +/- 234.7 Hz, as opposed to 823.8 +/- 274.5 Hz on the
      contralateral side. After 12 months, the resonance point was restored to
      approximately the preoperatively measured values: 975 +/- 55.3 Hz (implanted
      side) and 901.3 +/- 207.1 (control side). The resonance frequency in the
      Symphonix patients, as measured after at least 12 months (on average, 35 months),
      was 1006.3 +/- 269.5 Hz on the non-implanted side and 900.1 +/- 249.3 Hz on the
      implanted side. It is apparent that the resonance frequency on the implanted side
      was higher than on the control side, although the difference was not significant
      (p = 0.496). Monitoring following the implantation of active hearing systems is
      therefore recommended in order that conclusions can be drawn regarding the
      adequacy of the coupling of the actuation driver to the ossicular chain.

PMID- 19391171
TI  - Differences in psychological morbidity among Australian and Chinese caregivers of
      persons with dementia in residential care.
AB  - OBJECTIVE: The aim of the present study was to determine the effects of culture
      on caregiver psychological morbidity among informal caregivers of
      institutionalised persons with dementia in three different populations: (1)
      Shanghai, (2) Australian-Chinese and (3) Australian mainstream (non-Chinese).
      METHODS: Caregivers and residents with dementia were recruited from (1) a
      dementia hospital in Shanghai, (2) three ethno-specific Chinese nursing homes in
      Sydney and (3) four mainstream nursing homes in Sydney. Psychological morbidity
      was assessed using the Geriatric Depression Scale, mental health component (MHC)
      of the RAND-36 Health Status Inventory and a guilt scale. RESULTS: There were no
      significant differences between the three groups as measured by the guilt scale
      and MHC. Shanghai caregivers had higher mean depression scores than Australian
      Chinese caregivers (p < 0.001), who in turn had higher mean depression scores
      than Australian mainstream caregivers (p = 0.015). Higher depression scores were
      found to be inversely associated with the caregiver's education level and
      physical health status, and associated with increased frequency of nursing home
      visits, but not with levels of behavioural and psychological symptoms of dementia
      (BPSD). CONCLUSION: Levels of depression in caregivers of institutionalised
      persons with dementia differ by culture and country of residence.

PMID- 19391172
TI  - Monolithic silica capillary columns having immobilized lectins and surface bound
      polar functionalities for lectin affinity and normal phase nano-LC and CEC of
      glycoconjugates, respectively.
AB  - In this report, monolithic silica-based capillary columns were produced by the
      sol-gel process and subsequently silanized with gamma
      glycidoxypropyltrimethoxysilane to form on the surface of the monolith a reactive
      gamma-glycidoxypropylsilyl sublayer to which an interactive top layer can be
      covalently attached. The interactive top layer consisted of either an immobilized
      lectin or polar cyano functions to perform lectin affinity chromatography (LAC)
      of glycoproteins or normal phase chromatography (NPC) of glycans, respectively.
      Two lectins were immobilized, namely Con A and wheat germ agglutinin (WGA) due to
      their utility in LAC of a wide range of glycoconjugates. On the other hand, 1H
      imidazole-4,5-dicarbonitrile was covalently attached to the silica monolith to
      yield polar silica monolith referred to as 2CN-OH monolith. The two lectin
      monolithic columns were evaluated in Nano-LC with standard glycoproteins over a
      wide range of conditions and proved useful in capturing the glycoforms bearing
      the pertinent saccharidic motifs for interaction with the given lectin. The 2CN
      OH monolithic columns were effective in the profiling of glycans derived from
      glycoproteins in both NP-CEC and NP-Nano-LC with NP-CEC offering enhanced
      separation when compared to NP-Nano-LC.

PMID- 19391173
TI  - Kinetic studies of biological interactions by affinity chromatography.
AB  - The rates at which biological interactions occur can provide important
      information on the mechanism and behavior of such processes in living systems.
      This paper will discuss how affinity chromatography can be used as a tool to
      examine the kinetics of biological interactions. This approach, referred to here
      as biointeraction chromatography, uses a column with an immobilized binding agent
      to examine the association or dissociation of this agent with other compounds.
      The use of HPLC-based affinity columns in kinetic studies has received particular
      attention in recent years. Advantages of using HPLC with affinity chromatography
      for this purpose include the ability to reuse the same ligand within a column for
      a large number of experiments, and the good precision and accuracy of this
      approach. A number of techniques are available for kinetic studies through the
      use of affinity columns and biointeraction chromatography. These approaches
      include plate height measurements, peak profiling, peak fitting, split-peak
      measurements, and peak decay analysis. The general principles for each of these
      methods are discussed in this paper and some recent applications of these
      techniques are presented. The advantages and potential limitations of each
      approach are also considered.

PMID- 19391174
TI  - Exploring enantioselective molecular recognition mechanisms with chemoinformatic
      techniques.
AB  - A comprehensive review of chemoinformatic techniques and studies applied to the
      field of enantioselective molecular recognition is presented. Several approaches
      such as enantiophores/pharmacophore modelling, QSPRs, CoMFA and other insightful
      data mining procedures are discussed. The review focuses on the central role of
      chemoinformatic approaches on the establishment of connections between available
      experimental data, mainly HPLC separation data, and these algorithms that
      describe properties of chiral molecules. The general overview of the
      aforementioned calculations account for a use of these techniques as a valuable
      strategy to achieve reliable prediction systems, infer the mechanisms of chiral
      recognition, generate insight for the conception of new chiral receptors and
      corroborate and assist experimental techniques such as chiral LC. Moreover, it is
      pointed out that computer methods in this field promise a wide range of
      applications for both academia and industry, ranging from enantioselective
      reactions, drug discovery and analysis of high-throughput screenings, to
      analytical and semi-preparative separations or large-scale production of
      enantiopure compounds.

PMID- 19391175
TI  - 1H HR/MAS NMR in the suspended state: molecular recognition processes in liquid
      chromatography between steroids and a silica hydride-based cholesterol phase.
AB  - A mixture of eight steroids was separated by HPLC on a silica hydride-based
      stationary phase modified with a moiety of cholesteryl 10-undecanoate. Within the
      steroid mixture progesterone showed the longest retention time suggesting the
      strongest interaction with the stationary phase material. To obtain more detailed
      information upon the effective separation process, interaction studies were
      performed by high resolution/magic angle spinning (HR/MAS) NMR spectroscopy
      recorded in the suspended state. (1)H saturation transfer difference (STD) NMR
      experiments with T(1rho) suppression showed significant hydrophobic binding
      affinities of progesterone toward the cholesterol column material. These NMR
      results can be correlated directly to the chromatographic data obtained by HPLC.

PMID- 19391176
TI  - Comparison of enantioselective HPLC separation of structurally diverse compounds
      on chiral stationary phases with different teicoplanin coverage and distinct
      linkage chemistry.
AB  - Enantioseparation performance of two teicoplanin-based chiral stationary phases,
      Chirobiotic T and Chirobiotic T2, with different teicoplanin coverage and
      distinct linkage chemistry was compared. Three structurally diverse groups of
      analytes, amino alcohols (beta-blockers), chlorophenoxypropionic acids, and
      branched-chain amino acids, in various mobile phase compositions/separation modes
      were examined. The amino alcohols showed better enantioresolution on Chirobiotic
      T2 in reverse-phase, hydrophilic interaction chromatography, and polar-ionic mode
      separation systems. The best results with these analytes were obtained in the
      polar-ionic mobile phase. In contrast, the chlorophenoxypropionic acids and the
      branched-chain amino acids yielded an improved enantioresolution on the chiral
      stationary phase with lower amount of teicoplanin in the hydrophilic interaction
      chromatography system. The comparison of separation of the chlorophenoxypropionic
      acids enantiomers in the reverse-phase and hydrophilic interaction chromatography
      environments showed completely opposite results. While better enantioresolution
      of chlorophenoxypropionic acids was achieved on Chirobiotic T2 in mobile phases
      with low methanol content, high methanol concentration was needed to reach
      baseline enantioseparation on Chirobiotic T.

PMID- 19391177
TI  - A genome-inspired DNA ligand for the affinity capture of insulin and insulin-like
      growth factor-2.
AB  - The insulin-linked polymorphic region (ILPR) of the human insulin gene contains
      tandem repeats of similar G-rich sequences, some of which form intramolecular G
      quadruplex structures in vitro. Previous work showed affinity binding of insulin
      to an intramolecular G-quadruplex formed by ILPR variant a. Here, we report on
      interactions of insulin and the highly homologous insulin-like growth factor-2
      (IGF-2) with ILPR variants a, h, and i. Circular dichroism indicated
      intramolecular G-quadruplex formation for variants a and h. Affinity MALDI MS and
      surface plasmon resonance were used to compare protein capture and binding
      strengths. Insulin and IGF-2 exhibited high binding affinity for variants a and h
      but not i, indicating the involvement of intramolecular G-quadruplexes.
      Interaction between insulin and variant a was unique in the appearance of two
      binding interactions with K(D) approximately 10(-13) M and K(D) approximately 10(
      7) M, which was not observed for insulin with variant h (K(D) approximately 10(
      8) M) or IGF-2 with either variant (K(D)s approximately 10(-9) M). The results
      provide a basis for the design of DNA binding ligands for insulin and IGF-2 and
      support a new approach to discovery of DNA affinity binding ligands based on
      genome-inspired sequences rather than the traditional combinatorial selection
      route to aptamer discovery.

PMID- 19391178
TI  - Molecular recognition properties of tartrates and metal-tartrates in solution and
      gas phase.
AB  - Solution phase and gas phase chiral molecular recognition properties of tartrates
      (salts or esters of tartaric acid) and metal tartrates (binuclear tartrato(4-)
      metal-bridged complexes) are reviewed in conjunction with their applications in
      enantiomeric separation science and their mass spectrometric chiral
      discrimination properties.

PMID- 19391179
TI  - SwissPIT: An workflow-based platform for analyzing tandem-MS spectra using the
      Grid.
AB  - The identification and characterization of peptides from MS/MS data represents a
      critical aspect of proteomics. It has been the subject of extensive research in
      bioinformatics resulting in the generation of a fair number of identification
      software tools. Most often, only one program with a specific and unvarying set of
      parameters is selected for identifying proteins. Hence, a significant proportion
      of the experimental spectra do not match the peptide sequences in the screened
      database due to inappropriate parameters or scoring schemes. The Swiss protein
      identification toolbox (swissPIT) project provides the scientific community with
      an expandable multitool platform for automated in-depth analysis of MS data also
      able to handle data from high-throughput experiments. With swissPIT many problems
      have been solved: The missing standards for input and output formats (A),
      creation of analysis workflows (B), unified result visualization (C), and
      simplicity of the user interface (D). Currently, swissPIT supports four different
      programs implementing two different search strategies to identify MS/MS spectra.
      Conceived to handle the calculation-intensive needs of each of the programs,
      swissPIT uses the distributed resources of a Swiss-wide computer Grid
      (http://www.swing-grid.ch).

PMID- 19391180
TI  - Experimental annotation of channel catfish virus by probabilistic proteogenomic
      mapping.
AB  - Experimental identification of expressed proteins by proteomics constitutes the
      most reliable approach to identify genomic location and structure of protein
      coding genes and substantially complements computational genome annotation.
      Channel catfish herpesvirus (CCV) is a simple comparative model for understanding
      herpesvirus biology and the evolution of the Herpesviridae. The canonical CCV
      genome has 76 predicted ORF and only 12 of these have been confirmed
      experimentally. We describe a modification of a statistical method, which assigns
      significance measures, q-values, to peptide identifications based on 2-D LC ESI
      MS/MS, real-decoy database searches and SEQUEST XCorr and DeltaC(n) scores. We
      used this approach to identify CCV proteins expressed during its replication in
      cell culture, to determine protein composition of mature virions and,
      consequently, to refine the canonical CCV genome annotation. To complement
      trypsin, we used partial proteinase K digestion, which yielded greater proteome
      coverage. At FDR <5%, for peptide identifications, we identified 25/76 previously
      predicted ORF using trypsin and 31/76 using proteinase K. Furthermore, we
      identified 17 novel protein-coding regions (7 potential ATG-initiated ORF). Most
      of these novel ORF encode small proteins (<100 amino acids). Directed, strand
      specific reverse transcription real-time PCR confirmed RNA expression from 6/7
      novel ATG-initiated ORF investigated.

PMID- 19391181
TI  - Quantum dots laser desorption/ionization MS: multifunctional CdSe quantum dots as
      the matrix, concentrating probes and acceleration for microwave enzymatic
      digestion for peptide analysis and high resolution detection of proteins in a
      linear MALDI-TOF MS.
AB  - We report the first use of functionalized cadmium selinide quantum dots (CdSe
      QDs) with 11-mercaptoundecanoic acid (MUA) as the matrix for the selective
      ionization of proteins with high resolution and rapid analysis of amino acids and
      peptides by using quantum dots laser desorption/ionization mass spectrometry
      (QDLDI-MS). The mercaptocarboxylic groups of CdSe QDs have been known to be an
      effective affinity probe to interact with the biomolecules at low abundance
      level. Using these QDs as the matrix, sensitivity of the method was greatly
      enhanced and the LOQ of peptides was found to be 100 pM with RSD <10%. The QDLDI
      MS is capable for the selective ionization of insulin, lysozyme and myoglobin
      with high resolution, which is not observed with sinapic acid (SA) as the matrix.
      The QDLDI-MS technique offers many advantages for the analysis of amino acids,
      peptides and proteins with regard to simplicity, rapidity, sensitivity and the
      mass spectra were generated in the presence of signal suppressors such as urea
      and Trition X-100. In addition, the CdSe QDs have been successfully applied as
      preconcentrating probes for the analysis of digested peptides in lysozyme from
      chicken egg white by microwave-assisted enzymatic digestion. This indicates that
      the QDs are able to absorb radiation from microwave and their ability to trap
      peptides from microwave-digested lysozyme. These results demonstrate that the
      CdSe QDs are promising candidates for the selective ionization of the analytes
      with an accurate platform to the rapid screening of biomolecules.

PMID- 19391182
TI  - Comparative proteomic and regulatory network analyses of the elongating pig
      conceptus.
AB  - Embryo loss during peri-implantation can approach 20% in swine following
      artificial insemination or natural mating and coincides with rapid conceptus
      elongation. The objective of the present study was to establish a comprehensive
      profile of the abundant proteins of the pig conceptus at the time prior to
      implantation and identify stage-specific changes during elongation. The abundant
      proteins of a homogenous population of gestational day-11 ovoid (0.7-1 cm) and
      gestational day-12 filamentous (15-20 cm) porcine concepti were compared by
      extracting proteins from three independent conceptus pools and separating the
      proteins by 2-DE. Proteins in 305 spots were analyzed by MALDI-TOF or
      additionally by LC-MS/MS and 275 were positively identified representing 174
      distinct proteins. The proteins could be classified into the following functional
      categories: cell proliferation/differentiation, cytoskeleton, metabolism, and
      stress response. Based on spot density, 35 proteins associated with cell
      proliferation, differentiation, apoptosis, and embryo/maternal signaling, were
      found to be differentially expressed between ovoid and filamentous concepti. A
      comparison of the protein expression profile with transcriptomic data from pig
      concepti of the same developmental stages identified similarities and
      dissimilarities between protein and mRNA expression profiles. This proteomic
      study helps to elucidate the biological mechanisms underlying the early embryonic
      development of the pig.

PMID- 19391183
TI  - Quantitative detection of changes in the leaf-mesophyll tonoplast proteome in
      dependency of a cadmium exposure of barley (Hordeum vulgare L.) plants.
AB  - Although the vacuole is the most important final store for toxic heavy metals
      like cadmium (Cd(2+)), our knowledge on how they are transported into the vacuole
      is still insufficient. It has been suggested that Cd(2+) can be transported as
      phytochelatin-Cd(2+) by an unknown ABC transporter or in exchange with protons by
      cation/proton exchanger (CAX) transporters. To unravel the contribution of
      vacuolar transporters to Cd(2+) detoxification, a quantitative proteomics
      approach was performed. Highly purified vacuoles were isolated from barley plants
      grown under minus, low (20 microM), and high (200 microM) Cd(2+ )conditions and
      protein levels of the obtained tonoplast samples were analyzed using isobaric tag
      for relative and absolute quantitation (iTRAQ). Although 56 vacuolar transporter
      proteins were identified, only a few were differentially expressed. Under low
      Cd(2+) conditions, an inorganic pyrophosphatase and a gamma-tonoplast intrinsic
      protein (gamma-TIP) were up-regulated, indicating changes in energization and
      water fluxes. In addition, the protein ratio of a CAX1a and a natural resistance
      associated macrophage protein (NRAMP), responsible for vacuolar Fe(2+) export was
      increased. CAX1a might play a role in vacuolar Cd(2+) transport. An increase in
      NRAMP activity leads to a higher cytosolic Fe(2+) concentration, which may
      prevent the exchange of Fe(2+) by toxic Cd(2+). Additionally, an ABC transporter
      homolog to AtMRP3 showed up-regulation. Under high Cd(2+) conditions, the plant
      response was more specific. Only a protein homologous to AtMRP3 that showed
      already a response under low Cd(2+) conditions, was up-regulated. Interestingly,
      AtMRP3 is able to partially rescue a Cd(2+)-sensitive yeast mutant. The
      identified transporters are good candidates for further investigation of their
      roles in Cd(2+) detoxification.

PMID- 19391185
TI  - Stability and decline in gross motor function among children and  youth with
      cerebral palsy aged 2 to 21 years.
AB  - This paper reports the construction of gross motor development curves for
      children and youth with cerebral palsy (CP) in order to assess whether function
      is lost during adolescence. We followed children previously enrolled in a
      prospective longitudinal cohort study for an additional 4 years, as they entered
      adolescence and young adulthood. The resulting longitudinal dataset comprised
      3455 observations of 657 children with CP (369 males, 288 females), assessed up
      to 10 times, at ages ranging from 16 months to 21 years. Motor function was
      assessed using the 66-item Gross Motor Function Measure (GMFM-66). Participants
      were classified using the Gross Motor Function Classification System (GMFCS). We
      assessed the loss of function in adolescence by contrasting a model of function
      that assumes no loss with a model that allows for a peak and subsequent decline.
      We found no evidence of functional decline, on average, for children in GMFCS
      Levels I and II. However, in Levels III, IV, and V, average GMFM-66 was estimated
      to peak at ages 7 years 11 months, 6 years 11 months, and 6 years 11 months
      respectively, before declining by 4.7, 7.8, and 6.4 GMFM-66 points, in Levels
      III, IV, and V respectively, as these adolescents became young adults. We show
      that these declines are clinically significant.

PMID- 19391184
TI  - A model for intervention research in late-life depression.
AB  - OBJECTIVE: To serve as a conceptual map of the role of new interventions designed
      to reduce the burden of late-life depression. METHODS: We identified three needs
      to be addressed by intervention research: (1) the need for novel interventions
      given that the existing treatments leave many older adults depressed and
      disabled; (2) the need for procedures enabling community-based agencies to offer
      interventions of known efficacy with fidelity; and (3) the need to increase
      access of depressed older adults to care. RESULTS: Our model orders novel
      interventions according to their role in serving depressed older adults and
      according to their position in the efficacy, effectiveness, implementation, and
      dissemination testing continuum. We describe three interventions designed by our
      institute to exemplify intervention research at different level of the model. A
      common element is that each intervention personalizes care both at the level of
      the individuals served and the level of community agencies providing care. To
      this end, each intervention is designed to accommodate the strengths and
      limitations of both patients and agencies and introduces changes in the patients'
      environment and community agencies needed in order to assimilate the new
      intervention. CONCLUSIONS: We suggest that this model provides conceptual
      guidance on how to shorten the testing cycle and bring urgently needed novel
      treatments and implementation approaches to the community. While replication
      studies are important, propose that most of the support should be directed to
      those projects that take rational risks, and after adequate preliminary evidence,
      make the next step along the testing continuum.

PMID- 19391186
TI  - Abstracts of the 31st Annual Meeting of the Japan Neuroscience Society, July 9
      11, 2008.

PMID- 19391187
TI  - [Outpatient follow-up care of adult kidney transplantation patients beyond 3
      months of transplantation].

PMID- 19391188
TI  - [Abstracts of the 90th Congress of the Association of Morphologists, 5-7 June
      2008, Bordeaux, France].

PMID- 19391189
TI  - Editor's introduction.

PMID- 19391190
TI  - Higher-order BRCA1 complexity.

PMID- 19391191
TI  - MicroRNAs get a boost.

PMID- 19391192
TI  - Breaking and exiting.

PMID- 19391194
TI  - A silent inheritance.

PMID- 19391193
TI  - JMY: actin up in cell motility.

PMID- 19391195
TI  - Change of guard at the checkpoint.

PMID- 19391196
TI  - Journal club. A new ubiquitin chain, a new signal.

PMID- 19391197
TI  - GUT 2008. Abstracts of the Annual Scientific Meeting of the Malaysian Society of
      Gastroenterology and Hepatology, 21-24 August 2008.

PMID- 19391198
TI  - Structure provides clues.

PMID- 19391199
TI  - General correspondence.

PMID- 19391200
TI  - A warm thermal enclave in the late Pleistocene of the south-eastern United
      States.
AB  - Physical and biological evidence supports the probable existence of an enclave of
      relatively warm climate located between the Southern Appalachian Mountains and
      the Atlantic Ocean in the United States during the Last Glacial Maximum. The
      region supported a mosaic of forest and prairie habitats inhabited by a
      "Floridian" ice-age biota. Plant and vertebrate remains suggest an ecological
      gradient towards Cape Hatteras (35 degreesN) wherein forests tended to replace
      prairies, and browsing proboscideans tended to replace grazing proboscideans.
      Beyond 35 degreesN, warm waters of the Gulf Stream were deflected towards the
      central Atlantic, and a cold-facies biota replaced "Floridian" biota on the
      Atlantic coastal plain. Because of niche diversity and relatively benign climate,
      biodiversity may have been greater in the south-eastern thermal enclave than in
      other unglaciated areas of North America. However, the impact of terminal
      Pleistocene megafaunal extinctions may also have been shorter and more severe in
      the enclave than further north. A comparison with biotic changes that occurred in
      North America approximately 55 million years (ma) ago at the Paleocene-Eocene
      Thermal Maximum suggests that similar processes of change took place under both
      ice-house and greenhouse climates.

PMID- 19391201
TI  - Gustatory seizures and temporal lobe edema.

PMID- 19391202
TI  - Land crabs as key drivers in tropical coastal forest recruitment.
AB  - Plant populations are regulated by a diverse assortment of abiotic and biotic
      factors that influence seed dispersal and viability, and seedling establishment
      and growth at the microsite. Rarely does one animal guild exert as significant an
      influence on different plant assemblages as land crabs. We review three tropical
      coastal ecosystems-mangroves, island maritime forests, and mainland coastal
      terrestrial forests-where land crabs directly influence forest composition by
      limiting tree establishment and recruitment. Land crabs differentially prey on
      seeds, propagules and seedlings along nutrient, chemical and physical
      environmental gradients. In all of these ecosystems, but especially mangroves,
      abiotic gradients are well studied, strong and influence plant species
      distributions. However, we suggest that crab predation has primacy over many of
      these environmental factors by acting as the first limiting factor of tropical
      tree recruitment to drive the potential structural and compositional organisation
      of coastal forests. We show that the influence of crabs varies relative to tidal
      gradient, shoreline distance, canopy position, time, season, tree species and
      fruiting periodicity. Crabs also facilitate forest growth and development through
      such activities as excavation of burrows, creation of soil mounds, aeration of
      soils, removal of leaf litter into burrows and creation of carbon-rich soil
      microhabitats. For all three systems, land crabs influence the distribution,
      density and size-class structure of tree populations. Indeed, crabs are among the
      major drivers of tree recruitment in tropical coastal forest ecosystems, and
      their conservation should be included in management plans of these forests.

PMID- 19391203
TI  - An aneurysm and a primordial vessel: Two rare birds in the same tree.

PMID- 19391204
TI  - To what extent did Neanderthals and modern humans interact?
AB  - Neanderthals represent an extinct hominid lineage that existed in Europe and Asia
      for nearly 400,000 years. They thrived in these regions for much of this time,
      but declined in numbers and went extinct around 30,000 years ago. Interestingly,
      their disappearance occurred subsequent to the arrival of modern humans into
      these areas, which has prompted some to argue that Neanderthals were displaced by
      better suited and more adaptable modern humans. Still others have postulated that
      Neanderthals were assimilated into the gene pool of modern humans by admixture.
      Until relatively recently, conclusions about the relationships between
      Neanderthals and contemporary humans were based solely upon evidence left behind
      in the fossil and archaeological records. However, in the last decade, we have
      witnessed the introduction of metagenomic analyses, which have provided novel
      tools with which to study the levels of genetic interactions between this
      fascinating Homo lineage and modern humans. Were Neanderthals replaced by
      contemporary humans through dramatic extinction resulting from competition and/or
      hostility or through admixture? Were Neanderthals and modern humans two
      independent, genetically unique species or were they a single species, capable of
      producing fertile offspring? Here, we review the current anthropological,
      archaeological and genetic data, which shed some light on these questions and
      provide insight into the exact nature of the relationships between these two
      groups of humans.

PMID- 19391205
TI  - Bronchopulmonary dysplasia in a rat model induced by intra-amniotic inflammation
      and postnatal hyperoxia: morphometric aspects.
AB  - Antenatal inflammation is a known risk factor of bronchopulmonary dysplasia. The
      authors hypothesized that lipopolysaccharide (LPS) administration amplifies
      hyperoxia-induced lung injury in neonatal rats. LPS (0.5 or 1.0 microg) or normal
      saline was injected into the amniotic sacs of pregnant rats at 20 d gestation
      (term 22.5 d). After birth, rats were exposed to 85% oxygen or room air for 1 or
      2 wk. Morphometric analysis of lungs was performed on 14 d. One week of hyperoxia
      without LPS administration resulted in modest lung injury. LPS at 0.5 microg
      alone did not alter lung morphology, but amplified the effect of 1 wk of
      hyperoxia resulting in marked inhibition of alveolarization (airspaces were
      enlarged and alveolar surface areas further reduced). LPS at 1.0 microg
      independently induced modest lung injury and also amplified the effect of 1 wk of
      hyperoxia. However, this sensitizing effect of LPS was not observed in rats
      subjected to 2 wks of hyperoxia, which in itself caused extensive lung injury
      (possibly masking the effect of LPS). The authors concluded that intra-amniotic
      LPS sensitizes neonatal rat lungs, and thus, amplifies the hyperoxia-induced
      inhibition of alveolarization.

PMID- 19391206
TI  - ACP Journal Club. Students' PEARLS: successfully incorporating evidence-based
      medicine in medical students' clinical attachments.

PMID- 19391207
TI  - Gastroenterology in 2009.

PMID- 19391209
TI  - ACP Journal Club. Review: Transfer for PCI reduces 30-day mortality more than on
      site thrombolysis in STEMI.

PMID- 19391208
TI  - [Antisecretory therapy strategy for patients with bleeding and perforated
      gastroduodenal ulcers].

PMID- 19391210
TI  - [Pancreatic resections in treatment of intraductal noninvasive papillary mucinous
      tumors].

PMID- 19391211
TI  - ACP Journal Club. Review: Statins are effective for prevention of cardiovascular
      events in patients without coronary heart disease.

PMID- 19391212
TI  - MOC-31 exhibits superior reactivity compared with Ber-EP4 in invasive lobular and
      ductal carcinoma of the breast: a tissue microarray study.
AB  - Distinguishing between reactive mesothelial proliferations and adenocarcinoma is
      often very difficult. Ancillary studies, in particular immunohistochemistry, are
      often critical in detecting malignant epithelial cells, especially in serous
      effusion specimens. MOC-31 and Ber-EP4 are antibodies which target the epithelial
      cell adhesion molecule (Ep-CAM, TACSTD1) expressed in epithelial cells, and both
      are useful in distinguishing metastatic adenocarcinoma from reactive mesothelial
      cells. However, the reactivity of MOC-31 and Ber-EP4 with breast carcinoma, one
      of the more common carcinomas involving serous effusions, has not been
      extensively studied. We analyzed the immunohistochemical expression of MOC-31 and
      Ber-EP4 using tissue microarrays containing invasive ductal carcinoma (191
      cases), invasive lobular carcinoma (44 cases), and 102 other carcinoma types
      comprising primary carcinomas of lung, gynecologic tract, pancreas, colon,
      gastric, esophageal, prostate, head and neck, hepatic, and renal origin. For MOC
      31, 184 of 191 (96%) invasive ductal carcinomas and 39 of 44 (89%) invasive
      lobular carcinomas exhibited diffuse positive staining. In contrast, for Ber-EP4,
      121 of 183 (66%) invasive ductal carcinomas and 11 of 40 (27.5%) invasive lobular
      carcinomas exhibited diffuse positive staining. With the exception of 1 case of
      esophageal adenocarcinoma, all other adenocarcinomas (86 of 87 cases) exhibited
      diffuse staining with both Ber-EP4 and MOC-31. MOC-31 and Ber-EP4 exhibited
      identical staining with all other carcinoma types. Our findings indicate that MOC
      31 is superior to Ber-EP4 in detecting both invasive lobular and ductal carcinoma
      of the breast.

PMID- 19391213
TI  - [The long-term follow up review of patients with primary hyperaldosteronism after
      unilateral portalisation of adrenal and renal blood].

PMID- 19391215
TI  - ACP Journal Club. Review: Brand-name drugs are not  more effective than generic
      versions  for treating cardiovascular disease.

PMID- 19391214
TI  - [Posterior inguinal canal wall double-layer plasty for inguinal hernia].

PMID- 19391216
TI  - [A rare cause of pleural effusion].

PMID- 19391217
TI  - Calponin is expressed in serous cystadenomas of the pancreas but not in
      adenocarcinomas or endocrine tumors.
AB  - The diagnosis of serous microcystic adenoma (SMA) is usually straightforward. For
      small biopsies and/or unusual variants, the differential diagnosis includes other
      pancreatic or metastatic neoplasms showing cystic or clear cell features. We
      evaluated immunostains for potential use in the diagnosis of SMA. Cases of SMA
      were identified from archival files. Tissue cores (2 per block) were arrayed to
      create a microarray of cores measuring 2mm each. Additionally, microarrays
      previously constructed from 56 pancreatic adenocarcinomas (PACs) and 64
      pancreatic endocrine tumors (PENs) were studied. The microarrays were stained
      with calponin, chromogranin, CD10, alpha-inhibin, and monoclonal neuron-specific
      enolase (m-NSE). Subsequently, some were stained with MUC6, melan-A, D2-40, h
      caldesmon, smooth muscle actin, and smooth muscle myosin. For SMAs, staining was
      seen with calponin (85.2%), alpha-inhibin (96.2%), and m-NSE (96.2%). Focal weak
      staining was seen with MUC6 (65%). All SMAs were negative with chromogranin,
      CD10, melan-A, D2-40, h-caldesmon, smooth muscle actin, and smooth muscle myosin.
      In contrast, calponin was negative in all PACs and PENs. Staining for alpha
      inhibin was absent in PACs and present in 4.1% of PENs; whereas immunoreactivity
      for m-NSE was present in 26.8% of PACs and 73.7% of PENs. Chromogranin staining
      was present in 9.1% of PACs and 100% of PENs. An immunohistochemical profile of
      staining with calponin, alpha-inhibin, and m-NSE and absent staining with
      chromogranin supports the diagnosis of SMA, and distinguishes SMA from PAC and
      PEN. Calponin and alpha-inhibin are the most useful positive markers for SMA, and
      are negative in most entities in the differential diagnosis.

PMID- 19391218
TI  - ACP Journal Club. Self-monitored, home-based pulmonary  rehab was noninferior to
      outpatient,  hospital-based rehab for COPD.

PMID- 19391219
TI  - [Gastrointestinal fistulaes in patients with pancreanecrosis].

PMID- 19391220
TI  - Determination of EGFR status in gliomas: usefulness of immunohistochemistry and
      fluorescent in situ hybridization.
AB  - Epidermal growth factor receptor (EGFR) is produced during the molecular
      pathogenesis of glioma, and new anti-EGFR molecules are available for
      therapeutics. Consequently, analyses of the EGFR gene and protein are frequently
      used for glioma characterization. We compare the accuracy and the usefulness of 2
      currently used techniques for histologic classification of gliomas. Fluorescent
      in situ hybridization (FISH) and immunohistochemistry (IHC) techniques were used
      to assess EGFR gene amplification and protein abundance in a series of 35
      gliomas, including World Health Organization (WHO) grade I, II, and III
      astrocytomas (AI, AII, AIII), grade II and III tumors with oligodendroglial
      component (OII, OIII) and grade IV glioblastomas (GBs). EGFR gene amplification
      was found in one-third of the tumors studied. It was frequent in GB and OIII but
      was never found in AI, AII, AIII, and OII tumors. IHC and FISH provided similar
      findings for grade of tumor, despite the fact that, in contrast to the FISH gene
      amplification, EGFR protein was overexpressed in AIII and in GB. EGFR gene
      amplification was never observed in tumors not containing EGFR protein: therefore
      FISH is unnecessary when IHC shows no EGFR protein expression. EGFR gene
      amplification seems to be restricted to high-grade tumors, WHO grade IV
      astrocytomas, and grade III oligodendroglial tumors.

PMID- 19391221
TI  - ACP Journal Club. Review: Metformin reduces risk for CV mortality compared with
      other oral diabetes drugs or placebo in type 2 diabetes.

PMID- 19391222
TI  - [Protocols of Moscow surgical society 2611 th and 2613 th sessions].

PMID- 19391223
TI  - ACP Journal Club. Review: Oral drugs for gestational diabetes  do not increase
      adverse maternal and  neonatal outcomes more than insulin.

PMID- 19391224
TI  - ACP Journal Club. Review: Early surgery improves outcomes  in patients with
      primary supratentorial  intracerebral hemorrhage.

PMID- 19391225
TI  - ACP Journal Club. Review: Interferon and nucleoside/tide  analogues reduce risk
      for hepatocellular  cancer in patients with chronic hepatitis B.

PMID- 19391226
TI  - ACP Journal Club. Supplementation with vitamin E or vitamin C  did not differ
      from placebo for major  cardiovascular events and mortality.

PMID- 19391227
TI  - ACP Journal Club. Review: Long-term annual conversion rate  to dementia was 3.3%
      in older adults with  mild cognitive impairment.

PMID- 19391229
TI  - ACP Journal Club. Review: Newer screening tests have varied  sensitivity and
      moderate-to-high specificity  for detecting colorectal cancer.

PMID- 19391228
TI  - ACP Journal Club. Review: Individual alarm features have  moderate-to-high
      specificity and low  sensitivity for diagnosing colorectal cancer.

PMID- 19391230
TI  - University of Chicago Medical Center redefines role, reduces emergency care
      access: critics blast urban health initiative as payer "cherry picking".

PMID- 19391231
TI  - Ignoring it isn't an option: racial bias in emergency medicine.

PMID- 19391232
TI  - Sitagliptin combined with sulphonylureas: new indication. Other treatments are
      preferable.
AB  - In type 2 diabetes, sitagliptin, in combination with a sulphonylurea, only
      provides modest efficacy in terms of HbA1c levels and increases the risk of
      hypoglycaemia.

PMID- 19391233
TI  - Epoetin alfa: biosimilar. Copied, with biosimilar status.
AB  - The first copy of Eprex, a product containing epoetin alfa, has been marketed in
      France, under the name Binocrit.

PMID- 19391234
TI  - Line, please.

PMID- 19391235
TI  - Case study. Waiting it out. Commentary.

PMID- 19391236
TI  - True health care reform remains an elusive goal.

PMID- 19391237
TI  - [Cathepsin D: its physiological role and use in medicine (a review of
      literature)].

PMID- 19391238
TI  - [A procedure for determination of acid mannosidase activities in biological
      fluids].
AB  - A procedure has been developed for simultaneous determination of the activities
      of alpha-D- and beta-D-mannosidase in the biological fluids from the quantity of
      free 4-nitrophenol. The latter is released via enzymatic degradation of
      substrates of 4-nitrophenyl-alpha-D-mannose and 4-nitrophenyl-beta-D-mannose in
      individual incubation tests.

PMID- 19391239
TI  - [Morphometry and electrophoretic mobility of red blood cells from patients with
      asthma in the intravenous blood laser irradiation].
AB  - The morphometry and electrophoretic mobility of red blood cells from patients
      with infection-dependent asthma were comparatively studied prior to and following
      treatment. The patients who had underwent intravenous laser irradiation of blood
      (ILIB) in addition to conventional therapy had better morphofunctional parameters
      of red blood cells, by restoring their normal forms, decreasing their
      transitional ones, and increasing their electrophoretic mobility to normal
      values. Those who received traditional drug therapy showed no considerable
      morphofunctional changes of erythrocytes. Thus, in asthmatic patients, the
      changes in the morphology and function of red blood cells may suggest their
      membranous structural changes for whose correction ILIB should used.

PMID- 19391240
TI  - [Exfoliative cytological diagnosis of lung cancer with bronchoscopic material].
AB  - Analysis of the results of exfoliative cytological diagnosis of lung diseases
      from fibrobronchoscopic materials in the presence of the affected bronchial
      mucosa made it possible to verify lung cancer in 75.9% of cases and to give a
      descriptive reply due to the fact that cytological specimens were of no
      diagnostic value. Further examinations of transthoracic puncture specimens and
      clinical and X-ray findings of patients from the latter group could reveal an
      inflammatory process in two thirds of cases and peripheral lung cancer in a
      third.

PMID- 19391241
TI  - [The levels of soluble CD95 antigen and CD95+ mononuclear cells in patients with
      chronic obstructive lung diseases].
AB  - The levels of soluble CD95 (sCD95) antigen and CD95+ mononuclear cells were
      studied in the peripheral blood, induced sputum (IS), expired air condensate
      (EAC) of patients with chronic obstructive pulmonary disease (COPD). There was an
      increase in the relative count of CD95+ mononuclear cells and a reduction in the
      level of sCD95 antigen in the peripheral blood of patients with severe COPD. The
      elevated levels of sCD95 antigen and CD95+ mononuclear cells were revealed in IS
      and EAC in moderate COPD.

PMID- 19391242
TI  - [The biological and diagnostic implication of the comparative data on expression
      of the same protein, obtained by Western blotting and surface plasmone resonance
      tests].
AB  - The comparative analysis of the data on the expression of the same modulating
      protein MX, obtained on the same biological materials by Western blotting and
      surface plasmone resonance tests was shown to provide in most cases a
      semiquantitative opinion as to modulation of MX affinity to its specific target
      (effector X protein) under the experimental action of F. This is doubtlessly to
      offer additional possibilities for the prediction and differential diagnosis of a
      number of diseases, including cancer.

PMID- 19391243
TI  - [Trends in the development of modern laboratory medicine (a lecture)].

PMID- 19391244
TI  - [Detecting the markers of HIV infection with the new enzyme immunoassay
      diagnostic kit "DS-EIA-HIV-AB-AG-SPECTRUM" at the laboratories of AIDS prevention
      and control centers in the Volga Federal District].
AB  - A possibility of simultaneously detecting specific antibodies to HIV-1 and HIV-2
      by enzyme immunoassay (EIA) at lower concentrations than those by immunoblotting
      (IB), and well as an additional possibility of earlier diagnosis of HIV
      infection, by identifying the HIV-1 antigen p24 lay the foundation of the "DS-EIA
      HIV-AB-AG-SPECTRUM" test system made by OOO "Research-and-Production Association
      "Diagnosticheskiye Sistemy" (Diagnostic Systems). These peculiarities were
      compared with those of IB at a number of laboratories of AIDS prevention and
      control centers in the Volga Federal District, by using native serum/plasma
      samples and a specially designed control panel. The analysis of the conducted
      studies to identify HIV-1 and HIV-2 antibodies and HIV-1 antigen p24 in 65
      plasma/serum samples in the "DS-EIA-HIV-AB-AG-SPECTRUM" and "LIA-HIV-1/2" (OOO
      "Niarmedik plus") test systems while confirming the positive result indicated
      agreement in 57 (87.7%) cases. The diagnostic possibilities of the "DS-EIA-HIV-AB
      AG-SPECTRUM" test system versus the "New Lav-Blot I" one to make a laboratory
      diagnosis of HIV infection were studied. Irrefragable answers as to the
      availability of HIV-1 markers in the study serum samples on the enciphered panel
      were provided by IB in 73.3% of cases and EIA in 92%.

PMID- 19391245
TI  - [Use of enzyme immunoassay to diagnose giardiasis in patients with dermal
      manifestations].

PMID- 19391246
TI  - [Old equipment: to write off or to upgrade?].

PMID- 19391247
TI  - New way to set up propofol infusion.

PMID- 19391248
TI  - Thoracic rib solitary eosinophilic granuloma in a child.
AB  - Eosinophilic granuloma is characterized by single or multiple skeletal lesions
      occurring predominantly in children, adolescents, and young adults, it accounts
      for 70% of Langerhans cell histiocytosis. The common sites are the skull,
      mandible, ribs, spines, and long bones particularly the femur and the humerus.
      Thoracic rib involvement is rarely seen. It was often regarded as malignant soft
      tissue tumor. We report an unusual case of eosinophilic granuloma in a female
      child presented with a solitary lesion at the thoracic rib.

PMID- 19391249
TI  - Nitric oxide reduces vagal baroreflex sensitivity in the late gestation fetus.
AB  - Goals to understand the etiology of essential hypertension have proposed that
      this problem arises, in part, because of changes within brainstem circuits
      involved in arterial blood pressure (ABP) control. It has been suggested that
      nitric oxide (NO) exerts inhibitory influences on the integration of afferent
      discharge from the arterial baroreceptors. This study tested the hypothesis that
      the inhibitory influence of NO on the arterial baroreflex is present in fetal
      life. Fetal baroreflex sensitivity was calculated in fetal sheep, before and
      during the NO-clamp; a technique that permits NO synthase (NOS) blockade with l
      NAME while maintaining basal cardiovascular function with sodium nitroprusside.
      Under halothane anesthesia, five fetal sheep at 0.8 gestation were instrumented
      with vascular catheters. Five days later, fetuses received a range of bolus doses
      of phenylephrine (5-75 microg I.A.) in randomized order either during saline or
      treatment with the NO clamp. Basal fetal ABP and heart rate before (50 +/- 4 mm
      Hg, 170 +/- 3 bpm) or during (51 +/- 4 mm Hg, 173 +/- 3 bpm) the NO-clamp were
      similar. The gradient of the pulse interval-ABP relationship was nearly doubled
      during NOS blockade (14.2 =/- 2.5 versus 7.8 +/- 1.6 ms/mm Hg). The data provide
      in vivo evidence that NO attenuates the sensitivity of the cardiac baroreflex
      during fetal life.

PMID- 19391250
TI  - Neonates born to mothers with preeclampsia exhibit sex-specific alterations in
      microvascular function.
AB  - This study aimed to characterize early neonatal microvascular function after
      preeclamptic pregnancy with respect to infant sex and in utero growth. Peripheral
      microvascular blood flow was examined prospectively from 6 to 72 h of age using
      laser Doppler flowmetry in a cohort of term infants of normotensive women and
      women with late-onset preeclampsia. For male infants, those born to preeclamptic
      women had greater microvascular blood flow at 6 h (p < 0.05) with no change over
      time. Male infants of normotensive women exhibited increasing blood flow with
      time (p = 0.005). Female infants of preeclamptic mothers exhibited similar blood
      flow at 6 h of age to females of normotensive mothers, followed by significantly
      greater blood flow by 72 h (p < 0.001). Altered fetal microvascular structure and
      function in response to maternal preeclampsia may result in sexually dimorphic
      patterns of fetal growth and account for alterations in neonatal microvascular
      adaptation after birth.

PMID- 19391251
TI  - Breathing patterns in preterm and term infants immediately after birth.
AB  - There is limited data describing how preterm and term infants breathe
      spontaneously immediately after birth. We studied spontaneously breathing infants
      >or=29 wk immediately after birth. Airway flow and tidal volume were measured for
      90 s using a hot wire anemometer attached to a facemask. Twelve preterm and 13
      term infants had recordings suitable for analysis. The median (interquartile
      range) proportion of expiratory braking was very high in both groups (preterm 90
      [74-99] vs. term 87 [74-94]%; NS). Crying pattern was the predominant breathing
      pattern for both groups (62 [36-77]% vs. 64 [46-79]%; NS). Preterm infants showed
      a higher incidence of expiratory hold pattern (9 [4-17]% vs. 2 [0-6]%; p = 0.02).
      Both groups had large tidal volumes (6.7 [3.9] vs. 6.5 [4.1] mL/kg), high peak
      inspiratory flows (5.7 [3.8] vs. 8.0 [5] L/min), lower peak expiratory flow (3.6
      [2.4] vs. 4.8 [3.2] L/min), short inspiration time (0.31 [0.13] vs. 0.32 [0.16]
      s) and long expiration time (0.93 [0.64] vs. 1.14 [0.86] s). Directly after
      birth, both preterm and term infants frequently brake their expiration, mostly by
      crying. Preterm infants use significantly more expiratory breath holds to defend
      their lung volume.

PMID- 19391252
TI  - Tissue Doppler derived longitudinal strain and strain rate during the first 3
      days of life in healthy term neonates.
AB  - Tissue Doppler derived longitudinal strain and strain rate were studied in 48
      healthy term neonates by measuring peak systolic strain (PSS) and peak systolic
      strain rate (PSSR) in 18 heart segments on day 1-3 of life. The mean PSS for each
      examination was -21.8% (-22.1, -21.4) [mean (95%CI)], and the mean PSSR was 
      1.78/s (-1.81, -1.74). Age (d), fetal shunts, and heart rate had negligible
      impact on measurements for any segment. The fractional shortening had negligible
      impact on septum and left heart segments and the pulmonary artery pressure had no
      impact on the right heart segments. Values varied significantly between segments
      and individuals, and were lower (closer to zero) in images of low quality than in
      images of high quality (p < 0.05). Both apical and basal segments values were
      lower in the septum and higher in the right ventricle than in the left ventricle
      (p < 0.05), except for no difference between the basal left and right segments
      PSSR. Apical segments values were higher than basal segments values in the right
      ventricle (p < 0.05) but not in the septum or the left ventricle. At present, PSS
      and PSSR are more feasible for quantifying differences between segment groups and
      patient groups than between individuals and segments within individuals.

PMID- 19391253
TI  - The changing face of epidemiology of invasive fungal disease in Europe.
AB  - Invasive fungal diseases (IFDs) are an increasingly common complication in
      critically ill patients in Europe and are frequently fatal. Because of changes in
      treatment strategies and the increased use of antifungal prophylaxis, the
      epidemiology of IFDs has changed substantially in recent years and infections due
      to Candida species are no longer the majority in many institutions. In contrast,
      the emergence of non-Candida IFDs such as aspergillosis, zygomycosis and
      fusariosis has increased. European surveys indicate that Candida albicans is
      responsible for more than half the cases of invasive candidaemia; however, the
      occurrence of non-albicans-related IFDs appears to be increasing. Rates of IFD
      related mortality in Europe depend on the pathogen, geographical location and
      underlying patient characteristics, with rates ranging from 28 to 59% for Candida
      infections and from 38 to 80% for invasive aspergillosis. Early initiation of
      antifungal therapy is critical for improving outcomes; however, this is
      complicated by the difficulty in diagnosing IFDs rapidly and accurately. The
      introduction of new extended-spectrum azole antifungal agents (e.g. voriconazole,
      posaconazole) and echinocandins (e.g. micafungin, caspofungin, anidulafungin) has
      increased the number of therapeutic options for early therapy. Choice between
      agents should be based on a variety of factors, including spectrum of activity,
      adverse events, drug interactions, route of administration, clinical efficacy of
      individual agents and local epidemiology.

PMID- 19391255
TI  - More on reports of esophageal cancer with oral bisphosphonate use.

PMID- 19391256
TI  - More on reports of esophageal cancer with oral bisphosphonate use.

PMID- 19391257
TI  - More on reports of esophageal cancer with oral bisphosphonate use.

PMID- 19391258
TI  - More on reports of esophageal cancer with oral bisphosphonate use.

PMID- 19391260
TI  - Anti-HIV agents. The changing picture of HIV.

PMID- 19391259
TI  - More on reports of esophageal cancer with oral bisphosphonate use.

PMID- 19391261
TI  - Anti-HIV agents.  HAART reduces inflammation in the blood but...

PMID- 19391262
TI  - Anti-HIV agents. Treatment interruption uncovers HIV's attack on the kidneys.

PMID- 19391263
TI  - Side effects and complications. HAART and the safety of the fetus.

PMID- 19391264
TI  - Side effects and complications. French study clears HAART of cancer link in kids.

PMID- 19391265
TI  - Side effects and complications. Risk of deformities very low in infants exposed
      to HAART.

PMID- 19391266
TI  - Recovering evolutionary trees under a more realistic model of sequence 
      evolution.
AB  - We report a new transformation, the LogDet, that is consistent for sequences with
      differing nucleotide composition and that have arisen under simple but asymmetric
      stochastic models of evolution. This transformation is required because existing
      methods tend to group sequences on the basis of their nucleotide composition,
      irrespective of their evolutionary history. This effect of differing nucleotide
      frequencies is illustrated by using a tree-selection criterion on a simple
      distance measure defined solely on the basis of base composition, independent of
      the actual sequences. The new LogDet transformation uses determinants of the
      observed divergence matrices and works because multiplication of determinants
      (real numbers) is commutative, whereas multiplication of matrices is not,except
      in special symmetric cases. The use of determinants thus allows more general
      models of evolution with a symmetric rates of nucleotide change. The
      transformation is illustrated on a theoretical data set (where existing methods
      select the wrong tree) and with three biological data sets: chloroplasts,
      birds/mammals (nuclear), and honeybees ( mitochondrial ) . The LogDet
      transformation reinforces the logical distinction between transformations on the
      data and tree-selection criteria. The overall conclusions from this study are
      that irregular A,C,G,T compositions are an important and possible general cause
      of patterns that can mislead tree-reconstruction methods, even when high
      bootstrap values are obtained. Consequently, many published studies may need to
      be reexamined.

PMID- 19391267
TI  - Trend of growth of Muslim population in India, 1951-1991.

PMID- 19391268
TI  - Spatial patterns of change in Indian sex ratio: 1981-91.

PMID- 19391269
TI  - Water wars over Litani River.

PMID- 19391270
TI  - Local pottery and dairying at the DMR site, Brickfields, Sydney, New South Wales.

PMID- 19391271
TI  - The potential for the archaeological study of clay tobacco pipes from Australian
      sites.

PMID- 19391272
TI  - Buttoning down archaeology.

PMID- 19391273
TI  - Colonial sanitation, urban planning and social reform in Sydney, New South Wales
      1788-1857.

PMID- 19391274
TI  - A hidden cultural landscape: colonial Sydney's plant microfossil record.

PMID- 19391275
TI  - A professional association as network and communicating node: the Pharmaceutical
      Society of Australasia, 1857-1918.

PMID- 19391276
TI  - Tied houses, taxes, and technology: concentration in the brewing industry of New
      South Wales, 1882 to 1932.

PMID- 19391277
TI  - Rivastigmine patches: line extension. No therapeutic advantage and less
      convenient than capsules.

PMID- 19391278
TI  - [Update hepatology in 2008].

PMID- 19391279
TI  - [Prospect of liver fibrosis].

PMID- 19391280
TI  - [Prospect of hepatocellular carcinoma in 2008].

PMID- 19391281
TI  - [Prospect of severe hepatitis and liver failure].

PMID- 19391282
TI  - [My opinion on the surgical development of gastric cancer in 21 century].

PMID- 19391283
TI  - [Key problems about comprehensive treatment to gastric cancer].

PMID- 19391284
TI  - Patient education program slashes ED readmissions.
AB  - Boston University Medical Center's ED saw 30% fewer readmits after the
      implementation of a new patient education discharge program. The program has
      several key elements that contributed to its success, including: Customized
      booklets for each patient, with information specific to their disease or injury,
      their medications, and follow-up appointments. Charts in which patients can track
      important data, such as their blood sugar levels. Contact by a pharmacist two to
      four days after discharge to reinforce the key education messages.

PMID- 19391285
TI  - Time to roll out rapid testing for HIV? Yes, but with appropriate safeguards.

PMID- 19391286
TI  - 'Tissue paper sign': a highly specific marker of gonococcal urethritis in males.

PMID- 19391287
TI  - Accepted: additional critical access hospital requirement changes, effective Mar
      1, 2009.

PMID- 19391288
TI  - Drug-induced Lyell and Stevens-Johnson syndromes.
AB  - 1) Lyell syndrome is characterised by toxic epidermal necrolysis in which
      epidermal detachment affects more than 30% of the body surface area. Stevens
      Johnson syndrome is a minor form affecting less than 10% of the body surface
      area; 2) Patients who present with these cutaneous symptoms, along with throat
      pain, red eyes and a damaged or detached oral mucosa must be hospitalised
      immediately; 3) Lyell syndrome is exclusively caused by drugs while Stevens
      Johnson syndrome can also be caused by bacteria and viruses. Rapid withdrawal of
      the drug improves prognosis.

PMID- 19391289
TI  - Buprenorphine and pregnancy.

PMID- 19391290
TI  - Bisphosphonates: bone, muscle and joint pain.
AB  - 1) Comparative trials and reports by healthcare professionals show that severe
      and sometimes incapacitating muscle, joint and bone pain can occur days, months
      or years after beginning long-term oral bisphosphonate therapy. Patients treated
      for osteoporosis are particularly at risk; 2) This type of pain affects between
      2% and 5% of patients, especially those taking an oral bisphosphonate once a
      week; 3) The role of a bisphosphonate should be considered when a patient
      presents with musculoskeletal pain. Discontinuation of bisphosphonate therapy can
      be tried and may represent a better option than escalation of analgesic therapy.

PMID- 19391291
TI  - Rimonabant: depression and suicide.
AB  - Pharmacovigilance has revealed hundreds of reports of neuropsychiatric disorders
      and several deaths by suicide.

PMID- 19391292
TI  - Mycophenolate: miscarriage and birth defects.
AB  - About 30% of pregnancies exposed to mycophenolate end in miscarriage. When the
      pregnancy continues, about 20% of foetuses and newborns have malformations of
      various types.

PMID- 19391293
TI  - Fungal nail infections: diagnosis and management.
AB  - 1) Fungal nail infection, or onychomycosis, mainly affects toenails. Infections
      are generally asymptomatic. Spontaneous regressions, but also complications,
      appear to be rare. Discomfort and cosmetic complaint are occasionally reported;
      2) After a review of the literature based on the standard Prescrire procedure, we
      examined the diagnosis and management of fungal nail infections; 3) Clinical
      signs of fungal nail infections are non-specific. Alternative diagnoses include
      psoriasis and nail microtrauma. Nail hyperkeratosis and leukonychia are useful
      diagnostic pointers. Matrix involvement has important implications in the choice
      of treatment; 4) Detection of fungal structures by direct examination of a nail
      sample is strongly suggestive of fungal nail infection. In contrast, cases of
      negative direct examination with positive culture must be interpreted with
      caution, as contamination is frequent; 5) Antifungal lacquers (5% amorolfine and
      8% ciclopirox) applied to the nails cure about 30% of fungal infections and
      sometimes cause mild irritation. There is no firm evidence that these solutions
      are any more effective than other topical antifungals applied daily to the
      affected nail. Trimming, filing or grinding the nail, in addition to these drug
      treatments, is likely to be beneficial, but these measures have not been
      evaluated; 6) Chemical nail destruction with a combination of urea and
      bifonazole, followed by treatment with an antifungal ointment, can be used when
      the nail is markedly thickened. Non-comparative trials have shown cure rates
      close to 70% at three months when the matrix is not involved, and 40% with matrix
      involvement. Drug application is inconvenient and local reactions are frequent.
      Surgical nail avulsion carries a risk of local infection and permanent nail
      dystrophy; 7) Oral terbinafine is effective in more than 50% of cases but its
      cutaneous, hepatic and haematological adverse effects are severe in about 1 in
      2000 patients and can be life-threatening; 8) It is better to treat Candida nail
      infections with oral azoles (ketonazole, itraconazole) than with terbinafine.
      These treatments carry a risk of serious adverse effects and numerous drug
      interactions; 9) Fungal nail infections are usually mild. Treatments with
      potentially severe adverse effects must therefore be used with caution. It is
      better not to treat fungal nail infections if the risks outweigh the expected
      benefits.

PMID- 19391294
TI  - The common cold.
AB  - 1) Most colds are due to viruses and resolve spontaneously after a few days.
      Available drugs do not modify the course of a viral cold; 2) Some drugs used to
      treat colds carry a risk of serious adverse effects. This includes nasal sprays,
      especially vasoconstrictors such as pseudo-ephedrine and, in young children,
      menthol, camphor, and terpene derivatives.

PMID- 19391295
TI  - A long-run analysis of cooperative housing societies and housing construction in
      Victoria, Australia.

PMID- 19391296
TI  - Management of primary liver cancer.
AB  - 1) Hepatocellular carcinomas represent approximately 90% of all primary cancers
      of the liver. In 80% of cases, these cancers develop in patients with cirrhosis
      (of viral origin or due to other causes); 2) Numerous treatments have been
      proposed (transplantation, surgical resection, percutaneous ablation, arterial
      embolisation, chemotherapy) either alone or in combination; 3) Adverse effects
      are frequent, varied and often serious. Efficacy is highly variable, depending on
      tumour size, liver function and the patient's health status. As of 2008, little
      comparative evaluation of these treatments has been performed; 4) In practice,
      surgery is the treatment of choice for small, solitary tumours. In other cases,
      choosing the most appropriate treatment is particularly tricky, and depends on
      the individual case.

PMID- 19391297
TI  - Do migrants rob jobs? New evidence from Australia.

PMID- 19391298
TI  - Diet replenishment for ad-libitum-fed mice housed in social groups is compatible
      with shelf life.

PMID- 19391299
TI  - Imagined peasants: production and markets in rural Asia.

PMID- 19391300
TI  - Antioxidants: not for prevention.
AB  - In spite of substantial evaluation, the preventive effect of antioxidants remains
      hypothetical. Some antioxidants have been associated with higher mortality rates.

PMID- 19391301
TI  - Convention and contradiction: representations of women in Australian war films,
      1914-1918.

PMID- 19391302
TI  - Food as nostalgia: eating the fifties and sixties.
AB  - This article traces examples of remembered food cultures of the 1950s and 1960s
      in Australia, as starting points for addressing their mythic re-inscription in
      the 1990s. Analysing iconic images from cookbooks, positioned against fragments
      of women's remembering, the article suggests the need for more complex narratives
      than those of nostalgic returns to secure suburban pasts or of thankful culinary
      escapes towards multiculturalism and cosmopolitan identity.

PMID- 19391303
TI  - Whither speech rhythm research?

PMID- 19391304
TI  - [Introduction].

PMID- 19391305
TI  - Letters from Mapoon: colonising Aboriginal gender.
AB  - Much information on traditional indigenous society in Australian historiography
      and anthropology stems from the vast store of eyewitness accounts left by
      missionaries, settlers and government officials. How cautious does one need to be
      in using such material? After all that it reveals about the moral and legal
      universe of its writers, can it speak reliably about traditional society? This
      article traces the production of knowledge about indigenous gender relations at
      Cape York Peninsula through a lineage of sources from the 1890s to the 1990s and
      concludes that unless the assumptions embedded in the primary sources are clearly
      identified, the discourse on Aboriginal womanhood continues to be a colonising
      project.

PMID- 19391306
TI  - Media and science: harmless dioxin, benign CFCs, and good asbestos.

PMID- 19391307
TI  - Neurogenic inflammation: additional points.

PMID- 19391308
TI  - Molar-incisor-hypomineralisation: site specific or world wide problem?

PMID- 19391309
TI  - Therapeutic monitoring of drug plasma concentrations and improved clinical
      outcomes in CML.

PMID- 19391310
TI  - Therapeutic monitoring of drug plasma concentrations and improved clinical
      outcomes in GIST.

PMID- 19391311
TI  - Promises and pitfalls of oral cancer chemotherapy.

PMID- 19391312
TI  - Validation of elimination of neonatal tetanus in Turkey by lot quality assurance
      cluster sampling.

PMID- 19391313
TI  - Integrated control of neglected   zoonotic diseases in Africa.

PMID- 19391314
TI  - The acceptance rate of intrauterine contraceptive device (IUCD) amongst family
      planning clinic users in Lagos University Teaching Hospital (LUTH).
AB  - BACKGROUND: Intrauterine Contraceptive Device is an effective reversible long
      term contraceptive method that is popular and widely used in this environment.
      OBJECTIVES: To determine the characteristics of women using this mode of
      contraception, their main reasons for acceptance, complications arising from
      usage and the discontinuation rate as well as reasons for discontinuing the
      method. METHODS: A review of case records of all the new contraceptive acceptors
      attending the Department of Obstetrics and Gynaecology Family Planning Clinic of
      the Lagos University Teaching Hospital (LUTH) from 1st January 1990 to 31st
      December 1994 was examined and the clients that accepted the intrauterine
      contraceptive device, (IUCD) during this period were identified. The records of
      those that opted for IUCD were thoroughly reviewed to identify the follow up
      events through the subsequent ten years visits to determine outcome of the
      contraceptive usage. RESULTS: Amongst the 2754 new contraceptive acceptors during
      the study period, 1602 (58.17%) clients accepted the Intrauterine Contraceptive
      Device (IUCD). Of these IUCD acceptors, the mean age was 31.3 +/- 5.5 years, mean
      parity was 3.9 +/- 2 and mean number of children alive was 3.6 +/- 1.8. Seven
      hundred and forty nine (46.8%) of them had previously used contraceptives and
      1175 (73.3%) of them still wanted more children, thus child spacing was the main
      reasons for accepting this method. By 12 months, the discontinuation rate was
      13.9% with the cumulative discontinuation rate of 47% as at forty-eighth month.
      The commonest reason for discontinuation was planning to get pregnant in 426
      (26.6%) of the clients. Menstrual disorders accounted for 108 (6.7%). The mean
      duration of IUCD was 25.4 +/- 18.8 months with an accidental pregnancy rate of
      0.3%. CONCLUSION: Intrauterine Contraceptive Device is widely accepted amongst
      women in the study group. Devices that reduce menstrual loss and also have long
      duration of action like Levonorgestrel intrauterine system (LNG-IUS) qualifies to
      be considered.

PMID- 19391315
TI  - Pre-induction hypokalaemic phenomenon in Nigerian adult population.
AB  - BACKGROUND: Anaesthesia in the perioperative period is characterized by acute
      changes in plasma potassium (K+) which may be caused by anxiety. Anxiety leads to
      an intracellular shift of potassium which may lead to hypokalaemia. These
      fluctuations in plasma potassium may sometimes induce arrhythmias. This study was
      designed to determine the acute changes in plasma potassium levels in the
      immediate pre-induction period in a sample of Nigerian patients and to determine
      the incidence of arrhythmias correlating with these changes. METHODS: Sixty ASA I
      and II adults aged 14 to 70 years, both genders, undergoing elective surgery
      under general anaesthesia at the Lagos University Teaching Hospital were
      prospectively and consecutively recruited. Preoperative plasma potassium level
      was determined 1-3 days before surgery. Premedication was with oral diazepam 10
      20 mg given nocte and on the morning of surgery. Pre-induction plasma potassium
      level was determined within 5 minutes before induction of anaesthesia. RESULTS:
      Mean preoperative K+ was 3.98 +/- 0.38 mEq.L(-1) (range of 3.5 - 4.9 mEqL(-1)).
      The mean pre-induction plasma K+ level was 3.01 +/- 0.35 mEq.L(-1) (range of 2.1 
      3.6). This represented a fall of 24% (0.97 +/- 0.39 mEq.L(-1)) which was
      significantly different (p < 0.001). More than 80% of the patients exhibited some
      fall in plasma K+. No arrhythmias were recorded during the study period.
      CONCLUSION: Pre-induction hypokalaemia occurred frequently despite the
      administration of anxiolysis with diazepam. There is a need to consider this
      phenomenon and measure K+ levels immediately pre-induction especially in patients
      with existing borderline normal K+ levels.

PMID- 19391316
TI  - Students' view of a learning method: opinions of first year medical and dental
      students in the School of Basic Medical Sciences of University of Lagos, Nigeria,
      about problem based learning.
AB  - BACKGROUND: Driven by a desire to improve basic medical science education, the
      department of Anatomy in the College of Medicine University of Lagos introduced
      the Problem Based Learning (PBL) programme into the Anatomy component of first
      year Basic medical science training of the College of Medicine, University of
      Lagos. OBJECTIVE: We conducted a students' assessment of the different aspects of
      this newly introduced PBL. METHODS: Structured questionnaires were circulated
      among first year Medical and Dental students in the School of Basic Medical
      Sciences of the University. Apart from relevant personal data that would not
      compromise identity of respondents, we sought to find out through relevant
      questions students' opinion about various aspects of the programme. The
      respondents had to grade their responses on a scale of 1 through 5 (representing
      strongly agree to strongly disagree) to indicate their level of agreement/
      disagreement to simple statements designed as completions to a single stem
      statement. RESULTS: The class generally rated the use of PBL and the activity of
      the department in the programme high whilst also highlighting the areas of
      challenges where some major improvements needed to be observed. CONCLUSION: The
      established benefits of the PBL approach are reproducible even when implemented
      newly in a challenging and often times difficult environment in a developing
      country.

PMID- 19391317
TI  - Haemosuccus pancreaticus as a rare initial manifestation of pancreatic carcinoma.
AB  - BACKGROUND: The major symptoms of cancer of the pancreas, even those of the head,
      are insidious weight loss, abdominal pains, back pain, anorexia, nausea, vomiting
      and generalized malaise. Jaundice is present in about 90% of the patients with
      cancer of the head and 10-40% of those with cancer of body and tail. Massive
      haemorrhage is an uncommon presentation. Most causes of G. I haemorrhage respond
      to conservative treatment. Haemosuccus Pancreaticus is a care cause of
      gastrointestinal hemorrhage and can prove difficult to diagnose. OBJECTIVE: To
      highlight the carcinoma of the head of pancreas as a possible cause of massive
      upper G.I haemorrhage. METHODS: Case 1: Mr. H. A., a 32 year old man who
      presented with repeated episodes of massive upper G. I. hemorrhage for which he
      was transfused on several occasions. He later presented in shock, was
      resuscitated and had emergency laparatomy. case 2: Miss B.O, A 30 year old lady
      presented with massive upper G.I hemorrhage not responsive to conservative
      measures. She had exploratory laparotomy and findings were bleeding pancreatic
      tumour that eroded into the duodenum. RESULTS: Both patients were found to have
      pancreatic caranoma with bleding into the pancreatic ducts. CONCLUSION:
      Haemosuccus pancreaticus may present as one of the early symptoms of carcinoma of
      the pancreas in young patients in our environment.

PMID- 19391318
TI  - Effect of methanolic extract of Neem leaf (Azadirachta indica) on ovarian
      histology and hormonal milleu.
AB  - BACKGROUND: Extract of neem leaves is commonly consumed as an antimalarial
      therapy. OBJECTIVES: This study was designed to investigate the effect of
      methanolic extract of neem leaves on the histology of the ovary and also on serum
      levels of FSH and LH in female Wistar rats. METHODS: A total of eighteen (18)
      rats weighing 110g-150g were used. They were randomly divided into three groups
      (A, B, and C) of six rats each. Group A: served as control and received distilled
      water equivalent in volume to the test extract. Group B: was treated with
      200mg/kg of the methanolic extract of neem leaves. Group C: received 400mg/kg of
      the methanolic extract of neem leaves. Administration was by gavage and lasted
      for a period of 14 days. RESULTS: Histological sections of the experimental
      groups revealed no histopathological features. No statistically significant
      difference was observed in the serum levels of FSH in the treated groups.
      However, serum levels of LH were significantly reduced when compared with the
      control. CONCLUSION: The study revealed that extract of neem leaves may affect
      fertility adversely by reducing serum levels of LH and subsequently, the release
      of ova during ovulation.

PMID- 19391319
TI  - Immunophenotypical categorization of omental and liver metastatic tumours in
      Lagos, Nigeria.
AB  - INTRODUCTION: Immunohistochemistry(IHC), used routinely in developed countries to
      identify primary sites of metastatic tumours has scarcely available I Nigeria
      where majority of patients present with advanced metastases. This study was aimed
      at evaluating the use of immunohistochemistry in differential diagnosis of
      omental and liver metastases. MATERIALS AND METHODS: Materials consisted of the
      formalin fixed paraffin embedded blocks of omental and liver metastatic tumours
      diagnosed in Lagos between January 1995 and February 2007. Ethical clearance was
      obtained and sections were stained with CK 7, CK20, CA-125, ER, PSA, and TTF1
      antibodies at the research Laboratory of The Leeds General Infirmary, United
      Kingdom following standard procedure. RESULTS: A total of 83 cases of omental
      (67) and liver (16) metastatic tumours were identified representing 11.6% of all
      gastrointestinal (GIT) malignancies. Immunostaining was carried out on 44 cases
      (53%) consisting of 32 (75%) of omental and 11 (25%) of liver tumours; M: F of
      1.4:1 and mean age of 43 years. They were categorized as arising from the upper
      GIT (CK7 +/CK20-) in 17(38.6%), lower GIT (CK20+/CK7-) in 16 (36.3%),
      gynaecological (CA-125+/ER+) in 4 (9.1%). One case each was categorized as
      arising from the prostate (PSA+) and breast (ER+) and lung (TTF-1+) while one
      with histological appearance of neuro-endocrine was focally positive for both CK7
      and CK20. Three liver metastases negative for all the 6 antibodies could not be
      classified. CONCLUSION: This study has further corroborated previous studies that
      adenocarcinoma is the most common metastatic omental and liver metastases and the
      common primary sites are within the gastrointestinal tract. Since many patients
      in Africa present late with advanced metastases, immunohistochemistry is will be
      useful in identifying primary sites before initiating specific treatment.

PMID- 19391320
TI  - Comparison of electrical stimulation and conventional physiotherapy in functional
      rehabilitation in Erb's palsy.
AB  - BACKGROUND AND PURPOSE: Erb's Duchenne paralysis constitutes the single commonest
      form of brachial plexus injury. Treatment intervention is mainly by physical
      therapy and surgery. Popular or conventional physiotherapy approaches include
      exercise therapy, tactile stimulation, soft tissue manipulation techniques and
      functional splinting. The role of electrical stimulation has been reported in
      literature but not without differing opinions on its efficacy in early resolution
      of infantile Erbs palsy. OBJECTIVES: The purpose of this study is to compare the
      effects of electrical stimulation and conventional physiotherapy in the early
      resolution of function in infantile brachial plexus lesion. METHODS: Sixteen
      subjects who were diagnosed to have Erb's palsy were assigned randomly into two
      groups; A (n = 8) and B (n = 8). While group A was treated with electrical
      stimulation, group B had conventional physiotherapy treatment. Both groups were
      seen three times weekly and the study lasted 6 weeks. Four functional variables
      measured include (a) Shoulder Abduction, (b) Elbow flexion, (c) Wrist extension
      and (d) Arm circumference (6cm distal to the acromion process). These were
      evaluated at the baseline (pre-study), 3 weeks into the study and 6 weeks (end of
      study) periods. RESULTS: Functional variables did not differ significantly among
      the groups at the baseline (p > 0.05), shoulder range of motion showed
      significantly higher increase in group A. At the end of the 6-week intervention,
      statistically significant differences, with higher increase in group A than group
      B, were found in all the variables. CONCLUSION: The outcome of this study
      suggests that functional electrical stimulation may be preferred to conventional
      approach in the course of rehabilitation for an early resolution of function in
      Erbs paralysis.

PMID- 19391321
TI  - Comparing the knowledge and attitude about HIV/AIDS and the sexual behaviour of
      secondary school students of a missionary school and a public school.
AB  - BACKGROUND: A study of high school students attending a missionary school and a
      public school in Lagos was carried out to determine their knowledge and attitude
      about HIV/AIDS and to compare their sexual behaviour. METHODS: Self administered
      questionnaires, were used for the respondents, selected by multistage sampling
      and a response rate of 98% was obtained. The average age of the population was
      13.6 years. There was no significant difference in the knowledge of students from
      both schools about HIV/AIDS. 90% of all the respondents knew the exact meaning of
      HIV/AIDS. Most of the students got their information from the mass media (66%)
      and the school (57%). Only 5% and 0.3% of missionary and public school students
      respectively were informed by their parents. RESULTS: There was no significant
      statistical association between the type of school and the occurrence of sexual
      intercourse. However, only 4% of sexually active missionary students used condoms
      compared to the 37% of the public school students. Condom usage was associated
      with the type of school (X2 = 1830; P-value = 0.0000189). There was also a
      statistically significant relationship between condom use and the age, sex and
      class of sexually active students (P-value = 0.00000006; 0.00000032; 0.00497073
      respectively). 25% of the sexually public students had multiple sexual partners,
      compared to 2% for the missionary school students. There was a statistically
      significant relationship between the type of school and the number of sexual
      partners (X2 = 11.37; P-value = 0.003390). CONCLUSION: The study recommends that
      age-appropriate comprehensive sexuality education (including condom use) should
      be made available to students from both schools.

PMID- 19391322
TI  - Hypoglycemic and hypolipidemic effects of methanol seed extract of Citrus
      paradisi Macfad (Rutaceae) in alloxan-induced diabetic Wistar rats.
AB  - BACKGROUND: Alcohol decoction of Citrus paradisi Macfad (Rutaceae) seed is
      reputed for the local management of array of human diseases including, anemia,
      diabetes mellitus and obesity by some Yoruba herbalists (SouthWest, Nigeria).
      Despite its historic use, scientific evaluation of its folkloric use in the
      management of diabetes mellitus is scarce. OBJECTIVES: The present study was
      designed at investigating the glucose and lipid lowering effects of methanol seed
      extract of Citrus paradisi Macfad (MECP) in alloxan-induced diabetic rats. In
      addition, the phytochemical analysis of the extract was also conducted using
      standard procedures. METHODS: Young adult, male, alloxan-induced diabetic rats
      were randomly divided into groups I - VI with 12 rats in each group. Group I rats
      were the normal untreated rats while group II rats served as the diabetic
      untreated rats while Rats in groups III - VI served as diabetic rats treated with
      100, 300 and 600 mg/kg/day MECP and 20 mg/kg/ day metformin, respectively, for 30
      days. On the 15th and respectively, 31st day, blood samples from the fasted rats
      were obtained for fasting plasma glucose (FPG), plasma triglycerides (TG), total
      cholesterol (TC), high density lipoprotein- cholesterol (HDL-c), low density
      lipoprotein-cholesterol (LDL-c) and very low density lipoprotein-cholesterol
      (VLDL-c) from the sacrificed rats. RESULTS: Oral treatment with 100 - 600
      mg/kg/day MECP, for 30 days, resulted in significant (p < 0.05, p < 0.01, p <
      0.001) reductions in FPG, TG, TC, LDL-c, VLDL-c in the diabetic rats, effects
      which were comparable to that of metformin. The extract also caused significant
      (p < 0.05, p < 0.01) rise in HDL-c values in the alloxan diabetic rats.
      Phytochemical result showed the presence of alkaloids, flavonoids, cardiac
      glycosides, tannins and saponin in varying concentrations. The biological effects
      recorded for the extract could be due to any or a combination of these
      phytochemical constituents. CONCLUSION: Results of this study lend support to the
      traditional use of grapefruit seeds in the management of type 1 diabetic patients
      and may suggest a role in orthodox management of the disease.

PMID- 19391323
TI  - Recent technological developments in the clinical application of ionizing
      radiations.

PMID- 19391324
TI  - Post operative nausea and vomiting in adult Nigerians.
AB  - BACKGROUND: This is a prospective study to determine the pattern of postoperative
      nausea and vomiting in a Nigerian adult population. METHOD: 348 consecutive
      patients were assessed prospectively for the incidence and risk factors of
      postoperative nausea and vomiting over a 6-month period. The exclusion criteria
      included inability to give consent, nausea or vomiting during the period 24 hours
      before surgery, raised intracranial pressure and patients who received an anti
      emetic in the period 48 hours before surgery. RESULT: Patient's age ranged
      between 18 and 90 years. There were 213 females (61.2%) and 135 males (38.8%).
      The incidence of postoperative nausea was 32.2% and vomiting was 20.1%. The major
      risk factors identified were female gender, body mass index, general anaesthesia
      inhalational technique, Ketamine induction, pancuronium, pain and movement of
      patients from the recovery room to surgical wards (p < 0.05). CONCLUSION: Nausea
      and vomiting was identified as a common postoperative complication with
      multifactoral aetiology. It is recommended that high risk patients should receive
      prophylactic antiemetics. Regional techniques should also be considered in such
      patients.

PMID- 19391325
TI  - Experiences of patients with chronic low back disorder of the use of spinal
      stabilisation exercises--a qualitative study.
AB  - BACKGROUND: There is limited evidence on the patients' perception of the
      treatment with spinal stabilisation exercises and their overall experience of the
      treatment programme. OBJECTIVE: The aim of this study was to elicit valuable
      information of the experiences of patients who participated in a spinal
      stabilisation programme within a randomised controlled trial (RCT). METHOD: A
      qualitative study. PARTICIPANTS: Nine participants (male = 3, female = 6) were
      selected, to participate in focus group interviews from among those who
      participated in the RCT on the use of stabilization exercises in the treatment of
      chronic low back pain. A semi-structured interview comprising of open ended
      questions were used. Audio recording was used to record participants' opinions
      during the interview process. Careful checking, reading and correction of the
      transcript from the interviews were carried out and a thematic analysis was
      conducted on the data. RESULTS: Participant's explanations for the perceived
      improvements were not limited to the positive effects of stabilisation exercise
      on pain severity, functional disability and quality of life but also reflected
      major increases in confidence and the formulation of self help strategies and the
      ability to exert better control over their back pain due to more knowledge of the
      spine and how it works. CONCLUSION: Participants views on the benefit of
      stabilisation exercise programme are heterogeneous. However, the opinions of many
      of the participants in this study seem to have indicated satisfaction with the
      programme.

PMID- 19391326
TI  - Effect of pine bark (Pinus radiata) extracts on sporulation of coccidian oocysts.
AB  - A series of experiments have been undertaken to determine the effect of water
      extracts from pine bark (Pinus radiata) on the inhibition of the sporulation of
      oocysts of three species of avian coccidia. Tubes containing coccidian oocysts
      isolated from droppings of coccidia-infected chickens were randomly assigned to
      0, 250, 500 and 1000 microg/ml pine bark extract (PBE). The tubes were incubated
      at 25-29 degrees C for 48 h depending on the species of Eimeria. Sporulation
      inhibition bioassay was used to evaluate the activity of PBE on the sporulation
      of coccidian oocysts. The oocysts were gently aerated with an air pump away from
      sun light. The results show for the first time that water-soluble extracts from
      pine bark containing 35% condensed tannins have anticoccidial activity as
      evidenced by their ability to decrease significantly the sporulation of the
      oocysts of three species of Eimeria, namely Eimeria tenella (Railliet et Lucet,
      1891), E. maxima Tyzzer, 1929 and E. acervulina Tyzzer, 1929, under laboratory
      conditions. Incubation of unsporulated oocysts of these parasites in water
      containing 500 microg PBE per ml resulted in inhibition of sporulation of these
      oocysts by about 28-84% relative to the oocysts in the control incubations. In
      addition, up to 12% of E. maxima oocysts exposed to 500-1000 microg pine bark/ml
      were containing abnormal sporocysts in terms of size, number and shape.

PMID- 19391327
TI  - The life cycle of Myxobolus lentisuturalis (Myxozoa: Myxobolidae), from goldfish
      (Carassius auratus auratus), involves a Raabeia-type actinospore.
AB  - We studied a natural infection of the oligochaete Branchiura sowerbyi Beddard,
      1892 with the Raabeia-type actinosporean stage of Myxobolus lentisuturalis
      Dykova, Fiala et Nie, 2002 which infected goldfish Carassius auratus auratus (L.)
      in Italy, using molecular analysis of the SSU rRNA gene. The existence of
      intraoligochaete development shows that this parasite follows the life-cycle
      pattern described by Wolf and Markiw (1984) for Myxobolus cerebralis.
      Histological examinations of the goldfish infected by M. lentisuturalis showed at
      low magnification the presence of two bilateral crescent-shaped masses in the
      dorsal epaxial muscle. These lesions were not circumscribed, presented irregular
      edges and infiltrated the underlying bundles of skeletal muscle and interstitial
      tissue. At higher magnification, disappearance of muscle fibres and substitution
      of the muscle tissue with Myxobolus spores and plasmodia were observed.

PMID- 19391328
TI  - Gyrodactylus orecchiae sp. n. (Monogenea: Gyrodactylidae) from farmed populations
      of gilthead seabream (Sparus aurata) in the Adriatic Sea.
AB  - Gyrodactylus orecchiae sp. n. (Monogenea, Gyrodactylidae) is described from the
      skin, fins, eyes and gills of juvenile Sparus aurata L. (gilthead seabream)
      following two outbreaks of gyrodactylosis amongst stocks held in inshore floating
      cages on the Adriatic coast of Albania and Croatia. Fish were heavily infected
      (1000+ gyrodactylids/fish) with G. orecchiae which reportedly resulted in
      approximately 2-10% mortality amongst the infected stock. Morphologically, the
      haptoral hooks of G. orecchiae most closely resemble those of Gyrodactylus
      arcuatus Bychowsky, 1933 in the approximate shape of the ventral bar with its
      pronounced ventral bar processes and marginal hook sickles which possess a square
      line to the inner edge of the sickle blade and large rounded heels. The marginal
      hooks are also morphologically similar to those of Gyrodactylus quadratidigitus
      Longshaw, Pursglove et Shinn, 2003 and Gyrodactylus colemanensis Mizelle et
      Kritsky, 1967, but G. orecchiae can be readily discriminated from all three
      species by the characteristic infolding of the hamuli roots and the shape of the
      marginal hook sickle. Molecular sequencing of the ITS1, 5.8S, ITS2 regions
      (513+157+404 bp, respectively) of G. orecchiae and alignment with other
      gyrodactylids for which these same genomic regions have been determined, suggests
      that this is a new species. No similarities were found when the ITS1 region of G.
      orecchiae was compared with 84 species of Gyrodactylus available on GenBank.

PMID- 19391329
TI  - Two new species of Neoentobdella (Monogenea: Capsalidae: Entobdellinae) from the
      skin of Australian stingrays (Dasyatidae).
AB  - Two new species of entobdelline (capsalid) monogeneans are described from the
      skin of Australian dasyatid stingrays, namely Neoentobdella cribbi sp. n., a
      small parasite from the estuarine stingray, Dasyatis fluviorum Ogilby
      (Elasmobranchii: Dasyatidae) and Neoentobdella baggioi sp. n., a relatively large
      parasite from the porcupine ray, Urogymnus asperrimus (Bloch et Schneider)
      (Elasmobranchii: Dasyatidae). A striking feature of both of these new parasite
      species is a pad, possibly located within the genital atrium, armed with rows of
      closely spaced, rod-shaped microsclerites. Both species also possess a muscular
      papilla in the genital tract and a club-shaped structure near the common genital
      opening on the left lateral margin of the body. In N. cribbi, the latter feature
      is large and located anterior to the genital pad and in N. baggioi, it is small
      and located in a more posterior position. Similar embellishments in the genital
      area occur in N. natans Kearn et Whittington, 2005 and in N. parvitesticulata
      Kearn et Whittington, 2005, while other species (e.g. N. garneri Whittington et
      Kearn, 2009 and N. taiwanensis Whittington et Kearn, 2009) lack these features
      and differ also in functional aspects of the male copulatory apparatus and the
      haptor. Separate generic status for these two groupings is indicated, but must
      await a comparative and comprehensive review of all Neoentobdella spp.

PMID- 19391330
TI  - Philometrids (Nematoda: Philometridae) from fishes of Lake Turkana, Kenya,
      including two new species of Philometra and erection of Afrophilometra gen. n.
AB  - The following four species (only females available) of the Philometridae
      (Nematoda: Dracunculoidea) were recorded from freshwater fishes of Lake Turkana,
      northwestern Kenya in 2007-2008: Philometra bagri (Khalil, 1965) from the
      subcutaneous tissue around the mouth, on gill covers and the fin base of the
      bayad Bagrus bajad (Forsskal) (Bagridae: Siluriformes), Philometra lati sp. n.
      from the abdominal cavity of the Nile perch Lates niloticus (Linnaeus) (Latidae:
      Perciformes), Philometra spiriformis sp. n. from capsules on the inner surface of
      gill covers of L. niloticus and Afrophilometra hydrocyoni (Fahmy, Mandour et El
      Nafar, 1976) comb. n. from the fins of Hydrocynus forskahlii (Cuvier) (Alestidae:
      Characiformes). The new species P. lati is characterized mainly by the presence
      of distinct oesophageal teeth, absence of large cephalic lobes and caudal
      projections, and by a combination of other features. Philometra spiriformis
      differs from all congeners principally in the spirally coiled body and from
      individual species by a combination of other morphological features. The already
      known species P. bagri and A. hydrocyoni are redescribed based on light and
      scanning electron microscopy; findings of both these species in Kenya represent
      new geographical records.

PMID- 19391331
TI  - Goezia spinulosa (Nematoda: Raphidascarididae), a pathogenic parasite of the
      arapaima Arapaima gigas (Osteichthyes).
AB  - The nematode Goezia spinulosa (Diesing, 1839) (Raphidascarididae) is redescribed
      based on specimens found in the stomach and intestine of the naturally infected
      arapaima Arapaima gigas (Schinz) from the Mexiana Island, Amazon River Delta,
      Brazil. Light and electron microscopy examinations revealed some previously
      unreported or inaccurately described morphological features in the species, such
      as the position of the excretory pore, phasmids in the male or the number (4) of
      postanal papillae. The morphology of G. spinulosa is compared with that of other
      four congeneric species parasitizing freshwater fishes in South America. This
      nematode seems to be one of the most pathogenic parasites of A. gigas in the
      Mexiana Island, which are responsible for a high mortality of cultured arapaima
      fingerlings. Apparently, the source of G. spinulosa infection for arapaima
      fingerlings cultured in tanks was the infected plankton collected in the
      localities inhabited by wild arapaimas. Therefore, control measures should
      include the sterilisation of the plankton before its use as food for fish. A rare
      infection of Eustrongylides sp. larvae (Dioctophymatidae) in arapaima fingerlings
      was also found (new host record); the larvae were inside swellings on the body
      surface.

PMID- 19391332
TI  - Female morphology of Philometra rubra (Nematoda: Philometridae), a parasite of
      the abdominal cavity of the striped sea-bass Morone saxatilis (Moronidae,
      Perciformes) in the USA.
AB  - The nematode Philometra rubra (Leidy, 1856) (Philometridae) is redescribed from
      subgravid females found in the abdominal cavity of the fish Morone saxatilis
      (Walbaum) from South Carolina, USA in November 2008. The species is characterized
      by the presence of 14 cephalic papillae arranged in two circles, a relatively
      long oesophagus with a distinct anterior inflation, and well-developed papilla
      like caudal projections. Cephalic papillae of the external circle differ from
      those in other congeners in that the dorso-lateral and ventro-lateral papillae
      are large, dome-shaped, whereas the dorso-dorsal and ventro-ventral papillae are
      small.

PMID- 19391333
TI  - Attachment of nymphal Rhipicephalus sanguineus (Acari: Ixodidae) to a human in an
      urban area followed by severe adverse reaction shortly before drop-off.
AB  - A case of attachment and complete engorgement of a Rhipicephalus sanguineus
      (Latreille, 1806) nymph on a woman with severe pain shortly before nymphal drop
      off is described. The pain continued for about 2 weeks after tick removal.
      Apparently, this is the first documented case of human adverse reaction developed
      at the very last stage of engorgement of nymphal R. sanguineus. The infestation
      most likely took place inside the enclosed household garden in the southern area
      of Jerusalem where the woman took care of the plants. The importance of immature
      R. sanguineus ticks in attacking humans is discussed.

PMID- 19391334
TI  - [Integrated multidisciplinary treatment of colorectal neoplasms].
AB  - In this retrospective study, the modality and advantages of the multidisciplinary
      diagnostic work-up and therapy regarding colorectal neoplasm were analysed. Over
      the period 2004-2008, 63 patients underwent multidisciplinary treatment for
      colorectal cancer. All patients underwent surgery (laparoscopic/open). Exeresis
      was supplemented by adjuvant chemotherapy in those cases beyond IIA stage; all
      cases of extraperitoneal rectal and anal canal neoplasms plus one case of
      carcinoma of the transverse colon, initially inoperable, underwent neoadjuvant
      radiotherapy plus chemotherapy. The treatment was initiated approximately 3 weeks
      after the diagnosis. Fifty-four percent of patients with colonic and upper rectal
      neoplasms were given adjuvant chemotherapy, starting around 4 weeks after
      surgery. Exeresis was performed in those patients with extraperitoneal rectal and
      anal canal neoplasms (12.7%) about 6-8 weeks after they had completed neoadjuvant
      therapy. At the end of the treatment, 76% of the overall total numbers of
      patients were in good condition (follow-up 4-50 months). The remaining 24%
      suffered recurrences about 13 months after the treatment for colonic and upper
      rectal neoplasm, and 8 1/2 months after treatment for extraperitoneal rectal/anal
      canal neoplasms. Seventy-five percent of the recurring cases underwent treatment
      again, with 50% success; the others are still undergoing treatment. The best
      therapeutic results were obtained by programmed integration of the various
      diagnostic-therapeutic steps according to an algorithm which we elaborated to
      evaluate all types of neoplasm at any stage of illness.

PMID- 19391335
TI  - [Gastrointestinal stromal tumour in emergency surgery].
AB  - Although rare, gastrointestinal stromal tumours (GIST) are the most common
      mesenchymal neoplasms of the gastrointestinal tract. We present our experience
      with the treatment of 8 patients affected by gastrointestinal stromal tumours of
      the ileum and colon. These cases were characterised by acute bleeding, intestinal
      obstruction or diffuse abdominal pain, and all of them underwent an emergency
      surgical treatment. We performed six partial resections of the ileum, one right
      hemicolectomy and one left hemicolectomy. Three patients died after surgical
      procedures for disease relapse, one died 10 years later due to other
      complications, and the others are still alive.

PMID- 19391336
TI  - [Role of anastomotic configuration in ileocolic resection for Crohn's disease].
AB  - Crohn's disease is characterised by a high incidence of perianastomotic
      recurrence after ileocolic resection. The influence of the anastomotic
      configuration on the incidence of reoperation was evaluated in patients
      undergoing resection for Crohn's disease. In our Institution, from 1993 to 2007,
      308 consecutive patients affected by ileocolic Crohn's disease were submitted to
      343 ileocolic resections or right colectomies. In 292 cases (85.1%), an
      antiperistaltic side-to-side (or functional end-to-end) anastomosis was
      performed, with an 80 mm linear stapler in 190 cases, a 100 mm linear stapler in
      79, and a hand-sewn anastomosis in 23. The other hand-sewn anastomotic
      configurations were: 30 (8.8%) side-to-side isoperistaltic, 15 (4.3%) end-to-side
      and 6 (1.8%) end-to-end. The overall morbidity was 7.3%, with two postoperative
      deaths (0.6%) with no significant differences between groups. There were 38
      overall recurrences (11%). In the side-to-side antiperistaltic group, the rate of
      recurrence was 8.2%, significantly lower than the recurrence rates observed in
      the other anastomoses (26.9%, p = 0.002), especially side-to-side isoperistaltic
      anastomosis (33.3%, p = 0.001). Early recurrences (< 1-year) were 2.6%, without
      significant differences between groups. There was a higher trend for end-to-end
      anastomosis (16.6%). In the side-to-side antiperistaltic group the morbidity was
      higher in the large mechanical anastomoses (100 mm length), but the recurrence
      rate was lower in this group as compared to the 80 mm anastomoses (1.2% vs.
      12.1%, p = 0.006). Our non-randomised study suggests a better trend for the wide
      side-to-side antiperistaltic technique in terms of recurrence rate. These
      observations need further investigation with randomised controlled trials to
      compare the different anastomotic procedures.

PMID- 19391337
TI  - Endoscopic gastrostomy for enteral nutrition in neurogenic dysphagia: Application
      of a nasogastric tube or percutaneous endoscopic gastrostomy.
AB  - Enteral nutrition can be administered via a nasogastric tube or, in selected
      patients, via a percutaneous endoscopic gastrostomy. In patients with neurogenic
      dysphagia, the choice of nutritional administration, and above all the timing,
      are crucial. Our aim was to retrospectively assess the impact of new guidelines
      for percutaneous endoscopic gastrostomy insertion adopted since January 2002 and
      compare them with our previous experience. From January 1992 to June 2007, 285
      gastrostomies (168 M, 117 F) were positioned in our institute. We analysed 232
      patients (139 M, 93 F) in whom a percutaneous endoscopic gastrostomy was applied
      for neurogenic dysphagia: Group A (from January 1992 to December 2001) consisting
      of 174 patients; Group B (from January 2002 to June 2007) consisting of 58
      patients. The percutaneous endoscopic gastrostomy was positioned in all the cases
      with neurogenic dysphagia after a period of not less than 3 weeks of nutrition by
      nasogastric tube. A total of 6 major complications (2.3 %) occurred, almost all
      in group A. The mortality rate (3 patients, 2%) correlated with the complications
      in group A. In cases of neurogenic dysphagia we believe that greater
      methodological rigour in the multidisciplinary decision-making process, and a
      period of about 6-8 weeks' nutrition by nasogastric tube after the acute
      neurological damage may be useful to ensure a better prognostic evaluation of the
      patient and hence of the indications for percutaneous endoscopic gastrostomy.

PMID- 19391338
TI  - [Role of laparoscopy in acute obstruction of the small bowel: personal experience
      and analysis of the literature].
AB  - Small bowel obstruction is caused by postoperative adhesions in most patients.
      The traditional surgical treatment has been laparotomy with adhesiolysis and
      possible resection of the ischaemic intestine. The laparoscopic approach has
      proved feasible but not without risks. We analysed our experience in the
      management of acute small bowel obstruction and then reviewed the literature in
      an attempt to identify the real role of laparoscopy. From January 2003 to June
      2008, 19 patients operated on for small bowel obstruction were identified. We
      evaluated our performance in terms of the aetiology of the obstruction, operative
      time, length of postoperative hospital stay, conversion rate, and major morbidity
      and mortality. Postoperative adhesions were responsible for the occlusion in 13
      cases; a single band was identified in 47% of patients (9 cases). Neoplastic
      disease (3 cases), a gallstone ileus, Crohn's disease and an internal hernia were
      the remaining cases. Laparoscopic treatment was only possible in 7 patients with
      single adhesions (77%), and a conversion was carried out in the remaining 12
      cases (63%), including "laparoscopy-assisted" cases (6 cases). The duration of
      the intervention (89 +/- 21 min vs 135 +/- 27.5 min) and postoperative
      hospitalisation (3.6 +/- 1 days vs 6.25 +/- 1.6 days) were in favour of the
      completely laparoscopic group as compared to the laparoscopy-assisted group. A
      case of postoperative peritonitis due to bowel perforation required a second
      intervention. With an appropriate selection of patients, confirming the high
      incidence of the single adhesions responsible for the occlusion and the resulting
      high success rate of laparoscopy, we believe that only an initial laparoscopic
      approach can help identify such favourable situations.

PMID- 19391339
TI  - Laparoscopic inguinal hernia repair: audit of our experience with laparoscopic
      trans-abdominal pro-peritoneal repair (TAPP).
AB  - Several laparoscopic procedures have successfully passed the stage of feasibility
      assessment and are currently under scrutiny with regard to indications.
      Laparoscopic repair of inguinal hernia is a typical example of such
      investigations, being mostly recommended only for bilateral and recurrent hernias
      at the moment. We performed an audit of our experience with 100 consecutive
      laparoscopic trans-abdominal pro-peritoneal repairs (T.A.P.P.) on 54 patients,
      mostly presenting with bilateral inguinal hernias over a period of 3 years.
      Operative time averaged 102 minutes for unilateral repairs and 123 minutes for
      bilateral repairs. When other procedures were added or a recurrent hernia was
      treated, operative time for bilateral repairs increased to 142 and 156 minutes,
      respectively. Prolene mesh size was 10 x 12 cm in most patients. Hospital stay
      averaged 3.7 days overall, averaging 3.3 and 3 days for bilateral and unilateral
      repairs. Added procedures lengthened the hospital stay to 4 and 10.6 days,
      respectively. In 85% of patients gas was passed on postoperative day 1.
      Postoperative morbidity consisted in 2 major (sizable haematoma) and 20 minor
      complications. Pain as estimated by a VAS scale was mild to low. Follow-up was
      obtained in 85% of patients and revealed only 2 recurrences, 1 incisional hernia,
      1 persistent swelling from a spiral tack, and 1 post-discharge bronchitis. In
      conclusion we believe laparoscopic inguinal hernia repair is the method of choice
      for treatment of bilateral and recurrent hernias and in selected cases of
      unilateral hernias.

PMID- 19391340
TI  - [Management of maxillofacial injuries in an emergency unit: our experience].
AB  - Maxillofacial injuries are relatively frequent. These may be complicated by
      cranioencephalic injuries or large facial wounds. We report our experience with
      the initial management of these lesions in an emergency unit setting. In 2007, we
      observed 105 patients with maxillofacial injuries. Maxillofacial injuries were
      associated with cranio-encephalic injuries in 69 patients (65.7%) and with
      polytrauma in 31(29.5%), while in 5 cases (4.8%) they were isolated. The main
      causes of trauma were motorcycle accidents (60%). All patients were treated in
      accordance with the Advanced Trauma Life Support guidelines and assessed by
      computed tomography. No mortality was observed after diagnosis in the emergency
      unit or in the month following the trauma. Seventy-seven patients (73.3%) were
      admitted and 28 (26.7%) were treated and discharged. Accurate diagnosis and
      appropriate initial management yield good clinical outcomes with functional
      restoration and fewer aesthetic complications.

PMID- 19391341
TI  - Abdominal aortic endograft infection: report of two cases and review of the
      literature.
AB  - Endovascular prosthesis infection after exclusion of an abdominal aortic aneurysm
      is a rare, dramatic event and its diagnosis and treatment are extremely complex.
      This particular complication has been less well explored in the literature than
      others such as endoleaks, migration or stent rupture. The incidence of aorto
      iliac stent-graft infection is almost 0.7%, while the infection rate in open
      surgery varies from 0.6% to 3%. Moreover, the infection can be early when it
      arises within 4 months of the implant or late when it arises after 4 months.
      Since 1991 only 94 cases of endograft infections have been reported in the world
      literature, to which our two cases need to be added, making a total of 96 cases.
      The first of our patients was diagnosed with an early infection that was
      successfully treated by explanting the infected graft followed by aortic
      reconstruction with a homograft. Six months after the operation the patient died
      of cardiac failure. The second case was a late infection which developed 8 years
      after the first intervention in a patient with chronic renal failure treated with
      dialytic therapy. After aneurysmectomy and stent-graft removal, a bifurcated
      dacron silver graft was implanted. The patient died of cardiogenic shock 40 days
      after surgery. The surgical treatment of this serious complication is associated
      with high perioperative morbidity and mortality rates and requires very careful
      planning of the operation.

PMID- 19391342
TI  - [Coleman lipofilling: experience of an Italian group and review of the
      literature].
AB  - Although the first operation of reconstructive breast surgery dates back to the
      end of the nineteenth century, it was only in the last decade of the twentieth
      century that lipofilling became widely adopted in the management of diseases of
      the breast. The Coleman technique involves taking a sample of fat from the
      regions of the body where it is largely present (abdomen, trochanter region,
      groin, knee), followed by centrifugation and the grafting of the fat cells thus
      purified. In 1987 the American Society of Plastic and Reconstructive Surgery
      banned the diffusion of this procedure because it was considered of little
      benefit for both aesthetic and oncological purposes. From January 2005 to May
      2007, 17 patients underwent lipofilling according to the Coleman technique at the
      Operative Unit of General Surgery of the "San Giuseppe Moscati" Hospital in
      Avellino. Previously, 15 (88%) of the 17 women had received reconstructive breast
      surgery with a prosthesis after a Madden total mastectomy. As regards the other 2
      patients, when admitted to hospital, one (5.9%) presented a pectum excavatum and
      the other (5.9%) a congenital depression of the temporal bone. No important
      complications were observed in the postoperative course. At a distance of 6 and
      12 months after the injection, follow-up monitoring revealed that the loss of
      substance in the grafted adipose tissue was about 53%. In conclusion,
      reconstructive breast surgery should always be attempted after radical surgery.
      The multidisciplinary cooperation of radiologists, surgeons, anatomical
      pathologists and psychologists, in our opinion, avoids the danger of poor
      aesthetic results and the risk of underestimating a possible tumour relapse.

PMID- 19391343
TI  - [Use of an evaluation score for rectal mucosal prolapse].
AB  - Rectal mucosal prolapse is characterised by the protrusion of the mucosa alone in
      the rectal lumen. The authors, after an experience conducted in ambulatory
      patients, have produced a score to classify the extent of rectal mucosal prolapse
      based on evaluation of qualitative and quantitative factors that should help in
      the correct management of proctological patients. A total of 30 patients with
      proctological symptoms during outpatient visits were submitted to a minimally
      invasive test in comparison to the traditional ones, using a simple gauze plug
      connected to the end of a suture thread, inserted in the rectal lumen and removed
      via the anus. The score designed by the authors made it possible to classify
      96.6% of patients accurately. In 4 patients the score was equal to zero. In 12
      patients there was a mucosal prolapse of less than 25% with a reduction score
      equal to 2.4 and therefore these were treated with a single rubber ligature (7
      patients with classes a and b) and 5 patients were treated with the transfixed
      stitch technique (TST) (class c). In 10 patients a 50% mucosal prolapse of the
      anal circumference and a mean reduction score of 5.6 were found. In 5 of these
      patients (classes a and b) it was possible to perform a multiple ligature while
      the other 5 (class c) were treated with TST. In 3 patients a prolapse ranging
      from 50 to 75% with a mean reduction index of 8.1 was found. The therapeutic
      procedure preferred for these patients was TST. In one patient a circumferential
      prolapse was diagnosed with a reduction score of 11 treated with Longo's surgical
      technique. The mucosal prolapse score seems to be useful to stratify patients
      more precisely in the choice of surgical intervention and during follow-up. The
      plug test is a minimally invasive test, useful for the application of the rectal
      mucosal prolapse score.

PMID- 19391344
TI  - [Laparoscopic wedge resection for gastrointestinal stromal tumour: a case
      report].
AB  - Surgical resection is the main and most effective treatment for gastrointestinal
      stromal tumours (GISTs) and for all benign gastric tumours. All such tumours
      should be approached with the intention of performing complete en bloc removal of
      the tumour, achieving microscopically tumour-free pathological resection margins.
      More extensive surgery fails to guarantee better results over time. Consequently,
      wedge resection of the stomach ensures adequate therapy. Our personal experience
      with laparoscopic wedge resection for a gastrointestinal stromal tumour is
      described, demonstrating equivalent efficacy, greater safety, and applicability,
      and better postoperative results with this surgical approach.

PMID- 19391345
TI  - [Ileal intussusception due to a voluminous inflammatory fibroid polyp. A case
      report and review of the literature].
AB  - An inflammatory fibroid polyp is a rare benign submucosal lesion frequently
      located in the gastric antrum but it may be found anywhere in the
      gastrointestinal tract with maximal incidence in the fifth and sixth decades of
      life. The main histological characteristics are diffuse inflammatory infiltrate
      with eosinophils, high vascularisation and a myofibroblastic component. Its
      localisation in the small bowel can cause intestinal invagination in adults, a
      condition, that occurs most frequently in childhood where, however, it is
      generally not related to a pathological lesion. The diagnosis may often be
      delayed because of its non-specific symptoms and most cases are diagnosed at
      emergency laparotomy, although CT scans can furnish useful preoperative
      information. In the majority of cases, the treatment of choice is surgical
      resection. Reduction performed prior to resection proves controversial in
      patients with colic intussusception because of the high incidence of malignancy.
      We report a case of a 37-year-old man who had undergone emergency surgery for
      acute ileum intussusception associated with a voluminous inflammatory fibroid
      polyp. The case described emphasises that patients with bowel obstruction pose a
      complex and difficult challenge to surgeons as regards the choice of the correct
      diagnostic work-up and optimal therapeutic management.

PMID- 19391346
TI  - Gastro-oesophageal reflux and "epileptic" attacks: casually associated or
      related? Efficiency of antireflux surgery: a case report.
AB  - Although a possible link between gastro-oesophageal reflux disease (GORD) and
      obstructive sleeping apnoea has already been reported in the literature, there
      has never been any suggestion of an association with epilepsy, and epileptic
      attacks have not so far been included among gastro-oesophageal reflux disease
      symptoms. We report the case of a patient with gastro-oesophageal reflux disease
      associated with a sliding hiatus hernia, a short oesophagus and oesophagitis, who
      for the last ten years had not only presented the typical symptoms of
      gastrooesophageal reflux, but also symptoms of obstructive sleep apnoea and
      epileptic-like attacks occurring occasionally and only during sleep. Partial
      posterior fundoplication was performed and considerably reduced the reflux
      symptoms, and in addition brought about a drastic decrease in the number of
      epileptic-like attacks. Our case suggests that epileptic-like episodes in
      patients with obstructive sleeping apnoea may well be linked to the simultaneous
      presence of GORD associated with hiatus hernia, and surgical treatment of GORD
      may bring about an improvement of the neurological problems.

PMID- 19391347
TI  - [Reconstruction of the gastrointestinal tract in the absence of the oesophagus,
      stomach and colon, with preservation of the larynx].
AB  - The authors report a case of reconstruction of the gastrointestinal tract in a
      young woman of 36 years of age who, after ingesting muriatic acid, and after a
      series of consecutive operations found herself without an oesophagus (from the
      hypopharynx) stomach and colon. She was fed with a jejunostomy and had a large
      pharyngostomy to prevent sialorrhoea. After one year, the patient manifested the
      need to resume eating by mouth. The problem was serious due both to the
      anastomosis above the level of the larynx and the very long period of
      rehabilitation. The technical problem included the need to avoid the thoracic
      cavity due to the previous empyema, and thus to bring a viable jejunal loop up to
      the neck in a subject already operated on four times. The solution was a Roux
      loop at the level of the 4th-5th jejunal arcade brought to the neck via a
      subcutaneous presternal route and anastomised in a supraglottic location at the
      level of the right pyriform sinus. The viability of the loop was guaranteed by an
      arterial shunt with a branch of the mesenteric artery by means of a segment of
      saphenous vein and a venous shunt over the right internal jugular vein to
      guarantee venous flow. The pharyngo-jejunal anastomosis was done with a 21 mm
      circular stapler with a rotary head after a partial parietal resection of the
      laryngeal cartilage and under the protection of a provisional tracheostomy. After
      4 months' treatment, partly in intensive care and partly in a rehabilitation
      centre with logopaedic assistance, the tracheal cannula could be removed and the
      patient is now able to eat by mouth with normal phonation.

PMID- 19391348
TI  - [Benign retroperitoneal schwannoma: a case report and review of the literature].
AB  - Retroperitoneal schwannoma is a very rare benign tumour that accounts for only a
      small percentage of retroperitoneal tumours. The preoperative diagnosis is
      difficult and the only treatment is complete surgical excision. The authors
      report their experience with a case of a voluminous retroperitoneal mass in a 42
      year- old male patient, incidentally discovered during a diagnostic search for a
      blunt abdominal trauma. Because of the unclear origin of this mass, the patient
      underwent periodic radiological and ultrasonographic examinations. Three years
      later, owing to a slight increase in this mass and vague abdominal discomfort
      reported by the patient, surgical excision was performed. Histological
      examination of the surgical specimen revealed an "ancient schwannoma". The
      patient is alive and well and has had no recurrence in the twenty months since
      surgery. The authors, after a short discussion of the subject, go on to examine
      the diagnostic and therapeutic treatments of this rare benign neoplasm, which
      always arouses lively clinical and scientific interest.

PMID- 19391349
TI  - Retroperitoneal schwannoma unusually presenting as severe constipation.
AB  - Retroperitoneal schwannomas are rare tumours originating from Schwann cells of
      peripheral nerve sheaths. Their clinical presentation is often delayed as they
      grow to a large size in a non-restrictive space, such as the retroperitoneum,
      before any clear symptomatology is manifested. Furthermore, the symptoms may
      mimic different diseases and be aspecific. The preoperative diagnosis is often
      unclear as no pathognomonic radiological features are known. Fine needle biopsy
      is not diagnostic due to tumour cell pleomorphism. We report the case of a 51
      year-old woman presenting with unusual symptoms such as severe constipation,
      bowel distension, excess flatus, postprandial fullness and abdominal pain due to
      left colon compression by a large retroperitoneal tumour. A complete resection of
      the mass combined with sparing of the surrounding tissues was carried out through
      a midline laparotomy. Microscopic evaluation and immunohistochemistry documented
      a benign retroperitoneal schwannoma. Postoperatively, complete resolution of
      abdominal symptoms and no major complications were observed. At 28 months' follow
      up no local recurrence was found. To the best of our knowledge, this is a rare
      case of retroperitoneal schwannoma with definite abdominal symptoms and with
      sudden onset of severe constipation.

PMID- 19391350
TI  - [Surgical management of schwannoma of biliary tract].
AB  - A borderline Schwann cell tumour with common bile duct compression and jaundice
      is extremely rare. This paper presents the first report in the Italian literature
      of a hepatojejunostomy for a symptomatic lesion midway between benign and
      malignant.

PMID- 19391351
TI  - [Rupture of the pancreatic isthmus due to blunt abdominal trauma].
AB  - The authors report a case of a grade III pancreatic injury resulting from a blunt
      abdominal trauma, referred to our department for observation and treated with
      distal splenopancreatectomy. Pancreatic traumas account for approximately 3-5% of
      blunt abdominal injuries. In cases of isolated pancreatic injuries failure to
      recognise injury to the Wirsung duct is the main cause of morbidity and
      mortality. Spiral CT with contrast medium is the standard investigation in
      haemodynamically stable traumatised patients, with a sensitivity of approximately
      90% in the most recent series. However, at least initially, the extent of the
      pancreatic damage is not proportional to the severity of the clinical and
      instrumental picture. The patients need to be continuously and carefully
      monitored and, in the case of suspected pancreatic injury, the imaging study
      should be repeated 12-24 hours after the trauma. In case of doubt, ERCP provides
      detailed information on the condition of the Wirsung duct and, in selected cases,
      may play a therapeutic role through the positioning of an intraductal prosthesis.
      The surgical management of blunt pancreatic trauma should be individualised
      depending on the site and severity of the injury, the interval elapsing after the
      trauma and the presence of associated injuries.

PMID- 19391352
TI  - Perineal hernia: a case of outlet dysfunction.
AB  - This article describes and discusses a successfully treated case of a primary
      posterior perineal hernia which is a rare cause of outlet dysfunction. A 46-year
      old female patient had a 6 cm left para-anal protrusion and a 7-year history of
      outlet dysfunction. The perineal hernia orifice was closed via an abdominal
      approach using both a polypropylene mesh and a Parietex Composite Net. A
      rectopexy to the promontory of the sacrum was then performed. Moreover, after 6
      months' follow-up, the patient presented a sense of incomplete evacuation and
      underwent a prolassectomy to treat a hidden rectal prolapse. This clinical case
      shows that the surgical treatment of a pelvic pathology can be successful for the
      correction of a serious functional defect such as outlet dysfunction.

PMID- 19391353
TI  - Anorectal and perineal injury due to a personal watercraft accident: case report
      and review of the literature.
AB  - We report a case of a 28-year-old male with an anorectal trauma sustained while
      he was riding as a passenger on a personal watercraft. Management, treatment and
      outcome of the case are described. A brief analysis of the literature is
      discussed.

PMID- 19391354
TI  - Breaking new ground: the story of Dagmar Berne.
AB  - In 1885 a young country girl enrolled in medicine at Sydney University. She was
      the first woman in Australia to enroll in a medical school. The medical school at
      this time was heavily influenced by academics who had graduated from the
      University of Edinburgh. At one point in her medical education she experienced
      difficulties with her examinations, the reasons for which are a point for debate.
      Under the mentorship of a famous British female medical practitioner who was
      visiting Australia at the time, she continued her studies in the United Kingdom.
      Here she was successful and returned to practice in New South Wales in 1895. Her
      experience of medical education was not without suffering. This young woman
      became part of an international group of women who at the time were trying to
      break into a field dominated by men.

PMID- 19391355
TI  - A quest for identity, authority, and status: the development of paediatrics in
      Australia.
AB  - In Europe and the United States paediatrics was well entrenched by the end of the
      nineteenth century; whereas in Australia the specialty only attained legitimacy)
      by the end of the twentieth. Here paediatricians experienced difficulties in
      convincing the medical profession and society that children were different to
      adults and therefore required special care. In seeking a clear identity as
      specialists for children they were reluctant to distance themselves from their
      origins in general, predominantly adult, medicine, which, until the 1970s,
      followed British ideologies in opposing specialisation. There were also local
      socio-economic factors, adverse market forces, and competition in the field of
      child health. Even when the problems were largely overcome and new scientific
      knowledge gave paediatricians authority and status, they were slow to establish
      an effective professional association. Eventually, however, they achieved their
      aims with the creation, in 1998, of the Paediatric Division of the Royal
      Australasian College of Physicians.

PMID- 19391357
TI  - Indigenous health in a global frame: from community development to human rights.
AB  - This essay explores the shift from 'human rights' to community development' in
      the framing of Koori (or Indigenous) health policy research at the University of
      Melbourne in the 1990s. It provides an overview of the recent history of rights
      based discourses in international health, contrasting cosmopolitan claims of
      rights with older civic reference points for health intervention: such as
      'citizenship' and 'community development.' In particular it considers the
      relations of the conjunction 'health and human rights' to the global emergence
      during the past twenty years of nongovernmental organisations and their challenge
      to the power of the nation-state. This account draws heavily on the author's
      observation of the institutionalisation of rights discourses in health research
      programs at Melbourne and Harvard, vantage points that provide at best a partial
      perspective, but one that may nonetheless reveal some salient historical
      features.

PMID- 19391356
TI  - Suicide research before Durkheim.
AB  - The casual reader could be forgiven for assuming that there had been little
      systematic research on suicide before the work of the French sociologist, Emile
      Durkheim, published in 1897. This historical review demonstrates that there had
      been extensive studies in the preceding centuries, addressing not only the
      importance of social factors, but also those factors which are now subsumed in
      the medical model. In fact, some earlier reviews can now be seen as more balanced
      and comprehensive than that of Durkheim. In the twentieth century. the
      predominant focus of suicide research was on the importance of psychosocial
      factors, a focus which was undoubtedly a legacy of the influential work of
      Durkheim. Indeed, in 1971 Alvin Alvarez stated that the study of suicide had
      become the subject of intensive scientific research. The change began in 1897
      with the publication of Emile Durkheim's classic Suicide: A Study in Sociology,
      and more recently Alexander Murray noted that, if the study of suicide had its
      own era it would divide into two ages, before and after that book ... Le Suicide
      ... which, more than any other, established its subject as a specialization.
      Therefore it is not unexpected that many believe that there had not been any
      substantial suicide research before Durkheim, let alone any which had addressed
      illness and biological factors and their inter-relationship with society.

PMID- 19391358
TI  - The formative years of nuclear medicine in Victoria.
AB  - Nuclear medicine is defined, and its development as a specialty in Victoria from
      the 1940s to the 1990s recorded, with the developing use of radioisotopes in
      investigations and treatment. The combined efforts of medical, scientific, and
      technical personnel is emphasised, together with the advances in instrumentation
      and radiopharmacy. The formation of the Australian and New Zealand Society for
      Nuclear Medicine is outlined, together with the training of medical and technical
      personnel, and some of the political issues in the establishment of the
      specialty.

PMID- 19391359
TI  - [Beyond Weimar Culture--the significance of the Forman thesis for a cultural
      approach to the history of science].
AB  - '"Forman thesis', published in 1971, argued for a historical linkage among the
      intellectual atmosphere of Weimar Germany, popular revolts against determinism
      and materialism, and the creation of the revolutionary new theory of quantum
      mechanics. Paul Forman's long essay on "Weimar Culture" has shaped research
      agendas in numerous fields, from the history and philosophy of physics to German
      history to the sociology of scientific knowledge. Despite its status as a classic
      and its transformative effect, Weimar Culture has always inspired as much
      critique as assent. In particular in the history of science, cohorts of students
      and two generations of scholars have debated the Forman thesis as a conceptual
      tool for linking scientific change with cultural processes. The Forman thesis
      raises critical questions for both the ongoing debates over cultural approaches
      to the history of science and the burgeoning newer scholarship on physics in and
      beyond Weimar Germany. Exploring these implications has been the aim of a
      transnational project of the three authors of this article which sheds some light
      on these debates and briefly introduces the following papers of this special
      issue devoted to Paul Forman and his seminal works in the history of science.

PMID- 19391360
TI  - The fin de siecle thesis.
AB  - This paper examines the relations between John Heilbron's argument that fin de
      siecle physicists adjusted the image and substance of their discipline to
      cultural concerns, and Paul Forman's approach to acau-sality in the Weimar
      period. In addition to their focus on representation rather than truth, adherents
      of the "descriptionist" epistemologies that Heilbron identified also promoted an
      emphasis on method, statistical rather than causal explanations, historical
      understandings of epistemology, and stressed the relations between physics and
      other disciplines. Their views provide an intellectual context--within the
      physics discipline--for at least some part of what Forman had described as a
      capitulation to the hostile social environment expressed in Oswald Spengler's Der
      Untergang des Abendlandes.

PMID- 19391361
TI  - [Cosmos, coral and cultural milieu. The significance of the popular science
      connection in the late German Empire and the Weimar Republic].
AB  - This paper discusses the role of popular science communication for the 'cultural
      milieu' or more generally the 'environment' of scientists and science in Germany
      between c. 1900 and 1933 in the sense of Paul Forman. On the rich basis of
      diverse journals aiming at a differentiated public the discourse on atomic
      physics is sketched. Since the thesis of a general hostility towards atomic
      physics in particular and science in general cannot be accredited the question
      arises how widespread and in which sense a crisis of science was discussed in the
      Weimar years.

PMID- 19391362
TI  - Hostile environmental intellectuals? Critiques and counter-critiques of science
      and technology in West Germany after 1945.
AB  - Paul Forman, in his work on physics in Weimar Germany, advanced the thesis that
      an irrationalist current within German intellectual history was then suddenly
      exacerbated in a context of defeat and political crisis. After World War II,
      Germany's situation was if any thing even more catastrophic; nevertheless, a
      comparable climate of irrationalism arose only in a limited way. The collapse of
      National Socialism was, in effect, sufficiently explicable on rational grounds to
      resort to a philosophical fatalism. F. G. Junger, as a possible exception, put
      forward a theory of autonomous, demonic technology as an explanation; many
      cultural critics of the time, however, found these views unrealistic and favored
      an integration of technical and humanistic approaches. Moreover, even a new wave
      of (sometimes apocalyptic) literature of environmental crisis focused on specific
      scientifically analyses rather than a diffuse cultural pessimism.

PMID- 19391363
TI  - Kantian philosophy and the human sciences.

PMID- 19391364
TI  - Kant's transcendental and empirical psychology of cognition.
AB  - One of the perennially intriguing questions regarding Kant's approach to the
      human sciences is the relation between his 'transcendental psychology' and
      empirical cognitive psychology. In this paper I compare his analysis of the a
      priori conditions of human cognition in the Critique of pure reason with his
      empirical account of the human cognitive faculties in his Anthropology from a
      pragmatic point of view. In comparing his approach to self-consciousness,
      sensibility, imagination, and understanding in these two works, I argue that Kant
      distinguishes between the transcendental and empirical aspects of the human
      cognitive faculties, and regards the transcendental functions as configuring the
      empirical faculties of human consciousness, or as giving them the structure that
      they require to become faculties of cognition. I then show that the cognitive
      faculties of human beings may vary in their empirical operation, even while they
      are configured by the same transcendental structure. Finally, I characterize
      Kant's transcendental psychology in the first Critique as an account of the
      faculties that are required for a mind to be an agent or subject of cognition,
      corresponding to his account of the conditions that are required universally and
      necessarily for something to be an object of cognition.

PMID- 19391365
TI  - Empirical psychology, common sense, and Kant's empirical markers for moral
      responsibility.
AB  - This paper explains the empirical markers by which Kant thinks that one can
      identify moral responsibility. After explaining the problem of discerning such
      markers within a Kantian framework I briefly explain Kant's empirical psychology.
      I then argue that Kant's empirical markers for moral responsibility--linked to
      higher faculties of cognition--are not sufficient conditions for moral
      responsibility, primarily because they are empirical characteristics subject to
      natural laws. Next. I argue that these markers are not necessary conditions of
      moral responsibility. Given Kant's transcendental idealism, even an entity that
      lacks these markers could be free and morally responsible, although as a matter
      of fact Kant thinks that none are. Given that they are neither necessary nor
      sufficient conditions, I discuss the status of Kant's claim that higher faculties
      are empirical markers of moral responsibility. Drawing on connections between
      Kant's ethical theory and 'common rational cognition' (4:393), I suggest that
      Kant's theory of empirical markers can be traced to ordinary common sense beliefs
      about responsibility. This suggestion helps explain both why empirical markers
      are important and what the limits of empirical psychology are within Kant's
      account of moral responsibility.

PMID- 19391366
TI  - The psychology of Kant's aesthetics.
AB  - Contrary to both his own intentions and the views of both older and more recent
      commentators. I argue that Kant's aesthetics remains within the confines of
      eighteenth-century aesthetics as a branch of empirical psychology, as it was then
      practiced. Kant established a plausible connection between aesthetic experience
      and judgment on the one hand and cognition in general on the other, through his
      explanatory concept of the free play of our cognitive powers. However, there is
      nothing distinctly 'a priori' or 'transcendental' in his claim that this state of
      mind is what causes our pleasure in beauty or other aesthetic properties. Nor did
      Kant establish a genuinely a priori or transcendental principle that all human
      beings have the same disposition to experience a free play of their cognitive
      powers, let alone in response to the same objects. This failure, however, in no
      way limits the continuing significance of Kant's aesthetic theory.

PMID- 19391367
TI  - Why did Kant reject physiological explanations in his anthropology?
AB  - One of Kant's central tenets concerning the human sciences is the claim that one
      need not, and should not, use a physiological vocabulary if one studies human
      cognitions, feelings, desires, and actions from the point of view of his
      'pragmatic' anthropology. The claim is well known, but the arguments Kant
      advances for it have not been closely discussed. I argue against misguided
      interpretations of the claim, and I present his actual reasons in favor of it.
      Contemporary critics of a 'physiological anthropology' reject physiological
      explanations of mental states as more or less epistemologically dubious. Kant
      does not favor such ignorance claims--and this is for the good, since none of
      these claims was sufficiently justified at that time. Instead, he develops an
      original irrelevance thesis concerning the empirical knowledge of the
      physiological basis of the mind. His arguments for this claim derive from his
      original and, up to now, little understood criticism of a certain conception of
      pragmatic history, related to his anthropological insights concerning our ability
      to create new rules of action, the social dynamics of human action, and the
      relative inconstancy of human nature. The irrelevance thesis also changes his
      views of the goal and methodology of anthropology. Kant thereby argues for a
      distinctive approach in quest for a general 'science of man'.

PMID- 19391368
TI  - Kant's answer to the question 'what is man?' and its implications for
      anthropology.
AB  - This paper examines Kant's anthropological project and its relationship to his
      conception of 'man' in order to show that Kant's answer to the question 'what is
      man?' entails a decisive re-evaluation of traditional conceptions of human
      nature. I argue that Kant redirects the question 'what is man?' away from
      defining man in terms of what he is, and towards defining him in terms of what he
      does, in particular through the distinction between three levels of what I will
      call 'man's praxis': the levels of technicality, prudence, and morality. As soon
      as man is understood in terms of what he makes of himself rather than in terms of
      what he is, two crucial issues arise: what is the purpose of his making? And how
      can he reach this destination? My claim is that whilst the first question is
      answered by ethics and a doctrine of prudence, the second question is answered by
      anthropology. In this sense, anthropology plays the crucial role of identifying
      the worldly helps and hindrances to the realisation of man's purposes--and this
      is the reason why it should be understood as a 'pragmatic' discipline.

PMID- 19391369
TI  - Anthropology from a Kantian point of view: toward a cosmopolitan conception of
      human nature.
AB  - Anthropology was a new field of study when Kant first began lecturing on it in
      1772, and Kant himself was the first academic to teach regular courses in this
      area. As is well known, his own approach to anthropology is self-described as
      'pragmatic', and Kant's pragmatic anthropology differs markedly from the
      anthropologies that other early contributors to the new discipline were
      advocating. In this essay I focus on a fundamental feature of Kant's anthropology
      that has been under-appreciated in previous discussions; namely, the particular
      conception of human nature that he believes anthropology, when pursued properly,
      leads to. I call this conception a cosmopolitan conception of human nature. In
      addition to establishing the central importance of this idea for Kant's project
      in anthropology, I also try in this essay to unravel some of its ambiguities and
      tensions as well as to highlight its underlying moral motives. The cosmopolitan
      conception of human nature that is central to Kant's anthropology is a further
      indication of the significance of his anthropology for ethics.

PMID- 19391370
TI  - Kant on historiography and the use of regulative ideas.
AB  - In this paper, I examine Kant's methodological remarks in the 'Idea for a
      universal history' against the background of the Critique of pure reason. I argue
      that Kant's approach to the function of regulative ideas of human history as a
      whole may still be fruitful. This approach allows for regulative ideas that are
      grand in scope, but modest and fallibilistic in their epistemic status. Kant's
      methodological analysis should be distinguished from the specific teleological
      model of history he developed on its basis, however, because this model can no
      longer be appropriated for current purposes.

PMID- 19391371
TI  - Historical trends and human futures.
AB  - Kant's essay Idea for a universal history with a cosmopolitan purpose differs in
      deep ways from standard Enlightenment views of human history. Although he agrees
      with many contemporaries that unsocial sociability can drive human progress, he
      argues that we know too little about the trends of history to offer either
      metaphysical defence or empirical vindication of the perfectibility of man or the
      inevitability of progress. However, as freely acting beings we can contribute to
      a better future, so have grounds for committing ourselves to human progress even
      if we cannot guarantee or know that it will continue indefinitely. As Kant sees,
      it, human progress is better seen as a practical assumption--an Idea of Reason-
      than as a theoretical claim.

PMID- 19391372
TI  - A text of two titles: Kant's 'A renewed attempt to answer the question: "is the
      human race continually improving"?
AB  - The essay, 'A renewed attempt to answer the question: "Is the human race
      continually improving?"' appeared as Part II of Kant's 1798 publication, The
      conflict of the faculties, where it was subordinated under a second title: 'The
      conflict of the philosophy faculty with the faculty of law'. How did this new
      situation (and title) affects the meaning of the essay? My argument considers
      first, the conflict of the faculty of philosophy with the faculty of law; second,
      the earlier philosophy of history Kant had developed; and, finally, the revision
      of this position in 'A renewed attempt'. The situation of his argument in the
      contest between the philosophical and the legal faculties points to other veins
      of argumentation in Kant's political theory, particularly his appeal to a
      principle of publicity, but they hardly achieve the theoretical clarity or the
      systematic centrality they should command. They are displaced in the quest for
      prediction of the future history of mankind. The question of human progress
      exceeds the frame of the coordination of the university, and the main question
      must remain: what was new in Kant's approach to the question of human progress,
      and was it in fact an enhancement of his philosophy of history? In those terms,
      'A renewed attempt' must be regarded a distinct failure. Its innovations prove
      problematic. Its retreats and equivocations, moreover, threaten to undermine the
      grander vision of Kant's philosophical history and his political theory,
      entangling them in an unacceptably theological recourse.

PMID- 19391373
TI  - Kant and the development of the human and cultural sciences.
AB  - Starting with Kant's doubts about psychology as a natural science capable of
      explaining human behavior, several alternative attempts to conceive of human
      life, culture and history are examined. Kant proposes an anthropology that will
      be a commonly useful human science rather than a universally valid natural
      science. This anthropology relates to philosophy as a mode of world-cognition.
      Special attention is given to how Kant's theory of right can help define our
      appropriate place in a communal world. The different ways in which Wilhelm
      Dilthey and Hermann Cohen respond to Kant's idea of legitimate appropriation are
      also considered. The various tasks that descriptive elucidation, explanation,
      reflective understanding, characterization and interpretation can perform for the
      human and cultural sciences are examined throughout the essay.

PMID- 19391374
TI  - Historicism and neo-Kantianism.
AB  - This article treats the conflict between historicism and neo-Kantianism in the
      late nineteenth century by a careful examination of the writings of Wilhelm
      Windelband, the leader of the Southwestern neo-Kantians. Historicism was a
      profound challenge to the fundamental principles of Kant's philosophy because it
      seemed to imply that there are no universal and necessary principles of science,
      ethics or aesthetics. Since all such principles are determined by their social
      and historical context, they differ with each culture and epoch. Windelband
      attempted to respond to the challenge of this relativism by either broadening
      Kantian principles, so that they could accommodate the results of historicism, or
      by reformulating Kantian principles, so that they were impregnable to historical
      change. The article examines both aspects of Windelband's strategy in some
      detail, noting the many changes and different formulations in his views. A final
      section considers some of the difficulties of Windelband's strategy and concludes
      that, despite its heroic efforts, it was a failure.

PMID- 19391375
TI  - The Dao of human cloning: utopian/dystopian hype in the British press and popular
      films.
AB  - The issue of human cloning has featured in the national science policy agendas in
      both the United States and the United Kingdom since the announcement in 1997 of
      Dolly the cloned sheep's birth in Scotland. Such news stories suggesting the
      imminent cloning of humans have inspired fictional entertainment media over the
      years, including numerous popular films. Study 1 examines elite British press
      coverage of human cloning from 1997 to 2004 (n = 857). Study 2 focuses on five
      human cloning films released between 1978 and 2003. Two sharply divergent
      discourses emerged from these data. Unqualified hope and habitually hyped claims
      of future cures permeated the press discourse. In contrast, the films constructed
      human cloning as an inherently dangerous technology often wielded by hubristic
      scientists in the tradition of Frankenstein. Both the predominately positive hype
      in the broadsheet press and the largely negative hype in the films indicate an
      impoverished and "thin" public debate on the issue of human cloning.

PMID- 19391376
TI  - Reframing nuclear power in the UK energy debate: nuclear power, climate change
      mitigation and radioactive waste.
AB  - In the past decade, human influence on the climate through increased use of
      fossil fuels has become widely acknowledged as one of the most pressing issues
      for the global community. For the United Kingdom, we suggest that these concerns
      have increasingly become manifest in a new strand of political debate around
      energy policy, which reframes nuclear power as part of the solution to the need
      for low-carbon energy options. A mixed-methods analysis of citizen views of
      climate change and radioactive waste is presented, integrating focus group data
      and a nationally representative survey. The data allow us to explore how UK
      citizens might now and in the future interpret and make sense of this new framing
      of nuclear power--which ultimately centers on a risk-risk trade-off scenario. We
      use the term "reluctant acceptance" to describe how, in complex ways, many focus
      group participants discursively re-negotiated their position on nuclear energy
      when it was positioned alongside climate change. In the concluding section of the
      paper, we reflect on the societal implications of the emerging discourse of new
      nuclear build as a means of delivering climate change mitigation and set an
      agenda for future research regarding the (re)framing of the nuclear energy debate
      in the UK and beyond.

PMID- 19391377
TI  - Social identities and risk: expert and lay imaginations on pesticide use.
AB  - Expert-based environmental and health risk regulation is widely believed to
      suffer from a lack of public understanding and legitimacy. On controversial
      issues such as genetically modified organisms and food-related chemicals, a "lay
      expert discrepancy" in the assessment of risks is clearly visible. In this
      article, we analyze the relationship between scientific experts and ordinary lay
      citizens in the context of risks from pesticide usage in Denmark. Drawing on
      concepts from the "sociology of scientific knowledge" (SSK), we contend that
      differences in risk perception must be understood at the level of social
      identities. On the basis of qualitative interviews with citizens and experts,
      respectively, we focus on the multiple ways in which identities come to be
      employed in actors' risk accounts. Empirically, we identify salient
      characteristics of "typical" imagined experts and lay-people, while arguing that
      these conceptions vary identifiably in-between four groups of citizens and
      experts. On the basis of our findings, some implications for bridging the lay
      expert discrepancy on risk issues are sketched out.

PMID- 19391378
TI  - Making sense scientific claims in advertising. A study of scientifically aware
      consumers.
AB  - Evidence that science is becoming increasingly embedded in culture comes from the
      proliferation of discourses of ethical consumption, sustainability, and
      environmental awareness. Al Gore's recent award, along with UN's Inter
      governmental Panel on Climate Change (IPCC) of the Nobel peace prize-- provided a
      recent high profile linking of consumption and science. It is not clear to what
      extent the public at large engages in evaluating the scientific merits of the
      arguments about the link between human consumption and global environmental
      catastrophes. But on a local scale, we are routinely required to evaluate,
      scientific and pseudoscientific claims in advertising. Since advertising is used
      to sell products, the discourse of scientifically framed claims is being used to
      persuade consumers of the benefits of these products. In the case of functional
      foods and cosmetics, such statements are deployed to promote the health benefits
      and effectiveness of their products. This exploratory study examines the views of
      British consumers about the scientific and pseudoscientific claims made in
      advertisements for foods, with particular reference to functional foods, and
      cosmetics. The participants in the study all worked in scientific environments,
      though they were not all scientists. The study found that scientific arguments
      that were congruent with existing health knowledge tended to be accepted while
      pseudoscientific knowledge was regarded skeptically and concerns were raised over
      the accuracy and believability of the pseudoscientific claims. It appears that
      scientific awareness may play a part in consumers' ability to critically examine
      scientifically and pseudoscientifically based advertising claims.

PMID- 19391379
TI  - Parental views on pediatric vaccination: the impact of competing advocacy
      coalitions.
AB  - The debate on pediatric vaccination policy has been characterized by the presence
      of two distinct coalitions: those in favor of current vaccination policies and
      those expressing concern about these policies. The target of these coalitions is
      the vaccination decision of parents. To determine their influence, we conducted
      four focus groups in Toronto, Canada examining parental decision-making
      concerning pediatric vaccination. Our focus groups consisted of both fathers and
      mothers and parents who fully vaccinated and those who did not. Using the
      Advocacy Coalition Framework as an analytic guide, we identified several themes
      that provided insights into how effective the two coalitions have been in
      conveying their viewpoints. In general, we identified a variety of levels of
      belief systems existing amongst parents concerned about vaccination, some more
      amenable to change than others. We found that the choice to not vaccinate was
      largely a result of concerns about safety and, to a lesser extent, about lack of
      effectiveness. These parental views reflected the ability of the coalition
      concerned about vaccination to challenge parents' trust in traditional public
      health sources of information. In contrast, the parental decision to vaccinate
      was due to recognizing the importance of preventing disease and also a
      consequence of not questioning recommendations from public health and physicians
      and feeling pressured to because of school policies. Importantly, parents who
      fully vaccinate appear to have weaker belief systems that are potentially
      susceptible to change. While current policies appear to be effective in
      encouraging vaccination, if trust in public health falters, many who currently
      support vaccination may reevaluate their position. More research needs to be
      conducted to identify approaches to communicate the risks and benefits of
      vaccination to parents.

PMID- 19391380
TI  - The use of selected community groups to elicit and understand the values
      underlying attitudes towards biotechnology.
AB  - Focus groups were used to examine the social, cultural and spiritual dimensions
      of biotechnology through an analysis of five selected community groups (total n =
      68): scientists, Buddhists, business people, mothers with young children and the
      environmentally active. Participants from all groups were united in their
      perspective on three of the value spheres explored: health and welfare of
      family/society; maintaining/preserving the environment; and ethical
      considerations (e.g. welfare of animals, sanctity of life). However, values
      regarding science and business differentiated scientists and business people from
      the remaining community segments. Business people were more likely to adhere to
      "productionism," resulting in a greater acceptance of biotechnology, since
      business people did not hold the same resentment toward the business sphere held
      by other community segments. Scientists were far more accepting of the norms and
      values inherent in the sphere of science, believing science to be more
      predictable and controllable than general public perceptions. The disparity in
      worldviews for this value sphere meant scientists and laypeople did not
      communicate at the same level, in spite of having the same concerns for health
      and the environment. This resulted in feelings of frustration and powerlessness
      on the part of the layperson and the scientist.

PMID- 19391381
TI  - Teaching about ozone layer depletion in Turkey: pedagogical content knowledge of
      science teachers.
AB  - The purpose of this study was to investigate the pedagogical content knowledge of
      Prospective Science Teachers (PSTs) on the topic of "ozone layer depletion." In
      order to explore PSTs' subject matter knowledge on ozone layer depletion, they
      were given a form of multiple-choice test where they needed to write the reasons
      behind their answers. This test was completed by 140 PSTs in their final year at
      the College of Education. Individual interviews were carried out with 42 randomly
      selected PSTs to determine their pedagogical knowledge about ozone layer
      depletion. Data were obtained from the study which indicate that the PSTs did not
      have adequate subject matter and pedagogical knowledge to teach the topic of
      ozone layer depletion to middle school students. It was also evident that the
      PSTs held various misconceptions related to ozone layer depletion. PSTs'
      inadequate pedagogical knowledge was found in the areas of the curriculum,
      learning difficulties of students, and instructional strategies and activities.
      This study provides some pedagogical implications for the training of science
      teachers.

PMID- 19391382
TI  - [Comunities of knowledge. Schools and colleges in Paris in the XIIIth century].
AB  - The social and institutional history of the university of Paris still frequently
      remains detached from the study of the intellectual dynamics which were produced
      in its midst. The concept of "communities of knowledge" allows us to fill this
      gap by narrowly associating the history of knowledge to its concrete conditions
      of production and teaching. This model permits us to give attention to the
      maintenance, in the midst of the Parisian university of diverse "schools" endowed
      with orientations and specific programmes of research. The appearance of colleges
      can equally be situated in this perspective, which permits us to better grasp the
      interaction between the political and intellectual stakes which lay stress on the
      history of the university in the XIIIth century. Finally, it neveals the image of
      an institution more fragmented than unified.

PMID- 19391383
TI  - [Aspects of fatigue in medieval anthropology].
AB  - Psychosomatic sympton of the sinful human soul, progress of natural and
      progressive wear of the psychic or corporeal machinery, exclusive property of the
      world of bodies or place of the obligatory link between the intellect and the
      body, fatigue crosses the philosophical and theological medieval literature. The
      various treatments of fatigue can, in their turn, serve as symptoms to
      differentiate the medieval anthropologies. This article presents four of their
      figures: the anthropology of danger elaborated by Augustin, Greek and Arabe
      medical diagnosis which is passed on the XIth century, and the readings of
      Aristotle's psychology by Albert the Great and Thomas Aquinas in the XIIIth
      century.

PMID- 19391384
TI  - [Poetry, science and politics. A generation of Italian intellectuals (1290
      1330)].
AB  - Nothing is more false than the image of Dante as an isolated genius standing out
      against his epoch. On the contrary he belongs to a very characteristic generation
      of italian intellectuals: laymen, often active in more than one domain,
      practicing abundantly poetic expression, engaged in political action, these
      scholar-citizens share equally a strong historical conscience. Their inventivity
      is manifested in philosophy, in medecine and in law, as well as in literary
      expression. Aside from these endogenous factors, a key to this phenomenon is
      linked to the active reception of the naturalistic knowledge elaborated in Paris,
      which is read in Italy outside of the control of theologians. The parallel
      journeys of a dozen uncommon personalities show the necessity of enlarging the
      habitual frames of medieval intellectual history.

PMID- 19391385
TI  - [Loss of strength in the arms for 20 years. The patient cannot whistle and drink
      with a drinking straw].

PMID- 19391386
TI  - [Above all meniscus damage: what is the value of MRI? (interview by Dr. Thomas
      Meissner)].

PMID- 19391387
TI  - [There are no meridians and acupuncture works anyway].

PMID- 19391388
TI  - [General practice home pages: valued by many physicians, but often vulnerable].

PMID- 19391389
TI  - [Kidney diagnosis in general practice].

PMID- 19391390
TI  - [Recurrent cramping abdominal pain. What is going on in the large intestine?].

PMID- 19391391
TI  - [Nicotine throttles blood supply and damages the immune system. Passive smokers
      in the uterus].

PMID- 19391392
TI  - [General practice problem somatoform disorders. Helping the tiresome patients].

PMID- 19391393
TI  - [Alternative methods are popular. Conflicts with faith-based medicine].

PMID- 19391394
TI  - [Integrative medicine?].

PMID- 19391395
TI  - [Alternative diagnostic methods].

PMID- 19391396
TI  - [Static magnets for reducing pain].

PMID- 19391397
TI  - [Morbiliform exanthema of the trunk in childhood. Harmless exanthema or dangerous
      complication?].

PMID- 19391398
TI  - [Interactions in the family doctor's office: when pharmacotherapy itself becomes
      a problem].

PMID- 19391399
TI  - [Straight tips for stoma care].

PMID- 19391400
TI  - [Occupational accident--strong in electrocution].

PMID- 19391401
TI  - [How can winter sports be made safer? (interview by Maria Weiss)].

PMID- 19391402
TI  - [Near death experiences do not have a purely physiologic explanation].

PMID- 19391403
TI  - [Continuing to support the family practitioner as the pilot].

PMID- 19391404
TI  - [Without treatment the crash threatens].

PMID- 19391405
TI  - [Follow-up of ADHD patients. Adults "fidget" differently].

PMID- 19391406
TI  - [Acute respiratory insufficiency emergency].

PMID- 19391407
TI  - [Gastrointestinal tumours. Advances through differential therapeutic strategy].

PMID- 19391408
TI  - [Actual achievements in the therapy of esophagogastric carcinomas].

PMID- 19391409
TI  - [The up-to-date achievements in the prevention, treatment and after care of
      colorectal cancer].

PMID- 19391410
TI  - [Actual achievements in the therapy of hepatic metastases in patients with
      colorectal cancer].

PMID- 19391411
TI  - ["Minor foot curses": Kohler's disease II].

PMID- 19391412
TI  - [Emergency checklist: clavicle fracture].

PMID- 19391413
TI  - [Practical aspects of diabetes care in the elderly].

PMID- 19391414
TI  - [Chronic rhinosinusitis and aspirin intolerance].

PMID- 19391415
TI  - [Therapy of gastric acid-induced illnesses in general practice. The first
      pantoprazole generic drug has arrived].

PMID- 19391416
TI  - [Taking metabolic pathways into consideration. Approved drug against problematic
      interactions ].

PMID- 19391417
TI  - Bipartisan politics and practical knowledge: advertising of public science in two
      London newspapers, 1695-1720.
AB  - This article explores the enticement of consumers for natural philosophy (buyers
      of books, audiences at public lectures and purchasers of instruments) in London
      between 1695 and 1720 through advertisements placed in two political newspapers.
      This twenty-five-year period witnessed both the birth of public science and the
      rage of party politics. A consideration of public science adverts within the Whig
      leaning Post Man and the Tory-leaning Post Boy reveals that members of both the
      Whig and Tory parties were equally targeted and that natural philosophy was sold
      to London's reading population in bipartisan fashion. In the process of
      integrating natural philosophy into the wider culture through commercial sales,
      political allegiances were not imprinted on the advertising process. This
      conclusion raises questions regarding the historiographical assertion of Whig
      supported public science and Tory opposition to it at the level of consumers.

PMID- 19391418
TI  - Presbyterians and science in the north of Ireland before 1874.
AB  - In his presidential address to the Belfast meeting of the British Association for
      the Advancement of Science in 1874, John Tyndall launched what David Livingstone
      has called a 'frontal assault on teleology and Christian theism'. Using Tyndall's
      intervention as a starting point, this paper seeks to understand the attitudes of
      Presbyterians in the north of Ireland to science in the first three-quarters of
      the nineteenth century. The first section outlines some background, including the
      attitude of Presbyterians to science in the eighteenth century, the development
      of educational facilities in Ireland for the training of Presbyterian ministers,
      and the specific cultural and political circumstances in Ireland that influenced
      Presbyterian responses to science more generally. The next two sections examine
      two specific applications by Irish Presbyterians of the term 'science': first,
      the emergence of a distinctive Presbyterian theology of nature and the
      application of inductive scientific methodology to the study of theology, and
      second, the Presbyterian conviction that mind had ascendancy over matter which
      underpinned their commitment to the development of a science of the mind. The
      final two sections examine, in turn, the relationship between science and an
      eschatological reading of the signs of the times, and attitudes to Darwinian
      evolution in the fifteen years between the publication of The Origin of Species
      in 1859 and Tyndall's speech in 1874.

PMID- 19391419
TI  - Let consumers run health care.

PMID- 19391420
TI  - CMS and the Defense Department pilot projects could jump-start PHR use. Consumers
      say they want a digital record of their health, but so far few have one.

PMID- 19391421
TI  - Inspired staff can see tou through hard times. Interviewed by Bill Santamour.

PMID- 19391422
TI  - Seeing things through a child's eyes. ICU nurse eases anxiety and tension for
      children visiting their sick parents.

PMID- 19391424
TI  - Encouraging hospitalists to stick with you. Turnover rate cause for concern;
      workload big reason for leaving a job.

PMID- 19391423
TI  - Education, staffing reforms urged to equip nurses to use IT. Group proposes ways
      to give RNs more skills, more say on technology.

PMID- 19391425
TI  - People, get ready. This is our chance to truly transform health care.

PMID- 19391426
TI  - Plugging in a nation.
AB  - The government's $19 billion in IT funding could hasten a true EHR. Are you
      prepared to spend your share, and to help wire docs?

PMID- 19391427
TI  - Bringing doctors into the digital fold. Even with Stark relaxed, hospital
      physician IT links have been slow to develop. That could change.

PMID- 19391428
TI  - Practice makes perfect. Michigan medical school uses simulation center training
      to produce more competent, confident students.

PMID- 19391429
TI  - Not so hot. Hospital construction boom starts to cool, annual survey shows.

PMID- 19391430
TI  - Consumer research: Understanding how people shop for health care can be an
      effective strategic and financial planning tool.
AB  - Understanding how people shop for health care is an effective strategic and
      financial planning tool. Consumer loyalty takes more than curing their ailments.

PMID- 19391431
TI  - The hardest cuts of all.
AB  - The bleak economy has forced a number of hospitals to lay off staff and more are
      likely. But workforce decisions must balance current realities with long-term
      plans for growth.

PMID- 19391432
TI  - Hospitals in pursuit of excellence.

PMID- 19391433
TI  - 264 years is too long. We need to better educate and integrate research into
      practice.

PMID- 19391434
TI  - [Home medication cabinets and self-medication: a source of potential health
      threats].

PMID- 19391435
TI  - [Active pharmacovigilance in practice].

PMID- 19391436
TI  - [Orphan drugs].

PMID- 19391437
TI  - Dextromethorphan hydrobromide preparations on the Belgian market--a comparative
      study.
AB  - Liquid preparations for oral use containing dextromethorphan hydrobromide were
      verified on identity, content and microbiological quality. The assay method was
      previously validated according to international guidelines. All examined products
      complied with the postulated requirements.

PMID- 19391438
TI  - [Hemorrhagic complications of anti-vitamin K].
AB  - Adverse events related to oral anticoagulants represent a major public health
      problem. Hemorrhagic episodes are the most frequent complications and can be life
      threatening. A 10 month prospective survey on all cases treated with anti-vitamin
      K (AVK), and admitted to emergency room of CHU Grenoble, was conducted to
      identify the hemorrhagic adverse drug events (HADE). The evaluation support was a
      directive questionnaire and consisted of 3 parts: patient characteristics,
      patient's medicated treatment and the hemorrhagic event. 216 patients treated
      with AVK were identified and 68 of them presented a hemorrhagic adverse drug
      event. 60 patients older than 65 years out of 158, presented HADE (38%); versus 8
      patients < or = 65 years out of 58 (RR = 2.75; p = 0.0007). Among the patients
      who have their INR > or = 5, 79% developed HADE versus 16% in the group who had
      their INR < 5 (< 0.0001). In the group of patients who had a change in drug
      therapy within the 7 days preceding their admission, 47% developed HADE versus
      25% of patients whose treatment was not modified: Anti-microbial agents were the
      drug most frequently involved. The patient's knowledge of INR value and signs of
      excess AVK were significant. Concerning missed dose, 48 patients declared taking
      the missed dose with the next dose or when they remembered: 35% of them developed
      HADE (p = 0.49).

PMID- 19391439
TI  - The 2011 census taking shape: the selection of topics and questions.
AB  - The UK Statistics Authority's proposals for the next census in England and Wales,
      to be taken in March 2011, were published and presented to Parliament and the
      National Assembly for Wales in a Government White Paper on 11 December 2008.
      These have been published at this time--some two years or more before the census
      itself--in order for Parliament and the public alike to be given the opportunity
      for informed discussion on the design of the next census, and particularly the
      proposed questions to be included, before the secondary legislation necessary for
      the census to take place is considered by Parliament towards the end of
      2009Iearly 2010. This article--the first of two to report on the significant
      recent developments in the design of the census--comments on the questions that
      are being proposed in England and Wales and notes the degree in which these are
      being harmonised across the rest of the UK and how comparable they are with those
      asked in 2001. The main uses to which the information collected will be put are
      described. A second article, scheduled for the summer issue of Population Trends,
      will focus on the key methodological and operational developments designed to
      improve coverage in the 2011 Census and the quality of the resulting statistical
      outputs.

PMID- 19391440
TI  - UK resident population by country of birth.
AB  - In August 2008, estimates of the 'Population by country of birth and nationality'
      were published for the first time by the Office for National Statistics (ONS)
      from the Annual Population Survey (APS). Tables were published for the calendar
      year 2004 to 2007. This article provides an analysis of the published figures,
      and some background information about the APS.

PMID- 19391441
TI  - What does the 2001 census tell us about the new parliamentary constituencies?
AB  - New parliamentary constituency boundaries will come into effect in England, Wales
      and Northern Ireland by the time of the next general election, with the majority
      of boundaries used in the 2005 General Election set to change. The constituency
      boundaries used in Scotland in 2005 will remain unchanged at the next general
      election. The article discusses the recent boundary changes, and attempts some
      analyses based upon population, ethnicity, religion, health and other variables.

PMID- 19391442
TI  - Diet, tuberculosis, and the paleopathological record.
AB  - Osseous manifestation of infectious disease is of paramount importance to
      paleopathologists seeking to interpret ancient health, but the relationships
      among infectious agent exposure, development of disease, and skeletal involvement
      are complex. The outcome of an exposure strongly depends on multiple factors,
      including ecology, diet, nutrition, immune function, and the genetics of pathogen
      and host. Mycobacterial diseases are often studied in ancient remains but also
      are especially influenced by these factors; individual and population differences
      in severity and course are apparent following onset of active disease. The
      osteological record for these diseases represents the complex interplay of host
      and pathogen characteristics influencing within- and among-individual skeletal
      lesion prevalence and distribution. However, many of these characteristics may be
      assessed independently through the archaeological record. Here, we explore the
      contributions of dietary protein and iron to immune function, particularly the
      course and outcome of infection with Mycobacterium tuberculosis. We emphasize how
      nutrition may influence the dissemination of bacilli to the skeleton and
      subsequent formation of diagnostic lesions. We then generate models and
      hypotheses informed by this interplay and apply them to four prehistoric New
      World areas. Finally, discrepancies between our expectations and the observed
      record are explored as a basis for new hypotheses.

PMID- 19391443
TI  - Size and place in the construction of indigeneity in the Russian Federation.
AB  - Within the Russian Federation there are nearly 200 recognized "nationalities,"
      approximately 130 of which could claim to be "indigenous." However, only 45
      peoples are officially recognized as "indigenous small-numbered peoples of the
      Russian Federation" and thereby qualify for the rights, privileges, and state
      support earmarked for indigenous peoples. This status is conditioned upon a
      maximum group size of 50,000. While experts insist that this numerical criterion
      is provisional and without serious political implications, our fieldwork
      demonstrates that it has become a social fact that cannot be ignored, especially
      in light of the 2002 All-Russia Census and the release of its results in 2004.
      This numerical benchmark forces a dichotomization into small-numbered versus non
      small-numbered peoples and creates a peculiar type of identity politics based on
      ethnic-group size. The "indigenous small-numbered" status is also conditioned
      upon a set of overlapping but often contradictory residency requirements. Using
      case studies from southern Siberia and the north of European Russia, we document
      the dynamic interplay between these dimensions of identity and the opportunities
      for maneuvering in the competition for the benefits that attach to certain
      categories. However, indigenous peoples who engage in such identity politics run
      the risk of becoming "incarcerated" within the confines of those categories.

PMID- 19391444
TI  - Community, identity, and conflict: Iron Age warfare in the Iberian Northwest.
AB  - This paper proposes a new view of conflict in European Iron Age societies:
      considering isolationism as an alternative to warfare. Study of the castros
      (fortified settlements) of the Iberian Northwest suggests the organization of
      production as a main explanatory element in the emergence of identities based on
      exclusion and the imposition of communal structures of power. The relationship
      between these communities must have been one of conflict, and the unequal
      productive success of domestic units and the requirement of external marriage
      interchanges created realms of interaction in which internal conflict surely
      arose. These tendencies were kept in check by controlling settlement growth.
      Although a conflict-prone situation is documented in the archaeological record,
      there is no evidence that warfare as an endemic reality created groups of
      warriors. Warfare-related activity in these Iron Age societies was neither heroic
      nor hierarchical. Warfare did not determine the form of society but rather was
      related to the productive and reproductive organization of the societies that
      engaged in it.

PMID- 19391445
TI  - Primate vocalization, gesture, and the evolution of human language.
AB  - The performance of language is multimodal, not confined to speech. Review of
      monkey and ape communication demonstrates greater flexibility in the use of hands
      and body than for vocalization. Nonetheless, the gestural repertoire of any group
      of nonhuman primates is small compared with the vocabulary of any human language
      and thus, presumably, of the transitional form called protolanguage. We argue
      that it was the coupling of gestural communication with enhanced capacities for
      imitation that made possible the emergence of protosign to provide essential
      scaffolding for protospeech in the evolution of protolanguage. Similarly, we
      argue against a direct evolutionary path from nonhuman primate vocalization to
      human speech. The analysis refines aspects of the mirror system hypothesis on the
      role of the primate brain's mirror system for manual action in evolution of the
      human language-ready brain.

PMID- 19391446
TI  - Elder abuse--a wake up call.

PMID- 19391447
TI  - Incidental occult carcinomas in total thyroidectomy for benign diseases of the
      thyroid.
AB  - BACKGROUND: Total thyroidectomy is increasingly recognised as the preferred
      surgical option for benign diseases of the thyroid. One factor contributing
      towards this change in policy is reports of incidental carcinomas in the resected
      specimens. METHODS: This was a prospective study of patients, who underwent total
      thyroidectomy for benign diseases of the thyroid at the University Surgical Unit,
      Colombo North Teaching Hospital from January 2003 to December 2005. RESULTS:
      There were 68 patients (67 females) aged 28 to 67 years (mean 44.2 (SD=11.1). In
      6 (8.8%) patients, histological examination of the post-operative specimen showed
      incidental carcinomas: 2 papillary, 2 medullary and 2 follicular carcinomas.
      There was no significant difference in age, clinical presentation and functional
      thyroid status of patients with incidental carcinomas and those with
      histologically confirmed benign diseases. CONCLUSIONS: Occurrence of incidental
      thyroid cancers was 8.8% in this series, and they were difficult to predict pre
      operatively. The policy of performing total thyroidectomy for benign disease of
      the thyroid obviates the need for further surgery if an incidental carcinoma is
      found.

PMID- 19391448
TI  - Trans rectal ultra sound guided prostate biopsies: a single centre experience in
      Sri Lanka.
AB  - BACKGROUND: Trans rectal ultrasound guided prostate biopsy (TRUS) was introduced
      to Sri Lanka in 2002. OBJECTIVES: 1. To study clinicopathological features of
      males subjected to TRUS biopsy 2. To compare estimation of tumour burden by two
      methods in carcinoma prostate (CaP). METHODS: 749 symptomatic males subjected to
      TRUS biopsy over 64 months at a single centre. Information was retrieved from
      case records. Tumour burden in CaP was calculated as: 1. Calculated tumour burden
      (CTB)--total percentage tumour in each core/total number of cores 2. Percentage
      positive biopsy cores (PPBC)--number of positive cores/total number of cores X
      100. SPSS 15.0, student's t test and Spearman's rank correlation coefficients
      were used for statistical analysis. RESULTS: 35.2% had CaP, microacinar in type.
      34.88% were poorly differentiated. CaP was frequent among older patients
      (P<0.00001). The prostate volume in CaP was significantly lower than in the
      benign group (P<0.05). Prostate specific antigen (PSA) level was significantly
      higher in CaP (P<0.00001). A 99.6% sensitivity and 4.7% specificity was observed
      at PSA of 4 ng/ml for detecting CaP. Specificity was 98% at 25.5 ng/ml, with a
      sensitivity of 44.4%. CTB and PPBC had similar correlations with
      biochemical/histological parameters of CaP and were strongly correlated (0.786).
      INTERPRETATION: Males with CaP were older, had higher PSA levels and smaller
      prostates. A cut off level of PSA >4 ng/ml could be used for directing
      symptomatic patients for TRUS biopsy to detect CaP, keeping in mind that
      specificity is 98% only at 25.5 ng/ml. Both CTB and PPBC could be used to
      calculate tumour burden in TRUS with CaP.

PMID- 19391449
TI  - Prevalence and correlates of physical and emotional abuse among late adolescents.
AB  - OBJECTIVES: To estimate the prevalence of physical and emotional abuse reported
      by late adolescent school children in southern Sri Lanka, and to identify
      demographic and behavioural correlates of such abuse. METHOD: A cross-sectional
      survey was administered to a sample of 1099 male and 1290 female late
      adolescents, through schools in the southern province. Self-report anonymous
      questionnaires were used. Study variables included age, gender, body mass index
      (BMI), socioeconomic status, deliberate self harm, substance use, school
      absenteeism and family conflicts. RESULTS: Of the total, 22.4% (n = 246) of males
      and 15.7% (n = 202) of females reported having been subjected to physical abuse
      at least a few times in the 3 months preceding the survey (p<0.05), and 31.3% (n
      = 324) of males and 25.4% (n = 328) of females reported having been subjected to
      emotional abuse at least a few times in the 3 months preceding the survey
      (p<0.05). Logistic regression analyses revealed that school absenteeism,
      deliberate self-harm, substance use, and family conflict were associated with
      physical and emotional abuse. Socio-economic status and BMI were not found to be
      associated with physical and emotional abuse. CONCLUSION: Physical and emotional
      abuse are important health issues among late adolescent school children in Sri
      Lanka. Further research is needed to better understand the causal direction of
      the associations between physical and emotional abuse experiences, and health
      related behaviours.

PMID- 19391450
TI  - Paracetamol poisoning below toxic level causing liver damage in a fasting adult.

PMID- 19391451
TI  - A case of peritoneal encapsulation syndrome.

PMID- 19391452
TI  - A case of distal renal tubular acidosis, Southeast Asian ovalocytosis and
      possible fluorosis.
AB  - A 39-year old man had periodic paralysis due to hypokalaemia. Investigations led
      to the diagnosis of distal renal tubular acidosis (dRTA) and Southeast Asian
      ovalocytosis (SAO). Both can originate in mutations of the anion-exchanger 1 gene
      (AE1), which codes for band 3, the bicarbonate/chloride exchanger in both the red
      cell membrane and the basolateral membrane of the collecting tubule alpha
      intercalated cell. The finding of diffuse osteosclerosis led to the suspicion of
      coexisting fluorosis.

PMID- 19391454
TI  - Prevalence of chronic kidney disease in two tertiary care hospitals: high
      proportion of cases with uncertain aetiology.

PMID- 19391453
TI  - Spontaneous bilateral tubal ectopic pregnancy.
AB  - A 28-year-old woman presented at eight weeks and four days of gestation,
      according to her menstrual dates, complaining of painless vaginal bleeding for
      three days. Her urinary pregnancy test was positive. Initial transvaginal
      ultrasound demonstrated an irregular complex structure with a fluid filled centre
      in the right adnexum. Despite the diagnosis of a possible underlying unruptured
      right tubal ectopic pregnancy, she declined surgical intervention and was managed
      expectantly as an inpatient. When she complained of increasing abdominal pain
      with haemodynamic instability, an emergency laparotomy was performed and a
      diagnosis of bilateral tubal ectopic pregnancy was made.

PMID- 19391455
TI  - A tanned cadaver.

PMID- 19391456
TI  - Age of onset of menarche and secondary sexual characters in Sri Lankan girls of
      two different regions.

PMID- 19391457
TI  - Possible familial gestational spontaneous ovarian hyperstimulation syndrome due
      to mutation of FSH receptors (FGSOHS).

PMID- 19391458
TI  - Screening newborns for congenital hypothyroidism.

PMID- 19391459
TI  - Suicidal risk assessment and depression.

PMID- 19391460
TI  - Modified simple percutaneous suprapubic cystostomy.

PMID- 19391461
TI  - Nutrient sensing in the gastrointestinal tract: possible role for nutrient
      transporters.
AB  - Although it is well established that the presence of nutrients in the gut lumen
      can bring about changes in GI function, the mechanisms and pathways by which
      these changes occur has not been fully elucidated. It has been known for many
      years that luminal nutrients stimulate the release of hormones and regulatory
      peptides from gut endocrine cells and that luminal nutrients activate intrinsic
      and extrinsic neural pathways innervating the gut. Activation of gut endocrine
      cells and neural pathways by nutrients in the gut lumen is key in coordination of
      postprandial GI function and also in the regulation of food intake. Recent
      evidence suggests that these pathways can be modified by long term changes in
      diet or by inflammatory processes in the gut wall. Thus it is important to
      determine the cellular and molecular mechanisms underlying these processes not
      only to increase our understanding of as part of basic physiology but also to
      understand changes in these pathways that occur in the presence of
      pathophysiology and disease. This review summarizes some of the latest data that
      we have obtained, together with information from the other laboratories, which
      have elucidated some of the mechanisms involved in nutrient detection in the gut
      wall. The focus is on monosaccharides and protein hydrolysates as there is some
      evidence for a role for nutrient transporters in detection of these nutrients.

PMID- 19391464
TI  - De Fabrica et Action.

PMID- 19391463
TI  - Lipid raft organization and function in the small intestinal brush border.
AB  - The enterocyte brush border of the small intestine is a highly specialized
      membrane designed to function both as a high capacity digestive/absorptive
      surface of dietary nutrients and a permeability barrier towards lumenal
      pathogens. It is characterized by an unusually high content of glycolipids
      (approximately 30% of the total microvillar membrane lipid), enabling the
      formation of liquid ordered microdomains, better known as lipid rafts. The
      glycolipid rafts are stabilized by galectin-4, a 36 kDa divalent lectin that
      cross-links galactosyl (and other carbohydrate) residues present on membrane
      lipids and several brush border proteins, including some of the major hydrolases.
      These supramolecular complexes are further stabilized by intelectin, a 35 kDa
      trimeric lectin that also functions as an intestinal lactoferrin receptor. As a
      result, brush border hydrolases, otherwise sensitive to pancreatic proteinases,
      are protected from untimely release into the gut lumen. Finally, anti-glycosyl
      antibodies, synthesized by plasma cells locally in the gut, are deposited on the
      brush border glycolipid rafts, protecting the epithelium from lumenal pathogens
      that exploit lipid rafts as portals for entry to the organism.

PMID- 19391462
TI  - Vitamin C transporters.
AB  - Vitamin C is a wide spectrum antioxidant essential for humans, which are unable
      to synthesize the vitamin and must obtain it from dietary sources. There are two
      biologically important forms of vitamin C, the reduced form, ascorbic acid, and
      the oxidized form, dehydroascorbic acid. Vitamin C exerts most of its biological
      functions intracellularly and is acquired by cells with the participation of
      specific membrane transporters. This is a central issue because even in those
      species capable of synthesizing vitamin C, synthesis is restricted to the liver
      (and pancreas) from which is distributed to the organism. Most cells express two
      different transporter systems for vitamin C; a transporter system with absolute
      specificity for ascorbic acid and a second system that shows absolute specificity
      for dehydroascorbic acid. The dehydroascorbic acid transporters are members of
      the GLUT family of facilitative glucose transporters, of which at least three
      isoforms, GLUT1, GLUT3 and GLUT4, are dehydroascorbic acid transporters. Ascorbic
      acid is transported by the SVCT family of sodium-coupled transporters, with two
      isoforms molecularly cloned, the transporters SVCT1 y SVCT2, that show different
      functional properties and differential cell and tissue expression. In humans, the
      maintenance of a low daily requirement of vitamin C is attained through an
      efficient system for the recycling of the vitamin involving the two families of
      vitamin C transporters.

PMID- 19391465
TI  - Labor of love: foster mothers, caregiving, and welfare reform.
AB  - Using a telephone survey, this study examined the experiences of 100 foster
      mothers who receive aid through Temporary Assistance for Needy Families (TANF).
      Foster mothers reported numerous difficulties with TANF, including frequent
      sanctions and case closings, limited work and training opportunities, and
      pervasive material hardships. Foster children exhibited high levels of emotional
      and behavior problems. The data suggest that lack of access to child care and
      pressure to become self-sufficient may contribute to a decreased pool of foster
      mothers.

PMID- 19391466
TI  - Does family group decision making affect child welfare outcomes? Findings from a
      randomized control study.
AB  - This article describes the evaluation of two family group decision-making
      programs (FGDM; Fresno n = 60; Riverside n = 50) administered under the
      California Title IV-E Waiver Demonstration Project. This is the only evaluation
      using random assignment to examine FGDM. Overall, results did not indicate more
      positive outcomes for children receiving the intervention, but did indicate that
      children were not worse than those receiving traditional services; outcomes
      examined were related to child safety, placement stability, and permanence.

PMID- 19391467
TI  - The nature of parental supervisory neglect.
AB  - The primary purpose of this study is to determine whether different types of
      supervision problems such as leaving a child alone and leaving a child with an
      inadequate caregiver have different correlates and consequences for children. A
      case-comparison design was used to compare four types of supervision problems.
      Data were extracted from child protective services investigative reports. The
      results showed that each type of supervision problem had a distinct set of
      characteristics. Recommendations for assessing and treating different types of
      supervision problems are addressed.

PMID- 19391468
TI  - Children in foster care: before, during, and after psychiatric hospitalization.
AB  - Although it is generally accepted that foster children are at greater risk for
      mental health problems than are children in the general population, very little
      is known about the smaller group of foster children admitted to psychiatric
      hospitals. The present study sought to determine whether foster children admitted
      to inpatient care are a distinct and more vulnerable group than other
      hospitalized children and found that they are. Youth admitted from the foster
      care system were found to have higher rates of externalizing problems and
      diagnoses, and lower social competence relative to other inpatient children. They
      were also found to have a distinguishing pattern of service use including first
      admissions at younger ages, higher numbers of restraints in hospital, and greater
      likelihood of readmission. These findings point to pressing needs for additional
      research to improve understanding of the vulnerabilities and inpatient care needs
      of foster children and for better initiatives to prevent early and recurrent
      hospitalization.

PMID- 19391469
TI  - The social service divide: service availability and accessibility in rural versus
      urban counties and impact on child welfare outcomes.
AB  - An empirical study of 75 counties in a state found that social services are more
      available and accessible in urban versus rural counties, signaling a need for
      public policy addressing service allocation. The study also found a relationship
      between the accessibility of intensive family preservation services and reentry
      into foster care, a child welfare outcome. Implications for achieving outcomes
      affecting safety, permanence, and well-being of children are discussed.

PMID- 19391470
TI  - Should I stay or should I go? A comparison study of intention to leave among
      public child welfare systems with high and low turnover rates.
AB  - This comparison study analyzes the commonalties, similarities, and differences on
      supervisory and organizational factors between a group of high turnover systems
      and a group of low turnover systems. Significant differences on organizational
      factors, but not on supervisory factors, emerged from the statistical analysis.
      Additionally, this study found that low turnover is not necessarily predictive of
      a healthy organizational environment. Implications for turnover reduction and
      prevention are provided in conclusion.

PMID- 19391471
TI  - Meeting the long-term needs of families who adopt children out of foster care: a
      three-year follow-up study.
AB  - The purpose of this study was to assess the extent to which agency and nonagency
      supportive resources contributed to the stability and well-being of 34 newly
      adoptive families over 3 years. Results revealed significant pre- to post
      adoption declines in families' contact and satisfaction with formal and informal
      helping resources. Greater pre-adoption contact with formal adoption agency staff
      predicted adoption stability and lower levels of family conflict at the 3-year
      assessment. The results highlight the importance of providing adoptive families
      with formal and informal support that meets their evolving needs.

PMID- 19391472
TI  - [Conference "Ontogeny and Evolution" (Moscow, 14-15 May 2008)].

PMID- 19391473
TI  - [Evolution of adaptive immunity].
AB  - The current state of the problem of emergence and evolution of adaptive immunity
      in different taxonomic groups of animals is analyzed. Special attention is given
      to the emergence and phylogenetic development of the lymphocyte, the key
      component of immune response, as well as to the evolutionary development of T-
      and B-cell immune systems, adaptive immune responses and their molecular
      regulators (cytokines), and antigen-recognition structures.

PMID- 19391474
TI  - [The role of heterochrony in the establishment of archetype in higher Echinoderm
      taxa].
AB  - The analysis based on paleontological data shows that the body plans of higher
      echinoderm taxa were established through the combination of previously developed
      characters. These combinations appeared due to various heterochronies and
      resulted in more or less complete filling of the morphological space of logical
      capabilities. The maximum rank of new taxa decreased with time. New body plans of
      higher taxa did not replace the old plans but rather overlay them, extending the
      hierarchy of body plans and the respective hierarchy of taxa. The macroevolution
      of echinoderms and other metazoans progressed from the formation of an archetype
      (a general body plan) to individual details, the development of structural plans
      of lower levels. Heterochrony resulted in mosaic evolution and obscurity of
      intermediate forms.

PMID- 19391475
TI  - [Evolution of brain development in amphibians].
AB  - Principal events in the early embryonic development of the nervous system, from
      neurulation to primary differentiation, are considered in different amphibian
      species. Attention is paid to numerous interspecific differences in the structure
      of neuroepithelium and the patterns of neurulation and embryonic brain
      segmentation. The data presented indicate that similarity in brain developmental
      patterns is apparently explained by universality of morphogenetic mechanisms
      rather than by the common origin of particular species. A hypothesis is proposed
      that similarity in the shape of the developing amphibian brain is determined by
      mechanisms of coding positional information necessary for histogenetic
      differentiation.

PMID- 19391476
TI  - [Morphogenetic approach to the formation of paired limbs in the course of
      tetrapodization].
AB  - Transition from sarcopterygians to tetrapods is analyzed based on new
      paleontological, ontogenetic, and molecular data. It is shown that transformation
      of skeletal fin elements into the tetrapod limb followed the patterns of
      divergent, parallel, and mosaic development. Morphogenetic plasticity and
      autonomy of these processes as well as the same developmental bauplan for the
      limbs of Urodela and Anura are proposed. Variations observed in these processes
      are regarded as a result of larval adaptations and heterochronies. The latter
      excludes recapitulation of successive archetypical states (transformation
      development of the fish fin into tetrapod limb). The idea that the digits are a
      novelty relative to the distal radials of the fin is supported.

PMID- 19391477
TI  - [Development of limbs in urodeles and the origin of tetrapod limbs].
AB  - On the basis of studies on serial sections of larval Ranodon sibiricus limbs and
      published data, the hypothesis of the origin of tetrapod limbs from the biserial
      archipterygium is proposed. The mesomeres of the central axis of the biserial fin
      correspond (in proximodistal direction) to the humerus, ulna, ulnare, all
      carpalia distalia, metacarpale 1, and phalanges of the first digit in the
      forelimb of caudate amphibians and to the femur, fibula, fibulare, tarsalia
      distalia, metatarsale 1, and phalanges of the first digit in the hind limb. The
      preaxial elements of the zygopodium and autopodium, which are positioned proximal
      to the digital arch, correspond to the preaxial rays of the biserial fin, and
      digits 2-5 correspond to its postaxial rays. As the fin transformed into the
      limb, the central axis curved preaxially, forming the digital arch and resulting
      in partial reduction and fusion of preaxial rays.

PMID- 19391478
TI  - [Molecular structure of allelic variants of microsatellite loci Du281 and Du47 in
      unisexual and bisexual lizard species of the genus Darevskia].
AB  - Experimental data on the molecular structure and variability of microsatellite
      loci in unisexual and bisexual lizard species of the genus Darevskia were
      analyzed. The allelic variants of Du281 and Du47 were found to differ in the
      number of monomers, the structure of microsatellite clusters, and point mutations
      in these clusters and flanking DNA. Interspecific comparison of alleles of these
      loci revealed both variable regions in the microsatellite clusters and allele
      specific evolutionarily conserved nucleotide groups. In general, the results of
      comparative structural analysis of allelic variants testify to a high genetic
      similarity of the unisexual and bisexual lizard species studied and reveals the
      characteristic features of their interspecies variability.

PMID- 19391479
TI  - [Evolution of the sex determination in mammals].
AB  - This review summarizes current concepts concerning the evolution of sex
      chromosomes and the cascade of sex-determining genes in mammals. Untypical sex
      determination systems in rodents lacking the Y-chromosome and Sry gene are
      considered using Ellobius as an example.

PMID- 19391480
TI  - [Skin derivatives in ontogeny and phylogeny of vertebrates].
AB  - The skin of vertebrates has numerous and diverse derivatives, either located
      within the epithelial sheet itself (glands) or extending above its surface
      (teeth, scales, feathers, hairs, etc.). Many of them have a modular structure and
      constitute structural-functional units. Ontogenetically, all skin derivatives are
      of ectomesodermal origin, and their morphogenesis is subject to metabolic
      control, heterochronies (divergence in the timing of origination and
      development), and regulation by means of tissue interactions and molecular
      signaling via similar pathways. The diversification (origination of morphological
      diversity) of skin derivatives within the same morphological type is explained by
      the development of new generations of ectomesodermal structures separated be
      heterochronies and regulated by changes in the gradients of molecular signaling
      pathways under the influence of environmental factors. Evolutionary relationships
      between the majority of skin derivatives are obscure, except for teeth and glands
      associated with sensory organs, which evolved together with the latter.
      Apparently, many vertebrate skin derivatives (scales, feathers, hairs, and
      glands) originated as innovations at nodal stages of phylogeny and subsequently
      evolved convergently or in parallel.

PMID- 19391481
TI  - [Butterflies (Lepidoptera, Diurna) in boreal forests of southeastern Russia: 1.
      Light coniferous forests].
AB  - Species groups formed in light coniferous forests prevailing in southeastern
      Russia are considered using the example of butterflies. Problems concerning the
      formation of species composition and its originality in some insects groups are
      discussed. A classification analysis of species checklists for twelve local
      faunas of Transbaikalia and the southern Russian Far East is performed. It is
      shown that the faunas of areas occupied by light coniferous forests have a common
      background.

PMID- 19391482
TI  - [Characteristics of tooth system in gekkonid lizards ( Teratoscincus, Gekkonidae)
      and other lizards (Gekkota, Sauria, Reptilia)].
AB  - The dentition and tooth crown microstructure of gekkonids and eublepharids are
      examined. Scanning electron microscopy shows that the lingual surface of teeth in
      these lizards has one, two, or, occasionally, several cusps separated by grooves.
      The teeth of geckoes usually have two (lingual and labial) cusps in the apical
      region. With respect to the number of teeth, the majority of Gekkota fall into
      two groups. The first includes a few species with many teeth (50 or more) in the
      dentary and maxilla, the eublepharids Goniurosaurus and Aeluroscalabotes, and the
      gekkonid Cyrtopodion louisiadensis. The second group, comprising most of the
      species, is subdivided into two subgroups, species with 20-30 or 30-40 teeth in
      jaw bones. Teratoscincus belongs to the first subgroup of the second group.

PMID- 19391483
TI  - [Exogenous and endogenous fluctuations of thermoregulatory activity in the
      honeybee].
AB  - Thermovision and thermometric methods were used to study temperature variations
      in honeybee nests and in aggregations of honeybees isolated from their families.
      Endogenous and exogenous circadian rhythms of thermoregulatory activity and their
      physiological mechanisms were revealed. The magnitude of changes in this activity
      in response to ambient temperature decreased from the beginning to the end of
      wintering, which was due to the existence of a genetically determined self
      regulation program in honeybees. The improvement of this program in the course of
      the species evolution contributed to transformation of a honeybee family into a
      reproducible biological unit.

PMID- 19391484
TI  - Aberrant tubulointerstitial immunoexpression of matrix metalloproteinases MMP-2,
      MMP-9 and tissue inhibitor of matrix proteinase-2 (TIMP-2) in acute cellular
      rejection of human renal allograft.
AB  - Acute cellular rejection (ACR) may initiate chronic allograft dysfunction with
      alterations in the extracellular matrix compartment (ECM). Turnover of ECM
      proteins is regulated by matrix metalloproteinases (MMPs). The aim of the present
      study was to determine the immunoexpression of MMP-2, MMP-9 and TIMP-2 in ACR,
      and to examine the relationship between expression of MMPs and
      monocytes/macrophages, transforming growth factor beta-1 (TGFbeta-1), and alpha
      smooth muscle actin (alpha-SMA). Immunoperoxidase study with antibodies against
      MMP-2, MMP-9, TIMP-2, CD68, TGFbeta-1 and alpha-SMA was carried out on 24 renal
      allograft biopsy specimens from patients with ACR and 11 allograft biopsy
      specimens from patients with no signs of rejection. Our study revealed increased
      immunoexpression of MMP-2, MMP-9 and TIM-2 in ACR as compared with controls, and
      significant positive correlations between immunostaining of MMP-2 and TGF-beta-1,
      as well as between MMP-2 and alpha-SMA. Increased immunoexpression of MMP-9 was
      positively correlated with alpha-SMA, and the number of interstitial CD68+cells.
      In conclusion our study supports a role of gelatinases in tissue damage in human
      renal acute cellular allograft rejection and provides some interesting insights
      into early renal remodeling which may lead to chronic allograft dysfunction.

PMID- 19391485
TI  - Estimation of diagnostic value of chosen markers of neural differentiation in
      neuroblastoma group of tumors and pPNETs.
AB  - Neuroblastoma and peripheral PNETs both are typical examples of wide group of
      small round blue cell tumors of childhood. Matured neuroblastoma show typical
      clinical presentation and easy to interpret microscopic picture. Unfortunately in
      everyday practice much commonly appeared less differentiated neuroblastomas with
      difficult to predict clinical behavior and impossible to diagnose in routine
      stain histologic view. Peripheral PNETs are found as morphologically similar
      entities to some neuroblastoma subtypes but they are treated as separate CD99
      positive group of tumors with different biology and clinical behavior. The aim of
      our study was to estimate the usefulness of neural markers expression
      (Neuroblastoma Marker, neurospecyfic enolase and neurofilaments) in routine
      separation between neuroblastoma tumors and pPNETs and between neuroblastoma
      subtypes according to currently used classification of those entities. We
      investigated 63 tumor tissue samples and found differences in expression of
      investigated markers between both neuroblastoma subgroups and neuroblastoma group
      of tumors and pPNETs.

PMID- 19391486
TI  - Ser326Cys polymorphism in DNA repair genes hOGG1 in breast cancer women.
AB  - Reduced DNA repair capacity can render a high risk of developing many types of
      cancer; including breast cancer. Polymorphisms in DNA repair genes may contribute
      the genetic instability and carcinogenesis. In the present work the distribution
      of genotypes and frequency of alleles of the Ser326Cys polymorphism of hOGG1 gene
      in breast cancer women were analysed. Blood samples were obtained from 100 women
      with breast cancer and control (n = 106). The polymorphism was determined by PCR
      RFLP methods. No association between Ser326Cys polymorphism of hOGG1 and breast
      cancer risk was observed. The distribution of the genotypes of the Ser326Cys
      polymorphism in both control and patients did not differ significantly (p > 0.05)
      from those predicted by the Hardy-Weinberg distribution. There were no
      significant differences (p > 0.05) in genotype distributions and allele
      frequencies between subgroups assigned to histological stage. The results suggest
      that the Ser326Cys polymorphism of hOGG1 gene may not be linked with appearance
      and development of breast cancer in polish women.

PMID- 19391487
TI  - Immunohistochemical expression of androgen receptor in salivary gland cancers.
AB  - Accidental discovery of androgen receptor (AR) expression in high-grade salivary
      gland cancer led to evaluation of that finding. In this study we evaluated the
      immunohistochemical expression of AR in a series of 37 formalin-fixed, paraffin
      embedded malignant salivary gland tumors using two commercially available
      antibodies. Nuclear immunoreactivity for AR was demonstrated in 3 of 4 salivary
      duct carcinomas, 2 of 7 adenocarcinomas NOS and 1 of 2 carcinoma ex pleomorphic
      adenoma for both antibodies. Expression of AR was evaluated semiquantatively
      according to Dako ER/PR pharmDx scoring guidelines. All positive cases came from
      male patients. There was no immunoreactivity seen in 13 adenoid cystic
      carcinomas, 7 mucoepidermoid carcinomas and 4 acinic cell carcinomas. The
      expression of AR in high-grade salivary gland cancers suggests a possible role
      for AR in the clinical management of these neoplasms.

PMID- 19391488
TI  - Perivascular epithelioid tumor (PEComa) of the falciform/ broad ligament.
AB  - PEComas localized in the region of falciform ligament and broad ligament are
      exceedingly rare. Most of them are built of spindle neoplastic cells. We report a
      case of epithelioid PEComa of the falciform ligament and/or broad ligament. There
      is only one report of such neoplasm in English-language literature.
      Histologically, the tumor was composed of nests of epithelioid clear cells
      stained positively for vimentin, HMB45, and SMA. Because of morphological
      features of the tumour (4 mitoses /20HPF, focal necrosis, and vascular invasion)
      we assess the neoplasm as potentially malignant.

PMID- 19391489
TI  - Lipofibromatosis presenting as a neck mass in eight-years old boy--a case report.
AB  - Lipofibromatosis is a very rare pediatric neoplasm with a histologically
      distinctive fibrofatty pattern. Some of the authors believe that this term should
      encompass several rare soft tissue tumors of childhood and that tumors of
      childhood which contain fat as an integral component warrant new classification.
      We present a case report of a neck tumor in eight-years old boy which shares
      clinical and morphological features similar to those originally described by
      Fetch et al. with peaceable with literature results of immunohistochemical
      stains.

PMID- 19391490
TI  - Comparison of running kinematics between elite and national-standard 1500-m
      runners.
AB  - The aim of this study was to determine whether elite 1500-m runners differ in
      their running kinematics from national-standard 1500-m runners. Six national
      standard male runners (seasonal best: 3 min 49.2 s +/- 3.2 s) were assessed
      during the second lap of a 1500-m race. Their running kinematics was then
      compared with those of five elite runners (seasonal best: 3 min 35.6 s +/- 2.6 s)
      analysed during the second lap of the men's 1500-m final at the 2005 World
      Championships. Data were collected using two high-speed cameras operating at 200
      Hz with a three-dimensional pan and tilt system. Running speed was the same for
      both groups. Despite the similar contact times, the minimum knee angle during the
      stance phase was greater and the average extension velocity of the knee angle in
      the same phase slower in the elite runners than in the national-standard runners.
      In addition, the running technique of the elite runners appears to be
      characterized by a more efficient function of the hip joint. In conclusion, elite
      runners may utilize elastic energy more effectively, which, in combination with
      minimum concentric work, leads to improvements in their running performance.

PMID- 19391491
TI  - Variability in baseball pitching biomechanics among various levels of
      competition.
AB  - The aim of this study was to compare within-individual variability in baseball
      pitching among various levels of competition. It was hypothesized that
      variability decreases as level of competition increases. Five fastballs were
      analysed for 93 healthy male baseball pitchers (20 youth, 19 high school, 20
      college, 20 Minor League, and 14 Major League level pitchers). Eleven kinematic,
      four temporal, and six kinetic parameters were quantified with a 240-Hz automated
      digitizing system. Three multiple analyses of variance were used to compare
      individual standard deviations for kinematic, temporal, and kinetic parameters
      among the five competition levels. There was a significant overall difference in
      kinematics and in six of the eleven kinematic parameters analysed: foot
      placement, knee flexion, pelvis angular velocity, elbow flexion, shoulder
      external rotation, and trunk forward tilt. Individual standard deviations tended
      to be greatest for youth pitchers, and decreased for higher levels of
      competition. Thus pitchers who advanced to higher levels exhibited less
      variability in their motions. Differences in temporal variation were non
      significant; thus variability in pitching coordination was not improved at higher
      levels. Differences in kinetic variation were non-significant, implying no
      particular skill level has increased risk of injury due to variation in joint
      kinetics.

PMID- 19391492
TI  - Biomechanical analysis of circles on pommel horse.
AB  - The aim of this study was to analyse the principal mechanics of circles.
      Seventeen university male gymnasts performed circles on an instrumented pommel
      horse model that enabled the pommel reaction forces to be recorded at 1000 Hz
      with two force plates. The circles were also videotaped using two digital video
      cameras operating at 60 frames per second. During circles, the vertical component
      of the reaction forces peaked in the double-hand support phases. Changes in the
      velocity of the centre of mass corresponded to the change in the tangential
      components of horizontal reaction forces. The velocity of the centre of mass had
      its peaks in the single-hand support phases and its local minimums in the double
      hand support phases. The velocity of the ankles and that of the centre of mass of
      the head and trunk were minimal in the single-hand support phases and were
      maximal in the double-hand support phases. These results suggest that the circles
      were composed of vertical movements and two kinds of rotations: rotation of the
      centre of mass and rotation of the body itself about the centre of mass. These
      two kinds of rotations, which influence the legs' rotational velocity, are phase
      dependent. To further our understanding of circles, research on circles in
      different orientations on the pommel horse will be beneficial.

PMID- 19391493
TI  - Optimization of the felge on parallel bars.
AB  - The felge, or undersomersault, on parallel bars has become an important skill in
      men's artistic gymnastics as it forms the basis of many complex variations. To
      receive no deductions from the judges, the felge must be performed without
      demonstrating the use of strength to achieve the final handstand position. Two
      male gymnasts each performed nine trials of the felge from handstand to handstand
      while data were recorded using an automatic motion capture system. The highest
      and lowest scoring trials of each gymnast, as determined by four international
      judges, were chosen for further analysis. The technique used by each gymnast was
      optimized using a computer simulation model so that the final handstand position
      could be achieved with straight arms. Two separate optimizations found different
      techniques identified in the coaching literature that are used by gymnasts.
      Optimum simulations resulted in improved performances through a combination of
      increased vertical velocity and height of the mass centre at release. Although
      the optimum technique found close to the gymnasts' own technique was more
      demanding in terms of the strength required, it offered the potential for more
      consistent performance and future developments in skill complexity.

PMID- 19391494
TI  - Perception of self-selected running speed is influenced by the treadmill but not
      footwear.
AB  - In this study, we examined whether self-selected overground running speed was
      consistent (1) with perceived overground speed on the treadmill and (2) among
      barefoot and three footwear conditions. Participants ran across a 20-m runway 10
      times for each overground condition, with running speed calculated from kinematic
      data. For the treadmill condition, the participants were instructed to run at a
      speed that felt similar to their overground speed. This treadmill speed was
      chosen upon perception, with the display covered from the participant's view.
      Repeated-measures analysis of variance was used to detect differences in speed
      between overground and treadmill running, and also among barefoot and footwear
      conditions. Coefficient alpha (alpha) was calculated to determine repeatability
      of observations in each overground condition. The speed was higher during
      overground (3.65 +/- 0.40 m/s) than treadmill (2.25 +/- 0.75 m/s) running but did
      not differ among the barefoot and the three footwear conditions. Overall,
      overground speed was highly repeatable within an individual (alpha = 0.96-0.98).
      Researchers might consider using self-selected speed when investigating
      overground running mechanics with different foot-ground interface conditions. The
      influence of treadmill on the perception of speed may be related to shear force,
      running duration, joint load control, and/or other psychological factors.

PMID- 19391495
TI  - A computational method for analysis of underwater dolphin kick hydrodynamics in
      human swimming.
AB  - We present a new method that combines the use of laser body scans, underwater
      video footage, software-based animation, and a fully unsteady computational fluid
      dynamics technique to simulate and examine the hydrodynamics of the dolphin kick.
      The focus of the current work is to model this particular stroke in all its
      complexity with minimal ad-hoc assumptions or simplifications. Simulations of one
      female and one male swimmer (both at about 1.7 m beneath the water surface) at
      velocities of 0.95 and 1.31 m/s and Strouhal numbers of 1.21 and 1.06
      respectively are presented. Vorticity and fluid velocity profiles in the wake are
      examined in detail for both swimmers. A three-dimensional vortex ring is clearly
      identified in the wake for one of the cases and a two-dimensional slice through
      the ring corroborates previous experiments of Miwa et al. (2006). We also find
      that most of the thrust is produced by the feet and in both cases the down-kick
      produces much larger thrust than the up-kick.

PMID- 19391496
TI  - A cervical spine model to predict injury scenarios and clinical instability.
AB  - A complete and detailed three-dimensional finite element model of the human
      cervical spine (C1-C7), including soft and hard tissues, was created using a
      digitized geometric measurement tool. The model was validated against existing
      experimental studies in flexion, extension, lateral bending, and axial rotation.
      The aims of this study were to use the model to simulate the mechanisms of injury
      scenarios, such as diving and football accidents, and to correlate the external
      and internal responses of the spinal components to disc herniation and clinical
      instability. It was determined that a shear-generated flexion moment of about 10
      Nm or a compression-flexion load of 450 N would generate significant stresses and
      strains in the discs, together with sufficient posterior-anterior displacement
      and rotational angulation of the vertebrae, to place the mid and lower cervical
      spine at risk of clinical instability or disc herniation. The results revealed
      that the location of the maximum stresses in the discs could not be directly
      correlated with the type of loads. In addition, for the loadings considered, the
      maximum displacement of the spine could be reduced by as much as 50% when the
      restraint of the cervical spine is changed from a C7-T1 to C7-T1 and C1-C2 fixed
      conditions.

PMID- 19391497
TI  - Significant and meaningful effects in sports biomechanics research.
AB  - Errors in statistical analysis of multiple dependent variables and in documenting
      the size of effects are common in the scientific and biomechanical literature. In
      this paper, I review these errors and several solutions that can improve the
      validity of sports biomechanics research reports. Studies examining multiple
      dependent variables should either control for the inflation of Type I errors
      (e.g. Holm's procedure) during multiple comparisons or use multivariate analysis
      of variance to focus on the structure and interaction of the dependent variables.
      When statistically significant differences are observed, research reports should
      provide confidence limits or effect sizes to document the size of the effects.
      Authors of sports biomechanics research reports are encouraged to analyse and
      present their data accounting for the experiment-wise Type I error rate, as well
      as reporting data documenting the size or practical significance of effects
      reaching their standard of statistical significance.

PMID- 19391498
TI  - [Directions of investigations for new drugs in asthma].
AB  - Bronchial asthma is affecting more than 300 million people worldwide and in every
      15-20 years additional 100 million patients are expected. About 5-10% of
      asthmatic patients have severe disease and fails to respond to conventional
      therapy. For this reason a new therapy or improvement in available treatment are
      under investigations. More knowledge of asthma mechanisms has led to monoclonal
      antibody, inhaled anti-oxidants and new combination therapy with corticosteroids.
      Similarly, biological agents directed against IL-13 and immunomodulators
      influenced T-regulatory cells are likely to be successful in the future therapy.

PMID- 19391499
TI  - [Gene of platelet/endothelial cell adhesion molecule 1 expression profile in
      patients with acute coronary syndrome and in healthy subjects performed in
      peripheral blood mononuclear cells using quantitative QRT-PCR reaction].
AB  - Cardiovascular diseases including myocardial infarction cause 50 percent of all
      deaths cases and range before cancer as the cause of death. The term 'ischemic
      heart disease' covers wide range of diseases including all ischemic conditions of
      myocardium. It's the most common reason (98%) is atherosclerosis, which causes a
      restriction or occlusion of a coronary artery lumen resulting in myocardial
      ischemia. Acute coronary syndromes are caused by the rupture of unstable
      atherosclerotic plaque resulting in clot formation which blocks the blood vessel.
      In this process an important role play adhesion molecules triggering adhesion,
      aggregation and the whole blood coagulation cascade. AIM OF THE STUDY: The aim of
      the study was to assess PECAM-1 gene expression in peripheral blood mononuclear
      cells in patients with acute coronary syndrome during first 24 hours of
      hospitalization in comparison with healthy individuals. MATERIAL AND METHODS:
      There were 80 subjects included to the study divided into two groups. First
      group, consecutive patients admitted to the Department of Cardiology due to acute
      coronary syndrome and the second group, 20 healthy subjects. The total RNA was
      extracted from peripheral blood mononuclear cell (PBMC) using Chomczynski and
      Scchaci method. Transcription activity was assessed using commercially available
      TaqMan Gene Expression Assays. The PECAM-1 gene PCR reaction was preformed with
      ABI PRISM 7000 Sequence Detector (Applied Biosystems, USA). RESULTS: The
      comparison of PECAM-1 gene expression revealed statistically significant
      difference, between increased level of PECAM-1 in patients with acute coronary
      syndrome and it's lower level in healthy individuals. CONCLUSION: Observed in
      peripherial blood mononuclear cells increase of PECAM-1 protein gene expression
      may be responsible for increased adhesion and aggregation process and acute
      coronary syndrome occurrence.

PMID- 19391500
TI  - [Cytometric evaluation of immaturity granulocytes in infections].
AB  - The leukocyte differential count is one of the most useful and frequency
      requested tests in the clinical laboratory. Conventional blood cell counting
      instruments can enumerate only the WBCs normally found in the peripheral blood,
      i.e., neutrophils, lymphocytes, monocytes, eosinophils, and basophils.
      Nevertheless, there are other cells not normally found in the peripheral blood,
      such as immature granulocyte. They are indicators of different disease states. We
      haven't got still references of automatic method to good evaluation of
      enumeration of the immature granulocyte. AIM OF THE STUDY: The aim of this study
      was compare count immature granulocytes by manual microscopy method with flow
      cytometric method. Flow cytometric method enumeration of immature granulocyte was
      performed using monoclonal antibody: anti-CD45, anti-CD11b and anti-CD16.
      RESULTS: A comparison of flow cytometry count with the manual count of
      promyelocytes, myelocytes, and metamyelocytes using linear regression revealed a
      correlation coefficient of 0,85 for percentage counts. CONCLUSIONS: Our results
      indicate that the flow cytometric immature granulocyte count can replace the
      manual morphology count for the laboratory work.

PMID- 19391501
TI  - [Impact of pegylated interferon alpha and ribavirin therapy of chronic hepatitis
      C on peripheral blood and intrahepatic lymphocytes].
AB  - The role of cellular immune response in pathogenesis of liver cell injury and
      course of chronic hepatitis C have been previously confirmed. The aim of this
      study was to determine the modification of T-lymphocyte subsets during pegylated
      interferon alpha (PegIFN) and ribavirin treatment and its correlation with
      response to the treatment. MATERIAL AND METHODS: The assessment of subsets of
      intrahepatic lymphocytes and peripheral blood lymphocytes was done in 62 patients
      with chronic hepatitis C using flow cytometry and immunohistochemical method.
      RESULTS: Significant increase in peripheral blood CD4+ cells, was observed in
      week 12 of treatment in patients with both complete and partial response to
      therapy. There were no significant modifications in nonspecific CD8+ subsets, but
      after 12 week of treatment in patients with response to therapy, decrease or lack
      of HCV-specific CD8+ cells were observed. The assessment of subsets of
      intrahepatic lymphocytes revealed a significantly higher percentage of CD8+ cells
      in pretreatment liver biopsies from patients with sustained viral response.
      CONCLUSIONS: The results confirmed the impact of interferon alpha and ribavirin
      treatment on cellular response. Some immunological host factors should be
      considered in the early prognosis of successful treatment.

PMID- 19391502
TI  - [The analysis of usefulness different diagnostic methods in children and
      adolescents with Helicobacter pylori infection].
AB  - A diagnostics of Helicobacter pylori infection in children and adolescents in
      practice sometimes is still difficult. Qualification to the tests for detecting
      infection with invasive and noninvasive methods should start from diligent
      anamnesis. THE AIM OF THE STUDY: Is to present the clinical course and results of
      diagnostic tests in children and adolescents with suspicion of Helicobacter
      pylori infection. MATERIAL AND METHODS: One hundred patients aged between 18
      months and 18 years who underwent endoscopy with gastric biopsies, histology,
      culture and 13carbon urea breath test. There were 36 boys and 64 girls in
      analysed group, 10% of them were preschool children, 42% school children and 48%
      teenagers older than 12 years RESULTS: Patients were symptomatic and most
      frequent were dyspeptic symptoms (91%). A symptom duration time was varied from
      several days to several years. On the basis of endoscopy and histology gastritis
      and/or duodenitis were found in 92 patients, esophagitis and gastritis in 5
      patients, duodenal ulcer in 2 patients, in 1 case gastric and duodenal mucosa was
      normal. Helicobacter pylori infection was histopathologically confirmed in 37
      patients. In 15 cases Helicobacter pylori strains were isolated with full in
      vitro sensitivity to amoxicillin, claritromycin and metronidazol. Urea breath
      test was conducted in 85 analyzed patients and 51 of them had abnormal result.
      CONCLUSIONS: In clinical picture of Helicobacter infection most frequent were
      dyspepstic symptoms and by endoscopy chronic gastritis and/or duodenitis were
      shown. Culture of Helicobacter pylori has a limited usefulness in practice
      especially in patients who underwent antibiotic/eradication therapy. The
      statistical significant concordance occurred between culture and noninvasive
      13carbon urea breath test.

PMID- 19391503
TI  - [Comparable efficacy between twice and three times daily for treatment of balance
      system disturbances].
AB  - In spite of detailed examinations it is impossible to find reasons for balance
      system disturbances in more than 25 per cent of patients. Therefore doctors have
      to treat symptoms but not the reasons for balance system disturbances. One of the
      most frequently administered medicine in treatment of both central and peripheral
      balance system disturbances is betahistine dihydrochloride (Betaserc). The aim of
      the study was to evaluate the influence of Betaserc an balance system
      disturbances with reference to dosage. MATERIAL AND METHODS: Patients were
      divided into two groups. The first group (Group I) was treated with Betaserc
      three times a day: 16 mg for minimum 4 weeks and 8 mg for minimum 8 weeks. The
      second group (Group II) was treated with Betaserc twice a day: 24 mg for maximum
      4 weeks and next 12 mg for minimum 8 weeks. The data from interviews and
      additional examinations (videonystagmography and posturography) were considered.
      RESULTS: The latter group more often showed smaller balance system disturbances
      and vertigo than the first group both after 4 and 12 weeks. After 12 weeks of
      treatment more patients from the second group reported "a complete disappearance"
      of the symptoms. A substantial improvement of results was observed in
      videonystagmography and posturography examinations. CONCLUSION: The treatment
      with 24 mg for 4 weeks and 12 mg for 8 weeks twice daily was better tolerated and
      gave higher positive effects than the treatment three times a day with 16 mg for
      4 weeks and 8 mg for 8 weeks.

PMID- 19391504
TI  - [The relation of atopy patch tests with immunoglobulin E. Atopy patch tests with
      aeroallergens results dependence with the concentration of specific class E
      antibodies assay level assessment].
AB  - Aeroallergens play an important role in atopic dermatitis (AD). This role is
      confirmed by widely used skin prick tests and total and specific class E
      antybodies levels assays. Atopy patch tests (APT) are a new diagnostic method.
      The aim of this study was to assess the correlation between APT results and
      specific class E antibodies levels. MATERIAL AND METHODS: 115 subjects with AD
      were examined. APT were done using a single allergen extract or their mix from
      commercially available reagents from Stallergenes (France). The determination of
      antigen specific IgE (sIgE) were done with fluoroimmunoenzymatic assay using
      Pharmacia CAP System FEIA set from Pharmacia-LKB (Sweden). RESULTS:
      Hyperreactivity to house dust mite mix was proved by APT in 45,2%, birch pollen
      in 32,2%, grass pollen mix in 22,6%, and cat dander in 15,7% of subjects.
      Increased level of sIgE against house dust mite allergens were proven in 42,6%,
      against birch pollen allergens in 30,3%, against grass pollen mix allergens in
      43,1% and against cat dander allergens in 31,8% of examined subjects. The
      correlation between positive APT results and increased specific IgE levels was
      not statistically significant. The intensification of positive APT reactions was
      correlated positively with the specific IgE levels of allergens against house
      dust mite, birch pollen, and cat dander. CONCLUSION: Conducted studies are
      indicating that APT can be an usefull AD diagnostic tool and are complementing
      all existing methods.

PMID- 19391505
TI  - [The quality of life after the surgery of laryngeal or hypopharynx neoplasms].
AB  - The number of diagnosed instances of larynx and laryngopharynx cancer is
      systematically increasing in Poland, especially in men. Advanced stage of the
      primary tumour and metastases to the lymph nodes result in the necessity of total
      laryngectomy. Serious disease, disability connected with extensive surgery and
      uncertain prognosis influence further professional career and personal
      relationships of the patients. The aim of this paper is to assess the life of
      patients after surgery for larynx or laryngopharynx cancer. MATERIAL AND METHODS:
      The analysis involved 92 patients after total laryngectomy due to squamous cell
      carcinoma. A significant majority of the patients (59%) judged their lifestyle
      before surgery as reprehensible. They attributed it to alcohol abuse (95%), heavy
      smoking (94%), exposure to harmful environmental conditions (73%) and to harmful
      conditions at workplace (51%). RESULTS: After treatment, which was accepted by
      over 95% of the patients, many of them quit using alcohol (57%) and quit smoking
      (75%). Because of serious health condition and difficult economic situation, only
      a few of them decided to change their working or living conditions. 46% of
      patients judged that after undergoing complete treatment, the quality of their
      life deteriorated. However, their awareness of the health-threatening factors
      grew. CONCLUSIONS: Total laryngectomy in patients with larynx and laryngopharynx
      cancer deteriorates quality and working or living conditions. The disease causes
      patients' criticism of their lifestyle before operation. Only 16% of treated did
      not changed life style after larygectomy.

PMID- 19391506
TI  - [Neurological disorders in systemic lupus erythematosus patients].
AB  - Central nervous system involvement in systemic lupus erythematosus contributes to
      more serious course and poor prognosis. Whereas neuropsychiatric lupus is the
      scantiest recognized aspect of SLE. AIM OF THE STUDY: Assessment of neurological
      syndromes prevalence and its clinical features in patients diagnosed with
      systemic lupus erythematosus. MATERIAL AND METHODS: The study comprised a group
      of 44 in- and outpatients of the Department of Dermatology and Venerology of
      Medical University of Lodz diagnosed with systemic lupus erythematosus and
      treated in 2006-2007. Each patient was assessed by a neurologist, who took
      history, performed clinical, neurological examination and, if required,
      laboratory studies. Systemic lupus activity measure (SLAM) was employed for the
      assessment of the disease activity. Cumulative dose of administered
      corticosteroids was calculated retrospectively for each patient, according to
      medical history. RESULTS: High prevalence of neurological syndromes was observed
      in the examined group (77,27%). The most frequent was headache (38,64%).
      Cerebrovascular disease, prevalent among systemic lupus erythematosus patients
      (31,82%) was related to more active lupus course. Moreover in the examined group
      seizures (13,64%), mononeurpathy (13,64%), cognitive impairment (6,82%),
      polineuropathy (4,55%), cranial neuropathy (2,77%) and acute confusional state
      (2,27%) were diagnosed. Neurological syndromes were often the first manifestation
      of systemic lupus erythematosus. There was no relationship observed between the
      cumulative dose of glucocorticosteroids and the nervous system involvement.
      CONCLUSIONS: High prevalence of nervous system manifestation in SLE indicates the
      need for neurological care in SLE patients. Headache is frequent but low specific
      sign of neuropsychiatric lupus. Neurological disease should incline toward more
      intense immunosuppressive therapy which may delay the nervous system destruction.

PMID- 19391507
TI  - [The effect of COX-1 and COX-3 inhibitors on blood nitric oxide concentration].
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to different chemical groups
      and thus they can exert different effect on metabolism of biologically important
      substances. The aim of the study was to estimate the effect of two nonsteroidal
      anti-inflammatory drugs: COX-1 inhibitor - resveratrol (trans-3,4,'5
      trihydroxystilben) which is a diet supplement, and COX-3 inhibitor - paracetamol
      (acetaminophen) on blood nitric oxide (NO) concentration in experimental animals.
      MATERIAL AND METHODS: The examinations were performed in rats, that were
      administered resveratrol in a dose 2.5 and 10 mg/kg body weight and paracetamol
      in a dose 36 and 150 mg/kg body weight by an intragastric tube for three weeks.
      RESULTS: The results were compared with control animals that were administered
      water instead of the drugs. Nitric oxide was determined with the use of Nitric
      Oxide Non-Enzymatic Assay (Oxix International). CONCLUSION: In the applied
      experimental model, both paracetamol and resveratrol increased significantly
      nitric oxide concentration in blood.

PMID- 19391508
TI  - [In vitro biological activity of new platinum(II) and palladium(II) complex
      compounds].
AB  - A nitrogen ring is present in many biological molecules, which play an important
      part in cell division as well as in genetic information transfer. It is also a
      part of the purine system, which builds DNA and has potential places/spots of
      platinum drug co-ordination. Therefore, it may be hoped, that platinum(II)
      complexes with diazol ligands will have considerable affinity for DNA binding
      sites. The work was aimed at assessment of biological activity and especially of
      cytotoxic activity, of new complex connections of the selected diazols with
      Pt(II) and Pd(II) ions. MATERIALS AND METHODS: The MTT test is aimed at the
      assessment of cytotoxicity of chemical compounds. It consists in the colorimetric
      determination of a product--farmazon, formed after adding MTT (bromide 3[4,5
      dimetylo-2-ilo]-2,5-difenylotetrazolu) to the culture suspension in the presence
      of the compound subject to the test. All the tested Pt(II) complexes before
      adding to the cell cultures were dilluted in DMF. MTT tests for individual
      complexes were conducted on two cell lines L1210 and P388. RESULTS: Compounds 13,
      21 and 25 on P388 neoplastic cell revealed about three times smaller in-vitro
      cytotoxicity, whereas platinum(II) and palladium(II) complexes 13, 21, 25, 43,
      46, revealed cytotoxicity being about 3-4 times smaller than the reference
      cisplatin. Complex 45 revealed eight times smaller activity and complex 44
      revealed significantly small, about two hundred smaller activity. CONCLUSION:
      Based on the MTT tests it may be concluded that compounds 13, 21 and 25 reveal
      selective cytotoxicity to P388 neoplastic cells.

PMID- 19391509
TI  - [Testing antineoplastic activity of new platinum(II) and palladium(II) complex
      compounds].
AB  - A pyrazole system is incorporated in many biological molecules which play an
      important part in genetic processes. It seems that co-ordinating biological
      molecules, which would serve as carriers, should contribute to minimising the
      toxic effects of the potential platinic drugs. AIM OF THE STUDY: Assessment of in
      vivo biological activity, and in particular of antineoplastic activity of new
      platinum(II) and palladium(II) complexes. MATERIAL AND METHODS: The assessment of
      toxicity of the compounds was made with the Deichmann and Le Blanck method. The
      antineoplastic activity of the new complex compounds--pyrazole derivatives with
      Pt(II) and Pd(II) ions was tested on mouse L1210 leukemia cell culture and on
      lymphatic leukemia P388. BDF1 or CDF1 mice divided into groups of 5-9 animals
      were subject to the tests. RESULTS: Complexes 13, 21, 25, 16, 24 and 28 did not
      reveal any antineoplastic activity to the mouse L1210 leukemia, whereas complexes
      13, 21 and 25 revealed in-vivo antineoplastic activity to the P388 leukemia,
      extending the mouse's survival time by about 50%. The control group consisted of
      mice which were administered a 14% methylcellulose solution. CONCLUSIONS: As a
      result of the tests conducted to asses the in-vivo antineoplastic activity it was
      found that the 25 complex demonstrates the strongest activity to the P388
      leukemia. It may be presumed that it is caused by trans configuration of the
      complex predisposing to the creation of interstrand cross-links. It may be also
      caused by the presence of the chloromethyl substituents, located on N1 nitrogen
      atom of the ligand, which increases the capacity of nitrogen N7 guanine
      alkylation in DNA.

PMID- 19391510
TI  - [Successful treatment of severe hypertriglyceridemia with plasmapheresis--case
      report].
AB  - Presented case report shows hypertriglycerydemia treatment problem in 26-year-old
      woman with 2 episodes of acute pancreatitis history. Very high serum
      triglycerides concentration and clinical symptoms suggested chylomicronemia
      syndrome with urgent need for treatment. After a course of several subsequent
      therapeutic plasmapheresis triglycerides significantly decreased. Safety and
      effectiveness of this method was confirmed.

PMID- 19391511
TI  - [Primary testical lymphoma].
AB  - In our report we present a rare case of primary non Hopdgkin lymphoma of the
      testis in 70-years-old man, who was diagnosed and treated from syderopenic
      anemia. Here we demonstrate difficulties with differential diagnosis mentioned
      tumor.

PMID- 19391512
TI  - [The diagnostic and healing difficulty at "patient" with Klinefelter's syndrome,
      the disorders of the personality of the type borderline, the eating disorders and
      mixed dependence from the drugs].
AB  - It was described the case of 25-years-old person's dependent from medicines
      (reassuring, sleeping and analgesic)and alcohol from coexisting rare disorders
      happened in the detox squad. Establish that person, during the treatment metrical
      he is the man and possesses the characteristic genotype for the Klinefelter's
      syndrome, the features of the personality of type borderline and the eating
      disorders (bulimic side of annorexia). Her autobiography, psychical state (she
      underlined that he felt the woman despite the sex mentally by the whole time of
      the stay) her behavior are the interesting therapeutics problems. In the article
      was introduced the test explanation of mechanisms her psychical functioning, and
      the difficulty which appeared in the process of diagnosis and psychotherapy. The
      Klinefelter's syndrome was differentiated with transsexualism seldom in the aim
      of the more exact understanding of above mentioned difficulties. Medical and
      psychoterapeutic strategies were proposed for that person.

PMID- 19391513
TI  - [Erectile dysfunction, and risk factors of cardiovascular disease].
AB  - The paper is a review of the reports presenting the essential aspects of erectile
      dysfunctions being a serious challenge for the clinicians of various
      specializations because of increasing number of the diagnosed cases of sexual
      impairments caused by atherosclerotic background. The authors present the results
      of the most crucial studies concerning epidemiology of the said condition, an
      effect of the various demographic factors on its occurrence, with the focus laid
      on the significant correlation between classic risk factors of atherosclerotic
      cardiovascular disease and reasons leading to erectile dysfunctions. The work
      presents also the diagnostic and therapeutic obstacles, the physicians struggling
      with this more and more often disease, encounter in their every day practice.

PMID- 19391514
TI  - [Can obstructive bronchitis be a risk factor of bronchial asthma in infants and
      small children?].
AB  - One of more frequent reasons for hospitalizations concerning infants and small
      children are obstructive bronchitis. Great prevalence of bronchial tree
      obturation during infancy and in small children is a result of anatomical and
      functional differences of airways and immunological differences that occur in
      infants and small children. The most frequent cause of bronchial tree obturation
      is infection induced by viruses, rarely by bacteria. Recurrences of bronchial
      tree obturation are observed in some patients. Obturation recurrences can be
      caused by number of diseases that appear during infancy and in small children,
      for example cystic fibrosis of the pancreas. Also the presence of foreign body in
      the airways, immotile cilia syndrome, immunological disturbances, innate
      anomalies of the respiratory system and the circulatory system and bronchial
      asthma can result in obturation recurrences. Various clinical criteria are
      established and new markers of allergic inflammation are searched in view of
      difficulties to diagnose bronchial asthma in the youngest children. There are no
      unequivocal rules to diagnose bronchial asthma in infants and small children
      despite these searches.

PMID- 19391515
TI  - [Epidemiology and risk factors of the esophageal squamous cell carcinoma].
AB  - Esophageal carcinoma is the eighth most common malignancy in the world. In most
      countries, including Poland, the squamous cell carcinoma is a predominant
      histological type. It is characterized by extreme diversity in geographical
      distribution and incidence. High incidence is noted in regions located along with
      so-called "Asian esophageal cancer belt" beginning from eastern Turkey through
      Caspian littoral countries, northern Afghanistan to Central and Eastern Asia, as
      well as in Japan, South Africa and some South American countries. In Western
      Europe the highest incidence is observed in France, Portugal and northern Italy.
      Poland belongs to low-incidence countries with the age-standardized annual
      incidence exceeding 4.5 and 0.7/100,000, for men and women respectively. Etiology
      of the cancer is multi-factorial. In western countries the most important risk
      factors are tobacco smoking and alcohol consumption, and to a lesser extent, an
      inappropriate diet. In other countries, a diet lacking of fresh vegetables and
      fruits with vitamin and mineral deficiency and high level of sodium chloride,
      carbohydrates and animal fats is a predominant factor. Furthermore, preserving
      and processing food which facilitates accumulation of carcinogens, special
      dietary habits and viral infections are also attributed to the development of
      cancer. More recently, the significance of genetically determined increased
      susceptibility of some individuals versus environmental factors has been
      stressed. Previous studies proved the relationship between cancer susceptibility
      and polymorphisms in genes encoding some important molecules engaged in
      carcinogens metabolism or DNA repair.

PMID- 19391516
TI  - [Lentigines in different multiple organ defects syndromes].
AB  - The aim of our study is to introduce a larger number of doctors to the subject of
      lentigines. They may be a first syndrome coexistent with very rare multiple organ
      defects as syndrome Peutz-Jeghers, LEOPARD, LAMB and Carney syndrome.

PMID- 19391517
TI  - [Vicious circle vs. virtuous circle: how to keep Revista Argentina de
      Microbiologia in the Science Citation Index Expanded].

PMID- 19391518
TI  - [Characterization of the Helicobacter pylori vacuolating cytotoxin gene in
      gastric biopsy specimens from patients living in Tolima, Colombia].
AB  - Helicobacter pylori successfully colonizes the gastric niche. These bacteria
      produce a vacuolating cytotoxin known as VacA, which is codified by the vacA
      gene. This protein represents an important virulence factor. H. pylori strains
      have different vacA alleles, which show a variety of phenotypes that have been
      associated with gastrointestinal diseases. The aim of this study was to generate
      data about the prevalence of H. pylori and the vacA genotype in Tolima (Colombia)
      residents, and to evaluate if there exists a relationship between these data and
      the development of different gastrointestinal pathologies. Seventy three patients
      with different pathologies were included. The DNA extracted from biopsy specimens
      was analyzed and the presence of bacteria was determined by amplifying a fragment
      of the 16 rDNA gene. The vacA genotype was also determined by PCR. Fifty-two
      percent out of the 50 genotyped samples showed vacA s1m1 allele, 42% vacA s2m2,
      4% s1m2, and 2% s1,s2,m1,m2. A higher sensitivity for the detection of H. pylori
      was evidenced by amplifying the vacA gene rather than the 16S rDNA gene. No
      association was found between the vacA genotype and the gastrointestinal diseases
      included in the study.

PMID- 19391519
TI  - [Characterization of Vibrio cholerae non-O1 and non-O139 isolates associated with
      diarrhea].
AB  - Vibrio cholerae, etiologic agent of cholera, is transmitted to humans by
      ingestion of contaminated food or water. Even though serogroups O1 and O139 are
      the ones usually associated to epidemic cholera, isolates from other serogroups
      also cause gastroenteritis and extraintestinal infections. During the period 2003
      2005, presence of V. cholerae in stools was investigated in children with
      diarrhea that seaked assistance at the Nino Jesus Hospital in Tucuman. Thirty
      four isolates of V. cholerae non-O1, non-O139 were recovered. We characterized
      the isolates studying its virulence factors by PCR, antimicrobial susceptibility
      patterns and genetic diversity by pulsed-field gel electrophoresis. Eight
      virulence patterns were obtained although no isolate was positive for the cholera
      toxin or the thermostable toxin. Four isolates were positive for the type three
      secretion system. The 17.6% of the isolates were resistant or intermediate to
      ampicillin and 5.9% were resistant to trimethoprim-sulfamethoxazole. By Sfil
      PFGE, all isolates were genetically very diverse, as 27 different patterns were
      identified in 29 typeable isolates by pulsed-field gel electrophoresis. Although
      it has a low incidence, V. cholerae continues to be a causative agent of diarrhea
      in children, who are affected by a variety of circulating strains of V. cholerae
      non-O1, non-O139.

PMID- 19391520
TI  - [Molecular diagnosis of human histoplasmosis in whole blood samples].
AB  - To assess the value of using whole blood samples for the molecular diagnosis of
      histoplasmosis, we applied an in-house DNA extraction method and a nested PCR
      targeting a 210 bp specific segment of the Histoplasma capsulatum HcP100 gene. A
      whole blood volume of 2.5-3 milliliters was centrifuged and the cellular pellet
      was treated with Trichoderma harzianum lyticase and proteinase K prior to
      applying a conventional phenol DNA extraction. This procedure allowed complete
      cell lysis, high DNA yield and specific amplification. The PCR detection limit
      was 0.25-1 yeast cells/ml of blood sample. The method was assessed on 31 blood
      samples from 19 patients with microbiological diagnosis of histoplasmosis, 30
      healthy persons and 21 patients with other mycoses or mycobacterial diseases.
      Positive results were obtained in samples from 17/19 patients with histoplasmosis
      (14/15 immunocompromised and 3/4 without known immunological disorder). Blood
      samples from the 30 healthy controls and 20 patients with other conditions proved
      negative; the only false positive result was obtained from a patient with
      Mycobacterium avium-intracellulare infection. With 89% sensitivity and 98%
      specificity, this molecular method for detection of the agent in blood shows
      promising for the rapid diagnosis of human histoplasmosis.

PMID- 19391521
TI  - [Sporotrichosis in a domestic cat].

PMID- 19391522
TI  - [Toxocara canis under the microscope].

PMID- 19391523
TI  - Prevalence of mef and ermB genes in invasive pediatric erythromycin-resistant
      Streptococcus pneumoniae isolates from Argentina.
AB  - During the period 1993-2001, a total of 1,499 pneumococci isolates were recovered
      through the Argentinean surveillance of Streptococcus pneumoniae causing invasive
      disease in children under 6 years of age, 3.5% of which were erythromycin
      resistant. Among the 50 erythromycin-resistant strains available, 58% (n=29)
      harbored mefA/E genes (15 mefA, 30%; and 14 mefE, 28%), 34% (n=17) ermB, and 6%
      (n=3) both mefA/E plus ermB genes, while one isolate was negative for all the
      acquired genes studied. The England14-9 (42%), Poland6B-20 (20%) and Spain9V-3
      (16%) clones were responsible for the emergence of pneumococcal macrolide
      resistance in pediatric population from Argentina.

PMID- 19391524
TI  - [Linezolid for the treatment of newborns infected with vancomycin-resistant
      Enterococcus faecium].
AB  - Five patients hospitalized in the neonatal unit between 2002 and 2007, infected
      with vancomycin-resistant Enterococcus faecium treated with linezolid are
      presented in this study. This antibiotic showed good clinical efficacy and
      safety, since no adverse events occured in this group of patients.

PMID- 19391525
TI  - Alterations in growth and branching of Neurospora crassa caused by sub-inhibitory
      concentrations of antifungal agents.
AB  - Six antifungal agents at subinhibitory concentrations were used for investigating
      their ability to affect the growth and branching in Neurospora crassa. Among the
      antifungals herein used, the azole agent ketoconazole at 0.5 microg/ml inhibited
      radial growth more than fluconazole at 5.0 microg/ml while amphotericin B at 0.05
      microg/ml was more effective than nystatin at 0.05 microg/ml. Morphological
      alterations in hyphae were observed in the presence of griseofulvin, ketoconazole
      and terbinafine at the established concentrations. The antifungal agents were
      more effective on vegetative growth than on conidial germination. Terbinafine
      markedly reduced growth unit length (GU) by 54.89%, and caused mycelia to become
      hyperbranched. In all cases, there was a high correlation between hyphal length
      and number of tips (r > 0.9). All our results showed highly significant
      differences by ANOVA, (p < 0.001, alpha = 0.05). Considering that the hyphal tip
      is the main interface between the fungus and its environment/through which
      enzymes and toxins are secreted and nutrients absorbed, it would not be desirable
      to obtain a hyperbranched mycelia with inefficient doses of antifungal drugs.

PMID- 19391526
TI  - Mycobacteriophages as versatile tools for genetic manipulation of mycobacteria
      and development of simple methods for diagnosis of mycobacterial diseases.
AB  - Tuberculosis, caused by Mycobacterium tuberculosis, is responsible for over two
      million deaths per year worldwide. Due to its long doubling time (18 h), the
      microbiological detection of M. tuberculosis by conventional methods takes up to
      one month, unless the number of bacilli in the biological sample is high enough.
      Thus, drug resistance assessment requires at least one month for obtaining the
      primary culture and another month to determine its susceptibility to
      antimycobacterial drugs. Moreover, for a long time, the lack of genetic tools for
      mycobacteria has been a barrier for undertaking studies aimed at understanding
      the mechanisms of drug resistance and drug target identification, being all these
      topics of utmost importance considering the increase in the number of drug
      resistant clones and the few therapeutic options available. Mycobacteriophages
      are promising as a novel source of genetic elements for mycobacteria
      manipulation, as well as for the development of versatile, simple, fast and cheap
      methods for drug resistance assessment of M. tuberculosis clinical isolates. We
      herein describe the background related to the use of mycobacteriophages, with
      emphasis placed on their utilization for drug resistance analysis in our country.

PMID- 19391527
TI  - ["First regulating vitality" is core of acupuncture].
AB  - In combination with long-term clinical practice of acupuncture and moxibustion,
      and repeatedly learn, comprehend and probe theoretical intension about "essence"
      and "vitality" of acupuncture in Neijing (Internal Classic) to guide clinical
      practice. By the regulative mechanisms of needling "target points" of the
      peripheral nerve and central "target location", form single point therapy, rapid
      acupuncture, taking effect in three seconds, safety and other technique
      characteristics. Confirm that Deqi (needling sensation) is concrete reflection of
      "essence of acupuncture", regulating vitality (center) is the key of "first
      treating the vitality". The classical theory, "First treating vitality is essence
      for acupuncture" in Neijing, is correct and it is theoretical core of scientific
      acupuncture, which is of wide practical significance and profound historic
      significance for guiding clinical practice of acupuncture and moxibustion.

PMID- 19391528
TI  - [Clinical observation on moxibustion combined with intermittent urethral
      catheterization for treatment of neurogenic vesical dysfunction].
AB  - OBJECTIVE: To observe the effect of moxibustion combined with intermittent
      urethral catheterization on vesical function in the patient of neurogenic vesical
      dysfunction. METHODS: Seventy-six cases were randomly divided into an observation
      group and a control group, 38 cases in each group. The control group was treated
      with routine intermittent urethral catheterization and the observation group with
      the intermittent urethral catheterization and moxibustion on Guanyuan (CV 4),
      Mingmen (GV 4), Zusanli (ST 36), etc. Changes of residual urine volume, white
      cell count and the balance state of the urinary bladder were selected as the
      indexes of therapeutic effect and the therapeutic effects were compared between
      the two groups. RESULTS: The total effective rate was 97.4% in the observation
      group and 79.0% in the control group with a significant difference between the
      two groups (P < 0.05); after treatment, there were significant differences
      between the two groups in the residual urine volume, the bladder volume and the
      case numbers reaching to the functional balance state of bladder (all P < 0.05),
      and there was no significant difference between the two groups in white cell
      count change (P > 0.05). CONCLUSION: Moxibustion combined with intermittent
      urethral catheterization can significantly improve vesical function in the
      patient of neurogenic vesical dysfunction, reducing residual urine volume,
      increasing volume of bladder, promoting the balance state of vesical function,
      but it is basically same as intermittent urethral catheterization in prevention
      of urinary infection and therapeutic effect.

PMID- 19391529
TI  - [Controlled study of auricular point taping and pressing therapy for treatment of
      vascular dementia].
AB  - OBJECTIVE: To assess the therapeutic effect of auricular point taping and
      pressing therapy on vascular dementia (VD). METHODS: One hundred and eighty cases
      of vascular dementia were randomly divided into an auricular point taping and
      pressing group and a western medicine group, 90 cases in each group. The
      auricular point taping and pressing group was treated by auricular point taping
      and pressing at auricular points Shennen, Nao (brain), Shen (kidney), Zhen
      (pulvinal), and the western medicine group by oral administration of Nimodipine,
      thrice each day, 30 mg each time. They were treated for 12 weeks. The scores of
      mini-mental state examination (MMSE) and activities of daily living (ADL), and
      adverse reaction were observed. RESULTS: The scores of MMSE before treatment and
      12 weeks after treatment were 18.00 +/- 3.88 and 20.83 +/- 3.74 in the auricular
      point taping and pressing group, and 17.80 +/- 3.82 and 20.70 +/- 3.53 in the
      western medicine group, respectively, with significant increases in scores of
      MMSE after treatment in the two groups (both P < 0.01) and with no significant
      difference between the two groups (P > 0.05). The scores of ADL before treatment
      and 12 weeks after treatment were 44.90 +/- 14.84 and 39.60 +/- 12.45 in the
      auricular point taping and pressing group, and 45.70 +/- 14.86 and 39.10 +/-
      13.44 in the western medicine group, respectively, with significant decreases
      after treatment in the two groups (both P < 0.01) and with no significant
      difference between the two groups (P > 0.05). In the auricular point taping and
      pressing group, 2 cases withdrew from the test because adhesive plaster allergic
      reaction induced severe itch of the auricle. In the western medicine group, one
      case had mild dizziness and another case had diarrhea respectively. CONCLUSION:
      Auricular point taping and pressing and Nimodipine have similar therapeutic
      effect on vascular dementia, and have no obvious adverse reaction, except
      adhesive plaster allergic reaction.

PMID- 19391530
TI  - [Observation on therapeutic effect of acupuncture combined with chinese herbs on
      polycystic ovary syndrome of kidney deficiency and phlegm stasis type].
AB  - OBJECTIVE: To observe the clinical therapeutic effect of acupuncture combined
      with Chinese herbs on polycystic ovary syndrome of kidney deficiency and phlegm
      stasis type and probe into the mechanism. METHODS: Sixty-three cases of
      polycystic ovary syndrome of kidney deficiency and phlegm stasis type were
      randomly divided in to a combined acupuncture and Chinese herb group (n=32)
      treated with acupuncture at Qihai (CV 6), Guanyuan (CV 4), et al. and oral
      administration of Chinese herbs, and a simple Chinese herb group (n=31) treated
      with oral administration of the same Chinese herbs as in the combined acupuncture
      and Chinese herb group. The therapeutic effects and changes of follicle
      stimulating hormone (FSH), luteotropic hormone (LH), testosterone (T) and LH/FSH
      were compared between the two groups. RESULTS: The total effective rate was 93.8%
      in the combined acupuncture and Chinese herb group and 80.6% in the simple
      Chinese herb group, the former being significantly better than the latter (P <
      0.05). The decrease of T in the combined acupuncture and Chinese herb group was
      significantly su perior to that in the simple Chinese herb group (P < 0.01).
      CONCLUSION: Acupuncture combined with Chinese herb therapy is superior to the
      simple Chinese herb in the clinical therapeutic effect on polycystic ovary
      syndrome of kidney deficiency and phlegm stasis type and decrease of T level,
      indicating this method is a better one for polycystic ovary syndrome of kidney
      deficiency and phlegm stasis type.

PMID- 19391531
TI  - [Study on SHI's Bian stone comprehensive therapy for rehabilitation after induced
      abortion].
AB  - OBJECTIVE: To explore the rehabilitation effect of SHI's Bian stone comprehensive
      therapy on the patient after induced abortion. METHODS: Thirty cases of induced
      abortion were treated with SHI's Bian stone comprehensive therapy in peri
      operative period. Before the operation, scraping therapy was given at the parts
      of The Urinary Bladder Channel and The Governor Vessel on the back and 30 min
      after the operation, the patient took a rest in a horizontal position on a mild
      heat Bian stone blanket and hot compress with a Bian stone plate was given at the
      lower abdomen. They received thrice return visits respectively on 1, 2, 3 weeks
      after the operation and SHI's Bian stone comprehensive therapy, including warm
      massage on The Governor Vessel, scraping the channel, patting Baliao (BL 31, BL
      32, BL 33, BL 34), penetration needling Sanyinjiao (SP 6), oblique needling Qihai
      (CV 6), Guanyuan (CV 4), Zhongji (CV 3), Zigong (EX-CA 1), and the Bian stone
      plate was placed on the needle hand for warm compress. Colporrhagia, menstrual
      return, soreness of waist and other symptoms after the operation were observed.
      RESULTS: After SHI's Bian stone comprehensive therapy, in the patient of induced
      abortion the colporrhagia volume was less within 3 days after the operation and
      the colporrhagia stopped more early; of the 30 cases, only 2 has soreness of
      waist, abdominal pain, fearing cool and other symptoms, and only one case had
      obviously delayed mestrual cycle. CONCLUSION: SHI's Bian stone comprehensive
      therapy used in peri-operative period of induced abortion has a good promoting
      action on post operative rehabilitation.

PMID- 19391532
TI  - [Observation on electroacupuncture combined with routine western medicine therapy
      for promoting consciousness of the patient with coma caused by craniocerebral
      trauma].
AB  - OBJECTIVE: To observe the promoting consciousness effect of electroacupuncture
      combined with routine western medicine therapy on the patient with coma caused by
      craniocerebral trauma. METHODS: Thirty-two cases were randomly divided into an
      acupuncture-medication group treated with electroacupuncture at Neiguan (PC 6)
      and Quze (PC 3) and routine western medicine, and a control group treated with
      routine western medicine, 16 cases in each group. Glasgow (GCS) scores were
      assessed after treatment for 7 sessions and 30 sessions respectively and the
      promoting consciousness rate was observed. RESULTS: After treatment of 7
      sessions, GCS score was 6.88 +/- 1.63 in the acupuncture-medication group and
      5.25-1.65 in the control group with a significant difference between the two
      groups (P < 0.05); after treatment of 7 sessions, the promoting consciousness
      rate was 25.0% in the acupuncture-medication group and 0 in the western medicine
      group, and after treatment for 30 sessions, the promoting conscious ness rate was
      81. 3% in the acupuncture-medication group and 43.8% in the western medicine
      group with a signifi cant difference between the two groups (P < 0.05).
      CONCLUSION: Electroacupuncture at Neiguan (PC 6) and Quze (PC 3) combined with
      western medicine has a good promoting consciousness effect in the patient with
      coma caused by craniocerebral trauma, which is better than that of simple western
      medicine.

PMID- 19391533
TI  - [Observation on therapeutic effect of pecking moxibustion of specific acupoints
      for treatment of irritable bowel syndrome (diarrhea type)].
AB  - OBJECTIVE: To compare therapeutic effects of pecking moxibustion therapy and
      common acupuncture on irritable bowel syndrome (diarrhea type). METHODS: Fifty
      cases of irritable bowel syndrome were randomly divided into a pecking
      moxibustion group (n=30) and an acupuncture group (n=20). The pecking moxibustion
      group was treated by pecking moxibustion with a ZHOU's pecking moxibustion pen,
      and the acupuncture group by common acupuncture. In the two groups, Ganshu (BL
      18), Pishu (BL 20), Weishu (BL 21), Shenshu (BL 23), etc. were selected. After
      treatment of 15 sessions the scores of symptoms and clinical therapeutic effects
      were compared between the two groups. RESULTS: After treatment, the scores of
      symptoms significantly decreased (both P < 0.01), with a significant difference
      in the decrease of symptom scores between the two groups (P < 0.05); the total
      effective rate of 93.3% in the pecking moxibustion group was higher than 75.0% in
      the acupuncture group (P < 0.05). CONCLUSION: Pecking moxibustion therapy can
      significantly improve the clinical symptoms of irritable bowel syndrome (diarrhea
      type), with a better therapeutic effect than common acupuncture.

PMID- 19391534
TI  - [Clinical study on scalp acupuncture with long needle-retained duration for
      treatment of Tourette syndrome].
AB  - OBJECTIVE: To observe therapeutic effects of different needle-retained durations
      at scalp acupoints on Tourette syndrome (TS). METHODS: Sixty-two cases of TS were
      randomly divided into an observation group and a control group, 31 cases in each
      group. In the observation group, the needles were retained for 2 h and in the
      control group, they were retained for 30 min. The middle line of forehead, middle
      line of vertex and lateral line 1 of vertex were selected as main acupoints, and
      anterior oblique line of vertex-temporal and posterior temporal line were
      selected as adjuvant acupoints. They were treated for 2 months, once other day.
      Yale Global Tic Severity Scale (YGTSS) and Tourette Syndrome Global Scale (TSGS)
      were used for assessment of therapeutic effects and their therapeutic effects
      were compared. RESULTS: After treatment, YGTSS and TSGS scores had very
      significant changes in the two groups as compared with those before treatment
      (both P < 0.01), indicating an obvious improvement in kinetic Tic and vocalizing
      Tic. The total effective rate was 61.3% in the observation group and 67.7% in the
      control group with no significant difference between the two groups (P > 0.05).
      CONCLUSION: Scalp acupuncture therapy of both 2 h and 0.5 h retaining needle can
      significantly improve symptoms of TS patients, with a similar therapeutic effect.

PMID- 19391535
TI  - [Observation on therapeutic effect of acupuncture, moving cupping and blood
      letting puncture on chloasma].
AB  - OBJECTIVE: To compare therapeutic effects of acupuncture, moving cupping, blood
      letting puncture and medicine on chloasma. METHODS: One hundred and seventy-six
      cases of chloasma were randomly divided into two groups. The acupuncture, moving
      cupping, blood-letting puncture group was treated with acupuncture at Ashi
      points, Xuehai (SP 10), Sanyinjiao (SP 6), moving cup at The Governor Vessel and
      The Urinary Bladder Channel on the back and then blood-letting puncture at Dazhui
      (GV 14), Feishu (BL 13), Geshu (BL 17), Xinshu (BL 15), Ganshu (BL 18) and nearby
      more severe purple stasis regions, and the medication group was treated with oral
      administration of Vit E and Vit C. Their therapeutic effects were observed after
      3 courses. RESULTS: The total effective rate was 96.7% in the acupuncture, moving
      cupping, blood-letting puncture group and 51.2% in the medication group with a
      significant difference between the two groups (P < 0.05). CONCLUSION: The
      therapeutic effect of acupuncture, moving cupping, blood-letting puncture on
      chloasma is better than that of the medicine.

PMID- 19391536
TI  - [Observation on therapeutic effect of electroacupuncture plus blood-letting
      puncture at Weizhong (BL 40) on acute lumbar disc herniation].
AB  - OBJECTIVE: To find a better method for treatment of acute lumbar disc herniation.
      METHODS: One hundred cases were randomly divided into 2 groups. The observation
      group of 52 cases was treated with electroacupuncture at Yaoyangguan (GV 3),
      Dachangshu (BL 25), Guanyuanshu (BL 26), Xiaochangshu (BI. 27) as main points,
      and blood-letting puncture at stagnant collaterals nearby Weizhong (BL 40); the
      control group of 48 cases was treated with traction combined with
      electroacupuncture at main points Jiaji (EX-B 2), Shenshu (BL 23), Dachangshu (BL
      25). Their therapeutic effects were observed and compared. RESULTS: The cured
      rate and the cured markedly effective rate were 55.8% and 82.7% in the
      observation group and 33.3% and 54.2% in the control group, respectively, with
      significant differences between the two groups (P < 0.05, P < 0.01). CONCLUSION:
      Electroacupuncture combined with blood letting puncture at stagnant collaterals
      nearby Weizhong (BL 40) has a signifi cant therapeutic effect on acute lumbar
      disc herniation.

PMID- 19391537
TI  - [Clinical observation on electroacupuncture at acupoints for treatment of senile
      radical sciatica].
AB  - OBJECTIVE: To compare therapeutic effects of electroacupuncture and TENS on
      senile radical sciatica. METHODS: One hundred and thirty-nine cases were randomly
      divided into 2 groups, electroacupuncture group (n=70) and TENS group (n=69). The
      electroacupuncture group was treated with electroacupuncture at main points
      Qihaishu (BL 24), Dachangshu (BL 25), Guanyuanshu (BL 26), etc. and the TENS
      group was treated with skin electrode sticking at the pressure pain point of the
      nerve trunk which was connected with pulse current. Their therapeutic effects
      were observed and compared. RESULTS: At the end of the first course, the cured
      rate was 41.4% in the electroacupuncture group and 29.0% in the TENS group with a
      significant difference between the two groups (P < 0.05), and at the end of
      second course, their cured rates were 80.0% and 44.9%, respectively, with a very
      significant difference between the two groups (P < 0.005). CONCLUSION: The
      therapeutic effect of electroacupuncture on senile radical sciatica is
      significantly better than TENS.

PMID- 19391538
TI  - [Specificity of acupoint effects and its fundamental laws].
AB  - The specificity of acupoint effects is the core of acupuncture theories and
      clinical practices. Based on summarization and analysis of ancient literature and
      contemporary research achievements by using data mining techniques, it is
      preliminarily held that the specificity of acupoint effects has its relativity
      and a certain law, which can be summarized as "course of meridian is the basis
      and confluence of meridian qi is the key", that is, the specificity of acupoint
      effects is closely correlated with the course of meridian and the confluence of
      meridian qi.

PMID- 19391539
TI  - [Effects of electroacupuncture on learning and memory ability and glial cells of
      the hippocampus in the rat of Alzheimer disease].
AB  - OBJECTIVE: To study on the mechanism of electroacupuncture for treatment of
      Alzheimer disease (AD). METHODS: SD rats were randomly divided into a normal
      group, a sham operation group, a model group and an electroacupuncture group, 12
      rats in each group. The AD rat model was prepared by microinjection of amyloid
      beta protein (Abeta1-40) into the Meynert nucleus. In the electroacupuncture
      group, electroacupuncture was given at "Baihui" (GV 20), "Taixi" (KI 3),
      "Zusanli" (ST 36). The learning and memory ability was assessed by Morris water
      maze and the glial cell activity in the hippocampus was determined by
      immunohistochemistry. RESULTS: Compared with the normal group, the glial cell in
      the hippocampus was activated with increase of the number, and the learning and
      memory ability reduced in the model group (P < 0.01). After treatment, as
      compared with the model group, the number of the activated glial cells was
      reduced and the learning and memory ability was improved in the
      electroacupuncture group (P < 0.01). CONCLUSION: Electroacupuncture treatment can
      decrease the number of activated glial cells so as to protect the neurons,
      improving the learning and memory ability in the AD rat.

PMID- 19391540
TI  - [Study on electroacupuncture treatment of depression by magnetic resonance
      imaging].
AB  - OBJECTIVE: To explore the changes of metabolites in brain after treatment by
      analysis on 1H-MRS examination of the hippocampus and prefrontal lobe in the
      healthy volunteers and the depression patients. METHODS: Seventy-five cases of
      mild and moderate depression were randomly divided into groups A, B and C, 25
      cases in each group. The group A was treated with oral administration of Prozac
      capsule, 20 mg/d; the group B by electroacupuncture for 30-40 min and the needle
      was retained for 1 h, once each day, with main points Baihui (GV 20), Yin-tang
      (GV 29) and adjuvant acupoints selected; the group C by combination of the
      treatment methods in the groups A and B. They were treated for 6 weeks. Use PROBE
      J sequence at the MRI system on Single Voxel of ROI of each lateral of
      hippocampus and frontal lobe in the depression patients of the 3 groups. Compare
      the differences of N-acetylasp artate/creatine (NAA/Cr) and choline/creatine
      (Cho/Cr) between the healthy volunteers and the patients before and after
      treatment. RESULTS: Before treatment, NAA/Cr in the bilateral hippocampus
      decreased in the 3 groups as compared with the control group, and after
      treatment, NAA/Cr in the bilateral hippocampus of the group B and in the right
      hippocampus of the group C increased compared with that before treatment (P <
      0.05), and NAA/Cr in the left hippocampus of the group C significantly increased
      as compared with that before treatment (P < 0.01). Before treatment, Cho/Cr in
      the bilateral prefrontal lobe in the 3 groups increased as compared with that in
      the control group (P < 0.05), after treatment, Cho/Cr in the bilateral prefrontal
      lobes of the groups A, B and C significantly decreased as compared with that
      before treatment (P < 0.05, P < 0.01). CONCLUSION: There are differences in
      contents of metabolites in corresponding parts in bilateral frontal lobes and
      hippocampus between the depression patient and healthy person.

PMID- 19391541
TI  - [Professor He Pu-ren: the founder of Santong method of acupuncture and
      moxibustion].
AB  - Professor He Pu-ren, the founder of Santong method of acupuncture and
      moxibustion, is a well known acupuncturist at home and abroad. His main
      contributions include combined martial arts and Chinese medicine, showing obvious
      therapeutic effect; taking part in establishment of The Department of
      Acupuncture, Beijing Chinese Medicine Hospital; creating Santong method of
      acupuncture and moxibustion; advocating fire needle therapy; writing medical
      books and teaching students; advocating the culture of acupuncture; making the
      metal model of acupuncture and moxibustion, and others. His achievements have
      become an important part of acupuncture and moxibustion science.

PMID- 19391542
TI  - [Approach to some problems in the national standard Standardized Manipulation of
      Acupuncture and Moxibustion, Part IV, Three-Edged Needle].
AB  - Main difficulties and problems in working out the national standard Manipulation
      Standardization of Acupuncture and Moribustion Techniques for Three-edged Needle
      are discussed. The difficult points include selection of technical terms;
      standardization and characteristics of Chinese medicine; quantification of
      bleeding amount in three-edged needle therapy; basis and science of the standards
      stipulated. The problems that need further be studied and perfected for
      Manipulation Standardization of Acupuncture and Moxibustion Techniques for Three
      edged Needle are put forward in the present paper.

PMID- 19391543
TI  - [Analysis on acupuncture and moxibustion literature in Medline database from 2000
      to 2007].
AB  - To summarize and analyze literature about acupuncture and moxibustion embodied in
      Medline Database from 2000 to 2007, the articles in Medline PubMed Database were
      retrieved by different retrieval tactics on line, in combination with artificial
      statistical analysis on the literature data. Results indicate that among a total
      of 4 041 articles about acupuncture and moxibustion retrieved from Medline in the
      8 years, 628 were published in Chinese and 3071 in English. These articles were
      involved in 836 journals, including 31 Chinese Journals. Eight hundred and forty
      one articles were from China mainland, Beijing (176), Shanghai (136) and Tianjin
      (43) were the top 3 provinces and cities of literature numbers. It is showed that
      most acupuncture and moxibustion articles embodied in Medline are published in
      many foreign publications in English as main, but this situation has greatly
      changed after Zhongguo Zhenjiu and other journals were cited by Medline since
      2006.

PMID- 19391544
TI  - [Design and application of a new type minor smoke warming moxibustion cup].
AB  - OBJECTIVE: To design a new type minor smoke warming moxibustion cup for
      convenient use of both the physicians and the patients. METHODS: The double-deck
      minor smoke warming moxibustion cup is fixed on the part receiving moxibustion by
      vacuum adsorption; the filtration device on the upper can filtrate and adsorb the
      harmful substance in the moxa-smoke, and the device with a double-temperature
      control on the lower can sensitively regulate the moxibustion temperature.
      RESULTS: This new type minor smoke warming moxibustion cup has the advantages of
      minor smoke discharge, convenient fixation, sensitive regulation of temperature,
      saving moxibustion material, lasting action, safety, besides the advantages of
      traditional moxibustion. CONCLUSION: The new type minor smoke warming moxibustion
      cup can use for treatment and prevention of diseases, suitable to clinical
      treatment and family health care.

PMID- 19391546
TI  - Like a thief in the night.

PMID- 19391545
TI  - [Study and prospects for clinical diseases treated with scraping therapy].
AB  - In order to explore characteristics of clinical diseases treated by scraping
      therapy, summarize laws of clinical application of scraping therapy, and prospect
      for research direction of scraping therapy in future, collect 437 articles about
      scraping therapy between 1994-2007 and analyze and summarize the treated diseases
      and methods of scraping therapy. Results indicate that scraping therapy has been
      widely applied to commonly encountered diseases and frequently encountered
      diseases in departments of internal medicine, surgery, gynecology and pediatrics,
      etc. with more obvious therapeutic effects. Clinically, it can combine with
      acupuncture and moxibustion, cupping, massage, blood-letting puncture and other
      methods. In future, the studies on standardization of manipulation and standards
      for assessment of therapeutic effect, suitable diseases and the mechanisms of
      scraping therapy, and development of tools and media, etc. of scraping therapy
      should be strengthened.

PMID- 19391547
TI  - Pandemic preparation must focus on meeting public health needs.
AB  - With the nation's heightened attention to security and police and military
      effectiveness to handle disaster situations, perhaps including a potential
      pandemic flu outbreak, too little is being done to prepare the health system to
      cope with a sudden spike in need, according to the American Civil Liberties
      Union.

PMID- 19391548
TI  - Recognition for home care's role in disaster preparedness: our time has
      come...but are we ready for it?
AB  - Those of us in the home care and hospice industry know we have a major role in
      disaster preparedness. Our history is rich with examples of that. We have
      participated in events such as the Great Influenza Pandemic of 1918 and other
      pandemics, mass immunizations programs, communicable disease outbreaks, and of
      course, after natural disasters such as Hurricane Katrina.

PMID- 19391549
TI  - Emergency preparedness: the continuing role of home care and hospice in New
      Jersey.

PMID- 19391551
TI  - Recovery puts VNA of Texas on the right path for disaster preparedness.

PMID- 19391550
TI  - Swarms, storms, and waves: oh my! The latest on avian flu.

PMID- 19391553
TI  - Cutting through the red tape: update of NAHC's efforts to ease regulatory
      constraints during emergencies.
AB  - The terrorist attacks on New York City and Washington, DC, on September 11, 2001,
      the hurricanes that struck the Gulf States in 2005, along with preparations for
      an impending influenza pandemic have dramatically underscored the vital role of
      all aspects of the health care delivery system, including home care, in
      addressing emergency situations.

PMID- 19391552
TI  - LivHOME's emergency planning pays off during California wildfires.
AB  - Last October, a series of disastrous wildfires struck our southern California
      region. Over a five-day period, at least 1500 homes were destroyed, and more than
      500,000 acres of land burned from Santa Barbara County to the United States
      Mexican border. More than 265,000 people were evacuated throughout California,
      nine people died, and 85 others were injured.

PMID- 19391554
TI  - Home care's critical role.

PMID- 19391556
TI  - Honoring fathers.

PMID- 19391555
TI  - Applausable caring at 35,000 feet.

PMID- 19391557
TI  - Better safe than sorry: using your Web site to promote disaster preparedness.

PMID- 19391558
TI  - Private equity investment in home health care: is the window of opportunity
      beginning to close?

PMID- 19391559
TI  - MedPAC examining Medicare hospice benefit reimbursement system.

PMID- 19391560
TI  - Home care to the rescue.

PMID- 19391561
TI  - Early legislative wins for Obama.

PMID- 19391562
TI  - Securing revenue with improved labor use.

PMID- 19391563
TI  - The importance of companion IT strategies.
AB  - Discussions of IT strategy should include not only which IT applications a
      healthcare organization should invest in, but also what strategies could maximize
      the organization's IT asset as a whole and what non-IT strategies could
      complement and help leverage the IT investment.

PMID- 19391564
TI  - Healthcare reform a near-term reality?
AB  - Cost savings might be realized by key health care reforms based on four
      interdependent areas of focus: 1) Health IT, 2) Comparative effectiveness, 3)
      Coordination of care, and 4) Consumerism.

PMID- 19391565
TI  - Karen Davis-- hope for healthcare reform.

PMID- 19391566
TI  - Benchmarking tools for reducing costs of care.
AB  - Publicly available data provide an excellent resource for benchmarking a
      hospital's performance around diagnostic groups. The benchmarking analysis should
      seek to identify any unexpected differences in a hospital's average costs
      relative to those of similar hospitals. A good starting place for such analysis
      is the most frequent diagnostic groups for Medicare, as defined by Medicare
      severity-based diagnosis-related groups. A finding of higher-than-expected costs
      relative to those of peers can provide an impetus for further investigation.

PMID- 19391567
TI  - Sustaining savings.
AB  - Organizations can sustain savings through spend visibility, demand management,
      and appropriate contracting and sourcing techniques. Going green--for example, by
      using multi-use versus single-use products--can produce long-term savings. A well
      defined materials management team, organized around spend categories, can help
      ensure that projected savings are fully realized.

PMID- 19391568
TI  - Financial implications of moving to a physician employment model.
AB  - Hospital employment of physicians can lead to better quality, coordination of
      care, and increased efficiency. The employment model is likely to be better
      suited for healthcare reforms that require a great degree of physician-hospital
      integration. A sophisticated analysis of the employment model must take into
      consideration physician-related costs and payments, access, competitive
      positioning, and alignment of incentives. Analysis of the physician employment
      should be performed in the context of all the strategic options available to a
      hospital.

PMID- 19391569
TI  - Give nurses the right tools ... and labor costs go down.
AB  - Keys to reducing premium labor costs: Create a centralized staffing office.
      Develop a predictive model, such as one using census points, to forecast demand.
      Train staff on the new processes. Monitor performance monthly. Define key
      staffing processes for core and seasonal staffing needs.

PMID- 19391570
TI  - Improving patient flow in the cath lab.
AB  - Key steps that led to Kennestone Hospital's success in improving patient flow in
      the cath lab included: Developing an urgency classification system for patients.
      Creating a more accurate scheduling system to increase throughput and efficiency.
      Establishing a project team. Developing a time line. Recognizing ongoing
      challenges

PMID- 19391571
TI  - Improving healthcare recruitment: the jupiter medical center experience.
AB  - Hospitals that want to improve their recruitment efforts should: Make recruitment
      a priority within the organization. Take steps to reduce high vacancy rates and
      turnover among first-year employees. Develop a recruitment marketing plan for key
      positions. Establish human resources metrics to track costs and effectiveness of
      recruiting efforts. Enhance the recruitment process for hiring managers and job
      candidates.

PMID- 19391572
TI  - Measuring ROI of medical banking on the healthcare revenue cycle.

PMID- 19391573
TI  - Mechanism of membrane permeabilization by a bacterial trehalose lipid
      biosurfactant produced by Rhodococcus sp.
AB  - The interactions of a succinoyl bacterial trehalose lipid biosurfactant produced
      by Rhodococcus sp. with phospholipid vesicles, leading to membrane
      permeabilization, are studied by means of calorimetric and fluorescence and
      absorption spectroscopical techniques in search for a molecular model. The
      critical micelle concentration (CMC) of trehalose lipid is determined, by surface
      tension measurements, to be 300 muM. Binding of trehalose lipid to
      palmitoyloleoylphosphatidylcholine membranes is studied by means of isothermal
      titration calorimetry. The partition constant, in conjunction with the CMC,
      indicates that trehalose lipid behaves as a weak detergent, which prefers
      membrane incorporation over micellization. Addition of trehalose lipid to
      palmitoyloleoylphosphatidylcholine large unilamellar vesicles results in a size
      selective leakage of entrapped solutes to the external medium. Experimental
      evidence is provided to support the requirement of a stage of flip-flop prior to
      membrane permeabilization, and the rate of flip-flop is measured using
      fluorescent probes assays. The lipid composition of the target membrane is found
      to modulate the leakage process to a great extent. It is proposed that trehalose
      lipid incorporates into phosphatidylcholine membranes and segregates within
      lateral domains which may constitute membrane defects or "pores", through which
      the leakage of small solutes might take place. The results presented here
      contribute to the knowledge of the molecular mechanisms underlying the membrane
      related biological actions of this bacterial trehalose lipid biosurfactant.

PMID- 19391574
TI  - Mesoporous silica sphere-polysulfone mixed matrix membranes for gas separation.
AB  - A series of mixed matrix membranes were prepared comprising polysulfone Udel
      matrix and ordered mesoporous silica spheres as filler with loadings varying
      between 0 and 32 wt %. The interaction between the filler and the polymer was
      studied by scanning and transmission electron microscopy, thermogravimetry,
      differential scanning calorimetry and dynamic mechanical analyses, N2 porosity, X
      ray photoelectron spectrometry, and attenuated total reflectance Fourier
      transform infrared spectroscopy. All these characterizations allowed us to infer
      an optimum interaction based on both the penetration of the polymer chains into
      the mesoporosity of the silica spheres and the establishment of hydrogen bondings
      between the hydroxyl-rich surface and the aryl ether groups of the polymer. An
      optimum loading of 8 wt % was found in terms of H2/CH4 separation performance. In
      addition, the optimum membrane was tested for CO2/N2 separation.

PMID- 19391575
TI  - Two asymmetric syntheses of AMG 221, an inhibitor of 11beta-hydroxysteroid
      dehydrogenase type 1.
AB  - Two asymmetric syntheses of AMG 221 (2), an inhibitor of 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) discovered in our laboratories, are reported.
      One of the syntheses utilizes chiral trimethylsilyl cyanohydrin 12 as starting
      material and the other utilizes its enantiomer ent-12. The displacement approach
      involves the conversion of 12 to 2 via a six-step sequence, occurs with net
      inversion of configuration, and employs amine 6 as starting material. This route
      features a novel approach toward chiral dialkylsubstituted alpha-mercaptoacids.
      The cyclization approach entails the synthesis of 2 from ent-12 in 2 steps, takes
      place with net retention of configuration, and uses thiourea 8 as starting
      material. The final step of this route exemplifies a novel synthesis of chiral C
      5 dialkylsubstituted 2-aminothiazolones from chiral alpha-hydroxyacids and
      thioureas. Insights into the mechanism of this transformation and study of the
      effect of the medium on the stereochemical outcome of the reaction are presented.

PMID- 19391576
TI  - Preparation of porous anodic alumina with periodically perforated pores.
AB  - Anodization of aluminum is an excellent nonlithographic alternative to
      conventional fabrication approaches for low-cost and large-scale synthesis of a
      variety of nanostructured materials. In this work, the preparation of anodic
      alumina oxide (AAO) with unique three-dimensional (3D) porous structures that
      consist of periodically perforated nanopores is reported. The fabrication method
      combines electrochemical anodization of aluminum and chemical etching. The key
      feature of this process is cyclic anodization where an oscillatory current signal
      was applied to create AAO with periodically shaped pore structures. Spatially
      specific dissolution of the pore walls was directed by modulated pore structures
      during chemical etching to generate hexagonally ordered arrays of holes with
      periodic distribution across the pore length.

PMID- 19391577
TI  - Microscale patterning of hydrophobic/hydrophilic surfaces by spatially controlled
      galvanic displacement reactions.
AB  - In this letter, we report the design and fabrication of different metal patterns
      for the realization of spatially controlled hydrophobic/hydrophilic regions with
      micrometer resolution. The fabrication procedure, based on a combination of
      lithographic techniques and wet-chemistry reactions (namely, spontaneous Galvanic
      displacement reactions) is reliable, undemanding, and highly versatile, allowing
      the achievement of precise spatial control along with the use of a wide variety
      of different materials.

PMID- 19391578
TI  - Fluorophobic effect for building up the surface morphology of electrodeposited
      substituted conductive polymers.
AB  - During the past decade, several works display the electrochemical polymerization
      of fluorinated monomers as a highly efficient method (one-pot method, mild
      conditions, various morphologies) to obtain superhydrophobic or superoleophobic
      surfaces. Here, we point out the fluorinated tails not only are useful to
      increase both hydrophobicity and oleophobicity but also are involved in the
      formation of surface structurations: two necessary conditions for liquid
      dewetting. To support this assertion, a series of fluorinated pyrrole derivatives
      and their hydrocarbon homologues were synthesized and electrochemically deposited
      in the same conditions. Whereas hydrocarbon pyrroles give rise to smooth films,
      structured films are achieved from fluorinated pyrroles. The abundance of the
      surface structurations depends on the length of the fluorinated tail.

PMID- 19391579
TI  - Stochastic kinetic analysis of the Frank model. Stochastic approach to flow
      through reactors.
AB  - The continuous time discrete state stochastic kinetic approach and its extension
      to flow-through reactors was used to study a straightforward modification of the
      Frank model to interpret absolute asymmetric synthesis, which is impossible using
      deterministic approaches. Computational methods for calculating multidimensional
      probability distributions and expectations for enantiomeric excess were
      developed. The results showed that narrow focus on the conventionally defined
      enantiomeric excess could lead to misleading conclusions and the yield-adjusted
      enantiomeric excess is often more useful. Closed systems proved to be more
      favorable for the formation of high enantiomeric excesses than flow-through
      reactors and the importance of mutual antagonism can also be questioned in the
      original Frank model. It was also shown that a flow-through reactor with a
      relatively small number of molecules predicts the behavior of much larger systems
      well.

PMID- 19391580
TI  - Biphenylene-substituted ruthenocenylphosphine for Suzuki-Miyaura coupling of
      sterically hindered aryl bromides.
AB  - A highly general, active, and stable catalytic system was realized in the
      palladium-catalyzed Suzuki-Miyaura reactions of sterically hindered aryl bromides
      with arylboronic acids using biphenylene-substituted di-tert
      butylruthenocenylphosphine (R-Phos) as a supporting ligand.

PMID- 19391581
TI  - Polynomial-time-scaling quantum dynamics with time-dependent quantum Monte Carlo.
AB  - Here we study the dynamics of many-body quantum systems using the time-dependent
      quantum Monte Carlo method where the evolution is described by ensembles of
      particles and guide waves. The exponential time scaling inherent to the quantum
      many-body problem is reduced to polynomial-time computation by solving
      concurrently a set of coupled Schrodinger equations for the guide waves in
      physical space and a set of first-order equations for the Monte Carlo walkers. We
      use effective potentials to account for the local and nonlocal quantum
      correlations in time-varying fields, where for fermionic states an exchange
      "hole" is introduced explicitly through screened Coulomb potentials. The walker
      distributions for the ground states of para- and ortho-helium reproduce well the
      statistical properties, such as the electron-pair density function, of the real
      atoms. Our predictions for the dipole response and the ionization of an atom
      exposed to strong ultrashort optical pulse are in good agreement with the exact
      results.

PMID- 19391583
TI  - Surface functionalization of titanium with carboxymethyl chitosan and immobilized
      bone morphogenetic protein-2 for enhanced osseointegration.
AB  - Orthopedic implant failure has been attributed mainly to loosening of the implant
      from host bone, which may be due to poor bonding of the implant material to bone
      tissue, as well as to bacterial infection. One promising strategy to enhance
      tissue integration is to develop a selective biointeractive surface that
      simultaneously enhances bone cell function while decreasing bacterial adhesion.
      In this in vitro study, the surfaces of titanium alloy substrates were
      functionalized by first covalently grafting carboxymethyl chitosan (CMCS),
      followed by the conjugation of bone morphogenetic protein-2 (BMP-2) to the CMCS
      grafted surface. Bacterial adhesion on the substrates was assayed with
      Staphylococcus aureus and Staphylococcus epidermidis . Cell functions were
      investigated using osteoblasts and human bone marrow-derived mesenchymal stem
      cells. The results showed that bacterial adhesion on both the CMCS and CMCS-BMP-2
      functionalized surfaces was significantly reduced compared to that on the
      pristine substrates. In addition, the CMCS-BMP-2 modified substrates
      significantly promoted attachment, alkaline phosphatase activity, and calcium
      mineral deposition of both osteoblast and human bone marrow-derived mesenchymal
      stem cells. The achievement of the dual functions of bacterial adhesion reduction
      and cell function promotion by the CMCS-BMP-2 modified titanium substrates
      illustrates the good potential of such surfaces for enhancement of tissue
      integration and implant longevity.

PMID- 19391582
TI  - Enzymes and inhibitors in neonicotinoid insecticide metabolism.
AB  - Neonicotinoid insecticide metabolism involves considerable substrate specificity
      and regioselectivity of the relevant CYP450, aldehyde oxidase, and phase II
      enzymes. Human CYP450 recombinant enzymes carry out the following conversions:
      CYP3A4, 2C19, and 2B6 for thiamethoxam (TMX) to clothianidin (CLO); 3A4, 2C19,
      and 2A6 for CLO to desmethyl-CLO; 2C19 for TMX to desmethyl-TMX. Human liver
      aldehyde oxidase reduces the nitro substituent of CLO to nitroso much more
      rapidly than it does that of TMX. Imidacloprid (IMI), CLO, and several of their
      metabolites do not give detectable N-glucuronides but 5-hydroxy-IMI, 4,5-diol
      IMI, and 4-hydroxythiacloprid are converted to O-glucuronides in vitro with mouse
      liver microsomes and UDP-glucuronic acid or in vivo in mice. Mouse liver cytosol
      with S-adenosylmethionine converts desmethyl-CLO to CLO but not desmethyl-TMX to
      TMX. Two organophosphorus CYP450 inhibitors partially block IMI, thiacloprid, and
      CLO metabolism in vivo in mice, elevating brain and liver levels of the parent
      compounds while reducing amounts of the hydroxylated metabolites.

PMID- 19391584
TI  - Assessment of antibacterial properties of polyvinylamine (PVAm) with different
      charge densities and hydrophobic modifications.
AB  - Hydrophobically modified and unmodified polyvinylamines (PVAm), including a total
      of five polymers, were tested against both gram-negative ( Escherichia coli ) and
      gram-positive ( Bacillus subtilis ) bacteria for antimicrobial activity. The
      assessment of PVAm in solution against bacteria is described, and the influence
      of the charge density and of the hydrophobic modification of the polyelectrolyte
      is discussed. The antimicrobial activity was found to depend upon the
      concentration of PVAm and also on the type of bacteria used. The results also
      indicated that no direct relationship exists between antimicrobial activity and
      charge density of the different PVAms. It was, however, observed that an alkyl
      chain length of six or eight alkane units had a substantial effect on the
      bacteria investigated. The best combined antibacterial activity for the two
      bacteria tested was achieved for PVAm with a C(6) alkane substituent (PVAm C(6)).
      To evaluate the antimicrobial activity on a solid substrate, PVAm C(6) was
      further studied after being deposited onto a glass slide and the results show a
      large reduction in bacterial infection.

PMID- 19391586
TI  - Messenger-tagging electrosprayed ions: vibrational spectroscopy of suberate
      dianions.
AB  - The gas-phase vibrational spectroscopy of bare and monohydrated suberate
      dianions, (-)OOC-(CH(2))(6)-COO(-) and (-)OOC-(CH(2))(6)-COO(-).H(2)O, is studied
      by infrared photodissociation aided by electronic structure calculations. To this
      end, the corresponding ion-Kr atom complexes are formed in a cooled buffer-gas
      filled ion trap, and their infrared vibrational predissociation spectra are
      measured in the range from 660 to 3600 cm(-1). The water molecule binds to one of
      the two carboxylate groups in a bidentate fashion, characterized by the splitting
      of the carboxylate stretching bands, a substantially blue-shifted water bending
      band, and the presence of anomalously broadened bands in the O-H stretching and
      H(2)O rocking region. The C-C backbone structure remains unperturbed by the
      addition of a water molecule or a Kr atom. At 63 K, the all-trans isomer is the
      most abundant species, but evidence for dynamically interconverting conformers is
      also present from contributions to the absorption cross section on the low-energy
      tail of the C-H stretching region.

PMID- 19391585
TI  - Fast dynamics of semiflexible chain networks of self-assembled peptides.
AB  - We present the first neutron spin echo (NSE) measurements of self-assembling
      peptide hydrogel networks to study the fibril dynamics on the nanometer and
      nanosecond length and time scales. MAX1 and MAX8 are synthetic beta-hairpin
      peptides that undergo triggered self-assembly at the nanoscale to form a
      physically cross-linked network of fibrils with a defined cross-section. When
      subjected to physiological pH and ionic strength (pH 7.4, 150 mM NaCl), the
      soluble peptides fold into a beta-hairpin and, subsequently, self-assemble to
      form a structurally rigid hydrogel stabilized by noncovalent cross-links. The
      sequence of MAX8 is identical to MAX1 with the exception of one single amino acid
      substitution that reduces the net charge on the peptide. As a result, faster
      folding and self-assembly kinetics are observed for MAX8 at the same peptide
      concentration and identical buffer conditions, and gels with a larger storage
      modulus are formed. NSE measurements of the peptide hydrogels demonstrate that
      the self-assembled peptide fibrils can be described as semiflexible chains on
      nanolength and time scales. Alteration of the peptide sequence affected the
      nanoscale dynamics of the hydrogels but not to an extent comparable to the large
      difference observed in the bulk viscoelasticity. Small angle neutron scattering
      (SANS) of the hydrogels reveals increased scattering for MAX8 at low wavevectors,
      an indication of a heterogeneous network with a tighter mesh size. Therefore, we
      conjecture that the difference in elastic modulus arises from differences in
      assembly kinetics that result in increased fibrillar branching and physical cross
      links rather than a change in the fibril nanostructure or persistence length.

PMID- 19391587
TI  - On the urea action mechanism: a comparative study on the self-assembly of two
      sugar-based surfactants.
AB  - Studies on the effect of urea on micelle formation and structure of n-octyl-beta
      D-thioglucoside (OTG) and N-decanoyl-N-methylglucamide (MEGA-10) were carried out
      by using the steady-state and time-resolved fluorescence techniques, together
      with combined static and dynamic light scattering measurements. A similar
      increase in the critical micelle concentration with the urea addition was
      observed for both surfactants. This behavior was attributed to a rise in the
      solubility of hydrocarbon tails and the increase of solvation of the headgroup of
      the surfactants in the presence of urea. Structural studies mainly based on the
      analysis of the hydrodynamic radius and aggregation number of micelles revealed
      that urea induces changes much more significant on micelles of OTG. Particularly,
      it was found that, whereas the surface area per headgroup of OTG increases with
      the urea concentration, it does decrease in the case of MEGA-10. This fact
      suggests that different action mechanisms operate for both surfactants.
      Accordingly, investigations on the micellar microstructure based on the study of
      microenvironmental properties such as micropolarity and microviscosity also
      indicated a more pronounced effect in the case of OTG. Although changes were not
      observed in the hydrophobic inner region of both micellar systems, a significant
      increase of polarity and viscosity in the micellar interface of OTG suggests a
      direct participation of urea in the micellar solvation layer. The differences
      between the observed behaviors for both micellar systems were interpreted on the
      basis of two features: the weaker hydration and greater rigidity of the OTG
      headgroup as compared with MEGA-10.

PMID- 19391588
TI  - Synthesis of carbocyclic aromatic compounds using ruthenium-catalyzed ring
      closing enyne metathesis.
AB  - General synthetic methods of substituted carbocyclic aromatic compounds are
      reported. Ring-closing enyne metathesis (RCEM)/dehydration of 1,5-octadien-7-yn-4
      ols 6 and RCEM/tautomerization of 1,5-octadien-7-yn-4-ones 7 furnished a wide
      variety of substituted styrenes 4 and 4-vinylphenols 8, respectively. Acyclic
      precursors 6 and 7 were readily prepared from beta-halo-alpha,beta-unsaturated
      aldehydes 9 or 3-halo-2-propene-1-ols 13 by utilizing combinations of the
      Sonogashira coupling, allylation, and the Dess-Martin oxidation. The
      RCEM/dehydration for the synthesis of 1,3,5-tris(1-phenylethenyl)benzene
      derivative 4r and the RCEM/RCM/dehydration for the synthesis of 1,1'-binaphthyl
      derivative 19a are also presented as applications of this method.

PMID- 19391589
TI  - Investigating hydroxide anion interfacial activity by classical and multistate
      empirical valence bond molecular dynamics simulations.
AB  - Molecular dynamics simulations were carried out to understand the propensity of
      the hydroxide anion for the air-water interface. Two classes of molecular models
      were used, a classical polarizable model and a polarizable multistate empirical
      valence bond (MS-EVB) potential. The latter model was parametrized to reproduce
      the structures of small hydroxide-water clusters based on proton reaction
      coordinates. Furthermore, nuclear quantum effects were introduced into the MS-EVB
      model implicitly by refitting its potential energy function to account for them.
      The final MS-EVB model showed reasonable agreement with experiment and ab initio
      molecular dynamics simulations for dynamical and structural properties. The free
      energy profiles for both the classical and MS-EVB models were mapped out across
      the air-water interface, and the classical model gave a higher free energy at the
      interface with respect to bulk. However, the MS-EVB model gave little free-energy
      difference between when the hydroxide anion was in the bulk and when it was
      present at the air-water interface with its oxygen fully solvated and its
      hydrogen pointing toward the vapor. When the hydroxide oxygen started to
      desolvate, the free energy increased dramatically, suggesting that the hydroxide
      anion can be found in the interfacial region.

PMID- 19391590
TI  - Valence-bond/coherent-states approach to the charge equilibration model I.
      Valence-bond models for diatomic molecules.
AB  - A valence-bond (VB)/coherent-states (CS) approach to the charge equilibration
      (CE) model for diatomic molecules is presented in this work (VB part) and its
      sequel (CS part). By emphasizing theoretical aspects, this approach obtains the
      classical-electrostatics CE model from a quantum VB model in conjunction with the
      CS theory. For the VB part, a VB generalized CE (VB/GCE) model, which contains
      the CE model as a subcase, is derived from a two-electron, three-state VB model
      via the sequential application of seven approximations. Unlike its CE subcase,
      the VB/GCE model provides a satisfactory charge-transfer description at
      dissociation as illustrated with HF((g)) and other molecules. Through the
      previous derivation, CE charges and CE Coulomb interactions are elucidated in
      terms of VB Mulliken charges and VB atomic interactions, respectively.
      Modifications in the above derivation can generate a family of related VB/GCE
      models that includes the aforesaid VB/GCE model. Despite their classical
      appearance, all of the VB/GCE and CE models involve VB wave functions
      corresponding to ground and first-excited states. Moreover, all of the VB/GCE and
      CE energy and charge optimizations are proven to be equivalent to the variational
      eigenvector equation procedures of the underlying VB models. The quantum
      mechanics/classical-electrostatics connection implicit in this work is further
      elaborated by means of VB CS sets in the sequel. The VB/CS treatment of
      polyatomic molecules and additional tests of the present approach will be
      reported in later papers in this series.

PMID- 19391591
TI  - Effect of nitrogen supplementation and Saccharomyces species on hydrogen sulfide
      and other volatile sulfur compounds in shiraz fermentation and wine.
AB  - A Shiraz must with low yeast assimilable nitrogen (YAN) was supplemented with two
      increasing concentrations of diammonium phosphate (DAP) and fermented with one
      Saccharomyces cerevisiae and one Saccharomyces bayanus strain, with maceration on
      grape skins. Hydrogen sulfide (H(2)S) was monitored throughout fermentation, and
      a total of 16 volatile sulfur compounds (VSCs) were quantified in the finished
      wines. For the S. cerevisiae yeast strain, addition of DAP to a final YAN of 250
      or 400 mg/L resulted in an increased formation of H(2)S compared to
      nonsupplemented fermentations (100 mg/L YAN). For this yeast, DAP-supplemented
      fermentations also showed prolonged formation of H(2)S into the later stage of
      fermentation, which was associated with increased H(2)S in the final wines. The
      S. bayanus strain showed a different H(2)S production profile, in which
      production was inversely correlated to initial YAN. No correlation was found
      between total H(2)S produced by either yeast during fermentation and H(2)S
      concentration in the final wines. For both yeasts, DAP supplementation yielded
      higher concentrations of organic VSCs in the finished wines, including sulfides,
      disulfides, mercaptans, and mercaptoesters. PCA analysis indicated that nitrogen
      supplementation before fermentation determined a much clearer distinction between
      the VSC profiles of the two yeasts compared to nonsupplemented fermentations.
      These results raise questions concerning the widespread use of DAP in the
      management of low YAN fermentations with respect to the formation of reductive
      characters in wine.

PMID- 19391592
TI  - Self-assembly of esters of arjunolic acid into fibrous networks and the
      properties of their organogels.
AB  - Nine esters of a naturally occurring triterpenoid, arjunolic acid (from
      Terminalia arjuna), with alkyl chains have been synthesized, and their self
      assembly has been studied in organic liquids. All of the esters examined were
      found to be excellent gelators. No birefringence was detected in optical
      micrographs of the transparent toluene gels with 5% (w/w) ethyl arjunolate or 5%
      (w/w) p-nitrobenzyl arjunolate as the gelator, but a spherulitic-type pattern was
      seen for a gel of 1.2% (w/w) p-nitrobenzyl arjunolate in 1/1 (w/w)
      chloroform/cyclohexane. Electron microscope images revealed self-assembled
      fibrillar network (SAFIN) structures with right-handed helical ribbons in some
      gels. With increasing concentration of the gelators, the gel-to-sol transition
      temperature (T(gel)) increased and then approached plateau values. Differential
      scanning thermograms demonstrated that the heats for transition from transparent
      gels to sols of ethyl arjunolate or p-nitrobenzyl ajunolate in toluene are very
      small. Powder X-ray diffractograms revealed that the molecular packing in the
      SAFIN of the 5% (w/w) ethyl aijunoate in the toluene gel was amorphous and
      similar to the diffractogram recorded for the neat gelator. Although the
      diffractogram of neat p-nitrobenzyl arjunolate consisted of broad peaks,
      suggesting disordered packing, the low-angle peaks of the corresponding toluene
      gel were much sharper; these results indicate more crystalline packing in the
      SAFIN than in the neat gelator. The kinetics and growth of the transformation of
      sols of p-nitrobenzyl arjunolate in 1/1 (w/w) chloroform/cyclohexane to their
      gels have been investigated at different incubation temperatures by circular
      dichroism spectroscopy. The data have been analyzed to probe the mechanism of
      SAFIN formation and the relationship between the molecular structures of the
      esters of arjunolic acid and their abilities to function as gelators of a wide
      variety of organic liquids.

PMID- 19391593
TI  - Process research and development for a tetrazole-based growth hormone
      secretagogue (GHS) pharmaceutical development candidate.
AB  - BMS-317180 (1) is a potent, orally active agonist of the human growth hormone
      secretagogue (GHS) receptor. This manuscript details the process research and
      development efforts that enabled the synthesis of the phosphate salt of 1 on a
      multi-kilogram scale. Key considerations in the development of this process
      focused on safe execution and the requirement for telescoped synthetic
      transformations (i.e., without isolation of intermediate products) to contend
      with a lack of suitably crystalline products.

PMID- 19391594
TI  - A chemical genetic method for generating bivalent inhibitors of protein kinases.
AB  - We report a new chemical genetic method for creating bivalent ligands of protein
      kinases. The kinase inhibitors that are generated with this methodology consist
      of two components: (1) a synthetic, small molecule that targets the ATP-binding
      cleft and (2) a peptidic ligand that enhances selectivity between kinases by
      targeting a secondary binding domain. A key feature of these bivalent inhibitors
      is that they are assembled on a protein scaffold with a chemoselective protein
      labeling technique. The utility of this methodology is demonstrated through the
      generation of a panel of protein-small molecule conjugates that simultaneously
      target the SH1 and SH3 domains of the closely related tyrosine kinases Src and
      Abl. The assembled bivalent ligands are significantly more potent inhibitors of
      Src and Abl than either modular component alone. Importantly, these protein-small
      molecule conjugates show a high degree of selectivity for their intended kinase
      target.

PMID- 19391595
TI  - Octahedral HSiCl3 and HSiCl2Me adducts with pyridines.
AB  - Stable solid adducts of substituted pyridines (Rpy) with HSiCl(3) and HSiCl(2)Me
      were prepared in high yields under aprotic and anaerobic conditions at room
      temperature. The octahedral complexes of HSiCl(3) underwent dismutation reactions
      in polar solvents. In contrast, the HSiCl(2)Me(Rpy)(2) adducts were not
      susceptible to dismutation under comparable conditions, but they tended to
      dissociate more easily because of the reduced Lewis acidity of HSiCl(2)Me
      relative to HSiCl(3). The bonding between silicon and its surrounding ligands is
      highly ionic, as can be seen from QTAIM and charge distribution analyses. (29)Si
      CP/MAS spectra in combination with quantum-chemical calculations show that the
      lowest shielding is along the Cl-Si-Cl axis. The other two components of the
      shielding tensor are oriented along the N-Si-N and H-Si-Cl/Me axes. It is known
      that many reactions of (hydrido)chlorosilanes are catalyzed by pyridine bases.
      Therefore, the results presented here provide a basis for better control of these
      reactions, especially chlorine substitution and hydrosilylation.

PMID- 19391596
TI  - Synthesis of a carboxylate functionalized bis-amino acid monomer.
AB  - The synthesis of the first functionalized bis-amino acid monomer proAc(2S3S4R) 1
      that carries an acetyl side chain is presented. This monomer was incorporated
      into oligomer 3 and the solution phase structure was determined by using two
      dimensional nuclear magnetic resonance. The solution structure confirmed the
      intended connectivity and stereochemistry of the oligomer. This first
      functionalized bis-amino acid represents a milestone toward functionalized bis
      peptide nanostructures for catalytic, molecular recognition, and nanotechnology
      applications.

PMID- 19391597
TI  - Synthesis and characterization of new mono- and heptazinc complexes with unusual
      amide coordination modes.
AB  - Two novel, a mono- and a heptanuclear, zinc complexes have been prepared and
      characterized by exploiting the flexibility and chelating and bridging ability of
      a new carboxylate- and amide-rich dinucleating ligand under different reaction
      conditions.

PMID- 19391598
TI  - A minima hopping study of all-atom protein folding and structure prediction.
AB  - The minima hopping algorithm (MHOP) to find global minima on potential energy
      surfaces is used for protein structure prediction. The energy surface of the
      protein is represented with an all-atom OPLS force field and an implicit free
      energy solvation term. The system we studied here is the small 10-residue beta
      hairpin mini-protein, chignolin. Starting from a completely extended structure,
      we found minima with <0.5 A rms coordinate deviation from the geometry-optimized
      native experimental conformation. A few lowest-energy conformations were used for
      the calculation of NMR-restraint violations and chemical shifts, and the local
      minima found during each run leading to the global minimum were connected to
      trace out a search pathway of the folding process.

PMID- 19391599
TI  - Polymorphism in high-crystalline-stability metal-organic nanotubes.
AB  - By application of mixed organic ligands of 5-amino-2,4,6-triiodoisophthalic acid
      (H(2)ATIBDC) and 4,4'-bipyridine (bpy) to assemble with Zn ions at room
      temperature, two novel polymorphic structures, Zn(ATIBDC)(bpy).3H(2)O (denoted as
      MONT-1 and MONT-2), possessing one-dimensional metal-organic nanotubular
      structures have been synthesized and characterized. MONT-1 was generated by
      connection of the zero-dimensional Zn-bpy squares through the bridging ATIBDC
      ligands, while MONT-2 was formed by connection of the one-dimensional Zn-bpy
      helix through the ATIBDC ligands. Both nanotubes possess highly crystalline
      stabilities and can absorb the uncoordinated water molecules reversibly.

PMID- 19391600
TI  - Hybrid core-shell nanowire forests as self-selective chemical connectors.
AB  - Conventional connectors utilize mechanical, magnetic, or electrostatic
      interactions to enable highly specific and reversible binding of the components
      (i.e., mates) for a wide range of applications. As the connectors are
      miniaturized to small scales, a number of shortcomings, including low binding
      strength, high engagement/disengagement energies, difficulties with the
      engagement, fabrication challenges, and the lack of reliability are presented
      that limit their successful operation. Here, we report unisex, chemical
      connectors based on hybrid, inorganic/organic nanowire (NW) forests that utilize
      weak van der Waals bonding that is amplified by the high aspect ratio geometric
      configuration of the NWs to enable highly specific and versatile binding of the
      components. Uniquely, NW chemical connectors exhibit high macroscopic shear
      adhesion strength (approximately 163 N/cm(2)) with minimal binding to non-self
      similar surfaces, anisotropic adhesion behavior (shear to normal strength ratio
      approximately 25), reusability (approximately 27 attach/detach cycles), and
      efficient binding for both micro- and macroscale dimensions.

PMID- 19391601
TI  - Remote-excitation surface-enhanced Raman scattering using propagating Ag nanowire
      plasmons.
AB  - Using propagating plasmons on silver nanowires as an excitation source we perform
      surface-enhanced Raman scattering (SERS) at a nanoparticle/wire junction located
      remotely from the laser illumination spot with sensitivities in a few molecules
      range. Simultaneous multisite remote-excitation SERS sensing can also be
      achieved.

PMID- 19391602
TI  - De novo sequencing of RCB-1 to -3: peptide biomarkers from the castor bean plant
      Ricinus communis.
AB  - Ricinus communis (also know as the castor bean plant) whose forbears escaped from
      suburban gardens or commercial cultivation grow wild in many countries. In
      temperate and tropical climates seeds will develop to maturity, and plants may be
      perennial. In Australia these plants have become widespread and are regarded as
      noxious weeds in many localities. The seeds of R. communis contain ricin, a
      protein toxin which can easily be extracted into an aqueous solution. Ricin is
      toxic by ingestion, inhalation, and injection. The history of terrorist and
      anarchist interest in the use of seeds from R. communis has driven the
      development of strategies for determination of cultivar and geographic location
      of the source of an extract of wild-grown castor bean seed. This forensic
      information is of considerable interest to law enforcement and intelligence
      organizations. During forensic studies of both the metabolome and proteome of
      extracts from eight specimens of six different cultivars of R. communis
      ("zanzibariensis" collected from Kenya and Tanzania, "gibsonii", "impala",
      "dehradun", "carmencita", and "sanguineus" collected from Spain and Tanzania),
      three peptide biomarkers (designated Ricinus communis biomarkers, or RCB) were
      identified in both the MALDI and electrospray LC-MS spectra. Two of these
      peptides (RCB-1 and RCB-2) were present in varying amounts in all cultivars,
      while RCB-3 was present only in the "carmencita" cultivar. The amino acid
      sequences of RCB-1 to -3 were determined using LC-MS(n) fragmentation and de novo
      sequencing on both the intact and the carbamidomethyl modified peptides. The
      connectivity of the two disulfide bonds that were present in all three RCB were
      determined using a strategy of partial reduction and differential alkylation
      using tris-(2-carboxyethyl)phosphine with N-ethylmaleimide to reduce and alkylate
      the most accessible disulfide bond, followed by reduction and alkylation of the
      remaining disulfide bond with dithiolthreitol and iodoacetamide. The possible
      functional role of RCB-1 to -3 in R. communis seeds is also discussed.

PMID- 19391603
TI  - Second-harmonic whispering-gallery modes in ZnO nanotetrapod.
AB  - We present the observation of second-harmonic (SH) whispering-gallery modes
      (WGMs) in the hexagonal cross-sections of the tapered ZnO nanotetrapod legs.
      Because of the continuously changing diameter in the leg, several orders of the
      WGMs at different SH wavelengths can be on resonance simultaneously at different
      locations along the leg. The strongest SH WGMs occur when the polarization of the
      fundamental excitation beam is parallel to the c-axis of the crystal along the
      leg.

PMID- 19391604
TI  - Phase-change Ge-Sb nanowires: synthesis, memory switching, and phase-instability.
AB  - We report the synthesis and characterization of phase-change Ge-Sb nanowires with
      two different eutectic compositions and their memory switching characteristics.
      Under application of electric-fields with controlled pulse amplitude and duration
      times, Sb-rich (Sb > or = 86 at. %) eutectic Ge-Sb nanowires show phase-change
      based memory switching, while another eutectic GeSb (Ge:Sb = 1:1) nanowires do
      not show electronic memory switching at all. However, under repeated
      measurements, Sb-rich Ge-Sb nanowires display an increase of resistance of the
      low resistive state. The observed electrical irreversibility for Sb-rich Ge-Sb
      nanowires is attributed to the structural and compositional instability due to
      the phase-separation of Ge out of homogeneous Ge-Sb as observed from rapid
      thermal annealing and transmission electron microscopy experiments. Implications
      for design of Te-free nanoscale materials for phase change memory applications
      are also discussed.

PMID- 19391605
TI  - Simplexins A-I, eunicellin-based diterpenoids from the soft coral Klyxum simplex.
AB  - Nine new eunicellin-based diterpenoids, simplexins A-I (1-9), were isolated from
      a Dongsha Atoll soft coral, Klyxum simplex. The structures of these compounds
      were established by detailed spectroscopic analysis (IR, MS, 1D and 2D NMR) and
      by comparison with the physical and spectral data of related known compounds. The
      absolute configuration of 1 was determined by a modified Mosher's method.
      Compounds 1, 4, and 5 were found to be cytotoxic toward a limited panel of cancer
      cell lines. Compound 5 was shown to significantly inhibit the accumulation of the
      pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage
      cells.

PMID- 19391606
TI  - Synthesis of proline-based diketopiperazine scaffolds.
AB  - A number of natural products with interesting biological properties are based on
      a diketopiperazine scaffold. In this context, we have developed a diversity
      oriented and efficient synthetic strategy to highly functionalized proline-based
      diketopiperazines. In this paper we describe the stereoselective synthesis of
      various scaffolds resembling abundant natural product core structures. These
      scaffolds can be conjugated to a solid phase and are thus platforms for the
      construction of small compound libraries and the synthesis of natural products
      with diketopiperazine cores.

PMID- 19391607
TI  - Simple colloidal synthesis of single-crystal Sb-Se-S nanotubes with composition
      dependent band-gap energy in the near-infrared.
AB  - We report the first synthesis of high-quality binary and ternary Sb(2)Se(3-x)S(x)
      nanotubes across the entire compositional range from x = 0 to 3 via a simple, low
      cost, colloidal synthetic method of injection of Sb(III)-complex solution into a
      hot paraffin liquid containing Se, S, or a mixture thereof. In contrast to the
      classic rolling mechanism, the modular formation of the reported nanotubes
      follows a four-stage self-seeding process: (i) amorphous nanospheres, (ii) short
      crystalline nanotubes growing out of relatively large amorphous nanospheres,
      (iii) long crystalline nanotubes attached to small amorphous nanospheres, and
      (iv) single-crystal nanotubes. The obtained single-crystal nanotubes have tunable
      composition, orthorhombic phase, well-defined rectangular cross sections, and
      growth direction along [001], as revealed by X-ray diffraction, scanning electron
      microscopy, energy-dispersive X-ray spectroscopy, transmission electron
      microscopy, and selected area electron diffraction studies. UV-vis-NIR absorption
      spectroscopy reveals that the optical bandgap energy of the Sb(2)Se(3-x)S(x) (0 <
      or = x < or = 3) nanotubes increases quadratically with the sulfur concentration
      x with these bandgap energies falling in the range from 1.18 to 1.63 eV at the
      red edge of the solar spectrum. The present study opens a new avenue to low-cost,
      large-scale synthesis of high quality semiconductor nanotubes with technological
      applications in solar energy conversion and also for a wide range of optical
      nanodevices operating in the near-infrared.

PMID- 19391608
TI  - Probing intramolecular B-N interactions in ortho-aminomethyl arylboronic acids.
AB  - This work investigates the interplay between the intramolecular B-N dative
      bonding and solvent insertion in various ortho-methylamino arylboronic acids in
      protic media. (11)B NMR experiments were conducted to study the effect that the
      degree of substitution of the amine group has on B-N bonding versus solvent
      insertion. It was found that there is a slight increase in the amount of B-N
      dative bonding on going from a tertiary to a secondary to a primary amine group,
      but that solvent insertion dominates in all cases of the boronate esters. A X-ray
      crystal structure gives further insight into the structure of the solvent
      inserted boronate esters, showing that the inserted solvent has its hydrogen
      primarily on the amine. Lastly, studies of the use of boronate esters as
      receptors for simple alcohols and carboxylic acids are described.

PMID- 19391609
TI  - Restructuring of hex-Pt(100) under CO gas environments: formation of 2-D
      nanoclusters.
AB  - The atomic-scale restructuring of hex-Pt(100) induced by carbon monoxide with a
      wide pressure range was studied with a newly designed chamber-in-chamber high
      pressure STM and theoretical calculations. Both experimental and DFT calculation
      results show that CO molecules are bound to Pt nanoclusters through a tilted on
      top configuration with a separation of approximately 3.7-4.1 A. The phenomenon of
      restructuring of metal catalyst surfaces induced by adsorption and, in
      particular, the formation of small metallic clusters suggests the importance of
      studying structures of catalyst surfaces under high-pressure conditions for
      understanding catalytic mechanisms.

PMID- 19391610
TI  - Fast, sensitive hydrogen gas detection using single palladium nanowires that
      resist fracture.
AB  - Two types of pure palladium (Pd) nanowires, differentiated by microstructure,
      were electrodeposited: (1) nanocrystalline Pd nanowires (grain diameter
      approximately 5 nm, henceforth nc5-Pd) and (2) nanocrystalline Pd nanowires with
      a grain diameter of 15 nm (nc15-Pd). These nanowires were evaluated for the
      detection of hydrogen gas (H(2)). Despite their fundamental similarities, the
      behavior of these nanowires upon exposure to H(2) was dramatically and
      reproducibly different: nc5-Pd nanowires spontaneously fractured upon exposure to
      H(2) above 1-2%. Fractured nanowires continued to function as sensors for H(2)
      concentrations above 2%, actuated by the volume change associated with the alpha
      to beta phase transition of PdH(x). nc15-Pd nanowires, in contrast, withstood
      repeated exposures to H(2) up to 10% without fracturing. nc15-Pd nanowires showed
      a rapid (2 s at 10%) increase in resistance in the presence of H(2) and a
      response that scaled smoothly with [H(2)] spanning 5 orders of magnitude down to
      2 ppm.

PMID- 19391611
TI  - Demonstration of nanofocusing by the use of plasmonic lens illuminated with
      radially polarized light.
AB  - We experimentally demonstrate the focusing of surface plasmon polaritons by a
      plasmonic lens illuminated with radially polarized light. The field distribution
      is characterized by near-field scanning optical microscope. A sharp focal spot
      corresponding to a zero-order Bessel function is observed. For comparison, the
      plasmonic lens is also measured with linearly polarized light illumination,
      resulting in two separated lobes. Finally, we verify that the focal spot
      maintains its width along the optical axis of the plasmonic lens. The results
      demonstrate the advantage of using radially polarized light for nanofocusing
      applications involving surface plasmon polaritons.

PMID- 19391612
TI  - Combining pattern instability and shape-memory hysteresis for phononic switching.
AB  - We report a fully reversible and robust shape-memory effect in a two-dimensional
      nanoscale periodic structure composed of three steps, the elastic instability
      governing the transformation, the plasticity that locks in the transformed
      pattern as a result of an increase in glass transition temperature (T(g)), and
      the subsequent elastic recovery due to the vapor-induced decrease in T(g).
      Solvent swelling of a cross-linked epoxy/air cylinder structure induces an
      elastic instability that causes a reversible change in the shape of the void
      regions from circular to oval. The pattern symmetry changes from symmorphic p6mm
      to nonsymmorphic p2gg brought via the introduction of new glide symmetry elements
      and leads to a significant change in the phononic band structure, specifically in
      the opening of a new narrow-band gap due to anticrossing of bands, quite distinct
      from gaps originating from typical Bragg scattering. We also demonstrate that
      numerical simulations correctly capture the three steps of the shape-memory cycle
      observed experimentally.

PMID- 19391613
TI  - Total synthesis of (3R,3'R,6'R)-lutein and its stereoisomers.
AB  - (3R,3'R,6'R)-lutein (1) is a major dietary carotenoid that is abundant in most
      fruits and vegetables commonly consumed in the U.S. and that accumulates in the
      human plasma, major organs, and ocular tissues. Numerous epidemiological and
      experimental studies have shown that 1 has important biological activities and
      may play an important role in the prevention of age-related macular degeneration
      (AMD). While the total synthesis of 1 has been previously reported in a poor
      overall yield, the total synthesis of the other seven stereoisomers of lutein has
      not yet been accomplished. We have developed a relatively straightforward
      methodology for the total synthesis of 1 and three of its stereoisomers,
      (3R,3'S,6'S)-lutein (2), (3R,3'S,6'R)-lutein or 3'-epilutein (3), and
      (3R,3'R,6'S)-lutein (4) by C(15) + C(10) + C(15) Wittig coupling reactions.
      Employing this methodology, the other four stereoisomers of lutein that are
      enantiomeric to the aforementioned lutein isomers can be similarly prepared. One
      of the important features of this strategy is its application to the total
      synthesis of (13)C-labeled luteins and their metabolites with appropriate
      stereochemistry for metabolic studies in animals and humans. This synthesis also
      provides access to the C(15)-precursors of optically active carotenoids with a 3
      hydroxy-epsilon end group that are otherwise difficult to synthesize.

PMID- 19391614
TI  - A convergent route for the total synthesis of malyngamides O, P, Q, and R.
AB  - A convergent, enantioselective and general synthetic route to a class of marine
      natural products-malyngamides O (1), P (2), Q (3), R (4), 5''-epi-3 and 5''-epi-4
      bearing a novel vinyl chloride structural motif was developed. The key steps
      involved construction of the vinyl chloride functionality by Wittig reaction, a
      DCC/HOBt-promoted amidation, an aldol reaction in the construction of the basic
      backbone of 1, 2, 3, 4, 5''-epi-3, and 5''-epi-4, and methylation of an enol
      moiety via either base/acid conditions or a Mitsunobu reaction. Moreover, the
      absolute configuration of the stereogenic center at C-5'' in 3 was further
      confirmed by synthesis of the natural product and its C-5'' epimer.

PMID- 19391615
TI  - Expeditious synthesis of contorted hexabenzocoronenes.
AB  - Contorted hexabenzocoronenes (HBCs) have been synthesized in an expedited manner
      utilizing a double Barton-Kellogg olefination reaction and a subsequent Scholl
      cyclization. The scope of both transformations was investigated using a series of
      pentacene quinones and double olefin precursors. The utility of these reactions
      to help create functionalized and oligomeric HBCs in a rapid manner is
      demonstrated.

PMID- 19391616
TI  - Meehanines A-K, spermidine alkaloidal glycosides from Meehania urticifolia.
AB  - From the whole plant of Meehania urticifolia, 11 new spermidine alkaloidal
      glycosides, meehanines A-K (1-11), were isolated. The structures of these new
      compounds were elucidated on the basis of the results of spectroscopic data
      analysis.

PMID- 19391617
TI  - Catalytic, one-pot synthesis of beta-amino acids from alpha-amino acids.
      Preparation of alpha,beta-peptide derivatives.
AB  - The one-pot conversion of readily available alpha-amino acid into beta-amino acid
      derivatives was carried out in good yields. The method is a sequential process
      initiated by a tandem radical decarboxylation-oxidation reaction; the resulting
      acyliminium ion was trapped by silyl ketenes. Stoichiometric and catalytic
      versions of this reaction were developed and then applied to prepare modified di-
      and tripeptides. Interestingly, some tripeptides formed expanded beta-turns in
      the solid state.

PMID- 19391618
TI  - Synthesis and characterization of hyperbranched poly(glycidol) modified with pH-
      and temperature-sensitive groups.
AB  - Hyperbranched poly(glycidol)s with varying degrees of polymerization were
      modified by reaction with succinic anhydride and isopropylamine to obtain novel
      pH- and thermosensitive polymers. These polymers exhibited phase transitions in
      response to decreasing pH and/or increasing temperature, depending on the degree
      of polymerization and the ratio of succinyl group to N-isopropylamide. It was
      possible to harvest a bioactive molecule, rose bengal, from solution using the
      phase transition of thermosensitive hyperbranched poly(glycidol).

PMID- 19391619
TI  - Waiting time dynamics in two-dimensional infrared spectroscopy.
AB  - We review recent work on the waiting time dynamics of coherent two-dimensional
      infrared (2DIR) spectroscopy. This dynamics can reveal chemical and physical
      processes that take place on the femto- and picosecond time scale, which is
      faster than the time scale that may be probed by, for example, nuclear magnetic
      resonance spectroscopy. A large number of chemically relevant processes take
      place on this time scale. Such processes range from forming and breaking hydrogen
      bonds and proton transfer to solvent exchange and vibrational population
      transfer. In typical 2DIR spectra, multiple processes contribute to the waiting
      time dynamics and the spectra are often congested. This makes the spectra
      challenging to interpret, and the aid of theoretical models and simulations is
      often needed. To be useful, such models need to account for all dynamical
      processes in the sample simultaneously. The numerical integration of the
      Schrodinger equation (NISE) method has proven to allow for a very general
      treatment of the dynamical processes. It accounts for both the motional narrowing
      resulting from solvent-induced frequency fluctuations and population transfer
      between coupled vibrations. At the same time, frequency shifts arising from
      chemical-exchange reactions and changes of the transition dipoles because of
      either non-Condon effects or molecular reorientation are included in the
      treatment. This method therefore allows for the disentanglement of all of these
      processes. The NISE method has thus far been successfully applied to study
      chemical-exchange processes. It was demonstrated that 2DIR is not only sensitive
      to reaction kinetics but also to the more detailed reaction dynamics. NISE has
      also been applied to the study of population transfer within the amide I band (CO
      stretch) and between the amide I and amide II bands (CN stretch and NH bend) in
      polypeptides. From the amide I studies, it was found that the population transfer
      can be used to enhance cross-peaks that act as structural markers for beta-sheet
      structure in proteins. From the amide I/II investigation, it was found that the
      amide II band and the hydrogen-bond stretch vibration are important parts of the
      relaxation pathway for the amide I vibration. With the development of simple
      approximations, it becomes possible to apply the NISE method even to very big
      systems, such as the OH stretch of bulk water, which can only be described well
      when large numbers of coupled vibrations are taken into account.

PMID- 19391620
TI  - Cyclic and multicyclic polymers by three-dimensional polycondensation.
AB  - The recent confirmation that polycondensations (and other step-growth
      polymerizations) of difunctional monomers involve cyclization reactions at any
      concentration and at any stage of the polymerization also has consequences for
      three-dimensional polycondensations on multifunctional monomers. It is
      demonstrated that tree-shaped (hyperbranched) oligomers are gradually transformed
      into star-shaped polymers with a cyclic core, when the conversion increases.
      Polycondensations of "a(2) + b(3)" or "a(2) + b(4)" monomer combinations yield
      multicyclic polymers, when gelation can be avoided. This new architecture may be
      subdivided into three groups: perfect multicycles free of functional groups,
      multicycles having b functions, and multicycles having "a" groups. The concrete
      examples discussed in this Account mainly concern polyethers and polyesters.

PMID- 19391621
TI  - Structural basis for iron mineralization by bacterioferritin.
AB  - Ferritin proteins function to detoxify, solubilize and store cellular iron by
      directing the synthesis of a ferric oxyhydroxide mineral solubilized within the
      protein's central cavity. Here, through the application of X-ray crystallographic
      and kinetic methods, we report significant new insight into the mechanism of
      mineralization in a bacterioferritin (BFR). The structures of nonheme iron-free
      and di-Fe(2+) forms of BFR showed that the intrasubunit catalytic center, known
      as the ferroxidase center, is preformed, ready to accept Fe(2+) ions with little
      or no reorganization. Oxidation of the di-Fe(2+) center resulted in a di-Fe(3+)
      center, with bridging electron density consistent with a mu-oxo or hydro bridged
      species. The mu-oxo bridged di-Fe(3+) center appears to be stable, and there is
      no evidence that Fe(3+)species are transferred into the core from the ferroxidase
      center. Most significantly, the data also revealed a novel Fe(2+) binding site on
      the inner surface of the protein, lying approximately 10 A directly below the
      ferroxidase center, coordinated by only two residues, His46 and Asp50. Kinetic
      studies of variants containing substitutions of these residues showed that the
      site is functionally important. In combination, the data support a model in which
      the ferroxidase center functions as a true catalytic cofactor, rather than as a
      pore for the transfer of iron into the central cavity, as found for eukaryotic
      ferritins. The inner surface iron site appears to be important for the transfer
      of electrons, derived from Fe(2+) oxidation in the cavity, to the ferroxidase
      center. Bacterioferritin may represent an evolutionary link between ferritins and
      class II di-iron proteins not involved in iron metabolism.

PMID- 19391623
TI  - N doping of oxide nanosheets.
AB  - Photo-N doping for Nb-O system oxide nanosheets such as Nb(6)O(17), TINbO(5), and
      Ca(2)Nb(3)O(10) was succeeded in by treatment under mild conditions, where their
      H-restacked forms containing tetrabuthylammonium (TBA) ion were illuminated by UV
      light at room temperature. A relatively strong absorption in visible light region
      (400 approximately 600 nm) was observed for the N-doped samples because of
      formation of p-band or valence band hybridization of N in the Nb-O bandgap. The N
      doping proceeded only under TBA presence in water without O(2), and Pt loading
      promoted this doping reaction. It is proposed as a mechanism from the results of
      the doping for the Ti-O and Nb-O nanosheet mixed samples, that the Nb-O nanosheet
      acts as a photocatalyst for the N-doping reaction. This is the first report of N
      doping to oxide nanosheets.

PMID- 19391622
TI  - Prediction of the rotational tumbling time for proteins with disordered segments.
AB  - For well-structured, rigid proteins, the prediction of rotational tumbling time
      (tau(c)) using atomic coordinates is reasonably accurate, but is inaccurate for
      proteins with long unstructured sequences. Under physiological conditions, many
      proteins contain long disordered segments that play important regulatory roles in
      fundamental biological events including signal transduction and molecular
      recognition. Here we describe an ensemble approach to the boundary element method
      that accurately predicts tau(c) for such proteins by introducing two layers of
      molecular surfaces whose correlated velocities decay exponentially with distance.
      Reliable prediction of tau(c) will help to detect intra- and intermolecular
      interactions and conformational switches between more ordered and less ordered
      states of the disordered segments. The method has been extensively validated
      using 12 reference proteins with 14 to 103 disordered residues at the N- and/or C
      terminus and has been successfully employed to explain a set of published results
      on a system that incorporates a conformational switch.

PMID- 19391624
TI  - Characterization of the intense pigment tomato genotype emphasizing targeted
      fruit metabolites and chloroplast biogenesis.
AB  - The tomato INTENSE PIGMENT (IP) genotype is characterized by intense visual
      pigmentation of unripe and ripe fruits, not thoroughly analyzed thus far. This
      study was therefore designed to analyze key morphologic, metabolomic, and
      photomorphogenic phenotypes of this genotype in comparison to its near-isogenic
      normal counterpart and to evaluate its significance relative to other tomato
      mutants known for increased fruit pigmentation. The IP genotype produced smaller
      and darker red fruits, and a substantially increased chloroplast biogenesis was
      found in its green fruit and leaf tissues. Ripe-red fruits of the IP genotype
      produced 34-38% more soluble solids and up to 62.6% more carotenoids, but no
      differences were found in the concentration of flavonoid compounds in its peel
      tissue. The IP genotype was found to display a greater hypocotyl inhibition
      response to blue and yellow light, but a more prominent and novel response to
      total darkness. As a whole, the IP genotype exhibited highly desirable traits,
      making it a valuable genotype for tomato breeders attempting to introduce
      functional and taste qualities into tomato fruits.

PMID- 19391625
TI  - A computational study of electronic and spectroscopic properties of formic acid
      dimer isotopologues.
AB  - We consider the effect of isotopic labeling on the electric charge distribution
      and dynamics of the formic acid dimer. Our investigation is based on accurate ab
      initio calculations of vibrationally induced dipole moments and multidimensional
      quantum calculations of vibrational ground-state splittings. It is found that non
      negligible dipole moments of mu = 0.032 D and mu = 0.021 D arise in HCOOH-DOOCD
      and HCOOH-DOOCH, respectively, suggesting the feasibility of microwave studies.
      Within the reaction surface Hamiltonian approach a ratio of splittings of
      1:0.2:0.045 is predicted for HCOOH-HOOCH:HCOOH-DOOCH:HCOOD-DOOCH.

PMID- 19391626
TI  - Cyclometalated 6-phenyl-2,2'-bipyridyl (CNN) platinum(II) acetylide complexes:
      structure, electrochemistry, photophysics, and oxidative- and reductive-quenching
      studies.
AB  - Three cyclometalated 6-phenyl-4-(p-R-phenyl)-2,2'-bipyridyl (CNN-Ph-R) Pt(II)
      acetylide complexes, Pt(CNN-Ph-R)(CCPh), where R = Me (1), COOMe (2), and
      P(O)(OEt)(2) (3), have been synthesized and studied. Compounds 1 and 3 have been
      structurally characterized by single crystal X-ray crystallography and are found
      to exhibit distorted square planar geometries about the Pt(II) ions. The
      electrochemical properties of the compounds, as determined by cyclic voltammetry,
      have also been examined. Complexes 1-3 are brightly emissive in fluid CH(2)Cl(2)
      solution and in the solid state with lambda(em)(max) of ca. 600 nm and lifetimes
      on the order of ca. 500 ns in fluid solution. The emissions are assigned to a
      (3)MLCT transition. The complexes undergo oxidative quenching by MV(2+) with
      quenching rates near the diffusion-controlled limit (k(q) approximately 1.4 x
      10(10) M(-1) s(-1)) in CH(2)Cl(2) solution. Reductive-quenching experiments of
      complexes 1-3 by the amine donors N,N,N',N'-tetramethylphenylenediamine (TMPD),
      phenothiazine (PTZ), and N,N,N',N'-tetramethylbenzidine (TMB) follow Stern-Volmer
      behavior, with very fast quenching rates on the order of 10(9)-10(10) M(-1) s(-1)
      in CH(2)Cl(2) solution. When the complexes are employed as the sensitizer in
      multiple component systems containing MV(2+), TEOA, and colloidal Pt in aqueous
      media, approximately one turnover of H(2) (TN vs mol of chromophore) is produced
      per hour upon irradiation with lambda > 410 nm but only after at least a 2 h
      induction period.

PMID- 19391627
TI  - Syntheses and vibrational circular dichroism spectra of the complete series of
      [Ru((-)- or (+)-tfac)(n)(acac)(3-n)] (n = 0 approximately 3, tfac = 3
      trifluoroacetylcamphorato and acac = acetylacetonato).
AB  - Twenty four kinds of Ru(III) complexes expressed by the formula of Delta- or
      Lambda-[Ru((-)- or (+)-tfac)(n)(acac)(3-n)] (n = 1, 2, and 3, (-)- or (+)-tfac =
      (-)- or (+)-3-trifluoroacetylcamphorato and acac = acetylacetonato) were prepared
      in a pure diastereomeric form. The separation of these diastereomers was
      accomplished chromatographically by rational use of two antipodal chiral columns.
      The separated complexes were identified by means of mass spectra, (1)H NMR,
      electronic circular dichroism, and partly X-ray diffraction analyses. When a pair
      of Delta- and Lambda-[Ru(acac)(3)] (n = 0) was added to this group, they
      constituted the complete series of mixed ligand complexes including ligand
      chirality under the condition of no mixing of chiral ligands. The vibrational
      circular dichroism (VCD) spectra of their CDCl(3) solutions were recorded in the
      wavenumber region of 1000 approximately 1800 cm(-1). The results provided a
      benchmark for systematically examining the effects of the stereochemical
      properties on VCD spectra such as the degree of ligand substitution, DeltaLambda
      configurations, geometrical isomerism, and ligand chirality. As a result, the
      geometrical isomers of trans- or cis-[Ru((-)- or (+)-tfac)(2)(acac)] and mer- or
      fac-[Ru((-)- or (+)-tfac)(3)] were clearly differentiated by their VCD signals,
      which was hardly possible from their IR spectra alone.

PMID- 19391628
TI  - A computational study of the hydrolysis of dGTP analogues with halomethylene
      modified leaving groups in solution: implications for the mechanism of DNA
      polymerases.
AB  - DNA polymerases make up a family of enzymes responsible for regulating DNA
      replication and repair, which in turn maintains the integrity of the genome.
      However, despite intensive kinetic, crystallographic, and computational studies,
      elucidation of the detailed enzymatic mechanism still presents a significant
      challenge. We recently developed an alternative strategy for exploring the
      fidelity and mechanism of DNA polymerases, by probing leaving group effects on
      nucleotidyl transfer using a series of dGTP bisphosphonate analogues in which the
      beta,gamma-bridging oxygen was replaced by a series of substituted methylene
      groups (X = CYZ, where Y and Z = H, halogen, or another substituent). Pre-steady
      state kinetic measurements of DNA polymerase-catalyzed incorporation of correctly
      base paired (R) and mispaired (W) analogues demonstrated a strong linear free
      energy relationship (LFER) between the polymerase rate constant (k(pol)) and the
      highest pK(a) of the free bisphosphonic acid corresponding to the leaving group.
      However, unexpectedly, the data segregated into two distinctly different linear
      correlations depending on the nature of the substituent. The discrepancy between
      the two lines was considerably greater when the dGTP analogue formed an incorrect
      (G.T) rather than a correct (G.C) base pair, although the reason for this
      phenomenon remains unexplained. Here, we have evaluated the complete free energy
      surfaces for bisphosphonate hydrolysis in aqueous solution and evaluated the
      corresponding LFER. Our study, which employs several alternative solvation
      models, finds a split of the calculated LFER for the mono- and dihalogen
      compounds into two parallel lines, reflecting their behavior in the polymerase
      catalyzed condensation reaction. We suggest that the division into two linear
      subsets may be a generalized solvation phenomenon involving the overall
      electrostatic interaction between the substrates and their surroundings and would
      also be observed in polar solvents in the absence of the enzyme, if the reaction
      in solvent is in fact identical to that of the enzyme. However, the amplified
      differences between the LFER lines for the incorporation of matched and
      mismatched deoxynucleotides probably reflects the differences in the
      electrostatic interaction between the TS charges in the polymerase active site.
      An understanding of the mechanism of this reaction in solution could thereby
      provide a steppingstone for understanding the factors governing the fidelity of
      DNA polymerases.

PMID- 19391629
TI  - Influence relevance voting: an accurate and interpretable virtual high throughput
      screening method.
AB  - Given activity training data from high-throughput screening (HTS) experiments,
      virtual high-throughput screening (vHTS) methods aim to predict in silico the
      activity of untested chemicals. We present a novel method, the Influence
      Relevance Voter (IRV), specifically tailored for the vHTS task. The IRV is a low
      parameter neural network which refines a k-nearest neighbor classifier by
      nonlinearly combining the influences of a chemical's neighbors in the training
      set. Influences are decomposed, also nonlinearly, into a relevance component and
      a vote component. The IRV is benchmarked using the data and rules of two large,
      open, competitions, and its performance compared to the performance of other
      participating methods, as well as of an in-house support vector machine (SVM)
      method. On these benchmark data sets, IRV achieves state-of-the-art results,
      comparable to the SVM in one case, and significantly better than the SVM in the
      other, retrieving three times as many actives in the top 1% of its prediction
      sorted list. The IRV presents several other important advantages over SVMs and
      other methods: (1) the output predictions have a probabilistic semantic; (2) the
      underlying inferences are interpretable; (3) the training time is very short, on
      the order of minutes even for very large data sets; (4) the risk of overfitting
      is minimal, due to the small number of free parameters; and (5) additional
      information can easily be incorporated into the IRV architecture. Combined with
      its performance, these qualities make the IRV particularly well suited for vHTS.

PMID- 19391630
TI  - Structure-based CoMFA as a predictive model - CYP2C9 inhibitors as a test case.
AB  - In this study, we tried to establish a general scheme to create a model that
      could predict the affinity of small compounds to their target proteins. This
      scheme consists of a search for ligand-binding sites on a protein, a generation
      of bound conformations (poses) of ligands in each of the sites by docking,
      identifications of the correct poses of each ligand by consensus scoring and MM
      PBSA analysis, and a construction of a CoMFA model with the obtained poses to
      predict the affinity of the ligands. By using a crystal structure of CYP 2C9 and
      the twenty known CYP inhibitors as a test case, we obtained a CoMFA model with a
      good statistics, which suggested that the classification of the binding sites as
      well as the predicted bound poses of the ligands should be reasonable enough. The
      scheme described here would give a method to predict the affinity of small
      compounds with a reasonable accuracy, which is expected to heighten the value of
      computational chemistry in the drug design process.

PMID- 19391631
TI  - Docking ligands into flexible and solvated macromolecules. 3. Impact of input
      ligand conformation, protein flexibility, and water molecules on the accuracy of
      docking programs.
AB  - Several modifications and additions to Fitted1.5 led to the development of
      Fitted2.6. Among the novel implementations are a matching algorithm-enhanced
      genetic algorithm and a ring conformational search algorithm. With these various
      optimizations, we also hoped to remove the biases and to develop a docking
      program that would provide results (i.e., poses) as independent as possible to
      the input ligand and protein conformations and used parameters, although keeping
      the options to provide additional experimental information. These biases were
      investigated within Fitted2.6 along with FlexX, GOLD, Glide, and Surflex. The
      input ligand conformation was found to have a major impact on the program
      accuracy as drops as large as 10-50% were observed with all the programs but
      Fitted. This comparative study also demonstrates that the accuracy of Fitted is
      similar to that of other widely used programs. We have also demonstrated that
      protein flexibility, displaceable water molecules, and ring conformational search
      algorithms, three of the main Fitted features, significantly increased its
      accuracy. Finally, we also proposed potential modifications to the available
      programs to further improve their accuracy in binding mode prediction.

PMID- 19391632
TI  - Extraction and analysis of chemical modification patterns in drug development.
AB  - Most drugs have been continuously modified from prototypic compounds in the drug
      development process. Such chemical modifications in the history of drug
      development are expected to contain a wealth of medicinal chemists' knowledge,
      and the KEGG DRUG structure maps have been compiled to capture this knowledge.
      Here we attempted to extract the information on the chemical modification
      patterns from 3745 approved drugs in the KEGG DRUG database and 255 drug pairs in
      the KEGG DRUG structure maps. We first identified 236 core structures and 506
      peripheral fragments from the KEGG DRUG database using bit-represented
      fingerprints and hierarchical clustering of similar structures. We then examined
      position-dependent relationships between core structures and peripheral
      fragments, which revealed the tendency of specific fragments connected to
      specific modification sites on the core structures. Next we converted the drug
      pairs into 204 peripheral fragment changes at the modification sites. Each change
      was represented by the transformation profile defined as a difference of
      fingerprint bit patterns, and the hierarchical clustering of similar
      transformation profiles was performed. We thus identified 125 chemical
      modification patterns that characterize the KEGG DRUG structure maps. These
      patterns were further applied to the reconstruction of a new structure map. The
      approach presented here may be applicable to systematic in silico drug
      modifications.

PMID- 19391633
TI  - Yttrium complexes supported by linked bis(amide) ligand: synthesis, structure,
      and catalytic activity in the ring-opening polymerization of cyclic esters.
AB  - A series of new yttrium complexes supported by the bulky enediamido dianionic
      ligand DAB(2-) (DAB(2-) = (2,6-C(6)H(3)iPr(2))NC(Me)=C(Me)N(2,6-C(6)H(3)iPr(2))(2
      )), that is, {DAB}Y(THF)(2)(mu-Cl)(2)Li(THF)(2) (1), {DAB}Y(OtBu)(THF)(DME) (2),
      and {{DAB}Y(BH(4))(2)}{Li(DME)(3)} (3), was synthesized by salt metathesis. The
      complexes were isolated after recrystallization in 73, 66, and 52% yield,
      respectively, and characterized in solution by NMR and in the solid state by
      single-crystal X-ray diffraction studies. In complex 1, the DAB(2-) ligand is
      bonded to the metal center via two covalent YN bonds, while in complexes 2 and 3
      additional eta(2)-coordination of the C=C bond to the metal atom is observed,
      both in solution and in the solid state. The tert-butoxide and borohydride
      complexes 2 and 3 act as monoinitiators for the room temperature ring-opening
      polymerization of racemic lactide and beta-butyrolactone, providing atactic
      polymers with controlled molecular weights and relatively narrow polydispersities
      (M(w)/M(n) = 1.15-1.82). Effectively immortal ROP of lactide with as many as 50
      equiv of isopropanol per metal center was performed using complex 2 as the
      catalyst.

PMID- 19391634
TI  - Proteochemometric modeling of drug resistance over the mutational space for
      multiple HIV protease variants and multiple protease inhibitors.
AB  - The main therapeutic targets in HIV are its protease and reverse transcriptase. A
      major problem in treatment of HIV is the ability of the virus to develop drug
      resistance by accumulating mutations in its targets. Acquiring detailed
      understanding of the molecular mechanisms for the interactions of drugs with
      mutated variants of the HIV virus is mandatory to be able to design inhibitors
      that can evade the resistance. Here we have used proteochemometric modeling to
      simultaneously analyze the interactions of 21 protease inhibitors with 72 unique
      protease variants. Inhibition data (pK(i)) were correlated to descriptions of
      chemical and structural properties of the inhibitors and proteases. The
      proteochemometric model obtained showed excellent fit and predictive ability
      (R(2)=0.92, Q(2)=0.83, Q(2)(inh)=0.78) and provided quantitative assessments for
      the contribution of each mutation and their combinations to the decrease in
      inhibitor activity, both for the whole compounds series as well as for individual
      compounds. The model revealed the most deleterious mutations in the protease to
      be D30N, V32I, G48V, I50V, I54V, V82A, I84V, and L90M. The model was further used
      to identify molecular properties of chemical compounds that are important for
      their inhibition of multimutated protease variants. Our results give directions
      how to design novel improved inhibitors.

PMID- 19391636
TI  - How well do we communicate autopsy findings to next of kin?

PMID- 19391639
TI  - Proceedings of the College of American Pathologists Futurescape of Pathology
      Conference. Rosemont, Illinois. June 7-8, 2008.

PMID- 19391638
TI  - Necessity of surgical excision for atypical lobular hyperplasia and lobular
      carcinoma in situ.

PMID- 19391640
TI  - Futurescape of Pathology 2008 Conference: welcome and introductory comments.

PMID- 19391641
TI  - Keynote address--the innovator's prescription: an examination of the future of
      health care through the lenses of disruptive innovation.

PMID- 19391642
TI  - Transforming pathology: ingredients for change--the view from a chef's husband.

PMID- 19391643
TI  - Systems approach to the practice of pathology: a new role for the pathologist.

PMID- 19391644
TI  - Personalized medicine and pathology: friend or foe?

PMID- 19391645
TI  - Biomarkers in anatomic pathology: adding value to diagnosis.

PMID- 19391646
TI  - Arrays and medical microbiology: e pluribus unum.

PMID- 19391647
TI  - Medical imaging workstations: what is missing and what is coming?

PMID- 19391648
TI  - Pathology and imaging in biomarker development.

PMID- 19391649
TI  - From the incandescent light bulb to digital pathology: corporate innovation as an
      engine for change.

PMID- 19391650
TI  - Integrated diagnostics and the future of health care: corporate innovation as an
      engine for change.

PMID- 19391651
TI  - Digital pathology at the crossroads of major health care trends: corporate
      innovation as an engine for change.

PMID- 19391652
TI  - Driving to pathology's future: corporate innovation as an engine for change.

PMID- 19391653
TI  - Corporate innovation as an engine for change: panel discussion.

PMID- 19391654
TI  - Morphogenomics and morphoproteomics: a role for anatomic pathology in
      personalized medicine.

PMID- 19391655
TI  - Risks and rewards of pathology innovation: the academic pathology department as a
      business incubator.

PMID- 19391656
TI  - Pathology and radiology beyond looking at pictures.

PMID- 19391657
TI  - Infusion centers: opportunities for financial and personal success.

PMID- 19391658
TI  - Practice evolution: decentralized computer-assisted immunohistochemical image
      analysis.

PMID- 19391659
TI  - Reengineered workflow in the anatomic pathology laboratory: costs and benefits.

PMID- 19391660
TI  - The role of pathologists in the era of personalized medicine.

PMID- 19391661
TI  - Genetic heterogeneity in HER2 testing in breast cancer: panel summary and
      guidelines.
AB  - CONTEXT: Intratumoral heterogeneity of HER2 gene amplification has been well
      documented and represents subclonal diversity within the tumor. The reported
      incidence of intratumor HER2 amplification genetic heterogeneity ranges in the
      literature from approximately 5% to 30%. The presence of HER2 genetic
      heterogeneity may increase subjectivity in HER2 interpretation by the
      pathologist. OBJECTIVES: To define HER2 genetic heterogeneity and to provide
      practice guidelines for examining and reporting breast tumors with genetic
      heterogeneity for improvement of HER2 testing in breast cancer. DESIGN: We
      convened an expert panel to discuss HER2 gene amplification testing by
      fluorescence in situ hybridization. Components addressed included a definition of
      HER2 amplification heterogeneity, practice guidelines for examination of the
      tissue, and reporting criteria for this analysis. RESULTS: Genetic heterogeneity
      for amplification of HER2 gene status in invasive breast cancer is defined and
      guidelines established for assessing and reporting HER2 results in these cases.
      These guidelines are additive to and expand those published in 2007 by the
      American Society of Clinical Oncology and the College of American Pathologists.
      CONCLUSION: Standardized methods for analysis will improve the accuracy and
      consistency of interpretation of HER2 gene amplification status in breast cancer.

PMID- 19391662
TI  - College of American Pathologists considerations for the delineation of pathology
      clinical privileges.
AB  - CONTEXT: The Joint Commission (JC) established new medical staff privileging
      requirements effective January 2008. The new requirements include the development
      of ongoing professional practice evaluation (OPPE) and focused professional
      practice evaluation (FPPE) processes and incorporate the general competencies of
      patient care, medical knowledge, practice-based learning and improvement,
      interpersonal and communication skills, professionalism and systems-based
      practice jointly developed by the Accreditation Council for Graduate Medical
      Education (ACGME) and the American Board of Medical Specialties (ABMS). The
      College of American Pathologists makes resources available to assist members and
      their facilities in implementing the new requirements and improving patient care.
      OBJECTIVES: To review the general requirements for privileging and identify how
      they may apply to pathologists, to identify currently available activities and
      metrics that may be useful in addressing these requirements, and to present
      identified concepts, activities, and metrics for consideration by pathologists
      and hospitals for their adaptation into the policies and procedures that address
      the new JC physician privileging requirements. DESIGN: Review available pathology
      privileging documentation that addressed the previous JC requirements, review the
      new requirements, and search for and review available and applicable resources,
      activities, and metrics. RESULTS: Common pathology activities and metrics can be
      incorporated into the privileging processes. Current and new activities and
      metrics can be incorporated or developed to address the 6 ACGME/ABMS "General
      Competencies." CONCLUSION: Each hospital has unique privileging and physician
      evaluation requirements. Providing concepts, activities, and metrics for
      pathologists and hospitals to consider in pathology privileging will help
      implement the OPPE and FPPE processes and meet medical staff privileging
      requirements.

PMID- 19391663
TI  - Fatal head injury in children younger than 2 years in New York City and an
      overview of the shaken baby syndrome.
AB  - CONTEXT: Shaken baby syndrome is a controversial topic in forensic pathology.
      Some forensic pathologists state that shaking alone is insufficient to explain
      death and that an impact must have occurred even if there is no impact site on
      the head. OBJECTIVE: To examine a large cohort of fatal, pediatric head injuries
      for patterns of specific autopsy findings and circumstances that would support or
      dispute pure shaking as the cause of death. DESIGN: We retrospectively reviewed
      59 deaths due to head injuries in children younger than 2 years certified in our
      office during a 9 year period (1998-2006). The review included autopsy,
      toxicology, microscopy, neuropathology, and police and investigators' reports.
      RESULTS: There were 46 homicides, 8 accidents, and 1 undetermined death from
      blunt-impact injury of the head. In 10 (22%) of the homicides, there was no
      impact injury to the head, and the cause of death was certified as whiplash
      shaking. In 4 (40%) of these 10 deaths, there was a history of shaking. In 5
      (83%) of the other 6, there was no history of any purported accidental or
      homicidal injury. All 8 accidental deaths had impact sites. Of the 59 deaths, 4
      (6.7%) had only remote injuries (chronic subdural hematomas, remote long bone
      fractures) that were certified as undetermined cause and manner. These 4 deaths
      were excluded from the study. CONCLUSIONS: We describe a subset of fatal,
      nonaccidental head-injury deaths in infants without an impact to the head. The
      autopsy findings and circumstances are diagnostic of a nonimpact, shaking
      mechanism as the cause of death. Fatal, accidental head injuries in children
      younger than 2 years are rare.

PMID- 19391664
TI  - Relation between red blood cell distribution width and inflammatory biomarkers in
      a large cohort of unselected outpatients.
AB  - CONTEXT: A strong independent association has been recently observed between
      elevated red blood cell distribution width (RDW) and increased incidence of
      cardiovascular events. OBJECTIVE: To assess whether RDW is associated with plasma
      markers of inflammation since the mechanism(s) underlying this association remain
      unknown. DESIGN: We retrospectively analyzed results of RDW, hemoglobin, mean
      corpuscular volume, ferritin, high-sensitivity C-reactive protein (hsCRP), and
      erythrocyte sedimentation rate (ESR) in a large cohort of unselected adult
      outpatients who were consecutively referred by general practitioners for routine
      medical check-up. RESULTS: Cumulative results of RDW and other factors were
      retrieved from the database of our laboratory information system for 3845 adult
      outpatients during a 3-year period. When participants were grouped according to
      RDW quartiles, there were strong, graded increases of ESR and hsCRP (P < .001),
      both parameters being up to 3-fold higher in the fourth versus the first
      quartile. Accordingly, the percentages of those with hsCRP greater than 3 mg/L
      (from 28% to 63%; P < .001) and ESR greater than 40 mm/h (from 8% to 40%; P <
      .001) increased steadily across RDW quartiles. In multivariable regression
      analysis, ESR and hsCRP predicted RDW independently of age, sex, mean corpuscular
      volume, hemoglobin, and ferritin. CONCLUSIONS: To our knowledge, our study
      demonstrates for the first time a strong, graded association of RDW with hsCRP
      and ESR independent of numerous confounding factors. If confirmed in future
      follow-up studies, this association might provide a rationale to introduce the
      easy, inexpensive RDW in algorithms for cardiovascular risk prediction.

PMID- 19391665
TI  - Pathology of breast carcinomas after neoadjuvant chemotherapy: an overview with
      recommendations on specimen processing and reporting.
AB  - CONTEXT: Currently, more women are being treated with chemotherapy or hormonal
      agents before surgery (neoadjuvant chemoendocrine therapy) for earlier-stage
      operable breast carcinoma. The pathologic examination of these specimens can be
      quite challenging. OBJECTIVE: To give an overview of (1) pathologic changes that
      occur during treatment, (2) systems for evaluating response to treatment, and (3)
      recommendations for pathologic examination and reporting of such cases. DATA
      SOURCES: The recommendations are based on the review of selected literature on
      breast carcinoma after neoadjuvant therapy and the authors' personal experience
      with the clinical and pathologic characteristics of cases from each of the
      authors' own institutions. CONCLUSIONS: Pathologists play a key role in the
      evaluation of pathologic response, which is extremely important as a prognostic
      factor for individual patients, as a short-term endpoint for clinical trials, and
      as an adjunct for research studies. Therefore, surgical pathologists must be
      familiar with the gross examination, sampling, and reporting of breast carcinomas
      after neoadjuvant therapy.

PMID- 19391666
TI  - Primary pulmonary follicular dendritic cell neoplasm: a case report and review of
      the literature.
AB  - Follicular dendritic cell tumor (FDCT) is an uncommon neoplasm that typically
      presents as a slow-growing, painless mass without systemic symptoms.
      Histologically, FDCT is characterized as a proliferation of spindle to ovoid
      cells having plump eosinophilic cytoplasm with indistinct borders and nuclei with
      vesicular or granular chromatin and small distinct nucleoli. The
      immunohistochemical profile of FDCT includes positive staining for CD21, CD23,
      CD35, vimentin, fascin, HLA-DR, epithelial membrane antigen, clusterin, and D2
      40. Follicular dendritic cell tumor occurs primarily in lymphoid tissue; however,
      involvement of extranodal sites such as the tonsils, spleen, and gastrointestinal
      tract has been reported. Lung involvement typically represents metastatic disease
      with, to our knowledge, only 2 prior cases of extranodal primary FDCT of the lung
      reported. We report the third case of primary pulmonary FDCT arising in a 64-year
      old woman.

PMID- 19391667
TI  - Perivascular epithelioid cell tumor.
AB  - Perivascular epithelioid cell tumors are mesenchymal neoplasms defined by the
      presence of histologically and immunohistochemically distinctive perivascular
      epithelioid cells. The perivascular epithelioid cell has no known normal tissue
      counterpart and coexpresses myoid and melanocytic markers. This tumor family
      shows marked female predominance and includes angiomyolipoma, clear cell sugar
      tumor, lymphangioleiomyomatosis, and a group of rare, morphologically and
      immunophenotypically similar tumors arising at a variety of visceral and soft
      tissue sites. This latter subset has been collectively termed perivascular
      epithelioid cell tumors-not otherwise specified. They are usually composed of
      epithelioid, but occasionally spindled, cells with clear to granular eosinophilic
      cytoplasm and focal perivascular accentuation. The mainstay of treatment is wide
      excision. Although most cases are benign, a subset behaves in a malignant
      fashion. Since few malignant cases have been reported, firm criteria for
      malignancy have yet to be established. This review focuses on the perivascular
      epithelioid cell tumors-not otherwise specified subset.

PMID- 19391669
TI  - Effects of aquatic exposure to the insecticide carbaryl and density on aquatic
      and terrestrial growth and survival in American toads.
AB  - No single mechanism has been explicitly linked to explain global amphibian
      declines, but pesticides have been implicated as potential drivers. In mesocosm
      experiments, we tested the hypotheses that American toads (Bufo americanus) would
      respond differently to the insecticide carbaryl at low or high density (i.e.,
      competition) and that postmetamorphic terrestrial growth and survival would
      differ with larval exposure to pesticides and competition. Carbaryl reduced
      survival to metamorphosis and increased time to metamorphosis in the aquatic
      phase, which could have a negative impact on fitness. However, carbaryl exposure
      increased the mass at metamorphosis of toads from high-density ponds, which may
      positively affect fitness. Pond periphyton showed a short-term increase in
      abundance after carbaryl exposure, but long-term periphyton abundance was lower
      than controls. No latent effects of carbaryl were seen on toad overwinter
      survival or mass at spring emergence in the terrestrial phase, suggesting that
      initial size differences at metamorphosis were overcome. Following individuals
      through multiple life stages is important because latent effects of exposure may
      not be predictable based on metamorphic endpoints alone.

PMID- 19391670
TI  - T lymphocyte maturation is impaired in healthy young individuals carrying trisomy
      21 (Down syndrome).
AB  - Cytokine production, immune activation, T lymphocytes maturation, and serum IL-7
      concentration were examined in 24 youngsters with Down syndrome and no acquired
      diseases (healthy Down syndrome [12 prepubertal, 13 pubertal]) and 42 age- and
      gender-matched controls (20 prepubertal, 22 pubertal). Results showed that a
      complex immune and impairment is present in healthy individuals with Down
      syndrome in whom interferon gamma, interleukin (IL) IL-10 production, as well as
      serum IL-7 concentrations and activation markers-bearing T lymphocytes were
      significantly augmented. Additionally, a complex skewing of post-thymic
      lymphocyte maturation pathways was observed in patients: significant reduction of
      CD4+ and CD8+ naive (RA+CCR7+) lymphocytes, significant increase of CD4+ and CD8+
      central memory (RA-CCR7+), and terminally differentiated (TD) (RA+CCR7-)
      lymphocytes.

PMID- 19391671
TI  - Sibling relationship quality and social functioning of children and adolescents
      with intellectual disability.
AB  - We examined sibling relationships for children and adolescents with intellectual
      disability and assessed implications for their social functioning. Targets (total
      N = 212) had either intellectual disability, a chronic illness/physical
      disability, or no disability. Nontarget siblings reported on relationship
      quality, sibling interactions were observed, and teachers reported on social
      adjustment. Group comparisons highlighted the asymmetrical hierarchy and low
      conflict unique to siblings and targets with intellectual disability. Sibling
      relationships characterized by high warmth/closeness, positive affect, and few
      negative behaviors were predictive of fewer behavior problems for the targets at
      school. Both high warmth/ closeness and high conflict predicted greater social
      competence for the targets with intellectual disability, though warmth, conflict,
      and sibling management had different implications depending on the sibling's
      gender.

PMID- 19391672
TI  - Factors predictive of midlife occupational attainment and psychological
      functioning in adults with mild intellectual deficits.
AB  - The life course of individuals with mild intellectual deficits and the factors
      that account for heterogeneity in their midlife outcomes were examined. Past
      research has shown that such individuals are at risk for poor occupational
      attainment in adulthood and more compromised psychological functioning, including
      increased depression. Although predictors varied for men and women, in general
      greater midlife occupational attainment was predicted by continuation of
      education beyond high school, having role models for achievement, and social
      participation earlier in adulthood. Midlife psychological functioning was
      predicted by having role models of achievement, having discussed plans for the
      future with parents and teachers, and achievement of aspirations set in high
      school. Implications for contemporary models of transition planning are
      discussed.

PMID- 19391674
TI  - Stressful social interactions experienced by adults with mild intellectual
      disability.
AB  - Adults with intellectual disability are vulnerable to stressful social
      interactions. We determined frequency and severity of various stressful social
      interactions, identified the social partners in these interactions, and examined
      the specific interpersonal skill difficulties of 114 adults with mild
      intellectual disability. Participants' characteristic risk factors for stressful
      social interactions were also identified. Minor and unintentional negative
      actions of others had high frequency but low severity of stress. Serious and
      intentional negative actions of others had a low frequency but high severity of
      stress. Stressful social interactions with other people who have intellectual
      disability occurred frequently and had a high severity. Difficulty controlling
      aggression predicted stressful social interactions. Findings are beneficial to
      developers of interventions to decrease stressful social interactions.

PMID- 19391675
TI  - Referential communication skills of children with Williams syndrome:
      understanding when messages are not adequate.
AB  - Although children with Williams syndrome have relatively good structural language
      and concrete vocabulary abilities, they have difficulty with pragmatic aspects of
      language. To investigate the impact of pragmatic difficulties on listener-role
      referential communication, we administered a picture placement task designed to
      measure ability to verbalize message inadequacy to a speaker separated by a
      barrier. Participants were 57 children with Williams syndrome 6 to 12 years of
      age. When messages were inadequate, children verbalized that a problem was
      encountered less than half the time. The likelihood that children would indicate
      a message was insufficient and that children who verbalized message inadequacy
      also would effectively communicate the problem varied as a function of type of
      problem encountered, theory of mind knowledge, receptive vocabulary, and CA.

PMID- 19391676
TI  - Dose-response regressions for algal growth and similar continuous endpoints:
      calculation of effective concentrations.
AB  - We derive equations for the effective concentration giving 10% inhibition (EC10)
      with 95% confidence limits for probit (log-normal), Weibull, and logistic dose
      response models on the basis of experimentally derived median effective
      concentrations (EC50s) and the curve slope at the central point (50% inhibition).
      For illustration, data from closed, freshwater algal assays are analyzed using
      the green alga Pseudokirchneriella subcapitata with growth rate as the response
      parameter. Dose-response regressions for four test chemicals (tetraethylammonium
      bromide, musculamine, benzonitrile, and 4-4-(trifluoromethyl)phenoxy-phenol) with
      ranges of representative slopes at 50% response (0.54-2.62) and EC50s (2.20-357
      mg/L) were selected. Reference EC50s and EC10s with 95% confidence limits using
      probit or Weibull models are calculated by nonlinear regression on the whole
      dataset using a dose-response regression program with variance weighting and
      proper inverse estimation. The Weibull model provides the best fit to the data
      for all four chemicals. Predicted EC10s (95% confidence limits) from our derived
      equations are quite accurate; for example, with 4-4-(trifluoromethyl)phenoxy
      phenol and the probit model, we obtain 1.40 (1.22-1.61) mg/L versus 1.40 (1.20-
      1.64) mg/L obtained from the nonlinear regression program. The main advantage of
      the approach is that EC10 or ECx (where x = 1-99) can be predicted from well
      determined responses around EC20 to EC80 without experimental data in the low- or
      high-response range. Problems with the estimation of confidence interval for
      EClow,x (concentration predicted to cause x% inhibition) from algal growth
      inhibition also are addressed. Large confidence intervals may be the result of
      experimental error and lack of a well-defined reference response value.

PMID- 19391677
TI  - Trout density and health in a stream with variable water temperatures and trace
      element concentrations: does a cold-water source attract trout to increased metal
      exposure?
AB  - A history of hard-rock mining has resulted in elevated concentrations of heavy
      metals in Prickly Pear Creek (MT, USA). Remediation has improved water quality;
      however, dissolved zinc and cadmium concentrations still exceed U.S.
      Environmental Protection Agency water-quality criteria. Physical habitat,
      salmonid density, fish health, and water quality were assessed, and metal
      concentrations in fish tissues, biofilm, and macroinvertebrates were determined
      to evaluate the existing condition in the watershed. Cadmium, zinc, and lead
      concentrations in fish tissues, biofilm, and invertebrates were significantly
      greater than those at the upstream reference site and an experimental site
      farther downstream of the confluence. Fish densities were greatest, and habitat
      quality for trout was better, downstream of the confluence, where water
      temperatures were relatively cool (16 degrees C). Measures of fish health (tissue
      metal residues, histology, metallothionein concentrations, and necropsies),
      however, indicate that the health of trout at this site was negatively affected.
      Trout were in colder but more contaminated water and were subjected to increased
      trace element exposures and associated health effects. Maximum water temperatures
      in Prickly Pear Creek were significantly lower directly below Spring Creek (16
      degrees C) compared to those at an experimental site 10 km downstream (26 degrees
      C). Trout will avoid dissolved metals at concentrations below those measured in
      Prickly Pear Creek; however, our results suggest that the preference of trout to
      use cool water temperatures may supersede behaviors to avoid heavy metals.

PMID- 19391678
TI  - A fish bioassay to evaluate the toxicity associated with the ingestion of
      benzo[a]pyrene-contaminated benthic prey.
AB  - A bioassay was developed to assess the toxic effects of ingested prey
      contaminated by polycyclic aromatic hydrocarbons (PAHs) using the teleost
      Fundulus heteroclitus as a predator and the polychaete Nereis virens as a benthic
      vector. Ten groups of nine male adult Fundulus were exposed for 21 d to 10
      different diets of Nereis contaminated with benzo[a]pyrene (BaP) by spiking dead
      Nereis with BaP (spiked Nereis [SN] diets, 0-26 microg of BaP per gram dry wt) or
      by exposing living Nereis to a diet, to sediments, or to both contaminated with
      BaP (exposed Nereis [EN] diets, 0-16 microg/g dry wt). Another group was exposed
      to commercial fish food, used as reference diet. Condition and prevalence of
      histopathological changes were not affected. Exposure to the SN diets containing
      at least 3.5 microg of BaP per gram dry weight caused an induction of
      ethoxyresorufin-O-deethylase activity in the intestine but not in the liver. In
      contrast, fish exposed to the highest doses (> or = 13.4 microg of BaP per gram
      dry wt) had increased cellular proliferation rate in the liver but not in the
      intestine. Quantifiable levels of free BaP tetrol-like metabolites were detected
      in the bile of fish exposed to diets containing more than 6.8 microg/g dry weight
      of BaP, and exhibited a dose-response relationship in fish exposed to SN diets.
      For a similar dose of BaP, EN and SN diets had similar effects. Thus, the BaP
      metabolic products that could have been produced in Nereis apparently did not
      contribute to the biomarkers responses. This bioassay can be applied to a variety
      of prey contaminated naturally or experimentally with PAHs. The present study
      supports the use of intestinal biomarkers, in addition to hepatic biomarkers, in
      environmental monitoring to assess the impact of dietary exposure to PAHs.

PMID- 19391679
TI  - Global uncertainty and sensitivity analysis of a food-web bioaccumulation model.
AB  - A global uncertainty and sensitivity analysis (UA/SA) of a state-of-the-art, food
      web bioaccumulation model was carried out. We used an efficient screening
      analysis technique to identify the subset of the most relevant input factors
      among the whole set of 227 model parameters. A quantitative UA/SA was then
      applied to this subset to rank the relevance of the parameters and to partition
      the variance of the model output among them by means of a nonlinear regression of
      the outcomes of 1,000 Monte Carlo simulations. The concentrations of four
      representative persistent organic pollutants (POPs) in two representative species
      of the coastal marine food web of the Lagoon of Venice (Italy) were taken as
      model outputs. The screening analysis showed that the ranking was remarkably
      different in relation to the species and chemical being considered. The
      subsequent Monte Carlo-based quantitative analysis pointed out that the
      relationships among some of the parameters and the model outputs were nonlinear.
      The nonlinear regression showed that the fraction of output variance accounted
      for by each parameter was strongly dependent on the range of the octanol-water
      partition coefficient (K(OW)) values being considered. For the less hydrophobic
      chemicals, the main sources of model uncertainty were the parameters related to
      the respiratory bioaccumulation, whereas for the more hydrophobic ones, K(OW) and
      the other parameters related to the dietary uptake explained the largest
      fractions of the variance of the chemical concentrations in the organisms. The
      analysis highlighted that efforts are still needed for reducing uncertainty of
      model parameters to get reliable results from the application of food web
      bioaccumulation models.

PMID- 19391680
TI  - Effects of photosystem II inhibitors and their mixture on freshwater
      phytoplankton succession in outdoor mesocosms.
AB  - Effects of three photosystem II inhibitors and of their mixture on a freshwater
      phytoplankton community were studied in outdoor mesocosms. Atrazine, isoproturon,
      and diuron were applied as 30% hazardous concentrations (HC30s) obtained from
      species-sensitivity distributions. Taking concentration addition into account,
      the mixture comprised one-third of the HC30 of each substance. Effects were
      investigated during a five-week period of constant concentrations and a five
      month posttreatment period when the herbicides dissipated. Total abundance,
      species composition, and diversity and recovery of the community were evaluated.
      Ordination techniques, such as principal component analysis and principal
      response curve, were applied to compare the various treatments on the community
      level. The three herbicides stimulated comparable effects on total abundance and
      diversity of phytoplankton during the period of constant exposure because of the
      susceptibility of the dominant cryptophytes Chroomonas acuta and Cryptomonas
      erosa et ovata and the prasinophyte Nephroselmis cf. olivacea. Moreover,
      concentration addition described combined effects of atrazine, isoproturon, and
      diuron on total abundance and diversity in the constant-exposure period, because
      their mixture induced effects on abundance and diversity similar to those of the
      single substances. Principal component and principal response curve analyses
      revealed that the community structure of diuron- and isoproturon-treated
      phytoplankton recovered two weeks after constant exposure, which might be related
      to the fast dissipation of the phenylureas. Species compositions of mixture- and
      atrazine-treated communities were not comparable to that of the control community
      five months after the end of constant exposure. This might be explained by the
      slower dissipation of atrazine relative to the phenylureas and by differences in
      the species sensitivities, resulting in a different succession of phytoplankton.

PMID- 19391681
TI  - Degradation and ecotoxicity of the biomedical drug artemisinin in soil.
AB  - The plant Artemisia annua L. is cropped in many countries for production of the
      antimalarial drug artemisinin. Artemisinin is phytotoxic and has insecticidal
      activity. Large-scale cultivation of A. annua may cause transfer of artemisinin
      to soil and, hence, may affect both soil organisms and the aquatic environment if
      the compound is leachable. In the present study, a new method for extraction of
      artemisinin from soil was developed, and field concentrations and degradation
      kinetics of artemisinin in sandy and loamy soils were measured. The soil
      concentrations in a Danish A. annua field were up to 11.7 mg/kg. The degradation
      kinetics could be modeled as the sum of two first-order reactions, a fast initial
      degradation followed by a reaction that was 11- to 25-fold slower. It took at
      least 35 d before artemisinin could not be detected (<0.36 mg/kg) at 20 degrees
      C, classifying artemisinin as being relatively persistent in the environment.
      Combined with its water solubility of 49.7 +/- 3.7 mg/L, this makes it
      potentially leachable. In soil, artemisinin repelled the earthworm (Eisenia
      fetida; the 10 and 50% effect concentrations [EC10s and EC50s, respectively] were
      5.24 +/- 2.64 and 21.57 +/- 4.73 mg/kg, respectively) and inhibited growth of
      lettuce (Lactuca sativa L.; EC50, 2.48 mg/kg). Springtails (Folsomia candida)
      were not affected in the tested concentration range of 1 to 100 mg/kg.
      Artemisinin had toxicity to the freshwater algae (Pseudokirchneriella
      subcapitata; EC50, 0.24 +/- 0.01 mg/L) and duckweed (Lemna minor; EC50, 0.19 +/-
      0.03 mg/L) similar to that of the commercial herbicide atrazine. Based on the
      presented data, the risks of adverse environmental effects because of cultivation
      of A. annua are high and comparable to those when using commercial pesticides.

PMID- 19391682
TI  - Microarray analysis of polychlorinated biphenyl mixture-induced changes in gene
      expression among Atlantic tomcod populations displaying differential sensitivity
      to halogenated aromatic hydrocarbons.
AB  - Several populations of fishes inhabiting contaminated Atlantic Coast estuaries
      exhibit resistance to early life-stage (ELS) toxicities induced by halogenated
      aromatic hydrocarbons such as coplanar polychlorinated biphenyls (PCBs). These
      toxicities include mortality, circulatory failure, edema, and craniofacial
      malformations. The mechanisms behind resistance to halogenated aromatic
      hydrocarbon toxicity in these populations are unknown. First and second
      generation Atlantic tomcod Microgadus tomcod embryos derived from the Hudson
      River ([HR]; New York, USA) population are highly resistant to PCB-induced
      cytochrome P4501A (CYP1A) expression and ELS toxicity when compared to embryos of
      Miramichi River ([MR]; New Brunswick, Canada) and Shinnecock Bay ([SB]; New York,
      USA) origin. The present study sought to identify novel genes involved in
      population differences in response to PCB exposure using custom microarrays.
      Microarray probes consisted of unsequenced inserts of randomly picked clones from
      a tomcod cardiac cDNA library. Tomcod embryos from three populations (HR, MR, and
      SB) were exposed to two doses of an environmentally relevant mixture of coplanar
      PCBs and screened for dose- and population-specific patterns of gene expression.
      Clones displaying significant differences between populations exposed to the high
      dose of PCBs were identified by DNA sequencing. Of the 28 identified nonribosomal
      protein clones, none displayed expression patterns highly similar to CYP1A
      (altered in MR and SB, but not in HR). However, several transcripts representing
      biomarkers of cardiomyopathy in mammals (cardiac troponin T2, cathepsin L, and
      atrial natriuretic peptide) were differentially altered among the three tomcod
      populations by PCBs. Although the present study did not identify any novel genes
      associated with PCB resistance in tomcod, several potential molecular biomarkers
      of PCB exposure were revealed.

PMID- 19391683
TI  - Characterization of ontogenetic changes in gene expression in the fathead minnow
      (Pimephales promelas).
AB  - Recently, researchers have begun looking at changes in gene expression in the
      fathead minnow (Pimephales promelas) after contaminant exposure as a way to
      develop biomarkers of exposure and effects. However, the bulk of this research
      has been conducted on adults, with few studies focusing on early life stages.
      Expression of selected genes important in growth, development, and reproduction
      in teleosts was quantified by quantitative polymerase chain reaction during
      different developmental time periods (from 0 to 28 d postfertilization [dpf]).
      Over the developmental period studied, there was a significant up-regulation of
      growth hormone mRNA and no significant changes in the expression of insulin-like
      growth factor 1. Thyroid hormone receptors A and B were detected in 4 dpf embryos
      and their expression stayed relatively constant. The variation in cytochrome
      P45019A mRNA expression was large during the first week of development, returning
      to 0 dpf expression levels thereafter. Estrogen receptor 2B was up-regulated
      during the first three weeks postfertilization, returning to prehatch values by
      28 dpf. Expression of hydroxysteroid dehydrogenase 3B and steroidogenic acute
      regulatory protein increased after the third or fourth week postfertilization,
      respectively. Vitellogenin exhibited a large degree of variation within time
      points, especially after day 15, and a significant up-regulation for this gene
      was observed at 7 and 10 dpf. Knowledge of the normal changes in gene expression
      during embryo and larval development will allow for better experimental design
      and selection of suitable biomarkers when testing the potential toxicological
      effects of contaminants in this model fish species.

PMID- 19391684
TI  - Reproductive and developmental effects of transovarian exposure to o,p'-DDT in
      Japanese quails.
AB  - Avian species have the possible risk of embryonic exposure to persistent,
      lipophilic environmental contaminants, such as dichlorodiphenyltrichloroethane
      (DDT), by transfer of chemicals accumulated in mother birds to eggs. To model
      developmental and reproductive disorders of wild birds living in contaminated
      areas, we exposed Japanese quails in ovo to o,p'-DDT prior to incubation. A
      positive estrogenic substance diethylstilbestrol (DES; 1 and 10 ng/g of egg) and
      o,p'-DDT (1-100 microg/g of egg) were injected into the yolk before incubation.
      Treatment with o,p'-DDT (10 or 100 microg/g) but not with DES significantly
      reduced the hatchability of eggs. After sexual maturation, o,p'-DDT affected
      eggshell formation in female quails but had little influence on laying; high
      doses of o,p'-DDT significantly reduced eggshell strength, shell weight, and
      shell thickness, and several females treated with 100 microg o,p'-DDT/g laid eggs
      lacking shells. Diethylstilbestrol decreased egg production itself but had little
      effect on the eggshell. Both o,p'-DDT and DES caused dose-dependent shortening of
      the left oviduct and abnormal development of the right oviduct in females, while
      testis asymmetry was observed in males treated with a high dose of DES. In the
      uterus of the oviduct, the mRNAs for calcium-regulating factors osteopontin and
      calbindin D28K were reduced by both treatments, particularly that with o,p'-DDT.
      The results indicated that transovarian exposure to o,p'-DDT could bring about
      population declines in avian species through loss of fecundity caused by
      depression of hatchability and dysfunction of the reproductive tract.

PMID- 19391685
TI  - Seasonal changes of macroinvertebrate communities in a Western cape river, South
      Africa, receiving nonpoint-source insecticide pollution.
AB  - A field study was conducted at three different sites along the Lourens River
      (South Africa) to assess aquatic macroinvertebrate abundances and community
      structures in relation to seasonal changes in rainfall and particle-associated
      organophosphorous (OP) insecticide contamination. Redundancy analysis indicated
      OP insecticide contamination (azinphos-methyl and chlorpyrifos) as the only
      significant variable determining the community composition. Principal response
      curves indicated that the invertebrate community dynamics of the Lourens River at
      the most-contaminated site, Lourens River 3 (38 +/- 23.0 microg total OP/ kg
      suspended particles), differed significantly from the less-contaminated site,
      Lourens River 2 (8.0 +/- 4.9 microg total OP/kg in suspended particles) during
      the dry season (October-December; pesticide application period), whereas no
      difference was found during the wet season (July-September). Ephemeroptera
      abundances increased significantly (p = 0.0021) at the control site, Lourens
      River 1, from the wet to dry season, whereas abundances significantly decreased
      (p = 0.0011) at Lourens River 3. Two-by-three factorial analysis of variance
      demonstrated a significant interaction of site and season for the three most
      abundant mayfly taxa, Baetis sp., Demoreptus sp., and Castanophlebia sp.,
      confirming a possible OP effect. Lourens River 3, however, differed significantly
      from the other two sites in flow, ortho-phosphate, and algae growth, which may
      partly explain the lower abundance of sensitive species. Apart from the OP
      contamination, only flow velocities showed significant differences between the
      wet and dry season at some sites. In conclusion, the present study suggests that
      particle-associated OPs affected community structure in the Lourens River at
      levels greater than 30 microg total OP/kg, whereas levels less then 10 microg
      total OP/kg yielded no significant effects.

PMID- 19391686
TI  - Application of ecosystem-scale fate and bioaccumulation models to predict fish
      mercury response times to changes in atmospheric deposition.
AB  - Management strategies for controlling anthropogenic mercury emissions require
      understanding how ecosystems will respond to changes in atmospheric mercury
      deposition. Process-based mathematical models are valuable tools for informing
      such decisions, because measurement data often are sparse and cannot be
      extrapolated to investigate the environmental impacts of different policy
      options. Here, we bring together previously developed and evaluated modeling
      frameworks for watersheds, water bodies, and food web bioaccumulation of mercury.
      We use these models to investigate the timescales required for mercury levels in
      predatory fish to change in response to altered mercury inputs. We model declines
      in water, sediment, and fish mercury concentrations across five ecosystems
      spanning a range of physical and biological conditions, including a farm pond, a
      seepage lake, a stratified lake, a drainage lake, and a coastal plain river.
      Results illustrate that temporal lags are longest for watershed-dominated systems
      (like the coastal plain river) and shortest for shallow water bodies (like the
      seepage lake) that receive most of their mercury from deposition directly to the
      water surface. All ecosystems showed responses in two phases: A relatively rapid
      initial decline in mercury concentrations (20-60% of steady-state values) over
      one to three decades, followed by a slower descent lasting for decades to
      centuries. Response times are variable across ecosystem types and are highly
      affected by sediment burial rates and active layer depths in systems not
      dominated by watershed inputs. Additional research concerning watershed processes
      driving mercury dynamics and empirical data regarding sediment dynamics in
      freshwater bodies are critical for improving the predictive capability of process
      based mercury models used to inform regulatory decisions.

PMID- 19391687
TI  - Combined experimental and theoretical study on photoinduced toxicity of an
      anthraquinone dye intermediate to Daphnia magna.
AB  - The toxicity of chemicals can be enhanced by light through two photochemical
      pathways: Photomodification to more toxic substances and photosensitization. In
      the present study, the reactive oxygen species (ROS) mechanism for photoinduced
      acute toxicity of 1-amino-2,4-dibromoanthraquinone (ADBAQ) to Daphnia magna was
      clarified by experiment and theoretical calculation. The results of the present
      study show that ADBAQ exhibited high toxicity to D. magna under simulated solar
      radiation (SSR), with a median effective concentration of 1.23 +/- 0.19 nM (mean
      +/- standard deviation). The photomodified ADBAQ (mixtures of ADBAQ and its
      photoproducts) was less phototoxic than the intact ADBAQ. The SSR-only or ADBAQ
      only treatments did not affect the ROS level in D. magna, whereas increased ROS
      levels were observed in the presence of SSR and ADBAQ. The ROS in vivo were
      determined by measuring the fluorescence of 2',7'-dichlorofluorescein, which is a
      useful technique to assess toxicity of chemicals to aquatic organisms. The
      antioxidants, including vitamin C, vitamin E, and beta-carotene, decreased the
      photoinduced oxidative damage to D. magna, probably by scavenging ROS. These
      experimental results demonstrate that photosensitization is the potential
      mechanism of photoinduced toxicity of ADBAQ to D. magna. Proposed phototoxic
      pathways of ADBAQ were elucidated by means of time-dependent density functional
      theory. The theoretical calculation indicates that superoxide anion and singlet
      oxygen are able to be generated through electron transfer or energy transfer in
      the photosensitization reactions.

PMID- 19391688
TI  - Estimating ecotoxicological effects of pesticide drift on nontarget arthropods in
      field hedgerows.
AB  - When hedgerows grow in orchards where pesticides are applied, they can play a
      double role: Providing a barrier for chemical spray drift and as a refuge for
      beneficial arthropods such as pollinators and predators. Effectiveness of
      hedgerows as barriers to drift depends mainly on canopy density (that can be
      estimated through optical porosity) and wind speed. When optical porosity is low,
      the hedgerow can intercept a significant amount of spray drift and act as an
      effective barrier, but the intercepted pesticide can negatively affect the
      beneficial arthropods living there. A drift model was used to simulate drift in a
      hedgerow- vineyard system, and a deposition distribution model was used to
      calculate the pesticide spatial pattern distribution on a hedgerow with different
      optical porosity and wind speed conditions. The possible ecotoxicological effects
      were estimated for 28 active ingredients with different median lethal rates for
      two nontarget arthropods, Aphidius rhopalosiphi and Typhlodromus pyri. A
      spatialized risk assessment for a hedgerow is suggested to improve procedures
      based on application rate, standard drift, and vegetation distribution values, as
      in the hazard quotient approach. An alternative method for calculation of the
      exposure is also proposed, with a step-by-step example of a toxicity/exposure
      ratio calculation. The results highlighted the importance of the spatial pattern
      of drift and proved that a hedgerow can be an effective barrier against spray
      drift. Analysis of the toxicity/exposure ratio values showed that a hedgerow can
      continue its shelter and feeding function for nontarget arthropods when low
      toxicity pesticides are used, there is no significant wind interference, or both.

PMID- 19391689
TI  - Combined effect of environmental pollutants (nickel, chlorpyrifos) and
      temperature on the ground beetle, Pterostichus oblongopunctatus (Coleoptera:
      Carabidae).
AB  - Terrestrial organisms in the field often are exposed to a combination of stress
      factors of various origins, but little is known about interactions between
      different types of stressors. In the present study, we demonstrate the results of
      a study on interactions between Ni, chlorpyrifos (CPF), and temperature in the
      ground beetle, Pterostichus oblongopunctatus. The results revealed that all
      factors, and their interactions, influenced life-cycle parameters of the beetles
      (survival and reproduction). Significant three-factor interactions were found for
      effects on beetle survival, indicating that the combined negative effect of Ni
      and CPF was temperature dependent. In addition, significant effects of body mass
      were found: The survival of beetles treated with CPF and the reproduction of
      beetles exposed to Ni were positively correlated with body mass. All studied
      endpoints were affected by temperature. The results indicate that understanding
      interactions between temperature and toxicants, as well as among chemicals
      themselves, is essential for proper ecological risk assessment.

PMID- 19391690
TI  - A passive sampler based on solid-phase microextraction for quantifying
      hydrophobic organic contaminants in sediment pore water.
AB  - Sediment-quality assessment often is hindered by the lack of agreement between
      chemical and biological lines of evidence. One limitation is that the bulk
      sediment toxicant concentration, the most widely used chemical parameter, does
      not always represent the bioavailable concentration, particularly for hydrophobic
      organic compounds (HOCs) in highly contaminated sediments. In the present study,
      we developed and tested a pore-water sampler that uses solid-phase
      microextraction (SPME) to measure freely dissolved (bioavailable) HOC
      concentrations. A single polydimethylsiloxane (PDMS)-coated SPME fiber is secured
      in a compact, protective housing that allows aqueous exchange with whole sediment
      while eliminating direct contact with sediment particles. Fibers with three PDMS
      coating thicknesses were first calibrated for 12 model HOCs of current regulatory
      concern. Precalibrated samplers were exposed to spiked estuarine sediment in
      laboratory microcosms to determine the time to equilibrium and the equilibrium
      concentrations across a range of sediment contamination. Time to equilibrium
      ranged from 14 to 110 d, with 30 d being sufficient for more than half the target
      HOCs. Equilibrium SPME measurements, ranging from 0.009 to 2,400 ng/L, were
      highly correlated with but, in general, lower than HOC pore-water concentrations
      determined independently by liquid-liquid extraction. This concept shows promise
      for directly measuring the freely dissolved concentration of HOCs in sediment
      pore water, a previously difficult-to-measure parameter that will improve our
      ability to assess the impacts of contaminated sediments.

PMID- 19391691
TI  - Long-range transport of organic chemicals in the environment.
AB  - The long-range transport (LRT) of organic chemicals in the environment is
      reviewed, with particular focus on the role of environmental fate and transport
      models and the relationship between model results and field data. Results from
      generic multimedia box models, spatially resolved multimedia box models, and
      atmospheric transport models are highlighted, including conceptual investigations
      of cold-trap effect and global fractionation as well as results for particular
      chemicals, such as hexachlorocyclohexanes, DDT, polychlorinated biphenyls,
      perfluoroocctanoic acid, and polybrominated diphenyl ethers. Comparison of model
      results to field data shows that in many cases environmental fate models provide
      a good description of the distribution dynamics observed in the field, with
      deviations between measured and modeled concentrations around a factor of five.
      Sorption to atmospheric aerosols as a key process influencing the LRT of
      semivolatile organic chemicals (SOCs) is discussed, and the need for more
      measurements of the aerosol-air partitioning of SOCs and of the reactivity of
      particle-bound chemicals is pointed out. Key findings from field campaigns
      measuring legacy persistent organic pollutants (POPs) as well as new POPs are
      summarized. Finally, the relationship between science and politics in the field
      of POPs is addressed. Research into the LRT of organic chemicals has always
      occurred in interaction with political activities aiming to reduce the emissions
      of POPs. Since the late 1990s, the Stockholm Convention and the Aarhus Protocol
      on POPs have formed an important political context for research concerning POPs;
      the implementation of these international treaties creates a demand for ongoing
      research into the LRT of organic chemicals.

PMID- 19391692
TI  - Effect of competing ions and complexing organic substances on the cadmium uptake
      by the soil bacterium Sinorhizobium meliloti.
AB  - In an effort to improve the understanding and prediction of Cd uptake by soil
      bacteria, adsorbed and intracellular Cd were determined in unpolluted and highly
      polluted model soil solutions within a concentration range spanning from 10(-9)
      to 5 x 10(-5) M Cd. In parallel, the free Cd ion concentrations ([Cd(2+)]) were
      measured by a hollow fiber permeation liquid membrane. Obtained results
      demonstrated that Cd uptake by bacterium Sinorhizobium meliloti was related to
      [Cd(2+)] in the solution. Addition of different complexing organic substances
      reduced [Cd(2+)] in the bacterial medium and decreased both adsorbed and
      intracellular Cd. The adsorbed Cd was considerably reduced in the presence of 10(
      4) to 5 x 10(-2) M [Ca] or [Mg]. No effect on Cd adsorption was observed in the
      presence of Zn or Mn, even at 100-fold excess. Intracellular Cd decreased in the
      presence of a high excess of Ca and Zn, while no significant effect was observed
      in the presence of Mg. An increase of dissolved Mn from 10(-9) to 10(-8) M
      resulted in a twofold decrease of the intracellular Cd, but no clear trend was
      observed in the presence of 10(-7) to 10(-6) M Mn. Based on complexation and
      competition studies, the stability constants, necessary for quantitative
      description of Cd uptake by S. meliloti and the development of the bacterial
      biotic ligand model for Cd, were derived and validated in the solutions
      containing mixtures of Cd, Zn, Ca, and Mg. Further numerical simulations of Cd
      uptake by S. meliloti exposed to soil pore waters demonstrated the importance of
      Zn competition and the insignificant influence of Ca and H on Cd uptake.

PMID- 19391693
TI  - Density-matrix renormalization-group study of current and activity fluctuations
      near nonequilibrium phase transitions.
AB  - Cumulants of a fluctuating current can be obtained from a free-energy-like
      generating function, which for Markov processes equals the largest eigenvalue of
      a generalized generator. We determine this eigenvalue with the density-matrix
      renormalization group for stochastic systems. We calculate the variance of the
      current in the different phases, and at the phase transitions, of the totally
      asymmetric exclusion process. Our results can be described in the terms of a
      scaling ansatz that involves the dynamical exponent z . We also calculate the
      generating function of the dynamical activity (total number of configuration
      changes) near the absorbing-state transition of the contact process. Its scaling
      properties can be expressed in terms of known critical exponents.

PMID- 19391694
TI  - Universal condition for critical percolation thresholds of kagome-like lattices.
AB  - Lattices that can be represented in a kagome-like form are shown to satisfy a
      universal percolation criticality condition, expressed as a relation between P3 ,
      the probability that all three vertices in the triangle connect, and P0 , the
      probability that none connect. A linear approximation for P3(P0) is derived and
      appears to provide a rigorous upper bound for critical thresholds. A numerically
      determined relation for P3(P0) gives thresholds for the kagome, site-bond
      honeycomb, (3-12;{2}) lattice, and "stack-of-triangle" lattices that compare
      favorably with numerical results.

PMID- 19391695
TI  - Ground-state entropy of the random vertex-cover problem.
AB  - Counting the number of ground states for a spin-glass or nondeterministic
      polynomial-complete combinatorial optimization problem is even more difficult
      than the already hard task of finding a single ground state. In this paper the
      entropy of minimum vertex covers of random graphs is estimated through a set of
      iterative equations based on the cavity method of statistical mechanics. During
      the iteration both the cavity entropy contributions and cavity magnetizations for
      each vertex are updated. This approach overcomes the difficulty of iterative
      divergence encountered in the zero-temperature first-step replica-symmetry
      breaking (1RSB) spin-glass theory. It is still applicable when the 1RSB mean
      field theory is no longer stable. The method can be extended to compute the
      entropies of ground states and metastable minimal-energy states for other random
      graph spin-glass systems.

PMID- 19391696
TI  - Optimal percolation of disordered segregated composites.
AB  - We evaluate the percolation threshold values for a realistic model of continuum
      segregated systems, where random spherical inclusions forbid the percolating
      objects, modeled by hardcore spherical particles surrounded by penetrable shells,
      to occupy large regions inside the composite. We find that the percolation
      threshold is generally a nonmonotonous function of segregation, and that an
      optimal (i.e., minimum) critical concentration exists well before maximum
      segregation is reached. We interpret this feature as originating from a
      competition between reduced available volume effects and enhanced concentrations
      needed to ensure percolation in the highly segregated regime. The relevance with
      existing segregated materials is discussed.

PMID- 19391697
TI  - Method for computing short-range forces between solid-liquid interfaces driving
      grain boundary premelting.
AB  - We present a molecular dynamics based method for accurately computing short-range
      structural forces resulting from the overlap of spatially diffuse solid-liquid
      interfaces at wetted grain boundaries close to the melting point. The method is
      based on monitoring the fluctuations of the liquid layer width at different
      temperatures to extract the excess interfacial free energy as a function of this
      width. The method is illustrated for a high-energy Sigma9 twist boundary in pure
      Ni. The short-range repulsion driving premelting is found to be dominant in
      comparison to long-range dispersion and entropic forces and consistent with
      previous experimental findings that nanometer-scale layer widths may be observed
      only very close to the melting point.

PMID- 19391698
TI  - Parameters influencing diffusion dynamics of an adsorbed polymer chain.
AB  - Brownian dynamics simulations with hydrodynamic interaction (HI) are performed to
      study the effect of chain length on the diffusion of a polymer chain adsorbed
      onto flat surfaces. Bead-rod as well as bead-spring chains, with Hookean and
      finitely extensible nonlinear elastic (FENE) springs, are used to model the
      polymer chain, and the no-slip boundary condition for the solvent is incorporated
      exactly. Simulations for short chains (N<or=100) predict that the translational
      diffusivity in the planar direction D{ parallel} approximately N;{-nu} , where N
      is the chain length, with nu approximately 0.75 for bead-rod chains and bead
      spring chains connected by stiff FENE springs and nu approximately 1 for bead
      spring chains connected by flexible FENE and Hookean springs. We find that near
      chemically homogeneous surfaces, the scaling exponent nu depends upon three
      factors: chain flexibility, strength of HI, and solvent quality. The nu value
      changes from 0.75 to 1 with either an increase in chain flexibility, a decrease
      in the strength of HI, or a decrease in solvent quality. However, near a
      chemically heterogeneous surface, nu is always 1.

PMID- 19391699
TI  - Residue network in protein native structure belongs to the universality class of
      a three-dimensional critical percolation cluster.
AB  - Single protein molecules are regarded as contact networks of amino-acid residues.
      Relationships between the shortest path lengths and the numbers of residues
      within single molecules in the native structures are examined for various sized
      proteins. A universal scaling among proteins is obtained, which shows that the
      residue networks are fractal networks. This universal fractal network is
      characterized with three kinds of dimensions: the network topological dimension
      D{c} approximately 1.9 , the fractal dimension D{f} approximately 2.5 , and the
      spectral dimension D{s} approximately 1.3 . These values are in surprisingly good
      coincidence with those of the three-dimensional critical percolation cluster.
      Hence the residue contact networks in the protein native structures belong to the
      universality class of the three-dimensional percolation cluster. The criticality
      is relevant to the ambivalence in the protein native structures, the coexistence
      of stability and instability, both of which are necessary for protein functions.

PMID- 19391700
TI  - Relaxation dynamics near nonequilibrium stationary states in Brownian ratchets.
AB  - A comprehensive study of the static and dynamical properties of a representative
      stochastic model of Brownian ratchet effects for molecular motors is reported.
      The model describes Brownian motions on two periodic potentials under static and
      time-dependent forces, where there are two distinct locations of chemical
      reactions coupling the levels with reversible rates within a period. Complete
      stationary properties have been obtained analytically for arbitrary potentials
      under external force. Dynamical relaxation properties near nonequilibrium
      stationary states were examined by considering the response function of velocity
      upon time-dependent external force, expressed in terms of the conditional
      probability density of the model. The latter is fully calculated using a
      systematic numerical method using matrix diagonalization, which is easily
      generalized to more complicated models for studying both static and dynamical
      properties. The behavior of the time-dependent response examined for model
      potentials suggests that the characteristic relaxation time near stationary
      states generally decreases linearly with respect to increasing velocity as one
      goes away from equilibrium via an increase in chemical potential of fuel species,
      a prediction testable in single molecule experiments.

PMID- 19391701
TI  - Packing a multidisperse system of hard disks in a circular environment.
AB  - We consider the problem of finding the densest closed packing of hard disks with
      proposed different radii in a circular environment, such that the radius of the
      circumcircle is minimal. With our approach, we are able to find denser packings
      for various problem instances than known from the literature. Both for the
      dynamics of the simulation and for the optimum values of the radii of the
      circumcircles, we find various scaling laws.

PMID- 19391702
TI  - Additional constraints in adsorption-desorption kinetics.
AB  - In this work, the adsorption-desorption kinetic in the framework of the lattice
      gas model is analyzed. The transition probabilities are written as an expansion
      of the occupation configurations. Due to that, the detail balance principle
      determine half of the adsorption A{i} and desorption D{i} coefficients,
      consequently, different functional relations between them are proposed.
      Introducing additional constrains, it is demonstrated that when those
      coefficients are linearly related through a parameter gamma , there are values of
      lateral interaction V , that lead to anomalous behavior in the adsorption
      isotherms, the sticking coefficient and the thermal programmed desorption
      spectra. Diagrams for the allowed values of V and gamma are also shown.
      Alternatively, a more reliable formulation for the adsorption desorption kinetic
      based on the transition state theory is introduced. In such way the equilibrium
      and non equilibrium observables do not present anomalous or inconsistent
      behavior.

PMID- 19391703
TI  - Quantum Monte Carlo method for the Bose-Hubbard model with harmonic confining
      potential.
AB  - We study the Bose-Hubbard model with an external harmonic field, which is
      effective for modeling a cold atomic Bose gas trapped in an optical lattice. We
      modify the directed-loop algorithm to simulate large systems efficiently. As a
      demonstration we carry out the simulation of a system consisting of 1. 8 x 10{5}
      particles on a 64{3} lattice. These numbers are comparable to those in the
      pioneering experimental work by Greiner [Nature (London) 415, 39 (2002)].
      Furthermore, we observe coherence between two superfluid spheres separated by a
      Mott insulator region in a "wedding-cake" structure.

PMID- 19391704
TI  - Pressure-induced orientational glass phase in molecular para-hydrogen.
AB  - We propose a theoretical description of a possible orientational glass transition
      in solid molecular para-hydrogen and ortho-deuterium under pressure supposing
      that they are mixtures of J=0 and J=2 states of molecules. The theory uses the
      basic concepts and methods of standard spin-glass theory. We expect our
      orientational glass to correspond to the II' phase of the high-pressure hydrogen
      phase diagram.

PMID- 19391705
TI  - Illustrative example of the relationship between dissipation and relative
      entropy.
AB  - Kawai, Parrondo, and Van den Broeck [Phys. Rev. Lett. 98, 080602 (2007)] have
      recently established a quantitative relationship between dissipated work and a
      microscopic, information-theoretic measure of irreversibility. We illustrate this
      result using the exactly solvable system of a Brownian particle in a dragged
      harmonic trap.

PMID- 19391706
TI  - Logarithmic correction to scaling in domain-wall dynamics at Kosterlitz-Thouless
      phase transitions.
AB  - With Monte Carlo simulations, we investigate the relaxation dynamics of domain
      walls at the Kosterlitz-Thouless phase transition, taking the two-dimensional XY
      model as an example. The dynamic scaling behavior is carefully analyzed, and a
      domain-wall roughening process is observed. Two-time correlation functions are
      calculated and aging phenomena are investigated. Inside the domain interface, a
      strong logarithmic correction to scaling is detected.

PMID- 19391707
TI  - Rotary motors sliding along surfaces.
AB  - We introduce a family of molecular rotors that may convert light or chemical
      energy into directed translational motion along surfaces. The dependencies of
      diffusion coefficient and drift velocity of the rotating molecule on the
      magnitude of external torque, symmetry of surface potential, and temperature have
      been investigated. Our simulations show that the rotation-translation coupling
      could be very effective, and the molecule may move by approximately one surface
      lattice spacing per complete rotation. We have found that the unidirectionality
      of the rotary motion is not required to produce efficient directed sliding; this
      effect can be achieved by applying a time-periodic, or even randomly, oscillating
      torque which induces alternating molecular reorientations but does not generate
      complete rotations.

PMID- 19391708
TI  - Statistical properties of the final state in one-dimensional ballistic
      aggregation.
AB  - We investigate the long time behavior of the one-dimensional ballistic
      aggregation model that represents a sticky gas of N particles with random initial
      positions and velocities, moving deterministically, and forming aggregates when
      they collide. We obtain a closed formula for the stationary measure of the system
      which allows us to analyze some remarkable features of the final "fan" state. In
      particular, we identify universal properties which are independent of the initial
      position and velocity distributions of the particles. We study cluster
      distributions and derive exact results for extreme value statistics (because of
      correlations these distributions do not belong to the Gumbel-Frechet-Weibull
      universality classes). We also derive the energy distribution in the final state.
      This model generates dynamically many different scales and can be viewed as one
      of the simplest exactly solvable model of N -body dissipative dynamics.

PMID- 19391709
TI  - Quenched-vacancy induced spin-glass order.
AB  - The ferromagnetic phase of an Ising model in d=3 , with any amount of quenched
      antiferromagnetic bond randomness, is shown to undergo a transition to a spin
      glass phase under sufficient quenched bond dilution. This result, demonstrated
      here with the numerically exact global renormalization-group solution of a d=3
      hierarchical lattice, is expected to hold true generally, for the cubic lattice
      and for quenched site dilution. Conversely, in the ferromagnetic-spin-glass
      antiferromagnetic phase diagram, the spin-glass phase expands under quenched
      dilution at the expense of the ferromagnetic and antiferromagnetic phases. In the
      ferromagnetic-spin-glass phase transition induced by quenched dilution,
      reentrance as a function of temperature is seen, as previously found in the
      ferromagnetic-spin-glass transition induced by increasing the antiferromagnetic
      bond concentration.

PMID- 19391710
TI  - Equilibrium long-ranged charge correlations at the surface of a conductor coupled
      to electromagnetic radiation. II.
AB  - Results of a previous paper with the same title are retrieved by a different
      method. A one-component plasma is bounded by a plane surface. The plasma is fully
      coupled to the electromagnetic field, therefore, the charge correlations are
      retarded. The quantum correlation function of the surface charge densities, at
      times different by t , at asymptotical large distances R, at inverse temperature
      beta , decays as -1(8pi{2}betaR{3}) , a surprisingly simple result: The decay is
      independent of Planck's constant variant Planck's over 2pi , the time difference
      t , and the velocity of light c. The present paper is based on the analysis of
      the collective vibration modes of the system.

PMID- 19391711
TI  - Currents in nonequilibrium statistical mechanics.
AB  - Nonzero currents characterize the nonequilibrium state in stochastic dynamics (or
      master equation) models of natural systems. In such models there is a matrix R of
      transition probabilities connecting the states of the system. We show that if the
      strength of a transition increases, so does the current along the corresponding
      bond. We also address the inverse problem: given a set of observed currents, we
      show the extent to which the original " R " can be recovered. These
      considerations lead to a general discussion of time scales and substance flows.

PMID- 19391712
TI  - Delocalization transition of a small number of particles in a box with periodic
      boundary conditions.
AB  - We perform molecular dynamics simulation of a small number of particles in a box
      with periodic boundary conditions from a viewpoint of chaotic dynamical systems.
      There is a transition at a critical energy E{c} that each particle is confined in
      each unit cell for E<E{c}, and the chaotic diffusion occurs for E>E{c}. We find
      an anomalous behavior of the jump frequency above the critical energy in a two
      particle system, which is related with the infinitely alternating stability
      change of the straight motion passing through a saddle point. We find
      simultaneous jump motions just above the critical energy in a four-particle
      system and 16-particle system, which is also related with the motion passing
      through the saddle point.

PMID- 19391713
TI  - Unification of hierarchical reference theory and self-consistent Ornstein-Zernike
      approximation: analysis of the critical region for fluids and lattice gases.
AB  - The hierarchical reference theory (HRT) and the self-consistent Ornstein-Zernike
      approximation (SCOZA) are two liquid state theories that both yield a largely
      satisfactory description of the critical region as well as the phase coexistence
      and equation of state in general. In two previous works, unification of these
      theories has been considered and general equations were established. Further it
      was shown that the solution of the mean spherical model and a generalized version
      of it can be obtained in this way. In the present work, analysis of the critical
      region for fluids and lattice gases is performed. A key result of our HRT-SCOZA
      approximation is that for the standard three-dimensional fluid, lattice gas, or
      Ising model, the critical index for the critical isotherm is delta=5 and for the
      curve of coexistence it is beta=13 provided full scaling is assumed. More
      generally we find beta=2(delta+1) .

PMID- 19391714
TI  - From Ornstein-Uhlenbeck dynamics to long-memory processes and fractional Brownian
      motion.
AB  - This article establishes a natural physical path leading from "regular" Ornstein
      Uhlenbeck dynamics to "anomalous" long-memory processes and, thereafter, to
      fractional Brownian motion. Considering a system composed of n different parts
      each part conducting its own Ornstein-Uhlenbeck dynamics, and all parts being
      perturbed by a common external Levy noise-we show that the collective system
      dynamics, in the limit n-->infinity , converges to a temporal moving-average of
      the driving noise. The limiting moving-average process, in turn, can possess a
      long memory-in which case, when observed over large time scales, further yields
      fractional Brownian motion. The temporal correlation structure of the limiting
      moving-average process turns out to be determined by the structural statistical
      variability of the system's composing parts. Thus, the emergence of a long memory
      is a consequence of the intrinsic "quenched disorder" present at the system's
      formation epoch rather than the consequence of the external annealed disorder
      carried in continuously by the driving noise.

PMID- 19391715
TI  - General two-order-parameter Ginzburg-Landau model with quadratic and quartic
      interactions.
AB  - The Ginzburg-Landau model with two-order parameters appears in many condensed
      matter problems. However, even for scalar order parameters, the most general U(1)
      symmetric Landau potential with all quadratic and quartic terms contains 13
      independent coefficients and cannot be minimized with straightforward algebra.
      Here, we develop a geometric approach that circumvents this computational
      difficulty and allows one to study properties of the model without knowing the
      exact position of the minimum. In particular, we find the number of minima of the
      potential, classify explicit symmetries possible in this model, establish
      conditions when and how these symmetries are spontaneously broken, and explicitly
      describe the phase diagram.

PMID- 19391716
TI  - Death of an A -particle island in the B -particle sea: propagation and evolution
      of the reaction front A+B<-->C.
AB  - We present a systematic theory of propagation and evolution of the reaction front
      A+B<-->C in the reaction-diffusion system where an island of particles A is
      surrounded by the uniform sea of particles B . In the first part of the work we
      give a systematic analysis of the crossover from the irreversible to reversible
      regime of front propagation in terms of the quasistatic approximation (QSA) and
      derive the key condition for the island death in the quasiequilibrium front
      regime. We show that the same as in the case of pure annihilation A+B-->0 the QSA
      enables the description of the quasiequilibrium front propagation only to a
      critical point t{c} on approaching to which the QSA is violated. In the second
      part of the work under the assumption of a sufficiently large forward reaction
      constant k we derive the perturbative expansion in powers of 1k which gives the
      asymptotically exact description of the quasiequilibrium front evolution up to t-
      >infinity. We demonstrate that below some critical value of the reduced backward
      reaction constant g<g{c} there appear two turning points on the front trajectory,
      the first of which arises at the sharp localized front stage and is due to the
      finite number of island particles whereas the second is a consequence of radical
      transformation of the front structure at the passage through the critical point
      (delocalization of the front). We find a remarkable property of self-similarity
      of the passage through the critical point, we derive scaling laws for such
      passage and show that in the limit g-->0 these laws lead to a striking phenomenon
      of an abrupt delocalization of the front.

PMID- 19391717
TI  - Percolation in networks with voids and bottlenecks.
AB  - A general method is proposed for predicting the asymptotic percolation threshold
      of networks with bottlenecks, in the limit that the subnet mesh size goes to
      zero. The validity of this method is tested for bond percolation on filled
      checkerboard and "stack-of-triangle" lattices. Thresholds for the checkerboard
      lattices of different mesh sizes are estimated using the gradient percolation
      method, while for the triangular system they are found exactly using the triangle
      triangle transformation. The values of the thresholds approach the asymptotic
      values of 0.64222 and 0.53993, respectively, as the mesh is made finer,
      consistent with a direct determination based upon the predicted critical corner
      connection probability.

PMID- 19391718
TI  - Generalized fluctuation-dissipation and reciprocal relations for Brownian sieves
      and molecular machines.
AB  - A Brownian sieve is a spatially periodic microstructured device that combines the
      effects of thermal noise, local spatial asymmetry, and external forces to
      separate particles based on their transport properties. By treating the motion of
      an individual particle as a cyclical process in which the particle fluctuates
      away from and returns to the origin of some unit cell, I derive generalized
      fluctuation-dissipation and reciprocal relations for the averages (and for all
      moments) of the number of periodic displacements that are exact and valid for
      arbitrary values of the external forces. These relations hold not only for
      Brownian sieves, but for all molecular machines in which a nanoscale system
      couples two chemical, mechanical, or transport processes by a cycle in which the
      molecular machine itself fluctuates away from and then returns to some arbitrary
      reference state, in the process doing or receiving work on or from the
      environment.

PMID- 19391719
TI  - Canonical active Brownian motion.
AB  - Active Brownian motion is the complex motion of active Brownian particles. They
      are "active" in the sense that they can transform their internal energy into
      energy of motion and thus create complex motion patterns. Theories of active
      Brownian motion so far imposed couplings between the internal energy and the
      kinetic energy of the system. We investigate how this idea can be naturally taken
      further to include also couplings to the potential energy, which finally leads to
      a general theory of canonical dissipative systems. Explicit analytical and
      numerical studies are done for the motion of one particle in harmonic external
      potentials. Apart from stationary solutions, we study nonequilibrium dynamics and
      show the existence of various bifurcation phenomena.

PMID- 19391720
TI  - Statistics of trajectories in two-state master equations.
AB  - We derive a simple expression for the probability of trajectories of a master
      equation. The expression is particularly useful when the number of states is
      small and permits the calculation of observables that can be defined as
      functionals of whole trajectories. We illustrate the method with a two-state
      master equation, for which we calculate the distribution of the time spent in one
      state and the distribution of the number of transitions, each in a given time
      interval. These two expressions are obtained analytically in terms of modified
      Bessel functions.

PMID- 19391721
TI  - Path integral analysis of Jarzynski's equality: analytical results.
AB  - We apply path integrals to study nonequilibrium work theorems in the context of
      Brownian dynamics, deriving in particular the equations of motion governing the
      most typical and most dominant trajectories. For the analytically soluble cases
      of a moving harmonic potential and a harmonic oscillator with a time-dependent
      natural frequency, we find such trajectories, evaluate the work-weighted
      propagators, and validate Jarzynski's equality.

PMID- 19391722
TI  - Work distributions in the T=0 random field Ising model.
AB  - We perform a numerical study of the three-dimensional random-field Ising model at
      T=0. We compare work distributions along metastable trajectories obtained with
      the single-spin flip dynamics with the distribution of the internal energy change
      along equilibrium trajectories. The goal is to investigate the possibility of
      extending the Crooks fluctuation theorem [G. E. Crooks, Phys. Rev. E. 60, 2721
      (1999)] to zero temperature when, instead of the standard ensemble statistics,
      one considers the ensemble generated by the quenched disorder. We show that a
      simple extension of Crooks fails close to the disordered induced equilibrium
      phase transition due to the fact that work and internal energy distributions are
      very asymmetric.

PMID- 19391723
TI  - Dynamic renormalization in the framework of nonequilibrium thermodynamics.
AB  - We show how the dynamic renormalization of nonequilibrium systems can be carried
      out within the general framework of nonequilibrium thermodynamics. Whereas the
      renormalization of Hamiltonians is well known from equilibrium thermodynamics,
      the renormalization of dissipative brackets, or friction matrices, is the main
      new feature for nonequilibrium systems. Renormalization is a reduction rather
      than a coarse-graining technique; that is, no new dissipative processes arise in
      the dynamic renormalization procedure. The general ideas are illustrated for
      dilute polymer solutions where, in renormalizing bead-spring chain models,
      dissipative hydrodynamic interactions between different smaller beads contribute
      to the friction coefficient of a single larger bead.

PMID- 19391724
TI  - Mapping of (2+1) -dimensional Kardar-Parisi-Zhang growth onto a driven lattice
      gas model of dimers.
AB  - We show that a (2+1) -dimensional discrete surface growth model exhibiting Kardar
      Parisi-Zhang (KPZ) class scaling can be mapped onto a two-dimensional conserved
      lattice gas model of directed dimers. The KPZ height anisotropy in the surface
      model corresponds to a driven diffusive motion of the lattice gas dimers. We
      confirm by numerical simulations that the scaling exponents of the dimer model
      are in agreement with those of the (2+1) -dimensional KPZ class. This opens up
      the possibility of analyzing growth models via reaction-diffusion models, which
      allow much more efficient computer simulations.

PMID- 19391725
TI  - Hopping transport in hostile reaction-diffusion systems.
AB  - We investigate transport in a disordered reaction-diffusion model consisting of
      particles which are allowed to diffuse, compete with one another (2A-->A) , give
      birth in small areas called "oases" (A-->2A) , and die in the "desert" outside
      the oases (A-->0) . This model has previously been used to study bacterial
      populations in the laboratory and is related to a model of plankton populations
      in the oceans. We first consider the nature of transport between two oases: In
      the limit of high growth rate, this is effectively a first passage process, and
      we are able to determine the first passage time probability density function in
      the limit of large oasis separation. This result is then used along with the
      theory of hopping conduction in doped semiconductors to estimate the time taken
      by a population to cross a large system.

PMID- 19391726
TI  - Exact solution for mean first-passage time on a pseudofractal scale-free web.
AB  - The explicit determinations of the mean first-passage time (MFPT) for trapping
      problem are limited to some simple structure, e.g., regular lattices and regular
      geometrical fractals, and determining MFPT for random walks on other media,
      especially complex real networks, is a theoretical challenge. In this paper, we
      investigate a simple random walk on the the pseudofractal scale-free web (PSFW)
      with a perfect trap located at a node with the highest degree, which
      simultaneously exhibits the remarkable scale-free and small-world properties
      observed in real networks. We obtain the exact solution for the MFPT that is
      calculated through the recurrence relations derived from the structure of PSFW.
      The rigorous solution exhibits that the MFPT approximately increases as a power
      law function of the number of nodes, with the exponent less than 1. We confirm
      the closed-form solution by direct numerical calculations. We show that the
      structure of PSFW can improve the efficiency of transport by diffusion, compared
      with some other structure, such as regular lattices, Sierpinski fractals, and T
      graph. The analytical method can be applied to other deterministic networks,
      making the accurate computation of MFPT possible.

PMID- 19391727
TI  - Relativistic diffusion.
AB  - We discuss relativistic diffusion in proper time in the approach of Schay (Ph.D.
      thesis, Princeton University, Princeton, NJ, 1961) and Dudley [Ark. Mat. 6, 241
      (1965)]. We derive (Langevin) stochastic differential equations in various
      coordinates. We show that in some coordinates the stochastic differential
      equations become linear. We obtain momentum probability distribution in an
      explicit form. We discuss a relativistic particle diffusing in an external
      electromagnetic field. We solve the Langevin equations in the case of parallel
      electric and magnetic fields. We derive a kinetic equation for the evolution of
      the probability distribution. We discuss drag terms leading to an equilibrium
      distribution. The relativistic analog of the Ornstein-Uhlenbeck process is not
      unique. We show that if the drag comes from a diffusion approximation to the
      master equation then its form is strongly restricted. The drag leading to the
      Tsallis equilibrium distribution satisfies this restriction whereas the one of
      the Juttner distribution does not. We show that any function of the relativistic
      energy can be the equilibrium distribution for a particle in a static electric
      field. A preliminary study of the time evolution with friction is presented. It
      is shown that the problem is equivalent to quantum mechanics of a particle moving
      on a hyperboloid with a potential determined by the drag. A relation to
      diffusions appearing in heavy ion collisions is briefly discussed.

PMID- 19391728
TI  - Locations of multicritical points for spin glasses on regular lattices.
AB  - We present an analysis leading to precise locations of the multicritical points
      for spin glasses on regular lattices. The conventional technique for
      determination of the location of the multicritical point was previously derived
      using a hypothesis emerging from duality and the replica method. In the present
      study, we propose a systematic technique, by an improved technique, giving more
      precise locations of the multicritical points on the square, triangular, and
      hexagonal lattices by carefully examining the relationship between two partition
      functions related with each other by the duality. We can find that the
      multicritical points of the +/-J Ising model are located at p{c}=0.890813 on the
      square lattice, where p{c} means the probability of J{ij}=J(>0) , at
      p{c}=0.835985 on the triangular lattice, and at p{c}=0.932593 on the hexagonal
      lattice. These results are in excellent agreement with recent numerical
      estimations.

PMID- 19391729
TI  - Low-temperature thermodynamics in the context of dissipative diamagnetism.
AB  - We revisit here the effect of quantum dissipation on the much studied problem of
      Landau diamagnetism and analyze the results in the light of the third law of
      thermodynamics. The case of an additional parabolic potential is separately
      assessed. We find that dissipation arising from strong coupling of the system to
      its environment qualitatively alters the low-temperature thermodynamic attributes
      such as the entropy and the specific heat.

PMID- 19391730
TI  - Shear viscosity of the Lennard-Jones chain fluid in its gaseous, supercritical,
      and liquid states.
AB  - Extensive nonequilibrium molecular dynamics (NEMD) simulations have been carried
      out in order to estimate the Newtonian shear viscosity of a fluid composed of
      short chains (up to 16 segments) of jointed spheres [Lennard-Jones chain (LJC)]
      over a large range of thermodynamic conditions. Using the NEMD results, it is
      shown that the zero-density contribution decreases with the chain length for a
      given temperature and is simply proportional to N-1/2 , where N is the number of
      spheres composing the chain. In addition, it has been noticed that the residual
      shear viscosity is proportional to the chain length. Then, using these results, a
      relation is proposed to correlate the shear viscosity of the LJC fluid using the
      LJ fluid (the monomer) as a reference. It is shown that this correlation is able
      to provide an excellent estimation of the LJC fluid viscosity compared to NEMD
      results for N<or=16 over the domain 0<or=rho <or=1.1 and 0.7<or=T <or=6 .
      Finally, it is shown that the LJC model is unambiguously more efficient than a
      simple LJ approximation when applied to estimate the shear viscosity of n 
      butane, if only the sphere or segment diameter is used as an adjustable parameter
      in both models.

PMID- 19391731
TI  - Effect of pore structure on capillary condensation in a porous medium.
AB  - The Kelvin equation relates the equilibrium vapor pressure of a fluid to the
      curvature of the fluid-vapor interface and predicts that vapor condensation will
      occur in pores or irregularities that are sufficiently small. Past analyses of
      capillary condensation in porous systems with fractal structure have related the
      phenomenon to the fractal dimension of the pore volume distribution. Recent work,
      however, suggests that porous systems can exhibit distinct fractal dimensions
      that are characteristic of both their pore volume and the surfaces of the pores
      themselves. We show that both fractal dimensions have an effect on the
      thermodynamics that governs capillary condensation and that previous analyses can
      be obtained as limiting cases of a more general formulation.

PMID- 19391732
TI  - Nonequilibrium mode-coupling theory for uniformly sheared systems.
AB  - We develop a nonequilibrium mode-coupling theory for uniformly sheared systems
      starting from microscopic, thermostatted Sllod equations of motion. Our theory
      aims at describing stationary-state properties including rheological ones of
      sheared systems, and this is accomplished via two steps. First, a set of self
      consistent equations is formulated based on the projection-operator formalism and
      on the mode-coupling approach for the transient density correlators which measure
      the correlations between the density fluctuations in the initial equilibrium
      state and the ones at later times after the shearing force is turned on. The
      transient time-correlation function formalism is then used which, combined with
      the mode-coupling approximation, expresses stationary-state properties in terms
      of the transient density correlators. A detailed comparison of our theory is also
      presented with the related mode-coupling theory which is based on the
      Smoluchowski equation for Brownian particles under stationary shearing.

PMID- 19391733
TI  - Dynamics of crater formations in immersed granular materials.
AB  - We report the formation of a crater at the free surface of an immersed granular
      bed, locally crossed by an ascending gas flow. In two dimensions, the crater
      consists of two piles which develop around the location of the gas emission. We
      observe that the typical size of the crater increases logarithmically with time,
      independently of the gas emission dynamics. We describe the related granular
      flows and give an account of the influence of the experimental parameters,
      especially of the grain size and of the gas flow.

PMID- 19391734
TI  - Chain formation of spheres in oscillatory fluid flows.
AB  - A collection of spherical particles subjected to horizontal oscillatory fluid
      flow is known to form chains perpendicular to the direction of the oscillation.
      We have developed computer simulations to model such a system and have validated
      them against experiments carried out in a small fluid-filled cell. In both
      experiment and simulation we find that the particles go through the same stages
      of evolution from a dispersed initial configuration to an ordered chain
      structure. We then use our computer simulations to investigate in detail the
      interactions responsible for chain formation and the interaction between fully
      formed chains.

PMID- 19391735
TI  - Equivalence of the freely cooling granular gas to the sticky gas.
AB  - A freely cooling granular gas with a velocity-dependent restitution coefficient
      is studied in one dimension. The restitution coefficient becomes near elastic
      when the relative velocity of the colliding particles is less than a velocity
      scale delta . Different statistical quantities, namely, density distribution,
      occupied and empty cluster length distributions, and spatial density and velocity
      correlation functions, are obtained using event driven molecular dynamic
      simulations. We compare these with the corresponding quantities of the sticky gas
      (inelastic gas with zero coefficient of restitution). We find that in the
      inhomogeneous cooling regime, for times smaller than a crossover time t{1} ,
      where t{1} approximately delta;{-1} , the behavior of the granular gas is
      equivalent to that of the sticky gas. When delta-->0 , then t{1}-->infinity and,
      hence, the results support an earlier claim that the freely cooling inelastic gas
      is described by the inviscid Burgers equation. For a real granular gas with
      finite delta , the existence of the time scale t{1} shows that, for large times,
      the granular gas is not described by the inviscid Burgers equation.

PMID- 19391736
TI  - Characterization of clusters in rapid granular flows.
AB  - The clustering phenomenon within two-dimensional, rapid granular, simple shear
      flows is investigated. Two characterizations are developed and implemented for
      monodisperse systems, revealing physically meaningful insight. First, a new
      feature of the radial distribution function is identified for these dissipative
      granular systems, which is not present in molecular (nondissipative) systems.
      Namely, a long-scale minimum occurs at a distance representing the average
      distance between the center of a cluster and the center of a dilute region.
      Results indicate that center-to-center distances are least (i.e., clusters are
      most tightly packed) for systems of moderate particle concentrations and low
      restitution coefficients. In addition, concentration and temperature measurements
      of clustered and dilute regions are also obtained using a Gaussian filter that is
      based on this center-to-center distance and, thus, provides a means of
      appropriately defining local concentrations. These results confirm previous
      findings that cluster prevalence increases with decreasing dissipation and that
      clustered regions have lower temperatures than their dilute counterparts.
      Surprisingly, however, the results indicate that cluster prevalence, defined by
      normalized concentration differences between the two regions, decrease
      monotonically with an increase in overall particle concentration.

PMID- 19391737
TI  - Three-dimensional analysis of the collision process of a bead on a granular
      packing.
AB  - We present results of the collision process of a bead onto a static granular
      packing. We provide, in particular, a three-dimensional (3D) extensive
      characterization of this process from a model experiment that allows us to propel
      a spherical bead onto a granular packing with a well-controlled velocity and
      impact angle. A collision typically produces a high-energy particle (rebound
      particle) and several low-energy grains (ejected particles). The collision
      process is recorded by means of two fast video cameras. The sequence of images
      from both cameras are then analyzed via image processing and the trajectories of
      all particles are reconstructed in 3D space. We show that the incident particle
      does not remain in the vertical incident plane after the rebound and that the
      deviation angle increases with increasing impact angle. Concerning the ejected
      particles, we demonstrated that the ejection angle (measured with respect to the
      horizontal plane) is surprisingly independent of both the impact angle and
      velocity of the incident particle, and is very close to 60 degrees . The
      horizontal component of the ejection speed of the splashed particles is found to
      be weakly dependent on the incident speed and impact angle, and is relatively
      isotropic (no particular horizontal direction is favored). This last feature
      suggests that the bead packing acts as a perfect diffusive medium with respect to
      energy propagation.

PMID- 19391738
TI  - Annular shear of cohesionless granular materials: from the inertial to
      quasistatic regime.
AB  - Using discrete simulations, we investigate the behavior of a model granular
      material within an annular shear cell. Specifically, two-dimensional assemblies
      of disks are placed between two circular walls, the inner one rotating with
      prescribed angular velocity, while the outer one may expand or shrink and
      maintains a constant radial pressure. Focusing on steady state flows, we
      delineate in parameter space the range of applicability of the recently
      introduced constitutive laws for sheared granular materials (based on the
      inertial number). We discuss the two origins of the stronger strain rates
      observed near the inner boundary, the vicinity of the wall and the heteregeneous
      stress field in a Couette cell. Above a certain velocity, an inertial region
      develops near the inner wall, to which the known constitutive laws apply, with
      suitable corrections due to wall slip, for small enough stress gradients. Away
      from the inner wall, slow, apparently unbounded creep takes place in the
      nominally solid material, although its density and shear to normal stress ratio
      are on the jammed side of the critical values. In addition to rheological
      characterizations, our simulations provide microscopic information on the contact
      network and velocity fluctuations that is potentially useful to assess
      theoretical approaches.

PMID- 19391739
TI  - Clustering and phases of compartmentalized granular gases.
AB  - This paper experimentally investigates the clustering conditions for
      compartmentalized monodisperse granular gases, determining the critical particle
      number and condensation granular temperature at the gas-clustering transition.
      When one heavier intruding particle is added to a monodisperse gas, it is found
      that the condensation temperature decreases with the ratio of the mass of the
      intruding particle to that of the background particle. This phenomenon can be
      mathematically characterized by a proposed linear relation, which is reminiscent
      of a relation between the freezing point depression for a solvent and the
      concentration of an added solute. Finally we perform various tests by changing
      the numbers of two types of particles in bidisperse granular mixtures to
      construct the phase diagrams, which present the range of the five different
      states, namely, homogeneous gas, unstable-gas, one-clustering, two-clustering,
      and granular oscillation states.

PMID- 19391740
TI  - Normal modes in model jammed systems in three dimensions.
AB  - Vibrational spectra and normal modes of mechanically stable particle packings in
      three dimensions are analyzed over a range of compressions, from near the jamming
      transition, where the packings lose their rigidity, to far above it. At high
      frequency, the normal modes are localized at all compressions. At low frequency,
      the nature of the modes depends somewhat on compression. At large compressions,
      far from the transition, the lowest-frequency normal modes have some plane-wave
      character, though less than one would expect for a crystalline or isotropic
      solid. At low compressions near the jamming transition, the lowest-frequency
      modes are neither plane-wave-like nor localized. We characterize these
      differences, highlighting the unusual dispersion behavior that emerges for
      marginally jammed solids.

PMID- 19391741
TI  - Shear thinning of nanoparticle suspensions.
AB  - Results of large scale nonequilibrium molecular dynamics simulations are
      presented for nanoparticles in an explicit solvent. The nanoparticles are modeled
      as a uniform distribution of Lennard-Jones particles, while the solvent is
      represented by standard Lennard-Jones particles. We present results for the shear
      rheology of spherical nanoparticles of diameter 10 times that of the solvent for
      a range of nanoparticle volume fractions. By varying the strength of the
      interactions between nanoparticles and with the solvent, this system can be used
      to model colloidal gels and glasses as well as hard spherelike nanoparticles.
      Effect of including the solvent explictly is demonstrated by comparing the pair
      correlation function of nanoparticles to that in an implicit solvent. The shear
      rheology for dumbbell nanoparticles made of two fused spheres is similar to that
      of single nanoparticle.

PMID- 19391742
TI  - Phase diagram of polydisperse Na-fluorohectorite-water suspensions: a synchrotron
      small-angle x-ray scattering study.
AB  - Systems of platelet-shaped nanostacks of the synthetic clay Na-fluorohectorite,
      suspended in saline solutions of various salt concentrations, exhibit a rich
      phase behavior with up to four phases coexisting in a single sample tube. They
      are studied here using small-angle x-ray scattering: the anisotropy of the
      obtained images is quantified, and, together with x-ray absorption measurements,
      this provides a precise determination of the phase boundaries, as well as a
      measure of the orientational ordering of the clay colloids in the various gel
      phases. The coexistence of different phases results from a sedimentation-induced
      vertical gradient in particle fraction. Quantitative relation of the vertical
      coordinate to the clay particle fraction in these samples allows determination of
      a phase diagram for these Na-fluorohectorite systems, as a function of the
      particle fraction and salt concentration.

PMID- 19391743
TI  - Phenomenological description of phase inversion.
AB  - We propose an extended Ginzburg-Landau model for a description of the ambivalence
      region associated with the phenomenon of phase inversion observed in dispersed
      water-oil flow through a pipe. In analogy to the classical mean-field theory of
      phase transitions, it is shown that a good quantitative representation of the
      ambivalence region is obtained by using the injected phase volume fraction and a
      friction factor as the appropriate physical parameters.

PMID- 19391744
TI  - Critical heat flux around strongly heated nanoparticles.
AB  - We study heat transfer from a heated nanoparticle into surrounding fluid using
      molecular dynamics simulations. We show that the fluid next to the nanoparticle
      can be heated well above its boiling point without a phase change. Under
      increasing nanoparticle temperature, the heat flux saturates, which is in sharp
      contrast with the case of flat interfaces, where a critical heat flux is observed
      followed by development of a vapor layer and heat flux drop. These differences in
      heat transfer are explained by the curvature-induced pressure close to the
      nanoparticle, which inhibits boiling. When the nanoparticle temperature is much
      larger than the critical fluid temperature, a very large temperature gradient
      develops, resulting in close to ambient temperature just a radius away from the
      particle surface. The behavior reported allows us to interpret recent experiments
      where nanoparticles can be heated up to the melting point, without observing
      boiling of the surrounding liquid.

PMID- 19391745
TI  - Structure of ferrofluid nanofilms in homogeneous magnetic fields.
AB  - We report molecular dynamics simulations results for model ferrofluid films
      subject to an external, homogeneous magnetic field directed parallel or
      perpendicular to the film surfaces. The interactions between the magnetic
      nanoparticles are modeled via the Stockmayer potential. In a previous study [J.
      Jordanovic and S. H. L. Klapp, Phys. Rev. Lett. 101, 038302 (2008)] we have shown
      that an external field can control the number and internal structure of the
      layers characterizing the fluid films, in qualitative agreement with experiments.
      Here we explore the dependence of the layering effects on thermodynamic
      conditions, and we analyze the results from an energetic (microscopic and
      macroscopic) perspective. As a special case we investigate a monolayer to bilayer
      transition induced via a perpendicular field.

PMID- 19391746
TI  - Emergence of fractal behavior in condensation-driven aggregation.
AB  - We investigate the condensation-driven aggregation model that we recently
      proposed whereby an initial ensemble of chemically identical Brownian particles
      are continuously growing by condensation and at the same time undergo aggregation
      upon collision. We solved the model exactly by using scaling theory for the case
      when a particle, say of size x , grows by an amount alphax over the time it takes
      to collide with another particle of any size. It is shown that the particle size
      spectra exhibit transition to scaling c(x,t) approximately t;{-beta}varphi(xt{z})
      accompanied by the emergence of a fractal of dimension d {f}=1/(1+2alpha) . A
      remarkable feature of this model is that it is governed by a nontrivial
      conservation law, namely, the d {f}th moment of c(x,t) is time invariant. The
      reason why it remains conserved is explained. Exact values for the exponents beta
      , z , and d{f} are obtained and it is shown that they obey a generalized scaling
      relation beta=(1+d{f})z .

PMID- 19391747
TI  - Theoretical study of the magnetization dynamics of nondilute ferrofluids.
AB  - The paper is devoted to the theoretical investigation of the magnetodipolar
      interparticle interaction effect on magnetization dynamics in moderately
      concentrated ferrofluids. We consider a homogenous (without particle aggregates)
      ferrofluid consisting of identical spherical particles and employ a rigid dipole
      model, where the magnetic moment of a particle is fixed with respect to the
      particle itself. In particular, for the magnetization relaxation after the
      external field is instantly switched off, we show that the magnetodipolar
      interaction leads to the increase of the initial magnetization relaxation time.
      For the complex ac susceptibility chi(omega)=chi'(omega)+ ichi''(omega) we find
      that this interaction leads to an overall increase of chi''(omega) and shifts the
      chi''(omega) peak towards lower frequencies. Comparing results obtained with our
      analytical approach (second order virial expansion) to numerical simulation data
      (Langevin dynamics method), we demonstrate that the employed virial expansion
      approximation gives a good qualitative description of the ferrofluid
      magnetization dynamics and provides a satisfactory quantitative agreement with
      numerical simulations for the dc magnetization relaxation, up to the particle
      volume fraction phi approximately 10% , and for the ac susceptibility, up to phi
      approximately 5%.

PMID- 19391748
TI  - Complex dynamics in polymer nanocomposites.
AB  - Polymer nanocomposites offer the potential to create a new type of hybrid
      material with unique thermal, optical, or electrical properties. Understanding
      their structure, phase behavior, and dynamics is crucial for realizing such
      potentials. In this work we provide an experimental insight into the dynamics of
      such composites in terms of the temperature, wave vector, and volume fraction of
      nanoparticles, using multispeckle synchrotron x-ray photon correlation
      spectroscopy measurements on gold nanoparticles embedded in
      polymethylmethacrylate. Detailed analysis of the intermediate scattering
      functions reveals possible existence of an intrinsic length scale for dynamic
      heterogeneity in polymer nanocomposites similar to that seen in other soft
      materials like colloidal gels and glasses.

PMID- 19391749
TI  - Overdamped dynamics of paramagnetic ellipsoids in a precessing magnetic field.
AB  - We report on the dynamical behavior of paramagnetic ellipsoidal particles
      dispersed in water and floating above a flat plane when subjected to an external
      precessing magnetic field. When the magnetic field and the long axis of the
      particles are on the same plane, two clear regimes are distinguished in which the
      particles follow the magnetic modulation synchronously or asynchronously. Both
      regimes are also observed when the field precesses at an angle theta<90 degrees
      with respect to the normal to the confining plane, while the transition frequency
      increases with decreasing precession angle. We combine experimental observations
      with a theoretical model to characterize the particle dynamics. The possibility
      to control and/or reorient microscopic elongated particles by changing the
      frequency or strength of the applied field makes them suitable in microfluidic
      devices such as microgates for microchannels or active fluid mixers when placed
      close to channel junctions.

PMID- 19391750
TI  - Spatial correlations in sheared isothermal liquids: from elastic particles to
      granular particles.
AB  - Spatial correlations in sheared isothermal liquids for both elastic and granular
      cases are theoretically investigated. Using the generalized fluctuating
      hydrodynamics, correlation functions for both the microscopic scale and the
      macroscopic scale are obtained. We find the existence of long-range correlations
      obeying power laws. The validity of our theoretical predictions has been verified
      from molecular-dynamics simulation.

PMID- 19391751
TI  - Three-point susceptibilities chi(n) (k;t) and chi(n)s (k;t): mode-coupling
      approximation.
AB  - Recently, it was argued that a three-point susceptibility equal to the density
      derivative of the intermediate scattering function, chi{n}(k;t)=dF(k;t)dn ,
      enters into an expression for the divergent part of an integrated four-point
      dynamic density correlation function of a colloidal suspension [Berthier, J.
      Chem. Phys. 126, 184503 (2007)]. We show that, within the mode-coupling theory,
      the equation of motion for chi{n}(k;t) is essentially identical as the equation
      of motion for the q-->0 limit of the three-point susceptibility chi{q}(k;t)
      introduced by Biroli [Phys. Rev. Lett. 97, 195701 (2006)]. We present a numerical
      solution of the equation of motion for chi{n}(k;t) . We also derive and
      numerically solve an equation of motion for the density derivative of the self
      intermediate scattering function, chi_{n};{s}(k;t)=dF;{s}(k;t)dn . We contrast
      the wave vector dependence of chi{n}(k;t) and chi{n};{s}(k;t) .

PMID- 19391752
TI  - Fluctuating nonlinear hydrodynamics does not support an ergodic-nonergodic
      transition.
AB  - Despite its appeal, real and simulated glass forming systems do not undergo an
      ergodic-nonergodic (ENE) transition. We reconsider whether the fluctuating
      nonlinear hydrodynamics (FNH) model for this system, introduced by us in 1986,
      supports an ENE transition. Using nonperturbative arguments, with no reference to
      the hydrodynamic regime, we show that the FNH model does not support an ENE
      transition. Our results support the findings in the original paper. Assertions in
      the literature questioning the validity of the original work are shown to be in
      error.

PMID- 19391753
TI  - Structure and phase diagram of self-assembled rigid rods: equilibrium
      polydispersity and nematic ordering in two dimensions.
AB  - We investigate the influence of directional or bonding interactions on the
      structure and phase diagram of complex fluids. Using a generalization of the
      theory of associating fluids we study the interplay between the self-assembly
      process, driven by the bonding interactions, and the isotropic-nematic
      transition, driven by the anisotropic shape of the equilibrium clusters, for a
      model consisting of particles with two bonding sites and discrete orientational
      degrees of freedom. The theory is applied over a wide range of temperature and
      density in two dimensions and the results are compared with Monte Carlo
      simulations on the square lattice. The specific heat is shown to exhibit
      pronounced structure at the onset of self-assembly and at the nematic-isotropic
      transition that occur over a narrow range of temperature, at fixed density. The
      results reveal that bonding is enhanced by the nematic ordering, although a
      bonding temperature still occurs in the isotropic phase at low densities. The
      average rod length is described quantitatively in both phases, while the location
      of the ordering transition, which was found to be continuous, is predicted
      semiquantitatively by the theory.

PMID- 19391754
TI  - Reexamination of electrodiffusion time scales.
AB  - The characteristic time scales in ac ionic conduction near equilibrium are
      reassessed via consideration of a selection of one-dimensional model problems. It
      is observed that, in addition to the two basic electrodiffusion time scales,
      those of diffusion relaxation in the macroscopic- and Debye-scale domains, T and
      t{D} (the latter identical with the bulk charge relaxation time), some
      intermediate time scales are present in each system. It is concluded that, due to
      insensitivity of the electric double layers to harmonic voltage disturbances, the
      short-time response on the t{D} scale is determined by the quasielectroneutral
      bulk.

PMID- 19391755
TI  - Single-phase-field model of stepped surfaces.
AB  - We formulate a phase-field description of step dynamics on vicinal surfaces that
      makes use of a single dynamical field, at variance with previous analogous works
      in which two coupled fields are employed, namely, a phase-field proper plus the
      physical adatom concentration. Within an asymptotic sharp interface limit, our
      formulation is shown to retrieve the standard Burton-Cabrera-Frank model in the
      general case of asymmetric attachment coefficients (Ehrlich-Schwoebel effect). We
      confirm our analytical results by means of numerical simulations of our phase
      field model. Our present formulation seems particularly well adapted to
      generalization when additional physical fields are required.

PMID- 19391756
TI  - Kinetics of phase separation in thin films: lattice versus continuum models for
      solid binary mixtures.
AB  - A description of phase separation kinetics for solid binary (A,B) mixtures in
      thin film geometry based on the Kawasaki spin-exchange kinetic Ising model is
      presented in a discrete lattice molecular field formulation. It is shown that the
      model describes the interplay of wetting layer formation and lateral phase
      separation, which leads to a characteristic domain size l(t) in the directions
      parallel to the confining walls that grows according to the Lifshitz-Slyozov
      t;{13} law with time t after the quench. Near the critical point of the model,
      the description is shown to be equivalent to the standard treatments based on
      Ginzburg-Landau models. Unlike the latter, the present treatment is reliable also
      at temperatures far below criticality, where the correlation length in the bulk
      is only of the order of a lattice spacing, and steep concentration variations may
      occur near the walls, invalidating the gradient square approximation. A further
      merit is that the relation to the interaction parameters in the bulk and at the
      walls is always transparent, and the correct free energy at low temperatures is
      consistent with the time evolution by construction.

PMID- 19391757
TI  - Viscous fingering in volatile thin films.
AB  - A thin water film on a cleaved mica substrate undergoes a first-order phase
      transition between two values of film thickness. By inducing a finite evaporation
      rate of the water, the interface between the two phases develops a fingering
      instability similar to that observed in the Saffman-Taylor problem. We draw the
      connection between the two problems, and construct solutions describing the
      dynamics of evaporation in this system.

PMID- 19391758
TI  - Quantum-mechanical solution to fundamental problems of classical theory of water
      vapor nucleation.
AB  - The inconsistent temperature dependence of nucleation rates, disagreement of
      theoretical critical or onset supersaturations with experimental data, and
      insufficiently accurate predictions of nucleation rates are fundamental problems
      of the classical nucleation theory (CNT) of water vapors, which is a foundation
      of various multicomponent nucleation models widely used in the aerosol
      microphysics, physical chemistry, and chemical technology. In the present study,
      a correction to the CNT obtained from "first principles" has been derived and
      significant progress has been made in solving the fundamental problem of
      predicting nucleation rates of water vapors. The modified model with the quantum
      mechanical correction incorporated is in very good agreement with experiments
      over the full range of temperatures (T=210-290K) , saturation ratios (S=2-100) ,
      and nucleation rates (J= approximately 10{1}-10{17} cm-3).

PMID- 19391759
TI  - Nonphotochemical laser-induced nucleation of nematic phase and alignment of
      nematic director from a supercooled thermotropic liquid crystal.
AB  - A nonphotochemical laser-induced phase transition was studied in a supercooled
      4;{'}-n -pentyl-4-cyanobiphenyl (5CB, also referred to as PCB and K15) liquid
      crystal, using linearly polarized 45 ps light pulses at a wavelength of 532 nm.
      The laser induced nucleation from the metastable supercooled isotropic phase to
      the nematic phase during slow cooling (0.001 degrees C/min) and high light
      intensity (3.9 MW/cm{2}) . The resulting nematic director tended to be aligned
      along the direction of the plane of polarization of the light. At the intensities
      used, there is no observable laser-induced realignment of the director once the
      sample is in the nematic phase, nor any permanent laser-induced ordering when the
      sample is illuminated only in the stable isotropic phase during slow cooling.
      These experimental results are consistent with a mechanism based on optical Kerr
      alignment.

PMID- 19391760
TI  - Theory and computation of directional nematic phase ordering.
AB  - A computational study of morphological instabilities of a two-dimensional nematic
      front under directional growth was performed using a Landau-de Gennes-type
      quadrupolar tensor order parameter model for the first-order isotropic-nematic
      transition of 5CB (pentyl-cyanobiphenyl). A previously derived energy balance,
      taking anisotropy into account, was utilized to account for latent heat and an
      imposed morphological gradient in the time-dependent model. Simulations were
      performed using an initially homeotropic isotropic-nematic interface. Thermal
      instabilities in both the linear and nonlinear regimes were observed and compared
      to past experimental and theoretical observations. A sharp-interface model for
      the study of linear morphological instabilities, taking into account additional
      complexity resulting from liquid-crystalline order, was derived. Results from the
      sharp-interface model were compared to those from full two-dimensional simulation
      identifying the specific limitations of simplified sharp-interface models for
      this liquid-crystal system. In the nonlinear regime, secondary instabilities were
      observed to result in the formation of defects, interfacial heterogeneities, and
      bulk texture dynamics.

PMID- 19391761
TI  - Surface anchoring structure of a liquid crystal monolayer studied via dual
      polarization interferometry.
AB  - The self-organization of liquid crystal molecules of 4- n -pentyl- 4' 
      cyanobiphenyl (5CB) forming an oriented monolayer by condensation from the vapor
      phase onto a silicon oxynitride surface has been observed using the evanescent
      wave dual slab waveguide dual polarization mode interferometry (DPI) technique.
      Two distinct stages to the layer formation are observed: After the formation of a
      layer of molecules lying prone on the surface, further condensation begins to
      densify the layer and produces a gradual mutual alignment of the molecules until
      the fully condensed, fully aligned monolayer is reached. At this limit the full
      coverage 5CB monolayer on this surface and at a temperature of 25 degrees C , is
      found to be anchored with an average molecular axis polar angle of 56+/-1 degrees
      and with a measured thickness of 16.6+/-0.5A . These results are in reasonable
      agreement with the molecular dimensions provided by molecular models. The
      apparent precision and accuracy of these results resolves some wide disparity
      between earlier studies of such systems. Previous difficulties in determining
      optogeometrical properties of such ultrathin birefringent films using
      ellipsometry or in the need for complex modeling of the film layer structure
      using x-ray reflectivity are overcome in this instance. We provide a technique
      for analyzing the dual polarization data from DPI such that the bulk refractive
      index values, when known, can be used to determine the orientation and thickness
      of a layer that is on the nanometer or subnanometer scale.

PMID- 19391762
TI  - Colloid-wall interaction in a nematic liquid crystal: the mirror-image method of
      colloidal nematostatics.
AB  - The new area of nematic colloidal systems (or nematic emulsions) has been greatly
      guided by the fruitful analogy between the colloidal nematostatics and
      electrostatics. The elastic charge density representation of the colloidal
      nematostatics [V. M. Pergamenshchik and V. O. Uzunova, Eur. Phys. J. E 23, 161
      (2007); Phys. Rev. E 76, 011707 (2007)] develops this analogy at the level of
      charge density and Coulomb interaction. It shows, however, that the colloidal
      nematostatics in three dimensions substantially differs from the electrostatics
      both in its mathematical structure and physical implications: the elastic charge
      and multipoles are dyads; similar charges attract while opposite charges repel
      each other, and so on. In this paper we consider the interaction between an
      elastic charge and elastic dipole with a nematic surface (wall) at which the
      director alignment is fixed. Using the mirror image method of electrostatics as a
      guiding idea, we develop the mirror image method in the nematostatics for
      arbitrary director tilt at the wall. A wall is shown to induce a repulsive 1R{4}
      force on the elastic dipole which, in general, is accompanied by its
      reorientation. External torque on the colloid induces an elastic charge therein
      and triggers switching to the 1R{2} repulsion. The dyadic nature of an elastic
      dipole is shown to be essential: a particle-wall interaction potential cannot be
      obtained in phenomenological theories with a single component dipole. In the
      introductory sections we discuss connection between the director-mediated
      interaction in two and three dimensions and the electrostatic interaction and
      consider different symmetries of elastic dipoles. Conservation of the torque
      components exerted upon colloids is shown to play the role of Gauss' theorem and
      determines the elastic charge dyad.

PMID- 19391763
TI  - Quadrupolar particles in a nematic liquid crystal: effects of particle size and
      shape.
AB  - We investigate the effects of particle size and shape on the quadrupolar (Saturn
      ring-like) defect structures formed by a nematic liquid crystal around nm-sized
      and mum -sized particles with spherical and spherocylindrical shapes. We also
      report results for the potentials of mean force in our systems, calculated using
      a mesoscale theory for the tensor order parameter Q of the nematic. Our results
      indicate that for pairs of nm-sized particles in close proximity, the nematic
      forms "entangled hyperbolic" defect structures regardless of the shape of the
      nanoparticles. In our calculations with nanoparticles we did not observe any
      other entangled or unentangled defect structures, in contrast to what was
      reported for pairs of mum -sized spherical particles. Such a finding suggests
      that the "entangled hyperbolic" defect structures are the most stable for pairs
      of nanoparticles in close proximity. For pairs of mum -sized particles, our
      results indicate that the nematic forms entangled "figure-of-eight" defect
      structures around pairs of spheres and spherocylinders. Our results suggest that
      the transition between "entangled hyperbolic" and figure-of-eight defect
      structures takes place when the diameter of the particle is between D=100 nm and
      1 microm . We have also calculated the torques that develop when pairs of
      spherocylindrical nanoparticles in a nematic approach each other. Our
      calculations suggest that the nematic-mediated interactions between the nm-sized
      particles are fairly strong, up to 5700 k{B}T for the case of pairs of
      spherocylindrical nanoparticles arranged with their long axis parallel to each
      other. Furthermore, these interactions can make the particles to bind together at
      specific locations, and thus could be used to assemble the particles into ordered
      structures with different morphologies.

PMID- 19391764
TI  - Recovery of a reversed phase sequence in one ternary liquid-crystal-mixture
      system.
AB  - The nOHFBBB1M7 (n=10) compound, 10OHF, shows a reversed SmC{FI2}-SmC phase
      sequence, unique among all known antiferroelectric liquid crystals. This reversed
      phase sequence is stabilized when 10OHF is doped with 9OTBBB1M7(C9) or
      11OTBBB1M7(C11). In contrast, doping of the homologous members ( n=9 , 11, or 12)
      eliminates the SmC{FI2} phase. One 10OHF/11OHF mixture without the SmC{FI2} phase
      was selected for further studies. By adding C9 into this particular mixture, the
      reversed phase sequence is revived. To our surprise, even though 11OHF
      destabilizes the SmC_{FI2} phase in binary mixtures with 10OHF, it significantly
      increases the SmC_{FI2} temperature range in the 10OHF/11OHF/C9 ternary mixtures.

PMID- 19391765
TI  - Topological transformations in bipolar shells of nematic liquid crystals.
AB  - We investigate how defects in bipolar shells of liquid crystal evolve when the
      boundary conditions for the nematic director n at the outer surface of the shell
      are changed from tangential to homeotropic. When the boundary conditions for n
      are tangential, these bipolar shells are characterized by the presence of two
      pairs of boojums, one pair on each spherical surface. However, when n is
      tangential at the inner surface and perpendicular at the outer surface, only the
      innermost pair of defects remains. Interestingly, there are two possible routes
      from one shell to the other and both involve the generation of a disclination
      ring that shrinks with time, eventually disappearing. Although the process is
      reminiscent of that encountered in bulk nematic droplets, in the case of nematic
      shells the two defects on the inner surface play a relevant role in the overall
      evolution process.

PMID- 19391766
TI  - Brownian dynamics simulation of tracer diffusion in a cross-linked network.
AB  - Brownian dynamics simulation is employed to study the self-diffusion of tracer
      particles in a cross-linked gel network based on a coarse-grained bead-spring
      lattice model. Several effects are investigated including the network porosity,
      flexibility, degree of cross linking, and electrostatic interaction. For
      uncharged systems, the tracer long-time diffusivity is found to decrease with
      deceasing porosity and flexibility, but with increasing degree of cross linking.
      For charged systems, the diffusion is further hindered by the electrostatic
      interaction, regardless of whether the tracer particle and the network are
      oppositely or similarly charged. However, there exists a difference in the
      hindrance mechanism between the two cases. For the former, a substantial decrease
      in the diffusivity can occur at high network porosities due to electrostatic
      entrapment.

PMID- 19391767
TI  - Nondriven polymer translocation through a nanopore: computational evidence that
      the escape and relaxation processes are coupled.
AB  - Most of the theoretical models describing the translocation of a polymer chain
      through a nanopore use the hypothesis that the polymer is always relaxed during
      the complete process. In other words, models generally assume that the
      characteristic relaxation time of the chain is small enough compared to the
      translocation time that nonequilibrium molecular conformations can be ignored. In
      this paper, we use molecular dynamics simulations to directly test this
      hypothesis by looking at the escape time of unbiased polymer chains starting with
      different initial conditions. We find that the translocation process is not quite
      in equilibrium for the systems studied, even though the translocation time tau is
      about 10 times larger than the relaxation time tau{r}. Our most striking result
      is the observation that the last half of the chain escapes in less than
      approximately 12% of the total escape time, which implies that there is a large
      acceleration of the chain at the end of its escape from the channel.

PMID- 19391768
TI  - Scaling of the rupture dynamics of polymer chains pulled at one end at a constant
      rate.
AB  - We consider the rupture dynamics of a homopolymer chain pulled at one end at a
      constant loading rate r . Compared to single bond breaking, the existence of the
      chain introduces two aspects into rupture dynamics: The non-Markovian aspect in
      the barrier crossing and the slow down of the force propagation to the breakable
      bond. The relative impact of both these processes is investigated, and the second
      one was found to be the most important at moderate loading rates. The most
      probable rupture force is found to decrease with the number of bonds as f{max}
      proportional, variant-[ln(const N/r)]2/3 and finally to approach a saturation
      value independent on N . All of our analytical findings are confirmed by
      extensive numerical simulations.

PMID- 19391769
TI  - Freely relaxing polymers remember how they were straightened.
AB  - The relaxation of initially straight semiflexible polymers has been discussed
      mainly with respect to the longest relaxation time. The biologically relevant
      nonequilibrium dynamics on shorter times is comparatively poorly understood,
      partly because "initially straight" can be realized in manifold ways. Combining
      Brownian dynamics simulations and systematic theory, we demonstrate how different
      experimental preparations give rise to specific short-time and universal long
      time dynamics. We also discuss boundary effects and the onset of the stretch-coil
      transition.

PMID- 19391770
TI  - Universal version of density-functional theory for polymers with complex
      architecture.
AB  - We propose a density-functional theory for inhomogeneous polyatomic fluids with
      complex architecture by introducing a different representation for the polymers.
      This representation gives an efficient hierarchical algorithm to calculate the
      direct bonding connectivity integral for polymers with complex architecture, such
      as linear, star, branched, and dendritic structures. A comparison with the
      available simulated data for linear and star polymers confirms the accuracy of
      the present theory in reproducing the density profiles of the two types of
      polymer in the slits. By using the proposed algorithm, we also explore
      partitioning coefficients of polymers of different architectures in a slit, and
      find that the partitioning coefficients of branched, star, and dendrimer forms of
      22-mers decrease to a minimum at extremely low packing fraction, and then
      increase monotonically with packing fraction. Moreover, it is found that it is
      more difficult for a linear polymer of 22-mers to enter the slit than for
      branched, star, and dendritic polymers. In addition, we also investigate the self
      assembly of diblock copolymers with different tails in a slit. It is found that
      the linear copolymer self-assembles into a trilayer film structure, while
      copolymers with branched and dendritic tails self-assemble into a five-layer film
      structure. Interestingly, the copolymer with a star tail self-assembles into a
      trilayer film structure, and then the trilayer structure evolves into a five
      layer structure with increase of the bulk packing fraction in the case studied.

PMID- 19391771
TI  - Universality in the diffusion of knots.
AB  - We have evaluated a universal ratio between diffusion constants of the ring
      polymer with a given knot K and a linear polymer with the same molecular weight
      in solution through the Brownian dynamics under hydrodynamic interaction. The
      ratio is found to be constant with respect to the number of monomers, N , and
      hence the estimate at some N should be valid practically over a wide range of N
      for various polymer models. Interestingly, the ratio is determined by the average
      crossing number (N{AC}) of an ideal conformation of knotted curve K , i.e., that
      of the ideal knot. The N{AC} of ideal knots should therefore be fundamental in
      the dynamics of knots.

PMID- 19391772
TI  - Entropic trap, surface-mediated combing, and assembly of DNA molecules within
      submicrometer interfacial confinement.
AB  - In this work, we report an alternative microfluidic approach to studying the
      motion of single DNA molecules in an electric field. Making use of a closely
      fitting droplet in a microchannel, DNA molecules can be confined within the
      submicrometer film beneath the droplet. Several dynamic events at the single
      molecule level and self-assembly phenomena at mesoscales are observed. We find
      that DNA can be trapped and stretched at the entrance to the film due to entropic
      effects. After escaping the trap, DNA can exhibit cyclic stick-slip motion with a
      field-dependent mobility owing to interim anchoring to surface surfactants. We
      also observe that, by incorporation of surface modification effects with plasma
      oxidation, DNA can be combed onto the channel surface at sufficiently high
      fields. In this case, upon removing the field, as-stretched DNA molecules can
      aggregate into larger clusters or self-organize into mesoscale bundles aligned in
      the direction of the previously applied field. The physics underlying these
      phenomena is discussed in detail.

PMID- 19391773
TI  - Noise-driven attractor switching device.
AB  - Problems with artificial neural networks originate from their deterministic
      nature and inevitable prior learnings, resulting in inadequate adaptability
      against unpredictable, abrupt environmental change. Here we show that a
      stochastically excitable threshold unit can be utilized by these systems to
      partially overcome the environmental change. Using an excitable threshold system,
      attractors were created that represent quasiequilibrium states into which a
      system settles until disrupted by environmental change. Furthermore, noise-driven
      attractor stabilization and switching were embodied by inhibitory connections.
      Noise works as a power source to stabilize and switch attractors, and endows the
      system with hysteresis behavior that resembles that of stereopsis and binocular
      rivalry in the human visual cortex. A canonical model of the ring network with
      inhibitory connections composed of class 1 neurons also shows properties that are
      similar to the simple threshold system.

PMID- 19391774
TI  - Three-dimensional quantification of structures in trabecular bone using measures
      of complexity.
AB  - The study of pathological changes of bone is an important task in diagnostic
      procedures of patients with metabolic bone diseases such as osteoporosis as well
      as in monitoring the health state of astronauts during long-term space flights.
      The recent availability of high-resolution three-dimensional (3D) imaging of bone
      challenges the development of data analysis techniques able to assess changes of
      the 3D microarchitecture of trabecular bone. We introduce an approach based on
      spatial geometrical properties and define structural measures of complexity for
      3D image analysis. These measures evaluate different aspects of organization and
      complexity of 3D structures, such as complexity of its surface or shape
      variability. We apply these measures to 3D data acquired by high-resolution
      microcomputed tomography (microCT) from human proximal tibiae and lumbar
      vertebrae at different stages of osteoporotic bone loss. The outcome is compared
      to the results of conventional static histomorphometry and exhibits clear
      relationships between the analyzed geometrical features of trabecular bone and
      loss of bone density, but also indicate that the measures reveal additional
      information about the structural composition of bone, which were not revealed by
      the static histomorphometry. Finally, we have studied the dependency of the
      developed measures of complexity on the spatial resolution of the microCT data
      sets.

PMID- 19391775
TI  - Dynamical phase transitions in periodically driven model neurons.
AB  - Transitions between dynamical states in integrate-and-fire neuron models with
      periodic stimuli result from tangent or discontinuous bifurcations of a return
      map. We study their characteristic scaling laws and show that discontinuous
      bifurcations exhibit a kind of phase transition intermediate between continuous
      and first order. In the model-independent spirit of our analysis we show that a
      six-dimensional (6D) gating variable model with an attracting limit cycle has
      similar phase transitions, governed by a 1D return map. This reduction to 1D map
      dynamics should extend to real neurons in a periodic current clamp setting.

PMID- 19391776
TI  - Serial correlation in neural spike trains: experimental evidence, stochastic
      modeling, and single neuron variability.
AB  - The activity of spiking neurons is frequently described by renewal point process
      models that assume the statistical independence and identical distribution of the
      intervals between action potentials. However, the assumption of independent
      intervals must be questioned for many different types of neurons. We review
      experimental studies that reported the feature of a negative serial correlation
      of neighboring intervals, commonly observed in neurons in the sensory periphery
      as well as in central neurons, notably in the mammalian cortex. In our
      experiments we observed the same short-lived negative serial dependence of
      intervals in the spontaneous activity of mushroom body extrinsic neurons in the
      honeybee. To model serial interval correlations of arbitrary lags, we suggest a
      family of autoregressive point processes. Its marginal interval distribution is
      described by the generalized gamma model, which includes as special cases the log
      normal and gamma distributions, which have been widely used to characterize
      regular spiking neurons. In numeric simulations we investigated how serial
      correlation affects the variance of the neural spike count. We show that the
      experimentally confirmed negative correlation reduces single-neuron variability,
      as quantified by the Fano factor, by up to 50%, which favors the transmission of
      a rate code. We argue that the feature of a negative serial correlation is likely
      to be common to the class of spike-frequency-adapting neurons and that it might
      have been largely overlooked in extracellular single-unit recordings due to spike
      sorting errors.

PMID- 19391777
TI  - Resonant response to temperature modulation for enzymatic dynamics
      characterization.
AB  - We consider enzymes involved in a three-state Michaelis-Menten kinetics and
      submitted to well-chosen temperature modulations of small amplitude. From the
      first-order amplitudes of concentration oscillations, we design a response
      function that is maximum for targeted values of the chemical relaxation times.
      This resonant function can be used to screen a large set of enzymes and identify
      the one governed by the desired kinetics. The method gives access to all the
      dynamical parameters of the targeted enzyme without resorting to a fit. We show
      how to estimate the precision of this parameter determination and give some hints
      for experimental validation.

PMID- 19391778
TI  - Spectral sideband produced by a hemispherical concave multilayer on the African
      shield-bug Calidea panaethiopica (Scutelleridae).
AB  - The African shield-backed bug Calidea panaethiopica is a very colorful insect
      which produces a range of iridescent yellow, green, and blue reflections. The
      cuticle of the dorsal side of the insect, on the shield, the prothorax and part
      of the head, is pricked of uniformly distributed hemispherical hollow cavities a
      few tens micrometers deep. Under normal illumination and viewing the insect's
      muffin-tin shaped surface gives rise to two distinct colors: a yellow spot
      arising from the bottom of the well and a blue annular cloud that appears to
      float around the yellow spot. This effect is explained by multiple reflections on
      a hemispherical Bragg mirror with a mesoscopic curvature. A multiscale computing
      methodology was found to be needed to evaluate the reflection spectrum for such a
      curved multilayer. This multiscale approach is very general and should be useful
      for dealing with visual effects in many natural and artificial systems.

PMID- 19391779
TI  - Transitions in a self-propelled-particles model with coupling of accelerations.
AB  - We consider a three-dimensional, generalized version of the original self
      propelled-particles (SPP) model for collective motion. By extending the factors
      influencing the ordering, we investigate the case when the movement of the SPPs
      depends on both the velocity and the acceleration of the neighboring particles,
      instead of being determined solely by the former one. By changing the value of a
      weight parameter s determining the relative influence of the velocity and the
      acceleration terms, the system undergoes a kinetic phase transition as a function
      of a behavioral pattern. Below a critical value of s the system exhibits
      disordered motion, while above it the dynamics resembles that of the SPP model.
      We show that the critical value of the strategy variable could correspond to an
      evolutionary optimum in the sense that the information exchange between the units
      of the system is maximal in this point.

PMID- 19391780
TI  - Structured information in small-world neural networks.
AB  - The retrieval abilities of spatially uniform attractor networks can be measured
      by the global overlap between patterns and neural states. However, we found that
      nonuniform networks, for instance, small-world networks, can retrieve fragments
      of patterns (blocks) without performing global retrieval. We propose a way to
      measure the local retrieval using a parameter that is related to the fluctuation
      of the block overlaps. Simulation of neural dynamics shows a competition between
      local and global retrieval. The phase diagram shows a transition from local
      retrieval to global retrieval when the storage ratio increases and the topology
      becomes more random. A theoretical approach confirms the simulation results and
      predicts that the stability of blocks can be improved by dilution.

PMID- 19391781
TI  - Deformation of biological cells in the acoustic field of an oscillating bubble.
AB  - In this work we develop a theoretical framework of the interaction of
      microbubbles with bacteria in the ultrasound field using a shell model of the
      bacteria, following an approach developed previously [P. V. Zinin, Phys. Rev. E
      72, 61907 (2005)]. Within the shell model, the motion of the cell in an
      ultrasonic field is determined by the motion of three components: the internal
      viscous fluid, a thin elastic shell, and the surrounding viscous fluid. Several
      conclusions can be drawn from the modeling of sound interaction with a biological
      cell: (a) the characteristics of a cell's oscillations in an ultrasonic field are
      determined both by the elastic properties of the shell the viscosities of all
      components of the system, (b) for dipole quadrupole oscillations the cell's shell
      deforms due to a change in the shell area this oscillation depends on the surface
      area modulus K{A} , (c) the relative change in the area has a maximum at
      frequency f{K} approximately 1/2pi square root[K{A}(rhoa;{3})] , where a is the
      cell's radius and rho is its density. It was predicted that deformation of the
      cell wall at the frequency f{K} is high enough to rupture small bacteria such as
      E . coli in which the quality factor of natural vibrations is less than 1 (Q<1).
      For bacteria with high value quality factors (Q>1) , the area deformation has a
      strong peak near a resonance frequency f{K} however, the value of the deformation
      near the resonance frequency is not high enough to produce sufficient mechanical
      effect. The theoretical framework developed in this work can be extended for
      describing the deformation of a biological cell under any arbitrary, external
      periodic force including radiation forces unduced by acoustical (acoustical
      levitation) or optical waves (optical tweezers).

PMID- 19391782
TI  - Derivation and analysis of an ordinary differential equation mean-field model for
      studying clinically recorded epilepsy dynamics.
AB  - In this paper we describe how an ordinary differential equation model of
      corticothalamic interactions may be obtained from a more general system of delay
      differential equations. We demonstrate that transitions to epileptic dynamics via
      changes in system parameters are qualitatively the same as in the original model
      with delay, as well as demonstrating that the onset of epileptic activity may
      arise due to regions of bistability. Hence, the model presents in one unique
      framework, two competing theories for the genesis of epileptiform activity.
      Similarities between model transitions and clinical data are presented and we
      argue that statistics obtained from, and a parameter estimation of this model may
      be a potential means of classifying and predicting the onset and offset of
      seizure activity.

PMID- 19391783
TI  - Small-angle neutron scattering study of structure and kinetics of temperature
      induced protein gelation.
AB  - The phase diagram, structural evolution, and kinetics of temperature-induced
      protein gelation of protein Bovine Serum Albumin (BSA) have been studied as a
      function of solution pH and protein concentration. The protein gelation
      temperature represents the onset of turbidity in the protein solution, which
      increases significantly with increasing pH beyond the isoelectric pH of the
      protein molecule. On the other hand, the gelation temperature decreases with an
      increase in protein concentration only in the low-protein-concentration regime
      and shows a small increasing trend at higher protein concentrations. The
      structural evolution and kinetics of protein gelation have been studied using
      small-angle neutron scattering. The structure of the protein molecule remains
      stable up to temperatures very close to the gelation temperature. On increasing
      the temperature above the gelation temperature, the protein solution exhibits a
      fractal structure, an indication of gel formation due to aggregation. The fractal
      dimension of the gel increases with increasing temperature, suggesting an
      increase in branching between the aggregates, which leads to stronger gels. The
      increase in both solution pH and protein concentration is found to delay the
      growth in the fractal structure and its saturation. The kinetics of gelation has
      been studied using the temperature-jump process of heating. It is found that the
      structure of the protein gels remains invariant after the heating time (
      approximately 1 min), indicating a rapid formation of gel structure within this
      time. The protein gels prepared through gradual and temperature-jump heating
      routes do not always show the same structure. In particular, at higher
      temperatures (e.g., 85 degrees C ), while gradual heating shows a fractal
      structure, there is collapse of such fractal structure during temperature-jump
      heating.

PMID- 19391784
TI  - Potential formulation of sleep dynamics.
AB  - A physiologically based model of the mechanisms that control the human sleep-wake
      cycle is formulated in terms of an equivalent nonconservative mechanical
      potential. The potential is analytically simplified and reduced to a quartic two
      well potential, matching the bifurcation structure of the original model. This
      yields a dynamics-based model that is analytically simpler and has fewer
      parameters than the original model, allowing easier fitting to experimental data.
      This model is first demonstrated to semiquantitatively match the dynamics of the
      physiologically based model from which it is derived, and is then fitted directly
      to a set of experimentally derived criteria. These criteria place rigorous
      constraints on the parameter values, and within these constraints the model is
      shown to reproduce normal sleep-wake dynamics and recovery from sleep
      deprivation. Furthermore, this approach enables insights into the dynamics by
      direct analogies to phenomena in well studied mechanical systems. These include
      the relation between friction in the mechanical system and the timecourse of
      neurotransmitter action, and the possible relation between stochastic resonance
      and napping behavior. The model derived here also serves as a platform for future
      investigations of sleep-wake phenomena from a dynamical perspective.

PMID- 19391785
TI  - Massively parallel computation of absolute binding free energy with well
      equilibrated states.
AB  - A force field formulator for organic molecules (FF-FOM) was developed to assign
      bond, angle, and dihedral parameters to arbitrary organic molecules in a unified
      manner including proteins and nucleic acids. With the unified force field
      parametrization we performed massively parallel computations of absolute binding
      free energies for pharmaceutical target proteins and ligands. Compared with the
      previous calculation with the ff99 force field in the Amber simulation package
      (Amber99) and the ligand charges produced by the Austin Model 1 bond charge
      correction (AM1-BCC), the unified parametrization gave better absolute binding
      energies for the FK506 binding protein (FKBP) and ligand system. Our method is
      based on extensive work measurement between thermodynamic states to calculate the
      free energy difference and it is also the same as the traditional free energy
      perturbation. There are important requirements for accurate calculations. The
      first is a well-equilibrated bound structure including the conformational change
      of the protein induced by the binding of the ligand. The second requirement is
      the convergence of the work distribution with a sufficient number of trajectories
      and dense spacing of the coupling constant between the ligand and the rest of the
      system. Finally, the most important requirement is the force field
      parametrization.

PMID- 19391786
TI  - Stability of a model food web.
AB  - We investigate numerically the stability of a model food web, introduced by Nunes
      Amaral and Meyer [Phys. Rev. Lett. 82, 652 (1999)]. The model describes a system
      of species located in niches at several levels. Upper level species are predating
      on those from a lower level. We show that the model web is more stable when it is
      larger, although the number of niches is more important than the number of
      levels. The food web is self-organizing itself, trying to reach a certain degree
      of complexity, i.e., number of species and links among them. If the system cannot
      achieve this state, it will go extinct. We demonstrate that the average number of
      links per species and the reduced number of species depend in the same way on the
      number of niches. We also determine how the stability of the food web depends on
      another parameter of the model, the killing probability. Despite keeping the
      ratio of the creation and killing probabilities constant, increasing the latter
      reduces significantly the stability of the model food web. We show that
      connectance dependence on the number of niches has a power-type character, which
      agrees with the field data, and that it decreases with the number of species also
      as a power-type function.

PMID- 19391787
TI  - Mechanics model for actin-based motility.
AB  - We present here a mechanics model for the force generation by actin
      polymerization. The possible adhesions between the actin filaments and the load
      surface, as well as the nucleation and capping of filament tips, are included in
      this model on top of the well-known elastic Brownian ratchet formulation. A
      closed form solution is provided from which the force-velocity relationship,
      summarizing the mechanics of polymerization, can be drawn. Model predictions on
      the velocity of moving beads driven by actin polymerization are consistent with
      experiment observations. This model also seems capable of explaining the enhanced
      actin-based motility of Listeria monocytogenes and beads by the presence of
      Vasodilator-stimulated phosphoprotein, as observed in recent experiments.

PMID- 19391788
TI  - Quantum disordering versus melting in Lennard-Jones clusters.
AB  - The ground states of Lennard-Jones clusters for sizes up to n=147 are estimated
      as a function of the de Boer quantum delocalization length Lambda , and the n
      Lambda "phase diagram" is constructed. The increase in Lambda favors more
      disordered and diffuse structures over more symmetric and compact ones,
      eventually making the liquidlike motif most energetically favorable. The analogy
      between the quantum- and thermally-induced structural transitions is explored.

PMID- 19391789
TI  - Rolling friction on a granular medium.
AB  - We present experimental results for the rolling of spheres on a granular bed. We
      use two sets of glass and steel spheres with varying diameters and a high-speed
      camera to follow the motion of the spheres. Despite the complex phenomena
      occurring during the rolling, the results show a friction coefficient nearly
      independent of the velocity (0.45-0.5 for glass and 0.6-0.65 for steel). It is
      found that for a given sphere density, the large spheres reach a longer distance,
      a result that may also help explain the rock sorting along natural stone
      accumulations at the foot of mountain slopes.

PMID- 19391790
TI  - Nematic cells with quasicrystalline-patterned alignment layers.
AB  - Nematic cells with surface anchoring fields exhibiting quasicrystalline symmetry
      can be fabricated using linear photopolymerizable polymers and suitable optics.
      Using the Lebwohl-Lasher model we carry out Monte Carlo simulations of a nematic
      cell where the top and bottom surfaces have an anchoring field with the symmetry
      of a periodic approximant to a Penrose lattice. We show that the anchoring field
      has point topological defects, nearly all with topological charge +/-1 . Our
      simulations, which assume infinitely strong anchoring of the nematic to the
      anchoring field, show that half-integer disclination lines emerge from the point
      defects and either traverse the thickness of the cell for small cell thicknesses,
      hug the patterned surfaces for large thicknesses, or combine these behaviors for
      intermediate thicknesses. We show that estimates of the values of the thicknesses
      separating these three behaviors can be obtained using the properties of Penrose
      tilings.

PMID- 19391791
TI  - In situ microextraction method to determine the viscosity of biofluid in
      threadlike structures on the surfaces of mammalian organs.
AB  - We report a method to measure the viscosity of microL volumes of biofluid
      obtained from threadlike structures (NTSs) on the surfaces of mammalian (rabbit)
      internal organs. The fluid was mechanically microextracted in situ from NTSs on
      the organ surfaces by a glass capillary connected to an extractor. From the
      Brownian motion of the 0.8+/-0.1microm diameter granules in the extracted fluid,
      the fluid viscosity was determined to be 1.4+/-0.1mPa s at room temperature. This
      viscosity is comparable to the viscosity of rabbit blood plasma.

PMID- 19391792
TI  - How complex is quantum motion?
AB  - In classical mechanics the complexity of a dynamical system is characterized by
      the rate of local exponential instability which effaces the memory of initial
      conditions and leads to practical irreversibility. In striking contrast, quantum
      mechanics appears to exhibit strong memory of the initial state. Here we
      introduce a notion of complexity for a quantum system and relate it to its
      stability and reversibility properties.

PMID- 19391793
TI  - Border collision bifurcations, snap-back repellers, and chaos.
AB  - The normal form for codimension 1 border collision bifurcations of fixed points
      of discrete time piecewise smooth dynamical systems is considered in the unstable
      case. We show that in appropriate parameter regions there is a snap-back repeller
      immediately after the bifurcation, and hence that the bifurcation creates chaos.
      Although the chaotic solutions are repellers they may explain observations, and
      this is illustrated through an example.

PMID- 19391794
TI  - Scaling laws in the quantum-to-classical transition in chaotic systems.
AB  - We study the quantum-to-classical transition in a chaotic system surrounded by a
      diffusive environment. First, we analyze the emergence of classicality when it is
      monitored by the Renyi entropy, a measure of the entanglement of a system with
      its environment. We show that the Renyi entropy has a transition from quantum to
      classical behavior that scales with heff2D, where heff is the effective Planck
      constant and D is the strength of the noise. However, it was recently shown that
      a different scaling law controls the quantum-to-classical transition when it is
      measured comparing the corresponding phase-space distributions. Then, we discuss
      the meaning of both scalings in the precise definition of a frontier between the
      classical and quantum behaviors. Finally, we show that there are quantum
      coherences that the Renyi entropy is unable to detect, which questions its use in
      studies of decoherence.

PMID- 19391795
TI  - Spatiotemporal perspective on the decay of turbulence in wall-bounded flows.
AB  - By use of a reduced model focusing on the in-plane dependence of plane Couette
      flow, it is shown that the turbulent-->laminar relaxation process can be
      understood as a nucleation problem similar to that occurring at a thermodynamic
      first-order phase transition. The approach, apt to deal with the large extension
      of the system considered, challenges the current interpretation in terms of
      chaotic transients typical of temporal chaos. The study of the distribution of
      the sizes of laminar domains embedded in turbulent flow proves that an abrupt
      transition from sustained spatiotemporal chaos to laminar flow can take place at
      some given value of the Reynolds number Rlow, whether or not the local chaos
      lifetime, as envisioned within low-dimensional dynamical systems theory, diverges
      at finite R beyond Rlow.

PMID- 19391796
TI  - Influence of gravitational forces and fluid flows on the shape of surfaces of a
      viscous fluid of capillary size.
AB  - The Navier-Stokes equations and boundary conditions for viscous fluids of
      capillary size are formulated in curvilinear coordinates associated with a
      geometry of the fluid-gas interface. As a result, the fluid dynamics of drops and
      menisci, which takes into account the influence of gravitational forces and flows
      on the surface shape, can be described. This gives a convenient basis for
      numerical studies. Estimations of the effects are presented for the case of an
      evaporating sessile drop.

PMID- 19391797
TI  - Extreme events in discrete nonlinear lattices.
AB  - We perform statistical analysis on discrete nonlinear waves generated through
      modulational instability in the context of the Salerno model that interpolates
      between the integrable Ablowitz-Ladik (AL) equation and the nonintegrable
      discrete nonlinear Schrodinger equation. We focus on extreme events in the form
      of discrete rogue or freak waves that may arise as a result of rapid coalescence
      of discrete breathers or other nonlinear interaction processes. We find power law
      dependence in the wave amplitude distribution accompanied by an enhanced
      probability for freak events close to the integrable limit of the equation. A
      characteristic peak in the extreme event probability appears that is attributed
      to the onset of interaction of the discrete solitons of the AL equation and the
      accompanied transition from the local to the global stochasticity monitored
      through the positive Lyapunov exponent of a nonlinear map.

PMID- 19391798
TI  - Solitons with cubic and quintic nonlinearities modulated in space and time.
AB  - This work deals with soliton solutions of the nonlinear Schrodinger equation with
      cubic and quintic nonlinearities. We extend the procedure put forward in a recent
      paper [J. Belmonte-Beitia, Phys. Rev. Lett. 100, 164102 (2008)], and we solve the
      equation in the presence of a linear background and cubic and quintic
      interactions which are modulated in space and time. As a result, we show how a
      simple parameter can be used to generate brightlike or darklike localized
      nonlinear waves which oscillate in several distinct ways, driven by the space and
      time dependence of the parameters that control the trapping potential and the
      cubic and quintic nonlinearities.

PMID- 19391799
TI  - Statistical kinetic treatment of relativistic binary collisions.
AB  - In particle-based algorithms, the effect of binary collisions is commonly
      described in a statistical way, using Monte Carlo techniques. It is shown that,
      in the relativistic regime, stringent constraints should be considered on the
      sampling of particle pairs for collision, which are critical to ensure physically
      meaningful results, and that nonrelativistic sampling criteria (e.g., uniform
      random pairing) yield qualitatively wrong results, including equilibrium
      distributions that differ from the theoretical Juttner distribution. A general
      procedure for relativistically consistent algorithms is provided, and verified
      with three-dimensional Monte Carlo simulations, thus opening the way to the
      numerical exploration of the statistical properties of collisional relativistic
      systems.

PMID- 19391800
TI  - Time evolution of epidemic disease on finite and infinite networks.
AB  - Mathematical models of infectious diseases, which are in principle analytically
      tractable, use two general approaches. The first approach, generally known as
      compartmental modeling, addresses the time evolution of disease propagation at
      the expense of simplifying the pattern of transmission. The second approach uses
      network theory to incorporate detailed information pertaining to the underlying
      contact structure among individuals while disregarding the progression of time
      during outbreaks. So far, the only alternative that enables the integration of
      both aspects of disease propagation simultaneously while preserving the variety
      of outcomes has been to abandon the analytical approach and rely on computer
      simulations. We offer an analytical framework, that incorporates both the
      complexity of contact network structure and the time progression of disease
      spread. Furthermore, we demonstrate that this framework is equally effective on
      finite- and "infinite"-size networks. This formalism can be equally applied to
      similar percolation phenomena on networks in other areas of science and
      technology.

PMID- 19391801
TI  - Modularity clustering is force-directed layout.
AB  - Two natural and widely used representations for the community structure of
      networks are clusterings, which partition the vertex set into disjoint subsets,
      and layouts, which assign the vertices to positions in a metric space. This paper
      unifies prominent characterizations of layout quality and clustering quality, by
      showing that energy models of pairwise attraction and repulsion subsume Newman
      and Girvan's modularity measure. Layouts with optimal energy are relaxations of,
      and are thus consistent with, clusterings with optimal modularity, which is of
      practical relevance because the two representations are complementary and often
      used together.

PMID- 19391802
TI  - Thermal conductivity and phase separation of the crust of accreting neutron
      stars.
AB  - Recently, crust cooling times have been measured for neutron stars after extended
      outbursts. These observations are very sensitive to the thermal conductivity
      kappa of the crust and strongly suggest that kappa is large. We perform molecular
      dynamics simulations of the structure of the crust of an accreting neutron star
      using a complex composition that includes many impurities. The composition comes
      from simulations of rapid proton capture nucleosynthesis followed by electron
      captures. We find that the thermal conductivity is reduced by impurity
      scattering. In addition, we find phase separation. Some impurities with low
      atomic number Z are concentrated in a subregion of the simulation volume. For our
      composition, the solid crust must separate into regions of different
      compositions. This could lead to an asymmetric star with a quadrupole
      deformation. Observations of crust cooling can constrain impurity concentrations.

PMID- 19391803
TI  - Renormalization flows in complex networks.
AB  - Complex networks have acquired a great popularity in recent years, since the
      graph representation of many natural, social, and technological systems is often
      very helpful to characterize and model their phenomenology. Additionally, the
      mathematical tools of statistical physics have proven to be particularly suitable
      for studying and understanding complex networks. Nevertheless, an important
      obstacle to this theoretical approach is still represented by the difficulties to
      draw parallelisms between network science and more traditional aspects of
      statistical physics. In this paper, we explore the relation between complex
      networks and a well known topic of statistical physics: renormalization. A
      general method to analyze renormalization flows of complex networks is
      introduced. The method can be applied to study any suitable renormalization
      transformation. Finite-size scaling can be performed on computer-generated
      networks in order to classify them in universality classes. We also present
      applications of the method on real networks.

PMID- 19391804
TI  - Complex-anisotropy-induced pattern formation in bistable media.
AB  - A construct of anisotropy in bistable media is adopted to characterize the
      effects of anisotropy on pattern formation by means of anisotropic line tension.
      A velocity curvature relation is further derived to account for the anisotropic
      wave propagations. Stability analysis of transverse perturbations indicates that
      a sufficiently strong complex anisotropy can induce dynamical instabilities and
      even lead to a breakup of the wave patterns. Numerical simulations show that
      complex anisotropy can induce rich spatiotemporal behaviors in bistable media.
      The results of analysis and simulations demonstrate that this method successfully
      incorporates complex anisotropy into the reaction diffusion model and has general
      significance.

PMID- 19391805
TI  - Social network reciprocity as a phase transition in evolutionary cooperation.
AB  - In evolutionary dynamics the understanding of cooperative phenomena in natural
      and social systems has been the subject of intense research during decades. We
      focus attention here on the so-called "lattice reciprocity" mechanisms that
      enhance evolutionary survival of the cooperative phenotype in the prisoner's
      dilemma game when the population of Darwinian replicators interact through a
      fixed network of social contacts. Exact results on a "dipole model" are
      presented, along with a mean-field analysis as well as results from extensive
      numerical Monte Carlo simulations. The theoretical framework used is that of
      standard statistical mechanics of macroscopic systems, but with no energy
      considerations. We illustrate the power of this perspective on social modeling,
      by consistently interpreting the onset of lattice reciprocity as a
      thermodynamical phase transition that, moreover, cannot be captured by a purely
      mean-field approach.

PMID- 19391806
TI  - Feedback mechanism in network dynamics with preferential flow.
AB  - We study complex systems or networks in which each node holds an internal
      dynamics and interacts with other nodes through some kinds of topologies.
      Collective behavior with dynamical fluctuations is analyzed in complex systems.
      The dynamical fluctuations of a node can be divided into two parts: one is the
      internal dynamical fluctuation of the node and the other is the external
      dynamical fluctuation caused by other nodes. Based on a theoretical analysis, a
      hidden feedback mechanism is identified in complex systems, which is illustrated
      in a macroeconomic network and in a city-population network. Furthermore, we
      study the effect of the topology of the networks on the feedback mechanism. The
      feedback mechanism is preserved for hub nodes in the networks with a scale-free
      topology as well as in the networks with an evolving topology. By the hidden
      feedback mechanism, the observation data can be utilized to judge directly
      whether the system of each node is with positive feedback or with negative
      feedback even without knowing its dynamical model.

PMID- 19391807
TI  - Approximations on the Peano river network: application of the Horton-Strahler
      hierarchy to the case of low connections.
AB  - A network analysis is used to investigate the low connections of natural river
      channels. At the basin scale, the river networks are analyzed according to the
      Horton-Strahler hierarchy. We propose a quantitative criterion for the average
      junction degree as a function of a fixed hierarchical order of the network and
      independent of the usual scaling laws. The numerical results of this analysis are
      compared with exact results of the Peano river network, showing differences of
      the order of 10(-3). This aspect is especially relevant for the characterization
      of transport and diffusion processes at the basin scale.

PMID- 19391808
TI  - Dynamics of reaction-diffusion systems in a subdiffusive regime.
AB  - In this paper, we examine the dynamics of reaction-diffusion systems with
      fractional time derivatives. It is shown that in these conditions diffusion is
      anomalous, in the sense that the mean-square displacement r2 approximately
      tgamma, where gamma<1, a situation known as subdiffusion. We study the conditions
      for the appearance of a diffusion-driven instability and show that the
      restrictive conditions for a Turing instability are relaxed. This implies that
      systems whose kinetics are not of the activator-inhibitor kind can have a Turing
      instability and a modulated final state. We demonstrate our results with
      numerical calculations in two dimensions using a generic Turing model.

PMID- 19391809
TI  - Self-organized pacemakers and bistability of pulses in an excitable medium.
AB  - Pattern formation in an excitable medium described by a three-component reaction
      diffusion system is investigated. Our focus is on stable self-organized
      pacemakers which give rise to spatially extended target patterns. Bistability of
      pulse solutions in the excitable regime is also reported, and interactions of the
      different pulses with each other and the pacemaker are studied. Self-organized
      pacemakers are created by a suitable perturbation from the steady state or
      through interaction of pulses. Bound states of one-dimensional pacemakers and
      phase flips are also observed.

PMID- 19391810
TI  - Reinforced communication and social navigation generate groups in model networks.
AB  - To investigate the role of information flow in group formation, we introduce a
      model of communication and social navigation. We let agents gather information in
      an idealized network society and demonstrate that heterogeneous groups can evolve
      without presuming that individuals have different interests. In our scenario,
      individuals' access to global information is constrained by local communication
      with the nearest neighbors on a dynamic network. The result is reinforced
      interests among like-minded agents in modular networks; the flow of information
      works as a glue that keeps individuals together. The model explains group
      formation in terms of limited information access and highlights global
      broadcasting of information as a way to counterbalance this fragmentation. To
      illustrate how the information constraints imposed by the communication structure
      affects future development of real-world systems, we extrapolate dynamics from
      the topology of four social networks.

PMID- 19391811
TI  - Optimal weighting scheme for suppressing cascades and traffic congestion in
      complex networks.
AB  - This paper is motivated by the following two related problems in complex
      networks: (i) control of cascading failures and (ii) mitigation of traffic
      congestion. Both problems are of significant recent interest as they address,
      respectively, the security of and efficient information transmission on complex
      networks. Taking into account typical features of load distribution and weights
      in real-world networks, we have discovered an optimal solution to both problems.
      In particular, we shall provide numerical evidence and theoretical analysis that,
      by choosing a proper weighting parameter, a maximum level of robustness against
      cascades and traffic congestion can be achieved, which practically rids the
      network of occurrences of the catastrophic dynamics.

PMID- 19391812
TI  - Consensus of self-driven agents with avoidance of collisions.
AB  - In recent years, many efforts have been addressed on collision avoidance of
      collectively moving agents. In this paper, we propose a modified version of the
      Vicsek model with adaptive speed, which can guarantee the absence of collisions.
      However, this strategy leads to an aggregated state with slowly moving agents. We
      therefore further add a certain repulsion, which results in both faster consensus
      and longer safe distance among agents, and thus provides a powerful mechanism for
      collective motions in biological and technological multiagent systems.

PMID- 19391813
TI  - Implementation of glider guns in the light-sensitive Belousov-Zhabotinsky medium.
AB  - In cellular automata models a glider gun is an oscillating pattern of
      nonquiescent states that periodically emits traveling localizations (gliders).
      The glider streams can be combined to construct functionally complete systems of
      logical gates and thus realize universal computation. The glider gun is the only
      means of ensuring the negation operation without additional external input and
      therefore is an essential component of a collision-based computing circuit. We
      demonstrate the existence of glider-gun-like structures in both experimental and
      numerical studies of an excitable chemical system-the light-sensitive Belousov
      Zhabotinsky reaction. These discoveries could provide the basis for future
      designs of collision-based reaction-diffusion computers.

PMID- 19391814
TI  - Complexity measures from interaction structures.
AB  - We evaluate information-theoretic quantities that quantify complexity in terms of
      kth-order statistical dependences that cannot be reduced to interactions among k
      1 random variables. Using symbolic dynamics of coupled maps and cellular automata
      as model systems, we demonstrate that these measures are able to identify complex
      dynamical regimes.

PMID- 19391815
TI  - Threshold effect with stochastic fluctuation in bacteria-colony-like
      proliferation dynamics as analyzed through a comparative study of reaction
      diffusion equations and cellular automata.
AB  - We report a comparative study on pattern formation between the methods of
      cellular automata (CA) and reaction-diffusion equations (RD) applying to a
      morphology of bacterial colony formation. To do so, we began the study with
      setting an extremely simple model, which was designed to realize autocatalytic
      proliferation of bacteria (denoted as X ) fed with nutrition (N) and their
      inactive state (prespore state) P1 due to starvation: X+N-->2X and X-->P1,
      respectively. It was found numerically that while the CA could successfully
      generate rich patterns ranging from the circular fat structure to the viscous
      finger-like complicated one, the naive RD reproduced only the circular pattern
      but failed to give a finger structure. Augmenting the RD equations by adding two
      physical factors, (i) a threshold effect in the dynamics of X+N-->2X (breaking
      the continuity limit of RD) and (ii) internal noise with onset threshold
      (breaking the inherent symmetry of RD), we have found that the viscous-finger
      like realistic patterns are indeed recovered by thus modified RD. This highlights
      the important difference between CA and RD, and at the same time, clarifies the
      necessary factors for the complicated patterns to emerge in such a surprisingly
      simple model system.

PMID- 19391816
TI  - Pattern selection in parametrically driven arrays of nonlinear resonators.
AB  - We study the problem of pattern selection in an array of parametrically driven
      nonlinear resonators with application to microelectromechanical and
      nanoelectromechanical systems, using an amplitude equation recently derived by
      Bromberg, Cross, and Lifshitz [Phys. Rev. E 73, 016214 (2006)]. We describe the
      transitions between standing-wave patterns of different wave numbers as the drive
      amplitude is varied either quasistatically, abruptly, or as a linear ramp in
      time. We find interesting hysteretic effects, which are confirmed by numerical
      integration of the original equations of motion of the interacting nonlinear
      resonators.

PMID- 19391817
TI  - Exact results for the Kuramoto model with a bimodal frequency distribution.
AB  - We analyze a large system of globally coupled phase oscillators whose natural
      frequencies are bimodally distributed. The dynamics of this system has been the
      subject of long-standing interest. In 1984 Kuramoto proposed several conjectures
      about its behavior; ten years later, Crawford obtained the first analytical
      results by means of a local center manifold calculation. Nevertheless, many
      questions have remained open, especially about the possibility of global
      bifurcations. Here we derive the system's stability diagram for the special case
      where the bimodal distribution consists of two equally weighted Lorentzians.
      Using an ansatz recently discovered by Ott and Antonsen, we show that in this
      case the infinite-dimensional problem reduces exactly to a flow in four
      dimensions. Depending on the parameters and initial conditions, the long-term
      dynamics evolves to one of three states: incoherence, where all the oscillators
      are desynchronized; partial synchrony, where a macroscopic group of phase-locked
      oscillators coexists with a sea of desynchronized ones; and a standing wave
      state, where two counter-rotating groups of phase-locked oscillators emerge.
      Analytical results are presented for the bifurcation boundaries between these
      states. Similar results are also obtained for the case in which the bimodal
      distribution is given by the sum of two Gaussians.

PMID- 19391818
TI  - Delocalization induced by nonlinearity in systems with disorder.
AB  - We study numerically the effects of nonlinearity on the Anderson localization in
      lattices with disorder in one and two dimensions. The obtained results show that
      at moderate strength of nonlinearity a spreading over the lattice in time takes
      place with an algebraic growth of number of populated sites Deltan proportional
      to tnu. This spreading continues up to a maximal dimensionless time scale t=10(9)
      reached in the numerical simulations. The numerical values of nu are found to be
      approximately 0.15-0.2 and 0.25 for the dimension d=1 and 2, respectively, being
      in a satisfactory agreement with the theoretical value d/(3d+2). During the
      computational times t<or=10(9) the localization is preserved below a certain
      critical value of nonlinearity. We also discuss the properties of the fidelity
      decay induced by a perturbation of nonlinear field.

PMID- 19391819
TI  - Bouncing ball problem: stability of the periodic modes.
AB  - Exploring all its ramifications, we give an overview of the simple yet
      fundamental bouncing ball problem, which consists of a ball bouncing vertically
      on a sinusoidally vibrating table under the action of gravity. The dynamics is
      modeled on the basis of a discrete map of difference equations, which numerically
      solved fully reveals a rich variety of nonlinear behaviors, encompassing
      irregular nonperiodic orbits, subharmonic and chaotic motions, chattering
      mechanisms, and also unbounded nonperiodic orbits. For periodic motions, the
      corresponding conditions for stability and bifurcation are determined from
      analytical considerations of a reduced map. Through numerical examples, it is
      shown that a slight change in the initial conditions makes the ball motion switch
      from periodic to chaotic orbits bounded by a velocity strip v=+/-Gamma(1-epsilon)
      , where Gamma is the nondimensionalized shaking acceleration and epsilon the
      coefficient of restitution which quantifies the amount of energy lost in the ball
      table collision.

PMID- 19391820
TI  - Defect development in a three-dimensional reaction-diffusion system with
      gradient.
AB  - The formation and development of spiral defects is one of the major causes of
      order-disorder transitions in spatiotemporal patterns. In this paper, line defect
      formation and development in a three-dimensional reaction-diffusion system with
      gradients of control parameters in the third dimension is investigated. The
      system can be considered as diffusively coupled two-dimensional spatiotemporal
      patterns with dissimilarities. We observed that under certain conditions, as the
      gradients are varied, ordered and disordered spatiotemporal patterns appear
      alternately and line defects of various configurations form. This scenario is
      found to be in qualitative agreement with the experimental findings in the
      Belousov-Zhabotinsky reaction. We thus demonstrate that the line defect which was
      usually expected in two-dimensional complex oscillatory media can also be
      generated from the reconciliation between the coupled simple spiral waves with
      dissimilarity.

PMID- 19391821
TI  - Routes to chaos and multiple time scale dynamics in broadband bandpass nonlinear
      delay electro-optic oscillators.
AB  - The response of a nonlinear optical oscillator subject to a delayed broadband
      bandpass filtering feedback is studied experimentally, numerically, and
      analytically. The oscillator loop is characterized by a high cutoff frequency
      with a response time tau approximately 10 ps and by a low cutoff frequency with a
      response time theta approximately 1 micros. Moreover, the optoelectronic feedback
      also consists of a significant delay tauD of the order of 100 ns. Depending on
      two key physical parameters, the loop gain beta and the nonlinearity operating
      point Phi, a large variety of multiple time scale regimes are reported, including
      slow or fast periodic oscillations with different waveforms, regular or chaotic
      breathers, slow time envelope dynamics, complex and irregular self-pulsing, and
      fully developed chaos. Many of these regimes are exhibiting new features that are
      absent in the classical first-order scalar nonlinear delay differential equations
      (DDEs), which differ in the modeling by the low cutoff only. Nearly all kinds of
      solutions are recovered numerically by a new class of integro-DDE (iDDE) that
      take into account both the high and low cutoff frequencies of the feedback loop.
      For moderate feedback gain, asymptotic solutions are determined analytically by
      taking advantage of the relative values of the time constants tau, theta, and
      tauD. We confirm the experimental observation of two distinct routes to
      oscillatory instabilities depending on the value of Phi. One route is reminiscent
      of the square wave oscillations of the classical first-order DDE, but the other
      route is quite different and allows richer wave forms. For higher feedback gain,
      these two distinct regimes merge leading to complex nonperiodic regimes that
      still need to be explored analytically and numerically. Finally, we investigate
      the theoretical limits of our iDDE model by experimentally exploring phenomena at
      extreme physical parameter setting, namely, high-frequency locking at strong
      feedback gain or pulse packages for very large delays. The large variety of
      oscillatory regimes of our broadband bandpass delay electro-optic oscillator is
      attractive for applications requiring rich optical pulse sources with different
      frequencies and/or wave forms (chaos-based communications, random number
      generation, chaos computing, and generation of stable multiple GHz frequency
      oscillations).

PMID- 19391822
TI  - Compactons and chaos in strongly nonlinear lattices.
AB  - We study localized traveling waves and chaotic states in strongly nonlinear one
      dimensional Hamiltonian lattices. We show that the solitary waves are
      superexponentially localized and present an accurate numerical method allowing
      one to find them for an arbitrary nonlinearity index. Compactons evolve from
      rather general initially localized perturbations and collide nearly elastically.
      Nevertheless, on a long time scale for finite lattices an extensive chaotic state
      is generally observed. Because of the system's scaling, these dynamical
      properties are valid for any energy.

PMID- 19391823
TI  - Leader-laggard relationship of chaos synchronization in mutually coupled vertical
      cavity surface-emitting lasers with time delay.
AB  - We experimentally and numerically observe synchronization of chaos in two
      mutually coupled vertical-cavity surface-emitting lasers (VCSELs) with time
      delay. We observe in-phase and antiphase synchronization of polarization-resolved
      chaotic temporal wave forms under the condition of wavelength matching. We
      investigate leader-laggard relationship between two chaotic wave forms of
      mutually coupled VCSELs and find that the laser with longer wavelength becomes
      the leader.

PMID- 19391824
TI  - Universal spectral correlations in orthogonal-unitary and symplectic-unitary
      crossover ensembles of random matrices.
AB  - Orthogonal-unitary and symplectic-unitary crossover ensembles of random matrices
      are relevant in many contexts, especially in the study of time reversal symmetry
      breaking in quantum chaotic systems. Using skew-orthogonal polynomials we show
      that the same generic form of n-level correlation functions are obtained for the
      Jacobi family of crossover ensembles, including the Laguerre and Gaussian cases.
      For large matrices we find universal forms of unfolded correlation functions when
      expressed in terms of a rescaled transition parameter with arbitrary initial
      level density.

PMID- 19391825
TI  - Thermal effects on chaotic directed transport.
AB  - We study a chaotic ratchet system under the influence of a thermal environment.
      By direct integration of the Lindblad equation we are able to analyze its
      behavior for a wide range of couplings with the environment, and for different
      finite temperatures. We observe that the enhancement of the classical and quantum
      currents due to temperature depend strongly on the specific properties of the
      system. This makes it difficult to extract universal behaviors. We have also
      found that there is an analogy between the effects of the classical thermal noise
      and those of the finite h size. These results open many possibilities for their
      testing and implementation in kicked Bose-Einstein condensates and cold atoms
      experiments.

PMID- 19391826
TI  - Directed transport in a spatially periodic harmonic potential under periodic
      nonbiased forcing.
AB  - Transport of a particle in a spatially periodic harmonic potential under the
      influence of a slowly time-dependent unbiased periodic external force is studied.
      The equations of motion are the same as in the problem of a slowly forced
      nonlinear pendulum. Using methods of the adiabatic perturbation theory we show
      that for a periodic external force of a general kind the system demonstrates
      directed (ratchet) transport in the chaotic domain on very long time intervals
      and obtain a formula for the average velocity of this transport. Two cases are
      studied: The case of the external force of small amplitude, and the case of the
      external force with amplitude of order one. The obtained formulas can also be
      used in case of a nonharmonic periodic potential.

PMID- 19391827
TI  - Dynamical and statistical properties of high-temperature self-propagating fronts:
      an experimental study.
AB  - We present a detailed experimental study of high-temperature self-propagating
      fronts using image processing techniques. The intrinsic features of the wave
      propagation are investigated as a function of the combustion temperature TC for a
      model system made of titanium and silicon powders. Different front behavior is
      realized by changing the molar ratio x of the mixture Ti+xSi. Outside the range
      x=[0.3,1.5], no thermal front is propagating while inside, three regimes are
      observed: steady-state combustion which is characterized by a flat front
      propagating at constant velocity and two unsteady regimes. The combustion
      temperature (or the corresponding ratio x) is thus playing the role of
      bifurcation parameter leading from stationary state to complex behavior. In the
      titanium-rich mixture, the position of the front oscillates and hot spots
      propagate along the external border of the sample. At lower amounts of Ti,
      localized bright regions appear randomly and deform the front profile. The
      associated dynamical behavior is a relay-race mechanism which becomes more
      pronounced close to the combustion limit. Methods are developed to characterize
      the structural and dynamical properties of thermal waves near instabilities, with
      a special emphasis on the statistical aspects. It is clearly demonstrated that
      the mesoscopic scale phenomena interfere significantly with the macroscopic
      behavior. The experiments reveal front behaviors that cannot be described using
      the usual macroscopic theories.

PMID- 19391828
TI  - Chaotic scattering in a molecular system.
AB  - We study the classical dynamics of bound state and scattering trajectories of the
      chlorine atom interacting with the HO molecule using a two-dimensional model in
      which the HO bond length is held fixed. The bound state system forms the HOCl
      molecule and at low energies is predominantly integrable. Below dissociation a
      number of bifurcations are observed, most notably a series of saddle-center
      bifurcations related to a 2:1 and at higher energies 3:1 resonance between bend
      and stretch motions. At energies above dissociation the classical phase space
      becomes dominated by a homoclinic tangle which induces a fractal distribution of
      singularities in all scattering functions. The structure of the homoclinic tangle
      is examined directly using Poincare surfaces of section as well as indirectly
      through its influence on the time delay of the scattered chlorine atom and the
      angular momentum of the scattered HO molecule.

PMID- 19391829
TI  - Limit-cycle oscillation of an elastic filament and caterpillar motion.
AB  - Soft biological materials can exhibit various active motion such as limit-cycle
      oscillation. The limit-cycle oscillation of active matter might be used for a
      mechanism of locomotion. We propose a simple model of an active elastic chain as
      an extension of the van der Pol equation. The uniform state is unstable, and
      exhibits a limit cycle of breathing motion. If the breathing motion is mirror
      symmetric, the elastic chain does not move as a whole. However, the breathing
      motion becomes a caterpillar motion and a unidirectional motion is induced, if an
      additional heterogeneity is involved or the chain is set on a spatially periodic
      sawtooth potential. We also analyze the model equation with coupled mode
      equations, and try to understand the bifurcation to the collective oscillation
      and the directional motion.

PMID- 19391830
TI  - Exploring partial control of chaotic systems.
AB  - In this paper we make a thorough exploration of the technique of partial control
      of chaotic systems. This control technique allows one to keep the trajectories of
      a dynamical system close to a chaotic saddle even if the control applied is
      smaller than the effects of environmental noise in the system, provided that the
      chaotic saddle is due to the existence of a horseshoelike mapping in phase space.
      We state this here in a mathematically precise way using the Conley-Moser
      conditions, and we prove that they imply that our partial control strategy can be
      applied. We also give an upper bound of the control-noise ratio needed to achieve
      this goal, and we describe how this technique can be applied for large noise
      values. Finally, we study in detail the effect of imperfect targeting in our
      control technique. All these results are illustrated numerically with the
      paradigmatic Henon map.

PMID- 19391831
TI  - Liberation of a pinned spiral wave by a single stimulus in excitable media.
AB  - The unpinning of a spiral wave from an anatomic obstacle by the application of a
      single stimulus near the core of the rotating wave was studied experimentally in
      a cell culture of cardiomyocyte monolayers as well as by computer simulations. It
      is shown that, with suitable positioning and timing, a single stimulus is
      sufficient for the successful unpinning of a pinned spiral wave. Successful
      unpinning is achieved when two conditions are fulfilled: (1) The stimulus is
      delivered in the vulnerable window of the rotating wave, and (2) the stimulus is
      delivered in a spatial zone in proximity to the obstacle, where the shape of the
      zone is defined by the phase of the anchored spiral wave. Two different scenarios
      for successful unpinning are discussed, which are distinguished by the distance
      to the stimuli applied to the obstacle.

PMID- 19391832
TI  - Networks on the edge of chaos: global feedback control of turbulence in
      oscillator networks.
AB  - Random networks of coupled phase oscillators with phase shifts in the interaction
      functions are considered. In such systems, extensive chaos (turbulence) is
      observed in a wide range of parameters. We show that, by introducing global
      feedback, the turbulence can be suppressed and a transition to synchronous
      oscillations can be induced. Our attention is focused on the transition scenario
      and the properties of patterns, including intermittent turbulence, which are
      found at the edge of chaos. The emerging coherent patterns represent various self
      organized active (sub)networks whose size and behavior can be controlled.

PMID- 19391833
TI  - Coherent wave patterns sustained by a localized inhomogeneity in an excitable
      medium.
AB  - The influence of a localized inhomogeneity (oscillatory or stationary) on
      spatiotemporal chaotic state in an excitable reaction-diffusion system is
      investigated. We find that various coherent wave patterns, such as spiral waves
      (including multiarmed) and target wave patterns are able to be created by the
      inhomogeneity from the chaotic state. Due to the growth of these coherent wave
      patterns, the previously existing turbulent waves in the absence of inhomogeneity
      are suppressed. At last, the whole system is entrained by the coherent wave
      patterns. Closer investigations indicate that the possible mechanisms underlying
      the inhomogeneity sustained coherent wave patterns seem quite different for
      oscillatory and stationary inhomogeneities.

PMID- 19391834
TI  - Comparison of Faxen's correction for a microsphere translating or rotating near a
      surface.
AB  - Boundary walls in microfluidic devices have a strong influence on the fluid flow
      and drag forces on moving objects. The Stokes drag force acting on a sphere
      translating in the fluid is increased by the presence of a neighboring wall by a
      factor given by Faxen's correction. A similar increase in the rotational drag is
      expected when spinning close to a wall. We use optical tweezers to confirm the
      translational drag correction and report the hitherto unmeasured rotational
      equivalent. We find that the corrections for the rotational motion is only
      required for particle-wall separations an order of magnitude shorter than that
      for the translational cases. These results are particularly significant in the
      use of optical tweezers for measuring viscosity on a picolitre scale.

PMID- 19391835
TI  - Nanoparticle assembly via the dewetting of patterned thin metal lines:
      understanding the instability mechanisms.
AB  - Nanosecond pulsed laser heating was used to control the assembly of spatially
      correlated nanoparticles from lithographically patterned pseudo-one-dimensional
      nickel lines. The evolution of the nickel line instabilities and nanoparticle
      formation with a correlated size and spacing was observed after a series of laser
      pulses. To understand the instabilities that direct the nanoparticle assembly, we
      have carried out nonlinear time-dependent simulations and linear stability
      analysis based on a simple hydrodynamic model. We find that the simulated time
      scales and length scales agree well with the experimental results. Interestingly,
      in both experiments and simulations, the instabilities associated with the line
      edge, and with the surface perturbation-driven mechanism, are found to result in
      similar particle sizes and spacings.

PMID- 19391836
TI  - Intermittency and scale-dependent statistics in fully developed turbulence.
AB  - Fully developed homogeneous isotropic turbulent fields, computed by direct
      numerical simulation, are compared to divergence-free random fields having the
      same energy spectrum and either the same helicity spectrum as that of the
      turbulent data, or vanishing helicity. We show that the scale-dependent velocity
      flatness quantifies the spatial variability of the energy spectrum. The flatness
      exhibits a substantial increase at small scales for the turbulent field, but
      remains constant for the random fields. A diagnostic, the scale-dependent
      helicity, is proposed to quantify the geometrical statistics of the flow, which
      shows that only the turbulent flow is intermittent. Finally, statistical scale
      dependent analyses of both Eulerian and Lagrangian accelerations confirm the
      inherently different dynamics of turbulent and random flows.

PMID- 19391837
TI  - Helicity cascades in rotating turbulence.
AB  - The effect of helicity (velocity-vorticity correlations) is studied in direct
      numerical simulations of rotating turbulence down to Rossby numbers of 0.02. The
      results suggest that the presence of net helicity plays an important role in the
      dynamics of the flow. In particular, at small Rossby number, the energy cascades
      to large scales, as expected, but helicity then can dominate the cascade to small
      scales. A phenomenological interpretation in terms of a direct cascade of
      helicity slowed down by wave-eddy interactions leads to the prediction of non
      Kolmogorovian inertial indices for the small-scale energy and helicity spectra.

PMID- 19391838
TI  - Effects of wall roughness on flow in nanochannels.
AB  - Nonequilibrium molecular dynamics simulation is applied to investigate the effect
      of periodic wall roughness on the flow of liquid argon through krypton
      nanochannels. The effect of the length of a rectangular protrusion on the flow is
      investigated and compared to the case of nanochannels with flat walls. The
      results show a clear trapping of fluid atoms inside the rectangular cavities that
      are formed between successive protrusions. The size of the cavities affects the
      potential energy map and, consequently, fluid atom localization. This
      localization results in a reduction of velocity values inside the cavities, as
      well as a reduction of the slip length near the rough wall.

PMID- 19391839
TI  - Measurements of the thermal dissipation field in turbulent Rayleigh-Benard
      convection.
AB  - A systematic study of the thermal dissipation field and its statistical
      properties is carried out in turbulent Rayleigh-Benard convection. A local
      temperature gradient probe consisting of four identical thermistors is made to
      measure the normalized thermal dissipation rate epsilonN(r) in two convection
      cells filled with water. The measurements are conducted over varying Rayleigh
      numbers Ra (8.9x10(8)<approximately Ra<approximately 9.3x10(9)) and spatial
      positions r across the entire cell. It is found that epsilonN(r) contains two
      contributions; one is generated by thermal plumes, present mainly in the plume
      dominated bulk region, and decreases with increasing Ra. The other contribution
      comes from the mean temperature gradient, being concentrated in the thermal
      boundary layers, and increases with Ra. The experiment provides a complete
      physical picture about the thermal dissipation field and its statistical
      properties in turbulent convection.

PMID- 19391840
TI  - Coalescence of low-viscosity fluids in air.
AB  - An electrical method is used to study the early stages of coalescence of two low
      viscosity drops. A drop of aqueous NaCl solution is suspended in air above a
      second drop of the same solution, which is grown until the drops touch. At that
      point a rapidly widening bridge forms between them. By measuring the resistance
      and capacitance of the system during this coalescence event, one can obtain
      information about the time dependence of the characteristic bridge radius and its
      characteristic height. At early times, a new asymptotic regime is observed that
      is inconsistent with previous theoretical predictions. The measurements at
      several drop radii and approach velocities are consistent with a model in which
      the two liquids coalesce with a slightly deformed interface.

PMID- 19391841
TI  - Convective stability of multicomponent fluids in the thermogravitational column.
AB  - A comprehensive linear stability analysis of convection in the
      thermogravitational column is first performed for multicomponent fluids. Two
      types of perturbations are investigated: Longitudinal waves propagating in
      vertical direction of the column and transversal waves propagating perpendicular
      to the vertical axis and temperature gradient. The stability problems are reduced
      to those without cross-diffusion effect by a special transformation. The
      calculations are performed for binary and ternary mixtures by the Galerkin
      method. It is found that in binary fluids, the onset of longitudinal instability
      can be monotonic or oscillatory depending on the separation ratio, which
      characterizes the Soret effect. The difference between stability characteristics
      of binary and ternary fluids is associated with different diffusion times of
      components in a ternary system. It is shown that the mechanism of transversal
      instability is related to the unstable density stratification in the column (in
      total or due to individual components). The unstable stratification can only be
      realized in fluids with negative Soret effect. The analogue of exchange of
      stabilities principle for a plane column with a multicomponent fluid is proved.
      The obtained results indicate that the thermogravitational column can be used for
      measuring diffusion and thermal diffusion coefficients in ternary and higher
      mixtures with one or several components having negative Soret effect.

PMID- 19391842
TI  - ac-Field-induced fluid pumping in microsystems with asymmetric temperature
      gradients.
AB  - We present two different designs of electrohydrodynamic micropumps for
      microfluidic systems. The micropumps have no movable parts, and their simple
      design allows for fabrication by microsystems technology. The pumps are operated
      by ac voltages from 1 to 60 V and were tested with aqueous solutions in the
      conductivity range of 1-112 mS m(-1). The pump effect is induced by an ac
      electric field across a fluid medium with an inhomogeneous temperature
      distribution. It is constant over a wide range of the ac field frequency with a
      conductivity-dependent drop-off at high frequencies. The temperature-dependent
      conductivity and permittivity distributions in the fluid induce space charges
      that interact with the electric field and induce fluid motion. The temperature
      distribution can be generated either by Joule heating in the medium or by
      external heating. We present experimental results obtained with two prototypes
      featuring Joule heating and external heating by a heating filament. Experimental
      and numerical results are compared with an analytical model.

PMID- 19391843
TI  - Resurgence flows in porous media.
AB  - Porous media with resurgences can be described by a double structure, namely, a
      continuous porous medium and capillaries with impermeable walls which relate
      distant points of the continuous medium. The resurgences can be either punctual
      or extended. The equations for flow in such media are derived; some general
      properties of the resulting system, which involves nonlocal aspects, are deduced.
      A "dilute" approximation is detailed for punctual resurgences in two-dimensional
      media and is illustrated by a few examples.

PMID- 19391844
TI  - Mixing at the external boundary of a submerged turbulent jet.
AB  - We study experimentally and theoretically mixing at the external boundary of a
      submerged turbulent jet. In the experimental study we use particle image
      velocimetry and an image processing technique based on the analysis of the
      intensity of the Mie scattering to determine the spatial distribution of tracer
      particles. An air jet is seeded with the incense smoke particles, which are
      characterized by a large Schmidt number and a small Stokes number. We determine
      the spatial distributions of the jet fluid characterized by a high concentration
      of the particles and of the ambient fluid characterized by a low concentration of
      the tracer particles. In the data analysis we use two approaches, whereby one
      approach is based on the measured phase function for the study of the mixed state
      of two fluids. The other approach is based on the analysis of the two-point
      second-order correlation function of the particle number density fluctuations
      generated by tangling of the gradient of the mean particle number density by the
      turbulent velocity field. This gradient is formed at the external boundary of a
      submerged turbulent jet. We demonstrate that probability density function of the
      phase function of a jet fluid penetrating into an external flow and the two-point
      second-order correlation function of the particle number density do not have
      universal scaling and cannot be described by a power-law function. The
      theoretical predictions made in this study are in qualitative agreement with the
      obtained experimental results.

PMID- 19391845
TI  - Surface effects on friction-induced fluid heating in nanochannel flows.
AB  - We investigate the mechanism of friction-induced fluid heating under the
      influence of surfaces. The temperature distributions of liquid argon and helium
      in nanoscale Poiseuille flows are studied through molecular dynamics simulations.
      It is found that the fluid heating is mainly caused by the viscous friction in
      the fluid when the external force is small and there is no slip at the fluid
      solid interface. When the external force is larger than the fluid-surface binding
      force, the friction at the fluid-solid interface dominates over the internal
      friction of the fluid and is the major contribution to fluid heating. An
      asymmetric temperature gradient in the fluid is developed in the case of
      nonidentical walls and the general temperature gradient may change sign as the
      dominant heating factor changes from internal to interfacial friction with
      increasing external force. The effect of temperature on the fluid heating is also
      discussed.

PMID- 19391846
TI  - Influence of contact angle on slow evaporation in two-dimensional porous media.
AB  - We study numerically the influence of contact angle on slow evaporation in two
      dimensional model porous media. For sufficiently low contact angles, the drying
      pattern is fractal and can be predicted by a simple model combining the invasion
      percolation model with the computation of the diffusive transport in the gas
      phase. The overall drying time is minimum in this regime and is independent of
      contact angle over a large range of contact angles up to the beginning of a
      transition zone. As the contact angle increases in the transition region, the
      cooperative smoothing mechanisms of the interface become important and the width
      of the liquid gas interface fingers that form during the evaporation process
      increases. The mean overall drying time increases in the transition region up to
      an upper bound which is reached at a critical contact angle thetac. The increase
      in the drying time in the transition region is explained in relation with the
      diffusional screening phenomenon associated with the Laplace equation governing
      the vapor transport in the gas phase. Above thetac the drying pattern is
      characterized by a flat traveling front and the mean overall drying time becomes
      independent of the contact angle. Drying time fluctuations are studied and are
      found to be important below thetac, i.e., when the pattern is fractal. The
      fluctuations are of the same order of magnitude regardless of the value of
      contact angle in this range. The fluctuations are found to die out abruptly at
      thetac as the liquid gas interface becomes a flat front.

PMID- 19391847
TI  - Viscous effects on Bragg scattering of water waves by an array of piles.
AB  - We examine the effects of viscous damping in the boundary layers on the Bragg
      resonance of surface water waves by a two-dimensional array of vertical
      cylinders. For cylinders of small radius relative to the wavelength, we first
      derive an effective boundary condition for the radial derivative of the velocity
      potential to account for the viscous forces. Coupled-mode equations are then
      rederived by an asymptotic method for the envelopes of multiply resonated waves
      inside the array. Effects of viscosity on band gaps and scattering coefficients
      due to a plane incident wave are examined analytically for an infinitely long
      array of finite width surrounded by open water. For normal incidence the envelope
      physics is one dimensional. The transmission and reflection properties are
      studied first. Oblique incidence can in principle excite several wave trains in
      different directions. Explicit solutions are given and discussed when there are
      only two wave trains inside the array. Results are compared with recent theories
      where viscosity is not taken into account. The asymptotic theory can be modified
      for two-dimensional sound scattering by a cylinder array.

PMID- 19391848
TI  - Convection in binary fluid mixtures with modulated heating.
AB  - The response behavior of strongly nonlinear binary fluid convection to temporal
      modulation of the heating is investigated for the case of a negative Soret
      coupling between temperature and concentration gradients. Finite difference
      numerical simulations are performed for ethanol-water parameters subject to
      realistic boundary conditions. Traveling waves with modulated amplitudes and
      phase velocities, subharmonic standing waves, and synchronously modulated
      patterns with fixed spatial phase are found as stable solutions. The hysteretic
      transitions between subcritical traveling and standing waves that coexist
      bistably with the quiescent fluid state are investigated. Various diagnostic
      analysis tools are used to elucidate the complex spatiotemporal and bifurcation
      properties that are ultimately caused by nonlinear advection and mixing of
      concentration being very strong.

PMID- 19391849
TI  - Time-correlation functions and transport coefficients of two-dimensional Yukawa
      liquids.
AB  - The existence of coefficients for diffusion, viscosity, and thermal conductivity
      is examined for two-dimensional (2D) liquids. Equilibrium molecular dynamics
      simulations are performed using a Yukawa potential and the long-time behavior of
      autocorrelation functions is tested. Advances reported here as compared to
      previous 2D Yukawa liquid simulations include an assessment of the thermal
      conductivity, using a larger system size to allow meaningful examination of
      longer times, and development of improved analysis methods. We find that the
      transport coefficient exists for diffusion at high temperature and viscosity at
      low temperature, but not in the opposite limits. The thermal conductivity
      coefficient does not appear to exist at high temperature. Further advances in
      computing power could improve these assessments by allowing even larger system
      sizes and longer time series.

PMID- 19391851
TI  - Application of Doppler spectroscopy in H2 to the prediction of experimental
      D(d,n)3He reaction rates in an inertial electrostatic confinement device.
AB  - In our previous paper, we developed an optical measurement for absolute densities
      of fast (tens of keV) H ions in an abnormal hollow cathode discharge of hydrogen
      in the units to tens of mTorr pressure range. We apply this method to a
      cylindrically symmetric inertial electrostatic confinement (IEC) discharge of
      hydrogen using the Doppler spectrum of Halpha. We predict neutron production
      rates for an equivalent discharge of deuterium and compare these with
      experimental values under the separate conditions of constant deuterium gas
      pressure (approximately 6 mTorr) and voltage (30 kV). Our predictions capture the
      variation of production rates with dc current (10-50 mA) and agree with
      experiment to within an order of magnitude. The applicability of this diagnostic
      to the cylindrical IEC discharge is thus demonstrated, with our results
      supporting the theory that the discharge is dominated by energetic neutrals
      emerging from the cathode apertures.

PMID- 19391850
TI  - Intensity and polarization of laser-induced fluorescence due to forbidden
      excitation of He atoms immersed in an electric field in plasmas.
AB  - Laser-induced fluorescence (LIF) processes through the Stark and electric
      quadrupole moment (QDP) transitions of HeI (2(1)S-->n1D-->2(1)P,n=3,4) have been
      investigated for reliable electric-field measurements in plasmas. A linear
      polarization model is formulated for various configurations of electric fields,
      magnetic fields, and laser polarization. To extend the model to higher-particle
      density plasmas we develop a rate-equation model involving a collisional
      disalignment term. Disalignment rates of n1D states, Rda, due to a collision with
      He gas were measured. Spatial distributions in intensity and polarization of LIF
      were observed in a discharge plasma. For n=3 with small Rda, the same electric
      field distribution in the sheath was obtained from either of the intensity ratios
      of the Stark to QDP component and the polarization, and the sheath potential
      agreed well with that by an electric probe. For n=4 with large Rda, the
      distribution was also correctly obtained from partially depolarized LIF wave
      forms by using the extended model. These results show that our extended model
      provides an accurate measurement of the electric field. The minimum detectable
      field strength was 80 V/cm for n=4. Application and limitations of the methods
      are discussed.

PMID- 19391852
TI  - Phase mixing of relativistically intense waves in a cold homogeneous plasma.
AB  - We report on spatiotemporal evolution of relativistically intense longitudinal
      electron plasma waves in a cold homogeneous plasma, using the physically
      appealing Dawson sheet model. Calculations presented here in the weakly
      relativistic limit clearly show that under very general initial conditions, a
      relativistic wave will always phase mix and eventually break at arbitrarily low
      amplitudes, in a time scale omegapetaumix approximately
      {3/64(omegape2delta3/c2k2)|Deltak/k|(|1+Deltak/k|)](1+1|1+Deltak/k|)}(-1). We
      have verified this scaling with respect to amplitude of perturbation delta and
      width of the spectrum (Deltakk) using numerical simulations. This result may be
      of relevance to ultrashort, ultraintense laser pulse-plasma interaction
      experiments where relativistically intense waves are excited.

PMID- 19391853
TI  - Selective nanoparticle heating: another form of nonequilibrium in dusty plasmas.
AB  - Nanoparticles produced in low-temperature plasmas (LTPs) are often found with
      crystalline structure, which suggests rather high temperatures during synthesis.
      This even applies to particles of high-melting-point materials, which is
      surprising, because the gas temperature in LTPs is often close to room
      temperature and particles may reside in the plasma only for a few milliseconds.
      In this paper, we present a numerical study of nanoparticle heating in plasmas
      through energetic surface reactions. We find that, under realistic plasma
      conditions, particle temperatures can exceed the gas temperature by many hundreds
      of kelvins. However, as the particle temperature is highly unsteady, it is more
      reasonable to consider particle temperature distribution functions. The
      dependence of the particle temperature distribution on particle size and particle
      density in a dusty LTP is discussed.

PMID- 19391854
TI  - Single dust-particle rotation in glow-discharge plasma.
AB  - Rotation of a single dust granule (spin) is investigated experimentally in a
      stratified glow discharge. We employ the technique of measurement of the angular
      velocity, which is based on coordinate tracing of the light scattered by a hollow
      transparent particle. The angular velocity measured in the experiment is about 1
      2 orders of magnitude higher than observed in previous experiments. We found that
      the angular velocity depends linearly on the discharge current. The mechanism of
      rotation of the granule is also described.

PMID- 19391855
TI  - Dressed-particle approach in the nonrelativistic classical limit.
AB  - For a nonrelativistic classical particle undergoing arbitrary oscillations in
      external fields, the generalized effective potential Psi is derived through
      calculating the nonlinear eigenfrequencies of the particle-field system.
      Specifically, the ponderomotive potential is extended to a nonlinear oscillator,
      resulting in multiple branches near the primary resonance. For a pair of particle
      natural frequencies in a beat resonance, Psi scales linearly with the internal
      actions and is analogous to the dipole potential for a two-level quantum system.
      Thus cold quantum particles and highly excited quasiclassical objects permit
      uniform manipulation tools, particularly, one-way walls.

PMID- 19391856
TI  - Coagulation of nanoparticles in a plasma.
AB  - Coagulation of nanoparticles in a low-pressure radio frequency plasma was studied
      by means of a detailed numerical model for the spatiotemporal evolution of the
      nanoparticle-plasma system. Simulation results indicate that the occurrence of
      coagulation to any significant degree in such systems requires the existence of
      two effects: first, gas-phase nucleation is not limited to a brief burst, but
      rather continues in regions that are sufficiently free of nanoparticles; and
      second, coagulation coefficients for collisions between neutral and negatively
      charged nanoparticles are enhanced by the image potential induced in the neutral
      particle. Accounting for these effects, coagulation is predicted to be dominated
      by coagulation between very small (approximately 1 or 2 nm in diameter) neutral
      particles and larger negatively charged particles that are trapped in the plasma.
      Coagulation ceases when the spreading of the nanoparticle cloud across the plasma
      quenches gas-phase nucleation.

PMID- 19391857
TI  - Electromagnetic tunneling in a sandwich structure containing single negative
      media.
AB  - In this paper, the electromagnetic (EM) tunneling phenomenon in a sandwich
      structure consisting of an mu-negative (MNG) medium, air, and an epsilon-negative
      (ENG) medium is investigated by means of the transfer-matrix method and microwave
      experiments. Both results demonstrate that by properly choosing parameters, EM
      waves can efficiently tunnel through a long distance over several hundreds times
      the length of the device. Unlike in the ENG-MNG slabs, the electric and the
      magnetic field of the tunneling mode is interestingly separated and localized at
      the interface of MNG-air and ENG-air, respectively. Therefore, this structure may
      be important for potential applications in wireless information and energy
      transmission, for its high efficiency, security, and health.

PMID- 19391858
TI  - Stability of particle rotation in a rotating electric field.
AB  - Depending on the parameters of a particle and of a host medium, a particle in a
      rotating electric field can rotate either in the direction of rotation of
      electric field or in the opposite direction. There exists a range of parameters
      where both regimes of rotation can be realized simultaneously. In this study we
      investigate stability of rotation regimes in the whole range of parameters. We
      determine the range of parameters where different modes of particle rotation are
      stable, the range of parameters where only one regime of rotation is stable and
      the range of parameters where both regimes of rotation are unstable. It is shown
      that if the mode of rotation is realized outside the domain of the existence of
      two regimes of rotation, then this rotation mode is stable. Consequently,
      unstable regimes can be realized only in the range of parameters where both modes
      of rotation can exist simultaneously. We suggest a simple algorithm for
      determining the range of stability through the parameters of the system which
      does not require calculating frequencies of particle rotation in each of the
      possible rotation regimes.

PMID- 19391859
TI  - Modulational instability of zone boundary mode and band edge modes in nonlinear
      diatomic lattices.
AB  - We analyze the modulational instability of the zone boundary mode (ZBM) and the
      band edge modes (BEMs) in a one-dimensional nonlinear diatomic lattice and obtain
      rigorous results. Some numerical calculations of modulational instability in
      these modes are presented. These results indicate that the modulational
      instability of the BEMs leads to excitation of the discrete breathers (DBs) in
      the band gap, while that of the ZBM leads to excitation of the DBs above the
      phonon band.

PMID- 19391860
TI  - Electromagnetic boundary and its realization with anisotropic metamaterial.
AB  - A set of boundary conditions requiring vanishing of the normal components of the
      D and B vectors at the boundary surface is introduced and labeled as that of DB
      boundary. Basic properties of the DB boundary are studied in this paper.
      Reflection of an arbitrary plane wave, incident with a complex propagation
      vector, is analyzed for the planar DB boundary. It is shown that waves polarized
      transverse electric (TE) and transverse magnetic (TM) with respect to the normal
      of the boundary are reflected as from respective perfect electric conductor and
      perfect magnetic conductor planes. The basic problem of current source above the
      planar DB boundary is solved by applying TE and TM decomposition for the source.
      Realization of the DB boundary in terms of an interface of uniaxially anisotropic
      metamaterial half-space with zero axial medium parameters is considered. It is
      also shown that such a medium with small axial parameters acts as a spatial
      filter for waves incident at the interface which could be used for narrowing the
      beam of a directive antenna. Application of DB boundary as an isotropic soft
      surface with low interaction between antenna apertures also appears possible.

PMID- 19391861
TI  - Multicomponent cnoidal waves in cascade quasisynchronous frequency conversion.
AB  - It is shown that cascade quasisynchronous frequency conversion due to quadratic
      nonlinearity can be described in terms of an effective cubic nonlinearity. This
      enables one to reduce a four-mode interaction problem to solving a system of two
      coupled nonlinear Schrodinger equations for the amplitudes of the waves
      participating in both nonlinear processes. Exact analytic solutions of the
      corresponding system are found in the form of multicomponent cnoidal waves with
      components expressed through a sum and a difference of two similar fundamental
      solutions of the Lame equation with shifted arguments. It is shown that solutions
      obtained in such a way enable one to optimize the conversion efficiency because
      of full coverage of the range of possible boundary conditions.

PMID- 19391862
TI  - Directional, nonpropagating, and polychromatic excitations in one-dimensional
      wave systems.
AB  - It has been demonstrated that, in a one-dimensional wave system, monochromatic
      waves may be generated which are completely localized to the region of excitation
      or which propagate in only one direction. We further the discussion of such
      nonpropagating and directional excitations and demonstrate that they can be
      extended to excitations of an arbitrary finite number of frequencies. Two
      techniques for mathematically constructing these excitations are discussed.
      Furthermore, the relation between nonpropagating excitations and nonscattering
      scatterers is discussed. The results presented here may be useful in the
      development of devices for one-dimensional and quasi-one-dimensional wave
      systems.

PMID- 19391863
TI  - Optical nanotrapping using cloaking metamaterial.
AB  - We study the electromagnetic behavior of spherical semishell structures that have
      cloaking material properties proposed by Pendry, Schurig, and Smith [Science 312,
      1780 (2006)]. We use three-dimensional full-wave time-harmonic field analysis to
      evaluate the field and dipolar force distribution produced by these structures in
      free-space under plane wave illumination. We show that the optical force in
      proximity to these structures is suitable for active and size-selective
      manipulation and trapping of neutral nanoscale particles.

PMID- 19391864
TI  - Maxwell's macroscopic equations, the energy-momentum postulates, and the Lorentz
      law of force.
AB  - We argue that the classical theory of electromagnetism is based on Maxwell's
      macroscopic equations, an energy postulate, a momentum postulate, and a
      generalized form of the Lorentz law of force. These seven postulates constitute
      the foundation of a complete and consistent theory, thus eliminating the need for
      actual (i.e., physical) models of polarization P and magnetization M , these
      being the distinguishing features of Maxwell's macroscopic equations. In the
      proposed formulation, P(r,t) and M(r,t) are arbitrary functions of space and
      time, their physical properties being embedded in the seven postulates of the
      theory. The postulates are self-consistent, comply with the requirements of the
      special theory of relativity, and satisfy the laws of conservation of energy,
      linear momentum, and angular momentum. One advantage of the proposed formulation
      is that it sidesteps the long-standing Abraham-Minkowski controversy surrounding
      the electromagnetic momentum inside a material medium by simply "assigning" the
      Abraham momentum density E(r,t)xH(r,t)/c2 to the electromagnetic field. This well
      defined momentum is thus taken to be universal as it does not depend on whether
      the field is propagating or evanescent, and whether or not the host medium is
      homogeneous, transparent, isotropic, dispersive, magnetic, linear, etc. In other
      words, the local and instantaneous momentum density is uniquely and unambiguously
      specified at each and every point of the material system in terms of the E and H
      fields residing at that point. Any variation with time of the total
      electromagnetic momentum of a closed system results in a force exerted on the
      material media within the system in accordance with the generalized Lorentz law.

PMID- 19391865
TI  - Stationary and pulsating dissipative light bullets from a collective variable
      approach.
AB  - A collective variable approach is used to map domains of existence for (3+1)
      dimensional spatiotemporal soliton solutions of a complex cubic-quintic Ginzburg
      Landau equation. A rich variety of evolution behaviors, which include stationary
      and pulsating dissipative soliton dynamics, is revealed. Comparisons between the
      results obtained by the semianalytical approach of collective variables, and
      those obtained by a purely numerical approach show good agreement for a wide
      range of equation parameters. This also demonstrates the relevance of the
      semianalytical method for a systematic search of stability domains for
      spatiotemporal solitons, leading to a dramatic reduction of the computation time.

PMID- 19391866
TI  - Determination of the effective constitutive parameters of bianisotropic
      metamaterials from reflection and transmission coefficients.
AB  - We propose a method to retrieve the effective constitutive parameters of a slab
      of bianisotropic metamaterial from reflection and transmission coefficients (or
      scattering parameters). In our retrieval method, only the scattering parameters
      in one propagation direction are used. Analytical inversion equations are derived
      in order to retrieve the effective parameters of the permittivity, permeability,
      and magnetoelectric coupling coefficient of the bianisotropic metamaterial. To
      demonstrate the validity of the method, we used it to retrieve the parameters of
      four different metamaterials, among which two were normal media without
      bianisotropy and the other two were bianisotropic media. In using our retrieval
      method, including bianisotropy, the intrinsic differences between a normal medium
      and a bianisotropic medium were illustrated clearly. Our simulation and retrieval
      results also corroborate the conclusions of the previously published literature.

PMID- 19391867
TI  - Nonlinear Fano-Feshbach resonances.
AB  - We study the wave scattering in an one-dimensional discrete system with two side
      coupled defects. Each of the defects exhibits the Fano resonance as a resonant
      suppression of transmission, i.e., resonant reflection. We demonstrate that the
      interaction between two Fano resonances may give rise to a birth of a very narrow
      resonance. This effect may be understood in terms of the overlapping resonances,
      as suggested by Feshbach [Ann. Phys. 5, 357 (1958)]. We consider two cases, when
      the defects are coupled either locally or nonlocally to the discrete array. In
      the latter case, a sharp asymmetric resonance appears with a large quality
      factor. We demonstrate that by introducing a nonlinearity at side-coupled defects
      a closed loop in the nonlinear transmission coefficient may appear, which results
      in bistable response.

PMID- 19391868
TI  - Boundary slip from the immersed boundary lattice Boltzmann models.
AB  - We report an interesting and important observation of the velocity fields from
      immersed boundary lattice Boltzmann methods (IB-LBM). The computed velocity
      profiles can deviate from theoretical predictions greatly even for very simple
      flow situations, both in the immersed boundary layer and the bulk region. A
      rigorous analysis of the IB-LBM simulated velocity for a symmetric shear flow is
      carried out, and the analytical solutions indicate a strong dependence of
      velocity on the relaxation parameter (kinetic viscosity). Also our simulations
      demonstrate that simply increasing the immersed boundary layer thickness is not
      an efficient approach to reduce such velocity discrepancy. We hope this work will
      bring the awareness of this essential issue to people using IB-LBM for various
      flow situations.

PMID- 19391869
TI  - Lattice Boltzmann equation for microscale gas flows of binary mixtures.
AB  - Modeling and simulating gas flows in and around microdevices are a challenging
      task in both science and engineering. In practical applications, a gas is usually
      a mixture made of different components. In this paper we propose a lattice
      Boltzmann equation (LBE) model for microscale flows of a binary mixture based on
      a recently developed LBE model for continuum mixtures [P. Asinari and L.-S. Luo,
      J. Comput. Phys. 227, 3878 (2008)]. A consistent boundary condition for gas-solid
      interactions is proposed and analyzed. The LBE is validated and compared with
      theoretical results or other reported data. The results show that the model can
      serve as a potential method for flows of binary mixture in the microscale.

PMID- 19391870
TI  - Generalized lattice Boltzmann equation with forcing term for computation of wall
      bounded turbulent flows.
AB  - In this paper, we present a framework based on the generalized lattice Boltzmann
      equation (GLBE) using multiple relaxation times with forcing term for eddy
      capturing simulation of wall-bounded turbulent flows. Due to its flexibility in
      using disparate relaxation times, the GLBE is well suited to maintaining
      numerical stability on coarser grids and in obtaining improved solution fidelity
      of near-wall turbulent fluctuations. The subgrid scale (SGS) turbulence effects
      are represented by the standard Smagorinsky eddy viscosity model, which is
      modified by using the van Driest wall-damping function to account for reduction
      of turbulent length scales near walls. In order to be able to simulate a wider
      class of problems, we introduce forcing terms, which can represent the effects of
      general nonuniform forms of forces, in the natural moment space of the GLBE.
      Expressions for the strain rate tensor used in the SGS model are derived in terms
      of the nonequilibrium moments of the GLBE to include such forcing terms, which
      comprise a generalization of those presented in a recent work [Yu, Comput. Fluids
      35, 957 (2006)]. Variable resolutions are introduced into this extended GLBE
      framework through a conservative multiblock approach. The approach, whose
      optimized implementation is also discussed, is assessed for two canonical flow
      problems bounded by walls, viz., fully developed turbulent channel flow at a
      shear or friction Reynolds number (Re) of 183.6 based on the channel half-width
      and three-dimensional (3D) shear-driven flows in a cubical cavity at a Re of 12
      000 based on the side length of the cavity. Comparisons of detailed computed near
      wall turbulent flow structure, given in terms of various turbulence statistics,
      with available data, including those from direct numerical simulations (DNS) and
      experiments showed good agreement. The GLBE approach also exhibited markedly
      better stability characteristics and avoided spurious near-wall turbulent
      fluctuations on coarser grids when compared with the single-relaxation-time (SRT)
      based approach. Moreover, its implementation showed excellent parallel
      scalability on a large parallel cluster with over a thousand processors.

PMID- 19391871
TI  - Computation of turbulent flow and secondary motions in a square duct using a
      forced generalized lattice Boltzmann equation.
AB  - Turbulent flow in a straight square duct driven by a pressure gradient exhibits
      remarkable flow structures such as the presence of mean streamwise vorticity or
      secondary flows. These secondary circulations take the form of two counter
      rotating vortices near each corner of the duct. Even though their magnitudes are
      small compared with primary streamwise motions, they have a significant influence
      on flow and scalar transport and are challenging to accurately predict using
      computational approaches. In this paper, we employ a recently developed
      formulation of the generalized lattice Boltzmann equation (GLBE) with forcing
      term to perform large eddy simulation of fully developed turbulent flow in a
      square duct at a shear Reynolds number based on duct width equal to 300. Subgrid
      scale effects are represented by the Smagorinsky eddy viscosity model, which is
      modified by the van Driest damping function in the near-wall regions, in this
      GLBE approach, which is based on multiple relaxation times. It was found that the
      GLBE is able to correctly reproduce the existence of mean secondary motions and
      the computed detailed structure of first- and second-order statistics of main and
      secondary motions are in good agreement with prior direct numerical simulations
      based on the solution of the Navier-Stokes equations and experimental data.

PMID- 19391872
TI  - Spectral element method for band structures of two-dimensional anisotropic
      photonic crystals.
AB  - A spectral element method (SEM) is proposed for the accurate calculation of band
      structures of two-dimensional anisotropic photonic crystals. It uses Gauss
      Lobatto-Legendre polynomials as the basis functions in the finite-element
      framework with curvilinear quadrilateral elements. Coordination mapping is
      introduced to make the curved quadrilateral elements conformal with the problem
      geometry. Mixed order basis functions are used in the vector SEM for full vector
      calculation. The numerical convergence speed of the method is investigated with
      both square and triangular lattices, and with isotropic and in-plane anisotropic
      media. It is shown that this method has spectral accuracy, i.e., the numerical
      error decreases exponentially with the order of basis functions. With only four
      points per wavelength, the SEM can achieve a numerical error smaller than 0.1%.
      The full vector calculation method can suppress all spurious modes with nonzero
      eigenvalues, thus making it easy to filter out real modes. It is thus
      demonstrated that the SEM is an efficient alternative method for accurate
      determination of band structures of two-dimensional photonic crystals.

PMID- 19391873
TI  - Efficiency of rejection-free methods for dynamic Monte Carlo studies of off
      lattice interacting particles.
AB  - We calculate the efficiency of a rejection-free dynamic Monte Carlo method for d
      dimensional off-lattice homogeneous particles interacting through a repulsive
      power-law potential r(-p). Theoretically we find the algorithmic efficiency in
      the limit of low temperatures and/or high densities is asymptotically
      proportional to rho(p+2)/2T(-d/2) with the particle density rho and the
      temperature T. Dynamic Monte Carlo simulations are performed in one-, two-, and
      three-dimensional systems with different powers p, and the results agree with the
      theoretical predictions.

PMID- 19391874
TI  - Recursive algorithm for arrays of generalized Bessel functions: Numerical access
      to Dirac-Volkov solutions.
AB  - In the relativistic and the nonrelativistic theoretical treatment of moderate and
      high-power laser-matter interaction, the generalized Bessel function occurs
      naturally when a Schrodinger-Volkov and Dirac-Volkov solution is expanded into
      plane waves. For the evaluation of cross sections of quantum electrodynamic
      processes in a linearly polarized laser field, it is often necessary to evaluate
      large arrays of generalized Bessel functions, of arbitrary index but with fixed
      arguments. We show that the generalized Bessel function can be evaluated, in a
      numerically stable way, by utilizing a recurrence relation and a normalization
      condition only, without having to compute any initial value. We demonstrate the
      utility of the method by illustrating the quantum-classical correspondence of the
      Dirac-Volkov solutions via numerical calculations.

PMID- 19391875
TI  - Dynamical local field corrections on energy loss in plasmas of all degeneracies.
AB  - Random phase approximation (RPA) has become one of the most used methods to
      describe the energy loss of charged particles in plasmas. The RPA is usually
      valid for high-velocity projectiles and in the weak coupling limit of the
      electron gas. However, for partially coupled plasmas RPA is not sufficient and
      the electronic coupling must be taken into account. This coupling can be
      considered through local field corrections. In this work, we have constructed a
      dynamical local field correction (DLFC) function from Mermin dielectric function.
      This DLFC function has the advantage to describe plasmas at any degeneracy.
      Mermin DLFC function is compared with other DLFC functions from the literature in
      the energy loss calculation. We see important differences between them; they are
      significant at low velocities and very relevant around the maximum, almost 30%.

PMID- 19391876
TI  - Lattice Boltzmann model for thermal transpiration.
AB  - The conventional Navier-Stokes-Fourier equations with no-slip boundary conditions
      are unable to capture the phenomenon of gas thermal transpiration. While kinetic
      approaches such as the direct simulation Monte Carlo method and direct solution
      of the Boltzmann equation can predict thermal transpiration, these methods are
      often beyond the reach of current computer technology, especially for complex
      three-dimensional flows. We present a computationally efficient nonequilibrium
      thermal lattice Boltzmann model for simulating temperature-gradient-induced
      flows. The good agreement between our model and kinetic approaches demonstrates
      the capabilities of the proposed lattice Boltzmann method.

PMID- 19391877
TI  - Irreversibility and self-organization in hydrodynamic echo experiments.
AB  - We discuss the reversible-irreversible transition in low-Reynolds hydrodynamic
      systems driven by external cycling actuation. We introduce a set of models with
      no auto-organization, and show that a sharp crossover is obtained between a
      Lyapunov regime in which any noise source, such as thermal noise, is amplified
      exponentially, and a diffusive regime where this no longer holds. In the latter
      regime, groups of particles are seen to move cooperatively, yet no spatial
      organization occurs.

PMID- 19391878
TI  - Fluctuation ratios in the absence of microscopic time reversibility.
AB  - We study fluctuations in diffusion-limited reaction systems driven out of their
      stationary state. Using a numerically exact method, we investigate fluctuation
      ratios in various systems which differ by their level of violation of microscopic
      time reversibility. Studying a quantity that for an equilibrium system is related
      to the work done to the system, we observe that under certain conditions
      oscillations appear on top of an exponential behavior of transient fluctuation
      ratios. We argue that these oscillations encode properties of the probability
      currents in state space.

PMID- 19391879
TI  - Fluctuation properties of an effective nonlinear system subject to Poisson noise.
AB  - We study the work fluctuations of a particle, confined to a moving harmonic
      potential, under the influence of friction and external asymmetric Poissonian
      shot noise. This type of noise generalizes the usual Gaussian noise and induces
      an effective interaction between the noise and the potential, leading to an
      effectively nonlinear system with singular features. On the basis of an analytic
      solution we investigate the roles of time scales, symmetries, and singularities
      in the context of nonequilibrium fluctuations. Our results highlight the
      nonuniversality of the steady-state fluctuation theorem in stochastic systems.

PMID- 19391880
TI  - Resonant activation through effective temperature oscillation in a Josephson
      tunnel junction.
AB  - We experimentally investigated the thermal escape from a metastable state in a
      Josephson tunnel junction subjected to an oscillating effective temperature. A
      minimum of the average escape time is observed at certain oscillation frequency.
      Our results confirm that the resonant activation can be caused not only by the
      oscillating barrier but also by the oscillating temperature. The linear
      dependence of the minimum average escape time on the resonant frequency suggests
      that the correlation between the oscillation and the escape process leads to the
      resonant escape.

PMID- 19391881
TI  - Electrodynamic ratchet motor.
AB  - Brownian ratchets produce directed motion through rectification of thermal
      fluctuations and have been used for separation processes and colloidal transport.
      We propose a flashing ratchet motor that enables the transduction of electrical
      energy into rotary micromechanical work. This is achieved through torque
      generation provided by boundary shaping of equipotential surfaces. The present
      device contrasts to previous implementations that focus on translational motion.
      Stochastic simulations elucidate the performance characteristics of this device
      as a function of its geometry. Miniaturization to nanoscale dimensions yields
      rotational speeds in excess of 1 kHz, which is comparable to biomolecular motors
      of similar size.

PMID- 19391882
TI  - Macroscopic expression connecting the rate of energy dissipation with the
      violation of the fluctuation response relation.
AB  - A direct connection between the magnitude of the violation of the fluctuation
      response relation (FRR) and the rate of energy dissipation is presented in terms
      of field variables of nonequilibrium systems. Here, we consider the density field
      of a colloidal suspension either in a relaxation process or in a nonequilibrium
      steady state driven by an external field. Using a path-integral representation of
      the temporal evolution of the density field, we find an equality that relates the
      magnitude of the violation of the FRR for scalar and vector potentials of the
      velocity field to the rate of energy dissipation for the entire system. Our
      result demonstrates that the violation of the FRR for field variables captures
      the entropic component of the dissipated free energy.

PMID- 19391883
TI  - Geometrical frustration: a study of four-dimensional hard spheres.
AB  - The smallest maximum-kissing-number Voronoi polyhedron of three-dimensional (3D)
      Euclidean spheres is the icosahedron, and the tetrahedron is the smallest volume
      that can show up in Delaunay tessellation. No periodic lattice is consistent with
      either, and hence these dense packings are geometrically frustrated. Because
      icosahedra can be assembled from almost perfect tetrahedra, the terms
      "icosahedral" and "polytetrahedral" packing are often used interchangeably, which
      leaves the true origin of geometric frustration unclear. Here we report a
      computational study of freezing of 4D Euclidean hard spheres, where the densest
      Voronoi cluster is compatible with the symmetry of the densest crystal, while
      polytetrahedral order is not. We observe that, under otherwise comparable
      conditions, crystal nucleation in four dimensions is less facile than in three
      dimensions, which is consistent with earlier observations [M. Skoge, Phys. Rev. E
      74, 041127 (2006)]. We conclude that it is the geometrical frustration of
      polytetrahedral structures that inhibits crystallization.

PMID- 19391884
TI  - Relationship between structure, entropy, and mobility in network-forming ionic
      melts.
AB  - Diffusivity, ionic conductivity, and viscosity of network-forming ionic melts are
      examined using molecular dynamics simulations of BeF2 and SiO2 melts. These
      tetrahedral, network-forming ionic melts are shown to possess a conductivity
      anomaly, in addition to waterlike viscosity and diffusivity anomalies,
      corresponding to a striking breakdown of the Nernst-Einstein relation. The
      contrasting scaling behavior of the different mobility measures with different
      structural contributions to the excess entropy is demonstrated.

PMID- 19391885
TI  - Quantitative phase-field modeling of solidification at high Lewis number.
AB  - A phase-field model of nonisothermal solidification in dilute binary alloys is
      used to study the variation of growth velocity, dendrite tip radius, and radius
      selection parameter as a function of Lewis number at fixed undercooling. By the
      application of advanced numerical techniques, we have been able to extend the
      analysis to Lewis numbers of order 10 000, which are realistic for metals. A
      large variation in the radius selection parameter is found as the Lewis number is
      increased from 1 to 10 000.

PMID- 19391886
TI  - Electro-optic technique to study biaxiality of liquid crystals with positive
      dielectric anisotropy: the case of a bent-core material.
AB  - We propose that, for materials having positive dielectric anisotropy, the
      biaxiality can be clearly verified or excluded by measuring the transmitted light
      intensity as a function of electric field. If the material is biaxial and is
      observed in homeotropically aligned cells, the schlieren texture should not
      disappear (transmitted intensity is not zero) even at very high fields, since the
      field does not affect the distribution of the second director normal to the main
      director. On the other hand, if the material is uniaxial the transmitted
      intensity should decrease with increasing field and a perfect homeotropic texture
      can be achieved at high fields. We have studied a bent-core compound in which a
      uniaxial-biaxial nematic (N_{u}-N_{b}) transition has been reported. This
      material has a positive dielectric anisotropy at low frequencies, so we could
      apply the technique described above. Our studies indicate that the material is
      uniaxial in the entire nematic range.

PMID- 19391887
TI  - Optically induced orientational transitions in nematic liquid crystals with
      planar alignment.
AB  - A theoretical study of dynamical phenomena induced by linearly polarized light
      incident perpendicularly on a planar aligned nematic layer with the light
      intensity as the control parameter is reported. We find the threshold of the
      optically induced twist Freedericksz transition as a function of the problem
      parameters. The critical light intensity was found substantially lower than
      predicted earlier by Santamato [Phys. Rev. A 36, 2389 (1987)]. We have
      demonstrated by a rigorous stability analysis that the bifurcation is stationary
      only for a thickness of the nematic layer smaller than a certain critical value
      and becomes a Hopf bifurcation in the opposite case. Above the Hopf bifurcation
      an oscillatory state appears. It becomes unstable at a secondary threshold
      through a heteroclinic bifurcation, and the director settles to a new stationary
      distorted state.

PMID- 19391888
TI  - Critical Casimir effect in a polymer chain in supercritical solvents.
AB  - Density fluctuation effects on the conformation of a polymer chain in a
      supercritical solvent were investigated by performing a multiscale simulation
      based on the density-functional theory. We found (a) a universal swelling of the
      polymer chain near the critical point, irrespective of whether the polymer chain
      is solvophilic or solvophobic, and (b) a characteristic collapse of the polymer
      chain having a strong solvophilicity at a temperature slightly higher than the
      critical point, where the isothermal compressibility becomes less than the ideal
      one.

PMID- 19391889
TI  - Polymer desorption under pulling: a dichotomic phase transition.
AB  - The structural properties and phase behavior of a self-avoiding polymer chain on
      an adhesive substrate, subject to pulling at the chain end, are described by
      means of a grand canonical ensemble approach. We derive analytical expressions
      for the probability distributions of the basic structural units of an adsorbed
      polymer, such as loops, trains, and tails, in terms of the adhesive potential and
      applied pulling force f . In contrast to conventional, f=0 , polymer adsorption,
      the chain detachment transition under pulling turns out to be of first (rather
      than second) order, albeit it is dichotomic, i.e., no coexistence of different
      phase states exists. Also, the hitherto controversial value of the critical
      adsorption exponent varphi is found to depend essentially on the degree of
      interaction between different loops so that 0.34< or =varphi< or =0.59 . The
      theoretical predictions are verified by means of extensive Monte Carlo
      simulations.

PMID- 19391890
TI  - Quantized biopolymer translocation through nanopores: departure from simple
      scaling.
AB  - We discuss multiscale simulations of long biopolymer translocation through wide
      nanopores that can accommodate multiple polymer strands. The simulations provide
      clear evidence of folding quantization, namely the translocation proceeds through
      multifolded configurations characterized by a well-defined integer number of
      folds. As a consequence, the translocation time acquires a dependence on the
      average folding number, which results in a deviation from the single-exponent
      power law characterizing single-file translocation through narrow pores. The
      mechanism of folding quantization allows polymers above a threshold length
      (approximately 1000 persistence lengths for double-stranded DNA) to exhibit
      cooperative behavior, and as a result to translocate noticeably faster.

PMID- 19391891
TI  - Relationship between protein folding thermodynamics and the energy landscape.
AB  - The origin of protein folding thermodynamics is examined in terms of the energy
      landscape, employing an off-lattice protein model with scaled non-native
      attractions, which is continuously tunable between a Go-like model and a highly
      frustrated system. Extensive statistical temperature molecular dynamics
      simulations, combined with inherent structure analysis, reveal the intimate
      connection between the global geometric properties of the energy landscape and
      the statistical temperature. The basin depth of the energy landscape is shown to
      play a key role in the first-order-like characteristics of the statistical
      temperature, which are easily identified by the squared modulus of the potential
      energy gradient in the microcanonical ensemble.

PMID- 19391892
TI  - Probabilistic model of ligaments and tendons: quasistatic linear stretching.
AB  - Ligaments and tendons have a significant role in the musculoskeletal system and
      are frequently subjected to injury. This study presents a model of collagen
      fibers, based on the study of a statistical distribution of fibers when they are
      subjected to quasistatic linear stretching. With respect to other methodologies,
      this model is able to describe the behavior of the bundle using less ad hoc
      hypotheses and is able to describe all the quasistatic stretch-load responses of
      the bundle, including the yield and failure regions described in the literature.
      It has two other important results: the first is that it is able to correlate the
      mechanical behavior of the bundle with its internal structure, and it suggests a
      methodology to deduce the fibers population distribution directly from the
      tensile-test data. The second is that it can follow fibers' structure evolution
      during the stretching and it is possible to study the internal adaptation of
      fibers in physiological and pathological conditions.

PMID- 19391893
TI  - Diffusion in narrow domains and application to phototransduction.
AB  - The mean time for a Brownian particle to find a small target inside a narrow
      domain is a key parameter for many chemical reactions occurring in cellular
      microstructures. Although current estimations are given for a large class of
      domains, they cannot be used for narrow domains often encountered in cellular
      biology, such as the synaptic cleft, narrow compartments in the outer segment of
      vertebrate photoreceptors, or neuron-glia contact. We compute here the mean time
      for a Brownian particle to hit a small target placed on the surface of a narrow
      cylinder. We then use this result to estimate the rate constant of cyclic-GMP
      (cGMP) hydrolysis by the activated enzyme phosphodiesterase (PDE) in the narrow
      microdomains that build up the outer segment of a rod photoreceptor. By
      controlling the cGMP concentration, PDE activity is at the basis of the early
      photoresponse chemical reaction cascade. Our approach allows us to compute the
      cGMP rate constant as a function of biophysical parameters.

PMID- 19391894
TI  - Hydrophobicity at low temperatures and cold denaturation of a protein.
AB  - We elucidate the microscopic mechanism of the weakening of the hydrophobicity at
      low temperatures by investigating cold denaturation of a protein. We employ an
      elaborate statistical-mechanical theory combined with a realistic water model. At
      low temperatures, the ordered structure with enhanced hydrogen bonds of water
      molecules is formed near nonpolar groups, leading to entropic loss and energy
      gain which are both quite large. However, they are canceled out and make no
      contribution to the free-energy change. We argue that a different factor, which
      is responsible for the weakening of the hydrophobicity at low temperatures,
      induces cold denaturation.

PMID- 19391895
TI  - Line-defect patterns of unstable spiral waves in cardiac tissue.
AB  - Spiral wave propagation in period-2 excitable media is accompanied by line
      defects, the locus of points with period-1 oscillations. Here we investigate
      spiral line defects in cardiac tissue where period-2 behavior has a known
      arrhythmogenic role. We find that the number of line defects, which is
      constrained to be an odd integer, is 3 for a freely rotating spiral, with and
      without meander, but 1 for a spiral anchored around a fixed heterogeneity. We
      interpret this finding analytically using a simple theory where spiral wave
      unstable modes with different numbers of line defects correspond to quantized
      solutions of a Helmholtz equation. Furthermore, the slow inward rotation of
      spiral line defects is described in different regimes.

PMID- 19391896
TI  - Quantum fidelity and thermal phase transitions.
AB  - We study the quantum fidelity approach to characterize thermal phase transitions.
      Specifically, we focus on the mixed-state fidelity induced by a perturbation in
      temperature. We consider the behavior of fidelity in two types of second-order
      thermal phase transitions (based on the type of nonanaliticity of free energy),
      and we find that usual fidelity criteria for identifying critical points is more
      applicable to the case of lambda transitions (divergent second derivatives of
      free energy). Our study also reveals that for fixed perturbations, the
      sensitivity of fidelity at high temperatures (where thermal fluctuations wash out
      information about the transition) is reduced. From the connection to
      thermodynamical quantities we propose slight variations to the usual fidelity
      approach that allow us to overcome these limitations. In all cases we find that
      fidelity remains a good precriterion for testing thermal phase transitions, and
      we use it to analyze the nonzero temperature phase diagram of the Lipkin-Meshkov
      Glick model.

PMID- 19391897
TI  - From one solution of a 3-satisfiability formula to a solution cluster: frozen
      variables and entropy.
AB  - A solution to a 3-satisfiability (3-SAT) formula can be expanded into a cluster,
      all other solutions of which are reachable from this one through a sequence of
      single-spin flips. Some variables in the solution cluster are frozen to the same
      spin values by one of two different mechanisms: frozen-core formation and long
      range frustrations. While frozen cores are identified by a local whitening
      algorithm, long-range frustrations are very difficult to trace, and they make an
      entropic belief-propagation (BP) algorithm fail to converge. For the BP algorithm
      to reach a fixed point, the spin values of a tiny fraction of variables (chosen
      according to the whitening algorithm) are externally fixed during the iteration.
      From the calculated entropy values, we infer that, for a large random 3-SAT
      formula with constraint density close to the satisfiability threshold, the
      solutions obtained by the survey-propagation or WALKSAT algorithms belong neither
      to the most dominating clusters of the formula nor to the most abundant clusters.
      This work indicates that a single-solution cluster of a random 3-SAT formula may
      have further community structures.

PMID- 19391898
TI  - Phase transitions in diluted negative-weight percolation models.
AB  - We investigate the geometric properties of loops on two-dimensional lattice
      graphs, where edge weights are drawn from a distribution that allows for positive
      and negative weights. We are interested in the appearance of spanning loops of
      total negative weight. The resulting percolation problem is fundamentally
      different from conventional percolation, as we have seen in a previous study of
      this model for the undiluted case. Here, we investigate how the percolation
      transition is affected by additional dilution. We consider two types of dilution:
      either a certain fraction of edges exhibits zero weight, or a fraction of edges
      is even absent. We study these systems numerically using exact combinatorial
      optimization techniques based on suitable transformations of the graphs and
      applying matching algorithms. We perform a finite-size scaling analysis to obtain
      the phase diagram and determine the critical properties of the phase boundary. We
      find that the first type of dilution does not change the universality class
      compared to the undiluted case whereas the second type of dilution leads to a
      change in the universality class.

PMID- 19391899
TI  - Linear stochastic system with delay: energy balance and entropy production.
AB  - We study the energy balance in a linear stochastic dynamics with delay under the
      impact of an external periodic force. The linearity of the model, in combination
      with a response function method, enables us to perform detailed analytic
      calculations of each term in the energy balance equation. From this, we discuss
      thermodynamics and entropy production rate sigma . With use of the delay time tau
      and strength of the external force A0 , sigma is simply expressed as
      sigma=sigma_{D,1}(tau)+A_{0};{2}eta(tau) , with both sigma_{D,1}(tau) and
      eta(tau) positive definite. We thus conclude that even when there is no external
      force (A_{0}=0) , the entropy production rate sigma=sigma_{D,1}(tau) is positive,
      meaning that the delay force produces work, which is dissipated into a reservoir.
      Numerical experiments are performed to confirm theoretical results.

PMID- 19391900
TI  - Generalizing Landauer's principle.
AB  - In a recent paper [Stud. Hist. Philos. Mod. Phys. 36, 355 (2005)] it is argued
      that to properly understand the thermodynamics of Landauer's principle it is
      necessary to extend the concept of logical operations to include indeterministic
      operations. Here we examine the thermodynamics of such operations in more detail,
      extending the work of Landauer to include indeterministic operations and to
      include logical states with variable entropies, temperatures, and mean energies.
      We derive the most general statement of Landauer's principle and prove its
      universality, extending considerably the validity of previous proofs. This
      confirms conjectures made that all logical operations may, in principle, be
      performed in a thermodynamically reversible fashion, although logically
      irreversible operations would require special, practically rather difficult,
      conditions to do so. We demonstrate a physical process that can perform any
      computation without work requirements or heat exchange with the environment. Many
      widespread statements of Landauer's principle are shown to be special cases of
      our generalized principle.

PMID- 19391901
TI  - Response theory and reduced equations of motion.
AB  - Nonlinear response theory for a relaxation experiment is used to derive classical
      and quantum-mechanical equations of motion for reduced distribution functions or
      density matrices, respectively. The classical equations are linear, but the
      quantum ones are not. The results are analyzed in the weak-coupling and
      separation-of-time-scales limits.

PMID- 19391902
TI  - Disordered driven lattice gases with boundary reservoirs and Langmuir kinetics.
AB  - The asymmetric simple exclusion process with additional Langmuir kinetics, i.e.,
      attachment and detachment in the bulk, is a paradigmatic model for intracellular
      transport. Here we study this model in the presence of randomly distributed
      inhomogeneities ("defects"). Using Monte Carlo simulations, we find a multitude
      of coexisting high- and low-density domains. The results are generic for one
      dimensional driven diffusive systems with short-range interactions and can be
      understood in terms of a local extremal principle for the current profile. This
      principle is used to determine current profiles and phase diagrams as well as
      statistical properties of ensembles of defect samples.

PMID- 19391903
TI  - Density matrix for the kink ground state of the ferromagnetic XXZ chain.
AB  - The exact expression for the density matrix of the kink ground state of the
      ferromagnetic XXZ chain is obtained. Utilizing this, we exactly calculate various
      correlation functions such as the longitudinal and transverse spin-spin
      correlation functions, and the ferromagnetic and antiferromagnetic string
      formation probabilities. The asymptotic behaviors of these correlation functions
      are also analyzed. As a consequence, we find that the spin-spin correlation
      functions decay exponentially for large distances, while the string formation
      probabilities exhibit Gaussian decay for large strings. We also evaluate the
      entanglement entropy, which shows interesting behaviors due to the lack of the
      translational invariance of the state.

PMID- 19391904
TI  - Field theory of bicritical and tetracritical points. III. Relaxational dynamics
      including conservation of magnetization (model C).
AB  - We calculate the relaxational dynamical critical behavior of systems of O(n_{
      parallel}) plus sign in circleO(n_{ perpendicular}) symmetry including
      conservation of magnetization by renormalization group theory within the minimal
      subtraction scheme in two-loop order. Within the stability region of the
      Heisenberg fixed point and the biconical fixed point, strong dynamical scaling
      holds, with the asymptotic dynamical critical exponent z=2varphinu-1 , where
      varphi is the crossover exponent and nu the exponent of the correlation length.
      The critical dynamics at n_{ parallel}=1 and n_{ perpendicular}=2 is governed by
      a small dynamical transient exponent leading to nonuniversal nonasymptotic
      dynamical behavior. This may be seen, e.g., in the temperature dependence of the
      magnetic transport coefficients.

PMID- 19391905
TI  - Different thresholds of bond percolation in scale-free networks with identical
      degree sequence.
AB  - Generally, the threshold of percolation in complex networks depends on the
      underlying structural characterization. However, what topological property plays
      a predominant role is still unknown, despite the speculation of some authors that
      degree distribution is a key ingredient. The purpose of this paper is to show
      that power-law degree distribution itself is not sufficient to characterize the
      threshold of bond percolation in scale-free networks. To achieve this goal, we
      first propose a family of scale-free networks with the same degree sequence and
      obtain by analytical or numerical means several topological features of the
      networks. Then, by making use of the renormalization-group technique we determine
      the threshold of bond percolation in our networks. We find an existence of
      nonzero thresholds and demonstrate that these thresholds can be quite different,
      which implies that power-law degree distribution does not suffice to characterize
      the percolation threshold in scale-free networks.

PMID- 19391906
TI  - Continuum diffusion on networks: trees with hyperbranched trunks and fractal
      branches.
AB  - The probability that a random walker returns to its origin for large times scales
      as t;{-d[over ]2} , where d[over ] is the spectral dimension. We calculate d[over
      ] for a class of tree structures using a renormalization technique on an infinite
      continued fraction. We consider a wide range of homogeneous networks based on
      replacing the branches of a self-similar tree with arbitrary fractals and
      composite fractals. We also consider a new class of inhomogeneous hyperbranched
      trees.

PMID- 19391907
TI  - Persistence in advection of a passive scalar.
AB  - We consider the persistence phenomenon in advected passive scalar equation in one
      dimension. The velocity field is random with the v(k,omega)v(-k,-omega)
      approximately mid R:kmid R:;{-(2+alpha)} . In the presence of the nonlinearity
      the complete Green's function becomes G;{-1}=-iomega+Dk2+Sigma . We determine
      Sigma self-consistently from the correlation function which gives Sigma
      approximately k;{beta} , with beta=(1-alpha)2 . The effect of the nonlinear term
      in the equation in the O(;{2}) is to replace the diffusion term due to molecular
      viscosity by an effective term of the form Sigma_{0}k;{beta} . The stationary
      correlator for this system is [sech(T2)];{1beta} . Using the self-consistent
      theory we have determined the relation between beta and alpha . Finally, the
      independent interval approximation (IIA) method is used to determine the
      persistent exponent.

PMID- 19391908
TI  - Quantized heat transport in small systems: a phenomenological approach.
AB  - Recent progress in nanoscale materials science has pushed the basic research on
      physical effects while going to such length scales. Particularly, the study of
      size effects on heat conductivity has attracted much theoretical and experimental
      interest. In this work we explore the possibilities to study such kinds of
      phenomena through the quantization of the dynamic equations of a class of
      nonlinear heat transport macroscopic models. We develop a quantization procedure
      to search the energy level structure of one-dimensional nanosystems. The
      procedure may have applications in other fields of the physics of mesoscopic
      systems.

PMID- 19391909
TI  - Ratchet effect of a dimer with broken friction symmetry in a symmetric potential.
AB  - The one-dimensional overdamped Brownian motion of a dimer consisting of two
      harmonically interacting components is considered. Both components are coupled to
      the same heat bath and feel the same spatially periodic symmetric potential,
      whose amplitude is modulated periodically in time. The friction coefficients may
      differ between dimer components, thus breaking the dynamical symmetry of the
      system. In the absence of any external bias, a ratchet effect (directed
      transport) arises generically. Two accurate approximations for the dimer's
      velocity and diffusion coefficient are obtained for weak and strong couplings.
      The velocity of the system can be maximized for each direction by adding an
      optimal amount of noise and by tuning the driving frequency to an optimal value.
      Furthermore, there exist two optimal coupling strengths at which the velocity is
      the largest.

PMID- 19391910
TI  - Analytical investigation of the open boundary conditions in the Nagel
      Schreckenberg model.
AB  - We theoretically investigate the mechanism of the open boundary conditions in the
      deterministic Nagel-Schreckenberg model, which was studied mainly by numerical
      simulations before. Our studies concentrate on the open boundaries and have found
      an effective approach for deducing the analytical expression of inflow. We also
      raise a removal rule which is analyzable. These findings provide a theoretical
      explanation of the behaviors of the open boundaries and allow the exact
      prediction of the traffic state by using the injection rate and the removal rate.

PMID- 19391911
TI  - Modeling long-range memory with stationary Markovian processes.
AB  - In this paper we give explicit examples of long-range correlated stationary
      Markovian processes y(t) where the stationary probability density function (pdf)
      shows tails which are Gaussian or exponential. These processes are obtained by
      simply performing appropriate coordinate transformations of a specific power-law
      correlated additive process x(t) , already known in the literature, whose pdf
      shows power-law tails. We give analytical and numerical evidences that although
      the new processes are Markovian and have Gaussian or exponential tails, their
      autocorrelation function shows a power-law decay with logarithmic corrections.
      For a generic continuous and monotonously increasing coordinate transformation,
      we also analytically investigate what is the relationship between the asymptotic
      decay of the autocorrelation function and the tails of the stationary pdf.
      Extreme events seem to be associated to long-range correlated processes with
      power-law decaying autocorrelation function. However, the occurrence of extreme
      events is not necessary in order to have more general long-range correlated
      processes in which the autocorrelation shows a slow decay characterized by a
      power-law times a correction function such as the logarithm. Our results help in
      clarifying that even in the context of stationary Markovian processes long-range
      dependencies are not necessarily associated to the occurrence of extreme events.
      Moreover, our results can be relevant in the modeling of complex systems with
      long memory. In fact, we provide simple stationary processes associated to
      Langevin equations with white noise thus confirming that long-memory effects can
      be modeled in the context of continuous time stationary Markovian processes.

PMID- 19391912
TI  - Deformations of the Tracy-Widom distribution.
AB  - In random matrix theory, the Tracy-Widom (TW) distribution describes the behavior
      of the largest eigenvalue. We consider here two models in which TW undergoes
      transformations. In the first one disorder is introduced in the Gaussian
      ensembles by superimposing an external source of randomness. A competition
      between TW and a normal (Gaussian) distribution results, depending on the
      spreading of the disorder. The second model consists of removing at random a
      fraction of (correlated) eigenvalues of a random matrix. The usual formalism of
      Fredholm determinants extends naturally. A continuous transition from TW to the
      Weilbull distribution, characteristic of extreme values of an uncorrelated
      sequence, is obtained.

PMID- 19391913
TI  - Optimal potentials for temperature ratchets.
AB  - In a spatially periodic temperature profile, directed transport of an overdamped
      Brownian particle can be induced along a periodic potential. With a load force
      applied to the particle, this setup can perform as a heat engine. For a given
      load, the optimal potential maximizes the current and thus the power output of
      the heat engine. We calculate the optimal potential for different temperature
      profiles and show that in the limit of a periodic piecewise constant temperature
      profile alternating between two temperatures, the optimal potential leads to a
      divergent current. This divergence, being an effect of both the overdamped limit
      and the infinite temperature gradient at the interface, would be cut off in any
      real experiment.

PMID- 19391914
TI  - Statistical theory of critical phenomena in fluids.
AB  - We show that there are two classes of the closure equations for the Ornstein
      Zernike equation: The analytical equations for the bridge functional B=B;{(an)}
      like hypernetted-chain approximation, Percus-Yevick approximation, etc., and
      nonanalytic equation B=B;{(nan)} , where B;{(nan)}=B;{(rg)}+B;{(cr)} and B;{(rg)}
      is the regular (analytical) component of the bridge functional, and B;{(cr)} is
      the critical (nonanalytical) component of B;{(nan)} . The closure equation
      B;{(an)} defines coordinates of the critical point and other individual features
      of critical phenomena, and B;{(nan)} defines all the known relations between
      critical exponents. It is shown, that the necessary condition for existence of
      the nonanalytic solution of the OZ equation is the equality 5-eta=delta(1+eta) ,
      where eta,delta are the critical exponents, values of which can change in a
      narrow interval. We also show that the transition from the analytical solution to
      the nonanalytic one is accompanied by a break of the pressure derivative. The
      boundaries between the areas, where each of these solutions exists, are indicated
      on the phase diagram.

PMID- 19391915
TI  - Truncation effects in superdiffusive front propagation with Levy flights.
AB  - A numerical and analytical study of the role of exponentially truncated Levy
      flights in the superdiffusive propagation of fronts in reaction-diffusion systems
      is presented. The study is based on a variation of the Fisher-Kolmogorov equation
      where the diffusion operator is replaced by a lambda -truncated fractional
      derivative of order alpha , where 1lambda is the characteristic truncation length
      scale. For lambda=0 there is no truncation, and fronts exhibit exponential
      acceleration and algebraically decaying tails. It is shown that for lambda not
      equal0 this phenomenology prevails in the intermediate asymptotic regime
      (chit);{1alpha}x1lambda where chi is the diffusion constant. Outside the
      intermediate asymptotic regime, i.e., for x>1lambda , the tail of the front
      exhibits the tempered decay varphi approximately e;{-lambdax}x;{(1+alpha)} , the
      acceleration is transient, and the front velocity v_{L} approaches the terminal
      speed v_{*}=(gamma-lambda;{alpha}chi)lambda as t-->infinity , where it is assumed
      that gamma>lambda;{alpha}chi with gamma denoting the growth rate of the reaction
      kinetics. However, the convergence of this process is algebraic, v_{L}
      approximately v_{*}-alpha(lambdat) , which is very slow compared to the
      exponential convergence observed in the diffusive (Gaussian) case. An
      overtruncated regime in which the characteristic truncation length scale is
      shorter than the length scale of the decay of the initial condition, 1nu , is
      also identified. In this extreme regime, fronts exhibit exponential tails, varphi
      approximately e;{-nux} , and move at the constant velocity v=(gamma
      lambda;{alpha}chi)nu .

PMID- 19391916
TI  - Direct evidence for conformal invariance of avalanche frontiers in sandpile
      models.
AB  - Appreciation of stochastic Loewner evolution (SLE_{kappa}) , as a powerful tool
      to check for conformal invariant properties of geometrical features of critical
      systems has been rising. In this paper we use this method to check conformal
      invariance in sandpile models. Avalanche frontiers in Abelian sandpile model are
      numerically shown to be conformally invariant and can be described by SLE with
      diffusivity kappa=2 . This value is the same as value obtained for loop-erased
      random walks. The fractal dimension and Schramm's formula for left passage
      probability also suggest the same result. We also check the same properties for
      Zhang's sandpile model.

PMID- 19391917
TI  - Ultrametricity property of energy landscapes of multidisperse packing problems.
AB  - We consider the problem of finding the densest closed packing of hard disks with
      proposed different radii in a circular environment, such that the radius of the
      circumcircle is minimal. The subspace of the quasioptimum configurations of this
      problem exhibits the property of ultrametricity.

PMID- 19391918
TI  - Dense sphere packings from optimized correlation functions.
AB  - Elementary smooth functions (beyond contact) are employed to construct pair
      correlation functions that mimic jammed disordered sphere packings. Using the
      g_{2} -invariant optimization method of Torquato and Stillinger [J. Phys. Chem. B
      106, 8354 (2002)], parameters in these functions are optimized under necessary
      realizability conditions to maximize the packing fraction varphi and average
      number of contacts per sphere Z . A pair correlation function that incorporates
      the salient features of a disordered packing and that is smooth beyond contact is
      shown to permit a varphi of 0.6850: this value represents a 45% reduction in the
      difference between the maximum for congruent hard spheres in three dimensions,
      pi/sqrt[18] approximately 0.7405 and 0.64, the approximate fraction associated
      with maximally random jammed packings in three dimensions. We show that,
      surprisingly, the continued addition of elementary functions consisting of smooth
      sinusoids decaying as r;{-4} permits packing fractions approaching pi/sqrt[18] .
      A translational order metric is used to discriminate between degrees of order in
      the packings presented. We find that to achieve higher packing fractions, the
      degree of order must increase, which is consistent with the results of a previous
      study [Torquato, Phys. Rev. Lett. 84, 2064 (2000)].

PMID- 19391919
TI  - Statistical thermodynamics of a two-dimensional relativistic gas.
AB  - In this paper we study a fully relativistic model of a two-dimensional hard-disk
      gas. This model avoids the general problems associated with relativistic particle
      collisions and is therefore an ideal system to study relativistic effects in
      statistical thermodynamics. We study this model using molecular-dynamics
      simulation, concentrating on the velocity distribution functions. We obtain
      results for x and y components of velocity in the rest frame (Gamma) as well as
      the moving frame (Gamma;{'}) . Our results confirm that Juttner distribution is
      the correct generalization of Maxwell-Boltzmann distribution. We obtain the same
      "temperature" parameter beta for both frames consistent with a recent study of a
      limited one-dimensional model. We also address the controversial topic of
      temperature transformation. We show that while local thermal equilibrium holds in
      the moving frame, relying on statistical methods such as distribution functions
      or equipartition theorem are ultimately inconclusive in deciding on a correct
      temperature transformation law (if any).

PMID- 19391920
TI  - Self-tuning phase separation in a model with competing interactions inspired by
      biological cell polarization.
AB  - We present a theoretical study of a system with competing short-range
      ferromagnetic attraction and a long-range antiferromagnetic repulsion, in the
      presence of a uniform external magnetic field. The interplay between these
      interactions, at sufficiently low temperature, leads to the self-tuning of the
      magnetization to a value which triggers phase coexistence, even in the presence
      of the external field. The investigation of this phenomenon is performed using a
      Ginzburg-Landau functional in the limit of an infinite number of order parameter
      components (large N model). The scalar version of the model is expected to
      describe the phase separation taking place on a cell surface when this is
      immersed in a uniform concentration of chemical stimulant. A phase diagram is
      obtained as a function of the external field and the intensity of the long-range
      repulsion. The time evolution of the order parameter and of the structure factor
      in a relaxation process is studied in different regions of the phase diagram.

PMID- 19391921
TI  - Statistical physics of power fluctuations in mode-locked lasers.
AB  - We present an analysis of the power fluctuations in the statistical steady state
      of a passively mode-locked laser. We use statistical light-mode theory to map
      this problem to that of fluctuations in a reference equilibrium statistical
      physics problem and, in this way, study the fluctuations nonperturbatively. The
      power fluctuations, being noncritical, are Gaussian and proportional in amplitude
      to the inverse square root of the number of degrees of freedom. We calculate
      explicit analytic expressions for the covariance matrix of the overall pulse and
      cw power variables, providing complete information on the single-time power
      distribution in the laser, and derive a set of fluctuation-dissipation relations
      between them and the susceptibilities of the steady-state quantities.

PMID- 19391922
TI  - Deviation from Archie's law in partially saturated porous media: Wetting film
      versus disconnectedness of the conducting phase.
AB  - We experimentally study the electrical transport in partially water-saturated
      pore network. The porous medium under investigation is a Fontainebleau sandstone,
      characterized by x-ray tomography. We show the existence of two electrical
      conductivity regimes. At high water saturation, the electric resistivity follows
      a well-known Archie law. Below a water saturation S_{w} approximately 0.2 , a
      strong negative deviation from this Archie law is observed. We attribute this
      transition to the existence of "a thick liquid film," assuring the ionic
      conduction in the low saturation regime. A numerical simulation is proposed to
      confirm this scenario. Two possible protocols are used to distribute the brine
      phase in the pore network of a three-dimensional microtomography image. The first
      one is based on a minimization of the interfacial energy. The second takes into
      account a quasistatic capillary displacement. The classical random-walk algorithm
      is used to compute the electric conductivity at various water saturations.
      Without the "thick film," both of the two fluid-placing protocols show a
      disconnectedness transition of the brine phase when S_{w}<0.2 . Adding this
      "film" to solid surface, the electrical continuity is maintained. The bending
      down trend is correctly reproduced, showing that in this range, the electric
      response cannot be described by a power law as usual.

PMID- 19391923
TI  - Equilibrium states of a test particle coupled to finite-size heat baths.
AB  - We report on numerical simulations of the dynamics of a test particle coupled to
      competing Boltzmann heat baths of finite size. After discussing some features of
      the single bath case, we show that the presence of two heat baths further
      constrains the conditions necessary for the test particle to thermalize with the
      heat baths. We find that thermalization is a spectral property in which the
      oscillators of the bath with frequencies in the range of the test particle
      characteristic frequency determine its degree of thermalization. We also find an
      unexpected frequency shift of the test particle response with respect to the
      spectra of the two heat baths. Finally, we discuss implications of our results
      for the study of high-frequency nanomechanical resonators through cold damping
      cooling techniques and for engineering reservoirs capable of mitigating the back
      action on a mechanical system.

PMID- 19391924
TI  - Log-amplitude statistics of intermittent and non-Gaussian time series.
AB  - In studies of hydrodynamic turbulence and nonequilibrium systems, it has been
      demonstrated that the observed non-Gaussian probability density functions are
      often described effectively by a superposition of Gaussian distributions with
      fluctuating variances. Based on this framework, we propose a general method to
      characterize intermittent and non-Gaussian time series. In our approach, an
      observed time series is assumed to be described by the multiplication of Gaussian
      and amplitude random variables, where the amplitude variable describes the
      variance fluctuation. It is shown analytically that statistical properties of the
      log-amplitude fluctuations can be estimated using the logarithmic-absolute
      moments of the observed time series. This method is applicable to a wide variety
      of symmetric unimodal distributions with heavy tails in order to quantify the
      deviation from a Gaussian distribution. By analyzing random cascade-type
      processes and superstatistical non-Gaussian models with power-law tails, we
      demonstrate that our method can provide detailed characterization in a wide range
      of non-Gaussian fluctuations.

PMID- 19391925
TI  - Transition to irreversibility in sheared suspensions: an analysis based on a
      mesoscopic entropy production.
AB  - We study the shear-induced diffusion effect and the transition to irreversibility
      in suspensions under oscillatory shear flow by performing an analysis of the
      entropy production associated with the motion of the particles. We show that the
      Onsager coupling between different contributions to the entropy production is
      responsible for the scaling of the mean square displacement on particle diameter
      and applied strain. We also show that the shear-induced effective diffusion
      coefficient depends on the volume fraction, and use lattice-Boltzmann simulations
      to characterize the effect through the power spectrum of particle positions for
      different Reynolds numbers and volume fractions. Our study gives a thermodynamic
      explanation of the transition to irreversibility through a pertinent analysis of
      the second law of thermodynamics.

PMID- 19391926
TI  - Molecular dynamics simulation of collision operator eigenvalues.
AB  - We simulate numerically the time evolution of 1000 interacting hard spheres in a
      finite box with periodic boundary conditions, and repeat the simulations many
      times for a selected random distribution of initial conditions. We use the
      resulting data to compute, directly, the smallest nonzero eigenvalue of the
      collision operator for this gas. We also give exact expressions for the transport
      coefficients and compare them to approximate expressions commonly seen in the
      literature.

PMID- 19391927
TI  - Anomalous structure and dynamics of the Gaussian-core fluid.
AB  - It is known that there are thermodynamic states for which the Gaussian-core fluid
      displays anomalous properties such as expansion upon isobaric cooling (density
      anomaly) and increased single-particle mobility upon isothermal compression (self
      diffusivity anomaly). Here, we investigate how temperature and density affect its
      short-range translational structural order, as characterized by the two-body
      excess entropy. We find that there is a wide range of conditions for which the
      short-range translational order of the Gaussian-core fluid decreases upon
      isothermal compression (structural order anomaly). As we show, the origin of the
      structural anomaly is qualitatively similar to that of other anomalous fluids
      (e.g., water or colloids with short-range attractions) and is connected to how
      compression affects static correlations at different length scales.
      Interestingly, we find that the self-diffusivity of the Gaussian-core fluid obeys
      a scaling relationship with the two-body excess entropy that is very similar to
      the one observed for a variety of simple liquids. One consequence of this
      relationship is that the state points for which structural, self-diffusivity, and
      density anomalies of the Gaussian-core fluid occur appear as cascading regions on
      the temperature-density plane; a phenomenon observed earlier for models of
      waterlike fluids. There are, however, key differences between the anomalies of
      Gaussian-core and waterlike fluids, and we discuss how those can be qualitatively
      understood by considering the respective interparticle potentials of these
      models. Finally, we note that the self-diffusivity of the Gaussian-core fluid
      obeys different scaling laws depending on whether the two-body or total excess
      entropy is considered. This finding, which deserves more comprehensive future
      study, appears to underscore the significance of higher-body correlations for the
      behavior of fluids with bounded interactions.

PMID- 19391928
TI  - Soret effect in molecular mixtures.
AB  - A theoretical approach to the description of the Soret effect in binary nonpolar
      liquids is proposed. The temperature gradient of the partial pressure is
      determined as the driving force of thermal diffusion. The hard-sphere fluid is
      chosen as a reference system and an explicit relation for the Soret coefficient
      is found. Two additive contributions owing to steric repulsions and attractive
      interactions form the so-called chemical contribution to S_{T} [C. Debuschewitz
      and W. Kohler, Phys. Rev. Lett. 87, 055901 (2001)]. The parameters of
      interparticle interactions are defined with the help of the solvation theory. In
      particular, the van der Waals constant of cross interactions is expressed via the
      excess volume of mixture. The proposed theory is applied to the benzene
      cyclohexane system. A reasonable agreement of theoretical and experimental
      results is revealed for the Soret coefficient and its temperature dependence.

PMID- 19391929
TI  - Driven inelastic-particle systems with drag.
AB  - We study steady states of the motion of a large number of particles in a closed
      box that are excited by a vibrating boundary and experience a linear drag force
      from the interstitial fluid. The dissipation in such systems arises from two main
      sources: Inelasticity in particle collisions and the effects of interstitial
      fluid on the particles. In many applications, order of magnitude estimates
      suggest that the dissipation due to interstitial fluid effects may greatly exceed
      that due to inelasticity and one is naturally led to neglect inelastic effects.
      In this study, we show that, if one adopts a linear drag force and inelastic
      effects are neglected, a steady state only exists when the vibration speed of the
      boundary is below a critical value. For vibration speeds above this critical
      value, no steady state exists since the kinetic energy of the particles grows
      without bound. We show that, for vibration speeds above the critical value,
      inelastic effects must be included to obtain a steady state even if order of
      magnitude estimates suggest they are negligible. Numerical simulations confirm
      these theoretical predictions. We also show that inclusion of apparently small
      nonlinear drag terms can also play a similar role in preventing the kinetic
      energy of the particles growing without bound.

PMID- 19391930
TI  - Flow-rate fluctuations in the outpouring of grains from a two-dimensional silo.
AB  - We present experimental results obtained with a two-dimensional silo discharging
      under gravity through an orifice at the flat bottom. High-speed measurements
      provide enough time resolution to detect every single bead that goes out and this
      allows the measurement of the flow rate in short-time windows. Two different
      regimes are clearly distinguished: one for large orifices, which can be described
      by Gaussian fluctuations, and another for small orifices, in which extreme events
      appear. The frontier between those two regimes coincides with the outlet size
      below which jamming events are frequent. Moreover, it is shown that the power
      spectrum of the flow-rate oscillations is not dominated by any particular
      frequency.

PMID- 19391931
TI  - Formation of aeolian ripples and sand sorting.
AB  - We present a continuous model capable of demonstrating some salient features of
      aeolian sand ripples: the realistic asymmetric ripple shape, coarsening of the
      ripple field at the nonlinear stage of ripple growth, saturation of ripple growth
      for homogeneous sand, typical size segregation of sand, and formation of armoring
      layers of coarse particles on ripple crests and windward slopes if the sand is
      inhomogeneous.

PMID- 19391932
TI  - Effective boundary conditions for dense granular flows.
AB  - We derive an effective boundary condition for dense granular flow taking into
      account the effect of the heterogeneity of the force network on sliding friction
      dynamics. This yields an intermediate boundary condition which lies in the limit
      between no slip and Coulomb friction; two simple functions relating wall stress,
      velocity, and velocity variance are found from numerical simulations. Moreover,
      we show that this effective boundary condition corresponds to Navier slip
      condition when the model of G. D. R. Midi [Eur. Phys. J. E 14, 341 (2004)] is
      assumed to be valid, and that the slip length depends on the length scale that
      characterizes the system, viz. the particle diameter.

PMID- 19391933
TI  - Vibrated granular gas confined by a piston.
AB  - The steady state of a vibrated granular gas confined by a movable piston on top
      is discussed. Particular attention is given to the hydrodynamic boundary
      conditions to be used when solving the inelastic Navier-Stokes equations. The
      relevance of an exact general condition relating the grain fluxes approaching and
      moving away from each of the walls is emphasized. It is shown how it can be used
      to get a consistent hydrodynamic description of the boundaries. The obtained
      expressions for the fields do not contain any undetermined parameter. Comparison
      of the theoretical predictions with molecular-dynamics simulation results is
      carried out, and a good agreement is observed for low density and not too large
      inelasticity. A practical way of introducing small finite density corrections to
      the dilute limit theory is proposed to improve the accuracy of the theory.

PMID- 19391934
TI  - Magnetofluidization of fine magnetite powder.
AB  - The behavior of a fluidized bed of fine magnetite particles as affected by a
      cross-flow magnetic field is investigated. A distinct feature of this naturally
      cohesive powder, as compared to noncohesive magnetic grains usually employed in
      magnetofluidized beds, is that the fluidized bed displays a range of stable
      fluidization even in the absence of an external magnetic field. Upon application
      of the magnetic field, the interval of stable fluidization is extended to higher
      gas velocities and bed expansion is enhanced. We have measured the tensile
      strength as affected by application of the external magnetic field according to
      two different operation modes. In the H off-on operation mode, the bed is driven
      to bubbling in the absence of external magnetic field. Once the gas velocity is
      decreased below the bubbling onset and the bed has returned to stable
      fluidization due to natural cohesive forces, the field is applied. In the H on-on
      mode, the field is maintained during the whole process of bubbling and return to
      stable fluidization. It is found that the tensile strength of the naturally
      stabilized bed is not essentially changed by application of the field ( H off-on)
      since the magnetic field cannot alter the bed structure once the particles are
      jammed in the stable fluidization state. Magnetic forces within the bulk of the
      jammed bed are partially canceled as a result of the anisotropic nature of the
      dipole-dipole interaction between the particles, which gives rise to just a small
      increment of the tensile strength. On the other hand, when the field is held on
      during bubbling and transition to stable fluidization ( H on-on mode), the
      tensile strength is appreciably increased. This suggests the formation of
      particle chains when the particles are not constrained due to the dipole-dipole
      attractive interaction which affects the mechanical strength of the stably
      fluidized bed. Experimental data are analyzed in the light of theoretical models
      on magnetic surface stresses.

PMID- 19391935
TI  - Axial and radial segregation of granular mixtures in a rotating spherical
      container.
AB  - We report the formation of axial segregation patterns of bidisperse granular
      mixtures of glass beads in a spherical container which is rotated about a central
      axis. When the rotation axis is horizontal, three distinct segregation bands are
      formed for a broad range of geometrical and dynamical parameters. We find two
      distinct regimes: at low fill levels the small size beads of the mixture are
      collected at the poles and the large size beads in a central band. At high fill
      levels the pole regions are occupied by large beads, while the small beads form
      the central band. The critical fill level for this structural transition
      decreases with increasing container size. For a container with 37 mm inner
      diameter, containing a mixture of 0.5 and 1.5 mm beads, the transition occurs
      between 40% and 50% fill level. When the rotation axis is tilted, the band
      positions are shifted and two-band structures are formed with the smaller
      particles at the lower pole. In our experiments the granulate is submersed in
      water; this allows NMR imaging of the complete three-dimensional band structures.
      We compare the observed segregation structures to those in cylindrical mixers and
      propose a model for the qualitative explanation of the pattern formation process.

PMID- 19391936
TI  - Role of interparticle friction and particle-scale elasticity in the shear
      strength mechanism of three-dimensional granular media.
AB  - The interlink between particle-scale properties and macroscopic behavior of three
      dimensional granular media subjected to mechanical loading is studied intensively
      by scientists and engineers, but not yet well understood. Here we study the role
      of key particle-scale properties, such as interparticle friction and particle
      elastic modulus, in the functioning of dual contact force networks, viz., strong
      and weak contacts, in mobilizing shear strength in dense granular media subjected
      to quasistatic shearing. The study is based on three-dimensional discrete element
      method in which particle-scale constitutive relations are based on well
      established nonlinear theories of contact mechanics. The underlying distinctive
      contributions of these force networks to the macroscopic stress tensor of sheared
      granular media are examined here in detail to find out how particle-scale
      friction and particle-scale elasticity (or particle-scale stiffness) affect the
      mechanism of mobilization of macroscopic shear strength and other related
      properties. We reveal that interparticle friction mobilizes shear strength
      through bimodal contribution, i.e., through both major and minor principal
      stresses. However, against expectation, the contribution of particle-scale
      elasticity is mostly unimodal, i.e., through the minor principal stress
      component, but hardly by the major principal stress. The packing fraction and the
      geometric stability of the assemblies (expressed by the mechanical coordination
      number) increase for decrease in interparticle friction and elasticity of
      particles. Although peak shear strength increases with interparticle friction,
      the deviator strain level at which granular systems attain peak shear strength is
      mostly independent of interparticle friction. Granular assemblies attain peak
      shear strength (and maximum fabric anisotropy of strong contacts) when a critical
      value of the mechanical coordination number is attained. Irrespective of the
      interparticle friction and elasticity of the particles, the packing fraction and
      volumetric strain are constant during steady state. Volumetric strain in sheared
      granular media increases with interparticle friction and elasticity of the
      particles. We show that the elasticity of the particles does not enhance dilation
      in frictionless granular media. The results presented here provide additional
      understanding of the role of particle-scale properties on the collective behavior
      of three-dimensional granular media subjected to shearing.

PMID- 19391937
TI  - Simulation of cohesive head-on collisions of thermally activated nanoclusters.
AB  - Impact phenomena of nanoclusters subject to thermal fluctuations are numerically
      investigated. From the molecular dynamics simulation for colliding two identical
      clusters, it is found that the restitution coefficient for head-on collisions has
      a peak at a colliding speed due to the competition between the cohesive
      interaction and the repulsive interaction of colliding clusters. Some aspects of
      the collisions can be understood by the theory of Brilliantov [Phys. Rev. E 76,
      051302 (2007)], but many aspects are found from the simulation. In particular, we
      find that there are some anomalous rebounds in which the restitution coefficient
      is larger than unity. The phase diagrams of rebound processes against impact
      speed and the cohesive parameter can be understood by a simple phenomenology.

PMID- 19391938
TI  - Short-time motion of Brownian particles in a shear flow.
AB  - The short-time motion of Brownian particles in an incompressible Newtonian fluid
      under shear, in which the fluid inertia becomes important, was investigated by
      direct numerical simulation of particulate flows. Three-dimensional simulations
      were performed, wherein external forces were introduced to approximately form
      Couette flows throughout the entire system with periodic boundary conditions. In
      order to examine the validity of the method, the mean-square displacement of a
      single spherical particle in a simple shear flow was calculated, and these
      results were compared with a hydrodynamic analytical solution that includes the
      effects of the fluid inertia. Finally, the dynamical behavior of a monodisperse
      dispersion composed of repulsive spherical particles was examined on short-time
      scales, and the shear-induced diffusion coefficients were measured for several
      volume fractions up to 0.50.

PMID- 19391939
TI  - Persistent correlation of constrained colloidal motion.
AB  - We have investigated the motion of a single optically trapped colloidal particle
      close to a limiting wall at time scales where the inertia of the surrounding
      fluid plays a significant role. The velocity autocorrelation function exhibits a
      complex interplay due to the momentum relaxation of the particle, the vortex
      diffusion in the fluid, the obstruction of flow close to the interface, and the
      harmonic restoring forces due to the optical trap. We show that already a weak
      trapping force has a significant impact on the velocity autocorrelation function
      C(t)=v(t)v(0) at times where the hydrodynamic memory leads to an algebraic decay.
      The long-time behavior for the motion parallel and perpendicular to the wall is
      derived analytically and compared to numerical results. Then, we discuss the
      power spectral densities of the displacement and provide simple interpolation
      formulas. The theoretical predictions are finally compared to recent experimental
      observations.

PMID- 19391940
TI  - Surface structure of sterically stabilized ferrofluids in a normal magnetic
      field: grazing-incidence x-ray study.
AB  - We studied the internal structure of sterically stabilized water- and oil-based
      ferrofluids in the vicinity of the free interface with a gas by means of x-ray
      reflectometry and grazing-incidence x-ray diffraction. It was found that in-depth
      distribution of the magnetic nanoparticles in the layer close to the interface is
      essentially inhomogeneous. In the case of water-based ferrofluids an enhanced
      concentration of surfactant and subsequent reduced concentration of the particles
      were detected in the 100-200-A -thick interface-adjacent layer. Scattering
      patterns possessing characteristic features of powder diffraction revealed
      partial ordering of the surfactant in a multilamellar structure. External
      magnetic fields applied perpendicular to the interface effectively reduced
      thickness of the depleted layer bringing the particles from the bulk to the
      surface. However no field-induced correlations between the particles were
      detected. In the top 500-A -thick layer of an oil-based ferrofluid depletion of
      the particles density was also present; however, no special arrangement of the
      surfactant molecules was manifested by the experimental data. Interestingly, for
      all samples we observed wavy surface deformation appearing in the normal magnetic
      field of a strength H much smaller than the critical values H_{c} calculated
      according to the conventional theory of ferrofluid surface instability. This
      deformation with lateral periodicity of a few millimeters has an amplitude
      smoothly increasing up to a few microns at H=0.5H_{c} .

PMID- 19391941
TI  - Structure and dynamics of reverse micelles containing supercooled water
      investigated by neutron scattering.
AB  - We present a detailed neutron scattering study of the structure, shape
      fluctuations, and translational diffusion of microemulsion droplets at low
      temperatures. We investigate the ternary microemulsion D2O , AOT [bis(2-ethyl
      hexyl) sulfosuccinate], and toluene-d8 (or heptane-d16) which forms spherical
      water droplets surrounded by a monolayer of AOT dispersed in oil around room
      temperature. At T=290 K , varying the molar ratio omega of water to AOT between 3
      and 12, we find using small angle neutron scattering water core radii R_{c}
      between 7 and 18 A , respectively. We characterize the structure at low
      temperatures down to T=220 K . Upon cooling the droplet structure is maintained
      and R_{c} stays roughly constant down to temperatures where the confined water is
      deeply supercooled. At an omega -dependent temperature T_{s} we observe for all
      compositions a shrinking of the droplets, which depends on the initial droplet
      size: the smaller the initial radii, the lower the T_{s} is. At the lowest
      investigated temperature T=220 K we find an omega -independent remaining water
      core corresponding to a number of about 2 water molecules per AOT molecule.
      Neutron spin-echo spectroscopy is used to monitor shape fluctuations and
      translational diffusion for one microemulsion ( omega=8 , R_{w}=12 A ) from T=300
      K down to temperatures below the corresponding shrinking temperature T_{s} .
      Thereby we determine the bending elasticity to be kappa=0.3k_{B}T over the whole
      investigated temperature range where the droplets are stable. From these results
      we cannot establish a link between surfactant membrane elasticity and low
      temperature structural instability of the droplets. Moreover, our results show
      that reverse AOT micelles are an excellent tool for the study of soft confined
      water over a broad range of confining sizes and temperatures down to the
      supercooled state.

PMID- 19391942
TI  - Test particle limit for the pair structure of quenched-annealed fluid mixtures.
AB  - A density functional route to the pair structure of quenched-annealed fluid
      mixtures is presented. The bulk two-body partial pair correlation functions of
      the mixture are identified with the one-body density distributions in an external
      potential that models a fixed test particle. Quenched-annealed (replica) density
      functional theory is used to calculate the inhomogeneous one-body density
      distributions. A closed theory is obtained by using an exact sum rule that
      equates two different expressions for the cross pair correlation function between
      unlike species. Results for binary quenched-annealed hard sphere mixtures are
      found to agree well with computer simulation data, improving over results from
      the replica Ornstein-Zernike equations using the direct correlation functions,
      obtained as second functional derivatives of the quenched-annealed excess free
      energy functional, as input. The proposed framework allows for the independent
      determination of the blocked part of the fluid-fluid partial pair correlation
      function.

PMID- 19391943
TI  - Structure of quasi-one-dimensional ribbon colloid suspensions.
AB  - We report the results of an experimental study of a colloid fluid confined to a
      quasi-one-dimensional (q1D) ribbon channel as a function of channel width and
      colloid density. Our findings confirm the principal predictions of previous
      theoretical studies of such systems. These are (1) that the density distribution
      of the liquid transverse to the ribbon channel exhibits stratification; (2) that
      even at the highest density the order along the strata, as measured by the
      longitudinal pair correlation function, is characteristic of a liquid; and (3)
      the q1D pair correlation functions in different strata exhibit anisotropic
      behavior resembling that found in a Monte Carlo simulation for the in-plane pair
      correlation function of a hard sphere fluid in a planar slit.

PMID- 19391944
TI  - Quantitative theory of a time-correlation function in a one-component glass
      forming liquid with anisotropic potential.
AB  - The Shintani-Tanaka model is a glass-forming system whose constituents interact
      via an anisotropic potential depending on the angle of a unit vector carried by
      each particle. The decay of time-correlation functions of the unit vectors
      exhibits the characteristics of generic relaxation functions during glass
      transitions. In particular it exhibits a stretched exponential form, with the
      stretching index beta depending strongly on the temperature. We construct a
      quantitative theory of this correlation function by analyzing all the physical
      processes that contribute to it, separating a rotational from a translational
      decay channel. These channels exhibit different relaxation times, each with its
      own temperature dependence. Interestingly, the separate decay function of each of
      these processes is a temperature-independent function, and is shown to scale
      (exhibit data collapse) at different temperatures. Taken together with
      temperature-dependent weights determined a priori by statistical mechanics this
      allows one to generate the observed correlation function in quantitative
      agreement with simulations at different temperatures. This underlines the danger
      of concluding anything about glassy relaxation functions without detailed
      physical scrutiny.

PMID- 19391945
TI  - Phase-field modeling of dry snow metamorphism.
AB  - Snow on the ground is a complex three-dimensional porous medium consisting of an
      ice matrix formed by sintered snow crystals and a pore space filled with air and
      water vapor. If a temperature gradient is imposed on the snow, a water vapor
      gradient in the pore space is induced and the snow microstructure changes due to
      diffusion, sublimation, and resublimation: the snow metamorphoses. The snow
      microstructure, in turn, determines macroscopic snow properties such as the
      thermal conductivity of a snowpack. We develop a phase-field model for snow
      metamorphism that operates on natural snow microstructures as observed by
      computed x-ray microtomography. The model takes into account heat and mass
      diffusion within the ice matrix and pore space, as well as phase changes at the
      ice-air interfaces. Its construction is inspired by phase-field models for alloy
      solidification, which allows us to relate the phase-field to a sharp-interface
      formulation of the problem without performing formal matched asymptotics. To
      overcome the computational difficulties created by the large difference between
      diffusional and interface-migration time scales, we introduce a method for
      accelerating the numerical simulations that formally amounts to reducing the heat
      and mass-diffusion coefficients while maintaining the correct interface
      velocities. The model is validated by simulations for simple one- and two
      dimensional test cases. Furthermore, we perform qualitative metamorphism
      simulations on natural snow structures to demonstrate the potential of the
      approach.

PMID- 19391946
TI  - Phase behavior of a reversibly assembling system in two dimensions: a Monte Carlo
      simulation study.
AB  - Using Monte Carlo simulation, we investigate the structural phase behavior of a
      continuum molecular model for self-assembling semiflexible equilibrium polymers
      in two dimensions. Particle-particle interaction is modeled via a Lennard-Jones
      potential with tunable anisotropic attraction. Depending on the strength of the
      anisotropy, we find the formation of reversible networks as well as stiff rodlike
      aggregates. The phase transition observed in the presence of the network
      structures is compared to predictions of the Tlusty-Safran defect model.

PMID- 19391947
TI  - Nonequilibrium dynamics in an amorphous solid.
AB  - The nonequilibrium dynamics of an amorphous solid is studied with a soft-spin
      model. We show that the aging behavior in the glassy state follows a modified
      Kohlrausch-Williams-Watts form similar to that obtained in Lunkenheimer [Phys.
      Rev. Lett. 95, 055702 (2005)] from analysis of the dielectric loss data. The
      nature of the fluctuation-dissipation theorem violation is also studied in time
      as well as correlation windows.

PMID- 19391948
TI  - Thermodynamics and roughening of solid-solid interfaces.
AB  - The dynamics of sharp interfaces separating two nonhydrostatically stressed
      solids is analyzed using the idea that the rate of mass transport across the
      interface is proportional to the thermodynamic potential difference across the
      interface. The solids are allowed to exchange mass by transforming one solid into
      the other, thermodynamic relations for the transformation of a mass element are
      derived and a linear stability analysis of the interface is carried out. The
      stability is shown to depend on the order of the phase transition occurring at
      the interface. Numerical simulations are performed in the nonlinear regime to
      investigate the evolution and roughening of the interface. It is shown that even
      small contrasts in the referential densities of the solids may lead to the
      formation of fingerlike structures aligned with the principal direction of the
      far field stress.

PMID- 19391949
TI  - Spontaneous motion of a droplet evolved by resonant oscillation of a vortex pair.
AB  - We studied dissipative structures in the pattern formation of self-organized flow
      inside a droplet and spontaneous motion of the droplet when two driving forces,
      mass transfer of a solute from the droplet to surrounding media and continuous
      supply of solution to the droplet, were applied. When solute concentration
      increases beyond a critical value, a jetlike flow erupts out of the droplet
      (eruption). A similar flow simultaneously enters the droplet (irruption),
      producing internal flow. The resulting internal flow develops into two vortices
      along the droplet surface. Each vortex moves in a circular orbit along the
      droplet surface by local flow due to the other vortex, while continuous solute
      eruptions occur out of the vortex pair. The entire droplet rotates slowly at the
      same velocity as the rotation of the vortex pair. The vortex pair then oscillates
      with rotation, inducing droplet wiggle with slow rotation. The vortex motion
      resembles precession accompanied by nutation of a spinning top about a fixed
      point. Temporal evolution of droplet motion describes a pattern of short waves
      superimposed on a long wave. Short waves are induced by "nutation" of the vortex
      pair, and the long wave by "precession." The amplitude of the short wave varies
      with time because of the interaction between vortices. The vortex pair acts as
      coupled oscillators. Resonance interaction can occur between the long wave and
      the envelope of short waves when the phase velocity of the long wave becomes
      equal to the group velocity of short waves, markedly changing droplet motion;
      vigorous and regular fast rotation of the droplet suddenly occurs.

PMID- 19391950
TI  - Quantitative phase-field modeling for dilute alloy solidification involving
      diffusion in the solid.
AB  - An antitrapping current scheme for quantitative phase-field model [A. Karma,
      Phys. Rev. Lett. 87, 115701 (2001)] is extended to solidification process in a
      dilute binary alloy system involving diffusion in the solid. It is demonstrated
      in an asymptotic analysis that in the case of an arbitrary value of the solid
      diffusivity, five types of constraints exist between interpolating functions used
      in the phase-field model, which need to be satisfied simultaneously to eliminate
      all anomalous interface effects. Then, the authors present an appropriate form of
      the antitrapping current term for the two-sided case to remove all the spurious
      effects. The convergence test of the output with respect to the interface
      thickness was carried out for the isothermal dendrite growth process, which
      demonstrates an excellent performance of the present model.

PMID- 19391951
TI  - Molecular-dynamics simulation of evaporation processes of fluid bridges confined
      in slitlike pores.
AB  - A simple fluid, described by pointlike particles interacting via the Lennard
      Jones potential, is considered under confinement in a slit geometry between two
      walls at distance L_{z} apart for densities inside the vapor-liquid coexistence
      curve. Equilibrium then requires the coexistence of a liquid "bridge" between the
      two walls, and vapor in the remaining pore volume. We study this equilibrium for
      several choices of the wall-fluid interaction (corresponding to the full range
      from complete wetting to complete drying, for a macroscopically thick film), and
      consider also the kinetics of state changes in such a system. In particular, we
      study how this equilibrium is established by diffusion processes, when a liquid
      is inserted into an initially empty capillary (partial or complete evaporation
      into vacuum), or when the volume available for the vapor phase increases. We
      compare the diffusion constants describing the rates of these processes in such
      inhomogeneous systems to the diffusion constants in the corresponding bulk liquid
      and vapor phases.

PMID- 19391952
TI  - Dewetting dynamics of stressed viscoelastic thin polymer films.
AB  - Ultrathin polymer films that are produced, e.g., by spin coating are believed to
      be stressed since polymers are "frozen in" into out-of-equilibrium configurations
      during this process. In the framework of a viscoelastic thin-film model, we study
      the effects of lateral residual stresses on the dewetting dynamics of the film.
      The temporal evolution of the height profiles and the velocity profiles inside
      the film as well as the dissipation mechanisms are investigated in detail. Both
      the shape of the profiles and the importance of frictional dissipation vs viscous
      dissipation inside the film are found to change in the course of dewetting. The
      interplay of the nonstationary profiles, the relaxing initial stress, and the
      changes in the dominance of the two dissipation mechanisms caused by nonlinear
      friction with the substrate is responsible for the rich behavior of the system.
      In particular, our analysis sheds a different light on the occurrence of the
      unexpected maximum in the rim width obtained recently in experiments on
      polystyrene-polydimethylsiloxane systems.

PMID- 19391953
TI  - Molecular dynamics simulations of supercritical water confined within a carbon
      slit pore.
AB  - We report the results of a series of molecular dynamics simulations of water
      inside a carbon-slit pore at supercritical conditions. A range of densities
      corresponding from liquid (0.66gcm;{-3}) to gas environments (0.08gcm;{-3}) at
      the supercritical temperature of 673K were considered. Our findings are compared
      with previous studies of liquid water confined in graphene nanochannels at
      ambient and high temperatures, and indicate that the microscopic structure of
      water evolves from hydrogen bond networks characteristic of hot dense liquids to
      looser arrangements where the dominant units are water monomers and dimers. Water
      permittivity was found to be very small at low densities, with a tendency to grow
      with density and to reach typical values of unconfined supercritical water at
      0.66gcm;{-3}) . In supercritical conditions, the residence time of water at
      interfaces is roughly similar to that of water in the central regions of the
      slabs, if the size of the considered region is taken into account. That time span
      is long enough to compute dynamical properties such as diffusion or spectral
      densities. Water diffusion in supercritical states is much faster at low
      densities, and it is produced in such a way that, at interfaces, translational
      diffusion is mainly produced along planes parallel to the carbon walls. Spectral
      frequency shifts depend on several factors, being temperature and density effects
      the most relevant. However, we can observe corrections due to confinement,
      important both at the graphene interface and in the central region of the water
      slab.

PMID- 19391954
TI  - Boundaries, kinetic properties, and final domain structure of plane discrete
      uniform Poisson-Voronoi tessellations with von Neumann neighborhoods.
AB  - Discrete random tessellations appear not infrequently in describing nucleation
      and growth transformations. Generally, several non-Euclidean metrics are possible
      in this case. Previously [A. Korobov, Phys. Rev. B 76, 085430 (2007)] continual
      analogs of such tessellations have been studied. Here one of the simplest
      discrete varieties of the Kolmogorov-Johnson-Mehl-Avrami model, namely, the model
      with von Neumann neighborhoods, has been examined per se, i.e., without
      continualization. The tessellation is uniform in the sense that domain boundaries
      consist of tiles. Similarities and distinctions between discrete and continual
      models are discussed.

PMID- 19391955
TI  - Numerical solution of the nonequilibrium square-gradient model and verification
      of local equilibrium for the Gibbs surface in a two-phase binary mixture.
AB  - In this paper we apply the general analysis described in our first paper to a
      binary mixture of cyclohexane and n -hexane. We use the square gradient model for
      the continuous description of a nonequilibrium surface and obtain numerical
      profiles of various thermodynamic quantities in various stationary state
      conditions. Details of the numerical procedure are given and discussed. In the
      second part of this paper we focus on the verification of local equilibrium of
      the surface as described with excess densities. We give a definition of the
      temperature and chemical potentials of the surface and verify that these
      quantities are independent of the choice of the dividing surface. We verify
      numerically that the surface in a stationary state of the mixture can be
      described in terms of Gibbs excess densities, which are found to be in good
      approximation equal to their equilibrium values at the stationary state
      temperature and chemical potentials of the surface.

PMID- 19391957
TI  - Theory and computer simulation for the cubatic phase of cut spheres.
AB  - The phase behavior of a system of hard-cut spheres has been studied using a high
      order virial theory and by Monte Carlo simulation. The cut-sphere particles are
      disks of thickness L formed by symmetrically truncating the end caps of a sphere
      of diameter D . The virial theory predicts a stable nematic phase for aspect
      ratio LD=0.1 and a stable cubatic phase for LD=0.15-0.3 . The virial series
      converges rapidly on the equation of state of the isotropic and nematic phases,
      while for the cubatic phase the convergence is slower, but still gives good
      agreement with the simulation at high order. It is found that a high-order
      expansion (up to B8 ) is required to predict a stable cubatic phase for LD> or
      =0.15 , indicating the importance of many-body interactions in stabilizing this
      phase. Previous simulation work on this system has focused on aspect ratios
      LD=0.1 , 0.2, and 0.3. We expand this to include also LD=0.15 and 0.25, and we
      introduce a fourth-rank tensor to measure cubatic ordering. We have applied a
      multiparticle move which dramatically speeds the attainment of equilibrium in the
      nematic phase and therefore is of great benefit in the study of the isotropic
      nematic phase transition. In agreement with the theory, our simulations confirm
      the stability of the nematic phase for LD=0.1 and the stability of the cubatic
      phase over the nematic for LD=0.15-0.3 . There is, however, some doubt about the
      stability of the cubatic phase with respect to the columnar. We have shown that
      the cubatic phase found on compression at LD=0.1 is definitely metastable, but
      the results for LD=0.2 were less conclusive.

PMID- 19391956
TI  - Relaxational dynamics of smectic phases on a curved substrate.
AB  - We study the dynamics of pattern formation of two-dimensional smectic systems
      constrained to lie on a substrate with sinusoidal topography. We observe a
      coupling between defects and geometry that induces the preferential location of
      positive (negative) defects onto regions with positive (negative) Gaussian
      curvature. For the curvatures studied here we observe unbinding and self
      organization of disclination pairs. The local orientation of the pattern and the
      location of topological defects can be accurately controlled with the curvature
      of the underlying substrate. Thus, long-range interactions arising from the
      geometry of the substrate lead to ordered patterns with potential applications to
      nanotechnology.

PMID- 19391958
TI  - Smectic- A and - C phases, and the transition between them, in uniaxial
      disordered environments.
AB  - We present a theory of the elasticity and fluctuations of the smectic- A and - C
      phases in uniaxial, anisotropic disordered environments: e.g., stretched aerogel.
      We find that, bizarrely, the low-temperature, lower-symmetry smectic- C phase is
      less translationally ordered than the high-temperature, higher-symmetry smectic-
      A phase, with short-range " m=1 Bragg glass" and algebraic " XY Bragg glass"
      order, respectively. The smectic- A -smectic- C (AC) phase transition belongs to
      a new universality class, whose fixed points and exponents we find in a d=5-
      expansion. We give very detailed predictions for the very rich light-scattering
      behavior of both phases and the critical point.

PMID- 19391959
TI  - Surface-induced ordering effect in one antiferroelectric liquid crystal compound.
AB  - Null transmission ellipsometer was employed to study the surface-induced tilt
      transition of an antiferroelectric liquid crystal compound in the bulk smectic- A
      (SmA) temperature range. The data of the surface tilt transition can be fitted
      with an extended mean-field model. These results indicate the transition is near
      a mean-field tricritical point. The surface layers' tilt directions are found to
      be in different planes several degrees above the bulk SmA-SmC_{alpha};{ *}
      transition.

PMID- 19391960
TI  - Effect of the network density on dynamics of the soft and the Goldstone modes in
      short-pitch ferroelectric liquid crystals stabilized by an anisotropic polymer
      network.
AB  - We report the influence of the polymer network density formed in short-pitch
      ferroelectric liquid crystal (FLC) on the soft and the Goldstone dielectric
      relaxation modes. The experimental results of the pure FLC and the FLC stabilized
      by a polymer network with various densities are presented and compared. These
      results reveal that in the SmC;{ *} phase, when the polymer concentration
      increases, the Goldstone dielectric strength gradually decreases and the
      relaxation frequency is shifted to higher values. In the SmA;{ *} phase, the
      results show that close to the SmC;{ *}-SmA;{ *} transition temperature, T_{c} ,
      the soft relaxation mode is largely influenced by the polymer network: a sharp
      decrease in the dielectric strength and an increase in the relaxation frequency
      when the polymer density increases were observed. The soft mode is relatively
      weakly affected by the network for higher temperatures (T> or =T_{c}+0.5 degrees
      C) . This indicates that the behavior of the soft mode for this temperature
      domain is dominated rather by thermal effects than by the network. A simple
      phenomenological approach was proposed to explain the behavior of the soft-mode
      dielectric strength versus polymer concentration. This model takes into account
      the anisotropic interaction between the polymer network and the liquid crystal,
      and the elastic interaction resulting from the anchoring of the liquid crystal
      molecules at the polymer surfaces. The experimental results are in agreement with
      the proposed model.

PMID- 19391961
TI  - Time-resolved x-ray studies of the dynamics of smectic- A layer realignment by
      magnetic fields.
AB  - While the rotation of smectic layers under an applied field may at first appear
      to be a relatively simple problem, the dynamic processes involved are rather
      complex. An applied field produces a torque on the liquid crystal director, but
      has no direct influence on the smectic layers. If the director is reoriented
      significantly, however, the layers must also reorient in order to accommodate
      this (the layered structure is produced by short-range molecular interactions).
      Indeed, if the liquid crystalline order is not maintained during the realignment
      then matters become even more complex. In this paper we use time-resolved x-ray
      scattering to investigate the realignment of smectic- A layers in thin-film
      devices using a magnetic field. No evidence is found for continuous rotation of
      the smectic layers under any circumstances in such devices, a result that is not
      found when using bulk samples. No evidence indicating the formation of the
      nematic phase is observed during realignment. A molecular-dynamics technique is
      used to model the system which indicates that the sample becomes significantly
      disorganized during the realignment process when large angular rotations are
      induced.

PMID- 19391962
TI  - Tightening of the elastic overhand knot.
AB  - The process of tightening of the open trefoil knot tied on an elastic filament is
      analyzed. Evolution of the curvature profile is presented and discussed.

PMID- 19391963
TI  - Theory and computation of photopolymerization-induced phase transition and
      morphology development in blends of crystalline polymer and photoreactive
      monomer.
AB  - A hypothetical phase diagram of a crystalline polymer/photoreactive monomer
      mixture has been calculated on the basis of phase field (PF) free energy of
      crystal solidification in conjunction with Flory-Huggins (FH) free energy of
      liquid-liquid demixing to guide the morphology development during
      photopolymerization of poly(ethylene oxide)/triacrylate blend. The self
      consistent solution of the combined PF-FH theory exhibits a crystalline-amorphous
      phase diagram showing the coexistence of solid+liquid gap bound by the liquidus
      and solidus lines, followed by an upper critical solution temperature at a lower
      temperature. When photopolymerization was triggered in the isotropic region,
      i.e., slightly above the crystal melting transition temperatures, the depressed
      melting transition line moves upward. When it surpasses the reaction temperature,
      both crystallization and phase separation occur. The temporal evolution of phase
      morphology is examined in the context of time-dependent Ginzburg-Landau equations
      coupled with the energy balance (heat conduction) equation using the
      aforementioned PF-FH free-energy densities. Of particular interest is that the
      emerged morphology in the crystalline blends depends on the competition between
      dynamics of liquid-liquid phase separation and/or liquid-solid phase transition
      (i.e., crystallization) and photopolymerization rates.

PMID- 19391964
TI  - Dynamical self-arrest in symmetric and asymmetric diblock copolymer melts using a
      replica approach within a local theory.
AB  - We investigate dynamical self-arrest in a diblock copolymer melt using a replica
      approach within a self-consistent local method based on dynamical mean-field
      theory (DMFT). The local replica approach effectively predicts (chiN)_{A} for
      dynamical self-arrest in a block copolymer melt for symmetric and asymmetric
      cases. We discuss the competition of the cubic and quartic interactions in the
      Landau free energy for a block copolymer melt in stabilizing a glassy state
      depending on the chain length. Our local replica theory provides a universal
      value for the dynamical self-arrest in block copolymer melts with (chiN)_{A}
      approximately 10.5+64N;{-3/10} for the symmetric case.

PMID- 19391965
TI  - Asymmetric charge renormalization for nanoparticles in aqueous media.
AB  - The effective renormalized charge of nanoparticles in an aqueous electrolyte is
      essential to determine their solubility. By using a molecular model for the
      supporting aqueous electrolyte, we find that the effective renormalized charge of
      the nanoparticles is strongly dependent on the sign of the bare charge.
      Negatively charged nanoparticles have a lower effective renormalized charge than
      positively charged nanoparticles. The degree of asymmetry is a nonmonotonic
      function of the bare charge of the nanoparticle. We show that the effect is due
      to the asymmetric charge distribution of the water molecules, which we model
      using a simple three-site molecular structure of point charges.

PMID- 19391967
TI  - How adsorption influences DNA denaturation.
AB  - The thermally induced denaturation of DNA in the presence of an attractive solid
      surface is studied. The two strands of DNA are modeled via two coupled flexible
      chains without volume interactions. If the two strands are adsorbed on the
      surface, the denaturation phase transition disappears. Instead, there is a smooth
      crossover to a weakly naturated state. Our second conclusion is that even when
      the interstrand attraction alone is too weak for creating a naturated state at
      the given temperature and also when the surface-strand attraction alone is too
      weak for creating an adsorbed state, the combined effect of the two attractions
      can lead to a naturated and adsorbed state.

PMID- 19391966
TI  - Interlinked dual-time feedback loops can enhance robustness to stochasticity and
      persistence of memory.
AB  - Multiple interlinked positive feedback loops shape the stimulus responses of
      various biochemical systems, such as the cell cycle or intracellular Ca2+
      release. Recent studies with simplified models have identified two advantages of
      coupling fast and slow feedback loops. This dual-time structure enables a fast
      response while enhancing resistances of responses and bistability to stimulus
      noise. We now find that (1) the dual-time structure similarly confers resistance
      to internal noise due to molecule number fluctuations, and (2) model variants
      with altered coupling, which better represent some specific biochemical systems,
      share all the above advantages. We also develop a similar bistable model with
      coupling of a fast autoactivation loop to a slow loop. This model's topology was
      suggested by positive feedback proposed to play a role in long-term synaptic
      potentiation (LTP). The advantages of fast response and noise resistance are also
      present in this autoactivation model. Empirically, LTP develops resistance to
      reversal over approximately 1h . The model suggests this resistance may result
      from increased amounts of synaptic kinases involved in positive feedback.

PMID- 19391968
TI  - Ion specific effects on phase transitions in protein solutions.
AB  - A recent Monte Carlo simulation determined the potential of mean force between
      two lysozyme molecules in various aqueous solutions [M. Lund, Phys. Rev. Lett.
      100, 258105 (2008)]. The study involved a combination of explicit solvent and
      continuum model simulations and showed that there are significant ion-specific
      protein-protein interactions due to hydrophobic patches on the protein surfaces.
      In this paper we use the results of their study to determine the phase diagram
      for lysozyme for aqueous solutions of NaCl and NaI. Two of the three phase
      diagrams have a stable fluid-fluid critical point, while the third has a slightly
      metastable critical point. This results from a secondary extremum in the
      potential associated with a repulsive interaction. This repulsive interaction
      reduces the effective range of the attractive interaction and produces a
      metastable critical point. We compare the results of one of these phase diagrams
      with that for a model that includes ion-dispersion forces, but does not contain
      solvent structural effects.

PMID- 19391969
TI  - Compatibility between itinerant synaptic receptors and stable postsynaptic
      structure.
AB  - The density of synaptic receptors in front of presynaptic release sites is
      stabilized in the presence of scaffold proteins, but the receptors and scaffold
      molecules have local exchanges with characteristic times shorter than that of the
      receptor-scaffold assembly. We propose a mesoscopic model to account for the
      regulation of the local density of receptors as quasiequilibrium. It is based on
      two zones (synaptic and extrasynaptic) and multilayer (membrane, submembrane, and
      cytoplasmic) topological organization. The model includes the balance of chemical
      potentials associated with the receptor and scaffold protein concentrations in
      the various compartments. The model shows highly cooperative behavior including a
      "phase change" resulting in the formation of well-defined postsynaptic domains.
      This study provides theoretical tools to approach the complex issue of synaptic
      stability at the synapse, where receptors are transiently trapped yet rapidly
      diffuse laterally on the plasma membrane.

PMID- 19391970
TI  - Kinetics of signaling-DNA-aptamer-ATP binding.
AB  - DNA aptamers are molecular biosensors consisting of single functionalized DNA
      molecules, which can bind to specific targets or complementary DNA sequences. The
      binding kinetics of DNA aptamers is studied by fluorescence quenching at 23
      degrees C . A kinetic model for the binding reaction of DNA aptamer, antisense
      DNA, and ATP target is developed to describe experimental observations. The
      approach leads to a simple procedure to deduce relevant kinetic reactions and
      their rate constants. A comparison between theory and experiments indicates that
      the previously established bimolecular DNA-ATP binding does not provide a
      complete description of the experimental data. Side reactions such as
      trimolecular complexation are proposed. Rate constants of the model are
      determined by comparing the model predictions and experiments. Good agreements
      between the model and experiments have been obtained. Possible blocking reactions
      by the misfolded DNA aptamer are also discussed.

PMID- 19391971
TI  - Spontaneous emergence of modularity in a model of evolving individuals and in
      real networks.
AB  - We investigate the selective forces that promote the emergence of modularity in
      nature. We demonstrate the spontaneous emergence of modularity in a population of
      individuals that evolve in a changing environment. We show that the level of
      modularity correlates with the rapidity and severity of environmental change. The
      modularity arises as a synergistic response to the noise in the environment in
      the presence of horizontal gene transfer. We suggest that the hierarchical
      structure observed in the natural world may be a broken symmetry state, which
      generically results from evolution in a changing environment. To support our
      results, we analyze experimental protein interaction data and show that protein
      interaction networks became increasingly modular as evolution proceeded over the
      last four billion years. We also discuss a method to determine the divergence
      time of a protein.

PMID- 19391972
TI  - Modeling the skin pattern of fishes.
AB  - Complicated patterns showing various spatial scales have been obtained in the
      past by coupling Turing systems in such a way that the scales of the independent
      systems resonate. This produces superimposed patterns with different length
      scales. Here we propose a model consisting of two identical reaction-diffusion
      systems coupled together in such a way that one of them produces a simple Turing
      pattern of spots or stripes, and the other traveling wave fronts that eventually
      become stationary. The basic idea is to assume that one of the systems becomes
      fixed after some time and serves as a source of morphogens for the other system.
      This mechanism produces patterns very similar to the pigmentation patterns
      observed in different species of stingrays and other fishes. The biological
      mechanisms that support the realization of this model are discussed.

PMID- 19391973
TI  - Very long transients, irregular firing, and chaotic dynamics in networks of
      randomly connected inhibitory integrate-and-fire neurons.
AB  - We present results of an extensive numerical study of the dynamics of networks of
      integrate-and-fire neurons connected randomly through inhibitory interactions. We
      first consider delayed interactions with infinitely fast rise and decay.
      Depending on the parameters, the network displays transients which are short or
      exponentially long in the network size. At the end of these transients, the
      dynamics settle on a periodic attractor. If the number of connections per neuron
      is large ( approximately 1000) , this attractor is a cluster state with a short
      period. In contrast, if the number of connections per neuron is small (
      approximately 100) , the attractor has complex dynamics and very long period.
      During the long transients the neurons fire in a highly irregular manner. They
      can be viewed as quasistationary states in which, depending on the coupling
      strength, the pattern of activity is asynchronous or displays population
      oscillations. In the first case, the average firing rates and the variability of
      the single-neuron activity are well described by a mean-field theory valid in the
      thermodynamic limit. Bifurcations of the long transient dynamics from
      asynchronous to synchronous activity are also well predicted by this theory. The
      transient dynamics display features reminiscent of stable chaos. In particular,
      despite being linearly stable, the trajectories of the transient dynamics are
      destabilized by finite perturbations as small as O(1/N) . We further show that
      stable chaos is also observed for postsynaptic currents with finite decay time.
      However, we report in this type of network that chaotic dynamics characterized by
      positive Lyapunov exponents can also be observed. We show in fact that chaos
      occurs when the decay time of the synaptic currents is long compared to the
      synaptic delay, provided that the network is sufficiently large.

PMID- 19391974
TI  - Compression of random coils due to macromolecular crowding.
AB  - The conformation of a linear polymer chain is studied as a function of the
      concentration of a macromolecular crowding agent by neutron scattering. Excluded
      volume to random coil due to macromolecular crowding in cells is predicted to
      exert a compressive force that will tend to reduce its size. It is shown that
      when reducing free volume due to macromolecular crowding, we observe a
      compression of the polymer chain with a reduction in its radius of gyration of up
      to approximately 30% and that the effective chain-chain interactions are strongly
      modified.

PMID- 19391975
TI  - Stochasticity of gene products from transcriptional pulsing.
AB  - Transcriptional pulsing has been observed in both prokaryotes and eukaryotes and
      plays a crucial role in cell-to-cell variability of protein and mRNA numbers. An
      important issue is how the time constants associated with episodes of
      transcriptional bursting and mRNA and protein degradation rates lead to different
      cellular mRNA and protein distributions, starting from the transient regime
      leading to the steady state. We address this by deriving and then investigating
      the exact time-dependent solution of the master equation for a transcriptional
      pulsing model of mRNA distributions. We find a plethora of results. We show that,
      among others, bimodal and long-tailed (power-law) distributions occur in the
      steady state as the rate constants are varied over biologically significant time
      scales. Since steady state may not be reached experimentally we present results
      for the time evolution of the distributions. Because cellular behavior is
      determined by proteins, we also investigate the effect of the different mRNA
      distributions on the corresponding protein distributions using numerical
      simulations.

PMID- 19391976
TI  - Pulling self-interacting polymers in two dimensions.
AB  - We investigate a two-dimensional problem of an isolated self-interacting end
      grafted polymer, pulled by one end. In the thermodynamic limit, we find that the
      model has only two different phases, namely a collapsed phase and a stretched
      phase. We show that the phase diagram obtained by Kumar [Phys. Rev. Lett. 98,
      128101 (2007)] for small systems, where differences between various statistical
      ensembles play an important role, differs from the phase diagram obtained here in
      the thermodynamic limit.

PMID- 19391977
TI  - Fractal properties of lysozyme: a neutron scattering study.
AB  - The spatial structure and dynamics of hen egg white lysozyme have been
      investigated by small-angle and inelastic neutron scattering. Analysis of the
      results was carried using the fractal approach, which allowed determination of
      the fractal and fracton dimensions of lysozyme, i.e., consideration of the
      protein structure and dynamics by using a unified approach. Small-angle neutron
      scattering studies of thermal denaturation of lysozyme have revealed changes in
      the fractal dimension in the vicinity of the thermal denaturation temperature
      that reflect changes in the spatial organization of protein.

PMID- 19391979
TI  - Relaxation dynamics of fluid membranes.
AB  - We study the effect of membrane viscosity in the dynamics of liquid membranes
      possibly with free or internal boundaries-driven by conservative forces
      (curvature elasticity and line tension) and dragged by the bulk dissipation of
      the ambient fluid and the friction occurring when the amphiphilic molecules move
      relative to each other. To this end, we formulate a continuum model which
      includes a form of the governing equations for a two-dimensional viscous fluid
      moving on a curved, time-evolving surface. The effect of membrane viscosity has
      received very limited attention in previous continuum studies of the dynamics of
      fluid membranes, although recent coarse-grained discrete simulations suggest its
      importance. By applying our model to the study of vesiculation and membrane
      fusion in a simplified geometry, we conclude that membrane viscosity plays a
      dominant role in the relaxation dynamics of fluid membranes of sizes comparable
      to those found in eukaryotic cells, and is not negligible in many large synthetic
      systems of current interest.

PMID- 19391978
TI  - Nonequilibrium actin polymerization treated by a truncated rate-equation method.
AB  - Actin polymerization time courses can exhibit rich nonequilibrium dynamics that
      have not yet been accurately described by simplified rate equations.
      Sophisticated stochastic simulations and elaborate recursion schemes have been
      used to model the nonequilibrium dynamics resulting from the hydrolysis and
      subsequent exchange of the nucleotide bound within the actin molecules. In this
      work, we use a truncation approach to derive a set of readily accessible
      deterministic rate equations which are significantly simpler than previous
      attempts at such modeling. These equations may be incorporated into whole-cell
      motility models which otherwise quickly become computationally inaccessible if
      polymerization of individual actin filaments is stochastically simulated within a
      virtual cell. Our equations accurately predict the relative concentrations of
      both monomeric and polymerized actin in differing nucleotide hydrolysis states
      throughout entire polymerization time courses nucleated via seed filaments. We
      extend our model to include the effects of capping protein. We also detail how
      our rate-equation method may be used to extract key parameters from experimental
      data.

PMID- 19391980
TI  - Buckling-induced zebra stripe patterns in nematic F-actin.
AB  - Rather than forming a simple and uniform nematic liquid crystal, concentrated
      solutions of semiflexible polymers, such as F-actin, have been observed to
      display a spatially periodic switching of the nematic director. When observed
      with polarization microscopy, these patterns appear as alternating light and dark
      bands, often referred to as zebra stripe patterns. Zebra stripe patterns,
      although not fully characterized, are due to periodic orientation distortions in
      the nematic order. We characterize such patterns by using a combination of two
      techniques. Using polarization microscopy, we quantify the periodic orientation
      distortions and show that the magnitude of the order parameter also varies
      periodically in the striped domains. When using fluorescently labeled filaments
      as markers, filaments spanning the striped domains are seen to undergo large
      angle bends. With fluorescence, clear density differences between adjacent
      stripes are also observed with domains of lesser density corresponding to
      strongly bent filaments. By directly comparing patterned areas with both
      polarization and fluorescence techniques, we show that periodic variation in the
      orientation, order parameter, filament bending, and density are correlated. We
      propose that these effects originate from the coupling of orientation and density
      that occurs for highly concentrated solutions of long semiflexible polymers
      subject to shear flows, as previously proposed [P. de Gennes, Mol. Cryst. Liq.
      Cryst. (Phila. Pa.) 34, 177 (1977)]. After cessation of shearing, strong
      interfilament interactions and high compressibility can lead to periodic buckling
      from the relaxation of filaments stretched during flows. The characterization of
      zebra stripe patterns presented here provides evidence that buckling in confined
      F-actin nematics produces strong periodic bending that is responsible for the
      observed features.

PMID- 19391981
TI  - Modeling tumor cell migration: From microscopic to macroscopic models.
AB  - It has been shown experimentally that contact interactions may influence the
      migration of cancer cells. Previous works have modelized this thanks to
      stochastic, discrete models (cellular automata) at the cell level. However, for
      the study of the growth of real-size tumors with several million cells, it is
      best to use a macroscopic model having the form of a partial differential
      equation (PDE) for the density of cells. The difficulty is to predict the effect,
      at the macroscopic scale, of contact interactions that take place at the
      microscopic scale. To address this, we use a multiscale approach: starting from a
      very simple, yet experimentally validated, microscopic model of migration with
      contact interactions, we derive a macroscopic model. We show that a diffusion
      equation arises, as is often postulated in the field of glioma modeling, but it
      is nonlinear because of the interactions. We give the explicit dependence of
      diffusivity on the cell density and on a parameter governing cell-cell
      interactions. We discuss in detail the conditions of validity of the
      approximations used in the derivation, and we compare analytic results from our
      PDE to numerical simulations and to some in vitro experiments. We notice that the
      family of microscopic models we started from includes as special cases some
      kinetically constrained models that were introduced for the study of the physics
      of glasses, supercooled liquids, and jamming systems.

PMID- 19391982
TI  - Using a mathematical model of cadherin-based adhesion to understand the function
      of the actin cytoskeleton.
AB  - The actin cytoskeleton plays a role in cell-cell adhesion but its specific
      function is not clear. Actin might anchor cadherins or drive membrane protrusions
      in order to facilitate cell-cell adhesion. Using a mathematical model of the
      forces involved in cadherin-based adhesion, we investigate its possible
      functions. The immersed boundary method is used to model the cell membrane and
      cortex with cadherin binding forces added as linear springs. The simulations
      indicate that cells in suspension can develop normal cell-cell contacts without
      actin-based cadherin anchoring or membrane protrusions. The cadherins can be
      fixed in the membrane or free to move, and the end results are similar. For
      adherent cells, simulations suggest that the actin cytoskeleton must play an
      active role for the cells to establish cell-cell contact regions similar to those
      observed in vitro.

PMID- 19391983
TI  - Monte Carlo simulation for statistical mechanics model of ion-channel
      cooperativity in cell membranes.
AB  - Voltage-gated ion channels are key molecules for the generation and propagation
      of electrical signals in excitable cell membranes. The voltage-dependent
      switching of these channels between conducting and nonconducting states is a
      major factor in controlling the transmembrane voltage. In this study, a
      statistical mechanics model of these molecules has been discussed on the basis of
      a two-dimensional spin model. A new Hamiltonian and a new Monte Carlo simulation
      algorithm are introduced to simulate such a model. It was shown that the results
      well match the experimental data obtained from batrachotoxin-modified sodium
      channels in the squid giant axon using the cut-open axon technique.

PMID- 19391984
TI  - Pathlines in exclusion processes.
AB  - Trajectory data from observations of a random-walk process are often used to
      characterize macroscopic transport coefficients and to make inferences about
      motility mechanisms. Continuum equations describing the average moments of the
      position of an agent in an exclusion process are derived and validated with
      simulation data. Unlike standard noninteracting random walks, the moment
      equations for the exclusion process explicitly represent the interaction of
      agents since they depend on the averaged macroscopic agent density. Key issues
      associated with the validity of the continuum equations and interpretation of
      experimental data are discussed.

PMID- 19391985
TI  - Global coupling in excitable media provides a simplified description of
      mechanoelectrical feedback in cardiac tissue.
AB  - Cardiac mechanoelectric feedback can play an important role in different heart
      pathologies. In this paper, we show that mechanoelectric models which describe
      both the electric propagation and the mechanic contraction of cardiac tissue
      naturally lead to close systems of equations with global coupling among the
      variables. This point is exemplified using the Nash-Panfilov model, which reduces
      to a FitzHugh-Nagumo-type equation with global coupling in the linear elastic
      regime. We explain the appearance of self-oscillatory regimes in terms of the
      system nullclines and describe the different dynamical attractors. Finally, we
      study their basin of attraction in terms of the system size and the strength of
      the stretch-induced currents.

PMID- 19391986
TI  - Stochastic model for nucleosome sliding under an external force.
AB  - Heat-induced diffusion of nucleosomes along DNA is an experimentally well-studied
      phenomenon, presumably induced by twist defects that propagate through the
      wrapped DNA portion. The diffusion constant depends dramatically on the local
      mechanical properties of the DNA and the presence of DNA-binding ligands. This
      has been quantitatively understood by a stochastic three-state model. Future
      experiments are expected to allow application of forces on the nucleosome that
      induce a directed sliding. By extending the three-state model, the present work
      studies theoretically the response of the nucleosome to such external forces and
      how it is affected by the mechanical properties of the DNA and the presence of
      DNA-binding ligands.

PMID- 19391987
TI  - Statistical physics of a model binary genetic switch with linear feedback.
AB  - We study the statistical properties of a simple genetic regulatory network that
      provides heterogeneity within a population of cells. This network consists of a
      binary genetic switch in which stochastic flipping between the two switch states
      is mediated by a "flipping" enzyme. Feedback between the switch state and the
      flipping rate is provided by a linear feedback mechanism: the flipping enzyme is
      only produced in the on switch state and the switching rate depends linearly on
      the copy number of the enzyme. This work generalizes the model of Visco [Phys.
      Rev. Lett. 101, 118104 (2008)] to a broader class of linear feedback systems. We
      present a complete analytical solution for the steady-state statistics of the
      number of enzyme molecules in the on and off states, for the general case where
      the enzyme can mediate flipping in either direction. For this general case we
      also solve for the flip time distribution, making a connection to first passage
      and persistence problems in statistical physics. We show that the statistics are
      non-Poissonian, leading to a peak in the flip time distribution. The occurrence
      of such a peak is analyzed as a function of the parameter space. We present a
      relation between the flip time distributions measured for two relevant choices of
      initial condition. We also introduce a correlation measure and use this to show
      that this model can exhibit long-lived temporal correlations, thus providing a
      primitive form of cellular memory. Motivated by DNA replication as well as by
      evolutionary mechanisms involving gene duplication, we study the case of two
      switches in the same cell. This results in correlations between the two switches;
      these can be either positive or negative depending on the parameter regime.

PMID- 19391988
TI  - Solution synchrotron x-ray diffraction reveals structural details of lipid
      domains in ternary mixtures.
AB  - The influence of cholesterol on lipid bilayer structure is significant and the
      effect of cholesterol on lipid sorting and phase separation in lipid-raft-forming
      model membrane systems has been well investigated by microscopy methods on giant
      vesicles. An important consideration however is the influence of fluorescence
      illumination on the phase state of these lipids and this effect must be carefully
      minimized. In this paper, we show that synchrotron x-ray scattering on solution
      lipid mixtures is an effective alternative technique for the identification and
      characterization of the l_{o} (liquid ordered) and l_{d} (liquid disordered)
      phases. The high intensity of synchrotron x rays allows the observation of up to
      5 orders of diffraction from the l_{o} phase, whereas only two are clearly
      visible when the l_{d} phase alone is present. This data can be collected in
      approximately 1 min/sample , allowing rapid generation of phase data. In this
      paper, we measure the lamellar spacing in both the liquid-ordered and liquid
      disordered phases simultaneously, as a function of cholesterol concentration in
      two different ternary mixtures. We also observe evidence of a third gel-phaselike
      population at 10-12 mol % cholesterol and determine the thickness of the bilayer
      for this phase. Importantly we are able to look at phase coexistence in the
      membrane independent of photoeffects.

PMID- 19391989
TI  - Effect of the ordered water on protein folding: an off-lattice Go-like model
      study.
AB  - Recent experiments and numerical simulations have shown that the water molecules
      confined on the surfaces of some substrates, including the surfaces of cellular
      components in tissues and cells, form icelike ordered structures. If a protein
      folds in an environment with those icelike ordered water molecules, its behavior
      may be different from that in bulk water. Here, the effect of this ordered water
      environment on protein folding is studied by using an off-lattice Go-like model.
      It is found that the ordered water environment significantly improves the native
      state stability and greatly speeds up the folding rate of the proteins.

PMID- 19391990
TI  - Phase-field modeling of the dynamics of multicomponent vesicles: Spinodal
      decomposition, coarsening, budding, and fission.
AB  - We develop a thermodynamically consistent phase-field model to simulate the
      dynamics of multicomponent vesicles. The model accounts for bending stiffness,
      spontaneous curvature, excess (surface) energy, and a line tension between the
      coexisting surface phases. Our approach is similar to that recently used by Wang
      and Du [J. Math. Biol. 56, 347 (2008)] with a key difference. Here, we
      concentrate on the dynamic evolution and solve the surface mass conservation
      equation explicitly; this equation was not considered by Wang and Du. The
      resulting fourth-order strongly coupled system of nonlinear nonlocal equations
      are solved numerically using an adaptive finite element numerical method.
      Although the system is valid for three dimensions, we limit our studies here to
      two dimensions where the vesicle is a curve. Differences between the spontaneous
      curvatures and the bending rigidities of the surface phases are found numerically
      to lead to the formation of buds, asymmetric vesicle shapes and vesicle fission
      even in two dimensions. In addition, simulations of configurations far from
      equilibrium indicate that phase separation via spinodal decomposition and
      coarsening not only affect the vesicle shape but also that the vesicle shape
      affects the phase separation dynamics, especially the coarsening and may lead to
      lower energy states than might be achieved by evolving initially phase-separated
      configurations.

PMID- 19391991
TI  - Mechanisms of proton transfer in proteins: localized charge transfer versus
      delocalized soliton transfer.
AB  - Proton translocation coupled to redox chemistry is ubiquitous for membrane
      enzymes involved in energy generation in cells. In such enzymes, proton transport
      occurs in special proton conducting channels, which consist of a series of
      protonatable groups of the protein connected by chains of mobile water molecules.
      Here we discuss two possible mechanisms of proton transport along such
      structures: diffusion of a localized charge and delocalized soliton transitions,
      in which several protons are collectively shifted along a chain of hydrogen
      bonds.

PMID- 19391992
TI  - DNA unhooking from a single post as a deterministic process: insights from
      translocation modeling.
AB  - Using stochastic methods developed for DNA translocation through nanopores, we
      study the unhooking of a long DNA chain from an isolated stationary micropost.
      Such methods quickly and efficiently furnish both the full probability
      distribution of the unhooking time and the ensuing moments for a wide range of
      chain and field parameters. The results compare favorably to more realistic but
      computationally intense Brownian dynamics simulations. For typical chain lengths
      and applied electric fields used in experiments, the unhooking process is
      effectively deterministic; diffusive fluctuations make a negligible contribution
      to the first and second moments of the unhooking time. This result lends credence
      to continuous-time random-walk models of the overall transport process that treat
      the unhooking as a convective process.

PMID- 19391994
TI  - Stretching of a single-stranded DNA: evidence for structural transition.
AB  - Recent experiments have shown that the force-extension (F-x) curve for single
      stranded DNA (ssDNA) consisting only of adenine [poly(dA)] is significantly
      different from thymine [poly(dT)]. Here, we show that the base stacking
      interaction is not sufficient to describe the F-x curves as seen in the
      experiments. A reduction in the reaction coordinate arising from the formation of
      helix at low forces and an increase in the distance between consecutive
      phosphates of unstacked bases in the stretched state at high force in the
      proposed model qualitatively reproduce the experimentally observed features. The
      multistep plateau in the F-x curve is a signature of structural change in ssDNA.

PMID- 19391993
TI  - Collective dynamics of kinesin.
AB  - Motor proteins are biological enzymes that convert chemical energy to mechanical
      work in cells. Kinesin-1 is a motor protein that transports vesicles along
      microtubules and is widely believed to be responsible for anterograde transport
      of synaptic vesicles in neurons. Advances in single-molecule techniques have
      shown that single kinesin motors are capable of processive movement along the
      microtubule at a maximum velocity of approximately 1 microm/s . The velocity
      decreases roughly linearly in response to load until reaching stall at a load of
      approximately 6 pN. Several theoretical models have been proposed that describe
      the steady-state motion of single kinesin motors. Growing evidence suggests that
      kinesin functions collectively in cells, whereby several motors work in a
      coordinated manner to transport a vesicle. A transient description is required to
      describe collective dynamics, as the interactions among coupled motors induce
      time-varying forces on each motor. Herein a mechanistic model of kinesin is
      proposed that is capable of accurately describing transient and steady-state
      dynamics. Each domain of the protein is modeled via a mechanical potential. The
      mechanical potentials are related explicitly to the chemical kinetics of each
      motor domain. The mechanistic model was used to simulate the collective behavior
      of coupled kinesin motors under varying loads, cargo linker stiffnesses, and
      numbers of motors. To analyze the simulations of coordinated transport, several
      metrics were developed that are specifically tailored to characterizing the
      synchronization of nonlinear nonsmooth oscillators such as kinesin. The model
      results suggest that, in the cell, the dynamics of coupled motors under low loads
      are loosely correlated. When the load is increased, such as when the cargo
      encounters an obstacle such as another vesicle or the cytoskeleton, motors become
      more correlated in response to increased loads, allowing them to produce greater
      forces. Increasing the number of motors involved in the transport does not
      appreciably increase the dimension of the trajectory, implying large numbers of
      motors are able to function in a highly correlated manner without becoming fully
      synchronized.

PMID- 19391995
TI  - Anomalous diffusion as modeled by a nonstationary extension of Brownian motion.
AB  - If the mean-square displacement of a stochastic process is proportional to
      t;{beta} , beta not equal1 , then it is said to be anomalous. We construct a
      family of Markovian stochastic processes with independent nonstationary
      increments and arbitrary but a priori specified mean-square displacement. We
      label the family as an extended Brownian motion and show that they satisfy a
      Langevin equation with time-dependent diffusion coefficient. If the time
      derivative of the variance of the process is homogeneous, then by computing the
      fractal dimension it can be shown that the complexity of the family is the same
      as that of the Brownian motion. For two particles initially separated by a
      distance x , the finite-size Lyapunov exponent (FSLE) measures the average rate
      of exponential separation to a distance ax . An analytical expression is
      developed for the FSLEs of the extended Brownian processes and numerical examples
      presented. The explicit construction of these processes illustrates that contrary
      to what has been stated in the literature, a power-law mean-square displacement
      is not necessarily related to a breakdown in the classical central limit theorem
      (CLT) caused by, for example, correlation (fractional Brownian motion or
      correlated continuous-time random-walk schemes) or infinite variance (Levy
      motion). The classical CLT, coupled with nonstationary increments, can and often
      does give rise to power-law moments such as the mean-square displacement.

PMID- 19391996
TI  - Contact-line speed and morphology in vertical deposition of diluted colloids.
AB  - We report experimental results on the speed of a receding contact line, in a
      vertical deposition configuration, during the deposition of polystyrene colloidal
      particles. We study the effects of the initial concentration of the suspension
      and compare the measured speeds with the corresponding dried deposit. It is
      observed that multilayer structures are associated with high speeds. This result
      is explained through a region in the bulk of the suspension where the
      concentration of particles increases until multilayer is formed depending on the
      porosity of the previously deposited structures.

PMID- 19391997
TI  - Density scaling of the diffusion coefficient at various pressures in viscous
      liquids.
AB  - Fundamental thermodynamics and an earlier elastic solid-state point defect model
      [P. Varotsos and K. Alexopoulos, Phys. Rev. B 15, 4111 (1977); Phys. Rev. B 18,
      2683 (1978)] are employed to formulate an analytical second-order polynomial
      function describing the density scaling of the diffusion coefficient in viscous
      liquids. The function parameters are merely determined by the scaling exponent,
      which is directly connected with the Gruneisen constant. Density scaling
      diffusion coefficient isotherms obtained at different pressures collapse on a
      unique master curve, in agreement with recent computer simulation results of
      Lennard-Jones viscous liquids [D. Coslovich and C. M. Roland, J. Phys. Chem. 112,
      1329 (2008)].

PMID- 19391998
TI  - Preferred orientation of n -hexane crystallized in silicon nanochannels: A
      combined x-ray diffraction and sorption isotherm study.
AB  - We present an x-ray diffraction study on n -hexane in tubular silicon channels of
      approximately 10 nm diameter both as a function of the filling fraction f of the
      channels and as a function of temperature. Upon cooling, confined n -hexane
      crystallizes in a triclinic phase typical of the bulk crystalline state. However,
      the anisotropic spatial confinement leads to a preferred orientation of the
      confined crystallites, where the 001 crystallographic direction coincides with
      the long axis of the channels. The magnitude of this preferred orientation
      increases with the filling fraction, which corroborates the assumption of a
      Bridgman-type crystallization process being responsible for the peculiar
      crystalline texture. This growth process predicts for a channel-like confinement
      an alignment of the fastest crystallization direction parallel to the long
      channel axis. It is expected to be increasingly effective with the length of
      solidifying liquid parcels and thus with increasing f . In fact, the fastest
      solidification front is expected to sweep over the full silicon nanochannel for
      f=1 , in agreement with our observation of a practically perfect texture for
      entirely filled nanochannels.

PMID- 19391999
TI  - Long-time dynamics of the directional solidification of rodlike eutectics.
AB  - We report long-duration real-time observations of the dynamics of hexagonal
      (rodlike) directional-solidification patterns in bulk samples of a transparent
      eutectic alloy. A slight forward curvature of the isotherms induces a slow
      dilatation of the growth pattern at constant solidification rate and triggers the
      rod-splitting instability. At long times, the rod-splitting frequency exactly
      balances the dilatation driven by the curved isotherms. The growth pattern is
      then disordered and nonstationary but has a sharply selected mean spacing. Well
      ordered growth patterns can be grown using time-dependent solidification rates.

PMID- 19392000
TI  - Reversible macroscopic dynamics of polar nematic liquid crystals: reversible
      currents and their experimental consequences.
AB  - Polar liquid crystalline phases are relevant for fluid liquid crystal phases
      observed in banana liquid crystals as well as for a class of polymeric liquid
      crystalline materials investigated recently. In this Brief Report we present the
      reversible dynamics for polar nematic liquid crystals with C_{infinityv}
      symmetry, where the macroscopic polarization representing polar order acts as an
      independent macroscopic variable. We find reversible coupling terms, for example,
      between flow and temperature and concentration gradients specific for the
      existence of a polar preferred direction. We suggest concrete experiments to
      check the importance of the reversible dynamic cross-coupling terms presented
      here.

PMID- 19392001
TI  - Predator-prey quasicycles from a path-integral formalism.
AB  - The existence of beyond mean-field quasicycle oscillations in a simple spatial
      model of predator-prey interactions is derived from a path-integral formalism.
      The results agree substantially with those obtained from analysis of similar
      models using system size expansions of the master equation. In all of these
      analyses, the discrete nature of predator-prey populations and finite-size
      effects lead to persistent oscillations in time, but spatial patterns fail to
      form. The path-integral formalism goes beyond mean-field theory and provides a
      focus on individual realizations of the stochastic time evolution of population
      not captured in the standard master-equation approach.

PMID- 19392002
TI  - Nanopore formation on unilamellar vesicles of long- and short-chain lipids.
AB  - The structure of unilamellar vesicles (ULVs), comprising long- and short-chain
      lipids, was investigated, and the formation of nanopores on the surface of the
      ULVs was confirmed under the condition of long- and short-chain lipids being
      separated. It was also revealed that the behavior of the structural phase
      transition from ULVs to bilayered micelles (bicelles) depends on the number of
      nanopores formed on the surface of the ULVs. Because both the rim structures of
      nanopores and bicelles are considered to be microdomains of short-chain lipids,
      this phase behavior was explained by considering the kinetic pathway of the
      growth of the rim domain. It was concluded that the phase segregation of lipids
      plays an essential role in the rim formation of nanopores as well as bicelles.

PMID- 19392003
TI  - Analytical results on Muller's ratchet effect in growing populations.
AB  - Fontanari introduced [Phys. Rev. Lett. 91, 218101 (2003)] a model for studying
      Muller's ratchet phenomenon in growing asexual populations. They studied two
      situations, either including a death probability for each newborn or not, but
      were able to find analytical (recursive) expressions only in the no-decay case.
      In this Brief Report a branching process formalism is used to find recurrence
      equations that generalize the analytical results of the original paper besides
      confirming the interesting effects their simulations revealed.

PMID- 19392004
TI  - Spiral formation and degeneration in heterogeneous excitable media.
AB  - Spontaneous spiral formation occurs when an excitation wave is input to a
      heterogeneous network of low- and high-light-intensity cells projected onto a
      light-sensitive Belousov-Zhabotinsky reaction. The range of network conditions
      where spirals form is increased if two waves are input at critical time
      intervals. Spirals degenerate to form multiple spirals and spirals trapped within
      excitable cells. Spiral formation and degeneration is dependent on network
      excitability, cell size, and network size. Results exhibit parallels with spiral
      formation in excitable biological systems such as the heart.

PMID- 19392005
TI  - Level statistics of words: finding keywords in literary texts and symbolic
      sequences.
AB  - Using a generalization of the level statistics analysis of quantum disordered
      systems, we present an approach able to extract automatically keywords in
      literary texts. Our approach takes into account not only the frequencies of the
      words present in the text but also their spatial distribution along the text, and
      is based on the fact that relevant words are significantly clustered (i.e., they
      self-attract each other), while irrelevant words are distributed randomly in the
      text. Since a reference corpus is not needed, our approach is especially suitable
      for single documents for which no a priori information is available. In addition,
      we show that our method works also in generic symbolic sequences (continuous
      texts without spaces), thus suggesting its general applicability.

PMID- 19392006
TI  - Failure in distinguishing colored noise from chaos using the "noise titration"
      technique.
AB  - Identifying chaos in experimental data-noisy data-remains a challenging problem
      for which conclusive arguments are still very difficult to provide. In order to
      avoid problems usually encountered with techniques based on geometrical
      invariants (dimensions, Lyapunov exponent, etc.), Poon and Barahona introduced a
      numerical titration procedure which compares one-step-ahead predictions of linear
      and nonlinear models [Proc. Natl. Acad. Sci. U.S.A. 98, 7107 (2001)]. We
      investigate the aformentioned technique in the context of colored noise or other
      types of nonchaotic behaviors. The main conclusion is that in several examples
      noise titration fails to distinguish such nonchaotic signals from low-dimensional
      deterministic chaos.

PMID- 19392007
TI  - Contribution of Reynolds stress distribution to the skin friction in compressible
      turbulent channel flows.
AB  - An exact relationship for the local skin friction is derived for the compressible
      turbulent wall-bounded flow (channel, pipe, flat plate). This expression is an
      extension of the compressible case of that derived by Fukagata [Phys. Fluids 14,
      L73 (2002)] in the case of incompressible wall-bounded flows. This decomposition
      shows that the skin friction can be interpreted as the contribution of four
      physical processes, i.e., laminar, turbulent, compressible, and a fourth coming
      from the interaction between turbulence and compressibility. Compressible
      numerical simulations show that, even at Mach number M=2 , the main contribution
      comes from the turbulence, i.e., the Reynolds stress term.

PMID- 19392008
TI  - Formation of regular structures in the process of phase separation.
AB  - Phase separation under directional quenching has been studied in a Cahn-Hilliard
      model. In distinct contrast to the disordered patterns which develop under a
      homogeneous quench, periodic stripe patterns are generated behind the quench
      front. Their wavelength is uniquely defined by the velocity of the quench
      interface in a wide range. Numerical simulations match perfectly analytical
      results obtained in the limit of small and large velocities of the quench
      interface. Additional periodic modulation of the quench interface may lead to
      cellular patterns. The quenching protocols analyzed are expected to be an
      effective tool in technological applications to design nanostructured materials.

PMID- 19392009
TI  - Detonation wave driven by condensation of supersaturated carbon vapor.
AB  - An experimental observation of a detonation wave driven by the energy of
      condensation of supersaturated carbon vapor is reported. The carbon vapor was
      formed by the thermal decay of unstable carbon suboxide C3O2 behind shock waves
      in mixtures containing 10-30% C3O2 in Ar. In the mixture 10% C3O2+Ar the
      insufficient heat release resulted in a regime of overdriven detonation. In the
      mixture 20% C3O2+Ar measured values of the pressure and wave velocity coincident
      with calculated Chapman-Jouguet parameters were attained. In the richest mixture
      30% C3O2+Ar an excess heat release caused the slowing down of the condensation
      rate and the regime of underdriven detonation was observed.

PMID- 19392010
TI  - Anisotropic magnetohydrodynamic spectral transfer in the diffusion approximation.
AB  - A theoretical model of spectral transfer for anisotropic magnetohydrodynamic
      (MHD) turbulence is introduced, approximating energy transport in wave vector (k)
      space as a nonlinear diffusion process, extending previous isotropic k -space
      diffusion theories for hydrodynamics and MHD. This formal closure at the spectral
      equation level may be useful in space and astrophysical applications.

PMID- 19392011
TI  - Molecular dynamics on diffusive time scales from the phase-field-crystal
      equation.
AB  - We extend the phase-field-crystal model to accommodate exact atomic
      configurations and vacancies by requiring the order parameter to be non-negative.
      The resulting theory dictates the number of atoms and describes the motion of
      each of them. By solving the dynamical equation of the model, which is a partial
      differential equation, we are essentially performing molecular dynamics
      simulations on diffusive time scales. To illustrate this approach, we calculate
      the two-point correlation function of a fluid.

PMID- 19392012
TI  - Partner switching stabilizes cooperation in coevolutionary prisoner's dilemma.
AB  - Previous studies suggest that cooperation prevails when individuals can switch
      their interaction partners quickly. However, it is still unclear how quickly
      individuals should switch adverse partners to maximize cooperation. To address
      this issue, we propose a simple model of coevolutionary prisoner's dilemma in
      which individuals are allowed to either adjust their strategies or switch their
      defective partners. Interestingly, we find that, depending on the game parameter,
      there is an optimal tendency of switching adverse partnerships that maximizes the
      fraction of cooperators in the population. We confirm that the stabilization of
      cooperation by partner switching remains effective under some situations, where
      either normalized or accumulated payoff is used in strategy updating, and where
      either only cooperators or all individuals are privileged to sever
      disadvantageous partners. We also provide an extended pair approximation to study
      the coevolutionary dynamics. Our results may be helpful in understanding the role
      of partner switching in the stabilization of cooperation in the real world.

PMID- 19392013
TI  - Scaling of clusters and winding-angle statistics of isoheight lines in two
      dimensional Kardar-Parisi-Zhang surfaces.
AB  - We investigate the statistics of isoheight lines of (2+1) -dimensional Kardar
      Parisi-Zhang model at different level sets around the mean height in the
      saturation regime. We find that the exponent describing the distribution of the
      height-cluster size behaves differently for level cuts above and below the mean
      height, while the fractal dimensions of the height-clusters and their perimeters
      remain unchanged. The statistics of the winding angle confirms the previous
      observation that these contour lines are in the same universality class as self
      avoiding random walks.

PMID- 19392014
TI  - Cooperation in aspiration-based N -person prisoner's dilemmas.
AB  - We propose a mathematical model of the N -person prisoner's dilemma game played
      by a continuous population of agents with a time-dependent aspiration level. The
      model-a system of differential equations-takes into account the evolution of the
      aspiration level and of the mean frequency of the cooperators in the population.
      The dependence of the asymptotic level of cooperation on the individual payoffs
      and on the transition rates determining the agent's reaction to the received
      payoffs is studied. In general the existence and the magnitude of the asymptotic
      level of cooperation depends on N , the payoffs and the transition rates, and
      decreases with increasing N .

PMID- 19392015
TI  - Dilemma game structure observed in traffic flow at a 2-to-1 lane junction.
AB  - Using a cellular automaton traffic model based on the stochastic optimal velocity
      model with appropriate assumptions for both incoming and outgoing vehicle
      boundaries, the so-called bottleneck issue on a lane-closing section was
      investigated in terms of game theory. In the system, two classified driver agents
      coexist: C agents (cooperative strategy) always driving in the first lane and D
      agents (defective strategy) trying to drive in a lower-density lane whether the
      first or the second lane. In high-density flow, D agents' interruption into the
      first lane from the second just before the lane-closing section creates a heavier
      traffic jam, which reduces social efficiency. This particular event can be
      described with a prisoner's dilemma game structure.

PMID- 19392016
TI  - Ising model on the Apollonian network with node-dependent interactions.
AB  - This work considers an Ising model on the Apollonian network, where the exchange
      constant J(i,j) approximately 1/(k(i)k(j))(mu) between two neighboring spins
      (i,j) is a function of the degree k of both spins. Using the exact geometrical
      construction rule for the network, the thermodynamical and magnetic properties
      are evaluated by iterating a system of discrete maps that allows for very precise
      results in the thermodynamic limit. The results can be compared to the
      predictions of a general framework for spin models on scale-free networks, where
      the node distribution P(k) approximately k(-gamma) , with node-dependent
      interacting constants. We observe that, by increasing mu , the critical behavior
      of the model changes from a phase transition at T=infinity for a uniform system
      (mu=0) to a T=0 phase transition when mu=1 : in the thermodynamic limit, the
      system shows no true critical behavior at a finite temperature for the whole mu >
      or = 0 interval. The magnetization and magnetic susceptibility are found to
      present noncritical scaling properties.

PMID- 19392017
TI  - Priority queues with bursty arrivals of incoming tasks.
AB  - Recently increased accessibility of large-scale digital records enables one to
      monitor human activities such as the interevent time distributions between two
      consecutive visits to a web portal by a single user, two consecutive emails sent
      out by a user, two consecutive library loans made by a single individual, etc.
      Interestingly, those distributions exhibit a universal behavior, D(tau)
      approximately tau(-delta) , where tau is the interevent time, and delta
      approximately 1 or 32 . The universal behaviors have been modeled via the waiting
      time distribution of a task in the queue operating based on priority; the waiting
      time follows a power-law distribution P(w)(tau) approximately tau(-alpha) with
      either alpha=1 or 32 depending on the detail of queuing dynamics. In these
      models, the number of incoming tasks in a unit time interval has been assumed to
      follow a Poisson-type distribution. For an email system, however, the number of
      emails delivered to a mail box in a unit time we measured follows a power-law
      distribution with general exponent gamma . For this case, we obtain analytically
      the exponent alpha , which is not necessarily 1 or 32 and takes nonuniversal
      values depending on gamma . We develop the generating function formalism to
      obtain the exponent alpha , which is distinct from the continuous time
      approximation used in the previous studies.

PMID- 19392018
TI  - Stabilization of multiarmed spiral waves by circularly polarized electric fields.
AB  - The influence of circularly polarized electric fields (CPEFs) on the stability of
      multiarmed spiral waves is investigated. It is shown that CPEFs can change the
      period of the multiarmed spirals. The average period is an important quantity of
      multiarmed spiral and it must be larger than a threshold for stable multiarmed
      spiral. After a counter-rotating CPEF with suitable amplitude and period is
      applied, the average period of the multiarmed spiral may increase, which
      stabilizes the multiarmed spiral.

PMID- 19392019
TI  - Noise in random Boolean networks.
AB  - We investigate the effect of noise on random Boolean networks. Noise is
      implemented as a probability p that a node does not obey its deterministic update
      rule. We define two order parameters, the long-time average of the Hamming
      distance between a network with and without noise, and the average frozenness,
      which is a measure of the extent to which a node prefers one of the two Boolean
      states. We evaluate both order parameters as function of the noise strength, and
      of the number of inputs per node K finding a smooth transition from deterministic
      (p=0) to fully stochastic (p=12) dynamics for networks with K < or = 2 , and a
      first-order transition at p=0 for K>2 . Most of the results obtained by computer
      simulation are also derived analytically. The average Hamming distance can be
      evaluated using the annealed approximation. In order to obtain the distribution
      of frozenness as function of the noise strength, more sophisticated self
      consistent calculations had to be performed. This distribution is a collection of
      delta peaks for K=1 , and it has a fractal sructure for K>1 , approaching a
      continuous distribution in the limit K1 .

PMID- 19392020
TI  - Pseudononstationarity in the scaling exponents of finite-interval time series.
AB  - The accurate estimation of scaling exponents is central in the observational
      study of scale-invariant phenomena. Natural systems unavoidably provide
      observations over restricted intervals; consequently, a stationary stochastic
      process (time series) can yield anomalous time variation in the scaling
      exponents, suggestive of nonstationarity. The variance in the estimates of
      scaling exponents computed from an interval of N observations is known for finite
      variance processes to vary as approximately 1N as N-->infinity for certain
      statistical estimators; however, the convergence to this behavior will depend on
      the details of the process, and may be slow. We study the variation in the
      scaling of second-order moments of the time-series increments with N for a
      variety of synthetic and "real world" time series, and we find that in particular
      for heavy tailed processes, for realizable N , one is far from this approximately
      1N limiting behavior. We propose a semiempirical estimate for the minimum N
      needed to make a meaningful estimate of the scaling exponents for model
      stochastic processes and compare these with some "real world" time series.

PMID- 19392021
TI  - Langevin approach for the dynamics of the contact process on annealed scale-free
      networks.
AB  - We study the dynamics of the contact process, one of the simplest nonequilibrium
      stochastic processes, taking place on a scale-free network. We consider the
      network topology as annealed, i.e., all links are rewired at each microscopic
      time step, so that no dynamical correlation can build up. This is a practical
      implementation of the absence of correlations assumed by mean-field approaches.
      We present a detailed analysis of the contact process in terms of a Langevin
      equation, including explicitly the effects of stochastic fluctuations in the
      number of particles in finite networks. This allows us to determine analytically
      the survival time for spreading experiments and the density of active sites in
      surviving runs. The fluctuations in the topological structure induce anomalous
      scaling effects with respect to the system size when the degree distribution has
      a hard upper bound. When the upper bound is soft, the presence of outliers with
      huge connectivity perturbs the picture even more, inducing an apparent shift of
      the critical point. In light of these findings, recent theoretical and numerical
      results in the literature are critically reviewed.

PMID- 19392022
TI  - Simple probabilistic algorithm for detecting community structure.
AB  - With the growing number of available social and biological networks, the problem
      of detecting the network community structure is becoming more and more important
      which acts as the first step to analyze these data. The community structure is
      generally regarded as that nodes in the same community tend to have more edges
      and less if they are in different communities. We propose a simple probabilistic
      algorithm for detecting community structure which employs expectation
      maximization (SPAEM). We also give a criterion based on the minimum description
      length to identify the optimal number of communities. SPAEM can detect
      overlapping nodes and handle weighted networks. It turns out to be powerful and
      effective by testing simulation data and some widely known data sets.

PMID- 19392023
TI  - Enhanced stochastic oscillations in autocatalytic reactions.
AB  - We study a simplified scheme of k coupled autocatalytic reactions, previously
      introduced by Togashi and Kaneko. The role of stochastic fluctuations is
      elucidated through the use of the van Kampen system-size expansion and the
      results compared with direct stochastic simulations. Regular temporal
      oscillations are predicted to occur for the concentration of the various chemical
      constituents, with an enhanced amplitude resulting from a resonance which is
      induced by the intrinsic graininess of the system. The associated power spectra
      are determined and have a different form depending on the number of chemical
      constituents k . We make detailed comparisons in the two cases k=4 and k=8 .
      Agreement between the theoretical and numerical results for the power spectrum is
      good in both cases. The resulting spectrum is especially interesting in the k=8
      system, since it has two peaks, which the system-size expansion is still able to
      reproduce accurately.

PMID- 19392024
TI  - Heterogeneous bond percolation on multitype networks with an application to
      epidemic dynamics.
AB  - Considerable attention has been paid, in recent years, to the use of networks in
      modeling complex real-world systems. Among the many dynamical processes involving
      networks, propagation processes-in which the final state can be obtained by
      studying the underlying network percolation properties-have raised formidable
      interest. In this paper, we present a bond percolation model of multitype
      networks with an arbitrary joint degree distribution that allows heterogeneity in
      the edge occupation probability. As previously demonstrated, the multitype
      approach allows many nontrivial mixing patterns such as assortativity and
      clustering between nodes. We derive a number of useful statistical properties of
      multitype networks as well as a general phase transition criterion. We also
      demonstrate that a number of previous models based on probability generating
      functions are special cases of the proposed formalism. We further show that the
      multitype approach, by naturally allowing heterogeneity in the bond occupation
      probability, overcomes some of the correlation issues encountered by previous
      models. We illustrate this point in the context of contact network epidemiology.

PMID- 19392025
TI  - Entropy of network ensembles.
AB  - In this paper we generalize the concept of random networks to describe network
      ensembles with nontrivial features by a statistical mechanics approach. This
      framework is able to describe undirected and directed network ensembles as well
      as weighted network ensembles. These networks might have nontrivial community
      structure or, in the case of networks embedded in a given space, they might have
      a link probability with a nontrivial dependence on the distance between the
      nodes. These ensembles are characterized by their entropy, which evaluates the
      cardinality of networks in the ensemble. In particular, in this paper we define
      and evaluate the structural entropy, i.e., the entropy of the ensembles of
      undirected uncorrelated simple networks with given degree sequence. We stress the
      apparent paradox that scale-free degree distributions are characterized by having
      small structural entropy while they are so widely encountered in natural, social,
      and technological complex systems. We propose a solution to the paradox by
      proving that scale-free degree distributions are the most likely degree
      distribution with the corresponding value of the structural entropy. Finally, the
      general framework we present in this paper is able to describe microcanonical
      ensembles of networks as well as canonical or hidden-variable network ensembles
      with significant implications for the formulation of network-constructing
      algorithms.

PMID- 19392026
TI  - World-trade web: topological properties, dynamics, and evolution.
AB  - This paper studies the statistical properties of the web of import-export
      relationships among world countries using a weighted-network approach. We analyze
      how the distributions of the most important network statistics measuring
      connectivity, assortativity, clustering, and centrality have coevolved over time.
      We show that all node-statistic distributions and their correlation structure
      have remained surprisingly stable in the last 20 years -and are likely to do so
      in the future. Conversely, the distribution of (positive) link weights is slowly
      moving from a log-normal density towards a power law. We also characterize the
      autoregressive properties of network-statistics dynamics. We find that network
      statistics growth rates are well-proxied by fat-tailed densities like the Laplace
      or the asymmetric exponential power. Finally, we find that all our results are
      reasonably robust to a few alternative, economically meaningful, weighting
      schemes.

PMID- 19392027
TI  - Dynamic computation of network statistics via updating schema.
AB  - Given a large network, computing statistics such as clustering coefficient, or
      modularity, is costly for large networks. When one more edge or vertex is added,
      traditional methods require that the full (expensive) computation be redone on
      this slightly modified graph. Alternatively, we introduce here a new approach:
      under modification to the graph, we update the statistics instead of computing
      them from scratch. In this paper we provide update schemes for a number of
      popular statistics, to include degree distribution, clustering coefficient,
      assortativity, and modularity. Our primary aim is to reduce the computational
      complexity needed to track the evolving behavior of large networks. As an
      important consequence, this approach provides efficient methods which may support
      modeling the evolution of dynamic networks to identify and understand critical
      transitions. Using the updating scheme, the network statistics can be computed
      much faster than re-calculating each time that the network evolves. We also note
      that the update formula can be used to determine which edge or node will lead to
      the extremal change of network statistics, providing a way of predicting or
      designing network evolution rules that would optimize some chosen statistic. We
      present our evolution methods in terms of a network statistics differential
      notation.

PMID- 19392028
TI  - Cylindrical phase separation in colloidal suspensions.
AB  - When left overnight undisturbed in a covered beaker, suspensions of polystyrene
      microspheres were found to undergo a distinctive kind of macroscopically visible
      phase separation. Microspheres migrated radially, leaving a vertically oriented
      cylinder near the center of the beaker that was devoid of microspheres. Cylinder
      formation was preceded by formation of a microsphere-free plate at the suspension
      surface, which may be the precursor of the cylinder. The cylindrical phase
      separation was found to depend on illumination, which suggests that low-level
      photon energy from the laboratory environment is sufficient to drive this
      surprising pattern formation. So long as suspension parameters were set within
      certain ranges, the cylindrical pattern occurred regularly.

PMID- 19392029
TI  - Statistical properties of spectral fluctuations for a quantum system with
      infinitely many components.
AB  - Extending the idea formulated in Makino [Phys. Rev. E 67, 066205 (2003)], that is
      based on the Berry-Robnik approach [M. V. Berry and M. Robnik, J. Phys. A 17,
      2413 (1984)], we investigate the statistical properties of a two-point spectral
      correlation for a classically integrable quantum system. The eigenenergy sequence
      of this system is regarded as a superposition of infinitely many independent
      components in the semiclassical limit. We derive the level number variance (LNV)
      in the limit of infinitely many components and discuss its deviations from
      Poisson statistics. The slope of the limiting LNV is found to be larger than that
      of Poisson statistics when the individual components have a certain accumulation.
      This property agrees with the result from the semiclassical periodic-orbit theory
      that is applied to a system with degenerate torus actions [D. Biswas, M. Azam,
      and S. V. Lawande, Phys. Rev. A 43, 5694 (1991)].

PMID- 19392030
TI  - Exponential localization of singular vectors in spatiotemporal chaos.
AB  - In a dynamical system the singular vector (SV) indicates which perturbation will
      exhibit maximal growth after a time interval tau . We show that in systems with
      spatiotemporal chaos the SV exponentially localizes in space. Under a suitable
      transformation, the SV can be described in terms of the Kardar-Parisi-Zhang
      equation with periodic noise. A scaling argument allows us to deduce a universal
      power law tau(-gamma) for the localization of the SV. Moreover the same exponent
      gamma characterizes the finite- tau deviation of the Lyapunov exponent in
      excellent agreement with simulations. Our results may help improve existing
      forecasting techniques.

PMID- 19392031
TI  - Origin of chaos near critical points of quantum flow.
AB  - The general theory of motion in the vicinity of a moving quantum nodal point
      (vortex) is studied in the framework of the de Broglie-Bohm trajectory method of
      quantum mechanics. Using an adiabatic approximation, we find that near any nodal
      point of an arbitrary wave function psi there is an unstable point (called the X
      point) in a frame of reference moving with the nodal point. The local phase
      portrait forms always a characteristic pattern called the "nodal-point- X -point
      complex." We find general formulas for this complex as well as necessary and
      sufficient conditions of validity of the adiabatic approximation. We demonstrate
      that chaos emerges from the consecutive scattering events of the orbits with
      nodal-point- X -point complexes. The scattering events are of two types (called
      type I and type II). A theoretical model is constructed yielding the local value
      of the Lyapunov characteristic numbers in scattering events of both types. The
      local Lyapunov characteristic number scales as an inverse power of the speed of
      the nodal point in the rest frame, implying that it scales proportionally to the
      size of the nodal-point- X -point complex. It is also an inverse power of the
      distance of a trajectory from the X point's stable manifold far from the complex.
      This distance plays the role of an effective "impact parameter." The results of
      detailed numerical experiments with different wave functions, possessing one,
      two, or three moving nodal points, are reported. Examples are given of regular
      and chaotic trajectories, and the statistics of the Lyapunov characteristic
      numbers of the orbits are found and compared to the number of encounter events of
      each orbit with the nodal-point- X -point complexes. The numerical results are in
      agreement with the theory, and various phenomena appearing at first as
      counterintuitive find a straightforward explanation.

PMID- 19392032
TI  - Prebifurcation noise amplification in a fiber laser.
AB  - We report on the experimental evidence of noise amplification in an erbium-doped
      fiber laser in the vicinity of saddle-node, period-doubling, and crisis
      bifurcations. We demonstrate this interesting phenomenon by analyzing the laser
      bifurcation diagrams and power spectra. Numerical simulations on the base of an
      advanced laser model display good agreement with the experimental results.

PMID- 19392033
TI  - Experimental synchronization of circuit oscillations induced by common telegraph
      noise.
AB  - Experimental realization and quantitative investigation of common-noise-induced
      synchronization of limit-cycle oscillations subject to random telegraph signals
      are performed using an electronic oscillator circuit. Based on our previous
      formulation [K. Nagai, Phys. Rev. E 71, 036217 (2005)], dynamics of the circuit
      is described as random-phase mappings between two limit cycles. Lyapunov
      exponents characterizing the degree of synchronization are estimated from
      experimentally determined phase maps and compared with linear damping rates of
      phase differences measured directly. Noisy on-off intermittency of the phase
      difference as predicted by the theory is also confirmed experimentally.

PMID- 19392034
TI  - Anderson transition in a three-dimensional kicked rotor.
AB  - We investigate Anderson localization in a three-dimensional (3D) kicked rotor. By
      a finite-size scaling analysis we identify a mobility edge for a certain value of
      the kicking strength k = k(c) . For k > k(c) dynamical localization does not
      occur, all eigenstates are delocalized and the spectral correlations are well
      described by Wigner-Dyson statistics. This can be understood by mapping the
      kicked rotor problem onto a 3D Anderson model (AM) where a band of metallic
      states exists for sufficiently weak disorder. Around the critical region k
      approximately k(c) we carry out a detailed study of the level statistics and
      quantum diffusion. In agreement with the predictions of the one parameter scaling
      theory (OPT) and with previous numerical simulations, the number variance is
      linear, level repulsion is still observed, and quantum diffusion is anomalous
      with <p(2)> proportional t(2/3) . We note that in the 3D kicked rotor the
      dynamics is not random but deterministic. In order to estimate the differences
      between these two situations we have studied a 3D kicked rotor in which the
      kinetic term of the associated evolution matrix is random. A detailed numerical
      comparison shows that the differences between the two cases are relatively small.
      However in the deterministic case only a small set of irrational periods was
      used. A qualitative analysis of a much larger set suggests that deviations
      between the random and the deterministic kicked rotor can be important for
      certain choices of periods. Heuristically it is expected that localization
      effects will be weaker in a nonrandom potential since destructive interference
      will be less effective to arrest quantum diffusion. However we have found that
      certain choices of irrational periods enhance Anderson localization effects.

PMID- 19392035
TI  - Motor-mediated alignment of microtubules in semidilute mixtures.
AB  - We propose and study a model of molecular motor-induced ordering in a
      cytoskeletal filament solution for the semidilute case. Motors attach to a pair
      of filaments and walk along the pair bringing them into closer alignment. In the
      semidilute regime multiple motors can bind a filament to several others and, for
      a critical motor density, induce a transition to an ordered phase with a nonzero
      mean orientation. The motors, on the one hand, cause closer filament alignment,
      and, on the other hand, induce fluctuations that are dependent on the relative
      orientation of the filaments to which the motors are attached. We develop a
      spatially homogenous, mean-field theory that explicitly accounts for a force
      dependent detachment rate of motors, which in turn affects the mean and the
      fluctuations of the net force acting on a filament. This model considers each
      filament to be in motor contact with all other filaments in the solution. We show
      that the transition to the oriented state changes from second order to first
      order when the force-dependent detachment becomes important.

PMID- 19392036
TI  - Small traveling clusters in attractive and repulsive Hamiltonian mean-field
      models.
AB  - Long-lasting small traveling clusters are studied in the Hamiltonian mean-field
      model by comparing between attractive and repulsive interactions. Nonlinear
      Landau damping theory predicts that a Gaussian momentum distribution on a
      spatially homogeneous background permits the existence of traveling clusters in
      the repulsive case, as in plasma systems, but not in the attractive case.
      Nevertheless, extending the analysis to a two-parameter family of momentum
      distributions of Fermi-Dirac type, we theoretically predict the existence of
      traveling clusters in the attractive case; these findings are confirmed by direct
      N -body numerical simulations. The parameter region with the traveling clusters
      is much reduced in the attractive case with respect to the repulsive case.

PMID- 19392037
TI  - Stochastic bifurcation in noise-driven lasers and Hopf oscillators.
AB  - This paper considers nonlinear dynamics in an ensemble of uncoupled lasers, each
      being a limit-cycle oscillator, which are driven by the same external white
      Gaussian noise. As the external-noise strength increases, there is an onset of
      synchronization and then subsequent loss of synchrony. Local analysis of the
      laser equations shows that synchronization becomes unstable via stochastic
      bifurcation to chaos, defined as a passing of the largest Lyapunov exponent
      through zero. The locus of this bifurcation is calculated in the three
      dimensional parameter space defined by the Hopf parameter, amount of amplitude
      phase coupling, and external-noise strength. Numerical comparison between the
      laser system and the normal form of Hopf bifurcation uncovers a square-root law
      for this stochastic bifurcation as well as strong enhancement in noise-induced
      chaos due to the laser's relaxation oscillation.

PMID- 19392038
TI  - Stability near threshold in a semiconductor laser subject to optical feedback: a
      bifurcation analysis of the Lang-Kobayashi equations.
AB  - Through the use of analytical and numerical techniques, we investigate the
      interaction between the trivial off-state and the continuous-wave (CW) operation
      of a semiconductor laser subject to conventional optical feedback. More
      specifically, using numerical continuation tools, the stability and bifurcations
      of the CW states, or external-cavity modes (ECMs), are analyzed in dependence on
      the parameters of feedback phase, feedback strength, pump current, and the
      linewidth enhancement factor. In this way, curves of codimension-one Hopf
      bifurcations are shown to destabilize the off-state and lead to stable ECM
      operation. Moreover, self-intersections of these Hopf curves in codimension-two
      Hopf-Hopf bifurcation points are seen to give rise to curves of codimension-one
      torus bifurcations (Hopf bifurcations of the ECMs), and degenerate-Hopf points to
      the birth of saddle-node bifurcations of the ECMs, as parameters are varied.
      These codimension-two points are shown to come together at a codimension-three
      degenerate Hopf-Hopf point (a Bogdanov-Takens bifurcation of the ECMs): a
      limiting point for which a stable off-state can exist.

PMID- 19392039
TI  - Tristability of a semiconductor laser due to time-delayed optical feedback.
AB  - We present an experimental and theoretical study of multistability of a single
      mode laser subject to feedback through phase tuning and amplifier sections
      integrated on the same chip. Closely above threshold, a regime of tristability of
      continuous-wave (CW) states is found for multiple ranges of amplifier and phase
      currents. The separation between the tristable wavelengths agrees with the
      channel spacing of dense wavelength multiplexing in the C band of optical
      communication making the device interesting for ternary logic applications.
      Complementary theoretical investigations in the framework of the paradigmatic
      Lang-Kobayashi model provide a consistent understanding of the experimental
      findings and additionally yield an analytic formula expressing the maximum number
      of coexisting stable CW states by the linewidth-enhancement factor alpha .
      Tristability belongs to the alpha range from 5 to 8 in good agreement with
      experiment.

PMID- 19392040
TI  - Drifting dynamics of dense and sparse spiral waves in heterogeneous excitable
      media.
AB  - Spiral wave is shown to drift in heterogeneous excitable media, yet the dynamics
      remains incompletely understood. In this study, we investigated the effects of
      heterogeneities in excitable media on the drifting behaviors of dense and sparse
      spiral waves. Dense spiral waves occur in media of normal excitability and sparse
      spiral waves in media of low excitability. We numerically simulated the spiral
      wave drifting in a reaction-diffusion system with the Barkley kinetics and showed
      that dense and sparse spiral waves drifted differently under the same
      heterogeneous medium. To understand the drifting behaviors, we developed a
      kinematic model to describe the tip properties of the spiral waves under
      different conditions and showed that the kinematic model could well recapitulate
      the results observed in the reaction-diffusion system.

PMID- 19392041
TI  - Quantum signatures of non-Newtonian orbits in the asymmetric infinite square
      well.
AB  - An infinite square well with a rectangular step is one of the simplest systems to
      exhibit non-Newtonian ray-splitting periodic orbits in the classical limit. We
      examine eigenvalue spacings in the quantum version of this system. The sequence
      of spacings shows deviations from uniformity at energies just above the step
      height and distinct resonance features are visible at certain energies.
      Semiclassical analysis shows that these features are directly related to the
      presence of non-Newtonian orbits in the classical system. In addition, the
      resonance features are shown to produce revivals in suitably constructed wave
      packets peaked at the resonance energy.

PMID- 19392042
TI  - Diffusion-induced instability and chaos in random oscillator networks.
AB  - We demonstrate that diffusively coupled limit-cycle oscillators on random
      networks can exhibit various complex dynamical patterns. Reducing the system to a
      network analog of the complex Ginzburg-Landau equation, we argue that uniform
      oscillations can be linearly unstable with respect to spontaneous phase
      modulations due to diffusional coupling-the effect corresponding to the Benjamin
      Feir instability in continuous media. Numerical investigations under this
      instability in random scale-free networks reveal a wealth of complex dynamical
      regimes, including partial amplitude death, clustering, and chaos. A dynamic mean
      field theory explaining different kinds of nonlinear dynamics is constructed.

PMID- 19392043
TI  - Stability analysis of a phase-field model of gravity-driven unsaturated flow
      through porous media.
AB  - The formation of preferential flow paths during infiltration of water into
      homogeneous, dry soil is an important phenomenon whose explanation and prediction
      have remained elusive under the standard theories of multiphase flow in porous
      media. We have recently proposed a macroscopic phase-field model of unsaturated
      flow in porous media, which explains why such fingering occurs [L. Cueto
      Felgueroso and R. Juanes, Phys. Rev. Lett. 101, 244504 (2008)]. Here we present a
      linear stability analysis of the proposed model for constant-flux infiltration,
      which allows a quantitative description of the wetting front instability. The
      present analysis stresses the critical role of the initial water saturation and
      applied flux ratio in the asymptotic stability of the system, as well as in the
      transient growth of perturbations, which is consistent with the experimental
      evidence. The trends in the frequency and growth factor of the most unstable
      modes predicted by our analysis are also in quantitative agreement with
      experimental measurements.

PMID- 19392044
TI  - Percolation and permeability of networks of heterogeneous fractures.
AB  - Networks composed by heterogeneous fractures whose local permeability is a binary
      correlated random field are generated. The percolation and permeability
      properties of a single heterogeneous fracture are strongly influenced by finite
      size effects when the correlation length is of the order of the fracture size.
      For fracture networks, a mean-field approximation is derived which approximates
      well the macroscopic permeability while an empirical formula is proposed for the
      percolation properties.

PMID- 19392045
TI  - Precessing rotating flows with additional shear: stability analysis.
AB  - We consider unbounded precessing rotating flows in which vertical or horizontal
      shear is induced by the interaction between the solid-body rotation (with angular
      velocity Omega(0)) and the additional "precessing" Coriolis force (with angular
      velocity -epsilonOmega(0)), normal to it. A "weak" shear flow, with rate 2epsilon
      of the same order of the Poincare "small" ratio epsilon , is needed for balancing
      the gyroscopic torque, so that the whole flow satisfies Euler's equations in the
      precessing frame (the so-called admissibility conditions). The base flow case
      with vertical shear (its cross-gradient direction is aligned with the main
      angular velocity) corresponds to Mahalov's [Phys. Fluids A 5, 891 (1993)]
      precessing infinite cylinder base flow (ignoring boundary conditions), while the
      base flow case with horizontal shear (its cross-gradient direction is normal to
      both main and precessing angular velocities) corresponds to the unbounded
      precessing rotating shear flow considered by Kerswell [Geophys. Astrophys. Fluid
      Dyn. 72, 107 (1993)]. We show that both these base flows satisfy the
      admissibility conditions and can support disturbances in terms of advected
      Fourier modes. Because the admissibility conditions cannot select one case with
      respect to the other, a more physical derivation is sought: Both flows are
      deduced from Poincare's [Bull. Astron. 27, 321 (1910)] basic state of a
      precessing spheroidal container, in the limit of small epsilon . A Rapid
      distortion theory (RDT) type of stability analysis is then performed for the
      previously mentioned disturbances, for both base flows. The stability analysis of
      the Kerswell base flow, using Floquet's theory, is recovered, and its counterpart
      for the Mahalov base flow is presented. Typical growth rates are found to be the
      same for both flows at very small epsilon , but significant differences are
      obtained regarding growth rates and widths of instability bands, if larger
      epsilon values, up to 0.2, are considered. Finally, both flow cases are briefly
      discussed in view of a subsequent nonlinear study using pseudospectral direct
      numerical simulations, which is a natural continuation of RDT.

PMID- 19392046
TI  - Optimizing transient transport in materials having two scales of porosity.
AB  - Porous materials having multiple scales of porosity afford the opportunity to
      combine the high surface area and functionality of nanopores with the superior
      charge/discharge characteristics of wider transport channels. However, the
      relative volume fractions assigned to nanopores and transport channels must be
      thoughtfully balanced because the introduction of transport channels reduces the
      volume available for nanopore functionality. In the present paper, the optimal
      balance between nanopore capacity and system response time is achieved by
      adjusting the aperture and spacing of a family of transport channels that provide
      access to adjacent nanopores during recharge/discharge cycles of materials
      intended for storage of gas or electric charge. A diffusive transport model is
      used to describe alternative processes of viscous gas flow, Knudsen gas flow, and
      ion diffusion or electromigration. The coupled transport equations for the
      nanopores and transport channels are linearized and solved analytically for a
      periodic variation in external gas pressure, ion concentration, or electric
      potential using a separation-of-variables approach in the complex domain.
      Optimization of these solutions yields closed-form expressions for channel
      apertures and spacing that provide maximum discharge of gas or electric charge
      for a fixed system volume and a desired discharge time.

PMID- 19392047
TI  - Stochastic transport of particles in straining flows.
AB  - Important features associated with the segregration of particles in turbulent
      flow are investigated by considering the statistical distribution (phase-space
      number density) of particles subject to the combined effects of straining flow
      and stochastic forcing. A Fokker-Planck model is used to obtain results for the
      phase-space distributions of particles that are entrained into straining flow
      fields. The analysis shows that, in marked contrast to the zero strain case,
      nonsingular steady-state distributions are generated, and also confirms that the
      diffusional effect resulting from stochastic forcing is sufficient to offset the
      otherwise singular distributions that would result from the indefinite
      accumulation of particles along stagnation lines. The influence of particle
      inertia (Stokes number) on the form of the resulting distributions is considered
      and several significant results are observed. The influence of strain rate on the
      attenuation of particle kinetic stresses is quantified and explained. The
      development of large third-order velocity moments is observed for Stokes numbers
      above a critical value. The mechanism underlying this phenomenon is seen to be a
      generic feature of particle transport in flows where vortex structures induce
      local counterflows of particles. The system therefore provides an ideal test for
      closure models for third-order moments of particle velocities, and here the
      standard Chapman-Enskog approximation is assessed.

PMID- 19392048
TI  - Drop impact onto a liquid layer of finite thickness: dynamics of the cavity
      evolution.
AB  - In the present work experimental, numerical, and theoretical investigations of a
      normal drop impact onto a liquid film of finite thickness are presented. The
      dynamics of drop impact on liquid surfaces, the shape of the cavity, the
      formation and propagation of a capillary wave in the crater, and the residual
      film thickness on the rigid wall are determined and analyzed. The shape of the
      crater within the film and the uprising liquid sheet formed upon the impact are
      observed using a high-speed video system. The effects of various influencing
      parameters such as drop impact velocity, liquid film thickness and physical
      properties of the liquids, including viscosity and surface tension, on the time
      evolution of the crater formation are investigated. Complementary to experiments
      the direct numerical simulations of the phenomena are performed using an advanced
      free-surface capturing model based on a two-fluid formulation of the classical
      volume-of-fluid (VOF) model in the framework of the finite volume numerical
      method. In this model an additional convective term is introduced into the
      transport equation for phase fraction, contributing decisively to a sharper
      interface resolution. Furthermore, an analytical model for the penetration depth
      of the crater is developed accounting for the liquid inertia, viscosity, gravity,
      and surface tension. The model agrees well with the experiments at the early
      times of penetration far from the wall if the impact velocity is high. Finally, a
      scaling analysis of the residual film thickness on the wall is conducted
      demonstrating a good agreement with the numerical predictions.

PMID- 19392049
TI  - Maximum size of drops levitated by an air cushion.
AB  - Liquid drops can be kept from touching a plane solid surface by a gas stream
      entering from underneath, as it is observed for water drops on a heated plate,
      kept aloft by a stream of water vapor. We investigate the limit of small flow
      rates, for which the size of the gap between the drop and the substrate becomes
      very small, to obtain a full analytical description of stationary drop states and
      their stability. Above a critical drop radius no stationary drops can exist,
      below the critical radius two solutions coexist. However, only the solution with
      the smaller gap width is stable, the other is unstable. We compare to
      experimental data and use boundary integral simulations to show that unstable
      drops develop a gas "chimney" that breaks the drop in its middle.

PMID- 19392050
TI  - Stability of the circular Couette flow of a ferrofluid in an axial magnetic
      field: influence of polydispersity.
AB  - The gap between two concentric rotating cylinders is filled with a ferrofluid. A
      homogeneous magnetic field is applied parallel to the cylinder axis. The
      stability of the circular Couette flow is analyzed with different models that
      take into account the polydispersity of the ferrofluid to a varying degree. Their
      results are compared and their merits are discussed.

PMID- 19392051
TI  - Families of subcritical spirals in highly counter-rotating Taylor-Couette flow.
AB  - A comprehensive numerical exploration of secondary finite-amplitude solutions in
      small-gap Taylor-Couette flow for high counter-rotating Reynolds numbers is
      provided, using Newton-Krylov methods embedded within arclength continuation
      schemes. Two different families of rotating waves have been identified: short
      axial wavelength subcritical spirals ascribed to centrifugal mechanisms and large
      axial scale supercritical spirals and ribbons associated with shear dynamics in
      the outer linearly stable radial region. This study is a first step taken in
      order to provide the inner structure of the skeleton of equilibria that may be
      responsible for the intermittent regime usually termed as spiral turbulence that
      has been reported by many experimentalists in the past.

PMID- 19392052
TI  - Flux-dependent percolation transition in immiscible two-phase flows in porous
      media.
AB  - Using numerical simulations, we study immiscible two-phase flow in a pore network
      reconstructed from Berea sandstone under flow conditions that are statistically
      invariant under translation. Under such conditions, the flow is a state function
      which is not dependent on initial conditions. We find a second-order phase
      transition resembling the phase inversion transition found in emulsions. The flow
      regimes under consideration are those of low surface tension-hence high capillary
      numbers Ca-where viscous forces dominate. Nevertheless, capillary forces are
      imminent, we observe a critical stage in saturation where the transition takes
      place. We determine polydispersity critical exponent tau=2.27+/-0.08 and find
      that the critical saturation depends on how fast the fluids flow.

PMID- 19392053
TI  - Mixing and segregation of microspheres in microchannel flows of mono- and
      bidispersed suspensions.
AB  - We investigate the mixing and segregation of mono- and bidispersed microsphere
      suspensions in microchannel flows. These flows are common in biological
      microelectromechanical systems (BioMEMS) applications handling blood or
      suspensions of DNA. Suspension transport in pressure driven flows is
      significantly hindered by shear-induced migration, where particles migrate away
      from the walls and are focused in the center due to multibody hydrodynamic
      interactions. The microchannels used in this study have geometries that induce
      chaotic advection in Newtonian fluids. Our results show that mixing in straight,
      herringbone and staggered herringbone channels depends strongly on volume
      fraction. Due to this complex interplay of advection and shear-induced migration,
      a staggered herringbone channel that typically results in chaotic mixing is not
      always effective for dispersing particles. The maximum degree of segregation is
      observed in a straight channel once the maximum packing fraction is reached at
      channel center. We modify a one-dimensional suspension balance model [R. Miller
      and J. Morris, J. Non-Newtonian Fluid Mech. 135, 149 (2006)] to describe the
      behavior at the center of the straight channel. The degree of mixing is then
      calculated as a function of bulk volume fraction, predicting the volume fraction
      that results in the maximum degree of segregation. In bidispersed suspension
      flow, it is shown that mixing of the larger species is enhanced in straight and
      staggered herringbone channels while segregation is enhanced at moderate volume
      fractions in herringbone channels. This suggests mixing and separations can be
      tailored by adjusting both the suspension properties and the channel geometry.

PMID- 19392054
TI  - Slip velocity and velocity inversion in a cylindrical Couette flow.
AB  - Velocity inversion in a nanoscale cylindrical Couette flow is investigated with
      the Navier-Stokes (NS) equation and molecular-dynamics (MD) simulation. With
      general slip boundary conditions in the NS equation, the flow can be classified
      into five distinct profiles. The condition of velocity inversion is explored in
      the whole space of four dimensionless variables of beta , slip velocity ratio
      u('), radius ratio a('), and angular velocity ratio omega('). MD computer
      simulations are performed to estimate the constitutive coefficient of the slip
      velocities at the walls. The flow is generated by a rotating inner wall and a
      stationary outer wall in conformity with the theoretical result. By varying an
      attraction parameter in the Lennard-Jones potential, the slip velocities can be
      easily controlled. The theoretical predictions are compared with the simulation
      results. We find that in the intermediate range of the attraction parameter the
      two results are quite comparable to some extent, but at both extreme values of
      the attraction parameter, they are quite different.

PMID- 19392055
TI  - Shear-induced self-diffusion of inertial particles in a viscous fluid.
AB  - We propose a theoretical prediction of the self-diffusion tensor of inertial
      particles embedded in a viscous fluid. The derivation of the model is based on
      the kinetic theory for granular media including the effects of finite particle
      inertia and drag. The self-diffusion coefficients are expressed in terms of the
      components of the kinetic stress tensor in a general formulation. The model is
      valid from dilute to dense suspensions and its accuracy is verified in a pure
      shear flow. The theoretical prediction is compared to simulations of discrete
      particle trajectories assuming Stokes drag and binary collisions. We show that
      the prediction of the self-diffusion tensor is accurate provided that the kinetic
      stress components are correctly predicted.

PMID- 19392056
TI  - Extraordinary increase of lifetime of localized cold clouds by the viscous effect
      in thermally unstable two-phase interstellar media.
AB  - We numerically examine the influence of the viscosity on the relaxation process
      of localized clouds in thermally unstable two-phase media, which are locally
      heated by cosmic ray and cooled by radiation. Pulselike stationary solutions of
      the media are numerically obtained by a shooting method. In one-dimensional
      direct numerical simulations, localized clouds are formed during the two-phase
      separation and sustained extraordinarily. Such long-lived clouds have been
      recently observed in interstellar media. We demonstrate that the balance of the
      viscosity with a pressure gradient remarkably suppresses the evaporation of the
      clouds and controls the relaxation process. This balance fixes the peak pressure
      of localized structures and then the structure is attracted and trapped to one of
      the pulselike stationary solutions. While the viscosity has been neglected in
      most of previous studies, our study suggests that the precise treatment of the
      viscosity is necessary to discuss the evaporation of the clouds.

PMID- 19392057
TI  - Onset of motion of a partly hidden cylinder in a laminar shear flow.
AB  - In this paper, the onset of motion of an isolated cylinder partially exposed to a
      shear flow is experimentally investigated. The experiments are performed in a
      small narrow channel which provides a vertical shear layer flow whose sizes
      correspond with the channel width. The bottom of the channel is smooth except in
      the test zone, at long distance from the inlet, where the cylinder is placed with
      its principal axis perpendicularly directed to the main flow. The geometry of the
      channel bottom at the test zone is such that the cylinder is partially buried and
      presents different expositions to the incident flow. In this way, the geometrical
      constraints imposed by the sediment bed on a single particle in a natural
      sediment transport situation are reproduced in an idealized context. The results
      are interpreted in terms of the relation between the particle mobility parameter
      at the critical condition and the here defined particle burial degree with
      respect to the bed geometrical constraints beta . We emphasize the role played by
      this burial degree that is dependent on the particle exposure to the incident
      flow E and the resistance to the motion by mechanical contacts with its
      surroundings given by the so-called static pivot angle varphi .

PMID- 19392058
TI  - Motion of plasma-dust structures and gas in a magnetic field.
AB  - Numerous studies have revealed that the superposition of magnetic field causes
      plasma-dust structures to rotate in the plane normal to the field. The only
      explanation for this rotation found in the literature is that the plasma-dust
      structures are acted upon by the forces of ion entrainment (ion drag forces) from
      ions moving under the effect of the magnetic field in the azimuthal direction.
      However, this study demonstrates that the experimentally observed motion of
      plasma-dust structures cannot be explained by the forces of ion entrainment
      alone. We show that the observed motion of plasma-dust structures is further
      affected by their entrainment by gas rotating under the effect of the moment of
      force IxB , which exists in regions of discharge with nonuniform magnetic field
      in the vicinity of solenoid end faces, as well as at the narrowing of cross
      section of the discharge channel. An eddy electric current exists in a discharge
      with strata in a uniform magnetic field; this current causes the rotation of gas
      and is associated with the noncollinearity of the gradients of plasma density and
      temperature. Estimates are provided for the density of this current and for its
      impact on the rotation of gas in a magnetic field. Recent experimental data by
      Karasev [Phys. Rev. E 74, 066403 (2003)] are discussed.

PMID- 19392059
TI  - Modes of three-dimensional dust crystals in dusty plasmas.
AB  - Three-dimensional finite systems of charged dust particles confined to concentric
      spherical shells in a dusty plasma, so-called "Yukawa balls," have been studied
      experimentally with respect to their dynamic properties. For that purpose, the
      three-dimensional thermal Brownian motion of the dust particles around their
      equilibrium positions was reconstructed with high accuracy. From that the dynamic
      properties in the form of mode patterns and frequencies are obtained from
      singular value decomposition and normal mode analysis. The dynamics of the Yukawa
      balls was found to be dominated by large-scale low-frequency shearlike modes.

PMID- 19392060
TI  - Electrical conductivity of carbon plasma.
AB  - The electrical conductivity of carbon plasmas is measured in the range of
      densities from about 0.6 solid density down to about 0.05 solid density, and
      reported for values of internal energy ranging from 2 to 22 kJ/gm . Plasmas are
      formed by rapid electrical discharge through thin graphite fibers immersed in a
      water bath. The pressure in the expanding plasma column is determined by use of a
      hydrodynamic model to describe the effect on the water surround. It is found that
      at constant internal energy per unit mass U, conductivity sigma varies with
      specific volume v as sigma = v(-alpha), where alpha is about 1 for U < 6 kJ gm ,
      and rises to about 1.5 for U = 22 kJ gm .

PMID- 19392061
TI  - Effect of trapped ions and nonequilibrium electron-energy distribution function
      on dust-particle charging in gas discharges.
AB  - Dust-particles charging in a low-pressure glow discharge was investigated
      theoretically. The dust-particle charge was found on the basis of a developed
      self-consistent model taking into account the nonequilibrium character of
      electron distribution function and the formation of an ionic coat composed of
      bound or trapped ions around the dust particle. The dust-particle charge, the
      radial distributions of electron density, free and trapped ions densities, and
      the distribution of electrostatic potential were found. It was shown that the non
      Maxwellian electron distribution function and collisional flux of trapped ions
      both reduce the dust-particle charge in comparison with that received with the
      help of the conventional orbital motion limited (OML) model. However, in rare
      collisional regimes in plasma when the collisional flux is negligible, the
      formation of ionic coat around a particle leads to a shielding of the proper
      charge of a dust particle. In low-pressure experiments, it is only possible to
      detect the effective charge of a dust particle that is equal to the difference
      between the proper charge of the particle and the charge of trapped ions. The
      calculated effective dust particle charge is in fairly good agreement with the
      experimental measurements of dust-particle charge dependence on gas pressure.

PMID- 19392062
TI  - Floquet-Liouville approach for calculating Stark profiles in plasmas in the
      presence of a strong oscillating field.
AB  - The formalism for the calculation of Stark line profiles in hot dense plasmas
      submitted to a strong oscillating field is extensively developed. The Liouville
      space, usually used to deal with the calculation of Stark profiles in dense
      plasmas, and the Floquet theory, developed to solve time-periodic problems, have
      been joined together to solve the time-dependent Liouville equation in the so
      called Floquet-Liouville formalism. The strong-oscillating-field spectroscopic
      signatures and their error estimations are discussed for hydrogen- and heliumlike
      aluminum lines.

PMID- 19392063
TI  - Time-dependent energetic proton acceleration and scaling laws in ultraintense
      laser-pulse interactions with thin foils.
AB  - A two-phase model, where the plasma expansion is an isothermal one when laser
      irradiates and a following adiabatic one after laser ends, has been proposed to
      predict the maximum energy of the proton beams induced in the ultraintense laser
      foil interactions. The hot-electron recirculation in the ultraintense laser-solid
      interactions has been accounted in and described by the time-dependent hot
      electron density continuously in this model. The dilution effect of electron
      density as electrons recirculate and spread laterally has been considered. With
      our model, the scaling laws of maximum ion energy have been achieved and the
      dependence of the scaling coefficients on laser intensity, pulse duration, and
      target thickness have been obtained. Some interesting results have been
      predicted: the adiabatic expansion is an important process of the ion
      acceleration and cannot be neglected; the whole acceleration time is about 10-20
      times of laser-pulse duration; the larger the laser intensity, the more sensitive
      the maximum ion energy to the change of focus radius, and so on.

PMID- 19392064
TI  - Solid-density plasma nanochannel generated by a fast single ion in condensed
      matter.
AB  - A plasma model of relaxation of a medium in heavy-ion tracks in condensed matter
      is proposed. The model is based on three assumptions: the Maxwell distribution of
      plasma electrons, localization of plasma inside the track nanochannel, and
      constant values of the plasma electron density and temperature during the x-ray
      irradiation. The model of multiple ionization of target atoms by a fast
      projectile ion is used to determine the initial conditions. An analysis of the
      results of the calculations performed makes it possible to define when the atomic
      relaxation model is a very rough approximation and the plasma relaxation model
      must be used. It is demonstrated that the plasma relaxation model adequately
      describes the x-ray spectra observed upon interaction of a fast ion with
      condensed target. The comparison with the experimental data justifies the
      reliability of the plasma relaxation model. Preassumptions of plasma relaxation
      model are validated by the molecular-dynamics simulation. An x-ray spectral
      method based on the plasma relaxation model is proposed for diagnostics of the
      plasma in fast ion tracks. The results obtained can be useful in examining the
      initial stage of defect formation in solids under irradiation with single fast
      heavy ions.

PMID- 19392065
TI  - Enhanced hot-electron localization and heating in high-contrast ultraintense
      laser irradiation of microcone targets.
AB  - We report experiments demonstrating enhanced coupling efficiencies of high
      contrast laser irradiation to nanofabricated conical targets. Peak temperatures
      near 200 eV are observed with modest laser energy (10 J), revealing similar hot
      electron localization and material heating to reduced mass targets (RMTs),
      despite having a significantly larger mass. Collisional particle-in-cell
      simulations attribute the enhancement to self-generated resistive (approximately
      10 MG) magnetic fields forming within the curvature of the cone wall, which
      confine energetic electrons to heat a reduced volume at the tip. This represents
      a different electron confinement mechanism (magnetic, as opposed to electrostatic
      sheath confinement in RMTs) controllable by target shape.

PMID- 19392066
TI  - Population of resonance and metastable atoms in a cylindrical volume of finite
      size.
AB  - A solution method of the Holstein-Biberman equation in the case of two
      dimensional finite-size geometry by means of transformation of the integral
      operator to a four-dimensional matrix is presented. Using this matrix the array
      of two-dimensional eigenvalues and eigenfunctions of the radiation transport
      operator in the case of finite cylinder is determined. The exact two-dimensional
      characteristics have been compared with approximate functions determined as a
      combination of corresponding eigenvalues and eigenfunctions for the one
      dimensional problems (cylinder of infinite length and slab). The spatiotemporal
      evolution of excited atom densities for two typical forms of the excitation
      source in a nonequilibrium plasma has been analyzed. The reasons for the distinct
      difference in the formation of spatiotemporal distributions of resonance and
      metastable atoms in the case when the spatial distribution of the excitation
      source does not coincide with the fundamental mode are discussed. Resonance atoms
      follow the excitation source while the diffusion effectively takes metastable
      atoms out from the excitation source. Rearrangement of metastable atoms to the
      fundamental mode during their decay lasts about one effective diffusion lifetime
      while the corresponding process for the resonance atoms takes much longer
      (several effective lifetimes). The differences are caused by the effective
      suppression of higher diffusion modes compared with radiation modes. The
      developed solution method treats the radiation transport processes at the same
      accuracy level as diffusion transport of other plasma components and it is
      suitable for a self-consistent modeling of nonequilibrium plasmas.

PMID- 19392067
TI  - Soliton ratchets in sine-Gordon systems with additive inhomogeneities.
AB  - We investigate the ratchet dynamics of solitons of a sine-Gordon system with
      additive inhomogeneities. We show by means of a collective coordinate approach
      that the soliton moves like a particle in an effective potential which is a
      result of the inhomogeneities. Different degrees of freedom of the soliton are
      used as collective coordinates in order to study their influence on the motion of
      the soliton. The collective coordinates considered are the soliton position, its
      width and offset, and the height of the spikes that appear on the soliton. The
      results of the theory are compared with numerical simulations of the full system.

PMID- 19392068
TI  - Generalized Debye series expansion of electromagnetic plane wave scattering by an
      infinite multilayered cylinder at oblique incidence.
AB  - The Debye series expansion expresses the Mie scattering coefficients into a
      series of Fresnel coefficients and gives physical interpretation of different
      scattering modes, but when an infinite multilayered cylinder is obliquely
      illuminated by electromagnetic plane waves, the scattering process becomes very
      complicated because of cross polarization. Based on the relation of boundary
      conditions between global scattering process and local scattering processes, the
      generalized Debye series expansion of plane wave scattering by an infinite
      multilayered cylinder at oblique incidence is derived in this paper. The formula
      and the code are verified by the comparison of the results with that of Lorenz
      Mie theory in special cases and those presented in the literatures.

PMID- 19392069
TI  - Dynamics of metastable breathers in nonlinear chains in acoustic vacuum.
AB  - The study of the dynamics of one-dimensional chains with both harmonic and
      nonlinear interactions, as in the Fermi-Pasta-Ulam and related problems, has
      played a central role in efforts to identify the broad consequences of
      nonlinearity in these systems. Nevertheless, little is known about the dynamical
      behavior of purely nonlinear chains where there is a complete absence of the
      harmonic term, and hence sound propagation is not admissible, i.e., under
      conditions of "acoustic vacuum." Here we study the dynamics of highly localized
      excitations, or breathers, which are known to be initiated by the quasistatic
      stretching of the bonds between adjacent particles. We show via detailed particle
      dynamics-based studies that many low-energy pulses also form in the vicinity of
      the perturbation, and the breathers that form are "fragile" in the sense that
      they can be easily delocalized by scattering events in the system. We show that
      the localized excitations eventually disperse, allowing the system to attain an
      equilibrium-like state that is realizable in acoustic vacuum. We conclude with a
      discussion of how the dynamics is affected by the presence of acoustic
      oscillations.

PMID- 19392070
TI  - Noise effects in the ac-driven Frenkel-Kontorova model.
AB  - The noise effects on dynamical-mode-locking phenomena in the ac-driven
      dissipative Frenkel-Kontorova model are studied by molecular-dynamics
      simulations. It was found that the noise strongly influences the properties of
      the Shapiro steps and the way they respond to the changing of system parameters.
      The increase of temperature produces the melting of the Shapiro steps, while the
      critical depinning force is significantly reduced. The oscillatory form of the
      amplitude dependence is strongly affected where the Bessel-like form changes as
      the temperature increases. In the frequency dependence of the Shapiro steps, due
      to the decrease of the dc threshold value, noise may transfer the system to the
      high-amplitude regime where oscillations of the step width with frequency or
      period of the ac force appear. These phenomena will additionally destabilize the
      steps in real systems and significantly limit the region of parameters where
      dynamical-mode-locking phenomena could be observed.

PMID- 19392071
TI  - Determination of the apsidal angles and Bertrand's theorem.
AB  - We derive an expression for the determination of the apsidal angles that holds
      good for arbitrary central potentials. This formula can be useful in the
      calculation of precession rates. Then we discuss under what conditions the
      apsidal angles remain independent of the mechanical energy and angular momentum
      in the central force problem and, as a consequence, an alternative and
      nonperturbative proof of Bertrand's theorem is obtained.

PMID- 19392072
TI  - Stochastic differential equation approach for waves in a random medium.
AB  - We present a mathematical approach that simplifies the theoretical treatment of
      electromagnetic localization in random media and leads to closed-form analytical
      solutions. Starting with the assumption that the dielectric permittivity of the
      medium has delta-correlated spatial fluctuations, and using Ito's lemma, we
      derive a linear stochastic differential equation for a one-dimensional random
      medium. The equation leads to localized wave solutions. The localized wave
      solutions have a localization length that scales as L approximately omega(-2) for
      low frequencies whereas in the high-frequency regime this length behaves as L
      approximately omega(-2/3) .

PMID- 19392073
TI  - Single-scattering optical tomography.
AB  - We consider the problem of optical tomographic imaging in the mesoscopic regime
      where the photon mean-free path is on the order of the system size. It is shown
      that a tomographic imaging technique can be devised which is based on the
      assumption of single scattering and utilizes a generalization of the Radon
      transform which we refer to as the broken-ray transform. The technique can be
      used to recover the extinction coefficient of an inhomogeneous medium from
      angularly resolved measurements and is illustrated with numerical simulations.
      The forward data for these simulations were obtained by numerically solving the
      radiative transport equation without any approximations. Tomographic imaging in
      slabs of different widths was considered and it was shown that the technique can
      tolerate a maximum width that corresponds to approximately six scattering events.
      It is also shown that the use of broken rays does not result in additional ill
      posedness of the inverse problem in comparison to the classical problem of
      inverting the Radon transform. Applications to biomedical imaging are described.

PMID- 19392074
TI  - Zero-width band gap associated with the n[over] = 0 condition in photonic
      crystals containing left-handed materials.
AB  - We demonstrate that the band structure of a photonic crystal consisting of
      alternating layers of right-handed material (RHM) and left-handed material (LHM)
      can exhibit two types of zero- n[over ] gaps of zero width. It is shown that each
      type has an associated null-gap condition which determines the scaling properties
      of the frequency nu(0) at which the corresponding null gap occurs. Specifically,
      while scaling in the layer thicknesses does not modify the value of the frequency
      nu(0) determined by one of these conditions, the frequency nu(0) associated with
      the other one does not exhibit such a scaling behavior. We have also shown that
      near the touching point nu(0) (for both types of null gaps) and around the center
      of the Brillouin zone, the dispersion curves exhibit a linear dependence on the
      Bloch wave vector k . As a consequence, the corresponding density of states and
      group velocity are practically flat as functions of k in the neighborhood of k=0
      . Another interesting property of the considered structure is that an
      electromagnetic wave with frequency nu(0) can be transmitted through a finite RHM
      LHM photonic crystal without any change in amplitude and phase.

PMID- 19392075
TI  - Recursive Schrodinger equation approach to faster converging path integrals.
AB  - By recursively solving the underlying Schrodinger equation, we set up an
      efficient systematic approach for deriving analytic expressions for discretized
      effective actions. With this, we obtain discrete short-time propagators for both
      one and many particles in arbitrary dimension to orders that have not been
      accessible before. They can be used to substantially speed up numerical Monte
      Carlo calculations of path integrals, as well as for setting up an alternative
      analytical approximation scheme for energy spectra, density of states, and other
      statistical properties of quantum systems.

PMID- 19392076
TI  - Diffuse-interface model for smoothed particle hydrodynamics.
AB  - Diffuse-interface theory provides a foundation for the modeling and simulation of
      microstructure evolution in a very wide range of materials, and for the tracking
      and capturing of dynamic interfaces between different materials on larger scales.
      Smoothed particle hydrodynamics (SPH) is also widely used to simulate fluids and
      solids that are subjected to large deformations and have complex dynamic
      boundaries and/or interfaces, but no explicit interface tracking or capturing is
      required, even when topological changes such as fragmentation and coalescence
      occur, because of its Lagrangian particle nature. Here we developed a SPH model
      for single-component two-phase fluids that is based on diffuse-interface theory.
      In the model, the interface has a finite thickness and a surface tension that
      depend on the coefficient k of the gradient contribution to the Helmholtz free
      energy functional and the density-dependent homogeneous free energy. In this
      model, there is no need to locate the surface (or interface) or to compute the
      curvature at and near the interface. One- and two-dimensional SPH simulations
      were used to validate the model.

PMID- 19392077
TI  - Generalized Maxwell state and H theorem for computing fluid flows using the
      lattice Boltzmann method.
AB  - Generalized Maxwell distribution function is derived analytically for the lattice
      Boltzmann (LB) method. All the previously introduced equilibria for LB are found
      as special cases of the generalized Maxwellian. The generalized Maxwellian is
      used to derive a different class of multiple relaxation-time LB models and prove
      the H theorem for them.

PMID- 19392078
TI  - Hierarchical coarse-graining transform.
AB  - We present a hierarchical transform that can be applied to Laplace-like
      differential equations such as Darcy's equation for single-phase flow in a porous
      medium. A finite-difference discretization scheme is used to set the equation in
      the form of an eigenvalue problem. Within the formalism suggested, the pressure
      field is decomposed into an average value and fluctuations of different kinds and
      at different scales. The application of the transform to the equation allows us
      to calculate the unknown pressure with a varying level of detail. A procedure is
      suggested to localize important features in the pressure field based only on the
      fine-scale permeability, and hence we develop a form of adaptive coarse graining.
      The formalism and method are described and demonstrated using two synthetic toy
      problems.

PMID- 19392079
TI  - Corrected momentum exchange method for lattice Boltzmann simulations of
      suspension flow.
AB  - Standard methods for lattice Boltzmann simulations of suspended particles, based
      on the momentum exchange algorithm, might lack accuracy or violate Galilean
      invariance in some particular situations. Aiming at simulations of dense
      suspensions in high-shear flows, we motivate and investigate necessary correction
      terms. We propose an approach which, combining accurate treatments of fluid
      structure interaction and moving boundaries, is able to preserve Galilean
      invariance in relevant orders and to improve the physical behavior of the system.
      We validate the approach in a comparison with standard methods in simple test
      problems.

PMID- 19392080
TI  - Lees-Edwards boundary conditions for lattice Boltzmann suspension simulations.
AB  - When sheared suspensions are simulated, Lees-Edwards boundary conditions allow
      more realistic computational setups as they remove the need of a domain bounded
      by shearing walls (as in Couette-type flow) which bias typical flow structures.
      Lees-Edwards boundary conditions therefore allow investigation of pure bulk
      properties in a quasi-infinite system. In addition, they improve the
      computational efficiency of the simulations as the whole domain can be used to
      calculate averages. We propose an implementation of Lees-Edwards boundary
      conditions for lattice Boltzmann simulations of particulate suspensions, combined
      with an accurate treatment of fluid-particle interactions. The algorithm is
      validated using a simple single-particle benchmark and further applied to a fully
      resolved suspension flow. Shear-thickening behavior, which is prolonged to higher
      shear rates as compared to Couette flow results, could be observed.

PMID- 19392081
TI  - Momentum-shell renormalization-group flow from simulation.
AB  - Our recently developed Fourier Monte Carlo algorithm permits a nonperturbative
      calculation of momentum-shell renormalization-group flows by simulation which
      despite its apparent simplicity is illustrative both numerically as well as
      conceptually interesting. We study the example of a varphi(4) model with long
      range lattice interaction. For this model we show that the topology of the
      renormalization flow is globally accessible in a particularly convenient way. The
      nontrivial fixed point of Wilson-Fisher type is observed its accompanying
      critical exponents are numerically determined from fitting its surrounding flow
      pattern to a linearized renormalization-group transformation. The results are
      compared to those obtained from perturbation theory, -expansion and earlier Monte
      Carlo simulations. Application of our method is also expected to be rewarding in
      other models with long-range interactions.

PMID- 19392082
TI  - Implicit restart Lanczos as an eigensolver.
AB  - This paper investigates the efficiency of the implicit restart Lanczos and simple
      (without reorthogonalization) Lanczos algorithms, as eigensolvers for large scale
      computations in molecular and chemical physics. Using the cardioid billiard and
      the hydrogen cyanide/hydrogen isocyanide (HCN/HNC) molecule as model systems we
      demonstrate superior efficiency of implicit restart Lanczos compared to the
      simple Lanczos algorithm. A modified implementation of implicit restart Lanczos
      is also presented which works with a smaller Krylov space-with associated savings
      in memory-and can handle larger basis sets than the usual implicit restart
      Lanczos. It also enables getting all eigenpairs of a matrix, or all eigenvalues
      below a threshold (where the number of such is not known before hand), which is
      more difficult with the usual implicit restart algorithm.

PMID- 19392083
TI  - Microscopic and macroscopic stress with gravitational and rotational forces.
AB  - Many recent papers have questioned Irving and Kirkwood's atomistic expression for
      stress. In Irving and Kirkwood's approach both interatomic forces and atomic
      velocities contribute to stress. It is the velocity-dependent part that has been
      disputed. To help clarify this situation we investigate (i) a fluid in a
      gravitational field and (ii) a steadily rotating solid. For both problems we
      choose conditions where the two stress contributions, potential and kinetic, are
      significant. The analytic force-balance solutions of both these problems agree
      very well with a smooth-particle interpretation of the atomistic Irving-Kirkwood
      stress tensor.

PMID- 19392084
TI  - Grid method for computation of generalized spheroidal wave functions based on
      discrete variable representation.
AB  - We present an efficient and accurate grid method for computations of eigenvalues
      and eigenfunctions of the generalized spheroidal wave equation. Different from
      previous studies, our method is based on the expansion of the spheroidal wave
      function by discrete-variable-representation basis functions constructed from the
      associated Legendre polynomials. The differential operator can be expressed
      analytically on the grid points, which are the zeros of the associated Legendre
      polynomials. The resultant potential matrix is simply diagonal and evaluated
      directly on the same grid. The corresponding differential equation is thus
      converted to an eigenvalue problem of a small matrix, whose eigenvalues and
      eigenvectors are converged very fast. The wave functions can then be evaluated
      accurately at any desired point from the expansion formula with the computed
      eigenvectors. Compared to previous methods, our method is direct and efficient
      for any parameter c , either small or large.

PMID- 19392085
TI  - Fluctuations in interbank network dynamics.
AB  - This work investigates the scaling properties of fluctuations in the flux of
      individual agents with respect to their average flux in an interbank network. The
      analyzed data provide information on daily values of f(i)(asset), the credit
      provided by bank i in the interbank network, and f(i)(liab), the credit received
      by bank i from the other banks of the network. The investigation focuses on the
      scaling properties of the fluctuations in the raw data f(i)(asset), f(i)(liab),
      and f(R,i)(ext)(t) = f(i)(asset)-f(i)(liab), as well as on similar properties
      internal and external fluctuations f(i)(int) and f(i)(ext), which are derived
      according to a recently proposed methodology [M. Argollo de Menezes and A. L.
      Barabasi, Phys. Rev. Lett. 93, 068701 (2004)]. Finally, a "rolling sampling"
      approach is introduced in order to deal with the nonstationarity of the fluxes.
      The results suggest that exponents are time varying, hinting that the considered
      interbank network is changing with time.

PMID- 19392086
TI  - Invisible grazings and dangerous bifurcations in impacting systems: the problem
      of narrow-band chaos.
AB  - We discovered a narrow band of chaos close to the grazing condition for a simple
      soft impact oscillator. The phenomenon was observed experimentally for a range of
      system parameters. Through numerical stability analysis, we argue that this
      abrupt onset to chaos is caused by a dangerous bifurcation in which two unstable
      period-3 orbits, created at "invisible" grazings, take part.

PMID- 19392087
TI  - Realization of electron degeneracy effects as virtual upshifting in the
      ionization energies in the classical Saha equation.
AB  - We explain that the effects of electron degeneracy on the calculation of
      ionization equilibrium can be implemented and simply realized as virtual
      upshifting in the ionization energies in the classical Saha equation. Previous
      quantitative findings indicating depressed quantum statistical ionization
      compared to classical ionization are derived and abstracted in an analytical
      form. A simple ready-to-use approximate formula for the upshifting in ionization
      energies due to partial degeneracy is presented and used to work a sample
      problem.

PMID- 19392088
TI  - Higher-order effects and ultrashort solitons in left-handed metamaterials.
AB  - Starting from Maxwell's equations, we use the reductive perturbation method to
      derive a second-order and a third-order nonlinear Schrodinger equation,
      describing ultrashort solitons in nonlinear left-handed metamaterials. We find
      necessary conditions and derive exact bright and dark soliton solutions of these
      equations for the electric and magnetic field envelopes.

PMID- 19392089
TI  - Convergence rate for numerical computation of the lattice Green's function.
AB  - Flexible boundary-condition methods couple an isolated defect to bulk through the
      bulk lattice Green's function. Direct computation of the lattice Green's function
      requires projecting out the singular subspace of uniform displacements and forces
      for the infinite lattice. We calculate the convergence rates for elastically
      isotropic and anisotropic cases for three different techniques: relative
      displacement, elastic Green's function correction, and discontinuity correction.
      The discontinuity correction has the most rapid convergence for the general case.

PMID- 19392090
TI  - Comment on "Observation of neutronless fusion reactions in picosecond laser
      plasmas".
AB  - The paper by Belyaev [Phys. Rev. E 72, 026406 (2005)] reported the first
      experimental observation of alpha particles produced in the thermonuclear
      reaction 11B(p,alpha)8Be induced by laser irradiation on a 11B polyethylene (CH2)
      composite target. The laser used in the experiment is characterized by a
      picosecond pulse duration and a peak of intensity of 2x10(18) W/cm(2). We suggest
      that both the background-reduction method adopted in their detection system and
      the choice of the detection energy region of the reaction products are possibly
      inadequate. Consequently the total yield reported underestimates the true yield.
      Based on their observation, we give an estimation of the total yield to be higher
      than their conclusion, i.e., of the order of 10(5)alpha per shot.

PMID- 19392091
TI  - Essay: computers in the APS editorial office: the early years.
AB  - APS journals in the late 1960s began to move from hot-metal print shops to tailor
      made typewriters, next to special keyboards and a small computer, then to
      completely photocomposed journal pages. At the same time, internal editorial
      operations were being converted from paper handling and data records to
      completely electronic procedures. By 1990, it became feasible for authors to
      submit manuscripts to the journal electronically.

PMID- 19392092
TI  - Entanglement, nonlinear dynamics, and the heisenberg limit.
AB  - We show that quantum Fisher information provides a sufficient condition to
      recognize multiparticle entanglement in an N qubit state. The same criterion
      gives a necessary and sufficient condition for sub-shot-noise phase sensitivity
      in the estimation of a collective rotation angle theta. The analysis therefore
      singles out the class of entangled states which are useful to overcome classical
      phase sensitivity in metrology and sensors. We finally study the creation of
      useful entangled states by the nonlinear dynamical evolution of two decoupled
      Bose-Einstein condensates or trapped ions.

PMID- 19392093
TI  - Vanishing quantum discord is necessary and sufficient for completely positive
      maps.
AB  - Two long-standing open problems in quantum theory are to characterize the class
      of initial system-bath states for which quantum dynamics is equivalent to (i) a
      map between the initial and final system states, and (ii) a completely positive
      (CP) map. The CP map problem is especially important, due to the widespread use
      of such maps in quantum information processing and open quantum systems theory.
      Here we settle both these questions by showing that the answer to the first is
      "all", with the resulting map being Hermitian, and that the answer to the second
      is that CP maps arise exclusively from the class of separable states with
      vanishing quantum discord.

PMID- 19392094
TI  - Coherent control of dressed matter waves.
AB  - We demonstrate experimentally that matter waves can be coherently and
      adiabatically loaded and controlled in one-, two-, and three-dimensional strongly
      driven optical lattices. This coherent control is then used in order to
      reversibly induce the superfluid-Mott insulator phase transition by changing the
      strength of the driving. Our findings pave the way for studies of driven quantum
      systems and new methods for controlling matter waves.

PMID- 19392095
TI  - Efficient quantum circuits for one-way quantum computing.
AB  - While Ising-type interactions are ideal for implementing controlled phase flip
      gates in one-way quantum computing, natural interactions between solid-state
      qubits are most often described by either the XY or the Heisenberg models. We
      show an efficient way of generating cluster states directly using either the
      imaginary SWAP (iSWAP) gate for the XY model, or the sqrt[SWAP] gate for the
      Heisenberg model. Our approach thus makes one-way quantum computing more feasible
      for solid-state devices.

PMID- 19392096
TI  - Quantum noise as an entanglement meter.
AB  - Transport in a quantum point contact (QPC) can be used to generate many-body
      entanglement of Fermi seas in the leads. A universal relation is found between
      the generated entanglement entropy and the fluctuations of electric current,
      which is valid for any protocol of driving the QPC. This relation offers a basis
      for direct electric measurement of entanglement entropy. In particular, by
      utilizing space-time duality of 1D systems, we relate electric noise generated by
      opening and closing the QPC periodically in time with the seminal S=1/3logL
      prediction of conformal field theory.

PMID- 19392097
TI  - Enhancing the detection of natural thermal entanglement with disorder.
AB  - Physical systems have some degree of disorder present in them. We discuss how to
      treat natural, thermal entanglement in any random macroscopic system from which a
      thermodynamic witness bounded by a constant can be found. We propose that
      functional many-body perturbation theory be applied to allow either a quenched or
      an annealed average over the disorder to be taken. We find, when considering the
      example of an XX Heisenberg spin chain with a random coupling strength, that the
      region of natural entanglement detected by both witnesses can be enhanced by the
      disorder.

PMID- 19392098
TI  - Odd- and even-order dispersion cancellation in quantum interferometry.
AB  - We describe a novel effect involving odd-order dispersion cancellation. We
      demonstrate that odd- and even-order dispersion cancellation may be obtained in
      different regions of a single quantum interferogram using frequency
      anticorrelated entangled photons and a new type of quantum interferometer. This
      offers new opportunities for quantum communication and metrology in dispersive
      media.

PMID- 19392099
TI  - Cross correlations in scaling analyses of phase transitions.
AB  - Thermal or finite-size scaling analyses of importance sampling Monte Carlo
      computer simulations in the vicinity of phase transition points often combine
      different estimates for the same quantity, such as a critical exponent, with the
      intent to reduce statistical fluctuations. We point out that the origin of such
      estimates in the same time series often results in pronounced cross correlations
      which are usually ignored even in high-precision studies, generically leading to
      significant underestimation of statistical fluctuations. We suggest to use a
      simple extension of the conventional analysis taking correlation effects into
      account, which leads to improved estimators with often substantially reduced
      statistical fluctuations at almost no extra cost in terms of computation time.

PMID- 19392100
TI  - Connection between a possible fifth force and the direct detection of dark
      matter.
AB  - If there were a fifth force in the dark sector and dark matter (DM) particles
      interacted nongravitationally with ordinary matter, quantum corrections
      generically would lead to a fifth force in the visible sector. We show how the
      strong experimental limits on fifth forces in the visible sector produce bounds
      on the cross section for DM detection and the strength of the fifth force in the
      dark sector. For a fifth force comparable in strength to gravity, the spin
      independent direct detection cross section must typically be less, similar10;{
      55} cm;{2}. The anomalous acceleration of ordinary matter falling towards dark
      matter would also be constrained: eta_{OM-DM} less, similar10;{-8}.

PMID- 19392101
TI  - Improved limit on the permanent electric dipole moment of 199Hg.
AB  - We report the results of a new experimental search for a permanent electric
      dipole moment of 199Hg utilizing a stack of four vapor cells. We find
      d(199Hg)=(0.49+/-1.29_{stat}+/-0.76_{syst})x10;{-29} e cm, and interpret this as
      a new upper bound, |d(199Hg)|<3.1x10;{-29} e cm (95% C.L.). This result improves
      our previous 199Hg limit by a factor of 7, and can be used to set new constraints
      on CP violation in physics beyond the standard model.

PMID- 19392102
TI  - Common origin for neutrino anarchy and charged hierarchies.
AB  - The generation of exponential flavor hierarchies from extra-dimensional wave
      function overlaps is reexamined. We find, surprisingly, that the coexistence of
      anarchic fermion mass matrices with such hierarchies is intrinsic and natural to
      this setting. The salient features of charged fermion and neutrino masses and
      mixings can thereby be captured within a single framework. Both Dirac and
      Majorana neutrinos can be realized. Implications for a variety of weak-scale
      scenarios, including warped compactification and supersymmetry, are discussed.
      When the new weak-scale physics is sensitive to the origin of flavor structure,
      Dirac neutrinos are preferred.

PMID- 19392103
TI  - Unexplained excess of electronlike events from a 1-GeV neutrino beam.
AB  - The MiniBooNE Collaboration observes unexplained electronlike events in the
      reconstructed neutrino energy range from 200 to 475 MeV. With 6.46x10;{20}
      protons on target, 544 electronlike events are observed in this energy range,
      compared to an expectation of 415.2+/-43.4 events, corresponding to an excess of
      128.8+/-20.4+/-38.3 events. The shape of the excess in several kinematic
      variables is consistent with being due to either nu_{e} and nu[over ]_{e} charged
      current scattering or nu_{mu} neutral-current scattering with a photon in the
      final state. No significant excess of events is observed in the reconstructed
      neutrino energy range from 475 to 1250 MeV, where 408 events are observed
      compared to an expectation of 385.9+/-35.7 events.

PMID- 19392107
TI  - Di-jet conical correlations associated with heavy quark jets in anti-de sitter
      space/conformal field theory correspondence.
AB  - We show that far zone Mach and diffusion wake "holograms" produced by supersonic
      strings in anti-de Sitter space/conformal field theory (AdS/CFT) correspondence
      do not lead to observable conical angular correlations in the strict N_{c}-
      >infinity supergravity limit if Cooper-Frye hadronization is assumed. However, a
      special nonequilibrium "neck" zone near the jet is shown to produce an apparent
      sonic boom azimuthal angle distribution that is roughly independent of the heavy
      quark's velocity. Our results indicate that a measurement of the dependence of
      the away-side correlations on the velocity of associated identified heavy quark
      jets at the BNL Relativistic Heavy Ion Collider and CERN LHC will provide a
      direct test of the nonperturbative dynamics involved in the coupling between jets
      and the strongly coupled quark-gluon plasma implied by AdS/CFT correspondence.

PMID- 19392108
TI  - First demonstration of electron scattering using a novel target developed for
      short-lived nuclei.
AB  - We carried out a demonstrative electron scattering experiment using a novel ion
      trap target exclusively developed for short-lived highly unstable nuclei. Using
      stable 133Cs ion as a target, this experiment completely mimicked electron
      scattering off short-lived nuclei. Achieving a luminosity higher than 10;{26}
      cm;{-2} s;{-1} with around only 10;{6} trapped ions on the electron beam, the
      angular distribution of elastic scattering was successfully measured. This
      experiment clearly demonstrates that electron scattering off rarely produced
      short-lived nuclei is practical with this target technique.

PMID- 19392109
TI  - Nondispersing Bohr wave packets.
AB  - Long-lived, nondispersing circular, or Bohr, wave packets are produced starting
      from Li Rydberg atoms by exposing them first to a linearly polarized microwave
      field at the orbital frequency, 17.6 GHz at principal quantum number n=72, which
      locks the electron's motion into an approximately linear orbit in which the
      electron oscillates in phase with the microwave field. The microwave polarization
      is changed to circular polarization slowly compared to the orbital frequency, and
      the electron's motion follows, resulting in a nondispersing Bohr wave packet.

PMID- 19392105
TI  - Search for the photoexcitation of exotic mesons in the pi+pi+pi- system.
AB  - A search for exotic mesons in the pi;{+}pi;{+}pi;{-} system photoproduced by the
      charge exchange reaction gammap-->pi;{+}pi;{+}pi;{-}(n) was carried out by the
      CLAS Collaboration at Jefferson Lab. A tagged-photon beam with energies in the
      4.8 to 5.4 GeV range, produced through bremsstrahlung from a 5.744 GeV electron
      beam, was incident on a liquid-hydrogen target. A partial wave analysis was
      performed on a sample of 83 000 events, the highest such statistics to date in
      this reaction at these energies. The main objective of this study was to look for
      the photoproduction of an exotic J;{PC}=1;{-+} resonant state in the 1 to 2 GeV
      mass range. Our partial wave analysis shows production of the a_{2}(1320) and the
      pi_{2}(1670) mesons, but no evidence for the a_{1}(1260), nor the pi_{1}(1600)
      exotic state at the expected levels. An upper limit of 13.5 nb is determined for
      the exotic pi_{1}(1600) cross section, less than 2% of the a_{2}(1320)
      production.

PMID- 19392110
TI  - Plateau structure in resonant laser-assisted electron-atom scattering.
AB  - Orders of magnitude increases are predicted in the cross sections for electron
      atom scattering accompanied by absorption or emission of n laser photons for
      incident electron energies at which the electron, by emitting micro laser
      photons, can be captured by the atom to form a negative ion. Enhancements are
      most significant in the plateau region (n>>micro) of the scattered electron
      spectrum, whose shape is predicted to replicate that of the ion's (n+micro)
      photon detachment spectrum.

PMID- 19392104
TI  - Measurement of direct f0(980) photoproduction on the proton.
AB  - We report on the results of the first measurement of exclusive f_{0}(980) meson
      photoproduction on protons for E_{gamma}=3.0-3.8 GeV and -t=0.4-1.0 GeV2. Data
      were collected with the CLAS detector at the Thomas Jefferson National
      Accelerator Facility. The resonance was detected via its decay in the pi;{+}pi;{
      } channel by performing a partial wave analysis of the reaction gammap-
      >ppi;{+}pi;{-}. Clear evidence of the f_{0}(980) meson was found in the
      interference between P and S waves at M_{pi;{+}pi;{-}} approximately 1 GeV. The S
      wave differential cross section integrated in the mass range of the f_{0}(980)
      was found to be a factor of about 50 smaller than the cross section for the rho
      meson. This is the first time the f_{0}(980) meson has been measured in a
      photoproduction experiment.

PMID- 19392111
TI  - Scheme to probe optomechanical correlations between two optical beams down to the
      quantum level.
AB  - The quantum effects of radiation pressure are expected to limit the sensitivity
      of second-generation gravitational-wave interferometers. Though ubiquitous, such
      effects are so weak that they have not been experimentally demonstrated yet.
      Using a high-finesse optical cavity and a classical intensity noise, we have
      demonstrated radiation-pressure induced correlations between two optical beams
      sent into the same moving mirror cavity. Our scheme can be used to retrieve weak
      correlations at the quantum level and has applications both in high-sensitivity
      measurements and in quantum optics.

PMID- 19392112
TI  - Actively tailored spatiotemporal images of quantum interference on the picometer
      and femtosecond scales.
AB  - Interference fringes of quantum waves weave highly regular space-time images,
      which could be seen in various wave systems such as wave packets in atoms and
      molecules, Bose-Einstein condensates, and fermions in a box potential. We have
      experimentally designed and visualized spatiotemporal images of dynamical quantum
      interferences of two counterpropagating nuclear wave packets in the iodine
      molecule; the wave packets are generated with a pair of femtosecond laser pulses
      whose relative phase is locked within the attosecond time scale. The design of
      the image has picometer and femtosecond resolutions, and changes drastically as
      we change the relative phase of the laser pulses, providing a direct
      spatiotemporal control of quantum interferences.

PMID- 19392113
TI  - Observation of electronic structure minima in high-harmonic generation.
AB  - We report detailed measurements of the high-harmonic spectra generated from argon
      atoms. The spectra exhibit a deep minimum that is shown to be independent of the
      laser intensity, and is thus a clear measure of the electronic structure of the
      atom. We show that exact field-free continuum wave functions reproduce the
      minimum, but plane wave and Coulomb wave functions do not. This remarkable
      observation suggests that electronic structure can be accurately determined in
      high-harmonic experiments despite the presence of the strong laser field. Our
      results clarify the relation between high-harmonic generation and photoelectron
      spectroscopy. The use of exact continuum functions also resolves the ambiguity
      associated with the choice of the dispersion relation.

PMID- 19392114
TI  - Transporting an Image through a Subwavelength Hole.
AB  - The manipulation of optical waves in the subwavelength scale is limited by
      diffraction. In the vicinity of a narrow aperture, the amplitude of the electric
      field is approximately uniform and the transmissivity is extremely low. Here we
      show that despite these fundamental constraints it may be possible to transport
      and redirect a complex electromagnetic image through a tiny subwavelength hole
      with diameter considerably smaller than the diameter of the image, without losing
      the subwavelength details. The proposed concepts hold promise for an
      unprecedented manipulation of the electromagnetic and optical fields in the
      nanoscale with potential applications in imaging and sensing.

PMID- 19392115
TI  - Reliable logic circuit elements that exploit nonlinearity in the presence of a
      noise floor.
AB  - The response of a noisy nonlinear system to deterministic input signals can be
      enhanced by cooperative phenomena. We show that when one presents two square
      waves as input to a two-state system, the response of the system can produce a
      logical output (NOR/OR) with a probability controlled by the noise intensity. As
      one increases the noise (for fixed threshold or nonlinearity), the probability of
      the output reflecting a NOR/OR operation increases to unity and then decreases.
      Changing the nonlinearity (or the thresholds) of the system changes the output
      into another logic operation (NAND/AND) whose probability displays analogous
      behavior. The interplay of nonlinearity and noise can yield logic behavior, and
      the emergent outcome of such systems is a logic gate. This "logical stochastic
      resonance" is demonstrated via an experimental realization of a two-state system
      with two (adjustable) thresholds.

PMID- 19392116
TI  - Statistical ensemble inequivalence and bicritical points for two-dimensional
      flows and geophysical flows.
AB  - A theoretical description for the equilibrium states of a large class of models
      of two-dimensional and geophysical flows is presented. A statistical ensemble
      equivalence is found to exist generically in these models, related to the
      occurrence of peculiar phase transitions in the flow topology. The first example
      of a bicritical point (a bifurcation from a first toward two second order phase
      transitions) in the context of systems with long-range interactions is reported.
      Academic ocean models, the Fofonoff flows, are studied in the perspective of
      these results.

PMID- 19392117
TI  - Satellite Formation during Coalescence of Unequal Size Drops.
AB  - The coalescence of a drop with a flat liquid surface pinches off a satellite from
      its top, in the well-known coalescence cascade, whereas the coalescence of two
      equally sized drops does not appear to leave such a satellite. Herein we perform
      experiments to identify the critical diameter ratio of two drops, above which a
      satellite is produced during their coalescence. We find that the critical parent
      ratio is as small as 1.55, but grows monotonically with the Ohnesorge number. The
      daughter size is typically about 50% of the mother drop. However, we have
      identified novel pinch-off dynamics close to the critical size ratio, where the
      satellite does not fully separate, but rather goes directly into a second stage
      of the coalescence cascade, thus generating a much smaller satellite droplet.

PMID- 19392118
TI  - Bistable heat transfer in a nanofluid.
AB  - Heat convection in water can be suppressed by adding a small amount of highly
      thermophilic nanoparticles. We show that such suppression is not effective when a
      suspension with uniform concentration of nanoparticles is suddenly heated from
      below. At Rayleigh numbers smaller than a sample dependent threshold Ra;{*} we
      observe transient oscillatory convection. Unexpectedly, the duration of
      convection diverges at Ra;{*}. Above Ra;{*} oscillatory convection becomes
      permanent and the heat transferred exhibits bistability. Our results are
      explained only partially and qualitatively by existing theories.

PMID- 19392119
TI  - Maximum achievable beam brightness from photoinjectors.
AB  - Electron injectors delivering relativistic electron beams with very high
      brightness are essential for a number of current and proposed electron
      accelerator applications. These high brightness beams are generally produced from
      photoemission cathodes. We formulate a limit on the electron beam brightness from
      such cathodes set by the transverse thermal energy of the electrons leaving the
      photocathode and the accelerating field at the cathode. Two specific examples-
      direct measurement of the transverse phase space of a space charge dominated beam
      from a high-voltage photoemission electron gun and a numerical optimization of
      the same at a higher gun voltage--illustrate the importance of this limit.

PMID- 19392120
TI  - Relativistic positron creation using ultraintense short pulse lasers.
AB  - We measure up to 2x10;{10} positrons per steradian ejected out the back of
      approximately mm thick gold targets when illuminated with short ( approximately 1
      ps) ultraintense ( approximately 1x10;{20} W/cm;{2}) laser pulses. Positrons are
      produced predominately by the Bethe-Heitler process and have an effective
      temperature of 2-4 MeV, with the distribution peaking at 4-7 MeV. The angular
      distribution of the positrons is anisotropic. Modeling based on the measurements
      indicate the positron density to be approximately 10;{16} positrons/cm;{3}, the
      highest ever created in the laboratory.

PMID- 19392121
TI  - Observation of large-scale density cavities and parametric-decay instabilities in
      the high-altitude discrete auroral ionosphere under pulsed electromagnetic
      radiation.
AB  - A large density cavity that measured 2000 km across and 500 km in height was
      observed by DEMETER and Formosat/COSMIC satellites in temporal and spatial
      relation to a new mode of propagation of electromagnetic (em) pulses between
      discrete magnetic field-aligned auroral plasmas to high altitudes. Recorded
      positive plasma potential from satellite probes is consistent with the expulsion
      of electrons in the creation of density cavities. High-frequency decay spectra
      support the concept of parametric instabilities fed by free energy sources.

PMID- 19392122
TI  - Spatially resolved temperature measurements of electrically heated carbon
      nanotubes.
AB  - Spatially resolved Raman spectra of individual pristine suspended carbon
      nanotubes are observed under electrical heating. The Raman G+ and G- bands show
      unequal temperature profiles. The preferential heating is more pronounced in
      short nanotubes (2 microm) than in long nanotubes (5 microm). These results are
      understood in terms of the decay and thermalization of nonequilibrium phonons,
      revealing the mechanism of thermal transport in these devices. The measurements
      also enable a direct estimate of thermal contact resistances and the spatial
      variation of thermal conductivity.

PMID- 19392123
TI  - Transverse acoustic excitations in liquid Ga.
AB  - The transverse acoustic excitation modes were detected by inelastic x-ray
      scattering in liquid Ga in the Q range above 9 nm(-1) although liquid Ga is
      mostly described by a hard-sphere liquid. An ab initio molecular dynamics
      simulation clearly supports this finding. From the detailed analysis for the
      S(Q,omega) spectra with a good statistic quality, the lifetime of 0.5 ps and the
      propagating length of 0.4-0.5 nm can be estimated for the transverse acoustic
      phonon modes, which may correspond to the lifetime and size of cages formed
      instantaneously in liquid Ga.

PMID- 19392106
TI  - Measurement of resonance parameters of orbitally excited narrow B0 mesons.
AB  - We report a measurement of resonance parameters of the orbitally excited (L=1)
      narrow B0 mesons in decays to B;{(*)+}pi;{-} using 1.7 fb;{-1} of data collected
      by the CDF II detector at the Fermilab Tevatron. The mass and width of the
      B_{2};{*0} state are measured to be m(B_{2};{*0})=5740.2_{-1.8};{+1.7}(stat)
      0.8+0.9(syst) MeV/c;{2} and Gamma(B_{2};{*0})=22.7_{-3.2};{+3.8}(stat)
      10.2+3.2(syst) MeV/c;{2}. The mass difference between the B_{2};{*0} and B10
      states is measured to be 14.9_{-2.5};{+2.2}(stat)-1.4+1.2(syst) MeV/c;{2},
      resulting in a B10 mass of 5725.3_{-2.2};{+1.6}(stat)-1.5+1.4(syst) MeV/c;{2}.
      This is currently the most precise measurement of the masses of these states and
      the first measurement of the B_{2};{*0} width.

PMID- 19392124
TI  - Nanoscale chemical imaging by scanning tunneling microscopy assisted by
      synchrotron radiation.
AB  - Nanoscale chemical imaging using scanning tunneling microscopy is demonstrated
      with a core-level excitation of the probed element by a synchrotron radiation
      light. Pronounced element-specific contrasts were observed in the spatial
      resolution of approximately 10 nm on checkerboard-patterned Ni and Fe samples in
      differential photoinduced current images taken with the scanning tunneling
      microscopy tip under the synchrotron radiation irradiation whose photon energies
      are above and below the Ni (Fe) L absorption edge. The local detection of the
      photoinduced secondary electrons through the surface barrier lowered by the
      proximate tip and/or via the tunneling process probably plays an important role
      in achieving the high-spatial resolution.

PMID- 19392125
TI  - Critical behavior in ferroelectrics from first principles.
AB  - We report first-principles-based calculations, combined with an efficient Monte
      Carlo technique, that undoubtedly show that Pb(Zr0.5Ti0.5)O3, one of the most
      important ferroelectrics to date, adopts critical behavior that strongly deviates
      from the classical mean-field approach while being, in fact, consistent with the
      3D-random Ising universality class.

PMID- 19392126
TI  - Causality in condensates: gray solitons as relics of BEC formation.
AB  - Symmetry breaking during phase transitions can lead to the formation of
      topological defects (such as vortex lines in superfluids). However, the usually
      studied Bose-Einstein condensates (BECs) have the shape of a cigar, a geometry
      that impedes vortex formation, survival, and detection. I show that, in elongated
      traps, one can expect the formation of gray solitons (long-lived, nontopological
      "phase defects") as a result of the same mechanism. Their number will rise
      approximately in proportion to the transition rate. This steep rise is due to the
      increasing size of the region of the BEC cigar where the phase of the condensate
      wave function is chosen locally (rather than passed on from the already formed
      BEC).

PMID- 19392127
TI  - Turning carbon nanotubes from exceptional heat conductors into insulators.
AB  - Thermal conductivity (kappa) of isolated carbon nanotubes (CNTs) is higher than
      the kappa of diamond; however, in this Letter we show that the kappa of a packed
      bed of three-dimensional random networks of single and multiwall CNTs is smaller
      than that of thermally insulating amorphous polymers. The thermoelectric power
      (Sigma) of the random network of CNTs was also measured. The Sigma of a single
      wall nanotube network is very similar to that of isolated nanotubes and, in
      contrast with kappa, Sigma shows a strong dependence on the tube diameter.

PMID- 19392128
TI  - Measuring changes in surface potential as two charged bodies approach in
      electrolyte solution.
AB  - Combining atomic force microscopy with an ion-sensitive field effect transistor
      we provide a novel potentiometer capable of measuring a surface potential change
      as small as 100 microV at 0.2 nm spatial resolution when two charged bodies
      approach in an electrolyte solution. The surface potential measured when two
      silica surfaces approach deviates significantly from values inferred indirectly
      by conventional analysis of force curves. The new data elucidate the way charge
      redistributes between two nonidentical surfaces and allow clear separation of
      electrostatics from other contributions to the interaction such as van der Waals
      and hydration forces.

PMID- 19392129
TI  - Bright beaches of nanoscale potassium islands on graphite in STM imaging.
AB  - We demonstrate, via scanning tunneling microscopy (STM) measurements performed at
      48 K, the existence of "bright beaches" at the edges of K islands (diameter
      approximately 5-500 nm) on the graphite surface. The enhanced tunneling current
      is only observed in monolayer-high islands on graphite, and not in islands of
      similar geometry on top of a K monolayer film. First-principles density
      functional calculations and STM simulations suggest that this is an STM field
      effect, which appears as the positive tip attracts donated electrons back to the
      metallic K islands. The restored charge accumulates preferentially at the island
      edges.

PMID- 19392130
TI  - Liquid Spreading under Nanoscale Confinement.
AB  - Dynamic atomic force microscopy in the noncontact regime is used to study the
      morphology of a nonvolatile liquid (squalane) as it spreads along wettable
      nanostripes embedded in a nonwettable surface. Results show that the liquid
      profile depends on the amount of lateral confinement imposed by the nanostripes,
      and it is truncated at the microscopic contact line in good qualitative agreement
      with classical mesoscale hydrodynamics. However, the width of the contact line is
      found to be significantly larger than expected theoretically. This behavior may
      originate from small chemical inhomogeneity of the patterned stripes as well as
      from thermal fluctuations of the contact line.

PMID- 19392131
TI  - Thermodynamics and kinetics of graphene growth on SiC(0001).
AB  - The formation of surface phases on the Si-terminated SiC(0001) surface, from the
      Si-rich (3x3) structure, through the intermediate (1x1) and (sqrt[3]xsqrt[3])-R30
      degrees structures, to the C-rich (6sqrt[3]x6sqrt[3]) phase, and finally
      epitaxial graphene, has been well documented. But the thermodynamics and kinetics
      of these phase formations are poorly understood. Using in situ low energy
      electron microscopy, we show how the phase transformation temperatures can be
      shifted over several hundred degrees Celsius, and the phase transformation time
      scales reduced by several orders of magnitude, by balancing the rate of Si
      evaporation with an external flux of Si. Detailed insight in the thermodynamics
      allows us to dramatically improve the morphology of the final C-rich surface
      phases, including epitaxial graphene.

PMID- 19392132
TI  - Evidence for the predominance of subsurface defects on reduced anatase TiO2(101).
AB  - Scanning tunneling microscopy (STM) images taken on a freshly cleaved anatase
      TiO2(101) sample show an almost perfect surface with very few subsurface
      impurities and adsorbates. Surface oxygen vacancies are not typically present but
      can be induced by electron bombardment. In contrast, a reduced anatase (101)
      crystal shows isolated as well as ordered intrinsic subsurface defects in STM,
      consistent with density functional theory (DFT) calculations which predict that O
      vacancies (V_{O}'s) at subsurface and bulk sites are significantly more stable
      than on the surface.

PMID- 19392133
TI  - Localization and the Kosterlitz-Thouless transition in disordered graphene.
AB  - We investigate disordered graphene with strong long-range impurities. Contrary to
      the common belief that delocalization should persist in such a system against any
      disorder, as the system is expected to be equivalent to a disordered two
      dimensional Dirac fermionic system, we find that states near the Dirac points are
      localized for sufficiently strong disorder (therefore inevitable intervalley
      scattering) and the transition between the localized and delocalized states is of
      Kosterlitz-Thouless type. Our results show that the transition originates from
      bounding and unbounding of local current vortices.

PMID- 19392134
TI  - Theory of spin exciton in the Kondo semiconductor YbB12.
AB  - The Kondo semiconductor YbB12 exhibits a spin and charge gap of approximately 15
      meV. Close to the gap energy narrow dispersive collective excitations were
      identified by previous inelastic neutron scattering experiments. We present a
      theoretical analysis of these excitations. Starting from a periodic Anderson
      model for crystalline-electric-field- (CEF) split 4f states we derive the
      hybridized quasiparticle bands in slave boson mean-field approximation and
      calculate the momentum dependent dynamical susceptibility in random phase
      approximation. We show that a small difference in the hybridization of the two
      CEF (quasi-) quartets leads to the appearance of two dispersive spin resonance
      excitations at the continuum threshold. Our theoretical analysis explains the
      most salient features of previously unexplained experiments on the magnetic
      excitations of YbB12.

PMID- 19392135
TI  - Probing the neutral edge modes in transport across a point contact via thermal
      effects in the Read-Rezayi non-Abelian quantum Hall states.
AB  - Non-Abelian quantum Hall states are characterized by the simultaneous appearance
      of charge and neutral gapless edge modes, with the structure of the latter being
      intricately related to the existence of bulk quasiparticle excitations obeying
      non-Abelian statistics. Here we propose a scenario for detecting the neutral
      modes by having two point contacts in series separated by a distance set by the
      thermal equilibration length of the charge mode. We show that by using the first
      point contact as a heating device, the excess charge noise measured at the second
      point contact carries a nontrivial signature of the presence of the neutral mode.
      We also obtain explicit expressions for the thermal conductance and corresponding
      Lorentz number for transport across a quantum point contact between two edges
      held at different temperatures and chemical potentials.

PMID- 19392136
TI  - Quantum phase transition in a 1D transport model with boson-affected hopping:
      Luttinger liquid versus charge-density-wave behavior.
AB  - We solve a very general two-channel fermion-boson model describing charge
      transport within some background medium by means of a refined pseudosite density
      matrix renormalization group technique. Performing a careful finite-size scaling
      analysis, we determine the ground-state phase diagram and convincingly prove that
      the model exhibits a metal-insulator quantum phase transition for the half-filled
      band case. In order to characterize the metallic and insulating regimes we
      calculate, besides the local particle densities and fermion-boson correlation
      functions, the kinetic energy, the charge-structure factor, the Luttinger liquid
      charge exponent, and the single-particle excitation gap for a one-dimensional
      infinite system.

PMID- 19392137
TI  - Detection of domain dynamics by high energy photons: proposals in one-dimensional
      photoinduced phase transition systems.
AB  - We propose the detection of domain dynamics in a one-dimensional system by using
      high energy photons such as synchrotron radiation. The domain here means that of
      a different phase formed in the background of an original phase. Using high
      energy photons, it is expected that not only k=0 states with k being the momentum
      of its center of gravity motion, but also finite k states are possible to be
      detected. We theoretically demonstrate how they are observed, with nonresonant
      inelastic x-ray scattering and valence photoemission as concrete examples. In the
      former, we mainly detect charge excitations, particularly, the center of gravity
      and the spatial size of the domain as its basic two degrees of freedom, while, in
      the latter, spin excitations inside the domain also play an essential role.

PMID- 19392138
TI  - Multifractal analysis with the probability density function at the three
      dimensional anderson transition.
AB  - The probability density function (PDF) for critical wave function amplitudes is
      studied in the three-dimensional Anderson model. We present a formal expression
      between the PDF and the multifractal spectrum f(alpha) in which the role of
      finite-size corrections is properly analyzed. We show the non-Gaussian nature and
      the existence of a symmetry relation in the PDF. From the PDF, we extract
      information about f(alpha) at criticality such as the presence of negative
      fractal dimensions and the possible existence of termination points. A PDF-based
      multifractal analysis is shown to be a valid alternative to the standard approach
      based on the scaling of inverse participation ratios.

PMID- 19392139
TI  - Gauge-field rotation of an electrically polarized bose condensate by a radial
      magnetic field.
AB  - Here it is shown that a condensate of electrically polarized bosons subject to a
      radial magnetic field must rotate due to the Aharonov-Bohm effect. As in
      mechanically rotated superfluids, rotation is accompanied by penetration of
      vortices into the condensate at some critical magnetic field. In the case of a
      Bose-condensed exciton cloud in a double-quantum well, a necessary electric
      polarization is provided with spatial separation of electrons and holes forming
      excitons. Penetration of vortices strongly affects the intensity and the angular
      distribution of photoluminescence from the exciton cloud. This effect can be used
      for an experimental manifestation of exciton Bose condensation.

PMID- 19392140
TI  - Initial stages of the contact between a metallic tip and carbon nanotubes.
AB  - We present an experimental and theoretical study of the interaction between a tip
      and single-walled carbon nanotubes (SWCNT) lying on a SiO2 surface. Adhesion and
      jump-to-contact forces (JC) are measured in a high vacuum system for SWCNT with
      diameters (D) ranging from 1.4 to 4.5 nm; we find adhesion forces approximately
      3.2 nN and JC forces approximately 2.4 nN. Simulations yield adhesion forces in
      agreement with experiment showing that for D approximately 1.4 nm half of this
      force is due to tip-SWCNT and tip-SiO2 van der Waals interactions.

PMID- 19392141
TI  - Dynamics of particle-hole pair creation in graphene.
AB  - The process of coherent creation of particle-hole excitations by an electric
      field in graphene is quantitatively described. We calculate the evolution of the
      current density, number of pairs, and energy after switching on the electric
      field. In particular, it leads to a dynamical visualization of universal finite
      resistivity without dissipation in pure graphene. We show that the dc
      conductivity of pure graphene is pi/2e;{2}/h rather than the often cited value of
      4/pie;{2}/h. This value coincides with the ac conductivity calculated and
      measured recently at optical frequencies. The effect of temperature and random
      chemical potential (charge puddles) are considered and explain the recent
      experiment on suspended graphene. A possibility of Bloch oscillations is
      discussed within the tight binding model.

PMID- 19392142
TI  - Quantum nature of two-dimensional electron gas confinement at LaAlO3/SrTiO3
      interfaces.
AB  - We perform density functional calculations to understand the mechanism
      controlling the confinement width of the two-dimensional electron gas (2DEG) at
      LaAlO_{3}/SrTiO_{3} interfaces. We find that the 2DEG confinement can be
      explained by the formation of metal induced gap states (MIGS) in the band gap of
      SrTiO3. These states are formed as the result of quantum-mechanical tunneling of
      the charge created at the interface due to electronic reconstruction. The
      attenuation length of the MIGS into the insulator is controlled by the lowest
      decay-rate evanescent states of SrTiO3, as determined by its complex band
      structure. Our calculations predict that the 2DEG is confined in SrTiO3 within
      about 1 nm at the interface.

PMID- 19392143
TI  - Reduced and projected two-particle entanglement at finite temperatures.
AB  - We present a theory for two-particle entanglement production and detection in
      mesoscopic conductors at finite temperature. The entanglement of the density
      matrix projected out of the emitted many-body state differs from the entanglement
      of the reduced density matrix, detectable by current correlation measurements.
      Under general conditions reduced entanglement constitutes a witness for projected
      entanglement. Applied to the recent experiment [Neder et al., Nature (London)
      448, 333 (2007)10.1038/nature05955] on a fermionic Hanbury Brown Twiss two
      particle interferometer we find that despite an appreciable entanglement
      production in the experiment, the detectable entanglement is close to zero.

PMID- 19392144
TI  - Diameter-dependent electronic transport properties of Au-catalyst/Ge-nanowire
      Schottky diodes.
AB  - We present electronic transport measurements in individual Au-catalyst/Ge
      nanowire interfaces demonstrating the presence of a Schottky barrier.
      Surprisingly, the small-bias conductance density increases with decreasing
      diameter. Theoretical calculations suggest that this effect arises because
      electron-hole recombination in the depletion region is the dominant charge
      transport mechanism, with a diameter dependence of both the depletion width and
      the electron-hole recombination time. The recombination time is dominated by
      surface contributions and depends linearly on the nanowire diameter.

PMID- 19392145
TI  - Valence bond glass theory of electronic disorder and the pseudogap state of high
      temperature cuprate superconductors.
AB  - We show that the low-energy fluctuations of the valence bond due to the
      superexchange are pinned by the electronic disorder from off-stoichiometric
      dopants, leading to a valence bond glass (VBG) pseudogap phase in underdoped high
      T_{c} cuprates. The antinodal Fermi surface sections are gapped out, giving rise
      to a normal state Fermi arc whose length shrinks with underdoping. Below T_{c},
      the superexchange interaction induces a d-wave superconducting gap that coexists
      with the VBG pseudogap. The evolution of the local and momentum-space
      spectroscopy with doping and temperature captures the salient properties of the
      pseudogap phenomena and the electronic disorder.

PMID- 19392146
TI  - Electronic structure and unusual exchange splitting in the spin-density-wave
      state of the BaFe2As2 parent compound of iron-based superconductors.
AB  - The magnetic properties in the parent compounds are often intimately related to
      the microscopic mechanism of superconductivity. Here we report the first direct
      measurements on the electronic structure of a parent compound of the newly
      discovered iron-based superconductor, BaFe2As2, which provides a foundation for
      further studies. We show that the energy of the spin density wave in BaFe2As2 is
      mainly lowered through exotic exchange splitting of the band structure.

PMID- 19392147
TI  - Anisotropy, itineracy, and magnetic frustration in high-Tc iron pnictides.
AB  - Using first-principles density functional theory calculations combined with
      insight from a tight-binding representation, dynamical mean field theory, and
      linear response theory, we have extensively investigated the electronic
      structures and magnetic interactions of nine ferropnictides representing three
      different structural classes. The calculated magnetic interactions are found to
      be short range, and the nearest (J_{1a}) and next-nearest (J2) exchange constants
      follow the universal trend of J_{1a}/2J_{2} approximately 1, despite their
      itinerant origin and extreme sensitivity to the z position of As. These results
      bear on the discussion of itineracy versus magnetic frustration as the key factor
      in stabilizing the superconducting ground state. The calculated spin-wave
      dispersions show strong magnetic anisotropy in the Fe plane, in contrast with
      cuprates.

PMID- 19392148
TI  - Superconducting transition at 38 K in insulating-overdoped La2CuO4
      La1.64Sr0.36CuO4 superlattices: evidence for interface electronic redistribution
      from resonant soft X-ray scattering.
AB  - We use resonant soft x-ray scattering (RSXS) to quantify the hole distribution in
      a superlattice of insulating La2CuO4 (LCO) and overdoped La2-xSrxCuO4 (LSCO).
      Despite its nonsuperconducting constituents, this structure is superconducting
      with T_{c}=38 K. We found that the conducting holes redistribute electronically
      from LSCO to the LCO layers. The LCO layers were found to be optimally doped,
      suggesting they are the main drivers of superconductivity. Our results
      demonstrate the utility of RSXS for separating electronic from structural effects
      at oxide interfaces.

PMID- 19392150
TI  - Inelastic neutron-scattering measurements of a three-dimensional spin resonance
      in the FeAs-based BaFe1.9Ni0.1As2 superconductor.
AB  - We use inelastic neutron scattering to study magnetic excitations of the FeAs
      based superconductor BaFe1.9Ni0.1As2 above and below its T_{c} (=20 K). In
      addition to gradually open a spin gap at the in-plane antiferromagnetic ordering
      wave vector (1, 0, 0), the effect of superconductivity is to form a three
      dimensional resonance with clear dispersion along the c axis. The intensity of
      the resonance develops like a superconducting order parameter, and the mode
      occurs at distinctively different energies at (1, 0, 0) and (1, 0, 1). If the
      resonance energy is associated with the superconducting gap energy Delta, then
      Delta is dependent on the wave vector transfers along the c axis. These results
      suggest that one must be careful in interpreting the superconducting gap energies
      obtained by surface sensitive probes such as scanning tunneling microscopy and
      angle resolved photoemission.

PMID- 19392149
TI  - Two-dimensional resonant magnetic excitation in BaFe1.84Co0.16As2.
AB  - Inelastic neutron scattering measurements on single crystals of superconducting
      BaFe1.84Co0.16As2 reveal a magnetic excitation located at wave vectors (1/2 1/2
      L) in tetragonal notation. On cooling below T_{C}, a clear resonance peak is
      observed at this wave vector with an energy of 8.6(0.5) meV, corresponding to
      4.5(0.3) k_{B}T_{C}. This is in good agreement with the canonical value of 5
      k_{B}T_{C} observed in the cuprates. The spectrum shows strong dispersion in the
      tetragonal plane but very weak dispersion along the c axis, indicating that the
      magnetic fluctuations are two dimensional in nature. This is in sharp contrast to
      the anisotropic three dimensional spin excitations seen in the undoped parent
      compounds.

PMID- 19392151
TI  - Anisotropic electron-phonon coupling and dynamical nesting on the graphene sheets
      in superconducting CaC6 using angle-resolved photoemission spectroscopy.
AB  - We present the first angle-resolved photoemission studies of electronic structure
      in CaC6, a superconducting graphite intercalation compound with T_{c}=11.6 K. We
      find that, contrary to theoretical models, the electron-phonon coupling on the
      graphene-derived Fermi sheets with high-frequency graphene-derived phonons is
      surprisingly strong and anisotropic. The shape of the Fermi surface is found to
      favor a dynamical intervalley nesting via exchange of high-frequency phonons. Our
      results suggest that graphene sheets play a crucial role in superconductivity in
      graphite intercalation compounds.

PMID- 19392152
TI  - Pairing symmetry conversion by spin-active interfaces in magnetic normal-metal
      superconductor junctions.
AB  - We study the proximity-induced superconducting correlations in a normal metal
      connected to a superconductor when the interface between them is spin active and
      the normal metal is ballistic or diffusive. Remarkably, for any interface spin
      polarization there is a critical interface resistance, above which the
      conventional even-frequency proximity component vanishes completely at the
      chemical potential, while the odd-frequency component remains finite. We propose
      a way to unambiguously observe the odd-frequency component.

PMID- 19392153
TI  - Controlled switching of Neel caps in flux-closure magnetic dots.
AB  - While magnetic hysteresis usually considers magnetic domains, the switching of
      the core of magnetic vortices has recently become an active topic. We considered
      Bloch domain walls, which are known to display at the surface of thin films flux
      closure features called Neel caps. We demonstrated the controlled switching of
      these caps under a magnetic field, occurring via the propagation of a surface
      vortex. For this we considered flux-closure states in elongated micron-sized
      dots, so that only the central domain wall can be addressed, while domains remain
      unaffected.

PMID- 19392154
TI  - Observation and coupling of domains in a spin-spiral multiferroic.
AB  - The coexistence, coupling, and manipulation of magnetic spiral domains and
      magnetically induced ferroelectric domains are spatially resolved by optical
      second harmonic generation in multiferroic MnWO4. Eight types of magnetic domains
      couple to two ferroelectric domains. An electric field uniquely creates a
      magnetic single-domain state. A magnetic field quenches the spontaneous
      polarization while retaining its magnetic origin so that the ferroelectric
      domains are concealed instead of destroyed.

PMID- 19392155
TI  - Magnetic and magnetoelectric excitations in TbMnO3.
AB  - Magnetic and magnetoelectric excitations in the multiferroic TbMnO3 have been
      investigated at terahertz frequencies. Using different experimental geometries we
      can clearly separate the electroactive excitations (electromagnons) from the
      magnetoactive modes, i.e., antiferromagnetic resonances. Two antiferromagnetic
      resonances were found to coincide with electromagnons. This indicates that both
      excitations belong to the same mode and the electromagnons can be excited by a
      magnetic ac field as well. In spite of the 90 degrees rotation of the magnetic
      cycloid in external magnetic fields, the electromagnons are observable for
      electric ac fields parallel to the a axis only.

PMID- 19392156
TI  - Direct observation of magnon fractionalization in the quantum spin ladder.
AB  - We measure by inelastic neutron scattering the spin excitation spectra as a
      function of applied magnetic field in the quantum spin-ladder material
      (C5H12N)2CuBr4. Discrete magnon modes at low fields in the quantum disordered
      phase and at high fields in the saturated phase contrast sharply with a spinon
      continuum at intermediate fields characteristic of the Luttinger-liquid phase. By
      tuning the magnetic field, we drive the fractionalization of magnons into spinons
      and, in this deconfined regime, observe both commensurate and incommensurate
      continua.

PMID- 19392157
TI  - Excitation of dark plasmons in metal nanoparticles by a localized emitter.
AB  - We study theoretically a dipole emitter placed near a metal nanoparticle and near
      small chains of two and three nanoparticles. The emitter can efficiently excite
      dark, or nonradiative, surface-plasmon modes in the nanostructures, in addition
      to the well-known bright modes. In the case of coupled nanoparticles, the origins
      of the bright and dark modes can be understood in the context of plasmon
      hybridization. Excitation of dark modes in nanoparticle chains allows for
      subwavelength guiding of optical energy with no radiative losses and thus with
      improved propagation lengths.

PMID- 19392158
TI  - Optical generation of gigahertz-frequency shear acoustic waves in liquid
      glycerol.
AB  - Picosecond laser ultrasonic techniques for acoustic wave generation and detection
      have been employed to probe shear acoustic waves in liquid glycerol at gigahertz
      frequencies. The experimental approach uses a unique laser pulse shaping
      technique and a crystallographically canted metal layer to generate frequency
      tunable transverse acoustic waves, and uses time-domain coherent Brillouin
      scattering to detect the waves after they propagate through a liquid layer and
      into a solid substrate. A linear frequency dependence is found for both the shear
      speed and attenuation rate in glycerol.

PMID- 19392159
TI  - Tunable optical gap at a fixed lattice constant in group-IV semiconductor alloys.
AB  - A direct absorption edge tunable between 0.8 and approximately 1.4 eV is
      demonstrated in strain-free ternary Ge_{1-x-y}Si_{x}Sn_{y} alloys epitaxially
      grown on Ge-buffered Si. This decoupling of electronic structure and lattice
      parameter-unprecedented in group-IV alloys-opens up new possibilities in silicon
      photonics, particularly in the field of photovoltaics. The compositional
      dependence of the direct band gap in Ge_{1-x-y}Si_{x}Sn_{y} exhibits a
      nonmonotonic behavior that is explained in terms of coexisting small and giant
      bowing parameters in the two-dimensional compositional space.

PMID- 19392160
TI  - Absence of critical thickness in an ultrathin improper ferroelectric film.
AB  - We study the ferroelectric stability and surface structural properties of an
      oxygen-terminated hexagonal YMnO3 ultrathin film using density functional theory.
      Under an open circuit boundary condition, the ferroelectric state with the
      spontaneous polarization normal to the (0001) surface is found to be metastable
      in a single domain state despite the presence of a depolarizing field. Our
      results highlight that improper ferroelectric ultrathin films can have rather
      unique properties that are distinct from those of very thin films of ordinary
      ferroelectrics.

PMID- 19392161
TI  - Avoiding the polarization catastrophe in LaAlO3 overlayers on SrTiO3(001) through
      polar distortion.
AB  - A pronounced uniform polar distortion extending over several unit cells enables
      thin LaAlO3 overlayers on SrTiO3(001) to counteract the charge dipole and thereby
      neutralize the "polarization catastrophe" that is suggested by simple ion
      counting. This unanticipated mechanism, obtained from density functional theory
      calculations, allows several unit cells of the LaAlO3 overlayer to remain
      insulating (hence, fully ionic). The band gap of the system, defined by occupied
      O 2p states at the surface and unoccupied Ti 3d states at the interface in some
      cases approximately 20 A distant, decreases with increasing thickness of the
      LaAlO3 film before an insulator-to-metal transition and a crossover to an
      electronic reconstruction occurs at around five monolayers of LaAlO3.

PMID- 19392162
TI  - Electric polarization in a Chern insulator.
AB  - We extend the Berry-phase concept of polarization to insulators having a nonzero
      value of the Chern invariant. The generalization to such Chern insulators
      requires special care because of the partial occupation of chiral edge states. We
      show how the integrated bulk current arising from an adiabatic evolution can be
      related to a difference of bulk polarizations. We also show how the surface
      charge can be related to the bulk polarization, but only with a knowledge of the
      wave vector at which the occupancy of the edge state is discontinuous.
      Furthermore, we present numerical calculations on a model Hamiltonian to provide
      additional support for our analytic arguments.

PMID- 19392163
TI  - Trafficlike collective movement of ants on trails: absence of a jammed phase.
AB  - We report experimental results on unidirectional trafficlike collective movement
      of ants on trails. Our work is primarily motivated by fundamental questions on
      the collective spatiotemporal organization in systems of interacting motile
      constituents driven far from equilibrium. Making use of the analogies with
      vehicular traffic, we analyze our experimental data for the spatiotemporal
      organization of ants on a trail. From this analysis, we extract the flow-density
      relation as well as the distributions of velocities of the ants and distance
      headways. Some of our observations are consistent with our earlier models of ant
      traffic, which are appropriate extensions of the asymmetric simple exclusion
      process. In sharp contrast to highway traffic and most other transport processes,
      the average velocity of the ants is almost independent of their density on the
      trail. Consequently, no jammed phase is observed.

PMID- 19392164
TI  - Equilibrium and nonequilibrium effects in the collapse of a model polypeptide.
AB  - We present results of molecular simulations of a model polypeptide whose
      hydrophobic collapse proceeds as a cascade of downhill transitions between
      distinct intermediate states. Different intermediates are stabilized by means of
      appropriate harmonic constraints, allowing explicit calculation of the
      equilibrium free energy landscape. Nonequilibrium collapse trajectories are
      simulated independently and compared to diffusion on the calculated free energy
      surface. We find that collapse generally adheres to this surface, but
      quantitative agreement is complicated by nonequilibrium effects and by dependence
      of the diffusion coefficient on position on the surface.

PMID- 19392165
TI  - Particle pressure in a sheared suspension: a bridge from osmosis to granular
      dilatancy.
AB  - The normal stress exerted by particles in a sheared suspension is measured by
      analogy with a method used to measure osmotic pressure in solutions. Particles in
      a liquid are confined by a fine screen to a gap between two vertical concentric
      cylinders, the inner of which rotates. Pressure in the liquid is sensed either by
      a manometer or by a pressure transducer across the screen. The particles are
      large enough so that Brownian motion and equilibrium osmotic pressure are
      vanishingly small. The measured pressure yields the shear-induced particle
      pressure Pi, the nonequilibrium continuation of equilibrium osmotic pressure. For
      volume fractions 0.3< or =varphi< or =0.5, Pi is strongly dependent on varphi,
      and linear in shear rate. Comparisons of the measured particle pressure with
      modeling and simulation show good agreement.

PMID- 19392166
TI  - Pair potential of charged colloidal stars.
AB  - We report on the construction of colloidal stars: 1 microm polystyrene beads
      grafted with a dense brush of 1 microm long and 10 nm wide charged semiflexible
      filamentous viruses. The pair interaction potentials of colloidal stars are
      measured using an experimental implementation of umbrella sampling, a technique
      originally developed in computer simulations in order to probe rare events. The
      influence of ionic strength and grafting density on the interaction is measured.
      Good agreements are found between the measured interactions and theoretical
      predictions based upon the osmotic pressure of counterions.

PMID- 19392167
TI  - Hydrodynamic selection of the kinetic pathway of a polymer coil-globule
      transition.
AB  - Recently, the role of hydrodynamic interactions in the selection of a kinetic
      pathway for phase transitions has attracted considerable attention. Here we study
      this problem numerically by taking as an example a coil-globule transition of a
      single polymer, which is a prototype model of protein folding. When a swollen
      polymer collapses into a globule state, hydrodynamic interactions accelerate the
      transition. We find, on the other hand, that when a rather compact polymer
      collapses into the same final state, hydrodynamic interactions decelerate the
      transition due to a slow squeezing process of the solvent. We reveal that the
      degree of the initial enhancement of anisotropy of the polymer configuration
      determines whether hydrodynamic interactions accelerate or decelerate the
      collapsing dynamics. We also discuss the possible relevance of squeezing flow
      effects in protein folding.

PMID- 19392168
TI  - Molecular dynamics simulations of optimal dynamic uncharged polymer coatings for
      quenching electro-osmotic flow.
AB  - The suppression of electro-osmotic flow (EOF) through the use of a dynamically
      adsorbed polymer coating is a widely used technique in microfluidic devices.
      Recent experimental evidence has suggested that the most effective coatings are
      those which are only weakly adsorbed to the surface. We report molecular dynamics
      simulation results which show that the optimal adsorption strength for the
      suppression of EOF is around the transition for adsorption of the polymer. Our
      results should help to guide the design of novel polymer coatings for improved
      quenching of EOF.

PMID- 19392169
TI  - Axisymmetric granular collapse: a transient 3D flow test of viscoplasticity.
AB  - A viscoplastic continuum theory has recently been proposed to model dense,
      cohesionless granular flows [P. Jop, Nature (London) 441, 727
      (2006)10.1038/nature04801]. We confront this theory for the first time with a
      transient, three-dimensional flow situation--the simple collapse of a cylinder of
      granular matter onto a horizontal plane--by extracting stress and strain rate
      tensors directly from soft particle simulations. These simulations faithfully
      reproduce the different flow regimes and capture the observed scaling laws for
      the final deposit. Remarkably, the theoretical hypothesis that there is a simple
      stress-strain rate tensorial relationship does seem to hold across the whole flow
      even close to the rough boundary provided the flow is dense enough. These
      encouraging results suggest viscoplastic theory is more generally applicable to
      transient, multidirectional, dense flows and open the way for quantitative
      predictions in real applications.

PMID- 19392170
TI  - Comment on "role of electron-hole pair excitations in the dissociative adsorption
      of diatomic molecules on metal surfaces".

PMID- 19392174
TI  - Short-time enhancement of the decay of coherent excitations in Bose-Einstein
      Condensates.
AB  - We study, both experimentally and theoretically, short-time modifications of the
      decay of excitations in a Bose-Einstein Condensate (BEC) embedded in an optical
      lattice. Strong enhancement of the decay is observed compared to the Golden Rule
      results. This enhancement of decay increases with the lattice depth. It indicates
      that the description of decay modifications of few-body quantum systems also
      holds for decay of many-body excitations of a BEC.

PMID- 19392172
TI  - Comment on "BCS superconductivity of dirac electrons in graphene layers".

PMID- 19392175
TI  - Emergence of quantum correlations from nonlocality swapping.
AB  - By studying generalized nonsignaling theories, the hope is to find out what makes
      quantum mechanics so special. In the present Letter, we revisit the paradigmatic
      model of nonsignaling boxes and introduce the concept of a genuine box. This will
      allow us to present the first generalized nonsignaling model featuring
      quantumlike dynamics. In particular, we present the coupler, a device enabling
      nonlocality swapping, the analogue of quantum entanglement swapping, as well as
      teleportation. Remarkably, part of the boundary between quantum and post-quantum
      correlations emerges in our study.

PMID- 19392176
TI  - Dynamical typicality of quantum expectation values.
AB  - We show that the vast majority of all pure states featuring a common expectation
      value of some generic observable at a given time will yield very similar
      expectation values of the same observable at any later time. This is meant to
      apply to Schrodinger type dynamics in high dimensional Hilbert spaces. As a
      consequence individual dynamics of expectation values are then typically well
      described by the ensemble average. Our approach is based on the Hilbert space
      average method. We support the analytical investigations with numerics obtained
      by exact diagonalization of the full time-dependent Schrodinger equation for some
      pertinent, abstract Hamiltonian model. Furthermore, we discuss the implications
      for the applicability of projection operator methods with respect to initial
      states, as well as for irreversibility in general.

PMID- 19392177
TI  - Positive phase space transformation incompatible with classical physics.
AB  - Bell conjectured that a positive Wigner function does not allow violation of the
      inequalities imposed by local hidden variable theories. A requirement for this
      conjecture is "when phase space measurements are performed." We introduce the
      theory-independent concept of "operationally local transformations" which refers
      to the change of the switch on a local measurement apparatus. We show that two
      separated parties, performing only phase space measurements on a composite
      quantum system with a positive Wigner function and performing only operationally
      local transformations that preserve this positivity, can nonetheless violate
      Bell's inequality. Such operationally local transformations are realized using
      entangled ancillae.

PMID- 19392178
TI  - Dynamics of a two-dimensional system of quantum dipoles.
AB  - A detailed microscopic analysis of the dynamic structure function S(k,omega) of a
      two-dimensional Bose system of dipoles polarized along the direction
      perpendicular to the plane is presented and discussed. Starting from ground-state
      quantities obtained using a quantum diffusion Monte Carlo algorithm, the density
      density response is evaluated in the context of the correlated basis functions
      (CBF) theory. CBF predicts a sharp peak and a multiexcitation component at higher
      energies produced by the decay of excitations. We discuss the structure of the
      phonon-roton peak and show that the Feynman and Bogoliubov predictions depart
      from the CBF result already at low densities. We finally discuss the emergence of
      a roton in the spectrum, but find the roton energy not low enough to make the
      system unstable under density fluctuations up to the highest density considered
      that is close to the freezing point.

PMID- 19392179
TI  - Density and spin response function of a normal Fermi gas at unitarity.
AB  - Using the Landau theory of Fermi liquids, we calculate the dynamic response of
      both a polarized and an unpolarized normal Fermi gas at zero temperature in the
      strongly interacting regime of large scattering length. We show that at small
      excitation energies the in phase (density) response is enhanced with respect to
      the ideal gas prediction due to the increased compressibility. Vice versa, the
      out of phase (spin) response is quenched as a consequence of the tendency of the
      system to pair opposite spins. The long wavelength behavior of the static
      structure factor is explicitly calculated. The results are compared with the
      predictions in the collisional and superfluid regimes. The emergence of a spin
      zero sound solution in the unpolarized normal phase is explicitly discussed.

PMID- 19392180
TI  - Quantum communication beyond the localization length in disordered spin chains.
AB  - We study the effects of localization on quantum state transfer in spin chains. We
      show how to use quantum error correction and multiple parallel spin chains to
      send a qubit with high fidelity over arbitrary distances, in particular,
      distances much greater than the localization length of the chain.

PMID- 19392181
TI  - Restrictions on transversal encoded quantum gate sets.
AB  - Transversal gates play an important role in the theory of fault-tolerant quantum
      computation due to their simplicity and robustness to noise. By definition,
      transversal operators do not couple physical subsystems within the same code
      block. Consequently, such operators do not spread errors within code blocks and
      are, therefore, fault tolerant. Nonetheless, other methods of ensuring fault
      tolerance are required, as it is invariably the case that some encoded gates
      cannot be implemented transversally. This observation has led to a long-standing
      conjecture that transversal encoded gate sets cannot be universal. Here we show
      that the ability of a quantum code to detect an arbitrary error on any single
      physical subsystem is incompatible with the existence of a universal, transversal
      encoded gate set for the code.

PMID- 19392182
TI  - Alkaline-earth-metal atoms as few-qubit quantum registers.
AB  - We propose and analyze a novel approach to quantum information processing, in
      which multiple qubits can be encoded and manipulated using electronic and nuclear
      degrees of freedom associated with individual alkaline-earth-metal atoms trapped
      in an optical lattice. Specifically, we describe how the qubits within each
      register can be individually manipulated and measured with subwavelength optical
      resolution. We also show how such few-qubit registers can be coupled to each
      other in optical superlattices via conditional tunneling to form a scalable
      quantum network. Finally, potential applications to quantum computation and
      precision measurements are discussed.

PMID- 19392183
TI  - De Finetti representation theorem for infinite-dimensional quantum systems and
      applications to quantum cryptography.
AB  - We show that the quantum de Finetti theorem holds for states on infinite
      dimensional systems, provided they satisfy certain experimentally verifiable
      conditions. This result can be applied to prove the security of quantum key
      distribution based on weak coherent states or other continuous variable states
      against general attacks.

PMID- 19392184
TI  - Purely quantum superadditivity of classical capacities of quantum multiple access
      channels.
AB  - We are studying classical capacities of quantum memoryless multiaccess channels
      in geometric terms and we are revealing a break of additivity of the Holevo-like
      capacity. This effect is a purely quantum mechanical one, since, as we point out,
      the capacity regions of all classical memoryless multiaccess channels are
      additive. It is the first such effect revealed in the field of classical
      information transmission via quantum channels.

PMID- 19392185
TI  - Magnetowave induced plasma wakefield acceleration for ultrahigh energy cosmic
      rays.
AB  - Magnetowave induced plasma wakefield acceleration (MPWA) in a relativistic
      astrophysical outflow has been proposed as a viable mechanism for the
      acceleration of cosmic particles to ultrahigh energies. Here we present
      simulation results that clearly demonstrate the viability of this mechanism for
      the first time. We invoke the high frequency and high speed whistler mode for the
      driving pulse. The plasma wakefield obtained in the simulations compares
      favorably with our newly developed relativistic theory of the MPWA. We show that,
      under appropriate conditions, the plasma wakefield maintains very high coherence
      and can sustain high-gradient acceleration over hundreds of plasma skin depths.
      Invoking active galactic nuclei as the site, we show that MPWA production of
      ultrahigh energy cosmic rays beyond ZeV (10{21} eV) is possible.

PMID- 19392187
TI  - Instability of anisotropic cosmological solutions supported by vector fields.
AB  - Models with vector fields acquiring a nonvanishing vacuum expectation value along
      one spatial direction have been proposed to sustain a prolonged stage of
      anisotropic accelerated expansion. Such models have been used for realizations of
      early time inflation, with a possible relation to the large scale cosmic
      microwave background anomalies, or of the late time dark energy. We show that,
      quite generally, the concrete realizations proposed so far are plagued by
      instabilities (either ghosts or unstable growth of the linearized perturbations)
      which can be ultimately related to the longitudinal vector polarization present
      in them. Phenomenological results based on these models are therefore unreliable.

PMID- 19392188
TI  - How to derotate the cosmic microwave background polarization.
AB  - If the linear polarization of the cosmic microwave background is rotated in a
      frequency-independent manner as it propagates from the surface of last scatter,
      it may introduce a B-mode polarization. Here I show that measurement of higher
      order TE, EE, EB, and TB correlations induced by this rotation can be used to
      reconstruct the rotation angle as a function of position on the sky. This
      technique can be used to distinguish primordial B modes from those induced by
      rotation. The effects of rotation can be distinguished geometrically from similar
      effects due to cosmic shear.

PMID- 19392189
TI  - Fractal properties of quantum spacetime.
AB  - We show that, in general, a spacetime having a quantum group symmetry has also a
      scale-dependent fractal dimension which deviates from its classical value at
      short scales, a phenomenon that resembles what is observed in some approaches to
      quantum gravity. In particular, we analyze the cases of a quantum sphere and of
      kappa-Minkowski spacetime, the latter being relevant in the context of quantum
      gravity.

PMID- 19392190
TI  - Deconfinement phase transition in N=4 super Yang-Mills theory on R x S3 from
      supersymmetric matrix quantum mechanics.
AB  - We test the recent claim that supersymmetric matrix quantum mechanics with mass
      deformation preserving maximal supersymmetry can be used to study N=4 super Yang
      Mills theory on R x S{3} in the planar limit. When the mass parameter is large,
      we can integrate out all of the massive fluctuations around a particular
      classical solution, which corresponds to R x S{3}. The resulting effective theory
      for the gauge field moduli at finite temperature reproduces the deconfinement
      phase transition in N=4 super Yang-Mills theory on R x S{3} at weak coupling.
      This transition was speculated to be a continuation of the conjectured phase
      transition at strong coupling, which corresponds to the Hawking-Page transition
      based on the gauge-gravity duality. At strong coupling, one can study the target
      theory by the new simulation method for supersymmetric matrix quantum mechanics.

PMID- 19392191
TI  - New approach to the micro--Bmicro problem of gauge-mediated supersymmetry
      breaking.
AB  - We present a new approach to the microBmicro problem of gauge-mediated
      supersymmetry breaking. Rather than reducing the generically large contribution
      to Bmicro we point out that acceptable electroweak symmetry breaking can be
      achieved with micro{2}<<Bmicro if at the same time Bmicro<<mH{d}}{2}. This
      hierarchy can easily appear in models where the Higgs fields are directly coupled
      to the supersymmetry breaking sector. Such models can yield novel electroweak
      symmetry breaking vacua, can deal with the supersymmetric flavor and CP problems,
      allow for gauge coupling unification, and result in distinct phenomenological
      predictions for the spectrum of superparticles.

PMID- 19392192
TI  - Threshold resummation for squark-antisquark and gluino-pair production at the
      LHC.
AB  - We study the effect of soft gluon emission in the hadroproduction of squark
      antisquark and gluino-gluino pairs at the next-to-leading logarithmic (NLL)
      accuracy within the framework of the minimal supersymmetric model. The one-loop
      soft anomalous dimension matrices controlling the color evolution of the
      underlying hard-scattering processes are calculated. We present the resummed
      total cross sections and show numerical results for proton-proton collisions at
      14 TeV. For the gluino-pair production, the theoretical uncertainty due to scale
      variation is reduced to the few-percent level.

PMID- 19392194
TI  - Discovery of 229Rn and the structure of the heaviest Rn and Ra isotopes from
      Penning-trap mass measurements.
AB  - The masses of the neutron-rich radon isotopes {223-229}Rn have been determined
      for the first time, using the ISOLTRAP setup at CERN ISOLDE. In addition, this
      experiment marks the first discovery of a new nuclide, 229Rn, by Penning-trap
      mass measurement. The new, high-accuracy data allow a fine examination of the
      mass surface, via the valence-nucleon interaction deltaV{pn}. The results reveal
      intriguing behavior, possibly reflecting either a N=134 subshell closure or an
      octupolar deformation in this region.

PMID- 19392197
TI  - Exact dynamical exchange-correlation kernel of a weakly inhomogeneous electron
      gas.
AB  - The dynamical exchange-correlation kernel f{xc} of a nonuniform electron gas is
      an essential input for the time-dependent density-functional theory of electronic
      systems. The long-wavelength behavior of this kernel is known to be of the form
      f{xc}=alpha/q{2} where q is the wave vector and alpha is a frequency-dependent
      coefficient. We show that in the limit of weak nonuniformity the coefficient
      alpha has a simple and exact expression in terms of the ground-state density and
      the frequency-dependent kernel of a uniform electron gas at the average density.
      We present an approximate evaluation of this expression for Si and discuss its
      implications for the theory of excitonic effects.

PMID- 19392195
TI  - Partial dynamical symmetry in quantum Hamiltonians with higher-order terms.
AB  - A generic procedure is proposed to construct many-body quantum Hamiltonians with
      partial dynamical symmetry. It is based on a tensor decomposition of the
      Hamiltonian and allows the construction of a hierarchy of interactions that have
      selected classes of solvable states. The method is illustrated in the SO(6) limit
      of the interacting boson model of atomic nuclei and applied to the nucleus 196Pt.

PMID- 19392196
TI  - Isospin dependence of incomplete fusion reactions at 25 MeV/nucleon.
AB  - 40Ca+;{40,48}Ca,46Ti reactions at 25 MeV/nucleon have been studied using the 4pi
      CHIMERA detector. An isospin effect on the competition between fusionlike and
      binarylike reaction mechanisms has been observed. The probability of producing a
      heavy residue is lower in the case of N approximately Z colliding systems as
      compared to the case of reactions induced on the neutron rich 48Ca target.
      Predictions based on constrained molecular dynamics II calculations show that the
      competition between fusionlike and binary reactions in the selected centrality
      bins can constrain the parametrization of the symmetry energy and its density
      dependence in the nuclear equation of state.

PMID- 19392186
TI  - All-sky LIGO search for periodic gravitational waves in the early fifth-science
      run data.
AB  - We report on an all-sky search with the LIGO detectors for periodic gravitational
      waves in the frequency range 50-1100 Hz and with the frequency's time derivative
      in the range -5 x 10{-9}-0 Hz s{-1}. Data from the first eight months of the
      fifth LIGO science run (S5) have been used in this search, which is based on a
      semicoherent method (PowerFlux) of summing strain power. Observing no evidence of
      periodic gravitational radiation, we report 95% confidence-level upper limits on
      radiation emitted by any unknown isolated rotating neutron stars within the
      search range. Strain limits below 10{-24} are obtained over a 200-Hz band, and
      the sensitivity improvement over previous searches increases the spatial volume
      sampled by an average factor of about 100 over the entire search band. For a
      neutron star with nominal equatorial ellipticity of 10{-6}, the search is
      sensitive to distances as great as 500 pc.

PMID- 19392198
TI  - Strong laser field fragmentation of H2: Coulomb explosion without double
      ionization.
AB  - We observe fragmentation of H2 molecules exposed to strong laser fields into
      excited neutral atoms. The measured excited neutral fragment spectrum resembles
      the ionic fragmentation spectrum including peaks due to bond softening and
      Coulomb explosion. To explain the occurrence of excited neutral fragments and
      their high kinetic energy, we argue that the recently investigated phenomenon of
      frustrated tunnel ionization is also at work in the neutralization of H+ ions
      into excited H atoms. In this process the tunneled electron does not gain enough
      drift energy from the laser field to escape the Coulomb potential and is
      recaptured. Calculation of classical trajectories as well as a correlated
      detection measurement of neutral excited H and H+ ions support the mechanism.

PMID- 19392199
TI  - Photonic micro-electromechanical systems vibrating at X-band (11-GHz) rates.
AB  - We report on an opto-mechanical resonator with vibration excited by compressive
      radiation pressure via stimulated Brillouin scattering [SBS]. We experimentally
      excite a mechanical whispering-gallery mode (WGM) from an optical WGM and detect
      vibration via the red Doppler shifted (Stokes) light it scatters. We numerically
      solve the stress-strain equation to calculate the circumferentially circulating
      mechanical WGM and reveal mechanical WGMs with a variety of transverse shapes.
      Frequency in our device is limited by the shortest optical wavelength it can
      transmit, irrespective of device size.

PMID- 19392200
TI  - Scattering forces from the curl of the spin angular momentum of a light field.
AB  - Light forces on small (Rayleigh) particles are usually described as the sum of
      two terms: the dipolar or gradient force and the scattering or radiation pressure
      force. The scattering force is traditionally considered proportional to the
      Poynting vector, which gives the direction and magnitude of the momentum flow.
      However, as we will show, there is an additional nonconservative contribution to
      the scattering force arising in a light field with nonuniform helicity. This
      force is shown to be proportional to the curl of the spin angular momentum of the
      light field. The relevance of the spin force is illustrated in the simple case of
      a 2D field geometry arising in the intersection region of two standing waves.

PMID- 19392201
TI  - Terahertz spectroscopy of plasmonic fractals.
AB  - We use terahertz time-domain spectroscopy to study the transmission properties of
      metallic films perforated with aperture arrays having deterministic or stochastic
      fractal morphologies ("plasmonic fractals"), and compare them with random
      aperture arrays. All of the measured plasmonic fractals show transmission
      resonances and antiresonances at frequencies that correspond to prominent
      features in their structure factors in k space. However, in sharp contrast to
      periodic aperture arrays, the resonant transmission enhancement decreases with
      increasing array size. This property is explained using a density-density
      correlation function, and is utilized for determining the underlying fractal
      dimensionality, D(<2). Furthermore, a sum rule for the transmission resonances
      and antiresonances in plasmonic fractals relative to the transmission of the
      corresponding random aperture arrays is obtained, and is shown to be universal.

PMID- 19392193
TI  - Observation of two-source interference in the photoproduction reaction AuAu -->
      AuAurho0.
AB  - In ultraperipheral relativistic heavy-ion collisions, a photon from the
      electromagnetic field of one nucleus can fluctuate to a quark-antiquark pair and
      scatter from the other nucleus, emerging as a rho{0}. The rho{0} production
      occurs in two well-separated (median impact parameters of 20 and 40 F for the
      cases considered here) nuclei, so the system forms a two-source interferometer.
      At low transverse momenta, the two amplitudes interfere destructively,
      suppressing rho{0} production. Since the rho{0} decays before the production
      amplitudes from the two sources can overlap, the two-pion system can only be
      described with an entangled nonlocal wave function, and is thus an example of the
      Einstein-Podolsky-Rosen paradox. We observe this suppression in 200 GeV per
      nucleon-pair gold-gold collisions. The interference is 87%+/-5%(stat.)+/
      8%(syst.) of the expected level. This translates into a limit on decoherence due
      to wave function collapse or other factors of 23% at the 90% confidence level.

PMID- 19392202
TI  - Metamaterials: optical activity without chirality.
AB  - We report that the classical phenomenon of optical activity, which is
      traditionally associated with chirality (helicity) of organic molecules,
      proteins, and inorganic structures, can be observed in artificial planar media
      which exhibit neither 3D nor 2D chirality. We observe the effect in the microwave
      and optical parts of the spectrum at oblique incidence to regular arrays of
      nonchiral subwavelength metamolecules in the form of strong circular dichroism
      and birefringence indistinguishable from those of chiral three-dimensional media.

PMID- 19392203
TI  - Hairpin vortex solution in planar couette flow: a tapestry of knotted vortices.
AB  - A numerical continuation method has been carried out seeking solutions for two
      distinct flow configurations, planar Couette flow (PCF) and laterally heated flow
      in a vertical slot (LHF). We found that the spanwise vortex solution in LHF
      identifies a new solution in PCF. The vortical structure of our new solution has
      the shape of a hairpin observed ubiquitously in high-Reynolds-number turbulent
      flow, and we believe this discovery may provide the paradigm for a hierarchical
      organization of coherent structures in turbulent shear layers.

PMID- 19392204
TI  - Statistical properties of directional ocean waves: the role of the modulational
      instability in the formation of extreme events.
AB  - We discuss two independent, large scale experiments performed in two wave basins
      of different dimensions in which the statistics of the surface wave elevation are
      addressed. Both facilities are equipped with a wave maker capable of generating
      waves with prescribed frequency and directional properties. The experimental
      results show that the probability of the formation of large amplitude waves
      strongly depends on the directional properties of the waves. Sea states
      characterized by long-crested and steep waves are more likely to be populated by
      freak waves with respect to those characterized by a large directional spreading.

PMID- 19392205
TI  - Coherent electron cooling.
AB  - Cooling intense high-energy hadron beams poses a major challenge for modern
      accelerator physics. The synchrotron radiation emitted from such beams is feeble;
      even in the Large Hadron Collider (LHC) operating with 7 TeV protons, the
      longitudinal damping time is about 13 hours. None of the traditional cooling
      methods seem able to cool LHC-class protons beams. In this Letter, we present a
      novel method of coherent electron cooling based on a high-gain free-electron
      laser (FEL). This technique could be critical for reaching high luminosities in
      hadron and electron-hadron colliders.

PMID- 19392207
TI  - Correlation between electron transport and shear Alfven activity in the National
      Spherical Torus Experiment.
AB  - We report the observation of a correlation between shear Alfven eigenmode
      activity and electron transport in plasma regimes where the electron temperature
      gradient is flat, and thus the drive for temperature gradient microinstabilities
      is absent. Plasmas having rapid central electron transport show intense,
      broadband global Alfven eigenmode (GAE) activity in the 0.5-1.1 MHz range, while
      plasmas with low transport are essentially GAE-free. The first theoretical
      assessment of a GAE-electron transport connection indicates that overlapping
      modes can resonantly couple to the bulk thermal electrons and induce their
      stochastic diffusion.

PMID- 19392206
TI  - X-ray Thomson-scattering measurements of density and temperature in shock
      compressed beryllium.
AB  - We present the first x-ray scattering measurements of the state of compression
      and heating in laser irradiated solid beryllium. The scattered spectra at two
      different angles show Compton and plasmon features indicating a dense Fermi
      degenerate plasma state with a Fermi energy above 30 eV and with temperatures in
      the range of 10-15 eV. These measurements indicate compression by a factor of 3
      in agreement with Hugoniot data and detailed radiation-hydrodynamic modeling.

PMID- 19392208
TI  - Magnetic reconnection in two-dimensional magnetohydrodynamic turbulence.
AB  - Systematic analysis of numerical simulations of two-dimensional
      magnetohydrodynamic turbulence reveals the presence of a large number of X-type
      neutral points where magnetic reconnection occurs. We examine the statistical
      properties of this ensemble of reconnection events that are spontaneously
      generated by turbulence. The associated reconnection rates are distributed over a
      wide range of values and scales with the geometry of the diffusion region.
      Locally, these events can be described through a variant of the Sweet-Parker
      model, in which the parameters are externally controlled by turbulence. This new
      perspective on reconnection is relevant in space and astrophysical contexts,
      where plasma is generally in a fully turbulent regime.

PMID- 19392209
TI  - Demonstration of effective control of fast-ion-stabilized sawteeth by electron
      cyclotron current drive.
AB  - In a tokamak plasma, sawtooth oscillations in the central temperature, caused by
      a magnetohydrodynamic instability, can be partially stabilized by fast ions. The
      resulting less frequent sawtooth crashes can trigger unwanted magnetohydrodynamic
      activity. This Letter reports on experiments showing that modest electron
      cyclotron current drive power, with the deposition positioned by feedback control
      of the injection angle, can reliably shorten the sawtooth period in the presence
      of ions with energies >or=0.5 MeV. Certain surprising elements of the results are
      evaluated qualitatively in terms of existing theory.

PMID- 19392210
TI  - Residual-current excitation in plasmas produced by few-cycle laser pulses.
AB  - Along with the generation of extreme-ultraviolet and soft x-ray radiation, gas
      ionization by an intense few-cycle laser pulse can also induce the generation of
      low-frequency terahertz waves. The latter is caused by the excitation of a
      residual quasi-dc current in the produced plasma by the electric field of the
      laser pulse. We describe this phenomenon using the quantum-mechanical approach
      based on solving the 3D time-dependent Schrodinger equation. We calculate the
      dependences of the residual-current density on the carrier-envelope phase,
      duration, and intensity of the few-cycle laser pulse, and find optimal conditions
      for high-efficiency realization of the studied phenomenon.

PMID- 19392211
TI  - Positive ion induced solidification of 4He.
AB  - We have observed bulk solidification of 4He induced by nucleation on positive
      alkali ions in pressurized superfluid helium. The ions are extracted into the
      liquid from alkali-doped solid He by a static electric field. The experiments
      prove the existence of charged particles in a solid structure composed of doped
      He that was recently shown to coexist with superfluid helium below the He
      solidification pressure. This supports our earlier suggestion that the Coulomb
      interaction of positive ions surrounded by a solid He shell (snowballs) and
      electrons trapped in spherical cavities (electron bubbles), together with surface
      tension, is responsible for the stability of that structure against melting. We
      have determined the density of charges in the sample by two independent methods.

PMID- 19392212
TI  - Mechanism of the band gap opening across the order-disorder transition of
      Si(111)(4 x 1)-In.
AB  - The ground state properties of indium atom chains on the Si(111) 8 x 2-In surface
      and the nature of their insulator-metal (IM) transition near 120 K are under
      intense dispute. We compare experimental scanning tunneling microscopy (STM)
      images of the low temperature (LT) 8 x 2 phase with STM image calculations from
      Density Functional Theory (DFT). Our LT studies clearly indicate the existence of
      a frozen shear distortion between neighboring atom chains, resulting in the
      formation of indium hexagons. Tunneling spectra furthermore indicate that the IM
      transition coincides with the collapse of a approximately 0.3 eV surface-state
      band gap at the Gamma point of the 4 x 2 Brillouin zone. This implies that the IM
      transition is driven by a shear phonon, not by Fermi surface nesting.

PMID- 19392213
TI  - Slip line growth as a critical phenomenon.
AB  - We study the growth of a slip line in a plastically deforming crystal by
      numerical simulation of a double-ended pileup model with a dislocation source at
      one end, and an absorbing wall at the other end. In the presence of defects, the
      pileup undergoes a continuous nonequilibrium phase transition as a function of
      stress, which can be characterized by finite-size scaling. We obtain a complete
      set of critical exponents and scaling functions that describe the spatiotemporal
      dynamics of the slip line. Our findings allow us to reinterpret earlier
      experiments on slip line kinematography as evidence of a dynamic critical
      phenomenon.

PMID- 19392214
TI  - Structures of insulating phases of dense lithium.
AB  - Two high-pressure insulating phases of lithium were predicted using random search
      and evolutionary algorithm methods with first-principles electronic structure
      calculations. It is shown that lithium will transform from the metallic cubic
      cI16 phase to an insulating monoclinic C2 structure at 74 GPa. The C2 structure
      is the most stable phase up to 91 GPa, where it transforms to a second insulating
      orthorhombic Aba2 structure. The C2 and Aba2 structures are the first theoretical
      models explicitly showing the band gap opening in compressed lithium. The
      theoretical findings are supported by recent experimental evidence from
      electrical resistance and x-ray diffraction measurements.

PMID- 19392215
TI  - Demixing of hydrogen and helium at megabar pressures.
AB  - We present results of ab initio finite-temperature density functional theory
      molecular dynamics simulations for fluid hydrogen-helium mixtures at megabar
      pressures. The location of the miscibility gap is derived from the equation of
      state data. We find a close relation between hydrogen-helium phase separation and
      the continuous nonmetal-to-metal transition in hydrogen. Our calculations predict
      that demixing of hydrogen and helium occurs in Saturn and probably also in
      Jupiter. These results will have a strong impact on interior models of giant
      solar and extrasolar planets.

PMID- 19392216
TI  - Nanoscale brushes: how to build a smart surface coating.
AB  - Via computer simulations, we demonstrate how a densely grafted layer of polymers,
      a brush, could be turned into an efficient switch through chemical modification
      of some of its end monomers. In this way, a surface coating with reversibly
      switchable properties can be constructed. We analyze the fundamental physical
      principle behind its function, a recently discovered surface instability, and
      demonstrate that the combination of a high grafting density, an inflated end
      group size, and a high degree of monodispersity is a condition for an optimal
      functionality of the switch.

PMID- 19392217
TI  - Viscosity behavior spanning four orders of magnitude in As-S melts under high
      pressure.
AB  - Under compression, the As-S liquids are subject to transformations, including
      polymerization and metallization. We have measured the viscosity of the As-S
      liquids under high pressures. As a result, large viscosity variations by 4-5
      orders of magnitude have been revealed. The viscosity values of the As-S liquids
      are moderate in the molecular state, very high in the covalent state, and low in
      the metallic state. Therefore, predicting the viscosity behavior in other melts
      under pressure is possible, which is of considerable importance for the physics
      of glass transition, geophysics, and material science.

PMID- 19392218
TI  - Atomic structure of the epitaxial BaO/Si(001) interface.
AB  - We present the structure of the interface responsible for epitaxy of crystalline
      oxides on silicon. Using synchrotron x-ray diffraction, we observe a 2 x 1 unit
      cell reconstruction at the interface of BaO grown on Si(001) terminated with 1/2
      ML of Sr. Since this symmetry is not present in bulk BaO or Si, only the
      interface contributes to diffracted intensity. First principles calculations
      accurately predict the observed diffraction and identify the structure of the
      BaO/Si interface, including the elemental composition and a sub-A rumpling due to
      epitaxial strain of the 7 adjacent BaO and Si layers.

PMID- 19392219
TI  - Spin blockade, orbital occupation, and charge ordering in La1.5Sr0.5CoO4.
AB  - Using Co-L2,3 and O-K x-ray absorption spectroscopy, we reveal that the charge
      ordering in La1.5Sr0.5CoO4 involves high spin (S=3/2) Co2+ and low spin (S=0)
      Co3+ ions. This provides evidence for the spin-blockade phenomenon as a source
      for the extremely insulating nature of the La2-xSrxCoO4 series. The associated
      e{g}{2} and e{g}{0} orbital occupation accounts for the large contrast in the Co
      O bond lengths and, in turn, the high charge ordering temperature. Yet, the low
      magnetic ordering temperature is naturally explained by the presence of the
      nonmagnetic (S=0) Co3+ ions. From the identification of the bands we infer that
      La1.5Sr0.5CoO4 is a narrow band material.

PMID- 19392220
TI  - Conductance of fully equilibrated quantum wires.
AB  - We study the conductance of a quantum wire in the presence of weak electron
      electron scattering. In a sufficiently long wire the scattering leads to full
      equilibration of the electron distribution function in the frame moving with the
      electric current. At nonzero temperature this equilibrium distribution differs
      from the one supplied by the leads. As a result the contact resistance increases,
      and the quantized conductance of the wire acquires a quadratic in temperature
      correction. The magnitude of the correction is found by analysis of the
      conservation laws of the system and does not depend on the details of the
      interaction mechanism responsible for equilibration.

PMID- 19392221
TI  - Nuclear magnetism and electronic order in 13C nanotubes.
AB  - Single wall carbon nanotubes grown entirely from 13C form an ideal system to
      study the effect of electron interaction on nuclear magnetism in one dimension.
      If the electrons are in the metallic, Luttinger liquid regime, we show that even
      a very weak hyperfine coupling to the 13C nuclear spins has a striking effect:
      The system is driven into an ordered phase, which combines electron and nuclear
      degrees of freedom, and which persists up into the millikelvin range. In this
      phase the conductance is reduced by a universal factor of 2, allowing for
      detection by standard transport experiments.

PMID- 19392222
TI  - Self-masking of spontaneous symmetry breaking in layer materials.
AB  - We study d-wave Fermi-surface deformations (dFSD), the so-called Pomeranchuk
      instability, on bilayer and infinite-layer square lattices. Since the order
      parameter of the dFSD has Ising symmetry, there are two stacking patterns along
      the c axis: (+, +) and (+, -). We find that, as long as the c axis dispersion is
      finite at the saddle points of the in-plane band dispersion, the (+, -) stacking
      is usually favored independently on the details of interlayer coupling, yielding
      no macroscopic anisotropy. The dFSD provides unique spontaneous symmetry breaking
      that is self-masked in layer materials.

PMID- 19392223
TI  - Direct measurement of the percolation probability in carbon nanofiber-polyimide
      nanocomposites.
AB  - We present the first experimental measurement of the geometric critical exponent
      beta associated with the percolation probability, the probability a metallic
      filler belongs to the conducting network, of an electrical composite. The
      technique employs conducting-tip atomic force microscopy to obtain a conducting
      areal density, and is demonstrated on polyimide nanocomposites containing
      different concentrations of carbon nanofibers. We find beta approximately 1 and t
      (the exponent for bulk conductivity) approximately 3. These values are consistent
      with the predictions for the Bethe lattice and larger than the values predicted
      in the 3D lattice percolation model. Hence, this electrical composite likely
      belongs to the same universality class as the Bethe lattice. The ability to
      measure geometric and transport critical exponents on the same material is
      critical to drawing this conclusion.

PMID- 19392224
TI  - Charge transport in semiconductors with multiscale conformational dynamics.
AB  - In partially ordered organic semiconductors, the characteristic times of nuclear
      motion are comparable to those of charge carrier dynamics. It is impossible to
      describe charge transport using either static disorder models or temperature
      averaged electronic Hamiltonians. We build a model Hamiltonian which allows the
      study of charge transport whenever carrier and nuclear dynamics are not easily
      separable. Performing nanoseconds long molecular dynamics of a columnar mesophase
      of a discotic liquid crystal and evaluating electronic couplings, we identify
      realistic parameters of the Hamiltonian. All modes which are coupled to the
      electron dynamics can be described in the model Hamiltonian by a limited number
      of Langevin oscillators. This method can be applied to systems with both slow
      (nanoseconds) and fast (hundreds of femtoseconds) nuclear motions, i.e., with
      both dynamic and static disorder.

PMID- 19392225
TI  - Testing the topological nature of the fractional quantum Hall edge.
AB  - We carry out numerical diagonalization for much larger systems than before by
      restricting the fractional quantum Hall (FQH) edge excitations to a basis that is
      exact for a short-range interaction and very accurate for the Coulomb
      interaction. This enables us to perform substantial tests of the predicted
      universality of the edge physics. Our results suggest the possibility that the
      behavior of the FQH edge is intrinsically nonuniversal, even in the absence of
      edge reconstruction, and therefore may not bear a sharp and unique relation to
      the nature of the bulk FQH state.

PMID- 19392226
TI  - Electrical generation of pure spin currents in a two-dimensional electron gas.
AB  - Pure spin currents are generated and detected in micron-wide channels of a GaAs
      two-dimensional electron gas, using quantum point contacts in an in-plane
      magnetic field as injectors and detectors. The enhanced sensitivity to spin
      transport offered by a nonlocal measurement geometry enables accurate spin
      current measurements in this widely studied physical system. The polarization of
      the contacts is used to extract the quantum point contact g factor and provides a
      test for spontaneous polarization at 0.7 structure. The spin relaxation length in
      the channel is 30-50 microm over the magnetic field range 3-10 T, much longer
      than has been reported in GaAs two-dimensional electron gases but shorter than
      that expected from Dyakonov-Perel relaxation.

PMID- 19392227
TI  - Pathway for the transformation from highly oriented pyrolytic graphite into
      amorphous diamond.
AB  - We report the discovery of a novel pathway for the transformation from highly
      oriented pyrolytic graphite foils into amorphous diamond platelets. This pathway
      consists of three stages of neutron irradiation, shock compression, and rapid
      quenching. We obtained transparent platelets which show photoluminescence but no
      diamond Raman peak, similar to the case of amorphous diamond synthesized from C60
      fullerene. Wigner defects formed by irradiation are considered to make a high
      density of diamond nucleation sites under shock compression, of which growth is
      suppressed by rapid quenching.

PMID- 19392228
TI  - Type-1.5 superconductivity.
AB  - We demonstrate the existence of a novel superconducting state in high quality two
      component MgB2 single crystalline superconductors where a unique combination of
      both type-1 (lambda{1}/xi{1}<1/sqrt[2]) and type-2 (lambda{2}/xi{2}>1/sqrt[2])
      superconductor conditions is realized for the two components of the order
      parameter. This condition leads to a vortex-vortex interaction attractive at long
      distances and repulsive at short distances, which stabilizes unconventional
      stripe- and gossamerlike vortex patterns that we have visualized in this type-1.5
      superconductor using Bitter decoration and also reproduced in numerical
      simulations.

PMID- 19392229
TI  - Distinct pseudogap and quasiparticle relaxation dynamics in the superconducting
      state of nearly optimally doped SmFeAsO0.8F0.2 single crystals.
AB  - We use femtosecond spectroscopy to investigate the quasiparticle relaxation and
      low-energy electronic structure in a nearly optimally doped pnictide
      superconductor with T{c}=49.5 K. Multiple relaxation processes are evident, with
      distinct superconducting state quasiparticle recombination dynamics exhibiting a
      T-dependent superconducting gap, and a clear "pseudogaplike" feature with an
      onset above 180 K indicating the existence of a temperature-independent gap of
      magnitude Delta{PG}=61+/-9 meV above T{c}. Both the superconducting and pseudogap
      components show saturation as a function of fluence with distinct saturation
      fluences 4 and 40 microJ/cm{2}, respectively.

PMID- 19392230
TI  - Model for vortex-core tunneling spectroscopy of chiral p-wave superconductors via
      odd-frequency pairing states.
AB  - The local density of states is studied theoretically in terms of the odd
      frequency (odd-omega) Cooper pairing induced around a vortex core. We find that a
      zero energy peak in the density of states at the vortex center is robust against
      nonmagnetic impurities in a chiral p-wave superconductor owing to an odd-omega s
      wave pair amplitude. We suggest how to discriminate a spin-triplet pairing
      symmetry and spatial chiral-domain structure by scanning tunneling spectroscopy
      via odd-omega pair amplitudes inside vortex cores.

PMID- 19392231
TI  - Pseudoisotropic upper critical field in cobalt-doped SrFe2As2 epitaxial films.
AB  - We present resistivity measurements of the complete superconducting upper
      critical field (H{c2}) phase diagram as a function of angle (theta) and
      temperature (T) for cobalt-doped SrFe2As2 epitaxial films to 0.5 K and 50 T.
      Although H{c2}(theta) at 10 K is indistinguishable from that derived from a
      single-band anisotropy model, the apparent anisotropy H{c2}{
      perpendicularc}/H{c2};{ parallelc} linearly decreases to 1 at low T, with
      H{c2}(0)=47 T. The data are well described by a two-band model with small,
      opposing anisotropies for the bands. This unusual relationship is confirmed by
      the observation of a local maximum for H{c2};{ parallelc} at low T.

PMID- 19392232
TI  - Anisotropy in the electrical resistivity and susceptibility of superconducting
      BaFe2As2 single crystals.
AB  - We report that sizable single crystals of BaFe2As2 have been grown with the self
      flux method. Measurements and anisotropy of intrinsic transport and magnetic
      properties from high-quality single crystal are first presented. The resistivity
      anisotropy (rho{c}/rho{ab}) is as large as 150 and independent of temperature. In
      contrast to the susceptibility behavior observed in polycrystalline samples, no
      Curie-Weiss behavior is observed, and a linear-T dependent susceptibility occurs
      from the spin-density-wave transition temperature, (T{s}), to 700 K. This result
      suggests that strong antiferromagnetic correlations are present well above T{s}.
      A twofold symmetry of susceptibility in the ab plane indicates a stripelike spin
      structure as observed by neutron scattering. The resistivity minimum is strongly
      dependent on the magnetic field, suggesting that the upturn of the resistivity at
      low temperatures should be related to spin fluctuation.

PMID- 19392233
TI  - Electronic phase separation in the slightly underdoped iron pnictide
      superconductor Ba1-xKxFe2As2.
AB  - Here we present a combined study of the slightly underdoped novel pnictide
      superconductor Ba1-xKxFe2As2 by means of x-ray powder diffraction, neutron
      scattering, muon-spin rotation (microSR), and magnetic force microscopy (MFM).
      Static antiferromagnetic order sets in below T{m} approximately 70 K as inferred
      from the neutron scattering and zero-field-microSR data. Transverse-field microSR
      below Tc shows a coexistence of magnetically ordered and nonmagnetic states,
      which is also confirmed by MFM imaging. We explain such coexistence by electronic
      phase separation into antiferromagnetic and superconducting- or normal-state
      regions on a lateral scale of several tens of nanometers. Our findings indicate
      that such mesoscopic phase separation can be considered an intrinsic property of
      some iron pnictide superconductors.

PMID- 19392234
TI  - Evidence for time-reversal symmetry breaking in the noncentrosymmetric
      superconductor LaNiC2.
AB  - Muon spin relaxation experiments on the noncentrosymmetric intermetallic
      superconductor LaNiC2 are reported. We find that the onset of superconductivity
      coincides with the appearance of spontaneous magnetic fields, implying that in
      the superconducting state time-reversal symmetry is broken. An analysis of the
      possible pairing symmetries suggests only four triplet states compatible with
      this observation, all of them nonunitary. They include the intriguing possibility
      of triplet pairing with the full point group symmetry of the crystal, which is
      possible only in a noncentrosymmetric superconductor.

PMID- 19392235
TI  - Laser-induced magnetization dynamics of lanthanide-doped permalloy thin films.
AB  - We investigate the effect of Ho, Dy, Tb, and Gd impurities on the femtosecond
      laser-induced magnetization dynamics of thin Permalloy films using the time
      resolved magneto-optical Kerr effect. Varying the amount of Ho, Dy, Tb content
      from 0% to 8%, we observe a gradual change of the characteristic demagnetization
      time constant from approximately 60 to approximately 150 fs. In contrast, Gd
      concentrations up to 15% do not influence the time scale of the initial
      photoinduced magnetization loss. We propose a demagnetization mechanism that
      relies on strong magnetic inertia of the rare-earth dopant which stabilizes the
      ferrimagnetic ordering and thereby delays the demagnetization.

PMID- 19392236
TI  - Effect of a single dislocation in a heterostructure layer on the local
      polarization of a ferroelectric layer.
AB  - We study, on an atomic scale, the influence of a single dislocation in a SrTiO3
      sublayer on the local ferroelectric polarization of the neighboring ferroelectric
      PbZr0.2Ti0.8O3 (PZT) sublayer in an epitaxial SrTiO3/PbZr0.2Ti0.8O3/SrTiO3 three
      layer heterostructure. The strain field of the dislocation in the SrTiO3 layer
      propagates across the interface into the PZT layer and leads to a strong
      variation of the c-lattice parameter of the PZT layer. Accompanying a strong
      reduction of the c-lattice parameter, the off-center displacements of the Zr/Ti
      atoms away from the center of the oxygen octahedra are also strongly decreased,
      resulting in a decrease of the local spontaneous polarization by up to 48%.

PMID- 19392237
TI  - Engineering multiferroism in CaMnO3.
AB  - Structural instabilities of CaMnO3 are investigated from first principles. We
      point out that, on top of a strong antiferrodistortive instability responsible
      for its orthorhombic ground state, the cubic perovskite structure of CaMnO3 also
      exhibits a weak ferroelectric instability. Although ferroelectricity is
      suppressed by antiferrodistortive motions, we show that it can be favored using
      strain or chemical engineering in order to make CaMnO3 multiferroic. We finally
      highlight that the ferroelectric instability of CaMnO3 is Mn-dominated. This
      illustrates that, contrary to common belief, ferroelectricity and magnetism are
      not necessarily exclusive but can be driven by the same cation.

PMID- 19392238
TI  - Relaxation kinetics of nanoscale indents in a polymer glass.
AB  - Nanometer scale indents have been written in a cross-linked polystyrene sample,
      and their relaxation has been studied at annealing temperatures well below the
      glass transition of the polymer. The indents represent a highly nonequilibrium
      state of the polymer which is subjected to mechanical stress of up to 0.4 GPa and
      thermal quench rates on the order of 10{8} K/s during writing. It is shown that
      the relaxation towards equilibrium evolves logarithmically over more than 10
      orders of magnitude in time. The relaxation kinetics are accurately described in
      terms of a thermally activated process with an energy barrier whose magnitude
      decreases linearly with the distance from equilibrium.

PMID- 19392239
TI  - Crowding effects on the structural transitions in a flexible helical homopolymer.
AB  - We elucidate the structural transitions in a helical off-lattice homopolymer
      induced by crowding agents, as a function of the number of monomers (N) and
      volume fraction (varphi c) of crowding particles. At varphic=0, the homopolymer
      undergoes transitions from a random coil to a helix, helical hairpin HH, and
      helix bundle HB structures depending on N, and temperature. Crowding induces
      chain compaction that can promote HH or HB formation depending on varphic.
      Typically, the helical content decreases which is reflected in the decrease in
      the transition temperatures that depend on varphic, N, and the size of the
      crowding particles.

PMID- 19392241
TI  - Self-assembled magnetic surface swimmers.
AB  - We report studies of novel self-assembled magnetic surface swimmers (magnetic
      snakes) formed from a dispersion of magnetic microparticles at a liquid-air
      interface and energized by an alternating magnetic field. We show that under
      certain conditions the snakes spontaneously break the symmetry of surface flows
      and turn into self-propelled objects. Parameters of the driving magnetic field
      tune the propulsion velocity of these snakelike swimmers. We find that the
      symmetry of the surface flows can also be broken in a controlled fashion by
      attaching a large bead to a magnetic snake (bead-snake hybrid), transforming it
      into a self-locomoting entity. The observed phenomena have been successfully
      described by a phenomenological model based on the amplitude equation for surface
      waves coupled to a large-scale hydrodynamic mean flow equation.

PMID- 19392240
TI  - Critical buckling length versus persistence length: what governs biofilament
      conformation?
AB  - We numerically study the length dependence in the bending stiffness of alpha
      helices, coiled coils, and a linear chain model. As the length approaches what we
      named the critical buckling length lc, the chain appears to become increasingly
      more flexible. This is due to weak nonbonded attractions that eventually lead to
      buckling instability and alter the chain's conformational ensemble. For alpha
      helices and coiled coils, lc is much less than their respective persistence
      lengths, so lc is the defining length scale for their conformations. These
      results elucidate the importance of weak nonspecific attractions that are
      inherent in many biofilaments in physiological conditions.

PMID- 19392242
TI  - Self-organization and cooperativity of weakly coupled molecular motors under
      unequal loading.
AB  - We study the collective dynamics of Brownian motors moving on a one-dimensional
      track when an external load is applied to the leading motor. Motors are driven by
      a two-state ratchet mechanism, which is appropriate to single-headed kinesins,
      and their relative motion is only constrained by their mutual interaction
      potential (weak coupling). We show that unequal loading enhances cooperativity,
      leading to the formation of clusters with velocities and efficiencies higher than
      those predicted by simple superposition. When a weak attraction between motors is
      present, we find nonmonotonic collective velocity-force curves, hysteretic
      phenomena, and a dynamic self-regulation mechanism that selects the cluster size
      for optimal performance.

PMID- 19392243
TI  - Phase diagram of single vesicle dynamical states in shear flow.
AB  - We report the first experimental phase diagram of vesicle dynamical states in a
      shear flow presented in a space of two dimensionless parameters suggested
      recently by V. Lebedev et al. To reduce errors in the control parameters, 3D
      geometrical reconstruction and determination of the viscosity contrast of a
      vesicle in situ in a plane Couette flow device prior to the experiment are
      developed. Our results are in accord with the theory predicting three distinctly
      separating regions of vesicle dynamical states in the plane of just two self
      similar parameters.

PMID- 19392244
TI  - Self-assembly and evolution of homomeric protein complexes.
AB  - We introduce a simple "patchy particle" model to study the thermodynamics and
      dynamics of self-assembly of homomeric protein complexes. Our calculations allow
      us to rationalize recent results for dihedral complexes. Namely, why evolution of
      such complexes naturally takes the system into a region of interaction space
      where (i) the evolutionarily newer interactions are weaker, (ii) subcomplexes
      involving the stronger interactions are observed to be thermodynamically stable
      on destabilization of the protein-protein interactions, and (iii) the self
      assembly dynamics are hierarchical with these same subcomplexes acting as kinetic
      intermediates.

PMID- 19392245
TI  - Instabilities and waves in thin films of living fluids.
AB  - We formulate the thin-film hydrodynamics of a suspension of polar self-driven
      particles and show that it is prone to several instabilities through the
      interplay of activity, polarity, and the existence of a free surface. Our
      approach extends, to self-propelling systems, the work of Ben Amar and Cummings
      [Phys. Fluids 13 1160 (2001)10.1063/1.1359748] on thin-film nematics. Based on
      our estimates the instabilities should be seen in bacterial suspensions and the
      lamellipodium, and are potentially relevant to the morphology of biofilms. We
      suggest several experimental tests of our theory.

PMID- 19392246
TI  - In silico relationship between configurational entropy and soft degrees of
      freedom in proteins and peptides.
AB  - Configurational entropies from temperature-dependent free energy calculations of
      proteins and peptides are compared with entropies determined as the sum of the
      Shannon entropies of a kernel density estimate of the dihedral angle probability
      distributions. We find that the entropy changes can be separated into independent
      contributions from hard and soft degrees of freedom. Furthermore, because the
      effects of motional correlations between dihedral angles on entropy differences
      are small, the functional role of configurational entropy changes can be
      interpreted in a spatially resolved manner.

PMID- 19392247
TI  - Nonequilibrium phase transitions in the extraction of membrane tubes by molecular
      motors.
AB  - The extraction of membrane tubes by molecular motors is known to play an
      important role for the transport properties of eukaryotic cells. By studying a
      generic class of models for the tube extraction, we discover a rich phase
      diagram. In particular we show that the density of motors along the tube can
      exhibit shocks, inverse shocks, and plateaux, depending on parameters which could
      in principle be probed experimentally. In addition the phase diagram exhibits
      interesting reentrant behavior.

PMID- 19392248
TI  - Phase transitions towards criticality in a neural system with adaptive
      interactions.
AB  - We analytically describe a transition scenario to self-organized criticality
      (SOC) that is new for physics as well as neuroscience; it combines the
      criticality of first and second-order phase transitions with a SOC phase. We
      consider a network of pulse-coupled neurons interacting via dynamical synapses,
      which exhibit depression and facilitation as found in experiments. We
      analytically show the coexistence of a SOC phase and a subcritical phase
      connected by a cusp bifurcation. Switching between the two phases can be
      triggered by varying the intensity of noisy inputs.

PMID- 19392249
TI  - Classical simulation of quantum energy flow in biomolecules.
AB  - Based on a comparison of classical and quantum-mechanical perturbation theory,
      the validity of classical nonequilibrium molecular dynamics simulations to
      describe vibrational energy redistribution in biomolecules is studied. Adopting a
      small model peptide in aqueous solution as an example, the theory correctly
      predicts quantum correction factors that need to be applied to the results of
      classical simulations in order to match the correct quantum results.

PMID- 19392250
TI  - Direct measurements of hydrophobic slippage using double-focus fluorescence cross
      correlation.
AB  - We report the results of direct measurements of velocity profiles in a
      microchannel with hydrophobic and hydrophilic walls, using a new high-precision
      method of double-focus spatial fluorescence cross correlation under a confocal
      microscope. In the vicinity of both walls the measured velocity profiles do not
      go to zero by supplying a plateau of constant velocity. This apparent slip is
      proven to be due to a Taylor dispersion, an augmentation by shear diffusion of
      nanotracers in the direction of flow. Comparing the velocity profiles near the
      hydrophobic and hydrophilic walls for various conditions shows that there is a
      true slip length due to hydrophobicity. This length, of the order of several tens
      of nanometers, is independent of the electrolyte concentration and shear rate.

PMID- 19392251
TI  - Correlation between cosmic rays and ozone depletion.
AB  - This Letter reports reliable satellite data in the period of 1980-2007 covering
      two full 11-yr cosmic ray (CR) cycles, clearly showing the correlation between
      CRs and ozone depletion, especially the polar ozone loss (hole) over Antarctica.
      The results provide strong evidence of the physical mechanism that the CR-driven
      electron-induced reaction of halogenated molecules plays the dominant role in
      causing the ozone hole. Moreover, this mechanism predicts one of the severest
      ozone losses in 2008-2009 and probably another large hole around 2019-2020,
      according to the 11-yr CR cycle.

PMID- 19392252
TI  - Comment on "nonmonotonicity in the quantum-classical transition: chaos induced by
      quantum effects".

PMID- 19392254
TI  - Comment on "intense nonlinear magnetic dipole radiation at optical frequencies:
      molecular scattering in a dielectric liquid".

PMID- 19392256
TI  - Distilling nonlocality.
AB  - Two parts of an entangled quantum state can have a correlation, in their joint
      behavior under measurements, that is unexplainable by shared classical
      information. Such correlations are called nonlocal and have proven to be an
      interesting resource for information processing. Since nonlocal correlations are
      more useful if they are stronger, it is natural to ask whether weak nonlocality
      can be amplified. We give an affirmative answer by presenting the first protocol
      for distilling nonlocality in the framework of generalized nonsignaling theories.
      Our protocol works for both quantum and nonquantum correlations. This shows that
      in many contexts, the extent to which a single instance of a correlation can
      violate a Clauser-Horne-Shimony-Holt inequality is not a good measure for the
      usefulness of nonlocality. A more meaningful measure follows from our results.

PMID- 19392257
TI  - Topological quantum computation via the quantum tunneling effect.
AB  - Quantum computers are predicted to utilize quantum states to process tasks far
      faster than those of conventional classical computers. In this Letter we show an
      alternative approach towards building topological quantum computers by tuning the
      quantum tunneling effect of degenerate quantum states in topological order,
      instead of braiding anyons. Using a designer Hamiltonian-the Wen-Plaquette model
      as an example, we study its quantum tunneling effect of the toric codes and show
      how to control the toric codes to realize topological quantum computation. In
      particular, we give a proposal to the measurement of the toric codes from
      Aharonov-Bohm interferences of quasiparticles.

PMID- 19392258
TI  - No-go theorem for gaussian quantum error correction.
AB  - We prove that Gaussian operations are of no use for protecting Gaussian states
      against Gaussian errors in quantum communication protocols. Specifically, we
      introduce a new quantity characterizing any single-mode Gaussian channel, called
      entanglement degradation, and show that it cannot decrease via Gaussian encoding
      and decoding operations only. The strength of this no-go theorem is illustrated
      with some examples of Gaussian channels.

PMID- 19392259
TI  - Concatenated control sequences based on optimized dynamic decoupling.
AB  - Two recent developments in quantum control, concatenation and optimization of
      pulse intervals, are combined to yield a strategy to suppress unwanted couplings
      in quantum systems to high order. Longitudinal relaxation and transverse
      dephasing can be suppressed so that systems with a small splitting between their
      energy levels can be kept isolated from their environment. The required number of
      pulses grows exponentially with the desired order but is only the square root of
      the number needed if only concatenation is used. An approximate scheme even
      brings the number down to polynomial growth. The approach is expected to be
      useful for quantum information and for high-precision nuclear magnetic resonance.

PMID- 19392260
TI  - Spectral function and quasiparticle damping of interacting Bosons in two
      dimensions.
AB  - We employ the functional renormalization group to study dynamical properties of
      the two-dimensional Bose gas. Our approach is free of infrared divergences, which
      plague the usual diagrammatic approaches, and is consistent with the exact
      Nepomnyashchy identity, which states that the anomalous self-energy vanishes at
      zero frequency and momentum. We recover the correct infrared behavior of the
      propagators and present explicit results for the spectral line shape, from which
      we extract the quasiparticle dispersion and damping.

PMID- 19392261
TI  - Asymptotic behavior of self-affine processes in semi-infinite domains.
AB  - We propose to model the stochastic dynamics of a polymer passing through a pore
      (translocation) by means of a fractional Brownian motion and study its behavior
      in the presence of an absorbing boundary. Based on scaling arguments and
      numerical simulations, we present a conjecture that provides a link between the
      persistence exponent theta and the Hurst exponent H of the process, thus shedding
      light on the spatial and temporal features of translocation. Furthermore, we show
      that this conjecture applies more generally to a broad class of self-affine
      processes undergoing anomalous diffusion in bounded domains, and we discuss some
      significant examples.

PMID- 19392262
TI  - Micromagic clock: microwave clock based on atoms in an engineered optical
      lattice.
AB  - We propose a new class of atomic microwave clocks based on the hyperfine
      transitions in the ground state of aluminum or gallium atoms trapped in optical
      lattices. For such elements magic wavelengths exist at which both levels of the
      hyperfine doublet are shifted at the same rate by the lattice laser field,
      cancelling its effect on the clock transition. A similar mechanism for the magic
      wavelengths may work in microwave hyperfine transitions in other atoms which have
      the fine-structure multiplets in the ground state.

PMID- 19392263
TI  - A natural framework for chaotic inflation.
AB  - We show that inflation with a quadratic potential occurs naturally in theories
      where an axionlike field mixes with a 4-form. Such an axion is massive, with the
      mass which arises from the mixing being protected by the axion shift symmetry.
      The 4-form backgrounds break this symmetry spontaneously and comprise a
      minilandscape, where their fluxes can change by emission of membranes. Inflation
      can begin when the 4-form dominates the energy density. Eventually, this energy
      is reduced by membrane emission, and the axion can roll slowly towards its
      minimum, as in the simplest version of chaotic inflation.

PMID- 19392264
TI  - Bulk viscosity and the conformal anomaly in the pion gas.
AB  - We calculate the bulk viscosity of the massive pion gas within unitarized chiral
      perturbation theory. We obtain a low-temperature peak arising from explicit
      conformal breaking due to the pion mass and another peak near the critical
      temperature, dominated by the conformal anomaly through gluon condensate terms.
      The correlation between bulk viscosity and conformal breaking supports a recent
      QCD proposal. We discuss the role of resonances, heavier states, and large-N_(c)
      counting.

PMID- 19392265
TI  - Large hierarchies from approximate R symmetries.
AB  - We show that hierarchically small vacuum expectation values of the superpotential
      in supersymmetric theories can be a consequence of an approximate R symmetry. We
      briefly discuss the role of such small constants in moduli stabilization and
      understanding the huge hierarchy between the Planck and electroweak scales.

PMID- 19392267
TI  - Naturalness of CP violation in the standard model.
AB  - We construct a natural measure on the space of Cabibbo-Kobayashi-Maskawa matrices
      in the standard model, assuming the fermion mass matrices are randomly selected
      from a distribution which incorporates the observed quark mass hierarchy. This
      measure allows us to assess the likelihood of Jarlskog's CP violation parameter J
      taking its observed value J approximately 3 x 10(-5). We find that the observed
      value, while well below the mathematically allowed maximum, is in fact typical
      once the observed quark masses are assumed.

PMID- 19392268
TI  - Structure of 240Pu: evidence for octupole phonon condensation?
AB  - The expanded level structure of 240Pu available from the present study highlights
      the role of strong octupole correlations in this nucleus. In addition to a
      delayed alignment in the yrast band, the observations include the presence of
      both I(+)-->(I-1)(-) and I(-)-->(I-1)(+)E1 transitions linking states of the
      yrast and negative-parity bands at high spin and the presence of an additional
      even-spin, positive-parity band deexciting exclusively to the negative-parity
      sequence. The observations appear to be consistent with expectations based on the
      recently proposed concept of octupole phonon condensation.

PMID- 19392269
TI  - Nuclear symmetry energy probed by neutron skin thickness of nuclei.
AB  - We describe a relation between the symmetry energy coefficients c(sym)(rho) of
      nuclear matter and a(sym)(A) of finite nuclei that accommodates other
      correlations of nuclear properties with the low-density behavior of c(sym)(rho).
      Here, we take advantage of this relation to explore the prospects for
      constraining c(sym)(rho) of systematic measurements of neutron skin sizes across
      the mass table, using as example present data from antiprotonic atoms. The found
      constraints from neutron skins are in harmony with the recent determinations from
      reactions and giant resonances.

PMID- 19392270
TI  - Schottky mass measurement of the 208Hg isotope: implication for the proton
      neutron interaction strength around doubly magic 208Pb.
AB  - Time-resolved Schottky mass spectrometry has been applied to uranium projectile
      fragments which yielded the mass value for the 208Hg (Z=80, N=128) isotope. The
      mass excess value of ME=-13 265(31) keV has been obtained, which has been used to
      determine the proton-neutron interaction strength in 210Pb, as a double
      difference of atomic masses. The results show a dramatic variation of the
      strength for lead isotopes when crossing the N=126 neutron shell closure, thus
      confirming the empirical predictions that this interaction strength is sensitive
      to the overlap of the wave functions of the last valence neutrons and protons.

PMID- 19392271
TI  - Constraints on the density dependence of the symmetry energy.
AB  - Collisions involving 112Sn and 124Sn nuclei have been simulated with the improved
      quantum molecular dynamics transport model. The results of the calculations
      reproduce isospin diffusion data from two different observables and the ratios of
      neutron and proton spectra. By comparing these data to calculations performed
      over a range of symmetry energies at saturation density and different
      representations of the density dependence of the symmetry energy, constraints on
      the density dependence of the symmetry energy at subnormal density are obtained.
      The results from the present work are compared to constraints put forward in
      other recent analyses.

PMID- 19392272
TI  - Nuclear interference in the Coulomb explosion of H2+ in short vuv laser fields.
AB  - We report ab initio calculations of H2+ three-photon ionization by vuv/fs 10(12)
      W/cm(2) laser pulses including electronic and vibrational degrees of freedom in
      the Born-Oppenheimer approximation. The initial nuclear wave packet of
      H2+(1ssigma(g)) is assumed to be equal to the H2 vibrational ground state. For
      pulse durations longer than 10 fs, we find an unexpected modulation in the
      kinetic energy spectra of the correlated fragments (H++H+). It is shown that the
      structures in the spectra originate from the interference between a direct and a
      sequential dissociation channel. While the first channel is open even for
      relatively short pulses, the sequential one only opens for pulse durations longer
      than 10 fs. In the latter case we show that interference between the two
      components results in a modulated kinetic energy release spectrum in the
      dissociation channel 3dsigma(g), which is reflected in the ionization spectrum.

PMID- 19392273
TI  - Few-photon multiple ionization of N2 by extreme ultraviolet free-electron laser
      radiation.
AB  - Few-photon multiple ionization of N2 was studied differentially in a reaction
      microscope using 44 eV, approximately 25 fs, intense ( approximately 10(13)
      W/cm(2)) photon pulses from FLASH. Sequential ionization is observed to dominate.
      For various intermediate charge states N(2)(n+0 we find a considerable excess of
      photons absorbed compared to the minimum number that would energetically be
      required. Photoionization of aligned N(2)(n+) ions, produced by photon absorption
      in sequential steps, is explored and few-photon absorption pathways are traced by
      inspecting kinetic energy releases and fragment-ion angular distributions.

PMID- 19392274
TI  - Attosecond photoelectron spectroscopy of metal surfaces.
AB  - Recent attosecond-streaking spectroscopy experiments [A. L. Cavalieri, Nature
      (London) 449, 1029 (2007)10.1038/nature06229] using copropagating extreme
      ultraviolet (XUV) and infrared (IR) pulses of variable relative delay have
      measured a delay of approximately 100 attoseconds between photoelectrons emitted
      by a single XUV photon from localized core states and delocalized conduction-band
      states of a tungsten surface. We analyze the underlying XUV-photoemission-IR
      streaking mechanism by combining a perturbative description of the XUV
      photoemission process and the subsequent nonperturbative IR streaking of the
      photoelectrons. Our calculated time-resolved photoelectron spectra agree with the
      experiments of Cavalieri et al. and demonstrate that the observed temporal shift
      is caused by the interference of core-level photoelectrons that originate in
      different layers of the solid.

PMID- 19392275
TI  - All optical waveguiding in a coherent atomic rubidium vapor.
AB  - We demonstrate an all optical waveguide imprinted by a low power Laguerre
      Gaussian control laser beam using a coherent Raman process in warm atomic
      rubidium vapor. We show that the signal beam propagates with a small spot size
      over several diffraction lengths. We also show that the coupling efficiency of
      the signal beam into the waveguide varies linearly with the signal power.

PMID- 19392276
TI  - Tailored photon-pair generation in optical fibers.
AB  - We experimentally control the spectral structure of photon pairs created via
      spontaneous four-wave mixing in microstructured fibers. By fabricating fibers
      with designed dispersion, one can manipulate the photons' wavelengths, joint
      spectrum, and, thus, entanglement. As an example, we produce photon pairs with no
      spectral correlations, allowing direct heralding of single photons in pure-state
      wave packets without filtering. We achieve an experimental purity of (85.9+/
      1.6)%, while theoretical analysis and preliminary tests suggest that 94.5% purity
      is possible with a much longer fiber.

PMID- 19392277
TI  - Determination of correlation functions of scattering potentials of stochastic
      media from scattering experiments.
AB  - The classic "Ewald-sphere construction" for determining the structure of
      crystalline objects from x-ray and neutron diffraction experiments is generalized
      to determine the correlation functions of scattering potentials of stationary
      random media from scattering experiments.

PMID- 19392278
TI  - Two-beam coupling between filament-forming beams in air.
AB  - We experimentally demonstrate two-beam coupling between nearly identical filament
      forming beams intersecting in air. A 7% amplification of one beam occurs at the
      energy expense of the other in a single interaction, controllable by adjusting
      their relative delay by tens of femtoseconds. The data are consistent with the
      impulsive Raman nonlinear response of the air molecules as the coupling
      mechanism. The filament conical emission is controllably enhanced or suppressed
      by the interaction, indicating that two-beam coupling may be an effective means
      for filament regeneration and control.

PMID- 19392279
TI  - Spin hall effect of light in spherical geometry.
AB  - Electromagnetic waves carry angular momenta, and, due to spin-orbit interaction,
      an encounter with a gradient of refractive index leads to transport of spin
      similar to the electronic spin Hall effect. We show here that transversal spin
      transport is possible even when the symmetry of optical interaction is of higher
      dimensionality. We demonstrate that for a wave in a pure state of polarization,
      the spin-orbit interaction results in a spiraling power flow that is determined
      by the extent of the interaction. As a result, the spin transport can be
      resonantly enhanced in a spherical geometry. Our results open the possibility for
      developing new functionalities for photonic devices.

PMID- 19392280
TI  - Dirac spectra and edge states in honeycomb plasmonic lattices.
AB  - We study theoretically the dispersion of plasmonic honeycomb lattices and find
      Dirac spectra for both dipole and quadrupole modes. Zigzag edge states derived
      from Dirac points are found in ribbons of these honeycomb plasmonic lattices. The
      zigzag edge states for out-of-plane dipole modes are closely analogous to the
      electronic ones in graphene nanoribbons. The edge states for in-plane dipole
      modes and quadrupole modes, however, have rather unique characters due to the
      vector nature of the plasmonic excitations. The conditions for the existence of
      plasmonic edge states are derived analytically.

PMID- 19392281
TI  - Experimental observation of Rabi oscillations in photonic lattices.
AB  - We demonstrate spatial Rabi oscillations in optical waveguide arrays. Adiabatic
      transitions between extended Floquet-Bloch modes associated with different bands
      are stimulated by periodic modulation of the photonic lattice in the propagation
      direction. When the stimulating modulation also carries transverse momentum, the
      transition becomes indirect, equivalent to phonon-assisted Rabi oscillations. In
      solid state physics such indirect Rabi oscillations necessitate coherent phonons
      and hence they have never been observed. Our experiments suggest that phonon
      assisted Rabi oscillations are observable also with Bose-Einstein condensates, as
      well as with other wave systems-where coherence can be maintained for at least
      one period of the Rabi oscillation.

PMID- 19392266
TI  - Inclusive search for squark and gluino production in pp[over ] collisions at
      sqrt[s]=1.96 TeV.
AB  - We report on a search for inclusive production of squarks and gluinos in pp[over
      ] collisions at sqrt[s]=1.96 TeV, in events with large missing transverse energy
      and multiple jets of hadrons in the final state. The study uses a CDF Run II data
      sample corresponding to 2 fb(-1) of integrated luminosity. The data are in good
      agreement with the standard model predictions, giving no evidence for any squark
      or gluino component. In an R-parity conserving minimal supergravity scenario with
      A(0)=0, mu<0, and tanbeta=5, 95% C.L. upper limits on the production cross
      sections in the range between 0.1 and 1 pb are obtained, depending on the squark
      and gluino masses considered. For gluino masses below 280 GeV/c(2), arbitrarily
      large squark masses are excluded at the 95% C.L., while for mass degenerate
      gluinos and squarks, masses below 392 GeV/c(2) are excluded at the 95% C.L.

PMID- 19392282
TI  - Directing Brownian motion on a periodic surface.
AB  - We consider an overdamped Brownian particle, exposed to a two-dimensional, square
      lattice potential and a rectangular ac drive. Depending on the driving amplitude,
      the linear response to a weak dc force along a lattice symmetry axis consist in a
      mobility in basically any direction. In particular, motion exactly opposite to
      the applied dc force may arise. Upon changing the angle of the dc force
      relatively to the square lattice, the particle motion remains predominantly
      opposite to the dc force. The basic physical mechanism consists in a spontaneous
      symmetry breaking of the unbiased deterministic particle dynamics.

PMID- 19392284
TI  - Selection rules for the nonlinear interaction of internal gravity waves.
AB  - Two intersecting beams of internal gravity waves will generically create two wave
      packets by nonlinear interaction. The frequency of one packet will be the sum and
      that of the other packet will be the difference of the frequencies of the
      intersecting beams. In principle, each packet should form an "X" pattern, or "St.
      Andrew's cross" consisting of four beams outgoing from the point of intersection.
      Here we derive selection rules and show that most of the expected nonlinear beams
      are forbidden. These rules can also be applied to the reflection of a beam from a
      boundary.

PMID- 19392283
TI  - Enhanced heat transport by turbulent two-phase Rayleigh-Benard convection.
AB  - We report measurements of turbulent heat transport in samples of ethane (C2H6)
      heated from below while the applied temperature difference DeltaT straddled the
      liquid-vapor coexistence curve T(phi)(P). When the sample top temperature T(t)
      decreased below T(phi), droplet condensation occurred and the latent heat of
      vaporization H provided an additional heat-transport mechanism. The effective
      conductivity lambda(eff) increased linearly with decreasing T(t), and reached a
      maximum value lambda(eff)(*) that was an order of magnitude larger than the
      single-phase lambda(eff). As P approached the critical pressure, lambda(eff)(*)
      increased dramatically even though H vanished. We attribute this phenomenon to an
      enhanced droplet-nucleation rate as the critical point is approached.

PMID- 19392285
TI  - Power and pressure fluctuations in elastic turbulence over a wide range of
      polymer concentrations.
AB  - Injected power P and pressure p fluctuations in a swirling flow of polymer
      solutions in a wide range of polymer concentrations c in elastic turbulence
      regime show non-Gaussian statistics that strongly resemble statistical behavior
      of P and p in hydrodynamic turbulence. Together with this fact, weak dependence
      of the statistics of rescaled variables on c may suggest that there are universal
      mechanisms determining the intermittent statistics of P and p. We also show that
      the study of the statistics of p provides a way to study statistics of the
      elastic stresses in elastic turbulence otherwise currently unattainable.

PMID- 19392286
TI  - Wave-current interaction as a spatial dynamical system: analogies with rainbow
      and black hole physics.
AB  - We study the hydrodynamic phenomenon of waves blocking by a countercurrent with
      the tools of dynamical systems theory. We show that, for a uniform background
      velocity and within the small wavelength approximation, the stopping of gravity
      waves is described by a stationary saddle-node bifurcation due to the spatial
      resonance of an incident wave with the converted "blueshifted" wave. We explain
      why the classical regularization effect of interferences avoids the height
      singularity in complete analogy with the intensity of light close to the
      principal arc of a rainbow. The application to the behavior of light near a
      gravitational horizon is discussed.

PMID- 19392287
TI  - Interacting vortices and spin-up in two-dimensional turbulence.
AB  - In simulations of decaying two-dimensional turbulence, Clercx and co-workers
      discovered the unexpected phenomenon of "spin-up." (This is the spontaneous
      acquisition of angular momentum by a turbulent two-dimensional fluid in a rigid
      container.) Here we show that this phenomenon can readily be interpreted in terms
      of statistical models of two-dimensional turbulence. When the net vorticity is
      zero in a bounded system, there are two distinct types of statistical
      equilibrium. The first has the expected property that its angular momentum is
      zero. However, the second type has a nonzero angular momentum even though its
      circulation vanishes. The relative probability of the two types of equilibrium
      depends strongly on the shape of the boundary and weakly on the energy. The
      angular momentum predicted for the second type of equilibrium is in good
      agreement with that found in simulations at high Reynolds number.

PMID- 19392288
TI  - Few-cycle laser-driven electron acceleration.
AB  - We report on an electron accelerator based on few-cycle (8 fs full width at half
      maximum) laser pulses, with only 40 mJ energy per pulse, which constitutes a
      previously unexplored parameter range in laser-driven electron acceleration. The
      produced electron spectra are monoenergetic in the tens-of-MeV range and
      virtually free of low-energy electrons with thermal spectrum. The electron beam
      has a typical divergence of 5-10 mrad. The accelerator is routinely operated at
      10 Hz and constitutes a promising source for several applications. Scalability of
      the few-cycle driver in repetition rate and energy implies that the present work
      also represents a step towards user friendly laser-based accelerators.

PMID- 19392289
TI  - Transport of parallel momentum induced by current-symmetry breaking in toroidal
      plasmas.
AB  - The symmetry of a physical system strongly impacts on its properties. In toroidal
      plasmas, the symmetry along a magnetic field line usually constrains the radial
      flux of parallel momentum to zero in the absence of background flows. By breaking
      the up-down symmetry of the toroidal currents, this constraint can be relaxed.
      The parallel asymmetry in the magnetic configuration then leads to an incomplete
      cancellation of the turbulent momentum flux across a flux surface. The magnitude
      of the subsequent toroidal rotation increases with the up-down asymmetry and its
      sign depends on the direction of the toroidal magnetic field and plasma current.
      Such a mechanism offers new insights in the interpretation and control of the
      intrinsic toroidal rotation in present day experiments.

PMID- 19392290
TI  - Characterization of high-intensity laser propagation in the relativistic
      transparent regime through measurements of energetic proton beams.
AB  - Experiments were performed to investigate the propagation of a high intensity (I
      approximately 10(21) W cm(-2)) laser in foam targets with densities ranging from
      0.9n(c) to 30n(c). Proton acceleration was used to diagnose the interaction. An
      improvement in proton beam energy and efficiency is observed for the lowest
      density foam (n(e)=0.9n(c)), compared to higher density foams. Simulations show
      that the laser beam penetrates deeper into the target due to its relativistic
      propagation and results in greater collimation of the ensuing hot electrons. This
      results in the rear surface accelerating electric field being larger, increasing
      the efficiency of the acceleration. Enhanced collimation of the ions is seen to
      be due to the self-generated azimuthal magnetic and electric fields at the rear
      of the target.

PMID- 19392291
TI  - Quantum phase transitions and continuous observation of spinor dynamics in an
      antiferromagnetic condensate.
AB  - Condensates of spin-1 sodium display rich spin dynamics due to the
      antiferromagnetic nature of the interactions in this system. We use Faraday
      rotation spectroscopy to make a continuous and minimally destructive measurement
      of the dynamics over multiple spin oscillations on a single evolving condensate.
      This method provides a sharp signature to locate a magnetically tuned separatrix
      in phase space which depends on the net magnetization. We also observe a phase
      transition from a two- to a three-component condensate at a low but finite
      temperature using a Stern-Gerlach imaging technique. This transition should be
      preserved as a zero-temperature quantum phase transition.

PMID- 19392292
TI  - Heat capacity peak in solid 4He: effects of disorder and 3He impurities.
AB  - Heat capacity measurements with significantly improved resolution find the
      presence of a peak in a solid 4He sample in coexistence with liquid. With
      improved crystallinity, the peak decreases in height and moves to lower
      temperature. A hysteretic heat capacity signature consistent with 3He-4He phase
      separation, not detected in an earlier work is clearly observed.

PMID- 19392293
TI  - An in-plane solid-liquid-solid growth mode for self-avoiding lateral silicon
      nanowires.
AB  - We report an in-plane solid-liquid-solid (IPSLS) mode for obtaining self-avoiding
      lateral silicon nanowires (SiNW) in a reacting-gas-free annealing process, where
      the growth of SiNWs is guided by liquid indium drops that transform the
      surrounding a-SiratioH matrix into crystalline SiNWs. The SiNWs can be
      approximately mm long, with the smallest diameter down to approximately 22 nm. A
      high growth rate of >10(2) nm/s and rich evolution dynamics are revealed in a
      real-time in situ scanning electron microscopy observation. A qualitative growth
      model is proposed to account for the major features of this IPSLS SiNW growth
      mode.

PMID- 19392294
TI  - Dynamical chiral symmetry breaking in sliding nanotubes.
AB  - We discover in simulations of sliding coaxial nanotubes an unanticipated example
      of dynamical symmetry breaking taking place at the nanoscale. While both
      nanotubes are perfectly left-right symmetric and nonchiral, a nonzero angular
      momentum of phonon origin appears spontaneously at a series of critical sliding
      velocities, in correspondence with large peaks of the sliding friction. The
      nonlinear equations governing this phenomenon resemble the rotational instability
      of a forced string. However, several new elements, exquisitely "nano" appear
      here, with the crucial involvement of umklapp and of sliding nanofriction.

PMID- 19392295
TI  - Impact of phonon-surface roughness scattering on thermal conductivity of thin si
      nanowires.
AB  - We present a novel approach for computing the surface roughness-limited thermal
      conductivity of silicon nanowires with diameter D<100 nm. A frequency-dependent
      phonon scattering rate is computed from perturbation theory and related to a
      description of the surface through the root-mean-square roughness height Delta
      and autocovariance length L. Using a full phonon dispersion relation, we find a
      quadratic dependence of thermal conductivity on diameter and roughness as
      (D/Delta)(2). Computed results show excellent agreement with experimental data
      for a wide diameter and temperature range (25-350 K), and successfully predict
      the extraordinarily low thermal conductivity of 2 W m(-1) K-1 at room temperature
      in rough-etched 50 nm silicon nanowires.

PMID- 19392296
TI  - Statistical mechanics and dynamics of a three-dimensional glass-forming system.
AB  - In the context of a classical example of glass formation in three dimensions, we
      exemplify how to construct a statistical-mechanical theory of the glass
      transition. At the heart of the approach is a simple criterion for verifying a
      proper choice of upscaled quasispecies that allow the construction of a theory
      with a finite number of "states." Once constructed, the theory identifies a
      typical scale xi that increases rapidly with lowering the temperature and which
      determines the alpha-relaxation time tau(alpha) as tau(alpha) approximately
      exp(muxi/T), with mu a typical chemical potential. The theory can predict
      relaxation times at temperatures that are inaccessible to numerical simulations.

PMID- 19392297
TI  - High-pressure phases of nitrogen.
AB  - Density-functional-theory calculations and a structure-searching method are used
      to identify candidate high-pressure phases of nitrogen. We find six structures
      which are calculated to be more stable than previously studied structures at some
      pressures. Our four new molecular structures give insight into the most efficient
      packings of nitrogen molecules at high pressures, and we predict two new
      nonmolecular structures to be stable at very high pressures.

PMID- 19392298
TI  - Local methylthiolate adsorption geometry on Au(111) from photoemission core-level
      shifts.
AB  - The local adsorption structure of methylthiolate in the ordered Au(111)
      (sqrt[3]xsqrt[3])R30 degrees phase has been investigated using core-level-shift
      measurements of the surface and bulk components of the Au 4f(7/2) photoelectron
      binding energy. The amplitude ratio of the core-level-shift components associated
      with surface Au atoms that are, and are not, bonded to the thiolate is found to
      be compatible only with the previously proposed Au-adatom-monothiolate moiety in
      which the thiolate is bonded atop Au adatoms in hollow sites, and not on an
      unreconstructed surface, or in Au-adatom-dithiolate species.

PMID- 19392299
TI  - Orbital-selective Mott transition out of band degeneracy lifting.
AB  - We outline a general mechanism for orbital-selective Mott transition, the
      coexistence of both itinerant and localized conduction electrons, and show how it
      can take place in a wide range of realistic situations, even for bands of
      identical width and correlation, provided a crystal field splits the energy
      levels in manifolds with different degeneracies and the exchange coupling is
      large enough to reduce orbital fluctuations. The mechanism relies on the
      different kinetic energy in manifolds with different degeneracy. This phase has
      Curie-Weiss susceptibility and non-Fermi-liquid behavior, which disappear at a
      critical doping, all of which is reminiscent of the physics of the pnictides.

PMID- 19392300
TI  - Phase diagram of the low-density two-dimensional homogeneous electron gas.
AB  - We use quantum Monte Carlo methods to calculate the zero-temperature phase
      diagram of the two-dimensional homogeneous electron gas. We find a transition
      from a paramagnetic fluid to an antiferromagnetic triangular Wigner crystal at
      density parameter r(s)=31(1) a.u. and a transition to a ferromagnetic crystal at
      r(s)=38(5) a.u. The fully spin-polarized fluid is never stable. We search for,
      but do not find, the ferromagnetic "hybrid" phase proposed by H. Falakshahi and
      X. Waintal [Phys. Rev. Lett. 94, 046801 (2005)10.1103/PhysRevLett.94.046801].

PMID- 19392301
TI  - Localized and itinerant states in lanthanide oxides united by GW @ LDA+U.
AB  - Many-body perturbation theory in the GW approach is applied to lanthanide oxides,
      using the local-density approximation plus a Hubbard U correction (LDA+U) as the
      starting point. Good agreement between the G0W0 density of states and
      experimental spectra is observed for CeO2 and Ce2O3. Unlike the LDA+U method G0W0
      exhibits only a weak dependence on U in a physically meaningful range of U
      values. For the whole lanthanide sesquioxide (Ln2O3) series G0W0 @ LDA+U
      reproduces the main features found for the optical experimental band gaps. The
      relative positions of the occupied and unoccupied f states predicted by G0W0
      confirm the experimental conjecture derived from phenomenological arguments.

PMID- 19392302
TI  - Stationary density matrix of a pumped polariton system.
AB  - The density matrix rho of a model polariton system is obtained numerically from a
      master equation which takes account of pumping and losses. In the stationary
      limit, the coherences between eigenstates of the Hamiltonian are 3 orders of
      magnitude smaller than the occupations, meaning that the stationary density
      matrix is approximately diagonal in the energy representation. A weakly distorted
      grand canonical Gibbs distribution fits well the occupations.

PMID- 19392303
TI  - Phenomenology of one-dimensional quantum liquids beyond the low-energy limit.
AB  - We consider the zero temperature behavior of dynamic response functions of 1D
      systems near edges of support in the momentum-energy plane (k,omega). The
      description of the singularities of dynamic response functions near an edge
      epsilon(k) is given by the effective Hamiltonian of a mobile impurity moving in a
      Luttinger liquid. For Galilean-invariant systems, we relate the parameters of
      such an effective Hamiltonian to the properties of the function epsilon(k). This
      allows us to express the exponents which characterize singular response functions
      of spinless bosonic or fermionic liquids in terms of epsilon(k) and Luttinger
      liquid parameters for any k. For an antiferromagnetic Heisenberg spin-1/2 chain
      in a zero magnetic field, SU(2) invariance fixes the exponents from purely
      phenomenological considerations.

PMID- 19392304
TI  - Aharonov-Casher effect in exchange interactions in a Wigner crystal.
AB  - We theoretically study the effects of spin-orbit coupling on spin exchange in a
      low-density Wigner crystal. In addition to the familiar antiferromagnetic
      Heisenberg exchange, we find general anisotropic interactions in spin space if
      the exchange paths allowed by the crystal structure form loops in real space. In
      particular, it is shown that the two-electron exchange interaction can acquire
      ferromagnetic character.

PMID- 19392305
TI  - Random-gap model for graphene and graphene bilayers.
AB  - The effect of a randomly fluctuating gap, created by a random staggered
      potential, is studied in a monolayer and a bilayer of graphene. The density of
      states, the one-particle scattering rate, and the transport properties (diffusion
      coefficient and conductivity) are calculated at the neutrality point. All of
      these quantities vanish at a critical value of the average staggered potential,
      signaling a continuous transition to an insulating behavior. Transport quantities
      are directly linked to the one-particle scattering rate. Although the behavior is
      qualitatively the same in mono- and bilayers, the effect of disorder is much
      stronger in the latter.

PMID- 19392306
TI  - Formation and evolution of single-molecule junctions.
AB  - We analyze the formation and evolution statistics of single-molecule junctions
      bonded to gold electrodes using amine, methyl sulfide, and dimethyl phosphine
      link groups by measuring conductance as a function of junction elongation. For
      each link, the maximum elongation and formation probability increase with
      molecular length, strongly suggesting that processes other than just metal
      molecule bond breakage play a key role in junction evolution under stress.
      Density functional theory calculations of adiabatic trajectories show sequences
      of atomic-scale changes in junction structure, including shifts in the attachment
      point, that account for the long conductance plateau lengths observed.

PMID- 19392307
TI  - Softening of the radial breathing mode in metallic carbon nanotubes.
AB  - The softening of the radial breathing mode (RBM) of metallic single walled carbon
      nanotubes (m-SWNTs) due to electron-phonon coupling has been studied by observing
      the Fermi level [see text] dependence of the RBM Raman peak. In situ Raman
      spectra were obtained from several individual m-SWNTs while varying [see text]
      electrochemically. The RBM frequency of an intrinsic m-SWNT is shown to be down
      shifted relative to highly doped tubes by approximately 2 cm(1). The down-shift
      is greatest for small diameter and small chiral angle SWNTs. Most tubes show no
      change in RBM linewidth. A comparison is drawn between the RBM and the G band
      (A(LO) phonon) with respect to the [see text] dependence of their frequencies and
      linewidths.

PMID- 19392308
TI  - Resistance noise in electrically biased bilayer graphene.
AB  - We demonstrate that the low-frequency resistance fluctuations, or noise, in
      bilayer graphene are strongly connected to its band structure and display a
      minimum when the gap between the conduction and valence band is zero. Using
      double-gated bilayer graphene devices we have tuned the zero gap and charge
      neutrality points independently, which offers a versatile mechanism to
      investigate the low-energy band structure, charge localization, and screening
      properties of bilayer graphene.

PMID- 19392309
TI  - Optical absorption to probe the quantum Hall ferromagnet at filling factor nu=1.
AB  - Optical absorption measurements are used to probe the spin polarization in the
      integer and fractional quantum Hall effect regimes. The system is fully spin
      polarized only at filling factor nu=1 and at very low temperatures (
      approximately 40 mK). A small change in filling factor (deltanu approximately +/
      0.01) leads to a significant depolarization. This suggests that the itinerant
      quantum Hall ferromagnet at nu=1 is surprisingly fragile against increasing
      temperature, or against small changes in filling factor.

PMID- 19392310
TI  - Embedding transition-metal atoms in graphene: structure, bonding, and magnetism.
AB  - We present a density-functional-theory study of transition-metal atoms (Sc-Zn,
      Pt, and Au) embedded in single and double vacancies (SV and DV) in a graphene
      sheet. We show that for most metals, the bonding is strong and the metal-vacancy
      complexes exhibit interesting magnetic behavior. In particular, an Fe atom on a
      SV is not magnetic, while the Fe@DV complex has a high magnetic moment.
      Surprisingly, Au and Cu atoms at SV are magnetic. Both bond strengths and
      magnetic moments can be understood within a simple local-orbital picture,
      involving carbon sp(2) hybrids and the metal spd orbitals. We further calculate
      the barriers for impurity-atom migration, and they agree well with available
      experimental data. We discuss the experimental realization of such systems in the
      context of spintronics and nanocatalysis.

PMID- 19392311
TI  - Effect of microwaves on the current-phase relation of superconductor-normal-metal
      superconductor josephson junctions.
AB  - We investigate the current-phase relation (CPR) of long diffusive superconductor
      normal-metal-superconductor (Nb/Ag/Nb) Josephson junctions in thermodynamic
      equilibrium and under microwave irradiation. While in equilibrium good agreement
      with the predictions of quasiclassical theory is found, we observe that the shape
      of the CPR can be strongly affected by microwave irradiation. Close to a
      Josephson-phase difference phi approximately pi, the supercurrent can be strongly
      suppressed when increasing the rf power. Our results can be understood in terms
      of microwave excitation of low-lying Andreev bound states across the minigap in
      the junction. In the frequency interval studied, this mechanism becomes
      important, when the minigap closes at phi approximately pi.

PMID- 19392312
TI  - Mechanism of terahertz electromagnetic wave emission from intrinsic Josephson
      junctions.
AB  - Using a 3D parallelepiped model of the stack of intrinsic Josephson junctions, we
      calculate the cavity resonance modes of Josephson plasma waves excited by
      external electric currents. The cavity modes accompanied by static phase kinks of
      the order parameter have been intensively investigated. Our calculation shows
      that the kink phase state is unfavorable, since the static phase kinks reduce the
      order parameter amplitude and thus the superconducting condensation energy. We
      point out that the oscillating magnetic field of the cavity mode penetrates the
      vacuum from the sample surfaces and the energy of the magnetic field plays an
      important role to determine the orientation of the cavity resonance mode. On the
      basis of the above discussions, we calculate the I-V characteristic curve, the
      THz wave emission intensity and the other physical quantities.

PMID- 19392313
TI  - Unusual doping dependence of the electronic structure and coexistence of spin
      density-wave and superconductor phases in single crystalline Sr1-xKxFe2As2.
AB  - The nature of the spin-density wave (SDW) and its relation with superconductivity
      are crucial issues in the newly discovered iron-pnictide superconductors.
      Particularly, it is unclear whether the superconducting phase and SDW are truly
      exclusive from each other. We here report splittings of the band structures in
      Sr1-xKxFe2As2 (x=0, 0.1, 0.18), and their unusual doping dependence. Our data on
      single crystalline samples prove that the SDW and superconductivity could coexist
      in iron pnictides.

PMID- 19392314
TI  - Unconventional London penetration depth in single-crystal Ba(Fe0.93Co0.07)2As2
      superconductors.
AB  - The London penetration depth lambda(T) has been measured in single crystals of
      Ba(Fe0.93Co0.07)2As2. The observed low-temperature variation of lambda(T) follows
      a power law, Deltalambda(T) approximately T(n) with n approximately 2.4+/-0.1,
      indicating the existence of normal quasiparticles down to at least 0.02T(c). This
      is in contrast with previous penetration depth measurements on single crystals of
      NdFeAsO1-xFx and SmFeAsO1-xFx, which indicate an anisotropic but nodeless gap. We
      discuss possible explanations of the observed power law behavior.

PMID- 19392315
TI  - Ultimate vortex confinement studied by scanning tunneling spectroscopy.
AB  - We report a detailed scanning tunneling microscopy study of a superconductor in a
      strong vortex confinement regime. This is achieved in a thin nanoisland of Pb
      having a size d about 3 times the coherence length, and a thickness h such that
      h<<d<<lambda, where lambda is the London penetration depth. In this geometry the
      magnetic field evolution of local tunneling spectra reveals only two
      superconducting configurations to exist: zero and single vorticity. The normal
      state is reached at mu(0)H(c)=0.46 T, about 6 times the critical field of bulk
      Pb, with no higher order vorticity observed. Basing on our STS data, we discuss
      the role of local supercurrents in both configurations.

PMID- 19392316
TI  - Role of nanoscale precipitates on the enhanced magnetostriction of heat-treated
      galfenol (Fe1-xGax) alloys.
AB  - We report neutron diffuse scattering measurements on highly magnetostrictive Fe1
      xGax alloys (0.14<x<0.20) with different thermal treatments. This diffuse
      scattering scales with magnetostriction and exhibits asymmetric peaks at the
      (100) and (300) reciprocal lattice positions that are consistent with the
      coexistence of short-range ordered, coherent nanometer-scale precipitates
      embedded in a long-range ordered, body-centered cubic matrix. A large peak
      splitting is observed at (300) for x=0.19, which indicates that the
      nanoprecipitates are not cubic and have a large elastic strain. This implies a
      structural origin for the enhanced magnetostriction.

PMID- 19392317
TI  - Physical origin and generic control of magnonic band gaps of dipole-exchange spin
      waves in width-modulated nanostrip waveguides.
AB  - We report, for the first time, on a novel planar structure of magnonic-crystal
      waveguides, made of a single magnetic material, in which the allowed and
      forbidden bands of propagating dipole-exchange spin waves can be manipulated by
      the periodic modulation of different widths in thin-film nanostrips. The origin
      of the presence of several magnonic wide band gaps and the crucial parameters for
      controlling those band gaps of the order of approximately 10 GHz are found by
      micromagnetic numerical and analytical calculations. This work can offer a route
      to the potential application to broadband spin wave filters in the gigahertz
      frequency range.

PMID- 19392318
TI  - Dependence of domain-wall depinning threshold current on pinning profile.
AB  - We have investigated the threshold current density required for depinning a
      domain wall from constrictions in NiFe nanowires, which give rise to pinning
      potentials of fixed amplitude but variable profile. We observed it to vary
      linearly with the angle of the triangular constriction. These results are
      reproduced using micromagnetic simulations including the adiabatic and
      nonadiabatic spin-torque terms. By curve-fitting the calculated variations to the
      experimental results, we obtain the nonadiabaticity parameter beta=0.04(+/-0.005)
      and current spin polarization P=0.51(+/-0.02).

PMID- 19392319
TI  - Effective thermal dynamics following a quantum quench in a spin chain.
AB  - We study the nonequilibrium dynamics of the quantum Ising model following an
      abrupt quench of the transverse field. We focus on the on-site autocorrelation
      function of the order parameter, and extract the phase-coherence time tau(Q)(phi)
      from its asymptotic behavior. We show that the initial state determines
      tau(Q)(phi) only through an effective temperature set by its energy and the final
      Hamiltonian. Moreover, we observe that the dependence of tau(Q)(phi) on the
      effective temperature fairly agrees with that obtained in thermal equilibrium as
      a function of the equilibrium temperature.

PMID- 19392320
TI  - Spin configuration in the 1/3 magnetization plateau of azurite determined by NMR.
AB  - High magnetic field (63,65)Cu NMR spectra were used to determine the local spin
      polarization in the 1/3 magnetization plateau of azurite, Cu3(CO3)(2)(OH)(2),
      which is a model system for the distorted diamond antiferromagnetic spin-1/2
      chain. The spin part of the hyperfine field of the Cu2 (dimer) sites is found to
      be field independent, negative and strongly anisotropic, corresponding to
      approximately 10% of fully polarized spin in a d orbital. This is close to the
      expected configuration of the quantum plateau, where a singlet state is
      stabilized on the dimer. However, the observed nonzero spin polarization points
      to some triplet admixture, induced by strong asymmetry of the diamond bonds J1
      and J3.

PMID- 19392321
TI  - Coherent phonon dynamics in semiconducting carbon nanotubes: a quantitative study
      of electron-phonon coupling.
AB  - We excite and detect coherent phonons in semiconducting (6,5) carbon nanotubes
      via a sub-10-fs pump-probe technique. Simulation of the amplitude and phase
      profile via time-dependent wave packet theory yields excellent agreement with
      experimental results under the assumption of molecular excitonic states and
      allows determining the electron-phonon coupling strength for the two dominant
      vibrational modes.

PMID- 19392322
TI  - Optical spin orientation of a single manganese atom in a semiconductor quantum
      dot using quasiresonant photoexcitation.
AB  - An optical spin orientation is achieved for a Mn atom localized in a
      semiconductor quantum dot using quasiresonant excitation at zero magnetic field.
      Optically created spin-polarized carriers generate an energy splitting of the Mn
      spin and enable magnetic moment orientation controlled by the photon helicity and
      energy. The dynamics and the magnetic field dependence of the optical pumping
      mechanism show that the spin lifetime of an isolated Mn atom at zero magnetic
      field is controlled by a magnetic anisotropy induced by the built-in strain in
      the quantum dots.

PMID- 19392323
TI  - Fano signatures in the intersubband terahertz response of optically excited
      semiconductor quantum wells.
AB  - Absorption and transmission spectra of broadband terahertz pulses are measured to
      probe the intersubband response of an optically excited quantum-well
      heterostructure. While the terahertz absorption shows the single peak of the
      resonant intersubband transition, the transmission spectra display strong Fano
      signatures due to the phase sensitive superposition of ponderomotive and
      terahertz currents as predicted by our microscopic theory.

PMID- 19392324
TI  - Gain control in semiconductor quantum dots via state-resolved optical pumping.
AB  - Excitonic state-resolved optical pumping experiments were performed on strongly
      confined semiconductor quantum dots. We demonstrate for the first time that
      optical gain is dependent upon the initial excitonic state. By prescribing the
      specific multiexcitonic states which can create, block, and ultimately control
      optical gain spectra, we recover the theoretically predicted size independence,
      even in systems which previously showed zero gain. In addition, we show for the
      first time that stimulated emission in quantum dots can be controlled via
      specific multiexcitonic interactions.

PMID- 19392325
TI  - Optical nonlocalities and additional waves in epsilon-near-zero metamaterials.
AB  - We analyze the optical properties of plasmonic nanorod metamaterials in the
      epsilon-near-zero regime and show, both theoretically and experimentally, that
      the performance of these composites is strongly affected by nonlocal response of
      the effective permittivity tensor. We provide the evidence of interference
      between main and additional waves propagating in the room-temperature nanorod
      metamaterials and develop an analytical description of this phenomenon.
      Additional waves are present in the majority of low-loss epsilon-near-zero
      structures and should be explicitly considered when designing applications of
      epsilon-near-zero composites, as they represent a separate communication channel.

PMID- 19392326
TI  - Bimodal spectrum for the curvature fluctuations of bilayer vesicles: pure bending
      plus hybrid curvature-dilation modes.
AB  - We study thermal undulations of giant bilayer vesicles by flickering
      spectroscopy. The experimental fluctuation spectra are scrutinized in view of the
      classical Helfrich theory. Pure bending modes are revealed to be unable to
      predict the large fluctuations systematically found at a high wave vector. Hybrid
      curvature-dilational modes are then invoked as a more efficient mode of motion in
      producing high curvatures. A bimodal spectrum of the thermal undulations has been
      theoretically developed for the shell-like topology. Reconciliation between
      experiments and theory is achieved when this bimodal spectrum is considered.

PMID- 19392327
TI  - Laser-driven nanoplasmas in doped helium droplets: local ignition and anisotropic
      growth.
AB  - Doping a helium nanodroplet with only a tiny xenon cluster of a few atoms sparks
      complete ionization of the droplet at laser intensities below the ionization
      threshold of helium atoms. As a result, the intrinsically inert and transparent
      droplet turns into a fast and strong absorber of infrared light. Microscopic
      calculations reveal a two-step mechanism to be responsible for the dramatic
      change: Avalanchelike ionization of the helium atoms on a femtosecond time scale,
      driven by field ionization due to the quickly charged xenon core, is followed by
      resonant absorption enabled by an unusual cigar-shaped nanoplasma within the
      droplet.

PMID- 19392328
TI  - Do multilayer crystals nucleate in suspensions of colloidal rods?
AB  - We study the isotropic-to-crystal transformation in a mixture of colloidal hard
      rods and nonabsorbing polymer using computer simulations. We determine the height
      of the nucleation barrier and find that the critical cluster consists of a single
      crystalline layer growing laterally for all polymer fugacities considered. At
      lower supersaturation, the free energy of a single hexagonally packed layer
      increases monotonically with size, while the nucleation barrier of a second
      crystalline layer is extremely high. Hence, the nucleation of multilayer crystals
      is never observed. Multilayer crystals form only in the spinodal decomposition
      regime, either where, in an intermediate stage, single crystalline membranes
      coalesce into multilayer clusters or where, at higher polymer fugacity, smaller
      clusters of rods stack on top of each other to form long filaments. Eventually,
      these transient structures evolve into a thermodynamically stable bulk crystal
      phase.

PMID- 19392329
TI  - Stretching, unfolding, and deforming protein filaments adsorbed at solid-liquid
      interfaces using the tip of an atomic-force microscope.
AB  - Cells move by actively remodeling a dense network of protein filaments. Here we
      analyze the force response of various filaments in a simplified experimental
      setup, where single filaments are moved with an atomic-force microscope (AFM) tip
      against surface friction, with the AFM operating in the torsional mode. Our
      experimental findings are well explained within a simple model based on Newtonian
      mechanics: we observe force plateaus, which are the signature of the sequential
      stretching of single repeat units, followed ultimately by deformation of the
      whole polymer shape.

PMID- 19392330
TI  - Random acyclic networks.
AB  - Directed acyclic graphs make up a fundamental class of networks that includes
      citation networks, food webs, and family trees, among others. Here we define a
      random graph model for directed acyclic graphs and give solutions for a number of
      the model's properties, including connection probabilities and component sizes,
      as well as a fast algorithm for simulating the model on a computer. We compare
      the predictions of the model to a real-world network of citations between physics
      papers and find surprisingly good agreement, suggesting that the structure of the
      real network may be quite well described by the random graph.

PMID- 19392331
TI  - Comment on "dipolar excitations at the LIII X-ray absorption edges of the heavy
      rare-earth metals".

PMID- 19392333
TI  - Comment on "asymptotic strength limit of hydrogen-bond assemblies in proteins at
      vanishing pulling rates".

PMID- 19392335
TI  - Bose-Einstein condensate in a uniform light-induced vector potential.
AB  - We use a two-photon dressing field to create an effective vector gauge potential
      for Bose-Einstein-condensed 87Rb atoms in the F=1 hyperfine ground state. These
      Raman-dressed states are spin and momentum superpositions, and we adiabatically
      load the atoms into the lowest energy dressed state. The effective Hamiltonian of
      these neutral atoms is like that of charged particles in a uniform magnetic
      vector potential whose magnitude is set by the strength and detuning of the Raman
      coupling. The spin and momentum decomposition of the dressed states reveals the
      strength of the effective vector potential, and our measurements agree
      quantitatively with a simple single-particle model. While the uniform effective
      vector potential described here corresponds to zero magnetic field, our technique
      can be extended to nonuniform vector potentials, giving nonzero effective
      magnetic fields.

PMID- 19392336
TI  - Continuous-variable quantum key distribution protocols over noisy channels.
AB  - A continuous-variable quantum key distribution protocol based on squeezed states
      and heterodyne detection is introduced and shown to attain higher secret key
      rates over a noisy line than any other one-way Gaussian protocol. This increased
      resistance to channel noise can be understood as resulting from purposely adding
      noise to the signal that is converted into the secret key. This notion of noise
      enhanced tolerance to noise also provides a better physical insight into the
      poorly understood discrepancies between the previously defined families of
      Gaussian protocols.

PMID- 19392337
TI  - Local transformation of two einstein-podolsky-rosen photon pairs into a three
      photon w state.
AB  - We propose and experimentally demonstrate a transformation of two Einstein
      Podolsky-Rosen photon pairs distributed among three parties into a three-photon W
      state using local operations and classical communication. We then characterize
      the final state using quantum state tomography on the three-photon state and on
      its marginal bipartite states. The fidelity of the final state to the ideal W
      state is 0.778+/-0.043 and the expectation value for its witness operator is 
      0.111+/-0.043 implying the success of the proposed local transformation.

PMID- 19392338
TI  - Preparing ground States of quantum many-body systems on a quantum computer.
AB  - Preparing the ground state of a system of interacting classical particles is an
      NP-hard problem. Thus, there is in general no better algorithm to solve this
      problem than exhaustively going through all N configurations of the system to
      determine the one with lowest energy, requiring a running time proportional to N.
      A quantum computer, if it could be built, could solve this problem in time
      sqrt[N]. Here, we present a powerful extension of this result to the case of
      interacting quantum particles, demonstrating that a quantum computer can prepare
      the ground state of a quantum system as efficiently as it does for classical
      systems.

PMID- 19392339
TI  - Aging and effective temperatures near a critical point.
AB  - The orientation fluctuations of the director of a liquid crystal are measured
      after a quench near the Freedericksz transition, which is a second order
      transition driven by an electric field. We report experimental evidence that,
      because of the critical slowing down, the liquid crystal presents several
      properties of an aging system after the quench, such as power law scaling in
      times of correlation and response functions. During this slow relaxation, a well
      defined effective temperature, much larger than the heat bath temperature, can be
      measured using the fluctuation dissipation relation.

PMID- 19392340
TI  - Universality of efficiency at maximum power.
AB  - We investigate the efficiency of power generation by thermochemical engines. For
      strong coupling between the particle and heat flows and in the presence of a left
      right symmetry in the system, we demonstrate that the efficiency at maximum power
      displays universality up to quadratic order in the deviation from equilibrium. A
      maser model is presented to illustrate our argument.

PMID- 19392341
TI  - Relaxation of antiferromagnetic order in spin-1/2 chains following a quantum
      quench.
AB  - We study the unitary time evolution of antiferromagnetic order in anisotropic
      Heisenberg chains that are initially prepared in a pure quantum state far from
      equilibrium. Our analysis indicates that the antiferromagnetic order imprinted in
      the initial state vanishes exponentially. Depending on the anisotropy parameter,
      oscillatory or nonoscillatory relaxation dynamics is observed. Furthermore, the
      corresponding relaxation time exhibits a minimum at the critical point, in
      contrast to the usual notion of critical slowing down, from which a maximum is
      expected.

PMID- 19392342
TI  - Steering Bose-Einstein condensates despite time symmetry.
AB  - A Bose-Einstein condensate in an oscillating spatially asymmetric potential is
      shown to exhibit a directed current for unbiased initial conditions despite time
      symmetry. This phenomenon occurs only if the interaction between atoms, treated
      in mean-field approximation, exceeds a critical value. Our findings can be
      described with a three-mode model. These three-mode model results corroborate
      well with a many-body study over a time scale which increases with increasing
      atom number. The duration of this time scale probes the validity of the used mean
      field approximation.

PMID- 19392343
TI  - Statistics of temperature fluctuations in an electron system out of equilibrium.
AB  - We study the statistics of the fluctuating electron temperature in a metallic
      island coupled to reservoirs via resistive contacts and driven out of equilibrium
      by either a temperature or voltage difference between the reservoirs. The
      fluctuations of temperature are well defined provided that the energy relaxation
      rate inside the island exceeds the rate of energy exchange with the reservoirs.
      We quantify these fluctuations in the regime beyond the Gaussian approximation
      and elucidate their dependence on the nature of the electronic contacts.

PMID- 19392344
TI  - Dynamics of quantum vorticity in a random potential.
AB  - I study the dynamics of a superfluid vortex in a random potential, as in the
      inner crust of a neutron star. Below a critical flow velocity of the ambient
      superfluid, a vortex is effectively immobilized by lattice forces even in the
      limit of zero dissipation. Low-velocity, translatory motion is not dynamically
      possible, a result with important implications for understanding neutron star
      precession and the dynamical properties of superfluid nuclear matter.

PMID- 19392345
TI  - Model-independent test for scale-dependent non-Gaussianities in the cosmic
      microwave background.
AB  - We present a model-independent method to test for scale-dependent non
      Gaussianities in combination with scaling indices as test statistics. Therefore,
      surrogate data sets are generated, in which the power spectrum of the original
      data is preserved, while the higher order correlations are partly randomized by
      applying a scale-dependent shuffling procedure to the Fourier phases. We apply
      this method to the Wilkinson Microwave Anisotropy Probe data of the cosmic
      microwave background and find signatures for non-Gaussianities on large scales.
      Further tests are required to elucidate the origin of the detected anomalies.

PMID- 19392346
TI  - Can stochastic quantization evade the sign problem? The relativistic bose gas at
      finite chemical potential.
AB  - A nonperturbative study of field theories with a complex action, such as QCD at
      finite baryon density, is difficult due to the sign problem. We show that the
      relativistic Bose gas at finite chemical potential has a sign and "silver blaze"
      problem, similar to QCD. We then apply stochastic quantization and complex
      Langevin dynamics to study this theory with nonperturbative lattice simulations.
      Independence of chemical potential at small and a transition to a condensed phase
      at large chemical potential are found. Lattices of size N4, with N=4, 6, 8, 10,
      are used. We show that the sign problem is severe, however, we find that it has
      no negative effect using this approach. This improves the prospects of applying
      stochastic quantization to QCD at nonzero density.

PMID- 19392348
TI  - Structure of Meson-Baryon interaction vertices.
AB  - We present a microscopic derivation of the form factors of strong-interaction
      piNN and piNDelta vertices within a relativistic constituent quark model. The
      results are compared with form factors from phenomenological meson-baryon models
      and recent lattice QCD calculations. We give an analytical representation of the
      vertex form factors suitable for applications in further studies of hadron
      reactions.

PMID- 19392349
TI  - rp process and masses of N approximately Z approximately 34 nuclides.
AB  - High-precision Penning-trap mass measurements of the N approximately Z
      approximately 34 nuclides 68Se, 70Se, (70m)Br, and 71Br were performed, reaching
      experimental uncertainties of 0.5-15 keV. The new and improved mass data together
      with theoretical Coulomb displacement energies were used as input for rp process
      network calculations. An increase in the effective lifetime of the waiting point
      nucleus 68Se was found, and more precise information was obtained on the
      luminosity during a type I x-ray burst along with the final elemental abundances
      after the burst.

PMID- 19392350
TI  - Two-nucleon knockout spectroscopy at the limits of nuclear stability.
AB  - Sudden single-nucleon removal reactions from fast radioactive beams are now key
      to studies of the structure of rare isotopes. The sensitivity of the heavy
      residue's parallel momentum distribution to the orbital angular momentum of the
      removed nucleon is a crucial feature with a high spectroscopic value. Two-nucleon
      removal reactions provide experimental reach toward the rarest nuclear species.
      We show that the residue parallel momentum distributions in these reactions offer
      a clear spectroscopic signal of the angular momentum of the pair of nucleons
      removed, and thus of the residue final state spins and spectroscopy. Our
      formalism is applied successfully to new final-state-inclusive measurements of
      like-nucleon pair removal reactions to states in neutron-rich 36Mg and neutron
      deficient 20Mg. We also confront a new final-state-exclusive decomposition of two
      proton knockout data to states in neutron-rich 26Ne.

PMID- 19392351
TI  - Efimov trimer formation via ultracold four-body recombination.
AB  - We discuss the collisional formation of Efimov trimers via ultracold four-body
      recombination. In particular, we consider the reaction A+A+A+B-->A_{3}+B with A
      and B ultracold atoms. We obtain expressions for the four-body recombination rate
      up to an overall constant and show that it reflects the three-body Efimov physics
      either as a function of collision energy or as a function of the two-body s-wave
      scattering length between A atoms. In addition, we briefly discuss issues
      important for experimentally observing this interesting and unexplored process.

PMID- 19392352
TI  - Excited-state positronium formation from helium, argon, and xenon.
AB  - The cross sections for the formation of positronium in the 2P state in collisions
      of positrons with He, Ar, and Xe atoms have been determined by measuring
      coincidences between the remnant ion and the Lyman-alpha photon from positronium.
      The maximum fractional contributions of these to the total Ps formation cross
      sections increase from approximately 0.06+/-0.01 in He to 0.12+/-0.04 in Ar and
      0.26+/-0.09 in Xe. In the case of He, good agreement is found with a coupled
      state calculation; for Ar and Xe, measurements are compared with a distorted-wave
      Born approximation.

PMID- 19392353
TI  - All-dielectric rod-type metamaterials at optical frequencies.
AB  - Light propagation in all-dielectric rod-type metamaterials is studied
      theoretically. The electric and magnetic dipole moments of the rods are derived
      analytically in the long-wavelength limit. The effective permittivity and
      permeability of a square lattice of rods are calculated by homogenizing the
      corresponding array of dipoles. The role of dipole resonances in the optical
      properties of the rod array is interpreted. This structure is found to exhibit a
      true left-handed behavior, confirming previous experiments [L. Peng, Phys. Rev.
      Lett. 98, 157403 (2007)10.1103/PhysRevLett.98.157403]. A scaling analysis shows
      that this effect holds at optical frequencies and can be obtained by using rods
      made, for example, of silicon.

PMID- 19392354
TI  - Self-collimation of light over millimeter-scale distance in a quasi-zero-average
      index metamaterial.
AB  - Inspired by the concept of complementary media, we experimentally demonstrate
      that an engineered metamaterial made of alternating, stripe layers of negatively
      refracting (photonic crystals) and positively refracting (air) materials strongly
      collimates a beam of near-infrared light. This quasi-zero-average-index
      metamaterial fully preserves the beam spot size throughout the sample for a light
      beam traveling through the metamaterial a distance of 2 mm-more than 1000 times
      the input wavelength lambda=1.55 microm. These results demonstrate the first
      explicit experimental verification of optical antimatter as proposed by Pendry
      and Ramakrishna [J. Pendry and S. Ramakrishna, J. Phys. Condens. Matter 15, 6345
      (2003)10.1088/0953-8984/15/37/004], using two complementary media in which each
      n(eff)=-1 layer appears to annihilate an equal thickness layer of air.

PMID- 19392355
TI  - Power-dependent reflection, transmission, and trapping dynamics of lattice
      solitons at interfaces.
AB  - Surface soliton formation and lattice soliton dynamics at an interface between
      two inhomogeneous periodic media are studied in terms of an effective particle
      approach. The global reflection, transmission, and trapping characteristics are
      obtained in direct analogy to linear Snell's laws for homogeneous media.
      Interesting dynamics related to soliton power-dependent formation of potential
      barriers and wells suggest a spatial filtering functionality of the respective
      structures.

PMID- 19392356
TI  - Oscillatory neck instability of spatial bright solitons in hyperbolic systems.
AB  - The breakup of spatial bright optical solitons due to oscillatory neck
      instability is experimentally studied by propagating a laser beam in normally
      dispersive and self-focusing Kerr media. This intriguing and unusual phenomenon,
      recently predicted for solitons of the (2+1)-dimensional hyperbolic nonlinear
      Schrodinger (NLS) equation, is observed in the spatially resolved temporal
      spectrum. The snake instability that is known to occur in hyperbolic systems is
      also demonstrated to validate our experimental approach. Our results not only
      apply to photonics but also to other fields of physics, such as hydrodynamics or
      plasma physics, in which the hyperbolic NLS equation is used as a canonical
      model.

PMID- 19392357
TI  - Shifted feedback suppression of turbulent behavior in advection-diffusion
      systems.
AB  - In spatiotemporal systems with advection, suppression of noise-sustained
      structures involves questions that are outside of the framework of deterministic
      dynamical systems control (such as Ott-Grebogi-Yorke-type methods). Here we
      propose and test an alternate strategy where a nonlocal additive feedback is
      applied, with the objective to create a new deterministic solution that becomes
      robust to noise. As a remarkable fact-though the needed parameter perturbations
      required have essentially a finite size-they turn out to be extraordinarily small
      in principle: 10;{-8} in the free-electron laser experiment presented here.

PMID- 19392358
TI  - Precursors to splashing of liquid droplets on a solid surface.
AB  - A high velocity impact between a liquid droplet and a solid surface produces a
      splash. Classical work traced the origin of the splash to a thin sheet of fluid
      ejected near the impact point. Mechanisms of sheet formation have heretofore
      relied on initial contact of the droplet and the surface. We demonstrate that,
      neglecting intermolecular forces between the liquid and the solid, the liquid
      does not contact the solid, and instead spreads on a very thin air film. The
      interface of the droplet develops a high curvature and emits capillary waves.

PMID- 19392359
TI  - New flow regimes generated by mode coupling in buoyant-thermocapillary
      convection.
AB  - We report on a new nonlinear dynamics occurring in a confined cylindrical column
      filled with fluid (liquid bridge) and heated from above. We demonstrate and
      analyze the novel oscillatory flow state created by the interaction of two
      hydrothermal waves of different origins: one propagates vertically from the cold
      towards the hot side (m=0) and another is traveling in the azimuthal direction
      (m=1). Their interaction leads to an exotic flow structure: during a part of the
      oscillation period the resulting wave propagates in a given azimuthal direction,
      whereas during the rest of the period it moves in the opposite direction. A new
      bimodal flow regime is found to exist over a parameter range where these modes
      have comparable influence. The phase diagrams, obtained by three-dimensional
      nonlinear simulations, are reported. They shed light on the instability mechanism
      and criteria of the existence of novel states.

PMID- 19392347
TI  - Evidence for X(3872)-->psi(2S)gamma in B(+/-)-->X(3872)K(+/-) decays and a study
      of B-->cc[over ]gammaK.
AB  - In a search for B-->cc[over ]gammaK decays with the BABAR detector, where cc[over
      ] includes J/psi and psi(2S), and K includes K(+/-), K(S)(0), and K(*)(892), we
      find evidence for X(3872)-->J/psigamma and X(3872)-->psi(2S)gamma with 3.6sigma
      and 3.5sigma significance, respectively. We measure the product of branching
      fractions B(B(+/-)-->X(3872)K(+/-))xB(X(3872)-->J/psigamma)=[2.8+/-0.8(stat)+/
      0.1(syst)]x10(-6) and B(B(+/-)-->X(3872)K(+/-))xB(X(3872)-->psi(2S)gamma)=[9.5+/
      2.7(stat)+/-0.6(syst)]x10(-6).

PMID- 19392360
TI  - Fluid mixing in stratified gravity currents: the Prandtl mixing length.
AB  - Shear-induced vertical mixing in a stratified flow is a key ingredient of
      thermohaline circulation. We experimentally determine the vertical flux of
      momentum and density of a forced gravity current using high-resolution velocity
      and density measurements. A constant eddy-viscosity model provides a poor
      description of the physics of mixing, but a Prandtl mixing length model relating
      momentum and density fluxes to mean velocity and density gradients works well.
      For the average gradient Richardson number Ri(g) approximately 0.08 and a Taylor
      Reynolds number Re(lambda) approximately 100, the mixing lengths are fairly
      constant, about the same magnitude, comparable to the turbulent shear length.

PMID- 19392361
TI  - Dynamical model for the buoyancy-driven zigzag motion of oblate bodies.
AB  - We describe a dynamical model that predicts the zigzag motion of disks and oblate
      spheroids moving freely in a viscous liquid over a continuous range of aspect
      ratios and Reynolds numbers. This model combines the generalized Kirchhoff
      equations to describe the linear and angular momentum balances for the fluid-body
      system with a dynamical model for the wake-induced force and torque that
      incorporates the main characteristics of the wake dynamics deduced from previous
      experimental observations. The resulting model is shown to be able to reproduce
      quantitatively the oscillatory paths measured experimentally.

PMID- 19392362
TI  - Kinetic effects of energetic particles on resistive MHD stability.
AB  - We show that the kinetic effects of energetic particles can play a crucial role
      in the stability of the m/n=2/1 tearing mode in tokamaks (e.g., JET, JT-60U, and
      DIII-D), where the fraction of energetic particle beta(frac) is high. Using model
      equilibria based on DIII-D experimental reconstructions, the nonideal MHD linear
      stability of cases unstable to the 2/1 mode is investigated including a deltaf
      particle-in-cell model for the energetic particles coupled to the nonlinear 3D
      resistive MHD code NIMROD [C. C. Kim et al., Phys. Plasmas 15, 072507
      (2008)10.1063/1.2949704]. It is observed that energetic particles have
      significant damping and stabilizing effects at experimentally relevant beta,
      beta(frac), and S, and excite a real frequency of the 2/1 mode. Extrapolation of
      the results is discussed for implications to JET and ITER, where the effects are
      projected to be significant.

PMID- 19392363
TI  - Dissipative dark soliton in a complex plasma.
AB  - The observation of a dark soliton in a three-dimensional complex plasma
      containing monodisperse microparticles is presented. We perform our experiments
      using neon gas in the bulk plasma of an rf discharge. A gas temperature gradient
      of 500K/m is applied to balance gravity and to levitate the particles in the bulk
      plasma. The wave is excited by a short voltage pulse on the electrodes of the
      radio frequency discharge chamber. It is found that the wave propagates with
      constant speed. The propagation time of the dark soliton is approximately 20
      times longer than the damping time.

PMID- 19392364
TI  - One-dimensional Vlasov-Maxwell equilibrium for the force-free Harris sheet.
AB  - In this Letter, the first nonlinear force-free Vlasov-Maxwell equilibrium is
      presented. One component of the equilibrium magnetic field has the same spatial
      structure as the Harris sheet, but whereas the Harris sheet is kept in force
      balance by pressure gradients, in the force-free solution presented here force
      balance is maintained by magnetic shear. Magnetic pressure, plasma pressure and
      plasma density are constant. The method used to find the equilibrium is based on
      the analogy of the one-dimensional Vlasov-Maxwell equilibrium problem to the
      motion of a pseudoparticle in a two-dimensional conservative potential. The force
      free solution can be generalized to a complete family of equilibria that describe
      the transition between the purely pressure-balanced Harris sheet to the force
      free Harris sheet.

PMID- 19392365
TI  - Polaritons and pairing phenomena in Bose-Hubbard mixtures.
AB  - Motivated by recent experiments on cold atomic gases in ultrahigh finesse optical
      cavities, we consider the two-band Bose-Hubbard model coupled to quantum light.
      Photoexcitation promotes carriers between the bands, and we study the interplay
      between Mott insulating behavior and superfluidity. The model displays a
      U(1)xU(1) symmetry which supports the coexistence of Mott insulating and
      superfluid phases and yields a rich phase diagram with multicritical points. This
      symmetry is shared by several other problems of current experimental interest,
      including two-component Bose gases in optical lattices and the bosonic BEC-BCS
      crossover for atom-molecule mixtures induced by a Feshbach resonance. We
      corroborate our findings by numerical simulations.

PMID- 19392366
TI  - Discerning incompressible and compressible phases of cold atoms in optical
      lattices.
AB  - Experiments with cold atoms trapped in optical lattices offer the potential to
      realize a variety of novel phases but suffer from severe spatial inhomogeneity
      that can obscure signatures of new phases of matter and phase boundaries. We use
      a high temperature series expansion to show that compressibility in the core of a
      trapped Fermi-Hubbard system is related to measurements of changes in double
      occupancy. This core compressibility filters out edge effects, offering a direct
      probe of compressibility independent of inhomogeneity. A comparison with
      experiments is made.

PMID- 19392367
TI  - Symmetry breaking of graphene monolayers by molecular decoration.
AB  - Aromatic molecules can effectively exfoliate graphite into graphene monolayers,
      and the resulting graphene monolayers sandwiched by the aromatic molecules
      exhibit a pronounced Raman G-band splitting, similar to that observed in single
      walled carbon nanotubes. Raman measurements and calculations based on the force
      constant model demonstrate that the absorbed aromatic molecules are responsible
      for the G-band splitting by removing the energy degeneracy of in-plane
      longitudinal and transverse optical phonons at the Gamma point.

PMID- 19392368
TI  - Resonant interaction between hydrogen vibrational modes in AlSb:Se.
AB  - Vibrational modes and their interactions affect numerous physical processes in
      condensed-matter systems. In the present work, hydrogen vibrations in Se-doped
      AlSb were investigated with first-principles calculations. Vibrational
      frequencies were calculated for the longitudinal, transverse, wag (bending), and
      stretch modes of the Al-H complex. The Al-H stretch mode interacts with a
      combination mode involving a wag overtone and transverse fundamental. This
      resonant interaction yields vibrational states that are linear superpositions of
      the stretch mode and the combination mode. The spatial extent of such excitations
      is significantly larger than that of a local vibrational mode.

PMID- 19392369
TI  - Fluctuation dissipation relations in stationary states of interacting Brownian
      particles under shear.
AB  - The fluctuation dissipation theorem is studied close to the glass transition in
      colloidal suspensions under steady shear. Shear breaks detailed balance in the
      many-particle Smoluchowski equation and gives response functions in the
      stationary state which are smaller at long times than estimated from the
      equilibrium fluctuation dissipation theorem. During the final shear-driven decay,
      an asymptotically constant relation connects response and fluctuations, restoring
      the form of the fluctuation dissipation theorem with, however, a ratio different
      from the equilibrium one.

PMID- 19392370
TI  - Topology-induced anomalous defect production by crossing a quantum critical
      point.
AB  - We study the influence of topology on the quench dynamics of a system driven
      across a quantum critical point. We show how the appearance of certain edge
      states, which fully characterize the topology of the system, dramatically
      modifies the process of defect production during the crossing of the critical
      point. Interestingly enough, the density of defects is no longer described by the
      Kibble-Zurek scaling, but determined instead by the nonuniversal topological
      features of the system. Edge states are shown to be robust against defect
      production, which highlights their topological nature.

PMID- 19392371
TI  - Observation of surface self-diffusion on ice.
AB  - To determine the role of surface diffusion on the morphology of ice surfaces we
      track the evolution with STM of 2D ice-island arrays on the basal surface of ice
      films on Pt(111) between 115 and 135 K. In contrast with previous measurements at
      higher temperatures, we find that the evolution is dominated by surface
      diffusion. The extracted surface self-diffusion coefficient has an activation
      energy of 0.4+/-0.1 eV, much less than the value previously measured for bulk
      diffusion.

PMID- 19392372
TI  - Temperature-induced enhancement of nanoscale friction.
AB  - We introduce a novel mechanism of temperature dependence of friction at the
      nanoscale which is determined by a decrease of the slip length with temperature
      T. We find that the effect of temperature on the slip length may result in a rich
      temperature dependence of friction, including a peak and/or plateau in F as a
      function of T, and a sharp increase or decrease of F with T. This mechanism is of
      primary importance in the multiple-slip regimes of motion when the tip slips over
      a number of lattice spacings. The influence of normal load and driving velocity
      on the temperature dependence of friction is discussed. We predict that the
      presence of surface defects or adsorbate may strongly influence the temperature
      dependence of friction.

PMID- 19392373
TI  - Imaging of the hydrogen subsurface site in rutile TiO2.
AB  - From an interplay between simultaneously recorded noncontact atomic force
      microscopy and scanning tunneling microscopy images and simulations based on
      density functional theory, we reveal the location of single hydrogen species in
      the surface and subsurface layers of rutile TiO2. Subsurface hydrogen atoms
      (H(sub)) are found to reside in a stable interstitial site as subsurface OH
      groups detectable in scanning tunneling microscopy as a characteristic electronic
      state but imperceptible to atomic force microscopy. The combined atomic force
      microscopy, scanning tunneling microscopy, and density functional theory study
      demonstrates a general scheme to reveal near surface defects and interstitials in
      poorly conducting materials.

PMID- 19392374
TI  - Magic-sized diamond nanocrystals.
AB  - The 2D structural transformation of a heavily boron-doped diamond surface has
      been revealed using scanning tunneling microscopy (STM). We found that at boron
      densities above the metal-insulator transition the diamond surface is comprised
      of spatially ordered magic-sized nanocrystals. The development of quantized
      electron gas inside these nanocrystals is directly confirmed by STM observation
      of standing electron waves. The experimental comparison of metallic and
      insulating diamond reveals the existence of the Fermi-sea-induced quantum
      selection rules for the self-assembly of nanostructures.

PMID- 19392375
TI  - Interface structures of gold nanoparticles on TiO2 (110).
AB  - Scanning transmission electron microscopy and density functional theory are used
      to characterize atomic structures of nanoscale heterointerfaces between gold
      nanoparticles and a TiO2 (110) surface. It is found that when the gold
      nanoparticle size is smaller than a few nanometers, gold atoms preferentially
      attach to specific sites on the TiO2 surface and thus form an epitaxial and
      coherent heterointerface. Conversely, as the gold size becomes larger, the gold
      TiO2 interface loses lattice coherency in order to accommodate the large lattice
      mismatch between the two dissimilar crystals.

PMID- 19392376
TI  - Theoretical description of time-resolved photoemission spectroscopy: application
      to pump-probe experiments.
AB  - The theory for time-resolved, pump-probe, photoemission spectroscopy and other
      pump-probe experiments is developed. The formal development is completely
      general, incorporating all of the nonequilibrium effects of the pump pulse and
      the finite time width of the probe pulse, and including possibilities for taking
      into account band structure and matrix element effects, surface states, and the
      interaction of the photoexcited electrons with the system leading to corrections
      to the sudden approximation. We also illustrate the effects of windowing that
      arise from the finite width of the probe pulse in a simple model system by
      assuming the quasiequilibrium approximation.

PMID- 19392377
TI  - Large electric field effect in electrolyte-gated manganites.
AB  - We have studied electrostatic field-induced doping in La0.8Ca0.2MnO3 transistors
      using electrolyte as a gate dielectric. For positive gate bias, electron doping
      drives a transition from a ferromagnetic metal to an insulating ground state. The
      thickness of the electrostatically doped layer depends on bias voltage but can
      extend to 5 nm requiring a field doping of 2x10;{15} charges per cm;{2}
      equivalent to 2.5 electrons per unit cell area. In contrast, negative gate
      voltages enhance the metallic conductivity by 30%.

PMID- 19392378
TI  - Stimulated scattering and lasing of intersubband cavity polaritons.
AB  - We present a microscopic theory describing the stimulated scattering of
      intersubband polariton excitations in a microcavity-embedded two-dimensional
      electron gas. In particular, we consider the polariton scattering induced by the
      interaction with longitudinal optical phonons. Our theory demonstrates the
      possibility of final-state stimulation for the scattering of such composite
      excitations, accounting for the deviations from ideal bosonicity occurring at
      high excitation densities. By using GaAs parameters, we predict a quantum
      degenerate regime and lasing without electronic population inversion in an
      optical pumping configuration.

PMID- 19392379
TI  - Inhomogeneous magnetic phases: a Fulde-Ferrell-Larkin-Ovchinnikov-like phase in
      Sr3Ru2O7.
AB  - The phase diagram of Sr3Ru2O7 contains a metamagnetic transition that bifurcates
      to enclose an anomalous phase with intriguing properties--a large resistivity
      with anisotropy that breaks the crystal-lattice symmetry. We propose that this is
      a magnetic analogue of the spatially inhomogeneous superconducting Fulde-Ferrel
      Larkin-Ovchinnikov state. We show-through a Ginzburg-Landau expansion where the
      magnetization transverse to the applied field can become spatially inhomogeneous
      that a Stoner model with electronic band dispersion can reproduce this phase
      diagram and transport behavior.

PMID- 19392380
TI  - Correlated electrons in Fe-As compounds: a quantum chemical perspective.
AB  - State-of-the-art quantum chemical methods are applied to the study of the
      multiorbital correlated electronic structure of a Fe-As compound, the recently
      discovered LiFeAs. Our calculations predict a high-spin, S=2, ground-state
      configuration for the Fe ions, which shows that the on-site Coulomb interactions
      are substantial. Also, orbital degeneracy in the (xz, yz) sector and a three
      quarter filling of these levels suggest the presence of strong fluctuations and
      are compatible with a low metallic conductivity in the normal state. The lowest
      electron-removal states have As 4p character, in analogy with the ligand hole
      states in p-type cuprate superconductors.

PMID- 19392381
TI  - Observation of exciton-phonon sideband in individual metallic single-walled
      carbon nanotubes.
AB  - Single-walled carbon nanotubes (SWCNTs) are quasi-one-dimensional systems with
      poor Coulomb screening and enhanced electron-phonon interaction, and are good
      candidates for excitons and exciton-phonon couplings in metallic state. Here we
      report backscattering reflection experiments on individual metallic SWCNTs. An
      exciton-phonon sideband separated by 0.19 eV from the first optical transition
      peak is observed in a metallic SWCNT of chiral index (13,10), which provides
      clear evidences of excitons in metallic SWCNTs. A static dielectric constant of
      10 is estimated from the reflectance spectrum.

PMID- 19392382
TI  - Emergence of a diffusive metal state with no magnetic order near the Mott
      transition in frustrated pyrochlore-type molybdates.
AB  - The electron-correlation driven metal-insulator (Mott) transition in pyrocholore
      type R2Mo2O7(R being rare-earth-metal ions) is accompanied by the change of the
      magnetic state from ferromagnetic to spin glass due to the competing double
      exchange and superexchange interactions on the frustrated lattice. By application
      of high pressures on the compounds with Mott criticality, however, a new unique
      paramagnetic metal phase is observed to show up with nearly temperature
      independent high resistivity close to the Ioffe-Regel limit. A possible non-Fermi
      liquid character of this anomalously diffuse metallic state is argued in terms of
      the extended double-exchange model with the magnetically frustrated local S=1/2
      spins.

PMID- 19392383
TI  - Morphology of the superconducting vortex lattice in ultrapure niobium.
AB  - The morphology of the superconducting flux line lattice (FLL) of Nb comprises
      gradual variations with various lock-in transitions and symmetry breaking
      rotations. We report a comprehensive small-angle neutron scattering study of the
      FLL in an ultrapure single crystal of Nb as a function of the orientation of the
      applied magnetic field. We attribute the general morphology of the FLL and its
      orientation to three dominant mechanisms; first, nonlocal contributions, second,
      the transition between open and closed Fermi surface sheets and, third, the
      intermediate mixed state between the Meissner and the Shubnikov phase.

PMID- 19392384
TI  - Bright and grey states in CdSe-CdS nanocrystals exhibiting strongly reduced
      blinking.
AB  - When compared to standard colloidal nanocrystals, individual CdSe-CdS core-shell
      nanocrystals with thick shells exhibit strongly reduced blinking. Analyzing the
      photon statistics and lifetime of the on state, we first demonstrate that bright
      periods correspond to single photon emission with a fluorescence quantum
      efficiency of the monoexcitonic state greater than 95%. We also show that low
      intensity emitting periods are not dark but correspond to a grey state, with a
      fluorescence quantum efficiency of 19%. From these measurements, we deduce the
      radiative lifetime (45 ns) and the Auger lifetime (10.5 ns) of the grey state.

PMID- 19392385
TI  - Persistent currents in normal metal rings.
AB  - The authors have measured the magnetic response of 33 individual cold mesoscopic
      gold rings, one ring at a time. The response of some sufficiently small rings has
      a component that is periodic in the flux through the ring and is attributed to a
      persistent current. Its period is close to h/e, and its sign and amplitude vary
      between rings. The amplitude distribution agrees well with predictions for the
      typical h/e current in diffusive rings. The temperature dependence of the
      amplitude, measured for four rings, is also consistent with theory. These results
      disagree with previous measurements of three individual metal rings that showed a
      much larger periodic response than expected. The use of a scanning SQUID
      microscope enabled in situ measurements of the sensor background. A paramagnetic
      linear susceptibility and a poorly understood anomaly around a zero field are
      attributed to defect spins.

PMID- 19392386
TI  - Coherent electronic transport through graphene constrictions: subwavelength
      regime and optical analogy.
AB  - Nanoelectronic devices smaller than the electron wavelength can be achieved in
      graphene with current lithography techniques. Here we show that the electronic
      quantum transport of graphene subwavelength nanodevices presents deep analogies
      with subwavelength optics. We introduce the concept of electronic diffraction
      barrier to represent the effect of constrictions and the rich transport phenomena
      of a variety of nanodevices. Results are presented for Bethe and Kirchhoff
      diffraction in graphene slits and Fabry-Perot interference oscillations in
      nanoribbons. The same concept applies to graphene quantum dots and gives new
      insight into recent experiments in these systems.

PMID- 19392387
TI  - Pinning mode resonances of 2D electron stripe phases: effect of an in-plane
      magnetic field.
AB  - We study the anisotropic pinning-mode resonances in the rf conductivity spectra
      of the stripe phase of 2D electron systems around a Landau level filling of 9/2,
      in the presence of an in-plane magnetic field B(ip). The polarization along which
      the resonance is observed switches as B(ip) is applied, consistent with the
      reorientation of the stripes. The resonance frequency, a measure of the pinning
      interaction between the 2D electron systems and disorder, increases with B(ip).
      The magnitude of this increase indicates that disorder interaction is playing an
      important role in determining the stripe orientation.

PMID- 19392388
TI  - Quantum criticality perspective on the charging of narrow quantum-dot levels.
AB  - Understanding the charging of exceptionally narrow levels in quantum dots in the
      presence of interactions remains a challenge within mesoscopic physics. We
      address this fundamental question in the generic model of a narrow level
      capacitively coupled to a broad one. Using bosonization we show that for
      arbitrary capacitive coupling charging can be described by an analogy to the
      magnetization in the anisotropic Kondo model, featuring a low-energy crossover
      scale that depends in a power-law fashion on the tunneling amplitude to the
      level. Explicit analytical expressions for the exponent are derived and confirmed
      by detailed numerical and functional renormalization-group calculations.

PMID- 19392389
TI  - Topological Anderson insulator.
AB  - Disorder plays an important role in two dimensions, and is responsible for
      striking phenomena such as metal-insulator transition and the integral and
      fractional quantum Hall effects. In this Letter, we investigate the role of
      disorder in the context of the recently discovered topological insulator, which
      possesses a pair of helical edge states with opposing spins moving in opposite
      directions and exhibits the phenomenon of quantum spin Hall effect. We predict an
      unexpected and nontrivial quantum phase termed "topological Anderson insulator,"
      which is obtained by introducing impurities in a two-dimensional metal; here
      disorder not only causes metal-insulator transition, as anticipated, but is
      fundamentally responsible for creating extended edge states. We determine the
      phase diagram of the topological Anderson insulator and outline its experimental
      consequences.

PMID- 19392390
TI  - Conservation of the lateral electron momentum at a metal-semiconductor interface
      studied by ballistic electron emission microscopy.
AB  - We report on ballistic electron emission microscopy and spectroscopy studies on
      epitaxial (3-5 nm thick) Bi(111) films, grown on n-type Si substrates. The
      effective barrier heights of the Schottky barrier observed are 0.58 eV for the
      Bi/Si(100)-(2x1) and 0.68 eV for the Bi/Si(111)-(7x7). At the step edges of the
      epitaxial films a strong increase of the ballistic electron emission microscopy
      current is observed for Bi/Si(111)-(7x7), while no increase occurs for Bi/Si(100)
      (2x1). These observations can be explained by the conservation of the lateral
      momentum of the electron at the metal-semiconductor interface.

PMID- 19392391
TI  - High-mobility few-layer graphene field effect transistors fabricated on epitaxial
      ferroelectric gate oxides.
AB  - The carrier mobility mu of few-layer graphene (FLG) field-effect transistors
      increases tenfold when the SiO2 substrate is replaced by single-crystal epitaxial
      Pb(Zr0.2Ti0.8)O3 (PZT). In the electron-only regime of the FLG, mu reaches
      7x10(4) cm(2)/V s at 300 K for n=2.4x10(12)/cm(2), 70% of the intrinsic limit set
      by longitudinal acoustic (LA) phonons; it increases to 1.4x10(5) cm(2)/V s at low
      temperature. The temperature-dependent resistivity rho(T) reveals a clear
      signature of LA phonon scattering, yielding a deformation potential D=7.8+/-0.5
      eV.

PMID- 19392392
TI  - Chemical versus van der Waals Interaction: the role of the heteroatom in the flat
      absorption of aromatic molecules C6H6, C5NH5, and C4N2H4 on the Cu(110) surface.
AB  - We perform first-principles calculations aimed at investigating the role of a
      heteroatom such as N in the chemical and long-range van der Waals (vdW)
      interactions for a flat adsorption of several pi-conjugated molecules on the
      Cu(110) surface. Our study reveals that the alignment of the molecular orbitals
      at the adsorbate-substrate interface depends on the number of heteroatoms. As a
      direct consequence, the molecule-surface vdW interactions involve not only pi
      like orbitals which are perpendicular to the molecular plane but also sigma-like
      orbitals delocalized in the molecular plane.

PMID- 19392393
TI  - Giant magnetoresistance in ultrasmall graphene based devices.
AB  - By computing spin-polarized electronic transport across a finite zigzag graphene
      ribbon bridging two metallic graphene electrodes, we demonstrate, as a proof of
      principle, that devices featuring 100% magnetoresistance can be built entirely
      out of carbon. In the ground state a short zigzag ribbon is an antiferromagnetic
      insulator which, when connecting two metallic electrodes, acts as a tunnel
      barrier that suppresses the conductance. The application of a magnetic field
      makes the ribbon ferromagnetic and conductive, increasing dramatically the
      current between electrodes. We predict large magnetoresistance in this system at
      liquid nitrogen temperature and 10 T or at liquid helium temperature and 300 G.

PMID- 19392394
TI  - Electron-spin dynamics in strongly correlated metals.
AB  - The temperature dependence of the electron-spin lifetime T1 and the g factor are
      anomalous in alkali fullerides (K,Rb)3C60, which cannot be explained by the
      canonical Elliott-Yafet theory. These materials are archetypes of strongly
      correlated and narrow band metals. We introduce the concept of a "complex
      electron-spin resonance frequency shift" to treat these measurables in a unified
      manner within the Kubo formalism. The theory is applicable for metals with nearly
      degenerate conduction bands and large momentum scattering even with an anomalous
      temperature dependence and sizable residual value.

PMID- 19392395
TI  - Superconductivity induced by phosphorus doping and its coexistence with
      ferromagnetism in EuFe2(As0.7P0.3)(2).
AB  - We have studied EuFe2(As0.7P0.3)(2) by the measurements of x-ray diffraction,
      electrical resistivity, thermopower, magnetic susceptibility, magnetoresistance,
      and specific heat. Partial substitution of As with P results in the shrinkage of
      lattice, which generates chemical pressure to the system. It is found that
      EuFe2(As0.7P0.3)(2) undergoes a superconducting transition at 26 K, followed by
      ferromagnetic ordering of Eu2+ moments at 20 K. This finding is the first
      observation of superconductivity stabilized by internal chemical pressure, and
      supplies a rare example showing the coexistence of superconductivity and
      ferromagnetism in the ferroarsenide family.

PMID- 19392396
TI  - Formula for the critical temperature of superconductors based on the electronic
      density of states and the effective mass.
AB  - A formula for the superconducting transition temperature T(c) is developed by
      comparing the total condensation energy contained within the coherence volume of
      a Cooper pair to the number of electronic states at the Fermi surface within the
      same coherence volume. It is found that T(c) is proportional to the ratio of the
      condensation energy density and normal state charge carrier density. We find that
      this relation holds for over 2 orders of magnitude in temperature for numerous
      well-known superconducting compounds belonging to distinctly different classes.

PMID- 19392397
TI  - Quantum stabilization of the 1/3-magnetization plateau in Cs2CuBr4.
AB  - We consider the phase diagram of a spatially anisotropic 2D triangular
      antiferromagnet in a magnetic field. Classically, the ground state is
      umbrellalike for all fields, but we show that the quantum phase diagram is much
      richer and contains a 1/3-magnetization plateau, two commensurate planar states,
      two incommensurate chiral umbrella phases, and, possibly, a spin density wave
      state separating the two chiral phases. Our analysis sheds light on several
      recent experimental findings for Cs2CuBr4.

PMID- 19392398
TI  - Domain wall spin torquemeter.
AB  - We report the direct measurement of the nonadiabatic component of the spin torque
      in domain walls. Our method is independent of both the pinning of the domain wall
      in the wire as well as of the Gilbert damping parameter. We demonstrate that the
      ratio between the nonadiabatic and the adiabatic components can be as high as 1,
      and explain this high value by the importance of the spin-flip rate to the
      nonadiabatic torque. In addition to their fundamental significance these results
      open the way for applications by demonstrating a significant increase of the spin
      torque efficiency.

PMID- 19392399
TI  - Scaling theory of magnetoresistance and carrier localization in Ga1-xMnxAs.
AB  - We compare experimental resistivity data on Ga1-xMnxAs films with theoretical
      calculations using a scaling theory for strongly disordered ferromagnets. The
      characteristic features of the temperature dependent resistivity can be
      quantitatively understood through this approach as originating from the close
      vicinity of the metal-insulator transition. However, accounting for thermal
      fluctuations is crucial for a quantitative description of the magnetic field
      induced changes in resistance. While the noninteracting scaling theory is in
      reasonable agreement with the data, we find clear evidence for interaction
      effects at low temperatures.

PMID- 19392400
TI  - Ferromagnetism and electronic structures of nonstoichiometric Heusler-alloy Fe3
      xMnxSi Epilayers grown on Ge(111).
AB  - For the study of ferromagnetic materials which are compatible with group-IV
      semiconductor spintronics, we demonstrate control of the ferromagnetic properties
      of Heusler-alloy Fe3-xMnxSi epitaxially grown on Ge(111) by tuning the Mn
      composition x. Interestingly, we obtain L2(1)-ordered structures even for
      nonstoichiometric atomic compositions. The Curie temperature of the epilayers
      with x approximately 0.6 exceeds 300 K. Theoretical calculations indicate that
      the electronic structures of the nonstoichiometric Fe3-xMnxSi alloys become half
      metallic for 0.75 < or = x < or = 1.5. We discuss the possibility of room
      temperature ferromagnetic Fe(3-x)Mn(x)Si/Ge epilayers with high spin
      polarization.

PMID- 19392401
TI  - Electron-hole asymmetry of spin injection and transport in single-layer graphene.
AB  - Spin-dependent properties of single-layer graphene (SLG) have been studied by
      nonlocal spin valve measurements at room temperature. Gate voltage dependence
      shows that the nonlocal magnetoresistance (MR) is proportional to the
      conductivity of the SLG, which is the predicted behavior for transparent
      ferromagnetic-nonmagnetic contacts. While the electron and hole bands in SLG are
      symmetric, gate voltage and bias dependence of the nonlocal MR reveal an electron
      hole asymmetry in which the nonlocal MR is roughly independent of bias for
      electrons, but varies significantly with bias for holes.

PMID- 19392402
TI  - Highly sensitive determination of the polaron-induced optical absorption of
      organic charge-transport materials.
AB  - We examine polaron-induced absorption in organic transport materials using a
      highly sensitive measurement technique. A hole only device is embedded into a low
      loss TE2 waveguide structure, and the current induced change of the waveguide
      absorption is measured. The exemplary study of 2,2('),7,7(')-tetrakis(N,N
      diphenylamine)-9,9(')-spiro-bifluorene (S-TAD) reveals a very low polaron
      absorption cross section of sigma(p) < or = 2.6 x 10(-18) cm(2) for 560 nm < or =
      lambda < or = 660 nm. The accuracy of this data is unsurpassed by other
      techniques used for the unambiguous study of polaronic species in organic thin
      films.

PMID- 19392403
TI  - Origin of intrinsic Gilbert damping.
AB  - The damping of magnetization, represented by the rate at which it relaxes to
      equilibrium, is successfully modeled as a phenomenological extension in the
      Landau-Lifschitz-Gilbert equation. This is the damping torque term known as
      Gilbert damping and its direction is given by the vector product of the
      magnetization and its time derivative. Here we derive the Gilbert term from first
      principles by a nonrelativistic expansion of the Dirac equation. We find that
      this term arises when one calculates the time evolution of the spin observable in
      the presence of the full spin-orbital coupling terms, while recognizing the
      relationship between the curl of the electric field and the time-varying magnetic
      induction.

PMID- 19392404
TI  - Critical scaling and aging in cooling systems near the jamming transition.
AB  - We conduct athermal simulations of freely cooling, viscous soft spheres around
      the jamming transition density varphi(J) and find evidence for a growing length
      xi(t) that governs relaxation to mechanical equilibrium. xi(t) is manifest in
      both the velocity correlation function and the spatial correlations in a scalar
      measure of local force balance which we define. Data for different densities
      varphi can be collapsed onto two master curves by scaling xi(t) and t by powers
      of |varphi-varphi(J)|, indicative of critical scaling. Furthermore, particle
      transport for varphi>varphi(J) exhibits aging and superdiffusion similar to a
      range of soft matter experiments, suggesting a common origin. Finally, we explain
      how xi(t) at late times maps onto known behavior away from varphi(J).

PMID- 19392405
TI  - Prediction of spatiotemporal patterns of neural activity from pairwise
      correlations.
AB  - We designed a model-based analysis to predict the occurrence of population
      patterns in distributed spiking activity. Using a maximum entropy principle with
      a Markovian assumption, we obtain a model that accounts for both spatial and
      temporal pairwise correlations among neurons. This model is tested on data
      generated with a Glauber spin-glass system and is shown to correctly predict the
      occurrence probabilities of spatiotemporal patterns significantly better than
      Ising models only based on spatial correlations. This increase of predictability
      was also observed on experimental data recorded in parietal cortex during slow
      wave sleep. This approach can also be used to generate surrogates that reproduce
      the spatial and temporal correlations of a given data set.

PMID- 19392406
TI  - Hybrid elastic and discrete-particle approach to biomembrane dynamics with
      application to the mobility of curved integral membrane proteins.
AB  - We introduce a simulation strategy to consistently couple continuum biomembrane
      dynamics to the motion of discrete biological macromolecules residing within or
      on the membrane. The methodology is used to study the diffusion of integral
      membrane proteins that impart a curvature on the bilayer surrounding them. Such
      proteins exhibit a substantial reduction in diffusion coefficient relative to
      "flat" proteins; this effect is explained by elementary hydrodynamic
      considerations.

PMID- 19392407
TI  - Simulation of elastic rupture in extension of entangled monodisperse polymer
      melts.
AB  - We use a Lagrangian finite element method to simulate experiments on continued
      and interrupted extensions of a highly entangled monodisperse polymer melt. It is
      demonstrated that delayed sample necking or rupture may be explained in terms of
      the original Doi-Edwards model augmented by the mechanism of chain stretching
      alone.

PMID- 19392408
TI  - Granular character of particle rafts.
AB  - We consider a monolayer of particles floating at a horizontal liquid-gas
      interface-a particle raft. Upon compressing the monolayer in a Langmuir trough,
      the particles at first pack but ultimately the monolayer buckles out of the
      plane. We measure the stress profile within the raft at the onset of buckling and
      show for the first time that such systems exhibit a Janssen effect: the stress
      decays exponentially away from the compressing barriers over a length scale that
      depends on the width of the trough. We find quantitative agreement between the
      rate of decay and the simple theory presented by Janssen and others. This
      demonstrates that particle rafts have a granular, as well as elastic, character,
      which is neglected by current models. Finally, we suggest that our experimental
      setup may be suitable for exploring granular effects in two dimensions without
      the complications of gravity and basal friction.

PMID- 19392409
TI  - Core-hole screening as a probe for a metal-to-nonmetal transition in lead
      clusters.
AB  - Metal clusters serve as model systems to study basic problems of electronic
      correlation. Vacuum ultraviolet light from the free-electron laser FLASH ionizes
      5d electrons from mass-separated negatively charged clusters, thus transiently
      leading to core-ionized neutral systems. Shielding of the core hole affects the
      electron binding energy. From the strong deviation from expectations of the
      metallic droplet and jellium models we conclude on reduced electronic shielding
      once the cluster size falls below about 20 atoms. This suggests a metal-to
      nonmetal transition, in agreement with previous local density approximation
      calculations.

PMID- 19392410
TI  - Emergence and size of the giant component in clustered random graphs with a given
      degree distribution.
AB  - Standard techniques for analyzing network models usually break down in the
      presence of clustering. Here we introduce a new analytic tool, the "free-excess
      degree" distribution, which extends the generating function framework, making it
      applicable for clustered networks (C>0). The methodology is general and provides
      a new expression for the threshold point at which the giant component emerges and
      shows that it scales as (1-C)(-1). In addition, the size of the giant component
      may be predicted even for more complicated scenarios such as the removal of a
      fixed fraction of nodes at random.

PMID- 19392411
TI  - Comment on "Violation of the zeroth law of thermodynamics in systems with
      negative specific heat".

PMID- 19392413
TI  - Comment on "Dynamic scaling of non-Euclidean interfaces".

PMID- 19392415
TI  - Evidence for universal four-body states tied to an Efimov trimer.
AB  - We report on the measurement of four-body recombination rate coefficients in an
      atomic gas. Our results obtained with an ultracold sample of cesium atoms at
      negative scattering lengths show a resonant enhancement of losses and provide
      strong evidence for the existence of a pair of four-body states, which is
      strictly connected to Efimov trimers via universal relations. Our findings
      confirm recent theoretical predictions and demonstrate the enrichment of the
      Efimov scenario when a fourth particle is added to the generic three-body
      problem.

PMID- 19392416
TI  - Magnetic and superfluid transitions in the one-dimensional spin-1 boson Hubbard
      model.
AB  - Recent progress in experiments on trapped ultracold atoms has made it possible to
      study the interplay between magnetism and superfluid-insulator transitions in the
      boson Hubbard model. We report on quantum Monte Carlo simulations of the spin-1
      boson Hubbard model in the ground state. For antiferromagnetic interactions
      favoring singlets, we present exact numerical evidence that the superfluid
      insulator transition is first (second) order for even (odd) Mott lobes. Inside
      even lobes, we search for nematic-to-singlet first order transitions. In the
      ferromagnetic case where transitions are all continuous, we map the phase diagram
      and show the superfluid to be ferromagnetic. We compare the quantum Monte Carlo
      phase diagram with a third order perturbation calculation.

PMID- 19392417
TI  - Negative-index media for matter-wave optics.
AB  - We consider the extension of optical metamaterials to matter waves and then the
      down scaling of metaoptics to nanometric wavelengths. We show that the generic
      property of pulsed comoving magnetic fields allows us to fashion the wave-number
      dependence of the atomic phase shift. It can be used to produce a transient
      negative group velocity of an atomic wave packet, which results into a negative
      refraction of the matter wave. Application to slow metastable argon atoms Ar(3P2)
      shows that the device is able to operate either as an efficient beam splitter or
      an atomic metalens.

PMID- 19392418
TI  - Macroscopic quantum electrodynamics and duality.
AB  - We discuss under what conditions the duality between electric and magnetic fields
      is a valid symmetry of macroscopic quantum electrodynamics. It is shown that
      Maxwell's equations in the absence of free charges satisfy duality invariance on
      an operator level, whereas this is not true for Lorentz forces and atom-field
      couplings in general. We prove that derived quantities such as Casimir forces,
      local-field corrected decay rates, as well as van der Waals potentials are
      invariant with respect to a global exchange of electric and magnetic quantities.
      This exact symmetry can be used to deduce the physics of new configurations on
      the basis of already established ones.

PMID- 19392419
TI  - Terahertz Bloch oscillator with a modulated bias.
AB  - Electrons performing Bloch oscillations in an energy band of a dc-biased
      superlattice in the presence of weak dissipation can potentially generate THz
      fields at room temperature. The realization of such a Bloch oscillator is a long
      standing problem due to the instability of a homogeneous electric field in
      conditions of negative differential conductivity. We establish the theoretical
      feasibility of stable THz gain in a long superlattice device in which the bias is
      quasistatically modulated by microwave fields. The modulation waveforms must have
      at least two harmonics in their spectra.

PMID- 19392420
TI  - Universally composable privacy amplification from causality constraints.
AB  - We consider schemes for secret key distribution which use as a resource
      correlations that violate Bell inequalities. We provide the first security proof
      for such schemes, according to the strongest notion of security, the so-called
      universally composable security. Our security proof does not rely on the validity
      of quantum mechanics, it solely relies on the impossibility of arbitrarily fast
      signaling between separate physical systems. This allows for secret communication
      in situations where the participants distrust their quantum devices.

PMID- 19392421
TI  - Hydrodynamical trigger mechanism for pulsar glitches.
AB  - We describe a new instability that may trigger the global unpinning of vortices
      in a spinning neutron star, leading to the transfer of angular momentum from the
      superfluid component to the star's crust. The instability, which is associated
      with the inertial r modes of a superfluid neutron star, sets in once the
      rotational lag in the system reaches a critical level. We demonstrate that our
      simple model agrees well with the observed glitch data. This new idea should
      stimulate work on more detailed neutron star models, which would account for the
      crustal shear stresses and magnetic field effects we have ignored.

PMID- 19392422
TI  - Dark matter from R2 gravity.
AB  - The modification of Einstein gravity at high energies is mandatory from a quantum
      approach. In this work, we point out that this modification necessarily
      introduces new degrees of freedom. We analyze the possibility that these new
      gravitational states can provide the main contribution to the nonbaryonic dark
      matter of the Universe. By following an effective field theory approach, we
      illustrate this idea with the first and simplest high energy modification of the
      Einstein-Hilbert action: R2 gravity.

PMID- 19392423
TI  - Fine-grained state counting for black holes in loop quantum gravity.
AB  - A state of a black hole in loop quantum gravity is given by a distribution of
      spins on punctures on the horizon. The distribution is of the Boltzmann type,
      with the area playing the role of the energy. In investigations where the total
      area was kept approximately constant, there was a kind of thermal equilibrium
      between the spins which have the same analogue temperature and the entropy was
      proportional to the area. If the area is precisely fixed, however, multiple
      constraints appear, different spins have different analogue temperatures and the
      entropy is not strictly linear in the area, but is bounded by a linear rise.

PMID- 19392424
TI  - Dilatation symmetry in higher dimensions and the vanishing of the cosmological
      constant.
AB  - A wide class of dilatation symmetric effective actions in higher dimensions leads
      to a vanishing four-dimensional cosmological constant. This requires no tuning of
      parameters and results from the absence of an allowed potential for the scalar
      dilaton field. The field equations admit many solutions with flat four
      dimensional space and nonvanishing gauge couplings. In a more general setting,
      these are candidates for asymptotic states of cosmological runaway solutions,
      where dilatation symmetry is realized dynamically if a fixed point is approached
      as time goes to infinity. Dilatation anomalies during the runaway can lift the
      degeneracy of solutions and lead to an observable dynamical dark energy.

PMID- 19392425
TI  - Search for proton decay via p-->e+pi0 and p-->micro+pi0 in a large water
      Cherenkov detector.
AB  - We have searched for proton decays via p-->e;{+}pi;{0} and p-->micro;{+}pi;{0}
      using data from a 91.7 kt.yr exposure of Super-Kamiokande-I and a 49.2 kt.yr
      exposure of Super-Kamiokande-II. No candidate events were observed with expected
      backgrounds induced by atmospheric neutrinos of 0.3 events for each decay mode.
      From these results, we set lower limits on the partial lifetime of 8.2 x 10;{33}
      and 6.6 x 10;{33} years at 90% confidence level for p-->e;{+}pi;{0} and p-
      >micro;{+}pi;{0} modes, respectively.

PMID- 19392427
TI  - J/psi production at HERA.
AB  - We consider the J/psi photoproduction data collected at the DESY ep collider HERA
      in the light of next-to-leading order predictions for the color-singlet yield and
      polarization. We find that, while the shapes of inclusive distributions in the
      transverse momentum and inelasticity are well reproduced, the experimental rates
      are larger than those given by the color-singlet contribution alone. Furthermore,
      the next-to-leading order calculation predicts the J/psi's to be mostly
      longitudinally polarized at high transverse momentum in contrast with the trend
      of the preliminary data from the ZEUS Collaboration.

PMID- 19392429
TI  - Test of the conserved vector current hypothesis in T=1/2 mirror transitions and
      new determination of |V ud|.
AB  - The V{ud} element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix has
      traditionally been determined from the analysis of data in nuclear superallowed
      0;{+}-->0;{+} transitions, neutron decay, and pion beta decay. After providing a
      new test of the conserved vector current hypothesis, we present here a new
      independent determination of |V{ud}| from a set of five T=1/2 nuclear mirror
      transitions. The extracted value, |V{ud}|=0.9719+/-0.0017, is at 1.2 combined
      standard deviations from the value obtained from superallowed 0;{+}-->0;{+}
      transitions and has a precision comparable to the value obtained from neutron
      decay experiments.

PMID- 19392428
TI  - System size, energy, and centrality dependence of pseudorapidity distributions of
      charged particles in relativistic heavy-ion collisions.
AB  - We present the first measurements of the pseudorapidity distribution of primary
      charged particles in Cu+Cu collisions as a function of collision centrality and
      energy, sqrt[s_{NN}]=22.4, 62.4, and 200 GeV, over a wide range of
      pseudorapidity, using the PHOBOS detector. A comparison of Cu+Cu and Au+Au
      results shows that the total number of produced charged particles and the rough
      shape (height and width) of the pseudorapidity distributions are determined by
      the number of nucleon participants. More detailed studies reveal that a more
      precise matching of the shape of the Cu+Cu and Au+Au pseudorapidity distributions
      over the full range of pseudorapidity occurs for the same N{part}/2A rather than
      the same N_{part}. In other words, it is the collision geometry rather than just
      the number of nucleon participants that drives the detailed shape of the
      pseudorapidity distribution and its centrality dependence at RHIC energies.

PMID- 19392430
TI  - Evidence for a change in the nuclear mass surface with the discovery of the most
      neutron-rich nuclei with 17<or=Z<or=25.
AB  - The results of measurements of the production of neutron-rich nuclei by the
      fragmentation of a 76Ge beam are presented. The cross sections were measured for
      a large range of nuclei including 15 new isotopes that are the most neutron-rich
      nuclides of the elements chlorine to manganese (50Cl, 53Ar, ;{55,56}K,
      ;{57,58}Ca, ;{59,60,61}Sc, ;{62,63}Ti, ;{65,66}V, 68Cr, 70Mn). The enhanced cross
      sections of several new nuclei relative to a simple thermal evaporation
      framework, previously shown to describe similar production cross sections,
      indicates that nuclei in the region around 62Ti might be more stable than
      predicted by current mass models and could be an indication of a new island of
      inversion similar to that centered on 31Na.

PMID- 19392431
TI  - Large beta-delayed neutron emission probabilities in the 78Ni region.
AB  - The beta-delayed neutron branching ratios (P{betan}) for nuclei near doubly magic
      78Ni have been directly measured using a new method combining high-resolution
      mass separation, reacceleration, and digital beta-gamma spectroscopy of 238U
      fission products. The P{betan} values for the very neutron-rich isotopes ;{76
      78}Cu and 83Ga were found to be much higher than previously reported and
      predicted. Revised calculations of the betan process, accounting for new mass
      measurements and an inversion of the pi2p{3/2} and pi1f{5/2} orbitals, are in
      better agreement with these new experimental results.

PMID- 19392432
TI  - Isoscaling as a measure of symmetry energy in the lattice gas model.
AB  - The energetic properties of nuclear clusters inside a low-density, finite
      temperature medium are studied with a lattice gas model including isospin
      dependence and Coulomb forces. Important deviations are observed with respect to
      the Fisher approximation of an ideal gas of noninteracting clusters, but a simple
      modified energy-density functional can still describe the global energetics. The
      multifragmentation regime is dominated by combinatorial effects, but the
      isoscaling of the largest fragment appears to be a promising observable for the
      experimental measurement of the symmetry energy.

PMID- 19392433
TI  - Separation of two-electron photoexcited atomic processes near the inner-shell
      threshold.
AB  - By means of a high resolution resonant inelastic x-ray scattering spectroscopy,
      we have for the first time separated spectral features pertaining to different
      two-electron atomic processes in the vicinity of an inner-shell threshold.
      Contributions of shakeoff, shakeup, and resonant 1s3p double excitations were
      extracted from the Ar KM-M{2,3}M x-ray satellite line intensity measured as a
      function of photon energy from [1s3p] double excitation threshold to saturation.
      The isolated [1s3p]nln'l' excitation spectrum is critically compared to the
      outcome of the multiconfiguration Dirac-Fock model with relaxation.

PMID- 19392434
TI  - Geometrical phase driven predissociation: lifetimes of 2 2 A' levels of H3.
AB  - We discuss the role of the geometric phase in predissociation dynamics of
      vibrational states near a conical intersection of two electronic potential
      surfaces of a D{3h} molecule. We present a method to calculate lifetimes and
      positions of predissociated vibrational states (Feshbach resonances) for such X3
      molecules. The method accounts for the two coupled three-body potential surfaces.
      As an example, the method is applied to obtain vibrational levels of the 2;{2}A'
      electronic state of H3. The three-body recombination rate coefficient for the
      H+H+H-->H{2}+H process is estimated.

PMID- 19392435
TI  - Novel phenomena in very-low-frequency strong fields.
AB  - Atomic ionization by lasers of very low frequency, once thought to be a classical
      limit or a "tunneling limit", presents unique spectral features unlike any
      tunneling phenomenon. The identity of the atom is the controlling factor, leading
      to photoelectron spectra with well-defined peaks and valleys that persist over
      wide ranges of field parameters. Such a spectrum was observed 20 years ago in
      ionization of xenon at 10.6 microm.

PMID- 19392436
TI  - Origin, evolution, and imaging of vortices in atomic processes.
AB  - Vortices are usually associated with systems containing large numbers of
      particles. Of particular topical interest though are those formed within atomic
      scale wave functions and observed in macroscopic systems such as superfluids and
      quantum condensates. We uncover them here in one of the most fundamental quantum
      systems consisting of just one electron and two protons. Moreover, the results of
      novel simulations of the dynamics of this system reveal previously unknown
      mechanisms of angular momentum transfer and new ways to image atomic-scale
      quantized vortices at macroscopic distances. Probing of vortices and vortex
      driven dynamics in quantum systems is thereby illustrated.

PMID- 19392437
TI  - Collective lamb shift in single photon Dicke superradiance.
AB  - The collective Lamb shift and associated radiative decay of a large cloud of
      radius R containing N atoms uniformly excited by one photon of wavelength lambda
      is analyzed. It is shown that the time evolution of the symmetric state prepared
      by single photon absorption in the limit R>>lambda is similar to that encountered
      in the Dicke limit of small sample (R<<lambda) superradiance. The theory includes
      virtual (counterrotating) terms naturally and thus provides a simple calculation
      of the collective Lamb shift of a single Dicke state.

PMID- 19392438
TI  - Generation of an axially asymmetric Bessel-like beam from a metallic
      subwavelength aperture.
AB  - An electromagnetic nondiffractive Bessel-like beam from a subwavelength aperture
      is generated by placing a metallic circular gratinglike structure in front of the
      aperture. When the incident wave is linearly polarized, the beam is axially
      asymmetric. The beam possesses fluctuating, but approximately uniform, intensity
      distribution along its longitudinal axis. The full width at half maximum of the
      beam remains less than two wavelengths over nearly ten wavelengths. Our
      experimental results are in good agreement with the simulation results and
      analytical results.

PMID- 19392439
TI  - Topology of light's darkness.
AB  - We numerically study the topology of optical vortex lines (nodal lines) in
      volumes of optical speckle, modeled as superpositions of random plane waves. It
      is known that the vortex lines may be infinitely long, or form closed loops.
      Loops are occasionally threaded by infinite lines, or linked with other loops. We
      find the probability of a loop not being threaded decays exponentially with the
      length of the loop. This behavior has a similarity to scaling laws studied in
      superfluid turbulence, and polymers modeled as random walks.

PMID- 19392426
TI  - Improved measurement of B+ --> rho+ rho0 and determination of the quark-mixing
      phase angle alpha.
AB  - We present improved measurements of the branching fraction B, the longitudinal
      polarization fraction f{L}, and the direct CP asymmetry A{CP} in the B meson
      decay channel B;{+}-->rho;{+}rho;{0}. The data sample was collected with the
      BABAR detector at SLAC. The results are B(B;{+}-->rho;{+}rho;{0})=(23.7+/-1.4+/
      1.4) x 10;{-6}, f{L}=0.950+/-0.015+/-0.006, and A{CP}=-0.054+/-0.055+/-0.010,
      where the uncertainties are statistical and systematic, respectively. Based on
      these results, we perform an isospin analysis and determine the Cabibbo-Kobayashi
      Maskawa phase angle alpha=arg(-V{td}V{tb};/V{ud}V{ub}) to be (92.4{-6.5};{+6.0})
      degrees.

PMID- 19392440
TI  - Dissipation-induced coherent structures in Bose-Einstein condensates.
AB  - We discuss how to engineer the phase and amplitude of a complex order parameter
      using localized dissipative perturbations. Our results are applied to generate
      and control various types of atomic nonlinear matter waves (solitons) by means of
      localized dissipative defects.

PMID- 19392441
TI  - Angle-dependent ultrasonic transmission through plates with subwavelength hole
      arrays.
AB  - We study the angle and frequency dependence of sound transmission through water
      immersed perforated aluminum plates. Three types of resonances are found to
      govern the acoustic properties of the plates: lattice resonances in periodic
      arrays, Fabry-Perot modes of the hole cavities, and elastic Lamb modes. The last
      two of them are still present in random arrays and have no parallel in optical
      transmission through holes. These modes are identified by comparing experiment
      with various levels of theoretical analysis, including full solution of the
      elasto-acoustic wave equations. We observe strong mixture of different
      transmission mechanisms, giving rise to unique acoustic behavior and opening new
      perspectives for exotic wave phenomena.

PMID- 19392442
TI  - Force balance at the transition from selective withdrawal to viscous entrainment.
AB  - We simulate the evolution of the steady-state interface in the selective
      withdrawal regime. Selective withdrawal ends when the upward pull exerted by the
      viscous flow in the withdrawing liquid layer overcomes the downward force due to
      surface tension. The lower-layer dynamics are unimportant. The dominant
      contribution to the surface-tension force comes from the large area where the
      interface is weakly deflected, instead of the small area where the surface is
      most distorted. A scaling estimate based on this idea yields results that agree
      quantitatively with both simulations and previous experiments.

PMID- 19392443
TI  - Mesoscopic void structures in cobalt nanocrystal films formed from drying
      concentrated colloidal solutions.
AB  - Here we report the formation of void (hole) structures when concentrated
      colloidal solutions of magnetic nanocrystals are subjected to a magnetic field
      during slow evaporation. This presents a new type of solid mesostructure obtained
      by self-assembly of nanocrystals. The voids are characterized by a cylindrical
      shape with either circular or elliptical base. We show that the morphology of
      these patterns is essentially controlled by the fraction of the volume occupied
      by the magnetic phase to the total volume of the film. Monte Carlo simulations
      carried out using a Stockmayer fluid model agree remarkably well with the
      experiments for the formation of void structures in the range of considered
      volume fractions.

PMID- 19392444
TI  - Simple mechanism for reversals of earth's magnetic field.
AB  - We show that a model, recently used to describe all the dynamical regimes of the
      magnetic field generated by the dynamo effect in the von Karman sodium
      experiment, also provides a simple explanation of the reversals of Earth's
      magnetic field, despite strong differences between both systems. The validity of
      the model relies on the smallness of the magnetic Prandtl number.

PMID- 19392445
TI  - Rarefaction acceleration and kinetic effects in thin-foil expansion into a
      vacuum.
AB  - The collisionless expansion into a vacuum of a thin plasma foil adiabatically
      cooling down is studied with a particular emphasis on the evolution of the
      electron distribution function. It is shown that during the expansion the bulk of
      the distribution function evolves towards a top-hat distribution. As a result,
      while the electrons globally lose energy in favor of the ions, the rarefaction
      wave accelerates until it reaches the center of the foil. The electron
      temperature becomes strongly inhomogeneous, with a maximum in the center of the
      foil, a strong dip in the outer part of the foil, and a constancy of the initial
      temperature in the far corona.

PMID- 19392446
TI  - Stable GeV ion-beam acceleration from thin foils by circularly polarized laser
      pulses.
AB  - A stable relativistic ion acceleration regime for thin foils irradiated by
      circularly polarized laser pulses is suggested. In this regime, the "light-sail"
      stage of radiation pressure acceleration for ions is smoothly connected with the
      initial relativistic "hole-boring" stage, and a defined relationship between
      laser intensity I0, foil density n{0}, and thickness l{0} should be satisfied.
      For foils with a wide range of n{0}, the required I0 and l{0} for the regime are
      theoretically estimated and verified with the particle-in-cell code ILLUMINATION.
      It is shown for the first time by 2D simulations that high-density monoenergetic
      ion beams with energy above GeV/u and divergence of 10 degrees are produced by
      circularly polarized lasers at intensities of 10;{22} W/cm;{2}, which are within
      reach of current laser systems.

PMID- 19392447
TI  - Use of a linear Paul trap to study random noise-induced beam degradation in high
      intensity accelerators.
AB  - A random noise-induced beam degradation that can affect intense beam transport
      over long propagation distances has been experimentally studied by making use of
      the transverse beam dynamics equivalence between an alternating-gradient (AG)
      focusing system and a linear Paul trap system. For the present studies, machine
      imperfections in the quadrupole focusing lattice are considered, which are
      emulated by adding small random noise on the voltage waveform of the quadrupole
      electrodes in the Paul trap. It is observed that externally driven noise
      continuously produces a nonthermal tail of trapped ions, and increases the
      transverse emittance almost linearly with the duration of the noise.

PMID- 19392448
TI  - Nonlinear development of streaming instabilities in strongly magnetized plasma.
AB  - The nonlinear development of streaming instabilities in the current layers formed
      during magnetic reconnection with a guide field is explored. Theory and 3D
      particle-in-cell simulations reveal two distinct phases. First, the parallel
      Buneman instability grows and traps low velocity electrons. The remaining
      electrons then drive two forms of turbulence: the parallel electron-electron two
      stream instability and the nearly perpendicular lower-hybrid instability. The
      high velocity electrons resonate with the turbulence and transfer momentum to the
      ions and low velocity electrons.

PMID- 19392449
TI  - Analytically solvable model of nonlinear oscillations in a cold but viscous and
      resistive plasma.
AB  - A method for solving model nonlinear equations describing plasma oscillations in
      the presence of viscosity and resistivity is given. By first going to the
      Lagrangian variables and then transforming the space variable conveniently, the
      solution in parametric form is obtained. It involves simple elementary functions.
      Our solution includes all known exact solutions for an ideal cold plasma and a
      large class of new ones for a more realistic plasma. A new nonlinear effect is
      found of splitting of the largest density maximum, with a saddle point between
      the peaks so obtained. The method may sometimes be useful where inverse
      scattering fails.

PMID- 19392450
TI  - Quantitative radiography of magnetic fields using neutron spin phase imaging.
AB  - We report on a novel neutron radiography technique that uses the Ramsey
      principle, a method similar to neutron spin echo. For the first time quantitative
      imaging measurements of magnetic objects and fields could be performed. The
      strength of the spin-dependent magnetic interaction is detected by a change in
      the Larmor precession frequency of the neutron spins. Hence, one obtains in
      addition to the normal attenuation radiography image a so-called neutron spin
      phase image, which provides a two-dimensional projection of the magnetic field
      integrated over the neutron flight path.

PMID- 19392451
TI  - Influence of pressure on quasielastic scattering in glasses: relationship to the
      boson peak.
AB  - We report unexpectedly strong variations in the quasielastic scattering (QES)
      intensity in glasses under pressure. Analysis of the data reveals strong
      correlations between pressure-induced changes in the QES intensity and the
      intensity of the boson peak. This observation emphasizes a direct relationship
      between these two components of the fast dynamics. In addition, we observe
      changes of the QES spectral shape that can be interpreted as pressure-induced
      variations in the underlying energy landscape.

PMID- 19392452
TI  - Two-dimensional heterogeneous dynamics at the surface of a colloidal suspension.
AB  - We report on an x-ray photon correlation spectroscopy experiment investigating
      the surface structure and dynamics of colloidal particles suspended in a
      supercooled viscous liquid. The static structure factor in the direction parallel
      and perpendicular to the surface reveals a more disordered structure at the
      surface as compared to the bulk. The particles display heterogeneous ballistic
      dynamics parallel to the surface. The particle dynamics in the direction
      perpendicular to the surface is much slower and does not show the hallmarks of
      ballistic motion.

PMID- 19392453
TI  - Semiflexible fully packed loop model and interacting rhombus tilings.
AB  - Motivated by a recent adsorption experiment [M. O. Blunt, Science 322, 1077
      (2008)10.1126/science.1163338], we study tilings of the plane with three
      different types of rhombi. An interaction disfavors pairs of adjacent rhombi of
      the same type. This is shown to be a special case of a model of fully packed
      loops with interactions between monomers at distance two along a loop. We solve
      this model using Coulomb gas techniques and show that its critical exponents vary
      continuously with the interaction strength. At low temperature it undergoes a
      Kosterlitz-Thouless transition to an ordered phase, which is predicted from
      numerics to occur at a temperature T approximately 110 K in the experiments.

PMID- 19392454
TI  - Superionic conductivity in the Li4C60 fulleride polymer.
AB  - We report on the extraordinary superionic conductivity in the fulleride polymer
      Li4C60, a crystalline material with no disorder. 7Li, NMR, and dc frequency
      dependent conductivity show uncorrelated ionic hopping across small energy
      barriers (DeltaE_{a} approximately 200 meV) and an ionic conductivity of 10;{-2}
      S/cm at room temperature, higher than in "standard" ionic conductors. Ab initio
      calculations of the molecular structure find intrinsic unoccupied interstitial
      sites that can be filled by Li+ cations in stoichiometric Li4C60 even at low
      temperatures. The low energy required for the occupation of these sites allows a
      sizable Li+ diffusion above 130 K. The results suggest novel application of
      lithium intercalated fullerides as electrodes in Li ions batteries.

PMID- 19392455
TI  - Mixed barrier model for the mixed glass former effect in ion conducting glasses.
AB  - Mixing two types of glass formers in ion conducting glasses can be exploited to
      lower conductivity activation energy and thereby increasing the ionic
      conductivity, a phenomenon known as the mixed glass former effect (MGFE). We
      develop a model for this MGFE, where activation barriers for individual ion jumps
      get lowered in inhomogeneous environments containing both types of network
      forming units. Fits of the model to experimental data allow one to estimate the
      strength of the barrier reduction, and they indicate a spatial clustering of the
      two types of network formers. The model predicts a time-temperature superposition
      of conductivity spectra onto a common master curve independent of the mixing
      ratio.

PMID- 19392456
TI  - Theory of nanocluster size distributions from ion beam synthesis.
AB  - Ion beam synthesis of nanoclusters is studied via both kinetic Monte Carlo
      simulations and the self-consistent mean-field solution to a set of coupled rate
      equations. Both approaches predict the existence of a steady-state shape for the
      cluster-size distribution that depends only on a characteristic length determined
      by the effective diffusion coefficient, the ion solubility, and the volumetric
      ion flux. The average cluster size in the steady-state regime is determined by
      the implanted species or matrix interface energy.

PMID- 19392457
TI  - Shape transitions of epitaxial islands during strained layer growth: anatase
      TiO2(001) on SrTiO3(001).
AB  - Extended annealing in UHV causes the surface region of SrTiO3(001) to become
      enriched with TiO2, resulting in the formation of epitaxial islands of anatase
      TiO2(001). The islands are studied using UHV scanning electron microscopy (SEM),
      which reveals the changes in morphology during growth induced by misfit strain.
      Starting from a square island, two types of shape transition are observed. In the
      first, between 1000 and 1030 degrees C, the anatase islands elongate in length
      and narrow in width. This growth behavior follows the Tersoff-Tromp model [Phys.
      Rev. Lett. 70, 2782 (1993)10.1103/PhysRevLett.70.2782]. In the second growth
      mode, between 930 and 1000 degrees C, the islands relieve strain by the formation
      of trenches in the middle of each side of the square, thereby evolving into
      crosses. This shape arises because the lower annealing temperature imposes a
      kinetic constraint on the detachment of atoms necessary for island narrowing.

PMID- 19392458
TI  - Rapid coarsening of ion beam ripple patterns by defect annihilation.
AB  - Ripple patterns formed on Pt(111) through grazing incidence ion beam erosion
      coarsen rapidly. At and below 450 K coarsening of the patterns is athermal and
      kinetic, unrelated to diffusion and surface free energy. Similar to the situation
      for sand dunes, coarsening takes place through annihilation reactions of mobile
      defects in the pattern. The defect velocity derived on the basis of a simple
      model agrees quantitatively with the velocity of monatomic steps illuminated by
      the ion beam.

PMID- 19392459
TI  - Dense low-coordination phases of lithium.
AB  - Ab initio density-functional-theory calculations and a structure-searching
      technique are used to identify candidate high-pressure phases of lithium (Li). We
      predict threefold coordinated structures to be stable in the pressure range 40
      450 GPa and fourfold structures at higher pressures. We describe these low
      coordination phases as elemental electrides. All of the stable phases are
      metallic but the Cmca-24 structure, and two distortions of it which are
      marginally the most stable in the pressure range 86-106 GPa, are nearly
      semiconducting with densities of electronic states at the Fermi energy of only a
      few percent of the free-electron value.

PMID- 19392460
TI  - Pressure-driven metal-insulator transition in hematite from dynamical mean-field
      theory.
AB  - The local density approximation combined with dynamical mean-field theory is
      applied to study the paramagnetic and magnetically ordered phases of hematite
      Fe2O3 as a function of volume. As the volume is decreased, a simultaneous first
      order insulator-metal and high-spin to low-spin transition occurs close to the
      experimental value of the critical volume. The high-spin insulating phase is
      destroyed by a progressive reduction of the spectral gap with increasing
      pressure, upon closing of which the high-spin phase becomes unstable. We conclude
      that the transition in Fe2O3 at approximately 50 GPa can be described as an
      electronically driven volume collapse.

PMID- 19392461
TI  - Competition between Anderson localization and antiferromagnetism in correlated
      lattice fermion systems with disorder.
AB  - The magnetic ground state phase diagram of the disordered Hubbard model at half
      filling is computed in dynamical mean-field theory supplemented with the spin
      resolved, typical local density of states. The competition between many-body
      correlations and disorder is found to stabilize paramagnetic and
      antiferromagnetic metallic phases at weak interactions. Strong disorder leads to
      Anderson localization of the electrons and suppresses the antiferromagnetic long
      range order. Slater and Heisenberg antiferromagnets respond characteristically
      differently to disorder. The results can be tested with cold fermionic atoms
      loaded into optical lattices.

PMID- 19392462
TI  - Fractional statistics and quantum scaling properties of the Hubbard chain with
      bond-charge interaction.
AB  - We present a detailed study of the ground state and low-temperature properties of
      the integrable Hubbard model with bond-charge interaction, including its
      conducting properties and scaling behavior near the U-driven quantum phase
      transitions. Remarkably, the model displays fractional statistical properties,
      which enlighten the nature of various physical properties, such as the fractional
      elementary excitations, and give rise to a disordered condensate and phase
      separation in k space, as well as to a topological change in the generalized
      Fermi surface at half filling.

PMID- 19392463
TI  - Hole-nuclear spin interaction in quantum dots.
AB  - We have measured the carrier spin dynamics in p-doped InAs/GaAs quantum dots by
      pump-probe and time-resolved photoluminescence experiments. We obtained
      experimental evidence of the hyperfine interaction between hole and nuclear
      spins. In the absence of an external magnetic field, our calculations based on
      dipole-dipole coupling between the hole and the quantum dot nuclei lead to a hole
      spin dephasing time for an ensemble of dots of 14 ns, in close agreement with
      experiments.

PMID- 19392464
TI  - Electronic refrigeration of a two-dimensional electron gas.
AB  - Measurements are presented of a device designed to cool a 6 microm;{2} region of
      2D electron gas using quantum dots. Electrostatic effects are found to be
      significant in the device, and a model that accounts for them is developed. At
      ambient electron temperatures above 120 mK the results are consistent with the
      model and the base temperature of the cooled region is estimated. At an ambient
      electron temperature of 280 mK, the 6 microm;{2} region is found to be cooled
      below 190 mK. Below 120 mK the results deviate from predictions, which is
      attributed to reduced electron-electron scattering rates.

PMID- 19392465
TI  - Vibrational nonequilibrium effects in the conductance of single molecules with
      multiple electronic states.
AB  - Vibrational nonequilibrium effects in charge transport through single-molecule
      junctions are investigated. Focusing on molecular bridges with multiple
      electronic states, it is shown that electronic-vibrational coupling triggers a
      variety of vibronic emission and absorption processes, which influence the
      conductance properties and mechanical stability of single-molecule junctions
      profoundly. Employing a master equation and a nonequilibrium Green's function
      approach, these processes are analyzed in detail for a generic model of a
      molecular junction and for benzenedibutanethiolate bound to gold electrodes.

PMID- 19392466
TI  - Quantitative estimation of exchange interaction energy using two-electron
      vertical double quantum dots.
AB  - We use Pauli-spin blockade in two-electron vertical double quantum dots to
      quantitatively estimate the exchange energy J in a wide range of interdot level
      detuning Delta and fully compare it with calculations. Pauli-spin blockade is
      lifted via a singlet- (S-)triplet (T) transition mediated by hyperfine coupling,
      which abruptly occurs in our devices when the S-T transition energy or J is
      compensated by the Zeeman energy. We use this feature to derive J depending on
      Delta between the S-S and T-T resonances. The obtained J versus Delta including
      the resonance effect is perfectly reproduced by Hubbard model calculations.

PMID- 19392467
TI  - Exact scattering eigenstates, many-body bound states, and nonequilibrium current
      in an open quantum dot system.
AB  - We obtain an exact many-body scattering eigenstate in an open quantum dot system.
      The scattering state is not in the form of the Bethe eigenstate in the sense that
      the wave number set of the incoming plane wave is not conserved during the
      scattering and many-body bound states appear. By using the scattering state, we
      study the average nonequilibrium current through the quantum dot under a finite
      bias voltage. The current-voltage characteristics that we obtained by taking the
      two-body bound state into account is qualitatively similar to several known
      results.

PMID- 19392468
TI  - Quantum Goos-Hanchen effect in graphene.
AB  - The Goos-Hanchen (GH) effect is an interference effect on total internal
      reflection at an interface, resulting in a shift sigma of the reflected beam
      along the interface. We show that the GH effect at a p-n interface in graphene
      depends on the pseudospin (sublattice) degree of freedom of the massless Dirac
      fermions, and find a sign change of sigma at angle of incidence alpha=arcsin
      sqrt[sinalpha{c}] determined by the critical angle alpha{c} for total reflection.
      In an n-doped channel with p-doped boundaries the GH effect doubles the
      degeneracy of the lowest propagating mode, introducing a twofold degeneracy on
      top of the usual spin and valley degeneracies. This can be observed as a stepwise
      increase by 8e;{2}/h of the conductance with increasing channel width.

PMID- 19392469
TI  - Magnetoelectric polarizability and axion electrodynamics in crystalline
      insulators.
AB  - The orbital motion of electrons in a three-dimensional solid can generate a
      pseudoscalar magnetoelectric coupling theta, a fact we derive for the single
      particle case using a recent theory of polarization in weakly inhomogeneous
      materials. This polarizability theta is the same parameter that appears in the
      "axion electrodynamics" Lagrangian DeltaL_{EM}=(thetae;{2}/2pih)E.B, which is
      known to describe the unusual magnetoelectric properties of the three-dimensional
      topological insulator (theta=pi). We compute theta for a simple model that
      accesses the topological insulator and discuss its connection to the surface Hall
      conductivity. The orbital magnetoelectric polarizability can be generalized to
      the many-particle wave function and defines the 3D topological insulator, like
      the integer quantum Hall effect, in terms of a topological ground-state response
      function.

PMID- 19392470
TI  - Hamiltonian decomposition for bulk and surface states.
AB  - We demonstrate that a tight-binding Hamiltonian with nearest- and next-nearest
      neighbor hopping integrals can be decomposed into bulk and boundary parts for
      honeycomb lattice systems. The Hamiltonian decomposition reveals that next
      nearest-neighbor hopping causes sizable changes in the energy spectrum of surface
      states even if the correction to the energy spectrum of bulk states is
      negligible. By applying the Hamiltonian decomposition to edge states in graphene
      systems, we show that the next-nearest-neighbor hopping stabilizes the edge
      states. The application of Hamiltonian decomposition to a general lattice system
      is discussed.

PMID- 19392471
TI  - Shaping the fluorescent emission by lattice resonances in plasmonic crystals of
      nanoantennas.
AB  - We demonstrate that the emission of light by fluorescent molecules in the
      proximity of periodic arrays of nanoantennas or plasmonic crystals can be
      strongly modified when the arrays are covered by a dielectric film. The coupling
      between localized surface plasmon resonances and photonic states leads to surface
      modes which increase the density of optical states and improve light extraction.
      Excited dye molecules preferentially decay radiatively into these modes,
      exhibiting an enhanced and directional emission.

PMID- 19392472
TI  - Evidence for a nodal-line superconducting state in LaFePO.
AB  - In several iron-arsenide superconductors there is strong evidence for a fully
      gapped superconducting state consistent with either a conventional s-wave
      symmetry or an unusual s{+/-} state where the gap changes sign between the
      electron and hole Fermi-surface sheets. Here we report measurements of the
      penetration depth lambda(T) in very clean samples of the related iron-phosphide
      superconductor, LaFePO, at temperatures down to approximately 100 mK. We find
      that lambda(T) varies approximately linearly with T strongly suggesting the
      presence of gap nodes in this compound. Taken together with other data, this
      suggests the gap function is not universal for all pnictide superconductors.

PMID- 19392473
TI  - Observation of the Josephson effect in Pb/Ba1-xKxFe2As2 single crystal junctions.
AB  - We have fabricated c-axis Josephson junctions on single crystals of Ba1-xKxFe2As2
      by using Pb as the counterelectrode in two geometries, planar and point contact.
      Junctions in both geometries show resistively shunted junction I-V curves below
      the T{C} of the counterelectrode. Microwave induced steps were observed in the I
      V curves, and the critical currents are suppressed with an in-plane magnetic
      field with well-defined modulation periods indicating that the Josephson current
      is flowing in a manner consistent with the small to intermediate sized junction
      limit. I{C}R{N} products of up to 0.3 mV have been observed in these junctions at
      4.2 K. The observation of Josephson coupling along the c axis between Ba1
      xKxFe2As2 and a conventional superconductor suggests the existence of an s-wave
      symmetry in this class of iron pnictide superconductors.

PMID- 19392474
TI  - Role of fluorine in the iron pnictides: phonon softening and effective hole
      doping.
AB  - Using a first-principles approach, we investigate the influence of fluorine
      doping on the electronic structure, lattice dynamics, and electron-phonon
      coupling in LaFeAsO. In order to explore properties which are not described by
      the virtual crystal approximation, we explicitly simulate the F doping using a
      supercell model. Our analysis reveals that the relaxation of the crystal lattice
      around the dopant modifies the lattice dynamics in agreement with recent
      experimental data. In addition, we find that the doped electronic charge does not
      localize on the two-dimensional Fe plane. The net charge variation in this plane
      upon doping corresponds instead to a slight hole doping.

PMID- 19392475
TI  - Low-temperature magnetothermal transport investigation of a Ni-based
      superconductor BaNi2As2: evidence for fully gapped superconductivity.
AB  - We have performed low-temperature specific heat and thermal conductivity
      measurements of the Ni-based superconductor BaNi2As2 (T{c}=0.7 K) in a magnetic
      field. In a zero field, thermal conductivity shows T-linear behavior in the
      normal state and exhibits a BCS-like exponential decrease below T{c}. The field
      dependence of the residual thermal conductivity extrapolated to zero temperature
      is indicative of a fully gapped superconductor. This conclusion is supported by
      the analysis of the specific heat data, which are well fit by the BCS temperature
      dependence from T{c} down to the lowest temperature of 0.1 K.

PMID- 19392476
TI  - Magnetoelectric memory effect of the nonpolar phase with collinear spin structure
      in multiferroic MnWO4.
AB  - The novel memory effect of a nonpolar paraelectric phase with a collinear spin
      structure has been observed in a magnetoelectric multiferroic material MnWO4.
      Since the ferroelectric polarization arises from a noncollinear spin structure,
      in a new class of magnetoelectric multiferroic materials with a spiral-spin
      structure, the information of ferroelectric domains should be lost in the
      collinear spin phase. However, in MnWO4, it has been found that the domain states
      in the ferroelectric phase are memorized even in the nonpolar phase with a
      collinear spin structure, when the phase transition is of the first-order type.
      Here we demonstrate a magnetoelectric memory effect that the ferroelectric single
      domain state can be reproduced from the paraelectric phase by a magnetic field.
      We propose the nuclei growth model, in which the small ferroelectric embryos keep
      the polarization state in the nonpolar collinear spin phase.

PMID- 19392477
TI  - Current-induced control of spin-wave attenuation.
AB  - The current-induced modification of the attenuation of a propagating spin wave in
      a magnetic nanowire is studied theoretically and numerically. The attenuation
      length of spin wave can increase when the spin waves and electrons move in the
      same direction. It is directly affected by the nonadiabaticity of the spin
      transfer torque and thus can be used to estimate the nonadiabaticity. When the
      nonadiabatic spin torque is sufficiently large, the attenuation length becomes
      negative, resulting in the amplification of spin waves.

PMID- 19392478
TI  - Zero temperature phase diagram of the Kitaev model.
AB  - We show that the zero-temperature phase diagram of the vortex free sector of the
      Kitaev model is in one-to-one correspondence with that of the classical dimer
      model on the same lattice. We find that the model generically has three distinct
      phases. On a honeycomb lattice with a 3 x 3 fundamental domain all three phases
      are accessible. As the couplings are varied, there are two distinct transitions.
      The new transition is one to a gapped phase that opens up in the interior of the
      B phase.

PMID- 19392479
TI  - Direct observation of stochastic domain-wall depinning in magnetic nanowires.
AB  - The stochastic field-driven depinning of a domain wall pinned at a notch in a
      magnetic nanowire is directly observed using magnetic x-ray microscopy with high
      lateral resolution down to 15 nm. The depinning-field distribution in Ni80Fe20
      nanowires considerably depends on the wire width and the notch depth. The
      difference in the multiplicity of domain-wall types generated in the vicinity of
      a notch is responsible for the observed dependence of the stochastic nature of
      the domain-wall depinning field on the wire width and the notch depth. Thus the
      random nature of the domain-wall depinning process is controllable by an
      appropriate design of the nanowire.

PMID- 19392480
TI  - Continuous voltage tunability of intersubband relaxation times in coupled SiGe
      quantum well structures using ultrafast spectroscopy.
AB  - We demonstrate continuous voltage control of the nonradiative transition lifetime
      in semiconductor heterostructures. The results were obtained by picosecond time
      resolved experiments on biased SiGe valence band quantum well structures using a
      free electron laser. By varying the applied voltage, the intersubband hole
      relaxation times for quantum well structures were varied by a factor of 2 as the
      wave functions and their overlaps were tuned. The range of magnitudes for the
      lifetime indicates a possible route to silicon-based quantum cascade lasers.

PMID- 19392481
TI  - Universal properties of ferroelectric domains.
AB  - Based on the Ginzburg-Landau approach, we generalize the Kittel theory and derive
      the interpolation formula for the temperature evolution of a multidomain
      polarization profile P(x,z). We resolve the long-standing problem of the near
      surface polarization behavior in ferroelectric domains and demonstrate
      polarization vanishing instead of the usually assumed fractal domain branching.
      We propose an effective scaling approach to compare the properties of different
      domain-containing ferroelectric plates and films.

PMID- 19392482
TI  - Coexistence of melting and growth during heating of a semicrystalline polymer.
AB  - The coexistence of melting and growth during heating is observed by molecular
      dynamics simulations of semicrystalline entangled polymers. During heating, some
      microcrystalline domains (MCDs) are melted while others are still growing, which
      can be associated with multiple-peaked melting endotherms. The growth of MCD's
      stability is related to the increase of molecular disorder. The increasing of the
      stem length during annealing close to the melting point is contributed by the
      orientational correlation in the semimelted surface regions while direct trans
      trans states are decreasing which increases the flexibility and mobility of the
      crystalline stems.

PMID- 19392483
TI  - Unusual dielectric and electrical switching behavior in the de Vries smectic A
      phase of two organosiloxane derivatives.
AB  - X-ray, electrical, electro-optical, and dielectric studies in the de Vries
      smectic A (SmA) phase of organosiloxane derivatives exhibit features surprisingly
      different from that of a conventional SmA phase. The switching data show a double
      peak profile, characteristic of an antiferroelectric (AF) structure. A model with
      the adjacent smectic layers having an AF-like arrangement and no global tilt
      correlation is proposed. Observed in molecules with differential interactions
      between the two termini, these findings have wide ramifications in understanding
      the minimum layer shrinkage of such systems.

PMID- 19392484
TI  - Polarizable ions at interfaces.
AB  - A nonperturbative theory is presented which allows us to calculate the solvation
      free energy of polarizable ions near water-vapor and water-oil interfaces. The
      theory predicts that larger halogen anions are adsorbed at the interface, while
      the alkali metal cations are repelled from it. The density profiles calculated
      theoretically are similar to those obtained using molecular dynamics simulations
      with polarizable force fields.

PMID- 19392485
TI  - Inversion of band patterns in spherical tumblers.
AB  - Bidisperse granular mixtures in spherical tumblers segregate into three bands:
      one at each pole and one at the equator. For low fill levels, large particles are
      at the equator; for high fill levels, the opposite occurs. Segregation is robust,
      though the transition depends on fill level, particle size, and rotational speed.
      Discrete element method simulations reproduce surface patterns and reveal
      internal structures. Particle trajectories show that small particles flow farther
      toward the poles than large particles in the upstream portion of the flowing
      layer for low fill levels leading to a band of small particles at each pole. The
      opposite occurs for high fill levels, though more slowly.

PMID- 19392486
TI  - Cooling and aggregation in wet granulates.
AB  - Wet granular materials are characterized by a defined bond energy in their
      particle interaction such that breaking a bond implies an irreversible loss of a
      fixed amount of energy. Associated with the bond energy is a nonequilibrium
      transition, setting in as the granular temperature falls below the bond energy.
      The subsequent aggregation of particles into clusters is shown to be a self
      similar growth process with a cluster size distribution that obeys scaling. In
      the early phase of aggregation the clusters are fractals with D{f}=2, for later
      times we observe gelation. We use simple scaling arguments to derive the
      temperature decay in the early and late stages of cooling and verify our results
      with event-driven simulations.

PMID- 19392487
TI  - Funnel landscape and mutational robustness as a result of evolution under thermal
      noise.
AB  - Using a statistical-mechanical model of spins, the evolution of phenotype
      dynamics is studied. Configurations of spins and their interaction J represent
      the phenotype and genotype, respectively. The fitness for selection of J is given
      by the equilibrium spin configurations determined by a Hamiltonian with J under
      thermal noise. The genotype J evolves through mutational changes under selection
      pressure to raise its fitness value. From Monte Carlo simulations we find that
      the frustration around the target spins disappears for J evolved under
      temperature beyond a certain threshold. The evolved Js give the funnel-like
      dynamics, which is robust to noise and also to mutation.

PMID- 19392488
TI  - Vesicles in Poiseuille flow.
AB  - Blood microcirculation critically depends on the migration of red cells towards
      the flow centerline. We identify theoretically the ratio of the inner over the
      outer fluid viscosities lambda as a key parameter. At low lambda, the vesicle
      deforms into a tank-treading ellipsoid shape far away from the flow centerline.
      The migration is always towards the flow centerline, unlike drops. Above a
      critical lambda, the vesicle tumbles or breaths and migration is suppressed. A
      surprising coexistence of two types of shapes at the centerline, a bulletlike and
      a parachutelike shape, is predicted.

PMID- 19392489
TI  - Amplification of tension in branched macromolecules.
AB  - We propose a method for the design of branched macromolecules that are capable of
      building up high tension ( approximately nN) in their covalent bonds without
      applying an external force. The tension is self-generated due to repulsion
      between branches and depends on the molecular architecture leading to
      amplification and focusing of tension in specific bonds. The simplest
      architecture is a pom-pom composed of a linear spacer and two z-arm stars at its
      ends resulting in z-fold tension amplification. Adsorption of those
      macromolecules on a substrate results in further increase in tension as compared
      to molecules in solution.

PMID- 19392490
TI  - Dynamics of polymer decompression: expansion, unfolding, and ejection.
AB  - The dynamics of polymer decompression from a compact state to swollen
      conformation can be formally described as nonlinear diffusion. We discuss two
      basic examples: (i) the expansion, or unfolding from a compact state, and (ii)
      the ejection of a compressed polymer through a pore. The problem can be solved
      exactly for case (i), but not for case (ii). Even in such situations, a scheme
      called uniform approximation is shown to be useful to get a physical insight
      involved. Its application to case (ii) is able to account for conflicting
      numerical data in a consistent way.

PMID- 19392491
TI  - Comment on "turbulence-condensate interaction in two dimensions".

PMID- 19392493
TI  - Comment on "melting line of hydrogen at high pressures".

PMID- 19392495
TI  - Comment on "reciprocal relations for nonlinear coupled transport".

PMID- 19392497
TI  - Comment on "ab initio electronic and optical properties of the N-V- center in
      diamond".

PMID- 19392499
TI  - Optimal control of a qubit coupled to a non-Markovian environment.
AB  - A central challenge for implementing quantum computing in the solid state is
      decoupling the qubits from the intrinsic noise of the material. We investigate
      the implementation of quantum gates for a paradigmatic, non-Markovian model: a
      single-qubit coupled to a two-level system that is exposed to a heat bath. We
      systematically search for optimal pulses using a generalization of the novel open
      systems gradient ascent pulse engineering algorithm. Next to the known optimal
      bias point of this model, there are optimal pulses which lead to high-fidelity
      quantum operations for a wide range of decoherence parameters.

PMID- 19392500
TI  - Extreme tunability of interactions in a 7Li Bose-Einstein condensate.
AB  - We use a Feshbach resonance to tune the scattering length a of a Bose-Einstein
      condensate of 7Li in the |F=1,mF=1> state. Using the spatial extent of the
      trapped condensate, we extract a over a range spanning 7 decades from small
      attractive interactions to extremely strong repulsive interactions. The shallow
      zero crossing in the wing of the Feshbach resonance enables the determination of
      a as small as 0.01 Bohr radii. Evidence of the weak anisotropic magnetic dipole
      interaction is obtained by comparison with different trap geometries for small a.

PMID- 19392501
TI  - Tuning the gap of a superconducting flux qubit.
AB  - We experimentally demonstrate the in situ tunability of the minimum energy
      splitting (gap) of a superconducting flux qubit by means of an additional flux
      loop. Pulses applied via a local control line allow us to tune the gap over a
      range of several GHz on a nanosecond time scale. The strong flux sensitivity of
      the gap (up to approximately 0.7 GHz/mPhi0) opens up the possibility to create
      different types of tunable couplings that are effective at the degeneracy point
      of the qubit. We investigate the dependence of the relaxation time and the Rabi
      frequency on the qubit gap.

PMID- 19392502
TI  - Randomized benchmarking and process tomography for gate errors in a solid-state
      qubit.
AB  - We present measurements of single-qubit gate errors for a superconducting qubit.
      Results from quantum process tomography and randomized benchmarking are compared
      with gate errors obtained from a double pi pulse experiment. Randomized
      benchmarking reveals a minimum average gate error of 1.1+/-0.3% and a simple
      exponential dependence of fidelity on the number of gates. It shows that the
      limits on gate fidelity are primarily imposed by qubit decoherence, in agreement
      with theory.

PMID- 19392503
TI  - Superfluid heat conduction and the cooling of magnetized neutron stars.
AB  - We report on a new mechanism for heat conduction in the neutron star crust. We
      find that collective modes of superfluid neutron matter, called superfluid
      phonons, can influence heat conduction in magnetized neutron stars. They can
      dominate the heat conduction transverse to the magnetic field when the magnetic
      field B> approximately 10(13) G. At a density of rho approximately 10(12)-10(14)
      g/cm3, the conductivity due to superfluid phonons is significantly larger than
      that due to lattice phonons and is comparable to electron conductivity when the
      temperature approximately 10(8) K. This new mode of heat conduction can limit the
      surface anisotropy in highly magnetized neutron stars. Cooling curves of
      magnetized neutron stars with and without superfluid heat conduction could show
      observationally discernible differences.

PMID- 19392504
TI  - Towards loop quantum gravity without the time gauge.
AB  - The Hamiltonian formulation of the Holst action is reviewed and it provides a
      solution of second-class constraints corresponding to a generic local Lorentz
      frame. Within this scheme the form of rotation constraints can be reduced to a
      Gauss-like one by a proper generalization of Ashtekar-Barbero-Immirzi
      connections. This result emphasizes that the loop quantum gravity quantization
      procedure can be applied when the time-gauge condition does not stand.

PMID- 19392505
TI  - Exciting gauge field and gravitons in brane-antibrane annihilation.
AB  - In this Letter we point out the inevitability of an explosive production of gauge
      field and gravity wave during an open string tachyon condensation in a
      cosmological setting, in an effective field theory model. We will be particularly
      studying a toy model of brane-antibrane inflation in a warped throat where
      inflation ends via tachyon condensation. We point out that a tachyonic
      instability helps fragmenting the homogeneous tachyon and excites gauge field and
      contributes to the stress-energy tensor which also feeds into the gravity waves.

PMID- 19392507
TI  - Supersymmetric Higgs bosons in weak boson fusion.
AB  - We compute the complete supersymmetric next-to-leading-order corrections to the
      production of a light Higgs boson in weak-boson fusion. The size of the
      electroweak corrections is of similar order as the next-to-leading-order
      corrections in the standard model. The supersymmetric QCD corrections turn out to
      be significantly smaller than expected and than their electroweak counterparts.
      These corrections are an important ingredient to a precision analysis of the
      (supersymmetric) Higgs sector at the LHC, either as a known correction factor or
      as a contribution to the theory error.

PMID- 19392509
TI  - Hypersharp resonant capture of neutrinos as a laboratory probe of the Planck
      length.
AB  - The 18.6 keV antineutrino (nue) line from the two-body decay of 3H in crystals
      can be emitted with a natural width because of motional averaging by lattice
      vibrations despite the very long lifetime of 3H and contrary to commonly held
      views of linewidths in such a case. It can be resonantly captured in 3He with
      geometrical cross section sigma approximately 10(-17) cm2. Using its hypersharp
      sensitivity DeltaE/E approximately 10(-29) and the method of "time-filtered"
      resonance, the basic energy width approximately 10(-24) eV expected of the 3H
      state can be measured to test if ultimate nuclear widths are limited by the
      Planck length rather than time-energy uncertainty.

PMID- 19392511
TI  - Dispersion gammaZ-box correction to the weak charge of the proton.
AB  - We consider elastic scattering of electrons off a proton target. The parity
      violating (PV) asymmetry arises at leading order in alpha due to interference of
      gamma and Z exchange. The radiative corrections to this leading mechanism were
      calculated in the literature and included in experimental analyses, except for
      gammaZ-box and cross-box contributions. We present here a dispersion calculation
      of these corrections in forward kinematics. We demonstrate that at the GeV
      energies of current PV experiments, such corrections are not suppressed by the
      small vector weak charge of the electron, as occurs in the atomic parity
      violation. Our results suggest that the current theoretical uncertainty in the
      analysis of the QWEAK experiment might be substantially underestimated, and more
      accurate accounts of the dispersion corrections are needed in order to interpret
      the PV data.

PMID- 19392506
TI  - Evidence for the decay Bs0-->Ds(*)Ds(*) and a measurement of
      DeltaGammasCP/Gammas.
AB  - We search for the semi-inclusive process Bs0-->Ds(*)Ds(*) using 2.8 fb(-1) of pp
      collisions at sqrt[s]=1.96 TeV recorded by the D0 detector operating at the
      Fermilab Tevatron Collider. We observe 26.6+/-8.4 signal events with a
      significance above background of 3.2 standard deviations yielding a branching
      ratio of B(Bs0-->Ds(*)Ds(*))=0.035+/-0.010(stat.)+/-0.011(syst.). Under certain
      theoretical assumptions, these double-charm final states saturate CP-even
      eigenstates in the Bs0 decays resulting in a width difference of
      DeltaGammasCP/Gammas=0.072+/-0.021(stat.)+/-0.022(syst.).

PMID- 19392514
TI  - Shell Erosion and Shape Coexistence in (16)43S27.
AB  - We report on the g-factor measurement of the first isomeric state in (16)43S27
      [Ex=320.5(5) keV, T1/2=415(5) ns, and g=0.317(4)]. The 7/2- spin-parity of the
      isomer and the intruder nature of the ground state of the nucleus are
      experimentally established for the first time, providing direct and unambiguous
      evidence of the collapse of the N=28 shell closure in neutron-rich nuclei. The
      shell model, beyond the mean-field and semiempirical calculations, provides a
      very consistent description of this nucleus showing that a well deformed prolate
      and quasispherical states coexist at low energy.

PMID- 19392515
TI  - Search for the pygmy dipole resonance in 68Ni at 600 MeV/nucleon.
AB  - The gamma decay from Coulomb excitation of 68Ni at 600 MeV/nucleon on a Au target
      was measured using the RISING setup at the fragment separator of GSI. The 68Ni
      beam was produced by a fragmentation reaction of 86Kr at 900 MeV/nucleon on a 9Be
      target and selected by the fragment separator. The gamma rays produced at the Au
      target were measured with HPGe detectors at forward angles and with BaF2
      scintillators at backward angles. The measured spectra show a peak centered at
      approximately 11 MeV, whose intensity can be explained in terms of an enhanced
      strength of the dipole response function (pygmy resonance). Such pygmy structure
      has been predicted in this unstable neutron-rich nucleus by theory.

PMID- 19392517
TI  - Attosecond synchronization of high-order harmonics from midinfrared drivers.
AB  - The group delay dispersion, also known as the attochirp, of high-order harmonics
      generated in gases has been identified as the main intrinsic limitation to the
      duration of Fourier-synthesized attosecond pulses. Theory implies that the
      attochirp, which is inversely proportional to the laser wavelength, can be
      decreased at longer wavelength. Here we report the first measurement of the
      wavelength dependence of the attochirp using an all-optical, in situ method [N.
      Dudovich, Nature Phys. 2, 781 (2006)10.1038/nphys434]. We show that a 2 microm
      driving wavelength reduces the attochirp with respect to 0.8 microm at comparable
      intensities.

PMID- 19392516
TI  - Coherent terahertz echo of tunnel ionization in gases.
AB  - We study tunnel ionized electron wave packet dynamics during the initial
      transition from a gas to a plasma by detecting the terahertz radiation emitted in
      the process. Experimental and theoretical results show that much of the observed
      radiation is due to coherent buildup of bremsstrahlung released during the first
      electron-atom collision. Coherent control of the tunnel ionization process
      combined with ab initio modeling provides a real-time view of the initial stages
      of the formation of a laser-induced plasma and allows us to fully understand this
      important source of terahertz radiation.

PMID- 19392518
TI  - Complementary media invisibility cloak that cloaks objects at a distance outside
      the cloaking shell.
AB  - Based on the concept of complementary media, we propose an invisibility cloak
      operating at a finite frequency that can cloak an object with a prespecified
      shape and size within a certain distance outside the shell. The cloak is
      comprised of a dielectric core and an "antiobject" embedded inside a negative
      index shell. The cloaked object is not blinded by the cloaking shell since it
      lies outside the cloak. Full-wave simulations in two dimensions have been
      performed to verify the cloaking effect.

PMID- 19392508
TI  - Direct CP, lepton flavor, and isospin asymmetries in the decays B-->K(*)l+l-.
AB  - We measure branching fractions and integrated rate asymmetries for the rare
      decays B-->K(*)l+l-, where l+l- is either e+e- or micro+micro-, using a sample of
      384x10(6) BB events collected with the BABAR detector at the PEP-II e+e-
      collider. We find no evidence for direct CP or lepton-flavor asymmetries.
      However, for dilepton masses below the J/psi resonance, we find evidence for
      unexpectedly large isospin asymmetries in both B-->Kl+l- and B-->K*l+l- which
      differ, respectively, by 3.2sigma and 2.7sigma, including systematic
      uncertainties, from the standard model expectations.

PMID- 19392519
TI  - Density of states and extinction mean free path of waves in random media:
      dispersion relations and sum rules.
AB  - We establish a fundamental relationship between the averaged local density of
      states and the extinction mean free path of waves propagating in random media.
      From the principle of causality and the Kramers-Kronig relations, we show that
      both quantities are connected by dispersion relations and are constrained by a
      frequency sum rule. The results should be helpful in the analysis of wave
      transport through complex media and in the design of materials with specific
      transport properties.

PMID- 19392520
TI  - Three-dimensional metamaterials with an ultrahigh effective refractive index over
      a broad bandwidth.
AB  - The authors introduce a general mechanism, based on electrostatic and
      magnetostatic considerations, for designing three-dimensional isotropic
      metamaterials that possess an enhanced refractive index over an extremely large
      frequency range. The mechanism allows nearly independent control of effective
      electric permittivity and magnetic permeability without the use of resonant
      elements.

PMID- 19392521
TI  - Optical polarization modulation and gain anisotropy in an electrically injected
      spin laser.
AB  - The effects of spin-induced gain anisotropy on output polarization and threshold
      current reduction of electrically pumped spin-polarized lasers have been studied.
      Analytical forms of these parameters are derived by considering diffusive
      transport from the spin injector to the active region. The calculated values of
      the parameter are in excellent agreement with values obtained from measurements
      made at 200 K on an InAs/GaAs quantum dot spin-polarized vertical cavity surface
      emitting laser. Electrical modulation of the output polarization of the laser is
      demonstrated with a peak modulation index of 0.6.

PMID- 19392522
TI  - Composition relation between gap solitons and Bloch waves in nonlinear periodic
      systems.
AB  - We show with numerical computation and analysis that Bloch waves, at either the
      center or edge of the Brillouin zone, of a one dimensional nonlinear periodic
      system can be regarded as infinite chains composed of fundamental gap solitons
      (FGSs). This composition relation between Bloch waves and FGSs leads us to
      predict that there are n families of FGSs in the nth band gap of the
      corresponding linear periodic system, which is confirmed numerically.
      Furthermore, this composition relation can be extended to construct a class of
      solutions similar to Bloch waves but with multiple periods.

PMID- 19392523
TI  - Local capacitor model for plasmonic electric field enhancement.
AB  - We present a local capacitor model that enables a simple yet quantitatively
      accurate description of lightning rod effect in nanoplasmonics. A notion of
      lambda-zone capacitance is proposed and applied to predict the strongly induced
      electric field by a light source near nanoscale metal edges such as metal tip or
      metal gap. The enhancement factor, calculated from the local capacitor model,
      shows excellent agreement with more rigorous results. The lambda-zone capacitor
      allows a blockwise treatment of nano-optical devices and constitutes a basic
      element of optical nanocircuits.

PMID- 19392510
TI  - Search for high-mass resonances decaying to dimuons at CDF.
AB  - We present a search for high-mass neutral resonances using dimuon data
      corresponding to an integrated luminosity of 2.3 fb(-1) collected in pp[over ]
      collisions at sqrt[s]=1.96 TeV by the CDF II detector at the Fermilab Tevatron.
      No significant excess above the standard model expectation is observed in the
      dimuon invariant-mass spectrum. We set 95% confidence level upper limits on
      sigmaBR(pp-->X-->micromicro), where X is a boson with spin-0, 1, or 2. Using
      these cross section limits, we determine lower mass limits on sneutrinos in R
      parity-violating supersymmetric models, Z' bosons, and Kaluza-Klein gravitons in
      the Randall-Sundrum model.

PMID- 19392524
TI  - Influence of porosity on Rayleigh-Taylor instabilities in reaction-diffusion
      systems.
AB  - We analyze the effect of porosity in a porous medium on hydrodynamic
      instabilities in reaction-diffusion fronts. We use an experimental device to
      create an effective two-dimensional porous medium which is vertically orientated.
      In this system the molecular diffusion coefficients and the acid autocatalysis of
      the chlorite-tetrathionate reaction satisfy the appropriate conditions to produce
      a chemical front that advances through the cell leading to the products
      overlaying the reactants. The reactants have a lower density than the products
      and therefore a buoyantly unstable front develops. To evaluate the influence of
      the porosity on the formation and propagation of such instabilities, media with
      different porosities were used in the experiments. The amplitude of the
      instability is found to reduce as the porosity of the medium is decreased. For
      sufficiently small porosity, the instability can almost disappear leading to a
      planar front.

PMID- 19392525
TI  - Avalanches and non-Gaussian fluctuations of the global velocity of imbibition
      fronts.
AB  - We present an experimental study of the global velocity V(t) of a viscous fluid
      interface during forced-flow imbibition in a disordered medium. Our high
      resolution setup shows that the fronts display an intermittent behavior signature
      of a burstlike dynamics, with power-law distributed avalanches. When measured at
      scales comparable to the correlation length, velocity fluctuations follow an
      asymmetric non-Gaussian distribution, whose skewness increases with decreasing
      measuring window and/or injection flow rate, offering the effective number of
      degrees of freedom probed in our experiment.

PMID- 19392513
TI  - Search for anomalous top-quark couplings with the D0 detector.
AB  - Anomalous Wtb couplings modify the angular correlations of the top-quark decay
      products and change the single top-quark production cross section. We present
      limits on anomalous top-quark couplings by combining information from W boson
      helicity measurements in top-quark decays and anomalous coupling searches in the
      single top-quark final state. We set limits on right-handed vector couplings as
      well as left-handed and right-handed tensor couplings based on about 1 fb(-1) of
      data collected by the D0 experiment.

PMID- 19392527
TI  - Random changes of flow topology in two-dimensional and geophysical turbulence.
AB  - We study the two-dimensional (2D) stochastic Navier-Stokes (SNS) equations in the
      inertial limit of weak forcing and dissipation. The stationary measure is
      concentrated close to steady solutions of the 2D Euler equations. For such
      inertial flows, we prove that bifurcations in the flow topology occur either by
      changing the domain shape, the nonlinearity of the vorticity-stream-function
      relation, or the energy. Associated with this, we observe bistable behavior in
      SNS with random changes from dipoles to unidirectional flows. The theoretical
      explanation being very general, we infer the existence of similar phenomena in
      experiments and in some regimes of geophysical flows.

PMID- 19392528
TI  - Wave-particle interactions in electron acoustic waves in pure ion plasmas.
AB  - Electron acoustic waves (EAW) with a phase velocity less than twice the plasma
      thermal velocity are observed on pure ion plasma columns. At low excitation
      amplitudes, the EAW frequencies agree with theory, but at moderate excitation the
      EAW is more frequency variable than typical Langmuir waves, and at large
      excitations resonance is observed over a broad range. Laser induced fluorescence
      measurements of the wave-coherent ion velocity distribution show phase reversals
      and wave-particle trapping plateaus at +/-vph, as expected, and corroborate the
      unusual role of kinetic pressure in the EAW.

PMID- 19392512
TI  - Measurement of the lifetime of the Bc+/- meson in the semileptonic decay channel.
AB  - Using approximately 1.3 fb(-1) of data collected by the D0 detector between 2002
      and 2006, we measure the lifetime of the Bc+/- meson in the Bc-/+-->J/psimicro+/
      +X final state. A simultaneous unbinned likelihood fit to the J/psi+micro
      invariant mass and lifetime distributions yields a signal of 881+/-80(stat)
      candidates and a lifetime measurement of tau(Bc+/-)=0.448(-0.036)(+0.038)(stat)+/
      0.032(syst) ps.

PMID- 19392526
TI  - Particle segregation and dynamics in confined flows.
AB  - Nonlinearity in finite-Reynolds-number flow results in particle migration
      transverse to fluid streamlines, producing the well-known "tubular pinch effect"
      in cylindrical pipes. Here we investigate these nonlinear effects in highly
      confined systems where the particle size approaches the channel dimensions.
      Experimental and numerical results reveal distinctive dynamics, including complex
      scaling of lift forces with channel and particle geometry. The unique behavior
      described in this Letter has broad implications for confined particulate flows.

PMID- 19392529
TI  - Laser-driven shock acceleration of ion beams from spherical mass-limited targets.
AB  - We report on experimental studies of ion acceleration from spherical targets of
      diameter 15 microm irradiated by ultraintense (1x10(20) W/cm2) pulses from a 20
      TW Ti:sapphire laser system. A highly directed proton beam with plateau-shaped
      spectrum extending to energies up to 8 MeV is observed in the laser propagation
      direction. This beam arises from acceleration in a converging shock launched by
      the laser, which is confirmed by 3-dimensional particle-in-cell simulations. The
      temporal evolution of the shock-front curvature shows excellent agreement with a
      two-dimensional radiation pressure model.

PMID- 19392530
TI  - Nucleation of gold nanoparticle superclusters from solution.
AB  - Measurements of the solubility curve of a quasi-monodisperse gold nanoparticle
      solution are given. Temperature quenches from the one-phase to the two-phase
      regime yielded superclusters of the nanoparticle solid phase with sizes that
      depended on the quench depth. Classical nucleation theory was used to describe
      these sizes using a value of the surface tension for the nanoparticle solid phase
      of 0.042 erg/cm2. This value is consistent with molecule size scaling of the
      surface tension. In total these results show that suspensions of nanoparticles
      act like molecular solutions.

PMID- 19392531
TI  - Detection of buried microstructures by nonlinear light scattering spectroscopy.
AB  - Many processes in chemistry and physics rely on the structure, growth or change
      of material buried in solids. The impenetrable surrounding medium often prohibits
      the study of such material in situ. Nonlinear light scattering can be used to
      observe the internal structure of a crystalline state embedded inside another
      solid state. Vibrational sum frequency scattering patterns of polymer
      microspheres, consisting of both amorphous and crystalline material, reveal the
      size of the buried microstructure and the optical components of the second-order
      susceptibility of the material. The vibrational spectra reveal the molecular
      structure.

PMID- 19392532
TI  - Sufficient conditions for thermal rectification in hybrid quantum structures.
AB  - We analytically identify sufficient conditions for manifesting thermal
      rectification in two-terminal junctions, including a subsystem connected to two
      reservoirs, within the quantum master equation formalism. We recognize two
      classes of rectifiers. In type A rectifiers, the reservoirs' energy structure is
      dissimilar. In type B rectifiers, the baths are identical but include particles
      whose statistics differ from that of the subsystem, to which they asymmetrically
      couple. Our study applies to various hybrid junctions including metals,
      dielectrics, and spins.

PMID- 19392533
TI  - Atomistic simulation of field enhanced oxidation of Al (100) beyond the mott
      potential.
AB  - Molecular dynamics simulations employing dynamic charge transfer between atoms
      indicate a significantly enhanced rate of Al(100) oxidation by O2 and O at 300 K
      in the presence of an electric field. Increasing the electric field
      (approximately 10(7) V/cm) drives the surface chemisorbed oxygen to the vacancy
      sites in the oxide interior leading to dramatic density and stoichiometry
      improvements of the grown ultrathin oxide film. The associated oxidation kinetics
      enhancement due to the applied electric field is postulated to arise from the
      activation barrier lowering at electrostatic potentials approaching the Mott
      potential and beyond, leading to a dramatically increased ion migration through
      oxide film. The results are of significance to understanding mechanisms of early
      stage oxide growth as well as technologies utilizing ultrathin oxides.

PMID- 19392534
TI  - Solidification velocities in deeply undercooled silver.
AB  - We measure the solidification velocity of pure Ag as a function of undercooling
      temperature from the melting point (Tm=1235 K) to 0.6Tm using ultrafast, pump
      probe laser experiments. The thickness of the liquid layer, while it solidifies,
      is measured using optical third harmonic generation. We show that velocity
      reaches a maximum value at 0.85Tm, and then remains nearly constant with
      additional undercooling. These results contradict simple collision-limited
      models, but they are in good agreement with molecular dynamics simulations
      presented here, which show that the crystallization velocity depends weakly on
      temperature from 0.85Tm to less than approximately 0.1Tm.

PMID- 19392535
TI  - Atomic-resolution imaging with a sub-50-pm electron probe.
AB  - Using a highly coherent focused electron probe in a fifth-order aberration
      corrected transmission electron microscope, we report on resolving a crystal
      spacing less than 50 pm. Based on the geometrical source size and residual
      coherent and incoherent axial lens aberrations, an electron probe is calculated,
      which is theoretically capable of resolving an ideal 47 pm spacing with 29%
      contrast. Our experimental data show the 47 pm spacing of a Ge 114 crystal imaged
      with 11%-18% contrast at a 60%-95% confidence level, providing the first direct
      evidence for sub-50-pm resolution in annular dark-field scanning transmission
      electron microscopy imaging.

PMID- 19392536
TI  - Two pathways for water interaction with oxygen adatoms on TiO2(110).
AB  - Scanning tunneling microscopy and density functional theory studies show that
      oxygen adatoms (Oa), produced during O2 exposure of reduced TiO2(110) surfaces,
      alter the water dissociation and recombination chemistry through two distinctive
      pathways. Depending on whether H2O and Oa are on the same or adjacent Ti4+ rows,
      Oa facilitates H2O dissociation and proton transfer to form a terminal hydroxyl
      pair, positioned along or across the Ti4+ row, respectively. The latter process
      has not been reported previously, and it starts from a "pseudodissociated" state
      of water. In both pathways, the reverse H transfer results in H2O reformation and
      O scrambling, as manifested by an apparent along- or across-row motion of Oa's.

PMID- 19392537
TI  - Direct observation and theory of trajectory-dependent electronic energy losses in
      medium-energy ion scattering.
AB  - The energy spectrum associated with scattering of 100 keV H+ ions from the
      outermost few atomic layers of Cu(111) in different scattering geometries
      provides direct evidence of trajectory-dependent electronic energy loss.
      Theoretical simulations, combining standard Monte Carlo calculations of the
      elastic scattering trajectories with coupled-channel calculations to describe
      inner-shell ionization and excitation as a function of impact parameter,
      reproduce the effects well and provide a means for far more complete analysis of
      medium-energy ion scattering data.

PMID- 19392538
TI  - Role of atomic multiplets in the electronic structure of rare-earth
      semiconductors and semimetals.
AB  - We present a study of the effects of strong correlations in rare-earth pnictides,
      in which localized 4f states simultaneously retain atomiclike character and
      strongly influence the free-electron-like valence electron states. Using erbium
      arsenide as our example, we use a modern implementation of dynamical mean-field
      theory to obtain the atomic multiplet structure of the Er3+ 4f shell, as well as
      its unusually strong coupling to the electronic Fermi surfaces; these types of
      behavior are not correctly described within conventional electronic-structure
      methods. We are then able to explain the long-standing theoretical question of
      the quasisaturation of magnetization in an applied magnetic field, and to obtain
      the first quantitative agreement with experimental Shubnikov-de Haas frequencies
      of the Fermi-surface sheets.

PMID- 19392539
TI  - Dynamics of Trion formation in InxGa1-xAs quantum wells.
AB  - We show a double path mechanism for the formation of charged excitons (trions);
      they are formed through bi- and trimolecular processes. This directly implies
      that both negatively and positively charged excitons coexist in a quantum well,
      even in the absence of excess carriers. The model is substantiated by time
      resolved photoluminescence experiments performed on a very high quality InxGa1
      xAs quantum well sample, in which the photoluminescence contributions at the
      energy of the trion and exciton and at the band edge can be clearly separated and
      traced over a broad range of times and densities. The unresolved discrepancy
      between the theoretical and experimental radiative decay time of the exciton in a
      doped semiconductor quantum well is explained by the same model.

PMID- 19392540
TI  - Quantized hyperfine field at an implanted micro+ site in PrPb3: interplay between
      localized f electrons and an interstitial charged particle.
AB  - The local effect of an interstitial hydrogenlike particle on localized f
      electrons was studied in PrPb3 by means of micro+ spin rotation and relaxation.
      Spontaneous micro+ spin precession with harmonic frequencies was observed for the
      first time in f electron compounds. We demonstrate that the signal is derived
      from a coupling between the micro+ spin and the hyperfine-enhanced nuclear spin
      of nearest neighbor (NN) 141Pr with Ising-like anisotropy. The signal also
      suggests a marked suppression of spin dynamics of the NN 141Pr in comparison with
      that of the bulk 141Pr. These facts strongly indicate modification of the f
      electronic state due to the interstitial charged particle.

PMID- 19392541
TI  - Adiabatic-connection fluctuation-dissipation density-functional theory based on
      range separation.
AB  - An adiabatic-connection fluctuation-dissipation theorem approach based on a range
      separation of electron-electron interactions is proposed. It involves a rigorous
      combination of short-range density-functional and long-range random phase
      approximations. This method corrects several shortcomings of the standard random
      phase approximation and it is particularly well suited for describing weakly
      bound van der Waals systems, as demonstrated on the challenging cases of the
      dimers Be2 and Ne2.

PMID- 19392542
TI  - Exciton storage in a nanoscale Aharonov-Bohm ring with electric field tuning.
AB  - We study analytically the optical properties of a simple model for an electron
      hole pair on a ring subjected to perpendicular magnetic flux and in-plane
      electric field. We show how to tune this excitonic system from optically active
      to optically dark as a function of these external fields. Our results offer a
      simple mechanism for exciton storage and readout.

PMID- 19392543
TI  - Spin-orbital singlet and quantum critical point on the diamond lattice: FeSc2S4.
AB  - We present a theory of spin and orbital physics in the A-site spinel compound
      FeSc2S4, which experimentally exhibits a broad "spin-orbital liquid" regime. A
      spin-orbital Hamiltonian is derived from a combination of microscopic
      consideration and symmetry analysis. We demonstrate a keen competition between
      spin-orbit interactions, which favor formation of a local "spin-orbital singlet,"
      and exchange, which favors magnetic and orbital ordering. Separating the spin
      orbital singlet from the ordered state is a quantum critical point. We argue that
      FeSc2S4 is close to this quantum critical point on the spin-orbital singlet side.
      The full phase diagram includes a commensurate-incommensurate transition within
      the ordered phase. A variety of comparisons to and suggestions for experiments
      are discussed.

PMID- 19392544
TI  - Intrinsic half-metallicity in modified graphene nanoribbons.
AB  - We perform first-principles calculations based on density functional theory to
      study quasi-one-dimensional edge-passivated (with hydrogen) zigzag graphene
      nanoribbons of various widths with chemical dopants, boron and nitrogen, keeping
      the whole system isoelectronic. The gradual increase in doping concentration
      takes the system finally to zigzag boron nitride nanoribbons (ZBNNRs). Our study
      reveals that for all doping concentrations the systems stabilize in
      antiferromagnetic ground states. Doping concentrations and dopant positions
      regulate the electronic structure of the nanoribbons, exhibiting both
      semiconducting and half-metallic behaviors as a response to the external electric
      field. Interestingly, our results show that ZBNNRs with a terminating polyacene
      unit exhibit half-metallicity irrespective of the ribbon width as well as applied
      electric field, opening a huge possibility in spintronics device applications.

PMID- 19392545
TI  - Direct evidence for the role of the madelung potential in determining the work
      function of doped organic semiconductors.
AB  - The work function of a model degenerately doped organic semiconductor p-doped
      poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) can be systematically
      tuned over an eV-wide range by exchanging excess matrix protons with spectator
      cations, without altering the organic semiconductor doping level or polaron
      density. Ultraviolet photoelectron spectroscopy reveals this to arise not from an
      interface dipole, but from a bulk effect due to a shift in the Madelung potential
      set up by the local counter- and spectator-ion structure at the polaron sites.
      Electrostatic modeling of this potential is in agreement with the observed shift
      in carrier energetics. The spectator cations also cause a systematic shift in
      electron-phonon coupling and carrier delocalization, as revealed by infrared and
      Raman phonon modes, and charge-modulated absorption, which can be related to
      disorder in this potential.

PMID- 19392546
TI  - Itinerant ferromagnetism in the electronic localization limit.
AB  - We present Hall effect, Rxy(H), and magnetoresistance, Rxx(H), measurements of
      ultrathin films of Ni, Co, and Fe with thicknesses varying between 0.2 and 8 nm
      and resistances between 1 MOmega and 100 Omega. Both measurements show that films
      having a resistance above a critical value RC, (thickness below a critical value,
      dC) show no signs of ferromagnetism. Ferromagnetism appears only for films with
      R<RC, where RC is material dependent. We raise the possibility that the reason
      for the absence of spontaneous magnetism is the suppression of itinerant
      ferromagnetism by electronic disorder in the strong localization regime.

PMID- 19392547
TI  - Edge states in graphene: from gapped flat-band to gapless chiral modes.
AB  - We study edge states in graphene systems where a bulk energy gap is opened by
      inversion symmetry breaking. We find that the edge bands dispersion can be
      controlled by potentials applied on the boundary with unit cell length scale.
      Under certain boundary potentials, gapless edge states with valley-dependent
      velocity are found, exactly analogous to the spin-dependent gapless chiral edge
      states in quantum spin Hall systems. The connection of the edge states to bulk
      topological properties is revealed.

PMID- 19392548
TI  - Nondegenerate metallic States on Bi(114): a one-dimensional topological metal.
AB  - The (114) surface of the semimetal Bi is found to support a quasi-one
      dimensional, metallic surface state. As required by symmetry, the state is
      degenerate along the Gamma-Y line of the surface Brillouin zone with a highest
      binding energy of approximately 150 meV. In the Gamma-X direction the degeneracy
      is lifted by the strong spin-orbit splitting in Bi, as directly shown by spin
      resolved photoemission. This results in a Fermi contour consisting of two closely
      separated, parallel lines of opposite spin direction. It is argued that similar
      states on related insulators would give rise to a one-dimensional quantum spin
      Hall effect.

PMID- 19392549
TI  - Anomalous doping effects on charge transport in graphene nanoribbons.
AB  - We present first-principles calculations of quantum transport in chemically doped
      graphene nanoribbons with a width of up to 4 nm. The presence of boron and
      nitrogen impurities is shown to yield resonant backscattering, whose features are
      strongly dependent on the symmetry and the width of the ribbon, as well as the
      position of the dopants. Full suppression of backscattering is obtained on the pi
      pi* plateau when the impurity preserves the mirror symmetry of armchair ribbons.
      Further, an unusual acceptor-donor transition is observed in zigzag ribbons.
      These unconventional doping effects could be used to design novel types of
      switching devices.

PMID- 19392550
TI  - Cooling carbon nanotubes to the phononic ground state with a constant electron
      current.
AB  - We present a quantum theory of cooling of a mechanical resonator using back
      action with a constant electron current. The resonator device is based on a
      doubly clamped nanotube, which mechanically vibrates and acts as a double quantum
      dot for electron transport. Mechanical vibrations and electrons are coupled
      electrostatically using an external gate. The fundamental eigenmode is cooled by
      absorbing phonons when electrons tunnel through the double quantum dot. We
      identify the regimes in which ground-state cooling can be achieved for realistic
      experimental parameters.

PMID- 19392551
TI  - Abrupt rotation of the Rashba spin to the direction perpendicular to the surface.
AB  - The polarization vector of the Rashba spin, which must be parallel to the two
      dimensional (2D) plane in an ideal system, is found to change abruptly and
      definitely to the direction perpendicular to the surface at the K point of the
      Brillouin zone of a real hexagonal system, the Tl/Si(111)-(1x1) surface. This
      finding obtained experimentally by angle-resolved and spin-resolved photoemission
      measurements is fully confirmed by a first-principles theoretical calculation. We
      found that the abrupt rotation of the Rashba spin is simply understood by the 2D
      symmetry of the hexagonal structure.

PMID- 19392552
TI  - Tunneling between edge states in a quantum spin Hall system.
AB  - We analyze a quantum spin Hall device with a point contact connecting two of its
      edges. The contact supports a net spin tunneling current that can be probed
      experimentally via a two-terminal resistance measurement. We find that the low
      bias tunneling current and the differential conductance exhibit scaling with
      voltage and temperature that depend nonlinearly on the strength of the electron
      electron interaction.

PMID- 19392553
TI  - Thermoelectric and magnetothermoelectric transport measurements of graphene.
AB  - The conductance and thermoelectric power (TEP) of graphene is simultaneously
      measured using a microfabricated heater and thermometer electrodes. The sign of
      the TEP changes across the charge neutrality point as the majority carrier
      density switches from electron to hole. The gate dependent conductance and TEP
      exhibit a quantitative agreement with the semiclassical Mott relation. In the
      quantum Hall regime at a high magnetic field, quantized thermopower and Nernst
      signals are observed and are also in agreement with the generalized Mott
      relation, except for strong deviations near the charge neutrality point.

PMID- 19392554
TI  - Fermi surface and order parameter driven vortex lattice structure transitions in
      twin-free YBa2Cu3O7.
AB  - We report on small-angle neutron scattering studies of the intrinsic vortex
      lattice (VL) structure in detwinned YBa2Cu3O7 at 2 K, and in fields up to 10.8 T.
      Because of the suppressed pinning to twin-domain boundaries, a new distorted
      hexagonal VL structure phase is stabilized at intermediate fields. It is
      separated from a low-field hexagonal phase of different orientation and
      distortion by a first-order transition at 2.0(2) T that is probably driven by
      Fermi surface effects. We argue that another first-order transition at 6.7(2) T,
      into a rhombic structure with a distortion of opposite sign, marks a crossover
      from a regime where Fermi surface anisotropy is dominant, to one where the VL
      structure and distortion is controlled by the order-parameter anisotropy.

PMID- 19392555
TI  - Scanning tunneling spectroscopy and vortex imaging in the iron pnictide
      superconductor BaFe1.8Co0.2As2.
AB  - We present an atomic resolution scanning tunneling spectroscopy study of
      superconducting BaFe1.8Co0.2As2 single crystals in magnetic fields up to 9 T. At
      zero field, a single gap with coherence peaks at Delta=6.25 meV is observed in
      the density of states. At 9 and 6 T, we image a disordered vortex lattice,
      consistent with isotropic, single flux quantum vortices. Vortex locations are
      uncorrelated with strong-scattering surface impurities, demonstrating bulk
      pinning. The vortex-induced subgap density of states fits an exponential decay
      from the vortex center, from which we extract a coherence length xi=27.6+/-2.9 A,
      corresponding to an upper critical field Hc2=43 T.

PMID- 19392556
TI  - Quantum dynamics in a camelback potential of a dc SQUID.
AB  - We investigate a quadratic-quartic anharmonic oscillator formed by a potential
      well between two potential barriers. We realize this novel potential with a dc
      SQUID at near-zero current bias and flux bias near half a flux quantum. Escape
      out of the central well can occur via tunneling through either of the two
      barriers. We find good agreement with a generalized double-path macroscopic
      quantum tunneling theory. We also demonstrate an "optimal line" in current and
      flux bias along which the oscillator, which can be operated as a phase qubit, is
      insensitive to decoherence due to low-frequency current fluctuations.

PMID- 19392557
TI  - Role of the antiferromagnetic bulk spin structure on exchange bias.
AB  - The cooling field dependence of the exchange bias field in
      ferromagnet/antiferromagnet (FM/AF) multilayers demonstrates that the bulk AF
      spin structure plays a crucial role on the origin of exchange bias. FM/AF/FM
      trilayers were designed to eliminate any interlayer exchange coupling between the
      FM slabs. By choosing the magnetic cooling field, the AF is ordered below its
      Neel temperature with the FM layers fully saturated either parallel or
      antiparallel to each other. The significant difference in the exchange bias field
      between these two cooling configurations confirms that exchange bias cannot be a
      purely interfacial effect and that the bulk AF moments play a significant role in
      pinning the uncompensated spins at the AF/FM interface. This experiment also
      demonstrates that the mechanism responsible for coercivity enhancement has a
      different origin and is independent of the process that gives rise to exchange
      bias.

PMID- 19392558
TI  - Generalized spin-glass relaxation.
AB  - Spin relaxation close to the glass temperature of CuMn and AuFe spin glasses is
      shown, by neutron spin echo, to follow a generalized exponential function which
      explicitly introduces hierarchically constrained dynamics and macroscopic
      interactions. The interaction parameter is directly related to the normalized
      Tsallis nonextensive entropy parameter q and exhibits universal scaling with
      reduced temperature. At the glass temperature q=5/3 corresponding, within
      Tsallis' q statistics, to a mathematically defined critical value for the onset
      of strong disorder and nonlinear dynamics.

PMID- 19392559
TI  - Renormalization group for treating 2D coupled arrays of continuum 1D systems.
AB  - We study the spectrum of two dimensional coupled arrays of continuum one
      dimensional systems by wedding a density matrix renormalization group procedure
      to a renormalization group improved truncated spectrum approach. To illustrate
      the methodology, we study the spectrum of large arrays of coupled quantum Ising
      chains. We demonstrate explicitly that the method can treat the various regimes
      of chains, in particular, the three dimensional Ising ordering transition the
      chains undergo as a function of interchain coupling.

PMID- 19392560
TI  - Spin accumulation with spin-orbit interaction.
AB  - Spin accumulation is a crucial but imprecise concept in spintronics. In metal
      based spintronics it is characterized in terms of semiclassical distribution
      functions. In semiconductors with a strong spin-orbit coupling the spin
      accumulation is interpreted as a superposition of coherent eigenstates. Both
      views can be reconciled by taking into account the electron-electron interaction:
      a sufficiently strong self-consistent exchange field reduces a spin accumulation
      to a chemical potential difference between the two spin bands even in the
      presence of spin-orbit coupling. We demonstrate the idea on a clean two
      dimensional electron gas by showing how the exchange field protects a spin
      accumulation from dephasing and introduces an easy-plane anisotropy.

PMID- 19392561
TI  - Electric field induced by dynamical change of dipolar configurations in
      ferromagnets.
AB  - An analytical expression for the electric field, Eint, induced by any dynamical
      change of dipolar configuration is derived for ferromagnets. Effective
      Hamiltonian simulations are further conducted to realistically compute such field
      in an asymmetric permalloy ring. It is found that Eint mostly consists of short
      pulses that are correlated with the rapid temporal change of the magnetic
      toroidal moment in this low-dimensional ferromagnet, thus providing macroscopic
      information about the dynamical change of magnetic vortices. Discussion about the
      connection between Eint and some electric fields recently mentioned in the
      literature is also provided.

PMID- 19392562
TI  - Self-organized patterns of macroscopic quantum tunneling in molecular magnets.
AB  - We study low temperature resonant spin tunneling in molecular magnets induced by
      a field sweep with account of dipole-dipole interactions. Numerical simulations
      uncovered formation of self-organized patterns of the magnetization and of the
      ensuing dipolar field that provide resonant conditions inside a finite volume of
      the crystal. This effect is robust with respect to disorder and should be
      relevant to the dynamics of the magnetization steps observed in molecular
      magnets.

PMID- 19392563
TI  - Measurements of the neutron cross sections of hydrogen and deuterium in H2O-D2O
      mixtures using the deep inelastic neutron-scattering technique.
AB  - We investigated the neutron cross sections of hydrogen and deuterium by means of
      the deep inelastic neutron-scattering technique in H2O-D2O mixtures. The interest
      in this work was to examine the anomalous behavior in the hydrogen neutron cross
      section reported in the past in similar experiments that raised a yet unsettled
      controversy. The measurements were made at the Bariloche pulsed neutron source
      (Argentina) in pure H2O and D2O, with mixtures of molar concentrations of
      deuterium of xD=0.3 and 0.4, at room temperature, under the same experimental
      conditions as the former experiments. The results are in good agreement with the
      standard cross sections and are incompatible with the anomalies pointed out.

PMID- 19392564
TI  - Direct evidence of interlevel exciton transitions mediated by single phonons in a
      semiconductor quantum dot using resonance fluorescence spectroscopy.
AB  - Using resonance fluorescence, we investigate how acoustic phonons mediate
      couplings between multiple electronic levels in a semiconductor quantum dot. We
      show the first direct evidence of population up-conversion in a single quantum
      dot, which we attribute to absorption of single acoustic phonons. Moreover,
      through a rate equation analysis, we find that below 20 K such single-phonon
      mediated couplings between the exciton ground state and the first excited state
      are primarily responsible for decoherence of the exciton quantum state.

PMID- 19392565
TI  - Externally mode-matched cavity quantum electrodynamics with charge-tunable
      quantum dots.
AB  - We present coherent reflection spectroscopy on a charge and dc Stark tunable
      quantum dot embedded in a high-quality and externally mode-matched microcavity.
      The addition of an exciton to a single-electron-charged quantum dot forms a trion
      that interacts with the microcavity just below the strong-coupling regime of
      cavity quantum electrodynamics. Such an integrated, monolithic system is a
      crucial step towards the implementation of scalable hybrid quantum-information
      schemes that are based on an efficient interaction between a single photon and a
      confined electron spin.

PMID- 19392566
TI  - Long-time tails and cage effect in driven granular fluids.
AB  - We study the velocity autocorrelation function of a driven granular fluid in the
      stationary state in three dimensions. As the critical volume fraction of the
      glass transition in the corresponding elastic system is approached, we observe
      pronounced cage effects in the velocity autocorrelation function as well as a
      strong decrease of the diffusion constant, depending on the inelasticity. At
      moderate densities the velocity autocorrelation function is shown to decay
      algebraically in time, like t(-3/2), if momentum is conserved locally, and like
      t(-1), if momentum is not conserved by the driving. A simple scaling argument
      supports the observed long-time tails.

PMID- 19392568
TI  - Cross-modulated amplitudes and frequencies characterize interacting components in
      complex systems.
AB  - The dynamics of complex systems is characterized by oscillatory components on
      many time scales. To study the interactions between these components we analyze
      the cross modulation of their instantaneous amplitudes and frequencies,
      separating synchronous and antisynchronous modulation. We apply our novel
      technique to brain-wave oscillations in the human electroencephalogram and show
      that interactions between the alpha wave and the delta or beta wave oscillators
      as well as spatial interactions can be quantified and related with physiological
      conditions (e.g., sleep stages). Our approach overcomes the limitation to
      oscillations with similar frequencies and enables us to quantify directly
      nonlinear effects such as positive or negative frequency modulation.

PMID- 19392567
TI  - Charge transport in proteins probed by resonant photoemission.
AB  - The degrees of charge localization in the highest occupied and lowest unoccupied
      molecular orbitals (HOMO and LUMO) of the bacterial surface layer protein of
      Bacillus sphaericus NCTC 9602 were studied by resonant photoemission. In
      agreement with a charge transport hopping mechanism that involves torsional
      motions of the peptide backbone, the lifetime of electrons excited into the LUMO
      was found to be approximately 100 fs.

PMID- 19392569
TI  - Comment on "Quantum key distribution with classical Bob".

PMID- 19392571
TI  - Comment on "Near-edge X-ray absorption fine-structure investigation of graphene".
AB  - A Comment on the Letter by D. Pacile et al., Phys. Rev. Lett. 101, 066806
      (2008)10.1103/PhysRevLett.101.066806. The authors of the Letter offer a Reply.

PMID- 19392573
TI  - The influence of a continuing education program on the image interpretation
      accuracy of rural radiographers.
AB  - INTRODUCTION: In regional, rural and remote clinical practice, radiographers work
      closely with medical members of the acute care team in the interpretation of
      radiographic images, particularly when no radiologist is available. However, the
      misreading of radiographs by non-radiologist physicians has been shown to be the
      most common type of clinical error in the emergency department. Further, in
      Australia few rural radiographers are specifically trained to interpret and
      report on images. This study aimed to evaluate the accuracy of a group of rural
      radiographers in interpreting musculoskeletal plain radiographs, and to assess
      the effectiveness of continuing education (CE) in improving their accuracy within
      a short time frame. METHODS: Following ethics approval, 16 rural radiographers
      were recruited to the study. At inception a purpose-designed 'test-object' of 25
      cases compiled by a radiologist was used to assess image interpretation accuracy.
      The cases were categorised into three grades of complexity. The radiographers
      entered their answers on a structured radiographer opinion form (ROF) that had
      three levels of response - 'general opinion', 'observations' and 'open comment'.
      Subsequent to base-line testing, the radiographers participated in a CE program
      aimed at improving their image interpretation skills. After a 4 month period they
      were re-tested using the same methodology. The ROFs were scored by the
      radiologist and the pooled results analysed for statistically significant changes
      at all ROF levels and grades of complexity. RESULTS: While for the small number
      of less complex grade 1 cases there was no change in image interpretation
      accuracy, for the more numerous and more complex grade 2 and grade 3 cases there
      was a statistically significant improvement at the 'general opinion' and
      'observation' levels (paired t-test, p < 0.05). Also, with the exception of the
      small sample of grade 1 cases, the proportion of cases correctly interpreted by
      the radiographers decreased as the ROF level, and therefore the amount of detail
      required, increased. CONCLUSIONS: This study had a number of methodological
      limitations but the results suggest that short-term, intensive CE programs can
      improve the ability of radiographers to accurately interpret plain
      musculoskeletal radiographic examinations. Similar, larger scale initiatives such
      as this could help reduce the risk of misdiagnosis in acute care settings,
      especially in the absence of a radiologist. However, radiographers' ability to
      use radiological vocabulary needs improvement. The complementary role that exists
      between radiographers and other members of the acute care team should be nurtured
      and developed in the context of declining numbers of radiologists, particularly
      in non-metropolitan areas. Intensive, short-term training in image interpretation
      may target junior medical officers, GPs and critical care nurse practitioners, as
      well as radiographers.

PMID- 19392574
TI  - RNA interference-based gene therapy for successful treatment of rheumatoid
      arthritis.
AB  - BACKGROUND: RNA interference (RNAi) is a powerful endogenous process initiated by
      short double-stranded RNAs, which results in sequence-specific
      posttranscriptional gene silencing. The possibility of blocking the expression of
      any protein carries huge expectations for potential therapeutic applications in a
      wide range of diseases. For clinical development, however, the use of RNAi-based
      therapeutics has to overcome major obstacles, mainly targeted delivery and safety
      issues. OBJECTIVE/METHODS: In this short review, we provide an overview of
      specifications for RNAi-based gene therapy in rheumatoid arthritis (RA) and
      discuss recent progresses in the development of efficient silencing, focusing on
      expression of short hairpin RNAs. RESULTS/CONCLUSIONS: Combining advances in RNAi
      methodology with gene therapy technology opens avenues for rapid applications to
      RA.

PMID- 19392575
TI  - Dendritic cells: therapy and imaging.
AB  - BACKGROUND: Dendritic cells (DCs) play a major role in cell-mediated
      immunotherapy. In this approach, DCs are isolated from cancer patients and pulsed
      with exogenous and specific tumor antigens in vitro, and the antigen-loaded DCs
      are then transferred to the hosts to enhance the immune response against tumor
      targets. Clinical observations and animal studies have shown that tumors can
      elicit immune responses caused by tumor infiltration of T-lymphocytes. Several
      pilot clinical trials have been recently conducted using this strategy for
      treating several types of cancers. OBJECTIVE: To optimize DC-based therapy with
      emerging molecular imaging techniques. METHODS: A review of the most current
      literature on DCs and imaging work. RESULTS/CONCLUSION: The translational
      application of DC-based therapy can be supported greatly through molecular
      imaging. New discoveries on DC migration and behavior in vivo will lead to new
      advances in the treatment of a broad range of cancers.

PMID- 19392576
TI  - From lab to bedside: emerging clinical applications of thymosin alpha 1.
AB  - BACKGROUND: Thymosin alpha(1) (Talpha(1)), a synthetic version of a thymic
      derived biological response modifier was the first of the thymosins in clinical
      use. Talpha(1) is approved in over 35 countries for the treatment of hepatitis B
      and C, and as an immune stimulant and adjuvant. Talpha(1) is also in late-stage
      clinical testing in the United States and Europe for hepatitis C and stage IV
      melanoma. OBJECTIVE/METHODS: Novel applications and other recently completed
      trials point to much broader clinical applications of Talpha(1) in the treatment
      of life-threatening and chronic diseases, and are the subject of this review.
      RESULT/CONCLUSIONS: The most recent reports of clinical trials with Talpha(1) are
      pointing to important, hitherto unrecognized, applications in a number of
      diseases and disorders, including septic shock, acute respiratory distress
      syndrome, peritonitis, acute cytomegalovirus infection, TB, severe acute
      respiratory syndrome, and lung infections in critically ill patients. It is also
      emerging as a promising chemoprotection agent in patients undergoing
      chemotherapy.

PMID- 19392577
TI  - Overcoming obstacles to develop effective and safe siRNA therapeutics.
AB  - BACKGROUND: RNA interference (RNAi) is a promising new therapeutic modality. By
      acting at the mRNA level, RNAi circumvents the druggability issue associated with
      many disease-driven genes. The lack of safe and effective methods to deliver RNAi
      therapeutics remains the primary technical hurdle that prevents full utilization
      of the potential of RNAi therapy. OBJECTIVE: To examine progress in the
      therapeutic RNAi field and highlight remaining hurdles for the development of
      RNAi therapeutics. METHODS: This review focuses on the design principles of
      delivery technologies that demonstrated target inhibition in vivo after systemic
      administration. CONCLUSION: Although many promising delivery technologies have
      been described, all current delivery platforms have limitations. However, using
      an optimal combination of disease indication, disease target and the most potent
      RNA trigger, it may be possible to advance RNAi therapeutics in the near term
      using an imperfect delivery vehicle. The availability of high-throughput assays
      to monitor/compare various delivery systems for their performance in vivo will be
      essential for programs that focus on siRNA delivery.

PMID- 19392578
TI  - Pneumococcal vaccines for allergic airways diseases.
AB  - BACKGROUND: Asthma is a common global health problem. Environmental exposures
      such as bacteria may protect against asthma development. OBJECTIVE: This review
      aims to examine the possible protective role of pneumococcal infection and
      vaccination in asthma. METHODS: A review of known experimental biology and human
      epidemiology relating to asthma and pneumococcal infection was performed.
      RESULTS: Pneumococcal infection can modulate components of allergic airways
      disease such as airways hyperresponsiveness and airway eosinophilia. Exposure to
      killed pneumococcus can reproduce these effects and the mechanism may involve
      control by T regulatory cells. CONCLUSIONS: Pneumococcal immunoregulatory therapy
      is a potentially important approach to asthma management that requires further
      evaluation in well-designed research studies.

PMID- 19392582
TI  - Sizing evaporative aerosols: the "man with too many watches" dilemma.

PMID- 19392579
TI  - Naproxcinod, a new cyclooxygenase-inhibiting nitric oxide donator (CINOD).
AB  - BACKGROUND: COX-inhibiting nitric oxide donators (CINODs) are a new class of
      drugs that combine the actions of the parent COX inhibitor with nitric oxide
      (NO), with the aim of reducing potential toxicity of the parent drug, while
      maintaining its analgesic and anti-inflammatory effects. AZD3582 (Naproxcinod) is
      the first in the class of CINODs. OBJECTIVE/METHODS: To review the effects of NO
      donation, CINODS in general and naproxen in osteoarthritis (OA), based on
      literature in PubMed. RESULTS: In preclinical and human studies, this drug
      produced similar analgesic and anti-inflammatory effects to its parent naproxen,
      with improved gastrointestinal safety in OA patients. The results of recent
      clinical trials, which were designed to study effects on blood pressure, are
      expected shortly, after peer-review. CONCLUSIONS: As naproxen is considered the
      safest COX inhibitor choice from a cardiovascular perspective, AZD3582 has the
      potential to become a new drug treatment in patients with OA, in whom pain and
      function are not controlled by the use of analgesics.

PMID- 19392583
TI  - Evolution of evaporative understanding within nebulizer standards.

PMID- 19392584
TI  - Predicting in vivo deposition in vitro.

PMID- 19392585
TI  - Reconciliation of Cascade Impaction during Wet Nebulization.
AB  - Cascade impaction is an important tool for measuring aerosol distributions from
      wet nebulizers; however, results vary depending on laboratory and technique. The
      focus of this study was to reconcile the contribution of particle evaporation to
      these reported differences. To measure the effect of evaporation, we compared
      aerosol distributions from circuits ventilated with humidified air, ambient air,
      and a nonventilated, standing cloud circuit using low-flow cascade impaction (1.0
      L/min). Aerosol distributions were similar for the humidified/ventilated and
      standing cloud models [mass median aerodynamic diameter (MMAD) 3.4 microm, and
      3.6 microm Aero-Eclipse, 5.8 and 5.1 microm Misty-Neb, 3.8 and 3.2 microm Pari LC
      Plus]. In the ventilated/ambient air model, smaller particle sizes were measured
      (2.2 microm AeroEclipse, 2.4 microm Misty-Neb, 2.1 microm Pari LC Plus).
      Techniques of cascade impaction significantly affected measured aerosol
      distributions. MMAD were defined by nebulizer type and conditions of particle
      evaporation not by impactor. Aerosol mixing with ambient air caused evaporation
      and shrinkage of particles, and accounts for differences between laboratories.
      Patients breathing from nebulizers may entrain ambient air possibly affecting
      deposition.

PMID- 19392586
TI  - Aerodynamic characteristics of nebulized terbutaline sulphate using the Next
      Generation Impactor (NGI) and CEN method.
AB  - Characterization of the aerosolized dose emitted from a nebulized system can be
      determined using CEN (prEN13544-1) methodology and more recently with a Next
      Generation Impactor (NGI), but evaporative effects can influence the results. We
      have investigated these characteristics using different flows and cooling with
      the NGI and compared the results to the standard CEN method using two different
      nebulizer systems. The NGI was operated using flows of 15 and 30 L min(-1) at
      room (ROOM) temperature and immediately after cooling at 5 degrees C for 90 min
      (COLD). Two nebulizer systems, the Sidestream jet nebulizer (SIDE) and the
      Aeroneb Pro (AERO), were used to nebulize terbutaline sulphate respiratory
      solution. The CEN method was also used to provide the aerodynamic characteristics
      of the aerosolized dose from these two nebulizer systems. The mean (SD) mass
      median aerodynamic diameter (MMAD) using 15COLD, 15ROOM, 30COLD, 30ROOM, and CEN
      for AERO was 5.0(0.1), 4.1(0.3), 4.4(0.2), 2.0(0.3), and 3.0(1.1) microm,
      respectively, and 4.2(0.4), 2.6(0.4), 3.5(0.1), 1.7(0.1), and 3.2(0.3) microm for
      SIDE. The fine particle fraction (FPF), using the NGI, followed the expected
      trend associated with the corresponding MMAD values, ranging from 48.1 to 70.5%
      from AERO and 57.3 to 87.8% for SIDE. The mean FPF for AERO and SIDE using the
      CEN methodology was 72.5 and 63.6%. Overall there was a highly significant
      difference (p < 0.001) between the different operating conditions for the FPF and
      MMAD of both nebulizer systems. All methods revealed a significant difference
      between AERO and SIDE except CEN. Both nebulizer systems were prone to
      evaporation effects during in vitro testing. Cooling and using a slow flow
      minimizes evaporation effects with the NGI and should be adopted as the
      recommended compendial method. The CEN method provides different values to those
      of the NGI operating conditions and could not differentiate between the two
      nebulizers.

PMID- 19392587
TI  - Air humidity may influence the aerosol distribution of normal saline administered
      by closed or vented nebulizers operated continuously or dosimetrically.
AB  - In clinical practice the majority of inhaled agents require deposition in the
      most distant regions of the bronchial tree. Contrary to this, it is likely that
      morphine delivery in breathlessness and chronic cough should be directed to the
      tracheobronchial area. The aim of the present study was to assess how an
      environmental condition such as air humidity might influence the particle
      distribution of normal saline administered by closed or vented nebulizers
      operated continuously or dosimetrically. Aerosol generated as a saline solution
      was assessed for BCTSS (Bronchial Control Treatment System-Sidestream) and BCTS
      MC (Bronchial Control Treatment System-Micro Cirrus), together with two pneumatic
      delivery systems: Pneumatic Inhalation-Sidestream (PI-S) and Pneumatic Inhalation
      Micro Cirrus (PI-MC). To clarify the influence of humidity on the aerosol we
      introduced a fifth method, BCTS-S/C, which included a vented nebulizer operated
      continuously. The impact of different air humidity on the size of particles was
      examined. Only in the case of the vented methods (BCTS-S and BCTSS/C) of
      nebulization did air humidifying lead to a significant enlargement of particle
      size. Moreover, the mean particle size at 90% was almost twice as large with the
      use of BCTS-S than with BCTS-S/C. Our experiment demonstrated that ambient
      humidity has a greater effect on particle size with vented rather than nonvented
      nebulizers and the effect might be potentiated by the pulsative method of
      nebulization.

PMID- 19392588
TI  - Modifications to the subtemporal selective amygdalohippocampectomy using a
      minimal-access technique: seizure and neuropsychological outcomes.
AB  - OBJECT: The authors introduce a minimal-access subtemporal approach for selective
      resection of the amygdala and hippocampus in patients with temporal lobe epilepsy
      and describe seizure and neuropsychological outcomes. METHODS: Between October
      2003 and April 2007, 41 consecutive patients with intractable unilateral
      nonlesional temporal lobe epilepsy underwent image-guided subtemporal
      amygdalohippocampectomy. Baseline characteristics, preoperative evaluations, and
      seizure outcomes were assessed. Eighteen patients underwent pre- and
      postoperative neuropsychological testing for cognitive functioning, executive
      functioning, verbal and visual memory, and mood. RESULTS: Important aspects of
      the subtemporal approach include a low temporal keyhole craniotomy, use of image
      guidance, preservation of the tentorium, incision in the fusiform gyrus, and
      subpial, en bloc resection of the hippocampus. There were no deaths and no cases
      of significant postoperative morbidity. At 1 year, 29 of 36 patients (81%) were
      without seizures or auras. At 2 years, 17 of 23 (74%) patients were seizure- and
      aura-free. Detailed neuropsychological testing of language, memory, cognitive
      functioning, and executive functioning suggested that most patients exhibited
      either stability or improvement in their scores, regardless of language
      lateralization. CONCLUSIONS: A minimal-access subtemporal approach for
      amygdalohippocampectomy is an effective treatment for temporal lobe epilepsy
      yielding encouraging preliminary seizure and neuropsychological outcomes.

PMID- 19392590
TI  - Use of the h index in neurosurgery. Clinical article.
AB  - OBJECT: Assessing academic productivity through simple quantification may
      overlook key information, and the use of statistical enumeration of academic
      output is growing. The h index, which incorporates both the total number of
      publications and the citations of those publications, has been recently proposed
      as an objective measure of academic productivity. The authors used several tools
      to calculate the h index for academic neurosurgeons to provide a basis for
      evaluating publishing by physicians. METHODS: The h index of randomly selected
      academic neurosurgeons from a sample of one-third of the academic programs in the
      US was calculated using data from Google Scholar and from the Scopus database.
      The mean h index for each academic rank was determined. The h indices were also
      correlated with various other factors (such as time spent practicing
      neurosurgery, authorship position) to identify how these factors influenced the h
      index. The h indices were then compared with other citation statistics to
      evaluate the robustness of this metric. Finally, h indices were also calculated
      for a sampling of physicians in other medical specialties for comparison.
      RESULTS: As expected, the h index increased with academic rank and there was a
      statistically significant difference between each rank. A weighting based on
      position of authorship did not affect h indices. The h index was positively
      correlated with time since American Board of Neurological Surgery certification,
      and it was also correlated with other citation metrics. A comparison among
      medical specialties supports the assertion that h index values may not be
      comparable between fields, even closely related specialties. CONCLUSIONS: The h
      index appears to be a robust statistic for comparing academic output of
      neurosurgeons. Within the field of academic neurosurgery, clear differences of h
      indices between academic ranks exist. On average, an increase of the h index by 5
      appears to correspond to the next highest academic rank, with the exception of
      chairperson. The h index can be used as a tool, along with other evaluations, to
      evaluate an individual's productivity in the academic advancement process within
      the field of neurosurgery but should not be used for comparisons across medical
      specialties.

PMID- 19392589
TI  - Time course for autoregulation recovery following severe traumatic brain injury.
AB  - OBJECT: The aim of the present study was to evaluate the time course for cerebral
      autoregulation (AR) recovery following severe traumatic brain injury (TBI).
      METHODS: Thirty-six patients (27 males and 9 females, mean +/- SEM age 33 +/-
      15.1 years) with severe TBI underwent serial dynamic AR studies with leg cuff
      deflation as a stimulus, until recovery of the AR responses was measured.
      RESULTS: The AR was impaired (AR index < 2.8) in 30 (83%) of 36 patients on Days
      3-5 after injury, and in 19 individuals (53%) impairments were found on Days 9-11
      after the injury. Nine (25%) of 36 patients exhibited a poor AR response (AR
      index < 1) on postinjury Days 12-14, which eventually recovered on Days 15-23.
      Fifty-eight percent of the patients with a Glasgow Coma Scale score of 3-5, 50%
      of those with diffuse brain injury, 54% of those with elevated intracranial
      pressure, and 40% of those with poor outcome had no AR recovery in the first 11
      days after injury. CONCLUSIONS: Autoregulation recovery after severe TBI can be
      delayed, and failure to recover during the 2nd week after injury occurs mainly in
      patients with a lower Glasgow Coma Scale score, diffuse brain injury, elevated
      ICP, or unfavorable outcome. The finding suggests that perfusion pressure
      management should be considered in some of the patients for a period of at least
      2 weeks.

PMID- 19392591
TI  - Clinical and radiobiological advantages of single-dose stereotactic light-ion
      radiation therapy for large intracranial arteriovenous malformations. Technical
      note.
AB  - OBJECT: Radiation treatment of large arteriovenous malformations (AVMs) remains
      difficult and not very effective, even though seemingly promising methods such as
      staged volume treatments have been proposed by some radiation treatment centers.
      In symptomatic patients harboring large intracranial AVMs not amenable to
      embolization or resection, single-session high-dose stereotactic radiation
      therapy is a viable option, and the special characteristics of high-ionization
      density light-ion beams offer several treatment advantages over photon and proton
      beams. These advantages include a more favorable depth-dose distribution in
      tissue, an almost negligible lateral scatter of the beam, a sharper penumbra, a
      steep dose falloff beyond the Bragg peak, and a higher probability of vascular
      response due to high ionization density and associated induction of endothelial
      cell proliferation and/or apoptosis. Carbon ions were recently shown to be an
      effective treatment for skull-base tumors. Bearing that in mind, the authors
      postulate that the unique physical and biological characteristics of light-ion
      beams should convey considerable clinical advantages in the treatment of large
      AVMs. In the present meta-analysis the authors present a comparison between light
      ion beam therapy and more conventional modalities of radiation treatment with
      respect to these lesions. METHODS: Dose-volume histograms and data on peripheral
      radiation doses for treatment of large AVMs were collected from various radiation
      treatment centers. Dose-response parameters were then derived by applying a
      maximum likelihood fitting of a binomial model to these data. The present
      binomial model was needed because the effective number of crucial blood vessels
      in AVMs (the number of vessels that must be obliterated to effect a cure, such as
      large fistulous nidus vessels) is low, making the Poisson model less suitable. In
      this study the authors also focused on radiobiological differences between
      various radiation treatments. RESULTS: Light-ion Bragg-peak dose delivery has the
      precision required for treating very large AVMs as well as for delivering
      extremely sharp, focused beams to irregular lesions. Stereotactic light-ion
      radiosurgery resulted in better angiographically defined obliteration rates, less
      white-matter necrosis, lower complication rates, and more favorable clinical
      outcomes. In addition, in patients treated by He ion beams, a sharper dose
      response gradient was observed, probably due to a more homogeneous
      radiosensitivity of the AVM nidus to light-ion beam radiation than that seen when
      low-ionization-density radiation modalities, such as photons and protons, are
      used. CONCLUSIONS: Bragg-peak radiosurgery can be recommended for most large and
      irregular AVMs and for the treatment of lesions located in front of or adjacent
      to sensitive and functionally important brain structures. The unique physical and
      biological characteristics of light-ion beams are of considerable advantage for
      the treatment of AVMs: the densely ionizing beams of light ions create a better
      dose and biological effect distribution than conventional radiation modalities
      such as photons and protons. Using light ions, greater flexibility can be
      achieved while avoiding healthy critical structures such as diencephalic and
      brainstem nuclei and tracts. Treatment with the light ion He or Li is more
      suitable for AVMs <or= 10 cm(3), whereas treatment with the light ion Li, Be, or
      C may be more appropriate for larger AVMs. A binomial model based on the
      effective number of crucial vessels in the AVM may be used quite well to predict
      AVM obliteration probabilities for both small and large AVMs when therapies
      involving either photons or light ions are used.

PMID- 19392592
TI  - Feasibility of ventricular expansion postmortem: a novel laboratory model for
      neurosurgical training that simulates intraventricular endoscopic surgery.
AB  - OBJECT: Cadavers are often used in the teaching of various neurosurgical
      procedures. One aspect of this resource that has not been previously explored is
      the postmortem dilation of the ventricular system, which is often collapsed, for
      the purpose of training neurosurgeons in the use of intraventricular endoscopy.
      METHODS: Nine adult cadavers without a history of hydrocephalus or other known
      intracranial pathology were used for this study. Four specimens were obtained
      post embalming, and 5 specimens were fresh (time from death until the procedure <
      5 hours). In all cadavers catheters were placed into the lateral ventricles;
      saline and then air were injected into the ventricles through the catheters.
      Ventriculostomy sites were filled with rubber stoppers, and in fresh specimens,
      formal embalming was performed with cadavers in the Trendelenburg position.
      Lastly, serial horizontal sectioning of the cranium was performed in all cadavers
      to verify ventricular dilation. RESULTS: None of the 4 embalmed specimens were
      found to have ventriculomegaly following injection. However, this condition was
      found in 4 of the 5 fresh specimens. In the single fresh cadaver without
      ventriculomegaly, the cause of death had been massive intracranial subarachnoid
      hemorrhage, which distorted the ventricular system. This may have prevented
      cannulation of the ventricle and ventricular expansion in this specimen.
      CONCLUSIONS: The ventricular system of fresh human cadavers can be dilated
      postmortem. The method described herein may be useful to neurosurgical trainees
      or those trained neurosurgeons wishing to practice intraventricular endoscopy.

PMID- 19392593
TI  - Classification of trigeminal neuralgia: clinical, therapeutic, and prognostic
      implications in a series of 144 patients undergoing microvascular decompression.
AB  - OBJECT: Trigeminal neuralgia (TN) presents a diagnostic challenge because of the
      variety of symptoms, findings during microvascular decompression (MVD), and
      postsurgical outcomes observed among patients who suffer from this disorder.
      Recently, a new paradigm for classification of TN was proposed, based on the
      quality of pain. This study represents the first clinical analysis of this
      paradigm. METHODS: The authors analyzed 144 consecutive cases involving patients
      who underwent MVD for TN. Preoperative symptoms were classified into 1 of 2
      categories based on the preponderance of shocklike (Type 1 TN) or constant (Type
      2 TN) pain. Analysis of clinical characteristics, neurovascular pathology, and
      postoperative outcome was performed. RESULTS: Compared with Type 2 TN, Type 1 TN
      patients were older, were more likely to have right-sided symptoms, and reported
      a shorter duration of symptoms prior to evaluation. Previous treatment by
      percutaneous or radiosurgical procedures was not a predictor of symptoms,
      surgical findings, or outcome (p = 0.48). Type 1 TN was significantly more likely
      to be associated with arterial compression. Venous or no compression was more
      common among Type 2 TN patients (p < 0.01). Type 1 TN patients were also more
      likely to be pain-free immediately after surgery, and less likely to have a
      recurrence of pain within 2 years (p < 0.05). Although a subset of patients
      progressed from Type 1 to Type 2 TN over time, their pathological and prognostic
      profiles nevertheless resembled those of Type 1 TN. CONCLUSIONS: Type 1 and Type
      2 TN represent distinct clinical, pathological, and prognostic entities.
      Classification of patients according to this paradigm should be helpful to
      determine how best to treat patients with this disorder.

PMID- 19392594
TI  - Radiosurgery for intracranial hemangiopericytomas: outcomes after initial and
      repeat Gamma Knife surgery.
AB  - OBJECT: Intracranial hemangiopericytoma is a rare CNS tumor that exhibits a high
      incidence of local recurrence and distant metastasis. The purpose of this study
      was to evaluate the role of Gamma Knife surgery (GKS) in the management of
      intracranial hemangiopericytomas. METHODS: In a review of the University of
      Virginia radiosurgery database between 1989 and 2008, the authors found recurrent
      or residual hemangiopericytomas after resection in 21 patients in whom
      radiosurgery was performed to treat 28 discrete tumors. The median age of this
      population was 47 years (range 31-61 years) at the time of the initial GKS. Prior
      treatments included embolization (6), transcranial resection (39),
      transsphenoidal resection (2), and fractionated radiotherapy (8). The mean
      prescription and maximum radiosurgical doses to the tumors were 17.0 and 40.3 Gy,
      respectively. Repeat radiosurgery was used to treat 13 tumors. The median follow
      up period was 68 months (range 2-138 months). RESULTS: At last follow-up, local
      tumor control was demonstrated in 47.6% of the patients (10 of 21 patients) with
      hemangiopericytomas. Of the 28 tumors treated, 8 decreased in size on follow-up
      imaging (28.6%), 5 remained unchanged (17.9%), and 15 ultimately progressed
      (53.6%). The progression-free survival rates were 90, 60.3, and 28.7% at 1, 3,
      and 5 years after initial GKS. The progression-free survival rate improved to 95,
      71.5, and 71.5% at 1, 3, and 5 years after multiple GKS treatments. The 5-year
      survival rate after radiosurgery was 81%. Prior fractionated irradiation or
      radiosurgical prescription dose did not correlate with tumor control. In 4 (19%)
      of 21 patients extracranial metastases developed. CONCLUSIONS: Radiosurgery is a
      reasonable treatment option for recurrent hemangiopericytomas. Long-term close
      clinical and imaging follow-up is necessary because of the high probability of
      local recurrence and distant metastases. Repeat radiosurgery may be used to treat
      new or recurrent hemangiopericytomas over a long follow-up course.

PMID- 19392595
TI  - Trains of transcranial direct current stimulation antagonize motor cortex
      hypoexcitability induced by acute hemicerebellectomy.
AB  - OBJECT: The cerebellum is a key modulator of motor cortex activity, allowing both
      the maintenance and fine-tuning of motor cortex discharges. One elemental defect
      associated with acute cerebellar lesions is decreased excitability of the
      contralateral motor cortex, which is assumed to participate in deficits in
      skilled movements and considered a major defect in motor cortex properties. In
      the present study, the authors assessed the effect of trains of anodal
      transcranial direct current stimulation (tDCS), which elicits polarity-dependent
      shifts in resting membrane potentials. METHODS: Transcranial DCS countered the
      defect in motor cortex excitability contralaterally to the hemicerebellar
      ablation. RESULTS: The depression of both the H-reflex and F wave remained
      unchanged with tDCS, and cutaneomuscular reflexes remained unaffected.
      Transcranial DCS antagonized motor cortex hypoexcitability induced by high
      frequency stimulation of interpositus nucleus. CONCLUSIONS: The authors' results
      show that tDCS has the potential to modulate motor cortex excitability after
      acute cerebellar dysfunction. By putting the motor cortex at the appropriate
      level of excitability, tDCS might allow the motor cortex to become more reactive
      to the procedures of training or learning.

PMID- 19392597
TI  - Sensitivity of high-resolution three-dimensional magnetic resonance angiography
      and three-dimensional spoiled-gradient recalled imaging in the prediction of
      neurovascular compression in patients with hemifacial spasm.
AB  - OBJECT: Hemifacial spasm is a clinical syndrome caused by vascular compression of
      the facial nerve in the cerebellopontine angle, which can be relieved by surgical
      intervention. Advances in medical imaging technology allow for direct
      visualization of the offending blood vessels in hemifacial spasm and similar
      conditions (such as trigeminal neuralgia). The utility of high resolution 3D MR
      angiography and 3D spoiled-gradient recalled (SPGR) imaging sequences for
      surgical decision-making in hemifacial spasm, as measured by sensitivity,
      specificity, and positive and negative predictive values, has not been previously
      determined. METHODS: A retrospective review was undertaken of 23 patients with
      hemifacial spasm who underwent operations between January 2001 and December 2006
      at Oregon Health & Science University. All patients underwent preoperative high
      resolution 3D MR angiography and 3D SPGR imaging. The sensitivity of the SPGR
      imaging/MR angiography interpretation of neurovascular compression (NVC) by both
      a neurosurgeon and 2 neuroradiologists was determined in relation to the presence
      of actual NVC during surgery. RESULTS: All patients were found to have NVC at
      surgery. After review by a neurosurgeon and 2 neuroradiologists, imaging data
      from 19 of the 23 patients were evaluated. The neurosurgeon's interpretation had
      a sensitivity of 79% and a positive predictive value (PPV) of 100%. The first
      neuroradiologist's interpretation had a sensitivity of 21% with a PPV of 100%.
      Further interpretation by a blinded second neuroradiologist with expertise in MR
      imaging of hemifacial spasm and trigeminal neuralgia was conducted, and
      sensitivity was 59% and PPV was 100%. Specificity was not determined because
      there were no true negative cases. The negative predictive value was 0% for both
      the neurosurgeon's and neuroradiologists' evaluations. CONCLUSIONS: Although high
      resolution 3D MR angiography and 3D SPGR imaging was helpful in providing
      information about the anatomical relationship of cranial nerve VII and
      surrounding blood vessels, the authors determined that in the case of hemifacial
      spasm these types of imaging did not influence preoperative surgical
      decisionmaking.

PMID- 19392598
TI  - Characteristics of auras in patients undergoing temporal lobectomy.
AB  - OBJECT: Prior studies suggest that aura semiology may have localizing value.
      However, temporal lobe aura characteristics and response to surgery have not been
      studied in large patient series. METHODS: The authors retrospectively analyzed
      the case records of 182 patients undergoing temporal lobectomy for medically
      intractable epilepsy at a single institution. They analyzed the frequency and
      type of auras and seizures preoperatively, and at 3 months and 1 year after
      temporal lobectomy. Auras were divided into medial semiology (rising epigastric,
      olfactory/gustatory, experiential, and fear) and lateral semiology (auditory,
      somatosensory, and visual), or other. RESULTS: Of 182 patients, 150 were included
      in this study. The preoperative prevalence of auras was 77%. Multiple types of
      auras were present in 20% of patients. The most common aura was rising epigastric
      (26% of all auras). Postoperatively, auras were eliminated in 63% of patients at
      3 months and in 64% at 1 year. Seventy-seven patients (51%) were seizure-free and
      aura-free, 22 (15%) were seizure-free with auras, 26 (17%) had seizures but no
      auras, and 25 (17%) had seizures with auras. Despite having their auras
      eliminated, 6.7% of patients continued to have complex partial seizures. Lateral
      temporal auras were more than twice as likely as medial temporal auras to persist
      after surgery (p < 0.002). CONCLUSIONS: While the majority of patients in the
      authors' series became seizure- and aura-free, a significant minority still had
      persistent auras. Patients with lateral temporal auras appear to be at increased
      risk for having persistent postoperative auras. The discrepancy between aura and
      seizure outcomes results in a small group of patients having persistent seizures
      but losing their auras postoperatively.

PMID- 19392599
TI  - Effect of WT1 gene silencing on the tumorigenicity of human glioblastoma
      multiforme cells.
AB  - OBJECT: Wilms tumor 1 (WT1) is overexpressed in many human cancers, including
      glioblastoma multiforme (GBM). In another study, the authors showed that
      transient WT1 silencing increases the radiosensitivity of glioma cells. Studies
      of nonglioma cell lines have demonstrated that WT1 promotes cell proliferation
      and survival; however, this ability has not been rigorously analyzed in human
      GBM. METHODS: The authors tested the efficacy of 2 sequences of short hairpin RNA
      (shRNA) directed against WT1 in U251MG human GBM cells and found that 1 sequence
      was capable of stably silencing WT1 expression. They then evaluated the effect of
      WT1 silencing on cellular proliferation, invasion, and in vivo tumor formation.
      RESULTS: Stable WT1-shRNA expression significantly decreased the proliferation of
      U251MG cells in vitro as demonstrated by both an adenosine 5'-triphosphate-based
      viability assay and tritiated thymidine uptake. Furthermore, stable WT1 silencing
      caused significantly slower growth after the subcutaneous inoculation of tumor
      cells in the flanks of athymic nude mice and was associated with an increased
      latency period. CONCLUSIONS: Data in this study provide proof of the principle
      that downregulation of WT1 causes decreased tumorigenicity of a GBM cell line in
      vitro and in vivo and suggest that WT1 is a promising target for novel molecular
      GBM therapies, perhaps in combination with standard treatment modalities.

PMID- 19392600
TI  - Mesial temporal lobe epilepsy.

PMID- 19392601
TI  - William Henry Battle and Battle's sign: mastoid ecchymosis as an indicator of
      basilar skull fracture.
AB  - William Henry Battle (1855-1936) practiced medicine in England > 1 century ago
      and is primarily remembered for his description of ecchymosis over the mastoid,
      which indicates fracture of the skull base. Although Mr. Battle made many
      contributions to medicine, almost nothing exists in the literature regarding his
      life and findings, especially in regard to head injury. The following is a review
      of Battle's background and his contributions to medicine, specifically his
      observations associated with basilar skull fractures.

PMID- 19392602
TI  - Real-time myocardial perfusion contrast echocardiography and regional wall motion
      abnormalities after aneurysmal subarachnoid hemorrhage. Clinical article.
AB  - OBJECT: The pathophysiology of myocardial dysfunction after subarachnoid
      hemorrhage (SAH) remains unclear. Using myocardial real-time perfusion contrast
      echocardiography (RTP-CE), the authors evaluated microvascular function in
      patients with acute SAH. METHODS: Over a 15-month period, 10 patients with acute
      SAH and evidence of cardiac dysfunction were prospectively enrolled. The authors
      performed RTP-CE within 48 hours of SAH diagnosis. Wall motion and myocardial
      perfusion were evaluated in 16 left ventricle segments. Qualitative and
      quantitative RTP-CE analyses were conducted to compare patients with and without
      regional wall motion abnormalities (RWMAs). Follow-up RTP-CE at a mean of 53.7 +/
      43 days was undertaken in patients with baseline RWMAs. RESULTS: Ten patients
      with SAH and evidence of cardiac dysfunction were prospectively enrolled. There
      were 3 men and 7 women whose mean age was 63.5 +/- 10.1 years. The authors
      documented evidence of RWMAs in 6 patients. Normal perfusion was demonstrated by
      RTP-CE in all patients at baseline and follow-up, despite the presence of RWMAs.
      Compared with patients presenting with normal wall motion, in patients with RWMAs
      there was a trend for higher quantitative RTP-CE parameters, suggesting hyperemia
      with mean myocardial blood flow velocity (beta, s(-1)) of 1.08 +/- 0.61 (95% CI 0
      2.61) compared with 1.62 +/- 0.64 (95% CI 0.94-2.29) and myocardial blood flow (A
      x beta, dB/s) of 0.99 +/- 0.41 (95% CI 0-2.0) versus 1.63 +/- 0.86 (95% CI 0.72
      2.53). Follow-up RTP-CE was feasible in 3 patients with RWMAs. Regional systolic
      function was restored in those who completed follow-up. CONCLUSIONS: The authors
      found that RTP-CE readily evaluates microvascular function in patients with SAH.
      Wall motion and perfusion dissociation were observed. Quantitative RTP-CE showed
      a trend for microvascular hyperemia in patients with RWMAs, suggesting that post
      SAH myocardial dysfunction could occur in the absence of microvascular
      dysfunction.

PMID- 19392603
TI  - Management guided by brain tissue oxygen monitoring and outcome following severe
      traumatic brain injury.
AB  - OBJECT: The authors sought to describe changes in clinical management associated
      with brain tissue oxygen (PbO(2)) monitoring and how these changes affected
      outcomes and resource utilization. METHODS: The cohort study comprised 629
      patients admitted to a Level I trauma center with a diagnosis of severe traumatic
      brain injury over a period of 3 years. Hospital mortality rate, neurological
      outcome, and resource utilization of 123 patients who underwent both PbO(2) and
      intracranial pressure (ICP) monitoring were compared with the same measures in
      506 patients who underwent ICP monitoring only. The main outcomes were hospital
      mortality rate, functional independence at hospital discharge, duration of
      mechanical ventilation, hospital length of stay, and hospital cost. Multivariable
      regression with robust variance was used to estimate the adjusted differences in
      the main outcome measures between patient groups. The models were adjusted for
      patient age, severity of injury, and pathological features seen on head CT scan
      at admission. RESULTS: On average, patients who underwent ICP/PbO(2) monitoring
      were younger and had more severe injuries than patients who received ICP
      monitoring alone. Relatively more patients treated with PbO(2) monitoring
      received osmotic therapy, vasopressors, and prolonged sedation. After adjustment
      for baseline characteristics, the hospital mortality rate was, if anything,
      slightly higher in patients undergoing PbO(2)-guided management than in patients
      monitored with ICP only (adjusted mortality difference 4.4%, 95% CI -3.9 to 13%).
      Patients who underwent PbO(2)-guided management also had lower adjusted
      functional independence scores at hospital discharge (adjusted score difference 
      0.75, 95% CI -1.41 to -0.09). There was a 27% relative increase (95% CI 6-53%) in
      the median hospital length of stay when the PbO(2) group was compared with the
      ICP-only group. CONCLUSIONS: The mortality rate in patients with traumatic brain
      injury whose clinical management was guided by PbO(2) monitoring was not reduced
      in comparison with that in patients who received ICP monitoring alone. Brain
      tissue oxygen monitoring was associated with worse neurological outcome and
      increased hospital resource utilization.

PMID- 19392604
TI  - Surface-based facial scan registration in neuronavigation procedures: a clinical
      study.
AB  - OBJECT: Surface-based registration (SBR) with facial surface scans has been
      proposed as an alternative for the commonly used fiducial-based registration in
      image-guided neurosurgery. Recent studies comparing the accuracy of SBR and
      fiducial-based registration have been based on a few targets located on the head
      surface rather than inside the brain and have yielded contradictory conclusions.
      Moreover, no visual feedback is provided with either method to inform the surgeon
      about the estimated target registration error (TRE) at various target locations.
      The goals in the present study were: 1) to quantify the SBR error in a clinical
      setup, 2) to estimate the targeting error for many target locations inside the
      brain, and 3) to create a map of the estimated TRE values superimposed on a
      patient's head image. METHODS: The authors randomly selected 12 patients (8
      supine and 4 in a lateral position) who underwent neurosurgery with a commercial
      navigation system. Intraoperatively, scans of the patients' faces were acquired
      using a fast 3D surface scanner and aligned with their preoperative MR or CT head
      image. In the laboratory, the SBR accuracy was measured on the facial zone and
      estimated at various intracranial target locations. Contours related to different
      TREs were superimposed on the patient's head image and informed the surgeon about
      the expected anisotropic error distribution. RESULTS: The mean surface
      registration error in the face zone was 0.9 +/- 0.35 mm. The mean estimated TREs
      for targets located 60, 105, and 150 mm from the facial surface were 2.0, 3.2,
      and 4.5 mm, respectively. There was no difference in the estimated TRE between
      the lateral and supine positions. The entire registration procedure, including
      positioning of the scanner, surface data acquisition, and the registration
      computation usually required < 5 minutes. CONCLUSIONS: Surface-based registration
      accuracy is better in the face and frontal zones, and error increases as the
      target location lies further from the face. Visualization of the anisotropic TRE
      distribution may help the surgeon to make clinical decisions. The observed and
      estimated accuracies and the intraoperative registration time show that SBR using
      the fast surface scanner is practical and feasible in a clinical setup.

PMID- 19392605
TI  - Survival of mossy cells of the hippocampal dentate gyrus in humans with mesial
      temporal lobe epilepsy.
AB  - OBJECT: Hippocampal sclerosis can be identified in most patients with mesial
      temporal lobe epilepsy (TLE). Surgical removal of the sclerotic hippocampus is
      widely performed to treat patients with drug-resistant mesial TLE. In general,
      both epilepsy-prone and epilepsy-resistant neurons are believed to be in the
      hippocampal formation. The hilar mossy cells of the hippocampal dentate gyrus are
      usually considered one of the most vulnerable types of neurons. The aim of this
      study was to clarify the fate of mossy cells in the hippocampus in epileptic
      humans. METHODS: Of the 19 patients included in this study, 15 underwent temporal
      lobe resection because of drug-resistant TLE. Four patients were used as controls
      because they harbored tumors that had not invaded the hippocampus and they had
      experienced no seizures. Histological evaluation of resected hippocampal tissues
      was performed using immunohistochemistry. RESULTS: Mossy cells were identified in
      the control as well as the epileptic hippocampi by using cocaine- and amphetamine
      regulated transcript peptide immunohistochemistry. In most cases the number of
      mossy cells was reduced and thorny excrescences were smaller in the epileptic
      hippocampi than in controls; however, there was a significant loss of pyramidal
      cells and a partial loss of granule cells in the same epileptic hippocampi in
      which mossy cell loss was apparent. The loss of mossy cells could be correlated
      with the extent of hippocampal sclerosis, patient age at seizure onset, duration
      of epilepsy, and frequency of seizures. CONCLUSIONS: In many cases large numbers
      of mossy cells were present in the hilus of the dentate gyrus when most pyramidal
      neurons of the CA1 and CA3 areas of the Ammon's horn were lost, suggesting that
      mossy cells may not be more vulnerable to epileptic seizures than the hippocampal
      pyramidal neurons.

PMID- 19392606
TI  - Stroke-risk perception in women: getting the message out.

PMID- 19392607
TI  - Image-guided robotic interventions for breast biopsy and ablative therapies:
      challenges and opportunities.

PMID- 19392609
TI  - Neonatal outcomes in relation to timing of repeat cesarean delivery at term.
AB  - The increasing rates of repeat cesarean delivery necessitate, more than ever, the
      need to time deliveries to optimize neonatal outcomes. A recent large multicenter
      cohort study demonstrated that, contrary to current recommendations, a high
      proportion of elective cesarean deliveries in the USA are performed before 39
      weeks' gestation. These early deliveries are associated with a significant
      increase in several adverse neonatal events, including respiratory complications,
      treated hypoglycemia, newborn sepsis and admission to the neonatal intensive care
      unit. This, together with results of previous studies, supports the
      recommendation to delay elective delivery to 39 weeks' gestation. From the
      current data, it is uncertain whether delivery before 39 weeks' gestation with
      documented fetal lung maturity will prevent the increased neonatal morbidity.

PMID- 19392611
TI  - Adjuvant systemic therapy for older adults with early-stage breast cancer.
AB  - There is a relative paucity of evidence to guide the adjuvant therapy of breast
      cancer in older adults. Herein, we review data from relevant clinical trials and
      retrospective analyses that assess systemic therapies in older adults.
      Chemotherapy, endocrine therapy, HER2-directed agents and bisphosphonates in the
      adjuvant setting are discussed. Meta-analyses, such as the Oxford overview,
      suggest a decreasing benefit of chemotherapy with age. However, prospective
      trials do support a benefit from the addition of chemotherapy to endocrine
      therapy in older adults. In contrast to chemotherapy, the value of endocrine
      therapy appears to increase with age. In addition, available subset analyses
      suggest that the benefit from aromatase inhibitors relative to tamoxifen is
      independent of age. The use of HER2-directed therapy in older adults is
      challenged by the relatively low enrollment of this subset in prospective
      clinical trials. Nonetheless, the extent of enrollment may be proportional to the
      frequency of HER2 overexpression in this population. Finally, there are little
      data to support the use of adjuvant bisphosphonate therapy in older adults-
      ongoing prospective trials may address this issue. Each of the aforementioned
      therapeutic strategies will be augmented by efforts to personalize therapy for
      older adults. Clinical tools such as the geriatric assessment and biologic
      assays, such as the 21-gene recurrence score, may ultimately play a role in
      treatment algorithms for this unique demographic.

PMID- 19392610
TI  - Breast cancer diagnosis during pregnancy.
AB  - Breast cancer diagnosed during pregnancy is a challenging situation for the
      patient and her medical team. As women are delaying childbirth, the incidence is
      expected to increase. Most of the data surrounding the diagnosis and treatment of
      cancer during pregnancy is in case reports and small cohort studies. However, the
      data continues to expand regarding the safety of systemic treatments during the
      second and third trimesters for both the mother and the fetus. In this article,
      the use of diagnostic imaging, procedures, surgery and chemotherapy are reviewed
      as well as prognosis and future pregnancies after the treatment for breast
      cancer.

PMID- 19392612
TI  - Gestational diabetes mellitus: developments in diagnosis and treatment.
AB  - After many years of uncertainty regarding the true pathological nature of mild
      gestational diabetes and the possible benefits of treatment, the situation
      appears to have been resolved by the publication of the Australian Carbohydrate
      Intolerance Study in Pregnant Women (ACHOIS). It is now appropriate for obstetric
      units to review their treatment and screening programs for gestational diabetes
      mellitus. Furthermore, with the publication of the Metformin in Gestational
      Diabetes (MiG) trial, consideration should be given as to whether metformin
      should be the first choice when diet fails to maintain glycemic control.

PMID- 19392613
TI  - Trauma in the obstetrical patient.
AB  - Trauma complicates approximately 6-7% of all pregnancies and is associated with
      significant maternal and fetal morbidity and mortality. While the majority of
      trauma is minor, it is minor trauma that contributes to the majority of fetal
      mortality. Since virtually every organ system is affected anatomically and
      physiologically by pregnancy, it is important for healthcare providers who care
      for trauma victims to be aware of these changes. While assessment and
      resuscitation considers the existence of two patients, stabilization of the
      mother takes priority. Diagnostic and radiologic procedures should be used as
      indicated, with fetal exposure to radiation limited as much as possible.
      Management of the pregnant trauma victim requires a multidisciplinary approach in
      order to optimize outcome for mother and fetus. This review discusses the
      epidemiology, assessment and treatment of pregnant trauma patients and reviews
      areas where prevention efforts may be focused.

PMID- 19392614
TI  - Postpartum depression: an update.
AB  - Postpartum depression occurs in at least one in seven new mothers, usually within
      the first 6 months after delivery. By the time of onset of postpartum depression,
      the mother has usually long since been discharged from the maternity hospital.
      Early identification and treatment of these mothers reduces both maternal and
      infant suffering. Careful risk-benefit decision-making regarding various
      treatment options in the postpartum should be discussed with the mother. Risks of
      untreated depression include poor bonding with the infant, lack of self care,
      infant neglect and infanticide.

PMID- 19392615
TI  - Adenomyosis: new knowledge is generating new treatment strategies.
AB  - In the early days, all mucosal invasions of abdominal organs were considered to
      be one pathological condition of uncertain origin, termed adenomyoma. It was only
      in the 1920s that endometriosis and adenomyosis were clearly separated and it
      took approximately 80 years to put forward a new theory reunifying their
      pathogenesis. Today, identification of adenomyosis is carried out exclusively
      through vaginal ultrasonography and MRI. These techniques have made a careful
      evaluation of a distinct anatomical structure and the inner myometrial layers
      underlying the endometrium, termed the junctional zone, possible. Adenomyosis is
      characterized by a homogeneous thickening of this portion of the myometrium. When
      this hyperplasia is associated to an alteration of spiral arterioles'
      angiogenesis, then both adenomyosis and endometriosis may develop. Evidence is
      being accumulated that pre-eclampsia, fetal growth restriction and premature
      delivery may be linked, together representing a new, major obstetrical syndrome
      characterized by a modified uterine environment around the time of nidation. A
      dozen different medical or surgical techniques are utilized for the treatment of
      adenomyosis and novel approaches are being tested. These include use of
      inhibitors of angiogenesis that have been shown to cause reduced neo
      angiogenesis, a significant modification of gene expression and a decrease in the
      percentage of active lesions. Encouraging results have also been obtained with
      the levonorgestrel-releasing intrauterine system.

PMID- 19392616
TI  - Abnormal uterine bleeding: a focus on polycystic ovary syndrome.
AB  - Abnormal uterine bleeding imposes major medical, social and financial problems
      for women, their families and the health services. Abnormal uterine bleeding
      refers to the regularity, frequency, duration and volume of bleeding. Irregular
      menstrual bleeding is most common at the extremes of reproductive life, in the
      initial 12-18 months after menarche and 5-6 years before the menopause begins. In
      Australia, the estimated cost of investigating and managing heavy menstrual
      bleeding alone is approximately AUS $6 million per annum. This article addresses
      the common causes of irregular bleeding in pre- and peri-menopausal women and
      presents an investigational approach.

PMID- 19392617
TI  - Pelvic organ prolapse and relationship with skeletal integrity.
AB  - Health burden related to osteoporotic fractures in an aging female population far
      exceeds that imposed by other chronic disorders such as cardiovascular disease
      and breast cancer. Bone mineral density assessment and clinical risk factors
      provide independent insights into fracture risk in individuals. A finite list of
      clinical risk factors are identified as prognostic of fracture risk, namely among
      aging women, including low body mass, compromised reproductive physiology (e.g.,
      prolonged periods of amenorrhea and early menopause), parental and personal
      histories of fracture, and alcohol and tobacco use. Pelvic organ prolapse is a
      common gynecologic entity and a contributor to age-related morbidities. The
      purpose of this review is to communicate data identifying pelvic organ prolapse
      as another clinical risk factor for fracture risk in postmenopausal women and to
      increase the caregiver's vigilance in anticipating and instituting preventive
      care strategies to a population (i.e., postmenopausal women with clinically
      appreciable pelvic organ prolapse) that may be at an enhanced lifetime risk for
      skeletal fractures.

PMID- 19392619
TI  - High burden of staphylococcal disease in indigenous communities.

PMID- 19392620
TI  - Prolonged influenza virus infection during lymphocytopenia and frequent detection
      of drug-resistant viruses.
AB  - The factors that cause prolonged human influenza virus respiratory tract
      infection and determine its clinical impact and the development of drug-resistant
      viruses are unclear. During a 3-year period, symptomatic influenza virus
      excretion for 2 weeks was observed among 8 immunocompromised patients and found
      to be associated with lymphocytopenia at onset (8 of 8 patients) more often than
      with granulocytopenia (2 of 8 patients) or monocytopenia (2 of 8 patients). Six
      (75%) of 8 patients developed influenza lower respiratory tract infection (10
      episodes), and receipt of oseltamivir treatment was significantly associated with
      clinical improvement (8 of 8 episodes vs. 0 of 2 untreated episodes; P = .02).
      Complete viral clearance was strongly correlated with lymphocyte reconstitution
      (P = .04) but was never observed during the first 2 weeks after oseltamivir
      treatment. Neuraminidase inhibitor-resistant influenza viruses emerged in 2 (67%)
      of 3 patients eligible for resistance analysis. In conclusion, prolonged
      influenza virus infection was associated with lymphocytopenia, influenza lower
      respiratory tract infection, and frequent development of drug resistance during
      antiviral therapy. Clinical improvement in influenza lower respiratory tract
      infection is observed during oseltamivir treatment, but complete viral clearance
      is dependent on lymphocyte reconstitution, irrespective of receipt of antiviral
      medication.

PMID- 19392621
TI  - TNF and LTA gene, allele, and extended HLA haplotype associations with severe
      dengue virus infection in ethnic Thais.
AB  - Severe dengue virus (DENV) infection is characterized by a cascade of cytokine
      production, including the production of tumor necrosis factor-alpha (TNF-alpha)
      and lymphotoxin-alpha (LT-alpha). We have analyzed a variety of polymorphisms in
      the TNF and LTA genes of 435 ethnic Thais who had subclinical DENV infection,
      primary or secondary dengue fever (DF), or primary or secondary dengue
      hemorrhagic fever (DHF). The TNF -238A polymorphism marking the TNF-4,LTA-3
      haplotype occurred in a significantly greater number of patients with secondary
      DHF (20 [15.2%] of 132) than patients with secondary DF (7 [4.1%] of 169) (P <
      .001; P corrected by use of Bonferroni adjustment, .022; odds ratio, 4.13 [95%
      confidence interval, 1.59-11.17]). In a subset of patients, the LTA-3 haplotype
      was associated with in vivo intracellular production of LT-alpha and TNF-alpha
      during the acute viremic phase of infection. Two extended human major
      histocompatibility complex (MHC) haplotypes containing TNF-4 and LTA-3, together
      with HLA-B48, HLA-B57, and HLA-DPB1*0501, were detected only in patients with
      secondary DHF. These observations indicate that polymorphism in functionally
      distinct MHC-encoded proteins contributes to the risk of developing severe
      secondary DENV infection and warrants further investigation.

PMID- 19392622
TI  - Community-associated strains of methicillin-resistant Staphylococcus aureus and
      methicillin-susceptible S. aureus in indigenous Northern Australia: epidemiology
      and outcomes.
AB  - BACKGROUND: Some strains of non-multidrug-resistant, methicillin-resistant
      Staphylococcus aureus (nmMRSA) in Australia are likely to have emerged from
      strains of methicillin-susceptible S. aureus (MSSA) in remote Aboriginal
      communities. OBJECTIVE: To describe the clinical epidemiology of infection due to
      community-associated MRSA strains in an Australian tropical hospital setting with
      a significant Aboriginal population and to compare infections caused by community
      associated strains of MRSA, health-care-associated strains of MRSA, and MSSA
      strains with respect to demographic risk factors and clinical outcomes. Methods.
      We queried the microbiology database for the Top End of the Northern Territory,
      Australia, to determine population incidences for S. aureus infection and
      conducted a prospective matched case-control study to compare infection due to
      nmMRSA, MSSA, or multidrug-resistant MRSA at the Royal Darwin Hospital. RESULTS:
      The annual incidence of S. aureus bacteremia was 65 cases per 100,000 population,
      but in the Aboriginal population the incidence was 172 cases per 100,000
      population (odds ratio [OR] compared with non-Aboriginal population, 5.8 [95%
      confidence interval {CI}, 3.8-8.9). Female sex (adjusted OR [aOR], 1.5 [95% CI,
      1.1-2.0) and remote residence (aOR, 1.8 [95% CI, 1.2-2.5]) were associated with
      the isolation of nmMRSA rather than MSSA, but disease spectrum and outcomes were
      similar. Among those from whom nmMRSA was isolated, Aboriginal patients were
      younger (aOR for each additional year, 0.94 [95% CI, 0.92-0.96]), more likely to
      be female (aOR, 3.8 [95% CI, 1.7-8.5]), and more likely to reside in a remote
      community (aOR, 29 [95% CI, 8.9-94]) than non-Aboriginal patients. The presence
      of Panton-Valentine leukocidin in nmMRSA was associated with double the odds of
      sepsis (aOR, 2.2 [95% CI, 1.1-4.6]). CONCLUSIONS: The association of nmMRSA
      infection with female sex and remote residence supports the hypothesis that
      nmMRSA arose from MSSA strains in remote Aboriginal communities where
      staphylococcal disease is highly prevalent. The similar clinical spectrum and
      outcomes for nmMRSA infection and MSSA infection suggest that virulence is not
      correlated with resistance phenotype.

PMID- 19392624
TI  - Sialic acid: a preventable signal for pneumococcal biofilm formation,
      colonization, and invasion of the host.
AB  - The correlation between carbohydrate availability, pneumococcal biofilm
      formation, nasopharyngeal colonization, and invasion of the host has been
      investigated. Of a series of sugars, only sialic acid (i.e., N-acetylneuraminic
      acid) enhanced pneumococcal biofilm formation in vitro, at concentrations similar
      to those of free sialic acid in human saliva. In a murine model of pneumococcal
      carriage, intranasal inoculation of sialic acid significantly increased
      pneumococcal counts in the nasopharynx and instigated translocation of
      pneumococci to the lungs. Competition of both sialic acid-dependent phenotypes
      was found to be successful when evaluated using the neuraminidase inhibitors DANA
      (i.e., 2,3-didehydro-2-deoxy-N-acetylneuraminic acid), zanamivir, and
      oseltamivir. The association between levels of free sialic acid on mucosae,
      pneumococcal colonization, and development of invasive disease shows how a host
      derived molecule can influence a colonizing microbe and also highlights a
      molecular mechanism that explains the epidemiologic correlation between
      respiratory infections due to neuraminidase-bearing viruses and bacterial
      pneumonia. The data provide a new paradigm for the role of a host compound in
      infectious diseases and point to new treatment strategies.

PMID- 19392625
TI  - Genital human papillomavirus prevalence and human papillomavirus concordance in
      heterosexual couples are positively associated with human immunodeficiency virus
      coinfection.
AB  - This study examined the concordance of genital human papillomavirus (HPV)
      infection in 254 heterosexually active couples and the impact of HIV coinfection.
      Genital HPV detection was significantly more common among HIV-infected women than
      among HIV-seronegative women (99 [68%] of 145 women vs. 33 [31%] of 107 women; P
      < .001); similarly, HPV detection was significantly more common among HIV
      infected men than among HIV-seronegative men (67 [72%] of 93 and 65 [43%] of 150
      men, respectively; P < .001). HIV-seronegative male partners of HIV-infected
      women had a significantly greater prevalence of HPV infection than did HIV
      seronegative male partners of HIV-seronegative women (38 [58%] of 65 men vs. 27
      [32%] of 85 men; P = .001), indicating that HIV coinfection in one partner has a
      significant impact on the prevalence of HPV genital infection in the other
      partner. HPV concordance between couples was associated with HIV infection status
      (P < .001, by Pearson's chi2 test) and was significantly higher among HIV
      infected couples than among HIV-seronegative couples. Type-specific sharing of
      HPV was associated with HIV concordance status (P = .024). HIV-seronegative
      couples were more likely to share 1 HPV type and were unlikely to share >1 type,
      whereas HIV-infected or HIV-discordant couples were more likely to share >1 HPV
      type. Women with a high HPV load frequently shared HPV types with their male
      partners, suggesting that a high HPV load may play a role in HPV transmission
      between partners. In conclusion, HIV coinfection in one or both sexually active
      partners increased HPV prevalence and HPV type-specific concordance.

PMID- 19392623
TI  - The group B streptococcal serine-rich repeat 1 glycoprotein mediates penetration
      of the blood-brain barrier.
AB  - BACKGROUND: Group B Streptococcus (GBS) is the leading cause of bacterial
      meningitis in newborn infants. Because GBS is able to invade, survive, and cross
      the blood-brain barrier, we sought to identify surface-expressed virulence
      factors that contribute to blood-brain barrier penetration and the pathogenesis
      of meningitis. METHODS: Targeted deletion and insertional mutants were generated
      in different GBS clinical isolates. Wild-type and mutant bacteria were analyzed
      for their capacity to adhere to and invade human brain microvascular endothelial
      cells (hBMECs) and to penetrate the blood-brain barrier using our model of
      hematogenous meningitis. RESULTS: Analysis of a GBS (serotype V) clinical isolate
      revealed the presence of a surface-anchored serine-rich protein, previously
      designated serine-rich repeat 1 (Srr-1). GBS Srr-1 is a glycosylated protein with
      high molecular weight. Deletion of srr1 in NCTC 10/84 resulted in a significant
      decrease in adherence to and invasion of hBMECs. Additional mutants in other GBS
      serotypes commonly associated with meningitis showed a similar decrease in hBMEC
      invasion, compared with parental strains. Finally, in mice, wild-type GBS
      penetrated the blood-brain barrier and established meningitis more frequently
      than did the Deltasrr1 mutant strain. CONCLUSIONS: Our data suggest that GBS Srr
      glycoproteins play an important role in crossing the blood-brain barrier and in
      the development of streptococcal meningitis.

PMID- 19392626
TI  - Responses to malarial antigens are altered in helminth-infected children.
AB  - Malaria and helminth infections often coincide in the same tropical regions.
      Studies of the consequences of helminth and malaria coinfection in humans have
      been few and are mainly epidemiological, with little information on cellular
      immune responses. In this study, we investigated the antimalarial immune
      responses of Ghanaian children living in a rural area with a high prevalence of
      both helminth infection and Plasmodium falciparum infection. Whole blood
      specimens were cultured with P. falciparum-infected red blood cells (iRBCs), and
      pro- and anti-inflammatory cytokines and immune regulatory molecules were
      measured. In response to iRBCs, levels of interleukin (IL)-10, but not tumor
      necrosis factor-alpha,were higher in samples from helminth-infected children than
      in those from uninfected children, as was expression of the regulatory molecules
      suppressor of cytokine signaling (SOCS)-3, Foxp3, and programmed death (PD)-1.
      Furthermore, a significant correlation was found between SOCS-3 gene expression
      and IL-10 production. These results indicate that the presence of helminth
      infection modulates the immune response to malarial parasites, making it more
      anti-inflammatory.

PMID- 19392628
TI  - Does HIV-1 subtype D have a higher risk of vertical transmission than other HIV
      subtypes?

PMID- 19392627
TI  - Rosiglitazone modulates the innate immune response to Plasmodium falciparum
      infection and improves outcome in experimental cerebral malaria.
AB  - For severe malarial syndromes such as cerebral malaria, adverse clinical outcomes
      are often mediated by the immune system rather than caused by the parasite
      directly. However, few therapeutic agents have been developed to modulate the
      host's immunopathological responses to infection. Here, we report that the
      peroxisome proliferator-activated receptor gamma (PPARgamma) agonist
      rosiglitazone modulated the host response to malaria by enhancing phagocytic
      clearance of malaria-parasitized erythrocytes and by decreasing inflammatory
      responses to infection via inhibition of Plasmodium falciparum
      glycosylphosphatidylinositol-induced activation of the mitogen-activated protein
      kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) signaling pathways. We found
      that, in the Plasmodium berghei strain ANKA experimental model of cerebral
      malaria, rosiglitazone modified the inflammatory response to malarial infection
      and improved the survival rate even when treatment was initiated as late as day 5
      after infection. Furthermore, rosiglitazone reduced the parasitemia in a CD36
      dependent manner in the Plasmodium chabaudi chabaudi hyperparasitemia model.
      These data suggest that PPARgamma agonists represent a novel class of host
      immunomodulatory drugs that may be useful for treatment of severe malaria
      syndromes.

PMID- 19392630
TI  - The role played by interleukin-10 in cytokine and chemokine dysregulation during
      secondary pneumococcal pneumonia after influenza.

PMID- 19392631
TI  - Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C
      virus (HCV) in European HIV-infected patients with anti-HCV antibodies.

PMID- 19392634
TI  - Accessory gene regulator dysfunction: an advantage for Staphylococcus aureus in
      health-care settings?

PMID- 19392635
TI  - Coinfections with Schistosoma haematobium, Necator americanus, and Entamoeba
      histolytica/Entamoeba dispar in children: chemokine and cytokine responses and
      changes after antiparasite treatment.
AB  - The effect of polyparasite infections on cytokine and chemokine responses as well
      as the effect of antiparasite treatment was studied in children without parasite
      infection (the G0 group), in children singly infected with Schistosoma
      haematobium (the G1 group), and in children multiply infected with S.
      haematobium/Schistosoma mansoni, Entamoeba histolytica/Entamoeba dispar, and
      Necator americanus (the G3+ group). Linear regression analysis disclosed a
      significant risk for coinfection with hookworm and Schistosoma species.
      Polyparasite infections detected in 23% of children before treatment were present
      in 5% at 15 months after treatment. Chemokine responses to S. mansoni adult worm
      antigen (SmAg) diminished after treatment for macrophage inflammatory chemokine
      (MIP)-1alpha/chemokine (C-C motif) ligand (CCL)-3 (among G3+ children, by a
      factor of 200 [95% confidence interval {CI}, 33-1111]) and for MIP-1beta/CCL-4
      (among G3+ children, by a factor of 26 [95% CI, 6-117]) but were enhanced for
      thymus- and activation-regulated chemokine/CCL-17 (among G3+ children, by a
      factor of 10 [95% CI, 3-32]) (P < .001 for all). In response to E. histolytica
      antigen, interleukin (IL)-13 levels increased after treatment among G1 children
      by a factor of 138 (95% CI, 12-1569) and among G3+ children by a factor of 21
      (95% CI, 7-64) (P < .001 for both). Cellular production of interferon (IFN)-gamma
      in response to SmAg decreased 4 weeks after treatment among G3+ children, whereas
      T helper cell type 2 (Th2) IL-13 production was enhanced among G1 and G3+
      children. In summary, polyparasite infections with S. haematobium/S. mansoni, E.
      histolytica/E. dispar, and N. americanus generated prominent proinflammatory
      cytokine and chemokine responses, and, after antihelminth treatment, the
      inflammatory chemokine response lessened as the Th2 responsiveness in coinfected
      children increased.

PMID- 19392636
TI  - Isoniazid plasma concentrations in a cohort of South African children with
      tuberculosis: implications for international pediatric dosing guidelines.
AB  - BACKGROUND: In most countries with a high burden of tuberculosis, children with
      tuberculosis are prescribed isoniazid at dosages of 4-6 mg/kg/day, as recommended
      by international authorities. METHODS: We studied isoniazid concentrations in 56
      hospitalized children (median age, 3.22 years; interquartile range [IQR], 1.58
      5.38 years) who received isoniazid daily (median dosage, 5.01 mg/kg/day; range,
      2.94-15.58 mg/kg/day) as part of antituberculosis treatment. At 1 and 4 months
      after initiation of treatment, isoniazid concentrations were measured in plasma
      samples at 0.75, 1.5, 3, 4, and 6 h after a treatment dose, to describe
      pharmacokinetic measures by using noncompartmental analysis. The effects of dose
      in milogram per kilogram, acetylator genotype, age, sex, and clinical diagnosis
      of kwashiorkor and human immunodeficiency virus (HIV) infection on isoniazid
      concentrations were evaluated. RESULTS: Median peak concentrations of isoniazid
      in children prescribed a dose of 4-6 mg/kg were 58% lower than those in children
      prescribed a dose of 8-10 mg/kg (2.39 mg/L [IQR, 1.59-3.40] vs. 5.71 mg/L [IQR,
      4.74-7.62]). Peak concentrations were <3 mg/L in 70% of children prescribed a
      dose of 4-6 mg/kg. In contrast, children prescribed a dose of 8-12 mg/kg achieved
      peak concentrations approximating those in adults treated with 300 mg of
      isoniazid daily. Intermediate or fast acetylator genotype independently predicted
      a 38% (95% confidence interval [CI], 21%-51%) reduction in peak concentrations,
      compared with the slow-acetylator genotype. Each 1-mg/kg increase in the dose and
      each year increase in age were associated with increases in peak concentrations
      of 21% (95% CI, 16%-25%) and 6% (95% CI, 3%-10%), respectively. CONCLUSIONS:
      Younger children require higher doses of isoniazid per kilogram of body weight to
      achieve isoniazid concentrations similar to those in adults. A daily isoniazid
      dose of 8-12 mg/kg should be recommended.

PMID- 19392637
TI  - Health-related quality of life and posttraumatic stress disorder among survivors
      of left-sided native valve endocarditis.
AB  - BACKGROUND: The long-term prognosis of endocarditis is described primarily in
      relation to clinical outcome measures-for example, such complications as
      cerebrovascular accident, cardiac failure, need for cardiac surgery, relapse
      rate, and mortality. To our knowledge, to date, no studies have examined the
      health-related quality of life and the prevalence of long-term persistence of
      physical symptoms for survivors of left-sided native valve endocarditis. METHODS:
      We conducted a prospective follow-up study of patients treated for left-sided
      native valve endocarditis from 1 November 2000 through 31 October 2003 in 23
      hospitals in the Netherlands. Of 86 patients eligible to participate, 55
      completed questionnaires administered 3 m and 12 m after discharge; an additional
      12 patients completed questionnaires 12 m after discharge only, making a total of
      67 patients in our study. Persistence of symptoms and employment status were
      recorded. The health-related quality of life was measured by using the Dutch
      version of the Medical Outcomes Study Short Form 36-item health survey and the
      Posttraumatic Stress Disorder questionnaire. RESULTS: Three months after the end
      of antimicrobial treatment, 41 (75%) of 55 patients still had physical symptoms.
      Twelve months after the end of antimicrobial treatment, 36 (54%) of 67 patients
      still had physical symptoms. Before the episode of endocarditis, 30 (81%) of 37
      patients aged < or =60 years were employed and working. At 3 m follow-up, 16
      (52%) of 31 patients returned to work, and at 12 m follow-up, 24 (65%) of 37
      patients were working. One year after discharge, the health-related quality of
      life was impaired in 5 of 8 dimensions, compared with age-adjusted standard
      values, and 7 (11%) of 64 patients suffered from posttraumatic stress disorder.
      CONCLUSIONS: A year after discharge, most survivors of left-sided native valve
      endocarditis still had persisting symptoms and a seriously diminished quality of
      life, and 11% of patients suffered from posttraumatic stress disorder.

PMID- 19392638
TI  - Current and future therapies for age-related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration is the leading cause of blindness,
      with an increasing incidence as the elderly population expands. OBJECTIVE: In
      this article we review current therapeutic strategies and discuss possible future
      targets. METHODS: A review of the literature and ongoing clinical trials was
      undertaken. RESULTS: Currently, established therapies for neovascular AMD-like
      photodynamic therapy and anti-VEGF therapies allow stabilization or even
      improvement of vision. Potential future drugs under development for advanced AMD
      or its prevention target the signal transduction cascade of different angiogenic
      molecules. These drugs intervene at different levels of the involved processes
      including the RNA production and specific protein expression as well as
      inflammatory, apoptotic, or metabolic processes. CONCLUSION: Combining different
      strategies targeting angiogenesis, inflammation and apoptosis, or interfering
      early in--or even prior to--the formation of choroidal neovascularization, may
      improve the future management of age-related macular degeneration.

PMID- 19392639
TI  - Toward optimal health: current approaches to standards of care for diabetes in
      women. Interview by Jodi R. Godfrey.

PMID- 19392640
TI  - Women veterans and outcomes after acute myocardial infarction.
AB  - BACKGROUND: Previous studies have shown that women have decreased survival and
      receive fewer cardiac procedures after acute myocardial infarction (AMI) compared
      with men, raising concerns for sexual bias in provision of care. The objective of
      this study is to describe clinical characteristics, treatment, and survival in
      women veterans compared with men after admission to VA hospitals for AMI.
      METHODS: This is a retrospective inception cohort study using data drawn from the
      VA Cardiac Care Follow-up Clinical Study, describing patients admitted for AMI to
      VA hospitals from October 1, 2003 to March 31, 2005. Subjects were followed for 1
      year. RESULTS: There were 236 women and 13,259 men admitted during the study
      period to VA hospitals with AMI. Women were less likely to have a history of
      heart failure compared with men (18.2% of women vs. 27.2% of men, p = 0.002) and
      previous coronary artery bypass grafting (CABG) (11.4% of women vs. 19.6% of men,
      p = 0.002). Diagnostic cardiac catheterization was similar in women and men
      (36.9% and 34.9%, p = 0.539). Crude in-hospital mortality was 4.2% for women and
      7.6% for men (p = 0.051). After adjusting for comorbidities and treatment
      variables, in-hospital mortality was not significantly different for women
      compared with men (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.60
      1.12). CONCLUSIONS: Women veterans receive a level of care similar to men
      veterans for MI treated in VA hospitals. Differences in mortality between women
      and men were not significant and do not suggest that women fare worse.

PMID- 19392641
TI  - Comparative study of the changes in partial pressure of plasma carbon dioxide
      during carbon dioxide insufflation into the intraperitoneal and preperitoneal
      spaces.
AB  - BACKGROUND: We aimed to compare plasma concentrations of carbon dioxide (CO(2))
      in dogs that underwent intra- and preperitoneal CO(2) insufflation. MATERIALS AND
      METHODS: Thirty dogs were studied. Ten formed a control group, 10 underwent
      intraperitoneal CO(2) insufflation, and 10 underwent preperitoneal CO(2)
      insufflation. General anesthesia with controlled ventilation was standardized for
      all dogs. After stabilizing the anesthesia, blood samples were collected at
      predetermined times and were sent for immediate gasometric analysis. Analysis of
      variance was used for comparing variables. RESULTS: The plasma CO(2)
      concentration in the intraperitoneal insufflation group increased significantly
      more than in the preperitoneal insufflation group and was significantly greater
      than in the control group (P < 0.05). The pH values in the intraperitoneal group
      were lower than in the preperitoneal group (P < 0.05). CONCLUSION: The data from
      this study suggest that a greater plasma concentration of CO(2) is achieved by
      insufflation at constant pressure into the intraperitoneal space than into the
      preperitoneal space.

PMID- 19392642
TI  - A review on techniques for tremor recording and quantification.
AB  - Tremor is the most common movement disorder and differs from other disorders by
      its repetitive, stereotyped movements, with regular frequency and amplitude. The
      three most frequent pathological forms of it are the essential tremor (ET), the
      Parkinson's disease (PD) tremor, and the enhanced physiological tremor. The ET
      and PD tremor affect the older population mostly. Although there are cases of
      tremor reported since ancient times, there is currently no consensus about its
      causes or about its main differential characteristics. In this article, we
      present a review of the methods more frequently used in measurement and analysis
      of tremor and the difficulties encountered in the research for the identification
      of methodologies that allow a significant advance in the study of tremor.

PMID- 19392643
TI  - Collagens of articular cartilage: structure, function, and importance in tissue
      engineering.
AB  - Collagen is a crucial matrix component of articular cartilage. Because articular
      cartilage is a load bearing tissue, developing mechanical integrity is a central
      goal of tissue engineering. The significant role of collagen in cartilage
      biomechanics necessitates creating a collagen network in tissue engineered
      constructs. An extensive network of collagen fibrils provides cartilage with
      mechanical integrity, but developing strategies to replicate this collagen
      network remains a challenge for articular cartilage tissue engineering efforts.
      To study the structure and biomechanics of the collagen network, many
      experimental and computational methodologies have been developed. However,
      despite extensive cartilage tissue engineering research, few studies have
      assessed collagen type, crosslinks, or fibril orientation. Further study of the
      collagen network, both within native tissue and engineered neotissue, will enable
      more robust constructs to be developed. This review focuses on the biology and
      biomechanics of the collagen network, relevant experimental methods for assessing
      the collagen network, and articular cartilage tissue engineering studies that
      have examined collagen.

PMID- 19392644
TI  - Alternative devices for the quantification of human motion.
AB  - Force platforms and video tracking systems have been used to characterize subject
      movements and resultant forces to identify common characteristics of individuals
      who have experienced recurring falls. Short-term training using force platforms
      with feedback has been effective in reducing sway. Because of the expense and
      size requirements of these systems, researchers have pursued alternate means of
      quantifying postural motion. Most recently, this has involved various
      combinations of accelerometers and gyroscopes. This review article summarizes the
      main aspects of many of these designs and shows the high correlation of results
      obtained relative to video tracking methods. Most notably, measurements of the
      lower leg have reached correlation coefficients as high as 0.98 when using high
      pass filters to eliminate signal drift. Many complications have been overcome,
      such that accelerometers and gyroscopes are considered acceptable for use in
      human motion measurement devices.

PMID- 19392646
TI  - Expression of members of the dystrophin, dystrobrevin, and dystrotelin
      superfamily.
AB  - The dystrophin/dystrobrevin/dystrotelin superfamily is marked by a common
      constellation of domains whose juxtaposition is tightly constrained in all three
      subfamilies. These domains comprise a cluster of four closely packed EF hands, a
      ZZ domain, and two coiled-coil regions. In addition, the dystrophin and
      dystrobrevin branches share one or two binding sites for members of the
      syntrophin family of adaptor proteins, and the dystrophins and some dystrotelins
      share a WW domain. Much of the exon structure of the genes encoding these domains
      is also shared, confirming the monophyletic status of the superfamily. Almost all
      animals have at least one member of each branch, with multiple paralogous members
      of the dystrophin and dystrobrevin branches in the vertebrates. Thus, in humans,
      6 genes, 19 promoters, and 10 alternatively spliced exons conspire to generate a
      staggering array of proteins, with at least one in almost every tissue of the
      body. This review aims to summarize what is known of this complexity of
      expression of members of the dystrophin/dystrobrevin/dystrotelin superfamily
      across the animal kingdom. The widespread expression in adult vertebrates,
      together with elaborate and dynamic patterns during development, paints a picture
      of a superfamily whose fundamental biological function is still poorly
      understood.

PMID- 19392649
TI  - Coordinated regulation of Ras-, Rac-, and Ca2+-dependent signaling pathways.
AB  - Stimulation of cells by a broad variety of agonists results in a coordinated
      activation of Ca2+-, Ras-, and Rac-dependent pathways, which have to synergize to
      yield the corresponding biological response. This synergy requires a dense net of
      mutually positive and negative regulatory mechanisms. These include Ca2+-mediated
      activation of guanine nucleotide exchange proteins, resulting in increased levels
      of GTP-charged Ras and/or Rac or inactivation of small GTPases by Ca2+-mediated
      activation of GTPase-activating enzymes. Likewise, Ras as well as Rac control
      regulatory mechanisms, resulting in increased or diminished levels of cytosolic
      free Ca2+. The biochemical mechanisms underlying these effects are discussed,
      with special reference to regulation of Ca2+ signaling by Ras and Rac.

PMID- 19392647
TI  - Marrow fat and the bone microenvironment: developmental, functional, and
      pathological implications.
AB  - Bone marrow adipogenesis is a normal physiologic process in all mammals. However,
      its function is unknown. The mesenchymal stem cell is the marrow precursor for
      adipocytes as well as osteoblasts, and PPARG is an essential differentiation
      factor for entrance into the fat lineage. Mouse models have provided significant
      insight into the molecular cues that define stromal cell fate. In humans,
      accelerated marrow adipogenesis has been associated with aging and several
      chronic conditions, including diabetes mellitus and osteoporosis. Newer imaging
      techniques have been used to determine the developmental time course of fat
      generation in bone marrow. However, more studies are needed to understand the
      interrelationship among hematopoietic, osteoblastic, and adipogenic cells within
      the marrow niche.

PMID- 19392650
TI  - Modern concepts in the diagnosis and treatment of vitamin D deficiency and its
      clinical consequences.
AB  - It is the purpose of this comprehensive report to outline a revolutionary
      strategy to prevent vitamin D deficiency in our nation. Vitamin D is a unique
      vitamin. Its metabolic product, calcitriol, is a profound secosteroid hormone
      that has impact on over 1000 genes in the human body. Recent clinical research
      has implicated vitamin D deficiency as a major factor in the etiology of rickets,
      a wide variety of cancers, as well as hypertension, stroke, heart attack,
      diabetes, bone fractures, periodontal disease, and even multiple sclerosis. There
      are two forms of vitamin D utilized in the human body: D2 and D3. Measurement of
      25(OH)D is the most reliable method of detecting vitamin D deficiency. Several
      methods, including high-performance liquid chromatography (HPLC),
      chemoluminescence, and radioimmunoassay (RIA), have been developed for the
      measurement of total 25(OH)D levels. Prevention and treatment of vitamin D
      deficiency is accomplished by regulated sun exposure as well as vitamin D,
      supplementation. This information describing our plan to prevent vitamin D
      deficiency in the patients and employees of Legacy Health System is a landmark
      accomplishment that should be replicated in every healthcare setting in our
      country to prevent vitamin D deficiency.

PMID- 19392648
TI  - Genetic complexity of the human innate host defense molecules, surfactant protein
      A1 (SP-A1) and SP-A2--impact on function.
AB  - Innate immunity mechanisms play a critical role in the primary response to
      invading pathogenic microorganisms and other insulting agents. The innate lung
      immune system includes lung surfactant, a lipoprotein complex that carries out a
      function essential for life, that is, reduction of the surface tension at the air
      liquid interphase of the alveolar space. By means of this function, pulmonary
      surfactant prevents lung collapse, therefore ensuring normal lung function and
      lung health. Pulmonary surfactant contains a number of host-defense molecules
      that are involved in the elimination of pathogens, viruses, particles, allergens,
      and other insults, as well as in the control of inflammation. This review is
      concerned with one of the surfactant proteins, the human (h) surfactant protein A
      (hSP-A), which, in addition to its role in surfactant-related functions, plays an
      important role in the modulation of lung host defense. The hSP-A locus has been
      identified with extensive complexity that may have an impact on its function,
      structure, and regulation. In humans, two genes--SP-A1 (SFTPA1) and SP-A2
      (SFTPA2)--encode SP-A, with SP-A2 gene products being more biologically active
      than SP-A1 in most of the in vitro assays investigated. Although the two hSP-A
      genes share a high level of sequence similarity, differences in the structure and
      function between SP-A1 and SP-A2 have been observed in recent studies. In this
      review, we discuss the human SP-A complexity and how this may affect SP-A
      function.

PMID- 19392651
TI  - Accelerated proteasomal activity induced by Pb2+, Ga3+, or Cu2+ exposure does not
      induce degradation of alpha-synuclein.
AB  - The involvement of environmental heavy metals in Parkinson's disease (PD) has
      been suggested by epidemiologic studies; however, the mechanism of this effect is
      unknown. PD is characterized by the aggregation of alpha-synuclein in Lewy
      bodies. We previously showed that Pb2+ accelerates proteasomal activity.
      Therefore, we examined the effect of Pb2+, Ga3+, and Cu2+ on alpha-synuclein in
      human SH-SY5Y cells. The heavy metals induced an increase in heme-oxygenase-1
      levels without significant cell death or ROS generation. The metals inhibited ALA
      dehydratase, which is the inhibitory subunit of the proteasome, thereby
      accelerating proteasomal activity and decreasing protein levels of CDK-1 and
      PBGD. However, alpha-synuclein protein levels increased after exposure to metals,
      similar to the effect obtained with the proteasome inhibitor, hemin, suggesting
      that alpha-synuclein is inaccessible to proteasomal degradation. Indeed, electron
      microscopy revealed the formation of aggresomes in Pb2+- or hemin-treated cells.
      Thus, although heavy metals enhance proteasomal activity, alpha-synuclein is
      protected from degradation, and its protein levels and aggregation are increased.

PMID- 19392653
TI  - The cyclooxygenase-2 inhibitor etoricoxib is a potent chemopreventive agent of
      colon carcinogenesis in the rat model.
AB  - Cyclooxygenase-2 (COX-2), an inducible prostaglandin G/H synthase, is
      overexpressed in several human cancers, including colon cancer, and therefore the
      potential ability of a selective COX-2 inhibitor, etoricoxib, is considered in
      the prevention of the 1,2-dimethyl hydrazine (DMH)-induced colon carcinogenesis
      in the rat model. DMH was injected s.c. for 6 weeks, whereas etoricoxib was fed
      orally to the rats on a daily basis. The results showed that DMH produced a very
      high number of multiple plaque lesions (MPLs), putative neoplastic biomarkers,
      localized throughout the colon, whereas considerable regression was observed with
      etoricoxib treatment. In addition, the etoricoxib group was the only group that
      exhibited very few of these lesions. Histopathological analysis revealed extreme
      dysplasia, a few adenomas, and other carcinogenic changes in the DMH group, which
      are distinctly absent in the etoricoxib-treated group. COX-2 was also seen to be
      highly expressed following DMH treatment. The DMH treatment caused very few
      apoptotic cells, as determined by the TUNEL assay of the colonic mucosa in
      paraffin sections whose number greatly increased following etoricoxib treatment.
      Because all these changes were clearly reversed by etoricoxib in DMH-treated
      animals, and the use of etoricoxib alone did not produce a neoplastic effect per
      se, it appears that etoricoxib, a selective COX-2 inhibitor, might be a safe and
      potentially chemopreventive agent in colon cancer.

PMID- 19392652
TI  - Siva-1 promotes K-48 polyubiquitination of TRAF2 and inhibits TCR-mediated
      activation of NF-kappaB.
AB  - The proapoptotic protein Siva-1 plays an important role in some of the extrinsic
      and intrinsic apoptosis signaling pathways in cancer cells. Previously, we showed
      that Siva-1 inhibited the activity of the prosurvival transcription factor NF
      kappaB. In the present study, upon TCR cross-linking of Jurkat T leukemia cells,
      we demonstrated that the inhibitory target of Siva-1 is upstream of the IKK
      complex in the NF-kappaB signaling pathway. Additionally, Siva-1 also suppressed
      the activity of another crucial transcription factor AP-1, and a common mediator
      of both these pathways is the adaptor protein TRAF2. Further, we observed that
      Siva-1 indeed interacted with TRAF2 and negatively regulated its activity by
      promoting K48-hnked polyubiquitination. Siva-1 specifically interacted with the
      ring finger domain of TRAF2, which is essential for its E3 hgase activity and its
      ability to subsequently activate NF-kappaB. TCR cross-linking of Jurkat T cells
      that lacked Siva-1 revealed significantly lowered K48- but elevated K63
      ubiquitinated TRAF2 levels upon TCR cross-linking, suggesting that the
      differential pattern of ubiquitination in these cells essentially contributed to
      a robust and sustained activation of NF-kappaB. The above results demonstrated an
      important role for endogenous Siva-1 in negatively regulating NF-kappaB
      activation by targeting TRAF2.

PMID- 19392654
TI  - Revolutionary advances in the diagnosis and treatment of Familial Adenomatous
      Polyposis.
AB  - During the last 25 years, there have been revolutionary advances in the treatment
      of Familial Adenomatous Polyposis (FAP). The purpose of this article is to
      describe the pathophysiology, genetic testing, surveillance, surgical
      interventions, and psychosocial issues. The genetic defect in FAP is germline
      mutation in the adenomatous polyposis coli (APC) gene. Syndromes once thought to
      be distinct from FAP are now recognized to be part of the phenotypic spectrum of
      FAP. Syndromes with a germline mutation in the APC gene include FAP, Gardner
      syndrome, Turcot syndrome, and Attenuated Adenomatous Polyposis Coli (AAPC). FAP
      is a germline mutation in the APC gene with onset of florid polyposis in
      childhood and development of colorectal cancer by age 30. Colectomy is advised
      because of the high risk of developing colorectal cancer. AAPC is a variant of
      this condition with later age of onset and milder clinical phenotype. However,
      colectomy is advised once polyposis develops and polyps cannot be managed
      endoscopically. Despite the unique advances in genetic testing, psychosocial
      management of these syndromes remains to be a challenging problem.

PMID- 19392655
TI  - Radioprotective effects of Aloe vera leaf extract on Swiss albino mice against
      whole-body gamma irradiation.
AB  - The skin, being a cell-renewal system, is one of the first organs to be affected
      in total-body irradiation during radiotherapy. An attempt has been made in the
      present study to explore radiation-induced biochemical alterations caused by
      whole-body gamma irradiation and their modulation in Swiss albino mice by Aloe
      vera leaf extract (AVE). Mice were selected for this study from an inbreed colony
      and divided into four different groups: I (double-distilled water-treated group):
      considered as normal; II (Aloe vera-treated group): the animals were administered
      1 g/kg body-wt/day Aloe vera leaf extract; III (radiation-treated group): the
      animals were exposed to 6 Gy gamma radiation at the dose rate of 0.96 Gy/min; and
      IV (combination group): animals were administered Aloe vera leaf extract
      continuously for 15 consecutive days, and on the 15th day they were irradiated to
      6 Gy gamma radiation after 30 minutes of extract administration. The animals from
      the above groups were autopsied after 6 hours, 24 hours, and at 3, 7, 14, and 21
      days of radiation. Biochemical estimations of DNA, lipid peroxidation,
      glutathione, catalase, and superoxide-dismutase were made. Total DNA, catalase,
      superoxide dismutase (SOD) activity in the skin, and glutathione (GSH) in the
      liver and blood significantly decreased compared to normal, but lipid
      peroxidation (LPO) in the liver and blood increased in the irradiated control
      group. In contrast, in experimental animals, DNA, catalase, and SOD in the skin
      and GSH in the liver and blood increased significantly, whereas LPO in the liver
      and blood decreased in comparison to irradiated control animals. Thus, Aloe vera
      leaf extract is found to have damage-resistant properties against radiation
      induced biochemical alterations in Swiss albino mice.

PMID- 19392656
TI  - Correlation of FBX dosimeter and micronucleus assay in radiation dosimetry of
      gamma chambers.
AB  - The aim of the present study is to determine the dose distribution in gamma
      irradiation chambers by chemical dosimetry and to establish its correlation with
      biological dosimetry. The dose-distribution studies of these two gamma chambers
      show that compared to the center point of the chambers, the dose rate was 17%-22%
      higher at the circumference. Moreover, the dose rate was 12%-18% lower at the
      bottom and top positions compared to the center point. It was interesting to
      observe that the dose rate determined by chemical dosimetry was well correlated
      with the number of micro-nucleus (MN) formations at different positions of the
      chamber. Our results suggest that the formation of the single MN/cell was better
      correlated with the dose rate than the double MN/cell, suggesting that the number
      of single MN/cells could be better biomarkers for determining the dose rate.
      These results provide a correlation between chemical and biological dosimetry,
      which may have relevance in the development of better bioassay techniques for
      radiation exposure.

PMID- 19392657
TI  - Chromosomal aberrations in subjects exposed to ionizing radiation.
AB  - Occupational exposure to low doses of ionizing radiation is a particularly
      delicate subject for investigation, due to the cumulative effects of chronic
      exposure. It is extremely important to consider and to measure the biological
      response to given conditions of exposure. The aim of this study was to establish
      possible recovery from DNA damage in subjects professionally exposed to radiation
      in their working area by examinations for chromosomal aberrations (CA) at two
      different times. The first group (I) was composed of 30 professionally exposed
      subjects in whom unstable CA (dicentrics, ring, acentric fragments, chromatid,
      chromosomal breaks, and chromatid interchanges) were identified at time zero.
      After removal from the radiation area, they were re-examined 9 months later. The
      second group (II) contained 64 healthy individuals, not professionally exposed to
      ionizing radiation or other known mutagenic agents. In the group of exposed
      individuals, five (16.67%) subjects exhibited permanent unstable CAs, even after
      9 months absence from the radiation. When the nonexposed and exposed groups were
      compared, an increase of unstable aberrations (p < 0.05) was observed in the
      exposed group. Nevertheless, a statistically significant decrease of dicentrics,
      acentric fragments, and ring frequencies was observed in exposed individuals
      after 9 months away from the radiation area. However, chromatid and isochromatid
      break frequencies increased slightly but not significantly after 9 months. The
      detected CAs corresponded to the total effective doses of radiation measured in
      our subjects. The existence of CAs in some individuals even after absence from
      the radiation area suggests that the time necessary for the damaged DNA to
      recover is extremely variable and indicates interindividual differences in
      radiosensitivity as well as differences in the cellular-reparation response.

PMID- 19392658
TI  - A paradox of cadmium: a carcinogen that impairs the capability of human breast
      cancer cells to induce angiogenesis.
AB  - Cadmium, a highly persistent heavy metal, has been categorized as a human
      carcinogen. Even though it is known that cadmium acts as estrogens in breast
      cancer cells, several studies failed to demonstrate whether cadmium is a causal
      factor for breast cancer. The lack of a strong association between cadmium and
      breast cancer could be found in the antiangiogenic properties of this heavy
      metal, which might counteract its carcinogenic properties in the progression of
      breast cancer. In this study, we exposed estrogen-responsive breast cancer cells
      to subtoxic levels of cadmium, and we evaluated their angiogenic potential using
      the chick embryo chorioallantoic membrane assay. Exposure of breast cancer cells
      to subtoxic levels of cadmium significantly inhibited the angiogenic potential of
      the breast cancer cell line, suggesting the possibility that cadmium might
      negatively regulate the production of proangiogenic factors in breast cancer
      cells. Our results suggest that cadmium might exert a paradoxical effect in
      breast cancer: on the one hand, it could promote carcinogenesis, and, on the
      other hand, it could delay the onset of tumors by inhibiting breast cancer cell
      induced angiogenesis.

PMID- 19392659
TI  - Characterization of SENP7, a SUMO-2/3-specific isopeptidase.
AB  - The modification of proteins by SUMO (small ubiquitin-related modifier) plays
      important roles in regulating the activity, stability and cellular localization
      of target proteins. Similar to ubiquitination, SUMO modification is a dynamic
      process that can be reversed by SENPs [SUMO-1/sentrin/SMT3 (suppressor of mif two
      3 homologue 1)-specific peptidases]. To date, six SENPs have been discovered in
      humans, although knowledge of their regulation, specificity and biological
      functions is limited. In the present study, we report that SENP7 has a restricted
      substrate specificity, being unable to process SUMO precursors and displaying
      paralogue-specific isopeptidase activity. The C-terminal catalytic domain of
      SENP7 efficiently depolymerized poly-SUMO-2 chains but had undetectable activity
      against poly-SUMO-1 chains. SENP7 also displayed isopeptidase activity against di
      SUMO-2- and SUMO-2-modified RanGAP1 (Ran GTPase-activating protein 1) but had
      limited activity against SUMO-1-modified RanGAP1. in vivo, full-length SENP7 was
      localized to the nucleoplasm and preferentially reduced the accumulation of high
      molecular-mass conjugates of SUMO-2 and SUMO-3 compared with SUMO-1. Small
      interfering RNA-mediated ablation of SENP7 expression led to the accumulation of
      high-molecular-mass SUMO-2 species and to the accumulation of promyelocytic
      leukaemia protein in subnuclear bodies. These findings suggest that SENP7 acts as
      a SUMO-2/3-specific protease that is likely to regulate the metabolism of poly
      SUMO-2/3 rather than SUMO-1 conjugation in vivo.

PMID- 19392660
TI  - Functional characterization of LePGT1, a membrane-bound prenyltransferase
      involved in the geranylation of p-hydroxybenzoic acid.
AB  - The AS-PT (aromatic substrate prenyltransferase) family plays a critical role in
      the biosynthesis of important quinone compounds such as ubiquinone and
      plastoquinone, although biochemical characterizations of AS-PTs have rarely been
      carried out because most members are membrane-bound enzymes with multiple
      transmembrane alpha-helices. PPTs [PHB (p-hydroxybenzoic acid)
      prenyltransferases] are a large subfamily of AS-PTs involved in ubiquinone and
      naphthoquinone biosynthesis. LePGT1 [Lithospermum erythrorhizon PHB
      geranyltransferase] is the regulatory enzyme for the biosynthesis of shikonin, a
      naphthoquinone pigment, and was utilized in the present study as a representative
      of membrane-type AS-PTs to clarify the function of this enzyme family at the
      molecular level. Site-directed mutagenesis of LePGT1 with a yeast expression
      system indicated three out of six conserved aspartate residues to be critical to
      the enzymatic activity. A detailed kinetic analysis of mutant enzymes revealed
      the amino acid residues responsible for substrate binding were also identified.
      Contrary to ubiquinone biosynthetic PPTs, such as UBIA in Escherichia coli which
      accepts many prenyl substrates of different chain lengths, LePGT1 can utilize
      only geranyl diphosphate as its prenyl substrate. Thus the substrate specificity
      was analysed using chimeric enzymes derived from LePGT1 and UBIA. In vitro and in
      vivo analyses of the chimeras suggested that the determinant region for this
      specificity was within 130 amino acids of the N-terminal. A 3D (three
      dimensional) molecular model of the substrate-binding site consistent with these
      biochemical findings was generated.

PMID- 19392661
TI  - Distribution, pharmacological characterization and function of the 18 kDa
      translocator protein in rat small intestine.
AB  - BACKGROUND INFORMATION: The TSPO (18 kDa translocator protein) is a mitochondrial
      transmembrane protein involved in cholesterol transport in organs that synthesize
      steroids and bile salts. Different natural and synthetic high-affinity TSPO
      ligands have been characterized through their ability to stimulate cholesterol
      transport, but also to stimulate other physiological functions including cell
      proliferation, apoptosis and calcium-dependent transepithelial ion secretion.
      Here, we investigate the localization and functions of TSPO in the small
      intestine. RESULTS: TSPO was present in enterocyte mitochondria but not in rat
      intestinal goblet cells. Enterocyte cytoplasm also contained the endogenous TSPO
      ligand, polypeptide DBI (diazepam-binding inhibitor). Whereas intestinal TSPO had
      high affinity for the synthetic ligand PK 11195, the pharmacological profile of
      TSPO in the duodenum was distinct from the jejunum and ileum. Specifically,
      benzodiazepine Ro5-4864 and protoporphyrin IX showed 5-13-fold lower affinity for
      duodenal TSPO. The mRNA and protein ratios of TSPO to other mitochondrial
      membrane proteins VDAC (voltage-dependent anion channel) and ANT (adenine
      nucleotide transporter) were significantly different. PK 11195 stimulated calcium
      dependent chloride secretion in the duodenum and calcium-dependent chloride
      absorption in the ileum, but did not affect jejunum ion transport. CONCLUSIONS:
      The functional differences in subpopulations of TSPO in different regions of the
      intestine could be related to structural organization of mitochondrial protein
      complexes that mediate the ability of TSPO to modulate either chloride secretion
      or absorption in the duodenum and ileum respectively.

PMID- 19392662
TI  - NAD(P)H oxidase-mediated reactive oxygen species production alters astrocyte
      membrane molecular order via phospholipase A2.
AB  - ROS (reactive oxygen species) overproduction is an important underlying factor
      for the activation of astrocytes in various neuropathological conditions. In the
      present study, we examined ROS production in astrocytes and downstream effects
      leading to changes in the signalling cascade, morphology and membrane dynamics
      using menadione, a redox-active compound capable of inducing intracellular ROS.
      NAD(P)H oxidase-mediated menadione-induced ROS production, which then stimulated
      phosphorylation of p38 MAPK (mitogen-activated protein kinase) and ERK1/2
      (extracellular-signal-regulated kinase 1/2), and increased actin polymerization
      and cytoskeletal protrusions. We also showed that astrocyte plasma membranes
      became more molecularly ordered under oxidative stress, which was abrogated by
      down-regulating cPLA2 (cytosolic phospholipase A2) either with a pharmacological
      inhibitor or by RNA interference. In addition, mild disruption of F-actin with
      cytochalasin D suppressed menadione-enhanced phosphorylation of cPLA2 and
      membrane alterations. Taken together, these results suggest an important role for
      ROS derived from NAD(P)H oxidase in activation of astrocytes to elicit
      biochemical, morphological and biophysical changes reminiscent of reactive
      astrocytes in pathological conditions.

PMID- 19392663
TI  - Rab7: roles in membrane trafficking and disease.
AB  - The endocytosis pathway controls multiple cellular and physiological events. The
      lysosome is the destination of newly synthesized lysosomal hydrolytic enzymes.
      Internalized molecules or particles are delivered to the lysosome for degradation
      through sequential transport along the endocytic pathway. The endocytic pathway
      is also emerging as a signalling platform, in addition to the well-known role of
      the plasma membrane for signalling. Rab7 is a late endosome-/lysosome-associated
      small GTPase, perhaps the only lysosomal Rab protein identified to date. Rab7
      plays critical roles in the endocytic processes. Through interaction with its
      partners (including upstream regulators and downstream effectors), Rab7
      participates in multiple regulation mechanisms in endosomal sorting, biogenesis
      of lysosome [or LRO (lysosome-related organelle)] and phagocytosis. These
      processes are closely related to substrates degradation, antigen presentation,
      cell signalling, cell survival and microbial pathogen infection. Consistently,
      mutations or dysfunctions of Rab7 result in traffic disorders, which cause
      various diseases, such as neuropathy, cancer and lipid metabolism disease. Rab7
      also plays important roles in microbial pathogen infection and survival, as well
      as in participating in the life cycle of viruses. Here, we give a brief review on
      the central role of Rab7 in endosomal traffic and summarize the studies focusing
      on the participation of Rab7 in disease pathogenesis. The underlying mechanism
      governed by Rab7 and its partners will also be discussed.

PMID- 19392664
TI  - Effect of eCG superstimulation and buserelin on cumulus-oocyte complexes recovery
      and maturation in llamas (Lama glama).
AB  - The aim of the present study was two-fold. Experiment I: evaluate the effect of
      buserelin on llama's oocyte maturation after exogenous follicular activity
      suppression, followed by ovarian superstimulation with different doses of equine
      chorionic gonadotropin (eCG). Experiment II: compare the number of follicles
      aspirated and the number of cumulus-oocyte complexes (COCs) recovered according
      to different doses of eCG followed by buserelin. Experiment I consisted in a
      control group (without buserelin) and a treatment group (with buserelin), both
      subdivided according to eCG dose administered: A: 500 IU; B: 1000 IU; C: 1500 IU.
      The treatment group received a single i.v. dose of 8 microg of buserelin when two
      or more dominant follicles were found at ultrasound evaluation and 20 h later
      were subjected to surgery. In group A, 83% of the llamas did not respond to
      superstimulation. In groups B and C differences were observed between the control
      and the treatment groups for the degree of COCs maturation (p < 0.05). In
      experiment II animals were divided into two groups according to the eCG dose
      administered: 1000 and 1500 IU. Twenty hours before surgery females received a
      single i.v. dose of 8 microg of buserelin. Average number of follicles aspirated
      and COCs recovered was higher (p < 0.05) with the administration of 1500 IU of
      eCG. A larger number of expanded COCs were obtained from follicles > or =7 mm in
      diameter. We conclude that buserelin aids the recovery of a larger number of
      expanded COCs. Administration of 1500 IU of eCG produces a higher number of
      follicles for aspiration and number of COCs recovered.

PMID- 19392665
TI  - Expression of apoptosis regulatory genes and incidence of apoptosis in different
      morphological quality groups of in vitro-produced bovine pre-implantation
      embryos.
AB  - Apoptosis occurs during early development in both in vivo- and in vitro-produced
      embryos, and is considered as one of the causes of embryonic loss. The objectives
      of this study were, therefore, investigating stage-specific expression profiles
      of apoptosis regulatory genes in three quality groups of in vitro-produced bovine
      pre-implantation embryos; and analysing the relationship between cell number and
      DNA fragmentation with expressions of those genes. The relative abundance of mRNA
      of 9 pro- (Bax, caspase-9, Bcl-xs, P53, Caspase-3 and Fas) and anti- (Bcl-w and
      Mcl-1) apoptotic genes was analysed. Differential cell staining and terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling were
      performed to analyse the variation in cell numbers and detect apoptotic nuclei
      respectively. Expression of Bax and Caspase-3 genes was significantly (p < 0.05)
      higher in poor quality pre-implantation embryos as compared with that of
      morphologically good quality embryos of the same developmental stages. Moreover,
      Mcl-1 expression was significantly higher in good quality immature oocytes than
      that in the poor quality group. Moreover, higher DNA fragmentation was evidenced
      in morphologically poor quality blastocysts. In conclusion, our study
      demonstrates that Bax, caspase-3 and Mcl-1 can be used as potential markers of
      embryo quality to evaluate in vitro-produced bovine embryos. Further studies are
      required to investigate specific molecular signatures that can be used in
      evaluating in vivo-derived embryos.

PMID- 19392666
TI  - 13,14-Dihydro-15-keto prostaglandin F2alpha release in response to oxytocin
      challenge early post-partum in anoestrous Nelore cows submitted to temporary calf
      removal and progesterone priming.
AB  - The study evaluated, in early post-partum anoestrous Nelore cows, if the increase
      in plasma oestradiol (E2) concentrations in the pre-ovulatory period and/or
      progesterone priming (P4 priming) preceding ovulation, induced by hormonal
      treatment, reduces the endogenous release of prostaglandin PGF(2)alpha and
      prevents premature lysis of the corpus luteum (CL). Nelore cows were subjected to
      temporary calf removal for 48 h and divided into two groups: GPE/eCG group (n =
      10) and GPG/eCG group (n = 10). Animals of the GPE/eCG group were treated with a
      GnRH agonist. Seven days later, they received 400 IU of eCG, immediately after
      PGF(2)alpha treatment, and on day 0, 1.0 mg of oestradiol benzoate (EB). Cows of
      the GPG/eCG group were similarly treated as those of the GPE/eCG group, except
      that EB was replaced with a second dose of GnRH. All animals were challenged with
      oxytocin (OT) 9, 12, 15 and 18 days after EB or GnRH administration and blood
      samples were collected before and 30 min after OT. Irrespective of the
      treatments, a decline in P4 concentration on day 18 was observed for cows without
      P4 priming. However, animals exposed to P4 priming, treated with EB maintained
      high P4 concentrations (8.8 +/- 1.2 ng/ml), whereas there was a decline in P4 on
      day 18 (2.1 +/- 1.0 ng/ml) for cows that received GnRH to induce ovulation (p <
      0.01). Production of 13,14-dihydro-15-keto prostaglandin F(2)alpha (PGFM) in
      response to OT increased between days 9 and 18 (p < 0.01), and this increase
      tended to be more evident in animals not exposed to P4 priming (p < 0.06). In
      conclusion, the increase in E2 during the pre-ovulatory period was not effective
      in inhibiting PGFM release, which was lower in P4-primed than in non-primed
      animals. Treatment with EB promoted the maintenance of elevated P4 concentrations
      18 days after ovulation in P4-primed animals, indicating a possible beneficial
      effect of hormone protocols containing EB in animals with P4 priming.

PMID- 19392667
TI  - Allotransplantation of transgenic mouse ovaries expressing enhanced green
      fluorescent protein under the control of the murine phosphoglycerate kinase 1
      promoter.
AB  - The aim of this study was to generate a transgenic mouse that ubiquitously
      expressed enhanced green fluorescent protein (EGFP) under the control of the
      murine phosphoglycerate kinase 1 promoter by allotransplantation of transgenic
      mouse ovaries. The EGFP transgenic mice expressed green fluorescence in many
      organs, and the fluorescence was detected as early as the embryonic stage.
      Ovaries from the EGFP transgenic mice were allotransplanted into recipients and
      these mice were mated with normal male mice. Histological sections of EGFP
      allotransplanted ovaries from the recipient mice showed the well development and
      formation at follicles and corpora lutea. The green fluorescence was clearly
      detectable at the allotransplanted section of the ovaries, which had fused with
      the normal ovary. The average size of the first litter from these mice was 6.8 +/
      1.2 pups per recipient, and 17.8% of the pups expressed EGFP. These results
      demonstrated that allotransplantation of transgenic ovaries can restore a normal
      reproductive lifespan and can be used to generate a ubiquitously expressing EGFP
      animal model.

PMID- 19392669
TI  - Effects of ethanol on synthesis of prostaglandin F2alpha in bovine females.
AB  - Ethanol stimulates the production of prostaglandins in many species. The purpose
      of this study was to verify the effect of ethanol on the production of
      prostaglandin F2alpha (PGF2alpha) and luteolysis in bovine females. In the first
      experiment, Holstein cows at day 17 of the oestrous cycle were treated with 100%
      ethanol (0.05 ml/kg of body weight, IV; n = 5), saline (0.05 ml/kg of body
      weight, IV; n = 4) or synthetic prostaglandin (150 MUg of D-cloprostenol/cow, IM;
      n = 4). The plasma concentrations of 13, 14-dihydro-15-keto PGF2alpha (PGFM; the
      main metabolite of PGF2alpha measured in the peripheral blood) were assessed by
      radioimmunoassay (RIA). There was an acute release of PGFM in response to ethanol
      comparing to other treatments (p <= 0.05). However, only cows treated with
      PGF2alpha underwent luteolysis. In the second experiment, endometrial explants of
      cross-bred beef cows (n = 4) slaughtered at day 17 of the oestrous cycle were
      cultured for 4 h. During the last 3 h, the explants were cultured with medium
      supplemented with 0, 0.1, 1, 10 or 100 MUl of 100% ethanol/ml. Medium samples
      were collected at hours 1 and 4 and concentrations of PGF2alpha were measured by
      RIA. Ethanol did not induce PGF2alpha production by the endometrium. In
      conclusion, ethanol does not cause luteolysis in cows because it stimulates
      production of PGF2alpha in extra-endometrial tissues.

PMID- 19392670
TI  - Efficiency of SCNT buffalo (Bubalus bubalis) embryos in different culture medium
      and analysis of mRNA expression of insulin-like growth factors during
      embryogenesis.
AB  - Growth factors in culture media are known to affect the embryo production rates
      in in vitro production cultures. To improve the efficiency of somatic cell
      nuclear transfer (SCNT) derived embryos in Indian buffaloes (Bubalus bubalis),
      embryos were cultured in three different culture mediums viz. Group-A; TCM-199 +
      FBS, Group-B; TCM-199 + Poly vinyl alcohol (PVA) and Group-C; CR1aa + BSA. Embryo
      production rate and expression level of insulin-like growth factor genes (IGF-1,
      IGF-1R, IGF-2 and IGF-2R) were analysed in embryo culture. Cleavage and
      blastocyst production rates were 62.5% and 22.3% in Group-A, 53.8% and 13.0% in
      Group-B and 62.0% and 19.2% in Group-C respectively, whereas in in vitro
      fertilization (IVF) control cultured in TCM-199 plus 10% FBS, rates were 79.1%
      and 29.4%. Relative gene expression of SCNT embryos was compared with that in IVF
      control. IGF-1 and IGF-2 mRNA expression at blastocyst stage was up-regulated (p
      <= 0.05) in all culture groups, while IGF-1R and IGF-2R expression was down
      regulated (p <= 0.05) in Group-B and Group-C. In conclusion, the higher mRNA
      levels at certain stages in different culture conditions affected in vitro
      development of SCNT embryos. These results show that the transcript level of the
      insulin-like growth factor genes was significantly altered by in vitro culture
      condition. Culture medium TCM-199 with 10% FBS produced higher number of embryos
      and was able to co-op with gene expression of IVF control. Differences continue
      to be observed between SCNT cultured and IVF embryos, and until these differences
      are minimized, aberrations in SCNT embryonic development will continue to arise.

PMID- 19392671
TI  - Late abscess formation caused by silk suture following hysterectomy in a female
      dog.
AB  - A 5-year-old female cross-breed dog was presented for a one-month history of
      lethargy, poor appetite and weight loss. A hysterectomy had been performed 2
      years ago. Abdominal palpation revealed a mid-abdominal mass and haematological
      analysis showed leucocytosis with left shift. On abdominal radiographs, a 9 cm in
      diameter soft tissue opacity mass ventral to the colon and caudal to the left
      kidney was observed. The abdominal ultrasonography revealed a mass well
      circumscribed, with a hyperechoic capsule and hypoechoic center with echoic
      debris. The presumptive diagnosis was an abscess due to foreign body granuloma.
      Laparotomy was performed and a mass close to the left ovary was found. Adhesions
      and residues of the suture material were observed close to the right ovary and
      the uterine body stump. The mass, both ovaries and adhesions were removed. On cut
      section of the mass two cavities were observed. The small one contained three
      embedded silk suture residues. Histopathological examination confirmed the
      diagnosis of a chronic abscess caused by silk suture.

PMID- 19392672
TI  - Phthalate exposure through food and consumers' risk perception of chemicals in
      food.
AB  - Phthalates have been detected in various types of retail foods. Consumers'
      exposure to phthalates is common. Consumers are concerned about chemicals in
      food. Our aim was to investigate the relationships between consumers' exposure to
      phthalates through food, consumers' interest in a natural and healthy diet, risk
      perception of food chemicals, and consumers' diet patterns. We collected data
      through a mail survey in the adult Swiss-German population (N = 1,200). We
      modeled exposure to di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP),
      benzyl butyl phthalate (BBP), and diethyl phthalate (DEP) based on a food
      frequency questionnaire and phthalate concentrations reported from food surveys.
      Using rating scales, we assessed risk perceptions of chemicals in food and
      interest in a natural and healthy diet. Higher risk perceptions and higher
      natural and healthy diet interest were associated with higher daily doses of
      DEHP, BBP, and DEP. No health risk from phthalates in food was identified for the
      vast majority of the population. Four consumers' diet clusters were discerned,
      with differences in phthalate exposure, risk perceptions, and interest in a
      natural and healthy diet. This study shows that even those consumers who express
      strong interest in natural food and low acceptance of food chemicals, and who try
      to make respective food choices, are exposed to contaminants such as phthalates.

PMID- 19392673
TI  - Assessing infection control measures for pandemic influenza.
AB  - We construct a mathematical model of aerosol (i.e., droplet-nuclei) transmission
      of influenza within a household containing one infected and embed it into an
      epidemic households model in which infecteds occasionally infect someone from
      another household; in a companion paper, we argue that the contribution from
      contact transmission is trivial for influenza and the contribution from droplet
      transmission is likely to be small. Our model predicts that the key infection
      control measure is the use of N95 respirators, and that the combination of
      respirators, humidifiers, and ventilation reduces the threshold parameter (which
      dictates whether or not an epidemic breaks out) by approximately 20% if 70% of
      households comply, and by approximately 40% if 70% of households and workplaces
      comply (approximately 28% reduction would have been required to control the 1918
      pandemic). However, only approximately 30% of the benefits in the household are
      achieved if these interventions are used only after the infected develops
      symptoms. It is also important for people to sleep in separate bedrooms
      throughout the pandemic, space permitting. Surgical masks with a device (e.g.,
      nylon hosiery) to reduce face-seal leakage are a reasonable alternative to N95
      respirators if the latter are in short supply.

PMID- 19392674
TI  - Hot potato: expert-consumer differences in the perception of a second-generation
      novel food.
AB  - Novel foods have been the object of intense public debate in recent years.
      Despite widespread efforts to communicate the outcomes of risk assessments to
      consumers, public confidence in risk management has been low. Social scientists
      have identified various reasons for this, including a disagreement between
      technical experts and consumers over the nature of the hazards on which risk
      assessments should focus. The aim of this study was to identify and compare the
      ways in which experts and consumers understand the benefits and risks associated
      with a genetically modified example crop. Two qualitative studies were conducted.
      In Study 1, mental models were elicited from 24 experts by means of a three-wave
      Delphi procedure. In Study 2, mental models were elicited from 25 consumers by
      means of in-depth interviews. As expected, the expert mental models were focused
      on the types of hazards that can realistically be addressed under current
      regulatory frameworks, whereas the consumers were often more concerned about
      issues outside the scope of current legislation. Moreover, the experts tended to
      define risk and benefit in terms of detailed chains of cause-effect relationships
      between variables for which clear definitions and measurement rules exist. The
      concepts the consumers used when reasoning about biological processes were very
      abstract, suggesting that the participants had, at most, a holistic
      understanding. In line with this, issues of uncertainty played a prominent role
      for the consumers.

PMID- 19392675
TI  - Public perceptions of Florida red tide risks.
AB  - This research integrates theoretical frameworks of risk perception, social
      amplification of risk, and the role of place-specific contexts in order to
      explore the various perceptions surrounding Florida red tides. Florida red tides
      are naturally occurring events that are increasing in frequency, duration, and
      severity. This has implications for public health, the local economy, and
      ecosystem health. While many of the negative impacts of Florida red tides are not
      easily controlled, some of the secondary impacts may be mitigated through
      individuals' responses. However, public perception and consequent reactions to
      Florida red tides have not been investigated. This research uses questionnaire
      surveys, and semi-structured interviews, to explore the various perceptions of
      the risk surrounding red tides. Surveys and interviews were conducted along two
      Florida west coast beaches. The results indicate that the underlying foundations
      of the social amplification of the risk framework are applicable to understanding
      how individuals form perceptions of risk relative to red tide events. There are
      key differences between the spatial locations of individuals and corresponding
      perceptions, indicating that place-specific contexts are essential to
      understanding how individuals receive and interpret risk information. The results
      also suggest that individuals may be lacking efficient and up-to-date information
      about Florida red tides and their impacts because of inconsistent public
      outreach. Overall, social and spatial factors appear to be influential as to
      whether individuals amplify or attenuate the risks associated with Florida red
      tides.

PMID- 19392676
TI  - Uncertainty and variability in health-related damages from coal-fired power
      plants in the United States.
AB  - The health-related damages associated with emissions from coal-fired power plants
      can vary greatly across facilities as a function of plant, site, and population
      characteristics, but the degree of variability and the contributing factors have
      not been formally evaluated. In this study, we modeled the monetized damages
      associated with 407 coal-fired power plants in the United States, focusing on
      premature mortality from fine particulate matter (PM(2.5)). We applied a reduced
      form chemistry-transport model accounting for primary PM(2.5) emissions and the
      influence of sulfur dioxide (SO(2)) and nitrogen oxide (NO(x)) emissions on
      secondary particulate formation. Outputs were linked with a concentration
      response function for PM(2.5)-related mortality that incorporated nonlinearities
      and model uncertainty. We valued mortality with a value of statistical life
      approach, characterizing and propagating uncertainties in all model elements. At
      the median of the plant-specific uncertainty distributions, damages across plants
      ranged from $30,000 to $500,000 per ton of PM(2.5), $6,000 to $50,000 per ton of
      SO(2), $500 to $15,000 per ton of NO(x), and $0.02 to $1.57 per kilowatt-hour of
      electricity generated. Variability in damages per ton of emissions was almost
      entirely explained by population exposure per unit emissions (intake fraction),
      which itself was related to atmospheric conditions and the population size at
      various distances from the power plant. Variability in damages per kilowatt-hour
      was highly correlated with SO(2) emissions, related to fuel and control
      technology characteristics, but was also correlated with atmospheric conditions
      and population size at various distances. Our findings emphasize that control
      strategies that consider variability in damages across facilities would yield
      more efficient outcomes.

PMID- 19392677
TI  - How bad can a crisis be if it does not top the news?
AB  - Sudden onset of front-page news about the U.S. financial crisis, beginning
      September 6, 2008, may have exacerbated underlying financial problems and
      facilitated the spread of risk panic to other nations.

PMID- 19392678
TI  - Development of a quantitative microbial risk assessment for human salmonellosis
      through household consumption of fresh minced pork meat in Belgium.
AB  - A quantitative microbial risk assessment (QMRA) according to the Codex
      Alimentarius Principles is conducted to evaluate the risk of human salmonellosis
      through household consumption of fresh minced pork meat in Belgium. The
      quantitative exposure assessment is carried out by building a modular risk model,
      called the METZOON-model, which covers the pork production from farm to fork. In
      the METZOON-model, the food production pathway is split up in six consecutive
      modules: (1) primary production, (2) transport and lairage, (3) slaughterhouse,
      (4) postprocessing, (5) distribution and storage, and (6) preparation and
      consumption. All the modules are developed to resemble as closely as possible the
      Belgian situation, making use of the available national data. Several statistical
      refinements and improved modeling techniques are proposed. The model produces
      highly realistic results. The baseline predicted number of annual salmonellosis
      cases is 20,513 (SD 9061.45). The risk is estimated higher for the susceptible
      population (estimate 4.713 x 10(-5); SD 1.466 x 10(-5)) compared to the normal
      population (estimate 7.704 x 10(-6); SD 5.414 x 10(-6)) and is mainly due to
      undercooking and to a smaller extent to cross-contamination in the kitchen via
      cook's hands.

PMID- 19392679
TI  - Trust, confidence, and the 2008 global financial crisis.
AB  - The 2008 global financial crisis has been compared to a "once-in-a-century credit
      tsunami," a disaster in which the loss of trust and confidence played key
      precipitating roles and the recovery from which will require the restoration of
      these crucial factors. Drawing on the analogy between the financial crisis and
      environmental and technological hazards, recent research on the role of trust and
      confidence in the latter is used to provide a perspective on the former. Whereas
      "trust" and "confidence" are used interchangeably and without explicit definition
      in most discussions of the financial crisis, this perspective uses the TCC model
      of cooperation to clearly distinguish between the two and to demonstrate how this
      distinction can lead to an improved understanding of the crisis. The roles of
      trust and confidence-both in precipitation and in possible recovery-are discussed
      for each of the three major sets of actors in the crisis, the regulators, the
      banks, and the public. The roles of trust and confidence in the larger context of
      risk management are also examined; trust being associated with political
      approaches, confidence with technical. Finally, the various stances that
      government can take with regard to trust-such as supportive or skeptical-are
      considered. Overall, it is argued that a clear understanding of trust and
      confidence and a close examination of the specific, concrete circumstances of a
      crisis-revealing when either trust or confidence is appropriate-can lead to
      useful insights for both recovery and prevention of future occurrences.

PMID- 19392680
TI  - Evaluation of diquat against an acute experimental infection of Flavobacterium
      columnare in channel catfish, Ictalurus punctatus (Rafinesque).
AB  - A trial was performed to evaluate the efficacy of diquat (6,7-dihydrodipyrido[1,2
      a:2',1'-c]pyrazinediium dibromide) against an acute experimental infection of
      Flavobacterium columnare in channel catfish, Ictalurus punctatus. Diquat is an
      Environmental Protection Agency-approved herbicide and has the potential to be
      legally and practically used against columnaris. Channel catfish were challenged,
      by cutaneous abrasion, and waterborne exposure to F. columnare and treated once
      at 22-h post-challenge with 2.5, 5.0, 10.0 and 15 mg L(-1) of diquat active
      ingredient for 6 h. At the conclusion of the trial, 21-day post-challenge, diquat
      at 5.0, 10.0 and 15 mg L(-1) significantly (P < 0.05) reduced the mortality of
      infected fish from 95% in the challenged non-treated fish to 68%, 59% and 49%,
      respectively. In vitro, the minimum inhibitory concentration (MIC) of 23 isolates
      of F. columnare was assayed. The majority of the isolates had an MIC value of 5
      microg mL(-1) (15 of the 23 isolates). Infected fish exhibited acute clinical
      signs similar to a natural infection. The skin had severe ulcerative necrotizing
      dermatitis and the muscles had severe necrotizing myositis. The gills had severe
      multifocal necrotizing branchitis. The results demonstrate that diquat would
      reduce mortalities caused by an acute columnaris infection.

PMID- 19392681
TI  - Detection and identification of aquatic mycobacteria in formalin-fixed, paraffin
      embedded fish tissues.
AB  - The isolation of mycobacteria from field samples is problematic, and isolation of
      the bacterium is sometimes not even attempted. The detection of mycobacteria
      through traditional histology using formalin-fixed, paraffin-embedded (FFPE)
      tissues is neither sensitive nor specific. However, detection of mycobacterial
      DNA from FFPE specimens, suspected of being infected with mammalian
      mycobacteriosis, is a routine clinical procedure. In the present study, a
      polymerase chain reaction (PCR)-based method was used to detect and identify
      mycobacteria in FFPE specimens sampled from fish suspected of being infected with
      fish mycobacteriosis. A total of 45 fish tissue samples, comprising of 12 tissue
      samples obtained from experimentally infected fish and the remainder from fish
      naturally infected with mycobacteria, were analysed using a PCR protocol which
      amplifies a fragment of the mycobacterial 65 kDa heat-shock protein (hsp65) gene.
      PCR-restriction enzyme analysis and/or sequencing were employed to further
      analyse the PCR amplicons. The PCR results were compared with those obtained by
      histology and culture. Mycobacterial DNA was detected in 34 of the 45 samples
      examined, of which 16 samples (47%) showed granulomatous reactions on
      histological examination. Using histology as the gold standard, no false-negative
      PCR results were obtained. Also, considering the presence or absence of
      granulomas as a diagnostic criterion, the sensitivity and specificity of PCR in
      42 of the FFPE tissues were 16/16 (100%) and 8/26 (approximately 30.8%),
      respectively. Corresponding microbiological cultures were available for 15 cases,
      of which 13 were pure Mycobacterium cultures. Of these, 13 were PCR positive
      (100% sensitivity and 50% specificity). The PCR-based methods used here proved
      sensitive, specific and rapid for the detection of mycobacteria in routinely
      processed paraffin wax-embedded and formalin-fixed histological samples, and the
      results of the study suggest that this method has potential use in retrospective
      epidemiological studies.

PMID- 19392682
TI  - Nodavirus provokes subclinical encephalitis and retinochoroiditis in adult farmed
      Atlantic cod, Gadus morhua L.
AB  - Viral nervous necrosis (VNN) caused by beta-nodavirus affects many species of
      farmed marine fish, in particular juveniles. Apparently healthy, normally
      feeding, adult farmed Atlantic cod, Gadus morhua, were sampled in a farm 14
      months after an outbreak of VNN with clinical signs. Following necropsy, brain
      and eye tissues were examined by histology, immunohistochemistry and polymerase
      chain reaction (PCR). Nodavirus-provoked cell death and inflammation was detected
      in eye and brain, particularly in the retina and cerebellum and differed from
      that previously described in Atlantic cod during clinical stages of VNN. Virus
      was detected both by PCR and immunohistochemistry. This is, to the best of our
      knowledge, the first description of pathological changes associated with chronic
      subclinical nodavirus infection in Atlantic cod. Our observations suggest that
      severe infection and pathological changes may go undetected if investigations are
      restricted to clinical examination and macroscopic evaluation at necropsy.

PMID- 19392683
TI  - Experimental study of the susceptibility of Atlantic cod, Gadus morhua (L.), to
      infection with an IPNV strain pathogenic for Atlantic salmon, Salmo salar L.
AB  - Intraperitoneal (IP) injection, cohabitation and immersion routes of infection
      were used to determine if Atlantic cod, Gadus morhua (L.), of 1 and 3 g are
      susceptible to infectious pancreatic necrosis (IPN). Mortalities of cod injected
      IP were significantly higher when challenged with infectious pancreatic necrosis
      virus (IPNV) than with phosphate buffered saline. This is the first report of
      Atlantic cod mortalities caused by IPNV. Fish challenged by cohabitation had
      significantly higher mortalities than the controls, but mortalities of Atlantic
      cod challenged with IPNV by immersion were not significantly different from
      controls. Titres of IPNV in the tissues of infected fish were sometimes very high
      (range 10(2)-10(10) infectious units per gram of tissue) suggesting virus
      replication and titres of fish that died were generally higher than those of fish
      which survived. However, the relatively low mortality rates when challenged by
      cohabitation and immersion (20% and 17%, respectively), compared to the IP
      injection challenge (100%) suggest that 1 and 3 g cod have low susceptibility to
      IPN when challenged by more natural routes. These data strongly suggest that the
      cause of death of experimentally challenged cod was IPNV and further histological
      evidence for this came from 1 g cod challenged IP with IPNV in which the pancreas
      showed severe necrosis and heavy immunostaining for IPNV coincidentally with the
      peak of mortalities.

PMID- 19392684
TI  - Salmonid alphavirus associated with Lepeophtheirus salmonis (Copepoda: Caligidae)
      from Atlantic salmon, Salmo salar L.

PMID- 19392685
TI  - The cell morphogenesis gene SPIRRIG in Arabidopsis encodes a WD/BEACH domain
      protein.
AB  - WD40/BEACH domain proteins have been implicated in membrane trafficking and
      membrane composition events in Dictyostelium and Drosophila. In this paper, we
      show that the Arabidopsis SPIRRIG (SPI) gene encodes a WD40/BEACH domain protein.
      The cellular analysis revealed fragmented vacuoles in root hairs similar to those
      found in the corresponding Dictyostelium mutants, suggesting a related cellular
      function. The phenotypic analysis revealed that spi mutants share all phenotypic
      aspects of mutants in the actin polymerization-regulating ARP2/3 pathway,
      including distorted trichomes, less lobing of epidermal pavement cells,
      disconnected epidermal cells on various organs, and shorter root hairs. This
      complete phenotypic overlap suggests that this WD40/BEACH domain protein and the
      actin-regulating ARP2/3 pathway are involved in similar growth processes.

PMID- 19392686
TI  - Novel lycopene epsilon cyclase activities in maize revealed through perturbation
      of carotenoid biosynthesis.
AB  - In maize, human selection for yellow endosperm has led to diversification of
      grain carotenoid content and composition. This variation has remained largely
      untapped in modern breeding programs that have focused nearly exclusively on
      yield gains. In this paper, we show that carotenoid accumulation patterns differ
      in maize embryo and endosperm tissues, and that this tissue-specific accumulation
      is largely mediated through differential expression of genes encoding lycopene
      beta-cyclase and lycopene epsilon-cyclase (LcyB and LcyE). In the absence of LCYB
      function, LCYE produces a number of unusual carotenes, including delta-carotene,
      epsilon-carotene and lactucaxanthin (epsilon,epsilon-carotene-3,3'-diol), in
      endosperm tissue. A similar carotene cyclization profile is seen when LcyE is
      introduced into lycopene-accumulating Escherichia coli cells, suggesting that the
      carotenoid profile in the endosperm tissue of the lcyB mutant is largely due to
      the activity of LCYE in the absence of LCYB. Using site-directed mutagenesis of
      LcyE, critical amino acids were defined that regulate the product specificity of
      the enzyme. Finally, we show that several genes encoding enzymes in isoprenoid
      and carotenoid biosynthesis are probably subject to negative transcriptional
      regulation, mediated by a carotenoid or a molecule derived from a carotenoid. The
      implications of these findings with respect to breeding for carotenoid
      composition in maize grain are discussed.

PMID- 19392687
TI  - Quantitative measurement of specific biomarkers for protein oxidation, nitration
      and glycation in Arabidopsis leaves.
AB  - Higher plants are continually exposed to reactive oxygen and nitrogen species
      during their lives. Together with glucose and reactive dicarbonyls, these can
      modify proteins spontaneously, leading to protein oxidation, nitration and
      glycation. These reactions have the potential to damage proteins and have an
      impact on physiological processes. The levels of protein oxidation, nitration and
      glycation adducts were assayed, using liquid chromatography coupled with tandem
      mass spectrometry, in total leaf extracts over a diurnal cycle and when exposed
      to conditions that promote oxidative stress. Changes in the levels of oxidation,
      glycation and nitration adducts were found between the light and dark phases
      under non-stress conditions. A comparison between wild-type plants and a mutant
      lacking peptide methionine sulfoxide reductase (pmsr2-1) showed increased protein
      oxidation, nitration and glycation of specific amino acid residues during
      darkness in pmsr2-1. Short-term excess light exposure, which promoted oxidative
      stress, led to increased protein glycation, specifically by glyoxal. This
      suggested that any increased oxidative damage to proteins was within the repair
      capacity of the plant. The methods developed here provide the means to
      simultaneously detect a range of protein oxidation, nitration and glycation
      adducts within a single sample. Thus, these methods identify a range of
      biomarkers to monitor a number of distinct biochemical processes that have an
      impact on the proteome and therefore the physiological state of the plant.

PMID- 19392688
TI  - Super-stretched pachytene chromosomes for fluorescence in situ hybridization
      mapping and immunodetection of DNA methylation.
AB  - Meiotic pachytene chromosome-based fluorescence in situ hybridization (FISH)
      mapping is one of the most important tools in plant molecular cytogenetic
      research. Here we report a simple technique that allows stretching of pachytene
      chromosomes of maize to up to at least 20 times their original size. A modified
      Carnoy's II fixative (6:1:3 ethanol:chloroform:acetic acid) was used in the
      procedure, and proved to be key for super-stretching of pachytene chromosomes. We
      demonstrate that super-stretched pachytene chromosomes provide unprecedented
      resolution for chromosome-based FISH mapping. DNA probes separated by as little
      as 50 kb can be resolved on super-stretched chromosomes. A combination of FISH
      with immunofluorescent detection of 5-methyl cytosine on super-stretched
      pachytene chromosomes provides a powerful tool to reveal DNA methylation of
      specific chromosomal domains, especially those associated with highly repetitive
      DNA sequences.

PMID- 19392689
TI  - The Arabidopsis ABA-INSENSITIVE (ABI) 4 factor acts as a central transcription
      activator of the expression of its own gene, and for the induction of ABI5 and
      SBE2.2 genes during sugar signaling.
AB  - The transcription factor ABA INSENSITIVE 4 (ABI4), discovered nearly 10 years
      ago, plays a central role in a variety of functions in plants, including sugar
      responses. However, not until very recently has its mechanism of action begun to
      be elucidated. Modulating gene expression is one of the primary mechanisms of
      sugar regulation in plants. Nevertheless, the transcription factors involved in
      regulating sugar responses and their role(s) during the signal transduction
      cascade remain poorly defined. In this paper we analyzed the participation of
      ABI4, as it is one of the main transcription factors implicated in glucose
      signaling during early seedling development. Our studies show that ABI4 is an
      essential activator of its own expression during development, in ABA signaling
      and in sugar responses. It is also important for the glucose-mediated expression
      of the genes ABI5 and SBE2.2. We demonstrate that ABI4 binds directly to the
      promoter region of all three genes and activates their expression in vivo through
      at CE1-like element. Previous studies found that ABI4 also functions as a
      transcriptional repressor of sugar-regulated genes, therefore this transcription
      factor is a versatile protein with dual functions for modulating gene expression.

PMID- 19392690
TI  - Antagonism between salicylic and abscisic acid reflects early host-pathogen
      conflict and moulds plant defence responses.
AB  - The importance of phytohormone balance is increasingly recognized as central to
      the outcome of plant-pathogen interactions. Recently it has been demonstrated
      that abscisic acid signalling pathways are utilized by the bacterial
      phytopathogen Pseudomonas syringae to promote pathogenesis. In this study, we
      examined the dynamics, inter-relationship and impact of three key acidic
      phytohormones, salicylic acid, abscisic acid and jasmonic acid, and the bacterial
      virulence factor, coronatine, during progression of P. syringae infection of
      Arabidopsis thaliana. We show that levels of SA and ABA, but not JA, appear to
      play important early roles in determining the outcome of the infection process.
      SA is required in order to mount a full innate immune responses, while bacterial
      effectors act rapidly to activate ABA biosynthesis. ABA suppresses inducible
      innate immune responses by down-regulating SA biosynthesis and SA-mediated
      defences. Mutant analyses indicated that endogenous ABA levels represent an
      important reservoir that is necessary for effector suppression of plant-inducible
      innate defence responses and SA synthesis prior to subsequent pathogen-induced
      increases in ABA. Enhanced susceptibility due to loss of SA-mediated basal
      resistance is epistatically dominant over acquired resistance due to ABA
      deficiency, although ABA also contributes to symptom development. We conclude
      that pathogen-modulated ABA signalling rapidly antagonizes SA-mediated defences.
      We predict that hormonal perturbations, either induced or as a result of
      environmental stress, have a marked impact on pathological outcomes, and we
      provide a mechanistic basis for understanding priming events in plant defence.

PMID- 19392691
TI  - A cell wall extract from the endophytic fungus Piriformospora indica promotes
      growth of Arabidopsis seedlings and induces intracellular calcium elevation in
      roots.
AB  - Calcium (Ca2+), as a second messenger, is crucial for signal transduction
      processes during many biotic interactions. We demonstrate that cellular [Ca2+]
      elevations are early events in the interaction between the plant growth-promoting
      fungus Piriformospora indica and Arabidopsis thaliana. A cell wall extract (CWE)
      from the fungus promotes the growth of wild-type seedlings but not of seedlings
      from P. indica-insensitive mutants. The extract and the fungus also induce a
      similar set of genes in Arabidopsis roots, among them genes with Ca2+ signalling
      related functions. The CWE induces a transient cytosolic Ca2+ ([Ca2+](cyt))
      elevation in the roots of Arabidopsis and tobacco (Nicotiana tabacum) plants, as
      well as in BY-2 suspension cultures expressing the Ca2+ bioluminescent indicator
      aequorin. Nuclear Ca2+ transients were also observed in tobacco BY-2 cells. The
      Ca2+ response was more pronounced in roots than in shoots and involved Ca2+
      uptake from the extracellular space as revealed by inhibitor studies. Inhibition
      of the Ca2+ response by staurosporine and the refractory nature of the Ca2+
      elevation suggest that a receptor may be involved. The CWE does not stimulate
      H2O2 production and the activation of defence gene expression, although it led to
      phosphorylation of mitogen-activated protein kinases (MAPKs) in a Ca2+-dependent
      manner. The involvement of MAPK6 in the mutualistic interaction was shown for an
      mpk6 line, which did not respond to P. indica. Thus, Ca2+ is likely to be an
      early signalling component in the mutualistic interaction between P. indica and
      Arabidopsis or tobacco.

PMID- 19392692
TI  - Arabidopsis plant homeodomain finger proteins operate downstream of auxin
      accumulation in specifying the vasculature and primary root meristem.
AB  - In Arabidopsis thaliana, auxin is a key regulator of tissue patterning in the
      developing embryo. We have identified a group of proteins that act downstream of
      auxin accumulation in auxin-mediated root and vascular development in the embryo.
      Combined mutations in OBERON1 (OBE1) and OBERON2 (OBE2) give rise to obe1 obe2
      double mutant seedlings that closely phenocopy the monopteros (mp) mutant
      phenotype, with an absence of roots and defective development of the vasculature.
      We show that, in contrast to the situation in mp mutants, obe1 obe2 double mutant
      embryos show auxin maxima at the root pole and in the provascular region, and
      that the SCF(TIR1) pathway, which translates auxin accumulation into
      transcriptional activation of auxin-responsive genes, remains intact. Although we
      focus on the impact of obe mutations on aspects of embryo development, the effect
      of such mutations on a broad range of auxin-related gene expression and the
      tissue expression patterns of OBE genes in seedlings suggest that OBE proteins
      have a wider role to play in growth and development. We suggest that OBE1 and
      OBE2 most likely control the transcription of genes required for auxin responses
      through the action of their PHD finger domains.

PMID- 19392693
TI  - Developmental complexity of arabinan polysaccharides and their processing in
      plant cell walls.
AB  - Plant cell walls are constructed from a diversity of polysaccharide components.
      Molecular probes directed to structural elements of these polymers are required
      to assay polysaccharide structures in situ, and to determine polymer roles in the
      context of cell wall biology. Here, we report on the isolation and the
      characterization of three rat monoclonal antibodies that are directed to 1,5
      linked arabinans and related polymers. LM13, LM16 and LM17, together with LM6,
      constitute a set of antibodies that can detect differing aspects of arabinan
      structures within cell walls. Each of these antibodies binds strongly to isolated
      sugar beet arabinan samples in ELISAs. Competitive-inhibition ELISAs indicate the
      antibodies bind differentially to arabinans with the binding of LM6 and LM17
      being effectively inhibited by short oligoarabinosides. LM13 binds preferentially
      to longer oligoarabinosides, and its binding is highly sensitive to arabinanase
      action, indicating the recognition of a longer linearized arabinan epitope. In
      contrast, the binding of LM16 to branched arabinan and to cell walls is increased
      by arabinofuranosidase action. The presence of all epitopes can be differentially
      modulated in vitro using glycoside hydrolase family 43 and family 51
      arabinofuranosidases. In addition, the LM16 epitope is sensitive to the action of
      beta-galactosidase. Immunofluorescence microscopy indicates that the antibodies
      can be used to detect epitopes in cell walls, and that the four antibodies reveal
      complex patterns of epitope occurrence that vary between organs and species, and
      relate both to the probable processing of arabinan structural elements and the
      differing mechanical properties of cell walls.

PMID- 19392694
TI  - Signal signature of aboveground-induced resistance upon belowground herbivory in
      maize.
AB  - Plants activate local and systemic defence mechanisms upon exposure to stress.
      This innate immune response is partially regulated by plant hormones, and
      involves the accumulation of defensive metabolites. Although local defence
      reactions to herbivores are well studied, less is known about the impact of root
      herbivory on shoot defence. Here, we examined the effects of belowground
      infestation by the western corn rootworm Diabrotica virgifera virgifera on
      aboveground resistance in maize. Belowground herbivory by D. v. virgifera induced
      aboveground resistance against the generalist herbivore Spodoptera littoralis,
      and the necrotrophic pathogen Setosphaeria turcica. Furthermore, D. v. virgifera
      increased shoot levels of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA),
      and primed the induction of chlorogenic acid upon subsequent infestation by S.
      littoralis. To gain insight into the signalling network behind this below- and
      aboveground defence interaction, we compiled a set of 32 defence-related genes,
      which can be used as transcriptional marker systems to detect activities of
      different hormone-response pathways. Belowground attack by D. v. virgifera
      triggered an ABA-inducible transcription pattern in the shoot. The quantification
      of defence hormones showed a local increase in the production of oxylipins after
      root and shoot infestation by D. v. virgifera and S. littoralis, respectively. On
      the other hand, ABA accumulated locally and systemically upon belowground attack
      by D. v. virgifera. Furthermore, D. v. virgifera reduced the aboveground water
      content, whereas the removal of similar quantities of root biomass had no effect.
      Our study shows that root herbivory by D. v. virgifera specifically alters the
      aboveground defence status of a maize, and suggests that ABA plays a role in the
      signalling network mediating this interaction.

PMID- 19392695
TI  - EHD2 inhibits ligand-induced endocytosis and signaling of the leucine-rich repeat
      receptor-like protein LeEix2.
AB  - Plants are constantly being challenged by aspiring pathogens. In order to protect
      themselves, plants have developed numerous defense mechanisms that are either
      specific or non-specific to the pathogen. Pattern recognition receptors can
      trigger plant defense responses in response to specific ligands or patterns. EIX
      (ethylene-inducing xylanase) triggers a defense response via the LeEix2 receptor,
      while bacterial flagellin triggers plant innate immunity via the FLS2 receptor.
      Endocytosis has been suggested to be crucial for the process in both cases. Here
      we show that the EIX elicitor triggers internalization of the LeEix2 receptor.
      Treatment with endocytosis, actin or microtubule inhibitors greatly reduced the
      internalization of LeEix2. Additionally, we demonstrate that plant EHD2 binds to
      LeEix2 and is an important factor in its internalization and in regulation of the
      induction of defense responses such as the hypersensitive response, ethylene
      biosynthesis and induction of pathogenesis-related protein expression in the case
      of EIX/LeEix2 (an LRR receptor lacking a kinase domain), but does not appear to
      be involved in the FLS2 system (an LRR receptor possessing a kinase domain). Our
      results suggest that various endocytosis pathways are involved in the induction
      of plant defense responses.

PMID- 19392696
TI  - Flow cytometric purification of Colletotrichum higginsianum biotrophic hyphae
      from Arabidopsis leaves for stage-specific transcriptome analysis.
AB  - Generation of stage-specific cDNA libraries is a powerful approach to identify
      pathogen genes that are differentially expressed during plant infection.
      Biotrophic pathogens develop specialized infection structures inside living plant
      cells, but sampling the transcriptome of these structures is problematic due to
      the low ratio of fungal to plant RNA, and the lack of efficient methods to
      isolate them from infected plants. Here we established a method, based on
      fluorescence-activated cell sorting (FACS), to purify the intracellular
      biotrophic hyphae of Colletotrichum higginsianum from homogenates of infected
      Arabidopsis leaves. Specific selection of viable hyphae using a fluorescent vital
      marker provided intact RNA for cDNA library construction. Pilot-scale sequencing
      showed that the library was enriched with plant-induced and pathogenicity-related
      fungal genes, including some encoding small, soluble secreted proteins that
      represent candidate fungal effectors. The high purity of the hyphae (94%)
      prevented contamination of the library by sequences derived from host cells or
      other fungal cell types. RT-PCR confirmed that genes identified in the FACS
      purified hyphae were also expressed in planta. The method has wide applicability
      for isolating the infection structures of other plant pathogens, and will
      facilitate cell-specific transcriptome analysis via deep sequencing and
      microarray hybridization, as well as proteomic analyses.

PMID- 19392697
TI  - Arabidopsis mitogen-activated protein kinase MPK18 mediates cortical microtubule
      functions in plant cells.
AB  - Mitogen-activated protein kinase (MAPK) signalling networks are important
      regulators of environmental responses and developmental processes in plants. To
      understand the role of MAPK signalling modules in the regulation of plant
      microtubule functions, we searched for MAPKs that interact with the dual
      specificity MAPK phosphatase, PROPYZAMIDE HYPERSENSITIVE 1 (PHS1), whose mutation
      has previously been reported to confer hypersensitivity to microtubule-disrupting
      drugs in Arabidopsis. Yeast two-hybrid assays demonstrated that PHS1 specifically
      interacts with two MAPKs, MPK12 and MPK18. Bimolecular fluorescence
      complementation (BiFC) studies confirmed that the PHS1 and MPK18 proteins are
      physically coupled, and that this interaction occurs in the cytoplasm. At the
      biochemical level, in vitro dephosphorylation assays indicated that phospho-MPK18
      can be dephosphorylated by recombinant PHS1. Mutant mpk18 seedlings show defects
      in microtubule-related functions, and have moderately stabilized microtubules.
      Absence of MPK18 in the phs1-1 background partially complements the phs1-1 root
      growth phenotypes, providing genetic evidence for involvement of MPK18 signalling
      in microtubule-related functions. We propose a model whereby the PHS1-MPK18
      signalling module is involved in a phosphorylation/dephosphorylation switch that
      regulates cortical microtubule functions.

PMID- 19392698
TI  - Calcium-dependent protein kinases regulate polarized tip growth in pollen tubes.
AB  - Calcium signals are critical for the regulation of polarized growth in many
      eukaryotic cells, including pollen tubes and neurons. In plants, the regulatory
      pathways that code and decode Ca(2+) signals are poorly understood. In
      Arabidopsis thaliana, genetic evidence presented here indicates that pollen tube
      tip growth involves the redundant activity of two Ca(2+)-dependent protein
      kinases (CPKs), isoforms CPK17 and -34. Both isoforms appear to target to the
      plasma membrane, as shown by imaging of CPK17-yellow fluorescent protein (YFP)
      and CPK34-YFP in growing pollen tubes. Segregation analyses from two independent
      sets of T-DNA insertion mutants indicate that a double disruption of CPK17 and 
      34 results in an approximately 350-fold reduction in pollen transmission
      efficiency. The near sterile phenotype of homozygous double mutants could be
      rescued through pollen expression of a CPK34-YFP fusion. In contrast, a transgene
      rescue was blocked by mutations engineered to disrupt the Ca(2+)-activation
      mechanism of CPK34 (CPK34-YFP-E465A,E500A), providing in vivo evidence linking
      Ca(2+) activation to a biological function of a CPK. While double mutant pollen
      tubes displayed normal morphology, relative growth rates for the most rapidly
      growing tubes were reduced by more than three-fold compared with wild type. In
      addition, while most mutant tubes appeared to grow far enough to reach ovules,
      the vast majority (>90%) still failed to locate and fertilize ovules. Together,
      these results provide genetic evidence that CPKs are essential to pollen fitness,
      and support a mechanistic model in which CPK17 and -34 transduce Ca(2+) signals
      to increase the rate of pollen tube tip growth and facilitate a response to
      tropism cues.

PMID- 19392699
TI  - Systematic analysis of cell-cycle gene expression during Arabidopsis development.
AB  - The steady-state distribution of cell-cycle transcripts in Arabidopsis thaliana
      seedlings was studied in a broad in situ survey to provide a better understanding
      of the expression of cell-cycle genes during plant development. The 61 core cell
      cycle genes analyzed were expressed at variable levels throughout the different
      plant tissues: 23 genes generally in dividing and young differentiating tissues,
      34 genes mostly in both dividing and differentiated tissues and four gene
      transcripts primarily in differentiated tissues. Only 21 genes had a typical
      patchy expression pattern, indicating tight cell-cycle regulation. The increased
      expression of 27 cell-cycle genes in the root elongation zone hinted at their
      involvement in the switch from cell division to differentiation. The induction of
      20 cell-cycle genes in differentiated cortical cells of etiolated hypocotyls
      pointed to their possible role in the process of endoreduplication. Of seven
      cyclin-dependent kinase inhibitor genes, five were upregulated in etiolated
      hypocotyls, suggesting a role in cell-cycle arrest. Nineteen genes were
      preferentially expressed in pericycle cells activated by auxin that give rise to
      lateral root primordia. Approximately 1800 images have been collected and can be
      queried via an online database. Our in situ analysis revealed that 70% of the
      cell-cycle genes, although expressed at different levels, show a large overlap in
      their localization. The lack of regulatory motifs in the upstream regions of the
      analyzed genes suggests the absence of a universal transcriptional control
      mechanism for all cell-cycle genes.

PMID- 19392700
TI  - Arabidopsis CER8 encodes LONG-CHAIN ACYL-COA SYNTHETASE 1 (LACS1) that has
      overlapping functions with LACS2 in plant wax and cutin synthesis.
AB  - Plant cuticle is an extracellular lipid-based matrix of cutin and waxes, which
      covers aerial organs and protects them from many forms of environmental stress.
      We report here the characterization of CER8/LACS1, one of nine Arabidopsis long
      chain acyl-CoA synthetases thought to activate acyl chains. Mutations in LACS1
      reduced the amount of wax in all chemical classes on the stem and leaf, except in
      the very long-chain fatty acid (VLCFA) class wherein acids longer than 24 carbons
      (C(24)) were elevated more than 155%. The C(16) cutin monomers on lacs1 were
      reduced by 37% and 22%, whereas the C(18) monomers were increased by 28% and 20%
      on stem and leaf, respectively. Amounts of wax and cutin on a lacs1-1 lacs2-3
      double mutant were much lower than on either parent, and lacs1-1 lacs2-3 had much
      higher cuticular permeability than either parent. These additive effects indicate
      that LACS1 and LACS2 have overlapping functions in both wax and cutin synthesis.
      We demonstrated that LACS1 has synthetase activity for VLCFAs C(20)-C(30), with
      highest activity for C(30) acids. LACS1 thus appears to function as a very long
      chain acyl-CoA synthetase in wax metabolism. Since C(16) but not C(18) cutin
      monomers are reduced in lacs1, and C(16) acids are the next most preferred acid
      (behind C(30)) by LACS1 in our assays, LACS1 also appears to be important for the
      incorporation of C(16) monomers into cutin polyester. As such, LACS1 defines a
      functionally novel acyl-CoA synthetase that preferentially modifies both VLCFAs
      for wax synthesis and long-chain (C(16)) fatty acids for cutin synthesis.

PMID- 19392701
TI  - Mutation of the rice gene PAIR3 results in lack of bivalent formation in meiosis.
AB  - Meiosis is essential for eukaryotic sexual reproduction and important for genetic
      diversity among individuals. Although a number of genes regulating homologous
      chromosome pairing and synapsis have been identified in the plant kingdom, their
      molecular basis remains poorly understood. In this study, we identified a novel
      gene, PAIR3 (HOMOLOGOUS PAIRING ABERRATION IN RICE MEIOSIS 3), required for
      homologous chromosome pairing and synapsis in rice. Two independent alleles,
      designated pair3-1 and pair3-2, were identified in our T-DNA insertional mutant
      library which could not form bivalents due to failure of homologous chromosome
      pairing and synapsis at diakinesis, resulting in sterility in both male and
      female gametes. Suppression of PAIR3 by RNAi produced similar results to the T
      DNA insertion lines. PAIR3 encodes a protein that contains putative coiled-coil
      motifs, but does not have any close homologs in other organisms. PAIR3 is
      preferentially expressed in reproductive organs, especially in pollen mother
      cells and the ovule tissues during meiosis. Our results suggest that PAIR3 plays
      a crucial role in homologous chromosome pairing and synapsis in meiosis.

PMID- 19392702
TI  - ATHB4, a regulator of shade avoidance, modulates hormone response in Arabidopsis
      seedlings.
AB  - Plants sense the presence of competing neighboring vegetation as a change in
      light quality: i.e. they sense the reduced ratio of red light to far-red light.
      The responses to shade are generally referred to as the shade avoidance syndrome
      (SAS), and involve various developmental changes intended to outgrow or
      outcompete the neighboring plants. Here, we analyze the function of ATHB4, a gene
      encoding a homeodomain-leucine zipper (HD-Zip) class-II transcription factor from
      Arabidopsis thaliana, the expression of which is rapidly and directly upregulated
      after proximity perception by the phytochrome photoreceptors. ATHB4 acts
      redundantly with other members of the HD-Zip class-II transcription factors. The
      expression of these genes is regulated by other members of the same class,
      forming a small transcriptional network of factors in which homeostasis is
      mutually controlled. Our results suggest that some members of this small gene
      subfamily can modulate SAS responses by controlling auxin, brassinosteroid and
      gibberellin molecular and/or physiological responsiveness. In particular, we
      propose ATHB4 as a new shade signaling component that participates in integrating
      shade perception and hormone-mediated growth.

PMID- 19392703
TI  - Dual functions of Nicotiana benthamiana Rae1 in interphase and mitosis.
AB  - Rae1 performs multiple functions in animal systems, acting in interphase as an
      mRNA export factor and during mitosis as a mitotic checkpoint and spindle
      assembly regulator. In this study we characterized multiple functions of Rae1 in
      plants. Virus-induced gene silencing of Nicotiana benthamiana Rae1, NbRae1, which
      encodes a protein with four WD40 repeats, resulted in growth arrest and abnormal
      leaf development. NbRae1 was mainly associated with the nuclear envelope during
      interphase, and NbRae1 deficiency caused accumulation of poly(A) RNA in the
      nuclei of leaf cells, suggesting defective mRNA export. In the shoot apex,
      depletion of NbRae1 led to reduced mitotic activities, accompanied by reduced
      cyclin-dependent kinase (CDK) activity and decreased expression of cyclin B1,
      CDKB1-1, and histones H3 and H4. The secondary growth of stem vasculature was
      also inhibited, indicating reduced cambial activities. Differentiated leaf cells
      of NbRae1-silenced plants exhibited elevated ploidy levels. Immunolabeling in BY
      2 cells showed that NbRae1 protein localized to mitotic microtubules and the cell
      plate-forming zone during mitosis, and recombinant NbRae1 directly bound to
      microtubules in vitro. Inhibition of NbRae1 expression in BY-2 cells using a beta
      estradiol-inducible RNAi system resulted in severe defects in spindle
      organization and chromosome alignment and segregation, which correlated with
      delays in cell cycle progression. Together, these results suggest that NbRae1
      plays a dual role in mRNA export in interphase and in spindle assembly in
      mitosis.

PMID- 19392704
TI  - Nuclear envelope and nuclear pore complex structure and organization in tobacco
      BY-2 cells.
AB  - The nuclear envelope (NE) is a fundamental structure of eukaryotic cells with a
      dual role: it separates two distinct compartments, and enables communication
      between them via nuclear pore complexes (NPCs). Little is known about NPCs and NE
      structural organization in plants. We investigated the structure of NPCs from
      both sides of the NE in tobacco BY-2 cells. We detected structural differences
      between the NPCs of dividing and quiescent nuclei. Importantly, we also traced
      the organizational pattern of the NPCs, and observed non-random NPC distribution
      over the nuclear surface. Lastly, we observed an organized filamentous protein
      structure that underlies the inner nuclear membrane, and interconnects NPCs. The
      results are discussed within the context of the current understanding of NE
      structure and function in higher eukaryotes.

PMID- 19392705
TI  - VERNALIZATION INSENSITIVE 3 (VIN3) is required for the response of Arabidopsis
      thaliana seedlings exposed to low oxygen conditions.
AB  - VERNALIZATION INSENSITIVE 3 (VIN3), which is required for the vernalization
      mediated epigenetic repression of FLOWERING LOCUS C (FLC) in Arabidopsis
      thaliana, is quantitatively induced in response to low temperatures. We found
      that hypoxic conditions also induce VIN3 in a quantitative manner but high salt,
      high temperatures and osmotic stress do not. Inhibition of mitochondrial
      respiration did not induce VIN3 expression, consistent with the lack of VIN3
      induction in response to other stresses that affect the rate of mitochondrial
      respiration. De novo protein synthesis is required for VIN3 induction during
      hypoxic conditions; this situation is not the case for VIN3 induction by low
      temperatures, indicating that different mechanisms act to induce VIN3 expression
      in response to cold and hypoxic conditions. Without VIN3 activity, fewer
      seedlings survived following a 72-h period of hypoxic treatment, indicating that
      VIN3 is required for the survival of Arabidopsis thaliana in response to hypoxic
      stress. Complementation of the vin3 mutant with a VIN3 transgene restored the
      wild-type response to low oxygen and confirmed the role of VIN3 in protecting
      both shoots and roots during low oxygen conditions. Loss of VIN3 protein did not
      affect the transcriptional regulation of genes known to be important in the
      response to low oxygen stress, which suggests that there is a novel mechanism to
      combat hypoxia that involves VIN3. This mechanism is likely to involve chromatin
      remodelling and may be similar to the role of VIN3 in the epigenetic repression
      of FLC during the vernalization response.

PMID- 19392706
TI  - AAP1 regulates import of amino acids into developing Arabidopsis embryos.
AB  - The embryo of Arabidopsis seeds is symplasmically isolated from the surrounding
      seed coat and endosperm, and uptake of nutrients from the seed apoplast is
      required for embryo growth and storage reserve accumulation. With the aim of
      understanding the importance of nitrogen (N) uptake into developing embryos, we
      analysed two mutants of AAP1 (At1g58360), an amino acid transporter that was
      localized to Arabidopsis embryos. In mature and desiccated aap1 seeds the total N
      and carbon content was reduced while the total free amino acid levels were
      strongly increased. Separately analysed embryos and seed coats/endosperm of
      mature seeds showed that the elevated amounts in amino acids were caused by an
      accumulation in the seed coat/endosperm, demonstrating that a decrease in uptake
      of amino acids by the aap1 embryo affects the N pool in the seed coat/endosperm.
      Also, the number of protein bodies was increased in the aap1 endosperm,
      suggesting that the accumulation of free amino acids triggered protein synthesis.
      Analysis of seed storage compounds revealed that the total fatty acid content was
      unchanged in aap1 seeds, but storage protein levels were decreased. Expression
      analysis of genes of seed N transport, metabolism and storage was in agreement
      with the biochemical data. In addition, seed weight, as well as total silique and
      seed number, was reduced in the mutants. Together, these results demonstrate that
      seed protein synthesis and seed weight is dependent on N availability and that
      AAP1-mediated uptake of amino acids by the embryo is important for storage
      protein synthesis and seed yield.

PMID- 19392707
TI  - High frequency of single-copy T-DNA transformants produced by floral dip in CRE
      expressing Arabidopsis plants.
AB  - For genetic transformation of plants, floral dip with Agrobacterium often results
      in integration of multiple T-DNA copies at a single locus and frequently in low
      and unstable transgene expression. To obtain efficient single-copy T-DNA
      transformants, two CRE/loxP recombinase-based simplifying strategies for complex
      T-DNA loci were compared. A T-DNA vector with oppositely oriented loxP sites was
      transformed into CRE-expressing and wild-type control Arabidopsis thaliana
      plants. Of the primary CRE-expressing transformants, 55% harboured a single copy
      of the introduced T-DNA, but only 15% in the wild-type plants. However, 73% of
      the single-copy transformants in the CRE background showed continuous somatic
      inversion of the DNA segment between the two loxP sites. To avoid inversion of
      the loxP-flanked T-DNA segment, two T-DNA vectors harbouring only one loxP site
      were investigated for their suitability for CRE/loxP recombinase-mediated
      resolution upon floral-dip transformation into CRE-expressing plants. On average,
      70% of the transformants in the CRE background were single-copy transformants,
      whereas the single-copy T-DNA frequency was only 11% for both vectors in the wild
      type background. Both resolution strategies yielded mostly Cre transformants in
      which the 35S-driven transgene expression was stable and uniform in the progeny
      and remarkably, also in Cre transformants with multiple T-DNA copies. Therefore,
      a role is proposed for the CRE recombinase in preventing inverted T-DNA repeat
      formation or modifying the locus chromatin structure, resulting in a reduced
      sensitivity for silencing.

PMID- 19392708
TI  - Combined MRI-PET dissects dynamic changes in plant structures and functions.
AB  - Unravelling the factors determining the allocation of carbon to various plant
      organs is one of the great challenges of modern plant biology. Studying
      allocation under close to natural conditions requires non-invasive methods, which
      are now becoming available for measuring plants on a par with those developed for
      humans. By combining magnetic resonance imaging (MRI) and positron emission
      tomography (PET), we investigated three contrasting root/shoot systems growing in
      sand or soil, with respect to their structures, transport routes and the
      translocation dynamics of recently fixed photoassimilates labelled with the short
      lived radioactive carbon isotope (11)C. Storage organs of sugar beet (Beta
      vulgaris) and radish plants (Raphanus sativus) were assessed using MRI, providing
      images of the internal structures of the organs with high spatial resolution, and
      while species-specific transport sectoralities, properties of assimilate
      allocation and unloading characteristics were measured using PET. Growth and
      carbon allocation within complex root systems were monitored in maize plants (Zea
      mays), and the results may be used to identify factors affecting root growth in
      natural substrates or in competition with roots of other plants. MRI-PET co
      registration opens the door for non-invasive analysis of plant structures and
      transport processes that may change in response to genomic, developmental or
      environmental challenges. It is our aim to make the methods applicable for
      quantitative analyses of plant traits in phenotyping as well as in understanding
      the dynamics of key processes that are essential to plant performance.

PMID- 19392710
TI  - Coordination of cell proliferation and cell expansion mediated by ribosome
      related processes in the leaves of Arabidopsis thaliana.
AB  - Co-ordination of cell proliferation and cell expansion is a key regulatory
      process in leaf-size determination, but its molecular details are unknown. In
      Arabidopsis thaliana, mutations in a positive regulator of cell proliferation
      often trigger excessive cell enlargement post-mitotically in leaves. This
      phenomenon, called compensation syndrome, is seen in the mutant angustifolia3
      (an3), which is defective in a transcription co-activator. Such compensation,
      however, does not occur in response to a decrease in cell number in oligocellula
      (oli). oli2, oli5 and oli7 did not exhibit compensation and the reduction in cell
      number in these mutants was moderate. However, when an oli mutation was combined
      with a different oli mutation to create a double mutant, cell number was further
      reduced and compensation was induced. Similarly, weak suppression of AN3
      expression reduced cell number moderately but did not induce compensation
      compared with an an3 null mutant. Furthermore, double mutants of either oli2,
      oli5 or oli7 and an3 showed markedly enhanced compensation. These results suggest
      that compensation is triggered when cell proliferation regulated by
      OLI2/OLI5/OLI7 and AN3 is compromised in a threshold-dependent manner. OLI2
      encodes a Nop2 homolog in Saccharomyces cerevisiae that is involved in ribosome
      biogenesis, whereas OLI5 and OLI7 encode ribosome proteins RPL5A and RPL5B,
      respectively. This suggests that a factor involved in the induction of
      compensation may be under the dual control of AN3 and a ribosome-related process.

PMID- 19392709
TI  - Manipulation of plant innate immunity and gibberellin as factor of compatibility
      in the mutualistic association of barley roots with Piriformospora indica.
AB  - Fungi of the order Sebacinales (Basidiomycota) are involved in a wide spectrum of
      mutualistic symbioses with various plants, thereby exhibiting unique potential
      for biocontrol strategies. Piriformospora indica, a model organism of this fungal
      order, is able to increase the biomass and grain yield of crop plants, and
      induces local and systemic resistance to fungal diseases and tolerance to abiotic
      stress. To elucidate the molecular basis for root colonization, we characterized
      the interaction of P. indica with barley roots by combining global gene
      expression profiling, metabolic profiling, and genetic studies. At the metabolic
      level, we show that fungal colonization reduces the availability of free sugars
      and amino acids to the root tip. At the transcriptional level, consecutive
      interaction stages covering pre-penetration-associated events and progressing
      through to root colonization showed differential regulation of signal perception
      and transduction components, secondary metabolism, and genes associated with
      membrane transport. Moreover, we observed stage-specific up-regulation of genes
      involved in phytohormone metabolism, mainly encompassing gibberellin, auxin and
      abscisic acid, but salicylic acid-associated gene expression was suppressed. The
      changes in hormone homoeostasis were accompanied with a general suppression of
      the plant innate immune system. Further genetic studies showed reduced fungal
      colonization in mutants that are impaired in gibberellin synthesis as well as
      perception, and implicate gibberellin as a modulator of the root's basal defence.
      Our data further reveal the complexity of compatibility mechanisms in host
      microbe interactions, and identify gibberellin signaling as potential target for
      successful fungi.

PMID- 19392711
TI  - Herbivore metabolism and stoichiometry each constrain herbivory at different
      organizational scales across ecosystems.
AB  - Plant-herbivore interactions mediate the trophic structure of ecosystems. We use
      a comprehensive data set extracted from the literature to test the relative
      explanatory power of two contrasting bodies of ecological theory, the metabolic
      theory of ecology (MTE) and ecological stoichiometry (ES), for per-capita and
      population-level rates of herbivory across ecosystems. We found that ambient
      temperature and herbivore body size (MTE) as well as stoichiometric mismatch (ES)
      both constrained herbivory, but at different scales of biological organization.
      Herbivore body size, which varied over 11 orders of magnitude, was the primary
      factor explaining variation in per-capita rates of herbivory. Stoichiometric
      mismatch explained more variation in population-level herbivory rates and also in
      per-capita rates when we examined data from within functionally similar trophic
      groups (e.g. zooplankton). Thus, predictions from metabolic and stoichiometric
      theories offer complementary explanations for patterns of herbivory that operate
      at different scales of biological organization.

PMID- 19392712
TI  - Self-recognition affects plant communication and defense.
AB  - Animals have the ability to distinguish self from non-self, which has allowed
      them to evolve immune systems and, in some instances, to act preferentially
      towards individuals that are genetically identical or related. Self-recognition
      is less well known for plants, although recent work indicates that physically
      connected roots recognize self and reduce competitive interactions. Sagebrush
      uses volatile cues emitted by clipped branches of self or different neighbours to
      increase resistance to herbivory. Here, we show that plants that received
      volatile cues from genetically identical cuttings accumulated less natural damage
      than plants that received cues from non-self cuttings. Volatile communication is
      required to coordinate systemic processes such as induced resistance and plants
      respond more effectively to self than non-self cues. This self/non-self
      discrimination did not require physical contact and is a necessary first step
      towards possible kin recognition and kin selection.

PMID- 19392713
TI  - Immunological cost of chemical defence and the evolution of herbivore diet
      breadth.
AB  - Selective pressures from host plant chemistry and natural enemies may contribute
      independently to driving insect herbivores towards narrow diet breadths. We used
      the specialist caterpillar, Junonia coenia (Nymphalidae), which sequesters
      defensive compounds, iridoid glycosides, from its host plants to assess the
      effects of plant chemistry and sequestration on the larval immune response. A
      series of experiments using implanted glass beads to challenge immune function
      showed that larvae feeding on diets with high concentrations of iridoid
      glycosides are more likely to have their immune response compromised than those
      feeding on diets low in these compounds. These results indicate that larvae
      feeding on plants with high concentrations of toxins might be more poorly
      defended against parasitoids, while at the same time being better defended
      against predators, suggesting that predators and parasitoids can exert different
      selective pressures on the evolution of herbivore diet breadth.

PMID- 19392714
TI  - Geographical variation in predictors of mammalian extinction risk: big is bad,
      but only in the tropics.
AB  - Whereas previous studies have investigated correlates of extinction risk either
      at global or regional scales, our study explicitly models regional effects of
      anthropogenic threats and biological traits across the globe. Using phylogenetic
      comparative methods with a newly-updated supertree of 5020 extant mammals, we
      investigate the impact of species traits on extinction risk within each WWF
      ecoregion. Our analyses reveal strong geographical variation in the influence of
      traits on risk: notably, larger species are at higher risk only in tropical
      regions. We then relate these patterns to current and recent-historical human
      impacts across ecoregions using spatial modelling. The body-mass results
      apparently reflect historical declines of large species outside the tropics due
      to large-scale land conversion. Narrow-ranged and rare species tend to be at high
      risk in areas of high current human impacts. The interactions we describe between
      biological traits and anthropogenic threats increase understanding of the
      processes determining extinction risk.

PMID- 19392715
TI  - N:P stoichiometry and protein:RNA ratios in vascular plants: an evaluation of the
      growth-rate hypothesis.
AB  - The growth-rate hypothesis states that fast-growing organisms need relatively
      more phosphorus-rich RNA to support rapid rates of protein synthesis, and
      therefore predicts, within and among taxa, increases in RNA and phosphorus
      content (relative to protein and nitrogen content) with increased growth rate.
      Here, we present a test of this hypothesis in vascular plants. We determined
      nitrogen : phosphorus ratios and protein:RNA ratios in pines growing at different
      rates due to nutrient conditions. In general, when comparing leaves of the same
      species at low and high growth rates, the faster-growing plants had higher RNA
      content, higher %N and %P, and lower protein:RNA ratios, but not consistently
      lower N:P ratios. We found no link between growth rate and foliar N:P or
      protein:RNA when comparing multiple species of different inherent growth rates.
      We conclude that plants adjust the balance of protein and RNA to favour either
      speed or efficiency of protein synthesis, but this balance does not alone dictate
      leaf stoichiometry.

PMID- 19392716
TI  - History or ecology? Substrate type as a major driver of spatial genetic structure
      in Alpine plants.
AB  - Climatic history and ecology are considered the most important factors moulding
      the spatial pattern of genetic diversity. With the advent of molecular markers,
      species' historical fates have been widely explored. However, it has remained
      speculative what role ecological factors have played in shaping spatial genetic
      structures within species. With an unprecedented, dense large-scale sampling and
      genome-screening, we tested how ecological factors have influenced the spatial
      genetic structures in Alpine plants. Here, we show that species growing on
      similar substrate types, largely determined by the nature of bedrock, displayed
      highly congruent spatial genetic structures. As the heterogeneous and disjunctive
      distribution of bedrock types in the Alps, decisive for refugial survival during
      the ice ages, is temporally stable, concerted post-glacial migration routes
      emerged. Our multispecies study demonstrates the relevance of particular
      ecological factors in shaping genetic patterns, which should be considered when
      modelling species projective distributions under climate change scenarios.

PMID- 19392717
TI  - Changes in a tropical forest support metabolic zero-sum dynamics.
AB  - Major shifts in many ecosystem-level properties of tropical forests have been
      observed, but the processes driving these changes are poorly understood. The
      forest on Barro Colorado Island (BCI) exhibited a 20% decrease in the number of
      trees and a 10% increase in average diameter. Using a metabolism-based zero-sum
      framework, we show that increases in per capita resource use at BCI, caused by
      increased tree size and increased temperature, compensated for the observed
      declines in abundance. This trade-off between abundance and average resource use
      resulted in no net change in the rate resources are fluxed by the forest.
      Observed changes in the forest are not consistent with other hypotheses,
      including changes in overall resource availability and existing self-thinning
      models. The framework successfully predicts interrelated changes in size,
      abundance and temperature, indicating its utility for understanding changes in
      the structure and dynamics of ecosystems.

PMID- 19392718
TI  - Does elevated testosterone result in increased exposure and transmission of
      parasites?
AB  - Male-biased infection is a common phenomenon in vertebrate-parasite systems and
      male-biased transmission has been experimentally demonstrated. One mechanism that
      is hypothesized to create male-biased transmission is the immuno-suppressive
      effect of testosterone because it increases susceptibility to infection.
      Testosterone also influences host behaviour and, consequently, may increase
      exposure to parasites. To test how testosterone could increase exposure and
      transmission, we undertook a longitudinal mark-recapture study where we
      experimentally elevated testosterone levels in wild male rodents. Individuals in
      control populations reduced the average number of contacts over the treatment
      period, while populations with experimentally elevated testosterone levels
      maintained the number of contacts between hosts. As a result, the transmission
      potential was higher in testosterone treated populations compared to controls.
      Our results indicated that males with high-testosterone levels alter the
      population-level contacts, producing different social networks and increasing
      transmission potential compared to those where testosterone is at background
      levels.

PMID- 19392720
TI  - First WHO Global Consultation on Regulatory Requirements for Xenotransplantation
      Clinical Trials: Changsha, China, 19-21 November 2008. The Changsha Communique.

PMID- 19392719
TI  - Global consultation on regulatory requirements for xenotransplantation in
      clinical trials. Conference held in Changsha, China, November 19-21, 2008.

PMID- 19392721
TI  - Distribution and expression of porcine endogenous retroviruses in multi
      transgenic pigs generated for xenotransplantation.
AB  - BACKGROUND: Multi-transgenic pigs produced for use in xenotransplantation have to
      be screened for the presence and expression of porcine endogenous retroviruses
      (PERV) to select animals with low PERV load. The production of transgenic pigs
      may also be associated with the integration of the transgene adjacent to or into
      the locus of a PERV provirus, potentially leading to an enhanced virus
      expression. METHODS: Non-transgenic animals, single-transgenic, and multi
      transgenic pigs were screened for the presence of PERV-A, -B, and -C and
      recombinant PERV-A/C using polymerase chain reaction (PCR). PERV expression was
      determined by real time reverse transcriptase-PCR. An assay based on the
      activation of PERV in peripheral blood mononuclear cells by mitogens was used to
      discriminate between low and high PERV producer animals. RESULTS: All animals
      carried PERV-A and -B. A total of 176 from 181 (97.2%) animals carried PERV-C in
      the germ line and 18 from 64 animals carried PERV-A/C in the genome of lymphoid
      cells but not in the germ line. The expression of PERV was very low in all
      animals and not different between transgenic pigs and non-transgenic animals.
      PERV expression differed between various pig lines. The highest expression was
      found in mini-pigs and crossing other pig lines with mini-pigs resulted in
      increased PERV expression in the progeny. However, expression of viral proteins
      and particle release were not observed in all transgenic animals. CONCLUSIONS: No
      evidence for elevated PERV expression in (multi-) transgenic pigs was observed.
      Differences in PERV expression correlated with the genetic background of the
      animals, not with the specific transgene. Mini-pigs consistently had the highest
      level of PERV expression and animals with a mini-pig background had a higher
      level of expression compared with animals without mini-pig background.

PMID- 19392722
TI  - Acute cell-mediated rejection in orthotopic pig-to-mouse corneal
      xenotransplantation.
AB  - BACKGROUND: To investigate the role of T cells and natural killer (NK) cells in
      mediating corneal xenograft rejection in a pig-to-mouse model. METHODS: Pig
      corneas were orthotopically transplanted into BALB/c, C57BL/6, nude, severe
      combined immunodeficiency (SCID), and NOD/SCID/gammac(null) (NOG) mice. Graft
      survival was clinically assessed by slit-lamp biomicroscopy and median survival
      times (MST) were calculated. The rejected grafts were histologically evaluated
      using antibodies against CD4, CD8, NK1.1, and F4/80. RESULTS: The pig corneal
      xenografts were acutely rejected by BALB/c and C57BL/6 mice (MST 9.0 days), while
      nude, SCID and NOG mice rejected pig corneas in a more delayed fashion (MST 16.0,
      16.4, and 16.9 days, respectively). The majority of infiltrating cells found in
      rejected grafts in C57BL/6 mice were macrophages and CD4(+) T cells, while CD8(+)
      T cells and NK cells were rarely found. The grafts in nude mice had markedly
      decreased inflammatory infiltration with small numbers of macrophages and CD4(+)
      T cells. Infiltration was even more modest in grafts in SCID and NOG mice.
      CONCLUSIONS: T cells play an important role in acute rejection of pig corneal
      xenografts in mice, although acute rejection is not solely the result of T-cell
      mediated immunity. NK cells are less likely to be involved in the rejection
      process.

PMID- 19392723
TI  - Study of the microcirculation in hDAF transgenic rat livers xenoperfused with
      human blood.
AB  - BACKGROUND: The microcirculation was assessed in the livers of human decay
      accelerating factors (hDAF) and wild-type transgenic rats by fluorescent
      intravital microscopy, histology and histomorphology to determine the benefits of
      hDAF expression for the microcirculation of a rat liver xenograft perfused with
      human blood. METHODS: Male hDAF transgenic rats (group A; n = 20) and wild-type
      Sprague-Dawley rats (group B; n = 20) were xenoperfused with human blood, while
      other male wild-type Sprague-Dawley rats (group C; n = 10) were perfused with
      allogeneic blood. Following plasma and leukocyte staining with fluorescein
      sodium, and platelet staining with rhodamine, the right lobe of the liver was
      assessed by intravital microscopy, counting the numbers of perfused sinusoids and
      leukocytes adhering to the endothelium per mm(2), and calculating the acinar
      perfusion index (Pi). The liver underwent histological assessment at the end of
      each experiment. Mean +/- SEM values were calculated and the Mann-Whitney U-test
      was used for statistical analysis. RESULTS: The number of perfused sinusoids was
      higher in the group of hDAF rat livers (group A) and controls (group C) than in
      the group of non-transgenic rat livers perfused with human blood (group B) (P <
      0.05), although only group C still had a significantly more perfused sinusoids
      than the other groups after 90 min of perfusion (P < 0.05). The acinar perfusion
      index was higher in groups A and C than in group B (P < 0.05); here again, only
      group C still had a significantly higher Pi than group B after 90 min of
      perfusion (P < 0.05). There was a massive accumulation of leukocytes that peaked
      after 5 min and persisted throughout the perfusion in all three groups. Histology
      showed portal and subendothelial hepatic vein hemorrhage, necrosis and
      inflammatory reaction, which were particularly evident in group B. CONCLUSION: In
      our study, rat livers transgenic for hDAF were better protected against early
      tissue damage by perfusion with human blood, but this did not result in a longer
      xenograft survival.

PMID- 19392724
TI  - Pathogenesis of coxsackievirus-B5 acquired from intra-renal porcine islet cell
      xenografts in diabetic mice.
AB  - BACKGROUND: We previously demonstrated the ability of a human isolate of
      coxsackievirus-B5 (CVB5) to infect productively adult porcine islet cells (PICs)
      in vitro. PICs infected with CVB5 remain viable, and upon transplantation
      reversed diabetes in C56BL/6 mice for up to 5 days. METHODS: In the present work,
      we expanded this graft-to-host xenozoonosis model by examining the long-term
      functionality of CVB5-infected PIC xenografts in immunosuppressed mice. And, we
      characterized the pathogenesis of CVB5 infection in mice resulting from
      directional transmission of the virus from PIC xenografts to surrounding tissues
      in a mouse model for immunosuppressed human PIC xenograft recipients. RESULTS:
      Both acutely (12 h) and chronically (72 h) infected PIC xenografts functioned in
      vivo to reverse diabetes in mice. The efficacy of both infected and un-infected
      PICs was transient beyond 5 days post-inoculation and the long-term functionality
      of the grafts was compromised by host-to-graft rejection. CVB5-infected PIC
      xenografts transmitted infectious virus to immunosuppressed recipient mice
      resulting in extensive histopathologic changes. The virus replicated in the
      heart, liver, spleen, kidney, pancreas, brain and skeletal muscle in higher
      levels in severe-combined immunodeficient (SCID) mice that were directly
      inoculated with virus when compared to controls. In addition, infectious virus
      was recovered for up to 22 days after inoculation in SCID mice whereas it was
      only detected up to Day 4 PI in non-SCID mice. CONCLUSIONS: Immunosuppressed PIC
      xenograft recipients may be more susceptible to infection with CVB5 which could
      target the xenograft leading to disseminated infection in the host.

PMID- 19392725
TI  - In vitro and in vivo effects of the carbon monoxide-releasing molecule, CORM-3,
      in the xenogeneic pig-to-primate context.
AB  - BACKGROUND: Carbon monoxide (CO) interferes with inflammatory and apoptotic
      processes associated with ischemia-reperfusion injury and graft rejection. Here,
      the in vitro effects of carbon monoxide releasing molecule-3 (CORM-3), a novel
      water-soluble carbonyl CO carrier, have been investigated on porcine aortic
      endothelial cells (PAEC) and primate peripheral blood mononuclear cells (PBMC).
      Furthermore, the pharmacodynamics and pharmacotolerance of CORM-3 after
      administration of single and multiple doses in the primate have been assessed in
      view of its potential application in pig-to-primate xenotransplantation models.
      METHODS: For in vitro studies, PAEC and primate PBMC were exposed for 24, 48 and
      72 h to CORM-3 (20 to 1000 microm) and viability was measured using an MTS assay.
      PAEC and primate PBMC proliferation after exposure to CORM-3 was assessed by CFSE
      labelling. Proliferation of primate PBMC against irradiated pig lymphocytes was
      also assessed. Tumor necrosis factor alpha (TNF-alpha) production and Caspase-3
      and -7 activity in Concanavalin A (conA)-stimulated primate PBMC were measured
      following treatment with CORM-3. In vivo, CORM-3 was administered i.v. to
      cynomolgus monkeys at 4 mg/kg, as single or multiple doses for up to 30 days. The
      effect of CORM-3 was evaluated by the assessment of production of TNF-alpha and
      interleukin 1beta following PBMC stimulation with LPS by species-specific ELISA.
      Complete hematologic and biochemical analyses were routinely performed in treated
      primates. RESULTS: At concentrations <500 microm, CORM-3 did not alter the
      viability of PAEC or primate PBMC cultures in vitro, nor did it induce
      significant levels of apoptosis or necrosis. Interestingly, at concentrations of
      300 and 500 microm, significant PAEC proliferation was observed, whilst
      concentrations > or =50 microm inhibited conA-activated primate lymphocyte
      proliferation (IC(50) of 345.8 +/- 51.9 microm) and the primate xenogeneic
      response against pig PBMC. Such responses were demonstrated to be CO-dependent.
      In addition, CORM-3 significantly inhibited caspase-3 and -7 activity at
      concentrations between 200 and 500 microm and caused a significant reduction in
      TNF-alpha production (IC(50) 332.8 +/- 33.9 microm). In vivo, following the
      administration of multiple doses, TNF-alpha production was significantly reduced
      in comparison to pre-treatment responses, with decreased levels maintained
      throughout the study. Moreover, a slight and transient increase in transaminases
      and bilirubin was observed in animals exposed to multiple doses of CORM-3.
      CONCLUSIONS: These studies suggest that CORM-3 has anti-inflammatory and
      immunomodulatory properties in primates that may result in clinical benefit to
      allo- and xenografted organs.

PMID- 19392726
TI  - Xenotransplantation literature update January-February, 2009.

PMID- 19392727
TI  - Proptosis in a post-renal transplant patient with disseminated tuberculosis.
AB  - A 55-year-old male patient 13 years post living-related renal transplant on
      immunosuppressives presented with prolonged fever and a recent protrusion of the
      right eyeball. Evaluation revealed disseminated tuberculosis with a tuberculoma
      in the right orbit.

PMID- 19392728
TI  - The use of drotrecogin alfa (activated) in solid organ transplant patients: a
      case series.
AB  - BACKGROUND: Drotrecogin alfa (activated) (DAA), a recombinant human activated
      protein C, is indicated for the reduction of mortality in patients with severe
      sepsis who have a high risk of death. In the initial trial, DAA demonstrated a
      significant reduction in mortality at 28 days for patients treated with DAA in
      comparison with standard supportive treatment (placebo). However, solid organ
      transplant recipients were excluded from the study. Transplant recipients are at
      an increased risk for sepsis and there is minimal literature describing the
      safety and efficacy of DAA in the transplant population. METHODS: Thirteen solid
      organ transplant recipients who received DAA between November 2001 and January
      2004 were included in this case series. Patients were prospectively identified
      and data collection occurred concurrently and by retrospective chart review. All
      patients met the DAA use criteria based on the institutional standard protocol.
      RESULTS: We report the outcomes of the 13 adult transplant patients who received
      a total of 14 courses of DAA for severe sepsis. At the time of DAA initiation,
      all patients required mechanical ventilation, 86% necessitated vasopressor
      support, and had a median of 3 dysfunctional organs. The median Acute Physiology
      and Chronic Health Evaluation (APACHE) II score at initiation was 30. Overall,
      hemodynamic stability and APACHE II score improved at the end of DAA infusion.
      Causes of early discontinuation were bleeding (57%), scheduled procedure (14%),
      increased international normalized ratio (14%), and death (14%). In-hospital, 28
      day, and 1-year mortality was 69%, 62%, and 83%, respectively. CONCLUSION: DAA
      appears to be safe with appropriate monitoring. However, transplant recipients
      had a higher incidence of bleeding events leading to early discontinuation of
      DAA. Efficacy is difficult to assess without an appropriate control group for
      comparison.

PMID- 19392729
TI  - Safety and tolerability of cidofovir in high-risk pediatric patients.
AB  - Adenovirus (ADV) infection is a serious complication after hematopoietic stem
      cell transplantation with significant morbidity and mortality. Cidofovir has
      emerged as the primary therapy for ADV infection, but its use has been limited by
      concerns of nephrotoxicity. We report the safety and tolerability of 234
      cidofovir infusions in 23 patients at a single institution, and demonstrate
      evidence of acceptable nephrotoxicity despite concomitant use of other
      nephrotoxic agents. Three patients suffered adverse events, two related to the
      hydration regimen associated with cidofovir administration. We conclude that
      cidofovir is a safe and mostly well tolerated drug in a high-risk pediatric
      population.

PMID- 19392730
TI  - Pneumonia due to Legionella feeleii: case report and review of the literature.
AB  - Legionella feeleii is a rare cause of community-acquired pneumonia that occurs in
      immunocompromised hosts who are often receiving corticosteroid therapy. We report
      a 69-year-old man who underwent bone marrow transplantation and developed
      pneumonia due to L. feeleii, and review the clinical characteristics of 7 cases
      of L. feeleii infection reported in the literature.

PMID- 19392731
TI  - Nontuberculous mycobacterial infections after transplantation: a diversity of
      pathogens and clinical syndromes.

PMID- 19392732
TI  - Acute renal failure due to ureteral obstruction in a kidney transplant recipient
      with Candida albicans contamination of preservation fluid.
AB  - Reported rates of positive preservation fluid cultures range from 5% to 23%, with
      fungi accounting for 2-10% of all positive cultures. We report the case of a
      kidney transplant recipient who received a graft with preservation fluid
      contaminated by Candida albicans, who developed acute renal failure due to
      ureteral obstruction by fungus balls. The patient was treated with voriconazole
      with complete restoration of graft function. This rare clinical entity
      demonstrates the usefulness of pre-transplant cultures of preservation fluid, in
      order to identify a group of patients who could benefit from antifungal
      prophylaxis therapy and thereby prevent the need for graft nephrectomy.

PMID- 19392734
TI  - Abstracts of the ISPOR (International Society for Pharmacoeconomics and Outcomes
      Research) Fourteenth Annual International Meeting. May 16-20, 2009. Orlando,
      Florida, USA.

PMID- 19392733
TI  - Treatment of Strongyloides stercoralis hyperinfection-associated septic shock and
      acute respiratory distress syndrome with drotrecogin alfa (activated) in a renal
      transplant recipient.
AB  - We report a case of Strongyloides stercoralis hyperinfection syndrome in a renal
      transplant recipient complicated by septic shock, acute respiratory distress
      syndrome, and Klebsiella pneumoniae superinfection. The patient was treated
      successfully with drotrecogin alfa (activated), parenteral ivermectin,
      albendazole, and piperacillin/tazobactam. This outcome suggests that drotrecogin
      alfa (activated) may be useful therapy for transplant recipients who develop
      severe sepsis or septic shock secondary to potentially lethal opportunistic
      infections.

PMID- 19392736
TI  - Three global health reports: towards a growing consensus?

PMID- 19392737
TI  - Sensitivity and specificity of Chagas Stat-Pak test in Bolivia.
AB  - OBJECTIVE: To compare the results of an immunochromatographic test performed on
      whole blood, Chagas Stat-Pak, with those of an ELISA test using recombinant
      antigens. METHOD: We tested 995 subjects of a rural population of all ages in the
      south of Bolivia, 459 pregnant women of the same population and 1030 urban women
      giving birth from the east of Bolivia. RESULTS: The sensitivity of the CSP test
      for the entire studied population (n = 2484) was 94.73% [93.35-96.10]; the
      specificity was 97.33% [96.50-98.15]. However, the specificity differed
      significantly between rural pregnant and urban birthing women, which could be
      attributed either to differences of parasite strain or Chagas prevalence.
      CONCLUSION: The test is simple of use, reliable, relatively inexpensive (<2 US$
      each test) and its performances are compatible with a field use for large-scale
      screenings.

PMID- 19392738
TI  - Diagnostic performance and costs of Capilia TB for Mycobacterium tuberculosis
      complex identification from broth-based culture in Bangkok, Thailand.
AB  - OBJECTIVES: Broth-based culture (BBC) systems are increasingly being used to
      detect Mycobacterium tuberculosis complex (MTBC) in resource-limited. We
      evaluated the performance, time to detection and cost of the Capilia TB
      identification test from broth cultures positive for acid-fast bacilli (AFB) in
      Thailand. METHODS: From October-December 2007, broth cultures that grew AFB from
      specimens submitted by district TB clinics to the Bangkok city laboratory were
      tested for MTBC using Capilia TB and standard biochemical tests. Isolates that
      were identified as MTBC by biochemical tests but not by Capilia TB underwent
      repeat testing using Capilia TB, Accuprobe (Gen-Probe, San Diego, CA, USA) and
      sequencing. Costs of time, labour, infrastructure and consumables for all
      procedures were measured. RESULTS: Of 247 isolates evaluated, the sensitivity of
      Capilia TB was 97% and its true specificity 100% compared with biochemical
      testing. The median time from specimen receipt to confirmed MTBC identification
      was 20 days (range 7-53 days) for Capilia TB and 45 days (range 35-79 days) for
      biochemical testing (P < 0.01). Six isolates that were Capilia TB negative but
      positive by biochemical testing were confirmed as MTBC and mutations in the mpb64
      gene were detected in all. The unit cost of using Capilia TB was 2.67 USD that of
      biochemical testing was 8.78 USD. CONCLUSIONS: In Thailand, Capilia TB had
      acceptable sensitivity and specificity, was lower in cost and had shorter turn
      around times. Laboratories investing in BBC should consider Capilia TB for
      identification of MTBC, after validation of performance in their setting.

PMID- 19392739
TI  - Risk factors for typhoid in Darjeeling, West Bengal, India: evidence for
      practical action.
AB  - OBJECTIVE: To identify risk factors for typhoid and propose prevention measures.
      METHODS: Case-control study; we compared hospital-based typhoid cases defined as
      fever>38 degrees C for >or=3 days with four-fold rise in 'O' antibodies on paired
      sera (Widal) with community, age and neighbourhood matched controls. We obtained
      information on drinking water, fruits, vegetables, milk products and sanitation;
      and calculated matched odds ratios (MOR) and attributable fractions in the
      population (AFP) for the risk factors or failure to use prevention measures.
      RESULTS: The 123 typhoid cases (median age: 25 years, 47% female) and 123
      controls did not differ with respect to baseline characteristics. Cases were less
      likely to store drinking water in narrow-mouthed containers (MOR: 0.4, 95% CI:
      0.2-0.7, AFP 29%), tip containers to draw water (MOR: 0.4, 95% CI: 0.2-0.7, AFP
      33%) and have home latrines (MOR: 0.5, 95% CI: 0.3-0.8, AFP 23%). Cases were more
      likely to consume butter (OR: 2.3, 95% CI: 1.3-4.1, AFP 28%), yoghurt (OR: 2.3,
      95% CI: 1.4-3.7, AFP 34%) and raw fruits and vegetables, including onions (MOR:
      2.1, 95% CI: 1.2-3.9, AFP 34%), cabbages (OR: 2.8, 95% CI: 1.7-4.8, AFP 44%) and
      unwashed guavas (OR: 1.9, 95% CI: 1.2-3, AFP 25%). CONCLUSION: Typhoid was
      associated with unsafe water and sanitation practices as well as with consumption
      of milk products, fruits and vegetables. We propose to chlorinate drinking water
      at the point of use, wash/cook raw fruits and vegetables and ensure safer
      preparation/storage of local milk products.

PMID- 19392740
TI  - The epidemiology of malaria among pregnant women attending antenatal clinics in
      an area with intense and highly seasonal malaria transmission in northern Ghana.
AB  - OBJECTIVE: To describe the factors associated with malaria infection and anaemia
      in pregnancy in northern Ghana. METHOD: We studied 3642 pregnant women of all
      gravidities and gestational age of 18-32 weeks who attended an antenatal clinic
      in the Kassena-Nankana district of Ghana between June 2004 and July 2006. Blood
      samples were examined for haemoglobin concentrations and parasitaemia, and we
      obtained socio-demographic data, an obstetric history, information on their past
      and current state of health and bed net use. RESULTS: The overall prevalence of
      malaria parasitaemia during pregnancy was 47%. Older age [adjusted odds ratio
      (AOR) 0.65, 95% CI 0.54-0.78], multigravidity (AOR 0.51, 95% CI 0.42-0.61) and
      third trimester of pregnancy (AOR 0.85, 95% CI 0.73-0.99) were associated with a
      decreased risk of parasitaemia. Enrollment during the rainy or post-rainy season
      was associated with an increased risk of parasitaemia (AOR 2.59, 95% CI 2.20-3.04
      and AOR 3.12, 95% CI, 2.60-3.74 respectively). Malaria infection was associated
      with an increased risk of anaemia among young women. The prevalences of anaemia
      (Hb<11.0 g/dl) and severe anaemia (Hb<7.0 g/dl) during pregnancy were 72% and 2%
      respectively. The risk of anaemia was lower in older women (AOR 0.79, 95% CI,
      0.64-0.97), multigravidae (AOR 0.67, 95% CI 0.55-0.83) and in educated women (AOR
      0.81, 0.68-0.98). CONCLUSION: The prevalence of malaria parasitaemia and anaemia
      among pregnant women in Kassena-Nankana district is high with marked seasonal
      variation. Targeting of interventions to the high transmission season and to
      paucigravidae may be appropriate in this setting.

PMID- 19392741
TI  - The poorest of the poor: a poverty appraisal of households affected by visceral
      leishmaniasis in Bihar, India.
AB  - OBJECTIVE: To provide data about wealth distribution in visceral leishmaniasis
      (VL)-affected communities compared to that of the general population of Bihar
      State, India. METHODS: After extensive disease risk mapping, 16 clusters with
      high VL transmission were selected in Bihar. An exhaustive census of all
      households in the clusters was conducted and socio-economic household
      characteristics were documented by questionnaire. Data on the general Bihar
      population taken from the National Family Health Survey of India were used for
      comparison. An asset index was developed based on Principal Components Analysis
      and the distribution of this asset index for the VL communities was compared with
      that of the general population of Bihar. RESULTS: 83% of households in
      communities with high VL attack rates belonged to the two lowest quintiles of the
      Bihar wealth distribution. All socio-economic indicators showed significantly
      lower wealth for those households. CONCLUSION: Visceral leishmaniasis clearly
      affects the poorest of the poor in India. They are most vulnerable, as this
      vector-born disease is linked to poor housing and unhealthy habitats. The disease
      leads the affected households to more destitution because of its impact on
      household income and wealth. Support for the present VL elimination initiative is
      important in the fight against poverty.

PMID- 19392742
TI  - The female sex work typology in India in the context of HIV/AIDS.
AB  - OBJECTIVE: To conduct a critical review of the typology of female sex work in
      India. METHOD: Published and unpublished studies (1986-2008) were identified
      through electronic databases, hand searching and contacting experts. RESULTS: The
      review assesses the appropriateness of the existing typologies from a
      programmatic perspective and identifies their strengths and limitations. It
      indicates there is conceptual confusion around the typology and that none of the
      existing typologies are exhaustive, in that none includes all types of sex work
      documented in India. The typology developed by the National AIDS Control
      Organization (NACO) is the most comprehensive. The typology is based on the
      primary place of solicitation and categorizes female sex workers (FSWs) as
      brothel-based, street-based, home-based, lodge-based, dhaba-based and highway
      based FSWs. However, this typology has its limitations. First, it does not
      include all categories of FSWs documented in the literature, such as indirect
      primary (primarily solicit clients at their places of work, which are venues
      where facilitating sex work is their main purpose e.g. massage parlours, bars),
      indirect-secondary (primarily solicit clients at their places of work, which are
      in non-sex work related industries e.g. agriculture, construction) and phone
      based FSWs (primarily solicit clients through phones). Second, the methodology
      used to develop the typology proposed by NACO or by any other researchers is not
      explicit. In addition, the extent to which the typology captures the HIV risk
      variability between FSWs types is not explored. CONCLUSION: There is a need to
      develop an evidence-based, inclusive typology which takes account of HIV risk for
      researchers and programmers.

PMID- 19392743
TI  - Turning points, reproduction number, and impact of climatological events for
      multi-wave dengue outbreaks.
AB  - OBJECTIVES: To study climatological and public health events which might have
      affected the 2007 two-wave dengue outbreak in Taiwan, an island with both
      tropical and subtropical regions, where the 2007 dengue incidence exceeded the
      combined total of the previous four years. METHODS: A multi-phase Richards model
      was fitted to weekly cumulative dengue data to pinpoint the turning points of the
      outbreak. We obtained the 'initial' reproduction numbers for the two waves of the
      outbreak. By means of correlation analysis we explored the possible impact of
      climatological events on the occurrence of turning points. RESULTS: Three turning
      points occurred around early August, late August/early September, and late
      October/early November. The 'initial' reproduction number for the first wave was
      R(i) = 4.67 (95% CI: 0*-10.92), where 0* = max{0, lower bound}, and R(i) = 3.93
      (95% CI: 1.74-6.13) for the second wave. The highest correlation was between
      dengue incidence and two climatological variables: maximum temperature at a lag
      of 5 weeks (r = 0.66 and 0.71) and total precipitation at a lag of seven weeks (r
      = 0.53). Conclusions The first two turning points were partially attributable to
      two typhoons around early to mid-August that brought a sharp drop in temperature
      and substantial rainfall. The drop in temperature first drove the dengue
      incidence down, then the rainfall drove it up at the beginning of fall. In recent
      years, Taiwan has witnessed increasingly frequent large summer dengue outbreaks
      that persisted into early winter, perhaps due to warmer autumns. This highlights
      the possible impact of global warming on the spread of infectious diseases.

PMID- 19392744
TI  - Progress towards the Millennium Development Goals in a community of extreme
      poverty: local vs. national disparities in Peru.
AB  - OBJECTIVES: Standard indicators are being used worldwide to track progress
      towards achieving the Millennium Development Goals (MDGs). These are usually at
      country level and do not accurately reflect within-country variability of
      progress towards the targets. This may lead to lack of attention and under
      resourcing of the most vulnerable populations. Therefore, the objective of this
      study was to compare selected standard MDG indicators at country level and
      community level in Peru. METHODS: As MDG indicators we selected: (i) moderate to
      severe and severe underweight in children under 5 years old; (ii) immunization
      against measles in 1-year olds; (iii) births attended by skilled health
      professionals and (iv) youth unemployment. Country-level data for Peru were
      obtained from United Nations published sources. Community-level data were
      obtained from a household survey conducted in 2005-2006 in Belen, a community of
      extreme poverty in the Amazon region. RESULTS: Belen indicators were consistently
      less favourable than country-level indicators, and indicators even differed
      between zones of high and low socioeconomic status within Belen itself.
      CONCLUSIONS: Compared to MDG indicators at the national level in Peru, the
      population of Belen experiences intra-country regional disparities in important
      health and social outcomes. Improving the coverage and quality of interventions
      and services in this community is essential. Other vulnerable populations in Peru
      should also be identified and targeted so that they can benefit from, and
      ultimately contribute to, progress in achieving the MDGs.

PMID- 19392745
TI  - Simple and inexpensive point-of-care tests improve diagnosis of vaginal
      infections in resource constrained settings.
AB  - OBJECTIVE: Bacterial vaginosis (BV) and Trichomonas vaginalis infection (TV) have
      been associated with adverse birth outcomes and increased risk for HIV. We
      compare the performance of simple inexpensive point-of-care (POC) tests to
      laboratory diagnosis and syndromic management of BV and TV in poor settings.
      METHODS: Between November 2005 and March 2006, 898 sexually active women
      attending two reproductive health clinics in Mysore, India were recruited into a
      cohort study investigating the relationship between vaginal flora and HSV-2
      infection. Participants were interviewed and screened for reproductive tract
      infections. Laboratory tests included serology for HSV-2; cultures for TV,
      Candida sp., and Neisseria gonorrhoeae; Gram stains; and two POC tests: vaginal
      pH; and Whiff test. RESULTS: Of the 898 participants, 411 [45.7%, 95% confidence
      interval (95% CI): 42.4-49.0%] had any laboratory diagnosed vaginal infection. BV
      was detected in 165 women (19.1%, 95%CI: 16.5-21.9%) using Nugent score. TV was
      detected in 76 women (8.5%, 95%CI: 6.7-10.4%) using culture. Among the entire
      study population, POC correctly detected 82% of laboratory diagnosed BV cases,
      and 83% of laboratory diagnosed TV infections. Among women with complaints of
      vulval itching, burning, abnormal vaginal discharge, and/or sores (445/898), POC
      correctly detected 83% (60 of 72 cases) of laboratory diagnosed BV cases vs. 40%
      (29 of 72 cases) correctly managed using the syndromic approach (P < 0.001).
      Similarly, POC would have detected 82% (37 of 45 cases) of TV cases vs. 51% (23
      of 45 cases) correctly managed using the syndromic approach (P = 0.001).
      CONCLUSIONS: In the absence of laboratory diagnostics, POC is not only
      inexpensive and practical, but also significantly more sensitive than the
      syndromic management approach, resulting in less overtreatment. .

PMID- 19392746
TI  - Association between socio economic status and schistosomiasis infection in Jinja
      District, Uganda.
AB  - OBJECTIVE: To examine the role of socioeconomic situation in influencing the risk
      and intensity of infection with Schistosomiasis mansoni. METHODS: Cross-sectional
      study in Walukuba Division bordering Lake Victoria, Jinja District. We assessed a
      random sample of 463 individuals aged 10-20 years for Schistosoma mansoni
      infection, water contact behaviour and treatment status with praziquantel as of
      the last mass treatment. Socioeconomic conditions of the participants' households
      were assessed by calculating a wealth index (based on type of housing and
      ownership of assets). Households were classified in four classes; multivariate
      logistic regression analysis was used to identify independent predictors of being
      infected with schistosomiasis. Intensities of infection with S. mansoni were
      compared across the classes of wealth index. RESULTS: Wealth index emerged a risk
      factor for infection with S. mansoni after controlling for water contact and
      treatment with praziquantel. The adjusted odds ratio of being infected for the
      lowest level of wealth index compared to the highest was 10.42 (95% CI 3.38-32.36
      P < 0.001). The intensity of infection decreased with wealth index Linearity F
      ratio 13.91, 1 df, P < 0.001). The geometric egg count for those in the lowest
      wealth index was 230 (95% CI 199-279) compared to 114 (95% CI 80-162) for the
      highest wealth index. CONCLUSIONS: In addition to mass treatment with
      praziquantel, improving the socio-economic conditions of the population should be
      given priority.

PMID- 19392747
TI  - Barriers to TB care for rural-to-urban migrant TB patients in Shanghai: a
      qualitative study.
AB  - OBJECTIVE: To understand barriers to tuberculosis (TB) care among migrant TB
      patients in Shanghai after the introduction of the TB-free treatment policy which
      has applied to migrants since 2003, and to provide policy recommendations to
      improve TB control in migrant populations in big cities. METHODS: In-depth
      interviews were conducted with 34 migrant patients who registered on the Shanghai
      TB programme as new bacteria positive pulmonary TB cases. Patients were
      purposively selected across six districts of Shanghai to give a balance of gender
      and TB treatment phase. RESULTS: Financial constraints were reported as the
      biggest barriers to TB service among migrant patients. Many migrant patients
      experienced high medical costs both before and after their TB diagnosis. The
      government free treatment policy only covered a small fraction of patients' total
      costs. However, respondents tended to stay in Shanghai for treatment because
      their families were in Shanghai, they were more confident with the quality of
      medical care there or they felt they could not earn cash at home. Migrant
      patients had a limited knowledge of TB and the free TB treatment policy, and
      reported being laid off from work or avoided after having TB. CONCLUSIONS: Health
      system problems caused the biggest barrier to migrant patients' access to TB
      care. The free treatment policy alone has little, if any, effect in reducing
      migrant patients' financial stress: it is also essential to provide social
      welfare, including living subsidies, for poor migrant TB patients.

PMID- 19392748
TI  - A package of primary health care services for comprehensive family-centred
      HIV/AIDS care and treatment programs in low-income settings.
AB  - Particularly in resource-limited settings, HIV/AIDS is a family concern. Separate
      services for children and adults may make accessing care more difficult for
      families than services where family members can be cared for together. Implicit
      in comprehensive, family-centred approaches to care are the broader notions of
      longitudinal primary care and linkages to other services, including those based
      in communities. As highly-active antiretroviral therapy becomes more available,
      and the direct burden of HIV-associated morbidity diminishes, HIV-infected
      individuals require primary care that goes beyond exclusive management of HIV and
      related conditions, including preventive services and the management of common
      medical issues. The prevention of tuberculosis, diarrhoea, and, in endemic
      regions, malaria; the addressing of debilitating depression; cervical screening;
      and the management of chronic cardiovascular disease and its risk factors are all
      of benefit to patients accessing HIV/AIDS care. Packaging such services is an
      effective means both of standardizing care within a program and of ensuring
      patients receives a full roster of available interventions. As family-centred
      care models develop in resource-limited settings, the availability of evidence
      based service packages such as presented here will help program designers
      prioritize available human and materiel resources toward those interventions that
      improve patients' global health and well being.

PMID- 19392749
TI  - A guide for better understanding between patients and doctors.

PMID- 19392751
TI  - Cytologic examination of fine-needle aspirates from mammary gland tumors in the
      dog: diagnostic accuracy with comparison to histopathology and association with
      postoperative outcome.
AB  - BACKGROUND: Mammary tumors are the most common neoplasms in female dogs.
      Malignant tumors may carry a poor prognosis and necessitate surgery. Few data are
      available on the value of cytologic examination as a diagnostic or prognostic
      tool for mammary tumors in dogs. OBJECTIVES: The objectives of this study were to
      determine whether cytologic findings in fine-needle aspirate specimens of canine
      mammary tumors correlate with histopathologic results and whether the cytologic
      diagnosis is associated with postoperative outcome. METHODS: In this prospective
      study, fine-needle aspirate samples were obtained from 50 mammary tumors in 50
      dogs. Results of cytologic and histopathologic examination were compared, using
      the histologic diagnosis as the reference method. Kaplan-Meier log rank analysis
      was used to evaluate univariate association of the cytologic diagnosis with
      duration of survival, local control, and metastasis-free interval. RESULTS:
      Adequate cytologic samples were obtained in 43/50 (86%) cases. The cytologic
      diagnosis correlated with the histologic diagnosis for benign and malignant
      tumors in 40/43 (93%) and 35/43 (81%) cases, respectively. Cytologic examination
      had a sensitivity of 88% and a specificity of 96% for the diagnosis of
      malignancy. The cytologic diagnosis had significant univariate association with
      duration of survival (P=.016), recurrence-free interval (P=.003), and metastasis
      free interval (P=.014). CONCLUSIONS: Cytologic examination of mammary tumors in
      the dog has satisfactory accuracy, sensitivity, and specificity for the diagnosis
      of malignancy and is associated with postoperative outcome. Further studies on
      the diagnostic accuracy of cytology as well as multivariate analysis of its
      preoperative prognostic value in mammary tumors in the dog are warranted.

PMID- 19392752
TI  - What is your diagnosis? Ascites fluid from an 11-year-old dog with epigastric
      bulging.
AB  - An 11-year-old, intact female, Yorkshire Terrier dog was presented with
      epigastric bulging. Results of a CBC included mild neutrophilia and
      thrombocytopenia. Radiographic examination and abdominal ultrasonography revealed
      abundant ascites and a well-circumscribed mass in the caudal region of the
      spleen. Abdominocentesis revealed bloody fluid. Cytologic analysis of the fluid
      revealed numerous clustered and individual large cells with moderate anisocytosis
      and anisokaryosis. The spleen was surgically resected. An imprint smear of a
      white nodular tumor on the caudal pole of the spleen contained a bimorphic
      population of small and large lymphocytes. The cytologic diagnosis was lymphoma.
      Histologically, large lymphocytes with distinct borders and single nucleoli
      formed multiple neoplastic follicles. The final diagnosis was primary splenic
      lymphoma. Immunocytochemical staining results on buffy coat smears prepared from
      the ascites fluid showed the lymphocytes were negative for CD3 and positive for
      CD79a, indicating B-cell origin. Further investigation of the cell clusters using
      semiquantitative reverse transcriptase-PCR showed that ICAM-1, a cell-cell
      adhesion molecule, was overexpressed in the tumor cells, likely contributing to
      the clustering of neoplastic lymphocytes in the ascites fluid. Usually, round
      cells are not adherent; however, spontaneously detached round cells may form
      clusters, as in this case, and must be differentiated from epithelial tumors.

PMID- 19392753
TI  - Analysis and cytologic characterization of hemocytes from freshwater mussels
      (Quadrula sp.).
AB  - BACKGROUND: Freshwater mussels are among the most endangered taxa in North
      America and minimally invasive techniques to evaluate their health are needed.
      OBJECTIVE: The objective of this study was to develop a standardized approach for
      identifying and enumerating the cellular components of freshwater mussel
      hemolymph. METHODS: Hemocyte clumping, total hemocyte count, and hemocyte
      morphology were compared in untreated hemolymph or hemolymph treated with
      formalin, sodium citrate, sodium heparin, EDTA, water, or l-cysteine. Morphology
      was then used to categorize hemocytes and perform a 100-cell differential.
      RESULTS: Treatment with formalin or >25 mg/mL l-cysteine reduced hemocyte
      clumping, although only formalin significantly increased the total hemocyte
      count. However, formalin also induced crenation that impaired hemocyte
      identification. Both EDTA and sodium citrate-induced hemocyte degranulation while
      sodium citrate and >40 mg/mL l-cysteine-induced cell lysis. Hemocytes could be
      categorized into 2 groups of granulocytes (eosinophilic or basophilic) and 2
      groups of agranulocytes (large or small) for performing a cytologic differential.
      The differential was not significantly altered by anticoagulant treatments
      providing cell morphology was adequate for obtaining a differential. Eosinophilic
      granulocytes predominated (59%) with fewer large agranulocytes (27%) and
      basophilic granulocytes (13%). Small agranulocytes comprised 2% of the total
      population. CONCLUSIONS: No single treatment provided an optimal method to
      evaluate freshwater mussel hemolymph. Maximal hemocyte counts were obtained
      following formalin treatment. l-cysteine reduced clumping and maintained hemocyte
      morphology for performing a cytologic differential. These techniques provide a
      standardized approach for the hematologic evaluation of freshwater mussels.

PMID- 19392754
TI  - C-reactive protein concentration in dogs with primary immune-mediated hemolytic
      anemia.
AB  - BACKGROUND: Canine primary immune-mediated hemolytic anemia (IMHA) is associated
      with a high-mortality rate. C-reactive protein (CRP) is the most important acute
      phase protein in dogs and may have value as a marker of prognosis or response to
      treatment in IMHA. OBJECTIVE: The objectives of this study were to evaluate serum
      CRP concentration in dogs with primary IMHA at presentation and during treatment,
      to assess potential differences based on survival time, and to compare CRP with
      other laboratory parameters of inflammation and prognosis. METHODS: Inclusion
      criteria for primary IMHA were anemia (PCV<0.30 L/L), a positive Coombs' test or
      persistent autoagglutination of erythrocytes, and the exclusion of underlying
      diseases by other diagnostic tests. Dogs were divided into 2 groups based on
      survival: dogs that were still alive 14 days after start of treatment (group 1)
      and dogs that died or were euthanized before day 14 (group 2). Serum CRP
      concentration, a CBC, and a biochemistry profile were performed on days 0, 3, 8,
      and 14. Serum CRP also was determined in 25 clinically healthy dogs. RESULTS: CRP
      concentration in the 25 clinically healthy dogs ranged from 0-8.9 microg/mL
      (median 2.2 microg/mL). Thirty dogs were diagnosed with primary IMHA, 24 in group
      1 and 6 in group 2. On day 0, CRP concentration in dogs in both groups (median
      224 microg/mL) was increased above the reference interval. In group 1 dogs,
      median CRP concentration was 242 microg/mL on day 0, 69 microg/mL on day 3, 35
      microg/mL on day 8, and 2 microg/mL on day 14. In group 2 dogs, median CRP
      concentration was 194 microg/mL on day 0, 119 microg/mL on day 3, and 41
      microg/mL on day 8; only 1 dog in group 2 survived to day 8. There was a
      significant correlation between CRP and total WBC concentrations on days 0 and 3
      (r=-.598, P=.003). CONCLUSIONS: Serum CRP concentration was markedly increased in
      dogs with primary IMHA. CRP concentration did not differ based on patient
      survival, but might be a marker for long-term monitoring of these patients.

PMID- 19392755
TI  - Unusual "erythroid loops" in canine blood smears after viper-bite envenomation.
AB  - Northern Italy is a habitat for many species of viper; Vipera aspis is
      responsible for most reported bites of humans and animals. Five dogs of different
      breeds and ages were presented by their owners to a veterinary clinic in northern
      Italy between September 2004 and August 2007 with a history of being bitten by a
      viper within the past 2 hours. On physical examination, all of the dogs were
      depressed, had pale mucous membranes, and had a painful area consistent with a
      recent viper bite wound on the nose (2), distal front leg (2), or lip (1).
      Hemoglobinemia and hemoglobinuria were observed in plasma and urine from all
      dogs. CBCs were done at the time of presentation, daily for 4 days, and 10 days
      after presentation in all dogs with the exception of one dog that died after 2
      days. All dogs had an acute decrease in HCT within 24 hours of presentation; all
      dogs had neutrophilia, 3/5 had a mildly toxic left shift, and 4/5 had
      thrombocytopenia. On Diff-Quik-stained blood smears, moderate numbers of
      echinocytes, spherocytes, and erythrocyte ghosts were observed. In addition,
      moderate numbers of unusual erythrocyte membrane-like structures ("erythroid
      loops") were observed. The loops were annular in shape and sometimes disrupted,
      appearing as thin pale blue bands. Erythrocyte morphologic abnormalities
      decreased by day 3 and were no longer observed on day 10. The unique appearance
      of the erythroid loops together with evidence for intravascular hemolysis and
      other erythrocyte morphologic changes suggest they may be a consequence of
      erythrocyte lysis. Echinocytes, spherocytes, and erythrocyte ghosts are known to
      result from the action of phospholipase in viper venom; however, erythroid loops
      have not been reported previously and their exact mechanism of formation is
      unknown.

PMID- 19392756
TI  - Evaluation of serum haptoglobin and C-reactive protein in dogs with mammary
      tumors.
AB  - BACKGROUND: In veterinary medicine, there is increasing interest in measuring
      acute phase proteins as a tool in the diagnosis and monitoring of neoplastic
      diseases. Although mammary neoplasms are the most common type of cancer in dogs,
      acute phase proteins have not been extensively evaluated in dogs with mammary
      tumors. OBJECTIVES: The aim of this study was to evaluate serum haptoglobin (Hp)
      and C-reactive protein (CRP) concentrations in the dogs with mammary tumors and
      assess their potential association with malignancy. METHODS: A retrospective
      study of dogs with mammary tumors was performed. Serum concentrations of CRP and
      Hp were determined in healthy control dogs (n=20) and dogs with mammary tumors
      before surgery (n=41). Mammary tumors were grouped as carcinomas (n=24),
      fibrosarcoma (n=1), malignant mixed tumors (n=7), benign mixed tumors (n=6), and
      adenomas (n=3). CRP and Hp concentrations were compared in dogs with different
      tumor types and were also compared based on tumor size, lymph node infiltration,
      skin ulceration, fixation to underlying tissue, and time between tumor
      identification and removal. RESULTS: Hp concentration was significantly (P<.043)
      higher in dogs with mammary tumors (median 2.03 g/L, range 0.09-2.94 g/L)
      compared with controls (1.38 g/L, range 0.08-3.00 g/L), but the range of values
      overlapped considerably. CRP concentration was higher in dogs with carcinomas
      (4.70 mg/L, range 0.63-128.96 mg/L) vs controls (2.11 mg/L, range 0.25-6.57 mg/L)
      (P=.0008) and in dogs with ulcerated skin (14.8 mg/L, range 5.7-128.9 mg/L, n=3)
      compared with those without ulceration (2.4 mg/L, range 0.11-30.3 mg/L, n=38)
      (P=.048). CONCLUSIONS: Serum Hp and CRP do not appear to have value in diagnosing
      or predicting malignancy of mammary tumors in dogs. Higher CRP concentrations in
      dogs with mammary carcinoma suggest a role for inflammation in this tumor type.

PMID- 19392757
TI  - Comparison between manual and automated total nucleated cell counts using the
      ADVIA 120 for pleural and peritoneal fluid samples from dogs, cats, horses, and
      alpacas.
AB  - BACKGROUND: Analysis of body fluids includes an estimate of total nucleated cell
      count (TNCC). Automated methods may enhance the accuracy and timeliness of TNCC
      results. OBJECTIVE: The purpose of this report was to assess the ability of the
      ADVIA 120 hematology analyzer to accurately count nucleated cells in pleural and
      peritoneal fluids from animals, compared with manual counts. METHODS: Pleural and
      peritoneal fluids submitted in EDTA tubes to our laboratory over a 17-month
      period were used in the study. TNCC/microL was determined by a manual method,
      using a hemocytometer, and by an automated method, using the ADVIA 120.
      Correlation of results was determined by Passing-Bablok regression, Bland-Altman
      plots, and Pearson correlation analysis. RESULTS: Samples from dogs (n=36), cats
      (n=36), horses (n=59), and alpacas (n=11) were analyzed. High correlation in TNCC
      between methods was found for peritoneal fluid (n=93, r=.959), pleural fluid
      (n=49, r=.966), and all fluids combined (n=142, r=.960) (P<.001). Variation
      between methods was greater in samples with TNCCs<1000/microL (r=.62, P<.001).
      The ADVIA systematically overestimated the number of cells in all fluid samples
      by 95 cells/microL (confidence interval=19.2-190.5/muL). CONCLUSION: The ADVIA
      120 reliably determines TNCC in pleural and peritoneal effusions and can be
      recommended for routine veterinary laboratory analysis.

PMID- 19392758
TI  - Capillary electrophoresis for the detection of bilirubin in rat serum.
AB  - BACKGROUND: The rat is used often to assess the toxicity of new chemical entities
      in preclinical drug development. Bilirubin concentration in rat serum is
      routinely determined by colorimetric methods, but false positive results due to
      hemolyzed serum or direct interferences by test compounds may occur. Capillary
      electrophoresis (CE) is an automated method that requires small sample volume and
      facilitates the direct detection of bilirubin. OBJECTIVE: The purpose of this
      study was to evaluate a CE method for detecting bilirubin and albumin-bound
      bilirubin in rat serum and to measure potential interference by hemolysis and
      specific test compounds. METHODS: Serum samples from male Sprague Dawley rats
      (n=20) were used in the study. Results obtained on a Beckman P/ACE MDQ CE
      instrument equipped with a UV-detector were compared with those obtained using a
      colorimetric method on a Hitachi 912 analyzer. Bilirubin standards were used to
      evaluate the detection and stability of bilirubin in rat serum, and vials with
      ultrafiltration membranes were used to separate albumin-bound bilirubin. Intraday
      and interday coefficients of variation (CV), linearity, and the effects of added
      hemoglobin and a test compound on CE results were determined. RESULTS: The CE
      method was capable of detecting bilirubin and albumin-bound bilirubin in rat
      serum samples with reproducible results and good accuracy. CVs were <3% and
      linearity of the CE assay was high (R(2)=0.9951). Abnormally high bilirubin peaks
      due to the presence of hemoglobin or the test compound were easily distinguished
      by means of CE. CONCLUSION: CE is a good alternative to the colorimetric methods
      currently used for the determination of bilirubin in rat serum.

PMID- 19392759
TI  - Evaluation of platelet function in dogs with cardiac disease using the PFA-100
      platelet function analyzer.
AB  - BACKGROUND: Cardiac disease has the potential to alter platelet function in dogs.
      Evaluation of platelet function using the PFA-100 analyzer in dogs of multiple
      breeds and with a broad range of cardiac conditions would help clarify the effect
      of cardiac disease on platelets. OBJECTIVES: The objective of this study was to
      assess differences in closure time (CT) in dogs with cardiac disease associated
      with murmurs, when compared with that of healthy dogs. METHODS: Thirty-nine dogs
      with cardiac murmurs and turbulent blood flow as determined echocardiographically
      were included in the study. The dogs represented 23 different breeds. Dogs with
      murmurs were further divided into those with atrioventricular valvular
      insufficiency (n=23) and subaortic stenosis (n=9). Fifty-eight clinically healthy
      dogs were used as controls. CTs were determined in duplicate on a PFA-100
      analyzer using collagen/ADP cartridges. RESULTS: Compared with CTs in the control
      group (mean+/-SD, 57.6+/-5.9 seconds; median, 56.5 seconds; reference interval,
      48.0-77.0 seconds), dogs with valvular insufficiency (mean+/-SD, 81.9+/-26.3
      seconds; median, 78.0 seconds; range, 52.5-187 seconds), subaortic stenosis
      (71.4+/-16.5 seconds; median, 66.0 seconds; range, 51.5-95.0 seconds), and all
      dogs with murmurs combined (79.6+/-24.1 seconds; median, 74.0 seconds; range,
      48.0-187 seconds) had significantly prolonged CTs (P<.01). CONCLUSIONS: The PFA
      100 analyzer is useful in detecting platelet function defects in dogs with
      cardiac murmurs, most notably those caused by mitral and/or tricuspid valvular
      insufficiency or subaortic stenosis. The form of turbulent blood flow does not
      appear to be an important factor in platelet hypofunction in these forms of
      cardiac disease.

PMID- 19392760
TI  - Adipokines: a review of biological and analytical principles and an update in
      dogs, cats, and horses.
AB  - In addition to its role as an energy storage depot, adipose tissue is now
      recognized as a complex endocrine organ. Adipose tissue releases a variety of
      factors, termed adipokines, that regulate energy metabolism, cardiovascular
      function, reproductive status, and immune function. Some of the better-studied
      adipokines include leptin, adiponectin, and components of the renin-angiotensin
      system such as angiotensinogen. The function of more recently discovered
      adipokines such as resistin are under intense scrutiny. Abnormal production or
      regulation of adipokines occurs in obese individuals and is implicated in the
      development of a variety of associated co-morbidities including metabolic
      syndrome, type 2 diabetes, atherosclerosis, heart disease, and cancer in people,
      although evaluation in domestic species is just beginning. Adipokines are now
      being examined as potential biomarkers for risk assessment for development of
      complications related to obesity. This article summarizes the function and
      regulation of some better-characterized adipokines. It also reviews the current
      information on the characterization of adipokines in some domestic species in
      which rates of obesity and obesity-related disorders are increasing, such as the
      dog, cat, and horse.

PMID- 19392761
TI  - Cytologic interpretation of canine cerebrospinal fluid samples with low total
      nucleated cell concentration, with and without blood contamination.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) is potentially altered by iatrogenic blood
      contamination at the time of sampling due to the addition of blood-associated
      leukocytes and protein. OBJECTIVES: The objective of this study was to assess
      whether protein concentration, neutrophil percentage, and the presence of
      activated macrophages, reactive lymphocytes, or eosinophils in CSF samples with
      low total nucleated cell concentration (TNCC) are affected by blood contamination
      or associated with central nervous system (CNS) disease. METHODS: Case records
      from the Royal Veterinary College Diagnostic Laboratory were searched
      retrospectively for dogs with CSF having < or =5 TNCC/microL. TNCC, RBC, and
      protein concentrations; neutrophil percentage; and the presence of activated
      macrophages, reactive lymphocytes, and eosinophils were recorded. Results of
      magnetic resonance imaging (MRI) also were recorded as a marker of CNS disease.
      RESULTS: Of 906 cases evaluated, 106 (12%) had blood contamination (>500
      RBCs/microL) in CSF. Protein concentration and neutrophil percentage were
      significantly higher and the presence of eosinophils was more likely in blood
      contaminated vs noncontaminated samples. Non-blood-contaminated samples with
      activated macrophages or reactive lymphocytes had higher protein concentrations
      and neutrophil percentages, and those with activated macrophages were more likely
      to have a positive finding on MRI. CONCLUSIONS: Protein concentration, neutrophil
      percentage, and the presence of eosinophils are significantly affected by blood
      contamination in canine CSF having low TNCC. Activated macrophages and reactive
      lymphocytes are not affected by blood contamination, however, and may be useful
      in identifying dogs with CNS abnormalities.

PMID- 19392762
TI  - Validation of the Sysmex XT-2000iV hematology system for dogs, cats, and horses.
      II. Differential leukocyte counts.
AB  - BACKGROUND: The Sysmex XT-2000iV is a laser-based, flow cytometric hematology
      system that stains nucleic acids in leukocytes with a fluorescent dye. A 4-part
      differential is obtained using side fluorescence light and laser side scatter.
      OBJECTIVE: The purpose of this study was to validate the Sysmex XT-2000iV for
      determining differential leukocyte counts in blood from ill dogs, cats, and
      horses. METHODS: Blood samples from diseased animals (133 dogs, 65 cats, and 73
      horses) were analyzed with the Sysmex XT-2000iV (Auto-diff) and the CELL-DYN
      3500. Manual differentials were obtained by counting 100 leukocytes in Wright
      stained blood smears. RESULTS: Leukocyte populations in the Sysmex DIFF
      scattergram were usually well separated in equine samples, but were not as well
      separated in canine and feline samples. Correlation among the Sysmex XT-2000iV,
      CELL-DYN 3500, and manual counts was excellent for neutrophil counts (r >or=.97)
      and good for lymphocyte counts (r >or=.87) for all three species. Systematic
      differences between the 3 methods were seen for lymphocyte and monocyte counts.
      The Sysmex reported incomplete differential counts on 18% of feline, 13% of
      canine, and 3% of equine samples, often when a marked left shift (>10% bands)
      and/or toxic neutrophils were present. Eosinophils were readily identified in
      cytograms from all 3 species. Neither the Sysmex nor the CELL-DYN detected
      basophils in the 7 dogs and 5 cats with basophilia. CONCLUSIONS: The Sysmex XT
      2000iV automated differential leukocyte count performed well with most samples
      from diseased dogs, cats, and horses. Basophils were not detected. Immature
      neutrophils or prominent toxic changes often induced errors in samples from cats
      and dogs.

PMID- 19392763
TI  - Validation of the Sysmex XT-2000iV hematology system for dogs, cats, and horses.
      I. Erythrocytes, platelets, and total leukocyte counts.
AB  - BACKGROUND: The Sysmex XT-2000iV is a laser-based, flow cytometric hematology
      system that has been introduced for use in large and referral veterinary
      laboratories. OBJECTIVE: The purpose of this study was to validate the Sysmex XT
      2000iV for counting erythrocytes, reticulocytes, platelets, and total leukocytes
      in blood from ill dogs, cats, and horses. METHODS: Blood samples from diseased
      animals (133 dogs, 65 cats, and 73 horses) were analyzed with the Sysmex XT
      2000iV and the CELL-DYN 3500. Manual reticulocyte counts were done on an
      additional 98 canine and 14 feline samples and manual platelet counts were done
      on an additional 73 feline and 55 canine samples, and compared with automated
      Sysmex results. RESULTS: Hemoglobin concentration, RBC counts, and total WBC
      counts on the Sysmex were highly correlated with those from the CELL-DYN
      (r>/=0.98). Systematic differences occurred for MCV and HCT. MCHC was poorly
      correlated in all species (r=0.33-0.67). The Sysmex impedance platelet count in
      dogs was highly correlated with both the impedance count from the CELL-DYN
      (r=0.99) and the optical platelet count from the Sysmex (r=0.98). The Sysmex
      optical platelet count included large platelets, such that in samples from cats,
      the results agreed better with manual platelet counts than with impedance
      platelet counts on the Sysmex. Canine reticulocyte counts on the Sysmex
      correlated well (r=0.90) with manual reticulocyte counts. Feline reticulocyte
      counts on the Sysmex correlated well with aggregate (r=0.86) but not punctate
      (r=0.50) reticulocyte counts. CONCLUSION: The Sysmex XT-2000iV performed as well
      as the CELL-DYN on blood samples from dogs, cats, and horses with a variety of
      hematologic abnormalities. In addition, the Sysmex detected large platelets and
      provided accurate reticulocyte counts.

PMID- 19392764
TI  - What is your diagnosis? Marked hyperchloremia in a dog.
AB  - A 5-year-old neutered male Cavalier King Charles Spaniel was evaluated for a 3
      week history of progressive paresis. The dog had been receiving potassium citrate
      capsules to acidify urine for the past 2 years because of an earlier history of
      urolithiasis. Results of neurologic examination, spinal cord radiography, and
      magnetic resonance imaging of the skull and spinal cord revealed no lesions that
      could have accounted for the neurologic signs. The main abnormalities on a
      clinical chemistry profile were marked hyperchloremia (179 mmol/L, reference
      interval 108-122 mmol/L) and an anion gap of -50.4 mmol/L (reference interval
      16.3-28.6 mmol/L). Because of the severe hyperchloremia, serum bromide
      concentration was measured (400 mg/dL; toxic concentration >150 mg/dL; some dogs
      may tolerate up to 300 mg/dL). Analysis of the potassium citrate capsules, which
      had been compounded at a local pharmacy, yielded a mean bromide concentration of
      239 mg/capsule. Administration of the capsules was discontinued and there was
      rapid resolution of the dog's neurologic signs. This case of extreme bromide
      toxicity, which apparently resulted from inadvertent use of bromide instead of
      citrate at the pharmacy, illustrates the importance of knowing common
      interferents with analyte methodologies and of pursing logical additional
      diagnostic tests based on clinical and laboratory evidence, even when a patient's
      history appears to rule out a potential etiology.

PMID- 19392765
TI  - What is your diagnosis? Hemorrhagic effusion in a dog.
AB  - A 2-year-old spayed female, German Shepherd dog was presented to the University
      of Illinois Veterinary Teaching Hospital with a history of intermittent lethargy.
      On physical examination, lung sounds were increased. The dog had a mild fever
      (103.7 degrees F) and mild tachycardia (120 bpm). Thoracic ultrasound revealed a
      sternal mass and pericardial effusion, both of which were aspirated. On cytologic
      examination, the pericardial fluid contained a large amount of blood and was
      interpreted as a hemorrhagic effusion. Nucleated cells consisted mainly of
      macrophages containing phagocytized RBCs and hemosiderin and many clusters of
      reactive mesothelial cells. The majority of mesothelial cells contained variable
      amounts of rod-shaped brown pigment granules that were suspected to be iron. The
      granules were positive for Prussian blue and carbol-fuschin, indicative of iron
      potentially mixed with lipofuscin. The granules stained negatively with Melan A,
      rhodamine, Hall's, and periodic acid-Schiff. The iron within the mesothelial
      cells was likely secondary to hemorrhage, based on the erythrophagia and
      accumulation of hemosiderin in macrophages. Iron deposition and phagocytic
      activity in mesothelial cells has been reported previously in humans and rats,
      but not in dogs.

PMID- 19392766
TI  - Canine nodular dermatophytosis (kerion): 23 cases.
AB  - Dermatophytosis is a common zoonotic disease, and one of its clinical
      presentations in the dog is nodular dermatophytosis (kerion). Because the
      infection is located within the dermis, routine diagnostic tests such as a Wood's
      lamp examination, microscopic examination of hair shafts for fungal elements and
      fungal culture can yield negative results. In such cases, histopathological
      examination with routine and special stains (periodic acid-Schiff, Gomori
      methenamine silver) is required to confirm the diagnosis. Nodular dermatophytosis
      in 23 dogs of different breed, age and sex with single or multiple nodules is
      described. Twelve dogs had a single nodule, and 11 dogs showed multiple lesions.
      Wood's lamp examination was negative in all cases. Microscopic examination of
      plucked hairs showed arthrospores in 8 of 23 cases. Skin scrapings in mineral oil
      looking for arthrospores and/or hyphae were positive in 12 cases. Impression
      smears of exudates were diagnostic in 21 of 23 cases (91%), showing arthrospores
      within fragments of hair shafts or free among neutrophils and macrophages
      (pyogranulomatous inflammation). Histopathology was performed in two cases.
      Fungal culture was positive for Microsporum canis in 16 dogs and for Microsporum
      gypseum in one dog. In six cases, the causative agent was not identified by
      fungal culture. All dogs were treated with systemic antifungal therapy and in
      eight cases with concurrent antibiotic therapy. Nodular dermatophytosis resolved
      in all dogs with the prescribed treatments within 4 to 8 weeks. Transmission to
      people or other pets in the home was not found.

PMID- 19392767
TI  - Extracutaneous neutrophilic inflammation in a dog with lesions resembling Sweet's
      Syndrome.
AB  - A 7-year-old-spayed female standard poodle dog presented to the Iowa State
      University Veterinary Teaching Hospital with an 8-day history of lethargy, left
      hind limb lameness, ptyalism and peripheral lymphadenomegaly. On physical
      examination, the dog was lethargic, febrile (40.5 degrees C) and had multifocal
      to coalescing erythematous papular to pustular eruptions on the skin of all four
      limbs, periocularly and on the ventral and lateral thorax and abdomen.
      Histopathological findings from skin biopsies of the papules revealed a severe
      diffuse neutrophilic dermatitis with sub- and intra-epithelial pustules. Four
      days after being admitted the dog died from cardiac and respiratory failure. At
      necropsy, in addition to the multifocal to coalescing erythematous papules, the
      skin contained scattered pustules. Additionally, the subcutaneous tissue
      surrounding the right stifle was diffusely oedematous, and the peripheral and
      visceral lymph nodes were enlarged. The predominant histologic lesion was
      neutrophilic inflammation, in the absence of detectable bacteria in the skin,
      heart, lungs, oesophagus and left tarsus. In the absence of neoplasia or
      bacteraemia, a syndrome similar to Sweet's Syndrome should be considered as a
      differential diagnosis in dogs with cutaneous and extracutaneous neutrophilic
      infiltrates.

PMID- 19392768
TI  - Staphylococcal colonization of mucosal and lesional skin sites in atopic and
      healthy dogs.
AB  - Staphylococcal colonization was compared in healthy dogs and in dogs with atopic
      dermatitis. Bacterial swabs were collected from the nasal mucosa, ear and
      perineum of 43 healthy and 24 atopic dogs and also from potentially infected skin
      lesions of the atopic dogs. Coagulase positive staphylococcal isolates were
      identified to the species level. At the time of this study Staphylococcus
      intermedius was considered a single species but has since been recognized as
      comprising at least three species with canine isolates believed to belong to
      Staphylococcus pseudintermedius. Of atopic dogs, 87.5% were colonized with S.
      intermedius compared to only 37.2% of healthy dogs. The ear was the only carriage
      site that showed any significant difference in S. intermedius isolation between
      healthy and atopic dogs. The perineum represented the most frequently colonized
      mucosal site for both groups. Sampling the nasal mucosa alone identified 71.4% of
      atopic and 37.5% of healthy S. intermedius carriers. Inclusion of a perineal swab
      identified 100% of atopic and 93.8% of healthy carriers. S. intermedius was
      isolated from all the lesional sites sampled from atopic dogs. Significantly
      fewer dogs were colonized by Staphylococcus aureus than S. intermedius, and there
      was no significant difference between S. aureus colonization of atopic and
      healthy dogs. S. aureus was not recovered from any lesions in atopic dogs. The
      results show that S. intermedius carriage is more prevalent in atopic dogs
      compared to healthy dogs and that to identify staphylococcal carriers both the
      nasal mucosa and the perineum should be sampled.

PMID- 19392769
TI  - Research opportunities for pathogen reduction/inactivation of blood components:
      summary of an NHLBI workshop.
AB  - In July 2008, a workshop sponsored by the Division of Blood Diseases and
      Resources of the National Heart, Lung, and Blood Institute (NHLBI) was convened
      to identify potential research opportunities that could advance our understanding
      of both the biologic and the clinical impact of the various available pathogen
      reduction/inactivation (PR/PI) methods of blood components (platelets [PLTs], red
      blood cells, and plasma) intended for allogeneic transfusion. These discussions
      resulted in consensus that, even though several PR/PI technologies have already
      been licensed and are being used in Europe and elsewhere for PLTs and plasma,
      concerns about possible side effects, particularly component quality and
      pulmonary toxicity, have impeded regulatory approval in North America (United
      States and Canada). Such concerns thus threaten to stall further development of
      these technologies. As a consequence, the NHLBI workshop participants focused on
      formulating a series of research-related recommendations to better understand,
      mitigate, and prevent these adverse effects. Other important issues identified
      included the need for a single method to inactivate pathogens in whole blood
      without damaging the various blood components; new ways to monitor the efficacy
      of treated components, including animal models to screen for safety; a better
      understanding of the effect of PR/PI-treated products on recipient
      alloimmunization, tolerance, and immune modulation; understanding the impact of
      PR/PI on various other noninfectious hazards of transfusion; and establishing
      methods to evaluate risk-benefit and cost-effectiveness, in particular with
      reference to emerging pathogens. The working group also discussed issues related
      to specific blood components, such as improving the process of clinical
      evaluation, investigating the impact of PR/PI on component storage lesions,
      understanding mechanisms that reduce component viability, and addressing the
      underlying resistance to the adoption of PR/PI-treated components. This
      communication summarizes the opinions of workshop participants on these issues
      and concludes with a list of areas for possible research that could advance the
      application of PR/PI methods to enhance the safety of the world's blood supplies.

PMID- 19392770
TI  - One-year experience of nucleic acid technology testing for human immunodeficiency
      virus Type 1, hepatitis C virus, and hepatitis B virus in Thai blood donations.
AB  - BACKGROUND: Blood donations collected at the National Blood Center, the Thai Red
      Cross Society, Bangkok, in 2007 were tested by nucleic acid amplification
      technology (NAT) using the Chiron TIGRIS/Procleix Ultrio test and the Roche cobas
      s 201/cobas TaqScreen multiplex (MPX) test. STUDY DESIGN AND METHODS: The
      sensitivity, specificity, and robustness were determined by testing 486,676
      seronegative blood donations. Samples from each day of collection were divided
      into two sets; the odd-numbered samples were tested individually on the TIGRIS
      and the even-numbered samples were tested in pools of 6 on the cobas s 201. The
      status of reactive samples was confirmed by duplicate testing of samples from the
      plasma bag to calculate the test specificity. Reactive samples were tested on the
      alternate system and followed up. RESULTS: The analytical sensitivity of both
      systems met the 95% limits of detection claimed by the respective package
      inserts. No cross contamination was seen with either system. Test specificity was
      99.93 and 99.90% for the Procleix Ultrio and cobas TaqScreen tests, respectively.
      The NAT yield rates for human immunodeficiency virus Type 1 (HIV-1), hepatitis C
      virus (HCV), and hepatitis B virus (HBV) were 1:97,000, 1:490,000, and 1:2800,
      respectively. Several occult HBV donors, the majority of whom were detected by
      both tests, were also identified. The HIV-1 and HCV window cases were detected
      with both tests. CONCLUSION: The performances of the systems and tests indicated
      that both were acceptable for routine NAT by the National Blood Center, the Thai
      Red Cross Society. However, the Procleix Ultrio test appeared to be less
      sensitive than the cobas TaqScreen test for HBV.

PMID- 19392772
TI  - In vitro platelet function of platelet concentrates prepared using  three
      different apheresis devices determined by impedance and  optical aggregometry.
AB  - BACKGROUND: Septic transfusion reactions to apheresis platelets (PLTs) continue
      to occur despite preventive measures. This study evaluated the effect of two
      operational changes designed to reduce bacterial risk: 1) introducing inlet-line
      sample diversion on two-arm procedures and 2) increasing the sample volume
      cultured from 4 to 8 mL from all donations. STUDY DESIGN AND METHODS: Aerobic
      culture results and septic transfusion reactions reported between December 1,
      2006, and July 31, 2008 (Period 2), were compared to March 1, 2004, to May 31,
      2006 (Period 1). RESULTS: During Period 2, a total of 781,936 apheresis PLT
      collections were cultured, of which 130 donations (1:6015) were confirmed
      positive and 9 (1:86,882) had negative culture results but were associated with
      11 septic reactions. Confirmed-positive cultures from two-arm procedures
      decreased (27.2 to 14.7 per 105 collections; odds ratio [OR], 0.54; 95%
      confidence interval [CI], 0.41-0.70) in Period 2, owing to a lower rate of skin
      flora contamination. Detection of contamination of one-arm collections
      significantly increased by 54% in Period 2 (13.7 vs. 21.1 per 105 collections;
      OR, 1.54; 95% CI, 1.05-2.27). Fewer septic transfusion reactions occurred in
      Period 2, but the difference did not reach significance (1.7 vs. 1.2 per 105
      donations; OR, 0.68; 95% CI, 0.30-1.53). CONCLUSION: Inlet-line diversion
      decreased bacterial contamination during two-arm collections by more than 46%.
      Concurrently, doubling the sample volume was associated with a 54% relative
      increase in culture sensitivity. These interventions act cooperatively to
      decrease bacterial risk.

PMID- 19392771
TI  - Elevated Ca2+ influx-inducing activity toward mast cells in pretransfusion sera
      from patients who developed transfusion-related adverse reactions.
AB  - BACKGROUND: Type I allergic reactions such as urticaria-like manifestations
      constitute a large percentage of transfusion-related adverse events. Along with
      donor factors, patient factors might be involved in these reactions. Sera from
      some patients with chronic idiopathic urticaria show histamine-releasing activity
      (HRA). Sera from patients who develop Type I allergic reaction might possess HRA.
      STUDY DESIGN AND METHODS: Pretransfusion serum samples were collected. Mast cells
      were cultured from peripheral blood CD34+ cells and mixed with the serum samples.
      Cells with elevated intracytoplasmic Ca2+ concentrations were monitored using
      flow cytometry to evaluate Ca2+ influx-inducing activity (CaIA) in serum. The
      amount of histamine released into the supernatant was measured using an enzyme
      immunoassay kit to evaluate HRA. In some assays, cells were incubated with
      pertussis toxin (Ptx). RESULTS: CaIA values were higher (p < 0.05) in sera from
      patients with reactions (27.68 +/- 20.38 [n = 145]; range, 0.49-84.90) than in
      sera of patients without reactions (10.70 +/- 6.50 [n = 54]; range, 2.67-36.97)
      and control sera (9.67 +/- 5.88 [n = 107]; range, 1.11-25.68). No difference in
      CaIA was found between patients with (27.38 +/- 20.46 [n = 88]) and without
      (28.38 +/- 20.59 [n = 57]) skin manifestations. However, CaIA was higher (p <
      0.05) in patients with pure urticaria (mean, 30.58 +/- 21.3 [n = 30]; range,
      70.43-4.1) than in patients with fever alone (mean, 18.61 +/- 14.71 [n = 18];
      range, 45.94-3.19). Levels of HRA were higher (p < 0.001) in CaIA-positive sera
      than in CaIA-negative sera. Both CaIA and HRA were blocked by Ptx. CONCLUSION:
      Elevated CaIA and HRA in pretransfusion sera might be attributable to adverse
      reactions, especially to urticaria-like manifestation. The Gi protein-coupled
      receptor complexes on mast cells and its ligand must be involved.

PMID- 19392773
TI  - Immunophenotypical, morphologic, and functional characterization of maturation
      associated plasmacytoid dendritic cell subsets in normal adult human bone marrow.
AB  - BACKGROUND: Information about maturation of plasmacytoid dendritic cell
      precursors (pre-pDCs) in normal bone marrow (BM) remains limited. STUDY DESIGN
      AND METHODS: Immunophenotypical, morphologic, and functional changes associated
      with maturation of pre-pDCs were analyzed in adult normal human BM (n = 45).
      RESULTS: Three pre-pDC maturation stages, with an increasingly higher degree of
      maturity, were systematically identified: CD34++/HLA-DR++/+++/CD123++/CD45+/++
      (Stage I), CD34+/HLA-DR+/++/CD123++/+++/CD45+/++ (Stage II), and CD34-/HLA
      DR++/CD123++/+++/CD45++ (Stage III) cells. Lymphoid- and early myeloid-associated
      molecules, as well as CD86, were coexpressed in Stage I pre-pDCs, being down
      regulated afterward. CD304 and CD85j appeared in Stage I, progressively
      increasing their levels thereafter. Interestingly, cutaneous lymphocyte
      associated antigen was heterogeneously expressed throughout the maturation,
      particularly in Stage I pre-pDCs. The morphologic appearance of Stage I pre-pDCs
      was consistent with their undifferentiated stage, while Stage II/III cells showed
      morphologic features of more differentiated cells. From the functional point of
      view, only Stage II and Stage III pre-pDCs were capable of inducing allogeneic T
      cell proliferation, the later subset also showing interferon-g secretion; in
      contrast, Stage I pre-pDCs showed the highest endocytic ability. CONCLUSION: In
      summary, three maturation stages of pre-pDCs can be identified in adult normal
      BM, which show unique phenotypical, morphologic, and functional characteristics;
      these results provide a frame of reference for a better understanding of pDC
      malignancies.

PMID- 19392774
TI  - Retrospective analysis of autologous blood use in bimaxillary repositioning
      osteotomy surgery: a quality improvement study.
AB  - BACKGROUND: Multiple studies have considered the necessity of preoperative
      autologous blood donation before bimaxillary orthognathic osteotomies. In the
      context of a quality improvement project, this topic was also investigated in our
      institution. Furthermore, the transfusion practice was analyzed and the
      correlations between patient, operative variables, and blood loss were studied.
      STUDY DESIGN AND METHODS: In accordance with the recommendations of the Federal
      Medical Association and the Federal Ministry for Health and Social Security, a
      transfusion demand list was compiled using data of 82 patients who underwent
      bimaxillary orthognathic surgery between 1997 and 2005. The maximum blood loss
      tolerable without transfusion (MBL) was calculated for each patient on the basis
      of sex, weight, height, and preoperative hematocrit (Hct). This was compared with
      the actual transfusion and blood loss data. RESULTS: An autologous blood donation
      was carried out in 65 of 82 patients (79.3%). Sixty-two of 65 autologous blood
      donors (95.4%) and 2 of 17 patients (11.8%) without autologous blood donation
      received transfusion. The actual blood loss did not exceed the calculated MBL in
      48 of the 82 cases. Nevertheless, 31 of these 48 patients (64.6%) received
      transfusions. For patients with a low calculated MBL, only a trend to a higher
      transfusion rate was observed, although the actual blood loss in these cases more
      often exceeded the individually calculated MBL (p < 0.01). In addition,
      transfusion triggers (Hct 0.22 or hemoglobin 7.5 g/dL) were also more often seen
      in cases with low calculated MBL (p < 0.05). CONCLUSIONS: In this study, an
      inappropriate transfusion practice in patients undergoing bimaxillary
      orthognathic osteotomies after preoperative autologous blood donation was
      detected. Calculation of the individual MBL should be used to help identify
      patients at high risk for transfusion and guide adequate methods to decrease the
      need of homologous blood.

PMID- 19392775
TI  - Extracellular DNA in cord blood plasma and applications in cord blood banking for
      sample identification.
AB  - BACKGROUND: Human cord blood (CB) units donated for transplantation require
      testing for various markers in blood and plasma aliquots. Although the identity
      link between the CB unit and the labeled aliquots with the same identifiers can
      be confirmed by HLA-DNA assays, these methods have not been used for CB plasma.
      We have previously reported that viral DNA sequences are present in the CB plasma
      of carrier babies and now hypothesize that human genomic DNA may also be present
      in CB plasma. STUDY DESIGN AND METHODS: The aim of the study was to determine
      whether human genomic DNA is also present in CB plasma in quality and quantity
      able to support human genetic identification by short tandem repeat analysis
      (STR). RESULTS: The presence of extracellular DNA (EC-DNA) in CB and adult
      peripheral blood plasma was confirmed by HLA-DR polymerase chain reaction (PCR)
      and real-time PCR of Alu (SB2) genes. High concentrations were seen in CB plasma
      (0.131 ng/mL vs. adult 0.005 ng/mL; p < 0.001). EC-DNA increased over time while
      CB was stored at room temperature; this increase was associated with decreasing
      cell viability. STR-PCR of EC-DNA showed good signal strength and accurate allele
      calling so that linkage between the infant donor, the collected CB unit, and CB
      plasma aliquots could be established. CONCLUSION: This study demonstrates that
      infant-derived EC-DNA is present in CB plasma and provides a useful tool for the
      unambiguous confirmation of plasma aliquot identity, as routinely used in CB
      banking, by the use of a sensitive and highly accurate DNA assay.

PMID- 19392776
TI  - Molecular bases of unexpressed RHD alleles in Chinese D- persons.
AB  - BACKGROUND: The aim of this study was to use a systematic survey to analyze RHD
      alleles in Chinese D- donors who do not express D antigen or who lack functional
      RhD protein. STUDY DESIGN AND METHODS: A total of 733 D-Chinese donors, not
      including Del phenotypes, were investigated by RHD polymorphism-specific
      polymerase chain reaction (PCR), Rhesus box PCR-PstI digestion, and RHD
      sequencing. The frequencies of identified alleles were calculated. RESULTS: Three
      genetic mechanisms and eight alleles were found associated with the Chinese D-
      phenotype. One new RHD/CE hybrid allele and one novel mutation were also found.
      The rates of total deletion and the most frequent hybrid allele RHD(1)-CE(2-9)
      D(10) were similar to those found in previous studies. A previously reported
      mutation RHD(711delC) was found to be the predominant cause of aberrant RHD
      alleles. CONCLUSION: Informative population-based data for improving molecular
      diagnostic strategies for Chinese D- persons are suggested by this study. This
      type of systematic knowledge is important for the development of typing and
      transfusion strategies for the Chinese population.

PMID- 19392777
TI  - Long-term cryopreservation of autologous stem cell grafts: a clinical and
      experimental study of hematopoietic and immunocompetent cells.
AB  - BACKGROUND: Autologous stem cell transplantation(ASCT) is used in the treatment
      of several malignancies.Harvesting sufficient peripheral blood progenitor cells
      (PBPCs) for a potential second autotransplantation at the time of relapse several
      years after diagnosis is becoming an increasingly common practice. STUDY DESIGN
      AND METHODS: Cryopreserved PBPCs were prepared with different concentrations of
      dimethyl sulfoxide (DMSO; 2, 4, 5, and 10%) and stored for at least 5 years
      before the recovery of CD34+ cells and various T- and natural killer (NK)-cell
      subsets were analyzed by flow cytometry. Furthermore,clinical variables for
      myeloma patients having a second autotransplantation with long-term-stored
      autografts were evaluated. RESULTS: The number of viable CD34+ cells in longterm
      stored grafts was higher when autografts were cryopreserved with 4 or 5% than
      with 2 and 10%DMSO. The number of viable CD34+ cells was reduced by 13.9% after 5
      years of cryostorage in 5% DMSO.Lymphocyte viability was also higher with 4 or
      5%DMSO. However, the frequencies of several T-cell subsets showed DMSO-dependent
      differences,whereas NK-cell subsets did not. Furthermore, after a second
      autotransplantation with long-term-stored PBPC grafts at the time of myeloma
      relapse (median storage time, 42 months) all 17 patients reached neutrophil
      counts exceeding 0.5 x 109/L and platelet counts exceeding 20 x 109/L within 15
      days. There was no difference in engraftment between patients receiving
      autografts preserved with 5 and 10% DMSO. CONCLUSION: PBPC autografts can safely
      be stored for at least 5 years in 5% DMSO and used for ASCT.

PMID- 19392778
TI  - What type of information is trusted by whom? A multilevel analysis of the
      stability of the information source-trust association for blood transfusion.
AB  - BACKGROUND: It has been suggested that transfusion information from scientific
      sources (vs. popular sources) is seen as more trustworthy and that interventions
      should consider using scientific styles. Before such suggestions can be
      implemented, it is necessary to know if this science source-trust link is
      observed across different sociodemographic groups and psychological
      characteristics. A large-scale field-based study examining the importance of
      sociodemographics and psychological characteristics on the source-trust link was
      conducted. STUDY DESIGN AND METHODS: A large field-based experiment (the Euro
      Blood Substitutes Project) was conducted on four different samples (the general
      public, blood donors, patients, and health experts) in the UK and The Netherlands
      (total n = 3935). Questions examined levels of trust about sources of transfusion
      medicine, various aspects of knowledge, and demographic data. RESULTS: People
      differentiated between scientific and popular sources, with scientific sources
      perceived as more trustworthy. General trust in transfusion medicine was higher
      for those who believe that they or scientists were knowledgeable about
      transfusion medicine or genetic modification (GM). This suggests that people do
      not differentiate in their subjective knowledge between GM and transfusion
      medicine. This science trust-source relationship was moderated by a variety of
      demographic (e.g., younger people were more likely to trust scientific sources)
      and psychological (e.g., those who rate science as knowledgeable were more
      trusting of scientific sources) factors. CONCLUSION: The trust-source link is not
      stable and communications should be targeted to the specific population samples
      for which they will be most effective; scientifically styled information will be
      particularly effective for communicating information within certain populations.

PMID- 19392779
TI  - New cellular therapies: is there a role for transfusion services?

PMID- 19392780
TI  - Not every PRP-gel is born equal. Evaluation of growth factor availability for
      tissues through four PRP-gel preparations: Fibrinet, RegenPRP-Kit, Plateltex and
      one manual procedure.
AB  - BACKGROUND: The rationale for using topical platelet gel therapy is to provide
      the healing tissues with concentrated platelet-derived factors. Several systems
      are available to prepare platelet-rich plasma (PRP) and from these, the platelet
      gel. These systems produce two- to six-fold platelet and growth factor-enriched
      concentrations. The bioavailability of growth factors in tissue healing depends
      on the amount of growth factors stored in platelets but a portion of these is
      lost during platelet manipulation. Very few data have been reported on the
      kinetics of growth factor release from PRP-gels. The aim of this study is to
      assess the growth factor recovery and its bioavailability to tissues in four
      different PRP and PRP-gel preparation techniques. MATERIALS AND METHODS: Three
      commercially available devices (Fibrinet, RegenPRP-Kit, Plateltex) and one manual
      procedure (home made, HM) were evaluated with reference to resulting platelet
      concentration, growth factor content and the kinetics of growth factor release
      from gel. RESULTS: Platelet concentration increased from 1.65- to 4.4-fold in
      comparison with whole blood initially used. The final platelet concentration (x
      10(3)/microl) was: Fibrinet 1358 +/- 419, Regen 430 +/- 109, HM 1196 +/- 188, and
      Plateltex 1160 +/- 164. A high variation (5- to 27-fold) was found in growth
      factor concentration in relation to the method used and also a high variation in
      the kinetics of growth factor release from gels. CONCLUSIONS: Similar methods for
      platelet gel preparation revealed different performances concerning growth factor
      recovery and the kinetics of its release from the gel. It is unclear whether
      these noticeable differences are important for clinical management.

PMID- 19392781
TI  - Use of the haematopoietic progenitor cell parameter in optimizing timing of
      peripheral blood stem cell harvest.
AB  - BACKGROUND AND OBJECTIVES: Timing of peripheral blood stem cell (PBSC) harvest is
      typically based on quantification of peripheral blood (PB) CD34+ cells. CD34
      enumeration is expensive, requires expertise and takes a minimum of 1-2 h to
      perform. The Sysmex XE2100 is an automated haematology analyser that can rapidly
      and inexpensively identify haematopoietic progenitor cell (HPC) populations in
      PB. The aim of this study was to examine if HPC can be used to optimize timing of
      PBSC harvest. MATERIALS AND METHODS: White blood cell (WBC), HPC and CD34 counts
      were determined in a total of 60 mobilized donors. Data were analysed to examine
      the utility of WBC and HPC counts in predicting preharvest CD34+ counts. RESULTS:
      In adults presenting for autologous collection, a PB HPC threshold of > 30/microl
      predicts a preharvest CD34+ count of > 20/microl with sensitivity of 86% and
      positive predictive value (PPV) of 100%. Among paediatric patients with a
      diagnosis of neuroblastoma, an HPC threshold of > 16/microl yielded sensitivity
      and PPV of 100%, while in children with other diagnoses, an HPC cut-off of >
      44/microl yielded sensitivity and PPV of 67% and 100%, respectively. Eighty per
      cent of adequately mobilized allogeneic donors were identified using an HPC
      threshold > 15/microl, with a PPV of 100%. PB WBC can also aid in predicting CD34
      counts in most patient groups, albeit with lower sensitivity than HPC.
      CONCLUSION: By virtue of being a sensitive and accurate predictor of preharvest
      CD34+ counts, our data support the use of the HPC parameter in optimizing the
      timing of PBSC harvest.

PMID- 19392782
TI  - Frequency, risk stratification and therapeutic management of acute post-traumatic
      coagulopathy.
AB  - BACKGROUND: Uncontrolled haemorrhage is still responsible for more than 50% of
      all trauma-related deaths within the first 48 h after hospital admission.
      Clinical observations together with recent research resulted in a new
      appreciation of the central role of coagulopathy in acute trauma care. A synopsis
      of different analyses based on datasets from severely multiple-injured patients
      derived from the TR-DGU database (Trauma Registry of the Deutsche Gesellschaft
      fur Unfallchirurgie (DGU)/German Society of Trauma Surgery) with respect to
      incidence, risk stratification and therapeutic management of acute post-traumatic
      coagulopathy is presented. METHODS: Retrospective analyses based on datasets from
      severely multiple-injured patients derived from the TR-DGU database and
      development/validation of a scoring system (TASH score = trauma-associated severe
      haemorrhage) that allows an early and reliable estimation for the probability of
      massive transfusion as a surrogate for life-threatening haemorrhage after severe
      multiple injuries. RESULTS/CONCLUSION: There is a high frequency of acute post
      traumatic coagulopathy already present upon ER admission which is associated with
      significant morbidity and mortality in multiple-injured patients. The TASH score
      is recognized as an easy-to-calculate and valid scoring system to predict the
      individual's probability for massive transfusion and thus ongoing life
      threatening haemorrhage at a very early stage after severe multiple injuries. An
      early aggressive management of acute post-traumatic coagulopathy including a more
      balanced administration of blood products to favour improved outcome is
      advocated.

PMID- 19392783
TI  - New developments in the antiviral treatment of hepatitis C.
AB  - Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and
      hepatocellular carcinoma. HCV is endemic in most parts of the world, with an
      estimated 170 million people infected worldwide and 3-4 million new cases each
      year. HCV-related end-stage liver disease is now the main indication for liver
      transplantation in the USA and Western Europe. Unfortunately, no vaccine or
      immunoglobulin is available to prevent HCV infection. Currently, HCV treatment
      consists of the combined administration of pegylated interferon and ribavirin for
      a period of 24-48 weeks, resulting in complete viral eradication in 40-80% of
      patients, depending on genotype, viral load and patient characteristics. This
      therapy is often accompanied with side-effects that affect compliance and reduce
      treatment outcomes. Recently, reliable in vitro culture systems have been
      developed which accelerated antiviral therapy research. Many new specifically
      targeted antiviral therapies for hepatitis C (STAT-C) and treatment strategies
      are evaluated in clinical trials. These new antiviral agents are expected to
      improve treatment significantly with potentially shorter treatment duration. The
      most promising antiviral agents will be reviewed.

PMID- 19392784
TI  - Biochemical quality of the pharmaceutically licensed plasma OctaplasLG after
      implementation of a novel prion protein (PrPSc) removal technology and reduction
      of the solvent/detergent (S/D) process time.
AB  - BACKGROUND AND OBJECTIVES: A new chromatographic step for the selective binding
      of pathological prion proteins (PrP(Sc)) to an affinity ligand, developed and
      optimized for PrP(Sc) capture and attached to synthetic resin particles (PRDT,
      USA; ProMetic BioSciences Ltd, Isle of Man, UK) was implemented into the
      manufacturing process of the solvent/detergent (S/D) treated biopharmaceutical
      quality plasma Octaplas. MATERIALS AND METHODS: Pilot batches of Octaplas with
      the implemented chromatographic step [labelled as OctaplasLG (ligand gel)] were
      manufactured by Octapharma PPGmbH, Vienna, Austria. The biochemical quality was
      compared directly after manufacturing as well as after 18 months storage. All
      samples were tested on global coagulation parameters, fibrinogen levels,
      activities of coagulation factors and protease inhibitors, ADAMTS13 levels, as
      well as markers of activated coagulation and fibrinolysis. In addition, von
      Willebrand factor multimeric analysis was performed. RESULTS: The incorporation
      of this novel chromatography into the large-scale routine manufacturing process
      was shown to be technically feasible and the performance of the column was
      assessed to be excellent. The biochemical studies showed that Octaplas and
      OctaplasLG produced without and with the new column, respectively, demonstrate an
      identical biochemical quality. OctaplasLG remained stable over a period of 18
      months stored frozen. A parallel reduction of the S/D virus inactivation step
      from 4-4.5 to 1-1.5 h led to significantly higher activities of plasmin
      inhibitor. CONCLUSION: The studies confirmed that the affinity ligand
      chromatography under the developed conditions can be introduced into the Octaplas
      manufacturing process, as a mean to reduce potentially present PrP(Sc), without
      hampering the proven quality of this product.

PMID- 19392785
TI  - Platelet concentrates produced from whole blood using the Atreus processing
      system.
AB  - BACKGROUND: The Atreus 2C+ system automates whole blood (WB) processing into a
      red cell concentrate, plasma and buffy coat (BC) suitable for platelet
      concentrate (PC) manufacture. This study compared the quality of PC made from BC
      using the Atreus, with those made by a manual method. STUDY DESIGN AND METHODS:
      WB was collected into Atreus disposables or standard bottom and top processing
      packs and held without active cooling for 26 h at 22 +/- 2 degrees C before
      processing, either with the Atreus, or using a centrifuge and press. BC were
      rested for 3 h and then 4 BC were pooled with one unit of plasma, mixed,
      centrifuged and pressed to make a pooled PC. The PC were analysed for quality
      markers to day 9 of storage. RESULTS: Platelet quality was good in both Atreus
      2C+ derived PC and control units throughout storage. Metabolic markers (pH, ATP
      and HSR) and activation markers (CD62P, sCD62P, annexin V binding,
      microparticles, GP IIb/IIIa) did not differ between the Atreus and control units.
      Atreus-derived PC had significantly lower platelet yields (302 +/- 59 x 10(9)
      platelets/unit; mean +/- standard deviation, n = 8) than control PC (411 +/- 76 x
      10(9) platelets/unit; P < 0.01), but met the UK guidelines for platelet yield.
      CONCLUSION: From these in vitro data, PC produced from buffy coats prepared using
      the Atreus appear suitable for clinical use, and WB may be held at ambient
      temperature overnight without the use of active cooling devices. Optimizing the
      secondary processing conditions to handle Atreus 2C+ derived BC may increase the
      platelet yield.

PMID- 19392786
TI  - DNA array analysis for red blood cell antigens facilitates the transfusion
      support with antigen-matched blood in patients with sickle cell disease.
AB  - BACKGROUND: Blood samples from patients with sickle cell disease (SCD) present to
      transfusion service with numerous antibodies, making the searching for compatible
      red blood cells (RBC) a challenge. To overcome this problem we developed an
      effective strategy to meet needs of supplying RBC-compatible units to SCD
      patients using DNA arrays. METHODS: We selected DNA samples from 144 SCD patients
      with multiple (receiving > 5 units) transfusions previously phenotyped for ABO,
      Rh(D, C, c, E, e), K1, Fy(a) and Jk(a). We also selected DNA samples from 948
      Brazilian blood donors whose ABO/RhD phenotype matched that of the patients. All
      samples were analysed by DNA array analysis (HEA Beadchip(TM), Bioarray
      Solutions) to determine polymorphisms associated with antigen expression for 11
      blood group systems (Rh, Kell, Kidd, Duffy, MNS, Dombrock, Lutheran, Landsteiner
      Wiener, Diego, Colton, Scianna); and one mutation associated with
      haemoglobinopathies. RESULTS: Based on genotype results we were able to predict
      phenotype-compatible donors needed in order to provide compatible units to this
      group of patients. Based on their ABO/Rh phenotype we were able to find in this
      pool of donors compatible units for 134 SCD patients. CONCLUSION: Blood group
      genotyping by DNA array contributes to the management of transfusions in SCD
      patients by facilitating the transfusion support with antigen-matched blood. It
      has the potential to improve the life of thousands of SCD-transfused patients by
      reducing mortality due to transfusion reactions and immunization.

PMID- 19392787
TI  - Distribution of KIR genes in the Iranian population.
AB  - Killer-cell immunoglobulin-like receptors (KIR) are a family of inhibitory and
      activating receptors that are expressed mainly by natural killer cells. The KIR
      gene family is highly polymorphic, and its genomic diversity is achieved through
      differences in gene content as well as allelic polymorphism. The number of KIR
      loci has been reported to be various among individuals and therefore resulting in
      different KIR haplotypes. This study represents the first report on the
      distribution of 17 presently defined KIR genes and pseudogenes in the Iranian
      population. In our study, 200 unrelated healthy individuals were KIR typed by a
      novel polymerase chain reaction-sequence-specific primers genotyping assay, and
      Iranian KIR genes distribution was compared with other ethnic groups. Over all,
      twenty-six different genotype profiles were found in our population and all KIR
      genes were observed. The most frequent non-framework KIR genes detected in our
      population were KIR2DL1 (96.5%), KIR3DL1 (91.5%), KIR2DS4 (91.5%) and the
      pseudogene KIR2DP1 (96.5%). The most commonly observed KIR genotype in Iranian
      population with a frequency of 27.5% consisted of KIR2DL1, KIR2DL3, KIR2DL4,
      KIR3DL1, KIR3DL2, KIR3DL3 and KIR2DS4 genes and the pseudogenes KIR2DP1 and
      KIR3DP1, which was compatible with a homozygote group-A haplotype. In addition,
      we found a new genotype (KIR2DL2, KIR2DL4, KIR2DL5, KIR3DL2, KIR3DL3, KIR2DS2,
      KIR2DS3, KIR2DS5, KIR3DS1 and KIR3DP1) in our samples. The results show that
      distribution of KIR genes in the Iranian population has common general features
      with the Caucasian populations studied before but still with unique, decreased or
      increased frequencies of several loci.

PMID- 19392788
TI  - HLA-DRB1 associations with disease susceptibility and clinical course in
      Australians with multiple sclerosis.
AB  - Human leucocyte antigen (HLA)-DRB1*1501 and other class II alleles influence
      susceptibility to multiple sclerosis (MS), but their contribution if any to the
      clinical course of MS remains uncertain. Here, we have investigated DRB1 alleles
      in a large sample of 1230 Australian MS cases, with some enrichment for subjects
      with primary progressive (PPMS) disease (n = 246) and 1210 healthy controls.
      Using logistic regression, we found that DRB1*1501 was strongly associated with
      risk (P = 7 x 10(-45)), as expected, and after adjusting for DRB1*1501, a
      predisposing effect was also observed for DRB1*03 (P = 5 x 10(-7)). Individuals
      homozygous for either DRB1*15 or DRB1*03 were considerably more at risk of MS
      than heterozygotes and non-carriers. Both the DRB1*04 and the DRB1*01/DRB1*15
      genotype combination, respectively, protected against PPMS in comparison to
      subjects with relapsing disease. Together, these data provide further evidence of
      heterogeneity at the DRB1 locus and confirm the importance of HLA variants in the
      phenotypic expression of MS.

PMID- 19392789
TI  - TNF block haplotypes associated with conserved MHC haplotypes in European, Asian
      and Australian Aboriginal donors.
AB  - Associations between major histocompatibility complex (MHC) ancestral haplotypes
      (AHs) and immunopathological diseases are traditionally ascribed to human
      leukocyte antigen (HLA) class I or class II alleles. However, polymorphisms in
      TNF and nearby genes in the central MHC can influence risk. We have defined TNF
      block haplotypes in Asian, European and Australian Aboriginal donors and shown
      conservation of TNF block haplotypes in geographically distinct populations,
      consistent with a common evolutionary origin. Here we show that most TNF block
      haplotypes do not align with a single MHC AH and associations often vary with
      ethnicity. This suggests more recent recombination events between the TNF block
      and the HLA alleles.

PMID- 19392790
TI  - Association of TIM4 promoter polymorphism -1419G>A with childhood asthma in a
      Chinese Han population.
AB  - TIM4, which is expressed on dendritic cells and macrophages, plays an important
      role in the proliferation of T helper type 2 (Th2) cells. Asthma, as a complex
      genetic disease, is thought to arise from the development of a Th2-lymphocyte
      predominant immune response. To evaluate the effects of the promoter
      polymorphisms (-1419G>A and -1609G>A) in TIM4 on asthma susceptibility, case
      control and family-based association studies were conducted by polymerase chain
      reaction and restriction fragment length polymorphism. Our results showed that
      TIM4 -1419G>A polymorphism was associated with asthma susceptibility in our study
      population (chi(2)= 9.88, P < 0.001, OR = 1.91, 95% CI 1.37-2.64). The -1419A/A
      and -1419A/G genotypes were observed more common in asthmatic group (6.3%, 41.8%)
      than in control group (1.7%, 29.3%). No significant difference was found in
      genotype and allele frequencies of TIM4 -1619G>A polymorphism between asthmatic
      and control groups. No association between the two SNPs and total serum IgE
      levels, lung function was observed. In conclusion, the present findings suggest
      that TIM4 -1419G>A polymorphism might be the genetic factor for the risk of
      childhood asthma in Chinese Han population.

PMID- 19392791
TI  - A novel HLA-Cw*07 variant, HLA-Cw*0760, identified by sequence-based typing in a
      bone marrow donor.
AB  - We report the identification of the novel allele HLA-Cw*0760 that was found
      during confirmatory high-resolution sequence-based typing of a bone marrow donor.
      The Cw*0760 allele has two nucleotide changes from Cw*070101 at positions 341 and
      343 in exon 2, resulting in two amino acid changes from Asp to Ala (codon 90: GAC
      ->GCC) and Gly to Arg (codon 91: GGG-->AGG).

PMID- 19392792
TI  - Identification of B*9550, a novel B*15 allele, in a Mexican bone marrow donor
      from Veracruz State.
AB  - Human leukocyte antigen-B*9550 is a novel allele identified in a Mexican Mestizo
      bone marrow donor from Veracruz.

PMID- 19392793
TI  - A novel duplex SSP-PCR typing method for KIR gene profiling.
AB  - Killer-cell immunoglobulin-like receptors (KIR) control the function of natural
      killer cells. The number and type of KIR genes are substantially variable among
      individuals. Sequence-specific primer-directed polymerase chain reaction (SSP
      PCR) based genotyping is the most commonly used method to assess the KIR gene
      content. However, it requires a minimum of 16 gene-specific amplifications and
      often yields false-negative results. Herein, we describe the development of a
      simple and efficient duplex SSP-PCR assay to identify the presence and absence of
      16 KIR genes. This system further distinguishes subsets of KIR2DS4 and KIR3DP1
      alleles. The assay was subjected to a blind validation using a panel of 78
      reference DNA standards from the UCLA KIR Exchange Program, which showed 100%
      specificity and accuracy. Compared with the conventional SSP typing methods, the
      present method is an accurate, simple, cost-effective and labor-saving KIR
      genotyping method for high volume testing.

PMID- 19392794
TI  - Two new HLA-DQB alleles routinely identified by sequence-based typing:
      DQB1*030103 and DQB1*0505.
AB  - Here, we report the identification of two novel human leukocyte antigen-DQB1
      alleles, DQB1*030103 and DQB1*0505, found by routine typing using commercial
      kits.

PMID- 19392795
TI  - Identification of HLA-B*5410 in Taiwan.
AB  - A new human leukocyte antigen-B allele, B*5410, has been detected in Taiwan. It
      has one nucleotide change from B*5401 at codon 156 (CTG-->CGG), resulting in one
      amino acid change (L-->R).

PMID- 19392796
TI  - Discovery of a novel HLA-Cw*08 allele, Cw*0817.
AB  - This report describes the discovery and characterization of the HLA-Cw*0817
      allele.

PMID- 19392797
TI  - TNF, LTA and TGFB1 genotype distributions among acute graft-vs-host disease
      subsets after HLA-matched unrelated hematopoietic stem cell transplantation: a
      pilot study.
AB  - Cytokine single nucleotide polymorphisms and consequent production levels have
      been associated with acute graft-vs-host disease (aGVHD) development. The aim of
      this pilot study was to determine whether polymorphisms in tumor necrosis factor
      (TNF), lymphotoxin alpha (LTA) and transforming growth factor beta 1 (TGFB1)
      showed any association with aGVHD severity. Novel alleles and polymorphisms were
      identified for each cytokine locus. Genotype distributions were examined in 38
      recipient-donor pairs (all chronic myelogenous leukemia in the first chronic
      phase) with either low-grade (grades 0-I) or high-grade (grades III-IV) aGVHD.
      Although no significant differences were found, some trends were noted in
      genotype distributions among aGVHD-grade groups. Power calculations determined
      that substantially more pairs would be required to show significant associations
      in distributions among aGVHD-grade groups.

PMID- 19392798
TI  - Invariant natural killer T cells: innate-like T cells with potent
      immunomodulatory activities.
AB  - Invariant natural killer T (iNKT) cells are a subset of T lymphocytes that react
      with glycolipid antigens presented by the major histocompatibility complex class
      I-related glycoprotein CD1d. Although iNKT cells express an antigen-specific
      receptor of the adaptive immune system, they behave more like cells of the innate
      immune system. A hallmark of iNKT cells is their capacity to produce copious
      amounts of immunoregulatory cytokines quickly after activation. The cytokines
      produced by iNKT cells can influence the level of activation of many cell types
      of the innate and adaptive immune systems as well as the quality of an adaptive
      immune response. As such, iNKT cells have emerged as important regulators of
      immune responses, playing a role in microbial immunity, autoimmunity, tumor
      immunity, and a variety of inflammatory conditions. Although several endogenous
      and exogenous glycolipid antigens of iNKT cells have been identified, how these
      glycolipids orchestrate iNKT-cell functions remains poorly understood.
      Nevertheless, iNKT cells hold substantial promise as targets for development of
      vaccine adjuvants and immunotherapies. These properties of iNKT cells have been
      investigated most extensively in mouse models of human disease using the marine
      sponge-derived agent alpha-galactosylceramide (alpha-GalCer) and related iNKT
      cell antigens. While these preclinical studies have raised enthusiasm for
      developing iNKT-cell-based immunotherapies, they also showed potential health
      risks associated with iNKT cell activation. Although alpha-GalCer treatment in
      humans was shown to be safe in the short term, further studies are needed to
      develop safe and effective iNKT-cell-based therapies.

PMID- 19392799
TI  - MHC class I chain-related gene A transmembrane polymorphism in Spanish women with
      breast cancer.
AB  - The NKG2D-major histocompatibility complex class I-related chain A (MICA) system
      plays a key role in the antitumoral immune response. We studied five alleles of a
      microsatellite in the MICA transmembrane region; one of which (MICA-A5.1) gives
      rise to a truncated protein. The MICA-A5 allele was reduced in breast cancer
      patients compared with healthy controls (P = 0.04). Given the association between
      the HLA-B7 allele and the susceptibility to breast cancer in our area, we also
      analyzed the distribution of the frequency of the MICA alleles in human leukocyte
      antigen (HLA)-B7 patients compared with patients with the other alleles. The MICA
      A5.1 allele was increased in HLA-B7 patients (P = 0.0003). These results suggest
      that the MICA-A5 allele appears to confer protection against human breast cancer
      and that the MICA-A5.1 appears to increase the susceptibility to breast cancer in
      HLA-B7 patients in our area.

PMID- 19392800
TI  - Association of KIR2DL2 polymorphism rs2756923 with type 1 diabetes and
      preliminary evidence for lack of inhibition through HLA-C1 ligand binding.
AB  - Killer cell immunoglobulin-like receptors (KIRs) on chromosome 19q13.4 regulate
      the function of not only human natural killer (NK) cells but also T cells. An
      increase in activating KIR- human leucocyte antigen ligand pairs has been
      associated with an additional risk to develop type 1 diabetes (T1D). T1D families
      [n = 184 (552 individuals); n = 176 (528 subjects)], unrelated T1D patients (n =
      380; n = 394) and healthy controls (n = 315; n = 401) from Germany and Belgium,
      respectively, were genotyped for the rs2756923 polymorphism within the KIR gene
      cluster haplotype B in exon 8 of the KIR2DL2 gene. We observed in both Germans
      and Belgians an overtransmission of the allele 'G' of the KIR2DL2-rs2756923
      polymorphism (64.2% vs 35.8%, P = 3 x 10(-4) and 60.0% vs 40.0%, P = 0.02,
      respectively). In addition, this allele was more frequent in German patients than
      in healthy controls (78.4% vs 21.6%, P = 1 x 10(-3)). Preliminary results from a
      cytotoxicity assay suggest that inhibition of NK-cell cytotoxicity may be
      impaired in individuals carrying the rs2756923 G allele. These data suggest a
      potential role of the KIR2DL2-rs2756923 polymorphism in T1D in Germans and
      Belgians.

PMID- 19392801
TI  - Role of polymorphisms in the TNFRSF13B (TACI) gene in Spanish patients with
      immunoglobulin A deficiency.
AB  - Mutations in the TNFRSF13B (TACI) gene have been associated with common variable
      immunodeficiency, and a role in immunoglobulin A deficiency (IgAD) has also been
      suggested. We aimed at studying the role of several polymorphisms along this gene
      in IgAD susceptibility. Three TNFRSF13B mutations (C104R, A181E and R202H) and
      eight additional single nucleotide polymorphisms in the gene were genotyped in
      338 Spanish IgAD patients and 553 ethnically matched healthy controls and tested
      for association. Data from parents of 114 IgAD patients were also collected and
      used for additional analysis. No statistically significant differences were
      observed after comparing patients and controls for any single nucleotide
      polymorphism analysed. Therefore, our work seems to discard a role of TNFRSF13B
      mutations in IgAD, concordantly with the most recent published studies.

PMID- 19392802
TI  - The association between HLA-A, -B alleles and major histocompatibility complex
      class I polymorphic Alu insertions in four populations in China.
AB  - The study of the association between polymorphic Alu insertions [human leukocyte
      antigen (HLA)-Alu] at five loci and HLA class I alleles at two loci allows for
      better identification of the origins and evolution of HLA class I region
      haplotypes in different populations. In the present study, we determined the
      frequencies of five HLA-Alus and their associations with HLA-A and -B alleles in
      Han, Wa, Maonan, and Jinuo populations. Our results showed a strong association
      between AluHG insertion and HLA-A*02 in all populations studied; however, the
      associations between AluHJ insertion and HLA-A*1101 and HLA-A*2402 and AluHF
      insertion and HLA-A*2601 were only observed in Han. The AluMICB insertion showed
      a strong association with HLA-B*5502 in Han, Maonan, and Jinuo. HLA-A*0101, HLA
      A*0201, HLA-A*0203, HLA-A*1101, HLA-A*2402, HLA-A*2601, and HLA-A*3101 alleles
      were associated with one or more of the three different Alu elements within the
      alpha block as independent haplotypes, and HLA-A*0101, HLA-A*0201, HLA-A*0203,
      HLA-A*1101, and HLA-A*2402 alleles were associated with at least two different
      Alu insertions as a haplotype within the alpha block. We conclude that the HLA
      class I region haplotypes of the four populations were derived from different
      progenitor haplotypes, and relatively high rates of recombination between
      individuals with HLA-A alleles and different HLA-Alus occurred in this region.

PMID- 19392803
TI  - Characterization of a new HLA-C allele in a Chinese family by sequence-based
      typing: HLA-Cw*0348.
AB  - The novel human leukocyte antigen (HLA)-Cw*0348 allele was identified by sequence
      based typing in a Chinese family. This allele shows that the sequences of exons 1
      3 of HLA-Cw*0348 are identical to those of HLA-Cw*030401 except for a nucleotide
      substitution that changes CCG to CTG at codon 57, resulting in an amino acid
      change from Pro to Leu in the protein, and this is a unique nucleotide change
      among the HLA-C alleles, suggesting a point mutation mechanism. The extended
      haplotype carrying the new allele was deduced from the family group typing and
      defined as A*110101, B*1301, Cw*0348, DRB1*0405, and DQB1*0402.

PMID- 19392804
TI  - HLA-A*1136 and HLA-A*1138 were identified by polymerase chain reaction sequence
      based typing in Chinese individuals.
AB  - Two human leukocyte antigen (HLA)-A*11 variant alleles were identified in Chinese
      individuals. HLA-A*1136 shows only one nucleotide difference from A*110101 in
      exon 3 at position 368, resulting in an amino acid change from His to Cys at
      codon 99. HLA-A*1138 has two nucleotides change at positions 570 and 571 compared
      with A*110201, resulting in amino acids change from Glu to Asp at codon 166 and
      Trp to Gly at codon 167.

PMID- 19392805
TI  - Characterization of three novel HLA alleles, HLA-B*4613, HLA-B*4614 and HLA
      B*4618, in Chinese individuals.
AB  - Three novel alleles, human leukocyte antigen (HLA)-B*4613, HLA-B*4614 and HLA
      B*4618, were identified in Chinese individuals. HLA-B*4613 shows four nucleotides
      difference from B*460101, resulting in two amino acids change from Glu to Val at
      codon 152 and Trp to Leu at codon 156. HLA-B*4614 has a single nucleotide
      difference at position 97 T-->C compared with HLA-B*460101, with an amino acid
      change from Tyr to His at codon 9. HLA-B*4618 shares the sequence of exon 2 with
      B*4601 and sequences of exons 3 and 4 with B*55, B*54 or B*59, together resulting
      in eight amino acids change compared with HLA-B*460101.

PMID- 19392806
TI  - Identification of a novel allele HLA-DRB1*0478 by sequence-based typing in a
      Chinese individual.
AB  - A novel allele HLA-DRB1*0478 is described. This variant has one nucleotide
      substitution in exon 2. This mutations result in an amino acid substitution at
      condon 70 (CAG --> CGG) from Gln to Arg.

PMID- 19392808
TI  - Outcomes for 236 patients from a 2-year early intervention in psychosis service.
AB  - OBJECTIVE: To examine: i) changes in key outcome measures over time in treatment
      in a representative first-episode psychosis treatment cohort and ii) baseline
      predictors of service disengagement. METHOD: Baseline characteristics of 236
      patients were examined for associations with outcomes over time using generalized
      estimating equation models. The data on disengagement were analysed using
      logistic regression. RESULTS: After controlling for admission scores, patients
      showed consistently improved outcomes while in treatment on functional recovery
      (unemployment, P < 0.01; HoNOS, P < 0.001; the Quality of Life Scale, P < 0.001;
      GAF, P < 0.05) but not symptomatology (as assessed by the PANSS and substance
      abuse). The 64 (33%) who disengaged were more likely to be unemployed (P < 0.01)
      and have higher HoNOS (P < 0.01) and GAF (P < 0.05) scores at baseline.
      CONCLUSION: This evaluation has shown significant improvements in psychosocial
      functioning but not psychopathology during treatment at an Early Intervention for
      Psychosis Service. Despite attempts to retain patients, there is a high rate of
      treatment discontinuation.

PMID- 19392807
TI  - Evaluating the potential impact of mismatches outside the antigen recognition
      site in unrelated hematopoietic stem cell transplantation: HLA-DRB1*1454 and
      DRB1*140101.
AB  - DNA sequencing of 268 individuals drawn from four US populations carrying two
      unresolved DRB1*14 alleles differing only outside the antigen recognition site
      identified DRB1*1454 in the majority. A database of 4222 human leukocyte antigen
      (HLA)-matched hematopoietic stem cell transplantation donor-recipient pairs was
      queried to determine the number likely mismatched for DRB1*140101/DRB1*1454 but
      matched for class I loci. A power calculation suggests that more than 88,000
      transplants among European Americans will be needed to identify sufficient 7/8
      allele-matched pairs to evaluate the impact of the DRB1*140101/DRB1*1454 mismatch
      on transplant outcome. Molecular modeling of the HLA-DR interaction with the T
      cell receptor and with CD4 suggests that the amino acid substitution
      distinguishing the two alleles will have minimal impact on allorecognition.

PMID- 19392809
TI  - Is bipolar II depression phenotypically distinctive?
AB  - OBJECTIVE: We examine the depressive symptom profile of bipolar II disorder
      patients compared with a comparator (composite) group of those with unipolar
      depression, with stratification by melancholic and non-melancholic subtypes.
      METHOD: Out-patients (n = 394) attending a specialist depression clinic comprised
      the sample. Data on severity and prototypic status of depressive symptoms were
      analysed. RESULTS: Age-matched analyses revealed minimal differentiation between
      bipolar II and composite unipolar groups. Stratified analyses suggested that
      'bipolar II depression' more closely approximated melancholic depression in terms
      of psychomotor and cognitive slowing. Severity-based analyses and prototypic
      symptom patterns yielded differing results, suggesting that definition of bipolar
      II depression is influenced by rating strategies, and age. CONCLUSION: We found
      limited differentiation of bipolar II depression from unipolar, melancholic and
      non-melancholic depression. Differences suggested previously may reflect age,
      gender and severity differences, highlighting the need for appropriately matched
      groups in defining bipolar II depression.

PMID- 19392810
TI  - Rhabdomyolysis and brain ischemic stroke in a heroin-dependent male under
      methadone maintenance therapy.
AB  - OBJECTIVE: There are several complications associated with heroin abuse, some of
      which are life-threatening. Methadone may aggravate this problem. METHOD: A
      clinical case description. RESULTS: A 33-year-old man presented with
      rhabdomyolysis and cerebral ischemic stroke after intravenous heroin. He had used
      heroin since age 20, and had used 150 mg methadone daily for 6 months. He was
      found unconsciousness at home and was sent to our hospital. In the ER, his opiate
      level was 4497 ng/ml. In the ICU, we found rhabdomyolysis, acute renal failure
      and acute respiratory failure. After transfer to an internal ward, we noted
      aphasia and weakness of his left limbs. After MRI, we found cerebral ischemic
      infarction. CONCLUSION: Those using methadone and heroin simultaneously may
      increase risk of rhabdomyolysis and ischemic stroke. Patients under methadone
      maintenance therapy should be warned regarding these serious adverse events.
      Hypotheses of heroin-related rhabdomyolysis and stroke in heroin abusers are
      discussed.

PMID- 19392811
TI  - A randomized study of massed three-week cognitive behavioural therapy schedule
      for panic disorder.
AB  - OBJECTIVE: To compare the efficacy of massed vs. spaced group cognitive
      behavioural therapy (CBT) for patients with panic disorder with or without
      agoraphobia (PD). METHOD: Thirty-nine PD patients were randomly assigned to
      massed group CBT (daily 4-h sessions in week 1, two 2-h sessions in week 2 and
      one 2-h session in week 3) or traditional spaced weekly group CBT (13
      consecutive, weekly 2-h sessions). The content and number of hours in the two
      treatment schedules were identical. Outcome was assessed after treatment, and at
      3, 6 and 18 months of follow-up. RESULTS: Both treatment groups achieved
      significant improvement on all measures with large pre- to post-treatment and pre
      treatment to follow-up effect sizes. No between-group differences were
      registered. Adherence and patient satisfaction did not differ between groups.
      CONCLUSION: The massed, 3-week group CBT schedule proved to be effective and
      feasible for PD patients with outcomes comparable with that of standard, spaced
      group CBT.

PMID- 19392812
TI  - Achieving symptomatic remission in out-patients with schizophrenia--a
      naturalistic study with quetiapine.
AB  - OBJECTIVE: Symptomatic remission was defined as a score of mild or less on each
      of eight key schizophrenia symptoms on the Positive and Negative Syndrome Scale
      (PANSS-8). To evaluate the symptomatic remission criterion in clinical practice
      and to determine predictors for achieving symptomatic remission, a 12-week non
      interventional study (NIS) with quetiapine was conducted in Germany. METHOD: For
      the comparison of patients with and without symptomatic remission,
      sociodemographic and clinical variables of 693 patients were analyzed by logistic
      regression for their predictive value to achieve remission. RESULTS: Four hundred
      and four patients (58.3%) achieved symptomatic remission after 12 weeks'
      treatment with quetiapine. Remission was significantly predicted by a low degree
      of PANSS-8 total score, PANSS single items blunted affect (N1), social withdrawal
      (N4), lack of spontaneity (N6), mannerism and posturing (G5), and low disease
      severity (CGI-S) at baseline. Predictors of non-remission were older age,
      diagnosis of schizophrenic residuum, multiple previous episodes, longer duration
      of current episode, presence of concomitant diseases, and alcohol abuse.
      CONCLUSION: This study demonstrated that the majority of schizophrenia out
      patients achieved symptomatic remission after 12 weeks treatment and confirms the
      importance of managing negative symptoms in order to achieve disease remission.

PMID- 19392814
TI  - Folic acid efficacy as an alternative drug added to sodium valproate in the
      treatment of acute phase of mania in bipolar disorder: a double-blind randomized
      controlled trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of adding folic
      acid to sodium valproate in the acute phase of mania. METHOD: Following a double
      blind randomized controlled trial, 88 clinically manic patients with diagnosis of
      type I bipolar disorder (BID) were divided randomly into two groups (case and
      control). The case group was treated with folic acid and sodium valproate and the
      control group with sodium valproate and placebo. The severity of mania was
      assessed using the Young Mania Rating Scale (YMRS) at the beginning and end of
      the first, second and third weeks of the study. RESULTS: The case group's mean
      manic YMRS measurements (SD) before the initiation of therapy and in the first,
      second and third weeks of treatment were 34.0 +/- 7.7, 26.7 +/- 2.1, 18.1 +/- 2.1
      and 7.1 +/- 0.9 respectively. The control group's measurements were 34.7 +/- 3.8,
      27.3 +/- 2.3, 20.7 +/- 2.5 and 10.1 +/- 1.1. There was a statistically
      significant difference in YMRS scaling results between the case and control
      groups after 3 weeks of treatment (7.1 +/- 0.9 vs. 10.1 +/- 1.1, P = 0.005).
      CONCLUSION: Based on our findings, folic acid seems to be an effective adjuvant
      to sodium valproate in the treatment of the acute phase of mania in patients with
      bipolar disorder.

PMID- 19392813
TI  - Early intervention in patients at ultra high risk of psychosis: benefits and
      risks.
AB  - OBJECTIVE: Prediction of transition to psychosis in the prodromal phase of
      schizophrenia has raised interest in intervention prior to the onset of frank
      psychosis. The aim of this review was to examine whether interventions in the
      prodromal phase have a favourable benefit/risk ratio. METHOD: A literature search
      in PubMed, EMBASE and PsycINFO was performed. RESULTS: Three randomized clinical
      trials with antipsychotic medication and/or cognitive behavioural therapy as
      clinical intervention suggested a positive effect at the end of treatment, but no
      significant differences were found at the end of follow-up periods from 1 to 4
      years. Naturalistic studies present a hypothesis about a possible preventive
      effect of antidepressive medication. The results of eight other studies are more
      difficult to interpret. Side-effects of antipsychotic medication and non
      adherence with medication are essential problems. CONCLUSION: At the present
      time, the data concerning the benefits and risks do not justify prodromal
      intervention as standard clinical practice.

PMID- 19392816
TI  - Identification of SNPs in porcine genes expressed during porcine respiratory and
      reproductive syndrome virus infection.

PMID- 19392815
TI  - Refined localization of the Escherichia coli F4ab/F4ac receptor locus on pig
      chromosome 13.
AB  - Diarrhoea in newborn and weaned pigs caused by enterotoxigenic Escherichia coli
      (ETEC) expressing F4 fimbriae leads to considerable losses in pig production. In
      this study, we refined the mapping of the receptor locus for ETEC F4ab/F4ac
      adhesion (F4bcR) by joint analysis of Nordic and Swiss data. A total of 236 pigs
      from a Nordic experimental herd, 331 pigs from a Swiss experimental herd and 143
      pigs from the Swiss performing station were used for linkage analysis. Genotyping
      data of six known microsatellite markers, two newly developed markers (MUC4gt and
      HSA125gt) and an intronic SNP in MUC4 (MUC4-8227) were used to create the linkage
      map. The region for F4bcR was refined to the interval SW207-S0075 on pig
      chromosome 13. The most probable position of F4bcR was in the SW207-MUC4 region.
      The order of six markers was supported by physical mapping on the BAC fingerprint
      contig from the Wellcome Trust Sanger Institute. Thus, the region for F4bcR could
      be reduced from 26 to 14 Mb.

PMID- 19392817
TI  - A population study of a mutation allele associated with cone-rod dystrophy in the
      standard wire-haired dachshund.
AB  - Cone-rod dystrophy in the standard wire-haired dachshund (SWHD) is inherited as a
      simple autosomal recessive trait and the recently discovered mutation is
      widespread within the SWHD population in Norway and other Scandinavian countries.
      The gene frequency was estimated to be 4.8%. On the basis of the assumption that
      the size of the ancestral haplotype around a mutation is inversely correlated
      with the number of generations since the mutation arose, we have found that the
      mutation is of a relatively recent origin. The conserved haplotype was found to
      be 8 Mb in size and therefore we estimate that the mutation arose roughly eight
      generations (approximately 37 years) ago. This indicates that the mutation arose
      after breed separation.

PMID- 19392818
TI  - DOGSET: pre-designed primer sets for fine-scale mapping and DNA sequence
      interrogation in the dog.
AB  - DOGSET is an online resource that provides access to primer sequences that have
      been computationally mined from the reference genome using heuristic algorithms.
      The electronic repository includes PCR primers corresponding to 32,135 markers
      for genetic mapping and 334,657 sequence-tagged gene elements for targeted re
      sequencing and mutation discovery. A customized report that tailors primer design
      to wet bench protocols can be exported for a region of interest by specifying
      genome coordinates in a graphical user interface.

PMID- 19392819
TI  - The G allele at the c.-312A>G SNP in the EDG1 gene associated with high marbling
      in Japanese Black cattle is at a low frequency in breeds not selected for
      marbling.

PMID- 19392820
TI  - Female segregation patterns of the putative Y-chromosome-specific microsatellite
      markers INRA124 and INRA126 do not support their use for cattle population
      studies.
AB  - Here we tested the segregation and paternal compatibility of markers INRA124 and
      INRA126 on female DNA in 10 different cattle families, in order to clarify the
      usefulness of these microsatellites for the study of male-mediated population
      processes in cattle. Their performance was compared with that of four
      microsatellites located in the PAR-BTAY (UMN0108, UMN0803, UMN0929 and UMN0905)
      and another one male-specific microsatellite (INRA189). INRA124 and INRA126
      amplified the same sized fragment in both sexes. Same size alleles were sequenced
      and the high homology found allowed us to rule out non-specific female
      amplification. INRA124 showed full parental compatibility, whilst the locus
      INRA126 showed 55% parental incompatibility. Based on these observations, it is
      recommended that markers INRA124 and INRA126 should not be used in studies to
      characterize male-mediated genetic events in cattle.

PMID- 19392821
TI  - Refinement of a quantitative trait locus on equine chromosome 5 responsible for
      fetlock osteochondrosis in Hanoverian warmblood horses.
AB  - In this report, we provide 29 new informative microsatellites distributed over a
      region of 21 Mb on horse chromosome (ECA) 5 and refine a quantitative trait locus
      (QTL) for fetlock osteochondrosis dissecans (OCD) to a genome-wide significant
      interval between 78.03 and 90.23 Mb on ECA5. Genotyping was performed in 211
      Hanoverian warmblood horses from 14 paternal half-sib groups. Within this OCD
      QTL, collagen type XXIV alpha 1 was identified as a potential functional
      candidate gene for equine osteochondrosis. This report is a further step towards
      unravelling the genes that cause equine osteochondrosis.

PMID- 19392822
TI  - Characterization and genetic analysis of bovine alpha S1-casein I variant.
AB  - The aim of this study was to identify the molecular genetic origin underlying the
      I variant of alpha(s1)-casein and to develop a DNA-based test for this
      polymorphism as a tool for genetic analyses independent of milk sample testing.
      All coding exons and flanking regions of the alpha(s1)-casein gene were sequenced
      in DNA samples from cattle of known alpha(s1)-casein genotypes (BI, CI, II, CC),
      determined by isoelectric focusing of milk samples. A nucleotide substitution
      (A>T) in exon 11 (g.19836A>T) leads to the exchange of Glu with Asp at amino acid
      position 84 of the mature protein (p.Glu84Asp) and perfectly co-segregated with
      the presence of the alpha(s1)-casein I variant in the milk of the analysed
      animals. Genotyping of a total of 680 DNA samples from 31 Bos taurus and Bos
      indicus cattle breeds and from Bos grunniens, Bison bison and Bison bonasus by
      restriction fragment length polymorphism analysis revealed the occurrence of Asp
      at position 84 at low frequencies in Bos taurus and Bos indicus breeds and
      established its origin from the alpha(s1)-casein C variant (p.Glu192Gly). Ten
      different intragenic haplotypes in the gene region from intron 8 to intron 12
      were observed by sequencing, of which two occurred in Bison bison and one in
      Bison bonasus only. Using available casein gene complex information, an
      association of Asp at position 84 to beta-casein A(2) and kappa-casein B was
      shown in the Bos indicus breed Banyo Gudali. Taken together, we can postulate
      that the alpha(s1)-casein variant I is caused by a non-synonymous nucleotide
      substitution in exon 11 of the gene and that it originated within Bos indicus and
      spread to Bos taurus subsequently.

PMID- 19392823
TI  - Molecular characterization of swine leucocyte antigen class I genes in outbred
      pig populations.
AB  - The highly polymorphic swine leucocyte antigen (SLA) genes are one of the most
      important determinants in swine immune responses to infectious diseases,
      vaccines, and in transplantation success. Study of SLA influence requires
      accurate and effective typing methods. We developed a simple and rapid method to
      type alleles at the three classical SLA class I loci (SLA-1, SLA-3 and SLA-2)
      using the PCR-sequence-specific primer (PCR-SSP) strategy. This typing system
      relies on 47 discriminatory PCR primer pairs designed to amplify the SLA class I
      alleles by groups that have similar sequence motifs. We applied this low
      resolution group-specific typing method to characterize the SLA class I alleles
      present in three outbred pig populations (n = 202). Alleles from 24 class I
      allele groups corresponding to 56 class I genotypes were detected. We also
      identified 23 low-resolution SLA class I haplotypes in these pigs and found
      haplotypes Lr-1.0 (SLA-1*01XX-SLA-3*01XX-SLA-2*01XX) and Lr-4.0 (SLA-1*04XX-SLA
      3*04XX-SLA-2*04XX) in all three pig populations with a high prevalence. Over 80%
      of the pigs examined (n = 162) were found to bear at least one of these
      haplotypes, resulting in a combined haplotype frequency of nearly 50%. This PCR
      SSP-based typing system demonstrates a reliable and unambiguous detection of SLA
      class I alleles, and can be used to effectively investigate the SLA diversity in
      outbred pig populations. It will help to identify the role of SLA antigens in
      disease-resistant pigs and may facilitate the development of effective vaccines.

PMID- 19392824
TI  - A frameshift mutation in the coding region of the myostatin gene (MSTN) affects
      carcass conformation and fatness in Norwegian White Sheep (Ovis aries).
AB  - Mutations in the coding region of the myostatin gene (MSTN) are known to cause an
      increased muscle mass (IMM) phenotype in several mammals, including mice, dogs,
      cattle and humans. In sheep, a mutation in the 3'-UTR region introducing a
      microRNA target site has been reported to cause an IMM-like phenotype because of
      downregulation of translation. Here we report a novel single base deletion in the
      coding region of the myostatin gene causing an IMM phenotype in Norwegian White
      Sheep, characterized by a high carcass conformation class and low fat class
      (EUROP classification system). The deletion disrupts the reading frame from amino
      acid (aa) position 320, ending in a premature stop codon in aa position 359. In
      our material, these MSTN mutations segregated in a pattern showing that they
      reside in two different haplotypes. The phenotypic effect of the single base
      deletion is more profound than that of the 3'-UTR mutation.

PMID- 19392825
TI  - Development of 40 microsatellite markers in spotted halibut (Verasper variegatus)
      and the cross-species amplification in barfin flounder (Verasper moseri ).

PMID- 19392826
TI  - A genome scan for quantitative trait loci affecting three ear traits in a White
      Duroc x Chinese Erhualian resource population.
AB  - Chinese Erhualian pigs have larger and floppier ears compared with White Duroc
      pigs (small, half- or fully-pricked ears). To identify quantitative trait loci
      (QTL) for ear weight and area as well as erectness, a genome-wide scan with 194
      microsatellites was performed in a White Duroc x Chinese Erhualian resource
      population (>1000 F(2) animals). Twenty-three genome-wide significant QTL and 12
      suggestive QTL were identified. All QTL for ear erectness and size detected in
      two previous studies, bar two on SSC6 and 9, were confirmed here. The 1% genome
      wide significant QTL at 70 cM on SSC5 and at 58 cM on SSC7 have profound and
      pleiotropic effects on the three ear traits, with Erhualian alleles increasing
      weight and area but decreasing erectness. Notably, the 95% confidence interval of
      the QTL for weight and area on SSC7 spanned only 3 cM. New QTL reaching 1% genome
      wide significance were found on SSC8 (at 37 cM) for all three ear traits, on SSC4
      and 16 for weight and area, and on SSCX for area. Unexpectedly, Erhualian alleles
      at these loci were associated with lighter and smaller or erect ear. Some new
      suggestive QTL were also found on other chromosome regions. Almost all the QTL
      for weight and area had essentially additive effects, while the QTL for erectness
      on SSC2, 5 and 7 showed not only additive effects but also partial dominance
      effects of Erhualian alleles. The two most significant QTL on SSC7 and SSC5 could
      be promising targets for fine mapping and identification of the causative
      mutations.

PMID- 19392827
TI  - A functional genomics approach to evaluate candidate genes located in a QTL
      interval for milk production traits on BTA6.
AB  - The potential genetic and economic advantage of marker-assisted selection for
      enhanced production in dairy cattle has provided an impetus to conduct numerous
      genome scans in order to identify associations between DNA markers and future
      productive potential. One area of focus has been a quantitative trait locus on
      bovine chromosome 6 (BTA6) found to be associated with milk yield, milk protein
      and fat percentage, which has been subsequently fine-mapped to six positional
      candidate genes. Subsequent investigations have yet to resolve which of the
      potential positional candidate genes is responsible for the observed associations
      with productive performance. In this study, we analysed candidate gene expression
      and the effects of gene knockdown on expression of beta- and kappa-casein mRNA in
      a small interfering RNA transfected bovine in vitro mammosphere model. From our
      expression studies in vivo, we observed that four of the six candidates (ABCG2,
      SPP1, PKD2 and LAP3) exhibited differential expression in bovine mammary tissue
      over the lactation cycle, but in vitro functional studies indicate that
      inhibition of only one gene, SPP1, had a significant impact on milk protein gene
      expression. These data suggest that the gene product of SPP1 (also known as
      osteopontin) has a significant role in the modulation of milk protein gene
      expression. While these findings do not exclude other positional candidates from
      influencing lactation, they support the hypothesis that the gene product of SPP1
      is a significant lactational regulatory molecule.

PMID- 19392828
TI  - Effect of single nucleotide polymorphisms of CAPN1 and CAST genes on meat traits
      in Nellore beef cattle (Bos indicus) and in their crosses with Bos taurus.
AB  - The objectives of this work were to study the segregation of single nucleotide
      polymorphisms of the calpain 1, large subunit (CAPN1) and calpastatin (CAST)
      genes in Nellore (Bos indicus) and Nellore xBos taurus beef cattle, as well as to
      evaluate their effects on meat traits. For this, 300 animals, including 114
      Nellore, 67 Angus x Nellore, 44 Rubia Gallega x Nellore, 41 Canchim, 19 Brangus
      three-way crosses and 15 Braunvieh three-way crosses, were genotyped for the
      CAPN4751 [AF_248054.2:g.6545C>T (GenBank accession AF248054.2)] and CAST/DdeI
      [AF_159246.1:g.2959A>G (GenBank accession AF159246.1)] polymorphisms and
      phenotyped for Ribeye Area, Backfat Thickness, Intramuscular Fat, Shear Force
      (SF) and Myofibrillar Fragmentation Index (MFI). In relation to the CAPN4751
      polymorphism, a frequency of 10.5% was observed for the C allele in the Nellore
      breed. In the total sample of studied animals, a significant association was
      found between genotypes and meat tenderness, assessed by SF (P = 0.005) and MFI
      (P = 0.008), with genotype CT being more favourable than TT. For the CAST/DdeI
      polymorphism, a frequency of 55.7% was found for the A allele in the Nellore
      breed. In the total sample, a significant association was observed between
      genotypes and meat tenderness - SF (P = 0.004) and MFI (P = 0.006), with genotype
      AA being more favourable than AG. The relationship between genotypes and aged
      meat tenderness in confluence with the distribution of favourable alleles shows
      great potential for application of the CAPN4751 and CAST/DdeI polymorphisms in
      the genetic improvement of the Nellore breed, whilst contributing to the
      validation, in this breed and in its crosses with B. taurus, of the association
      results previously described in the literature.

PMID- 19392829
TI  - The indel polymorphisms of the prion protein gene (PRNP ) in Chinese yak.

PMID- 19392830
TI  - Polymorphism of the pig acetyl-coenzyme A carboxylase alpha gene is associated
      with fatty acid composition in a Duroc commercial line.
AB  - Acetyl-coenzyme A carboxylase alpha (ACACA) catalyses the first committed step in
      the biosynthesis of long-chain fatty acids (FA) by converting acetyl-CoA into
      malonyl-CoA. In pigs, the ACACA gene maps to a chromosome 12 QTL with important
      effects on FA composition. In the present study, we have sequenced the coding
      region of the pig ACACA gene in 15 pigs, identifying 21 polymorphic sites that
      were either synonymous or non-coding. Ten of these SNPs segregated in a Duroc
      commercial population (n = 350) for which lipid metabolism and meat and carcass
      quality trait records were available. Significant associations were found between
      two linked single nucleotide polymorphisms (c.4899G>A and c.5196T>C) and
      percentages of carcass lean, intramuscular fat, monounsaturated, saturated
      (myristic, palmitic and stearic) and polyunsaturated (linoleic) FAs in the
      longissimus thoracis et lumborum muscle, along with serum HDL-cholesterol
      concentration. The most important allele substitution effects were observed for
      the polyunsaturated/saturated FA ratio (13-21% of the phenotypic mean) as well as
      for the percentages of omega-6 and polyunsaturated FAs, especially linoleic acid
      (7-16% of the phenotypic mean). These results suggest the existence of a causal
      mutation, mapping to the chromosomal region containing the pig ACACA gene, with
      marked effects on FA composition of meat.

PMID- 19392831
TI  - Early effects of Sertoli cell-selective androgen receptor ablation on testicular
      gene expression.
AB  - Evidence from several models of hormone depletion and/or replacement and from
      knockout animals points to a key role of androgens in the control of
      spermatogenesis. In testes of mice with a Sertoli cell-selective ablation of the
      androgen receptor (SCARKO), transcriptional profiling, using microarray
      technology, revealed that, already on postnatal day 10,692 genes are
      differentially expressed compared with testes of control mice. Further evaluation
      of a subset of these genes by quantitative RT-PCR suggested that differences in
      expression may already be evident on day 8 or earlier. As the androgen receptor
      in mouse Sertoli cells becomes immunologically detectable around day 5, we tried
      to identify the earliest responses to androgens by a new transcriptional
      profiling study on testes from 6-day-old SCARKO and control mice. No obvious and
      novel early androgen response genes, potentially acting as mediators of
      subsequent indirect androgen actions, could be identified. However, several genes
      differentially expressed on day 10 already displayed a response to androgen
      receptor ablation on day 6. Quantitative RT-PCR studies for 12 of these genes on
      10 paired SCARKO and control testes from 4-, 6-, 8-, 10-, 20- and 50-day-old mice
      revealed significant differences in expression level from day 4 onwards for three
      genes (Eppin, PCI, Cldn11) and from day 6 onwards for one more gene (Rhox5). For
      at least two of these genes (Rhox5 and Eppin), there is evidence for direct
      regulation via the androgen receptor. For three additional genes (Gpd1, Tubb3 and
      Tpd52l1) significantly lower expression in the SCARKO was noted from day 8
      onwards. For all the studied genes, an impressive increase in transcript levels
      was observed between day 4-50 and differential expression was maintained in
      adulthood. It is concluded that the SCARKO model indicates incipient androgen
      action in mouse Sertoli cells from day 4 onwards.

PMID- 19392832
TI  - The Mental Capacity Act 2005 Deprivation of Liberty Safeguards and people with
      dementia: the implications for social care regulation.
AB  - The Mental Capacity Act 2005 introduced legal safeguards (which came into force
      in April 2009) aimed at protecting the liberty of people lacking capacity
      admitted to institutions in England and Wales. This paper discusses the adequacy
      of the Deprivation of Liberty Safeguards for protecting the liberty of residents
      in social care settings and the role of regulation in monitoring their
      implementation. In particular, the potential impact of planned unitary regulation
      on the regulator's ability to protect residents' liberty is critiqued, centring
      on people with dementia living in care homes. It is suggested that the capacity
      of the safeguards to adequately protect the liberty of residents with dementia
      may be limited by under-recognition of the extent to which deprivation of liberty
      can actually occur in care homes, insufficient resourcing and a lack of critical
      independence in their proposed implementation. In addition, the planned
      contraction of regulation--especially a reduction in inspections--will constrain
      the regulator's ability to ensure that residents' right to liberty is protected.
      The author concludes that the new model of regulation adopted by the UK
      government has prioritised economic efficiency over safeguarding the right to
      liberty of vulnerable residents in institutions.

PMID- 19392834
TI  - Nomenclature for factors of the HLA system, December 2008 update*

PMID- 19392833
TI  - Health researchers' attitudes towards public involvement in health research.
AB  - OBJECTIVE: To investigate health researchers' attitudes to involving the public
      in research. BACKGROUND: Public involvement in research is encouraged by the
      Department of Health in the UK. Despite this, the number of health researchers
      actively involving the public in research appears to be limited. There is little
      research specifically addressing the attitudes of health researchers towards
      involving the public: how they interpret the policy, what motivates and de
      motivates them and what their experiences have been to date. DESIGN: A
      qualitative research design, using semi-structured telephone interviews. SETTING
      AND PARTICIPANTS: Fifteen purposively sampled UK-based University health
      researchers were the participants. Interviews were conducted over the telephone.
      FINDINGS: The participants suggested varying constructions of public involvement
      in research. Arguments based on moral and political principles and
      consequentialist arguments for involving the public in research were offered and
      most participants highlighted the potential benefits of involving the public.
      However, feelings of apprehension expressed by some participants imply that a
      number of researchers may still be uncomfortable with involving the public, as it
      presents a different way of working.

PMID- 19392835
TI  - The combination of polymorphisms within MCP-1 and IL-1beta associated with
      ulcerative colitis.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte
      recruitment to sites of inflammation. Raised level of MCP-1 has been widely
      demonstrated in the intestinal mucosa of patients with ulcerative colitis (UC),
      suggesting an important role of MCP-1 in the pathogenesis of UC. The -2518A/G
      polymorphism in the promoter region of MCP-1 gene affecting its transcriptional
      activation has been reported recently. In order to assess the potential role of
      this polymorphism in UC, we examined its distribution in 162 unrelated UC
      patients and 203 healthy controls. In addition, considering the gene regulatory
      association between interleukin-1beta (IL-1beta) and MCP-1, we further examined
      whether the gene polymorphisms between MCP-1 and IL-1beta exert synergetic
      effects on risk of UC. Our results show that the distribution of MCP-1 genotype
      or allele frequencies between UC patients and controls was not significantly
      different; however, the association between the polymorphism of MCP-1 -2518 GG
      and the polymorphism of IL-1beta-511 T in UC patients is significant (OR 2.062,
      95% CI 1.034-4.113, P = 0.038). This is the first report describing the
      association between MCP-1 polymorphism and UC, and our data suggest that the MCP
      1 -2518 polymorphism itself does not represent an independent genetic risk factor
      for UC. In contrast, the combination polymorphisms between MCP-1 and IL-1beta can
      increase UC risk significantly, which might help us understand the molecular
      mechanism underlying the development of UC.

PMID- 19392836
TI  - Haplotype analysis of HLA-A, -B antigens and -DRB1 alleles in south Indian HIV-1
      infected patients with and without pulmonary tuberculosis.
AB  - We have shown earlier the association of human leucocyte antigen (HLA)-A11 with
      resistance and HLA-B40 and -DR2 with susceptibility to HIV and HIV-TB. In the
      present study, we have attempted to find out the HLA-DR2 subtypes and the
      possible HLA-A/-B/-DRB1 haplotype combinations that are associated with
      susceptibility or resistance to HIV and HIV with pulmonary tuberculosis
      (HIV+PTB+). HLA-DR2 subtyping was carried out by polymerase chain reaction-based
      sequence-specific oligonucleotide probe method. Overrepresentation of HLA
      DRB1*1501 in HIV-positive PTB-negative (HIV+PTB-) patients (P = 0.004, P(c) =
      0.06) and -DRB1*1502 in HIV-positive PTB-positive (HIV+PTB+) patients (P = 0.019)
      was observed as compared to healthy controls. Haplotype analysis revealed an
      increased frequency of HLA-A2-DRB1*1501 haplotype in HIV+PTB- patients (P =
      0.008) and HLA-A2-DRB1*1502 among HIV+PTB+ patients (P = 0.01) compared to
      healthy controls. The haplotypes B40-DRB1*1501 and B40-DRB1*04 were found to be
      moderately increased in HIV+PTB(-) and HIV+PTB+ patients (P < 0.05). The study
      suggests that HLA-A2-DRB1*1501 haplotype may be associated with HIV infection
      while HLA-A2-DRB1*1502 haplotype might be associated with susceptibility to PTB
      in HIV patients. Moreover, HLA-B40-DRB1*1501 and HLA-B40-DRB1*04 haplotypes may
      be associated with susceptibility to HIV infection and to PTB in HIV patients.

PMID- 19392837
TI  - Impact of ageing and drug consumption on oral health.
AB  - The impact of ageing on oral health and salivary flow is usually over-estimated
      possibly because of the high frequency of polypharmacy observed in this subset of
      patients. Understanding the physiological changes and treatment-related oral
      complications of older patients is essential to promote accurate management of
      symptoms and improve their quality of life. The current paper reviews age-related
      physiological chances in salivary glands and the effect of polypharmacy on oral
      health, focusing on xerostomia and hyposalivation.

PMID- 19392838
TI  - Resting myocardial velocity gradient is a reliable measurement that identifies
      viable myocardium.
AB  - In the setting of coronary artery disease, two-thirds of LV dysfunction is not
      the result of irreversible scar, but rather caused by impairment in function and
      energy use of "still-viable" myocyte. The opportunity for improved function, if
      coronary blood flow is restored, is there which makes the identification of
      viable myocardium important. PURPOSE: The purpose of this study is to identify
      the value of resting myocardial velocity gradient (MVG) in detecting viable
      myocardium in patients with healed anterior wall myocardial infarction (MI).
      PATIENTS AND METHODS: The study included 30 patients with healed anterior MI, who
      were submitted to conventional echocardiography and tissue Doppler for
      measurement of MVG. Myocardial perfusion scan using Technetium (Tc)-99m was the
      gold standard test for the detection of viability. Ten healthy control subjects
      were also included to obtain reference values for MVG. RESULTS: Resting MVG was
      able to differentiate infarct regions, and to detect viable myocardium compared
      to Tc-99m studies (0.68 +/- 0.2 vs 0.49 +/- 0.22) P < 0.01. CONCLUSION: MVG
      provides quantitative assessment of the regional wall thickening that help
      localizing the infarct zone and detecting viable myocardium at rest.

PMID- 19392839
TI  - Reduced peak atrial systolic mitral annular velocity predicts the development of
      nonvalvular atrial fibrillation.
AB  - We investigated whether the echocardiographic parameters of the left atrium (LA)
      can predict the development of nonvalvular atrial fibrillation (AF). Among 14,062
      patients (>20 years old) who underwent an echocardiographic examination were
      evaluated, 2,606 patients who underwent follow-up ECG with an interval of >6
      months were investigated. Newly developed AF was noted in 42 (1.6%) patients with
      follow-up duration of 31.8 +/- 8.9 months. Cox regression analysis revealed that
      a higher left atrial volume index (hazard ratio [HR]=1.06; 95% confidence
      interval [CI] 1.03-1.09, P < 0.001), relative wall thickness (RWT) of>or=0.407
      (HR=2.74, 95% CI 1.39-5.41, P=0.004), a reduced peak atrial systolic mitral
      annular velocity (HR=0.845, 95% CI 0.72-0.99, P=0.037), and an advanced age
      (HR=1.04, 95% CI 1.01-1.07, P=0.009) were independently related to the
      development of nonvalvular AF. Therefore, reduced A', which is parameter of LA
      contractile function, might be an important predictor for the development of
      nonvalvular AF.

PMID- 19392840
TI  - Diastolic function study with conventional and pulsed tissue Doppler
      echocardiography imaging in acromegalic patients.
AB  - Acromegaly is associated with myocardial hypertrophy and it can progress to
      diastolic and systolic dysfunction. PURPOSE: To evaluate diastolic function in
      acromegalic patients through conventional echocardiography (CD) and tissue
      Doppler imaging (TDI). METHODS: Seventeen acromegalic patients were submitted to
      CD and TDI, and early (E) and atriogenic (A) transmitral flow were evaluated in
      mitral, septal, and tricuspid regions. RESULTS: In comparison with controls the
      means of conventional (1.06), septal (1.01), and tricuspid (0.98) E/A ratio were
      significantly lower in acromegalic patients. E/A ratio <1.0 was demonstrated in
      41% and 49% of acromegalics by DC and TDI, respectively, with no statistical
      difference among the two methods. An inverse linear correlation was shown between
      mitral E/A ratio and acromegalic age (r =-0.7). CONCLUSION: In this study, DC and
      TDI were equally effective in demonstrating diastolic dysfunction, a common
      finding in acromegalic patients.

PMID- 19392841
TI  - Analysis of left ventricular regional dyssynchrony: comparison between real time
      3D echocardiography and tissue Doppler imaging.
AB  - BACKGROUND: There is a paucity of information concerning left ventricular (LV)
      dyssynchrony assessment by real time three-dimensional (3D) echocardiography
      (RT3DE) versus tissue Doppler imaging (TDI). AIMS: To compare RT3DE and TDI LV
      dyssynchrony assessment. METHODS: A prospective study of 92 individuals (56 men,
      age 47 +/- 10 years), 32 with dilated cardiomyopathy (CMP), and 60 healthy
      individuals. By RT3DE, we measured the LV% dyssynchrony index (DI) of 6, 12, and
      16 segments (SDI). By pulsed-wave TDI, we measured the QS electromechanical
      interval in the basal segments of the mitral valve annulus of the septum, the
      lateral, anterior and inferior walls, and the TDI% DI. RESULTS: In the normal
      group, the 3D DI was 1.1 +/- 0.8%, 1.4 +/- 1.3%, 1.8 +/- 1.7%, for 6 segments, 12
      segments, and SDI, respectively. The correlation coefficient (Pearson's r) for
      the TDI DI and SDI was r = 0.2381 (P = 0.0470). In CMP group, the 3D DI was 4.6
      +/- 5.4%, 7.9 +/- 7.1%, 11.1 +/- 7.1%, for 6 segments, 12 segments, and SDI,
      respectively. The correlation coefficient for TDI DI and SDI was r = 0.7838 (P <
      0.0001). CONCLUSIONS: We observed a good correlation between RT3DE and tissue
      Doppler LV dyssynchrony assessment in patients with advanced heart failure.

PMID- 19392842
TI  - Acute changes in cardiac synchrony and output according to RV pacing sites in
      Koreans with normal cardiac function.
AB  - INTRODUCTION: The synchrony of the pacing heart can be affected by the right
      ventricular (RV) pacing site and is crucial to cardiac function in pacemaker
      recipients. We evaluated the acute changes in cardiac synchrony according to the
      RV pacing sites in normal systolic functioning subjects with normal QRS. METHODS:
      We conducted this study with 30 patients with the pacing in the RV apex (RVA), RV
      septum (RVS), and RV outflow tract (RVOT) in a sequential manner. Transthoracic
      echocardiography was conducted at rest and during pacing in order to measure
      interventricular and intraventricular dyssynchrony in all patients. RESULTS: QRS
      duration (148.1 +/- 12.8 ms) of RVA pacing was significantly shorter than that of
      RVS pacing (154.4 +/- 14.1 ms, P < 0.01) and RVOT pacing (160.6 +/- 15.7 ms, P <
      0.001). We noted no statistically significant difference in cardiac output
      according to the pacing sites. The interventricular dyssynchrony with M-mode and
      Doppler echocardiography in RVOT pacing was increased to an insignificant degree
      as compared with those with RVS pacing or RVA pacing. The intraventricular
      dyssynchrony with tissue Doppler echocardiography in RVA pacing was reduced
      significantly as compared with that of RVS pacing or RVOT (RVA = 60.3 +/- 32.7
      ms, RVS = 82.1 +/- 33.8 ms, RVOT = 79.1 +/- 33.3 ms; RVA vs RVS = P < 0.05, RVA
      vs RVOT = P < 0.01, RVS vs RVOT = P = NS). CONCLUSION: RVA pacing is superior to
      RVS and RVOT pacing with regard to intraventricular synchrony in normal systolic
      functioning subjects with normal QRS. Cardiac output at RVA pacing is not
      inferior to other sites.

PMID- 19392843
TI  - Echocardiographic assessment of conjoined twins with congenital heart disease in
      Shanghai.
AB  - BACKGROUND: The aim of this study is to improve the diagnosis of congenital heart
      disease in conjoined twins using echocardiography. METHODS: Six sets of conjoined
      twins at Shanghai Children's Medical Center and Xin-Hua Hospital from 1980 to
      2006 were assessed retrospectively. Cardiac anomalies of varying degrees of
      severity were first evaluated using 2D echocardiography. Tissue Doppler imaging
      (TDI) was then performed if fused ventricles were suspected. Peak systolic
      velocities, peak systolic strain rates, and peak systolic strains at the fused
      myocardium were quantitatively measured using strain rate imaging (SRI). If the M
      mode echocardiographic image was poor or difficult to measure, the myocardial
      performance index (MPI) of the left ventricle was calculated. RESULTS:
      Intracardiac anomalies were diagnosed correctly using echocardiography and
      confirmed by surgical findings. Cardiac functional assessment using MPI
      demonstrated heart failure in three out of the eight individuals. Subtle
      conjunction of the ventricles, however, were more difficult to visualize and two
      sets of conjoined twins with fused hearts could not be clearly demonstrated by
      echocardiography. In one case of suspected ventricular wall conjunction, TDI
      showed separate ventricular myocardia which was confirmed at surgery.
      CONCLUSIONS: Intracardiac anomalies and ventricular function can be readily
      demonstrated by echocardiography, but subtle conjunction of the ventricles may be
      more difficult to visualize. TDI may be required if there is uncertainty about
      the degree of cardiac fusion.

PMID- 19392844
TI  - Salvage esophagectomy after definitive chemoradiotherapy for synchronous double
      cancers of the esophagus and head-and-neck.
AB  - Head-and-neck cancer is frequently associated with esophageal cancer. Because the
      operative procedures for these synchronous double cancers are too invasive,
      definitive chemoradiotherapy tends to be applied as an initial treatment. A
      salvage esophagectomy for either recurrent or residual disease after definitive
      chemoradiotherapy in patients with such double cancer has never been reported. We
      reviewed 21 patients with esophageal cancer who underwent a salvage esophagectomy
      after definitive chemoradiotherapy. Among them, the treatment course of five
      patients who underwent a salvage esophagectomy for patients with synchronous
      double cancers of the esophagus and head-and-neck region was analyzed. Because
      head-and-neck cancer was well controlled after chemoradiotherapy in all five
      patients, a salvage esophagectomy was indicated for either recurrent or residual
      esophageal cancer after definitive chemoradiotherapy. Anastomotic leakage
      developed in four patients; however, no other complications including pulmonary
      complications were recognized. All of them were discharged to home and three of
      them are still alive without any recurrence for 20-43 months. A salvage
      esophagectomy should be considered as a treatment option for either recurrent or
      residual esophageal cancer with well-controlled head-and-neck cancer after
      definitive chemoradiotherapy when complete resection of the esophagus is
      expected.

PMID- 19392845
TI  - Drug-induced esophagitis.
AB  - Drug-induced esophagitis is being recognized increasingly in the past few years.
      Since 1970 more than 650 cases have been reported worldwide caused by 30 or more
      medications. We have reviewed these cases with a view to classifying this disease
      based on underlying pathological mechanism. Drug-induced esophageal injury tends
      to occur at the anatomical site of narrowing, with the middle third behind the
      left atrium predominating (75.6%). The disease is broadly classified into two
      groups. The first group being transient and self-limiting as exemplified by the
      tetracycline group induced injury (65.8%). The second is the persistent
      esophagitis group, often with stricture, with two distinct entities: (i) patients
      on nonsteroidal anti-inflammatory agents whose injury is aggravated by
      gastroesophageal reflux (21.8%) (reflux aggravated); and (ii) patients with
      potasium chloride and quinidine sulphate induced injury (12.4%) (persistent drug
      injury). Severe esophageal injury has been reported in some women taking
      biphosphonates as treatment for postmenopausal osteoporosis. Endoscopic findings
      in such patients with esophageal injury generally suggested a chemical
      esophagitis, with erosions or ulcerations and exudative inflammation accompanied
      by thickening of the esophageal wall. Most cases of medication-induced esophageal
      injury heal without intervention within a few days. Thus, the most important
      aspect of therapy is to make the correct diagnosis and then to avoid reinjury
      with the drug. When possible, potentially caustic oral medications should be
      discontinued.

PMID- 19392846
TI  - The number of lymph node metastases influences survival and International Union
      Against Cancer tumor-node-metastasis classification for esophageal squamous cell
      carcinoma.
AB  - To study the influence of the number of metastatic lymph nodes (LNs) on survival
      and International Union Against Cancer tumor-node-metastasis (TNM) classification
      for esophageal carcinoma. The clinicopathological data on 1146 patients with
      esophageal squamous cell carcinoma who had undergone an esophagectomy were
      retrospectively studied. Survival was analyzed by the Kaplan-Meier method. By
      subclassifying the nodes (N) category according to the number of metastatic LNs
      as: N0 for no LN metastases; N1(1) for only one positive node; and N1(2) for
      >or=2 positive nodes. TNM staging was refined as stage IIa (T2-3N0M0), stage IIb
      (T1N1M0 and T2N1(1)M0), stage IIIa (T2N1(2)M0 and T3N1(1)M0), and stage IIIb
      (T3N1(2)M0 and T4NanyM0), and the survival was analyzed. LN metastases was found
      in 380 of 1146 (33.2%) treated esophageal cancer patients. In 4270 LNs harvested,
      metastases was detected in 807 (18.9%). The 5-year survival rates of the patients
      with 0, 1, and >or=2 positive nodes were 59.8, 33.4, and 9.4%, respectively.
      There was statistically significant difference among these three groups. The 5
      year survival of the patients in stages T2N1M0 and T3N1M0 was significantly
      higher in the N1(1) group than in the N1(2) group (41.5 vs 24.1%, and 31.2 vs
      6.8%, P<0.001). The 5-year survival rates of the patients in refined stage IIa,
      IIb, IIIa, and IIIb were 57.1, 42.2, 28.6, and 8.5%, with significant difference
      existing in each stage groups. The number of positive LNs significantly
      influenced survival of the patients with esophageal cancer. Three grade
      classification (0, 1, >or=2 positive nodes) could quite well demonstrate the
      effect of the number of LN metastases and the survival. The refined TNM
      classification based on the number of LN metastases could better reflect the
      prognosis of esophageal cancer. Our results offer a strong rationale for refining
      the International Union Against Cancer TNM classification for esophageal
      carcinoma.

PMID- 19392847
TI  - Systematic approach of postoperative gastric conduit complications after
      esophageal resection.
AB  - Complications after esophagectomy related to ischemia of the graft are dreaded.
      Prompt assessment of the situation is essential. The series presented describes
      our experience regarding the evaluation of gastric tube complications. A score is
      presented classifying flexible endoscopy and CT-scan findings. A retrospective
      analysis from the charts of 47 consecutive patients who underwent esophagectomy
      for cancer was conducted. Patients who underwent upper endoscopy during
      admittance were entered in this study. Findings on flexible endoscopy and CT scan
      were systematic scored. According to the findings, different attitudes were
      taken. Between January 2006 and December 2007, 47 patients underwent
      esophagectomy for cancer. Eleven (23%) out of 47 patients were suspected to have
      complications related to the viability of the anastomosis. Median period to
      deterioration was 5 days. In 3 (27%) patients, stent placement was the only
      intervention necessary. In 2 (18%) patients, stent placement was combined with
      drainage of abscesses in the upper mediastinum. Five (46%) patients required a
      new right thoracotomy, with drainage of mediastinal abscesses and empyema. In 2
      patients a limited resection and a new cervical anastomosis with a stent was
      created. Mean intensive care admission and hospital admittance was 30.2 days and
      67.9 days, respectively. Two patients (18%) died during hospital admittance. All
      cervical anastomosis required postoperative dilatation. No complications related
      to the use of flexible endoscopy were seen. An aggressive policy is adopted in
      patients deteriorating following esophagectomy. CT-scanning of the thorax and a
      flexible endoscopy of the gastric conduit should always be performed. Direct
      therapy should be adopted without delay.

PMID- 19392848
TI  - Building a bioresource for esophageal research: lessons from the early experience
      of an academic medical center.
AB  - The establishment of biorepositories, linked to clinical and epidemiologic data,
      are central to the goals of personalized medicine and individualized cancer
      therapy. Repositories of DNA, RNA, and serum samples are valuable resources for
      cancer research, enabling the investigation of the underlying causes of cancer
      development, progression, and prognosis, as well as providing a resource for the
      investigation of biomarkers for early detection and prediction of response. With
      a greater reliance on sample-derived data for molecular-based research and
      clinical care, improved standards and informatics for sample procurement,
      storage, and analysis are necessary to maximize the value of tissue collection
      for research participants, investigators, and academic medical centers. We
      present herein the experience of an academic medical center in establishing a
      repository for esophageal research, with discussion of elements to be considered
      when establishing such a resource, from the quality assurance of samples to the
      organized collection and storage of associated clinical data. The development of
      this biorepository required significant planning to identify and consent
      participants by dedicated clinical and research personnel. Ensuring the quality
      of any biobank is of utmost importance, and one must understand the sample
      variability that exists during the acquisition of biospecimens. The time and type
      of fixative have been optimized in our unit by standard operating protocols.
      Methods for biomolecule extraction were tested by examining both the quality and
      the quantity of recovered sample. These procedures were overseen by a designated
      biobank manager, responsible for the acquisition of the sample from surgery,
      which limits variability in sample collection. Our unit also has a dedicated
      database manager for the maintenance of quality clinical data linked to the
      bioresource. The development and expansion of such repositories, at local and
      national levels, is required to enable leading academic medical centers and their
      investigators to provide optimal and molecularly guided care to their patients.

PMID- 19392849
TI  - Entrapment of a nasopharyngeal temperature probe: an unusual complication during
      an apparently uneventful elective revision laparoscopic Nissen fundoplication.
AB  - We report the first case of nasopharyngeal temperature probe entrapment during an
      apparently uneventful elective revision laparoscopic Nissen fundoplication that
      precipitated a continuous quality improvement project at our institution. We
      describe changes in our clinical practice that resulted from this occurrence and
      envision these modifications will have a positive influence on patient care.

PMID- 19392850
TI  - The association between body mass index and Barrett's esophagus: a systematic
      review.
AB  - Biological plausibility and evidence from case series indicate that an increased
      body mass index could be a risk factor for Barrett's esophagus. The aim of this
      study was to assemble and appraise the available evidence on the association of
      body mass index and Barrett's esophagus in a narrative approach. A systematic
      literature review identified a nested case-control study and 10 case-control
      studies, with sample sizes of between 129 and 953. Overall, cases were on average
      older than controls, more often male and white, but did not differ with regards
      to body mass index. An increased body mass index (> or =30 and > or =35 kg/m(2))
      was associated with greater risk of Barrett's esophagus in four studies (odds
      ratio range: 2.0-4.0). These studies, however, did not adjust for symptoms
      suggestive of gastroesophageal reflux disease. No significant association was
      reported in the other six studies. To conclude, the existing evidence on the
      association between body mass index and risk of Barrett's esophagus relates
      primarily to case-control studies and is inconsistent. Gastroesophageal reflux
      symptoms can be a potential confounder and further research should better address
      this issue. Evidence from cohort studies may help shed further light on this
      putative association, which is of relevance to public health and cancer control.

PMID- 19392851
TI  - Esophageal pH exposure and epithelial cell differentiation.
AB  - It is proposed that epithelial changes induced by gastroesophageal reflux disease
      are related to the pH environment of the esophageal lumen. We hypothesized that
      the various types of esophageal epithelium are associated with specific pH
      environments that induce their formation. The aim of this study was to compare
      the luminal pH environment to the histology of the distal esophageal epithelium
      in patients with gastroesophageal reflux disease. A total of 197 symptomatic
      patients with increased esophageal acid exposure on 24-hour pH monitoring were
      grouped according to the histology based on biopsies from the distal esophagus:
      17 with squamous epithelium, 126 with cardiac epithelium (CE), and 54 with
      Barrett's epithelium (BE). All were free of Helicobacter pylori infection and
      monitored off acid suppression therapy. Acid exposure was expressed as the
      percent of time the luminal pH was at intervals of 0-1, 1-2, 2-3, 3-4, 4-5, 5-6,
      and 6-7 over a 24-hour period. Patients with BE spent significantly more time at
      pH intervals 2-3, 3-4, and 4-5 than those with CE. This pattern switched at pH
      interval 5-6, where patients with cardiac mucosa spent more time than those with
      BE. Patients with squamous and CE had similar pH exposure at all intervals.
      Patients with BE have significantly longer exposure time at the pH interval of 2
      to 5 compared to those with cardiac and squamous epithelium. This suggests that
      the exposure of stem cells to a luminal pH between 2 and 5 may trigger the
      differentiation of CE into intestinalized CE.

PMID- 19392852
TI  - Polymorphisms of HLA-A and HLA-B genes in genetic susceptibility to esophageal
      carcinoma in Chaoshan Han Chinese.
AB  - Esophageal carcinoma (EC) occurs at high rate in Chaoshan region of southern
      China. Human leukocyte antigen (HLA) polymorphism has been implicated in risk for
      various cancers. To investigate the impact of HLA-A and HLA-B polymorphisms on
      susceptibility to EC, a case-control study was conducted among 206 patients with
      esophageal squamous cell carcinoma and 524 controls from Chaoshan Han population.
      HLA-A and HLA-B polymorphisms were genotyped by polymerase chain reaction
      sequence-specific primers. Genotypic association tests for dominant, recessive,
      and additive models, and haplotypic association were calculated using
      unconditional logistic regression. A*11 was identified in a recessive model as an
      only allele strongly associated with EC risk (odds ratios [OR]=2.10, 95%
      confidence interval [CI]=1.33-3.31) even after correction for multiple test. The
      haplotypes A*02-B*46 (OR=1.53, 95% CI=1.04-2.24) and A*11-B*51 (OR=2.29, 95%
      CI=1.20-4.40) showed association with increased risk for EC, whereas A*11-B*58
      (OR=0.00, 95% CI=0.00-0.82) was associated with decreased risk, though the
      significance of these haplotypes was lost after correction. This is a first
      association study at genetic level identifying HLA-A and HLA-B-related variations
      in genetic susceptibility to EC among Chaoshan population. The variation pattern
      is likely to be EC-specific because it is different from that observed for
      nasopharyngeal carcinoma in the same study population and might, at least in
      part, explain the high rate of EC in this ethnic group.

PMID- 19392853
TI  - Prognostic significance of perigastric lymph nodes metastases on survival in
      patients with thoracic esophageal cancer.
AB  - Several publications have showed that the number of metastatic lymph node (LN)
      should be taken into consideration in nodal category of esophageal cancer, but
      seldom considered extent of involved regional LNs. The aim of this study is to
      evaluate the significance of the extent of regional LN metastasis on survival in
      patients with esophageal cancer. A total of 245 thoracic esophageal cancer
      patients underwent transthoracic esophagectomy with standard lymphadenectomy
      between January 2000 and December 2006 were included in the study. Data including
      demographic factors, pathologic findings, LN parameters and survival outcomes
      were collected. The survival experience was depicted using Kaplan-Meier method. A
      multivariate Cox proportional hazard model was used to screen the significant
      prognostic factors. The univariate analysis to further explore the significant
      prognostic factor was done by log-rank test. After a median follow-up of 53.2
      months, the 5-year survival rate was 46.3% for the entire cohort. Cox model
      regression indicated that the LN status and perigastric nodal status, aside from
      residual tumor status, histological tumor type and depth of invasion, were the
      independent prognostic factors. Patients without LN metastasis had better 5-year
      survival than those with positive nodes (64.2% vs. 18.9%, X2=35.875, P<0.001).
      However, For those patients with nodal involvement, there was no difference in 5
      year survival between patients with involved nodes<3 and >or=3 (27.8% vs. 0%,
      X2=0.925, P=0.336). When considering the location of LN metastasis, patients
      could be further stratified according to whether the perigastric nodes were
      involved or not (37.5% vs. 10.0%, X2=4.295, P=0.038). In conclusion, involved LN
      number had no prognostic implication in nodal involved patients based on our
      data. Whereas, perigastric nodal involvement should be used to refine the N
      category (N0, no nodal metastasis, N1, non-perigastric node metastasis, N2,
      perigastric node metastasis) for the future esophageal cancer staging criteria.

PMID- 19392854
TI  - Application of a modified McKeown procedure (thoracoscopic esophageal
      mobilization three-incision esophagectomy) in esophageal cancer surgery: initial
      experience with 30 cases.
AB  - Early efforts with minimally invasive esophagectomy (MIE) were hybrid approaches.
      No conclusive benefit was seen with this approach compared with the standard open
      procedure. Total MIE has demonstrated its advantages in single institution
      series. The drawbacks of total MIE include the steep learning curve and the high
      cost of the disposable instrumentation. We sought to determine the feasibility of
      modifying the surgical technique involved in the hybrid approach in an effort to
      decrease the cost of the surgery without compromising the outcome. From December
      2007 to September 2008, the modified McKeown procedure (thoracoscopic esophageal
      mobilization three-incision esophagectomy) was performed in 30 cases. The median
      operative time was 225 minutes (range, 195 -290 minutes) and the median average
      time of VATS was 70 minutes (range, 50 -130 minutes). Median lymph node retrieval
      was 25.6 +/- 4.8 nodes (15.1 +/- 3.4 intrathoracic) per patient. The median
      postoperative hospital stay was 17.1 +/- 6.3 days. There was no in-hospital (30
      days) mortality. Postoperative complications occurred in 9 patients (30%),
      including 2 (6.7%) pneumonia, 1 (3.3%) chylothorax, 1 (3.3%) delayed gastric
      emptying, 1 (3.3%) vocal cord palsy, 2 (6.7%) neck anastomotic leaks, and 2
      (6.7%) arrhythmias. This procedure is technically feasible and safe with lower
      mortality and mobility. The short-term surgical outcomes are comparable with most
      of the total MIE reports. Performing the gastric mobilization and spontaneous
      neck anastomosis first greatly facilitate and simplifies the VATS maneuver.

PMID- 19392855
TI  - Traumatic interface oedema two years after LASIK.

PMID- 19392856
TI  - Histological findings following the use of a space-making device for bone
      reformation and implant integration in the maxillary sinus of primates.
AB  - BACKGROUND: Previous studies have shown that membrane elevation results in
      predictable bone formation in the maxillary sinus provided that implants can be
      placed as tent poles. In situations with an extremely thin residual crest which
      impairs implant placement, it is possible that a space-making device can be used
      under the sinus membrane to promote bone formation prior to placement of
      implants. PURPOSE: The present study was conducted to test the hypothesis that
      the use of a space-making device for elevation of the sinus membrane will result
      in predictable bone formation at the maxillary sinus floor to allow placement of
      dental implants. MATERIALS AND METHODS: Eight tufted capuchin primates underwent
      bilateral sinus membrane elevation surgery, and a bioresorbable space-making
      device, about 6 mm wide and 6 mm in height, was placed below the elevated
      membrane on the sinus floor. An oxidized implant (Nobel Biocare AB, Gothenburg,
      Sweden) was installed in the residual bone protruding into the created space at
      one side while the other side was left without an implant. Four animals were
      sacrificed after 6 months of healing. The remaining four animals received a
      second implant in the side with a space-making device only and followed for
      another 3 months before sacrifice. Implant stability was assessed through
      resonance frequency analysis (RFA) using the Osstell (Osstell AB, Gothenburg,
      Sweden) at installation, 6 months and 9 months after the first surgery. The bone
      implant contact (BIC) and bone area inside the threads (BA) were histometrically
      evaluated in ground sections. RESULTS: Histologically there were only minor or no
      signs of bone formation in the sites with a space-making device only. Sites with
      simultaneous implant placement showed bone formation along the implant surface.
      Sites with delayed implant placement showed minor or no bone formation and/or
      formation of a dense fibrous tissue along the apical part of the implant surface.
      In the latter group the apical part of the implant was not covered with the
      membrane but protruded into the sinus cavity. CONCLUSIONS: The use of a space
      making device, with the design used in the present study, does not result in bone
      formation at the sinus floor. However, membrane elevation and simultaneous
      placement of the device and an implant does result in bone formation at the
      implant surface while sites with implants placed 6 months after membrane
      elevation show only small amounts of bone formation. It is suggested that lack of
      stabilization of the device and/or a too extensive elevation of the membrane may
      explain the results.

PMID- 19392858
TI  - Clinical trial: benefits and risks of immunomodulators and maintenance infliximab
      for IBD-subgroup analyses across four randomized trials.
AB  - BACKGROUND: Benefits and risks of concomitant immunomodulators and maintenance
      infliximab in inflammatory bowel disease (IBD) patients have not been adequately
      evaluated. AIM: To assess the effect of concomitant immunomodulator and
      infliximab maintenance therapy using data from four prospective, randomized Phase
      3 trials in IBD patients. METHODS: Overall, 1383 patients from ACCENT I and
      ACCENT II [luminal and fistulizing Crohn's disease trials] and ACT 1 and ACT 2
      [ulcerative colitis trials] were analysed. Patients were treated with placebo or
      infliximab 5 or 10 mg/kg at weeks 0, 2 and 6 followed by every-8-week maintenance
      therapy. Clinical response, clinical remission, fistula response, complete
      fistula response, infection and infusion reaction rates; serum infliximab
      concentrations and immunogenicity were summarized by baseline concomitant
      immunomodulator subgroup (use or non-use). RESULTS: Overall, almost 40% of
      evaluated IBD patients received concomitant immunomodulators. Efficacy,
      infection, and serious infection rates were generally similar in patients who
      received maintenance therapy with or without concomitant immunomodulators. There
      were no consistent differences in serum infliximab concentrations with or without
      immunomodulators in patients who received scheduled maintenance therapy.
      Concomitant immunomodulators reduced infusion reactions and immunogenicity.
      CONCLUSION: Concomitant immunomodulators did not improve efficacy or
      pharmacokinetics in IBD patients who received maintenance infliximab.

PMID- 19392857
TI  - A prospective study examining the effects of gender and sexual/physical abuse on
      mood outcomes in patients with co-occurring bipolar I and substance use
      disorders.
AB  - OBJECTIVES: Prior research suggests possible gender differences in the
      longitudinal course of bipolar disorder. This study prospectively examined gender
      differences in mood outcomes and tested the effects of sexual/physical abuse and
      posttraumatic stress disorder (PTSD). METHODS: Participants (49 men, 41 women)
      with co-occurring bipolar I and substance use disorders (92% alcohol, 42% drug)
      were enrolled in a group treatment trial. They were followed for eight months,
      with monthly assessments, yielding 32 weeks of data. Primary outcome measures
      were number of weeks in each mood state, recurrences of depression or mania, and
      polarity shifts from depression to mania or vice versa. Negative binomial
      regression was used to examine the effects of gender, lifetime abuse, and PTSD on
      these outcomes. RESULTS: Participants met syndromal criteria for a mood episode
      on a mean of 27% of 32 weeks, with depression occurring most frequently. Compared
      to men, women reported significantly more weeks of mixed mania [relative rate
      (RR) = 8.53], fewer weeks of euthymia (RR = 0.58), more recurrences of mania (RR
      = 1.96), and more direct polarity shifts (RR = 1.49) (all p < 0.05). Women also
      reported significantly higher rates of lifetime sexual or physical abuse (68%
      versus 33%), which partially explained the relationships between gender and mixed
      mania and direct polarity shifts. CONCLUSIONS: Participants experienced
      persistent mood symptoms over time. Women consistently reported poorer mood
      outcomes, and lifetime abuse may help explain observed gender differences in mood
      outcomes. Further research is necessary to better understand the treatment
      implications of these findings.

PMID- 19392859
TI  - Faecal DNA and calprotectin as biomarkers of acute intestinal toxicity in
      patients undergoing pelvic radiotherapy.
AB  - BACKGROUND: Acute intestinal toxicity is a frequent complication that may lead to
      interruption of treatment in patients undergoing pelvic radiotherapy. Reliable,
      non-invasive biological markers to evidence their severity are not yet available.
      AIM: To test faecal DNA and calprotectin as potential biomarkers of intestinal
      toxicity caused by pelvic radiotherapy. METHODS: Patients were categorized
      according to the location of the cancer as nonrectal (n = 25) and rectal (n =
      27). Four stool samples were collected at weeks w0, w3, w5 (end of radiotherapy)
      and w7. Faecal DNA was determined by quantitative PCR and calprotectin by ELISA.
      Intestinal toxicity was scored according to the Common Toxicity Criteria.
      RESULTS: In the nonrectal group, acute diarrhoea toxicity was present in 80% of
      patients, faecal DNA increased 10-fold during radiotherapy (1.5 x 10(3) copies/mg
      dry weight, 9.5 x 10(2)-8.8 x 10(3) at w0, median and interquartile range vs. 1.3
      x 10(4), 1.9 x 10(3)-3.9 x 10(4) at w5, P < 0.01), but was not recovered at w7
      (3.4 x 10(3), 1.5 x 10(3)-4.1 x 10(4)) and calprotectin doubled during treatment
      at w3 and w5. No significant changes in faecal markers were found in the rectal
      group. CONCLUSION: Faecal excretion of human DNA and calprotectin increased
      during pelvic radiotherapy treatment, and may be a good objective biomarker of
      intestinal damage in nonrectal cancer patients.

PMID- 19392860
TI  - Comparison of the prevalence of fructose and lactose malabsorption across chronic
      intestinal disorders.
AB  - BACKGROUND: Fructose malabsorption, lactose malabsorption and an early rise in
      breath hydrogen after lactulose (ERBHAL) may play roles in induction of symptoms
      in gastrointestinal conditions. AIM: To compare prevalence and interactions of
      fructose malabsorption, lactose malabsorption and ERBHAL among healthy subjects
      and those with chronic intestinal disorders using consistent breath hydrogen
      testing methodologies. METHODS: Consecutive series of Caucasian patients with
      Crohn's disease (n = 91), ulcerative colitis (56), functional gastrointestinal
      disorders (FGID) (201), coeliac disease (136) and 71 healthy volunteers underwent
      breath hydrogen testing using lactulose, fructose and lactose. RESULTS: Early
      rise in breath hydrogen after lactulose occurred more commonly in healthy
      controls (39%) than in Crohn's disease (20%) and untreated coeliac disease (14%;
      P < 0.008), but not FGID (27%), ulcerative colitis (26%) or treated coeliac
      disease (29%). Fructose malabsorption was more frequent in Crohn's disease (61%)
      than other groups (33-44%, P < 0.05). Lactose malabsorption was most common in
      Crohn's disease (42%) and ulcerative colitis (40%) and uncommon (10%) in 79
      patients with newly diagnosed coeliac disease. In Crohn's disease, concurrent
      Fructose malabsorption and lactose malabsorption was most common (29%), and the
      association of fructose malabsorption with ERBHAL seen overall (62%) was not
      observed (36%, P < 0.0001). CONCLUSIONS: Carbohydrate malabsorption and ERBHAL
      are normal physiological phenomena. The abnormal patterns observed in Crohn's
      disease may have pathogenic importance.

PMID- 19392861
TI  - Transcatheter arterial chemoembolization vs. chemoinfusion for unresectable
      hepatocellular carcinoma in patients with major portal vein thrombosis.
AB  - BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been limited in
      palliative treatment of unresectable hepatocellular carcinoma (HCC) with major
      portal vein (PV) invasion due to the possibility of liver failure following
      embolization. Transcatheter arterial chemoinfusion (TACI) has been an option in
      such cases. AIM: To compare clinical outcomes after TACE vs. TACI in HCC patients
      with major PV occlusion. METHODS: We compared clinical outcomes after TACE vs.
      TACI in HCC patients with major PV occlusion. From 2005 to 2007, 110 HCC patients
      with major PV thrombosis were treated with TACE (n = 49) or TACI (n = 61).
      RESULTS: The morbidity rate was similar for both TACE (6.1%) and TACI (6.5%)
      patients, and complications were adequately managed using medical treatment. The
      Kaplan-Meier survival analysis showed that the survival period was significantly
      longer for the TACE group (median: 14.9 months) than for the TACI (median: 4.4
      months) group (P < 0.001). There was a higher probability of death in the TACI
      group than in the TACE group in both our multivariate Cox-proportional hazards
      (OR 3.09, P < 0.001) and the propensity score-matched (27 pairs) cohort analyses
      (OR 2.27, P = 0.024). CONCLUSIONS: Transcatheter arterial chemoembolization can
      be safely performed in HCC patients with main PV occlusion. Compared with TACI,
      TACE may result in longer survival of HCC patients with major PV occlusion.

PMID- 19392862
TI  - Early identification of haemodynamic response to pharmacotherapy is essential for
      primary prophylaxis of variceal bleeding in patients with 'high-risk' varices.
AB  - BACKGROUND: A beta-blocker is recommended for primary prophylaxis of variceal
      bleeding; however, only one-third have hepatic venous pressure gradient (HVPG)
      response. The role of addition of isosorbide-5-mononitrate (ISMN) to beta-blocker
      and benefits of HVPG-guided 'a la carte' approach remain unclear. AIM: To
      determine the benefits of HVPG-guided pharmacotherapy in primary prophylaxis of
      variceal bleeding using beta-blocker and ISMN. PATIENTS AND METHODS: Consecutive
      patients of cirrhosis, with high-risk varices, with no previous variceal bleeding
      were included. After baseline HVPG, patients received incremental propranolol to
      achieve HR of 55/min. After one-month, HVPG was repeated to determine response
      (<12 mmHg or >or=20% reduction). ISMN was added in nonresponders and HVPG
      repeated. Patients were followed up for 24 months. RESULTS: Of 56 patients (age
      47 +/- 13, males 79%) from 89 eligible patients, 21 (38%) responded to beta
      blocker alone. Six additional patients responded to combination. Thus, overall
      48% (27/56) patients responded. Variceal bleeding occurred in seven of 56 (13%)
      patients [one of 27 (4%) responder, five of 23 (22%) nonresponders and one of six
      (17%) with unknown response; P = N.S.]. The actuarial probability of variceal
      bleeding at median 24 months was 4% in responders and 22% in nonresponders (P <
      0.05). Ten (18%) patients developed adverse effects to propranolol and six of 35
      (17%) to nitrates requiring dose reduction. Risk factors of variceal bleed were
      grade IV varices and haemodynamic nonresponse. CONCLUSIONS: For primary
      prophylaxis, a beta-blocker is effective in 38% and addition of ISMN raises the
      response rate to about half of patients. The HVPG-guided 'a la carte' approach
      may be considered for these patients.

PMID- 19392863
TI  - Meta-analysis: surveillance with ultrasound for early-stage hepatocellular
      carcinoma in patients with cirrhosis.
AB  - BACKGROUND: A majority of studies investigating the accuracy of ultrasound for
      detecting hepatocellular carcinoma (HCC) do not reflect how this test is used for
      surveillance vs. diagnosis. AIM: To determine the performance characteristics of
      surveillance with ultrasound for the detection of HCC, particularly early HCC as
      defined by the Milan criteria. METHODS: A systematic literature review using the
      MEDLINE and SCOPUS databases yielded six studies that evaluated the accuracy of
      ultrasound for HCC at any stage and 13 studies that were specific to early HCC.
      RESULTS: Surveillance ultrasound detected the majority of tumours before they
      presented clinically, with a pooled sensitivity of 94%. However, ultrasound was
      less effective for detecting early HCC with a sensitivity of 63%. Alpha
      fetoprotein provided no additional benefit to ultrasound. Meta-regression
      analysis demonstrated a significantly higher sensitivity for early HCC with
      ultrasound every 6 months than with annual surveillance. Current studies have
      limitations such as verification bias and are of suboptimal quality. CONCLUSIONS:
      Surveillance with ultrasound demonstrates limited sensitivity for early HCC,
      although this may be improved by testing at 6-month intervals. Currently
      available evidence evaluating surveillance ultrasound has significant limitations
      and future studies are necessary to determine optimal surveillance methods for
      early HCC.

PMID- 19392864
TI  - Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on
      daytime and nighttime heartburn in patients with non-erosive reflux disease.
AB  - BACKGROUND: The proportion of patients who respond to proton pump inhibitor (PPI)
      therapy is about 20% lower in those with non-erosive reflux disease (NERD) than
      in those with erosive oesophagitis. AIM: To assess efficacy and safety of
      dexlansoprazole MR, a PPI using Dual Delayed Release technology, in NERD
      patients. METHODS: In this 4-week, double-blind, placebo-controlled study, 947
      NERD patients randomly received dexlansoprazole MR 30 mg, 60 mg or placebo once
      daily (QD). The percentages of 24-h heartburn-free days (primary) and nights
      without heartburn (secondary) were assessed from patients' daily diaries.
      Investigators also assessed symptoms. Patients completed validated quality of
      life and symptom severity questionnaires. RESULTS: Dexlansoprazole MR provided
      significantly greater median percentages of 24-h heartburn-free days (54.9% and
      50.0% for the 30- and 60-mg doses vs. 17.5% for placebo, P < 0.00001) and nights
      without heartburn (80.8% and 76.9% vs. 51.7%, P < 0.00001 vs. placebo).
      Dexlansoprazole MR also reduced symptom severity. Quality of life improvements in
      patients receiving dexlansoprazole MR were consistent with clinical efficacy
      endpoints. Percentages of patients experiencing treatment-emergent adverse events
      were similar among groups. CONCLUSIONS: Dexlansoprazole MR 30 and 60 mg were
      superior to placebo in providing 24-h heartburn-free days and nights in NERD
      patients. Treatment was well tolerated.

PMID- 19392865
TI  - Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in
      patients with chronic hepatitis C virus infection receiving anti-viral agents
      interferon-alpha and ribavirin.
AB  - BACKGROUND: Hepatitis C virus (HCV) co-opts very-low-density lipoprotein (VLDL)
      pathways for replication, secretion and entry into hepatocytes and associates
      with apolipoprotein B (apoB) in plasma. Each VLDL contains apoB-100 and variable
      amounts of apolipoproteins E and C, cholesterol and triglycerides. AIM: To
      determine whether baseline lipid levels predicted treatment outcome. METHODS:
      Retrospective analysis was performed of 250 chronic hepatitis C (CHC) patients
      who had received anti-viral agents interferon-alpha and ribavirin; 165 had a
      sustained virological response (SVR). Pre- and post-treatment nonfasting lipid
      profiles were measured and non-high-density lipoprotein (non-HDL) cholesterol
      (i.e. apoB-associated) was calculated. Binary logistic regression analysis
      assessed factors independently associated with treatment outcome. RESULTS: There
      was an independent association between higher apoB-associated cholesterol (non
      HDL-C) and increased odds of SVR (odds ratio 2.09, P = 0.042). In multivariate
      analysis, non-HDL-C was significantly lower in HCV genotype 3 (g3) than genotype
      1 (P = 0.007); this was reversible upon eradication of HCVg3 (pre-treatment non
      HDL-C = 2.8 mmol/L, SVR = 3.6 mmol/L, P < 0.001). CONCLUSIONS: Higher apoB
      associated cholesterol is positively associated with treatment outcome in CHC
      patients receiving anti-viral therapy, possibly due to competition between apoB
      containing lipoproteins and infectious low-density HCV lipo-viral particles for
      hepatocyte entry via shared lipoprotein receptors.

PMID- 19392866
TI  - Systematic review: the epidemiology and clinical features of travellers'
      diarrhoea.
AB  - BACKGROUND: Travellers' diarrhoea is the most common medical complaint among
      persons venturing into developing areas from industrialized regions. AIM: To
      review recent developments dealing with microbiological, clinical,
      pathophysiological and therapeutic aspects of travellers' diarrhoea. METHODS: The
      author's extensive file plus a review of publications listed in PubMed on January
      22, 2009 on the topic of travellers' diarrhoea were reviewed. RESULTS:
      Travellers' diarrhoea is largely caused by detectable and undetected bacterial
      enteropathogens, explaining the remarkable effectiveness of antibacterial agents
      in prophylaxis and therapy of the illness. A number of host genetic polymorphisms
      have been recently linked with susceptibility to travellers' diarrhoea. Novel
      antisecretory agents are being developed for treatment considering their
      physiological effects in acute diarrhoea. All travellers should be armed with one
      of three antibacterial drugs, ciprofloxacin, rifaximin or azithromycin, before
      their trips to use in self therapy should diarrhoea occur during travel.
      Loperamide may treat milder forms of travellers' diarrhoea and can be employed
      with antibacterial drugs. CONCLUSIONS: Diarrhoea will continue to plague
      international travellers to high-risk regions. More studies of the incidence
      rate, relative important of the various pathogens by geographical region of the
      world, host risk factors and optimal therapeutic approach are needed.

PMID- 19392867
TI  - Epidermoid anal cancer prognosis comparison among HIV+ and HIV- patients.
AB  - BACKGROUND: Previous studies suggest a poor prognosis of epidermoid anal cancer
      in HIV+ patients. AIM: To investigate the long-term outcome of epidermoid anal
      cancer in HIV+ and HIV- patients in the highly active antiretroviral treatment
      (HAART) era. METHODS: We included all patients with epidermoid anal cancer
      referred to six hospitals from 1998 to 2004. RESULTS: In all, 151 patients (44
      HIV+, 107 HIV-) were reviewed retrospectively for 27 (median of 16-44) months.
      HIV+ patients were male (100% vs. 27%, P < 0.001) and younger (45 vs. 62 years
      old, P < 0.001) than HIV- patients. No significant differences were observed in
      the tumour stage, pelvic radiotherapy dose or concomitant chemotherapy, according
      to the HIV status. After chemoradiotherapy, similar numbers of HIV+ and HIV-
      patients had grade III-IV toxicity. A complete response was obtained in 82% and
      75% (N.S.) of cases, respectively. The disease-free survival rates were 77% and
      67% (N.S.) and the overall survival rates were 85% and 84% (N.S.), respectively,
      after 3 years of follow-up. Duration of HIV infection, viral load and CD4 count
      had no effect on the survival rate of HIV+ patients with EAC. CONCLUSIONS: The
      clinical outcome of HIV+ patients with epidermoid anal cancer is similar to that
      of HIV- patients. Therefore, the same therapeutic guidelines should be applied to
      both populations.

PMID- 19392868
TI  - Sustained virological responses following standard anti-viral therapy in
      decompensated HCV-infected cirrhotic patients.
AB  - BACKGROUND: Little data is available about predictors of sustained virological
      response (SVR) during anti-viral therapy of patients with decompensated HCV
      cirrhosis. AIMS: To determine whether rapid and early virological responses (RVR
      and EVR) could predict SVR and help optimize treatment in these patients.
      METHODS: A total of 94 cirrhotics underwent treatment with peg-interferon alfa-2b
      (1.5 microg/kg weekly) and ribavirin (800/1200 mg daily) for 48 or 24 weeks for
      genotypes 1/4 or genotypes 2/3, respectively. RESULTS: Overall, SVR was achieved
      in 33 patients (35.1%), 16% with genotype 1/4 and 56.8% with genotype 2/3 (P <
      0.01). At treatment week 4, 34 patients had undetectable HCV-RNA, 10 with
      genotype 1/4 and 24 with genotype 2/3. Of RVR patients, 24 achieved SVR (70.5%),
      6 and 18 with genotypes 1 and non-1. At the multivariate analysis, only EVR,
      genotypes 2 and 3, and adherence to full course and dosage of therapy retained
      their independent predictive power, with corresponding ORs of 25.5 (95% CI 3.0
      217.3), 4.2 (95% CI 1.2-15.3) and 9.1 (95% CI 2.2-38.0), respectively.
      CONCLUSION: In decompensated cirrhotic patients, anti-viral therapy with current
      regimens is feasible and associated with an overall SVR rate of 35.1%. Treatment
      ought to be pursued among patients who attain an EVR, and maintain a full course
      and dosage of therapy.

PMID- 19392869
TI  - Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative
      colitis.
AB  - BACKGROUND: Debate exists regarding to whether thiopurine therapy is as effective
      in ulcerative colitis (UC) as it is in Crohn's disease. AIM: To review
      systematically the efficacy of azathioprine (AZA) and mercaptopurine (MP) in UC,
      and to conduct a meta-analysis of randomized clinical trials evaluating the
      efficacy of AZA/MP for the induction or maintenance of UC clinical remission.
      METHODS:  SELECTION OF STUDIES: Evaluating AZA/MP for induction and/or
      maintenance of clinical remission of UC. Randomized-controlled-trials comparing
      AZA/MP with placebo/5-aminosalicylates were included in the meta-analysis. SEARCH
      STRATEGY: Electronic and manual. Study quality: Independently assessed by two
      reviewers. DATA SYNTHESIS: By 'intention-to-treat'. RESULTS: Thirty noncontrolled
      studies (1632 patients) were included in the systematic review. Mean efficacy of
      AZA/MP was 65% for induction and 76% for maintenance of the remission. Seven
      controlled studies were included in the meta-analysis. (i) Induction of
      remission: four studies (89 AZA/MP-treated patients) showed mean efficacy of 73%
      vs. 64% in controls (OR = 1.59; 95% CI = 0.59-4.29). (ii) Maintenance of
      remission: six studies (124 AZA/MP-treated patients) showed mean efficacy of 60%
      vs. 37% in controls (OR = 2.56; 95% CI = 1.51-4.34). When only studies comparing
      AZA/MP vs. placebo were considered, OR was 2.59 (95% CI = 1.26-5.3), absolute
      risk reduction was 23% and number-needed-to-treat (NNT) to prevent one recurrence
      was 5. CONCLUSION: Thiopurine drugs (AZA/MP) are more effective than placebo for
      the prevention of relapse in UC, with an NNT of 5 and an absolute risk reduction
      of 23%.

PMID- 19392870
TI  - Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer
      risk.
AB  - BACKGROUND: In 1980, Garland hypothesized that lower levels of vitamin D
      resulting from much weaker UV-B radiation at higher latitudes may account for the
      striking geographical pattern of cancer mortality. Further research has been
      conducted over the past 20 years. AIM: To perform a systematic review and meta
      analysis of longitudinal studies on the association between serum 25
      hydroxyvitamin D (25(OH)D) and the risk of colorectal cancer (CRC). METHODS:
      Relevant studies published until September 2008 were identified by systematically
      searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross
      referencing. Due to the heterogeneity of studies in categorizing serum vitamin D
      levels, all results were recalculated for an increase of serum 25(OH)D by 20
      ng/mL. Summary odds ratios (ORs) were calculated using meta-analysis methods.
      RESULTS: Overall, eight original articles reporting on the association between
      serum 25(OH) D and CRC risk were included. In meta-analyses, summary ORs (95%
      confidence intervals) for the incidence of CRC, colon cancer and rectal cancer
      associated with an increase of 25(OH)D by 20 ng/mL were 0.57 (0.43-0.76), 0.78
      (0.54-1.13) and 0.41 (0.11-1.49). No indication for publication bias was found.
      CONCLUSIONS: Our results support suggestions that serum 25(OH)D is inversely
      related to CRC risk.

PMID- 19392871
TI  - Comparison of risk factors and clinical responses to proton pump inhibitors in
      patients with erosive oesophagitis and non-erosive reflux disease.
AB  - BACKGROUND: There has been no report on the response to proton pump inhibitor
      (PPI) therapy and on-demand or the relapse rate of non-erosive reflux disease
      (NERD) and erosive oesophagitis in Korea. AIM: To compare the risk factors,
      clinical symptoms and PPI responses between patients with erosive oesophagitis
      and NERD patients. METHODS: A survey was performed prospectively in the erosive
      oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms,
      risk factors and PPI responses were analysed. On-demand therapy and the relapse
      rate of GERD symptoms were investigated during a one-year follow-up. RESULTS: BMI
      > or = 25 (OR 3.0, 95% CI 1.1-8.3), alcohol use (OR 2.9, 95% CI 1.0-8.3), hiatal
      hernia (OR 5.0, 95% CI 1.2-20) and triglyceride > or =150 mg/dL (OR 4.0, 95% CI
      1.7-10) were more common in the erosive oesophagitis group than in the NERD group
      by multivariate analysis. The ratio of oesophageal to extra-oesophageal symptoms
      was higher in the erosive oesophagitis group compared with the NERD group (P <
      0.001). The PPI response rates at 8 weeks were different (P = 0.02); refractory
      rates were higher in the NERD group (16.7%) compared with the erosive
      oesophagitis group (6.0%). However, there was no significant difference between
      the two groups in on-demand therapy or the relapse rate. CONCLUSION: These
      results suggest that the underlying pathogenic mechanisms of erosive oesophagitis
      and NERD are distinct.

PMID- 19392872
TI  - The effect of strength training on the force of twitches evoked by corticospinal
      stimulation in humans.
AB  - AIM: Although there is considerable evidence that strength training causes
      adaptations in the central nervous system, many details remain unclear. Here we
      studied neuromuscular responses to strength training of the wrist by recording
      electromyographic and twitch responses to transcranial magnetic stimulation (TMS)
      and cervicomedullary stimulation of the corticospinal tract. METHODS: Seventeen
      participants performed 4 weeks (12 sessions) of strength training for the radial
      deviator (RD) muscles of the wrist (n = 8) or control training without external
      load (n = 9). TMS recruitment curves were constructed from stimuli at five to
      eight intensities ranging between 15% below resting motor threshold and maximal
      stimulator output, both at rest and during isometric wrist extension (EXT) and RD
      at 10% and 50% of maximal voluntary contraction (MVC). Responses to weak TMS and
      cervicomedullary stimulation (set to produce a response of 10% maximal M wave
      amplitude during 10% MVC EXT contraction) were also compared at contraction
      strengths ranging from 10% to 75% MVC. RESULTS: Isometric strength increased
      following strength training (10.7% for the RD MVC, 8.8% for the EXT MVC), but not
      control training. Strength training also significantly increased the amplitude of
      TMS- and cervicomedullary-evoked twitches during low-force contractions.
      Increases in the force-generating capacity of the wrist extensor muscles are
      unlikely to account for this finding because training did not affect the
      amplitude of twitches elicited by supra-maximal nerve stimulation. CONCLUSION:
      The data suggest that strength training induces adaptations that increase the net
      gain of corticospinal-motor neuronal projections to the trained muscles.

PMID- 19392873
TI  - Comparison of orbital prosthesis motility following enucleation or evisceration
      with sclerotomy with or without a motility coupling post in dogs.
AB  - OBJECTIVE: To evaluate motility of silicone orbital implants and corneoscleral
      prostheses, with and without use of a motility coupling post (MCP) in dogs.
      ANIMALS STUDIED: Eighteen mixed-breed dogs. PROCEDURES: The motility of an
      orbital silicone implant and corneoscleral prosthesis after enucleation (n = 6),
      evisceration (n = 6), or use of a MCP with evisceration (n = 6) in dogs were
      compared. One eye from each dog had surgery whereas the opposite eye was used as
      a control. Clinical evaluations were performed three times a week. Histopathology
      of the orbital tissues was performed 8 and 12 weeks after surgery. RESULTS:
      Implant motility in dogs with evisceration (vertical movement [VM] 8.04 +/- 2.13;
      horizontal movement [HM] 11 +/- 3.05) and evisceration with MCP (VM 9.61 +/-
      1.59); HM was significantly greater than the enucleation group (VM 0.51 +/- 0.5;
      HM 1.22 +/- 0.68) (P < 0.01). Prosthetic motility in dogs with evisceration with
      MCP was significantly greater than in dogs with evisceration; dogs with
      evisceration had significantly greater motility than dogs with enucleation (P <
      0.01). No postoperative complications were observed in any of the groups. No
      significant abnormalities were noted on histopathology. CONCLUSIONS: MCP
      placement in silicone orbital implants significantly enhanced the prosthetic
      motility in dogs. This study supports the use of MCP in silicone orbital implants
      to enhance corneoscleral prosthesis motility and cosmetics in dogs.

PMID- 19392874
TI  - Three-dimensional study on the effect of organophosphate pesticide
      'monocrotophos' on lens of fish and its recovery.
AB  - The present studies are based on the feedback provided by fish farmers practicing
      composite fish culture of carps. According to them, fish habitats are affected by
      pesticides draining from agricultural fields into their catchments, especially
      during the rainy season. The lenses of most of the cultured fish became opaque,
      resulting in poor overall growth. In the literature, there was mounting evidence
      of pesticide toxicity involving multiple tissues. However, the fish visual system
      has never been investigated particularly from the toxicological perspective. In
      this regard, we carried out comparative toxicological studies on the lens of
      Cyprinus carpio communis using three different sublethal concentrations (0.038,
      0.062 and 0.126 p.p.m.) of monocrotophos along with untreated controls for 30
      days. Lenses from all the groups were extracted and preserved in gluteraldehyde
      and osmium tetraoxide and dehydrated in increasing grades of acetone. After
      dehydration, tissues were conducted with gold to observe under SEM. The fish
      exposed to monocrotophos developed cataract. Furthermore, when fish from the
      monocrotophos-treated tanks were transferred to normal environmental conditions
      for the next 60 days, progressive lens degeneration was noted. To conclude,
      monocrotophos induces irreversible cataractous changes in the lens of C. carpio
      communis. The fish visual system has many similarities to mammals and may serve
      as a good model for comparative toxicologic and ophthalmologic studies.

PMID- 19392875
TI  - Functional and structural assessment of retinal sheet allograft transplantation
      in feline hereditary retinal degeneration.
AB  - PURPOSE: To investigate whether sheets of fetal retinal allografts can integrate
      into the dystrophic Abyssinian cat retina with progressive rod cone degeneration.
      METHODS: Fetal retinal sheets (cat gestational day 42), incubated with BDNF
      microspheres, were transplanted to the subretinal space of four cats at an early
      disease stage. Cats were studied by fundus examinations, bilateral full-field
      flash ERGs, and indocyanine green and fluorescein angiograms up to 4 months
      following surgery. E42 donor and transplanted eyes were analyzed by histology and
      immunohistochemistry for retinal markers. RESULTS: Funduscopy and angiography
      showed good integration of the transplants in two of four cats, including
      extension of host blood vessels into the transplant and some scarring in the
      host. In these two, transplants were found in the subretinal space with laminated
      areas, with photoreceptor outer segments in normal contacts with the host retinal
      pigment epithelium. In some areas, transplants appeared to be well-integrated
      within the host neural retina. Neither of these two cats showed functional
      improvement in ERGs. In the other two cats, only remnants of donor tissue were
      left. Transplants stained for all investigated cellular markers. No PKC
      immunoreactivity was detected in the fetal donor retina at E42, but developed in
      the 4-month-old grafts. CONCLUSIONS: Fetal sheet transplants can integrate well
      within a degenerating cat retina and develop good lamination of photoreceptors.
      Functional improvement was not demonstrated by ERG in cats with well-laminated
      grafts. Transplants need to be further evaluated in cat host retinas with a more
      advanced retinal degeneration using longer follow-up times.

PMID- 19392876
TI  - Basic fibroblast growth factor stimulates epithelial cell growth and epithelial
      wound healing in canine corneas.
AB  - OBJECTIVE: To evaluate the effect of basic fibroblast growth factor (bFGF) on the
      proliferation of canine corneal epithelial cells and epithelial wound healing.
      ANIMAL STUDIED: Canine corneal epithelial cells from the corneas of euthanized
      dogs and corneal epithelial wounds on one eye from each of 24 dogs. PROCEDURES:
      The proliferation of corneal epithelial cells in vitro was measured using the
      methylthiazolyl-tetrazolium (MTT) assay. A corneal wound on one eye of each dog
      was made with a corneal trephine (6 mm diameter). Four concentrations of bFGF, 0,
      100, 500, and 1000 ng/mL, were applied to the affected eyes of dogs, t.i.d.
      Fluorescein staining was used to assess closure of the corneal epithelial wound.
      RESULTS: The addition of bFGF resulted in a significant increase in epithelial
      proliferation at 24 h after culture, except 1 ng/mL bFGF. Cells with all bFGF
      treatments proliferated significantly at 48 and 96 h compared to those in the non
      bFGF group. bFGF at a concentration of 10 ng/mL promoted cell proliferation
      maximally. The wound healing rate in the bFGF-treated groups was greater than
      that in the control. All corneal wounds in bFGF-treated corneas closed by day 7,
      whereas two of six corneal wounds in the control showed poor healing. None of the
      eyes developed corneal clouding or neovascularization during the experiment.
      CONCLUSIONS: Basic fibroblast growth factor accelerated the proliferation of
      canine epithelial cells and effectively promoted corneal epithelial wound
      healing.

PMID- 19392877
TI  - Bilateral orbital and nasal aspergillosis in a cat.
AB  - A 12-year-old, 4 kg, castrated male Persian cat was referred with a 2-month
      history of sneezing and bilateral mucopurulent nasal discharge. Rhinoscopically
      acquired nasal biopsies at this time revealed bilateral lymphoplasmacytic
      rhinitis. A tapering dose of oral prednisone caused the complete remission of the
      clinical signs, but 2 months after discontinuation of the therapy, the rhinitis
      recurred and the OD became exophthalmic. Computed tomography showed a soft tissue
      mass in both sides of the nasal cavity, both frontal sinuses, the right orbit,
      and to a lesser extent the left orbit. A fine needle aspirate of the right orbit
      revealed pyogranulomatous inflammation and Aspergillus spp. hyphae. Repeat nasal
      biopsy demonstrated multi-focal necrosis and a mixed inflammatory cell process
      which now included macrophages and scattered septate fungal hyphae. A few days
      later the cat became bilaterally blind and a contrast enhancing lesion involving
      the optic chiasm was found on magnetic resonance imaging. Despite a poor
      prognosis, therapy consisted of exenteration of the right orbit and trephination
      of both frontal sinuses before the planned initiation of medical antifungal
      therapy. Unfortunately, the cat died of cardiac arrest intraoperatively.
      Aspergillus fumigatus was cultured from both orbits at necropsy. Orbital
      aspergillosis has been rarely reported in cats and its relationship with
      lymphoplasmacytic rhinitis is unclear. In this patient lymphoplasmacytic rhinitis
      or previous antibiotic/corticosteroid therapy may have allowed secondary fungal
      invasion of the nasal mucosa and subsequently both orbits and the brain.
      Alternatively, Aspergillus infection may have preceded the lymphoplasmacytic
      rhinitis.

PMID- 19392878
TI  - Brucella canis endophthalmitis in 3 dogs: clinical features, diagnosis, and
      treatment.
AB  - OBJECTIVE: To describe historical, clinical and diagnostic features of dogs with
      Brucella canis endophthalmitis and the response to medical therapy. ANIMALS
      STUDIED: Three dogs with naturally acquired B. canis endophthalmitis. PROCEDURE:
      Dogs were treated symptomatically with topical ophthalmic anti-inflammatories and
      a novel antimicrobial protocol that included doxycycline, enrofloxacin, rifampin
      and streptomycin. RESULTS: All dogs presented with chronic or recurrent uveitis
      in the absence of overt systemic disease. Clinical ophthalmologic abnormalities
      were unilateral in each dog and included mild-to-moderate anterior uveitis, iris
      hyperpigmentation, marked vitreal infiltrates, and multifocal chorioretinitis.
      Dogs were diagnosed with canine brucellosis serologically and by blood culture (n
      = 2 dogs) or polymerase chain reaction of aqueous humor and blood (n = 1 dog).
      Active ocular inflammation resolved in all dogs during treatment, with
      preservation of vision in 2 dogs. Following treatment, B. canis could not be
      cultured from blood samples and serological values declined with seronegativity
      achieved in all dogs after a median of 96 weeks (range: 36-112 weeks) of therapy.
      CONCLUSIONS: Brucella canis infection should be included in the differential
      diagnosis for dogs with intraocular inflammation, regardless of previous history
      or neuter status. This is the first report of apparently successful medical
      therapy of canine brucellosis with ocular involvement.

PMID- 19392881
TI  - Caution in expanding role of transplant professionals in assessing living organ
      donors.

PMID- 19392879
TI  - The use of canine models of inherited retinal degeneration to test novel
      therapeutic approaches.
AB  - Inherited retinal degenerations (RDs) are a common cause of blindness in dogs and
      in humans. Over the past two decades numerous genes causally associated with
      these diseases have been identified and several canine models have been used to
      improve our understanding of the molecular mechanisms of RDs, as well as to test
      the proof of principle and safety of novel therapies. This review briefly
      summarizes the drug delivery approaches and therapeutic strategies that have been
      and are currently tested in dogs, with a particular emphasis on corrective gene
      therapy, and retinal neuroprotection.

PMID- 19392880
TI  - Aging adversely impacts biological properties of human bone marrow-derived
      mesenchymal stem cells: implications for tissue engineering heart valve
      construction.
AB  - Our aim was to study the aging effects on the in vitro biological properties of
      bone marrow-derived mesenchymal stem cells (BMSCs) for construction of tissue
      engineered heart valves. BMSCs were taken from teenagers with congenital heart
      diseases, and middle-aged and elderly patients with valvular diseases.
      Proliferative abilities were compared among the three groups by using colony
      forming unit counting and growth curves (5-bromo-2'-deoxyuridine assay). Cell
      differentiation, vascular endothelial growth factor (VEGF) release under hypoxic
      condition, and migratory abilities were compared as well. Colony-forming units in
      the teenage group were significantly greater than those in the other two groups
      (P < 0.05), and significantly higher counts were observed in the middle age group
      than in the aged group (P < 0.05). Growth curves presented similar trends in
      which cells' proliferative abilities in the aged group decreased significantly (P
      < 0.05), while no differences were noted between the two nonaged groups. The
      differentiation potential to endothelial cells, osteoblasts and adipocytes, VEGF
      releases, and migratory abilities differed significantly between the aged group
      and nonaged groups (P < 0.05). However, no differences were noted between the two
      nonaged groups. BMSCs from older patients with heart valve diseases could be
      harvested and expanded successfully, and the phenotype and morphology were
      uniform as nonaged groups. However, the proliferative and differentiation
      properties of aged cells, as well as cytokine release and migratory abilities,
      are significantly impaired.

PMID- 19392882
TI  - Genotyping of Mycoplasma pneumoniae isolates using real-time PCR and high
      resolution melt analysis.
AB  - Mycoplasma pneumoniae is an important respiratory pathogen, accounting for up to
      25% of community-acquired pneumonia, and is a common cause of hospitalized
      pneumonia in otherwise healthy adults and children. Mycoplasma pneumoniae
      isolates can be classified into two main genomic groups (type 1 and type 2) based
      on sequence variation within the gene encoding the major adhesion molecule P1.
      Although numerous publications have described real-time PCR assays for the
      detection of M. pneumoniae, none has been able to discriminate the two genomic
      types. Here, a real-time PCR assay that can distinguish each type of M.
      pneumoniae utilizing high-resolution melt-curve analysis is reported. Using this
      method, 102 isolates obtained from patients from 1965 to the present, including
      those from recent outbreaks, were typed along with reference strains M129 (type
      1) and FH (type 2). The results show that 55 isolates (54%) can be classified as
      type 1 and 47 isolates (46%) as type 2, and 100% correlation was demonstrated
      when compared with a standard PCR-restriction fragment length polymorphism typing
      procedure. Typing of isolates obtained from recent outbreaks in the USA has
      revealed the presence of both types. This assay provides a rapid, reliable and
      convenient method for typing M. pneumoniae isolates and may be useful for
      surveillance purposes and epidemiological investigations, and may provide insight
      into the biology of M. pneumoniae distribution within populations.

PMID- 19392883
TI  - Changes in pneumococcal serotypes and antibiotypes carried by vaccinated and
      unvaccinated day-care centre attendees in Portugal, a country with widespread use
      of the seven-valent pneumococcal conjugate vaccine.
AB  - The seven-valent pneumococcal conjugate vaccine (PCV7) has been available in
      Portugal since June 2001, but is not included in the National Vaccination Plan.
      Its impact on colonization is unknown. A point-prevalence study to evaluate PCV7
      usage was carried out in 2006 among day-care centre attendees from the Lisbon
      area. Pneumococcal carriage rates, serotypes, and antibiotypes were determined
      and compared with results from a similar study conducted in 2001 before vaccine
      approval. In 2001 and 2006, 717 and 571 children, respectively, were enrolled. In
      2006, 45.9% of the participants were appropriately vaccinated and 11.5% were
      incompletely vaccinated. Carriage of pneumococci remained stable (64.9% in 2001;
      68.7% in 2006). Vaccine types (VT) decreased from 53.1% of all pneumococci to
      11.2% (p <0.001). Serotype replacement was observed among vaccinated and
      unvaccinated children. Non-vaccine types (NVT) 1, 6C, 7F, 15A, 16F, 21, 23A, 29,
      and non-typeable (NT) strains increased significantly; serotype 19A increased,
      but not significantly. Rates of resistance to penicillin, erythromycin,
      clindamycin and tetracycline remained stable (p >0.05) due to significant
      increases in intermediate resistance to penicillin (from 5.5% to 17.8%),
      erythromycin (from 9.2% to 21.8%), clindamycin (from 6.4% to 19.3%) and
      tetracycline (from 8.3% to 15.8%) among NVT. Whereas in 2001 resistance among NVT
      was mostly associated with serotype 19A and NT strains, in 2006 resistance was
      also found among serotypes 6C, 15A, 24F and 33F. In conclusion, dramatic shifts
      in serotypes of colonizing pneumococci were observed among vaccinated and
      unvaccinated children. Rates of antibiotic resistance remained unchanged due to a
      balance between reduction in VT and an increase in antimicrobial-resistant NVT.

PMID- 19392884
TI  - Increased levels of immunological markers in the respiratory tract but not in
      serum correlate with active pulmonary mycobacterial infection in mice.
AB  - Immunological tests for the diagnosis of tuberculosis (TB) have relied mostly on
      detection of immune markers in serum or release of cytokines by mononuclear cells
      in vitro. These tests, although useful, sometimes fail to discriminate between
      active infection and contact with mycobacteria or vaccination. TB is primarily a
      disease of the lung, and therefore identification of immunological markers in the
      respiratory tract will be more likely to reflect the infection status or disease
      activity. In this study, it is demonstrated that active infection of mice with
      Mycobacterium bovis bacille Calmette-Guerin (BCG), but not exposure to heat
      killed BCG, induced production of interleukin-12 (IL-12), interferon-gamma (IFN
      gamma) or soluble tumour necrosis factor receptors (sTNFRs) locally in the lungs,
      as detected in bronchoalveolar lavage (BAL) fluid. There was a strong correlation
      between bacterial growth in the lung and levels of sTNFRs, and to some extent IL
      12 and IFN-gamma, in BAL fluid. Furthermore, sTNFR levels increased significantly
      in BAL fluid after reactivation of controlled infection with dexamethasone, and
      this correlated with increased bacterial growth in the lungs. Finally, infection,
      but not exposure to non-replicating mycobacteria, induced specific IgG and IgA in
      BAL fluid. Elevated levels of all biomarkers measured were also detected in the
      serum, but correlation with infection was not as clear as in the case of BAL
      fluid. Taken together, the detection of sTNFRs and mycobacterium-specific
      antibodies, especially IgA, locally in the lungs could be used as immunological
      markers for the diagnosis of TB.

PMID- 19392885
TI  - High-resolution melting analysis of the spa locus reveals significant diversity
      within sequence type 93 methicillin-resistant Staphylococcus aureus from northern
      Australia.
AB  - High-resolution melting analysis is an inherently robust, easy and inexpensive
      approach to the examination of genomic regions containing single-nucleotide
      polymorphisms and hypervariable loci. Staphylococcus aureus sequence type (ST) 93
      is a singleton, Panton-Valentine leukocidin-positive clone unique to Australia. A
      high-resolution melting-based method for the identification of ST93 was
      developed, and a similar approach was used to reveal diversity within the spa
      locus of this lineage. Statistical and graphical methods that account for
      instrumental and operator-dependent variation in high-resolution melting curves
      were developed, to allow greater confidence and reproducibility in deciding
      whether another curve is truly different from the baseline curve of an amplicon
      with known sequence. The data support a very early acquisition, or multiple
      independent acquisitions, of SCCmec by ST93 methicillin-susceptible S. aureus
      (MSSA), and the coexistence of MSSA and methicillin-resistant S. aureus versions
      of the same lineage within northern Australia.

PMID- 19392886
TI  - Correlation between time to positivity of blood cultures with clinical
      presentation and outcomes in patients with Klebsiella pneumoniae bacteraemia:
      prospective cohort study.
AB  - Time to positivity (TTP) of blood cultures in patients with bacteraemia is
      considered to be a predictor of outcome for some bacterial species. Two hundred
      and thirty-one patients with Klebsiella pneumoniae monomicrobial bacteraemia at a
      hospital from 1 January to 31 December 2007 were prospectively enrolled. TTP <7 h
      (46 patients, 19.9%) was associated with a higher Pittsburg bacteraemia score
      (6.2 +/- 5.5 vs. 3.7 +/- 4.3, p 0.002), fewer non-fatal diseases by the McCabe
      classification (39.1% vs. 64.9%, p 0.002), a higher percentage of patients with
      liver cirrhosis, active malignancy, and chemotherapy within 3 months (28.3% vs.
      11.9%, p 0.007; 28.3% vs. 14.6%, p 0.031; 23.9% vs. 5.4%, p <0.001), more primary
      bacteraemia (45.7% vs. 22.2%, p 0.002), and a higher 30-day mortality rate (47.8%
      vs. 21.1%, p <0.001). Risk factors for 30-day mortality in the univariate
      analysis included higher Pittsburg bacteraemia score (5.8 +/- 5.3 vs. 3.7 +/-
      4.3, p 0.002), primary bacteraemia (41.0% vs. 21.8%, p 0.004), TTP <7 h (36.1%
      vs. 14.1%, p <0.001), and the presence of active malignancy (29.5% vs. 12.9%, p
      0.004). In the multivariate analysis, higher Pittsburg bacteraemia score (OR
      1.07; 95% CI 1.01-1.14), TTP <7 h (OR 2.46; 95% CI 1.20-5.05) and active
      malignancy (OR 2.21; 95% CI 1.03-4.73) were the significant factors associated
      with 30-day mortality. In the Kaplan-Meier survival curve, short TTP was
      significantly associated with mortality at all time-points after admission. TTP
      of blood cultures, interpreted with a cut-off point of <7 h, in patients with K.
      pneumoniae bacteraemia can provide useful prognostic information.

PMID- 19392887
TI  - Genetic variability of wild-type measles viruses, circulating in the Russian
      Federation during the implementation of the National Measles Elimination Program,
      2003-2007.
AB  - Genetic characterization of wild-type measles viruses (MVs) is an important
      component of laboratory surveillance of measles. In this study, a phylogenetic
      analysis was performed of the nucleoprotein gene sequences of 228 MVs isolated in
      the Russian Federation between 2003 and 2007. Five genotypes, D4, D5, D6, D8, and
      H1, were detected. From 1999 through the first 6 months of 2003, the most
      prevalent genotype in the European part of Russia was D4. All genotype D4-type
      viruses were closely related to each other (with overall sequence diversity of
      <or=0.9%), suggesting the presence of a single endemic MV strain. After 2003,
      viruses with closely related sequences within genotype D6 (<or=0.9% sequence
      diversity) were prevalent. During this time, there was a low level of indigenous
      transmission of genotype D6, and genotype D6 viruses were imported from
      neighbouring countries, which led to the identification of two lineages of
      genotype D6, i.e. D6a and D6b. Lineage D6a was closely related to viruses
      isolated in Turkey, Kazakhstan, and Uzbekistan, whereas lineage D6b was linked to
      a large outbreak in Ukraine in 2005-2006. Genotypes H1, D5 and D8 were associated
      with sporadic cases and clusters of transmission linked to importations. Enhanced
      vaccination interrupted the transmission of the previous endemic lineage D4 in
      2003 and of lineage D6a in 2005, although an accumulation of susceptible
      individuals in the population allowed for prolonged circulation of lineage D6b.
      These data on MV genotype distribution, in conjunction with the epidemiological
      data for measles, show considerable progress in measles control and suggest that
      regional elimination is possible.

PMID- 19392888
TI  - Biofilm formation by Propionibacterium acnes is a characteristic of invasive
      isolates.
AB  - Propionibacterium acnes is a common and probably underestimated cause of delayed
      joint prosthesis infection. Bacterial biofilm formation is central in the
      pathogenesis of infections related to foreign material, and P. acnes has been
      shown to form biofilm both in vitro and in vivo. Here, biofilm formation by 93 P.
      acnes isolates, either from invasive infections (n = 45) or from the skin of
      healthy people (n = 48), was analysed. The majority of isolates from deep
      infections produced biofilm in a microtitre model of biofilm formation, whereas
      the skin isolates were poor biofilm producers (p <0.001 for a difference). This
      indicates a role for biofilm formation in P. acnes virulence. The type
      distribution, as determined by sequencing of recA, was similar among isolates
      isolated from skin and from deep infections, demonstrating that P. acnes isolates
      with different genetic backgrounds have pathogenic potential. The biofilm formed
      on plastic and on bone cement was analysed by scanning electron microscopy (EM)
      and by transmission EM. The biofilm was seen as a 10-mum-thick layer covering the
      bacteria and was composed of filamentous as well as more amorphous structures.
      Interestingly, the presence of human plasma in solution or at the plastic surface
      inhibits biofilm formation, which could explain why P. acnes primarily infect
      plasma-poor environments of, for example, joint prostheses and cerebrospinal
      shunts. This work underlines the importance of biofilm formation in P. acnes
      pathogenesis, and shows that biofilm formation should be considered in the
      diagnosis and treatment of invasive P. acnes infections.

PMID- 19392889
TI  - Exotoxin-encoding gene content in community-acquired and hospital-acquired
      methicillin-resistant Staphylococcus aureus.
AB  - Reports of community-acquired methicillin-resistant Staphylococcus aureus (CA
      MRSA) causing hospital infections are increasing, and it is questionable whether
      the existing molecular definition of CA-MRSA is suitable for the characterization
      of all strains involved. The 821 methicillin-resistant S. aureus (MRSA) isolates
      recovered from patients in Health Region East, Norway during the period 1991-2006
      were characterized by multilocus sequence typing (MLST), staphylococcal cassette
      chromosome mec (SCCmec) typing, staphylococcal protein A (spa) gene typing, and
      their content of exotoxin-encoding genes. Cluster analysis based on exotoxin
      encoding gene content was performed to separate the MRSA isolates into valid
      clusters with respect to microbiological characteristics. The analysis gave a
      four-cluster structure, and the four toxin clusters differed in the genetic
      lineages they included and in the diversity of the genetic lineages. A few
      genetic lineages were present in several toxin clusters. These results support
      the theory that mobile genetic elements encoding virulence genes do not move
      randomly among genetic lineages, but are restricted by the clonal lineages'
      genetic background. Using the molecular criteria, MLST type, SCCmec type and the
      presence of the lucS/F-Panton-Valentine leukocidin (PVL) gene to define a CA-MRSA
      isolate, it was found that the CA-MRSA isolates mainly grouped together in two
      toxin clusters with a low prevalence of exotoxin-encoding genes. Statistical
      analyses supported the conclusion that toxin clusters with CA-MRSA genetic
      lineages were characterized by a low prevalence of exotoxin-encoding genes,
      whereas toxin clusters with hospital-acquired MRSA genetic lineages were
      characterized by a higher prevalence of exotoxin-encoding genes.

PMID- 19392890
TI  - Two chromosomally located qnrB variants, qnrB6 and the new qnrB16, in Citrobacter
      spp. isolates causing bacteraemia.
AB  - The objective of this study was to determine the prevalence of the plasmid-borne
      quinolone resistance genes qnrA, qnrB and qnrS in a collection of
      Enterobacteriaceae causing bacteraemia. The presence of the three genes was
      tested for using multiplex PCR in 306 clinical isolates. Plasmid analysis was
      performed using I-CeuI and S1 nuclease digestion and hybridization with specific
      probes for the qnr and 23S rRNA genes. Five strains were found to carry a qnr
      gene, one of which, qnrB16, a new variant of qnrB, was detected in a Citrobacter
      freundii isolate. The qnrB6 variant was found in two C. freundii isolates and in
      one Citrobacter werkmanii isolate. The qnrS2 gene was found in one Klebsiella
      pneumoniae isolate. The qnrA gene was not found in any of the isolates studied.
      The qnrS2 gene was located on a plasmid of c. 50 kb, whereas qnrB6 and qnrB16
      were inserted in the chromosome between pspF and the orf2, which had previously
      been found in a complex integron. In the Hospital Clinic of Barcelona, Spain, the
      prevalence of qnrB was higher than that of qnrA and qnrS. The importance of the
      description of the new qnrB16 is emphasized.

PMID- 19392891
TI  - Characterization of invasive isolates of Streptococcus pneumoniae among Taiwanese
      children.
AB  - Accurate molecular surveillance is important in monitoring the dynamics of
      Streptococcus pneumoniae. A prospective study was conducted to collect invasive
      isolates of S. pneumoniae from children for genetic analysis from January 2004 to
      December 2006 in Taiwan. PCRs were performed to detect the zmpC and zmpD genes,
      both encoding a metalloprotease virulence factor in pneumococci, among these
      invasive isolates. During the study period, 68 invasive isolates of S. pneumoniae
      were obtained for analysis. Serotype 14 was the most common type isolated from
      children with invasive disease and was significantly associated with pneumonia
      (OR 3.1; 95% CI] 1.1-8.8; p 0.035). Serotype 23F was significantly associated
      with bacteraemia (OR 7.5; 95% CI 1.8-31.3; p 0.006). The seven-valent conjugate
      vaccine covered 83.8% of invasive isolates, but non-vaccine serotypes were more
      frequently isolated from patients with underlying diseases than from patients
      without underlying diseases (p 0.007 by Fisher's exact test). Clonal complexes
      related to international clones Spain23F ST81, Spain6B ST95, England14 ST9,
      Taiwan19F ST236, Taiwan23F ST242 and Colombia23F ST338 accounted for 52.9% of
      invasive isolates. Dissemination of the penicillin-resistant clones ST876, ST46,
      ST76 and ST2889, which were first identified in Taiwan, was also found; 1.5% of
      these invasive isolates carried the zmpC gene, and 47.1% of these invasive
      isolates carried the zmpD gene. In conclusion, the spread of certain
      international clones and some domestic antibiotic-resistant clones resulted in
      invasive diseases among Taiwanese children.

PMID- 19392892
TI  - Clinical and haematological features in Anaplasma phagocytophilum seropositive
      dogs.

PMID- 19392893
TI  - Serologic survey for antibodies to Rickettsia among domestic and wild animal
      populations in Brazil.

PMID- 19392894
TI  - Anaplasma in ticks feeding on migrating birds and questing ticks in Lithuania and
      Norway.

PMID- 19392895
TI  - Q fever in northern Greece: epidemiological and clinical data from 58 acute and
      chronic cases.

PMID- 19392896
TI  - Brazilian spotted fever: two faces of a same disease? A comparative study of
      clinical aspects between an old and a new endemic area in Brazil.

PMID- 19392897
TI  - The dog as an epidemiological marker of Rickettsia conorii infection.

PMID- 19392898
TI  - Seroprevalence of Rickettsia typhi and Rickettsia felis in dogs from north
      eastern Spain.

PMID- 19392899
TI  - Evaluation of PCR-based assay in human serum samples for diagnosis of fatal cases
      of spotted fever group rickettsiosis.

PMID- 19392900
TI  - The association of vacA genotype and Helicobacter pylori-related disease in Latin
      American and African populations.
AB  - In the populations of Western countries, particular genotypes of the vacuolating
      cytotoxin gene, vacA (vacA s, signal region variants; vacA m, middle region
      variants) of Helicobacter pylori are believed to be risk factors for the
      development of peptic ulcers and gastric cancer. However, it was unclear whether
      these vacA gene variants are associated with the development of gastrointestinal
      diseases in developing nations. The relationship between vacA genotypes and H.
      pylori-related disease development in Latin American and African populations was
      investigated using meta-analysis of 2612 patients from Latin America (2285
      strains) and 520 patients from Africa (434 strains). The frequencies of vacA s
      and m genotypes differed between strains from Latin America (77.2% for s1 and
      68.1% for m1) and Africa (83.9% for s1 and 56.7% for m1). Latin American strains
      with s1 and m1 genotypes increased the risk of gastric cancer (OR 4.17, 95% CI
      2.49-6.98 for s1, and 3.59, 2.27-5.68 for m1) and peptic ulcers (e.g. 1.73, 1.37
      2.20 for s1). African strains with the s1 or m1 genotypes also increased the risk
      of peptic ulcers (8.69, 1.16-64.75 for s1) and gastric cancer (10.18, 2.36-43.84
      for m1). The cagA-positive genotype frequently coincided with s1 and m1 genotypes
      in both populations. Overall, the vacA s and m genotypes were related to gastric
      cancer and peptic ulcer development and might be useful markers of risk factors
      for gastrointestinal disease, especially in Latin America. Further studies will
      be required to evaluate the effects of vacA genotypes in African populations
      because of the small sample number currently available.

PMID- 19392901
TI  - The pathological effect of Helicobacter pylori infection on liver tissues in
      mice.
AB  - Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer,
      gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Some
      reports also suggest that it causes extragastric disease, including hepatitis. In
      this study, the pathological changes in the liver and gall bladder in H. pylori
      colonized C57BL/6 mice were investigated. Twenty mice were inoculated orally with
      H. pylori strain SS1, and ten controls were injected with phosphate-buffered
      saline. Gastric colonization with H. pylori was assessed at 2 months after
      inoculation. Mice were examined at 8 months by histopathology, culture for H.
      pylori, and PCR for specific H. pylori genes. All C57BL/6 mice infected with H.
      pylori for 8 months developed severe gastric mucosal inflammation. Three mice
      showed mild-to-moderate multifocal hepatitis. The gall bladder mucosa of one H.
      pylori-infected mouse showed thickening of the mucous membrane with mild
      submucosal lymphocytic infiltration. H. pylori was observed morphologically in
      four liver specimens and six gall bladders from infected mice by
      immunohistochemistry. Specific H. pylori genes were also detected in six liver
      samples from infected mice, six samples of bile, and two blood samples by nested
      PCR. Thus, H. pylori inoculated orally may reach the hepatobiliary system and
      cause inflammation as an independent aetiological factor. The pathway to the
      liver may be via the blood or the biliary system.

PMID- 19392902
TI  - Epidemiology and diagnostics of visceral leishmaniasis in Serbia.
AB  - A retrospective epidemiological and diagnostic study of visceral leishmaniasis
      (VL) was carried out during the period 2001-2007 and included patients suspected
      of VL who had been diagnosed at the Parasitological Laboratory at the Institute
      for Infectious and Tropical Diseases, Belgrade. Diagnosis of VL was confirmed by
      microscopic examination of Giemsa-stained bone marrow (BM) smears. BM smears from
      134 patients were examined; 22 cases of VL were diagnosed, the majority of which
      involved individuals who had been on holiday at the Montenegrian sea coast. The
      sensitivity of the initial BM smears was inadequate; this required the
      application of a serological test, adapted for routine use, for the diagnosis of
      VL.

PMID- 19392903
TI  - Commercial potting soils as an alternative infection source of Legionella
      pneumophila and other Legionella species in Switzerland.
AB  - Legionella spp. are pathogens that can cause Legionnaires' disease in humans
      through inhalation of contaminated aerosols. The principal reservoir for these
      microorganisms is water, but Legionella spp. have been isolated from composted
      vegetable and plant material, and from many potting mixes as well. In Australia,
      there have been several cases of Legionnaires' disease in which Legionella
      longbeachae has been isolated from potting soils. In Switzerland, the source of
      infection cannot always be identified as water or cooling towers: therefore, we
      have investigated 46 commercially available potting soils in Switzerland to
      determine the presence of Legionella spp. We were able to detect Legionella spp.
      in 45.7% (21/46) of the potting soil samples analysed by culture. Legionella
      pneumophila was present in 19.6% (9/46) of the samples and L. pneumophila
      serogroup 1 in 6.5% (3/46). Quantification by both culture and quantitative real
      time PCR revealed high concentrations of legionellae in potting soils, ranging
      between 10(3) CFU/g and 10(5) CFU/g and 10(4) genomic units (GU)/g and 10(6)
      GU/g, respectively. Thus, potting soils may represent an alternative reservoir
      for Legionella spp. in Switzerland.

PMID- 19392905
TI  - Multiplex real-time PCR and blood culture for identification of bloodstream
      pathogens in patients with suspected sepsis.
AB  - Severe sepsis is increasingly a cause of death. Rapid and correct initial
      antimicrobial treatment reduces mortality. The aetiological agent(s) cannot
      always be found in blood cultures (BCs). A novel multiplex PCR test (SeptiFast
      (alpha version)) that allows identification of 20 bacterial and fungal species
      directly from blood was used, comparatively with BC, in a multicentre trial of
      patients with suspected bacterial or fungal sepsis. Five hundred and fifty-eight
      paired samples from 359 patients were evaluated. The rate of positivity was 17%
      for BC and 26% for SeptiFast. Ninety-six microorganisms were isolated with BC,
      and 186 microorganisms were identified with SeptiFast; 231 microorganisms were
      found by combining the two tests. Of the 96 isolates identified with BC, 22
      isolates were considered to be contaminants. Of the remaining 74 non-contaminant
      BC isolates available for comparison with SeptiFast, 50 were identified as a
      species identical to the species identified with SeptiFast in the paired sample.
      Of the remaining 24 BC isolates for which the species, identified in the BC,
      could not be detected in the paired SeptiFast sample, 18 BC isolates were
      identified as a species included in the SeptiFast master list, and six BC
      isolates were identified as a species not included in the SeptiFast master list.
      With SeptiFast, 186 microorganisms were identified, 12 of which were considered
      to be contaminants. Of the 174 clinically relevant microorganisms identified with
      SeptiFast, 50 (29%) were detected by BC. More than half of the remaining
      microorganisms identified with SeptiFast (but not isolated after BC) were also
      found in routine cultures of other relevant samples taken from the patients.
      Future clinical studies should assess whether the use of SeptiFast is of
      significant advantage in the detection of bloodstream pathogens.

PMID- 19392904
TI  - Clonal dissemination of Enterococcus faecalis ST201 and Enterococcus faecium CC17
      ST64 containing Tn5382-vanB2 among 16 hospitals in Chile.
AB  - We report the clonal dissemination of ST201 Enterococcus faecalis carrying Tn5382
      vanB2 and of CC17-ST64 Enterococcus faecium carrying Tn5382-vanB2-ISEnfa110 among
      16 hospitals in four geographically distant regions in Chile. This is the first
      epidemiological characterization of vancomycin resistance in Chile, and also the
      first report of interhospital dissemination of enterococcal vanB2 in South
      America.

PMID- 19392906
TI  - Factors associated with delay to acyclovir administration in 184 patients with
      herpes simplex virus encephalitis.
AB  - The main predictor of outcomes in herpes simplex virus (HSV) encephalitis (HSE)
      is the delay between hospital admission and initiation of acyclovir. In this
      study, factors associated with late initiation of acyclovir were identified. The
      study included adults from northern France whose cerebrospinal fluid (CSF) was
      positive for HSV by PCR. Late initiation of acyclovir was defined as a delay of
      >1 day from hospital admission. In total, 184 patients were retrospectively
      enrolled from January 1991 to December 2002. The median age was 60 years (range:
      17-91), and 102 (55.4%) were male. Acyclovir was initiated >1 day after hospital
      admission in 68 patients (37.0%). According to multivariate analysis, independent
      risk factors for late initiation of acyclovir were severe underlying disease
      (Knaus score >or=C) (OR 4.1; 95% CI 1.5-11.7); alcohol abuse (OR 3.4; 95% CI 1.3
      8.9); and a delay of >1 day from admission to first brain imaging (OR 8.4; 95% CI
      3.9-18.0). In addition, univariate analysis suggested an association between a
      finding of <10 leukocytes/mm(3) in CSF at admission (OR 2.5; 95% CI 0.7-5.8).
      These characteristics were found in 26 (14.1%), 23 (12.5%), 66 (35.9%) and 27
      (14.7%) patients, respectively. One risk factor was identified in 109 (59.2%)
      patients, two in 29 (15.8%), and three in six (3.3%). Patients with HSE often
      present with severe underlying disease, chronic alcohol abuse, or atypical CSF
      findings, and such factors should not be allowed to delay diagnosis and
      administration of acyclovir.

PMID- 19392907
TI  - Prevalence and clinical relevance of corrected QT interval prolongation during
      methadone and buprenorphine treatment: a mortality assessment study.
AB  - AIMS: To determine the prevalence of corrected QT interval (QTc) prolongation
      among patients in opioid maintenance treatment (OMT) and to investigate mortality
      potentially attributable to QTc prolongation in the Norwegian OMT programme.
      PARTICIPANTS AND SETTING: Two hundred OMT patients in Oslo were recruited to the
      QTc assessment study between October 2006 and August 2007. The Norwegian register
      of all patients receiving OMT in Norway (January 1997-December 2003) and the
      national death certificate register were used to assess mortality. Mortality
      records were examined for the 90 deaths that had occurred among 2382 patients
      with 6450 total years in OMT. DESIGN AND MEASURES: The QTc interval was assessed
      by electrocardiography (ECG). All ECGs were examined by the same cardiologist,
      who was blind to patient history and medication. Mortality was calculated by
      cross-matching the OMT register and the national death certificate register:
      deaths that were possibly attributable to QTc prolongation were divided by the
      number of patient-years in OMT. FINDINGS: In the QTc assessment sample (n = 200),
      173 patients (86.5%) received methadone and 27 (13.5%) received buprenorphine. In
      the methadone group, 4.6% (n = 8) had a QTc above 500 milliseconds; 15% (n = 26)
      had a QTc interval above 470 milliseconds; and 28.9% (n = 50) had a QTc above 450
      milliseconds. All patients receiving buprenorphine (n = 27) had QTc results <450
      milliseconds. A positive dose-dependent association was identified between QTc
      length and dose of methadone, and all patients with a QTc above 500 milliseconds
      were taking methadone doses of 120 mg or more. OMT patient mortality, where QTc
      prolongation could not be excluded as the cause of death, was 0.06/100 patient
      years. Only one death among 3850 OMT initiations occurred within the first month
      of treatment. CONCLUSION: Of the methadone patients, 4.6% had QTc intervals above
      500 milliseconds. The maximum mortality attributable to QTc prolongation was low:
      0.06 per 100 patient-years.

PMID- 19392908
TI  - Extended treatment of older cigarette smokers.
AB  - AIMS: Tobacco dependence treatments achieve abstinence rates of 25-30% at 1 year.
      Low rates may reflect failure to conceptualize tobacco dependence as a chronic
      disorder. The aims of the present study were to determine the efficacy of
      extended cognitive behavioral and pharmacological interventions in smokers > or =
      50 years of age, and to determine if gender differences in efficacy existed.
      DESIGN: Open randomized clinical trial. SETTING: A free-standing, smoking
      treatment research clinic. PARTICIPANTS: A total of 402 smokers of > or = 10
      cigarettes per day, all 50 years of age or older. INTERVENTION: Participants
      completed a 12-week treatment that included group counseling, nicotine
      replacement therapy (NRT) and bupropion. Participants, independent of smoking
      status, were then assigned randomly to follow-up conditions: (i) standard
      treatment (ST; no further treatment); (ii) extended NRT (E-NRT; 40 weeks of
      nicotine gum availability); (iii) extended cognitive behavioral therapy (E-CBT;
      11 cognitive behavioral sessions over a 40-week period); or (iv) E-CBT plus E-NRT
      (E-combined; 11 cognitive behavioral sessions plus 40 weeks nicotine gum
      availability). MEASUREMENTS: Primary outcome variable was 7-day point prevalence
      cigarette abstinence verified biochemically at weeks 24, 52, 64 and 104.
      FINDINGS: The most clinically important findings were significant main effects
      for treatment condition, time and the treatment x time interaction. The E-CBT
      condition produced high cigarette abstinence rates that were maintained
      throughout the 2-year study period [(week 24 (58%), 52 (55%), 64 (55%) and 104
      (55%)], and was significantly more effective than E-NRT and ST across that
      period. No other treatment condition was significantly different to ST. No
      effects for gender were found. CONCLUSIONS: Extended cognitive behavioral
      treatments can produce high and stable cigarette abstinence rates for both men
      and women. NRT does not add to the efficacy of extended CBT, and may hamper its
      efficacy. Research is needed to determine if these results can be replicated in a
      sample with a greater range of ages, and improved upon with the addition of
      medications other than NRT.

PMID- 19392910
TI  - Association of tobacco dependence and quit attempt duration with Rasch-modeled
      withdrawal sensitivity using retrospective measures.
AB  - AIM: To examine whether Rasch modeling would yield a unidimensional withdrawal
      sensitivity measure correlating with factors associated with successful smoking
      cessation. DESIGN: The psychometric Rasch modeling approach was applied to
      estimate an underlying latent construct (withdrawal sensitivity) in retrospective
      responses from 1644 smokers who reported quitting for 3 or more months at least
      once. SETTING: Web-based, passcode-controlled self-administered computerized
      questionnaire. PARTICIPANTS: Randomly selected convenience sample of 1644 adult
      members of an e-mail invitation-only web panel drawn from consumer databases.
      MEASUREMENTS: Lifetime Tobacco Use Questionnaire, assessing tobacco use across
      the life-span, including demographics and respondent ratings of the severity of
      withdrawal symptoms experienced in respondents' first and most recent quit
      attempts lasting 3 or more months. FINDINGS: Rasch-modeled withdrawal sensitivity
      was generally unidimensional and was associated with longer periods of smoking
      cessation. One latent variable accounted for 74% of the variability in symptom
      scores. Rasch modeling with a single latent factor fitted withdrawal symptoms
      well, except for increased appetite, for which the fit was marginal. Demographic
      variables of education, gender and ethnicity were not related to changes in
      sensitivity. Correlates of greater withdrawal sensitivity in cessation attempts
      of at least 3 months included younger age at first quit attempt and indicators of
      tobacco dependence. CONCLUSION: The relationship between tobacco dependence
      symptoms and Rasch-model withdrawal sensitivity defines further the relationship
      between sensitivity and dependence. The findings demonstrate the utility of
      modeling to create an individual-specific sensitivity measure as a tool for
      exploring the relationships among sensitivity, dependence and cessation.

PMID- 19392909
TI  - Parents who quit smoking and their adult children's smoking cessation: a 20-year
      follow-up study.
AB  - AIMS: Extending our earlier findings from a longitudinal cohort study, this study
      examines parents' early and late smoking cessation as predictors of their young
      adult children's smoking cessation. DESIGN: Parents' early smoking cessation
      status was assessed when their children were aged 8 years; parents' late smoking
      cessation was assessed when their children were aged 17 years. Young adult
      children's smoking cessation, of at least 6 months duration, was assessed at age
      28 years. SETTING: Forty Washington State school districts. PARTICIPANTS AND
      MEASUREMENTS: Participants were 991 at least weekly smokers at age 17 whose
      parents were ever regular smokers and who also reported their smoking status at
      age 28. Questionnaire data were gathered on parents and their children (49%
      female and 91% Caucasian) in a longitudinal cohort (84% retention). FINDINGS:
      Among children who smoked daily at age 17, parents' quitting early (i.e. by the
      time their children were aged 8) was associated with a 1.7 times higher odds of
      these children quitting by age 28 compared to those whose parents did not quit
      [odds ratio (OR) 1.70; 95% confidence interval (CI) 1.23, 2.36]. Results were
      similar among children who smoked weekly at age 17 (OR 1.91; 95% CI 1.41, 2.58).
      There was a similar, but non-significant, pattern of results among those whose
      parents quit late. CONCLUSIONS: Supporting our earlier findings, results suggest
      that parents' early smoking cessation has a long-term influence on their adult
      children's smoking cessation. Parents who smoke should be encouraged to quit when
      their children are young.

PMID- 19392911
TI  - Ethyl glucuronide in hair. A sensitive and specific marker of chronic heavy
      drinking.
AB  - AIMS: This study aims to define a cut-off concentration for ethyl glucuronide in
      hair to determine if there was a history of heavy drinking. SETTINGS: Pavia,
      Italy. PARTICIPANTS: We analysed hair samples from 98 volunteers among
      teetotallers, social drinkers and heavy drinkers, whose ethanol daily intake
      (EDI) was estimated by means of a written questionnaire. MEASUREMENTS: Ethyl
      glucuronide hair concentration (HEtG) was measured by liquid chromatography
      tandem mass spectrometry (lower limit of quantification: 3 pg/mg) using a fully
      validated method. FINDINGS: The HEtG level providing the best compromise between
      sensitivity (0.92) and specificity (0.96) at detecting an EDI of 60 g or higher
      during the last 3 months was 27 pg/mg. None of the factors examined among those
      known to affect ethanol metabolism and/or the diagnostic power of other markers
      of ethanol use or hair analyses, including age, gender, body mass index, tobacco
      smoke, prevalent beverage, hair colour, cosmetic treatments and hygienic habits
      was found to influence marker performance significantly. However, the slight
      differences in HEtG performance observed for some factors (e.g. body mass index,
      smoke and hair treatments) require further studies on larger groups of
      individuals in order to assess their influence more precisely. CONCLUSIONS: Our
      results confirm further that HEtG is a sensitive and specific marker of chronic
      heavy drinking.

PMID- 19392912
TI  - Substance use and misuse in the aftermath of terrorism. A Bayesian meta-analysis.
AB  - AIM: To conduct a comprehensive analysis of the conflicting evidence on substance
      use and misuse following mass traumas such as terrorist incidents. METHODS: We
      reviewed and synthesized evidence from 31 population-based studies using Bayesian
      meta-analysis and meta-regression. RESULTS: The majority of the studied were
      conducted in the aftermath of the terrorist attacks of 11 September 2001.
      Controlling for exposure, type of incident and time since the event occurred,
      7.3% [95% credible interval (CrI) 1.1-32.5%] of a population can be expected to
      report increased alcohol consumption in the first 2 years following a terrorist
      event. There is, however, a 20% probability that the prevalence will be as high
      as 14%. The unadjusted prevalence of increased cigarette smoking following a
      terrorist event is 6.8% (95% Cr I 2.6-16.5%). Unadjusted reports of mixed drug
      use (including narcotics and prescription medications) was 16.3% (95% Cr I 1.3
      72.5%). CONCLUSIONS: These results underscore the potentially pervasive
      behavioral health effects of mass terrorism, and suggest that public health
      interventions may usefully consider substance use as an area of focus after such
      events.

PMID- 19392913
TI  - MIST--patching up the differences and the need for an independent overview.

PMID- 19392914
TI  - Further insights in the pain /depression dyad.

PMID- 19392915
TI  - Atrial fibrillation in myocardial infarction: predictors and prognosis.

PMID- 19392916
TI  - Single-pill combination therapy in hypertension: a rational or emotional
      construct?

PMID- 19392917
TI  - SEARCHing for JUPITER: starry-eyed optimism is not warranted.

PMID- 19392918
TI  - Lifestyle changes may impact outcomes of musculoskeletal complaints more than
      passive therapies.

PMID- 19392919
TI  - Observational studies: a review of study designs, challenges and strategies to
      reduce confounding.
AB  - There are several methods in which one can assess the relationship between an
      intervention and an outcome. Randomized controlled trials (RCTs) are considered
      as the gold standard for evaluating interventions. However, for many questions of
      clinical importance, RCTs would be impractical or unethical. Clinicians must rely
      on observational studies for the best available evidence when RCTs are
      unavailable. This article provides an overview of observational research designs
      to facilitate the understanding and appraising of their validity and
      applicability in clinical practice. Major methodological issues of observational
      studies including selection bias and confounding are also discussed. In addition,
      strategies to minimize these problems in the design and analytical phases of a
      study are highlighted. Knowledge of the strengths, weaknesses and recent
      methodological advances in observational studies can assist clinicians to make
      informed decisions about whether a particular observational study would provide
      useful information to enhance patient care.

PMID- 19392920
TI  - High levels of anxiety and depression have a negative effect on quality of life
      of women with chronic pelvic pain.
AB  - BACKGROUND: Chronic pelvic pain (CPP) is a common and complex disease whose cause
      is often clinically inexplicable, with consequent difficulty in diagnosis and
      treatment. Patients with CPP have high levels of anxiety and depression, with a
      consequent impairment of their quality of life. AIMS: The objective of this study
      was to determine the prevalence of anxiety and depression and their impact on the
      quality of life of women with CPP. MATERIALS AND METHODS: A cross-sectional
      controlled study was conducted on 52 patients with CPP and 54 women without pain.
      Depression and anxiety were evaluated by the Hospital Anxiety and Depression
      Scale, and quality of life was evaluated by the World Health Organization Quality
      of life Whoqol-bref questionnaire. Data were analysed statistically by the Mann
      Whitney U-test, the Fisher exact test, chi-square test and Spearman correlation
      test. RESULTS: The prevalence of anxiety was 73% and 37% in the CPP and control
      groups, respectively, and the prevalence of depression was 40% and 30%
      respectively. Significant differences between groups were observed in the
      physical, psychological and social domains. Patients with higher anxiety and
      depression scores present lower quality of life scores. DISCUSSION: The fact that
      DPC is a syndromic complex, many patients enter a chronic cycle of search for
      improvement of medical symptoms. The constant presence of pain may be responsible
      for affective changes in dynamics, family, social and sexual. Initially the
      person is facing the loss of a healthy body and active, to a state of dependence
      and limitations. In this study, patients with higher scores of anxiety and
      depression scores had lower quality of life and patients with lower scores of
      anxiety and depression had scores of quality of life. These results show that
      perhaps the depression and anxiety may be related to the negative impact on
      quality of life of these patients. CONCLUSION: In view of this association, we
      emphasise the importance of a specific approach to the treatment of anxiety and
      depression together with clinical treatment to improve the quality of life of
      these patients.

PMID- 19392921
TI  - Atrial fibrillation during acute myocardial infarction: association with all
      cause mortality and sudden death after 7-year of follow-up.
AB  - AIMS: Atrial fibrillation/flutter (AF/FL) is a common complication of acute
      myocardial infarction (AMI). Indeed, the determinants of AF/FL in AMI-patients
      and the association of AF/FL with mortality are not well-known. The purpose of
      the present study was to investigate the relationship between presence of AF/FL
      and mortality in patients with AMI and to report on predictors of AF/FL. METHODS:
      We studied 505 patients enrolled in three intensive care units with definite AMI
      and followed up for 7 years. No patient was lost to follow-up. Patients with
      AF/FL during the 1st week of hospitalisation were compared with those with steady
      sinus rhythm. End-points were all-cause mortality and modes of death. RESULTS: At
      multivariable logistic regression analysis, elderly, body mass index, congestive
      heart failure (CHF), history of hypertension and plasma cholesterol (in a
      negative fashion) were independently associated with the presence of AF/FL. At
      survival analysis, after full adjustment, AF/FL was not associated with in
      hospital mortality. After 7 years of follow-up, AF/FL was found to be associated
      with all-cause mortality [adjusted odds ratio (OR) = 1.6; 95% confidence interval
      (CI) = 1.2-2.3], together with age, diabetes mellitus, creatine kinase-MB
      isoenzyme (CK-MB) peak, CHF, estimated glomerular filtration rate and
      thrombolysis. At adjusted logistic polynomial regression analysis, AF/FL was
      found to be associated with an excess of mortality for reasons of sudden death
      (SD) (adjusted OR = 2.7; 95% CI = 1.2-6.4). No interaction was observed between
      AF/FL and medications on in-hospital mortality. For 7-year mortality, angiotensin
      converting enzyme (ACE)-inhibitors and digitalis showed an independent negative
      (protective) interaction chiefly on SD (adjusted OR = 0.06; 95% CI = 0.01-0.74,
      and RR = 0.10; 95% CI = 0.02-0.58, respectively). CONCLUSIONS: Patients with AMI
      and AF/FL portend a poor prognosis in the long-term chiefly because of an excess
      of SD. Treatment with ACE-inhibitors and digitalis may have long-term beneficial
      effects on SD.

PMID- 19392922
TI  - Self-reported diagnosis of heart disease: results from the SHIELD study.
AB  - OBJECTIVE: This study evaluated the self-reported method of diagnosis of heart
      disease (HD) to elucidate whether diagnosis is occurring at early, presymptomatic
      stages as recommended by the prevention guidelines. METHODS: Respondents to the
      2006 survey in the US population-based Study to Help Improve Early evaluation and
      management of risk factors Leading to Diabetes (SHIELD) reported whether a
      physician told them that they had HD, including heart attack, angina, heart
      failure, angioplasty or heart bypass surgery. Self-report of age at diagnosis,
      specialty of physician who made the diagnosis and whether the diagnosis was made
      after having symptoms, during routine screening or while being treated for
      another health problem were assessed. Year of diagnosis was categorised into 3
      year intervals from 1985 to 2006. Individuals with HD diagnosis with and without
      type 2 diabetes mellitus (T2DM) were compared using chi-square tests. RESULTS: Of
      1573 respondents reporting a diagnosis of HD, > 87% were white, > 49% were men
      and 38% had T2DM. Approximately 19% of respondents reported that their HD
      diagnosis was made during routine screening. A significantly greater percentage
      of HD respondents with T2DM reported the diagnosis being made based on symptoms
      (54%) and while being treated for another health problem (22%) compared with
      respondents without diabetes (48% symptoms and 15% other health problem, p >
      0.05). HD was diagnosed primarily by cardiologists (> 60%) and family doctors (>
      25%). CONCLUSION: There remains a missed opportunity to diagnose HD at earlier
      stages through routine screening or during treatment of other health conditions
      such as diabetes, as many individuals were not diagnosed until they were
      symptomatic.

PMID- 19392923
TI  - Metabolic syndrome and quality of life (QOL) using generalised and obesity
      specific QOL scales.
AB  - OBJECTIVES: We investigated the association between metabolic syndrome (MS) and
      health-related quality of life (HRQOL) assessed using generalised and obesity
      specific QOL instruments. METHODS: We recruited 456 outpatients [age: 19-81
      years, body mass index (BMI): 16.3-36.7 kg/m2] in the primary care division from
      12 general hospitals in Korea. HRQOL was measured using EuroQol comprising the
      health states descriptive system (EQ-5D) and visual analogue scale (EQ-VAS) as a
      general instrument. The Korean Obesity-related QOL scale (KOQOL) composed of six
      domains was used as a disease-specific QOL instrument. MS was defined on the
      basis of International Diabetes Federation (IDF) criteria with Korean-specific
      waist circumference cutoffs (men: 90 cm, women: 85 cm). RESULTS: Subjects with MS
      displayed significantly higher impairment of EQ-5D and KOQOL. Binary logistic
      regression analysis of MS patients with controls for age, gender, smoking,
      alcohol, exercise, education, income, marital status and medication history
      disclosed odds ratio (OR) values of 2.13 (1.33-3.41) for impaired total KOQOL,
      2.07 (1.31-3.27) for impaired physical health, 1.63 (1.03-2.60) for impaired work
      related health, 2.42 (1.45-4.04) for impaired routine life, 2.08 (1.27-3.40) for
      impaired sexual life and 2.56 (1.59-4.11) for diet distress. Among the EQ-5D
      dimensions, only pain/discomfort displayed a significantly increased OR of 1.60
      (1.01-2.56) in MS group. CONCLUSIONS: Subjects with MS displayed a significantly
      impaired HRQOL compared with those without MS. MS and HRQOL were more strongly
      associated in obesity-specific QOL than in generalised QOL.

PMID- 19392924
TI  - Impact of COPD severity on physical disability and daily living activities: EDIP
      EPOC I and EDIP-EPOC II studies.
AB  - AIMS: The severity of chronic obstructive pulmonary disease (COPD) is associated
      to patients' health-related quality of life (HRQL). Physical impairment
      increasingly affects daily activities creating economic, social and personal
      burden for patients and their families. This burden should be considered in the
      management of COPD patients; therefore, we intended to assess the impact of the
      disease severity on physical disability and daily activities. METHODS: Two
      epidemiological observational cross-sectional descriptive studies were carried
      out in 1596 patients with moderate COPD and 2012 patients with severe or very
      severe COPD in the routine clinical practice. Demographic and basic clinical
      epidemiological data were collected and patients completed questionnaires to
      assess their physical disability because of COPD [Medical Research Council
      (MRC)], COPD repercussion on daily activities [London Chest Activity of Daily
      Living (LCADL)], job, economy and family habits and their health status [EQ-5D
      visual analogue scale (VAS)]. RESULTS: In all, 37% of severe/very severe COPD
      patients and 10% of moderate (p < 0.0001) had MRC grades 4 and 5. Mean global
      LCADL was significantly higher in severe/very severe than in moderate patients
      [29.6 (CI 95%: 28.91-30.25) vs. 21.4 (CI 95%: 20.8-21.9); p < 0.0001]. COPD job
      impact and economic and family habits repercussions were significantly higher and
      health status significantly worse in severe/very severe cases than in patients
      with moderate COPD. CONCLUSIONS: COPD severity is highly associated with physical
      disability by MRC grading, with functionality on daily activities and with
      impairment of other social and clinical activities. Moderate COPD patients show
      already a significant degree of impairment in all these parameters.

PMID- 19392925
TI  - Valsartan vs. other angiotensin II receptor blockers in the treatment of
      hypertension: a meta-analytical approach.
AB  - OBJECTIVE: To compare the efficacy of valsartan in systolic (SBP) and diastolic
      blood pressure (DBP) reduction with other angiotensin II receptor blockers (ARBs)
      in essential hypertension. METHODS: Systematic literature search of databases
      between October 1997 and May 2008. Meta-analysis of short-term, double-blind,
      parallel group, randomised controlled trials (RCTs) for treatment of adult
      hypertension (DBP: 90-115 mmHg). Random-effects meta-regression adjusting for
      baseline blood pressure (BP) was used to analyse the data. Mean change in SBP and
      DBP was estimated for each individual drug and dose combination. RESULTS: In all,
      31 RCTs (n = 13,110 patients) were included in the analysis. Six studies include
      trial arms with candesartan, six irbesartan, 13 losartan, two olmesartan, five
      telmisartan and 12 valsartan. The weighted average reduction in mean SBP and DBP
      for valsartan 160 mg was -15.32 mmHg (95% CI: -17.09, -13.63) and -11.3 mmHg (95%
      CI: -12.15, -10.52) and for 320 mg was -15.85 mmHg (95% CI: -17.60, -14.12) and 
      11.97 mmHg (95% CI: -12.81, -11.16); these are statistically significantly
      greater reductions compared with losartan 100 mg, which was -12.01 mmHg (95% CI: 
      13.78, -10.25) and -9.37 mmHg (95% CI: -10.18, -8.54) for SBP and DBP
      respectively. There is evidence that valsartan 160 mg reduces SBP and DBP more
      than irbesartan 150 mg and reduced DBP more than candesartan 16 mg. No other
      statistically significant difference in efficacy is demonstrated. CONCLUSION:
      Valsartan administered at 160 or 320 mg is more effective at lowering BP than
      losartan 100 mg and shows comparable efficacy to other ARBs in patients with
      essential hypertension.

PMID- 19392926
TI  - New antiplatelet drugs: beyond aspirin and clopidogrel.
AB  - Antiplatelet therapy remains a cornerstone of modern management of
      atherothrombotic vascular disease. For many years, aspirin has been the mainstay
      of initial antiplatelet drug management in coronary heart disease, while the need
      for inhibition of other platelet activation pathways has led to the development
      of various other antiplatelet drugs, such as clopidogrel. An improved
      understanding of the underlying mechanisms involved in thrombogenesis has paved
      the way for further development of newer antiplatelet drug therapies. Various
      clinical studies have probed the effectiveness and risk profile of the newer
      antiplatelet drugs, such as prasugrel, in comparison with currently available
      drugs. Some newer agents such as prasugrel are close to being approved for
      clinical use, whereas other agents such as cangrelor and AZD6140 are in phase 3
      clinical trials. New drug classes, such as the thromboxane receptor antagonists
      (such as NCX-4016 and S18886), as well as platelet adhesion antagonists and
      thrombin receptor antagonists are similarly being evaluated for their efficacy
      and risk profile in phase I and II trials.

PMID- 19392927
TI  - Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of
      Alzheimer's disease: a review.
AB  - BACKGROUND: Cholinesterase inhibitors have all been available in oral
      formulations, but a rivastigmine transdermal patch has now been developed and is
      approved in many countries worldwide for the treatment of mild-to-moderate
      Alzheimer's disease (AD) (including the USA, Latin America, Europe and Asia).
      OBJECTIVES: To review the available pharmacokinetic data that supported the
      rationale behind the development of the rivastigmine transdermal patch and its
      clinical effects in dementia therapy. This article will also discuss how the
      patch may alter the treatment paradigm for patients with AD. RESULTS: The 9.5
      mg/24 h rivastigmine patch was shown to provide comparable exposure to the
      highest recommended doses of capsules (12 mg/day) with significantly lower
      maximum plasma concentration (Cmax 8.7 vs. 21.6 ng/ml) and slower absorption rate
      (tmax 8.1 vs. 1.4 h). In a clinical trial of 1195 AD patients, this translated
      into similar efficacy with three times fewer reports of nausea and vomiting (7.2%
      vs. 23.1%, and 6.2% vs. 17.0% respectively). Consequently, more patients in the
      9.5 mg/24 h patch group achieved their target therapeutic dose at the end of the
      study, compared with those in the 12 mg/day capsule group (95.9% vs. 64.4%).
      CONCLUSION: The rivastigmine patch provides continuous drug delivery over 24 h
      and similar efficacy to the highest recommended dose of oral rivastigmine with
      improved tolerability. This may allow patients to achieve optimal therapeutic
      doses and to benefit from a longer duration of treatment.

PMID- 19392928
TI  - Mometasone furoate: an effective anti-inflammatory with a well-defined safety and
      tolerability profile in the treatment of asthma.
AB  - Inhaled corticosteroids (ICS) are recommended as a controller medication in the
      most recent Global Initiative for Asthma and the National Heart, Lung and Blood
      Institute guidelines. Mometasone furoate (MF) is an effective, well-tolerated
      inhaled steroid and is indicated for the maintenance treatment of adult and
      adolescent patients (> or = 12 years) with persistent asthma. MF is approved for
      once or bid maintenance treatment of asthma (in patients previously receiving ICS
      or bronchodilators). Low systemic bioavailability and high relative binding
      affinity for the glucocorticoid receptor are properties of MF that allow for a
      favourable efficacy and tolerability profile. Inhaled MF has been shown to be an
      effective and well-tolerated controller medication for those patients with mild,
      moderate or severe persistent asthma. MF has recently been approved by the US
      regulatory authorities for use in children (4-11 years). Future developments
      include the combination of MF with the long-acting bronchodilators, formoterol
      and indacaterol, to provide additional options in the treatment of asthma.

PMID- 19392929
TI  - Cognitive testing and overactive bladder medications.

PMID- 19392930
TI  - Primary haemoperitoneum.

PMID- 19392931
TI  - Septum perforation due to the use of Ecbalium elaterium.

PMID- 19392932
TI  - Ectopic pregnancy following tubal sterilisation: a case report.

PMID- 19392934
TI  - Survival and its discontents: the case of British psychiatry.
AB  - Sub-divisions of labour in health settings are common and medical dominance and
      encroachment from competitors are well known. This article considers this general
      picture but in specific relation to mental health work in Britain and its
      particular features of recent contestation. British psychiatric orthodoxy has
      faced challenges to its legitimacy for over a century. However, since the 1980s,
      in the wake of de-institutionalisation and a new shared service commitment to
      'recovery', these challenges have taken new shape. They are explored by
      considering: the current ambit of mental health care; the sub-division of labour
      in specialist mental services; recent governmental expectations of the mental
      health workforce; and the contested legacy of theory and practice in mental
      health work. The conclusion is that the profession is not under immediate threat
      of collapse but that its fate may now rest on whether a biomedical or a
      biopsychosocial model of practice predominates in routine service delivery.

PMID- 19392935
TI  - Tacit knowledge of caring and embodied selfhood.
AB  - The tacit knowledge paradigm is gaining recognition as an important source of
      knowledge that informs clinical decision-making. It is, however, limited by an
      exclusive focus on knowledge acquired through clinical practice, and a consequent
      neglect of the primordial and socio-cultural significance of embodied selfhood,
      precisely what provides the foundational structure of tacit knowledge of caring
      and facilitates its manifestation. Drawing on findings from a qualitative study
      of 43 dementia care practitioners in Ontario, Canada that utilised research-based
      drama and focus group methodology, we argue that embodied selfhood is fundamental
      to tacit knowledge of caring. Results are analysed drawing upon the theoretical
      precepts of embodied selfhood that are rooted in Merleau-Ponty's (1962)
      reconceptualisation of perception and Bourdieu's (1977, 1990) notion of habitus.
      We conclude with a call for further exploration of the body as a site of the
      production of tacit knowledge.

PMID- 19392936
TI  - Market reforms in English primary medical care: medicine, habitus and the public
      sphere.
AB  - Drawing on interviews with English primary care doctors (GPs), this paper
      examines GP responses to reforms intended to introduce a market in primary health
      care. GPs' reactions are conceptualised in terms of a GP habitus, which takes for
      granted the superiority of 'public' providers (i.e. GP partnerships) in the
      provision of care. GPs are actively involved in the defence of the public sphere,
      which is neither a neo-liberal minimalist market state, nor a wholly altruistic
      state, responding to consumers' wants. The public sphere they defend is one in
      which boundaries are drawn about entitlements and GPs are actively engaged in
      defining and policing these boundaries. The GP habitus can be seen as shaping
      responses in ways which serve GP interests. In the context of struggles involving
      various social actors (e.g. private providers, third-party payers, patients) with
      different stakes in the field of general medical practice; this public service
      orientation may enable GPs to reap cultural capital. At the same time, the
      habitus constrains action in a way which limits resistance to reforms threatening
      GPs' interests, with GPs responding by coping, rather than downing tools or
      engaging in active confrontation.

PMID- 19392937
TI  - Medicine and management in a comparative perspective: the case of Denmark and
      England.
AB  - In health systems around the world the current trend has been for doctors to
      increase their participation in management. This has been taken to imply a common
      process of re-stratification with new divisions emerging between medical elites
      and the rank and file. However, our understanding of this change remains limited
      and it is open to question just how far one can generalize. In this paper we
      investigate this matter drawing on path dependency theory and ideas from the
      sociology of professions. Focusing on public management reforms in the hospital
      sectors of two European countries - Denmark and England - we note similarities in
      the timing and objectives of reforms, but also differences in the response of the
      medical profession. While in both countries new hybrid clinical management roles
      have been created, this process has advanced much further and has been more
      strongly supported by the medical profession in Denmark than in England. These
      findings suggest that processes of re-stratification are more path dependent than
      is frequently acknowledged. They also highlight the importance of national
      institutions that have shaped professional development and differences in the way
      reforms have been implemented in each country for explaining variation.

PMID- 19392938
TI  - The 'actualities' of knowledge work: an institutional ethnography of multi
      disciplinary primary health care teams.
AB  - This study is set against the backdrop of the evolving order of a health care
      system in a province implementing a set of concurrent reforms. The study
      investigates how 'knowledge work' of multi-disciplinary health care teams is
      actually done and how it is co-ordinated across sites. Knowledge work involves
      three processes: the creation of new knowledge during the transfer of knowledge,
      in the context of the application of knowledge to their collective clinical
      decision-making. Institutional ethnography is used to explore the social and
      institutional forces that shape the knowledge work of health care providers in
      and across multi-disciplinary teams by way of examining how the texts trans
      locally organise the formation and functioning of multi-disciplinary teams. The
      study confirms that in the course of their collective clinical decision-making,
      teams' dialogical exchange facilitates the articulation of tacit knowledge and
      opens up the communicative space for the creation of new knowledge. In addition
      to this confirmatory finding, the study contributes to the existing health
      related knowledge management by illustrating the importance of the social,
      communicative aspects of the knowledge processes, and in particular, the
      relationship between knowledge and the social organisation of power.

PMID- 19392939
TI  - Functions of health fatalism: fatalistic talk as face saving, uncertainty
      management, stress relief and sense making.
AB  - Much research on fatalism assumes that fatalistic statements represent a global
      outlook that conflicts with belief in the efficacy of health behaviours. Other
      scholars have suggested a more contextual approach, suggesting that fatalism
      fulfils personal and social functions. This study analyses 96 in-depth lay
      interviews in the US, most with low-income members of the general public, about
      four diseases: heart disease, lung cancer, diabetes and depression. Within these
      interviews, fatalistic statements always occurred alongside statements endorsing
      the utility of behaviours for protecting health. This usage pattern suggests that
      these statements may have useful functions, rather than being simply a
      repudiation of the utility of health choices. We examine four functions that are
      suggested by previous researchers or by the participants' comments: stress
      relief, uncertainty management, sense making and (less strongly) face saving. As
      these themes indicate, individuals often make fatalistic statements to express an
      understanding of locally or broadly limiting factors for health efficacy,
      including genes, spiritual agents, prior behaviours, personality, and other
      factors.

PMID- 19392940
TI  - Derivative benefits: exploring the body through complementary and alternative
      medicine.
AB  - Since the 1960s, in Western societies, there has been a striking growth of
      consumer interest in complementary or alternative medicine (CAM). In order to
      make this increased popularity intelligible this paper challenges stereotypical
      images of users' motives and the results of clinical studies of CAM by exploring
      bodily experiences of acupuncture, reflexology treatments, and mindfulness
      training. The study draws on 138 in-depth interviews with 46 clients, client
      diaries and observations of 92 clinical treatments in order to identify bodily
      experiences of health and care: experiences that are contested between forces of
      mastery, control and resistance. We discuss why clients continue to use CAM even
      when the treatments do not help or even after they have been relieved of their
      physiological or mental problems. The encounter between the client and CAM
      produces derivative benefits such as a fresh and sustained sense of bodily
      responsibility that induces new health practices.

PMID- 19392941
TI  - Victimization and PTSD in a Faroese youth total-population sample.
AB  - The prevalence of twenty traumatic events and negative life events in relation to
      posttraumatic stress disorder (PTSD) was studied in a Faroese total-population
      sample of 687 eighth-grade students with a mean age of 14.2 years. Ninety-four
      percent of the females and 89% of the males were directly exposed to or had
      witnessed at least one traumatic event or a negative life event. The odds ratios
      for PTSD after direct and indirect exposure to specific events are described. The
      lifetime prevalence of PTSD was 20%, whereas another 14% reached a subclinical
      level of PTSD. After exposure, females had PTSD more than twice as often as
      males. Being exposed to multiple traumatic events, living with a single parent,
      and having experienced a traumatic event or a negative life event within the last
      year were all associated with PTSD and its subscales.

PMID- 19392942
TI  - Chinese deaf adolescents' free recall of taxonomic, slot-filler, and thematic
      categories.
AB  - Four experiments were conducted to show that deaf adolescents tended to process
      information in different ways from hearing adolescents. Memorizing items
      sequentially shown on computer screens under the control of their articulators'
      movements, deaf adolescents tended to treat items that cohered as taxonomic,
      thematic, or slot-filler categories as isolated pieces of information. Having to
      perceive information by means of sign language, however, their achievements were
      not worse than those of hearing adolescents anymore, no matter whether the
      stimuli were presented as words or pictures. They could not only utilize
      categories relations to help memorize categories exemplars but were relatively
      better aware of slot-filler or thematic than taxonomic relations as well,
      suggesting that they had a relatively delayed development of taxonomic category
      representations in comparison with hearing adolescents.

PMID- 19392943
TI  - Experts on age estimation.
AB  - The aim of this investigation was to study the biases and accuracy in age
      estimation of persons selling alcohol. Two experiments are reported, both
      suggesting that the accuracy in age estimation of Swedish alcohol salespersons is
      higher than that of control persons. This expertise in age estimation is probably
      the result of the extensive training Swedish alcohol salespersons go through as a
      natural part of their profession. Nonetheless, their estimates were not free from
      bias. Salespersons overestimated the age of target persons below 20 years of age
      and thus too young to buy alcohol. The results also revealed that controls, in
      contrast to salespersons, assimilated their estimates towards their own age (i.e.
      an own-anchor effect). Furthermore, female participants were shown to estimate
      the age of old target persons (56-65 years) more accurately than male
      participants. These results are discussed in relation to previous findings on
      training in age estimation and present jurisdiction.

PMID- 19392944
TI  - Exercisers' perceptions of their fitness instructor's interacting style,
      perceived competence, and autonomy as a function of self-determined regulation to
      exercise, enjoyment, affect, and exercise frequency.
AB  - The primary purpose of the present investigation was to test the hypothesis,
      derived from Self-Determination Theory (SDT), that an individual's perceived
      competence and autonomy mediate the relationship between the exercisers'
      perception of their instructor's interaction style and the exercisers' motivation
      to exercise. A secondary purpose was to identify the affective and behavioral
      outcomes derived from self-determined regulation. It was hypothesized that SDT
      would significantly explain and predict exercise behavior. Participants consisted
      of 238 college students, 103 males and 135 females (M age = 20.4 years, SD =
      2.16), who volunteered to participate in the study. They were asked to complete a
      battery of questionnaires measuring instructor's interacting style, self
      regulation to exercise, perceived autonomy and competence, enjoyment, positive
      and negative affect, and exercise frequency. Using structural equation modeling
      with observed variables, the results showed that perceived competence and
      autonomy mediated the relationship between perceived instructor's interacting
      style and self-determined regulation. It was also found that self-determined
      regulation was significantly related to exercise enjoyment, positive affect, and
      exercise frequency. It was concluded that understanding the motivational factors
      and emotional and behavioral consequences of physical activity will partially
      explain an individual's motives to engage regularly in exercise.

PMID- 19392945
TI  - Empathizing, systemizing and finger length ratio in a Swedish sample.
AB  - The Empathy- and Systemizing Quotients (EQ and SQ, respectively; Baron-Cohen,
      2003) were determined in a Swedish sample consisting mainly of university
      undergraduates. Females had significantly higher EQ than males, who in turn
      scored higher on the SQ inventory. Gender explained 12-14% of the variation.
      Males were strikingly overrepresented in the group defined by a high SQ/low EQ
      profile or by a large SQ - EQ difference; females dominated among people with a
      low SQ/high EQ profile or by a large EQ - SQ difference. Students majoring in the
      natural sciences had higher SQs than psychology majors, but in both groups the
      gender difference in SQ and EQ was strong. For each participant a weighted
      composite score was generated by multivariate processing of the EQ and SQ data
      (Partial Least Square Discriminant Analysis). These scores were associated in a
      sex-linked fashion to a biometric measure reflecting prenatal testosterone
      exposure, i.e. the ratio between index (2D)- and ring (4D) finger lengths. In
      males a high (female-typical) 2D:4D ratio predicted an enhanced tendency to
      empathize and a reduced tendency to systemize; in women, by contrast, the 2D:4D
      ratio was unrelated to these traits. The present research confirms earlier work
      of a gender difference in EQ and SQ. The difference appears robust as it appears
      as large in Sweden (a country with high cultural gender-equality) as in countries
      with considerably lower gender-equality.

PMID- 19392946
TI  - The influence of temporal distance on justice and care morality.
AB  - The primary goal of this study was to examine whether changes in the temporal
      distance of a moral dilemma affect how it is perceived and subsequently resolved.
      Based on Construal Level Theory (Trope & Liberman, 2003), it was predicted that
      the relative weight of abstract justice features should increase and the relative
      weight of concrete care features should decrease with temporal distance. The
      results showed that females became increasingly justice-oriented with greater
      temporal distance. However, this was not the case for males who were unaffected
      by temporal distance. This interaction was conceptually replicated in a follow-up
      experiment in which abstraction was manipulated directly by a mindset
      manipulation. The present results suggest that temporal distance is a contextual
      factor that can alter the extent to which moral judgments and reasoning are based
      on justice and care, although this effect seems to be moderated by gender.

PMID- 19392947
TI  - Indirect interception actions by blind and visually impaired perceivers:
      echolocation for interceptive actions.
AB  - This research examined the acoustic information used to support interceptive
      actions by the blind. Congenitally blind and severely visually impaired
      participants (all wearing an opaque, black eye-mask) were asked to listen to a
      target ball rolling down a track. In response, participants rolled their own ball
      along a perpendicular path to intercept the target. To better understand what
      information was used the echoic conditions and rolling dynamics of the target
      were varied across test sessions. In addition the rolling speed of the target and
      the distance of the participant from the target were varied across trials.
      Results demonstrated that participants tended to perform most accurately at
      moderate speeds and distances, overestimating the target's arrival at the fastest
      speed, and underestimating it at the slowest speed. However, changes to the
      target's dynamics, that is, the amount of deceleration it underwent on approach,
      did not strongly influence performance. Echoic conditions were found to affect
      performance, as participants were slightly more accurate in conditions with
      faster, higher-intensity echoes. Based on these results blind individuals in this
      research seemed to be using spatial and temporal cues to coordinate their
      interceptive actions.

PMID- 19392948
TI  - When tolerance leads to intolerance: accessibility effects on social judgment.
AB  - We investigated the effects of unobtrusively primed constructs that were
      evocative of tolerance (e.g., tolerant, nonprejudiced) on subsequent task
      performances and found, contrary to our expectation, contrast effects in the
      judgment of an ambiguous behavioral description (Study 1 and 2). Suspecting that
      these results might be the outcome of social-comparison processes, in Study 3, we
      attempted to corroborate our findings by providing the participants with either
      an explicit or implicit comparison standard. The results showed that the
      participants who were provided with the implicit comparison standard evaluated
      the target behavior as more intolerant as compared to those with the explicit or
      no comparison standard. The results are discussed in relation to the moderating
      role of automatic social-comparison processes in the incidence of assimilation
      and contrast effects and the reduction of prejudice.

PMID- 19392949
TI  - Is dengue a threat to the blood supply?
AB  - Dengue is the most common arthropod-borne infection worldwide, affecting at least
      50 million people every year and endemic in more than 100 countries. The dengue
      virus is a single-stranded RNA virus with four major serotypes. Infection with
      one serotype confers homotypic immunity but not heterologous immunity, and
      secondary infection with another serotype may lead to more severe disease. The
      major route of transmission occurs through the Aedes aegypti mosquito vector, but
      dengue has also been transmitted through blood transfusion and organ
      transplantation. Infection results in a spectrum of clinical illness ranging from
      asymptomatic infection, undifferentiated fever, dengue fever, dengue haemorrhagic
      fever (DHF) to dengue shock syndrome (DSS). Dengue is spreading rapidly to new
      areas and with increasing frequency of major outbreaks. A trend has also been
      observed towards increasing age among infected patients. This will impact blood
      supply availability as more blood donors are deferred because of dengue infection
      or exposure to infection. The risk of transmission through transfusion of blood
      from asymptomatic viraemic donors will also increase. Although screening tests
      for dengue and effective pathogen reduction processes are now available for the
      blood supply, the value of implementing these costly measures needs to be
      carefully considered. Demand for platelets and fresh frozen plasma will rise with
      increasing number of DHF/DSS. Evidence-based guidelines for the clinical use of
      these blood components in the management of patients with DHF/DSS have not been
      well established, and inappropriate use will contribute to the challenges faced
      by blood services.

PMID- 19392950
TI  - The EASTR study: a new approach to determine the reasons for transfusion in
      epidemiological studies.
AB  - Previous studies of blood use have used different methods to obtain and classify
      transfusion indications. Before undertaking a national study of transfusion
      recipients, a pilot study was performed over 2 months at two teaching and two
      district general hospitals to match information from hospital transfusion
      laboratories with clinical coding data from the hospital's Patients
      Administration System to determine the indication for transfusion in 2468
      recipients. Data analysis revealed major limitations in the conventional use of
      primary diagnostic International Statistical Classification of Disease and
      Related Health Problems 10th Revision (ICD-10) or procedure Office of Population,
      Censuses and Surveys - Classification of Surgical Operations and Procedures - 4th
      Revision (OPCS-4) codes alone in allocating transfusion indications. A novel
      algorithm was developed, using both types of code, to select the probable
      indication for transfusion for each patient. A primary OPCS-4 code was selected
      for recipients transfused in relation to surgery (43%) and either the primary
      (36%) or the secondary (12%) ICD-10 code was chosen for recipients transfused for
      medical reasons. The remaining patients were unclassified. Selected codes were
      then collated into Epidemiology and Survival of Transfusion Recipients (EASTR)
      casemix groups (E-CMGs). The most frequent E-CMGs were haematology (15% of
      recipients), musculoskeletal (14%), digestive system (12%) and cardiac (10%). The
      haematology E-CMG includes patients with malignant and non-malignant blood
      disorders and recipients transfused for anaemia where no cause was listed.
      Recipients undergoing hip and knee replacement and coronary artery bypass
      grafting are within the musculoskeletal and cardiac E-CMGs. The digestive E-CMG
      includes recipients transfused for gastrointestinal (GI) bleeds and those
      undergoing GI surgery. This methodology provides a more useful means of
      establishing the probable indication for transfusion and arranging recipients
      into clinically relevant groups.

PMID- 19392951
TI  - Hospital blood inventory practice: the factors affecting stock level and wastage.
AB  - To analyse the Issuable Stock Index (days worth of stock) and wastage in relation
      to data continuously collected by the Blood Stocks Management Scheme (BSMS) with
      aspects of blood inventory management practice determined by the 2006 hospital
      inventory practice survey (IPS). The BSMS collects blood inventory data from
      hospitals and blood services in England, Wales and Northern Ireland. Data sets
      were constructed from information obtained from the 2006 IPS, which included
      questions on the crossmatch reservation period, methods for calculating the blood
      order and stock share relationships between hospitals. Two of the Scheme's
      measures that can indicate a hospital's blood inventory management performance
      were used to present blood stock and wastage data in a comparable format. Data
      were analysed using the Student's t-test. The results showed significantly lower
      inventory and wastage in hospitals which used a 24-h reservation period compared
      with 48 h (P = 0.02 and P = 0.04, respectively), and for hospitals that used
      their computer for calculating the blood order compared with those that used a
      'visual review' (P = 0.02 and P < or = 0.001, respectively). A strong correlation
      co-efficient (0.61) was found for a relationship between a hospital's stock level
      and wastage. The study showed that differences in stock management practice
      between hospitals are associated with significant differences in stock levels and
      wastage of blood. The paper identifies examples of best practice.

PMID- 19392952
TI  - Effect of a risk-based multifactorial fall prevention program on the incidence of
      falls.
AB  - OBJECTIVES: To evaluate the effects of a multifactorial fall prevention program
      on falls and to identify the subgroups that benefit the most. DESIGN: Randomized
      controlled trial. SETTING: Community-dwelling subjects who had fallen at least
      once during the previous 12 months. PARTICIPANTS: Five hundred ninety-one
      subjects randomized into intervention (IG) (n=293) and control (CG) (n=298)
      groups. INTERVENTION: A multifactorial 12-month fall prevention program.
      MEASUREMENTS: Incidence of falls. RESULTS: The intervention did not reduce the
      incidence of falls overall (incidence rate ratio (IRR) for IG vs CG=0.92, 95%
      confidence interval (CI)=0.72-1.19). In subgroup analyses, significant
      interactions between subgroups and groups (IG and CG) were found for depressive
      symptoms (P=.006), number of falls during the previous 12 months (P=.003), and
      self-perceived risk of falling (P=.045). The incidence of falls decreased in
      subjects with a higher number of depressive symptoms (IRR=0.50, 95% CI=0.28
      0.88), whereas it increased in those with a lower number of depressive symptoms
      (IRR=1.20, 95% CI=0.92-1.57). The incidence of falls decreased also in those with
      at least three previous falls (IRR=0.59, 95% CI=0.38-0.91) compared to those with
      one or two previous falls (IRR=1.28, 95% CI=0.95-1.72). The intervention was also
      more effective in subjects with high self-perceived risk of falling (IRR=0.77,
      95% CI=0.55-1.06) than in those with low self-perceived risk (IRR=1.28, 95%
      CI=0.88-1.86). CONCLUSION: The program was not effective in reducing falls in the
      total sample of community-dwelling subjects with a history of falling, but the
      incidence of falls decreased in participants with a higher number of depressive
      symptoms and in those with at least three falls.

PMID- 19392953
TI  - Prevalence of methicillin-resistant Staphylococcus aureus colonization in
      residents and staff in nursing homes in Northern Ireland.
AB  - OBJECTIVES: To determine the prevalence of, and factors associated with,
      methicillin-resistant Staphylococcus aureus (MRSA) colonization in residents and
      staff in nursing homes in one geographically defined health administration area
      of Northern Ireland. DESIGN: Point prevalence study. SETTING: Nursing homes.
      PARTICIPANTS: Residents and staff in nursing homes. MEASUREMENTS: Nasal swabs
      were taken from all consenting residents and staff. If relevant, residents also
      provided urine samples, and swabs were taken from wounds and indwelling devices.
      RESULTS: A total of 1,111 residents (66% of all residents) and 553 staff (86% of
      available staff) in 45 nursing homes participated. The combined prevalence rate
      of MRSA in the resident population was 23.3% (95% confidence interval (CI)=18.8
      27.7%) and 7.5% in staff (95% CI=5.1-9.9%). Residents who lived in nursing homes
      that were part of a chain were more likely to be colonized with MRSA (odds ratio
      (OR)=1.91, 95% CI=1.21-3.02) than those living in independently owned facilities.
      Residents were also more likely to be colonized if they lived in homes in which
      more than 12.5% of all screened healthcare staff (care assistants and nurses)
      were colonized with MRSA (OR=2.46, 95% CI=1.41-4.29) or if they lived in homes in
      which more than 15% of care assistants were colonized with MRSA (OR=2.64, 95%
      CI=1.58-4.42). CONCLUSION: The findings suggest that there is substantial
      colonization of MRSA in nursing home residents and staff in this one
      administrative health area. Implementation of infection control strategies should
      be given high priority in nursing homes.

PMID- 19392955
TI  - Fear of moving outdoors and development of outdoor walking difficulty in older
      people.
AB  - OBJECTIVES: To study which individual characteristics and environmental factors
      correlate with fear of moving outdoors and whether fear of moving outdoors
      predicts development of mobility limitation. DESIGN: Observational prospective
      cohort study and cross-sectional analyses. SETTING: Community and research
      center. PARTICIPANTS: Seven hundred twenty-seven community-living people aged 75
      to 81 were interviewed at baseline, of whom 314 took part in a 3.5-year follow
      up. MEASUREMENTS: Fear of moving outdoors and its potential individual and
      environmental correlates were assessed at baseline. Perceived difficulties in
      walking 0.5 km and 2 km were assessed twice a year over a 3.5-year period.
      RESULTS: At baseline, 65% of the women and 29% of the men reported fear of moving
      outdoors. Poor socioeconomic status; musculoskeletal diseases; slow walking
      speed; and the presence of poor street conditions, hills in the nearby
      environment, and noisy traffic correlated with fear of moving outdoors. At the
      first 6-month follow-up, participants with fear of moving outdoors had more than
      four times the adjusted risk (odds ratio (OR)=4.6, 95% confidence interval
      (CI)=1.92-11.00) of developing difficulties in walking 0.5 km and a three times
      greater adjusted risk (OR=3.10, 95% CI=1.49-6.46) for developing difficulty in
      walking 2 km compared with those without fear. The difference in the prevalence
      of walking difficulties remained statistically significant over the 3.5-year
      follow-up (P=.02 and P=.009, respectively). CONCLUSION: Fear of moving outdoors
      is common in older adults and increases the risk of developing self-reported
      difficulties in walking 0.5 km and 2 km. Knowledge about individual and
      environmental factors underlying fear of moving outdoors and finding ways to
      alleviate fear of moving outdoors are important for community planning and
      prevention of disability.

PMID- 19392954
TI  - Positive affect and incidence of frailty in elderly women caregivers and
      noncaregivers: results of Caregiver-Study of Osteoporotic Fractures.
AB  - OBJECTIVES: To determine whether positive affect is associated with a lower
      incidence of frailty over 2 years in elderly community-dwelling women and to test
      the stress-buffering hypothesis by evaluating whether these associations differed
      in caregivers and noncaregivers. DESIGN: Prospective cohort study with three
      annual interviews conducted in four U.S. communities between 1999 and 2004.
      SETTING: Home-based interviews. PARTICIPANTS: Three hundred thirty-seven
      caregiver and 617 noncaregiver participants from the Caregiver-Study of
      Osteoporotic Fractures (Caregiver-SOF) who were not frail at the baseline
      Caregiver-SOF interview. MEASUREMENTS: High and low positive affect and
      depressive symptoms were derived from the baseline 20-item Center for
      Epidemiologic Studies Depression Scale. Frailty was the development of three or
      more indicators (weight loss, exhaustion, slow walking speed, or weak grip
      strength) at the first or second follow-up interview. RESULTS: Respondents' mean
      age was 81.2. Caregivers and noncaregivers had similar levels of positive affect
      (56.3% vs 58.3%) and frailty incidence (15.4% vs 15.9%) but differed in perceived
      stress (mean Perceived Stress Scale score 16.7 vs 14.8, P<.001). Frailty risk was
      lower in respondents with high positive affect than in those with low positive
      affect in the total sample (adjusted hazard ratio (HR)=0.49, 95% confidence
      interval (CI)=0.35-0.70), caregivers (adjusted HR=0.44, 95% CI=0.24-0.80) and
      noncaregivers (adjusted HR=0.50, 95% CI=0.32-0.77). CONCLUSION: These findings
      add to the evidence that positive affect protects against health decline in older
      adults, although it had no additional stress-buffering effect on health in
      elderly caregivers.

PMID- 19392956
TI  - Prevalence of constipation symptoms in fecally incontinent nursing home
      residents.
AB  - OBJECTIVES: To determine the prevalence of constipation symptoms and the effects
      of a brief toileting assistance trial on constipation in a sample of fecally
      incontinent nursing home (NH) residents. DESIGN: Observational study. SETTING:
      Five NHs. PARTICIPANTS: One hundred eleven fecally incontinent NH residents.
      MEASURES: Research staff measured bowel movement frequency every 2 hours for 10
      days. The following week, residents were offered toileting assistance every 2
      hours for 2 days to determine resident straining, time required for a bowel
      movement, and resident perceptions of feeling empty after a bowel movement.
      Constipation data were abstracted from the medical record. RESULTS: The frequency
      of bowel movements during usual NH care was low (mean=0.32 per person per day),
      and most episodes were incontinent. The frequency of bowel movements increased
      significantly, to 0.82 per person per day, and most episodes were continent
      during the 2 days that research staff provided toileting assistance. Eleven
      percent of residents showed evidence of straining, and 21% of the time after a
      continent bowel movement, residents reported not feeling empty. Five percent of
      participants had medical record or Minimum Data Set documentation indicative of
      constipation symptoms. CONCLUSION: Low rates of bowel movements during the day
      that are potentially indicative of constipation were immediately improved during
      a 2-day trial of toileting assistance in approximately 68% of the residents,
      although other symptoms of constipation remained in a subset of residents who
      increased toileting frequency.

PMID- 19392957
TI  - Clostridium difficile infection in the "oldest" old: clinical outcomes in
      patients aged 80 and older.
AB  - OBJECTIVES: Clostridium difficile infection (CDI) represents a cause of
      substantial morbidity, particularly for older adults. Although older age is a
      risk factor for CDI, few studies have specifically focused on clinical outcomes
      in older adults, particularly the "oldest" old. DESIGN: Retrospective review.
      SETTING: University of Michigan Health System. PARTICIPANTS: All patients aged 80
      and older with a positive cytotoxin assay for C. difficile and a clinical course
      consistent with CDI during 2006. MEASUREMENTS: Clinical data were recorded,
      including comorbid conditions and treatment regimens, as well as outcomes,
      including treatment failure, infection relapse, and 90-day mortality. RESULTS:
      Seventy patients aged 80 and older (mean 84.0+/-4.1) with CDI were identified.
      Metronidazole was given as initial therapy in 65 (92.8%); 18 of these 65 (27.7%)
      experienced treatment failure, requiring subsequent use of oral vancomycin.
      Serious adverse events included three episodes of toxic megacolon, two requiring
      colectomy. One death was directly attributable to CDI. All-cause mortality was
      8.6% at 30 days and 17.1% at 90 days. Higher white blood cell (WBC) counts were
      independently associated with treatment failure (P=.02) and coronary artery
      disease with 90-day mortality (P=.02). CONCLUSION: In older adults with CDI,
      treatment failure on metronidazole occurred frequently and was associated with
      higher WBC count. Larger prospective studies are needed to determine risk factors
      for treatment failure and relapse in order to develop better paradigms for CDI
      treatment in older adults. Initial therapy with vancomycin may be appropriate for
      elderly patients, especially those with elevated WBC counts.

PMID- 19392958
TI  - Self-reported sleep duration and hypertension in older Spanish adults.
AB  - OBJECTIVES: To examine the association between self-reported sleep duration,
      prevalent and incident hypertension, and control of high blood pressure in older
      adults. DESIGN: Logistic regression models were used to investigate the
      associations of interest in a prospective cohort study conducted from 2001 to
      2003. SETTING: Cohort representative of the noninstitutionalized Spanish
      population. PARTICIPANTS: Three thousand six hundred eighty-six persons aged 60
      and older. MEASUREMENTS: Sleep duration was reported in 2001 by asking the
      participants "How many hours do you usually sleep per day (day and night)" and
      classified into categories (4-5, 6, 7, 8, 9, and 10-15 h/d. The outcome variables
      were prevalent hypertension (systolic blood pressure > or =140 mmHg, diastolic
      pressure > or =90 mmHg, or antihypertensive treatment in 2001), control of blood
      pressure (systolic blood pressure <140 mmHg and diastolic pressure <90 mmHg in
      subjects receiving antihypertensive treatment in 2001), and incident hypertension
      (diagnosis of hypertension during 2001-2003 in individuals with normal pressure
      in 2001). RESULTS: Compared with sleeping 7 hours, sleeping more or fewer hours
      was not significantly associated with prevalent hypertension (odds ratios (ORs)
      ranged from 0.82 (95% confidence interval (CI)=0.64-1.05) to 1.10 (95% CI 0.83
      1.46)), control of blood pressure (ORs ranged from 0.70 (95% CI 0.46-1.08) to
      0.97 (95% CI 0.60-1.56)), or incident hypertension (OR ranged from 0.54 (95% CI
      0.29-1.01) to 0.83 (95% CI 0.43-1.60)). The results were similar in both sexes.
      CONCLUSION: Self-reported sleep duration is not associated with hypertension in
      older adults.

PMID- 19392959
TI  - The effect of major and minor depression on Medicare home healthcare services
      use.
AB  - OBJECTIVES: To examine the associations between major and minor depression and
      categories of Medicare home healthcare use. DESIGN: Observational prospective
      study (1997-1999). SETTING: Visiting nurse agency in suburban New York State.
      PARTCIPANTS: Five hundred thirty-nine new Medicare admissions aged 65 and older
      (mean age 78.4), 65.1% female, and 15.0% nonwhite. Approximately 13.5% were
      diagnosed with major depression and another 10.8% with minor depression.
      MEASUREMENTS: Consensus "best estimate"Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition (DSM-IV) diagnoses for major and minor
      depression assessed using Structured Clinical Interviews for DSM-IV (SCID) plus
      medical charts. RESULTS: Major and minor depression appear to have little
      association with probability and amount of use of the types of Medicare home
      health care (skilled nurse, home health aide, therapist (physical, occupational,
      and speech), and medical social services). Overall, patients with minor
      depression appear to have utilization similar to that of patients with major
      depression. CONCLUSION: It seems likely that any potential incremental depression
      effect on utilization is being offset by the transitional medical state of the
      patients that entered Medicare home healthcare directly from a hospital, nursing
      home, or rehabilitation facility, and the overall severity of disability and
      chronic illness present in long-term home healthcare patients. Further research
      is required to determine whether similar findings occur in other home healthcare
      agencies and whether these are present under the current Medicare Prospective
      Payment System reimbursement mechanism.

PMID- 19392960
TI  - Correlation between symptoms and function in older adults with comorbidity.
AB  - OBJECTIVES: To describe the relationship between symptom scores and mobility
      function measures, assess whether symptom scores and disease scores are similarly
      associated with mobility function, and identify clusters of symptoms that are
      most strongly associated with functional status in older adults. DESIGN:
      Secondary analysis of cross-sectional data from three cohorts. SETTING: Academic
      medical center. PARTICIPANTS: One hundred ninety-five community-dwelling subjects
      with poor flexibility or cardiorespiratory fitness (fitness cohort), 211 female
      retirement community residents with vertebral fractures (VF cohort), and 61
      subjects with Parkinson's disease (PD cohort). MEASUREMENTS: Twenty-item self
      reported symptom scale, 17-item self-reported disease scale, Medical Outcomes
      Study 36-item Short Form Survey (SF-36) Physical Functioning Scale, 5-item Nagi
      Disability scale, 10-m walk time, supine to stand time. RESULTS: Symptom scores
      correlated with mobility function measures (Spearman correlation coefficients
      ranged from 0.222 to 0.509) at least as strongly as, if not more strongly than,
      did disease scores. Symptom scores remained associated with functional outcomes
      after controlling for disease score and demographic variables. Adding symptom
      scores to models that contained disease scores significantly increased the
      association with functional outcomes. In the fitness cohort, muscle weakness was
      the most explanatory single symptom, associated with an average decrease of 17.8
      points on the Physical Functioning Scale. A model that included only muscle
      weakness, pain, and shortness of breath accounted for 21.2% of the variability in
      the Physical Functioning Score. CONCLUSION: Symptoms represent useful indicators
      of disability burden in older adults and are promising targets for interventions
      to improve function in medically complex patients.

PMID- 19392961
TI  - Personality traits of centenarians' offspring.
AB  - OBJECTIVES: To determine whether the offspring of centenarians have personality
      characteristics that are distinct from the general population. DESIGN: Case
      control. SETTING: Nationwide U.S. sample. PARTICIPANTS: Unrelated offspring of
      centenarians (n=246, mean age 75) were compared with published norms.
      MEASUREMENTS: Using the NEO-Five-Factor Inventory (NEO-FFI) questionnaire,
      measures of the personality traits neuroticism, extraversion, openness,
      agreeableness, and conscientiousness were obtained. T-scores and percentiles were
      calculated according to sex and used to interpret the results. RESULTS: Male and
      female offspring of centenarians scored in the low range of published norms for
      neuroticism and in the high range for extraversion. The women also scored
      comparatively high in agreeableness. Otherwise, both sexes scored within normal
      range for conscientiousness and openness, and the men scored within normal range
      for agreeableness. CONCLUSION: Specific personality traits may be important to
      the relative successful aging demonstrated by the offspring of centenarians.
      Similarities across four of the five domains between male and female offspring is
      noteworthy and may relate to their successful aging. Measures of personality are
      an important phenotype to include in studies that assess genetic and
      environmental influences of longevity and successful aging.

PMID- 19392963
TI  - Detection of mild hyposalivation in elderly people based on the chewing time of
      specifically designed disc tests: diagnostic accuracy.
AB  - OBJECTIVES: To compare sialometry with chewing time (including swallowing) of
      specifically designed disc tests. DESIGN: Index test versus reference standard
      (sialometry; 60 patients); reliability study (10 patients). SETTING: Outpatient
      dental clinic and geriatric ward, Nice University Hospital, France. PARTICIPANTS:
      Thirty adults and 30 older patients (mean ages 47 and 84). INTERVENTION: Index
      test assessment in patients with and without hyposalivation. MEASUREMENTS: Data
      from medical files, interviews and oral examination were collected. Sialometry
      (stimulated salivary flow rate (SSFR) mL/min) and disc chewing times (seconds)
      were measured. RESULTS: Sialometry was too long and was inappropriate for five of
      the 30 older persons. Chewing times were negatively correlated to sialometry
      results (Spearman correlation coefficient (R)=0.77, P<.001). The threshold to
      diagnose hyposalivation (SSFR <1 mL/min) was 40 seconds (area under the receiver
      operating characteristic curve (AUC)=0.921, 100% sensitivity, 72% specificity).
      Twenty-seven subjects with a SSFR less than 1.5 mL/min had a chewing time longer
      than 40 seconds, suggesting that mild hyposalivation and eating difficulties were
      related (AUC=0.941, 93% sensitivity, 88% specificity). Mean chewing time was
      greater with xerostomia (51.9 vs 30.7 seconds, P<.001) but not with dental pain
      (39.5 vs 39.9, P=.96). Masticatory percentage (e.g., pairs of antagonistic teeth)
      had no effect on chewing time (SSFR <1 mL/min, AUC=0.921; SSFR <1.5 mL/min,
      AUC=0.950). Reliability was better for the disc test than for sialometry
      (intraclass correlation 0.85 vs 0.70). CONCLUSION: This disc test was conceived
      to detect mild hyposalivation in geriatric patients with impaired dental health.
      Early detection of hyposalivation could help to suppress or avoid xerostomia
      inducing drugs and to prevent oral infections and dental caries.

PMID- 19392962
TI  - Treatment practices of mild cognitive impairment in California Alzheimer's
      Disease Centers.
AB  - OBJECTIVES: To examine "real world" treatments for patients with mild cognitive
      impairment (MCI). DESIGN: Cross-sectional. SETTING: California Department of
      Public Health Alzheimer's Disease (AD) Research Centers of California.
      PARTICIPANTS: Five hundred seventy-eight patients diagnosed with MCI.
      MEASUREMENTS: All patients underwent comprehensive neurological and
      neuropsychological evaluations. Logistic regression models were used to determine
      patient characteristics associated with use of anti-AD medications, statins,
      antioxidants, and folic acid. RESULTS: One hundred sixty-six patients (28.7%)
      were taking anti-AD medications; use was associated with greater functional
      impairment, higher education, MCI subtype, and older age (P<.05 for all). Two
      hundred fifty-two patients (43.6%) were taking statins; use was associated with
      diabetes mellitus, hypertension, myocardial infarct, male sex, and MCI subtype
      (P<.05 for all). One hundred fifteen patients (19.9%) were taking antioxidants;
      use was associated with higher education and diabetes mellitus and varied
      according to site (P<.05 for all). Thirty-seven patients (6.4%) were taking folic
      acid; use was associated with nonwhite race, male sex, and greater functional
      impairment (P<.05 for all). CONCLUSION: This study suggests that patients with
      MCI are frequently being treated with "off label" cholinesterase inhibitors and
      memantine, as well as other possible cognition-enhancing drugs. Further
      investigation of the effect of treatment patterns on the clinical course of MCI
      is needed.

PMID- 19392964
TI  - Reliability and validity of prehospital case finding for depression and cognitive
      impairment.
AB  - OBJECTIVES: To evaluate the test-retest reliability, the concurrent criterion
      validity, and the construct validity of prehospital, emergency medical service
      (EMS) case finding for depression and cognitive impairment in older adults.
      DESIGN: Cross-sectional study. SETTING: Prehospital EMS system and hospital
      emergency department. PARTICIPANTS: EMS providers and community-dwelling older
      adult (aged > or =60) patients. INTERVENTIONS: Case finding instruments for
      depression (Patient Health Questionnaire-2; PHQ-2) and cognitive impairment (Six
      Item Screener). MEASUREMENTS: The reliability and validity of these instruments.
      RESULTS: Moderate test-retest reliability was found for prehospital application
      of the PHQ-2 (kappa=0.50) and Six-Item Screener (kappa=0.52), fair concurrent
      criterion validity for depression (kappa=0.36), and slight to fair concurrent
      criterion validity for cognitive impairment (kappa=0.11-0.23). Construct validity
      was demonstrated using the Multitrait-Multimethod Matrix. CONCLUSION: Moderate
      test-retest reliability and construct validity were demonstrated for prehospital
      case finding by EMS providers for cognitive impairment and depression using these
      instruments. Slight to fair concurrent criterion validity was found, a result
      that methodological limitations could explain. These findings provide additional
      support for the concept of using EMS providers to detect older adults at risk for
      these conditions. Further work is needed to confirm the validity and
      effectiveness of prehospital screening before such programs are implemented.

PMID- 19392966
TI  - Depression and serum lipids and lipoprotein in Chinese nonagenarians and
      centenarians.

PMID- 19392967
TI  - Monitoring falls in cohort studies of community-dwelling older women.

PMID- 19392968
TI  - Cognitive impairment and medical illness in Chinese nonagenarians and
      centenarians.

PMID- 19392969
TI  - Prescribing and enteral tubes in the general hospital.

PMID- 19392970
TI  - Senator John McCain's health status and the arrogance of preventive medicine.

PMID- 19392971
TI  - Predicting injury from falls in older adults: comparison of voluntary step
      reaction times in injured and noninjured fallers--a prospective study.

PMID- 19392972
TI  - Mandatory cognitive screening in hospitalized elderly people: are we missing the
      diagnosis?

PMID- 19392973
TI  - Gelastic presyncope: an unusual manifestation in an elderly patient.

PMID- 19392974
TI  - When and how older people discuss preferences for long-term care options.

PMID- 19392975
TI  - Flecainide toxicity in an older adult.

PMID- 19392976
TI  - Atrioventricular nodal re-entrant tachycardia ablation in a centenarian.

PMID- 19392977
TI  - Bullous pemphigoid in the course of breast diseases: both breasts, neoplasmatic
      tumor; right breast, neoplasmatic tumor; and mastopathy--presentation of three
      cases in women aged 65 and older.

PMID- 19392979
TI  - Suppression of Mamu-AG by RNA interference.
AB  - PROBLEM: The role of placental major histocompatibility complex (MHC) class I
      molecules in pregnancy is not well understood. Mamu-AG, the rhesus monkey
      homology of human leukocyte antigen (HLA)-G expressed in the human placenta, was
      targeted for degradation by RNA interference (RNAi), a powerful tool to aid in
      determining gene function, to determine the effect that this knockdown has on NK
      cell function. METHOD OF STUDY: A series of potential target short hairpin RNA
      (shRNA) sequences to suppress Mamu-AG expression was screened, which identified
      an optimal sequence to use in transfection experiments. Knockdown in two
      different Mamu-AG-expressing cell lines was measured by flow cytometry.
      Cytotoxicity assays were performed to correlate Mamu-AG expression with NK cell
      cytotoxicity. RESULTS: Decreased expression of Mamu-AG by short interfering RNA
      (siRNA) (70-80%) in cell types tested was associated with increased lysis of Mamu
      AG target cells. CONCLUSION: Target sequences have been identified that knocked
      down Mamu-AG expression by RNAi and increased lysis by NK cells. This supports
      the concept that NK cell receptors recognize this placental non-classical MHC
      class I molecule.

PMID- 19392980
TI  - The combination of the gastrointestinal integrin (alpha4beta7) and selectin
      ligand enhances T-Cell migration to the reproductive tract during infection with
      Chlamydia trachomatis.
AB  - PROBLEM: Chlamydia trachomatis causes sexually transmitted infection and
      reproductive dysfunction worldwide. Identifying a population of endocervical T
      cells to target in vaccine development is likely to enhance efficacy of a vaccine
      and reduce reproductive tract dysfunction. METHOD OF STUDY: Endocervical samples
      were obtained from young women and flow cytometric analysis was used to identify
      lymphocytes that appeared in the genital tract in response to sexually
      transmitted bacterial infections caused by C. trachomatis. RESULTS: Increased
      numbers of alpha4beta7+CLA+ memory T-cells, a unique T-cell phenotype, were found
      in the endocervix of human female subjects infected with C. trachomatis.
      CONCLUSION: A unique population of memory T lymphocytes expressing both
      alpha4beta7 and CLA gain access to reproductive tract tissues during a sexually
      transmitted infection with C. trachomatis and should be considered in development
      of vaccines against sexually transmitted infections.

PMID- 19392981
TI  - Two different homing pathways involving integrin beta7 and E-selectin
      significantly influence trafficking of CD4 cells to the genital tract following
      Chlamydia muridarum infection.
AB  - PROBLEM: Chlamydia trachomatis causes STI and reproductive dysfunction worldwide
      which is not preventable with antibiotics. Identifying a population of
      endocervical T cells to target in vaccine development would enhance efficacy.
      METHOD OF STUDY: Trafficking of murine CD4+ lymphocytes to Chlamydia muridarum
      infected genital tract (GT) tissue in vivo was measured using adoptive transfer
      studies of fluorescent CD4+ T cells from integrin beta7-/- mice or mice which
      lack E-selectin on endothelial cells. RESULTS: Murine in vivo migration studies
      showed that lack of alpha4beta7 or E-selectin significantly reduced trafficking
      of CD4 T cells to the GT of mice infected with C. muridarum. CONCLUSION: CD4+ T
      cells use at least two different adhesive mechanisms involving an integrin of the
      mucosal homing pathway and selectin pathway to accumulate in the GT during C.
      muridarum infection.

PMID- 19392982
TI  - Response to 'Different preparations of tacrolimus and medication errors'.

PMID- 19392983
TI  - Reassessing the impact of donor HLA-C genotype on long-term liver transplant
      survival.
AB  - HLA-C is the major inhibitory ligand for killer immunoglobulin-like receptors
      (KIRs) that are expressed on natural killer (NK) cells. Based on their KIR
      specificity, HLA-C alleles can be divided into two groups, termed HLA-C1 and HLA
      C2. Donor HLA-C group has recently been identified by Hanvesakul et al. (Am J
      Transplant 2008) as a critical determinant of clinical outcome following liver
      transplantation: Possession of at least one HLA-C group 2 allele by the donor was
      associated with significantly improved long-term graft and patient survival,
      presumably due to an inhibition of host NK cell function. To verify this study,
      we performed genotyping of 913 deceased liver donors for the relevant KIR
      epitopes of HLA-C and correlated the presence or absence of donor HLA-C2 genotype
      with graft and patient survival. In our study, donor HLA-C2 genotype had no
      impact on 10-year graft or patient survival. We cannot confirm a major role of
      donor HLA-C2 genotype on long-term allograft survival after liver
      transplantation.

PMID- 19392984
TI  - American Society of Transplant Surgeons transplant center outcomes requirements-
      a threat to innovation.
AB  - The transplant center regulations recently published by the Centers for Medicare
      and Medicaid (CMS) mandate that observed program-specific survival outcomes to
      fall within expected risk-adjusted outcomes. Meeting these outcomes is essential
      to continued participation in the Medicare program. Both donor and recipient
      variables not considered in current risk adjustment models can result in inferior
      outcomes and therefore may cause an overestimation of transplant center expected
      performance, precluding participation in the federally funded Medicare program.
      We reviewed the most recent four reporting periods published by the Scientific
      Registry for Transplant Recipients on their public website. We identified kidney,
      liver and heart transplant programs that were flagged for having outcomes
      statistically lower than expected as well as those that failed to meet CMS
      criteria. We also analyzed whether center volumes correlated with outcomes in
      these centers. We highlight the need for mitigating factors that could justify
      inferior outcomes under specific circumstances. Failure to reach consensus on
      such a mechanism for appeal may result in risk-averse behavior by transplant
      centers with respect to innovation and therefore hamper the ability to advance
      the field of transplantation. We propose a methodology that may address this
      emerging dilemma.

PMID- 19392985
TI  - The kidney allocation score: methodological problems, moral concerns and
      unintended consequences.
AB  - The growing disparity between the demand for and supply of kidneys for
      transplantation has generated interest in alternative systems of allocating
      kidneys from deceased donors. This personal viewpoint focuses attention on the
      Kidney Allocation Score (KAS) proposal promulgated by the UNOS/OPTN Kidney
      Committee. I identify several methodological and moral flaws in the proposed
      system, concluding that any iteration of the KAS proposal should be met with more
      skepticism than sanguinity.

PMID- 19392986
TI  - Neutrophilic airway inflammation is a main feature of induced sputum in nonatopic
      asthmatic children.
AB  - BACKGROUND: Asthma phenotypes are well described among children. However, there
      are few studies comparing airway inflammation in different clinical presentations
      of pediatric asthma. We tested the hypothesis that nonatopic asthma is associated
      with a predominant noneosinophilic inflammation in the airways, as assessed by
      induced sputum. The objective of this study was to evaluate the cytological
      characteristics of induced sputum (IS) in atopic (AA), nonatopic asthmatics (NAA)
      and nonatopic nonasthmatic children (NANA). METHODS: Of 90 selected children, 77
      met eligibility criteria for performing IS and were classified as: AA, n = 28,
      NAA, n = 29 and NANA, n = 19. Subjects answered to a set of ISAAC-based questions
      and were skin-tested for common aeroallergens. A defined series of exclusion
      criteria was applied. RESULTS: Induced sputum was obtained from 54 (70.1%)
      subjects (21 AA, 20 NAA and 13 NANA). Demographic data and mean FEV(1) were
      similar in the three groups. The proportion of eosinophils [median, inter
      quartile range (IQR)] was significantly higher in the sputum of AA [(6.0.)12)]
      compared with NAAs [0 (2)] and NANAs [0 (1)], P < 0.001. The proportion of
      children with sputum eosinophilia (eos > 3%) was also significantly higher in AA
      (71.4%) when compared with NAA (28.6%); none of the NANA had sputum eosinophilia.
      Nonatopic asthmatic children had significantly higher proportions and absolute
      number of neutrophils than AA and controls. CONCLUSIONS: The results suggest that
      nonatopic children present IS with a cell pattern that is predominantly
      neutrophilic while eosinophilia is the hallmark of airway inflammation in the
      majority of atopic wheezing children not treated with inhaled steroids.

PMID- 19392987
TI  - Impaired TLR-2 expression and TLR-2-mediated cytokine secretion in macrophages
      from patients with atopic dermatitis.
AB  - BACKGROUND: In many patients with atopic dermatitis (AD), the disease is
      complicated by their enhanced susceptibility to bacterial skin infections,
      especially with Staphylococcus aureus. The pattern recognition receptor toll-like
      receptor (TLR)-2 recognizes components of S. aureus, for example, lipoteichoic
      acid (LTA) and peptidoglycan (PGN) and, therefore, might be crucial in the
      pathogenesis and flare-ups of AD. OBJECTIVE: To investigate TLR-2 expression and
      cytokine secretion in macrophages from patients with AD compared to healthy
      controls upon TLR-2 stimulation with PGN, LTA and Pam3Cys. METHODS: Macrophages
      were cultivated from highly purified peripheral blood monocytes of AD patients
      and nonatopic healthy controls and stimulated with PGN, LTA and Pam3Cys in a time
      and dose-dependent manner. Afterwards, TLR-2 expression and cytokine secretion
      were measured on protein and mRNA level. TLR-1 and TLR-6 expression were
      investigated on the mRNA level. Immunohistochemical stainings from punch biopsies
      were performed to investigate TLR-2 expression in skin macrophages. RESULTS: We
      could clearly show that macrophages from patients with AD expressed significantly
      less TLR-2, whereas the expression pattern of TLR-1 and TLR-6 were not altered.
      Macrophages had a reduced capacity to produce pro-inflammatory cytokines such as
      IL-6, IL-8 and IL-1beta after stimulation with TLR-2 ligands. CONCLUSION: Our
      findings clearly show an impaired TLR-2 expression and functional differences of
      TLR-2-mediated effects on macrophages of AD patients compared to healthy controls
      which might contribute to the enhanced susceptibility to skin infections with S.
      aureus in AD.

PMID- 19392988
TI  - Treatment of acquired cold urticaria with rupatadine.

PMID- 19392989
TI  - The HLA allele marker for differentiating ASA hypersensitivity phenotypes.

PMID- 19392990
TI  - Omega 3 and 6 oils for primary prevention of allergic disease: systematic review
      and meta-analysis.
AB  - BACKGROUND: There is conflicting evidence on the use of omega 3 and omega 6
      supplementation for the prevention of allergic diseases. We conducted a
      systematic review evaluating the effectiveness of omega 3 and 6 oils for the
      primary prevention of sensitization and development of allergic disorders.
      METHODS: We searched The Cochrane Central Register of Controlled Trials, MEDLINE,
      EMBASE, LILACS, PsycInfo, AMED, ISI Web of Science and Google Scholar for double
      blind randomized controlled trials. Two authors independently assessed articles
      for inclusion. Meta-analyses were undertaken using fixed effects modelling, or
      random effects modelling in the event of detecting significant heterogeneity.
      RESULTS: Of the 3129 articles identified, 10 reports (representing six unique
      studies) satisfied the inclusion criteria. Four studies compared omega 3
      supplements with placebo and two studies compared omega 6 supplements with
      placebo. There was no clear evidence of benefit in relation to reduced risk of
      allergic sensitization or a favourable immunological profile. Meta-analyses
      failed to identify any consistent or clear benefits associated with use of omega
      3 [atopic eczema: RR = 1.10 (95% CI 0.78-1.54); asthma: RR = 0.81 (95% CI 0.53
      1.25); allergic rhinitis: RR = 0.80 (95% CI 0.34-1.89) or food allergy RR = 0.51
      (95% CI 0.10-2.55)] or omega 6 oils [atopic eczema: RR = 0.80 (95% CI 0.56-1.16)]
      for the prevention of clinical disease. CONCLUSIONS: Contrary to the evidence
      from basic science and epidemiological studies, our systematic review and meta
      analysis suggests that supplementation with omega 3 and omega 6 oils is probably
      unlikely to play an important role as a strategy for the primary prevention of
      sensitization or allergic disease.

PMID- 19392991
TI  - Decreased FOXP3 protein expression in patients with asthma.
AB  - BACKGROUND: T-regulatory cells (T(reg)) are important in balancing immune
      responses and maintaining peripheral tolerance. Current evidence suggests that
      asthma is characterized by a relative deficiency in T(reg), allowing T helper 2
      cells to expand. In this study, we aimed to evaluate circulating T(reg), defined
      by the protein FOXP3, in both control subjects and patients with stable asthma.
      METHODS: Peripheral blood mononuclear cells (PBMC) of control (n = 14) and
      asthmatic patients (n = 29) were labeled for CD4, CD25, and intracellular FOXP3
      and analyzed using flow cytometry. In CD3/CD28 stimulated PBMC, the effects of
      dexamethasone on the transcription factors T-bet, GATA-3, FOXP3, and RORc2 and
      representative cytokines were studied. RESULTS: In control subjects and asthmatic
      patients, numbers of peripheral blood CD4(+)CD25(high) and
      CD4(+)CD25(high)FOXP3(+) T-cells were similar. However, FOXP3 protein expression
      within CD4(+)CD25(high) T-cells was significantly decreased in asthmatic
      patients. There was a tendency for increased FOXP3 expression within
      CD4(+)CD25(high) T-cells in glucocorticosteroid-treated patients when compared to
      steroid-naive asthmatic patients. In stimulated PBMC, dexamethasone treatment
      increased the anti-/proinflammatory transcription ratios of FOXP3/GATA-3, FOXP3/T
      bet, and FOXP3/RORc2. CONCLUSION: Asthmatic patients have decreased FOXP3 protein
      expression within their CD4(+)CD25(high) T(reg). Our findings also suggest that
      treatment with inhaled glucocorticosteroids in asthmatics might increase this
      FOXP3 protein expression within the CD4(+)CD25(high) T-cell population.

PMID- 19392992
TI  - Genetic variation in CRTh2 influences development of allergic phenotypes.
AB  - BACKGROUND: Allergic disorders are characterized by an increase in the Th2
      cytokines IL-4, IL-5 and IL-13, produced primarily by Th2 cells. These cells are
      marked by the expression of CRTh2 (chemoattractant receptor-homologous molecule
      expressed on Th2 cells), a receptor for prostaglandin D(2). As genetic variation
      plays a significant role in the predisposition for allergic disorders, we
      investigated the influence of single nucleotide polymorphisms (SNPs) in CRTh2.
      METHODS: In a large study population of German children (n = 4264) from the
      International Study of Asthma and Allergy in Children (ISAAC II), six
      polymorphisms in CRTh2 were genotyped. Statistical analyses were performed using
      single SNP and haplotype analyses. RESULTS: Uncorrected associations among 
      6373G>A, +1431G>C and +1538A>G were observed with a number of allergic phenotypes
      (P < 0.05). After correction, association between +1431C and specific IgE to food
      allergens remained significant (P = 0.04). Associations of haplotype (H)3
      (containing +1538G) with reduced risk for asthma and H2 (containing +1431C) with
      increased risk for specific IgE to food allergens also remained significant after
      correction for multiple testing (P = 0.004). CONCLUSIONS: Genetic variation
      within CRTh2 modifies the development of allergic sensitization and asthma in a
      population of German children.

PMID- 19392993
TI  - The effects of selected probiotic strains on the development of eczema (the PandA
      study).
AB  - BACKGROUND: Modification of the intestinal microbiota by administration of
      probiotic bacteria may be a potential approach to prevent allergic disease. We
      aimed to study primary prevention of allergic disease in high-risk children by
      pre- and postnatal supplementation of selected probiotic bacteria. METHODS: In a
      double-blind, randomized, placebo-controlled trial, a mixture of probiotic
      bacteria selected by in-vitro experiments (Bifidobacterium bifidum,
      Bifidobacterium lactis, and Lactococcus lactis; Ecologic Panda) was prenatally
      administered to mothers of high-risk children (i.e. positive family history of
      allergic disease) and to their offspring for the first 12 months of life.
      RESULTS: Parental-reported eczema during the first 3 months of life was
      significantly lower in the intervention group compared with placebo, 6/50 vs
      15/52 (P = 0.035). After 3 months, the incidence of eczema was similar in both
      groups. Cumulative incidence of parental-reported eczema at 1 and 2 years was
      23/50 (intervention) vs 31/48 (placebo) and 27 (intervention) vs 34 (placebo),
      respectively. The number needed to treat was 5.9 at age 3 and 12 months and 6.7
      at age 2 years. The intervention group was significantly more frequently
      colonized with higher numbers of Lc. lactis. Furthermore, at age 3 months, in
      vitro production of IL-5 (146 pg/ml vs 72 pg/ml; P = 0.04) was decreased in the
      probiotic-group compared with the placebo-group. CONCLUSIONS: This particular
      combination of probiotic bacteria shows a preventive effect on the incidence of
      eczema in high-risk children, which seems to be sustained during the first 2
      years of life. In addition to previous studies, the preventive effect appears to
      be established within the first 3 months of life.

PMID- 19392994
TI  - GA2LEN (Global Allergy and Asthma European Network) addresses the allergy and
      asthma 'epidemic'.
AB  - Allergic diseases represent a major health problem in Europe. They are increasing
      in prevalence, severity and costs. The Global Allergy and Asthma European Network
      (GA(2)LEN), a Sixth EU Framework Program for Research and Technological
      Development (FP6) Network of Excellence, was created in 2005 as a vehicle to
      ensure excellence in research bringing together research and clinical
      institutions to combat fragmentation in the European research area and to tackle
      allergy in its globality. The Global Allergy and Asthma European Network has
      benefited greatly from the voluntary efforts of researchers who are strongly
      committed to this model of pan-European collaboration. The network was organized
      in order to increase networking for scientific projects in allergy and asthma
      around Europe and to make GA(2)LEN the world leader in the field. Besides these
      activities, research has also been carried out and the first papers are being
      published. Achievements of the Global Allergy and Asthma European Network can be
      grouped as follows: (i) those for a durable infrastructure built up during the
      project phase, (ii) those which are project-related and based on these novel
      infrastructures, and (iii) the development and implementation of guidelines. The
      major achievements of GA(2)LEN are reported in this paper.

PMID- 19392995
TI  - Administration regimens for sublingual immunotherapy to pollen allergens: what do
      we know?
AB  - The modalities of administration of sublingual immunotherapy (SLIT), including
      dosing, build-up phase, duration of the treatment, and frequency of the
      maintenance dose are largely variable. In the case of pollen (SLIT), the
      complexity increases, since preseasonal, coseasonal and pre-coseasonal regimens
      can be used. The administration regimens are of relevance from a practical point
      of view, but can also have economic implications. We review herein the available
      literature (randomized double blind controlled studies) on pollen SLIT, in order
      to derive experimentally-supported suggestions about the regimens of
      administration that should be preferred.

PMID- 19392996
TI  - Occupational asthma and rhinitis induced by a cephalosporin intermediate product:
      description of a case.

PMID- 19392997
TI  - Eosinophilic pneumonia in an asthmatic patient treated with omalizumab therapy:
      forme-fruste of Churg-Strauss syndrome?

PMID- 19392998
TI  - Cross-reactivity and tolerability of imipenem in patients with delayed-type, cell
      mediated hypersensitivity to beta-lactams.
AB  - BACKGROUND: Administration of imipenem-cilastatin to patients with IgE-mediated
      hypersensitivity to beta-lactams has always been considered potentially harmful.
      Recent studies have demonstrated the tolerability of carbapenems (imipenem
      cilastatin and meropenem) in patients with IgE-mediated hypersensitivity to beta
      lactams; there are no studies on this topic regarding patients with cell-mediated
      allergy to beta-lactams. The aim of this study is to assess cross-reactivity and
      tolerability of imipenem in patients with cell-mediated allergy to beta-lactams.
      METHODS: From our database we selected 73 patients with cell-mediated allergy to
      beta-lactams, diagnosed by means of immediate-type skin tests, delayed reading
      intradermal tests, patch tests and detection of specific IgE. Patients with
      negative patch tests with imipenem-cilastatin underwent an intramuscular test
      dosing. RESULTS: Our patients had a total of 94 nonimmediate reactions to
      penicillins. All patients had positive patch tests and/or delayed reading
      intradermal tests for at least one of the penicillin reagent tested and negative
      immediate-type skin tests and specific IgE. Four patients out of 73 had a
      positive patch tests to at least one penicillin reagent and imipenem-cilastatin
      showing cross-reactivity. Sixty-four patients underwent the imipenem-cilastatin
      intramuscular test dosing and none of them had a clinical reaction. CONCLUSIONS:
      Our rate of cross-reactivity between imipenem-cilastatin and other beta-lactams
      was 5.5%. This result is different from previous findings and this may be
      explained by the fact that we investigated patients with cell-mediated allergy to
      beta-lactams. Patients with cell-mediated allergy to beta-lactams should undergo
      patch tests and a tolerance challenge test before treatment with imipenem
      cilastatin.

PMID- 19392999
TI  - Immediate allergic reaction to atropine in ophthalmic solution confirmed by
      basophil activation test.

PMID- 19393000
TI  - The size of the disease relevant IgE antibody fraction in relation to 'total-IgE'
      predicts the efficacy of anti-IgE (Xolair) treatment.
AB  - BACKGROUND: Some patients with allergic asthma treated with anti-IgE (Xolair) do
      not become symptom free. Better criteria for response assessment than allergy
      skin tests or IgE determination are needed. The impact of the size of the disease
      relevant allergen-specific IgE antibody fraction, i.e. the percentage of IgE
      antibody of total IgE, was evaluated in cat allergic patients treated with the
      recommended doses of Xolair. Results were measured as changes in basophil
      allergen threshold sensitivity (CD-sens). METHODS: In a double-blind placebo
      controlled trial 20 patients with a high (>3.8%) and 18 with a low (<1%)
      percentage of IgE antibodies to cat were given Xolair for 16 weeks and the change
      in CD-sens was compared to 11 and 10 patients, respectively, in each group
      receiving placebo. RESULTS: The CD-sens dropped significantly in both the high (P
      < 0.001) and low (P < 0.001) group on Xolair but did not change significantly
      after placebo. For Xolair-treated patients, at the end of the trial there was a
      highly significant (P < 0.001) difference in CD-sens between the high group,
      where no patients, and the low group, where 13/18 patients, had become negative.
      CONCLUSIONS: The currently recommended doses of Xolair very efficiently eliminate
      IgE antibodies if the IgE antibody fraction is <1% of total IgE but has not
      enough effect on allergen sensitivity if the fraction is >3-4%. Further studies
      will show if increased doses of Xolair would help also these patients, who seem
      to represent about 1/3 of the patient population.

PMID- 19393001
TI  - The Third ISN Special Neurochemistry Conference--8th International Meeting on
      Brain Energy Metabolism--'Neurodegeneration and Regeneration'.

PMID- 19393002
TI  - Transcranial flavoprotein fluorescence imaging of mouse cortical activity and
      plasticity.
AB  - Endogenous fluorescence signals derived from mitochondria reflect activity
      dependent changes in brain metabolism and may be exploited in functional brain
      imaging. Endogenous flavoprotein fluorescence imaging in mice is especially
      important because many genetically manipulated strains of mice are available and
      the transparent skull of mice allows transcranial fluorescence imaging of
      cortical activities. In the primary sensory areas of mice, cortical activities
      and experience-dependent plasticity have been investigated using transcranial
      fluorescence imaging. Furthermore, differential imaging, based on stimulus
      specificity of cortical areas, distinguished activities in higher visual areas
      around the primary visual cortex from those in primary visual cortex. The
      combination of transcranial fluorescence imaging with the suppression of cortical
      activities using photobleaching of flavoproteins is expected to aid in
      elucidating the roles of sensory cortices including higher areas in mice.

PMID- 19393003
TI  - What learning in day-old chickens can teach a neurochemist: focus on astrocyte
      metabolism.
AB  - The learning process sets in motion a prolonged, reproducible, and complicated
      pattern of brain activation, which provides information about biochemical
      reactions in activated brain. Study of this pattern during one-trial aversive
      bead discrimination in day-old chick is facilitated by precise timing of
      sequential metabolic events occurring between a 10-s learning period, in which
      the chicks learn to associate a red bead with aversive taste, and memory
      consolidation, indicated by unwillingness to peck at untainted red beads while
      freely pecking at corresponding blue beads. Inhibition of learning by metabolic
      inhibitors and restoration of memory by specific substrates at specific times
      allow determination of specific metabolic events and their neuronal or astrocytic
      localization. Downstream metabolism of glycogen and of glucose to
      pyruvate/lactate is segregated into separate pools. Glucose metabolism via
      pyruvate dehydrogenation provides energy in both neurons and astrocytes and may
      include gap junction-mediated lactate transport into astrocytes. A key role is
      played by glycogenolysis, stimulated by beta2-adrenergic and/or 5-HT2-receptor
      stimulation along with alpha2-adrenergic stimulation of glycogen synthesis. The
      importance of glycogen reflects that it selectively supports de novo synthesis of
      transmitter glutamate by combined pyruvate dehydrogenation and carboxylation in
      astrocytes.

PMID- 19393005
TI  - Direct measurement of oxidative metabolism in the living brain by microdialysis:
      a review.
AB  - This review summarizes microdialysis studies that address the question of which
      compounds serve as energy sources in the brain. Microdialysis was used to
      introduce 14C-labeled glucose, lactate, pyruvate, glutamate, glutamine, and
      acetate into the interstitial fluid of the brain to observe their metabolism to
      14CO2. Although glucose uptake from the systemic system supplies the carbon
      source for these compounds, compounds synthesized from glucose by the brain are
      subject to recycling including complete metabolism to CO2. Therefore, the brain
      utilizes multiple compounds in its domain to provide the energy needed to fulfill
      its function. The physiological conditions controlling metabolism and the
      contribution of compartmentation into different brain regions, cell types, and
      subcellular spaces are still unresolved. The aconitase inhibitor fluorocitrate,
      with a lower inhibition threshold in glial cells, was used to identify the
      proportion of lactate and glucose that was oxidized in glial cells versus
      neurons. The fluorocitrate data suggest that glial and neuronal cells are capable
      of utilizing both lactate and glucose for energy metabolism.

PMID- 19393004
TI  - AMPK in the brain: its roles in energy balance and neuroprotection.
AB  - Adenosine monophosphate-activated protein kinase (AMPK) senses metabolic stress
      and integrates diverse physiological signals to restore energy balance. Multiple
      functions are indicated for AMPK in the CNS. While all neurons sense their own
      energy status, some integrate neuro-humoral signals to assess organismal energy
      balance. A variety of disease states may involve AMPK, so determining the
      underlying mechanisms is important. We review the impact of altered AMPK activity
      under physiological (hunger, satiety) and pathophysiological (stroke) conditions,
      as well as therapeutic manipulations of AMPK that may improve energy balance.

PMID- 19393006
TI  - Exchange-mediated dilution of brain lactate specific activity: implications for
      the origin of glutamate dilution and the contributions of glutamine dilution and
      other pathways.
AB  - The magnitude of metabolic activation is greatly underestimated in
      autoradiographic studies using [1- or 6-14C]glucose compared to parallel assays
      with [14C]deoxyglucose indicating that most of the label corresponding to the
      additional [14C]glucose consumed during activation compared to rest is quickly
      released from activated structures. Label could be lost by net release of
      [14C]lactate from brain or via lactate exchange between blood and brain. These
      possibilities were distinguished by comparison of glucose and lactate specific
      activities in arterial blood and brain before, during, and after generalized
      sensory stimulation and during spreading cortical depression. Over a wide range
      of brain lactate concentrations, lactate specific activity was close to the
      theoretical maximum, i.e. half that of [6-14C]glucose, indicating that exchange
      mediated dilution of lactate is negligible and that efflux of [14C]lactate
      probably accounts for most of the label loss. Low lactate dilution also indicates
      that dilution of glutamate C4 fractional enrichment in [13C]glucose studies,
      currently ascribed predominantly to lactate exchange, arises from other
      unidentified pathways or factors. Alternative explanations for glutamate dilution
      (presented in Supporting Information) include poorly labeled amino acid pools and
      oxidative metabolism of minor substrates in astrocytes to first dilute the
      astrocytic glutamine pool, followed by dilution of glutamate via glutamate
      glutamine cycling.

PMID- 19393007
TI  - The rate-limiting step for glucose transport into the hypothalamus is across the
      blood-hypothalamus interface.
AB  - Specialized glucosensing neurons are present in the hypothalamus, some of which
      neighbor the median eminence, where the blood-brain barrier has been reported
      leaky. A leaky blood-brain barrier implies high tissue glucose levels and
      obviates a role for endothelial glucose transporters in the control of
      hypothalamic glucose concentration, important in understanding the mechanisms of
      glucose sensing We therefore addressed the question of blood-brain barrier
      integrity at the hypothalamus for glucose transport by examining the brain tissue
      to-plasma glucose ratio in the hypothalamus relative to other brain regions. We
      also examined glycogenolysis in hypothalamus because its occurrence is unlikely
      in the potential absence of a hypothalamus-blood interface. Across all regions
      the concentration of glucose was comparable at a given plasma glucose
      concentration and was a near linear function of plasma glucose. At steady-state,
      hypothalamic glucose concentration was similar to the extracellular hypothalamic
      glucose concentration reported by others. Hypothalamic glycogen fell at a rate of
      approximately 1.5 micromol/g/h and remained present in substantial amounts. We
      conclude for the hypothalamus, a putative primary site of brain glucose sensing
      that: the rate-limiting step for glucose transport into brain cells is at the
      blood-hypothalamus interface, and that glycogenolysis is consistent with a
      substantial blood -to- intracellular glucose concentration gradient.

PMID- 19393008
TI  - Acetate transport and utilization in the rat brain.
AB  - Acetate, a glial-specific substrate, is an attractive alternative to glucose for
      the study of neuronal-glial interactions. The present study investigates the
      kinetics of acetate uptake and utilization in the rat brain in vivo during
      infusion of [2-13C]acetate using NMR spectroscopy. When plasma acetate
      concentration was increased, the rate of brain acetate utilization (CMR(ace))
      increased progressively and reached close to saturation for plasma acetate
      concentration > 2-3 mM, whereas brain acetate concentration continued to
      increase. The Michaelis-Menten constant for brain acetate utilization (K(M)(util)
      = 0.01 +/- 0.14 mM) was much smaller than for acetate transport through the blood
      brain barrier (BBB) (K(M)(t) = 4.18 +/- 0.83 mM). The maximum transport capacity
      of acetate through the BBB (V(max)(t) = 0.96 +/- 0.18 micromol/g/min) was nearly
      twofold higher than the maximum rate of brain acetate utilization (V(max)(util) =
      0.50 +/- 0.08 micromol/g/min). We conclude that, under our experimental
      conditions, brain acetate utilization is saturated when plasma acetate
      concentrations increase above 2-3 mM. At such high plasma acetate concentration,
      the rate-limiting step for glial acetate metabolism is not the BBB, but occurs
      after entry of acetate into the brain.

PMID- 19393009
TI  - The in vivo neuron-to-astrocyte lactate shuttle in human brain: evidence from
      modeling of measured lactate levels during visual stimulation.
AB  - Functional magnetic resonance spectroscopy (fMRS) allows the non-invasive
      measurement of metabolite concentrations in the human brain, including changes
      induced by variations in neurotransmission activity. However, the limited spatial
      and temporal resolution of fMRS does not allow specific measurements of
      metabolites in different cell types. Thus, the analysis of fMRS data in the
      context of compartmentalized metabolism requires the formulation and application
      of mathematical models. In the present study we utilized the mathematical model
      introduced by Simpson et al. (2007) to gain insights into compartmentalized
      metabolism in vivo from the fMRS data obtained in humans at ultra high magnetic
      field by Mangia et al. (2007a). This model simulates brain glucose and lactate
      levels in a theoretical cortical slice. Using experimentally determined
      concentrations and catalytic activities for the respective transporter proteins,
      we calculate inflow and export of glucose and lactate in endothelium, astrocytes,
      and neurons. We then vary neuronal and astrocytic glucose and lactate utilization
      capacities until close correspondence is observed between in vivo and simulated
      glucose and lactate levels. The results of the simulations indicate that, when
      literature values of glucose transport capacity are utilized, the fMRS data are
      consistent with export of lactate by neurons and import of lactate by astrocytes,
      a mechanism that can be referred to as a neuron-to-astrocyte lactate shuttle. A
      shuttle of lactate from astrocytes to neurons could be simulated, but this
      required the astrocytic glucose transport capacity to be increased by 12-fold,
      and required that neurons not respond to activation with increased glycolysis,
      two conditions that are not supported by current literature.

PMID- 19393010
TI  - The turnover of the H3 deuterons from (2-13C) glutamate and (2-13C) glutamine
      reveals subcellular trafficking in the brain of partially deuterated rats.
AB  - We investigated by 13C NMR the turnover of the H3 deuterons of (2-13C) glutamate
      and (2-13C) glutamine in the brain of partially deuterated rats. Adult animals
      (150-200 g) fed ad libitum received 50% 2H2O or tap water 9 days before infusing
      (1-13C) glucose or (2-13C) acetate for 5, 10, 15, 30, 60, or 90 min. The brains
      were then funnel-frozen and acid extracts were prepared and analyzed by high
      resolution 13C NMR. The deuteration of one or the two H3 hydrogens of (2-13C)
      glutamate or glutamine resulted in single (-0.07 ppm) or double (-0.14 ppm)
      isotopic shifts upfield of the corresponding C2 perprotonated resonance,
      demonstrating two sequential deuteration steps. The faster monodeuteration
      generated 3R or 3S (2-13C, 3-2H) glutamate or glutamine through the alternate
      activities of cerebral aconitase or isocitrate dehydrogenase, respectively. The
      slower process produced bideuterated (2-13C, 3,3'-2H2) glutamate or glutamine
      through the consecutive activity of both enzymes. The kinetics of deuteration was
      fitted to a Michaelis-Menten model including the apparent K(m)' and Vmax' values
      for the observed deuterations. Our results revealed different kinetic constants
      for the alternate and consecutive deuterations, suggesting that these processes
      were caused by the different cytosolic or mitochondrial isoforms of aconitase and
      isocitrate dehydrogenase, respectively. The deuterations of (2-13C) glutamate or
      glutamine followed also different kinetics from (1-13C) glucose or (2-13C)
      acetate, revealing distinct deuteration environments in the neuronal or glial
      compartments.

PMID- 19393011
TI  - Cerebral oxygen demand for short-lived and steady-state events.
AB  - Because of the importance of oxidative energetics for cerebral function,
      extraction of oxygen consumption (CMR(O2)) from blood oxygenation level-dependent
      (BOLD) signal using multi-modal measurements of blood flow (CBF) and volume (CBV)
      has become an accepted functional magnetic resonance imaging (fMRI) technique.
      This approach, termed calibrated fMRI, is based on a biophysical model which
      describes tissue oxygen extraction at steady-state. A problem encountered for
      calculating dynamic CMR(O2) relates to concerns whether the conventional BOLD
      model can be applied transiently. In particular, it is unclear whether
      calculation of CMR(O2) differs between short and long stimuli. Linearity was
      experimentally demonstrated between BOLD-related components and neural activity,
      thereby making it possible to use calibrated fMRI in a dynamic manner. We used
      multi-modal fMRI and electrophysiology, in alpha-chloralose anesthetized rats
      during forepaw stimulation to show that respective transfer functions (of BOLD,
      CBV, CBF) generated by deconvolution with neural activity are time invariant, for
      events in the millisecond to minute range. These results allowed extraction of a
      significant component of the BOLD signal that can be ascribed to CMR(O2)
      transients. We discuss the importance of minimizing residual signal, represented
      by the difference between modeled and raw signals, in convolution analysis of
      multi-modal signals.

PMID- 19393012
TI  - Functional significance of brain glycogen in sustaining glutamatergic
      neurotransmission.
AB  - The involvement of brain glycogen in sustaining neuronal activity has previously
      been demonstrated. However, to what extent energy derived from glycogen is
      consumed by astrocytes themselves or is transferred to the neurons in the form of
      lactate for oxidative metabolism to proceed is at present unclear. The
      significance of glycogen in fueling glutamate uptake into astrocytes was
      specifically addressed in cultured astrocytes. Moreover, the objective was to
      elucidate whether glycogen derived energy is important for maintaining
      glutamatergic neurotransmission, induced by repetitive exposure to NMDA in co
      cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown
      that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen
      degradation was inhibited irrespective of the presence of glucose, signifying
      that energy derived from glycogen degradation is important for the astrocytic
      compartment. By inhibiting glycogen degradation in co-cultures it was evident
      that glycogen provides energy to sustain glutamatergic neurotransmission, i.e.
      release and uptake of glutamate. The relocation of glycogen derived lactate to
      the neuronal compartment was investigated by employing d-lactate, a competitive
      substrate for the monocarboxylate transporters. Neurotransmitter release was
      affected by the presence of d-lactate indicating that glycogen derived energy is
      important not only in the astrocytic but also in the neuronal compartment.

PMID- 19393013
TI  - Neuronal glucose but not lactate utilization is positively correlated with NMDA
      induced neurotransmission and fluctuations in cytosolic Ca2+ levels.
AB  - Although the brain utilizes glucose for energy production, individual brain cells
      may to some extent utilize substrates derived from glucose. Thus, it has been
      suggested that neurons consume extracellular lactate during synaptic activity.
      However, the precise role of lactate for fueling neuronal activity is still
      poorly understood. Recently, we demonstrated that glucose metabolism is up
      regulated in cultured glutamatergic neurons during neurotransmission whereas that
      of lactate is not. Here, we show that utilization of glucose but not lactate
      correlates with NMDA-induced neurotransmitter glutamate release in cultured
      cerebellar neurons from mice. Pulses of NMDA at 30, 100, and 300 microM, leading
      to a progressive increase in both cytosolic [Ca2+] and release of glutamate,
      increased uptake and metabolism of glucose but not that of lactate as evidenced
      by mass spectrometric measurement of 13C incorporation into intracellular
      glutamate. In this manuscript, a cascade of events for the preferential neuronal
      utilization of glucose during neurotransmission is suggested and discussed in
      relation to our current understanding of neuronal energy metabolism.

PMID- 19393014
TI  - Kinetic validation of 6-NBDG as a probe for the glucose transporter GLUT1 in
      astrocytes.
AB  - In recent years, the use of fluorescent glucose analogs has allowed the study of
      rapid transport modulation in heterogeneous cell cultures and complex tissues.
      However, the kinetic behavior of these tracers is not conventional. For instance,
      the fluorescent glucose analog 6-NBDG permeates the cell 50-100 times slower than
      glucose but the uptake of 6-NBDG is almost insensitive to glucose, an observation
      that casts doubts as to the specificity of the uptake pathway. To investigate
      this apparent anomaly in cultured astrocytes, which are rich in the glucose
      transporter GLUT1, we first estimated the kinetic parameters of 6-NBDG uptake,
      which were then incorporated into the kinetic model of GLUT1. The main outcome of
      the analysis was that 6-NBDG binds to GLUT1 with 300 times higher affinity than
      glucose, which explains why its uptake is not efficiently displaced by glucose.
      The high binding affinity of 6-NBDG also explains why cytochalasin B is less
      effective at inhibiting 6-NBDG uptake than at inhibiting glucose uptake. We
      conclude that 6-NBDG, used at low concentrations, permeates into astrocytes
      chiefly through GLUT1, and advise that the exofacial GLUT1 inhibitor 4,6
      ethylidine-D-glucose be used, instead of glucose, as the tool of choice to
      confirm the specificity of 6-NBDG uptake.

PMID- 19393015
TI  - Mitochondrial glutathione uptake: characterization in isolated brain mitochondria
      and astrocytes in culture.
AB  - Glutathione in the mitochondria is an important determinant of cellular responses
      to oxidative stress. Mitochondrial glutathione is maintained by uptake from the
      cytosol, a process that has been little studied in brain cells. In the present
      study, measurements using isolated rat brain mitochondria showed a rapid uptake
      of [3H]-glutathione that was strongly influenced by the mitochondrial glutathione
      content. [3H]-glutathione incorporated into the mitochondria was not rapidly
      released. Uptake was inhibited by substrates and inhibitors for several known
      mitochondrial anion transporters. Citrate, isocitrate and benzene-1,2,3
      tricarboxylate were particularly effective inhibitors, suggesting a possible role
      for a tricarboxylate carrier in the glutathione transport. The properties of
      uptake differed greatly from those reported previously for mitochondria from
      kidney and liver. In astrocytes in primary culture, diethylmaleate or hydrogen
      peroxide treatment resulted in depletion of cytosolic and mitochondrial
      glutathione. The pattern of restoration of glutathione content in the presence of
      glutathione precursors following treatment with diethylmaleate was consistent
      with uptake into mitochondria being controlled primarily by the glutathione
      gradient between the cytosol and mitochondria. However, following hydrogen
      peroxide treatment, recovery of glutathione in the mitochondria initially
      preceded comparable proportional restoration in the cytosol, suggesting the
      possibility of additional controls on glutathione uptake in some conditions.

PMID- 19393016
TI  - Now I know my ABC. A systems neurochemistry and functional metabolomic approach
      to understanding the GABAergic system.
AB  - Here, we describe use of a reductionist brain model, the brain tissue slice, to
      generate snapshots of functional metabolism in response to a pharmacological
      (GABAergic) perturbation. Tissue slices prepared from Guinea pig cerebral cortex
      were incubated for 1 h in the presence of [3-13C]-pyruvate and ligands with
      affinity for GABA receptors. The resultant patterns of 13C flux and metabolite
      levels were measured by 13C/1H NMR spectroscopy, generating 'metabolic
      fingerprints' for each ligand. Effects of agonists and effectors at GABA
      receptors (A, B, and C types) were examined, compared to those of exogenous GABA
      and evaluated using multivariate statistical models. Data clusterings did not
      directly correlate with GABA receptor types but produced at least five distinct
      groups ranked according to their affinity for GABA. As our experimental model
      retains, to a large extent, the structure and function of normal brain tissue,
      the generated database can be used to assess GABAergic ligands and make unique
      inferences relevant to their modes of action in brain.

PMID- 19393017
TI  - Differential gene expression in LPS/IFNgamma activated microglia and macrophages:
      in vitro versus in vivo.
AB  - Two different macrophage populations contribute to CNS neuroinflammation: CNS
      resident microglia and CNS-infiltrating peripheral macrophages. Markers
      distinguishing these two populations in tissue sections have not been identified.
      Therefore, we compared gene expression between LPS
      (lipopolysaccharide)/interferon (IFN)gamma-treated microglia from neonatal mixed
      glial cultures and similarly treated peritoneal macrophages. Fifteen molecules
      were identified by quantative PCR (qPCR) as being enriched from 2-fold to 250
      fold in cultured neonatal microglia when compared with peritoneal macrophages.
      Only three of these molecules (C1qA, Trem2, and CXCL14) were found by qPCR to be
      also enriched in adult microglia isolated from LPS/IFNgamma-injected CNS when
      compared with infiltrating peripheral macrophages from the same CNS. The
      discrepancy between the in vitro and in vivo qPCR data sets was primarily because
      of induced expression of the 'microglial' molecules (such as the tolerance
      associated transcript, Tmem176b) in CNS-infiltrating macrophages. Bioinformatic
      analysis of the approximately 19000 mRNAs detected by TOGA gene profiling
      confirmed that LPS/IFNgamma-activated microglia isolated from adult CNS displayed
      greater similarity in total gene expression to CNS-infiltrating macrophages than
      to microglia isolated from unmanipulated healthy adult CNS. In situ hybridization
      analysis revealed that nearly all microglia expressed high levels of C1qA, while
      subsets of microglia expressed Trem2 and CXCL14. Expression of C1qA and Trem2 was
      limited to microglia, while large numbers of GABA+ neurons expressed CXCL14.
      These data suggest that (i) CNS-resident microglia are heterogeneous and thus a
      universal microglia-specific marker may not exist; (ii) the CNS micro-environment
      plays significant roles in determining the phenotypes of both CNS-resident
      microglia and CNS-infiltrating macrophages; (iii) the CNS microenvironment may
      contribute to immune privilege by inducing macrophage expression of anti
      inflammatory molecules.

PMID- 19393018
TI  - CD36: a multi-modal target for acute stroke therapy.
AB  - A role for CD36 in the pathogenesis of atherosclerosis, inflammation and lipid
      metabolism has been well-documented. However, little is known about the role of
      CD36 in cerebral ischemia. The intent of this review is to develop the concept
      that CD36, whose functions have been implicated in other pathological events, is
      a prototypic inflammatory receptor that contributes to the pathogenesis of
      cerebral ischemia. The importance of CD36 as a treatment target is indicated by
      the fact that many treatment strategies that are effective in experimental models
      of stroke exhibit little or no efficacy in clinical trials. The failure of
      clinical trials may be due to the use of animal models of stroke that do not
      reflect traditional risk factors for stroke in humans. The discussion will be
      focused on two risk factors, hyperlipidemia and diabetes, that modulate CD36
      responses. Blocking the expression and function of CD36 by pharmacological or
      genetic means will provide insight not only toward identifying CD36 as a novel
      molecular target but also for developing effective therapeutic strategies to
      treat stroke victims. More importantly, coupling clinically relevant conditions
      with CD36-mediated ischemic injury may provide an appropriate animal model
      paradigm and develop a scientific understanding that could lead to clinical
      translational studies involving human subjects.

PMID- 19393019
TI  - Oxidative stress and mitochondrial dysfunction as determinants of ischemic
      neuronal death and survival.
AB  - Mitochondria are the powerhouse of the cell. Their primary physiological function
      is to generate adenosine triphosphate through oxidative phosphorylation via the
      electron transport chain. Reactive oxygen species generated from mitochondria
      have been implicated in acute brain injuries such as stroke and
      neurodegeneration. Recent studies have shown that mitochondrially-formed oxidants
      are mediators of molecular signaling, which is implicated in the mitochondria
      dependent apoptotic pathway that involves pro- and antiapoptotic protein binding,
      the release of cytochrome c, and transcription-independent p53 signaling, leading
      to neuronal death. Oxidative stress and the redox state of ischemic neurons are
      also implicated in the signaling pathway that involves phosphatidylinositol 3
      kinase/Akt and downstream signaling, which lead to neuronal survival. Genetically
      modified mice or rats that over-express or are deficient in superoxide dismutase
      have provided strong evidence in support of the role of mitochondrial dysfunction
      and oxidative stress as determinants of neuronal death/survival after stroke and
      neurodegeneration.

PMID- 19393020
TI  - Synaptic and extrasynaptic GABA transporters as targets for anti-epileptic drugs.
AB  - Inhibition of the GABA transporter subtype GAT1 by the clinically available anti
      epileptic drug tiagabine has proven to be an effective strategy for the treatment
      of some patients with partial seizures. In 2005, the investigational drug EF1502
      was described as possessing activity at both GAT1 and BGT-1. When combined with
      the GAT1 selective inhibitor tiagabine, EF1502 was found to possess a synergistic
      anti-convulsant action in the Frings audiogenic seizure-susceptible mouse model
      of reflex epilepsy. This effect was subsequently attributed to inhibition of BGT
      1. In this study, the anti-convulsant effect of the GAT2/3 inhibitor SNAP-5114
      was assessed in the Frings audiogenic seizure-susceptible mouse alone, and in
      combination with tiagabine and EF1502. The results showed that SNAP-5114 produced
      a synergistic anti-convulsant effect in combination with EF1502 but not when used
      in combination with tiagabine. These findings support anatomical evidence that
      GAT2/3 are most likely located at the synapse in close proximity to GAT1; whereas
      BGT-1 is located some distance away from the synapse and GAT1 and GAT2/3. Lastly,
      EF1502 and tiagabine were evaluated alone, and in combination, in the corneal
      kindled mouse model of partial epilepsy. The results of this evaluation provide
      further evidence in support of a role for BGT-1 in the control of seizure
      activity. In addition, they suggest that the combined inhibition of GAT1 and BGT
      1 may afford some advantage over inhibiting either transporter alone.

PMID- 19393021
TI  - Contributions of Ca2+ and Zn2+ to spreading depression-like events and neuronal
      injury.
AB  - The phenomenon of spreading depression (SD) involves waves of profound neuronal
      and glial depolarization that spread throughout brain tissue. Under many
      conditions, tissue recovers full function after SD has occurred, but SD-like
      events are also associated with spread of injury following ischemia or trauma.
      Initial large cytosolic Ca2+ increases accompany all forms of SD, but
      persistently elevated Ca2+ loading is likely responsible for neuronal injury
      following SD in tissues where metabolic capacity is insufficient to restore ionic
      gradients. Ca2+ channels are also involved in the propagation of SD, but the
      channel subtypes and cation fluxes differ significantly when SD is triggered by
      different types of stimuli. Ca2+ influx via P/Q type channels is important for SD
      generated by localized application of high K+ solutions. In contrast, SD-like
      events recorded in in vitro ischemia models are not usually prevented by Ca2+
      removal, but under some conditions, Zn2+ influx via L-type channels contributes
      to SD initiation. This review addresses different roles of Ca2+ in the initiation
      and consequences of SD, and discusses recent evidence that selective chelation of
      Zn2+ can be sufficient to prevent SD under circumstances that may have relevance
      for ischemic injury.

PMID- 19393022
TI  - The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's
      disease.
AB  - Mitochondria play critical roles in neuronal function and almost all aspects of
      mitochondrial function are altered in Alzheimer neurons. Emerging evidence shows
      that mitochondria are dynamic organelles that undergo continuous fission and
      fusion, the balance of which not only controls mitochondrial morphology and
      number, but also regulates mitochondrial function and distribution. In this
      review, after a brief overview of the basic mechanisms involved in the regulation
      of mitochondrial fission and fusion and how mitochondrial dynamics affects
      mitochondrial function, we will discuss in detail our and others' recent work
      demonstrating abnormal mitochondrial morphology and distribution in Alzheimer's
      disease (AD) models and how these abnormalities may contribute to mitochondrial
      and synaptic dysfunction in AD. We propose that abnormal mitochondrial dynamics
      plays a key role in causing the dysfunction of mitochondria that ultimately
      damage AD neurons.

PMID- 19393024
TI  - Mutations in human GLUD2 glutamate dehydrogenase affecting basal activity and
      regulation.
AB  - Glutamate dehydrogenase (GDH) in human exists in GLUD1 and GLUD2 gene-encoded
      isoforms (hGDH1 and hGDH2, respectively), differing in their regulation and
      tissue expression pattern. Whereas hGDH1 is subject to GTP control, hGDH2 uses
      for its regulation, a novel molecular mechanism not requiring GTP. This is based
      on the ability of hGDH2 to maintain a baseline activity of <10% of its capacity
      subject to full activation by rising ADP/L-leucine levels. Here we studied
      further the molecular mechanisms regulating hGDH2 function by creating and
      analyzing hGDH2 mutants harboring single amino acid substitutions in the
      regulatory domain (antenna, pivot helix) of the protein. Five hGDH2 mutants were
      obtained: two with an amino acid change (Gln441Arg, Ser445Leu) in the antenna,
      two (Lys450Glu, His454Tyr) in the pivot helix, and one (Ser448Pro) in the
      junction between the two structures. Functional analyses revealed that, while the
      antenna mutations increased basal enzyme activity without affecting its
      allosteric properties, the pivot helix mutations drastically reduced basal
      activity and impaired enzyme regulation. On the other hand, the Ser448Pro
      mutation reduced basal activity but did not alter allosteric regulation. Also,
      compared with wild-type hGDH2, the antenna mutants were relatively thermostable,
      whereas the pivot helix mutants were extremely heat labile. Hence, the present
      data further our understanding of the molecular mechanisms involved in the
      function and stability of hGDH2, an enzyme thought to be of importance for nerve
      tissue biology.

PMID- 19393023
TI  - Transglutaminases and neurodegeneration.
AB  - Transglutaminases (TGs) are Ca2+-dependent enzymes that catalyze a variety of
      modifications of glutaminyl (Q) residues. In the brain, these modifications
      include the covalent attachment of a number of amine-bearing compounds, including
      lysyl (K) residues and polyamines, which serve to either regulate enzyme activity
      or attach the TG substrates to biological matrices. Aberrant TG activity is
      thought to contribute to Alzheimer disease, Parkinson disease, Huntington
      disease, and supranuclear palsy. Strategies designed to interfere with TG
      activity have some benefit in animal models of Huntington and Parkinson diseases.
      The following review summarizes the involvement of TGs in neurodegenerative
      diseases and discusses the possible use of selective inhibitors as therapeutic
      agents in these diseases.

PMID- 19393025
TI  - Acute changes in intermediary metabolism in cerebellum and contralateral
      hemisphere following middle cerebral artery occlusion in rat.
AB  - Focal ischemia leads to functional deafferentation of regions connected to the
      ischemic area via fiber tracts. Using i.v. administration of 13C-labeled glucose
      and acetate combined with ex vivo 13C MR spectroscopy and HPLC of brain extracts
      we identify the effect of middle cerebral artery occlusion (MCAO) on
      neurotransmitter synthesis and turnover, and on neuro-astrocytic interactions in
      the non-ischemic cerebellum and in contralesional lateral caudoputamen plus lower
      parietal cortex (LPC), and upper frontoparietal cortex (UFPCx) in the rat after
      30, 60, 120 and 240 min of ischemia. In all regions, there was a significant
      persisting loss of glutamate, and in LCP and UFPCx also of glutamine, but only in
      LCP was GABA reduced at all times. Metabolism and blood flow were uncoupled in
      all regions. In cerebellum, glucose metabolism as well as utilization of
      intermediates derived from astrocytic tricarboxylic acid cycle activity were
      significantly decreased at all times in both glutamatergic and GABAergic neurons.
      In LCP and UFPCx, there were normal or increased enrichment in glutamate and GABA
      from glucose. Glutamate derived from astrocytic acetate metabolism was increased,
      but GABA synthesis from acetate was initially impaired. The results showed that
      both the type of afferent connection, i.e., glutamatergic and/or GABAergic, and
      local cytoarchitecture, determined the effect MCAO had on metabolic activity in
      the non-ischemic regions. In conclusion, it was primarily excitatory input into
      non-ischemic regions that was affected by MCAO, perhaps enabling resetting of the
      excitatory/inhibitory balance, aiding reshaping of the receptive fields and thus
      facilitating recovery.

PMID- 19393026
TI  - Ischemia activates JNK/c-Jun/AP-1 pathway to up-regulate 14-3-3gamma in
      astrocyte.
AB  - Ischemia occurs in the brain as the result of stroke and other related injuries
      and few therapies are effective. If more is understood then potential treatments
      could be investigated. It was previously reported that 14-3-3gamma could be up
      regulated by ischemia in astrocyte to protect cells from ischemia-induced
      apoptosis. In this study, we attempted to uncover the mechanism responsible for
      this 14-3-3gamma up-regulation in primary culture of astrocytes under ischemic
      like conditions. It was found that in vitro ischemia may activate PI3K/Akt and
      MAPK signaling pathways. Astrocyte cultures were treated with LY294002 (PI3K
      inhibitor), U0126 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK
      inhibitor). Only SP600125 could inhibit the ischemia-induced 14-3-3gamma up
      regulation in astrocytes. At the same time, we observed an ischemia-induced
      nuclear translocation of p-c-Jun, a major downstream component of JNK. Inhibition
      of AP-1 with curcumin also inhibited 14-3-3gamma up-regulation indicating that
      ischemia-induced up-regulation of 14-3-3gamma in astrocyte involves activation of
      the JNK/p-c-Jun/AP-1 pathway.

PMID- 19393028
TI  - GABAergic striatal neurons exhibit caspase-independent, mitochondrially mediated
      programmed cell death.
AB  - GABAergic striatal neurons are compromised in basal ganglia pathologies and we
      analysed how insult nature determined their patterns of injury and recruitment of
      the intrinsic mitochondrial pathway during programmed cell death (PCD). Stressors
      affecting targets implicated in striatal neurodegeneration [3
      morpholinylsydnoneimine (SIN-1), 3-nitropropionic acid (3-NP), NMDA, 3,5
      dihydroxyphenylglycine (DHPG), and staurosporine (STS)] were compared in cultured
      GABAergic neurons from murine striatum by analyzing the progression of injury and
      its correlation with mitochondrial involvement, the redistribution of
      intermembrane space (IMS) proteins, and patterns of protease activation.
      Stressors produced PCD exhibiting slow-onset kinetics with time-dependent annexin
      V labeling and eventual DNA fragmentation. IMS proteins including cytochrome c
      were differentially distributed, although stressors except STS produced early
      redistribution of apoptosis-inducing factor and Omi, suggestive of early
      recruitment of both caspase-dependent and caspase-independent signaling. In
      general, Bax mobilization to mitochondria appeared to promote IMS protein
      redistribution. Caspase 3 activation was prominent after STS, whereas NMDA and
      SIN-1 produced mainly calpain activation, and 3-NP and DHPG elicited a mixed
      profile of protease activation. PCD and redistribution of IMS proteins in
      striatal GABAergic neurons were canonical and insult-dependent, reflecting
      differential interplay between the caspase cascade and alternate cell death
      pathways.

PMID- 19393027
TI  - Delayed cerebral oxidative glucose metabolism after traumatic brain injury in
      young rats.
AB  - Traumatic brain injury (TBI) results in a cerebral metabolic crisis that
      contributes to poor neurologic outcome. The aim of this study was to characterize
      changes in oxidative glucose metabolism in early periods after injury in the
      brains of immature animals. At 5 h after controlled cortical impact TBI or sham
      surgery to the left cortex, 21-22 day old rats were injected intraperitoneally
      with [1,6-13C]glucose and brains removed 15, 30 and 60 min later and studied by
      ex vivo 13C-NMR spectroscopy. Oxidative metabolism, determined by incorporation
      of 13C into glutamate, glutamine and GABA over 15-60 min, was significantly
      delayed in both hemispheres of brain from TBI rats. The most striking delay was
      in labeling of the C4 position of glutamate from neuronal metabolism of glucose
      in the injured, ipsilateral hemisphere which peaked at 60 min, compared with the
      contralateral and sham-operated brains, where metabolism peaked at 30 and 15 min,
      respectively. Our findings indicate that (i) neuronal-specific oxidative
      metabolism of glucose at 5-6 h after TBI is delayed in both injured and
      contralateral sides compared with sham brain; (ii) labeling from metabolism of
      glucose via the pyruvate carboxylase pathway in astrocytes was also initially
      delayed in both sides of TBI brain compared with sham brain; (iii) despite this
      delayed incorporation, at 6 h after TBI, both sides of the brain showed apparent
      increased neuronal and glial metabolism, reflecting accumulation of labeled
      metabolites, suggesting impaired malate aspartate shuttle activity. The presence
      of delayed metabolism, followed by accumulation of labeled compounds is evidence
      of severe alterations in homeostasis that could impair mitochondrial metabolism
      in both ipsilateral and contralateral sides of brain after TBI. However, ongoing
      oxidative metabolism in mitochondria in injured brain suggests that there is a
      window of opportunity for therapeutic intervention up to at least 6 h after
      injury.

PMID- 19393029
TI  - The ketogenic diet has no effect on the expression of spike-and-wave discharges
      and nutrient transporters in genetic absence epilepsy rats from Strasbourg.
AB  - The genetic absence epilepsy rat from Strasbourg is considered an isomorphic,
      predictive, and homologous model of typical childhood absence epilepsy. It is
      characterized by the expression of spike-and-wave discharges (SWDs) in the
      thalamus and cortex. The ketogenic diet (KD) is successfully used in humans and
      animals with various types of seizures, but was not effective in children with
      intractable atypical absence epilepsy. Here, we studied its potential impact on
      the occurrence of SWDs in genetic absence epilepsy rat from Strasbourg. Rats were
      fed the KD for 3 weeks during which they were regularly subjected to the
      electroencephalographic recording of SWDs. The KD did not influence the number
      and duration of SWDs despite a 15-22% decrease in plasma glucose levels and a
      large increase in beta-hydroxybutyrate levels. Likewise, the KD did not affect
      the level of expression of the blood-brain barrier glucose transporter GLUT1 or
      of the monocarboxylate transporters, MCT1 and MCT2. This report extends the
      observation in humans that the KD does not appear to show effectiveness in
      intractable atypical absence epilepsy to this model of typical childhood absence
      epilepsy which responds to specific antiepileptic drugs.

PMID- 19393030
TI  - Mild reduction in the activity of the alpha-ketoglutarate dehydrogenase complex
      elevates GABA shunt and glycolysis.
AB  - Diminished energy metabolism and reduced activity of brain alpha-ketoglutarate
      dehydrogenase complex (KGDHC) occur in a number of neurodegenerative diseases.
      The relation between diminished KGDHC activity and altered energy metabolism is
      unknown. The present study tested whether a reduction in the KGDHC activity would
      alter cellular metabolism by comparing metabolism of [U-13C]glucose in a human
      embryonic kidney cell line (E2k100) to one in which the KGDHC activity was about
      70% of control (E2k67). After a 2 h incubation of the cells with [U-13C]glucose,
      the E2k67 cells showed a greater increase in 13C labeling of alanine compared
      with the E2k100 cells. This suggested an increase in glycolysis. Furthermore, an
      increase in labeled lactate after 12 h incubation supported the suggestion of an
      increased glycolysis in the E2k67 cells. Increased GABA shunt in the E2k67 cells
      was indicated by increased 13C labeling of GABA at both 2 and 12 h compared with
      the control cells. GABA concentration as determined by HPLC was also increased in
      the E2k67 cells compared with the control cells. However, the GABA shunt was not
      sufficient to normalize metabolism in the E2k67 cells compared with control at 2
      or 12 h. However, by 24 h metabolism had normalized (i.e. labeling was similar in
      E2k67 and E2k100). Thus, the data are consistent with an enhanced glycolysis and
      GABA shunt in response to a mild reduction in KGDHC. Our findings indicate that a
      mild change in KGDHC activity can lead to large changes in metabolism. The
      changes may maintain normal energy metabolism but make the cells more vulnerable
      to perturbations such as occur with oxidants.

PMID- 19393031
TI  - Inhibition of the alpha-ketoglutarate dehydrogenase-mediated reactive oxygen
      species generation by lipoic acid.
AB  - Dihydrolipoamide dehydrogenase (LADH) is a flavo-enzyme that serves as a subunit
      of alpha-ketoglutarate dehydrogenase complex (alpha-KGDHC). Reactive oxygen
      species (ROS) generation by alpha-KGDHC has been assigned to LADH (E3 subunit)
      and explained by the diaphorase activity of E3. Dysfunctions of alpha-KGDHC and
      concurrent ROS production have been implicated in neurodegeneration, ischemia
      reperfusion, and other pathological conditions. In this work we investigated the
      in-depth details of ROS generation by isolated LADH and alpha-KGDHC. We found a
      parallel generation of superoxide and hydrogen peroxide by the E3 subunit of
      alpha-KGDHC which could be blocked by lipoic acid (LA) acting on a site upstream
      of the E3 subunit. The pathologically relevant ROS generation (at high NADH/NAD+
      ratio and low pH) in the reverse mode of alpha-KGDHC could also be inhibited by
      LA. Our results contradict the previously proposed mechanism for pH-dependent ROS
      generation by LADH, showing no disassembling of the E3 functional homodimer at
      acidic pH using a physiologically relevant method for the examination. It is also
      suggested that LA could be beneficial in reducing the cell damage related to
      excessive ROS generation under pathological conditions.

PMID- 19393032
TI  - Rescue of Abeta(1-42)-induced memory impairment in day-old chick by facilitation
      of astrocytic oxidative metabolism: implications for Alzheimer's disease.
AB  - Administration of small oligomeric beta-amyloid (Abeta)(1-42) 45 min before one
      trial bead discrimination learning in day-old chicks abolishes consolidation of
      learning 30 min post-training (Gibbs et al. Neurobiol. Aging, in press).
      Administration of the beta3-adrenergic agonist CL316243, which specifically
      stimulates astrocytic but not neuronal glucose uptake, rescues Abeta impaired
      memory. Weakly reinforced training can be consolidated by various metabolic
      substrates and we have demonstrated neuronal dependence on oxidative metabolism
      of glucose soon after training versus astrocytic glucose dependence 20 min later.
      Based on these findings we examined whether different metabolic substrates were
      able to counteract memory inhibition by Abeta(1-42). Although lactate, the medium
      chain fatty acid octanoate, and the ketone body beta-hydroxybutyrate consolidated
      weakly reinforced training when injected close to learning, none of them were
      able to salvage Abeta-impaired memory; at this early time. All three metabolites
      and the astrocytic-specific acetate consolidated weak learning and rescued Abeta
      impaired memory when injected 10-20 min post-training. However, neither glucose
      nor insulin rescued memory when injected at 20 min. Rescue of memory by providing
      astrocytes with alternative substrates for oxidative metabolism suggests that
      Abeta(1-42) exerts its amnestic effects specifically by impairing astrocytic
      glycolysis.

PMID- 19393033
TI  - Redox dependence and compartmentation of [13C]pyruvate in the brain of deuterated
      rats bearing implanted C6 gliomas.
AB  - We investigated the redox dependence and compartmentation of the pyruvate pool in
      the brain of partially deuterated rats bearing C6 gliomas. Adult male Wistar rats
      implanted with C6 cells drunk 2H2O (50% v/v) or tap water for 9 days before they
      were infused with solutions containing [1-13C]glucose and [2-13C]pyruvate or [U
      13C3]lactate. Their brains were fixed with high-power focused microwaves and
      biopsies prepared from the contralateral, ipsilateral, and tumor regions. 13C NMR
      analysis of the extracts allowed the determination of the relative amounts of
      [13C]lactate isotopomers derived from infused glucose or monocarboxylates. The
      relative amounts of [3-13C]lactate derived from glucose to the [2-13C] or [U
      13C3]lactate isotopomers derived from monocarboxylates decreased in the order
      contralateral > ipsilateral > tumor regions, revealing a progressive reduction in
      glycolysis for regions containing increasing endogenous lactate concentrations.
      Cortical astrocytes depicted similar reductions in glycolysis when incubated with
      [1,2-13C2]glucose and increasing concentrations of [3-13C]lactate. Deuterated
      animals bearing C6 tumors, infused with [1-13C]glucose and [2-13C]pyruvate,
      showed different deuterium enrichments in the methyl groups of cerebral [3-13C]
      and [2-13C]lactate, revealing a slow mixing of the [3-13C] and [2-13C]pyruvate
      precursors in the 2H exchange timescale of their methyl groups. Together, these
      evidences reveal the role of the redox state of the pyruvate pool derived from
      monocarboxylates in the modulation of cerebral glycolytic flux in vivo and in
      vitro.

PMID- 19393034
TI  - Protein kinase G is involved in ammonia-induced swelling of astrocytes.
AB  - Ammonia-induced swelling of astrocytes is a primary cause of brain edema
      associated with acute hepatic encephalopathy. Previous studies have shown that
      ammonia transiently increases cGMP in brain in vivo and in cultured astrocytes in
      vitro. We hypothesized that protein kinase G (PKG), an enzyme activated by cGMP
      and implicated in regulation of cell shape, size, and/or volume in peripheral and
      CNS cells, may play a role in the ammonia-induced astrocytic volume increase.
      Treatment of cultured rat cortical astrocytes with 1 or 5 mM NH4Cl (ammonia) for
      24 h increased their cell volume by 50% and 80% above control, respectively, as
      measured by confocal imaging followed by 3D computational analysis. A cGMP
      analog, 8-(4-chlorophenylthio)-cGMP, increased the cell volume in control cells
      and potentiated the increase in 1 mM ammonia-treated cells. A soluble guanylate
      cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) abrogated, and a
      PKG inhibitor [8-(4-chlorophenylthio)-cGMP-thioate, Rp-isomer] dose-dependently
      reduced the cell volume-increasing effect of 5 mM ammonia. The results suggest
      that (i) PKG may play a permissive role in ammonia-induced astrocytic swelling
      and (ii) elevation of brain cGMP associated with acute exposure to ammonia in
      vivo may aggravate the ensuing brain edema.

PMID- 19393035
TI  - Calcium in the mechanism of ammonia-induced astrocyte swelling.
AB  - Brain edema, due largely to astrocyte swelling, is an important clinical problem
      in patients with acute liver failure. While mechanisms underlying astrocyte
      swelling in this condition are not fully understood, ammonia and associated
      oxidative/nitrosative stress appear to be involved. Mechanisms responsible for
      the increase in reactive oxygen/nitrogen species (RONS) and their role in ammonia
      induced astrocyte swelling, however, are poorly understood. Recent studies have
      demonstrated a transient increase in intracellular Ca2+ in cultured astrocytes
      exposed to ammonia. As Ca2+ is a known inducer of RONS, we investigated potential
      mechanisms by which Ca2+ may be responsible for the production of RONS and cell
      swelling in cultured astrocytes after treatment with ammonia. Exposure of
      cultured astrocytes to ammonia (5 mM) increased the formation of free radicals,
      including nitric oxide, and such increase was significantly diminished by
      treatment with the Ca2+ chelator 1,2-bis-(o-aminophenoxy)-ethane-N,N,-N',N'
      tetraacetic acid tetraacetoxy-methyl ester (BAPTA). We then examined the activity
      of Ca2+-dependent enzymes that are known to generate RONS and found that ammonia
      significantly increased the activities of NADPH oxidase (NOX), constitutive
      nitric oxide synthase (cNOS), and phospholipase A2 (PLA2) and such increases in
      activity were significantly diminished by BAPTA. Pre-treatment of cultures with 7
      nitroindazole, apocyanin, and quinacrine, respective inhibitors of cNOS, NOX, and
      PLA2, all significantly diminished RONS production. Additionally, treatment of
      cultures with BAPTA or with inhibitors of cNOS, NOX, and PLA2 reduced ammonia
      induced astrocyte swelling. These studies suggest that the ammonia-induced rise
      in intracellular Ca2+ activates free radical producing enzymes that ultimately
      contribute to the mechanism of astrocyte swelling.

PMID- 19393036
TI  - Altered fatty acid metabolism and composition in cultured astrocytes under
      hyperammonemic conditions.
AB  - In vitro 1H- and 13C-NMR spectroscopy was used to investigate the effect of
      ammonia on fatty acid synthesis and composition in cultured astrocytes. Cells
      were incubated 3 and 24 h with 5 mM ammonia in the presence or absence of the
      glutamine synthetase inhibitor methionine sulfoximine. An increase of de novo
      synthesized fatty acids and the glycerol subunit of lipids was observed after 3 h
      treatment with ammonia (35% and 40% over control, respectively), the initial time
      point examined. Both parameters further increased significantly to 85% and 60%
      over control after 24 h ammonia treatment. Three hours incubation with ammonia
      increased the synthesis of diacylglycerides, while formation of triacylglycerides
      was decreased (40% over and 15% under control, respectively). The degradation of
      fatty acids was not affected by ammonia treatment. Furthermore, ammonia caused
      alterations in the composition of fatty acids, e.g. increased mono- and decreased
      polyunsaturated fatty acids (85% over and 15% under control concentrations,
      respectively). The decrease of polyunsaturated fatty acids was even more
      pronounced in isolated astrocytic mitochondria (39% lower than controls). Our
      results suggest ammonia-induced abnormalities in astrocytic membranes, which may
      be related to astrocytic mitochondrial dysfunction in hyperammonemic states. Most
      of the observed effects of ammonia on fatty acid synthesis and composition were
      ameliorated when glutamine synthetase was inhibited by methionine sulfoximine,
      supporting a pathological role of glutamine in ammonia toxicity. This study
      further emphasizes the importance of investigating the relative contribution of
      exogenous ammonia, effects of glutamine and of glutamine-derived ammonia on
      astrocytes and astrocytic mitochondria.

PMID- 19393038
TI  - A whole-genome assembly of the domestic cow, Bos taurus.
AB  - BACKGROUND: The genome of the domestic cow, Bos taurus, was sequenced using a
      mixture of hierarchical and whole-genome shotgun sequencing methods. RESULTS: We
      have assembled the 35 million sequence reads and applied a variety of assembly
      improvement techniques, creating an assembly of 2.86 billion base pairs that has
      multiple improvements over previous assemblies: it is more complete, covering
      more of the genome; thousands of gaps have been closed; many erroneous
      inversions, deletions, and translocations have been corrected; and thousands of
      single-nucleotide errors have been corrected. Our evaluation using independent
      metrics demonstrates that the resulting assembly is substantially more accurate
      and complete than alternative versions. CONCLUSIONS: By using independent mapping
      data and conserved synteny between the cow and human genomes, we were able to
      construct an assembly with excellent large-scale contiguity in which a large
      majority (approximately 91%) of the genome has been placed onto the 30 B. taurus
      chromosomes. We constructed a new cow-human synteny map that expands upon
      previous maps. We also identified for the first time a portion of the B. taurus Y
      chromosome.

PMID- 19393039
TI  - Nicotine-induced brain metabolism associated with anger provocation.
AB  - Cortico-limbic brain activity associated with anger may be susceptible to
      nicotine and, thus, may contribute to smoking initiation and nicotine addiction.
      The purpose of the study was to identify the brain regions that are most reactive
      to nicotine and show the greatest association with anger task performance. Twenty
      adult nonsmokers (9 women, 11 men) participated in two laboratory sessions to
      assess brain metabolism with fluoro deoxy-glucose Positron Emission Topography
      (FDG-PET) in response to nicotine and placebo patches during an anger provocation
      task. Outcome variables for the anger provocation task were reaction time,
      intensity and length of retaliation. Reaction time was associated with nicotine
      induced changes in the left thalamus. Length of retaliation was associated with a
      functionally linked set of cortical and subcortical structures such as right
      frontal lobe, right anterior cingulate (BA 24), right uncus, left parietal lobe,
      left BA 11, left cingulate, left BA 25, left amygdala, left BA 30, left BA 38 and
      BA 9. These findings reveal the underlying brain circuitry targeted by nicotine
      during anger provocation.

PMID- 19393040
TI  - The bovine lactation genome: insights into the evolution of mammalian milk.
AB  - BACKGROUND: The newly assembled Bos taurus genome sequence enables the linkage of
      bovine milk and lactation data with other mammalian genomes. RESULTS: Using
      publicly available milk proteome data and mammary expressed sequence tags, 197
      milk protein genes and over 6,000 mammary genes were identified in the bovine
      genome. Intersection of these genes with 238 milk production quantitative trait
      loci curated from the literature decreased the search space for milk trait
      effectors by more than an order of magnitude. Genome location analysis revealed a
      tendency for milk protein genes to be clustered with other mammary genes. Using
      the genomes of a monotreme (platypus), a marsupial (opossum), and five placental
      mammals (bovine, human, dog, mice, rat), gene loss and duplication, phylogeny,
      sequence conservation, and evolution were examined. Compared with other genes in
      the bovine genome, milk and mammary genes are: more likely to be present in all
      mammals; more likely to be duplicated in therians; more highly conserved across
      Mammalia; and evolving more slowly along the bovine lineage. The most divergent
      proteins in milk were associated with nutritional and immunological components of
      milk, whereas highly conserved proteins were associated with secretory processes.
      CONCLUSIONS: Although both copy number and sequence variation contribute to the
      diversity of milk protein composition across species, our results suggest that
      this diversity is primarily due to other mechanisms. Our findings support the
      essentiality of milk to the survival of mammalian neonates and the establishment
      of milk secretory mechanisms more than 160 million years ago.

PMID- 19393041
TI  - Non-expanded adipose stromal vascular fraction cell therapy for multiple
      sclerosis.
AB  - The stromal vascular fraction (SVF) of adipose tissue is known to contain
      mesenchymal stem cells (MSC), T regulatory cells, endothelial precursor cells,
      preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous
      adipose tissue implantation is supported by extensive use of this procedure in
      cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose
      derived MSC. Equine and canine studies demonstrating anti-inflammatory and
      regenerative effects of non-expanded SVF cells have yielded promising results.
      Although non-expanded SVF cells have been used successfully in accelerating
      healing of Crohn's fistulas, to our knowledge clinical use of these cells for
      systemic immune modulation has not been reported. In this communication we
      discuss the rationale for use of autologous SVF in treatment of multiple
      sclerosis and describe our experiences with three patients. Based on this
      rationale and initial experiences, we propose controlled trials of autologous SVF
      in various inflammatory conditions.

PMID- 19393042
TI  - Two-stage genome-wide association study identifies integrin beta 5 as having
      potential role in bull fertility.
AB  - BACKGROUND: Fertility is one of the most critical factors controlling biological
      and financial performance of animal production systems and genetic improvement of
      lines. The objective of this study was to identify molecular defects in the sperm
      that are responsible for uncompensable fertility in Holstein bulls. We performed
      a comprehensive genome wide analysis of single nucleotide polymorphisms (SNP) for
      bull fertility followed by a second-stage replication in additional bulls for a
      restricted set of markers. RESULTS: In the Phase I association study, we
      genotyped the genomic sperm DNA of 10 low-fertility and 10 high-fertility bulls
      using Bovine SNP Gene Chips containing approximately 10,000 random SNP markers.
      In these animals, 8,207 markers were found to be polymorphic, 97 of which were
      significantly associated with fertility (p < 0.01). In the Phase II study, we
      tested the four most significant SNP from the Phase I study in 101 low-fertility
      and 100 high-fertility bulls, with two SNPs (rs29024867 and rs41257187)
      significantly replicated. Rs29024867 corresponds to a nucleotide change of C -->
      G 2,190 bp 3' of the collagen type I alpha 2 gene on chromosome 4, while the
      rs41257187 (C --> T) is in the coding region of integrin beta 5 gene on
      chromosome 1. The SNP rs41257187 induces a synonymous (Proline --> Proline),
      suggesting disequilibrium with the true causative locus (i), but we found that
      the incubation of bull spermatozoa with integrin beta 5 antibodies significantly
      decreased the ability to fertilize oocytes. Our findings suggest that the bovine
      sperm integrin beta 5 protein plays a role during fertilization and could serve
      as a positional or functional marker of bull fertility. CONCLUSION: We have
      identified molecular markers associated with bull fertility and established that
      at least one of the genes harboring such variation has a role in fertility. The
      findings are important in understanding mechanisms of uncompensatory infertility
      in bulls, and in other male mammals. The findings set the stage for more
      hypothesis-driven research aimed at discovering the role of variation in the
      genome that affect fertility and that can be used to identify molecular
      mechanisms of development.

PMID- 19393043
TI  - A high density linkage map of the bovine genome.
AB  - BACKGROUND: Recent technological advances have made it possible to efficiently
      genotype large numbers of single nucleotide polymorphisms (SNPs) in livestock
      species, allowing the production of high-density linkage maps. Such maps can be
      used for quality control of other SNPs and for fine mapping of quantitative trait
      loci (QTL) via linkage disequilibrium (LD). RESULTS: A high-density bovine
      linkage map was constructed using three types of markers. The genotypic
      information was obtained from 294 microsatellites, three milk protein haplotypes
      and 6769 SNPs. The map was constructed by combining genetic (linkage) and
      physical information in an iterative mapping process. Markers were mapped to
      3,155 unique positions; the 6,924 autosomal markers were mapped to 3,078 unique
      positions and the 123 non-pseudoautosomal and 19 pseudoautosomal sex chromosome
      markers were mapped to 62 and 15 unique positions, respectively. The linkage map
      had a total length of 3,249 cM. For the autosomes the average genetic distance
      between adjacent markers was 0.449 cM, the genetic distance between unique map
      positions was 1.01 cM and the average genetic distance (cM) per Mb was 1.25.
      CONCLUSION: There is a high concordance between the order of the SNPs in our
      linkage map and their physical positions on the most recent bovine genome
      sequence assembly (Btau 4.0). The linkage maps provide support for fine mapping
      projects and LD studies in bovine populations. Additionally, the linkage map may
      help to resolve positions of unassigned portions of the bovine genome.

PMID- 19393044
TI  - SNP HiTLink: a high-throughput linkage analysis system employing dense SNP data.
AB  - BACKGROUND: During this recent decade, microarray-based single nucleotide
      polymorphism (SNP) data are becoming more widely used as markers for linkage
      analysis in the identification of loci for disease-associated genes. Although
      microarray-based SNP analyses have markedly reduced genotyping time and cost
      compared with microsatellite-based analyses, applying these enormous data to
      linkage analysis programs is a time-consuming step, thus, necessitating a high
      throughput platform. RESULTS: We have developed SNP HiTLink (SNP High Throughput
      Linkage analysis system). In this system, SNP chip data of the Affymetrix Mapping
      100 k/500 k array set and Genome-Wide Human SNP array 5.0/6.0 can be directly
      imported and passed to parametric or model-free linkage analysis programs; MLINK,
      Superlink, Merlin and Allegro. Various marker-selecting functions are implemented
      to avoid the effect of typing-error data, markers in linkage equilibrium or to
      select informative data. CONCLUSION: The results using the 100 k SNP dataset were
      comparable or even superior to those obtained from analyses using microsatellite
      markers in terms of LOD scores obtained. General personal computers are
      sufficient to execute the process, as runtime for whole-genome analysis was less
      than a few hours. This system can be widely applied to linkage analysis using
      microarray-based SNP data and with which one can expect high-throughput and
      reliable linkage analysis.

PMID- 19393045
TI  - Phylogenetic reconstruction and the identification of ancient polymorphism in the
      Bovini tribe (Bovidae, Bovinae).
AB  - BACKGROUND: The Bovinae subfamily incorporates an array of antelope, buffalo and
      cattle species. All of the members of this subfamily have diverged recently. Not
      surprisingly, a number of phylogenetic studies from molecular and morphological
      data have resulted in ambiguous trees and relationships amongst species,
      especially for Yak and Bison species. A partial phylogenetic reconstruction of 13
      extant members of the Bovini tribe (Bovidae, Bovinae) from 15 complete or
      partially sequenced autosomal genes is presented. RESULTS: We identified 3
      distinct lineages after the Bovini split from the Boselaphini and Tragelaphini
      tribes, which has lead to the (1) Buffalo clade (Bubalus and Syncerus species)
      and a more recent divergence leading to the (2) Banteng, Gaur and Mithan and (3)
      Domestic cattle clades. A fourth lineage may also exist that leads to Bison and
      Yak. However, there was some ambiguity as to whether this was a divergence from
      the Banteng/Gaur/Mithan or the Domestic cattle clade. From an analysis of
      approximately 30,000 sites that were amplified in all species 133 sites were
      identified with ambiguous inheritance, in that all trees implied more than one
      mutation at the same site. Closer examination of these sites has identified that
      they are the result of ancient polymorphisms that have subsequently undergone
      lineage sorting in the Bovini tribe, of which 53 have remained polymorphic since
      Bos and Bison species last shared a common ancestor with Bubalus between 5-8
      million years ago (MYA). CONCLUSION: Uncertainty arises in our phylogenetic
      reconstructions because many species in the Bovini diverged over a short period
      of time. It appears that a number of sites with ambiguous inheritance have been
      maintained in subsequent populations by chance (lineage sorting) and that they
      have contributed to an association between Yak and Domestic cattle and an
      unreliable phylogenetic reconstruction for the Bison/Yak clade. Interestingly, a
      number of these aberrant sites are in coding sections of the genome and their
      identification may have important implications for studying the neutral rate of
      mutation at nonsynonymous sites. The presence of these sites could help account
      for the apparent contradiction between levels of polymorphism and effective
      population size in domesticated cattle.

PMID- 19393046
TI  - Evaluation of the effect of patient education on rates of falls in older hospital
      patients: description of a randomised controlled trial.
AB  - BACKGROUND: Accidental falls by older patients in hospital are one of the most
      commonly reported adverse events. Falls after discharge are also common. These
      falls have enormous physical, psychological and social consequences for older
      patients, including serious physical injury and reduced quality of life, and are
      also a source of substantial cost to health systems worldwide. There have been a
      limited number of randomised controlled trials, mainly using multifactorial
      interventions, aiming to prevent older people falling whilst inpatients. Trials
      to date have produced conflicting results and recent meta-analyses highlight that
      there is still insufficient evidence to clearly identify which interventions may
      reduce the rate of falls, and falls related injuries, in this population. METHODS
      AND DESIGN: A prospective randomised controlled trial (n = 1206) is being
      conducted at two hospitals in Australia. Patients are eligible to be included in
      the trial if they are over 60 years of age and they, or their family or guardian,
      give written consent. Participants are randomised into three groups. The control
      group continues to receive usual care. Both intervention groups receive a
      specifically designed patient education intervention on minimising falls in
      addition to usual care. The education is delivered by Digital Video Disc (DVD)
      and written workbook and aims to promote falls prevention activities by
      participants. One of the intervention groups also receives follow up education
      training visits by a health professional. Blinded assessors conduct baseline and
      discharge assessments and follow up participants for 6 months after discharge.
      The primary outcome measure is falls by participants in hospital. Secondary
      outcome measures include falls at home after discharge, knowledge of falls
      prevention strategies and motivation to engage in falls prevention activities
      after discharge. All analyses will be based on intention to treat principle.
      DISCUSSION: This trial will examine the effect of a single intervention
      (specifically designed patient education) on rates of falls in older patients in
      hospital and after discharge. The results will provide robust recommendations for
      clinicians and researchers about the role of patient education in this
      population. The study has the potential to identify a new intervention that may
      reduce rates of falls in older hospital patients and could be readily duplicated
      and applied in a wide range of clinical settings.

PMID- 19393047
TI  - Genome wide signatures of positive selection: the comparison of independent
      samples and the identification of regions associated to traits.
AB  - BACKGROUND: The goal of genome wide analyses of polymorphisms is to achieve a
      better understanding of the link between genotype and phenotype. Part of that
      goal is to understand the selective forces that have operated on a population.
      RESULTS: In this study we compared the signals of selection, identified through
      population divergence in the Bovine HapMap project, to those found in an
      independent sample of cattle from Australia. Evidence for population
      differentiation across the genome, as measured by FST, was highly correlated in
      the two data sets. Nevertheless, 40% of the variance in FST between the two
      studies was attributed to the differences in breed composition. Seventy six
      percent of the variance in FST was attributed to differences in SNP composition
      and density when the same breeds were compared. The difference between FST of
      adjacent loci increased rapidly with the increase in distance between SNP,
      reaching an asymptote after 20 kb. Using 129 SNP that have highly divergent FST
      values in both data sets, we identified 12 regions that had additive effects on
      the traits residual feed intake, beef yield or intramuscular fatness measured in
      the Australian sample. Four of these regions had effects on more than one trait.
      One of these regions includes the R3HDM1 gene, which is under selection in
      European humans. CONCLUSION: Firstly, many different populations will be
      necessary for a full description of selective signatures across the genome, not
      just a small set of highly divergent populations. Secondly, it is necessary to
      use the same SNP when comparing the signatures of selection from one study to
      another. Thirdly, useful signatures of selection can be obtained where many of
      the groups have only minor genetic differences and may not be clearly separated
      in a principal component analysis. Fourthly, combining analyses of genome wide
      selection signatures and genome wide associations to traits helps to define the
      trait under selection or the population group in which the QTL is likely to be
      segregating. Finally, the FST difference between adjacent loci suggests that
      150,000 evenly spaced SNP will be required to study selective signatures in all
      parts of the bovine genome.

PMID- 19393048
TI  - Molecular evolution of the Bovini tribe (Bovidae, Bovinae): is there evidence of
      rapid evolution or reduced selective constraint in Domestic cattle?
AB  - BACKGROUND: If mutation within the coding region of the genome is largely not
      adaptive, the ratio of nonsynonymous (dN) to synonymous substitutions (dS) per
      site (dN/dS) should be approximately equal among closely related species.
      Furthermore, dN/dS in divergence between species should be equivalent to dN/dS in
      polymorphisms. This hypothesis is of particular interest in closely related
      members of the Bovini tribe, because domestication has promoted rapid phenotypic
      divergence through strong artificial selection of some species while others
      remain undomesticated. We examined a number of genes that may be involved in milk
      production in Domestic cattle and a number of their wild relatives for evidence
      that domestication had affected molecular evolution. Elevated rates of dN/dS were
      further queried to determine if they were the result of positive selection, low
      effective population size (N(e)) or reduced selective constraint. RESULTS: We
      have found that the domestication process has contributed to higher dN/dS ratios
      in cattle, especially in the lineages leading to the Domestic cow (Bos taurus)
      and Mithan (Bos frontalis) and within some breeds of Domestic cow. However, the
      high rates of dN/dS polymorphism within B. taurus when compared to species
      divergence suggest that positive selection has not elevated evolutionary rates in
      these genes. Likewise, the low rate of dN/dS in Bison, which has undergone a
      recent population bottleneck, indicates a reduction in population size alone is
      not responsible for these observations. CONCLUSION: The effect of selection
      depends on effective population size and the selection coefficient (N(e)s).
      Typically under domestication both selection pressure for traits important in
      fitness in the wild and Ne are reduced. Therefore, reduced selective constraint
      could be responsible for the observed elevated evolutionary ratios in
      domesticated species, especially in B. taurus and B. frontalis, which have the
      highest dN/dS in the Bovini. This may have important implications for tests of
      selection such as the McDonald-Kreitman test. Surprisingly we have also detected
      a significant difference in the supposed neutral substitution rate between
      synonymous and noncoding sites in the Bovine genome, with a 30% higher rate of
      substitution at synonymous sites. This is due, at least in part, to an excess of
      the highly mutable CpG dinucleotides at synonymous sites, which will have
      implications for time of divergence estimates from molecular data.

PMID- 19393049
TI  - Small local variations in B-form DNA lead to a large variety of global geometries
      which can accommodate most DNA-binding protein motifs.
AB  - BACKGROUND: An important question of biological relevance is the polymorphism of
      the double-helical DNA structure in its free form, and the changes that it
      undergoes upon protein-binding. We have analysed a database of free DNA crystal
      structures to assess the inherent variability of the free DNA structure and have
      compared it with a database of protein-bound DNA crystal structures to ascertain
      the protein-induced variations. RESULTS: Most of the dinucleotide steps in free
      DNA display high flexibility, assuming different conformations in a sequence
      dependent fashion. With the exception of the AA/TT and GA/TC steps, which are 'A
      phobic', and the GG/CC step, which is 'A-philic', the dinucleotide steps show no
      preference for A or B forms of DNA. Protein-bound DNA adopts the B-conformation
      most often. However, in certain cases, protein-binding causes the DNA backbone to
      take up energetically unfavourable conformations. At the gross structural level,
      several protein-bound DNA duplexes are observed to assume a curved conformation
      in the absence of any large distortions, indicating that a series of normal
      structural parameters at the dinucleotide and trinucleotide level, similar to the
      ones in free B-DNA, can give rise to curvature at the overall level. CONCLUSION:
      The results illustrate that the free DNA molecule, even in the crystalline state,
      samples a large amount of conformational space, encompassing both the A and the B
      forms, in the absence of any large ligands. A-form as well as some non-A, non-B,
      distorted geometries are observed for a small number of dinucleotide steps in DNA
      structures bound to the proteins belonging to a few specific families. However,
      for most of the bound DNA structures, across a wide variety of protein families,
      the average step parameters for various dinucleotide sequences as well as
      backbone torsion angles are observed to be quite close to the free 'B-like' DNA
      oligomer values, highlighting the flexibility and biological significance of this
      structural form.

PMID- 19393050
TI  - Bos taurus genome assembly.
AB  - BACKGROUND: We present here the assembly of the bovine genome. The assembly
      method combines the BAC plus WGS local assembly used for the rat and sea urchin
      with the whole genome shotgun (WGS) only assembly used for many other animal
      genomes including the rhesus macaque. RESULTS: The assembly process consisted of
      multiple phases: First, BACs were assembled with BAC generated sequence, then
      subsequently in combination with the individual overlapping WGS reads. Different
      assembly parameters were tested to separately optimize the performance for each
      BAC assembly of the BAC and WGS reads. In parallel, a second assembly was
      produced using only the WGS sequences and a global whole genome assembly method.
      The two assemblies were combined to create a more complete genome representation
      that retained the high quality BAC-based local assembly information, but with
      gaps between BACs filled in with the WGS-only assembly. Finally, the entire
      assembly was placed on chromosomes using the available map information.Over 90%
      of the assembly is now placed on chromosomes. The estimated genome size is 2.87
      Gb which represents a high degree of completeness, with 95% of the available EST
      sequences found in assembled contigs. The quality of the assembly was evaluated
      by comparison to 73 finished BACs, where the draft assembly covers between 92.5
      and 100% (average 98.5%) of the finished BACs. The assembly contigs and scaffolds
      align linearly to the finished BACs, suggesting that misassemblies are rare.
      Genotyping and genetic mapping of 17,482 SNPs revealed that more than 99.2% were
      correctly positioned within the Btau_4.0 assembly, confirming the accuracy of the
      assembly. CONCLUSION: The biological analysis of this bovine genome assembly is
      being published, and the sequence data is available to support future bovine
      research.

PMID- 19393051
TI  - Quality of life and the impact of drug toxicities in a South African community
      based antiretroviral programme.
AB  - BACKGROUND: The impact of highly active antiretroviral therapy (HAART) on health
      related quality of life has been widely researched in the developed world, but
      there are few data from sub-Saharan Africa, where the vast majority of HIV
      infected individuals live. This study examined health-related quality of life
      among HIV-positive individuals initiating HAART in Cape Town, South Africa, and
      explored the impact of HAART-related drug toxicities on quality of life. METHODS:
      Health-related quality of life was assessed using a standardised questionnaire,
      the Medical Outcomes Survey Short Form 36. Physical health summary scores and
      mental health summary scores were compared pre-HAART and at regular intervals
      during the first 48 weeks of HAART. The relationships between socio-demographic,
      baseline and on-treatment variables and decline in health-related quality of
      life, as well as the impact of drug toxicities on quality of life, were assessed
      in unadjusted bivariate and adjusted multivariate analyses. RESULTS: Two hundred
      and ninety-five patients were enrolled into the study. There was a significant
      increase in health-related quality of life during the first 48 weeks on HAART.
      The median physical health summary score increased from 45 to 53 units (p <
      0.001) and median mental health summary score increased from 45 to 50 units (p <
      0.001).The bulk of this increase occurred during the first 16 weeks. Overall, 23%
      of participants experienced a decline in their physical health summary score,
      while 34% showed a decline in the mental health summary score. Average drops in
      median physical and mental health summary scores were 8.4 units (SD 9.31) and 9.9
      (SD 11.4) units respectively. Participants with drug toxicity had lower physical
      health summary scores than participants without drug toxicity at all time points.
      However, only three participants with toxicity (27%) reported an actual decline
      in health-related quality of life by week 48. Drug toxicities had little impact
      on mental health summary scores. CONCLUSION: These results confirm the health
      related quality of life benefits of HAART. While the majority of patients
      experienced a significant improvement in health-related quality of life on HAART,
      up to a third of patients reported declines in this quality of life. This was
      largely related to better baseline clinical state. HAART-related drug toxicities
      did not have a significant impact on health-related quality of life during the
      first year of HAART, which supports the ongoing use of the current national first
      line regimen.

PMID- 19393052
TI  - Relapse prevention in UK Stop Smoking Services: a qualitative study of health
      professionals' views and beliefs.
AB  - BACKGROUND: NHS Stop Smoking Services in the UK provide cost effective smoking
      cessation interventions, but approximately 75% of smokers who are abstinent at 4
      weeks relapse to smoking by 12 months. This study aimed to explore health
      professionals' understanding of relapse prevention interventions (RPIs), the
      feasibility of offering such support and whether and how these are currently used
      in UK NHS Stop Smoking Services. METHODS: Sixteen health professionals working in
      UK NHS Stop Smoking Services, selected from those attending a national conference
      were interviewed and Framework Analysis was used to identify recurrent key themes
      and concepts in their perceptions and experiences of providing relapse prevention
      interventions (RPIs). RESULTS: Interviewees had diverse perceptions of relapse
      prevention as a concept. Whilst relapse prevention was largely seen as support to
      prevent abstinent smokers from relapsing to smoking, some interviewees stated
      that RPIs were being delivered to lapsed or relapsed smokers. Current provision
      of RPIs was most commonly described as behavioural counselling being offered
      predominantly after completed cessation treatment, often in the format of
      'rolling groups' which the client was encouraged to attend. Commonly identified
      barriers to the introduction of RPIs were funding and government targets focussed
      on short term cessation, smokers' low uptake of offered RPIs and an uncertain
      evidence base for their effectiveness. Interviewees were positive about the
      potential use of pharmacotherapy for relapse prevention, but were negative about
      the possibility of introducing proactive telephone counselling for this purpose.
      CONCLUSION: There is currently no shared understanding of the concept of relapse
      prevention amongst this sample of health professionals working in UK NHS Stop
      Smoking Services. For RPIs to be systematically delivered via these services, a
      commonly-held, widely-accepted and understood definition of relapse prevention
      would be needed. Other barriers towards introducing RPIs, such as their weak
      evidence and the short term cessation-focussed targets against which UK stop
      smoking services are measured, would also need addressing and interventions which
      are acceptable to abstinent smokers would need to be developed.

PMID- 19393053
TI  - An examination of positive selection and changing effective population size in
      Angus and Holstein cattle populations (Bos taurus) using a high density SNP
      genotyping platform and the contribution of ancient polymorphism to genomic
      diversity in Domestic cattle.
AB  - BACKGROUND: Identifying recent positive selection signatures in domesticated
      animals could provide information on genome response to strong directional
      selection from domestication and artificial selection. With the completion of the
      cattle genome, private companies are now providing large numbers of polymorphic
      markers for probing variation in domestic cattle (Bos taurus). We analysed over
      7,500 polymorphic single nucleotide polymorphisms (SNP) in beef (Angus) and dairy
      (Holstein) cattle and outgroup species Bison, Yak and Banteng in an indirect test
      of inbreeding and positive selection in Domestic cattle. RESULTS: Outgroup
      species: Bison, Yak and Banteng, were genotyped with high levels of success (90%)
      and used to determine ancestral and derived allele states in domestic cattle.
      Frequency spectrums of the derived alleles in Angus and Holstein were examined
      using Fay and Wu's H test. Significant divergences from the predicted frequency
      spectrums expected under neutrality were identified. This appeared to be the
      result of combined influences of positive selection, inbreeding and ascertainment
      bias for moderately frequent SNP. Approximately 10% of all polymorphisms
      identified as segregating in B. taurus were also segregating in Bison, Yak or
      Banteng; highlighting a large number of polymorphisms that are ancient in origin.
      CONCLUSION: These results suggest that a large effective population size (N(e))
      of approximately 90,000 or more existed in B. taurus since they shared a common
      ancestor with Bison, Yak and Banteng ~1-2 million years ago (MYA). More recently
      N(e) decreased sharply probably associated with domestication. This may partially
      explain the paradox of high levels of polymorphism in Domestic cattle and the
      relatively small recent N(e) in this species. The period of inbreeding caused Fay
      and Wu's H statistic to depart from its expectation under neutrality mimicking
      the effect of selection. However, there was also evidence for selection, because
      high frequency derived alleles tended to cluster near each other on the genome.

PMID- 19393054
TI  - High-resolution haplotype block structure in the cattle genome.
AB  - BACKGROUND: The Bovine HapMap Consortium has generated assay panels to genotype
      ~30,000 single nucleotide polymorphisms (SNPs) from 501 animals sampled from 19
      worldwide taurine and indicine breeds, plus two outgroup species (Anoa and Water
      Buffalo). Within the larger set of SNPs we targeted 101 high density regions
      spanning up to 7.6 Mb with an average density of approximately one SNP per 4 kb,
      and characterized the linkage disequilibrium (LD) and haplotype block structure
      within individual breeds and groups of breeds in relation to their geographic
      origin and use. RESULTS: From the 101 targeted high-density regions on bovine
      chromosomes 6, 14, and 25, between 57 and 95% of the SNPs were informative in the
      individual breeds. The regions of high LD extend up to ~100 kb and the size of
      haplotype blocks ranges between 30 bases and 75 kb (10.3 kb average). On the
      scale from 1-100 kb the extent of LD and haplotype block structure in cattle has
      high similarity to humans. The estimation of effective population sizes over the
      previous 10,000 generations conforms to two main events in cattle history: the
      initiation of cattle domestication (~12,000 years ago), and the intensification
      of population isolation and current population bottleneck that breeds have
      experienced worldwide within the last ~700 years. Haplotype block density
      correlation, block boundary discordances, and haplotype sharing analyses were
      consistent in revealing unexpected similarities between some beef and dairy
      breeds, making them non-differentiable. Clustering techniques permitted grouping
      of breeds into different clades given their similarities and dissimilarities in
      genetic structure. CONCLUSION: This work presents the first high-resolution
      analysis of haplotype block structure in worldwide cattle samples. Several novel
      results were obtained. First, cattle and human share a high similarity in LD and
      haplotype block structure on the scale of 1-100 kb. Second, unexpected
      similarities in haplotype block structure between dairy and beef breeds make them
      non-differentiable. Finally, our findings suggest that ~30,000 uniformly
      distributed SNPs would be necessary to construct a complete genome LD map in Bos
      taurus breeds, and ~580,000 SNPs would be necessary to characterize the haplotype
      block structure across the complete cattle genome.

PMID- 19393055
TI  - Gene synteny comparisons between different vertebrates provide new insights into
      breakage and fusion events during mammalian karyotype evolution.
AB  - BACKGROUND: Genome comparisons have made possible the reconstruction of the
      eutherian ancestral karyotype but also have the potential to provide new insights
      into the evolutionary inter-relationship of the different eutherian orders within
      the mammalian phylogenetic tree. Such comparisons can additionally reveal (i) the
      nature of the DNA sequences present within the evolutionary breakpoint regions
      and (ii) whether or not the evolutionary breakpoints occur randomly across the
      genome. Gene synteny analysis (E-painting) not only greatly reduces the
      complexity of comparative genome sequence analysis but also extends its
      evolutionary reach. RESULTS: E-painting was used to compare the genome sequences
      of six different mammalian species and chicken. A total of 526 evolutionary
      breakpoint intervals were identified and these were mapped to a median resolution
      of 120 kb, the highest level of resolution so far obtained. A marked correlation
      was noted between evolutionary breakpoint frequency and gene density. This
      correlation was significant not only at the chromosomal level but also sub
      chromosomally when comparing genome intervals of lengths as short as 40 kb.
      Contrary to previous findings, a comparison of evolutionary breakpoint locations
      with the chromosomal positions of well mapped common fragile sites and cancer
      associated breakpoints failed to reveal any evidence for significant co-location.
      Primate-specific chromosomal rearrangements were however found to occur
      preferentially in regions containing segmental duplications and copy number
      variants. CONCLUSION: Specific chromosomal regions appear to be prone to
      recurring rearrangement in different mammalian lineages ('breakpoint reuse') even
      if the breakpoints themselves are likely to be non-identical. The putative
      ancestral eutherian genome, reconstructed on the basis of the synteny analysis of
      7 vertebrate genome sequences, not only confirmed the results of previous
      molecular cytogenetic studies but also increased the definition of the inferred
      structure of ancestral eutherian chromosomes. For the first time in such an
      analysis, the opossum was included as an outgroup species. This served to confirm
      our previous model of the ancestral eutherian genome since all ancestral syntenic
      segment associations were also noted in this marsupial.

PMID- 19393057
TI  - Salivary VEGF: a non-invasive angiogenic and lymphangiogenic proxy in head and
      neck cancer prognostication.
AB  - BACKGROUND: Saliva is an enriched milieu containing biologically active proteins,
      including growth factors and cytokines. The endothelial growth factor family of
      proteins is important for the development of blood and lymphatic vessels in a
      healthy individual but also can aide tumour growth.The aim of this study is to
      develop an independent normative database of values of salivary VEGF in a healthy
      population and to test the hypothesis that values would be raised in the saliva
      of patients with oral cancer. METHODS: Twenty-one participants (12 males and 9
      females) of whom 14 were healthy and 7 had oral squamous cell carcinoma took part
      in this study.An immunoassay was employed to quantify a range of specific
      vascular endothelial and lymphatic endothelial growth factors in various body
      fluid compartments (blood, saliva). This was correlated to tumour factors and
      patient outcomes. RESULTS: The mean salivary levels and serum VEGF A165 levels
      were significantly correlated in the sample as a whole. Additionally, both saliva
      and serum VEGF A165 levels were significantly correlated with age. There were
      significant differences in the salivary and serum levels of the control group and
      the cancer group. CONCLUSION: We present independent normative data on the levels
      of endothelial growth factor in the saliva of a healthy control population. We
      also suggest the use of simple non-invasive tests in helping to predict head and
      neck tumour biology and outcomes.

PMID- 19393056
TI  - A high resolution RH map of the bovine major histocompatibility complex.
AB  - BACKGROUND: The cattle MHC is termed the bovine leukocyte antigen (BoLA) and,
      along with the MHCs of other ruminants, is unique in its genomic organization.
      Consequently, correct and reliable gene maps and sequence information are
      critical to the study of the BoLA region. The bovine genome sequencing project
      has produced two assemblies (Btau_3.1 and 4.0) that differ substantially from
      each other and from conventional gene maps in the BoLA region. To independently
      compare the accuracies of the different sequence assemblies, we have generated a
      high resolution map of BoLA using a 12,000rad radiation hybrid panel. Seventy
      seven unique sequence tagged site (STS) markers chosen at approximately 50 kb
      intervals from the Btau 2.0 assembly and spanning the IIa-III-I and IIb regions
      of the bovine MHC were mapped on a 12,000rad bovine radiation hybrid (RH) panel
      to evaluate the different assemblies of the bovine genome sequence. RESULTS:
      Analysis of the data generated a high resolution RH map of BoLA that was
      significantly different from the Btau_3.1 assembly of the bovine genome but in
      good agreement with the Btau_4.0 assembly. Of the few discordancies between the
      RH map and Btau_4.0, most could be attributed to closely spaced markers that
      could not be precisely ordered in the RH panel. One probable incorrectly
      assembled sequence and three missing sequences were noted in the Btau_4.0
      assembly. The RH map of BoLA is also highly concordant with the sequence-based
      map of HLA (NCBI build 36) when reordered to account for the ancestral inversion
      in the ruminant MHC. CONCLUSION: These results strongly suggest that studies
      using Btau_3.1 for analyses of the BoLA region should be reevaluated in light of
      the Btau_4.0 assembly and indicate that additional research is needed to produce
      a complete assembly of the BoLA genomic sequences.

PMID- 19393058
TI  - Functional genomics of HMGN3a and SMARCAL1 in early mammalian embryogenesis.
AB  - BACKGROUND: Embryonic genome activation (EGA) is a critical event for the
      preimplantation embryo, which is manifested by changes in chromatin structure,
      transcriptional machinery, expression of embryonic genes, and degradation of
      maternal transcripts. The objectives of this study were to determine transcript
      abundance of HMGN3a and SMARCAL1 in mature bovine oocytes and early bovine
      embryos, to perform comparative functional genomics analysis of these genes
      across mammals. RESULTS: New annotations of both HMGN3a and SMARCAL1 were
      submitted to the Bovine Genome Annotation Submission Database at
      BovineGenome.org. Careful analysis of the bovine SMARCAL1 consensus gene set for
      this protein (GLEAN_20241) showed that the NCBI protein contains sequencing
      errors, and that the actual bovine protein has a high degree of homology to the
      human protein. Our results showed that there was a high degree of structural
      conservation of HMGN3a and SMARCAL1 in the mammalian species studied. HMGN3a
      transcripts were present at similar levels in bovine matured oocytes and 2-4-cell
      embryos but at higher levels in 8-16-cell embryos, morulae and blastocysts. On
      the other hand, transcript levels of SMARCAL1 decreased throughout
      preimplantation development. CONCLUSION: The high levels of structural
      conservation of these proteins highlight the importance of chromatin remodeling
      in the regulation of gene expression, particularly during early mammalian
      embryonic development. The greater similarities of human and bovine HMGN3a and
      SMARCAL1 proteins may suggest the cow as a valuable model to study chromatin
      remodeling at the onset of mammalian development. Understanding the roles of
      chromatin remodeling proteins during embryonic development emphasizes the
      importance of epigenetics and could shed light on the underlying mechanisms of
      early mammalian development.

PMID- 19393059
TI  - QTL global meta-analysis: are trait determining genes clustered?
AB  - BACKGROUND: A key open question in biology is if genes are physically clustered
      with respect to their known functions or phenotypic effects. This is of
      particular interest for Quantitative Trait Loci (QTL) where a QTL region could
      contain a number of genes that contribute to the trait being measured. RESULTS:
      We observed a significant increase in gene density within QTL regions compared to
      non-QTL regions and/or the entire bovine genome. By grouping QTL from the Bovine
      QTL Viewer database into 8 categories of non-redundant regions, we have been able
      to analyze gene density and gene function distribution, based on Gene Ontology
      (GO) with relation to their location within QTL regions, outside of QTL regions
      and across the entire bovine genome. We identified a number of GO terms that were
      significantly over represented within particular QTL categories. Furthermore,
      select GO terms expected to be associated with the QTL category based on common
      biological knowledge have also proved to be significantly over represented in QTL
      regions. CONCLUSION: Our analysis provides evidence of over represented GO terms
      in QTL regions. This increased GO term density indicates possible clustering of
      gene functions within QTL regions of the bovine genome. Genes with similar
      functions may be grouped in specific locales and could be contributing to QTL
      traits. Moreover, we have identified over-represented GO terminology that from a
      biological standpoint, makes sense with respect to QTL category type.

PMID- 19393060
TI  - Characterization of the bovine pregnancy-associated glycoprotein gene family-
      analysis of gene sequences, regulatory regions within the promoter and expression
      of selected genes.
AB  - BACKGROUND: The Pregnancy-associated glycoproteins (PAGs) belong to a large
      family of aspartic peptidases expressed exclusively in the placenta of species in
      the Artiodactyla order. In cattle, the PAG gene family is comprised of at least
      22 transcribed genes, as well as some variants. Phylogenetic analyses have shown
      that the PAG family segregates into 'ancient' and 'modern' groupings. Along with
      sequence differences between family members, there are clear distinctions in
      their spatio-temporal distribution and in their relative level of expression. In
      this report, 1) we performed an in silico analysis of the bovine genome to
      further characterize the PAG gene family, 2) we scrutinized proximal promoter
      sequences of the PAG genes to evaluate the evolution pressures operating on them
      and to identify putative regulatory regions, 3) we determined relative transcript
      abundance of selected PAGs during pregnancy and, 4) we performed preliminary
      characterization of the putative regulatory elements for one of the candidate
      PAGs, bovine (bo) PAG-2. RESULTS: From our analysis of the bovine genome, we
      identified 18 distinct PAG genes and 14 pseudogenes. We observed that the first
      500 base pairs upstream of the translational start site contained multiple
      regions that are conserved among all boPAGs. However, a preponderance of
      conserved regions, that harbor recognition sites for putative transcriptional
      factors (TFs), were found to be unique to the modern boPAG grouping, but not the
      ancient boPAGs. We gathered evidence by means of Q-PCR and screening of EST
      databases to show that boPAG-2 is the most abundant of all boPAG transcripts.
      Finally, we provided preliminary evidence for the role of ETS- and DDVL-related
      TFs in the regulation of the boPAG-2 gene. CONCLUSION: PAGs represent a
      relatively large gene family in the bovine genome. The proximal promoter regions
      of these genes display differences in putative TF binding sites, likely
      contributing to observed differences in spatial and temporal expression. We also
      discovered that boPAG-2 is the most abundant of all boPAG transcripts and
      provided evidence for the role of ETS and DDVL TFs in its regulation. These
      experiments mark the crucial first step in discerning the complex transcriptional
      regulation operating within the boPAG gene family.

PMID- 19393061
TI  - Novel transcripts discovered by mining genomic DNA from defined regions of bovine
      chromosome 6.
AB  - BACKGROUND: Linkage analyses strongly suggest a number of QTL for production,
      health and conformation traits in the middle part of bovine chromosome 6 (BTA6).
      The identification of the molecular background underlying the genetic variation
      at the QTL and subsequent functional studies require a well-annotated gene
      sequence map of the critical QTL intervals. To complete the sequence map of the
      defined subchromosomal regions on BTA6 poorly covered with comparative gene
      information, we focused on targeted isolation of transcribed sequences from
      bovine bacterial artificial chromosome (BAC) clones mapped to the QTL intervals.
      RESULTS: Using the method of exon trapping, 92 unique exon trapping sequences
      (ETS) were discovered in a chromosomal region of poor gene coverage. Sequence
      identity to the current NCBI sequence assembly for BTA6 was detected for 91% of
      unique ETS. Comparative sequence similarity search revealed that 11% of the
      isolated ETS displayed high similarity to genomic sequences located on the
      syntenic chromosomes of the human and mouse reference genome assemblies. Nearly a
      third of the ETS identified similar equivalent sequences in genomic sequence
      scaffolds from the alternative Celera-based sequence assembly of the human
      genome. Screening gene, EST, and protein databases detected 17% of ETS with
      identity to known transcribed sequences. Expression analysis of a subset of the
      ETS showed that most ETS (84%) displayed a distinctive expression pattern in a
      multi-tissue panel of a lactating cow verifying their existence in the bovine
      transcriptome. CONCLUSION: The results of our study demonstrate that the exon
      trapping method based on region-specific BAC clones is very useful for targeted
      screening for novel transcripts located within a defined chromosomal region being
      deficiently endowed with annotated gene information. The majority of identified
      ETS represents unknown noncoding sequences in intergenic regions on BTA6
      displaying a distinctive tissue-specific expression profile. However, their
      definite regulatory function has to be analyzed in further studies. The novel
      transcripts will add new sequence information to annotate a complete bovine
      genome sequence assembly, contribute to establish a detailed transcription map
      for targeted BTA6 regions and will also be helpful to dissect of the molecular
      and regulatory background of the QTL detected on BTA6.

PMID- 19393062
TI  - Characterization of the bovine type I IFN locus: rearrangements, expansions, and
      novel subfamilies.
AB  - BACKGROUND: The Type I interferons (IFN) have major roles in the innate immune
      response to viruses, a function that is believed to have led to expansion in the
      number and complexity of their genes, although these genes have remained confined
      to single chromosomal region in all mammals so far examined. IFNB and IFNE define
      the limits of the locus, with all other Type I IFN genes except IFNK distributed
      between these boundaries, strongly suggesting that the locus has broadened as IFN
      genes duplicated and then evolved into a series of distinct families. RESULTS:
      The Type I IFN locus in Bos taurus has undergone significant rearrangement and
      expansion compared to mouse and human, however, with the constituent genes
      separated into two sub-loci separated by >700 kb. The IFNW family is greatly
      expanded, comprising 24 potentially functional genes and at least 8 pseudogenes.
      The IFNB (n = 6), represented in human and mouse by one copy, are also present as
      multiple copies in Bos taurus. The IFNT, which encode a non-virally inducible,
      ruminant-specific IFN secreted by the pre-implantation conceptus, are represented
      by three genes and two pseudogenes. The latter have sequences intermediate
      between IFNT and IFNW. A new Type I IFN family (IFNX) of four members, one of
      which is a pseudogene, appears to have diverged from the IFNA lineage at least 83
      million years ago, but is absent in all other sequenced genomes with the possible
      exception of the horse, a non-ruminant herbivore. CONCLUSION: In summary, we have
      provided the first comprehensive annotation of the Type I IFN locus in Bos
      taurus, thereby providing an insight into the functional evolution of the Type I
      IFN in ruminants. The diversity and global spread of the ruminant species may
      have required an expansion of the Type I IFN locus and its constituent genes to
      provide broad anti-viral protection required for foraging and foregut
      fermentation.

PMID- 19393063
TI  - Analysis of the complement and molecular evolution of tRNA genes in cow.
AB  - BACKGROUND: Detailed information regarding the number and organization of
      transfer RNA (tRNA) genes at the genome level is becoming readily available with
      the increase of DNA sequencing of whole genomes. However the identification of
      functional tRNA genes is challenging for species that have large numbers of
      repetitive elements containing tRNA derived sequences, such as Bos taurus.
      Reliable identification and annotation of entire sets of tRNA genes allows the
      evolution of tRNA genes to be understood on a genomic scale. RESULTS: In this
      study, we explored the B. taurus genome using bioinformatics and comparative
      genomics approaches to catalogue and analyze cow tRNA genes. The initial analysis
      of the cow genome using tRNAscan-SE identified 31,868 putative tRNA genes and
      189,183 pseudogenes, where 28,830 of the 31,868 predicted tRNA genes were
      classified as repetitive elements by the RepeatMasker program. We then used
      comparative genomics to further discriminate between functional tRNA genes and
      tRNA-derived sequences for the remaining set of 3,038 putative tRNA genes. For
      our analysis, we used the human, chimpanzee, mouse, rat, horse, dog, chicken and
      fugu genomes to predict that the number of active tRNA genes in cow lies in the
      vicinity of 439. Of this set, 150 tRNA genes were 100% identical in their
      sequences across all nine vertebrate genomes studied. Using clustering analyses,
      we identified a new tRNA-GlyCCC subfamily present in all analyzed mammalian
      genomes. We suggest that this subfamily originated from an ancestral tRNA-GlyGCC
      gene via a point mutation prior to the radiation of the mammalian lineages.
      Lastly, in a separate analysis we created phylogenetic profiles for each putative
      cow tRNA gene using a representative set of genomes to gain an overview of common
      evolutionary histories of tRNA genes. CONCLUSION: The use of a combination of
      bioinformatics and comparative genomics approaches has allowed the confident
      identification of a set of cow tRNA genes that will facilitate further studies in
      understanding the molecular evolution of cow tRNA genes.

PMID- 19393064
TI  - Birth weight and characteristics of endothelial and smooth muscle cell cultures
      from human umbilical cord vessels.
AB  - BACKGROUND: Low birth weight has been related to an increased risk for developing
      high blood pressure in adult life. The molecular and cellular analysis of
      umbilical cord artery and vein may provide information about the early vascular
      characteristics of an individual. We have assessed several phenotype
      characteristics of the four vascular cell types derived from human umbilical
      cords of newborns with different birth weight. Further follow-up studies could
      show the association of those vascular properties with infancy and adulthood
      blood pressure. METHODS: Endothelial and smooth muscle cell cultures were
      obtained from umbilical cords from two groups of newborns of birth weight less
      than 2.8 kg or higher than 3.5 kg. The expression of specific endothelial cell
      markers (von Willebrand factor, CD31, and the binding and internalization of
      acetylated low-density lipoprotein) and the smooth muscle cell specific alpha
      actin have been evaluated. Cell culture viability, proliferation kinetic, growth
      fraction (expression of Ki67) and percentage of senescent cells (detection of
      beta-galactosidase activity at pH 6.0) have been determined. Endothelial cell
      projection area was determined by morphometric analysis of cell cultures after
      CD31 immunodetection. RESULTS: The highest variation was found in cell density at
      the confluence of endothelial cell cultures derived from umbilical cord arteries
      (66,789 +/- 5,093 cells/cm(2) vs. 45,630 +/- 11,927 cells/cm(2), p < 0.05).
      Morphometric analysis indicated that the projection area of the artery
      endothelial cells (1,161 +/- 198 and 1,544 +/- 472 microm(2), p < 0.05), but not
      those derived from the vein from individuals with a birth weight lower than 2.8
      kg was lower than that of cells from individuals with a birth weight higher than
      3.5 kg. CONCLUSION: The analysis of umbilical cord artery endothelial cells,
      which demonstrated differences in cell size related to birth weight, can provide
      hints about the cellular and molecular links between lower birth weight and
      increased adult high blood pressure risk.

PMID- 19393065
TI  - Cross-species mapping of bidirectional promoters enables prediction of
      unannotated 5' UTRs and identification of species-specific transcripts.
AB  - BACKGROUND: Bidirectional promoters are shared regulatory regions that influence
      the expression of two oppositely oriented genes. This type of regulatory
      architecture is found more frequently than expected by chance in the human
      genome, yet many specifics underlying the regulatory design are unknown. Given
      that the function of most orthologous genes is similar across species, we
      hypothesized that the architecture and regulation of bidirectional promoters
      might also be similar across species, representing a core regulatory structure
      and enabling annotation of these regions in additional mammalian genomes.
      RESULTS: By mapping the intergenic distances of genes in human, chimpanzee,
      bovine, murine, and rat, we show an enrichment for pairs of genes equal to or
      less than 1,000 bp between their adjacent 5' ends ("head-to-head") compared to
      pairs of genes that fall in the same orientation ("head-to-tail") or whose 3'
      ends are side-by-side ("tail-to-tail"). A representative set of 1,369 human
      bidirectional promoters was mapped to orthologous sequences in other mammals. We
      confirmed predictions for 5' UTRs in nine of ten manual picks in bovine based on
      comparison to the orthologous human promoter set and in six of seven predictions
      in human based on comparison to the bovine dataset. The two predictions that did
      not have orthology as bidirectional promoters in the other species resulted from
      unique events that initiated transcription in the opposite direction in only
      those species. We found evidence supporting the independent emergence of
      bidirectional promoters from the family of five RecQ helicase genes, which gained
      their bidirectional promoters and partner genes independently rather than through
      a duplication process. Furthermore, by expanding our comparisons from pairwise to
      multispecies analyses we developed a map representing a core set of bidirectional
      promoters in mammals. CONCLUSION: We show that the orthologous positions of
      bidirectional promoters provide a reliable guide to directly annotate over one
      thousand regulatory regions in sequences of mammalian genomes, while also serving
      as a useful tool to predict 5' UTR positions and identify genes that are novel to
      a single species.

PMID- 19393066
TI  - Transcriptional reprogramming of gene expression in bovine somatic cell chromatin
      transfer embryos.
AB  - BACKGROUND: Successful reprogramming of a somatic genome to produce a healthy
      clone by somatic cells nuclear transfer (SCNT) is a rare event and the mechanisms
      involved in this process are poorly defined. When serial or successive rounds of
      cloning are performed, blastocyst and full term development rates decline even
      further with the increasing rounds of cloning. Identifying the "cumulative
      errors" could reveal the epigenetic reprogramming blocks in animal cloning.
      RESULTS: Bovine clones from up to four generations of successive cloning were
      produced by chromatin transfer (CT). Using Affymetrix bovine microarrays we
      determined that the transcriptomes of blastocysts derived from the first and the
      fourth rounds of cloning (CT1 and CT4 respectively) have undergone an extensive
      reprogramming and were more similar to blastocysts derived from in vitro
      fertilization (IVF) than to the donor cells used for the first and the fourth
      rounds of chromatin transfer (DC1 and DC4 respectively). However a set of
      transcripts in the cloned embryos showed a misregulated pattern when compared to
      IVF embryos. Among the genes consistently upregulated in both CT groups compared
      to the IVF embryos were genes involved in regulation of cytoskeleton and cell
      shape. Among the genes consistently upregulated in IVF embryos compared to both
      CT groups were genes involved in chromatin remodelling and stress coping.
      CONCLUSION: The present study provides a data set that could contribute in our
      understanding of epigenetic errors in somatic cell chromatin transfer.
      Identifying "cumulative errors" after serial cloning could reveal some of the
      epigenetic reprogramming blocks shedding light on the reprogramming process,
      important for both basic and applied research.

PMID- 19393067
TI  - Genomic organization and classification of the bovine WC1 genes and expression by
      peripheral blood gamma delta T cells.
AB  - BACKGROUND: WC1 co-receptors are group B scavenger receptor cysteine-rich
      molecules that are found exclusively on gammadeltaT cells and are thought to be
      encoded by a multi-gene family. Previous studies have shown gammadeltaT cells
      that respond to a particular stimulus have unique WC1 molecules expressed. Prior
      to the onset of the studies described here only one full-length WC1 nucleotide
      sequence was publicly available, though three WC1 molecules had been
      distinguished based on monoclonal antibody reactivity. Furthermore, the number of
      WC1 genes found in the bovine genome and their sequences had not yet been
      resolved. RESULTS: By annotating the bovine genome Btau_3.1 assembly, here we
      show the existence of 13 members in the WC1 gene family and their organization
      within two loci on chromosome 5 including three distinct exon-intron gene
      structures one of which coded for a potentially more primitive and smaller WC1
      molecule that is similar to the swine WC1 gene. We also provide cDNA evidence as
      verification for many of the annotated sequences and show transcripts for
      isoforms derived by alternative splicing. CONCLUSION: It is possible that WC1
      diversity contributes to functional differences that have been observed between
      gammadeltaT cell populations. The studies described here demonstrate that WC1
      molecules are encoded by a large, multi-gene family whose transcripts undergo
      extensive alternative splicing. Similar to other non-rearranging immunoreceptors,
      it is likely that the WC1 gene repertoire underwent expansion in order to keep
      pace with rapidly changing ligands.

PMID- 19393069
TI  - Cardiocladius oliffi (Diptera: Chironomidae) as a potential biological control
      agent against Simulium squamosum (Diptera: Simuliidae).
AB  - BACKGROUND: The control of onchocerciasis in the African region is currently
      based mainly on the mass drug administration of ivermectin. Whilst this has been
      found to limit morbidity, it does not stop transmission. In the absence of a
      macrofilaricide, there is a need for an integrated approach for disease
      management, which includes vector control. Vector control using chemical
      insecticides is expensive to apply, and therefore the use of other measures such
      as biological control agents is needed. Immature stages of Simulium squamosum,
      reared in the laboratory from egg masses collected from the field at Boti Falls
      and Huhunya (River Pawnpawn) in Ghana, were observed to be attacked and fed upon
      by larvae of the chironomid Cardiocladius oliffi Freeman, 1956 (Diptera:
      Chironomidae). METHODS: Cardiocladius oliffi was successfully reared in the
      rearing system developed for S. damnosum s.l. and evaluated for its importance as
      a biological control agent in the laboratory. RESULTS: Even at a ratio of one C.
      oliffi to five S. squamosum, they caused a significant decrease in the number of
      adult S. squamosum emerging from the systems (treatments). Predation was
      confirmed by the amplification of Simulium DNA from C. oliffi observed to have
      fed on S. squamosum pupae. The study also established that the chironomid flies
      could successfully complete their development on a fish food diet only.
      CONCLUSION: Cardiocladius oliffi has been demonstrated as potential biological
      control agent against S. squamosum.

PMID- 19393068
TI  - Genomic analysis reveals extensive gene duplication within the bovine TRB locus.
AB  - BACKGROUND: Diverse TR and IG repertoires are generated by V(D)J somatic
      recombination. Genomic studies have been pivotal in cataloguing the V, D, J and C
      genes present in the various TR/IG loci and describing how duplication events
      have expanded the number of these genes. Such studies have also provided insights
      into the evolution of these loci and the complex mechanisms that regulate TR/IG
      expression. In this study we analyze the sequence of the third bovine genome
      assembly to characterize the germline repertoire of bovine TRB genes and compare
      the organization, evolution and regulatory structure of the bovine TRB locus with
      that of humans and mice. RESULTS: The TRB locus in the third bovine genome
      assembly is distributed over 5 scaffolds, extending to approximately 730 Kb. The
      available sequence contains 134 TRBV genes, assigned to 24 subgroups, and 3
      clusters of DJC genes, each comprising a single TRBD gene, 5-7 TRBJ genes and a
      single TRBC gene. Seventy-nine of the TRBV genes are predicted to be functional.
      Comparison with the human and murine TRB loci shows that the gene order, as well
      as the sequences of non-coding elements that regulate TRB expression, are highly
      conserved in the bovine. Dot-plot analyses demonstrate that expansion of the
      genomic TRBV repertoire has occurred via a complex and extensive series of
      duplications, predominantly involving DNA blocks containing multiple genes. These
      duplication events have resulted in massive expansion of several TRBV subgroups,
      most notably TRBV6, 9 and 21 which contain 40, 35 and 16 members respectively.
      Similarly, duplication has lead to the generation of a third DJC cluster.
      Analyses of cDNA data confirms the diversity of the TRBV genes and, in addition,
      identifies a substantial number of TRBV genes, predominantly from the larger
      subgroups, which are still absent from the genome assembly. The observed gene
      duplication within the bovine TRB locus has created a repertoire of
      phylogenetically diverse functional TRBV genes, which is substantially larger
      than that described for humans and mice. CONCLUSION: The analyses completed in
      this study reveal that, although the gene content and organization of the bovine
      TRB locus are broadly similar to that of humans and mice, multiple duplication
      events have led to a marked expansion in the number of TRB genes. Similar
      expansions in other ruminant TR loci suggest strong evolutionary pressures in
      this lineage have selected for the development of enlarged sets of TR genes that
      can contribute to diverse TR repertoires.

PMID- 19393070
TI  - Unlocking the bovine genome.
AB  - The draft genome sequence of cattle (Bos taurus) has now been analyzed by the
      Bovine Genome Sequencing and Analysis Consortium and the Bovine HapMap
      Consortium, which together represent an extensive collaboration involving more
      than 300 scientists from 25 different countries.

PMID- 19393071
TI  - Granger causality vs. dynamic Bayesian network inference: a comparative study.
AB  - BACKGROUND: In computational biology, one often faces the problem of deriving the
      causal relationship among different elements such as genes, proteins,
      metabolites, neurons and so on, based upon multi-dimensional temporal data.
      Currently, there are two common approaches used to explore the network structure
      among elements. One is the Granger causality approach, and the other is the
      dynamic Bayesian network inference approach. Both have at least a few thousand
      publications reported in the literature. A key issue is to choose which approach
      is used to tackle the data, in particular when they give rise to contradictory
      results. RESULTS: In this paper, we provide an answer by focusing on a systematic
      and computationally intensive comparison between the two approaches on both
      synthesized and experimental data. For synthesized data, a critical point of the
      data length is found: the dynamic Bayesian network outperforms the Granger
      causality approach when the data length is short, and vice versa. We then test
      our results in experimental data of short length which is a common scenario in
      current biological experiments: it is again confirmed that the dynamic Bayesian
      network works better. CONCLUSION: When the data size is short, the dynamic
      Bayesian network inference performs better than the Granger causality approach;
      otherwise the Granger causality approach is better.

PMID- 19393072
TI  - Application of GC-MS for the detection of lipophilic compounds in diverse plant
      tissues.
AB  - BACKGROUND: The concept of metabolite profiling has been around for decades and
      technical innovations are now enabling it to be carried out on a large scale with
      respect to the number of both metabolites measured and experiments carried out.
      However, studies are generally confined to polar compounds alone. Here we
      describe a simple method for lipophilic compounds analysis in various plant
      tissues. RESULTS: We choose the same preparative and instrumental platform for
      lipophilic profiling as that we routinely use for polar metabolites measurements.
      The method was validated in terms of linearity, carryover, reproducibility and
      recovery rates, as well as using various plant tissues.As a first case study we
      present metabolic profiling of Arabidopsis root and shoot tissue of wild type
      (C24) and mutant (rsr4-1) plants deficient on vitamin B6. We found significant
      alterations in lipid constituent contents, especially in the roots, which were
      characterised by dramatic increases in several fatty acids, thus providing
      further hint for the role of pyridoxine in oxidative stress and lipid
      peroxidation.The second example is the lipophilic profiling of red and green
      tomato fruit cuticles of wild type (Alisa Craig) and the DFD (delayed fruit
      deterioration) mutant, which we compared and contrasted with the more focused wax
      analysis of these plants reported before. CONCLUSION: We can rapidly and reliably
      detect and quantify over 40 lipophilic metabolites including fatty acids, fatty
      alcohols, alkanes, sterols and tocopherols. The method presented here affords a
      simple and rapid, yet robust complement to previously validated methods of polar
      metabolite profiling by gas-chromatography mass-spectrometry.

PMID- 19393073
TI  - Evidence-based practice in neonatal health: knowledge among primary health care
      staff in northern Viet Nam.
AB  - BACKGROUND: An estimated four million deaths occur each year among children in
      the neonatal period. Current evidence-based interventions could prevent a large
      proportion of these deaths. However, health care workers involved in neonatal
      care need to have knowledge regarding such practices before being able to put
      them into action.The aim of this survey was to assess the knowledge of primary
      health care practitioners regarding basic, evidence-based procedures in neonatal
      care in a Vietnamese province. A further aim was to investigate whether
      differences in level of knowledge were linked to certain characteristics of
      community health centres, such as access to national guidelines in reproductive
      health care, number of assisted deliveries and geographical location. METHODS:
      This cross-sectional survey was completed within a baseline study preparing for
      an intervention study on knowledge translation (Implementing knowledge into
      practice for improved neonatal survival: a community-based trial in Quang Ninh
      province, Viet Nam, the NeoKIP project, ISRCTN44599712). Sixteen multiple-choice
      questions from five basic areas of evidence-based practice in neonatal care were
      distributed to 155 community health centres in 12 districts in a Vietnamese
      province, reaching 412 primary health care workers. RESULTS: All health care
      workers approached for the survey responded. Overall, they achieved 60% of the
      maximum score of the questionnaire. Staff level of knowledge on evidence-based
      practice was linked to the geographical location of the CHC, but not to access to
      the national guidelines or the number of deliveries at the community level. Two
      separated geographical areas were identified with differences in staff level of
      knowledge and concurrent differences in neonatal survival, antenatal care and
      postnatal home visits. CONCLUSION: We have identified a complex pattern of
      associations between knowledge, geography, demographic factors and neonatal
      outcomes. Primary health care staff knowledge regarding neonatal health is
      scarce. This is a factor that is possible to influence and should be considered
      in future efforts for improving the neonatal health situation in Viet Nam.

PMID- 19393074
TI  - Quantitation of DNA methylation by melt curve analysis.
AB  - BACKGROUND: Methylation of DNA is a common mechanism for silencing genes, and
      aberrant methylation is increasingly being implicated in many diseases such as
      cancer. There is a need for robust, inexpensive methods to quantitate methylation
      across a region containing a number of CpGs. We describe and validate a rapid, in
      tube method to quantitate DNA methylation using the melt data obtained following
      amplification of bisulfite modified DNA in a real-time thermocycler. METHODS: We
      first describe a mathematical method to normalise the raw fluorescence data
      generated by heating the amplified bisulfite modified DNA. From this normalised
      data the temperatures at which melting begins and finishes can be calculated,
      which reflect the less and more methylated template molecules present
      respectively. Also the T50, the temperature at which half the amplicons are
      melted, which represents the summative methylation of all the CpGs in the
      template mixture, can be calculated. These parameters describe the methylation
      characteristics of the region amplified in the original sample. RESULTS: For
      validation we used synthesized oligonucleotides and DNA from fresh cells and
      formalin fixed paraffin embedded tissue, each with known methylation. Using our
      quantitation we could distinguish between unmethylated, partially methylated and
      fully methylated oligonucleotides mixed in varying ratios. There was a linear
      relationship between T50 and the dilution of methylated into unmethylated DNA. We
      could quantitate the change in methylation over time in cell lines treated with
      the demethylating drug 5-aza-2'-deoxycytidine, and the differences in methylation
      associated with complete, clonal or no loss of MGMT expression in formalin fixed
      paraffin embedded tissues. CONCLUSION: We have validated a rapid, simple in-tube
      method to quantify methylation which is robust and reproducible, utilizes easily
      designed primers and does not need proprietary algorithms or software. The
      technique does not depend on any operator manipulation or interpretation of the
      melt curves, and is suitable for use in any laboratory with a real-time
      thermocycler. The parameters derived provide an objective description and
      quantitation of the methylation in a specimen, and can be used to for statistical
      comparisons of methylation between specimens.

PMID- 19393076
TI  - Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma
      of the breast.
AB  - BACKGROUND: Extramedullary plasmacytomas are seldom solitary and usually progress
      to diffuse myelomatosis. Plasmacytomas of the breast are rare, especially when
      not associated multiple myeloma. Synchronous infiltrating ductal carcinoma and
      primary extramedullary plasmacytoma of the breast have not previously reported.
      CASE PRESENTATION: A 27-years-old woman with an untreated upper outer quadrant
      breast mass for 1-year was referred to our cancer hospital for surgical
      evaluation of increasing breast pain. Postoperatively, microscopic examination
      revealed an infiltrating ductal carcinoma complicated by an extramedullary
      plasmacytoma divided by fibrous tissue in one section. Following surgery, the
      patient received chemotherapy for the carcinoma and radiotherapy for the
      plasmacytoma. CONCLUSION: In this case, careful histopathology examination was
      essential to make the correct diagnosis and therapy for these synchronous
      lesions. The patient finished chemotherapy and radiotherapy without significant
      adverse effects.

PMID- 19393077
TI  - Association between the NBS1 E185Q polymorphism and cancer risk: a meta-analysis.
AB  - BACKGROUND: NBS1 is a key DNA repair protein in the homologous recombination
      repair pathway and a signal modifier in the intra-S phase checkpoint that plays
      important roles in maintaining genomic stability. The NBS1 8360G>C (Glu185Gln) is
      one of the most commonly studied polymorphisms of the gene for their association
      with risk of cancers, but the results are conflicting. METHODS: We performed a
      meta-analysis using 16 eligible case-control studies (including 17 data sets)
      with a total of 9,734 patients and 10,325 controls to summarize the data on the
      association between the NBS1 8360G>C (E185Q) polymorphism and cancer risk.
      RESULTS: Compared with the common 8360GG genotype, the carriers of variant
      genotypes (i.e., 8360 GC/CC) had a 1.06-fold elevated risk of cancer (95% CI =
      1.00-1.12, P = 0.05) in a dominant genetic model as estimated in a fixed effect
      model. However, the association was not found in an additive genetic model (CC vs
      GG) (odds ratio, OR = 0.98, 95% CI = 0.85-1.13, P = 0.78) nor in a recessive
      genetic model (CC vs GC +GG) (OR = 0.94, 95% CI = 0.82-1.07, P = 0.36). The
      effect of the 8360G>C (E185Q) polymorphism was further evaluated in
      stratification analysis. It was demonstrated that the increased risk of cancer
      associated with 8360G>C variant genotypes was more pronounced in the Caucasians
      (OR = 1.07, 95% CI = 1.01-1.14, P = 0.03). CONCLUSION: Our meta-analysis suggests
      that the NBS1 E185Q variant genotypes (8360 GC/CC) might be associated with an
      increased risk of cancer, especially in Caucasians.

PMID- 19393078
TI  - Comparative genomics of Enterococcus faecalis from healthy Norwegian infants.
AB  - BACKGROUND: Enterococcus faecalis, traditionally considered a harmless commensal
      of the intestinal tract, is now ranked among the leading causes of nosocomial
      infections. In an attempt to gain insight into the genetic make-up of commensal
      E. faecalis, we have studied genomic variation in a collection of community
      derived E. faecalis isolated from the feces of Norwegian infants. RESULTS: The E.
      faecalis isolates were first sequence typed by multilocus sequence typing (MLST)
      and characterized with respect to antibiotic resistance and properties associated
      with virulence. A subset of the isolates was compared to the vancomycin resistant
      strain E. faecalis V583 (V583) by whole genome microarray comparison (comparative
      genomic hybridization (CGH)). Several of the putative enterococcal virulence
      factors were found to be highly prevalent among the commensal baby isolates. The
      genomic variation as observed by CGH was less between isolates displaying the
      same MLST sequence type than between isolates belonging to different evolutionary
      lineages. CONCLUSION: The variations in gene content observed among the
      investigated commensal E. faecalis is comparable to the genetic variation
      previously reported among strains of various origins thought to be representative
      of the major E. faecalis lineages. Previous MLST analysis of E. faecalis have
      identified so-called high-risk enterococcal clonal complexes (HiRECC), defined as
      genetically distinct subpopulations, epidemiologically associated with
      enterococcal infections. The observed correlation between CGH and MLST presented
      here, may offer a method for the identification of lineage-specific genes, and
      may therefore add clues on how to distinguish pathogenic from commensal E.
      faecalis. In this work, information on the core genome of E. faecalis is also
      substantially extended.

PMID- 19393079
TI  - Determinants of left ventricular mass in obesity; a cardiovascular magnetic
      resonance study.
AB  - BACKGROUND: Obesity is linked to increased left ventricular mass, an independent
      predictor of mortality. As a result of this, understanding the determinants of
      left ventricular mass in the setting of obesity has both therapeutic and
      prognostic implications. Using cardiovascular magnetic resonance our goal was to
      elucidate the main predictors of left ventricular mass in severely obese subjects
      free of additional cardiovascular risk factors. METHODS: 38 obese (BMI 37.8 +/-
      6.9 kg/m2) and 16 normal weight controls subjects, (BMI 21.7 +/- 1.8 kg/m2), all
      without cardiovascular risk factors, underwent cardiovascular magnetic resonance
      imaging to assess left ventricular mass, left ventricular volumes and visceral
      fat mass. Left ventricular mass was then compared to serum and anthropometric
      markers of obesity linked to left ventricular mass, i.e. height, age, blood
      pressure, total fat mass, visceral fat mass, lean mass, serum leptin and fasting
      insulin level. RESULTS: As expected, obesity was associated with significantly
      increased left ventricular mass (126 +/- 27 vs 90 +/- 20 g; p < 0.001). Stepwise
      multiple regression analysis showed that over 75% of the cross sectional
      variation in left ventricular mass can be explained by lean body mass (beta =
      0.51, p < 0.001), LV stroke volume (beta = 0.31 p = 0.001) and abdominal visceral
      fat mass (beta = 0.20, p = 0.02), all of which showed highly significant
      independent associations with left ventricular mass (overall R2 = 0.77).
      CONCLUSION: The left ventricular hypertrophic response to obesity in the absence
      of additional cardiovascular risk factors is mainly attributable to increases in
      lean body mass, LV stroke volume and visceral fat mass. In view of the well
      documented link between obesity, left ventricular hypertrophy and mortality,
      these findings have potentially important prognostic and therapeutic implications
      for primary and secondary prevention.

PMID- 19393080
TI  - Internationally recruited nurses from India and the Philippines in the United
      Kingdom: the decision to emigrate.
AB  - BACKGROUND: The United Kingdom has recruited nurses from countries with a
      reported surplus in their nursing workforce, such as India and the Philippines.
      However, little is known about the decision to emigrate made by nurses from these
      countries. One theory suggests that individuals weigh the benefits and costs of
      migration: the push and pull factors. This paper challenges the restricted
      economic focus of this predominant theory and compares the diverse motivations of
      nurses from different countries as well as those of nurses with previous
      migratory experience and first-time migrants. METHODS: This research was
      undertaken in a National Health Service acute trust in London by means of a
      qualitative interpretative approach. Data were collected through face-to-face
      longitudinal and cross-sectional interviews with internationally recruited nurses
      from India (n=6) and the Philippines (n=15); and analysis of their narratives was
      used to generate data about their expectations and experiences. Data were
      analysed by means of a framework approach that allowed for intra-case and cross
      case analysis. RESULTS: From an individual perspective, nurses in this study
      reported economic reasons as the main trigger for migration in the first
      instance. Yet this doesn't entirely explain the decision to move from previous
      migratory destinations (e.g. Saudi Arabia) where economic needs are already
      fulfilled. In these cases migration is influenced by professional and social
      aspirations that highlight the influence of the cultural environment-
      specifically some religious and gender-related issues. Family support and support
      from migratory networks in the country of origin and destination were also
      important elements conducive to and supportive of migration. Nurses from India
      report coming to the United Kingdom to stay, while Filipina nurses come as
      temporary migrants sending remittances to support their families in the
      Philippines. CONCLUSION: This study shows the diverse motivations of nurses from
      different countries and with different migratory backgrounds and provides
      evidence that factors other than economic factors influence nurses' decision to
      emigrate. This information can help developing countries increase retention of
      this essential and often scarce resource and can also help the United Kingdom's
      National Health Service to improve the experience of internationally recruited
      nurses and therefore increase their retention in the United Kingdom.

PMID- 19393082
TI  - Do pseudo-absence selection strategies influence species distribution models and
      their predictions? An information-theoretic approach based on simulated data.
AB  - BACKGROUND: Multiple logistic regression is precluded from many practical
      applications in ecology that aim to predict the geographic distributions of
      species because it requires absence data, which are rarely available or are
      unreliable. In order to use multiple logistic regression, many studies have
      simulated "pseudo-absences" through a number of strategies, but it is unknown how
      the choice of strategy influences models and their geographic predictions of
      species. In this paper we evaluate the effect of several prevailing pseudo
      absence strategies on the predictions of the geographic distribution of a virtual
      species whose "true" distribution and relationship to three environmental
      predictors was predefined. We evaluated the effect of using a) real absences b)
      pseudo-absences selected randomly from the background and c) two-step approaches:
      pseudo-absences selected from low suitability areas predicted by either
      Ecological Niche Factor Analysis: (ENFA) or BIOCLIM. We compared how the choice
      of pseudo-absence strategy affected model fit, predictive power, and information
      theoretic model selection results. RESULTS: Models built with true absences had
      the best predictive power, best discriminatory power, and the "true" model (the
      one that contained the correct predictors) was supported by the data according to
      AIC, as expected. Models based on random pseudo-absences had among the lowest
      fit, but yielded the second highest AUC value (0.97), and the "true" model was
      also supported by the data. Models based on two-step approaches had intermediate
      fit, the lowest predictive power, and the "true" model was not supported by the
      data. CONCLUSION: If ecologists wish to build parsimonious GLM models that will
      allow them to make robust predictions, a reasonable approach is to use a large
      number of randomly selected pseudo-absences, and perform model selection based on
      an information theoretic approach. However, the resulting models can be expected
      to have limited fit.

PMID- 19393081
TI  - Exploring the functional interaction between POSH and ALIX and the relevance to
      HIV-1 release.
AB  - BACKGROUND: The ALG2-interacting protein X (ALIX)/AIP1 is an adaptor protein with
      multiple functions in intracellular protein trafficking that plays a central role
      in the biogenesis of enveloped viruses. The ubiquitin E3-ligase POSH (plenty of
      SH3) augments HIV-1 egress by facilitating the transport of Gag to the cell
      membrane. Recently, it was reported, that POSH interacts with ALIX and thereby
      enhances ALIX mediated phenotypes in Drosophila. RESULTS: In this study we
      identified ALIX as a POSH ubiquitination substrate in human cells: POSH induces
      the ubiquitination of ALIX that is modified on several lysine residues in vivo
      and in vitro. This ubiquitination does not destabilize ALIX, suggesting a
      regulatory function. As it is well established that ALIX rescues virus release of
      L-domain mutant HIV-1, HIV-1DeltaPTAP, we demonstrated that wild type POSH, but
      not an ubiquitination inactive RING finger mutant (POSHV14A), substantially
      enhances ALIX-mediated release of infectious virions derived from HIV-1DeltaPTAP
      L-domain mutant (YPXnL-dependent HIV-1). In further agreement with the idea of a
      cooperative function of POSH and ALIX, mutating the YPXnL-ALIX binding site in
      Gag completely abrogated augmentation of virus release by overexpression of POSH.
      However, the effect of the POSH-mediated ubiquitination appears to be auxiliary,
      but not necessary, as silencing of POSH by RNAi does not disturb ALIX
      augmentation of virus release. CONCLUSION: Thus, the cumulative results
      identified ALIX as an ubiquitination substrate of POSH and indicate that POSH and
      ALIX cooperate to facilitate efficient virus release. However, while ALIX is
      obligatory for the release of YPXnL-dependent HIV-1, POSH, albeit rate-limiting,
      may be functionally interchangeable.

PMID- 19393083
TI  - Interleukin-1beta and fibroblast growth factor receptor 1 cooperate to induce
      cyclooxygenase-2 during early mammary tumourigenesis.
AB  - INTRODUCTION: Inflammation within the tumour microenvironment correlates with
      increased invasiveness and poor prognosis in many types of cancer, including
      breast cancer. We have previously demonstrated that activation of a mouse mammary
      tumour virus (MMTV)-driven inducible fibroblast growth factor receptor 1 (iFGFR1)
      transgene in mammary epithelial cells results in an inflammatory response
      characterised by induction of inflammatory genes in the mammary gland.
      Specifically, we have observed increased levels of IL-1beta expression in the
      mammary gland following activation of iFGFR1 and have used the iFGFR1 model to
      elucidate the function of IL-1beta in promoting iFGFR1-induced mammary lesions.
      METHODS: To determine the functional consequences of IL-1beta induction during
      FGFR1-induced mammary tumourigenesis, the effects of IL-1beta inhibition on the
      formation of epithelial hyperplasias were examined using the MMTV-iFGFR1
      transgenic mouse model. Further studies used a combination of the HC-11 mammary
      epithelial cell line that stably expresses iFGFR1 and the MMTV-iFGFR1 transgenic
      mice to further define the mechanisms of IL-1beta function. RESULTS: Inhibition
      of IL-1beta activity in vivo resulted in reduced iFGFR1-induced epithelial
      proliferation and formation of hyperplastic structures. Further studies
      demonstrated that treatment of mammary epithelial cells with IL-1beta-induced
      expression of cyclooxygenase (Cox)-2 both in vitro and in vivo. Finally,
      inhibition of Cox-2 prior to activation of iFGFR1 in the transgenic mice also
      resulted in decreased iFGFR1-induced formation of hyperplastic structures.
      CONCLUSIONS: The results from these studies indicate that targeting the
      inflammatory cytokine IL-1beta partially inhibits iFGFR1-induced formation of
      early-stage mammary lesions, in part through induction of Cox-2. These findings
      demonstrate that activation of a growth factor receptor in mammary epithelial
      cells results in increased expression of inflammatory mediators, which cooperate
      to promote the initiation of hyperplastic lesions in the mammary gland.

PMID- 19393084
TI  - Preventing panic disorder: cost-effectiveness analysis alongside a pragmatic
      randomised trial.
AB  - BACKGROUND: Panic disorder affects many people, is associated with a formidable
      disease burden, and imposes costs on society. The annual influx of new cases of
      panic disorder is substantial. From the public health perspective it may
      therefore be a sound policy to reduce the influx of new cases, to maintain the
      quality of life in many people, and to avoid the economic costs associated with
      the full-blown disorder. For this purpose, prevention is needed. Here we present
      the first economic evaluation of such an intervention. METHODS: Randomised trial
      of 117 people with panic disorder symptoms not meeting the diagnostic criteria of
      DSM-IV panic disorder. The interventions were time-limited cognitive-behavioural
      therapy v care-as-usual. The central clinical endpoint was DSM-IV panic disorder
      free survival over 3 months. Costs were calculated from the societal perspective.
      Using the bootstrap method, incremental cost-effectiveness ratios were obtained,
      placed in 95% confidence intervals, projected on the cost-effectiveness plane,
      and presented as acceptability curves. RESULTS: The median incremental cost
      effectiveness ratio is euro6,198 (95% CI 2,435 - 60,731) per PD-free survival
      gained, which has a likelihood of 75.2% of being more acceptable from a cost
      effectiveness point of view than care-as-usual when a willingness-to-pay ceiling
      is assumed of euro10,000 per PD-free survival. The most significant cost driver
      was therapists' time. A sensitivity analysis indicated that cost-effectiveness
      improves when the number of therapist hours is reduced. CONCLUSION: This is the
      first economic evaluation alongside a prevention trial in panic disorder. The
      small sample (n = 117) and the short time horizon of 3 months preclude firm
      conclusions, but our findings suggest that the intervention may be acceptable
      from a cost-effectiveness point of view, especially when therapist involvement
      can be kept minimal. Nevertheless, our results must await replication in a larger
      trial with longer follow-up times before we can confidently recommend
      implementation of the intervention on a broad scale. In the light of our findings
      and given the burden of panic disorder, such a new trial is well worth the
      effort.

PMID- 19393085
TI  - Choosing the right path: enhancement of biologically relevant sets of genes or
      proteins using pathway structure.
AB  - A method is proposed that finds enriched pathways relevant to a studied condition
      using the measured molecular data and also the structural information of the
      pathway viewed as a network of nodes and edges. Tests are performed using
      simulated data and genomic data sets and the method is compared to two existing
      approaches. The analysis provided demonstrates the method proposed is very
      competitive with the current approaches and also provides biologically relevant
      results.

PMID- 19393086
TI  - Microbial co-habitation and lateral gene transfer: what transposases can tell us.
AB  - BACKGROUND: Determining the habitat range for various microbes is not a simple,
      straightforward matter, as habitats interlace, microbes move between habitats,
      and microbial communities change over time. In this study, we explore an approach
      using the history of lateral gene transfer recorded in microbial genomes to begin
      to answer two key questions: where have you been and who have you been with?
      RESULTS: All currently sequenced microbial genomes were surveyed to identify
      pairs of taxa that share a transposase that is likely to have been acquired
      through lateral gene transfer. A microbial interaction network including almost
      800 organisms was then derived from these connections. Although the majority of
      the connections are between closely related organisms with the same or
      overlapping habitat assignments, numerous examples were found of cross-habitat
      and cross-phylum connections. CONCLUSIONS: We present a large-scale study of the
      distributions of transposases across phylogeny and habitat, and find a
      significant correlation between habitat and transposase connections. We observed
      cases where phylogenetic boundaries are traversed, especially when organisms
      share habitats; this suggests that the potential exists for genetic material to
      move laterally between diverse groups via bridging connections. The results
      presented here also suggest that the complex dynamics of microbial ecology may be
      traceable in the microbial genomes.

PMID- 19393087
TI  - Implementation of population screening for colorectal cancer by repeated fecal
      occult blood test in the Netherlands.
AB  - BACKGROUND: Colorectal cancer (CRC) is the third most prevalent type of cancer in
      the world. Its prognosis is closely related to the disease stage at the time of
      diagnosis. Early detection of symptomless CRC or precursor lesions through
      population screening could reduce CRC mortality. However, screening programs are
      only effective if enough people are willing to participate. This study aims to
      asses the uptake of a second round of fecal occult blood test (FOBt) based
      screening and to explore factors that could potentially increase this uptake.
      METHODS AND DESIGN: Two years after the first screening round, 10.000 average
      risk persons, aged 50 to 75, will again receive an invitation to participate in
      immunohistochemical FOBt (iFOBt) based screening. Eligible persons will be
      recruited through a city population database. Invitees will be randomized to
      receive either an iFOBt with a faeces collection paper or an iFOBt without a
      collection paper. The iFOBts will be analyzed in a specialized laboratory at the
      Academic Medical Centre. Positive iFOBts will be followed by a consultation at
      our outpatient clinic and, in the absence of contra-indications and after
      informed consent, by a colonoscopy. The primary outcome measure is the
      participation rate. Secondary outcome measures are the effect of the addition of
      a collection paper on the participation rate, reasons for participation and non
      participation, measures of informed choice and psychological consequences of
      screening and measures of psychological and physical burden associated with the
      iFOBt and the colonoscopy. Another secondary outcome measure is the diagnostic
      yield of the program. DISCUSSION: In order to implement population screening for
      colorectal cancer in the Netherlands, information is needed on the uptake of
      repeated rounds of FOBt-based screening and on factors that could potentially
      increase this uptake in the future since effectiveness of such a program depends
      on the willingness of persons to participate. This study will provide information
      on the actual uptake and perception of a second round of iFOBt-based screening.
      The results of this study will contribute to the future implementation of a
      national colorectal screening program in the Netherlands. TRIAL REGISTRATION:
      Dutch Trial register: NTR1327.

PMID- 19393088
TI  - Interaction of hookworm 14-3-3 with the forkhead transcription factor DAF-16
      requires intact Akt phosphorylation sites.
AB  - BACKGROUND: Third-stage infective larvae (L3) of hookworms are in an obligatory
      state of developmental arrest that ends upon entering the definitive host, where
      they receive a signal that re-activates development. Recovery from the
      developmentally arrested dauer stage of Caenorhabditis elegans is analogous to
      the resumption of development during hookworm infection. Insulin-like signaling
      (ILS) mediates recovery from arrest in C. elegans and activation of hookworm
      dauer L3. In C. elegans, phosphorylation of the forkhead transcription factor DAF
      16 in response to ILS creates binding cites for the 14-3-3 protein Ce-FTT-2,
      which translocates DAF-16 out of the nucleus, resulting in resumption of
      reproductive development. RESULTS: To determine if hookworm 14-3-3 proteins play
      a similar role in L3 activation, hookworm FTT-2 was identified and tested for its
      ability to interact with A. caninum DAF-16 in vitro. The Ac-FTT-2 amino acid
      sequence was 91% identical to the Ce-FTT-2, and was most closely related to FTT-2
      from other nematodes. Ac-FTT-2 was expressed in HEK 293T cells, and was
      recognized by an antibody against human 14-3-3beta isoform. Reciprocal co
      immunoprecipitations using anti-epitope tag antibodies indicated that Ac-FTT-2
      interacts with Ac-DAF-16 when co-expressed in serum-stimulated HEK 293T cells.
      This interaction requires intact Akt consensus phosphorylation sites at serine107
      and threonine312, but not serine381. Ac-FTT-2 was undetectable by Western blot in
      excretory/secretory products from serum-stimulated (activated) L3 or adult A.
      caninum. CONCLUSION: The results indicate that Ac-FTT-2 interacts with DAF-16 in
      a phosphorylation-site dependent manner, and suggests that Ac-FTT-2 mediates
      activation of L3 by binding Ac-DAF-16 during hookworm infection.

PMID- 19393091
TI  - Working in disadvantaged communities: What additional competencies do we need?
AB  - BACKGROUND: Residents of socioeconomically disadvantaged locations are more
      likely to have poor health than residents of socioeconomically advantaged
      locations and this has been comprehensively mapped in Australian cities. These
      inequalities present a challenge for the public health workers based in or
      responsible for improving the health of people living in disadvantaged
      localities. The purpose of this study was to develop a generic workforce needs
      assessment tool and to use it to identify the competencies needed by the public
      health workforce to work effectively in disadvantaged communities. METHODS: A two
      step mixed method process was used to identify the workforce needs. In step 1 a
      generic workforce needs assessment tool was developed and applied in three NSW
      Area Health Services using focus groups, key stakeholder interviews and a staff
      survey. In step 2 the findings of this needs assessment process were mapped
      against the existing National Health Training Package (HLT07) competencies, gaps
      were identified, additional competencies described and modules of training
      developed to fill identified gaps. RESULTS: There was a high level of agreement
      among the AHS staff on the nature of the problems to be addressed but less
      confidence indentifying the work to be done. Processes for needs assessments,
      community consultations and adapting mainstream programs to local needs were
      frequently mentioned as points of intervention. Recruiting and retaining
      experienced staff to work in these communities and ensuring their safety were
      major concerns. Workforce skill development needs were seen in two ways: higher
      order planning/epidemiological skills and more effective working relationships
      with communities and other sectors. Organisational barriers to effective practice
      were high levels of annual compulsory training, balancing state and national
      priorities with local needs and giving equal attention to the population groups
      that are easy to reach and to those that are difficult to engage. A number of
      additional competency areas were identified and three training modules developed.
      CONCLUSION: The generic workforce needs assessment tool was easy to use and
      interpret. It appears that the public health workforce involved in this study has
      a high level of understanding of the relationship between the social determinants
      and health. However there is a skill gap in identifying and undertaking effective
      intervention.

PMID- 19393090
TI  - Efficient CPP-mediated Cre protein delivery to developing and adult CNS tissues.
AB  - BACKGROUND: Understanding and manipulating gene function in physiological
      conditions is a major objective for both fundamental and applied research. In
      contrast to other experimental settings, which use either purely genetic or gene
      delivery (viral or non-viral) strategies, we report here a strategy based on
      direct protein delivery to central nervous system (CNS) tissues. We fused Cre
      recombinase with cell-penetrating peptides and analyzed the intracellular
      biological activity of the resulting chimerical proteins when delivered into
      cells endowed with Cre-mediated reporter gene expression. RESULTS: We show that
      active Cre enzymatic conjugates are readily internalized and exert their
      enzymatic activity in the nucleus of adherent cultured cells. We then evaluated
      this strategy in organotypic cultures of neural tissue explants derived from
      reporter mice carrying reporter "floxed" alleles. The efficacy of two protocols
      was compared on explants, either by direct addition of an overlying drop of
      protein conjugate or by implantation of conjugate-coated beads. In both cases,
      delivery of Cre recombinase resulted in genomic recombination that, with the bead
      protocol, was restricted to discrete areas of embryonic and adult neural tissues.
      Furthermore, delivery to adult brain tissue resulted in the transduction of
      mature postmitotic populations of neurons. CONCLUSION: We provide tools for the
      spatially restricted genetic modification of cells in explant culture. This
      strategy allows to study lineage, migration, differentiation and death of neural
      cells. As a proof-of-concept applied to CNS tissue, direct delivery of Cre
      recombinase enabled the selective elimination of an interneuron subpopulation of
      the spinal cord, thereby providing a model to study early events of
      neurodegenerative processes. Thus our work opens new perspectives for both
      fundamental and applied cell targeting protocols using proteic cargoes which need
      to retain full bioactivity upon internalisation, as illustrated here with the
      oligomeric Cre recombinase.

PMID- 19393089
TI  - Cardiovascular magnetic resonance parameters of atherosclerotic plaque burden
      improve discrimination of prior major adverse cardiovascular events.
AB  - AIMS: Patients with prior major cardiovascular or cerebrovascular events (MACE)
      are more likely to have future recurrent events independent of traditional
      cardiovascular disease risk factors. The purpose of this study was to determine
      if patients with traditional risk factors and prior MACE had increased
      cardiovascular magnetic resonance (CMR) plaque burden measures compared to
      patients with risk factors but no prior events. METHODS AND RESULTS: Black blood
      carotid and thoracic aorta images were obtained from 195 patients using a rapid
      extended coverage turbo spin echo sequence. CMR measures of plaque burden were
      obtained by tracing lumen and outer vessel wall contours. Patients with prior
      MACE had significantly higher MR plaque burden (wall thickness, wall area and
      normalized wall index) in carotids and thoracic aorta compared to those without
      prior MACE (Wall thickness carotids: 1.03 +/- 0.03 vs. 0.93+/- 0.03, p = 0.001;
      SD wall thickness carotids: 0.137 +/- 0.0008 vs. 0.102 +/- 0.0004, p < 0.001;
      wall thickness aorta: 1.63 +/- 0.10 vs. 1.50 +/- 0.04, p = 0.009; SD wall
      thickness aorta: 0.186 +/- 0.035 vs. 0.139 +/- 0.012, p = 0.009 respectively).
      Plaque burden (wall thickness) and plaque eccentricity (standard deviation of
      wall thickness) of carotid arteries were associated with prior MACE after
      adjustment for age, sex, and traditional risk factors. Area under ROC curve (AUC)
      for discriminating prior MACE improved by adding plaque eccentricity to models
      incorporating age, sex, and traditional CVD risk factors as model inputs (AUC =
      0.79, p = 0.05). CONCLUSION: A greater plaque burden and plaque eccentricity is
      prevalent among patients with prior MACE.

PMID- 19393092
TI  - A novel promoter controls Cyp19a1 gene expression in mouse adipose tissue.
AB  - BACKGROUND: Aromatase, the key enzyme in estrogen biosynthesis, is encoded by the
      Cyp19a1 gene. Thus far, 3 unique untranslated first exons associated with
      distinct promoters in the mouse Cyp19a1 gene have been described (brain, ovary,
      and testis-specific). It remains unknown whether aromatase is expressed in other
      mouse tissues via novel and tissue-specific promoters. METHODS: Real-time PCR was
      used to examine the aromatase expression levels in various C57BL/6 mouse tissues.
      5'-rapid amplification of cDNA ends (5'-RACE) was used to determine the
      transcriptional start sites of Cyp19a1 transcripts. Promoter activity was
      measured using serial deletion mutants of DNA fused to the luciferase reporter
      gene. Primary mouse adipose fibroblasts were isolated and cultured from 16-week
      old mouse gonadal fat pads. RESULTS: We systematically analyzed Cyp19a1
      expression in a large number of mouse tissues, and demonstrated for the first
      time that aromatase was expressed in the male but not female gonadal fat pad.
      Subcutaneous and brown adipose tissue did not contain detectable Cyp19a1 mRNA. We
      used 5'-RACE to clone a novel gonadal fat-specific untranslated first exon, which
      is spliced onto a common junction 15 bp upstream of the translation start site.
      This adipose-specific first exon was mapped to approximately 75 kb upstream of
      the translation start site. Transfection of luciferase reporter gene plasmids
      containing the promoter region upstream of the adipose-specific first exon into
      murine 3T3-L1 adipose fibroblasts demonstrated significant basal promoter
      activity conferred primarily by the sequence located at -343/-1 bp. Dexamethasone
      significantly induced activity of this adipose-specific promoter region. Adipose
      specific Cyp19a1 mRNA was expressed in primary mouse adipose fibroblasts and
      significantly induced by dexamethasone alone or serum plus dexamethasone.
      CONCLUSION: Taken together, this research identified a novel, adipose-specific
      first exon of Cyp19a1 and its hormonally regulated promoter region in male murine
      gonadal fat. These results expand the known 5'-regulatory region of the murine
      Cyp19a1 gene to 75 kb upstream of the translation start site. Cyp19a1 expression
      in mouse adipose tissue may play an important role in reproductive biology and
      lipid metabolism.

PMID- 19393093
TI  - Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into
      influenza whole virus vaccines boosts immunogenicity and protection against
      lethal challenge.
AB  - BACKGROUND: Influenza epidemics continue to cause morbidity and mortality within
      the human population despite widespread vaccination efforts. This, along with the
      ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a
      much improved, more sophisticated influenza vaccine. We have developed an in
      vitro model system for producing a membrane-bound Cytokine-bearing Influenza
      Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and
      adaptive immunity and it is our goal to utilize the properties of individual
      cytokines and other immunomodulatory proteins to create a more immunogenic
      vaccine. RESULTS: We have evaluated the immunogenicity of inactivated cytokine
      bearing influenza vaccines using a mouse model of lethal influenza virus
      challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with
      mouse-derived cytokines (GM-CSF, IL-2 and IL-4) fused to the membrane-anchoring
      domain of the viral hemagglutinin. Influenza virus replication in these cell
      lines resulted in the uptake of the bioactive membrane-bound cytokines during
      virus budding and release. In vivo efficacy studies revealed that a single low
      dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against
      lethal influenza challenge in a mouse model and provides a more balanced Th1/Th2
      humoral immune response, similar to live virus infections. CONCLUSION: We have
      validated the protective efficacy of CYT-IVACs in a mammalian model of influenza
      virus infection. This technology has broad applications in current influenza
      virus vaccine development and may prove particularly useful in boosting immune
      responses in the elderly, where current vaccines are minimally effective.

PMID- 19393094
TI  - Resource heterogeneity and foraging behaviour of cattle across spatial scales.
AB  - BACKGROUND: Understanding the mechanisms that influence grazing selectivity in
      patchy environments is vital to promote sustainable production and conservation
      of cultivated and natural grasslands. To better understand how patch size and
      spatial dynamics influence selectivity in cattle, we examined grazing selectivity
      under 9 different treatments by offering alfalfa and fescue in patches of 3 sizes
      spaced with 1, 4, and 8 m between patches along an alley. We hypothesized that
      (1) selectivity is driven by preference for the forage species that maximizes
      forage intake over feeding scales ranging from single bites to patches along
      grazing paths, (2) that increasing patch size enhances selectivity for the
      preferred species, and that (3) increasing distances between patches restricts
      selectivity because of the aggregation of scale-specific behaviours across
      foraging scales. RESULTS: Cows preferred and selected alfalfa, the species that
      yielded greater short-term intake rates (P < 0.0001) and greater daily intake
      potential. Selectivity was not affected by patch arrangement, but it was scale
      dependent. Selectivity tended to emerge at the scale of feeding stations and
      became strongly significant at the bite scale, because of differences in bite
      mass between plant species. Greater distance between patches resulted in longer
      patch residence time and faster speed of travel but lower overall intake rate,
      consistent with maximization of intake rate. Larger patches resulted in greater
      residence time and higher intake rate. CONCLUSION: We conclude that patch size
      and spacing affect components of intake rate and, to a lesser extent, the
      selectivity of livestock at lower hierarchies of the grazing process,
      particularly by enticing livestock to make more even use of the available species
      as patches are spaced further apart. Thus, modifications in the spatial pattern
      of plant patches along with reductions in the temporal and spatial allocation of
      grazing may offer opportunities to improve uniformity of grazing by livestock and
      help sustain biodiversity and stability of plant communities.

PMID- 19393095
TI  - Needle guide in shoulder arthroscopy - a technique.
AB  - Distension of joint with fluid is often used to facilitate insertion of
      arthroscope. This may prove difficult at times in the shoulder joint, as unlike
      the knee, it is deeply situated, making extravasation of fluid outside the
      capsule, a common occurrence. This is especially true in very tight joints and is
      often a problem for beginners. We describe here a very effective and simple
      technique where a needle is used to distend the shoulder before the insertion of
      the arthroscope.

PMID- 19393096
TI  - A four-column theory for the origin of the genetic code: tracing the evolutionary
      pathways that gave rise to an optimized code.
AB  - BACKGROUND: The arrangement of the amino acids in the genetic code is such that
      neighbouring codons are assigned to amino acids with similar physical properties.
      Hence, the effects of translational error are minimized with respect to randomly
      reshuffled codes. Further inspection reveals that it is amino acids in the same
      column of the code (i.e. same second base) that are similar, whereas those in the
      same row show no particular similarity. We propose a 'four-column' theory for the
      origin of the code that explains how the action of selection during the build-up
      of the code leads to a final code that has the observed properties. RESULTS: The
      theory makes the following propositions. (i) The earliest amino acids in the code
      were those that are easiest to synthesize non-biologically, namely Gly, Ala, Asp,
      Glu and Val. (ii) These amino acids are assigned to codons with G at first
      position. Therefore the first code may have used only these codons. (iii) The
      code rapidly developed into a four-column code where all codons in the same
      column coded for the same amino acid: NUN = Val, NCN = Ala, NAN = Asp and/or Glu,
      and NGN = Gly. (iv) Later amino acids were added sequentially to the code by a
      process of subdivision of codon blocks in which a subset of the codons assigned
      to an early amino acid were reassigned to a later amino acid. (v) Later amino
      acids were added into positions formerly occupied by amino acids with similar
      properties because this can occur with minimal disruption to the proteins already
      encoded by the earlier code. As a result, the properties of the amino acids in
      the final code retain a four-column pattern that is a relic of the earliest
      stages of code evolution. CONCLUSION: The driving force during this process is
      not the minimization of translational error, but positive selection for the
      increased diversity and functionality of the proteins that can be made with a
      larger amino acid alphabet. Nevertheless, the code that results is one in which
      translational error is minimized. We define a cost function with which we can
      compare the fitness of codes with varying numbers of amino acids, and a barrier
      function, which measures the change in cost immediately after addition of a new
      amino acid. We show that the barrier is positive if an amino acid is added into a
      column with dissimilar properties, but negative if an amino acid is added into a
      column with similar physical properties. Thus, natural selection favours the
      assignment of amino acids to the positions that they occupy in the final code.

PMID- 19393098
TI  - A resting box for outdoor sampling of adult Anopheles arabiensis in rice
      irrigation schemes of lower Moshi, northern Tanzania.
AB  - BACKGROUND: Malaria vector sampling is the best method for understanding the
      vector dynamics and infectivity; thus, disease transmission seasonality can be
      established. There is a need to protecting humans involved in the sampling of
      disease vectors during surveillance or in control programmes. In this study,
      human landing catch, two cow odour baited resting boxes and an unbaited resting
      box were evaluated as vector sampling tools in an area with a high proportion of
      Anopheles arabiensis, as the major malaria vector. METHODS: Three resting boxes
      were evaluated against human landing catch. Two were baited with cow odour, while
      the third was unbaited. The inner parts of the boxes were covered with black
      cloth materials. Experiments were arranged in latin-square design. Boxes were set
      in the evening and left undisturbed; mosquitoes were collected at 06:00 am the
      next morning, while human landing catch was done overnight. RESULTS: A total of
      9,558 An. arabiensis mosquitoes were collected. 17.5% (N = 1668) were collected
      in resting box baited with cow body odour, 42.5% (N = 4060) in resting box baited
      with cow urine, 15.1% (N = 1444) in unbaited resting box and 24.9% (N = 2386)
      were collected by human landing catch technique. In analysis, the house positions
      had no effect on the density of mosquitoes caught (DF = 3, F = 0.753, P = 0.387);
      the sampling technique had significant impact on the caught mosquitoes densities
      (DF = 3, F 37. 944, P < 0.001). CONCLUSION: Odour-baited resting boxes have shown
      the possibility of replacing the existing traditional method (human landing
      catch) for sampling malaria vectors in areas with a high proportion of An.
      arabiensis as malaria vectors. Further evaluations of fermented urine and
      longevity of the urine odour still need to be investigated.

PMID- 19393097
TI  - PrognoScan: a new database for meta-analysis of the prognostic value of genes.
AB  - BACKGROUND: In cancer research, the association between a gene and clinical
      outcome suggests the underlying etiology of the disease and consequently can
      motivate further studies. The recent availability of published cancer microarray
      datasets with clinical annotation provides the opportunity for linking gene
      expression to prognosis. However, the data are not easy to access and analyze
      without an effective analysis platform. DESCRIPTION: To take advantage of public
      resources in full, a database named "PrognoScan" has been developed. This is 1) a
      large collection of publicly available cancer microarray datasets with clinical
      annotation, as well as 2) a tool for assessing the biological relationship
      between gene expression and prognosis. PrognoScan employs the minimum P-value
      approach for grouping patients for survival analysis that finds the optimal
      cutpoint in continuous gene expression measurement without prior biological
      knowledge or assumption and, as a result, enables systematic meta-analysis of
      multiple datasets. CONCLUSION: PrognoScan provides a powerful platform for
      evaluating potential tumor markers and therapeutic targets and would accelerate
      cancer research. The database is publicly accessible at
      http://gibk21.bse.kyutech.ac.jp/PrognoScan/index.html.

PMID- 19393099
TI  - FlyPhy: a phylogenomic analysis platform for Drosophila genes and gene families.
AB  - BACKGROUND: The availability of 12 fully sequenced Drosophila species genomes
      provides an excellent opportunity to explore the evolutionary mechanism,
      structure and function of gene families in Drosophila. Currently, several
      important resources, such as FlyBase, FlyMine and DroSpeGe, have been devoted to
      integrating genetic, genomic, and functional data of Drosophila into a well
      organized form. However, all of these resources are gene-centric and lack the
      information of the gene families in Drosophila. DESCRIPTION: FlyPhy is a
      comprehensive phylogenomic analysis platform devoted to analyzing the genes and
      gene families in Drosophila. Genes were classified into families using a graph
      based Markov Clustering algorithm and extensively annotated by a number of
      bioinformatic tools, such as basic sequence features, functional category, gene
      ontology terms, domain organization and sequence homolog to other databases.
      FlyPhy provides a simple and user-friendly web interface to allow users to browse
      and retrieve the information at multiple levels. An outstanding feature of the
      FlyPhy is that all the retrieved results can be added to a workset for further
      data manipulation. For the data stored in the workset, multiple sequence
      alignment, phylogenetic tree construction and visualization can be easily
      performed to investigate the sequence variation of each given family and to
      explore its evolutionary mechanism. CONCLUSION: With the above functionalities,
      FlyPhy will be a useful resource and convenient platform for the Drosophila
      research community. The FlyPhy is available at http://bioinformatics.zj.cn/fly/ .

PMID- 19393100
TI  - Influencing factors and clinical significance of the metastatic lymph nodes ratio
      in gastric adenocarcinoma.
AB  - BACKGROUND: To investigate influencing factors of the metastatic lymph nodes
      ratio (MLR) and whether it is related to survival in patients with gastric
      adenocarcinoma. METHODS: We retrospectively evaluated the clinical features of
      121 patients with gastric adenocarcinoma enrolled in our hospital between 2000
      and 2007. The receiver operating characteristic (ROC) curve was used to determine
      the cutoff of the MLR, and CK20 immunohistochemical staining was used to detect
      micrometastasis of the lymph nodes. RESULTS: The areas under the ROC curve of MLR
      used to predict the death of 3-year and 5-year postoperative patients were 0.826
      +/- 0.053 and 0.896 +/- 0.046. Thus MLR = 30.95% and MLR = 3.15% were designated
      as cutoffs. The MLR was then classified into three groups: MLR1 (MLR<3.15%);
      MLR2(3.15% < or = MLR < or = 30.95%); and MLR3 (MLR>30.95%). We found that
      patients with a higher MLR demonstrated a much poorer survival period after
      radical operation than those patients with a lower MLR (P = 0.000). The COX model
      showed that MLR was an independent prognostic factor (P = 0.000). The MLR could
      also discriminate between subsets of patients with different 5-year survival
      periods within the same N stage (P < 0.05). The MLR has been shown to be 34.7%
      (242/697) by HE staining and 43.5% (303/697) by CK staining (P = 0.001). The
      clinicopathological characteristics of lymph vessel invasion and the depth of
      invasion could significantly affect the MLR. CONCLUSION: MLR is an independent
      prognostic factor in gastric cancer. The combined ROC curve with MLR is an
      effective strategy to produce a curve to predict the 3-year and 5-year survival
      rates.

PMID- 19393102
TI  - Respiratory care and cystic fibrosis. Foreward.

PMID- 19393101
TI  - Simulation-based model checking approach to cell fate specification during
      Caenorhabditis elegans vulval development by hybrid functional Petri net with
      extension.
AB  - BACKGROUND: Model checking approaches were applied to biological pathway
      validations around 2003. Recently, Fisher et al. have proved the importance of
      model checking approach by inferring new regulation of signaling crosstalk in C.
      elegans and confirming the regulation with biological experiments. They took a
      discrete and state-based approach to explore all possible states of the system
      underlying vulval precursor cell (VPC) fate specification for desired properties.
      However, since both discrete and continuous features appear to be an
      indispensable part of biological processes, it is more appropriate to use
      quantitative models to capture the dynamics of biological systems. Our key
      motivation of this paper is to establish a quantitative methodology to model and
      analyze in silico models incorporating the use of model checking approach.
      RESULTS: A novel method of modeling and simulating biological systems with the
      use of model checking approach is proposed based on hybrid functional Petri net
      with extension (HFPNe) as the framework dealing with both discrete and continuous
      events. Firstly, we construct a quantitative VPC fate model with 1761 components
      by using HFPNe. Secondly, we employ two major biological fate determination rules
      - Rule I and Rule II - to VPC fate model. We then conduct 10,000 simulations for
      each of 48 sets of different genotypes, investigate variations of cell fate
      patterns under each genotype, and validate the two rules by comparing three
      simulation targets consisting of fate patterns obtained from in silico and in
      vivo experiments. In particular, an evaluation was successfully done by using our
      VPC fate model to investigate one target derived from biological experiments
      involving hybrid lineage observations. However, the understandings of hybrid
      lineages are hard to make on a discrete model because the hybrid lineage occurs
      when the system comes close to certain thresholds as discussed by Sternberg and
      Horvitz in 1986. Our simulation results suggest that: Rule I that cannot be
      applied with qualitative based model checking, is more reasonable than Rule II
      owing to the high coverage of predicted fate patterns (except for the genotype of
      lin-15ko; lin-12ko double mutants). More insights are also suggested. CONCLUSION:
      The quantitative simulation-based model checking approach is a useful means to
      provide us valuable biological insights and better understandings of biological
      systems and observation data that may be hard to capture with the qualitative
      one.

PMID- 19393103
TI  - Cystic fibrosis and the respiratory therapist: a 50-year perspective.
AB  - The role of the respiratory therapist in the care of patients with cystic
      fibrosis has expanded throughout the years. As key members of the
      multidisciplinary team, respiratory therapists actively participate in the
      medical management of patients with cystic fibrosis along the continuum of care,
      from acute in-patient stays to the out-patient clinic and/or home setting.
      Through their involvement in diagnostic testing, administering therapy, or direct
      bedside care, patient and caregiver education, and disease management,
      respiratory therapists strive to preserve lung function, maintain overall health,
      and improve the patient's quality of life.

PMID- 19393104
TI  - Cystic fibrosis: pathogenesis and future treatment strategies.
AB  - Since the detection of the underlying gene defect, our knowledge of how the
      genetic mutations in cystic fibrosis cause lung disease has increased
      substantially, but we still lack a complete understanding of some of the pieces
      in the puzzle. Nevertheless, the information gained has led to new therapeutic
      approaches that address key factors of cystic fibrosis pathophysiology. Past
      therapeutic successes were largely based on targeting the consequences of the
      cystic fibrosis transmembrane regulator dysfunction, such as phlegm retention,
      infection, and inflammation, but new therapies may be able to address the
      underlying abnormality rather than its downstream effects. The efficacy of these
      treatments still needs to be established, but early studies look promising for
      several compounds. This review summarizes our current understanding of the
      pathophysiology and treatment of cystic fibrosis lung disease.

PMID- 19393105
TI  - Monitoring respiratory disease severity in cystic fibrosis.
AB  - Measurements of disease severity provide a guide for the physician to tailor
      therapies, for the patient and family to gauge progress, and are required for
      clinical trials. For many respiratory diseases, including cystic fibrosis,
      sensitive, noninvasive measurements are few, and some of those that are available
      are applicable only to certain subgroups of patients or lack sufficient
      sensitivity. We discuss currently available measurements in 4 groups: physiology,
      infection, inflammation, and radiology. For each group we highlight strengths and
      weaknesses, ask how we could improve upon these, and provide details of
      alternative methods.

PMID- 19393106
TI  - Pulmonary complications of cystic fibrosis.
AB  - Earlier diagnosis, treatment of exacerbations, and the use of long-term therapies
      have all improved the lifespan of patients with cystic fibrosis (CF). However,
      the natural history of CF airways disease remains one of worsening bronchiectasis
      and obstructive airways impairment. The progression of airways disease leads to
      eventual respiratory failure, but some will suffer other acute respiratory
      complications that require intervention, including pneumothorax, massive
      hemoptysis, and respiratory failure. Here I discuss the pathophysiology of these
      complications and the patient-related and treatment-related factors associated
      with their occurrence. Knowledge of these associations may play great importance
      in treatment decisions regarding the care of the patient and the respiratory
      therapist should be aware of the implications. Since disease severity is
      associated with all 3 conditions, aggressive treatment of the underlying
      condition is imperative, which includes the performance of airway-clearance
      therapies. Though some might argue that airway-clearance therapies might
      aggravate or even precipitate complications such as hemoptysis and pneumothorax,
      others will defend that there are airway-clearance therapies that might be safely
      performed. Aerosolized medications such as dornase alfa and tobramycin have been
      associated with a lower incidence of massive hemoptysis and are recommended
      therapies for patients with advanced airways disease, yet they are also
      associated with a higher incidence of pneumothorax, which suggests careful
      assessment of their potential bronchospastic effect in patients with advanced
      airways disease. The respiratory therapist also plays a key role in the care of
      the patient with respiratory failure. Here is also discussed the role of
      ventilatory support and airway-clearance therapies in the patient with advanced
      stage disease. Now, more than ever, the patient needs caregivers with the
      knowledge and sensitivity to provide appropriate palliative care.

PMID- 19393107
TI  - Bugs, biofilms, and resistance in cystic fibrosis.
AB  - Bacteria infect the respiratory tract early in the course of cystic fibrosis
      disease, often fail to be eradicated, and together with an aggressive host
      inflammatory response, are thought to be key players in the irreversible airway
      damage from which most patients ultimately die. Although incompletely understood,
      certain aspects of the cystic fibrosis airway itself appear to favor the
      development of chronic modes of survival, in particular biofilm formation; this
      and the development of antibiotic resistance following exposure to multiple
      antibiotic courses lead to chronic, persistent infection. In addition to the
      common cystic fibrosis pathogens, such as Staphylococcus aureus, Haemophilus
      influenzae, and Pseudomonas aeruginosa, several newer species are becoming more
      common. Furthermore, new molecular techniques have led to the identification of
      multiple different organisms within respiratory secretions, many of which are not
      cultured with conventional tools. Future work should aim to develop clinically
      applicable methods to identify these and to determine which have the potential to
      impact pulmonary health. We outline the basic tenets of infection control and
      treatment.

PMID- 19393108
TI  - Infection control in cystic fibrosis: cohorting, cross-contamination, and the
      respiratory therapist.
AB  - Cystic fibrosis (CF) is a complex genetic disease characterized by lung
      infections that lead to early morbidity and death. Pathogens that commonly infect
      the lungs of patients with CF include Staphylococcus aureus, Haemophilus
      influenzae, Pseudomonas aeruginosa, and Burkholderia cepacia. Aggressively
      treating pulmonary infection with antibiotics has contributed to improved
      survival in patients with CF but has also promoted multiple-drug-resistant
      bacteria. Other complexities include the ability of bacteria to form biofilms,
      which makes them more resistant to antibiotics, and emerging pathogens in CF, of
      which the clinical importance is not yet clear. Increasing evidence of patient-to
      patient transmission of CF pathogens led the Cystic Fibrosis Foundation to
      produce evidence-based infection-control recommendations, which stress 4
      principles: standard precautions, transmission-based precautions, hand hygiene,
      and care of respiratory equipment. Respiratory therapists need to know and follow
      these infection-control recommendations. Cohorting patients infected with B.
      cepacia complex is one of several interventions successful at keeping the spread
      of this pathogen low, but cohorting patients who are infected/colonized with
      other microbes is controversial, the main argument of which is not being certain
      of a patient's present respiratory culture status at any given patient visit.

PMID- 19393109
TI  - Aerosol antibiotics in cystic fibrosis.
AB  - Chronic airways infection and inflammation is the greatest source of morbidity
      and mortality in cystic fibrosis (CF) patients. Many organisms can be found in
      the lower respiratory tract of CF patients, but infection with mucoid Pseudomonas
      aeruginosa is common, is associated with poorer outcomes, and is the main target
      for antimicrobial strategies in CF. Aerosol antibiotics achieve high local
      concentrations in the airways, reduce systemic toxicity, and have been used
      successfully for chronic suppressive treatment for established P. aeruginosa
      infections. Eradication of early P. aeruginosa airway infection has also been
      tried with aerosol antibiotics, though the ideal treatment strategy is still
      being investigated. There are several variables to consider when choosing an
      antibiotic formulation to develop for topical inhalation. Tobramycin solution for
      inhalation (TSI) is currently the only approved inhaled antibiotic in the United
      States. The time burden for patients to administer TSI by jet nebulizer is
      substantial, so efforts have focused on more efficient, faster delivery methods.
      Novel formulations of aerosol antibiotics are being studied for CF, including
      beta-lactams, fluoroquinolones and aminoglycosides. Phase-3 studies of aztreonam
      lysinate for inhalation delivered via a proprietary eFlow nebulizer showed
      improved outcomes and a short (< 3 min) delivery time. Liposome formulations are
      being studied as a way to penetrate mucoid biofilms and prolong the residence
      time of the antibiotic in the lungs. Light, porous, dry-powder formulations are
      also in clinical trials to reduce delivery time. These new formulations and
      delivery systems promise to expand our armamentarium against microbes while
      reducing the time burden for patients.

PMID- 19393110
TI  - Increased bioavailability of hesperetin-7-glucoside compared with hesperidin
      results in more efficient prevention of bone loss in adult ovariectomised rats.
AB  - Hesperidin (Hp), a citrus flavonoid predominantly found in oranges, shows bone
      sparing effects in ovariectomised (OVX) animals. In human subjects, the
      bioavailability of Hp can be improved by the removal of the rhamnose group to
      yield hesperetin-7-glucoside (H-7-glc). The aim of the present work was to test
      whether H-7-glc was more bioavailable and therefore more effective than Hp in the
      prevention of bone loss in the OVX rat. Adult 6-month-old female Wistar rats were
      sham operated or OVX, then pair fed for 90 d a casein-based diet supplemented or
      not with freeze-dried orange juice enriched with Hp or H-7-glc at two dose
      equivalents of the hesperetin aglycone (0.25 and 0.5 %). In the rats fed 0.5 %, a
      reduction in OVX-induced bone loss was observed regarding total bone mineral
      density (BMD):+7.0 % in OVX rats treated with Hp (HpOVX) and +6.6 % in OVX rats
      treated with H-7-glc (H-7-glcOVX) v. OVX controls (P < 0.05). In the rats fed
      0.25 % hesperetin equivalents, the H-7-glcOVX group showed a 6.6 % improvement in
      total femoral BMD v. the OVX controls (P < 0.05), whereas the Hp diet had no
      effect at this dose. The BMD of rats fed 0.25 % H-7-glc was equal to that of
      those given 0.5 % Hp, but was not further increased at 0.5 % H-7-glc. Plasma
      hesperetin levels and relative urinary excretion were significantly enhanced in
      the H-7-glc v. Hp groups, and the metabolite profile showed the absence of
      eriodictyol metabolites and increased levels of hesperetin sulphates. Taken
      together, improved bioavailability of H-7-glc may explain the more efficient bone
      protection of this compound.

PMID- 19393111
TI  - Ageing and vitamin D deficiency: effects on calcium homeostasis and
      considerations for vitamin D supplementation.
AB  - Vitamin D is a fat-soluble, seco-steroid hormone. In man, the vitamin D receptor
      is expressed in almost all tissues, enabling effects in multiple systems of the
      human body. These effects can be endocrine, paracrine and autocrine. The present
      review summarises the effects of ageing on the vitamin D endocrine system and on
      Ca homeostasis. Furthermore, consequences for vitamin D supplementation are
      discussed.

PMID- 19393112
TI  - Quantitative aspects of the metabolism of lignans in pigs fed fibre-enriched rye
      and wheat bread.
AB  - A diet rich in lignans has been suggested to be protective against a range of
      chronic diseases. The distribution and metabolic fate of lignans is, however,
      very poorly understood. We fed high-fibre wheat breads low in lignans (n 8) or
      high-fibre rye breads (n 9) rich in plant lignans to pigs for 58-67 d, and
      analysed the content of plant lignans and their metabolites in the diet, blood,
      bile, faeces, urine and selected tissues. Apparent faecal digestibility of
      dietary precursors was higher than of total (plant- and entero-) lignans due to
      conversion to enterolactone and enterodiol. The digestibility of lariciresinol
      and matairesinol was lower than that of the sum of plant lignans. This suggests
      that interconversion of plant lignans during digestion and enterohepatic
      circulation occur without complete conversion to enterolignans. The majority of
      lignans present in plasma and urine was in the form of enterolignans, but up to
      23 % in the plasma, and 11 % in the urine of the rye-fed pigs were in the form of
      plant lignans. There was a very high concentration of lignans in bile from the
      rye-fed pigs with as much as 77 % in the form of plant lignans. Lignans were
      detected in the tissue of colon, liver, breast and brain at a much higher level
      with rye than with wheat, but only in the form of enterolactone. The importance
      and implications of systemic exposure to plant lignans remain to be elucidated.

PMID- 19393113
TI  - Ruminal metabolism of flaxseed ( Linum usitatissimum) lignans to the mammalian
      lignan enterolactone and its concentration in ruminal fluid, plasma, urine and
      milk of dairy cows.
AB  - Secoisolariciresinol diglucoside is the main flax (Linum usitatissimum) lignan
      that is converted to the mammalian lignans enterodiol (ED) and enterolactone (EL)
      by gastrointestinal microbiota. The objectives of the present study were to
      investigate the role of ruminal microbiota and the effects of flax oil on in vivo
      metabolism of flax lignans and concentration of EL in biological fluids. Four
      rumen-cannulated dairy cows were used in a 4 x 4 Latin square design. There were
      four periods of 21 d each and four treatments utilising flax hulls (1800 g/d) and
      oil (400 g/d) supplements. The treatments were: (1) oil and hulls administered in
      the rumen and abomasal infusion of water; (2) oil and hulls administered in the
      abomasum; (3) oil infused in the abomasum and hulls placed in the rumen; (4) oil
      placed in the rumen and hulls administered in the abomasum. Samples were
      collected during the last week of each period and subjected to chemical analysis.
      The site of supplementation of oil and hulls had no effect on ruminal EL
      concentration. Supplementing flax oil in the rumen and the abomasum led to
      similar EL concentrations in urine, plasma and milk. Concentrations of EL were
      higher in the urine, plasma and milk of cows supplemented with hulls in the rumen
      than in those placed with hulls in the abomasum. The present study demonstrated
      that ruminal microbiota play an important role in the metabolism of flax lignans.

PMID- 19393114
TI  - Attenuation of proteolysis and muscle wasting by curcumin c3 complex in MAC16
      colon tumour-bearing mice.
AB  - Muscle wasting or cachexia is caused by accelerated muscle protein breakdown via
      the ubiquitin-proteasome complex. We investigated the effect of curcumin c3
      complex (curcumin c3) on attenuation of muscle proteolysis using in vitro and in
      vivo models. Our in vitro data indicate that curcumin c3 as low as 0.50 microg/ml
      was very effective in significantly inhibiting (30 %; P < 0.05) tyrosine release
      from human skeletal muscle cells, which reached a maximum level of inhibition of
      60 % (P < 0.05) at 2.5 microg/ml. Curcumin c3 at 2.5 microg/ml also inhibited
      chymotrypsin-like 20S proteasome activity in these cells by 25 % (P < 0.05). For
      in vivo studies, we induced progressive muscle wasting in mice by implanting the
      MAC16 colon tumour. The in vivo data indicate that low doses of curcumin c3 (100
      mg/kg body weight) was able to prevent weight loss in mice bearing MAC16 tumours
      whereas higher doses of curcumin c3 (250 mg/kg body weight) resulted in
      approximately 25 % (P < 0.05) weight gain as compared with the placebo-treated
      animals. Additionally, the effect of curcumin c3 on preventing and/or reversing
      cachexia was also evident by gains in the weight of the gastrocnemius muscle (30
      58 %; P < 0.05) and with the increased size of the muscle fibres (30-65 %; P <
      0.05). Furthermore, curcumin inhibited proteasome complex activity and variably
      reduced expression of muscle-specific ubiquitin ligases: atrogin-1/muscle atrophy
      F-box (MAFbx) and muscle RING finger 1 (MURF-1). In conclusion, oral curcumin c3
      results in the prevention and reversal of weight loss. The data imply that
      curcumin c3 may be an effective adjuvant therapy against cachexia.

PMID- 19393115
TI  - Dietary lipid level affects growth performance and nutrient utilisation of
      Senegalese sole ( Solea senegalensis) juveniles.
AB  - Over the last few years, several aspects of Senegalese sole (Solea senegalensis)
      culture have been developed and optimised but the dietary lipid level for optimal
      growth has never been determined. Hence, five isonitrogenous diets (56 % dietary
      protein) with increasing dietary lipid levels (4, 8, 12, 16 and 20 % DM) were fed
      to satiation to triplicate groups of twenty fish (mean initial weight 10 g).
      Fifteen tanks were randomly assigned one of the five diets. Feed was distributed
      using automatic feeders, and fish were fed over a 16-week period. At the end of
      the experiment the fish fed on diets containing the two lowest dietary lipid
      levels (4 and 8 %) showed a 3-fold body-weight increase with a significantly
      higher daily growth index than fish fed higher lipid levels (1.2 v. 0.8).
      Moreover, these fish displayed a significantly lower dry feed intake (12 g/kg per
      d) and feed conversion ratio (1.0) compared with fish fed higher lipids levels
      (16-19 g/kg per d; feed conversion ratio 2.0). Low dietary lipid levels ( < 12 %)
      significantly improved nutrient retention and gain and hence growth, without
      major effects on whole-body composition. Despite the slight alteration in n-3
      PUFA muscle content in the fish fed low-fat-diets, this fish fed low dietary
      lipid still remains a rich n-3 PUFA product and generally maintained its
      nutritional value. These results evidenced a low lipid tolerance of Senegalese
      sole juveniles and suggest a maximal dietary inclusion level of 8 % lipids for
      both optimal growth and nutrient utilisation without compromising flesh quality.

PMID- 19393116
TI  - High prevalence of Leptospira spp. in sewer rats (Rattus norvegicus).
AB  - Earlier studies on the ecology of leptospirosis in temperate regions focused
      mainly on free-ranging rats in rural areas. Here we report on the occurrence of
      Leptospira spp. in Rattus norvegicus living in sewers in a suburban area in
      Copenhagen, Denmark. In 2006-2007, about 30 rats were captured in sewers at each
      of six different locations. Rat kidneys were screened by PCR for pathogenic
      Leptospira spp. In one location no infected rats were found, whereas the
      prevalence in the remaining five locations ranged between 48% and 89%. Micro
      agglutination tests showed that serogroup Pomona, Sejroe, and Icterohaemorrhagiae
      were the most common. Infection was related to age with the highest prevalence
      observed for adult rats but there was no difference in infection rate between
      sexes, suggesting primarily environmental transmission. Since most reported rat
      problems in urban areas are related to sewer rats, the surprisingly high level of
      infection calls for an increased public health concern.

PMID- 19393117
TI  - Blastocystis: unravelling potential risk factors and clinical significance of a
      common but neglected parasite.
AB  - Two independent studies were conducted to describe symptoms and potential risk
      factors associated with Blastocystis infection. Isolates were subtyped by
      molecular analysis. In the NORMAT study (126 individuals randomly sampled from
      the general population) 24 (19%) were positive for Blastocystis. Blastocystis was
      associated with irritable bowel syndrome (P=0.04), contact with pigs (P<0.01) and
      poultry (P=0.03). In the Follow-up (FU) study (follow-up of 92 Blastocystis
      positive patients), reports on bloating were associated with subtype (ST) 2
      (P<0.01), and blood in stool to mixed subtype infection (P=0.06). ST1 was more
      common in FU individuals (32%) than in NORMAT individuals (8%), whereas single
      subtype infections due to ST3 or ST4 were seen in 63% of the NORMAT cases and 28%
      of the FU cases. Only FU individuals hosted ST7, and ST6/7 infections due to ST7
      or ST9 were characterized by multiple intestinal symptoms. The data indicate
      subtype-dependent differences in the clinical significance of Blastocystis.

PMID- 19393118
TI  - GIS-based spatial, temporal, and space-time analysis of haemorrhagic fever with
      renal syndrome.
AB  - We obtained a list of all reported cases of haemorrhagic fever with renal
      syndrome (HFRS) in Shenyang, China, during 1990-2003, and used GIS-based scan
      statistics to determine the distribution of HFRS cases and to identify key areas
      and periods for future risk-factor research. Spatial cluster analysis suggested
      three areas were at increased risk for HFRS. Temporal cluster analysis suggested
      one period was at increased risk for HFRS. Space-time cluster analysis suggested
      six areas from 1995 to 1996 and four areas from 1998 to 2003 were at increased
      risk for HFRS. We also discussed the likely reasons for these clusters. We
      conclude that GIS-based scan statistics may provide an opportunity to classify
      the epidemic situation of HFRS, and we can pursue future investigations to study
      the likely factors responsible for the increased disease risk based on the
      classification.

PMID- 19393119
TI  - Effect of recipient breed on delivery rate of cloned miniature pig.
AB  - The miniature pig is regarded as a better organ donor breed for
      xenotransplantation than other pig breeds because the size of their organs is
      similar to that of humans. To improve efficiency of cloned miniature pig
      production, we analysed the effect of breed difference between donor cells and
      embryo recipients on pregnancy rate and delivery rate. Cloned porcine embryos
      derived from domestic or miniature pig donor cells were transferred to domestic
      or miniature recipient pigs. Delivery rate was significantly higher when embryos
      reconstructed with miniature pig donor cells were transferred to miniature pig
      recipients as compared with that of embryos transferred to domestic pig
      recipients. However, pregnancy rates were similar between the two groups. The
      breed of donor cells, but not of embryo recipients, seems likely to affect litter
      size. From a 13 610 gene cDNA microarray, 1551 (11.7%) genes showed significantly
      different levels of expression between the fetuses of the two breeds. Vascular
      endothelial growth factor and c-kit ligand genes related to implantation and
      maintenance of pregnancy were significantly down-regulated in miniature pigs. In
      conclusion, the differential gene expression in fetuses interferes with proper
      fetal/maternal interactions, and results in late-stage pregnancy loss. Our
      results indicate that the miniature pig is the preferred embryo recipient breed
      than domestic pig for producing cloned miniature piglets.

PMID- 19393120
TI  - A retrospective model of oocyte competence: global mRNA and housekeeping
      transcripts are not associated with in vitro developmental outcome.
AB  - SummaryOocyte developmental competence depends on maternal stores that support
      development throughout a transcriptionally silent period during early
      embryogenesis. Previous attempts to investigate transcripts associated with
      oocyte competence have relied on prospective models, which are mostly based on
      morphological criteria. Using a retrospective model, we quantitatively compared
      mRNA among oocytes with different embryo development competence. A cytoplasm
      biopsy was removed from in vitro matured oocytes to perform comparative analysis
      of amounts of global polyadenylated (polyA) mRNA and housekeeping gene
      transcripts. After parthenogenetic activation of biopsied oocytes, presumptive
      zygotes were cultured individually in vitro and oocytes were classified according
      to embryo development: (i) blocked before the 8-cell stage; (ii) blocked between
      the 8-cell and morulae stages; or (iii) developed to the blastocyst stage. Sham
      manipulated controls confirmed that biopsies did not alter development outcome.
      Total polyA mRNA amounts correlate with oocyte diameter but not with the ability
      to develop to the 8-cell and blastocyst stages. The last was also confirmed by
      relative quantification of GAPDH, H2A and Hprt1 transcripts. In conclusion, we
      describe a novel retrospective model to identify putative markers of development
      competence in single oocytes and demonstrate that global mRNA amounts at the
      metaphase II stage do not correlate with embryo development in vitro.

PMID- 19393121
TI  - Nursing staff knowledge and attitudes towards deliberate self-harm in adults and
      adolescents in an inpatient setting.
AB  - BACKGROUND: This paper investigates the relationship between care staff
      perceptions' of self-harm behaviours presented by adult and adolescent inpatients
      and the emotional responses and helping behaviours of the staff. METHOD: Seventy
      six nursing staff participated, including qualified and unqualified staff, who
      worked in either adolescent or adult secure inpatient settings within a single
      organization. Participants completed vignette, knowledge, and attitudes
      questionnaires, related to working with patients who display deliberate self
      harm. RESULTS: Further support was found for attributional theories suggesting
      that views on deliberate self-harm are linked to propensity to help, and that
      emotional responses can be a mediating factor. Staff who reported feeling more
      negative about patients who self-harm reported more worry about working with this
      patient group. Unqualified nursing staff reported more negativity and worry than
      qualified staff. Neither gender nor length of work experience was found to be
      significant factors. CONCLUSIONS: These findings indicate that training and
      support should be aimed at helping nursing staff, particularly unqualified staff
      working in inpatient settings where self-harm is frequent, feel more positive and
      less concerned about working with patients who self-harm. Such needs of
      unqualified nursing staff have not been highlighted in previous research.

PMID- 19393122
TI  - Anterior cervical osteophytes resulting in severe dysphagia and aspiration: two
      case reports and literature review.
AB  - OBJECTIVE: We report two cases in which dysphagia and aspiration, caused by
      anterior cervical osteophytes, were so severe that surgical resection was
      performed. METHOD: Case reports and a review of the world literature concerning
      dysphagia caused by anterior cervical osteophytes, in regard to pathogenesis,
      diagnosis and treatment. RESULTS: Two patients, aged 71 and 70 years, had long
      standing, slowly progressive dysphagia and aspiration; one patient had recurrent
      episodes of aspiration pneumonia as a result. Both patients were diagnosed on
      videofluoroscopy with large bony anterior cervical osteophytes. Immediate relief
      of symptoms was obtained after resection of the osteophytes via an anterolateral,
      extrapharyngeal approach. Anterior cervical osteophytes are relatively common in
      the elderly, although not frequently diagnosed, and are mostly seen in cases of
      diffuse idiopathic skeletal hyperostosis. If therapy is indicated it is mainly
      conservative; resection is rarely needed. CONCLUSION: In patients with anterior
      cervical osteophytes, surgical treatment is indicated only for selected cases
      with large, bony osteophytes and severe symptoms.

PMID- 19393123
TI  - Management of paediatric sinonasal rhabdomyosarcoma.
AB  - BACKGROUND AND AIM: Rhabdomyosarcoma is the commonest malignant tumour of the
      nose and paranasal sinuses in the paediatric population. Due to its rarity and
      largely unknown biological behaviour, the treatment of this tumour is complex and
      controversial. We present the results of multimodality treatment of paediatric
      sinonasal rhabdomyosarcoma, and we explore the role of surgery in the management
      of this malignancy. METHODS: We retrospectively reviewed the records of 14
      patients (median age 7.5 years) with sinonasal rhabdomyosarcoma. Six patients
      underwent major surgery with post-operative chemoradiation. Eight patients
      received multi-agent chemotherapy and radiotherapy. The mean follow-up time was
      58 months (range seven to 276 months). RESULTS: The five-year overall survival
      rates for all patients and for the surgery group were 53.9 and 83.3 per cent,
      respectively. All patients with alveolar rhabdomyosarcoma had a poor prognosis,
      with a median survival time of 17 months. Intracranial extension and an age
      greater than 10 years were also associated with an unfavourable outcome. Non- or
      partial responders to initial chemoradiation died within a year of diagnosis.
      CONCLUSIONS: Management of paediatric rhabdomyosarcoma requires a combination of
      chemotherapy, radiotherapy and surgery. Primary chemoradiotherapy is the
      established treatment approach for advanced tumours. Early stage tumours with
      favourable histology can be treated successfully with radical surgery, provided
      that function and cosmetic appearance are preserved.

PMID- 19393124
TI  - A tale of two parasites: the comparative epidemiology of cryptosporidiosis and
      giardiasis.
AB  - New Zealand has a higher reported incidence of cryptosporidiosis and giardiasis
      than most other developed countries. This study aimed to describe and compare the
      epidemiology of these infections in New Zealand, to better understand their
      impact on public health and to gain insight into their probable modes of
      transmission. We analysed cryptosporidiosis and giardiasis notification data for
      a 10-year period (1997-2006). Highest rates for both diseases were in Europeans,
      children aged 0-5 years, and those living in low-deprivation areas.
      Cryptosporidiosis distribution was consistent with mainly farm animal (zoonotic)
      reservoirs. There was a dose-response relationship with increasing grades of
      rurality, marked spring seasonality, and positive correlation with farm animal
      density. Giardiasis distribution was consistent with predominantly human
      (anthroponotic) reservoirs, with an important contribution from overseas travel.
      Further research should focus on methods to reduce transmission of
      Cryptosporidium in rural areas and on reducing anthroponotic transmission of
      Giardia.

PMID- 19393125
TI  - A study on the mapping of quantitative trait loci in advanced populations derived
      from two inbred lines.
AB  - In genetic and biological studies, the F2 population is one of the most popular
      and commonly used experimental populations mainly because it can be readily
      produced and its genome structure possesses several niceties that allow for
      productive investigation. These niceties include the equivalence between the
      proportion of recombinants and recombination rates, the capability of providing a
      complete set of three genotypes for every locus and an analytically attractive
      first-order Markovian property. Recently, there has been growing interest in
      using the progeny populations from F2 (advanced populations) because their
      genomes can be managed to meet specific purposes or can be used to enhance
      investigative studies. These advanced populations include recombinant inbred
      populations, advanced intercrossed populations, intermated recombinant inbred
      populations and immortalized F2 populations. Due to an increased number of
      meiosis cycles, the genomes of these advanced populations no longer possess the
      Markovian property and are relatively more complicated and different from the F2
      genomes. Although issues related to quantitative trait locus (QTL) mapping using
      advanced populations have been well documented, still these advanced populations
      are often investigated in a manner similar to the way F2 populations are studied
      using a first-order Markovian assumption. Therefore, more efforts are needed to
      address the complexities of these advanced populations in more details. In this
      article, we attempt to tackle these issues by first modifying current methods
      developed under this Markovian assumption to propose an ad hoc method (the
      Markovian method) and explore its possible problems. We then consider the
      specific genome structures present in the advanced populations without invoking
      this assumption to propose a more adequate method (the non-Markovian method) for
      QTL mapping. Further, some QTL mapping properties related to the confounding
      problems that result from ignoring epistasis and to mapping closely linked QTL
      are derived and investigated across the different populations. Simulations show
      that the non-Markovian method outperforms the Markovian method, especially in the
      advanced populations subject to selfing. The results presented here may give some
      clues to the use of advanced populations for more powerful and precise QTL
      mapping.

PMID- 19393126
TI  - Molecular cloning and evolutionary analysis of the GJA1 (connexin43) gene from
      bats (Chiroptera).
AB  - Gap junction protein connexin43 (Cx43), encoded by the GJA1 gene, is the most
      abundant connexin in the cardiovascular system and was reported as a crucial
      factor maintaining cardiac electrical conduction, as well as having a very
      important function in facilitating the recycling of potassium ions from hair
      cells in the cochlea back into the cochlear endolymph during auditory
      transduction processes. In mammals, bats are the only taxon possessing powered
      flight, placing exceptional demand on many organismal processes. To meet the
      demands of flying, the hearts of bats show many specialties. Moreover, ultrasonic
      echolocation allows bat species to orientate and often detect and locate food in
      darkness. In this study, we cloned the full-length coding region of GJA1 gene
      from 12 different species of bats and obtained orthologous sequences from other
      mammals. We used the maximum likelihood method to analyse the evolution of GJA1
      gene in mammals and the lineage of bats. Our results showed this gene is much
      conserved in mammals, as well as in bats' lineage. Compared with other mammals,
      we found one private amino acid substitution shared by bats, which is located on
      the inner loop domain, as well as some species-specific amino acid substitutions.
      The evolution rate analyses showed the signature of purifying selection on not
      only different classification level lineages but also the different domains and
      amino acid residue sites of this gene. Also, we suggested that GJA1 gene could be
      used as a good molecular marker to do the phylogenetic reconstruction.

PMID- 19393127
TI  - Breeding without breeding.
AB  - An innovative approach to tree breeding called 'breeding without breeding' (BWB)
      is presented. The method, as applied on the material in hand, allows the capture
      of 75-85% of the genetic response to selection attained through conventional
      programmes without the need to do any controlled pollination and simplified or
      possibly no experimental field testing: both considered to be the most resource
      demanding activities in breeding programmes. BWB combines the use of genotypic or
      phenotypic pre-selection of superior individuals, informative DNA markers for
      fingerprinting and pedigree reconstruction of offspring to assemble naturally
      created full- and half-sib families resulting from mating among selected parents,
      and quantitative genetics analyses to identify elite genotypes for further
      genetic improvement or the establishment of production populations. BWB utility
      is demonstrated using a retrospective study of Douglas-fir (Pseudotsuga
      menziesii) progeny tests consisting of offspring produced from 150 controlled
      crosses among 60 parents and established over three sites. The empirical results
      are supported by theoretical expectations demonstrating anticipated minimum
      genetic response compared with conventional approaches. The method's simplicity
      offers an exceptional opportunity for the development of comparable breeding
      efforts in developing countries, advanced and new breeding programmes, and
      economically important and 'minor' species.

PMID- 19393128
TI  - What do artificial neural networks tell us about the genetic structure of
      populations? The example of European pig populations.
AB  - General and genetic statistical methods are commonly used to deal with
      microsatellite data (highly variable neutral genetic markers). In this paper, the
      self-organizing map (SOM) that belongs to the unsupervised artificial neural
      networks (ANNs) was applied to analyse the structure of 58 European and two
      Chinese pig populations (Sus scrofa) including commercial lines, local breeds and
      cosmopolitan breeds. Results were compared with other unsupervised classification
      or ordination methods such as factorial correspondence analysis, hierarchical
      clustering from an allele sharing distance and the Bayesian genetic model and
      with principal components analysis and neighbour joining from allelic frequencies
      and genetic distances between populations. Like other methods, SOMs were able to
      classify individuals according to their breed origin and to visualize
      similarities between breeds. They provided additional information on the within-
      and between-population diversity, allowed differences between similar populations
      to be highlighted and helped differentiate different groups of populations.

PMID- 19393129
TI  - Influence of local peripheral temporary ischaemia on biochemical and histological
      effects in small intestine and serum of rats following abdominal irradiation.
AB  - The local temporary ischaemia effect on radiation-induced lipid peroxidation,
      superoxide dismutase isoenzyme activities, and intestinal crypt number was
      estimated in male WAG-strain rats in vivo. The animals were irradiated in the
      abdomen area with doses of 2 Gy for ten consecutive days using a Philips 60Co
      source. The calculated dose rate was 0.595 Gy/min. Local temporary ischaemia was
      induced by clamping the tail base before each irradiation. The parameters
      evaluated were: TBA-RS level and enzymatic activities of CuZnSOD, MnSOD in serum
      and jejunum. The number of jejunum crypts was assigned as a histopathologic
      parameter. The results showed a clear protection by ischaemic preconditioning for
      crypt survival. The difference in the number of crypts in irradiated animals with
      and without local temporary ischaemia was statistically significant (Student's t
      test P < 0.05). Also, significant enhancement of TBA-RS was observed in the serum
      of irradiated animals. Local temporary ischaemia application diminished the
      concentration of radiation- induced TBA-RS. The differences in the levels of TBA
      RS in the serum were statistically significant (ANOVA P < 0.002). In contrast,
      there was no evident effect on the level of TBA-RS in tissue homogenates in any
      investigated groups. Some fluctuation of CuZnSOD isoenzyme activity in intestinal
      tissue was noted; however, the differences were not significant. Local temporary
      ischaemia had no influence on Mn- SOD activity in serum, and in both irradiated
      groups the behaviour of this isoenzyme was similar. Also, there were no
      differences in MnSOD activity measured in tissue homogenates. These findings
      support results of our previous in vivo studies, suggesting that local temporary
      ischaemia can prevent oxidative effects of fractionated radiotherapy.

PMID- 19393130
TI  - Re-differentiation of human articular chondrocytes is not enhanced by a rotary
      bioreactor system.
AB  - ACI is the most widely used cell-based surgical procedure for the repair of
      articular cartilage defects. The method is based on in vitro chondrocyte
      cultivation. Two different culture conditions, rotating-wall-vessel bioreactor
      and static culture, were assessed by their effect on the re-differentiation
      potential of human articular chondrocytes seeded into a hydrogel scaffold. Gene
      expression analysis of the tissue-engineered construct revealed no significant
      difference between the tested systems.

PMID- 19393131
TI  - Inhibition of CD44 expression by small interfering RNA to suppress the growth and
      metastasis of ovarian cancer cells in vitro and in vivo.
AB  - Since ovarian cancer cells express CD44, which causes very strong cell adhesion
      to peritoneal mesothelium and an unfavourable prognosis, we designed small
      interfering RNA (siRNA) targeting the CD44 gene to analyse the functional
      consequences of this inhibition in human ovarian cancer. We transfected ovarian
      cancer cell line SKOV-3 with well-designed CD44 siRNA or control siRNA. Western
      blot analysis was used to assess the CD44 expression. Following stable
      transfection, significant inhibition of CD44 expression with 66.13 +/- 4.21 % (P
      < 0.05) in CD44 siRNA1 cells and 62.01 +/- 3.97 % (P < 0.05) in CD44 siRNA2 cells
      was detected. We performed in vitro experiments including cellular adhesion to
      hyaluronan and human peritoneal mesothelial cells, etoposide-induced apoptosis,
      and Boyden chamber invasion assays. The adhesion percentages of CD44 siRNA1 and
      CD44 siRNA2 cells were significantly lower than those of the control siRNA cells
      in adhesion both to hyaluronan and to human peritoneal mesothelium. The CD44
      siRNA transfectants showed significant inhibition of in vitro invasion and loss
      of resistance to apoptosis than the control siRNA cells. In vivo study with
      BALB/c mice was applied to compare the tumour growth and peritoneal
      dissemination. Nude mice treated with CD44 siRNA cells revealed significantly
      lower tumour volume and less peritoneal dissemination compared to mice treated
      with the control siRNA cells. In conclusion, downregulation of CD44 expression by
      siRNA inhibits the in vitro adhesion, invasion and resistance to apoptosis of
      ovarian cancer cells, suppresses tumour growth and peritoneal dissemination of
      human ovarian cancer xenograft in nude mice.

PMID- 19393132
TI  - Multidrug resistance proteins in renal cell carcinoma.
AB  - A large number of renal cancer patients show poor or partial response to
      chemotherapy and the precise mechanism has not been understood yet. MDR is the
      principal mechanism by which many cancers develop resistance to chemotherapeutic
      drugs and is associated with the elevated expression of MDR proteins. These are
      divided into two groups: ABC transporters and non-ABC transporters. The aim of
      our study was to determine the expression of MDR1/Pgp, MRP1 and LRP in 47 samples
      of renal cell carcinomas using immunohistochemical assay. Our results were
      analysed in relation to nuclear grade and other clinical and pathological
      parameters to see the possible correlation between the expression of MDR proteins
      and factors mentioned above. The majority of renal carcinoma specimens showed
      positivity for MDR proteins. In this regard, 21 % of samples revealed positive
      results for MDR1, 62 % for MRP1 and 76.6 % for LRP protein. Furthermore, our
      study displayed significant differences between MDR1, LRP and nuclear grade. On
      the other hand, no association was found between MRP1 and nuclear grade, as well
      as between the expression of three MDR proteins and other clinically relevant
      parameters.

PMID- 19393133
TI  - Influence of COX-2-induced PGE2 on the initiation and progression of tail
      regeneration in Northern House Gecko, Hemidactylus flaviviridis.
AB  - We investigated the role of prostaglandin E2 in reptilian regeneration.
      Prostaglandin E2 is known to play a vital role during wound healing and cell
      proliferation. A significant delay in the rate of growth of regenerate after
      autotomy was observed when the production of prostaglandin E2 was blocked by
      usage of specific cyclooxygenase inhibitors as compared to control animals and
      this delay continued to all the defined stages of regeneration. Therefore,
      prostaglandin E2 could be one of the essential requirements for a successful
      process of regeneration.

PMID- 19393134
TI  - Nucleolar localization of upstream binding factor in HeLa cells depends on rRNA
      synthesis activities.
AB  - During Pol I-mediated rRNA synthesis, UBF plays a key role in transcription.
      Numerous localization studies provided, however, rather divergent results with
      regard to its presence in either of the two structural nucleolar subcompartments,
      FC and DFC. These observations suggest different roles of UBF within nucleoli. In
      order to expand our knowledge in this respect, we have performed the
      ultrastructural localization of UBF and DNA in HeLa cell nucleoli and
      complemented it with mapping DNA/RNA hybrids, which testify for the presence of
      newly synthesized rRNA. With immunogold UBF mapping, the results fell, depending
      on the type of nucleoli, basically into two categories. In nucleoli exhibiting
      one, or at most a few, large FC, UBF molecules were mapped mainly into FC. Such
      nucleoli are known to possess lower activity in rRNA synthesis. In the second
      category of reticulated nucleoli with many tiny FCs, which are characterized by
      high rRNA gene transcription, the gold particles were enriched mainly in DFC/FC
      borders and DFC. The established differential localization of UBF in nucleoli of
      HeLa cells thus has a functional meaning. It reflects both the level of rRNA
      synthesis activities and the architectural role of UBF in nucleoli of these
      cells.

PMID- 19393135
TI  - Systematic review of respite care in the frail elderly.
AB  - OBJECTIVES: To assess the effectiveness and cost-effectiveness of breaks in care
      in improving the well-being of informal carers of frail and disabled older people
      living in the community and to identify carer needs and barriers to uptake of
      respite services. DATA SOURCES: Major electronic databases were searched from the
      earliest possible date to April 2008. REVIEW METHODS: Selected studies were
      assessed and subjected to extraction of numerical data for meta-analysis of
      quantitative studies and extraction of text for thematic analysis of qualitative
      studies. Quality of the studies was assessed using checklists specifically
      designed for the current review. RESULTS: In total, 104 papers were identified
      for inclusion in the quantitative synthesis, 16 of which were appropriate for
      meta-analysis. Carer burden was reduced at 2-6 months' follow-up in single-sample
      studies but not in randomised controlled trials (RCTs) and quasi-experimental
      studies. Depression was reduced in RCTs in the short term and for home care but
      not for day care. These effects, however, were not significant in random-effects
      models. There was a trend for longer interventions to have more positive effects
      than shorter interventions. There was no effect of respite on anxiety, but it had
      positive effects on morale and anger and hostility. Single-group studies
      suggested that quality of life was worse after respite use. There were increased
      rates of institutionalisation after respite use; however, this does not establish
      a causal relationship as it may be a result of respite being provided late in the
      caregiving career. A total of 70 papers were identified for inclusion in the
      qualitative synthesis. Uptake of respite care was influenced by: carer attitudes
      to caring and respite provision; the caregiving relationship; knowledge of, and
      availability of, services; the acceptability to, and impact of respite care on,
      care recipients; hassles resulting from the use of respite care; quality of
      respite care; and the appropriateness and flexibility of service provision.
      Carers expressed needs for active information provision about services, support
      offered early in the caregiving career, access to a variety of services with
      flexible provision, reliable transport services, continuity of care, good-quality
      care, appropriate environments, care that provides benefits for care recipients
      (socialisation and stimulation), and appropriate activities for care recipients'
      levels of abilities and interests. CONCLUSIONS: There was some evidence to
      support respite having a positive effect on carers but the evidence was limited
      and weak. It is difficult, therefore, to make recommendations as to the most
      appropriate form of delivery of respite, apart from the suggestion that a range
      of services is probably most appropriate, to provide flexibility of respite
      provision and responsiveness to carer and care recipient characteristics and
      needs and also changes in those needs over time. There is a need for further high
      quality larger trials that include economic evaluations.

PMID- 19393136
TI  - JACC: Cardiovascular Interventions: the end of the beginning.

PMID- 19393137
TI  - A pebble in a pond.

PMID- 19393138
TI  - Unprotected left main intervention: patient selection, operator technique, and
      clinical outcomes.
AB  - In the 1980s, early attempts at balloon angioplasty of the unprotected left main
      coronary artery (UPLM) were associated with poor early outcomes because of
      coronary dissection, abrupt closure, and restenosis. Mortality rates as high as
      30% at 1 year were reported. In the 1990s, bare-metal stents helped reduce acute
      complications, but high rates of repeat revascularization (20% to 30%) were
      observed because of restenosis. In the early 2000s, the introduction of drug
      eluting stents (DES), with the promise of vastly reduced rates of restenosis,
      raised the possibility of improved late outcomes for UPLM patients receiving
      stents. Although use of DES for UPLM is currently a class III indication in
      patients who are candidates for coronary artery bypass graft (CABG), many
      patients are currently undergoing this procedure. Published registries indicate
      the procedural and in-hospital risks are acceptable and seem to be the same or
      lower than the procedural risks of CABG. Unprotected left main ostial and
      midshaft lesions have excellent early and midterm outcomes that will likely
      (although not yet proven) be similar to those of CABG. Distal left main lesions
      involving the bifurcation are technically more challenging and associated with a
      higher rate of late revascularization. Early registry data have not found excess
      mortality in patients receiving DES for UPLM when compared with historical bypass
      surgery data, even when the distal bifurcation is stented. However, current
      follow-up of stented patients is limited to 1 year or less. Over the next few
      years, the results of randomized trials will expand the evidence base available
      to clinicians caring for this challenging patient group.

PMID- 19393139
TI  - Coronary artery aneurysms after drug-eluting stent implantation.
AB  - Drug-eluting stents (DES), which locally elute antiproliferative drugs, can
      dramatically inhibit neointimal growth. However, several pathological studies
      have indicated that DES may delay healing after vascular injury, and DES
      implantation may be theoretically associated with a risk of coronary artery
      aneurysm formation. Coronary aneurysms have been reported from 3 days to up to 4
      years after DES implantation procedures, with varying clinical presentations. The
      incidence of coronary artery aneurysms after DES implantation is low within the
      first 9 months, with a reported incidence of 0.2% to 2.3%, a rate similar to that
      reported after bare-metal stent (BMS) implantation (0.3% to 3.9%) in the DES
      versus BMS randomized trials. However, the true incidence of coronary aneurysms
      in an unselected patient population is still largely unknown. This article
      reviews the published literature on coronary artery aneurysms specifically
      relating to DES.

PMID- 19393140
TI  - Drug-eluting stenting: the case for post-dilation.
AB  - In clinical practice, adequate stent deployment has an important effect on
      immediate and long-term results after percutaneous coronary interventions. In
      particular, suboptimal or incomplete stent expansion is associated with increased
      restenosis and target vessel revascularization rates and, especially with drug
      eluting stents (DES), might also predispose to stent thrombosis. Notwithstanding
      the significant improvement in technique and materials in the last decade,
      adjunctive high-pressure balloon dilation is still necessary to improve the
      minimum stent area and the uniform volumetric stent expansion in a majority of
      the cases. Indeed, in the published reports, the incidence of incomplete stent
      deployment ranges from 20% to 30% of cases, but it is significantly higher in
      trials in which stent expansion was assessed by intravascular ultrasound.
      Although there are not enough randomized studies about this topic, data from
      published reports continue to support the use of proper post-dilation in the
      majority of patients undergoing both bare-metal stent and DES implantation. This
      review will summarize the different anatomical, clinical, and device-related
      variables for increased risk of suboptimal stent delivery, highlighting the
      importance of adequate high-pressure post-dilation to obtain optimal stent
      expansion to positively affect stent thrombosis and restenosis.

PMID- 19393141
TI  - Drug-eluting stent implantation: technique matters, more than ever.

PMID- 19393142
TI  - Percutaneous coronary intervention for chronic stable angina: a reassessment.
AB  - As it approaches its fourth decade, percutaneous coronary intervention (PCI) is
      now the most widely used revascularization strategy around the world and has been
      tested in multiple clinical scenarios against both medical and surgical
      therapies. For each patient group and clinical scenario setting, the goals of
      therapy must be specifically defined and clearly understood as an integral
      component of the process of selecting the optimal strategy for the individual
      patient. In patients with chronic stable, often mild angina, the major achievable
      goals of PCI are to affect symptoms, either by decreasing them or preventing
      them, reduce the need for subsequent procedures, and relieve ischemia.
      Achievement of these goals has been documented in multiple randomized trials of
      PCI versus medical therapy. In these trials of patients with stable coronary
      artery disease (CAD), however, no reduction in death and myocardial infarction
      has been observed, and these limitations of PCI in this clinical setting need to
      be emphasized. Given the typically diffuse nature of CAD and the fact that PCI
      only treats a segment within a coronary artery, this is not surprising. Although
      optimal medical therapy forms the cornerstone of management for any patient with
      CAD, among stable patients who do fail medical therapy, percutaneous coronary
      revascularization plays a well-documented significant role in improving symptoms
      and preventing the subsequent need for revascularization. The appropriate
      utilization rates of PCI in patients with chronic stable angina and preserved
      left ventricular function should lead to more cost-effective care of patients
      with stable CAD.

PMID- 19393143
TI  - Percutaneous treatment of chronic total coronary occlusions improves regional
      hyperemic myocardial blood flow and contractility: insights from quantitative
      cardiovascular magnetic resonance imaging.
AB  - OBJECTIVES: We sought to investigate temporal changes in contractility and
      hyperemic and resting myocardial blood flow (MBF) in dependent and remote
      myocardium after percutaneous coronary intervention (PCI) of chronic total
      occlusions (CTOs) by using cardiovascular magnetic resonance (CMR) imaging.
      BACKGROUND: Data about the physiological consequences of revascularization of
      CTOs are limited. The use of CMR allows investigation of the regional effects of
      revascularization on MBF and left ventricular contractility. METHODS: We
      prospectively recruited 3 patient groups: 17 patients scheduled for CTO PCI, 17
      scheduled for PCI of a stenosed but nonoccluded coronary artery (non-CTO), and 6
      patients with CTO who were not scheduled for revascularization. All patients
      undergoing PCI underwent CMR imaging <24 h before PCI, with repeat CMR imaging 24
      h and 6 months after PCI. Each CMR scan consisted of cine, perfusion, and delayed
      enhancement imaging. Regional hyperemic and resting MBF, wall thickening, and
      transmural extent of infarction were calculated. RESULTS: In both intervention
      groups, hyperemic MBF in treated segments increased 24 h after PCI compared with
      baseline: CTO group, 2.1 +/- 0.2 ml/min/g versus 1.4 +/- 0.2 ml/min/g (p < 0.01);
      non-CTO group, 2.5 +/- 0.2 ml/min/g versus 1.6 +/- 0.2 ml/min/g (p < 0.01). This
      improvement persisted 6 months after PCI (p < 0.01 for both groups).
      Contractility in treated segments was improved at 24 h and 6 months after CTO PCI
      but only at 6 months after non-CTO PCI. In both intervention groups, treated
      segments no longer had reduced MBF or contractility compared with remote
      segments. In patients with untreated CTO segments, MBF and wall thickening did
      not improve at follow-up. CONCLUSIONS: Successful CTO PCI increases hyperemic MBF
      as early as 24 h after the procedure, with a greater and earlier improvement in
      regional contractility than after non-CTO PCI, despite a greater likelihood of
      irreversible injury in CTO segments.

PMID- 19393144
TI  - Arguments for recanalization of chronic total occlusions.

PMID- 19393146
TI  - Dual antiplatelet and oral anticoagulant therapy: increasing use and precautions
      for a hazardous combination.

PMID- 19393145
TI  - Dual antiplatelet therapy after percutaneous coronary intervention with stent
      implantation in patients taking chronic oral anticoagulation.
AB  - OBJECTIVES: The purpose of this study was to evaluate the safety of dual
      antiplatelet therapy in patients in whom long-term anticoagulation (AC) with
      warfarin is recommended. BACKGROUND: The optimal antithrombotic strategy after
      percutaneous coronary intervention (PCI) for patients receiving AC is unclear.
      METHODS: Consecutive patients who underwent stent implantation and were
      discharged on triple therapy (defined as the combination of aspirin and
      thienopyridines and AC) were analyzed. RESULTS: Of the 127 patients with 224
      lesions, 86.6% were men, with a mean age of 69.9 +/- 8.8 years. Drug-eluting
      stents (DES) were positioned in 71 (55.9%), and bare-metal stents (BMS) were
      positioned in 56 (44.1%) patients. Atrial fibrillation (AF) was the main
      indication (59.1%) for AC treatment. The mean triple therapy duration was 5.6 +/-
      4.6 months, and clinical follow-up was 21.0 +/- 19.8 months. During the triple
      therapy period, 6 patients (4.7%) developed major bleeding complications; 67%
      occurred within the first month. No significant differences between DES and BMS
      were observed in the incidence of major (5.6% vs. 3.6%, respectively, p = 1.0)
      and minor (1.4% vs. 3.6%, respectively, p = 0.57) bleeding and mortality (5.6%
      vs. 1.8%, respectively, p = 0.39). A significant difference was observed in favor
      of DES in target vessel revascularization (14.1% vs. 26.8%, p = 0.041).
      CONCLUSIONS: While receiving triple therapy, major bleeding occurred in 4.7% of
      patients; one-half of the events were lethal, and most occurred within the first
      month.

PMID- 19393147
TI  - Six-month comparison of coronary endothelial dysfunction associated with
      sirolimus-eluting stent versus Paclitaxel-eluting stent.
AB  - OBJECTIVES: This study was designed to investigate whether endothelial
      dysfunction is related to drug-eluting stent (DES) implantation at 6 months after
      stenting. BACKGROUND: Current available DES could delay vessel healing and
      subsequently impair endothelial function. METHODS: Endothelial function was
      estimated at 6-month follow-up in 75 patients (31 men, mean age 62.1 years) with
      a DES (39 sirolimus-eluting stents [SES], 36 paclitaxel-eluting stents [PES]),
      and 10 patients with a bare-metal stent (BMS) to the left anterior descending
      artery, by incremental acetylcholine (Ach) infusion (20 microg/min, 50
      microg/min, 100 microg/min) and nitrate (200 microg/min) into the left coronary
      ostium. Vascular responses were quantitatively measured in arterial segments 5 mm
      proximal and distal to DES and compared with corresponding segments in the BMS
      group and midsegments in the left circumflex artery as a reference nonstented
      artery. All antianginal agents were withheld for at least 72 h before coronary
      angiography. RESULTS: Greater vasoconstriction to Ach was observed in both the
      SES and PES groups than in the BMS group or control segments of left circumflex
      artery. Vasoconstriction to Ach was more prominent in arterial segments distal to
      stents in both SES and PES groups compared with those in the BMS group (p <
      0.001). The degree of vasoconstriction to Ach was similar between the SES and PES
      groups. Endothelium-independent vasodilatation to nitrate did not differ
      significantly between the study groups. CONCLUSIONS: Abnormal vasoconstriction to
      Ach was found in the SES and PES groups, especially in arterial segments distal
      to DES at 6 months after stenting, which suggests that DES has a potential long
      term adverse effect on local coronary endothelial dysfunction.

PMID- 19393148
TI  - Persistent endothelial dysfunction after drug-eluting stents: another continuing
      cost of reducing restenosis.

PMID- 19393149
TI  - Implication of plaque color classification for assessing plaque vulnerability: a
      coronary angioscopy and optical coherence tomography investigation.
AB  - OBJECTIVES: The purpose of this study was to assess the relationship between
      plaque color evaluated by coronary angioscopy and fibrous cap thickness estimated
      by optical coherence tomography (OCT) in vivo. BACKGROUND: Yellow color intensity
      of coronary plaque evaluated by coronary angioscopy might be associated with
      plaque vulnerability. METHODS: Seventy-seven coronary artery plaques in patients
      with acute coronary syndrome were observed by angioscopy and OCT. Plaque color
      was graded as white, light yellow, yellow, or intensive yellow. RESULTS: There
      were significant differences among the groups classified by plaque color with
      respect to the fibrous cap thickness estimated by OCT: 389 +/- 74 mum in white
      plaques, 228 +/- 51 microm in light yellow plaques, 115 +/- 28 microm in yellow
      plaques, and 59 +/- 14 microm in intensive yellow plaques (p < 0.0001). In
      Spearman rank-order correlation analysis, there was a significant negative
      correlation between yellow color intensity and fibrous cap thickness (p <
      0.0001). Furthermore, 80% of intensive yellow plaques were thin cap fibroatheroma
      with a cap thickness of < or =65 microm. CONCLUSIONS: The plaque color in
      coronary angioscopy was determined by the fibrous cap thickness, which was
      assessed by OCT. Although coronary angioscopy remains a specialized research
      tool, it might allow us to evaluate plaque vulnerability.

PMID- 19393150
TI  - Evaluation of a novel slow-release paclitaxel-eluting stent with a bioabsorbable
      polymeric surface coating.
AB  - OBJECTIVES: We sought to evaluate a new second-generation drug-eluting stent
      (DES), comprising a slow-release biodegradable polylactide coglycolide (PLGA)
      polymer and low-dose paclitaxel on a thin-strut cobalt chromium stent platform,
      in a clinically relevant animal model. BACKGROUND: Our previous work demonstrated
      subacute vascular toxicity and necrosis triggering late excess neointima in pig
      coronaries, with a moderate paclitaxel dose eluted from an erodible polymer. The
      use of slower-releasing absorbable polymers with lower doses of paclitaxel is
      expected to minimize such adverse outcomes. METHODS: Three types of stents were
      implanted in pig coronary arteries using quantitative coronary angiography to
      optimize stent apposition: bare-metal stents (BMS); absorbable, slow-release
      polymer-coated-only stents (POLY); and absorbable polymer-based paclitaxel
      eluting stents (PACL). The dose density of paclitaxel was 0.15 microg/mm(2) with
      in vitro studies demonstrating a gradual elution over the course of 12 to 16
      weeks. Animals underwent angiographic restudy and were terminated at 1 and 3
      months for complete histopathologic and histomorphometric analyses. RESULTS: At 1
      month, intimal thickness varied significantly according to stent type, with the
      lowest level for the PACL group compared with the BMS and POLY groups (0.06 +/-
      0.02 mm vs. 0.17 +/- 0.07 mm, 0.17 +/- 0.08 mm, respectively, p < 0.001);
      histological percent area stenosis was 18 +/- 4% for PACL compared with 27 +/- 7%
      for BMS and 30 +/- 12% for POLY, respectively (p = 0.001). At 3 months, PACL
      showed similar neointimal thickness as BMS and POLY (0.09 +/- 0.05 mm vs. 0.13 +/
      0.10 mm and 0.11 +/- 0.03 mm respectively, p = 0.582). Histological percent area
      stenosis was 23 +/- 8% for PACL versus 23 +/- 11% for BMS and 23 +/- 2% for POLY,
      respectively (p = 1.000). CONCLUSIONS: This study shows favorable vascular
      compatibility and efficacy for a novel DES that elutes paclitaxel in porcine
      coronary arteries. These results support the notion that slowing the release rate
      and lowering the dose of paclitaxel favorably influences the vascular biological
      response to DES implant, decreasing early toxicity and promoting stable healing
      while still suppressing neointima formation.

PMID- 19393151
TI  - Systems of care to improve timeliness of reperfusion therapy for ST-segment
      elevation myocardial infarction during off hours: the Mayo Clinic STEMI protocol.
AB  - OBJECTIVES: We implemented the Mayo Clinic ST-segment elevation myocardial
      infarction (STEMI) protocol and evaluated the timeliness of reperfusion therapy
      during off hours versus regular hours. BACKGROUND: Patients with STEMI who
      present during off hours have longer door-to-balloon times and door-to-needle
      times. METHODS: The Mayo STEMI protocol was implemented in May 2004 to optimize
      timeliness of reperfusion therapy for STEMI patients presenting to Saint Mary's
      Hospital, a tertiary facility with on-site percutaneous coronary intervention
      (PCI), and for those presenting to 28 regional hospitals located up to 150 miles
      away from Saint Mary's Hospital. We compared door-to-balloon times and door-to
      needle times for 597 consecutive patients who presented during off hours
      (weekdays from 5 pm to 7 am and any time on weekends or holidays) versus regular
      hours (weekdays from 7 am to 5 pm). In 2003, prior to implementing the protocol,
      median door-to-balloon time at Saint Mary's Hospital was 85 min during regular
      hours and 98 min during off hours. RESULTS: Among 258 patients who presented to
      Saint Mary's Hospital, median door-to-balloon time was 65 min during regular
      hours versus 74 min during off hours (p = 0.085). Among 105 patients transferred
      from regional hospitals for primary PCI, median door-to-balloon time was 118 min
      during regular hours versus 114 min during off hours (p = 0.15). Among 131
      patients treated with fibrinolytic therapy at regional hospitals, median door-to
      needle time was 21 min during regular hours versus 26 min during off hours (p =
      0.067). CONCLUSIONS: The Mayo Clinic STEMI protocol demonstrates the rapid times
      that can be achieved through coordinated systems of care for STEMI patients
      presenting during off hours and regular hours.

PMID- 19393152
TI  - A campaign to improve the timeliness of primary percutaneous coronary
      intervention: Door-to-Balloon: An Alliance for Quality.
AB  - OBJECTIVES: We sought to describe the rationale and methods for Door-to-Balloon
      (D2B): An Alliance for Quality, an international effort organized by the American
      College of Cardiology in partnership with the American Heart Association and 37
      other organizations to rapidly translate research about how best to achieve
      outstanding D2B times for patients with ST-segment elevation myocardial
      infarction (STEMI) into practice. BACKGROUND: The D2B time, the time between
      hospital arrival and primary percutaneous coronary intervention for patients with
      STEMI, is strongly associated with the likelihood of survival, yet the majority
      of patients are not treated within the guideline-recommended time of </=90 min.
      Recent research has revealed key and underused strategies that are associated
      with achieving faster D2B times. METHODS: The D2B Alliance has enrolled
      approximately 1,000 hospitals. Its goal is to achieve a D2B time of </=90 min for
      at least 75% of non-transferred patients. The key strategies chosen by the D2B
      Alliance include having the emergency medicine physician activate the
      catheterization laboratory with a single call, having the team prepared within 20
      to 30 min of the call; rapid data feedback; a team-based approach; and
      administrative support. The use of a pre-hospital electrocardiogram by emergency
      medical services personnel to activate the catheterization laboratory was also
      noted as an additional optional strategy. The project has many approaches to
      promote participation and adoption of effective strategies. An evaluation
      component is also described. CONCLUSIONS: The design of the D2B: An Alliance for
      Quality, a novel campaign to improve D2B time, is described.

PMID- 19393153
TI  - Tardy Pardee: moving medical effectiveness to the forefront.

PMID- 19393154
TI  - First percutaneous catheter intervention for left main coronary artery disease:
      30 years ago.

PMID- 19393155
TI  - Completed preparative separation of alkaloids from Cephaltaxus fortunine by step
      pH-gradient high-speed counter-current chromatography.
AB  - Cephalotaxine-type alkaloids are the anti-cancer components in twigs, leaves,
      roots and seeds of Cephalotaxus fortunine. It is very important to use the
      limited resource by finding an efficient purification technology of the
      alkaloids. Separation of cephalotaxine-type alkaloids in Cephalotaxus fortunine
      by step-pH-gradient high-speed counter-current chromatography (step-pH-gradient
      HSCCC) was studied in this paper. The step-pH-gradient HSCCC was performed on a
      HSCCC instrument equipped with a 400-mL column, using the upper phase of ethyl
      acetate-n-hexane-water, with added 0.01% trifluoroacetic acid (TFA) as stationary
      phase, and the lower phase of ethyl acetate-n-hexane-water, with added 2%
      NH(4)OH, 0.2% NH(4)OH and 0.05% TFA as mobile phase. For each separation, 800mg
      of extract of cephalotaxine-type alkaloids was separated to yield 9.3mg of
      drupacine, 15.9mg of wilsonine, 130.4mg of cephalotaxine, 64.8mg of epi
      wilsonine, 12.8mg of fortunine and 35.6mg of acetylcephalotaxine with purities
      81.2%, 85.7%, 95.3%, 97.5%, 89.1% and 96.2%, respectively. The recovery of each
      alkaloid was more than 90%. The structures of the six alkaloids were identified
      by electrospray ionization mass spectrum (ESI-MS) and (1)H and (13)C NMR.

PMID- 19393156
TI  - Analysis of permethrin isomers in composite diet samples by molecularly imprinted
      solid-phase extraction and isotope dilution gas chromatography-ion trap mass
      spectrometry.
AB  - Determination of an individual's aggregate dietary ingestion of pesticides
      entails analysis of a difficult sample matrix. Permethrin-specific molecularly
      imprinted polymer (MIP) solid-phase extraction cartridges were developed for use
      as a sample preparation technique for a composite food matrix. Vortexing with
      acetonitrile and centrifugation were found to provide optimal extraction of the
      permethrin isomers from the composite foods. The acetonitrile (with 1% acetic
      acid) was mostly evaporated and the analytes reconstituted in 90:10
      water/acetonitrile in preparation for molecularly imprinted solid-phase
      extraction. Permethrin elution was accomplished with acetonitrile and sample
      extracts were analyzed by isotope dilution gas chromatography-ion trap mass
      spectrometry. Quantitation of product ions provided definitive identification of
      the pesticide isomers. The final method parameters were tested with fortified
      composite food samples of varying fat content (1%, 5%, and 10%) and recoveries
      ranged from 99.3% to 126%. Vegetable samples with incurred pesticide levels were
      also analyzed with the given method and recoveries were acceptable (81.0-95.7%).
      Method detection limits were demonstrated in the low ppb range. Finally, the
      applicability of the MIP stationary phase to extract other pyrethroids,
      specifically cyfluthrin and cypermethrin, was also investigated.

PMID- 19393157
TI  - Molecular machinery of signal transduction and cell cycle regulation in
      Plasmodium.
AB  - The regulation of the Plasmodium cell cycle is not understood. Although the
      Plasmodium falciparum genome is completely sequenced, about 60% of the predicted
      proteins share little or no sequence similarity with other eukaryotes. This
      feature impairs the identification of important proteins participating in the
      regulation of the cell cycle. There are several open questions that concern cell
      cycle progression in malaria parasites, including the mechanism by which multiple
      nuclear divisions is controlled and how the cell cycle is managed in all phases
      of their complex life cycle. Cell cycle synchrony of the parasite population
      within the host, as well as the circadian rhythm of proliferation, are striking
      features of some Plasmodium species, the molecular basis of which remains to be
      elucidated. In this review we discuss the role of indole-related molecules as
      signals that modulate the cell cycle in Plasmodium and other eukaryotes, and we
      also consider the possible role of kinases in the signal transduction and in the
      responses it triggers.

PMID- 19393159
TI  - Homology, paralogy and function of DGF-1, a highly dispersed Trypanosoma cruzi
      specific gene family and its implications for information entropy of its encoded
      proteins.
AB  - Surface adhesion proteins are essential for Trypanosoma cruzi invasion of
      mammalian cells. Here we show that Dispersed Gene Family-1 (DGF-1) members,
      previously identified as nuclear repeated sequences present in several
      chromosomes and comprising the third largest T. cruzi specific gene family, have
      conserved adhesin motifs including four segments with significant similarity to
      human beta 7 integrin. Flow cytometry and biotinylation assays with anti-DGF-1
      antibodies indicated that, as expected, DGF-1 members are expressed on the
      trypomastigote surface. The DGF-1 genealogy, inferred using T. cruzi Genome
      Project data and network phylogeny algorithms, suggests that this gene family is
      separated in at least three groups with differential distribution of functional
      domains. To identify which members of this gene family are expressed we used a
      combined approach of RT-PCR and codon usage profiles, showing that expressed
      members have a very biased codon usage favoring GC, whereas non-expressed members
      have a homogeneous distribution. Shannon information entropy was used to measure
      sequence variability and revealed four major high entropy segments in the
      extracellular domain of DGF-1 overlapping with important putative functional
      modules of the predicted proteins. Testing for natural selection, however,
      indicated that these high entropy segments were not under positive selection,
      which contradicts the notion that positive selection is the cause of high
      variability in specific domains of a protein relative to other less variable
      regions in the same molecule. We conjectured that members of the DGF-1 family
      might be associated with the ability of T. cruzi to bind extracellular matrix
      proteins, such as fibronectin and laminin, and speculated on mechanisms that
      would be generating the localized diversity in these molecules in the absence of
      selection.

PMID- 19393158
TI  - Successful parasitism of vector snail Biomphalaria glabrata by the human blood
      fluke (trematode) Schistosoma mansoni: a 2009 assessment.
AB  - Schistosomiasis, caused by infections by human blood flukes (Trematoda),
      continues to disrupt the lives of over 200,000,000 people in over 70 countries,
      inflicting misery and precluding the individuals' otherwise reasonable
      expectations of productive lives. Infection requires contact with freshwater in
      which infected snails (the intermediate hosts of schistosomes) have released
      cercariae larvae. Habitats suitable for the host snails continue to expand as a
      consequence of water resource development. No vaccine is available, and
      resistance has emerged towards the single licensed schistosomicide drug. Since
      human infections would cease if parasite infections in snails were prevented,
      efforts are being made to discover requirements of intra-molluscan development of
      these parasites. Wherever blood flukes occur, naturally resistant conspecific
      snails are present. To understand the mechanisms used by parasites to ensure
      their survival in immunocompetent hosts, one must comprehend the interior defense
      mechanisms that are available to the host. For one intermediate host snail
      (Biomphalaria glabrata) and trematodes for which it serves as vector, molecular
      genetic and proteomic surveys for genes and proteins influencing the outcomes on
      infections are yielding lists of candidates. A comparative approach drawing on
      data from studies in divergent species provides a robust basis for hypothesis
      generation to drive decisions as to which candidates merit detailed further
      investigation. For example, reactive oxygen and nitrogen species are known
      mediators or effectors in battles between infectious agents and their hosts. An
      approach targeting genes involved in relevant pathways has been fruitful in the
      Schistosoma mansoni -- B. glabrata parasitism, leading to discovery of a
      functionally relevant gene set (encoding enzymes responsible for the leukocyte
      respiratory burst) that associates significantly with host resistance phenotype.
      This review summarizes advances in the understanding of strategies used by both
      this trematode parasite and its molluscan host to ensure their survival.

PMID- 19393160
TI  - Whole-genome comparative RNA expression profiling of axenic and intracellular
      amastigote forms of Leishmania infantum.
AB  - Leishmania parasites cycle between the alimentary tract of a sandfly vector as
      free-living promastigotes and the acidified phagolysosomes of the vertebrate host
      macrophage as aflagellated amastigotes. The differentiation process can be
      mimicked in host-free culture by switching promastigotes (e.g. 25 degrees C,
      neutral pH) to a phagolysosomal-like environment (e.g. 37 degrees C, acidic pH
      and 5% CO(2)) for certain, but not all Leishmania species. Axenically grown
      amastigotes have been shown to share several morphological and biochemical
      characteristics with macrophage-derived intracellular amastigotes. In this study,
      we used a DNA oligonucleotide full-genome array to compare global RNA expression
      profiling of Leishmania infantum axenic amastigotes to intracellular amastigotes
      derived from infected macrophages. In general, 40% more genes (518 genes vs. 309
      genes) were found upregulated in axenic amastigotes compared to intracellular
      amastigotes. Comparisons in expression profiling between axenic amastigotes and
      intracellular amastigotes revealed substantial differences in regulated mRNA
      abundance. Remarkably, among the differentially upregulated transcripts only 12%
      were common to both amastigote preparations. The major differences between axenic
      and intracellular amastigotes were observed in metabolic process, especially in
      fatty acid metabolism, in intracellular transport and membrane vesicular fusion,
      in proteolysis, in the number and type of protein kinases and RNA binding
      proteins and in the response to oxidative stress. These findings highlight the
      importance of the host macrophage in driving the parasite to specific
      adaptations, which consequently result in highly regulated changes in gene
      expression.

PMID- 19393161
TI  - Leishmania major lacking arginase (ARG) are auxotrophic for polyamines but retain
      infectivity to susceptible BALB/c mice.
AB  - Polyamines are essential metabolites in eukaryotes participating in a variety of
      proliferative processes, and in trypanosomatid protozoa play an additional role
      in the synthesis of the critical thiol trypanothione. Whereas the polyamine
      biosynthesis arising from L-ornithine has been well studied in protozoa, the
      metabolic origin(s) of L-ornithine have received less attention. Arginase (EC
      3.5.3.1) catalyzes the enzymatic hydrolysis of L-arginine to L-ornithine and
      urea, and we tested the role of arginase in polyamine synthesis by the generation
      of an arg(?) knockout in Leishmania major by double targeted gene replacement.
      This mutant lacked arginase activity and required the nutritional provision of
      polyamines or L-ornithine for growth. A complemented line (arg(?)/+ARG)
      expressing arginase from a multi-copy expression vector showed 30-fold elevation
      of arginase activity, similar polyamine and ornithine levels as the wild-type,
      and resistance to the inhibitors ?-difluoromethylornithine (DFMO) and N(?)
      hydroxy-l-arginine (NOHA). This established that arginase is the major route of
      polyamine synthesis in promastigotes cultured in vitro. The arg(?) parasites
      retained the ability to differentiate normally to the infective metacyclic stage,
      and were able to induce progressive disease following inoculation into
      susceptible BALB/c mice, albeit less efficiently than WT parasites. These data
      suggest that the infective amastigote form of Leishmania, which normally resides
      within an acidified parasitophorous vacuole, can survive in vivo through salvage
      of host polyamines and/or other molecules, aided by the tendency of acidic
      compartments to concentrate basic metabolites. This may thus contribute to the
      relative resistance of Leishmania to ornithine decarboxylase (ODC) inhibitors.
      The availability of infective, viable, arginase-deficient parasites should prove
      useful in dissecting the role of l-arginine metabolism in both pro- and anti
      parasitic responses involving host nitric oxide synthase, which requires L
      arginine to generate NO.

PMID- 19393162
TI  - Mutational studies reveal lysine 352 on the large subunit is indispensable for
      catalytic activity of bi-subunit topoisomerase I from Leishmania donovani.
AB  - From the vanadate complex crystal structure of Leishmania donovani topoisomerase
      I, several amino acid residues have been implicated to be involved in the
      catalytic reaction. Although several predictions and propositions have been made,
      the exact role of these amino acids has not yet been clearly demonstrated in
      vitro. Among these residues, lysine 352 and arginine 314 stand as potential
      candidates for playing the role of a general acid during the cleavage step. In
      this study, we have characterized the role of lysine 352 on the large subunit, by
      site-directed mutagenesis and have tried to identify the general acid that can
      protonate the 5?-O atom of the leaving strand. Studies with the mutant enzymes
      reveal that, relaxation activity was severely affected when Lys352 was mutated to
      arginine or alanine (K352R or K352A). Mutation of Arg314 to Lys (R314K) has very
      little effect on the relaxation activity. Detailed study reveals that, both
      cleavage and religation steps are severely affected in case of K352R and K352A
      and the cleavage religation equilibrium is shifted towards the cleavage. On the
      contrary, the R314K mutant exhibits only a slightly slower rate of cleavage
      compared to wild-type enzyme. Cleavage assays with an oligonucleotide containing
      5?-bridging phosphorothiolate indicate that Lys352 acts as a general acid in the
      cleavage step. Altogether, this study establishes the indispensable role of
      lysine 352 in the catalytic reaction of L. donovani topoisomerase I.

PMID- 19393165
TI  - Gene silencing of nfa1 affects the in vitro cytotoxicity of Naegleria fowleri in
      murine macrophages.
AB  - The gene nfa1 was isolated from the free-living pathogenic amoeba Naegleria
      fowleri. The protein Nfa1 is located in pseudopodia and specifically in food
      cups. It is also involved in cytotoxicity. In this study, we used synthetic small
      interfering RNAs (siRNA) to examine the effects of nfa1 down-regulation. We
      observed the expression of nfa1 mRNA and Nfa1 protein using Northern and Western
      blots. We also examined the effects of nfa1 down-regulation on the in vitro
      cytotoxicity of N. fowleri. Four synthetic siRNAs were constructed, and of those,
      sinfa1-1 showed the highest down-regulation of an nfa1 mRNA and Nfa1 protein by
      70 and 43%, respectively. In order to achieve long-lasting silencing of the
      transfected genes, we constructed two vectors which were pAct/SAGAH and
      pAct/asnfa1AGAH cloned with the sinfa1-1 and an antisense RNA to the nfa1 gene.
      In N. fowleri transfected with pAct/SAGAH, FACS revealed a 60 and 57% reduction
      in nfa1 mRNA and Nfa1 protein levels, respectively. To determine whether the Nfa1
      proteins were related with in vitro cytotoxicity, LDH assays were used and showed
      that the cytotoxicity of these transfectants to macrophages was reduced by 26.4
      and 36.2% at 17 and 24h, respectively. Moreover, after transfection with
      pAct/asnfa1AGAH, amoebic cytotoxicity decreased by 8.2 and 10% at 17 and at 24h,
      respectively. This is the first report to show the RNA interference in N. folweri
      trophozoites and also demonstrate the Nfa1 function in vitro for its
      cytotoxicity.

PMID- 19393164
TI  - Schistosomin from the snail Biomphalaria glabrata: expression studies suggest no
      involvement in trematode-mediated castration.
AB  - By inhibiting reproductive hormones, the neuropeptide schistosomin produced by
      the snail Lymnaea stagnalis plays an essential role in parasitic castration
      mediated by the schistosome parasite Trichobilharzia ocellata during late stage
      infection. Here we report on the presence and expression of schistosomin in the
      snail Biomphalaria glabrata, a prominent intermediate host of the parasite
      Schistosoma mansoni, one of the causative agents of human schistosomiasis. The
      deduced amino acid (aa) sequences from complementary DNAs (cDNAs) from B.
      glabrata contain a 17 aa signal peptide and a 79 aa mature peptide with 62 -- 64%
      identity to schistosomin from L. stagnalis. Ontogenic expression at the protein
      and mRNA levels showed that schistosomin was in higher abundance in embryos and
      juveniles relative to mature snails, suggesting that schistosomin is likely
      involved in developmental processes, not in reproduction. Moreover, expression
      data demonstrated that infection with two different digenetic trematodes, S.
      mansoni and Echinostoma paraensei, did not provoke elevated expression of
      schistosomin in B. glabrata from early stage infection (4 days post-exposure;
      dpe) to patent infection (up to 60dpe), by which time parasitic castration has
      been accomplished. In conclusion, our data suggest that a role of schistosomin in
      parasitic castration cannot be established in B. glabrata infected with either of
      two trematode species.

PMID- 19393163
TI  - Lipidomic analysis reveals that phosphatidylglycerol and phosphatidylethanolamine
      are newly generated phospholipids in an early-divergent protozoan, Giardia
      lamblia.
AB  - The pathogenic protozoan Giardia lamblia is known to not synthesize membrane
      lipids de novo. Therefore, it is possible that lipids in the small intestine,
      where trophozoites colonize, play key roles in regulating the growth and
      differentiation of this important pathogen. The focus of the current study is to
      conduct a complete lipidomic analysis and to test the hypothesis that Giardia has
      some ability to generate new phospholipids (PLs). Using mass spectrometry, now we
      show that phosphatidylglycerols (PGs) are major PLs followed by
      phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) in non-encysting
      and encysting trophozoites, as well in cysts. The fatty acids attached to these
      PLs consist mostly of palmitate, palmitoleate, oleate, and linoleate. Results
      also indicate that PGs and PEs, unlike PCs, are not present in bovine bile and
      serum, the major sources of lipids of the culture medium, and that they could
      therefore be produced by fatty acid and headgroup remodeling reactions,
      circumventing the synthesis of entirely new PLs via de novo pathways. Genomic and
      transcriptional analyses show the presence of giardial
      phosphatidylglycerolphosphate synthase (gpgps) and phosphatidylserine
      decarboxylase (gpsd) genes, which are expressed throughout the life cycle.
      Bioinformatic and phylogenetic analyses further indicated that both genes are of
      prokaryotic origin and that they have undergone duplication in the course of
      evolution. Our studies suggest that the abundance of PG in Giardia is unique
      among eukaryotes and that its synthesis thus could serve as a potential target
      for developing new therapies against this waterborne parasite.

PMID- 19393166
TI  - Bacterial thermostable beta-glucanases as a tool for plant functional genomics.
AB  - A new strategy for creating experimental models for functional genomics has been
      proposed. It is based on the expression in transgenic plants of genes from
      thermophilic bacteria encoding functional analogues of plant proteins with high
      specific activity and thermal stability. We have validated this strategy by
      comparing physiological, biochemical and molecular properties of control tobacco
      plants and transgenic plants expressing genes of beta-glucanases with different
      substrate specificity. We demonstrate that the expression of bacterial beta-1,3
      1,4-glucanase gene exerts no significant influence on tobacco plant metabolism,
      while the expression of bacterial beta-1,3-glucanase affects plant metabolism
      only at early stages of growth and development. By contrast, the expression of
      bacterial beta-1,4-glucanase has a significant effect on transgenic tobacco plant
      metabolism, namely, it affects plant morphology, the thickness of the primary
      cell wall, phytohormonal status, and the relative sugar content. We propose a
      hypothesis of beta-glucanase action as an important factor of genetic regulation
      of metabolic processes in plants.

PMID- 19393167
TI  - MUST: a system for identification of miniature inverted-repeat transposable
      elements and applications to Anabaena variabilis and Haloquadratum walsbyi.
AB  - Transposable elements (TE) are functionally important genetic elements that can
      move within a genome. Miniature inverted-repeat transposable elements (MITEs)
      constitute a class of transposable elements that are usually small in size and
      have high numbers of conserved copies. Identifying all the MITEs in a genome
      could provide new insights about gene evolution and genome dynamics of the
      organism. We present a web-based MITE Uncovering SysTem (MUST) for prediction and
      analyses of MITEs at a genome level. MUST reliably found both the previously
      known and novel MITEs in the two bacterial genomes, Anabaena variabilis ATCC
      29413 and Haloquadratum walsbyi DSM 16790. MUST is available at
      http://csbl1.bmb.uga.edu/ffzhou/MUST/ (the standalone version is available upon
      request). Supplementary data associated with this article are available in the
      online version or at: http://csbl1.bmb.uga.edu/ffzhou/MUST/supp/.

PMID- 19393171
TI  - Rapid proteasomal degradation of transcription factor IIB in accordance with F9
      cell differentiation.
AB  - We found that the levels of all general transcription factors (GTFs) for RNA
      polymerase II decreased in F9 cells when the cells were subjected to a
      differentiation procedure. Different from other GTFs, decrease of TFIIB during
      the differentiation was suppressed by addition of a proteasome inhibitor, MG132.
      The half-life of TFIIB in the differentiated cells was remarkably reduced
      compared with that in the undifferentiated cells. Moreover, it was demonstrated
      that TFIIB is a poly-ubiquitinated protein. Results of this study suggest that
      components of the transcription machinery decreased in accordance with cell
      differentiation and that TFIIB is specifically and rapidly degraded by the
      ubiquitin-proteasome pathway.

PMID- 19393168
TI  - Histone acetyltransferase Hbo1: catalytic activity, cellular abundance, and links
      to primary cancers.
AB  - In addition to the well-characterized proteins that comprise the pre-replicative
      complex, recent studies suggest that chromatin structure plays an important role
      in DNA replication initiation. One of these chromatin factors is the histone
      acetyltransferase (HAT) Hbo1 which is unique among HAT enzymes in that it serves
      as a positive regulator of DNA replication. However, several of the basic
      properties of Hbo1 have not been previously examined, including its intrinsic
      catalytic activity, its molecular abundance in cells, and its pattern of
      expression in primary cancer cells. Here we show that recombinant Hbo1 can
      acetylate nucleosomal histone H4 in vitro, with a preference for lysines 5 and
      12. Using semi-quantitative western blot analysis, we find that Hbo1 is
      approximately equimolar with the number of active replication origins in normal
      human fibroblasts but is an order of magnitude more abundant in both MCF7 and
      Saos-2 established cancer cell lines. Immunohistochemistry for Hbo1 in 11 primary
      human tumor types revealed strong Hbo1 protein expression in carcinomas of the
      testis, ovary, breast, stomach/esophagus, and bladder.

PMID- 19393172
TI  - The rapid evolution of signal peptides is mainly caused by relaxed selection on
      non-synonymous and synonymous sites.
AB  - The precursor of a secretory protein usually contains an N-terminal signal
      peptide (SP), which directs the protein to cross the membrane. We performed a
      genome-wide analysis of secretory proteins in prokaryotes and eukaryotes, and
      found that signal peptides evolved faster than mature proteins. To determine
      whether the evolutionary pattern could be explained by selective pressure
      changes, we studied the amino acid replacements in signal peptides. We found that
      they tend to be more conserved than those in mature regions of the proteins,
      suggesting relaxed selective pressure acting on non-synonymous sites. This is
      potentially explained by similar biochemical requirements of signal peptides. We
      also observed a decreased codon adaptation index (CAI), suggesting a relaxed
      purifying selection on synonymous sites of signal peptides. In addition, the
      evolutionary rate of signal sequences increases with codon usage bias, suggesting
      that increased rare codon frequency in signal peptides is a result of natural
      selection to improve secretion efficiency. Evidence also suggests signal peptides
      might have undergone positive selection. In summary, the evolution of signal
      peptides may be caused by a mixture of selection forces, primarily relaxation of
      purifying selection.

PMID- 19393173
TI  - Chronology of the extant African elephant species and case study of the species
      identification of the small African elephant with the molecular phylogenetic
      method.
AB  - Despite vigorous genetic studies of African elephants (Loxodonta africana and L.
      cyclotis) during the last decade, their evolutionary history is still obscure.
      Phylogenetic studies and coalescence time estimation using longer nucleotide
      sequence data from denser samplings are necessary to better understand the
      natural history of African elephants. Further, species identification among
      African elephants is sometimes very difficult using only the external
      morphological characteristics. This is a serious problem for making an adequate
      breeding plan in zoological gardens. In this paper, we investigated the continent
      wide phylogeographical pattern of the African elephants and estimated the
      coalescence times among them. From these molecular data and geological evidence,
      we proposed an evolutionary scenario for the African elephants. We further
      demonstrated the effectiveness of molecular phylogenetic methods in species
      identification.

PMID- 19393174
TI  - Repetitive DNA elements, nucleosome binding and human gene expression.
AB  - We evaluated the epigenetic contributions of repetitive DNA elements to human
      gene regulation. Human proximal promoter sequences show distinct distributions of
      transposable elements (TEs) and simple sequence repeats (SSRs). TEs are enriched
      distal from transcriptional start sites (TSSs) and their frequency decreases
      closer to TSSs, being largely absent from the core promoter region. SSRs, on the
      other hand, are found at low frequency distal to the TSS and then increase in
      frequency starting approximately 150 bp upstream of the TSS. The peak of SSR
      density is centered around the -35 bp position where the basal transcriptional
      machinery assembles. These trends in repetitive sequence distribution are
      strongly correlated, positively for TEs and negatively for SSRs, with relative
      nucleosome binding affinities along the promoters. Nucleosomes bind with highest
      probability distal from the TSS and the nucleosome binding affinity steadily
      decreases reaching its nadir just upstream of the TSS at the same point where SSR
      frequency is at its highest. Promoters that are enriched for TEs are more highly
      and broadly expressed, on average, than promoters that are devoid of TEs. In
      addition, promoters that have similar repetitive DNA profiles regulate genes that
      have more similar expression patterns and encode proteins with more similar
      functions than promoters that differ with respect to their repetitive DNA.
      Furthermore, distinct repetitive DNA promoter profiles are correlated with tissue
      specific patterns of expression. These observations indicate that repetitive DNA
      elements mediate chromatin accessibility in proximal promoter regions and the
      repeat content of promoters is relevant to both gene expression and function.

PMID- 19393175
TI  - Multiple duplication of the bucentaur gene family, which recruits the APE-like
      domain of retrotransposon: Identification of a novel homolog and distinct
      cellular expression.
AB  - The p97bcnt/cfdp2 is a ruminant-specific gene created by a combination of gene
      duplication of ancestral bcnt (bucentaur) or cfdp1 (craniofacial developmental
      protein 1), bcnt/cfdp1, and the insertion of a retrotransposable element-1 (RTE).
      As a result, p97Bcnt recruits the whole apurinic/apyrimidinic endonuclease (APE)
      like domain of RTE in the middle of the molecule (RTE domain) as a region encoded
      by an exon. In addition, p97Bcnt contains two intramolecular repeats (IRs) of 40
      amino acids each in the C-terminal region, whereas Bcnt/Cfdp1 contains one IR. We
      have identified an additional bovine homolog with a structure highly similar to
      p97Bcnt, designated p97Bcnt2, which contains three IRs. p97bcnt2 is located in
      tandem with bcnt/cfdp1 and p97bcnt within a 177-kb range on bovine chromosome 18,
      a syntenic region of human chromosome 16. The gene product is expressed as a
      protein with an apparent molecular mass of 102 kDa. The phylogenetic tree
      strongly suggests that p97bcnt-2 forms a third clade of the bcnt family and that
      the first duplication of the IR unit occurred prior to the divergence of p97bcnt
      and p97bcnt-2. To address the question of whether these bcnt members have
      distinct functions, we first examined the expression and localization of the
      p97Bcnt family members. p97Bcnt is substantially expressed in many tissues
      involved in responses to external and internal stress. In the testis, p97Bcnt
      localizes preferentially in the nuclei of spermatozoa, while Bcnt/Cfdp1 localizes
      predominantly in the cytosol of Leydig cells and some spermatogenic cells,
      implying that at least these two molecules of the Bcnt family play different
      functional roles. These results provide evidence for the direct contribution of
      RTE to gene diversity to form gene families that may support cellular function.

PMID- 19393176
TI  - The evolutionary study of small RNA-directed gene silencing pathways by
      investigating RNase III enzymes.
AB  - The RNA-mediated gene silencing pathways are evolutionarily conserved processes.
      They highlight a fundamental role of short RNAs in eukaryotic gene regulation and
      antiviral defense. Recently three distinct small RNA-directed silencing pathways
      are observed, such as the destruction of mRNA via siRNA, inhibition of mRNA
      translation via miRNA, and epigenetic gene silencing via siRNA. It was also found
      that in these pathways, the members of ribonuclease III family play important
      roles in diverse RNA maturation and decay. Here we investigated the evolution of
      RNase III nucleases, Dicer as representative, to further figure out the
      evolutionary relationship of these three gene silencing pathways. With the
      advantage of using genomic sequences as the subject in homolog search, in un
      annotated genomic regions, we were able to detect possible candidates for 3
      functional domains and genes of dicer and drosha. Moreover, we found that
      prokaryotes including eubacteria and archaea lack completely the PAZ domain of
      Dicer. These results show the taxonomic-dependent evolution of the RNA-mediated
      gene silencing pathways.

PMID- 19393177
TI  - Molecular cloning of endogenous beta-glucosidase from common Japanese brackish
      water clam Corbicula japonica.
AB  - Studies on the cellulose utilization by animals have been conducted in keeping
      with the recent developments in molecular biology. In mollusks, endogenous
      cellulases have been reported from blue mussel, abalone, and freshwater snail. We
      previously reported the possibility of cellulose assimilation by Corbicula
      japonica, a representative bivalve dominant in brackish water environments in
      Japan, and the cloning of its endogenous cellulase (beta-1,4-glucanase) gene
      (Sakamoto, K., Touhata, K., Yamashita, M., Kasai, A. and Toyohara, H., 2007.
      Cellulose digestion by common Japanese freshwater clam Corbicula japonica. Fish.
      Sci. 73, 675-683). However, the gene of beta-glucosidase, another enzyme
      essential for the complete cellulose decomposition to glucose units, has not yet
      been isolated from the mollusk. Therefore, we attempted the molecular cloning of
      endogenous beta-glucosidase from C. japonica and succeeded in the isolation of a
      cDNA with a 2832-bp open reading frame (ORF) encoding 943 amino acid residues
      (CjCel1A). CjCEL1A has 2 repeated GHF-1(Glycosyl Hydrolase family 1)-like domains
      and showed high similarity with known insect beta-glucosidases and mammalian
      lactase-phlorizin-hydrolases. Reverse transcription (RT)-PCR analysis and in situ
      hybridization revealed that CjCEL1A is likely to be produced in the secretory
      cells in the digestive gland, suggesting that CjCEL1A is a digestive beta
      glucosidase of C. japonica and is not derived from symbionts.

PMID- 19393178
TI  - Structural and functional characterizations of an Activin type II receptor
      orthologue from the pacific oyster Crassostrea gigas.
AB  - Members of the Transforming Growth factor beta (TGF-beta) superfamily of cell
      signalling polypeptides are known to play important roles in cell proliferation
      and differentiation during development and in various physiological processes of
      most animal clades. Recent findings in the mollusc Crassostrea gigas demonstrate
      the occurrence of a diversity of TGF-beta signalling components including various
      ligands, three type I receptors but only a single type II receptor. This report
      describes the characterization of Cg-ActRII, a new type II receptor displaying
      homology with vertebrate and Drosophila Activin type II receptors. The use of
      zebrafish embryo as a reporter organism revealed that, in a way similar to its
      zebrafish counterpart, overexpression of Cg-ActRII or its dominant negative
      acting truncated form resulted in a dose dependent range of dorsoventral defects
      coupled with anterior disorders. Expression pattern of Cg-ActRII transcripts
      examined by real time PCR and in situ PCR in C. gigas showed high levels of Cg
      ActRII transcripts in early embryonic stages and in the developing larval central
      nervous system. Except for a high expression in the visceral ganglia, most oyster
      adult tissues displayed rather low levels of transcripts. Altogether, the data
      suggest a high degree of conservation at both the structural and functional
      levels during evolution for this class of receptors.

PMID- 19393179
TI  - Origin and dispersal of atypical aldehyde dehydrogenase ALDH2487Lys.
AB  - The East Asian respond with a marked facial flushing and mild to moderate
      symptoms of intoxication after drinking the amounts of alcohol that has no
      detectable effect on European. The alcohol sensitivity in Orientals is due to a
      delayed oxidation of acetaldehyde by an atypical aldehyde dehydrogenase
      ALDH2487Lys, which is resulted from a structural mutation in gene ALDH2. The
      atypical ALDH2487Lys allele has been associated with various phenotypic statuses,
      such as protective against alcohol dependence and the risk of alcohol-related
      digestive tract cancers. Here, we have examined this SNP, adjacent four non
      coding SNPs, and one downstream STRP on ALDH2 gene, in total of 1072 unrelated
      healthy individuals from 14 Chinese populations and 130 Indian individuals. Five
      major haplotypes based on five SNPs across the ALDH2 gene 40 kb were found in all
      East Asian populations. The frequencies of the ancestral haplotype GCCTG and the
      East Asian special haplotype GCCTA containing the atypical ALDH2487Lys allele
      were 44.8% and 14.9%, respectively. The frequency of the atypical ALDH2487Lys
      allele or the East Asian specific haplotype GCCTA is high in Yunnan, South
      coastal, east coastal of China, and decreased gradually toward inland China,
      West, Northwest and North China. Combined with demographic history in East Asian,
      our results showed that the presence of ALDH2487Lys allele in peripheral regions
      of China might be the results of historical migration events from China to these
      regions. The origin of ALDH2487Lys could be possibly traced back to ancient Pai
      Yuei tribe in South China.

PMID- 19393182
TI  - The complete mitochondrial genome of the cyclopoid copepod Paracyclopina nana: a
      highly divergent genome with novel gene order and atypical gene numbers.
AB  - In this paper, we describe the complete mitogenome of the cyclopoid copepod
      Paracyclopina nana with emphasis on the highly rearranged gene order and high
      divergence against published copepod mitogenomes. The P. nana mtDNA is 15,981 bp
      in length (70.9% AT) and consists of 37 genes (12 protein-coding genes, 2 rRNAs,
      23 tRNAs) that are atypical for metazoan mitogenomes. Unusually, it contains an
      extra tRNA (tRNA-Ala) but it does not contain the ATPase 8 gene. The P. nana
      mitogenome has a long putative control region with high AT content (1351 bp,
      77.0% AT). The Cyt b was considerably short in length, compared to other
      crustaceans. Compared to typical mitogenomes of arthropods and copepods, the gene
      order of the P. nana mitogenome is highly rearranged with a novel gene structure.
      In addition, P. nana has highly divergent mt genes (mostly less than 50%), judged
      by amino acid substitution. We present the first complete mitogenome sequence
      from a cyclopoid copepod, thereby increasing our understanding of copepod and
      crustacean evolution from the mitochondrial point of view.

PMID- 19393180
TI  - Multivariate autoregressive model for a study of phylogenetic diversity.
AB  - We present a computationally effective model to parameterize DNA sequences in a
      way describing comprehensively its auto and cross-correlation structure. The
      approach is based on four-channel Multivariate Autoregressive Model (MVAR). The
      model was applied to a study of genes from the globin family for 6 vertebrate
      species. First, the sequences were coded as four signals (corresponding to the
      nucleotides), which were fitted to a four-channel MVAR. From the correlation
      matrices the vectors of model coefficients were calculated as functions of the
      nucleotide distance. The between-chromosomes and inter-species differences were
      best distinguished in the cross-coefficients binding different nucleotide
      sequences. For clustering purposes different metrics were tested and then two
      clustering procedures (Nearest Neighbor and UPGMA) were applied. The clustering
      trees and consensus trees were constructed for exons, introns and whole genes.
      The results were in agreement with the known dependencies between the chromosomes
      of the globin family. The orthological genes for different species were grouped
      together. Inside these groups the phylogenetically close organisms were localized
      in proximity.

PMID- 19393184
TI  - Regulation of human bone sialoprotein gene transcription by platelet-derived
      growth factor-BB.
AB  - Platelet-derived growth factor (PDGF) is produced by mesenchymal cells and
      released by platelets following aggregation and is synthesized by osteoblasts. In
      bone, PDGF stimulates proliferation and differentiation of osteoblasts. PDGF also
      increases bone resorption, most likely by increasing the number of osteoclasts.
      Bone sialoprotein (BSP) is thought to function in the initial mineralization of
      bone, selectively expressed by differentiated osteoblast. To determine the
      molecular mechanisms PDGF regulation of human BSP gene transcription, we have
      analyzed the effects of PDGF-BB on osteoblast-like Saos2 and ROS17/2.8 cells.
      PDGF-BB (5 ng/ml) increased BSP mRNA and protein levels at 12 h in Saos2 cells,
      and induced BSP mRNA expression at 3 h, reached maximal at 12 h in ROS17/2.8
      cells. Transient transfection analyses were performed using chimeric constructs
      of the human BSP gene promoter linked to a luciferase reporter gene. Treatment of
      Saos2 cells with PDGF-BB (5 ng/ml, 12 h) increased luciferase activities of all
      constructs between -184LUC to -2672LUC including the human BSP gene promoter.
      Effects of PDGF-BB abrogated in constructs included 2 bp mutations in the two
      cAMP response elements (CRE1 and CRE2), activator protein 1(3) (AP1(3)) and shear
      stress response element 1 (SSRE1). Luciferase activities induced by PDGF-BB were
      blocked by protein kinase A inhibitor H89 and tyrosine kinase inhibitor
      herbimycin A. Gel mobility shift analyses showed that PDGF-BB increased binding
      of CRE1, CRE2, AP1(3) and SSRE1 elements. CRE1- and CRE2-protein complexes were
      supershifted by CREB1 and phospho-CREB1 antibodies. Notably, AP1(3)-protein
      complexes were supershifted by c-Fos and JunD, and disrupted by CREB1, phospho
      CREB1, c-Jun and Fra2 antibodies. These studies, therefore, demonstrate that PDGF
      BB stimulates human BSP transcription by targeting the CRE1, CRE2, AP1(3) and
      SSRE1 elements in the human BSP gene promoter.

PMID- 19393185
TI  - High throughput sequencing technology reveals that the taxoid elicitor methyl
      jasmonate regulates microRNA expression in Chinese yew (Taxus chinensis).
AB  - MicroRNAs (miRNAs) are important regulators of gene expression that are
      increasing being implicated in controlling plant development and its interaction
      with the environment. The advent of new high-throughput sequencing technologies
      has enabled both the discovery and quantification of miRNAs from a diverse range
      of species. In this study, we employed high throughput Illumina sequencing to
      identify miRNAs from Taxus chinensis (T. chinensis) cells to investigate the
      effect of the taxoid elicitor methyl jasmonate (MJ) on miRNA expression. In a
      dataset of approximately 6.6 million sequences, a total of 58 miRNAs, belonging
      to 25 families were identified. A majority of them are conserved between
      angiosperms and gymnosperms. However, two miRNAs (miR1310 and miR1314) appear
      gymnosperm-specific, with miR1314 likely to exist as a cluster. MJ treatment
      significantly affected the expression of specific miRNAs; 14 miRNAs from 7
      different families (miR156, miR168, miR169, miR172, miR396, miR480 and mir1310)
      were down regulated whereas 3 miRNAs from 2 families (miR164 and miR390) were up
      regulated.

PMID- 19393186
TI  - Lineage specific evolutionary events on SFTPB gene: Alu recombination-mediated
      deletion (ARMD), exonization, and alternative splicing events.
AB  - SFTPB gene encoding pulmonary surfactant protein has been investigated to have
      transcript variants related with transposable elements (TEs). To investigate the
      alternative splicing event on SFTPB gene, various primate samples (tissue RNA and
      genomic DNA) were used. Two different transcript variants (T1-2 and T2-2) were
      newly identified by RT-PCR analysis. T1-1,-2 and T2-1,-2 are TE-related and
      original transcripts, respectively. T1-1 transcript was investigated to be a lung
      and human specific alternative transcript. T2-1 transcript shows dominant
      expression pattern in lung tissues. T1-related TEs (LTR7B and AluSx) were
      investigated by genomic PCR and sequencing procedure of different primate genomic
      DNAs. Sequencing analysis indicated that they had been integrated into our common
      ancestor genome before the divergence of simian and prosimian and Alu
      recombination-mediated deletion (ARMD) event had been occurred on our common
      ancestor genome after the divergence of New World monkeys and Old World monkeys
      in SFTPB gene 3' UTR region. Taken together, integration event of LTR7B and AluSx
      on SFTPB gene seem to cause lineage specific events via general exonization event
      (New World monkeys and prosimian), ARMD event (Old World monkeys and hominoids),
      and alternative splicing (human) during the primate evolution.

PMID- 19393183
TI  - Development of a cDNA microarray of zebra mussel (Dreissena polymorpha) foot and
      its use in understanding the early stage of underwater adhesion.
AB  - The underwater adhesion of the zebra mussel (Dreissena polymorpha) to substrates
      is a complex process that is controlled by a delicate apparatus, the byssus. As a
      critical activity of the byssus glands embedded in the zebra mussel feet,
      byssogenesis is highly active to produce numerous byssal threads from the settled
      juvenile stage through the adult stage in its life cycle. This lifelong activity
      helps the zebra mussel to firmly attach to substrata underwater, thereby causing
      severe economic and ecologic impacts. In an attempt to better understand the
      zebra mussel's byssus activity, a cDNA microarray (ZMB) including 716 genes,
      generated from a Suppression Subtractive Hybridization (SSH) cDNA library, was
      printed and used for the comparison of gene expression during zebra mussel
      adhesion and non-adhesion. To better understand the byssogenesis mechanism, RNA
      samples from the zebra mussel feet with byssogenesis and without byssogenesis
      were used in a two-color hybridization to reveal the gene differential expression
      in the two states. Based on the P values (P<0.05), Fifty-two ESTs were found as
      differentially expressed genes and were divided into two groups, upregulated and
      downregulated groups according to there logFC values. With the false discovery
      rate (FDR) adjustment, seven were identified from the upregulated group and nine
      from the downregulated group. Phylogenetic analysis indicated that the four
      excretory gland peptide-like protein (EGP) encoding genes in upregulated group
      are structurally different than the two in the downregulated list. The amino acid
      composition analysis on the proteins, which were encoded by the up- or
      downregulated ESTs without homologues (NH) suggested that seven of the NH
      proteins are biochemically similar to the novel foot proteins from other mussels.
      The quantitative reverse transcription PCR (QRT-PCR) proved the uniqueness of the
      templates in the array, and also confirmed the differentially expressed genes
      identified by microarray experiment. Our findings demonstrated that the zebra
      mussel byssus cDNA microarray is an efficient tool for the studies of
      differential gene expression in different byssogenesis states, thereby revealing
      important details of the underwater adhesion.

PMID- 19393187
TI  - Identification and characterization of chicken neuropathy target esterase.
AB  - Neuropathy target esterase (NTE) was proposed as the initial target during the
      process of organophosphate-induced delayed neuropathy (OPIDN) and adult hens are
      the animal model of OPIDN. However, little has been known about the sequence and
      characteristics of chicken NTE. Here, we firstly identified the full length cDNA
      of chicken NTE (cNTE), which contained an open reading frame of 3966 nucleotides
      encoding 1321 amino acids. Chicken NTE had two distinct regions, one was the
      regulatory domain (cNTER) and the other was the catalytic domain (cNEST). Over
      expression of cNTER in mammalian cells did not show any NTE activity, whereas
      cNEST had NTE activity. Cells expressing cNTER tagged with green fluorescent
      protein (GFP) showed accumulation of cNTER-GFP in an endoplasmic reticulum-like
      localization pattern. In addition, macroautophagy and the proteasome pathways
      were found to be involved in the degradation of cNTER, but not cNEST. These
      results first showed that cNTE was an ER-anchored protein and degraded by
      macroautophagy as well as the proteasome.

PMID- 19393189
TI  - Characterization of porcine MMP-2 and its association with immune traits.
AB  - Matrix metalloproteinase-2 (MMP-2) plays important roles in inflammation and
      immunity besides its basic role in degrading and remodelling extracellular matrix
      (ECM). The expression of MMP-2 is up-regulated in many human as well as animal
      models of inflammatory and immune diseases. In this study, we cloned the 5'
      upstream sequence, 3'-downstream sequence as well as other missed genomic
      sequences of porcine MMP-2, the genomic structure and the promotor sequence were
      analyzed and found to share high similarity with those of human MMP-2. Porcine
      MMP-2 was assigned to SSC6p14-p15, and closely linked to microsatellite SW1108
      (53cR, LOD score 7.59) by IMpRH panel. Real-time PCR analysis revealed that the
      expression of porcine MMP-2 was remarkably different in diverse tissues, a high
      level expression was observed in the testis and uterus, relatively low expression
      in other tissues. Allele frequencies determination in different pig breeds and
      association study were performed on the selected SNP and indel. The results
      showed that the SNP AcyI in exon 12 was significantly associated with white blood
      cell count (WBC) of neonate piglets at 0 day (P=0.0079), and classical swine
      fever virus antibody level (CSFV-AB) of pigs at 17 days (P=0.0461), the indel
      MspI in intron 4 had remarkable correlation with mean corpuscular hemoglobin
      (MCH) of pigs at 17 days (P<0.0001).

PMID- 19393188
TI  - TNF induction of jagged-1 in endothelial cells is NFkappaB-dependent.
AB  - TNF-alpha is a potent proinflammatory cytokine that induces endothelial cell (EC)
      adhesion molecules. In addition, TNF promotes angiogenesis by inducing an EC tip
      cell phenotype and the expression of jagged-1, a ligand for the notch pathway.
      Notch signaling is critical for vascular patterning and helps to restrict the
      proliferation of tip cells. Here we demonstrate that TNF induction of jagged-1 in
      human EC is rapid and dependent upon signaling through TNFR1, but not TNFR2. A
      luciferase reporter construct carrying 3.7 kb of 5' promoter sequence from the
      human gene was responsive to both TNF and overexpression of NFkappaB pathway
      components. TNF-induced promoter activation was blocked by treatment with an
      NFkappaB inhibitor or co-expression of dominant-negative IKKbeta. Mutations in a
      putative NFkappaB-binding site at -3.0 kb, which is conserved across multiple
      species, resulted in a loss of responsiveness to TNF and NFkappaB.
      Electromobility shift and chromatin immunoprecipitation assays revealed binding
      of both p50 and p65 to the promoter in response to TNF treatment. Full promoter
      activity also depends on an AP-1 site at -2.0 kb. These results indicate that
      canonical NFkappaB signaling is required for TNF induction of the notch ligand
      jagged-1 in EC.

PMID- 19393190
TI  - The complete mitochondrial genome of the Sichuan Hill Partridge (Arborophila
      rufipectus) and a phylogenetic analysis with related species.
AB  - The complete sequence of the mitochondrial genome of the Sichuan Hill Partridge
      (Arborophila rufipectus) has been determined by long and accurate polymerase
      chain reaction (LA-PCR) and with primer walking sequence method. The genome is
      16728 bp in size, containing 2 ribosomal RNA genes, 13 protein-coding genes, 22
      transfer RNA (tRNA) genes and one control region, demonstrating a structure very
      similar to that of other phasianids. In order to investigate the phylogenetic
      position of Arborophila within Phasianidae, the sequences of 12 concatenated
      heavy-strand encoded protein coding genes were used for phylogenetic analysis
      employing a Bayesian inference method, Maximum parsimony (MP) analyses and
      Maximum likelihood (ML) analysis. With the exception of a few nodes, most
      internal branches were supported by high Bayesian posterior probabilities (BPP)
      and bootstrap probabilities (BSP). Using the 12 mitochondrial protein-coding
      genes sequence, we performed the likelihood tests of competing tree topologies ,
      and also tried to estimate the divergence time within Phasianidae by the global
      rate minimum deformation method (GRMD), both with the previously constructed ML
      tree using Treefinder (Jobb, G., 2008. TREEFINDER version of February 2007.
      Munich(Germany).) The combined strict consensus tree demonstrated that
      Arborophila rufipectus possessed a basal phylogenetic position within
      Phasianidae. Our results also showed that the turkey (Meleagris gallopavo) had a
      close relationship with the gallopheasant group, which may suggest that the
      turkey should be classified into the Phasianidae. In addition, Phasianus was
      found to share a closer relationship with Lophura than Syrmaticus with robust
      support.

PMID- 19393191
TI  - The close relationship between the biosynthetic families of amino acids and the
      organisation of the genetic code.
AB  - By generating random codes and applying Fisher's exact test, we confirm that the
      biosynthetic families of amino acids are intimately involved in the organisation
      of the genetic code. This observation corroborates the coevolution theory of
      genetic code origin. As the amino acids belonging to the single biosynthetic
      families have codons that are contiguous in the genetic code, they must have
      entered the code itself by means of a clustering mechanism, which must clearly
      have been compatible with the mechanism on which this theory is based because
      this too envisages the clustering of biosynthetically correlated amino acids
      within the code.

PMID- 19393192
TI  - Cardiovascular risk in rheumatoid arthritis.
AB  - The increased mortality in rheumatoid arthritis (RA) is mainly due to
      (atherosclerotic) cardiovascular disease. The cardiovascular morbidity is also
      increased in comparison with the general population. This increased
      cardiovascular burden could be caused by 1) an enhanced prevalence of
      cardiovascular risk factors 2) under treatment of cardiovascular risk factors or
      3) RA itself, particularly due to its chronic inflammatory component.
      Cardiovascular risk factors only partially explain the increased cardiovascular
      risk and it is becoming increasingly acknowledged that the underlying
      inflammation in RA plays an essential role. This is probably related to the fact
      that atherosclerosis also has an inflammatory etiology that is accelerated by RA.
      Similarly, it can be expected that effective suppression of this inflammatory
      process by disease modifying antirheumatic drugs and/or biologicals lowers the
      cardiovascular risk. Altogether, there is accumulating evidence that the
      increased cardiovascular risk in RA is comparable to that of type 2 diabetes and
      actually RA should be seen as a new, independent, cardiovascular risk factor for
      which cardiovascular risk management is essential.

PMID- 19393194
TI  - Anti-topoisomerase I autoantibodies in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of
      the skin, vascular abnormalities and activation of the immune system. The
      majority of SSc patients have autoantibodies against nuclear antigens. Among
      these antibodies against topoisomerase I (topo I) are frequently detected in sera
      of SSc patients. Since the discovery of these antibodies as immunoglobulins
      reacting with a 70 kDa nuclear protein (Scl-70), a massive body of clinical and
      experimental data has been generated. In this review we summarize accumulated
      evidence about anti-topo I autoantibodies in SSc, including results of epitope
      mapping studies and investigations on the possible pathogenic role of these
      antibodies.

PMID- 19393193
TI  - Glutathione: a key player in autoimmunity.
AB  - Increasing attention in the physiopathology of inflammatory/immunomediated
      diseases has been focused on the role of reactive oxygen species (ROS), oxygen
      based molecules possessing high chemical reactivity and produced by activated
      neutrophils during the inflammatory response. During chronic inflammation, when
      sustained production of ROS occurs, antioxidant defences can weaken, resulting in
      a situation termed oxidative stress. Moreover, antioxidant defence systems have
      been demonstrated to be constitutively lacking in patients affected with chronic
      degenerative diseases, especially inflammatory/immunomediated. Glutathione, a
      tripeptide, is the principal component of the antioxidant defence system in the
      living cells. Glutathione has been demonstrated to have diverse effects on the
      immune system, either stimulating or inhibiting the immunological response in
      order to control inflammation. The study of interactions between glutathione and
      the immune system has attracted many investigators. Altered glutathione
      concentrations may play an important role in many autoimmune pathological
      conditions prevalently elicited, detrimed and maintained by inflammatory/immune
      response mediated by oxidative stress reactions. The role of glutathione in
      autoimmunity will be reviewed herein.

PMID- 19393195
TI  - Infection and type 1 diabetes mellitus - a two edged sword?
AB  - Infection by various viral and bacterial pathogens has long been proposed as one
      of the etiologies of autoimmune diabetes. Many theories, ranging from direct
      cytolysis of pancreatic islet cells to immunological processes such as antigen
      mimicry and polyclonal lymphocyte activation, tried to explain the
      epidemiological correlation between infections and diabetes, supported by
      information from human and animal studies. However, a direct correlation and
      exact mechanism continue to elude investigators due to scarce and conflicting
      data. Interestingly, there is also data to support an opposite role for infection
      in the development of type 1 diabetes, as several pathogens demonstrated a
      protective effect from this disease. This article reviews the current data
      available from clinical studies and animal models, while trying to explain the
      different mechanisms underlying these findings.

PMID- 19393196
TI  - Autoimmune disease in the era of the metagenome.
AB  - Studies of autoimmune disease have focused on the characteristics of the
      identifiable antibodies. But as our knowledge of the genes associated with the
      disease states expands, we understand that humans must be viewed as
      superorganisms in which a plethora of bacterial genomes - a metagenome - work in
      tandem with our own. The NIH has estimated that 90% of the cells in Homo sapiens
      are microbial and not human in origin. Some of these microbes create metabolites
      that interfere with the expression of genes associated with autoimmune disease.
      Thus, we must re-examine how human gene transcription is affected by the plethora
      of microbial metabolites. We can no longer assume that antibodies generated in
      autoimmune disease are created solely as autoantibodies to human DNA. Evidence is
      now emerging that the human microbiota accumulates during a lifetime, and a
      variety of persistence mechanisms are coming to light. In one model, obstruction
      of VDR nuclear-receptor-transcription prevents the innate immune system from
      making key antimicrobials, allowing the microbes to persist. Genes from these
      microbes must necessarily impact disease progression. Recent efforts to decrease
      this VDR-perverting microbiota in patients with autoimmune disease have resulted
      in reversal of autoimmune processes. As the NIH Human Microbiome Project
      continues to better characterize the human metagenome, new insights into
      autoimmune pathogenesis are beginning to emerge.

PMID- 19393197
TI  - Chronic hepatitis B virus infection in Sjogren's syndrome. Prevalence and
      clinical significance in 603 patients.
AB  - OBJECTIVE: To analyze the prevalence and clinical characteristics of chronic
      hepatitis B virus (HBV) infection in a large series of patients with Sjogren
      syndrome (SS). METHODS: We investigated the prevalence of chronic HBV infection
      in 603 consecutive patients with SS diagnosed in our department between 1994 and
      2008. There were 517 patients with primary SS (482 women and 35 men, with a mean
      age at the time of fulfillment of the classification criteria of 57 years) and 86
      patients with SS associated with chronic HCV infection (66 women and 20 men, with
      a mean age at the time of fulfillment of the classification criteria of 65
      years). All patients fulfilled 4 or more of the 1993 European Community Study
      Group criteria for SS. RESULTS: The presence of HBsAg+ was detected in five
      (0.83%) of the 603 patients with SS. All HBsAg+ patients had primary SS. No
      patient with HCV-related SS had HBV coinfection. There were 4 women and 1 man,
      with a mean age at diagnosis of primary SS of 65 years (range 31 to 89 years).
      All patients showed sicca and systemic involvement. The main extraglandular
      feature was articular involvement in 5 (100%) patients (including arthritis in
      two). The main immunologic features were RF in 4 (80%) patients and ANA in 3
      (60%). No patient had hypocomplementemia, cryoglobulinemia, antimitochondrial or
      anti-LKM1 antibodies. Liver involvement was detected in two patients and
      consisted of slightly raised levels of transaminases. No patient showed clinical
      manifestations of liver disease such as hepatomegaly, splenomegaly, jaundice or
      clinical features of hepatic decompensation (ascites, encephalopathy or
      gastrointestinal bleeding). CONCLUSIONS: We found a prevalence of chronic HBV
      infection of 0.83% in SS, very similar to the prevalence in general population in
      Spain (0.7%). In contrast to the close association between SS and HCV, chronic
      HBV infection is not associated with SS in our geographical area, with a ratio SS
      HBV/SS-HCV cases of 1:10.

PMID- 19393198
TI  - Regulatory T cells in diabetes and gastritis.
AB  - Patients with Type 1 diabetes mellitus (T1D) have an increased prevalence of
      associated organ-specific autoimmune diseases such as pernicious anemia whose
      histological substrate is a chronic atrophic gastritis (CAG). Latent pernicious
      anemia precedes clinically-manifest pernicious anemia and may be difficult to
      detect solely on simple analytical grounds. We recently described an increased
      prevalence of clinically-latent pernicious anemia in T1D using low concentrations
      of pepsinogen I, a zymogen of pepsin present in gastric mucosa, as a useful
      additional diagnostic marker, besides parietal cell antibodies, for screening
      latent pernicious anemia in T1D. The failure of peripheral tolerance mechanisms
      such as regulatory T cells (Treg) might be involved in CAG development in T1D
      patients. Indeed, functional defects in Tregs have been described in T1D
      patients. To this end, the percentage of Tregs in peripheral blood of T1D-CAG
      patients was analyzed and compared with those of a group of T1D without
      associated autoantibodies and a healthy control group. Tregs levels were also
      analyzed in gastric biopsies of T1D-CAG patients. The results obtained have led
      to new questions regarding the pathogenic mechanisms implicated in the
      development of associated autoimmune diseases in T1D.

PMID- 19393199
TI  - Myelin peptides in multiple sclerosis.
AB  - The development of specific therapies for organ-specific autoimmune diseases
      requires the identification of relevant immunogenic epitopes, recognized by both
      pathogenic T cells and autoantibodies. Here, we review the most relevant studies
      focused in the identification of peptides in multiple sclerosis (MS) and the
      distinct T cell reactivity induced in patients compared to controls. Only a few
      studies reported significant differences in terms of T cell reactivity to them.
      The current knowledge on this issue, and the diagnostic and therapeutic
      possibilities opened by the identification of pathogenic MS epitopes are
      discussed in this paper.

PMID- 19393200
TI  - Vitamin D: the alternative hypothesis.
AB  - Early studies on vitamin D showed promise that various forms of the "vitamin" may
      be protective against chronic disease, yet systematic reviews and longer-term
      studies have failed to confirm these findings. A number of studies have suggested
      that patients with autoimmune diagnoses are deficient in 25-hydroxyvitamin D (25
      D) and that consuming greater quantities of vitamin D, which further elevates 25
      D levels, alleviates autoimmune disease symptoms. Some years ago, molecular
      biology identified 25 D as a secosteroid. Secosteroids would typically be
      expected to depress inflammation, which is in line with the reports of
      symptomatic improvement. The simplistic first-order mass-action model used to
      guide the early vitamin studies is now giving way to a more complex description
      of action. When active, the Vitamin D nuclear receptor (VDR) affects
      transcription of at least 913 genes and impacts processes ranging from calcium
      metabolism to expression of key antimicrobial peptides. Additionally, recent
      research on the Human Microbiome shows that bacteria are far more pervasive than
      previously thought, increasing the possibility that autoimmune disease is
      bacterial in origin. Emerging molecular evidence suggests that symptomatic
      improvements among those administered vitamin D is the result of 25-D's ability
      to temper bacterial-induced inflammation by slowing VDR activity. While this
      results in short-term palliation, persistent pathogens that may influence disease
      progression, proliferate over the long-term.

PMID- 19393201
TI  - Latest update on the Ro/SS-A autoantibody system.
AB  - Anti-SS-A (Ro52/Ro60) autoantibodies have been described as serological marker
      for Sjogren's syndrome but are also found in patients with other systemic
      autoimmune diseases. Historically, these autoantibodies were considered as a
      uniform autoantibody-system. However, recent studies provided evidence that Ro60
      and Ro52 are not part of a stable macromolecular complex and that anti-Ro52 and
      anti-Ro60 (SS-A) antibodies have different clinical associations. The prevalence
      of anti-Ro52 in systemic sclerosis and myositis is significantly higher than anti
      Ro60 (SS-A) and isolated anti-Ro52 can be found in up to 37% of myositis
      patients, often correlated with anti-Jo-1 reactivity (p=0.0002). Furthermore,
      recent developments have made significant improvements in the quality of
      recombinant Ro60 showing excellent performance in Ro60 (SS-A) ELISA (Dr. Fooke
      Laboratorien). Of note, single reactivity to either Ro52 or Ro60 (SS-A) can be
      missed when measured with a classical SS-A ELISA based on a mixture of both
      antigens. Approximately 20% of anti-Ro52 or Ro60 (SS-A) positive samples may
      remain undetected using a mixture of both antigens. Moreover, the international
      reference sera from the Centers for Disease Control and Prevention (CDC 2, 3, 7,
      10) were further characterized. It was concluded that Ro60 (SS-A) and Ro52
      represent two distinct autoantibody systems and that separate detection is
      desirable in a clinical diagnostic setting.

PMID- 19393202
TI  - Are autoantibodies triggering endothelial cell apoptosis really pathogenic?
AB  - Anti-endothelial cell (EC) antibodies (AECA) are a heterogeneous group of
      antibodies directed against a variety of EC membrane proteins. A pathogenic role
      for AECA in diseases that involve the vascular system has not been clearly
      demonstrated. Induction of EC apoptosis appears to be one of the mechanisms by
      which AECA may exert their effect. AECA from some patients trigger the
      translocation of anionic phospholipids, most notably phosphatidylserine, from the
      inner to the outer leaflet of the plasma membrane, and thereafter activation of
      caspase 3 and cleavage of poly (ADP-ribose) polymerase, hallmarks of apoptosis.
      Apoptotic cell death generates oxidatively modified moieties, which can induce
      autoimmune and local inflammatory responses. While a sole AECA target involved in
      the apoptotic process of ECs has not been identified, some evidence suggests that
      Heat Shock Proteins may be an outstanding antigen.

PMID- 19393203
TI  - Commercial blot assays in the diagnosis of systemic rheumatic diseases.
AB  - Commercial blot assays are advanced applications of immunoblotting or dot
      immunobinding methodologies for the detection of specific autoantibodies in
      autoimmune diseases. Line(Dot) blots in particular have cost-effectively
      optimized a sort of multiparametric assay for simultaneous determination of
      several autoantibody reactivities. Efficient and wide-spectrum potentialities of
      recombinant DNA technology and proteomics are fruitfully employed by
      manufacturers in order to obtain highly purified antigens or novel targets to be
      spotted on blot matrices thus continuously implementing their multianalytic
      platforms. At present most widely used commercial blot assays for the diagnosis
      of connective tissue diseases can detect autoantibodies to several Extractable
      Nuclear Antigens or myositis and/or scleroderma associated autoantigens. They
      actually represent an important step-forward in the methodological panorama
      designed for the autoimmunity laboratory. However continuous effort in order to
      validate and improve clinical reliability of commercially available blot assays
      should be carried out. In this short review, our preliminary contribution on the
      validation of a commercial line blot assay for the laboratory diagnosis of
      autoimmune myositis is briefly reported.

PMID- 19393204
TI  - B-cell depletion in autoimmune diseases. Advances in autoimmunity.
AB  - B cells play an important role in the pathogenesis of the autoimmune diseases.
      New advances in biological therapy provided a correct way in the management of
      these pathologies. Depletion of B cells with monoclonal antibodies reach an
      important place in the control of the diseases. I will present our experience
      with rituximab in the treatment of 131 patients with different autoimmune
      conditions, and conclude that this kind of therapy is safe, effective and
      constitutes a big step in the control of the majority of patients in which
      humoral response were aberrant. It is one of the many avenues that will allow to
      have a better future in the assessment and treatment of autoimmune diseases.

PMID- 19393205
TI  - Long term treatment of rheumatoid arthritis with rituximab.
AB  - B cells play an important role in the pathogenesis of rheumatoid arthritis (RA).
      Rituximab is a chimeric monoclonal antibody that depletes B-cells by binding to
      the CD20 surface antigen that has been approved for the treatment of RA. Its
      efficacy has been clearly demonstrated by different clinical trials and,
      recently, in long-term observational studies. The use of rituximab in clinical
      practice has highlighted its efficacy and safety over more than 5 years of
      treatment, as well as to try to understand the timing for retreatment of patients
      relapsing after a good initial response.

PMID- 19393206
TI  - The relevance of vitamin D receptor gene polymorphisms for vitamin D research in
      multiple sclerosis.
AB  - A poor vitamin D status has been associated with several autoimmune diseases,
      including multiple sclerosis (MS). The receptor for the biologically active
      metabolite of vitamin D appears to be a key player in these associations, not
      only as a mediator of the biological effects of vitamin D, but also as a mediator
      of the regulation of vitamin D metabolism itself. In this concise review, we will
      discuss the mostly investigated genetic polymorphisms of the vitamin D receptor
      (VDR), and their consequences for VDR functionality and immune regulation. Next,
      we will discuss the association of these polymorphisms with MS, and their
      relation with vitamin D metabolism. We conclude that polymorphisms of the VDR
      have major effects on vitamin D function and metabolism, and should therefore be
      assessed in studies on vitamin D and MS.

PMID- 19393207
TI  - Coxsackievirus infection as an environmental factor in the etiology of type 1
      diabetes.
AB  - Susceptibility to type 1 diabetes (T1D) is dictated by a complex interplay
      between genetic determinants and environmental influences. Accumulating evidence
      strongly supports viral infection as an important factor in the etiology of T1D.
      To this effect, several viruses have been associated with the capacity to induce
      or exacerbate T1D in both humans and mice. The most convincing evidence linking
      viral infection and autoimmunity comes from studies on enteroviruses,
      particularly coxsackievirus. In this review we will discuss the evidence
      associating coxsackievirus infection to T1D and present the current state of
      knowledge on the potential mechanism of coxsackievirus-mediated T1D.

PMID- 19393208
TI  - Proteomic toolbox for autoimmunity research.
AB  - Autoimmune diseases are genetically complex and poorly understood, and may lead
      to clinically severe consequences including end-organ damage. Given this
      scenario, early biomarker discovery is becoming increasingly important for early
      diagnosis and treatment in these diseases. Among the different approaches tried,
      the application of proteomic analysis of body fluids has great potential as a non
      invasive tool for early diagnosis in many different disease settings. During the
      past 10 years, proteomics-based approaches have made steady inroads into the
      study of various autoimmune diseases. In this review, we summarize the highlights
      of various traditional as well as novel proteomic methods, including 2D-MS/MS,
      multi-dimensional HPLC-MS/MS, CE-MS/MS, SELDI-TOF-MS/MS, iTRAQ and a variety of
      targeted antibody-based protein arrays, which have been particularly informative
      in the field of autoimmunity.

PMID- 19393209
TI  - Signaling pathways regulating RAG expression in B lymphocytes.
AB  - Development of B-cell lymphopoiesis is dependent on the presence of recombination
      activating genes RAG1 and RAG2 enzymes. They control the rearrangements of
      immunoglobulin variable, diversity and joining region segments, and allow
      progression of the cellular maturation. RAG1 and RAG2 are successively up- and
      down-regulated at each B-cell stage to progressively generate a B-cell receptor
      for which unforeseeable antigenic specificity results from a stochastic process.
      Therefore, in autoreactive immature B cells, new round of RAG re-expression can
      be observed to eliminate self-reactivity. In some circumstances, RAG up
      regulation can also be found in peripheral mature B lymphocytes, specifically in
      autoimmune diseases. It is therefore of utmost importance to unravel signaling
      pathways that trigger RAG induction in normal and pathological conditions.
      Therapeutic modulation of cytokines or intracellular contacts involved in RAG
      expression might restrict the development of inappropriate autoimmune repertoire.

PMID- 19393210
TI  - Anti-RNA polymerase III antibodies: a marker of systemic sclerosis with rapid
      onset and skin thickening progression.
AB  - Anti-RNA polymerase III antibodies (ARA) are a specific marker for Systemic
      Sclerosis (SSc), associated to severe disease with major organ and diffuse
      cutaneous involvement. In our series, ARA were found in 19 of 216 sera, in 15
      cases as isolated antibodies' specificity, with a statistically negative
      association with other SSc-specific autoantibodies (p: 0.00003). The prevalence
      of ARA among 73 anticentromere and anti-topoisomerase I (topo I) negative sera,
      was 20.5%. Patients with isolated ARA had more rapid disease onset, defined as
      the interval from the appearance of Raynaud's phenomenon to the first symptom
      other than Raynaud's, than patients with isolated anti-topo I antibodies (median:
      2 months vs 13 months; p: 0.0013). A rapid onset of SSc (within 6 months from
      Raynaud's phenomenon onset) was found in all patients with isolated ARA and only
      in 34% of those with anti-topo I (p<0.00001). Moreover, the skin thickening in
      the first months after SSc onset was faster in the ARA group (p<0.0001).
      Nevertheless, the rates of internal organ involvement and of survival rates were
      similar between the two groups. Our experience therefore suggests that ARA are a
      marker of very rapid onset of disease and skin thickening progression in SSc.

PMID- 19393211
TI  - Multiplexing approaches for autoantibody profiling in multiple sclerosis.
AB  - The preliminary positive effects of B cell depletion therapy in multiple
      sclerosis (MS) have renewed interest in a potential role of B cells and
      autoantibodies in the MS disease process. Regardless of a possible pathogenic
      role of the humoral immune response in MS, the analysis of autoantibodies as
      disease markers is valuable. Despite intense research, there is no known MS
      associated antibody specificity that can individually discriminate between MS
      patients and controls. Due to the overlap in autoantibody profiles in autoimmune
      diseases, and due to the complexity of MS, multiplex autoantibody profiling
      approaches are needed to generate a panel of MS-associated autoantibodies with
      high combined sensitivity and specificity for MS. In recent years, several
      multiplexing approaches have been applied in MS autoantibody profiling with
      promising results regarding the generation of a so-called MS-specific
      autoantibody fingerprint. We also recently applied a high-throughput autoantibody
      profiling technique for MS cerebrospinal fluid resulting in the identification of
      a novel panel of 8 antigenic targets with 45% sensitivity and 86% specificity for
      the disease. Identification of MS-specific autoantibody specificities is
      important for the development of diagnostic and prognostic markers for MS.
      Moreover, it can provide more knowledge regarding underlying MS disease processes
      and novel therapeutic targets.

PMID- 19393212
TI  - Autonomic dysfunction in autoimmune rheumatic disease.
AB  - Cardiovascular and neurological manifestations are known to occur in patients
      with autoimmune rheumatic disease (ARD), often in subclinical form. The term
      autonomic nervous system (ANS) describes nerves that are concerned predominantly
      with the regulation of bodily functions. It is comprised of sympathetic and
      parasympathetic nerves, and their function is complementary. ANS involvement has
      rarely been studied in patients with ARD, and studies have shown conflicting
      results. This may be because symptoms of autonomic dysfunction are nonspecific
      and extremely varied, and may pertain to several systems like the
      gastrointestinal, cardiovascular, and nervous. Moreover, tests to detect
      autonomic dysfunction are not routinely employed in clinical rheumatological
      practice. Another difficulty is to differentiate cardiovascular effects of drugs
      from ARD involvement. Previous studies on this topic found signs of
      parasympathetic and sympathetic dysfunction in variable proportions in patients
      with autoimmune diseases, between 24% and 100% in various tests depending on the
      methods used. Cardiovascular autonomic dysfunction is the most common type of ANS
      dysfunction, and was revealed in the majority of ARD patients.

PMID- 19393213
TI  - Oxidized haemoglobin as antigenic target of cell-mediated immune reactions in
      patients with carotid atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease in which immune responses play
      a crucial role. Evidence exist demonstrating the involvement of autoimmune
      mechanisms in atherogenesis. Our aim in this study was to evaluate the possible
      role of human oxidized haemoglobin (Hb) as antigenic target of cell-mediated
      immune reactions in carotid atherosclerosis. PBMC from 44 patients and 24 healthy
      subjects, and T lymphocytes isolated from 9 carotid atherosclerotic plaques were
      tested by cell proliferation assay and by ELISA for cytokine production in
      response to oxidized Hb. This molecule induced a proliferative response in 21 of
      44 (48%) patients' PBMC samples, in 12 of 24 (50%) healthy subjects' PBMC samples
      and in 2 of 9 (22%) infiltrating T lymphocyte samples. Cells from patients
      proliferating in response to oxidized Hb showed high levels of the pro
      inflammatory cytokines interferon (IFN)-gamma and tumor necrosis factor (TNF)
      alpha. Our findings implicate oxidized Hb as a possible antigenic target of cell
      mediated immune responses contributing to inflammation in the pathogenesis of
      carotid atherosclerosis.

PMID- 19393215
TI  - Correcting autoimmune anomalies in autoimmune disorders by immunological means,
      employing the modified vaccination technique.
AB  - Our research group has developed a new vaccination technique in experimental
      animals that has the potential of correcting autoimmune anomalies in humans such
      as autoimmune disorders, cancer, and chronic infections, both prophylactically
      and therapeutically. The vaccination method is called Modified Vaccination
      Technique (MVT). The MVT necessitates the introduction of a purified target
      antigen (ag) and a specific antibody (ab) against the target ag in the form of
      immune complex (IC) to evoke the desired immune response outcome by ab
      information transfer in the injected recipient. The injected IC produces the same
      class of ab in the host, with the same specificity against the target ag, as
      resides in the inoculum. The MVT promises to provide a means of upregulating
      beneficial immune events and downregulating undesirable immune responses in
      individuals, thereby re-establishing normalcy/tolerance to self.

PMID- 19393214
TI  - SOX-1 autoantibodies in patients with paraneoplastic neurological syndromes.
AB  - Paraneoplastic neurological syndromes (PNS) are tumour-associated disorders,
      which are not caused by the tumour itself or its metastases. Since antineuronal
      autoantibodies can be detected in these patients, an autoimmune pathogenesis is
      suspected. Recently, autoantibodies against cerebellar Bergmann glia were found
      in patients with paraneoplastic Lambert-Eaton myasthenic syndrome and other
      paraneoplastic neurological syndromes associated with small cell lung cancer, and
      SOX1 has been identified as the corresponding antigen. SOX1-antibodies have been
      reported to be highly specific for paraneoplastic neurological disorders.
      However, increasing evidence exists that they may also be associated with other
      neuroimmunological disorders without an underlying tumour.

PMID- 19393216
TI  - Elucidation of the disulfide bridge pattern of the recombinant human growth and
      differentiation factor 5 dimer and the interchain Cys/Ala mutant monomer.
AB  - Growth and differentiation factor 5 (GDF5) is involved in many developmental
      processes such as chondrogenesis and joint and bone formation. A recombinant
      monomeric human GDF5 mutant rGDF5(C84A) is in vitro as potent as the dimeric
      native form, and clinical investigations of rGDF5(C84A) are in progress. Native
      homodimeric GDF5 belongs to the transforming growth factor beta (TGF-beta)
      superfamily; each monomer contains a cystine knot formed by three intrachain
      disulfide bridges, and the monomers are connected via an interchain disulfide
      bridge. The disulfide bridge pattern of recombinant homodimeric rGDF5 was
      recently elucidated by X-ray diffraction. A combination of proteolytic
      degradation with thermolysin, separation of the generated fragments by reverse
      phase high-performance liquid chromatography (RP-HPLC), and subsequent analyses
      of the disulfide-linked peptides by electrospray-mass spectrometry and matrix
      assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry, amino acid analysis, and Edman degradation led to the unambiguous
      identification of the disulfide bridge pattern of the monomeric mutant
      rGDF5(C84A) and of the homodimeric rGDF5 in solution. The cystine knot of
      homodimeric rGDF5 exhibits the pattern Cys1-Cys5, Cys2-Cys6, and Cys3-Cys7 (three
      intrachain disulfide bonds), and the monomers are connected by a single
      interchain disulfide bridge (Cys4-Cys4) in accordance with other members of the
      TGF-beta superfamily. The monomeric mutant rGDF5(C84A) exhibits the same cystine
      knot pattern as homodimeric rGDF5.

PMID- 19393217
TI  - Generate Western blot protein marker from a single construct.
AB  - An expression construct, consisting of a tandem arrangement of nucleic acids
      coding for the constant fragments (Fc) receptor of protein G combined with
      nucleic acids for the Fc receptor of protein A, was constructed. When the
      construct was expressed in Escherichia coli, proteins of estimated molecular
      weights of 25, 30, 50, 58, 80, and 85 kDa were consistently obtained from this
      expression construct due to possible proteolytic degradation during the
      cultivation and purification steps. The purified proteins from this single
      expression construct were used as Western blot protein marker.

PMID- 19393218
TI  - Molecular dynamics simulation of water in cytochrome c oxidase reveals two water
      exit pathways and the mechanism of transport.
AB  - We have examined the network of connected internal cavities in cytochrome c
      oxidase along which water produced at the catalytic center is removed from the
      enzyme. Using combination of structural analysis, molecular dynamics simulations,
      and free energy calculations we have identified two exit pathways that connect
      the Mg2+ ion cavity to the outside of the enzyme. Each pathway has a well-defined
      bottleneck, which determines the overall rate of water traffic along the exit
      pathway, and a specific cooperative mechanism of passing it. One of the pathways
      is going via Arg438/439 (in bovine numbering) toward the CuA center, approaching
      closely its His204B ligand and Lys171B residue; and the other is going toward
      Asp364 and Thr294. Comparison of the pathways among different aa3-type enzymes
      shows that they are well conserved. Possible connections of the finding to redox
      coupled proton pumping mechanism are discussed. We propose specific mutations
      near the bottlenecks of the exit pathways that can test some of our hypotheses.

PMID- 19393219
TI  - The amino acid residues of transmembrane helix 5 of multidrug resistance protein
      CaCdr1p of Candida albicans are involved in substrate specificity and drug
      transport.
AB  - In view of the importance of Candida Drug Resistance Protein (Cdr1p) of
      pathogenic Candida albicans in azole resistance, we have characterized its
      ability to efflux variety of substrates by subjecting its entire transmembrane
      segment (TMS) 5 to site directed mutagenesis. All the mutant variants of putative
      21 amino acids of TMS 5 and native CaCdr1p were over expressed as a GFP-tagged
      protein in a heterologous host Saccharomyces cerevisiae. Based on the drug
      susceptibility pattern, the mutant variants could be grouped into two categories.
      The variants belonging to first category were susceptible to all the tested
      drugs, as compared to those belonging to second category which exhibited
      resistance to selective drugs. The mutant variants of both the categories were
      analyzed for their ATP catalysis and drug efflux properties. Irrespective of the
      categories, most of the mutant variants of TMS 5 showed an uncoupling between ATP
      hydrolysis and drug efflux. The mutant variants such as M667A, F673A, I675A and
      P678A were an exception since they reflected a sharp reduction in both K(m) and
      V(max) values of ATPase activity when compared with WT CaCdr1p-GFP. Based on the
      competition experiments, we could identify TMS 5 residues which are specific to
      interact with select drugs. TMS 5 residues of CaCdr1p thus not only impart
      substrate specificity but also selectively act as a communication link between
      ATP hydrolysis and drug transport.

PMID- 19393220
TI  - Conjugated linoleic acid (CLA) prevents age-associated skeletal muscle loss.
AB  - In this study, we examined the effect of CLA isomers in preventing age-associated
      muscle loss and the mechanisms underlying this effect, using 12-months-old
      C57BL/6 mice fed 10% corn oil (CO) or a diet supplemented with 0.5% c9t11-CLA,
      t10c12-CLA, or c9t11-CLA+t10c12-CLA (CLA-mix) for 6months. Both t10c12-CLA and
      CLA-mix groups showed significantly higher muscle mass, as compared to CO and
      c9t11-CLA groups, measured by dual-energy X-ray absorptiometry and muscle wet
      weight. Enhanced mitochondrial ATP production, with higher membrane potential,
      and elevated muscle antioxidant enzymes (catalase and glutathione peroxidase)
      production, accompanied by slight increase in H(2)O(2) production was noted in
      t10c12-CLA and CLA-mix groups, as compared to that of CO and c9t11-CLA groups.
      Oxidative stress, as measured by serum malondialdehyde and inflammation, as
      measured by LPS-treated splenocyte IL-6 and TNF-alpha, were significantly less in
      CLA isomers groups. Thus, CLA may be a novel dietary supplement that will prevent
      sarcopenia by maintaining redox balance during aging.

PMID- 19393221
TI  - yap is required for the development of brain, eyes, and neural crest in
      zebrafish.
AB  - The Yes-associated protein (YAP) is a small protein that binds to many
      transcription factors and modulates their activity. Bioinformatics analysis
      indicated that zebrafish Yap shares high identity with its orthologs in fruit
      fly, chicken, mouse, and human. Expression analysis revealed that maternal
      transcripts of yap are ubiquitous, and endogenous yap is chronologically
      expressed in the notochord, brain, eyes, branchial arches, and pectoral fins.
      Knockdown of yap causes distinct morphological defects in embryos, which display
      a small head with smaller eyes than normal and fewer cartilages in the branchial
      arches. Proneural and neuronal gene expression in yap morphant brain is
      significantly reduced. The expression of crestin is also markedly reduced in all
      recognizable arch-associated regions of yap morphants. Furthermore, TUNEL
      analysis revealed that there is a marked increase in cell death in yap morphant
      brain. In conclusion, zebrafish yap is required for the development of the brain,
      eyes, and neural crest during embryogenesis.

PMID- 19393223
TI  - Muscarinic activation attenuates abnormal processing of beta-amyloid precursor
      protein induced by cobalt chloride-mimetic hypoxia in retinal ganglion cells.
AB  - beta-Amyloid peptide (Abeta), the major pathological factor in Alzheimer's
      disease, has recently been reported to be implicated in the development of
      glaucoma. In this study, we explored the effect of muscarinic activation on
      abnormal processing of beta-amyloid precursor protein (APP) induced by a risk
      factor hypoxia in retinal ganglion cells. Hypoxia mimetic compound cobalt
      chloride could increase the generation of Abeta via up-regulating the expression
      of APP as well as the expression of beta-secretase and gamma-secretase, whereas
      muscarinic receptor agonist pilocarpine could significantly attenuate this
      abnormal pathway, thereby resulting in a decreased amyloidogenic cleavage of APP.
      This finding may provide an insight into better understanding of pathophysiology
      for the retinal neurodegenerative disease and searching for its new modifying
      approach.

PMID- 19393222
TI  - Extravascular inflammation does not increase atherosclerosis in apoE-deficient
      mice.
AB  - There is much speculation whether extravascular inflammation accelerates
      atherosclerosis. We tested this hypothesis in apoE(-/-) mice using three well
      characterized models of non-autoimmune chronic inflammation: croton oil-induced
      skin inflammation, Aspergillus fumigatus antigen-induced allergic lung disease,
      and A. fumigatus antigen-induced peritonitis. The croton oil model produced
      recurrent inflammatory skin ulceration, and marked increases in plasma levels of
      IL-6 and serum amyloid A (SAA). The allergic lung disease model showed strong
      local inflammation with eosinophilic infiltration and serum IgE induction. The
      recurrent peritonitis model was accompanied by mild elevation in plasma SAA
      levels. Aortic atherosclerosis was quantified by computer-assisted morphometry of
      en face arteries in apoE(-/-) mice at 34 weeks for the croton oil model, 26 and
      42 weeks for the allergic lung disease model, and 26 weeks for the peritonitis
      model. We found that all three forms of chronic extravascular inflammation had no
      effect on the rate of atherosclerosis development.

PMID- 19393224
TI  - Down-regulation of mTOR leads to up-regulation of osteoprotegerin in bone marrow
      cells.
AB  - Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor regulates bone mass by
      inhibiting osteoclastic bone resorption. mTOR, which is the mammalian target of
      rapamycin, is a kinase and central regulator of cell growth, proliferation, and
      survival. By using Rapamycin, we studied whether mTOR pathway is associated with
      OPG protein production in the mouse bone marrow-derived stromal cell line ST2.
      Rapamycin markedly increased the level of soluble OPG in ST2 cells. This
      antibiotic treatment resulted in the suppression of phosphorylation of mTOR.
      Rapamycin had no effects on the proliferation, differentiation, or apoptosis of
      the cells. Treatment with bone morphogenetic protein-4, which can induce OPG
      protein in ST2 cells, also resulted in a decrease in the density of the phospho
      mTOR-band, suggesting that the suppression of the phospho-mTOR pathway is
      necessary for OPG production in ST2 cells. Thus, suitable suppression of mTOR
      phosphorylation is a necessary requirement for OPG production in bone marrow
      stromal cells.

PMID- 19393225
TI  - Effect of dose and plasma concentration on liver uptake and pharmacologic
      activity of a 2'-methoxyethyl modified chimeric antisense oligonucleotide
      targeting PTEN.
AB  - The role of dose and plasma concentration on liver tissue uptake and resulting
      antisense pharmacology using a chemically modified antisense oligonucleotide
      (ASO) targeting PTEN was assessed in mice. A single bolus s.c. dose of 60 mg/kg
      in mice showed a time-dependent reduction in liver PTEN mRNA that was maximal at
      48-72 h and returned to near control levels by 20 days after administration.
      These pharmacodynamics are in good agreement with liver concentrations of ASO and
      are consistent with slow elimination (t(1/2)=8 days) of the PTEN ASO from Balb/C
      mouse liver. As expected, highest ASO concentrations in liver resulted from the
      s.c. slow infusion at all doses tested. Unexpectedly, the liver EC(50) for the 24
      h s.c. slow infusion was approximately twofold higher than the two bolus routes
      of administration. Based on plasma concentration analysis it appears that 1-2
      microg/mL ASO plasma concentration is a threshold that, if exceeded, results in
      robust antisense effects and below which there is reduced or complete loss of
      antisense pharmacology in liver even though bulk uptake in the organ is improved.
      Co-administration of a nonsense ASO competed for liver uptake, but unexpectedly
      increased pharmacodynamic response for the active oligonucleotide (ISIS 116847)
      supporting inhibition of a nonproductive bulk uptake pathway while simultaneously
      improving productive uptake (pharmacodynamics). This competition effect was
      similar whether the nonsense oligonucleotide was co-administered with ASO or
      administered up to 24 h prior to active ASO injection.

PMID- 19393226
TI  - Gene expression profiling identifies novel key players involved in the cytotoxic
      effect of Artesunate on pancreatic cancer cells.
AB  - Pancreatic cancer is one of the most aggressive human malignancies, with an
      extremely poor prognosis. The paucity of curative therapies has translated into
      an overall 5-year survival rate of less than 5%, underscoring a desperate need
      for new therapeutic options. Artesunate (ART), clinically used as anti-malarial
      agent, has recently revealed remarkable anti-tumor activity. However, the
      mechanisms underlying those activities in pancreatic cancer are not yet known.
      Here we evaluated the anti-tumor activity of Artesunate and the possible
      underlying mechanisms in pancreatic cancer. MiaPaCa-2 (poorly differentiated) and
      BxPC-3 (moderately differentiated) pancreatic cancer cell lines were treated with
      Artesunate and the effect was monitored by a tetrazolium-based assay (MTS) for
      evaluating cell viability and by flow cytometry and caspase 3/7 activation for
      apoptosis evaluation. In addition cDNA arrays were used to identify
      differentially expressed genes. The microarray data were then validated by RT-PCR
      and Western blotting. Moreover, pathways associated with these expression changes
      were identified using the Ingenuity Pathway Analysis. The expression analysis
      identified a common set of genes that were regulated by Artesunate in pancreatic
      cancer. Our results provide the first in vitro evidence for the therapeutic
      utility of Artesunate in pancreatic cancer. Moreover, we identified Artesunate as
      a novel topoisomerase IIalpha inhibitor that inhibits pancreatic cancer growth
      through modulation of multiple signaling pathways. The present analysis is a
      starting point for the generation of hypotheses on candidate genes and for a more
      detailed dissection of the functional role of individual genes for the activity
      of Artesunate in tumor cells.

PMID- 19393227
TI  - A renaissance in marine pharmacology: from preclinical curiosity to clinical
      reality.
AB  - Marine pharmacology, the pharmacology of marine natural products, has been for
      some time more associated with marine natural products chemistry rather than
      mainstay pharmacology. However, in recent years a renaissance has occurred in
      this area of research, and has seen the US Food & Drug Administration (FDA)
      approval in 2004 of Prialt (ziconotide, omega-conotoxin MVIIA) the synthetic
      equivalent of a conopeptide found in marine snails, used for the management of
      severe chronic pain. Furthermore Yondelis) (trabectedin, ET-743) an antitumor
      agent scovered in a marine colonial tunicate, and now produced synthetically,
      receiving Orphan Drug designation from the European Commission (EC) and FDA for
      soft tissue sarcomas and ovarian cancer and its registration in 2007 in the EU
      for the treatment of soft tissue sarcoma. The approval/marketing of so few marine
      natural products has come after many years of research primarily by the academic
      community and the sporadic involvement of major pharmaceutical companies. This
      commentary, through the opinions provided by several leaders in the marine
      natural products field, will examine the potential reasons and perceptions from
      both the academic and pharmaceutical communities regarding the development of
      marine natural products as viable therapeutic entities.

PMID- 19393228
TI  - Inhibitory effect of 8-(3-chlorostryryl) caffeine on levodopa-induced motor
      fluctuation is associated with intracellular signaling pathway in 6-OHDA-lesioned
      rats.
AB  - 8-(3-chlorostryryl) caffeine (CSC), a selective adenosine A(2A) receptor
      antagonist, has been reported to inhibit the levodopa-induced motor fluctuation
      in Parkinson's disease. However, the underlying mechanism of its action remains
      largely unknown. In our study, we investigated the signaling pathway by which CSC
      inhibited levodopa-induced motor fluctuation in rats with a 6-hydroxydopamine (6
      OHDA)-induced lesion. We treated 6-OHDA-lesioned rats with levodopa (50
      mg/kg/day, twice daily) for 22 days, followed by levodopa+CSC (5 mg/kg/day, twice
      daily) or levodopa+vehicle for 7 days. The sham-lesioned and 6-OHDA-lesioned rats
      treated with saline for 29 days served as sham and lesion control groups. We
      found that the treatment of CSC reversed the shortening of the rotational motor
      response duration induced by levodopa administration and the effect was
      maintained until the end of the treatment. The chronic levodopa treatment
      upregulated the adenosine A(2A) receptor expression and modified downstream
      signaling pathway including decreasing the phosphorylation of DARPP-32 at Thr75
      site and increasing the phosphorylation of ERK1/2 in the lesioned striatum.
      However, the following CSC treatment attenuated the levodopa-induced adenosine
      A(2A) receptor upregulation and abolished the aberrant phosphorylation of DARPP
      32 at Thr75 site and that of ERK1/2. Our results indicate that the inhibitory
      effect of CSC on levodopa-induced motor fluctuation may be associated with the
      inhibition of Adenosine A(2A) Receptor and downstream DARPP-32 and ERK1/2
      signaling pathway.

PMID- 19393230
TI  - No volume difference of medulla oblongata between young and old Korean people.
AB  - The purpose of this study was to determine the effects of aging and gender on the
      volumes of total brain, brainstem, cerebellum and lateral ventricle of healthy
      Koreans by magnetic resonance imaging (MRI). Using three-dimensional MRI
      volumetry, we compared the volumes of various brain regions according to age and
      gender in 115 healthy Koreans. There were significant differences in the volumes
      of midbrain, cerebellum and lateral ventricle, whereas those of brainstem and
      medulla showed no differences between old-age group and young-age group. Men have
      larger volume of medulla than women. Age-related differences in the volumes of
      total brain and pons were significantly larger in men than women.

PMID- 19393229
TI  - Development and aging of the healthy human brain uncinate fasciculus across the
      lifespan using diffusion tensor tractography.
AB  - The human brain uncinate fasciculus (UF) is an important cortico-cortical white
      matter pathway that directly connects the frontal and temporal lobes, although
      there is a lack of conclusive support for its exact functional role. Using
      diffusion tensor tractography, we extracted the UF, calculated its volume and
      normalized it with respect to each subject's intracranial volume (ICV) and
      analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right
      handed children and adults aged 7-68 years. Results showed inverted U-shaped
      curves for fractional anisotropy (FA) with advancing age and U-shaped curves for
      radial and axial diffusivities reflecting white matter progressive and regressive
      myelination and coherence dynamics that continue into young adulthood. The mean
      FA values of the UF were significantly larger on the left side in children
      (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward
      asymmetry (Left>Right) is shown to be due to increased leftward asymmetry in the
      axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial
      diffusivity. This is the first study to provide baseline normative macro and
      microstructural age trajectories of the human UF across the lifespan. Results of
      this study may lend themselves to better understanding of UF role in future
      behavioral and clinical studies.

PMID- 19393231
TI  - Distribution of premotoneurons for jaw-closing and jaw-opening motor nucleus
      receiving contacts from axon terminals of primary somatosensory cortical neurons
      in rats.
AB  - To clarify features of direct projections from the primary somatosensory cortex
      (S1) to premotoneurons for the jaw-closing (JC) and jaw-opening (JO) components
      of the trigeminal motor nucleus, biotinylated dextranamine (BDA) and Fluorogold
      (FG) were used as the anterograde and retrograde tracers. The BDA and FG
      injections were made in the S1 and the JC or JO component, respectively, in rats.
      The distribution of FG-labeled JC and JO premotoneurons receiving contact(s) from
      BDA-labeled axon terminals of S1 neurons was quantitatively examined; the
      contacts were identified microscopically by using a X100 oil immersion objective.
      The largest and second largest numbers of JC and JO premotoneurons with
      contact(s) were found in the lateral reticular formation at the levels of the
      caudal pons and the medulla oblongata (cpmLRt) and trigeminal oral nucleus (Vo)
      bilaterally, and they comprised about 80% of the total premotoneurons with
      contact(s). The percentage of premotoneurons with contact(s) was higher in the Vo
      than in the cpmLRt for both JC and JO premotoneurons. Most of the JC or JO
      premotoneurons found in the nucleus of the solitary tract, inter- and
      supratrigeminal regions, mesencephalic trigeminal nucleus, parabrachial nucleus
      and reticular formation medial to the JO component of the trigeminal motor
      nucleus hardly received contact(s) from S1 neurons. This suggests that the
      contribution of S1 to the control of jaw movements is mediated via JC and JO
      premotoneurons located primarily in the cpmLRt and Vo areas of the brainstem.

PMID- 19393232
TI  - Rapid and reliable genotyping procedure for detection of alleles with mutations,
      deletion, or/and duplication of the CYP2D6 gene.
AB  - BACKGROUND: Polymorphisms of cytochrome P450 2D6 (CYP2D6) have a significant
      effect on the pharmacokinetics of most tricyclic antidepressants. More than 150
      alleles lead to four distinct phenotypes of drug metabolism. The phenotypes are
      described as ultrarapid, extensive, intermediate, and poor metabolizers.
      Therapeutic plasma levels of CYP2D6 substrates may be difficult to achieve. Here
      we describe a rapid and reliable procedure for CYP2D6*4, *3, *6, and *9
      genotyping. DESIGN AND METHODS: Serum concentrations of venlafaxine and its
      pharmacologically active metabolite, O-desmethylvenlafaxine, were measured in
      patients treated with the antidepressant venlafaxine, a substrate of CYP2D6. The
      ODV/V ratio was used as an indicator of the CYP2D6 phenotype, with a higher ratio
      reflecting more rapid metabolism. Real-time PCR with fluorometric melting point
      analysis of the PCR products (LightCycler) is used to identify SNPs. Using
      quantitative PCR, gene deletion and gene duplication or multiplication are
      investigated by measurement of the fluorescence intensity quotient (q, N) of the
      CYP2D6 gene relative to that of the albumin gene as an internal standard.
      RESULTS: Melting curves are verified using DNA samples of known genotypes and by
      sequencing the PCR products. The genotypes and phenotypes that were detected
      correspond to each other. CONCLUSION: A PCR procedure for the detection of CYP2D6
      SNPs, deletions, and duplications is described and is rapid and reliable.

PMID- 19393233
TI  - A synthetic coumarin (4-methyl-7 hydroxy coumarin) has anti-cancer potentials
      against DMBA-induced skin cancer in mice.
AB  - Scopoletin, an alkaloid separated from ethanolic extract of the medicinal plant,
      Gelsemium sempervirens (Fam: Loganiaceae) has been reported to have anti-cancer
      potentials. The synthetic coumarin (4-Methyl-7 hydroxy coumarin) derived from
      resorcinol and ethyl aceto-acetate in presence of concentrated sulphuric acid is
      structurally close to scopoletin, being a coumarin derivative. Whether this
      synthetic compound also has anti-cancer potentials has been evaluated in vivo on
      DMBA (7,12-Dimethylbenz[a]anthracene) induced skin cancer in mice by analyzing
      results of several cytogenetic endpoints, Comet assay, and fluorescence activated
      cell sorting (FACS). Further, expressions of signal proteins like Aryl
      hydrocarbon receptor , p53, PCNA, Akt, Bcl-2, Bcl-xL, Bad, Bax, NF-kappaB Apaf,
      IL-6, Cytochrome-c, Caspase-3 and Caspase-9 were studied by immunoblot analysis
      along with histology of skin and immuno-histochemical localization of Aryl
      hydrocarbon receptor and PCNA in DMBA treated mice vis-a-vis carcinogen treated
      synthetic coumarin fed mice. Feeding of this synthetic coumarin induced positive
      modulations in expression of all biomarkers in DMBA administered mice, giving
      clues on its possible signaling pathway(s) - primarily through down-regulation of
      Aryl hydrocarbon receptor and PCNA and up-regulation of apoptotic proteins like
      Bax, Bad, Cytochrome c, Apaf, Caspase-3 and Caspase-9, resulting in an
      appreciable reduction in growth of papilloma in mice. Therefore, this synthetic
      coumarin shows promise for use in cancer therapy, particularly in skin cancer.

PMID- 19393234
TI  - Interleukin-10 and interferon-gamma up-regulate the expression of B-cell
      activating factor in cultured human promyelocytic leukemia cells.
AB  - B-cell activating factor (BAFF) is a potent cell-survival factor, expressed in
      many hematopoietic cells, for B-cell maturation and activation. It is involved in
      pathogenesis of autoimmune disorders and B-cell malignancies. Although BAFF is
      produced by interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in monocytes,
      the mechanisms of the modulation of BAFF production and expression under normal
      and pathologic conditions have not been completely elucidated. In this study, we
      examined the effects of several inflammatory cytokines on BAFF expression in
      cultured human promyelocytic leukemia (HL-60) cells both at the transcriptional
      and posttranscriptional level. Incubation of the cells with IL-10 and IFN-gamma
      elevated the expression of membrane-bound and soluble forms of BAFF. A similar
      increase in BAFF-specific mRNA was noted in cultured cells. Unexpectedly,
      interleukin-4 (IL-4) treatment hardly affected BAFF expression at the mRNA and
      protein levels. Transcriptional regulation was examined in cultures transfected
      with a human BAFF promoter/reporter gene (chloramphenicol acetyltransferase)
      construct. IL-10 and IFN-gamma elicited marked enhancement of the human BAFF
      promoter activity. Collectively, these results demonstrated that IL-10 and IFN
      gamma both regulate BAFF expression and synthesis in human promyelocytic leukemia
      cell cultures, and the activation occurs at the transcriptional level.

PMID- 19393235
TI  - Tamoxifen inhibits tumor cell invasion and metastasis in mouse melanoma through
      suppression of PKC/MEK/ERK and PKC/PI3K/Akt pathways.
AB  - In melanoma, several signaling pathways are constitutively activated. Among
      these, the protein kinase C (PKC) signaling pathways are activated through
      multiple signal transduction molecules and appear to play major roles in melanoma
      progression. Recently, it has been reported that tamoxifen, an anti-estrogen
      reagent, inhibits PKC signaling in estrogen-negative and estrogen-independent
      cancer cell lines. Thus, we investigated whether tamoxifen inhibited tumor cell
      invasion and metastasis in mouse melanoma cell line B16BL6. Tamoxifen
      significantly inhibited lung metastasis, cell migration, and invasion at
      concentrations that did not show anti-proliferative effects on B16BL6 cells.
      Tamoxifen also inhibited the mRNA expressions and protein activities of matrix
      metalloproteinases (MMPs). Furthermore, tamoxifen suppressed phosphorylated
      extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt through the inhibition
      of PKCalpha and PKCdelta phosphorylation. However, other signal transduction
      factor, such as p38 mitogen-activated protein kinase (p38MAPK) was unaffected.
      The results indicate that tamoxifen suppresses the PKC/mitogen-activated protein
      kinase kinase (MEK)/ERK and PKC/phosphatidylinositol-3 kinase (PI3K)/Akt
      pathways, thereby inhibiting B16BL6 cell migration, invasion, and metastasis.
      Moreover, tamoxifen markedly inhibited not only developing but also clinically
      evident metastasis. These findings suggest that tamoxifen has potential clinical
      applications for the treatment of tumor cell metastasis.

PMID- 19393236
TI  - A 3D analysis of fore- and hindlimb motion during overground and ladder walking:
      comparison of control and unloaded rats.
AB  - During locomotion, muscles are controlled by a network of neurones located in the
      spinal cord and by supraspinal structures. Alterations in that neuromuscular
      system have a functional impact, in particular on locomotion. The hindlimb
      unloading (HU) model in rat has been commonly used to generate disuse since it
      suppresses the hindlimb loading and limits movements. In consequence, it induces
      plastic mechanisms in the muscle, the spinal cord and the sensorimotor cortex.
      The aim of this study was to assess the locomotion in HU rats in two conditions:
      (1) on a runway and (2) in a challenging situation involving the participation of
      supraspinal structures (ladder walking). For that purpose, the motor pattern has
      been investigated by means of 3D motion analysis of the right fore- and hindlimbs
      as well as electromyographic recording of the soleus and tibialis anterior
      muscles. The 3D motion results show that HU induces a support-dependent
      alteration of the kinematics: increased duration of step, stance and swing;
      increased ankle flexion during stance and hyperextension at toe-off; lower
      protraction during swing. The electromyographic results show that whatever the
      support, the flexor and extensor burst duration was longer in HU rats. In
      addition, results show that ladder exacerbates some effects of HU. As ladder
      walking is a situation which requires precision, it is suggested that the control
      of hindlimb movement by supraspinal structures is affected in HU rats.

PMID- 19393237
TI  - Human embryonic stem cell-derived neuronal cells form spontaneously active
      neuronal networks in vitro.
AB  - The production of functional human embryonic stem cell (hESC)-derived neuronal
      cells is critical for the application of hESCs in treating neurodegenerative
      disorders. To study the potential functionality of hESC-derived neurons, we
      cultured and monitored the development of hESC-derived neuronal networks on
      microelectrode arrays. Immunocytochemical studies revealed that these networks
      were positive for the neuronal marker proteins beta-tubulin(III) and microtubule
      associated protein 2 (MAP-2). The hESC-derived neuronal networks were
      spontaneously active and exhibited a multitude of electrical impulse firing
      patterns. Synchronous bursts of electrical activity similar to those reported for
      hippocampal neurons and rodent embryonic stem cell-derived neuronal networks were
      recorded from the differentiated cultures until up to 4 months. The dependence of
      the observed neuronal network activity on sodium ion channels was examined using
      tetrodotoxin (TTX). Antagonists for the glutamate receptors NMDA [D(-)-2-amino-5
      phosphonopentanoic acid] and AMPA/kainate [6-cyano-7-nitroquinoxaline-2,3-dione],
      and for GABAA receptors [(-)-bicuculline methiodide] modulated the spontaneous
      electrical activity, indicating that pharmacologically susceptible neuronal
      networks with functional synapses had been generated. The findings indicate that
      hESC-derived neuronal cells can generate spontaneously active networks with
      synchronous communication in vitro, and are therefore suitable for use in
      developmental and drug screening studies, as well as for regenerative medicine.

PMID- 19393238
TI  - Priming for L-DOPA-induced abnormal involuntary movements increases the severity
      of amphetamine-induced dyskinesia in grafted rats.
AB  - In some patients, graft-induced dyskinesia develops following intrastriatal
      transplantation of embryonic neural tissue for the treatment of Parkinson's
      disease. The mechanisms underlying these involuntary movements need to be
      clarified before this approach to clinical cell therapy can be developed further.
      We previously found that rats with 6-OHDA lesions, primed with L-DOPA treatment
      and that have subsequently undergone intrastriatal graft surgery exhibit
      involuntary movements when subjected to amphetamine. This model of amphetamine
      induced AIMs reflects a pattern of post-graft behaviours that in the absence of
      robust spontaneous GID in the rat is the closest approximation that we currently
      have available. We now show that they are associated with the chronic
      administration of L-DOPA prior to the transplantation surgery. We also
      demonstrate that neither changes in c-fos nor FosB/DeltaFosB expression in the
      lateral striatum are associated with the expression of these behaviours. Taken
      together, these data reveal that the severity of abnormal movements elicited by
      amphetamine in grafted animals may relate to previous L-DOPA exposure and
      dyskinesia development, but they develop through mechanisms that are independent
      of FosB/DeltaFosB upregulation.

PMID- 19393239
TI  - Fasciola gigantica: anthelmintic effect of the aqueous extract of Artocarpus
      lakoocha.
AB  - The effect of the crude extract of Artocarpus lakoocha (70% composition is
      2,4,3',5'- tetrahydroxystilbene -THS) on adult Fasciola gigantica was evaluated
      after incubating the parasites in M-199 medium containing 250, 500, 750 and 1000
      microg/ml of the crude extract, or triclabendazole (TCZ) at the concentrations of
      80 and 175 microg/ml as the positive control, for 3, 6, 12 and 24h, using
      relative motility (RM) assay and observation by scanning electron microscope
      (SEM). Decreased contraction and motility were first observed after 3h incubation
      with TCZ at the concentration 80 and 175 microg/ml. TCZ markedly reduced the
      parasite's motility at the concentration of 175 microg/ml at 6h, and killed the
      worms after 12h exposure. The crude extract of A. lakoocha at all concentrations
      reduced the parasite's motility similar to TCZ at 3h incubation. In 250 and 500
      microg/ml of the crude extract, the values were decreased from 3 to 12h, then
      they were stable between 12 and 24h and reduced to the level approximately 30-40%
      of the control. At 750 and 1000 microg/ml concentrations the crude extract
      rapidly reduced the RM values from the start to 12h and killed the parasites
      between 12 and 24h incubation. The crude extract also inhibited the larval
      migration by 75% and 100% at the concentrations of 250-500 and 750-1000
      microg/ml, respectively. TCZ and the crude extract caused sequentially changes in
      the tegument including swelling, followed by blebbings that later ruptured,
      leading to the erosion and desquamation of the tegument syncytium. As the result,
      lesion was formed which exposed the basal lamina. The damage appeared more severe
      on the dorsal than the ventral surface, and earlier on the anterior part and
      lateral margins when compared to the posterior part. The severity and rapidity of
      the damages were enhanced with increasing concentration of the crude extract.
      Hence, the crude extract of A. lakoocha, may exert its fasciolicidal effect
      against adult F. gigantica by initially causing the tegumental damage.

PMID- 19393240
TI  - Flow cytometric determination of intracellular non-protein thiols in Leishmania
      promastigotes using 5-chloromethyl fluorescein diacetate.
AB  - Leishmania parasites lack catalase and therefore, their anti-oxidant system
      hinges primarily upon non-protein thiols; accordingly, depletion of thiols could
      potentially serve as an effective drug target. We have developed a flow cytometry
      based assay using 5-chloromethyl fluorescein diacetate based upon its selective
      staining of non-protein thiols. Its specificity was confirmed using buthionine
      sulphoximine (a gamma-glutamyl cysteine synthetase inhibitor), diamide (an
      oxidizing agent of intracellular thiols) and N-ethylmaleimide (a covalent
      modifier of cysteine residues) as evidenced by reduction in fluorescence;
      furthermore, restoration of fluorescence by N-acetyl cysteine corroborated
      specificity of 5-chloromethyl fluorescein diacetate to measure non-protein
      thiols. Differences in basal level of thiols in antimony sensitive and antimony
      resistant Leishmania field isolates were detected. The depletion of non-protein
      thiols by conventional anti-leishmanial drugs e.g. antimony and miltefosine was
      demonstrated. Furthermore, fluorescence was unaffected by depletion of ATP in
      majority of the strains studied, indicating that 5-chloromethyl fluorescein
      diacetate is not a substrate for the pump operative in most Leishmania donovani
      strains. Taken together, measurement of 5-chloromethyl fluorescein diacetate
      fluorescence is an effective method for monitoring non-protein thiols in
      Leishmania promastigotes.

PMID- 19393241
TI  - Ornithodoros savignyi: soft tick apyrase belongs to the 5'-nucleotidase family.
AB  - Salivary apyrases are nucleotide-metabolising enzymes that blood-feeding
      parasites utilise for modulation of extracellular nucleotides to prevent platelet
      activation and aggregation. In this study a 5'-nucleotidase specific degenerate
      primer was used to identify homologous transcripts from Ornithodoros savignyi
      salivary gland cDNA. Two 5'-nucleotidase isoforms that share significant sequence
      identity to putative apyrases from Rhipicephalus appendiculatus and Ixodes
      scapularis were identified. Structure prediction showed a tertiary structure
      similar to periplasmic ecto-5'-nucleotidase from Escherichia coli, with high
      conservation of functional residues. The O. savignyi 5'-nucleotidase isoform I
      was recombinantly expressed in Pichia pastoris. Cross-reactivity was demonstrated
      with polyclonal anti-apyrase antisera produced against O. savignyi apyrase.
      Subsequent Edman sequencing and MS/MS analysis of purified O. savignyi apyrase
      identified peptide sequence fragments that shared sequence identity with both
      newly identified 5'-nucleotidase isoforms. It was concluded that wild-type
      apyrase is a mixture of the isoforms identified from the salivary glands of O.
      savignyi. These results represent the first confirmation of a soft (argasid) tick
      apyrase that belongs to the 5'-nucleotidase family of enzymes.

PMID- 19393243
TI  - Structural basis for bivalent Smac-mimetics recognition in the IAP protein
      family.
AB  - XIAP is an apoptotic regulator protein that binds to the effector caspases -3 and
      -7 through its BIR2 domain, and to initiator caspase-9 through its BIR3 domain.
      Molecular docking studies suggested that Smac-DIABLO may antagonize XIAP by
      concurrently targeting both BIR2 and BIR3 domains; on this basis bivalent Smac
      mimetic compounds have been proposed and characterized. Here, we report the X-ray
      crystal structure of XIAP-BIR3 domain in complex with a two-headed compound
      (compound 3) with improved efficacy relative to its monomeric form. A small-angle
      X-ray scattering study of XIAP-BIR2BIR3, together with fluorescence polarization
      binding assays and compound 3 cytotoxicity tests on HL60 leukemia cell line are
      also reported. The crystal structure analysis reveals a network of interactions
      supporting XIAP-BIR3/compound 3 recognition; moreover, analytical gel-filtration
      chromatography shows that compound 3 forms a 1:1 stoichiometric complex with a
      XIAP protein construct containing both BIR2 and BIR3 domains. On the basis of the
      crystal structure and small-angle X-ray scattering, a model of the same BIR2-BIR3
      construct bound to compound 3 is proposed, shedding light on the ability of
      compound 3 to relieve XIAP inhibitory effects on caspase-9 as well as caspases -3
      and -7. A molecular modeling/docking analysis of compound 3 bound to cIAP1-BIR3
      domain is presented, considering that Smac-mimetics have been shown to kill tumor
      cells by inducing cIAP1 and cIAP2 ubiquitination and degradation. Taken together,
      the results reported here provide a rationale for further development of compound
      3 as a lead in the design of dimeric Smac mimetics for cancer treatment.

PMID- 19393242
TI  - Flow cytometric analysis and microsatellite genotyping reveal extensive DNA
      content variation in Trypanosoma cruzi populations and expose contrasts between
      natural and experimental hybrids.
AB  - Trypanosoma cruzi exhibits remarkable genetic heterogeneity. This is evident at
      the nucleotide level but also structurally, in the form of karyotypic variation
      and DNA content differences between strains. Although natural populations of T.
      cruzi are predominantly clonal, hybrid lineages (TcIId and TcIIe) have been
      identified and hybridisation has been demonstrated in vitro, raising the
      possibility that genetic exchange may continue to shape the evolution of this
      pathogen. The mechanism of genetic exchange identified in the laboratory is
      unusual, apparently involving fusion of diploid parents followed by genome
      erosion. We investigated DNA content diversity in natural populations of T. cruzi
      in the context of its genetic subdivisions by using flow cytometric analysis and
      multilocus microsatellite genotyping to determine the relative DNA content and
      estimate the ploidy of 54 cloned isolates. The maximum difference observed was
      47.5% between strain Tu18 cl2 (TcIIb) and strain C8 cl1 (TcI), which we estimated
      to be equivalent to approximately 73 Mb of DNA. Large DNA content differences
      were identified within and between discrete typing units (DTUs). In particular,
      the mean DNA content of TcI strains was significantly less than that for TcII
      strains (P<0.001). Comparisons of hybrid DTUs TcIId/IIe with corresponding
      parental DTUs TcIIb/IIc indicated that natural hybrids are predominantly diploid.
      We also measured the relative DNA content of six in vitro-generated TcI hybrid
      clones and their parents. In contrast to TcIId/IIe hybrid strains these
      experimental hybrids comprised populations of sub-tetraploid organisms with mean
      DNA contents 1.65-1.72 times higher than the parental organisms. The DNA contents
      of both parents and hybrids were shown to be relatively stable after passage
      through a mammalian host, heat shock or nutritional stress. The results are
      discussed in the context of hybridisation mechanisms in both natural and in vitro
      settings.

PMID- 19393245
TI  - NMR structural studies on human p190-A RhoGAPFF1 revealed that domain
      phosphorylation by the PDGF-receptor alpha requires its previous unfolding.
AB  - p190-A and -B Rho GAPs (guanosine triphosphatase activating proteins) are the
      only cytoplasmatic proteins containing FF domains. In p190-A Rho GAP, the region
      containing the FF domains has been implicated in binding to the transcription
      factor TFII-I. Moreover, phosphorylation of Tyr308 within the first FF domain
      inhibits this interaction. Because the structural determinants governing this
      mechanism remain unknown, we sought to solve the structure of the first FF domain
      of p190-A Rho GAP (RhoGAPFF1) and to study the potential impact of
      phosphorylation on the structure. We found that RhoGAPFF1 does not fold with the
      typical (alpha1-alpha2-3(10)-alpha 3) arrangement of other FF domains. Instead,
      the NMR data obtained at 285 K show an alpha1-alpha2-alpha 3-alpha 4 topology. In
      addition, we observed that specific contacts between residues in the first loop
      and the fourth helix are indispensable for the correct folding and stability of
      this domain. The structure also revealed that Tyr308 contributes to the domain
      hydrophobic core. Furthermore, the residues that compose the target motif of the
      platelet-derived growth factor receptor alpha kinase form part of the alpha 3
      helix. We observed that the phosphorylation reaction requires a previous step
      including domain unfolding, a process that occurs at 310 K. In the absence of
      phosphorylation, the temperature-dependent RhoGAPFF1 folding/unfolding process is
      reversible. However, phosphorylation causes an irreversible destabilization of
      the RhoGAPFF1 structure, which probably accounts for the inhibitory effect that
      it exerts on the TFII-I interaction. Our results link the ability of a protein
      domain to be phosphorylated with conformational changes in its three-dimensional
      structure.

PMID- 19393244
TI  - Alternative exon 9-encoded relay domains affect more than one communication
      pathway in the Drosophila myosin head.
AB  - We investigated the biochemical and biophysical properties of one of the four
      alternative regions within the Drosophila myosin catalytic domain: the relay
      domain encoded by exon 9. This domain of the myosin head transmits conformational
      changes in the nucleotide-binding pocket to the converter domain, which is
      crucial to coupling catalytic activity with mechanical movement of the lever arm.
      To study the function of this region, we used chimeric myosins (IFI-9b and EMB
      9a), which were generated by exchange of the exon 9-encoded domains between the
      native embryonic body wall (EMB) and indirect flight muscle isoforms (IFI).
      Kinetic measurements show that exchange of the exon 9-encoded region alters the
      kinetic properties of the myosin S1 head. This is reflected in reduced values for
      ATP-induced actomyosin dissociation rate constant (K(1)k(+2)) and ADP affinity
      (K(AD)), measured for the chimeric constructs IFI-9b and EMB-9a, compared to wild
      type IFI and EMB values. Homology models indicate that, in addition to affecting
      the communication pathway between the nucleotide-binding pocket and the converter
      domain, exchange of the relay domains between IFI and EMB affects the
      communication pathway between the nucleotide-binding pocket and the actin-binding
      site in the lower 50-kDa domain (loop 2). These results suggest an important role
      of the relay domain in the regulation of actomyosin cross-bridge kinetics.

PMID- 19393246
TI  - Knockdown of human COX17 affects assembly and supramolecular organization of
      cytochrome c oxidase.
AB  - Assembly of cytochrome c oxidase, the terminal enzyme of the mitochondrial
      respiratory chain, requires a concerted activity of a number of chaperones and
      factors for the insertion of subunits, accessory proteins, cofactors and
      prosthetic groups. It is now well accepted that the multienzyme complexes of the
      respiratory chain are organized in vivo as supramolecular functional structures,
      so-called supercomplexes. Here, we investigate the role of COX17 in the
      biogenesis of the respiratory chain in HeLa cells. In accordance with its
      predicted function as a copper chaperone and its role in formation of the
      binuclear copper centre of cytochrome c oxidase, COX17 siRNA knockdown affects
      activity and assembly of cytochrome c oxidase. While the abundance of cytochrome
      c oxidase dimers seems to be unaffected, blue native gel electrophoresis reveals
      the disappearance of COX-containing supercomplexes as an early response. We
      observe the accumulation of a novel approximately 150 kDa complex that contains
      Cox1, but not Cox2. This observation may indicate that the absence of Cox17
      interferes with copper delivery to Cox2, but not to Cox1. We suggest that
      supercomplex formation is not simply due to assembly of completely assembled
      complexes. An interdependent assembly scenario for the formation of
      supercomplexes that rather requires the coordinated synthesis and association of
      individual complexes, is proposed.

PMID- 19393247
TI  - Sennoside B inhibits PDGF receptor signaling and cell proliferation induced by
      PDGF-BB in human osteosarcoma cells.
AB  - AIMS: To address the possibility that sennoside B inhibition of cell
      proliferation is mediated via interference with platelet-derived growth factor
      (PDGF) signaling. MAIN METHODS: Human osteosarcoma MG63 cells were treated with
      PDGF in the presence or absence of sennoside B. Activation of the PDGF signaling
      pathway was monitored using western immunoblotting with specific antibodies
      against the PDGF receptor, phosphotyrosine and components of the downstream
      signaling cascade. Activation of cell metabolism and proliferation was assessed
      by chromogenic reduction of MTT. KEY FINDINGS: Sennoside B was found to inhibit
      PDGF-BB-induced phosphorylation of the PDGF receptor (PDGFR) in human MG63
      osteosarcoma cells. Downstream signaling was also affected; pre-incubation of
      PDGF-BB with sennoside B inhibited the phosphorylation of pathway components
      including Ak strain transforming protein (AKT), signal transducer and activator
      of transcription 5 (STAT-5) and extracellular signal-regulated kinase 1/2
      (ERK1/2). Further, we found that sennoside B can bind directly to the
      extracellular domains of both PDGF-BB and the PDGF-beta receptor (PDGFR-beta).
      The effect was specific for sennoside B; other similar compounds including aloe
      emodin, rhein and the meso isomer (sennoside A) failed to inhibit PDGFR
      activation or downstream signaling. Sennoside B also inhibited PDGF-BB
      stimulation of MG63 cell proliferation. SIGNIFICANCE: These results indicate that
      sennoside B can inhibit PDGF-stimulated cell proliferation by binding to PDGF-BB
      and its receptor and by down-regulating the PDGFR-beta signaling pathway.
      Sennoside B is therefore of potential utility in the treatment of proliferative
      diseases in which PDGF signaling plays a central role.

PMID- 19393248
TI  - Genetic polymorphisms in XRCC1, OGG1, APE1 and XRCC3 DNA repair genes, ionizing
      radiation exposure and chromosomal DNA damage in interventional cardiologists.
AB  - Interventional cardiologists working in high-volume cardiac catheterization
      laboratory are exposed to significant occupational radiation risks. Common single
      nucleotide polymorphisms (SNPs) in DNA repair genes are thought to modify the
      effects of low-dose radiation exposure on DNA damage, the main initiating event
      in the development of cancer and hereditary disease. The aim of this study was to
      determine the relationship between XRCC1 (Arg194Trp and Arg399Gln), OGG1
      (Ser326Cys), APE1 (Asp148Glu) and XRCC3 (Thr241Met) SNPs and chromosomal DNA
      damage. We enrolled 77 subjects: 40 interventional cardiologists (27 male, 41.3+/
      9.4 years and 13 female, 37.8+/-8.4 years) and 37 clinical cardiologists (26
      male, 39.4+/-9.5 years and 11 female, 35.0+/-9.8 years) without radiation
      exposure as the control group. Micronucleus (MN) assay was performed as biomarker
      of chromosomal DNA damage and an early predictor of cancer. MN frequency was
      significantly higher in interventional cardiologists than in clinical physicians
      (19.7+/-7.8 per thousand vs. 13.5+/-6.3 per thousand, p=0.0003). Within the
      exposed group, individuals carrying a XRCC3 Met241 allele had higher frequency
      than homozygous XRCC3 Thr241 (21.2+/-7.8 per thousand vs. 16.6+/-7.1 per
      thousand, p=0.03). Individuals with two or more risk alleles showed a higher MN
      frequency when compared to subjects with one or no risk allele (18.4+/-6.6 per
      thousand vs. 14.4+/-6.1 per thousand, p=0.02). An interactive effect was found
      between smoking, exposure >10 years and the presence of the two or more risk
      alleles on the MN frequency (F=6.3, p=0.02). XRCC3 241Met alleles, particularly
      in combination with multiple risk alleles of DNA repair genes, contribute to
      chromosomal DNA damage levels in interventional cardiologists.

PMID- 19393249
TI  - NBN 657del5 heterozygous mutations and colorectal cancer risk in the Czech
      Republic.
AB  - The most frequent Nijmegen breakage syndrome (NBS)-causing mutation is a 5-base
      pair deletion in gene coding for nibrin (NBN 657del5), which results in a non
      fully functional protein product and is particularly frequent in Central and
      Eastern Europe. Recent studies have investigated whether NBN 657del5 carriage may
      predispose to an increased risk of different types of cancer. The Czech Republic
      has one of the highest incidences of colorectal cancer in the world as well as
      high incidence of NBS. To assess whether NBN 657del5 associates with an increased
      risk of sporadic colorectal cancer, we have screened 771 colorectal cancer
      patients, 614 controls with negative colonoscopy and 818 healthy blood donors
      from the Czech Republic. There were no significant differences between the
      frequencies of heterozygous carriers among the three groups. The present results
      do not provide any evidence that the exceeding risk of CRC in this population is
      attributable to the high frequency of heterozygous carriage of the NBN 657del5.

PMID- 19393250
TI  - Proteomic analysis of the nucleus accumbens of rats with different vulnerability
      to cocaine addiction.
AB  - Vulnerability to the addictive effects of drugs of abuse varies among
      individuals, but the biological basis of these differences are poorly known. This
      work tries to increase this knowledge by comparing the brain proteome of animals
      with different rate of extinction of cocaine-seeking behaviour. To achieve this
      goal, we used a place-preference paradigm to separate Sprague Dawley rats in two
      groups: rats that extinguished (E) and rats that did not extinguish (NE) cocaine
      seeking behaviour after a five-day period of drug abstinence. Once the phenotype
      was established, we compared the protein expression in the nucleus accumbens
      (NAC) of these animals after a single injection of either saline (SAL) or cocaine
      (COC, 15 mg/kg). The analysis of protein expression was performed by 2
      dimensional electrophoresis followed by matrix-assisted laser
      desorption/ionization time of flight mass spectrometry. When comparing E SAL and
      NE SAL animals we found significant differences in the expression level of 5
      proteins: ATP synthase subunit alpha, fumarate hydratase, transketolase, NADH
      dehydrogenase [ubiquinone] flavoprotein 2 and glutathione transferase omega-1. A
      single injection of COC differently alters the NAC proteome of E and NE rats;
      thus in E COC animals there was an alteration in the expression of 6 proteins,
      including dihydropyrimidinase-related protein 2 and NADH dehydrogenase
      [ubiquinone] 1 alpha subcomplex subunit 10; whereas in NE COC rats 9 proteins
      were altered (including alpha-synuclein, peroxiredoxin-2 and peroxiredoxin-5).
      These proteins could be potential biomarkers of individual vulnerability to
      cocaine abuse and may be helpful in designing new treatments for cocaine
      addiction.

PMID- 19393251
TI  - BDNF-TrkB signaling pathway mediates the induction of epileptiform activity
      induced by a convulsant drug cyclothiazide.
AB  - Brain-derived neurotrophic factor (BDNF) and its receptor TrkB play an important
      function in neuronal development and synaptic plasticity. Recently we have
      established that cyclothiazide (CTZ) is a novel convulsant drug inducing robust
      epileptiform activity in hippocampal neurons both in vitro and in vivo. However,
      the molecular mechanisms underlying such convulsant action of CTZ are unknown.
      Here, we investigated potential roles of BDNF-TrkB signaling pathway in the CTZ
      induction of epileptiform activity. In anaesthetized rats, CTZ dose-dependently
      induced epileptiform activity characterized by progressing of multiple peaks of
      population spikes, spontaneous spiking events, and synchronized epileptiform
      bursts. Pre-injection of a receptor tyrosine kinase inhibitor K252a or a specific
      antibody for TrkB receptors before intracerebroventricular injection of CTZ
      significantly suppressed the epileptiform activity induced by CTZ. Similarly, in
      cultured hippocampal pyramidal neurons, pre-treatment with CTZ together with
      K252a or TrkB-receptor antibody also inhibited the CTZ-induction of epileptiform
      activity. Furthermore, we demonstrated that acute application of K252a in
      hippocampal cultures inhibited epileptiform bursts and action potential firing.
      We conclude that activation of BDNF-TrkB signaling pathway is fundamentally
      important during the CTZ-induction of epileptiform activity both in vitro and in
      vivo.

PMID- 19393253
TI  - Mechanism of bis(7)-tacrine inhibition of GABA-activated current in cultured rat
      hippocampal neurons.
AB  - Bis(7)-tacrine is a novel dimeric acetylcholinesterase inhibitor derived from
      tacrine that shows promise for the treatment of Alzheimer's disease. We have
      previously reported that bis(7)-tacrine inhibits GABA(A) receptors. In the
      present study we investigated the mechanism of bis(7)-tacrine inhibition of
      GABA(A) receptor function using whole-cell patch-clamp recording in cultured rat
      hippocampal neurons. Bis(7)-tacrine produced a gradual decline of GABA-activated
      current to a steady-state, but this was not an indication of use-dependence, as
      the gradually declining component could be eliminated by exposure to bis(7)
      tacrine prior to GABA application. In addition, bis(7)-tacrine inhibition did not
      require the presence of agonist, and GABA-activated current recovered completely
      from inhibition by bis(7)-tacrine in the absence of agonist. The slow onset of
      inhibition by bis(7)-tacrine was not apparently due to an action at an
      intracellular site, as inclusion of 25 microM bis(7)-tacrine in the recording
      pipette did not alter inhibition by bis(7)-tacrine applied externally. Bis(7)
      tacrine shifted the GABA concentration-response curve to the right in a parallel
      manner and the pA(2) value estimated from a Schild plot was 5.7. Bis(7)-tacrine
      increased the time constant of activation of GABA-gated ion channels without
      affecting the time constants of deactivation or desensitization. These results
      suggest that bis(7)-tacrine is a competitive GABA(A) receptor antagonist with
      slow onset and offset kinetics. The competitive inhibition of GABA receptors by
      bis(7)-tacrine could contribute to its ability to enhance memory.

PMID- 19393252
TI  - Varenicline attenuates nicotine-enhanced brain-stimulation reward by activation
      of alpha4beta2 nicotinic receptors in rats.
AB  - Varenicline, a partial alpha4beta2 and full alpha7 nicotinic receptor agonist,
      has been shown to inhibit nicotine self-administration and nicotine-induced
      increases in extracellular dopamine in the nucleus accumbens. In the present
      study, we investigated whether varenicline inhibits nicotine-enhanced electrical
      brain-stimulation reward (BSR), and if so, which receptor subtypes are involved.
      Systemic administration of nicotine (0.25-1.0 mg/kg, i.p.) or varenicline (0.03-3
      mg/kg, i.p.) produced biphasic effects, with low doses producing enhancement
      (e.g., decreased BSR threshold), and high doses inhibiting BSR. Pretreatment with
      low dose (0.03-1.0 mg/kg) varenicline dose-dependently attenuated nicotine (0.25
      or 0.5 mg/kg)-enhanced BSR. The BSR-enhancing effect produced by varenicline was
      blocked by mecamylamine (a high affinity nicotinic receptor antagonist) or
      dihydro-beta-erythroidine (a relatively selective nicotinic alpha4-containing
      receptor antagonist), but not methyllycaconitine (a selective alpha7 receptor
      antagonist), suggesting an effect mediated by activation of alpha4beta2
      receptors. This suggestion is supported by findings that the alpha4beta2 receptor
      agonist SIB-1765F produced a dose-dependent enhancement of BSR, while
      pretreatment with SIB-1765F attenuated nicotine (0.5 mg/kg)-enhanced BSR. In
      contrast, the selective alpha7 receptor agonist ARR-17779, altered neither BSR
      itself nor nicotine-enhanced BSR, at any dose tested. These findings suggest
      that: 1) varenicline inhibits nicotine-enhanced BSR, supporting its use as a
      smoking cessation aid; and 2) varenicline-enhanced BSR by itself and
      varenicline's anti-nicotine effects are mediated by activation of alpha4beta2,
      but not alpha7, receptors.

PMID- 19393254
TI  - Cortical activity patterns in ADHD during arousal, activation and sustained
      attention.
AB  - OBJECTIVE: The goal of the present study is to test whether there are Attention
      Deficit Hyperactivity Disorder (ADHD)-related differences in brain electrical
      activity patterns across arousal, activation and vigilance states. METHOD: The
      sample consists of 80 adults (38 with ADHD and 42 non-ADHD controls) who were
      recruited for a family study on the genetics of ADHD. Patterns of cortical
      activity were measured using electroencephalography (EEG) during baseline and
      sustained attention conditions and compared according to ADHD diagnostic status.
      Cortical activity was examined separately for the first, middle, and last 5-min
      of the sustained attention task to assess whether patterns differed over time and
      according to ADHD status. RESULTS: In frontal and parietal regions, patterns of
      activation in the alpha (8-10 Hz) range differed according to ADHD status,
      indicating increased cortical arousal among ADHD subjects. Beta power (13-14 and
      17-18 Hz) also differed between ADHD and controls, indicating increased cortical
      activation is associated with ADHD. Behavioral performance on the sustained
      attention task did not differ significantly by diagnosis. EEG correlates of
      cognitive performance differed significantly ADHD diagnosis and were primarily in
      frontal regions. Brain activation patterns recorded during the sustained
      attention task suggest that the ADHD group exhibited significantly increased
      cortical activation at the end of the task when compared to controls.
      CONCLUSIONS: Adults with ADHD may have different neural organization primarily in
      frontal regions which results in the need for continually high levels of cortical
      activation to maintain sustained attention.

PMID- 19393255
TI  - Parallel interhemispheric processing in hemineglect: relation to visual field
      defects.
AB  - Parallel interhemispheric processing is required to explore our visual
      environment and to integrate visual information from both hemifields
      simultaneously. Damage to the right temporo-parietal cortex can disrupt such
      parallel processes and result in neglect and visual extinction of stimuli in the
      left contralesional visual space. Neglected or extinguished stimuli can still be
      processed, yet without reaching the patient's awareness. Such unconscious
      processing has been attributed to structurally intact primary visual areas in
      neglect. To study whether unconscious parallel processing depends on visual
      functional integrity, we compared the performance of neglect patients with visual
      field defects (VFDs) (n=11) and hemianopic patients with partial or complete
      blindness of one visual hemifield (n=11) on redundant targets effects (RTE). The
      RTE manifests as faster reaction times to redundant paired (two stimuli, one in
      each hemifield) than single stimulation (in one hemifield). We found RTEs, i.e.,
      unconscious processing, in neglect patients but not in hemianopic patients.
      Furthermore, neglect patients showed large crossed-uncrossed differences (CUDs),
      i.e., faster response times to ipsi- than contralesional hemifield stimulation,
      reflecting a difference in processing speed for single stimuli in the two
      hemispheres that were correlated with VFDs and visual extinction. The finding
      that extinction, but not RTE, was correlated with the CUD suggests that under
      competitive bilateral stimulus conditions the delayed contralesional visual field
      input may not be detected by the intact left hemisphere, which presumably
      mediates the task given the impairment of the right hemisphere. By contrast,
      unconscious parallel processing of contralesional stimuli (RTE) occurred even
      when contralesional visual field input is lacking (VFD) or delayed (CUD) and is
      possibly mediated via subcortical visual pathways.

PMID- 19393256
TI  - An investigation of the relationship between innovation and cultural diversity.
AB  - In this paper we apply reaction-diffusion models to explore the relationship
      between the rate of behavioural innovation and the level of cultural diversity.
      We investigate how both independent invention and the modification and refinement
      of established innovations impact on cultural dynamics and diversity. Further, we
      analyse these relationships in the presence of biases in cultural learning and
      find that the introduction of new variants typically increases cultural diversity
      substantially in the short term, but may decrease long-term diversity.
      Independent invention generally supports higher levels of cultural diversity than
      refinement. Repeated patterns of innovation through refinement generate
      characteristic oscillating trends in diversity, with increasing trends towards
      greater average diversity observed for medium but not low innovation rates.
      Conformity weakens the relationship between innovation and diversity. The level
      of cultural diversity, and pattern of temporal dynamics, potentially provide
      clues as to the underlying process, which can be used to interpret empirical
      data.

PMID- 19393257
TI  - In utero exposure to chloroquine alters sexual development in the male fetal rat.
AB  - Chloroquine (CQ), a drug that has been used extensively for the prevention and
      treatment of malaria, is currently considered safe for use during pregnancy.
      However, CQ has been shown to disrupt steroid homeostasis in adult rats and
      similar compounds, such as quinacrine, inhibit steroid production in the Leydig
      cell in vitro. To explore the effect of in utero CQ exposure on fetal male sexual
      development, pregnant Sprague-Dawley rats were given a daily dose of either water
      or chloroquine diphosphate from GD 16-18 by oral gavage. Chloroquine was
      administered as 200 mg/kg CQ base on GD 16, followed by two maintenance doses of
      100 mg/kg CQ base on GD 16 and 18. Three days of CQ treatment resulted in reduced
      maternal and fetal weight on GD 19 and increased necrosis and steatosis in the
      maternal liver. Fetal livers also displayed mild lipid accumulation. Maternal
      serum progesterone was increased after CQ administration. Fetal testes
      testosterone, however, was significantly decreased. Examination of the fetal
      testes revealed significant alterations in vascularization and seminiferous
      tubule development after short-term CQ treatment. Anogenital distance was not
      altered. Microarray and RT-PCR showed down-regulation of several genes associated
      with cholesterol transport and steroid synthesis in the fetal testes. This study
      indicates that CQ inhibits testosterone synthesis and normal testis development
      in the rat fetus at human relevant doses.

PMID- 19393258
TI  - Introducing Compsobuthus matthiesseni (Birula, 1905) scorpion as one of the major
      stinging scorpions in Khuzestan, Iran.
AB  - Khuzestan province has the highest rate of scorpion sting in Iran. This is a
      study to identify these scorpions in Khuzestan. In this study 418 scorpions were
      kept in the ethyl alcohol 70%, each being studied by stereomicroscopy and
      diagnosis key separately. 120 (28.7%) Androctonus crassicauda, 104 (24.9%)
      Hemiscorpius lepturus, 91 (21.7%) Mesobuthus eupeus, 86 (20.65%) Compsobuthus
      matthiesseni, 14 (3.35%) Hottentotta saulcyi, 2 (0.5%) Orthochirus scrobiculosus
      and 1 (0.25%) Hottentotta schach were identified. H. lepturus is in the
      Hemiscorpiidae family and the rest are in Buthidae. C. matthiesseni is the most
      frequent and O. scrobiculosus is the least frequent newly identified scorpion.
      This study adds two new sting scorpions to the previous list of 8 identified
      scorpions in Iran.

PMID- 19393259
TI  - The guinea pig as an animal model for Ipomoea carnea induced alpha-mannosidosis.
AB  - The toxic effects of Ipomoea carnea subsp. fistulosa were evaluated in guinea
      pigs by administration of dry leaves during 45 days. Swainsonine and calystegines
      B(1), B(2) and C(1) were isolated and quantified. Clinical signs included
      emaciated and loss of body weight. Histological evaluation demonstrates numerous
      vacuoles in the cytoplasm of pancreas, liver and renal cells. Vacuolation was
      also evident in neurons of brain stem, mainly pontine nuclei. Neuronal lectin
      binding pattern showed a strong positive reaction to Con-A (Concanavalia
      ensiformis), WGA (Triticum vulgaris), sWGA (succinylated T. vulgaris) and LCA
      (Lens culinary). This result is coincident with the lectin histochemistry
      staining pattern of the vacuoles described in CNS of ruminants. We conclude that
      I. carnea subsp. fistulosa induces an intralysosomal accumulation of mannose
      containing oligosaccharides in guinea pigs, which makes it a valuable animal
      model for the reproduction of induced alpha-mannosidosis.

PMID- 19393260
TI  - Cue contrast modulates the effects of exogenous attention on appearance.
AB  - Exogenous spatial attention can be automatically engaged by a cue presented in
      the visual periphery. To investigate the effects of exogenous attention, previous
      studies have generally used highly salient cues that reliably trigger attention.
      However, the cueing threshold of exogenous attention has been unexamined. We
      investigated whether the attentional effect varies with cue salience. We examined
      the magnitude of the attentional effect on apparent contrast [Carrasco, M., Ling,
      S., & Read, S. (2004). Attention alters appearance. Nature Neuroscience, 7(3),
      308-313.] elicited by cues with negative Weber contrast between 6% and 100%. Cue
      contrast modulated the attentional effect, even at cue contrasts above the level
      at which observers can perfectly localize the cue; hence, the result is not due
      to an increase in cue visibility. No attentional effect is observed when the 100%
      contrast cue is presented after the stimuli, ruling out cue bias or sensory
      interaction between cues and stimuli as alternative explanations. A second
      experiment, using the same paradigm with high contrast motion stimuli gave
      similar results, providing further evidence against a sensory interaction
      explanation, as the stimuli and task were defined on a visual dimension
      independent from cue contrast. Although exogenous attention is triggered
      automatically and involuntarily, the attentional effect is gradual.

PMID- 19393261
TI  - Low- and high-level first-order random-dot kinematograms: evidence from fMRI.
AB  - Maximum motion displacement (Dmax) represents the largest dot displacement in a
      random-dot kinematogram (RDK) at which direction of motion can be discriminated.
      Direction discrimination thresholds for maximum motion displacement (Dmax) are
      not fixed but are stimulus dependent. For first-order RDKs, Dmax is larger as dot
      size increases and/or dot density decreases. Dmax may be limited by the receptive
      field size of low-level motion detectors when the dots comprising the RDK are
      small and densely spaced. With RDKs of increased dot size/decreased dot density,
      however, Dmax exceeds the spatial limits of these detectors and is likely
      determined by high-level feature-matching mechanisms. Using functional MRI, we
      obtained greater activation in posterior occipital areas for low-level RDKs and
      greater activation in extra-striate occipital and parietal areas for high-level
      RDKs. This is the first reported neuroimaging evidence supporting proposed low
      level and high-level models of motion processing for first-order random-dot
      stimuli.

PMID- 19393262
TI  - Interaction between human serum esterases and environmental metal compounds.
AB  - Paraoxonase-1 (PON1) and cholinesterase (BChE) are two of the major human serum
      esterases. Although most of variation in PON1 activity results from genetic
      factors, there is growing evidence that environmental chemicals also modulate its
      activity. The aim of this study was to investigate whether environmental exposure
      to metal compounds has any influence on those esterases. A cross-sectional study
      was conducted in a representative sample of the general population of Andalusia,
      South of Spain. PON1 activity against different substrates (paraoxon,
      phenylacetate, diazoxon and dihydrocoumarin) and BChE were measured in serum from
      536 healthy subjects. Potential associations of these esterases with metal
      compounds, age, sex and body mass index as well as life-style habits (smoking,
      alcohol drinking and food habits) were explored. Multiple linear regression
      analysis showed that blood lead levels were significantly associated with
      increased PON1 in serum regardless of the substrate used for the assay. Mercury
      also showed a significant and direct association with PON1 towards paraoxon and
      phenylacetate. In turn, cadmium and zinc levels were significantly associated
      with a decreased PON1 activity (zinc was associated with all PON1 activities and
      cadmium with PON1 towards paraoxon and diazoxon). Arsenic, nickel and manganese
      failed to be significantly associated with any of the PON1 activities assayed.
      PON1 192R alloform predicted significantly higher levels of arsenic and lead.
      BChE, however, was inversely associated with serum levels of manganese and zinc.
      These results suggest that PON1 and BChE activities are modulated by background
      exposure to metal compounds, which may have implications in public health given
      the defensive role played by both enzyme proteins against environmental
      toxicants. The potential underlying mechanisms merit further investigation.

PMID- 19393263
TI  - Neuroinflammation and astrocytic reaction in the course of Phoneutria nigriventer
      (armed-spider) blood-brain barrier (BBB) opening.
AB  - Phoneutria nigriventer spider venom (PNV) causes uneven BBB permeability
      throughout different cerebral regions. Little is known about cellular and
      molecular responses which course with the PNV-induced BBB opening. We investigate
      by immunohistochemistry (IHC) and Western blotting (WB), the GFAP, S100, IFN
      gamma and TNF-alpha proteins expression in hippocampus and cerebellum after
      different time-points from venom or saline intravenous injection. All proteins
      variably altered its expression temporally and regionally. WB showed increased
      GFAP content at 15-45 min followed by a shift below the control level which was
      less pronounced in hippocampus. IHC showed reactive gliosis during all the trial
      period. In cerebellum, GFAP was mostly immunodetected in astrocytes of the
      molecular layer (Bergmann glia), as was S100 protein. The maximum S100
      immunolabeling was achieved at 5h. IFN-gamma and TNF-alpha, expressed mostly by
      hippocampal neurons, increased along the trial period, suggesting a role in BBB
      permeability. In envenomed animals, closer contacts astrocyte-astrocyte, granule
      cells-granule cells and astrocytes-Purkinje cells were observed in cerebellum.
      Closer contacts between neurons-neurons-astrocytes-astrocytes were also seen in
      hippocampus. PNV contains serotonin, histamine, Ca(2+) channels-blocking toxins,
      some of which affect glutamate release. The hypothesis that such substances plus
      the cytokines generated, could have a role in BBB permeability, and that calcium
      homeostasis loss and disturbance of glutamate release are associated with the
      marked GFAP/S100 reaction in Bergmann glia is discussed. The existence of a CNS
      mechanism of defense modulated differentially for fast synthesis and turnover of
      GFAP, S100, IFN-gamma and TNF-alpha proteins was evident. A clear explanation for
      this differential modulation is unclear, but likely result from regional
      differences in astrocytic/neuronal populations, BBB tightness, and/or
      extent/distribution of microvasculature and/or ion channels density/distribution.
      Such differences would respond for transient characteristics of BBB disruption.
      This in vivo model is useful for studies on drug delivery throughout the CNS and
      experimental manipulation of the BBB.

PMID- 19393265
TI  - Depletion of CD8alpha+ lymphocytes attenuates CCL28 expression in villus
      epithelia in rats.
AB  - To examine the involvement of CD8alpha+ intraepithelial lymphocytes (IELs) in
      chemokine expression by villus epithelial cells, villus and crypt fractions were
      collected by mechanical isolation using a chelating buffer and specific
      antibodies in CD8alpha+ cell-depleted rats. A larger population of CD8alpha+
      cells was observed by histochemical evaluation in villus epithelia than in crypt
      epithelia in rat small intestine, and CCL9 and CCL28 expression was higher in the
      crypt fraction than in the villus fraction. The mRNA expression of CCL28 in
      villus fractions isolated from rat small intestinal mucosa was significantly
      reduced compared to that of CCL9, and was accompanied by CD8alpha depletion.
      Using a combined histochemical and flow cytometric approach, CD8alphaalpha+ cells
      were detected in the intraepithelial region of the villus epithelium. Thus, CCL28
      expression in villus epithelial cells is partially supported by CD8alphaalpha+
      cells, and CD8alpha+ IELs are involved in CCL28 expression.

PMID- 19393266
TI  - A biotechnological product and its potential as a new immunomodulator for
      treatment of animal phlebovirus infection: Punta Toro virus.
AB  - Intracellular pathogens with widespread drug-resistance contribute substantially
      to the increasing rates in morbidity and mortality due to emerging and reemerging
      diseases. Thus, the development of new drugs, including those that can enhance
      the immune response, is urgently needed. The immunomodulator, P-MAPA, a
      proteinaceous aggregate of ammonium and magnesium phospholinoleate-palmitoleate
      anhydride derived from Aspergillus oryzae, have been shown to induce antitumor
      activities. The ability of this compound to elicit protective immunity against
      viral infections has not been fully explored. Here, we report findings on the use
      of P-MAPA as an antiviral agent in a mouse model of acute phleboviral (Punta Toro
      virus) disease. A dose administered i.p. 24h post-infectious challenge (100mg/kg
      dose of P-MAPA) was remarkably effective at preventing death due to Punta Toro
      virus infection. This dose also reduced systemic viral burden and liver
      discoloration assayed on day 3 of infection. Taken together, our findings
      indicate that non-specific immunotherapy with P-MAPA appears to be an effective
      treatment for blocking Punta Toro virus-induced disease and suggest that further
      exploration with other viral disease models is warranted.

PMID- 19393267
TI  - Cross interference with TNF-alpha-induced TAK1 activation via EGFR-mediated p38
      phosphorylation of TAK1-binding protein 1.
AB  - Transforming growth factor-alpha-activated kinase 1 (TAK1) has been widely
      recognized as a kinase that regulates multiple intracellular signaling pathways
      evoked by cytokines and immune receptor activation. We have recently reported
      that tumor necrosis factor-alpha (TNF-alpha) triggers internalization of
      epidermal growth factor receptor (EGFR) through a TAK1-p38alpha signaling
      pathway, which results in a transient suppression of the EGFR. In the present
      study, we investigated the pathway of intracellular signaling in the opposite
      direction. Ligand-induced activation of EGFR caused phosphorylation of the TAK1
      binding proteins TAB1 and TAB2 in a TAK1-independent manner. EGFR-mediated
      phosphorylation of TAB1 was completely inhibited by a chemical inhibitor and
      siRNA of p38alpha. The phosphorylation of TAB1 was occurred at Ser-423 and Thr
      431, the residues underlying the p38-mediated feedback inhibition of TAK1. In
      contrast, phosphorylation of TAB2 was sustained, and largely resistant to p38
      inhibition. The inducible phosphorylation of TAB1 interfered with a response of
      EGF-treated cells to TNF-alpha-induced TAK1 activation, which led to the
      reduction of NF-kappaB activation. Collectively, these results demonstrated that
      EGFR activation interfered with TNF-alpha-induced TAK1 activation via p38
      mediated phosphorylation of TAB1.

PMID- 19393268
TI  - alpha-Skeletal muscle actin nemaline myopathy mutants cause cell death in
      cultured muscle cells.
AB  - Nemaline myopathy is a neuromuscular disorder, characterized by muscle weakness
      and hypotonia and is, in 20% of the cases, caused by mutations in the gene
      encoding alpha-skeletal muscle actin, ACTA1. It is a heterogeneous disease with
      various clinical phenotypes and severities. In patients the ultrastructure of
      muscle cells is often disturbed by nemaline rods and it is thought this is the
      cause for muscle weakness. To search for possible defects during muscle cell
      differentiation we expressed alpha-actin mutants in myoblasts and allowed these
      cells to differentiate into myotubes. Surprisingly, we observed two striking new
      phenotypes in differentiating myoblasts: rounding up of cells and bleb formation,
      two features reminiscent of apoptosis. Indeed expression of these mutants induced
      cell death with apoptotic features in muscle cell culture, using AIF and
      endonuclease G, in a caspase-independent but calpain-dependent pathway. This is
      the first report on a common cellular defect induced by NM causing actin mutants,
      independent of their biochemical phenotypes or rod and aggregate formation
      capacity. These data suggest that lack of type II fibers or atrophy observed in
      nemaline myopathy patients may be also due to an increased number of dying muscle
      cells.

PMID- 19393270
TI  - Mucoadhesive effect of thiolated PEG stearate and its modified NLC for ocular
      drug delivery.
AB  - This study was to develop a thiolated non-ionic surfactant, cysteine-polyethylene
      glycol stearate (Cys-PEG-SA), for the assembling of nanoparticulate ocular drug
      delivery system with mucoadhesive property. Cys-PEG-SA was synthesized in two
      steps reaction involving a new derivative intermediate formation of p
      nitrophenylcarbonyl-PEG-SA (pNP-PEG-SA). Up to 369.43+/-25.54 mumol free thiol
      groups per gram of the conjugates was reached. The nanostructured lipid carrier
      (NLC) loaded cyclosporine A (CyA) was prepared by melt-emulsification method. The
      mucoadhesive NLC (Cys-NLC) was obtained by incubating NLC emulsion with Cys-PEG
      SA. The mucoadhesive properties of these nanocarriers were examined by using
      mucin particles method. The particle size or zeta potential of the porcine mucin
      particles were changed with the added concentration of Cys-PEG-SA, and the
      disulphide bond breaker cysteine significantly reduced the adhesion of Cys-NLC to
      mucin particles (P<0.05), whereas PEG-SA and NLC did not alternate the properties
      of the mucin particles. When Cys-NLC was administered topically to the rabbit
      eye, the encapsulated cyclosporine was found to remain on the ocular surface in
      the cul-de-sac for up to 6 h, both precorneal retention time and concentration
      were dramatically increased (P<0.05), compared with the NLC without thiomer
      modification.

PMID- 19393269
TI  - Chewing rescues stress-suppressed hippocampal long-term potentiation via
      activation of histamine H1 receptor.
AB  - We have previously found in rats that chewing, an active behavioral strategy to
      cope with a stressful situation, rescues long-term potentiation (LTP) in the
      hippocampus through activating stress-suppressed N-methyl-D-aspartate (NMDA)
      receptor function. To further examine the mechanisms underlying this ameliorative
      effect of chewing, we studied the involvement of the histaminergic system, which
      has been shown to be activated by mastication, in the LTP of hippocampal slices
      of rats that were allowed to chew a wooden stick during exposure to
      immobilization stress. Chewing failed to rescue stress-suppressed LTP in the rats
      treated with histamine H1 receptor (H1R) antagonist pyrilamine (5 mg/kg, i.p.)
      before exposure to stress, although administration of pyrilamine did not affect
      LTP in naive rats and in stressed rats that did not chew. However, when
      pyrilamine was administrated immediately after exposure to stress, chewing
      rescued LTP whose magnitude was statistically comparable to that in the rats that
      chewed without drug treatment. These results suggest that chewing-induced
      histamine release in the hippocampus and the subsequent H1 receptor activation
      may be essential to rescue stress-suppressed synaptic plasticity.

PMID- 19393271
TI  - Transcriptional regulation of hepatic stellate cells.
AB  - Hepatic stellate cell (HSC) activation is a process of cellular
      transdifferentiation in which, upon liver injury, the quiescent vitamin A storing
      perisinusoidal HSC is converted into a wound-healing myofibroblast and acquires
      potent pro-inflammatory and pro-fibrogenic activities. This remarkable phenotypic
      transformation is underpinned by changes in the expression of a vast number of
      genes. In this review we survey current knowledge of the transcription factors
      that either control HSC activation or which regulate specific fibrogenic
      functions of the activated HSC such as collagen expression, proliferation and
      resistance to apoptosis.

PMID- 19393264
TI  - Drug interactions at the blood-brain barrier: fact or fantasy?
AB  - There is considerable interest in the therapeutic and adverse outcomes of drug
      interactions at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid
      barrier (BCSFB). These include altered efficacy of drugs used in the treatment of
      CNS disorders, such as AIDS dementia and malignant tumors, and enhanced
      neurotoxicity of drugs that normally penetrate poorly into the brain. BBB- and
      BCSFB-mediated interactions are possible because these interfaces are not only
      passive anatomical barriers, but are also dynamic in that they express a variety
      of influx and efflux transporters and drug metabolizing enzymes. Based on studies
      in rodents, it has been widely postulated that efflux transporters play an
      important role at the human BBB in terms of drug delivery. Furthermore, it is
      assumed that chemical inhibition of transporters or their genetic ablation in
      rodents is predictive of the magnitude of interaction to be expected at the human
      BBB. However, studies in humans challenge this well-established paradigm and
      claim that such drug interactions will be lesser in magnitude but yet may be
      clinically significant. This review focuses on current known mechanisms of drug
      interactions at the blood-brain and blood-CSF barriers and the potential impact
      of such interactions in humans. We also explore whether such drug interactions
      can be predicted from preclinical studies. Defining the mechanisms and the impact
      of drug-drug interactions at the BBB is important for improving efficacy of drugs
      used in the treatment of CNS disorders while minimizing their toxicity as well as
      minimizing neurotoxicity of non-CNS drugs.

PMID- 19393272
TI  - Role of MafA in pancreatic beta-cells.
AB  - Pancreatic beta-cell-specific insulin gene expression is regulated by a variety
      of pancreatic transcription factors and the conserved A3, C1 and E1 elements in
      the insulin gene enhancer region are very important for activation of insulin
      gene. Indeed, PDX-1 binding to the A3 element and NeuroD binding to the E1
      element are crucial for insulin gene transcription. Recently, C1 element-binding
      transcription factor was identified as MafA, which is a basic-leucine zipper
      transcription factor and functions as a potent transactivator for the insulin
      gene. Under diabetic conditions, chronic hyperglycemia gradually deteriorates
      pancreatic beta-cell function, which is accompanied by decreased expression
      and/or DNA binding activities of MafA and PDX-1. Furthermore, MafA
      overexpression, together with PDX-1 and NeuroD, markedly induces insulin
      biosynthesis in various non-beta-cells and thereby is a useful tool to
      efficiently induce insulin-producing surrogate beta-cells. These results suggest
      that MafA plays a crucial role in pancreatic beta-cells and could be a novel
      therapeutic target for diabetes.

PMID- 19393273
TI  - Facilitation of zinc influx via AMPA/kainate receptor activation in the
      hippocampus.
AB  - Glutamate and zinc is co-released by excitation of hippocampal mossy fibers and
      both concentrations are increased in the extracellular compartment. In a novel
      environment, however, extracellular zinc is persistently decreased in spite of
      the increase in extracellular glutamate. The mechanism of the decrease in
      extracellular zinc was studied in the present paper. In rats subjected to the
      novelty stress under hippocampal perfusion, the differential changes in
      extracellular glutamate and zinc were abolished in the presence of 1 microM
      tetrodotoxin (TTX), a sodium channel blocker, which reduced exploratory behavior.
      When the hippocampus was perfused with corticosterone (50 ng/ml), extracellular
      zinc was increased. These results suggest that glutamatergic neuron activation
      elicited by novelty stress is involved in the decrease in extracellular zinc and
      that glucocorticoid is not a trigger for its decrease. The differential changes
      in extracellular glutamate and zinc was induced by electrical stimulation to
      analyze the decrease in extracellular zinc; the differential changes were
      elicited by delivery of tetanic stimuli (100 Hz for 1s, 5 min intervals, three
      times) to the hippocampus instead of the novelty stress, as reported previously.
      The changes elicited by tetanic stimulation were abolished in the presence of 10
      microM CNQX, an AMPA/kainate receptor antagonist. In a hippocampal slice double
      labeled with zinc and calcium indicators, furthermore, CNQX inhibited the
      increase in intracellular zinc levels in mossy fiber synapses after delivery of
      tetanic stimuli (100 Hz for 5s) to dentate granule cells. The in vivo and in
      vitro experiments suggest that AMPA/kainate receptor activation is involved in
      zinc influx into hippocampal cells, followed by the decrease in extracellular
      zinc. It is likely that zinc influx is persistently facilitated via stress
      induced glutamatergic neuron activation.

PMID- 19393275
TI  - Inhibitory effect of antidepressants on the NMDA-evoked [(3)H]noradrenaline
      release from rat hippocampal slices.
AB  - We have previously shown that monoamine uptake blocker-type antidepressants with
      different chemical structure and selectivity are able to inhibit neuronal
      nicotinic acetylcholine receptors (nAChRs) in concentrations observed during
      antidepressant treatment. The mechanism of action of these drugs is similar to
      that of mecamylamine, a channel blocker-type antagonist of nAChRs. Since
      mecamylamine has been shown to block also NMDA receptors, our aim was to
      investigate whether the monoamine uptake blockers may affect the function of
      these ionotropic glutamate receptors. We studied, therefore the effect of the two
      most potent nicotinic antagonist antidepressants, the tricyclic desipramine and
      the selective serotonin reuptake inhibitor fluoxetine on the NMDA-induced
      [(3)H]noradrenaline ([(3)H]NA) release from rat hippocampal slices. The NMDA
      induced hippocampal [(3)H]NA release was effectively blocked by the selective,
      non-competitive NMDA antagonist MK-801 (IC(50)=0.54 microM), indicating that the
      [(3)H]NA release was mediated through NMDA receptors. This response was also dose
      dependently inhibited by desipramine (IC(50)=14.57 microM) and fluoxetine
      (IC(50)=41.06 microM). The Na(+)-channel blocker TTX equally inhibited both the
      electrical stimulation- and the NMDA-evoked [(3)H]NA release (the IC(50) was 55
      nM and 66 nM, respectively), whereas the antidepressants inhibited only the NMDA
      evoked response. These data suggest that the inhibitory effect of fluoxetine and
      desipramine on the NMDA-evoked [(3)H]NA release is exerted directly on NMDA
      receptors rather than indirectly on Na(+)-channels. Due to accumulation processes
      the concentration of desipramine and fluoxetine in the brain might be in the same
      range as the observed IC(50) values, thus our data indicate that monoamine uptake
      blocker-type antidepressants are able to influence the function of NMDA receptors
      during antidepressant treatment, and the inhibitory effect on NMDA receptors
      might contribute to the therapeutic effects of these drugs.

PMID- 19393274
TI  - Additive anticonvulsant effects of creatine supplementation and physical exercise
      against pentylenetetrazol-induced seizures.
AB  - Although physical activity and creatine supplementation have been a documented
      beneficial effect on neurological disorders, its implications for epilepsy are
      still controversial. Thus, we decided to investigate the effects of 6 weeks
      swimming training, creatine supplementation (300 mg/kg; p.o.) or its combination
      seizures and neurochemical alterations induced by pentylenetetrazol (PTZ). We
      found that 6 weeks of physical training or creatine supplementation decreased the
      duration of PTZ-induced seizures in adult male Wistar rats, as measured by
      cortical and hippocampal electroencephalography and behavioral analysis.
      Importantly, the combination between physical training and creatine
      supplementation had additive anticonvulsant effects, since it increased the onset
      latency for PTZ-induced seizures and was more effective in decrease seizure
      duration than physical training and creatine supplementation individually.
      Analysis of selected parameters of oxidative stress and antioxidant defenses in
      the hippocampus revealed that physical training, creatine supplementation or its
      combination abrogated the PTZ-elicited increase in levels of thiobarbituric acid
      reactive substances (TBARS) and protein carbonylation, as well as decrease in non
      protein-thiols content, catalase (CAT) and SOD activities. In addition, this
      protocol of physical training and creatine supplementation prevented the PTZ
      induced decrease in hippocampal Na+,K+-ATPase activity. Altogether, these results
      suggest that protection elicited physical training and creatine supplementation
      of selected targets for reactive species-mediated damage decrease of neuronal
      excitability and consequent oxidative damage elicited by PTZ. In conclusion, the
      present study shows that physical training, creatine supplementation or its
      combination attenuated PTZ-induced seizures and oxidative damage in vivo, and
      provide evidence that combination between creatine supplementation and physical
      exercise may be a useful strategy in the treatment of convulsive disorders.

PMID- 19393276
TI  - Mitomycin C-treated antigen-presenting cells as a tool for control of allograft
      rejection and autoimmunity: from bench to bedside.
AB  - Cells have been previously used in experimental models for tolerance induction in
      organ transplantation and autoimmune diseases. One problem with the therapeutic
      use of cells is standardization of their preparation. We discuss an
      immunosuppressive strategy relying on cells irreversibly transformed by a
      chemotherapeutic drug. Dendritic cells (DCs) of transplant donors pretreated with
      mitomycin C (MMC) strongly prolonged rat heart allograft survival when injected
      into recipients before transplantation. Likewise, MMC-DCs loaded with myelin
      basic protein suppressed autoreactive T cells of MS patients in vitro and
      prevented experimental autoimmune encephalitis in mice. Comprehensive gene
      microarray analysis identified genes that possibly make up the suppressive
      phenotype, comprising glucocorticoid leucine zipper, immunoglobulin-like
      transcript 3, CD80, CD83, CD86, and apoptotic genes. Based on these findings, a
      hypothetical model of tolerance induction by MMC-treated DCs is delineated.
      Finally, we describe the first clinical application of MMC-treated monocyte
      enriched donor cells in an attempt to control the rejection of a haploidentical
      stem cell transplant in a sensitized recipient and discuss the pros and cons of
      using MMC-treated antigen-presenting cells for tolerance induction. Although many
      questions remain, MMC-treated cells are a promising clinical tool for controlling
      allograft rejection and deleterious immune responses in autoimmune diseases.

PMID- 19393278
TI  - A tiered approach to the use of alternatives to animal testing for the safety
      assessment of cosmetics: skin irritation.
AB  - Evaluation of the skin irritancy and corrosivity potential of an ingredient is a
      necessity in the safety assessment of cosmetic ingredients. To date, there are
      two formally validated alternatives to the rabbit Draize test for skin
      corrosivity in place, namely the rat skin transcutaneous electrical resistance
      (TER) assay and the Human Skin Model Test using EpiSkin, EpiDerm and SkinEthic
      reconstructed human epidermal equivalents. For skin irritation, EpiSkin, EpiDerm
      and SkinEthic are validated as stand-alone test replacements for the rabbit
      Draize test. Data from these tests are rarely considered in isolation and are
      evaluated in combination with other factors to establish the overall irritating
      or corrosive potential of an ingredient. In light of the deadlines established in
      the Cosmetics Directive for cessation of animal testing for cosmetic ingredients,
      a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review
      the use of alternative approaches and to set up a decision tree approach for
      their integration into tiered testing strategies for hazard and safety assessment
      of cosmetic ingredients and their use in products. In conclusion, the safety
      assessments for skin irritation/corrosion of new chemicals for use in cosmetics
      can be confidently accomplished using exclusively alternative methods.

PMID- 19393279
TI  - A tiered approach to the use of alternatives to animal testing for the safety
      assessment of cosmetics: eye irritation.
AB  - The need for alternative approaches to replace the in vivo rabbit Draize eye test
      for evaluation of eye irritation of cosmetic ingredients has been recognised by
      the cosmetics industry for many years. Extensive research has lead to the
      development of several assays, some of which have undergone formal validation.
      Even though, to date, no single in vitro assay has been validated as a full
      replacement for the rabbit Draize eye test, organotypic assays are accepted for
      specific and limited regulatory purposes. Although not formally validated,
      several other in vitro models have been used for over a decade by the cosmetics
      industry as valuable tools in a weight of evidence approach for the safety
      assessment of ingredients and finished products. In light of the deadlines
      established in the EU Cosmetics Directive for cessation of animal testing for
      cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th
      January, 2008 to review the use of alternative approaches and to set up a
      decision-tree approach for their integration into tiered testing strategies for
      hazard and safety assessment of cosmetic ingredients and their use in products.
      Furthermore, recommendations are given on how remaining data gaps and research
      needs can be addressed.

PMID- 19393280
TI  - The relationship between the IC(50), toxic threshold, and the magnitude of
      stimulatory response in biphasic (hormetic) dose-responses.
AB  - Hormesis is a dose-response relationship characterized by a biphasic (U- or
      inverted U-shaped) response. We present the results of a study designed to assess
      the relationship between toxic potency (as measured by the IC(50)) and the
      magnitude of the hormesis stimulation. To facilitate this, we describe a new
      parameter (Delta(X)), which we define as the difference between the concentration
      (or dose) that inhibits 50% of the growth of the organism under study (IC(50)),
      and the concentration (or dose) of the respective toxicological threshold (either
      the benchmark dose (BMD) or zero equivalent point (ZEP)). Our analysis includes a
      subset of data from a previously published report describing a National Cancer
      Institute study that exposed yeast to putative anticancer agents in a high
      throughput assay. The toxic threshold used in this paper was the BMD(5). Thus,
      the Delta(X) in this paper is defined as: Delta(X)=IC(50)-BMD(5). We have found
      that the Delta(X) and the magnitude of stimulation above the control response are
      inversely related. These findings describe the first known relationship between
      toxic potency and the magnitude of hormetic response and warrant further inquiry.

PMID- 19393282
TI  - Roles for the subiculum in spatial information processing, memory, motivation and
      the temporal control of behaviour.
AB  - The subiculum is in a pivotal position governing the output of the hippocampal
      formation. Despite this, it is a rather under-explored and sometimes ignored
      structure. Here, we discuss recent data indicating that the subiculum
      participates in a wide range of neurocognitive functions and processes. Some of
      the functions of subiculum are relatively well-known-these include providing a
      relatively coarse representation of space and participating in, and supporting
      certain aspects of, memory (particularly in the dynamic bridging of temporal
      intervals). The subiculum also participates in a wide variety of other
      neurocognitive functions too, however. Much less well-known are roles for the
      subiculum, and particularly the ventral subiculum, in the response to fear,
      stress and anxiety, and in the generation of motivated behaviour (particularly
      the behaviour that underlies drug addiction and the response to reward). There is
      an emerging suggestion that the subiculum participates in the temporal control of
      behaviour. It is notable that these latter findings have emerged from a
      consideration of instrumental behaviour using operant techniques; it may well be
      the case that the use of the watermaze or similar spatial tasks to assess
      subicular function (on the presumption that its functions are very similar to the
      hippocampus proper) has obscured rather than revealed neurocognitive functions of
      subiculum. The anatomy of subiculum suggests it participates in a rather subtle
      fashion in a very broad range of functions, rather than in a relatively more
      isolated fashion in a narrower range of functions, as might be the case for
      "earlier" components of hippocampal circuitry, such as the CA1 and CA3 subfields.
      Overall, there appears to a strong dorso-ventral segregation of function within
      subiculum, with the dorsal subiculum relatively more concerned with space and
      memory, and the ventral hippocampus concerned with stress, anxiety and reward.
      Finally, it may be the case that the whole subiculum participates in the temporal
      control of reinforced behaviour, although further experimentation is required to
      clarify this hypothesis.

PMID- 19393281
TI  - Relative absorption and dermal loading of chemical substances: Consequences for
      risk assessment.
AB  - Quantification of skin absorption is an essential step in reducing the
      uncertainty of dermal risk assessment. Data from literature indicate that the
      relative dermal absorption of substances is dependent on dermal loading.
      Therefore, an internal exposure calculated with absorption data determined at a
      dermal loading not comparable to the actual loading may lead to a wrong
      assessment of the actual health risk. To investigate the relationship between
      dermal loading and relative absorption in a quantitative manner, 138 dermal
      publicly available absorption experiments with 98 substances were evaluated (87
      in vitro, 51 in vivo; molecular weight between 40 and 950, logP between -5 and
      13), with dermal loading ranging mostly between 0.001 and 10mg/cm(2). In 87
      experiments (63%) an inverse relationship was observed between relative dermal
      absorption and dermal loading, with an average decrease of factor 33+/-69. Known
      skin irritating and volatile substances less frequently showed an inverse
      relationship between dermal loading and relative absorption.

PMID- 19393283
TI  - Induction of apoptosis by phloroglucinol derivative from Ecklonia Cava in MCF-7
      human breast cancer cells.
AB  - Phloroglucinol derivatives, dioxinodehydroeckol (1) and 1-(3',5'
      dihydroxyphenoxy)-7-(2'',4'',6-trihydroxyphenoxy)-2,4,9-trihydroxydibenzo-1,4
      dioxin (2), were isolated from Ecklonia Cava. Their ability to inhibit the
      proliferation of human breast cancer cells were evaluated by measuring cell death
      via induction of apoptosis. Compound 1 exerted a higher anti-proliferative
      activity in human breast cancer cells compared with compound 2. Furthermore,
      compound 1 induced a significant proliferative inhibition and apoptosis in a dose
      dependent manner on MCF-7 human cancer cells. Treatment with compound 1 also
      induced the increase in caspase (-3 and -9) activity, DNA repair enzyme poly-(ADP
      ribose) polymerase (PARP) cleavage, and pro-apoptotic gene and the decrease in
      anti-apoptotic gene. In addition, NF-kappaB family and -dependent activated genes
      were down-regulated by compound 1. These results indicated that the potential
      inhibitory effect of compound 1 against growth of MCF-7 human breast cancer cells
      might be associated with induction of apoptosis through NF-kappaB family and NF
      kappaB dependent pathway. The present results suggest that compound 1 has a
      promising potential to be used as a valuable chemopreventive agent.

PMID- 19393284
TI  - Induction of apoptosis and inhibition of telomerase activity in human lung
      carcinoma cells by the water extract of Cordyceps militaris.
AB  - Cordyceps militaris is well known as a traditional medicinal mushroom and is a
      potentially interesting candidate for use in cancer treatment. In this study, the
      potential of the water extract of C. militaris (WECM) to induce apoptosis in
      human lung carcinoma A549 cells and its effects on telomerase activity were
      investigated. The growth inhibition and apoptosis induction by WECM treatment in
      A549 cells was associated with the induction of Fas, catalytic activation of
      caspase-8, and Bid cleavage. Activation of caspases, downregulation of anti
      apoptotic Bcl-2 expression, and upregulation of pro-apoptotic Bax protein were
      also observed in WECM-treated cells. However, the cytotoxic effects and apoptotic
      characteristics induced by WECM were significantly inhibited by z-DEVD-fmk, a
      caspase-3 inhibitor, which demonstrates the important role that caspase-3 plays
      in the process. In addition, WECM exerted a dose-dependent inhibition of
      telomerase activity via downregulation of human telomerase reverse transcriptase
      (hTERT), c-myc and Sp1 expression. Taken together, the data from this study
      indicate that WECM induces the apoptosis of A549 cells through a signaling
      cascade of death receptor-mediated extrinsic and mitochondria-mediated intrinsic
      caspase pathways. It was also conclude that apoptotic events due to WECM were
      mediated with diminished telomerase activity through the inhibition of hTERT
      transcriptional activity.

PMID- 19393285
TI  - Systems genetics analysis of iron regulation in the brain.
AB  - Iron imbalances in the brain, including excess accumulation and deficiency, are
      associated with neurological disease and dysfunction; yet, their origins are
      poorly understood. Using systems genetics analysis, we have learned that large
      individual differences exist in brain iron concentrations, even in the absence of
      neurological disease. Much of the individual differences can be tied to the
      genetic makeup of the individual. This genetic-based differential regulation can
      be modeled in genetic reference populations of rodents. The work in our
      laboratory centers on iron regulation in the brain and our animal model consists
      of 25 BXD/Ty recombinant inbred mouse strains. By studying naturally occurring
      variation in iron phenotypes, such as tissue iron concentration, we can tie that
      variability to one or more genes by way of quantitative trait loci (QTL)
      analysis. Moreover, we can conduct genetic correlation analyses between our
      phenotypes and others previously measured in the BXD/Ty strains. We have observed
      several suggestive QTL related to ventral midbrain iron content, including one on
      chromosome 17 that contains btbd9, a gene that in humans has been associated with
      restless legs syndrome and serum ferritin. We have also observed gene expression
      correlations with ventral midbrain iron, including btbd9 expression and dopamine
      receptor expression. In addition, we have observed significant correlations
      between ventral midbrain iron content and dopamine-related phenotypes. The
      following is a discussion of iron regulation in the brain and the contributions a
      systems genetics approach can make toward understanding the genetic underpinnings
      and relation to neurological disease.

PMID- 19393286
TI  - Expression, purification, and characterization of the intra-cellular domain of
      the ANP receptor.
AB  - The membrane-bound atrial natriuretic peptide receptor (GCA) catalyzes the
      formation of cGMP from GTP in response to natriuretic peptide hormones. Previous
      structural studies have focused on the extra-cellular hormone binding domain of
      this receptor whereas its intra-cellular domain has not yet been amenable to such
      studies. We report here the baculovirus expression and purification of the GCA
      intra-cellular domain construct GCA(ID) comprising the complete intra-cellular
      region which includes the kinase-homology domain, coiled-coil region, and
      catalytic cyclase domain. The intra-cellular domain was enzymatically
      characterized in terms of guanylyl cyclase activity and the effects of ATP,
      manganese, and Triton X-100. Our results indicate that the activity of the intra
      cellular domain of the ANP receptor is about 2 fold less active compared to a
      truncated cyclase domain construct lacking the kinase-like domain that was also
      expressed and purified. In addition, unlike the full length receptor, the intra
      cellular domain could not be activated by Triton X-100/Mn(2+) or its activity
      stimulated by ATP. These data therefore indicate that the major part of the
      transition from the basal state to the fully, ANP/ATP-dependent, activated state
      as well its stimulation/enhancement by Triton X-100/Mn(2+) requires the full
      length receptor. These receptor insights could aid in the development of novel
      therapeutics as the GCA receptor is a key drug target for cardiovascular
      diseases.

PMID- 19393287
TI  - SELDI-TOF MS detection of urinary hepcidin.
AB  - Hepcidin is a 25-residue hepatic peptide that regulates iron absorption from the
      diet and tissue iron distribution. Inappropriately low Hepcidin expression is
      implicated in the pathogenesis of hereditary hemochromatosis and iron-loading
      anemias, like the thalassemias. Increased hepcidin expression mediates iron
      retention in the anemias of inflammation and plays a pathogenic role in iron
      refractory iron-deficiency anemia (IRIDA). Because of its clinical importance,
      Hepcidin is expected to be a useful biomarker for diagnosis and management of
      iron-related disorders. So far an ELISA for human hepcidin and SELDI-TOF-MS based
      approaches have been applied to monitor urinary and/or serum hepcidin levels.
      Here we report a modified protocol for SELDI-TOF based detection of human,
      urinary hepcidin. We show that CM10 Proteinchips are superior to NP20
      Proteinchips commonly used in previously reported protocols to sensitively and
      accurately detect urinary hepcidin. Application of this modified hepcidin assay
      accurately detects increased hepcidin levels in the urine of sepsis patients.

PMID- 19393288
TI  - Stress-induced analgesia.
AB  - For over 30 years, scientists have been investigating the phenomenon of pain
      suppression upon exposure to unconditioned or conditioned stressful stimuli,
      commonly known as stress-induced analgesia. These studies have revealed that
      individual sensitivity to stress-induced analgesia can vary greatly and that this
      sensitivity is coupled to many different phenotypes including the degree of
      opioid sensitivity and startle response. Furthermore, stress-induced analgesia is
      influenced by age, gender, and prior experience to stressful, painful, or other
      environmental stimuli. Stress-induced analgesia is mediated by activation of the
      descending inhibitory pain pathway. Pharmacological and neurochemical studies
      have demonstrated involvement of a large number of neurotransmitters and
      neuropeptides. In particular, there are key roles for the endogenous opioid,
      monoamine, cannabinoid, gamma-aminobutyric acid and glutamate systems. The study
      of stress-induced analgesia has enhanced our understanding of the fundamental
      physiology of pain and stress and can be a useful approach for uncovering new
      therapeutic targets for the treatment of pain and stress-related disorders.

PMID- 19393289
TI  - Brain to music to brain!
AB  - It has been implicitly understood that culture and music as collective products
      of human brain in turn influence the brain itself. Now, imaging and anatomical
      data add substance to this notion. The impact of playing piano on the brain of
      musicians and its possible effects on cultural and neurological evolution are
      briefly discussed.

PMID- 19393290
TI  - The definition of EPCs and other bone marrow cells contributing to
      neoangiogenesis and tumor growth: is there common ground for understanding the
      roles of numerous marrow-derived cells in the neoangiogenic process?
AB  - Interest in the regulation of blood vessel formation as a mechanism to permit
      unregulated tumor cell growth was a prescient hypothesis of Dr. Judah Folkman
      nearly 3 decades ago. Understanding the cellular and molecular mechanisms that
      affect the recruitment, expansion, and turnover of the tumor microvasculature
      continues to evolve. While the fundamental paradigms for improving blood flow to
      growing, injured, diseased, or tumor infiltrated tissues are well known, the
      potential role of bone marrow derived circulating endothelial progenitor cells
      (EPCs) to function as postnatal vasculogenic precursors for tumor
      microvasculature has become a controversial premise. We will briefly review some
      recently published high profile papers that appear to derive polar
      interpretations for the role of EPCs in the angiogenic switch and discuss
      possible reasons for the disparate views in work conducted in both mouse and man.

PMID- 19393291
TI  - Inferior olive oscillation as the temporal basis for motricity and oscillatory
      reset as the basis for motor error correction.
AB  - The cerebellum can be viewed as supporting two distinct aspects of motor
      execution related to a) motor coordination and the sequence that imparts such
      movement temporal coherence and b) the reorganization of ongoing movement when a
      motor execution error occurs. The former has been referred to as "motor time
      binding" as it requires that the large numbers of motoneurons involved be
      precisely activated from a temporal perspective. By contrast, motor error
      correction requires the abrupt reorganization of ongoing motor sequences, on
      occasion sufficiently important to rescue the animal or person from potentially
      lethal situations. The olivo-cerebellar system plays an important role in both
      categories of motor control. In particular, the morphology and electrophysiology
      of inferior olivary neurons have been selected by evolution to execute a rather
      unique oscillatory pace-making function, one required for temporal sequencing and
      a unique oscillatory phase resetting dynamic for error correction. Thus, inferior
      olivary (IO) neurons are electrically coupled through gap junctions, generating
      synchronous subthreshold oscillations of their membrane potential at a frequency
      of 1-10 Hz and are capable of fast and reliable phase resetting. Here I propose
      to address the role of the olivocerebellar system in the context of motor timing
      and reset.

PMID- 19393292
TI  - Two distinct populations of projection neurons in the rat lateral parafascicular
      thalamic nucleus and their cholinergic responsiveness.
AB  - The lateral parafascicular nucleus (lPf) is a member of the intralaminar thalamic
      nuclei, a collection of nuclei that characteristically provides widespread
      projections to the neocortex and basal ganglia and is associated with arousal,
      sensory, and motor functions. Recently, lPf neurons have been shown to possess
      different characteristics than other cortical-projecting thalamic relay neurons.
      We performed whole cell recordings from lPf neurons using an in vitro rat slice
      preparation and found two distinct neuronal subtypes that were differentiated by
      distinct morphological and physiological characteristics: diffuse and bushy.
      Diffuse neurons, which had been previously described, were the predominant
      neuronal subtype (66%). These neurons had few, poorly-branching, extended
      dendrites, and rarely displayed burst-like action potential discharge, a
      ubiquitous feature of thalamocortical relay neurons. Interestingly, we discovered
      a smaller population of bushy neurons (34%) that shared similar morphological and
      physiological characteristics with thalamocortical relay neurons of primary
      sensory thalamic nuclei. In contrast to other thalamocortical relay neurons,
      activation of muscarinic cholinergic receptors produced a membrane
      hyperpolarization via activation of M(2) receptors in most lPf neurons (60%). In
      a minority of lPf neurons (33%), muscarinic agonists produced a membrane
      depolarization via activation of predominantly M(3) receptors. The muscarinic
      receptor-mediated actions were independent of lPf neuronal subtype (i.e. diffuse
      or bushy neurons); however the cholinergic actions were correlated with lPf
      neurons with different efferent targets. Retrogradely-labeled lPf neurons from
      frontal cortical fluorescent bead injections primarily consisted of bushy type
      lPf neurons (78%), but more importantly, all of these neurons were depolarized by
      muscarinic agonists. On the other hand, lPf neurons labeled by striatal
      injections were predominantly hyperpolarized by muscarinic agonists (63%). Our
      results indicate two distinct subpopulations of lPf projection neurons, and
      interestingly lPf neurons respond differentially to muscarinic receptor
      activation based on their axonal target.

PMID- 19393293
TI  - alpha-Tocopherol decreases the somatostatin receptor-effector system and
      increases the cyclic AMP/cyclic AMP response element binding protein pathway in
      the rat dentate gyrus.
AB  - Neuronal survival has been shown to be enhanced by alpha-tocopherol and modulated
      by cyclic AMP (cAMP). Somatostatin (SST) receptors couple negatively to adenylyl
      cyclase (AC), thus leading to decreased cAMP levels. Whether alpha-tocopherol can
      stimulate neuronal survival via regulation of the somatostatinergic system,
      however, is unknown. The aim of this study was to investigate the effects of
      alpha-tocopherol on the SST signaling pathway in the rat dentate gyrus. To that
      end, 15-week-old male Sprague-Dawley rats were treated daily for 1 week with (+)
      alpha-tocopherol or vehicle and sacrificed on the day following the last
      administration. No changes in either SST-like immunoreactivity (SST-LI) content
      or SST mRNA levels were detected in the dentate gyrus as a result of alpha
      tocopherol treatment. A significant decrease in the density of the SST binding
      sites and an increase in the dissociation constant, however, were detected. The
      lower SST receptor density in the alpha-tocopherol-treated rats correlated with a
      significant decrease in the protein levels of the SST receptor subtypes SSTR1
      SSTR4, whereas the corresponding mRNA levels were unaltered. G-protein-coupled
      receptor kinase 2 expression was decreased by alpha-tocopherol treatment. This
      vitamin induced a significant increase in both basal and forskolin-stimulated AC
      activity, as well as a decrease in the inhibitory effect of SST on AC. Whereas
      the protein levels of AC type V/VI were not modified by alpha-tocopherol
      administration, ACVIII expression was significantly enhanced, suggesting it might
      account for the increase in AC activity. In addition, this treatment led to a
      reduction in Gialpha1-3 protein levels and in Gi functionality. alpha-Tocopherol
      did not affect the expression of the regulator of G-protein signaling 6/7
      (RGS6/7). Finally, alpha-tocopherol induced an increase in the levels of
      phosphorylated cAMP response element binding protein (p-CREB) and total CREB in
      the dentate gyrus. Since CREB synthesis and phosphorylation promote the survival
      of many cells, including neurons, whereas SST inhibits the cAMP-PKA pathway,
      which is known to be involved in CREB phosphorylation, the alpha-tocopherol
      induced reduction of SSTR observed here might possibly contribute, via increased
      cAMP levels and CREB activity, to the mechanism by which this vitamin promotes
      the survival of newborn neurons in the dentate gyrus.

PMID- 19393294
TI  - The genetics of schizophrenia.
AB  - Research on the genetic factors conferring risk for schizophrenia has not
      provided definitive answers. In the present review, we will discuss potential
      clinical and genetic limitations intrinsic to the strategies using a diagnostic
      phenotype. Among clinical factors, uncertainty of the phenotype is certainly a
      major limitation. Genetic problems include locus heterogeneity and the complex
      genetic architecture of the phenotype. Given these limiting factors, we will also
      discuss another hypothesis-driven strategy to uncover genetic risk: the use of
      quantitative measures (intermediate phenotypes) within more specific
      neurobiological mechanisms. As a clear example of all these issues and because of
      the longstanding involvement in the pathophysiology of this disorder, we will
      review the association of the gene for dopamine D2 receptors (DRD2) with
      diagnosis of schizophrenia and with specific working memory behavioral and brain
      activity phenotypes. We conclude by suggesting that hypothesis-free and
      hypothesis-driven are not mutually exclusive strategies and may provide
      information at different levels that are both useful and equally valid about
      genetic risk for a complex diagnostic entity like schizophrenia and for a complex
      phenotype like psychosis.

PMID- 19393295
TI  - Coping with defeat: acute glucocorticoid and forebrain responses to social defeat
      vary with defeat episode behaviour.
AB  - Individuals vary in the way in which they cope with stressful situations. It has
      been suggested that 'active' coping behaviour, characterised by aggression and
      territorial control, is more effective in moderating the stress associated with
      social defeat than 'passive' coping behaviour, as characterised by immobility,
      decreased reactivity, and low aggression. We used the rodent 'resident/intruder'
      paradigm to determine whether individual differences in coping behaviour modulate
      the acute adrenocortical response to social defeat. During the 10 min conflict
      episode, behaviours displayed by the intruder were recorded and subsequently
      scored. Intruders that engaged in large numbers of fights and/or frequently used
      physical structures to block the resident's approach (a behaviour referred to as
      'guarding'), displayed smaller corticosterone responses to defeat than other
      intruders. Corticosterone responses to defeat were unrelated to a measure of
      coping style preferences (defensive burying test) obtained prior to the defeat
      encounter. We further chose to investigate the neurobiological basis of this
      observation by comparing the patterns of defeat-induced neuronal activation in
      the forebrains of intruders that displayed high versus low numbers of defensive
      behaviours during the defeat episode. The results of this analysis indicated that
      'low fight' and 'low guard' intruders, i.e. those that achieved a fight or a
      guard score below the 20th percentile, had significantly higher numbers of Fos
      positive neurons in forebrain regions such as the medial prefrontal cortex and
      the amygdala than did control animals exposed to an empty resident's cage. In
      summary, the present data suggest that 'active' coping behaviour is associated
      with both a smaller adrenocortical response and a lower level of 'neural
      activation' following social defeat. This outcome differs from that of earlier
      studies, a difference that we suggest is due to the fact that the present study
      is the first to assess coping on the basis of behaviour actually displayed during
      the conflict interaction.

PMID- 19393296
TI  - Dominant rats are natural risk takers and display increased motivation for food
      reward.
AB  - Risk-taking behavior is a vital aspect mediating the formation of social
      structure in animals. Here, we utilized the visible burrow system (VBS), a model
      in which rats form dominance hierarchies, to test the hypothesis that dominant
      rats in the VBS are natural risk takers and display an increased motivational
      state after VBS exposure. In particular, we predicted that dominant rats would
      have attenuated anxiety-like behavior and augmented acquisition of operant
      responding for food reward relative to subordinate and controls. We further
      hypothesized that these behaviors would correlate with elevated mesocortical
      orexin signaling. Prior to burrow exposure, male Long-Evans rats were tested on
      the elevated plus maze (EPM), and subsequently exposed to the VBS for seven
      consecutive days. At the conclusion of burrow exposure body weight and plasma
      corticosterone were used to confirm social rank within each colony.
      Interestingly, rats that went on to become dominant in the VBS spent
      significantly more time in the open arms of the EPM prior to burrow exposure and
      displayed increased operant responding for food reward. This effect was present
      over a range of reinforcement schedules and also persisted for up to 1 month
      following VBS exposure. Moreover, dominant rats displayed increased orexin
      receptor mRNA in the medial prefrontal cortex (mPFC) relative to subordinate and
      control rats. These data support previous findings from our group and are
      consistent with the hypothesis that risk-taking behavior may precede dominance
      formation in social hierarchies.

PMID- 19393297
TI  - Compartmentalized expression of light-induced clock genes in the suprachiasmatic
      nucleus of the diurnal grass rat (Arvicanthis niloticus).
AB  - Photic responses of the circadian system are mediated through light-induced clock
      gene expression in the suprachiasmatic nucleus (SCN). In nocturnal rodents,
      depending on the timing of light exposure, Per1 and Per2 gene expression shows
      distinct compartmentalized patterns that correspond to the behavioral responses.
      Whether the gene- and region-specific induction patterns are unique to nocturnal
      animals, or are also present in diurnal species is unknown. We explored this
      question by examining the light-induced Per1 and Per2 gene expression in
      functionally distinct SCN subregions, using diurnal grass rats Arvicanthis
      niloticus. Light exposure during nighttime induced Per1 and Per2 expression in
      the SCN, showing unique spatiotemporal profiles depending on the phase of the
      light exposure. After a phase delaying light pulse (LP) in the early night,
      strong Per1 induction was observed in the retinorecipient core region of the SCN,
      while strong Per2 induction was observed throughout the entire SCN. After a phase
      advancing LP in the late night, Per1 was first induced in the core and then
      extended into the whole SCN, accompanied by a weak Per2 induction. This
      compartmentalized expression pattern is very similar to that observed in
      nocturnal rodents, suggesting that the same molecular and intercellular pathways
      underlying acute photic responses are present in both diurnal and nocturnal
      species. However, after an LP in early subjective day, which induces phase
      advances in diurnal grass rats, but not in nocturnal rodents, we did not observe
      any Per1 or Per2 induction in the SCN. This result suggests that in spite of
      remarkable similarities in the SCN of diurnal and nocturnal rodents, unique
      mechanisms are involved in mediating the phase shifts of diurnal animals during
      the subjective day.

PMID- 19393298
TI  - Aquaporin-4 maintains ependymal integrity in adult mice.
AB  - Ependymal cells form the walls of the ventricles, and take part in the production
      of cerebrospinal fluid (CSF). Aquaporin-4 (AQP4), a predominant water channel of
      the brain, is restricted to basolateral plasma membranes of ependymal cells. The
      highly polarized expression of AQP4 suggests it may be involved in maintaining
      the structural and functional integrity of the ependyma. This hypothesis was
      validated by using adult AQP4 knockout mice generated by our laboratory [Fan Y,
      Zhang J, Sun XL, Gao L, Zeng XN, Ding JH, Cao C, Niu L, Hu G (2005) Sex- and
      region-specific alterations of basal amino acid and monoamine metabolism in the
      brain of aquaporin-4 knockout mice. J Neurosci Res 82:458-464]. Histological
      analysis showed disorganized ependymal layer of the lateral ventricle and
      aqueduct in AQP4-deficiency mice. A majority (92.7%) of null mice displayed
      reduced lateral ventricular volume, while a small fraction (7.3%) had enlarged or
      normal ventricular size with a narrow aqueduct. Immunohistochemistry demonstrated
      that AQP4 deletion resulted in decreased expression of gap junction protein
      connexin43 in the ependymal cells. Electron microscopy confirmed junctional
      complex absence at basolateral membranes of ependymocytes. Moreover, AQP4
      knockout mice showed decreased CSF production and increased brain water content
      compared with wild-type mice. These results highlight a key role of AQP4 in
      maintaining the structure and function of the ependyma. In addition, variable
      profiles of ventricle system in adult AQP4 null mice indicate functional AQP4
      polymorphisms.

PMID- 19393300
TI  - Detection of behavioral alterations and learning deficits in mice lacking
      synaptophysin.
AB  - The integral membrane protein synaptophysin is one of the most abundant
      polypeptide components of synaptic vesicles. It is not essential for
      neurotransmission despite its abundance but is believed to modulate the
      efficiency of the synaptic vesicle cycle. Detailed behavioral analyses were
      therefore performed on synaptophysin knockout mice to test whether synaptophysin
      affects higher brain functions. We find that these animals are more exploratory
      than their wild type counterparts examining novel objects more closely and
      intensely in an enriched open field arena. We also detect impairments in learning
      and memory, most notably reduced object novelty recognition and reduced spatial
      learning. These deficits are unlikely caused by impaired vision, since all
      electroretinographic parameters measured were indistinguishable from those in
      wild type controls although an inverse optomotor reaction was observed. Taken
      together, our observations demonstrate functional consequences of synaptophysin
      depletion in a living organism.

PMID- 19393299
TI  - Developmental regulation of neural cell adhesion molecule in human prefrontal
      cortex.
AB  - Neural cell adhesion molecule (NCAM) is a membrane-bound cell recognition
      molecule that exerts important functions in normal neurodevelopment including
      cell migration, neurite outgrowth, axon fasciculation, and synaptic plasticity.
      Alternative splicing of NCAM mRNA generates three main protein isoforms: NCAM
      180, -140, and -120. Ectodomain shedding of NCAM isoforms can produce an
      extracellular 105-115 kilodalton soluble neural cell adhesion molecule fragment
      (NCAM-EC) and a smaller intracellular cytoplasmic fragment (NCAM-IC). NCAM also
      undergoes a unique post-translational modification in brain by the addition of
      polysialic acid (PSA)-NCAM. Interestingly, both PSA-NCAM and NCAM-EC have been
      implicated in the pathophysiology of schizophrenia. The developmental expression
      patterns of the main NCAM isoforms and PSA-NCAM have been described in rodent
      brain, but no studies have examined NCAM expression across human cortical
      development. Western blotting was used to quantify NCAM in human postmortem
      prefrontal cortex in 42 individuals ranging in age from mid-gestation to early
      adulthood. Each NCAM isoform (NCAM-180, -140, and -120), post-translational
      modification (PSA-NCAM) and cleavage fragment (NCAM-EC and NCAM-IC) demonstrated
      developmental regulation in frontal cortex. NCAM-180, -140, and -120, as well as
      PSA-NCAM, and NCAM-IC all showed strong developmental regulation during fetal and
      early postnatal ages, consistent with their identified roles in axon growth and
      plasticity. NCAM-EC demonstrated a more gradual increase from the early postnatal
      period to reach a plateau by early adolescence, potentially implicating
      involvement in later developmental processes. In summary, this study implicates
      the major NCAM isoforms, PSA-NCAM and proteolytically cleaved NCAM in pre- and
      postnatal development of the human prefrontal cortex. These data provide new
      insights on human cortical development and also provide a basis for how altered
      NCAM signaling during specific developmental intervals could affect synaptic
      connectivity and circuit formation, and thereby contribute to neurodevelopmental
      disorders.

PMID- 19393301
TI  - Dietary curcumin supplementation counteracts reduction in levels of molecules
      involved in energy homeostasis after brain trauma.
AB  - Traumatic brain injury (TBI) is followed by an energy crisis that compromises the
      capacity of the brain to cope with challenges, and often reduces cognitive
      ability. New research indicates that events that regulate energy homeostasis
      crucially impact synaptic function and this can compromise the capacity of the
      brain to respond to challenges during the acute and chronic phases of TBI. The
      goal of the present study is to determine the influence of the phenolic yellow
      curry pigment curcumin on molecular systems involved with the monitoring,
      balance, and transduction of cellular energy, in the hippocampus of animals
      exposed to mild fluid percussion injury (FPI). Young adult rats were exposed to a
      regular diet (RD) without or with 500 ppm curcumin (Cur) for four weeks, before
      an FPI was performed. The rats were assigned to four groups: RD/Sham, Cur/Sham,
      RD/FPI, and Cur/FPI. We found that FPI decreased the levels of AMP-activated
      protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and
      cytochrome c oxidase II (COX-II) in RD/FPI rats as compared to the RD/sham rats.
      The curcumin diet counteracted the effects of FPI and elevated the levels of
      AMPK, uMtCK, COX-II in Cur/FPI rats as compared to RD/sham rats. In addition, in
      the Cur/sham rats, AMPK and uMtCK increased compared to the RD/sham. Results show
      the potential of curcumin to regulate molecules involved in energy homeostasis
      following TBI. These studies may foster a new line of therapeutic treatments for
      TBI patients by endogenous upregulation of molecules important for functional
      recovery.

PMID- 19393302
TI  - Fruitlet abscission: A cDNA-AFLP approach to study genes differentially expressed
      during shedding of immature fruits reveals the involvement of a putative auxin
      hydrogen symporter in apple (Malus domestica L. Borkh).
AB  - Apple Malus X domestica fruitlet abscission is preceded by a stimulation of
      ethylene biosynthesis and a gain in sensitivity to the hormone. This phase was
      studied by a differential screening carried out by cDNA-AFLP in abscising (AF)
      and non-abscising (NAF) fruitlet populations. Fifty-three primer combinations
      allowed for the isolation of 131, 66 and 30 differentially expressed bands from
      cortex, peduncle and seed, respectively. All sequences were then classified as up
      or down-regulated by comparing the profile in AFs and NAFs. Almost all of these
      sequences showed significant homology to genes encoding proteins with known or
      putative function. The gene ontology analysis of the TDFs isolated indicated a
      deep change in metabolism, plastid and hormonal status, especially auxin.
      Furthermore, some common elements between abscission and senescence were
      identified. The isolation of the full length of one of these TDFs allowed for the
      identification of a gene encoding an auxin hydrogen symporter (MdAHS).
      Bioinformatic analysis indicated that the deduced protein shares some features
      with other auxin efflux carriers, which include PINs. Nevertheless the 3D
      structure pointed out substantial differences and a conformation largely
      dissimilar from canonical ion transporters. The expression analysis demonstrated
      that this gene is regulated by light and development but not affected by ethylene
      or auxin.

PMID- 19393303
TI  - Effects of constitutive expression of somatolactin alpha on skin pigmentation in
      medaka.
AB  - Somatolactin alpha (SLa) is a fish-specific peptide hormone secreted from the
      pituitary. Its functions have been investigated for the last decade but are still
      under debate. We previously reported a frame-shift mutation on SLa in a medaka
      mutant, color interfere (ci), which shows defects in body-color regulation, lipid
      storage, and cortisol secretion. In this study, we examined the effects of
      introducing a DNA fragment which constitutively expresses wild-type SLa under
      regulation of the beta-actin (Actb) promoter into the ci genome. We successfully
      visualized the transgene expression by taking advantage of an internal ribosome
      entry site (IRES) and the green fluorescent protein (GFP). The transgenic medaka,
      Actb-SLa:GFP, exhibited a reversed body-color phenotype of ci; more orange
      xanthophores and less white leucophores. We also detected more black melanophores
      and less silver iridophores, which indicates SLa's comprehensive role in
      regulating all types of pigment cells in the skin. Unexpectedly, the defects in
      lipid/cortisol contents remained in Actb-SLa:GFP. Therefore, the causal
      relationship between SLa and lipid/cortisol metabolisms relapses to an open
      question which needs to be reassessed by other types of experiments. Both the
      Actb-SLa:GFP and ci fish grow and mature similar to wild type, indicating SLa
      contributes little to growth regulation in spite of the fact that it binds to a
      teleost-specific paralog of growth-hormone receptor in vitro. The present study
      provides definitive evidence for SLa's principal and indispensable role in body
      color regulation in medaka.

PMID- 19393304
TI  - The RJL family of small GTPases is an ancient eukaryotic invention probably
      functionally associated with the flagellar apparatus.
AB  - A patchily distributed gene family is often taken as evidence for horizontal gene
      transfer (HGT) events, but it may also result solely from multiple gene losses.
      The RJL family of uncharacterised Ras-like GTPases was previously suggested to
      have undergone HGT events between protists and deuterostome metazoans, owing to
      the apparent absence of RJL in intermediate groups (Nepomuceno-Silva, J.L., de
      Melo, L.D., Mendonca, S.M., Paixao, J.C., Lopes, U.G., 2004. RJLs: a new family
      of Ras-related GTP-binding proteins. Gene 327, 221-232). We have reanalysed the
      phylogenetic distribution and phylogeny of the RJL family, taking advantage of
      the recent expansion of sequence data available from diverse eukaryotes. We found
      that RJL orthologs are much more widely distributed than previously assumed. At
      least one representative encoding an RJL protein could be identified for each of
      the six major eukaryotic "supergroups" (Opisthokonta, Amoebozoa, Excavata,
      Archaeplastida, Chromalveolata, and Rhizaria) as well as for a species of
      Apusomonadida, a deep lineage that may not be specifically related to any of the
      recognized supergroups. Phylogenetic analyses do not support HGT of RJL genes
      between the major eukaryotic lineages, indicating that the RJL family was present
      in the last eukaryotic common ancestor and was lost several times over the course
      of eukaryotic evolution. Interestingly, RJL was lost from all taxa lacking
      flagellated cells and from a few lineages that build structurally unusual or
      reduced flagella, raising the intriguing possibility that RJL proteins are
      functionally associated with the flagellar apparatus. The RJL GTPase domain has
      been fused with the DnaJ domain on two separate occasions: in the Holozoa (before
      the split of Metazoa and choanoflagellates), giving rise to the previously known
      Rbj type of RJL with the DnaJ domain at the C-terminus, and independently in
      Alveolata resulting in novel proteins with the DnaJ domain at the N-terminus.
      These independent fusions suggest that RJL proteins may generally function via
      regulating the DnaJ-Hsp70 module.

PMID- 19393305
TI  - Design, preparation, in vitro and in vivo evaluation of (99m)Tc-N2S2-Tat(49-57)
      bombesin: a target-specific hybrid radiopharmaceutical.
AB  - The gastrin-releasing peptide receptor (GRP-r) is over-expressed in various human
      tumors. Recently, (99m)Tc-EDDA/HYNIC-Lys(3)-bombesin ((99m)Tc-BN) was reported as
      a radiopharmaceutical with specific cell GRP-r binding and images in breast
      cancer patients demonstrated distinct radioactivity accumulation in malignant
      tissue. The HIV Tat-derived peptide has been used to deliver a large variety of
      cargoes into cells. Therefore, a new hybrid radiopharmaceutical of type (99m)Tc
      N(2)S(2)-Tat(49-57)-Lys(3)-bombesin ((99m)Tc-Tat-BN) would increase cell uptake.
      The aim of this research was to prepare and assess in vitro and in vivo uptake
      kinetics in cancer cells of (99m)Tc-Tat-BN and to compare its cellular
      internalization with that of (99m)Tc-BN. Structures of N(2)S(2)-Tat-BN and
      Tc(O)N(2)S(2)-Tat-BN were calculated by an MM procedure. (99m)Tc-Tat-BN was
      synthesized and stability studies carried out by HPLC and ITLC-SG analyses in
      serum and cysteine solutions. In vitro internalization was tested using human
      prostate cancer PC-3 cells and breast carcinoma cell lines MDA-MB231 and MCF7.
      Biodistribution was determined in PC-3 tumor-bearing nude mice. Results showed a
      minimum energy of 271 kcal/mol for N(2)S(2)-Tat-BN and 300 kcal/mol for
      Tc(O)N(2)S(2)-Tat-BN. (99m)Tc-Tat-BN radiochemical purity was >90%. In vitro
      studies demonstrated stability in serum and cysteine solutions, specific cell
      receptor binding and internalization in three cell lines was significantly higher
      than that of (99m)Tc-BN (p<0.05). The tumor-to-muscle radioactivity ratio was 8.5
      for (99m)Tc-Tat-BN and 7 for (99m)Tc-BN. Therefore, this hybrid is potentially
      useful in breast and prostate cancer imaging.

PMID- 19393306
TI  - Interactions of auditory and visual stimuli in space and time.
AB  - The nervous system has evolved to transduce different types of environmental
      energy independently, for example light energy is transduced by the retina
      whereas sound energy is transduced by the cochlea. However, the neural processing
      of this energy is necessarily combined, resulting in a unified percept of a real
      world object or event. These percepts can be modified in the laboratory,
      resulting in illusions that can be used to probe how multisensory integration
      occurs. This paper reviews studies that have utilized such illusory percepts in
      order to better understand the integration of auditory and visual signals in
      primates. Results from human psychophysical experiments where visual stimuli
      alter the perception of acoustic space (the ventriloquism effect) are discussed,
      as are experiments probing the underlying cortical mechanisms of this
      integration. Similar psychophysical experiments where auditory stimuli alter the
      perception of visual temporal processing are also described.

PMID- 19393307
TI  - Relation of focal hair-cell lesions to noise-exposure parameters from a 4- or a
      0.5-kHz octave band of noise.
AB  - In a previous study, we examined the relation between total energy in a noise
      exposure and the percentage losses of outer (OHC) and inner (IHC) hair cells in
      the basal and apical halves of 607 chinchilla cochleae [Harding, G.W., Bohne,
      B.A., 2004a. Noise-induced hair-cell loss and total exposure energy: analysis of
      a large data set. J. Acoust. Soc. Am. 115, 2207-2220]. The animals had been
      exposed continuously to either a 4-kHz octave band of noise (OBN) at 47-108 dB
      SPL for 0.5h-36 d, or a 0.5-kHz OBN at 65-128 dB SPL for 3.5h-433 d. Interrupted
      exposures were also employed with both OBNs. Post-exposure recovery times ranged
      from 0 to 913 days. Cluster analysis was used to separate the data into three
      magnitudes of damage. The data were also separated into recovery times of 0 days
      (acute) and >0 days (chronic) and the apical and basal halves of the organ of
      Corti (OC). A substantial part of these hair-cell losses occurred in focal
      lesions (i.e., >or=50% loss of IHCs, OHCs or both over a distance of >or=0.03
      mm). This aspect of the damage from noise was not included in the previous
      analysis. The present analysis describes, within the same three clusters, the
      apex-to-base distribution of 1820 focal lesions found in 468 of 660 (71%) noise
      exposed cochleae. In these cochleae, OC length in mm was converted to percent
      distance from the apex. The lesion data were analyzed for location in percent
      distance from the apex and size (mm) of the lesions. In 55 of 140 (39%) non-noise
      exposed, control OCs, there were 186 focal hair-cell lesions, the characteristics
      of which were also determined. Focal lesions with hair-cell loss >or=50% involved
      predominantly OHCs, IHCs only, or both OHCs and IHCs (i.e., combined OHC-IHC
      lesions). The predominantly OHC and combined lesions were pooled together for the
      analysis. The distributions of lesion location (in percent distance from the
      apex), weighted by lesion size (in percent of OC length) were tallied in 2%
      distance bins. In controls, focal lesions were uniformly distributed from apex to
      base and 70% of them were pure IHC lesions. In cochleae exposed to the 4-kHz OBN,
      lesions were distributed throughout the basal half of the OC. In cochleae exposed
      to the 0.5-kHz OBN, lesions occurred in both halves of the OC. With continuous
      exposures, 74% of the lesions were predominantly OHC or combined lesions. With
      interrupted exposures, 52% of the lesions were OHC or combined lesions. Lesion
      size was generally larger in the chronic compared to acute cochleae with similar
      exposures. There was a minimum total energy at which focal lesions began to
      appear and slightly higher energies resulted in nearly all exposed cochleae
      having focal lesions.

PMID- 19393308
TI  - Biotechnological and industrial significance of cyanobacterial secondary
      metabolites.
AB  - Cyanobacteria are considered to be a rich source of novel metabolites of a great
      importance from a biotechnological and industrial point of view. Some
      cyanobacterial secondary metabolites (CSMs), exhibit toxic effects on living
      organisms. A diverse range of these cyanotoxins may have ecological roles as
      allelochemicals, and could be employed for the commercial development of
      compounds with applications such as algaecides, herbicides and insecticides.
      Recently, cyanobacteria have become an attractive source of innovative classes of
      pharmacologically active compounds showing interesting and exciting biological
      activities ranging from antibiotics, immunosuppressant, and anticancer,
      antiviral, antiinflammatory to proteinase-inhibiting agents. A different but not
      less interesting property of these microorganisms is their capacity of overcoming
      the toxicity of ultraviolet radiation (UVR) by means of UV-absorbing/screening
      compounds, such as mycosporine-like amino acids (MAAs) and scytonemin. These last
      two compounds are true 'multipurpose' secondary metabolites and considered to be
      natural photoprotectants. In this sense, they may be biotechnologically exploited
      by the cosmetic industry. Overall CSMs are striking targets in biotechnology and
      biomedical research, because of their potential applications in agriculture,
      industry, and especially in pharmaceuticals.

PMID- 19393309
TI  - Cadmium tolerance and accumulation in eight potential energy crops.
AB  - The production of energy crops that can be used for biodiesel production is a
      sustainable approach for the removal of metal pollutants by phytoremediation.
      This study investigated the cadmium (Cd) accumulation and tolerance of eight
      potential energy crops. After growth for 28 days in substrates containing 0, 50,
      100 or 200 mg Cd x kg(-1), seedlings were evaluated for growth parameters,
      chlorophyll content, chlorophyll fluorescence parameters and Cd accumulation. All
      eight crops were moderately tolerant to Cd toxicity, with four [i.e., hemp
      (Cannabis sativa), flax (Linum usitatissimum), castor (Ricinus communis) and
      peanut (Arachis hypogaea)] being more tolerant than the others. Three of these
      crops (hemp, flax and peanut) had higher Cd accumulation capacities. The roots of
      peanut and hemp had high bioconcentration factors (BCF>1000), while flax shoots
      accumulated a higher concentration of Cd (>100 mg/kg). These results demonstrate
      that it is possible to grow energy crops on Cd-contaminated soil. Hemp, flax and
      peanut are excellent candidates for phytoremediation.

PMID- 19393310
TI  - Yeast strains for ethanol production from lignocellulosic hydrolysates during in
      situ detoxification.
AB  - Yeast strains Y1, Y4 and Y7 demonstrated high conversion efficiencies for sugars
      and high abilities to tolerate or metabolize inhibitors in dilute-acid
      lignocellulosic hydrolysates. Strains Y1 and Y4 completely consumed the glucose
      within 24 h in dilute-acid lignocellulosic hydrolysate during in situ
      detoxification, and the maximum ethanol yields reached 0.49 g and 0.45 g
      ethanol/g glucose, equivalent to maximum theoretical values of 96% and 88.2%,
      respectively. Strain Y1 could metabolize xylose to xylitol with a yield of 0.64
      g/g xylose, whereas Y4 was unable to utilize xylose as a substrate. Strain Y7 was
      able to consume sugars (glucose and xylose) within 72 h during hydrolysate in
      situ detoxification, producing a high ethanol yield (equivalent to 93.6% of the
      maximum theoretical value). Y1 and Y7 are the most efficient yeast strains yet
      reported for producing ethanol from non-detoxified dilute-acid lignocellulosic
      hydrolysates. These findings offer huge potential for improving the economics of
      bio-ethanol production from lignocellulosic hydrolysates.

PMID- 19393311
TI  - Scale study of direct synthesis of dimethyl ether from biomass synthesis gas.
AB  - We investigated the synthesis of dimethyl ether (DME) from biomass synthesis gas
      using a kind of hybrid catalyst consisting of methanol and HZSM-5 zeolite in a
      fixed-bed reactor in a 100 ton/year pilot plant. The biomass synthesis gas was
      produced by oxygen-rich gasification of corn core in a two-stage fixed bed. The
      results showed that CO conversions reached 82.00% and 73.55%, the selectivities
      for DME were 73.95% and 69.73%, and the space-time yields were 124.28 kg m(-3) h(
      1) and 203.80 kg m(-3) h(-1) when gas hourly space velocities were 650 h(-1) and
      1200 h(-1), respectively. Deoxidation and tar removal from biomass synthesis gas
      was critical to the stable operation of the DME synthesis system. Using single
      pass synthesis, the H(2)/CO ratio improved from 0.98-1.17 to 2.12-2.22. The yield
      of DME would be increased greatly if the exhaust was reused after removal of the
      CO(2).

PMID- 19393313
TI  - Retrospective analysis of relative parameter sensitivity in multi-generation
      reproductive toxicity studies.
AB  - Current suggestions towards amending the OECD two-generation protocol include
      omission of the second generation and inclusion of additional parameters. This
      study analysed the relative parameter sensitivity in 18 individually published
      multi-generation studies with substances toxic to fertility. Among parameters
      that most often determined the reproductive LOAEL were weight of testis, dam and
      pup as well as litter size. Several other parameters were found to be unaffected
      in all studies evaluated. Some substances affected a specific set of parameters,
      indicating that rarely affected parameters may prove crucial in individual
      situations. This argues for the inclusion of a wide spectrum of parameters to
      cover all possible effects. Less sensitive parameters, mechanistically related to
      more sensitive ones, may be omitted as they will unlikely contribute to the
      overall LOAEL. This study gives first insights and needs follow-up by more
      extensive analyses before firm conclusions on the design of the two-generation
      study protocol can be drawn.

PMID- 19393312
TI  - Hydrogen-producing capability of anaerobic activated sludge in three types of
      fermentations in a continuous stirred-tank reactor.
AB  - A continuous stirred-tank reactor was used as an anaerobic sludge system and the
      hydrogen production capabilities of three typical fermentations, in terms of
      specific hydrogen production rates, were investigated under the same hydraulic
      retention times (8 h) and influent chemical oxygen demand (5000 mg/L) at 35
      degrees C. The reactor was continuously fed with diluted molasses, while the pH
      and oxidation reduction potential in the reactor were regulated to control the
      type of fermentation. The specific hydrogen production rate of the anaerobic
      sludge reached 2.96 mol/kg mixed liquid volatile suspended solid (MLVSS)/day,
      (mol x kg MLVSS(-1) d(-1)), in ethanol-type fermentation, while 0.57 mol x kg
      MLVSS(-1) d(-1) in butyric acid-type fermentation, and 0.022 mol x kg MLVSS(-1)
      d(-1) in propionic acid-type fermentation. The hydrogen production capability of
      ethanol-type fermentation was 4.11 times greater than that of butyric acid-type
      fermentation and 148 times that of propionic acid-type fermentation.

PMID- 19393314
TI  - Use of 65kDa mannoprotein gene primers in PCR methods for the identification of
      five medically important Candida species.
AB  - We have developed PCR and Multiplex PCR assays for the detection of medically
      important Candida spp. using different species and genus-specific PCR primers
      selected within the MP65 gene, a recently cloned gene encoding a mannoprotein
      adhesin. The genus-specific PCR primers were able to amplify Candida species DNA
      (100% positivity) whereas DNA from all other isolates tested, belonging to other
      fungal genera, was not amplified. The species-specific PCR primers allowed
      differentiation of each of five Candida species by the amplicon length produced.
      No amplicons were detected using species- or genus-specific primers in several
      bacterial or human DNA templates. The methods described in this study are
      reproducible, simple and specific. The total time required for each PCR method
      was less than 4 h from the extraction to the visualized amplicons after PCR. In
      conclusion, we developed PCR methods to differentiate the five most medically
      important Candida species using primers directed to the MP65 gene.

PMID- 19393315
TI  - Multiple mechanisms of soy isoflavones against oxidative stress-induced
      endothelium injury.
AB  - Diabetic vascular complications are related to a combination of oxidative stress
      and hyperglycemia. Here we investigate the effect and mechanism of soy
      isoflavones on oxidative stress-induced endothelial cell injury. Oxidative stress
      was modeled in primary cultured human umbilical vein endothelial cells by
      incubation with H(2)O(2) and high glucose. Genistein and daidzein protected the
      cells against H(2)O(2)-induced apoptosis and their protective actions were
      abolished by ICI 182780, an estrogen receptor antagonist. The inhibition of cell
      proliferation by oxidative stress was prevented by genistein and daidzein under
      normal glucose conditions, but they were less effective at high glucose levels.
      Genistein and daidzein upregulated the estrogen receptor ERbeta and increased Bcl
      2 expression. Silencing of Bcl-2 with siRNA abolished the protection of
      genistein. Moreover, inhibition of the PI3K and Rho A/Rho kinase pathways by
      wortmannin and Y-27632 altered the effects of genistein and daidzein on cell
      survival. We conclude that oxidative stress-induced apoptosis and cell
      proliferation inhibition can be prevented by soy isoflavones via the regulation
      of ERbeta and Bcl-2/Bax expression and modulation of cell survival signaling,
      such as the PI3K pathway. These findings imply that multiple mechanisms are
      involved in the beneficial effects of soy isoflavone supplements for diabetic
      endothelial injury.

PMID- 19393316
TI  - In vitro hematopoietic differentiation of mouse embryonic stem cells requires the
      tumor suppressor menin and is mediated by Hoxa9.
AB  - Inactivating mutations in the tumor suppressor gene MEN1 cause the inherited
      cancer syndrome multiple endocrine neoplasia type 1 (MEN1). The ubiquitously
      expressed MEN1 encoded protein, menin, interacts with MLL (mixed-lineage leukemia
      protein), and together they are essential components of a multiprotein complex
      with histone methyl transferase activity. MLL is also essential for
      hematopoiesis, and plays a critical role in leukemogenesis via epigenetic
      regulation of Hoxa9 expression that also requires menin. Therefore we chose to
      explore the role of menin in hematopoiesis. We generated Men1(-/-) embryonic stem
      (ES) cell lines, and induced them to differentiate in vitro. While these cells
      were able to form embryoid bodies (EBs) expressing the early markers Flk-1 and c
      Kit, their ability to further differentiate into hematopoietic colonies was
      compromised. The Men1(-/-) ES cells show reduced expression of Hoxa9 that can be
      recovered by reexpression of Menin. We demonstrate that the block in
      differentiation of Men1(-/-) ES cell lines can be rescued not only by the
      expression of menin but also that of Hoxa9. These results suggest that, similar
      to MLL, menin is required for hematopoiesis, and this requirement may be mediated
      through regulation of Hoxa9 expression.

PMID- 19393317
TI  - Bruno negatively regulates germ cell-less expression in a BRE-independent manner.
AB  - Mechanisms of post-transcriptional control are essential during Drosophila
      oogenesis and embryogenesis to sequester gene products in discrete regions and
      ultimately achieve embryonic asymmetry. Maternal germ cell-less (gcl) mRNA
      accumulates in the pole plasm of the embryo before Gcl protein is detectable. gcl
      mRNA, but not Gcl protein, can also be detected in somatic regions of the embryo,
      suggesting that gcl RNA is subject to translational control. We find that Gcl is
      expressed during oogenesis, and that it is regulated by the translational
      repressor Bruno (Bru). Increased levels of Gcl are observed in the oocyte when
      Bru level is reduced, and overexpression of Bru reduces Gcl expression.
      Consistently, reduction of the maternal dosage of Bruno leads to ectopic Gcl
      expression in the embryo, which, in turn, represses anterior huckebein (hkb)
      expression. Bru binds directly to the gcl 3'UTR in vitro, but, surprisingly, this
      binding is independent of a BRE (Bruno response element)-like motif. This motif
      is also not required for in vivo repression of Gcl expression during oogenesis or
      early embryogenesis. Bru binds the gcl 3'UTR via its C-terminal domain, which
      includes RNA recognition motif 3 (RRM3), with little or no contribution from the
      remainder of the protein. We conclude that repression by Bruno during oogenesis
      is required to restrict Gcl expression in the early embryo and that Bru represses
      gcl expression in a manner that involves RRM3 and a sequence unrelated to the
      BRE.

PMID- 19393319
TI  - Expression of Epstein-Barr virus EBNA1 protein in Escherichia coli: purification
      under nondenaturing conditions and use in DNA-binding studies.
AB  - Epstein-Barr virus nuclear antigen 1 (EBNA1) is a viral protein required for
      stable replication and segregation of DNA episomes containing the Epstein-Barr
      virus (EBV) origin of replication, OriP. Overproduction of EBNA1 protein in
      Escherichia coli has previously been shown to be difficult due to the large
      number of codons in EBNA1 gene that are infrequently used in E. coli. Here we
      changed the 26 rare codons that are found among the first 78 codons of EBNA1
      gene, and replaced them with codons that encode the same amino-acids but are
      abundant in E. coli. This led to a significant improvement of EBNA1 expression in
      a standard E. coli strain. Partial EBNA1 polypeptides of 11.5-16 kDa extending
      from the N-terminus to the second arginine and glycine-rich region were extremely
      abundant in the extract, however, resulting in a second limitation of the level
      of EBNA1 expression. EBNA1 was expressed as a fusion with a C-terminal six
      histidine tag in order to get rid of the short polypeptides by Ni-NTA affinity
      purification, and salt conditions were used that allowed us to extract and purify
      EBNA1 without resorting to protein denaturing reagents. The purified protein was
      used in DNA-binding experiments with DNA fragments containing specific EBNA1
      sites. The E. coli-expressed protein formed specific DNA-protein complexes that
      could be analyzed in polyacrylamide gels without showing the aggregation, or
      linking, phenomenon that is usually observed with EBNA1 expressed in eukaryotic
      cells. EBNA1 protein expressed in E. coli should therefore prove useful to
      further study the biochemical properties of this crucial Epstein-Barr virus
      protein.

PMID- 19393318
TI  - Neutrophil elastase and neurovascular injury following focal stroke and
      reperfusion.
AB  - Neutrophil elastase (NE) degrades basal lamina and extracellular matrix
      molecules, and recruits leukocytes during inflammation; however, a basic
      understanding of the role of NE in stroke pathology is lacking. We measured an
      increased number of extravascular NE-positive cells, as well as increased levels
      of tissue elastase protein and activity, following transient middle cerebral
      artery occlusion (tMCAo). Both pharmacologic inhibition of NE with ZN200355 (ZN),
      and genetic deletion of NE, significantly reduced infarct volume, blood-brain
      barrier disruption, vasogenic edema, and leukocyte-endothelial adherence 24 h
      after tMCAo. ZN also reduced infarct volume in MMP9-null mice following tMCAo.
      There were, however, no reductions in infarct volume or vasogenic edema in NE
      null mice in two models of permanent middle cerebral artery occlusion. Our
      findings confirm the involvement of NE in neurovascular stroke pathology, when
      reperfusion allows neutrophils access to vulnerable brain, with pharmacologic or
      genetic inhibition of NE being both neuro- and vasculo-protective in this
      setting.

PMID- 19393320
TI  - Single-trial reconstruction of finger-pinch forces from human motor-cortical
      activation measured by near-infrared spectroscopy (NIRS).
AB  - Near-infrared spectroscopy (NIRS) has recently been used to measure human motor
      cortical activation, enabling the classification of the content of a sensory
      motor event such as whether the left or right hand was used. Here, we advance
      this NIRS application by demonstrating quantitative estimates of multiple sensory
      motor events from single-trial NIRS signals. It is known that different degrees
      of sensory-motor activation are required to generate various hand/finger force
      levels. Thus, using a sparse linear regression method, we examined whether the
      temporal changes in different force levels could be reconstructed from NIRS
      signals. We measured the relative changes in oxyhemoglobin concentrations in the
      bilateral sensory-motor cortices while participants performed an isometric finger
      pinch force production with their thumb and index finger by repeatedly exerting
      one of three target forces (25, 50, or 75% of the maximum voluntary contraction)
      for 12 s. To reconstruct the generated forces, we determined the regression
      parameters from the training datasets and applied these parameters to new test
      datasets to validate the parameters in the single-trial reconstruction. The
      temporal changes in the three different levels of generated forces, as well as
      the baseline resting state, could be reconstructed, even for the test datasets.
      The best reconstruction was achieved when using only the selected NIRS channels
      dominantly located in the contralateral sensory-motor cortex, and with a four
      second hemodynamic delay. These data demonstrate the potential for reconstructing
      different levels of external loads (forces) from those of the internal loads
      (activation) in the human brain using NIRS.

PMID- 19393321
TI  - Estimation of fiber orientation probability density functions in high angular
      resolution diffusion imaging.
AB  - An estimator of the Orientation Probability Density Function (OPDF) of fiber
      tracts in the white matter of the brain from High Angular Resolution Diffusion
      data is presented. Unlike Q-Balls, which use the Funk-Radon transform to estimate
      the radial projection of the 3D Probability Density Function, the Jacobian of the
      spherical coordinates is included in the Funk-Radon approximation to the radial
      integral. Thus, true angular marginalizations are computed, which allows a strict
      probabilistic interpretation. Extensive experiments with both synthetic and real
      data show the better capability of our method to characterize complex micro
      architectures compared to other related approaches (Q-Balls and Diffusion
      Orientation Transform), especially for low values of the diffusion weighting
      parameter.

PMID- 19393322
TI  - Relationship between respiration, end-tidal CO2, and BOLD signals in resting
      state fMRI.
AB  - A significant component of BOLD fMRI physiological noise is caused by variations
      in the depth and rate of respiration. It has previously been demonstrated that a
      breath-to-breath metric of respiratory variation (respiratory volume per time;
      RVT), computed from pneumatic belt measurements of chest expansion, has a strong
      linear relationship with resting-state BOLD signals across the brain. RVT is
      believed to capture breathing-induced changes in arterial CO(2), which is a
      cerebral vasodilator; indeed, separate studies have found that spontaneous
      fluctuations in end-tidal CO(2) (PETCO(2)) are correlated with BOLD signal time
      series. The present study quantifies the degree to which RVT and PETCO(2)
      measurements relate to one another and explain common aspects of the resting
      state BOLD signal. It is found that RVT (particularly when convolved with a
      particular impulse response, the "respiration response function") is highly
      correlated with PETCO(2), and that both explain remarkably similar spatial and
      temporal BOLD signal variance across the brain. In addition, end-tidal O(2) is
      shown to be largely redundant with PETCO(2). Finally, the latency at which
      PETCO(2) and respiration belt measures are correlated with the time series of
      individual voxels is found to vary across the brain and may reveal properties of
      intrinsic vascular response delays.

PMID- 19393323
TI  - Neural encoding of sound duration persists in older adults.
AB  - Speech perception depends strongly on precise encoding of the temporal structure
      of sound. Although behavioural studies suggest that communication problems
      experienced by older adults may entail deficits in temporal acuity, much is
      unknown about the effects of age on the neural mechanisms underlying the encoding
      of sound duration. In this study, we measured neuromagnetic auditory evoked
      responses in young, middle-aged and older healthy participants listening to
      sounds of various durations. The time courses of cortical activity from bilateral
      sources in superior temporal planes showed specific differences related to the
      sound offsets indicating the neural representation of onset and offset markers as
      one dimension of the neural code for sound duration. Model free MEG source
      analysis identified brain areas specifically responding with an increase in
      activity to increases in sound duration in the left anterior insula, right
      inferior frontal, right middle temporal, and right post-central gyri in addition
      to bilateral supra-temporal gyri. Sound duration-related changes in cortical
      responses were comparable in all three age groups despite age-related changes in
      absolute response magnitudes. The results demonstrated that early cortical
      encoding of the temporal structure of sound presented in silence is little or not
      affected by normal aging.

PMID- 19393324
TI  - Development and evolution of the pallium.
AB  - The neocortex is the most representative and elaborated structure of the
      mammalian brain and is related to the achievement of complex cognitive
      capabilities, which are disturbed following malformation or lesion. Searching for
      the evolutionary origin of this structure continues to be one of the most
      important and challenging questions in comparative neurobiology. However, this is
      extremely difficult because of the highly divergent evolution of the pallium in
      different vertebrates, which has obscured the comparison. Herein, we review
      developmental neurobiology data for trying to understand the genetic factors that
      define and underlie the parcellation of homologous pallial subdivisions in
      different vertebrates. According to these data, the pallium in all tetrapods
      parcellates during development into four major histogenetic subdivisions, which
      are homologous as fields across species. The neocortex derives from the dorsal
      pallium and, as such, is only comparable to the sauropsidian dorsal pallium
      (avian hyperpallium and lizard/turtle dorsal cortex). We also tried to identify
      developmental changes in phylogeny that may be responsible of pallial divergent
      evolution. In particular, we point out to evolutionary differences regarding the
      cortical hem (an important signaling center for pallial patterning, that also is
      a source of Cajal-Retzius cells, which are involved in cortical lamination),
      which may be behind the distinct organization of the pallium in mammals and non
      mammals. In addition, we mention recent data suggesting a correlation between the
      appearance and elaboration of the subventricular zone (a new germinative cell
      layer of the developing neocortex), and the evolution of novel cell layers (the
      supragranular layers) and interneuron subtypes. Finally, we comment on epigenetic
      factors that modulate the developmental programs, leading to changes in the
      formation of functional areas in the pallium (within some constraints).

PMID- 19393325
TI  - Interrelation of immunity and tissue repair or regeneration.
AB  - Although tremendous progress has been achieved in understanding the molecular
      basis of tissue repair and regeneration in diverse model organisms, the tendency
      of mammals for imperfect healing and scarring rather than regeneration remains
      unexplained. Moreover, conditions of impaired wound healing, e.g. non-healing
      skin ulcers associated with diabetes mellitus or vascular disease, as well as
      excessive scarring, represent major clinical and socio-economical problems. The
      development of innovative strategies to improve tissue repair and regeneration is
      therefore an important task that requires a more thorough understanding of the
      underlying molecular and cellular mechanisms. There is substantial evidence in
      different model organisms that the immune system is of primary importance in
      determining the quality of the repair response, including the extent of scarring,
      and the restoration of organ structure and function. Findings in diverse species
      support a correlation between the loss of regeneration capacity and maturation of
      immune competence. However, in recent years, there is increasing evidence on
      conditions where the immune response promotes repair and ensures local tissue
      protection. Hence, the relationship between repair and the immune response is
      complex and there is evidence for both negative and positive roles. We present an
      overview on recent evidence that highlights the immune system to be key to
      efficient repair or its failure. First, we summarize studies in different model
      systems that reveal both promoting and impeding roles of the immune system on the
      regeneration and repair capacity. This part is followed by a delineation of
      diverse inflammatory cell types, selected peptide growth factors and their
      receptors as well as signaling pathways controlling inflammation during tissue
      repair. Finally, we report on new mechanistic insights on how these inflammatory
      pathways impair healing under pathological conditions and discuss therapeutic
      implications.

PMID- 19393326
TI  - Assessment of myocardial injury in the emergency department independently
      predicts the short-term poor outcome in patients with severe carbon monoxide
      poisoning receiving mechanical ventilation and hyperbaric oxygen therapy.
AB  - OBJECTIVES: Patients with severe carbon monoxide (CO) poisoning are often prone
      to unconsciousness and respiratory distress and as a result will receive
      mechanical ventilation and hyperbaric oxygen (MV-HBO) therapy. Factors associated
      with poor outcome at discharge are less defined in this patient population. This
      study was conducted to identify the prognostic predictors of short-term poor
      outcome in severely CO-poisoned patients receiving MV-HBO therapy. METHODS: The
      departmental database and the medical records of 81 patients treated with MV-HBO
      therapy were reviewed. Demographic and clinical data were extracted for analysis.
      HBO therapy with 2.5 or 2.8 atmosphere absolute (ATA) was administered to these
      patients. Short-term poor outcome was defined as an in-hospital death or
      neurologic sequelae at discharge. All patients were divided into two groups:
      those with a poor outcome and those without a poor outcome. RESULTS: Nine
      patients died while in the hospital, 32 patients had neurologic sequelae at
      discharge, and the incidence of poor outcome was 50.6%. Parameters that were
      assessed in the emergency department (ED) and highly associated with patients
      with a poor outcome included myocardial injury, typical findings on brain
      computed tomography related to CO poisoning, and higher serum levels of alanine
      transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine,
      creatine kinase, creatine kinase-myocardial band, troponin-I, and C-reactive
      protein. These poor outcomes were also correlated with prolonged lag times from
      the end of CO exposure to ED arrival and from ED arrival to HBO therapy. In a
      multivariate analysis, myocardial injury was the only independent predictor of
      poor outcome (odds ratio, 8.2; 95% confidence interval, 1.012-67.610; p=0.049).
      CONCLUSIONS: The results of this study indicate that myocardial injury assessed
      at ED arrival independently predicts the short-term poor outcome in severely CO
      poisoned patients who receive MV-HBO therapy. Emergency physicians could use this
      objective marker to identify patients with an increased risk of poor outcome at
      discharge and refine the treatment protocol by shortening the time of patient
      transport and administering HBO therapy as soon as possible.

PMID- 19393327
TI  - Relaxant effect of brain natriuretic peptide in nonsensitized and passively
      sensitized isolated human bronchi.
AB  - Brain natriuretic peptide (BNP) relaxes guinea pig tracheal smooth muscle in
      vitro and is effective in preventing ovalbumin-induced bronchoconstriction and
      microvascular leakage in guinea pigs in vivo. Nonetheless, published studies on
      BNP in human airways in vitro are still lacking in the literature. The aim of
      this study was to investigate the effect of BNP in isolated human bronchi. The
      relaxant effect of BNP (1 nM to 10 microM) was assessed in nonsensitized and in
      passively sensitized human bronchial airways pre-contracted with submaximal
      concentration (EC(70)) of carbachol or histamine. At the end of the experiment,
      papaverine (500 microM) was then added. BNP induced a weak relaxant activity on
      carbachol-contracted bronchi in nonsensitized (relaxation: 4.23+/-0.51%) and
      passively sensitized bronchi (relaxation: 11.31+/-2.22%). On the other hand, BNP
      induced a relaxant activity on His-contracted bronchi in nonsensitized
      (relaxation: 42.52+/-9.03%) and in passively sensitized (relaxation: 60.57+/
      9.58%). All these findings are a clear documentation of the modest relaxant role
      of BNP in asthma and, likely, COPD.

PMID- 19393328
TI  - N-acetyl-L-cysteine inhibits TGF-beta1-induced profibrotic responses in
      fibroblasts.
AB  - BACKGROUND: Excessive production of TGF-beta(1) plays a key role in the tissue
      remodeling or fibrotic process observed in bronchial asthma, chronic pulmonary
      disease (COPD), and idiopathic pulmonary fibrosis (IPF). TGF-beta(1) has been
      reported to decrease the intracellular glutathione level and stimulate the
      production of reactive oxygen species. OBJECTIVES: The aim of this study was to
      evaluate whether the antioxidant N-acetyl-l-cysteine (NAC) can affect TGF-beta(1)
      mediated tissue remodeling in fibroblasts or modulate the production of
      fibronectin and vascular endothelial growth factor (VEGF) which are believed to
      be important mediators of tissue repair and remodeling. METHODS: To accomplish
      this, human fetal lung fibroblasts (HFL-1) were used to assess the effect of NAC
      on the TGF-beta(1)-mediated contraction of floating gels and the TGF-beta(1)
      induced mediator production. In addition, the effect of NAC on the TGF-beta(1)
      induced differentiation to myofibroblasts was evaluated by assessing alpha-smooth
      muscle actin (alpha-SMA) expression. RESULTS: NAC significantly abolished the TGF
      beta(1)-augmented gel contraction (at 3mM, gel size 63.4+/-2.6% vs. 39.1+/-4.1%;
      p<0.01) compared with control in a concentration-dependent manner. NAC also
      significantly inhibited the TGF-beta(1)-augmented fibronectin (p<0.01) and VEGF
      (p<0.01) production in the media of both the three-dimensional gel and monolayer
      culture. Furthermore, NAC reversed the TGF-beta(1)-stimulated alpha-SMA
      expression (p<0.01). CONCLUSION: These results suggest that NAC can affect the
      TGF-beta(1)-induced tissue remodeling or fibrotic process in vitro.

PMID- 19393329
TI  - A low concentration of azithromycin inhibits the mRNA expression of N-acyl
      homoserine lactone synthesis enzymes, upstream of lasI or rhlI, in Pseudomonas
      aeruginosa.
AB  - Low-dose macrolides are effective therapy in patients with chronic lung
      infections, but the mechanisms of action are unclear. In this study, we performed
      DNA microarray analysis of Pseudomonas aeruginosa after treatment with a low
      concentration of azithromycin. We found that a sub-MIC of azithromycin didn't
      change mRNA expression of quorum-sensing related genes (lasI, lasR, rhlI, rhlR,
      vft, rsaL), but lowered expression of most N-acyl homoserine lactone (AHL)
      synthesis enzymes upstream of lasI and rhlI. We propose that small down
      regulation of these enzymes cumulatively resulted in a larger decrease of AHL
      production and inhibition of quorum-sensing in P. aeruginosa.

PMID- 19393331
TI  - Functional differential immune responses of Mytilus galloprovincialis to
      bacterial challenge.
AB  - Bivalves are filter-feeders that can accumulate large numbers of bacteria, in
      particular Vibrio species; these can persist within bivalve tissues largely
      depending on their sensitivity to the hemolymph bactericidal activity. In this
      work, functional parameters of the hemolymph of Mytilus galloprovincialis were
      evaluated in response to in vivo challenge with different bacteria (Gram(-)
      Vibrio anguillarum and V. splendidus, Gram+ Micrococcus lysodeikticus). Mussels
      were injected with heat-killed bacteria or PBS-NaCl (controls) and hemolymph
      sampled from 3 to 48 h post-injection (p.i.). In hemocytes, all bacteria induced
      significant lysosomal membrane destabilisation (LMS) from 3 h p.i. with V.
      splendidus >V. anguillarum >M. lysodeikticus. LMS showed recovery for both M.
      lysodeikticus and V. anguillarum, whereas a further time-dependent decrease was
      observed for V. splendidus. Bacterial challenge also induced a rapid (from 3 h
      p.i.) and significant increase in serum lysozyme activity; the effect was
      persistent with M. lysodeikticus and transient for the two Vibrio species. In
      order to evaluate whether in vivo challenge may affect the subsequent capacity of
      hemolymph to kill bacteria, the bactericidal activity was tested in an in vitro
      assay towards E. coli. At 48 h. p.i. hemolymph samples from V. anguillarum
      injected mussels showed a significant increase in E. coli killing (+35% with
      respect to controls); a smaller effect was observed with V. splendidus-injected
      mussels (+16%), whereas M. lysodeikticus was ineffective. Moreover, hemolymph
      from V. anguillarum-injected mussels showed an in vitro bactericidal activity
      towards V. anguillarum 2-folds higher than that of controls. Changes in total
      hemocyte counts (THC) and in hemocyte populations were evaluated by Flow
      cytometry at 6 and 48 h p.i., indicating a decrease in THC followed by recovery
      with all bacteria. Moreover, at 6 h p.i. a general decrease in the percentage of
      granulocytes was observed (V. splendidus >V. anguillarum >M. lysodeikticus),
      followed by complete and partial recovery with M. lysodeikticus and V.
      anguillarum, respectively, but not with V. splendidus. The results demonstrate
      the existence of differential functional immune responses in M. galloprovincialis
      to different bacteria.

PMID- 19393330
TI  - Transcriptional regulation of cytokine function in airway smooth muscle cells.
AB  - The immuno-modulatory properties of airway smooth muscle have become of
      increasing importance in our understanding of the mechanisms underlying chronic
      inflammation and structural remodeling of the airway wall in asthma and chronic
      obstructive pulmonary disease (COPD). ASM cells respond to many cytokines, growth
      factors and lipid mediators to produce a wide array of immuno-modulatory
      molecules which may in turn orchestrate and perpetuate the disease process in
      asthma and COPD. Despite numerous studies of the cellular effects of cytokines on
      cultured ASM, few have identified intracellular signaling pathways by which
      cytokines modulate or induce these cellular responses. In this review we provide
      an overview of the transcriptional mechanisms as well as intracellular signaling
      pathways regulating cytokine functions in ASM cells. The recent discovery of toll
      like receptors in ASM cells represents a significant development in our
      understanding of the immuno-modulatory capabilities of ASM cells. Thus, we also
      review emerging evidence of the inflammatory response to toll-like receptor
      activation in ASM cells.

PMID- 19393333
TI  - Cytotoxicity and chromosomal aberrations induced by acrylamide in V79 cells: role
      of glutathione modulators.
AB  - Acrylamide (AA) is a suspected human carcinogen found to be generated during the
      heating of carbohydrate-rich foodstuffs. AA exhibits 'Michael-type' reactivity
      towards reduced glutathione (GSH), resulting in vivo in the urinary excretion of
      mercapturic acid conjugates. GSH is a key factor for mammalian cell homeostasis,
      with diverse functions that include, among others, the conjugation of
      electrophilic compounds and the detoxification of products generated by oxidative
      stress. Therefore, studies focusing on the modulation of GSH are of great
      importance for the understanding of the mechanisms of AA-induced toxicity. This
      report addresses this issue by analyzing cytotoxicity (3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay) and clastogenicity
      (chromosomal aberrations) as endpoints in V79 cells after exposure to AA. The
      experiments described herein include the evaluation of the effect of buthionine
      sulfoximine (BSO), an effective inhibitor of GSH synthesis, GSH-monoethyl ester
      (GSH-EE), a compound that is taken up by cells and intracellularly hydrolysed to
      GSH, and also GSH exogenously added to culture medium. Pre-treatment with BSO
      increased the cytotoxicity and the frequency of aberrant cells excluding gaps
      (ACEG) induced by AA. While pre-treatment with GSH-EE did not modify the
      cytotoxicity or the frequency of ACEG induced by AA, co-treatment with AA and GSH
      decreased both parameters, rendering the cells less prone to the toxic effects of
      AA. In vitro studies in a cell-free system, using monochlorobimane (MCB), a
      fluorescent probe for GSH, were also performed in order to evaluate the role of
      AA in GSH depletion. The results show that spontaneous conjugation of AA with GSH
      in the extracellular medium is involved in the protection given by GSH. In
      summary, these results reinforce the role of GSH in the modulation of the
      cytotoxic and clastogenic effects induced by AA, which may be relevant in an in
      vivo exposure scenario.

PMID- 19393332
TI  - Prostaglandin E2 synthases in neurologic homeostasis and disease.
AB  - Prostaglandin E(2) synthases (PGES) currently comprise a group of three
      structurally and biologically distinct molecules. These enzymes are part of an
      important and complex paracrine signaling system involved in a wide range of
      biological processes. This review focuses on the normal physiological and
      pathological roles of these enzymes in the nervous system. Specific topics
      include the role of PGES(s) in fever and sickness behavior, inflammatory pain,
      and neural disease. Although the field is in its early stages, ongoing
      development of selective PGES inhibitors for possible use in people creates a
      significant need for more fully understanding the biological roles of these
      important enzymes.

PMID- 19393334
TI  - Thresholds for genotoxins and their application in risk assessment.

PMID- 19393335
TI  - Evaluation of the Vitotox and RadarScreen assays for the rapid assessment of
      genotoxicity in the early research phase of drug development.
AB  - The Vitotox and RadarScreen assays were evaluated as early screens for
      mutagenicity and clastogenicity, respectively. The Vitotox assay is a bacterial
      reporter assay in Salmonella typhimurium based on the SOS-response, and it
      contains a luciferase gene under control of the recN promoter. The RadarScreen
      assay is a RAD54 promoter-linked beta-galactosidase reporter assay in yeast. The
      expression of this beta-galactosidase can easily be quantified by use of the
      substrate d-luciferin-o-beta-galactopyranoside, which is converted into galactose
      and luciferin that can be measured luminometrically. Recently, an ECVAM workgroup
      defined a list of 20 genotoxic and 42 non-genotoxic compounds [D. Kirkland, P.
      Kasper, L. Muller, R. Corvi, G. Speit, Recommended lists of genotoxic and non
      genotoxic chemicals for assessment of the performance of new or improved
      genotoxicity tests: a follow-up to an ECVAM workshop, Mutat. Res. 653 (2008) 99
      108.] that can be used for the validation and/or optimization of in vitro
      genotoxicity assays. In the present study, this compound set was used for the
      validation of the assays. Moreover, an additional set of 192 compounds was used
      to broaden this validation study. The compounds of this additional set can be
      classified as non-genotoxins and genotoxins and consists of both in-house and
      reference compounds. In case of the ECVAM compound list, the results from the
      Vitotox and RadarScreen assays were compared to the genotoxic/non-genotoxic
      classification of the compounds in this list. In case of the additionally tested
      compounds, the results of the Vitotox and RadarScreen assays were compared,
      respectively, with bacterial mutagenicity (Ames) results or in vitro
      clastogenicity data obtained in-house or from the literature. The validation with
      respect to the ECVAM compound list resulted in a sensitivity for both the Vitotox
      and RadarScreen assay of 70% (14/20). If both assays were combined the
      sensitivity increased to 85% (17/20). Both tests also gave a low number of false
      positive results. The specificity of the Vitotox and RadarScreen assays was 93%
      (39/42) and 83% (35/42), respectively. This resulted in a predictivity of the
      Vitotox and RadarScreen assay of 85% (53/62) and 79% (49/62), respectively. In
      case both tests were combined the specificity and the predictivity of the Vitotox
      and RadarScreen assay turned out to be 81% (34/42) and 82% (51/62), respectively.
      The results from the additional list of 192 compounds confirmed the results found
      with the ECVAM compound list. The results from the Vitotox assay showed a high
      correlation with Ames test of 91% (132/145). Subsequently, the RadarScreen assay
      had a correlation with in vitro clastogenicity of 76% (93/123). The specificity
      of the Vitotox assay was 94% (90/96) for Ames test results and that of the
      RadarScreen assay was 74% (34/46) for clastogenicity. Moreover, the sensitivities
      of the Vitotox and RadarScreen assays were 86% (42/49) and 77% (59/77),
      respectively. Implementation of the Vitotox and RadarScreen assays in the early
      research phase of drug development can lead to fast de-selection for
      genotoxicity. It is expected that this application will reduce the number of
      compounds that have a positive score in the regulatory Ames and clastogenicity
      tests. Moreover, problems with a complete compound class can be foreseen at an
      early time point in the research phase, which gives more time for issue
      resolution than late detection of these problems with the regulatory tests.

PMID- 19393336
TI  - Species-level differences between mice and rats in regards to micronucleus
      induction with the hypothermia-inducing drug haloperidol.
AB  - Species-level differences in response to micronucleus induction with haloperidol,
      a drug that can induce hypothermia, were investigated. Haloperidol was
      intraperitoneally (i.p.) administered to mice (12.5-50 mg/kg) and rats (25-100
      mg/kg), and the rectal temperature was then measured. At every investigated dose,
      haloperidol transiently decreased the rectal temperature in mice to less than 30
      degrees C. However, the rectal temperature decreased to approximately 34 degrees
      C in rats. For micronucleus induction, haloperidol at doses of 25 and 50 mg/kg
      resulted in a statistically significant increase in micronucleated polychromatic
      erythrocyte frequency in the 48 h sampling group of mice, but not in rats. In
      addition, relatively large micronuclei (diameter of micronucleus > one-fourth the
      diameter of the cytoplasm) accounted for 46-47% of the induced micronuclei in
      mice, suggesting that hypothermia affected the mitotic apparatus. Thus,
      hypothermia can induce micronuclei in vivo as a secondary effect, and the
      hypothermic response to haloperidol in mice was stronger than that of rats.
      Micronuclei could only be induced in mice during this study. Therefore, species
      level differences may exist in regards to micronucleus induction by hypothermia
      inducing drugs.

PMID- 19393337
TI  - Cytogenetic evaluation for genotoxicity of bisphenol-A in bone marrow cells of
      Swiss albino mice.
AB  - Bisphenol-A (BP-A) is a xenobiotic estrogenic compound used in a wide range of
      consumer products. BP-A was tested for its genotoxicity by employing three
      cytogenetic assays, viz., chromosomal aberration test, micronucleus assay and
      test for c-mitotic effects in Swiss albino mice. Studies were carried out for
      three doses, 10, 50 and 100 mg/kg in single oral exposure and 10 mg/kg in
      repeated oral exposure (for 5 days). It is evident from the present investigation
      that although BP-A failed to induce conventional chromosomal aberrations and
      micronuclei, its genotoxic potential was manifested in the form of achromatic
      lesion and c-mitotic effects in the bone marrow cells. It can also be speculated
      from the results that the threshold concentration of BP-A required for the
      formation of MN is much higher than that for the induction of c-mitotic effects.

PMID- 19393340
TI  - Using UMLS to construct a generalized hierarchical concept-based dictionary of
      brain functions for information extraction from the fMRI literature.
AB  - With a rapid progress in the field, a great many fMRI studies are published every
      year, to the extent that it is now becoming difficult for researchers to keep up
      with the literature, since reading papers is extremely time-consuming and labor
      intensive. Thus, automatic information extraction has become an important issue.
      In this study, we used the Unified Medical Language System (UMLS) to construct a
      hierarchical concept-based dictionary of brain functions. To the best of our
      knowledge, this is the first generalized dictionary of this kind. We also
      developed an information extraction system for recognizing, mapping and
      classifying terms relevant to human brain study. The precision and recall of our
      system was on a par with that of human experts in term recognition, term mapping
      and term classification. Our approach presented in this paper presents an
      alternative to the more laborious, manual entry approach to information
      extraction.

PMID- 19393338
TI  - Lipid aldehyde-mediated cross-linking of apolipoprotein B-100 inhibits secretion
      from HepG2 cells.
AB  - Hepatic oxidative stress and lipid peroxidation are common features of several
      prevalent disease states, including alcoholic liver disease (ALD) and non
      alcoholic fatty liver disease (NAFLD), a common component of the metabolic
      syndrome. These conditions are characterized in part by excessive accumulation of
      lipids within hepatocytes, which can lead to autocatalytic degradation of
      cellular lipids giving rise to electrophilic end products of lipid peroxidation.
      The pathobiology of reactive lipid aldehydes remains poorly understood. We
      therefore sought to investigate the effects of 4-hydroxynonenal (4-HNE) and 4
      oxononenal (4-ONE) on the transport and secretion of very low-density lipoprotein
      using HepG2 cells as a model hepatocyte system. Physiologically relevant
      concentrations of 4-HNE and 4-ONE rapidly disrupted cellular microtubules in a
      concentration-dependent manner. Interestingly, 4-ONE reduced apolipoprotein B-100
      (ApoB) secretion while 4-HNE did not significantly impair secretion. Both 4-HNE
      and 4-ONE formed adducts with ApoB protein, but 4-HNE adducts were detectable as
      mono-adducts, while 4-ONE adducts were present as protein-protein cross-links.
      These results demonstrate that reactive aldehydes generated by lipid peroxidation
      can differ in their biological effects, and that these differences can be
      mechanistically explained by the structures of the protein adducts formed.

PMID- 19393339
TI  - Increased de novo lipogenesis in liver contributes to the augmented fat
      deposition in dexamethasone exposed broiler chickens (Gallus gallus domesticus).
AB  - Effect of dexamethasone (DEX, a synthetic glucocorticoid) on lipid metabolism in
      broiler chickens (Gallus gallus domesticus) was investigated. Male Arbor Acres
      chickens (1 wk old, n=30) were injected with DEX or saline for 1 wk, and a pair
      fed group was included. DEX administration resulted in enhanced lipid deposition
      in adipose tissues. Plasma insulin increased about 3.3 fold in DEX injected
      chickens as against the control and hepatic triglyceride was higher as compared
      with the pair-fed chickens. In DEX injected chickens, the hepatic activities of
      malic enzyme (ME) and fatty acid synthetase (FAS) were significantly increased,
      while the mRNA levels of acetyl CoA carboxylase (ACC), ME, and FAS were
      significantly up-regulated, compared with the control. Although the mRNA levels
      of lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-gamma
      (PPARgamma) and adipose triglyceride lipase (ATGL) genes in adipose tissue were
      not affected by DEX injection, ME activity and mRNA levels in abdominal fat pad
      of chickens treated with DEX are higher than those of control chickens. The
      results indicated that the increased hepatic de novo lipogenesis and in turn, the
      increased circulating lipid flux contributes to the augmented fat deposition in
      adipose tissues and liver in DEX-challenged chickens. The results suggest that
      glucocorticoids together with the induced hyperinsulinemia should be responsible
      for the up-regulated hepatic lipogenesis.

PMID- 19393341
TI  - @Note: a workbench for biomedical text mining.
AB  - Biomedical Text Mining (BioTM) is providing valuable approaches to the automated
      curation of scientific literature. However, most efforts have addressed the
      benchmarking of new algorithms rather than user operational needs. Bridging the
      gap between BioTM researchers and biologists' needs is crucial to solve real
      world problems and promote further research. We present @Note, a platform for
      BioTM that aims at the effective translation of the advances between three
      distinct classes of users: biologists, text miners and software developers. Its
      main functional contributions are the ability to process abstracts and full
      texts; an information retrieval module enabling PubMed search and journal
      crawling; a pre-processing module with PDF-to-text conversion, tokenisation and
      stopword removal; a semantic annotation schema; a lexicon-based annotator; a user
      friendly annotation view that allows to correct annotations and a Text Mining
      Module supporting dataset preparation and algorithm evaluation. @Note improves
      the interoperability, modularity and flexibility when integrating in-home and
      open-source third-party components. Its component-based architecture allows the
      rapid development of new applications, emphasizing the principles of transparency
      and simplicity of use. Although it is still on-going, it has already allowed the
      development of applications that are currently being used.

PMID- 19393342
TI  - Chronic epigallocatechin-gallate improves aortic reactivity of diabetic rats:
      underlying mechanisms.
AB  - Diabetes mellitus is associated with major cardiovascular risk factors which are
      responsible for excess morbidity and mortality. Green tea catechins including
      epigallocatechin-3-gallate (EGCG) could exert beneficial health effects to
      ameliorate cardiovascular and metabolic diseases. Thus, the effect of chronic
      administration of EGCG was studied on aortic reactivity of streptozotocin (STZ)
      diabetic rats. Male diabetic rats received EGCG 25 mg/kg/day for 8 weeks 1 week
      after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and
      relaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were
      obtained from aortic rings. Maximum contractile response of endothelium-intact
      rings to KCL and PE was significantly lower in EGCG-treated diabetic rats
      relative to untreated diabetic ones. Endothelium removal abolished the
      significant difference between EGCG-treated and untreated diabetic groups
      regarding contractile response to KCl and PE. Meanwhile, endothelium-dependent
      relaxation to ACh was significantly higher in EGCG-treated diabetic rats as
      compared to diabetic ones. Pretreatment of rings with N(omega)-L-arginine methyl
      ester (L-NAME) and indomethacin (INDO) significantly attenuated the observed
      responses. Meanwhile, two-month diabetes resulted in an elevation of
      malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity in aortic
      tissue and EGCG treatment attenuated the increased MDA content and reduced
      activity of SOD. Therefore, chronic treatment of diabetic rats with EGCG could
      prevent the abnormal functional changes in vascular reactivity in diabetic rats
      through nitric oxide- and prostaglandin-dependent pathways and via attenuation of
      aortic lipid peroxidation.

PMID- 19393343
TI  - BMP and BMP receptor expression during murine organogenesis.
AB  - Cell-cell communication is critical for regulating embryonic organ growth and
      differentiation. The Bone Morphogenetic Protein (BMP) family of transforming
      growth factor beta (TGFbeta) molecules represents one class of such cell-cell
      signaling molecules that regulate the morphogenesis of several organs. Due to
      high redundancy between the myriad BMP ligands and receptors in certain tissues,
      it has been challenging to address the role of BMP signaling using targeting of
      single Bmp genes in mouse models. Here, we present a detailed study of the
      developmental expression profiles of three BMP ligands (Bmp2, Bmp4, Bmp7) and
      three BMP receptors (Bmpr1a, Bmpr1b, and BmprII), as well as their molecular
      antagonist (noggin), in the early embryo during the initial steps of murine
      organogenesis. In particular, we focus on the expression of Bmp family members in
      the first organs and tissues that take shape during embryogenesis, such as the
      heart, vascular system, lungs, liver, stomach, nervous system, somites and limbs.
      Using in situ hybridization, we identify domains where ligand(s) and receptor(s)
      are either singly or co-expressed in specific tissues. In addition, we identify a
      previously unnoticed asymmetric expression of Bmp4 in the gut mesogastrium, which
      initiates just prior to gut turning and the establishment of organ asymmetry in
      the gastrointestinal tract. Our studies will aid in the future design and/or
      interpretation of targeted deletion of individual Bmp or Bmpr genes, since this
      study identifies organs and tissues where redundant BMP signaling pathways are
      likely to occur.

PMID- 19393344
TI  - Tuberculin sensitivity and morphological immune response in guinea pigs after
      application of minimal sensitizing dose of BCG vaccine, substrain Sofia SL222.
AB  - During the investigation of the BCG allergenic potency it is advisable to
      vaccinate with decreasing doses, estimating the lowest dose that induces
      tuberculin sensitivity and specific morphological inflammation. Although the
      biological test does not reveal the mathematical correlation of dose-effect
      relationships, it is important to look for the determination of the minimal
      sensitizing dose for every BCG vaccine. In this study, three groups of twenty
      four guinea pigs were vaccinated with decreasing doses of reconstituted BCG
      vaccine: 120 ng, 12 ng and 1.2 ng. Tuberculin tests were performed in different
      groups at the 30th, 60th, 90th and 120th day after BCG injection. The negative
      tuberculin reactions converted to positive between the 60th and 90th day. The
      dose of 12 ng elicited the largest tuberculin reactions in the animals. This dose
      contains 65 viable bacteria and could be regarded as the smallest effective
      sensitizing dose of the BCG vaccine, substrain Sofia SL222. The morphological
      examination demonstrated that very low inoculums (1.2 ng or 6 viable cells) were
      sufficient to induce a specific inflammation after BCG vaccination. The immune
      response in lungs and bronchus-associated lymphoid tissue (BALT) of all BCG doses
      applied was strongest on the day 60. In the same term, lymph nodes and spleens
      were characterized with blast transformed lymphoid follicles with epitheloid and
      Langhans giant cells even with the smallest injected dose of 1.2 ng.

PMID- 19393346
TI  - Oxyanion and tetrahedral intermediate stabilisation by subtilisin: detection of a
      new tetrahedral adduct.
AB  - The peptide-derived glyoxal inhibitor Z-Ala-Ala-Phe-glyoxal has been shown to be
      approximately 10 fold more effective as an inhibitor of subtilisin than Z-Ala-Pro
      Phe-glyoxal. Signals at 107.2 ppm and 200.5 ppm are observed for the glyoxal keto
      and aldehyde carbons of the inhibitor bound to subtilisin, showing that the
      glyoxal keto and aldehyde carbons are sp(3) and sp(2) hybridised respectively.
      The signal at 107.2 ppm from the carbon atom attached to the hemiketal oxyanion
      is formed in a slow exchange process that involves the dehydration of the glyoxal
      aldehyde carbon. Two additional signals are observed one at 108.2 ppm and the
      other at 90.9 ppm for the glyoxal keto and aldehyde carbons respectively at pHs 6
      8 demonstrating that subtilisin forms an additional tetrahedral adduct with Z-Ala
      Ala-Phe-glyoxal in which both the glyoxal keto and aldehyde carbons are sp(3)
      hybridised. For the first time we can quantify oxyanion stabilisation in
      subtilisin. We conclude that oxyanion stabilisation is more effective in
      subtilisin than in chymotrypsin. Using (1)H-NMR we show that the binding of Z-Ala
      Ala-Phe-glyoxal to subtilisin raises the pK(a) of the imidazolium ion of the
      active site histidine residue promoting oxyanion stabilisation. The mechanistic
      significance of these results is discussed.

PMID- 19393345
TI  - The ectopic expression of IFN regulatory factor 4-binding protein is correlated
      with the malignant behavior of human breast cancer cells.
AB  - Many proteins that are aberrantly expressed in malignant tumors play important
      roles in promoting tumorigenesis, metastasis and immune escape. IFN regulatory
      factor 4-binding protein (IBP), which is a novel PH-DH-like protein related to
      SWAP-70, and functions as an upstream activator of Rho GTPases. It is widely
      expressed in cells of the immune system and is involved in coupling activated
      cell receptors to downstream signaling events that mediate cell proliferation,
      differentiation and polarization. Although IBP was detected in human
      chondrosarcoma, its function in tumor cells remains unknown. In this study, newly
      generated monoclonal anti-IBP antibodies were employed and they detected higher
      level expression of IBP in some human invasive breast carcinoma tissues and in
      two breast cancer cell lines that form highly invasive tumors in nude mice. In
      contrast, the levels of IBP mRNA and protein were low or undetectable in normal
      human breast tissues, benign breast lesions or low-tumorigenic breast cancer cell
      lines. Over-expression of wild-type IBP in an IBP-negative breast cancer cell
      line markedly increased its proliferation and invasiveness in vitro. Conversely,
      RNA interference-mediated knockdown of IBP expression in an IBP-positive breast
      cancer cell line significantly reduced cell growth and invasiveness. Our results
      indicate that IBP is expressed in more highly invasive human breast cancer cells,
      such as MCF-7 and MDA-MB-231, with lower expression in normal breast tissue,
      benign tumors and less aggressive breast cancer cells, such as SKBR3 and MDA-MB
      453. Thus, expression of IBP is correlated with the degree of malignant breast
      tumors. Nevertheless, it should be pointed our that further study with more tumor
      types is required to fully elucidate the role of IBP in tumorigenesis and the
      potential of IBP as a marker for more highly malignant tumors.

PMID- 19393347
TI  - Relationships of acylated and des-acyl ghrelin levels to bone mineralization in
      obese children and adolescents.
AB  - AIMS: Bodyweight is a significant predictor of bone mass. Hormonal factors are
      thought to play a role in the mechanisms controlling the association of body
      weight and fat mass with bone mass. Very recently, the orexigenic hormone ghrelin
      has also been implicated in bone metabolism. In this study we examined the
      associations of circulating acylated and des-acyl ghrelin concentrations with
      measures of bone in a group of obese children and adolescents as well as in a
      group of healthy control children. We also determined whether the associations
      were independent of body composition, chronological age, gender, Tanner stage,
      and leptin, glucose, insulin and insulin-like growth factor (IGF)-1 levels.
      METHODS: We performed a prospective cross-sectional study of 100 obese children
      [age, 8.9 (8.3 to 9.4); BMI-Standard Deviation Score (SDS), 2.2 (2.0 to 2.3)],
      and 100 age-matched lean healthy subjects. Fasting insulin, leptin, IGF-1,
      acylated and total ghrelin were measured by radioimmunoassay. Des-acyl ghrelin
      values were calculated as total ghrelin minus acylated ghrelin. Whole body (WB)
      and lumbar spine (LS) BMD, and BMC as well as body composition were assessed by
      DXA (Hologic QDR-4500W). LS volumetric BMD (BMAD) was estimated using the formula
      of Katzman (BMC/area(1.5)), while WB BMC data were expressed as BMC/height.
      RESULTS: Backward linear regression analysis was performed for individual groups,
      with age, gender, Tanner stage, weight, height, body composition (lean and fat
      mass), acylated ghrelin, des-acyl ghrelin, leptin, glucose, insulin, and IGF-1,
      entered into the model. In healthy children, acylated ghrelin was a significant
      and independent negative predictor of WB BMD, and WB BMC/height, while lean mass
      was positively associated significantly with these bone measures. In contrast, in
      obese children, a positive significant association was observed between des-acyl
      ghrelin and WB BMD as well as WB BMC/height, along with lean mass, and to a
      lesser degree, with fat mass. Acylated as well as des-acyl ghrelin were not
      significant predictors of LS BMD and LS BMAD in obese as well as control
      children. CONCLUSIONS: The results of this investigation indicate that the
      influence of the two distinct isoforms of ghrelin on BMD is mediated by specific
      body composition parameters in obese and control healthy children.

PMID- 19393348
TI  - Historian's address: When the Space Needle was new: recollections of surgery and
      Seattle in the era of century 21.

PMID- 19393349
TI  - A high ratio of plasma and platelets to packed red blood cells in the first 6
      hours of massive transfusion improves outcomes in a large multicenter study.
AB  - BACKGROUND: In trauma, most hemorrhagic deaths occur within the first 6 hours.
      This study examined the effect on survival of high ratios of fresh frozen plasma
      (FFP) and platelets (PLTs) to packed red blood cells (PRBCs) in the first 6
      hours. METHODS: Records of 466 massive transfusion trauma patients (>or=10 U of
      PRBCs in 24 hours) at 16 level 1 trauma centers were reviewed. Transfusion ratios
      in the first 6 hours were correlated with outcome. RESULTS: All groups had
      similar baseline characteristics. Higher 6-hour ratios of FFP:PRBCs and
      PLTs:PRBCs lead to improved 6-hour mortality (from 37.3 [in the lowest ratio
      group] to 15.7 [in the middle ratio group] to 2.0% [in the highest ratio group]
      and 22.8% to 19.0% to 3.2%, respectively) and in-hospital mortality (from 54.9 to
      41.1 to 25.5% and 43.7% to 46.8% to 27.4%, respectively). Initial higher ratios
      of FFP:PRBCs and PLTs:PRBCs decreased overall PRBC transfusion. CONCLUSIONS: The
      early administration of high ratios of FFP and platelets improves survival and
      decreases overall PRBC need in massively transfused patients. The largest
      difference in mortality occurs during the first 6 hours after admission,
      suggesting that the early administration of FFP and platelets is critical.

PMID- 19393350
TI  - The impact of advanced age on trauma triage decisions and outcomes: a statewide
      analysis.
AB  - BACKGROUND: Physiologic variables used in trauma triage criteria may be
      significantly affected by age, decreasing their predictive value in geriatric
      trauma. METHODS: The study population was all adult patients in the Washington
      State Trauma Registry from 2000 to 2004. Elderly patients were defined as those
      aged >65 years. Multivariate analyses were conducted to evaluate the relationship
      between age and trauma triage decisions, need for emergent interventions, and
      outcomes. RESULTS: Of 51,227 trauma admissions, 13,820 (27%) were for elderly
      patients. Elderly patients were significantly less likely to have trauma team
      activation (14% vs 29%, P <.01), despite a similar percentage of severe injuries
      (injury severity score > 15), and more often required urgent craniotomy (10% vs
      6%, P <.01) and orthopedic procedures (67% vs 51%, P <.01). Heart rate and blood
      pressure were not predictive of severe injury for those aged >65 years.
      Undertriaged elderly patients had 4 times the mortality rate and discharge
      disability of younger patients (both P values <.001). CONCLUSIONS: Elderly trauma
      victims are less likely to undergo rapid trauma evaluation and have significantly
      worse outcomes compared with younger patients. Standard physiologic triage
      variables may not identify severe injury in older patients.

PMID- 19393351
TI  - A highly porous silica and chitosan-based hemostatic dressing is superior in
      controlling hemorrhage in a severe groin injury model in swine.
AB  - BACKGROUND: This study compared the efficacy of 3 hemostatic dressings in a
      severe groin injury model in swine. METHODS: Twenty-three swine received
      TraumaStat (OreMedix, Lebanon, OR), Chitoflex (HemCon, Inc., Portland, OR), or
      standard gauze for hemostasis. Complete femoral vessel transections were followed
      by 30 seconds of uncontrolled hemorrhage. The groin was packed with the
      randomized dressing followed by 30 seconds of compression. Resuscitation with
      lactated Ringer's solution commenced immediately postcompression to the preinjury
      mean arterial blood pressure. Hemostasis failure was defined as blood pooling
      outside the wound. Animals were monitored and maintained at the preinjury mean
      arterial pressure for 120 minutes, culminating with euthanization. RESULTS: There
      were no differences in baseline values between groups. TraumaStat resulted in
      less hemostasis failure (P < .05), decreased postcompression blood loss (P <
      .05), and decreased fluid requirement (P < .05). No significant difference in
      mortality was seen between groups. There were no differences between standard
      gauze and Chitoflex with respect to dressing failure, posttreatment blood loss,
      or fluid resuscitation. CONCLUSIONS: TraumaStat performed significantly better
      than Chitoflex and standard gauze in controlling hemorrhage from a severe groin
      injury in swine.

PMID- 19393352
TI  - Reconstruction of complex abdominal wall hernias using acellular human dermal
      matrix: a single institution experience.
AB  - BACKGROUND: Acellular human dermal matrix (AHDM) has mechanical properties
      suitable for complex abdominal wall reconstructions and physiologic properties
      that allow more resistance to infection in contaminated fields. The purpose of
      this study was to determine which patient and technical factors lead to optimal
      surgical outcomes. METHODS: A retrospective review was conducted of 144 abdominal
      wall reconstructions using AHDM over a 33-month period. Data were recorded and
      analyzed. RESULTS: Fifty-three percent were women. The average age was 55 years,
      with an average body mass index of 35 kg/m(2). Thirty percent were smokers at the
      time of repair, and 24% had diabetes. Forty-three percent of the operative fields
      had some degree of contamination. The indication for operation in half the
      patients was to reconstruct a previously failed hernia repair. The recurrence
      rate was 27.1%. The significant factors that affected the recurrence rate were
      female gender (P = .02), reconstructing a failed prior repair (P = .025), and
      high body mass index (P = .004). An underlay mesh placement trended to a lower
      recurrence rate (P = .053). Average follow-up time was 23 weeks (range, 0-100
      weeks). CONCLUSIONS: Three patient factors contributed significantly to the
      recurrence rate in this study: gender, above-normal body mass index, and
      repairing a recurrent hernia. Placing the matrix as an underlay appears to
      decrease recurrence rates. Long-term follow-up is needed to further determine the
      durability of hernia repairs with AHDM. AHDM offers a viable option with
      acceptable morbidity in complex abdominal wall reconstructions in high-risk
      patient populations.

PMID- 19393354
TI  - Phase II study of regional treatment for peritoneal carcinomatosis.
AB  - BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy
      and early postoperative intraperitoneal chemotherapy is becoming an accepted
      treatment of carcinomatosis. METHODS: Between February 2000 and January 2008,
      there were 101 consecutive patients with carcinomatosis who were treated with
      cytoreductive surgery + hyperthermic intraperitoneal chemotherapy and early
      postoperative intraperitoneal chemotherapy. Patient and tumor characteristics,
      surgical details, complications, disease-free survival (DFS), and overall
      survival (OS) were recorded prospectively. RESULTS: The majority (82%) of
      patients, median age 49 years (range, 18-77 y), had complete macroscopic
      cytoreduction (completeness of cytoreduction score, 0) despite a generally
      extensive tumor burden. Perioperative mortality and grade III/IV morbidity rates
      were 4% and 39%, respectively. Preliminary median DFS and OS have not been
      defined for appendix tumors at a median follow-up period of 16 months (range, 1
      86 mo). Median DFS and OS for colonic tumors are 8 months and 26 months,
      respectively, with a median follow-up period of 12 months (range, 1-48 mo).
      CONCLUSIONS: Combined regional treatment is feasible and holds significant
      promise for the treatment of peritoneal carcinomatosis.

PMID- 19393353
TI  - Anal fistula plug and fibrin glue versus conventional treatment in repair of
      complex anal fistulas.
AB  - INTRODUCTION: High transsphincteric fistulas are difficult to treat because
      fistulotomy of involved sphincter muscle results in incontinence. We compare our
      outcomes for anal fistula plug, fibrin glue, advancement flap closure, and seton
      drain insertion. METHODS: This is a retrospective study of patients treated for
      high transsphincteric anal fistulas. The primary outcome was full healing at 12
      weeks postoperatively. RESULTS: Between 1997 and 2008, 232 patients with anal
      fistula were identified in the St. Paul's Hospital Anal Fistula Database.
      Postoperative healing rates at the 12-week follow-up for the fistula plug, fibrin
      glue, flap advancement, and seton drain groups were 59.3%, 39.1%, 60.4%, and
      32.6%, respectively (P < .0001). CONCLUSIONS: Closure of the primary fistula
      opening using a biological anal fistula plug and anal flap advancement result in
      similar fistula healing rates in patients with high transsphincteric fistulae.
      These 2 strategies are superior to seton placement and fibrin glue. Given the low
      morbidity and relative simplicity of the procedure, the anal fistula plug is a
      viable alternative treatment for patients with high transsphincteric anal
      fistulas.

PMID- 19393355
TI  - Natural course and outcome of cystic lesions in the pancreas.
AB  - BACKGROUND: The number of patients identified with cysts of the pancreas is
      increasing. The current study was undertaken to assess the natural course and
      malignant potential of pancreatic cysts. METHODS: From 1995 to 2008, radiology
      records were reviewed for the presence of cystic lesions of the pancreas (CLP)
      characteristics, patient demographics, and follow-up. RESULTS: Eighty-two
      patients met the study inclusion criteria, with a mean age at time of diagnosis
      of 64.4 +/- 16.7 years. Mean cyst size was 1.36 +/- 1.05 cm, with 75.6% of
      patients having a solitary cyst. Thirteen patients underwent surgery. Operative
      intervention was statistically related to symptomatic, loculated cysts with the
      presence of calcifications (all P <.05). Malignancy was statistically related to
      symptomatic (P <.05), loculated cysts (P <.01), and male gender (P <.05).
      CONCLUSIONS: Our data show that most pancreatic cysts found on radiographic
      imaging are asymptomatic, solitary, and small and can be followed safely
      radiographically.

PMID- 19393356
TI  - Disparities in the treatment of colon cancer in octogenarians.
AB  - BACKGROUND: Disparities in healthcare for the elderly are understudied, despite
      the increasing proportion of patients over 80 years of age. Advanced age is a
      principal risk factor for colorectal adenocarcinoma, but there are few data to
      guide treatment in the elderly patient population. METHODS: We performed a
      retrospective review of prospectively gathered data on 10,433 patients diagnosed
      with primary colon tumors between 1998 and 2004. We compared demographics, stage
      at diagnosis, and initial treatment between patients younger than 80 years and
      those age 80 years or older. RESULTS: Patients who were >or=80 years old made up
      30% of the database. Older patients were less likely to have colectomy for
      advanced or metastatic disease than younger patients. Patients who were >or=80
      years of age had fewer lymph nodes removed than younger patients (11 vs 10, P
      <.01). Older patients were significantly less likely to receive chemotherapy for
      every stage of colon cancer than younger patients. When older patients did get
      chemotherapy, it was more likely to be with a single agent. Multivariate analysis
      revealed that predictors of receiving chemotherapy for patients >or=80 years of
      age include living in an urban county, younger age, and worse stage at diagnosis.
      CONCLUSIONS: Older patients make up a large portion of the patients treated for
      colon cancer and are treated less aggressively. While some of the treatment
      difference may be explained by medical factors, demographic factors affect
      treatment decisions as well.

PMID- 19393357
TI  - Intraoperative evaluation of sentinel lymph nodes in invasive lobular carcinoma
      of the breast.
AB  - BACKGROUND: In breast cancer treatment, sentinel lymph node (SLN) evaluation is
      used to identify patients who may benefit from axillary lymph node dissection
      (ALND). Intraoperative evaluation (IE) of SLNs facilitates immediate ALND.
      Controversy exists regarding the accuracy of intraoperative SLN evaluation for
      patients with invasive lobular carcinoma (ILC) compared to invasive ductal
      carcinoma (IDC). METHODS: Using breast cancer registry data from January 2003 to
      March 2008, the intraoperative SLN evaluation of 66 ILC and 810 IDC patients was
      compared to the final SLN pathology result and to the performance of ALND.
      RESULTS: In ILC, the sensitivities of IE for isolated tumor cells (<or=.2 mm,
      N0[i+], n = 9), micrometastases (>.2 mm and <or= 2.0 mm, N1mi, n = 6), and
      macrometastases (>2.0 mm, N1a-3a, n = 21) were 0%, 17%, and 71%, respectively.
      The specificity was 100%. IE identified 16/27 (59%) of SLN-positive (N1mi, N1a
      3a) axillae, resulting in synchronous ALND. Delayed ALND for false negative IEs
      (11/27, 41%) occurred in 7/11 patients (64%). In IDC, the sensitivities of IE for
      N0(i+) (n = 60), N1mi (n = 75), and N1a-3a (n = 129) metastases were 0%, 7%, and
      71%, respectively. The specificity was 99.6%. IE identified 97/204 (48%) of SLN
      positive (N1mi, N1a-3a) axillae, resulting in synchronous ALND. Delayed ALND for
      false negative IEs (107/204, 52%) occurred in 38/107 patients (36%). CONCLUSIONS:
      Sensitivity and specificity of intraoperative SLN evaluation is very similar in
      ILC and IDC patients. Intraoperative SLN evaluation facilitated synchronous ALND
      in concordance with recommended practice guidelines.

PMID- 19393358
TI  - Intact parathyroid hormone measurement 1 hour after thyroid surgery identifies
      individuals at high risk for the development of symptomatic hypocalcemia.
AB  - BACKGROUND: There is currently no consensus regarding the utilization of intact
      parathyroid hormone (iPTH) for predicting postthyroid surgery hypocalcemia. The
      objective of this study was to determine a threshold value for the 1-hour
      postoperative iPTH level that can identify those patients at significantly
      increased risk for the development of symptomatic hypocalcemia. METHODS: A
      prospective study of 21 individuals undergoing either total or completion thyroid
      operations was performed. One-hour postoperative iPTH levels were drawn along
      with ionized calcium at 6 hours postoperatively and at 7 am the following
      morning. Symptoms of hypocalcemia were recorded. RESULTS: Of the 21 patients
      recruited into the study cohort, there were 18 individuals that developed
      hypocalcemia (4 symptomatic and 14 asymptomatic) and 3 that remained
      normocalcemic. The mean iPTH level 1 hour postoperatively was significantly
      different when comparing the normocalcemic, asymptomatic hypocalcemic, and
      symptomatic hypocalcemic patient groups (6.50 pmol/L versus 3.76 pmol/L versus
      0.7 pmol/L, respectively; P = .007). An iPTH level <or=2.5 pmol/L was 100%
      sensitive for predicting which individuals would go on to develop symptomatic
      hypocalcemia. CONCLUSIONS: This study suggests that a 1-hour postoperative iPTH
      level <or=2.5 pmol/L can identify those individuals at risk for developing
      symptomatic hypocalcemia. Therefore, we recommend early calcium supplementation
      for these patients to decrease their postoperative morbidity from symptomatic
      hypocalcemia.

PMID- 19393359
TI  - An algorithm for the integration of breast magnetic resonance imaging into
      clinical practice.

PMID- 19393360
TI  - Fast electrochemical detection of anti-HIV antibodies: coupling allosteric
      enzymes and disk microelectrode arrays.
AB  - Here a novel electrochemical method for the rapid detection of anti-HIV
      antibodies in serum is presented. The novelty lies in the combination of
      allosteric enzymes and coulometry to yield a fast, simple and reliable HIV
      diagnostic method. We have used a previously developed beta-galactosidase enzyme
      that is efficiently activated by anti-HIV antibodies directed against a major B
      cell epitope of the gp41 glycoprotein. When these antibodies bind the enzyme, the
      3D conformation changes positively affecting the performance of the active site
      and, consequently, the enzyme activity is stimulated. Using 4-aminophenyl beta-D
      galactopyranoside (PAPG) as substrate yields p-aminophenol (PAP), which is
      reversibly oxidised at a very mild potential, ca. 0.37 V vs. Ag/AgCl over a range
      of electrode materials within the working pH range of beta-galactosidase. In the
      present case, photolithographically produced microelectrode arrays resulted in a
      detection limit of 4 microM for 4-aminophenol (PAP). The presence of anti-HIV
      antibodies results in enzyme activity increases above 50% which, combined with
      the sensitivity and response time afforded by the microelectrode arrays, allowed
      for the diagnosis of HIV in sera samples within an hour.

PMID- 19393361
TI  - Review: micro- and nanosized molecularly imprinted polymers for high-throughput
      analytical applications.
AB  - This review covers the analytical properties and applications of micro- and
      nanostructured molecularly imprinted polymers. The first two parts focused on
      their intrinsic and receptor properties specific to 0-1 dimensional MIP
      nanoobjects. The third part reviews the recent publication regarding the 2-3D
      patterned MIP structures mainly focusing on their sensor and microarray
      applications. Several patterning techniques that can be used for the fabrication
      of MIP microsensors/arrays are explained. Finally, a recent publication on some
      other nanomaterials (metal and semiconductor nanoparticles), which are compatible
      with MIP receptors to enhance the sensitivity, is discussed.

PMID- 19393362
TI  - Comprehensive liquid chromatography: fundamental aspects and practical
      considerations--a review.
AB  - In the quest for separation techniques capable of generating high peak
      capacities, comprehensive two-dimensional (2D) liquid chromatography (LC x LC) is
      a performant analytical tool for the analyses of complex mixtures. Interest in LC
      x LC has increased substantially over the past few years. The most significant
      and profitable difference between LC x LC and other multidimensional (MD) LC
      approaches is the subjection of every part of the sample to two individual
      separation dimensions. This results in a tremendous increase in resolving power,
      since the peak capacity of the comprehensive system approaches the product of the
      peak capacities of the first and second dimension separations when highly
      orthogonal separation mechanisms are combined. The present review discusses the
      theoretical aspects of LC x LC together with practical considerations for LC x LC
      method development. An extensive overview of different interface designs
      discussing their pros and cons is presented.

PMID- 19393363
TI  - Methylmercury determination in marine sediment and organisms by Direct Mercury
      Analyser.
AB  - An analytical method for simple and rapid determination of methylmercury in
      sediment and organism samples is described. The proposed method employs the
      oxygen combustion-gold amalgamation using Direct Mercury Analyser (DMA-80) after
      complete removal of MeHg by organic extraction and back extraction to an aqueous
      medium. DMA-80 instrument is equally suitable for the analysis of solid and
      liquid materials and has a good detection limit. The analytical performance of
      this method was evaluated by analysis of certified reference materials (CRM-580,
      IAEA-405, DORM-2, DOLT-3, SRM-2976 and SRM-2977) assessing its quality in terms
      of accuracy, repeatability and quantification limit. Furthermore total mercury
      and methylmercury have been analysed in sediment and organism samples collected
      during the XXI Italian Antarctic Expedition in Terra Nova Bay (Ross Sea, Northern
      Victoria Land). The results obtained show the validity of the proposed method as
      ready-to-use analytical method to analyse real samples.

PMID- 19393364
TI  - Effect of initial estimates and constraints selection in multivariate curve
      resolution--alternating least squares. Application to low-resolution NMR data.
AB  - A comprehensive study of the applicability of multivariate curve resolution (MCR)
      methods to series of T2-relaxation filtered 1H NMR spectra of a cross-linked
      polymer network is presented. A collection of Hahn-echo NMR spectra is obtained
      at different echo times, yielding two-way data. In this study the applicability
      of two different types of orthogonal-projection approach (OPA1 and OPA2) (column
      wise and row-wise) were tested. Four different strategies of alternating least
      squares methods were also examined (ALS1, ALS2, ALS3 and ALS4). These strategies
      differed on the order of measurement for which the constraints were applied in
      the final output, and the way in which SSR was calculated to monitor for
      convergence. In the spectral order of measurement, a non-negativity constraint
      was imposed, whereas in the time order of measurement, the signal was forced to
      follow an exponential decay. This yielded up to eight MCR configurations, giving
      different results. For solid-state NMR, the dissimilarity in NMR profiles is
      significantly lower than the dissimilarity in signal decays, and therefore OPA2
      performed better. A final output with a constrained solution in relaxation time
      was preferred (instead of a constrained solution in NMR spectra) for practical
      purposes. Differences between the solutions given from the two ALS configurations
      can be interpreted as a sign of lack of fit.

PMID- 19393365
TI  - Determination of the composition of counterfeit Heptodin tablets by near infrared
      chemical imaging and classical least squares estimation.
AB  - According to the WHO definition for counterfeit medicines, several categories can
      be established, e.g., medicines containing the correct active pharmaceutical
      ingredient (API) but different excipients, medicines containing low levels of
      API, no API or even a substitute API. Obviously, these different scenarios will
      have different detrimental effects on a patient's health. Establishing the degree
      of risk to the patient through determination of the composition of counterfeit
      medicines found in the market place is thus of paramount importance. In this
      work, classical least squares was used for predicting the composition of
      counterfeit Heptodin tablets found in a market survey. Near infrared chemical
      imaging (NIR-CI) was used as a non-destructive measurement technique. No prior
      knowledge about the origin and composition of the tablets was available. Good API
      (i.e., lamivudine) predictions were obtained, especially for tablets containing a
      high API (close to the authentic) dose. Concentration maps of each pure material,
      i.e., the API (lamivudine) and the excipients microcrystalline cellulose, sodium
      starch glycollate, rice starch and talc, were estimated. Below 1% of the energy
      was not explained by the model (residuals percentage) for every pixel in all 12
      counterfeit tablets. The similarities among tablets with respect to the total API
      percentage determined, as well as the corresponding concentration maps, support
      the classification of the tablets into the different groups obtained in previous
      work.

PMID- 19393366
TI  - A comparative study on several algorithms for denoising of thin layer
      densitograms.
AB  - This paper compares classical filtering techniques (Savitzky-Golay, Adaptive
      Degree Polynomial Filter, Fourier denoising, Butterworth and Chebyshev IIR
      filters) and the wavelet shrinkage (31 mother wavelets, 3 thresholding techniques
      and 11 decomposition levels). These techniques were compared with the original
      noisy signal and the reference signal, denoised experimentally by the averaging
      of 64 measurements. The best similarity to reference signal was observed in the
      case of filters, but they slightly oversmoothed the signal. The wavelet shrinkage
      gave less denoised signals. The significant influence of the thresholding
      technique and decomposition level was observed (the best conditions--the level 2
      or 3 and soft thresholding). Changing of the mother wavelet almost does not
      change the result, which is similar to the earlier literature findings. The
      presented results can be used as general recommendations for denoising of the
      densitometric fingerprints before applying further chemometric algorithms. The
      best choices are: Savitzky-Golay filter of appropriate (optimized against the
      autocorrelation) window width or wavelet shrinkage with Haar wavelet, soft
      thresholding and high decomposition level.

PMID- 19393367
TI  - Direct toxicity assessment of toxic chemicals with electrochemical method.
AB  - Electrochemical measurement of respiratory chain activity is a rapid and reliable
      screening for the toxicity on microorganisms. Here, we investigated in-vitro
      effects of toxin on Escherichia coli (E. coli) that was taken as a model
      microorganism incubated with ferricyanide. The current signal of ferrocyanide
      effectively amplified by ultramicroelectrode array (UMEA), which was proven to be
      directly related to the toxicity. Accordingly, a direct toxicity assessment (DTA)
      based on chronoamperometry was proposed to detect the effect of toxic chemicals
      on microorganisms. The electrochemical responses to 3,5-dichlorophenol (DCP)
      under the incubation times revealed that the toxicity reached a stable level at
      60 min, and its 50% inhibiting concentration (IC50) was estimated to be 8.0 mg L(
      1). At 60 min incubation, the IC50 values for KCN and As2O3 in water samples were
      4.9 mg L(-1) and 18.3 mg L(-1), respectively. But the heavy metal ions, such as
      Cu2+, Pb2+ and Ni2+, showed no obvious toxicity on E. coli. With the exception of
      Hg2+, it showed 40.0 mg L(-1) IC50 value when E. coli was exposed to its solution
      for 60 min. The lower sensitivity of DTA for the heavy metal ions could be
      attributed to the toxicological endpoint and the experimental conditions used.
      All results suggest that the DTA is a sensitive, rapid and inexpensive
      alternative to on-site water and wastewater toxic analysis.

PMID- 19393368
TI  - Development and application of an SPME/GC method for the determination of trace
      phthalates in beer using a calix[6]arene fiber.
AB  - A simple, low-cost and sensitive method for the determination of phthalate acid
      esters (PAEs) in beer has been developed based on solid-phase microextraction
      (SPME) followed by gas chromatography using a novel sol-gel calixarene-contained
      fiber. Generally speaking, matrix interference is one of the most important
      problems that researchers have to face when quantifying trace compounds in the
      complicated beer samples. In order to reproduce the influence of the matrix,
      synthetic beer solutions were popularly used, while they could not represent the
      real beer matrix absolutely. Owing to the good selectivity and high sensitivity
      of this new calixarene fiber, matrix interference from the beer samples was
      effectively avoided and low limits of detection (LODs) could be achieved. As a
      result, the SPME was performed in real beer matrices. Five experimental
      parameters including extraction temperature, extraction time, stirring speed,
      salt concentration and ultrasonic time were evaluated and optimized by means of a
      Taguchi's L25 (5(6)) orthogonal array experimental design. Under the optimized
      conditions, LODs of 0.003-3.429 microg L(-1) were obtained and the relative
      standard deviation values were < or =13.51% for all of the eight PAEs. The method
      was validated using standard addition methodology and recovery values were
      between 86.3% and 109.3%. The survey of three bottled beer samples showed that
      dibutyl-phthalate ester and bis(2-ethylhexyl)-phthalate ester (DEHP) were the
      main PAEs found in beer. The concentration of DEHP was as high as 5.24 microg L(
      1). In order to investigate the source of phthalates contamination in beer, the
      composition of phthalates in the plasticized polyvinyl chloride (PVC) gaskets of
      the lids was analyzed. Results revealed that the high content of DEHP
      incorporated in PVC gaskets could be a potential source of PAEs in bottled beers
      during transportation and storage.

PMID- 19393369
TI  - Preparation of polydimethylsiloxane/beta-cyclodextrin/divinylbenzene coated
      "dumbbell-shaped" stir bar and its application to the analysis of polycyclic
      aromatic hydrocarbons and polycyclic aromatic sulfur heterocycles compounds in
      lake water and soil by high performance liquid chromatography.
AB  - A "dumbbell-shaped" stir bar was proposed to prevent the friction loss of coating
      during the stirring process, and thus prolonged the lifetime of stir bars. The
      effects of the coating components, including polydimethylsiloxane (PDMS), beta
      cyclodextrin (beta-CD) and divinylbenzene (DVB) were investigated according to an
      orthogonal experimental design, using three polycyclic aromatic hydrocarbons
      (PAHs) and four polycyclic aromatic sulfur heterocycles (PASHs) as model
      analytes. Four kinds of stir bars coated with PDMS, PDMS/beta-CD, PDMS/DVB and
      PDMS/beta-CD/DVB were prepared and their extraction efficiencies for the target
      compounds were compared. It was demonstrated that PDMS/beta-CD/DVB-coated stir
      bar showed the best affinity to the studied compounds. The preparation
      reproducibility of PDMS/beta-CD/DVB-coated stir bar ranged from 3.2% to 15.2% (n
      = 6) in one batch, and 5.2% to 13.4% (n = 6) among batches. The "dumbbell-shaped"
      stir bar could be used for about 40 times, which were 10 extractions more than a
      normal stir bar. The prepared PDMS/beta-CD/DVB-coated "dumbbell-shaped" stir bar
      was used for stir bar sorptive extraction (SBSE) of PAHs and PASHs and the
      desorbed solution was introduced into HPLC-UV for subsequent analysis. The limits
      of detection of the proposed method for seven target analytes ranged from 0.007
      to 0.103 microg L(-1), the relative standard deviations were in the range of 6.3
      12.9% (n = 6, c = 40 microg L(-1)), and the enrichment factors were 19-86. The
      proposed method was successfully applied to the analysis of seven target analytes
      in lake water and soil samples.

PMID- 19393370
TI  - Determination of widely used non-steroidal anti-inflammatory drugs in water
      samples by in situ derivatization, continuous hollow fiber liquid-phase
      microextraction and gas chromatography-flame ionization detector.
AB  - The aim of this study was to develop an analytical procedure which allows the
      quantification of pharmaceuticals in water at the ng L(-1) level. Hence, it is
      reported research on the application of a rapid, inexpensive and simple
      continuous hollow fiber liquid-phase micro extraction (CHF-LPME) for the pre
      concentration and determination of non-steroidal anti-inflammatory drugs
      (NSAIDs), such as ibuprofen (IBP), naproxen (NAP), and ketoprofen (KEP), in
      wastewater. In this method, a 2.50 cm end sealed piece of a polypropylene hollow
      fiber was immersed into the organic solvent, octanol, for 30 s. After solvent
      impregnation with the pores of the fiber, the excess amounts of solvent were
      removed from inside the fiber, and 4.0 microL of octanol, as the acceptor phase,
      was injected into the fiber carefully. The fiber was settled using a microsyringe
      into a 10.0 mL glass test tube, and 20.00 mL of the aqueous solution (the donor
      phase), was circulated by a pump around it. After analyte extraction for an
      optimized period of time (20 min), 2 microL of the organic solvent was withdrawn
      into the microsyringe and injected into the GC-FID for further analysis. Finally,
      based on the optimized analytical conditions, the method was linear in the range
      of 2.5-500 ng L(-1). The limits of detection were 1-2 ng L(-1). Repeatability of
      this method on an intra-day scale was 3.4-10.2% (RSD%). NSAIDs have been detected
      in several municipal wastewater samples, and the concentration range was 9.0-19.0
      ng L(-1).

PMID- 19393371
TI  - Evaluation of principal cannabinoids in airborne particulates.
AB  - The determination of delta(9)-tetrahydrocannabinol (Delta9-THC), cannabidiol
      (CND) and cannabinol (CNB), primary active components in cannabis preparation,
      was carried out on airborne particulates by applying a specific procedure
      consisting of soot extraction by ultrasonic bath, purification by solvent
      partitioning, derivatization with N-(t-butyldimethylsilyl)-N-methyl
      trifluoroacetamide, and separation/detection through gas chromatography coupled
      with tandem mass spectrometry. The optimized procedure was found suitable for
      measuring the three psychotropic substances at concentrations ranging from ca.
      0.001 to ca. 5.0 ng cm(-3) of air, with recoveries always higher than 82%,
      accuracy >7.3% and precision >90%. Application of the procedure performed on
      field in Rome and Bari, Italy, demonstrated that all three compounds contaminate
      the air in Italian cities whereas in Algiers, Algeria, only cannabinol, the most
      stable in the atmosphere, exceeded the limit of quantification of the method. The
      relative percentages of the three cannabinoids in general reproduced those
      typical of the Cannabis sativa plant and were very different from those found in
      human blood, urine and sweat.

PMID- 19393372
TI  - Development of a LC-MS/MS method to monitor palmitoyl peptides content in anti
      wrinkle cosmetics.
AB  - Palmitoyl peptides are anti-aging agents widely used in cosmetics. This article
      describes the development of a LC-MS/MS analytical procedure that allows, after a
      liquid-liquid extraction procedure, their unambiguous detection in cosmetic
      formulation. MS/MS detection is shown to be specific regarding placebo
      formulations. Limits of quantification, linearity, accuracy and precision of the
      method were estimated. The results presented show that palmitoyl peptides can be
      thus reliably assayed. The palmitoylated pentapeptide palmitoyl-lysyl-threonyl
      threonyl-lysyl-serine (pal-KTTKS) was assayed in anti-wrinkle creams using
      palmitoyl-glycyl-histidyl-lysine (pal-GHK) as internal standard. From the results
      obtained, the influence of the formulation on pal-KTTKS availability is
      evidenced.

PMID- 19393373
TI  - Alternative GC-MS approaches in the analysis of substituted pyrazines and other
      volatile aromatic compounds formed during Maillard reaction in potato chips.
AB  - Several methods have been developed for the analysis of substituted pyrazines and
      related substances in potato chips. Following separation/detection approaches
      (all employing head-space solid phase microextraction, HS-SPME, for volatiles
      sampling), have been critically assessed in our study: (i) gas chromatography-ion
      trap mass spectrometry (GC-ITMS), (ii) gas chromatography-time-of-flight mass
      spectrometry (GC-TOFMS); (iii) comprehensive two-dimensional gas chromatography
      time-of-flight mass spectrometry (GC x GC-TOFMS). Although in none of the tested
      systems full chromatographic resolution of some isomeric pairs could be achieved,
      the use of GC x GC-TOFMS offered the best solution, mainly because of distinctly
      lower limits of quantification (LOQs) for all of 13 target alkylpyrazines. In
      addition to good performance characteristics, a non-target screening and
      tentative identification of altogether 46 N-containing heterocyclic compounds
      (pyrazines, pyrrols, pyridines, pyrrolidinones, and tetrahydropyridines) was also
      enabled.

PMID- 19393374
TI  - Sensitive determination of triazines in underground waters using stir bar
      sorptive extraction directly coupled to automated thermal desorption and gas
      chromatography-mass spectrometry.
AB  - An automated thermal desorption-gas chromatography-mass spectrometry method for
      the determination of triazin herbicides in aqueous solution with excellent
      sensitivity was developed. The method is based on the use of stir bar sorptive
      extraction. The main parameters such as extraction time, sample volume, the
      addition of salt and organic modifiers, desorption temperature, desorption flow
      and desorption time which affect the efficiency of the proposed methodology are
      fully discussed. The proposed method is sensitive and shows a good linearity
      within a range of 10-10000 ng L(-1) with correlation coefficients higher than
      0.998. Quantitation limits are, in all cases, below the limits accepted by
      European legislation for human waters consumption and ranging between 11.3 ng L(
      1) and 0.7 ng L(-1). The repetitivity, expressed as a relative standard
      deviation, has values of lower than 8% for all analytes. Using this method,
      determination of 10 triazines in underground water samples was successfully
      performed. The average concentrations obtained in the analysis of the spiked
      samples at two different levels of concentration correspond to mean recoveries
      ranging from 94.4+/-5.1% to 106.0+/-6.3% for a significance level of 0.05.

PMID- 19393375
TI  - A combination of ultrasonic assisted extraction with LC-MS/MS for the
      determination of organophosphorus pesticides in sludge.
AB  - A method has been developed for the analysis of a wide polarity range of the
      currently used organophosphorus pesticides (OPs) and their metabolites in sewage
      sludge samples. Extraction was carried out using ultrasonic assisted extraction
      (UAE) with different solvents. The levels of OPs in sludge were determined by
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) using electrospray
      ionization (ESI) in positive or negative ion mode. Extraction with acetonitrile
      containing 1% acetic acid gave the best results with recoveries between 83.2% and
      106.4% and RSD < or = 8.7%. Evaluation of matrix effect showed high ion
      suppression for OPs of intermediate polarity, which decreased to approximately
      50% by matrix dilution to an equivalent of 0.5 g of sludge per millilitre;
      however, for polar OPs, the matrix effect was negligible at the same
      concentration. Therefore, matrix-matched standards were used for OPs
      quantification. The limits of quantification were in the range of 1-14 ng g(-1).
      This method was successfully applied to real sludge samples collected from Madrid
      Province and chlorpyrifos along with its metabolite TCPY were the OPs found in
      sludge at the highest levels, 113-344 ng g(-1) and 33-307 ng g(-1), respectively.

PMID- 19393376
TI  - Peroxynitrite and reactive nitrogen species: the contribution of ABB in two
      decades of research.

PMID- 19393377
TI  - Understanding peroxynitrite biochemistry and its potential for treating human
      diseases.

PMID- 19393378
TI  - [Structural and functional neuroanatomy of attention-deficit hyperactivity
      disorder (ADHD)].
AB  - INTRODUCTION: Attention-deficit hyperactivity disorder (ADHD) is a common and
      impairing neuropsychiatric disorder with preschool onset. ADHD occurs in
      approximately 3-9% of the childhood population. There is a much higher incidence
      rate in boys who are around three times more likely than girls to be diagnosed.
      Approximately 30-60% of individuals diagnosed with ADHD in youth have symptoms
      that persist into adulthood. LITERATURE FINDINGS: Three subtypes of the disorder
      have been proposed in the current clinical view of ADHD: inattentive, hyperactive
      impulsive and combined type. Numerous problems are associated with ADHD: poor
      academic performance, learning disorders, subtle cognitive deficits, conduct
      disorders, antisocial personality disorder, poor social relationships, and a
      higher incidence of anxiety and depression symptoms into adulthood. Researchers
      have emphasized poor behavioural inhibition as the central impairment of the
      disorder. From the neuropsychological viewpoint, impairment of the "hot"
      affective aspects of executive functions, like behavioural inhibition and
      attention and the more cognitive, "cool" aspects of executive functions like self
      regulation, working memory, planning, and cognitive flexibility, are often
      reported by studies on ADHD. The hot executive functions are associated with
      ventral and medial regions of the prefrontal cortex (including the anterior
      cingulated cortex) and named "hotbrain" and the cool executive functions are
      associated with the dorsolateral prefrontal cortex and are called "coolbrain".
      DISCUSSION: Convergent data from neuroimaging, neuropsychology, genetics and
      neurochemical studies consistently point to the involvement of the frontostriatal
      network as a likely contributor to the pathophysiology of ADHD. This network
      involves the lateral prefrontal cortex, the dorsal anterior cingulate cortex, the
      caudate nucleus and putamen. Moreover, a growing literature demonstrates
      abnormalities affecting other cortical regions and the cerebellum. The
      exploratory brain regions of interest in which abnormalities have been
      identified, but that were not predicted by cognitive models of ADHD, are the
      temporal lobe, parietal lobe, occipital lobe and lateral ventricles. Anatomical
      studies suggest widespread reductions in volume throughout the cerebrum and
      cerebellum, while functional imaging studies suggest that affected individuals
      activate more diffuse areas than controls during the performance of cognitive
      tasks. More precisely, reductions in volume have been observed in the total
      cerebral volume, the prefrontal cortex, the basal ganglia (striatum), the dorsal
      anterior cingulate cortex, the corpus callosum and the cerebellum. Furthermore,
      hypoactivation of the dorsal anterior cingulate cortex, the frontal cortex and
      the basal ganglia (striatum) have also been reported. The paradigms mostly used
      in functional magnetic resonance imaging (fMRI) are tasks of motor inhibition,
      interference and attention such as the go/no-go, "stop-signal" and the Stroop.
      CONCLUSION: This review provides an overview of the main imaging studies that
      investigated the neurobiological substrate of ADHD. Some guidelines for future
      functional magnetic imaging studies are also suggested.

PMID- 19393379
TI  - [Motivational orientation and depressive symptoms in the elderly].
AB  - This article is focused on motivation and depression in later life. For about 20
      years, research on the motivation of elders has underlined the importance of the
      cognitive evaluation of life contexts, notably in terms of self-determination.
      This cognitive evaluation determines the motivational orientation for daily
      activities (notably the levels of intrinsic and extrinsic motivation). The
      purpose of this research was specifically to study the relationships between the
      existence of four types of motivation (intrinsic, self-determined extrinsic,
      nonself-determined extrinsic and amotivation) and the consequences for adaptation
      and well-being. The study, therefore, focused on the possible links between
      motivation and geriatric-depression level and explored the nature of this link.
      Forty persons aged 60 or over (31 women: 80.48+/-9.24; nine men: 80.56+/-9.48)
      who live in nursing homes (20 elderly) or in their own homes (20 elderly) were
      enrolled. Elderly persons were assessed with specific and standardized tools: the
      Elderly Motivation Scale (EMS, in the French version: EMPA) and the Geriatric
      Depression Scale (GDS). For the statistical analyses of the results, correlations
      and Mann-Whitney test were used. We found that in elderly people, the
      motivational styles (the four types of motivation) can be reliably measured and
      are related to geriatric depression. First, significant positive links were
      noticed between intrinsic motivation and depression scores and between self
      determined extrinsic motivation and depression scores. Conversely, significant
      negative links were noticed between nonself-determined extrinsic motivation and
      depression scores and between amotivation and depression scores. The most self
      determined elders presented low-depression levels, whereas the more nonself
      determined elders showed high-depression levels. Moreover, motivational styles
      significantly differed in the two groups (depressive or not depressive). The most
      depressive elders showed significantly lower-intrinsic and self-determined
      motivation levels. Our results support the hypothesis that motivational styles
      are related to important aspects (adaptation, well-being and depression) of the
      life of elderly people. Self-determination theory appears of high interest in
      research on aging and especially on the determinants of well-being in the elders.

PMID- 19393380
TI  - [Mortality of psychiatric inpatients in France during World War II: a demographic
      study].
AB  - INTRODUCTION: In France, World War II lasted from 1939 to 1945. Under-nourishment
      was a national problem, and was more severe in mental hospitals. The mortality of
      psychiatric inpatients in France during World War II has long been a
      controversial issue in the country. LITERATURE FINDINGS: Some authors wrote of
      the "soft extermination" of 40 000 mental patients, although this has been proven
      false. The historical study published in 2007 by Isabelle von Bueltzingsloewen
      provides in-depth description and analysis of starvation due to food restrictions
      in French mental hospitals. Although the French official statistic services
      published detailed data, no demographic study has been published so far. Such
      studies have been conducted in Norway and in Finland. "The influence of a period
      of under-nourishment upon mortality in mental hospitals can rarely be seen with a
      clarity equal to that in this work. The strict rationing was the same for
      everybody, but, extra muros, there was private initiative and ingenuity to help
      in alleviating the distress. Naturally, patients in institution had no ability to
      act on their own. The immense increase during the period of war from 1941 to 1945
      appeared both as an increase in the exact death-risk and as an increase in the
      disproportion with normal mortality. The men reacted more strongly than women;
      which is readily comprehensible on physiological grounds, as the rations were
      virtually the same for all." Excess mortality continued after the war. Even
      though under-nourishment had ceased, death rates from tuberculosis remained high
      the following year. Both papers state that the poor hygiene and bad living
      conditions existing in mental hospitals before the war worsened the effects of
      food restrictions. DEMOGRAPHIC DATA: French data were published by the General
      Statistics of France (SGF) that became the National Institute of Statistics and
      Economic Studies (Insee) in 1946. A series of datasets were published each year
      according to sex, diagnosis and type of psychiatric institution. In 1943, the
      outdated diagnostic classification was replaced by a more modern one, with
      reference to ICD. The same year, the age groups also changed (instead of 35-44,
      it became 30-39). Publication of data by type of institution was discontinued in
      1943; from 1945 to 1948, the only available data concerned patients in hospital
      on 31st December, by age, sex and diagnosis. General population data were
      published by the National Institute of Demographic Studies (INED). The data
      referring to civilian population during the war are provided by the Human
      Mortality Database. This study covers number of people in hospital, mortality
      rates by sex, age, diagnosis and type of institution, and standardised mortality
      ratios. These refer to the civilian population which is more relevant since
      mental patients would not have been allowed to join the armed forces, even if
      they had not been in hospital. Finally, mortality trends in mental hospitals are
      compared with those in "hospices for old, disabled or incurable people", in order
      to ascertain whether all vulnerable populations in institutions suffered to the
      same extent. The results show that the number of inpatients in 1945 was about
      half the total recorded in 1940, due to fewer admissions and to a large increase
      in the number of deaths. However, the number of discharges increased in 1940,
      even though the number of admissions had begun to slow down: many patients were
      sent to places offering better food and hygiene. The number of deaths began to
      rise as from 1939. Mortality rates were high in 1940 and especially in 1941, when
      almost one man in three and more than one woman in five died. Global rates did
      not change in 1942. In December that year, a government order stated that mental
      patients should receive more food. Mortality rates went down in 1943 and 1944,
      but rates did not return to the prewar values until 1946. In 1939, mortality
      rates are high but only among patients of 70 years of age or more. In 1940, they
      were highest above 55; in 1941, rates between ages 15 and 54 were double those of
      the preceding year. Thus, even though excess mortality affected all ages, its
      strongest effects were felt from the older patients to the younger ones from 1939
      to 1941. Trends according to diagnosis are difficult to interpret because of the
      change of classification in 1943. The patients suffered greatest hardship in
      public hospitals, which had no budget of their own and were run by the
      departments and lowest in private hospitals contributing to the public service,
      most of which were congregational and received religious funding. In 1941,
      standardised mortality ratios were more than three times higher than they were
      before the war. CONCLUSION: Comparison with people living in hospices shows that
      during the war mortality rates were 50% higher in these institutions, while they
      almost tripled in mental hospitals. The number of people who died of starvation
      and infectious diseases in mental hospitals from 1939 to 1945 can be estimated at
      about 45,500. However, mental patients were made specially vulnerable by
      circumstances that existed before the war in mental hospitals, in terms of food,
      hygiene and staffing, as suggested by an official document quoted in the paper.

PMID- 19393381
TI  - [Prescribing patterns of antipsychotics in 13 French psychiatric hospitals].
AB  - INTRODUCTION: The commercial introduction of atypical antipsychotics, called
      second-generation antipsychotics (SGAs), a few years ago, has led to a world-wide
      reappraisal of the established treatment strategies for people with psychotic or
      bipolar disorders. They permitted improvements in the pharmacologic management of
      psychiatric diseases. As compared to conventional neuroleptics or first
      generation antipsychotics (FGAs), they promised better efficacy especially on
      negative symptoms and cognitive impairments of psychiatric diseases and, at the
      same time, better tolerance on neurological side effects. Now, they have shown
      other side effects and they have a higher acquisition cost than FGAs. OBJECTIVES
      AND METHODS: The aim of this paper is to describe and analyse the prescribing
      practices of antipsychotic drugs in French psychiatric hospitals for adult
      inpatients and to compare them with other surveys and guidelines. In June 2004,
      we conducted a one-day, cross-sectional, observational and naturalistic study in
      13 hospitals, members of the PIC network. RESULTS: Two thousand one hundred and
      ninety-two prescriptions with antipsychotic treatment were collected. One
      thousand one hundred and fifty-four prescriptions (52.6%) included a SGA, but the
      FGAs were the most prescribed (65.8%; n=2259), principally cyamemazine (24.7%).
      There was one antipsychotic in 50.7% of prescriptions, two antipsychotics in
      42.2%, but the second neuroleptic used was a sedative (82.6%), principally
      cyamemazine. Multiple antipsychotics were present in 1081 prescriptions (49.3%),
      with an average number of 1.57 antipsychotics. A mood stabiliser, an
      antidepressant, an anxiolytic and a hypnotic were coprescribed in respectively
      37, 30.5, 65.1 and 41.6%. There were 2.48 psychotropic drugs associated with the
      principal antipsychotic; in total, with correctors of side-effects of the
      antipsychotics, there were 3.38 drugs per prescription. The SGAs aimed more often
      for psychotic (F20-F29) patients (61.9% versus 43.3% with FGAs), who were males
      (61.4% versus 68%), younger (42.6 years versus 44.1 years; p<0.02), with higher
      average daily doses, more associated with other neuroleptics (p<0.0004) and less
      associated with anticholinergic antiparkinsonian agents (p<10(-4)) than FGAs.
      Compared to other surveys, these results showed that the SGAs have become the
      first-line treatment for psychiatric disorders. The highest average daily doses
      corresponded to treatments of psychotic patients and, hence, the values might
      largely exceed the authorized maximum doses. Furthermore, in more than half of
      the cases, an FGA, generally a sedative, was associated with an SGA that did not
      comply with the principle of monotherapy established by the national and
      international guidelines; that also annulled the expected benefit of the SGAs on
      the awakening, cognition and the neurological tolerability of the treatment. The
      coprescriptions of the other psychotropic drugs to neuroleptics also remained the
      rule in psychiatry, showing all the complexity of pharmacological psychiatric
      medications. Prescriptions also included treatments for side effects of
      antipsychotics; even on the prescriptions including the SGAs, there was the
      coprescription of anticholinergic antiparkinsonian drugs, the deleterious
      character of which one knows on cognition. This resulted in a difficulty of
      understanding the prescription for the patient, associated with reduced
      compliance and increased risks of pharmacological side effects. The heterogeneity
      of the situations of crisis in psychiatric hospitals could make the strict
      application of guidelines' recommendations difficult. Nevertheless, the
      educational interventions in psychopharmacology for patients and the training
      campaigns for psychiatrists and nurses are necessary to improve the therapeutic
      management of the patient and ensure him/her optimal quality of life. CONCLUSION:
      This kind of survey, far too rare, was very important because it showed the
      routine clinical settings in which these new drugs were really used. The results
      showed that SGAs appeared to take the place of the FGAs used in the treatment of
      psychoses, particularly schizophrenia, but also in the treatment of mood
      disorders and they reflected actual clinical practices. Other surveys must be
      conducted to see whether our study confirms the general trend concerning the use
      of these drugs and, therefore, to reassess these prescribing practices.

PMID- 19393382
TI  - [How to differentiate schizophrenia from bipolar disorder using cognitive
      assessment?].
AB  - BACKGROUND: Historical aspects of the dichotomy between manic-depressive
      disorders and schizophrenia raise the question of a continuum between the two
      entities. Griesinger (1817-1868) proposed a unitary concept of psychosis:
      "Einheitspsychose", adaptations of which have survived until the present day.
      Although Kraepelin's traditional dichotomy is still a common base for clinicians
      every day: diagnosis, prognosis and treatment of psychotic disorders, recent
      epidemiological and neurobiological data are congruent with a dimensional aspect
      of psychosis. Epidemiological data are consistent with the existence of an
      individual and a familial overlap between bipolar disorder and schizophrenia.
      Schizophrenia is probably the most debilitating psychological disorder. It was
      primarily considered as a behavioural disorder, characterized by socially
      inappropriate and bizarre behaviour, but much attention has been focussed
      nowadays on the cognitive component and the cognitive pathology underlying
      schizophrenia. On the other hand, bipolar, or manic depressive disorder has been
      primarily considered as a mood or affective disorder, characterized by excessive
      swings of emotion and motivation. Manic depression is more about recurrent
      dimensions. However, symptoms associated with the diagnosis of schizophrenia can
      be associated with psychotic mood disorders: hallucinations and delusions (50%),
      disorganised speech and behaviour (all patients with moderate to severe mania or
      mixed episode), negative symptoms (all patients with moderate to severe
      depression). The social and job dysfunction may be due to disturbances in the
      volitional system in patients with schizophrenia or severe bipolar disorder.
      LITERATURES FINDINGS: A considerable body of literature exists concerning the
      relationship between cognitive impairment in schizophrenia, but there is less
      data about cognition in bipolar disorder. However, there are some notable
      similarities between data observed in schizophrenia and bipolar disorder. Many
      domains of cognition are disrupted in schizophrenia with varying degrees of
      deficit. Concerning mood disorders, cognitive dysfunction could be considered as
      a state marker. Globally some studies indicate that, compared with schizophrenia,
      those with bipolar disorder display a similar but less severe neuropsychological
      pattern of impairment. However, it is only recently that cognitive dysfunction
      has been recognized as a primary and enduring core deficit in schizophrenia and
      further studies in bipolar disorder are needed. DISCUSSION: In this way, it has
      been suggested that psychotic symptoms may be distributed along a continuum that
      extends from schizophrenia to psychotic mood disorders with increasing level of
      severity. An explicative theory has to explain the evolution and the similarities
      between those affections including genetic and environmental liability. Some
      individuals, who are at high risk for psychosis, can even develop bipolar
      disorder or schizophrenia. Likewise, common factors can explain cognitive and
      social disorders in psychosis. So, there are various arguments for the
      dimensional approach of psychosis. These data are not completely in contradiction
      with Kraepelin: schizophrenia is a chronic affection and bipolar disorder is a
      cyclic pathology. However, common symptoms are not in favour of a strict
      categorization.

PMID- 19393383
TI  - [Psychosocial distress and communication about cancer in ill partners and their
      spouses].
AB  - INTRODUCTION: Each cancer can have a psychological impact not only on the patient
      himself/herself, but also on his/her spouse. OBJECTIVE: Our study concerned 30
      couples encompassing a member treated for a cancer, non related to gender. It was
      aimed at determining the links between the levels of psychosocial distress
      measured in both members of each couple, patients' sociodemographic and clinical
      characteristics, as well as communication skills about cancer in both members of
      the couples. METHODS: Psychosocial distress and communication about cancer were
      measured by the general health questionnaire (GHQ-28) and the openness to discuss
      cancer in the nuclear family (ODCF), with an additional version adapted for the
      spouse on the occasion of this study. RESULTS: A positive correlation was found
      between the respective scores of the two members of the couples, for the GHQ-28
      (r=0.53; p=0.005) as well as for the ODCF (r=0.44; p=0.024). GHQ-28 scores were
      not associated with the sociodemographic characteristics of the patients, nor
      with the stage of cancer, the number of months elapsed since the diagnosis of
      cancer, or the ODCF personal or spouse's score. On the other hand, when the
      communication within each couple was classified into concordant (insufficient or,
      on the contrary, open for both members) or discordant (insufficient for one of
      the two members and open for the other), and after controlling for gender, higher
      levels of psychosocial distress were found in patients (p=0.038) as well in
      spouses (p=0.052) belonging to discordant compared with concordant couples.
      CONCLUSION: These results suggest an effect of contamination or a mutual
      reinforcement of the distress of each member of such couples, as well as the
      presence of relatively similar styles of communication in the two partners of
      each couple. They also underline the possible adaptive function of a restricted
      style of communication about cancer, if such a restriction is shared by both the
      members of the couple, and incites particular attention to be paid to couples
      where one of the partners, but not the other, adopt an open style of
      communication about cancer.

PMID- 19393384
TI  - [Severe forms of depression: the efficacy of escitalopram].
AB  - Severe forms of depression are a major therapeutic concern for psychiatrists.
      According to Health Authority recommendations, they require the systematic
      initiation of treatment with active drugs, and they respond less well to placebos
      than the less severe forms. Escitalopram, which is the most active enanthiomer of
      the racemic compound (citalopram), is tolerated well at the doses indicated in
      the marketing authorisation (10 to 20mg per day) and it is particularly effective
      in the severe forms of depression. Several studies have compared escitalopram to
      another specific serotonin recapture inhibitor (SSRI) in severe depression. In a
      24-week study, 20mg per day of escitalopram, compared to 40mg per day paroxetin,
      demonstrated significantly greater efficacy (p<0.05) on the primary criterion
      (modification of the total MADRS score between inclusion and the end of the
      study). In this same study, the difference in favour of escitalopram increased in
      parallel with the increase in initial severity. In a grouped analysis of three
      studies versus citalopram, the superior efficacy of escitalopram also increased
      in parallel with the initial severity. The antidepressants, combined serotonin
      recapture inhibitors and noradrenalin (SRINA), might, in theory, be more
      effective than the SRI because of their broader mode of action. Recent data on
      escitalopram have invalidated this fact. In a study comparing 20mg per day of
      escitalopram to 225mg per day of venlafaxine during eight weeks in severely
      depressed patients (MADRS>30), escitalopram led to a significantly enhanced
      improvement (p<0.05). A grouped analysis of two similarly designed studies showed
      that the difference in favour of escitalopram increased at the same time as the
      initial severity increased. An analysis of two studies comparing 10 to 20mg per
      day of escitalopram to 60mg per day of duloxetine in severely depressed patients,
      revealed the superior efficacy of escitalopram in the sub-sample of severely
      depressed patients (p<0.01), with significant superiority on each of the 10 items
      of the MADRS taken singly. Despite the limits of regrouped analyses, all these
      results underline the fact that escitalopram is at least as effective as the
      comparators, and notably compared to the two SRINA studied, in the severe forms
      of depression.

PMID- 19393385
TI  - [Cognitive remediation and cognitive assistive technologies in schizophrenia].
AB  - BACKGROUND: Cognitive impairments are a core feature in schizophrenia. They
      impact several cognitive abilities but most importantly attention, memory and
      executive functions, consequently leading to great difficulties in everyday life.
      Most schizophrenia patients need assurance and require assistance and help from
      care workers, family members and friends. Family members taking care of a patient
      have additional daily work burden, and suffer psychological anguish and anxiety.
      Therefore, improving cognitive functions in schizophrenia patients is essential
      for the well-being of patients and their relatives. Reducing these deficits may
      decrease the economic burden to the health care system through lower numbers of
      hospital admissions and shorter hospitalisation periods, for example. Cognitive
      rehabilitation was developed to address the limited benefits of conventional
      treatments on cognitive deficits through the use of assistive technology as a
      means of enhancing memory and executive skills in schizophrenia patients.
      OBJECTIVE: To provide clinicians with comprehensive knowledge on cognitive
      trainings, programs of remediation, and cognitive assistive technologies. METHOD:
      Literature review. A search in the electronic databases (PubMed, EMBASE, Index
      Medicus) for recent articles in the last 10 years related to cognitive
      remediation published in any language using the words: cognitive and remediation
      or rehabilitation and schizophrenia, and a search for chapters in psychiatry and
      rehabilitation textbooks. RESULTS: We found 392 articles and 112 review paper
      mainly in English. First, we identified cognitive remediation programs that were
      beneficial to schizophrenia patients. Programs available in French (IPT, RECOS,
      and RehaCom) and others (CET, NET, CRT, NEAR, APT and CAT) were identified. In
      addition, since memory and executive function impairments could be present in
      people without schizophrenia, we reviewed inventories of cognitive assistive
      technologies proven to enhance cognitive skills in other populations. Finally, we
      present a review of recent studies testing innovative devices developed to assist
      schizophrenia patients. DISCUSSION: First, we found several cognitive programs
      proven to be effective with schizophrenia patients, but only three were validated
      in French. It could be useful to adapt other programs for French-speaking
      populations. Unfortunately, we found that very few of the existing cognitive
      assistive technologies are proposed to be used with schizophrenia patients. In
      fact, most of the available cognitive orthoses were tested primarily in people
      with neurological injuries (for example, various memory impairments caused by
      traumas), and in elderly illnesses (like Alzheimer disease). Devices for patients
      with mental deficits (e.g., mental retardation) were developed later, and only
      very recently explored for use in schizophrenia. As a result of an international
      collaboration between France and Canada, currently a tool called MOBUS is being
      tested. This technology aims at improving the autonomy of schizophrenia patients,
      by helping them plan and remember their daily activities. Furthermore, it
      encourages patient-caregiver communication, and permits monitoring patients'
      subjective reports of their symptoms. The use of cognitive assistive technologies
      is not meant to isolate patients by replacing the human element of relatives and
      caregivers by a machine. On the contrary, they offer a sense of security and they
      improve interpersonal relationships by permitting enhanced autonomy and greater
      self-confidence. Finally, a literature review of cognitive remediation in
      schizophrenia emphasizes the importance of a structured application of the
      technique in order for it to succeed. First, it is crucial to detect the
      impairments that will be targeted in each patient presenting a specific pattern
      of impairments. For this purpose, validated and customised neuropsychological
      tests are required. Then, cognitive remediation programs must be customised to
      each patient's needs in order to motivate the patient to participate. Finally,
      long-term effects must be assessed in order to verify whether reinforcement is
      needed. Following these steps, most of the studies show an improvement in the
      well-being of patients with schizophrenia. These recommendations are also
      suitable for the cognitive remediation programs, as for treatments with cognitive
      assistive devices. An important hurdle facing the advance of cognitive assistive
      technology programs is that different research groups work individually without a
      coordinated effort to improve and validate the existing programs. CONCLUSION:
      Schizophrenia treatments must take into account not only patients' symptoms, but
      also the associated cognitive deficits which constitute an important factor in
      their social problems. It has been shown that several cognitive remediation
      programs are efficient in schizophrenia. New technologies complement the benefits
      of such programs, and support pharmacological treatments and psychotherapies.

PMID- 19393386
TI  - [Treatment of a serious autistic disorder in a child with Naltrexone in an oral
      suspension form].
AB  - CLINICAL BACKGROUND: Autism is a developmental disorder that is usually diagnosed
      in early childhood. According to ICD-10 criteria, autism can be characterized by
      delays in language skills, by impaired social interaction, verbal or non-verbal
      communication and by repetitive, stereotyped or severely restricted activities
      and interests. The causes of autism are not yet elucidated, but both genetics and
      environment seem to play a role in 10 to 25% of autism cases. Several biochemical
      abnormalities, such as impairment of serotoninergic, catecholinergic,
      dopaminergic, and opioid systems have been reported. Autism therapies are
      designed to treat symptoms, and medication can be associated with
      psychoeducational and environmental interventions. Generally, the medications
      that are currently used are not intended for autism, and must be used with
      caution and selected according to the type and intensity of symptoms. The most
      common medication consists of psychotropic therapies by administration of
      dopaminergic and/or serotoninergic receptor antagonists (haloperidol,
      risperidone, clomipramine). Several drugs, such as anxiolytics (buspirone), mood
      stabilisers (lithium, sodium valproate), vitamins (vitamins B6, B12) or opioid
      antagonists (naltrexone) can be prescribed, in second intention, in cases of
      severe behavioural disorders. The prescription of opioid antagonists is based on
      the possible implication of an opioid system disorder observed in some cases.
      Nevertheless, several clinical studies reveal its variable effectiveness.
      Naltrexone is a competitive antagonist of opioid receptors OPRM1, OPRD1 and
      OPRK1. In France, this drug is prescribed for treating opioid and alcohol
      dependence. Moreover, several studies describe naltrexone as a possible treatment
      of autistic children in cases of developmental disorder and hyperactivity.
      CLINICAL CASE: In the Child and Adolescent Psychopathology Department of Sainte
      Anne's Hospital, autistic children benefit from a multidisciplinary treatment
      program that sometimes includes the administration of psychotropic medication.
      One of these children presented with a severe autistic disorder according to the
      Childhood Autism Rating Scale (CARS). Considering ICD-10 criteria, he benefited
      from a multidisciplinary program, associating cognitive psychotherapy,
      psychomotor rehabilitation, speech therapy and educational intervention. However,
      persistent sleep disorder and motor instability led to successive prescriptions
      of several different psychotropic drugs. Initial treatment by thioridazine (10mg
      per day) followed by propericiazine (2.5mg per day) improved sleep, but was not
      efficient in reducing self-mutilating behaviour. A new treatment by risperidone
      (from 0.5mg to 1.5mg per day) was therefore chosen; however it lost its efficacy
      after five months. Finally, an anxiolytic (cyamemazine) and a thymoregulator
      (sodium valproate) were successively tried without yielding any clinical
      improvement. Owing to the persistence of communication difficulties, major
      instability, self-mutilating behaviour and heteroaggressiveness, treatment with
      naltrexone was subsequently chosen with parental consent. In France, naltrexone
      hydrochloride is only available in tablet form (Nalorex 50mg and Revia 50mg),
      which is not adapted to children at the efficient dose. Consequently, an oral
      suspension form marketed in Spain (Antaxone 50mg) was imported, having obtained
      the Afssaps' (the French drug administration) authorisation for its temporary
      use. The Connors and Nisonger scales were used as outcome measures of behavioural
      symptom change. The Conners scale is used to assess attention deficit and
      hyperactivity, whereas the Nisonger scale analyses social skills and behaviour
      disorders in children and adolescents with mental retardation. The onset of
      treatment, at a dose of 1mg/kg/day, led to a transitory increase in negative
      behaviour. However, a dose of 0.75mg/kg per day subsequently led to significant
      improvements, as shown by outcome measurements. Self-mutilating behaviour
      disappeared completely. Certain side effects were observed, namely transitory
      sedation at the beginning of treatment and moderate constipation. CONCLUSION:
      This clinical case confirms that treatment of a serious autistic disorder in
      children using Naltrexone in oral suspension form is a potentially interesting
      therapeutic alternative for treating behavioural symptoms resistant to classical
      drug therapy.

PMID- 19393387
TI  - [Chlorpromazine-induced agranulocytosis: a case report].
AB  - CASE REPORT: We report the case of a 50-year-old man, treated with chlorpromazine
      for schizophrenia, who developed an agranulocytosis. Three mechanisms of drugs
      induced agranulocytosis have been reported: toxic, genetic and immune.
      Phenothiazines are responsible for drug-induced agranulocytosis. This patient had
      been treated with first and second generation antipsychotic drugs during his life
      and had already been exposed to chlorpromazine or other phenotiazines without any
      signs of toxicity. However, two months after the introduction of chlorpromazine
      he presented an agranulocytosis (leukocytes 1.4G/L and neutrophils 0.2G/L). After
      discontinuation of chlorpromazine, blood count returned to normal. The role of
      chlorpromazine in inducing toxic agranulocytosis was based on: (i) normal blood
      count before the introduction of chlorpromazine; (ii) occurrence of
      agranulocytosis within the first weeks of chlorpromazine treatment; (iii) normal
      bone marrow and blood count after discontinuation of chlorpromazine; (iv)
      chlorpromazine was the only new drug prescribed to this patient at the time the
      agranulocytosis occurred. Risk factors for toxic agranulocytosis in this patient
      were: old age, association of phenothiazine with other drugs known to be able to
      induce agranulocytosis, and past history of use of high doses of chlorpromazine.
      DISCUSSION: This case report highlights the risk of chlorpromazine in inducing
      agranulocytosis, a risk underestimated in regard of the clozapine risk to induce
      agranulocytosis or neutropenia. For this reason, it seems reasonable to recommend
      performing a blood count before introduction of phenothiazine in patients with
      risk factors for toxic drug-induced agranulocytosis (old age, female, receiving
      other drugs with a high potential to induce agranulocytosis and having received
      high doses of phenothiazine for a long time).

PMID- 19393388
TI  - [Clinical features of suicide occurring in schizophrenia (I). Risk-factors
      identification].
AB  - INTRODUCTION: Suicide is the leading cause of premature death in schizophrenia.
      Approximately 10 to 13% of deaths in schizophrenia are explained by suicide,
      despite widespread availability of generally effective antipsychotic treatments
      and suicide attempts have been reported among 20 to 50% of patients. This
      relatively low ratio of attempts/suicide is consistent with greater lethality of
      means - more violent - and intents - less ambivalence - in this population.
      LITERATURE FINDINGS: Many studies have focused on risk factors and clinical
      characteristics for completed and/or attempted suicide. Commonly,
      sociodemographic risk factors for suicide are male sex, younger age and, among
      women, being unmarried, divorced or widowed. Previous suicidal behaviour is a
      strong risk factor for suicide and contrary to the common view, schizophrenic
      patients often communicate their suicidal intents shortly before death. Moreover,
      family history of suicide is associated with a heightened risk of suicide and is
      independent of the diagnosis, according to the growing literature that shows that
      vulnerability to suicidal behaviour is independent of psychiatric diagnosis.
      Suicide can occur throughout the entire course of schizophrenia. This is
      particularly true in those high-risk periods: early phase of the disease, active
      illness phase, period of relapse or during a depressive episode. The role of
      insight and positive symptoms remains unclear and probably needs further studies.
      Although not specifically for people with schizophrenia, hopelessness is a major
      risk factor and tragic loss is often presented as a trigger for suicide. It has
      been suggested that treatment side-effects, such as akathisia are associated with
      suicidal behaviour. CONCLUSION: A better knowledge of risk and protective factors
      is necessary to prevent suicide and suicidality.

PMID- 19393389
TI  - [Assessing various aspects of the motivation to eat that can affect food intake
      and body weight control].
AB  - Over the last 30 years, several questionnaires have been developed and validated
      in order to assess many aspects of the motivation to eat that might be
      susceptible to impair adequate food intake and body weight control. A few of such
      questionnaires are described here, in particular, the "Three Factor Eating
      Questionnaire" also called the "Eating Inventory", and the "Dutch Eating Behavior
      Questionnaire". Critical aspects of the motivation to eat assessed by these tools
      are presented, such as dietary restraint, disinhibition, hunger, vulnerability to
      eat in response to external cues or emotional states, etc. These questionnaires
      were developed for use in the general population with the aim to identify
      critical aspects of the motivation to eat that might predispose to weight gain.
      They have been widely used in many countries and have allowed an improved
      understanding of the individual characteristics that predispose to body weight
      gain or resistance to weight loss. Originally, poor body weight control was
      attributed to a high level of dietary "restraint", or in other words, the
      tendency to deliberately restrict one's food intake for body weight control
      purposes. Such dietary restraint was suspected to lead to a number of physical
      and psychological difficulties, among which poor self-esteem and a paradoxical
      tendency to gain weight, resulting from the incapacity to maintain strict
      restraint over time. More recent studies have established that a motivational
      trait called "Disinhibition" is a strong predictor of body weight gain over time
      and of poor outcome of dieting. "Disinhibition" corresponds to a tendency to lose
      control over one's eating behavior and ingest excessively large quantities of
      food substances, in response to a variety of cues and circumstances. In addition
      to its untoward effect on weight, disinhibition also predicts various risk
      factors and pathologies, such as hypertension and diabetes. Other potentially
      critical dimensions for adequate body weight control are "emotional eating" and
      "externality", which represent an individual's vulnerability to eat in response
      to emotional states or external cues, respectively. These questionnaires have
      been translated into French and validated for the French population. Average data
      are available for normal weight and obese French men and women. A gender
      difference is often reported: women, and even young girls, tend to have higher
      scores than males for most dimensions. These questionnaires have been extensively
      used in populations without psychiatric disorders, with the only exception of
      diagnosed eating disorders such as anorexia and bulimia nervosa. The
      questionnaires have not been used until now in populations with other types of
      psychiatric disorders, such as schizophrenia or bipolar disease. Their relevance
      for such populations is now an important question, since last generation
      pharmaceutical treatments of such psychiatric disorders seem to adversely affect
      body weight control. It then becomes critical to know whether the psychological
      dimensions assessed by such questionnaires reflect the action of pharmacological
      agents that induce weight gain. A research project is now in progress at Sainte
      Anne Hospital to investigate many dimensions of the motivation to eat, as
      assessed by the questionnaires, in psychiatric patients receiving various types
      of antipsychotic agents. The results of this original study might provide hints
      about the mechanisms that lead to body weight gain in patients receiving certain
      types of antipsychotic pharmacological agents and potentially help in preventing
      or reversing the weight gain associated with such treatments.

PMID- 19393391
TI  - [Use of cocaine and neuropsychological damage. Clinical implications].
AB  - The use of cocaine is a worldwide problem, not only because of its high
      prevalence but also because of the serious medical and social repercussions. The
      brain is one of the organs more directly affected by the consumption of cocaine.
      It provokes vascular damage, but especially alterations at the level of receptors
      and neuromodulators, that have severe repercussion on cognitive functioning.
      These alterations play an essential role in the social conduct of the individual
      and in his daily functioning, as well as in the perpetuation of the addiction and
      prognosis. Moreover, they determine the therapeutic results and the model of
      psychological intervention on a definitive way. This work tries to summarize and
      update the existing evidences concerning the neuropsychological damage provoked
      by the consumption of cocaine, its functional impact and clinical implications,
      as well as the questioned reversibility with the continued abstinence.

PMID- 19393392
TI  - [A decade of recombinant human thyrotropin].

PMID- 19393393
TI  - [Safety of iodine supplementation during pregnancy in mild-to-moderate iodine
      deficient areas].

PMID- 19393398
TI  - Undertreatment of allergy: exploring the utility of sublingual immunotherapy.
AB  - Allergic syndromes are highly prevalent and are comprised of a wide variety of
      clinical problems, including rhinitis, conjunctivitis, atopic dermatitis and
      urticaria, asthma, and food allergies. Numerous studies have shown that allergic
      syndromes are both underdiagnosed and undertreated. This is related to many
      factors, including trivialization of allergic conditions by physicians and
      patients, failure to adhere to diagnostic and treatment guidelines, and
      dissatisfaction with conventional pharmacologic treatments. Immunotherapy
      involves the administration of allergen extracts in an attempt to induce
      immunologic tolerance and has been used for the treatment of allergic syndromes
      and the prevention of long-term complications. Conventional subcutaneous
      immunotherapy is effective but is also associated with a risk of serious adverse
      events, requires administration by a trained health care professional, and is
      contraindicated in certain populations. By contrast, sublingual immunotherapy has
      been used extensively in Europe and possesses most of the benefits of
      subcutaneous immunotherapy along with increased safety, tolerability, and
      convenience. This narrative review explores data from selected clinical studies
      and concludes that sublingual immunotherapy may be well suited to fill the gap
      posed by the undertreatment of allergic syndromes in the United States.

PMID- 19393399
TI  - Sublingual immunotherapy for inhalant allergy: cautious optimism.
AB  - Sublingual immunotherapy (SLIT) is being utilized with increasing frequency in
      both Europe and the United States. While the data with commercially-prepared
      single-antigen SLIT appear promising, there has been an extrapolation of these
      data beyond the scope of the well-controlled clinical trials that have been
      published in the literature. In this environment of enthusiasm, it is prudent to
      examine variables that are relevant in evaluating how SLIT can be incorporated
      into American allergy practice on a broader scale. This commentary will discuss
      five areas of potential concern in moving toward wider implementation of SLIT:
      (1) patient selection for treatment; (2) pattern of sensitization; (3) dosing,
      preparation, and delivery; (4) safety concerns; and (5) cost of therapy.
      Additional research is necessary to adequately address these important issues to
      ensure that SLIT will offer a safe, well-tolerated, and effective treatment for
      Americans with inhalant allergy.

PMID- 19393400
TI  - Penalties for health care fraud and abuse: January 2007-March 2008.
AB  - This commentary details the providers, penalties, and affected regions resulting
      from US health care fraud and abuse prosecutions from January 2007 to March 2008.
      Database review found that over $3 billion in fines as well as incarceration in
      some cases were ordered for 21 convicted providers, 68 percent of whom were
      physicians, and to 41 nonproviders, most of whom were vendors of durable medical
      goods (36%), individual citizens (18%) and health care corporations (17%). Fewer
      claims were found against pharmaceutical firms (7%) and medical equipment
      manufacturers (4%). Most verdicts were in the state of Florida. False claims
      accounted for most of the violations for both providers and nonproviders. These
      severe repercussions of malfeasance should promote careful consideration and
      construction of the terms of engagement between health care providers,
      corporations, and payers.

PMID- 19393401
TI  - Hearing aids and cochlear damage: the case against fitting the pure tone
      audiogram.
AB  - Herein we propose a different approach to hearing aids, an approach that flows
      logically from the pathophysiology of cochlear disorders. This approach
      challenges some central tenets of the industry by 1) suggesting that many, if not
      most, cases would be better served by flat, undistorted gain across all
      frequencies rather than by "fitting" gain to the audiogram; and 2) suggesting
      that most of the improvements in hearing aid technology are targeted at reducing
      patient complaints as opposed to increasing measurable word recognition
      performance. We recommend that it is better to accommodate the damaged cochlea in
      these cases than to attempt to reverse-engineer the audiometric test results.

PMID- 19393390
TI  - [Cardiovascular complications at 1-year of follow-up in patients with
      atherothrombosis. On behalf of Spain's REACH Registry].
AB  - BACKGROUND AND OBJECTIVE: The REACH Registry is the largest worldwide designed to
      obtain information on cardiovascular risk factor control and preventive treatment
      in a population who have, or are at risk of having, symptoms of atherothrombosis.
      The objective of this study is to show the results of cardiovascular events
      obtained in a sample of the Spanish population at one year follow-up and
      intervention. MATERIAL AND METHOD: The REACH Spain registry is a prospective
      cohort study of subjects with vascular risk factors (ORF) for atherothrombosis or
      with symptomatic vascular disease (VD): coronary artery disease (CAD) and/or
      cerebrovascular disease (CVD) and/or peripheral artery disease (PAD). The main
      outcome measures were rates of all-cause mortality, cardiovascular (CV) death,
      and the overall combined CV death, myocardial infarction (MI), or stroke and CV
      hospitalization at one year follow-up. RESULTS: In Spain 2,516 patients were
      recruited and 2,252 completed one year follow-up, the mean age was 68,1 (73,8%
      men), 11,6% of subjects with ORF and 88,5% with VD, 55% with CAD, 33% with CVD
      and 17% with PAD. The annual rate of all-cause mortality in VD and ORF groups
      were 3,57% and 1,98% (NS) respectively, while for CV death they were 2,69% and
      0,62% (P<.05) and for overall combined CV death myocardial infarction (MI), or
      stroke and CV hospitalization they were 15,34% and 5,47% (P=.0001). The annual
      rate of CV death for CAD, CVD and PAD groups were 3,47%, 2,78% and 1,46%
      respectively, and for the overall combined CV death, myocardial infarction (MI) ,
      or stroke and CV hospitalization they were 18,52%, 13,75% and 14,52%. These event
      rates increased with the number of symptomatic arterial disease locations from
      0,1,2 or 3 for CV death (0,62%, 2,46%, 3,55% and 4,32%, respectively P<.05) and
      for overall combined CV death myocardial infarction (MI), or stroke and CV
      hospitalization (5,50%, 4,18%, 20,59% y 19,40%, respectively P<.0001). At one
      year follow-up, 82,8% of the patients were with at least one antiplatelet drug
      and 86,2% were receiving lipid-lowering agents. CONCLUSIONS: The REACH Spain
      Registry at one year follow-up in patients with atherothrombotic disease or at
      risk of having symptoms of atherothrombosis shows a high rate of all-cause
      mortality and of overall combined major CV events, which is becoming higher as
      the number of symptomatic arterial disease locations increases.

PMID- 19393402
TI  - Symptom-specific outcomes of endoscopic sinus surgery: a systematic review.
AB  - BACKGROUND: Although multiple studies have demonstrated that symptoms of chronic
      rhinosinusitis (CRS) improve after endoscopic sinus surgery (ESS), a systematic
      large-scale evaluation of specific symptom response has not been performed.
      OBJECTIVE: To analyze the relative effectiveness of surgery in the improvement of
      individual CRS symptoms. STUDY DESIGN: A literature search of MEDLINE, EMBASE,
      Web of Science, Cochrane databases, and other Web-based sources from January 1,
      1980 through June 1, 2008 was performed. Studies of 20 or more adult patients
      with CRS that used symptom severity scores to analyze at least 3 major CRS
      criteria (facial pressure, nasal obstruction, postnasal discharge, and hyposmia)
      or 2 major CRS criteria plus headache were included. SUBJECTS AND METHODS:
      Inclusion criteria were met by 21 of 289 ESS studies reviewed. Meta-analysis was
      conducted for each symptom separately with the standardized difference between
      the preoperative and postoperative severity scores as the effect size (ES).
      RESULTS: A total of 2070 patients with CRS were studied a mean of 13.9 months
      after ESS. All symptoms demonstrated improvement compared with their respective
      preoperative severity scores by an overall ES of 1.19 (95% confidence interval,
      0.96 to 1.41; I(2) = 81.7%) using the random-effects model. Nasal obstruction
      (ES, 1.73) improved the most, with facial pain (ES, 1.13) and postnasal discharge
      (ES, 1.19) demonstrating moderate improvements. Hyposmia (ES, 0.97) and headache
      (ES, 0.98) improved the least. CONCLUSION: The relative improvements in major CRS
      symptoms and headache after surgery are similar, with the exception of nasal
      obstruction, which improves most.

PMID- 19393403
TI  - Z-palatopharyngoplasty for obstructive sleep apnea/hypopnea syndrome.
AB  - OBJECTIVE: To explore the feasibility, outcomes, and factors affecting the
      outcome of Z-palatopharyngoplasty (ZP3) in the treatment of severe obstructive
      sleep apnea/hypopnea syndrome (OSAHS). STUDY DESIGN: Case series with chart
      review. METHODS: ZP3 was performed on 34 Friedman stage II/III OSAHS patients
      with a posterior airway space (PAS) > or = 11 mm. Postoperative follow-up was at
      least 6 months, and the differences between responders and nonresponders were
      analyzed. RESULTS: On the basis of success criteria, defined as an apnea-hypopnea
      index < 20 and a decrease > 50 percent, the success rate was 64.7 percent. The
      lowest oxygen saturation (LSaO(2)), percentage of time with an oxyhemoglobin
      saturation below 90 percent (CT(90)), mandibular plane angle (MPA), mandibular
      body length, position of the tongue, and Friedman clinical stage differed
      significantly between responders and nonresponders. The logistic regression
      analysis showed that MPA and Friedman stage were the key predictors of ZP3
      surgical success. The best cutoff points for LSaO(2), CT(90), and MPA were 72
      percent, 22.80 percent, and 29.40 degrees , respectively. CONCLUSIONS: Factors
      affecting the outcome of ZP3 included LSaO(2), CT(90), MPA, mandibular body
      length, position of the tongue, and Friedman clinical stage. Of these, the MPA
      and Friedman clinical stage were most influential.

PMID- 19393405
TI  - Adjuvant use of liquid alginate suspension for post-tonsillectomy morbidity:
      double-blind randomized clinical trial of efficacy.
AB  - OBJECTIVE: To evaluate the efficacy of liquid alginate suspension in alleviating
      post-tonsillectomy morbidity in adult patients. METHODS: A prospective, double
      blind, randomized, placebo-controlled study comparing the effect of liquid
      alginate suspension with placebo was performed on 40 patients who underwent
      tonsillectomy at Derince State Hospital, Kocaeli, Turkey. The patients were
      randomly chosen, and each used liquid alginate suspension four times daily or a
      placebo solution at the same regimen. Tonsillectomy was performed under general
      anesthesia by cold dissection and suture ligation. Patients were examined at
      postoperative days 1, 3, 5, and 7 for healing, instructed to note the amount of
      analgesics used, and asked to mark the visual analog score of throat pain every
      day for a week. RESULTS: The study group had statistically significant lower pain
      scores at day 2 (P = 0.03). Study group required less analgesic than the control
      group during the study period, but the difference was statistically different
      only on day 2 (P = 0.003) day. Healing was statistically significant on day 5 (P
      = 0.03) in the study group. CONCLUSION: Use of the antireflux suspensions in
      patients undergoing tonsillectomy may be effective in reducing postoperative
      morbidity in adjunct with classic analgesics.

PMID- 19393404
TI  - Test-retest reliability of drug-induced sleep endoscopy.
AB  - OBJECTIVE: To determine the test-retest reliability of drug-induced sleep
      endoscopy (DISE). METHODS: Prospective cohort study. Patients with OSA underwent
      two separate DISE examinations. The following outcomes were measured: a global
      assessment of obstruction at the palate and/or hypopharynx; the degree of
      obstruction at the palate and hypopharynx; and the contribution of individual
      structures (palate, tonsils, tongue, epiglottis, and lateral pharyngeal walls) to
      obstruction. RESULTS: Thirty-two patients underwent two separate DISE
      examinations. The preoperative sleep study apnea-hypopnea index was 40.7 +/-
      21.1, and the lowest oxygen saturation was 79.8 +/- 17.4 percent. Point estimates
      for the intraclass correlation coefficient analogs related to palatal obstruction
      ranged from 0.41 to 0.89; related to the hypopharyngeal airway, the point
      estimates ranged from 0.57 to 0.84. CONCLUSION: The test-retest reliability of
      DISE appears good, especially in the evaluation of the hypopharyngeal airway.
      Larger studies can generate more precise confidence interval estimates and test
      the generalizability of these findings.

PMID- 19393406
TI  - Reduction in surgical innovation, 1988 to 2006.
AB  - OBJECTIVE: We hypothesize that increasing regulation of human subject research
      has reduced the number of published reports of surgical innovation in
      otolaryngology. STUDY DESIGN: A systematic review of a predetermined subset of
      otolaryngology literature. METHODS: We randomly selected half of the articles
      published in 1988 and 2006 in three prominent journals. After identifying
      information was concealed, abstracts were classified independently by two authors
      into three groups: innovation, modification, or neither. Disagreements were
      resolved by a third author who read the entire article. Proportions were compared
      with chi(2) analysis. RESULTS: The proportion of articles classified as
      innovation or modification decreased significantly from 67 of 367 (18.3%) in 1988
      to 59 of 548 (10.8%) in 2006 (P = 0.001). The elimination of radiology and
      pathology quiz cases yielded similar results: 11.1 percent vs 18.9 percent, P =
      0.001. Innovation or modification in animal model research also decreased (0.9%
      vs 3.8%, P = 0.003). Overall, only 4 articles were actually classified as true
      innovation. CONCLUSIONS: The frequency of true innovation was low in both years,
      but articles that described surgical modifications decreased significantly over
      this 18-year period. One reason may be increased administrative barriers for
      clinical research approval. Although our analysis cannot determine cause and
      effect, it is an important finding that deserves further study.

PMID- 19393407
TI  - Gelatin sponge insertion into tympanostomy tubes: an in-vitro study to evaluate
      postoperative obstruction.
AB  - OBJECTIVE: To analyze the efficacy of gelatin sponge insertion into lumens of
      tympanostomy tubes to prevent obstruction in the presence of blood. STUDY DESIGN:
      In vitro model. METHODS: Absorbable gelatin sponge wicks were placed in the lumen
      of Ultrasil Collar Button ventilation tubes and Shepherd Grommet ventilation
      tubes. One half of each group was covered with blood, the other left untreated.
      Each tube was treated with ofloxacin solution three times daily for seven days.
      After treatment, the tubes were inspected. Reinspection was performed after brief
      suctioning. Numerical scores were given based on degree of obstruction. RESULTS:
      A statistically significant difference in degree of obstruction (P < 0.0001) was
      seen between all tubes with wicks alone versus those with blood added. After re
      evaluation, there remained a statistically significant difference between tubes
      with wicks alone and tubes with wicks and blood (P < 0.0001). CONCLUSIONS:
      Gelatin sponge insertion does not prevent, and may in fact, enhance, obstruction
      of pressure equalization tube lumens in the presence of blood.

PMID- 19393408
TI  - Imaging correlation of children with DFNB1 vs non-DFNB1 hearing loss.
AB  - OBJECTIVES: To evaluate temporal bone CT findings in GJB2-related deafness
      (DFNB1) hearing loss and non-DFNB1 hearing loss children. STUDY DESIGN: Case
      control series. SUBJECTS AND METHODS: Children with nonsyndromic hearing loss
      diagnosed as DFNB1 or non-DFNB1 after screening GJB2 allele variants and the
      large GJB6 deletion. Temporal bone CT images compared in a cohort of nine DFNB1
      children with 10 non-DFNB1 children. Visual criteria and absolute measurements
      were compared against established normative values. RESULTS: Visual inspection
      failed to identify two patients with abnormalities identified by using absolute
      measurements. Only one of nine DFNB1 children had an ear anomaly versus seven of
      10 non-DFNB1 (odds ratio 16.33; 95% CI, 1.35, 197.78; P = 0.050). The non-DFNB1
      group had a mean vestibule width that was significantly larger, and a mean
      lateral semicircular canal island width and vestibular aqueduct that were
      significantly smaller than the DFNB1 group. CONCLUSIONS: Visual inspection of
      temporal bone CT images alone may not identify all anomalies and should be used
      with absolute CT measurements. Abnormal temporal bone CT findings are
      significantly less likely in children with DFNB1 compared with non-DFNB1 children
      despite similar age and degree of hearing loss.

PMID- 19393409
TI  - A double-blind randomized controlled trial of management of recurrent nosebleeds
      in children.
AB  - BACKGROUND: To establish whether a treatment regimen of silver nitrate cautery
      and 4 weeks of antiseptic nasal cream is superior to antiseptic cream treatment
      alone in the management of pediatric epistaxis. STUDY DESIGN: Double-blind
      randomized controlled trial. SUBJECTS AND METHODS: Children with epistaxis and
      visible anterior septal vessels were invited to participate. Patients were
      randomized to receive treatment or control. Treatment patients received silver
      nitrate cautery, followed by antiseptic cream for 4 weeks. Control patients
      received sham cautery followed by antiseptic cream for 4 weeks. RESULTS: A total
      of 109 patients were randomized and results were available for 93 (85%). Of those
      receiving cautery, 21 (45.7%) of 46 had no bleeding in the 4 weeks before follow
      up. Of those receiving only antiseptic cream 14 (29.8%) of 47 had no bleeding.
      (chi(2) = 2.49; P = 0.114). More children in the active treatment group had an
      improvement in their symptoms compared with controls (42 of 46; 91.3%) in the
      treatment group vs 33 of 47 (70.2%) controls (chi(2) = 6.626; P = 0.01; relative
      risk reduction = 71 percent, number needed to treat = 4.7). CONCLUSION: When
      using subjective improvement in symptoms as the outcome measure, silver nitrate
      cautery with antiseptic cream twice daily for 4 weeks appears to give a small but
      statistically significant benefit when compared to antiseptic cream alone.

PMID- 19393410
TI  - Pediatric tonsil size: objective vs subjective measurements correlated to
      overnight polysomnogram.
AB  - OBJECTIVE: To compare subjective and objective tonsil size measurements (weight,
      volume, intertonsillar distance) along with simple pharyngeal measurements in the
      prediction of pediatric obstructive sleep apnea hypopnea syndrome (OSAHS)
      severity. STUDY DESIGN: Prospective case series. SUBJECTS AND METHODS: Tonsil
      size (0-4+) and Mallampati/Friedman palate position were subjectively measured.
      During adenotonsillectomy, tonsil size was objectively measured along with simple
      pharyngeal dimensions. Spearman rank correlation coefficients were calculated and
      forward and reverse stepwise multivariate regression modeling was used to assess
      the prediction of preoperative OSAHS severity as determined by polysomnogram
      (PSG). Evaluation of possible outlier influence was also performed. RESULTS:
      Thirty-four pediatric patients (median age, 4; range, 2-9) were included.
      Objective tonsil weight (Spearman's rho = 0.6143, P = 0.0002), tonsil volume (rho
      = 0.4960, P = 0.0039), and intertonsillar distance (rho = -0.7559, P < 0.0001)
      were strongly correlated with subjective tonsil size but not with age, body mass
      index (BMI), or preoperative apnea-hypopnea index (AHI). Regression modeling
      demonstrated that only measured tonsil weight (beta = 1.43, P = 0.003), age (beta
      = -3.21, P = 0.001), and hard palate length (beta = 0.979, P = 0.003) were
      significant predictors of the preoperative AHI (R(2) = 0.5358). Evaluation of
      possible outliers indicated tonsil weight was the most robust predictor of
      preoperative AHI. CONCLUSION: Subjective tonsil size measurements correlate well
      with objective tonsil volume measurements. However, only objective tonsil
      measurements were significantly predictive of objective PSG-measured OSAHS
      severity.

PMID- 19393411
TI  - Chorda tympani in chronic inflammatory middle ear disease.
AB  - OBJECTIVES: To study the effect of chronic inflammatory middle ear disease on
      gustatory function of chorda tympani nerve. METHODS: A prospective study was
      performed on 85 patients having unilateral chronic inflammatory middle ear
      disease of either cholesteatomatous or noncholesteatomatous type. Gustatory
      assessment on both sides of the tongue was performed using dry taste strips.
      RESULTS: Comparison of mean taste scores on the side of diseased ear vs normal
      ear was done. On the diseased side the mean taste score was 9.16 and on the
      normal side the mean taste score was 13.24. The difference between the two was
      found to be statistically significant (P < 0.0001). The results were also
      analyzed for various other parameters like type, duration, and location of
      disease. CONCLUSION: A patient with chronic inflammatory middle ear disease
      already has dysfunctional chorda tympani and is unlikely to notice a change in
      the taste sensation in the event of cutting of the nerve during the course of an
      ear surgery.

PMID- 19393412
TI  - Epitympanoplasty with mastoid obliteration technique: a long-term study of
      results.
AB  - OBJECTIVE: To report the long-term results of epitympanoplasty with mastoid
      obliteration technique. SUBJECTS AND METHODS: Two hundred adult cases had
      undergone epitympanoplasty with mastoid obliteration from December 1994 to May
      2003. The mean postoperative observation period was 91 months, with a minimum of
      five years. Epitympanoplasty with mastoid obliteration technique has four major
      procedures: the widening of the external auditory canal and removal of the
      scutum; preservation of the posterior canal wall; epitympanoplasty; and mastoid
      obliteration. We examined postoperative complications and hearing outcomes.
      RESULTS: There was no retraction pocket formation and recurrence of
      cholesteatoma. Residual cholesteatoma in the tympanic cavity was seen in 10 cases
      (5%) and three cases were seen in the mastoid cavity (1.5%). Other complications
      were otorrhea (15 cases), perforation (8 cases), material extrusion (6 cases),
      and posterior auricular infection (4 cases). The average preoperative pure tone
      air-bone gap, postoperative pure tone air-bone gap, and air-bone gap closure were
      31.5 +/- 12.4 dB, 25.3 +/- 12.2 dB, and 6.2 +/- 12.6 dB, respectively. There were
      significant differences between the preoperative and postoperative values (P <
      0.01). CONCLUSIONS: The authors believe that epitympanoplasty with mastoid
      obliteration technique can combine the advantages of canal wall down and canal
      wall up techniques while improving their shortcomings.

PMID- 19393413
TI  - Labyrinthitis ossificans: how accurate is MRI in predicting cochlear obstruction?
AB  - OBJECTIVE: To determine the accuracy of preoperative MRI in predicting cochlear
      obstruction in pediatric patients with a history of bacterial meningitis.
      METHODS: A case series with chart review was performed at a tertiary care
      multidisciplinary cochlear implant program. Forty-five children with hearing loss
      that resulted from bacterial meningitis were implanted from 1991 to 2006. Twenty
      five children had preoperative MRI with high-resolution axial T2-weighted images
      to assess for cochlear patency. RESULTS: Seventeen of 25 patients (68%) had
      surgical evidence of cochlear obstruction. Six patients (37.5%) required
      circummodiolar drill-outs, and one patient (6.25%) underwent placement of a
      double array cochlear implant. The nine remaining patients (56%) with cochlear
      obstruction required removal of fibrous tissue or drilling of the inferior basal
      turn, but did not require manipulation of the ascending basal turn to achieve
      full electrode insertion. The sensitivity, specificity, and positive and negative
      predictive value of MRI predicting intraoperative cochlear obstruction with 95
      percent confidence intervals was 94.1 percent (71-99), 87.5 percent (47-99), 94.1
      percent (71-99) and 87.5 percent (47-99), respectively. CONCLUSION: Preoperative
      high-resolution T2 MRI may be useful in predicting cochlear obstruction in
      patients with a prior history of bacterial meningitis.

PMID- 19393414
TI  - Intraoperative use of cone-beam computed tomography in a cadaveric ossified
      cochlea model.
AB  - OBJECTIVES: To describe a cadaveric temporal bone model of labyrinthitis
      ossificans and investigate the utility of intraoperative cone-beam computed
      tomography (CBCT) in the facilitating cochlear implantation. DESIGN: Cadaveric
      temporal bone study. METHODS: Five cadaveric heads had cement introduced into the
      10 cochleas. CBCT and a conventional CT scan were compared to assess the extent
      of cochlear obliteration. The cement was drilled-out (under CBCT guidance, if
      required) and cochlear implant electrode arrays (from 3 different manufacturers)
      inserted. RESULTS: CBCT images demonstrated temporal bone anatomy and the extent
      of cochlear obliteration as clearly as conventional CT in all cases.
      Intraoperative CBCT guided drilling and facilitated electrode placement in two of
      five heads (3 of 10 ears). Streak-artifact from the electrodes of two devices
      partially obscured image clarity. CONCLUSIONS: The obliterated cochlear model
      reproduced a disease-ossified cochlear both radiographically and surgically. CBCT
      is useful for intraoperative imaging to facilitate electrode array placement in
      the obliterated or congenitally abnormal cochlea.

PMID- 19393415
TI  - Randomized trial of tissue adhesive vs staples in thyroidectomy integrating
      patient satisfaction and Manchester score.
AB  - OBJECTIVE: Closure of skin incision of minimally invasive thyroidectomy with
      tissue adhesive is compared with surgical staples for 1) cosmetic appearance, 2)
      patient pain score, and 3) patient satisfaction score. STUDY DESIGN: Prospective
      single-blinded randomized study. SUBJECTS AND METHODS: Seventy-two patients
      undergoing minimally invasive thyroid surgery using video-assisted thyroidectomy
      (VAT) and minimal incision thyroidectomy (MIT) techniques were randomized for
      skin closure into two groups, one using staples and the other using tissue
      adhesive. Patients evaluated their pain on the first and tenth postoperative
      days. Scars were assessed using the Manchester scar assessment tool, and patients
      completed a satisfaction assessment form. RESULTS: Sixty out of the 72 patients
      were followed up for three months postoperatively. Assessment of wound cosmesis
      revealed no statistical difference; however, there was a statistical difference
      in ability to shower and overall satisfaction in the tissue adhesive group (P =
      0.017). CONCLUSION: Tissue adhesive is an excellent alternative for skin incision
      closure, having the added advantage of ability to shower on the same day,
      avoidance of the anxiety associated with staple removal, and no General
      Practitioner (GP) visit required for wound care. The use of tissue adhesive
      achieves higher patient satisfaction levels and enhances the perception of
      minimally invasive thyroid surgery (MITS) techniques among patients and surgeons
      alike.

PMID- 19393416
TI  - B-RAF V600E mutational analysis of fine needle aspirates correlates with
      diagnosis of thyroid nodules.
AB  - OBJECTIVE: A mutation of B-type RAF kinase (B-RAF) represents the most common
      genetic alteration in papillary thyroid cancer (PTC), possibly signifying a more
      aggressive biology. Fine needle aspiration (FNA) represents the most useful
      initial diagnostic tool of thyroid nodules. Molecular analysis of the mutation
      status of B-RAF in thyroid nodule FNAs may provide guidance for treatment
      planning. STUDY DESIGN: Cross-sectional study. SUBJECTS AND METHODS: A
      retrospective chart review was undertaken for clinically relevant data of
      papillary thyroid cancer (PTC), follicular variant of PTC (FV-PTC), and
      nonmalignant goiters. After blinded pathologic review, histologic and cytologic
      samples were analyzed by LightCycler PCR (LCPCR) with allele-specific fluorescent
      probe melting curve analysis (FMCA) for the V600E mutation of B-RAF. RESULTS: Of
      the 45 patient samples analyzed, B-RAF mutation was found to be significantly
      higher in papillary carcinomas when compared to follicular variant of papillary
      thyroid carcinomas (55.6% vs 14.3%, P = 0.05). Pathologic B-RAF mutational status
      significantly correlated with cytologic B-RAF mutational status (P < 0.0001),
      cytologic interpretation (P = 0.012), and histologic diagnosis (P = 0.011).
      CONCLUSIONS: Determination of B-RAF V600E mutation of thyroid nodule FNAs by
      LCPCR may be a useful tool to guide treatment planning. These data support
      investigating the utility of this molecular marker in a prospective manner.

PMID- 19393417
TI  - Fine-needle aspiration biopsies in the management of indeterminate follicular and
      Hurthle cell thyroid lesions.
AB  - OBJECTIVES: To determine the value of fine-needle aspiration biopsies (FNABs) of
      the thyroid and stratify the risk of malignancy within the indeterminate FNAB
      diagnostic category at our institution. STUDY DESIGN: Case series with chart
      review of preoperative FNABs of consecutive patients who underwent total
      thyroidectomy between 2005 and 2007. SUBJECTS AND METHODS: A total of 115 cases
      were reviewed, and FNABs were categorized into four groups: benign, positive or
      suspicious for malignancy, indeterminate (follicular or Hurthle cell lesions),
      and nondiagnostic. Cytohistologic correlation was then established. RESULTS: The
      accuracy of FNAB in detecting thyroid malignancy was 88 percent with false
      negative and false-positive rates of 13 percent and 7 percent, respectively.
      Overall, 52 percent of the indeterminate cases were carcinomas (48 percent of
      follicular lesions and 62 percent of Hurthle cell lesions). In the presence of
      cytologic atypia, the rate of malignancy increased to 75 percent and 83 percent
      for the follicular and Hurthle cell lesions, respectively. CONCLUSIONS: FNAB is
      an accurate and helpful method for the evaluation of thyroid nodules with results
      directly correlating with management. Surgery should be considered for FNABs
      categorized as indeterminate, especially in the presence of cytologic atypia.
      Because of the high false-negative rate, benign FNABs require close follow-up
      with ultrasound examination and periodic biopsies.

PMID- 19393418
TI  - Effectiveness of topically applied halofuginone in management of subglottic
      stenosis in rats.
AB  - OBJECTIVE: The aim of the study is to ascertain the antifibrotic effect of
      topically applied halofuginone after acute subglottic injury. MATERIALS AND
      METHODS: After standardized trauma to subglottic area, rats were divided into two
      groups: the study group that received treatment and the control group that did
      not. The subjects were treated with topical application of cottonoid soaked in 30
      mg/dL halofuginone solution for 5 minutes after subglottic trauma. The larynx
      specimens were examined histopathologically by light microscopy to assess
      fibrosis, epithelialization, inflammation, and necrosis. RESULTS: The fibrosis
      indexes of the treated group were significantly less than those of the control
      group (P < 0.05). CONCLUSIONS: Topically applied halofuginone hydrobromide
      decreases fibrosis/scar tissue formation secondary to experimentally induced
      acute subglottic trauma.

PMID- 19393419
TI  - Chromosomal changes in sporadic and familial head and neck paragangliomas.
AB  - OBJECTIVE: Paragangliomas (PGLs) of the head and neck are benign neoplasms
      derived from the autonomic nervous system. Familial PGLs have been associated
      with germline mutations in succinate dehydrogenase (SDH) genes, and occasionally
      in Von Hippel-Lindau (VHL) and RET. The aim of this study was to compare somatic
      DNA copy number changes in tumors of familial and sporadic origin. MATERIAL AND
      METHODS: Eight familial and 16 sporadic patients were analyzed for germline
      mutations and exon deletions in SDHB, SDHC, SDHD, VHL, and RET by direct
      sequencing and MLPA. Microarray CGH analysis was applied to map genome-wide
      somatic copy number changes. RESULTS: Fifteen cases carried a germline mutation
      in SDHB or SDHD, four of which not described before. Microarray CGH detected
      abnormalities in 10 of 18 cases, most frequently concerning deletions at 1p, 1q,
      and 11q, the sites where SDH are located. However, these deletions occurred in
      both SDH mutation-positive and SDH mutation-negative cases. CONCLUSIONS: These
      data suggest that inactivating germline SDH mutations and somatic deletions of
      SDH genes as a "second hit" are involved in a subset, but not in all PGLs.
      Additional genes and mechanisms may need to be studied, especially in the group
      of sporadic PGL showing no chromosomal aberrations.

PMID- 19393420
TI  - Surgical debridement and adjunctive hyperbaric oxygen in cervical necrotizing
      fasciitis.
AB  - OBJECTIVE: To review our management of cervical necrotizing fasciitis (CNF) with
      the use of adjunctive hyperbaric oxygen therapy (HBO). STUDY DESIGN: Case series
      with chart review. SUBJECTS AND METHODS: Evaluation of ten patients with CNF
      between 2001 to 2006. RESULTS: There were five male and six female patients. Mean
      age was 43 +/- 11 years. Eight cases resulted from an odontogenic source.
      Comorbidities included diabetes mellitus, hypertension, and substance abuse. All
      patients had computed tomography scans performed, received intravenous
      antibiotics, and underwent surgical debridement. Eight patients underwent surgery
      within 24 hours. The average number of debridements was 2.2 +/- 0.8.
      Hospitalization was twice as long for diabetic patients (15.5 +/- 8.16 days)
      compared with nondiabetic patients (7.5 +/- 1.6 days, P = 0.029). Nine patients
      had HBO therapy. Combined data revealed a possible decrease in length of
      hospitalization with HBO therapy (P < 0.001). No mortality was documented.
      CONCLUSION: In addition to early and aggressive medical management and surgical
      debridement, this study suggests that HBO therapy is a beneficial adjunct by
      potentially decreasing length of hospitalization. Randomized trials are still
      needed to demonstrate its efficacy.

PMID- 19393421
TI  - Radiologic staging system for allergic fungal rhinosinusitis (AFRS).
AB  - OBJECTIVES: 1) Develop an objective method for quantifying radiologic bone
      erosion in allergic fungal rhinosinusitis (AFRS); and 2) assess the utility of
      the new CT scan staging system in differentiating AFRS patient groups. METHODS:
      Patients from two tertiary care rhinology practices with AFRS and available CT
      scans (1999-2007) were included for review by trained graders. The following
      novel assessment scale was used: Each paranasal sinus wall with expansion/erosion
      was scored 1 point, with maximum 3 points possible for each frontal sinus, 2
      points for each ethmoid complex, 3 points for each sphenoid sinus, 3 points for
      each maxillary sinus, and 1 point each for the frontal and sphenoid intersinus
      septae, yielding maximum of 24 possible points. RESULTS: A total of 111 CT scans
      were reviewed. Mean score was 7.8 (range, 0-24). Males scored significantly
      higher than females (mean, 9.3 vs 5.6, P = 0.001). African Americans scored
      significantly higher than Caucasians (mean, 9.6 vs 5.0, P < 0.001). CONCLUSIONS:
      A scoring system for bone remodeling in AFRS is presented. Males and African
      Americans with AFRS demonstrate significantly more bone erosion. Additional
      analysis of disease course will assess the utility of this staging system in
      predicting outcomes.

PMID- 19393422
TI  - Polymorphisms in the interleukin-22 receptor alpha-1 gene are associated with
      severe chronic rhinosinusitis.
AB  - RATIONALE: Stimulation of interleukin-22 receptor alpha-1 (IL22RA1) was reported
      to increase the innate immune responses in inflammatory diseases. Moreover, a
      reduced level of IL22RA1 was found in patients with recalcitrant CRS with nasal
      polyps. OBJECTIVE: To explore association between single nucleotide polymorphisms
      (SNPs) in IL22RA1 and severe CRS. METHODS: We extracted DNA from 206 cases with
      severe CRS and 196 postal code-matched controls. Twenty-three SNPs in the IL22RA1
      gene were selected from the pooling-based genome-wide association study and from
      the CEU HapMap dataset and genotyped. PLINK software was used to determine
      association. RESULTS: After Bonferroni correction, three SNPs (rs4292900 P(nom) =
      0.0006, OR = 1.757; rs4648936 P(nom) = 0.0011, OR = 1.716; rs16829225 P(nom) =
      0.0014, OR = 1.977) show significant differences in allelic frequencies between
      cases and controls. CONCLUSION: Polymorphisms in IL22RA1 are associated with
      severe CRS. Replication and functional studies are involved to better understand
      the mechanism by which these polymorphisms contribute to the pathogenesis of CRS.

PMID- 19393423
TI  - The comparison of histopathological characteristics of polyps in asthmatic and
      nonasthmatic patients.
AB  - INTRODUCTION: Considering the different clinical aspects of polyps in asthmatic
      and nonasthmatic patients, we aimed to explore their histopathological
      characteristics. MATERIAL AND METHODS: Twenty-five asthmatic patients and 25
      nonasthmatic patients with polypoid chronic rhinosinusitis (29 male, 21 female;
      mean age 41.3 +/- 13.27; range 15-78 years) were enrolled in the study to be
      compared on the basis of histopathological characteristics. They were compared
      according to the following seven light microscopic findings: basement membrane
      thickness, goblet cell hyperplasia, subepithelial edema, submucous gland
      formation, eosinophilic infiltration, lymphocytic infiltration, and
      polymorphonuclear infiltration. RESULTS: Basement membrane thickening, goblet
      cell hyperplasia, and eosinophilic and lymphocytic infiltration were more
      prominent in the asthmatic compared with the nonasthmatic group (P < 0.05),
      whereas polymorphonuclear infiltration was more prominent in nonasthmatics (P <
      0.05). No statistically significant differences were found between the two groups
      with regard to submucosal gland hyperplasia or subepithelial edema. CONCLUSION:
      Asthmatic patients present histopathological characteristics of a marked chronic
      inflammatory reaction, which might explain the negative effect on chronic
      rhinosinusitis outcome and the severity of the disease in this group.

PMID- 19393424
TI  - Arytenoid prolapse: a source of obstruction following laryngotracheoplasty.
AB  - OBJECTIVE: Arytenoid prolapse is a potential source of upper airway obstruction
      following laryngotracheoplasty, and may be difficult to identify. We explored the
      incidence, clinical features, etiology, and surgical approach to patients with
      arytenoid prolapse following laryngotracheoplasty. STUDY DESIGN: Case series with
      chart review. SUBJECTS AND METHODS: The charts of 93 patients diagnosed with
      arytenoid prolapse following laryngotracheoplasty from 1981 to 2007 were
      reviewed. RESULTS: The incidence was 5.7 percent (93/1634). Forty-nine patients
      had unilateral prolapse; 44 had bilateral prolapse. Average time from
      laryngotracheoplasty to presentation was 36.8 months. Common symptoms were
      dyspnea on exertion, tracheostomy dependence, and sleep-disordered breathing.
      Fifty-four patients (58%) required surgical intervention, with arytenoid
      reduction performed in 45 patients. Nine underwent reduction during revision
      laryngotracheoplasty or cricotracheal resection. Fourteen patients required a
      second procedure for persistent prolapse. Thirty-nine (42%) required no
      intervention. Symptom resolution or decannulation was achieved in all patients in
      whom prolapse was the source of obstruction. Statistically significant
      differences were found when anterior vs posterior graft utilization was compared.
      CONCLUSIONS: Arytenoid prolapse is a cause of airway obstruction following
      laryngotracheoplasty. Subtle airway complaints and decannulation failures are
      common features. Both endoscopic and open procedures can successfully treat
      arytenoid prolapse. Potential etiologies are discussed.

PMID- 19393425
TI  - Extracellular matrix gene expression during wound healing of the injured rat
      vocal fold.
AB  - OBJECTIVES: To measure the expression of procollagen-I and -III, decorin, and
      hyaluronan synthase (HAS)-1, -2, and -3 during the inflammatory, proliferative,
      and remodeling phases of rat vocal fold injury. STUDY DESIGN: Prospective, animal
      model. SUBJECTS AND METHODS: Vocal folds were injured in 30 rats. Injured
      specimens were harvested on postinjury days 1, 3, 7, 14, 28, and 56. Five
      uninjured rats were used for polymerase chain reaction (PCR) control. Real-time
      PCR was used to measure the expression of procollagen-I and -III, decorin, and
      hyaluronan synthase (HAS)-1, -2, and -3. RESULTS: Compared with control,
      expression of procollagen-I and -III were significantly decreased on postinjury
      days 1 and 56; decorin expression was significantly decreased on postinjury days
      1, 3, 7, and 56; HAS-1 expression was significantly decreased on postinjury days
      3, 7, 14, 28, and 56; HAS-2 expression was significantly decreased on postinjury
      days 28 and 56; HAS-3 expression was significantly decreased on postinjury day
      56. CONCLUSIONS: Results revealed time-dependent alterations in the expression of
      genes coding procollagen-I and -III, decorin, and HAS-1, -2, and -3. Knowledge of
      the temporal regulation of these genes and underlying histology will be used in
      future studies to investigate molecular approaches for manipulation of vocal fold
      injury.

PMID- 19393426
TI  - The ethmo-frontal angle: a new anatomic and radiologic landmark for use in sinus
      surgery.
AB  - OBJECTIVE: To identify anatomic and radiologic landmarks to assist with frontal
      sinus surgery. STUDY DESIGN: Retrospective review. SUBJECTS AND METHODS: Sinus CT
      scans of 50 patients were evaluated with respect to a new radiologic and anatomic
      landmark, the ethmo-frontal angle (EFA). RESULTS: Right-sided EFA ranged from 135
      to 171 degrees. Left-sided EFA ranged from 136 to 167 degrees. Measurements of
      both sides displayed a normal distribution. When right and left sides within
      individuals were compared, there was no correlation to indicate a high degree of
      variation between any particular patient's right and left side EFA. CONCLUSION:
      The EFA is a new landmark to assist otolaryngologists during surgery on and
      around the frontal sinus. Normal values for this angle have been presented.
      Surgeons should be aware that asymmetry in a patient's EFA is common, and each
      side should be examined individually.

PMID- 19393427
TI  - Pedunculated capillary hemangioma of the external ear.

PMID- 19393428
TI  - Tympanic membrane eczema.

PMID- 19393429
TI  - Choristoma of the parotid gland.

PMID- 19393430
TI  - An unusual high-velocity large metal object concealed in the nasal septum.

PMID- 19393431
TI  - The additional role of virtual endoscopy in the diagnosis of superior
      semicircular canal dehiscence.

PMID- 19393432
TI  - Virtual endoscopy has a limited role in the diagnosis of superior semicircular
      canal dehiscence.

PMID- 19393433
TI  - Endoscopic sinus surgery and evidence-based medicine: a judgment revised.

PMID- 19393434
TI  - Response to: "Better research for better healthcare" promoting high quality
      clinical research, not biased personal enthusiasm.

PMID- 19393468
TI  - Quiz page May 2009: Lymphaticourinary fistula causing chyluria and nephrotic
      range proteinuria.

PMID- 19393469
TI  - Statin effects in CKD: is there a "point of no return"?

PMID- 19393470
TI  - Kidney damage in metabolic syndrome: nip it in the bud.

PMID- 19393471
TI  - Focusing on health literacy might help us cross the quality chasm.

PMID- 19393472
TI  - C-reactive protein, statins, and cardiovascular risk: what can JUPITER teach us?

PMID- 19393473
TI  - Effect of pamidronate on bone loss after kidney transplantation: a randomized
      trial.
AB  - BACKGROUND: Kidney transplantation is associated with an increased risk of bone
      fracture and rapid loss of bone mineral density after kidney transplantation.
      STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: Patients were
      randomly assigned to treatment (n = 46) or control (no treatment; n = 47) groups.
      Patients were stratified according to parathyroid hormone level and sex. Those
      with parathyroid hormone level less than 150 pg/mL were excluded. INTERVENTION:
      The treatment and control groups received pamidronate, 1 mg/kg, perioperatively
      and then at 1, 4, 8, and 12 months or no treatment, respectively. All received
      calcium (500 mg) and vitamin D (400 units) daily. Immunosuppression was
      cyclosporine and prednisolone, with no difference in dosing between the 2 groups.
      OUTCOMES & MEASUREMENTS: Bone mineral density was evaluated by means of dual
      energy x-ray absorptiometry of the lumbar spine and hip at baseline and 3, 6, 12,
      and 24 months, with the primary end point at 1 year of percentage of change in
      bone mineral density from baseline. Clinical fractures were recorded and also
      evaluated by means of spinal radiographs at baseline and 1 and 2 years. RESULTS:
      Pamidronate protected bone mineral density at the lumbar spine; bone mineral
      density increased by 2.1% in the treatment group and decreased by 5.7% in the
      control group at 12 months (P = 0.001). Protection was also seen in Ward's area
      of the hip (P = 0.002) and the total hip (P = 0.004). There was no difference in
      femoral neck bone mineral density loss between the 2 groups. Fracture rates in
      the treatment and control groups were 3.3% and 6.4% per annum, respectively.
      LIMITATIONS: This study was not powered to detect differences in fracture rates.
      CONCLUSION: Pamidronate protects against posttransplantation bone loss at the
      lumbar spine and Ward's area of the hip.

PMID- 19393474
TI  - Plasma and peritoneal dialysate levels during daptomycin therapy for peritonitis.

PMID- 19393475
TI  - [European week for vaccination].

PMID- 19393476
TI  - Routine transthoracic echocardiography in a general Intensive Care Unit: an 18
      month survey in 704 patients.
AB  - The authors analyzed 704 transthoracic echocardiographic (TTE) examinations,
      performed routinely to all admitted patients to a general 16-bed Intensive Care
      Unit (ICU) during an 18-month period. Data acquisition and prevalence of
      abnormalities of cardiac structures and function were assessed, as well as the
      new, previously unknown severe diagnoses. A TTE was performed within the first 24
      h of admission on 704 consecutive patients, with a mean age of 61.5+/-17.5 years,
      ICU stay of 10.6+/-17.1 days, APACHE II 22.6+/-8.9, and SAPS II 52.7+/-20.4. In
      four patients, TTE could not be performed. Left ventricular (LV) dimensions were
      quantified in 689 (97.8%) patients, and LV function in 670 (95.2%) patients.
      Cardiac output (CO) was determined in 610 (86.7%), and mitral E/A in 399 (85.9%
      of patients in sinus rhythm). Echocardiographic abnormalities were detected in
      234 (33%) patients, the most common being left atrial (LA) enlargement (n=163),
      and LV dysfunction (n=132). Patients with these alterations were older (66+/-16.5
      vs 58.1+/-17.4, p<0.001), presented a higher APACHE II score (24.4+/-8.7 vs
      21.1+/-8.9, p<0.001), and had a higher mortality rate (40.1% vs 25.4%, p<0.001).
      Severe, previously unknown echocardiographic diagnoses were detected in 53 (7.5%)
      patients; the most frequent condition was severe LV dysfunction. Through a
      multivariate logistic regression analysis, it was determined that mortality was
      affected by tricuspid regurgitation (p=0.016, CI 1.007-1.016) and ICU stay
      (p<0.001, CI 1-1.019). We conclude that TTE can detect most cardiac structures in
      a general ICU. One-third of the patients studied presented cardiac structural or
      functional alterations and 7.5% severe previously unknown diagnoses.

PMID- 19393477
TI  - A simple prognostic score for risk assessment in patients with acute
      pancreatitis.
AB  - BACKGROUND: Acute pancreatitis (AP) is a common disease that poses potential
      serious problems. Its clinical course is often unpredictable. Identification of
      high risk patients enables early appropriate treatment. METHODS: We conducted a
      prospective study to develop a new prognostic method that can objectively and
      easily grade the severity of AP within the first 72 h of admission. The
      prediction rule was based on clinical and analytical parameters in 308 patients
      admitted in a community-based hospital. We validated the score in 193 additional
      patients in the same hospital. RESULTS: Independent prognostic factors related to
      poor prognosis were age >65 years, leucocytes >13,000/mm(3), albumin <2.5 mg/dL,
      calcium <8.5 mg/dL and reactive C protein >150 mg/dL. We assigned points to each
      of the independent factors for complicated AP in proportion to the regression
      coefficients. We defined three different risk groups according to the points
      obtained in the prediction rule. Low risk, 0 points (18% patients, 0% risk),
      moderate, 1-3 points (56% patients, 19% risk) and high, 4-6 points (26% patients,
      73% risk). The sensitivity of this formula was 90% with specificity of 63%. The
      positive and negative predictive values were 50% and 94% respectively.
      CONCLUSIONS: Our simple prediction rule is an additional tool that may help
      physicians stratifying the severity of AP. Patients with high risk for
      complicated AP should be kept under close surveillance whereas low risk patients
      would not need special monitoring.

PMID- 19393478
TI  - Corynebacterium striatum--a classic pathogen eluding diagnosis.
AB  - We report one case of infective endocarditis and two cases of arthritis due to
      Corynebacterium striatum. After reviewing all previously reported cases, we
      illustrate the clinical features typical of infection, including nosocomial risk
      factors and prominent embolic phenomena in the cases of endocarditis. Our cases
      underscore the importance of prompt diagnosis when confronted with positive blood
      and synovial cultures. This ubiquitous organism and common contaminant is a rare
      yet deadly pathogen.

PMID- 19393479
TI  - Abnormalities in aminotransferase levels during acute pyelonephritis.
AB  - Liver abnormalities are common in septic patients. The study was aimed at
      investigating the alterations in aminotransferase levels during acute
      pyelonephritis in adults. Serum aminotransferases (AST and ALT) were determined
      in 421 patients (aged 16-90 years, 79.8% females) admitted to the hospital
      because of acute pyelonephritis. Abnormally high aminotransferase (sAST or sALT)
      levels were present in 21.4% (95% CI 17.6-25.9%) of patients without pre-existing
      liver disease (n=401). Aminotransferase abnormality was moderate in the majority
      of cases. After adjusting for confounders, aminotransferase abnormality was
      associated with age and with signs of sepsis (particularly, high body temperature
      and low blood pressure). Aminotransferase levels tended to normalize during
      convalescence. In conclusion, the management of patients with pyelonephritis
      should take into account that moderate and self-limited abnormalities in
      aminotransferase levels are frequent during the acute phase of the disease.

PMID- 19393480
TI  - Efficacy and safety of Monascus purpureus Went rice in children and young adults
      with secondary hyperlipidemia: a preliminary report.
AB  - BACKGROUNDS/AIMS: Nephrotic dyslipidemia is a risk factor for development of
      systemic atherosclerosis; also it may aggravate glomerulosclerosis and enhance
      progression of glomerular disease. We aimed to assess the efficacy and safety of
      Monascus purpureus Went rice vs. fluvastatin therapy in the management of
      nephrotic dyslipidemia. METHODS: Seventy-two patients with idiopathic persistent
      nephrotic syndrome with secondary dyslipidemia were included. They were randomly
      allocated into 3 - age and sex - matched groups. The first group comprised of 20
      cases and were given Monascus purpureus Went rice, second group comprised 30
      cases were given fluvastatin. The remaining 22 received no anti-dyslipidemic
      therapy and constituted a control group. All of these patients were subjected to
      thorough laboratory investigations including renal function tests, lipogram and
      neurological assessment. RESULTS: Our results showed that both fluvastatin and
      Monascus purpureus Went rice were well-tolerated with no significant side
      effects. Both of them significantly reduced cholesterol after 6 months and 1
      year. In comparison to baseline values, fluvastatin achieved a significant and
      progressive reduction of serum cholesterol by 35%, 38% and 42% at 3 months, 6
      months and after 1 year respectively (p<0.001). Similar reductions were observed
      in the Monascus purpureus Went rice group. After one year we observed that serum
      cholesterol was significantly lower in statin and Monascus purpureus Went rice
      groups compared to the control group. CONCLUSION: Monascus purpureus Went rice is
      safe, effective cholesterol lowering agent for nephrotic dyslipidemia both in
      adults and children.

PMID- 19393481
TI  - Selective defect of anti-pneumococcal IgG in a patient with persistent polyclonal
      B cell lymphocytosis.
AB  - BACKGROUND: Persistent polyclonal B cell lymphocytosis (PPBL) is a rare condition
      characterized by increased IgM and large excess of B cells with an IgD(+) CD27(+)
      phenotype. In normal individuals, these cells play a central role in the defense
      against pneumococcal infection. So far, few studies have characterized humoral
      immune responses in PPBL patients. We therefore measured IgG directed against S.
      pneumoniae antigens in a 51 yr-old woman with PPBL before and after vaccination
      with a pneumococcal 23-valent polysaccharide vaccine. METHODS: Antibodies against
      pneumococcal antigens were measured first with an overall immunoassay using
      microplates coated with the 23-valent pneumococcal vaccine. A serotype-specific
      test was also performed according to the WHO consensus protocol. RESULTS: Despite
      a large number of IgD(+) CD27(+) cells, our patient had low baseline titers of
      IgG directed against pneumococcal antigens and did not significantly respond to a
      23-valent polysaccharide vaccine against S. pneumoniae. On the contrary, she had
      good titers of IgG directed against tetanus toxoid. CONCLUSION: IgM(+) IgD(+)
      CD27(+) cells which accumulate in this patient with typical PPBL patient failed
      to perform IgG isotype switch after a polysaccharide vaccine. The potential
      mechanisms and relationships with the main features of PPBL are discussed.
      Further studies on a larger number of similar patients are needed.

PMID- 19393482
TI  - An audit of tumour marker utilization in Greece.
AB  - INTRODUCTION: Several international organizations have published guidelines for
      the correct use of tumour markers in clinical practice. However, there are
      reports that clinicians do not adhere to these guidelines in clinical practice.
      The present study constitutes an audit of TM use in a major hospital in Northern
      Greece. Purpose of our study is to quantify the magnitude of inappropriate TM
      requests as well as the corresponding financial cost. METHODS: We examined
      retrospectively all TM requests between 10/2006 and 07/2007 in the department of
      biochemistry of our hospital. The tumour markers included in our study were: CA
      19-9, CA 125, CA 15-3, AFP, NSE, CYFRA 21-1 and CEA. RESULTS: We found 9782
      inappropriate TM orders. For five of them - namely CA 125, AFP, CA 19-9, CYFRA 21
      1 and NSE - the proper requests were below 10%. There were 5.6 TM requests per
      patient. The total cost for inappropriate TM reached 239,748 euro, which
      corresponds to a monthly cost of 23,974euro. CONCLUSIONS: There is considerable
      inappropriateness in the utilization of TM in Greece which corresponds to
      significant financial cost. Various measures should be applied in order to
      increase the cost-effectiveness of TM use.

PMID- 19393483
TI  - Haemodialysis followed by continuous veno-venous haemodiafiltration in lithium
      intoxication; a model and a case.
AB  - For severe lithium intoxication haemodialysis is recommended to lower serum
      lithium levels rapidly. Frequently, serum lithium levels rebound after dialysis
      and repeated dialysis is needed. This is the first report of an adult patient
      with severe lithium intoxication who underwent haemodialysis (HD) followed by
      continuous veno-venous haemodiafiltration (CVVHDF). Mean lithium clearances with
      HD and CVVHDF were 173 and 61 ml/min, respectively. Serum lithium levels were
      rapidly lowered and did not rebound. Two compartment simulations illustrate that
      HD followed by CVVHDF is the most effective strategy for removing lithium from
      the intracellular compartment.

PMID- 19393484
TI  - Severe migraine attacks during treatment of chronic hepatitis C.

PMID- 19393485
TI  - Polyuria and polydipsia following an intra-articular steroid injection.

PMID- 19393486
TI  - Papular rash in the hand: a case report of atrial myxoma.

PMID- 19393487
TI  - Syphilitic periostitis.

PMID- 19393488
TI  - Online publication of original articles.

PMID- 19393489
TI  - Glucoregulation in type 2 diabetes: the lower the better? Glycosylated HbA1c of
      6.5% seems to be the limit.

PMID- 19393490
TI  - Systemic lupus erythematosus and vaccination.
AB  - Patients with systemic lupus erythematosus (SLE) are frequently immunodepressed
      making them more vulnerable to infections. Preventive vaccination is therefore
      warranted but has often been withheld owing to fears of a link between infection
      and autoimmunity, and the possibility of inducing or exacerbating lupus after
      vaccination. The data published in the literature suggest that vaccination of
      lupus patient is safe, except for live vaccines. Their efficacy is lower than in
      healthy subjects but protection seems to be sufficient. But further large-scale
      studies are required to confirm these statements.

PMID- 19393491
TI  - Genetic susceptibility to systemic sclerosis from clinical aspect to genetic
      factor analyses.
AB  - BACKGROUND: Systemic sclerosis is a rare autoimmune disease mainly characterized
      by vascular alteration and fibrosis involving skin but also visceral organs such
      as lungs, digestive tract, and heart. This disease leads to high morbidity and
      mortality. Its pathogenesis remains unclear, but recent attention has focus on
      genetic factors. OBJECTIVE: We first recall the main manifestations associated
      with systemic sclerosis and leading to its diagnosis and prognosis. Then we
      propose an overview on human genetics studies, as a number of genetic loci have
      been identified that appear to be associated with the disease. METHODS: Articles
      concerning association studies with candidate genes encoding for extracellular
      matrix proteins, cytokines, growth factors, chemokines, and proteins involved in
      vascular tone and immune regulations are presented and discussed.
      RESULTS/CONCLUSION: Systemic sclerosis is a multigenic complex disorder. Genetic
      associations are observed in distinct phenotypes such as the diffuse cutaneous
      form or the limited form, or in association with specific autoantibody pattern.
      Promising candidate genes are those involved in pathways that lead to the
      vascular damage and fibrosis. A better knowledge of crucial mediators involved in
      systemic sclerosis could in the future provide new therapeutic strategies to
      control the disease.

PMID- 19393492
TI  - The role of inflammation on atherosclerosis, intermediate and clinical
      cardiovascular endpoints in type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with increased
      cardiovascular morbidity and mortality. Sub-clinical systemic inflammation is
      often present in T2DM patients. Systemic inflammation has also been implicated in
      the pathophysiology of atherosclerosis. This review investigates the direct
      evidence present in literature for the effect of inflammation on atherosclerosis,
      specifically in the setting of T2DM. Special emphasis is given to the
      pathogenesis of atherosclerosis as well as intermediate and clinical
      cardiovascular endpoints. The important role of deteriorated endothelial function
      in T2DM was excluded from the analysis. METHODS: Extensive literature searches
      were performed using the PubMed and Web of Science databases. Articles were
      identified, retrieved and accepted or excluded based on predefined criteria.
      RESULTS: Substantial evidence was found for an important inflammatory component
      in the pathogenesis of atherosclerosis in T2DM, demonstrated by inflammatory
      changes in plaque characteristics and macrophage infiltration. Most epidemiologic
      studies found a correlation between inflammation markers and intermediate
      cardiovascular endpoints, especially intima-media thickness. Several, but not all
      clinical trials in T2DM found that reducing sub-clinical inflammation had a
      beneficial effect on intermediate endpoints. When regarding cardiovascular events
      however, current literature consistently indicates a strong relationship between
      inflammation and clinical endpoints in subjects with T2DM. CONCLUSION: Current
      literature provides direct evidence for a contribution of inflammatory responses
      to the pathogenesis of atherosclerosis in T2DM. The most consistent relation was
      observed between inflammation and clinical endpoints.

PMID- 19393493
TI  - Progressive multifocal leukoencephalopathy, a review and an extended report of
      five patients with different immune compromised states.
AB  - Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of
      the brain caused by the JC-virus. Both a decreased cellular or humoral immune
      response can increase the susceptibility for JC-virus induced PML. Not only HIV
      infected people are at risk, a wide range of otherwise immune compromised
      patients are a potential target for this virus. This report of five PML patients
      shows the importance of a clinician's familiarity with this disease and it's
      presenting symptoms. The presenting symptoms of PML can sometimes mimic worsening
      of the underlying disease. Although different therapeutic strategies have been
      tried, the outcomes remain very poor. In this series, treatment with cidofovir
      appears not to be effective in treating PML, neither in HIV positive nor HIV
      negative patients. Experimental therapy with leflunomide, after tapering of the
      immunosuppressive medication, did change the natural course of PML in one
      patient.

PMID- 19393494
TI  - Diagnostic approach of pulmonary disease in the HIV negative immunocompromised
      host.
AB  - The advances in medicine have resulted in increasing number of immunocompromised
      patients with complications related to their underlying disease or the treatment
      of these conditions. Pulmonary infectious and non-infectious conditions are a
      major cause of morbidity and mortality in these patients, and represent a
      diagnostic challenge. This article reviews the major conditions causing pulmonary
      symptoms in the HIV negative immunocompromised host. It also discusses the role
      of the different diagnostic methods, including the recent advances in non
      invasive studies, in reaching a diagnosis of pulmonary disease in this patient
      population.

PMID- 19393495
TI  - Survey of cardiovascular risk factors in overweight and obese patients (SCOOP
      study) six-month changes in risk factor levels and cardiovascular risk.
AB  - BACKGROUND: Obesity is considered a major threat to health worldwide, and its
      treatment is difficult. The SCOOP project is aimed at describing the effects of
      treating obesity in everyday clinical practice, following a standard protocol of
      weight reduction. METHODS: A total of 2472 obese or overweight men and women
      (with a body mass index of 27 units or more), aged between 35 and 74, were
      enrolled in different clinical facilities. Treatment included a 25% average
      reduction in caloric intake and a recommendation to take a brisk walk for at
      least 150 min per week. After 6 months, a second survey was then carried out.
      RESULTS: At the entry examination, patients exhibited high levels of most
      cardiovascular risk factors and estimated cardiovascular risks, and a high
      prevalence of cardiovascular diseases (14.1% in men; 6.3% in women), diabetes
      (30.5% in men; 25.2% in women) and metabolic syndrome (25.6% in men; 22.8% in
      women). After 6 months, 69% of all enrolled patients reported for a final
      examination. Levels of all cardiovascular risk factors were significantly
      reduced, including estimated cardiovascular risks (-20.4% in men and -12.6% in
      women). A targeted 10% reduction in body weight was achieved by 19% of patients.
      Changes in weight and cardiovascular risk factors were highly correlated with the
      self-reported compliance to prescriptions, and graded with the observed weight
      reduction. Benefits should be lowered by 30% if it is assumed that the patients
      who did not show up at the follow-up did not change their characteristics.
      CONCLUSION: Short term positive effects of treatment of obesity can be obtained
      in everyday clinical practice using a simple protocol.

PMID- 19393496
TI  - Not all obese subjects of multiethnic origin are at similar risk for developing
      hypertension and type 2 diabetes.
AB  - BACKGROUND: Whether insulin resistance and not obesity per se is the major
      contributor to clinical outcomes associated with obesity has not been fully
      established. This study evaluated in a group of obese Brazilians of multiethnic
      origin to what extent the prevalence of hypertension and other cardiometabolic
      risk factors varies as a function of the degree of insulin sensitivity. METHODS:
      The study involved 118 individuals (mean age of 44+/-12 years; BMI=38.6+/-7.9
      kg/m(2)) without evidence of diabetes or cardiovascular disease. Insulin
      resistance was assessed by HOMA-IR index, which was used to stratify patients
      into tertiles. RESULTS: The mean HOMA-IR in tertile 1, the most insulin-sensitive
      group, was 2.7+/-0.8 and in tertile 3, the most insulin-resistant group, 9.1+/
      2.4 (P<0.001). Mean arterial pressure showed a linear and significant variation
      across the HOMA-IR tertiles 1, 2, and 3 (94.3+/-11.7; 98.7+/-11.4; 105.0+/-12.4
      mm Hg), as did fasting plasma glucose (93.6+/-12.1; 98.1+/-12.7; 100.0+/-11.0
      mg/dL), uric acid (4.7+/-1.4; 5.9+/-1.9; 6.3+/-1.4 mg/dL), HDL-cholesterol
      (48.1+/-11.6; 46.5+/-10.5; 42.2+/-8.0 mg/dL), and plasma adiponectin (7.8+/-3.3;
      7.0+/-2.8; 6.3+/-6.5 microg/mL), respectively. The results indicated that 27.5%
      of our patients had dysglicemia, 28.2% had hypertriglyceridemia, and 30.7% had
      arterial hypertension in the most insulin-sensitive tertile, when compared with
      51%, 53.8% and 79.4%, respectively, in the most insulin-resistant tertile. A
      stepwise regression analysis showed that only HOMA-IR and age independently
      affected the risk for increased systolic blood pressure. CONCLUSION: In
      conclusion, our findings have shown that the risk of developing essential
      hypertension, type 2 diabetes, and cardiovascular disease is accentuated in obese
      individuals who are also more insulin resistant.

PMID- 19393497
TI  - Implications of routinely measuring Ankle-Brachial Index (ABI) among patients
      attending at a Lipid Clinic.
AB  - BACKGROUND: Low (< or = 90) Ankle Brachial Index (ABI) values identify patients
      at high risk for cardiovascular (CV) disease and mortality. Implications for CV
      risk classification from routinely measuring ABI in the context of a Lipid Clinic
      have not been fully investigated. We aimed to evaluate whether and to what extent
      routine ABI determination on top of conventional risk prediction models may
      modify CV risk classification. METHODS: Consecutive asymptomatic non-diabetic
      individuals free from previous CV events attending for a first visit at a Lipid
      Clinic underwent routine ABI determination and conventional CV risk
      classification according either to national CUORE model (including age, gender,
      smoking, total and high density lipoprotein cholesterol, systolic blood pressure
      and current use of blood pressure lowering drugs) and SCORE model for low risk
      countries. RESULTS: In the overall sample (320 subjects, mean age 64.8 years) 77
      subjects (24.1%) were found to have low ABI value. Forty-two of 250 subjects
      (16.8%) and 47 of 215 individuals (21.3%) at low or moderate risk according to
      the CUORE and SCORE models, respectively, were found to have low ABI values, and
      should be reclassified at high risk. CONCLUSION: In a series of consecutive
      asymptomatic individuals in a Lipid Clinic, we observed a high prevalence of low
      ABI values among subjects deemed at low or moderate risk on conventional
      prediction models, leading to CV high-risk reclassification of roughly one fifth
      of patients. These findings reinforce recommendations for routine determination
      of ABI at least within referral primary prevention settings.

PMID- 19393498
TI  - The additive value of N-terminal pro-B-type natriuretic peptide testing at the
      emergency department in patients with acute dyspnoea.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) and its inactive counterpart NT
      proBNP can help to identify or rule out heart failure in patients presenting with
      acute dyspnoea. It is not well known whether measurement of these peptides can be
      omitted in certain patient groups. METHODS: We conducted a prospective
      observational study of 221 patients presenting with acute dyspnoea at the
      emergency department. The attending physicians estimated the probability of heart
      failure by clinical judgement. NT-proBNP was measured, but not reported. An
      independent panel made a final diagnosis of all available data including NT
      proBNP level and judged whether and how NT-proBNP would have altered patient
      management. RESULTS: NT-proBNP levels were highest in patients with heart
      failure, alone or in combination with pulmonary failure. Additive value of NT
      proBNP was present in 40 of 221 (18%) of the patients, and it mostly indicated
      that a more intensive treatment for heart failure would have been needed.
      Clinical judgement was an independent predictor of additive value of NT-proBNP
      with a maximum at a clinical probability of heart failure of 36%. CONCLUSION: NT
      proBNP measurement has additive value in a substantial number of patients
      presenting with acute dyspnoea, but can possibly be omitted in patients with a
      clinical probability of heart failure of >70%.

PMID- 19393499
TI  - Estimation of mortality savings due to a national program for diabetes care.
AB  - BACKGROUND: Diabetes-related complications can be reduced by better control of
      glycemia, lipid abnormalities and blood pressure. In recent years, efforts at
      improving diabetes care in Israel have been made. This study aims to estimate
      mortality savings related to a national program for diabetes care in Israel.
      METHODS: Total population data for Israel was projected to 2020. Current diabetes
      prevalence and disease management data were obtained from a national program of
      diabetes care. Projections of the program's effect were based on two models:
      improvement in glycemic control, reflected in Hb A1c levels, and improvement in
      overall diabetes care, reflected in the percentage with LDL<100 mg/dl, a proxy
      for multi-factorial control. Potential years of life lost (PYLL) and quality
      adjusted life years (QALYs) saved were calculated. RESULTS: A drop in average Hb
      A1c values from 8.13% at baseline to 7.36% in 2020 is expected, and as a result
      4216 deaths from diabetes will be prevented over the period 2001-2020, saving
      around 47,773 life years or 34,342 QALYs. Overall diabetes care, reflected in
      improving the control rate of LDL levels to <100 mg/dl from 36% in 2000 to 58% in
      2020, is estimated to prevent around 4803 deaths from diabetes over the period
      2001-2020., so the program will save around 47,127 PYLL or 32,862 QALYs.
      CONCLUSIONS: A nationwide program of diabetes care is estimated to result in
      significant reductions of overall, as well as CHD-related, mortality.

PMID- 19393500
TI  - Prediction clinical profile to distinguish between systolic and diastolic heart
      failure in hospitalized patients.
AB  - BACKGROUND: In recent decades, the growing incidence of patients with heart
      failure who have preserved systolic function, underlines the need to
      differentiate between heart failure due to diastolic dysfunction and that due to
      systolic dysfunction. OBJECTIVE: To develop a prediction profile of clinical
      parameters that enables clinicians to differentiate between patients with
      systolic and diastolic heart failure. METHODS: 164 patients admitted for
      congestive heart failure to the cardiology department of an academic tertiary
      care hospital, whose left ventricular systolic and diastolic function had been
      evaluated echocardiographically and who satisfied the Framingham criteria for
      heart failure, were prospectively recruited. All patients answered a
      questionnaire which included, in addition to other clinical variables, the
      Framingham criteria. RESULTS: Patients with diastolic heart failure (61.6%) were
      more likely to be older, female, and to present left ventricular hypertrophy
      (LVH), with a lower proportion of smokers, alcohol drinkers, coronary disease, q
      wave and left bundle branch block (all p<0.005). The predicting model obtained on
      the logistic regression analysis was very significant, with three variables and
      72.3% of correct predictions (x(2) value=40,457, p<0.001). These three variables,
      predictors of diastolic as opposed to systolic heart failure, were female sex
      (OR=3.546), left ventricle hypertrophy (OR=4.011) and absence of coronary disease
      (OR=3.547). CONCLUSION: Three variables which can be easily evaluated, female
      sex, left ventricular hypertrophy and presence or absence of coronary disease,
      may enable clinicians to differentiate between patients with systolic or
      diastolic heart failure.

PMID- 19393501
TI  - Fungal disease of the Western hemisphere: a patient with coccidioidomycosis.
AB  - We report the case of a 58 year old male patient with nonproductive coughing,
      fever, vomiting and loss of appetite, beginning at the moment that he returned
      back home from a 2 week holiday in California. His symptoms were accompanied by
      increased inflammatory markers in his blood (leucocytosis, high CRP) and
      pulmonary sequelae, becoming more prominent shortly after admission. Eventually,
      the final diagnosis of coccidioidomycosis was made by histopathology and
      confirmed by serology. Coccidioidomycosis is a rare infectious disease. However,
      the incidence in the endemic areas of this fungal infection is increasing and the
      population travelling towards its specific endemic regions in the United States
      and Southern America is considerably growing. Clinicians facing patients with
      pulmonary infection with the appropriate travel history and persistent pulmonary
      or systemic infection (with or without eosinophilia) should be alert to the
      possibility of coccidioidomycosis. Therefore, we present an up to date overview
      of the epidemiology, microbiology, clinical features, diagnosis and treatment of
      patients with coccidioidomycosis.

PMID- 19393502
TI  - A French national research project to the creation of an auscultation's school:
      the ASAP project.
AB  - Auscultation of pulmonary sounds provides valuable clinical information but has
      been regarded as a tool of low diagnostic value due to the inherent subjectivity
      in the evaluation of these sounds. This paper describes an ambitious study of in
      the so-called ASAP project or "Analyse de Sons Auscultatoires et Pathologiques".
      ASAP is a 3-year-long French collaborative project developed in the context of
      the News Technologies of Information and Communication. ASAP aims at making
      evolve the auscultation technics: by 1) the development objective tools for the
      analyse of auscultation sounds: electronic stethoscopes paired with computing
      device; 2) the creation of an auscultation sounds' database in order to compare
      and identify the acoustical and visual signatures of the pathologies; and 3) the
      capitalisation of these new auscultation techniques around the creation of a
      teaching unit: "Ecole de l'Auscultation". This auscultation's school will be
      destined to the initial and continuous formation of the medical attendants.

PMID- 19393503
TI  - Castleman-like reaction due to toxic substance ingestion.
AB  - Castleman disease (CD) is an uncommon lymphoproliferative disorder with a unique
      histopathology. Generally diagnosis is not difficult for an experienced
      pathologist. However, not usually, some histopathological entities or tissue
      reactions may mimic CD. Here CD-like reaction due to toxic substance ingestion
      has been presented.

PMID- 19393504
TI  - Localized scleroderma: a series of 52 patients.
AB  - BACKGROUND: Localized scleroderma also called morphea is a skin disorder of
      undetermined cause. The widely recognized Mayo Clinic Classification identifies 5
      main morphea types: plaque, generalized, bullous, linear and deep. Whether each
      of these distinct types has a particular clinical course or is associated with
      some patient-related features is still unclear. METHODS: We report here a
      retrospective series of patients with localized scleroderma with an attempt to
      identify features related to the type of lesion involved. The medical records of
      all patients with a diagnosis of localized scleroderma were reviewed by skilled
      practitioners. Lesions were classified according to the Mayo Clinic
      Classification. The relationship between each lesion type and various clinical
      features was tested by non-parametrical methods. RESULTS: The sample of 52
      patients included 43 females and 9 males. Median age at onset was 30 y (range 1
      76). Frequencies of patients according to morphea types were: plaque morphea 41
      (78.8%) (including morphea en plaque 30 (57.7%) and atrophoderma of Pasini
      Pierini 11 (21.1%)), linear scleroderma 14 (26.9%). Nine patients (17.3%) had
      both types of localized scleroderma. Median age at onset was lower in patients
      with linear scleroderma (8 y (range 3-44)) than in others (36 y (range 1-77))
      (p=0.0003). Head involvement was more common in patients with linear scleroderma
      (37.5%) than in other subtypes (11.1%) (p=0.05). Atrophoderma of Pasini-Pierini
      was never located at the head. Systemic symptoms, antinuclear antibodies and the
      rheumatic factor were not associated with localized scleroderma types or
      subtypes. CONCLUSION: These results suggest that morphea types, in adults are not
      associated with distinct patient features except for age at disease onset (lower)
      and the localization on the head (more frequent), in patients with lesions of the
      linear type.

PMID- 19393505
TI  - Magnetic compression biliary-enteric anastomosis for palliation of obstructive
      jaundice: initial clinical results.
AB  - PURPOSE: To report initial clinical experience with a nonsurgical method for
      sutureless biliary-enteric anastomosis with use of two magnetic elements that
      potentially overcomes the disadvantages of other palliative methods. MATERIALS
      AND METHODS: The technique involves percutaneous transhepatic insertion of one
      magnet into the bile duct under fluoroscopic guidance and insertion of a second
      magnet endoscopically into the duodenum. The adherence of the two magnets creates
      ischemic necrosis of bile duct and duodenal walls. When these tissues slough, the
      resulting hole allows enteric passage of the magnets and creates a biliary
      enteric fistula for decompression of an obstructed biliary system. A magnetic
      compression biliary-enteric anastomosis (MCBEA) was created in 34 patients (nine
      men; mean age, 64 years; age range, 46-82 y) with malignant obstructive jaundice
      at the level of the middle or distal common bile duct. RESULTS: There was no
      recurrent jaundice during the initial 30 postprocedural days. Total bilirubin
      levels decreased significantly in all patients 1 week after MCBEA formation (P <
      .0001), with normalization of bilirubin levels in eight of 34 patients. There was
      temporary occlusion caused by partial clogging of the bypass with coarse food in
      two cases, which was successfully revised endoscopically. Three patients required
      surgical revision as a result of tumor ingrowth. Median survival time was 10
      months. The cause of death in all patients was progression of underlying
      malignancy. CONCLUSIONS: Creation of a biliary-enteric anastomosis with magnetic
      compression is a feasible alternative for palliative treatment of obstructive
      jaundice with satisfactory results.

PMID- 19393506
TI  - The effect of hepatic radiofrequency ablation on stem cell trafficking in the rat
      model.
AB  - PURPOSE: To determine whether radiofrequency (RF) ablation causes increased
      hepatic embryonic stem cell trafficking in the rat liver model. MATERIALS AND
      METHODS: Right hepatic lobe RF ablation was performed in rats for 5 minutes at 15
      minutes (n = 2) and 48 hours (n = 2) before administration of rat hepatic
      embryonic stem cells (rhESCs). Green fluorescent protein-labeled rhESCs were
      injected intravenously, and all rats were killed 5 days after rhESC injection.
      Tissue was removed from RF ablation areas and untreated liver, the latter of
      which served as control. Slides were evaluated with fluorescent microscopy, and
      software fluorescence count was performed for evaluation of rhESC distribution.
      Regions of rhESC destination were divided into inner coagulation (zone A),
      periablational (zone B), and peripheral (zone C) zones. Fluorescence comparison
      was additionally performed between RF ablation areas and corresponding control
      tissues of the left hepatic lobe (segment II). Kruskal-Wallis testing was used
      for evaluations. RESULTS: Fluorescent pixel count was significantly higher in RF
      ablation areas than in respective controls: mean at 15 minutes, 10,471 +/- 3,830
      (SD) versus 1,889 +/- 1,427 (P < .05); mean at 48 hours, 15,177 +/- 7,091 versus
      2,868 +/- 1,714 (P < .05). High-power field samples showed significant
      distribution differences across zones: zone B, mean, 1,015.4 +/- 311; zone A,
      mean, 17.8 +/- 11; and zone C, mean, 141.2 +/- 51.4 (P < .05). CONCLUSIONS:
      RhESCs administered after RF ablation are trafficked to the periablational margin
      in significantly greater numbers than the remaining liver.

PMID- 19393507
TI  - Doxycycline sclerotherapy of an intraosseous femoral lymphatic malformation: case
      report and literature review.
AB  - Lymphatic malformations of the femur are rare benign conditions, with few
      published reports in the literature. Herein is presented an ambulatory 19-year
      old male subject with a painful lymphatic malformation of the distal femur
      characterized by a serpiginous intraosseous and extraosseous extent. Laboratory
      and physical examination were unremarkable except for a right knee joint effusion
      and patellar grind. The malformation was sclerosed twice with doxycycline,
      resulting in patient-reported decreased associated pain from an intensity of 9 of
      10 at presentation to 2 of 10 at 9-month follow-up.

PMID- 19393508
TI  - Brown syndrome--operate or observe?

PMID- 19393509
TI  - Bupivacaine injection of the lateral rectus muscle to treat esotropia.
AB  - PURPOSE: We report results of a pilot trial of bupivacaine injection into
      extraocular muscles as a method of enlarging and strengthening the muscles to
      treat strabismus. METHODS: Bupivacaine, in volumes from 1.0 to 4.5 mL and
      concentrations from 0.75% to 3.0%, was injected into 1 lateral rectus muscle in
      each of 6 patients with comitant esotropia with the use of the electrical
      activity recorded from the needle tip to guide injection. Magnetic resonance
      imaging was performed before and at intervals after injection to estimate changes
      in muscle size. Clinical measures of alignment were made before and at intervals
      after injection. Two patients required a second injection for adequate effect.
      RESULTS: Four patients showed improved eye alignment, averaging 12(Delta),
      measured an average of 367 days after the last injection (range, 244-540 days).
      Two patients were substantially unchanged. Alignment improvement for all 6
      patients averaged 8(Delta) (range, 0-14(Delta)). Volumetric enlargement of the
      injected muscle, computed from magnetic resonance images, was 6.2% (range, -1.5%
      to 13.3%). There was a positive correlation between alignment change and muscle
      enlargement averaging 0.65. Injection caused a retrobulbar hemorrhage in an
      unchanged patient that cleared without affecting vision. CONCLUSIONS: Bupivacaine
      injection improved eye alignment in 4 of 6 esotropic patients. There was a
      positive correlation between improved eye alignment and increased muscle size.
      Clinical and laboratory studies are underway to determine optimal dosages,
      effects in other strabismus conditions, and differential effects of bupivacaine
      on contractile and elastic muscle components.

PMID- 19393510
TI  - Brimonidine and apraclonidine as vasoconstrictors in adjustable strabismus
      surgery.
AB  - INTRODUCTION: Conjunctival and episcleral bleeding can interfere with
      visualization of anatomic structures during strabismus surgery. In the United
      Kingdom, dilute adrenaline (epinephrine) is routinely used to induce
      vasoconstriction at the beginning of strabismus surgery. Because it causes
      mydriasis and mildly inhibits accommodation, it is relatively contraindicated if
      early postoperative suture adjustment is planned. PURPOSE: To test whether
      topical alpha(2)-adrenergic agonists (brimonidine 0.2% and apraclonidine 1%) are
      useful alternatives to topical adrenaline (epinephrine) in adjustable suture
      strabismus surgery. METHODS: Prospective observational pilot study. Brimonidine
      0.2% or apraclonidine 1% was applied to the medial or lateral conjunctiva of 10
      consecutive adult patients undergoing strabismus surgery with adjustable sutures
      under general anesthesia. Video images were taken before and up to 20 minutes
      after instillation. The surface area of ocular surface blood vessels on the
      acquired images was quantified at selected intervals using imaging software.
      RESULTS: Both agents induced potent transient vasoconstriction of ocular surface
      vessels. Within 5 minutes of application, brimonidine reduces blood vessel
      surface area by 69.2% (95% CI, 50.4-88); this effect persists for 20 minutes.
      Apraclonidine reduces vessel area by 64.6% (95% CI, 57.2%-72%) within 10 minutes
      and begins to wear off over the following 10 minutes. CONCLUSIONS: Both
      brimonidine and apraclonidine may be useful alternatives to topical adrenaline
      (epinephrine) in adjustable suture strabismus surgery.

PMID- 19393511
TI  - Macular thickness, retinal thickness, and optic disk parameters in dominant
      compared with nondominant eyes.
AB  - PURPOSE: To determine whether differences exist in morphological structures of
      dominant and nondominant eyes in children ages 6 or 12 years. The following
      structural features were assessed: axial length, refraction, corneal radius of
      curvature, and retinal features-measured with the use of optical coherence
      tomography (OCT)-including macular and retinal nerve fiber layer thickness and
      optic disk parameters. METHODS: Of 4,118 children examined from 2003 to 2005 in
      the Sydney Myopia Study, 3,382 (82.1%) had OCT data for analysis. Comprehensive
      standardized eye examinations were performed, including best-corrected visual
      acuity. Ocular dominance was determined using the hole-in-card test, repeated on
      3 occasions. Dominance was assigned only if the 3 measurements were identical.
      "Fast" scans of the optic disk and retina were performed using OCT. RESULTS:
      Dominance was observed in 85% of subjects, with boys having a tendency toward
      right eye dominance. The dominant eye was longer (p = 0.001 and p = 0.0003 for 6-
      and 12-year-old patients, respectively) and more myopic (p = 0.002 and p =
      0.0001, respectively) than its counterpart. No retinal features consistently
      identified dominant from nondominant eyes in both age groups. CONCLUSIONS:
      Although dominant eyes tended to be longer and slightly more myopic than
      nondominant eyes, we found no consistent ocular structural differences between
      dominant and nondominant eyes with the use of OCT.

PMID- 19393512
TI  - Overcoming barriers to pediatric visual acuity screening through education plus
      provision of materials.
AB  - PURPOSE: The American Academy of Pediatrics (AAP) recommends that LEA and HOTV
      optotypes be used for vision screening and that adhesive tape be used to occlude
      one eye during testing. We have developed an educational program designed to
      improve the quality and efficiency of vision screening. The purpose of this study
      was to ascertain the effectiveness of this program. METHODS: All 672 pediatric
      doctors and nurses in the state of Alaska were surveyed by mail to assess their
      screening protocol and the number of patients cared for annually. Respondents
      received educational material, including an instructional video, eye patches for
      visual acuity testing, and a critical line HOTV test box. Subjects were
      resurveyed 3 months later to determine whether the instructional intervention
      altered their established protocol. RESULTS: Of the 672 practitioners contacted
      for the survey, 239 (35.6%) responded, representing 31,000 patients, or 62% of
      all preschool children in Alaska. Use of recommended optotypes was rare (Lea, 3%,
      HOTV, 7%) compared with the use of nonrecommended optotypes (including use of the
      E test by 40% of respondents). The postintervention survey was answered by 107
      (16%) practitioners. Of these, 24 (23%) reported that they had begun using an
      adhesive patch for visual acuity testing, whereas 19 (18%) had begun using AAP
      recommended testing optotypes. CONCLUSIONS: In-office video education and
      provided adhesive eye patches increased the use of patches in primary care
      preschool vision screening. Mail delivery was less effective than anticipated.

PMID- 19393513
TI  - Treatment of unilateral coronal synostosis by endoscopic strip craniectomy or
      fronto-orbital advancement: Ophthalmologic findings.
AB  - BACKGROUND: Unilateral coronal synostosis results in ipsilateral retrusion of the
      forehead and superior orbital rim, shortening the elevation of the orbital roof
      and contralateral frontal bossing and orbital roof depression. This
      craniosynostosis is associated with the development of V-pattern strabismus and
      aniso-astigmatism. Since 2004 endoscopic strip craniectomy performed in patients
      by 3 months of age has been offered as an alternative to fronto-orbital
      advancement at 9 to 11 months of age. We compare the incidence and severity of V
      pattern strabismus and aniso-astigmatism in children treated by these 2
      procedures. METHODS: A retrospective review identified 37 children with
      unilateral coronal synostosis treated with either fronto-orbital advancement or
      endoscopic strip craniectomy. Incidence and severity of V-pattern strabismus,
      fundus excyclotorsion, and aniso-astigmatism was recorded for an "early"
      examination (between 2 and 14 months of age) and a "late" examination (between 14
      and 45 months of age). RESULTS: Early examination revealed no statistical
      difference in severity of V-pattern strabismus or aniso-astigmatism between the 2
      groups. At late examination there was a trend toward greater severity of V
      pattern strabismus, an increase in excyclotorsion, and a statistically
      significant increase in the standard deviation of aniso-astigmatism in the cohort
      of children treated by fronto-orbital advancement. CONCLUSIONS: Children with
      unilateral coronal synostosis treated by early endoscopic strip craniectomy may
      develop less severe V-pattern strabismus, excyclotorsion, and range of aniso
      astigmatism than those treated by later fronto-orbital advancement. This is an
      early, retrospective, nonrandomized study with a short follow-up period; longer
      follow-up is necessary to confirm these results.

PMID- 19393514
TI  - Actinic conjunctivitis in children: Clinical features, relation to sun exposure,
      and proposed staging and treatment.
AB  - BACKGROUND: Actinic conjunctivitis is an ocular photosensitivity reaction found
      mainly in children in certain populations in the Andean regions of South America,
      Mexico, and in the southwestern United States. Its clinical features, treatment,
      and possible relation to duration of sun exposure have not been fully described
      in the ophthalmologic literature. METHODS: A 20-member ophthalmic team traveled
      to an Andean region of Ecuador to provide ophthalmic care to children. All
      children with conjunctivitis were examined. A novel 3-stage classification of
      actinic conjunctivitis, devised by one of the authors, was used to stage the
      disease. The parents of each child with actinic conjunctivitis were asked how
      much time the child spent outside. Histopathological evaluations were performed
      on children who underwent surgery. RESULTS: A total of 206 children were
      examined, of whom 36 had changes consistent with actinic conjunctivitis. Stage 1
      disease was diagnosed in 17 children, stage 2 in 9, and stage 3 in 10 in the most
      severely affected eye. The amount of time the child spent outside correlated with
      disease severity (r = 0.77, p < 0.001). Histopathologic samples showed an intense
      inflammatory response with hyperplasia of the vascular endothelium, pigmentary
      migration, and occasional eosinophilia. CONCLUSIONS: Actinic conjunctivitis is
      prevalent among children of the highlands of Ecuador. Although it has an allergic
      component, our data suggest that the severity of the disease is significantly
      associated with sun exposure. The finding that the lesions are found only in the
      exposed conjunctiva supports the hypothesis that UV exposure is the main cause of
      the disease.

PMID- 19393515
TI  - Age at the time of cataract surgery and relative risk for aphakic glaucoma in
      nontraumatic infantile cataract.
AB  - PURPOSE: To report the relative risk for aphakic glaucoma as a function of age at
      surgery in infants who underwent cataract surgery before 10 months of age for
      nontraumatic infantile cataract without microcornea. METHODS: This was an
      institutional retrospective case series (January 1985 to February 2003) of
      children who underwent cataract surgery without intraocular lens implantation for
      nontraumatic infantile cataract before 10 months of age. Patients with less than
      5 years' postsurgical follow-up, microcornea, persistent fetal vasculature,
      and/or other significant anterior segment abnormality were excluded. RESULTS: The
      surgical procedure in all cases was lens aspiration, posterior capsulotomy, and
      anterior vitrectomy with anterior small-incision techniques. Of 210 eyes (121
      patients), 55 eyes (26.2%; 31 patients [25.6%]) developed aphakic glaucoma.
      Relative risk for later aphakic glaucoma as a function of age at the time of
      surgery decreased from 1.85 (95% CI, 0.88-3.86) at 0-1 months of age to a nadir
      at 3-4 months of age (0.22 [95% CI, 0.05-0.96]) and then increased again to peak
      at 3.17 (95% CI, 1.1-9.11) at 5-6 months of age. CONCLUSIONS: The lowest relative
      risk for later aphakic glaucoma in our cohort was for surgery performed at 3-4
      months of age, for which the 95% CI remained less than 1.0. Further conclusions
      are limited by overlapping confidence intervals. However, because of amblyopia
      issues, we do not recommend delaying congenital cataract surgery beyond 4 weeks
      of life.

PMID- 19393516
TI  - Surgical intervention for traumatic cataracts in children: Epidemiology,
      complications, and outcomes.
AB  - PURPOSE: To describe the presentation, treatment, and outcomes of a series of
      patients with unilateral traumatic cataracts. METHODS: Retrospective,
      noncomparative review of 25 consecutive children with unilateral traumatic
      cataracts managed at a single institution during a 5-year period with regard to
      demographic data, mode of injury, clinical course, and outcome. RESULTS:
      Paintball and BB gun injuries were the most common mode of injury, accounting for
      28% of all cases, followed by injury from pens and pencils (16%). Preoperative
      visual acuity was poor in 19 patients (76%), and final postoperative visual
      acuity was poor (20/200 or worse) in 4 patients (16%); this difference was
      statistically significant (p < 0.001). Twenty-one percent of children with poor
      vision on initial examination had poor vision at their final examination, and no
      patients with vision better than 20/200 on initial examination developed poor
      vision postoperatively (p = 0.29). Patients who developed poor final vision were
      younger on average than those who achieved satisfactory vision (5.25 years vs 7.5
      years). Poor visual outcome did not appear to depend on the time from injury to
      presentation and time interval between injury and cataract extraction.
      CONCLUSIONS: Children with visually significant traumatic cataracts can have good
      outcomes if they are managed aggressively and appropriately. In our patient
      population, paintballs and BB guns accounted for more than 25% of traumatic
      cataract injuries, and a large number of traumatic cataracts were sustained by
      pens and pencils.

PMID- 19393517
TI  - Long-term visual outcome of penetrating keratoplasty in infants and children with
      Peters anomaly.
AB  - PURPOSE: To determine the long-term visual outcome of penetrating keratoplasty
      for Peters anomaly and to identify prognostic factors affecting final vision.
      METHODS: The records of children 12 years of age or younger who underwent
      penetrating keratoplasty for Peters anomaly between January 1, 1971 and December
      31, 1992 at Emory University were reviewed. Characteristics of the recipient,
      eye, donor, and surgical procedure were examined with the use of multivariate
      analyses. RESULTS: One hundred forty-four keratoplasties in 72 eyes of 47
      children who were followed for a minimum of 3 years from the date of first
      keratoplasty (median, 11.1 years) were reviewed. Visual acuities ranged from
      20/25 to no light perception. Twenty-nine percent of eyes achieved 20/400 or
      better visual acuities, whereas 38% had light perception or no light perception.
      Stromal vessels (p < 0.001) and larger donor corneas (p < 0.001) were independent
      predictors of poor outcome. Postoperative complications included graft failure (n
      = 44), cataract (n = 15), glaucoma (n = 14), retinal detachment (n = 16), and
      phthisis (n = 22). More than half of the eyes (n = 18) without graft failure,
      retinal detachment and/or phthisis saw 20/400 or better. CONCLUSIONS: Less than
      one-third of eyes with Peters anomaly undergoing keratoplasty achieved a visual
      acuity of 20/400 or better. Stromal vessels and large corneal grafts (>or=8 mm)
      were the only independent predictors of a poor visual outcome.

PMID- 19393518
TI  - Tortuosity of arterioles and venules in quantifying plus disease.
AB  - BACKGROUND: Plus disease is the major criterion for laser treatment of
      retinopathy of prematurity. ROPtool is a computer program that traces retinal
      blood vessels and measures their tortuosity. Our objectives were to determine (1)
      whether examiners could accurately discriminate between arterioles and venules
      and (2) whether tortuosity sufficient for plus disease and pre-plus disease was
      assessed most accurately by considering arterioles, venules, or both. METHODS:
      One hundred retinal vessels were identified in 25 images randomly selected from
      184 total images. Three pediatric ophthalmologists independently designated
      vessels as arteriole or venule. Seventy-seven images that had at least 1
      traceable arteriole and venule in each quadrant were analyzed by ROPtool, and the
      results were compared with the consensus of 3 expert examiners. Receiver
      operating characteristics (ROC) curves were generated and areas under the curves
      calculated to quantify the diagnostic utility of ROPtool's assessment of
      tortuosity of arterioles, venules, and both. RESULTS: Three pediatric
      ophthalmologists agreed on the designation of arteriole or venule for 83 of 100
      blood vessels. With the use of expert consensus as the reference standard, areas
      under the ROC curves for identification of tortuosity sufficient for plus disease
      were 0.91, 0.70, and 0.93 for arterioles, venules, and both, respectively. Areas
      under the ROC curves for identification of tortuosity sufficient for pre-plus
      disease were 0.91, 0.63, and 0.90 for arterioles, venules, and both,
      respectively. CONCLUSIONS: When considering whether tortuosity is sufficient for
      plus or pre-plus disease, the assessment of either arterioles alone or of
      arterioles and venules together resulted in high diagnostic accuracy.

PMID- 19393519
TI  - Cost-utility analysis of screening and laser treatment of retinopathy of
      prematurity.
AB  - PURPOSE: Retinopathy of prematurity (ROP) is a major cause of lifelong blindness
      beginning in infancy. Utility analysis is used to describe the effect of illness
      and medical intervention on an individual's quality of life during the course of
      a lifetime. In this study, cost-utility analysis is used to evaluate the cost
      effectiveness of both screening and laser photoablation for ROP. METHODS: Data
      from 2 neonatal intensive care units were recorded for infants screened and
      treated for ROP between March 4, 2004, and January 5, 2006. The cost model was
      developed using procedures classified by Current Procedural Terminology and the
      costs paid for by the Centers for Medicare and Medicaid Services for 2006. Visual
      acuities were obtained from 10-year post-laser data and from the 10-year post
      CRYO-ROP untreated cohort. RESULTS: During the study period, 515 infants received
      screening and treatment for ROP. They required a mean 3.4 exams per infant; 11.2%
      received laser photoablation. Mean visual acuities were 0.5 (Snellen 20/40) for
      laser-treated eyes and 0.20 (Snellen 20/100) for those who did not receive
      treatment. The cost-effectiveness of screening and laser photoablation of ROP in
      2006 is $650/quality-adjusted life years. When discounted 3% per year for the
      time value of money, the cost is $1,565/ quality-adjusted life years.
      CONCLUSIONS: The screening and laser photoablation of ROP continue to be
      extremely cost-effective medical interventions.

PMID- 19393520
TI  - Abnormal extraocular muscle anatomy in a case of Williams-Beuren Syndrome.
AB  - We report the case of young boy with Williams-Beuren syndrome with abnormal
      extraocular muscle insertions that were discovered during routine strabismus
      surgery. All 4 horizontal rectus muscles were thin, and 3 inserted much further
      back from the limbus than normal.

PMID- 19393521
TI  - Pseudotumor cerebri associated with lithium use in an 11-year-old boy.
AB  - Pseudotumor cerebri, also termed idiopathic intracranial hypertension, is defined
      by increased intracranial pressure in the setting of normal brain imaging and
      cerebrospinal fluid analysis. It can often be associated with optic nerve head
      edema. Several medications have been associated with pseudotumor cerebri,(1)
      including the use of lithium carbonate in the adult population(3) as well as in
      adolescents.(4) Signs and symptoms of increased intracranial pressure typically
      resolve after cessation of lithium carbonate usage.(5) We report a case of the
      onset of pseudotumor cerebri associated with lithium treatment in a child who
      sustained long-term optic atrophy and vision loss and required acetazolamide
      treatment for approximately 1 year after cessation of lithium.

PMID- 19393522
TI  - Lymphocytic infundibulo-neurohypophysitis: An unusual cause of recurrent optic
      neuropathy in a child.
AB  - Lymphocytic infundibulo-neurohypophysitis (LINH), a rare autoimmune disease, is
      distinct from lymphocytic hypophysitis and is characterized by lymphocytic and
      plasma cell infiltration of the posterior lobe of the pituitary and the pituitary
      stalk.(1) We report the case of a young boy who presented with recurrent, steroid
      responsive optic nerve dysfunction and diabetes insipidus. T1-weighted magnetic
      resonance imaging scans of the brain showed an isointense soft tissue mass within
      the sella turcica and a thickened pituitary stalk. Tissue specimen resected at
      transsphenoidal surgery revealed chronic inflammation with infiltration of
      lymphocytes and no granulomatosis or necrosis, establishing the diagnosis of
      LINH.(2) This is the first report of optic neuropathy in association with LINH in
      a child.

PMID- 19393524
TI  - Ocular abnormalities in Floating-Harbor syndrome.
AB  - We present the first case report of a comprehensive eye examination in a patient
      with Floating-Harbor syndrome. Ocular findings were limited to partially
      accommodative, acquired esotropia, and unusual eyelashes. A variety of other
      ocular features have been previously reported in the nonophthalmic medical
      literature and are herein reviewed.

PMID- 19393523
TI  - Genetic and clinical evaluation of juvenile retinoschisis.
AB  - Juvenile retinoschisis is a rare retinal dystrophy caused by RS1 gene
      mutations.(1) Clinical examinations and molecular testing definitively diagnosed
      juvenile retinoschisis in 2 male infants, one of whom had a novel mutation not
      previously reported in the United States. Genetic testing may be the simplest way
      to confirm this diagnosis in infants.

PMID- 19393525
TI  - Occlusion properties of prosthetic contact lenses for the treatment of amblyopia.

PMID- 19393526
TI  - Myiasis of the upper eyelid (Jaapos 2008;12:516-17).

PMID- 19393531
TI  - [Oncologic and functional outcomes after radical prostatectomy in T3 prostate
      cancer].
AB  - According to current literature, the gold standard treatment for T3 prostate
      cancer is the combination of radiotherapy and extended hormonotherapy. Clinical
      staging based on digital rectal examination seems useless nowadays, since 20% of
      T3 prostate cancer is overevaluated during physical examination. Prostatic MRI is
      extensively needed to evaluate extraprostatic extension during preoperative work
      up. EAU guidelines recommend radical prostatecomy only in selected patients: less
      than or equal to cT3a, PSA less than 20 ng/ml and biopsy Gleason score less than
      or equal to 8. Carcinologic control obtained after radical prostatectomy is
      variable from one series to another, with biochemical free survival rate at 5, 10
      and 15 years that range from 45 to 62%, 43 to 51%, and 38 to 49%. Specific
      survival rates at 5, 10 and 15 years are, respectively, of 84 to 98%, 85 to 91%
      and 76 to 84%. Surgical margins rate differ from 22 up to 61% corresponding to
      several operative techniques and surgeon's own experience. Regarding urinary
      continence, functional outcomes are in line with those of prostatectomy for
      localized prostate cancer. Considering erectile dysfunction, rates are linked
      with the type of surgery, which can be extensive or not. There is no impact on
      overall or specific survival of neoadjuvant treatments. One current question
      remains the efficacy of early adjuvant treatment after prostatectomy, especially
      adjuvant irradiation. Radical prostatectomy can be considered in selected cases
      as a viable alternative first-line treatment option. However, patients have to be
      warned that they may undergo complementary treatments during the postoperative
      course of the disease.

PMID- 19393532
TI  - [Why and how to explore erectile function in patient with cardiovascular risk?].
AB  - Erectile dysfunction (ED) is a frequent disorder, which can be the first symptom
      of an underlying pathology such as cardiovascular diseases. Doctors should have a
      good understanding of erectile dysfunction and must be aware of the importance of
      detecting and investigating any erectile disorders. Detection of an erectile
      dysfunction induces to search underlying cardiovascular diseases, but also
      urinary symptoms, hormonal deprivation, mood and relational alterations and
      iatrogenous complications. Determination of erectile disorders therefore
      represents an excellent opportunity to conduct a work-up of this symptom, as an
      integral part of health policy.

PMID- 19393533
TI  - [Radiotherapy in prostate cancer: data from ASTRO 2008].
AB  - The annual convention of the American Society for Therapeutic Radiology and
      Oncology (ASTRO) took place in Boston, MA, 21-25 September 2008. On the occasion
      of this meeting, in which the past year's main advances in radiation oncology
      have been highlighted, results from clinical studies that may significantly
      impact the standard clinical practice were presented, particularly in the fields
      of locally advanced prostate cancer treated with non surgical approaches, and pT3
      and/or R1 prostate cancer managed with radical prostatectomy. Randomized studies
      that emphasize the role of dose escalation have been updated.

PMID- 19393534
TI  - [Preoperative factors of misdiagnosis of renal angiomyolipoma].
AB  - OBJECTIVES: To explain the high incidence of misdiagnosis of angiomyolipoma (AML)
      prior to surgery. MATERIALS AND METHODS: Between 1989 and 2007, 2,657 patients
      were operated for a renal tumor at Dupuytren hospital in Limoges and at Cochin
      hospital in Paris. In 85 cases (3.2%), tumors were AMLs on pathology. The group
      of patients in which the diagnosis was done preoperatively was compared to the
      one in which the diagnosis was missed. RESULTS: Mean age of patients was 57-years
      old and the sex-ratio was five women for one man. The mean size of AMLs was 5.4
      cm. The patients were symptomatic in 46% of cases (39/85). The diagnosis of AML
      was ignored preoperatively in 62 patients (73%). In multivariate analysis, the
      small size of the AML, low proportion of fat and male sex were significantly
      associated with misdiagnosis of AML (p<0.001, p<0.018 and p<0.008, respectively).
      CONCLUSIONS: The incidence of misdiagnosis of AML preoperatively is high. The
      diagnosis seems particularly difficult when the tumor is small or contains a
      small proportion of fat. In addition, this study highlights that the diagnosis of
      AML is frequently ignored in men. The increased resolution of CTscan and the use
      of preoperative biopsies for tumors less than 4 cm could be helpful to decrease
      the incidence of useless surgery of AMLs.

PMID- 19393535
TI  - [The viability of kidneys tested by gadolinium-perfusion MRI during ex vivo
      perfusion].
AB  - INTRODUCTION: Marginal kidneys must be reanimated before their transplantation.
      Reanimation is conducted with hypothermic pulsatile perfusion. The tests used
      generally to demonstrate the viability is the vascular resistance which is not
      convenient for everybody. We have developed a magnetic resonance compatible
      perfusional technology allowing us to test the organs during the perfusion by Gd
      perfusion MRI. METHODS AND RESULTS: We have used pigs' kidneys with no warm
      ischemic time to establish the basis in a normal kidney. After an eight-hour
      hypothermic pulsatile perfusion, kidneys are submitted to a Gd perfusion. First,
      we measure the anatomy of the vessels, then the distribution of Gd in the kidney.
      We obtain simultaneously a dynamic study of the organs where T0 represents the Gd
      bolus arrival in the cortex and TP the maximum saturation time of Gd. CONCLUSION:
      We have observed that a normal T0 is inferior to 30s and TP is inferior to one
      minute. We have compared these values with ATP resynthesis in these organs and
      found that they correlate. We hope for the future through that predictive use of
      Gd-MRI to avoid the clinical use of "too" marginal kidneys or the discard of good
      kidneys but not corresponding with the vascular resistance theory.

PMID- 19393536
TI  - [Circumstances of prescription of hormone therapy for patients with prostate
      cancer].
AB  - AIMS: Although screening has improved the diagnosis of prostate cancer, hormone
      therapy still plays an important role in its treatment. This article aims to
      evaluate the circumstances for the use of hormone therapy in 2007. MATERIAL:
      Observational study, with no intervention, carried out between October 2006 and
      March 2007, on 208 urologists and radiotherapists. This study allowed for the
      analysis of the circumstances and reasons for the prescription of hormone therapy
      for four to eight consecutive patients. RESULTS: The 1187 patients included had
      an average age of 73.5+/-8 years (median: 75 years). The cancer had been
      diagnosed for 1.1+/-2.3 years. The diagnosis had generally been made at localized
      stage, less often at local advanced stage (37.2%, n=442) or metastasis (15.4%,
      n=183). The prescription of GnRH analogues was principally motivated by a
      biological recurrence (22.2%, n=263), the presence of bone or visceral metastasis
      at time of diagnosis (22.1%, n=262) or a contraindication of local treatment at
      localized stage (16.6%). The decision to use hormone therapy was taken jointly by
      the doctor and the patient in 57% of cases. The majority of patients (92%)
      benefited from an injection every three months. CONCLUSION: Hormone therapy by
      GnRH analogues remains established for cases of cancer metastasis or in cases of
      recurrence. This observation corroborates scientific recommendations regarding
      the use of GnRH analogues.

PMID- 19393537
TI  - [Percentage of positive biopsy cores at the onset of hormone therapy for prostate
      cancer: prognostic significance].
AB  - INTRODUCTION: We hypothesized that it would predict time to hormonal independence
      and survival in prostate cancer patients treated by androgen deprivation therapy
      (ADT). MATERIAL AND METHODS: We used clinical data from 403 men treated with ADT
      between 1980 and 1999 and focused on a subgroup of 220 patients treated with GnRH
      analogue. Percentage PBC was defined as the number of positive biopsy cores
      multiplied by 100 and divided by the total number of biopsy cores. RESULTS:
      Median percentage PBC was 83.3% (16.7-100%). Mean follow-up was 57.4 months.
      Survival at 5 years in men with 83.3% PBC or less was 62.3, 89.1 and 82.6% for
      recurrence-free, specific and overall survival respectively, significantly better
      than that of men with a percentage PBC of more than 83.3% (32.2, 74.7 and 67.7%,
      respectively; p<0.004). Among the factors available in the pretreatment setting,
      namely age, clinical stage, PSA, Gleason score, bone scan and percentage PBC, the
      latter was independently associated with survival in multivariate analysis.
      CONCLUSIONS: Percentage PBC may improve the ability to predict time to hormonal
      resistance and survival in patients treated with ADT for prostate cancer. This
      finding warrants further investigation.

PMID- 19393538
TI  - [Treatment of benign prostatic hyperplasia by radiofrequency (TUNA): a
      monocentric study of 28 cases treated in ambulatory surgery].
AB  - AIM: To assess the feasibility of ambulatory surgery in the treatment of benign
      prostatic hyperplasia using radio frequency (TUNA) and evaluate its place in
      terms of efficiency among other minimally invasive surgical techniques. METHOD:
      Fifty-four patients suffering from benign prostatic hyperplasia and for whom
      medical treatment was ineffective, were treated with radio frequency between
      September 2004 and June 2007. Among them, 28 patients, whose average age was 65.8
      (aged 52-82), were selected for Transurethral Needle Ablation (TUNA) as
      outpatients. Urine status was assessed before and after TUNA treatment using the
      International Prostate Score System, the Quality Of Life-score to urinary
      symptoms, the measures of the maximal flow rate and of the residual urine. The
      erectile function was assessed using the five-item version of the International
      Index of Erectile Function (IIEF-5). RESULTS: With an average regression of 12.14
      months, a significant improvement in urine status was observed with an average
      IPSS score passing from 22.4 to 9.75 and an average quality of life score passing
      from 4.9 to 1.9. The maximum flow rate and average flow volume increased
      significantly from 8.66 to 14.6 ml/s and from 202 to 248.4 ml respectively.
      Average urine residue was reduced from 177.4 to 112.2 ml (p<0.05). The IIEF-5
      score did not increase significantly (14.1 versus 12.8). There were no cases of
      patients being rehospitalised. One case of prostatitis and six cases of acute
      urinary retention were observed at the postoperative stage. The rate of retreat
      was 21.4%. CONCLUSION: TUNA treatment is a minimally invasive technique of benign
      prostatic hyperplasia which can be carried out in ambulatory surgery and which is
      effective for urinary symptoms with little risk of morbidity. It is an
      alternative to medical treatment and does not replace planned surgical treatment.

PMID- 19393539
TI  - [Impact of nocturia on sleep efficiency in patients with benign prostatic
      hypertrophy].
AB  - OBJECTIVE: To assess sleep efficiency in patients presenting with nocturia and
      symptomatic benign prostatic hypertrophy (BPH). MATERIAL AND METHODS: This
      prospective observational survey was carried out in France by 113 urologists. A
      total of 1376 patients (mean+/-SD age: 68.8+/-9.0 years) consulting for BPH with
      greater than two nocturia episodes per 24 hours were assessed with a mean I-PSS
      score of 15.5+/-6.4 (symptoms greater than 19 [severe] in 26.9% of cases).
      Patients used a sleep diary to record the previous night's total; sleep
      efficiency is expressed as percentage ratio, representing the total amount of
      actual sleep between initial sleep onset and final awakening. Sleep disorders
      were assessed using HD-43 questionnaire based on International classification of
      sleep disorders. RESULTS: 29.2% of the patients suffered from chronic insomnia,
      considered as primary insomnia (in 29.5% of cases) or related to either BPH
      (63.0%); snoring/sleep apnoea in 12.5% of cases. The mean sleep efficiency index
      was 87.2+/-13.7% and appeared to be significantly lower in BPH-related insomnia.
      Significantly lower sleep efficiency index values were observed as the severity
      (I-PSS score) of the BPH symptoms increased (89.5+/-12.1% for mildly symptomatic
      BPH vs. 84.0+/-15.6% for severely symptomatic BPH, P<0.001). Sleep efficiency
      index lowered with nocturia frequency (89.8+/-11.3% for two nocturia episodes vs.
      80.4+/-17.3% for five nocturia episodes or more, P<0.001) and chronic insomnia
      frequency increased with nocturia frequency (21.4% for two nocturia episodes vs.
      45.2% for five nocturia episodes or more, P<0.001). CONCLUSIONS: Insomnia is
      frequent in patients presenting with BPH-related lower urinary tract symptoms
      (LUTS) and is mainly secondary to these LUTS. There is a significant correlation
      between the frequency of nocturia and the severity of insomnia.

PMID- 19393540
TI  - [Demography of residents in urology in France: appraisal and perspectives].
AB  - PURPOSE: The objective was to identify the number of residents registered in the
      course of urology in France in 2008, and to make a forecast in the number of
      posts of fellow and specialist assistant available at the end of their course.
      MATERIAL: From January to February 2008, a questionnaire identified in all French
      University Hospital the number of residents enrolled in the urology course, and
      the number of posts of fellow and specialist assistant in urology in the region.
      The year of the end of the course has been determined for each resident in
      compliance with seniority, and taking into account the availability. The number
      of fellow and specialist assistant posts available in the same period was
      estimated by considering the duration of each postinternship, and any change in
      the number of posts. RESULTS: Our census counted 207 residents, 76 fellow posts,
      10 specialist assistant posts. Of the 207 residents, 29 completed their studies
      in 2008, 57 in 2009, 60 in 2010, 61 in 2011. Following our methodology, there was
      a lack of fellow and specialist assistant posts available from November 2010 (-15
      posts in 2010, -7 posts in 2011). CONCLUSION: Our study showed an increase in the
      number of residents enrolled in urology course by years of promotion, causing a
      lack of fellow and specialist assistant posts from 2010. Apart from an opening of
      additional fellows and specialist assistants at that time, our study highlights
      the long-term regulation of entries in the urology course ensuring a
      postinternship quality.

PMID- 19393541
TI  - [Renal metastasis of an esophagus epidermoid carcinoma].
AB  - Renal metastases in the evolution of an esophagus epidermoid carcinoma are rare
      and are frequently bilateral or associated with many other metastases. The
      authors present an original article of a single metastasis. They discuss the
      importance of imagery and locoregional status in the management of patient.

PMID- 19393542
TI  - [Varicocele thrombosis: a rare etiology of testicular pain].
AB  - Acute testicular pain is frequent in urology. If torsion of the spermatic cord
      and orchiepididymitis are usual, varicocele thrombosis is an unusual clinical
      entity we reported.

PMID- 19393543
TI  - [Iatrogenic paratesticular fibrous pseudotumor].
AB  - Authors report a case of probably iatrogenic paratesticular fibrous pseudotumor.
      A 33-year-old man presented with a history of increased scrotal volume after
      laborious urethral catheterism. Ultrasound scanning first suggested testicular
      malignant lesion. Surgical findings showed thick and fibrous scrotal wall
      surrounding a pseudocystic cavity which contained urine coming from a bulbar
      urethral rupture. Testicles were normal. Urethral suture and total excision of
      the scrotal mass were performed. Diagnosis was histologically corrected.
      Diagnosis and management are discussed with a review of the literature.

PMID- 19393544
TI  - Lantibiotics: diverse activities and unique modes of action.
AB  - Lantibiotics are one of the most promising alternative candidates for future
      antibiotics that maintain their antibacterial efficacy through many mechanisms.
      Of these mechanisms, some modes of activity have recently been reported,
      providing opportunities to show these peptides as potential candidates for
      forthcoming applications. Many findings providing new insight into the detailed
      molecular activities of numerous lantibiotics are constantly being uncovered. The
      combination of antibiotic mechanisms in one lantibiotic molecule shows its
      diverse antimicrobial usefulness as a future generation of antibiotic. Since
      lantibiotics do not have any known candidate resistance mechanisms, the
      discovered distinct modes of activity may revolutionize the design of anti
      infective drugs through the knowledge provided by these super molecules. In this
      review, we discuss the rising assortment of lantibiotics, with special emphasis
      on their structure-function relationships, addressing the unique activities
      involved in their individual modes of action.

PMID- 19393545
TI  - Simultaneous non-thermal saccharification of cassava pulp by multi-enzyme
      activity and ethanol fermentation by Candida tropicalis.
AB  - Cassava pulp, a solid by-product from starch processing, is a promising and
      underused biomass that can be converted to biofuels and other value-added bio
      products. In this study, an alternative cassava pulp saccharification process,
      which utilizes the multi-activity enzyme from Aspergillus niger BCC17849 and
      obviates the need for a pre-gelatinization step, was developed. The crude multi
      enzyme composed of non-starch polysaccharide hydrolyzing enzyme activities,
      including cellulase, pectinase and hemicellulase act cooperatively to release the
      trapped starch granules from the fibrous cell wall structure for subsequent
      saccharification by raw starch degrading activity. A high yield of fermentable
      sugars, equivalent to 716 mg glucose and 67 mg xylose/g of cassava pulp, was
      obtained after 48 h incubation at 40 degrees C and pH 5 using the multi-enzyme,
      which was greater than the yield obtained from the optimized combinations of the
      corresponding commercial enzymes. The multi-enzyme saccharification reaction can
      be performed simultaneously with the ethanol fermentation process using a
      thermotolerant yeast Candida tropicalis BCC7755. The combined process produced
      14.3 g/l ethanol from 4% (w/v) cassava pulp after 30 h of fermentation. The
      productivity rate of 0.48 g/l/h is equivalent to 93.7% of the theoretical yield
      based on total starch and cellulose, or 85.4% based on total fermentable sugars.
      The non-thermal enzymatic saccharification process described is more energy
      efficient and yields more fermentable sugar than the conventional enzymatic
      process. Furthermore, the process is applicable for production of various bio
      products of economic importance.

PMID- 19393546
TI  - Production of beta-xylanase by a Thermomyces lanuginosus MC 134 mutant on corn
      cobs and its application in biobleaching of bagasse pulp.
AB  - The production of hemicellulases by Thermomyces lanuginosus SK using oatspelts
      xylan was examined during submerged cultivation. A high level of extracellular
      xylanase (346+/-10 U ml(-1)) production was observed on the fifth day; however,
      accessory enzyme levels were low. T. lanuginosus SK was further subjected to UV
      and N-methyl-N-nitro-N-nitrosoguanidine mutagenesis. The T. lanuginosus MC 134
      mutant showed a 1.5 fold increase in xylanase production on oatspelts xylan,
      compared to the wild type strain. Xylanase production was further enhanced to
      3299+/-95 U ml(-1) by using corn cobs under optimized growth conditions. A
      reduction in xylanase production was observed in a 5 L fermenter. Also, the
      biobleaching efficiency of crude xylanase was evaluated on bagasse pulp, and a
      brightness of 46.07+/-0.05% was observed with the use of 50 U of crude xylanase
      per gram of pulp. This brightness was 3.6 points higher than that of the
      untreated samples. Reducing sugars (25.78+/-0.14 mg g(-1)) and UV-absorbing
      lignin-derived compound values were considerably higher in xylanase-treated
      samples. T. lanuginosus MC 134 has a potential application in the pulp and paper
      industries.

PMID- 19393548
TI  - Microbial production of xylitol from L-arabinose by metabolically engineered
      Escherichia coli.
AB  - An Escherichia coli strain, ZUC99(pATX210), which can produce xylitol from L
      arabinose at a high yield, has been created by introducing a new bioconversion
      pathway into the cells. This pathway consists of three enzymes: L-arabinose
      isomerase (which converts L-arabinose to L-ribulose), D-psicose 3-epimerase
      (which converts L-ribulose to L-xylulose), and L-xylulose reductase (which
      converts L-xylulose to xylitol). The genes encoding these enzymes were cloned
      behind the araBAD promoter in tandem so that they were polycistronically
      transcribed from the single promoter, like an operon. Expression of the
      recombinant enzymes in the active form was successfully achieved in the presence
      of L-arabinose. A xylitol production profile of the recombinant strain was
      evaluated by shake-flask fermentation. ZUC99(pATX210) produced 2.6 g/l xylitol
      using 4.2 g/l L-arabinose with a xylitol yield of 0.62 g/g L-arabinose in 36 h.
      It was determined that utilization of glycerol as a co-substrate significantly
      improved xylitol production and yield. In the presence of 11.8 g/l glycerol,
      ZUC99(pATX210) produced 9.7 g/l xylitol from 10.5 g/l L-arabinose with a xylitol
      yield of 0.92 g/g L-arabinose in 36 h. ZUC99(pATX210) also exhibited efficient
      conversion in fermentor experiments with 1 l medium containing L-arabinose and
      glycerol. The strain produced 14.5 g/l xylitol from 15.2 g/l L-arabinose with a
      xylitol yield of 0.95 g/g L-arabinose in 30 h.

PMID- 19393547
TI  - Trehalose-6-phosphate synthase 1 from Metarhizium anisopliae: clone, expression
      and properties of the recombinant.
AB  - Trehalose, an important component in fungal spores, is a disaccharide which
      protects against several environmental stresses, such as heat, desiccation, salt.
      Trehalose-6-phosphate synthase 1 (TPS1) is a subunit of trehalose synthase
      complex in fungi; it plays a key role in the biosynthesis of trehalose. In this
      study, a full-length cDNA from Metarhizium anisopliae encoding TPS1 (designated
      as MaTPS1) was isolated. The MaTPS1 cDNA is composed of 1836 nucleotides encoding
      a protein of 517 amino acids with a molecular mass of 58 kDa. The amino acid
      sequence has a relatively high homology with the TPS1s in several other
      filamentous fungi. Southern blot analysis showed that MaTPS1 gene occurs as a
      single copy in the M. anisopliae genome. And MaTPS1 was cloned into Pichia
      pastoris KM71 and secretively expressed with a histamine tag to facilitate a
      rapid purification of recombinant MaTPS1 (designated reTPS1). The properties of
      reTPS1 were examined. The K(m) value of reTPS1 for UDP-glucose and glucose-6
      phosphate was 9.6 mM and 3.9 mM, respectively, and the optimal pH and temperature
      were about 6.5 and 40 degrees C. The enzyme was highly specific to glucose-6
      phosphate for glucosyl acceptor, and its activity decreased rapidly as the
      concentrations of phosphate increased. The expression system will provide
      sufficient amounts of reTPS1 for future structural characterization of the
      protein and use for further investigation of MaTPS1's function.

PMID- 19393549
TI  - Investigation of inclusion body formation in recombinant Escherichia coli with a
      bioimaging system.
AB  - A bioimaging system using giant protoplasts of recombinant Escherichia coli was
      developed for examining conditions affecting the formation of inclusion bodies.
      After the giant protoplasts were prepared, isopropyl-beta-d-thiogalactopyranoside
      (IPTG) was used to induce expression of the blue fluorescence protein (BFP) gene.
      Fluorescence microscopy revealed that two types of fluorescence were emitted; one
      by soluble BFP and the other by aggregated BFP. As a result, the parameters that
      influence the formation of inclusion bodies can be examined by observing the
      fluorescence emitted by BFP, in real-time, with a fluorescence microscope. It was
      found that the aggregated BFP decreased with decreasing cultivation temperature,
      and the formation of inclusion bodies increased with decreased pH and increased
      IPTG concentrations. In addition, the aggregated form of BFP emitted
      fluorescence, indicating that BFP inclusion bodies might remain, at least
      partially, in a properly folded native-like form.

PMID- 19393550
TI  - Overexpression of MSN2 in a sake yeast strain promotes ethanol tolerance and
      increases ethanol production in sake brewing.
AB  - To improve the ethanol tolerance of sake yeast we constructed a sake yeast strain
      that overexpresses MSN2, a transcription factor that is activated by several
      environmental stresses, including ethanol. We showed that this strain is more
      ethanol tolerant and produced more ethanol in a sake mash than a control strain.

PMID- 19393551
TI  - Effect of salt concentration in anammox treatment using non woven biomass
      carrier.
AB  - Effect of high salt concentration on the anammox treatment was investigated to
      establish an acclimation strategy under high salt concentration conditions. An
      anammox fixed-bed reactor with non-woven biomass carrier was used and the salt
      concentration was gradually increased from 2.5 g L(-1) to 33 g L(-1). The anammox
      reactor demonstrated stable nitrogen removal rate (NRR) of 1.7 kg-N m(-3) d(-1)
      for 65 days under a salt concentration of 30 g L(-1). However, the NRR sharply
      declined at a salt concentration of greater than 30 g L(-1). The bacterial
      community was examined by 16S rRNA gene analysis and DGGE after the acclimation
      of the anammox sludge to high salt conditions. Although the salt concentration
      was almost sea level, the freshwater anammox bacteria, KU2, were detected. In
      addition, the unidentified bacteria which perhaps belong to candidate division
      OP10 and Lysobacter sp. were found to coexist with anammox bacteria at a salt
      concentration of 30 g L(-1).

PMID- 19393552
TI  - A high-yield and scaleable adenovirus vector production process based on high
      density perfusion culture of HEK 293 cells as suspended aggregates.
AB  - Cells of the human embryonic kidney cell line (HEK 293) were grown as suspended
      aggregates in stirred vessels and infected with a recombinant adenovirus vector
      (Ad-TH-GFP). Regular spherical aggregates with the mean diameter less than 300
      microm and a viable cell density greater than 5 x 10(6) cells x ml(-1) were
      readily achieved after 9 day culture in spinner flasks. The HEK 293 cells growing
      as suspended aggregates could be efficiently infected by Ad-TH-GFP at an MOI of
      10 with a prolonging infection time up to 144 hour post-infection (hpi). The time
      profile of Ad-TH-GFP production was strongly corresponding to the infection
      process with a virus concentration peak occurred consistently at 144 h after
      infection. And the infected aggregates essentially maintained spherical in shape,
      the portion of dissociated cells from the infected aggregates was less than 5% at
      144 hpi. Perfusion culture of HEK 293 cells grown as suspended aggregates in a
      7.5 L stirred tank bioreactor and infected with Ad-TH-GFP at a density higher
      than 1 x 10(7) cells x ml(-1) resulted in a similar Ad-TH-GFP production
      kinetics, but a much higher virus yield approximately at 5.7 x 10(11) GTU ml(-1)
      at 144 hpi to that of the infected spinner flask cultures. These results
      demonstrate the feasibility for using suspended cell aggregates as an
      immobilization system to facilitate perfusion in stirred tank bioreactors, and
      improve volumetric productivities by eliminating the cell density effect.

PMID- 19393553
TI  - Improvement of FR901379 production by mutant selection and medium optimization.
AB  - FR901379 (WF11899A) is a novel echinocandin type of lipopeptide antibiotic
      produced by Coleophoma empetri F-11899. Micafungin (FK463) is derived from the
      chemical modification of deacylated FR901379. In the present paper, we performed
      seven generation's strain-breeding, beginning with a wild type, was performed.
      Selection medium for screening and production medium for high FR901379 production
      were designed. Sodium chloride content in the selection plate was affected to
      FR901379 production and shrinkage of the colony size was observed in high
      producing strains. As selection markers, large colony-shrinking rate and large
      inhibition circle in the agar-piece method using C. albicans was selected. Using
      CMA medium with high sodium chloride, 3 mutants, M-1 to M-3, have achieved a high
      FR901379 production and M-3 showed 5.0 U/mL, while 1.0 U/mL of production was
      achieved in wild type strain. A-2 medium supplemented with 6% of soluble starch
      as a carbon source and 0.6% of ammonium sulfate as nitrogen source was also
      further effective for mutant screening. The FR901379 production of mutant M-4
      (fourth generation) increased until 16.0 U/mL. The concentration of the phosphate
      salt in the medium seemed to inhibit the growth so as to extend the culture
      period. When the A-3 medium supplemented with low concentration of phosphate salt
      and magnesium sulfate as a sulfate source was designed and used, mutants with
      improved production were successively obtained. Finally, variant strain M-7
      showed 30.0 U/mL of production, which was about 30 times higher than that of the
      wild strain.

PMID- 19393554
TI  - Effect of CO2 concentration on the growth and exopolysaccharide production of
      Bifidobacterium longum cultivated under anaerobic conditions.
AB  - For substantial cell growth and exopolysaccharide (EPS) production of
      Bifidobacterium longum JBL05, anaerobic conditions (dissolved oxygen
      concentrations below 0.05 ppm) and the supplement of CO2 (> or = 20%) were
      required. Under these conditions, B. longum JBL05 produced EPS amounts of up to
      2.9 g/l.

PMID- 19393555
TI  - Characterization of glutamate decarboxylase mediating gamma-amino butyric acid
      increase in the early germination stage of soybean (Glycine max [L.] Merr).
AB  - Glutamate decarboxylase (GAD) is an enzyme that catalyzes the production of gamma
      amino butyric acid (GABA) from glutamate through a decarboxylation reaction. A
      full-length cDNA encoding glutamate decarboxylase (GmGAD1) was isolated from
      germinating soybean seeds (Glycine max [L.] Merr.). The GmGAD1 gene had a 1512-bp
      open reading frame, which encodes 503 amino acids. According to its sequence
      similarity with other GAD genes, GmGAD1 was classified into GAD1 in the plant GAD
      family. Recombinant GmGAD1 protein expressed in E. coli catalyzed alpha
      decarboxylation of glutamic acid. The levels of GABA were rapidly increased in
      soybean seeds during the early imbibition period (6 h) of germination or during
      the soaking treatment, whereas mRNA of GmGAD1 gene was not detected in these
      materials. The GmGAD1 protein was observed in seeds of various states such as
      developing, matured and soaking. These data suggest that the increased levels of
      GABA during the early stage of germination or soaking treatment were mediated by
      GmGAD1 protein synthesized in developing soybean seeds.

PMID- 19393556
TI  - Morphological evaluation of chondrogenic potency in passaged cell populations.
AB  - The present study describes the morphological assessment of chondrogenic potency
      during a cell expanding process through serial subculturing of rabbit
      chondrocytes at different levels of population doublings (PD) in a T-flask with a
      conventional polystyrene surface. The passaged populations were seeded on a high
      density collagen surface (CL surface) and in a collagen gel (CL gel) scaffold to
      evaluate the planar and spatial morphologies of the chondrocytes, respectively,
      as well as the gene expressions of mRNA for collagen types I and II. The planar
      morphological estimation was based on roundness (R(c)) of chondrocyte cells at
      different PD values after 1 day incubation on the CL surface. The frequency of
      round-shaped cells with R(c)>0.9 (f(R)) decreased with increasing PD values,
      accompanied by an increase in collagen type I mRNA level. At PD=17.8, the
      frequency reached f(R)=0.12, which was less than one-sixth of that at PD=0. A
      similar trend was found with respect to the passaged chondrocytes embedded in the
      CL gels by estimating the spatial morphology in terms of sphericity (S(c))
      determined 4 days after seeding. With an increase in PD value, the frequency in
      spherical-shaped cells with S(c)>0.9 (f(S)) decreased and the mRNA expression of
      collagen type I increased, giving f(S)=0.28 at PD=17.8 which was less than a
      quarter of that at PD=0. From these results, the cell morphologies on the CL
      surface and in the CL gel were proposed as indicators for understanding
      chondrogenic potentials concerning the phenotypes and differentiated states in
      the population during cell expansion, ultimately leading to quality control of
      tissue-engineered cartilage.

PMID- 19393557
TI  - Evaluation of a bioreactor with stacked sheet shaped organoids of primary
      hepatocytes.
AB  - Hepatocyte organoids have an in vivo-like cell morphology and maintain cell
      viability and function in vitro. On the other hand, the oxygen supply to
      hepatocytes is sometimes limited in the core of organoids that are more than 100
      mum in thickness. In this study, we designed and examined a new bioreactor using
      sheet-shaped organoids (organoid-sheets) in which the thickness was controlled to
      prevent hepatocyte death in the core of organoid due to limitation of oxygen
      supply. The cell culture space consisted of stacked organoid formation spaces and
      medium flow channels. Each space was separated by flat porous polycarbonate
      membranes, and the organoid thickness was controlled at 100 microm with a
      stainless steel spacer. Freshly isolated hepatocytes (7.0 x 10(7)) were
      immobilized in the bioreactor, yielding a cell density of 4.5 x 10(7) cells/cm(3)
      bioreactor. Of the five flow rates tested (1.0, 5.0, 10, 20, and 50 mL/min), the
      bioreactor with the 10 mL/min had the highest ammonia removal and albumin
      secretion activities for at least 14 days. In conclusion, a new bioreactor
      controlling organoid thickness is useful for achieving high cell density culture
      and the maintenance of hepatocyte function to avoid cell death in the core of the
      organoids due to limitation of oxygen supply. The bioreactor may be useful for
      the development of various applications using cultured hepatocytes.

PMID- 19393558
TI  - Monitoring of inflammatory mediators induced by silk sericin.
AB  - Silk proteins have been shown to be good candidates for biomedical materials.
      However, there have been some reports regarding immunological and allergic
      responses to silk sericin. Our objective was to investigate the inflammatory
      mediators induced by sericin both in vitro and in vivo. Mouse monocyte and
      alveolar macrophage cell lines were used for monitoring levels of interleukin
      (IL)-1beta and tumor necrosis factor (TNF)-alpha generated after activation by
      sericin at concentrations of 0.2-1.0 mg/mL. The amounts of TNF-alpha and IL-1beta
      produced by both cell lines corresponded, in a dose-dependent manner, with the
      sericin concentration in the culture medium. The levels of TNF-alpha and IL-1beta
      generated after sericin activation by macrophage cells were higher than those
      generated by monocytes. However, these cytokine levels would not cascade to other
      inflammatory effects. Inflammatory mediators were also monitored from sericin
      treated, cream base-treated and normal saline-soaked full-thickness rat
      excisions. Using wound size measurements and ELISA assays, sericin-treated wounds
      were shown to heal faster and had lower levels of inflammatory mediators, as
      compared with the cream base-treated and normal saline-soaked wounds. It can be
      concluded that sericin promotes the wound healing process without causing
      inflammation.

PMID- 19393560
TI  - Prediction of non-canonical polyadenylation signals in human genomic sequences
      based on a novel algorithm using a fuzzy membership function.
AB  - Computational prediction of polyadenylation signals (PASes) is essential for
      analysis of alternative polyadenylation that plays crucial roles in gene
      regulations by generating heterogeneity of 3'-UTR of mRNAs. To date, several
      algorithms that are mostly based on machine learning methods have been developed
      to predict PASes. Accuracies of predictions by those algorithms have improved
      significantly for the last decade. However, they are designed primarily for
      prediction of the most canonical AAUAAA and its common variant AUUAAA whereas
      other variants have been ignored in their predictions despite recent studies
      indicating that non-canonical variants of AAUAAA are more important in the
      polyadenylation process than commonly recognized. Here we present a new algorithm
      "PolyF" employing fuzzy logic to confer an advance in computational PAS
      prediction--enable prediction of the non-canonical variants, and improve the
      accuracies for the canonical A(A/U)UAAA prediction. PolyF is a simple
      computational algorithm that is composed of membership functions defining
      sequence features of downstream sequence element (DSE) and upstream sequence
      element (USE), together with an inference engine. As a result, PolyF successfully
      identified the 10 single-nucleotide variants with approximately the same or
      higher accuracies compared to those for A(A/U)UAAA. PolyF also achieved higher
      accuracies for A(A/U)UAAA prediction than those by commonly known PAS finder
      programs, Polyadq and Erpin. Incorporating the USE into the PolyF algorithm was
      found to enhance prediction accuracies for all the 12 PAS hexamers compared to
      those using only the DSE, suggesting an important contribution of the USE in the
      polyadenylation process.

PMID- 19393559
TI  - Analysis of the inhibitory mechanism of D-allose on MOLT-4F leukemia cell
      proliferation.
AB  - D-Allose, the C-3 epimer of D-glucose, is one of the rare sugars found in nature.
      In the present study, we have elucidated for the first time that various leukemia
      cell lines have different susceptibility to anti-proliferative activity of D
      allose, and that this difference is related to the difference in induction of
      thioredoxin interacting protein (TXNIP) expression. We examined 5 leukemia cell
      lines (MOLT-4F, IM-9, HL-60, BALL-1 and Daudi), and found that MOLT-4F (T-cell
      lymphoblastic leukemia) had the highest susceptibility to D-allose, and that
      Daudi (Burkitt's lymphoma) had the lowest. D-Allose significantly slowed the cell
      cycle progression without causing apoptosis of MOLT-4F cells. Intracellular TXNIP
      expression was specifically and markedly enhanced in MOLT-4F cells by D-allose
      treatment, and subsequent increase of p27(kip1), a cell cycle inhibitor, was
      observed. On the other hand, D-allose did not increase TXNIP and p27(kip1) levels
      at all in Daudi cells. These results indicate that D-allose suppresses MOLT-4F
      cell proliferation possibly by the inhibition of cell cycle progression via
      induction of TXNIP expression.

PMID- 19393561
TI  - Prophylactic effect of Andrographis paniculata extracts against Streptococcus
      agalactiae infection in Nile tilapia (Oreochromis niloticus).
AB  - Six herbs were assessed for their antimicrobial activity against Streptococcus
      agalactiae, a major fish pathogen causing streptococcosis. Each herb was
      extracted with 3 solvents: water, 95% ethanol, and methanol. Using swab paper
      disc assays, aqueous extracts of Andrographis paniculata and Allium sativum
      produced the largest (27.5 mm) and smallest (10.3 mm) inhibition zones,
      respectively. Determination of minimal inhibitory concentration (MIC) of herb
      extracts against S. agalactiae showed that the aqueous extract of A. paniculata
      had the lowest MIC value (31.25 microg/mL). Aqueous extract of A. sativum was the
      only herb extract with a MIC > 500 microg/mL. Based on mortalities in 2 weeks
      after intraperitoneal S. agalactiae injection, the median lethal dose (LD(50)) of
      S. agalactiae for Nile tilapia (Oreochromis niloticus) was 3.79 x 10(5) CFU/mL.
      In vivo experiments showed that fish feed supplemented with either A. paniculata
      leaf powder or dried matter of A. paniculata aqueous extract reduced mortality of
      S. agalactiae infected Nile tilapia. In addition, no mortality was found in fish
      receiving dried matter of A. paniculata aqueous extract supplemented feeds at
      ratios (w/w) of 4:36 and 5:35. During 2 weeks of feeding with A. paniculata
      supplemented feeds, no adverse effects on appearance, behavior, or feeding
      responses were observed.

PMID- 19393562
TI  - This volume on Practical Competencies in Rheumatology is based on the realization
      that learning, teaching and evaluation of rheumatological skills is very much
      based on competencies. Preface.

PMID- 19393563
TI  - How to achieve and enhance professionalism in rheumatology.
AB  - Ensuring and maintaining professionalism in medicine is essential, but there are
      many challenges to the traditional values and methods of achieving this. It is
      important for the specialty of rheumatology to highlight the importance of
      professionalism within training and clinical practice and to encourage ways of
      demonstrating this to patients, public, providers and politicians to gain
      confidence and avoid over-regulation. Professional attitudes, virtues and
      behaviour are key to providing the best standards of care for the large and
      growing number of people with musculoskeletal conditions, in particular, those
      that are long term. This is important not only for those who are directly in our
      care but also for those in the community, where the civic aspects of
      professionalism are central, by generally improving the standards of care through
      education and by raising priority. The tradition of knowing and working closely
      with our patients and their organisations is an important way of acquiring,
      maintaining and demonstrating professionalism within the specialty.

PMID- 19393564
TI  - Competencies in rheumatology: a European framework.
AB  - The aims, structure, methods and educational experiences employed in the training
      of rheumatologists vary from one national programme to another, according to
      traditions, rules and resources. Mutual recognition of titles, the free movement
      of labour and the striving towards for high-quality standards in medical care in
      Europe demand that efforts and progress are made to ensure that similar
      competencies are achieved by different programmes. The European Rheumatology
      Curriculum Framework, developed by the European Board of Rheumatology, is meant
      to be a step towards the harmonization of rheumatology specialist training within
      the European Union, by providing a reference framework to the development and
      benchmarking of national curricula for the specialist training of
      rheumatologists. The European Rheumatology Curriculum Framework has now been
      endorsed by scientific and educational bodies in 17 member countries. It has been
      provided with a contextualized review of good practice in curriculum planning and
      development - the European Board of Rheumatology Educational Guide.

PMID- 19393565
TI  - Joint aspiration and injection and synovial fluid analysis.
AB  - Joint aspiration/injection and synovial fluid (SF) analysis are both invaluable
      procedures for the diagnosis and treatment of joint disease. This chapter
      addresses: (1) the indications, the technical principles and the expected
      benefits and risks of aspiration and injection of intra-articular corticosteroid;
      and (2) practical aspects relating to SF analysis, especially in relation to
      crystal identification. Intra-articular injection of long-acting insoluble
      corticosteroids is a well-established procedure that produces rapid pain relief
      and resolution of inflammation in most injected joints. The knee is the most
      common site to require aspiration, although any non-axial joint is accessible for
      obtaining SF. The technique requires a knowledge of basic anatomy and should not
      be unduly painful for the patient. Provided sterile equipment and a sensible,
      aseptic approach are used, it is very safe. Analysis of aspirated SF is helpful
      in the differential diagnosis of arthritis and is the definitive method for
      diagnosis of septic arthritis and crystal arthritis. The gross appearance of SF
      can provide useful diagnostic information in terms of the degree of joint
      inflammation and presence of haemarthrosis. Microbiological studies of SF are the
      key to the confirmation of infectious conditions. Increasing joint inflammation
      is associated with increased SF volume, reduced viscosity, increasing turbidity
      and cell count, and increasing ratio of polymorphonuclear: mononuclear cells, but
      such changes are non-specific and must be interpreted in the clinical setting.
      However, detection of SF monosodium urate and calcium pyrophosphate dihydrate
      crystals, even from un-inflamed joints during intercritical periods, allow a
      precise diagnosis of gout and of calcium pyrophosphate crystal-related arthritis.

PMID- 19393566
TI  - How to perform local soft-tissue glucocorticoid injections.
AB  - Inflammation of periarticular soft-tissue structures such as tendons, tendon
      sheaths, entheses, bursae, ligaments and fasciae are the hallmark of many
      inflammatory rheumatic diseases, but inflammation - or rather irritation - of
      these structures also occurs in the absence of an underlying rheumatic disease.
      In both these primary and secondary soft-tissue lesions, local glucocorticoid
      injection often is beneficial, although evidence in literature is limited. This
      chapter reviews local injection therapy for these lesions and for nerve
      compression syndromes.

PMID- 19393567
TI  - How to perform and analyse synovial biopsies.
AB  - Although most of the rheumatologic diseases can be diagnosed based on clinical
      examination combined with additional laboratory and radiographic tests,
      histological examination of synovial tissue may lead to the correct diagnosis and
      adjustment of therapy when neoplastic or granulomatous disease, deposition
      disease, or infection in spite of negative synovial fluid culture is suspected.
      For research purposes synovial tissue analysis is used to investigate the
      pathological changes of the synovium in studies aimed at elucidating the etiology
      and pathogenetic mechanisms involved in arthritis. In addition, the use of
      synovial biomarkers has been shown to be instrumental in the developmental
      process of new therapeutics. In this chapter, several minimally invasive
      techniques for acquiring synovial tissue samples, handling of the tissue, and the
      analysis thereof are described.

PMID- 19393568
TI  - How to perform and analyse biopsies in relation to connective tissue diseases.
AB  - Rheumatic and, in particular, connective tissue diseases involve many organ
      systems in addition to the joints. These include the skin and underlying tissues,
      muscles, salivary glands, nerves, kidneys and blood vessels. Biopsy specimens of
      these tissues can be helpful in establishing a diagnosis, assessing the extent
      and severity of organ involvement and monitoring therapy. This article describes
      the practical information on a clinical diagnosis that might indicate a need for
      biopsy. It outlines how to prepare the patient, how to perform the biopsy, what
      results are to be expected and which sequelae are possible.

PMID- 19393569
TI  - Becoming a musculoskeletal ultrasonographer.
AB  - Over the last decade, increasing numbers of rheumatologists have incorporated
      musculoskeletal ultrasound (MSUS) as a valuable diagnostic tool into their
      clinical practice. Some countries have established training programmes for MSUS.
      The European League Against Rheumatism has developed education guidelines for the
      content and conducting of MSUS courses and it would be useful to standardize
      rheumatology MSUS training worldwide. A thorough knowledge of sectional anatomy,
      ultrasound physics and technology, joint US scanning methods, the sonographic
      pattern of normal and pathological musculoskeletal tissues, artefacts, diagnostic
      criteria and Doppler technique are necessary to perform efficient MSUS. MSUS
      training includes attending theoretical and practical courses, as well as
      studying textbooks, DVDs or websites. Having access to US equipment and
      performing supervised normal and pathological MSUS examinations for a training
      period is mandatory for consolidating MSUS learning. A proposal to accredit and
      certificate competence in MSUS is now being discussed.

PMID- 19393570
TI  - How to perform ultrasound-guided injections.
AB  - Among the most important reasons for the increased use of ultrasound by
      rheumatologists is its feasibility to guide injections. Correct positioning of
      the needle in the targeted structure occurs much more frequently with ultrasound
      guidance than with conventional positioning without imaging. The sonographer can
      mark the skin above the structure, using ultrasound to localize this point and to
      estimate the depth of the structure. Alternatively, the sonographer might
      introduce the needle under direct sonographic visualisation, holding the probe in
      one hand and the needle in the other. The needle can be longitudinally parallel
      to the probe, with an angle of about 45 degrees to the probe. It can be
      introduced close to the middle of the probe or opposite the probe; the needle can
      be also depicted transversely. Ultrasound allows needle guidance in nearly all
      important structures of shoulders, elbows, hand, hips, knees and feet. Education
      involves training to coordinate probe and needle in sponges, chicken, cheese and
      other objects. Knowledge of anatomy, probe positioning and the ability to
      coordinate probe and needle are necessary when injecting patients with
      sonographic guidance. The rheumatologist might start with easy approaches in
      which the needle is parallel to the probe.

PMID- 19393571
TI  - How to keep up with medical literature.
AB  - All medical practice and research should aim to be evidence based, as far as this
      is possible. The first step to achieve this is to keep up with what is already
      known. With medical knowledge growing constantly, it has become necessary to
      possess a high level of information literacy to be able to keep up with the
      literature. Furthermore, as patients can now search for information on the
      internet, clinicians must be able to respond to this type of information in a
      professional way when needed. Here, the development of viable search strategies
      for journal articles, books, book chapters and similar sources, selection of
      appropriate databases, search tools and selection methods are described and
      illustrated with examples from rheumatology. Further, the up-keep of skills over
      time, and the acquisition of literature just in time, are discussed.

PMID- 19393572
TI  - How to perform a critical analysis of a randomised controlled trial.
AB  - Given the large amount of medical literature of varying methodological quality,
      care must be taken when translating the results of randomised controlled trials
      into clinical practice. To assist in this translation process, we provide a
      method that involves answering three main questions: 'Can I trust the results?'
      'How do I understand the results?' and 'To whom do the results apply?' To answer
      the first question, we describe important items that help in judging the
      reliability of the findings. For the second question, we address the clinical and
      statistical significance of results by looking at the size and precision of the
      effect. Finally, we raise the issue of external validity and of reporting adverse
      effects to determine which patients may best benefit from the new intervention.

PMID- 19393581
TI  - Ectopic expression of plasma membrane targeted subunits of the Ndc80-complex as a
      tool to study kinetochore biochemistry.
AB  - Genomic stability depends on the normal function of the kinetochore, a multi
      protein assemblage, which consists of over 80 molecules including both
      constitutive and transiently binding components. Information regarding the
      spatial-temporal assembly of kinetochore subcomplexes is often limited by
      technical difficulties in their isolation. To study kinetochore subcomplex
      formation, we targeted separately Hec1 and Spc24, two subunits of the Ndc80
      kinetochore compilation, to the plasma membrane by fusing them with the amino
      terminal palmitoylation and myristoylation (pm) sequence of the receptor tyrosine
      kinase Fyn. We found that in early mitotic cells, pm-GFP-Hec1 and pm-GFP-Spc24
      fusion proteins localised to the plasma membrane and were able to recruit all
      subunits of the Ndc80 complex (Ndc80/Hec1, Nuf2, Spc24 and Spc25) to these foci.
      In interphase cells, only Hec1-Nuf2 and Spc24-Spc25 heterodimers accumulated to
      the plasma membrane foci. The results propose that the assembly of Ndc80 tetramer
      can take place outside of the kinetochore but requires co-factors that are only
      present in mitotic cells. These findings provide the first experimental evidence
      on the successful employment of the plasma membrane targeting technique in the
      study of kinetochore biochemistry.

PMID- 19393580
TI  - Neurotensin signaling induces intracellular alkalinization and interleukin-8
      expression in human pancreatic cancer cells.
AB  - Pancreatic adenocarcinomas express neurotensin receptors in up to 90% of cases,
      however, their role in tumor biology and as a drug target is not clear. In the
      present study, a stable neurotensin (NT) analog induced intracellular calcium
      release and intracellular alkalinization in BxPC-3 and PANC-1 pancreatic cancer
      cells that was abolished by inhibitors of NT receptor (NTR) and sodium-proton
      exchanger 1 (NHE1), amiloride and SR 142948, respectively. Activation of NHE1
      involved increased phosphorylation of dimethylfumarate-sensitive mitogen- and
      stress-activated kinase 1/2 (MSK1/2). NTR signaling appears to promote a
      metastatic phenotype in pancreatic cancer cells by induction of localized
      extracellular acidification in normoxic cells, preceeding acidosis induced by
      hypoxia and switch to glycolysis in addition to increased expression of
      interleukin-8 (IL-8).

PMID- 19393582
TI  - Has the US Cancer Centre model been 'successful'? Lessons for the European cancer
      community.
AB  - The US model of Cancer Centres created by the National Cancer Act in 1971 has
      been one of the most tried and tested models of organised disease-specific
      scientific endeavors in the world. With many countries, particularly those in
      Europe now looking to develop the research arms of their National Cancer Control
      Programmes through the development of similar Cancer Centres the time is correct
      to consider the success and limitations of the US effort to date. Here we
      described the salient features of both US Cancer Centres and Networks, including
      their funding and evaluation with socio-political analysis on the learning points
      for Europe. In particular we highlight issues around sustainable funding,
      training and network development. New data highlighting deficiencies in the US
      model around prevention, health promotion, health inequalities in cancer
      outcomes, and clinical research provide key learning points and opportunities for
      the European model developed.

PMID- 19393583
TI  - Molecular characterization of apocrine carcinoma of the breast: validation of an
      apocrine protein signature in a well-defined cohort.
AB  - Invasive apocrine carcinomas (IACs), as defined by morphological features,
      correspond to 0.3-4% of all invasive ductal carcinomas (IDC), and despite the
      fact that they are histologically distinct from other breast lesions there are
      currently no standard molecular criteria available for their diagnosis and no
      unequivocal information as to their prognosis. In an effort to address these
      concerns we have been using protein expression profiling technologies in
      combination with mass spectrometry and immunohistochemistry (IHC) to discover
      specific biomarkers that could allow us to molecularly characterize these lesions
      as well as to dissect some of the steps in the processes underlying breast
      apocrine metaplasia and development of precancerous apocrine lesions.
      Establishing these apocrine-specific markers as best practice for the routine
      pathology evaluation of breast cancer, however, will require their validation in
      large cohorts of patients. Towards this goal we have composed a panel of
      antibodies against components of an apocrine protein signature that includes
      probes against the apocrine-specific markers 15-prostaglandin dehydrogenase (15
      PGDH), and acyl-CoA synthetase medium-chain family member 1 (ACSM1), in addition
      to a set of categorizing markers that are consistently expressed (AR, CD24) or
      not expressed (ERalpha, PgR, Bcl-2, and GATA-3) by apocrine metaplasia in benign
      breast lesions and apocrine sweat glands. This panel was used to analyze a well
      defined cohort consisting of 14 apocrine ductal carcinoma in situ (ADCIS), and 33
      IACs diagnosed at the Cancer Institute Hospital, Tokyo between 1997 and 2001.
      Samples were originally classified on the basis of cellular morphology with all
      cases having more than 90% of the tumour cells exhibiting cytological features
      typical of apocrine cells. Using the expression of 15-PGDH and/or ACSM1 as the
      main criterion, but taking into account the expression of other markers, we were
      able to identify unambiguously 13 out of 14 ADCIS (92.9%) and 20 out of 33
      (60.6%) IAC samples, respectively, as being of apocrine origin. Our results
      demonstrate that IACs correspond to a distinct, even if heterogeneous, molecular
      subgroup of breast carcinomas that can be readily identified in an unbiased way
      using a combination of markers that recapitulate the phenotype of apocrine sweat
      glands (15-PGDH(+), ACSM1(+), AR(+), CD24(+), ERalpha(-), PgR(-), Bcl-2(-), and
      GATA-3(-)). These results pave the way for addressing issues such as prognosis of
      IACs, patient stratification for targeted therapeutics, as well as research
      strategies for identifying novel therapeutic targets for developing new cancer
      therapies.

PMID- 19393584
TI  - Discovery of epitopes for targeting the human epidermal growth factor receptor 2
      (HER2) with antibodies.
AB  - Antibodies have become valuable therapeutic agents for targeting of extracellular
      proteins in various diseases, including cancer, autoimmunity and cardiovascular
      disorders. For breast cancer, antibodies targeting the human HER2 have been shown
      to result in cell growth inhibition both in vitro and in patients with breast
      tumors. There is evidence to suggest that targeting multiple HER2 epitopes may
      result in increased growth inhibition making it interesting to find antibodies
      targeting new epitopes. Here, we report on a new scheme to discover antibodies
      directed to new epitopes using the extracellular domain of the HER2 as a model.
      Polyclonal antibodies were generated using recombinant protein fragments and
      affinity purified fractions of the antibodies were functionally characterized and
      precisely epitope mapped using bacterial surface display. Polyclonal antibodies
      towards a 127 amino acid recombinant protein fragment spanning between domains II
      and III of the HER2 were shown to bind to human ductal carcinoma cell line BT474
      resulting in growth inhibition. Affinity purification demonstrated that
      antibodies to two separate regions from the N- and C-terminal end of the fragment
      exhibited the growth inhibition. Epitope mapping of the C-terminal antibodies
      revealed a 25 amino acid region (LPESFDGDPASNTAPLQPEQLQVF) with two distinct
      epitopes mediating efficient growth inhibition. The results suggest that
      antibodies directed towards this region of domain III of the HER2, distinct from
      the well-known monoclonal antibodies trastuzumab and pertuzumab, bind to the HER2
      on living cells and exhibit growth inhibition. The work describes a new strategy
      to develop antibodies directed to non-overlapping epitopes and shows a path of
      pursuit to explore the epitope space of a target protein.

PMID- 19393588
TI  - Stem cell decision making and critical-like exploratory networks.
AB  - A sound theoretical or conceptual model of gene regulatory processes that control
      stem cell fate is still lacking, compromising our ability to manipulate stem
      cells for therapeutic benefit. The complexity of the regulatory and signaling
      pathways limits development of useful, predictive models that employ solely
      reductionist methods using molecular components. However, there is clear evidence
      from other complex systems that coarse-grained or mesoscale models can yield
      useful insights and provide workable models for the prediction of some emergent
      properties such as cell phenotype. We present such a coarse-grained model of stem
      cell decision making, utilizing the concept of self-organized criticality, which
      is an order that propagates in some nonequilibrium systems. The model proposes
      that stochastic gene expression within a stem cell gene regulatory network self
      organizes to a critical-like state, characterized by cascades of gene expression
      that prime various transcriptional programs associated with different cell fates.
      This diversity of cell fate options is reduced during the decision-making
      process, which involves a supercritical connectivity in the gene regulatory
      network as a stem cell leaves its niche microenvironment and an overall increase
      in transcription occurs. As modules of genes that correspond to specific cell
      fates approach their critical points, competitive interactions occur between them
      that are influenced by prevailing microenvironmental conditions. The conceptual
      model incorporates both intrinsic and extrinsic factors governing stem cell fate
      and provides a logical pathway to the development of a computational model. We
      further suggest that rapid self-organized criticality, rather than self-organized
      criticality, best describes the mesoscale organization of gene regulatory
      networks.

PMID- 19393585
TI  - Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530.
AB  - AZD0530, an orally available Src inhibitor, demonstrated potent antimigratory and
      anti-invasive effects in vitro, and inhibited metastasis in a murine model of
      bladder cancer. Antiproliferative activity of AZD0530 in vitro varied between
      cell lines (IC(50) 0.2 ->10MUM). AZD0530 inhibited tumor growth in 4/10 xenograft
      models tested and dynamically inhibited in vivo phosphorylation of Src substrates
      paxillin and FAK in both growth-inhibition-resistant and -sensitive xenografts.
      The activity of AZD0530 in NBT-II bladder cancer cells in vitro was consistent
      with inhibition of cell migration and stabilization of cell-cell adhesion. These
      data suggest a dominant anti-invasive pharmacology for AZD0530 that may limit
      tumor progression in a range of cancers. AZD0530 is currently in Phase II
      clinical trials.

PMID- 19393589
TI  - Tracking the cell hierarchy in the human intestine using biochemical signatures
      derived by mid-infrared microspectroscopy.
AB  - Markers of gastrointestinal (GI) stem cells remain elusive. We employed
      synchrotron Fourier-transform infrared (FTIR) microspectroscopy to derive mid
      infrared (IR) spectra along the length of human GI crypts. Tissue sections (10
      MUm thick) were floated onto BaF2 windows and image maps were acquired of small
      intestine and large bowel crypts in transmission mode with an aperture of <=10
      MUm*10 MUm. Counting upwards in a step-size (<=10 MUm) fashion from the crypt
      base, IR spectra were extracted from the image maps and each spectrum
      corresponding to a particular location was identified. Spectra were analyzed
      using principal component analysis plus linear discriminant analysis. Compared to
      putative crypt base columnar/Paneth cells, those assigned as label-retaining
      cells were chemically more similar to putative large bowel stem cells and, the
      small intestine transit-amplifying cells were closest to large bowel transit
      amplifying cells; interestingly, the base of small intestine crypts was the most
      chemically-distinct. This study suggests that in the complex cell lineage of
      human GI crypts, chemical similarities as revealed by FTIR microspectroscopy
      between regions putatively assigned as stem cell, transit-amplifying and
      terminally-differentiated facilitates identification of cell function.

PMID- 19393590
TI  - Long-term microcarrier suspension cultures of human embryonic stem cells.
AB  - The conventional method of culturing human embryonic stem cells (hESC) is on two
      dimensional (2D) surfaces, which is not amenable for scale up to therapeutic
      quantities in bioreactors. We have developed a facile and robust method for
      maintaining undifferentiated hESC in three-dimensional (3D) suspension cultures
      on matrigel-coated microcarriers achieving 2- to 4-fold higher cell densities
      than those in 2D colony cultures. Stable, continuous propagation of two hESC
      lines on microcarriers has been demonstrated in conditioned media for 6 months.
      Microcarrier cultures (MC) were also demonstrated in two serum-free defined media
      (StemPro and mTeSR1). MC achieved even higher cell concentrations in suspension
      spinner flasks, thus opening the prospect of propagation in controlled
      bioreactors.

PMID- 19393591
TI  - Establishment and characterization of baboon embryonic stem cell lines: an Old
      World Primate model for regeneration and transplantation research.
AB  - Here we have developed protocols using the baboon as a complementary alternative
      Old World Primate to rhesus and other macaques which have severe limitations in
      their availability. Baboons are not limited as research resources, they are
      evolutionarily closer to humans, and the multiple generations of pedigreed
      colonies which display complex human disease phenotypes all support their further
      optimization as an invaluable primate model. Since neither baboon-assisted
      reproductive technologies nor baboon embryonic stem cells (ESCs) have been
      reported, here we describe the first derivations and characterization of baboon
      ESC lines from IVF-generated blastocysts. Two ESCs lines (BabESC-4 and BabESC-15)
      display ESC morphology, express pluripotency markers (Oct-4, hTert, Nanog, Sox-2,
      Rex-1, TRA1-60, TRA1-81), and maintain stable euploid female karyotypes with
      parentage confirmed independently. They have been grown continuously for >430 and
      290 days, respectively. Teratomas from both lines have all three germ layers.
      Availabilities of these BabESCs represent another important resource for stem
      cell biologists.

PMID- 19393592
TI  - Characterization of human UTF1, a chromatin-associated protein with repressor
      activity expressed in pluripotent cells.
AB  - In mice, during early embryonic development UTF1 (undifferentiated embryonic cell
      transcription factor 1) is expressed in the inner cell mass of blastocysts and in
      adult animals expression is restricted to the gonads. (Embryonic) Cells
      expressing UTF1 are generally considered pluripotent, meaning they can
      differentiate into all cell types of the adult body. In mouse it was shown that
      UTF1 is tightly associated with chromatin and that it is required for proper
      differentiation of embryonic carcinoma and embryonic stem cells. In this study we
      functionally characterized the human UTF1 protein. We show with localization,
      subnuclear fractionation, and strip-FRAP analyses that human UTF1 is a tightly
      DNA-associated protein with transcriptional repressor activity. Our data identify
      human UTF1 as a pluripotency-associated chromatin component with core histone
      like characteristics.

PMID- 19393593
TI  - Teratoma formation by human embryonic stem cells: evaluation of essential
      parameters for future safety studies.
AB  - Transplantation of human embryonic stem cells (hESC) into immune-deficient mice
      leads to the formation of differentiated tumors comprising all three germ layers,
      resembling spontaneous human teratomas. Teratoma assays are considered the gold
      standard for demonstrating differentiation potential of pluripotent hESC and hold
      promise as a standard for assessing safety among hESC-derived cell populations
      intended for therapeutic applications. We tested the potency of teratoma
      formation in seven anatomical transplantation locations (kidney capsule, muscle,
      subcutaneous space, peritoneal cavity, testis, liver, epididymal fat pad) in SCID
      mice with and without addition of Matrigel, and found that intramuscular teratoma
      formation was the most experimentally convenient, reproducible, and quantifiable.
      In the same experimental setting, we compared undifferentiated hESC and
      differentiated populations enriched for either beating cardiomyocytes or
      definitive endoderm derivatives (insulin-secreting beta cells), and showed that
      all cell preparations rapidly formed teratomas with varying percentages of
      mesoderm, ectoderm, and endoderm. In limiting dilution experiments, we found that
      as little as two hESC colonies spiked into feeder fibroblasts produced a
      teratoma, while a more rigorous single-cell titration achieved a detection limit
      of 1/4000. In summary, we established core parameters essential for facilitating
      safety profiling of hESC-derived products for future therapeutic applications.

PMID- 19393594
TI  - Clinically failed eggs as a source of normal human embryo stem cells.
AB  - The promise of human embryo stem cells (hESCs) for regenerative medicine is
      offset by the ethical and practical challenges involved in sourcing eggs and
      embryos for this objective. In this study we sought to isolate an hESC line from
      clinically failed eggs, the usage of which would not conflict with donor
      interests to conceive. A total of 8 blastocysts were allocated for hESC
      derivation from a pool of 579 eggs whose fertilization had been clinically
      assessed to have occurred abnormally (i.e., three pronuclei) or failed (i.e., no
      pronuclei) following in vitro insemination or intracytoplasmic sperm injection
      (ICSI). The latter were subjected to a recovery intervention consisting of either
      reinsemination by ICSI or parthenogenetic stimulation. One hESC line (RCM1) was
      obtained from a failed-to-fertilize inseminated egg recovered by parthenogenetic
      activation. Standard in vitro and in vivo characterization revealed this line to
      possess all of the properties attributed to a normal euploid hESC line. Whole
      genome single-nucleotide polymorphism analysis further revealed that the line was
      biparental, indicating that sperm penetration had occurred, although
      parthenogenetic stimulation was required for activation. Our results demonstrate
      the viability of an alternative strategy to generate normal hESC lines from
      clinically failed eggs, thereby further minimizing the potential to conflict with
      donor reproductive interest to conceive.

PMID- 19393595
TI  - Significant linkage evidence for a predisposition gene for pelvic floor disorders
      on chromosome 9q21.
AB  - Predisposition factors for pelvic floor disorders (PFDs), including pelvic organ
      prolapse (POP), stress urinary incontinence (SUI), urge urinary incontinence
      (UUI), and hernias, are not well understood. We assessed linkage evidence for
      PFDs in mostly sister pairs who received treatment for moderate-to-severe POP. We
      genotyped 70 affected women of European descent from 32 eligible families with at
      least two affected cases by using the Illumina 1 million single-nucleotide
      polymorphism (SNP) marker set. Parametric linkage analysis with general dominant
      and recessive models was performed by the Markov chain Monte Carlo linkage
      analysis method, MCLINK, and a set of SNPs was formed, from which those in high
      linkage disequilibrium were eliminated. Significant genome-wide evidence for
      linkage was identified on chromosome 9q21 with a HLOD score of 3.41 under a
      recessive model. Seventeen pedigrees (53%) had at least nominal evidence for
      linkage on a by-pedigree basis at this region. These results provide evidence for
      a predisposition gene for PFDs on chromosome 9q.

PMID- 19393596
TI  - De novo stress incontinence and pelvic muscle symptoms after transvaginal mesh
      repair.
AB  - OBJECTIVE: We sought to determine the rate of de novo stress incontinence, pelvic
      muscle symptoms, mesh exposure, visceral injury rate, and recurrent prolapse
      after transvaginal mesh repair. STUDY DESIGN: We conducted a retrospective review
      of 335 consecutive women with stage II or worse vaginal prolapse who underwent
      Prolift (Ethicon, Somerville, NJ) between July 7, 2005 and Jan. 31, 2008.
      RESULTS: In all, 71% underwent total Prolift, 20% anterior, and 8% posterior
      alone. Average age was 62 years and mean follow-up was 8 months. The
      intraoperative visceral injury rate was 6.6%, mesh exposure rate was 3.8%, and
      recurrent failure rate was 5.2%. The postoperative de novo stress incontinence
      rate was 24.3%. In this series, 18% of women had pelvic muscle symptoms
      postoperatively; 74% of these resolved within 6 months with conservative
      management. CONCLUSION: After Prolift, surgeons can expect a low rate of
      recurrent prolapse and mesh exposure. However, pelvic muscle dysfunction and de
      novo stress incontinence will be encountered postoperatively in a moderate number
      of women.

PMID- 19393597
TI  - Methotrexate for 2000 FIGO low-risk gestational trophoblastic neoplasia patients:
      efficacy and toxicity.
AB  - OBJECTIVE: We sought to review efficacy and toxicity of an 8-day methotrexate
      (MTX) regimen in the treatment of patients with low-risk gestational
      trophoblastic neoplasia (GTN) from the French Trophoblastic Disease Reference
      Center. STUDY DESIGN: Between 1999 and 2006, 142 low-risk GTNs were diagnosed
      according to International Federation of Gynecology and Obstetrics (FIGO)
      criteria for GTN and to the FIGO scoring system. We report their characteristics,
      remission/resistance/recurrence rates, and treatment toxicity. RESULTS: The 8-day
      MTX regimen achieved a 77.5% remission rate. All patients but 1 (99.9%) achieved
      remission and remained disease free until the time of analysis. Severe (grade 3
      or 4) blood/bone marrow toxicity and metabolic/laboratory toxicity was noted in
      4.2% of cases, of which 2 (1.4%) were grade 4. CONCLUSION: For patients with GTN
      diagnosed according to FIGO criteria and considered low risk according to the
      FIGO scoring system, an 8-day MTX regimen is an adequate treatment associating a
      high rate of remission to a low rate of toxicity.

PMID- 19393600
TI  - Incidence of endometrial hyperplasia.
AB  - OBJECTIVE: The objective of the study was to estimate the age-specific incidence
      of endometrial hyperplasia: simple, complex, and atypical, in order of increasing
      likelihood of progression to carcinoma. STUDY DESIGN: Women aged 18-90 years with
      endometrial pathology specimens (1985-2003) at a large integrated health plan
      were identified using automated data. Incidence rates were obtained by dividing
      the number of cases by the estimated number of female health plan enrollees who
      retained a uterus. RESULTS: Endometrial hyperplasia peak incidence was: simple,
      142 per 100,000 woman-years, complex, 213 per 100,000 woman-years, both in the
      early 50s; and atypical, 56 per 100,000 woman-years in the early 60s. Age
      adjusted incidence decreased over the study period, especially for atypical
      hyperplasia. CONCLUSION: Endometrial hyperplasia incidence without and with
      atypia peaks in the early postmenopausal years and in the early 60s,
      respectively. Given that some cases of endometrial hyperplasia likely go
      undiagnosed, the figures provided should be viewed as minimum estimates of the
      true incidence.

PMID- 19393601
TI  - Investigation of the sensitivity of a cross-polarized light visualization system
      to detect subclinical erythema and dryness in women with vulvovaginitis.
AB  - OBJECTIVE: An enhanced visualization technique using polarized light (Syris v600
      enhanced visualization system; Syris Scientific LLC, Gray, ME) detects surface
      and subsurface ( approximately 1 mm depth) inflammation. We sought to compare the
      Syris v600 system with unaided visual inspection and colposcopy of the female
      genitalia. STUDY DESIGN: Erythema and dryness of the vulva, introitus, vagina,
      and cervix were visualized and scored by each method in patients with and without
      vulvitis. RESULTS: Subsurface visualization was more sensitive in detecting
      genital erythema and dryness at all sites whether or not symptoms were present.
      Subsurface inflammation of the introitus, vagina, and cervix only was detected
      uniquely in women with vulvar vestibulitis syndrome (VVS). A subset of women
      presenting with VVS exhibited subclinical inflammation of the vulva vestibule and
      vagina (designated VVS/lichen sclerosus subgroup). CONCLUSION: Enhanced
      visualization of the genital epithelial subsurface with cross-polarized light may
      assist in diagnosing subclinical inflammation in vulvar conditions heretofore
      characterized as sensory syndromes.

PMID- 19393602
TI  - Expression, purification, and characterization of exo-beta-D-glucosaminidase of
      Aspergillus sp. CJ22-326 from Escherichia coli.
AB  - An exo-beta-D-glucosaminidase gene was cloned from Aspergillus sp. CJ22-326 and
      expressed in Escherichia coli. The purified protein showed an exo-chitosanase
      activity in a viscosimetric assay and TLC analysis. This is the first report on
      cloning of a gene encoding an Aspergillus sp. exo-beta-D-glucosaminidase.

PMID- 19393604
TI  - Cytoplasmic domain of human Fcalpha/mu receptor is required for ligand
      internalization.
AB  - The Fcalpha/mu receptor (Fcalpha/microR), a type I transmembrane protein, is an
      immunoglobulin Fc receptor for both IgA and IgM. Its functions in immune defense
      are not clear at present. In this work, human Fcalpha/microR was expressed in
      CHO, 293T, and COS-7 cells to study its biochemical functions. Fcalpha/microR
      expressed by CHO and 293T was only in monomer form in cytoplasma and the
      monomeric receptor could not bind IgA or IgM. In comparison, Fcalpha/microR
      expressed by COS-7 cells had both monomer and dimer forms. The binding assay
      showed that Fcalpha/microR expressed by COS-7 cells could bind IgM strongly and
      IgA weakly, implying that dimeric receptor could be expressed on cell membrane
      and functioned. The bound IgM could be internalized and the internalization was
      abolished when the cytoplasmic domain of Fcalpha/microR was truncated. Therefore,
      the cytoplasmic portion of human Fcalpha/microR is required in the
      internalization.

PMID- 19393603
TI  - Tec kinases regulate actin assembly and cytokine expression in LPS-stimulated
      human neutrophils via JNK activation.
AB  - The acute inflammatory response involves neutrophils wherein recognition of
      bacterial products, such as lipopolysaccharide (LPS), activates intracellular
      signaling pathways. We have shown that the mitogen-activated protein kinase
      (MAPK) c-Jun NH(2) terminal kinase (JNK) is activated by LPS in neutrophils and
      plays a critical role in monocyte chemoattractant protein (MCP)-1 expression and
      actin assembly. As the Tec family kinases are expressed in neutrophils and
      regulate activation of the MAPKs in other cell systems, we hypothesized that the
      Tec kinases are an upstream component of the signaling pathway leading to LPS
      induced MAPKs activation in neutrophils. Herein, we show that the Tec kinases are
      activated in LPS-stimulated human neutrophils and that inhibition of the Tec
      kinases, with leflunomide metabolite analog (LFM-A13), decreased LPS-induced JNK,
      but not p38, activity. Furthermore, LPS-induced actin polymerization as well as
      MCP-1, tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta
      expression are dependent on Tec kinase activity.

PMID- 19393605
TI  - The preventive effect of adjuvant-free administration of TNF-PADRE autovaccine on
      collagen-II-induced rheumatoid arthritis in mice.
AB  - Adjuvants are necessary to elicit high titers of antibodies in vaccine
      immunization procedures. We previously developed a mouse tumor necrosis factor
      alpha (TNF-alpha) autovaccine (mTNF-PADRE) capable of inducing anti-TNF-alpha
      antibodies. In this study, we investigated the therapeutic effect of adjuvant
      free administration of the autovaccine on collagen-type-II-induced rheumatoid
      arthritis (CIA) in mice. Our results showed that the vaccine could ameliorate the
      symptoms of CIA in mice. In addition, this study suggests that it is possible to
      control the antibody levels in mice immunized with mTNF-PADRE without adjuvant.

PMID- 19393606
TI  - Microbial tolerance in secondary peritonitis is dose dependent.
AB  - Local microbial tolerance was investigated in a murine model of peritonitis.
      Peritoneal bacterial burden and inflammatory cytokine concentrations were
      determined at different times, within 48h after infection. Peritoneal macrophages
      were harvested from naive mice or from mice 48h after infection and underwent ex
      vivo stimulation with different concentrations of Klebsiella. Cytokine secretion
      was determined in the supernatants. Peritoneal bacteria concentrations, remained
      relatively steady between 24h (median: 5.04 log CFU) and 48h (median: 5.19 log
      CFU) after infection. Peritoneal cytokine concentrations peaked early but were
      already diminished at 48h after infection, despite persistent high bacteria
      levels. Macrophages, harvested from naive mice responded vigorously to ex vivo
      stimulation with 10(5) CFU and 2 x 10(8) CFU Klebsiella. Cells harvested from
      animals 48h after infection, were unresponsive to an ex vivo stimulation with
      10(5) CFU Klebsiella, but fully responded to 10(8) CFU. Persistent intraabdominal
      bacterial infection induced dose dependent microbial tolerance in peritoneal
      macrophages.

PMID- 19393609
TI  - The additional benefit of the ML Flow test to classify leprosy patients.
AB  - The use of the skin lesion counting classification leads to both under and over
      diagnosis of leprosy in many instances. Thus, there is a need to complement this
      classification with another simple and robust test for use in the field. Data of
      202 untreated leprosy patients diagnosed at FIOCRUZ, Rio de Janeiro, Brazil, was
      analyzed. There were 90 patients classified as PB and 112 classified as MB
      according to the reference standard. The BI was positive in 111 (55%) patients
      and the ML Flow test in 116 (57.4%) patients. The ML Flow test was positive in 95
      (86%) of the patients with a positive BI. The lesion counting classification was
      confirmed by both BI and ML Flow tests in 65% of the 92 patients with 5 or fewer
      lesions, and in 76% of the 110 patients with 6 or more lesions. The combination
      of skin lesion counting and the ML Flow test results yielded a sensitivity of 85%
      and a specificity of 87% for MB classification, and correctly classified 86% of
      the patients when compared to the standard reference. A considerable proportion
      of the patients (43.5%) with discordant test results in relation to standard
      classification was in reaction. The use of any classification system has
      limitations, especially those that oversimplify a complex disease such as
      leprosy. In the absence of an experienced dermatologist and slit skin smear, the
      ML Flow test could be used to improve treatment decisions in field conditions.

PMID- 19393610
TI  - LNA flow-FISH: a flow cytometry-fluorescence in situ hybridization method to
      detect messenger RNA using locked nucleic acid probes.
AB  - We present a novel method using flow cytometry-fluorescence in situ hybridization
      (flow-FISH) to detect specific messenger RNA (mRNA) in suspended cells using
      locked nucleic acid (LNA)-modified oligonucleotide probes. beta-Actin mRNA was
      targeted in whole A549 epithelial cells by hybridization with a biotinylated, LNA
      modified probe. The LNA bound to beta-actin was then stained using phycoerythrin
      conjugated streptavidin and detected by flow cytometry. Shifts in fluorescence
      signal intensity between the beta-actin LNA probe and a biotinylated, nonspecific
      control LNA were used to determine optimal conditions for this type of flow-FISH.
      Multiple conditions for permeabilization and hybridization were tested, and it
      was found that conditions using 3 microg/ml of proteinase K for permeabilization
      and 90 min hybridization at 60 degrees C with buffer containing 50% formamide
      allow cells containing the LNA-bound mRNA to be detected and differentiated from
      the control LNA with high confidence (< 14% overlap between curves). This
      combined method, called LNA flow-FISH, can be used for detection and
      quantification of other RNA species as well as for telomerase measurement and
      detection.

PMID- 19393611
TI  - Octadecylsilyl silica column method for extraction of messenger RNA.
AB  - We have developed a simple and rapid method for the purification of poly(A) tail
      messenger RNA (mRNA) from total RNA by using a solid phase extraction column
      filled with a small amount of octadecylsilyl silica. The method is based on a
      hydrophobic interaction between the poly(A) tail and the octadecyl unit on the
      silica particle in a water/dimethyl sulfoxide mixed solution. By using this
      column, mRNA can be separated from 100 microg of total RNA in less than 10 min
      with high yields (>80%).

PMID- 19393612
TI  - A liquid chromatography-tandem mass spectrometry-based assay for indole-3-acetic
      acid-amido synthetase.
AB  - Indole-3-acetic acid (IAA) amide conjugates play an important role in balancing
      levels of free IAA in plant cells. The GH3 family of proteins conjugates free IAA
      with various amino acids. For example, auxin levels modulate expression of the
      Oryza sativa (rice) GH3-8 protein, which acts to prevent IAA accumulation by
      coupling the hormone to aspartate. To examine the kinetic properties of the
      enzyme, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      assay system. Bacterially expressed OsGH3-8 was purified to homogeneity and used
      to establish the assay system. Monitoring of the reaction confirms the reaction
      product as IAA-Asp and demonstrates that production of the conjugate increases
      proportionally with both time and enzyme amount. Steady-state kinetic analysis
      using the LC-MS/MS-based assay yields the following parameters: V/E(t)(IAA)=20.3
      min(-1), K(m)(IAA)=123 microM, V/E(t)(ATP)=14.1 min(-1), K(m)(ATP)=50 microM,
      V/E(t)(Asp)=28.8 min(-1), K(m)(Asp)=1580 microM. This is the first assignment of
      kinetic values for any IAA-amido synthetase from plants. Compared with previously
      described LC- and thin-layer chromatography (TLC)-based assays, this LC-MS/MS
      method provides a robust and sensitive means for performing direct kinetic
      studies on a range of IAA-conjugating enzymes.

PMID- 19393613
TI  - Reactive oxygen species as cardiovascular mediators: lessons from endothelial
      specific protein overexpression mouse models.
AB  - The term reactive oxygen species (ROS) summarizes several small chemical
      compounds such as superoxide, peroxynitrite, hydrogen peroxide and nitric oxide.
      The stoichiometry of the chemical reactions underlying generation and metabolism
      is subject of tight enzymatic regulation resulting in well balanced steady-state
      concentrations throughout the healthy body. ROS are short-lived and usually
      active at the site of production only, e.g. in vascular endothelial cells.
      Although an increase of vascular ROS-production is considered an important
      pathogenic factor in cardiovascular diseases, there is evidence for physiological
      or even beneficial effects as well. We have generated several transgenic mice
      using the Tie-2 promotor which expresses an enzyme of interest specifically in
      vascular endothelial cells. Here, we review some results obtained with mice
      carrying a Tie-2-driven overexpression of catalase or endothelial nitric oxide
      synthase (eNOS). Tie-2-catalase mice have a strongly reduced steady-state
      concentration of vascular hydrogen peroxide and show profound hypotension that is
      not dependent on the bioavailability of endothelial nitric oxide but is
      completely reversible by treatment with the catalase inhibitor aminotriazole. A
      similar hypotension was observed in transgenic mice with an endothelial-specific
      overexpression of eNOS but this hypotension is entirely dependent on vascular
      eNOS activity. These observations suggest a tonic effect of hydrogen peroxide on
      vascular smooth muscle. Further studies suggested that hydrogen peroxide promotes
      the exercise-induced increase of vascular eNOS expression and inhibits the
      release of endothelial progenitor cells induced by exercise training. In summary,
      our data support the concept of a dual role of ROS in the vascular system.

PMID- 19393614
TI  - Mysteries that still remain.

PMID- 19393615
TI  - Membrane interactions of a self-assembling model peptide that mimics the self
      association, structure and toxicity of Abeta(1-40).
AB  - Beta-amyloid peptide (Abeta) is a primary protein component of senile plaques in
      Alzheimer's disease (AD) and plays an important, but not fully understood role in
      neurotoxicity. Model peptides with the demonstrated ability to mimic the
      structural and toxicity behavior of Abeta could provide a means to evaluate the
      contributions to toxicity that are common to self-associating peptides from many
      disease states. In this work, we have studied the peptide-membrane interactions
      of a model beta-sheet peptide, P(11-2) (CH(3)CO-Gln-Gln-Arg-Phe-Gln-Trp-Gln-Phe
      Glu-Gln-Gln-NH(2)), by fluorescence, infrared spectroscopy, and hydrogen
      deuterium exchange. Like Abeta(1-40), the peptide is toxic, and conditions which
      produce intermediate oligomers show higher toxicity against cells than either
      monomeric forms or higher aggregates of the peptide. Further, P(11-2) also binds
      to both zwitterionic (POPC) and negatively charged (POPC:POPG) liposomes,
      acquires a partial beta-sheet conformation in presence of lipid, and is protected
      against deuterium exchange in the presence of lipids. The results show that a
      simple rationally designed model beta-sheet peptide recapitulates many important
      features of Abeta peptide structure and function, reinforcing the idea that
      toxicity arises, at least in part, from a common mode of action on membranes that
      is independent of specific aspects of the amino acid sequence. Further studies of
      such well-behaved model peptide systems will facilitate the investigation of the
      general principles that govern the molecular interactions of aggregation-prone
      disease-associated peptides with cell and/or membrane surfaces.

PMID- 19393617
TI  - PinX1 is recruited to the mitotic chromosome periphery by Nucleolin and
      facilitates chromosome congression.
AB  - Mitotic chromosome movements are orchestrated by interactions between spindle
      microtubules and chromosomes. It is well known that kinetochore is the major site
      where microtubule-chromosome attachment occurs. However, the functions of other
      domains of chromosome such as chromosome periphery have remained elusive. Our
      previous studies show that PinX1 distributes to chromosome periphery and
      kinetochore during mitosis, and harbors the microtubule binding activity. Here we
      report that PinX1 interacts with Nucleolin, a chromosome periphery protein,
      through its C-termini. Deconvolution microscopic analyses show PinX1 mainly co
      localizes with Nucleolin at chromosome periphery in prometaphase. Moreover,
      depletion of Nucleolin abolishes chromosome periphery localizations of PinX1,
      suggesting a functional interrelationship between PinX1 and Nucleolin.
      Importantly, repression of PinX1 and Nucleolin abrogates chromosome segregation
      in real-time mitosis, validating the functional importance of PinX1-Nucleolin
      interaction. We propose PinX1 is recruited to chromosome periphery by Nucleolin
      and a complex of PinX1 and Nucleolin is essential for faithful chromosome
      congression.

PMID- 19393618
TI  - Engineering a versatile tandem repeat-type alpha2-6sialic acid-binding lectin.
AB  - Previously, we developed an alpha2-6-sialic acid (Sia)-specific lectin (SRC)
      starting from an R-type galactose-specific lectin C-terminal domain. However, it
      showed relatively low affinity because of its monovalency. Here, we engineered a
      tandem repeat construct (SRC2) showing substantial affinity for alpha2,6
      sialylated N-glycans (in the order of 10(-6)M in K(d)), almost comparable to a
      natural alpha2-6Sia-specific lectin from Sambucus sieboldiana (SSA). Notably, its
      binding to branched N-glycans was found to be more selective than SSA.
      Nevertheless, SRC2 showed no apparent hemagglutinating activity, while it exerted
      strong erythrocyte-binding activity. This unique feature will help flow cytometry
      analysis, where usual lectins including SSA agglutinate cells. Some other
      biochemical properties investigated for SRC2, e.g., high productivity in bacteria
      and easy release of captured glycoproteins with lactose have demonstrated
      versatility of this mutant protein as a powerful tool for sialoglycomics.

PMID- 19393616
TI  - Combinatorial morphogenesis of dendritic spines and filopodia by SPAR and alpha
      actinin2.
AB  - Rap small GTPases regulate excitatory synaptic strength and morphological
      plasticity of dendritic spines. Changes in spine structure are mediated by the F
      actin cytoskeleton, but the link between Rap activity and actin dynamics is
      unclear. Here, we report a novel interaction between SPAR, a postsynaptic
      inhibitor of Rap, and alpha-actinin, a family of actin-cross-linking proteins.
      SPAR and alpha-actinin engage in bidirectional structural plasticity of dendritic
      spines: SPAR promotes spine head enlargement, whereas increased alpha-actinin2
      expression favors dendritic spine elongation and thinning. Surprisingly, SPAR and
      alpha-actinin2 can function in an additive rather than antagonistic fashion at
      the same dendritic spine, generating combination spine/filopodia hybrids. These
      data identify a molecular pathway bridging the actin cytoskeleton and Rap at
      synapses, and suggest that formation of spines and filopodia are not necessarily
      opposing forms of structural plasticity.

PMID- 19393619
TI  - Peroxynitrite-induced p38 MAPK pro-apoptotic signaling in enterocytes.
AB  - Enterocyte apoptosis in necrotizing enterocolitis is partly due to the
      elaboration of toxic intermediates of nitric oxide (NO), such as peroxynitrite
      (PN). Because p38 mitogen-activated protein kinase (MAPK) and serine-threonine
      kinase (AKT) are well-characterized pro- and anti-apoptotic mediators,
      respectively, we hypothesized that PN could induce enterocyte apoptosis via
      activation of p38 and deactivation of AKT. To test this hypothesis, the rat
      intestinal cell line, IEC-6, was treated with PN. PN caused phosphorylation of
      p38, its upstream activator, MKK3/6, and downstream effector, transcription
      factor ATF-2. PN-induced apoptosis was inhibited by the p38 inhibitor, SB202190,
      and by p38 siRNA. PN decreased AKT phosphorylation; this effect was abrogated by
      pre-treatment with SB202190 or p38 siRNA. PN exposure also increased the activity
      of the protein phosphatase 2A (PP2A). These data demonstrate that PN-mediated
      apoptosis depends on the p38 pathway and that p38 mediates deactivation of AKT
      survival pathways possibly by the involvement of PP2A.

PMID- 19393620
TI  - Generation of an ABCG2(GFPn-puro) transgenic line--a tool to study ABCG2
      expression in mice.
AB  - The ATP-binding cassette (ABC) transporter 2 (ABCG2) is expressed by stem cells
      in many organs and in stem cells of solid tumors. These cells are isolated based
      on the side population (SP) phenotype, a Hoechst 3342 dye efflux property
      believed to be conferred by ABCG2. Because of the limitations of this approach we
      generated transgenic mice that express Nuclear GFP (GFPn) coupled to the
      Puromycin-resistance gene, under the control of ABCG2 promoter/enhancer
      sequences. We show that ABCG2 is expressed in neural progenitors of the
      developing forebrain and spinal cord and in embryonic and adult endothelial cells
      of the brain. Using the neurosphere assay, we isolated tripotent ABCG2-expressing
      neural stem cells from embryonic mouse brain. This transgenic line is a powerful
      tool for studying the expression of ABCG2 in many tissues and for performing
      functional studies in different experimental settings.

PMID- 19393621
TI  - IL-33, a recently identified interleukin-1 gene family member, is expressed in
      human adipocytes.
AB  - Inflammation occurs in adipose tissue in obesity. We have examined whether IL-33,
      a recently identified IL-1 gene family member, and its associated receptors are
      expressed in human adipocytes. IL-33, IL-1RL1 and IL-1RAP gene expression was
      observed in human visceral white fat, in preadipocytes and in adipocytes (SGBS
      cells). Treatment with TNFalpha for 24h induced a 6-fold increase in IL-33 mRNA
      level in preadipocytes and adipocytes. Time-course studies with adipocytes showed
      that the increase in IL-33 mRNA with TNFalpha was maximal (>55-fold) at 12h. This
      response was markedly different to IL-1beta (peak mRNA increase at 2h; 5.4-fold)
      and 1L-18 (peak mRNA increase at 6h; >1500-fold). Exposure of adipocytes to
      hypoxia (1% O(2), 24h) did not alter IL-33 mRNA level; in preadipocytes, however,
      there was a 3-fold increase. Human adipocytes and preadipocytes express IL-33,
      but the various IL-1 family members exhibit major differences in responsiveness
      to TNFalpha.

PMID- 19393622
TI  - Calmodulin-dependent kinase II regulates Dlx5 during osteoblast differentiation.
AB  - Calmodulin-dependent kinase II (CaMKII) acts as a key regulator of osteoblast
      differentiation. CaMKII is a Ca(2+)-activated serine/threonine kinase and it
      regulates the activity of target proteins by phosphorylation. Dlx5 transcription
      factor plays crucial roles in osteoblast differentiation. The expression of Dlx5
      is regulated by several osteogenic signaling pathways from early stages of
      osteoblastogenesis. In addition, Dlx5 can be phosphorylated and activated by p38,
      suggesting that the function of Dlx5 can be also modulated by post-translational
      modification. Although CaMKII and Dlx5 both play crucial roles during osteoblast
      differentiation, the interaction between CaMKII and Dlx5 has not been
      investigated. In the current study, we examined the effects CamKII on the
      function of Dlx5. We found that CaMKII phosphorylates Dlx5, and that CaMKII
      increases the protein stability and the osteoblastogenic transactivation activity
      of Dlx5. Conversely, a CaMKII inhibitor KN-93 decreased the osteogenic and
      transactivation activities of Dlx5. These results indicate that CaMKII regulates
      osteoblast differentiation, at least in part, by increasing the protein stability
      and the transcriptional activity of Dlx5.

PMID- 19393623
TI  - Endothelin promotes neurite elongation by a mechanism dependent on c-Jun N
      terminal kinase.
AB  - Endothelin (ET), which is known as a vasoconstrictive peptide, is associated with
      a lot of biological functions. Although endothelin receptors are expressed in the
      central nervous system (CNS), little is known about the effects of endothelin on
      neuronal function. In this study, we reported that endothelins elongate cortical
      neurites via the endothelin A receptor. All the endothelin isoforms tested,
      endothelin-1, endothelin-2, and endothelin-3, promoted neurite elongation. ET-1
      induced neurite elongation was specifically inhibited by treatment with BQ123, an
      antagonist for the endothelin A receptor. In addition, inhibition of ET-1-induced
      c-Jun N-terminal kinase (JNK) activation by treatment with SP600125, a JNK
      inhibitor, also prevented the ET-1-mediated promotion of neurite elongation.
      Thus, endothelin induces cortical neurite elongation through the endothelin A
      receptor by a mechanism dependent on JNK.

PMID- 19393624
TI  - Relationship between calcium release and NADPH oxidase inhibition in human
      neutrophils.
AB  - The aim of this study was to investigate the possible relationship between NADPH
      oxidase activity and changes in cytosolic Ca(2+) in response to different
      agonists. Treatment of neutrophils with leukotriene B4 (LTB(4)) demonstrated
      characteristic changes to cytoslic Ca(2+) yielding an EC(50) of 4nM. The pA(2)
      values for the specific LTB(4) receptor (BLT) antagonists, U-75302 and LY-255283
      were 6.32 and 6.38, respectively. Similarly, neutrophils treated with N-formyl-l
      methionyl-l-leucyl-l-phenylalanine (FMLP) and platelet activating factor (PAF)
      exhibited changes in cytoslic Ca(2+) in a dose dependant manner with pD(2) values
      of 9.0 and 9.9, respectively. The phorbol ester PMA prevented elevations in
      cytosolic Ca(2+) in response to LTB(4), FMLP and PAF with IC(50) values of 5.88,
      1.44 and 5.71nM, respectively. In addition, potent NADPH oxidase inhibitors
      apocynin and diphenyleneiodonium (DPI) inhibited FMLP mediated cytosolic Ca(2+)
      release. These results demonstrate that inhibition of the NADPH oxidase
      suppresses cytosolic Ca(2+) release in FMLP activated human neutrophils.

PMID- 19393625
TI  - Metabolism of 1alpha,25-dihydroxyvitamin D2 by human CYP24A1.
AB  - The metabolism of 1alpha,25-dihydroxyvitamin D2 (1alpha,25(OH)2D2) by human
      CYP24A1 was examined using the recombinant enzyme expressed in Escherichia coli
      cells. HPLC analysis revealed that human CYP24A1 produces at least 10
      metabolites, while rat CYP24A1 produces only three metabolites, indicating a
      remarkable species-based difference in the CYP24A1-dependent metabolism of
      1alpha,25(OH)2D2 between humans and rats. LC-MS analysis and periodate treatment
      of the metabolites strongly suggest that human CYP24A1 converts 1alpha,25(OH)2D2
      to 1alpha,24,25,26(OH)4D2, 1alpha,24,25,28(OH)4D2, and 24-oxo-25,26,27-trinor
      1alpha(OH)D2 via 1alpha,24,25(OH)3D2. These results indicate that human CYP24A1
      catalyzes the C24-C25 bond cleavage of 1alpha,24,25(OH)2D2, which is quite
      effective in the inactivation of the active form of vitamin D2. The combination
      of hydroxylation at multiple sites and C-C bond cleavage could form a large
      number of metabolites. Our findings appear to be useful to predict the metabolism
      of vitamin D2 and its analogs in the human body.

PMID- 19393626
TI  - Characterization of recombinant human cementum protein 1 (hrCEMP1): primary role
      in biomineralization.
AB  - Cementum protein 1 (CEMP1) has been recently cloned, and in vitro experiments
      have shown functions as regulator of cementoblast behavior and inducer of
      differentiation of non-osteogenic cells toward a cementoblastic/osteoblastic
      phenotype. In this study, we have produced a full-length human recombinant CEMP1
      protein in a human gingival fibroblast cell line. The purified protein (hrCEMP1)
      has a M(r) 50,000. Characterization of hrCEMP1 indicates that its secondary
      structure is mainly composed of beta-sheet (55%), where random coil and alpha
      helix conformations correspond to 35% and 10%, respectively. It was found that
      hrCEMP1 is N-glycosylated, phosphorylated and possesses strong affinity for
      hydroxyapatite. Even more important, our results show that hrCEMP1 plays a role
      during the biomineralization process by promoting octacalcium phosphate (OCP)
      crystal nucleation. These features make CEMP1 a very good candidate for
      biotechnological applications in order to achieve cementum and/or bone
      regeneration.

PMID- 19393627
TI  - STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated STAT3
      activation.
AB  - Signal transducing adaptor protein-2 (STAP-2) is a recently identified adaptor
      protein that contains Pleckstrin and Src homology 2 (SH2)-like domains as well as
      a YXXQ motif in its C-terminal region. STAP-2 is also known as breast tumor
      kinase (Brk) substrate (BKS). Our previous studies revealed that STAP-2 binds to
      signal transducer and activator of transcription 3 (STAT3) and STAT5, and
      regulates the signaling pathways downstream of them. In the present study, we
      identified tyrosine-250 (Tyr250) in STAP-2 as a major site of phosphorylation by
      Brk, using a series of STAP-2 YF mutants and anti-phospho-STAP-2 Tyr250 antibody.
      Furthermore, overexpression of the STAP-2 Y250F mutant protein affected Brk
      mediated STAT3 activation. Importantly, small-interfering RNA-mediated reduction
      of endogenous STAP-2 expression decreased Brk-mediated STAT3 activation. Taken
      together, our findings demonstrate that STAP-2 is phosphorylated at Tyr250 by
      Brk, and plays an important role in Brk-mediated STAT3 activation.

PMID- 19393628
TI  - Visfatin causes endothelium-dependent relaxation in isolated blood vessels.
AB  - Visfatin is a novel adipocyte-derived cytokine. We hypothesized that visfatin
      could directly affect vascular reactivity. To test the hypothesis, effects of
      visfatin on contraction of isolated blood vessels were examined. In endothelium
      intact rat aorta, pretreatment with visfatin (100 ng/ml, 30 min) inhibited
      noradrenaline (NA; 1 nM-1 microM)-induced contraction. In NA (100 nM)-pre
      contracted aorta, visfatin (1-100 ng/ml) directly induced a relaxation. Although
      an N(G)-Nitro-L-arginine methyl ester (300 microM, 15 min) inhibited the
      relaxation, an insulin receptor inhibitor, AGL2263 (10 microM, 20 min) was
      ineffective. Visfatin (100 ng/ml, 20 min) induced a phosphorylation of eNOS at
      serine 1177 and a de-phosphorylation of eNOS at threonine 495. Visfatin also
      induced a phosphorylation of Akt at serine 473 and a substrate of cGMP-dependent
      protein kinase, vasodilator stimulated phosphoprotein at serine 239. Present
      study revealed for the first time that visfatin has a vasodilating effect on
      isolated blood vessels, which is mediated via endothelium-derived NO.

PMID- 19393629
TI  - 1,25-Dihydroxyvitamin D3 induces Ca2+-mediated apoptosis in adipocytes via
      activation of calpain and caspase-12.
AB  - Induction of apoptotic cell death is emerging as a promising strategy for
      prevention and treatment of obesity because removing of adipocytes via apoptosis
      may result in reducing body fat and a long-lasting maintenance of weight loss.
      However, the mechanisms controlling adipocyte apoptosis are unknown and even the
      ability of adipocytes to undergo apoptosis has not been conclusively
      demonstrated. We have shown previously that the specific Ca(2+) signal, sustained
      increase in intracellular Ca(2+), triggers apoptotic cell death via activation of
      Ca(2+)-dependent proteases and that the apoptosis-inducing effect of the hormone
      1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is mediated through Ca(2+)
      signaling. Here, we report that 1,25(OH)(2)D(3) induces apoptosis in mature mouse
      3T3-L1 adipocytes via activation of Ca(2+)-dependent calpain and Ca(2+)/calpain
      dependent caspase-12. Treatment of adipocytes with 1,25(OH)(2)D(3) induced, in
      concentration- and time-dependent fashion, a sustained increase in the basal
      level of intracellular Ca(2+). The increase in Ca(2+) was associated with
      induction of apoptosis and activation of mu-calpain and caspase-12. Our results
      demonstrate that Ca(2+)-mediated apoptosis can be induced in mature adipocytes
      and that the apoptotic molecular targets activated by 1,25(OH)(2)D(3) in these
      cells are Ca(2+)-dependent calpain and caspase-12. These findings provide
      rationale for evaluating the role of vitamin D in prevention and treatment of
      obesity.

PMID- 19393630
TI  - Conformational detection of p53's oligomeric state by FlAsH Fluorescence.
AB  - The p53 tumor suppressor protein is a critical checkpoint in prevention of tumor
      formation, and the function of p53 is dependent on proper formation of the active
      tetramer. In vitro studies have shown that p53 binds DNA most efficiently as a
      tetramer, though inactive p53 is predicted to be monomeric in vivo. We
      demonstrate that FlAsH binding can be used to distinguish between oligomeric
      states of p53, providing a potential tool to explore p53 oligomerization in vivo.
      The FlAsH tetra-cysteine binding motif has been incorporated along the dimer and
      tetramer interfaces in the p53 tetramerization domain to create reporters for the
      dimeric and tetrameric states of p53, though the geometry of the four cysteines
      is critical for efficient FlAsH binding. Furthermore, we demonstrate that FlAsH
      binding can be used to monitor tetramer formation in real-time. These results
      demonstrate the potential for using FlAsH fluorescence to monitor protein-protein
      interactions in vivo.

PMID- 19393631
TI  - The actin cytoskeleton in meiotic maturation and fertilization of starfish eggs.

PMID- 19393632
TI  - CLC-7: a potential therapeutic target for the treatment of osteoporosis and
      neurodegeneration.
AB  - CLC-7 is a member of the voltage-gated chloride channels family. It resides
      mainly in the late endosomes, lysosomes and the ruffled membrane of osteoclasts.
      Mice deficient in the ubiquitously expressed ClC-7 Cl(-) channel show severe
      osteopetrosis and retinal degeneration. In the present review, some of the known
      features of CLC-7 such as structure, function and its roles in physiological or
      pathophysiological processes are highlighted.

PMID- 19393633
TI  - Reduced glutathione is highly expressed in white matter and neurons in the
      unperturbed mouse brain--implications for oxidative stress associated with
      neurodegeneration.
AB  - Oxidative stress is implicated in the pathogenesis of many neurodegenerative
      diseases, including Parkinson's disease and Alzheimer's disease. The depletion of
      glutathione (GSH) a powerful antioxidant renders cells particularly vulnerable to
      oxidative stress. Isolated neuronal and glial cell culture studies suggest that
      glia rather than neurons have greatest reserves of GSH, implying that neurons are
      most sensitive to oxidative stress. However, pathological in vivo studies suggest
      that GSH associated enzymes are elevated in neurons rather than astrocytes. The
      active, reduced form of GSH is rapidly degraded thus making it difficult to
      identify the location of GSH in post-mortem tissue. Therefore, to determine
      whether GSH is more highly expressed in neurons or astrocytes we perfused mouse
      brains with a solution containing NEM which reacts with the sulfhydryl group of
      GSH, thus locking the active form in situ, prior to immunostaining with an anti
      GS-NEM antibody. We obtained brightfield and fluorescent digital images of
      sections stained with DAPI and antibodies directed against GS-NEM, glial
      fibrillary acidic protein (GFAP) in regions containing the hippocampus, striatum,
      frontal cortex, midbrain nuclei, cerebellum and reticular formation neurons. GSH
      was most abundant in neurons and white matter in all brain regions, and only in
      occasional astrocytes lining the third and fourth ventricles. High levels of GSH
      in neurons and white matter, suggests astrocytes rather than neurons may be
      particularly vulnerable to oxidative stress.

PMID- 19393634
TI  - Decreased expression of multidrug efflux transporters in the brains of GSK-3beta
      transgenic mice.
AB  - Multidrug efflux transporters protect cells in the brain from potentially harmful
      substances but also from therapeutically useful drugs. Thus any condition that
      causes changes in their expression is of some importance with regard to drug
      access. In this study, changes in efflux transporter expression are investigated
      in mice containing a mutant constitutively active glycogen synthase kinase-3 (GSK
      3beta) transgene, driven by the Thy-1 promoter so limiting its localization
      predominantly to neurons and some glial cells. As expected, decreases in beta
      catenin were evident via Western blot analyses of cortical homogenates prepared
      from brains of these transgenic mice. As assessed by real time qRT-PCR, decreased
      transcript levels of the mdr1b isoform of P-glycoprotein, Mrp1 and Mrp4,
      (transporters associated with neurons and/or glial cells) were observed in the
      cortex but not the subventricular zone or hippocampus of the transgenic compared
      to wild type mouse brains. By contrast, no such decreases were evident with the
      mdr1a isoform of P-glycoprotein and Bcrp, transporters predominantly found in
      brain endothelium. Such transporter expression changes could not be accounted for
      by alterations in blood vessel density or neuronal to glial cell ratios as
      analyzed both from immunocytochemical staining and from RT-PCR. These
      observations support previous in vitro data showing that manipulations to GSK
      3beta activity that alter signaling via beta-catenin can influence the expression
      of efflux transporters. Implications from this are that drug distribution into
      cells within the brain of these transgenic mice could be enhanced, hence
      warranting further investigation.

PMID- 19393636
TI  - Determination of functionally essential neuronal population of the olfactory
      epithelium for nipple search and subsequent suckling behavior in newborn rats.
AB  - Neuronal population of the olfactory epithelium required for nipple search and
      subsequent suckling behavior was examined in newborn rats. After unilateral
      ablation of the olfactory bulb, different concentrations of ZnSO(4) were
      contralaterally injected into the nasal cavity to produce varying degrees of
      neuronal degeneration in the olfactory epithelium. The ZnSO(4)-treatment resulted
      in two populations of pups. One exhibited suckling while the other did not, and
      intact olfactory receptor neurons were quantified immunohistochemically using an
      antibody for olfactory marker protein (OMP), a marker protein for olfactory
      receptor neurons. The total numbers of the OMP (+) cells in the ZnSO(4)-treated
      pups with suckling capability ranged between 2457 and 4615, whereas those in the
      ZnSO(4)-treated pups without suckling capability ranged between 112 and 2398.
      With the mean value (4969) of the total numbers of the OMP (+) cells of the
      normal/control pups assumed to represent 100%, the total numbers of the OMP (+)
      cells accounted for 49-93% in the suckling (+) group and 2-48% in the suckling (
      ) group. From these findings, we conclude that approximately 50% of neuronal
      population of the olfactory epithelium is a critical value to distinguish between
      the two groups with and without suckling capability in the unilateral olfactory
      system of newborn rats.

PMID- 19393635
TI  - A neuronal VLDLR variant lacking the third complement-type repeat exhibits high
      capacity binding of apoE containing lipoproteins.
AB  - Very-low-density lipoprotein receptor (VLDLR) is a multi ligand apolipoprotein E
      (apoE) receptor and is involved in brain development through Reelin signaling.
      Different forms of VLDLR can be generated by alternative splicing. VLDLR-I
      contains all exons. VLDLR-II lacks an O-linked sugar domain encoded by exon 16,
      while VLDLR-III lacks the third complement-type repeat in the ligand binding
      domain encoded by exon 4. We quantitatively compared lipoprotein binding to human
      VLDLR variants and analyzed their mRNA expression in both human cerebellum and
      mouse brain. VLDLR-III exhibited the highest capacity in binding to apoE enriched
      beta-VLDL in vitro and was more effective in removing apoE containing
      lipoproteins from the circulation than other variants in vivo. In human
      cerebellum, the major species was VLDLR-II, while the second most abundant
      species was a newly identified VLDLR-IV which lacks both exon 4 and 16. VLDLR-I
      was present at low levels. In adult mice, exon 4 skipping varied between 30 and
      47% in different brain regions, while exon 16 skipping ranged by 51-76%.
      Significantly higher levels of VLDLR proteins were found in mouse cerebellum and
      cerebral cortex than other regions. The deletions of exon 4 and exon 16
      frequently occurred in primary neurons, indicating that newly identified variant
      VLDLR-IV is abundant in neurons. In contrast, VLDLR mRNA lacking exon 4 was not
      detectable in primary astrocytes. Such cell type-specific splicing patterns were
      found in both mouse cerebellum and cerebral cortex. These results suggest that a
      VLDLR variant lacking the third complement-type repeat is generated by neuron
      specific alternative splicing. Such differential splicing may result in different
      lipid uptake in neurons and astrocytes.

PMID- 19393637
TI  - Hypoglycemic and antioxidant effects of phenolic extracts and purified
      hydroxytyrosol from olive mill waste in vitro and in rats.
AB  - This study aimed to evaluate the effect of phenolic extract and purified
      hydroxytyrosol (HT) from olive mill waste (OMW) on oxidative stress and
      hyperglycemia in alloxan-induced diabetic rats. The OMW biophenols were extracted
      using ethyl acetate. The obtained extract was fractionated by solid phase
      extraction (SPE) experimentation to generate two fractions: (F1) and (F2). HPLC
      UV and HPLC-MS analysis showed that (F1) was made of known OMW monomeric
      phenolics mainly hydroxytyrosol (HT) while (F2) contained oligomeric and
      polymeric phenols such as verbascosid and ligstrosid. (HT) was purified from (F1)
      using silica gel-column chromatography and silica gel-TLC techniques. In
      incubated pancreas, supplementation of OMW fractions enhanced insulin secretion.
      The administration of OMW extract fractions (F1) and (F2) as well as purified
      (HT) in diabetic rats caused a decrease in glucose level in plasma and an
      increase in renal superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GPX) activities in liver and kidney. Furthermore, a protective action
      against hepatic and renal toxicity in diabetic rats was clearly observed.
      Furthermore, a significant decrease in hepatic and renal indices toxicity was
      observed, i.e. alkalines phosphatases (ALP), aspartate and lactate transaminases
      (AST and ALT) activities and the thiobarbituric acid-reactive substances (TBARs),
      total and direct bilirubin, creatinine and urea levels. In addition, (F1), (F2)
      and especially (HT) decreased triglycerides (TG), total-cholesterol (T-Ch) and
      higher HDL-cholesterol (HDL-Ch) in serum. These beneficial effects of OMW
      biophenols were confirmed by histological findings in hepatic, renal and
      pancreatic tissues of diabetic rats. This study demonstrates for the first time
      that OMW polyphenols and especially (HT) are efficient in inhibiting
      hyperglycemia and oxidative stress induced by diabetes and suggests that
      administration of HT may be helpful in the prevention of diabetic complications
      associated with oxidative stress.

PMID- 19393638
TI  - Point-of-care fluorescence immunoassay for prostate specific antigen.
AB  - BACKGROUND: Prostate specific antigen (PSA) is widely used as a clinical marker
      for diagnosis, screening, and prognosis of prostate cancer. A fluorescence (FL)
      dye-incorporated immunochromatographic assay (ICA) was developed for detection of
      PSA concentration in whole blood or serum. METHODS: Whole blood or serum mixed
      with FL-conjugated detector was loaded onto a cartridge and incubated for 12 min.
      The FL intensity of the cartridge was then measured in a laser FL scanner. The
      analytical performance of the FL-ICA system was evaluated by precision and
      recovery tests. The comparability of the new method was examined with an
      automated analyzer. RESULTS: A reliable correlation between area ratio (AT/AC),
      reflecting FL intensity of test/control line, and PSA concentration was observed
      (r=0.998). The CVs of intra- and inter-assay precision in a range of 2.5-8
      microg/l were <6.0% and 4.5%, respectively, and analytical recovery of the FL-ICA
      system fell within 6.5% at the tested samples. When the FL-ICA method was
      compared with Abbott AxSYM and Bayer Centaur analyzers, there were strong
      correlations (r=0.993 and r=0.992, p<0.0001). CONCLUSION: The FL-ICA system with
      point-of-care-testing (POCT) appeared to be an easy, fast and suitable method for
      measurement of PSA concentration in whole blood, and needs no accessory equipment
      to separate serum.

PMID- 19393639
TI  - Human saliva cortisone and cortisol simultaneous analysis using reverse phase
      HPLC technique.
AB  - BACKGROUND: Hyper-hypo tension (like Cushing's syndrome, apparent
      mineralocorticoid excess syndrome and Addison's disease) diagnostic laboratory
      requires cortisol (F) analysis. The simultaneous analysis of human saliva F and
      cortisone (E), the inactive F metabolite, by solid phase extraction and RP-HPLC
      was studied. METHODS: Saliva/standard samples were C18-SPE extracted, dried and
      resuspended. E and F were analysed by isocratic RP-HPLC (acetonitrile/water
      27/73%) and UV detection. In the morning and in the evening Salivette stimulated
      saliva specimens were collected from healthy volunteers. RESULTS: The E and F
      calibration curve ranges were 11.0-110.0 and 5.5-55.0 nmol/l respectively. The
      LOD was 0.2 and 0.1 nmol/l for E and F respectively. The intra and inter assay
      CVs were respectively 2.7-6.6 and 5.6-7.0% for E and 5.8-7.0 and 11.7-13.1% for
      F. The E and F spiked saliva sample recovery was 99% and 88% respectively. Saliva
      specimen stability was validated. E and F saliva levels in healthy volunteers
      were significantly (p<0.001) higher at 8 a.m. compared with 11 p.m. (26.4+/-8.9
      vs. 4.3+/-2.9 nmol/l for E; 11.1+/-4.0 vs. 2.5+/-1.5 nmol/l for F, respectively).
      CONCLUSIONS: This method is suitable for periodic analyses in a clinical
      biochemistry laboratory for endocrinology investigation purposes, simultaneously
      analysing E and F levels in a saliva specimen.

PMID- 19393641
TI  - A reverse genetic screen in the zebrafish identifies crb2b as a regulator of the
      glomerular filtration barrier.
AB  - The glomerular filtration barrier is necessary for the selective passage of low
      molecular weight waste products and the retention of blood plasma proteins.
      Damage to the filter results in proteinuria. The filtration barrier is the major
      pathogenic site in almost all glomerular diseases and its study is therefore of
      clinical significance. We have taken advantage of the zebrafish pronephros as a
      system for studying glomerular filtration. In order to identify new regulators of
      filtration barrier assembly, we have performed a reverse genetic screen in the
      zebrafish testing a group of genes which are enriched in their expression within
      the mammalian glomerulus. In this novel screen, we have coupled gene knockdown
      using morpholinos with a physiological glomerular dye filtration assay to test
      for selective glomerular permeability in living zebrafish larvae. Screening 20
      genes resulted in the identification of ralgps1, rapgef2, rabgef1, and crb2b. The
      crumbs (crb) genes encode a family of evolutionarily conserved proteins important
      for apical-basal polarity within epithelia. The crb2b gene is expressed in
      zebrafish podocytes. Electron microscopic analysis of crb2b morphants reveals a
      gross disorganization of podocyte foot process architecture and loss of slit
      diaphragms while overall polarity is maintained. Nephrin, a major component of
      the slit diaphragm, is apically mis-localized in podocytes from crb2b morphants
      suggesting that crb2b is required for the proper protein trafficking of Nephrin.
      This report is the first to show a role for crb function in podocyte
      differentiation. Furthermore, these results suggest a novel link between
      epithelial polarization and the maintenance of a functional filtration barrier.

PMID- 19393640
TI  - Hedgehog signaling patterns mesoderm in the sea urchin.
AB  - The Hedgehog (Hh) signaling pathway is essential for patterning many structures
      in vertebrates including the nervous system, chordamesoderm, limb and endodermal
      organs. In the sea urchin, a basal deuterostome, Hh signaling is shown to
      participate in organizing the mesoderm. At gastrulation the Hh ligand is
      expressed by the endoderm downstream of the Brachyury and FoxA transcription
      factors in the endomesoderm gene regulatory network. The co-receptors Patched
      (Ptc) and Smoothened (Smo) are expressed by the neighboring skeletogenic and non
      skeletogenic mesoderm. Perturbations of Hh, Ptc and Smo cause embryos to develop
      with skeletal defects and inappropriate non-skeletogenic mesoderm patterning,
      although initial specification of mesoderm occurs without detectable
      abnormalities. Perturbations of the pathway caused late defects in skeletogenesis
      and in the non-skeletogenic mesoderm, including altered numbers of pigment and
      blastocoelar cells, randomized left-right asymmetry of coelomic pouches, and
      disorganized circumesophageal muscle causing an inability to swallow. Together
      the data support the requirement of Hh signaling in patterning each of the
      mesoderm subtypes in the sea urchin embryo.

PMID- 19393642
TI  - Diabetes modulates capacitative calcium entry and expression of transient
      receptor potential canonical channels in human saphenous vein.
AB  - Diabetes is associated with a perturbation of signaling pathways in vascular
      tissue, which causes vasomotor dysfunction such as hypertension. We have
      previously demonstrated that vessels from diabetic patients were more contractile
      than those from non-diabetic. However, in human vessels, the receptor-stimulated
      contraction is mainly due to enzymatic, rather than calcium signaling pathway. In
      this study, we hypothesized that the differential contractile response between
      diabetic and non-diabetic human vessels could be due to the receptor signaling to
      sarcoplasmic reticulum and the regulation of capacitative calcium entry. In
      saphenous vein samples (n=20) collected from diabetic patients undergoing bypass
      surgery, the contraction initiated by the addition of the sarco-endoplasmatic
      reticulum calcium ATPase blocker, cyclopiazonic acid, was significantly higher
      than that in the vessels from non-diabetic patients (n=26) (84.0+/-14.9% vs
      44.2+/-9.2%), and this contraction was inhibited by SKF-96365, an inhibitor of
      store-operated calcium channels. Pre-incubation with indomethacin reduced the
      cyclopiazonic acid-induced contraction in the non-diabetic veins, but had no
      effect on the diabetic ones. The gene expression of transient receptor potential
      canonical channels (TRPC)4 was upregulated by 22% in the diabetic vessels
      compared with the non-diabetic ones. However, the protein expression of TRPC1 and
      TRPC6 was downregulated in the diabetic group by 50%. We concluded that diabetes
      would modulate the capacitative calcium entry likely through the store-operated
      calcium channel specifically via the regulation of TRPC.

PMID- 19393643
TI  - B vitamins alleviate indices of neuropathic pain in diabetic rats.
AB  - There are sporadic reports that assorted combinations of B vitamins can alleviate
      pain in diabetic patients, but there is neither agreement on the relative
      efficacy of individual B vitamins nor understanding of the mechanisms involved.
      We therefore investigated the efficacy of a cocktail of the vitamins B1, B6 and
      B12 in alleviating behavioral indices of sensory dysfunction such as allodynia
      and hyperalgesia in diabetic rats and also the relative contribution of
      individual components of the cocktail. Repeated daily treatment with the cocktail
      of B vitamins for 7-9 days ameliorated tactile allodynia and formalin-evoked
      hyperalgesia in a dose-dependent manner and also improved sensory nerve
      conduction velocity in diabetic rats. Investigation of the contribution of
      individual B vitamins suggested that all three participated with variable
      efficacy in the alleviation of allodynia after protracted, but not single dose
      treatment. Only vitamin B6 improved sensory nerve conduction velocity slowing in
      diabetic rats when given alone. To address potential mechanisms of action, we
      measured markers of oxidative stress (lipid and protein oxidation) and
      inflammation (cyclooxygenase-2 (COX-2) and TNFalpha protein) in the nerve but
      treatment with the vitamin B cocktail did not significantly affect any of these
      parameters. The positive effects of B vitamins on functional and behavioral
      disorders of diabetic rats suggest a potential for use in treating painful
      diabetic neuropathy.

PMID- 19393644
TI  - Human papillomavirus in metastatic squamous carcinoma from unknown primaries in
      the head and neck: a retrospective 7 year study.
AB  - GOAL: Human Papillomavirus (HPV) is found to be increasingly implicated in head
      and neck cancers. The objective of this study was to determine the primary site
      of origin of HPV positive squamous carcinomas metastatic to lymph nodes of the
      neck. METHODS: Surgical pathology records from January 1, 2000 to July 31, 2007
      were used to identify surgically removed neck lymph nodes with the diagnosis of
      metastatic squamous carcinoma. Specimens in formalin-fixed, paraffin-embedded
      blocks were examined for HPV (+) by analyzing sequencing data generated by PCR
      and immunostaining for the expression of the p16INK biomarker, which is
      overexpressed if Rb is not present. H & E stained slides were also reviewed for
      histological classification. The available retrospective demographics were
      extracted from the charts to determine trends of confounding factors. RESULTS: Of
      the 43 patient samples, 41 contained adequate DNA to test for HPV. The mean age
      of the 41 patients was 62 years. All of the patients smoked and 39/41 patients
      consumed alcohol. The overall HPV (+) incident rate was 27% (11/41) by PCR with
      strongly diffuse or strong focal p16 staining. 9 of the 34 males and 2 of the 7
      females had HPV (+) carcinomas. The average age of the 2 HPV (+) females was 44,
      compared to the HPV (-) females who averaged 70. The average age of the HPV (+)
      males was 56 compared with the average age 55 of the HPV (-) males. HPV (+)
      carcinomas appeared to arise from multiple sites in the oropharynx, particularly
      the tonsils and tongues, including unknown primaries. By histological exam, most
      metastatic HPV(+) squamous carcinomas were poorly differentiated (basaloid)
      microscopically and grossly cystic. CONCLUSION: The 27% HPV (+) squamous cancers
      metastatic to neck lymph node originated from multiple sites in the oropharynx.
      The HPV (+) female population, although a total of only 2, tended to be much
      younger than the HPV (-) ones, whereas the HPV (+) male population was similar in
      age to the HPV (-) male population.

PMID- 19393645
TI  - Hepatocyte growth factor (HGF) signals through SHP2 to regulate primary mouse
      myoblast proliferation.
AB  - Niche localized HGF plays an integral role in G(0) exit and the return to mitotic
      activity of adult skeletal muscle satellite cells. HGF actions are regulated by
      MET initiated intracellular signaling events that include recruitment of SHP2, a
      protein tyrosine phosphatase. The importance of SHP2 in HGF-mediated signaling
      was examined in myoblasts and primary cultures of satellite cells. Myoblasts
      stably expressing SHP2 (23A2-SHP2) demonstrate increased proliferation rates by
      comparison to controls or myoblasts expressing a phosphatase-deficient SHP2 (23A2
      SHP2DN). By comparison to 23A2 myoblasts, treatment of 23A2-SHP2 cells with HGF
      does not further increase proliferation rates and 23A2-SHP2DN myoblasts are
      unresponsive to HGF. Importantly, the effects of SHP2 are independent of
      downstream ERK1/2 activity as inclusion of PD98059 does not blunt the HGF-induced
      proliferative response. SHP2 function was further evaluated in primary satellite
      cell cultures. Ectopic expression of SHP2 in satellite cells tends to decrease
      proliferation rates and siSHP2 causes an increase the percentage of dividing
      myogenic cells. Interestingly, treatment of satellite cells with high
      concentrations of HGF (50 ng/ml) inhibits proliferation, which can be overcome by
      knockdown of SHP2. From these results, we conclude that HGF signals through SHP2
      in myoblasts and satellite cells to directly alter proliferation rates.

PMID- 19393646
TI  - Behavioral abnormalities of fetal growth retardation model rats with reduced
      amounts of brain proteoglycans.
AB  - Fetal growth retardation (FGR) is a critical problem in the neonatal period,
      because a substantial population of infants born with FGR go on to develop
      various developmental disorders. In the present study, we produced FGR model rats
      by continuous administration of a synthetic thromboxane A2 analogue (STA2) to
      pregnant rats. The FGR pups exhibited a significant delay in postnatal
      neurological development. Moreover, behavioral analyses revealed the presence of
      a learning disability in juvenile FGR male rats. To investigate the mechanism
      underlying the neurological disorders, histological and biochemical analyses of
      the brain of FGR rats were performed. The density of neurons in the cortical
      plate of an FGR brain was low compared with the brains of a similarly aged,
      healthy rat. Consistent with this finding, the density of TUNEL-positive cells
      was higher in the cortical plate of FGR brains. Western blot analyses showed that
      the levels of three brain-specific chondroitin sulfate proteoglycans (CSPGs),
      neurocan, phosphacan, and neuroglycan C, were all significantly reduced in the
      brain of neonatal FGR rats compared with those of the control. The reduction of
      CSPG-levels and morphological changes in the brain may be relevant to
      neurological dysfunction in FGR.

PMID- 19393647
TI  - Selective vulnerability of adult cochlear nucleus neurons to de-afferentation by
      mechanical compression.
AB  - It is well established that the cochlear nucleus (CN) of developing species is
      susceptible to loss of synaptic connections from the auditory periphery. Less
      information is known about how de-afferentation affects the adult auditory
      system. We investigated the effects of de-afferentation to the adult CN by
      mechanical compression. This experimental model is quantifiable and highly
      reproducible. Five weeks after mechanical compression to the axons of the
      auditory neurons, the total number of neurons in the CN was evaluated using un
      biased stereological methods. A region-specific degeneration of neurons in the
      dorsal cochlear nucleus (DCN) and posteroventral cochlear nucleus (PVCN) by 50%
      was found. Degeneration of neurons in the anteroventral cochlear nucleus (AVCN)
      was not found. An imbalance between excitatory and inhibitory synaptic
      transmission after de-afferentation may have played a crucial role in the
      development of neuronal cell demise in the CN. The occurrence of a region
      specific loss of adult CN neurons illustrates the importance of evaluating all
      regions of the CN to investigate the effects of de-afferentation. Thus, this
      experimental model may be promising to obtain not only the basic knowledge on
      auditory nerve/CN degeneration but also the information relevant to the
      application of cochlear or auditory brainstem implants.

PMID- 19393648
TI  - Mitochondrial micro-calpain is not involved in the processing of apoptosis
      inducing factor.
AB  - Caspase-independent cell death, an important death pathway in many cells
      including neurons, is executed via apoptosis-inducing factor (AIF), an
      oxidoreductase, localized to the mitochondrial intermembrane space. AIF is
      processed and released from mitochondria following mitochondrial permeability
      transition pore (mPTP) formation, and translocates to the nucleus to induce DNA
      fragmentation and cell death. The release of AIF requires cleavage of its N
      terminus anchored in the inner mitochondrial membrane. The protease responsible
      for this AIF truncation has not been established, although there is considerable
      evidence suggesting a role for micro-calpain. We previously found that a pool of
      micro-calpain is localized to the mitochondrial intermembrane space, the
      submitochondrial compartment in which AIF truncation occurs. The close
      submitochondrial proximity of mitochondrial micro-calpain and AIF gives support
      to the hypothesis that mitochondrial micro-calpain may be the protease
      responsible for processing AIF prior to its release. In the present study, AIF
      was released from rat liver mitochondria following mPTP induction by
      atractyloside. This release was inhibited by the cysteine protease inhibitor
      MDL28170, but not by more specific calpain inhibitors PD150606 and calpastatin.
      Atractyloside caused swelling in rat brain mitochondria, but did not induce AIF
      release. In a mitochondrial fraction from SH-SY5Y neuroblastoma cells, incubation
      with 5 mM Ca(2+) resulted in the activation of micro-calpain but not in AIF
      truncation. In summary, the localization of micro-calpain to the mitochondrial
      intermembrane space is suggestive of its possible involvement in AIF processing,
      but direct experimental evidence supporting such a role has been elusive.

PMID- 19393649
TI  - The secreted Helicobacter cysteine-rich protein A causes adherence of human
      monocytes and differentiation into a macrophage-like phenotype.
AB  - Helicobacter pylori genomes typically contain 8 or 9 genes that code for secreted
      and highly disulfide-bridged proteins designated Helicobacter cysteine-rich
      proteins (Hcp). Here we show that HcpA (hp0211) but not HcpC (hp1098) triggers
      the differentiation of human myeloid Thp1 monocytes into macrophages. Small
      amounts of HcpA cause the transition of round-shaped monocytes into cells with
      star-like morphologies, adherence to the culture dish surface, phagocytosis of
      opsonized fluorescent microspheres, and expression of the surface marker protein
      CD11b, all of which are indicative of a macrophage-like phenotype. We conclude
      that HcpA acts as a bacterial immune modulator similar to a eukaryotic cytokine.

PMID- 19393650
TI  - Serum amyloid A and protein AA: molecular mechanisms of a transmissible
      amyloidosis.
AB  - Systemic AA-amyloidosis is a complication of chronic inflammatory diseases and
      the fibril protein AA derives from the acute phase reactant serum AA. AA
      amyloidosis can be induced in mice by an inflammatory challenge. The lag phase
      before amyloid develops can be dramatically shortened by administration of a
      small amount of amyloid fibrils. Systemic AA-amyloidosis is transmissible in mice
      and may be so in humans. Since transmission can cross species barriers it is
      possible that AA-amyloidosis can be induced by amyloid in food, e.g. foie gras.
      In mice, development of AA-amyloidosis can also be accelerated by other
      components with amyloid-like properties. A new possible risk factor may appear
      with synthetically made fibrils from short peptides, constructed for tissue
      repair.

PMID- 19393651
TI  - Essential role of p38 MAPK in caspase-independent, iPLA(2)-dependent cell death
      under hypoxia/low glucose conditions.
AB  - The mechanisms of cell death induced by hypoxia or ischemia are not yet fully
      understood. We have previously demonstrated that cell death induced by hypoxia
      occurs independently of caspases, and is mediated by phospholipase A(2) (PLA(2)).
      Here, we show that p38 mitogen-activated protein kinase is activated under
      hypoxia. A selective inhibitor of p38 or decrease in the p38alpha protein level
      prevents hypoxia-induced cell death. The p38 inhibitor abolishes PLA(2)
      activation by hypoxia, indicating that p38 acts upstream of PLA(2). The
      antioxidant N-acetyl-cysteine inhibits activation of p38 and cell death induced
      by hypoxia, indicating that reactive oxygen species (ROS) are responsible for p38
      activation. These results demonstrate that the ROS/p38/PLA(2) signaling axis has
      a crucial role in caspase-independent cell death induced by hypoxia.

PMID- 19393652
TI  - The role of molecular chaperones in human misfolding diseases.
AB  - Human misfolding diseases arise when proteins adopt non-native conformations that
      endow them with a tendency to aggregate and form intra- and/or extra-cellular
      deposits. Molecular chaperones, such as Hsp70 and TCP-1 Ring Complex
      (TRiC)/chaperonin containing TCP-1 (CCT), have been implicated as potent
      modulators of misfolding disease. These chaperones suppress toxicity of disease
      proteins and modify early events in the aggregation process in a cooperative and
      sequential manner reminiscent of their functions in de novo protein folding.
      Further understanding of the role of Hsp70, TRiC, and other chaperones in
      misfolding disease is likely to provide important insight into basic
      pathomechanistic principles that could potentially be exploited for therapeutic
      purposes.

PMID- 19393653
TI  - Evolution of environmental cue response mechanisms: adaptive variation in
      photorefractoriness.
AB  - Appropriate timing of transitions between annual cycle stages (reproduction,
      plumage molt, migration) is critical to fitness for birds living in temporally
      varying environments. Environmental cue response systems permit birds to
      orchestrate these transitions. This paper focuses on how photorefractoriness and
      one neuroendocrine correlate of it (GnRH system plasticity) have evolved to
      permit appropriate timing of the transition from breeding to plumage molt.
      Photorefractoriness is defined by two criteria. Criterion 1: photoinduced gonadal
      regression occurs without any decline in photoperiod. Criterion 2: photoinduced
      gonadal regression cannot be reversed by increased photoperiod, even continuous
      light. Through a comparative approach we show that: (1) Loss of Refractoriness
      Criterion 1 and of GnRH system down-regulation appear to represent adaptive
      specializations favoring highly temporally flexible or continuous breeding, (2)
      Refractoriness Criteria 1 and 2 are not always concordant, and Criterion 2 in
      particular is not well-correlated with degree of temporal reproductive
      flexibility, (3) occurrence of some cue response traits are better-explained by
      phylogenetic relationships among taxa than by current reproductive schedules
      (seasonal, flexible, opportunistic), (4) substantial temporal flexibility can be
      achieved in a variety of ways besides adaptive modifications of refractoriness,
      such as relaxation of long-day requirements for reproductive development, and
      enhancement of non-photic cue responsiveness. These comparisons also highlight
      fundamental similarities between some of the most opportunistic species and
      seasonal breeders, such as an autumn reproductive hiatus during molt. Even in the
      face of substantial environmental unpredictability, selection may often strongly
      favor regular scheduling of particularly critical life cycle stages such as
      plumage molt.

PMID- 19393654
TI  - Structural evolution of urotensin-I: reflections of life before corticotropin
      releasing factor.
AB  - Peptides have a long evolutionary history that predates the appearance of
      metazoans. The corticotropin releasing factor (CRF) family of peptides is among
      the most ancient peptide lineages. The identification and characterization of
      urotensin-I and related orthologues led the way for the elucidation of the entire
      CRF peptide family. A comparative analysis of the CRF paralogue sequences suggest
      that CRF is the most derived of these peptides and has lost many of its ancestral
      characteristics after it became associated with the hypothalamic-pituitary
      adrenal/interrenal (HPA/I axis). In vertebrates, the urotensin-I group of
      orthologues, which includes sauvagine and urocortin, possess a number of shared
      characteristics that may be indicative of the ancestral peptide. Given the early
      origin of the CRF family peptides, it is likely that other peptide lineages are
      distantly related to the CRF family. In silico or cDNA library screening using
      probes based on urotensin-I/urocortin characteristics have been used to identify
      novel CRF family and related sequences that provide clues the evolutionary origin
      of the CRF family.

PMID- 19393655
TI  - Neuroendocrinology of reproduction in teleost fish.
AB  - This review aims at synthesizing the most relevant information regarding the
      neuroendocrine circuits controlling reproduction, mainly gonadotropin release, in
      teleost fish. In teleosts, the pituitary receives a more or less direct
      innervation by neurons sending projections to the vicinity of the pituitary
      gonadotrophs. Among the neurotransmitters and neuropeptides released by these
      nerve endings are gonadotrophin-releasing hormones (GnRH) and dopamine, acting as
      stimulatory and inhibitory factors (in many but not all fish) on the liberation
      of LH and to a lesser extent that of FSH. The activity of the corresponding
      neurons depends on a complex interplay between external and internal factors that
      will ultimately influence the triggering of puberty and sexual maturation. Among
      these factors are sex steroids and other peripheral hormones and growth factors,
      but little is known regarding their targets. However, very recently a new actor
      has entered the field of reproductive physiology. KiSS1, first known as a tumor
      suppressor called metastin, and its receptor GPR54, are now central to the
      regulation of GnRH, and consequently LH and FSH secretion in mammals. The KiSS
      system is notably viewed as instrumental in integrating both environmental cues
      and metabolic signals and passing this information onto the reproductive axis. In
      fish, there are two KiSS genes, KiSS1 and KiSS2, expressed in neurons of the
      preoptic area and mediobasal hypothalamus. Pionneer studies indicate that KiSS
      and GPR54 expression seem to be activated at puberty. Although precise
      information as to the physiological effects of KiSS1 in fish, notably on GnRH
      neurons and gonadotropin release, is still limited, KiSS neurons may emerge as
      the "gatekeeper" of puberty and reproduction in fish as in mammals.

PMID- 19393656
TI  - Molecular cloning and characterization of olive flounder (Paralichthys olivaceus)
      peroxisome proliferator-activated receptor gamma.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors
      that play key roles in lipid and energy homeostasis. Olive flounder (Paralichthys
      olivaceus) PPARgamma cDNA (olPPARgamma) was isolated by reverse transcription
      polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE).
      The full-length cDNA is 1667-bp long and encodes a polypeptide with 532 amino
      acids containing a C4-type zinc finger and a ligand-binding domain. Quantitative
      RT-PCR revealed that olPPARgamma transcription was detected from 7days post
      hatching, and its expression was increased under a starved condition.
      Overexpression of olPPARgamma stimulated PPAR response element (PPRE) activity,
      and treatment with rosiglitazone, a PPARgamma agonist, augmented olPPARgamma
      stimulated PPRE activity in HINAE olive flounder cells. Cotransfection of
      olPPARgamma and olRXRbeta, in the absence or presence of rosiglitazone and
      ciglitazone, produced a synergistic effect on PPRE transactivation in 3T3L1
      adipocytes. Moreover, olPPARgamma, in the presence or absence of rosiglitazone,
      regulated the expression of lipid synthesis- and adipogenesis-related proteins in
      NIH3T3 and 3T3L1 cells. Taken together, these results suggest that olPPARgamma is
      functionally and evolutionarily conserved in olive flounder and mammals.

PMID- 19393657
TI  - Perspectives on the endocrinology of poultry growth and metabolism.
AB  - Birds have rapid pre- and post-hatching growth rates. The major hormones required
      to support normal growth are growth hormone (GH), triiodothyronine (T(3)) and
      insulin-like growth factor-I (IGF-I). Optimal growth requires a "set-point"
      concentration of both IGF-I and T(3) in the circulation. Pituitary GH plays a
      role in controlling the circulating concentrations of both IGF-I and T(3).
      Nutritional restriction (energy, protein) leads to reductions in circulating
      concentrations of both IGF-I and T(3) with increased GH secretion due removal of
      negative feedback. Similarly, there is un-coupling of the GH-IGF-I axis in
      stunting disease. A critical control point is at the level of the liver and GH
      receptor/signal transduction. The major hormones controlling metabolism include
      glucagon, insulin, adrenal glucocorticoid hormone, corticosterone and potentially
      somatostatin. Chickens and turkeys have higher circulating concentrations of
      glucose than those of livestock mammals. What are not known include the
      following: the biological basis for the high basal glucose concentrations; the
      quantitative fluxes of key metabolites in the fed and fasted state through growth
      and development; the relative contribution of different organs to
      gluconeogenesis; the relative importance of insulin and somatostatin in
      controlling lipolysis and the role of gastro-intestinal hormones in the control
      of metabolism.

PMID- 19393658
TI  - Expression of the gene for ancestral glycoprotein hormone beta subunit in the
      nerve cord of amphioxus.
AB  - Amphioxus belongs to the subphylum cephalochordata, a clade of chordates
      phylogenetically placed at the most basal position. Despite many studies on the
      endocrine system of amphioxus, there were no confident lines of evidence on the
      presence of pituitary hormones, whereas recent amphioxus genome analysis reported
      that amphioxus has no pituitary hormone except for thyrostimulin, which is a
      glycoprotein hormone in the pituitary, brain, and other organs of vertebrates. In
      the present study, we cloned cDNA for one glycoprotein hormone beta subunit (GPB)
      from amphioxus, AmpGPB5, and phylogenetically indicated that AmpGPB5 is the
      ancestral molecule of glycoprotein hormone beta subunits of vertebrates including
      pituitary glycoprotein hormones. Synteny analyses showed conservation of
      chromosomal location of genes near GPB genes from amphioxus through human. The
      AmpGPB5 gene was expressed in a restricted region of the dorsal part of the nerve
      cord, glandular atrial cells of gills, and pre-vitellogenic oocytes in amphioxus.
      However, expression was not detected in the Hatschek's pit which is considered to
      be a primitive pituitary gland. On the basis of present results, we hypothesize
      that a portion of vertebrate pituitary hormones might be derived from an
      ancestral glycoprotein hormone of amphioxus that functions as a neuroendocrine
      hormone.

PMID- 19393659
TI  - Stress hormones mediate environment-genotype interactions during amphibian
      development.
AB  - Environments experienced by organisms during early development shape the
      character and timing of developmental processes, leading to different
      probabilities of survival in the developmental habitat, and often profound
      effects on phenotypic expression later in life. Amphibian larvae have immense
      capacity for plasticity in behavior, morphology, growth and development rate.
      This creates the potential for extreme variation in the timing of, and size at
      metamorphosis, and subsequent phenotype in the juvenile and adult stage. Hormones
      of the neuroendocrine stress axis play pivotal roles in mediating environmental
      effects on animal development. Corticotropin-releasing factor, whose secretion by
      hypothalamic neurons is induced by environmental stress, influences the timing of
      amphibian metamorphosis by controlling the activity of the thyroid and interrenal
      (adrenal; corticosteroids) glands. At target tissues, corticosteroids synergize
      with thyroid hormone to promote metamorphosis. Thus, environmental stress acts
      centrally to increase the activity of the two principle endocrine axes
      controlling metamorphosis, and the effectors of these axes synergize at the level
      of target tissues to promote morphogenesis. While stress hormones can promote
      survival in a deteriorating larval habitat, costs may be incurred such as reduced
      tadpole growth and size at metamorphosis. Furthermore, exposure to elevated
      corticosteroids early in life can cause permanent changes in the expression of
      genes of the neuroendocrine stress axis, leading to altered physiology and
      behavior in the juvenile/adult stage. Persistent effects of stress hormone
      actions early in life may have important fitness consequences.

PMID- 19393660
TI  - Endocrine control of sexual behavior in teleost fish.
AB  - Sexual behavior is one of the most profound events during the life cycle of
      animals that reproduce sexually. After completion of gonadal development that is
      mediated by various hormones, oviparous teleosts perform a suite of behaviors,
      often termed as spawning behavior. This is particularly important for teleosts
      that have their gametes fertilized externally as the behavior patterns ensures
      the close proximity of both sexes for gamete release, fusion and ultimately the
      production of offspring. As in other vertebrates, sexual behavior of fish is also
      under the control of hormones. Testicular androgen is a requirement for male
      sexual behavior to occur in most fish species that have been studied. Unlike
      tetrapods, however, ovarian estrogen does not appear to be essential for the
      occurrence of female sexual behavior for fish that have their gametes fertilized
      externally. Prostaglandins produced in the ovary after ovulation act as a trigger
      in some teleosts to induce female sexual behavior. Potentiating effects of
      gonadotropin-releasing hormone in the brain on sexual behavior are reported in
      some species. Under endocrine regulation, male and female fish exhibit gender
      typical behavior during spawning, but in some fish species there is also some
      plasticity in their sexual behavior. Sex changing fish can perform both male
      typical and female-typical sexual behaviors during their lifetime and this sexual
      plasticity can also be observed in non-sex changing fish when undergoing hormonal
      treatment. Although the neuroanatomical basis is not clear in fish, results of
      field and laboratory observations suggest that some teleosts possess a sexually
      bipotential brain which can regulate two types of behaviors unlike most other
      vertebrates which have a discrete sex differentiation of their brain and can only
      perform gender-typical sexual behavior.

PMID- 19393661
TI  - Competition between intramolecular and intermolecular interactions in an amyloid
      forming protein.
AB  - Despite much progress in understanding the folding and the aggregation processes
      of proteins, the rules defining their interplay have yet to be fully defined.
      This problem is of particular importance since many diseases are initiated by
      protein unfolding and hence the propensity to aggregate competes with
      intramolecular collapse and other folding events. Here, we describe the roles of
      intramolecular and intermolecular interactions in defining the length of the lag
      time and the apparent rate of elongation of the 100-residue protein human beta(2)
      microglobulin at pH 2.5, commencing from an acid-denatured state that lacks
      persistent structure but contains significant non-random hydrophobic
      interactions. Using a combination of site-directed mutagenesis, quantitative
      kinetic analysis and computational methods, we show that only a single region of
      about 10 residues in length, determines the rate of fibril formation, despite the
      fact that other regions exhibit a significant intrinsic propensity for
      aggregation. We rationalise these results by analysing the effect of
      incorporating the conformational properties of acid-unfolded beta(2)
      microglobulin and its variants at pH 2.5 as measured by NMR spectroscopy into the
      Zyggregator aggregation prediction algorithm. These results demonstrate that
      residual structure in the precursor state modulates the intrinsic propensity of
      the polypeptide chain to aggregate and that the algorithm developed here allows
      the key regions for aggregation to be more clearly identified and the rates of
      their self-association to be predicted. Given the common propensity of unfolded
      chains to form non-random intramolecular interactions as monomers and to self
      assemble subsequently into amyloid fibrils, the approach developed should find
      widespread utility for the prediction of regions important in amyloid formation
      and their rates of self-assembly.

PMID- 19393663
TI  - Dynamics, energetics, and selectivity of the low-K+ KcsA channel structure.
AB  - Potassium channels are a diverse family of integral membrane proteins through
      which K(+) can pass selectively. There is ongoing debate about the nature of
      conformational changes associated with the opening/closing and
      conductive/nonconductive states of potassium channels. The channels partly exert
      their function by varying their conductance through a mechanism known as C-type
      inactivation. Shortly after the activation of K(+) channels, their selectivity
      filter stops conducting ions at a rate that depends on various stimuli. The
      molecular mechanism of C-type inactivation has not been fully understood yet.
      However, the X-ray structure of the KcsA channel obtained in the presence of low
      K(+) concentration is thought to be representative of a K(+) channel in the C
      type inactivated state. Here, extensive, fully atomistic molecular dynamics and
      free-energy simulations of the low-K(+) KcsA structure in an explicit lipid
      bilayer are performed to evaluate the stability of this structure and the
      selectivity of its binding sites. We find that the low-K(+) KcsA structure is
      stable on the timescale of the molecular dynamics simulations performed, and that
      ions preferably remain in S1 and S4. In the absence of ions, the selectivity
      filter evolves toward an asymmetric architecture, as already observed in other
      computations of the high-K(+) structure of KcsA and KirBac. The low-K(+) KcsA
      structure is not permeable by Na(+), K(+), or Rb(+), and the selectivity of its
      binding sites is different from that of the high-K(+) structure.

PMID- 19393662
TI  - Active-site gating regulates substrate selectivity in a chymotrypsin-like serine
      protease the structure of haemophilus influenzae immunoglobulin A1 protease.
AB  - We report here the first structure of a member of the immunoglobulin A protease
      (IgAP) family at 1.75-A resolution. This protease is a founding member of the
      type V (autotransporter) secretion system and is considered a virulence
      determinant among the bacteria expressing the enzyme. The structure of the enzyme
      fits that of a classic autotransporter in which several unique domains necessary
      for protein function are appended to a central, 100-A-long beta-helical domain.
      The N-terminal domain of the IgAP is found to possess a chymotrypsin-like fold.
      However, this catalytic domain contains a unique loop D that extends over the
      active site acting as a lid, gating substrate access. The data presented provide
      a structural basis for the known ability of IgAPs to cleave only the
      proline/serine/threonine-rich hinge peptide unique to IgA1 (isotype 1) in the
      context of the intact fold of the immunoglobulin. Based upon the structural data,
      as well as molecular modeling, a model suggesting that the unique extended loop D
      in this IgAP sterically occludes the active-site binding cleft in the absence of
      immunoglobulin binding is presented. Only in the context of binding of the IgA1
      Fc domain in a valley formed between the N-terminal protease domain and another
      domain appended to the beta-helix spine (domain 2) is the lid stabilized in an
      open conformation. The stabilization of this open conformation through Fc
      association subsequently allows access of the hinge peptide to the active site,
      resulting in recognition and cleavage of the substrate.

PMID- 19393664
TI  - Prion protein NMR structure from tammar wallaby (Macropus eugenii) shows that the
      beta2-alpha2 loop is modulated by long-range sequence effects.
AB  - NMR structures are presented for the recombinant construct of residues 121-230
      from the tammar wallaby (Macropus eugenii) prion protein (PrP) twPrP(121-230) and
      for the variant mouse PrPs mPrP[Y225A,Y226A](121-231) and mPrP[V166A](121-231) at
      20 degrees C and pH 4.5. All three proteins exhibit the same global architecture
      as seen in other recombinant PrP(C)s (cellular isoforms of PrP) and shown to
      prevail in natural bovine PrP(C). Special interest was focused on a loop that
      connects the beta2-strand with helix alpha2 in the PrP(C) fold, since there are
      indications from in vivo experiments that this local structural feature affects
      the susceptibility of transgenic mice to transmissible spongiform
      encephalopathies. This beta2-alpha2 loop and helix alpha3 form a solvent
      accessible contiguous epitope, which has been proposed to be the recognition area
      for a hypothetical chaperone, the "protein X". This hypothetical chaperone would
      affect the conversion of PrP(C) into the disease-related scrapie form (PrP(Sc))
      by moderating intermolecular interactions related to the transmission barrier of
      transmissible spongiform encephalopathies between different species. In contrast
      to mPrP(121-231) and most other mammalian PrP(C)s, the beta2-alpha2 loop is well
      defined at 20 degrees C in tammar wallaby PrP and in the two aforementioned
      variants of mPrP, showing that long-range interactions with helix alpha3 can have
      an overriding influence on the structural definition of the beta2-alpha2 loop.
      Further NMR studies with two variant mPrPs, mPrP[Y225A](121-231) and
      mPrP[Y226A](121-231), showed that these interactions are dominantly mediated by
      close contacts between residues 166 and 225. The results of the present study
      then lead to the intriguing indication that well-defined long-range
      intramolecular interactions could act as regulators of the functional specificity
      of PrP(C).

PMID- 19393665
TI  - GroEL can unfold late intermediates populated on the folding pathways of
      monellin.
AB  - The modulation of the folding mechanism of the small protein single-chain
      monellin (MNEI) by the Escherichia coli chaperone GroEL has been studied. In the
      absence of the chaperone, the folding of monellin occurs via three parallel
      routes. When folding is initiated in the presence of a saturating concentration
      of GroEL, only 50-60% of monellin molecules fold completely. The remaining 40-50%
      of the monellin molecules remain bound to the GroEL and are released only upon
      addition of ATP. It is shown that the basic folding mechanism of monellin is not
      altered by the presence of GroEL, but that it occurs via only one of the three
      available routes when folding is initiated in the presence of saturating
      concentrations of GroEL. Two pathways become nonoperational because GroEL binds
      very tightly to early intermediates that populate these pathways in a manner that
      makes the GroEL-bound intermediates incompetent to fold. This accounts for the
      monellin molecules that remain GroEL-bound at the end of the folding reaction.
      The third pathway remains operational because the GroEL-bound early intermediate
      on this pathway is folding-competent, suggesting that this early intermediate
      binds to GroEL in a manner that is different from that of the binding of the
      early intermediates on the other two pathways. It appears, therefore, that the
      same protein can bind GroEL in more than one way. The modulation of the folding
      energy landscape of monellin by GroEL occurs because GroEL binds folding
      intermediates on parallel folding pathways, in different ways, and with different
      affinities. Moreover, when GroEL is added to refolding monellin at different
      times after commencement of refolding, the unfolding of two late kinetic
      intermediates on two of the three folding pathways can be observed. It appears
      that the unfolding of late folding intermediates is enabled by a thermodynamic
      coupling mechanism, wherein GroEL binds more tightly to an early intermediate
      than to a late intermediate on a folding pathway, with preferential binding
      energy being larger than the stability of the late intermediate. Hence, it is
      shown that GroEL can inadvertently and passively cause, through its ability to
      bind different folding intermediates differentially, the unfolding of late
      productive intermediates on folding pathways, and that its unfolding action is
      not restricted solely to misfolded or kinetically trapped intermediates.

PMID- 19393666
TI  - High-resolution structural analysis of a novel octaheme cytochrome c nitrite
      reductase from the haloalkaliphilic bacterium Thioalkalivibrio nitratireducens.
AB  - Bacterial pentaheme cytochrome c nitrite reductases (NrfAs) are key enzymes
      involved in the terminal step of dissimilatory nitrite reduction of the nitrogen
      cycle. Their structure and functions are well studied. Recently, a novel octaheme
      cytochrome c nitrite reductase (TvNiR) has been isolated from the
      haloalkaliphilic bacterium Thioalkalivibrio nitratireducens. Here we present high
      resolution crystal structures of the apoenzyme and its complexes with the
      substrate (nitrite) and the inhibitor (azide). Both in the crystalline state and
      in solution, TvNiR exists as a stable hexamer containing 48 hemes-the largest
      number of hemes accommodated within one protein molecule known to date. The
      subunit of TvNiR consists of two domains. The N-terminal domain has a unique fold
      and contains three hemes. The catalytic C-terminal domain hosts the remaining
      five hemes, their arrangement, including the catalytic heme, being identical to
      that found in NrfAs. The complete set of eight hemes forms a spatial pattern
      characteristic of other multiheme proteins, including structurally characterized
      octaheme cytochromes. The catalytic machinery of TvNiR resembles that of NrfAs.
      It comprises the lysine residue at the proximal position of the catalytic heme,
      the catalytic triad of tyrosine, histidine, and arginine at the distal side,
      channels for the substrate and product transport with a characteristic gradient
      of electrostatic potential, and, finally, two conserved Ca(2+)-binding sites.
      However, TvNiR has a number of special structural features, including a covalent
      bond between the catalytic tyrosine and the adjacent cysteine and the unusual
      topography of the product channels that open into the void interior space of the
      protein hexamer. The role of these characteristic structural features in the
      catalysis by this enzyme is discussed.

PMID- 19393668
TI  - Robust filtering for stochastic genetic regulatory networks with time-varying
      delay.
AB  - This paper addresses the robust filtering problem for a class of linear genetic
      regulatory networks (GRNs) with stochastic disturbances, parameter uncertainties
      and time delays. The parameter uncertainties are assumed to reside in a polytopic
      region, the stochastic disturbance is state-dependent described by a scalar
      Brownian motion, and the time-varying delays enter into both the translation
      process and the feedback regulation process. We aim to estimate the true
      concentrations of mRNA and protein by designing a linear filter such that, for
      all admissible time delays, stochastic disturbances as well as polytopic
      uncertainties, the augmented state estimation dynamics is exponentially mean
      square stable with an expected decay rate. A delay-dependent linear matrix
      inequality (LMI) approach is first developed to derive sufficient conditions that
      guarantee the exponential stability of the augmented dynamics, and then the
      filter gains are parameterized in terms of the solution to a set of LMIs. Note
      that LMIs can be easily solved by using standard software packages. A simulation
      example is exploited in order to illustrate the effectiveness of the proposed
      design procedures.

PMID- 19393667
TI  - Unwinding by local strand separation is critical for the function of DEAD-box
      proteins as RNA chaperones.
AB  - The DEAD-box proteins CYT-19 in Neurospora crassa and Mss116p in Saccharomyces
      cerevisiae are broadly acting RNA chaperones that function in mitochondria to
      stimulate group I and group II intron splicing and to activate mRNA translation.
      Previous studies showed that the S. cerevisiae cytosolic/nuclear DEAD-box protein
      Ded1p could stimulate group II intron splicing in vitro. Here, we show that Ded1p
      complements mitochondrial translation and group I and group II intron splicing
      defects in mss116Delta strains, stimulates the in vitro splicing of group I and
      group II introns, and functions indistinguishably from CYT-19 to resolve
      different nonnative secondary and/or tertiary structures in the Tetrahymena
      thermophila large subunit rRNA-DeltaP5abc group I intron. The Escherichia coli
      DEAD-box protein SrmB also stimulates group I and group II intron splicing in
      vitro, while the E. coli DEAD-box protein DbpA and the vaccinia virus DExH-box
      protein NPH-II gave little, if any, group I or group II intron splicing
      stimulation in vitro or in vivo. The four DEAD-box proteins that stimulate group
      I and group II intron splicing unwind RNA duplexes by local strand separation and
      have little or no specificity, as judged by RNA-binding assays and stimulation of
      their ATPase activity by diverse RNAs. In contrast, DbpA binds group I and group
      II intron RNAs nonspecifically, but its ATPase activity is activated specifically
      by a helical segment of E. coli 23S rRNA, and NPH-II unwinds RNAs by directional
      translocation. The ability of DEAD-box proteins to stimulate group I and group II
      intron splicing correlates primarily with their RNA-unwinding activity, which,
      for the protein preparations used here, was greatest for Mss116p, followed by
      Ded1p, CYT-19, and SrmB. Furthermore, this correlation holds for all group I and
      group II intron RNAs tested, implying a fundamentally similar mechanism for both
      types of introns. Our results support the hypothesis that DEAD-box proteins have
      an inherent ability to function as RNA chaperones by virtue of their distinctive
      RNA-unwinding mechanism, which enables refolding of localized RNA regions or
      structures without globally disrupting RNA structure.

PMID- 19393669
TI  - Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to
      genotoxicity of bystander effects.
AB  - Genomic instability can be observed in bystander cells. However, the underlying
      mechanism(s) is still relatively unclear. In a previous study, we found that
      irradiated cells released mitochondria-dependent intracellular factor(s) which
      could lead to bystander gamma-H2AX induction. In this paper, we used normal
      (rho(+)) and mtDNA-depleted (rho(0)) human-hamster hybrid cells to investigate
      mitochondrial effects on the genotoxicity in bystander effect through medium
      transfer experiments. Through the detection of DNA double-strand breaks with
      gamma-H2AX, we found that the fraction of gamma-H2AX positive cells changed with
      time when irradiation conditioned cell medium (ICCM) were harvested. ICCM
      harvested from irradiated rho(+) cells at 10 min post-irradiation (rho(+) ICCM(10
      min)) caused larger increases of bystander gamma-H2AX induction comparing to
      rho(0) ICCM(10 min), which only caused a slight increase of bystander gamma-H2AX
      induction. The rho(+) ICCM(10 min) could also result in the up-regulation of ROS
      production (increased by 35% at 10 min), while there was no significant increase
      in cells treated with rho(0) ICCM(10 min). We treated cells with dimethyl
      sulfoxide (DMSO), the scavenger of ROS, and quenched gamma-H2AX induction by
      rho(+) ICCM. Furthermore, after the medium had been transferred and the cells
      were continuously cultured for 7 days, we found significantly increased CD59(-)
      gene loci mutation (increased by 45.9%) and delayed cell death in the progeny of
      rho(+) ICCM-treated bystander cells. In conclusion, the work presented here
      suggested that up-regulation of the mitochondria-dependent ROS might be very
      important in mediating genotoxicity of bystander effects.

PMID- 19393670
TI  - lacZ mouse embryonic fibroblasts detect both clastogens and mutagens.
AB  - The clastogenic effects of MMC and BLM and the mutagenic effects of B[a]P, N-ac
      AAF and ENU were studied in mouse embryonic fibroblasts derived from wild-type
      (WT) and Rad54/Rad54B-deficient mice. Clastogens as well as mutagens showed a
      statistically significant induction of mutations in the lacZ reporter gene both
      in a WT and Rad54/Rad54B-deficient genetic background. Rad54/Rad54B MEFs appeared
      equally sensitive to the clastogens compared to WT MEFs, except for MMC. The type
      of mutations induced by the different compounds was investigated further by
      hybridizing the mutant colonies with total mouse DNA. An obvious increased number
      of mouse DNA positive clones was observed after BLM and MMC exposure, indicating
      that after these treatments genome rearrangements/translocations had occurred. In
      this hybridization assay, Rad54/Rad54B MEFs did not show more
      rearrangements/translocations than WT MEFs. As expected, the mutagens used showed
      no increase in chromosomal rearrangements or transloctions in MEFs derived from
      both genotypes. These results show that WT MEFs carrying the lacZ reporter gene
      on a plasmid are capable to detect both clastogenic as well as mutagenic effects
      of compounds in vitro. Deletion of the Rad54 and Rad54B genes did not further
      enhance the sensitivity of MEFs towards clastogens.

PMID- 19393671
TI  - Effects of the histone deacetylase inhibitor sodium butyrate in models of
      depression and anxiety.
AB  - Histone modification, which affects the rate of transcription without altering
      DNA sequence, occurs in response to various psychiatric drugs and in several
      models of psychiatric disease. As increases in histone acetylation have been seen
      after treatment with antidepressants, we investigated whether directly increasing
      histone acetylation using a histone deacetylase inhibitor would have
      antidepressant effects. We administered sodium butyrate (NaB, 100 mg/kg, i.p.) to
      mice acutely (3 injections over 24 h) or chronically (twice daily for 21 days)
      and subjected them to a number of behavioral tests of antidepressant response.
      This dose of NaB had no effect on overall locomotor activity after either acute
      or chronic treatment. Acutely treated mice showed an increase in immobility in
      the forced-swim test (FST) and an increase in latency to consume in the novel
      environment of the novelty-induced hypophagia (NIH) paradigm, an anxiogenic
      effect. The effect of NaB on anxiety did not generalize to another test, the
      elevated zero maze, where it had no effect. Chronic treatment with NaB had no
      effect on latency to consume in the NIH or immobility in the FST. However, this
      dose did alter histone acetylation in the hippocampus. While H4 acetylation
      increased in the hippocampus 30 min following acute NaB, chronic treatment caused
      a decrease in AcH4. There were no changes in AcH3 following either treatment.
      While changes in chromatin structure may be involved in the mechanism of action
      of antidepressant drugs, these data suggest that increasing histone acetylation
      pharmacologically is not sufficient to produce antidepressant effects.

PMID- 19393672
TI  - Keep cool: memory is retained during hibernation in Alpine marmots.
AB  - Hibernators display severe changes in brain structure during deep torpor,
      including alterations in synaptic constitution. To address a possible effect on
      long-term memory, we examined learning behavior and memory of the hibernator
      Marmota marmota. In two operant conditioning tasks, the marmots learned to jump
      on two boxes or to walk through a tube. The animals were trained during their
      active season. Performance improved during the training phase and remained stable
      in a last test, four weeks before entrance into hibernation. When retested after
      six months of hibernation, skills were found to be unimpaired (box: before
      hibernation: 258.2+/-17.7 s, after hibernation: 275.0+/-19.8 s; tube: before
      hibernation: 158.4+/-9.0 s, after hibernation: 137.7+/-6.3 s). Contrary to these
      findings, memory seemed to be less fixed during the active season, since changes
      in test procedure resulted in impaired test performance. Besides the operant
      conditioning, we investigated the animals' habituation to a novel environment by
      repeated open field exposure. In the first run, animals showed exploratory
      behavior and thus a high locomotor activity was observed (63.6+/-10.7 crossed
      squares). Upon a second exposure, all animals immediately moved into one corner
      and locomotion ceased (7.2+/-1.9 crossed squares). This habituation was not
      altered even after hibernation (6.1+/-1.1 crossed squares). We thus conclude that
      long-term memory is unaffected by hibernation in Alpine marmots.

PMID- 19393673
TI  - Repeated exposure to corticosterone increases depression-like behavior in two
      different versions of the forced swim test without altering nonspecific locomotor
      activity or muscle strength.
AB  - We have recently shown that repeated high dose injections of corticosterone
      (CORT) reliably increase depression-like behavior on a modified one-day version
      of the forced swim test. The main purpose of this experiment was to compare the
      effect of these CORT injections on our one-day version of the forced swim test
      and the more traditional two-day version of the test. A second purpose was to
      determine whether altered behavior in the forced swim test could be due to
      nonspecific changes in locomotor activity or muscle strength. Separate groups of
      rats received a high dose CORT injection (40 mg/kg) or a vehicle injection once
      per day for 21 consecutive days. Then, half the rats from each group were exposed
      to the traditional two-day forced swim test and the other half were exposed to
      our one-day forced swim test. After the forced swim testing, all the rats were
      tested in an open field and in a wire suspension grip strength test. The CORT
      injections significantly increased the time spent immobile and decreased the time
      spent swimming in both versions of the forced swim test. However, they had no
      significant effect on activity in the open field or grip strength in the wire
      suspension test. These results show that repeated CORT injections increase
      depression-like behavior regardless of the specific parameters of forced swim
      testing, and that these effects are independent of changes in locomotor activity
      or muscle strength.

PMID- 19393674
TI  - Effects of chronic and repeated corticosterone administration in rearing chickens
      on physiology, the onset of lay and egg production of hens.
AB  - A corticosterone model was used to study the effects of chronic and repeated
      stress during the rearing phase on physiology, the onset of lay and performance
      of laying hens in the subsequent laying period. Two hundred and seventy Hy-line
      brown layer pullets were reared in environmentally controlled battery cages. At
      7, 11, and 15 weeks of age birds were exposed for 1 week to the following
      treatments in drinking water: corticosterone dissolved in ethanol, ethanol, or
      untreated water. One week following each treatment, and at 35 weeks of age
      endocrine, metabolic and haematological tests were conducted. Body weight was
      measured throughout the study, and egg production was recorded daily throughout
      the laying period. Plasma corticosterone levels and heterophil to lymphocyte
      (H/L) ratio were increased after each corticosterone delivery, showing the
      effectiveness of the treatment. When corticosterone delivery was interrupted,
      plasma corticosterone and H/L ratio were significantly reduced. Exposing birds to
      repeated and long-term corticosterone treatment significantly affected BW
      (P<0.01), and relative organ weights (P<0.01). Corticosterone delivery also
      resulted in increased blood levels of glucose (GLU), cholesterol (CHOL), and
      triglyceride (TRG). Administration of corticosterone during the rearing phase
      delayed the onset of lay and decreased egg production at 35 weeks of age. These
      results demonstrate that oral corticosterone treatment affects hen physiology,
      reduces performance, and may model the effects of production stressors.

PMID- 19393675
TI  - Diclofenac enhances proinflammatory cytokine-induced nitric oxide production
      through NF-kappaB signaling in cultured astrocytes.
AB  - Recently, the number of reports of encephalitis/encephalopathy associated with
      influenza virus has increased. In addition, the use of a non-steroidal anti
      inflammatory drug, diclofenac sodium (DCF), is associated with a significant
      increase in the mortality rate of influenza-associated encephalopathy. Activated
      astrocytes are a source of nitric oxide (NO), which is largely produced by
      inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore,
      we investigated whether DCF enhances nitric oxide production in astrocytes
      stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes
      with three cytokines, interleukin-1beta, tumor necrosis factor-alpha and
      interferon-gamma, and then treated the astrocytes with DCF or acetaminophen (N
      acetyl-p-aminophenol: APAP). iNOS and NO production in astrocyte cultures were
      induced by proinflammatory cytokines. The addition of DCF augmented NO
      production, but the addition of APAP did not. NF-kappaB inhibitors SN50 and MG132
      inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without
      DCF. Similarly, NF-kappaB p65 Stealth small interfering RNA suppressed iNOS gene
      expression in cytokine-stimulated astrocytes with or without DCF. LDH activity
      and DAPI staining showed that DCF induces cell damage in cytokine-stimulated
      astrocytes. An iNOS inhibitor, L-NMMA, inhibited the cytokine- and DCF-induced
      cell damage. In conclusion, this study demonstrates that iNOS and NO are induced
      in astrocyte cultures by proinflammatory cytokines. Addition of DCF further
      augments NO production. This effect is mediated via NF-kappaB signaling and leads
      to cell damage. The enhancement of DCF on NO production may explain the
      significant increase in the mortality rate of influenza-associated encephalopathy
      in patients treated with DCF.

PMID- 19393676
TI  - Purification, characterization and biological activities of the L-amino acid
      oxidase from Bungarus fasciatus snake venom.
AB  - L-amino acid oxidases (LAAOs) are widely distributed in snake venoms, which
      contribute to the toxicity of venoms. However, LAAO from Bungarus fasciatus (B.
      fasciatus) snake venom has not been isolated previously. In the present study,
      LAAO from B. fasciatus snake venom was purified by SP-Sepharose HP anion exchange
      chromatography followed by Heparin-Sepharose FF affinity chromatography procedure
      and the purified enzyme was named BF-LAAO. BF-LAAO presented an estimated
      molecular weight of 55kDa in SDS-PAGE and an apparent molecular weight of 70kDa
      in size-exclusion chromatography suggesting that BF-LAAO is a monomeric protein.
      Kinetics studies showed that BF-LAAO was very active against L-Tyr, L-Asp, L-Phe,
      L-Glu, L-Trp, L-His, L-Gln, L-Ile, L-Met, L-Leu and moderately active against L
      Lys, L-Arg, L-Ala and L-Asn. BF-LAAO exhibited a cytotoxic effect on A549 cells
      and caused up to 41.2% apoptosis of A549 cells following 12h incubation period.
      In the mouse peritoneum, BF-LAAO provoked a marked increase in the number of
      neutrophils, lymphocytes and macrophages following injection. It also induced
      rabbit platelet aggregation in a dose-dependent manner. At 3h following
      injection, BF-LAAO elicited severe inflammation in the gastrocnemius muscles of
      mice, but failed to induce significant organ damage. In conclusion, the cytotoxic
      and proinflammatory activities of BF-LAAO could be the main cause of the local
      inflammation, which helps us to understand the pathogenesis of snakebite.

PMID- 19393677
TI  - Pectenotoxins and yessotoxin from Arica Bay, North Chile as determined by tandem
      mass spectrometry.
AB  - Lipophilic phycotoxins were measured by tandem mass spectrometry coupled to
      liquid chromatography (LC-MS/MS) in size-fractionated plankton samples taken at
      five stations in Arica Bay, northern Chile in the southern summer 2007/2008.
      Pectenotoxins-2 (PTX-2), -11 (PTX-11), -2 seco acid (PTX-2sa) and yessotoxin
      (YTX) were identified by comparison of retention times and collision-induced mass
      spectra of certified standards and field sample extracts. This is the first
      report of PTXs and YTX from planktonic samples in Chilean coastal waters.

PMID- 19393678
TI  - First record of human envenomation by Atractaspis congica Peters, 1877 (Squamata:
      Atractaspididae).
AB  - We describe here the first known documented case of human envenomation by the
      burrowing asp Atractaspis congica. The patient received a single fang puncture in
      the index finger and suffered local pain, discolouration, blistering and swelling
      of the finger, hand and forearm. Analgesics were given, but no antivenom.
      Recovery was complete within 48 h, saves some moderate swelling, blistering and
      hypersensitivity.

PMID- 19393679
TI  - Actions of sea anemone type 1 neurotoxins on voltage-gated sodium channel
      isoforms.
AB  - As voltage-gated Na(+) channels are responsible for the conduction of electrical
      impulses in most excitable tissues in the majority of animals (except nematodes),
      they have become important targets for the toxins of venomous animals, from sea
      anemones to molluscs, scorpions, spiders and even fishes. During their evolution,
      different animals have developed a set of cysteine-rich peptides capable of
      binding different extracellular sites of this channel protein. A fundamental
      question concerning the mechanism of action of these toxins is whether they act
      at a common receptor site in Na(+) channels when exerting their different
      pharmacological effects, or at distinct receptor sites in different Na(v)
      channels subtypes whose particular properties lead to these pharmacological
      differences. The alpha-subunits of voltage-gated Na(+) channels (Na(v)1.x) have
      been divided into at least nine subtypes on the basis of amino acid sequences.
      Sea anemones have been extensively studied from the toxinological point of view
      for more than 40 years. There are about 40 sea anemone type 1 peptides known to
      be active on Na(v)1.x channels and all are 46-49 amino acid residues long, with
      three disulfide bonds and their molecular weights range between 3000 and 5000 Da.
      About 12 years ago a general model of Na(v)1.2-toxin interaction, developed for
      the alpha-scorpion toxins, was shown to fit also to action of sea anemone toxin
      such as ATX-II. According to this model these peptides are specifically acting on
      the type 3 site known to be between segments 3 and 4 in domain IV of the Na(+)
      channel protein. This region is indeed responsible for the normal Na(+) currents
      fast inactivation that is potently slowed by these toxins. This fundamental "gain
      of-function" mechanism is responsible for the strong increase in the action
      potential duration. They constitute a class of tools by means of which
      physiologists and pharmacologists can study the structure/function relationships
      of channel proteins. As most of the structural and electrophysiological studies
      were performed on type 1 sea anemone sodium channel toxins, we will present a
      comprehensive and updated review on the current understanding of the
      physiological actions of these Na channel modifiers.

PMID- 19393680
TI  - New conopeptides of the D-superfamily selectively inhibiting neuronal nicotinic
      acetylcholine receptors.
AB  - The venom of cone snails (Conus spp.) is a rich source of peptides exhibiting a
      wide variety of biological activities. Several of these conopeptides are neuronal
      nicotinic acetylcholine receptor (nAChR) antagonists and belong to the A-, M-, S
      , C and the recently described D-superfamily (alphaD-conopeptides). Here we
      describe the discovery and characterization of two alphaD-conopeptides isolated
      from the venom of Conus mustelinus and Conus capitaneus. Their primary structure
      was determined by Edman degradation, MS/MS analysis and by a PCR based approach.
      These peptides show close structural homology to the alphaD-VxXIIA, -B and -C
      conopeptides from the venom of Conus vexillum and are dimers (about 11kDa) of
      similar or identical peptides with 49 amino acid residues and a characteristic
      arrangement of ten conserved cysteine residues. These novel types of conopeptides
      specifically block neuronal nAChRs of the alpha7, alpha3beta2 and alpha4beta2
      subtypes in nanomolar concentrations. Due to their high affinity, these new
      ligands may provide a tool to decipher the localisation and function of the
      various neuronal nAChRs.

PMID- 19393681
TI  - Local envenoming by the Western hognose snake (Heterodon nasicus): a case report
      and review of medically significant Heterodon bites.
AB  - A case of clinically significant local envenoming resulting from a bite inflicted
      by a Western hognose snake, Heterodon nasicus, is described. The patient was
      bitten while offering a juvenile mouse to a captive snake. The snake maintained a
      grip on the patient's arm (left anticubital fossa) for several minutes. The bite
      resulted in marked edema, ecchymoses, lymphadenopathy, cutaneous signs suggestive
      of mild cellulitis and blister formation. There were no systemic effects.
      Recovery was complete after approximately five months. Several documented
      Heterodon sp. bites with significant clinical effects are reviewed. This common
      xenodontine colubrid must be considered capable of inflicting medically
      significant bites. It is currently unclear whether the pathological changes
      associated with these bites are due to specific Duvernoy's secretion components,
      Type I hypersensitivity or a combination of these. The influence of the feeding
      response on the severity of clinical effects is considered as is the discrepancy
      between experimentally verified pharmacological activities of Duvernoy's
      secretions from Heterodon sp. and medical sequelae of documented bites. Although
      hognose snakes may uncommonly produce medically significant bites, they should
      not be considered dangerous or venomous. Captive specimens should be handled
      carefully, particularly when offered food.

PMID- 19393682
TI  - Morphological and ultrastructural effects of microcystin-LR from Microcystis
      aeruginosa extract on a kidney cell line.
AB  - The aim of this study was to examine the toxic effects of a microcystin-LR (MCLR)
      containing cyanobacteria extract on the subcellular organization of a kidney cell
      line (Vero-E6). Cells were exposed to different MCLR concentrations (1.3-150
      microM) for 24, 48 and 72h and two cytotoxicity assays were performed. This
      information was combined with the analysis of lysosomal, mitochondrial and
      cytoskeleton integrity and with an ultrastructural study. Biochemical and
      microscopic data revealed a good agreement and demonstrated that cellular
      response to MCLR is dependent on the dose/exposure time. Cell viability decayed
      markedly after 24h of exposure to toxin concentrations greater than 30 microM.
      Furthermore, it was demonstrated that lysosome destabilization precedes
      mitochondria dysfunction. The ultrastructural analysis showed that mild toxin
      incubation conditions induce endoplasmic reticulum (ER) vacuolization and
      assembly of large autophagic vacuoles, suggesting that autophagy is an early
      cellular response to the toxin. After exposure to higher MCLR doses, the number
      of apoptotic cells increased, as identified by microscopic observations and
      confirmed with TUNEL assay. Additionally, drastic exposure conditions induced the
      increase of necrotic cells. These results suggest that the ER is the primary
      microcystin target in Vero cells and that autophagy, apoptosis and necrosis are
      induced in a dose- and time-dependent manner.

PMID- 19393683
TI  - Steroids and neuroprotection: New advances.
AB  - Gonadal hormones exert neuroprotective actions. In addition, it has become
      evident that the local synthesis of these molecules in the central nervous system
      may prevent or reduce neurodegeneration.The neuroprotective actions of steroids
      involve neurons, glial cells and blood vessels, are exerted via steroid receptor
      signaling initiated at the nuclear or membrane level and steroid receptor
      independent mechanisms. They include the regulation of phosphatases and kinases
      and the regulation of the expression of molecules controlling inflammation and
      apoptosis. In addition, mitochondria have emerged as new central targets for
      neuroprotective actions of steroids. These neuroprotective actions have been
      documented in different experimental models of neurological alterations,
      including motoneuron injury, Parkinson's disease, traumatic brain injury,
      multiple sclerosis, stroke and Alzheimer's disease. In addition, steroids promote
      serotonergic neuronal function and protect against affective disorders. This
      special issue of Frontiers in Neuroendocrinology contains a collection of reviews
      of the most recent ideas and findings on these various aspects of sex steroid
      dependent neuroprotection

PMID- 19393685
TI  - Impact of sex steroids on neuroinflammatory processes and experimental multiple
      sclerosis.
AB  - Synthetic and natural estrogens as well as progestins modulate neuronal
      development and activity. Neurons and glia are endowed with high-affinity steroid
      receptors. Besides regulating brain physiology, both steroids conciliate
      neuroprotection against toxicity and neurodegeneration. The majority of data
      derive from in vitro studies, although more recently, animal models have proven
      the efficaciousness of steroids as neuroprotective factors. Indications for a
      safeguarding role also emerge from first clinical trials. Gender-specific
      prevalence of degenerative disorders might be associated with the loss of
      hormonal activity or steroid malfunctions. Our studies and evidence from the
      literature support the view that steroids attenuate neuroinflammation by reducing
      the pro-inflammatory property of astrocytes. This effect appears variable
      depending on the brain region and toxic condition. Both hormones can individually
      mediate protection, but they are more effective in cooperation. A second research
      line, using an animal model for multiple sclerosis, provides evidence that
      steroids achieve remyelination after demyelination. The underlying cellular
      mechanisms involve interactions with astroglia, insulin-like growth factor-1
      responses, and the recruitment of oligodendrocytes.

PMID- 19393686
TI  - Cannabidiol reverses the reduction in social interaction produced by low dose
      Delta(9)-tetrahydrocannabinol in rats.
AB  - While Delta(9)-tetrahydrocannabinol (THC) is the main psychoactive constituent of
      the cannabis plant, a non-psychoactive constituent is cannabidiol (CBD). CBD has
      been implicated as a potential treatment of a number of disorders including
      schizophrenia and epilepsy and has been included with THC in a 1:1 combination
      for the treatment of conditions such as neuropathic pain. This study investigated
      the effect of THC and CBD, alone or in combination, on some objective behaviours
      of rats in the open field. Pairs of rats were injected with CBD or vehicle
      followed by THC or vehicle and behaviour in the open field was assessed for 10
      min. In vehicle pretreated rats THC (1 mg/kg) significantly reduced social
      interaction between rat pairs. Treatment with CBD had no significant effect
      alone, but pretreatment with CBD (20 mg/kg) reversed the THC-induced decreases in
      social interaction. A higher dose of THC (10 mg/kg) produced no significant
      effect on social interaction. However, the combination of high dose CBD and high
      dose THC significantly reduced social interaction between rat pairs, as well as
      producing a significant decrease in locomotor activity. This data suggests that
      CBD can reverse social withdrawal induced by low dose THC, but the combination of
      high dose THC and CBD impairs social interaction, possibly by decreasing
      locomotor activity.

PMID- 19393684
TI  - Neuroprotective actions of androgens on motoneurons.
AB  - Androgens have a variety of protective and therapeutic effects in both the
      central and peripheral nervous systems. Here we review these effects as they
      related specifically to spinal and cranial motoneurons. Early in development,
      androgens are critical for the formation of important neuromuscular sex
      differences, decreasing the magnitude of normally occurring cell death in select
      motoneuron populations. Throughout the lifespan, androgens also protect against
      motoneuron death caused by axonal injury. Surviving motoneurons also display
      regressive changes to their neurites as a result of both direct axonal injury and
      loss of neighboring motoneurons. Androgen treatment enhances the ability of
      motoneurons to recover from these regressive changes and regenerate both axons
      and dendrites, restoring normal neuromuscular function. Androgens exert these
      protective effects by acting through a variety of molecular pathways. Recent work
      has begun to examine how androgen treatment can interact with other treatment
      strategies in promoting recovery from motoneuron injury.

PMID- 19393687
TI  - Discriminative stimulus effects of ethanol, pregnanolone, and
      dehydroepiandrosterone (DHEA) in rats administered ethanol or saline as
      adolescents.
AB  - Adolescent alcohol use may produce long-term changes in the receptors and
      neurosteroids that putatively mediate alcohol's effects and consequently
      contribute to alcohol abuse and dependence as an adult. To test this possibility,
      ethanol (0.18-1.8 g/kg) and two neurosteroids, pregnanolone (1-10 mg/kg) and
      dehydroepiandrosterone (DHEA, 1-100 mg/kg), were administered alone and in
      combination to adult, male Long-Evans rats discriminating 1 g/kg ethanol (15%
      v/v) under a fixed ratio (FR) 20 schedule of food presentation after adolescent
      treatment with 15 injections of ethanol (n = 9, 2 g/kg, 20% v/v) or saline (n =
      7). When compared as adults, ethanol-treated adolescents (as opposed to saline
      treated adolescents) had higher percentages of ethanol-lever responding at doses
      smaller than the training dose, and higher response rates after both control and
      ethanol injections. Neither pregnanolone nor DHEA substituted for ethanol in
      either adolescent-treated group up to doses that substantially decreased response
      rates. When administered with ethanol, 1 and 3.2 mg/kg of pregnanolone enhanced
      the discriminative stimulus effects of small ethanol doses more in saline-treated
      adolescents than in ethanol-treated adolescents. Unlike pregnanolone, 32 and 100
      mg/kg of DHEA attenuated the discriminative stimulus effects of ethanol modestly
      in both adolescent-treated groups. These results in adult rats suggest that
      adolescent ethanol administration can enhance the discriminative stimulus effects
      of small ethanol doses and affect the capacity of pregnanolone, but not DHEA, to
      interact with ethanol's discriminative stimulus effects.

PMID- 19393688
TI  - Passive immunization with a nicotine-specific monoclonal antibody decreases brain
      nicotine levels but does not precipitate withdrawal in nicotine-dependent rats.
AB  - Vaccination against nicotine is under investigation as a treatment for tobacco
      dependence. Passive immunization with nicotine-specific antibodies represents a
      complementary strategy to vaccination. A potential adverse effect of passive
      immunization in nicotine-dependent individuals is that it may lead to a rapid
      reduction in brain nicotine levels and trigger withdrawal. The goal of this study
      was to determine if passive immunization with the nicotine-specific monoclonal
      antibody Nic311 precipitated withdrawal in nicotine-dependent rats as measured by
      increases in brain reward thresholds and somatic signs. Another cohort of rats
      was used to measure brain nicotine levels after Nic311 administration. Nic311 30,
      80 or 240 mg/kg reduced brain nicotine concentrations by 45, 83 or 92% compared
      to controls. None of these Nic311 doses precipitated withdrawal measured at
      intervals up to 72 h following antibody administration. Administration of the
      nicotinic antagonist mecamylamine precipitated a robust nicotine withdrawal
      syndrome. Therefore, a substantial, but not complete, acute reduction in brain
      nicotine levels following passive immunization was not sufficient to precipitate
      nicotine withdrawal in nicotine-dependent rats. The Nic311 doses used have been
      shown to attenuate the behavioral effects of nicotine, suggesting that the use of
      passive immunization to treat nicotine addiction is not likely to precipitate
      withdrawal.

PMID- 19393689
TI  - High levels of hair manganese in children living in the vicinity of a ferro
      manganese alloy production plant.
AB  - Manganese (Mn) is an essential element, but an effective toxic at high
      concentrations. While there is an extensive literature on occupational exposure,
      few studies have examined adults and children living near important sources of
      airborne Mn. The objective of this study was to analyze hair Mn of children
      living in the vicinity of a ferro-manganese alloy production plant in the Great
      Salvador region, State of Bahia, Brazil and examine factors that influence this
      bioindicator of exposure. We examined 109 children in the age range of 1-10
      years, living near the plant. Four separate housing areas were identified a
      priori on the bases of proximity to the emission sources and downwind location. A
      non-exposed group (n=43) of similar socio-economic status was also evaluated. Mn
      hair (MnH) concentration was measured by graphite atomic absorption spectrometry
      (GFAAS). Possible confounding hematological parameters were also assessed. Mean
      MnH concentration was 15.20 microg/g (1.10-95.50 microg/g) for the exposed
      children and 1.37 microg/g (0.39-5.58 microg/g) for the non-exposed. For the
      former, MnH concentrations were 7.95+/-1.40 microg/g (farthest from the plant),
      11.81+/-1.11 microg/g (mid-region), 34.43+/-8.66 microg/g (closest to the plant)
      and 34.22+/-9.15 microg/g (directly downwind). Multiple regression analysis on
      log transformed MnH concentrations for the exposed children derived a model that
      explained 36.8% of the variability. In order of importance, area of children's
      residence, gender (girls>boys) and time of mother's residence in the area at the
      birth of the child, were significantly associated with MnH. Post hoc analyses
      indicated two groupings for exposure areas, with those living closest to and
      downwind of the plant displaying higher MnH concentrations compared to the
      others. The contribution of the time the mother lived in the community prior to
      the child's birth to the children's current MnH suggests that in utero exposure
      may play a role. A study of neurobehavioral performance with respect to Mn
      exposure in these children is currently underway.

PMID- 19393690
TI  - Glycine transporter inhibitors as a novel drug discovery strategy for neuropathic
      pain.
AB  - Injury to peripheral or spinal nerves following either trauma or disease has
      several consequences including the development of neuropathic pain. This syndrome
      is often refractory against conventional analgesics; and thus, novel medicaments
      are desired for its treatment. Recent studies have emphasized that dysfunction of
      inhibitory neuronal regulation of pain signal transduction may be relevant to the
      development of neuropathic pain. Glycinergic neurons are localized in specific
      brain regions and the spinal cord, where they play an important role in the
      prevention of pathological pain symptoms. Thus, an enhancement of glycinergic
      control in the spinal cord is a promising strategy for pain relief from
      neuropathic pain. Glycine transporter (GlyT) 1 and GlyT2, which are located in
      glial cells and neurons, respectively play important roles by clearing
      synaptically released glycine or supplying glycine to glycinergic neurons to
      regulate glycinergic neurotransmission. Thus, an inhibition of GlyTs could be
      used to modify pain signal transmission in the spinal cord. Recently developed
      specific inhibitors of GlyTs have made this possibility a reality. Both GlyT1 and
      GlyT2 inhibitors produced potential anti-nociceptive effect in various
      neuropathic pain models, chronic and acute inflammatory models in animals. Their
      anti-allodynia effects are mediated by the inhibition of GlyTs following
      activation of spinal glycine receptor alpha3. These results established GlyTs as
      target molecules for medicaments for neuropathic pain. Moreover, the phase
      dependent anti-allodynia effects of GlyT inhibitors have provided important
      information on effective therapeutic strategies and also understanding the
      underlying molecular mechanisms of the development of neuropathic pain.

PMID- 19393693
TI  - Recruitment of human aquaporin 3 to internal membranes in the Plasmodium
      falciparum infected erythrocyte.
AB  - The molecular mechanisms underlying the formation of the parasitophorous vacuolar
      membrane in Plasmodium falciparum infected erythrocytes are incompletely
      understood, and the protein composition of this membrane is still enigmatic.
      Although the differentiated mammalian erythrocyte lacks the machinery required
      for endocytosis, some reports have described a localisation of host cell membrane
      proteins at the parasitophorous vacuolar membrane. Aquaporin 3 is an abundant
      plasma membrane protein of various cells, including mammalian erythrocytes where
      it is found in distinct oligomeric states. Here we show that human aquaporin 3 is
      internalized into infected erythrocytes, presumably during or soon after
      invasion. It is integrated into the PVM where it is organized in novel oligomeric
      states which are not found in non-infected cells.

PMID- 19393692
TI  - An efficient and reproducible method for quantifying macrophages in different
      experimental models of central nervous system pathology.
AB  - Historically, microglia/macrophages are quantified in the pathological central
      nervous system (CNS) by counting cell profiles then expressing the data as
      cells/mm(2). However, because it is difficult to visualize individual cells in
      dense clusters and in most cases it is unimportant to know the absolute number of
      macrophages within lesioned tissue, alternative methods may be more efficient for
      quantifying the magnitude of the macrophage response in the context of different
      experimental variables (e.g., therapeutic intervention or time post
      injury/infection). The present study provides the first in-depth comparison of
      different techniques commonly used to quantify microglial/macrophage reactions in
      the pathological spinal cord. Individuals from the same and different
      laboratories applied techniques of digital image analysis (DIA), standard cell
      profile counting and a computer-assisted cell counting method with unbiased
      sampling to quantify macrophages in focal inflammatory lesions, disseminated
      lesions caused by autoimmune inflammation or at sites of spinal trauma. Our goal
      was to find a simple, rapid and sensitive method with minimal variability between
      trials and users. DIA was consistently the least variable and most time-efficient
      method for assessing the magnitude of macrophage responses across lesions and
      between users. When used to evaluate the efficacy of an anti-inflammatory
      treatment, DIA was 5-35 x faster than cell counting and was sensitive enough to
      detect group differences while eliminating inter-user variability. Since lesions
      are clearly defined and single profiles of microglia/macrophages are difficult to
      discern in most pathological specimens of brain or spinal cord, DIA offers
      significant advantages over other techniques for quantifying activated
      macrophages.

PMID- 19393691
TI  - Pharmacological profiles of alpha 2 adrenergic receptor agonists identified using
      genetically altered mice and isobolographic analysis.
AB  - Endogenous, descending noradrenergic fibers impose analgesic control over spinal
      afferent circuitry mediating the rostrad transmission of pain signals. These
      fibers target alpha 2 adrenergic receptors (alpha(2)ARs) on both primary afferent
      terminals and secondary neurons, and their activation mediates substantial
      inhibitory control over this transmission, rivaling that of opioid receptors
      which share a similar pattern of distribution. The terminals of primary afferent
      nociceptive neurons and secondary spinal dorsal horn neurons express alpha(2A)AR
      and alpha(2C)AR subtypes, respectively. Spinal delivery of these agents serves to
      reduce their side effects, which are mediated largely at supraspinal sites, by
      concentrating the drugs at the spinal level. Targeting these spinal alpha(2)ARs
      with one of five selective therapeutic agonists, clonidine, dexmedetomidine,
      brimonidine, ST91 and moxonidine, produces significant antinociception that can
      work in concert with opioid agonists to yield synergistic antinociception.
      Application of several genetically altered mouse lines had facilitated
      identification of the primary receptor subtypes that likely mediate the
      antinociceptive effects of these agents. This review provides first an anatomical
      description of the localization of the three subtypes in the central nervous
      system, second a detailed account of the pharmacological history of each of the
      six primary agonists, and finally a comprehensive report of the specific
      interactions of other GPCR agonists with each of the six principal alpha(2)AR
      agonists featured.

PMID- 19393694
TI  - Ceramide synthase 1 is regulated by proteasomal mediated turnover.
AB  - Ceramide is an important bioactive lipid, intimately involved in many cellular
      functions, including the regulation of cell death, and in cancer and
      chemotherapy. Ceramide is synthesized de novo from sphinganine and acyl CoA via a
      family of 6 ceramide synthase enzymes, each having a unique preference for
      different fatty acyl CoA substrates and a unique tissue distribution. However,
      little is known regarding the regulation of these important enzymes. In this
      study we focus on ceramide synthase 1 (CerS1) which is the most structurally and
      functionally distinct of the enzymes, and describe a regulatory mechanism that
      specifically controls the level of CerS1 via ubiquitination and proteasome
      dependent protein turnover. We show that both endogenous and ectopically
      expressed CerS1 have rapid basal turnover and that diverse stresses including
      chemotherapeutic drugs, UV light and DTT can induce CerS1 turnover. The turnover
      requires CerS1 activity and is regulated by the opposing actions of p38 MAP
      kinase and protein kinase C (PKC). p38 MAP kinase is a positive regulator of
      turnover, while PKC is a negative regulator of turnover. CerS1 is phosphorylated
      in vivo and activation of PKC increases the phosphorylation of the protein. This
      study reveals a novel and highly specific mechanism by which CerS1 protein levels
      are regulated and which directly impacts ceramide homeostasis.

PMID- 19393695
TI  - An ultrasensitive rapid immunocytotoxicity assay for detecting Clostridium
      difficile toxins.
AB  - We describe a novel ultrasensitive cell-based immunocytotoxicity assay for
      detecting Clostridium difficile toxin A and B. The assay is simple to perform
      with a turnaround time of approximately 3 h . It is particularly sensitive in
      detecting TcdA at a level less then 1 pg/ml. Using this assay, we were able to
      detect the presence of C. difficile toxins in the fecal and serum specimens of
      experimentally infected piglets.

PMID- 19393696
TI  - Thiamylal antagonizes the inhibitory effects of dorsal column stimulation on
      dorsal horn activities in humans.
AB  - In humans, peripheral somatosensory information converges upon dorsal horn
      neurons in the spinal cord, which can be recorded from the dorsal epidural space
      as spinal cord potentials (SCPs) following segmental dorsal root stimulation (SS)
      employing epidural catheter electrodes. Antidromic action potentials and
      descending inhibition from the dorsolateral funiculus may contribute to SCPs
      following dorsal column stimulation (DCS). Effects of thiamylal (2.5-7.5 mg/kg,
      i.v.) on SCPs evoked by independent DCS or SS were compared with those evoked by
      simultaneous DCS and SS (DCS/SS). DCS- and SS-evoked SCPs recorded from the
      lumbar enlargement consisted of a sharp negative (N) followed by a slow positive
      (P) potential. Thiamylal induced dose-dependent increases in amplitude and
      duration of both N and P potentials evoked by DCS and SS, whether the responses
      were summed or evoked simultaneously. In awake subjects, N and P potentials
      produced by simultaneous DCS/SS were significantly smaller than the sum of
      independent responses. Thiamylal anesthesia antagonized this inhibition;
      responses to simultaneous DCS/SS were larger than the sum of independent
      responses. These results suggest that in wakefulness DCS inhibits dorsal horn
      neuron activity in the lumbar spinal cord, while thiamylal antagonizes DCS
      induced inhibition in dose-dependent fashion.

PMID- 19393697
TI  - Molecular-assisted refolding: study of two different ionic forms of recombinant
      human fibroblast growth factors.
AB  - Despite several early reports on the refolding-enhancement effect of a stimuli
      responsive polymer, Eudragit, the exact mechanism by which Eudragit interacts
      with protein molecules to improve refolding remains not well-understood. This
      study provides clear elucidation of the mode of involvement of Eudragit in
      facilitating the refolding of two ionic forms of human fibroblast growth factor:
      (i) human basic fibroblast growth factor (hbFGF) and (ii) human acidic fibroblast
      growth factor (haFGF). Eudragit enhanced the refolding yield of hbFGF to 74% at
      0.5 mg ml(-1) refolding protein concentration, but had little effect on its
      acidic counterpart. Spectroscopic and chromatographic analyses provide clear
      biomolecular evidence that the oppositely charged polymer and hbFGF protein
      interact during refolding by forming an ionic complex. This ionic conjugation
      shields exposed hydrophobic residues of the hbFGF refolding intermediates, thus
      minimizing hydrophobic-prone aggregation of the molecules. The refolded hbFGF
      protein can be readily dissociated from the polymer by ion-exchange
      chromatography. Circular dichroism spectroscopy confirmed that the interaction
      between Eudragit and hbFGF during refolding did not compromise the final refolded
      protein structure. This study conclusively shows that Eudragit exhibits charge
      selectivity in its role as a refolding enhancer, which will have a significant
      impact on its future use as a refolding additive.

PMID- 19393698
TI  - Hydrogen peroxide sensor based on horseradish peroxidase immobilized
      nanostructured cerium oxide film.
AB  - Nanostructured cerium oxide (NanoCeO(2)) film deposited onto indium-tin-oxide
      (ITO) glass substrate by solution casting has been used for immobilization of
      horseradish peroxidase (HRP) via physiosorption technique. X-ray diffraction
      (XRD), scanning electron microscopy (SEM), UV-vis and electrochemical techniques
      have been utilized for characterization of NanoCeO(2)/ITO electrode and
      HRP/NanoCeO(2)/ITO bioelectrode. The HRP/NanoCeO(2)/ITO electrode exhibits value
      of the apparent Michaelis-Menten constant (K(m)) as 2.21 microM, linear
      regression coefficient as 0.998 and linearity for hydrogen peroxide as 1.0-170
      microM obtained using electrochemical response measurements. Besides this,
      HRP/NanoCeO(2)/ITO bioelectrode can be used about 20 times and is stable for 5
      weeks at 4 degrees C. The results of photo-response studies carried out on
      HRP/NanoCeO(2)/ITO bioelectrode indicate reasonable agreement with those obtained
      using amperometric technique.

PMID- 19393699
TI  - Single mutation at the amino acid position 627 of PB2 that leads to increased
      virulence of an H5N1 avian influenza virus during adaptation in mice can be
      compensated by multiple mutations at other sites of PB2.
AB  - To understand the adaptation of H5N1 influenza viruses to mammals, a non
      pathogenic influenza H5N1 virus (HN021) in mice was passaged for 15 times in
      mammalian host. Animal experimental results indicated that the mouse-adapted (MA)
      variants became highly pathogenic in mice after the passages. Sequence analysis
      showed that there was one amino acid substitution in PB2 protein of MA mutants
      after first passage (MA1), three amino acid substitutions in PB2 protein of MA5
      and one amino acid in M1 protein, seven amino acids in HA protein and seven amino
      acids in PB2 protein of MA15, respectively. Animal experiments and growth assays
      with reassortant viruses produced by reverse genetics showed that mutations in
      PB2 alone contributed to the increase in virulence of HN021 in mice. Polymerase
      activity assays showed that the mutations in PB2 enhanced ribonucleoprotein
      complex polymerase activity in mammalian cells. Interestingly, one reverse
      mutation (K627E) took place at the amino acid position 627 of PB2 during passages
      of MA5 to MA15, indicating that a lysine at position 627 of PB2 is not absolutely
      needed for virulence and adaptation in mice by H5N1 virus. Taken together, the
      results suggest that mutations at multiple sites of PB2 contributed to the
      virulence and adaptation in mice, and the E627K mutation of PB2 is not an
      indispensable determinant in PB2 for mammalian adaptation by H5N1 avian influenza
      virus.

PMID- 19393700
TI  - Full genomic sequence analysis of swine genotype 3 hepatitis E virus isolated
      from Shanghai.
AB  - The full genomic nucleotide sequence of a previously identified genotype 3
      hepatitis E virus (HEV), strain SAAS-JDY5, was obtained using RT-PCR and rapid
      amplification of cDNA ends (RACE). The genome consisted of 7225 nucleotides,
      excluding a poly-A tail at the 3' terminus, and contained three open reading
      frames (ORFs), ORF-1, ORF-2 and ORF-3, encoding 1702, 660 and 113 amino acids,
      respectively. Phylogenetic analysis confirmed that SAAS-JDY5 belonged to genotype
      3 HEV and was most closely related to the Japanese isolate wbJYG1 (AB222184).
      SAAS-JDY5 shared approximately 87% nucleotide similarity to human and swine
      strains from the United States, compared with 74-75% similarity to Asian
      (genotype 4) and Mexican strains (genotype 2). Alignment of the SAAS-JDY5 genomic
      sequence with reference sequences of the same genotype revealed one nucleotide
      substitution and one deletion at positions 5145 and 7189 (3' UTR), respectively.
      Moreover, SAAS-JDY5 contained two additional nucleotides (AC) at the very end of
      the 3'-terminus preceding the poly-A tail of the genome. Comparison of the
      putative amino acid sequence encoded by the SAAS-JDY5 genome with sequences of
      other genotype 3 isolates revealed 15 unique amino acid substitutions and one
      deletion in ORF-1, and three substitutions in ORF-2.

PMID- 19393701
TI  - ac109 is required for the nucleocapsid assembly of Autographa californica
      multiple nucleopolyhedrovirus.
AB  - ORF109 (Ac109) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV)
      is a highly conserved gene in all sequenced baculovirus genomes, but its function
      is not known. This paper describes generation of an ac109 knockout virus (Ac
      ac109-KO-GP) and analyses of the influence of ac109 deletion on the virus
      replication in Sf-9 cells so as to investigate the role of ac109 in the viral
      life cycle. Results revealed that budded virus (BV) yields and occlusion body
      synthesis were completely blocked in cells infected with the mutant virus.
      Electron microscopy demonstrated that ac109 deletion blocked nucleocapsid
      formation, though infection was initiated and electron-dense bodies associated
      with the virogenic stroma appeared. The mutant phenotype was rescued by an ac109
      rescue virus. On the other hand, real-time PCR analysis indicated that ac109 is
      not required for viral DNA replication. Thus, these results suggested that ac109
      plays an important role in AcMNPV nucleocapsid formation.

PMID- 19393702
TI  - Transepithelial transport of PEGylated anionic poly(amidoamine) dendrimers:
      implications for oral drug delivery.
AB  - The purpose of this work was to assess the impact of PEGylation on
      transepithelial transport of anionic poly(amidoamine) dendrimers. Cytotoxicity,
      uptake and transport across Caco-2 cells of PEGylated G3.5 and G4.5 PAMAM
      dendrimers were studied. Methoxy polyethylene glycol (750 Da) was conjugated to
      carboxylic acid-terminated PAMAM dendrimers at feed ratios of 1, 2 and 4 PEG per
      dendrimer. Compared to the control, PEGylation of anionic dendrimers did not
      significantly alter cytotoxicity up to a concentration of 0.1 mM. PEGylation of
      G3.5 dendrimers significantly decreased cellular uptake and transepithelial
      transport while PEGylation of G4.5 dendrimers led to a significant increase in
      uptake, but also a significant decrease in transport. Dendrimer PEGylation
      reduced the opening of tight junctions as evidenced by confocal microscopy
      techniques. Modulation of the tight junctional complex correlated well with
      changes in PEGylated dendrimer transport and suggests that anionic dendrimers are
      transported primarily through the paracellular route. PEGylated dendrimers show
      promise in oral delivery applications where increased functionality for drug
      conjugation and release is desired.

PMID- 19393704
TI  - Tissue-specific and transcription factor-mediated nuclear entry of DNA.
AB  - Low levels of gene transfer and a lack of tissue-specific targeting of vectors
      have limited the therapeutic potential of non-viral gene therapy. This is due to
      the numerous cellular barriers that hinder nuclear delivery of vectors and the
      paucity of methods that restrict expression to specific cells types. In non
      dividing cells, the nuclear envelope is an especially problematic hurdle to gene
      transfer. Given that the majority of target tissues are non-dividing in vivo, the
      nuclear membrane is a major obstacle to therapeutic gene transfer. In this
      review, the various barriers to gene transfer are discussed. In particular, the
      role of the nuclear pore complex (NPC) in regulating passage of plasmid vectors
      during interphase is reviewed. Several methods of modifying plasmid (pDNA)
      vectors to enhance nuclear import through the NPC are also discussed, including
      the use of tissue-specific transcription factors to mediate nuclear entry of pDNA
      in a cell-specific manner.

PMID- 19393703
TI  - Transcriptional targeting of tumor endothelial cells for gene therapy.
AB  - It is well known that angiogenesis plays a critical role in the pathobiology of
      tumors. Recent clinical trials have shown that inhibition of angiogenesis can be
      an effective therapeutic strategy for patients with cancer. However, one of the
      outstanding issues in anti-angiogenic treatment for cancer is the development of
      toxicities related to off-target effects of drugs. Transcriptional targeting of
      tumor endothelial cells involves the use of specific promoters for selective
      expression of therapeutic genes in the endothelial cells lining the blood vessels
      of tumors. Recently, several genes that are expressed specifically in tumor
      associated endothelial cells have been identified and characterized. These
      discoveries have enhanced the prospectus of transcriptionally targeting tumor
      endothelial cells for cancer gene therapy. In this manuscript, we review the
      promoters, vectors, and therapeutic genes that have been used for transcriptional
      targeting of tumor endothelial cells, and discuss the prospects of such
      approaches for cancer gene therapy.

PMID- 19393705
TI  - Transcriptionally regulated, prostate-targeted gene therapy for prostate cancer.
AB  - Prostate cancer is the most frequently diagnosed cancer and the second leading
      cause of cancer deaths in American males today. Novel and effective treatment
      such as gene therapy is greatly desired. The early viral based gene therapy uses
      tissue-nonspecific promoters, which causes unintended toxicity to other normal
      tissues. In this chapter, we will review the transcriptionally regulated gene
      therapy strategy for prostate cancer treatment. We will describe the development
      of transcriptionally regulated prostate cancer gene therapy in the following
      areas: (1) Comparison of different routes for best viral delivery to the
      prostate; (2) Study of transcriptionally regulated, prostate-targeted viral
      vectors: specificity and activity of the transgene under several different
      prostate-specific promoters were compared in vitro and in vivo; (3) Selection of
      therapeutic transgenes and strategies for prostate cancer gene therapy (4)
      Oncolytic virotherapy for prostate cancer. In addition, the current challenges
      and future directions in this field are also discussed.

PMID- 19393706
TI  - Short interfering RNA-mediated gene silencing; towards successful application in
      human patients.

PMID- 19393707
TI  - Diphtheria: a zoonotic disease in France?
AB  - Thanks to vaccination, diphtheria has almost disappeared in France. The case
      definition, used for mandatory notification, was expanded in 2003 to include
      toxin-producing strains of Corynebacterium ulcerans. We describe the epidemiology
      of diphtheria in France from 1990 to 2008. No cases occurred between 1990 and
      2001. Since 2002, 19 cases have been reported: 4 cases due to Corynebacterium
      diphtheriae related to exposure in endemic countries, and 15 cases due to other
      corynebacteria, including 4 cases of pseudomembranous pharyngitis, mainly related
      to contact with domestic animals. High vaccination coverage in the population and
      sensitive surveillance need to be maintained. Moreover, control measures need to
      be adapted to the non-C. diphtheriae toxigenic species.

PMID- 19393708
TI  - Overview of the disease burden of invasive pneumococcal disease in Asia.
AB  - This paper represents a collaborative effort by the Asian Strategic Alliance for
      Pneumococcal Disease Prevention (ASAP) Working Group to collate data on the
      disease burden due to invasive pneumococcal disease (IPD) in participating Asian
      countries and territories; namely, Hong Kong, India, Indonesia, Korea, Macau,
      Malaysia, Pakistan, the Philippines, Singapore, Sri Lanka, Taiwan and Thailand. A
      review of both published and unpublished data revealed that the incidence of IPD
      in some countries is well documented by way of large, long-duration studies,
      while in other countries, much of the available data have been extrapolated from
      international studies or have come from small population studies of limited
      geographical coverage. This paper confirms that data regarding the incidence of
      IPD in Asia are grossly lacking and reinforces the need for urgent and more
      substantial studies.

PMID- 19393709
TI  - Bordetella pertussis monophosphoryl lipid A as adjuvant for inactivated split
      virion influenza vaccine in mice.
AB  - The world production capacity of influenza vaccines is a concern in face of the
      potential influenza pandemic. The use of adjuvants could increase several fold
      the current installed production capacity. Bordetella pertussis monophosphyl
      lipid A (MPLA) was produced by acid hydrolysis of LPS, obtained as a by-product
      of its removal from cellular pertussis vaccine, generating a product with 4 side
      chains. We have investigated different formulations including MPLA alone or
      combined with Al(OH)(3) as adjuvants for an inactivated split virion influenza
      vaccine. Our results demonstrate that MPLA at concentrations as low as 0.01
      microg per dose of vaccine is effective, even with a 4-fold reduction of the
      regular vaccine dose, as measured by the induction of protective hemagglutination
      inhibition (HAI) titers. Al(OH)(3) can be combined with 0.01-10 microg MPLA,
      inducing even higher immune responses. Al(OH)(3) caused a drift of the immune
      response induced by the vaccine towards a Th2 profile, as evaluated by an
      increase in the IgG1:IgG2a ratio, while MPLA showed a more balanced response.
      Moreover, the use of MPLA and Al(OH)(3) combination led to the induction of the
      highest IgG levels together with the secretion of both IFN-gamma and IL-4.
      Although cell-mediated immune responses have not been usually taken into account
      for influenza vaccine formulations, they may be relevant for the induction of
      cross-protection as well as immunological memory for both inter-pandemic and
      pandemic influenza vaccines. Our results indicate that a more favorable profile
      of both humoral and cell-mediated immune responses may be obtained using the
      MPLA/Al(OH)(3) formulation.

PMID- 19393710
TI  - Q-fever vaccination--unfinished business in Australia.

PMID- 19393711
TI  - National paediatric immunization program of high risk groups: no effect on the
      incidence of invasive pneumococcal diseases.
AB  - This study monitors the epidemiology of invasive pneumococcal diseases (IPD) in
      hospitalized children up to 60 months of age before (February 2001-October 2004)
      and after (November 2004-January 2007) the introduction of a national risk group
      immunization program with "Prevenar" in Austria. The IPD incidence rates, per
      100,000, for IPD were 7.6 before and 6.4 after the risk group immunization
      program, while there was a significant reduction (p<0.05) for meningitis, 3.1
      before and 1.6 after. Overall, the most commonly observed serotypes were 14
      (34.2%), 6B (11.7%), and 23F (6.7%). 71.7% of the identified strains were vaccine
      types; 12.5% were vaccine-related serotypes. No clinically relevant changes in
      the incidence rate of IPDs or shift/replacement of serotypes was documented.
      Antimicrobial resistance predominated against erythromycin (32.5%) and
      clarithromycin (26.7%). Our data show that this risk group vaccination program
      had no impact on the incidence of IPD in young children.

PMID- 19393712
TI  - The neurobiology of Meditation and its clinical effectiveness in psychiatric
      disorders.
AB  - This paper reviews the evidence for changes of Meditation on body and brain
      physiology and for clinical effectiveness in disorders of psychiatry. The aim of
      Meditation is to reduce or eliminate irrelevant thought processes through
      training of internalised attention, thought to lead to physical and mental
      relaxation, stress reduction, psycho-emotional stability and enhanced
      concentration. Physiological evidence shows a reduction with Meditation of stress
      related autonomic and endocrine measures, while neuroimaging studies demonstrate
      the functional up-regulation of brain regions of affect regulation and attention
      control. Clinical studies show some evidence for the effectiveness of Meditation
      in disorders of affect, anxiety and attention. The combined evidence from
      neurobiological and clinical studies seems promising. However, a more thorough
      understanding of the neurobiological mechanisms of action and clinical
      effectiveness of the different Meditative practices is needed before Meditative
      practices can be leveraged in the prevention and intervention of mental illness.

PMID- 19393714
TI  - A Condition-Enumeration Tree method for mining biclusters from DNA microarray
      data sets.
AB  - Biclustering, which performs simultaneous clustering of rows (e.g., genes) and
      columns (e.g., conditions), has proved of great value for finding interesting
      patterns from microarray data. To find biclusters, a model called pCluster was
      proposed. A pCluster consists of a set of genes and a set of conditions, where
      the expression levels of these genes have a similar variation under these
      conditions. Based on this model, most of the previous methods need to compute
      MDSs (maximum dimension sets) for every two genes in the microarray data. Since
      the number of genes is far larger than the number of conditions, this step is
      inefficient. Another method called MicroCluster was proposed. This method does
      not compute MDSs for every two genes, and transforms the problem into a graph
      problem. However, it needs to solve the Maximal Clique problem, which is NP
      Complete. To avoid the above disadvantages, in this paper, we propose a new
      method, CE-Tree (Condition-Enumeration Tree), for finding pClusters. Instead of
      generating MDSs for every two genes, we generate only MDSs for every two
      conditions. Then, based only on these MDSs, we expand the CE-Tree in a special
      local breadth-first within global depth-first manner to efficiently find all
      pClusters. We also utilize the idea of the traditional hash join approach to
      efficiently support the CE-Tree. From the simulation results, we show that the CE
      Tree method could find pClusters more efficiently than those previous methods.

PMID- 19393713
TI  - Effects of sex, phase of the menstrual cycle and gonadal hormones on pain in
      healthy humans.
AB  - Sex differences in pain have been noted; women typically report more pain than
      men. Gonadal hormones may influence pain reports, and, moreover, such hormones
      may help to explain sex differences and menstrual cycle differences in pain. This
      study measured venipuncture and intravenous catherization pain during the
      follicular and luteal phases of the menstrual cycle in regularly menstruating
      women. Pain was also assessed in a group of men. Pain ratings were higher in
      women than men. In women, pain ratings did not differ between the follicular and
      luteal phases. Estradiol and progesterone increased from follicular to luteal
      phases. Within-phase analyses revealed that pain ratings were positively
      correlated with estradiol and progesterone during the luteal phase. Moreover,
      increases in estradiol and progesterone across the menstrual cycle were
      positively correlated with increases in pain. These findings suggest that
      variations in gonadal hormones during the menstrual cycle influence the
      experience of pain in healthy women.

PMID- 19393715
TI  - microRNA involvement in developmental and functional aspects of the nervous
      system and in neurological diseases.
AB  - microRNAs, small non-coding RNAs that regulate gene expression at the post
      transcriptional level, are emerging as important regulatory molecules involved in
      the fine-tuning of gene expression during neuronal development and function.
      microRNAs have roles during neuronal stem cell commitment and early
      differentiation as well as in later stages of neuronal development, such as
      dendritogenesis and synaptic plasticity. A link between microRNAs and
      neurological diseases, such as neurodegeneration or synaptic dysfunction, is
      becoming increasingly clear. This review summarizes the current knowledge of the
      function of microRNAs in the developing and adult nervous system and their
      potential contribution to the etiology of neurological diseases.

PMID- 19393716
TI  - Corticotropin-releasing factor is a downstream mediator of the beta-melanocyte
      stimulating hormone-induced anorexigenic pathway in chicks.
AB  - Proopiomelanocortin (POMC, a precursor of anorexigenic neuropeptides) neurons in
      hypothalamus suppresses food intake in both mammals and chickens. In mammals,
      several lines of evidence suggest that POMC-derived anorexigenic peptides
      upregulate mRNA levels of anorexigenic peptides such as corticotropin-releasing
      factor (CRF) and thyrotropin-releasing factor and downregulate mRNA levels of
      orexigenic peptides such as orexin and melanin-concentrating hormone. However,
      the POMC-induced anorexigenic pathway in chickens has not been well
      characterized. In the present study, we investigated how POMC neurons regulate
      mechanisms of food intake using an anorexigenic peptide, beta-melanocyte
      stimulating hormone (beta-MSH), derived from the post-transcriptional cleavage of
      POMC. Central administration of beta-MSH in chicks significantly suppressed food
      intake, and importantly, this suppression was accompanied by a significant
      upregulation of CRF mRNA levels. Furthermore, the CRF type 2 receptor antagonist
      alpha-helical CRF significantly reversed the anorexigenic action of beta-MSH.
      These findings indicate that CRF and its receptor, CRF type 2 receptor, act as
      the major mediators in beta-MSH-induced anorexigenic action in chicks. beta-MSH
      significantly increased orexin mRNA levels and did not alter mRNA levels of
      thyrotropin-releasing factor and melanin-concentrating hormone in chicks,
      suggesting that the beta-MSH-induced anorexigenic pathway in chicks is different
      from that in mammals. Increases in orexin mRNA levels were accompanied by
      significant decreases in plasma glucose concentration, suggesting that orexin
      mRNA might be stimulated by beta-MSH-induced hypoglycemia. Thus, this study
      demonstrates the direct evidence that CRF is a critical downstream target in the
      beta-MSH-induced anorexigenic pathway in chicks.

PMID- 19393717
TI  - Impaired attention network in temporal lobe epilepsy: a resting FMRI study.
AB  - Attention deficit is a common symptom in the patient with mesial temporal lobe
      epilepsy (mTLE). Although presumption has been proposed by the previous study
      that mTLE may have impaired attention networks, no fMRI study has addressed the
      alteration of the dorsal attention network in mTLE. Twenty-four patients with
      bilateral mTLE and the same number of gender- and age-matched healthy controls
      participated in the current fMRI study. The resting-state network corresponding
      to the dorsal attention network (DAN) was extracted by using independent
      component analysis (ICA) from each participant. Functional connectivity in the
      DAN was then compared between the patients and controls. In addition, the scores
      of Trail Making Test (TMT) in the patients were correlated to the z-score of the
      voxels showing significant difference between the two groups. Compared with the
      controls, the patients with mTLE presented decreased functional connectivity in
      almost all the regions within the DAN. Moreover, there were negative correlations
      between the TMT scores and the z-scores in the voxels showing decreased or
      increased functional connectivity in mTLE. Our results suggested that the
      alteration of DAN might underpin the impairment of top-down attention function in
      mTLE. Our fMRI study may contribute to the understanding of neuro
      pathophysiological mechanism of attention impairments in patients with mTLE.

PMID- 19393718
TI  - Combination of modified SHIRPA and pharmacological approach uncovers neuronal
      alteration in senescence-accelerated mouse prone 6 (SAMP6) strain.
AB  - The senescence-accelerated mouse (SAM) is a murine model of aging that was
      developed from the AKR/J strain. We examined whether there are behavioral
      differences among SAM prone 6 (SAMP6; an established model of senile
      osteoporosis), SAM resistant 1 (SAMR1), and AKR/J, using a modified
      SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA)
      procedure and pharmacological tests. The modified SHIRPA, which is suitable for
      rapid and comprehensive phenotyping of transgenic and gene-targeted mice,
      revealed increased rearing, spontaneous activity, locomotor activity, tail
      elevation, head bobbing, and tail rattling behaviors of SAMP6 compared with SAMR1
      and AKR/J. These phenotypes are consistent with alteration of the dopamine system
      in SAMP6. Adopting a pharmacological approach to examine dopamine signaling, we
      evaluated the locomotor activity of the mice after intraperitoneal administration
      of apomorphine, a subtype non-selective dopamine receptor agonist. Apomorphine at
      1mg/kg significantly increased the locomotor activity of SAMP6, but not SAMR1 or
      AKR/J. At 3mg/kg, apomorphine significantly increased the locomotor activities of
      all three strains, but the increase in SAMP6 was still significantly greater than
      that in SAMR1 or AKR/J. These results indicate increased sensitivity of the
      dopamine receptor signaling pathway in SAMP6. Thus, alteration of dopamine
      receptor signal transduction appears to be one of the underlying mechanisms of
      the increased locomotor activity of SAMP6. The combination of modified SHIRPA and
      examination of drug threshold dose differences between strains appears to be an
      effective approach to extend the applicability of existing mouse models.

PMID- 19393719
TI  - In situ hybridization is a necessary experimental complement to microRNA (miRNA)
      expression profiling in the human brain.
AB  - MicroRNAs (miRNAs) play fundamental roles in human brain neurochemistry. However,
      much remains to be learned in this fast-paced field. To understand how miRNAs
      contribute to normal biologic functions and disease states, it is critical to
      understand the miRNAs that are expressed in particular cell types under a range
      of conditions. Many tools have been developed to help describe the repertoire of
      miRNAs present at the tissue level in a given sample. However, tissue level miRNA
      profiling is inadequate to pinpoint the cellular and sub-cellular distribution of
      individual miRNAs. Such knowledge is especially important in the nervous system
      with its many cell types, microscopic heterogeneity with regard to functionally
      distinct cell groups, and extreme geometrical complexity in cellular shapes. We
      have found that in situ hybridization shows important cerebral cortical lamina
      specific patterns of miRNA expression that would be lost on most tissue level
      expression studies, and these lamina-specific patterns can be directly relevant
      to human brain disease. Thus, in situ hybridization is an important experimental
      complement to tissue level miRNA expression profiling. Technical and theoretical
      aspects of this important technique are described, especially those pertinent to
      studying the human brain.

PMID- 19393720
TI  - beta-Glucan attenuates TLR2- and TLR4-mediated cytokine production by microglia.
AB  - Microglia, the resident immune cells of the brain, are activated in response to
      any kind of CNS injury, and their activation is critical for maintaining
      homeostasis within the CNS. However, during inflammatory conditions, sustained
      microglial activation results in damage to surrounding neuronal cells. beta
      Glucans are widely recognized immunomodulators, but the molecular mechanisms
      underlying their immunomodulatory actions have not been fully explored. We
      previously reported that beta-glucans activate microglia through Dectin-1 without
      inducing significant amount of cytokines and chemokines. Here, we show that
      particulate beta-glucans attenuate cytokine production in response to TLR
      stimulation; this inhibitory activity of beta-glucan is mediated by Dectin-1 and
      does not require particle internalization. At the molecular level, beta-glucan
      suppressed TLR-mediated NF-kappaB activation, which may be responsible for the
      diminished capacity of microglia to produce cytokines in response to TLR
      stimulation. Overall, these results suggest that beta-glucans may be used to
      prevent or treat excessive microglial activation during chronic inflammatory
      conditions.

PMID- 19393721
TI  - Elevated hepatic iron: a confounding factor in chronic hepatitis C.
AB  - Historically, iron overload in the liver has been associated with the genetic
      disorders hereditary hemochromatosis and thalassemia and with unusual dietary
      habits. More recently, elevated hepatic iron levels also have been observed in
      chronic hepatitis C virus (HCV) infection. Iron overload in the liver causes many
      changes including induction of oxidative stress, damage to lysosomes and
      mitochondria, altered oxidant defense systems and stimulation of hepatocyte
      proliferation. Chronic HCV infection causes numerous pathogenic changes in the
      liver including induction of endoplasmic reticulum stress, the unfolded protein
      response, oxidative stress, mitochondrial dysfunction and altered growth control.
      Understanding the molecular and cellular changes that could occur in a liver
      which has elevated hepatic iron levels and in which HCV replication and gene
      expression are ongoing has clinical relevance and represents an area of research
      in need of further investigation.

PMID- 19393723
TI  - Hyper-excitability in low threshold mechanical A fibers is potentially involved
      in scorpion BmK sting pain.
AB  - In the present study, using the single fiber recording technique, we found that
      BmK I, the main toxic component in scorpion Buthus martensi Karsch (BmK) venom,
      induced dramatic increase in excitability of rapidly adapting (RA) and type I
      slowly adapting (SAI) low threshold mechanical A fibers of rat. Five micrograms
      BmK I (691 nmol, in 10 microl saline) administrated to the receptive fields
      induced spontaneous activity in 80% of RA and SAI fibers, increased the response
      to 10 g-10 s stimulation at about 20 times and altered the firing pattern to
      burst mode with maximal NS (number of spikes in burst) averaging from all fibers
      studied as many as 59. The increase in the excitability of RA and SAI fibers did
      not recover completely in 2h. Our finding suggests that the gigantic abnormal
      activity in low threshold mechanical A fibers is involved in BmK scorpion sting
      pain, and the experimental model of BmK scorpion sting pain can be used to study
      A-fiber related central pathway which is important for relief of refractory
      neuropathic pain likewise.

PMID- 19393722
TI  - Genetic contributions to avoidance-based decisions: striatal D2 receptor
      polymorphisms.
AB  - Individuals differ in their tendencies to seek positive decision outcomes or to
      avoid negative ones. At the neurobiological level, our model suggests that phasic
      changes in dopamine support learning to reinforce good decisions via striatal D1
      receptors, and to avoid maladaptive choices via striatal D2 receptors.
      Accordingly, in a previous study individual differences in positive and negative
      learning were strongly modulated by two genetic polymorphisms factors related to
      striatal D1 and D2 function, respectively. Nevertheless, whereas the role for
      dopamine in positive learning is relatively well accepted, that in learning to
      avoid negative outcomes is more controversial. Here we further explore D2
      receptor-related genetic contributions to probabilistic avoidance in humans, in
      light of recent data showing that particular DRD2 polymorphisms are associated
      with functional modulation of receptor expression [Zhang Y, Bertolino A, Fazio L,
      Blasi G, Rampino A, Romano R, Lee M-LT, Xiao T, Papp A, Wang D, Sadee W (2007)
      Polymorphisms in human dopamine d2 receptor gene affect gene expression,
      splicing, and neuronal activity during working memory. Proc Natl Acad Sci U S A
      104(51):20552-20557]. We find that a promoter polymorphism rs12364283 associated
      with transcription and D2 receptor density was strongly and selectively
      predictive of avoidance-based decisions. Two further polymorphisms (rs2283265 and
      rs1076560) associated with relatively reduced presynaptic relative to
      postsynaptic D2 receptor expression were predictive of relative impairments in
      negative compared to positive decisions. These previously undocumented effects of
      DRD2 polymorphisms were largely independent of those we reported previously for
      the C957T polymorphism (rs6277) associated with striatal D2 density. In contrast,
      effects of the commonly studied Taq1A polymorphism on reinforcement-based
      decisions were due to indirect association with C957T. Taken together these
      findings suggest multiple D2-dependent genetic mechanisms contributing to
      avoidance. We discuss these effects in the context of neurocomputational models
      of reinforcement leaning in the basal ganglia.

PMID- 19393724
TI  - Acute administration of ketamine reverses the inhibition of mitochondrial
      respiratory chain induced by chronic mild stress.
AB  - Modulation and dysfunction of the glutamatergic system seems to be involved in
      depression. Recently a renewed interest in the glutamatergic system as a
      treatment option for major depression emerged by the finding that the glutamate N
      methyl-D-aspartate (NMDA) antagonist ketamine leads to a rapid improvement of
      depressive symptoms. Several works support the hypothesis that metabolism
      impairment is involved in the pathophysiology of depression. We have also
      recently reported that mitochondrial respiratory chain complexes I, III and IV
      were inhibited in cerebral cortex and cerebellum of rats after 40 days of chronic
      mild stress (CMS), which is used as an animal model of depression. Thus, we
      investigated whether the inhibition of these enzymes may be reversed by acute
      administration of ketamine (15 mg/kg). We verified that CMS decreased the intake
      of sweet food and ketamine was not able to reverse such effect. Adrenal gland
      weight was increased in stressed rats and ketamine reversed this alteration.
      Control group gained weight after 40 days but stressed group did not gain weight
      after the same period. Stressed animals gained weight after acute administration
      of ketamine, when compared to the body weight assessed at the beginning of the
      experiment. Finally, we verified that complexes I, III and IV were inhibited
      after CMS in cerebral cortex and cerebellum and acute administration of ketamine
      reversed this inhibition. Based on the present findings, we hypothesized that CMS
      induces inhibition of mitochondrial respiratory chain (complexes I, III and IV)
      and that acute administration of ketamine reverses such effect.

PMID- 19393725
TI  - Diazepam and pentobarbital protect against scorpion venom toxin-induced epilepsy.
AB  - We have characterized earlier the long-term behavioural, electroencephalographic
      and histopatologic features after a single TsTx microinjection, consisting of a
      neuropeptide isolated from the Tityus serrulatus scorpion venom, into the
      hippocampus of rats. TsTx was able to induce status epilepticus (SE) and
      developed later epilepsy. The present study was designed to investigate the
      outcomes of diazepam plus pentobarbital administered at 30 min, 1, 2 or 6h after
      the beginning of TsTx-induced SE, on the development of spontaneous recurrent
      motor seizures (SRMSs), mossy fibre sprouting and hippocampal neurodegeneration
      in rats. The administration of diazepam (DZ)+pentobarbital (PB) 30 min after the
      beginning of the TsTx-induced SE was able to markedly reduce the frequency of the
      SRMSs and prevent the development of mossy fibres sprouting and hippocampal
      lesion. In the other groups the augment of the extent of hipocampal
      neurodegeneration, the frequency of SRMSs and degree of aberrant mossy fibre
      sprouting was directly proportional to the time that the animals were subjected
      to TsTx-induced SE. In conclusion, our results point out that the early blockade
      of the TsTx-induced SE with diazepam plus pentobarbital, was effective treatment
      against later epilepsy development. The effectiveness of this treatment depends
      on the time that the animals were subjected to the SE. Furthermore, the TsTx
      model could be a useful tool to study antiepileptogenic drugs in chronic
      epileptic animals, neuronal degeneration, as well as for the mechanisms
      underlying epilepsy.

PMID- 19393726
TI  - Spatial and temporal expression patterns of diverse Pin-II proteinase inhibitor
      genes in Capsicum annuum Linn.
AB  - Pin-II type proteinase inhibitor (PI) genes were cloned from fruit and stem
      tissues of Capsicum annuum L. var Phule Jyoti using primers designed from
      reported CanPI gene sequence (AF039398). In total, 21 novel CanPIs, members of
      the Pin-II PI family, were identified in the study, with three isoforms of 1
      inhibitory repeat domain (IRD), eight isoforms of 2-IRD, three isoforms of 3-IRD,
      five isoforms of 4-IRD and two partial CanPI sequences. Most of the sequences
      showed variation (2 to 20%) in the deduced AA sequences which were pronounced
      close to the reactive site loop. Expression patterns of CanPIs in the fruit and
      stem tissues of mature C. annuum plants were shown to vary qualitatively and
      quantitatively using semi-quantitative RT-PCR expression analysis. In the fruit
      tissue, CanPIs with different IRDs (from 1 to 4) were expressed simultaneously.
      In stem tissue, 1- and 2-IRD CanPIs were strongly expressed along moderate
      expression of 3- and 4-IRD genes. Analysis of CanPI protein activity showed a
      range of active forms across the tissues. CanPI expression was differentially up
      regulated upon wounding and insect attack. Although infestation by aphids (Myzus
      persicae) and lepidopteran pests (Spodoptera litura) specifically induced 4-IRD
      CanPIs, virus-infected leaves did not affect CanPI expression. Analysis of CanPI
      protein activity indicated that the up-regulation in CanPI expression was not
      always correlated with increase in PI activity. Our results demonstrated that
      CanPI expression is regulated spatially, temporally as well as qualitatively and
      quantitatively.

PMID- 19393727
TI  - Genotoxic activation of the environmental pollutant 3,6-dinitrobenzo[e]pyrene in
      Salmonella typhimurium umu strains expressing human cytochrome P450 and N
      acetyltransferase.
AB  - 3,6-Dinitrobenzo[e]pyrene (DNBeP) is a potent mutagen identified in surface soil
      in two metropolitan areas of Japan. We investigated whether DNBeP can cause
      genotoxicity through any metabolic activation pathway in bacteria using the
      parental strain Salmonella enterica serovar Typhimurium (S. typhimurium)
      TA1535/pSK1002, nitroreductase (NR)-deficient strain NM1000, the O
      acetyltransferase (O-AT)-deficient strain NM2000, bacterial O-AT-overexpressing
      strain NM2009, and bacterial NR- and O-AT-overexpressing strain NM3009
      established in our laboratory. To further clarify the role of human cytochrome
      P450 (P450 or CYP) and N-acetyltransferase (NAT) enzymes in the bioactivation of
      DNBeP to genotoxic metabolites, we determined the genotoxicity of DNBeP using a
      variety of umu tester strains expressing human P450 and NAT enzymes. The dose
      dependent induction of umuC by DNBeP was observed at concentrations between 0.01
      and 1nM in the O-AT-expression strain, but not in the O-AT-deficient strain. In
      the CYP3A4-, CYP1A2-, CYP1A1-, and CYP1B1-expressing strains, DNBeP was found to
      be activated to reactive metabolites that cause the induction of umuC gene
      expression compared with the parent strain. The induction of DNBeP in the NAT2
      expressing strain had a 10-fold lower concentration than that in the NAT1
      expressing strain. Collectively, these results suggest that nitroreduction by
      human CYP1A2, CYP3A4, and CYP1A1 and O-acetylation by human NAT2 contributed to
      the genotoxic activation of DNBeP to its metabolites.

PMID- 19393728
TI  - Delayed liver injury and impaired hepatocyte proliferation after carbon
      tetrachloride exposure in BPOZ2-deficient mice.
AB  - BPOZ2 is a tumor suppressive mediator in PTEN signaling pathway and plays an
      important role in cell proliferation. In this study, we investigated the
      physiology functions of BPOZ2 in CCl(4)-induced liver injury and hepatocyte
      proliferation afterwards. After acute CCl(4) administration, BPOZ2 null mice
      exhibited delayed liver injury and impaired hepatocyte proliferation, which was
      accompanied by altered kinetics of CYP2E1 protein expression, compromised cyclin
      D1 expression and shortened duration of ERK activation. These results for the
      first time define that BPOZ2 is an important regulator involved in the injury and
      repair process induced by acute CC1(4) administration in mouse liver.

PMID- 19393729
TI  - Cardiospermum halicacabum ethanol extract inhibits LPS induced COX-2, TNF-alpha
      and iNOS expression, which is mediated by NF-kappaB regulation, in RAW264.7
      cells.
AB  - AIM OF THIS STUDY: Cardiospermum halicacabum L. is well known for its anti
      inflammatory, analgesic and antipyretic activities. It has been used in Ayurveda
      and folk medicine for the treatment of rheumatism, fever and earache. But its
      mechanism of anti-inflammatory and analgesic action is still unclear, hence in
      this context, the objective of our study is to reveal the mechanism of anti
      inflammatory and analgesic activity of Cardiospermum halicacabum L. which would
      form an additional proof to the traditional knowledge of Cardiospermum
      halicacabum L. MATERIALS AND METHODS: In this study the ethanolic extract of the
      whole plant was used to evaluate the anti-inflammatory action in mouse macrophage
      cell line RAW264.7 cells. The expression levels of cyclooxygenase (COX)-1, COX-2,
      tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS)
      and COX-2 protein expression by semi-quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) and western blot and nuclear factor kappa-B
      (NF-kappaB) binding activity by electrophoretic mobility shift assay (EMSA).
      RESULTS: We found that the ethanol extract dose dependently inhibit mRNA
      expression of COX-2, TNF-alpha, iNOS and COX-2 protein expression. But the
      extract did not affect the expression of COX-1 mRNA expression. Furthermore,
      Cardiospermum halicacabum L. ethanol extract inhibited the TNF-alpha induced DNA
      binding activity of NF-kappaB, which was associated with decreased p65 protein
      level in the nucleus in Jurkat cells. CONCLUSION: These results enabled to
      understand the mechanisms behind the anti-inflammatory and analgesic activity of
      Cardiospermum halicacabum L.

PMID- 19393730
TI  - Study on biomass circulation and gasification performance in a clapboard-type
      internal circulating fluidized bed gasifier.
AB  - We investigated the solid particle flow characteristics and biomass gasification
      in a clapboard-type internal circulating fluidized bed reactor. The effect of
      fluidization velocity on particle circulation rate and pressure distribution in
      the bed showed that fluidization velocities in the high and low velocity zones
      were the main operational parameters controlling particle circulation. The
      maximum internal circulation rates in the low velocity zone came almost within
      the range of velocities in the high velocity zone, when u(H)/u(mf)=2.2-2.4 for
      rice husk and u(H)/u(mf)=3.5-4.5 for quartz sand. In the gasification experiment,
      the air equivalence ratio (ER) was the main controlling parameter. Rice husk
      gasification gas had a maximum heating value of around 5000 kJ/m(3) when ER=0.22
      0.26, and sawdust gasification gas reached around 6000-6500 kJ/m(3) when ER=0.175
      0.24. The gasification efficiency of rice husk reached a maximum of 77% at
      ER=0.28, while the gasification efficiency of sawdust reached a maximum of 81% at
      ER=0.25.

PMID- 19393731
TI  - Kinetics of biomass catalytic pyrolysis.
AB  - The Coats-Redfern method was used to analyze the kinetic characteristics of
      biomass catalytic pyrolysis, indicating that it can be described by multi-step
      reactions, rather than as a simple first-order reaction. Friedman model-free
      calculations were used to describe the starting reaction types and the
      corresponding initial kinetic parameters. Finally, nonlinear regression of
      biomass catalytic pyrolysis showed that the reaction mechanism of the whole
      process could be kinetically characterized by three successive reactions: a one
      dimensional diffusion reaction, followed by an apparent first-order reaction, and
      then by a two-dimensional diffusion reaction. The kinetic parameters and
      equations were also calculated.

PMID- 19393732
TI  - Process simulation of single-step dimethyl ether production via biomass
      gasification.
AB  - In this study, we simulated the single-step process of dimethyl ether (DME)
      synthesis via biomass gasification using ASPEN Plus. The whole process comprised
      four parts: gasification, water gas shift reaction, gas purification, and single
      step DME synthesis. We analyzed the influence of the oxygen/biomass and
      steam/biomass ratios on biomass gasification and synthesis performance. The
      syngas H(2)/CO ratio after water gas shift process was modulated to 1, and the
      syngas was then purified to remove H(2)S and CO(2), using the Rectisol process.
      Syngas still contained trace amounts of H(2)S and about 3% CO(2) after
      purification, which satisfied the synthesis demands. However, the high level of
      cold energy consumption was a problem during the purification process. The DME
      yield in this study was 0.37, assuming that the DME selectivity was 0.91 and that
      CO was totally converted. We performed environmental and economic analyses, and
      propose the development of a poly-generation process based on economic
      considerations.

PMID- 19393733
TI  - Water-based woody biorefinery.
AB  - The conversion of biomass into chemicals and energy is essential in order to
      sustain our present way of life. Fossil fuels are currently the predominant
      energy source, but fossil deposits are limited and not renewable. Biomass is a
      reliable potential source of materials, chemicals and energy that can be
      replenished to keep pace with our needs. A biorefinery is a concept for the
      collection of processes used to convert biomass into materials, chemicals and
      energy. The biorefinery is a "catch and release" method for using carbon that is
      beneficial to both the environment and the economy. In this study, we discuss
      three elements of a wood-based biorefinery, as proposed by the SUNY College of
      Environmental Science and Forestry (ESF): hot-water extraction, hydrolysis, and
      membrane separation/concentration. Hemicelluloses are the most easily separable
      main component of woody biomass and thus form the bulk of the extracts obtained
      by hot-water extraction of woody biomass. Hot-water extraction is an important
      step in the processes of woody biomass and product generation, replacing
      alternative costly pre-treatment methods. The hydrolysis of hemicelluloses
      produces 5-carbon sugars (mainly xylose), 6-carbon sugars (mainly glucose and
      mannose), and acetic acid. The use of nano-filtration membranes is an efficient
      technology that can be employed to fractionate hot-water extracts and wood
      hydrolysate. The residual solid mass after hot-water extraction has a higher
      energy content and contains fewer easily degradable components. This allows for
      more efficient subsequent processing to convert cellulose and lignin into
      conventional products.

PMID- 19393734
TI  - Copper tolerance of the biomass crops Elephant grass (Pennisetum purpureum
      Schumach), Vetiver grass (Vetiveria zizanioides) and the upland reed (Phragmites
      australis) in soil culture.
AB  - Pot trials were conducted to study the influence of copper (Cu) on the growth and
      biomass of Elephant grass (EG, Pennisetum purpureum Schumach), Vetiver grass (VG,
      Vetiveria zizanioides) and the upland reed (UR, Phragmites australis). Cu
      toxicity in EG, VG and UR was positively correlated with the total and
      bioavailable Cu concentrations in the soil. Based on the EC50, dry weights, Cu
      contents, chlorophyll contents and photosynthesis rates, the Cu tolerance of the
      three species followed the trend EGNVGNUR. There were no significant differences
      in the unit calorific values among the different plants, though the total
      calorific values of EG were higher than those of VG and UR due to its higher
      biomass. The addition of KH2PO4 to the soil decreased the bioavailability of Cu
      and the Cu uptake by plants. EG could therefore be a good candidate for growth on
      Cu-contaminated soils, especially those improved by phosphate.

PMID- 19393735
TI  - Biomass-oxygen gasification in a high-temperature entrained-flow gasifier.
AB  - The technology associated with indirect biomass liquefaction is currently
      arousing increased attention, as it could ensure a supply of transportation fuels
      and reduce the use of petroleum. The characteristics of biomass-oxygen
      gasification in a bench-scale laminar entrained-flow gasifier were studied in the
      paper. Experiments were carried out to investigate the influence of some key
      factors, including reaction temperature, residence time and oxygen/biomass ratio,
      on the gasification. The results indicated that higher temperature favored H2 and
      CO production. Cold gas efficiency was improved by N10% when the temperature was
      increased from 1000 to 1400 degrees C. The carbon conversion increased and the
      syngas quality was improved with increasing residence time. A shorter residence
      resulted in incomplete gasification. An optimal residence time of 1.6 s was
      identified in this study. The introduction of oxygen to the gasifier strengthened
      the gasification and improved the carbon conversion, but lowered the lower
      heating value and the H2/CO ratio of the syngas. The optimal oxygen/biomass ratio
      in this study was 0.4. The results of this study will help to improve our
      understanding of syngas production by biomass high-temperature gasification.

PMID- 19393736
TI  - Effects of metal catalysts on CO2 gasification reactivity of biomass char.
AB  - The effects of five metal catalysts (K, Na, Ca, Mg, and Fe) on CO(2) gasification
      reactivity of fir char were studied using thermal gravimetric analysis. The
      degree of carbonization, crystal structure and morphology of char samples was
      characterized by X-ray diffractometry (XRD) and scanning electron microscopy
      (SEM). The CO(2) gasification reactivity of fir char was improved through the
      addition of metal catalysts, in the order K>Na>Ca>Fe>Mg. XRD analysis indicated
      that Na and Ca improved the formation of crystal structure, and that Mg enhanced
      the degree of carbon structure ordering. SEM analysis showed that spotted
      activation centers were distributed on the surface of char samples impregnated
      with catalysts. Moreover, a loose flake structure was observed on the surface of
      both K-char and Na-char. Finally, the kinetic parameters of CO(2) gasification of
      char samples were calculated mathematically.

PMID- 19393737
TI  - Comparison of the pyrolysis behavior of lignins from different tree species.
AB  - Despite the increasing importance of biomass pyrolysis, little is known about the
      pyrolysis behavior of lignin--one of the main components of biomass--due to its
      structural complexity and the difficulty in its isolation. In the present study,
      we extracted lignins from Manchurian ash (Fraxinus mandschurica) and Mongolian
      Scots pine (Pinus sylvestris var. mongolica) using the Bjorkman procedure, which
      has little effect on the structure of lignin. Fourier transform infrared (FTIR)
      spectrometry was used to characterize the microstructure of the Bjorkman lignins,
      i.e., milled wood lignins (MWLs), from the different tree species. The pyrolysis
      characteristics of MWLs were investigated using a thermogravimetric analyzer, and
      the release of the main volatile and gaseous products of pyrolysis were detected
      by FTIR spectroscopy. During the pyrolysis process, MWLs underwent thermo
      degradation over a wide temperature range. Manchurian ash MWL showed a much
      higher thermal degradation rate than Mongolian Scots pine MWL in the temperature
      range from 290-430 degrees C. High residue yields were achieved at 37 wt.% for
      Mongolian Scots pine MWL and 26 wt.% for Manchurian ash MWL. In order to further
      investigate the mechanisms of lignin pyrolysis, we also analyzed the FTIR
      profiles for the main pyrolysis products (CO(2), CO, methane, methanol, phenols
      and formaldehyde) and investigated the variation in pyrolysis products between
      the different MWLs.

PMID- 19393738
TI  - Sodium butyrate inhibits Staphylococcus aureus internalization in bovine mammary
      epithelial cells and induces the expression of antimicrobial peptide genes.
AB  - A distinctive feature of bovine milk fat is the presence of butyrate, molecule
      with recognized antimicrobial and antiinflammatory properties. Bovine mastitis is
      a pathology characterized by inflammatory and infectious processes; however, the
      role of sodium butyrate on Staphylococcus aureus infection in mammary epithelium
      has not been studied. In this work we assess the role of sodium butyrate on the
      invasion of bovine mammary epithelial cells (bMEC) by S. aureus responsible of
      mastitis and on the expression of antimicrobial peptide genes. Our data show that
      sodium butyrate (0.25-0.5mM) reduces approximately 50% the internalization of S.
      aureus (ATCC 27543) into bMEC. By RT-PCR analysis, we showed that sodium butyrate
      is able to up-regulate the expression of tracheal antimicrobial peptide (TAP),
      beta-defensin and inducible nitric oxide synthase (iNOS) mRNAs, as well as nitric
      oxide production. Also, sodium butyrate and infection increased acetylation of
      histone H3 in bMEC. These results indicate that sodium butyrate could be
      effective to modulate innate immune gene expression in mammary gland that leads
      to a better defense against bacterial infection. To our knowledge, this is the
      first report that shows a role of sodium butyrate during the internalization of
      S. aureus into bMEC.

PMID- 19393739
TI  - Occurrence, divergence and evolution of intrinsic terminators across eubacteria.
AB  - In Escherichia coli, the canonical intrinsic terminator of transcription includes
      a palindrome followed by a U-trail on the transcript. The apparent
      underrepresentation of such terminators in eubacterial genomes led us to develop
      a rapid and accurate algorithm, GeSTer, to predict putative intrinsic
      terminators. Now, we have analyzed 378 genome sequences with an improved version
      of GeSTer. Our results indicate that the canonical E. coli type terminators are
      not overwhelmingly abundant in eubacteria. The atypical structures, having stem
      loop structures but lacking 'U' trail, occur downstream of genes in all the
      analyzed genomes but different phyla show conserved preference for different
      types of terminators. This propensity correlates with genomic GC content and
      presence of the factor, Rho. 60-70% of identified terminators in all the genomes
      show "optimized" stem-length and DeltaG. These results provide evidence that
      eubacteria extensively rely on the mechanism of intrinsic termination, with a
      considerable divergence in their structure, positioning and prevalence. The
      software and detailed results for individual genomes are freely available on
      request.

PMID- 19393740
TI  - A combination of a SEM technique and X-ray microanalysis for studying the spore
      germination process of Clostridium tyrobutyricum.
AB  - Clostridium tyrobutyricum is an anaerobic bacterium responsible for late blowing
      defects during cheese ripening and it is of scientific interest for biological
      hydrogen production. A scanning electron microscopy (SEM) coating technique and X
      ray microanalysis were developed to analyze the architecture and chemical
      composition of spores upon germination in response to environmental changes. In
      addition, we investigated the effects of different compounds on this process.
      Agents and environmental conditions inducing germination were characterized
      monitoring changes in optical density (OD). Among all tested conditions, the
      greatest drop in OD(625) (57.4%) was obtained when spores were incubated in l
      alanine/l-lactate buffer, pH 4.6. In addition, a carbon-coating SEM technique and
      X-ray microanalysis were used to observe the architecture of spores and to
      examine calcium dipicolinate release. Conditions inducing C. tyrobutyricum spore
      germination were identified and SEM X-ray microanalysis clearly distinguished
      germinating from dormant spores. We confirmed that calcium dipicolinate release
      is one of the first events occurring. These microscopy methods could be
      considered sensitive tools for evaluating morphological and chemical changes in
      spores of C. tyrobutyricum during the initial phase of germination. Information
      gathered from this work may provide new data for further research on germination.

PMID- 19393741
TI  - Protein folding in Escherichia coli: the chaperonin GroE and its substrates.
AB  - A brief summary of the role of DnaK and GroE chaperones in protein folding
      precedes a discussion of the role of GroE in Escherichia coli. We consider its
      obligate substrates, the 8 that are both obligate and essential, and the
      prospects for constructing a mutant that could survive without it. Structural
      features of GroE-dependent polypeptides are also considered.

PMID- 19393742
TI  - Reciprocal regulation of the bile acid-activated receptor FXR and the interferon
      gamma-STAT-1 pathway in macrophages.
AB  - Nuclear receptors are a family of ligand regulated factors that exert homeostatic
      functions at the interface between metabolic and immune function. The farnesoid X
      receptor (FXR) is a bile acid sensor expressed in immune cells such as
      macrophages where it exerts counter-regulatory effects. FXR deficient mice
      demonstrate disregulated immune response. Expression of FXR is down-regulated in
      inflamed tissues but the mechanism that leads to FXR down-regulation by
      inflammatory mediators is unknown. In the present study we have investigated the
      effect of inflammation-related cytokines on macrophages and demonstrated that
      INFgamma is a potent inhibitor of FXR gene expression/function in macrophages.
      STAT1 silencing and over-expression experiments demonstrated that FXR repression
      is mediated by INFgamma dependent activation of STAT1. Since IFNgamma is a potent
      activator of STAT1 we searched for STAT1 binding sites in the human FXR genomic
      and identified a region of the human FXR gene between the second and third exon
      that contains three hypothetical STAT1 binding sites. RAW 264.7 transiently
      transfected with an FXR genomic reporter construct which contained the three STAT
      binding sites responded to IFNgamma with a robust decrease in the reporter
      activity, demonstrating the potent modulation of FXR transcription by IFNgamma.
      Chromatin immunoprecipitation assay revealed that this region was
      immunoprecipitated following treatment of macrophage cell lines and supershift
      assay demonstrated that STAT1 was able to bind one of three identified sites. In
      summary, these results suggest that IFNgamma induced STAT1 homodimers modulate
      the transcriptional repression of FXR gene in macrophages during inflammation
      related cytokines.

PMID- 19393743
TI  - WITHDRAWN: Introduction to a Special Issue of Neuroimage on Brain-Body Medicine.
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- 19393745
TI  - Brain pathways of verbal working memory: a lesion-function correlation study.
AB  - Working memory relies on information processing by several well-identified gray
      matter regions. However, the white matter regions and pathways involved in this
      cognitive process remain unknown. An attractive and underexplored approach to
      study white matter connectivity in cognitive functions is through the use of non
      aprioristic models, which specifically search disrupted white matter pathways.
      For this purpose, we used voxel-based lesion-function mapping to correlate white
      matter lesions on the magnetic resonance images of 54 multiple sclerosis patients
      with their performance on a verbal working memory task. With this approach, we
      have identified critical white matter regions involved in verbal working memory
      in humans. They are located in the cingulum, parieto-frontal pathways and thalamo
      cortical projections, with a left-sided predominance, as well as the right
      cerebellar white matter. Our study provides direct evidence on the white matter
      pathways subserving verbal working memory in the human brain.

PMID- 19393746
TI  - Multi-locus phylogeny of the family Acrocephalidae (Aves: Passeriformes)--the
      traditional taxonomy overthrown.
AB  - We present the first study of the warbler family Acrocephalidae based on one
      mitochondrial and three nuclear DNA loci, in total approximately 2900 bp,
      including most or all of the species in three (Acrocephalus, Hippolais and
      Chloropeta) of the four genera and one species in the fourth genus (Nesillas) in
      this family. All three genera were suggested to be non-monophyletic, although the
      non-monophyly of Acrocephalus is not fully convincingly demonstrated. Six major
      clades were found, which agreed largely with the results from two earlier
      mitochondrial studies, and for which the names Hippolais, Iduna, Acrocephalus,
      Calamocichla, Notiocichla and Calamodus have been used. However, the results also
      revealed some new constellations, due to better resolution of deeper nodes and
      the inclusion of more taxa. The taxonomic implications are discussed.

PMID- 19393744
TI  - Linking functional and structural brain images with multivariate network
      analyses: a novel application of the partial least square method.
AB  - In this article, we introduce a multimodal multivariate network analysis to
      characterize the linkage between the patterns of information from the same
      individual's complementary brain images, and illustrate its potential by showing
      its ability to distinguish older from younger adults with greater power than
      several previously established methods. Our proposed method uses measurements
      from every brain voxel in each person's complementary co-registered images and
      uses the partial least square (PLS) algorithm to form a combined latent variable
      that maximizes the covariance among all of the combined variables. It represents
      a new way to calculate the singular value decomposition from the high-dimensional
      covariance matrix in a computationally feasible way. Analyzing fluorodeoxyglucose
      positron emission tomography (PET) and volumetric magnetic resonance imaging
      (MRI) images, this method distinguished 14 older adults from 15 younger adults
      (p=4e-12) with no overlap between groups, no need to correct for multiple
      comparisons, and greater power than the univariate Statistical Parametric Mapping
      (SPM), multimodal SPM or multivariate PLS analysis of either imaging modality
      alone. This technique has the potential to link patterns of information among any
      number of complementary images from an individual, to use other kinds of
      complementary complex datasets besides brain images, and to characterize
      individual state- or trait-dependent brain patterns in a more powerful way.

PMID- 19393747
TI  - Light-induced and apoptosis-like cell death in the unicellular eukaryote,
      Blepharisma japonicum.
AB  - The unicellular eukaryote, Blepharisma japonicum, is a light-sensitive ciliated
      protozoa. It possesses a photoreceptor pigment called blepharismin that plays
      critical roles in defensive behavior against predators and step-up photophobic
      response. In addition, the pigment generates reactive oxygen species such as
      singlet oxygen and hydroxyl radicals which contribute to photodynamic action.
      Previous studies reported that intense light (>300W m(-2)) induced rapid
      photodynamic killing (necrosis) characterized by cell swelling and plasma efflux,
      while moderate light (3-30W m(-2)) only induced pigment extrusion and
      photooxidation. We have found that moderate light (5W m(-2)) induced apoptosis
      like cell death. Microscopically it was found that >3h of moderate light
      irradiation induced macronuclear condensation and plasma efflux without cell
      swelling. Single cell gel electrophoresis assay showed that DNA fragmentation
      occurred between 1 and 3h of irradiation, and the condensed macronuclei contained
      quite fragmented DNA. Macronuclear DNA extracted from light-irradiated cells
      contained DNA fragments of 180-200 and 360-400bp, which were seen as apoptosis
      ladders.

PMID- 19393748
TI  - Differential expression of Dicer and Argonaute genes during the differentiation
      of human neuroblastoma cells.
AB  - Dicer and Argonaute 1-4 proteins are key components of the cytoplasmic enzyme
      machinery responsible for biogenesis and performance of microRNAs. To gain
      insight into the roles of these proteins in cell differentiation, we investigated
      possible changes in the expression levels of Dicer and Argonaute 1-4 genes during
      the differentiation of cultured neural and glial cells. The results show that the
      5 genes are differentially expressed along the 2 differentiation pathways and
      suggest a prevalent role of Dicer and Argonaute 4 in neural cell differentiation.

PMID- 19393749
TI  - A pea mutant (costata) expressing higher activity in thylakoid membrane-bound
      carbonic anhydrase alters PSII downregulation mechanisms.
AB  - The interaction between photosynthetic electron transport and the activities of
      the thylakoid associated carbonic anhydrase (tCA), estimated as combined tCA
      activity in pea plants (Pisum sativum L. Borek cv., WT) and mutant form (costata
      2/125) that differ in chlorophyll content have been compared. Chlorophyll a
      fluorescence changes after the inhibition of tCA by ethoxyzolamide (EZ),
      estimating possible role of tCA in PSII downregulation were investigated. Costata
      expresses higher tCA activity and higher O2 evolution in comparison to WT.
      Inhibition of tCA by EZ decreased effective PSII photochemistry that coincided
      with an enhancement in thermal dissipation, while maximal PSII quantum yield
      (F(v)/F(m)) did not significantly change. Ethoxyzolamide induced changes in
      fluorescence parameters that were more strongly expressed in costata 2/125. The
      results show that tCA is involved in the regulation of the proton gradient across
      thylakoid membranes and thus limits PSII downregulation.

PMID- 19393750
TI  - Effect of silicon dioxide on expression of poly (ADP-ribose) polymerase mRNA and
      protein.
AB  - Silicon dioxide induces acute injury and chronic pulmonary fibrosis.
      International Agency for Research on Cancer (IARC) listed it as a human
      carcinogen in 1996. However, the molecular mechanisms to induce cancer are not
      understood yet. The content of poly (ADP-ribose) polymerases (PARP) mRNA and
      protein in Hela cells treated with concentrations of silicon dioxide up to
      400microg/ml was determined by real-time fluorogenetic quantitative PCR (RQ-PCR)
      and immunofluorescence assay, respectively. MTT assay was used to determine cell
      viability. The results showed that viability at 400microg/ml silica was
      significantly decreased but not at lower concentrations. The protein content of
      gamma-H2AX in silica-treated group was significantly higher than the controls.
      The PARP mRNA and protein levels were significantly reduced with a dose response
      manner from the lowest silicon dioxide level. Our findings suggested that silicon
      dioxide increased the expression of gamma-H2AX and inhibited the expression of
      PARP mRNA and protein in Hela cells.

PMID- 19393751
TI  - Corneal epithelial-like transdifferentiation of hair follicle stem cells is
      mediated by pax6 and beta-catenin/Lef-1.
AB  - Several types of adult stem cells are capable of transdifferentiaton into other
      types of tissues. The hair follicle bulge area is an abundant and easily
      accessible source of pluripotent adult stem cells. We demonstrate that the bulge
      KSCs have the potential for transdifferentiation into corneal epithelial-like
      cells. Bulge KSCs isolated by collagen type IV adhesiveness possessed the highest
      colony formation efficiency (CFE), and expressed specific markers (CD34 and
      alpha6-integrin). The isolated cells transdifferentiate into corneal epithelial
      like cells in conditioned medium containing corneal limbus soluble factors,
      including their specific marker, keratin12. The transdifferentiation depends on
      upregulation of pax6 and downregulation of beta-catenin and Lef-1. Furthermore,
      overexpression of pax6 in bulge KSCs induced their expression of k12. The
      expressions of beta-catenin and Lef-1 were not suppressed in the pax6-transfected
      bulge KSCs, but which were downregulated pax6-transfected cells cultured in the
      conditioned medium. Bulge KSCs may have potential therapeutic application as cell
      source for the construction of bioengineered corneas.

PMID- 19393752
TI  - Background ELF magnetic fields in incubators: a factor of importance in cell
      culture work.
AB  - Extremely low frequency (ELF) magnetic fields in cell culture incubators have
      been measured. Values of the order of tens of muT were found which is in sharp
      contrast to the values found in our normal environment (0.05-0.1microT). There
      are numerous examples of biological effects found after exposure to MF at these
      levels, such as changes in gene expression, blocked cell differentiation,
      inhibition of the effect of tamoxifen, effects on chick embryo development, etc.
      We therefore recommend that people working with cell culture incubators check for
      the background magnetic field and take this into account in performing their
      experiments, since this could be an unrecognised factor of importance
      contributing to the variability in the results from work with cell cultures.

PMID- 19393753
TI  - Effect of FK506 and cyclosporine A on the expression of BDNF, tyrosine kinase B
      and p75 neurotrophin receptors in astrocytes exposed to simulated ischemia in
      vitro.
AB  - We investigated whether the immunosuppressive drugs, FK506 and cyclosporine A,
      increase BDNF protein and/or mRNA expression in ischemic astrocytes and if an
      increase could be related to changes in the nuclear expression of p-CREB, p
      Erk1/2 and p-Akt. The influence of these immunosuppressants on protein and mRNA
      levels of TrkB and p75(NTR) receptors was also examined. On day 21, cultures of
      rat astrocytes were subjected to ischemic conditions simulated in vitro (combined
      oxygen glucose deprivation, OGD) for 8h and exposed to FK506 (10-1000nM) and
      cyclosporine A (0.25-10microM). FK506 and cyclosporine A (at 1000nM and
      0.25microM, respectively) stimulated the expression and release of BDNF in
      cultured rat cerebral cortical astrocytes exposed to OGD. The immunosuppressants
      at these doses simultaneously increased p-CREB and p-Erk1/2 expression in the
      nuclear fraction of astrocytes. The results RT-PCR and Western blot analysis
      provided further evidence of a modulating influence of the drugs on the
      expression of trkB and p75(NTR) genes and their protein products in ischemic
      astrocytes.

PMID- 19393754
TI  - Three key variables involved in feeder preparation for the maintenance of human
      embryonic stem cells.
AB  - Although the development of a feeder-free culture system for future applications
      of human embryonic stem cells (hESCs), at present the regular culture system uses
      mitotically inactivated mouse embryonic fibroblasts (mEFs) as feeder cells for
      maintaining undifferentiated hESCs. Mitomycin C (MMC) is used to inactivate mEFs,
      but this causes DNA damage, and it is unclear whether MMC remains in the culture
      system after several washes. Three variables have been evaluated with respect to
      feeder preparation and MMC involvement, including mEF exposure to MMC, density of
      feeder cells, and different wash steps during the preparation of feeder cells.
      These variables are critical to the subsequent planting of hESCs because remnants
      of MMC would be unsafe with respect to long-term culture of hESCs The novel data
      here evaluates the remnant amounts of MMC in a hESCs culture system using
      HPLC/MS/MS. The ultimate objective of this study is the control of MMC within a
      safe range.

PMID- 19393755
TI  - Comparison of murine dental follicle precursor and retinal progenitor cells after
      neural differentiation in vitro.
AB  - Human dental stem or precursor cells can differentiate into multiple cell types
      like adipocytes, osteoblasts or chondrocytes. Recently, a number of different
      human dental stem cell lines were differentiated into neurons. This makes dental
      stem cells interesting as possible cell-based therapeutics for neural
      degenerative diseases. To test this hypothesis, we have investigated the neural
      differentiation potential of murine dental follicle precursor cells (mDFPCs). The
      mDFPC cell line was newly established without cell immortalization. After
      differentiation, neural cell marker expression in mDFPCs was checked and compared
      with that of murine retinal progenitor cells (mRPCs). Differentiated mDFPCs
      became neuron-like cells with small cell bodies and long/branching neurites,
      similar to differentiated mRPCs. However, mRPCs showed more complete neural
      differentiation. Furthermore, 5% of the differentiated mDFPCs and 37% of the
      differentiated mRPCs were positive for the glia cell marker GFAP (glial
      fibrillary acidic protein). The data presents new evidence of neural
      differentiation of mDFPCs, but only a small percentage of mDFPCs differentiated
      into glia cells, unlike mRPCs.

PMID- 19393757
TI  - Evidence of a Ca(2+)-(*)NO-cGMP signaling pathway controlling zoospore biogenesis
      in the aquatic fungus Blastocladiella emersonii.
AB  - The sporulation stage of the aquatic fungus Blastocladiella emersonii culminates
      with the formation and release to the medium of a number of zoospores, which are
      motile cells responsible for the dispersal of the fungus. The presence in the
      sporulation solution of 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a
      potent and selective inhibitor of nitric oxide-sensitive guanylyl cyclases,
      completely prevented biogenesis of the zoospores. In addition, this compound was
      able to significantly reduce cGMP levels, which increase drastically during late
      sporulation, suggesting the existence of a nitric oxide-dependent mechanism for
      cGMP synthesis. Furthermore, increased levels of nitric oxide-derived products
      were detected during sporulation by fluorescence assays using DAF-2 DA, whose
      signal was drastically reduced in the presence of the nitric oxide synthase
      inhibitor Nomega-Nitro-L-arginine methyl ester (L-NAME). These results were
      confirmed by quantitative chemiluminescent determination of the intracellular
      levels of nitric oxide-derived products. A putative nitric oxide synthase (NOS)
      activity was detected throughout sporulation, and this enzyme activity decreased
      significantly when L-NAME and 1-[2-(Trifluoromethyl)phenyl]imidazole (TRIM) were
      added to the assays. NOS assays carried out in the presence of EGTA showed
      decreased enzyme activity, suggesting the involvement of calcium ions in enzyme
      activation. Additionally, expressed sequence tags (ESTs) encoding putative
      guanylyl cyclases and a cGMP-phosphodiesterase were found in B. emersonii EST
      database (http://blasto.iq.usp.br), and the mRNA levels of the corresponding
      genes were observed to increase during sporulation. Altogether, data presented
      here revealed the presence and expression of guanylyl cyclase and cGMP
      phosphodiesterase genes in B. emersonii and provided evidence of a Ca(2+)-(*)NO
      cGMP signaling pathway playing a role in zoospore biogenesis.

PMID- 19393758
TI  - Identification of specific binding sites for XYR1, a transcriptional activator of
      cellulolytic and xylanolytic genes in Trichoderma reesei.
AB  - The transcriptional activator XYR1 is the central regulator that governs
      cellulolytic and xylanolytic gene expression in Trichoderma reesei. However,
      despite its biological importance, relatively little is known about its
      functional binding sequences. In the present study, we investigated the binding
      characteristics and specific target for XYR1 by using DNase I footprinting
      analysis and electrophoretic mobility shift assays. We demonstrate that XYR1 can
      interact not only with the 5'-GGCTAA-3' motif but also with several 5'
      GGC(A/T)(3)-3' motifs. In silico analysis revealed that the 5'-GGC(A/T)(3)-3'
      motifs are widespread as single site in 5'-upstream region of all the XYR1
      regulated genes. Furthermore, we defined the important nucleotides within the
      binding site that contribute to specific interaction with XYR1. Our results
      suggest that, together with the inverted repeat motifs, the single 5'-GGC(A/T)(4)
      3' motifs play important roles as functional XYR1-binding sites in the regulation
      of cellulase and xylanase gene expression in T. reesei.

PMID- 19393759
TI  - Animal models of airway inflammation and airway smooth muscle remodelling in
      asthma.
AB  - Asthma is a complex disease that involves chronic inflammation and subsequent
      decline in airway function. The widespread use of animal models has greatly
      contributed to our understanding of the cellular and molecular pathways
      underlying human allergic asthma. Animal models of allergic asthma include
      smaller animal models which offer 'ease of use' and availability of reagents, and
      larger animal models that may be used to address aspects of allergic airways
      disease not possible in humans or smaller animal models. This review examines the
      application and suitability of various animal models for studying mechanisms of
      airway inflammation and tissue remodelling in allergic asthma, with a specific
      focus on airway smooth muscle.

PMID- 19393760
TI  - Bio-Mos: an effective inducer of dicentracin gene expression in European sea bass
      (Dicentrarchus labrax).
AB  - Concern over the use of dietary antibiotics in aquaculture has encouraged the
      industry to search for alternatives that both enhance performance and afford
      protection from disease. Bio-Mos, derived from the outer cell wall of a specific
      strain of yeast Saccharomyces cerevisiae (Alltech Inc, USA) is a product that
      fits these criteria. Here, we present data on the impact of a Bio-Mos
      supplemented diet on the mRNA copy number of the antimicrobial peptide
      dicentracin, whose transcript regulation has not yet been explored in fish.We
      analyzed Bio-Mos-induced changes in the expression of sea bass (Dicentrarchus
      labrax) dicentracin,using a one-tube two-temperature real-time RT-PCR with which
      the gene expression can be absolutely quantified using the standard curve method.
      Our results revealed that 30 days of feeding fish with diets containing Bio-Mos
      supplemented at either 3 per thousand or 5 per thousand significantly increased
      the dicentracin mRNA copy number in the head kidney. Furthermore, the mRNA copy
      number in fish fed at 3 per thousand was significantly higher than that of the
      group fed at 5 per thousand for the same period of feeding Bio-Mos. A longer
      feeding period (60 days)did not further increase the dicentracin transcript
      levels as compared to the values recorded after 30 days of feeding either in the
      group fed at 3 per thousand or in the one fed at 5 per thousand diet. However,
      the transcript levels in fish fed at 3 per thousand proved to be significantly
      higher than those of the controls after 60 days of feeding. These findings offer
      new information about the response of antimicrobial peptides at the
      transcriptional level to diets supplemented with immune response modulators, and
      support a role of Bio-Mos in promoting sea bass nonspecific immune system.

PMID- 19393761
TI  - Opening the doors to cytochrome c: changes in mitochondrial shape and apoptosis.
AB  - Mitochondria are key organelles in the regulation of apoptosis induced by
      intrinsic stimuli. This is accomplished by the release in the cytoplasm of
      cytochrome c and of other cofactors that ensure the activation of effector
      caspases. Multiple changes in the shape of the organelle occur around the time of
      the release of these factors, including fragmentation of the mitochondrial
      network and the activation of the so-called "cristae remodeling" pathway.
      However, contrasting evidence exist on the functional role of these changes. Here
      we review the molecular mechanisms that control mitochondrial shape, their
      changes during apoptosis and the role that these changes might play in the
      amplification of the apoptotic cascade.

PMID- 19393756
TI  - Fermented liquid feed enhances bacterial diversity in piglet intestine.
AB  - Because of limitations imposed on the antibiotic use in animal industry, there is
      a need for alternatives to maintain the efficiency of production. One of them may
      be the use of fermented liquid feed (FLF) but how it affects gut ecology is
      poorly understood. We investigated the effect of three diets, standard dry feed
      (control), dry feed supplemented with antibiotics, and fermented liquid feed
      (FLF, fermented with Lactobacillus plantarum), on gut bacterial diversity in
      piglets. The structure of the ileal and caecal communities was estimated by
      sequencing the SSU rRNA gene libraries. Antibiotic-supplemented feed slightly
      increased bacterial diversity in the ileum but reduced it in the caecum while in
      FLF-fed animals bacterial diversity was elevated. The majority of bacterial
      sequences in the ileum of all three groups belonged to lactobacilli (92-98%). In
      the caecum the lactobacilli were still dominant in control and antibiotic-fed
      animals (59% and 64% of total bacterial sequences, respectively) but in FLF-fed
      animals they fell to 31% with the concomitant increase in the Firmicutes
      diversity represented by the Dorea, Coprococcus, Roseburia and Faecalibacterium
      genera. Thus FLF affects the gut ecology in a different way than antibiotics and
      contributes to the enhanced bacterial diversity in the gastrointestinal tract.

PMID- 19393762
TI  - Spread and evolution of Plasmodium falciparum drug resistance.
AB  - Worldwide spread of Plasmodium falciparum drug resistance to conventional
      antimalarials, chloroquine and sulfadoxine/pyrimethamine, has been imposing a
      serious public health problem in many endemic regions. Recent discovery of drug
      resistance-associated genes, pfcrt, pfmdr1, dhfr, and dhps, and applications of
      microsatellite markers flanking the genes have revealed the evolution of parasite
      resistance to these antimalarials and the geographical spread of drug resistance.
      Here, we review our recent knowledge of the evolution and spread of parasite
      resistance to chloroquine and sulfadoxine/pyrimethamine. In both antimalarials,
      resistance appears to be largely explained by the invasion of limited resistant
      lineages to many endemic regions. However, multiple, indigenous evolutionary
      origins of resistant lineages have also been demonstrated. Further molecular
      evolutionary and population genetic approaches will greatly facilitate our
      understanding of the evolution and spread of parasite drug resistance, and will
      contribute to developing strategies for better control of malaria.

PMID- 19393763
TI  - Avian phospholipid transfer protein causes HDL conversion without affecting
      cholesterol efflux from macrophages.
AB  - Circulatory phospholipid transfer protein (PLTP) has two major functions: 1)
      transfer of phospholipids towards HDL particles; and 2) modulation of HDL size
      and composition via the HDL conversion process. In the laying hen (Gallus
      gallus), the massive oocyte-targeted lipid flow is achieved through the concerted
      actions of lipases, lipid transfer proteins, and relatives of the LDL receptor
      family. The aim of the study was to gain insights into the structure and
      functions of chicken PLTP. The results demonstrate that PLTP is highly conserved
      from chicken to mammals, as (i) chicken PLTP is associated with plasma HDL; (ii)
      it clearly possesses phospholipid transfer activity; (iii) it is inactivated at
      +58 degrees C; and (iv) it mediates conversion of avian and human HDL into small
      prebeta-mobile HDL and large fused alpha-mobile HDL particles. Our data show that
      HDL from different chicken models is similar in chemical and physical properties
      to that of man based on PLTP activity, cholesterol efflux, and HDL conversion
      assays. In contrast to mammals, PLTP-facilitated HDL remodeling did not enhance
      cholesterol efflux efficiency of chicken HDL particles.

PMID- 19393764
TI  - Emotional recognition in depressed epilepsy patients.
AB  - The current study examined the relationship between emotional recognition and
      depression using the Minnesota Multiphasic Personality Inventory, Second Edition
      (MMPI-2), in a population with epilepsy. Participants were a mixture of surgical
      candidates in addition to those receiving neuropsychological testing as part of a
      comprehensive evaluation. Results suggested that patients with epilepsy reporting
      increased levels of depression (Scale D) performed better than those patients
      reporting low levels of depression on an index of simple facial recognition, and
      depression was associated with poor prosody discrimination. Further, it is
      notable that more than half of the present sample had significantly elevated
      Scale D scores. The potential effects of a mood-congruent bias and implications
      for social functioning in depressed patients with epilepsy are discussed.

PMID- 19393765
TI  - The sign of the cross as a learned ictal automatism?
AB  - Described here is a case of a patient who made the sign of the cross during right
      mesial temporal seizures, documented by intracranial depth electrode and
      simultaneous scalp video-EEG. The patient was ultimately found to have
      predominantly left temporal lobe epilepsy, and she was rendered seizure free for
      many years following a left anterior temporal lobe resection. Most interestingly,
      however, was a suggestion that in her case, making the sign of the cross may have
      represented a learned ictal behavioral phenomenon: the patient had been forced,
      over a period of many years, to make this gesture as an atonement in the
      postictal period. The movement ultimately came to be performed unconsciously,
      during the ictus, associated with a lateralized seizure discharge in the right
      temporal lobe. In contrast to seizure-induced experiential phenomena and typical
      motor automatisms, where the behavioral manifestations have no recognized
      association with learning, we wondered whether the pathophysiological mechanisms
      of chronic focal epilepsy had subserved in this case a psychological learning
      process, whereby right temporal seizures were ultimately able to recruit and
      activate an adjacent neural memory circuit.

PMID- 19393766
TI  - Epilepsy and behavior. Introduction.

PMID- 19393767
TI  - Endocrine disruptors modulate expression of hepatic choriogenin genes in the
      hermaphroditic fish, Kryptolebias marmoratus.
AB  - Choriogenins (Chgs) are precursors of inner layer of egg envelope that are
      synthesized in fish liver in response to estrogens. Therefore, study of their
      expression serves as biomarker of exposure to endocrine disrupting chemicals
      (EDCs). The self-fertilizing fish, Kryptolebias marmoratus has been established
      as a model species for testing the action of EDCs. To use this fish as a model
      for assessing estrogenic activity of EDCs on Chg expression, two K. marmoratus
      choreogenin genes, Km-ChgH and Km-ChgL were cloned and their expression was
      analyzed in different tissues and in developmental stages by real-time RT-PCR.
      Expression levels of liver mRNA were compared between hermaphrodites and
      secondary males after exposure to EDCs. Km-ChgH and Km-ChgL genes that were
      predominantly expressed in liver contained zona pellucida (ZP) domains. During
      embryonic development, low expression of mRNA was observed at stage 1 (2 dpf)
      that reached highest level at stage 4 (12 dpf) or stage 5 (5 h post hatching).
      The expression of Km-Chg mRNAs was highly increased in liver exposed to natural
      estrogen, 17alpha-estradiol (E2) as well as EDCs such as bisphenol A and 4-n
      nonylphenol in both the gender types. Another EDC, 4-tert-octylphenol, showed
      modulatory effect only on Km-ChgH in hermaphrodites. Tamoxifen, an antagonist of
      the estrogen receptor showed no effect on expression of Chg genes in either of
      the gender types of K. marmoratus. These findings indicate that Km-Chg genes
      would be associated with estrogen and measurement of their expression would serve
      as a surrogate biomarker of exposure to environmental EDCs.

PMID- 19393768
TI  - An assessment of the understanding and motivations of patients with schizophrenia
      about participating in a clinical trial.
AB  - Enrollment of an adequate number of subjects for a clinical trial is a perennial
      challenge and this might arguably be even more difficult and complex in trials
      involving patients with schizophrenia. In this paper, we used a modification of
      the Prospective Preference Approach (PPA) as a prelude to an actual randomized
      placebo-controlled trial of a cognitive-enhancing agent for patients with
      schizophrenia. This approach sought to test and enhance subjects' understanding
      of the key concepts of the trial, and administered the PPA at baseline and
      following a brief educational module. The motivations and concerns regarding
      potential participation in the proposed trial were also elicited by the PPA. Of
      one hundred ninety patients with schizophrenia recruited for this PPA study, only
      12 (6.3%) were assessed to have understood all key trial-related concepts after
      the initial explanation and baseline PPA administration (prior to the educational
      module). Following the education module, however, there was significant increase
      in the number of patients who understood all key trial elements. Younger age and
      higher level of education were significant factors associated with better
      understanding of the proposed trial. The main reasons cited for wishing to
      participate in clinical trials were personal medical benefits and altruistic
      desire to help others. Concerns regarding the safety of the trial medication were
      expressed in over 80% of the subjects. PPA administration with educational module
      supplementation may provide a valuable addition to clinical trial procedures in
      patients with schizophrenia.

PMID- 19393769
TI  - Crosses prior to parthenogenesis explain the current genetic diversity of
      tropical plant-parasitic Meloidogyne species (Nematoda: Tylenchida).
AB  - The tropical and subtropical parthenogenetic plant-parasitic nematodes
      Meloidogyne are polyphagous major agricultural pests. Implementing proper pest
      management approaches requires a good understanding of mechanisms, population
      structure, evolutionary patterns and species identification. A comparative
      analysis of the mitochondrial vs nuclear diversity was conducted on a selected
      set of Meloidogyne lines from various geographic origins. Mitochondrial co2-16S
      sequences and AFLP markers of total DNA were applied because of their ability to
      evidence discrete genetic variation between closely related isolates. Several
      distinct maternal lineages were present, now associated with different genetic
      backgrounds. Relative discordances were found when comparing mitochondrial and
      nuclear diversity patterns. These patterns are most likely related to crosses
      within one ancestral genetic pool, followed by the establishment of
      parthenogenesis. In this case, they mirror the genetic backgrounds of the
      original individuals. Another aspect could be that species emergence was recent
      or on process from this original genetic pool and that the relatively short time
      elapsed since then and before parthenogenesis settlement did not allow for
      lineage sorting. This could also be compatible with the hypothesis of hybrids
      between closely related species. This genetic pool would correspond to a species
      as defined by the species interbreeding concept, but also including the grey area
      of species boundaries. This complex process has implications on the way genotypic
      and phenotypic diversity should be addressed. The phenotype of parthenogenetic
      lines is at least for part determined by the ancestral amphimictic genetic
      background. A direct consequence is, therefore, in terms of risk management, the
      limited confidence one can have on the direct association of an agronomic threat
      to a simple typing or species delineation. Risk management strategies and tools
      must thus consider this complexity when designing quarantine implementation,
      resistance breeding programmes or molecular diagnostic.

PMID- 19393770
TI  - Population structure, origins and evolution of major Salmonella enterica clones.
AB  - The genus Salmonella consists of two species S. enterica and S. bongori. S.
      enterica has a well defined subspecies structure with seven subspecies
      consistently delineated by sequence variation. Frequency of recombination between
      subspecies and within a subspecies is markedly different. Subspecies I undergoes
      frequent recombination as demonstrated recently, demystifying the long-held
      belief that Salmonella is a highly clonal organism. The majority of disease
      causing serovars are from subspecies I with the most important serovars in human
      health being Typhimurium and Typhi. Typhimurium has developed considerable
      diversity and may be a very old serovar. The majority of the isolates belong to a
      single clonal complex by multilocus sequence typing. Typhimurium isolates are
      divided into phage types and some of the phage types do not have a single origin
      as determined using mutational changes. Phage type DT104 is heterogeneous and
      represented in multiple sequence types, with its multidrug-resistant variant most
      successful causing epidemics in many parts of the world. Typhi, a human
      restricted serovar, is relatively young compared to Typhimurium, and has a low
      level of sequence variation. Single nucleotide polymorphisms (SNPs) have been
      shown to be very useful for typing and resolving relationships within Typhi.
      Genome sequences of 19 isolates revealed more than 1700 SNPs. The fully resolved
      phylogenetic tree allows one to trace the mutational changes occurred during
      clonal diversification. Genome wide SNPs have greatly enhanced our understanding
      of the evolution of Salmonella clones.

PMID- 19393771
TI  - A proposal for new criteria for the classification of hantaviruses, based on S
      and M segment protein sequences.
AB  - Hantaviruses, members of the family Bunyaviridae, are the causative agents of
      hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome.
      Hantaviruses are currently demarcated into species based on the guidelines
      provided by the International Committee on Taxonomy of Viruses (ICTV). These
      guidelines however, are often ignored by the descriptors of novel hantaviruses.
      With this study we attempted to refine the second ICTV guideline for hantavirus
      species demarcation by phylogenetically analyzing all in Genbank available
      complete sequences derived from the S, M or L segments of hantaviruses. S and M
      segment amino acid sequence comparison allowed clear and unequivocal distinction
      between different hantavirus species, and lead us to propose additional criteria
      for the demarcation of hantavirus species (S segment amino acid distance >10% or
      M segment amino acid distance >12%) and hantavirus groups (S segment amino
      distance >24% or M segment amino acid distance >32%). With this study, we propose
      to adjust the second rule of the ICTV classification guidelines ("a 7% difference
      in amino acid identity when comparing the complete S segment and M segment
      sequences") to a more appropriate rule, "a 10% difference in S segment similarity
      and a 12% difference in M segment similarity based on complete amino acid
      sequences" in accordance with the current situation in the hantavirus field.

PMID- 19393772
TI  - Extensive survey on the prevalence and genetic diversity of SIVs in primate
      bushmeat provides insights into risks for potential new cross-species
      transmissions.
AB  - To evaluate the risk of cross-species transmissions of SIVs from non-human
      primates to humans at the primate/hunter interface, a total of 2586 samples,
      derived from primate bushmeat representing 11 different primate species, were
      collected at 6 distinct remote forest sites in southeastern Cameroon and in
      Yaounde, the capital city. SIV prevalences were estimated with an updated SIV
      lineage specific gp41 peptide ELISA covering the major part of the SIV diversity.
      SIV positive samples were confirmed by PCR and sequence analysis of partial pol
      fragments. The updated SIV ELISA showed good performance with overall sensitivity
      and specificity of 96% and 97.5% respectively. The overall SIV seroprevalence was
      low, 2.93% (76/2586) and ranged between 0.0% and 5.7% at forest sites, and
      reached up to 10.3% in Yaounde. SIV infection was documented in 8 of the 11
      species with significantly different prevalence rates per species: 9/859 (1.0%)
      in Cercopithecus nictitans, 9/864 (1.0%) Cercopithecus cephus, 10/60 (16.7%)
      Miopithecus ogouensis, 14/78 (17.9%) Colobus guereza, 15/37 (40.5%) Cercopithecus
      neglectus, 10/27 (33.3%) Mandrillus sphinx, 6/12 (50%) Cercocebus torquatus, and
      3/6 (50%) Chlorocebus tantalus. No SIV infection was identified in Cercopithecus
      pogonias (n=293), Lophocebus albigena (n=168) and Cercocebus agilis (n=182). The
      SIV prevalences also seem to vary within species according to the sampling site,
      but most importantly, the highest SIV prevalences are observed in the primate
      species which represent only 8.5% of the overall primate bushmeat. The
      phylogenetic tree of partial pol sequences illustrates the high genetic diversity
      of SIVs between and within different primate species. The tree also showed some
      interesting features within the SIVdeb lineage suggesting phylogeographic
      clusters. Overall, the risk for additional cross-species transmissions is not
      equal throughout southern Cameroon and depends on the hunted species and SIV
      prevalences in each species. However, humans are still exposed to a high
      diversity of SIVs as illustrated by the high inter and intra SIV lineage genetic
      diversity.

PMID- 19393773
TI  - Chlorogenic acid inhibits lipopolysaccharide-induced cyclooxygenase-2 expression
      in RAW264.7 cells through suppressing NF-kappaB and JNK/AP-1 activation.
AB  - Chlorogenic acid (CGA) is a naturally occurring phenolic acid in human diet. Data
      obtained from in vivo and in vitro experiments demonstrate that CGA mostly
      presents anti-oxidant and anti-carcinogenic activities. Here we show that CGA
      also inhibits lipopolysaccharide (LPS)-induced inflammatory response[AU1] in RAW
      264.7 cells. Our results indicated that CGA significantly decreased LPS-induced
      up-regulation of cyclooxygenase (COX-2) at protein and mRNA levels in RAW 264.7
      cells and as a result it inhibited prostaglandin E(2) (PGE(2)) release from LPS
      treated RAW 264.7 cells. In the further experiments, LPS-induced activation of
      nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK)-c-Jun
      activator protein (AP-1) pathway were suppressed significantly by CGA. In
      addition, CGA did not affect phosphorylation of extracellular signal-regulated
      kinase 1/2 (ERK1/2) and p38. In conclusion, CGA suppresses LPS-induced COX-2
      expression via attenuating the activation of NF-kappaB and JNK/AP-1 signaling
      pathways suggesting that CGA, the polyphenol compound in our food, could exert
      anti-inflammatory effects through inhibiting PGE(2) production.

PMID- 19393774
TI  - Amlodipine inhibits TNF-alpha production and attenuates cardiac dysfunction
      induced by lipopolysaccharide involving PI3K/Akt pathway.
AB  - Calcium channel blockers (CCBs) are widely used in the therapy of cardiovascular
      diseases. Recent studies have shown that several CCBs exerted distinct anti
      inflammatory effect in myocardial dysfunction models. The purpose of the present
      study was to evaluate therapeutic effect and possible mechanism of action of
      amlodipine, one of the widely used CCBs, on rat cardiac dysfunction during sepsis
      induced by lipopolysaccharide (LPS). Pretreatment of the rats with amlodipine (10
      or 30 mg/kg, i.v.) delayed the fall of mean arterial blood pressure caused by
      LPS. Amlodipine also significantly inhibited the elevation of plasma tumor
      necrosis factor alpha (TNF-alpha) and decreased levels of inducible nitric oxide
      synthase (iNOS) in response to LPS challenge. To investigate the mechanism of the
      action of amlodipine, neonatal rat cardiomyocytes were used as a model.
      Amlodipine concentration-dependently decreased the release of TNF-alpha and iNOS
      protein expression, and suppressed the degradation and phosphorylation of
      inhibitor of kappaB-alpha (IkappaB-alpha) in LPS-activated neonatal rat
      cardiomyocytes. Further studies revealed that amlodipine markedly activated
      phosphatidylinositiol 3-kinase (PI3K) and Akt, downstream of the PI3K signal
      cascade. Application of PI3K inhibitors, wortmannin and LY294002 attenuated the
      depression of TNF-alpha and iNOS expression by amlodipine in LPS-induced
      cardiomyocytes. These findings may explain some cardioprotective effects of
      amlodipine in LPS-mediated sepsis and suggest that the inhibition of TNF-alpha
      and iNOS expression by amlodipine is, at least in part, dependent on PI3K/Akt
      signaling pathway.

PMID- 19393776
TI  - Efficacy of laparoscopy in complicated appendicitis.
AB  - BACKGROUND: Laparoscopic appendectomy has been widely practiced for uncomplicated
      appendicitis. The role of laparoscopy in management of complicated appendicitis
      remains undefined. We undertook this study to evaluate the efficacy of
      laparoscopic appendectomy in patients with complicated appendicitis. METHOD: This
      study involved a total of 110 consecutive patients who had undergone appendectomy
      for perforated or gangrenous appendicitis between March 2004 and December 2008.
      Sixty-one patients underwent open appendectomy (OA) and remaining 49 patients
      underwent laparoscopic appendectomy (LA). Parameters studied were operative time,
      conversion rate, wound infections, intra-abdominal abscess and duration of pain
      and hospital stay. RESULTS: There were two conversions due to extremely friable
      appendix. Laparoscopic appendectomy took longer to perform (98 min versus 79 min)
      but was associated with less analgesic use, shorter median hospital stay (LA- 3
      days; OA- 6 days, p<0.05), and lower rate of wound infections (LA, 8.2%; OA, 24.6
      %, p<0.05). Intra-abdominal abscess occurred in four patients (8.2%) in LA group
      and fourteen patients (22.9%) in OA group (p<0.05). More patients in OA group
      experienced prolonged ileus than LA group but the difference was statistically
      insignificant. All complications were managed conservatively and there was no
      mortality in either group. CONCLUSIONS: Laparoscopic appendectomy for complicated
      appendicitis is feasible and safe. It is associated with less postoperative pain,
      lower incidence of infectious complications and reduced length of hospital stay
      when compared with patients who had open appendectomy.

PMID- 19393775
TI  - Accumulation of oxidative stress around the stroke-like lesions of MELAS
      patients.
AB  - To investigate the relationship between oxidative stress and progressive spread
      of the stroke-like lesions in mitochondrial myopathy, encephalopathy, lactic
      acidosis, and stroke-like episodes (MELAS) with 3243A>G mutation, we
      retrospectively analyzed the spread frequency in patients with and without
      treatment with the radical scavenger edaravone. Oxidative damage and defensive
      enzymes were histologically evaluated. Spread was significantly less frequent in
      the patients treated with edaravone. Although 8-hydroxy-2'-deoxyguanosine, a
      marker for oxidative damage of DNA, was obviously accumulated in peri-lesional
      surviving neurons, manganese superoxide dismutase and 8-oxoguanine glycosylase 1
      were not up-regulated in those neurons. Increased oxidative stress and
      insufficient defense could be involved in the pathogenesis of the spreading
      lesions in MELAS.

PMID- 19393777
TI  - The 'truth' about mammography screening? Nearing the end of a long and arduous
      Damascus Road.

PMID- 19393778
TI  - Evaluation of subfascial endoscopic perforator vein surgery (SEPS) using harmonic
      scalpel in varicose veins: an observational study.
AB  - INTRODUCTION: Conventional modalities used to treat varicose veins with
      incompetent perforators and subsequent stasis ulceration have proved to be
      effective, however there are associated morbidities, such as postoperative pain,
      limited mobility, wound infection and dehiscence. Recent advances have been made
      in minimally invasive vein surgery techniques to decrease operative morbidity,
      number and size of incisions, recovery time, and operative time. METHODS: A
      prospective study of 21 patients of varicose veins with incompetent perforators
      undergoing subfascial endoscopic perforator vein surgery (SEPS) using harmonic
      scalpel was designed and various parameters were studied. RESULTS: All ulcers
      healed in 8 weeks with no recurrence in 11.9 months follow-up period. One case of
      wound infection and each saphenous nerve neuropraxia were the only postoperative
      complications noted. CONCLUSION: Use of ultrasonic scalpel in SEPS is technically
      feasible, causes less tissue damage as it generates a low thermal effect, and is
      associated with minimal morbidity.

PMID- 19393780
TI  - Kernel density estimation and K-means clustering to profile road accident
      hotspots.
AB  - Identifying road accident hotspots is a key role in determining effective
      strategies for the reduction of high density areas of accidents. This paper
      presents (1) a methodology using Geographical Information Systems (GIS) and
      Kernel Density Estimation to study the spatial patterns of injury related road
      accidents in London, UK and (2) a clustering methodology using environmental data
      and results from the first section in order to create a classification of road
      accident hotspots. The use of this methodology will be illustrated using the
      London area in the UK. Road accident data collected by the Metropolitan Police
      from 1999 to 2003 was used. A kernel density estimation map was created and
      subsequently disaggregated by cell density to create a basic spatial unit of an
      accident hotspot. Appended environmental data was then added to the hotspot cells
      and using K-means clustering, an outcome of similar hotspots was deciphered. Five
      groups and 15 clusters were created based on collision and attribute data. These
      clusters are discussed and evaluated according to their robustness and potential
      uses in road safety campaigning.

PMID- 19393779
TI  - Proteomic analysis of enriched lysosomes at early phase of camptothecin-induced
      apoptosis in human U-937 cells.
AB  - A lysosomal pathway, characterized by partial rupture or labilization of
      lysosomal membranes and cathepsin activation, is evoked during camptothecin
      induced apoptosis in human cancer cells, including human histiocytic lymphoma U
      937 cells. These lysosomal events begin rapidly and simultaneously with
      mitochondrial permeabilization and caspase activation within 3 h after drug
      treatment. In this study, comparative and quantitative proteome analyses were
      performed to identify early changes in lysosomal protein expression/localization
      from U-937 cells undergoing apoptosis. In 2 independent experiments, among a
      total of more than 538 proteins putatively identified and quantitated by iTRAQ
      isobaric labeling and LC-ESI-MS/MS, 18 proteins were found to be upregulated and
      9 downregulated in lysosomes purified from early apoptotic compared to control
      cells. Protein expression was validated by Western blotting on enriched lysosome
      fractions, and protein localization confirmed by fluorescence confocal microscopy
      of representative protein candidates, whose functions are associated with
      lysosomal membrane fluidity and dynamics. These include sterol-4-alpha
      carboxylate 3-dehydrogenase (NSDHL), prosaposin (PSAP) and protein kinase C delta
      (PKC-delta). This comparative proteome analysis provides the basis for novel
      hypothesis and rationale functional experimentation, where the 3 validated
      candidate proteins are associated with lysosomal membrane fluidity and dynamics,
      particularly cholesterol, sphingolipid and glycosphingolipid metabolism.

PMID- 19393781
TI  - The effectiveness of audio-tactile lane-marking in reducing various types of
      crash: a review of evidence, template for evaluation, and preliminary findings
      from Australia.
AB  - Audio-tactile lane-marking (ATLM) is designed to alert inattentive drivers when
      they deviate from their lane. Most commonly used previously to mark the edges of
      divided freeways, it is increasingly used to mark the edge and/or centre of two
      lane undivided roads. We present a detailed review of ATLM evaluations to
      demonstrate that although both edge- and centreline ATLM appear to be effective,
      evaluations have been flawed insofar as they have (1) often not controlled
      adequately for variations due to extraneous factors known to affect crash
      incidence; (2) often focussed on total crashes, or on inattention-related
      crashes, and failed to address the possibility that ATLM increases some crash
      types (particularly crashes involving two-wheeled vehicles, out-of-control
      crashes, or crashes on the opposite side of the lane to which the ATLM is
      installed); (3) almost always related to the milled-in "rumble strips" employed
      in the US rather than the raised profile lane-marking (PLM) that is employed in
      Australia. The present Empirical Bayes analysis aimed to evaluate PLM by
      comparing treated and untreated sections of the same roads both before and after
      the date of treatment in terms a range of crash types (some separately for roads
      with only edgeline-PLM, with only centreline-PLM, and with both edgeline- and
      centreline-PLM). Although some of the above issues could not be addressed due to
      insufficient data, the analysis provides a useful template for future
      researchers. The results provide evidence that both edgeline and centreline
      (alone or in combination) reduce targeted (same-side) crashes. Although there is
      no evidence that edgeline and centreline alone increase opposite side crashes,
      only edgeline and centreline together produced a net reduction in total crashes.
      Thus, the present results suggest that installing PLM on both edgeline and
      centreline is preferable to installing either alone.

PMID- 19393782
TI  - Alcohol-impaired driving behavior and sensation-seeking disposition in a college
      population receiving routine care at campus health services centers.
AB  - Accidents stemming from alcohol-impaired driving are the leading cause of injury
      and death among college students. Research has implicated certain driver
      personality characteristics in the majority of these motor vehicle crashes.
      Sensation seeking in particular has been linked to risky driving, alcohol
      consumption, and driving while intoxicated. This study investigated the effect of
      sensation seeking on self-reported alcohol-impaired driving behavior in a college
      student population while adjusting for demographics, residence and drinking
      locations. A total of 1587 college students over the age of 18 completed a health
      screening survey while presenting for routine, non-urgent care at campus heath
      services centers. Student demographics, living situation, most common drinking
      location, heavy episodic drinking, sensation-seeking disposition and alcohol
      impaired driving behavior were assessed. Using a full-form logistic regression
      model to isolate sensation seeking after adjusting for covariates, sensation
      seeking remains a statistically significant independent predictor of alcohol
      impaired driving behavior (OR=1.52; CI=1.19-1.94; p<0.001). Older, white,
      sensation-seeking college students who engage in heavy episodic drinking, live
      off-campus, and go to bars are at highest risk for alcohol-impaired driving
      behaviors. Interventions should target sensation seekers and environmental
      factors that mediate the link between sensation seeking and alcohol-impaired
      driving behaviors.

PMID- 19393783
TI  - Costs and benefits to Sweden of Swedish road safety research.
AB  - This paper summarises a study designed to answer the following question: what are
      the benefits to Swedish society of road safety research in Sweden funded by the
      Swedish Transport Research Council and the programme for vehicle safety research
      during the period 1971-2004? The paper starts by discussing whether research can
      answer this question at all and explains why a well-controlled study was not
      feasible. A case study approach was selected, and five major research projects
      were examined in detail for the purpose of trying to estimate their effects on
      road safety. Estimates of safety effects were developed for four of the projects,
      indicating that road safety measures that were at least to some extent based on
      the findings of the research projects have made major contributions to reducing
      the number of road accident fatalities in Sweden. The estimates are not
      analytically rigorous and should be treated as qualified guesses only. Causal
      inferences are not possible. Nevertheless, if taken at face value, they show that
      the benefits to society of road safety research are large and outweigh by a wide
      margin the costs of the research, and of the road safety measures developed as a
      result of research. Thus, even if the estimated safety benefits exaggerate the
      true effects, the benefits of applied road safety research are likely to be
      greater than the costs of conducting this research and implementing road safety
      measures developed by research.

PMID- 19393784
TI  - Evaluation of the Scottsdale Loop 101 automated speed enforcement demonstration
      program.
AB  - Speeding is recognized as a major contributing factor in traffic crashes. In
      order to reduce speed-related crashes, the city of Scottsdale, Arizona
      implemented the first fixed-camera photo speed enforcement program (SEP) on a
      limited access freeway in the US. The 9-month demonstration program spanning from
      January 2006 to October 2006 was implemented on a 6.5 mile urban freeway segment
      of Arizona State Route 101 running through Scottsdale. This paper presents the
      results of a comprehensive analysis of the impact of the SEP on speeding
      behavior, crashes, and the economic impact of crashes. The impact on speeding
      behavior was estimated using generalized least square estimation, in which the
      observed speeds and the speeding frequencies during the program period were
      compared to those during other periods. The impact of the SEP on crashes was
      estimated using 3 evaluation methods: a before-and-after (BA) analysis using a
      comparison group, a BA analysis with traffic flow correction, and an empirical
      Bayes BA analysis with time-variant safety. The analysis results reveal that
      speeding detection frequencies (speeds> or =76 mph) increased by a factor of 10.5
      after the SEP was (temporarily) terminated. Average speeds in the enforcement
      zone were reduced by about 9 mph when the SEP was implemented, after accounting
      for the influence of traffic flow. All crash types were reduced except rear-end
      crashes, although the estimated magnitude of impact varies across estimation
      methods (and their corresponding assumptions). When considering Arizona-specific
      crash related injury costs, the SEP is estimated to yield about $17 million in
      annual safety benefits.

PMID- 19393785
TI  - Signal treatments to reduce heavy vehicle crash-risk at metropolitan highway
      intersections.
AB  - Heavy vehicle red-light running at intersections is a common safety problem that
      has severe consequences. This paper investigates alternative signal treatments
      that address this issue. A micro-simulation analysis approach was adopted as a
      precursor to a field trial. The simulation model emulated traffic conditions at a
      known problem intersection and provided a baseline measure to compare the effects
      of: an extension of amber time; an extension of green for heavy vehicles detected
      in the dilemma zone at the onset of amber; an extension of the all-red safety
      clearance time based on the detection of vehicles considered likely to run the
      red light at two detector locations during amber; an extension of the all-red
      safety-clearance time based on the detection of potential red-light runners
      during amber or red; and a combination of the second and fourth alternatives.
      Results suggested safety improvements for all treatments. An extension of amber
      provided the best safety effect but is known to be prone to behavioural
      adaptation effects and wastes traffic movement time unnecessarily. A green
      extension for heavy vehicles detected in the dilemma zone and an all-red
      extension for potential red-light runners were deemed to provide a sustainable
      safety improvement and operational efficiency.

PMID- 19393786
TI  - Evaluation of a roadside impairment test device using alcohol.
AB  - The main objective of this study was to compare the performance of a portable
      impairment test device known as roadside impairment testing apparatus (RITA) with
      the field impairment tests (FIT) that are used at the roadside by UK police. One
      hundred and twenty two healthy volunteers aged 18-70 years took part in this two
      period crossover evaluation. The volunteers received a dose of alcohol and
      placebo, in the form of a drink, on separate days. Doses were calculated to
      produce blood alcohol concentrations of 90 mg/100ml and RITA and FIT testing was
      carried out between 30 and 75 min post-drink. FIT was found to have a diagnostic
      accuracy of 62.7%. However, there was a substantial age effect for FIT scores,
      with volunteers aged over 40 showing failure rates on placebo similar to the
      failure rates on alcohol of younger volunteers. The accuracy of RITA was between
      66 and 70%, not significantly higher than that of FIT. However, RITA did not show
      a marked age effect. Advantageously, this could result in fewer false positives
      being recorded if RITA were deployed at the roadside. Horizontal gaze nystagmus
      (HGN) was also investigated and posted an accuracy of 74%. The inclusion of HGN
      as one component of a UK roadside impairment test battery warrants further
      exploration with other drugs.

PMID- 19393787
TI  - Short-term effects of a teenage driver cell phone restriction.
AB  - On December 1, 2006, North Carolina began prohibiting use of any mobile
      communication device by drivers younger than 18. The current study examined the
      effects of the law on teenage drivers' cell phone use. Teenage drivers were
      observed at high schools in North Carolina 1-2 months before and approximately 5
      months after the law took effect. The proportion of teenagers using cell phones
      did not change significantly (11.0% before the law took effect, 11.8% after).
      Cell phone use among teenage drivers at high schools in South Carolina, an
      adjacent state without a teenage driver phone ban, was stable at about 13%.
      Interviews were conducted with parents and teenagers in North Carolina both
      before and after the law took effect. In post-law interviews, teenagers were more
      likely than parents to say they knew about the cell phone restriction (64% vs.
      39%), but support for the ban was greater among parents (95% vs. 74%). Only 22%
      of teenagers and 13% of parents believed the law was being enforced fairly often
      or a lot. Although the proportion of teenagers who reported using phones while
      driving declined somewhat following the law, about half admitted they used their
      phones, if they had driven, on the day prior to the interview. Overall, the
      findings suggest that North Carolina's cell phone restriction had little to no
      effect on teenage drivers' use of cell phones shortly after the law took effect.

PMID- 19393788
TI  - Seat belt misuse among children transported in belt-positioning booster seats.
AB  - OBJECTIVE: Observe and report seat belt use among children transported in belt
      positioning booster seats. DESIGN: We conducted a cross-sectional, observational
      survey of children transported in motor vehicles between 2006 and 2007. While
      drivers completed a survey reporting the child's age, weight and gender, and the
      driver's age, gender, race, income, education, and relationship to the child; a
      child passenger safety technician recorded vehicle seating location, restraint
      type, and use of the car safety seat harness or seat belt as appropriate for the
      child. SETTING: Twenty-five fast food restaurants and discount department stores
      throughout Indiana. PARTICIPANTS: A convenience sample of drivers transporting
      children younger than 16 years. MAIN EXPOSURE: Seat belt use among children
      transported in belt-positioning booster seats. OUTCOME MEASURE: Seat belt misuse.
      RESULTS: Overall, 1446 drivers participated, 2287 children were observed with 564
      children in belt-positioning booster seats. At least one seat belt misuse was
      observed for 64.8% of the children transported. Common misuses were the shoulder
      belt being placed over the booster seat armrest (35.8%); shoulder belt not at mid
      shoulder position (28.5%), seat belt was too loose (24.5%), and the shoulder belt
      was either behind the child's back (9.1%) or under their arm (10.0%). CONCLUSION:
      There is a high frequency of seat belt misuses among children transported in
      booster seats. Advice to parents on appropriate car seat selection, and
      encouragement to parents to supervise seat belt use may decrease misuse.

PMID- 19393789
TI  - The value of a statistical life in Sweden: estimates from two studies using the
      "Certainty Approach" calibration.
AB  - Stated preference methods using surveys to elicit willingness to pay have been
      shown to suffer from hypothetical bias and scope/scale bias. Hypothetical bias
      usually means that willingness to pay is exaggerated in the hypothetical scenario
      and scope/scale bias means that there is an insensitivity in willingness to pay
      with regard to the amount of goods or the size of a good being valued.
      Experimental results in social psychology and economics have shown that only
      trusting the most certain respondents can potentially solve the problem with
      hypothetical bias and scope/scale bias. This paper presents the results of two
      different surveys in Sweden estimating the willingness to pay to reduce traffic
      mortality risks by only including the most certain respondents. Using the full
      sample, estimates of the value of a statistical life (VOSL) are $4.2 and $7.3
      million. Estimates of VOSL on the subset of the samples only including the most
      certain respondents are lower and consistent between the two surveys with values
      of $2.9 and $3.1 million.

PMID- 19393790
TI  - The effects of perception of risk and importance of answering and initiating a
      cellular phone call while driving.
AB  - Recent data suggest that laws banning cellular phone use while driving may not
      change use patterns, especially among young drivers with high rates of mobile
      phone adoption. We examined reasons younger drivers choose or do not choose to
      talk on a phone while driving among a sample of young drivers (n=276) with very
      high ownership of cellular phones (over 99%) and a very high use of cellular
      phones while driving (100% for those that were primary operators of an
      automobile). Respondents were surveyed for patterns of use, types of call,
      perceived risk, and motivations for use. The data were analyzed using structural
      equation modeling (SEM) to explore the relationships between perceived risk of
      the behavior, emotionality of the call, perceived importance of the call, and how
      often calls were initiated versus answered. The model suggests that even though
      people believe that talking on a cellular phone while driving is dangerous, they
      will tend to initiate a cellular conversation if they believe that the call is
      important.

PMID- 19393791
TI  - Video-based road commentary training improves hazard perception of young drivers
      in a dual task.
AB  - This study used a video-based hazard perception dual task to compare the hazard
      perception skills of young drivers with middle aged, more experienced drivers and
      to determine if these skills can be improved with video-based road commentary
      training. The primary task required the participants to detect and verbally
      identify immediate hazard on video-based traffic scenarios while concurrently
      performing a secondary tracking task, simulating the steering of real driving.
      The results showed that the young drivers perceived fewer immediate hazards
      (mean=75.2%, n=24, 19 females) than the more experienced drivers (mean=87.5%,
      n=8, all females), and had longer hazard perception times, but performed better
      in the secondary tracking task. After the road commentary training, the mean
      percentage of hazards detected and identified by the young drivers improved to
      the level of the experienced drivers and was significantly higher than that of an
      age and driving experience matched control group. The results will be discussed
      in the context of psychological theories of hazard perception and in relation to
      road commentary as an evidence-based training intervention that seems to improve
      many aspects of unsafe driving behaviour in young drivers.

PMID- 19393792
TI  - The impact of mental health symptoms on heavy goods vehicle drivers' performance.
AB  - High levels of psychological distress in fulltime employees are prevalent (4.5%
      per month). Symptoms of impaired mental health include difficulties with
      attention, concentration, motivation, decision-making, visuo-motor control, and
      psychomotor reaction times. There is limited research on the impact these
      symptoms have on heavy goods vehicle (HGV) drivers' performance. In this study
      1324 HGV drivers were surveyed using the Depression, Anxiety, Stress Scale (DASS)
      and the Health and Performance at Work Questionnaire (HPQ). Depression, anxiety
      and stress had little effect on driver absenteeism rates or self-rated driving
      performance. However, severe (1.5% of drivers) and very severe (1.8% of drivers)
      depression was associated with an increased odds ratio (OR=4.5 and 5.0,
      respectively) for being involved in an accident or near miss in the past 28 days.
      This odd ratio is akin to driving with a blood alcohol content of about 0.08%.
      Given the number of HGV vehicles and the prevalence of depression this equates to
      10,950 HGV drivers with an increased statistical risk of an accident or near
      miss. As the impact of HGV accidents is potentially large, including loss of
      life, it would be sensible to extend the research findings here into an action
      plan.

PMID- 19393793
TI  - Impairment related to blood drug concentrations of zopiclone and zolpidem
      compared to alcohol in apprehended drivers.
AB  - BACKGROUND: About 3-7% of the adult population receives prescribed hypnotics. The
      benzodiazepine-like hypnotics, zopiclone and zolpidem, are the most commonly
      prescribed and may cause traffic-relevant impairment similar to that found for
      benzodiazepines. We investigated the relationship between blood zopiclone and
      zolpidem concentrations and driving impairment, as assessed by the clinical test
      for impairment. We compared these groups of drivers to a group suspected of
      alcohol-related impairment. METHODS: Blood samples from suspected impaired
      drivers during 2000-2007, screened for approximately 25 possible impairing drugs
      with only one single drug detected, were studied in relation to the assessment of
      impairment. The 79 zopiclone positive drivers, the 43 zolpidem positive drivers,
      and the 3480 alcohol positive drivers were divided into groups depending on blood
      drug concentrations. RESULTS/DISCUSSION: The proportion of drivers judged as
      impaired tended to increase the higher the blood zopiclone concentrations. Such a
      positive relationship was not found for zolpidem. For alcohol the proportion of
      impaired drivers was significantly related to blood alcohol concentrations
      (BACs). There were few drivers with low zopiclone or zolpidem concentrations
      included, which may have obscured any positive significant relationship. The
      percentage of impaired drivers among drivers with blood zopiclone concentrations
      above 130 microg/l roughly corresponded to the percentage of impaired drivers
      among drivers with BACs higher than 0.1%.

PMID- 19393794
TI  - Factors affecting the severity of work related traffic crashes in drivers
      receiving a worker's compensation claim.
AB  - AIM: To examine factors that contribute to the severity of work related crashes
      in New South Wales, Australia. METHODS: Workers' Compensation data was linked to
      police crash records for the period 1998-2002. Multivariate analysis was carried
      out to assess the relationship between relevant risk factors and the severity of
      injury (permanent disability or death) in drivers who had received a claim for a
      work related crash. RESULTS: Age, gender, occupation, duty status, vehicle type,
      licence status, fatigue, speeding and location of the crash were independently
      associated with the severity of the crash. Drivers aged 65 years and older were
      nearly twice (OR: 1.824, 95% CI: 1.106-3.007) as likely to be permanently injured
      or die as a result of a work related crash compared to the younger age group (15
      24 years old). The risk to older drivers was even higher in crashes occurring
      while on duty. Drivers involved in traffic crashes while commuting were more
      likely to be severely injured (OR: 1.28, CI: 1.15-1.42) than those on duty.
      Compared to car drivers, taxi drivers were more than twice (OR: 2.38, CI: 1.726
      3.296) as likely to be severely injured. CONCLUSIONS: The findings contribute to
      bridging the gap in knowledge in the area of work related crashes and highlight
      the higher risk of permanent disability and death in older drivers, taxi drivers
      and commuters.

PMID- 19393795
TI  - Prevalence of psychoactive drug use among drivers in Thailand: a roadside survey.
AB  - The objective of this study was to determine the prevalence of psychoactive drug
      and alcohol use among general drivers and predictors of the drug use in Thailand.
      One thousand six hundred and thirty-five motor vehicle drivers were randomly
      selected from five geographical regions of Thailand between December 2005 and May
      2006. The prevalence of psychoactive drugs was determined using urine tests by
      gas chromatography/mass spectrometry (GC/MS). Among 1635 drivers, 5.5% were
      tested positive for breath alcohol with 2% having a level exceeding the legal
      limit (> or =50mg%). Psychoactive drug was presented in 158 (9.7%) urine samples
      for drug analysis. The top 3 most frequently detected licit drugs were
      antihistamines (2.0%), sedative cough suppressant (0.7%) and benzodiazepines
      (0.2%). Illicit drugs detected included amphetamine (1.8%), cannabis (1.1%),
      mitragynine (Kratom) (0.9%) and morphine (0.1%). Only type of driver
      (commercial/non-commercial) was a significant predictor with psychoactive drug
      use. The prevalence of psychoactive drug use among drivers not involved in road
      crashes in Thailand was not as low as an earlier study in Europe using objective
      measurements, particularly among commercial drivers. However, for illicit drugs,
      the prevalence detected in this study was lower than those of earlier studies
      from high-income countries.

PMID- 19393796
TI  - Modeling motorcycle helmet use in Iowa: evidence from six roadside observational
      surveys.
AB  - This paper investigates the influence of type of roadway, weather conditions and
      other factors on motorcycle helmet use rates in Iowa. Using data from six
      statewide roadside observational surveys of motorcycle helmet use, a bivariate
      probit model is estimated. The applied methodological approach allows for
      potentially interrelated choices of motorcycle helmet use by drivers and
      passengers to be examined. The estimation results can enhance our understanding
      of other factors than state helmet laws which correlate with motorcycle rider
      helmet use, and the effect that the presence of a passenger has on motorcycle
      driver helmet use rates.

PMID- 19393797
TI  - Illegal pedestrian crossing at signalised intersections: incidence and relative
      risk.
AB  - Illegal pedestrian behaviour is common and is reported as a factor in many
      pedestrian crashes. Since walking is being promoted for its health and
      environmental benefits, minimisation of its associated risks is of interest. The
      risk associated with illegal road crossing is unclear, and better information
      would assist in setting a rationale for enforcement and priorities for public
      education. An observation survey of pedestrian behaviour was conducted at
      signalised intersections in the Brisbane CBD (Queensland, Australia) on typical
      workdays, using behavioural categories that were identifiable in police crash
      reports. The survey confirmed high levels of crossing against the lights, or
      close enough to the lights that they should legally have been used. Measures of
      exposure for crossing legally, against the lights, and close to the lights were
      generated by weighting the observation data. Relative risk ratios were calculated
      for these categories using crash data from the observation sites and adjacent
      midblocks. Crossing against the lights and crossing close to the lights both
      exhibited a crash risk per crossing event approximately eight times that of legal
      crossing at signalised intersections. The implications of these results for
      enforcement and education are discussed, along with the limitations of the study.

PMID- 19393798
TI  - The effect of conformity tendency on pedestrians' road-crossing intentions in
      China: an application of the theory of planned behavior.
AB  - This paper presents a survey investigating the effects of age, gender and
      conformity tendency on Chinese pedestrians' intention to cross the road in
      potentially dangerous situations. A sample of 426 respondents completed a
      demographic questionnaire, a scale measuring their tendency towards social
      conformity, and a questionnaire based on the theory of planned behavior (TPB).
      This questionnaire measured people's intentions to cross the road in two
      different road crossing situations, their attitude towards the behavior,
      subjective norms, perceived behavioral control, anticipated affect, moral norms,
      and perceived risk. The two scenarios depicted (i) a situation where the crossing
      was consistent with other pedestrians' behavior (Conformity scenario) and (ii) a
      situation where the road crossing was inconsistent with other pedestrians (Non
      Conformity scenario). Pedestrians reported greater likelihood in crossing the
      road when other pedestrians were crossing the road. People who showed greater
      tendencies towards social conformity also had stronger road crossing intentions
      than low conformity people for both scenarios. The predictive model explained 36%
      and 48% of the variance in the Non-Conformity and Conformity scenarios,
      respectively. Attitude, subjective norm, perceived behavioral control, and
      perceived risk emerged as the common predictors for both situations. The results
      have a number of theoretical and practical implications. In particular,
      interventions should focus on perceptions of risk that inform road users that
      crossing with other pedestrians against the signal is also unsafe and prohibited,
      and may lead to negative outcomes.

PMID- 19393799
TI  - A longitudinal study of the effectiveness of a multi-media intervention on
      parents' knowledge and use of vehicle safety systems for children.
AB  - Motor-vehicle crashes are the leading cause of death and serious injury for
      children under the age of 14 in Canada and in the United States despite mandatory
      use of vehicle restraints since 1977. Using a pre- and post-test design, the
      present study tests the effectiveness of a multi-media intervention study on
      parents' knowledge of car safety seat use for children (0-12 years). The sample
      included 201 parents from four Ontario cities. Results indicate that parents'
      knowledge of when to accurately and safely transition a child to the appropriate
      car safety seat based on child's age, weight and height was retained at the 1
      year post-test for children 4-8 years of age. The rates of correct use of safety
      seats significantly increased 1 year following the intervention program. Other
      factors that influenced parent's knowledge included being a parent versus non
      parents, gender, income, education, sources of information, and regional
      location. The results of this study can help guide the development and
      implementation of future intervention programs and injury prevention policy.

PMID- 19393800
TI  - Seeing pedestrians at night: visual clutter does not mask biological motion.
AB  - Although placing reflective markers on pedestrians' major joints can make
      pedestrians more conspicuous to drivers at night, it has been suggested that this
      "biological motion" effect may be reduced when visual clutter is present. We
      tested whether extraneous points of light affected the ability of 12 younger and
      12 older drivers to see pedestrians as they drove on a closed road at night.
      Pedestrians wore black clothing alone or with retroreflective markings in four
      different configurations. One pedestrian walked in place and was surrounded by
      clutter on half of the trials. Another was always surrounded by visual clutter
      but either walked in place or stood still. Clothing configuration, pedestrian
      motion, and driver age influenced conspicuity but clutter did not. The results
      confirm that even in the presence of visual clutter pedestrians wearing
      biological motion configurations are recognized more often and at greater
      distances than when they wear a reflective vest.

PMID- 19393801
TI  - Discrepancy in bicycle helmet use among college students between two bicycle use
      purposes: commuting and recreation.
AB  - OBJECTIVES: The purpose of the study was to examine associations between bicycle
      helmet use and attitudes among U.S. college students. Bicycle helmet use was
      assessed for two different bicycle use purposes: commuting to school and
      recreation. MATERIALS AND METHODS: Student bicycle riders were recruited on the
      campus of a large public university in Colorado. Questionnaire development was
      guided by the Theory of Reasoned Action and Health Belief Model. Bicycle use and
      helmet use for the two purposes, attitudes toward helmet use and bicycle helmet
      regulations on campus, perceived risk of bicycle-related injury, subjective norms
      were asked. Bicycle helmet use was defined by current behaviors and intentions
      for the future, based on the Stages of Change model. RESULTS: A total of 192
      questionnaires collected from students who rode bicycles for both commuting and
      recreation was used for the analysis. Bicycle helmet use differed depending on
      purposes of bicycle riding: 9.4% of bicycle riders wore bicycle helmets every
      time for commuting, while 36.5% did so for recreation. Different variables were
      associated with bicycle helmet use for commuting and recreation in logistic
      regression models, suggesting that psychosocial structures behind bicycle helmet
      use behaviors might differ between two bicycle use purposes, commuting and
      recreation.

PMID- 19393802
TI  - Validity of surrogate measures of alcohol involvement when applied to nonfatal
      crashes.
AB  - Since the 1970s, nighttime fatal crashes have been used as a surrogate measure
      for alcohol-related fatalities for crashes for which more direct measures were
      absent. The validity of this approach was confirmed in 1985 but has not been re
      evaluated since. Although this measure has also been applied to identify alcohol
      involvement in nonfatal crashes, its validity when applied to nonfatal cases has
      never been determined. The objective of this study was to evaluate the
      appropriateness of using nighttime crashes as surrogate measures for alcohol
      impairment when applied to fatal and nonfatal injury and property damage only
      (PDO) crashes. To do so, we used data from a crash-control design study collected
      at the roadside in two U.S. states between 1997 and 1999, as well as from the
      1997-1999 and 2004-2006 Fatality Analysis Reporting System. The outcome of this
      study confirms the validity of using nighttime crashes as a surrogate measure for
      alcohol-related fatalities and supports the use of after-midnight crashes for
      measuring alcohol involvement in nonfatal and PDO crashes when the number of late
      night crashes permits.

PMID- 19393803
TI  - Effects of graduated driver licensing on licensure and traffic injury rates in
      Upstate New York.
AB  - OBJECTIVE: In 2003, New York State implemented an enhanced graduated driving
      licensing (GDL) program that requires extended supervised driving and a passenger
      restriction. This study examines its safety benefit in 55 Upstate New York
      counties. METHODS: We analyzed fatal/incapacitating traffic injury data among 16
      , 17- and 21-24-year olds for the years 2001 and 2005 using the negative binomial
      model. To adjust for trends in the traffic injury rate, the relative rate ratio
      (rRR) of 16- and 17-year olds relative to 21-24-year olds was estimated. RESULTS:
      GDL implementation was associated with a 31% reduction in the driver injury rate
      (rRR 0.69, 95% confidence interval (CI) 0.49-0.96), but not with any
      statistically significant change in the passenger injury rate (rRR 1.19, 95% CI
      0.77-1.84), or pedestrian and bicyclist injury rate (rRR 1.53, 95% CI 0.89-2.62)
      among 16-year olds. Sixteen-year olds experienced a 21% decline in licensure
      rates between 2001 and 2005. GDL implementation had no appreciable impact on
      driver injury and licensure rates for 17- and 21-24-year olds. CONCLUSIONS: GDL
      implementation is associated with a significant reduction in licensure and driver
      injury rate among 16-year olds. GDL implementation does not have a statistically
      significant impact on passenger, pedestrian, and bicyclist injury rates for 16
      year olds.

PMID- 19393804
TI  - Pedestrian fatality risk as a function of car impact speed.
AB  - Knowledge of the amount of violence tolerated by the human body is essential when
      developing and implementing pedestrian safety strategies. When estimating the
      potential benefits of new countermeasures, the pedestrian fatality risk as a
      function of impact speed is of particular importance. Although this function has
      been analysed previously, we state that a proper understanding does not exist.
      Based on the largest in-depth, pedestrian accident study undertaken to date, we
      derive an improved risk function for adult pedestrians hit by the front of
      passenger cars. Our results show far lower fatality risks than generally reported
      in the traffic safety literature. This discrepancy is primarily explained by
      sample bias towards severe injury accidents in earlier studies. Nevertheless, a
      strong dependence on impact speed is found, with the fatality risk at 50 km/h
      being more than twice as high as the risk at 40 km/h and more than five times
      higher than the risk at 30 km/h. Our findings should have important implications
      for the development of pedestrian accident countermeasures worldwide. In
      particular, the scope of future pedestrian safety policies and research should be
      broadened to include accidents with impact speeds exceeding 50 km/h.

PMID- 19393805
TI  - Evaluating the safety impacts of the number and arrangement of lanes on freeway
      exit ramps.
AB  - The primary objective of this study is to evaluate the impacts of the number and
      arrangement of lanes on freeway exit ramps on the safety performance of freeway
      diverge areas. The research team collected crash data at 343 freeway segments in
      the state of Florida. Four different types of exit ramps were considered in this
      study. They were defined as type 1, type 2, type 3, and type 4 exit ramps
      respectively. Cross-sectional comparison was conducted for comparing crash
      frequency, crash rate and crash severity between different types of freeway exit
      ramps. Crash prediction models were developed to identify the factors that
      contribute to the crashes reported at selected freeway segments and to provide
      quantified information regarding the safety impacts of different freeway exit
      ramps. It was found that the ramp and freeway AADT, posted speed limit on
      freeway, deceleration lane length, right shoulder width, and the type of exit
      ramp significantly affected the safety performance of freeway diverge areas. The
      study demonstrated the safety benefits of using lane-balanced exit ramps. Based
      on the crash prediction models, replacing a type 1 exit ramp (lane-balanced) with
      a type 2 exit ramp (not lane-balanced) will increase crash counts at freeway
      diverge areas by 68.33%. Replacing a type 3 ramp (lane-balanced) with a type 4
      ramp (not lane-balanced) will increase crash counts at freeway diverge areas by
      32.20%.

PMID- 19393806
TI  - Obstructive sleep apnoea among professional taxi drivers: a pilot study.
AB  - PURPOSE: This study aimed to describe the distribution of risk factors for
      obstructive sleep apnoea syndrome (OSAS) among taxi drivers, and to investigate
      differences by ethnicity in OSAS symptoms among drivers. METHODS: A two-page
      postal questionnaire was completed by 241 professional taxi drivers from
      Wellington, New Zealand. Obstructive sleep apnoea syndrome was defined as having
      an estimated 15 or more respiratory disturbances, per hour of sleep (Respiratory
      Disturbance Index (RDI)> or =15) and self-reported daytime sleepiness. RESULTS:
      Pacific and Maori taxi drivers were more likely to have symptoms and risk factors
      for OSAS, compared to non-Maori non-Pacific drivers. In particular, Pacific
      drivers had a significantly increased pre-test probability of having moderate
      severe OSA (RDI> or =15). CONCLUSIONS: Some professional taxi drivers are at
      increased risk for moderate-severe OSAS, especially Pacific and Maori taxi
      drivers. Untreated OSAS increases motor vehicle crash risk, so these findings
      have implications for the health and safety of drivers and their passengers. They
      suggest a need for more comprehensive research to guide policy on medical
      examinations required for licensing professional drivers as fit to drive.

PMID- 19393807
TI  - Heavy vehicle driver fatalities: learning's from fatal road crash investigations
      in Victoria.
AB  - This study describes the nature and extent of fatal heavy vehicle driver crashes
      in Victoria between 1999 and 2007 and the factors associated with the crash. A
      descriptive study was conducted comprising the population of heavy vehicle
      drivers killed in a road transport crash while operating a vehicle of > or =4.5
      tonne Gross Vehicle Mass (GVM) for the purposes of work. Information about the
      nature of crash, environmental, driver, vehicle and occupational factors were
      collected from the coroner's death investigation file. Of the 91 deaths
      identified 61 were eligible for review. All 61 cases were male, solo drivers with
      a mean age of 44.7 years. Most vehicles were articulated in configuration. One
      third of crash scenarios involved a single vehicle leaving the roadway on a
      straight road. One in every six fatally injured drivers was detected with the
      presence of stimulants or cannabis. Twenty-two drivers were travelling at
      excessive or inappropriate speeds for the circumstances. Seatbelt wearing status
      was documented for only 25 of 61 drivers. This study is the first to
      comprehensively examine a population of fatally injured heavy vehicle drivers
      using coroner's investigation files and these findings are consistent with
      previous, less detailed, Australian research. Information about potential
      associations between occupational factors and crash risk was limited. Improving
      driver safety requires incorporation of occupational factors into a standardised
      approach to heavy vehicle crash investigations.

PMID- 19393808
TI  - A mixed logit analysis of motorists' right-of-way violation in motorcycle
      accidents at priority T-junctions.
AB  - Research suggested that motorists' right-of-way (ROW) violation in automobile
      motorcycle gap-acceptance accidents at priority (i.e., stop-/yield-controlled) T
      intersections has been a safety concern to motorcyclists. This study examines the
      characteristics of automobile-motorcycle gap-acceptance accidents that occurred
      at such locations. British Stats19 accident injury database during 1991-2005 are
      examined in detail. Automobile-motorcycle gap-acceptance accidents are classified
      into three crash scenarios: approach-turn, angle crossing, and angle merging
      crashes. Mixed (random parameters) logit models are estimated to investigate the
      contributory factors to motorists' ROW violation in these three crash types.
      Crash features are also compared among gap-acceptance accidents and other crash
      scenarios. The methodological approach adopted allows for the individuals within
      the observations to have different parameter estimates as opposed to a single
      parameter representing all observations (i.e., accounts for unobserved
      heterogeneity potentially relating to roadway/environmental characteristics, and
      motorist behaviours). It was found that motorcycles' ROW was more likely to be
      violated on non-built-up roads, and in diminished light conditions, with non
      uniform effects across the observations. Elderly/female motorists appeared to be
      over-represented in gap-acceptance crashes. Implications of the findings are
      discussed.

PMID- 19393809
TI  - Validation of a Full Bayes methodology for observational before-after road safety
      studies and application to evaluation of rural signal conversions.
AB  - The objective of the study on which the paper is based was to explore the
      application of fully Bayesian methods for before-after road safety studies.
      Several variations of the methodology were evaluated with a simulated dataset in
      which hypothetical treatments with no safety effect were randomly assigned to
      high accident locations to mimic the common site selection process in road
      jurisdictions. It was confirmed that the fully Bayesian method by estimating no
      safety effect can account for the regression-to-the-mean that results from this
      biased site selection process. The fully Bayesian method was then applied to
      California rural intersection data to evaluate the safety effect of conversion
      from stop to signalized control. The results were then compared with those from
      the empirical Bayesian method, currently the accepted approach for conducting
      unbiased before-after evaluations. This comparison was generally favorable in
      that FB can provide similar results as EB.

PMID- 19393810
TI  - Alert eyes and DWIs: an indirect evaluation of a DWI witness reward program in
      Stockton, CA.
AB  - We evaluate a "grassroots" anonymous reward program targeting drunken driving in
      Stockton, CA. The time-series cross-sectional data covers 19 years for Stockton
      and six other California cities. Exploiting interrupted time-series regression,
      Zellner's seemingly unrelated regression (SUR) framework, and bootstrapped
      standard errors, we test for an impact of this program on alcohol-related injury
      or fatality accidents, the proportion of all accidents involving alcohol, and the
      number of DWI arrests. In its first decade, the citizen reward program appears to
      have averted some 275 alcohol-related accidents for social cost savings of
      between $21,000 and $5.6 million. Further, possibly 4495 arrests were precluded,
      saving some $1-3 million in arrest-related costs. Incentivized public monitoring
      of driving-after-drinking may be an effective drunken driving abatement program
      though our exploratory findings need further confirmation.

PMID- 19393811
TI  - Merging into heavy motorway traffic by young and elderly drivers.
AB  - An increase in the number of Heavy Goods Vehicles on motorways may lead to
      additional problems in the interaction with an increased number of elderly
      drivers. Elderly drivers suffer from reduced information processing speed and
      capacity, and in general effectively compensate for this by taking more time.
      However, this strategy, regulating task demands by slowing down will make merging
      into motorway traffic actually more difficult. In an experiment performed in a
      driving simulator, young and elderly drivers merged into motorway traffic. Driver
      behaviour and mental workload were studied while the following factors were
      manipulated: type of traffic and density of Heavy Goods Vehicles on the main
      road, the length of the acceleration lane, presence of a slowly driving lead car,
      and presence of a driver support system that encouraged the drivers to speed up
      if their speed was too low. Results show that the effects of an increased number
      of Heavy Goods Vehicles on the main road were not more adverse for elderly than
      for the young participants, with the exception that elderly drivers merged at a
      lower speed. This lower speed could make the manoeuvre more risky in real
      traffic. The support system and an extended acceleration lane facilitated
      merging, while a slowly driving lead car impeded completion of the manoeuvre.

PMID- 19393812
TI  - Evaluation of the static belt fit provided by belt-positioning booster seats.
AB  - Belt-positioning booster seats are recommended for children who use vehicle seat
      belts as primary restraints but who are too small to obtain good belt fit.
      Previous research has shown that belt-positioning boosters reduce injury risk,
      but the belt fit produced by the wide range of boosters in the US market has not
      previously been assessed. The present study describes the development of a method
      for quantifying static belt fit with a Hybrid-III 6-year-old test dummy. The
      measurement method was applied in a laboratory seat mockup to 31 boosters (10 in
      both backless and highback modes) across a range of belt geometries obtained from
      in-vehicle measurements. Belt fit varied widely across boosters. Backless
      boosters generally produced better lap belt fit than highback boosters, largely
      because adding the back component moved the dummy forward with respect to the lap
      belt routing guides. However, highback boosters produced more consistent shoulder
      belt fit because of the presence of belt routing guides near the shoulder. Some
      boosters performed well on both lap belt and shoulder belt fit. Lap belt fit in
      dedicated boosters was generally better than in combination restraints that also
      can be used with an integrated harness. Results demonstrate that certain booster
      design features produce better belt fit across a wide range of belt geometries.
      Lap belt guides that hold the belt down, rather than up, and shoulder belt guides
      integrated into the booster backrest provided better belt fit.

PMID- 19393813
TI  - Modeling drivers' speed selection as a trade-off behavior.
AB  - This paper proposes a new model of driver-preferred speeds derived from the
      assumption that drivers trade-off a portion of their safety for a time gain. The
      risk of receiving a ticket for speeding is also considered. A trip disutility
      concept is selected to combine the three components of speed choice (safety,
      time, and enforcement). The perceived crash risk and speed enforcement are
      considered as speed deterrents while the perceived value of a time gain is
      considered as a speed enticement. According to this concept, speeds that minimize
      the perceived trip disutility are preferred by drivers. The modeled trade-off
      behavior does not have to be fully rational since it is affected by drivers'
      preferences and their ability to perceive the risk. As such, the proposed
      framework follows the concept of bound rationality. The attractiveness of the
      model lies in its parameters being estimable with the observed preferred speeds
      and then interpretable as the factors of risk perception, the subjective value of
      time, and the perceived risk of speed enforcement. The proposed method may
      successfully supplement behavioral studies based on a driver survey. The study
      focuses on four-lane rural and suburban roads in Indiana, USA. The behavior of
      two types of drivers (trucks and cars) is modeled. The selection of test sites
      was such that the roads and other local characteristics varied across the studied
      sites while the population of drivers could be assumed as the same. The density
      of intersections, land development along the road, and the presence of sidewalks
      were the identified prominent risk perception factors. Another interesting
      finding is that the speed limit seems to encourage slow drivers to drive faster
      and fast drivers to drive slower.

PMID- 19393814
TI  - What can we learn about North Dakota's youngest drivers from their crashes?
AB  - For North Dakota teens, three of every four deaths are from motor vehicle
      crashes. Injury crash records for teen drivers were studied to gain insight
      regarding driver, vehicle, and road factors for public safety policy and program
      discussions. Results show 14-year-old drivers are three times more likely to die
      or be disabled in an injury crash than 17-year-old drivers, and that male drivers
      are 30% less likely to incur severe injury. As expected, seat belt use is a
      critical factor in severe injury avoidance. The likelihood for death or
      disablement is 165% greater for unbelted teen drivers than for those who are
      properly belted. In addition, rural and gravel roads pose a risk. Teens are six
      times more likely to be severely injured in crashes on rural roads than on urban
      roads. Findings suggest that an increased licensing age and seat belt emphasis
      may reduce teen traffic injuries in the state. In addition, more information on
      exposure should be attained to better understand rural and gravel road as risks.

PMID- 19393815
TI  - An analysis of common patterns in aggregated causation charts from intersection
      crashes.
AB  - Intersection crashes are a major traffic problem. Greater knowledge of causation
      is required in order to prevent them with the implementation of active safety
      measures. Causation charts were aggregated to establish whether common patterns
      of interlinked factors could be found. The data used comprised causation charts
      for 52 drivers involved in 26 in-depth investigated urban intersection crashes.
      The charts were compiled by means of the Driving Reliability and Error Analysis
      Method (DREAM) version 2.1, in which contributing factors are systematically
      analysed, classified and linked in a causation chart. The charts were aggregated
      for six defined risk situations, four for drivers without the right of way and
      two for those with the right of way. In two risk situations, one for drivers with
      and one for the drivers without the right of way, common patterns showed that the
      drivers had not seen the other vehicle due to distractions and/or sight
      obstructions. A frequently occurring pattern for the drivers with the right of
      way was that they had not expected another vehicle to cross their path. The
      absence of clear patterns in three risk situations for the drivers without the
      right of way was due to the low number of charts and rather unique circumstances.
      Parts of the aggregated charts showed an unwarranted variation, identified as a
      consequence of inconsistent charts. The present study shows that the rather
      unique approach of aggregating causation charts has potential, provided that the
      charts are consistent.

PMID- 19393816
TI  - Simplified method for evaluating energy loss in vehicle collisions.
AB  - A method is proposed for the evaluation of energy loss in road vehicle
      collisions. The energy loss evaluation is an essential task to reconstruct the
      dynamics of a road accident. The proposed method combines the simplicity of
      visual evaluation, typical of the method based on EES (equivalent energy speed),
      with flexibility, in order to evaluate the energy loss on any kind of vehicle
      deformation profile, of the methods based on measuring residual crush. The method
      is based on linearizing the damage profile, so that it is possible to
      predetermine the analytical expression of the kinetic energy loss in relation to
      only two parameters that characterise the shape of the damage. The stiffness of
      the vehicle is determined by estimating the geometric parameters of the damage
      starting from a photograph of generic damage, with documented EES, on a vehicle
      of the same model as the one under investigation. The proposed method was
      validated performing crash tests and using data from crash tests found in the
      literature. The method estimate with sufficient accuracy the kinetic energy loss
      in deformation on vehicles. The method, thanks to its simplicity and versatility,
      can constitute a valid alternative to the classic procedures for evaluating
      energy loss commonly utilised.

PMID- 19393817
TI  - Low stiffness floors can attenuate fall-related femoral impact forces by up to
      50% without substantially impairing balance in older women.
AB  - Low stiffness floors such as carpet appear to decrease hip fracture risk by
      providing a modest degree of force attenuation during falls without impairing
      balance. It is unknown whether other compliant floors can more effectively reduce
      impact loads without coincident increases in fall risk. We used a hip impact
      simulator to assess femoral neck force for four energy-absorbing floors
      (SmartCell, SofTile, Firm Foam, Soft Foam) compared to a rigid floor. We also
      assessed the influence of these floors on balance/mobility in 15 elderly women.
      We observed differences in the mean attenuation in peak femoral neck force
      provided by the SmartCell (24.5%), SofTile (47.2%), Firm Foam (76.6%), and Soft
      Foam (52.4%) floors. As impact velocity increased from 2 to 4m/s, force
      attenuation increased for SmartCell (from 17.3% to 33.7%) and SofTile (from 44.9%
      to 51.2%), but decreased for the Firm Foam (from 87.0% to 64.5%) and Soft Foam
      (from 66.1% to 37.9%) conditions. Regarding balance, there were no significant
      differences between the rigid, SmartCell, and SofTile floors in proportion of
      successful trials, Get Up and Go time, balance confidence or utility ratings.
      SofTile, Firm Foam, and Soft Foam caused significant increases (when compared to
      the rigid floor) in postural sway in the anterior-posterior and medial-lateral
      directions during standing. However, SmartCell increased sway only in the
      anterior-posterior direction. This study demonstrates that two commercially
      available compliant floors can attenuate femoral impact force by up to 50% while
      having only limited influence on balance in older women, and supports development
      of clinical trials to test their effectiveness in high-risk settings.

PMID- 19393819
TI  - Attentional control, high intensity pleasure, and risky pedestrian behavior in
      college students.
AB  - Individual differences in temperament and personality are closely linked to motor
      vehicle safety. However, 13% of Americans who die in transportation-related
      injuries are not killed in motor vehicle crashes, but rather in pedestrian
      injuries. This study was designed to study links between two individual
      difference measures, attentional control and high intensity pleasure, and
      pedestrian injury risk among college students, a group at particular risk of
      pedestrian injury. A sample of 245 students completed a temperament questionnaire
      and engaged in a street-crossing task within an interactive, immersive virtual
      pedestrian environment. Individuals scoring high on attentional control (the
      capacity to focus and shift attention, one facet of conscientiousness) waited
      longer to choose gaps to cross within and showed some tendency to choose larger
      gaps after waiting. Individuals scoring high in high intensity pleasure (the
      tendency to desire novel, complex, and varied stimuli, one facet of sensation
      seeking) were more likely to experience collisions with traffic in the virtual
      environment. Theoretical and applied implications are discussed.

PMID- 19393818
TI  - Alcohol, illicit and non-illicit psychoactive drug use and road traffic injury in
      Thailand: a case-control study.
AB  - The objective of this study was to determine the relationship between alcohol
      use, psychoactive drug use and road traffic injury (RTI). A case-control study
      was conducted among drivers in Bangkok, Thailand. Two hundred cases and 849
      controls were enrolled between February and November 2006. Cases who sustained a
      RTI were matched with four controls recruited from petrol stations within a 1-km
      radius of the reported crash site of the case. A positive alcohol breath test (>
      or =50mg/dl), and positive tests for the presence of illicit (amphetamine,
      cocaine, marijuana) and non-illicit psychoactive drugs (antihistamine,
      benzodiazepine, antidepressants), using gas chromatography/mass spectrometry
      (GC/MS) were documented as primary measures. There were significantly higher odds
      of an alcohol breath test > or =50mg/dl (adjusted odds ratio (OR) 63.6 (95% CI:
      25.5-158.9)), illicit psychoactive drugs (adjusted OR 3.4 (95% CI: 1.7-6.6)) and
      non-illicit psychoactive drug (adjusted OR 3.1 (95% CI: 1.5-6.3)) among cases
      than controls. Even though driving under the influence of psychoactive drugs has
      been significantly linked to RTI, its contribution to road safety is much lower
      than driving under the influence of alcohol. With limited resources, the priority
      for RTI prevention should be given to control of driving under the influence of
      alcohol.

PMID- 19393820
TI  - The potential role of nitric oxide in cardiovascular safety when treating
      osteoarthritis in patients with hypertension. Introduction.

PMID- 19393821
TI  - The impact of nitric oxide in cardiovascular medicine: untapped potential
      utility.
AB  - The structural integrity and functional activity of the endothelium play an
      important role in atherogenesis and related adverse outcomes. Cardiovascular
      disease risk conditions contribute to oxidative stress, which causes a disruption
      in the balance between nitric oxide (NO) and reactive oxygen species, with a
      resulting relative decrease in bioavailable NO and/or the NO-soluble guanylate
      cyclase cascade in blood vessels. This leads to endothelial and vascular smooth
      muscle cell dysfunction, resulting in increased tone and alterations in cell
      growth and gene expression that create a prothrombotic, proinflammatory
      environment. This leads to formation, progression, and destabilization of
      atherosclerotic plaques which may result in myocardial infarction, stroke, and
      cardiovascular death. NO clearly has a critical role in the maintenance and
      repair of the vasculature, and a decrease in bioavailable NO is linked to adverse
      outcomes. This background provides the rationale for exploring the potential
      therapeutic role for NO-donating agents in the prevention of adverse
      cardiovascular outcomes.

PMID- 19393822
TI  - Treatment of patients with hypertension and arthritis pain: new concepts.
AB  - Arthritis pain often occurs concurrently with hypertension and other
      cardiovascular risk factors. Treating patients with hypertension who have
      arthritis and other painful conditions can be a challenge because of potential
      risks associated with the agents commonly used to treat pain and inflammation.
      Hypertension is associated with endothelial dysfunction and decreased
      bioavailability of nitric oxide (NO). Naproxcinod, an investigational drug, is
      the first in a new class of agents called cyclooxygenase-inhibiting NO donators.
      They differ from traditional nonsteroidal anti-inflammatory drugs in their
      ability to donate NO, a signaling molecule known to have potentially beneficial
      effects on the vasculature and the gastrointestinal tract. Naproxcinod, by
      donating NO, offers a therapeutic option that might mitigate the negative blood
      pressure effects and adverse gastrointestinal effects associated with traditional
      arthritis therapies. This article reviews some preliminary preclinical and
      clinical studies of key safety data of an investigational new NO-donating anti
      inflammatory agent.

PMID- 19393823
TI  - The potential role of nitric oxide in cardiovascular safety when treating
      patients with osteoarthritis and hypertension: a moderated panel discussion.

PMID- 19393824
TI  - Defining the problem of treating the patient with hypertension and arthritis
      pain.
AB  - As osteoarthritis and hypertension coexist often in patients aged >60 years, the
      coadministration of nonsteroidal anti-inflammatory drugs (NSAIDs) with
      hypertension therapies is common practice in clinical medicine. Clinical trials
      in patients with arthritis have shown that many agents within the NSAID class may
      induce significant increases in systolic blood pressure, particularly when
      patients are using renin-angiotensin-blocking agents, beta-blockers, or diuretics
      as antihypertensives. The increases in blood pressure caused by NSAIDs are large
      enough to be of clinical concern. Sustained blood pressure elevations in the
      elderly are associated with increases in the risk of both ischemic and
      hemorrhagic stroke, congestive heart failure, and ischemic cardiac events.
      Recognition of the development of destabilization of blood pressure control in
      clinical practice and an awareness of those NSAIDs that place patients at risk
      for the development of hypertension could lead to reductions in cardiovascular
      morbidity.

PMID- 19393826
TI  - A novel deletion of BRCA1 gene that eliminates the ATG initiation codon without
      affecting the promoter region.
AB  - BACKGROUND: Point mutations in the highly penetrant cancer susceptibility gene
      BRCA1 are responsible for the majority of hereditary breast and/or ovarian
      cancer. We describe a novel large rearrangement of the BRCA1 gene identified in
      an Italian woman affected by an early onset bilateral breast cancer and a family
      history of hereditary breast cancer. The proband and her parents were negative
      for the presence of point mutations in BRCA1 and BRCA2 genes. METHODS: Multiplex
      ligation-dependent probe amplification (MLPA) was used to detect rearrangements
      in the BRCA1 gene. The breakpoint of the rearrangement identified in the proband
      was defined by restriction mapping and PCR amplification. BRCA1 mRNA encoded by
      the mutant allele was isolated from peripheral blood. RESULTS: The proband was
      heterozygous for a 9.1 kb deletion spanning from intron 1 to intron 3
      (g.1238_10350del) that eliminates exons 2 and 3 in the mature mRNA. In mutant
      mRNA exon 1a joins directly to exon 5 with no disruption of the reading frame.
      CONCLUSIONS: This deletion that eliminates the ATG initiation site in exon 2 and
      the sequence located in exons 2 and 3 encoding part of the RING finger domain of
      BRCA1 protein, is expected to abolish the function of this protein.

PMID- 19393828
TI  - Tomorrow's workforce for health: assessing the impact.

PMID- 19393829
TI  - Health Impact Assessment contributing to Healthy Public Policy.

PMID- 19393830
TI  - Introduction: targeting different pathways to prevent tumor cell development.

PMID- 19393831
TI  - Targeting tumor angiogenesis.
AB  - Our understanding of the process of tumor angiogenesis has changed significantly
      since the late 1970s, when vascular endothelial growth factor (VEGF) was first
      identified as vascular permeability factor and later found to be the major
      mediator of physiologic and pathologic angiogenesis. Since then, several
      additional VEGF-related ligands, VEGF receptors (VEGFRs), and
      complementary/alternative pathways that regulate tumor angiogenesis have been
      identified. Over the last decade, several antiangiogenic agents have been
      developed with the aim to inhibit new blood vessel growth, and we have learned
      that VEGF inhibition does far more than simply block new blood vessel growth.
      Clinical studies have demonstrated an improvement of progression-free and overall
      survivals with anti-VEGF therapy (with or without chemotherapy) in patients with
      advanced-stage malignancies. Unfortunately, even when anti-VEGF therapy is
      effective, the benefit of therapy is short-lived, with the development of tumor
      growth. We now recognize the presence of numerous complementary and redundant
      pathways that regulate tumor vasculature. For example, VEGF/VEGFR and
      angiopoietin/Tie-2 axes are two redundant, complementary components regulating
      tumor angiogenesis and vascular maintenance. The current clinical challenge is to
      identify: (1) factors that predict efficacy, and (2) markers of tumor response to
      anti-VEGF therapy, which can be achieved only by developing a thorough
      understanding of the biology of the VEGF system and the role of complementary
      pathways that may mediate resistance to anti-VEGF therapy.

PMID- 19393832
TI  - Proteasome inhibitors in multiple myeloma.
AB  - Discovery of the intracellular proteasome system for breakdown and removal of
      damaged or inappropriate proteins that might trigger apoptosis has led to the
      development of a whole new class of anticancer agents targeted to inhibit the
      proteasome and induce apoptosis. In vitro studies in multiple myeloma (MM)
      provide important insights into the use of proteasome inhibition to target both
      tumor cells and their microenvironment. Rapid development of the proteasome
      inhibitor bortezomib from biomolecular observations to clinical trials
      demonstrates how sophisticated appreciation of potential targets can expand the
      spectrum of novel agents available to treat difficult cancers, transforming
      disease management in these patients. In addition, high-throughput advanced
      protein and gene studies are key to develop preclinical assessments of
      potentially useful combination therapy and to guide clinical trials to improve
      efficacy using multiple agents.

PMID- 19393833
TI  - Anaplastic lymphoma kinase (ALK)-induced malignancies: novel mechanisms of cell
      transformation and potential therapeutic approaches.
AB  - Among the many oncogenic variants of the anaplastic lymphoma kinase (ALK),
      nucleophosmin 1 (NPM)/ALK fusion protein expressed in the subset of T-cell
      lymphoma (ALK(+)TCL) is currently the best characterized. NPM/ALK activates
      several signal transduction pathways, including PI3K/AKT, MEK/ERK, mTORC1, STAT3,
      and STAT5b. In turn, the pathways modulate expression and function of many genes
      and proteins involved in the key cellular functions such as proliferation,
      growth, survival, metabolism, and angiogenesis. Recent data indicate that NPM/ALK
      also promotes immune evasion of the ALK(+)TCL by inducing through STAT3
      activation the expression of immunosuppressive cytokines interleukin-10 (IL-10)
      and transforming growth factor-beta (TGFss) and cell surface protein CD274 (PD
      L1, B7-H1). In addition, NPM/ALK protects its own expression by mediating via
      STAT3 and at least one member of the DNA methyltransferase family DNMT1
      epigenetic silencing of the SHP-1 and STAT5a genes. In ALK+TCL cells, SHP-1 and
      STAT5a proteins act as potent tumor suppressors by promoting degradation of the
      NPM/ALK protein and inhibiting expression of the NPM/ALK gene, respectively.
      These findings provide further rationale to therapeutically target ALK and its
      effector proteins, foremost STAT3. They also suggest that immunotherapeutic
      approaches to ALK(+)TCL and, possibly, other ALK-driven malignancies may require
      inhibition of ALK and STAT3 to achieve the optimal clinical efficacy.

PMID- 19393834
TI  - Cell culture modeling of genotype-directed sensitivity to selective kinase
      inhibitors: targeting the anaplastic lymphoma kinase (ALK).
AB  - Selective kinase inhibitors have emerged as an important class of cancer
      therapeutics. The clinical success of drugs such as imatinib, erlotinib, and
      lapatinib, together with findings demonstrating the important relationship
      between specific tumor genotypes and clinical response to these agents, also has
      brought to the forefront the concept of "personalized cancer medicine." The
      potential broader significance of this relationship has been further highlighted
      in preclinical studies using tumor-derived cell lines as a model system that can
      faithfully recapitulate the association of specific genotypes with drug
      sensitivity, suggesting the utility of cancer cell lines to identify novel
      candidate biomarkers for predicting clinically responsive patient subsets for
      newly developed anticancer agents. The case of the anaplastic lymphoma kinase
      (ALK) nicely exemplifies this, and cell line profiling has revealed that ALK
      mutations present in a subset of anaplastic large cell lymphomas (ALCLs), non
      small cell lung cancers (NSCLCs), and neuroblastomas appear to sensitize cancer
      cells to treatment with selective ALK kinase inhibitors. Such findings suggest
      that genotype-based stratification of cancer patients for treatment with
      selective kinase inhibitors, even across multiple diseases of distinct tissue
      origin, may be essential for maximizing their clinical benefit.

PMID- 19393835
TI  - Understanding DNA damage response and DNA repair pathways: applications to more
      targeted cancer therapeutics.
AB  - Radiation therapy and many of the commonly used cancer chemotherapeutic drugs
      target DNA for cytotoxicity. Indeed, the subsequent DNA damage response (DDR) to
      these cancer treatments in both malignant and normal cells/tissues determines the
      therapeutic index (TI) of the treatment. The DDR is a complex set of cell
      processes involving multiple DNA repair, cell cycle regulation, and cell
      death/survival pathways (or networks) with both damage specificity and
      coordination of the DDR to different types of DNA damage. Over the last decade,
      significant progress has been made in elucidating these complex cellular and
      molecular networks involved in the DDR in human tumor and normal tissues. Based
      on what has been learned about these processes using experimental in vitro and in
      vivo models, DDR and DNA pathways are now potential targets for cancer therapy.
      This article presents an overview of our current understanding of the DDR,
      including the key DNA repair pathways involved in determining the cytotoxicity to
      several classes of chemotherapy drugs (CT) as well as ionizing radiation (IR).
      Since many different types of human cancers can arise from genetic or epigenetic
      changes in the DDR and DNA repair pathways, this article also covers recent
      developments in cancer therapeutics that attempt to target these specific tumor
      related DDR/DNA repair defects as monotherapy or, more commonly, when combined
      with conventional cancer treatments.

PMID- 19393837
TI  - Janus kinase mutations.
AB  - The chronic myeloproliferative neoplasms (MPNs) polycythemia vera (PV), essential
      thrombocytosis (ET), and primary myelofibrosis (MF) are commonly associated with
      mutations in the Janus kinase gene JAK2. A hallmark of PV is an abundance of red
      blood cells; ET, too many platelets; and MF, accumulation of neutrophils and
      monocytes accompanied by bone marrow fibrosis and bone marrow failure. Although
      knowledge of PV, ET, and MF has expanded considerably in the last decade, the
      pathophysiology behind these disorders is complex, and some of the underlying
      mechanisms are still unknown. The knowledge gap for these diseases has been
      compounded by the observation that a subset of patients with PV, ET, and MF do
      not present with mutations that activate JAK2. Recent studies suggest JAK
      inhibitors may offer significant benefit to patients with these MPNs and may have
      a role in the treatment of other malignancies that are also driven, at least in
      part, by activation of JAK signaling. However, additional genetic and functional
      studies are needed to identify the patients that will benefit most from JAK
      kinase inhibitors.

PMID- 19393836
TI  - Role of c-Met in cancer: emphasis on lung cancer.
AB  - Lung cancer remains the leading cause of cancer death. It is often diagnosed at
      late stages and is treated systemically with cytotoxic chemotherapy, which is
      generally ineffective. Research efforts have focused on developing therapies
      targeted to growth factor receptor pathways, such as epidermal growth factor
      receptor (EGFR), but the results from clinical trials overall show very small
      improvements in survival. Research on signaling pathways dysregulated in lung
      cancer is ongoing, including investigation of the hepatocyte growth factor
      receptor (HGFR) or c-Met. Protein tyrosine kinases, such as EGFR and c-Met, are a
      family of oncogenes that regulate important cellular processes, such as
      differentiation, proliferation, cell cycle, motility, and apoptosis. Hepatocyte
      growth factor (HGF), a ligand for c-Met, is secreted by mesodermal cells during
      development. It produces multiple effects upon binding to its receptor (HGFR/c
      Met) and regulates proliferation, motility, mitogenesis, and morphogenesis.
      Studies in cell lines isolated from various tumors show that several
      intracellular pathways participate in c-Met signaling, including growth factor
      receptor-bound protein 2 (Grb2), mitogen-activated protein (MAP) kinase,
      phosphoinositol 3-kinase (PI3K), and phospholipase C-gamma (PLC-gamma). c-Met is
      overexpressed in many tumors. However, overexpression may not be sufficient to
      cause increased activity; the receptor needs to be activated. In some cases, the
      kinases are constitutively active due to mutations in the gene. The cytoskeletal
      protein paxillin also appears to be activated along with c-Met. Correlative
      studies from patient tissue samples and cell lines have rendered the same
      information, indicating that the signaling pathways dysregulated are complex and
      interdependent. Mutations in human c-Met have been exogenously expressed in
      Caenorhabditis elegans, which can serve as a model for determining the role of
      gene mutations in a whole organism. Several inhibitors of c-Met/HGF binding are
      in development, including some in phase I trials. Their effectiveness in
      improving cancer outcomes will be determined in the near future.

PMID- 19393838
TI  - Nebivolol: a third-generation beta-blocker for hypertension.
AB  - BACKGROUND: Nebivolol is a third-generation beta(1)-selective beta-blocker that
      is approved for the treatment of hypertension. OBJECTIVE: This article reviews
      the clinical pharmacology of nebivolol and its efficacy and safety profile in
      clinical studies of hypertension (the US Food and Drug Administration-approved
      indication) and heart failure (off-label use). METHODS: Pertinent articles were
      identified through searches of MEDLINE and Current Contents from 1966 through
      December 15, 2008, using the terms nebivolol, drug interaction, pharmacokinetics,
      and pharmacology. The reference lists of the identified publications were
      reviewed for additional references. Abstracts presented at meetings of the
      American Heart Association and the American Society of Hypertension from 2006
      through 2008 were also reviewed. All human clinical trials were included,
      regardless of design. RESULTS: Twelve published clinical trials were identified
      that evaluated the use of nebivolol in the management of hypertension; 1 was
      placebo controlled, 1 was placebo and active controlled, and 10 involved direct
      comparisons with other antihypertensive agents. Nebivolol was reported to be as
      effective in lowering blood pressure (BP) as other beta-blockers (atenolol and
      bisoprolol), angiotensin-converting enzyme inhibitors (lisinopril and enalapril),
      the angiotensin-receptor blocker telmisartan, and calcium channel blockers
      (nifedipine and amlodipine). No published studies were identified that evaluated
      the effect of nebivolol on long-term cardiovascular outcomes. In data from a
      study in heart failure, nebivolol was associated with a 14% reduction in all
      cause mortality and cardiovascular hospitalization at 12 months (P < 0.05). In
      comparative clinical studies, nebivolol appeared to be well tolerated relative to
      the other antihypertensive agents studied. The most commonly reported adverse
      events with nebivolol were fatigue (4%-79%), headache (2%-24%), paresthesia (7%
      13%), bradycardia (6%-11%), rhinitis (1%-7%), and dizziness (2%-5%). Because of
      differences in its pharmacologic properties, nebivolol may have potential
      advantages in patients who are unable to tolerate traditional beta-blockers (eg,
      patients with asthma or chronic obstructive pulmonary disease, or men who
      experience erectile dysfunction while taking antihypertensive therapy).
      CONCLUSIONS: Nebivolol is a cardioselective beta-blocker that has been reported
      to be efficacious and well tolerated for achieving BP control in patients with
      hypertension. Preliminary evidence suggests a potential for reduced mortality in
      patients with heart failure.

PMID- 19393839
TI  - Varenicline: a first-line treatment option for smoking cessation.
AB  - BACKGROUND: Varenicline acts as a partial agonist/antagonist with affinity and
      selectivity for alpha(4) beta(2) nicotinic acetylcholine receptors. This activity
      at the nicotine-receptor level may help patients achieve smoking cessation by
      reducing cravings/withdrawal symptoms and smoking satisfaction. OBJECTIVE: This
      article reviews the literature on the pharmacologic properties, therapeutic
      efficacy, and tolerability of varenicline for smoking cessation. METHODS:
      Pertinent controlled clinical trials, meta-analyses, meeting abstracts, case
      reports, and review articles published in English between 1966 and May 2008 were
      identified through searches of MEDLINE and OVID using the terms varenicline,
      smoking, tobacco cessation, and CP 526555. RESULTS: Eight clinical trials were
      identified that compared <or=12 weeks of varenicline treatment with placebo
      and/or bupropion sustained release (SR); one of the trials reported follow-up
      data to 24 weeks, and the remainder reported data to 52 weeks. During treatment
      with oral varenicline titrated to 1 mg BID, CO-confirmed 4-week continuous quit
      rates/continuous abstinence rates (CQRs/CARs) in weeks 9 through 12 ranged from
      43.9% (odds ratio [OR] = 3.85 [95% CI, 2.69-5.50; P < 0.001 vs placebo]; OR =
      1.90 [95% CI, 1.38-2.62; P < 0.001 vs bupropion SR]) to 65.4% (OR = 2.98 [95% CI,
      1.78-4.99; P < 0.001 vs placebo]). In 4 of these trials, varenicline 1 mg BID was
      associated with significantly higher CQRs/CARs compared with placebo at week-52
      follow-up, ranging from 21.9% (P < 0.001) to 34.6% (P = 0.036). One trial
      reported a significantly higher CAR at 52 weeks with varenicline compared with
      bupropion SR (23.0% vs 14.6%, respectively; P = 0.004), and another reported a
      significantly higher CAR at 52 weeks with varenicline compared with nicotine
      replacement therapy (25.9% vs 19.8%, respectively; P = 0.040). In a relapse
      prevention study that included a 12-week extension period for participants who
      were abstinent after the initial 12 weeks of treatment, CARs were significantly
      improved at 24 weeks with varenicline relative to placebo (70.5% vs 49.6%,
      respectively; OR = 2.48; 95% CI, 1.95-3.16; P < 0.001). Treatment with
      varenicline was generally well tolerated in study populations with no major
      comorbidities. In a pooled analysis of 2 Phase III trials, the most commonly
      reported adverse events (AEs) with varenicline, bupropion SR, and placebo were
      nausea (28.8%, 9.9%, and 9.1%, respectively), insomnia (14.2%, 21.5%, and 12.6%),
      and headache (14.2%, 11.1%, and 12.4%). In a pooled analysis of 2 identically
      designed Phase III trials, bupropion SR was associated with the highest overall
      rates of discontinuation due to all-cause AEs compared with varenicline and
      placebo (13.9%, 9.5%, and 8.2%, respectively) and due to AEs considered related
      to study drug (12.1%, 7.9%, and 6.4%). In double-blind clinical trials of
      varenicline, nausea was the most frequently reported AE (16.3%-41.9%).
      Varenicline treatment should begin 7 days before the proposed smoking quit date;
      dose titration is recommended to minimize dose-related nausea. Based on
      postmarketing reports of serious AEs in vareniclinetreated patients, caution is
      recommended when operating vehicles or heavy machinery. Patient education and
      monitoring for potential AEs are also recommended, particularly in patients with
      a history of psychiatric illness. CONCLUSIONS: Varenicline has a unique mechanism
      of action compared with other first-line options for smoking cessation. Available
      clinical-trial data support its use as an effective and generally well-tolerated
      therapy for smoking cessation in healthy adult smokers, although there is a need
      for further efficacy and safety evaluation in the general population,
      particularly those with comorbid conditions.

PMID- 19393840
TI  - Self-reported sedation profile of immediate-release quetiapine fumarate compared
      with extended-release quetiapine fumarate during dose initiation: a randomized,
      double-blind, crossover study in healthy adult subjects.
AB  - OBJECTIVES: The primary study objective was to assess the time course and
      intensity of sedation after administration of immediate-release (IR) and extended
      release (XR) quetiapine fumarate in healthy subjects during dose initiation. The
      tolerability of the 2 formulations was also evaluated. METHODS: This was a
      randomized, double-blind, double-dummy, 2-period crossover study in healthy adult
      (age 18-50 years) subjects. It employed the dose-initiation schedule used in
      studies of the 2 quetiapine formulations in patients with bipolar depression: 50
      mg on day 1, 100 mg on day 2, 200 mg on day 3, and 300 mg on days 4 and 5. Doses
      were administered in the morning. The primary end point was the level of sedation
      1 hour after dosing on day 1, as rated by subjects using a visual analog scale
      (VAS) ranging from 0 = alert to 100 = drowsy. Secondary VAS end points included
      sedation over a 14-hour period on day 1, and on days 2 through 5. Blood was drawn
      on day 5 of both periods for determination of plasma drug concentrations by a
      liquid chromatography method with tandem mass-spectrometric detection. Adverse
      events (AEs) were recorded throughout the study. RESULTS: Sixty-three subjects
      were enrolled in the study, comprising the safety population. The perprotocol
      population consisted of 58 subjects (79.0% male, 21.0% female; 67.2% black, 24.1%
      white; mean age, 31.8 years; mean weight, 80.7 kg). One hour after dosing on day
      1, sedation was significantly greater with quetiapine IR than with quetiapine XR
      (mean VAS score, 33.2 vs 11.3, respectively; P < 0.001). There were no
      significant differences in sedation between formulations at 7 hours after dosing
      (64.5 and 53.6), 8 hours after dosing (46.9 and 50.8), or 14 hours after dosing
      (both, 12.7). On day 1, numerically more subjects had a VAS score>75 (substantial
      sedation) 1 hour after dosing in the quetiapine IR group than in the quetiapine
      XR group (14 vs 4 subjects). On day 5, the mean (95% CI) quetiapine C(max) for
      the IR and XR formulations was 689.19 (605.83-784.02) and 381.70 (341.40-426.76)
      ng/mL; the mean was AUC(0-11) was 2835.89 (2517.92-3194.02) and 2515.21 (2281.76-
      2772.55) ng . h/mL; and the median T(max) was 2.0 and 5.0 hours. The incidence of
      any AEs was 21.7% with quetiapine IR and 9.8% with quetiapine XR. CONCLUSION: In
      these healthy subjects, quetiapine XR was associated with a lower intensity of
      self-reported sedation compared with quetiapine IR. ClinicalTrials.gov
      Identifier: NCT00702676; Astra Zenecaclinicaltrials.com Identifier: D1443C00033.

PMID- 19393841
TI  - Efficacy and safety of low-dose transdermal buprenorphine patches (5, 10, and 20
      microg/h) versus prolonged-release tramadol tablets (75, 100, 150, and 200 mg) in
      patients with chronic osteoarthritis pain: a 12-week, randomized, open-label,
      controlled, parallel-group noninferiority study.
AB  - OBJECTIVE: This study compared the efficacy and safety of low-dose 7-day
      buprenorphine patches and prolonged-release tramadol tablets in patients with
      chronic, moderate to severe osteoarthritis (OA) pain of the hip and/or knee.
      METHODS: Eligible patients were adults with a clinical and radiologic diagnosis
      of OA of the hip and/or knee and moderate to severe pain, as confirmed by a mean
      Box Scale 11 (BS-11) score >or=4 while using paracetamol 4000 mg/d for pain
      during the screening week. Patients were randomized in a 1:1 ratio to receive
      either low-dose 7-day buprenorphine patches (patch strengths of 5, 10, and 20
      microg/h, with a maximum dosage of 20 microg/h) or twice-daily prolonged-release
      tramadol tablets (tablet strengths of 75, 100, 150, and 200 mg, with a maximum
      dosage of 400 mg/d) over a 12-week open-label treatment period. Supplementary
      paracetamol was available as rescue medication throughout the study. The primary
      end point was the difference in BS-11 scores from baseline to the completion of
      treatment. Noninferiority was assumed if the treatment difference on the BS-11
      scale was -1.5 boxes, indicating a clinically meaningful result. Secondary
      efficacy variables were rescue medication use, sleep disturbance and quality of
      sleep, and patients' and investigators' global assessments of pain relief. In
      addition, patient preference was assessed at the completion visit by asking
      patients whether, given equal pain relief, they would prefer basic treatment for
      OA pain with a patch applied once weekly or a tablet taken twice daily.
      Exploratory variables included investigators' assessments of patients' pain,
      stiffness, and ability to perform daily activities (Western Ontario and McMaster
      Universities Osteoarthritis Index); patients' quality of life (EuroQol EQ-5D
      health states index and EuroQol visual analog scale); and abuse and diversion of
      study drug. RESULTS: One hundred thirty-four patients (69 receiving 7-day
      buprenorphine patches and 65 receiving tramadol tablets) were randomized and
      received >or=1 dose of study medication. A respective 98.6% and 100% of the 2
      treatment groups were white, with mean (SD) ages of 64.4 (11.1) and 64.2 (9.3)
      years. Both treatments were associated with a clinically meaningful reduction in
      pain from baseline to study completion. The least squares mean change from
      baseline in BS-11 scores in the 7-day buprenorphine patch and tramadol tablet
      groups was -2.26 (95% CI, -2.76 to -1.76) and -2.09 (95% CI, -2.61 to -1.58). The
      efficacy of 7-day buprenorphine patches was noninferior to that of prolonged
      release tramadol tablets. The incidence of adverse events (AEs) was comparable in
      the 2 treatment groups: 226 AEs were reported in 61 patients (88.4%) in the 7-day
      buprenorphine patch group, and 152 AEs were reported in 51 patients (78.5%) in
      the tramadol group. Ten patients (14.5%) in the 7-day buprenorphine patch group
      and 19 (29.2%) in the tramadol tablet group withdrew from the study due to AEs.
      The most common AEs in the 7-day buprenorphine patch group were nausea (30.4%),
      constipation (18.8%), and dizziness (15.9%); the most common AEs in the tramadol
      tablet group were nausea (24.6%), fatigue (18.5%), and pain (12.3%). Most
      patients (47/67 [70.1%] in the 7-day buprenorphine patch group and 43/61 [70.5%]
      in the tramadol tablet group) reported that they would prefer a 7-day patch to a
      twice-daily tablet for future pain treatment. CONCLUSIONS: In these patients with
      chronic, moderate to severe OA pain of the hip and/or knee, 7-day low-dose
      buprenorphine patches were an effective and well-tolerated analgesic. The
      buprenorphine patches were noninferior to prolonged-release tramadol tablets.
      European Union Drug Regulating Authorities Clinical Trials number: 2006-003233
      32.

PMID- 19393842
TI  - Besifloxacin ophthalmic suspension 0.6% in patients with bacterial
      conjunctivitis: A multicenter, prospective, randomized, double-masked, vehicle
      controlled, 5-day efficacy and safety study.
AB  - BACKGROUND: Besifloxacin ophthalmic suspension 0.6% is a new topical
      fluoroquinolone for the treatment of bacterial conjunctivitis. Besifloxacin has
      potent in vitro activity against a broad spectrum of ocular pathogens, including
      drug-resistant strains. OBJECTIVE: The primary objective of this study was to
      compare the clinical and microbiologic efficacy of besifloxacin ophthalmic
      suspension 0.6% with that of vehicle (the formulation without besifloxacin) in
      the treatment of bacterial conjunctivitis. METHODS: This was a multicenter,
      prospective, randomized, double-masked, vehicle-controlled, parallel-group study
      in patients with acute bacterial conjunctivitis. Patients received either topical
      besifloxacin ophthalmic suspension or vehicle administered 3 times daily for 5
      days. At study entry and on days 4 and 8 (visits 2 and 3), a clinical assessment
      of ocular signs and symptoms was performed in both eyes, as well as pinhole
      visual acuity testing, biomicroscopy, and culture of the infected eye(s). An
      ophthalmoscopic examination was performed at study entry and on day 8. The
      primary efficacy outcome measures were clinical resolution and eradication of the
      baseline bacterial infection on day 8 in culture-confirmed patients. The safety
      evaluation included adverse events, changes in visual acuity, and biomicroscopy
      and ophthalmoscopy findings in all patients who received at least 1 dose of
      active treatment or vehicle. RESULTS: The safety population consisted of 269
      patients (mean [SD] age, 34.2 [22.3] years; 60.2% female; 82.5% white) with acute
      bacterial conjunctivitis. The culture-confirmed intent-to-treat population
      consisted of 118 patients (60 besifloxacin ophthalmic suspension, 58 vehicle).
      Significantly more patients receiving besifloxacin ophthalmic suspension than
      vehicle had clinical resolution of the baseline infection at visit 3 (44/60
      [73.3%] vs 25/58 [43.1%], respectively; P < 0.001). Rates of bacterial
      eradication also were significantly greater with besifloxacin ophthalmic
      suspension compared with vehicle at visit 3 (53/60 [88.3%] vs35/58 [60.3%]; P <
      0.001). The cumulative frequency of adverse events did not differ significantly
      between the 2 groups (69/137 [50.4%] and 70/132 [53.0%]). The most common ocular
      adverse events were eye pain (20/190 treated eyes [10.5%] and 13/188 [6.9%]),
      blurred vision (20/190 [10.5%] and 22/188 [11.7%]), and eye irritation (14/190
      [7.4%] and 23/188 [12.2%]); these events were of mild or moderate severity.
      Changes in visual acuity and treatment-emergent events observed on biomicroscopy
      and direct ophthalmoscopy also were comparable between treatment groups.
      CONCLUSION: Besifloxacin ophthalmic suspension 0.6% given 3 times daily for 5
      days was both efficacious and well tolerated compared with vehicle in the
      treatment of these patients with bacterial conjunctivitis. ClinicalTrials.gov
      Identifier: NCT00622908.

PMID- 19393843
TI  - Effects of intravenous patient-controlled analgesia with buprenorphine and
      morphine alone and in combination during the first 12 postoperative hours: a
      randomized, double-blind, four-arm trial in adults undergoing abdominal surgery.
AB  - BACKGROUND: Intense pain in the first 12 hours after major abdominal surgery
      requires the use of large amounts of analgesics, mainly opioids, which may
      produce undesirable effects. Buprenorphine (BUP) is not typically used
      intravenously in this setting, particularly in combination with morphine (MO),
      due to concerns that BUP might inhibit the analgesic effect of MO. OBJECTIVE:
      This study compared the analgesic effect of BUP and MO separately and in
      combination for postoperative pain control in patients undergoing abdominal
      surgery. METHODS: In this double-blind study, adult patients were randomized to
      receive 1 of 4 regimens for 12 hours: a basal BUP infusion (BUP-i) of 0.4
      microg/kg/h + BUP boluses (BUP-b) of 0.15 microg/kg each; a basal MO infusion (MO
      i) of 10 microg/kg/h + MO boluses (MO-b) of 5 microg/kg each; a basal BUP-i of
      0.4 microg/kg/h + MO-b of 5 microg/kg each; or a basal MO-i of 10 microg/kg/h +
      BUP-b of 0.15 microg/kg each. Bolus doses were delivered by intravenous patient
      controlled anesthesia, with a bolus lockout time of 7 minutes. Diclofenac 75 mg
      IM q6h was available as rescue pain medication. Every 15 minutes during the first
      2 postoperative hours and hourly thereafter, patients used visual analog scales
      to rate their pain (from 0 = totally free of pain to 10 = unbearable pain), level
      of sedation (from 1 = totally awake to 10 = heavily sedated), and satisfaction
      with treatment (from 1 = totally unsatisfied to 10 = fully satisfied). Blood
      pressure, heart rate, respiration rate, and arterial blood oxygen saturation
      (SpO(2)) were monitored, and adverse effects reported by patients or noted by
      clinicians were recorded at the same times. Study end points included total
      opioid consumption (infusion + boluses), demand:delivery ratio, and use of rescue
      medication. RESULTS: One hundred twenty patients (63 men, 57 women; age range, 21
      80 years; weight range, 40-120 kg) were included in the study. Seventy-four
      percent had other mild, treated diseases (American Society of Anesthesiologists
      physical class 2). Pain visual analog scale ratings were comparably high in all
      groups during the first 2 postoperative hours. Pain intensity ratings at 3 to 12
      hours were significantly lower in those who received BUP-i + BUP-b compared with
      the other treatment groups (P = 0.018). The drug requirement during the
      postoperative period decreased significantly in all groups (P = 0.01); however,
      there was a significant difference between groups in the demand:delivery ratio at
      3 to 12 hours (group * psydrug interaction, P = 0.026). The numerically lowest
      demand:delivery ratio was seen with BUP-i + BUP-b. BUP-i was associated with a
      significantly lower heart rate compared with the other groups (P = 0.027); there
      were no drug-related differences in respiration rate, SpO(2), or sedation.
      Patients' level of satisfaction with treatment was significantly higher in the
      group that received BUP-i + BUP-b compared with the other 3 groups (P < 0.001).
      Postoperative nausea and vomiting were mild and occurred at a similar incidence
      in all groups, as did rescue diclofenac use. CONCLUSIONS: In these patients
      undergoing abdominal surgery, the BUP-i + BUP-b regimen controlled postoperative
      pain as well as did MO-i + MO-b or the combinations of BUP and MO. BUP neither
      inhibited the analgesia provided by MO nor induced undesired sedation or
      hemodynamic or respiratory effects.

PMID- 19393844
TI  - Topiramate versus amitriptyline in migraine prevention: a 26-week, multicenter,
      randomized, double-blind, double-dummy, parallel-group noninferiority trial in
      adult migraineurs.
AB  - OBJECTIVE: The primary objective of this study was to compare the efficacy and
      tolerability of topiramate and amitriptyline in the prophylaxis of episodic
      migraine headache. METHODS: This was a 26-week, multicenter, randomized, double
      blind, double-dummy, parallel-group noninferiority study. Adults with 3 to 12
      migraines per month were randomized in a 1:1 ratio to receive an initial dose of
      25 mg/d of either topiramate or amitriptyline, subsequently titrated to a maximum
      of 100 mg/d (or the maximum tolerated dose). The primary efficacy outcome was the
      change from prospective baseline in the mean monthly number of migraine episodes.
      Secondary efficacy variables included changes from the prospective baseline phase
      to the end of the double-blind phase in the mean monthly (28-day) rate of days
      with migraine, mean monthly rate of days with headache (migraine and
      nonmigraine), mean monthly rate of acute abortive medication use, mean monthly
      migraine duration, and mean monthly migraine severity. Additional secondary
      efficacy variables included changes in the mean monthly severity of migraine
      associated symptoms (photophobia, phonophobia, and nausea), change in the mean
      monthly frequency f migraine-associated vomiting, and response rates (based on
      monthly migraine days and total headache days). The Migraine-Specific Quality of
      Life Questionnaire (MSQ) and the Weight Satisfaction Scale Questionnaire, which
      measures subjective satisfaction with current weight, were administered.
      Treatment-emergent adverse events (TEAEs) were monitored through the end of
      double-blind treatment. RESULTS: The intent-to-treat population included 331
      subjects (172 topiramate, 159 amitriptyline; 84.9% female; 84.6% white; mean [SD]
      age, 38.8 [11.0] years; mean weight, 77.1 [20.1] kg) who provided at least 1
      efficacy assessment. The least squares mean (LSM) change from baseline in the
      mean monthly number of migraine episodes was not significantly different between
      the topiramate and amitriptyline groups (-2.6 and -2.7, respectively; 95% CI, 
      0.6 to 0.7). There were no significant differences between treatment groups in
      any of the prespecified secondary outcome measures. Subjects receiving topiramate
      had a significantly greater improvement in mean functional disability scores
      during migraine attacks compared with amitriptyline (LSM change: -0.33 vs -0.19;
      95% CI, -0.3 to 0.0; P = 0.040) and in the role function-restrictive, role
      function-preventive, and emotional function domains of the MSQ (P = 0.012, P =
      0.014, and P = 0.029, respectively). Subjects receiving topiramate had a mean
      weight loss of 2.4 kg, compared with a mean weight gain of 2.4 kg in subjects
      receiving amitriptyline. Subjects in the topiramate group reported an overall
      improvement from baseline in weight satisfaction, whereas the amitriptyline group
      reported an overall deterioration in weight satisfaction (P < 0.001, topiramate
      vs amitriptyline). TEAEs of mild or moderate severity were reported in 118
      subjects (66.7%) in the topiramate group and 112 subjects (66.3%) in the
      amitriptyline group. Among the most common TEAEs (reported in +/-5% of subjects
      during the double-blind phase) in the topiramate group were paresthesia (29.9%),
      fatigue (16.9%), somnolence (11.9%), hypoesthesia (10.7%), and nausea (10.2%).
      The most commonly reported TEAEs in the amitriptyline group were dry mouth
      (35.5%), fatigue (24.3%), somnolence (17.8%), weight increase (13.6%), dizziness
      (10.7%), and sinusitis (10.7%). CONCLUSIONS: In this noninferiority study,
      topiramate was at least as effective as amitriptyline in terms of reducing the
      rate of mean monthly migraine episodes and all prespecified secondary efficacy
      end points. Topiramate was associated with improvement in some quality-of-life
      indicators compared with amitriptyline and was associated with weight loss and
      improved weight satisfaction.

PMID- 19393845
TI  - Effects of combination treatment with ketoprofen 100 mg + acetaminophen 1000 mg
      on postoperative dental pain: a single-dose, 10-hour, randomized, double-blind,
      active- and placebo-controlled clinical trial.
AB  - BACKGROUND: A combination of analgesic drugs with different pharmacologic
      properties may be more effective, with fewer adverse events, than either agent
      used alone. OBJECTIVE: This study assessed whether the combination of
      acetaminophen and ketoprofen is more effective and better tolerated than either
      drug used alone in treating postoperative pain. METHODS: This single-dose
      randomized, double-blind, active- and placebo-controlled study was conducted at
      the Finnish Student Health Service, Oulu, Finland. Patients aged 18 to 40 years
      with moderate or severe pain (>or=3 on a numerical rating scale [NRS] of 0-10)
      after surgical removal of impacted third molars were randomly assigned to receive
      one of the following drugs in single oral doses: ketoprofen 100 mg +
      acetaminophen 1000 mg, ketoprofen 100 mg, acetaminophen 1000 mg, or placebo
      tablets. Effectiveness was assessed by the onset of analgesia, pain intensity
      difference (PID) from baseline, sum of PID (SPID), and duration of analgesic
      effect. Patients rated pain intensity on the NRS at rest and on dry swallowing.
      Onset of pain relief was measured using time to PID in >or=1 category at rest or
      on dry swallowing (PID >or=1). Patients recorded the occurrence of adverse events
      and the supplemental consumption of rescue medication (ibuprofen). RESULTS: The
      study included 76 patients, accounting for 78 cases (2 patients were operated on
      twice and were assessed as 4 individual patients) (59% women, 41% men; mean age,
      22.8 years; white race, 100%; and mean weight, 68.3 kg). At 1.5 hours, mean SPIDs
      at rest and on swallowing were significantly greater in the combination group
      than in the acetaminophen, ketoprofen, and placebo groups (all, P < 0.05). Mean
      time to onset of pain relief (PID >or=1) at rest and on swallowing were
      significantly less in the combination group than the acetaminophen, ketoprofen,
      and placebo groups (all, P < 0.05). Median time to use of rescue medication was
      significantly longer in the combination group than in the acetaminophen group (P
      = 0.006) and the placebo group (P < 0.001) but not the ketoprofen group. At 1.5
      hours after administration, maximum sedation scores were not significantly
      different between the study groups. The prevalences of trismus, bleeding, and
      edema were not significantly different between the study groups. CONCLUSIONS: The
      results from this study suggest that the combination of ketoprofen 100 mg +
      acetaminophen 1000 mg provided a significantly more rapid onset of analgesia than
      either drug given alone in the management of pain after oral surgery in this
      patient population. Adverse events were not significantly different between the
      study groups. These results support the clinical practice of combining ketoprofen
      with acetaminophen for the management of acute pain.

PMID- 19393846
TI  - Severe insulin allergy after percutaneous transluminal coronary angioplasty.
AB  - BACKGROUND: Insulin therapy is essential for type 1 and inadequately controlled
      type 2 diabetic patients. Insulin allergies have become less common since the
      introduction of highly purified human recombinant insulin. There are rare reports
      of severe insulin allergic reactions after percutaneous transluminal coronary
      angioplasty (PTCA) in patients with type 2 diabetes who had no previous allergic
      reactions. To better understand the causes and presentation of this rare acute
      reaction, we present the following observed case. CASE SUMMARY: A 63-year-old
      Chinese man (height, 172 cm; weight, 68.5 kg) with a 17-year history of type 2
      diabetes and hypertension was first admitted to the West China Hospital, Sichuan
      University, Sichuan, People's Republic of China, for uncontrolled type 2
      diabetes. He used regular human insulin, neutral protamine Hagedorn insulin, or
      premixed insulin without any allergic reactions. Four months later, PTCA was
      performed because of an acute myocardial infarction. The patient was administered
      50 mg of protamine after active abdominal bleeding due to a right external iliac
      artery rupture. Three months later, recurrent raised, pruritic erythema occurred
      at the insulin injection site immediately after injection. Four weeks later, he
      experienced an attack of generalized urticaria at multiple previous injection
      sites (abdomen, upper arms, thighs) after injecting premixed insulin. It was
      accompanied by dizziness and palpitations. During the following 3 months, the
      symptoms recurred 3 times; one time, the patient reported losing consciousness
      for 2 to 3 minutes. The results of a skin prick test found that he was allergic
      to human recombinant insulin and insulin lispro. The allergy was resolved by
      changing his treatment regimen from insulin to oral hypoglycemic agents. A
      Naranjo score of 10 suggested a definite relationship (score >or=9) between the
      adverse drug reaction and the insulin administration. CONCLUSIONS: We present a
      definite case of allergy associated with insulin and insulin lispro
      administration. The patient had not experienced anaphylactic reactions prior to
      PTCA and protamine administration.

PMID- 19393847
TI  - Effects of pitavastatin on cerebral blood flow.
AB  - BACKGROUND: Hypercholesterolemia has been identified as an important risk factor
      for stroke. It has been reported that statins might reduce the risk for new or
      recurrent cardiovascular events and strokes. OBJECTIVE: This paper reports on the
      effects of pitavastatin on cerebral blood flow in 2 elderly patients. CASE
      SUMMARY: Two patients, a 72-year-old right-handed Japanese man and a 77-year-old
      right-handed Japanese woman, both with a history of cerebral infarction, received
      6-month treatment with pitavastatin 2 mg/d for complicated hypercholesterolemia.
      To assess regional cerebral blood flow (rCBF), single-photon emission computed
      tomography (SPECT) studies with technetium-99m-ethyl cysteinate dimer were
      carried out before and after pitavastatin administration. Tomography was
      evaluated using the Easy z Score Imaging System. None of the patients' other
      treatments, with the exception of pitavastatin initiation, were modified during
      the treatment period. In both patients, serum total cholesterol concentrations
      were improved within 3 months of initiation of pitavastatin treatment, with no
      marked changes in clinical symptoms. In both patients, improvement was found in
      rCBF on SPECT. The z score of the left parietal lobe in 1 patient was improved,
      from 2.20 to 1.69. That of the other patient was also improved, from 2.42 to
      1.94. CONCLUSION: In both patients, clinically significant improvement in rCBF
      was found after 6-month treatment with pitavastatin 2 mg/d.

PMID- 19393848
TI  - Drug rash with eosinophilia and systemic signs syndrome in a patient with
      multiple sclerosis.
AB  - INTRODUCTION: Drug rash with eosinophilia and systemic signs (DRESS) syndrome is
      defined by the triad of fever, dermatitis, and internal organ involvement,
      characteristically occurring with a delay of 3 to 8 weeks after the initiation of
      treatment with the associated drug. We describe a case of DRESS syndrome in a
      patient with multiple sclerosis (MS), characterized by a very high eosinophilia
      and cholestatic hepatitis. CASE SUMMARY: A 44-year-old white woman with primary
      progressive MS receiving a multidrug of PO baclofen 75 mg/d, PO piracetam 3 g/d,
      and IV mitoxantrone 10 mg administered once a month presented to the Multiple
      Sclerosis Center, University of Catania, Catania, Italy. Eight weeks after the
      introduction of the latter 2 drugs, the patient had clinical and histological
      signs of severe cholestatic syndrome followed by hypereosinophilia. All
      treatments were stopped on admission. Laboratory tests (serologic viral markers,
      autoantibody pattern antinuclear autoantibodies, antismooth muscle
      autoantibodies, antimitochondrial autoantibodies, antineutrophil-cytoplasmic
      autoantibodies, antiliver-kidney-microsomes), abdomen ultrasound, and magnetic
      resonance cholangiopancreatography did not reveal a cause of the cholestatic
      syndrome. A liver biopsy was performed because of the persistence of the clinical
      signs. A Naranjo rating of 4 suggested that mitoxantrone was possibly associated
      with the occurrence of DRESS. Six months after the first symptoms of DRESS
      appeared, laboratory tests were normal. Although there are few diagnostic methods
      for confirming an adverse drug hypersensitivity reaction, a skin prick test
      suggested a marked positivity for mitoxantrone at all concentrations (100%, 50%,
      10%). During the first 72 hours, reaction was characterized by skin edema,
      erythema, and itchiness in the site of inoculation of the drug. The local
      reaction started to regress after 72 hours, with a complete restitution ad
      integrum in 6 days. A blue discoloration of skin remained for an additional 13
      days. CONCLUSION: We report a case of DRESS syndrome possibly associated with
      mitoxantrone in a patient with MS.

PMID- 19393849
TI  - A single-center, open-label, one-sequence study of dalcetrapib coadministered
      with ketoconazole, and an in vitro study of the S-methyl metabolite of
      dalcetrapib.
AB  - BACKGROUND: Dalcetrapib (RO4607381/JTT-705) is currently under clinical
      investigation for the prevention of cardiovascular events. It inhibits the
      activity of cholesteryl ester transfer protein and has been reported to increase
      levels of high-density lipoprotein cholesterol. OBJECTIVE: Because dalcetrapib is
      likely to be coadministered with agents that inhibit the cytochrome P450 (CYP)
      3A4 isozyme, this study aimed to determine the effect of ketoconazole, a strong
      CYP3A4 inhibitor, on the pharmacokinetics of dalcetrapib. METHODS: An open-label,
      1-sequence study was conducted in 2 cohorts of healthy, nonsmoking male
      volunteers aged 18 through 65 years, with a body mass index of 18 to 32 kg/m(2).
      The first cohort received dalcetrapib 600 mg on days 1 and 7 and ketoconazole 400
      mg on days 2 through 7, and, based on the results of a planned interim analysis,
      the second cohort received dalcetrapib 900 mg alone on days 1 and 7 and
      ketoconazole on days 2 through 7. Pharmacokinetic and safety parameters were
      assessed at specific times throughout the study. To confirm CYP involvement in
      the metabolism of the inactive metabolite dalcetrapib-S-methyl, in vitro studies
      were performed using human liver microsomes and recombinantly expressed CYP
      isoforms. RESULTS: Of the 26 participants, 96% were white, with a mean age of
      38.1 years and a mean weight of 78.6 kg. In the in vivo portion of the study,
      coadministration of ketoconazole with dalcetrapib 600 mg had no significant
      effect on any pharmacokinetic parameter of dalcetrapib. Coadministration of
      ketoconazole with dalcetrapib 900 mg was associated with significant decreases in
      the dalcetrapib C(max) (-23%; P = 0.002) and AUC(0-infinity) (-18%; P = 0.001)
      and a significant increase in oral clearance (22%; P = 0.001). Significant
      increases in the C(max) (P = 0.001) and AUC(0-infinity) (P < 0.001) of
      dalcetrapib-S-methyl were observed with coadministration of ketoconazole. The
      combination was generally well tolerated, with 32 of 35 adverse events (91.4%)
      being mild in intensity. The most frequent adverse events were headache (6/26
      [23.1%] in the ketoconazole group; 4/18 [22.2%] in the group receiving
      dalcetrapib 900 mg plus ketoconazole) and diarrhea (4/26 [15.4%] in the
      ketoconazole group; 2/18 [11.1%] in the group receiving dalcetrapib 900 mg plus
      ketoconazole). The in vitro studies confirmed the involvement of CYP3A in the
      metabolism of dalcetrapib-S-methyl. CONCLUSIONS: In this clinical study in
      healthy male volunteers, coadministration of dalcetrapib 600 mg with the CYP3A4
      inhibitor ketoconazole was not associated with any significant changes in the
      pharmacokinetic parameters of the parent compound. Coadministration of
      dalcetrapib 900 mg with ketoconazole was associated with significant decreases in
      the dalcetrapib C(max) and AUC, contrary to the increases that would be expected
      if dalcetrapib were a substrate for CYP3A4. The combination of dalcetrapib and
      ketoconazole was generally well tolerated.

PMID- 19393850
TI  - A single-dose, randomized, two-way crossover study comparing two olanzapine
      tablet products in healthy adult male volunteers under fasting conditions.
AB  - BACKGROUND: Olanzapine is a psychotropic agent that belongs to the
      thienobenzodiazepine class. OBJECTIVE: The aim of this study was to assess the
      bioequivalence of 2 commercial 10-mg tablet formulations of olanzapine by
      statistical analysis of the pharmacokinetic parameters C(max), AUC from 0 to 72
      hours after dosing (AUC(0-72)), and AUC(0-infinity) as required by the Egyptian
      health authority for the marketing of a generic product. METHODS: This
      bioequivalence study was carried out in healthy male volunteers using a single
      dose, randomized, 2-way crossover design under fasting conditions. Statistical
      analysis of the pharmacokinetic parameters C(max), AUC(0-72), and AUC(0-infinity)
      was conducted to determine bioequivalence (after log-transformation of data using
      analysis of variance and 90% CIs) and to gain marketing approval in Egypt. The
      formulations were considered to be bioequivalent if the log-transformed ratios of
      the 3 pharmacokinetic parameters were within the predetermined bioequivalence
      range (ie, 80%-125%), as established by the US Food and Drug Administration
      (FDA). Both the test product (Trademark: Integrol((R)) [Global Napi
      Pharmaceuticals, Cairo, Egypt]) and the reference product (Trademark:
      Zyprexa((R)) [Eli Lilly and Company, Basingstoke, Hampshire, United Kingdom])
      were administered as 10-mg tablets with 240 mL of water after an overnight fast
      on 2 treatment days, separated by a 2-week washout period. After dosing, serial
      blood samples were collected for 72 hours. Plasma samples were analyzed using a
      sensitive, reproducible, and accurate liquid chromatography-tandem mass
      spectrometry method capable of quantitating olanzapine in the range of 0.167 to
      16.7 ng/mL, with a lower limit of quantitation of 0.167 ng/mL. Adverse events
      were reported by the volunteers as instructed or observed by the resident
      physician, and were recorded, tabulated, and evaluated. RESULTS: Twenty-four
      healthy adult male volunteers participated in this study. Their mean (SD) age was
      24.7 (6.2) years (range, 19-41 years), mean weight was 73.4 (6.7) kg (range, 64
      89 kg), and mean height was 174.25 (4.6) cm (range, 168-186 cm). Values for
      C(max), AUC(0-72), AUC(0-infinity), T(max), t(1/2), and the terminal disposition
      rate constant were found to be in agreement with previously reported values. The
      differences between the 2 products did not reach statistical significance at P
      <or= 0.05 (90% CIs: C(max), 101.82-124.79; AUC(0-72), 93.36-102.04; and AUC(0
      infinity), 88.57-101.77). The test/reference ratio of these parameters was within
      the acceptance range of the FDA criterion for bioequivalence. Both formulations
      were apparently well absorbed from the gastrointestinal tract (ie, no specific
      gastrointestinal tract-related adverse events were reported). CONCLUSIONS: In
      this small study in healthy male volunteers, there were no statistically
      significant differences in any of the calculated pharmacokinetic parameters
      between the 10-mg test and reference tablets of olanzapine. The 90% CIs for the
      ratios of mean C(max), AUC(0-72), and AUC(0-infinity) were within the range of
      80% to 125% (using log-transformed data), meeting the FDA regulatory criterion
      for bioequivalence. Both formulations were well tolerated.

PMID- 19393851
TI  - An open-label, single-dose, parallel-group, dose-increasing study comparing the
      pharmacokinetics and tolerability of pilsicainide hydrochloride in healthy Korean
      and Japanese male subjects.
AB  - BACKGROUND: Pilsicainide hydrochloride is a class IC antiarrhythmic agent used
      for the treatment of supraventricular and ventricular arrhythmias. OBJECTIVE: The
      objective of this study was to compare the pharmacokinetics and tolerability of
      pilsicainide in healthy Korean and Japanese male volunteers to satisfy regulatory
      requirements for marketing pilsicainide in the Republic of Korea. METHODS: This
      was an open-label, single-dose, parallel-group, dose-increasing study. It was
      simultaneously conducted in healthy Korean and Japanese volunteers from September
      2005 through May 2006; pilsicainide was approved for use in the Republic of Korea
      in 2007. Subjects for the 100-mg group were enrolled after the performance of
      tolerability evaluations in the 50-mg dose group. Serial blood and urine samples
      were collected up to 24 hours after dosing, and drug concentrations in plasma and
      urine were determined by high-performance liquid chromatography. Tolerability was
      evaluated by monitoring adverse events (AEs), clinical laboratory parameters, and
      results of 12-lead electrocardiograms (ECGs). RESULTS: Sixteen healthy Korean
      male subjects (mean [SD] age, 24.5 [4.2] years; weight, 71.8 [5.5] kg; height,
      176.6 [6.3] cm) and 16 healthy male Japanese subjects (age, 24.7 [4.9] years;
      weight, 60.2 [4.4] kg; height, 171.9 [6.4] cm) were enrolled in the study. Values
      for AUC and C(max) of pilsicainide increased proportionally with dose escalation
      in all subjects. Pilsicainide reached C(max) 0.5 to 1.5 hours after dosing in
      both the Korean and Japanese subjects. The mean (SD) dose-normalized values for
      C(max) for the Korean and Japanese subjects were 9.4 (1.9) and 9.2 (1.6)
      ng/mL/mg, respectively. The mean (SD) dose-normalized values for AUC(0-infinity)
      were 56.0 (8.0) ng . h/mL/mg in the Korean subjects and 53.8 (8.1) ng . h/mL/mg
      in the Japanese subjects. None of these findings were statistically significant.
      A total of 9 AEs occurred in 7 of the 16 Korean subjects; they included
      dizziness, feeling of being hot, somnolence, and atrioventricular block. All of
      the AEs were mild in severity and were considered possibly related to
      pilsicainide. Two of the 16 Japanese subjects had a total of 4 AEs. All of the
      AEs occurred in the subjects treated with 50 mg. Of the 2 subjects with AEs, 1
      subject had a decrease in blood pressure, a sense of discomfort, and PR-interval
      prolongation on ECG, while the other developed a premature ventricular
      contraction (PVC). The PR-interval prolongation and PVC were determined to be
      possibly related to pilsicainide, and these were mild in severity. The other AEs
      (ie, decreased blood pressure, sense of discomfort) were moderate in severity.
      CONCLUSIONS: The results of this study suggest that the pharmacokinetic profile
      of pilsicainide was not significantly different between these healthy Korean and
      Japanese male volunteers. A single dose (50 or 100 mg) of pilsicainide was well
      tolerated in both ethnic groups.

PMID- 19393852
TI  - Have we witnessed the rise and fall of race-specific drugs?

PMID- 19393853
TI  - A comparison of insulin use, glycemic control, and health care costs with insulin
      detemir and insulin glargine in insulin-naive patients with type 2 diabetes.
AB  - OBJECTIVES: The goal of this study was to compare daily insulin use, glycemic
      control, and health care costs in insulin-naive patients with type 2 diabetes who
      initiated treatment with either insulin detemir or insulin glargine. METHODS:
      This was a retrospective cohort analysis of health care claims data and
      laboratory results for adult, insulin-naive patients with type 2 diabetes who
      were enrolled in a large US managed care organization and initiated basal therapy
      with insulin detemir or insulin glargine between May 1, 2006, and December 31,
      2006. The daily average consumption (DACON) of insulin was calculated as the
      total number of units dispensed (excluding the last fill) divided by the number
      of days between the index date and the date of the last fill of the index
      insulin. Glycemic control was evaluated by comparing mean glycosylated hemoglobin
      (HbA(1c)) values in the preindex period (the 180 days before the index date) and
      the follow-up period (the 180 days after the index date). Mean all-cause and
      diabetes-related health care costs in the preindex and follow-up periods were
      calculated and compared. RESULTS: The analysis included 48 patients initiating
      therapy with insulin detemir and 258 initiating therapy with insulin glargine.
      The mean age of the 2 cohorts was approximately 54 years, and most patients in
      each cohort were male (52.1% and 59.7%, respectively). Few patients in either
      cohort had a baseline HbA(1c) value <7% (13% and 10%), suggesting poor glycemic
      control at the time of insulin initiation. After adjustment for confounders (eg,
      preindex diabetes medication), the DACON of insulin was comparable between
      cohorts (29.3 and 29.6 U/d; P = NS), as were follow-up HbA(1c) values (8.2% and
      7.9%). Insulin detemir and insulin glargine also were associated with comparable
      mean adjusted all-cause pharmacy costs ($3074 and $2899), medical costs ($2319
      and $3704), and total health care costs ($6014 and $7023). However, insulin
      glargine was associated with significantly higher mean adjusted diabetes-related
      medical costs compared with insulin detemir ($1510 vs $707, respectively; P =
      0.03), as well as significantly higher mean adjusted total diabetes-related
      health care costs ($3408 vs $2261; P = 0.03). CONCLUSIONS: In this managed care
      population of insulin-naive patients who initiated therapy with insulin detemir
      or insulin glargine, the daily insulin dose and glycemic control did not differ
      significantly between the 2 insulins. However, patients receiving insulin detemir
      incurred lower diabetes-related medical and total health care costs.

PMID- 19393854
TI  - Effectiveness of hydralazine/isosorbide dinitrate in racial/ethnic subgroups with
      heart failure.
AB  - BACKGROUND: The addition of hydralazine/isosorbide dinitrate (H-ISDN) to a
      standard heart failure treatment regimen in the African-American Heart Failure
      Trial was associated with a 43% reduction in mortality. However, the
      effectiveness of H-ISDN in a community sample of African-American patients and
      other racial/ethnic groups is unknown. OBJECTIVE: The aim of this study was to
      assess the associations between treatment with H-ISDN and mortality or
      hospitalization for heart failure in veterans with the disease. METHODS: For this
      retrospective cohort study, electronic data on outpatient prescriptions,
      comorbidity, and other heart failure risk factors were analyzed in veterans with
      heart failure. Patients were classified based on whether they were prescribed H
      ISDN and subclassified based on race/ethnicity (African American, Hispanic, or
      white). Patients who were prescribed H-ISDN were subclassified based on time of
      initiation of H-ISDN treatment (0-121, 122-365, or >365 days after diagnosis).
      Data were analyzed using propensity-adjusted Cox regression analyses, with
      exposure to H-ISDN modeled as a time-varying covariate. RESULTS: Data from 76,828
      veterans were analyzed (98% men, 2% women). H-ISDN prescription was not
      associated with the risk of death in 5 of the 9 subgroups predefined by
      race/ethnicity or time of initiation of H-ISDN; however, H-ISDN was associated
      with an increased risk of death in the 4 subgroups with longer times to
      initiation. H-ISDN was associated with a significantly increased risk of heart
      failure hospitalization in all but 1 of the 9 subgroups. The risk of both
      mortality and hospitalization associated with H-ISDN was significantly lower in
      African-American patients than in those who were Hispanic or white. Concurrent
      prescription of other, evidence-based heart failure therapies (eg, angiotensin
      converting enzyme inhibitors, beta-blockers, and combinations) had strong,
      statistically significant associations with reduced mortality. CONCLUSIONS: In
      this population of veterans with heart failure, H-ISDN prescription was not
      associated with significant reductions in mortality or hospitalization in any of
      the subgroups defined by race/ethnicity and time of initiation of H-ISDN analyzed
      compared with the group that did not receive H-ISDN. It is possible, or even
      likely, that unmeasured differences in important risk factors-particularly heart
      failure severity and left ventricular dysfunction-between the group that received
      H-ISDN and the one that did not masked a beneficial effect of H-ISDN. Therefore,
      our conclusions must be regarded as hypothesis generating and need to be tested
      in subsequent randomized trial(s).

PMID- 19393855
TI  - Results of a retrospective claims database analysis of differences in
      antidepressant treatment persistence associated with escitalopram and other
      selective serotonin reuptake inhibitors in the United States.
AB  - BACKGROUND: Although previous studies have found no differences in response to
      antidepressant pharmacotherapy between selective serotonin reuptake inhibitors
      (SSRIs), some recent trials suggest benefits associated with more rapid onset of
      action. OBJECTIVE: The aim of this work was to compare the likelihood that
      patients initiating treatment with branded escitalopram, rather than with any of
      3 SSRIs (ie, citalopram, fluoxetine, and paroxetine) that are available in
      generic or branded formulations, would continue therapy with the initial
      medication after 2 and 6 months. METHODS: We used propensity score-weighted
      logistic regression to assess the effect of antidepressant choice on the
      likelihood of continuing treatment, based on data from a large administrative
      claims database with information about US patients. We modeled the propensity to
      initiate treatment with escitalopram based on demographic, diagnostic, insurance,
      and service-use characteristics in the 6 months before treatment initiation and
      used the results to calculate weights for analysis of treatment continuation. The
      primary outcome measures were receipt of 2 prescriptions of the index drug in the
      first 2 months and, among those continuing at 2 months, 4 prescriptions in the
      first 6 months. Antidepressant choice, cost, and service-use characteristics
      during the treatment period were included as covariates. Patients who initiated
      therapy between July 2002 and April 2005 were eligible for inclusion. RESULTS:
      Based on data for 43,921 patients, at 2 months, escitalopram initiators were more
      likely to have continued initial medication than those receiving the other SSRIs
      (66.1% vs 61.9%, respectively; P < 0.01) and less likely to have switched or
      augmented treatment (4.8% vs 7.6%; P < 0.01). At 6 months, escitalopramtreated
      patients were also more likely to have continued initial medication (47.1% vs
      41.0%; P < 0.01) and less likely to have switched or augmented treatment (9.4% vs
      14.4%; P < 0.01). CONCLUSION: Patients initiating treatment with escitalopram
      were more likely to continue and less likely to switch or augment treatment at 2
      and 6 months of therapy compared with those who initiated with alternative SSRIs.

PMID- 19393856
TI  - Health economic comparison between continuous subcutaneous insulin infusion and
      multiple daily injections of insulin for the treatment of adult type 1 diabetes
      in Canada.
AB  - BACKGROUND: Patients with type 1 diabetes mellitus (DM) may be treated with
      insulin via multiple daily injections (MDI) or continuous subcutaneous insulin
      infusion (CSII). OBJECTIVE: The purpose of this study was to evaluate the
      projected long-term cost-effectiveness of CSII compared with MDI by modeling a
      simulated sample of adult patients with type 1 DM in Canada. METHODS: A health
      economic model was used to determine the incremental cost-effectiveness ratio
      (ICER) of CSII compared with MDI from the perspective of a Canadian provincial
      government. The primary input variable was change in glycosylated hemoglobin
      (HbA(1c)). A series of Markov constructs also simulated the progression of
      disease-related complications. Annual acquisition costs for CSII and MDI were
      year-2006 Can $6347.18 and Can $4649.69, respectively. A 60-year time horizon and
      a discount rate of 5.0% per annum on costs and clinical outcomes were used.
      RESULTS: Mean direct lifetime costs were Can $15,591 higher with CSII treatment
      than MDI. Treatment with CSII was associated with an improvement in discounted
      life expectancy of 0.655 quality-adjusted life-years (QALYs) over a 60-year time
      horizon, compared with MDI (mean [SD], 10.029 [0.133] vs 9.374 [0.076] QALYs).
      ICERs were Can $27,264 per life-year gained and Can $23,797 per QALY for CSII
      compared with MDI. The results were most sensitive to HbA(1c) assumptions.
      CONCLUSION: Based on this analysis, CSII may be a cost-effective treatment option
      when compared with MDI in adult patients with type 1 DM in Canada.

PMID- 19393857
TI  - New chemical entities and their market penetration in Finland during the years
      1996 through 2005.
AB  - BACKGROUND: There is little empirical information about the role of new chemical
      entities (NCEs) and to what extent they are being adopted in modern health care.
      OBJECTIVE: We aimed to investigate which NCEs were launched in Finland during the
      years 1996 through 2005 and how they penetrated the market in Finland. METHODS:
      NCEs were identified from Finnish drug compendiums and verified from marketing
      authorization and drug wholesale databases. Market penetration was determined by
      extracting data about outpatient drug costs and consumption in the year 2005 from
      drug wholesale databases. RESULTS: Of the 294 NCEs introduced in 1996 through
      2005, 55% were authorized nationally and 45% by the European Commission. Two
      hundred two NCEs (69%) had pharmacy sales in 2005. Most NCEs were for cancer
      (19), infections (18), cardiovascular diseases (17), and pain and arthritis (14).
      NCEs introduced from 1996 through 2005 comprised 38% of total outpatient
      prescription drug costs and 19% of the total volume of NCEs used by outpatients
      in 2005. The corresponding figures for the NCEs introduced in 2001 through 2005
      were 11% and 4%. All drugs for dementia and multiple sclerosis, all biological
      drugs for rheumatoid arthritis, and most drugs for erectile dysfunction and
      osteoporosis were introduced during the study period. The cost of NCEs also
      accounted for >50% of costs for drugs to treat hyperlipidemia, peptic ulcer,
      psychosis, and diabetes mellitus. CONCLUSIONS: The use of NCEs was greater when
      measured in monetary value than in volume. The overall costs of NCEs introduced
      from 1996 through 2005 were high in several major drug classes, although their
      share of overall use was modest when measured in volume. The market penetration
      of drugs introduced during 2001 through 2005 was still rather low in 2005.

PMID- 19393859
TI  - Dopamine D4 receptor gene exon III polymorphism associated with binge drinking
      attitudinal phenotype.
AB  - Although binge drinking is a serious public health problem, relatively few
      studies have investigated the relationship between specific dopaminergic genes
      such as the dopamine D4 receptor (DRD4) and binge drinking attitudinal
      phenotypes. This study used the DNA subsample (N=233, mean age 19.8, standard
      deviation,0.89) of the National Longitudinal Study of Adolescent Health to
      investigate the association between a 48 base-pair variable number of tandem
      repeats in the DRD4 gene and a measure of binge drinking. Multivariate regression
      models indicated that the 7-repeat (7R) allele of the exon III polymorphism is
      significantly positively associated (beta=0.16, P<.05) with binge drinking while
      controlling for low self-control and demographic variables. Findings were sturdy
      across race and gender. The present study provides unique evidence to the genetic
      underpinnings of binge drinking. Results suggest that the 7R allele may be an
      important contributor to the liability to binge drinking.

PMID- 19393860
TI  - The anxiolytic etifoxine protects against convulsant and anxiogenic aspects of
      the alcohol withdrawal syndrome in mice.
AB  - Change in the function of gamma-aminobutyric acid(A) (GABA(A)) receptors
      attributable to alterations in receptor subunit composition is one of main
      molecular mechanisms with those affecting the glutamatergic system which
      accompany prolonged alcohol (ethanol) intake. These changes explain in part the
      central nervous system hyperexcitability consequently to ethanol administration
      cessation. Hyperexcitability associated with ethanol withdrawal is expressed by
      physical signs, such as tremors, convulsions, and heightened anxiety in animal
      models as well as in humans. The present work investigated the effects of
      anxiolytic compound etifoxine on ethanol-withdrawal paradigms in a mouse model.
      The benzodiazepine diazepam was chosen as reference compound. Ethanol was given
      to NMRI mice by a liquid diet at 3% for 8 days, then at 4% for 7 days. Under
      these conditions, ethanol blood level ranged between 0.5 and 2 g/L for a daily
      ethanol intake varying from 24 to 30 g/kg. These parameters permitted the
      emergence of ethanol-withdrawal symptoms once ethanol administration was
      terminated. Etifoxine (12.5-25 mg/kg) and diazepam (1-4 mg/kg) injected
      intraperitoneally 3h 30 min after ethanol removal, decreased the severity in
      handling-induced tremors and convulsions in the period of 4-6h after withdrawal
      from chronic ethanol treatment. In addition when administered at 30 and 15 min,
      respectively, before the light and dark box test, etifoxine (50mg/kg) and
      diazepam (1mg/kg) inhibited enhanced aversive response 8h after ethanol
      withdrawal. Etifoxine at 25 and 50 mg/kg doses was without effects on spontaneous
      locomotor activity and did not exhibit ataxic effects on the rota rod in animals
      not treated with ethanol. These findings demonstrate that the GABAergic compound
      etifoxine selectively reduces the physical signs and anxiety-like behavior
      associated with ethanol withdrawal in a mouse model and may hold promise in the
      treatment of ethanol-withdrawal syndrome in humans.

PMID- 19393861
TI  - Rats in acute withdrawal from ethanol exhibit left ventricular systolic
      dysfunction and cardiac sympathovagal balance shift.
AB  - There is strong evidence that sympathovagal balance plays an important role in
      the progression of cardiac dysfunction in non-alcoholics. The purpose of this
      investigation was to determine whether a pattern of continuous ethanol intake and
      withdrawal modulates the cardiac sympathovagal balance and left ventricular (LV)
      systolic function in rats. Male Wistar rats were treated with a continuous
      ethanol liquid diet for 49 days, and then subjected to 1-day withdrawal and 21
      day abstinence. Cardiac sympathovagal balance and LV systolic function were
      evaluated based on heart rate variability (HRV), Western blotting, and
      echocardiography. Longitudinal data obtained from the same rats showed that the
      49-day continuous ethanol treatment induced LV systolic dysfunction, expressed by
      decreased fractional shortening and ejection fraction. At the 1-day withdrawal,
      LV systolic dysfunction was deteriorated, and the low-frequency power/high
      frequency power (LF/HF) ratio in HRV was elevated because of the depressed HF and
      the increased LF. Western blot analysis showed an increased expression of
      myocardial tyrosine hydroxylase and a decreased expression of myocardial
      acetylcholine. All anomalies were recovered to baseline values with 21-day
      abstinence. We concluded that acute withdrawal from a 49-day continuous ethanol
      regimen is sufficient to promote the shift of cardiac sympathovagal balance
      toward sympathetic predominance and reduced vagal tone, contributing to the
      further deterioration of LV systolic function in rats. Those providing medical
      care for alcoholics should be aware of this enhanced susceptibility to LV
      systolic dysfunction with abrupt termination of a continuous ethanol regimen.

PMID- 19393863
TI  - Alcohol and trauma: a summary of the Satellite Symposium at the 30th Annual
      Meeting of the Shock Society.
AB  - This article highlights the research presented at the Alcohol and Trauma
      Satellite Symposium at the 30th Annual Meeting of the Shock Society. The
      satellite meeting was held on June 8 and 9 in Baltimore, MD. Its purpose was to
      discuss recent findings in the areas of alcohol and injury, including the effect
      of alcohol use on patients in the trauma unit of hospitals. The meeting consisted
      of three sessions, with plenary talks by invited speakers, short talks from
      selected abstracts, and a poster session. Participants presented data on the
      effects of alcohol on organ function, healing, and immune processes after a
      variety of injuries including burn, hemorrhagic shock, sepsis, and ischemia
      reperfusion.

PMID- 19393864
TI  - Fibrin glue-assisted sutureless scleral fixation.

PMID- 19393862
TI  - Ethanol inhibition of aspartyl-asparaginyl-beta-hydroxylase in fetal alcohol
      spectrum disorder: potential link to the impairments in central nervous system
      neuronal migration.
AB  - Fetal alcohol spectrum disorder (FASD) is caused by prenatal exposure to alcohol
      and associated with hypoplasia and impaired neuronal migration in the cerebellum.
      Neuronal survival and motility are stimulated by insulin and insulin-like growth
      factor (IGF), whose signaling pathways are major targets of ethanol
      neurotoxicity. To better understand the mechanisms of ethanol-impaired neuronal
      migration during development, we examined the effects of chronic gestational
      exposure to ethanol on aspartyl (asparaginyl)-beta-hydroxylase (AAH) expression,
      because AAH is regulated by insulin/IGF and mediates neuronal motility. Pregnant
      Long-Evans rats were pair-fed isocaloric liquid diets containing 0, 8, 18, 26, or
      37% ethanol by caloric content from gestation day 6 through delivery. Cerebella
      harvested from postnatal day 1 pups were used to examine AAH expression in
      tissue, and neuronal motility in Boyden chamber assays. We also used cerebellar
      neuron cultures to examine the effects of ethanol on insulin/IGF-stimulated AAH
      expression, and assess the role of GSK-3beta-mediated phosphorylation on AAH
      protein levels. Chronic gestational exposure to ethanol caused dose-dependent
      impairments in neuronal migration and corresponding reductions in AAH protein
      expression in developing cerebella. In addition, prenatal ethanol exposure
      inhibited insulin and IGF-I-stimulated directional motility in isolated
      cerebellar granule neurons. Ethanol-treated neuronal cultures (50mMx96h) also had
      reduced levels of AAH protein. Mechanistically, we showed that AAH protein could
      be phosphorylated on Ser residues by GSK-3beta, and that chemical inhibition of
      GSK-3beta and/or global Caspases increases AAH protein in both control- and
      ethanol-exposed cells. Ethanol-impaired neuronal migration in FASD is associated
      with reduced AAH expression. Because ethanol increases the activities of both GSK
      3beta and Caspases, the inhibitory effect of ethanol on neuronal migration could
      be mediated by increased GSK-3beta phosphorylation and Caspase degradation of AAH
      protein.

PMID- 19393866
TI  - Diffractive intraocular lens power after myopic laser in situ keratomileusis.

PMID- 19393867
TI  - Re: Comparison of a torsional handpiece through microincision versus standard
      clear corneal cataract wounds.

PMID- 19393869
TI  - Postoperative induced myopia in patients with combined vitrectomy and cataract
      surgery.

PMID- 19393873
TI  - Consultation section: refractive surgical problem.

PMID- 19393877
TI  - Deep anterior lamellar keratoplasty with femtosecond-laser zigzag incisions.
AB  - We describe a technique that uses IntraLase-created zigzag incisions for deep
      anterior lamellar keratoplasty. In this technique, the laser creates a precise
      incision that extends to within 70 microm of the recipient Descemet membrane. The
      deep incision minimizes air escape into the peripheral cornea during big-bubble
      formation. In cases that require hand dissection, the deep incision provides a
      reference for gauging the dissection depth. The angled incision edge facilitates
      final stromal excision with scissors. Compared with standard vertical incisions,
      the zigzag incision provides an interlocking wound configuration and facilitates
      matching the donor and recipient anterior surfaces.

PMID- 19393878
TI  - Deep anterior lamellar keratoplasty performed with the femtosecond laser zigzag
      incision for the treatment of stromal corneal pathology and ectatic disease.
AB  - We describe a variation of the big-bubble deep anterior lamellar keratoplasty
      (DALK) technique using the femtosecond laser zigzag incision. This technique
      allows precise depth visualization for air-needle placement in the posterior
      stroma based on the lamellar and posterior laser cuts, thus minimizing the risk
      for perforation of Descemet membrane. The matching donor and host tissue zigzag
      cut allows more precise tissue apposition and greater surface area for healing.
      The angled anterior donor and host junction allows a smooth transition for
      improved visual outcomes. If the big-bubble- Descemet membrane dissection fails,
      the surgeon can convert to a full-thickness graft while retaining the benefits of
      the femtosecond laser incision.

PMID- 19393879
TI  - Canaloplasty: circumferential viscodilation and tensioning of Schlemm canal using
      a flexible microcatheter for the treatment of open-angle glaucoma in adults: two
      year interim clinical study results.
AB  - PURPOSE: To evaluate 2-year postsurgical safety and efficacy of canaloplasty
      (circumferential viscodilation and tensioning of the inner wall of Schlemm canal)
      to treat open-angle glaucoma (OAG). SETTING: Multicenter surgical sites. METHODS:
      This international prospective study comprised adult OAG patients having glaucoma
      surgery or combined glaucoma-cataract surgery. Qualifying preoperative
      intraocular pressure (IOP) was at least 16 mm Hg and historical IOP, at least 21
      mm Hg. The full circumference of the canal was viscodilated and a trabecular
      tensioning suture placed with a microcatheter. Primary outcome measures included
      IOP and glaucoma medication use. RESULTS: At 24 months, all 127 eyes (127
      patients) had a mean IOP of 16.0 mm Hg +/- 4.2 (SD) and mean glaucoma medication
      use of 0.5 +/- 0.8 (baseline values 23.6 +/- 4.8 mm Hg and 1.9 +/- 0.8
      medications). Eyes with canaloplasty alone had a mean IOP of 16.3 +/- 3.7 mm Hg
      and 0.6 +/- 0.8 medications (baseline values 23.2 +/- 4.0 mm Hg and 2.0 +/- 0.8
      medications). Eyes with combined glaucoma-cataract surgery had a mean IOP of 13.4
      +/- 4.0 mm Hg and 0.2 +/- 0.4 medications (baseline values 23.1 +/- 5.5 mm Hg and
      1.7 +/- 1.0 medications). The IOP and medication use results at all time points
      were statistically significant versus baseline (P <.001). The late postoperative
      follow-up identified 3 patients with elevated IOP. No other serious ocular or
      nonocular complications were reported. CONCLUSION: Canaloplasty was safe and
      effective in reducing IOP in adult patients with OAG.

PMID- 19393880
TI  - Optical and visual performance of diffractive intraocular lens implantation after
      myopic laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the optical and visual quality in eyes with diffractive
      intraocular lenses (IOLs) after myopic laser in situ keratomileusis (LASIK).
      SETTING: Fernandez-Vega Ophthalmological Institute, Oviedo, Spain. METHODS: The
      best corrected visual acuity (BCVA [distance]) at 12.5%, 25.0%, and 100%
      contrasts under photopic and mesopic conditions; best distance-corrected near
      acuity; corneal total higher-order aberrations (HOAs); and optical quality by
      modulation transfer function (MTF) were measured after myopic LASIK in eyes with
      a spherical AcrySof ReSTOR SN60D3 IOL or an aspheric Acri.LISA 366D IOL and
      phakic eyes (control). RESULTS: Under photopic conditions at 100% contrast, the
      BCVA was 0.1 logMAR or better in all groups. At 25.0% and 12.5% contrasts, there
      were no statistically significant differences between the aspheric IOL group and
      the spherical IOL or control group (P >.01). The control group had better BCVA
      than the spherical IOL group (P = .0002, 25.0%; P<.0001, 12.5%). Under mesopic
      conditions, the aspheric IOL group had better BCVA than the spherical IOL group
      at all contrasts (P<.01). There was no statistically significant difference
      between the 2 IOL groups in mean best distance-corrected near acuity or between
      all 3 groups in HOAs (P >.01). With 6.0 mm and 3.0 mm pupils, there were no
      statistically significant differences in MTF between the aspheric IOL group and
      the control group; both groups had better MTF than the spherical IOL group with a
      6.0 mm pupil (P<.01). CONCLUSION: After LASIK, the aspheric IOL provided better
      visual quality and optical quality than spherical IOL under mesopic conditions
      (large pupil).

PMID- 19393881
TI  - Femtosecond laser versus mechanical microkeratomes for flap creation in laser in
      situ keratomileusis and effect of postoperative measurement interval on estimated
      femtosecond flap thickness.
AB  - PURPOSE: To prospectively compare laser in situ keratomileusis (LASIK) flaps
      created with a femtosecond laser or a mechanical microkeratome and analyze the
      effect of the postoperative measurement interval on estimated femtosecond flap
      thickness using ultrasound (US) pachymetry. SETTING: Department of Ophthalmology,
      University Hospital of Coimbra, and Coimbra Surgical Centre, Coimbra, Portugal.
      METHODS: Flaps were created with a Hansatome Zero Compression microkeratome
      (Group 1), Zyoptix XP keratome (Group 2), or IntraLase 60 kHz femtosecond laser
      (Groups 3 and 4). Flap thickness was determined by intraoperative US pachymetry
      immediately after flap creation in Groups 1, 2, and 3. In Group 4, pachymetry was
      performed 20 minutes after the laser treatment. The main outcome measures were
      flap thickness and deviation from the target value. RESULTS: Eighty patients had
      LASIK for myopia or myopic astigmatism. The mean flap thickness was 149.1 microm
      +/- 24.9 (SD) in Group 1, 124.7 +/- 23.8 microm in Group 2, 143.1 +/- 18.4 microm
      in Group 3, and 115.5 +/- 12.5 microm in Group 4. The difference in flap
      thickness between Group 3 and Group 4 was statistically significant (P<.01). The
      flap thickness deviation from the target value was 22.8 microm in Group 1, 19.0
      microm in Group 2, 26.1 microm in Group 3, and 10.4 microm in Group 4.
      CONCLUSIONS: Results indicate that the time of measurement after femtosecond
      affects the estimated flap thickness. Waiting 20 minutes after laser treatment
      permitted easier separation and may eliminate the effect of variable corneal
      dehydration on flap measurement by subtraction pachymetry.

PMID- 19393882
TI  - Incidence, management, and visual outcomes of buttonholed laser in situ
      keratomileusis flaps.
AB  - PURPOSE: To describe the incidence, management, and visual outcomes of
      buttonholed laser in situ keratomileusis (LASIK) flaps. SETTING: Private
      practice, Riyadh, Saudi Arabia. METHODS: This retrospective review identified
      eyes that developed buttonholed flaps during LASIK. Preoperative, intraoperative,
      and postoperative data were obtained to identify factors predictive of this
      complication. RESULTS: Of 4250 primary LASIK procedures, 17 eyes (0.4%) with
      buttonholed flaps were identified. Buttonholes occurred with the Hansatome
      microkeratome in 64.7% of eyes and with the Moria microkeratome in 35.3% of eyes,
      the incidence of buttonholed flaps was 0.62% and 0.19%, respectively (P = .03).
      Laser ablation was performed at the same time as buttonhole formation in 8 eyes
      (47.1%) and was aborted in the other eyes. Retreatment was performed in 10 eyes
      (58.8%); of retreated eyes, 6 had repeat LASIK and 3 had surface ablation. The
      final spherical equivalent refraction was -0.38 diopter +/- 0.79 (SD). Two eyes
      had a final loss of more than 2 lines of best corrected visual acuity (BCVA). The
      mean loss of BCVA lines was 0.72 in eyes that had complete LASIK, 0.62 in eyes
      that had aborted LASIK followed by retreatment with repeat LASIK, and 0.80 in
      eyes that had aborted LASIK followed by retreatment with surface ablation.
      CONCLUSIONS: Buttonholed flaps occurred more frequently in the second of 2
      consecutively treated eyes. Microkeratomes that produce a larger diameter flap
      were more likely to produce flap buttonholes. The least loss of BCVA was achieved
      when LASIK was aborted and then repeated after refractive stability.

PMID- 19393883
TI  - Comparison of optical quality metrics to predict subjective quality of vision
      after laser in situ keratomileusis.
AB  - PURPOSE: To compare wavefront-derived metrics to predict subjective quality of
      vision after laser in situ keratomileusis (LASIK) for myopia. SETTING: Department
      of Ophthalmology, Goethe University, Frankfurt am Main, Germany. METHODS: One
      month postoperatively, wavefront sensing was performed and overall subjective
      quality of vision assessed under 3 lighting conditions (photopic, high mesopic,
      low mesopic) with a questionnaire. Four wavefront-error representations were
      computed for a pupil diameter of 6.0 mm and individual physiological pupil
      diameters at 0.4 lux: (1) the visual Strehl ratio based on optical transfer
      function (VSOTF), (2) the root-mean-square (RMS) value of Zernike orders 2 to 5
      (total RMS), (3) higher-order aberration (HOA) RMS, and (4) a wavefront-error
      breakdown into the RMS of lower-order aberrations, coma, spherical aberration,
      and remaining HOA. The impact of the postoperative wavefront error on subjective
      quality of vision was calculated using linear regression analysis. RESULTS: Fifty
      six eyes (29 patients) were included. The ability of wavefront error-derived
      metrics to predict subjective quality of vision was limited. The VSOTF,
      calculated for the best-corrected eye, showed the highest predictability.
      Calculation of wavefront error for individual physiological pupil diameters did
      not improve predictive ability of the metrics. Eyes with a high theoretical
      retinal-image quality had a high subjective quality of vision, and eyes with a
      low subjective quality of vision had a low theoretical image quality.
      CONCLUSIONS: Postoperative wavefront error had limited influence on the
      subjective quality of vision. Postoperative retinal image quality should be kept
      as high as possible to provide good subjective quality of vision.

PMID- 19393884
TI  - Comparison of anterior and posterior elevation map measurements between 2
      Scheimpflug imaging systems.
AB  - PURPOSE: To compare the anterior and posterior elevation measurements above the
      best-fit sphere (BFS) between the Galilei (dual-Scheimpflug) and Pentacam (single
      Scheimpflug) systems in candidates for refractive surgery. SETTING: Poostchi
      Ophthalmology Research Center, Shiraz, Iran. METHODS: In this prospective study,
      both eyes of consecutive patients were examined with the 2 imaging systems. The
      anterior and posterior BFS and the central and maximum elevation measurements in
      each of 4 quadrants were compared between the dual-Scheimpflug system and the
      single-Scheimpflug system. Bland-Altman plots were used to evaluate the agreement
      in the measurements between the imaging systems. RESULTS: The study comprised 31
      patients (62 eyes). The mean radius of the anterior BFS measurement was 7.72 mm
      +/- 0.21 (SD) with the dual-Scheimpflug system and 7.83 +/- 0.21 mm with the
      single-Scheimpflug system. The mean radius of the posterior BFS was 6.37 +/- 0.18
      mm and 6.47 +/- 0.19 mm, respectively. On the anterior and posterior elevation
      maps, the single-Scheimpflug system led to statistically significantly higher
      measurements than the dual-Scheimpflug system in the central, inferior, and
      temporal elevations (P<.001). Bland-Altman plots showed more agreement between
      the systems in anterior elevation measurements than in posterior elevation
      measurements. CONCLUSION: In refractive surgery candidates with healthy eyes, the
      elevation map measurements with the single-Scheimpflug system were significantly
      different from those with the dual-Scheimpflug system in most aspects and
      therefore may lead to misinterpretation of clinical data that could alter
      clinical decisions if the 2 imaging systems are considered interchangeable.

PMID- 19393885
TI  - Management of retained lens fragments after cataract surgery with and without
      pars plana vitrectomy.
AB  - PURPOSE: To compare the clinical course of patients with retained lens particles
      after phacoemulsification who had early or late pars plana vitrectomy (PPV) and
      removal of retained lens fragments or who were managed medically. SETTINGS:
      Private practice and University of Louisville, School of Medicine, Louisville,
      Kentucky, USA. METHODS: This retrospective review comprised patients who had
      cataract fragments dislocated into the vitreous during attempted cataract
      extraction and intraocular lens implantation over an 8-year period. Patients were
      divided into 3 groups. The early surgery group was treated with PPV and removal
      of lens fragments within 1 week of cataract surgery. The late surgery group had
      PPV more than 2 weeks after cataract surgery. The medical therapy group was
      managed with topical and systemic medications alone. The visual acuity, degree of
      corneal edema, inflammation, and intraocular pressure (IOP) were measured.
      Postoperative follow-up was at 7, 14, and 30 days and 1 year. RESULTS: The study
      evaluated 42 patients (12 early surgery, 15 late surgery, and 15 medical
      therapy). Demographic characteristics, visual acuity, and mean IOP values at
      presentation were similar between the 3 groups. Visual acuity was not
      statistically significantly different between groups at 30 days and 1 year. There
      was no statistically significant difference in IOP between groups throughout the
      study period. CONCLUSIONS: Retained lens fragments were managed conservatively
      with good visual results. Vitrectomy was effective in patients with retained lens
      fragments not responding to topical and oral medication. Results indicate that
      surgery can be successfully delayed in certain patients.

PMID- 19393886
TI  - Morphologic changes in the anterior segment after phacovitrectomy for
      proliferative diabetic retinopathy.
AB  - PURPOSE: To determine whether combined phacoemulsification and intraocular lens
      implantation with pars plana vitrectomy (PPV) (phacovitrectomy) in patients with
      proliferative diabetic retinopathy (PDR) causes morphologic changes in the
      anterior segment and to evaluate whether there is a relationship between the
      anatomic changes and inflammatory complications. SETTING: Department of
      Ophthalmology, Chonnam National University Hospital, Gwangju, South Korea.
      METHODS: Patients who had uneventful surgery for PDR were divided into 2 groups
      (phacovitrectomy and PPV only). Morphologic changes in the ciliary regions were
      measured by ultrasound biomicroscopy (UBM) 1 day before surgery and 1, 2, 3, 5
      days, 2 weeks, 1 and 2 months after surgery. The UBM parameters and inflammatory
      complications in the 2 groups were compared. RESULTS: The study comprised 60
      patients; 30 had phacovitrectomy and 30, PPV only. The frequency of supraciliary
      effusions was higher in the phacovitrectomy group (24/30, 80%) than in the PPV
      only group (14/30, 46%) (P = .015). The decrease in angle opening and anterior
      chamber depth was more prominent after phacovitrectomy. The incidence of
      complications was higher in the phacovitrectomy group than in the PPV-only group
      (60% versus 30%, abnormal intraocular pressure; 30% versus 7%, intraocular fibrin
      and posterior synechia formation); the complications were associated with
      supraciliary effusions. CONCLUSIONS: The results indicate that phacovitrectomy
      for PDR may induce more morphologic changes in the anterior segment. Supraciliary
      effusions were associated with inflammatory complications. Appropriate control of
      postsurgical inflammation is necessary in phacovitrectomy for PDR.

PMID- 19393887
TI  - Microcoaxial cataract surgery outcomes: comparison of 1.8 mm system and 2.2 mm
      system.
AB  - PURPOSE: To compare clinical outcomes of a 1.8 mm and a 2.2 mm microcoaxial
      cataract surgery system. SETTING: Department of Ophthalmology and Visual Science,
      Kangnam St. Mary's Hospital, College of Medicine, Catholic University of Korea,
      Seoul, Korea. METHODS: In a prospective study, eyes were randomly selected to
      have phacoemulsification using a Stellaris system or an Intrepid Infiniti system.
      The initial incision size was 1.8 mm and 2.2 mm, respectively. Measured
      intraoperative parameters included phacoemulsification time, mean cumulative
      dissipated ultrasound energy (CDE), change in incision size at each step of
      surgery, and total volume of balanced salt solution (BSS) used. The best
      corrected visual acuity (BCVA), corneal astigmatism, corneal thickness, and
      endothelial cell count were evaluated preoperatively and postoperatively.
      RESULTS: The study evaluated 86 eyes of 78 patients (43 eyes in each group).
      There were no significant differences in postoperative BCVA, surgically induced
      astigmatism, or amount of BSS used between the 2 systems (P >.05). However, for
      high-density cataracts, the 1.8 mm group had a greater change between the initial
      incision size and the incision size after phacoemulsification (P = .019, nuclear
      opalescence [NO] NO3; P = .001, NO4), a longer phacoemulsification time (P =
      .013, NO3), greater mean CDE (P = .005, NO3; P = .001, NO4), and greater corneal
      endothelial cell loss (P = .003, NO4). CONCLUSIONS: Both systems were safe and
      effective in microcoaxial phacoemulsification. The 1.8 mm system performed better
      with cortical-type cataract and the 2.2 mm system, with high-density nuclear-type
      cataract.

PMID- 19393888
TI  - Ultrasound biomicroscopy comparison of ab interno and ab externo scleral fixation
      of posterior chamber intraocular lenses.
AB  - PURPOSE: To compare ab interno and ab externo scleral fixation of posterior
      chamber intraocular lenses (PC IOLs) using ultrasound biomicroscopy (UBM) to
      determine the centration of IOL optic and the position of the haptics in relation
      to the sulcus. SETTING: Kasr Eleini Hospital, Cairo University, Cairo, Egypt.
      METHODS: Consecutive patients with aphakia had ab externo or ab interno scleral
      fixation of a PC IOL. Ultrasound biomicroscopy was used preoperatively to
      determine whether the eyes were unsuitable for capsule fixation and 3 and 6
      months postoperatively, determine the position of the haptics in relation to the
      ciliary sulcus, and evaluate centration of the optic. RESULTS: Fifteen eyes of 14
      patients were studied. Eight patients had ab externo fixation, and 7 had ab
      interno fixation. The haptics were located in the sulcus in 31% of cases with ab
      externo fixation and 29% with ab interno fixation. The difference was not
      statistically significant. CONCLUSION: Ab interno and ab externo scleral
      fixation, which are both blind procedures, resulted in comparable low rates of
      sulcus fixation.

PMID- 19393889
TI  - Visual function after implantation of an aspheric bifocal intraocular lens.
AB  - PURPOSE: To evaluate distance, intermediate, and near vision after bifocal
      aspheric AcrySof ReSTOR SN6AD1 intraocular lens (IOL) implantation. SETTING:
      Fernandez-Vega Ophthalmological Institute, Oviedo, Spain. METHODS: Binocular
      distance best corrected visual acuity (BCVA) (4.0 m), best distance-corrected
      near (40.0 cm) and intermediate (70.0, 60.0, 50.0 cm) acuities, and contrast
      sensitivity under photopic (85.0 candelas [cd]/m(2)) and mesopic (3.0 cd/m(2))
      conditions with and without glare were measured postoperatively. A patient
      satisfaction and visual phenomena questionnaire was administered. RESULTS: Six
      months postoperatively, the mean acuities (logMAR) were binocular BCVA, -0.064 +/
      0.049 (SD); best corrected near, -0.041 +/- 0.061; best corrected intermediate,
      0.147 +/- 0.130 (70.0 cm), 0.036 +/- 0.133 (60.0 cm), and -0.126 +/- 0.077 (50.0
      cm). The BCVA and best corrected near acuity were 20/25 or better in all
      patients. Through-focus binocular logMAR acuities had 2 peaks at the expected far
      focus and near focus (0.00 diopter [D] and -2.40 D, respectively), with somewhat
      reduced acuity (20/32) at intermediate distances. Photopic contrast sensitivity
      was within the standard normal range. Mesopic contrast sensitivity was lower than
      under photopic conditions, particularly at higher spatial frequencies. Patients
      reported good performance for distance, near, and intermediate visual tasks with
      no or minimal difficulty with specific tasks. No patient reported severe visual
      phenomena; halos and glare were rated as none to moderate. CONCLUSIONS: The
      aspheric IOL provided good functional vision at far and near, with lower
      performance at intermediate distance; good photopic contrast sensitivity and
      lower mesopic performance; and a low incidence of visual disturbances.

PMID- 19393890
TI  - Corneal crosslinking: riboflavin concentration in corneal stroma exposed with and
      without epithelium.
AB  - PURPOSE: To evaluate intrastromal concentrations of riboflavin with and without
      epithelium to ensure the efficacy and safety of corneal crosslinking (CXL) by the
      standard and transepithelial procedures. SETTING: Department of Ophthalmology and
      Department of Pharmacology G. Segre, Siena University, Siena, Italy. METHODS:
      This study comprised keratoconic patients enrolled for penetrating keratoplasty
      (PKP) and warm-stored sclerocorneal rings unsuitable for transplantation. Half
      the PKP specimens were debrided, and half were left with the epithelium in situ.
      One of the latter and 1 debrided sample were not exposed to riboflavin
      (controls). Samples in both groups were soaked with 0.1% riboflavin-dextran 20%
      solution instilled every 2 minutes for 5, 15, and 30 minutes. Riboflavin
      concentrations were determined by high-performance liquid chromatography (HPLC).
      RESULTS: The study evaluated 14 PKP specimens and 16 sclerocorneal rings. Control
      samples did not show a riboflavin emission peak. In exposed samples with
      epithelium, the mean riboflavin concentration was 91.88 ng/g after 5 minutes of
      exposure, 95.60 ng/g after 15 minutes, and 94.92 ng/g after 30 minutes. In the
      debrided samples, the mean riboflavin concentration was 14.42 microg/g, 20.92
      microg/g, and 24.06 microg/g, respectively. No differences were seen between the
      in vivo samples and the ex vivo samples. CONCLUSIONS: The HPLC quantitative study
      showed that stromal concentrations of riboflavin increased with exposure time
      only if the epithelium was removed. A theoretically safe and effective riboflavin
      concentration of 15 microg/g was obtained for ultraviolet A-induced CXL only
      after the epithelium was removed and after at least 10 minutes of riboflavin
      application every 2 minutes.

PMID- 19393891
TI  - Alkylphosphocholines as a potential pharmacologic prophylaxis for posterior
      capsule opacification.
AB  - PURPOSE: To evaluate the effect of alkylphosphocholines (APCs) on human lens
      epithelial cell (LEC) proliferation, attachment, and migration in a well
      established in vitro model. SETTING: Department of Ophthalmology, Ludwig
      Maximilians-University, Munich, Germany. METHODS: The immortalized human LEC line
      HLE-B3 was incubated for 24 hours with APC in different concentrations in the
      presence of Eagle's modified essential medium supplemented with fetal calf serum
      under standard cell-culture conditions. The trypan blue exclusion test and live
      dead assay were performed to exclude toxic concentrations. To determine cell
      proliferation, cells were incubated with APCs at the maximum slope of the growth
      curve for 24 hours before the tetrazolium dye-reduction assay (MTT test) was
      performed. After cells were seeded on coated 24-well plates, incubated with APCs,
      and rinsed with phosphate-buffered saline, cell attachment was assessed by the
      MTT test. Migration was determined by a modified Boyden chamber method after
      incubation of LECs with APCs. RESULTS: Alkylphosphocholines were effective
      inhibitors of human LEC proliferation, attachment, and migration at nontoxic
      concentrations in vitro. The 50% inhibitory concentration was close to 0.1 mM. An
      APC concentration of 1.0 mM accounted for the following: inhibition of cell
      proliferation of more than 80%, reduction in cell attachment to 66.5%, and
      inhibition of cell migration of more than 90%. All effects were dose dependent.
      No toxic effects were detected compared with controls. CONCLUSIONS:
      Alkylphosphocholines might have the potential for topical application as a single
      dose agent to prevent posterior capsule opacification formation. However, further
      studies are needed before a clinical application can be considered.

PMID- 19393892
TI  - Intraocular lens calculation in extreme myopia.
AB  - PURPOSE: To study from a theoretical viewpoint the effects in cases of extreme
      myopia of the different axial length (AL) behavior of current intraocular lens
      (IOL) calculation formulas and the problems caused by changes in lens geometry in
      the transition from plus to minus lenses. SETTING: University Eye Hospital,
      Wuerzburg, Germany. METHODS: A comparison of the thick-lens and thin-lens
      approach was made with allowance for the role of IOL constants and exemplified in
      model calculations based on design data of the MA60MA IOL in the power range from
      +5.0 to -5.0 diopters. Ray tracing was used to define model eyes for the MA60MA
      IOL, and the IOL constants producing the correct lens powers with the Haigis
      formula were determined. RESULTS: An equation was derived linking lens geometry
      represented by the positions of the principal planes with the effective thin-lens
      position and thus with the respective IOL constants. Because IOL geometry changes
      considerably at the transition from plus to minus powers, a corresponding change
      is obtained in the necessary IOL constants. If no allowance is made for this
      effect, refractive errors increasing with AL will be associated with minus-power
      IOLs. CONCLUSION: Plus IOLs and minus IOLs have to be characterized by different
      sets of IOL constants.

PMID- 19393893
TI  - Cataract wound closure with a polymerizing liquid hydrogel ocular bandage.
AB  - PURPOSE: To determine whether a polymerizing liquid hydrogel ocular bandage can
      create a watertight seal in a clear corneal cataract incision. SETTING:
      Laboratory. METHODS: Twenty-four clear corneal cataract wounds were made in eye
      bank corneas. Twelve wounds were treated with a tissue-adherent hydrogel ocular
      bandage; 12 control wounds received no bandage. Each eye was tested under low
      pressure conditions to detect fluid ingress of India ink on the eye's surface.
      Eyes were tested again with external compression to distort the wound to detect
      fluid egress. RESULTS: India ink did not enter the wound in any incision in the
      treated group but did enter 9 (75%) of 12 incisions in the control group. Fluid
      egress with external manipulation did not occur in any treated eyes but did occur
      in 11 (92%) control eyes. CONCLUSION: A tissue-adherent hydrogel ocular bandage
      created a watertight seal in clear corneal cataract wounds.

PMID- 19393894
TI  - Comparison of actual vacuum pressures at the end of 3 phacoemulsification tips in
      swine eyes.
AB  - PURPOSE: To compare the actual vacuum pressure at the end of an aspiration bypass
      system (ABS) phaco tip and a conventional tip in conditions similar to those
      during human cataract surgery. SETTING: Kangbuk Samsung Hospital, Seoul, Korea.
      METHODS: A 4.0 mm diameter rubber eraser ball was inserted in a phacoemulsified
      swine eye and engaged to a phaco tip. With a vacuum pressure of 300 mm Hg, the
      eraser ball was pulled in the opposite direction with the phaco tip. The pulling
      power separating the eraser ball from the phaco tip was measured using the volume
      of water dripped into a container connected to the eraser ball. Measurements were
      taken with an Infiniti ABS tip and 2 conventional tips: Sovereign (conventional
      tip S) and Infiniti (conventional tip I). Measurements were taken alternatively
      at random in the same eye. RESULTS: The mean pulling power was 17.35 mL +/- 5.01
      (SD) with conventional tip S and 16.85 +/- 4.45 mL with conventional tip I. The
      mean pulling power of the ABS tip was 13.35 +/- 4.32 mL, which was a mean 20.8%
      lower than that of conventional tip I (P = .016) and 23.1% lower than that of
      conventional tip S (P = .010). CONCLUSIONS: The actual vacuum pressure of the
      phaco tip was significantly influenced by the presence of the ABS hole. To
      compensate for the decrease in actual vacuum pressure, surgeons should be aware
      of the characteristics of the ABS tip being used and change the standard settings
      accordingly.

PMID- 19393895
TI  - Outcomes of laser refractive surgery for myopia.
AB  - Many advances have been made in laser refractive surgery, and this review
      examines how they have affected treatment outcomes in individuals with varying
      degrees of myopia (law, moderate, and high). Studies with a minimum follow-up of
      1 year with at least 2 of the 3 major outcome measures--efficacy, stability, and
      safety--were reviewed, and how the findings were affected by differences in
      ethnicity was assessed.

PMID- 19393896
TI  - Transscleral fixation of a toric intraocular lens to correct aphakic keratoplasty
      with high astigmatism.
AB  - A 71-year-old man with penetrating keratoplasty (PKP) and aphakia in the right
      eye and a preoperative refraction of +20.0 -11.0 x 38 and logMAR visual acuity of
      20/60 presented to our hospital. The capsular support was absent because of
      previous complicated intracapsular cataract extraction. The implanted IOL was a
      custom-made Rayner 570T with +20.5 diopters (D) sphere and +11.0 D cylinder. The
      IOL's special haptics allowed it to be safely fixated in the sagittal plane. The
      postoperative refraction was +1.0 -2.0 x 5 with logMAR acuity of 20/60. Follow-up
      of 2 years revealed no IOL decentration. Transscleral fixation of a toric IOL
      requires exact outlining. Our case shows that this is possible and can result in
      improved visual rehabilitation.

PMID- 19393897
TI  - Suture-related corneal infections after clear corneal cataract surgery.
AB  - Three patients at our institution developed corneal infections associated with
      sutures placed after clear corneal incision cataract surgery. The time to
      infection was 9 weeks, 22 months, and 33 months. One patient required injection
      of intravitreal antibiotic agents for presumed endophthalmitis associated with
      the corneal infection. Two patients were treated with topical fortified
      antibiotic eyedrops only. Although there was no significant change in visual
      acuity after resolution of the infection, morbidity from suture-related corneal
      infections can be significant. Routine suture removal in the early postoperative
      period may be warranted to prevent such infections.

PMID- 19393898
TI  - Rupture of anterior lens capsule from blunt ocular injury.
AB  - We report 3 cases of blunt trauma causing rupture of the anterior lens capsule
      with cataract formation. The injuries were caused by a paintball gun, a ball
      bearing air pistol, and an aluminum rivet. In all 3 cases, the anterior capsule
      tears were central and the posterior capsules and zonules intact; uneventful
      cataract extraction with implantation of an intraocular lens was performed. The
      postoperative visual acuities was 20/40 in 1 case and 20/20 in the other 2 cases.
      We propose that the anterior lens capsule may have been torn by direct contusion
      from rapid focal indentation of the cornea onto the lens (coup injury) or by a
      fluid-mechanical, anteriorly directed rebound of the vitreous, bursting open the
      anterior capsule (contrecoup injury).

PMID- 19393899
TI  - Reactivated herpetic keratitis following laser in situ keratomileusis.
AB  - A 40-year-old woman presented with an unusual form of corneal herpetic
      reactivation 5 weeks after laser in situ keratomileusis. The cornea showed
      diffuse edema and a stromal ring infiltrate (disciform in appearance). Oral
      antiviral and topical steroids in tapered dosages were administered. The
      infiltrate disappeared within 6 weeks. Progressive improvement was also seen in
      all the parameters on Pentacam scans, including the pachymetry, keratometry
      readings, and elevation on the anterior float. Herpetic reactivation may occur in
      many forms after excimer laser ablation. Timely diagnosis and management is
      crucial to maintain good structural and visual outcomes. Pentacam analysis may
      serve as a useful adjunct in following the progression of herpetic reactivation
      cases.

PMID- 19393900
TI  - Effect of partial and full correction of corneal spherical aberration on visual
      acuity and contrast sensitivity.
AB  - A 60-year-old white man had cataract surgery with an AcrySof IQ intraocular lens
      (IOL) implanted in the right eye and a Tecnis IOL implanted in the left eye. The
      ocular spherical aberration (SA) target for a 6.0 mm pupil was +0.10 microm for
      the right eye and 0 microm for the left eye. After surgery, the ocular SA in the
      right eye was significantly higher than that in the left eye (+0.112 microm +/-
      0.002 [SD] versus +0.021 +/- 0.003 microm; P<.001). No between-eye difference in
      the best corrected visual acuity and photopic contrast sensitivity was found. The
      contrast sensitivity was significantly better in the eye with the AcrySof IQ IOL
      at 12 and 18 cpd under mesopic conditions. The best contrast sensitivity was
      achieved in the eye with a residual ocular SA of about +0.10 microm.

PMID- 19393901
TI  - Intraocular pressure after phacoemulsification in eyes with pseudoexfoliation.

PMID- 19393902
TI  - Partial coherence interferometry in a teaching hospital.

PMID- 19393903
TI  - The increasing body of research data in clinical medicine has led to the need for
      evidence synthesis studies. Preface.

PMID- 19393904
TI  - Systematic reviews and meta-analyses in infectious diseases: how are they done
      and what are their strengths and limitations?
AB  - In infectious diseases, as in other domains, systematic reviews and meta-analyses
      are the type of research most easily translated into clinical practice.
      Practitioners should familiarize themselves with the methodology of systematic
      reviews and meta-analyses, their interpretation, and their limitations.

PMID- 19393905
TI  - Statistical considerations in meta-analysis.
AB  - Systematic reviews and meta-analyses have recently emerged as key sources of
      evidence to inform clinical care, from bedside individualized decisions to policy
      making. This article discusses the principles behind statistical methods for
      quantitative evidence synthesis, including meta-analysis and meta-regression. The
      authors present pertinent concepts in an intuitive and nonmathematical fashion by
      use of examples from the infectious diseases literature.

PMID- 19393906
TI  - Identifying risk factors for infections: the role of meta-analyses.
AB  - Systematic review and meta-analysis are assuming greater importance in
      influencing policy makers and clinical opinion worldwide. Many discussions and
      publications have considered the merits of meta-analysis of epidemiologic data.50
      Some observers suggest that meta-analysis of observational studies should be
      abandoned altogether. 51 In the authors' opinion, statistical combination of
      observational studies should not be a primary goal of a review. Analysis of
      heterogeneity between longitudinal studies, however, would provide more insights
      than mathematical calculation of the summary risk. Meta-analyses of risk factors
      for infections should strictly follow guidelines for meta-analyses of
      observational studies. A study protocol should be written in advance, completed
      literature searches performed, and studies selected in a reproducible and
      objective fashion. Biologic plausibility must be addressed. The reported findings
      should be interpreted with caution, taking into account the limitations of
      various methodologic aspects of risk factors studies. An important role for meta
      analyses in this field would be to clarify hypotheses to be formulated for future
      Identifying Risk Factors for Infections 221 studies and stress limitations
      strictly related to studies on risk factors for bacterial and viral infections.

PMID- 19393907
TI  - An overview of meta-analyses of diagnostic tests in infectious diseases.
AB  - This review summarizes meta-analyses evaluating the accuracy of diagnostic tests
      for infectious diseases. Systematic searches identified 55 meta-analyses that
      satisfied inclusion criteria of reporting diagnostic accuracy of an index test
      compared with a reference test. All reviews were assessed for methods and
      reporting. The overall assessment underlined problems in several key steps:
      reporting detailed information from primary studies about the study design and
      patient characteristics, reference and index tests characteristics, and review
      methods. The execution and reporting of systematic reviews of diagnostic tests
      need to be improved.

PMID- 19393908
TI  - Meta-analyses on the optimization of the duration of antimicrobial treatment for
      various infections.
AB  - A mainstay of antibiotic treatment is its optimal duration for the management of
      infections. Many randomized control trials have been conducted on these issues
      during the last years. The results from these randomized control trials have been
      analyzed by various meta-analyses. To address the role of meta-analyses that
      compared a short-duration with a long-duration of the same antibiotic treatment
      for various infections a search was made in PubMed, Scopus, and Cochrane
      databases for relevant meta-analyses.

PMID- 19393909
TI  - Combination antimicrobial treatment versus monotherapy: the contribution of meta
      analyses.
AB  - Systematic reviews and meta-analyses have put into perspective the clinical
      implications of in vitro synergy (Box 1). Randomized, controlled trials are the
      cornerstone of evidence-based medicine. The trials included in the meta-analyses
      described in this article are the building blocks of evidence. Individual trials,
      however, were individually underpowered to address the broader clinical question
      and relevant patient-related outcomes. On the question of combination therapy,
      meta-analyses have shaped the complete picture. The interactions observed in
      vitro have not been shown to improve patient-related outcomes. Authors of
      systematic reviews have the privilege of considering and selecting the clinical
      outcomes most relevant for the individual patient. Thus, all-cause mortality,
      rather than treatment failure with antibiotic modifications or infection-related
      mortality, has been selected for the assessment of patients who had severe gram
      negative infections and febrile neutropenia. Mortality and relapse were assessed
      for patients who had endocarditis, and clinical and lung function scores were
      assessed for patients who had cystic fibrosis. The authors hope that the
      dissemination of these reviews will lead clinicians and researchers to consider
      primarily these outcomes when appraising or designing clinical research. These
      are the outcomes that clinicians target when treating the patient. Systematic
      reviews have the virtue of a broad, systematic, and explicit search. In some
      areas, such as the use of combination therapy to treat gram-positive infections
      in general, and specifically to treat endocarditis and Pseudomonas aeruginosa
      bacteremia, the main contribution of the reviews was to show that current
      practice is based on very limited clinical evidence. This finding does not refute
      current practice but should serve to guide future trials and opens the
      possibility for a different choice of therapy when standard guidelines are
      difficult to implement. The fact that to date no evidence has been accrued for
      these infections is not surprising. The clinical question of combination therapy
      is of no major interest to pharmaceutical companies sponsoring most trials; the
      infections are rare; and the study design is complex. This gap in knowledge calls
      for a new trial paradigm: collaborative investigator-initiated, multicenter
      trials. When randomized, controlled trials are unfeasible, the use of novel
      methods for adjustments in observational studies, such as propensity analyses
      using large databases, might approximate the true effect of combination therapy
      in a wider patient population.

PMID- 19393910
TI  - Meta-analytical studies on the epidemiology, prevention, and treatment of human
      immunodeficiency virus infection.
AB  - Since the beginning of the epidemic, extensive research has been conducted in the
      field of HIV infection. Original research and subsequent meta-analyses have
      contributed to a better understanding of the disease. Epidemiologic research has
      shown, for example, that male circumcision reduces the risk of female-to-male
      transmission. Nevertheless, the question whether circumcision confers protection
      against HIV transmission in MSM remains open. Studies have shown a positive
      correlation between HIV and HSV-2 infection. However, a recent RCT found that
      suppressive antiherpes therapy did not affect rates of HIV acquisition. Meta
      analytical studies have advanced the knowledge on the global prevalence of
      infection among MSM, and disparities among black and white MSM. They have also
      solidified the evidence that the prophylactic use of ARVs reduces the risk of
      MTCT. It has also been shown that prolonged ruptured of membranes increases the
      rates of vertical transmission, and that breastfeeding is associated with
      postnatal transmission. In addition, prognostic markers of disease progression
      have been identified. The introduction of ART has resulted in substantial
      improvements in morbidity and mortality for HIV-seropositive individuals. Several
      studies have defined recommended and alternative regimens. In a recent meta
      analysis it was shown that in treatment naive patients, NNRTI-based or boosted-PI
      based regimens are superior to triple NRTI or unboosted PI-based regimens in
      terms of virologic suppression. Recent evidence has demonstrated that ART can be
      successfully used in Africa with better outcomes in those receiving free
      treatment. Regarding resistance testing in treatment-experienced patients with
      virologic failure, GRT offers a benefit of small magnitude and there is
      insufficient evidence to support the use of PRT, in contrast to current
      guidelines. Meta-analyses have also shown that interventions to improve adherence
      can be successfully implemented. Finally, the efficacy of the influenza and
      hepatitis vaccine in the setting of HIV infection has been analyzed. As our
      knowledge advances, further questions will inevitably arise and will need to be
      addressed in well-conducted trials.

PMID- 19393911
TI  - Meta-analyses on behavioral interventions to reduce the risk of transmission of
      HIV.
AB  - Different behavioral interventions have found to be efficacious in reducing high
      risk sexual activity. Interventions have been evaluated in both original research
      and meta-analytic reviews. Most of the studies have shown that interventions are
      efficacious among different study populations. In adolescents, both in- and out
      of-the classroom interventions showed a decrease in the risk of unprotected sex.
      In African Americans, greater efficacy was found for interventions including peer
      education. For Latinos, effect was larger in interventions with segmentation in
      the same gender. Geographic and social isolation are barriers in approaching MSM.
      For IDUs, interventions provided within a treatment program have an impact on
      risk reduction above that produced by drug treatment alone. Finally, people
      diagnosed with HIV tend to reduce their sexual risk behavior. However, adherence
      to safe sex practices for life can be challenging. Relentless efforts for
      implementation of behavioral interventions to decrease high-risk behavior are
      necessary to decrease HIV transmission.

PMID- 19393912
TI  - Meta-analyses on viral hepatitis.
AB  - This article summarizes the meta-analyses of interventions for viral hepatitis A,
      B, and C. Some of the interventions assessed are described in small trials with
      unclear bias control. Other interventions are supported by large, high-quality
      trials. Although attempts have been made to adjust for unclear bias control,
      analysis of publication bias and other biases is difficult when only few trials
      are available. It is possible that some of the meta-analyses presented in this
      article are biased. Furthermore, performing updated cumulative meta-analyses also
      may introduce random error.3,4 The extent and direction of bias may vary. On
      average, however, bias leads to overestimated intervention benefits.1
      Accordingly, the benefit of some of the interventions suggested in this article
      may be exaggerated by systematic and random errors. Additional research including
      large, randomized trials is necessary to clarify the true intervention effects.

PMID- 19393913
TI  - Meta-analyses on the prevention and treatment of respiratory tract infections.
AB  - The authors have endeavored to provide an overview of meta-analyses on the
      prevention and treatment of RTIs. Meta-analyses are useful tools to address
      clinically relevant questions; however, their inherent limitations should be
      taken into consideration when interpreting their findings.

PMID- 19393914
TI  - Meta-analyses in prevention and treatment of urinary tract infections.
AB  - Urinary tract infections (UTI) are common, and complications result in
      significant morbidity and mortality and also consume resources. This overview
      summarizes the current evidence for the prevention and treatment of UTI in adults
      and children from meta-analyses. The quality and applicability of this evidence
      in clinical practice for different patient groups is discussed. Suggestions are
      made for future research, because it is apparent that there are evidence gaps for
      particular subgroups of people.

PMID- 19393915
TI  - Systematic reviews in malaria: global policies need global reviews.
AB  - This article highlights systematic reviews of malaria research and what has been
      learned about applying methods of research synthesis in this particular
      infectious disease over the last 15 years. It illustrates how systematic reviews
      have been used to guide policy, shows what has been learned about synthesizing
      research in this area, and reflects on how best to maximize their uptake in
      policy and practice.

PMID- 19393916
TI  - Meta-analysis on surgical infections.
AB  - Meta-analysis on surgical infections may be a useful tool that can provide more
      accurate outcome estimates than other conventional types of studies. Published
      meta-analyses in surgical infections tend to focus mainly on the use of
      antimicrobial prophylaxis and on the comparison of different procedures or
      techniques for the treatment of surgical infections. The majority concern
      surgical infections in abdominal surgery. However, mortality is reported as
      primary outcome in few meta-analyses. Meta-analyses focusing exclusively on
      surgical infections, reporting data on mortality as a primary outcome, and
      comparing different antibiotic regimens for the treatment of surgical infections
      should be conducted.

PMID- 19393917
TI  - Meta-analyses on pediatric infections and vaccines.
AB  - In pediatric infections, meta-analyses have helped clarify several controversial
      management issues. Unfortunately, many more aspects remain to be elucidated. This
      is particularly true in the field of UTIs, the most common serious bacterial
      infections in children, where prospective, well-designed, randomized clinical
      trials are urgently needed. Regarding vaccines, it is generally acknowledged
      that, although meta-analyses can provide useful information on their value,
      people who make decisions and set policies should not rely on that information
      alone, but rather use it alongside other sources of information. The fact that
      government policies do not always coincide with conclusions produced by meta
      analyses in the field of vaccinations should not be regarded as a failure of the
      statistical methodology, but rather as a result of the complex societal and
      financial (cost versus benefit) decisions.

PMID- 19393918
TI  - Determinants of plasma adiponectin levels in nondiabetic subjects with moderate
      to severe chronic kidney disease.
AB  - OBJECTIVE: Our objective was to determine factors associated with adiponectin
      levels in subjects with stage III to IV chronic kidney disease (CKD). DESIGN: We
      used a cross-sectional analysis. SETTING: All kidney-disease subjects and
      controls were recruited at Vanderbilt University Medical Center (Nashville, TN)
      and Maine Medical Center (Portland, ME). PATIENTS: We recruited 95 stage III to
      IV CKD subjects. Kidney-disease subjects with history of diabetes mellitus were
      excluded from the study. INTERVENTIONS: There were no interventions. RESULTS:
      Subjects with stage IV CKD had significantly higher adiponectin levels compared
      with those with stage III CKD (30.6 +/- 22.8 microg/mL vs. 21.1 +/- 14.6
      microg/mL mean +/- SD, P = .05). Adiponectin was significantly correlated with
      gender (P = .01), high-density lipoproteins (P < .001), triglycerides (P = .004),
      and weight (P = .04) upon unadjusted analysis. Using multiple linear regression
      analysis, gender (P = .03), high-density lipoproteins (P = .001), triglycerides
      (P = .04), and high-sensitivity C-reactive protein (P = .004) were independently
      associated with adiponectin. CONCLUSIONS: Gender, high-density lipoproteins,
      triglycerides, and high-sensitivity C-reactive protein are major determinants of
      adiponectin levels in nondiabetic stage III to IV CKD. Insulin resistance, body
      mass index, and body fat percentage were not associated with adiponectin levels.
      Plasma adiponectin levels are difficult to interpret in the setting of CKD
      because of multiple confounders that may influence the relationship between
      adiponectin, adiposity, and insulin resistance.

PMID- 19393919
TI  - Usefulness of nutrition facts label for persons with chronic kidney disease.
AB  - OBJECTIVE: We sought to determine what information should be included on the
      nutrition facts label (NFL) to improve its usefulness for individuals with
      chronic kidney disease (CKD). DESIGN: Our survey asked for frequency of food
      label reading, use of information on the label related to specific nutrients, and
      perceived needs. SETTING: Our survey was internet-based. SUBJECTS: Our subjects
      included 317 individuals with CKD and caregivers who self-subscribed to
      electronic mailing lists maintained by nationally based groups providing
      education and/or support for individuals with CKD. INTERVENTION: The intervention
      consisted of an analysis of survey results. MAIN OUTCOME MEASURES: Main outcome
      measures included respondent self-reported behaviors, opinions, attitudes,
      knowledge, and perceived needs related to the NFL in terms of foods and
      beverages. RESULTS: Survey respondents (81.8%) rated nutrition as important
      (39.2%) or very important (42.6%) when making food choices. A roughly equal
      number (82.6%) indicated reading the NFL often for the amounts of nutrients in a
      food. However, less than one fourth of the respondents (24.0%) were able to
      determine the amount of calcium in a food correctly, based on percent daily value
      (%DV), and many (64.6%) indicated they did not know how to convert the %DV to an
      absolute amount (the 100% daily value for calcium is 1000 mg). Respondents
      indicated that they decided not to purchase foods that did not list absolute
      amounts of nutrients of concern (58.4% for potassium, and 53.9% for phosphorus)
      on the NFL. CONCLUSIONS: Individuals with CKD would prefer, or find it more
      useful, to see nutrients of concern listed in absolute amounts on the NFL. They
      also indicated that potassium and phosphorus should be required on the label, to
      allow the option of determining whether to include a food in their diet.

PMID- 19393921
TI  - Proximal radio-ulnar synostosis and nonunion after olecranon fracture tension
      band wiring: a case report.

PMID- 19393922
TI  - Challenging the conclusion, "Clinical outcome was essentially not affected by the
      notch".

PMID- 19393924
TI  - Regarding "Open intercondylar fractures of the distal humerus: management using a
      mini-external fixator construct".

PMID- 19393926
TI  - Editor's note.

PMID- 19393927
TI  - Charles Neer: on the giant of the shoulder.
AB  - In the world of orthopedics, certain giants have become known as associated with
      a single subspecialty or for work on a single joint. Among these are John
      Charnley, for his work on total hip arthroplasty, and Amory Codman, for his work
      on the shoulder. But in the second half of the 20th century, the true giant of
      shoulder surgery was Charles Neer. His contributions to our subspecialty may not
      have been surpassed by any orthopedic surgeon for any subspecialty. This article
      explores his life and his contributions to shoulder surgery from those who knew
      him best.

PMID- 19393928
TI  - Manipulation or intra-articular steroids in the management of adhesive capsulitis
      of the shoulder? A prospective randomized trial.
AB  - BACKGROUND: The management of adhesive capsulitis (frozen shoulder) is
      controversial. The authors present a prospective randomized study comparing the
      outcome, at a two-year follow-up period, of two groups of patients treated either
      by manipulation of the shoulder under anaesthetic or by intra-articular shoulder
      injections using steroid with distension. METHODS: Fifty-three patients suffering
      from Idiopathic "Primary" Frozen Shoulder were prospectively randomized into two
      treatment groups and followed up for two years from the start of treatment.
      Patients were assessed using the Constant score, a Visual Analogue Score, and the
      SF36 questionnaire. RESULTS: No statistical differences were found between the
      two groups of patients with regards to the outcome measures. CONCLUSION:
      Treatment using steroid injections with distension as an out-patient is therefore
      recommended for the treatment of Idiopathic "Primary" Frozen Shoulder. This has
      the same clinical outcome as a manipulation under anaesthetic with less attendant
      risks.

PMID- 19393929
TI  - Biomechanical evaluation of different designs of glenospheres in the SMR reverse
      total shoulder prosthesis: range of motion and risk of scapular notching.
AB  - BACKGROUND: Reverse total shoulder arthroplasty is a treatment option for cuff
      tear arthropathy. Scapular notching remains a concern. This biomechanical study
      compared the range-of-motion in different designs of glenospheres and hence the
      relative risk of scapular notching. METHOD: A precision coordinate device was
      used to investigate four different designs of glenospheres (SMR prosthesis); 36
      mm concentric (Standard), 36 mm eccentric, 44 mm concentric, and 44 mm eccentric
      glenospheres. The centre of rotation in each design was first established. The
      position of the humeral prosthesis was recorded in the plane of the scapula to
      compare the degree of adduction and the total range-of-motion. RESULTS: Eccentric
      glenospheres were found to improve range-of-motion by allowing a higher degree of
      adduction. Larger diameter glenospheres were found to improve range-of-motion by
      increasing adduction and abduction. Compared to the 36 mm concentric (standard)
      glenosphere, the 36 mm eccentric glenosphere improved adduction by 14.5 degrees,
      the 44 mm concentric glenosphere improved adduction by 11.6 degrees, the 44 mm
      eccentric glenosphere improved adduction by 17.7 degrees. CONCLUSION: Eccentric
      glenospheres with a center-of-rotation placed more inferiorly were shown to
      improve adduction. This design may reduce the clinical incidence of scapular
      notching.

PMID- 19393930
TI  - The effect of a local application of fibroblast growth factor-2 on tendon-to-bone
      remodeling in rats with acute injury and repair of the supraspinatus tendon.
AB  - METHODS: We investigated the effect of application of fibroblast growth factor
      (FGF)-2 on the tendon-to-bone remodeling of repaired supraspinatus tendon in rats
      subjected to bilateral detachment. FGF-2 (100 mg/kg) in a fibrin sealant or
      sealant alone was applied on the right and left shoulders, respectively. Twelve
      animals each at 2, 4, and 6 weeks after surgery were sacrificed for histological
      analysis (n = 5) and biomechanical Q1 testing (n = 7). RESULTS: Histologically,
      at 2 weeks, FGF-treated specimens had significantly higher tendon-to-bone
      insertion maturing scores then untreated specimens (P < .002). At 4 and 6 weeks,
      the scores of FGF-treated and untreated specimens were similar (P > .05).
      Biomechanically, FGF-treated specimens were stronger at 2 weeks (P = .001); at 4
      and 6 weeks, both specimens exhibited similar strength (P > .05). CONCLUSIONS:
      The initial tendon-to-bone remodeling was accelerated by a local application of
      FGF-2. This may represent a clinically important improvement in rotator cuff
      repair.

PMID- 19393931
TI  - The influence of type II coronoid fractures, collateral ligament injuries, and
      surgical repair on the kinematics and stability of the elbow: an in vitro
      biomechanical study.
AB  - PURPOSE: This study determined whether elbow stability could be restored with
      open reduction and internal fixation (ORIF) of type II coronoid fractures and
      evaluated the role of collateral ligament repair. METHODS: Passive varus and
      valgus and simulated active vertical motion were performed using an in vitro
      elbow motion simulator. Varus/valgus angle and internal/external rotation were
      measured with the coronoid intact, with 50% removed, and after ORIF. Testing was
      performed with the collateral ligaments detached and repaired. RESULTS: Vertical:
      stability was normal when both the lateral collateral ligament (LCL) and medial
      collateral ligament (MCL) were repaired, irrespective of the coronoid state.
      Kinematics were altered with a repaired LCL, incompetent MCL, and type II
      coronoid fracture (P < .05). Varus: LCL repair restored coronal stability but did
      not restore internal rotation (P < .05). CONCLUSIONS: These findings suggest that
      repair of type II coronoid fractures and injured collateral ligaments should be
      performed where possible. Over-tensioning the LCL, in the setting of MCL and
      coronoid deficiency, may contribute to instability.

PMID- 19393932
TI  - A brief fatigue inventory of shoulder health developed by quality function
      deployment technique.
AB  - BACKGROUND: The purpose of this study was to develop a diagnostic outcome
      instrument that has high reliability and low cost. The scale, called the Shoulder
      Fatigue Scale-30 Items (SFS-30) risk assessment, was used to determine the
      severity of patient neck and shoulder discomfort. METHODS: The quality function
      deployment (QFD) technique was used in designing and developing a simple medical
      diagnostic scale with high degree of accuracy. RESULTS: Research data can be used
      to divide the common causes of neck and shoulder discomfort into 6 core
      categories: occupation, cumulative, psychologic, diseases, diet, and sleep
      quality. The SFS-30 was validated by using a group of individuals who had been
      previously diagnosed with different levels of neck and shoulder symptoms. The SFS
      30 assessment determined that 78.57% of the participants experienced a neck and
      shoulder discomfort level above the SFS-30 risk curve and required immediate
      medical attention. CONCLUSION: The QFD technique can improve the accuracy and
      reliability of an assessment outcome instrument. This is mainly because the QFD
      technique is effective in prioritizing and assigning weight to the items in the
      scale. This research successfully developed a reliable risk assessment scale to
      diagnose neck and shoulder symptoms using QFD technique. This scale was proven to
      have high accuracy and closely represents reality.

PMID- 19393933
TI  - Assessing our patients: commentary on "A brief fatigue inventory of shoulder
      health developed by quality function deployment technique" and "Normal shoulder
      outcome score values in the young, active adult".

PMID- 19393934
TI  - Fracture of the scapular body: functional outcome after conservative treatment.
AB  - BACKGROUND: Scapular body fractures, irrespective of the number of fragments, are
      usually managed non-operatively, with favorable results. We evaluated results
      after non-operative management to determine the outcomes of scapular body
      fractures. METHODS: We evaluated 22 patients following a fracture of the scapular
      body that had been treated non-operatively. To assess the influence of
      accompanying injuries other than those of the involved limb, we used both patient
      oriented general health and shoulder-based outcome measures. RESULTS: In this
      series the functional outcome, reflected by the Disabilities of the Arm, Shoulder
      and Hand (DASH) score, the Simple Shoulder Test (SST) score and the range-of
      motion, showed a difference between multiple injured patient group and a group
      sustaining a isolated scapular fracture. There was no significant difference in
      the SF-36 scores of the overall group compared with an age-matched population
      control in any subcategory beside the subcategory social function. The SF-36
      scores of the multitrauma patient group were significantly lower than the scores
      of the age-matched population controls in several subcategories. CONCLUSION:
      Whereas isolated scapular body fractures healed leading to a functional shoulder
      score level equal to the general population and a range of motion equal to the
      uninjured contralateral shoulder, the multitrauma patient group showed a less
      favorable outcome.

PMID- 19393935
TI  - Results after 562 total elbow replacements: a report from the Norwegian
      Arthroplasty Register.
AB  - BACKGROUND: The aim of this study was to give results of elbow arthroplasty for a
      relatively large population and compare different prosthesis brands and different
      patient subgroups. METHODS: Between 1994 and 2006, 562 total elbow replacement
      operations were reported to the Norwegian Arthroplasty Register. Revisions of
      prostheses were shown using Kaplan-Meier failure curves, and risk of revision was
      calculated using Cox regression analysis. RESULTS: The overall 5- and 10-year
      failure rates were 8% and 15%, respectively. There were only minor differences
      between the different implants. Patients who developed traumatic arthritis after
      fracture had the worst prognosis compared with inflammatory arthritis (P = .005).
      Risk of revision was also increased when the ulnar component was inserted without
      cement (P = .02.) CONCLUSIONS: Good results in terms of prosthesis survival were
      obtained with total elbow arthroplasty, although results were worse than for knee
      and hip arthroplasties. The best results were achieved in patients with
      inflammatory arthritis.

PMID- 19393936
TI  - Effectiveness of revision following linked versus unlinked total elbow
      arthroplasty.
AB  - PURPOSE: The purpose of this study is to specifically evaluate the implications
      of unlinked and linked designs on the survivorship of revision surgery. METHODS:
      Between 1972 and 1990, 352 linked and 151 unlinked prostheses were inserted at
      our institution. One-hundred and twenty-two elbows (24%) underwent subsequent
      revision: 55 linked (16%) and 67 unlinked (44%). Survivorship of the initial and
      revision total elbow replacement was calculated using a Kaplan-Meier analysis.
      Comparisons were made between revisions done after a failed primary linked or
      unlinked designs. The unlinked revised to a linked device was more reliable than
      when revised to another unlinked device: 1 year survival 84% compared to 47%.
      RESULTS: Initial survival was 56% at 367 months and 84% at 371 months for the
      unlinked and linked cohorts, respectively (P < .001). A second revision was
      required in 12 of the 35 elbows (30%) in the linked cohort and 14 of the 50
      elbows (28%) in the unlinked. CONCLUSIONS: At our institution, primary linked
      implants display significantly better long-term survivorship (P < .001) than did
      the unlinked designs. Unlinked designs are most reliably converted to a linked
      implant.

PMID- 19393937
TI  - Are standardized patient self-reporting instruments applicable to the evaluation
      of ulnar neuropathy at the elbow?
AB  - BACKGROUND: This study attempts to confirm that the Disabilities of Arm, Shoulder
      and Hand (DASH) Outcome Measure self-administered questionnaire is valid
      specifically for ulnar neuropathy at the elbow. Validity of the Levine-Katz
      questionnaire for ulnar neuropathology compared with DASH was also studied.
      MATERIALS AND METHODS: Forty-eight patients with isolated ulnar nerve surgery
      completed a 6-month evaluation. Patients were assigned a clinical stage. The DASH
      and Levine-Katz questionnaires were administered, and pinch and grip strength
      were measured preoperatively and postoperatively. Levine-Katz questionnaires were
      correlated with DASH to establish criterion validity. Construct validity was
      tested by determining a relationship between scores and clinical stages and by
      comparing scores preoperatively and postoperatively. RESULTS: There was a high
      correlation between DASH scores and symptom severity and functional status.
      Although correlations were significant between DASH and biomechanical measures,
      correlation coefficients were lower. Postoperatively, all measures improved
      significantly. CONCLUSION: This study confirms that scores on the DASH
      questionnaire reflect the clinical staging of ulnar neuropathy at the elbow.

PMID- 19393938
TI  - Computer assisted surgery of the distal humerus can employ contralateral images
      for pre-operative planning, registration, and surgical intervention.
AB  - BACKGROUND: Bone loss at the distal humerus can lead to errors in the
      identification of the elbow's flexion-extension axis. Referencing the anatomy of
      the contralateral (uninjured) elbow may prove beneficial in accurately defining
      this axis. The objective of this study was to compare distal humeral morphology
      between paired specimens and determine whether geometric differences exist.
      METHODS: Medical CT images of 25 paired, dry cadaveric, distal humeri were
      acquired and a range of anatomic characteristics were measured, following
      registration of each pair to a common coordinate system. RESULTS: The
      anthropometric features of the distal humerus were similar from side-to-side,
      with differences on the order of 1.0 degrees and 0.5 mm. CONCLUSIONS:
      Preoperative imaging of the contralateral normal elbow may be employed in
      patients with peri-articular bone loss, where referencing anatomic landmarks of
      the injured side is not possible.

PMID- 19393939
TI  - Long-term results of remodeling of lateral condylar prominence after lateral
      closed-wedge osteotomy for cubitus varus.
AB  - BACKGROUND: Despite the ability of lateral closed-wedge osteotomy for cubitus
      varus deformity to restore carrying angle and preserve elbow motion, there have
      been reports of poor cosmetic appearance of the elbow because of lateral condylar
      prominence. METHOD: We evaluated long-term results of remodeling of lateral
      condylar prominence after osteotomy in 11 patients (7 of the prepuberty group, 4
      of the postpuberty group). The follow-up period ranged from 4.7 to 14.2 years
      (average, 10). RESULTS: The mean preoperative and postoperative lateral condylar
      prominence index (LCPI) of the affected elbow were -1.2% and 36%, respectively.
      At final follow-up, the mean LCPI of the corrected elbow was 11.1%. In the
      prepubertal group, the mean LCPI decreased from 41.2% after surgery to 5.2% at
      final follow-up, whereas it decreased from 26.8% to 21.3% in the postpubertal
      group. The difference in reduction between the mean postoperative LCPI and the
      mean LCPI at final follow-up in the prepubertal group (36%) was greater than in
      the postpubertal group (5.4%) (P = .006). CONCLUSION: Lateral closed-wedge
      osteotomy is a relatively simple and effective procedure for correction of
      cubitus varus deformity before puberty, allowing cosmetically pleasing remodeling
      of lateral condylar prominence.

PMID- 19393940
TI  - Microvascular reconstructive surgery of the face: preface.

PMID- 19393941
TI  - Reconstruction of the scalp.
AB  - The scalp provides a relatively limited amount of excess tissue that can be used
      in reconstructing significant scalp defects, which arise most often from
      oncologic resection or traumatic loss. Scalp reconstruction encompasses a broad
      spectrum of flaps, grafts, and techniques that should be readily available to the
      facial plastic surgeon treating this patient population. Meticulous attention to
      detail, particularly in the planning and early postoperative periods, is
      associated with gratifying results in the majority of patients. This article
      presents defect analysis and discussion of reconstruction options, with figures
      of successful reconstructive surgeries.

PMID- 19393942
TI  - The total nasal defect and reconstruction.
AB  - The structures of the nose are arguably the most complex within the face to
      reconstitute when absent. Total nasal reconstruction has evolved to encompass
      advanced surgical techniques in an effort to achieve increasingly satisfactory
      cosmetic results while restoring nasal function that mimics the function of a
      patient's natural nose. In this article, the history of total nasal defects and
      their reconstruction, relevant nasal anatomy, etiologies of the defect, and the
      surgical approaches to reconstructing each of the three-layered structure of the
      nose (ie, nasal skin, cartilage/bone, and lining mucosa) are explored.

PMID- 19393943
TI  - Microvascular reconstruction of major lip defects.
AB  - Reconstruction of extensive lip defects is a challenging task for reconstructive
      microsurgeons. This article reviews the goals of lip reconstruction after major
      ablative or traumatic lip losses and outlines the free flap options available to
      achieve these goals.

PMID- 19393944
TI  - Reconstruction of the midface and maxilla.
AB  - The maxilla and midface have an important aesthetic and functional role. Their
      reconstruction after surgical ablation is a complex problem. The historical
      development of reconstruction of the midface, classification systems of maxillary
      defects, and descriptions of reconstructive options are presented.

PMID- 19393945
TI  - Microvascular reconstruction of the orbital complex.
AB  - Extensive skin, paranasal, and skull base malignancies often invade the orbit
      necessitating the removal of the orbital contents to achieve local tumor control.
      Defects of this region often create a communication between the intracranial and
      extracranial contents that involves a large volume of skin, soft tissue, and
      bone. Local and regional tissue alone is rarely adequate to repair these defects.
      In contrast, free tissue transfer can provide vascularized skin, soft tissue, and
      bone that can reliably separate the extracranial and intracranial compartments
      and restore the bony and soft tissue architecture of the orbitomaxillary complex.
      This article summarizes the approach to orbitomaxillary reconstruction and
      discusses the use of free tissue transfer in the rehabilitation of this complex
      region.

PMID- 19393946
TI  - Maxillofacial trauma reconstruction.
AB  - Maxillofacial trauma caused by severe ballistic or avulsion injuries to the face
      creates complex composite defects. The essential difference between most blunt
      facial injuries and ballistic or avulsive facial injuries is the severity of the
      soft and hard tissue loss and damage. Application of modern principles of
      fracture management and wound care, however, allows restoration of the facial
      framework until a healthy tissue bed is achieved for definitive repair. Free
      tissue transfer has made it possible to bring well-vascularized bone and soft
      tissue into a hostile wound environment with excellent survival of the flap
      tissues. This has allowed for simultaneous reconstruction of the bony facial
      skeleton and the overlying soft tissue soon after injury.

PMID- 19393947
TI  - Reconstruction of periauricular and temporal bone defects.
AB  - Large periauricular and temporal bone defects most commonly follow resection of
      advanced nonmelanoma skin cancers. Reconstruction aims to cover the cutaneous
      defect and adjacent vital structures with the ability to heal in an irradiated
      field and withstand further treatment. Preferred reconstructions are class I,
      cervicofacial rotation or radial forearm free flap; class II, anterolateral
      thigh; and class II, rectus abominis free flap. Ancillary procedures, especially
      for associated facial paralysis, often are required. Although free flap
      reconstruction provides rapid wound healing, local and regional flaps are
      alternatives for patients unable to tolerate prolonged anesthesia and for use
      after recurrence or complications.

PMID- 19393948
TI  - Parotid defects.
AB  - Parotidectomy is a widely performed procedure for various indications, including
      benign and malignant conditions. For malignant neoplasms of the parotid gland or
      metastatic disease, it may be performed in conjunction with cheek or temple skin
      resection, facial nerve sacrifice, or composite resection of a portion of the
      mandible. There are various options for reconstruction depending on the extent of
      resection. This article discusses various reconstructive options following
      parotidectomy and other ablative procedures that are often performed in
      conjunction. Reconstruction of parotidectomy defects associated with lateral
      temporal bone resection is discussed elsewhere in this issue.

PMID- 19393949
TI  - Facial transplantation: the next frontier in head and neck reconstruction.
AB  - Facial reconstruction poses a unique surgical challenge-restoring the aesthetic
      form and function of the face. Established techniques for reconstruction include
      skin grafts, local cutaneous tissue flaps, and free flap autografts. The anatomic
      complexity of the face renders it challenging, however, to obtain a successful
      cosmetic and functional result. The success of recent hand, knee joint, and
      larynx allotransplantation and advances in immunosuppressive regimens have pushed
      the technical frontiers of composite tissue transfer to include partial facial
      transplantation. This article reviews current techniques for reconstruction of
      facial defects, with a focus on the microsurgical, immunologic, and ethical
      considerations of facial allotransplantation.

PMID- 19393950
TI  - Free tissue transfer in the reconstruction of massive skin cancer.
AB  - Skin cancer arising in the head and neck is a common occurrence. Although the
      vast majority of these cancers can be treated with simple excision and local
      reconstruction there is a subset of patients who have massive tumors that require
      composite tissue resection. These patients are best reconstructed with free
      tissue transfer. Acceptable functional and cosmetic results can be expected. Long
      term survival is excellent in patients who have negative margins.

PMID- 19393951
TI  - US supermarkets redefine antibiotic misuse.

PMID- 19393952
TI  - H5N1 influenza vaccination policy in Japan.

PMID- 19393953
TI  - Poor-quality medicines in developing countries.

PMID- 19393954
TI  - Not so SMART?

PMID- 19393955
TI  - Funding of drugs: do vaccines warrant a different approach?

PMID- 19393957
TI  - The hazards of pet ownership.

PMID- 19393958
TI  - Gram-positive toxic shock syndromes.
AB  - Toxic shock syndrome (TSS) is an acute, multi-system, toxin-mediated illness,
      often resulting in multi-organ failure. It represents the most fulminant
      expression of a spectrum of diseases caused by toxin-producing strains of
      Staphylococcus aureus and Streptococcus pyogenes (group A streptococcus). The
      importance of Gram-positive organisms as pathogens is increasing, and TSS is
      likely to be underdiagnosed in patients with staphylococcal or group A
      streptococcal infection who present with shock. TSS results from the ability of
      bacterial toxins to act as superantigens, stimulating immune-cell expansion and
      rampant cytokine expression in a manner that bypasses normal MHC-restricted
      antigen processing. A repetitive cycle of cell stimulation and cytokine release
      results in a cytokine avalanche that causes tissue damage, disseminated
      intravascular coagulation, and organ dysfunction. Specific therapy focuses on
      early identification of the illness, source control, and administration on
      antimicrobial agents including drugs capable of suppressing toxin production (eg,
      clindamycin, linezolid). Intravenous immunoglobulin has the potential to
      neutralise superantigen and to mitigate subsequent tissue damage.

PMID- 19393959
TI  - Incubation periods of acute respiratory viral infections: a systematic review.
AB  - Knowledge of the incubation period is essential in the investigation and control
      of infectious disease, but statements of incubation period are often poorly
      referenced, inconsistent, or based on limited data. In a systematic review of the
      literature on nine respiratory viral infections of public-health importance, we
      identified 436 articles with statements of incubation period and 38 with data for
      pooled analysis. We fitted a log-normal distribution to pooled data and found the
      median incubation period to be 5.6 days (95% CI 4.8-6.3) for adenovirus, 3.2 days
      (95% CI 2.8-3.7) for human coronavirus, 4.0 days (95% CI 3.6-4.4) for severe
      acute respiratory syndrome coronavirus, 1.4 days (95% CI 1.3-1.5) for influenza
      A, 0.6 days (95% CI 0.5-0.6) for influenza B, 12.5 days (95% CI 11.8-13.3) for
      measles, 2.6 days (95% CI 2.1-3.1) for parainfluenza, 4.4 days (95% CI 3.9-4.9)
      for respiratory syncytial virus, and 1.9 days (95% CI 1.4-2.4) for rhinovirus.
      When using the incubation period, it is important to consider its full
      distribution: the right tail for quarantine policy, the central regions for
      likely times and sources of infection, and the full distribution for models used
      in pandemic planning. Our estimates combine published data to give the detail
      necessary for these and other applications.

PMID- 19393960
TI  - Infection control in the management of highly pathogenic infectious diseases:
      consensus of the European Network of Infectious Disease.
AB  - The European Network for Infectious Diseases (EUNID) is a network of clinicians,
      public health epidemiologists, microbiologists, infection control, and critical
      care doctors from the European member states, who are experienced in the
      management of patients with highly infectious diseases. We aim to develop a
      consensus recommendation for infection control during clinical management and
      invasive procedures in such patients. After an extensive literature review, draft
      recommendations were amended jointly by 27 partners from 15 European countries.
      Recommendations include repetitive training of staff to ascertain infection
      control, systematic use of cough and respiratory etiquette at admission to the
      emergency department, fluid sampling in the isolation room, and analyses in
      biosafety level 3/4 laboratories, and preference for point-of-care bedside
      laboratory tests. Children should be cared for by paediatricians and intensive
      care patients should be cared for by critical-care doctors in high-level
      isolation units (HLIU). Invasive procedures should be avoided if unnecessary or
      done in the HLIU, as should chest radiography, ultrasonography, and renal
      dialysis. Procedures that require transport of patients out of the HLIU should be
      done during designated sessions or hours in secure transport. Picture archiving
      and communication systems should be used. Post-mortem examination should be
      avoided; biopsy or blood collection is preferred.

PMID- 19393961
TI  - Stenotrophomonas maltophilia: an emerging opportunist human pathogen.
AB  - Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen
      in the debilitated host. S maltophilia is not an inherently virulent pathogen,
      but its ability to colonise respiratory-tract epithelial cells and surfaces of
      medical devices makes it a ready coloniser of hospitalised patients. S
      maltophilia can cause blood-stream infections and pneumonia with considerable
      morbidity in immunosuppressed patients. Management of infection is hampered by
      high-level intrinsic resistance to many antibiotic classes and the increasing
      occurrence of acquired resistance to the first-line drug co-trimoxazole.
      Prevention of acquisition and infection depends upon the application of modern
      infection-control practices, with emphasis on the control of antibiotic use and
      environmental reservoirs.

PMID- 19393962
TI  - Chagasic encephalitis in HIV patients: common presentation of an evolving
      epidemiological and clinical association.
AB  - We present a case of chagasic meningoencephalitis reactivation in an HIV-infected
      woman with advanced immunosuppression. Prolonged survival was attained with
      antiparasitic therapy and secondary prophylaxis, in conjunction with the use of
      highly-active antiretroviral therapy. The geographic expansion of the HIV
      epidemic around the world coupled with global migration and international travel
      have created a favourable situation for Trypanosoma cruzi and HIV coinfection.
      The clinical manifestations of Chagas disease in HIV-positive people usually
      represent reactivation and not acute infection with T cruzi (coinfection).
      Symptomatic reactivation of chronic latent T cruzi infection can be triggered by
      severe immunosuppression associated with HIV infection. In this setting, Chagas
      disease reactivation often presents as meningoencephalitis resembling toxoplasma
      encephalitis. We review, in this Grand Round, the clinical manifestations,
      diagnostic approach, pathogenesis, natural history, treatment, prognosis, and
      prevention of Chagas disease reactivation among HIV-infected people with an
      emphasis on CNS manifestations.

PMID- 19393963
TI  - There's no place like home.

PMID- 19393964
TI  - Why not home dialysis?

PMID- 19393965
TI  - Peritoneal dialysis patient selection: characteristics for success.
AB  - This review focuses on the strategy of patient selection for peritoneal dialysis
      (PD) based on published epidemiology studies and observational data. With the
      success of the PD first model in Hong Kong, experience shows that there is no
      particular patient group that cannot be put on PD except those who have major
      problems in the abdomen. Incident patients should be offered the choice to
      receive PD at the start of dialysis in order to preserve better the residual
      renal function. Concern has also been expressed for a time-dependent negative
      impact of PD on survival, although PD in general provides survival advantage at
      least during the first few years after the start of dialysis. Regular patient
      review is essential to allow prompt adjustment of the dialysis regimen and
      modality when required. Accumulating research suggests that center size has a
      significant effect on the patient and technique survival of patients undergoing
      PD. Comorbid diabetes, large and small body size, peritoneal membrane transport
      status, elderly age group, and socioeconomic status are important patient factors
      to consider. Good clinical and psychosocial care of the PD patients are essential
      as well as the attention to their compliance. Enhanced training to medical and
      nursing personnel on PD is one of the key success factors for improving its
      utilization and outcome.

PMID- 19393966
TI  - Nocturnal home hemodialysis and short daily hemodialysis compared with kidney
      transplantation: emerging data in a new era.
AB  - Nocturnal home hemodialysis (NHD) and short daily hemodialysis (SDHD) are novel
      forms of renal replacement therapies gaining increased attention because of the
      reversal of many end-stage renal disease (ESRD)-associated pathophysiological
      perturbations that are not correctable with conventional dialysis. New evidence
      suggests that such intensive dialysis is associated with improved survival
      compared with traditional 3-times-a-week hemodialysis and may have a survival
      advantage comparable to that seen with deceased donor transplantation. If
      confirmed, these new findings have significant implications for the delivery of
      care to the ESRD population and warrant further study.

PMID- 19393967
TI  - Cardiovascular effects of home intensive hemodialysis.
AB  - Cardiovascular mortality remains the leading cause of death in patients with end
      stage renal disease. Frequent home hemodialysis in the form of short daily
      hemodialysis and nocturnal home hemodialysis has been suggested to correct
      multiple cardiovascular surrogate endpoints in observational and randomized
      controlled studies. This review discusses recent advances of intensive
      hemodialysis on important cardiovascular outcomes including blood pressure
      control and cardiovascular geometry and function. Its impact on calcium-phosphate
      metabolism and anemia management as they relate to cardiovascular outcomes are
      highlighted.

PMID- 19393968
TI  - Sleep disorders and home dialysis.
AB  - Sleep disorders, such as restless legs, periodic limb movements and sleep apnea,
      and sleep complaints such as insomnia and daytime sleepiness, are very common in
      end-stage renal disease patients despite treatment with 3-times-a-week
      conventional hemodialysis. If left untreated, they are likely to impair quality
      of life and may alter cardiovascular outcomes in this patient population. Home
      dialysis has the potential to improve sleep disorders by offering more effective
      dialysis than conventional modalities. Although there has been little direct
      comparison between the impact of home dialysis and conventional dialysis on sleep
      disorders, there is evidence that both nocturnal peritoneal dialysis and
      nocturnal hemodialysis improve sleep apnea. The impact of home dialysis on other
      sleep disorders and sleep complaints is less impressive, but the data, thus far,
      have been limited. Further research is required to evaluate the impact of home
      dialysis on all sleep disorders and sleep complaints in this patient population
      and to determine whether this improves quality of life and cardiovascular
      morbidity and mortality.

PMID- 19393969
TI  - The United States' perspectives on home dialysis.
AB  - Home dialysis in the United States, both home hemodialysis and peritoneal
      dialysis, peaked in the early 1990s. Since then, there has been a striking
      increase in the numbers and proportion of patients on in-center home hemodialysis
      (HD). As of 2008, there were approximately 27,000 patients on peritoneal dialysis
      (PD) and 2,455 on home HD with over 300,000 on in-center HD. There are multiple
      barriers to home dialysis in the United States, including lack of adequate
      patient education on modalities prior to starting dialysis, physician competence
      with home dialysis, lack of infrastructure in many programs for home dialysis,
      and a misinterpretation of literature and research with selection bias that
      suggests higher mortality on PD versus in-center HD. These barriers to home
      dialysis can be overcome.

PMID- 19393970
TI  - The economics of home dialysis: acting for the individual while planning
      responsibly for the population.
AB  - Traditional medical education paradigms tend not to focus on health economics and
      economic evaluation. This has led to a culture in which bedside clinicians simply
      allocate health care resources made available to them, with often minimal input
      as to what these resources are at the population or health care system level.
      Life sustaining chronic dialysis therapies for end-stage renal disease are
      heterogeneous in terms of health care costs and the quality of life provided to
      patients receiving them. From the traditional clinician's perspective, they may
      be considered equivalent because there are no well-designed randomized control
      trials establishing the superiority of one particular dialysis modality in terms
      of all-cause mortality or cardiovascular events. The intent of this review is to
      provide clinicians practicing in the area of chronic kidney disease some insights
      into the concepts of economic evaluation and how it may be integrated into
      clinical decision making at a programmatic level while not compromising
      individual patient care at the bedside. An epidemiologic perspective will be used
      to help frame how the implementation of home dialysis modalities vary depending
      on local health policies in place. Lessons learned by regional nephrology care
      systems may be readily transferable to other jurisdictions in augmenting the
      uptake of home dialysis modalities where they are dwindling or struggling to
      grow. A high-level understanding of economic data in this area may help influence
      health policy in the direction of the most efficient provision of dialysis to
      patients while not adversely affecting their quality of life or health outcomes.

PMID- 19393971
TI  - International variations and trends in home hemodialysis.
AB  - Home hemodialysis, once a valid, viable dialysis choice, faded as facility-based
      care was preferentially funded and supported through the 1970s and 1980s. It was
      simply more comfortable for providers, physicians, and nurses to capture dialysis
      patients through clinic schedules and clinical protocols. Home patients were
      unpredictable, out of sight and out of control, trouble, and best avoided. This
      was so except in Australia and New Zealand where funding and support remained
      strong for what was seen there as an effective, outcome-rich, and cost-effective
      modality. The renaissance of home hemodialysis began in Canada when home-based
      nocturnal dialysis emerged in the 1990s. Home patients soon appreciated the self
      determination and re-employment opportunities that overnight dialysis delivered.
      This article explores the origins, the near demise, the foundations of renewal,
      and the now-expanding potential of home and nocturnal hemodialysis in regions as
      diverse as North America, Australia and New Zealand, South East Asia, the United
      Kingdom, and Finland. Home dialysis fed by cost containment, outcome success,
      patient acceptance, and new smart equipment has emerged as a bright new modality
      option. Trainee nephrologists would be wise to take more notice as this near
      ghost of the past forges an exciting future.

PMID- 19393972
TI  - Technical advances in home dialysis.
AB  - Recently, multiple initiatives to produce dedicated and simplified hemodialysis
      machines for home hemodialysis (HHD) have begun. Most have been designed for
      short daily hemodialysis 6 times per week. Only 1 machine currently has Food and
      Drug Administration clearance for HHD, but others are in clinical trial or are
      soon to be. There has been a trend toward using sorbent technology to allow
      online regeneration of dialysate to facilitate portability and to reduce machine
      size and reduce water consumption. Many of the machines are intended to be a
      stepping stone to a wearable artificial kidney (WAK). A WAK using peritoneal
      dialysis rather than hemodialysis is also in the development stage.

PMID- 19393973
TI  - Nicotinic receptors and nicotine addiction.

PMID- 19393974
TI  - Purification and characterization of alpha-amylase from safflower (Carthamus
      tinctorius L.) germinating seeds.
AB  - alpha-Amylase (alpha-1-4 D-glucan glucanohydrolase EC 3.2.1.1) crude extract was
      obtained from safflower (Carthamus tinctorius L.) cotyledons excised from 5-day
      old dark grown seedlings. The enzyme was purified by precipitating the crude
      extract with ammonium sulphate at 20-60% saturation, and then by subjecting this
      fraction to affinity chromatography on a beta-cyclodextrin-Sepharose 6B column.
      The active fraction was dialysed and concentrated. An overall purification of
      about 131 folds with an activity yield of 81.25% was achieved. The molecular mass
      of purified enzyme determined by SDS-PAGE was 35 kD. When the purified alpha
      amylase was subjected to gel electrophoresis followed by negative staining, only
      one band of active protein was detected. Its maximal activity was in the pH 6.0
      and at a temperature of 55 degrees C. This enzyme was activated by Ca(2+) and
      inhibited by Fe(2+).

PMID- 19393975
TI  - [Biology of arterial ageing and arteriosclerosis].
AB  - Arterial ageing - arteriosclerosis - is characterised by both thickening and
      stiffening of the walls of large and medium arteries. The molecular and cellular
      mechanisms (i.e. endothelial dysfunction, matrix remodelling, ...) involved in
      this process are complex, and at least in part common to atherosclerotic injury.
      Arterial stiffness is strongly associated with cardiovascular disease and an
      increased risk of morbidity and mortality. The aim of this review is to provide
      an update on the pathophysiology and the biological process of arterial ageing
      and to underline the main difference with atherosclerosis damage process in
      particularly during the calcification step.

PMID- 19393976
TI  - [In vitro activity of different fungicides on the growth in Mycosphaerella
      fijiensis var. difformis Stover and Dickson, Cladosporium musae Morelet and
      Deightoniella torulosa (Syd.) Ellis, isolated parasites of the banana
      phyllosphere in the Ivory Coast].
AB  - In Cote-d'Ivoire, banana leaf surfaces are attacked by Mycosphaerella fijiensis
      var. difformis, Cladosporium musae, and Deigthonielle torulosa. Control is based
      on fungicides recommanded for Mycosphaerella fijiensis. Fungicides belonging to
      triazoles and strobilurines types were added, at different concentrations, to the
      PDA medium, using this PDA medium containing no fungicide as the control.
      Mycelium disc and spores of Cladosporium musae, Mycosphaerella fijiensis and
      Deightoniella torulosa were put on the different media. Total inhibition of
      mycelium growth of every fungus on the PDA amended with propiconazole was
      observed. The fungicides used show different activities according to their
      concentration and their mode of action. The application of a fungicide should
      talke into account the pathogenic fungus involved in the leaf attacked. Against
      Mycosphaerella fijiensis var. difformis, the Ci(50) are different according to
      the concentrations (0.44 to 1.06 ppm). Correlations ranked from 0.71 to 0.91 are
      also different according to fungicide used. The Ci(50) of Cladosporium musae
      (0.10 to 2.44 ppm) and Deightoniella torulosa (0.26 to 0.52 ppm) are different
      and their correlations are respectively 0.78 to 0.99 and 0.86 to 0.95. An
      assessment of the sensitivity of parasitic fungi of banana can be made by
      mycelium growth measurement of fungi isolated from resistance zones.

PMID- 19393977
TI  - A new, isolated and endangered relict population of dwarf pine (Pinus mugo Turra)
      in the northwestern Alps.
AB  - Dwarf pines were discovered in 2004 during a paleoecological survey in the Mont
      Cenis massif (Savoy, France). These dwarf pines are the sole natural and
      spontaneous population in the NW French Alps of Pinus mugo Turra, ssp. mughus
      (Scop.) O. Schwarz. The population, fragile in light of the individual numbers,
      is currently isolated, but likely results from populations that would have
      covered larger areas during the Lateglacial or the early-Holocene, from the SW
      Alps (France) toward the Mont Cenis, throughout the Susa valley (Italy). With a
      fragmented distribution area of dwarf pine, the future of the Mont Cenis
      population seems altered due to important necroses observed on the topmost part
      of pine crowns, except for individuals that do not grow in the local ski station
      area. We stress the need for a conservation program to preserve this natural
      population, the sole known in the NW French Alps.

PMID- 19393978
TI  - Some water chemistry parameters of breeding habitats of the Caucasian salamander,
      Mertensiella caucasica in the Western Lesser Caucasus.
AB  - Selection of breeding habitat plays a fundamental role in the reproductive
      success of urodeles and anurans. We studied the influence of water chemistry
      variables on the selection of a specific water resource as breeding habitat in
      Mertensiella caucasica. To determine the influence of water chemistry parameters
      on their habitat selection, we surveyed a total of 45 small river, streams and
      brooks in the Western Lesser Caucasus (northeastern Turkey and southwestern
      Georgia). The water samples taken from these localities were analyzed for 14
      chemical variables and the results submitted to multiple logistic regression
      analysis in order to evaluate the influence of these parameters on the presence
      or absence of the species in the localities. Of these parameters, chloride
      concentration influenced the breeding habitat selection of Mertensiella caucasica
      significantly.

PMID- 19393979
TI  - Diversity and nest site selection of social wasps along Guianese forest edges:
      assessing the influence of arboreal ants.
AB  - We examined 424 nests belonging to 61 wasp species along 5 km of rainforest edges
      in French Guiana (ca. 15,235 plants monitored), and estimate that we recorded up
      to 73% of the local social wasp fauna. This baseline study was complemented by a
      long-term survey of the same area and the examination of isolated trees
      (permitting us to record two additional species, resulting in a total of 63 wasp
      species). Our results form a continuum from species avoiding nesting on any plant
      (6.5% of the wasp species) to species nesting on plants but avoiding those
      sheltering ant nests (82%), to, finally, wasps nesting in association with
      arboreal ants known to divert army ant raids (11.5%). Consequently, this study
      documents that most wasp species select plants possibly repulsive to arboreal
      ants, while associations with arboreal ants, although confirmed here, have been
      overrepresented in the literature.

PMID- 19393980
TI  - Morphological identification of sibling species: the case of West African
      Mastomys (Rodentia: Muridae) in sympatry.
AB  - In this study, we investigate skull size and shape differentiation between
      sibling species of Mastomys with the aim to characterize and discriminate three
      sympatric species found in West Africa: M. huberti, M. erythroleucus and M.
      natalensis. A total of 133 genetically determined specimens were used for the
      morphometric analyses. Statistical analyses clearly demonstrated that the three
      species largely overlapped in centroid size (M. erythroleucus tends to be larger
      on average than the M. huberti and M. natalensis) but they exhibited large
      differences in skull shape. The current study focused on skull shape, and allowed
      us to discriminate three morphological groups that are congruent with the three
      species suggested by molecular identification (90% of the individuals are
      correctly assigned by cross-validated classifications). In the Mastomys, the
      evolution of cranial length and shape may be influenced by competitive pressure
      between closely related species separated by ecological segregation. This source
      of variability could possibly induce character displacement between species of
      Mastomys.

PMID- 19393981
TI  - Anopheles of Bolivia: new records with an updated and annotated checklist.
AB  - Anopheles squamifemur has been identified from CDC light trap collections carried
      out at Arca de Israel, a small community located in the extreme north-east of
      Bolivia (Pando Department) on the banks of the river Madera, on the border with
      Brazil. Anopheles costai and An. forattinii have been identified in place of An.
      mediopunctatus which has been removed from the Bolivian list of Anopheles
      species. The first identification of An. trinkae in Bolivia by Dr. J.C. Lien in
      1984 is cleared. The presence of An. deaneorum in Bolivia has been confirmed by
      our mosquito captures carried out in Guayaramerin (Pando Department, north-east
      of Bolivia), a border city separated from the type locality of An. deaneorum, the
      Brasilian city of Guajara-Mirin, by the large Mamore River. These new findings
      increase to 43 the total number of known Anopheles species for Bolivia for which
      an updated and partially annotated checklist is given.

PMID- 19393982
TI  - Food transport in ants: Do Lasius niger foragers maximize their individual load?
AB  - The decision for a Lasius niger forager to lay a chemical trail and launch
      recruitment to a food source is governed by an internal individual threshold. The
      value of this threshold triggering chemical communication is not set by the
      maximal capacity of the crop. Actually, trail-laying ants are still able to drink
      additional food encountered on their homeward journey. The partial filling of the
      crop by trail-laying ants may be a means for the ants to shorten foraging trips
      and to speed up the information updating within the nest. Moreover, by partially
      filling their crop, foragers keep a potential for sampling resources and for
      tasting other encountered food sources.

PMID- 19393983
TI  - Complications associated with sickle cell trait: a brief narrative review.
AB  - Sickle cell trait occurs in approximately 300 million people worldwide, with the
      highest prevalence of approximately 30% to 40% in sub-Saharan Africa. Long
      considered a benign carrier state with relative protection against severe
      malaria, sickle cell trait occasionally can be associated with significant
      morbidity and mortality. Sickle cell trait is exclusively associated with rare
      but often fatal renal medullary cancer. Current cumulative evidence is convincing
      for associations with hematuria, renal papillary necrosis, hyposthenuria, splenic
      infarction, exertional rhabdomyolysis, and exercise-related sudden death. Sickle
      cell trait is probably associated with complicated hyphema, venous thromboembolic
      events, fetal loss, neonatal deaths, and preeclampsia, and possibly associated
      with acute chest syndrome, asymptomatic bacteriuria, and anemia in pregnancy.
      There is insufficient evidence to suggest an independent association with
      retinopathy, cholelithiasis, priapism, leg ulcers, liver necrosis, avascular
      necrosis of the femoral head, and stroke. Despite these associations, the average
      life span of individuals with sickle cell trait is similar to that of the general
      population. Nonetheless, given the large number of people with sickle cell trait,
      it is important that physicians be aware of these associations.

PMID- 19393984
TI  - Cystatin C in acute heart failure without advanced renal impairment.
AB  - BACKGROUND: The prognostic value of cystatin C relative to glomerular filtration
      rate (GFR) estimated by the Modification of Diet in Renal Disease Study (MDRD)
      equation modified for Japan has not been investigated in acute heart failure
      patients with normal to moderately impaired renal function. More accurate
      detection of mild renal impairment might improve the risk stratification of heart
      failure patients, especially patients with normal to moderately impaired renal
      function. METHODS: Cystatin C and creatinine levels were measured on admission in
      328 consecutive patients hospitalized for worsening chronic heart failure with a
      GFR estimated by MDRD equation modified for Japan >or=30 mL/min/1.73 m(2).
      RESULTS: During a median follow-up period of 915 days, there were 52 (16%)
      cardiac deaths. In stepwise Cox regression analyses including cystatin C and GFR
      estimated by MDRD equation modified for Japan (either as continuous variables or
      as variables categorized into quartiles), cystatin C (P <.0001), but not GFR
      estimated by MDRD equation modified for Japan, was independently associated with
      cardiac mortality. Adjusted relative risk according to the quartiles of these
      markers and Kaplan-Meier analyses revealed that the cystatin C was a better
      marker to separate low-risk from high-risk patients. Furthermore, receiver
      operating characteristic curve analyses of these markers revealed that cystatin C
      showed a higher precision in predicting cardiac mortality. CONCLUSION:
      Measurements of cystatin C might improve early risk stratification compared with
      GFR estimated by MDRD equation modified for Japan in acute heart failure patients
      with normal to moderately impaired renal function.

PMID- 19393985
TI  - Variation in fetal ultrasound biometry based on differences in fetal ethnicity.
AB  - OBJECTIVE: The objective of the study was to evaluate whether fetal ultrasound
      biometry is affected by variation in fetal ethnicity compared with white
      controls. STUDY DESIGN: This was a retrospective observational study of
      ultrasound biometry in pregnant women with accurate gestational age. RESULTS:
      Three hundred five white, 370 Asian, 895 part Hawaiian, 76 Pacific Islander, and
      311 white Asian fetuses were analyzed. At 18 weeks gestation femur length was
      significantly shorter in Asian and white Asian. Humerus length was significantly
      shorter in Asian, part Hawaiian, and white Asian. White genetic sonogram was
      positive 14% for femur and 15% for humerus. The following was found: Asian 29%
      femur (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.70-3.92), 25%
      humerus (OR, 1.86; 95% CI, 1.23-2.82); part Hawaiian 21% femur (OR, 1.67; 95% CI,
      1.14-2.45), 23% humerus (OR, 1.64; 95% CI, 1.13-2.38); Pacific Islander 27% femur
      (OR, 2.37; 95% CI, 1.23-4.54), 33% humerus (OR, 2.76; 95% CI, 1.47-5.14); and
      white Asian 20% femur (OR, 1.56; 95% CI, 1.01-2.46), 22% humerus (OR, 1.56; 95%
      CI, 1.01-2.42). CONCLUSION: Genetic sonogram was screen positive more frequently
      because of shorter long bone measurements in all nonwhite ethnicities.

PMID- 19393986
TI  - Role of intraoperative enteroscopy in the management of obscure gastointestinal
      bleeding at the time of video-capsule endoscopy.
AB  - BACKGROUND: This study aimed at evaluating the role of intraoperative enteroscopy
      (IOE) for the management of obscure gastrointestinal (GI) bleeding in patients
      who had been preoperatively explored by video-capsule endoscopy (VCE). METHODS:
      Eighteen patients who underwent IOE for obscure GI bleeding were prospectively
      recorded between November 2000 and January 2007. The bleeding site was
      preoperatively localized by VCE in the small bowel in 15 patients, but the origin
      of bleeding remained unknown in 3 patients. RESULTS: In the 3 patients with
      negative VCE, IOE was normal, but intraoperative conventional endoscopy
      identified gastric (n = 1) and colonic (n = 2) lesions. Among the 15 patients
      with VCE positive for small-bowel lesions, laparotomy and IOE yielded
      localization and treatment (surgical n = 11 and endoscopic n = 2) guidance for 13
      of 15 (87%) lesions. At median 19-month follow-up, 3 bleeding recurrences (3 of
      15 [20%]) were recorded, resulting in a 73% therapeutic efficacy of IOE.
      CONCLUSIONS: IOE remains useful for the management of obscure GI bleeding when
      preoperative VCE is positive for small-bowel lesions that are not reachable by
      nonoperative enteroscopy. When VCE is negative, new conventional endoscopy should
      be proposed instead of IOE.

PMID- 19393988
TI  - Differential regulation of MMP-13 expression in two models of experimentally
      induced periodontal disease in rats.
AB  - OBJECTIVE: Evaluate expression of MMP-13 during the course of two models
      experimentally induced periodontal disease in rats. DESIGN: Expression of MMP-13
      at mRNA and protein levels was studied, respectively, by reverse transcription
      polymerase chain reaction (RT-PCR) and Western blotting. Two experimental models
      were used: LPS injections and ligature placement. 30mug of LPS from Eschericia
      coli was injected twice a week into the palatal aspect of upper molars. Ligatures
      were placed at the gingival margin around lower first molars. Controls received
      injections of PBS vehicle and no ligatures on lower molars. Samples were
      collected 5, 15 and 30 days after initiation of periodontal disease and processed
      for extraction of total RNA, total protein, and routinely processed for
      histology. RESULTS: Both experimental models produced a significant increase on
      the inflammatory infiltrate that paralleled elevated levels of MMP-13 mRNA and
      protein at 5 and 15 days. The LPS model was associated with a sustained level of
      inflammation and increased MMP-13 mRNA throughout the 30 days, whereas the
      ligature model showed a decrease on the severity of inflammation and MMP-13 mRNA
      at the 30-day period. Interestingly, MMP-13 protein levels were diametrically
      contrary to the mRNA levels. CONCLUSION: MMP-13 expression during LPS- and
      ligature-induced experimental periodontal disease follows the increase on
      severity of inflammation at the earliest periods. At 30 days, there is a decrease
      on the severity of inflammation on the ligature model associated with decreased
      MMP-13 mRNA. There is a lack of transcription-translation coupling of MMP-13 gene
      in both experimental models.

PMID- 19393987
TI  - Clinical and microstructural aberrations of enamel of deciduous and permanent
      teeth in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal
      dystrophy.
AB  - OBJECTIVE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      (APECED) causes multiple endocrine deficiencies, oral candidiasis and different
      forms of ectodermal dystrophy including enamel hypoplasia, documented in
      permanent teeth. Our purpose was to examine dental aberrations associated with
      APECED, including possible manifestations in primary teeth. DESIGN: We studied
      clinically, radiographically, and by scanning electron microscopy (SEM) teeth of
      children belonging to two APECED families with different mutations in the AIRE
      gene. RESULTS: In addition to enamel defects in the permanent teeth we observed
      hypoplastic pits and hypomaturated patches in the deciduous teeth with underlying
      changes in the prismatic ultrastructure. The enamel of the permanent molars
      exhibited a layered arrangement with included whirl-like formations. CONCLUSIONS:
      Our findings confirm that APECED causes enamel defects that are individually but
      chronologically distributed, and can alter enamel development early enough to
      affect deciduous teeth.

PMID- 19393989
TI  - Reward processing after catecholamine depletion in unmedicated, remitted subjects
      with major depressive disorder.
AB  - BACKGROUND: We investigated whether performance on a reward processing task
      differs between fully remitted patients with major depressive disorder (MDD) and
      healthy control subjects after catecholamine depletion. METHODS: Seventeen
      unmedicated subjects with remitted MDD (RMDD) and 13 healthy control subjects
      underwent catecholamine depletion with oral alpha-methyl-para-tyrosine (AMPT) in
      a randomized, placebo-controlled, double-blind crossover study. The main outcome
      measure was the reaction time on the monetary incentive delay (MID) task.
      RESULTS: A diagnosis x drug interaction was evident (p = .001), which was
      attributable to an increase in reaction time across all incentive levels after
      AMPT in RMDD subjects (p = .001) but no significant AMPT effect on reaction time
      in control subjects (p = .17). There was no drug x diagnosis interaction on
      control tasks involving working memory or attention. In the RMDD sample the AMPT
      induced depressive symptoms correlated with AMPT-induced changes in reaction time
      at all incentive levels of the MID task (r values = .58-.82, p < .002).
      CONCLUSIONS: Under catecholamine depletion the RMDD subjects were robustly
      differentiated from control subjects by development of performance deficits on a
      reward processing task. These performance deficits correlated directly with the
      return of depressive symptoms after AMPT administration. The sensitivity of
      central reward processing systems to reductions in brain catecholamine levels
      thus seems to represent a trait-like marker in MDD.

PMID- 19393990
TI  - Gene expression patterns associated with posttraumatic stress disorder following
      exposure to the World Trade Center attacks.
AB  - BACKGROUND: Although genetic risk factors for posttraumatic stress disorder
      (PTSD) in similarly traumatized cohorts can be confounded with risk for type of
      exposure, the primary risk for exposure to the 9/11 attack on New York City was
      proximity, allowing study of PTSD risk in a sample that is not confounded by
      exposure-related risk. METHODS: Thirty-five Caucasians (15 with PTSD, stratified
      for exposure, age, and gender) were selected from a population-representative
      sample of persons exposed to the attack from which longitudinal data had been
      collected in four previous waves. Whole blood gene expression and cortisol levels
      were obtained. RESULTS: Seventeen probe sets were differentially expressed in
      PTSD. Identified genes were generally involved in hypothalamic-pituitary-adrenal
      (HPA) axis, signal transduction, or brain and immune cell function. FKBP5, a
      modulator of glucocorticoid receptor (GR) sensitivity, showed reduced expression
      in PTSD, consistent with enhanced GR responsiveness. FKBP5 expression was
      predicted by cortisol when entered with PTSD severity in regression analysis.
      Quantitative polymerase chain reaction confirmed significant reductions in FKBP5.
      Also less expressed in PTSD were STAT5B, a direct inhibitor of GR, and major
      histocompatibility complex (MHC) Class II. CONCLUSIONS: Consistent with
      observations of HPA axis dysfunction in PTSD, several genes involved in
      glucocorticoid signaling are differentially expressed among those with current
      PTSD.

PMID- 19393992
TI  - Impaired semantic inhibition during lexical ambiguity repetition in Parkinson's
      disease.
AB  - Impairments of semantic processing and inhibition have been observed in
      Parkinson's disease (PD), however, the consequences of faulty meaning selection
      and suppression have not been considered in terms of subsequent lexical
      processing. The present study employed a lexical ambiguity repetition paradigm
      where the first presentation of an ambiguity paired with a target biasing its
      dominant or subordinate meaning (e.g., bank - money or bank - river) was followed
      after several intervening trials by a presentation of the same ambiguity paired
      with a different target that biases the same (congruent) or a different
      (incongruent) meaning to that biased on the first presentation. Meaning dominance
      (dominant or subordinate weaker meanings) and interstimulus interval (ISI) were
      manipulated. Analyses conducted on the second presentation indicated priming of
      congruent meanings and no priming for the incongruent meanings at both short and
      long ISIs in the healthy controls, consistent with suppression of meanings
      competing with the representation biased in the first presentation. In contrast,
      the PD group failed to dampen activation for the incongruent meaning at the long
      ISI when the first presentation was subordinate. This pattern is consistent with
      an impairment of meaning suppression which is observed under controlled
      processing conditions and varies as a function of meaning dominance of the first
      presentation. These findings further refine our understanding of lexical-semantic
      impairments in PD and suggest a mechanism that may contribute to discourse
      comprehension impairments in this population.

PMID- 19393993
TI  - Response to: Evidence of an age-related threshold effect of polychlorinated
      biphenyls (PCBs) on neuropsychological functioning in a Native American
      population (Environ. Res. 2009; 109(1):73-85).

PMID- 19393994
TI  - Ectopic pregnancy after hysterectomy: a review and insight into etiology and
      prevention.
AB  - OBJECTIVE: To review all reported cases of ectopic pregnancy after hysterectomy.
      DESIGN: Medline literature search 1966 to Jan 2009. Search terms included
      "ectopic pregnancy," "post hysterectomy ectopic pregnancy," "pregnancy after
      hysterectomy." The bibliography of all retrieved articles was searched for
      additional sources of data. SETTING: Academic medical center. PATIENT(S): Women
      with ectopic pregnancies following hysterectomy. INTERVENTION(S): Surgical
      removal. MAIN OUTCOME MEASURE(S): To review all reported cases of ectopic
      pregnancy after hysterectomy. RESULT(S): Fifty-six cases of ectopic pregnancies
      after hysterectomy have been reported. Thirty-one such cases were diagnosed and
      treated in the immediate period after hysterectomy, "early presentation," and
      were pregnancies presumed to have been present at the time the hysterectomy was
      performed. Twenty-five cases of "late presentation" ectopic pregnancy after
      hysterectomy have been reported, certainly developing as a result of a
      communication between the vagina and the peritoneal cavity. CONCLUSION(S): Every
      woman with intact ovaries, despite previous hysterectomy, who presents with
      abdominal pain, should be screened for pregnancy. "Early presentation" ectopic
      pregnancies can be prevented with adequate contraception before hysterectomy or
      by avoiding operating in the periovulatory or luteal phase of the menstrual
      cycle. "Late presentation" ectopic pregnancies after hysterectomy are likely
      dependent on the type of hysterectomy performed and the presence or a residual
      cervix.

PMID- 19393995
TI  - Coexistence of endometriosis in women with symptomatic leiomyomas.
AB  - OBJECTIVE: To investigate the coexistence of endometriosis in women presenting
      with symptomatic leiomyomas. DESIGN: Retrospective study. SETTING: Tertiary
      university medical center. PATIENT(S): We reviewed the medical records of 131
      patients who underwent laparoscopic myomectomy or hysterectomy. All patients were
      consented for possible concomitant diagnosis and treatment of endometriosis.
      INTERVENTION(S): All patients underwent laparoscopic myomectomy or hysterectomy.
      MAIN OUTCOME MEASURE(S): The main outcome measure of the study was the presence
      or absence of endometriosis. RESULT(S): Of the 131 patients, 113 were diagnosed
      with endometriosis and fibroids, while 18 were diagnosed with fibroids alone.
      Patients with fibroids were on average 4.0 years older than those with
      endometriosis and fibroids (41 vs. 45). Patients with both diagnoses were also
      more likely to present with pelvic pain and nulliparity than those with fibroids
      alone. CONCLUSION(S): An overwhelming majority of patients with symptomatic
      fibroids were also diagnosed with endometriosis. Overlooking the concomitant
      diagnosis of endometriosis in these women may lead to suboptimal treatment of the
      patients. Further studies are needed to evaluate the impact of surgical
      treatments on symptom resolution.

PMID- 19393996
TI  - The impact on ovarian reserve after laparoscopic ovarian cystectomy versus three
      stage management in patients with endometriomas: a prospective randomized study.
AB  - OBJECTIVE: To investigate the effect of two different laparoscopic methods on
      ovarian reserve in patients with ovarian endometriomas. DESIGN: Prospective,
      randomized clinical trial. SETTING: Endoscopy unit of a university hospital.
      PATIENT(S): Twenty women with endometriomas. INTERVENTION(S): Patients were
      randomly selected to undergo either laparoscopic cystectomy for endometrioma
      (group 1) or the "three-step procedure" (group 2). Before and 6 months after
      laparoscopy all patients were evaluated, and 12 months postoperatively they
      underwent ultrasound scan examination. MAIN OUTCOME MEASURE(S): The primary end
      point was ovarian reserve damage based on the alterations of anti-Mullerian
      hormone (AMH). Secondary end points were the changes of antral follicle count and
      serum concentration of FSH, LH, E(2), and inhibin B. RESULT(S): Mean serum AMH
      was reduced significantly from 3.9-2.9 ng/mL in group 1 compared with the
      reduction from 4.5-3.99 ng/mL in group 2. CONCLUSION(S): Ovarian reserve
      determined by AMH is less diminished after the three-step procedure compared with
      cystectomy of endometriomas.

PMID- 19393997
TI  - Artificial oocyte activation and intracytoplasmic sperm injection.
AB  - OBJECTIVE: To review different methods for artificial oocyte activation and its
      impact on intracytoplasmic sperm injection (ICSI). DESIGN: Literature review.
      SETTING: University-based and university-affiliated medical centers. PATIENT(S):
      None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): The ICSI
      procedure improves fertilization rates in cases of male factor infertility;
      however, fertilization failure still occurs in 2% to 3% of ICSI cycles. The main
      cause of failed fertilization is failure to complete oocyte activation. The
      investigators do not use a variety of mechanical, electrical, and chemical
      methods to mimic the calcium rise necessary to activate oocytes after ICSI.
      Chemical activation is the most commonly used method for artificial oocyte
      activation, resulting in high fertilization rates. CONCLUSION(S): Artificial
      oocyte activation (AOA) may be useful in selected patients who have low
      fertilization potential. Further studies are required to establish the biosafety
      of AOA, and clinical tests are needed to evaluate the activation potential of
      semen samples for proper patient selection.

PMID- 19393998
TI  - Oocyte retrieval versus conversion to intrauterine insemination in patients with
      poor response to gonadotropin therapy.
AB  - We compared cycle characteristics and outcomes for planned in vitro fertilization
      cycles with five or fewer developing follicles that proceeded to retrieval (n =
      170) with those that converted to intrauterine insemination (IUI) (n = 50). The
      risk of no embryo transfer was 24% in cycles that proceeded to retrieval. Live
      birth rate per cycle started was similar for IUI (6%) compared with retrieval
      (7%).

PMID- 19393999
TI  - "Physiologic ICSI": hyaluronic acid (HA) favors selection of spermatozoa without
      DNA fragmentation and with normal nucleus, resulting in improvement of embryo
      quality.
AB  - OBJECTIVE: To evaluate the role of hyaluronic acid (HA) for sperm selection
      before intracytoplasmic sperm injection (ICSI). DESIGN: Three prospective
      studies. SETTING: Private assisted reproduction center in Italy. PATIENT(S):
      Study 1: 20 men. Study 2: 15 men. Study 3: 206 couples treated with ICSI on a
      limited number of oocytes per patient (1-3) in accordance with Italian IVF law.
      INTERVENTION(S): Study 1: determination of sperm DNA fragmentation of HA-bound
      spermatozoa versus spermatozoa in polyvinylpyrrolidone (PVP). Study 2: assessment
      of nuclear morphology of HA-bound spermatozoa versus spermatozoa in PVP. Study 3:
      randomized study comparing conventional PVP-ICSI to ICSI in which the spermatozoa
      are selected for their capacity to bind to HA (HA-ICSI). MAIN OUTCOME MEASURE(S):
      Study 1: sperm DNA fragmentation rate. Study 2: sperm nucleus normalcy rate
      according to motile sperm organellar morphology examination criteria. Study 3:
      fertilization, embryo quality and development, and implantation and pregnancy.
      RESULT(S): Spematozoa bound to HA show a significant reduction in DNA
      fragmentation (study 1) and a significant improvement in nucleus normalcy (study
      2) compared with spermatozoa immersed in PVP. Furthermore, injection of HA-bound
      spermatozoa (HA-ICSI) significantly improves embryo quality and development
      (study 3). CONCLUSION(S): Hyaluronic acid may optimize ICSI outcome by favoring
      selection of spermatozoa without DNA fragmentation and with normal nucleus.
      Furthermore, HA may also be used to speed up the selection of spermatozoa with
      normal nucleus during intracytoplasmic morphologically selected sperm injection
      (IMSI).

PMID- 19394000
TI  - Ovarian and adipose tissue dysfunction in polycystic ovary syndrome: report of
      the 4th special scientific meeting of the Androgen Excess and PCOS Society.
AB  - Significant advances have been made in our understanding of ovarian dysfunction
      in polycystic ovary syndrome (PCOS), and alterations in adipose tissue function
      are likely to play an important role in its pathophysiology. This review
      highlights the principal novel concepts presented at the 4th special scientific
      meeting of the Androgen Excess and PCOS Society, "Ovarian and Adipose Tissue
      Dysfunction: Potential Roles in Polycystic Ovary Syndrome," which occurred on
      June 6, 2008 in San Francisco, California.

PMID- 19394001
TI  - Serum estradiol levels during controlled ovarian hyperstimulation influence the
      pregnancy outcome of in vitro fertilization in a concentration-dependent manner.
AB  - OBJECTIVE: To determine an optimal serum E(2) level on the day of hCG
      administration in controlled ovarian hyperstimulation (COH) during IVF-ET without
      compromising pregnancy outcome. DESIGN: Retrospective study. SETTING: Large urban
      medical center. PATIENT(S): Data of 455 cycles of fresh IVF-ET with COH.
      INTERVENTION(S): Serum E(2) levels on the day of hCG administration were
      categorized into five groups: group A (<1000 pg/mL), group B (1000-2000 pg/mL),
      group C (2000-3000 pg/mL), group D (3000-4000 pg/mL), and group E (>4000 pg/mL).
      MAIN OUTCOME MEASURE(S): Serum E(2) levels, number of oocytes retrieved,
      pregnancy outcomes. RESULT(S): Of 455 cycles, 148 (32.5%) cycles resulted in
      clinical pregnancy. The implantation rate was 12.2%, and the delivery rate was
      18.7%. The number of oocytes obtained increased with increasing serum E(2)
      levels. The pregnancy rate gradually increased from group A to D as E(2) levels
      increased but decreased in group E. In women <38 years, the IVF-ET outcomes were
      similar to those of total patients. However, in women >/=38 years old, pregnancy
      and delivery rates were higher in group C than in other groups. CONCLUSION(S):
      These results show that serum E(2) levels have a concentration-dependent effect
      on the pregnancy outcome, suggesting an optimal range of E(2) level for achieving
      a successful pregnancy. This optimal range of serum E(2) level in women is age
      dependent: 3000-4000 pg/mL for women <38 years and 2000-3000 pg/mL for women
      >/=38 years.

PMID- 19394002
TI  - A prospective randomized placebo-controlled study of the effect of acupuncture in
      infertile patients with severe oligoasthenozoospermia.
AB  - In this first prospective, randomized, single-blind, placebo-controlled study, 28
      infertile patients with severe oligoasthenozoospermia received acupuncture
      according to the principles of traditional Chinese medicine (TCM) and 29
      infertile patients received placebo acupuncture. A significantly higher
      percentage of motile sperm (World Health Organization categories A-C), but no
      effect on sperm concentration, was found after acupuncture compared with placebo
      acupuncture.

PMID- 19394003
TI  - Smoking is associated with increased free testosterone and fasting insulin levels
      in women with polycystic ovary syndrome, resulting in aggravated insulin
      resistance.
AB  - OBJECTIVE: To evaluate the impact of smoking on endocrine, metabolic, and
      clinical parameters in women with polycystic ovary syndrome (PCOS). DESIGN:
      Cohort analysis. SETTING: University hospital. PATIENT(S): 346 women with PCOS,
      including 98 smokers and 248 nonsmokers. INTERVENTION(S): Screening panel,
      including physical examination, weight and height measurement, and ultrasound
      examination of the ovaries, and hormone and insulin measurements. MAIN OUTCOME
      MEASURE(S): Clinical, metabolic, and endocrine parameters, oral glucose tolerance
      test, calculation of insulin resistance indexes. RESULT(S): In women with PCOS,
      smoking was associated with statistically significantly increased levels of
      fasting insulin and calculated free testosterone (cFT) and with a raised free
      androgen index (FAI) score, which resulted in aggravated scores on the
      homeostatic model for assessment of insulin resistance (HOMA-IR). However, no
      differences were observed between the smoking and nonsmoking groups with regard
      to the clinical parameters for hirsutism, acne, ovulatory function (classified as
      eumenorrhea, oligomenorrhea, and amenorrhea), or polycystic ovaries using the
      ultrasound criteria recommended according to the Rotterdam definition.
      CONCLUSION(S): In women with PCOS, smoking is associated with increased free
      testosterone and fasting insulin levels, resulting in aggravated insulin
      resistance. However, there were no differences between smokers and nonsmokers
      when clinical parameters were compared.

PMID- 19394004
TI  - Deep sedation with propofol does not precipitate hepatic encephalopathy during
      elective upper endoscopy.
AB  - BACKGROUND: The risk of hepatic encephalopathy (HE) precipitated by propofol has
      not been established. OBJECTIVE: To know whether the use of propofol for
      endoscopy in patients with cirrhosis induces minimal or overt HE. DESIGN: A
      cohort study. SETTING: A tertiary-referral university hospital endoscopy unit.
      PATIENTS: Patients with cirrhosis who received an endoscopy with propofol
      sedation. We excluded patients with clinical HE. A group of patients without
      liver disease was included to compare the incidence of adverse effects.
      INTERVENTIONS: Minimal HE (MHE) was diagnosed by using the psychometric hepatic
      encephalopathy score (PHES) battery of psychometric tests. Cognitive status
      before and 1 hour after the endoscopy was evaluated by measuring the critical
      flicker frequency (CFF). MAIN OUTCOME MEASUREMENTS: Overt and minimal HE.
      RESULTS: Twenty patients with cirrhosis and 20 patients without cirrhosis were
      included. There were no differences between groups in the incidence of adverse
      effects. Thirteen patients (65%) had MHE before the endoscopy. No patient
      developed overt HE after sedation. We did not observe differences in CFF before
      and after sedation in patients without MHE: median (25th-75th percentile), 40.8
      Hz (37.1-46.0 Hz) versus 41.1 Hz (36.0-44.3 Hz), P = .8). None of the patients
      who were without MHE showed a decrease in the CFF under the cutoff of 39 Hz after
      sedation. There were not significant changes in CFF before and after propofol
      sedation in patients previously diagnosed of MHE: median (25th-75th percentile),
      40.6 Hz (36.8-49.1 Hz) versus 42.7 Hz (36.8-52.4 Hz), P = .08. LIMITATION: A
      small number of patients were included in the study. CONCLUSIONS: The use of
      propofol in the sedation of patients with cirrhosis during endoscopic procedures
      does not precipitate minimal or overt HE.

PMID- 19394005
TI  - EUS-guided diagnosis and successful endoscopic transpapillary management of an
      intrahepatic pancreatic pseudocyst masquerading as a metastatic pancreatic
      adenocarcinoma (with videos).

PMID- 19394006
TI  - EUS-guided sampling of suspected GI stromal tumors.
AB  - BACKGROUND: The diagnostic yield of EUS-guided FNA (EUS-FNA) of suspected GI
      stromal tumors (GIST) has not been assessed in large series. OBJECTIVE: Our
      purpose was to determine the diagnostic yield of EUS-FNA of subepithelial lesions
      with EUS features suggestive of GIST. DESIGN: Retrospective database review.
      SETTING: Tertiary care referral center and an urban Veterans Administration
      hospital. PATIENTS: Consecutive patients referred for EUS evaluation of upper GI
      subepithelial lesions of the fourth endosonographic layer who underwent EUS-FNA.
      MAIN OUTCOME MEASUREMENTS: Proportion of patients whose cytopathologic
      examination was diagnostic (immunohistochemical stains establish a specific
      diagnosis), suspicious (spindle cells identified, quantity not sufficient for
      specific stains), or nondiagnostic. RESULTS: A total of 112 patients (45.5%
      female, mean age 61.6 years) underwent EUS-FNA (mean number of FNA passes 5.3).
      Tumor location was as follows: stomach 62.5%, esophagus 30.4%, and duodenum 7.1%.
      EUS-FNA was diagnostic in 61.6%, suspicious (spindle cells) in 22.3%, and
      nondiagnostic in 16.1%. The histologic results were 31.3% GIST, 26.8% leiomyomas,
      22.3% spindle cell neoplasms, 3.5 % neural tumors, and 16.1% nondiagnostic.
      Fifteen (12.5%) patients also underwent EUS-guided core needle biopsy needle
      sampling; 7 were diagnostic, 2 suspicious, and 6 nondiagnostic. Twenty-four
      (20.0%) patients underwent jumbo forceps sampling; 5 were diagnostic, 1
      suspicious, and 18 nondiagnostic. There were no cases of diagnostic core needle
      biopsy after nondiagnostic FNA core needle biopsy. Jumbo forceps biopsy of
      ulcerated masses was diagnostic in 3 GISTs in which FNA was nondiagnostic.
      Univariate and multivariate analyses showed that no variable was associated with
      an increased diagnostic yield. CONCLUSIONS: EUS-FNA sampling of subepithelial
      lesions was diagnostic in 61.6% and showed a spindle cell neoplasm ("suspicious")
      in another 22.3% (diagnostic yield 83.9%). Core needle biopsy needle sampling did
      not increase the yield, but in the setting of an ulcerated mass, forceps biopsy
      may be diagnostic.

PMID- 19394007
TI  - Omentoplasty for gastrotomy closure after natural orifice transluminal endoscopic
      surgery procedures (with video).
AB  - INTRODUCTION: The utility of the greater omentum has not been assessed in
      transluminal access closure after natural orifice transluminal endoscopic surgery
      (NOTES) procedures. OBJECTIVE: Our purpose was to evaluate the feasibility,
      efficacy, and safety of omentoplasty for gastrotomy closure. METHODS AND
      PROCEDURES: Survival experiments in 9 female 40-kg pigs were randomly assigned to
      3 groups: group A, endoscopic full-thickness resection (EFTR) for transgastric
      access and peritoneoscopy without closure; group B, ETFR and peritoneoscopy with
      omentoplasty (flap of omentum is pulled into the stomach and attached to the
      gastric mucosa with clips but no clips are used for gastrotomy closure itself);
      group C, balloon dilation for opening and peritoneoscopy followed by omentoplasty
      for closure. The animals were observed for 2 weeks and then underwent endoscopy
      and necropsy with histologic evaluation. RESULTS: Transgastric opening and
      peritoneoscopy were achieved in all pigs. In groups B and C, a flap of omentum
      was easily placed to seal the gastrotomy and then attached to the gastric mucosa
      with 2 to 5 clips (median 4) in 7 to 20 minutes (median 15 minutes). In group A,
      peritonitis developed in all animals. In both groups B and C, all animals
      survived 15 days with no peritonitis and minimal adhesions outside the gastrotomy
      site. In addition, all achieved complete healing (transmural, n = 4; mucosal
      ulceration, n = 2) of the gastrotomy site. One animal in group B had an 18-mm
      abscess in the omental flap. LIMITATIONS: Animal model, small sample size, lack
      of appropriate controls for group C. CONCLUSIONS: Omentoplasty of the gastrotomy
      site is a technically feasible method to seal balloon-created transgastric access
      to the peritoneal cavity after NOTES procedures.

PMID- 19394008
TI  - Evaluation of a manually driven, multitasking platform for complex endoluminal
      and natural orifice transluminal endoscopic surgery applications (with video).
AB  - BACKGROUND: The Direct Drive Endoscopic System (DDES) is a multitasking platform
      developed to overcome the limitations of the currently available rigid and
      flexible endoscopic systems in application to natural orifice transluminal
      endoscopic surgery (NOTES), single-port laparoscopy, and advanced endoluminal
      procedures. The system consists of a 3-channel, steerable guide sheath accepting
      a 6-mm endoscope and two 4-mm articulating instruments. The system's overall
      design enables the interventionalist to operate instruments bimanually from a
      stable platform, conveying a laparoscopic paradigm to the functional working
      space at the distal end of the flexible guide sheath. OBJECTIVE: To assess the
      basic functionality of the DDES device in a series of defined exercises by using
      ex vivo porcine stomachs and 1 in vivo animal model. DESIGN: Ex vivo calibration
      and training exercises, including EMR, full-thickness suturing, and knot tying.
      SETTING: Animal laboratory. INTERVENTIONS: EMR, full-thickness suturing, and knot
      tying. MAIN OUTCOME MEASUREMENTS: Successful completion of specified tasks.
      RESULTS: Independent instrument movement with a wide range of motion allowed the
      interventionalist to perform several complex tasks efficiently. The DDES was able
      to (1) grasp tissue and hold it under tension, (2) cut through layers of porcine
      stomach in a controlled fashion, (3) suture, and (4) tie knots. LIMITATION: Ex
      vivo study. CONCLUSIONS: This novel multitasking platform demonstrated surgical
      functionality including triangulation, cutting, grasping, suturing, and knot
      tying. Preliminary results suggest that the DDES can perform complex endosurgical
      tasks that have traditionally been challenging or impossible with the standard
      endoscopic paradigm, and may enable NOTES, single-port laparoscopy, and complex
      endoluminal procedures.

PMID- 19394009
TI  - Identification of predictive factors for early neoplasia in Barrett's esophagus
      after autofluorescence imaging: a stepwise multicenter structured assessment.
AB  - BACKGROUND: Autofluorescence imaging is a novel imaging technique that may
      improve the detection of early neoplasia in Barrett's esophagus. Autofluorescence
      imaging is, however, associated with a 40% to 81% false-positive rate. OBJECTIVE:
      Our purpose was to identify endoscopic features that may predict the presence of
      early neoplasia in autofluorescence-positive areas. DESIGN: Descriptive and
      prospective cohort study. SETTING: Tertiary referral centers for the detection
      and treatment of early Barrett's neoplasia. PATIENTS AND METHODS: Patients
      undergoing autofluorescence endoscopy. High-quality images with autofluorescence
      imaging and white-light endoscopy were obtained with corresponding histologic
      study. A systematic image evaluation process was performed, including an
      unblinded orientation phase (10 areas), a blinded derivation phase, and a blinded
      validation phase by 5 international experts in autofluorescence imaging (80
      areas). Subsequently the identified features were validated in a prospective
      pilot study. MAIN OUTCOME MEASUREMENTS: Association between endoscopic features
      and presence of early neoplasia in autofluorescence-positive areas. RESULTS:
      Autofluorescence intensity, proximity of gastric folds <1 cm, and different
      appearance on white-light endoscopy were independently associated with early
      neoplasia in autofluorescence-positive areas on multivariate analysis. The kappa
      values for interobserver agreement of these factors were moderate, ranging
      between 0.49 to 0.56. The association with autofluorescence intensity and
      different appearance on white-light endoscopy was confirmed in a prospective
      pilot study. LIMITATION: Selected set of images from a high-risk population
      (tertiary referral center). CONCLUSION: We found specific endoscopic features
      that were associated with early neoplasia in autofluorescence-positive areas.
      These findings can be used in future prospective studies to improve the accuracy
      of autofluorescence imaging without performing magnification endoscopy for
      detailed inspection of suspicious areas.

PMID- 19394010
TI  - Intraductal balloon-guided direct peroral cholangioscopy with an ultraslim upper
      endoscope (with videos).
AB  - BACKGROUND: Peroral cholangioscopy (POC) provides direct visualization of the
      bile duct and facilitates diagnostic procedures and therapeutic intervention. The
      currently available mother-baby endoscope system is not widely used because of
      several limitations. Although direct cholangioscopy with an ultraslim upper
      endoscope with a guidewire has been reported, success is not always guaranteed.
      OBJECTIVE: To evaluate the feasibility and success rate of direct POC using an
      ultraslim endoscope with an intraductal balloon to maintain access compared with
      the guidewire method. DESIGN: Prospective, observational clinical feasibility
      study. SETTING: Tertiary referral center. MAIN OUTCOME MEASUREMENTS: We compared
      overall procedure success rates and complications. A successful procedure was
      defined as one in which the endoscope was advanced into the bifurcation or
      stenotic segment of the biliary system. PATIENTS AND METHODS: Twenty-nine
      patients with biliary disease underwent direct POC. All patients had previously
      undergone an endoscopic sphincterotomy or papillary balloon dilation with a large
      balloon. Eleven patients underwent wire-guided direct POC. Intraductal balloon
      guided direct POC was performed in 21 patients. The balloon catheter was used to
      maintain access while an ultraslim upper endoscope was advanced over the balloon
      catheter, through the ampulla of Vater, and directly into the bile duct. RESULTS:
      Wire-guided direct POC was successful in 5 of 11 (45.5%) patients. In contrast,
      the success rate of intraductal balloon-guided direct POC was 95.2% (20/21
      patients, P < .05). Forceps biopsies under direct visualization of the
      intraductal lesion and therapeutic intervention, including laser lithotripsy or
      electrohydraulic lithotripsy, were performed successfully. Procedure-related
      complications were not observed. LIMITATIONS: A small number of patients and no
      comparison with conventional cholangioscopy. CONCLUSIONS: Intraductal balloon
      guided direct POC with an ultraslim upper endoscope allows the direct visual
      examination and therapeutic intervention of bile ducts in patients with biliary
      disease. Further development of the endoscopic apparatus and specialized
      accessories are expected to facilitate this procedure.

PMID- 19394011
TI  - Endoscopic versus surgical therapy for early cancer in Barrett's esophagus: a
      decision analysis.
AB  - BACKGROUND: Esophagectomy for early esophageal adenocarcinoma is associated with
      increased operative mortality and morbidity, but possibly a decreased recurrence
      rate compared with endoscopic therapy when using EMR and radiofrequency ablation.
      OBJECTIVE: To compare the cost-effectiveness of esophagectomy and endoscopic
      therapy in the treatment of early esophageal adenocarcinoma. DESIGN: Decision
      analysis model. MAIN OUTCOME MEASUREMENTS: Incremental cost-effectiveness ratio.
      RESULTS: During the 5-year study period, endoscopic therapy cost $17,000.00 and
      yielded 4.88 quality-adjusted life years, compared with $28,000.00 and 4.59,
      respectively, for esophagectomy. Varying the recurrence rates of cancer or
      Barrett's esophagus metaplasia after endoscopic therapy did not change the
      overall outcome. The sensitivity analysis demonstrated, however, that the outcome
      depended on the rate of lymph node involvement and operative mortality. Under the
      best of circumstances in favor of esophagectomy, such as 2% operative mortality,
      no reduced quality of life after esophagectomy, and a low 5-year survival rate
      after recurrence of endoscopic ablation, the risk of positive lymph nodes still
      needed to exceed 25% before esophagectomy became the preferred treatment option.
      This threshold is twice as high as the values reported for early submucosal
      cancer invasion. LIMITATIONS: Limited data are available about the long-term
      outcome of EMR and radiofrequency ablation. CONCLUSIONS: Endoscopic therapy for
      early Barrett's esophagus adenocarcinoma is more effective and less expensive
      than esophagectomy. Even in early esophageal adenocarcinoma with submucosal
      invasion, endoscopic therapy is a cost-effective alternative to esophagectomy,
      especially in patients with a high operative risk.

PMID- 19394013
TI  - Total elbow arthroplasty for the treatment of insufficient distal humeral
      fractures. A retrospective clinical study and review of the literature.
AB  - Treatment of complex distal humeral fractures in older patients with osteopenic
      bone remains a major surgical challenge. We report the results of 11 patients
      over 75 years of age who underwent semiconstrained sloppy-hinge total elbow
      arthroplasty (TEA) due to comminuted intraarticular fractures of the distal
      humerus. There were 9 women and 2 men with a mean age of 79.6 years. The mean
      duration of follow up was 2.8 years. According to AO classification, there were 8
      type C3 and 3 type C2 fractures. The mean time from injury to operation was 4.3
      days and the mean length of hospital stay was 9.8 days. The elbow
      flexion/extension and forearm pronation/supination arc of motion averaged 107(0)
      and 121(0) respectively. The mean Mayo Elbow Performance Score (MEPS) was 90
      points, equivalent to excellent result. One patient sustained a periprosthetic
      humeral fracture and signs of non-progressive radiolucency were found in 8 out of
      the 11 elbows. Our search in the English and International literature revealed 9
      other clinical studies describing the results of TEA in 167 patients with 168
      distal humeral fractures. The mean age of patients varied from 69 to 84.6 years
      and the mean follow up from 17.8 months to 7 years. The mean MEPS among the
      studies was between 85 and 95 points. Wound infection was diagnosed in 9 cases
      (5.4%) but component removal and subsequent reimplantation was only applied in 3
      elbows (1.8%). Partial ulnar nerve lesions were reported in 11 patients (6.5%)
      and reflex sympathetic dystrophy was developed in 5 patients (3%). In 3 elbows
      (1.8%) a periprosthetic fracture after a fall was recorded. Radiolucent lines
      between the cement mantle and bone interface were described in 24 cases (14.3%)
      but the majority of them (17 cases) were stable and asymptomatic. In conclusion,
      TEA constitutes a viable treatment option for the complex distal humeral
      fractures in elderly and medically compromised patients. Careful patient
      selection and regular follow up evaluation are mandatory for achieving an optimal
      result and eliminating the risks of mismanagement and early implant failure.

PMID- 19394012
TI  - EUS-guided FNA of solid pancreatic masses: high yield of 2 passes with combined
      histologic-cytologic analysis.
AB  - BACKGROUND: EUS-guided FNA (EUS-FNA) is an established tissue-acquisition
      technique, with most studies concentrating on cytologic analyses of specimens,
      with only few data existing on histologic assessment. OBJECTIVE: To assess the
      sensitivity of a combined analysis of histologic followed by cytologic tissue
      diagnosis. DESIGN: A retrospective 3-center study. METHODS: In consecutive
      patients undergoing FNA of solid pancreatic masses, core specimens were harvested
      for histology; residual tissue was examined cytologically. Only unequivocally
      positive results were regarded as malignant. Criterion standards were positive
      results from EUS-FNA or other histologic findings, or, if negative, clinical
      follow-up data (minimum 12 months). RESULTS: Among 192 patients (110 men; mean
      age 63 years) with mostly pancreatic-head masses (72.4%), overall, adequate
      tissue was obtained in 98.9% of all cases, with a mean of 1.88 needle passes and
      an overall sensitivity of 82.9% (95% CI, 76.0%-88.5%). Histology and subsequent
      cytology provided adequate tissue and sensitivities of 86.5% and 60%, and 92.7%
      and 68.1%, respectively. Excluding cases with inadequate specimens, sensitivities
      rose by 4% to 10%. Histology showed a trend for superiority over cytology only in
      characterizing nonadenocarcinoma tumor types. No differences in sensitivity were
      found between the centers involved. LIMITATIONS: Retrospective design, different
      processing of cytologic specimens. CONCLUSIONS: At EUS-FNA in pancreatic masses,
      combined histologic-cytologic analysis achieved a sensitivity of more than 80%,
      despite a low number of needle passes and may thus save time. Histology alone did
      not reach higher sensitivity than cytology. In particular situations, eg, rare
      tumors, histology may still be required.

PMID- 19394014
TI  - Olecranon fracture fixation with a new implant: biomechanical and clinical
      considerations.
AB  - This study aims to describe the first clinical results in the treatment of
      dislocated olecranon fractures with 2.2-mm, fine-threaded wires with a washer.
      Furthermore, in the second part of the article, the stability of these new
      implants has been compared to standard tension band wiring in a sawbone model.
      PATIENTS: The radiological and clinical outcomes in 24 patients (mean age: 53.6
      years) with 24 isolated Mayo type I and II fractures of the olecranon were
      evaluated in a prospective study after open reduction and internal fixation
      (ORIF) with a new fixation device (FFS; Orthofix). The quality of reduction with
      the implementation of 24 FFS constructions was compared with 24 tension band
      wiring procedures performed by six different surgeons in a standard sawbone Mayo
      type IIa fracture model. Stability was tested in all constructs using a single
      cycle load to failure protocol (group I), cyclic loading for 300 cycles between
      10 and 500 N (group II) and incremental sinusoidal loading from 10 to 200 N with
      an incremental increase of 10 N per cycle (group III) in a laboratory study.
      RESULTS: The Morrey elbow score was excellent in 23 patients and good in one
      patient, with mean DASH score of 1.6. No implant migration, secondary dislocation
      or nonunion was observed. In the sawbone model, the quality of reduction was the
      same with the FFS implants compared to the tension band wiring in the sawbone
      model. Here, bending moments in all three groups showed no significant
      difference, whereas displacement at failure was significantly greater in the
      tension band-wiring group at a single cycle load (p=0.017). CONCLUSION: Clinical
      results were comparable to tension band wiring and stability of the implants in
      the sawbone model was the same; thus, we conclude that the FFS technique can
      serve as an alternative treatment option for isolated olecranon fractures.

PMID- 19394015
TI  - Bone bruising of the distal forearm and wrist in children.
AB  - Bone bruising represents a new category of bone injury that can only be
      demonstrated by magnetic resonance imaging (MRI) with fat suppression. This study
      proposed the nature of non-radiographically evident injuries of the distal radius
      and wrist in children whose symptoms did not resolve after 5 weeks. We aimed to
      describe and classify the lesions and delineate the importance and potential
      complications of the injuries. Bone bruising was diagnosed in 20 patients (mean
      age: 11.6 years; range: 9-13 years). Bone bruises were classified according to
      anatomical location and whether they were solitary lesions or were combined with
      other injuries. Injuries of the distal radius were classified according to
      location: type 1 was localised to the metaphysis, close to the physeal plate;
      type 2 involved both the metaphysis and diaphysis; and type 3 extended on both
      sides of the distal radial growth plate. The type 1 injuries were consistent with
      complete, un-displaced Salter-Harris type I fractures, whilst type 3 lesions were
      potentially Salter-Harris type V injuries. Our data indicate that an MRI should
      be considered for a child with an injury to the distal radius or wrist whose
      symptoms do not resolve after 5 weeks of immobilisation.

PMID- 19394016
TI  - Impact on trauma patient management of installing a computed tomography scanner
      in the emergency department.
AB  - BACKGROUND: Computed tomography (CT) plays a central diagnostic role for trauma
      patients. A 16-slice multi-detector CT scanner was installed in the emergency
      department (ED) of Prince of Wales Hospital in December 2004. The aims of this
      study were to evaluate the impact of the CT scanner within the ED on trauma
      management and to compare the utilisation patterns of trauma CT before and after
      the introduction of EDCT. METHODS: Analysis of prospectively collected trauma
      registry data. All consecutive trauma cases admitted through the ED that
      underwent CT between June 2004 and June 2005 (6 months before and after EDCT
      installation) were included. A positive CT was defined as the identification (by
      a specialist radiologist) of a significant finding which was consistent with
      injury. RESULTS: There were 226 and 202 trauma patients in the 6 months before
      and after EDCT installation, respectively. 111 (49.1%) patients underwent CT
      scanning before EDCT compared with 110 (54.5%) afterwards. 72 (65%) patients had
      CT scans performed before admission to definitive care compared with 99 (90%)
      after EDCT installed (p<0.0001, chi(2) test). Mean time from arrival to first CT
      was shorter after EDCT (102 min vs. 197 min, p=0.011). Mean trauma room length of
      stay increased after EDCT was implemented (106 min vs. 80 min; p<0.001). Median
      time to urgent operation (<6h) was less with EDCT (134 min before vs. 112 min
      after). No changes in median time to neurosurgical operation (138 min before vs.
      148 min after); mean length of stay (12.8 days before vs. 12.5 days after); or
      mortality (8 patients before vs. 7 patients after). There were 203 scans
      (1.8/patient) done before EDCT compared with 226 scans (2.5/patient) after. There
      was no difference in the number of scans done by body region or the proportion of
      positive scans (32% before vs. 30% after). Logistic regression confirmed that
      after adjusting for injury severity and admission physiology, time to first CT
      was shorter (p=0.0307) but ED length of stay was increased (p<0.0001).
      CONCLUSION: After the installation of EDCT, more trauma patients had CT scanning
      before definitive care, and scans were done sooner, with no significant increase
      in the number of unnecessary scans.

PMID- 19394017
TI  - Comparison of three established measures of fear of falling in community-dwelling
      older adults: psychometric testing.
AB  - BACKGROUND: Several approaches have emerged for measuring self-reported fear of
      falling. A comparison of measurement scales' psychometric properties is needed
      for researchers to choose the proper scale for their study. OBJECTIVES: To
      compare the psychometric properties of the Falling Efficacy Scale (FES), the
      Activities-Specific Balance Confidence Scale (ABC) and the Geriatric Fear of
      Falling Measurement (GFFM). DESIGN: Secondary analysis using baseline and 8-week
      data from a randomized, controlled trial on fall and fear of falling prevention.
      SETTINGS: Rural area northeast of Taiwan with assessments conducted in
      participants' homes. PARTICIPANTS: Population-based sample of 168 community
      dwelling older adults aged 60 and older. METHODS: During a home visit, a nurse
      administered the Tinetti Mobility Scale, and asked about the FES, ABC, GFFM,
      WHOQOL, falls, chronic illnesses and medicines taken. RESULTS: Baseline internal
      consistency measured using Cronbach's alpha was 0.98 for the FES, 0.96 for the
      ABC and 0.88 for the GFFM. Baseline concurrent validity between the FES, ABC and
      GFFM measured using a correlation coefficient was 0.88 (FES vs. ABC), -0.55 (FES
      vs. GFFM), and -0.57 (ABC vs. GFFM), respectively, p<.001. All three instruments
      scores were significantly correlated at baseline with physical performance tests
      and WHOQOL. The GFFM demonstrated responsiveness to change at 8 weeks.
      CONCLUSIONS: The FES, ABC and GFFM demonstrated strong internal consistency
      reliability. The GFFM had stronger associations with physical and psychosocial
      functioning and may be more appropriate for studies focused on improving all
      aspects of fear of falling. Both FES and ABC instruments demonstrated ceiling
      effects, which may explain the lack of responsiveness to change in relatively non
      frail older community-dwelling adults. Instruments sensitive to measuring lower
      levels of fear of falling are needed to capture the full range of this phenomenon
      in this population.

PMID- 19394018
TI  - A review of interventions used to improve adherence to medication in older
      people.
AB  - BACKGROUND: Medication mismanagement is a continuous problem particularly in
      older people. Numerous interventions have been developed and tested in an attempt
      to improve adherence with medication in this client group. OBJECTIVES: This
      review aimed to examine the simple to complex interventions that have been used
      to assess and improve adherence with medication in older people. DESIGN: An
      extensive review of the literature was performed and 20 relevant research papers
      and one report were chosen. FINDINGS: Research papers were evaluated according to
      design, RCTs were analysed using the JADAD scoring system, systematic reviews and
      reviews of the literature were reviewed using the Critical Appraisal Skills
      Programme and subjected to a narrative analysis. This process assisted the
      development to emerging themes. Four themes were developed: patient barriers,
      health professional involvement, and health related outcomes and formation
      giving. CONCLUSIONS: The salient findings of the review infer that there is no
      clear definition of non-adherent behaviour. Quantitative interventions fail to
      assess patient choice in relation to medication taking. Pharmacist-driven
      interventions are resource intensive. Health care outcomes and clinical
      effectiveness are seldom addressed in interventions. Among the many difficulties
      encountered when attempting to use interventions to promote adherence with
      medication in older people is their perceptions and beliefs, the appropriateness
      of the medicines prescribed as well as the impact of lifestyle patterns: smoking,
      alcohol and diet. Many intervention studies are of poor quality and do not
      include a theoretical framework to underpin the interventions being used. More
      focused research is needed to improve understanding of the theoretical knowledge
      that underpins the complexities of adherence with medication in older people. In
      depth qualitative studies can be used to develop such theory. In addition, the
      quality of intervention research can be improved by the inclusion of a research
      framework such as the Medical Research Council model.

PMID- 19394019
TI  - Systematic error in mechanical measures of damage during four-point bending
      fatigue of cortical bone.
AB  - Accumulation of fatigue microdamage in cortical bone specimens is commonly
      measured by a modulus or stiffness degradation after normalizing tissue
      heterogeneity by the initial modulus or stiffness of each specimen measured
      during a preloading step. In the first experiment, the initial specimen modulus
      defined using linear elastic beam theory (LEBT) was shown to be nonlinearly
      dependent on the preload level, which subsequently caused systematic error in the
      amount and rate of damage accumulation measured by the LEBT modulus degradation.
      Therefore, the secant modulus is recommended for measurements of the initial
      specimen modulus during preloading. In the second experiment, different measures
      of mechanical degradation were directly compared and shown to result in widely
      varying estimates of damage accumulation during fatigue. After loading to 400,000
      cycles, the normalized LEBT modulus decreased by 26% and the creep strain ratio
      decreased by 58%, but the normalized secant modulus experienced no degradation
      and histology revealed no significant differences in microcrack density. The LEBT
      modulus was shown to include the combined effect of both elastic (recovered) and
      creep (accumulated) strain. Therefore, at minimum, both the secant modulus and
      creep should be measured throughout a test to most accurately indicate damage
      accumulation and account for different damage mechanisms. Histology revealed
      indentation of tissue adjacent to roller supports, with significant sub-surface
      damage beneath large indentations, accounting for 22% of the creep strain on
      average. The indentation of roller supports resulted in inflated measures of the
      LEBT modulus degradation and creep. The results of this study suggest that
      investigations of fatigue microdamage in cortical bone should avoid the use of
      four-point bending unless no other option is possible.

PMID- 19394020
TI  - Analysis of swimmers' velocity during the underwater gliding motion following
      grab start.
AB  - The purpose of this study was to determine the swimmers' loss of speed during the
      underwater gliding motion of a grab start. This study also set out to determine
      the kinematical variables influencing this loss of speed. Eight French national
      level swimmers participated in this study. The swimmers were filmed using 4 mini
      DV cameras during the entire underwater phase. Using the DLT technique and the
      Dempster's anthropometric data, swimmer's movement have been identified. Two
      principal components analysis (PCA) have been used to study the relations between
      the kinematical variables influencing the loss of speed. The swimmers reached a
      velocity between 2.2 and 1.9 ms(-1) after their centre of mass covered a distance
      ranging between 5.63 and 6.01 m from the start wall. For this range of velocity,
      head position was included between 6.02 and 6.51 m. First PCA show that the
      kinematical parameters at the immersion (first image at which the swimmers' whole
      body was under water) are included in the first two components. Second PCA show
      that the knee, hip and shoulder angles can be included in the same component. The
      present study identified the optimal instant for initiating underwater leg
      movements after a grab start. This study also showed that the performance during
      the underwater gliding motion is determined as much by variables at the immersion
      as by the swimmer's loss of speed. It also seems that to hold the streamlined
      position the synergetic action of the knee, the hip and the shoulder is
      essential.

PMID- 19394021
TI  - Validating a voxel-based finite element model of a human mandible using digital
      speckle pattern interferometry.
AB  - Finite element analysis is a powerful tool for predicting the mechanical
      behaviour of complex biological structures like bones, but to be confident in the
      results of an analysis, the model should be validated against experimental data.
      In such validation experiments, the strains in the loaded bones are usually
      measured with strain gauges glued to the bone surface, but the use of strain
      gauges on bone can be difficult and provides only very limited data regarding
      surface strain distributions. This study applies the full-field strain
      measurement technique of digital speckle pattern interferometry to measure
      strains in a loaded human mandible and compares the results with the predictions
      of voxel-based finite element models of the same specimen. It is found that this
      novel strain measurement technique yields consistent, reliable measurements.
      Further, strains predicted by the finite element analysis correspond well with
      the experimental data. These results not only confirm the usefulness of this
      technique for future validation studies in the field of bone mechanics, but also
      show that the modelling approach used in this study is able to predict the
      experimental results very accurately.

PMID- 19394022
TI  - The effects of preconditioning strain on measured tissue properties.
AB  - Characterizing the mechanical properties of soft biological tissues presents a
      formidable challenge. In order to ensure that the structure of the specimens is
      at a repeatable reference state, preconditioning is commonly performed before the
      actual test. However, the exact mechanisms of preconditioning remain unclear and
      more research on this issue needs to be undertaken so that the methods for
      preconditioning can be refined to reduce experimental variability. Previous
      studies have suggested that the choice of preconditioning strain may influence
      the measured properties. In this study, uniaxial tests were performed on three
      groups of spinal cord tissues. Two groups (Groups 1 and 2) were preconditioned at
      5% strain and tested to 5% and 2% each, while the third (Group 3) was
      preconditioned at 2% strain and tested to 2%. The peak stress measured at 2%
      strain for group 3 was 0.0054+/-0.0035MPa and this was significantly higher than
      group 2 (134%; p=0.015) and group 1 (p=0.005). However, the ratio of peak to
      equilibrium stress and the relaxation time were similar for both preconditioning
      strains. This study suggests that in future work, the preconditioning strain
      should be reported and the highest strain being used in the study should be used
      for preconditioning. This is important to allow meaningful comparison of test
      data within the study and also with other studies.

PMID- 19394023
TI  - Modular control of human walking: a simulation study.
AB  - Recent evidence suggests that performance of complex locomotor tasks such as
      walking may be accomplished using a simple underlying organization of co-active
      muscles, or "modules", which have been assumed to be structured to perform task
      specific biomechanical functions. However, no study has explicitly tested whether
      the modules would actually produce the biomechanical functions associated with
      them or even produce a well-coordinated movement. In this study, we generated
      muscle-actuated forward dynamics simulations of normal walking using muscle
      activation modules (identified using non-negative matrix factorization) as the
      muscle control inputs to identify the contributions of each module to the
      biomechanical sub-tasks of walking (i.e., body support, forward propulsion, and
      leg swing). The simulation analysis showed that a simple neural control strategy
      involving five muscle activation modules was sufficient to perform the basic sub
      tasks of walking. Module 1 (gluteus medius, vasti, and rectus femoris) primarily
      contributed to body support in early stance while Module 2 (soleus and
      gastrocnemius) contributed to both body support and propulsion in late stance.
      Module 3 (rectus femoris and tibialis anterior) acted to decelerate the leg in
      early and late swing while generating energy to the trunk throughout swing.
      Module 4 (hamstrings) acted to absorb leg energy (i.e., decelerate it) in late
      swing while increasing the leg energy in early stance. Post-hoc analysis revealed
      an additional module (Module 5: iliopsoas) acted to accelerate the leg forward in
      pre- and early swing. These results provide evidence that the identified modules
      can act as basic neural control elements that generate task-specific
      biomechanical functions to produce well-coordinated walking.

PMID- 19394024
TI  - Local strain measurement reveals a varied regional dependence of tensile tendon
      mechanics on glycosaminoglycan content.
AB  - Proteoglycans (PG) and their associated glycosaminoglycan (GAG) side chains are
      known to play a key role in the bearing of compressive loads in cartilage and
      other skeletal connective tissues. In tendons and connective tissues that are
      primarily loaded in tension, the influence of proteoglycans on mechanical
      behavior is debated due to conflicting experimental evidence that alternately
      supports or controverts a functional role of proteoglycans in bearing tensile
      load. In this study we sought to better reconcile these conflicting data by
      investigating the possibility that GAG content is differentially related to
      tensile tendon mechanics depending upon the anatomical subregion one considers.
      To test this hypothesis, we quantified the mechanical consequences of
      proteoglycan disruption within specific tendon anatomical subregions using an
      optical-mechanical measurement approach. Achilles tendons from adult mice were
      treated with chondroitinase ABC to obtain two groups consisting of native tendons
      and GAG-depleted tendons. All the tendons were mechanically tested and imaged
      with high-resolution digital video in order to optically quantify tendon strains.
      Tendon surface strains were locally analyzed in three main subregions: the
      central midsubstance, and the proximal and distal midsubstance near the muscle
      and bone insertions, respectively. Upon GAG digestion, the tendon midsubstance
      softened appreciably near the bone insertion, while elastic modulus in the
      central and proximal thirds was unchanged. Thus the contribution of PGs to
      tensile tendon mechanics is not straightforward and points to a heterogeneous and
      complex structure-function relationship in tendon. This study further highlights
      the importance of performing local strain analysis with regard to tensile tendon
      mechanics.

PMID- 19394025
TI  - In-vitro experimental assessment of a new robust algorithm for hip joint centre
      estimation.
AB  - Hip joint centre (HJC) localization is used in several biomedical applications,
      such as movement analysis and computer-assisted orthopaedic surgery. The purpose
      of this study was to validate in vitro a new algorithm (MC-pivoting) for HJC
      computation and to compare its performances with the state-of-the-art (least
      square approach-LSA). The MC-pivoting algorithm iteratively searches for the 3D
      coordinates of the point belonging to the femoral bone that, during the
      circumduction of the femur around the hip joint (pivoting), runs the minimum
      length trajectory. The algorithm was initialized with a point distribution that
      can be considered close to a Monte Carlo simulation sampling all around the LSA
      estimate. The performances of the MC-pivoting algorithm, compared with LSA, were
      evaluated with tests on cadavers. Dynamic reference frames were applied on both
      the femur and the pelvis and were tracked by an optical localizer. Results proved
      the algorithm accuracy (1.7mm+/-1.6, 2.3-median value+/-quartiles), reliability
      (smaller upper quartiles of the errors distribution with respect to LSA) and
      robustness (reduction of the errors also in case of large pelvis displacements).

PMID- 19394026
TI  - Carbon nanotube-coated solid-phase microextraction metal fiber based on sol-gel
      technique.
AB  - A novel carbon nanotube (CNT)-coated solid-phase microextraction fiber was
      prepared based on sol-gel technique. Commonly used fragile fused silica fiber was
      replaced with stainless steel wire, which made the fiber unbreakable. An approach
      was also proposed for batch producing, and good reproducibilities for fiber to
      fiber and between fibers were achieved. Experiments showed that the sol-gel-CNT
      fiber exhibited high thermal stability to resist 350 degrees C and excellent
      solvent durability in methanol and acetonitrile. Compared to commercial
      polydimethylsiloxane (PDMS) fiber, the sol-gel-CNT fiber represented
      significantly improved extraction efficiencies for both polar (phenols) and non
      polar (benzene, toluene, ethylbenzene, and o-xylene) compounds. Meanwhile, no
      replacement effect, low carry-over and wide linear range demonstrated that the
      newly prepared sol-gel-CNT coating has liquid properties, which allow a
      relatively easy quantification procedure. Moreover, the characterization of the
      sol-gel-CNT coating was also evaluated with McReynold probe solutes. The results
      showed that the coating has better affinity for all the five types of solutes
      compared to commercial 7microm PDMS fiber, which suggested that the coating has
      the potential to be developed as GC stationary phase.

PMID- 19394027
TI  - Determination of thromboxanes, leukotrienes and lipoxins using high-temperature
      capillary liquid chromatography-tandem mass spectrometry and on-line sample
      preparation.
AB  - An on-line strong cation-exchange (SCX)-reversed-phase (RP) capillary liquid
      chromatographic (cLC) method with ion-trap tandem mass spectrometric (IT-MS/MS)
      detection for the simultaneous determination of thromboxane (TX) B(2), TXB(3),
      leukotriene (LT) B(4), LTD(4) and lipoxin (LX) A(4) in cell culture supernatants
      was developed and validated. In the present method, a high temperature (70
      degrees C) was used for the separation on the analytical column to obtain
      efficient chromatography of the thromboxanes. An on-line sample preparation was
      performed, where peptides/proteins contained in the matrix were removed by the
      SCX column. Sample pre-treatment included dilution and filtration, and the
      analysis time including all sample preparation steps was 60min per sample. Limits
      of detection in the range of 1-4ng/mL cell culture supernatant, recoveries
      between 30% and 100%, within day precisions of less than 20% RSD and between day
      precisions of less than 30% RSD were obtained. Human mesenchymal stem cells
      (hMSCs) were stimulated with cytokine-containing supernatants derived from
      activated human T lymphocytes, and thromboxane, leukotriene and lipoxin
      production was analysed using the developed method. TXB(2) was found in cultures
      from both non-differentiated and differentiated hMSCs that were stimulated with a
      cytokine-containing supernatant obtained from activated T-cells.

PMID- 19394028
TI  - Intercalation of both CTMAB and Al13 into montmorillonite.
AB  - Clays intercalated with both organic cations and hydroxy-metal cations, also
      known as inorganic-organic clays (IOCs), have drawn great interests in the recent
      years because they possess the properties of both organoclays and pillared
      layered clays (PILCs). In this work, cetyltrimethyl ammonium bromide (CTMAB) and
      hydroxy-aluminum ([Al13O4(OH)24(H2O)12]7+ or Al13) were selected as the
      representatives of organic cations and hydroxy-metal cations, and three different
      methods were employed for the intercalation of montmorillonite at various
      CTMAB/Al13 ratios. This work aims to provide some novel information for
      clarifying the structural characteristics of IOCs. The experimental results
      showed that the structures of the resulting IOCs strongly depended on the
      intercalation methods and CTMAB/Al13 ratio. Both the intercalation agents could
      be intercalated into montmorillonite if they were used simultaneously for the
      intercalation, or if Al13 was intercalated after CTMAB, and the resulting IOCs
      were shown to have large basal spacing and small surface areas. However, if Al13
      was intercalated first, the loading amounts of CTMAB would decrease significantly
      when the used Al13 amounts were relatively large (> or = 4 mmol Al/g
      montmorillonite). This could be attributed to the "lock" effect of
      montmorillonite's layers by the pre-intercalated Al13, and the basal spacing
      values of the resulting IOCs were shown to be equal to those of the PILCs.

PMID- 19394029
TI  - Preschoolers' use of feedback for flexible behavior: insights from a
      computational model.
AB  - This study addressed preschoolers' cognitive flexibility in an inductive task
      requiring response feedback processing to infer relevant task goals. A total of
      63 4- to 6-year-olds were tested on a perceptual matching task in which they
      needed to switch attention among three colors. A computational model was designed
      to track down how responses to positive and negative feedback changed as children
      progressed through the task. The results showed that children's differential
      response to positive and negative feedback developed with age. In addition, age
      differences in feedback responding increased as the task unfolded. These findings
      are interpreted as reflecting an increase in flexibility with age in terms of
      growing efficiency in feedback processing.

PMID- 19394030
TI  - Improving decision analyses: parent preferences (utility values) for pediatric
      health outcomes.
AB  - OBJECTIVE: To gather and calculate utilities for a wide range of health states in
      the pediatric population. STUDY DESIGN: The study subjects, parents or guardians
      at least 18 years of age with at least 1 child under age 18 years, were recruited
      through our Pediatric Research Network (PResNet). Recruitment locations included
      pediatric clinics, the Indiana State Fair, and public and private conventions.
      Each subject's utilities were assessed on 3 random health states out of 29 chosen
      for the study. Both the time trade-off and standard gamble methods were used to
      measure utilities. RESULTS: Utilities were assessed in a total of 4016
      participants (a recruitment rate of 88%). Utility values ranged from a high for
      acute otitis media (0.96 by standard gamble; 0.97 by time trade-off) to a low for
      severe mental retardation (0.59 by standard gamble; 0.51 by time trade-off).
      CONCLUSIONS: Our extensive data set of utility assessments for a wide range of
      disease states can aid future economic evaluations of pediatric health care.

PMID- 19394031
TI  - Prenatal detection of congenital heart disease.
AB  - OBJECTIVES: To define current frequency of prenatal detection of congenital heart
      disease (CHD), factors affecting prenatal detection, and its influence on
      postnatal course. STUDY DESIGN: We prospectively identified all fetuses and
      infants < or =6 months of age with major CHD at 3 referral centers in Northern
      California over 1 year; we obtained prenatal and demographic data, reviewed
      prenatal ultrasound (US) and postnatal records, and used logistic regression to
      analyze maternal, fetal, and prenatal-care provider risk factors for prenatal
      diagnosis. RESULTS: Ninety-eight of 309 infants with major CHD had prenatal
      diagnosis (36% accounting for 27 pregnancy terminations); 185 infant-families
      participated in the postnatal survey, and although 99% had prenatal US, only 28%
      were prenatally diagnosed. Anomalous pulmonary venous return (0%), transposition
      of the great arteries (19%), and left obstructive lesions (23%) had the lowest
      prenatal detection. Heterotaxy (82%), single ventricle (64%), and HLHS (61%) had
      the highest. Prenatal diagnosis was higher at university versus community
      practices (P = .001). Sociodemographics were not associated with prenatal
      diagnosis. Infants diagnosed prenatally were less frequently ventilated (P < .01)
      or treated with prostaglandin (P < .05). CONCLUSIONS: Prenatal detection of major
      CHD significantly alters postnatal course but remains low despite nearly
      universal US. CHD type and US practice type are important determinants of
      prenatal detection.

PMID- 19394033
TI  - Use of racecadotril as outpatient treatment for acute gastroenteritis: a
      prospective, randomized, parallel study.
AB  - OBJECTIVE: To compare the efficacy of therapy with racecadotril plus oral
      rehydration versus oral rehydration alone in children with gastroenteritis in an
      outpatient setting care. STUDY DESIGN: Prospective, randomized, open and parallel
      study performed in a Pediatric Emergency Service of a tertiary care hospital. The
      study included 189 patients, ages 3 to 36 months, with acute gastroenteritis: 94
      were administered an oral rehydration solution (OR), 94 received oral rehydration
      solution plus racecadotril (OR + R). The principal variable studied was the
      number of bowel movements in 48 hours after initiating treatment. RESULTS: The
      groups were comparable clinically and epidemiologically at enrollment. No
      significant differences were found in the number of bowel movements between the 2
      groups 48 hours after initiating treatment (4.1 +/- 2.7 bowel movements in the OR
      group vs 3.8 +/- 2.4 bowel movements in the OR + R group). No differences were
      found in the average duration of gastroenteritis (4.7 +/- 2.2 days in the OR
      group, 4.0 +/- 2.1 days in the OR + R group; P = .15). The incidence of adverse
      events was similar in both groups (19 patients [20.2%] in the OR group, 18
      patients [19.1%] in the OR + R group). CONCLUSIONS: In our study group, the use
      of racecadotril did not improve the symptoms of diarrhea compared with standard
      rehydration therapy.

PMID- 19394032
TI  - Epidemiology and risk factors for thromboembolic complications of childhood
      nephrotic syndrome: a Midwest Pediatric Nephrology Consortium (MWPNC) study.
AB  - OBJECTIVES: To identify clinical variables predictive of the risk of
      thromboembolism (TE), and to confirm the incidence of TE in primary and secondary
      childhood nephrotic syndrome (NS). STUDY DESIGN: A comprehensive chart review
      identified 326 children with NS from any cause evaluated between 1999 and 2006.
      These patients had a total of 1472.8 patient-years of follow-up. Comparison
      statistics, survival analysis, and logistic regression were used to define TE
      epidemiology and clinical risk factors. RESULTS: We found that 9.2% of our cohort
      had experienced at least 1 TE. The overall incidence was 20.4 patients with
      TEs/1000 patient-years. The median time to the first TE was 70.5 days after
      diagnosis of NS. Deep venous thrombosis was the most common TE (76%) and was
      frequently associated with the use of a central venous catheter (45%).
      Significant independent predictors of TE included age > or = 12 years at onset of
      NS (P < .0001), severity of proteinuria (P < .0001), and history of TE preceding
      diagnosis of NS (P < .0001). Life- or limb-threatening TEs represented 23.7% of
      the events. CONCLUSIONS: Children with NS should be carefully followed for TE,
      particularly those who are age 12 years or older, have severe proteinuria, or
      have a previous history of TE.

PMID- 19394034
TI  - The health and cost impact of care delay and the experimental impact of insurance
      on reducing delays.
AB  - OBJECTIVE: To examine whether delays in seeking care are associated with worse
      health outcomes or increased treatment costs in children, and then assess whether
      insurance coverage reduces these delays. STUDY DESIGN: We use data on 4070
      children younger than 5 years from the Quality Improvement Demonstration Study, a
      randomized controlled experiment assessing the effects of increasing insurance
      coverage. We examined whether delay in care, defined as greater than 2 days
      between the onset of symptoms and admission to the study district hospitals, is
      associated with wasting or having positive C-reactive protein levels on
      discharge, and with total charge for hospital admission; we also evaluated
      whether increased benefit coverage and enrollment reduced the likelihood of
      delay. RESULTS: Delay is associated with 4.2% and 11.2% percentage point
      increases in the likelihood of wasting (P = .08) and having positive C-reactive
      protein levels (P = .03), respectively, at discharge. On average, hospitalization
      costs were 1.9% higher with delay (P = .04). Insurance intervention results in 5
      additional children in 100 not delaying going to the hospital (P = .02).
      CONCLUSIONS: In this population, delayed care is associated with worse health
      outcomes and higher costs. Access to insurance reduced delays; thus insurance
      interventions may have positive effects on health outcomes.

PMID- 19394035
TI  - Delayed diagnosis in duchenne muscular dystrophy: data from the Muscular
      Dystrophy Surveillance, Tracking, and Research Network (MD STARnet).
AB  - OBJECTIVE: To identify key factors for the delay in diagnosis of Duchenne
      muscular dystrophy (DMD) without known family history. STUDY DESIGN: The cohort
      comes from the Muscular Dystrophy Surveillance, Tracking, and Research Network
      (MD STARnet), a multistate, multiple-source, population-based surveillance system
      that identifies and gathers information on all cases of Duchenne and Becker
      muscular dystrophy born since 1982. We analyzed medical records of 453 Duchenne
      and Becker muscular dystrophy boys to document the time course and steps taken to
      reach a definitive diagnosis. RESULTS: Among 156 boys without known family
      history of DMD prior to birth, first signs or symptoms were noted at a mean age
      of 2.5 years. Concerns resulted in primary care provider evaluation of the child
      at a mean age of 3.6 years. Mean age at time of initial creatine kinase was 4.7
      years. Mean age at definitive diagnosis of DMD was 4.9 years. CONCLUSIONS: There
      is a delay of about 2.5 years between onset of DMD symptoms and the time of
      definitive diagnosis, unchanged over the previous 2 decades. This delay results
      in lost opportunities for timely genetic counseling and initiation of
      corticosteroid treatment. We recommend checking creatine kinase early in the
      evaluation of boys with unexplained developmental delay.

PMID- 19394036
TI  - Clustering of dietary intake and sedentary behavior in 2-year-old children.
AB  - OBJECTIVE: To examine clustering of energy balance-related behaviors (EBRBs) in
      young children. This is crucial because lifestyle habits are formed at an early
      age and track in later life. This study is the first to examine EBRB clustering
      in children as young as 2 years. STUDY DESIGN: Cross-sectional data originated
      from the Child, Parent and Health: Lifestyle and Genetic Constitution (KOALA)
      Birth Cohort Study. Parents of 2578 2-year-old children completed a
      questionnaire. Correlation analyses, principal component analyses, and linear
      regression analyses were performed to examine clustering of EBRBs. RESULTS: We
      found modest but consistent correlations in EBRBs. Two clusters emerged: a
      "sedentary-snacking cluster" and a "fiber cluster." Television viewing clustered
      with computer use and unhealthy dietary behaviors. Children who frequently
      consumed vegetables also consumed fruit and brown bread more often and white
      bread less often. Lower maternal education and maternal obesity were associated
      with high scores on the sedentary-snacking cluster, whereas higher educational
      level was associated with high fiber cluster scores. CONCLUSIONS: Obesity-prone
      behavioral clusters are already visible in 2-year-old children and are related to
      maternal characteristics. The findings suggest that obesity prevention should
      apply an integrated approach to physical activity and dietary intake in early
      childhood.

PMID- 19394037
TI  - Cardiovascular effects of longer-term, high-dose OROS methylphenidate in
      adolescents with attention deficit hyperactivity disorder.
AB  - OBJECTIVE: To examine the effects of high doses of extended-release
      methylphenidate (OROS MPH) on cardiovascular variables in adolescents with
      attention deficit hyperactivity disorder (ADHD). STUDY DESIGN: ECG indices plus
      systolic blood pressure (SBP), diastolic BP (DBP) and heart rate (HR) were
      assessed during an open-label study of OROS MPH in 114 adolescents with ADHD
      (doses up to 1.5 mg/kg/d). Cardiovascular parameters were assessed at 6 weeks and
      6 months. RESULTS: Small but statistically significant changes in DBP and HR were
      observed at 6 weeks, without further increases up to 6 months' follow-up. A small
      but statistically significant increase in SBP was observed over time. Twenty-nine
      percent of patients had isolated elevations in BP readings prior to study entry,
      and 14% had >3 consecutive visits at which elevated BP were observed during OROS
      MPH treatment. No clinically significant changes in ECG parameters were observed.
      No serious cardiovascular adverse events occurred. CONCLUSIONS: Treatment with
      relatively high doses of OROS MPH was associated with small but statistically
      significant mean increases in BP and HR, primarily during the first 6 weeks of
      treatment, without clinically meaningful changes in ECG. These observations are
      consistent with previous reports using lower doses.

PMID- 19394038
TI  - Maternal corticosteroid use and hypospadias.
AB  - OBJECTIVE: To explore whether women who reported corticosteroid use during
      pregnancy were more likely to deliver an infant with hypospadias than women who
      did not. STUDY DESIGN: The analysis encompassed data on deliveries with an
      estimated due date between 1997 and 2004 from the National Birth Defects
      Prevention Study, a large population-based, case-control study conducted in the
      United States. Included were 1165 cases of moderate to severe hypospadias and
      3000 nonmalformed male controls. RESULTS: The mothers of 39 cases (3.3%) and 62
      controls (2.1%) reported using a corticosteroid medication during the period
      extending from 4 weeks before conception to 14 weeks after conception. The odds
      ratio (OR) for any corticosteroid exposure versus no corticosteroid exposure was
      1.6 (95% confidence interval [CI] = 1.1 to 2.5); after adjustment for maternal
      race/ethnicity, education, age, and study site, it was 1.3 (95% CI = 0.8 to 2.0).
      Analyses by route of administration and specific component suggest that elevated
      ORs occurred only for nasal spray/inhaled corticosteroids (OR = 1.5; 95% CI = 0.9
      to 2.6). CONCLUSIONS: Maternal use of corticosteroid medications was weakly
      associated with risk of hypospadias, but the association was negligible after
      adjustment for potential confounders.

PMID- 19394039
TI  - Childhood onset major depressive disorder: course of illness and psychiatric
      comorbidity in a community sample.
AB  - OBJECTIVE: To examine the effect of childhood-onset major depressive disorder
      (MDD) on course of illness and psychiatric comorbidity, as compared with
      adolescent- and adult-onset MDD, in a large nonclinical sample. STUDY DESIGN:
      This study included 6778 civilian noninstitutionalized participants in the
      National Epidemiologic Survey on Alcohol and Related Conditions with
      nonpsychotic, non-substance-induced MDD. Subjects were divided into 3 groups on
      the basis of age at first episode of MDD: childhood-onset (CHLD; onset < or =12
      yrs, n = 372), adolescent-onset (ADOL; onset 13 to 17 years, n = 854), and adult
      onset (ADLT; onset > or =18 years, n = 5552). RESULTS: Compared with subjects
      with ADLT, CHLD MDD was associated with a greater number of MDD episodes, longer
      episode duration, increased suicidality, and increased need for hospitalization
      for MDD compared with adult-onset illness. Subjects with CHLD had a higher rate
      of psychiatric comorbidity and were more likely to have a parental history of
      MDD. Among subjects treated for MDD, latency from MDD onset to treatment was
      greater among subjects with CHLD compared with subjects with ADLT. Data for
      subjects with ADOL was intermediate to those of subjects with CHLD and ADLT.
      CONCLUSIONS: This epidemiologic study confirms and extends clinical findings of
      childhood-onset MDD as a more familial form of illness associated with increased
      comorbidity, suicidality, and treatment use.

PMID- 19394040
TI  - Incidence of bleeding complications in pediatric patients with type 1 von
      Willebrand disease undergoing adenotonsillar procedures.
AB  - OBJECTIVE: To review the incidence of postoperative bleeding in children with
      type 1 von Willebrand disease (VWD) who were treated with a single institution
      protocol. STUDY DESIGN: We performed a retrospective study to determine the
      postoperative hemorrhage rate in pediatric patients with type 1 VWD who were
      treated via the Children's Hospital of Philadelphia institutional protocol. This
      protocol utilizes intravenous desmopressin (DDAVP), oral aminocaproic acid, and
      overnight observation. RESULTS: Between the years of 2000 to 2006, 41 children
      with type 1 VWD underwent an adenotonsillar procedure and were treated with this
      protocol. Seven patients (17%) experienced delayed (>24 hours after surgery)
      postoperative hemorrhage requiring intervention. Five of the 7 patients required
      cautery to control the bleeding, and the remaining 2 patients responded to DDAVP
      and aminocaproic acid alone. Older age and lower VW antigen levels were
      associated with postoperative hemorrhage (P = .05). CONCLUSIONS: Despite
      therapeutic intervention to decrease the risk of postoperative hemorrhage, the
      incidence of hemorrhage was higher in pretreated patients with type 1 VWD than in
      children without bleeding disorders. Further prospective studies are necessary to
      determine the optimal treatment to reduce bleeding complications in these
      patients.

PMID- 19394041
TI  - Neurobehavior at term and white and gray matter abnormalities in very preterm
      infants.
AB  - OBJECTIVE: To examine the relationship between very preterm infant neurobehavior
      at term and concurrent magnetic resonance-defined cerebral abnormalities. STUDY
      DESIGN: 168 very preterm infants (birth weight <1250 g or gestation <30 weeks)
      were examined at term with 2 standardized neurobehavioral assessments, the
      Revised Hammersmith Neonatal Neurological Examination and the Neonatal Intensive
      Care Unit Network Neurobehavioral Scale. The relationship between composite
      neurobehavioral scores and qualitative white and gray matter abnormalities on
      magnetic resonance imaging was determined. RESULTS: Poorer neurobehavioral
      performance related to magnetic resonance-defined cerebral abnormalities.
      Composite neurobehavioral scores related to the total grade of white matter
      abnormality, and worse neurobehavior related most strongly to 2 components of
      this grade: white matter signal abnormalities and reduction in white matter
      volumes. Neurobehavior was not related to the total grade of gray matter
      abnormality. However, delayed gyral maturation, a component of the total gray
      matter grade, was related to poorer performance on both neurobehavioral scales.
      CONCLUSION: Very preterm infant neurobehavior at term is related to concurrent
      cerebral abnormalities in both white and gray matter defined by qualitative
      magnetic resonance imaging.

PMID- 19394042
TI  - Long-term neurodevelopment of children exposed to maternal nausea and vomiting of
      pregnancy and diclectin.
AB  - OBJECTIVE: To determine the effects of nausea and vomiting of pregnancy (NVP) and
      its treatment with diclectin on child neurodevelopment. STUDY DESIGN: An
      observational cohort study of mother-child pairs ascertained via a pregnancy call
      in center was conducted. Three groups of children were studied: 45 with NVP and
      diclectin, 47 with NVP no diclectin, and 29 with no NVP. Phone calls to mothers
      during pregnancy and 6 to 9 months after childbirth yielded information on
      pregnancy, birth, and early child development. Children aged 3 to 7 years
      received a comprehensive set of psychological tests. Mothers were assessed for IQ
      and socioeconomic status. RESULTS: All children scored in the normal range for
      IQ, with the NVP-exposed group scoring higher than the non-exposed group on
      Performance IQ (P < .02), NEPSY Verbal Fluency (P < .003) and Phonological
      Processing (P < .004), and McCarthy Numerical Memory (P < .004). Predictors of
      enhanced results were NVP severity and maternal IQ. CONCLUSIONS: NVP has an
      enhancing effect on later child outcome. Diclectin does not appear to adversely
      affect fetal brain development and can be used to control NVP when clinically
      indicated.

PMID- 19394044
TI  - Parental depressive symptoms: relationship to child development, parenting,
      health, and results on parent-reported screening tools.
AB  - OBJECTIVE: To determine whether parents with depressive symptoms can accurately
      complete parent-reported developmental screens, and to explore effects of
      parental depressive symptoms on perceptions of children's health and parenting
      behaviors. STUDY DESIGN: A total of 382 parent-child (ages 0 to 2 years) dyads
      from pediatric sites across 17 U.S. states were evaluated with the directly
      administered and parent-reported Brigance Infant Toddler Screen, the Brigance
      Parent-Child Interactions Scale, a child development and health rating scale, and
      a caretaker depression screen. Groups were compared by parental status by
      depression screening. RESULTS: Fifteen percent of parents had positive scores on
      screening for depression. Parents with a positive screen result for depression
      were twice as likely to rate their children as below average or average and to
      perceive health problems in their children. Their children were 1.7 times more
      likely to perform below Brigance Screen cutoffs. Parents with a positive screen
      result for depression were as accurate as parents with a negative screen result
      for depression in identifying delayed or average development but were
      significantly less likely to rate their above-average children as such and
      reported fewer positive parenting practices. CONCLUSION: Parents with a positive
      depression screen result were as accurate in identifying developmental problems
      as parents with a negative depression screen result. Parental depressive symptoms
      are negatively associated with parenting behaviors, parental perspective on
      health and development, and child outcomes, which supports screening for
      depression and intervening promptly.

PMID- 19394043
TI  - Predictors of insulin regimens and impact on outcomes in youth with type 1
      diabetes: the SEARCH for Diabetes in Youth study.
AB  - OBJECTIVES: To describe the insulin regimens used to treat type 1 diabetes
      mellitus (T1DM) in youth in the United States, to explore factors related to
      insulin regimen, and to describe the associations between insulin regimen and
      clinical outcomes, particularly glycemic control. STUDY DESIGN: A total of 2743
      subjects participated in the SEARCH for Diabetes in Youth study, an observational
      population-based study of youth diagnosed with T1DM, conducted at 6 centers. Data
      collected during a study visit included clinical and sociodemographic
      information, body mass index, laboratory measures, and insulin regimen. RESULTS:
      Sociodemographic characteristics were associated with insulin regimen. Insulin
      pump therapy was more frequently used by older youth, females, non-Hispanic
      whites, and families with higher income and education (P = .02 for females, P <
      .001 for others). Insulin pump use was associated with the lowest hemoglobin A1C
      levels in all age groups. A1C levels were >7.5% in >70% of adolescents,
      regardless of regimen. CONCLUSIONS: Youth using insulin pumps had the lowest A1C;
      A1C was unacceptably high in adolescents. There is a need to more fully assess
      and understand factors associated with insulin regimens recommended by providers
      and the influence of race/ethnicity, education, and socioeconomic status on these
      treatment recommendations and to develop more effective treatment strategies,
      particularly for adolescents.

PMID- 19394045
TI  - Sporadic in utero generalized edema caused by mutations in the lymphangiogenic
      genes VEGFR3 and FOXC2.
AB  - OBJECTIVES: To investigate the genetic causes of idiopathic sporadic prenatal
      generalized edema. STUDY DESIGN: In a series of 12 patients, in whom in utero
      generalized skin edema or hydrops fetalis had been diagnosed, we screened 3
      lymphangiogenic genes, VEGFR3, FOXC2, and SOX18. RESULTS: In 3 of the patients,
      we identified a mutation: 2 in VEGFR3 and 1 in FOXC2. Two of the mutations were
      de novo and one was either de novo or nonpenetrant inherited. In these patients,
      the generalized edema resorbed spontaneously, either in utero or after birth. In
      the 2 individuals with a VEGFR3 mutation, edema remained limited to lower limbs.
      CONCLUSIONS: Mutations in the VEGFR3 and FOXC2 genes account for a subset of
      patients with unexplained in utero generalized subcutaneous edema and hydrops
      fetalis without family history of lymphedema. Lymphangiogenic genes should be
      screened for mutations in sporadic patients diagnosed with fetal edema.

PMID- 19394046
TI  - Hyperglycemia during induction therapy is associated with poorer survival in
      children with acute lymphocytic leukemia.
AB  - OBJECTIVES: To investigate whether children with acute lymphocytic leukemia (ALL)
      who have development of hyperglycemia during induction may have worse relapse
      free (RFS) and overall survival (OS) rates. STUDY DESIGN: A review of 167
      children diagnosed with ALL between 1999 to 2002 at Texas Children's Hospital was
      performed. Blood glucose concentrations during induction therapy were reviewed;
      patients were assigned to 3 groups: euglycemia (blood glucose < 140 mg/dL), mild
      hyperglycemia (blood glucose between 140-200 mg/dL), and overt hyperglycemia
      (blood glucose > 200 mg/dL). RFS and OS among groups were compared by use of
      Kaplan-Meier and Cox-proportional hazard analyses, adjusting for potential
      confounding variables. RESULTS: The median follow-up in survivors was 6 years;
      there were 18 deaths and 36 relapses. Overt hyperglycemia was seen in 56 (34%)
      patients. Patients with overt hyperglycemia had poorer RFS (68% +/- [SE] 6.7 vs
      85% +/- 3.6, P = .025) and OS (74% +/- 6.1 vs 96% +/- 1.9, P < .0001) at 5 years
      than their counterparts. Patients with overt hyperglycemia had 6.2 times (95% CI
      1.6-24.7, P = .01) greater risk for death, independent of risk group and type of
      steroid. CONCLUSIONS: Overt hyperglycemia may be an independent predictor of
      survival in children with ALL.

PMID- 19394047
TI  - National rates of diarrhea-associated ambulatory visits in children.
AB  - OBJECTIVE: To estimate national rates of ambulatory healthcare visits due to
      diarrhea- and rotavirus-associated illness before the introduction of rotavirus
      vaccine. STUDY DESIGN: Annual rates for diarrhea-associated visits in children
      age < 5 years were calculated for 1995-2004 using National Ambulatory Medical
      Care Survey, National Hospital Ambulatory Medical Care Survey, and US Census
      Bureau data. Rates by age, race, and time period were compared using Poisson
      regression. RESULTS: Annual rates of outpatient and emergency department (ED)
      visits for 1995-2004 were 955 (95% confidence interval [CI] = 803 to 1107) and
      314 (95% CI = 278 to 350)/10,000 person-years, respectively. Annual outpatient (P
      = .470) and ED (P = .734) visit rates remained stable from 1995 to 2004.
      Outpatient visits were less frequent in African Americans than Caucasians
      (716/10,000 person-years vs 1012/10,000 person-years; P < .05; incidence rate
      ratio [IRR] = 0.71; 95% CI = 0.51 to 0.99), whereas ED visits were more frequent
      in African Americans than Caucasians (520/10,000 person-years vs 286/10,000
      person-years; P < .05; IRR = 1.83; 95% CI = 1.58 to 2.11). Approximately 29% of
      outpatient diarrhea-associated outpatient visits (273/10,000 person-years; 95% CI
      = 145 to 401) and 25% of diarrhea-associated ED visits (78/10,000 person-years;
      95% CI = 64 to 83) were due to rotavirus. CONCLUSIONS: Diarrhea- and rotavirus
      associated illness is associated with significant healthcare utilization. Future
      studies are needed to investigate factors causing differences in healthcare use
      by race and to explore the impact of the rotavirus vaccine.

PMID- 19394048
TI  - Pharmacodynamics and systemic exposure of esomeprazole in preterm infants and
      term neonates with gastroesophageal reflux disease.
AB  - OBJECTIVE: To characterize the pharmacodynamics and systemic exposure of
      esomeprazole in 26 preterm infants and term neonates with symptoms of
      gastroesophageal reflux and pathologic acid exposure. STUDY DESIGN: Enrolled
      patients received oral esomeprazole 0.5 mg/kg once daily for 7 days. Twenty-four
      hour esophagogastric pH-impedance monitoring was performed at baseline and on day
      7. Pharmacokinetic analysis was performed on day 7. Symptoms occurring during the
      baseline and day 7 studies were recorded on a symptom chart. RESULTS: There were
      no significant differences from baseline to day 7 of therapy in the frequency of
      bolus reflux, consistency of bolus reflux (liquid, mixed, or gas), extent of
      bolus reflux, or bolus clearance time. Acid bolus reflux episodes were reduced on
      therapy (median 30 vs 8, P < .001), as was the reflux index (mean % time
      esophageal pH < 4, 15.7% vs 7.1%, P < .001). The estimated geometric mean of area
      under the plasma concentration time curve during the dosing interval and observed
      maximum plasma concentration was 2.5 micromol x h/L and 0.74 micromol/L,
      respectively. The number of gastroesophageal reflux symptoms recorded over 24
      hours was lower on therapy (median 22 vs 12, P < .05). CONCLUSIONS: In preterm
      infants and term neonates esomeprazole produces no change in bolus reflux
      characteristics despite significant acid suppression.

PMID- 19394049
TI  - The use of exhaled nitric oxide in the diagnosis of asthma in school children.
AB  - OBJECTIVES: To evaluate the yield of the fractional exhaled nitric oxide (FeNO)
      in the diagnosis of asthma compared with spirometry and induced sputum cytologic
      study in school-age children. STUDY DESIGN: Consecutive children referred for
      evaluation of possible asthma were included. At referral, all children completed
      FeNO measurement, sputum induction for eosinophil count (eos%) and spirometry.
      The diagnosis of asthma was performed after 18 months with conventional criteria.
      Receiver operating curves were used to determine cutoff points for disease
      status, and accuracy was calculated. RESULTS: A total of 150 children were
      included: 69 with steroid-naive asthma, 44 without asthma, and 37 with asthma
      treated with controllers. FeNO and eos% levels were significantly higher in those
      with steroid-naive asthma (P < .0001). The area under the receiver operating
      curve for FeNO and eos% were very high compared with forced expiratory volume in
      1 second (0.906, 0.921, 0.606, respectively). The sensitivity, specificity, and
      positive and negative predictive values for best cutoff points of FeNO (19 parts
      per billion) were 80%, 92%, 89%, and 86%, respectively, and were similar to eos%
      (best cutoff = 2.7%): 81%, 92%, 89%, 85%, respectively. CONCLUSIONS: FeNO
      measurement is useful in early diagnosis of pediatric asthma. We suggest
      considering FeNO measurement in the evaluation of children suspected of having
      asthma, especially in cases where the diagnosis is not clear.

PMID- 19394050
TI  - Vascular dementia 2007.

PMID- 19394051
TI  - Ewing's sarcoma family tumors mimicking primary central nervous system neoplasms.
AB  - Ewing's sarcoma family tumors (ESFTs) and embyronal tumors of the central nervous
      system are malignant primitive neuroectodermal tumors (PNETs) that can arise in
      the central nervous system, bones, or soft tissues. When ESFTs involve the
      central nervous system or nearby structures the diagnosis depends on cytogenetics
      and immunohistochemistry as these tumors can appear otherwise histologically
      identical to central PNETs. Correct diagnosis is essential as the treatment
      paradigms for both entities differ. We present two cases of isolated central
      nervous system presentations of ESFTs mimicking primary central nervous system
      neoplasms.

PMID- 19394053
TI  - [Multiple biliary hamartomatosis].

PMID- 19394052
TI  - MuSK-antibody-positive myasthenia gravis in a South Asian population.
AB  - BACKGROUND: MuSK-antibody-positive myasthenia gravis (MuSK-MG) is diagnosed in 0
      40% of cases with generalized seronegative MG in different populations. The
      presence of anti-MuSK antibodies defines a distinct clinico-immuno-pathological
      subtype of MG. We analysed for the first time the serology and clinical
      characteristics of MuSK-MG in a South Asian population. METHODS: 113 patients
      with MG attending Neurology Units in three state hospitals in the district of
      Colombo, Sri Lanka were studied. AChR antibodies were tested in all patients
      whilst MuSK antibodies were tested in patients seronegative for AChR antibodies.
      Sera from patients with other neurological diseases (OND) concurrently attending
      the same hospitals were obtained as controls. RESULTS: Four of 19 AChRAb-negative
      generalised MG patients (21%) were positive for MuSKAbs. Two were women and in 3,
      disease onset was before the age of 30 years. Although 3 of 4 had ocular-bulbar
      involvement at presentation, none had facial or bulbar muscle wasting. Two of the
      4 patients (50%) had developed myasthenic crisis and had required ventilation. A
      good treatment outcome appears to be related to early commencement of
      immunosuppressive medication. None of the patients with ocular MG or OND were
      positive for either AChR or MuSK antibodies. CONCLUSIONS: MuSK-MG is seen in
      about a fifth of generalised seronegative MG patients in Sri Lanka. The clinical
      characteristics are consistent with features described in Caucasian MuSK-MG
      patients.

PMID- 19394054
TI  - Association of soluble intercellular adhesion molecule-1 with insulin resistance
      and metabolic syndrome in Taiwanese.
AB  - Circulating concentrations of soluble cell adhesive molecules are useful
      predictors for the risk of development and progression of atherosclerosis. This
      study was initiated to investigate the association between soluble intercellular
      adhesive molecule-1 (sICAM-1) levels and traditional and emerging cardiovascular
      risk factors, as well as insulin resistance and metabolic syndrome, in a
      Taiwanese population. Six hundred nine unrelated individuals recruited during
      routine health examinations were enrolled for the analysis. In age- and sex
      adjusted regression models, sICAM-1 levels were negatively associated with high
      density lipoprotein cholesterol levels and positively associated with systolic,
      mean, and diastolic blood pressure; body mass index; waist circumference; waist
      hip ratio; the homeostasis model assessment index; fasting serum insulin;
      triglyceride; and C-reactive protein levels. The sICAM-1 levels were also higher
      in subjects with current smoking (P = .001), diabetes mellitus (P = .004),
      insulin resistance (P < .001), and metabolic syndrome (P < .001). The sICAM-1
      levels increased in a stepwise fashion with increasing Framingham risk score
      quartiles (P = .001) and with increasing number of metabolic syndrome components
      (P < .001). In subjects with metabolic syndrome, increased C-reactive protein
      levels were associated with increased sICAM-1 levels (P = .003). In stepwise
      linear regression models, sICAM-1 levels remained associated with current
      smoking, insulin resistance, and metabolic syndrome. In conclusion, our data
      revealed that insulin resistance and metabolic syndrome were associated with
      sICAM-1 levels in Taiwanese. These data provide further evidence of the
      mechanisms of sICAM-1 as a molecular marker for atherosclerosis.

PMID- 19394055
TI  - Fish oil and argan oil intake differently modulate insulin resistance and glucose
      intolerance in a rat model of dietary-induced obesity.
AB  - We investigated the potential metabolic benefits of fish oil (FO) or vegetable
      argan oil (AO) intake in a dietary model of obesity-linked insulin resistance.
      Rats were fed a standard chow diet (controls), a high-fat/high-sucrose (HFHS)
      diet, or an HFHS diet in which 6% of the fat was replaced by either FO or AO
      feeding, respectively. The HFHS diet increased adipose tissue weight and insulin
      resistance as revealed by increased fasting glucose and exaggerated glycemic and
      insulin responses to a glucose tolerance test (intraperitoneal glucose tolerance
      test). Fish oil feeding prevented fat accretion, reduced fasting glycemia, and
      normalized glycemic or insulin responses to intraperitoneal glucose tolerance
      test as compared with HFHS diet. Unlike FO consumption, AO intake failed to
      prevent obesity, yet restored fasting glycemia back to chow-fed control values.
      Insulin-induced phosphorylation of Akt and Erk in adipose tissues, skeletal
      muscles, and liver was greatly attenuated in HFHS rats as compared with chow-fed
      controls. High-fat/high-sucrose diet-induced insulin resistance was also
      confirmed in isolated hepatocytes. Fish oil intake prevented insulin resistance
      by improving or fully restoring insulin signaling responses in all tissues and
      isolated hepatocytes. Argan oil intake also improved insulin-dependent
      phosphorylations of Akt and Erk; and in adipose tissue, these responses were
      increased even beyond values observed in chow-fed controls. Taken together, these
      results strongly support the beneficial action of FO on diet-induced insulin
      resistance and glucose intolerance, an effect likely explained by the ability of
      FO to prevent HFHS-induced adiposity. Our data also show for the first time that
      AO can improve some of the metabolic and insulin signaling abnormalities
      associated with HFHS feeding.

PMID- 19394056
TI  - Enhanced methylglyoxal formation in the erythrocytes of hemodialyzed patients.
AB  - Methylglyoxal (MG) contributes significantly to the carbonyl stress in uremia;
      however, the reason for its increased concentration is not clear. Thus, the
      present study was aimed to investigate the formation and degradation of MG in the
      erythrocytes of hemodialyzed (HD) patients with end-stage renal disease. In 22
      nondiabetic patients on long-term HD, erythrocyte MG and d-lactate levels,
      glyoxalase activities, and whole blood reduced glutathione content were
      determined. The data were compared with those from 22 healthy controls.
      Erythrocyte MG and d-lactate production were also investigated in vitro under
      normoglycemic (5 mmol/L) and hyperglycemic (50 mmol/L) conditions. The
      erythrocyte MG levels were elevated (P < .001) in the HD patients. The blood
      reduced glutathione content and glyoxalase I activity were similar to the control
      levels, but the glyoxalase II activity was significantly (P < .005) increased. In
      the normoglycemic in vitro model, production of both MG (P < .001) and d-lactate
      (P < .002) was significantly enhanced in the HD erythrocytes relative to the
      controls. During hyperglycemia, the MG formation and degradation rates were
      further increased (P < .001). The present study demonstrated an increased
      formation of MG in the erythrocytes of HD patients. This seemed to be related to
      a glucose metabolism disturbance of the cells. The degradation system of MG was
      also activated; still, it was not able to counteract the high rate of MG
      formation. The alterations and imbalance of these metabolic processes may
      contribute to the carbonyl overload and stress in the HD patients.

PMID- 19394057
TI  - Cytosolic heteroglycans in photoautotrophic and in heterotrophic plant cells.
AB  - In plants several 'starch-related' enzymes exist as plastid- and cytosol-specific
      isoforms and in some cases the extraplastidial isoforms represent the majority of
      the enzyme activity. Due to the compartmentation of the plant cells, these
      extraplastidial isozymes have no access to the plastidial starch granules and,
      therefore, their in vivo function remained enigmatic. Recently, cytosolic
      heteroglycans have been identified that possess a complex pattern of the monomer
      composition and glycosidic bonds. The glycans act both as acceptors and donors
      for cytosolic glucosyl transferases. In autotrophic tissues the heteroglycans are
      essential for the nocturnal starch-sucrose conversion. In this review we
      summarize the current knowledge of these glycans, their interaction with glucosyl
      transferases and their possible cellular functions. We include data on the
      heteroglycans in heterotrophic plant tissues and discuss their role in
      intracellular carbon fluxes that originate from externally supplied
      carbohydrates.

PMID- 19394058
TI  - Diagnostic accuracy of nitrite dipstick testing for the detection of bacteriuria
      of pregnancy.

PMID- 19394059
TI  - Exhaled breath condensate hydrogen peroxide and pH for the assessment of lower
      airway inflammation in the horse.
AB  - Measurement of hydrogen peroxide (H(2)O(2)) concentration and pH in exhaled
      breath condensate (EBC) is useful for detection and monitoring of asthma in
      humans. In contrast, limited information on the use of these parameters for the
      investigation of lower airway inflammation (LAI) is available for horses. Aims of
      the current study were to investigate the intra- and inter-day variations of EBC
      H(2)O(2) concentration and pH in horses and establish any relationship(s) with
      LAI. Both intra- and inter-day variability of EBC H(2)O(2) concentration were
      large, while those of pH were small. No significant difference in the intra-day
      or inter-day H(2)O(2) concentrations or pH measurements were found in control or
      LAI horses, except for inter-day H(2)O(2) concentration in horses with LAI
      (p=0.019). There was no significant difference in EBC pH or H(2)O(2)
      concentration between control and LAI horses, however a trend for a reduced pH in
      horses with LAI was observed.

PMID- 19394060
TI  - [Diagnostic criteria for mild cognitive impairment in a cohort of 100 subjects].
AB  - INTRODUCTION: Tracking can be proposed for subjects with prodromal sates of
      Alzheimer disease (AD) or people with mild cognitive impairment (MCI) at risk to
      develop dementia who present a memory complaint. PATIENTS AND METHODS: We present
      a cohort of 100 subjects who attended a French memory unit with a diagnostic of
      MCI. We applied the different definitions used in daily practice. We used the
      following diagnostic criteria: amnestic MCI (MCIa), multiple domain impairment
      (MDI), single non-memory dysfunction impairment (SDI), and prodromal Alzheimer's
      disease (Prod-AD), using only the neuropsychological episodic memory criteria. We
      also analyzed the population of subjects presenting MCI and vascular risk
      factors. RESULTS: Ninety-nine subjects met the criteria of MCIa, 43 met the
      criteria of isolated MCIa; 56 met the criteria of MDI; one met the criteria of
      SDI; 40 met the criteria of MAPD; 58 met the criteria of MCI with vascular risk
      factors. DISCUSSION: Using the diagnostic criteria of MCI can lead to clinical
      ambiguity because the population recruited on the bases of memory complaint is
      highly variable. Moreover, many subjects meet many definitions. This overlap of
      the classifications further complicates the decision to favor one criterion over
      another. In clinical practice, a classification system using the concepts of MCI,
      MDI and SDI seems to be quite operational but cut-offs are necessary for the
      tests applied, in addition to a clarified choice of which tests to use.

PMID- 19394061
TI  - Recognition of dengue NS1 antigen and compulsory case reporting.

PMID- 19394062
TI  - Epstein-Barr virus nuclear antigen 3C targets p53 and modulates its
      transcriptional and apoptotic activities.
AB  - The p53 tumor suppressor gene is one of the most commonly mutated genes in human
      cancers and the corresponding encoded protein induces apoptosis or cell-cycle
      arrest at the G1/S checkpoint in response to DNA damage. To date, previous
      studies have shown that antigens encoded by human tumor viruses such as SV40
      large T antigen, adenovirus E1A and HPV E6 interact with p53 and disrupt its
      functional activity. In a similar fashion, we now show that EBNA3C, one of the
      EBV latent antigens essential for the B-cell immortalization in vitro, interacts
      directly with p53. Additionally, we mapped the interaction of EBNA3C with p53 to
      the C-terminal DNA-binding and the tetramerization domain of p53, and the region
      of EBNA3C responsible for binding to p53 was mapped to the N-terminal domain of
      EBNA3C (residues 130-190), previously shown to interact with a number of
      important cell-cycle components, specifically SCF(Skp2), cyclin A, and cMyc.
      Furthermore, we demonstrate that EBNA3C substantially represses the
      transcriptional activity of p53 in luciferase based reporter assays, and rescues
      apoptosis induced by ectopic p53 expression in SAOS-2 (p53(-/-)) cells.
      Interestingly, we also show that the DNA-binding ability of p53 is diminished in
      the presence of EBNA3C. Thus, the interaction between the p53 and EBNA3C provides
      new insights into the mechanism(s) by which the EBNA3C oncoprotein can alter
      cellular gene expression in EBV associated human cancers.

PMID- 19394063
TI  - The origin and global emergence of adamantane resistant A/H3N2 influenza viruses.
AB  - Resistance to the adamantane class of antiviral drugs by human A/H3N2 influenza
      viruses currently exceeds 90% in the United States and multiple Asian countries.
      Adamantane resistance is associated with a single amino acid change (S31N) in the
      M2 protein, which was shown to rapidly disseminate globally in 2005 in
      association with a genome reassortment event. However, the exact origin of
      influenza A/H3N2 viruses carrying the S31N mutation has not been characterized,
      particularly in South-East Asia. We therefore conducted a phylogenetic analysis
      of the HA, NA, and M1/2 segments of viral isolates collected between 1997 and
      2007 from temperate localities in the Northern hemisphere (New York State, United
      States, 492 isolates) and Southern hemisphere (New Zealand and Australia, 629
      isolates) and a subtropical locality in South-East Asia (Hong Kong, 281
      isolates). We find that although the S31N mutation was independently introduced
      at least 11 times, the vast majority of resistant viruses now circulating
      globally descend from a single introduction that was first detected in the summer
      of 2003 in Hong Kong. These resistant viruses were continually detected in Hong
      Kong throughout 2003-2005, acquired a novel HA through reassortment during the
      first part of 2005, and thereafter spread globally. The emergence and persistence
      of adamantane resistant viruses in Hong Kong further supports a source-sink model
      of global influenza virus ecology, in which South-East Asia experiences
      continuous viral activity and repeatedly seeds epidemics in temperate areas.

PMID- 19394064
TI  - Differential patterns of immune escape at Tat-specific cytotoxic T cell epitopes
      in pigtail macaques.
AB  - Cytotoxic T lymphocyte responses to conserved proteins such as Gag within HIV- or
      SIV-infected hosts can facilitate partial control of viremia. However, the
      utility of targeting variable viral proteins by CTL responses is unclear. We
      studied CTL responses to regulatory and accessory proteins of SIV in pigtail
      macaques. The regulatory and accessory proteins were the most commonly targeted
      proteins by CTL responses from pigtail macaques. We identified 2 novel Tat
      specific CTL responses that were both restricted by the Mane-A10 allele. Viral
      escape at one of the Tat epitopes, KSA10, was slower in comparison to another Tat
      epitope KVA10. The kinetics of escape of the KSA10 Tat epitope were more similar
      to an immunodominant KP9 Gag epitope also restricted by Mane-A10. Our results
      suggest that some regulatory or accessory CTL epitopes may be useful targets for
      vaccination against HIV.

PMID- 19394065
TI  - EBV BMRF-2 facilitates cell-to-cell spread of virus within polarized oral
      epithelial cells.
AB  - We previously reported that the Epstein-Barr virus (EBV) BMRF-2 protein plays an
      important role in EBV infection of polarized oral epithelial cells by interacting
      with beta1 and alphav family integrins. Here we show that infection of polarized
      oral epithelial cells with B27-BMRF-2(low) recombinant virus, expressing a low
      level of BMRF-2, resulted in significantly smaller plaques compared with
      infection by parental B95-8 virus. BMRF-2 localized in the trans-Golgi network
      (TGN) and basolateral sorting vesicles and was transported to the basolateral
      membranes of polarized epithelial cells. Mutation of the tyrosine- and dileucine
      containing basolateral sorting signal, YLLV, in the cytoplasmic domain of BMRF-2
      led to the failure of its accumulation in the TGN and its basolateral transport.
      These data show that BMRF-2 may play an important role in promoting the spread of
      EBV progeny virions through lateral membranes of oral epithelial cells.

PMID- 19394066
TI  - Comment on: "Modelling the PAO-GAO competition: effects of carbon source, pH and
      temperature" by Lopez-Vazquez, C.M., Oehmen, A., Hooijmans, C.M., Brdjanovic, D.,
      Gijzen, H.J., Yuan, Z., van Loosdrecht, M..C.M. Water Res. (2009).

PMID- 19394067
TI  - Assessment of polybrominated diphenyl ethers (PBDEs) in samples collected from
      indoor environments in South East Queensland, Australia.
AB  - Polybrominated diphenyl ethers (PBDEs) are compounds that are used as flame
      retardants. Human exposure is suggested to be via food, dust and air. An
      assessment of PBDE exposure via indoor environments using samples of air, dust
      and surface wipes from eight sites in South East Queensland, Australia was
      conducted. For indoor air, SigmaPBDEs ranged from 0.5-179 pg/m(3) for homes and
      15-487 pg/m(3) for offices. In dust, SigmaPBDEs ranged from 87-733 ng/g dust and
      583-3070 ng/g dust in homes and offices, respectively. PBDEs were detected on 9
      out of 10 surfaces sampled and ranged from non-detectable to 5985 pg/cm(2).
      Overall, the congener profiles for air and dust were dominated by BDE-209. This
      study demonstrated that PBDEs are ubiquitous in the indoor environments of
      selected buildings in South East Queensland and suggest the need for detailed
      assessment of PBDE concentrations using more sites to further investigate the
      factors influencing PBDE exposure in Australia.

PMID- 19394069
TI  - Sediment mercury dynamics and historical trends of mercury deposition in the St.
      Lawrence River area of concern near Cornwall, Ontario, Canada.
AB  - The St. Lawrence River near Cornwall, Ontario was designated an Area of Concern
      by the International Joint Commission in 1985. Sediments from this area have
      historically been contaminated with mercury (Hg), and although concentrations
      have decreased since the 1970s, they still remain high. Nine sediment cores were
      collected from three sites within the Area of Concern in 2004/05 to determine the
      variability in historical profiles of Hg deposition to the river. Sediment and
      pore water phases were analyzed for total mercury (THg) and methyl mercury (MeHg)
      and cores were analyzed for 210Pb to determine chronologies of sedimentation at
      these sites. Mercury diffusion rates in pore waters within the sediment column
      were determined to be very low (between 0 and 2.15 ng cm(-2) year(-1), n = 3)
      compared to the recent Hg sedimentation rates at these sites (183+/- 30 ng cm(-2)
      year(-1) SE, n = 9) determined by multiplying surface Hg concentrations with
      210Pb-derived sedimentation rates. These results indicate that Hg profiles in
      these cores accurately depict historical releases of Hg to the river bed. The
      influence of federal regulations in the early 1970s to restrict Hg emissions to
      the river was apparent in these dated sediment cores, as were the closures of
      several local industries in the mid 1990s. Mercury accumulation rates prior to
      1970 were 60 times higher than those occurring after 1995. Methyl mercury showed
      surface enrichment in most of these sediment cores providing evidence that
      mercury methylation occurred most rapidly near the sediment surface.

PMID- 19394070
TI  - Microbial community structure and dynamics in a pilot-scale submerged membrane
      bioreactor aerobically treating domestic wastewater under real operation
      conditions.
AB  - A pilot scale submerged ultra-filtration membrane bioreactor (MBR) was used for
      the aerobic treatment of domestic wastewater over 9 months of year 2006 (28th
      March to 21st December). The MBR was installed at a municipal wastewater facility
      (EMASAGRA, Granada, Spain) and was fed with real wastewater. The experimental
      work was divided in 4 stages run under different sets of operation conditions.
      Operation parameters (total and volatile suspended solids, dissolved oxygen
      concentration) and environmental variables (temperature, pH, COD and BOD(5) of
      influent water) were daily monitored. In all the experiments conducted, the MBR
      generated an effluent of optimal quality complying with the requirements of the
      European Law (91/271/CEE 1991). A cultivation-independent approach (polymerase
      chain reaction-temperature gradient gel electrophoresis, PCR-TGGE) was used to
      analyze changes in the structure of the bacterial communities in the sludge.
      Cluster analysis of TGGE profiles demonstrated significant differences in
      community structure related to variations of the operation parameters and
      environmental factors. Canonical correspondence analysis (CCA) suggested that
      temperature, hydraulic retention time and concentration of volatile suspended
      solids were the factors mostly influencing community structure. 23 prominent TGGE
      bands were successfully reamplified and sequenced, allowing gaining insight into
      the identities of predominantly present bacterial populations in the sludge.
      Retrieved partial 16S-rRNA gene sequences were mostly related to the alpha
      Proteobacteria, beta-Proteobacteria and gamma-Proteobacteria classes. The
      community established in the MBR in each of the four stages of operation
      significantly differed in species composition and the sludge generated displayed
      dissimilar rates of mineralization, but these differences did not influence the
      performance of the bioreactor (quality of the permeate). These data indicate that
      the flexibility of the bacterial community in the sludge and its ability to get
      adapted to environmental changes play an important role for the stable
      performance of MBRs.

PMID- 19394071
TI  - Simultaneous toxic action of zinc and alachlor resulted in enhancement of zinc
      uptake by the filamentous fungus Paecilomyces marquandii.
AB  - Microbial ability vary when pollutants exist together in the environment in
      comparison to the presence of single toxic compound. The influence of alachlor
      and zinc on the growth of the filamentous fungus Paecilomyces marquandii and its
      ability to eliminate alachlor and zinc has been studied. Their simultaneous
      presence in the polluted environment is very probable. In liquid cultures the
      pesticide (50 mg/l) was removed with the efficiency of 85% within 7 days.
      Beginning from the third day of culturing two derivatives of alachlor were found:
      N-(2',6'-diethylphenyl)-N-metoxymethyl-acetamide and unstable 2-chloro-N-(2',6'
      diethylphenyl)-N-hydroxymethyl-acetamide, the first time detected as product of
      alachlor metabolisation by filamentous fungus. The herbicide elimination was not
      inhibited by zinc up to 1.0 mM of the metal content in the culture medium, 5.0
      7.5 mM of the metal limited alachlor depletion by 30-50%, whereas a higher zinc
      concentration stopped this process. Zinc content in P. marquandii mycelium during
      the incubation in growth medium reached 10-20 mg/g of dry weight and was
      increased up to 99 mg/g by alachlor, however due to its presence a strong
      inhibitory effect on growth was observed. It was postulated that the increase in
      zinc binding by the growing mycelium of P. marquandii in the presence of the
      pesticide was connected with the changes in the wall and membrane composition
      induced by simultaneous toxic interaction of zinc and alachlor. Only 15-20% of
      bound zinc was detected in the cell wall of the fungus, whereas the amount of
      zinc loaded in the wall of mycelium originating from the cultures incubated in
      the alachlor presence increased to 60%. Additionally, changes in the profile of
      fatty acids of cultures with pesticide and metal addition were observed. P.
      marquandii strain seems to be promising for a potential industrial application.
      It can both effectively bind zinc and remove alachlor from the mixture of
      pollutants.

PMID- 19394072
TI  - Comparison of gonadorelin products in lactating dairy cows: efficacy based on
      induction of ovulation of an accessory follicle and circulating luteinizing
      hormone profiles.
AB  - This study evaluated whether the four gonadorelin products that are commercially
      available in the United States produce comparable ovulation responses in
      lactating cows. Dairy cows at 7 d after last gonadotropin-releasing hormone
      (GnRH) treatment of Ovsynch (Day 7), with a corpus luteum (CL) > or =15 mm and at
      least one follicle > or =10mm, were evaluated for response to GnRH treatment.
      Selected cows were randomized to receive (100 microg; im): (1) Cystorelin
      (n=146); (2) Factrel (n=132); (3) Fertagyl (n=140); or (4) Ovacyst (n=140). On
      Day 14, cows were examined for ovulation by detection of an accessory CL.
      Circulating luteinizing hormone (LH) concentrations were also evaluated in some
      cows after treatment with 100 microg (n=10 per group) or 50 microg (n=5 per
      group) GnRH. Statistical analyses were performed with the procedures MIXED and
      GLIMMIX of the SAS program. Percentage of cows ovulating differed (P<0.01) among
      groups, with that for Factrel being lower (55.3%) than that for Cystorelin
      (76.7%), Fertagyl (73.6%), or Ovacyst (85.0%). There was no effect of batch,
      parity, or follicle size on ovulation response, but increasing body condition
      score decreased ovulation response. There was a much greater LH release in cows
      treated with 100 microg than in those treated with 50 microg, but there were no
      detectable differences among products in time to LH peak, peak LH concentration,
      or area under the LH curve and no treatment effects nor treatment by time
      interactions on circulating LH profile. Thus, ovulation response to Factrel on
      Day 7 of the cycle was lower than that for other commercial GnRH products,
      although a definitive mechanism for this difference between products was not
      demonstrated.

PMID- 19394073
TI  - Lectin-binding sites in isolated equine cumulus-oocyte complexes: differential
      expression of glycosidic residues in complexes recovered with compact or expanded
      cumulus.
AB  - Equine cumulus-oocyte complexes (COCs) were analyzed by means of 13 lectins to
      evaluate their glycoconjugate patterns and to verify differences between COCs
      recovered with compact (Cp) and expanded (Exp) cumulus. Cumulus cells showed a
      similar staining pattern in both Cp and Exp COCs with all lectins used, except
      for a higher reactivity with SNA and GSA II in Cp COCs and SBA in Exp COCs. The
      zona pellucida (ZP) showed (1) uniform staining with MAL II, RCA(120), and SBA in
      both Cp and Exp COCs, (2) trilaminar binding pattern with WGA as well as higher
      Con A reactivity in the outer region of both types of COCs, (3) uniform staining
      with PNA only in Exp COCs, (4) uniform and trilaminar binding pattern with SNA in
      Cp and Exp COCs, respectively, and (5) major reactivity with GSA II in Exp COCs.
      Ooplasm showed similar staining intensity with Con A, HPA, GSA I-B(4), and WGA in
      both Cp and Exp COCs, with stronger reactivity to GSA II in Exp COCs, whereas
      SNA, UEA I, and LTA binding sites were present only in Cp COCs. Oocyte cortical
      granules of both Cp and Exp COCs reacted with Con A and WGA. These results
      suggest that, in the mare, viable (Cp) and atretic (Exp) COCs display different
      glycoconjugate staining pattern, which may account for the different maturation
      and developmental competence of COCs.

PMID- 19394074
TI  - Freeze-dried acellular dermal matrix graft: effects of rehydration on physical,
      chemical, and mechanical properties.
AB  - OBJECTIVES: To test the effect of rehydration time over the range prescribed in
      the manufacturer's protocol on (1) the biomechanical properties and on (2) the
      recovery and stabilization of the collagenous matrix of AlloDerm. METHODS: A
      sterile dish containing warm saline solution was prepared, and samples rehydrated
      for 5 min. Subsequently, three other dishes with the solution were prepared and
      samples assigned into three groups according to the total rehydration time: 10
      min (G1), 20 min (G2), and 40 min (G3). Uni-axial tensile testing was used to
      assess the biomechanical properties of the different groups and the control (dry
      condition). Physico-chemical properties were examined by Fourier transform
      infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) as a
      function of rehydration time. RESULTS: ANOVA revealed a significant change in
      tensile strength (p=0.0269) and in elastic modulus (p=0.0306) for AlloDerm
      following different rehydration times. The lowest tensile strength was in the dry
      condition, whereas the highest was achieved after a 40 min rehydration. The
      shortest rehydration periods did not result in a statistically significant
      (p>0.05) change in elastic modulus. However, after 40 min the elastic modulus
      increased significantly when compared to the shortest periods. FT-IR confirmed
      the protein backbone recovery of the graft matrix after rehydration. DSC scans of
      rehydrated samples showed visible shifts in the denaturation temperature to
      higher values compared to as-received sample (dry) suggesting stronger polymer
      water bridge formation, supporting the increase in the biomechanical properties.
      SIGNIFICANCE: The current study suggests that there are major changes on the
      biomechanical properties of the collagenous graft as rehydration time increases,
      which were also structurally confirmed by the physico-chemical analyses.
      Clinicians must be aware that the rehydration times of the manufacturer's
      protocol result in a significant range in mechanical and physico-chemical
      properties. Therefore, a rehydration time of at least 20 min guarantees not only
      better handling and mechanical properties but, most importantly, supplies a
      material that closely resembles the natural tissue.

PMID- 19394075
TI  - The decade of NICE.

PMID- 19394076
TI  - Clinical experts or methodologists to write clinical guidelines?

PMID- 19394077
TI  - If NICE was in the USA.

PMID- 19394078
TI  - The controlled presentation of TGF-beta1 to hepatocytes in a 3D-microfluidic cell
      culture system.
AB  - 3D-microfluidic cell culture systems (3D-microFCCSs) support hepatocyte functions
      in vitro which can be further enhanced by controlled presentation of 100-200
      pg/ml TGF-beta1, thus mimicking the roles of supporting cells in co-cultures.
      Controlled presentation of TGF-beta1 is achieved by either direct perfusion or in
      situ controlled release from gelatin microspheres immobilized in the 3D
      microFCCS. Primary hepatocytes cultured for 7 days with the in situ controlled
      released TGF-beta1 exhibited up to four-fold higher albumin secretion and two
      fold higher phase I/II enzymatic activities, significantly improving the
      sensitivity of hepatocytes to acetaminophen-mediated hepatotoxicity, compared to
      hepatocytes cultured with directly perfused TGF-beta1 or without TGF-beta1. The
      controlled presentation of TGF-beta1 enhanced hepatocyte functions in
      microfluidic systems without the complications of co-cultures, allowing for
      simplifications in drug testing and other hepatocyte-based applications.

PMID- 19394079
TI  - Enhanced dermal wound neovascularization by targeted delivery of endothelial
      progenitor cells using an RGD-g-PLLA scaffold.
AB  - Endothelial progenitor cells (EPCs), endothelial precursors that promote
      neovascularization in ischemic tissues, have shown the limited vascular
      regeneration efficacy due to their poor homing into injured sites and low
      survival, so that a variety of biosynthetic scaffolds have been employed as cell
      delivery vehicles to overcome the current cell transplantation methods. However,
      few paralleled studies that directly compare the efficacy of EPCs seeded within
      synthetic scaffolds to that of EPCs delivered by the conventional transplantation
      techniques used for EPC therapies have been performed. To address these issues,
      RGD-g-PLLA biosynthetic scaffold was developed for the targeted EPC delivery and
      was found to successfully support the in vitro growth and endothelial functions
      of EPCs. This scaffold also appeared to be good as in vivo targeted delivery
      carriers of EPCs as it promoted vascular regeneration in a murine dermal wound
      models. Furthermore, direct comparison with the intradermal EPC injection
      revealed that the targeted delivery of EPCs by using the RGD-g-PLLA scaffold was
      superior to their conventional local injection method in terms of the
      localization and survival/retention of the transplanted EPCs, and their vascular
      repairing potential. These results suggest that the development of an effective
      stem cell delivery system may help to maximize the tissue-repairing efficacy with
      a limited number of stem cells, thereby resolving the limited clinical success of
      current stem cell therapies that have utilized simple cell injections or
      infusions.

PMID- 19394081
TI  - Key role of a PtdIns-4,5P2 micro domain in ionic regulation of the mammalian
      heart Na+/Ca2+ exchanger.
AB  - Phosphatidylinositol biphosphate (PtdIns-4,5P(2)) plays a key role in the
      regulation of the mammalian heart Na(+)/Ca(2+) exchanger (NCX1) by protecting the
      intracellular Ca(2+) regulatory site against H(+)(i) and (H(+)(i)+Na(+)(i))
      synergic inhibition. MgATP and MgATP-gamma-S up-regulation of NCX1 takes place
      via the production of this phosphoinositide. In microsomes containing PtdIns
      4,5P(2) incubated in the absence of MgATP and at normal [Na(+)](i),
      alkalinization increases the affinity for Ca(2+)(i) to the values seen in the
      presence of the nucleotide at normal pH; under this condition, addition of MgATP
      does not increase the affinity for Ca(2+)(i) any further. On the other hand,
      prevention of Na(+)(i) inhibition by alkalinization in the absence of MgATP does
      not take place when the microsomes are depleted of PtdIns-4,5P(2). Experiments on
      NCX1-PtdIns-4,5P(2) cross-coimmunoprecipitation show that the relevant PtdIns
      4,5P(2) is not the overall membrane component but specifically that tightly
      attached to NCX1. Consequently, the highest affinity of the Ca(2+)(i) regulatory
      site is seen in the deprotonated and PtdIns-4,5P(2)-bound NCX1. Confirming these
      results, a PtdIns-5-kinase also cross-coimmunoprecipitates with NCX1 without
      losing its functional competence. These observations indicate, for the first
      time, the existence of a PtdIns-5-kinase in the NCX1 microdomain.

PMID- 19394080
TI  - Placental pathologies in fetal MRI with pathohistological correlation.
AB  - INTRODUCTION: The purpose of this study was to evaluate whether currently
      available fetal Magnetic Resonance Imaging (MRI/MR) techniques are sufficient for
      the assessment of placental pathologies. We hypothesized that placental
      pathologies as detected and evaluated by MRI, would correlate with histological
      findings. PATIENTS AND METHODS: In a retrospective study, 45 singleton
      pregnancies from 19 to 35 gestational weeks, with placental pathologies on MR
      scans, were included. MRI was performed on a 1.5T unit using T2-, T1-, and
      diffusion-weighted and echo-planar sequences. Pathologies were categorized into
      infarction with/without hemorrhagic components, subchorionic/intervillous
      thrombi/hemorrhages, retroplacental hematoma, massive perivillous fibrin
      deposition, and chorioamnionitis. Pathohistological examination was performed
      postnatally within a median of seven days between MR examination and delivery.
      RESULTS AND DISCUSSION: Pathologically, 26 placentas showed infarctions (96.2% on
      MR scans), two retroplacental hematomas were detected by MRI and confirmed by
      pathology, and 9 of 14 subchorionic hematomas were confirmed. Six of eight
      intervillous hemorrhages were seen on MRI, and three of six cases of severe
      chorioamnionitis were diagnosed prenatally. Placental hemorrhages (retroplacental
      hematoma, intervillous thrombi, subchorionic hematoma), and ischemic lesions
      could be detected with fetal MRI, while chorioamnionitis and even massive
      perivillous fibrin deposition showed few signal changes, probably reflecting
      small macroscopic changes in the placenta. Fetal MRI, therefore, seems to be a
      promising tool for the assessment of placental insufficiency.

PMID- 19394082
TI  - SDF1/CXCL12 (-801GA) polymorphism is a prognostic factor after treatment
      initiation in Waldenstrom macroglobulinemia.
AB  - The interaction of the chemokine CXCL12 with CXCR4 regulates homing of tumoral
      cells in bone marrow in Waldenstrom macroglobulinemia (WM). We assessed the
      distribution and the clinical influence of the CXCL12 (-801GA) polymorphism using
      PCR RFLP in a series of 114 WM patients. CXCL12 (-801AA) genotype was more
      frequent in WM patients compared with control subjects (p = 0.01). On the other
      hand, CXCL12 (-801GG) patients had a shorter median survival after initiation of
      first line therapy than remaining patients (p = 0.01). In conclusion, the CXCL12
      (-801GA) polymorphism may either be associated with a high incidence of WM or
      influence clinical outcome.

PMID- 19394083
TI  - Upregulation of stem cell genes in multidrug resistant K562 leukemia cells.
AB  - The transmembrane transporter P-glycoprotein (P-gp) encoded by ABCB1, is one
      major cause for multidrug resistance (MDR). We compared the genomic profile and
      gene expression pattern of the P-gp positive K562VCR cells with parental P-gp
      negative K562wt cells. In K562VCR array CGH revealed amplification of ABCB1,
      ABCB4, ABCB5 and SEMA3D, whereas expression microarrays demonstrated upregulation
      of stem cell genes (e.g. KIT and HOXB4), anti-apoptotic genes (e.g. IGF1R and
      CCNG1), and downregulation of pro-apoptotic genes (e.g. CASP4, 6 and 7). Thus,
      K562VCR cells disclose stem cell characteristics including a range of drug
      resistance mechanisms possibly attained as a stem cell program switched on en
      bloc.

PMID- 19394084
TI  - External exposure and bioaccumulation of PCBs in humans living in a contaminated
      urban environment.
AB  - Humans are exposed to different mixtures of PCBs depending on the route of
      exposure. In this study we investigated the potential contribution of inhalation
      to the overall human exposure to PCBs in an urban area. For this purpose, the
      mechanistically based, non-steady state bioaccumulation model ACC-HUMAN was
      applied to predict the PCB body burden in an adult living in the Midwestern
      United States who eats a typical North American diet and inhales air contaminated
      with PCBs. Dietary exposure was estimated using measured data for eighteen PCB
      congeners in different food groups (fish, meat and egg, dairy products). Two
      scenarios for inhalation exposure were evaluated: one using air concentrations
      measured in Chicago, and a second using air measurements in a remote area on Lake
      Michigan, Sleeping Bear Dunes. The model predicted that exposure via inhalation
      increases the accumulated mass of PCBs in the body by up to 30% for lower
      chlorinated congeners, while diet is by far the dominant source of exposure for
      those PCB congeners that accumulate most in humans.

PMID- 19394085
TI  - Mitigation of arsenic contamination in irrigated paddy soils in South and South
      East Asia.
AB  - It has recently become apparent that arsenic-contaminated groundwater used for
      irrigation in several countries of South and South-east Asia is adding arsenic to
      soils and rice, thus posing a serious threat to sustainable agricultural
      production and to the health and livelihoods of affected people in those
      countries. This paper describes the many environmental, agricultural and social
      factors that determine practical mitigation strategies and research needs, and
      describes possible mitigation measures that need to be tested. These measures
      include providing alternative irrigation sources, various agronomic measures, use
      of soil amendments, growing hyperaccumulator plants, removing contaminated soil
      and using alternative cooking methods.

PMID- 19394086
TI  - Higher psychological pain during a major depressive episode may be a factor of
      vulnerability to suicidal ideation and act.
AB  - BACKGROUND: It has been suggested that psychological pain ("psychache") is a key
      factor in the suicidal process. In addition, suicidal acts may be best understood
      within a stress-vulnerability model. We hypothesized that more intense psychache
      during a major depressive episode would be a factor of vulnerability to suicidal
      behavior. METHODS: Patients hospitalized for a major depressive episode,
      including 87 individuals with a recent history of suicidal acts, 61 individuals
      with a past history of suicidal acts, and 62 individuals without any suicidal
      history, were assessed at admission using several Visual Analog scales to measure
      levels of psychache, physical pain and suicidal ideation. RESULTS: Patients with
      a recent or past history of suicide attempts expressed significantly higher
      levels of current psychological pain, and a higher intensity and frequency of
      current suicidal ideation than patients without any history of suicidal acts. The
      level of current psychache was significantly and positively associated with
      intensity and frequency of suicidal ideation. There were no between-group
      differences for physical pain. LIMITATIONS: Medication status was not controlled.
      A lack of statistical power may have masked an association between physical pain
      and suicidal ideation. CONCLUSIONS: Higher psychological pain during a major
      depressive episode may be a factor of vulnerability to suicidal behavior, by
      increasing the propensity to suicidal ideation. Measuring and taking care of
      psychache during a depressive episode should be a major therapeutic target during
      crisis intervention.

PMID- 19394088
TI  - Social anxiety disorder in older adults: evidence from the National Epidemiologic
      Survey on alcohol and related conditions.
AB  - OBJECTIVE: This study aims to investigate the following: 1) the association of
      social anxiety disorder with childhood parental loss and recent stressful life
      events; 2) the coexistence of social anxiety disorder and major depressive
      disorders (MDD); and 3) the impact of social anxiety disorder on medical
      conditions, obesity, health service utilization, and health-related quality of
      life. DESIGN: Cross-sectional observational study. SETTING: The National
      Epidemiologic Survey on Alcohol and Related Conditions (2001-2002), a national
      representative survey of the U.S. noninstitutionalized household population.
      PARTICIPANTS: 13,420 respondents aged 55 and above. MEASUREMENTS: Social anxiety
      disorder was assessed using the Alcohol Use Disorder and Associated Disabilities
      Interview Schedule-DSM-IV Version (AUDADIS-IV). Demographic characteristics,
      psychosocial risk factors, psychiatric disorders, health-related quality of life,
      obesity, medical conditions, and health service utilization were measured.
      RESULTS: The current and lifetime prevalence rates of specific phobia were found
      to be 1.83% and 3.50%, respectively. Multivariate analyses revealed that social
      anxiety disorder was more common among the younger age groups and those who
      reported stressful life events. In addition, MDD, specific phobia, and
      personality disorder were significantly related to social anxiety disorder.
      Lastly, after adjusting for other psychiatric comorbidities, the association of
      social anxiety disorder with health-related quality of life, medical condition,
      and health care service utilization became insignificant. CONCLUSION: The
      correlation between social anxiety disorder and MDD raises further questions
      about the nature of social anxiety disorder among older adults, but this study
      does not support the notion that this disorder has a strong impact on the quality
      of life in old age independent of other psychiatric comorbidities.

PMID- 19394087
TI  - Appraisals of stressors and common mental disorder from early to mid-adulthood in
      the 1946 British birth cohort.
AB  - BACKGROUND: We examined the extent to which perceived life change following
      experiences of stressful life events, differentiated by type of stressor,
      influenced mental health during adulthood. METHODS: The analytic sample of 2073
      cohort members was drawn from the MRC National Survey of Health and Development,
      a sample followed since their birth in March 1946. Logistic regression was used
      to assess the relationship between stressors reported at 36 and 43 years and
      common mental disorder at 36, 43, and 53 years. Common mental disorder was
      measured using the Present State Exam at 36 years, the Psychiatric Symptom
      Frequency at 43 years, and the 28-item General Health Questionnaire at 53 years.
      RESULTS: Data spanning across nearly 20 years suggest that stressors perceived to
      have contributed to a notable life change increased the likelihood of scoring
      above the cut off score for common mental disorder in comparison to stressors
      experienced without subsequent life change. Models were adjusted for gender,
      educational attainment, social class, relationship status, and past episodes of
      common mental disorder. This relationship appears to be most evident for proximal
      family and economic stressors and distal interpersonal relationship stressors
      experienced by close friends and relatives. LIMITATIONS: All study information is
      based on self-reports and details about the nature of the life change or
      cognitive attribution style were not available. CONCLUSIONS: Appraisals of
      changes following stressful life events may be more important than the occurrence
      of stressors alone in assessing the impact of stressful life events on adult
      mental health.

PMID- 19394089
TI  - Plasma omega-3 and psychological distress among Nunavik Inuit (Canada).
AB  - Marine omega-3 (n-3) fatty acid eicosapentaenoic (EPA) and docosahexaenoic (DHA)
      acids have been associated with beneficial effects in mental health. Cultural and
      social changes have been related to a decline in mental health of the Inuit, but
      the role of diet has received scant attention. We examined the relationship
      between psychological distress (PD) and plasma n-3 among 368 Nunavik Inuit aged
      18-74 years who took part in a survey in 1992. Participants were categorized as
      high-level PD if they scored over the 80th percentile of the PD Index Sante
      Quebec Survey (PDISQS-14), and non-distressed subjects were those who scored less
      than this cutoff. Compared with the non-distressed group, n-3 concentrations in
      the PD group were significantly lower in women but not in men. Compared with the
      lowest tertile of EPA + DHA, the odds ratios for high-level PD among women were
      0.32 (95% CI: 0.13-0.82) for the second, and 0.30 (95% CI: 0.10-0.90) for the
      third tertile, after controlling for confounders. In males, there were no
      significant associations between EPA+DHA and PDISQS-14 scores. Our findings
      suggest that marine n-3 may play a role in PD among Inuit women. The gender
      difference observed in our analysis must be examined more carefully in future
      studies.

PMID- 19394090
TI  - Self-assessment of need for help in patients undergoing psychiatric treatment.
AB  - Needs assessment for patients in mental health care is an important tool. When
      used systematically, needs assessment can improve the quality of care and
      facilitate a process of 'shared decision making' in service provision. A self
      report questionnaire, the Needs Assessment Scale (NAS), was developed for use in
      larger survey samples. The perceived problems of patients and their associated
      need for help were assessed in 22 life areas similar to those of the Camberwell
      Assessment of Need (CAN) interview. In this article, we explore the validity and
      utility of the NAS. For this purpose 305 psychiatric patients completed the NAS
      in a postal survey. The factor structure of the scale shows four subscales. Two
      domains are measured: problem assessment and needs assessment. Patients reported
      a mean number of 4.0 (S.D. 3.5) problem areas and a mean number of 2.4 (S.D. 3.6)
      unmet need areas. Differences between various subgroups (e.g. diagnostic
      categories, treatment setting) and concurrent validity with the CAN are
      discussed. The NAS seems to be sensitive to the perceived needs of patients,
      although those with psychotic disorders tend to under-report unmet need. We
      conclude that the NAS is a useful and feasible instrument in the assessment of
      patients' need for help at a population level.

PMID- 19394091
TI  - Insight into severe mental illness, hope, and quality of life of persons with
      schizophrenia and schizoaffective disorders.
AB  - Controversy exists as to the cognitive, emotional and behavioral consequences of
      lack of insight for persons with schizophrenia. This study tested a mediation
      model of the relations between insight into mental illness, hope, and the aspects
      of quality of life of persons with schizophrenia. According to this model,
      insight into mental illness may impact negatively on the quality of life of
      persons with schizophrenia by reducing these persons' hope. Sixty persons with
      schizophrenia or schizoaffective disorder completed questionnaires that assessed
      their insight, quality of life, and hope. The study's results show that for six
      of seven aspects of quality of life and for general awareness of illness, the
      above-hypothesized mediation model was confirmed. These results suggest that
      increasing the hope of persons with schizophrenia may directly and positively
      increase both their quality of life and the usefulness of their insight into
      their illness.

PMID- 19394092
TI  - Foreign body aspiration in children: the value of diagnostic criteria.
AB  - OBJECTIVE: Foreign body aspiration (FBA) is a serious problem in children. While
      bronchoscopy should be performed in all patients with aspiration; patients
      without aspiration should be carefully excluded to avoid an unnecessary
      bronchoscopy. In this study we analyzed the details of our series, complication
      rates and compared the diagnostic findings between patients with an aspirated FB
      and those without. We also calculated the sensitivities, specificities, positive
      predictive values and negative predictive values of clinical history, symptoms,
      physical examination findings and radiological findings in patients with
      suspected FBA (sFBA). Finally, we evaluated the validity of our bronchoscopy
      indications in these patients. METHODS: We reviewed the data of 207 patients who
      underwent rigid bronchoscopy for sFBA. We used clinical history, symptoms,
      physical examination and radiological findings as diagnostic findings.
      Complication rates in addition to these four diagnostic criteria constitute our
      indications for performing a rigid bronchoscopy. RESULTS: After excluding 15
      patients with radiopaque FB or previous fiberoptic bronchoscopy, 138 of 192
      patients had an aspirated foreign body. The sensitivity and specificity of
      clinical history, symptoms, physical examination findings and radiological
      findings were 90.5% and 24.1%, 97.8% and 7.4%, 96.4% and 46.3, and 71.7% and
      74.1% respectively. There was only one major complication which caused moderate
      neurological sequelae. There was no mortality and no thoracotomy or tracheotomy
      requirement in this group. CONCLUSIONS: While symptoms, physical examination
      findings and clinical history had high sensitivities, radiological findings had
      the highest specificity. Low specificities of clinical history, symptoms and
      physical examination findings were due to our expanded bronchoscopy indication,
      which aimed to include all patients with foreign body aspiration. Our low
      complication rate facilitated the expansion of bronchoscopy indications, even for
      patients with slight clinical suspicion.

PMID- 19394094
TI  - Prevalence of coronary artery disease in asymptomatic patients with abnormal
      intima-media thickness by 64-slice computed tomography.

PMID- 19394093
TI  - Otolaryngologic manifestations of Maffucci's syndrome.
AB  - Maffucci's syndrome is an uncommon congenital disease marked by multiple vascular
      malformations and enchondromas throughout the body. Otolaryngologic
      manifestations are relatively rare but potentially can cause symptoms such as
      respiratory distress and dysphagia if the lesions appear in the upper
      aerodigestive tract or larynx. We report a case of a young woman who demonstrated
      a wide range of head and neck pathology associated with this unique disease,
      including sphenoid enchondroma, bilateral petrous apex lesions, and rarely
      reported laryngeal and hypopharyngeal vascular malformations, over a period of
      nearly 20 years.

PMID- 19394095
TI  - Atrial fibrosis and atrial fibrillation: the role of the TGF-beta1 signaling
      pathway.
AB  - BACKGROUND: Atrial fibrosis concurs with chronic atrial fibrillation (AF), a
      phenomenon that contributes to the resistance to restore and maintain sinus
      rhythm (SR). Fibrogenesis represents a complex process in which the transforming
      growth factor-beta1 (TGF-beta1) pathway may play a major role, e.g. in the
      setting of myocardial infarction. The present study addresses the potential
      contribution of the TGF-beta1 signaling pathway to atrial fibrosis in patients
      with AF. METHODS AND RESULTS: Right atrial appendages of 163 patients were
      excised during heart surgery and grouped according to rhythm (SR vs. AF) and AF
      duration. Five groups were defined: SR, paroxysmal/chronic persistent AF (<6
      months), chronic permanent AF (CAF) of 7-24 months, 25-60 months, and >60 months
      duration. Collagen content of atria, determined morphometrically, revealed a
      steady and significant increase in patients with SR (14.6+/-8.9%) up to patients
      with CAF of >60 months (28.1+/-7.1%). Likewise, expression of TGF-beta1 mRNA and
      protein, TGF-beta-receptor-II protein, profibrotic phospho-Smad-2 and -4 proteins
      increased. However, the TGF-beta(1) effect appeared to decline with increasing AF
      duration, characterized by a decrease in TGF-beta-receptor-I protein, increases
      of TGF-beta inhibiting Smad-7 protein and a reduction of ph-Smad-2. CONCLUSIONS:
      Human atrial fibrogenesis in patients with atrial fibrillation is accompanied by
      a biphasic response, an early increase and later loss of responsiveness to TGF
      beta(1). It appears that fibrosis progresses despite compensatory changes in the
      TGF-beta-signaling pathway. The sequential changes in the contribution of
      different profibrotic processes during the establishment of AF may offer the
      opportunity to selectively interfere with the atrial remodeling process at
      different stages.

PMID- 19394096
TI  - Evaluation of a commercial competitive ELISA for the detection of antibodies to
      Rift Valley fever virus in sera of domestic ruminants in France.
AB  - This paper describes the sensitivity and specificity of a commercial competitive
      ELISA for the detection of antibodies to Rift Valley fever virus (RVFV) from sera
      of French domestic ruminants. Field samples were collected from mainland France
      for the known-negative sera (cattle=191, goats=119, sheep=192) and from ruminants
      of a French overseas territory (Mayotte) for the known-positive sera. A cut-off
      value of 43% was determined for all species, achieving a sensitivity and
      specificity of 100% and a concordance of 100% with the species-specific threshold
      recommended by the manufacturer. Our results demonstrate that this ELISA may be a
      suitable diagnostic tool for disease surveillance programmes and import/export
      veterinary certification of French cattle, goats and sheep.

PMID- 19394097
TI  - Interrogating single proteins through nanopores: challenges and opportunities.
AB  - A single nanopore represents an amazingly versatile single-molecule probe that
      can be employed to reveal several important features of polypeptides, such as
      their folding state, backbone flexibility, mechanical stability, binding affinity
      to other interacting ligands and enzymatic activity. Moreover, groundwork in this
      area using engineered protein nanopores has demonstrated new opportunities for
      discovering the biophysical rules that govern the transport of proteins through
      transmembrane protein pores. In this review, I summarize the current knowledge in
      the field and discuss how nanopore probe techniques will provide a new generation
      of research tools in nanomedicine for quantitatively examining the details of
      complex recognition and, furthermore, will represent a crucial step in designing
      other pore-based nanostructures and high-throughput devices for molecular
      biomedical diagnosis.

PMID- 19394098
TI  - Spread-out antiproton beams deliver poor physical dose distributions for
      radiation therapy.
AB  - BACKGROUND AND PURPOSE: Antiprotons have been suggested as a possibly superior
      modality for radiotherapy, due to the energy released when they annihilate, which
      enhances the Bragg peak and introduces a high-LET component to the dose. Previous
      studies have focused on small-diameter near-monoenergetic antiproton beams. The
      goal of this work was to study more clinically relevant beams. METHODS: We used
      Monte Carlo techniques to simulate 120 and 200 MeV beams of both antiprotons and
      protons of 1 x 1 and 10 x 10 cm(2) areas, impinging on water. RESULTS: An
      annihilating antiproton loses little energy locally; most goes into long-range
      secondary particles. When clinically typical field sizes are considered, these
      particles create a substantial dose halo around the primary field and degrade its
      lateral fall-off. Spreading the dose in depth further intensifies these effects.
      CONCLUSIONS: The physical dose distributions of spread-out antiproton beams of
      clinically relevant size (e.g. 10 x 10 cm(2) area) are substantially inferior to
      those of proton beams, exhibiting a dose halo and broadened penumbra. Studies on
      the value of antiproton beams, taking radiobiological effectiveness into account,
      need to assess such realistic beams and determine whether their inferior dose
      distributions do not undermine the potential value of antiprotons for all but the
      smallest fields.

PMID- 19394099
TI  - Self-controlled concurrent feedback and the education of attention towards
      perceptual invariants.
AB  - The present study investigates the effects of different types of concurrent
      feedback on the acquisition of perceptual-motor skills. Twenty participants
      walked through virtual corridors in which rhythmically opening and closing
      sliding doors were placed. The participants aimed to adjust their walking speed
      so as to cross the doors when the doors were close to their maximal aperture
      width. The highest level of performance was achieved by learners who practiced
      the task with unambiguous self-controlled concurrent feedback, which is to say,
      by learners who could request that feedback at wish. Practice with imposed rather
      than self-controlled feedback and practice without concurrent feedback were shown
      to be less effective. Finally, the way in which the self-controlled concurrent
      feedback was presented was also found to be of paramount importance; if the
      feedback is ambiguous, it may even prevent participants from learning the task.
      Clearly, unambiguous self-controlled feedback can give rise to higher levels of
      performance than other feedback conditions (compared to imposed schedule) but,
      depending on the way it is presented, the feedback can also prevent the
      participants from learning the task. In the discussion it is argued that
      unambiguous self-controlled concurrent feedback allows learners to more rapidly
      educate their attention towards more useful perceptual invariants and to
      calibrate the relation between perceptual invariants and action parameters.

PMID- 19394100
TI  - Changes in grasping kinematics due to different start postures of the hand.
AB  - It was proposed that grasping is a relatively stereotyped movement pattern which
      can be subdivided into the components of manipulation, transport, and orientation
      of the hand. However, it is still a matter of debate whether these components are
      independent of each other. In three experiments we altered the start posture of
      the hand by either changing the size of the start aperture or the orientation of
      the hand prior to movement onset. The variation of the aperture size primarily
      affected the manipulation component of the grip resulting in an overall change of
      the pre-shaping profile. In contrast, an alteration of the start orientation
      affected the manipulation and the transport components to a similar extent. These
      results give further evidence that hand orientation is neither planned nor
      controlled independently from the other movement components. Moreover, when the
      grip had to match specific object properties, adjustments were mainly achieved
      within the first movement part. In contrast, when there were no movement
      constraints the final finger positions were influenced by the initial start
      posture of the hand. We found no evidence for a fixed spatial or temporal
      coupling of the grasp and the transport component in our experiments.

PMID- 19394101
TI  - Introductory note to the Cronobacter special issue.

PMID- 19394102
TI  - The feline calicivirus as a sample process control for the detection of food and
      waterborne RNA viruses.
AB  - Many food and waterborne outbreaks of infectious disease are caused by viruses.
      While numerous methods exist and are being developed to test food and water for
      the presence of enteric viruses, there is no standard control for the comparison
      of different methods. Potential control viruses should be well characterized,
      share the physical characteristics of the enterically infecting viruses and not
      normally be associated with foods. Here, the feline calicivirus (FCV) is proposed
      as a sample process control for methods aimed at the extraction and detection of
      RNA viruses in food and water. FCV is shown to be useful as a control for the
      extraction of hepatitis A virus (HAV) from water using filtration technology and
      from strawberries using the Pathatrix system. The FCV standard provides a
      valuable quality control tool when testing potentially contaminated food samples.

PMID- 19394103
TI  - Operational tolerance after liver transplantation.
AB  - The achievement of an immunosuppression (IS)-free state after transplantation
      represents the ultimate goal of any immunosuppressive regimen. While clinical
      operational tolerance (COT) remains the exception after other types of solid
      organ transplantation, several cases of COT have been described after liver
      transplantation (LT). Overall, the experience gained so far worldwide
      demonstrates that COT can be achieved safely in one quarter of selected
      individuals, irrespective of the immunological background of donor and recipient,
      patient age, indication for LT, study endpoint, length of the weaning period and
      of pre/post-weaning follow-up, presence or not of chimerism. However, most
      transplant physicians still believe that the achievement of COT is still out of
      reach for the majority of LT recipients because of the potential risk for
      transplant survival, the non-randomized nature of most of the studies reported so
      far, and the selective nature of the patients enrolled in such studies, making
      them non-representative of the whole population of LT recipients. Despite these
      concerns, the present article demonstrates that this attitude is potentially no
      longer justified, given the growing evidence that a permanent and stable IS-free
      state can be achieved in a proportion of individuals who have received a LT for
      non-immune mediated liver diseases.

PMID- 19394104
TI  - Marketing and pricing strategies of online pharmacies.
AB  - Internet and e-commerce have profoundly changed society, the economy, and the
      world of health care. The web offers opportunities to improve health, but it may
      also represent a big health hazard since it is a basically unregulated market
      with very low consumer protection. In this paper we analyze marketing and pricing
      strategies of online pharmacies (OPs). Our analysis shows that OPs use strategies
      that would be more suitable for a commodity market than for drugs. These
      strategies differentiate according to variety (brand or generic), quality,
      quantity, and target group. OPs are well aware that the vacuum in the legislation
      allows them to reach a target of consumers that pharmacies cannot normally reach,
      such as those who would like to use the drug without consulting a physician (or,
      even worse, against the physician's advice). In this case, they usually charge a
      higher price, reassure the users by minimizing on the side effects, and induce
      them to bulk purchase through sensible price discounts. This analysis suggests
      that the selling of drugs via the Internet can turn into a "public health risk",
      as has been pointed out by the US Food and Drug Administration.

PMID- 19394105
TI  - Drop-out analysis of community-based health insurance membership at Nouna,
      Burkina Faso.
AB  - OBJECTIVES: This study aims to identify the reasons why enrolled people decide
      not to renew their membership in following years. METHODS: Household survey is
      used to collect information on the factors influencing dropping out from
      community-based health insurance (CBI). Information from CBI agency databank is
      used to describe the general situation of enrolment and drop-out. RESULTS: Since
      the launch of CBI the enrolment rate has been low ranging from 5.2% to 6.3%. The
      drop-out rate, however, has been high ranging from 30.9% to 45.7%. It is found,
      by the multivariate analysis, that female household head, higher age or lower
      education of a household head, lower number of illness episodes in the past three
      months, fewer children or elderly in a household, poor perceived health care
      quality, less seeking care in the past month positively effected on drop-out,
      increasing the rate. However, the household six-month expenditure and the
      distance to the contracted health facility did not have the hypothesised sign. In
      contrast, a higher household expenditure and a shorter distance to the contracted
      health facility increased the drop-out. CONCLUSIONS: High drop-out rates endanger
      the sustainability of CBI not only because they reduce the size of the insurance
      pool, but also because they bear a negative impact on further enrolment and drop
      out. The drop-out rate in the scheme of the Nouna Health District, Burkina Faso,
      is very high. The reasons for drop-out may be related to affordability, health
      needs and health demand, quality of care, household head and household
      characteristics. This study represents a valuable attempt towards further
      increasing the sustainability of CBI schemes, by understanding not what motivates
      people to first enrol in CBI, but what motivates them to renew membership year
      after year.

PMID- 19394106
TI  - Association between general practice referral rates and patients' socioeconomic
      status and access to specialised health care a population-based nationwide study.
AB  - OBJECTIVES: To explore the association between patients' socioeconomic status and
      their referral from general practice to specialised health care. METHODS:
      Multiple regression analysis was used on cross-sectional data on general practice
      referral rates for all Danish general practices in year 2006. RESULTS: Our models
      explained between 26% and 45% of the variation in general practice referral to
      specialised care. Adjusting for access to specialised care (local supply of
      hospitals and practicing specialists) reduced the association between
      socioeconomic factors and referral rates. The results suggest that persons with
      high socioeconomic status are referred more to practicing specialist than persons
      with low socioeconomic status and that the latter are referred more to hospital
      care than the former. CONCLUSIONS: Our results indicate that the influence of
      socioeconomic factors may be overstated failing to control for access to
      specialised care. Still, a socioeconomic gradient was observed in GPs' referral
      pattern to different sorts of health care after adjusting for access. The
      association between socioeconomic status and referral pattern can both be rooted
      in morbidity variation and to the ability of persons with high socioeconomic
      status to influence general practitioners' (GPs') decision making.

PMID- 19394107
TI  - An interactive multiblock approach to meshing the spine.
AB  - Finite element (FE) analysis is a useful tool to study spine biomechanics as a
      complement to laboratory-driven experimental studies. Although individualized
      models have the potential to yield clinically relevant results, the demands
      associated with modeling the geometric complexity of the spine often limit its
      utility. Existing spine FE models share similar characteristics and are often
      based on similar assumptions, but vary in geometric fidelity due to the mesh
      generation techniques that were used. Using existing multiblock techniques, we
      propose mesh generation methods that ease the effort and reduce the time required
      to create subject-specific allhexahedral finite element models of the spine. We
      have demonstrated the meshing techniques by creating a C4-C5 functional spinal
      unit and validated it by comparing the resultant motions and vertebral strains
      with data reported in the literature.

PMID- 19394108
TI  - Impact of high-dose chemotherapy with autologous hematopoietic stem cell
      transplantation on small-cell lung cancer.

PMID- 19394109
TI  - Oral second- and third-line lomustine-etoposide-cyclophosphamide chemotherapy for
      small cell lung cancer.
AB  - PURPOSE: There is no standard therapy for progressive or recurrent small cell
      lung cancer (SCLC). Lomustine, etoposide and cyclophosphamide oral chemotherapy
      were evaluated in a feasibility study of efficacy survival and toxicity. PATIENTS
      AND METHODS: 71 patients were included in this study, 36 in second-line and 35 in
      third-line chemotherapy. They received lomustine (CCNU) 80 or 120mg on D1 only,
      etoposide 100mg from D1 until D6 up to D14 and cyclophosphamide 100mg from D1
      until D6 up to D14 every 4 weeks. The dosages of CCNU and duration of
      administration of the other two drugs were adapted to an original therapeutic
      risk level table on D1 and throughout treatment. Evaluation based on clinical
      status, response and weekly blood counts was performed before each cycle until
      progression. RESULTS: 70 patients were evaluable. They received between 1 and 20
      cycles of treatment (mean=3.7 for second-line and 3.0 for third-line treatment).
      Complete responses were observed for 3 patients in each line, and partial
      responses were noted in 13 patients in second-line and 8 patients in third-line,
      resulting in a total response rate of 27/70=38%. Median-survival time estimated
      from the start of second- or third-line treatment was the same in the two
      subgroups: 4.4 months, but the patients in two subgroups presented different
      clinical characteristics. Haematological toxicity was severe with three toxic
      deaths as frequently observed in this setting, but hospitalisations were uncommon
      during this fully oral treatment that provided a very good quality of life for
      these out-patients. Consumption of health care resources for this low-cost and
      ambulatory treatment was limited. CONCLUSION: The similar efficacy with
      acceptable safety, the ease of administration in out-patients and the economical
      advantages justify comparison of this oral chemotherapy with conventional
      intravenous chemotherapy. A randomised phase II trial is on-going in France for
      second-line SCLC patients on this theme.

PMID- 19394111
TI  - The out-of-hospital validation of the Canadian C-Spine Rule by paramedics.
AB  - STUDY OBJECTIVE: We designed the Canadian C-Spine Rule for the clinical clearance
      of the cervical spine, without need for diagnostic imaging, in alert and stable
      trauma patients. Emergency physicians previously validated the Canadian C-Spine
      Rule in 8,283 patients. This study prospectively evaluates the performance
      characteristics, reliability, and clinical sensibility of the Canadian C-Spine
      Rule when used by paramedics in the out-of-hospital setting. METHODS: We
      conducted this prospective cohort study in 7 Canadian regions and involved alert
      (Glasgow Coma Scale score 15) and stable adult trauma patients at risk for neck
      injury. Advanced and basic care paramedics interpreted the Canadian C-Spine Rule
      status for all patients, who then underwent immobilization and assessment in the
      emergency department to determine the outcome, clinically important cervical
      spine injury. RESULTS: The 1,949 patients enrolled had these characteristics:
      median age 39.0 years (interquartile range 26 to 52 years), female patients
      50.8%, motor vehicle crash 62.5%, fall 19.9%, admitted to the hospital 10.8%,
      clinically important cervical spine injury 0.6%, unimportant injury 0.3%, and
      internal fixation 0.3%. The paramedics classified patients for 12 important
      injuries with sensitivity 100% (95% confidence interval [CI] 74% to 100%) and
      specificity 37.7% (95% CI 36% to 40%). The kappa value for paramedic
      interpretation of the Canadian C-Spine Rule (n=155) was 0.93 (95% CI 0.87 to
      0.99). Paramedics conservatively misinterpreted the rule in 320 (16.4%) patients
      and were comfortable applying the rule in 1,594 (81.7%). Seven hundred thirty-one
      (37.7%) out-of-hospital immobilizations could have been avoided with the Canadian
      C-Spine Rule. CONCLUSION: This study found that paramedics can apply the Canadian
      C-Spine Rule reliably, without missing any important cervical spine injuries. The
      adoption of the Canadian C-Spine Rule by paramedics could significantly reduce
      the number of out-of-hospital cervical spine immobilizations.

PMID- 19394110
TI  - CARES: Cardiac Arrest Registry to Enhance Survival.
AB  - Despite 3 decades of scientific progress, rates of survival from out-of-hospital
      cardiac arrest remain low. The Cardiac Arrest Registry to Enhance Survival
      (CARES) was created to provide communities with a means to identify cases of out
      of-hospital cardiac arrest, measure how well emergency medical services (EMS)
      perform key elements of emergency cardiac care, and determine outcomes through
      hospital discharge. CARES collects data from 3 sources-911 dispatch, EMS, and
      receiving hospitals-and links them to form a single record. Once data entry is
      completed, individual identifiers are stripped from the record. The anonymity of
      CARES records allows participating agencies and institutions to compile cases
      without informed consent. CARES generates standard reports that can be used to
      characterize the local epidemiology of cardiac arrest and help managers determine
      how well EMS is delivering out-of-hospital cardiac arrest care. After pilot
      implementation in Atlanta, GA, and subsequent expansion to 7 surrounding
      counties, CARES was implemented in 22 US cities with a combined population of 14
      million people. Additional cities are interested in joining the registry. CARES
      currently contains more than 13,000 cases and is growing rapidly.

PMID- 19394112
TI  - Is the ordering of imaging for suspected venous thromboembolism consistent with D
      dimer result?
AB  - STUDY OBJECTIVE: We assessed whether the ordering of imaging studies in patients
      with suspected venous thromboembolism was consistent with the results of D-dimer
      testing. METHODS: We performed a retrospective chart review of consecutive cases
      in which a D-dimer assay was performed at an urban academic emergency department
      during a 13-month period. Measurements included D-dimer result and results of
      imaging for venous thromboembolism. The primary outcome measure was the
      percentage of patients in each D-dimer category (positive or negative result with
      a cutoff value of 500 ng fibrinogen equivalent units/dL) who underwent subsequent
      imaging within 48 hours. We also report the results of the imaging studies
      obtained. RESULTS: A total of 553 D-dimer tests were ordered, with 266 (48.1%)
      negative and 287 (51.9%) positive results. Of patients with a negative D-dimer
      result, 37 (14%; 95% confidence interval [CI] 10% to 19%) underwent at least 1
      imaging study. Of patients with a positive D-dimer result, 137 (48%; 95% CI 42%
      to 54%) did not undergo imaging. CONCLUSION: Evaluation for venous
      thromboembolism occasionally proceeded despite a negative D-dimer result, whereas
      frequently no further evaluation occurred despite a positive result. These
      findings suggest that actual clinical practice differs from what is recommended
      by published algorithms that guide evaluation of patients with suspected venous
      thromboembolism.

PMID- 19394113
TI  - Improved medical student satisfaction and test performance with a simulation
      based emergency medicine curriculum: a randomized controlled trial.
AB  - STUDY OBJECTIVE: We determine the effect of a simulation-based curriculum on
      fourth-year medical student test performance and satisfaction during an emergency
      medicine clerkship. METHODS: This was a randomized controlled study using a
      crossover design for curriculum format and an anonymous end-of-rotation
      satisfaction survey. Students were randomized into 2 groups. One group started
      the rotation with simulation and the other with group discussion. Midrotation,
      they each crossed over to the opposite format. All students subsequently
      completed the same multiple choice examination. We assessed paired samples of the
      number of questions missed for material taught in each format. Students rated
      satisfaction with a 5-point Likert scale framed as attitude toward simulation
      compared with group discussion. Scores ranged from 5, signifying strong agreement
      with a statement, to 1, signifying strong disagreement. RESULTS: Ninety students
      (99%) completed the multiple choice test. Significantly fewer questions were
      missed for material presented in simulation format compared with group
      discussion, with a mean difference per student of 0.7 (95% confidence interval
      [CI] 0.3 to 1.0; P=.006). This corresponds to mean scores of 89.8% for simulation
      and 86.4% for group discussion. Eighty-eight (97%) students completed the
      satisfaction survey. Students rated simulation as more stressful (mean 4.1; 95%
      CI 3.9 to 4.3), but also more enjoyable (mean 4.5; 95% CI 4.3 to 4.6), more
      stimulating (mean 4.7; 95% CI 4.5 to 4.8), and closer to the actual clinical
      setting (mean 4.6; 95% CI 4.4 to 4.7) compared with group discussion. CONCLUSION:
      A simulation-based curriculum yielded measurable benefits. Students demonstrated
      a small improvement in learning and were more satisfied with the simulation-based
      curriculum compared with group discussion.

PMID- 19394114
TI  - Transcription factor PITX3 gene in Parkinson's disease.
AB  - PITX3 is a transcription factor important for the differentiation and survival of
      midbrain dopaminergic neurons during the development. Recent reports suggest that
      single nucleotide polymorphisms (SNP) in the gene may be associated with
      Parkinson's disease (PD). To verify their findings and to determine the nature of
      the association in a subset of our PD patients we have analyzed two PITX3 SNPs
      (rs2281983 and rs4919621) in 265 PD patients and compared them with 210 age
      matched healthy controls. Our data show that the substitutions of C/T in SNP1 and
      A/T in SNP2 are significantly higher in PD, and this finding is even more robust
      in young onset and familial PD as compared with age-matched healthy controls. Our
      findings indicate that PITX3 may play a role in the pathogenesis of PD.

PMID- 19394115
TI  - 'When an old rat smells a cat': A decline in defense-related, but not accessory
      olfactory, Fos expression in aged rats.
AB  - Comparisons were made between young (3-6 months) and aged (20-30 months) Wistar
      rats on locomotor activity, emergence, social interaction and cat odor avoidance.
      Aged rats were less active and spent less time in the open field during the
      emergence test than younger rats. Older rats also showed fewer contacts with a
      novel conspecific in the social interaction test, although total duration of
      interaction did not differ. There were very few behavioral differences between
      male and female rats. Older rats were less reactive than younger rats in a test
      of cat odor avoidance. However, they expressed similar amounts of cat odor
      induced Fos in the posterior accessory olfactory bulb, a critical region for
      processing the predator odor stimulus. Older rats had reduced Fos expression in
      several defense-related brain regions that are normally activated by predator
      odors such as the medial amygdala and dorsal premammillary nucleus. These results
      indicate that aged rats are less reactive than younger rats to predator odors due
      to decreased responsiveness in defense-related but not necessarily olfactory
      circuits.

PMID- 19394116
TI  - Phenethyl pyridines with non-polar internal substituents as selective ligands for
      estrogen receptor beta.
AB  - To create estrogen receptor beta (ERbeta)-selective ligands with improved
      biological characteristics, we have extended our investigations of structurally
      simple bibenzyl-core ligands by preparing a series of compounds in which one
      phenol is replaced by a 3-hydroxypyridine ring. These phenethyl pyridines were
      obtained by picoline anion alkylation, and compounds with different patterns of
      alkyl substitution on the central two carbon units were prepared. Binding
      affinities for ERalpha and ERbeta were determined, and ligands with promising
      affinities and selectivities for ERbeta were further tested for their gene
      transcriptional activity. Several compounds had high affinity selectivity and
      good potency selectivity in transcription assays. This study advances our
      understanding of compounds having ER-subtype selectivity and will help to direct
      efforts in developing novel ER ligands.

PMID- 19394119
TI  - Using sequential extraction techniques to assess the partitioning of plutonium
      and neptunium-237 from multiple sources in sediments from the Ob River (Siberia).
AB  - Sequential extraction techniques have been developed to assess partitioning of
      anthropogenic radionuclides ((240)Pu, (239)Pu, and (237)Np), originating from a
      variety of sources, as identified by using bulk sediment isotopic composition.
      Sediments were leached sequentially with a series of six chemical treatments
      designed to approximate different environmental processes that may occur or to
      selectively extract trace metals contained in different solid phases of the
      sediments (i.e., exchangeable, reducible, carbonate, organic, acid leachable, and
      refractory). Results indicate the majority of Pu and Np is similarly distributed
      within many of the extracted fractions, with the largest percentage (66-97%) of
      both elements being observed in sediments treated with buffered citrate
      dithionite (CDB), which targets easily reduced constituents such as Mn and Fe
      hydrous oxides. While these results do indicate an association of Pu and Np with
      redox sensitive elements, the environmental implications are unclear given that
      the CDB treatment is more extreme than naturally occurring conditions. Minor
      amounts of Np partition differently from Pu in sediments. The NH(4)-acetate
      treatment, which is designed to liberate trace metals that are loosely adsorbed
      onto the surfaces of sedimentary materials such as hydrated iron oxides and humic
      substances, or present at exchangeable sites in clay minerals, mobilized
      approximately 12% of the total Np while Pu levels were below detection. The
      H(2)O(2) treatment, which is designed to liberate trace metals bound to organic
      matter, mobilized approximately 8 and approximately 1% of Np and Pu,
      respectively. These results indicate that a minor portion of the total Np may be
      affected by environmental conditions that have little or no effect on Pu. Between
      7 and 24% of the Pu was observed in treatments designed to liberate Pu and Np
      that are tightly bound to lithogenic phases or refractory silicates. The
      (240)Pu/(239)Pu observed in accessible and refractory fractions ranged between
      0.11 and 0.18. With the exception of one sample, the (240)Pu/(239)Pu isotope
      ratios measured in the refractory fractions are essentially identical having a
      mean ratio value of 0.123+/-0.001 (1sigma). The (240)Pu/(239)Pu ratios provide
      isotopic evidence that suggests a portion of non-fallout contamination has a
      refractory nature. The presence of similarly low (240)Pu/(239)Pu ratios in
      refractory fractions of sediments from the Ob and Irtysh Rivers suggests the
      existence of a source of refractory Pu which is consistent with refractory "hot
      particles" derived from surface tests at the Semipalitinsk test site.

PMID- 19394120
TI  - Changing health status and health expectancies among older adults in China:
      gender differences from 1992 to 2002.
AB  - Numerous studies document improvements in health status and health expectancies
      among older adults over time. However, most evidence is from developed nations
      and gender differences in health trends are often inconsistent. It remains
      unknown whether changes in health in developing countries resemble Western trends
      or whether patterns of health improvement are unique to the country's
      epidemiologic transition and gender norms. Using two nationally representative
      samples of non-institutionalized adults in China aged 65 years and older, this
      study investigates gender differences in the improvements in disability, chronic
      disease prevalence, and self-rated health from 1992 to 2002. Results from
      multivariate logistic regression models show that all three indicators of health
      improved over the 10-year period, with the largest improvement in self-rated
      health. With the exception of disability, the health of women improved more than
      men. Using Sullivan's decomposition methods, we also show that active life
      expectancy, disease-free life expectancy, and healthy life expectancy increased
      over this decade and were patterned differently according to gender. Overall, the
      findings demonstrate that China experienced broad health improvements during its
      early stages of the epidemiologic transition and that these changes were not
      uniform by gender. We discuss the public health implications of the findings in
      the context of China's rapidly aging population.

PMID- 19394121
TI  - A comparison of HIV stigma and discrimination in five international sites: the
      influence of care and treatment resources in high prevalence settings.
AB  - What accounts for differences in HIV stigma across different high prevalence
      settings? This study was designed to examine HIV stigma and discrimination in
      five high prevalence settings. Qualitative data were collected as part of the
      U.S. National Institute of Mental Health (NIMH) Project Accept, a multi-site
      community randomized trial of community-based HIV voluntary counseling and
      testing. In-depth interviews were conducted with 655 participants in five sites,
      four in Sub-Saharan Africa and one in Southeast Asia. Interviews were conducted
      in the local languages by trained research staff. Data were audiotaped,
      transcribed, translated, coded and computerized for thematic data analysis.
      Participants described the stigmatizing attitudes and behaviors perpetuated
      against people living with HIV/AIDS (PLWHA). The factors that contribute to HIV
      stigma and discrimination include fear of transmission, fear of suffering and
      death, and the burden of caring for PLWHA. The family, access to antiretrovirals
      and other resources, and self-protective behaviors of PLWHA protected against HIV
      stigma and discrimination. Variation in the availability of health and
      socioeconomic resources designed to mitigate the impact of HIV/AIDS helps explain
      differences in HIV stigma and discrimination across the settings. Increasing
      access to treatment and care resources may function to lower HIV stigma, however,
      providing services is not enough. We need effective strategies to reduce HIV
      stigma as treatment and care resources are scaled up in the settings that are
      most heavily impacted by the HIV epidemic.

PMID- 19394122
TI  - Drivers of tuberculosis epidemics: the role of risk factors and social
      determinants.
AB  - The main thrust of the World Health Organization's global tuberculosis (TB)
      control strategy is to ensure effective and equitable delivery of quality assured
      diagnosis and treatment of TB. Options for including preventive efforts have not
      yet been fully considered. This paper presents a narrative review of the
      historical and recent progress in TB control and the role of TB risk factors and
      social determinants. The review was conducted with a view to assess the prospects
      of effectively controlling TB under the current strategy, and the potential to
      increase epidemiological impact through additional preventive interventions. The
      review suggests that, while the current strategy is effective in curing patients
      and saving lives, the epidemiological impact has so far been less than predicted.
      In order to reach long-term epidemiological targets for global TB control,
      additional interventions to reduce peoples' vulnerability for TB may therefore be
      required. Risk factors that seem to be of importance at the population level
      include poor living and working conditions associated with high risk of TB
      transmission, and factors that impair the host's defence against TB infection and
      disease, such as HIV infection, malnutrition, smoking, diabetes, alcohol abuse,
      and indoor air pollution. Preventive interventions may target these factors
      directly or via their underlying social determinants. The identification of risk
      groups also helps to target strategies for early detection of people in need of
      TB treatment. More research is needed on the suitability, feasibility and cost
      effectiveness of these intervention options.

PMID- 19394123
TI  - Schizotypal personality traits and atypical lateralization in motor and language
      functions.
AB  - Atypical cerebral lateralization in motor and language functions in regard to
      schizotypal personality traits in healthy populations, as well as among
      schizophrenic patients, has attracted attention because these traits may
      represent a risk factor for schizophrenia. Although the relationship between
      handedness and schizotypal personality has been widely examined, few studies have
      adopted an experimental approach. This study consisted of three experiments
      focusing on motor and language functional lateralization in regard to schizotypal
      personality in the absence of mental illness: line-drawing, finger tapping, and a
      semantic go/no-go task. The results suggested that positive schizotypal
      personality might be related to functional non-lateralization in regard to at
      least some functions (e.g., spatial motor control and semantic processing in the
      present study). Subjects with high schizotypal personality traits performed
      equally with their right and left-hands in the line-drawing task and they reacted
      equally with their right and left-hands in a semantic go/no-go task involving
      semantic auditory stimuli presented in both ears. However, those low in
      schizotypal personality traits showed typical lateralization in response to these
      tasks. We discuss the implications of these findings for schizotypal atypical
      lateralization.

PMID- 19394125
TI  - Suggested modification to symptomatic tachycardia management algorithm (advanced
      life support).

PMID- 19394124
TI  - Polyphenolic beverages reduce initial bacterial adherence to enamel in situ.
AB  - OBJECTIVES: Polyphenols are antibacterial and anti-oxidative natural agents. The
      present in situ study aimed to investigate the effect of different polyphenolic
      beverages on initial bacterial adherence to enamel in the oral cavity. METHODS:
      Initial biofilm formation was performed on bovine enamel specimens mounted
      buccally on individual upper jaw splints and carried by six subjects. After 1 min
      of pellicle formation, oral rinses with black tea, green tea, grape juice, Cistus
      tea or red wine were performed for 10 min. Afterwards the slabs were carried for
      another 19 or 109 min, respectively. Samples exposed to the oral fluids for 30
      and 120 min served as controls. Following intraoral exposure, the slabs were
      rinsed with saline solution. The amount of adherent bacteria was determined with
      DAPI-staining (4',6-diamidino-2-phenylindole) and with fluorescence-in situ
      hybridization (FISH) of eubacteria and streptococci. RESULTS: Rinses with all
      beverages reduced the amount of detectable bacteria. Lowest number of adherent
      bacteria was found following rinses with red wine, Cistus tea and black tea as
      measured with DAPI (up to 66% reduction of adherent bacteria vs. controls). Also
      FISH revealed significant impact of most tested beverages. CONCLUSIONS: Rinses
      with certain polyphenolic beverages as well as consumption of these foodstuffs
      may contribute to prevention of biofilm induced diseases in the oral cavity.

PMID- 19394126
TI  - A multi-professional full-scale simulation course in the recognition and
      management of deteriorating hospital patients.
AB  - INTRODUCTION: Recognition and management of deteriorating patients is often
      suboptimal, resulting in adverse events that may be avoided if a unified
      understanding of the signs and needs of deteriorating patients is secured through
      the education of staff. This paper describes the planning and evaluation of a
      multi-professional, full-scale simulation-based course for hospital
      professionals. METHODS: A systematic approach to course development was used and
      the programme was introduced on four general wards in a university hospital.
      Experts from the wards were trained as educators and participated in the course
      development. A needs assessment consisting of an observational study,
      questionnaires and interviews resulted in the creation of learning objectives to
      provide the road map for content and teaching methods. A 1-day multi-professional
      ward-specific educational programme with full-scale simulations, mini-lectures,
      case discussions and practical training was planned. Course material, a manual
      for educators and questionnaires for evaluation of the course were developed.
      RESULTS: A 1-day full-scale simulation-based educational programme was developed
      and 50% of the medical staff and 70% of the nursing staff on four wards were
      trained in a 5-month period. The course was highly rated in terms of content and
      teaching methods. DISCUSSION: The systematic approach for developing the course
      resulted in a relevant, highly rated course, deeply rooted in the wards, implying
      the opportunity to facilitate local improvements and adjust the content to local
      needs. CONCLUSION: The use of a systematic approach was successful in the
      development of this multi-professional full-scale simulation-based educational
      programme, which has proven to be easily applicable and usable.

PMID- 19394127
TI  - Deep venous thrombosis in gynecological oncology: incidence and clinical symptoms
      study.
AB  - OBJECTIVE: Cancer patients have increased risks of leg deep venous thrombosis
      (DVT). We studied the incidence, risk factors and most predictive symptoms of leg
      DVT in gynecologic oncology patients. STUDY DESIGNS: Gynecologic oncology
      patients with any leg DVT symptoms were recruited and screened using Doppler
      sonogram. All hospitalized surgery and non-ambulating patients received thigh
      high sequential compression devices (SCDs) without heparin as a prophylactic
      method against thrombosis. Statistical analysis was done using chi-square or
      Fisher's exact tests. RESULTS: Out of 1974 patients, 134 complained of lower limb
      symptoms. Doppler studies found 38 patients with leg DVT. Incidence of leg DVT
      was 36/853 (4.2%) in patients with cancer and 2/1121 (0.2%) in patients without
      cancer (odds ratio 2.8 with a diagnosis of cancer). Leg edema, erythema, fever,
      and warm leg were significant symptoms in diagnosing leg DVT (p<0.01). The cost
      of finding a leg DVT was $747.54. CONCLUSIONS: Clinical exam is less accurate
      than Doppler sonogram in diagnosing leg DVT. The incidence of leg DVT using SCD
      seems to be comparable with other studies. Finally, the cost of identifying leg
      DVT seems reasonable.

PMID- 19394128
TI  - Pre-eclampsia in the second pregnancy: does previous outcome matter?
AB  - OBJECTIVE: To assess the effect of initial pregnancy outcome and gestational age
      on the risk of pre-eclampsia in the second pregnancy. STUDY DESIGN: We conducted
      an observational study using routinely collected data from the Aberdeen Maternity
      and Neonatal Databank between 1986 and 2006. Cases were women who developed pre
      eclampsia in their second pregnancy and controls were normotensive in their
      second pregnancy. Crude and adjusted odds ratios were produced for each of the
      risk factors using logistic regression. RESULTS: Inter-pregnancy intervals of 6
      years or more were associated with increased incidence of pre-eclampsia (19.4%
      vs. 14.7%). A change of partner had a protective effect while an increase in BMI
      increased the risk of pre-eclampsia. A history of pre-eclampsia was associated
      with 5 times higher risk {adjusted O.R. 5.12 (95% C.I. 4.42-6.48)} of pre
      eclampsia in the second pregnancy. Compared to a term delivery, a previous second
      trimester pregnancy loss was associated with a 4 times higher risk {adjusted O.R.
      4.22 (95% C.I. 2.54-7.03)} of pre-eclampsia in the next pregnancy. Previous very
      preterm and preterm births were associated with adjusted odds ratios of 2.32 (95%
      C.I. 1.62-3.32) and 1.62 (95% C.I. 1.46-1.72) respectively. The risk of pre
      eclampsia was no higher in women with a previous history of fetal death after 20
      weeks than those with a previous live birth, after adjusting for pre-eclampsia in
      the first pregnancy. CONCLUSION: Only initial deliveries beyond 37 weeks,
      irrespective of outcome, were protective against pre-eclampsia in the second
      pregnancy.

PMID- 19394130
TI  - Editorial comment on: Impact of percutaneous suprapubic tube drainage on patient
      discomfort after radical prostatectomy.

PMID- 19394129
TI  - A two-step strategy for neuronal differentiation in vitro of human dental
      follicle cells.
AB  - Human dental follicle cells (DFCs) derived from wisdom teeth are precursor cells
      for cementoblasts. In this study, we recognized that naive DFCs express
      constitutively the early neural cell marker beta-III-tubulin. Interestingly, DFCs
      formed beta-III-tubulin-positive neurosphere-like cell clusters (NLCCs) on low
      attachment cell culture dishes in serum-replacement medium (SRM). For a detailed
      examination of the neural differentiation potential, DFCs were cultivated in
      different compositions of SRM containing supplements such as N2, B27, G5 and the
      neural stem cell supplement. Moreover, these cell culture media were combined
      with different cell culture substrates such as gelatin, laminin, poly-L-ornithine
      or poly-L-lysine. After cultivation in SRM, DFCs differentiated into cells with
      small cell bodies and long cellular extrusions. The expression of nestin, beta
      III-tubulin, neuron-specific enolase (NSE) and neurofilament was up-regulated in
      SRM supplemented with G5, a cell culture supplement for glial cells, and the
      neural stem cell supplement. DFCs formed NLCCs and demonstrated an increased gene
      expression of neural cell markers beta-III-tubulin, NSE, nestin and for small
      neuron markers such as neuropeptides galanin (GAL) and tachykinin (TAC1) after
      cultivation on poly-L-lysine. For a further neural differentiation NLCC-derived
      cells were sub-cultivated on laminin and poly-L-ornithine cell culture substrate.
      After 2 weeks of differentiation, DFCs exposed neural-like cell morphology with
      small neurite-like cell extrusions. These cells differentially express
      neurofilament and NSE, but only low levels of beta-III-tubulin and nestin. In
      conclusion, we demonstrated the differentiation of human DFCs into neuron-like
      cells after a two-step strategy for neuronal differentiation.

PMID- 19394131
TI  - Impact of percutaneous suprapubic tube drainage on patient discomfort after
      radical prostatectomy.
AB  - BACKGROUND: Patients undergoing radical prostatectomy (RP) traditionally require
      urethral catheterization for adequate bladder drainage in the postoperative
      period. However, many patients have significant discomfort from the urethral
      catheter. OBJECTIVE: To describe a technique of percutaneous suprapubic tube
      (PST) bladder drainage after robotic-assisted laparoscopic radical prostatectomy
      (RALP) and to evaluate patient discomfort, complications, continence, and
      stricture rate after this procedure. DESIGN, SETTING, AND PARTICIPANTS: Two
      hundred two patients undergoing RALP were drained with a 14F PST instead of a
      urethral catheter. The PST was placed robotically at the conclusion of the
      urethrovesical anastomosis and secured to the skin over a plastic button.
      Beginning on postoperative day 5, patients clamped the PST, urinated per urethra,
      and measured the postvoid residual (PVR) drained by PST. The PST was removed when
      residuals were <30 cm(3) per void. The control group consisted of 50 consecutive
      patients undergoing RALP with urethral catheter drainage. MEASUREMENTS: The
      primary end point was catheter-associated discomfort as measured with the Faces
      Pain Score-Revised (FPS-R). Secondary end points included use of
      anticholinergics, complications related to the PST, urinary continence, and
      urethral stricture. RESULTS AND LIMITATIONS: When compared with urethral catheter
      patients, PST patients had significantly decreased catheter-related discomfort on
      postoperative days 2 and 6 (p<0.001). Anticholinergic medication was required by
      one PST and four urethral catheter patients (p<0.001). Ten patients required
      urethral catheterization for PST dislodgement (n=5) or urinary retention (n=5).
      No patient has developed a urethral stricture at a mean follow-up of 7 mo.
      CONCLUSIONS: PST provides adequate urinary drainage following RALP with less
      patient discomfort and no increased risk of urethral stricture.

PMID- 19394132
TI  - Prostate cancer screening: the need for problem-solving that puts men's interests
      first.

PMID- 19394134
TI  - Editorial comment on: complete continence after botulinum neurotoxin type a
      injections for refractory idiopathic detrusor overactivity incontinence: patient
      reported outcome at 4 weeks.

PMID- 19394133
TI  - Complete continence after botulinum neurotoxin type A injections for refractory
      idiopathic detrusor overactivity incontinence: patient-reported outcome at 4
      weeks.
AB  - BACKGROUND: Objective improvement following intradetrusor injections of botulinum
      neurotoxin type A (BoNTA) is well documented. Although patient-related outcome
      measures are highly recommended for monitoring overactive bladder symptoms, no
      study before has dealt with the question of patient-reported complete continence
      after BoNTA treatment using validated questionnaires. OBJECTIVE: To investigate
      the change in patient-reported continence rate after intradetrusor injections of
      BoNTA for treatment of refractory idiopathic detrusor overactivity (IDO)
      incontinence. DESIGN, SETTING, AND PARTICIPANTS: Seventy-four patients (51 women,
      23 men) with refractory IDO incontinence treated for the first time with
      intradetrusor injections of 200 U BoNTA were evaluated in this nonrandomised,
      open-label, cohort study. MEASUREMENTS: Changes in patient-reported urinary
      frequency, urgency incontinence, and stress incontinence were assessed using the
      condition-specific validated short form of the Urogenital Distress Inventory (UDI
      6) before and 4 wk after BoNTA treatment. RESULTS AND LIMITATIONS: The patient
      reported outcome of complete continence (defined as a score of 0 in both the
      urgency and stress incontinence subscales of the UDI 6) was 51% (38 of 74) 4 wk
      after intradetrusor injections of BoNTA. In patients who were not completely
      continent, median urgency incontinence scores reduced significantly from 100 to 0
      (p<0.001), stress incontinence scores from 33 to 0 (p<0.001), and median urinary
      frequency scores from 100 to 33 (p<0.001), respectively. The inclusion of
      patients with mixed incontinence may have resulted in underestimation of the
      complete continence rate. CONCLUSIONS: An excellent response with >50% of
      patients reporting complete continence 4 wk after BoNTA treatment reveals the
      efficacy of this emerging treatment for patients with refractory IDO
      incontinence. Furthermore, in those in whom complete continence was not achieved,
      there was a notable and significant reduction in reported urgency incontinence,
      stress incontinence, and urinary frequency.

PMID- 19394135
TI  - Editorial comment on: complete continence after botulinum neurotoxin type a
      injections for refractory idiopathic detrusor overactivity incontinence: patient
      reported outcome at 4 weeks.

PMID- 19394136
TI  - Delayed coma in head injury: consider cerebral fat embolism.
AB  - OBJECTIVE: To describe a case of a young man with delayed coma after mild head
      injury, suggestive of cerebral fat embolism (CFE). To underline the value of MR
      imaging in the differential diagnosis of secondary deterioration in mild head
      injury. CASE REPORT: A 21-year-old man admitted with mild head injury after a
      fall with facial fractures and long bone fractures. He was admitted to the
      intensive care unit and was mechanically ventilated. Weaning was not possible
      because of desaturations and pulmonary congestion. Low platelet count and anaemia
      developed. On several time points during his admission cerebral imaging data were
      obtained. Non-contrast CT on admission was normal while follow-up MRI showed
      extensive white matter abnormalities. These imaging abnormalities combined with
      the clinical presentation suggests cerebral fat embolism (CFE) as the most likely
      cause of secondary deterioration in our patient. CONCLUSIONS: In head injured
      patients with long bone fractures one should consider cerebral fat embolism. When
      the classical clinical syndrome is not present, MR imaging is warranted for
      diagnosis and to exclude other causes of secondary deterioration.

PMID- 19394137
TI  - Growth-inhibitory effects of a mineralized extract from the red marine algae,
      Lithothamnion calcareum, on Ca(2+)-sensitive and Ca(2+)-resistant human colon
      carcinoma cells.
AB  - Proliferation and differentiation were assessed in a series of human colon
      carcinoma cell lines in response to a mineral-rich extract derived from the red
      marine algae, Lithothamnion calcareum. The extract contains 12% Ca2+, 1% Mg2+,
      and detectable amounts of 72 trace elements, but essentially no organic material.
      The red algae extract was as effective as inorganic Ca2+ alone in suppressing
      growth and inducing differentiation of colon carcinoma cells that are responsive
      to a physiological level of extracellular Ca2+ (1.4mM). However, with cells that
      are resistant to Ca2+ alone, the extract was still able to reduce proliferation
      and stimulate differentiation.

PMID- 19394138
TI  - Critical role of TRPC6 channels in VEGF-mediated angiogenesis.
AB  - Intracellular Ca(2+) signaling plays critical roles in VEGF-mediated
      angiogenesis. Transient receptor potential canonical (TRPC) channel 6, a Ca(2+)
      permeable non-selective cation channel, can be activated by VEGF. Here, we report
      that TRPC6 is important for VEGF-mediated angiogenesis. Inhibition of TRPC6 in
      human umbilical vein endothelial cells (HUVECs) by pharmacological or genetic
      approaches arrested HUVECs at G2/M phase and suppressed VEGF-induced HUVEC
      proliferation and tube formation. Furthermore, inhibition of TRPCs abolished VEGF
      , but not FGF-induced angiogenesis in the chick embryo chorioallantoic membrane.
      These results suggest that TRPC6 plays an important role in VEGF-mediated
      angiogenesis.

PMID- 19394139
TI  - Spontaneous immortalization of oligodendroglial cells derived from an SV40 T
      antigen-positive human glioblastoma multiforme.
AB  - The polyoma group of viruses, including SV40, is known to be oncogenic in certain
      species. Here we report for the first time naturally occurring, immortalized
      tumor cells from a patient with glioblastoma multiforme (GBM); the cells were
      shown to be oligodendroglia; cells had developed remarkable chromosomal changes
      and were positive for SV40 T antigen. Therefore, we postulated that the main
      cause of immortalization of these cells was the expression of SV40 T antigen gene
      and protein. Since the cells are naturally generated, they will provide a useful
      model to study the function of oligodendroglial cells and the development of GBM.

PMID- 19394140
TI  - Lumican core protein inhibits melanoma cell migration via alterations of focal
      adhesion complexes.
AB  - Lumican is a small leucine-rich proteoglycan (SLRP) of the extracellular matrix
      (ECM) with anti-tumor activity. We recently demonstrated that lumican inhibits
      the migration of melanoma cells and identified beta1 integrin as mediator of this
      effect [M.F. D'Onofrio, S. Brezillon, T. Baranek, C. Perreau, P.J. Roughley, F.X.
      Maquart, Y. Wegrowski, Identification of beta1 integrin as mediator of melanoma
      cell adhesion to lumican, Biochem. Biophys. Res. Commun. 365 (2008) 266-272]. The
      aim of the present work was to study beta1 integrin, focal adhesion complexes,
      actin distribution and expression in the presence of lumican substratum in
      comparison to type I collagen or fibronectin substrata in A375 human melanoma
      cells. The protein distribution was investigated by immunocytochemistry and
      confocal microscopy. In parallel, their expression was evaluated by Western
      immunoblotting and Real-time Reverse Transcription-PCR analyses. The interaction
      of melanoma cells with the lumican substratum resulted in heterogeneous
      distribution of beta1 integrin on cell membrane after 24h of seeding.
      Concomitantly, a reorganization of actin stress fibers and a significant decrease
      in vinculin immunostaining at focal adhesion complexes were observed. No
      alteration of the expression was detected at protein and mRNA levels. However, a
      cytosolic accumulation of vinculin focal adhesion protein was observed on lumican
      substratum by confocal microscopy. Moreover, vinculin expression was
      significantly increased in cytosolic fractions in comparison to cells seeded on
      type I collagen or fibronectin substrata. Our results suggest that lumican
      induces an alteration of the link between actin filaments and beta1 integrin,
      characterized by a cytosolic accumulation of vinculin focal adhesion protein,
      which could lead to a destabilization of focal adhesion complexes. In addition,
      focal adhesion kinase phosphorylated at tyrosine-397 (pFAK) was significantly
      decreased. Therefore, the cytoskeleton remodeling and the decreased pFAK
      phosphorylation induced by lumican in melanoma cells might explain, at least in
      part, the anti-invasive effect of this SLRP.

PMID- 19394141
TI  - Studies on solvent extraction of copper and cyanide from waste cyanide solution.
AB  - The recovery of copper and cyanide from waste cyanide solution with the guanidine
      extractant (LIX 7950) and the modified amine extractant (LIX 7820) has been
      investigated. Copper can be effectively extracted from alkaline cyanide solutions
      by both extractants. The free cyanide remains in the aqueous phase due to the
      preferential extraction of Cu(CN)(3)(2-) over Cu(CN)(4)(3-) and CN(-) by the
      extractants. The selectivity of the metals with the extractants under different
      cyanide levels has been examined. High cyanide levels tend to depress extraction
      of copper and silver cyanides, but exhibit insignificant effect on extraction of
      gold, zinc, nickel and iron cyanides. A possible solution to the separation of
      copper cyanides and free cyanide in cyanide effluents has been suggested, by
      which copper can be concentrated into a small volume of solution and the barren
      cyanide solution recycled to the cyanidation process.

PMID- 19394142
TI  - Biosorption of Cu(II) ions from aqueous effluents by blackgram bran (BGB).
AB  - Biosorption of Cu(II) ions onto blackgram bran (BGB) waste biomass in a well
      stirred batch system was investigated and optimum conditions were determined. The
      maximum Cu(II) uptake capacity of BGB was 107.65 mg L(-1) at pH 5, biosorbent
      dose 0.025 g/100mL, biosorbent particle size <0.250 mm at an initial metal
      concentration of 50 mg L(-1) achieved after equilibrium time of 480 min. The
      equilibrium data fitted very well to Langmuir isotherm model as compared to the
      isothermal model of Freundlich. The pseudo 1st and 2nd order kinetic models were
      used to describe the kinetic data. The experimental data fitted well to 2nd order
      kinetic model. Due to its outstanding Cu(II) ions uptake capacity, BGB biomass
      proved to be an excellent material of bioorigin for accumulating Cu(II) ions from
      aqueous solutions.

PMID- 19394143
TI  - Effects of substrates on biofilm formation observed by atomic force microscopy.
AB  - Formation of biofilm is known to be strongly dependent on substrates including
      topography, materials, and chemical treatment. In this study, a variety of
      substrates are tested for understanding biofilm formation. Sheets of aluminum,
      steel, rubber, and polypropylene have been used to examine their effects on
      formation of Pseudomonas aeruginosa biofilm. In particular, the morphological
      variation, transition, and adhesiveness of biofilm were investigated through
      local measurement by atomic force microscopy (AFM). Mechanism of removing biofilm
      from adhering to substrate is also analyzed, thus the understanding of the
      mechanism can be potentially useful to prevent the biofilm formation. The results
      reveal that formation of biofilm can remain on rough surface regardless of
      substrates in hot water, which may easily induce extra-polymeric substances
      detachment from bacterial surface. By probing using AFM, local force-distance
      characterization of extra-cellular materials extracted from the bacteria can
      exhibit the progress of the biofilm formation and functional complexities.

PMID- 19394144
TI  - Molecular order affecting electron transport through ssDNA.
AB  - DNA is considered to be the ideal model for studies of electron transport in
      molecule/conductor systems due to its stability, easily controlled structure and
      the presumed electrical properties. Scanning tunnelling microscope (STM) studies
      of single-stranded DNA bound to Au (111) or Au nanodots with a thiol linker were
      carried out under ambient conditions. The results show that the electron transfer
      between the STM tip and the gold is governed by the serial resistance of the
      oligomer strands and a water film. Electron transfer properties also depend on
      the alignment of the DNA strands. Measurements show that well-ordered parallel
      arrangement of the molecules protruding from flat crystalline surfaces is
      favourable for electron transport compared with unordered arrangements of
      molecules on spherical nanodots. Nanodots are good candidates for effective
      charge production by absorption of light allowing chemical reactions to happen at
      the dots, which can be used for storing the light energy. Understanding electron
      transport through molecular structures is of crucial importance for the
      development of such novel photovoltaic devices.

PMID- 19394145
TI  - Infectivity of gastric and intestinal Cryptosporidium species in immunocompetent
      Mongolian gerbils (Meriones unguiculatus).
AB  - We exposed juvenile (7-day old) and adult (8-week old) Mongolian gerbils
      (Meriones unguiculatus) to Cryptosporidium andersoni or C. muris, which infect
      the stomach, or to C. parvum, which infects the intestine. Both age groups could
      be successfully infected with each species in primary mono-infection with
      juvenile animals demonstrating higher peak oocysts per gram of feces and longer
      patent periods than adults. Concurrent exposure to mixed gastric and intestinal
      cryptosporidia resulted in successful infection with both species. The time
      course and infection intensities in the mixed infections were similar to those of
      primary mono-infection and for a given species. Similarly, sequential mixed
      infection of C. andersoni positive gerbils with C. muris 25 days after exposure
      to C. andersoni resulted in simultaneous infection with both gastric species. In
      contrast, following primary infection and clearance, animals re-exposed to the
      same Cryptosporidium species, failed to excrete oocysts in their feces and
      histological examination revealed no developmental stages in the stomach or
      intestine. In cross-infections, where the secondary exposure was with a different
      Cryptosporidium species than the initial cleared infection, successful infection
      was possible with a gastric species following C. parvum, or with C. parvum
      following a gastric species, but primary infection with one gastric species
      precluded secondary infection with the other gastric species. These results
      indicate cross-immunity between gastric Cryptosporidium species but not between
      intestinal and gastric species. Furthermore, our study demonstrates that
      Mongolian gerbils are susceptible to infection with many Cryptosporidium species
      and are a useful laboratory model for studies of mixed cryptosporidiosis.

PMID- 19394146
TI  - Preliminary studies on developing a nested PCR assay for molecular diagnosis and
      identification of nematode (Heterakis isolonche) and trematode (Glaphyrostomum
      sp.) in Okinawa rail (Gallirallus okinawae).
AB  - To investigate and detect internal parasites in Okinawa rail (Gallirallus
      okinawae), a novel nested polymerase chain reaction with high level of
      sensitivity and specificity was developed. Specific PCR primers that target
      partial DNA sequences of mitochondrial Cytochrome C oxidase subunit 1 (cox1) gene
      were designed to differentiate between nematode (Heterakis isolonche) and
      trematode (Glaphyrostomum sp.) found in the intestine of Okinawa rail. Nested PCR
      assay was established based on primers design and applied to seven fecal samples
      from road killed birds containing nematode and/or trematode eggs. The results
      indicated this new nested PCR protocol was available for the identification of
      parasites and of value to clinical application.

PMID- 19394147
TI  - Impact of rotational grazing on management of gastrointestinal nematodes in
      weaned lambs.
AB  - Gastrointestinal nematode (GIN) control for 'natural' or organic lamb production
      is needed, especially where Haemonchus contortus is prevalent. The objective was
      to determine the impact of rotational grazing on GIN infection of weaned lambs.
      In year 1, naturally infected Katahdin lambs (120 days of age) were randomly
      assigned to graze (1) continuous bermudagrass (CB; n=14), (2) rotational
      bermudagrass moved every 3.5 days and returned to original plot 35 days later for
      three rotations (RB; n=14), or (3) rotational bermudagrass rotated when forage
      height fell below 10 cm (RBH; n=7) where first day of grazing=Day 0. In late
      summer, all lambs were supplemented with 500 g corn/SBM because of poor
      condition. The following year, similar animals were used and included the CB
      (n=18) and the RB (n=36) groups only. In both years, fecal egg counts (FECs) and
      blood packed cell volume (PCV) were determined every 7-14 days and body weight
      every 28 days. Individuals were dewormed with 0.5 g copper oxide wire particles
      (COWP) when FAMACHA score increased to 3 or more. Between 0 and 3 deworming
      treatments per lamb were necessary and there tended to be fewer RB than CB lambs
      dewormed by Day 84 for both years combined (P<0.001). Worm free tracer lambs were
      introduced to CB (n=6) and RB (n=8) plots following the last rotation during the
      first year to determine worm burdens after 20 days of grazing. Abomasal worm
      burden tended to be greater in RB than CB or RBH tracer lambs (P<0.10), but
      intestinal worm numbers were similar. Differences may be due to differences in
      grazing patterns among groups. Body weight gains were similar between CB and RB
      groups. Economic value between the CB and RB lambs was similar based on number of
      lambs that could have been marketed as organic. For both years, lambs relied
      exclusively on COWP for GIN control with the exception of one lamb. In summary,
      while there was a reduced incidence of deworming in the RB compared with the CB
      group of lambs, estimated economic value of these systems was similar.

PMID- 19394149
TI  - Benign prostatic hyperplasia: the hypogonadal-obesity-prostate connection.
AB  - Prostatic enlargement occurs over the course of a lifetime and is associated with
      many risk factors. Recent observations demonstrate that valvular damage,
      occurring in the internal spermatic veins results in increased hydrostatic
      pressures that lead to venous backflow. Two consequences of venous backflow are
      the prolonged exposure to hydrostatic pressure and high testosterone levels that
      effect the prostate directly. Furthermore, aging and obesity related states have
      long been associated with BPH and diminished testosterone concentrations, which
      by itself, predisposes and allows for the preferential deposition of
      abdominal/visceral fat. The increasing abdominal obesity leads to elevated intra
      abdominal pressure, which over time, causes increased venous pressure.
      Chronically elevated intra-abdominal venous pressure eventually causes
      progressive failure of the one way valves in the internal spermatic veins and
      venous insufficiency that leads to prostate damage. All of these factors promote
      conditions that cause chronic progressive prostatic disease and eventually BPH.

PMID- 19394148
TI  - Characteristics associated with smoking in a Hispanic sample.
AB  - Although general smoking prevalence has declined, similar declines have not been
      observed in some underserved populations. For example, groups such as ethnic
      minorities, individuals with psychiatric diagnoses, those with a history of
      substance use, and weight concerned smokers have not shown comparable reductions.
      The goal of this study is to create a profile of Hispanic smokers in the El
      Paso/Juarez area and identify predictors of smoking. In this cross-sectional
      study, these variables were assessed in 160 English-speaking Hispanic volunteers.
      Participants completed measures of tobacco use, nicotine dependence, weekly
      alcohol consumption, acculturation, depressive symptomatology, weight concern,
      and drug use. Expired carbon monoxide and body composition were also assessed.
      Participants were light smokers with low levels of nicotine dependence and
      expired carbon monoxide, a significant number of past quit attempts, and limited
      use of cessation aids. Significant characteristics associated with smoking
      included male gender, use of mental health services, increasing number of drinks
      per week, and lifetime use of illicit drugs. These findings suggest substance use
      and psychiatric comorbidity are associated with smoking in this population and
      may be barriers to quitting. These factors should be considered in developing
      culturally-sensitive tobacco cessation interventions for Hispanic smokers,
      particularly those residing on the U.S./Mexico border.

PMID- 19394150
TI  - In restless legs syndrome, the neural substrates of the sensorimotor symptoms are
      also normally involved in upright standing posture and biped walking.
AB  - Restless legs syndrome (RLS) exhibits sensorimotor symptoms. In familial cases, a
      gene at chromosomal location 9p-24-22 is linked to RLS and the expressed mutation
      is Dopamine Receptor Specific Individual Sensitivity (DRSIS). The symptoms are
      triggered during changes in alertness, generally at sleep hours, resulting from
      insufficient dopamine transmission. The conscious experience of sensory
      abnormalities are described as 'an urge to move the limbs with or without
      paresthesias' leading to motor signs such as periodic limb movements and motor
      restlessness which exhibit temporary loss of extensor motor system dominance over
      the flexor motor system of the upright posture. The relationship of the expressed
      mutation to EEG alpha activity makes RLS a sleep disorder as well as a cognitive
      dysfunction. The recurrent character of sensorimotor symptoms impede the
      patient's ability to sleep, wake and force to move leading to insomnia. In Uner
      Tan Syndrome, the nonsense mutation in the same gene leads to underdevelopment of
      the neural substrates of upright posture. The defects include dopamine receptor
      deficiency (DRD) leading to severe cognitive dysfunctions and motor disorders
      complete loss of extensor motor system dominance over the flexor motor system
      quadrupedality, primitive speech, cerebellar symptoms, and strabismus.
      Comparisons between the neural substrates of sensorimotor symptoms seen in RLS
      and MRI findings for cases of Uner Tan Syndrome show cortico-cerebellar
      hypoplasias in the neural networks involved in upright posture. Both RLS and Uner
      Tan Syndrome seem to be due to different mutations in the dopamine receptor gene
      at 9p-24 locus, affecting the diencephalon dopaminergic system and the neural
      networks involved in upright posture.

PMID- 19394151
TI  - Toward a multi-dimensional formulation of the pathogenesis and pathophysiology of
      the Alzheimer dementia-like syndrome applicable to a variety of degenerative
      disorders and normal cognition.
AB  - Neurodegenerative disorders constitute a set of heterogeneous conditions lacking
      a satisfactory unifying conceptual scheme. This situation is widely perceived as
      hampering progress in understanding them adequately in order to develop effective
      treatment and prevention, but there is no unanimously or even generally agreed
      upon solution to this dilemma. Here, we propose that progress in resolving this
      conundrum requires addressing in an integrated fashion multiple dimensions and
      scales of organization and (normal and disordered) function that include, but
      transcend the conventional levels of space, time, Molecular Biology/Biochemistry
      and Systems Neuroscience, among others. This approach must include also a
      revision of the nosological concepts that currently attempt to force
      pathophysiological and etiological explanations within a single domain (nowadays
      predominantly the Molecular/Biochemical) that have virtually always failed to
      deliver on titillating expectations based on relatively simple "atomizing"
      schemes focusing on one domain/level, while ignoring virtually all others. This
      multi-dimensional integrated approach is illustrated for the Alzheimer dementia
      like syndrome taking advantage of the wealth of knowledge in several of the
      relevant domains, but is generally applicable to potentially the entire range of
      neurodegenerative disorders, and probably also to other aspects of normal and
      disordered cognition and behavior.

PMID- 19394152
TI  - Postconditioning in cardiopulmonary resuscitation: a better protocol for
      cardiopulmonary resuscitation.
AB  - Although current cardiopulmonary resuscitation (CPR) performance can increase the
      rates of restoration of spontaneous circulation (ROSC) and survival to hospital
      admission, the discharge rates of patients remain disappointing. The high
      mortality rate is attributed to post-cardiac arrest brain injury. The discovery
      of the postconditioning phenomenon opens a door to endogenous neuroprotection.
      The protection mechanisms of postconditioning include attenuating mitochondrial
      calcium overload and reducing oxidative stress, recruiting the reperfusion injury
      salvage kinase (RISK) pathway, and preventing from the mitochondrial permeability
      transition pore (mPTP) opening at the time of reperfusion. An advantage of
      postconditioning lies in the potentially clinical application in the unexpected
      ischemic situation. Prior laboratory researches indicate that postconditioning
      may lessen the reperfusion/ischemia-induced injury in unexpected coronary
      occlusion, acute myocardial infarction and stroke. Because cardiac arrest, stroke
      and acute myocardial infarction have a similar pathophysiological process, we
      hypothesize that postconditioning could be used in the clinical practice of CPR
      to treat patients with post-cardiac arrest brain injury. We propose a novel
      protocol of "Postconditioning cardiocerebral resuscitation (Post-CCR)". The Post
      CCR includes applying three cycles of 18s chest compression and 10s interruption
      for ventilation first, and then executing chest compression only CPR until the
      patients return spontaneous circulation. Post-CCR can not only provide vital
      blood flow to the heart and brain but also activate endogenous protective
      mechanism to lessen post-cardiac arrest brain injury. We consider that it would
      become a feasible, safe and efficient cerebralprotective intervention in the
      prevention and alleviation of post-cardiac arrest brain injury, which would also
      improve the outcome after cardiac arrest.

PMID- 19394153
TI  - Imaging after GliaSite brachytherapy: prognostic MRI indicators of disease
      control and recurrence.
AB  - PURPOSE: In this study, we analyzed the magnetic resonance imaging (MRI) changes
      in patients after GliaSite treatment and characterized the prognostic MRI
      indicators in these patients. METHODS AND MATERIALS: A total of 25 patients with
      recurrent glioblastoma multiforme were treated with the GliaSite Radiation
      Therapy System. Patients at the Johns Hopkins Hospital with recurrent
      glioblastoma multiforme underwent surgical resection followed by GliaSite balloon
      implantation. Available MRI scans for 20 patients were obtained throughout the
      post-GliaSite treatment course. These were reviewed and analyzed for prognostic
      significance. RESULTS: After GliaSite treatment, all patients developed some
      degree of T(1)-weighted contrast and T(2)-weighted hyperintensity around the
      resection cavity. The development of enhancement on T(1)-weighted contrast
      enhanced imaging and the size of these lesions, in the absence of increasing T(2)
      weighted hyperintensity, before clinical progression was not associated with
      decreased survival. Patients with T(1)-weighted enhancement >1 cm had a median
      survival of 13.6 months and those with T(1)-weighted lesions <or=1 cm had a
      median survival of 8.5 months (p = .014). In contrast, the development of larger
      areas of T(2)-weighted hyperintensity surrounding the resection cavity was
      significantly associated with poorer survival (p = .027). CONCLUSION: After
      GliaSite treatment, characteristic T(1)- and T(2)-weighted changes are seen on
      MRI. Greater T(1)-weighted changes in the absence of increasing edema appears not
      to indicate disease progression; however, greater T(2)-weighted changes were
      associated with decreased survival. These findings suggest that T(1)-weighted
      enhancement in the absence of concomitant edema after GliaSite treatment might
      represent pseudoprogression. Conversely, increasing T(2)-weighted hyperintensity
      might reflect infiltrative disease progression. These results provide a framework
      for the analysis of disease control in future prospective studies of GliaSite
      treatment.

PMID- 19394154
TI  - Defining the clinical target volume for bladder cancer radiotherapy treatment
      planning.
AB  - PURPOSE: There are currently no data for the expansion margin required to define
      the clinical target volume (CTV) around bladder tumors. This information is
      particularly relevant when perivesical soft tissue changes are seen on the
      planning scan. While this appearance may reflect extravesical extension (EVE), it
      may also be an artifact of previous transurethral resection (TUR). METHODS AND
      MATERIALS: Eighty patients with muscle-invasive bladder cancer who had undergone
      radical cystectomy were studied. All patients underwent preoperative TUR and
      staging computed tomography (CT) scans. The presence and extent of tumor growth
      beyond the outer bladder wall was measured radiologically and
      histopathologically. RESULTS: Forty one (51%) patients had histologically
      confirmed tumor extension into perivesical fat. The median and mean extensions
      beyond the outer bladder wall were 1.7 and 3.1 mm, respectively. Thirty five
      (44%) patients had EVE, as seen on CT scans. The sensitivity and specificity of
      CT scans for EVE were 56% and 79%, respectively. False-positive results were
      infrequent and not affected by either the timing or the amount of tissue resected
      at TUR. CT scans consistently tended to overestimate the extent of EVE. Tumor
      size and the presence of either lymphovascular invasion or squamoid
      differentiation predict a greater extent of EVE. CONCLUSIONS: In patients with
      radiological evidence of extravesical disease, the CTV should comprise the outer
      bladder wall plus a 10-mm margin. In patients with no evidence of extravesical
      disease on CT scans, the CTV should be restricted to the outer bladder wall plus
      a 6-mm margin. These recommendations would encompass microscopic disease
      extension in 90% of cases.

PMID- 19394156
TI  - Outcomes of adjuvant chemoradiation after pancreaticoduodenectomy with
      mesenterico-portal vein resection for adenocarcinoma of the pancreas.
AB  - PURPOSE: Surgery followed by chemotherapy and radiation (CRT) offers patients
      with pancreatic adenocarcinoma a chance for extended survival. In some patients,
      however, resection is difficult because of vascular involvement by the carcinoma,
      necessitating resection and grafting of the mesenterico-portal vessels. The
      purpose of this study was to compare outcomes between pancreaticoduodenectomy
      (PD) with and without mesenterico-portal vein resection (VR) in patients
      receiving adjuvant CRT for pancreatic adenocarcinoma. METHODS AND MATERIALS:
      Between 1993 and 2005, 160 patients underwent PD with 5-FU-based adjuvant CRT
      followed by maintenance chemotherapy at the Johns Hopkins Hospital; 20 (12.5%) of
      the 160 underwent VR. Clinical outcomes, including median survival, overall
      survival, and complication rates were assessed for both groups. RESULTS: Patients
      who underwent VR had significantly longer operative times (p = 0.009), greater
      intraoperative blood loss (p = 0.01), and longer postoperative lengths of stay (p
      = 0.03). However, postoperative morbidity, median survival, and overall survival
      rates were similar between the two groups. Most patients (70%) from both groups
      were able to complete CRT, and a subgroup analysis demonstrated no appreciable
      differences in terms of complications. None of the VR patients who received
      adjuvant CRT developed veno-oclusive disease or graft failure/leakage.
      CONCLUSION: In a cohort of patients treated with adjuvant 5-FU-based CRT at the
      Johns Hopkins Hospital, having a VR at the time of PD resulted in similar
      complication rates and survival. These data support the feasibility and safety of
      adjuvant CRT in patients undergoing VR at the time of PD.

PMID- 19394155
TI  - Organ preservation with concurrent chemoradiation for advanced laryngeal cancer:
      are we succeeding?
AB  - PURPOSE: To determine the rates of organ preservation and function in patients
      with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent
      chemoradiotherapy (CRT). METHODS AND MATERIALS: Between April 1999 and September
      2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas
      (33%) underwent conventional radiotherapy and concurrent platinum-based
      chemotherapy with curative intent. Sixty-two patients were male (75.6%). The
      median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%)
      were in Stage IV. The median radiation dose was 70 Gy. The median potential
      follow-up was 3.9 years. RESULTS: Overall survival and disease-free survival were
      respectively 63% and 73% at 3 years. Complete response rate from CRT was 75%.
      Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6
      (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent
      Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring
      multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a
      permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without
      pathologic evidence of disease. At last follow-up, 5 (6%) patients were still
      dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete
      response, with a functional larynx and no other major complications. CONCLUSIONS:
      In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has
      provided good overall survival and locoregional control in the majority of
      patients, but a significant proportion did not benefit from this approach because
      of either locoregional failure or late complications. Better organ preservation
      approaches are necessary to improve locoregional control and to reduce long-term
      toxicities.

PMID- 19394157
TI  - Treatment planning to improve delivery accuracy and patient throughput in helical
      tomotherapy.
AB  - PURPOSE: To investigate delivery quality assurance (DQA) discrepancies observed
      for a subset of helical tomotherapy patients. METHODS AND MATERIALS: Six
      tomotherapy patient plans were selected for analysis. Three had passing DQA ion
      chamber (IC) measurements, whereas 3 had measurements deviating from the expected
      dose by more than 3.0%. All plans used similar parameters, including: 2.5 cm
      field-width, 15-s gantry period, and pitch values ranging from 0.143 to 0.215.
      Preliminary analysis suggested discrepancies were associated with plans having
      predominantly small leaf open times (LOTs). To test this, patients with failing
      DQA measurements were replanned using an increased pitch of 0.287. New DQA plans
      were generated and IC measurements performed. Exit fluence data were also
      collected during DQA delivery for dose reconstruction purposes. RESULTS: Sinogram
      analysis showed increases in mean LOTs ranging from 29.8% to 83.1% for the
      increased pitch replans. IC measurements for these plans showed a reduction in
      dose discrepancies, bringing all measurements within +/-3.0%. The replans were
      also more efficient to deliver, resulting in reduced treatment times. Dose
      reconstruction results were in excellent agreement with IC measurements,
      illustrating the impact of leaf-timing inaccuracies on plans having predominantly
      small LOTs. CONCLUSIONS: The impact of leaf-timing inaccuracies on plans with
      small mean LOTs can be considerable. These inaccuracies result from deviations in
      multileaf collimator latency from the linear approximation used by the treatment
      planning system and can be important for plans having a 15-s gantry period. The
      ability to reduce this effect while improving delivery efficiency by increasing
      the pitch is demonstrated.

PMID- 19394160
TI  - Accuracy of ultrasound-based image guidance for daily positioning of the upper
      abdomen: an online comparison with cone beam CT.
AB  - PURPOSE: Image-guided intensity-modulated radiotherapy can improve protection of
      organs at risk when large abdominal target volumes are irradiated. We estimated
      the daily positioning accuracy of ultrasound-based image guidance for abdominal
      target volumes by a direct comparison of daily imaging obtained with cone beam
      computed tomography (CBCT). METHODS AND MATERIALS: Daily positioning (n = 83
      positionings) of 15 patients was completed by using ultrasound guidance after an
      initial CBCT was obtained. Residual error after ultrasound was estimated by
      comparison with a second CBCT. Ultrasound image quality was visually rated using
      a scale of 1 to 4. RESULTS: Of 15 patients, 7 patients had good sonographic
      imaging quality, 5 patients had satisfactory sonographic quality, and 3 patients
      were excluded because of unsatisfactory sonographic quality. When image quality
      was good, residual errors after ultrasound were -0.1 +/- 3.11 mm in the x
      direction (left-right; group systematic error M = -0.09 mm; standard deviation
      [SD] of systematic error, Sigma = 1.37 mm; SD of the random error, sigma = 2.99
      mm), 0.93 +/- 4.31 mm in the y direction (superior-inferior, M = 1.12 mm; Sigma =
      2.96 mm; sigma = 3.39 mm), and 0.71 +/- 3.15 mm in the z direction
      (anteroposterior; M = 1.01 mm; Sigma = 2.46 mm; sigma = 2.24 mm). For patients
      with satisfactory image quality, residual error after ultrasound was -0.6 +/-
      5.26 mm in the x (M = 0.07 mm; Sigma = 5.67 mm; sigma = 4.86 mm), 1.76 +/- 4.92
      mm in the y (M = 3.54 mm; Sigma = 4.1 mm; sigma = 5.29 mm), and 1.19 +/- 4.75 mm
      in the z (M = 0.82 mm; Sigma = 2.86 mm; sigma = 3.05 mm) directions. CONCLUSIONS:
      In patients from whom good sonographic image quality could be obtained,
      ultrasound improved daily positioning accuracy. In the case of satisfactory image
      quality, ultrasound guidance improved accuracy compared to that of skin marks
      only minimally. If sonographic image quality was unsatisfactory, daily CBCT
      scanning improved treatment accuracy distinctly over that of ultrasound. Use of
      daily ultrasound or CBCT imaging can help to reduce PTV margins and protect
      organs at risk compared to the use of skin mark-based positioning.

PMID- 19394158
TI  - Development of RTOG consensus guidelines for the definition of the clinical
      target volume for postoperative conformal radiation therapy for prostate cancer.
AB  - PURPOSE: To define a prostate fossa clinical target volume (PF-CTV) for Radiation
      Therapy Oncology Group (RTOG) trials using postoperative radiotherapy for
      prostate cancer. METHODS AND MATERIALS: An RTOG-sponsored meeting was held to
      define an appropriate PF-CTV after radical prostatectomy. Data were presented
      describing radiographic failure patterns after surgery. Target volumes used in
      previous trials were reviewed. Using contours independently submitted by 13
      radiation oncologists, a statistical imputation method derived a preliminary
      "consensus" PF-CTV. RESULTS: Starting from the model-derived CTV, consensus was
      reached for a CT image-based PF-CTV. The PF-CTV should extend superiorly from the
      level of the caudal vas deferens remnant to >8-12 mm inferior to vesicourethral
      anastomosis (VUA). Below the superior border of the pubic symphysis, the anterior
      border extends to the posterior aspect of the pubis and posteriorly to the
      rectum, where it may be concave at the level of the VUA. At this level, the
      lateral border extends to the levator ani. Above the pubic symphysis, the
      anterior border should encompass the posterior 1-2 cm of the bladder wall;
      posteriorly, it is bounded by the mesorectal fascia. At this level, the lateral
      border is the sacrorectogenitopubic fascia. Seminal vesicle remnants, if present,
      should be included in the CTV if there is pathologic evidence of their
      involvement. CONCLUSIONS: Consensus on postoperative PF-CTV for RT after
      prostatectomy was reached and is available as a CT image atlas on the RTOG
      website. This will allow uniformity in defining PF-CTV for clinical trials that
      include postprostatectomy RT.

PMID- 19394159
TI  - Integration of real-time internal electromagnetic position monitoring coupled
      with dynamic multileaf collimator tracking: an intensity-modulated radiation
      therapy feasibility study.
AB  - PURPOSE: Continuous tumor position measurement coupled with a tumor tracking
      system would result in a highly accurate radiation therapy system. Previous
      internal position monitoring systems have been limited by fluoroscopic radiation
      dose and low delivery efficiency. We aimed to incorporate a continuous,
      electromagnetic, three-dimensional position tracking system (Calypso 4D
      Localization System) with a dynamic multileaf collimator (DMLC)-based dose
      delivery system. METHODS AND MATERIALS: A research version of the Calypso System
      provided real-time position of three Beacon transponders. These real-time three
      dimensional positions were sent to research MLC controller with a motion-tracking
      algorithm that changed the planned leaf sequence. Electromagnetic transponders
      were embedded in a solid water film phantom that moved with patient lung
      trajectories while being irradiated with two different plans: a step-and-shoot
      intensity-modulated radiation therapy (S-IMRT) field and a dynamic IMRT (D-IMRT)
      field. Dosimetric results were recorded under three conditions: no intervention,
      DMLC tracking, and a spatial gating system. RESULTS: Dosimetric accuracy was
      comparable for gating and DMLC tracking. Failure rates for gating/DMLC tracking
      are as follows: +/-3 cGy 10.9/ 7.5% for S-IMRT, 3.3/7.2% for D-IMRT; gamma
      (3mm/3%) 0.2/1.2% for S-IMRT, 0.2/0.2% for D-IMRT. DMLC tracking proved to be as
      efficient as standard delivery, with a two- to fivefold efficiency increase over
      gating. CONCLUSIONS: Real-time target position information was successfully
      integrated into a DMLC effector system to modify dose delivery. Experimental
      results show both comparable dosimetric accuracy as well as improved efficiency
      compared with spatial gating.

PMID- 19394161
TI  - The lateral decubitus breast boost: description, rationale, and efficacy.
AB  - PURPOSE: To describe and evaluate the modified lateral decubitus boost, a breast
      irradiation technique. Patients are repositioned and resimulated for electron
      boost to minimize the necessary depth for the electron beam and optimize target
      volume coverage. METHODS AND MATERIALS: A total of 2,606 patients were treated
      with post-lumpectomy radiation at our institution between January 1, 2000, and
      February 1, 2008. Of these, 231 patients underwent resimulation in the lateral
      decubitus position with electron boost. Distance from skin to the maximal depth
      of target volume was measured in both the original and boost plans. Age, body
      mass index (BMI), boost electron energy, and skin reaction were evaluated.
      RESULTS: Resimulation in the lateral decubitus position reduced the distance from
      skin to maximal target volume depth in all patients. Average depth reduction by
      repositioning was 2.12 cm, allowing for an average electron energy reduction of
      approximately 7 MeV. Mean skin entrance dose was reduced from about 90% to about
      85% (p < 0.001). Only 14 patients (6%) experienced moist desquamation in the
      boost field at the end of treatment. Average BMI of these patients was 30.4
      (range, 17.8-50.7). BMI greater than 30 was associated with more depth reduction
      by repositioning and increased risk of moist desquamation. CONCLUSIONS: The
      lateral decubitus position allows for a decrease in the distance from the skin to
      the target volume depth, improving electron coverage of the tumor bed while
      reducing skin entrance dose. This is a well-tolerated regimen for a patient
      population with a high BMI or deep tumor location.

PMID- 19394162
TI  - Role of adjuvant chemoradiotherapy for ampulla of Vater cancer.
AB  - PURPOSE: To evaluate the role of adjuvant chemoradiotherapy for ampulla of Vater
      cancer. METHODS AND MATERIALS: Between January 1991 and December 2002, 118
      patients with ampulla of Vater cancer underwent en bloc resection. Forty-one
      patients received adjuvant chemoradiotherapy [RT(+) group], and 77 did not [RT(-)
      group]. Postoperative radiotherapy was delivered to the tumor bed and regional
      lymph nodes, for a total dose of up to 40 Gy delivered in 2-Gy fractions, with a
      planned 2-week rest period halfway through the treatment period. Intravenous 5
      fluorouracil (500 mg/m(2)/day) was given on Days 1 to 3 of each split course. The
      median follow-up was 65 months. RESULTS: The 5-year overall survival rate in the
      RT(-) and RT(+) groups was 66.9% and 52.8%, respectively (p = 0.2225). The 5-year
      locoregional relapse-free survival rate in the RT(-) and RT(+) groups was 79.9%
      and 80.2%, respectively (p = 0.9582). When age, type of operation, T stage, N
      stage, histologic differentiation, and the use of adjuvant chemoradiotherapy were
      incorporated into the Cox proportional hazard model, there was an improvement in
      the locoregional relapse-free survival rate (p = 0.0050) and a trend toward a
      longer overall survival (p = 0.0762) associated with the use of adjuvant
      chemoradiotherapy. Improved overall survival (p = 0.0235) and locoregional
      relapse-free survival (p = 0.0095) were also evident in patients with nodal
      metastasis. In contrast, enhanced locoregional control (p = 0.0319) did not
      result in longer survival in patients with locally advanced disease (p = 0.4544).
      CONCLUSIONS: Adjuvant chemoradiotherapy may enhance locoregional control and
      overall survival in patients with ampulla of Vater cancer after curative
      resection, especially in those with nodal involvement.

PMID- 19394163
TI  - The influence of pretreatment characteristics and radiotherapy parameters on time
      interval to development of radiation-associated meningioma.
AB  - PURPOSE: To identify pretreatment characteristics and radiotherapy parameters
      which may influence time interval to development of radiation-associated
      meningioma (RAM). METHODS AND MATERIALS: A Medline/PUBMED search of articles
      dealing with RAM yielded 66 studies between 1981 and 2006. Factors analyzed
      included patient age and gender, type of initial tumor treated, radiotherapy (RT)
      dose and volume, and time interval from RT to development of RAM. RESULTS: A
      total of 143 patients with a median age at RT of 12 years form the basis of this
      report. The most common initial tumors or conditions treated with RT were
      medulloblastoma (n = 27), pituitary adenoma (n = 20), acute lymphoblastic
      leukemia (n = 20), low-grade astrocytoma (n = 19), and tinea capitis (n = 14). In
      the 116 patients whose RT fields were known, 55 (47.4%) had a portion of the
      brain treated, whereas 32 (27.6%) and 29 (25.0%) had craniospinal and whole-brain
      fields. The median time from RT to develop a RAM or latent time (LT) was 19 years
      (range, 1-63 years). Male gender (p = 0.001), initial diagnosis of leukemia (p =
      0.001), and use of whole brain or craniospinal field (p <or= 0.0001) were
      associated with a shorter LT, whereas patients who received lower doses of RT had
      a longer LT (p < 0.0001). CONCLUSIONS: The latent time to develop a RAM was
      related to gender, initial tumor type, radiotherapy volume, and radiotherapy
      dose.

PMID- 19394165
TI  - Effect of bacitracin on tetracycline resistance in Escherichia coli and
      Salmonella.
AB  - Tetracyclines and bacitracin are used extensively as a growth promotant and a
      therapeutic, respectively in livestock. In this study, we test whether there is
      an interaction between bacitracin and tetracycline that can select for an
      increase in microbial tetracycline sensitivity, using Escherichia coli and
      Salmonella as a model. We found via in vitro studies that bacitracin at sublethal
      concentrations preferentially selects for outgrowth of tetracycline-sensitive
      bacteria from among a population of tetracycline-resistant and tetracycline
      sensitive E. coli and Salmonella strains. Most of the bacterial strains employed
      in our study were shown by PCR to possess the tetracycline resistance gene tet(A)
      or tet(C), either of whose activity is associated with tetracycline efflux.
      Bacitracin could be substituted for the lipophylic chelator, fusaric acid, used
      as a positive selective agent for tetracycline sensitivity. Together, these
      observations suggest that bacitracin-mediated selection for tetracycline
      sensitivity alters the function of tetracycline efflux proteins. Using bacitracin
      and tetracycline simultaneously may improve the effectiveness of the antibiotics,
      while decreasing the risk of selecting for a population of tetracycline-resistant
      microorganisms.

PMID- 19394164
TI  - Evaluating motivational enhancement therapy adherence and competence among
      Spanish-speaking therapists.
AB  - Despite the fact that the number of Hispanic individuals in need of treatment for
      substance use problems is increasing internationally, no studies have
      investigated the extent to which therapists can provide empirically supported
      treatments to Spanish-speaking clients with adequate fidelity. Twenty-three
      bilingual Hispanic therapists from five community outpatient treatment programs
      in the United States were randomly assigned to deliver either three sessions of
      motivational enhancement therapy (MET) or an equivalent number of drug counseling
      as-usual (CAU) sessions in Spanish to 405 Spanish-speaking clients randomly
      assigned to these conditions. Independent ratings of 325 sessions indicated the
      adherence/competence rating system had good to excellent interrater reliability
      and indicated strong support for an a priori defined fundamental MET skill
      factor. Support for an advanced MET skill factor was relatively weaker. The
      rating scale indicated significant differences in therapists' MET adherence and
      competence across conditions. These findings indicate that the rating system has
      promise for assessing the performance of therapists who deliver MET in Spanish
      and suggest that bilingual Spanish-speaking therapists from the community can be
      trained to implement MET with adequate fidelity and skill using an intensive
      multisite training and supervision model.

PMID- 19394166
TI  - Expression of orexin receptors 1 (OX1R) and 2 (OX2R) in the porcine pituitary
      during the oestrous cycle.
AB  - Orexin A and B, also termed hypocretin 1 and 2, are associated with the
      stimulation of food intake and arousal. The biological actions of the hormones
      are mediated via two distinct G protein-coupled receptors, termed orexin receptor
      1 (OX1R) and orexin receptor 2 (OX2R). OX1R is selective for orexin A and OX2R
      binds orexin A and orexin B with similar affinity. The present study analyzed
      mRNA and protein expressions of OX1R and OX2R in adenohypophysis (AP) and
      neurohypophysis (NP) of cycling pigs. The tissue samples were harvested on days 2
      3, 10-12, 14-16, and 17-19 of the oestrous cycle. Using quantitative real-time
      PCR higher OX1R gene expression was detected in AP on days 2-3 relative to days
      10-12, 14-16 and 17-19 (p<0.05). In NP the OX1R mRNA level was elevated on days
      10-12 compared to the remaining stages (p<0.05). OX2R gene expression in AP was
      the lowest on days 10-12 (p<0.05 compared to days 2-3 and 17-19) and the
      expression peak occurred on days 17-19 (p<0.05 vs. the all studied stages). In NP
      the highest (p<0.05) expression of OX2R mRNA was noted on days 17-19 in relation
      to the remaining periods. OX1R protein content in AP was greatest on days 10-12
      (p<0.05), whereas in NP it was greatest on days 2-3 and 14-16 (p<0.05 vs. days 10
      12 and 17-19). In both cases the lowest OX1R protein expression was observed
      during follicular phase (p<0.05 in relation to three remaining studied stages).
      OX2R protein in AP was lower (p<0.05) on days 2-3 and 14-16 compared to days 10
      12 and 17-19. In NP the lowest (p<0.05) expression of this protein was on days 17
      19 and the highest on days 10-12 (p<0.05 compared to days 2-3 and 17-19). In
      summary, the present findings provide the first evidence that OX1R and OX2R mRNAs
      and proteins occur in the pituitary of the pig and indicate the dependence of
      orexin receptor expression on the endocrine reproductive state.

PMID- 19394167
TI  - Use of calcium supplements and the risk of coronary heart disease in 52-62-year
      old women: The Kuopio Osteoporosis Risk Factor and Prevention Study.
AB  - BACKGROUND: To analyse prospectively the effect of calcium or calcium+D
      supplementation on coronary heart disease (CHD) in 52-62-year-old women. METHODS
      AND RESULTS: 10,555 52-62-year-old women from the population-based Kuopio
      Osteoporosis Risk Factor and Prevention Study (OSTPRE) who did not have CHD at
      baseline were followed for nearly 7 years in 1994-2001. Information about use of
      calcium supplements and health events was obtained from two repeated
      questionnaires in 1989 and 1994. Information about causes of death during the
      follow-up was obtained from the Statistics Finland. Information about CHD and
      other disease morbidity before and during the follow-up was obtained from the
      Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution
      (SII). Cox's proportional-hazards models were used to estimate the risk of CHD
      morbidity related to the use of calcium supplements. At baseline, 2723 women
      reported current use of calcium or calcium+D supplementation. During the follow
      up, CHD was diagnosed in 513 women. Compared to non-users of calcium/calcium+D
      supplements, the multivariate adjusted hazard ratio (HR) of CHD was 1.24 (95% CI
      1.02-1.52) in women who used these supplements. The multivariate adjusted HR for
      CHD morbidity in postmenopausal women who used calcium/calcium+D supplements was
      1.26 (95% CI 1.01-1.57). CONCLUSIONS: Calcium or calcium+D supplementation
      appears to increase the risk of CHD among women before old age.

PMID- 19394169
TI  - Diagnostic tools for dementia.
AB  - As population ageing means that dementia is becoming more prevalent, it is
      increasingly important that clinicians from all types of practice are familiar
      with assessing patients who have possible cognitive impairment. The diagnosis of
      the syndrome of dementia remains a clinical process, supplemented by relevant
      investigations including cognitive testing. This paper reviews some of the more
      commonly used tools for assessing cognition, behaviour and overall functioning in
      patients with possible or established dementia. Several categories of instruments
      are considered, including brief screening tests, neuropsychological test
      batteries, scales for behavioural and psychiatric symptoms, and functional and
      global assessments. It is recommended that clinicians familiarize themselves with
      a small number of scales that can be readily employed in everyday practice.

PMID- 19394168
TI  - Patterns of hormone therapy use in the Norwegian Women and Cancer study (NOWAC)
      1996-2005.
AB  - OBJECTIVES: To examine patterns of use of hormone therapy (HT), including
      duration of use, in North Norway in 1996, 2002 and 2005. METHODS: Within the
      NOWAC cohort we conducted a cross-sectional comparison of questionnaire data
      among women aged 48-62 years in 1996 (N=8822), 2002 (N=6262) and 2005 (N=4830).
      Response rates for first time respondents: 58% in 1996 and 66% in 2005. The 2002
      participants were second time respondents including 4814 of the 1996
      participants. The partial dependence was managed statistically using generalized
      estimating equations (GEE) and linear mixed models. RESULTS: Use of HT increased
      from 1996 (30.5% current, 43.3% ever) to 2002 (38.2% current, 59.3% ever), and
      decreased toward 2005 (14.7% current, 35.8% ever). High-dose combinations were
      still the most used HT products in 2005, although low-dose estrogen products and
      tibolone had gained market shares. Current use of HT among pre-/perimenopausal
      women was 9.4% in 1996, 13.2% in 2002 and 0.6% in 2005. Mean duration of current
      HT use was 3.7 years in 1996, 5.8 years in 2002 and 6.3 years in 2005 (p<0.05).
      In 2005 current HT use was not associated with formerly known predictors, except
      age and menopausal status. CONCLUSIONS: Succeeding high levels of HT use in 2002,
      the prevalence in 2005 is below that in 1996, in accordance with national
      policies. In 2005 climacteric complaints seems to be the only predictor of HT
      use. Extensive long-term use in 2005 raises questions regarding compliance with
      treatment recommendations.

PMID- 19394170
TI  - Serial postmortem thoracic radiographic findings in canine cadavers.
AB  - Postmortem radiographic examinations of animals are often performed in judicial
      investigation to rule out gunshot and fractures due to cruelty. Literature
      describing postmortem changes seen on radiographs of animals is rarely available.
      Serial thoracic radiography of six recently euthanized dogs was performed in an
      interval of 8 h at a tropical ambient temperature of 22-33 degrees C. Severe
      decomposition of the cadavers prevented the study to be performed beyond 24 h.
      Gradual increment of gas accumulation in the pleural cavity, mediastinum,
      esophagus, blood vessels, cardiac chambers and subcutaneous tissue was observed.
      Lung changes observed were typical of alveolar pattern and subsequently collapsed
      secondary to severe pneumothorax. Vacuum phenomenon of the scapulohumeral joints
      which was not documented in humans was seen in four cadavers. Most radiographic
      changes were detected at 16 h post-euthanasia. Severe subcutaneous emphysema
      developed between 16 and 24 h post-euthanasia. This study showed that rapid
      postmortem changes which could be detected radiographically occur within 24 h of
      death at the ambient temperature of 22-33 degrees C.

PMID- 19394171
TI  - Self-inflicted gunshot injury simulating a criminal offence.
AB  - An extraordinary case of a young woman with a gunshot wound to her left hand is
      presented. A typical near-contact entrance wound at the palm of the hand,
      extensive soft tissue destruction including nerve and vessel injury and a large
      stellate exit wound at the back of the hand were diagnosed and surgically
      treated. The woman initially stated that she had tried to repulse the pistol when
      a man shot her from close-range, which is consistent with the injury findings.
      After questioned thoroughly, however, she confessed self-infliction using a 8 mm
      blank pistol. This case demonstrates that a self-inflicted injury simulating a
      criminal offence can be present even if very atypical features such as the use of
      a firearm and mutilating or defence-like injuries clearly speak against it.

PMID- 19394172
TI  - Age and gender differences in blood-alcohol concentration in apprehended drivers
      in relation to the amounts of alcohol consumed.
AB  - This article reports the age, gender, and blood-alcohol concentration (BAC) of
      people apprehended in Sweden for driving under the influence of alcohol (DUIA)
      over an 8-year period (2000-2007). Duplicate determinations of ethanol were made
      in venous blood by headspace gas chromatography and results were reported
      positive at a cut-off concentration of 0.1 g/L (10 mg/100 ml or 0.01 g%). The
      mean, median and highest BAC was 1.74 g/L, 1.70 g/L and 5.18 g/L, respectively.
      The vast majority of offenders were men (89.5%) with a mean age of 39.0+/-14.6 y
      (+/-SD). The women (10.5%) were a few years older 41.8+/-13.6 y (p<0.001). The
      mean BAC in the men (1.73+/-0.85 g/L) did not differ significantly (p>0.05) from
      women (1.77+/-0.87 g/L). The youngest offenders aged 15-20 y (N=3513) had a mean
      BAC of 1.30+/-0.60 g/L (median 1.32), which was significantly less (p<0.001) than
      people aged 40-50 y (N=6644); mean 1.90 g/L (median 2.0 g/L). In 95 individuals
      (89 men and 6 women) the BAC exceeded 4.0 g/L, which is a level considered to
      cause death by acute alcohol poisoning. The Widmark formula was used to calculate
      that a man (80 kg) with a BAC of 1.7 g/L has 95 g ethanol (approximately 12 units
      of alcohol) in the body compared with 61 g (approximately 8 units) for a woman
      (60 kg). This study verifies that the average drunken driver in Sweden is
      typically a binge drinker and education programs and treatment for alcohol-use
      disorder might be a more appropriate sanction than the more conventional
      penalties for alcohol-impaired driving.

PMID- 19394173
TI  - Effects of antiepileptic drugs on mRNA levels of BDNF and NT-3 and cell
      neogenesis in the developing rat brain.
AB  - Epilepsy is a common neurological disorder that occurs more frequently in
      childhood than in adulthood. Antiepileptic drugs (AEDs) which are used to treat
      seizures in pregnant women, infants, and young children may cause cognitive
      impairment or other uncertain injury. However, the exact mechanisms responsible
      for adverse effects of AEDs in the developing brain are still not clear. In the
      present study, we investigate the effects of AEDs on mRNA levels of brain-derived
      neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), cell neogenesis and mossy
      fiber sprouting (MFS) in the developing rat brain. Long-term treatment with
      Phenobarbital (40mg/kg), valproate (100mg/kg) and topiramate (40mg/kg) reduces
      BDNF and NT-3 mRNA expression in the developing brain, while lamotrigine reduces
      mRNA expression only at high dose level (80mg/kg). Cell neogenesis only increases
      in the rats treated with valproate and lamotrigine. And no differences are
      observed between the control group and the AEDs-treated groups in the Timm scores
      of the CA3 region and supragranular region. Our findings present some possible
      mechanisms to explain why different AEDs cause different cognitive impairment.

PMID- 19394174
TI  - [Bacterial meningitis as a complication of central nervous system malformations].
AB  - The diagnosis of congenital spinal or cerebral abnormality should be considered
      in any case of recurrent meningitis as well as when unusual neurological symptoms
      or cutaneous signs are present. Magnetic resonance imaging should be rapidly
      performed in order to enable an appropriate surgical management. The
      probabilistic antibiotic treatment should target anaerobic bacteria,
      Enterobacteriaceae, and Staphylococcus aureus (S. aureus).

PMID- 19394175
TI  - [Long-term follow-up of bacterial meningitis - sequels in children and adults:
      incidence, type, and assessment issues].
AB  - Bacterial meningitis remains a major cause of death and neurological and hearing
      sequels. In adults, the death rate ranges from 16 to 37% in meningitis due to
      Pneumococcus pneumoniae and neurological sequels occur in 30 to 52% of survivors.
      In childhood, the prognosis is better, with a death rate ranging from 2 to 15%,
      higher for Pneumococcus pneumoniae. Seventy-five percent of children survive
      without any sequel, 15% with hearing disorders (up to 30% with Pneumococcus), and
      rarely (3-4%) present with mental retardation, motor deficit, or epilepsy. In
      addition to the type of germ, the risk of sequels is six times higher in case of
      Pneumococcus, several factors of poor prognosis are described on admission:
      degree of coma, neurological deficit, cranial nerve palsy, high protein level,
      high erythrocytes count and low leukocytes count in CSF (less than 600 or 1000
      leukocytes per microliter). Any neurological complication such as epilepsy,
      stroke, brain edema, hydrocephalus, or hemodynamic failure will be correlated to
      a poor outcome. Hearing must be tested within 15 days, followed by audiologic
      consultation and MRI focused on labyrinths to detect early onset cochlear
      ossification. One year after meningitis, behavior and cognitive skills must be
      assessed, including IQ, memory, attention and executive functions, adaptive
      abilities, to set up specific educative and teaching strategies.

PMID- 19394176
TI  - [Contribution of microbiological methods to the diagnosis of acute bacterial
      meningitis].
AB  - The most frequent bacteria responsible for acute bacterial meningitis, after the
      neonatal period, are meningoccoci and pneumococci, very rarely Haemophilus
      influenzae and Listeria monocytogenes. The microbiological diagnosis is based on
      cell count, Gram stain, and culture of cerebrospinal fluid. Antigen detection and
      DNA detection are useful to identify the bacteria in cases of negative cultures,
      because of the fragility of some bacterial species (meningococci), or a prior
      antibiotic administration, before a lumbar puncture. Some tests for screening
      antimicrobial resistances are needed, such as those for detection of resistance
      to betalactam agents in pneumococcal isolates. Blood cultures, serum samples,
      skin rash biopsies also contribute to the diagnosis.

PMID- 19394178
TI  - [Do not biopsy pseudopapillary and solid tumors of the pancreas!].

PMID- 19394179
TI  - FDG-PET/CT: new horizons in anal cancer.
AB  - Anal cancer is an uncommon tumor with an incidence of about one case per 100,000
      in most countries. Its incidence seems to be increasing because of exposure to
      human immunodeficiency virus (HIV) and human papillomavirus (HPV). Traditional
      pretreatment evaluations include physical examination and CT imaging of the
      pelvis. Current treatment guidelines include fluorodeoxyglucose positron emission
      tomography integrated with computed tomography (FDG-PET/CT) as part of the
      standard pretreatment workup of patients diagnosed with anal cancer. At
      diagnosis, FDG-PET/CT is used to evaluate primary tumor size, lymph node status
      and to evaluate for distant metastases. FDG-PET/CT can also be used for radiation
      therapy treatment planning by clearly defining sites of metabolically active
      tumor. Posttherapy FDG-PET/CT to determine response to therapy is highly
      predictive of long-term clinical outcomes. This imaging modality can also be used
      to evaluate sites of recurrent disease. FDG-PET/CT is an imaging modality which
      greatly affects the management of patients with anal cancer.

PMID- 19394177
TI  - [Treatment of community acquired bacterial meningitis, after microbiological
      identification].
AB  - INTRODUCTION: Are the 1996 SPILF consensus conference recommendations on
      bacterial meningitis (BM) still adequate? OBJECTIVE: The literature published
      after 1996 was analyzed and the reviewers summarized the available data on
      antibiotic treatment once BM microbiological diagnosis made or strongly
      suspected. METHOD: A review was made using PubMed, 10,015 references were
      examined. Only articles published after 1997 were analyzed. RESULTS: No study
      allowed to recommend other regimens than those previously recommended in 1996, in
      case of meningococcal or pneumococcal infection: 3rd generation cephalosporin or
      amoxicillin, combined with vancomycin in case of penicillin-intermediate or
      resistant pneumococcus. In some cases, alternatives are possible, in case of
      pneumococcal infection: meropenem or antipneumococcal fluoroquinolone were
      recommended by US guidelines. New antibiotics available on the market were tested
      using experimental pneumococcal meningitis models: daptomycin and ertapenem
      seemed to be useful but linezolid was not. Among the antibiotic combinations
      tested, ceftriaxone+rifampicine demonstrated a better efficacy than
      ceftriaxone+vancomycin. There was not contributive published data on the length
      of treatment for bacterial meningitis. CONCLUSION: No assessed arguments could be
      found to modify previous guidelines. In case of problem with penicillin-resistant
      pneumococci, penem or a combination using ceftriaxone and rifampicin may be used.

PMID- 19394180
TI  - Liver and inflammatory bowel disease.
AB  - Liver disease is exceptional in patients with inflammatory bowel disease. The
      most common manifestation, sclerosing cholangitis, characterized by inflammation
      and fibrosis of the intra- and?or extrahepatic bile ducts, is unusual in patients
      with inflammatory bowel disease. Conversely, inflammatory bowel disease (mainly
      chronic ulcerative colitis) is not infrequent in patients with sclerosing
      cholangitis. Gallstone disease, portal vein thrombosis, and hepatic abscesses are
      complications directly related to inflammatory bowel disease. Drugs prescribed
      for the treatment of inflammatory bowel disease can be the cause of rare but
      potentially serious hepatic manifestations which must be recognized and detected
      early. Recent studies have demonstrated the role of purine analogues in the
      development of nodular regenerative hyperplasia. Because of the poor prognosis,
      patients taking purine analogues should be monitored regularly to search for
      inaugural signs such as an elevation of serum alkaline phosphatase or low
      platelet counts (which may not necessarily reach thrombopenia). The risk of
      methotrexate-induced fibrosis is exceptional in inflammatory bowel disease.
      Patients should be monitored with non-invasive tests to recognize the development
      of fibrosis. Finally, because of the risk of viral reactivation, patients should
      be screened for hepatitis B virus surface antigen before introducing infliximab;
      chronic carriers should be given preventive treatment with nucleoside or
      nucleotide analogues.

PMID- 19394181
TI  - Limitation for performing ultrasound-guided radiofrequency ablation of small
      renal masses.
AB  - PURPOSE: To evaluate which factor is involved in limiting ultrasound (US)-guided
      radiofrequency (RF) ablation of small renal masses. MATERIALS AND METHODS: Twenty
      five patients with 31 renal masses underwent image-guided RF ablation. If a
      lesion was visible on US, US-guided RF ablation was performed. If a lesion was
      invisible on US or if the lesion was incompletely ablated or recurred following
      US-guided RF ablation, CT-guided RF ablation was performed. We analyzed the
      various factors which were involved in US-guided RF ablation. RESULTS: Of 31
      masses, thirteen were US-visible lesions and underwent US-guided RF ablation
      whereas thirteen were US-invisible lesions and thus underwent CT-guided RF
      ablation. The remaining five lesions were US-visible but needed additional CT
      guided RF ablation, due to incomplete ablation (n=4) or recurrence (n=1); these
      renal masses (3.1+/-1.0 cm) were significantly larger than those (1.8+/-0.6 cm)
      ablated with US alone (p<0.05). Steam bubbles (4.4 cm+/-0.7 cm) of the masses
      requiring additional CT-guided RF ablation were significantly larger than those
      (2.9 cm+/-0.7 cm) of the tumors completely ablated with US alone in size
      (p<0.05). CONCLUSIONS: US-invisibility, lesion size, and steam bubbles may limit
      to perform US-guided RF ablation of small renal masses.

PMID- 19394182
TI  - Experimental intraperitoneal infusion of OK-432 in rats: evaluation of peritoneal
      complications and pathology.
AB  - PURPOSE: OK-432 is known to be a potent sclerosant of cystic lesions. The purpose
      of this study was to evaluate both its safety and pathologic effects after the
      infusion of OK-432 into the peritoneal cavity of rats. MATERIALS AND METHODS:
      Twenty male rats were used in this study. Twelve rats were infused
      intraperitoneally with 0.2 Klinishe Einheit of OK-432 melted in 2 mL of normal
      saline (group 1: the treated group); four rats each were infused
      intraperitoneally with 0.5 mL of 99% ethanol (group 2) and normal saline (group
      3), and served as the control groups. An abdominal ultrasonographic examination
      was performed both before and after the infusions in all rats. Three rats in
      group 1 and one rat in each of groups 2 and 3 were sacrificed each week following
      the infusion. Gross and microscopic evaluations of the peritoneum and abdominal
      cavity were performed on each rat. RESULTS: In group 1, the abdomen was clear on
      gross inspection and the peritoneum was unremarkable on microscopic examination.
      In group 2, mild-to-moderate peritoneal adhesions were revealed grossly, and
      inflammation and fibrosis of the peritoneum were demonstrated microscopically. In
      group 3, no specific abnormalities were noted on gross or microscopic
      examinations. CONCLUSION: Leakage or abnormal infusion of OK-432 solution into
      the peritoneal cavity during sclerotherapy of intra-abdominal or retroperitoneal
      cystic lesions does not result in any significant complications.

PMID- 19394184
TI  - Testing health literacy skills in older Korean adults.
AB  - OBJECTIVE: The purpose of this study was to develop a valid and reliable
      screening test for limited health literacy for older Korean adults. METHODS: A
      pool of 102 items was generated based on empirical referents, which, after expert
      review, field study, and content validity, was reduced to 29 items with three
      subscales. Construct validity and reliability were established using a
      convenience sample of 411 community dwelling elderly participants and exploratory
      factor analysis, and Cronbach's alpha was employed. Rasch analysis was also
      performed to assess the unidimensionality of the construct and item adequacy.
      RESULTS: Rasch analysis showed that the scale was unidimensional and the majority
      of the items demonstrated good fit. The final instrument, the Korean Health
      Literacy Scale (KHLS), is a 24-item questionnaire containing short passages,
      pictures, and graphs with multiple-choice answer format, with an internal
      consistency of .891. There are 13 comprehension and numeracy questions and 11
      questions about health-related terms; the test requires 15-20min for
      administration. CONCLUSION: KHLS is culturally suitable as a screening test for
      limited literacy for older Korean adults in the community. PRACTICE IMPLICATIONS:
      Korean investigators now have a validated health literacy tool for research with
      elderly participants.

PMID- 19394183
TI  - High spatial resolution magnetic resonance imaging of experimental cerebral
      venous thrombosis with a blood pool contrast agent.
AB  - PURPOSE: The purpose of this study was to investigate the feasibility of clot
      visualization in small sinus and cortical veins with contrast enhanced MRA in a
      cerebral venous thrombosis animal model using a blood pool contrast agent,
      Gadofosveset, and high spatial resolution imaging. MATERIAL AND METHODS: For
      induction of cerebral venous thrombosis a recently developed combined
      interventional and microsurgical model was used. Cerebral sinus and cortical vein
      thrombosis was induced in six pigs. Two further pigs died during the procedure.
      Standard structural, time-of-flight- and phase contrast-angiograms were followed
      by fast time resolved high resolution 3D MRA (4D MRA) and subsequent high spatial
      resolution 3D MRA in the equilibrium phase with and without addition of parallel
      imaging. Visualization of the clots using the different sequences was
      subjectively compared and contrast-to-noise ratio (CNR) was assessed. RESULTS: In
      the remaining six animals the procedure and MR-imaging protocol including
      administration of Gadofosveset was successfully completed. The 3D high resolution
      MRA in the equilibrium phase without the addition of parallel imaging was
      superior to all the other applied MR measurement techniques in terms of
      visualization of the clots. Only applying this sequence bridging vein thromboses
      were also seen as a small filling defect with a high CNR of >18. CONCLUSION: Only
      the non-accelerated high spatial resolution 3D MRA in the equilibrium in
      conjunction with the blood pool agent Gadofosveset allows for high-contrast
      visualization of very small clots in the cerebral sinus and cortical veins.
      STATEMENT CLINICAL IMPACT: Detection of cortical vein thrombosis is of high
      clinical impact. Conventional MRI sequences often fail to visualize the clot. We
      could demonstrate that, in contrast to conventional sequences, with high spatial
      resolution 3D MRA in the equilibrium in conjunction with the blood pool agent
      Gadofosveset very small clots in the cerebral sinus and cortical veins could be
      successfully visualized. We think that with the presented approach cortical vein
      thrombosis might also be sufficiently visualized in patients.

PMID- 19394185
TI  - Influence of triiodothyronine (T(3)) on secretion of steroids and thyroid hormone
      receptor expression in chicken ovarian follicles.
AB  - The present study was designed to (1) assess the role of triiodothyronine (T(3))
      with regard to in vitro steroid hormone secretion by chicken ovarian follicles;
      (2) determine whether T(3) influences the in vivo function of the pituitary
      ovarian axis in the hen; and (3) detect expression of thyroid hormone receptor
      (TR) mRNA in chicken ovarian follicles. In the first experiment, laying hens were
      decapitated 22.5h before ovulation. White prehierarchical follicles (1-8mm) and
      fragments of theca and granulosa layers of the 3 largest yellow preovulatory
      follicles F3-F1 (22-35mm) were incubated in a medium supplemented with T(3) (0,
      0.1, 1, 10, 100, or 1000ng/mL) or ovine luteinizing hormone (LH) (10ng/mL) in
      combination with doses of T(3) (1, 10, and 100ng/mL). Triiodothyronine decreased
      basal and LH-stimulated estradiol secretion by white follicles and the theca
      layer of all preovulatory follicles. On the other hand, it increased progesterone
      secretion by F2 and F1 follicles. In the second experiment, hens were injected 1h
      after ovulation with saline (control) or T(3) (10microg/100g body weight,
      intraperitoneally). Results indicated that exogenous T(3) decreased plasma
      concentrations of LH and estradiol and increased plasma concentrations of
      progesterone. In the third experiment, using reverse transcription polymerase
      chain reaction (RT-PCR) analysis, expression of thyroid hormone receptor (TRalpha
      and TRbeta0), mRNA was detected in all of the ovarian compartments. The
      expression of TRalpha mRNA was relatively greater in comparison with TRbeta0.
      There were no differences between white ovarian follicles in the expression of
      TRalpha and TRbeta0 mRNA. A considerably higher TRalpha and lower TRbeta0
      expression was detected in the granulosa layer of preovulatory follicles in
      comparison with the theca layer. In conclusion, the data indicate that thyroid
      hormones acting via nuclear receptors are involved in regulation of the pituitary
      ovarian axis and processes associated with follicle growth and maturation.

PMID- 19394186
TI  - Outcomes of mandated treatment for women with histories of abuse and co-occurring
      disorders.
AB  - Although there is much momentum for behavioral health policies supporting
      mandated treatment, there is little evidence supporting its safety and
      effectiveness for individuals with complex issues. The authors used a national
      study of women with co-occurring psychiatric, substance use disorders and
      histories of trauma to compare mandated and voluntary treatment by examining
      psychiatric, substance use, and trauma-related outcomes following treatment. This
      quasi-experimental study included 2,726 women, with measures completed at
      baseline, 6-month, and 12-month follow-up. Two-way analyses of covariance
      examined the main and interactive effects of coercive status (mandated vs.
      voluntary) and condition (integrated treatment vs. services as usual) on
      psychiatric distress, trauma-related symptoms, and substance use outcomes. Women
      did better with integrated treatment and with mandated treatment regardless of
      treatment condition for psychiatric, trauma, and substance use outcomes at both
      follow-ups. Further research clarifying unintended side effects and change
      mechanisms of mandated treatment is needed to inform policy decisions.

PMID- 19394188
TI  - [Revisiting case reports: a window on the care process].

PMID- 19394189
TI  - [Glucose metabolism in acute critical situation].

PMID- 19394190
TI  - [Patient dissatisfaction with postoperative pain: what are the main reasons?].
AB  - INTRODUCTION: Patient satisfaction regarding postoperative pain management (POPM)
      is not always correlated with pain level relief. OBJECTIVE: To evaluate the
      percentage of satisfied patients while splitting satisfaction related with
      nurses, anaesthesiologists and surgeons during 48h postoperative period. PATIENTS
      AND METHODS: The study was performed in 2007 by two investigators in six
      different surgical suites in a university hospital. Approximatively 15 patients
      have been randomly selected in each surgical ward. Each patient received during
      the first or second postoperative day an anonymous questionnaire and was required
      to complete it with the investigator assistance if necessary. Questions requiring
      a yes-or-no reply assessed the patient's satisfaction with POPM performed by
      nurses, surgeons, and anaesthesiologists. In case of dissatisfaction, patients
      were invited to explain the reasons. RESULTS: Ninety-two patients were included,
      5% of the patients were not satisfied with nurse POPM and nearly 15% were not
      satisfied with anaesthesiologist or surgeon POPM. The main reasons of
      dissatisfaction with nurses were the excessive delays between requesting and
      receiving an analgesic and because of the significant discrepancies in POPM
      between nurses. Patient discontent regarding surgeons was explained by the lack
      of interest of the latter for POPM. Patient discontent regarding
      anaesthesiologists was explained by the lack of anaesthesiologist visit in the
      postoperative period. CONCLUSION: There is a relationship between patient
      dissatisfaction and the lack of attention for POPM by surgeons and the lack of
      postoperative visit by the anaesthesiologist. A postoperative visit by a team of
      anaesthesia nurses should improve patient satisfaction with POPM.

PMID- 19394191
TI  - [Bronchial involvement in hypersensitivity pneumonitis].
AB  - Hypersensitivity pneumonitis is a respiratory disease resulting from the
      inhalation of antigens to which the exposed subject has been previously
      sensitized. Hypersensitivity pneumonitis is characterized by a diffuse and
      predominantly mononuclear cell inflammation of the alveolar regions that involves
      the small airways in most cases. It explains the presence of mosaic attenuation
      and expiratory air trapping at HRCT Scan. Chronic bronchitis, an obstructive
      defect at lung function tests and emphysema as long-term outcome are frequent
      consequences of this bronchial involvement.

PMID- 19394192
TI  - [Generalized convulsive status epilepticus in emergency situations in and out of
      hospital].
AB  - Generalized convulsive status epilepticus (GCSE) must be rapidly identified and
      managed according to pre-established protocols developed by the teams that treat
      such patients. Close collaboration between emergency specialists, critical-care
      specialists, electrophysiologists, and neurologists is essential. Overt GCSE, by
      far the most frequent, is generally easy to diagnose: it must nonetheless be
      distinguished from pseudo-status epilepticus. Subtle GCSE is difficult to
      recognize. The initial antiepileptic treatments are fairly well classified but
      their efficacy is unreliable. If the patient is treated within 5 to 30 minutes
      after convulsions begin, clonazepam should be administered alone; if the
      convulsions persist, follow it 5 minutes later with a second injection of
      clonazepam together with phosphenytoin or phenobarbital. If convulsions began
      more than 30 minutes before treatment, the initial clonazepam dose should be
      combined with phosphenytoin or phenobarbital. Relay antiepileptic treatment is
      essential in the short term as well, unless the cause is immediately reversible.
      This relay must be immediate if diazepam or midazolam is used alone, because of
      the high risk of recurrence. Refractory GCSE must be diagnosed very cautiously.
      Its treatment requires resuscitation using anesthetic agents guided if possible
      by continuous electroencephalography (EEG), without ever stopping the basic
      antiepileptic treatment. The cerebral aggression that results from either the
      status epilepticus itself or its cause must be treated with precision. Treatment
      of the cause is primordial and, when possible, always the main priority. The
      etiological investigation must be conducted with tenacity, speed, and
      perspicacity. GCSE may occur in known epileptics or be the first presentation.
      The investigation will be negative in 5-10% of cases. Although sometimes
      difficult to interpret, EEG is essential in numerous situations, in particular,
      atypical clinical pictures, vigilance disorders that persist after convulsions,
      and refractory status epilepticus. Overall mortality is on the order of 10%.
      Prognosis is above all a function of the cause. Age, duration of GCSE symptoms,
      and the speed and quality of management also affect prognosis. Current guidelines
      are based only very partially on data and evidence. Defining GCSE at its
      different stages is an essential prerequisite for the treatment trials that are
      necessary.

PMID- 19394193
TI  - Sub-clinical compulsive checkers show impaired performance on habitual, event-
      and time-cued episodic prospective memory tasks.
AB  - This study focused on examining whether sub-clinical checkers perform worse on a
      behavioral measure of habitual prospective memory, and on uncovering the source
      of a dissociation we previously reported between sub-clinical checkers'
      performance on event- and time-cued episodic prospective memory tasks [Cuttler,
      C., & Graf, P. (2007). Sub-clinical compulsive checkers' prospective memory is
      impaired. Journal of Anxiety Disorders, 21(3), 338-352]. Undergraduate students
      were assigned a habitual prospective memory task, an event-cued and a time-cued
      episodic prospective memory task, and they completed questionnaires designed to
      assess problems with prospective memory in everyday life. Compared to low
      checkers, high checkers demonstrated higher failure rates on the habitual, event-
      and time-cued episodic prospective memory tasks, and reported more frequent
      failures of prospective memory in everyday life. The results showed that the
      previously reported dissociation was an artifact of the method used for scoring
      time-cued prospective memory. Our results lend support to the theory that a
      deficit in prospective memory contributes to the development and maintenance of
      checking compulsions.

PMID- 19394194
TI  - Comparing different short-term service delivery methods of visual-motor treatment
      for first grade students in mainstream schools.
AB  - To compare the efficacy of three different short-term service delivery methods on
      first grade children with soft neurological signs who suffer from visual-motor
      difficulties. One hundred and forty seven first grade students who scored below
      the 21st percentile on the Visual-Motor Integration Test (VMI) were recruited
      from schools and randomly divided into three intervention groups and an
      additional control group. One group received Direct Treatment Model (DT), the
      second group received Collaborative-Consultation Treatment Model (CC) and the
      third group received a Combined Treatment Model (CT). The CC included treatment
      administered by teachers, after Collaborative-Consultation with an occupational
      therapist (OT). The CT included the two models (DT, CC), administered
      simultaneously. Pre- and post-intervention tests were administered to both
      groups. Students in all three intervention groups made significant gains in
      comparison to the control group suggesting that all three service delivery
      methods had the same effect on children's visual-motor skills. Therapists in
      school settings who are obliged to be more efficient are encouraged to use the CC
      or the CT service delivery methods which would enable them to treat more children
      during the same time-frame, with full confidence that the treatment goals will be
      achieved as if using the DT.

PMID- 19394196
TI  - Long-lasting neurosensory disturbance following advancement of the retrognathic
      mandible: distraction osteogenesis versus bilateral sagittal split osteotomy.
AB  - Neurosensory disturbance (NSD) of the inferior alveolar nerve (IAN) is the most
      common complication after bilateral sagittal split osteotomy (BSSO) and
      distraction osteogenesis (DO) of the retrognathic mandible. It is suggested that
      the risk is lower after DO than after BSSO. This retrospective study compared
      both techniques with regard to long-lasting NSD and overall patient satisfaction.
      91 patients (representing 182 IANs) were included, they completed a questionnaire
      and underwent an objective neurosensory test. In the BSSO-group (90 nerves), long
      lasting NSD was reported in 27 cases (30%) versus 21 cases (23%) in the DO group
      (92 nerves). In 39 cases (24 BSSO, 15 DO) the long-lasting NSD was reported in
      the lower lip, the chin or both. Of these cases, 9 (5 BSSO, 4 DO) were
      objectively tested positive. The overall prevalence was 8% in the BSSO group and
      10% in the DO group. There was no significant difference in subjectively reported
      and objectively measured NSD between the groups. In this study patients seemed to
      over-report the NSD compared with the objective findings. For both procedures,
      overall patient satisfaction was high.

PMID- 19394197
TI  - Tooth section technique for wisdom teeth.

PMID- 19394195
TI  - The effect of vibration on postural response of Down syndrome individuals on the
      seesaw.
AB  - In order to better understand the role of proprioception in postural adjustments
      on unstable surfaces, we analyzed the effect of vibration on the pattern of
      muscle activity and joint displacements (ankle, knee and hip) of eight
      intellectually normal participants (control group-CG) and eight individuals with
      Down syndrome (DS) while balancing on seesaws of different heights. The
      individuals with DS adopted a pattern of co-contraction and were not able to
      modulate the magnitude of postural response with the seesaw's height. The
      vibration affected neither the ability of individuals with DS to maintain balance
      nor the pattern of muscle contraction. On the other hand the control group
      changed the strategy with vibration, adopting one similar to that used by
      individuals with DS. Collectively, our findings suggest that proprioceptive
      information is essential for the motor control system to select the appropriate
      motor strategy of reciprocal activation among the agonist and antagonist to
      efficiently balance. Also, these findings suggest that a proprioceptive deficit
      could explain the atypical motor strategy observed in individuals with DS during
      balance on seesaw.

PMID- 19394198
TI  - Dynamic statistical parametric mapping for analyzing ictal
      magnetoencephalographic spikes in patients with intractable frontal lobe
      epilepsy.
AB  - The purpose of this study is to assess the clinical value of spatiotemporal
      source analysis for analyzing ictal magnetoencephalography (MEG). Ictal MEG and
      simultaneous scalp EEG was recorded in five patients with medically intractable
      frontal lobe epilepsy. Dynamic statistical parametric maps (dSPMs) were
      calculated at the peak of early ictal spikes for the purpose of estimating the
      spatiotemporal cortical source distribution. DSPM solutions were mapped onto a
      cortical surface, which was derived from each patient's MRI. Equivalent current
      dipoles (ECDs) were calculated using a single-dipole model for comparison with
      dSPMs. In all patients, dSPMs tended to have a localized activation, consistent
      with the clinically determined ictal onset zone, whereas most ECDs were
      considered to be inappropriate sources according to their goodness-of-fit values.
      Analyzing ictal MEG spikes by using dSPMs may provide useful information in
      presurgical evaluation of epilepsy.

PMID- 19394199
TI  - Reciprocal regulation of LOX and LOXL2 expression during cell adhesion and
      terminal differentiation in epidermal keratinocytes.
AB  - BACKGROUND: Classical lysyl oxidase (LO) is involved in the stabilization and
      repair of extracellular matrix by the oxidization of lysine residues in collagen
      and elastin. Five genetically distinct species of LOs (LOX and LOXL1-4) have been
      identified, but their functions remain unclear. OBJECTIVES: To investigate the
      regulation of LOs during differentiation and cell adhesion of cultured
      keratinocytes. METHODS: LO mRNA and polypeptides levels in the suspension and
      adhesive cultures were measured using real-time PCR, immunoblot and
      immunofluorescence assays. Localization of LOX, LOXL1 and LOXL2 gene transcripts
      in normal epidermis was assessed by in situ hybridization. RESULTS: In the
      epidermis and cultured keratinocytes, LOX, LOXL1 and LOXL2 mRNA levels were
      predominant, and LOXL3 and LOXL4 were minor components. When cultured
      keratinocytes were induced to terminal differentiation, LOX expression increased
      12-fold and LOXL2 expression decreased 0.1-fold, while LOXL1 mRNA level was
      essentially unchanged. When growth-arrested cells were allowed to adhere to
      extracellular matrices, LOXL2 mRNA level was stimulated 7-fold by fibronectin or
      type IV collagen substrate, whereas LOX mRNA level was decreased 0.1-fold by all
      substrates tested. Reciprocal regulation of LOX and LOXL2 expression during
      differentiation and adhesion was confirmed by immunoblot analysis and double
      immunofluorescent observation of cultured cells using anti-LOX and anti-LOXL2
      antibodies. In situ hybridization analysis of normal epidermis revealed LOXL2
      mRNA mainly in the lower epidermis, LOX mRNA in the upper layer of epidermis and
      LOXL1 throughout the epidermis. CONCLUSION: LOX expression in cultured
      keratinocytes is related to keratinization whereas LOXL2 expression is related to
      cell-matrix interaction.

PMID- 19394200
TI  - Gene expression in canine atopic dermatitis and correlation with clinical
      severity scores.
AB  - BACKGROUND: Canine atopic dermatitis (cAD) is a common condition in dogs that may
      be a naturally occurring model for human atopic dermatitis (hAD). Despite this,
      comparative research is limited, particularly into the genetic background of cAD.
      OBJECTIVES: 1. Measure candidate gene expression in cAD skin using quantitative
      real time PCR (qPCR). 2. Correlate gene expression to clinical cAD scores (Canine
      Atopic Dermatitis Extent and Severity Index[CADESI]-03 and intradermal allergen
      test [IDT]). METHODS: mRNA was extracted from biopsies of non-lesional and
      lesional skin from atopic dogs, and healthy skin from non-atopic dogs. Gene
      expression was quantified using qPCR, and compared between non-lesional atopic,
      lesional atopic and healthy skin. Gene expression in atopic skin was correlated
      with clinical severity (CADESI-03) and the number of positive reactions on an
      IDT. RESULTS: Of the 20 quantified genes, 11 demonstrated statistically
      significant altered mRNA expression between atopic and healthy skin; dipeptidyl
      peptidase-4 (DPP4), phosphatidylinositol-3,4,5-trisphosphate-5-phosphatase-2
      (INPPL1), serine protease inhibitor kazal type-5 (SPINK5), sphingosine-1
      phosphate lyase-1 (SGPL1), peroxisome proliferator-activated receptor gamma
      (PPARgamma), S100 calcium-binding protein A8 (S100A8), Plakophilin-2 (PKP2),
      Periostin (POSTN), Cullin4A, TNF-alpha and metalloproteinase inhibitor-1 (TIMP
      1). Three genes correlated with CADESI-03: serum amyloid A 1 (SAA-1), S100A8, and
      PKP2; and four with IDT results: mast cell protease I (CMA1), SAA-1, S100A8 and
      SPINK5. CONCLUSION: Genes with altered expression included those relevant to skin
      barrier formation and immune function, suggesting both are relevant in the
      pathogenesis of AD. Many of these genes reflect the proposed pathogenesis in hAD,
      supporting the use of dogs as a model for hAD. Furthermore, these genes may be
      considered suitable targets for future genetic and protein function studies in
      human and canine AD.

PMID- 19394202
TI  - OXA-23-type imipenem resistance in Acinetobacter baumannii in Hong Kong.

PMID- 19394201
TI  - A new homodimer of aciclovir as a prodrug with increased solubility and antiviral
      activity.
AB  - Aciclovir (ACV) is the drug of choice against herpes simplex virus type 1 (HSV-1)
      infection. However, its limited solubility in water and limited oral
      bioavailability represent the main limitations of this drug. Utilising a plaque
      reduction assay, this study assessed the antiherpetic activity of a new homodimer
      of ACV (ACVp(2)ACV) with a higher water solubility. ACVp(2)ACV markedly inhibited
      HSV-1 replication in Vero cells [50% effective concentration (EC(50)) of 2.8
      microM vs. 6.6 microM for ACV] and was non-toxic in the cells at concentrations
      <or= 15 microM. ACVp(2)ACV encapsulated in erythrocytes provides effective
      protection against HSV-1 replication in human macrophages and also partially
      against the HSV-1 thymidine kinase-deficient strain. Thus, ACVp(2)ACV acts as an
      effective antiviral prodrug against HSV-1.

PMID- 19394203
TI  - In vivo efficacy of sitafloxacin in a new murine model of non-typeable
      Haemophilus influenzae pneumonia by sterile intratracheal tube.
AB  - A novel murine model of non-typeable Haemophilus influenzae (NTHi) pneumonia was
      established. A plastic tube was inserted into the trachea 7 days before bacterial
      inoculation. Numbers of NTHi recovered from the lungs and trachea were determined
      for 7 days. Histologically, bronchioles and adjacent alveoli in the intubation
      group were filled with numerous inflammatory cells. The efficacy of sitafloxacin
      was compared with ciprofloxacin using the new murine pneumonia model. The data
      suggest that sitafloxacin displays equivalent efficacy to ciprofloxacin against
      H. influenzae pneumonia. This new murine NTHi pneumonia model appears useful not
      only for in vivo evaluation of antibiotics but also for analysis of the
      pathogenesis of H. influenzae pneumonia.

PMID- 19394204
TI  - Modulation of sickness behavior by sleep: the role of neurochemical and
      neuroinflammatory pathways in mice.
AB  - Activation of the immune system elicits several behavioral changes that are
      collectively called sickness behavior and consists in a strategy to overcome
      infection. Sleep deprivation can increase susceptibility to pathogens and to
      behavioral alterations. Thus, the present study aimed to determine how
      paradoxical sleep deprivation (PSD) affects the behavioral and neurochemical
      responses to lipopolysaccharide (LPS, potent activator of the immune response).
      Adult inbred mice were paradoxical sleep deprived (72 h), whereas the control
      group was kept in their home cages. Both groups received either an injection of
      saline or LPS (5, 10 or 20 microg/animal ip) before behavioral tasks and tissue
      collection. During the recovery sleep period, LPS provoked a strong inhibition of
      sleep rebound due to a suppression of paradoxical sleep. PSD increased the
      susceptibility of mice to LPS-induced immobility in the open field, which was
      capable of affecting the anxiety-like behavior also. These altered behavioral
      responses to LPS were accompanied by reduction in dopamine turnover within the
      striatum and increased expression of cyclooxygenase-2 in the cortex. The study
      provides some insights into how the sleep-wake cycle affects the expression of
      sickness behavior induced by LPS.

PMID- 19394206
TI  - Rapid screening of surfactant and biosurfactant surface cleaning performance.
AB  - Surface Plasmon Resonance (SPR) and rubisco protein stain were used as tools to
      screen the effectiveness of detergent formulations in cleaning a protein stain
      from solid surfaces. Surfactant and biosurfactant-based formulations, with and
      without added protease, were screened for cleaning performance. Enzyme-free
      detergent formulations at 1500 ppm total surfactant were insufficient to cause
      complete surface cleaning, despite the high concentration of surfactant. The
      cleaning performance of a "home-made" formulation containing 2 ppm subtilisin A
      (SA) and 2 ppm sodium dodecyl benzyl sulphonate (SDOBS) was as efficient as the
      best amongst the three enzyme-free 1500 ppm formulations. The cleaning
      performance of 2 ppm SA in the absence of SDOBS was less effective than the
      combined formulation, even though 2 ppm SDOBS alone did not cause any protein
      removal. The observed synergistic performance was attributed to the cooperative
      mechanisms (chemical and physical attack) by which these two agents act on a
      rubisco stain. Replacing SDOBS in the enzyme-surfactant formulation with the same
      amount of surfactin biosurfactant (2 ppm) gave the best rubisco removal of all
      formulations examined in this study, irrespective of the surface chemistry
      underlying the protein film. It was found that 75% and 80% of immobilised rubisco
      stain could be removed from hydrophobic and hydrophilic surfaces, respectively,
      by the biosurfactant-SA formulation (compared with 60% and 65%, respectively,
      using the SDOBS-SA formulation). Our results suggest that it may be possible to
      generate fully renewable biochemical-based cleaning formulations that have
      superior cleaning performance to existing technologies. In developing optimised
      formulations, there is a pressing need for chip-based tools similar to that
      developed in this research.

PMID- 19394205
TI  - Neural correlates of emotion processing in borderline personality disorder.
AB  - Emotional instability is a hallmark feature of borderline personality disorder
      (BPD), yet its biological underpinnings are poorly understood. We employed
      functional magnetic resonance imaging (fMRI) to compare patterns of regional
      brain activation in BPD patients and healthy volunteers as they process positive
      and negative social emotional stimuli. fMRI images were acquired while 19 BPD
      patients and 17 healthy controls (HC) viewed emotion-inducing pictures from the
      International Affective Pictures System set. Activation data were analyzed with
      SPM5 ANCOVA models to derive the effects of diagnosis and stimulus type. BPD
      patients demonstrated greater differences in activation than controls, when
      viewing negative pictures compared with rest, in the amygdala, fusiform gyrus,
      primary visual areas, superior temporal gyrus (STG), and premotor areas, while
      healthy controls showed greater differences than BPD patients in the insula,
      middle temporal gyrus and dorsolateral prefrontal cortex (BA46). When viewing
      positive pictures compared with rest, BPD patients showed greater differences in
      the STG, premotor cortex, and ventrolateral prefrontal cortex. These findings
      suggest that BPD patients show greater amygdala activity and heightened activity
      of visual processing regions relative to findings for HC subjects in the
      processing of negative social emotional pictures compared with rest. The patients
      activate neural networks in emotion processing that are phylogeneticall older and
      more reflexive than those activated by HC subjects.

PMID- 19394207
TI  - Preparation and characterization of thermo-responsive amphiphilic triblock
      copolymer and its self-assembled micelle for controlled drug release.
AB  - An amphiphilic thermo-responsive ABA triblock copolymer, poly(methyl
      methacrylate)-b-poly(N-isopropylacrylamide-co-poly(ethylene-glycol) methyl ether
      methacrlate)-b-poly(methyl methacrylate) (PMMA-b-P(NIPAM-co-PEGMEMA)-b-PMMA), was
      designed and synthesized via reversible addition fragmentation chain transfer
      (RAFT) polymerization, and subsequently characterized by FT-IR, (1)H NMR and GPC.
      The copolymer can disperse in water and self-assemble into nanoscaled micelles in
      a "flower-like" arrangement at room temperature; the hydrophobic PMMA tucks in
      the core while the hydrophilic and improved biocompatible P(NIPAM-co-PEGMEMA)
      forms a thermosensitive outer shell. The resulting micelles were investigated
      using fluorescence spectroscopy, dynamic light scattering technique (DLS) and
      transmission electron microscopy (TEM). The copolymer exhibited a lower critical
      solution temperature (LCST) of around 39 degrees C via optical transmittance
      measurements. Notably, there was no copolymer precipitation observed at the LCST,
      which was propitious to in vivo use of the micelle. The micelles loaded with
      folic acid as a model drug showed a desired thermo-responsive drug release
      behavior. It was found that the rate and amount (maximum percentage 85%) of the
      drug release was much higher above the LCST than that (maximum percentage 36%)
      below the LCST. These results indicate that the thermosensitive triblock
      copolymer possesses promising potential applications as a "smart" drug carrier in
      biomedical science.

PMID- 19394208
TI  - Protective effects of purified safflower extract on myocardial ischemia in vivo
      and in vitro.
AB  - Carthamus tinctorius L. (safflower) is one of the most commonly used Chinese
      herbal medicines to prevent and treat cardiac disease in clinical practice.
      However, the mechanisms responsible for such protective effects remain largely
      unknown. In this study, we investigated the anti-myocardial ischemia effects of a
      purified extract of C. tinctorius (ECT) both in vivo and in vitro. An animal
      model of myocardial ischemia injury was induced by left anterior descending
      coronary artery occlusion in adult rats. Pretreatment with ECT (100, 200, 400,
      600 mg/kg body wt.) could protect the heart from ischemia injury by limiting
      infarct size and improving cardiac function. In the in vitro experiment, neonatal
      rat ventricular myocytes were incubated to test the direct cytoprotective effect
      of ECT against H(2)O(2) exposure. Pretreatment with 100-400 microg/ml ECT prior
      to H(2)O(2) exposure significantly increased cell viability as revealed by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. ECT also
      markedly attenuated H(2)O(2)-induced cardiomyocyte apoptosis, as detected by
      Annexin V and PI double labeling with flow cytometry. The intracellular level of
      reactive oxygen species (ROS) was shown by 2',7'-dichlorofluorescin diacetate
      (DCFH-DA), and ECT pretreatment significantly inhibited H(2)O(2)-induced ROS
      increase. We made a preliminary examination of the signaling cascade involved in
      ECT mediated anti-apoptotic effects. Phosphatidylinositol 3 kinase (PI3K)
      inhibitor (LY294002) blocked the cytoprotective effect conferred by ECT. Taken
      together, our findings provide the first evidence that the cardioprotective
      effects of ECT in myocardial ischemia operate partially through reducing
      oxidative stress induced damage and apoptosis. The protection is achieved by
      scavenging of ROS and mediating the PI3K signaling pathway.

PMID- 19394209
TI  - Clinical commentary --COPD is not a systemic disease. Results from the AIMAR
      Expert Opinion Consensus/Dissensus Seminar "COPD is/is not a systemic disease?",
      Venice, Italy, 13-14 November 2008.
AB  - Although COPD is a major disease worldwide there is a perplexing current
      uncertainty about the nature of this disease. COPD is characterized at onset and
      prevalently by the involvement of the lungs and bronchi, but as the disease
      evolves abnormalities develop in other organs and systems and the question
      arises: what is the pathogenesis of these respiratory and systemic impairments?
      Are the alterations that occur outside the respiratory system in the course of
      COPD a direct consequence of the lung pathology or is the lung simply the local
      expression of a pathological event whose origin lies in the organism as a whole?
      To tease out this issue, the Expert Opinion Consensus/Dissensus Seminar "COPD
      is/is not a systemic disease?" took place in Venice, on 13-14 November 2008. The
      Seminar was conceived and organized by the Italian Interdisciplinary Association
      for Research in Lung Disease, AIMAR. Top international opinion leaders in the
      respiratory field were invited to participate, the aim being to bring together
      sustainers of the two sides in a format allowing the best opportunity for an in
      depth debate. Over the two days, different aspects of the issue 'upstream'
      (pathophysiology and biology) and 'downstream' (treatment and outcome assessment)
      were discussed. The general consensus that emerged, based on the still limited
      evidence available, was that COPD begins as a local inflammation in the lungs and
      this leads - through differentiated pathways yet to be fully clarified - to
      systemic consequences.

PMID- 19394211
TI  - On vesicle formation and tethering in the ER-Golgi shuttle.
AB  - Transport in the ER-Golgi shuttle is performed by COPII in the anterograde and by
      COPI in the retrograde direction. How these transport steps are regulated and
      which mechanisms act to balance the vesicle flow between the ER and the Golgi
      apparatus are the issues currently under investigation. The elucidation of the
      structures of COPII components and tethers for COPI and COPII vesicles, together
      with detailed biochemical and cell biological analysis over the past few years
      greatly increased our knowledge on how vesicles are formed, not only at the ER
      and the Golgi but also at other organelles and the plasma membrane by analogy.
      Moreover, recent work provided more than just a glimpse on the function of
      tethering proteins at arrival sites on the ER and the Golgi. Most likely,
      organized exit and arrival sites exist at each vesicular transport step along the
      exocytic and endocytic routes.

PMID- 19394210
TI  - Polysomes, P bodies and stress granules: states and fates of eukaryotic mRNAs.
AB  - The control of translation and mRNA degradation plays a key role in the
      regulation of eukaryotic gene expression. In the cytosol, mRNAs engaged in
      translation are distributed throughout the cytosol, while translationally
      inactive mRNAs can accumulate in P bodies, in complex with mRNA degradation and
      translation repression machinery, or in stress granules, which appear to be mRNAs
      stalled in translation initiation. Here we discuss how these different granules
      suggest a dynamic model for the metabolism of cytoplasmic mRNAs wherein they
      cycle between different mRNP states with different functional properties and
      subcellular locations.

PMID- 19394212
TI  - Grafting of molecularly imprinted polymers on iniferter-modified carbon nanotube.
AB  - Molecularly imprinted polymers (MIPs) were grafted on iniferter-modified carbon
      nanotube (CNT). Tween 20 was first immobilized on CNT by hydrophobic
      interactions. The hydroxyl-functionalized CNT was modified by silanisation with 3
      chloropropyl trimethoxysilane. The iniferter groups were then introduced by
      reacting the CNT-bound chloropropyl groups with sodium N,N
      diethyldithiocarbamate. UV light-initiated copolymerization of ethylene glycol
      dimethacrylate (crosslinking agent) and methacrylic acid (functional monomer)
      resulted in grafting of MIP on CNT for theophylline as a model template. MIPs
      grafted on CNT were characterized with elemental analysis, scanning electron
      microscopy, and thermogravimetric analysis. The theophylline-imprinted polymer on
      CNT showed higher binding capacity for theophylline than non-imprinted polymer on
      CNT and selectivity for theophylline over caffeine and theobromine (similar
      structure molecules). The data of theophylline and caffeine binding into the
      theophylline-imprinted polymer correlated well with the Scatchard plot. These
      MIPs on CNT can potentially be applied to probe materials in biosensor system
      based on CNT field effect transistor.

PMID- 19394214
TI  - Looking past the model species: diversity in gaze-following skills across
      primates.
AB  - Primates must navigate complex social landscapes in their daily lives: gathering
      information from and about others, competing with others for food and mates, and
      cooperating to obtain rewards as well. Gaze-following often provides important
      clues as to what others see, know, or will do; using information about social
      attention is thus crucial for primates to be competent social actors. However,
      the cognitive bases of the gaze-following behaviors that primates exhibit appear
      to vary widely across species. The ultimate challenge of such analyses will
      therefore be to understand why such different cognitive mechanisms have evolved
      across species.

PMID- 19394213
TI  - Nonspecific-adsorption behavior of polyethylenglycol and bovine serum albumin
      studied by 55-MHz wireless-electrodeless quartz crystal microbalance.
AB  - The nonspecific binding ability of polyethylenglycol (PEG) and bovine serum
      albumin (BSA) on modified and unmodified surfaces is quantitatively studied by a
      wireless-electrodeless quartz crystal microbalance (WE-QCM). PEG and BSA are
      important blocking materials in biosensors, but their affinities for proteins and
      uncoated substrates have not been known quantitatively. The WE-QCM allows
      quantitative analysis of the adsorption behavior of proteins on the electrodeless
      surfaces. Affinities of PEG, BSA, human immunoglobulin G (hIgG), and
      Staphylococcus protein A (SPA) for alpha-SiO(2)(quartz), Au thin film, PEG, and
      BSA are systematically studied by the homebuilt flow-injection system. PEG shows
      low affinities for the SiO(2) surface (K(A)=4.2x10(4) M(-1)) and the Au surface
      (K(A)=6.6x10(4) M(-1)), but BSA shows higher affinity for the SiO(2) surface
      (K(A)=1.4x10(6) M(-1)). Both PEG and BSA show low affinities for hIgG (K(A)
      approximately 1.5x10(5) M(-1)). However, the number of binding sites of PEG to
      hIgG is significantly larger than that of BSA, indicating that blocking for hIgG
      is favorably achieved by BSA, rather than PEG.

PMID- 19394215
TI  - Lactic acid production by Lactobacillus sp. RKY2 in a cell-recycle continuous
      fermentation using lignocellulosic hydrolyzates as inexpensive raw materials.
AB  - Continuous lactic acid fermentations were conducted using lignocellulosic
      hydrolyzates and corn steep liquor as inexpensive raw materials. Lactic acid
      concentrations decreased with increases in the dilution rate, whereas the
      residual substrate concentrations increased. However, lactic acid yields were
      maintained at more than 0.90 g g(-1) over all cases experimented. The cell
      recycle cultivation system exerted positive effects on fermentation efficiency,
      including volumetric productivity, which is attributable to the retention of
      cells in the bioreactor. The cell-recycle continuous fermentation of
      lignocellulosic hydrolyzates yielded a lactic acid productivity of 6.7 g l(-1) h(
      1) for a dilution rate of 0.16 h(-1) using 30 g l(-1) of corn steep liquor and
      1.5 g l(-1) of yeast extract as nutrients. The productivity (6.7 g l(-1) h(-1))
      acquired by the cell-recycle continuous fermentation of lignocellulosic
      hydrolyzates was 1.6 times higher than the lactic acid productivity yielded in
      the continuous fermentation without cell-recycle system.

PMID- 19394216
TI  - Synthesis of phenylisothiourea derivatives as inhibitors of NO production in LPS
      activated macrophages.
AB  - A series of phenylisothioureas were synthesized as inhibitors of NO production in
      lipopolysaccharide-activated macrophages. We investigated the effect of
      lipophilic moiety and N- or S-substituents of the phenylisothioureas on the
      activity. Inhibitory activities of carbazole-linked phenylisothioureas were
      superior to the corresponding simple phenylisothiourea derivatives. Among these
      compounds, 12b having N-ethyl and S-isopropyl groups on phenylisothiourea moiety
      was the most potent in the inhibition of NO production. They inhibited NO
      production through the suppression of the LPS-induced translocation of p65
      subunit of NF-kappaB and the followed suppression of the iNOS protein and mRNA
      expression.

PMID- 19394217
TI  - 2-Cyclohexylcarbonylbenzimidazoles as potent, orally available and brain
      penetrable opioid receptor-like 1 (ORL1) antagonists.
AB  - The synthesis and biological evaluation of new potent opioid receptor-like 1
      (ORL1) antagonists are presented. Conversion of the thioether linkage of the
      prototype [It is reported prior to this communication as a consecutive series.:
      Kobayashi, K.; Kato, T.; Yamamoto, I.; Shimizu, A.; Mizutani, S.; Asai, M.;
      Kawamoto, H.; Ito, S.; Yoshizumi, T.; Hirayama, M.; Ozaki, S.; Ohta, H.; Okamoto,
      O. Bioorg. Med. Chem. Lett., in press] to the carbonyl linker effectively reduces
      susceptibility to P-glycoprotein (P-gp) efflux. This finding led to the
      identification of 2-cyclohexylcarbonylbenzimizole analogue 7c, which exhibited
      potent ORL1 activity, excellent selectivity over other receptors and ion
      channels, and poor susceptibility to P-gp. Compound 7c also showed satisfactory
      pharmacokinetic profiles and brain penetrability in laboratory animals.
      Furthermore, 7c showed good in vivo antagonism. Hence, 7c was selected as a
      clinical candidate for a brain-penetrable ORL1 antagonist.

PMID- 19394218
TI  - Synthesis of aristolactam analogues and evaluation of their antitumor activity.
AB  - A series of natural aristolactams and their analogues have been prepared and
      evaluated for antitumor activity against human cancer cells, including multi-drug
      resistant cell lines. Naturally occurring aristolactams, such as aristolactam BII
      (cepharanone B), aristolactam BIII, aristolactam FI (piperolactam A), N-methyl
      piperolactam A, and sauristolactam showed moderate antitumor activities in
      selected cell lines. However, several synthetic aristolactam derivatives
      exhibited potent antitumor activities against a broad array of cancer cell lines
      with GI(50) values in the submicromolar range.

PMID- 19394219
TI  - Orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors.
AB  - We discovered a structurally novel SCD (Delta9 desaturase) inhibitor 4a (CVT
      11,563) that has 119 nM potency in a human cell-based (HEPG2) SCD assay and
      selectivity against Delta5 and Delta6 desaturases. This compound has 90% oral
      bioavailability (rat) and excellent plasma exposure (dAUC 935 ng h/mL).
      Additionally, 4a shows moderately selective liver distribution (three times vs
      plasma and adipose tissue) and relatively low brain penetration. In a five-day
      study (high sucrose diet, rat) compound 4a significantly reduced SCD activity as
      determined by GC analysis of fatty acid composition in plasma and liver. We
      describe the discovery of 4a from HTS hit 1 followed by scaffold replacement and
      SAR studies focused on DMPK properties.

PMID- 19394220
TI  - Potent and selective alpha1A adrenoceptor partial agonists--novel imidazole
      frameworks.
AB  - Novel imidazole frameworks have been identified as potent partial agonists of the
      alpha(1A) adrenergic receptor, with good selectivity over the alpha(1B),
      alpha(1D) and alpha(2A) receptor sub-types. Nitrile 28 possessed attractive CNS
      drug-like properties with good membrane permeability and no P-pg mediated efflux.
      28 also possessed excellent solubility, metabolic stability and wide ligand
      selectivity.

PMID- 19394221
TI  - Application of combinatorial biocatalysis for a unique ring expansion of
      dihydroxymethylzearalenone.
AB  - Combinatorial biocatalysis was applied to generate a diverse set of
      dihydroxymethylzearalenone analogs with modified ring structure. In one
      representative chemoenzymatic reaction sequence, dihydroxymethylzearalenone was
      first subjected to a unique enzyme-catalyzed oxidative ring opening reaction that
      creates two new carboxylic groups on the molecule. These groups served as
      reaction sites for further derivatization involving biocatalytic ring closure
      reactions with structurally diverse bifunctional reagents, including different
      diols and diamines. As a result, a library of cyclic bislactones and bislactams
      was created, with modified ring structures covering chemical space and structure
      activity relationships unattainable by conventional synthetic means.

PMID- 19394222
TI  - Novel carbazole and acyl-indole antimitotics.
AB  - In the course of our Heat Shock 90 program, certain carbazole compounds were
      identified which had an off-target antiproliferative activity. To understand the
      off-target activity, we studied one analog with strong activity. We discovered
      that it had an effect on tubulin polymerization kinetics and was competitive with
      colchicine. Additional analogs were made, and a number of potent compounds were
      identified.

PMID- 19394223
TI  - Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of
      the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase.
AB  - Exploration of the SAR around a series of 3,5-disubstituted-1H-pyrrolo[2,3
      b]pyridines led to the discovery of novel pyrrolopyridine inhibitors of the IGF
      1R tyrosine kinase. Several compounds demonstrated nanomolar potency in enzyme
      and cellular mechanistic assays.

PMID- 19394224
TI  - Regioselective preparation of 5-hydroxypropranolol and 4'-hydroxydiclofenac with
      a fungal peroxygenase.
AB  - An extracellular peroxygenase of Agrocybe aegerita catalyzed the H(2)O(2)
      dependent hydroxylation of the multi-function beta-adrenergic blocker propranolol
      (1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol) and the non-steroidal anti
      inflammatory drug diclofenac (2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid)
      to give the human drug metabolites 5-hydroxypropranolol (5-OHP) and 4'
      hydroxydiclofenac (4'-OHD). The reactions proceeded regioselectively with high
      isomeric purity and gave the desired 5-OHP and 4'-OHD in yields up to 20% and
      65%, respectively. (18)O-labeling experiments showed that the phenolic hydroxyl
      groups in 5-OHP and 4'-OHD originated from H(2)O(2), which establishes that the
      reaction is mechanistically a peroxygenation. Our results raise the possibility
      that fungal peroxygenases may be useful for versatile, cost-effective, and
      scalable syntheses of drug metabolites.

PMID- 19394227
TI  - Cardiac surgery: 25 years on.

PMID- 19394226
TI  - Perceptions of registered and enrolled nurses on thirst in mechanically
      ventilated adult patients in intensive care units-a phenomenographic study.
AB  - BACKGROUND: Thirst is a commonly experienced source of discomfort among patients
      receiving mechanical ventilation during intensive care. Dehydration, endotracheal
      tubes, electrolyte disturbances and the use of various medicines can contribute
      to the feeling of thirst. At present, the knowledge of nurses' perceptions of the
      feelings of thirst in mechanically ventilated patients are limited. PURPOSE: The
      purpose of this study was to describe registered and enrolled intensive care
      nurses' perceptions of the feelings of thirst in mechanically ventilated adult
      patients and to investigate the interventions to reduce thirst. METHOD: Ten
      registered intensive care nurses and 10 enrolled nurses, aged 32-59 years, were
      interviewed. They all had at least one year's experience in caring for adult,
      mechanically ventilated patients. The data were analysed using a phenomenographic
      methodology. FINDINGS: Four categories of perceptions among registered and
      enrolled nurses, regarding thirst in mechanically ventilated patients were
      identified: reasons for thirst, signs of thirst, preventing or reducing thirst
      and the perception that patients had no feelings of thirst. CONCLUSIONS:
      Registered and enrolled nurses wish to reduce sources of discomfort among their
      patients but they do not always realise that patients feel thirst and therefore
      relieving it has a low priority among staff. Relieving thirst is a human need
      that must be recognised in nursing education and on intensive care units.

PMID- 19394228
TI  - On the inhibition of HIV-1 protease by hydrazino-ureas displaying the N-->C=O
      interaction.
AB  - To create novel HIV-1 protease (HIV PR) inhibitors, we have extended our
      investigations of the N-->C=O interaction as a moiety that reproduces
      electrostatic properties of the transition state of peptidolysis. Consequently,
      we prepared a series of compounds with an unusual hydrazino-urea core. In polar
      protic media, these adopt solely a cyclic constitution displaying the interaction
      on one side of the molecule while offering a urea moiety on the opposite side
      meant to hydrogen-bond with the enzyme flaps. Each inhibitor candidate was
      obtained via a key series of three synthetic steps employing carbonyl-di
      imidazole (CDI). It was thus possible to efficiently fuse two independent
      building blocks, a hydrazine and a protected aminoaldehyde in a convergent
      manner. NMR and UV analysis proved that all compounds, when dissolved in polar
      protic media, existed exclusively in the cyclic constitution exhibiting the N-
      >C=O interaction. In total, five inhibitor candidates were tested with HIV PR for
      their potency. The one carrying the least bulk in peripheral substituents showed
      the highest activity. Its very low molecular weight (365 g/mol) holds great
      promise for future improvements in affinity without violating Lipinski's rule of
      remaining within the limit of 500 g/mol.

PMID- 19394225
TI  - Chromatin: the interface between extrinsic cues and the epigenetic regulation of
      muscle regeneration.
AB  - Muscle regeneration provides a paradigm by which to study how extrinsic signals
      coordinate gene expression in somatic stem cells (satellite cells) by directing
      the genome distribution of chromatin-modifying complexes. Understanding the
      signal-dependent control of the epigenetic events underlying the transition of
      muscle stem cells through sequential regeneration stages holds the promise to
      reveal new targets for selective interventions toward repairing diseased muscles.
      This review describes the latest findings on how regeneration cues are integrated
      at the chromatin level to build the transcription network that regulates
      progression of endogenous muscle progenitors throughout the myogenic program. In
      particular, we describe how specific epigenetic signatures can confer
      responsiveness to extrinsic cues on discrete regions of the muscle stem cell
      genome.

PMID- 19394229
TI  - 2,4(5)-diarylimidazoles as inhibitors of hNaV1.2 sodium channels: pharmacological
      evaluation and structure-property relationships.
AB  - Sodium (Na) channels continue to represent an important target for the
      development of novel anticonvulsants. We have synthesized and evaluated a series
      of 2,4(5)-diarylimidazoles for inhibition of the human neuronal Na(V)1.2 Na
      channel isoform. Starting with the unsubstituted lead compound previously
      published 3, SAR studies were performed introducing substituents with different
      physico-chemical properties. Lipophilicity (log D(7.4)) and basicity (pK(a)) of
      the compounds were measured and submitted for QSPR investigations. Some of the
      active compounds described had IC(50) values that were considerably lower than
      our lead compound. In particular, the m-CF(3) disubstituted 22 was the most
      active compound, inhibiting hNa(V)1.2 currents within the nanomolar concentration
      range (IC(50)=200 nM). In comparison, lamotrigine and phenytoin, two clinically
      used anticonvulsant drugs known to inhibit Na channels, had IC(50)'s values that
      were greater than 100 microM.

PMID- 19394230
TI  - 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl
      derivatives as a new class of potent inhibitors of Interleukin-8-induced
      neutrophil chemotaxis.
AB  - A series of 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5
      carbonyl derivatives was synthesized. The compounds demonstrated to be novel,
      potent and selective inhibitors of Interleukin-8-induced human neutrophil
      chemotaxis. A SAR study was performed by varying the carbonyl function at
      position 5 and the chain linked to the amino group at position 6 of the scaffold.
      All the compounds of the series displayed inhibitory activity at nano- or
      picomolar concentrations against Interleukin-8-driven migration and no activity
      against fMLP- and C5a-induced chemotaxis. The binding tests of selected compounds
      on CXCR1 and CXCR2 receptors were negative. The most potent derivative showed in
      vivo efficacy in a mouse model of Zymosan-induced peritonitis.

PMID- 19394232
TI  - Studies on novel 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones as
      potential TACE inhibitors: design, synthesis, molecular modeling, and preliminary
      biological evaluation.
AB  - Compounds belonging to the class of 2-imidazolidinones and tetrahydropyrimidin
      2(1H)-ones were synthesized and evaluated for their TACE inhibitory activity.
      Most of the compounds showed very good TACE inhibitory activity. Docking study
      clearly indicates importance of the P1' group of the inhibitor for the TACE
      inhibitory activity. This work proves that these two classes of molecules could
      be used as potential leads for the development of TACE inhibitors.

PMID- 19394231
TI  - Steroidal bivalent ligands for the estrogen receptor: design, synthesis,
      characterization and binding affinities.
AB  - Steroidal bivalent ligands for the estrogen receptor (ER) were designed using
      crystal structures of ERalpha dimers as a template. The syntheses of several
      17alpha-ethynylestradiol-based bivalent ligands with varying linker compositions
      and lengths are described. The binding affinities of these bivalent ligands for
      ERalpha and ERbeta were determined. In the two series of bivalent ligands that we
      synthesized, there is a clear correlation between linker length and binding
      affinity, both of which reach a maximum at the same tether length. Further
      studies are underway to explore aspects of bivalent ligand and control compound
      binding to the ERs and their effects on ER dimer formation; these results will be
      reported in a subsequent publication.

PMID- 19394233
TI  - First description of B chromosomes in the family Auchenipteridae,
      Parauchenipterus galeatus (Siluriformes) of the Sao Francisco River basin (MG,
      Brazil).
AB  - B chromosomes are considered additional and non-essential; they likely originate
      from A chromosomes and follow a distinct evolution. In fish, approximately half
      of the Neotropical species with B chromosomes are Characiformes and 35% are
      Siluriformes. There has been no report of B chromosomes in Auchenipteridae until
      this moment. B chromosomes found in a population of Parauchenipterus galeatus
      from the Sao Francisco River basin in the state of Minas Gerais (Brazil) were
      small, metacentric, totally heterochromatic and exhibited intra-individual and
      inter-individual variation. The diploid number was 58 chromosomes (22
      metacentric, 16 submetacentric, 12 subtelocentric and 8 acrocentric). The
      nucleolar organizing regions were simple and the heterochromatin intercalated in
      the ribosomal sites, characterized by CMA(3) and DAPI fluorochromes, was of a GC
      rich constitution. The 5S rDNA genes were located in an intercalary position in
      only one chromosome pair. An hypothesis about the origin of the B chromosomes in
      P. galeatus and a review on B chromosomes in catfish are also presented in this
      study.

PMID- 19394234
TI  - Cytogenetics of four Omophoita species (Coleoptera, Chrysomelidae, Alticinae): a
      comparative analysis using mitotic and meiotic cells submitted to the standard
      staining and C-banding technique.
AB  - Omophoita belongs to the tribe Oedionychini and is endemic from Neotropical
      region. The species of the tribe Oedionychini have revealed certain singular
      chromosomal features, such as sex chromosomes with extremely large size,
      asynapsis, and synthelic or amphithelic orientation during meiosis. Additionally,
      some species also showed post-reductional segregation of the gigantic sex
      chromosomes in meiotic division. The purpose of this work was to characterize
      cytogenetically four Omophoita species (O. magniguttis, O. octoguttata, O.
      personata, and O. sexnotata) in relation to their diploid number, chromosomal
      morphology, type of sex chromosome system, and constitutive heterochromatin
      pattern in mitotic and meiotic cells, and compare the obtained data with those of
      related species to establish the mechanism involved in the chromosomal
      differentiation of these species during the evolutionary process. The diploid
      number, 2n=22=20+X+y, and meiotic formulae, 10II+X+y, observed in these species
      were similar to those of the same genus and other species related. The autosomal
      morphology was acrocentric in O. magniguttis and O. octoguttata, metacentric in
      O. personata, and predominantly metacentric in O. sexnotata. In all these
      species, the sex chromosomes were metacentric. The secondary constriction
      occurred in pair 6 and X chromosome of O. personata, and in pair 6 and y
      chromosome of O. sexnotata. The constitutive heterochromatin was pericentromeric
      in O. magniguttis and centromeric in O. sexnotata, with the exception of the
      mitotic sex chromosomes of O. sexnotata, in which centromeric C band was lacking.
      Additional C bands in the sex chromosomes of O. magniguttis and certain autosomes
      and sex chromosomes of O. sexnotata were observed. Collochores were indirectly
      identified in the spermatocytes of O. octoguttata, O. personata, and O.
      sexnotata. The main mechanisms involved in the karyotype evolution of these
      species were discussed.

PMID- 19394236
TI  - Transmission electron microscopy of Ca oxide nano- and microcrystals in alpha
      tricalcium phosphate prepared by sintering of beta-tricalcium phosphate.
AB  - Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used to
      study the porous and non-porous alpha-tricalcium phosphate (alpha-Ca3(PO4)2,
      alpha-TCP) prepared through a sintering procedure at 1200-1400 degrees C of beta
      tricalcium phosphate (beta-Ca3(PO4)2, beta-TCP). The interpretation of
      experimental and calculated X-ray and electron diffraction patterns showed that
      the final product at 1400 degrees C was primarily alpha-TCP but roughly 3.0-8.0
      wt.% of the starting beta-TCP phase and up to 8.0 wt.% of CaO were in the final
      product. TEM images and electron diffraction patterns showed that the CaO phase-
      formed by decomposition of TCP--exists as micron-sized areas of various oriented
      nanocrystals embedded into the bulk alpha-TCP material and also as self-standing
      spherulite particles of a few microns in size. Surprisingly, formation of CaO
      from TCP decomposition occurred at temperatures below those predicted from the
      phase diagram of the CaO-P2O5 system.

PMID- 19394235
TI  - Collagen fibers evaluation after rhBMP-2 insertion in critical-sized defects.
AB  - The objective of this investigation was to assess the quantity of collagen fibers
      with different dosages of recombinant human bone morphogenetic protein, type 2
      (rhBMP-2) associated with two different carriers, monoolein and poloxamer gels,
      in critical bone defects created in the calvaria of Wistar rats. Forty male adult
      Wistar rats were divided into eight groups of 5 animals each-group I: critical
      bone defect with application of 1 microg of rhBMP-2 combined with monoolein gel;
      group II: 3 microg of rhBMP-2 combined with monoolein gel; group III: 7 microg of
      rhBMP-2 combined with monoolein gel; group IV: 1 microg of rhBMP-2 combined with
      poloxamer gel; group V: 3 microg of rhBMP-2 combined with poloxamer gel; group
      VI: 7 microg of rhBMP-2 combined with poloxamer gel; group VII: monoolein gel
      only and group VIII: poloxamer gel only. A critical-sized defect of 6mm diameter
      was produced in the left parietal bone using a surgical round bur and a high
      speed micromotor. The bone defects were filled according to the group that
      animals belonged and after two weeks the rats were perfused and their calvarial
      bones were removed for histological processing, and collagen fibers
      quantification. Differences among the eight groups were statistically analyzed by
      Anova and Bonferroni test (p<0.05). The results did not show statistical
      difference between the groups, in exception, between the comparisons II and III.
      According to the experimental methodology used in this research, it was observed,
      in a general way, a qualitative inverse relationship between collagen fibers
      presence and rhBMP-2 quantity inserted in the critical bone defect, associated or
      not to a material carrier.

PMID- 19394237
TI  - Increase of the beam intensity for BNCT by changing the core configuration at
      THOR.
AB  - In this article, we will consider several core configurations and run the core
      calculation with MCNP to obtain the neutrons distribution at THOR. The thermal
      neutron flux inside the vertical tubes (VT-B-VT-E) and the fast neutron flux in
      the first row facing to the boron neutron capture therapy (BNCT) facility (I3-I5)
      were tallied for indication. Based on these simulation results, the fuel elements
      were rearranged during the annual repair period in 2007. The epithermal neutron
      flux at the center of BNCT beam exit in air was measured again, and the results
      showed that the beam intensity increased by 50%. Comparing the neutron
      intensities both in reactor core and at the BNCT beam exit for several core
      configurations, the results show that the BNCT beam intensity can be increased
      without decreasing the neutron intensity in core.

PMID- 19394238
TI  - Cost analysis of radiotherapy, carbon ion therapy, proton therapy and BNCT in
      Japan.
AB  - The purpose of this study was to estimate the financial costs to start BNCT as a
      clinical treatment in a hospital. To evaluate more accurate data on the precise
      costs of BNCT, we analyzed the costs of conventional radiotherapy, carbon ion and
      proton therapy and compare them to BNCT. An aggregate cost calculation of
      accelerator, buildings, equipments and staff requirements was performed.

PMID- 19394239
TI  - Preliminary liver dose estimation in the new facility for biomedical applications
      at the RA-3 reactor.
AB  - As a part of the project concerning the irradiation of a section of the human
      liver left lobe, a preliminary estimation of the expected dose was performed. To
      obtain proper input values for the calculation, neutron flux and gamma dose rate
      characterization were carried out using adequate portions of cow or pig liver
      covered with demineralized water simulating the preservation solution.
      Irradiations were done inside a container specially designed to fulfill
      temperature preservation of the organ and a reproducible irradiation position
      (which will be of importance for future planification purposes). Implantable
      rhodium based self-powered neutron detectors were developed to obtain neutron
      flux profiles both external and internal. Implantation of SPND was done along the
      central longitudinal axis of the samples, where lowest flux is expected. Gamma
      dose rate was obtained using a neutron shielded graphite ionization chamber moved
      along external surfaces of the samples. The internal neutron profile resulted
      uniform enough to allow for a single and static irradiation of the liver. For
      dose estimation, irradiation condition was set in order to obtain a maximum of 15
      Gy-eq in healthy tissue. Additionally, literature reported boron concentrations
      of 47 ppm in tumor and 8 ppm in healthy tissue and a more conservative
      relationship (30/10 ppm) were used. To make a conservative estimation of the dose
      the following considerations were done: i). Minimum measured neutron flux inside
      the sample (approximately 5 x 10(9) n cm-2 s-1) was considered to calculate dose
      in tumor. (ii). Maximum measured neutron flux (considering both internal as
      external profiles) was used to calculate dose in healthy tissue (approximately
      8.7 x 10(9) n cm-2 s-1). (iii). Maximum measured gamma dose rate (approximately
      13.5 Gy h-1) was considered for both tumor and healthy tissue. Tumor tissue dose
      was approximately 69 Gy-eq for 47 ppm of (10)B and approximately 42 Gy-eq for 30
      ppm, for a maximum dose of 15 Gy-eq in healthy tissue. As can be seen from these
      results, even for the most conservative case, minimum tumor dose will be
      acceptable from the treatment point of view, which shows that the irradiation
      conditions at this facility have quite good characteristics for the proposed
      irradiation.

PMID- 19394240
TI  - Survival benefit of boron neutron capture therapy for recurrent malignant
      gliomas.
AB  - We have applied boron neutron capture therapy (BNCT) to malignant brain tumors.
      Here we evaluated the survival benefit of BNCT for recurrent malignant glioma
      (MG). Since 2002, we have treated 22 cases of recurrent MG with BNCT. Survival
      time was analyzed with special reference to recursive partitioning analysis (RPA)
      classification, by Carson et al. Median survival times (MSTs) after BNCT for all
      patients and for glioblastoma as on-study histology at recurrence was 10.8 months
      (n=22; 95% CI, 7.3-12.8 months) and 9.6 months (n=19; 95% CI, 6.9-11.4 months),
      respectively. In our study, MST for the high-risk RPA classes was 9.1 months
      (n=11; 95% CI, 4.4-11.0 months). By contrast, the original journal data showed
      that the MST of the same RPA classes was 4.4 months (n=129; 95% CI, 3.6-5.4
      months). BNCT showed a survival benefit for recurrent MG, especially in the high
      risk group.

PMID- 19394241
TI  - Monte Carlo modelling of the influence of boron microdistribution on BNCT
      microdosimetry.
AB  - The ion transport Monte Carlo code SRIM has been used to calculate single event
      lineal energy spectra for the products of the boron-neutron capture reaction in a
      water-based medium. The event spectra have been benchmarked against spectra
      measured with a boron-loaded tissue-equivalent proportional counter (TEPC).
      Agreement is excellent and supports the use of Monte Carlo methods in
      understanding the influence of boron delivery on the effectiveness of boron
      neutron capture therapy (BNCT).

PMID- 19394242
TI  - Neutron flux mapping inside a cubic and a head PMMA phantom using indirect
      neutron radiography.
AB  - This study aims to measure the two-dimensional (2D) neutron spatial distribution
      inside a cubic and a head PMMA phantom for the purpose of further comparison with
      the treatment planning. The measurements were made by using the indirect neutron
      radiography (INR), which utilized a thin copper foil and the imaging plate. The
      developed image provides satisfactory spatial resolution and very low statistical
      error (< 1%). As to the time cost, the whole procedure normally takes less than 3
      h. The result shows that the indirect neutron radiography can be a quick and
      reliable method to provide a 2D neutron spatial distribution inside a phantom.

PMID- 19394243
TI  - Toward prompt gamma spectrometry for monitoring boron distributions during extra
      corporal treatment of liver metastases by boron neutron capture therapy: a Monte
      Carlo simulation study.
AB  - A Monte Carlo calculation was carried out for boron neutron capture therapy
      (BNCT) of extra corporal liver phantom. The present paper describes the basis for
      a subsequent clinical application of the prompt gamma spectroscopy set-up aimed
      at in vivo monitoring of boron distribution. MCNP code was used first to validate
      the homogeneity in thermal neutron field in the liver phantom and simulate the
      gamma ray detection system (collimator and detector) in the treatment room. The
      gamma ray of 478 keV emitted by boron in small specific region can be detected
      and a mathematical formalism was used for the tomography image reconstruction.

PMID- 19394244
TI  - Molecular cloning and biochemical characterization of alpha- and beta-tubulin
      from potato plants (Solanum tuberosum L.).
AB  - Few studies have investigated microtubules from plants that host pathogenic
      fungi. Considerable efforts are underway to find an antimitotic agent against
      plant pathogens like Phytophthora infestans. However, screening the effects of
      antifungal agents on plant tubulin in vivo or using purified native microtubule
      in vitro is a time consuming process. A recombinant, correctly folded,
      microtubule-like structure forming tubulin could accelerate research in this
      area. In this study, we cloned full length cDNAs isolated from potato leaves
      using reverse-transcribed polymerase chain reaction (RT-PCR). Solanum tuberosum
      (Stub) alpha-tubulin and beta-tubulin were predicted to encode 449 and 451 amino
      acid long proteins with molecular masses of 57 kDa and 60 kDa, respectively.
      Average yields of alpha- and beta-tubulin were 2.0-3.5 mg l(-1) and 1.3-3.0 mg l(
      1) of culture, respectively. The amino acids, His6, Glu198, and Phe170 involved
      in benomyl sensitivity were conserved in Stub tubulin. The dimerization of
      tubulin monomers was confirmed by western blot analysis. When combined under
      appropriate conditions, these recombinant alpha- and beta-tubulins were capable
      of polymerizing into microtubules. Accessibility of cysteine residues of tubulin
      revealed that important ligand binding sites were folded correctly. This
      recombinant tubulin could serve as a control of phytotoxicity of selected
      antimitotic fungicide compounds during in vitro screening experiments.

PMID- 19394245
TI  - Abrupt rupture of an aortic arch aneurysm into the pulmonary artery.
AB  - We report an extremely rare case of pulmonary artery dissection caused by an
      abrupt rupture of an aortic arch aneurysm into the pulmonary artery. An
      asymptomatic 80-year-old man was admitted to our hospital for elective surgical
      repair of aortic arch aneurysm. After admission, sudden onset of hoarseness and
      dyspnea developed. Echocardiography demonstrated an intimal flap in the pulmonary
      artery and abnormal shunt flow from aortic arch aneurysm into the pulmonary
      artery. At surgery, the pulmonary artery dissection involved the main pulmonary
      artery and both major branches. Total arch replacement and pulmonary artery
      reconstruction were successfully performed.

PMID- 19394246
TI  - The use of FTIR microscopy for the evaluation of anti-bacterial agents activity.
AB  - FTIR spectroscopy has been used by chemists as a powerful tool to characterize
      inorganic and organic compounds. In this study we examined the potential of FTIR
      microspectroscopy for early evaluation of the efficiency of anti-bacterial
      therapy. For this purpose, the effect of caffeic acid phenethyl ester (CAPE) and
      ampicillin on the development of bacterial infection in cell culture was
      examined. CAPE is one of the most active components of propolis which is a
      natural honeybee product with a potent anti-bacterial activity. Our results show
      early (2h post-treatment), unique and significant spectral indicators for
      successful treatment with CAPE although some of these biomarkers showed different
      trends in Gram (-) compared with Gram (+) bacteria. For instance, the intensity
      of bands at 682 and 1316 cm(-1) decreases in all examined Gram (-) bacterial
      strains while significantly increases in all examined Gram (+) bacterial strains.
      On the other hand, both Gram (+) and Gram (-) bacteria treated with ampicillin
      did not show any spectral differences compared with the control untreated
      bacteria. It seems that FTIR spectroscopy can be used as an effective tool for an
      early evaluation of the efficiency of the anti-bacterial effect of CAPE and
      probably other used drugs.

PMID- 19394248
TI  - Factors regulating circulating vascular endothelial growth factor (VEGF):
      association with bone mineral density (BMD) in post-menopausal osteoporosis.
AB  - Vascular endothelial growth factor (VEGF) plays an important role in bone health.
      We investigated the factors which influence circulating VEGF and their
      association with bone mineral density (BMD). Two hundred and fifty two post
      menopausal women aged 64.5 [9.2] years were studied. BMD was determined at the
      lumbar spine (LS), femoral neck (FN) and total hip (TH). Serum oestradiol and
      VEGF were measured. Subjects were genotyped for two polymorphic variants in the
      5' untranslated region of the VEGF gene; G(634)C and C(936)T. Positive
      correlations were seen between circulating VEGF and BMI (r=0.2, p<0.02) and
      oestradiol (r=0.25, p<0.001). Following multi-linear regression analysis, serum
      VEGF was associated with the G(634) polymorphism (p=0.08) and dietary calcium
      intake (p=0.02). The association with calcium intake may be mediated by PTH as
      suggested by the in vitro studies. Following correction for confounders, there
      was no association between circulating VEGF and BMD at any site. Both VEGF
      polymorphisms were significant predictors of LS BMD G(634)C: p=0.017 and C(936)T:
      p=0.05. Circulating VEGF may be influenced by genetic, environmental and
      endocrine factors. Polymorphic variants in the VEGF gene are associated with
      spine BMD. Further larger studies are needed.

PMID- 19394247
TI  - Hsps and aging.
AB  - Heat-shock proteins (Hsps) are increasingly being implicated in aging phenotypes
      and control of life span across species. They are targets of the conserved heat
      shock factor and insulin/IGF1-like signaling pathways that affect life span and
      aging phenotypes. Hsps are expressed in tissue-specific and disease-specific
      patterns during aging, and their level of expression and induction by stress
      correlates with and, in some instances, predicts life span. In model organisms,
      Hsps have been shown to increase life span and ameliorate aging-associated
      proteotoxicity. Finally, Hsps have emerged as key components in regulating aging
      related cellular phenotypes, including cell senescence, apoptosis and cancer. The
      Hsps, therefore, provide a metric of individual stress and aging and are
      potential targets for interventions in aging and aging-related diseases.

PMID- 19394249
TI  - Balancing clinical service and education in the radiology residency.
AB  - RATIONALE AND OBJECTIVES: Among the various medical disciplines, the radiology
      residency faces unique challenges when balancing clinical service and education,
      which have not been explored in the literature. MATERIALS AND METHODS: The
      authors present a summary of material generated during collaborative sessions at
      the 56th Annual Meeting of the Association of University Radiologists in Seattle,
      Washington, in March 2008, including strategies on maintaining an appropriate
      emphasis on education in the face of increasing service obligations, with a
      review of the pertinent literature. RESULTS: Although the topic of service and
      education has been explored in the medical and surgical literature, little has
      been published in the radiology literature. The portability of radiology and the
      relative lack of patient contact can lead to the redistribution of residents as a
      matter of convenience to fill service gaps, often at the expense of the
      educational goals of training programs. Residents and faculty members alike must
      take part in both service and educational obligations without compromising
      patient care. Physician extenders, call schedule optimization, and other
      strategies and resources can help ensure that a proper balance is maintained.
      CONCLUSION: The radiology residency presents unique challenges to the service and
      education balance. The authors highlight several strategies to address these
      challenges.

PMID- 19394250
TI  - Glucocerebrosidase gene mutations in black South Africans with Gaucher disease.
AB  - Gaucher disease (GD) is caused by mutations in the glucocerebrocidase gene (GBA)
      and presents with variable severity. Type 1 is characterized by the lack of
      neurological symptoms in childhood, whereas types 2 and 3 are early onset
      neuronopathic forms and result in premature death. Only type 1 GD has been
      reported in black South Africans and the cases are clinically severe. In this
      study both GBA mutations were identified in 18/19 black GD patients. Two
      mutations accounted for 2/3 of all observed disease causing alleles: p.T36del
      (c.222-224delTAC) (17/38 alleles) and RecNcil (8/38 alleles). Three novel
      variants were identified and assessed as being likely pathogenic mutations:
      c.413delC, W357C and D405V. Haplotype analysis supported a single origin for the
      p.T36del mutation in black South Africans on a haplotype background that is rare
      in the present population. We hypothesise that the p.T36del results in
      intracellular mislocalisation of the protein, but confirmation of the altered
      function of this allele awaits functional studies. A diagnostic test for GD has
      been implemented for black South Africans.

PMID- 19394251
TI  - Serum transferrin receptors: Distribution and diagnostic performance in pre
      school children.
AB  - Soluble transferrin receptors have gained interest in the field of diagnosing
      anemias. Reference ranges differ according to the method used for the
      quantification of sTfR. We aim to explore the distributional properties and
      diagnostic performance of sTfR in pre-school healthy children as well as in
      children with beta-thalassemia carriers, iron deficiency with normal
      hematological phenotype (ID) and iron deficiency anemia (IDA). Circulating sTfR
      as well as biochemical and hematological indices were determined in 521 pre
      school children and four groups (normal children, beta-thalassemia traits, ID and
      IDA) were formed. Diagnostic performance and distribution of sTfR according to
      age and in relation to several parameters were evaluated in every group. Three
      hundred eighty one children (261 normal, 60 beta-thalassemia traits, 44 ID and 16
      IDA) aged 1-6 years were included. We found that distribution of sTfR differed
      significantly among the four groups (Kruskal Wallis p<0.001) with children in the
      normal group exhibiting lower concentrations compared to all other. A negative
      correlation between sTfR and age occurred in the normal (beta=-0.12, p<0.001) and
      the ID groups (beta=-0.13, p=0.035). In the beta-thal and IDA groups sTfR is
      correlated to HbA(2) (beta=0.34, p=0.001) and ferritin (Spearman's rho=-0.6,
      p=0.014) respectively. An area under the curve equal to 0.63 was achieved by sTfR
      in distinguishing between normal and ID children. Sensitivity and specificity
      were 70.5% and 50% respectively at a cut-off of 2.5 mg/l. Levels of sTfR are
      negatively correlated to age in pre-school children while dyserythropoietic
      procedures like beta-thal, ID, and IDA significantly affect them. These findings
      indicated that the accuracy of sTfR in diagnosing ID from normal children is
      limited. Standardization will allow the use of formulas that combine sTfR and
      ferritin which are of greater diagnostic value than sTfR alone.

PMID- 19394252
TI  - The REM sleep behavior disorder odyssey.

PMID- 19394253
TI  - Prevalence and diagnosis of Babesia and Theileria infections in horses in Italy:
      a preliminary study.
AB  - Babesia caballi and Theileria equi are the causative agents of equine
      piroplasmosis. In this preliminary epidemiological study, 412 horses reared in
      central and northern Italy were sampled and three diagnostic methods compared,
      namely, the microscopy, the indirect fluorescent antibody test (IFAT) and a PCR.
      Possible risk factors (such as area, season, breed, activity, sex, age, and
      grazing) associated with serological positivity were evaluated. A seroprevalence
      of 68.4% was found: 12.4% of the animals had anti-T. equi antibodies, 17.9% anti
      B. caballi antibodies and 38.1% had antibodies against both species. Of the
      seropositive samples, 3.1% and 9.4% were positive to microscopy and PCR,
      respectively; 31.5% of the horses were IFAT-negative but 1.4% and 2.4% of the
      corresponding blood samples were positive to microscopy and PCR, respectively.
      Molecular techniques revealed that the species present were closely related to T.
      equi, Theileria sergenti, Theileria buffeli and the Babesia microti-like
      piroplasm provisionally named Theileria annae. Grazing was found to be a
      pronounced risk factor for equine piroplasmosis.

PMID- 19394254
TI  - QSAR analysis for quinoxaline-2-carboxylate 1,4-di-N-oxides as anti-mycobacterial
      agents.
AB  - In a continuing effort of our research group to identify new active compounds
      against Mycobacterium tuberculosis, we resort to the quantitative structure
      activity relationships (QSARs) theory. For this purpose, we employ certain
      parameters of potency, cytotoxicity and selectivity as given by the Tuberculosis
      Antimicrobial Acquisition & Coordinating Facility (TAACF) program. The molecular
      structure of 43 quinoxaline-2-carboxylate 1,4-di-N-oxide derivatives is
      appropriately represented by 1497 DRAGON type of theoretical descriptors, and the
      best linear regression models established in this work are demonstrated to result
      predictive. The application of the QSAR equations developed now serves as a
      rational guide for the proposal of new candidate structures that still do not
      have experimentally assigned biological data.

PMID- 19394255
TI  - Modelling beta-1,3-exoglucanase-saccharide interactions: structure of the enzyme
      substrate complex and enzyme binding to the cell wall.
AB  - Glycoside hydrolases are a class of enzymes that break/form the bond between
      sugar monomers (monosaccharides). Candida albicans's beta-1,3-exoglucanase (Exg),
      a family 5 glycosidase, belongs to this class of enzymes. This small protein is
      an ideal computational model for its family of enzymes and was used here to
      create several enzyme-substrate models starting from a crystallographic glucanase
      inhibitor structure. A series of enzyme-substrate complexes were generated using
      molecular docking, ranging from Exg-glucose (Exg-1Glc) to Exg-laminarihexaose
      (Exg-6Glc). Structure optimizations followed by molecular dynamics provided a
      picture of the way the enzyme and substrates interact. Molecular dynamics was
      conducted for each complex to assess the flexibility of the substrate, of the
      enzyme as a whole, and of enzyme-substrate interactions. The enzyme overall
      conformation was found to be quite rigid, although most enzyme residues increase
      mobility upon substrate binding. However, two surface loops stand out by having
      large fluctuations and becoming less flexible when the substrates were bound.
      These data point to a possible biological role for the mentioned loops,
      corresponding to amino acids 36-47 and 101-106. We propose that these loops could
      bind the enzyme to a glucan chain in the cell wall. The polysaccharide and enzyme
      structures have very complementary shapes and form numerous interactions; so it
      appears likely that the flexible loops connect the enzyme to the cell wall and
      allow it to navigate the wall to shape glucan structure.

PMID- 19394256
TI  - Deficiency in N-acetylgalactosamine-6-sulfate sulfatase results in collagen
      perturbations in cartilage of Morquio syndrome A patients.
AB  - AIM: To investigate extracellular matrix (ECM) characteristics of cortical bone
      and articular cartilage of patients with Morquio syndrome A, a lysosomal storage
      disease caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase.
      PATIENTS AND METHODS: Cartilage, bone, and fibroblasts from 2 unrelated patients
      with Morquio syndrome were used. Histological analysis on bone and cartilage was
      carried out by means of light and electron microscopy. Lysyl hydroxylation and
      cross-linking of collagen present in bone, cartilage, and fibroblast cultures was
      determined by reverse-phase high performance liquid chromatography. RESULTS: No
      histological or biochemical differences were seen in cortical bone; furthermore,
      no differences were seen in the amount and modification of collagen deposited by
      fibroblasts. Articular cartilage showed major differences: collagen fibrils show
      a wider range of fibril diameter, the fibrils are in mean thicker, the lysyl
      hydroxylation level of the triple helix is strongly decreased, the total amount
      of pyridinolines is in the lower ranges, and the ratio hydroxylysylpyridinoline
      to lysylpyridinoline is decreased. Changes were also observed with respect to the
      arrangement of proteoglycans in the extracellular matrix surrounding the
      chondrocytes. CONCLUSION: The collagen of bone and the collagen deposited by
      fibroblasts is normal, whereas the ECM of cartilage in Morquio syndrome A
      patients is affected. Thus, deficiency in N-acetylgalactosamine-6-sulfate
      sulfatase has an impact on the phenotypic properties of chondrocytes, resulting
      in the formation of cartilage that is more prone to degeneration, being an
      explanation for the occurrence of osteoarthritis in Morquio syndrome A patients
      at early age.

PMID- 19394257
TI  - Genotype-predicted tetrahydrobiopterin (BH4)-responsiveness and molecular
      genetics in Croatian patients with phenylalanine hydroxylase (PAH) deficiency.
AB  - Specific mutations in the gene encoding phenylalanine hydroxylase (PAH), located
      on chromosome 12q22-24.1, are linked to tetrahydrobiopterin (BH4; sapropterin)
      responsive phenylketonuria (PKU). Diagnosis is usually done through the newborn
      screening for PKU, followed by a BH4 loading test. So far, more than 60 mutant
      alleles, presenting with a substantial residual PAH activity (average
      approximately 47%), were identified in more than 500 patients worldwide. We
      investigated the predictive value of BH4-responsive PAH mutations in Croatian
      population. From a group of 127 PKU patients, 62 were selected (based on the
      genotype) as potentially BH4-responsive and 39 loaded with BH4 (20 mg/kg). The
      overall frequency of BH4-responsiveness (>30% blood phenylalanine reduction
      within 24 h) was 36% (14 out of 39 patients with 23 different genotypes),
      significantly less than expected. The best responders were patients with mild
      hyperphenylalaninemia (4/4; 100%), followed by mild PKU (8/9; 89%), and classical
      PKU (2/26; 8%). The most common BH(4)-responsive genotypes were p.E390G/p.R408W
      and p.P281L/p.E390G. These genotypes correspond for approximately >30% residual
      PAH activity. The p.E390G mutation was 100% associated with BH4-responsiveness,
      regardless of the second allele (p.R408W, p.P281L, p.F55Lfs, p.L249P). With
      regard to the predicted relative PAH activity of recombinantly expressed mutant
      alleles, there was a significant (p<0.002) difference between BH4-responders and
      non-responders. In a general Croatian PKU population, disease-causing mutations
      were identified on 226 alleles (99%). There were 35 different mutations: 21
      missense, 8 splice site, 3 nonsense, 2 single nucleotide deletions, and 1 in
      frame deletion. Four mutations are reported for the first time: p.E76D, p.L333P,
      p.G346E, and IVS8-2A>G. Five mutations accounted for over two-thirds of
      investigated alleles: p.L48S, p.R261Q, p.P281L, p.E390G, and p.R408W. Thus, the
      Croatian PKU population seems to be more homogenous than some other Mediterranean
      or Central European populations. This study reveals the importance of a full
      genotype for the prediction of BH4-responsiveness. In contrast to previous
      assumption and with exception of the p.E390G mutation, single allele mutations
      are not reliable for the selection of potential PKU candidates for
      pharmacological therapy with BH4.

PMID- 19394258
TI  - The first founder DGUOK mutation associated with hepatocerebral mitochondrial DNA
      depletion syndrome.
AB  - Deoxyguanosine kinase (dGK) deficiency is a frequent cause of mitochondrial DNA
      depletion associated with a hepatocerebral phenotype. In this study, we describe
      a new splice site mutation in the DGUOK gene and the clinical, radiologic, and
      genetic features of these DGUOK patients. This new DGUOK homozygous mutation
      (c.444-62C>A) was identified in three patients from two North-African
      consanguineous families with combined respiratory chain deficiencies and
      mitochondrial DNA depletion in the liver. Brain MRIs are normal in DGUOK patients
      in the literature. Interestingly, we found subtentorial abnormal myelination and
      moderate hyperintensity in the bilateral pallidi in our patients. This new
      mutation creates a cryptic splice site in intron 3 (in position -62) and is
      predicted to result in a larger protein with an in-frame insertion of 20 amino
      acids. In silico analysis of the putative impact of the insertion shows serious
      clashes in protein conformation: this insertion disrupts the alpha5 helix of the
      dGK kinase domain, rendering the protein unable to bind purine
      deoxyribonucleosides. In addition, a common haplotype that segregated with the
      disease in both families was detected by haplotype reconstruction with 10 markers
      (microsatellites and SNPs), which span 4.6 Mb of DNA covering the DGUOK locus. In
      conclusion, we report a new DGUOK splice site mutation that provide insight into
      a critical protein domain (dGK kinase domain) and the first founder mutation in a
      North-African population.

PMID- 19394259
TI  - Underreporting and underestimation of gonorrhea cases in the Taiwan National
      Gonorrhea Notifiable Disease System in the Tainan region: evaluation by a pilot
      physician-based sentinel surveillance on Neisseria gonorrhoeae infection.
AB  - OBJECTIVES: We established a pilot sentinel surveillance system for Neisseria
      gonorrhoeae infection in Tainan to evaluate underreporting in the National
      Gonorrhea Notifiable Disease System (NGNDS), and also conducted a survey to
      understand physicians' specific reasons for underreporting in the Tainan region.
      METHODS: A sentinel surveillance network consisting of six specialty clinics was
      created in Tainan City. Three hundred seventeen patients who were clinically
      diagnosed with urethritis, cervicitis, or gonorrhea were enrolled. N. gonorrhoeae
      infection was detected by urine-based PCR. A questionnaire was mailed to
      healthcare providers who potentially see patients with gonorrhea in the Tainan
      region. RESULTS: Forty-eight N. gonorrhoeae-positive subjects were identified
      from the sentinel surveillance, and none of these gonorrhea cases were notified
      to the NGNDS by their healthcare providers. During the study period, there were
      67 notified cases in the NGNDS, depicting an underestimation of at least 42% for
      this epidemic. Of the 16 healthcare providers who had seen cases in the past 3
      months, only seven (43.8%) reported that they notified the authorities and only
      23 (32%) of 71 cases were reported. 'Not collecting a specimen' and 'afraid of
      the invasion of patient privacy by the authorities' were the main reasons for the
      lack of notification. CONCLUSIONS: The underreporting of gonorrhea identified in
      this pilot is substantial. An overhaul of Taiwan's NGNDS that streamlines the
      reporting procedures and the requirement for laboratory confirmation, along with
      a continuing medical education program is warranted.

PMID- 19394260
TI  - [Induction of labor after prior cesarean delivery: A reasonable option?].

PMID- 19394261
TI  - [Screening for gestational diabetes mellitus in 2009: Let's think about it!].

PMID- 19394262
TI  - [In favour of labour induction after previous caesarean delivery].

PMID- 19394263
TI  - Novel and sensitive methods for the determination of dopamine based on the
      resonance Rayleigh scattering, second-order scattering and frequency doubling
      scattering quenching effects.
AB  - Three novel methods were designed for the determination of dopamine (DA) by means
      of the quenching effects on resonance Rayleigh scattering (RRS) and non-linear
      scattering such as second-order scattering (SOS) and frequency doubling
      scattering (FDS) intensities. In Britton-Robinson buffer medium (pH 6.02), I(3)(
      ) could react with DA to produce I(-), which resulted in the decreases of the
      RRS, SOS and FDS intensities of the ethyl violet (EV)-I(3)(-) system, and the
      decreases of scattering intensity (DeltaI) were directly proportional to the
      concentrations of DA in a certain range. The detection limit (3sigma) for DA was
      0.0195 micromol/L for the RRS method, 0.286 micromol/L for the SOS method and
      0.0985 micromol/L for the FDS method, respectively. In this work, the
      characteristics of absorption, RRS, SOS and FDS spectra of this reaction have
      been studied; the optimum reaction condition and influencing factors have been
      investigated. The methods were applied to the determination of DA in
      pharmaceutical samples with satisfactory results.

PMID- 19394264
TI  - Direct identification of non-polio enteroviruses in residual paralysis cases by
      analysis of VP1 sequences.
AB  - BACKGROUND: The 66 serotypes of human enteroviruses (EVs) are classified into
      four species A-D, based on phylogenetic relationships in multiple genome regions.
      Partial VP(1) amplification and sequence analysis are reliable methods for
      identifying non-polio enterovirus serotypes, especially in negative cell culture
      specimens from patients with residual paralysis. OBJECTIVES: In Iran during the
      years 2000-2002, there were 29 residual paralysis cases with negative cell (RD,
      HEp(2) and L(20)B) culture results. STUDY DESIGN: The genomic RNA was extracted
      from stool specimens from cases of residual paralysis and detected by
      amplification of the 5'-nontranslated region using RT-PCR with Pan-EV primers.
      Partial VP(1) amplification by semi-nested RT-PCR (snRT-PCR) and sequence
      analysis were done. RESULTS: Specimens from the 29 culture-negative cases
      contained echoviruses of six different serotypes. CONCLUSIONS: The global
      eradication of wild polioviruses is near and study of non-polio enteroviruses,
      which can cause poliomyelitis, is increasingly important to understand their
      pathogenesis. The VP(1) sequences, derived from the snRT-PCR products, allowed
      rapid molecular analysis of these non-polio strains.

PMID- 19394265
TI  - Investigations of clinical isolations of oral poliovirus vaccine strains between
      2000 and 2005 in southern Taiwan.
AB  - BACKGROUND: In Taiwan, trivalent oral poliovirus vaccine (tOPV) is in the routine
      immunization schedule, but its association with illnesses had not been examined.
      OBJECTIVES: To investigate clinical presentations and viral characteristics of
      patients with poliovirus isolates. STUDY DESIGN: Clinical data, vaccination
      records and viral sequences were retrospectively analyzed for patients from whom
      polioviruses were isolated during 2000-2005. RESULTS: OPV-like strains were the
      only pathogen identified in 208 children who were diagnosed with lower
      respiratory tract infection (24.5%), acute gastroenteritis (16.8%) or upper
      respiratory tract infection (10.6%). Timing of poliovirus isolation relative to
      the tOPV vaccination was unusual in 59 patients, including 6 before any dose and
      53 more than 10 weeks after the 3rd or later dose of tOPV. Sequence analyses of
      the VP1, 2C and 3C/D regions for 19 poliovirus isolates revealed that 4 had
      previously reported neurovirulence reversions, 1 had intertypic recombination,
      and 6 had both. No patient had neurological complications, but 3 died of
      myocarditis, including 2 with recombinant strains and 1 who never received OPV.
      CONCLUSION: This study describes the isolation of OPV-like strains from patients
      with a variety of illnesses, raising concerns about their pathogenic potential in
      an area where tOPV is routinely administered. The detection of genetic variations
      among OPV-like strains warrants continuing surveillance for these variants in
      patients with severe illnesses besides neurological complications.

PMID- 19394266
TI  - Comparison of the PapilloCheck DNA micro-array Human Papillomavirus detection
      assay with Hybrid Capture II and PCR-enzyme immunoassay using the GP5/6+ primer
      set.
AB  - BACKGROUND: Cervical screening detects precancerous cells and routine screening
      could be improved by testing for Human Papillomavirus (HPV), the virus that
      causes cervical cancer. HPV infection is common and the benefit of HPV testing
      would be identification of women who are HPV negative and at low risk of
      developing cancer. STUDY DESIGN: The aim of this study was to evaluate the
      Greiner Bio-one PapilloCheck micro-array assay (PapilloCheck) for detection of
      HPV in comparison with Hybrid Capture II (hc2) and PCR-enzyme immunoassay (PCR
      EIA) using the GP5/6+ primers. RESULTS: Samples from a cytologically defined
      population (n=878) were analysed and 187 samples also had histology information.
      Overall, 674 out of 878 samples gave a consistent result (76.8%; 95% CI 73.83
      79.52%) on all three platforms. The genotype results obtained by PapilloCheck and
      PCR-EIA were compared and 94% were consistent (95% CI 92.1-96.4%). The main
      difference was the poor Kappa agreement for detection of high risk (HR) type 35
      (Kappa=0.190) with all inconsistent results being HR positive by PCR-EIA assay
      but negative on the PapilloCheck platform. There was no statistically significant
      difference between the performance of each assay when HR HPV positive samples
      were linked with clinical result (cytology and histology grade). PapilloCheck
      detected the highest number of HR HPV infections in samples with histology
      confirmed as CIN1, CIN2 and CIN 3 (76.6%, 85% and 91.7%, respectively).
      CONCLUSIONS: Overall, PapilloCheck proved to be a sensitive, reproducible, robust
      molecular assay for HPV genotyping with the potential for high throughput of
      specimens in a clinical setting.

PMID- 19394267
TI  - The diagnostic value of vestibular-evoked myogenic potential in patients with
      vestibular schwannoma.
AB  - OBJECTIVE: This study examined the diagnostic value of the vestibular-evoked
      myogenic potential (VEMP) in comparison with the caloric test in patients with
      vestibular schwannoma (VS). METHODS: Data were retrospectively collected from 803
      consecutive patients who visited our vertigo clinic and underwent vestibular
      tests. Amongst them, 78 patients were diagnosed as having untreated unilateral
      VS. VEMP was performed using click and short-tone burst stimulation. The caloric
      test was performed using ice water. The sensitivity and specificity of each test
      were evaluated. RESULTS: Of the 78 patients with VS, 63 had abnormal VEMPs as
      well as abnormal caloric responses. Of the 725 patients without VS, 382 had
      normal VEMPs and 416 had normal caloric responses. The sensitivity and
      specificity of VEMP were 80.8% (95% CI: 72.0-89.5%) and 52.7% (95% CI: 49.1
      56.3%), respectively; those of the caloric test were 80.8% (95% CI: 72.0-89.5%)
      and 57.4% (95% CI: 53.8-61.0%), respectively. CONCLUSIONS: The sensitivity and
      specificity of VEMP and the caloric test showed no significant differences.
      SIGNIFICANCE: In patients with VS, although the specificity of VEMP was not very
      high, its sensitivity was high and comparable to that of the caloric test.

PMID- 19394268
TI  - The sensory component of tonic motor control.

PMID- 19394269
TI  - Establishing safety limits for transcranial direct current stimulation.

PMID- 19394270
TI  - Directional organization of sensorimotor oscillatory activity related to the
      electromyogram in the monkey.
AB  - OBJECTIVE: To investigate cortical control of the electromyogram (EMG). METHODS:
      We examined the directed transfer function (DTF) between the EMG and local field
      potential oscillations in the monkey sensorimotor area during both an isotonic
      muscle contraction task and the rest condition with EMG silence. DTF computation
      based on a multivariate model is suitable for analyzing the directional structure
      of a reciprocally interconnected system. RESULTS: We found that DTF between the
      cortex and EMG in the beta band is predominantly centrifugal and largest at the
      anterior bank of the central sulcus. As for the cortico-cortical DTF within the
      sensorimotor area, the effective connectivity in the beta band was reciprocal
      across the central sulcus but was dominated by a posterior-to-anterior direction,
      especially during the muscle contraction task. The asymmetry of the DTF during
      the rest condition was inconsistent across the monkeys. CONCLUSIONS: These
      findings indicate the functional relevance of field potential oscillations in the
      post- as well as pre-central gyri in generating EMG rhythmicity. SIGNIFICANCE:
      This supports the idea that information flow from the post- to pre-central gyri
      is a key element in volitional muscle contraction.

PMID- 19394271
TI  - Levels of metabolites of organophosphate pesticides, phthalates, and bisphenol A
      in pooled urine specimens from pregnant women participating in the Norwegian
      Mother and Child Cohort Study (MoBa).
AB  - Concerns about reproductive and developmental health risks of exposure to
      organophosphate (OP) pesticides, phthalates, and bisphenol A (BPA) among the
      general population are increasing. Six dialkyl phosphate (DAP) metabolites, 3,5,6
      trichloro-2-pyridinol (TCPy), BPA, and fourteen phthalate metabolites were
      measured in 10 pooled urine samples representing 110 pregnant women who
      participated in the Norwegian Mother and Child Birth Cohort (MoBa) study in 2004.
      Daily intakes were estimated from urinary data and compared with reference doses
      (RfDs) and daily tolerable intakes (TDIs). The MoBa women had a higher mean BPA
      concentration (4.50 microg/L) than the pregnant women in the Generation R Study
      (Generation R) in the Netherlands and the National Health and Nutrition
      Examination Survey (NHANES) in the United States. The mean concentration of total
      DAP metabolites (24.20 microg/L) in MoBa women was higher than that in NHANES
      women but lower than that in Generation R women. The diethyl phthalate metabolite
      mono-ethyl phthalate (MEP) was the dominant phthalate metabolite in all three
      studies, with the mean concentrations of greater than 300 microg/L. The MoBa and
      Generation R women had higher mean concentrations of mono-n-butyl phthalate
      (MnBP) and mono-isobutyl phthalate (MiBP) than the NHANES women. The estimated
      average daily intakes of BPA, chlorpyrifos/chlorpyrifos-methyl and phthalates in
      MoBa (and the other two studies) were below the RfDs and TDIs. The higher levels
      of metabolites in the MoBa participants may have been from intake via pesticide
      residues in food (organophosphates), consumption of canned food, especially
      fish/seafood (BPA), and use of personal care products (selected phthalates).

PMID- 19394272
TI  - Neuro-exocytosis: botulinum toxins as inhibitory probes and versatile
      therapeutics.
AB  - For the fundamental process of quantal neurotransmitter release, a consensus is
      being reached on the recycling pathways for transmitter-containing, small
      synaptic vesicles (SSVs), and major inroads have been made into deciphering the
      multiple steps of regulated exocytosis. These advances arose from the
      identification of approximately 80 proteins in SSVs, elucidation of the
      structures of pertinent macromolecular complexes, utilisation of different
      serotypes (A-G) of botulinum neurotoxin (BoNT) together with transgenic mice
      lacking key genes. Hence, converging evidence continues to emerge for the
      sequential formation of complexes between the three SNAREs (SNAP-25, syntaxin and
      VAMP) and their regulatory proteins (complexins, Munc18), as well as for the Ca2+
      triggering of membrane fusion/exocytosis via its sensor, synaptotagmin. Moreover,
      molecular data gained on BoNTs have been translated into Clinical Medicine with
      type A now being applied worldwide for effectively treating >100 human conditions
      due to overactivity of nerves supplying various muscles or glands. A recent
      advance is the successful engineering of a chimera from two BoNTs to acquire the
      capability of re-targeting a more active moiety to sensory neurons, with
      resultant inhibition of the release of a pain mediator. Encouragingly, this novel
      recombinant protein blocks the exocytotic response triggered by a stimulant
      (capsaicin) of nociceptive C fibres that activates their vanilloid receptors, a
      feat not possible for either parental toxin. Reaching this landmark has generated
      optimism for designing further variants of such a versatile therapeutic for
      normalising the hyper-activity of particular cell types, especially those
      underlying the many cases of chronic pain that do not respond to existing drugs.

PMID- 19394273
TI  - Mammalian neuromuscular junctions: modern tools to monitor synaptic form and
      function.
AB  - Studies of neuromuscular synaptic structure and function have, historically,
      given general insights into synaptic mechanisms, whose principles were then
      extended to most other chemical synapses in diverse nervous systems. Often, these
      insights have been acquired through rigorous application of novel tools. Here,
      two genetic approaches to the visualisation of neuromuscular form and physiology
      are highlighted: first, mice expressing spectral variants of green fluorescent
      protein in neurones, axons and motor nerve terminals, including the 'brainbow'
      mouse transgenic lines. Second, the expression of pH-sensitive indicators of
      exocytosis and endocytosis in synaptopHluorin mice has uncovered intriguing
      facets to the regulation of synaptic strength. This transgenic approach, in
      addition to facilitating achievement of the goal to define brain connectivity and
      synaptic function at a cellular level, also points to ways of appraising new
      therapeutic avenues focused on synaptic involvement in neurodegenerative
      diseases.

PMID- 19394274
TI  - Promoting learning transfer in post registration education: a collaborative
      approach.
AB  - Pre-registration nurse education in Ireland became a four year undergraduate
      honors degree programme in 2002 (Government of Ireland, 2000. The Nursing
      Education Forum Report. Dublin, Dublin Stationary Office.). Consequently, the
      Irish Government invested significant resources in post registration nursing
      education in order to align certificate and diploma trained nurses with the
      qualification levels of new graduates. However, a general concern amongst
      academic and clinical staff in the South East of Ireland was that there was
      limited impact of this initiative on practice. These concerns were addressed
      through a collaborative approach to the development and implementation of a new
      part-time post registration degree that incorporated an enquiry and practice
      based learning philosophy. The principles of learning transfer (Ford, K., 1994.
      Defining transfer of learning the meaning is in the answers. Adult Learning 5
      (4), p. 2214.) underpinned the curriculum development and implementation process
      with the goal of reducing the theory practice gap. This paper reports on all four
      stages of the curriculum development process: exploration, design, implementation
      and evaluation (Quinn, F.M., 2002. Principles and Practices of Nurse Education,
      fourth ed. Nelson Thornes, Cheltenham), and the subsequent impact of learning
      transfer on practice development. Eclectic approaches of quantitative and
      qualitative data collection techniques were utilised in the evaluation. The
      evaluation of this project to date supports our view that this practice based
      enquiry curriculum promotes the transfer of learning in the application of
      knowledge to practice, impacting both student and service development.

PMID- 19394275
TI  - Learning to learn in practice: An evaluation of a 35-day practice orientation
      programme.
AB  - The Practice Education Support Unit at Thames Valley University is committed to
      improving the quality of students' practice experience. Recent changes to the
      delivery of the Pre-Registration nursing curriculum have included the instigation
      of a 35-day practice orientation programme for students on the common foundation
      programme. The Brent and Harrow 'Student Experiences Group' developed and
      facilitated a 35-day programme for the March 2007 cohort within their learning
      community. Subsequent evaluation of the programme revealed that students were
      more positive in relation to taught elements of the programme, as opposed to self
      directed elements. These results are significant due to the requirement for
      students to develop self-direction skills in order to become competent registered
      nurses. The evaluation results did indicate the need for changes to be made to
      the subsequent development of the 35-day programme for the September 2007 cohort.
      In particular, the programme was redesigned to create a better balance between
      taught and self directed elements. A staged introduction to self-directed
      learning may promote student acceptance and confidence in this vital skill.

PMID- 19394276
TI  - Meeting the challenges in cardiovascular nursing.

PMID- 19394278
TI  - Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3
      expression in patients with Common Variable Immunodeficiency: a link to
      autoimmunity?
AB  - Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease
      characterized by defective immunoglobulin production and often associated with
      autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T
      regulatory (Treg) cells and ask whether perturbations in their frequency in
      peripheral blood could underlie the high incidence of autoimmune disorders in
      CVID patients. In this study, we report for the first time that CVID patients
      with autoimmune disease have a significantly reduced frequency of
      CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a
      decreased intensity of FOXP3 expression. Notably, although CVID patients in whom
      autoimmunity was not diagnosed had a reduced frequency of
      CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those
      in healthy controls. In conclusion, these data suggest compromised homeostasis of
      CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity,
      and may implicate Treg cells in pathological mechanisms of CVID.

PMID- 19394280
TI  - T cell large granular lymphocyte leukemia associated with rheumatoid arthritis
      and neutropenia.
AB  - T cell large granular lymphocyte leukemia (T-LGL) is a disease characterized by
      clonal expansion of cytotoxic T cells (CTLs). It generally follows an indolent
      course and is notable for an association with chronic inflammation, neutropenia
      and rheumatoid arthritis (RA). We present herein a case of a patient with
      rheumatoid arthritis (RA), neutropenia, large granular lymphocytosis, and an
      expanded clonal population of peripheral blood CD3(+)CD8(+)TCRalphabeta CTLs,
      consistent with the diagnosis of T-LGL. T-LGL is part of a spectrum of large
      granular lymphocytic (LGL) disorders, which includes the more common indolent
      variety of this disease (as illustrated by the case herein), an aggressive but
      rare form of this leukemia, natural killer (NK) cell LGL leukemia, Felty's
      syndrome (FS), and chronic large granular lymphocytosis. T-LGL appears to be a
      relatively rare disease, but the true prevalence is not known. FS occurs in less
      than 1% of patients with RA and is typically defined by the triad of destructive
      arthritis, neutropenia, and variable splenomegaly. A subset of patients with FS
      will demonstrate polyclonal expansion of LGLs, implying a relationship between
      proliferation of LGLs and the mechanisms of neutropenia. Thus, T-LGL leukemia and
      FS with LGL expansion in the setting of RA is classically distinguished by the
      clonality of the CTL population, with monoclonality in T-LGL and polyclonality in
      FS. Despite this difference, T-LGL and FS are often similar in their clinical and
      biological behavior. Both may respond to immunosuppressive therapy, and pursue a
      smoldering course typical of a chronic inflammatory disease.

PMID- 19394279
TI  - Decreased DNA methyltransferase levels contribute to abnormal gene expression in
      "senescent" CD4(+)CD28(-) T cells.
AB  - A senescent CD4(+)CD28(-) T cell subset develops with aging and in chronic
      inflammatory diseases like rheumatoid arthritis, and is implicated in plaque
      rupture and myocardial infarctions. This subset is pro-inflammatory, cytotoxic
      for endothelial cells, and aberrantly expresses genes like CD70, perforin and
      killer cell immunoglobulin-like receptor (KIR) genes. Why CD4(+)CD28(-) cells
      overexpress these genes is unclear. We found that the CD70, perforin and KIR2DL4
      promoters are demethylated in CD4(+)CD28(-) T cells, and that DNA
      methyltransferase 1 (Dnmt1) and Dnmt3a levels are decreased in this subset. siRNA
      "knockdown" of Dnmt1, but not Dnmt3a, in CD4(+)CD28(+) T cells caused similar
      demethylation and overexpression of KIR2DL4, perforin and CD70, while
      simultaneous knockdown of Dnmt1 and Dnmt3a caused greater demethylation and
      overexpression of these genes than Dnmt1 alone. We conclude that decreased Dnmt1
      and Dnmt3a cause demethylation and overexpression of these and perhaps other
      genes in CD4(+)CD28(-) cells, potentially contributing to pathologic functions by
      this subset.

PMID- 19394281
TI  - Biointeraction analysis by high-performance affinity chromatography: Kinetic
      studies of immobilized antibodies.
AB  - A system based on high-performance affinity chromatography was developed for
      characterizing the binding, elution and regeneration kinetics of immobilized
      antibodies and immunoaffinity supports. This information was provided by using a
      combination of frontal analysis, split-peak analysis and peak decay analysis to
      determine the rate constants for antibody-antigen interactions under typical
      sample application and elution conditions. This technique was tested using
      immunoaffinity supports that contained monoclonal antibodies for 2,4
      dichlorophenoxyacetic acid (2,4-D). Association equilibrium constants measured by
      frontal analysis for 2,4-D and related compounds with the immobilized antibodies
      were 1.7-12x10(6)M(-1) at pH 7.0 and 25 degrees C. Split-peak analysis gave
      association rate constants of 1.4-12x10(5)M(-1)s(-1) and calculated dissociation
      rate constants of 0.01-0.4s(-1) under the application conditions. Elution at pH
      2.5 for the analytes from the antibodies was examined by peak decay analysis and
      gave dissociation rate constants of 0.056-0.17s(-1). A comparison of frontal
      analysis results after various periods of column regeneration allowed the rate of
      antibody regeneration to be examined, with the results giving a first-order
      regeneration rate constant of 2.4x10(-4)s(-1). This combined approach and the
      information it provides should be useful in the design and optimization of
      immunoaffinity chromatography and other analytical methods that employ
      immobilized antibodies. The methods described are not limited to the particular
      analytes and antibodies employed in this study but should be useful in
      characterizing other targets, ligands and supports.

PMID- 19394282
TI  - Simultaneous determination of tryptophan and kynurenine in plasma samples of
      children patients with Kawasaki disease by high-performance liquid chromatography
      with programmed wavelength ultraviolet detection.
AB  - A simple, fast, sensitive and specific high-performance liquid chromatography
      (HPLC) method is developed for simultaneous determination of kynurenine (Kyn) and
      tryptophan (Trp) with ultraviolet (UV) detection setting programmed wavelength.
      The separation was carried out on an Agilent Hypersil ODS column (125 mm x 4.0
      mm, 5 microm) in less than 6 min and the eluate was monitored by the programmed
      wavelength detection setting at 360 nm from 0 min to 4 min for Kyn, and at 278 nm
      from 4 min to 6 min for Trp in a single run with UV detector. The linearities of
      the method were from 0.20 micromol/L to 21.2 micromol/L for Kyn and 2.25-678.0
      micromol/L for Trp, and the detection limits were 0.028 micromol/L for Kyn and
      0.053 micromol/L for Trp, respectively. Satisfactory precisions and recoveries
      were obtained by this method. The assay was employed to analyze plasma samples of
      children patients with Kawasaki disease (KD). The result showed great difference
      between Kawasaki disease and control group.

PMID- 19394283
TI  - Determination of 2,3-dimercaptosuccinic acid in mice blood and tissues by HPLC
      with fluorescence detection.
AB  - 2,3-Dimercaptosuccinic acid (DMSA) is an orally effective chelating agent for the
      treatment of heavy metal poisoning. The increasing therapeutic use of DMSA has
      stimulated the need for sensitive and selective methods for its determination in
      biological samples, as well as study on pharmacokinetics and tissue distribution.
      According to the previously reported method, an improved method was established
      for the determination of DMSA in mice blood and tissues, in which oxidized DMSA
      was reduced by the disulfide-reducing agent, dithiothreitol (DTT), and DMSA was
      converted to a highly fluorescent and stable derivative by reaction with
      monobromobimane (mBBr) in alkaline solution. Acetonitrile was used for
      deproteinization and dichloromethane was used for condensation and purification,
      which significantly shortened the amount of time used to process the sample.
      Meanwhile isocratical elution was performed and excellent separation of the DMSA
      derivative was obtained, this enabled a run finish within 20 min. The limits of
      quantitation were 0.025 microg/ml in brain and 0.1 microg/ml in blood, lung,
      heart, intestine, liver, spleen and kidney, respectively. The calibration curves
      were linear in all samples (r(2)>0.992) with a range of 0.025-1.6 microg/ml for
      brain homogenate and 0.1-6.4 microg/ml for blood and homogenates of lung, heart,
      intestine, liver, spleen and kidney, respectively. Therefore, the method is
      simple, rapid and sensitive, and it could be applicable to the studies in an
      animal model to evaluate the distribution of DMSA in blood and tissues.

PMID- 19394284
TI  - Influence of nanopatterns on endothelial cell adhesion: Enhanced cell retention
      under shear stress.
AB  - In this study, nanopatterned crosslinked films of collagen Type I were seeded
      with human microvascular endothelial cells and tested for their suitability for
      vascular tissue engineering. Since the films will be rolled into tubes with
      concentric layers of collagen, nutrient transfer through the collagen films is
      quite crucial. Molecular diffusivity through the collagen films, cell viability,
      cell proliferation and cell retention following shear stress were studied. Cells
      were seeded onto linearly nanogrooved films (groove widths of 332.5, 500 and
      650nm), with the grooves aligned in the direction of flow. The nanopatterns did
      not affect cell proliferation or initial cell alignment; however, they
      significantly affected cell retention under fluid flow. While cell retention on
      unpatterned films was 35+/-10%, it was 75+/-4% on 332.5nm patterned films and
      even higher, 91+/-5%, on 650nm patterned films. The films were found to have
      diffusion coefficients of ca. 10(-6)cm(2)s(-1) for O(2) and 4-acetaminophenol,
      which is comparable to that observed in natural tissues. This constitutes another
      positive asset of these films for consideration as a scaffold material for
      vascular tissue engineering.

PMID- 19394285
TI  - Do current standards of primary care of diabetes meet with guideline
      recommendations in Trinidad, West Indies?
AB  - AIMS: Primary care management of diabetes was examined using the Caribbean Health
      Research Council (CHRC) guidelines. METHODS: We retrospectively examined a cross
      section of 646 type 2 people with diabetics over 12 months with 1st visit between
      1997 and 2005. RESULTS: There were more women (65.8%) than men (34.2%) with age
      range between 29 and 89 years. Blood pressure and weight were evaluated in >95%
      of patients at each centre. Waist circumference and BMI were not measured at any
      time and HbA(1)c was infrequently measured (1.6-7%) over the 12 months.
      Information on family history (87.5%), smoking and alcohol (78.1%), exercise
      (21.4%), socioeconomic status (19.4%) and education (0.3%), and fasting blood
      sugar (97.2%), lipid profile (51.8%) and serum creatinine (37.9%) were assessed
      at the 1st visit. At follow-up patients were advised on treatment compliance
      (47.2%), diet (34.2%), exercise (18.5%) and rarely on home monitoring of blood
      glucose (0.3%). Peripheral sensations, pedal pulses (6%), visual acuity (3.3%),
      fundoscopy (12.1%) and ECG (3.9%) were scarcely examined at the annual visit.
      CONCLUSIONS: Current management of diabetes in primary care in Trinidad falls
      short of Caribbean guideline recommendations. The CHRC and Ministry of Health
      should jointly educate caregivers of diabetes to implement the guidelines, with
      annual audits to identify shortfalls in management.

PMID- 19394286
TI  - Assessment of the diagnostic accuracy of circulating natriuretic peptide
      concentrations to distinguish between cats with cardiac and non-cardiac causes of
      respiratory distress.
AB  - OBJECTIVES: To determine if serum natriuretic peptide (NP) concentrations could
      distinguish cardiac from non-cardiac causes of respiratory distress (RD) in cats.
      ANIMALS: Seventy-four cats from 1 university hospital were used. METHODS: Serum
      NP concentrations were measured in 41 cats with non-cardiac respiratory distress
      (RD-NC) and compared to 33 cats with RD due to congestive heart failure (RD+CHF)
      using sandwich enzyme immunoassays (ELISA). RESULTS: RD-NC cats had lower
      (P=0.0001) median NT-proANP and NT-proBNP concentrations (614 and 45 fmol/mL,
      respectively) than RD+CHF cats (1690 and 523 fmol/mL, respectively). The area
      under the curve was 0.88 and 0.96 for the receiver operating curve analysis of
      the diagnostic accuracy of NT-proANP and NT-proBNP concentrations to discriminate
      RD+CHF from RD-NC cats (P=0.036). An optimum cut-off concentration of 986 fmol/mL
      for NT-proANP and 220 fmol/mL for NT-proBNP accurately discriminated RD-NC from
      RC+CHF cats with a sensitivity of 93.8% and 93.9% and a specificity of 80.3% and
      87.8%, respectively. CONCLUSIONS: Serum NP concentrations were different in
      RD+CHF cats compared to RD-NC cats. Evaluation of circulating NP concentrations
      may be helpful in the initial approach to cats presenting with respiratory
      distress, particularly if advances in ELISA technology result in a rapid cage
      side test.

PMID- 19394287
TI  - Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to
      distinguish between congestive heart failure and non-cardiac causes of acute
      dyspnea in cats.
AB  - BACKGROUND: Circulating plasma N-terminal pro-brain natriuretic peptide (NT
      proBNP) concentration facilitates emergency diagnosis of congestive heart failure
      (CHF) in people. Its utility to discriminate between dyspneic cats with CHF vs.
      primary respiratory disease requires further assessment. Our objectives were to
      determine if NT-proBNP (1) differentiates dyspneic cats with CHF vs. primary
      respiratory disease; (2) increases with renal insufficiency; (3) correlates with
      left atrial dimension, radiographic cardiomegaly, and estimated left ventricular
      filling pressure (E/E(a)). METHODS: NT-proBNP was measured in 167 dyspneic cats
      (66 primary respiratory disease, 101 CHF) to evaluate (1) relationship with
      clinical parameters; (2) ability to distinguish CHF from primary respiratory
      disease; (3) optimal cut-off values using receiver operating characteristic (ROC)
      curve analysis. RESULTS: NT-proBNP (1) was higher (median and inter-quartile
      [25th-75th] percentile) in CHF (754 pmol/L; 437, 1035 pmol/L) vs. primary
      respiratory disease (76.5 pmol/L; 24, 180 pmol/L) cohorts (P<0.001); (2)
      positively correlated in CHF cats with increased inter-ventricular septal end
      diastolic thickness (rho=0.266; P=0.007) and LV free wall thickness (rho=0.218;
      P=0.027), but not with radiographic heart size, left atrial size, left
      ventricular dimensions, E/E(a) ratio, BUN, creatinine, or thyroxine; (3)
      distinguished dyspneic CHF cats from primary respiratory disease at 265 pmol/L
      cut-off value with 90.2% sensitivity, 87.9% specificity, 92% positive predictive
      value, and 85.3% negative predictive value (area under ROC curve, 0.94).
      CONCLUSIONS: NT-proBNP accurately discriminated CHF from respiratory disease
      causes of dyspnea.

PMID- 19394288
TI  - Targeting of mRNAs to their sites of unconventional splicing in the unfolded
      protein response.
AB  - In this issue of Molecular Cell (Yanagitani et al., 2009) and recently published
      in Nature (Aragon et al., 2009) are reports on the importance of mRNA
      localization for unconventional splicing in the unfolded protein response, but
      the two papers suggest very different mechanisms in mammals and yeast.

PMID- 19394289
TI  - The APC/C: a smorgasbord for proteolysis.
AB  - In a recent issue of Molecular Cell, Matyskiela and Morgan (2009) identify the
      sites on the APC/C that are required for activation and substrate binding,
      providing insights into how the APC/C works, with implications for the spindle
      assembly checkpoint that regulates it.

PMID- 19394290
TI  - Systems biology makes it personal.
AB  - Systems biology promises to personalize medicine via network-based biomarkers
      that predict therapeutic effectiveness. Toward this goal, Chang et al. (2009)
      recently introduced a systems-based approach to break down oncogenic signaling
      networks into modules that predict the effectiveness of pathway-specific
      therapeutics.

PMID- 19394291
TI  - Protein phosphorylation goes negative.
AB  - Analyzing global protein phosphorylation by mass spectrometry remains a
      challenging task. To this end, Old et al. (2009) recently described a strategy
      that improves the coverage of phosphorylated sites and employed it to identify B
      Raf-dependent phosphorylation sites in melanoma cells.

PMID- 19394292
TI  - Direct binding of CoREST1 to SUMO-2/3 contributes to gene-specific repression by
      the LSD1/CoREST1/HDAC complex.
AB  - Posttranslational modification of transcription factors by the small ubiquitin
      related modifier SUMO is associated with transcriptional repression, but the
      underlying mechanisms remain incompletely described. We have identified binding
      of the LSD1/CoREST1/HDAC corepressor complex to SUMO-2. Here we show that CoREST1
      binds directly and noncovalently to SUMO-2, but not SUMO-1, and CoREST1 bridges
      binding of the histone demethylase LSD1 to SUMO-2. Depletion of SUMO-2/3
      conjugates led to transcriptional derepression, reduced occupancy of CoREST1 and
      LSD1, and changes in histone methylation and acetylation at some, but not all,
      LSD1/CoREST1/HDAC target genes. We have identified a nonconsensus SUMO
      interaction motif (SIM) in CoREST1 required for SUMO-2 binding, and we show that
      mutation of the CoREST1 SIM disrupted SUMO-2 binding and transcriptional
      repression of some neuronal-specific genes in nonneuronal cells. Our results
      reveal that direct interactions between CoREST1 and SUMO-2 mediate SUMO-dependent
      changes in chromatin structure and transcription that are important for cell-type
      specific gene expression.

PMID- 19394293
TI  - An alpha motif at Tas3 C terminus mediates RITS cis spreading and promotes
      heterochromatic gene silencing.
AB  - RNA interference (RNAi) plays a pivotal role in the formation of heterochromatin
      at the fission yeast centromeres. The RNA-induced transcriptional silencing
      (RITS) complex, composed of heterochromatic small interfering RNAs (siRNAs), the
      siRNA-binding protein Ago1, the chromodomain protein Chp1, and the Ago1/Chp1
      interacting protein Tas3, provides a physical tether between the RNAi and
      heterochromatin assembly pathways. Here, we report the structural and functional
      characterization of a C-terminal Tas3 alpha-helical motif (TAM), which self
      associates into a helical polymer and is required for cis spreading of RITS in
      centromeric DNA regions. Site-directed mutations of key residues within the
      hydrophobic monomer-monomer interface disrupt Tas3-TAM polymeric self-association
      in vitro and result in loss of gene silencing, spreading of RITS, and a dramatic
      reduction in centromeric siRNAs in vivo. These results demonstrate that, in
      addition to the chromodomain of Chp1 and siRNA-loaded Ago1, Tas3 self-association
      is required for RITS spreading and efficient heterochromatic gene silencing at
      centromeric repeat regions.

PMID- 19394294
TI  - Rtr1 is a CTD phosphatase that regulates RNA polymerase II during the transition
      from serine 5 to serine 2 phosphorylation.
AB  - Messenger RNA processing is coupled to RNA polymerase II (RNAPII) transcription
      through coordinated recruitment of accessory proteins to the Rpb1 C-terminal
      domain (CTD). Dynamic changes in CTD phosphorylation during transcription
      elongation are responsible for their recruitment, with serine 5 phosphorylation
      (S5-P) occurring toward the 5' end of genes and serine 2 phosphorylation (S2-P)
      occurring toward the 3' end. The proteins responsible for regulation of the
      transition state between S5-P and S2-P CTD remain elusive. We show that a
      conserved protein of unknown function, Rtr1, localizes within coding regions,
      with maximum levels of enrichment occurring between the peaks of S5-P and S2-P
      RNAPII. Upon deletion of Rtr1, the S5-P form of RNAPII accumulates in both whole
      cell extracts and throughout coding regions; additionally, RNAPII transcription
      is decreased, and termination defects are observed. Functional characterization
      of Rtr1 reveals its role as a CTD phosphatase essential for the S5-to-S2-P
      transition.

PMID- 19394295
TI  - SR protein family members display diverse activities in the formation of nascent
      and mature mRNPs in vivo.
AB  - The SR proteins are a family of pre-mRNA splicing factors with additional roles
      in gene regulation. To investigate individual family members in vivo, we
      generated a comprehensive panel of stable cell lines expressing GFP-tagged SR
      proteins under endogenous promoter control. Recruitment of SR proteins to nascent
      FOS RNA was transcription dependent and RNase sensitive, with unique patterns of
      accumulation along the gene specified by the RNA recognition motifs (RRMs). In
      addition, all SR protein interactions with Pol II were RNA dependent, indicating
      that SR proteins are not preassembled with Pol II. SR protein interactions with
      RNA were confirmed in situ by FRET/FLIM. Interestingly, SC35-GFP also exhibited
      FRET with DNA and failed to associate with cytoplasmic mRNAs, whereas all other
      SR proteins underwent nucleocytoplasmic shuttling and associated with specific
      nuclear and cytoplasmic mRNAs. Because different constellations of SR proteins
      bound nascent, nuclear, and cytoplasmic mRNAs, mRNP remodeling must occur
      throughout an mRNA's lifetime.

PMID- 19394296
TI  - Cotranslational targeting of XBP1 protein to the membrane promotes cytoplasmic
      splicing of its own mRNA.
AB  - Endoplasmic reticulum (ER) stress triggers the cytoplasmic splicing of XBP1 mRNA
      by the transmembrane endoribonuclease IRE1alpha, resulting in activation of the
      unfolded protein response, which maintains ER homeostasis. We show that the
      unspliced XBP1 (XBP1u) mRNA is localized to the membrane, although its product is
      neither a secretory nor a membrane protein and is released to the cytosol after
      splicing. Biochemical and mutagenic analyses demonstrated that membrane
      localization of XBP1u mRNA required its in-frame translation. An insertional
      frame-shift mutation greatly diminished both membrane localization and splicing
      of the XBP1u mRNA. Furthermore, membrane localization was compromised by
      puromycin treatment and required a hydrophobic region within XBP1u. These data
      demonstrate that the nascent XBP1u polypeptide recruits its own mRNA to the
      membrane. This system serves to enhance cytoplasmic splicing and could facilitate
      a more rapid response to ER stress, and represents a unique way of
      cotranslational protein targeting coupled to mRNA maturation.

PMID- 19394297
TI  - The plasticity of a translation arrest motif yields insights into nascent
      polypeptide recognition inside the ribosome tunnel.
AB  - The recognition of a C-terminal motif in E. coli SecM
      ((150)FXXXXWIXXXXGIRAGP(166)) inside the ribosome tunnel causes translation
      arrest, but the mechanism of recognition is unknown. Whereas single mutations in
      this motif impair recognition, we demonstrate that new arrest-inducing peptides
      can be created through remodeling of the SecM C terminus. We found that R163 is
      indispensable but that flanking residues that vary in number and position play an
      important secondary role in translation arrest. The observation that individual
      SecM variants showed a distinct pattern of crosslinking to ribosomal proteins
      suggests that each peptide adopts a unique conformation inside the tunnel. Based
      on the results, we propose that translation arrest occurs when the peptide
      conformation specified by flanking residues moves R163 into a precise intratunnel
      location. Our data indicate that translation arrest results from extensive
      communication between SecM and the tunnel and help to explain the striking
      diversity of arrest-inducing peptides found throughout nature.

PMID- 19394298
TI  - Misfolded membrane proteins are specifically recognized by the transmembrane
      domain of the Hrd1p ubiquitin ligase.
AB  - Quality control pathways such as ER-associated degradation (ERAD) employ a small
      number of factors to specifically recognize a wide variety of protein substrates.
      Delineating the mechanisms of substrate selection is a principle goal in studying
      quality control. The Hrd1p ubiquitin ligase mediates ERAD of numerous misfolded
      proteins including soluble, lumenal ERAD-L and membrane-anchored ERAD-M
      substrates. We tested if the Hrd1p multispanning membrane domain was involved in
      ERAD-M specificity. In this work, we have identified site-directed membrane
      domain mutants of Hrd1p impaired only for ERAD-M and normal for ERAD-L.
      Furthermore, other Hrd1p variants were specifically deficient for degradation of
      individual ERAD-M substrates. Thus, the Hrd1p transmembrane region bears
      determinants of high specificity in the ERAD-M pathway. From in vitro and
      interaction studies, we suggest a model in which the Hrd1p membrane domain
      employs intramembrane residues to evaluate substrate misfolding, leading to
      selective ubiquitination of appropriate ERAD-M clients.

PMID- 19394299
TI  - Structural insights into formation of an active signaling complex between Rac and
      phospholipase C gamma 2.
AB  - Rho family GTPases are important cellular switches and control a number of
      physiological functions. Understanding the molecular basis of interaction of
      these GTPases with their effectors is crucial in understanding their functions in
      the cell. Here we present the crystal structure of the complex of Rac2 bound to
      the split pleckstrin homology (spPH) domain of phospholipase C-gamma(2)
      (PLCgamma(2)). Based on this structure, we illustrate distinct requirements for
      PLCgamma(2) activation by Rac and EGF and generate Rac effector mutants that
      specifically block activation of PLCgamma(2), but not the related PLCbeta(2)
      isoform. Furthermore, in addition to the complex, we report the crystal
      structures of free spPH and Rac2 bound to GDP and GTPgammaS. These structures
      illustrate a mechanism of conformational switches that accompany formation of
      signaling active complexes and highlight the role of effector binding as a common
      feature of Rac and Cdc42 interactions with a variety of effectors.

PMID- 19394300
TI  - The structure of a receptor with two associating transmembrane domains on the
      cell surface: integrin alphaIIbbeta3.
AB  - Structures of intact receptors with single-pass transmembrane domains are
      essential to understand how extracellular and cytoplasmic domains regulate
      association and signaling through transmembrane domains. A chemical and
      computational method to determine structures of the membrane regions of such
      receptors on the cell surface is developed here and validated with glycophorin A.
      An integrin heterodimer structure reveals association over most of the lengths of
      the alpha and beta transmembrane domains and shows that the principles governing
      association of hetero and homo transmembrane dimers differ. A turn at the Gly of
      the juxtamembrane GFFKR motif caps the alpha TM helix and brings the two Phe of
      GFFKR into the alpha/beta interface. A juxtamembrane Lys residue in beta also has
      an important role in the interface. The structure shows how transmembrane
      association/dissociation regulates integrin signaling. A joint ectodomain and
      membrane structure shows that substantial flexibility between the extracellular
      and TM domains is compatible with TM signaling.

PMID- 19394302
TI  - Correcting for the inner filter effect in measurements of fluorescent proteins in
      high-cell-density cultures.
AB  - Fluorescent proteins (FPs), such as green fluorescent protein (GFP) and its
      variants, are well-developed visible markers for analyzing bioprocesses. Accurate
      measurement of fluorescence emitted from FPs in whole cells is complicated by the
      inner filter effect (IFE), which is caused by intracellular light absorption and
      scattering by cell particles. The IFE causes nonlinearity between fluorescence
      intensity and fluorophore concentrations in FP-harboring cells and can
      significantly influence the accuracy of FP-based analysis, especially at high
      cell densities. A mathematical model based on detection of fluorescence intensity
      using a fluorescence spectrophotometer was developed to provide a simple
      correction for the IFE in fluorescence intensity detection in high-density
      cultures. The parameters of this model were determined in three different FP
      harboring bacterial strains to give the "real fluorescence" intensity without the
      IFE. Using these parameters, accurate analysis of FP-labeled Escherichia coli at
      high cell density in pure culture and in mixed cultures with fluorescent and
      nonfluorescent strains was easily and successfully achieved.

PMID- 19394301
TI  - Global regulators orchestrate group II intron retromobility.
AB  - Group II introns are hypothesized to share common ancestry with both nuclear
      spliceosomal introns and retrotransposons, which collectively occupy the majority
      of genome space in higher eukaryotes. These phylogenetically diverse introns are
      mobile retroelements that move through an RNA intermediate. Disruption of
      Escherichia coli genes encoding enzymes that catalyze synthesis of global
      regulators cAMP and ppGpp inhibits group II intron retromobility. These small
      molecules program genetic transitions between nutrient excess and starvation.
      Accordingly, we demonstrated that glucose depletion of wild-type cells and cAMP
      supplementation of mutants stimulated retromobility. Likewise, amino acid
      starvation, which induces the alarmone ppGpp, activated retromobility. In both
      cases, retrotransposition to ectopic sites was favored over retrohoming.
      Interestingly, these stimulatory effects are mediated at the level of the DNA
      target, rather than of expression of the retroelement. Thereby, during metabolic
      stress, cAMP and ppGpp control group II intron movement in concert with the
      cell's global genetic circuitry, stimulating genetic diversity.

PMID- 19394303
TI  - Discriminating pulmonary hypertension caused by monocrotaline toxicity from
      chronic hypoxia by near-infrared spectroscopy and multivariate methods of
      analysis.
AB  - A new method has been developed for the determination of tissue pathology caused
      by chronic hypoxia and monocrotaline toxicity. The method is based on the use of
      near-infrared (NIR) spectrophotometry to measure spectra of lung tissue from
      normal chronic hypoxia (CH) and monocrotaline (MCT) models of pulmonary
      hypertension (PH), followed by analysis using multivariate methods, that is,
      principal component analysis (PCA) and partial least squares (PLS). Synergistic
      use of NIR with the PCA/PLS method makes it possible, for the first time, not
      only to divide different lung tissue samples into their respective groups
      (normal, CH, and MCT) but also to gain insight into mechanisms of PH caused by CH
      and MCT toxicity. Specifically, MCT metabolites and other hypertensive conditions
      are known to produce subtle and minor chemical changes in the compositions of
      tissue (e.g., proteins, carbohydrates, lipids). Although these changes were
      detected by the NIR technique, they were too small to be discerned through visual
      inspection of the spectra. However, they can be accurately classified and
      properly assigned by the PCA/PLS method. The fact that different tissue types can
      be accurately divided into their corresponding groups by the NIR and PCA/PLS
      methods suggests that chemical alterations and mechanisms of pulmonary vascular
      remodeling and PH induced by MCT are different from those induced by CH.

PMID- 19394304
TI  - A protease inhibitor discovery method using fluorescence correlation spectroscopy
      with position-specific labeled protein substrates.
AB  - We developed novel substrates for protease activity evaluation by fluorescence
      correlation spectroscopy (FCS). Substrates were labeled in a position-specific
      manner with a fluorophore near the N terminus and included a C-terminal, 30 kDa,
      highly soluble protein (elongation factor Ts [EF-Ts]). The C-terminal protein
      enhanced the substrate peptide solubility and increased the molecular weight,
      enabling sensitive detection by FCS. Using the labeled substrates, caspase-3 and
      matrix metalloproteinase-9 (MMP-9) activities were confirmed by FCS. To
      demonstrate the suitability of this FCS-based assay for high-throughput
      screening, we screened various chemical compounds for MMP-9 inhibitors. The
      screening results confirmed the inhibitory activity of one compound and also
      revealed another potential MMP-9 inhibitor. Thus, this combination of position
      specific labeled protein substrates and FCS may serve as a useful tool for
      evaluating activities of various proteases and for protease inhibitor screening.

PMID- 19394305
TI  - Binding of amphipathic alpha-helical antimicrobial peptides to lipid membranes:
      lessons from temporins B and L.
AB  - Temporins constitute a family of amphipathic alpha-helical antimicrobial peptides
      (AMP) and contain some of the shortest cytotoxic peptides, comprised of only 10
      14 residues. General characteristics of temporins parallel those of other AMP,
      both in terms of structural features and biophysical properties relating to their
      interactions with membrane lipids, with selective lipid-binding properties
      believed to underlie the discrimination between target vs host cells. Lipid
      binding properties also contribute to the cytotoxicity AMP, causing
      permeabilization of their target cell membranes. The latter functional property
      of AMP involves highly interdependent acidic phospholipid-induced conformational
      changes, aggregation, and formation of toxic oligomers in the membrane. These
      oligomers are subsequently converted to amyloid-type fibers, as demonstrated for
      e.g. temporins B and L in our laboratory, and more recently for dermaseptins by
      Auvynet et al. Amyloid state represents the generic minimum in the
      folding/aggregation free energy landscape, and for AMP its formation most likely
      serves to detoxify the peptides, in keeping with the current consensus on mature
      amyloid being inert and non-toxic. The above scenario is supported by sequence
      analyses of temporins as well as other amphipathic alpha-helical AMP belonging to
      diverse families. Accordingly, sequence comparison identifies 'conformational
      switches', domains with equal probabilities for adopting random coil, alpha
      helical and beta-sheet structures. These regions were further predicted also to
      aggregate and assemble into amyloid beta-sheets. Taken together, the lipid
      binding properties and structural characterization lend support to the notion
      that the mechanism of membrane permeabilization by temporins B and L and perhaps
      of most AMP could be very similar, if not identical, to that of the paradigm
      amyloid forming cytotoxic peptides, responsible for degenerative cell loss in
      e.g. prion, Alzheimer's and Parkinson's disease, and type 2 diabetes.

PMID- 19394306
TI  - Expression and stability of the nontoxic component of the botulinum toxin
      complex.
AB  - Clostridium botulinum produces botulinum neurotoxin (BoNT) as a large toxin
      complex associated with nontoxic-nonhemagglutinin (NTNHA) and/or hemagglutinin
      components. In the present study, high-level expression of full-length (1197
      amino acids) rNTNHA from C. botulinum serotype D strain 4947 (D-4947) was
      achieved in an Escherichia coli system. Spontaneous nicking of the rNTNHA at a
      specific site was observed during long-term incubation in the presence of
      protease inhibitors; this was also observed in natural NTNHA. The rNTNHA
      assembled with isolated D-4947 BoNT with molar ratio 1:1 to form a toxin complex.
      The reconstituted toxin complex exhibited dramatic resistance to proteolysis by
      pepsin or trypsin at high concentrations, despite the fact that the isolated BoNT
      and rNTNHA proteins were both easily degraded. We provide definitive evidence
      that NTNHA plays a crucial role in protecting BoNT, which is an oral toxin, from
      digestion by proteases common in the stomach and intestine.

PMID- 19394307
TI  - Syndecan-2 overexpression regulates adhesion and migration through cooperation
      with integrin alpha2.
AB  - Syndecan-2, a transmembrane heparan sulfate proteoglycan, is known to serve as an
      adhesion receptor, but details of the regulatory mechanism governing syndecan-2
      cell adhesion and migration remain unclear. Here, we examined this regulatory
      mechanism, showing that overexpression of syndecan-2 enhanced collagen adhesion,
      cell migration and invasion of normal rat intestinal epithelial cells (RIE1), and
      increased integrin alpha2 expression levels. Interestingly, RIE1 cells
      transfected with either syndecan-2 or integrin alpha2 showed similar adhesion and
      migration patterns, and a function-blocking anti-integrin alpha2 antibody
      abolished syndecan-2-mediated adhesion and migration. Consistent with these
      findings, transfection of integrin alpha2 siRNA diminished syndecan-2-induced
      cell migration in HCT116 human colon cancer cells. Taken together, these results
      demonstrate a novel cooperation between syndecan-2 and integrin alpha2beta1 in
      adhesion-mediated cell migration and invasion. This interactive dynamic might be
      a possible mechanism underlying the tumorigenic activities of colon cancer cells.

PMID- 19394308
TI  - OCT4A contributes to the stemness and multi-potency of human umbilical cord blood
      derived multipotent stem cells (hUCB-MSCs).
AB  - The OCT4A gene, a POU homeodomain transcription factor, has been shown to be
      expressed in embryonic stem cells (ESC) as well as hUCB-MSCs. In this study, the
      roles played by OCT4A in hUCB-MSCs were determined by stably inhibiting OCT4A
      with lenti-viral vector-based small hairpin RNA (shRNA). A decreased rate of cell
      proliferation was observed in OCT4-inhibited hUCB-MSCs. Down-regulation of CCNA2
      expression in OCT4-inhibited hUCB-MSCs was confirmed by RT-PCR and real-time RT
      PCR analysis in three genetically independent hUCB-MSC clones. Adipogenic
      differentiation was also suppressed in OCT4-inhibited hUCB-MSCs. The up
      regulation of DTX1 and down-regulation of HDAC1, 2, and 4 expressions may be
      related to this differentiation deformity. The expression of other transcription
      factors, including SOX2, REX1 and c-MYC, was also affected by OCT4 inhibition in
      hUCB-MSCs. In conclusion, these finding suggest that OCT4A performs functionally
      conserved roles in hUCB-MSCs, making its expression biologically important for ex
      vivo culture of hUCB-MSCs.

PMID- 19394309
TI  - Duplication of the caspase-12 prodomain and inactivation of NLRC4/IPAF in the
      dog.
AB  - Caspases-1, 4, 5, and 12 and other proteins containing caspase recruitment
      domains (CARDs) play crucial roles in the induction of inflammatory processes.
      Recently, hybrid caspase-1/4 mRNAs encoding proteases with two CARDs were
      identified in cat and dog, indicating that the molecular machinery of caspase
      dependent inflammation has an unconventional composition in members of the order
      Carnivora. Here we extended these studies and identified, both in cat and dog,
      splice variants of caspase-12, which also contained two CARDs. Comparative
      genomics analysis of the repertoire of canine CARD proteins revealed that the
      gene encoding NLRC4/IPAF, which is implicated in the inflammatory response to
      cytosolic flagellin, was inactivated by deleterious mutations in the dog. Our
      results demonstrate that the repertoires of CARD proteins in cat and dog differ
      significantly from that of humans and suggest the existence of uncharacterized
      pathways of inflammasome-mediated signaling in Carnivora.

PMID- 19394310
TI  - Prediction of functionally important sites from protein sequences using sparse
      kernel least squares classifiers.
AB  - Identification of functionally important sites (FIS) in proteins is a critical
      problem and can have profound importance where protein structural information is
      limited. Machine learning techniques have been very useful in successful
      classification of many important biological problems. In this paper, we adopt the
      sparse kernel least squares classifiers (SKLSC) approach for classification
      and/or prediction of FIS using protein sequence derived features. The SKLSC
      algorithm was applied to 5435 FIS that have been extracted from 312 reliable
      alignments for a wide range of protein families. We obtained 68.28% sensitivity
      and 68.66% specificity for training dataset and 65.34% sensitivity and 66.88%
      specificity for testing dataset. Further, large scale benchmarking study using
      alignments of 101 protein families containing 1899 FIS showed that our method
      achieved an average approximately 70% sensitivity in predicting different types
      of FIS, such as active sites, metal, ligand or protein binding sites. Our
      findings also indicate that active sites and metal binding sites are comparably
      easier to predict compared to the ligand and protein binding sites. Despite
      moderate success, our results suggest the usefulness and potential of SKLSC
      approach in prediction of FIS using only protein sequence derived information.

PMID- 19394311
TI  - Flow cytometric analysis of the calcitonin receptor-like receptor domains
      responsible for cell-surface translocation of receptor activity-modifying
      proteins.
AB  - The three receptor activity-modifying proteins (RAMPs1, -2, and -3) associate
      with a wide variety of G protein-coupled receptors (GPCRs), including calcitonin
      receptor-like receptor (CRLR). In this study, we used flow cytometry to measure
      RAMP translocation to the cell surface as a marker of RAMP-receptor interaction.
      Because VPAC2 does not interact with RAMPs, although, like CRLR, it is a Family B
      peptide hormone receptor, we constructed a set of chimeric CRLR/VPAC2 receptors
      to evaluate the trafficking interactions between CRLR domains and each RAMP. We
      found that CRLR regions extending from transmembrane domain 1 (TM1) through TM5
      are necessary and sufficient for the transport of RAMPs to the plasma membrane.
      In addition, the extracellular N-terminal domain of CRLR, its 3rd intracellular
      loop and/or TM6 were also important for the cell-surface translocation of RAMP2,
      but not RAMP1 or RAMP3. Other regions within CRLR were not involved in
      trafficking interactions with RAMPs. These findings provide new insight into the
      trafficking interactions between accessory proteins such as RAMPs and their
      receptor partners.

PMID- 19394312
TI  - Renal organic anion transporters OAT1 and OAT3 mediate the cellular accumulation
      of 5-sulfooxymethylfurfural, a reactive, nephrotoxic metabolite of the Maillard
      product 5-hydroxymethylfurfural.
AB  - 5-Hydroxymethylfurfural (HMF) is formed when sugars are acidified or heated. It
      is present at high levels in numerous foods. HMF is inactive in standard
      genotoxicity tests, but can be metabolized to a chemically reactive intermediate,
      5-sulfooxymethylfurfural (SMF), which is mutagenic and carcinogenic. We recently
      found that direct parental administration of SMF to mice leads to abundant acute
      necrosis and proteinaceous casts in the proximal tubules as the dominating
      toxicological effect. Since proximal tubule cells actively mediate the excretion
      of many organic anions, we hypothesized that transporter-mediated uptake of SMF
      into the cells could be the reason for this selective organotoxicity. To test
      this hypothesis, we used human embryonic kidney (HEK293) cells stably expressing
      human (h) OAT1 or OAT3. SMF was a competitive inhibitor of p-aminohippurate
      uptake by hOAT1 and estrone sulfate uptake by hOAT3 with K(i) values of 225
      microM and 1.5mM, respectively. Moreover, the initial rates of SMF uptake were
      5.2- and 3.1-fold higher in cells expressing hOAT1 and hOAT3, respectively, than
      in control HEK293 cells. Likewise, the sensitivity of hOAT1- and hOAT3-expressing
      cells to SMF cytotoxicity was significantly higher than that of control cells,
      and was reduced by addition of probenecid, an inhibitor of OATs. Taken together,
      these results indicate that OAT1 and OAT3 mediate the uptake of SMF into proximal
      tubule cells and thereby may be involved in SMF-induced nephrotoxicity.

PMID- 19394313
TI  - Antimelanoma activity of the redox dye DCPIP (2,6-dichlorophenolindophenol) is
      antagonized by NQO1.
AB  - Altered redox homeostasis involved in the control of cancer cell survival and
      proliferative signaling represents a chemical vulnerability that can be targeted
      by prooxidant redox intervention. Here, we demonstrate that the redox dye 2,6
      dichlorophenolindophenol (DCPIP) may serve as a prooxidant chemotherapeutic
      targeting human melanoma cells in vitro and in vivo. DCPIP-apoptogenicity
      observed in the human melanoma cell lines A375 and G361 was inversely correlated
      with NAD(P)H:quinone oxidoreductase (NQO1) expression levels. In A375 cells
      displaying low NQO1 activity, DCPIP induced apoptosis with procaspase-3 and PARP
      cleavage, whereas G361 cells expressing high levels of enzymatically active NQO1
      were resistant to DCPIP-cytotoxicity. Genetic (siRNA) or pharmacological
      (dicoumarol) antagonism of NQO1 strongly sensitized G361 cells to DCPIP
      apoptogenic activity. DCPIP-cytotoxicity was associated with the induction of
      oxidative stress and rapid depletion of glutathione in A375 and NQO1-modulated
      G361 cells. Expression array analysis revealed a DCPIP-induced stress response in
      A375 cells with massive upregulation of genes encoding Hsp70B' (HSPA6), Hsp70
      (HSPA1A), heme oxygenase-1 (HMOX1), and early growth response protein 1 (EGR1)
      further confirmed by immunodetection. Systemic administration of DCPIP displayed
      significant antimelanoma activity in the A375 murine xenograft model. These
      findings suggest feasibility of targeting tumors that display low NQO1 enzymatic
      activity using DCPIP.

PMID- 19394315
TI  - Control of vocalization at utterance onset and mid-utterance: different
      mechanisms for different goals.
AB  - A large body of evidence suggests that the motor system maintains a forward model
      that predicts the sensory outcome of movements. When sensory feedback does not
      match the predicted consequences, a compensatory response corrects for the motor
      error and the forward model is updated to prevent future errors. Like other motor
      behaviours, vocalization relies on sensory feedback for the maintenance of
      forward models. In this study, we used a frequency altered feedback (FAF)
      paradigm to study the role of auditory feedback in the control of vocal pitch
      (F0). We adapted subjects to a one semitone shift and induced a perturbation by
      briefly removing the altered feedback. This was compared to a control block in
      which a 1 semitone perturbation was introduced into an unshifted trial, or trials
      were randomly shifted up 1 semitone, and a perturbation was introduced by
      removing the feedback alteration. The compensation response to mid-utterance
      perturbations was identical in all conditions, and was always smaller than the
      compensation to a shift at utterance onset. These results are explained by a
      change in the control strategy at utterance onset and mid-utterance. At utterance
      onset, auditory feedback is compared to feedback predicted by a forward model to
      ensure the pitch goal is achieved. However, after utterance onset, the control
      strategy switches and stabilization is maintained by comparing feedback to
      previous F0 production.

PMID- 19394314
TI  - Crystal structures of human group-VIIA phospholipase A2 inhibited by
      organophosphorus nerve agents exhibit non-aged complexes.
AB  - The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in
      human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid
      substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase
      superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs
      ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve
      synapses, but may additionally have detrimental effects through inhibition of
      other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2
      following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and
      tabun. The sarin and soman complexes displayed a racemic mix of P(R) and P(S)
      stereoisomers at the P-chiral center. The tabun complex displayed only the P(R)
      stereoisomer in the crystal. In all cases, the crystal structures contained
      intact OP adducts that had not aged. Aging refers to a secondary process OP
      complexes can go through, which dealkylates the nerve agent adduct and results in
      a form that is highly resistant to either spontaneous or oxime-mediated
      reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin
      digest and matrix-assisted laser desorption ionization mass spectrometry of OP
      enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed
      by gas chromatography/mass spectrometry using a chiral column to separate and
      quantitate the unbound stereoisomers of sarin following incubation with enzyme.
      The structural details and characterization of nascent reactivity of several
      toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as
      a catalytic bioscavenger of OP nerve agents.

PMID- 19394316
TI  - Differential methotrexate hepatotoxicity on rat hepatocytes in 2-D monolayer
      culture and 3-D gel entrapment culture.
AB  - It has been reported that 3-D cultures of hepatocytes or HepG2 cells were less
      susceptible to methotrexate (MTX) than their 2-D counterparts. Such a mechanism
      was addressed in this study by investigation of MTX hepatotoxicity in gel
      entrapped (3-D) rat hepatocytes vs. traditional monolayer culture (2-D).
      Similarly, gel entrapped hepatocytes showed higher drug resistance to MTX than
      hepatocyte monolayers in whatever culture medium with or without modification by
      hormone supplements (dexamethasone, glucagon and insulin). It was also found that
      medium modification by hormones greatly increased drug resistance of hepatocyte
      monolayers but has only a slight effect on 3-D cultured hepatocytes. These
      differential MTX toxicities regarding culture medium and culture models were
      assumed to correlate with multidrug resistance associated protein 2 (Mrp2). The
      involvement of Mrp2 was confirmed directly by the fact that MTX intracellularly
      accumulated less in gel entrapped hepatocytes than in hepatocyte monolayer but
      could be enhanced by Mrp2 inhibitors accompanied by reduced drug resistance.
      Furthermore, the expression of Mrp2 on gene level and transportation activity
      together with bile-duct-like structure were more significantly evidenced in 3-D
      gel entrapment culture than in 2-D monolayer culture. In conclusion, the highly
      preserved Mrp2 in 3-D gel entrapped hepatocytes determines its high drug
      resistance to MTX. Gel entrapped hepatocytes could be useful for investigation of
      hepatic transportation and hepatotoxicity.

PMID- 19394317
TI  - Clotrimazole enhances lysis of human erythrocytes induced by t-BHP.
AB  - Clotrimazole (CLT) is an antifungal and antimalarial agent also effective as a
      Gardos channel inhibitor. In addition, CLT possesses antitumor properties. Recent
      data provide evidence that CLT forms a complex with heme (hemin), which produces
      a more potent lytic effect than heme alone. This study addressed the effect of
      CLT on the lysis of normal human erythrocytes induced by tert-butyl hydroperoxide
      (t-BHP). For the first time, it was shown that 10 microM CLT significantly
      enhanced the lytic effect of t-BHP on erythrocytes in both Ca(2+)-containing and
      Ca(2+)-free media, suggesting that the effect is not related to Gardos channels.
      CLT did not affect the rate of free radical generation, the kinetics of GSH
      degradation, methemoglobin formation and TBARS generation; therefore, we
      concluded that CLT does not cause additional oxidative damage to erythrocytes
      treated with t-BHP. It is tempted to speculate that CLT enhances t-BHP-induced
      changes in erythrocyte volume and lysis largely by forming a complex with hemin
      released during hemoglobin oxidation in erythrocytes: the CLT-hemin complex
      destabilizes the cell membrane more potently than hemin alone. If so, the effect
      of CLT on cell membrane damage during free-radical oxidation may be used to
      increase the efficacy of antitumor therapy.

PMID- 19394318
TI  - Phase behaviour of oleanolic acid/stearyl stearate binary mixtures in bulk and at
      the air-water interface.
AB  - The solid-liquid phase behaviour of oleanolic acid (OLA)/stearyl stearate (SS)
      was investigated by differential scanning calorimetry and polarizing optical
      microscopy. A eutectic type diagram, with the eutectic composition close to pure
      SS was obtained. Complementary studies by NMR, X-ray diffraction (XRD) and
      diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy were
      performed. A mutual influence was detected in mixtures: the low melting form of
      SS is favoured at low OLA molar fractions (X(OLA)) and spherulitic structures
      appear at high X(OLA) and high temperature. Additionally, H-bonding between OLA
      carbonyl groups increases in the presence of SS. The study of OLA/SS by the
      Langmuir method and Brewster angle microscopy revealed the organization at the
      air-water interface: OLA interacts with water in the first layer, while SS is
      completely segregated to the upper layer for X(OLA)>0.3, and it distributes in
      the first and upper layers for X(OLA)<0.3.

PMID- 19394319
TI  - Urinary porphyrin excretion in normal children and adolescents.
AB  - BACKGROUND: Urinary porphyrins are diagnostic of various metabolic disorders and
      xenobiotic exposures, but comprehensive normative data for urinary porphyrin
      concentrations in children are currently unavailable. METHODS: Subjects were
      participants in a prospective, randomized, controlled clinical trial of dental
      materials safety, 8 to 12 y at inception, who were followed longitudinally for 7
      y after baseline with an extensive battery of neurobehavioral, neurological,
      renal function and urinary porphyrin assessments. Porphyrins were quantified by
      HPLC. Linear regression analyses were used to measure associations of porphyrin
      levels with age and gender. RESULTS: Mean concentrations, 95% confidence
      intervals, and 10th, 50th, and 90th percentiles for all 5 typically excreted
      urinary porphyrins are presented by year of age and by gender. Unadjusted urinary
      concentrations (microg/l) of all 5 porphyrins remained relatively constant
      throughout the age range of 8-18 y for both males and females. In contrast,
      creatinine-adjusted urinary porphyrin concentrations (microg/g) declined
      significantly throughout this age range in both genders. Boys had significantly
      higher pentacarboxyl- and copro-porphyrin levels compared with girls both before
      and after creatinine adjustment. CONCLUSIONS: Normative longitudinal data
      provided herein may facilitate the clinical assessment of pediatric metabolic
      disorders and may be of particular relevance in evaluating porphyrin changes as a
      biological indicator of disease or xenobiotic exposures among children and
      adolescents.

PMID- 19394320
TI  - Serum 3'-sulfo-Lea indication of gastric cancer metastasis.
AB  - BACKGROUND: 3'-Sulfo-Le(a) is known to be the potent ligand of E-selectin which
      is important in cell adhesion and migration. Yet the significance of serum 3'
      sulfo-Le(a) has not been explored and reported. METHODS: Serum 3'-sulfo-Le(a) was
      analyzed by enzyme-linked immunosorbent assay. SPSS software was used for
      statistics analysis. Cell adhesion to HUVEC and sL-selectin, and cell migration
      were performed in gastric cancer cells SCG7901 with 3'-sulfo-Le(a) silence by
      Gal3ST-2 RNAi. RESULTS: Through analysis, the mean levels of serum 3'-sulfo-Le(a)
      antigen were found significantly higher in 108 patients with gastric cancer than
      that in 74 healthy volunteers. Depth of tumor invasion, lymph node metastasis,
      and differentiation were noted to be significantly correlated with the expression
      of this antigen in gastric carcinoma. After treatment with 5-FU (5-fluorouracil)
      and ATRP (N-all-trans-retinoyl-L-proline), the expression of 3'-sulfo-Le(a)
      antigen was markedly down regulated in SCG7901 gastric cancer cells. After
      transfection of Gal3ST-2 RNAi, the expression of 3'-sulfo-Le(a) was silenced and
      the cell adhesion to HUVEC or sL-selectin, and cell migration were suppressed.
      CONCLUSION: Serum 3'-sulfo-Le(a) antigen can provide important information in
      patients with primary gastric cancer, which might be useful as a predictive
      marker especially for the detection of tumor metastasis.

PMID- 19394321
TI  - Increase of macrophage migration inhibitory factor (MIF) expression in
      cardiomyocytes during chronic hypoxia.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) might play an important
      role in the myocardium during chronic hypoxia because MIF protects the heart
      during myocardial ischemia by activating 5'-adenosine monophosphate activated
      protein kinase (AMPK). METHODS: We investigated 35 infants with cyanotic or
      acyanotic cardiac defects and H9c2 embryonic rat cardiomyocytes to examine the
      effect of chronic hypoxia on the expression of MIF in vivo and in vitro,
      respectively. RESULTS: We found out an increase of endogenous cardiac MIF
      expression positively correlated with degree of hypoxia. Also, AMPK activation
      was elevated while MIF expression was increased in cells exposed to long periods
      of hypoxia in vitro. There was no significant difference in the growth ratio of
      cells cultivated in long periods of hypoxia and normoxia. CONCLUSIONS: The
      expression of MIF is significantly increased in cardiomyocytes exposed to chronic
      hypoxia, and the activation of AMPK was increased accordingly.

PMID- 19394322
TI  - Genetic and environmental influences on total plasma homocysteine and coronary
      artery disease (CAD) risk among South Indians.
AB  - BACKGROUND: Hyperhomocysteinemia, a documented risk factor for CAD is highly
      prevalent in Indians. The rationale behind the current study is to explore the
      genetic and environmental causes for such high prevalence as there are limited
      studies in this context. METHODS: A total of 108 CAD cases and 108 controls were
      analyzed for tHcy and 4 folate pathway genetic polymorphisms [methylene
      tetrahydrofolate reductase (MTHFR) C677T, 5-methyltetrahydrofolate homocysteine
      methyl transferase (MTR) A2756G, methionine synthase reductase (MTRR) A66G and
      glutamate carboxypeptidase II (GCPII) C1561T] using reverse phase HPLC and PCR
      RFLP methods respectively. RESULTS: MTHFR 677T, MTRR 66A, GCPII 1561T, male
      gender, alcohol intake, smoking, diabetes, creatinine and hypertension were found
      to influence tHcy. After controlling for confounding factors,
      Hyperhomocysteinemia and two of its genetic determinants i.e. MTHFR C677T [OR:
      1.96, 95% CI: 1.06-3.61] and GCP II C1561T [OR: 2.09, 95% CI: 1.09-3.97] were
      found to be associated with risk for CAD. Significant epistatic interactions were
      observed between MTHFR 677T/MTR 2756G and GCP II 1561T/MTRR 66G. Alcohol intake
      in subjects with MTR 2756G allele was found to inflate the risk for CAD [OR:
      4.15, 95% CI: 1.35-12.69]. CONCLUSION: Hyperhomocysteinemia, C677T MTHFR and
      C1561T GCPII are risk factors for CAD. Potential gene--gene and gene--environment
      interactions indicate the need for multi-variate analyses for risk prediction.

PMID- 19394323
TI  - Fertilization of C57BL/6 mouse sperm collected from cauda epididymides after
      preservation or transportation at 4 degrees C using laser-microdissected oocytes.
AB  - The C57BL/6 mouse is commonly used to produce transgenic and knockout strains for
      biomedical research. However, the motility and fertility of its sperm decrease
      markedly with freezing. Short-term preservation of sperm without freezing can
      avoid this. Furthermore, such samples can be transported safety without the
      special skills or equipment needed for the transportation of live animals or
      frozen products. We evaluated the motility and fertility of sperm collected from
      cauda epididymides after preservation or transportation at 4 degrees C. Oocytes
      with the zona pellucida subjected to laser-microdissection were used to assist
      fertilization in vitro. Although the motility of sperm gradually decreased with
      storage (P<0.05), no disruption of the sperm plasma membrane was seen. The
      proportion of zona-intact oocytes fertilized with sperm preserved for 0, 24, 48
      and 72h were 70, 14, 5 and 1%, respectively. On the other hand, 45, 20 and 14% of
      laser-microdissected oocytes were fertilized by sperm preserved for 24, 48 and
      72h, respectively (P<0.05). The fertility of sperm collected from cauda
      epididymides of two transgenic strains after transportation at 4 degrees C were
      also significantly increased using laser-microdissected oocytes rather than zona
      intact oocytes (57 and 68% vs. 5%, P<0.05). Efficient production of offspring
      from sperm preserved or transported at 4 degrees C was achieved using laser
      microdissected oocytes. Thus the fertility of sperm preserved or transported at 4
      degrees C could be maintained, although motility gradually decreased with
      storage. Laser-microdissected oocytes will contribute to the efficient production
      of embryos and offspring using such preserved sperm samples.

PMID- 19394324
TI  - Effect of chilling on porcine germinal vesicle stage oocytes at the subcellular
      level.
AB  - The potential subcellular consequence of chilling on porcine germinal vesicle
      (GV) stage oocytes was examined. Prior to in vitro maturation (IVM), Cumulus
      oocyte complexes (COCs) freshly collected from antral follicles (3-6mm in
      diameter) were evenly divided into four groups and immediately incubated in PVA
      TL-HEPES medium at the temperature of 39 degrees C (control group), 23 degrees C
      (room temperature), 15 degrees C and 10 degrees C for 10min, respectively.
      Following 42h of IVM at 39 degrees C, the survival rates were examined. There was
      no significant difference between the survival rate of 23 degrees C chilled group
      and control group (77.92 and 91.89%), but the survival rate of 15 and 10 degrees
      C chilled group were significantly decreased (46.34 and 4.81%, P<0.01). A further
      experiment on 15 degrees C group showed that most oocytes died from 2 to 4h of
      IVM. In order to investigate the effects of chilling on oocytes at the
      subcellular level, the control and 15 degrees C chilled group COCs fixed at
      different time points of the IVM cultures (2, 2.5, 3, 3.5 and 4h of IVM) were
      prepared for transmission electron microscope (TEM) observation. As the result,
      compared with the control group, there were two significant changes in the
      ultrastructural morphology of 15 degrees C treatment group: (1) dramatic
      reduction of heterogeneous lipid, (2) disorganized mitochondria-endoplasmic
      reticulum-lipid vesicles (M-E-L) combination. These results indicate that 15
      degrees C is a critical chilling temperature for porcine GV stage oocyte and the
      alteration of cellular chemical composition and the destruction of M-E-L
      combination maybe responsible for chilling injury of porcine oocyte at this
      stage.

PMID- 19394326
TI  - LGR5 deficiency deregulates Wnt signaling and leads to precocious Paneth cell
      differentiation in the fetal intestine.
AB  - The orphan Leucine-rich repeat G protein-coupled receptor 5 (LGR5/GPR49), a
      target of Wnt signaling, is a marker of adult intestinal stem cells (SC).
      However, neither its function in the adults, nor during development of the
      intestine have been addressed yet. In this report, we investigated the role of
      LGR5 during ileal development by using LGR5 null/LacZ-NeoR knock-in mice. X-gal
      staining experiments showed that, after villus morphogenesis, Lgr5 expression
      becomes restricted to dividing cells clustered in the intervillus region and is
      more pronounced in the distal small intestine. At day E18.5, LGR5 deficiency
      leads to premature Paneth cell differentiation in the small intestine without
      detectable effects on differentiation of other cell lineages, nor on epithelial
      cell proliferation or migration. Quantitative RT-PCR experiments showed that
      expression from the LGR5 promoter was upregulated in LGR5-null mice, pointing to
      the existence of an autoregulatory negative feedback loop in intact animals. This
      deregulation was associated with overexpression of Wnt target genes in the
      intervillus epithelium. Transcriptional profiling of mutant mice ileums revealed
      that LGR5 function is associated with expression of SC and SC niche markers.
      Together, our data identify LGR5 as a negative regulator of the Wnt pathway in
      the developing intestine.

PMID- 19394325
TI  - Sonic hedgehog signalling inhibits palatogenesis and arrests tooth development in
      a mouse model of the nevoid basal cell carcinoma syndrome.
AB  - Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant or
      spontaneous disorder characterized by multiple cutaneous basal cell carcinomas,
      odontogenic keratocysts, skeletal anomalies and facial dysmorphology, including
      cleft lip and palate. Causative mutations for NBCCS occur in the PTCH1 gene on
      chromosome 9q22.3-q31, which encodes the principle receptor for the Hedgehog
      signalling pathway. We have investigated the molecular basis of craniofacial
      defects seen in NBCCS using a transgenic mouse model expressing Shh in basal
      epithelium under a Keratin-14 promoter. These mice have an absence of flat bones
      within the skull vault, hypertelorism, open-bite malocclusion, cleft palate and
      arrested tooth development. Significantly, increased Hedgehog signal transduction
      in these mice can influence cell fate within the craniofacial region. In medial
      edge epithelium of the palate, Shh activity prevents apoptosis and subsequent
      palatal shelf fusion. In contrast, high levels of Shh in odontogenic epithelium
      arrests tooth development at the bud stage, secondary to a lack of cell
      proliferation in this region. These findings illustrate the importance of
      appropriately regulated Hedgehog signalling during early craniofacial development
      and demonstrate that oro-facial clefting and hypodontia seen in NBCCS can occur
      as a direct consequence of increased Shh signal activity within embryonic
      epithelial tissues.

PMID- 19394327
TI  - Antinociceptive effects of systemic lidocaine: involvement of the spinal
      glycinergic system.
AB  - Beside their action on voltage-gated Na(+) channels, local anesthetics are known
      to exert a variety of effects via alternative mechanisms. The antinociceptive
      effect of lidocaine is well documented, yet the exact mechanism is not fully
      understood. Whether glycinergic mechanisms, which play a pivotal role in pain
      modulation, are involved in lidocaine-induced antinociception is hitherto
      unclear. In the present study, lidocaine was injected intravenously in rats using
      the formalin test for acute pain and the chronic constriction injury model for
      neuropathic pain. The effect of intrathecally administered d-serine (an agonist
      at the glycine-binding site at the NMDA-receptor), its inactive isomer l-serine,
      CGP 78608 (antagonist at the glycineB-site of the NMDA-receptor) and strychnine
      (antagonist at inhibitory glycine-receptors) on lidocaine-induced antinociception
      was examined. Systemically administered lidocaine was antinociceptive in both
      acute and chronic pain model. In the formalin test, the effect of lidocaine was
      antagonized by d-serine, but not by l-serine or strychnine. In the chronic
      constriction injury model, antinociception evoked by lidocaine was reduced by d
      serine, strychnine and CGP 78608, while l-serine had no effect. These results
      indicate a modulatory effect of lidocaine on the NMDA-receptor. Additionally,
      since in our study lidocaine-induced antinociception was antagonized by both
      glycineB-site modulators and strychnine our results may favor the hypothesis of a
      general glycine-like action of lidocaine or some of its metabolites on inhibitory
      strychnine-sensitive receptors and on strychnine-insensitive glycine receptors.

PMID- 19394328
TI  - Inhibition of rat recombinant GluN1/GluN2A and GluN1/GluN2B NMDA receptors by
      ethanol at concentrations based on the US/UK drink-drive limit.
AB  - Many studies examine the actions of ethanol on N-methyl-D-aspartate (NMDA)
      receptors using concentrations that are highly toxic (>or=100 mM). This study re
      assesses the actions of ethanol at concentrations based around the US/UK 'drink
      drive' limit (17 mM). Using two-electrode voltage-clamp recordings we examined
      the actions of ethanol on recombinant GluN1/GluN2A and GluN1/GluN2B NMDA
      receptors expressed in Xenopus laevis oocytes. We also investigated its actions
      on NMDA receptors containing GluN2A subunits with truncated or deleted carboxy
      terminal domains. Ethanol inhibition was voltage-independent and for GluN1/GluN2A
      NMDA receptors mean inhibition (20 mM at -60 mV) was 9.5+/-0.8% (n=33) while
      corresponding values for GluN1/GluN2B NMDA receptors were 6.5+/-0.8% (n=21).
      EC(50) values for glutamate at GluN1/GluN2A and glutamate and glycine at
      GluN1/GluN2B NMDA receptors were unaffected by the presence of ethanol. We did
      however observe a small increase in glycine potency, in the presence of ethanol,
      at GluN1/GluN2A NMDA receptors. Neither voltage-dependent Mg(2+) block nor
      memantine block was affected by ethanol. Reduced ethanol inhibition was observed
      however at NMDA receptors containing GluN2A subunits with mutated carboxy
      terminal domains. We conclude that the levels of inhibition seen with ethanol
      concentrations near to the US/UK drink-driving limit are very modest and even at
      higher (intoxicating) concentrations do not alter characteristic NMDA receptor
      properties.

PMID- 19394329
TI  - The effect of vinca alkaloid anticancer drug, vinorelbine, on chromatin and
      histone proteins in solution.
AB  - Vinorelbine (navelbin) belongs to vinca alkaloid anticancer drugs family with a
      broad spectrum of selective activity against mitotic microtubules. The present
      study is the first report demonstrating chromatin components as a novel target
      for vinorelbine in hepatocytes. The interaction was carried out in solution,
      employing fluorescence, UV spectroscopy and thermal denaturation techniques.
      Fluorescence emission spectra represented quenching of DNA chromospheres with
      drug and decreased fluorescence emission intensity in a dose-dependent manner.
      Binding of vinorelbine to chromatin induced very high hypochromicity and shifted
      DNA melting temperature to lower Tm. Vinorelbine binds to histone proteins with
      very high affinity when compared with the interaction of DNA intercalator
      anticancer drug, daunomycin, and the globular domain of the histones is
      considered as a main drug binding site. The results also showed that in the
      presence of vinorelbine, the absorbance of chromatin at 260 nm was decreased and
      the binding pattern was similar to daunomycin-chromatin complex. The results for
      the first time suggest that apart from tubulins, chromatin components can also be
      considered as a new target for this anticancer drug.

PMID- 19394331
TI  - Adhesion and transcellular migration of neutrophils and B lymphocytes on
      fibroblasts.
AB  - During tissue inflammation, infiltrated leukocytes may have physical contacts
      with fibroblasts. We observed that neutrophils and B lymphocytes adhered in a
      larger proportion than T cells on cultured fibroblasts. Microscopy showed that
      adhesion was also characterized by leukocyte engulfment by the fibroblasts. In
      migration assays, only neutrophils and B lymphocytes were selectively able to
      migrate through a fibroblast barrier. Adhesion and migration were increased by
      stimulation with tumor necrosis factor-alpha (TNF-alpha) and phorbol-12-myristate
      13-acetate (PMA). Antibodies against ICAM-1/beta2 integrin blocked the
      interaction of neutrophils to fibroblasts. For B lymphocytes the couple VCAM
      1/alpha4 integrin was also involved in this interaction. Human skin fibroblasts
      presented similar adhesion characteristics as rat cardiac fibroblasts. By
      measuring the distance between the border of migration holes and cadherin
      positive adherens junctions, more than 65% of the holes correspond to the
      transcellular route over the paracellular route. Furthermore, vimentin staining
      revealed that the migration holes were highly nested by intermediate filaments in
      accordance with the transcellular route. Our results demonstrated that engulfment
      of neutrophils and B lymphocytes by fibroblasts resulted in selective passage by
      a transcellular route.

PMID- 19394330
TI  - Oxidation by trace Cu2+ ions underlies the ability of ascorbate to induce
      vascular dysfunction in the rat perfused mesentery.
AB  - Ascorbate has both antioxidant and pro-oxidant activities. We have previously
      shown that plasma levels of ascorbate induce constriction and blockade of
      dilatation mediated by endothelium-derived hyperpolarizing factor (EDHF). In this
      study we sought to determine if these detrimental actions were mediated by a
      prooxidant action of ascorbate. Since trace levels of transition metal ions
      including, Cu2+ and Fe3+, promote oxidation of ascorbate, we examined the effects
      of the chelating agents, cuprizone and deferoxamine, and of CuSO4 and FeCl3 on
      ascorbate-induced constriction and blockade of EDHF in the perfused rat
      mesentery. Cuprizone abolished and Cu2+ but not Fe3+ ions enhanced both ascorbate
      (50 microM)-induced constriction and blockade of EDHF. The blockade of EDHF
      produced by ascorbate in the presence of CuSO4 (0.5 microM) was abolished by the
      hydrogen peroxide scavenger, catalase, but unaffected by the scavengers of
      hydroxyl radical or superoxide anion, mannitol and superoxide dismutase (SOD),
      respectively. Consistent with these observations, the oxidation of ascorbate by
      CuSO4 led to the rapid production of hydrogen peroxide. Catalase, mannitol and
      SOD had no effect on ascorbate-induced constriction. Thus, in the rat perfused
      mesentery, both the constrictor and EDHF-blocking actions of ascorbate arise from
      its oxidation by trace Cu2+ ions. The blockade of EDHF results from the
      consequent generation of hydrogen peroxide, but the factor producing constriction
      remains unidentified. These detrimental actions of ascorbate may help explain the
      disappointing outcome of clinical trials investigating dietary supplementation
      with the vitamin on cardiovascular health.

PMID- 19394332
TI  - ITF-2 is disrupted via allelic loss of chromosome 18q21, and ITF-2B expression is
      lost at the adenoma-carcinoma transition.
AB  - BACKGROUND & AIMS: The ubiquitously expressed basic helix-loop-helix
      transcription factor ITF-2B has an important role in differentiation processes,
      and its transcription is regulated by beta-catenin. The ITF-2 gene is located in
      the chromosomal region 18q21; allelic loss of this locus occurs in 70% of
      colorectal cancers. We analyzed the expression, regulation, and function of ITF
      2B in colorectal carcinogenesis. METHODS: The loss-of-heterozygosity (LOH) status
      of 18q21 and expression of ITF-2B were studied in colorectal carcinomas using
      polymerase chain reaction-based methods and immunohistochemistry. The biologic
      effects of ITF-2B were studied in colorectal cancer cells. Reporter gene assays
      and chromatin immunoprecipitation were utilized to analyze effects of ITF-2B on
      gene transcription. RESULTS: ITF-2B is strongly expressed in colon adenomas but
      frequently down-regulated in carcinomas because of LOH at 18q21. ITF-2B induces
      cell cycle arrest and regulates the expression of p21(Cip1) via newly identified
      E-boxes in the CDKN1A gene, independently of p53. Loss of ITF-2B expression
      correlates with loss of p21(Cip1) expression in primary colon carcinomas.
      CONCLUSIONS: Accumulation of mutations and allelic losses are driving forces of
      colorectal carcinogenesis. ITF-2B, which is up-regulated during early colorectal
      carcinogenesis because of loss of adenomatous polyposis coli, is a target for LOH
      on chromosome 18q, along with deleted in colorectal carcinoma and Smad4. This
      finding, along with the fact that ITF-2B is a regulator of the key cell cycle
      inhibitor p21(Cip1), indicates that ITF-2B is a tumor suppressor that has an
      important function at the adenoma to carcinoma transition.

PMID- 19394333
TI  - Amphipathic DNA polymers inhibit hepatitis C virus infection by blocking viral
      entry.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) gains entry into susceptible cells by
      interacting with cell surface receptor(s). Viral entry is an attractive target
      for antiviral development because of the highly conserved mechanism. METHODS: HCV
      culture systems were used to study the effects of phosphorothioate
      oligonucleotides (PS-ONs), as amphipathic DNA polymers (APs), on HCV infection.
      The in vivo effects of APs were tested in urokinase plasminogen activator
      (uPA)/severe combined immunodeficient (SCID) mice engrafted with human
      hepatocytes. RESULTS: We show the sequence-independent inhibitory effects of APs
      on HCV infection. APs were shown to potently inhibit HCV infection at
      submicromolar concentrations. APs exhibited a size-dependent antiviral activity
      and were equally active against HCV pseudoparticles of various genotypes. Control
      phosphodiester oligonucleotide (PO-ON) polymer without the amphipathic structure
      was inactive. APs had no effect on viral replication in the HCV replicon system
      or binding of HCV to cells but inhibited viral internalization, indicating that
      the target of inhibition is at the postbinding, cell entry step. In uPA/SCID mice
      engrafted with human hepatocytes, APs efficiently blocked de novo HCV infection.
      CONCLUSIONS: Our results demonstrate that APs are a novel class of antiviral
      compounds that hold promise as a drug to inhibit HCV entry.

PMID- 19394334
TI  - Inflammation and intestinal metaplasia of the distal esophagus are associated
      with alterations in the microbiome.
AB  - BACKGROUND & AIMS: Gastroesophageal reflux causes inflammation and intestinal
      metaplasia and its downstream sequelum adenocarcinoma in the distal esophagus.
      The incidence of esophageal adenocarcinoma has increased approximately 6-fold in
      the United States since the 1970s, accompanied with a significant increase in the
      prevalence of gastroesophageal reflux disease (GERD). Despite extensive
      epidemiologic study, the cause for GERD and the unexpected increases remain
      unexplainable. Microbes are among the environmental factors that may contribute
      to the etiology of GERD, but very little research has been done on the esophageal
      microbiome, particularly in its relation to GERD. This is the first comprehensive
      reported correlation between a change in the esophageal microbiome and esophageal
      diseases. METHODS: Biopsy samples of the distal esophagus were collected from 34
      patients. Host phenotypes were histologically defined as normal, esophagitis, or
      Barrett's esophagus (intestinal metaplasia). Microbiomes from the biopsy samples
      were analyzed by bacterial 16S ribosomal RNA gene survey and classified into
      types using unsupervised cluster analysis and phenotype-guided analyses.
      Independence between host phenotypes and microbiome types were analyzed by Fisher
      exact test. RESULTS: Esophageal microbiomes can be classified into 2 types. The
      type I microbiome was dominated by the genus Streptococcus and concentrated in
      the phenotypically normal esophagus. Conversely, the type II microbiome contained
      a greater proportion of gram-negative anaerobes/microaerophiles and primarily
      correlated with esophagitis (odds ratio, 15.4) and Barrett's esophagus (odds
      ratio, 16.5). CONCLUSIONS: In the human distal esophagus, inflammation and
      intestinal metaplasia are associated with global alteration of the microbiome.
      These findings raise the issue of a possible role for dysbiosis in the
      pathogenesis of reflux-related disorders.

PMID- 19394335
TI  - Increased colorectal cancer incidence in obligate carriers of heterozygous
      mutations in MUTYH.
AB  - BACKGROUND & AIMS: MUTYH-associated polyposis (MAP) is an autosomal recessive
      disorder caused by mutations in the MUTYH gene. Patients with MAP are at
      extremely high risk of colorectal cancer, but the risks of colorectal and other
      cancers in heterozygous carriers of a single MUTYH mutation are uncertain. We
      performed a retrospective study of cancer incidence and causes of death among
      obligate MUTYH heterozygote individuals. METHODS: MAP index cases were identified
      from polyposis registers in Germany, The Netherlands, and the United Kingdom.
      Cancer incidence, cancer mortality, and all-cause mortality data were collected
      from 347 parents of unrelated MAP index cases and the spouses of 3 index cases
      who were also found to be heterozygous for single MUTYH mutations. These data
      were compared with appropriate national sex-, age-, and period-specific
      population data to obtain standardized mortality ratios (SMR) and standardized
      incidence ratios (SIR). RESULTS: There was a 2-fold increase in the incidence of
      colorectal cancer among parents of MAP cases, compared with the general
      population (SIR, 2.12; 95% confidence interval [CI]: 1.30-3.28). Their colorectal
      cancer mortality was not increased significantly (SMR, 1.02; 95% CI: 0.41-2.10)
      nor was overall cancer risk (SIR, 0.92; 95% CI: 0.70-1.18), cancer mortality
      (SMR, 1.12; 95% CI: 0.83-1.48), or overall mortality (SMR, 0.94; 95% CI: 0.80
      1.08). CONCLUSIONS: The risk of colorectal cancer in heterozygous carriers of
      single MUTYH mutations who are relatives of patients with MAP is comparable with
      that of first-degree relatives of patients with sporadic colorectal cancer.
      Screening measures should be based on this modest increase in risk.

PMID- 19394336
TI  - Profile of tumor antigen-specific CD8 T cells in patients with hepatitis B virus
      related hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Tumor and viral antigens are expressed by hepatocellular
      carcinoma (HCC) in patients with chronic hepatitis B, but little is known about
      the immunodominance and function of tumor- and virus-specific CD8+ T cells in
      these patients. METHODS: HLA-A2-restricted T-cell responses to 16 tumor antigens
      and hepatitis B virus (HBV) proteins were tested using 49 previously described
      epitopes. Cells from 30 HLA-A2+, HBV-infected patients (10 with HCC, 10 with HBV
      cirrhosis, and 10 HBV but no cirrhosis) were analyzed, after expansion, by enzyme
      linked immunosorbent spot (ELISPOT). Interferon (IFN)-gamma, tumor necrosis
      factor (TNF)-alpha, and interleukin (IL)-2 production, as well as expression of
      the degranulation marker CD107a on tumor-specific CD8+ T cells, were evaluated.
      RESULTS: Cells from all groups had tumor-specific responses. The tumor antigens
      NY-ESO-1 and SSX-2 were most frequently targeted and were immunogenic in the HLA
      A2 subtypes that are characteristic of Asian ethnicity. Tumor-specific T cells
      had low affinities; T cells from non-HCC patients were polyfunctional (IFN
      gamma+, TNF-alpha+, CD107a+) and those from HCC patients displayed an exhausted
      phenotype (IFN-gamma+, CD107a+). Programmed Death 1 (PD-1) was expressed at
      higher levels on T cells from tumor and liver than peripheral blood from HCC
      patients and might contribute to T-cell exhaustion. Blocking PD-1/PD-L1 increased
      the frequency of tumor-specific T cells in HCC patients but did not restore T
      cell function. CONCLUSIONS: Patients with or without HCC have a quantitative and
      functional hierarchy of tumor-specific T cells. HLA-A2-restricted T cells from
      HCC patients target NY-ESO-1, but exist in an exhausted state that might require
      additional activation to restore function.

PMID- 19394337
TI  - Protein kinase C signalling during miracidium to mother sporocyst development in
      the helminth parasite, Schistosoma mansoni.
AB  - For schistosomes, development of the miracidium to mother sporocyst within a
      compatible molluscan host requires considerable physiological and morphological
      changes by the parasite. The molecular mechanisms controlling such development
      have not been explored extensively. To begin to elucidate the importance of
      kinase-mediated signal transduction to this process, the phosphorylation
      (activation) of protein kinase C (PKC) in larval stages of Schistosoma mansoni
      undergoing in vitro transformation was explored. Mining of the S. mansoni genomic
      database revealed two S. mansoni PKC proteins with high homology to human PKCbeta
      and containing the conserved autophosphorylation (activation) site represented by
      serine 660 of human PKCbeta(II). Western blotting with anti-phosphospecific
      antibodies directed to this site demonstrated that miracidia freshly-hatched from
      eggs possessed PKC (78kDa) which was phosphorylated (activated) when miracidia
      were exposed to phorbol ester, and dephosphorylated (inhibited) following
      exposure to the PKC inhibitor GF109203X. Miracidia treated with the phospholipase
      C (PLC) inhibitor U73122 also displayed decreased PKC phosphorylation. S. mansoni
      PKC was phosphorylated during the initial 24h development of miracidia into
      mother sporocysts; after 31h and 48h development, phosphorylation was reduced by
      72% and 86%, respectively. Confocal microscopy of miracidia revealed
      phosphorylated PKC associated with the neural mass, excretory vesicle, tegument,
      ciliated plates, terebratorium and germinal cells; in larvae undergoing
      transformation for 31h, phosphorylated PKC was only occasionally detected, being
      present in regions likely corresponding to the ridge cyton. Inhibition of PKC in
      miracidia by GF109230X resulted in accelerated transformation, particularly to
      the postmiracidium stage; ciliated plates were also shed from developing larvae
      more rapidly. These results highlight the dynamic nature of PKC signalling during
      S. mansoni postembryonic development and support a role for active PKC in
      restricting transformation of S. mansoni miracidia into mother sporocysts.

PMID- 19394338
TI  - EDTA plasma is unsuitable for in vivo determinations of platelet-derived
      angiogenic cytokines.

PMID- 19394339
TI  - Identification by GC-EAD of the two-component trail-following pheromone of
      Prorhinotermes simplex (Isoptera, Rhinotermitidae, Prorhinotermitinae).
AB  - GC/MS analysis confirmed that neocembrene is the major component of the trail
      pheromone in the three species of the termite genus Prorhinotermes (P. simplex,
      P. canalifrons, P. inopinatus). In addition, EAG and GC-EAD experiments with P.
      simplex strongly suggest that dodecatrienol is a quantitatively minor component
      but a qualitatively important component of this trail pheromone. Trail-following
      bioassays confirmed the two-component nature of the trail pheromone. This is the
      first report of the use of the GC-EAD for the identification of trail pheromone
      in termites. These original results underline once again the special phylogenetic
      status of the Prorhinotermitinae among Rhinotermitidae.

PMID- 19394340
TI  - UV tolerance in the two-spotted spider mite, Tetranychus urticae.
AB  - The two-spotted spider mite, Tetranychus urticae was exposed to UV-C (250 nm), UV
      B (300 nm), and UV-A (350 nm). In non-diapausing females, the median effective
      doses for 50% mortality plus escape incidence (ED(50)) were 21 (UV-C) and 104
      kJm(-2) (UV-B); those for 50% oviposition rate in continuous darkness-treated
      mites were 6.2 (UV-C) and 41 kJm(-2) (UV-B). No significant effects of UV-A on
      mortality and oviposition rate were observed. The ED(50) values for UV-B were
      similar to the natural UV-B observed for 2-5 days in summer when T. urticae
      inhabits the undersides of leaves. Therefore, T. urticae possibly uses leaves as
      a filter to avoid the deleterious effects of UV-B. In diapausing females, low
      mortality was observed even at high doses of UV radiation, but more than half
      escaped even at low doses. The orange body color of diapausing females results
      from accumulation of carotenoids, a scavenger for UV-induced reactive oxygen
      species; this may explain the low mortality of diapausing females. Diapausing
      females may overcome the deleterious effects of UV-B during winter in the absence
      of leaves by emigrating to UV-free environments and by accumulating carotenoids.

PMID- 19394341
TI  - Characterization of vitellin protein in the twospotted spider mite, Tetranychus
      urticae (Acari: Tetranychidae).
AB  - In mites, vitellogenin synthesis, regulation and uptake by the oocytes as
      vitellin remain practically unknown. Although a partial sequence of the gene is
      now available, no previous studies have been conducted that describe the native
      vitellin protein in mites. The objective of this study was to characterize
      vitellin in the twospotted spider mite, Tetranychus urticae. The native
      twospotted spider mite vitellin migrated as a single major band with a molecular
      weight of 476+/-14.5 kDa as compared to 590+/-25.5 kDa for vitellin from the
      American dog tick, Dermacentor variabilis. However, isoelectric focusing analysis
      of native spider mite vitellin showed five bands with pI values slightly acidic
      to neutral (pH 5.8, 6.2, 6.7, 7.0 and 7.2), as is the case for insect and tick
      vitellins. Reducing conditions (SDS-PAGE) also revealed multiple subunits ranging
      from 290.9 to 3.6 kDa and was similar to that found in D. variabilis. Spider mite
      vitellin weakly bound lipids and carbohydrates compared to the tick. Unlike D.
      variabilis, the spider mite egg yolk protein does not bind heme. The significance
      of non-heme binding in mites is discussed.

PMID- 19394343
TI  - Distribution of the pacemaker HCN4 channel mRNA and protein in the rabbit
      sinoatrial node.
AB  - Several studies of the pacemaker mechanisms in mammalian cells, most of which
      were carried out in cells isolated from the rabbit sinoatrial node (SAN), have
      highlighted the role of the I(f) current. While the distribution of
      Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels, the molecular
      correlates of f-channels, is known at the mRNA level, the identification of f
      channel proteins in this tissue is still undetermined. Here we investigate HCN
      protein expression in the rabbit pacemaker region. We found that HCN4 is the main
      isoform, and set therefore to analyze its distribution within the SAN and
      surrounding areas with the aim of correlating protein expression and pacemaking
      function. The analysis was carried out in tissue slices and single cells of the
      intercaval area, which includes the crista terminalis (CT), the SAN, and the
      septum interatrialis (SI). Immunolabeling, in situ hybridization, qRT-PCR
      analysis, and electrophysiological recordings identified the SAN as a region
      characterized by high HCN4 signal and current levels, while the expression in the
      CT and in the SI was either negligible or absent. Detailed analysis of the
      central SAN area showed that cells are predominantly distributed in islets
      interconnected by cell prolongations, and single-cell HCN4 labeling suggested
      sites of channel clustering. Our data indicate that in the rabbit SAN, HCN4
      proteins are major constituents of native f-channels, and their distribution
      matches closely the SAN as defined morphologically and electrophysiologically.
      Until recently, the SAN was identified as the region where Cx43 and atrial
      natriuretic peptide are not expressed; we propose here that expression of HCN4 is
      an appropriate tool to map and identify the cardiac SAN pacemaker region.

PMID- 19394342
TI  - Cardiac ankyrins in health and disease.
AB  - Ankyrins are critical components of ion channel and transporter signaling
      complexes in the cardiovascular system. Over the past 5 years, ankyrin
      dysfunction has been linked with abnormal ion channel and transporter membrane
      organization and fatal human arrhythmias. Loss-of-function variants in the
      ankyrin-B gene (ANK2) cause "ankyrin-B syndrome" (previously called type 4 long
      QT syndrome), manifested by a complex cardiac phenotype including ventricular
      arrhythmias and sudden cardiac death. More recently, dysfunction in the ankyrin-B
      based targeting pathway has been linked with a highly penetrant and severe form
      of human sinus node disease. Ankyrin-G (a second ankyrin gene product) is
      required for normal expression, membrane localization, and biophysical function
      of the primary cardiac voltage-gated sodium channel, Na(v)1.5. Loss of the
      ankyrin-G/Na(v)1.5 interaction is associated with human cardiac arrhythmia
      (Brugada syndrome). Finally, in the past year ankyrin dysfunction has been
      associated with more common arrhythmia and cardiovascular disease phenotypes.
      Specifically, large animal studies reveal striking remodeling of ankyrin-B and
      associated proteins following myocardial infarction. Additionally, the ANK2 locus
      has been linked with QT(c) interval variability in the general human population.
      Together, these findings identify a host of unanticipated and exciting roles for
      ankyrin polypeptides in cardiac function. More broadly, these findings illustrate
      the importance of local membrane organization for normal cardiac physiology.

PMID- 19394345
TI  - Probing muscle myosin motor action: x-ray (m3 and m6) interference measurements
      report motor domain not lever arm movement.
AB  - The key question in understanding how force and movement are produced in muscle
      concerns the nature of the cyclic interaction of myosin molecules with actin
      filaments. The lever arm of the globular head of each myosin molecule is thought
      in some way to swing axially on the actin-attached motor domain, thus propelling
      the actin filament past the myosin filament. Recent X-ray diffraction studies of
      vertebrate muscle, especially those involving the analysis of interference
      effects between myosin head arrays in the two halves of the thick filaments, have
      been claimed to prove that the lever arm moves at the same time as the sliding of
      actin and myosin filaments in response to muscle length or force steps. It was
      suggested that the sliding of myosin and actin filaments, the level of force
      produced and the lever arm angle are all directly coupled and that other models
      of lever arm movement will not fit the X-ray data. Here, we show that, in
      addition to interference across the A-band, which must be occurring, the observed
      meridional M3 and M6 X-ray intensity changes can all be explained very well by
      the changing diffraction effects during filament sliding caused by heads
      stereospecifically attached to actin moving axially relative to a population of
      detached or non-stereospecifically attached heads that remain fixed in position
      relative to the myosin filament backbone. Crucially, and contrary to previous
      interpretations, the X-ray interference results provide little direct information
      about the position of the myosin head lever arm; they are, in fact, reporting
      relative motor domain movements. The implications of the new interpretation are
      briefly assessed.

PMID- 19394344
TI  - Structures of glycinamide ribonucleotide transformylase (PurN) from Mycobacterium
      tuberculosis reveal a novel dimer with relevance to drug discovery.
AB  - Enzymes from the de novo purine biosynthetic pathway have been exploited for the
      development of anti-cancer drugs, and represent novel targets for anti-bacterial
      drug development. In Mycobacterium tuberculosis, the cause of tuberculosis, this
      pathway has been identified as essential for growth and survival. The structure
      of M. tuberculosis PurN (MtPurN) has been determined in complex with magnesium
      and iodide at 1.30 A resolution, and with cofactor analogue, 5
      methyltetrahydrofolate (5MTHF) at 2.2 A resolution. The structure shows a
      Rossmann-type fold that is very similar to the known structures of the human and
      E. coli PurN proteins. In contrast, MtPurN forms a dimer that is quite different
      from that formed by the Escherichia coli PurN, and which suggests a mechanism
      whereby communication could take place between the two active sites. Differences
      are seen in two active site loops and in the binding mode of the 5MTHF cofactor
      analogue between the two MtPurN molecules of the dimer. A binding site for halide
      ions is found in the dimer interface, and bound magnesium and iodide ions in the
      active site suggest sites that might be exploited in potential drug discovery
      strategies.

PMID- 19394346
TI  - The three-dimensional Structure of a mycobacterial DapD provides insights into
      DapD diversity and reveals unexpected particulars about the enzymatic mechanism.
AB  - The enzyme tetrahydrodipicolinate N-succinyltransferase (DapD) is part of the L
      lysine biosynthetic pathway. This pathway is crucial for the survival of the
      pathogen Mycobacterium tuberculosis (Mtb) and, consequently, the enzymes of the
      pathway are potential drug targets. We report here the crystal structures of Mtb
      DapD and of Mtb-DapD in complex with the co-factor succinyl-CoA (SCoA) at 2.15 A
      and 1.97 A resolution, respectively. Each subunit of the trimeric enzyme consists
      of three domains, of which the second, a left-handed, parallel beta-helix (LbetaH
      domain), is the common structural motif of enzymes belonging to the hexapeptide
      repeat superfamily. The trimeric quaternary structure is stabilized by Mg(2+) and
      Na(+) located on the 3-fold axis. The binary complex of Mtb-DapD and SCoA reveals
      the binding mode(s) of the co-factor and a possible covalent reaction
      intermediate. The N-terminal domain of Mtb-DapD exhibits a unique architecture,
      including an interior water-filled channel, which allows access to a magnesium
      ion located at the 3-fold symmetry axis.

PMID- 19394347
TI  - An ion-channel modulator from the saliva of the brown ear tick has a highly
      modified Kunitz/BPTI structure.
AB  - Ra-KLP, a 75 amino acid protein secreted by the salivary gland of the brown ear
      tick Rhipicephalus appendiculatus has a sequence resembling those of Kunitz/BPTI
      proteins. We report the detection, purification and characterization of the
      function of Ra-KLP. In addition, determination of the three-dimensional crystal
      structure of Ra-KLP at 1.6 A resolution using sulphur single-wavelength anomalous
      dispersion reveals that much of the loop structure of classical Kunitz domains,
      including the protruding protease-binding loop, has been replaced by beta
      strands. Even more unusually, the N-terminal portion of the polypeptide chain is
      pinned to the "Kunitz head" by two disulphide bridges not found in classical
      Kunitz/BPTI proteins. The disulphide bond pattern has been further altered by the
      loss of the bridge that normally stabilizes the protease-binding loop. Consistent
      with the conversion of this loop into a beta-strand, Ra-KLP shows no significant
      anti-protease activity; however, it activates maxiK channels in an in vitro
      system, suggesting a potential mechanism for regulating host blood supply during
      feeding.

PMID- 19394348
TI  - The pace of evolution across fitness valleys.
AB  - How fast does a population evolve from one fitness peak to another? We study the
      dynamics of evolving, asexually reproducing populations in which a certain number
      of mutations jointly confer a fitness advantage. We consider the time until a
      population has evolved from one fitness peak to another one with a higher
      fitness. The order of mutations can either be fixed or random. If the order of
      mutations is fixed, then the population follows a metaphorical ridge, a single
      path. If the order of mutations is arbitrary, then there are many ways to evolve
      to the higher fitness state. We address the time required for fixation in such
      scenarios and study how it is affected by the order of mutations, the population
      size, the fitness values and the mutation rate.

PMID- 19394349
TI  - The neural basis of visuomotor deficits in hemispatial neglect.
AB  - We have recently reported that patients with hemispatial neglect demonstrate
      increased terminal errors when performing delayed leftward reaches and that right
      brain damaged patients (irrespective of neglect) take longer to complete their
      movements [Rossit, S., Muir, K., Reeves, I., Duncan, G., Birschel, P., & Harvey,
      M. (2009). Immediate and delayed reaching in hemispatial neglect.
      Neuropsychologiaa 47, 1563-1573]. Here we conducted an initial voxel-based lesion
      symptom analysis to examine the neural basis of such deficits in 21 right-brain
      damaged subjects with 11 patients suffering from hemispatial neglect (2 more than
      in Rossit et al. [Rossit S., Muir K., Reeves I., Duncan, G., Birschel, P., &
      Harvey, M. (2009). Immediate and delayed reaching in hemispatial neglect.
      Neuropsychologia 47, 1563-1573] and 10 control patients without the condition. We
      found that the accuracy impairments in delayed leftward reaches were associated
      with damage to occipito-temporal areas. In contrast, the movement time slowing
      was related to more anterior lesions in the frontal lobe. These findings agree
      with the view that neglect affects actions thought to depend on the processing
      carried out by the ventral visual stream. In addition, we suggest that the timing
      impairments which are not neglect-specific maybe be driven by frontal structures.

PMID- 19394350
TI  - Effect of viscosity on learned satiation.
AB  - A higher viscosity of a food leads to a longer orosensory stimulation. This may
      facilitate the learned association between sensory signals and metabolic
      consequences. In the current study we investigated the effect of viscosity on
      learned satiation. In two intervention groups a low viscosity (LV) yogurt (n=24)
      and a high viscosity (HV) yogurt (n=22) was offered ad libitum for breakfast. In
      a learning period of 4 weeks, subjects consumed ad libitum a novel flavoured high
      energy density (HED) yogurt (150 kcal/100 g) or low energy density (LED) yogurt
      (50 kcal/100 g), with 10 exposures to each yogurt on alternate days. Over the
      repeated exposures, an interaction effect of exposure timeenergyviscosity on
      intake was seen (F(1,771)=4.12; p=0.04). In the HV intervention group a
      borderline significant interaction between exposure and energy density was
      observed (F(1,369)=3.61; p=0.06); after 10 exposures, the LED yogurt resulted in
      a 46+/-16 g higher intake compared with the HED yogurt. In the LV group, no
      significant interaction between exposure and energy density was seen
      (F(1,401)=1.04; p=0.31); after 10 exposures intake difference between the LED and
      HED yogurts was only 1.5+/-15 g. These results suggest that a higher viscosity
      facilitates learned satiation.

PMID- 19394352
TI  - Meal patterns of mice under systematically varying approach and unit costs for
      food in a closed economy.
AB  - Several field and experimental studies have investigated the behavioral economics
      of food intake. In the laboratory, operant behavior has been used to emulate cost
      and to generate demand functions that express the relationship between the price
      of food and amount consumed. There have been few such studies of motivated food
      seeking and intake in mice, and none has reported demand functions. Using albino
      (CD1) male mice, the present study compares food intake and meal patterns across
      a series of ratio cost schedules. The first experiment examined unit price. A
      closed economy was used in which the mice were in the test chambers for 23 h/day
      and earned all of their food via either a nose poke or lever press response under
      fixed (FUP5, FUP10, FUP25, FUP50), variable (VUP10, VUP20, VUP50), and
      progressive (PUP1.25, PUP1.5, PUP1.75) unit prices. Mice were run for 4 days at
      each cost. There were no consistent differences between the first and last day
      indicating that behavioral adjustments to schedule changes occurred rapidly. When
      averaged across all price schedules, mice in the nose poke group consumed more
      food than their lever press counterparts but the overall shapes of the demand
      curves did not differ between the two operant responses, with intake decreasing
      as price increased. The number of meals taken per day differed between two meal
      defining criteria that we applied, and there were some differences between the
      types of unit price schedule. In the second experiment, approach cost in the form
      of nose poke responses was required to activate a response device (lever) on
      which a fixed unit price for food was in force. These approach and unit costs
      were varied systematically. Meal number decreased, and meal size increased, with
      increasing approach cost even though nose pokes accounted for only a small
      fraction of the total response activity. Thus, meal patterns in mice are
      sensitive to approach cost while total amount consumed is more sensitive to unit
      price. These data are discussed in terms of the concept of foraging cost as
      either a unitary or a multidimensional variable.

PMID- 19394351
TI  - Prenatal stress programming of offspring feeding behavior and energy balance
      begins early in pregnancy.
AB  - To examine the long-term effects of stress experienced early in gestation on the
      programming of offspring feeding behaviors and energy balance, pregnant mice were
      exposed to stress during early pregnancy (days 1-7) and adult offspring examined
      on chow and high fat diets for long-term outcomes. Placental 11 beta
      hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) and insulin-like growth factor
      2 (IGF-2) expression was measured to determine the possible sex-specific
      contribution of prenatal stress (PNS) on fetal programming of embryo growth and
      development during early pregnancy. PNS mice showed a basal hyperphagia when on
      chow diet. Prenatal treatment differences were ameliorated when adult mice were
      on a high fat diet. Interestingly, PNS male mice also had significantly reduced
      body weights compared to control males on both chow and high fat diets. Body
      composition analyses revealed reduced body fat and increased lean mass in PNS
      mice on the high fat diet, but no differences were detected in plasma leptin or
      insulin-like growth factor 1 (IGF-1) levels. Mechanistic examination of gene
      expression in embryonic day 12 placentas found that early PNS was associated with
      increased IGF-2 expression and sex-dependent effects of stress on 11 beta-HSD2,
      supporting specific aspects of early pregnancy. These studies suggest that the
      long-term effects of stress during pregnancy on programming of feeding behavior
      and energy homeostasis begin much earlier in development than previously thought.

PMID- 19394353
TI  - Hippocampal lesions interfere with long-trace taste aversion conditioning.
AB  - This series of experiments investigated the effects of dorsal and ventral
      hippocampal lesions on taste aversion learning. Although damage to the
      hippocampus did not affect the acquisition of a taste aversion when the
      conditioning procedure used a relatively standard interval between taste and
      illness, both types of lesions produced a deficit in taste aversion when a long
      interval (3 h) was interposed between taste exposure and induction of illness. In
      the same subjects, trace fear conditioning was selectively impaired by ventral
      lesions, whereas water maze performance was selectively impaired by dorsal
      lesions. The results replicate past dissociations of dorsal and ventral
      hippocampal function, and also suggest that the hippocampus has a less
      differentiated role in long-trace taste aversion learning.

PMID- 19394354
TI  - Preparation and preliminary biological screening of cholic acid-juvenoid
      conjugates.
AB  - Steroidal compounds have been utilized as carriers and for modification of
      physico-chemical properties of model biologically active secondary alcohols -
      juvenoids. Juvenoids are juvenile hormone analogues - environmentally safe
      insecticides, possessing significant biological activity towards different
      arthropods groups in focus on insect pest species. Structure modification of
      juvenoids plays important role to control the rate of liberation and
      decomposition of juvenoid in digestive system and can also play important role in
      the mode of action towards selected insect. This study presents an approach to
      the synthesis of steroidal monomers and dimers carrying one and two molecules of
      a juvenoid in their structures. The prepared compounds were tested for their
      inhibition activity on reproduction of the blowfly Neobellieria (Sarcophaga)
      bullata. These steroid-juvenoid conjugates showed promising possibilities in
      synthesis of new unique biochemical insecticides. Preliminary biological test
      results of prepared compounds are presented.

PMID- 19394355
TI  - Chemical synthesis of 3beta-sulfooxy-7beta-hydroxy-24-nor-5-cholenoic acid: an
      internal standard for mass spectrometric analysis of the abnormal delta5-bile
      acids occurring in Niemann-Pick disease.
AB  - In Niemann-Pick disease, type C1, increased amounts of 3beta,7beta-dihydroxy-5
      cholenoic acid are reported to be present in urinary bile acids. The compound
      occurs as a tri-conjugate, sulfated at C-3, N-acetylglucosamidated at C-7, and N
      acylamidated with taurine or glycine at C-24. For sensitive LC-MS/MS analysis of
      this bile acid, a suitable internal standard is needed. We report here the
      synthesis of a satisfactory internal standard, 3beta-sulfooxy-7beta-hydroxy-24
      nor-5-cholenoic acid (as the disodium salt). The key reactions involved were (1)
      the so-called "second order" Beckmann rearrangement (one-carbon degradation at C
      24) of hyodeoxycholic acid (HDCA) 3,6-diformate with sodium nitrite in a mixture
      of trifluoroacetic anhydride and trifluoroacetic acid, (2) simultaneous inversion
      at C-3 and elimination at C-6 of the ditosylate derivatives of the resulting
      3alpha,6alpha-dihydroxy-24-nor-5beta-cholanoic acid with potassium acetate in
      aqueous N,N-dimethylformamide, and (3) regioselective sulfation at C-3 of an
      intermediary 3beta,7beta-dihydroxy-24-nor-Delta(5) derivative using sulfur
      trioxide-trimethylamine complex. Overall yield of the desired compound was 1.8%
      in 12 steps from HDCA.

PMID- 19394358
TI  - Clavulanic acid: a competitive inhibitor of beta-lactamases with novel anxiolytic
      like activity and minimal side effects.
AB  - Clavulanic acid is a member of the beta lactam family of antibiotics with little
      or no intrinsic antibacterial activity of its own; instead, it is used to enhance
      the activity of antibiotics by blocking bacterial beta-lactamases. Because
      clavulanic acid by itself is very safe, orally active and shows good brain
      penetrance, we sought to determine if it had any potential as a
      psychotherapeutic. Clavulanic acid was a tested across three mammalian species,
      hamsters, rats and cotton-top tamarin monkeys in a series of behavioral assays
      designed to screen for anxiolytic activity. In addition, several studies were
      done in rodents to compare the behavioral profile of clavulanic acid to the
      commonly prescribed benzodiazepines, particularly with respect to their unwanted
      side effects of motor depression, amnesia and neuroendocrine dysregulation. Our
      findings show that clavulanic acid is a highly potent anxiolytic in rodents
      without altering motor activity in the open field test, normal learning and
      memory in the Morris water maze, or normal stress hormone release. Orally
      administered clavulanic acid significantly reduces measures of anxiety in
      male/female pairs of cotton-top tamarins. In addition, male tamarins showed a
      highly significant increase in sexual arousal as measured by the number of penile
      erections. The fact clavulanic acid has anxiolytic activity in the tamarin holds
      the promise that this drug may be an effective therapeutic for the treatment of
      anxiety disorders in humans.

PMID- 19394356
TI  - Protective actions of ovarian hormones in the serotonin system of macaques.
AB  - The serotonin neurons of the dorsal and medial raphe nuclei project to all areas
      of the forebrain and play a key role in mood disorders. Hence, any loss or
      degeneration of serotonin neurons could have profound ramifications. In a monkey
      model of surgical menopause with hormone replacement and no neural injury, E and
      P decreased gene expression in the dorsal raphe nucleus of c-jun n-terminal
      kinase (JNK1) and kynurenine mono-oxygenase (KMO) that promote cell death. In
      concert, E and P increased gene expression of superoxide dismutase (SOD1), VEGF,
      and caspase inhibitory proteins that promote cellular resilience in the dorsal
      raphe nucleus. Subsequently, we showed that ovarian steroids inhibit pivotal
      genes in the caspase-dependent and caspase-independent pathways in laser-captured
      serotonin neurons including apoptosis activating factor (Apaf1), apoptosis
      inducing factor (AIF) and second mitochondria-derived activator of caspases
      (Smac/Diablo). SOD1 was also increased specifically in laser-captured serotonin
      neurons. Examination of protein expression in the dorsal raphe block revealed
      that JNK1, phosphoJNK1, AIF and the translocation of AIF from the mitochondria to
      the nucleus decreased with hormone therapy, whereas pivotal execution proteins in
      the caspase pathway were unchanged. In addition, cyclins A, B, D1 and E were
      inhibited, which would prevent re-entry into the cell cycle and catastrophic
      death. These data indicated that in the absence of gross injury to the midbrain,
      ovarian steroids inhibit the caspase-independent pathway and cell cycle
      initiation in serotonin neurons. To determine if these molecular actions
      prevented cellular vulnerability or death, we examined DNA fragmentation in the
      dorsal raphe nucleus with the TUNEL assay (terminal deoxynucleotidyl transferase
      nick end labeling). Ovarian steroids significantly decreased the number of TUNEL
      positive cells in the dorsal raphe. Moreover, TUNEL staining prominently
      colocalized with TPH immunostaining, a marker for serotonin neurons. In summary,
      ovarian steroids increase the cellular resilience of serotonin neurons and may
      prevent serotonin neuron death in women facing decades of life after menopause.
      The survival of serotonin neurons would support cognition and mental health.

PMID- 19394360
TI  - A minimally invasive approach to long-term head fixation in behaving nonhuman
      primates.
AB  - We have designed a device for long-term head fixation for use in behaving
      nonhuman primates that is robust yet minimally invasive and simple to use. This
      device is a modified version of the halo system that is used in humans for
      cervical traction and stabilization after spinal column injuries. This device
      consists of an aluminum halo with four titanium skull pins offset from the halo
      by aluminum posts. The titanium pins insert onto small segments of cranially
      reinforcing titanium plate, which are attached to the skull with titanium cortex
      screws. The surgery involves four scalp incisions, placement of the reinforcing
      plates, insertion of the pins for attachment of the halo, and incision closure.
      After the halo is attached, the animal's head can be fixed to a primate chair
      using a custom-built attachment arm that provides three degrees of adjustability
      for proper positioning during behavioral tasks. We have installed this device on
      two Macaque monkeys weighing 7 and 10kg. The halos have been in place on these
      animals for up to 8 months without signs of discomfort or loss of fixation. Using
      this method of head fixation, we have been able to track the animals' eye
      positions with an accuracy of less than two visual degrees while they perform
      behavioral tasks.

PMID- 19394361
TI  - A new EMG frequency-based fatigue threshold test.
AB  - Theoretically, the critical torque (CT) and electromyographic mean power
      frequency fatigue threshold (EMG MPF(FT)) describe the maximal non-fatiguing
      isometric torque level. PURPOSE: The purposes of this study were two-fold: (1) to
      determine if the mathematical model for estimating the EMG fatigue threshold
      (EMG(FT)) from the amplitude of the EMG signal was applicable to the frequency
      domain of the EMG signal to estimate a new fatigue threshold called the EMG
      MPF(FT); and (2) to compare the torque level derived from the CT test to that of
      the EMG MPF(FT) test for the vastus lateralis (VL) muscle during isometric muscle
      actions of the leg extensors. METHODS: Nine adults (4 men and 5 women; mean+/-SD
      age=21.6+/-1.2 yr) performed three or four continuous, fatiguing, isometric
      muscle actions of the leg extensors at 30, 45, 60, and 75% of maximum voluntary
      isometric contraction (MVIC) to determine the time to exhaustion (T(lim)) values.
      The slope coefficient of the linear relationship between total isometric "work"
      (W(lim) in Nms=TorquexT(lim)) and T(lim) was defined as the CT. Surface EMG
      signals were recorded from the vastus lateralis (VL) muscle during each fatiguing
      isometric muscle action. The EMG MPF(FT) was defined as the y-intercept of the
      isometric torque versus slope coefficient (EMG MPF versus time) plot. RESULTS:
      There were no significant differences between CT (19.7+/-5.8%MVIC) and EMG
      MPF(FT) (21.4+/-8.7%MVIC). CONCLUSION: These findings provided indirect
      validation of the EMG MPF(FT) test.

PMID- 19394359
TI  - Mitochondrial structural and functional dynamics in Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal, dominantly inherited neurodegenerative
      disorder, characterized by chorea, involuntary movements, and cognitive
      impairments. Tremendous progress has been made since the discovery of HD gene in
      1993, in terms of developing animal models to study the disease process,
      unraveling the expression and function of wild-type and mutant huntingtin (Htt)
      proteins in the central and peripheral nervous systems, and understanding
      expanded CAG repeat containing mutant Htt protein interactions with CNS proteins
      in the disease process. HD progression has been found to involve several
      pathomechanisms, including expanded CAG repeat protein interaction with other CNS
      proteins, transcriptional dysregulation, calcium dyshomeostasis, abnormal vesicle
      trafficking, and defective mitochondrial bioenergetics. Recent studies have found
      that mutant Htt is associated with mitochondria and causes mitochondrial
      structural changes, decreases mitochondrial trafficking, and impairs
      mitochondrial dynamics in the neurons affected by HD. This article discusses
      recent developments in HD research, with a particular focus on intracellular and
      intramitochondrial calcium influx, mitochondrial DNA defects, and mitochondrial
      structural and functional abnormalities in HD development and progression.
      Further, this article outlines the current status of mitochondrial therapeutics
      with a special reference to Dimebon.

PMID- 19394362
TI  - Post-processing of auditory steady-state responses to correct spectral leakage.
AB  - Auditory steady-state responses (ASSRs) are electrical manifestations of brain
      due to high rate sound stimulation. These evoked responses can be used to assess
      the hearing capabilities of a subject in an objective, automatic fashion.
      Usually, the detection protocol is accomplished by frequency-domain techniques,
      such as magnitude-squared coherence, whose estimation is based on the fast
      Fourier transform (FFT) of several data segments. In practice, the FFT-based
      spectrum may spread out the energy of a given frequency to its side bins and this
      escape of energy in the spectrum is called spectral leakage. The distortion of
      the spectrum due to leakage may severely compromise statistical significance of
      objective detection. This work presents an offline, a posteriori method for
      spectral leakage minimization in the frequency-domain analysis of ASSRs using
      coherent sampling criterion and interpolation in time. The technique was applied
      to the local field potentials of 10 Wistar rats and the results, together with
      those from simulated data, indicate that a leakage-free analysis of ASSRs is
      possible for any dataset if the methods showed in this paper were followed.

PMID- 19394357
TI  - Combination treatment with progesterone and vitamin D hormone may be more
      effective than monotherapy for nervous system injury and disease.
AB  - More than two decades of pre-clinical research and two recent clinical trials
      have shown that progesterone (PROG) and its metabolites exert beneficial effects
      after traumatic brain injury (TBI) through a number of metabolic and
      physiological pathways that can reduce damage in many different tissues and organ
      systems. Emerging data on 1,25-dihydroxyvitamin D(3) (VDH), itself a steroid
      hormone, have begun to provide evidence that, like PROG, it too is
      neuroprotective, although some of its actions may involve different pathways.
      Both agents have high safety profiles, act on many different injury and
      pathological mechanisms, and are clinically relevant, easy to administer, and
      inexpensive. Furthermore, vitamin D deficiency is prevalent in a large segment of
      the population, especially the elderly and institutionalized, and can
      significantly affect recovery after CNS injury. The combination of PROG and VDH
      in pre-clinical and clinical studies is a novel and compelling approach to TBI
      treatment.

PMID- 19394363
TI  - New approaches to eliminating common-noise artifacts in recordings from
      intracortical microelectrode arrays: inter-electrode correlation and virtual
      referencing.
AB  - Intracortical microelectrode arrays record multi-unit extracellular activity for
      neurophysiology studies and for brain-machine interface applications. The common
      first step is neural spike-detection; a process complicated by common-noise
      signals from motion artifacts, electromyographic activity, and electric field
      pickup, especially in awake/behaving subjects. Often common-noise spikes are very
      similar to neural spikes in their magnitude, spectral, and temporal features.
      Provided sufficient spacing exists between electrodes of the array, a local
      neural spike is rarely recorded on multiple electrodes simultaneously. This is
      not true for distant common-noise sources. Two new techniques compatible with
      standard spike-detection schemes are introduced and evaluated. The first method,
      virtual referencing (VR), takes the average recording from all functional
      electrodes in the array (represents the signal from a virtual-electrode at the
      array's center) and subtracts it from the test electrode signal. The second
      method, inter-electrode correlation (IEC), computes a correlation coefficient
      between threshold exceeding candidate spike segments on the test electrode and
      concurrent segments from remaining electrodes. When sufficient correlation is
      detected, the candidate spike is rejected as originating from a distant common
      noise source. The performance of these algorithms was compared with standard
      thresholding and differential referencing approaches using neural recordings from
      un-anaesthetized rats. By evaluating characteristics of mean-spike waveforms
      generated by each method under different levels of common-noise, it was found
      that IEC consistently offered the most robust means of neural spike-detection.
      Furthermore, IEC's rejection of supra-threshold events not likely originating
      from local neurons significantly reduces data handling for downstream spike
      sorting and processing operations.

PMID- 19394364
TI  - Mouse monoclonal autoantibodies penetrate mouse macrophage cells and stimulate NF
      kappaB activation and TNF-alpha release.
AB  - Autoantibodies against double-stranded DNA (dsDNA) are found in the serum of
      systemic lupus erythematosus (SLE) patients. However, the mechanism by which anti
      dsDNA antibodies (Abs) contribute to the pathogenesis of SLE is not yet fully
      understood. In this study, we investigated four anti-dsDNA mouse monoclonal
      autoantibodies that share positively charged amino acids (including arginines) in
      their complementarity determining regions for their ability to penetrate RAW264.7
      macrophage cells, activate NF-kappaB and stimulate TNF-alpha production. All four
      antibodies penetrated into macrophage cells and increased the level of
      extracellular TNF-alpha; two also activated NF-kappaB. The fact that two of four
      cell-penetrating anti-dsDNA mAbs induced both NF-kappaB activation and TNF-alpha
      production in macrophages suggests that at least some autoantibodies against
      dsDNA may play a role in the pathogenesis of SLE by penetrating into macrophage
      cells and nuclei, and subsequently inducing the pro-inflammatory cytokine, TNF
      alpha, by binding to the NF-kappaB gene and stimulating its transcriptional
      activity.

PMID- 19394365
TI  - Verapamil enhances acute stress or glucocorticoid-induced deficits in retrieval
      of long-term memory in rats.
AB  - This study was designed to investigate an interaction between acute restraint
      stress and corticosterone with verapamil, a blocker of L-type voltage-dependent
      calcium (VDC) channels on retrieval of long-term memory. Young adult male rats
      were trained in one trial inhibitory avoidance task (0.5 mA, 3 s footshock). On
      retention test given 48 h after training, the latency to re-enter dark
      compartment of the apparatus was recorded. In Experiment 1, verapamil
      pretreatment (5, 10, or 20 mg/kg) enhanced the impairing effects of acute stress
      (which was applied for 10 min in a Plexiglass tube 30 min before the retention
      test) on memory retrieval. The applied stress increased circulating
      corticosterone levels as assessed immediately after the retention test,
      indicating that stress-induced impairment of memory retrieval is mediated, in
      part, by increased plasma levels of glucocorticoids. Verapamil did not change
      this response. In Experiment 2, pretreatment of an intermediate dose of verapamil
      also enhanced corticosterone-induced impairment of memory retrieval. In
      Experiments 3 and 4, acute stress or corticosterone did not change motor activity
      with or without prior treatment of verapamil, suggesting that stress or
      glucocorticoid-induced impairment of memory retrieval is not due to any gross
      disturbances in motor performance of animals. These findings indicate that
      blockade of L-type VDC channels enhances stress or glucocorticoid-induced
      impairment of memory retrieval, and provide evidence for the existence of an
      interaction between glucocorticoids and L-type VDC channels on memory retrieval.

PMID- 19394366
TI  - Differential effects of repeated long and brief maternal separation on behaviour
      and neuroendocrine parameters in Wistar dams.
AB  - Repeated, prolonged maternal separation has been suggested to model the
      development of a depression-like syndrome in rats. The long separations from the
      pups have been proposed to be stressful for the dams, which in turn could mediate
      the changes seen in adult offspring. In the present study we investigated whether
      prolonged maternal separation really is stressful for rat dams by studying
      parameters known to be affected by long-term stress such as spontaneous motor
      activity, anxiety-like behaviour, adrenal gland weight and plasma corticosterone
      levels. Dams were separated from their litter for either 4 h (MS240) or 15 min
      (MS15) on eight random days during postnatal day 1-14, or left undisturbed
      (animal facility reared, AFR). After weaning MS240 dams showed decreased
      peripheral activity and habituated slower in horizontal activity. On the
      contrary, MS15 dams showed more peripheral activity and less rearing activity
      compared to both AFR and MS240 dams when habituated to the testing apparatus,
      suggesting that MS15 dams are more anxious. The adrenal glands from MS15 dams
      weighed significantly less and plasma corticosterone levels were significantly
      higher compared to AFR and MS240 dams. These results suggest that repeated brief
      maternal separations from pups could be stressful for rat mothers, whereas
      prolonged separations are not. Since these results are in contrast to the current
      notion that the short separation procedure may be considered as a safe milieu,
      whereas the prolonged separations have been suggested to be stressful for both
      dams and pups, further studies in this field are warranted.

PMID- 19394367
TI  - Male but not female Wistar rats show increased anxiety-like behaviour in response
      to bright light in the defensive withdrawal test.
AB  - The defensive withdrawal test (DWT) is used to model anxiety-like behaviour in
      rats. The aim of this study was to investigate whether an aversive stimulus,
      bright light, affects the behaviour in this test. Additionally, the effect of
      habituation to the apparatus was studied. Both male and female Wistar rats were
      used to study whether sex differences exist in the DWT, as reported for other
      tests of anxiety. On day 1 half of the rats were tested under low light and half
      under bright light. Two to seven days after trial one the same rats were
      repeatedly tested under the same light condition for five consecutive days. The
      male rats showed a higher degree of anxiety-like behaviour when tested under
      bright light than under low light. In contrast, the behaviour of the female rats
      was not affected by changes in illumination. Male rats also exhibited elevated
      anxiety-like behaviour compared to female rats under bright light, whereas under
      low light conditions no sex difference was seen. Males in low light habituated
      much faster than males tested under bright light, whereas in females there was
      little difference in habituation between low and bright light. In summary, we
      found that bright light is aversive for male but not female Wistar rats in the
      DWT. Whether this is due to sex differences in light sensitivity or if females
      respond with a different behavioural strategy in response to bright light, which
      could not be detected in the DWT, remains to be elucidated.

PMID- 19394368
TI  - Neural responses of rats in the forced swimming test: [F-18]FDG micro PET study.
AB  - The forced swimming test (FST) is a widely used tool in the assessment of
      behavioral despair and prediction of response to antidepressants. However, the
      neural mechanisms underlying behavioral changes between pretest and test sessions
      of the FST remain unclear. In this study, we investigated changes in rat brain
      activity during the FST using [F-18]Fluorodeoxyglucose micro PET. In both pretest
      and test sessions, the activity of the cerebellum and striatum increased, whereas
      significant deactivation was observed in the hippocampus, inferior colliculus,
      orbital cortex, and insula. The periaqueductal gray (PAG) region activated
      markedly in the pretest session, but did not activate in the test session. There
      was a significant increase in immobility and a decrease in climbing during the
      behavioral analysis test session. These results suggest that the PAG region may
      play an important role in the modulation of FST coping strategies subsequent to
      failure of the escape response during the pretest session.

PMID- 19394369
TI  - Recent advances in peptide probe-based biosensors for detection of infectious
      agents.
AB  - Recent biological terrorism threats and outbreaks of microbial pathogens clearly
      emphasize the need for biosensors that can quickly and accurately identify
      infectious agents. The majority of rapid biosensors generate detectable signals
      when a molecular probe in the detector interacts with an analyte of interest.
      Analytes may be whole bacterial or fungal cells, virus particles, or specific
      molecules, such as chemicals or protein toxins, produced by the infectious agent.
      Peptides and nucleic acids are most commonly used as probes in biosensors because
      of their versatility in forming various tertiary structures. The interaction
      between the probe and the analyte can be detected by various sensor platforms,
      including quartz crystal microbalances, surface acoustical waves, surface plasmon
      resonance, amperometrics, and magnetoelastics. The field of biosensors is
      constantly evolving to develop devices that have higher sensitivity and
      specificity, and are smaller, portable, and cost-effective. This mini review
      discusses recent advances in peptide-dependent rapid biosensors and their
      applications as well as relative advantages and disadvantages of each technology.

PMID- 19394370
TI  - A game with many players: control of gdh transcription in Corynebacterium
      glutamicum.
AB  - Glutamate dehydrogenase is a central enzyme connecting nitrogen and carbon
      metabolism via its precursors ammonium and oxoglutarate and its product
      glutamate. In Corynebacterium glutamicum glutamate dehydrogenase is especially
      important, since it is a key enzyme for the biotechnological production of the
      flavour enhancer L-glutamate. In this study, the regulation of gdh transcription
      was investigated. While originally described as a constitutively expressed gene,
      we could show that gdh transcription is highly variable depending on
      environmental conditions. Regulation of the gdh gene by the C. glutamicum
      nitrogen control protein AmtR was analyzed in detail in this study.

PMID- 19394371
TI  - A novel budgerigar-adenovirus belonging to group II avian adenovirus of
      Siadenovirus.
AB  - Five budgerigars in the same breeding facility died or showed ruffled feathers.
      To determine the cause, five dead or euthanized budgerigars were examined.
      Splenomegaly was observed at necropsy in all birds examined. Histopathology of
      the spleen revealed a slight-to-moderate deletion of lymphocytes and increase of
      macrophages. Concurrent congestions in several tissues such as liver, lung,
      kidney, and/or brain and basophilic intranuclear inclusion bodies in the
      epithelial cells of renal tubules were found in all the birds examined.
      Psittacine adenoviral DNA was detected in the kidney of one of the five
      budgerigars by PCR. Sequencing and phylogenetic analysis of the hexon gene
      revealed that the adenovirus gene detected in the budgerigar was derived from an
      unknown adenovirus belonging to the genus Siadenovirus. Using a new pair of
      primers based on the obtained sequence, we confirmed the presence of the newly
      found adenovirus in all five birds. The newly found unknown adenovirus is
      designated as Budgerigar Adenovirus 1.

PMID- 19394372
TI  - Soybean cultivar resistant to Mungbean Yellow Mosaic India Virus infection
      induces viral RNA degradation earlier than the susceptible cultivar.
AB  - Yellow mosaic disease caused by whitefly-transmitted bipartite Geminiviruses is
      one of the major constraints on productivity of a number of pulse crops. We have
      cloned the bipartite genome of Mungbean Yellow Mosaic India Virus isolated from
      infected Soybean. We report here that agroinfection of Soybean seedlings with a
      single uncut recombinant binary plasmid containing tandem dimers of both DNA A
      and DNA B resulted in 100% infectivity in susceptible varieties. To understand
      the mechanism of natural resistance in a Soybean variety, we compared the
      abundance of the viral RNAs in a resistant and a susceptible variety at the early
      time points after agroinfection. Whilst the resistant variety displayed synthesis
      but rapid degradation of the early viral RNAs; the degradation in the susceptible
      variety was delayed resulting in accumulation of those transcripts later in
      infection. Accumulation of the late viral transcripts and DNA replication were
      detectable only in the susceptible variety. This indicates that rapid degradation
      of the early viral transcripts, possibly through siRNA mechanism, is one of the
      probable mechanisms of natural resistance against geminivirus.

PMID- 19394373
TI  - In vivo gene regulation using tetracycline-regulatable systems.
AB  - Numerous preclinical studies have demonstrated the efficacy of viral gene
      delivery vectors, and recent clinical trials have shown promising results.
      However, the tight control of transgene expression is likely to be required for
      therapeutic applications and in some instances, for safety reasons. For this
      purpose, several ligand-dependent transcription regulatory systems have been
      developed. Among these, the tetracycline-regulatable system is by far the most
      frequently used and the most advanced towards gene therapy trials. This review
      will focus on this system and will describe the most recent progress in the
      regulation of transgene expression in various organs, including the muscle, the
      retina and the brain. Since the development of an immune response to the
      transactivator was observed following gene transfer in the muscle of nonhuman
      primate, focus will be therefore, given on the immune response to transgene
      products of the tetracycline inducible promoter.

PMID- 19394374
TI  - Conditional RNAi: towards a silent gene therapy.
AB  - RNA interference (RNAi) has the potential to permit the downregulation of
      virtually any gene. While transgenic RNAi enables stable propagation of the
      resulting phenotype to progeny, the dominant nature of RNAi limits its use to
      applications where the continued suppression of gene expression does not disturb
      normal cell functioning. This is of particular importance when the target gene
      product is essential for cell survival, development or differentiation. It is
      therefore desirable that knockdown be externally regulatable. This review is
      aimed at providing an overview of the approaches for conditional RNAi in
      mammalian systems, with a special mention of studies employing these approaches
      to target therapeutically/biologically relevant molecules, their advantages and
      disadvantages, and a pointer towards approaches best suited for RNAi-based gene
      therapy.

PMID- 19394375
TI  - Zinc-finger-based artificial transcription factors and their applications.
AB  - Artificial transcription factors (ATFs) are potentially a powerful molecular tool
      to modulate endogenous target gene expression in living cells and organisms. To
      date, many DNA-binding molecules have been developed as the DNA-binding domains
      for ATFs. Among them, ATFs comprising Cys(2)His(2)-type zinc-finger proteins
      (ZFPs) as the DNA-binding domain have been extensively explored. The zinc-finger
      based ATFs specifically recognize targeting sites in chromosomes and effectively
      up- and downregulate expression of their target genes not only in vitro, but also
      in vivo. In this review, after briefly introducing Cys(2)His(2)-type ZFPs, I will
      review the studies of endogenous human gene regulation by zinc-finger-based ATFs
      and other applications as well.

PMID- 19394376
TI  - Targeting cancer by transcriptional control in cancer gene therapy and viral
      oncolysis.
AB  - Cancer-specificity is the key requirement for a drug or treatment regimen to be
      effective against malignant disease--and has rarely been achieved adequately to
      date. Therefore, targeting strategies need to be implemented for future therapies
      to ensure efficient activity at the site of patients' tumors or metastases
      without causing intolerable side-effects. Gene therapy and viral oncolysis
      represent treatment modalities that offer unique opportunities for tumor
      targeting. This is because both the transfer of genes with anti-cancer activity
      and viral replication-induced cell killing, respectively, facilitate the
      incorporation of multiple mechanisms restricting their activity to cancer. To
      this end, cellular mechanisms of gene regulation have been successfully exploited
      to direct therapeutic gene expression and viral cell lysis to cancer cells. Here,
      transcriptional targeting has been the role model and most widely investigated.
      This approach exploits cellular gene regulatory elements that mediate cell type
      specific transcription to restrict the expression of therapeutic genes or
      essential viral genes, ideally to cancer cells. In this review, we first discuss
      the rationale for such promoter targeting and its limitations. We then give an
      overview how tissue-/tumor-specific promoters are being identified and
      characterized. Strategies to apply and optimize such promoters for the
      engineering of targeted viral gene transfer vectors and oncolytic viruses-with
      respect to promoter size, selectivity and activity in the context of viral
      genomes-are described. Finally, we discuss in more detail individual examples for
      transcriptionally targeted virus drugs. First highlighting oncolytic viruses
      targeted by prostate-specific promoters and by the telomerase promoter as
      representatives of tissue-targeted and pan-cancer-specific virus drugs
      respectively, and secondly recent developments of the last two years.

PMID- 19394377
TI  - Glucose-responsive gene expression system for gene therapy.
AB  - Regulation of gene expression by glucose is an important mechanism for mammals in
      adapting to their nutritional environment. Glucose, the primary fuel for most
      cells, modulates gene expression that is crucial in the cellular adaptation to
      glycemic variation. Transcription of the genes for insulin and glycolytic and
      lipogenic enzymes is stimulated by glucose in pancreatic beta-cells and liver.
      Recent findings further support the key role of the carbohydrate-responsive
      element binding protein in the regulation of glycolytic and lipogenic genes by
      glucose and dietary carbohydrates. Herein, we review the transcriptional
      regulation of glucose-responsive genes, and recent advances in the gene therapy
      using glucose-responsive gene expression for diabetes.

PMID- 19394378
TI  - Heat-responsive gene expression for gene therapy.
AB  - Therapy-inducible vectors are useful for conditional expression of therapeutic
      genes in gene therapy, which is based on the control of gene expression by
      conventional treatment modalities. By this approach, combination of chemotherapy,
      radiation or hyperthermia with gene therapy can result in considerable, additive
      or synergistic improvement of therapeutic efficacy. This concept has been
      successfully tested in particular for gene therapy of cancer. The identification
      of efficient heat-responsive gene promoters provided the rationale for heat
      regulated gene therapy. The objective of this review is to provide insights into
      the cellular mechanisms of heat-shock response, as prerequisite for therapeutic
      actions of hyperthermia and into the field of heat-responsive gene therapy.
      Furthermore, the major strategies of heat-responsive gene therapy systems in
      particular for cancer treatment are summarized. The developments for heat
      responsive vector systems for in vitro and in vivo approaches are discussed. This
      review will provide an overview for this gene therapy strategy and its potential
      for multimodal therapeutic concepts in the clinic.

PMID- 19394379
TI  - Hypoxia-specific gene expression for ischemic disease gene therapy.
AB  - Gene therapy for ischemic diseases has been developed with various growth factors
      and anti-apoptotic genes. However, non-specific expression of therapeutic genes
      may induce deleterious side effects such as tumor formation. Hypoxia-specific
      regulatory systems can be used to regulate transgene expression in hypoxic
      tissues, in which gene expression is induced in ischemic tissues, but reduced in
      normal tissues by transcriptional, translational or post-translational
      regulation. Since hypoxia-inducible factor 1 (HIF-1) activates transcription of
      genes in hypoxic tissues, it can play an important role in the prevention of
      myocardial and cerebral ischemia. Hypoxia-specific promoters including HIF-1
      binding sites have been used for transcriptional regulation of therapeutic genes.
      Also, hypoxia-specific untranslated regions (UTRs) and oxygen dependent
      degradation (ODD) domains have been investigated for translational and post
      translational regulations, respectively. Hypoxia-specific gene expression systems
      have been applied to various ischemic disease models, including ischemic
      myocardium, stroke, and injured spinal cord. This review examines the current
      status and future challenges of hypoxia-specific systems for safe and effective
      gene therapy of ischemic diseases.

PMID- 19394380
TI  - Transcriptional targeting to brain cells: Engineering cell type-specific promoter
      containing cassettes for enhanced transgene expression.
AB  - Transcriptional targeting using a mammalian cellular promoter to restrict
      transgene expression to target cells is often desirable for gene therapy. This
      strategy is, however, hindered by relatively weak activity of some cellular
      promoters, which may lead to low levels of gene expression, thus declining
      therapeutic efficacy. Here we outline the advances accomplished in the area of
      transcriptional targeting to brain cells, with a particular focus on engineering
      gene cassettes to augment cell type-specific expression. Among the effective
      approaches that improve gene expression while retaining promoter specificity are
      promoter engineering to change authentic sequences of a cellular promoter and the
      combined use of a native cellular promoter and other cis-acting elements. Success
      in achieving high level and sustained transgene expression only in the cell types
      of interest would be of importance in allowing gene therapy to have its impact on
      patient treatment.

PMID- 19394382
TI  - Hypothalamic melanocortin signaling and leptin resistance--perspective of
      therapeutic application for obesity-diabetes syndrome.
AB  - The adipocyte-derived hormone, leptin controls feeding behavior, augments fatty
      acid beta-oxidation in the skeletal muscle, attenuates insulin secretion but
      enhances whole body insulin sensitivity and glucose disposal, thereby serving as
      a promising therapeutic candidate for the treatment of insulin resistance and
      dyslipidemia. Along with other researchers, we demonstrated the clinical efficacy
      and safety of leptin in the treatment of diabetes and dyslipidemia for patients
      with generalized lipodystrophy. However, the clinical application of leptin has
      been hampered by the notion that leptin does not fully exert its metabolic
      effects in human obesity and diet-induced obese rodents. We found that the
      activity of skeletal muscle AMP-activated protein kinase (AMPK) parallels
      hypothalamic leptin sensitivity and metabolic phenotype in transgenic mice
      overexpressing leptin. Our data indicate that the activation of skeletal muscle
      AMPK is mediated by the hypothalamic melanocortin pathway. In fact,
      intracerebroventricular administration of melanocortin agonist, MT-II in mice
      robustly overcomes high-fat diet-induced leptin resistance and ameliorates fuel
      dyshomeostasis and hyperphagia, with a concomitant recovery of AMPK activity in
      skeletal muscle. Conversely, AMPK/ACC phosphorylation by leptin was abrogated by
      the co-administration of melanocortin antagonist, SHU9119 and in the KKA(y) mice,
      which centrally express endogenous melanocortin antagonist. Importantly, high-fat
      diet-induced attenuation of AMPK/ACC phosphorylation in leptin-overexpressing
      transgenic mice was not reversed by central leptin per se, but was markedly
      recovered by MT-II. Our data provide evidence for the critical role of the
      central melanocortin system in leptin-skeletal muscle AMPK axis, and highlight
      the system as a therapeutic target for leptin insuffciency in obese humans.

PMID- 19394381
TI  - Psychological distress and dietary patterns in eight post-Soviet republics.
AB  - The purpose of this study is to examine the relationship between psychological
      distress and dietary consumption patterns in the former Soviet Union. Data are
      cross-sectional and were collected in 2001 from a large representative sample (n
      = 18,428) of respondents age 18 years and over in eight former Soviet republics.
      Sociodemographic covariates and psychological distress predictors were analyzed
      using ordinal logistic regression models to estimate multivariate correlations
      with the frequency of meat, fish, vegetable, fruit, and animal fat consumption
      among men and women in these eight regions. Results show that psychological
      distress exhibits statistically significant, negative associations with all
      dietary consumption indicators for both men and women. Social class predictors
      display consistent positive correlations with food consumption outcomes,
      emphasizing the potential importance of this concept in the dynamic relationship
      between diet and psychological distress. Higher reported levels of psychological
      distress are associated with the less frequent consumption of all types of food
      products in this analysis. Several possible interpretations are discussed, and we
      explore the probable multidimensional theoretical mechanisms that can help
      explain the complex relationships among distress, food insecurity, and dietary
      patterns in these eight republics of the former USSR. The general and practical
      significance of these findings is also discussed, along with suggested directions
      for future research and potential dietary intervention strategies.

PMID- 19394383
TI  - Comparison of independent and combined chronic anti-obese effects of NPY Y2
      receptor agonist, PYY(3-36), and NPY Y5 receptor antagonist in diet-induced obese
      mice.
AB  - Neuropeptide Y (NPY) and its family of peptides are thought to have a major role
      in the physiological control of energy homeostasis. Among five NPY receptors
      described, stimulation of the Y2 receptor (Y2R) or inhibition of the Y5 receptor
      (Y5R) has recently been shown to produce weight-lowering effects in obese
      rodents. The present study examined and compared the effects of a Y2R agonist,
      PYY(3-36), and a Y5R antagonist, alone and in combination, on food intake and
      body weight in diet-induced obese (DIO) mice. Acute intraperitoneal injection of
      PYY(3-36) dose-dependently reduced spontaneous feeding in lean and DIO mice. In
      contrast, acute oral administration of the Y5R antagonist had no effect on
      spontaneous feeding or the anorexigenic effects of PYY(3-36). In a chronic study,
      subcutaneous infusion of PYY(3-36) (1 mg/kg/day for 14 days) significantly
      reduced food intake and body weight in DIO mice. The Y5R antagonist (10 mg/kg/day
      for 14 days, orally) reduced body weight to the same extent as PYY(3-36) without
      a significant feeding reduction. Combined administration of PYY(3-36) and the Y5R
      antagonist resulted in a greater body weight reduction than treatment with either
      agent alone. The combined effects on food intake, body weight, and adiposity are
      almost the same as a hypothetical sum of the effects of each drug alone. These
      results illustrate that the combination of a Y2R agonist, PYY(3-36), and a Y5R
      antagonist resulted in additive effects on body weight and adiposity in DIO mice,
      suggesting that Y2R stimulation signal and Y5R blockade signal act by distinct
      pathways.

PMID- 19394384
TI  - Role of TRPC1 and NF-kappaB in mediating angiotensin II-induced Ca2+ entry and
      endothelial hyperpermeability.
AB  - Endothelial dysfunction is associated with cardiovascular diseases. The Ca(2+)
      influx occurring via activation of plasmalemma Ca(2+) channels was shown to be
      critical in signaling the increase in endothelial permeability in response to a
      variety of permeability-increasing mediators. It has been reported that
      angiotensin II (AngII) could induce Ca(2+) signaling in some cells, and transient
      receptor potential canonical 1 (TRPC1) had an important role in this process. The
      objective of this study was to examine the mechanism of AngII-induced Ca(2+)
      entry and vascular endothelial hyperpermeability. Human umbilical vein
      endothelial cells (HUVECs) exposed to AngII exhibited dose-dependent increase in
      [Ca(2+)]i and endothelial permeability. Quantitative real-time RT-PCR and Western
      blotting showed that the level of TRPC1 expression had increased significantly at
      12h and at 24h after treatment of HUEVCs with AngII. The expression of p65 was
      suppressed using an RNAi strategy. The results showed that the NF-kappaB
      signaling pathway and type-1 receptor of AngII was involved in AngII-induced
      TRPC1 upregulation. Moreover, knockdown of TRPC1 and NF-kappaB expression
      attenuates AngII-induced [Ca(2+)]i and endothelial permeability. NF-kappaB and
      TRPC1 have critical roles in AngII-induced Ca(2+) entry and endothelial
      permeability.

PMID- 19394386
TI  - Genetic association analysis of NRG1 with methamphetamine-induced psychosis in a
      Japanese population.
AB  - The neuregulin 1 gene (NRG1) has been identified as a candidate gene for
      schizophrenia in a linkage study in the Icelandic population. Recent evidence
      also suggested that it might be related to the neurodevelopmental hypothesis and
      glutamate hypothesis for schizophrenia. Because the symptomatology of
      methamphetamine (METH) use disorder with accompanying psychosis is similar to
      that of patients with schizophrenia, NRG1 is an appropriate candidate gene for
      METH-induced psychosis. We conducted a case-control association study between
      NRG1 and METH-induced psychosis in a Japanese population (184 subjects with METH
      induced psychosis and 534 controls). Written informed consent was obtained from
      each subject. We selected four SNPs (SNP8NRG221533, SNP8NRG241930, SNP8NRG243177,
      and rs3924999) in NRG1 from previous reports. No significant association was
      found between NRG1 and METH-induced psychosis in the allele/genotype-wise or
      haplotype-wise analyses. In conclusion, NRG1 might not contribute to the risk of
      METH-induced psychosis in the Japanese population.

PMID- 19394387
TI  - Trait anxiety and ethanol: anxiolysis in high-anxiety mice and no relation to
      intake behavior in an addiction model.
AB  - Anxiety has been proposed to play a role in the development of alcohol addiction,
      but the exact mechanisms by which this occurs remain unclear. The present study
      aimed to verify the relationship between basal anxiety levels, the anxiolytic
      like effect of ethanol, and ethanol intake in mice exposed to an addiction model.
      In one experiment Swiss mice were characterized as high-anxiety (HA), medium
      anxiety (MA), or non-anxiety (NA) in the elevated plus maze and then received
      saline or ethanol 2 g/kg acutely and chronically and were again exposed to the
      same test. NA mice decreased while MA mice maintained anxiety indices over the
      test days, regardless of treatment. HA ethanol-treated mice showed an anxiolytic
      like effect, both acutely and chronically, while the saline-treated ones
      maintained their basal anxiety levels. In another experiment HA and MA mice were
      exposed to an addiction model based on a 3-bottle free-choice paradigm (ethanol
      5% and 10%, and water) consisting of four phases: acquisition (10 weeks),
      withdrawal (W, 2 weeks), reexposure (2 weeks), and quinine-adulteration (2
      weeks). HA and MA control mice had access only to water. Mice were characterized
      as addicted, heavy-drinker and light-drinker [Fachin-Scheit DJ, Ribeiro AF,
      Pigatto G, Goeldner FO, Boerngen-Lacerda R. Development of a mouse model of
      ethanol addiction: naltrexone efficacy in reducing consumption but not craving. J
      Neural Transm 2006;113:1305-21.]. No difference was observed between HA and MA
      mice in their preference for and intake of ethanol. No correlation was observed
      between ethanol intake, during any phase, and anxiety indices measured in the
      basal tests and during the W phase. The differences in anxiety indices between HA
      and MA groups persisted in the test performed during ethanol withdrawal,
      suggesting a "trait" anxiety profile. The data suggest that despite the fact that
      high anxiety trait levels are important for the anxiolytic-like effects of
      ethanol, they are not a determining factor for high ethanol intake, at least not
      under these experimental conditions.

PMID- 19394388
TI  - Deficient inhibition of return for emotional faces in depression.
AB  - Depression is a commonly-occurred mental disorder. Researchers have highlighted
      the attentional bias of depressive disorders, although results have been mixed.
      The cue-target task has often been used to explore attentional bias; a particular
      phenomenon revealed by such studies is the inhibition of return (IOR). However,
      cue-target task has seldom been used so far in the study of depressed patients.
      The aim of the present study was to investigate the IOR phenomenon in depressed
      individuals in cue-target task using emotional faces as cues. Control
      participants who had never suffered depression (NC), participants who had
      experienced at least two depressive episodes in their lives but were currently
      remitted (RMD), and participants diagnosed with a current major depressive
      disorder (MDD), were recruited using BDI, BAI, HDRS and DSM-IV as tools.
      Seventeen participants in each group completed a cue-target task in a behavioral
      experiment that comprised three kinds of experimental condition, two cue types
      and four face types. Each participant also completed a simpler cue-target task in
      an event-related potential (ERP) experiment. In cue-target task, a target
      appeared after a cue and the participant responded to its location. In the
      behavioral experiment, it was found that when the stimulus onset asynchrony (SOA)
      was 14 ms, the NC and RMD participants had IOR effects for all faces and MDD
      participants for angry and sad faces. When the SOA was 250 ms, all three groups
      all had cue validity for sad faces but the effect was much more marked for the
      MDD group. When the SOA was 750 ms, the NC participants had an IOR effect for sad
      faces, the RMD participants had cue validity for angry, happy and sad faces, and
      the MDD participants had cue validity for sad faces and an IOR effect for angry
      faces. In the ERP experiment, the NC participants showed bigger P3 amplitude for
      happy cue compared with the other groups, smaller P1 amplitude for happy faces in
      the invalid cue condition than for other faces, smaller P1 amplitude for sad
      faces in the valid cue condition than for happy faces, bigger P3 amplitude for
      happy faces in the valid cue condition compared with MDD participants, and bigger
      P3 amplitude for sad faces in the invalid cue condition compared with other
      groups. The RMD participants had larger P3 amplitude for sad cue than for other
      faces, larger P3 amplitude for happy faces in the valid cue condition compared
      with MDD participants, and smaller P3 amplitude for sad faces in the invalid cue
      condition compared with NC participants. The MDD participants had larger P1
      amplitude for sad cue compared with other groups, larger P3 amplitude for sad cue
      than for other face cues, smaller P3 amplitude for sad faces in the invalid cue
      condition compared with NC participants, and smaller P3 amplitude for happy faces
      in the valid cue condition compared with other groups. It can be concluded that
      the MDD participants had cue validity and deficient IOR for negative stimuli. The
      deficient inhibition of negative stimuli renders them unable to eliminate the
      interference of negative stimuli and causes the maintenance and development of
      depression. The RMD participants had cue validity and deficient IOR for both
      positive and negative stimuli, which enables them to perceive positive and
      negative stimuli sufficiently and to maintain emotional balance.

PMID- 19394389
TI  - Is there really a link between hyperbilirubinemia and schizophrenia?

PMID- 19394390
TI  - Evaluation of Tualang honey as a supplement to fetal bovine serum in cell
      culture.
AB  - The aim of this study was to evaluate Tualang honey as a supplement to fetal
      bovine serum in cell cultures using MTT assay, chromosome aberration test and
      gene expression analyses. The MTT assay showed the highest percentage of cell
      proliferation (105.3% increment than control) of human osteoblast cell line (CRL
      1543) in 0.0195% honey in Dulbecco's modified eagle medium supplemented with 10%
      fetal bovine serum and 1% penicillin/streptomycin. There was enhanced cell
      proliferation corresponding to the decrease in concentrations of honey as
      indicated by the mitotic index values when the osteoblast cell line was incubated
      at 37 degrees C for 48 hours. There were no chromosome aberrations both in the
      honey treated as well as distilled water treated (negative control) cell lines.
      In the case of gene expression analyses, fibroblast cell lines (CCL 171) were
      treated with honey (0.0195%) for 24 and 48 hours separately. Though there was
      over expression for the bcl-xl gene at both 24 and 48 hours, under expression for
      bcl-xs gene at 24 hours and over expression at 48 hours and under expression for
      both c-myc and p53 genes at both 24 and 48 hours, none of them were statistically
      significant in altering the expression of mRNA.

PMID- 19394391
TI  - Mercury(II) and methyl mercury determinations in water and fish samples by using
      solid phase extraction and cold vapour atomic absorption spectrometry
      combination.
AB  - A method has been developed for mercury(II) and methyl mercury speciation on
      Staphylococcus aureus loaded Dowex Optipore V-493 micro-column in the presented
      work, by using cold vapour atomic absorption spectrometry. Selective and
      sequential elution with 0.1 molL(-1) HCl for methyl mercury and 2 molL(-1) HCl
      for mercury(II) were performed at the pH range of 2-6. Optimal analytical
      conditions including pH, amounts of biosorbent, sample volumes were investigated.
      The detection limits of the analytes were 2.5 ngL(-1) for Hg(II) and 1.7 ngL(-1)
      for methyl mercury. The capacity of biosorbent for mercury(II) and methyl mercury
      was 6.5 and 5.4 mgg(-1), respectively. The validation of the presented procedure
      is performed by the analysis of standard reference material. The speciation
      procedure established was successfully applied to the speciation of mercury(II)
      and methyl mercury in natural water and microwave digested fish samples.

PMID- 19394392
TI  - Indoor air contamination during a waterpipe (narghile) smoking session.
AB  - The smoke of waterpipe contains numerous substances of health concern, but people
      mistakenly believe that this smoking method is less harmful and addictive than
      cigarettes. An experiment was performed in a 57 m3 room on two dates with no
      smoking on the first date and waterpipe smoking for 4h on the second date. We
      measured volatile organic compounds (VOC), polycyclic aromatic hydrocarbons
      (PAH), metals, carbon monoxide (CO), nitrogen oxides (e.g. NO), as well as
      particle mass (PM), particle number concentration (PNC) and particle surface area
      in indoor air. High concentrations were observed for the target analytes during
      the 4-h smoking event. The median (90th percentile) values of PM(2.5), PNC, CO
      and NO were 393 (737 microg/m(3)), 289,000 (550,000 particles/cm(3)), 51 (65 ppm)
      and 0.11 (0.13 ppm), respectively. The particle size distribution has a maximum
      of particles relating to a diameter of 17 nm. The seven carcinogenic PAH were
      found to be a factor 2.6 higher during the smoking session compared to the
      control day. In conclusion, the observed indoor air contamination of different
      harmful substances during a WP session is high, and exposure may pose a health
      risk for smokers but in particular for non-smokers who are exposed to ETS.

PMID- 19394393
TI  - Safety assessment of kola nut extract as a food ingredient.
AB  - Kola nut extract is used in the food industry as a flavoring ingredient. Kola nut
      extract is derived from the seeds of primarily two tropical Cola species (Cola
      nitida (Vent.) Schott et Endl. or Cola acuminata (Beauv.) Schott et Endl.) of the
      Family, Sterculiaceae. Present day consumption of kola nut extract is 0.69
      mg/kg/day. Caffeine and theobromine are two important constituents of kola nuts.
      Although limited biological data are available for kola nut extract specifically,
      the published data of the major constituents of kola nuts suggest the
      pharmacological/toxicological properties of kola nut extract, parallel to those
      of a roughly equivalent dose of caffeine. Frank developmental/reproductive
      effects have not been reported and changes in offspring cannot be extrapolated to
      humans. A NOEL/NOAEL cannot be defined for repeated oral exposure to kola nut
      extract from available data. Notwithstanding the foregoing, U.S. consumers have a
      history of safe consumption of cola-type beverages containing kola nut extract
      that dates at least to the late 19th Century, with a significant global history
      of exposure to the intact kola nuts that date centuries longer.

PMID- 19394394
TI  - The effect of arsenic exposure and the efficacy of DMSA on the proteins and
      lipids of the gill tissues of Labeo rohita.
AB  - Arsenic is a naturally occurring, highly toxic environmental pollutant. Fourier
      transform infrared (FT-IR) spectroscopy is a non-disturbing technique which
      provides quantitative information about the molecular composition of biological
      samples. The aim of this work is to study the compositional and structural
      changes at the molecular level occurring in gill tissues of Labeo rohita
      fingerlings due to arsenic exposure for various exposure periods by using FT-IR
      spectroscopic technique. The results of the present study suggest that arsenic
      exposure causes significant changes on the major biochemical constituents such as
      proteins, lipids and nucleic acids in the gill tissues of L. rohita. The changes
      are more pronounced as the period of exposure is increased. The significant
      decrease in the intensity and area of the amide I peak and CH(3) asymmetric
      stretching band suggests an alteration in the protein profile and lipid levels
      respectively, due to arsenic exposure. The amide A peak shifts suggests a change
      in the level of protein amide hydrogen bonding due to arsenic exposure. Further,
      the treatment with meso-2,3-dimercaptosuccinic acid (DMSA) improves the levels of
      biochemical constituents significantly, which suggest that DMSA treatment reduces
      the toxic effects and helps the recovery of gill tissues and its return to the
      level of the control.

PMID- 19394395
TI  - Methiocarb-induced oxidative damage following subacute exposure and the
      protective effects of vitamin E and taurine in rats.
AB  - Methiocarb, is used worldwide in agriculture and health programs. Besides its
      advantages in the agriculture, it causes several toxic effects. In this study, we
      aimed to investigate subacute effects of methiocarb on lipid peroxidation,
      reduced glutathione (GSH), antioxidant enzymes such as superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase
      (GSH-Rd) and histopathological changes in rat tissues. Moreover, we examined the
      possible protective effects of vitamin E and taurine on methiocarb-induced
      oxidative damage in rat tissues. Rats were randomly divided into six groups as
      follows; I-control group; II-methiocarb group; III-vitamin E group; IV-vitamin
      E+methiocarb group; V-taurine group and VI-taurine+methiocarb group. Methiocarb
      significantly increased lipid peroxidation in liver and kidney when compared to
      control groups. Levels of GSH and activities of SOD, CAT and GSH-Px were found to
      be decreased, while GSH-Rd remained unchanged in rat liver and kidney treated
      with methiocarb. Pretreatment of vitamin E and taurine resulted in a significant
      decrease on lipid peroxidation, alleviating effects on GSH and antioxidant
      enzymes. The degenerative histological changes were less in liver than kidney of
      rats treated with methiocarb. Pretreatment of vitamin E and taurine showed a
      protective effect on the histological changes in kidney comparing to the liver of
      rats treated with methiocarb.

PMID- 19394396
TI  - Molecular modifications of cholesterol metabolism in the liver and the brain
      after chronic contamination with cesium 137.
AB  - Twenty years after Chernobyl accident, the daily ingestion of foodstuff grown on
      contaminated grounds remains the main source for internal exposure to ionizing
      radiations, and primarily to cesium 137 ((137)Cs). Though the effects of a long
      term internal contamination with radionuclides are poorly documented, several non
      cancerous pathologies have been described in this population. However, lipid
      metabolism was never investigated after chronic internal contamination although
      disturbances were observed in externally-exposed people. In this regard, we
      assessed the effects of a chronic ingestion of (137)Cs on hepatic and cerebral
      cholesterol metabolism. To mimic a chronically-exposed population, rats were
      given (137)Cs-supplemented water at a post-accidental dose (150 Bq/rat/day)
      during 9 months. The plasma profile, and brain and liver cholesterol
      concentrations were unchanged. A decrease of ACAT 2, Apo E, and LXR<alpha>mRNA
      levels was recorded in the liver. In the brain, a decrease of CYP27A1 and ACAT 1
      gene expression was observed. These results clearly show that cholesterol
      metabolism is not disrupted by a chronic ingestion of (137)Cs, although several
      molecular alterations are observed. This work would be interestingly completed by
      studying the influence of (137)Cs in models likely more sensitive to
      contaminants, such as the fetus or individuals susceptible to a lipidic disease.

PMID- 19394397
TI  - Caffeic acid phenethyl ester protects against tamoxifen-induced hepatotoxicity in
      rats.
AB  - Tamoxifen (TAM) is widely used in the treatment and prevention of breast cancer.
      Adverse effects of TAM include hepatotoxicity. Caffeic acid phenethyl ester
      (CAPE), an active component of propolis, has been used in folk medicine for
      diverse ailments. In the current study, the protective effects of CAPE against
      TAM-induced hepatotoxicity in female rats were evaluated. TAM (45 mg/kg/day,
      i.p., for 10 consecutive days) resulted in an elevation of serum alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase
      (ALP), depletion of liver reduced glutathione (GSH) and accumulation of oxidized
      glutathione (GSSG) and lipid peroxidation (LPO). Also, TAM treatment resulted in
      inhibition of hepatic activity of glutathione reductase (GR), glutathione
      peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT). Further, it
      raised liver tumor necrosis factor-alpha (TNF-alpha) level and induced
      histopathological changes. Pretreatment with CAPE (2.84 mg/kg/day; i.p., for 20
      consecutive days, starting 10 days before TAM injection) significantly prevented
      the elevation in serum activity of the assessed enzymes. CAPE significantly
      inhibited TAM-induced hepatic GSH depletion and GSSG and LPO accumulation.
      Consistently, CAPE normalized the activity of GR, GPx, SOD and CAT, inhibited the
      rise in TNF-alpha and ameliorated the histopathological changes. In conclusion,
      CAPE protects against TAM-induced hepatotoxicity.

PMID- 19394398
TI  - Hydrangea dulcis folium preserves beta-cell mass in diabetic db/db mice.
AB  - The anti-diabetic efficacy of Hydrangea dulcis folium (HDF) was studied in db/db
      mice and their littermates (db/-). Supplementation of HDF (1% and 3%) decreased
      glucose level significantly by 2- and 4-fold and increased significantly insulin
      level by 3- and 4.5-fold compared to db/db mice (P<0.05). Administration of HDF
      (1% and 3%) ameliorates hyperglycemia and improves glucose homeostasis in db/db
      mice in a dose-dependent manner by preventing loss of beta-cell mass resulting in
      increase of insulin secretion. In addition, 3% HDF treatment significantly
      reduced the food intake, weight gain, and blood lipids in db/db mice.

PMID- 19394399
TI  - Houttuynia cordata water extract suppresses anaphylactic reaction and IgE
      mediated allergic response by inhibiting multiple steps of FcepsilonRI signaling
      in mast cells.
AB  - Houttuynia cordata has been used as a traditional medicine in Korea and is known
      to have antioxidant, anti-cancer and anti-allergic activities. The precise effect
      of H. cordata, however, remains unknown. In this study, we investigated the
      effects of H. cordata water extract (HCWE) on passive cutaneous anaphylaxis (PCA)
      in mice and on IgE-mediated allergic response in rat mast RBL-2H3 cells. Oral
      administration of HCWE inhibited IgE-mediated systemic PCA in mice. HCWE also
      reduced antigen (DNP-BSA)-induced release of beta-hexosaminidase, histamine, and
      reactive oxygen species in IgE-sensitized RBL-2H3 cells. In addition, HCWE
      inhibited antigen-induced IL-4 and TNF-alpha production and expression in IgE
      sensitized RBL-2H3 cells. HCWE inhibited antigen-induced activation of NF-kappaB
      and degradation of IkappaB-alpha. To investigate the inhibitory mechanism of HCWE
      on degranulation and cytokine production, we examined the activation of
      intracellular FcepsilonRI signaling molecules. HCWE suppressed antigen-induced
      phosphorylation of Syk, Lyn, LAT, Gab2, and PLC gamma2. Further downstream,
      antigen-induced phosphorylation of Akt and MAP kinases (ERK1/2 and JNK1/2 but not
      p38 MAP kinase) were inhibited by HCWE. Taken together, the in vivo/in vitro anti
      allergic effect of HCWE suggests possible therapeutic applications of this agent
      in inflammatory allergic diseases through inhibition of cytokines and multiple
      events of FcepsilonRI-dependent signaling cascades in mast cells.

PMID- 19394400
TI  - Cholinesterase inhibitory effects of the extracts and compounds of Maclura
      pomifera (Rafin.) Schneider.
AB  - We have investigated anticholinesterase potential of the methanol extracts from
      the leaf, wood, flower, twig, and stem bark of the female and male individuals
      and rhizodermis and fruit from the female tree of Maclura pomifera (Rafin.)
      Schneider (Moraceae) along with its major isoflavonoids; osajin and pomiferin as
      well as their semi-synthetic derivatives; iso-osajin and iso-pomiferin.
      Anticholinesterase activity was determined by Ellman method using ELISA
      microplate reader. Osajin and pomiferin had a noticeable inhibition of AChE with
      IC(50) values of 2.239 and 0.096 mM, respectively, while their iso-derivatives
      were found to display less inhibition towards AChE. The extracts and compounds
      did not inhibit BChE. The extracts were analyzed for osajin and pomiferin
      contents by LC-DAD-MS and only the fruits and female flowers contained osajin
      (fruit: 8.87%, female flowers: 0.19%, w/w) and pomiferin (fruit: 13.6%, female
      flowers: 0.36%, w/w).

PMID- 19394401
TI  - Neutral sphingomyelinase-induced ceramide accumulation by oxidative stress during
      carbon tetrachloride intoxication.
AB  - Ceramide is a biologically active lipid causing apoptosis in a variety of cells.
      In this study, we examined the effect of CCl4 on the ceramide metabolism and
      indicators of oxidative stress. After 12 h of oral administration of CCl4 (4
      ml/kg body weight as a 1:1 mixture of CCl4 and mineral oil) to rats, aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) were increased.
      Antioxidants such as vitamins C and E were decreased in the liver and kidney. In
      addition, the ratio of GSH/GSSG in the liver, plasma, kidney, and brain decreased
      at 2h. The total ceramide in the liver significantly increased as early as 2h
      after CCl4 administration. After 24 and 36 h, the total ceramide in plasma and
      the kidney was also augmented. In the brain, the total ceramide dramatically
      increased at 36 h. These results suggested that the increased ceramide in plasma
      was transferred to the kidney and the brain. The activity of neutral
      sphingomyelinase (SMase), which was reported to be enhanced by the decrease of
      GSH, was significantly increased after CCl4 treatment in the liver, kidney, and
      brain. However, acid SMase activities were not increased in the liver and kidney.
      Thus, the activation of neutral SMase via oxidative stress induced the increase
      of ceramide during CCl4 intoxication in not only the liver but also other
      tissues. These results suggested that the excess accumulation of ceramide causes
      damage in other organs including the kidney and brain during fulminant hepatic
      failure.

PMID- 19394402
TI  - Multiplexed quantitative high content screening reveals that cigarette smoke
      condensate induces changes in cell structure and function through alterations in
      cell signaling pathways in human bronchial cells.
AB  - Human bronchial cells are one of the first cell types exposed to environmental
      toxins. Toxins often activate nuclear factor-kappaB (NF-kappaB) and protein
      kinase C (PKC). We evaluated the hypothesis that cigarette smoke condensate
      (CSC), the particulate fraction of cigarette smoke, activates PKC-alpha and NF
      kappaB, and concomitantly disrupts the F-actin cytoskeleton, induces apoptosis
      and alters cell function in BEAS-2B human bronchial epithelial cells. Compared to
      controls, exposure of BEAS-2B cells to doses of 30mug/ml CSC significantly
      activated PKC-alpha, while CSC doses above 20mug/ml CSC significantly activated
      NF-kappaB. As NF-kappaB was activated, cell number decreased. CSC treatment of
      BEAS-2B cells induced a decrease in cell size and an increase in cell surface
      extensions including filopodia and lamellipodia. CSC treatment of BEAS-2B cells
      induced F-actin rearrangement such that stress fibers were no longer prominent at
      the cell periphery and throughout the cells, but relocalized to perinuclear
      regions. Concurrently, CSC induced an increase in the focal adhesion protein
      vinculin at the cell periphery. CSC doses above 30mug/ml induced a significant
      increase in apoptosis in BEAS-2B cells evidenced by an increase in activated
      caspase 3, an increase in mitochondrial mass and a decrease in mitochondrial
      membrane potential. As caspase 3 increased, cell number decreased. CSC doses
      above 30mug/ml also induced significant concurrent changes in cell function
      including decreased cell spreading and motility. CSC initiates a signaling
      cascade in human bronchial epithelial cells involving PKC-alpha, NF-kappaB and
      caspase 3, and consequently decreases cell spreading and motility. These CSC
      induced alterations in cell structure likely prevent cells from performing their
      normal function thereby contributing to smoke-induced diseases.

PMID- 19394404
TI  - The multi-faceted basis of vitamin B12 (cobalamin) neurotrophism in adult central
      nervous system: Lessons learned from its deficiency.
AB  - Glial cells, myelin and the interstitium are the structures of the mammalian
      central nervous system (CNS) mainly affected by vitamin B(12) (cobalamin, Cbl)
      deficiency. Most of the response to the damage caused by Cbl deficiency seems to
      come from astrocytes and microglia, and is manifested as an increase in the
      number of cells positive for glial fibrillary acidic protein, the presence of
      ultrastructural signs of activation, and changes in cytokine and growth factor
      production and secretion. Myelin damage particularly affects the lamellae, which
      are disorganized by edema, as is the interstitium. Surprisingly, rat Schwann
      cells (myelin-forming cells of the peripheral nervous system) are fully activated
      but the few oligodendrocytes (myelin-forming cells of the CNS) are scarcely
      activated. The presence of intramyelin and interstitial edema raises questions
      about the integrity of the blood-brain barrier and blood-cerebrospinal fluid
      (CSF) barrier. The results obtained in the CNS of Cbl-deficient rats indicate
      that cytokine and growth factor imbalance is a key point in the pathogenesis of
      Cbl-deficient neuropathy. In the rat, Cbl deficiency increases the spinal cord
      (SC) synthesis and CSF levels of myelinotoxic cytokines (tumor necrosis factor
      (TNF)-alpha and soluble (s) CD40:sCD40 ligand dyad) and a myelinotoxic growth
      factor (nerve growth factor), but decreases SC synthesis and CSF levels of a
      myelinotrophic cytokine (interleukin-6) and a myelinotrophic growth factor
      (epidermal growth factor, EGF). The in vivo administration of IL-6 or EGF, or
      agents antagonizing the excess myelinotoxic agent, is as effective as Cbl in
      repairing or preventing Cbl-deficiency-induced CNS lesions. An imbalance in TNF
      alpha and EGF levels has also been found in the CSF and serum of patients with
      severe Cbl deficiency.

PMID- 19394405
TI  - Intracellular targeting and clearance of oligomeric alpha-synuclein alleviates
      toxicity in mammalian cells.
AB  - Intracellular clearance of toxic protein aggregates represents a promising
      therapeutic approach to treat protein-misfolding diseases such as Parkinson's and
      Huntington's diseases. Intracelluarly expressed antibody fragments or intrabodies
      can be used to bind specific intracellular targets. Addition of a non-traditional
      secretion signal sequence enables the intrabody to first bind its target inside
      the cell and then shuttle the bound target through the cell membrane, secreting
      it from the cell. We intracellularly expressed two different single chain
      antibody (scFv) fragments targeting either monomeric or oligomeric alpha
      synuclein (a-syn), in a mammalian cell model that overexpresses a-syn. Two
      versions of each intrabody were studied, one with and one without the non
      traditional secretion signal. The scFv targeting monomeric a-syn provided little
      or no reduction in toxicity induced by overexpression of a-syn, however binding
      and secretion of oligomeric a-syn totally reduced toxicity. Non-traditional
      intrabody secretion therefore represents an effective method to target and clear
      a variety of harmful intracellular species.

PMID- 19394403
TI  - Of mice, rats and men: Revisiting the quinolinic acid hypothesis of Huntington's
      disease.
AB  - The neurodegenerative disease Huntington's disease (HD) is caused by an expanded
      polyglutamine (polyQ) tract in the protein huntingtin (htt). Although the gene
      encoding htt was identified and cloned more than 15 years ago, and in spite of
      impressive efforts to unravel the mechanism(s) by which mutant htt induces nerve
      cell death, these studies have so far not led to a good understanding of
      pathophysiology or an effective therapy. Set against a historical background, we
      review data supporting the idea that metabolites of the kynurenine pathway (KP)
      of tryptophan degradation provide a critical link between mutant htt and the
      pathophysiology of HD. New studies in HD brain and genetic model organisms
      suggest that the disease may in fact be causally related to early abnormalities
      in KP metabolism, favoring the formation of two neurotoxic metabolites, 3
      hydroxykynurenine and quinolinic acid, over the related neuroprotective agent
      kynurenic acid. These findings not only link the excitotoxic hypothesis of HD
      pathology to an impairment of the KP but also define new drug targets and
      therefore have direct therapeutic implications. Thus, pharmacological
      normalization of the imbalance in brain KP metabolism may provide clinical
      benefits, which could be especially effective in early stages of the disease.

PMID- 19394406
TI  - Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by l
      carnosine in SH-SY5Y cells.
AB  - Conditions that cause endoplasmic reticulum malfunction (ER stress) play a key
      role in the development of various human diseases including neurodegenerative
      diseases. Carnosine is an endogenous peptide, present in excitable tissues such
      as brain and skeletal muscle. Although there are reports suggesting that
      carnosine has a biological role independent of its antioxidant activity, there
      have been no reports of the effects of carnosine on the ER stress response. We
      investigated the effects of carnosine on 6-hydroxydopamine (6-OHDA)-induced cell
      death and ER stress in SH-SY5Y cells. After assessing control cell viability in
      serum-free conditions for 24h (100% viability), we found that 50 microM 6-OHDA
      reduced cell viability to 76.4% of control values, whereas addition of 10mM
      carnosine significantly reduced cell death to 96.1% viability in a dose-dependent
      manner. Consistent with its cytoprotective action, carnosine markedly inhibited
      subsequent ER stress responses, including phosphorylation of eukaryotic
      initiation factor 2alpha (eIF2alpha) and c-jun, expression of glucose regulatory
      protein 78 and C/EBP homologous protein, and mRNA splicing of X-box protein 1.
      The measurement of reactive oxygen species (ROS) generation by 6-OHDA showed that
      addition of 10mM carnosine slightly but obviously inhibits the 6-OHDA-induced ROS
      production. In conclusion, our results show that carnosine almost completely
      inhibits 6-OHDA-induced ER stress responses and cytotoxicity, and that slight
      antioxidant activity of carnosine against 6-OHDA is observed. Further in vivo
      studies are needed to investigate clinical uses for carnosine.

PMID- 19394407
TI  - Comparison of adult neurospheres derived from different origins for treatment of
      rat spinal cord injury.
AB  - This study is designed to evaluate the therapeutic effects of three types of
      neurospheres (NSs) derived from brain, bone marrow and adipose tissue in a rat
      model of spinal contusive injury. As shown by BBB locomotor rating scale and grid
      test, the optimal therapeutic responses generated by subventricular zone-derived
      NSs (SVZ-NSs), and followed by adipose-derived (AD-NSs) and bone marrow-derived
      NSs (BM-NSs) after being grafted into the injured spinal cord. In three cell
      treated groups, very few (<1%) grafted cells survived and these survived cells
      mainly differentiated into oligodendrocytes at week 12 after injury.
      Additionally, all the cell-treated groups, especially in the SVZ-treated group
      showed an increase in host oligodendrocytes than control group. Moreover, the
      level of selective neurotrophins (NTs) in the SVZ-NSs group were significantly
      higher than those in the BM-NSs and AD-NSs groups, and the level of NTs in the
      saline group was also significantly higher than sham group. Therefore, not cell
      replacement or infusion but neuroprotective action associated with endogenous
      oligodendrocytes and NTs that active by the grafted NSs may contribute to the
      functional recovery.

PMID- 19394408
TI  - Association between promoter polymorphisms of the nicastrin gene and sporadic
      Alzheimer's disease in North Chinese Han population.
AB  - Increasing evidences have shown that nicastrin (NCSTN) plays a crucial role in
      gamma-cleavage of the amyloid precursor protein (APP). Inhibition of NCSTN
      demonstrated an altered gamma-cleavage activity, suggesting its potential
      implication in developing Alzheimer's disease (AD). We detected the NCSTN gene
      promoter region in 359 sporadic AD (SAD) patients and 331 controls and found
      three promoter single nucleotide polymorphisms (SNPs): -1216C/A (rs2147471), 
      796T/G (rs10752637) and -436C/T (rs1324738). For -1216C/A, there were significant
      differences in the allele and genotype frequency between AD and control subjects
      (allele P=0.031, genotype P=0.017). The allele and genotype frequencies remained
      significant before and after APOEvarepsilon4 stratification. The -1216CC carriers
      increased 2-fold risk for the development of SAD compared to the carriers with 
      1216CA and AA genotypes (OR=2.049, 95%CI=1.410-2.976, P=0.000). For -796T/G,
      there were significant differences in the genotype frequency between SAD and
      control subjects (P=0.009). This trend is still obvious in the subjects without
      APOEvarepsilon4 allele. The -796GG carriers might decrease the risk compared to
      the carriers with -796TG and TT genotypes (OR=0.602, 95%CI=0.393-0.932, P=0.022).
      No significant difference was detected either in genotype or in allele
      frequencies between SAD and control for -436C/T, even after APOEvarepsilon4
      stratification. The haplotype -1216A/-796G may be a protective factor for SAD
      (OR=0.795, 95%CI=0.636-0.995, P=0.045). Our investigation suggests that -1216C/A
      and -796T/G are probably related to the development of SAD.

PMID- 19394409
TI  - Verdoheme formation in Proteus mirabilis catalase.
AB  - BACKGROUND: Heme oxidative degradation has been extensively investigated in
      peroxidases but not in catalases. The verdoheme formation, a product of heme
      oxidation which inactivates the enzyme, was studied in Proteus mirabilis
      catalase. METHODS: The verdoheme was generated by adding peracetic acid and
      analyzed by mass spectrometry and spectrophotometry. RESULTS: Kinetics follow-up
      of different catalase reactional intermediates shows that i) the formation of
      compound I always precedes that of verdoheme, ii) compound III is never observed,
      iii) the rate of compound II decomposition is not compatible with that of
      verdoheme formation, and iv) dithiothreitol prevents the verdoheme formation but
      not that of compound II, whereas NADPH prevents both of them. The formation of
      verdoheme is strongly inhibited by EDTA but not increased by Fe3+ or Cu2+ salts.
      The generation of verdoheme is facilitated by the presence of protein radicals as
      observed in the F194Y mutated catalase. The inability of the inactive variant
      (H54F) to form verdoheme, indicates that the heme oxidation is fully associated
      to the enzyme catalysis. CONCLUSION: These data, taken together, strongly suggest
      that the verdoheme formation pathway originates from compound I rather than from
      compound II. GENERAL SIGNIFICANCE: The autocatalytic verdoheme formation is
      likely to occur in vivo.

PMID- 19394410
TI  - Spontaneous movement tempo is influenced by observation of rhythmical actions.
AB  - Observation of people performing movements facilitates motor planning, execution
      and memory formation. Tempo, a crucial aspect involved in the execution of
      rhythmic movements, is normally perceived and learned through auditory channels.
      In this work, we ascertained whether: first, the frequency of self-paced finger
      movements (SPMs), which in normal subjects is around 2 Hz, is modified by prior
      observation of movements performed at either 1 or 3 Hz; second, such changes are
      lasting; third, there is an effect of time interval between observation and
      performance. We finally determined the effect of providing explicit information
      about the upcoming motor task. Seventy-two normal subjects (12 groups) performed
      a simple finger sequence at different intervals after observation of videos of
      either landscapes or finger opposition movements. Both with and without
      information about the upcoming task, observation influenced the tempo of SPMs and
      led to memory formation. With knowledge of the upcoming task, such changes
      occurred at all observation-execution intervals, while without instructions,
      changes took place only when SPMs were performed immediately after observation.
      Compared to explicit instructions, the absence of instructions produced tempo's
      changes that more closely resembled the observed rhythms. We conclude that
      learning requires a prompt comparison between visual and sensorimotor
      representations of movements; moreover, learning with explicit instructions is
      more efficient, as activity in both the dorsal and ventral streams might be
      potentiated by the chatecholaminergic attentional systems that promote long-term
      potentiation. These results provide the bases for novel neurorehabilitation
      strategies in terms of temporal re-organization of movement.

PMID- 19394411
TI  - An expeditious HPLC method to distinguish Aconitum kusnezoffii from related
      species.
AB  - An optimized HPLC-DAD method aided by similarity and hierarchical clustering
      analysis (HCA) was applied for identification of four species of the roots of
      Aconitum. The unique properties of this HPLC fingerprints and HCA were validated
      by analyzing Aconitum kusnezoffii Rchb. (AKR) samples and related herbs including
      A. karacolicum Rapcs. (AKP) samples, A. austroyunnanense W.T.Wang (AAW) samples
      and A. contortum Finet & Gagnepain (ACF). The results revealed that the
      chromatographic fingerprint combining similarity measurement and hierarchical
      cluster analysis could efficiently identify and distinguish AKR samples from its
      related species.

PMID- 19394413
TI  - Formulation and in vitro assessment of minoxidil niosomes for enhanced skin
      delivery.
AB  - Niosomes have been reported as a possible approach to improve the low skin
      penetration and bioavailability characteristics shown by conventional topical
      vehicle for minoxidil. Niosomes formed from polyoxyethylene alkyl ethers (Brij)
      or sorbitan monoesters (Span) with cholesterol molar ratios of 0, 1 and 1.5 were
      prepared with varying drug amount 20-50mg using thin film-hydration method. The
      prepared systems were characterized for entrapment efficiency, particle size,
      zeta potential and stability. Skin permeation studies were performed using static
      vertical diffusion Franz cells and hairless mouse skin treated with either
      niosomes, control minoxidil solution (propylene glycol-water-ethanol at 20:30:50,
      v/v/v) or a leading topical minoxidil commercial formulation (Minoxyl). The
      results showed that the type of surfactant, cholesterol and incorporated amount
      of drug altered the entrapment efficiency of niosomes. Higher entrapment
      efficiency was obtained with the niosomes prepared from Span 60 and cholesterol
      at 1:1 molar ratio using 25mg drug. Niosomal formulations have shown a fairly
      high retention of minoxidil inside the vesicles (80%) at refrigerated temperature
      up to a period of 3 months. It was observed that both dialyzed and non-dialyzed
      niosomal formulations (1.03+/-0.18 to 19.41+/-4.04%) enhanced the percentage of
      dose accumulated in the skin compared to commercial and control formulations
      (0.11+/-0.03 to 0.48+/-0.17%) except dialyzed Span 60 niosomes. The greatest skin
      accumulation was always obtained with non-dialyzed vesicular formulations. Our
      results suggest that these niosomal formulations could constitute a promising
      approach for the topical delivery of minoxidil in hair loss treatment.

PMID- 19394412
TI  - The serpin gene family in Anopheles gambiae.
AB  - Serpins (serine protease inhibitors) regulate some innate immune responses of
      insects by inhibiting endogenous proteases. In this study, we characterized the
      serpin (SRPN) gene family in the mosquito Anopheles gambiae, the major malaria
      vector in Sub-Saharan Africa. We identified 18 A. gambiae SRPN genes, all on
      chromosomes 2 and 3, through searches of genomic DNA and EST databases. In
      addition to SRPN10, previously documented to exhibit alternative splicing, we
      found three splicing isoforms of SRPN4. We completed sequencing of cDNAs for the
      A. gambiae serpins to obtain complete coding sequence information and to verify
      or improve gene predictions. The predicted SRPN9 and 15 in the initial genome
      annotation were determined to be a single gene (SRPN9). Sixteen of the serpins
      contained putative secretion signal sequences. Multiple sequence alignments
      showing conserved residues important in structural conformation, including the
      consensus pattern within the hinge region, indicated that most of the A. gambiae
      serpins may be inhibitory. Phylogenetic analyses confirmed that SRPN1, 2, 3, 8, 9
      and 10 formed phylogenetic clusters with known inhibitory serpins from Drosophila
      melanogaster and Manduca sexta. Many of the A. gambiae serpins were expressed
      during all life stages. However, SRPN7, 8, 12, and 19 were expressed at very low
      levels in the adult stage. SRPN13 was expressed mostly in eggs and young larvae,
      whereas SRPN5 and 14 were expressed mostly in adults. Such differences in
      expression pattern suggest that the serpins are involved in multiple
      physiological processes. Determining the biological functions of the mosquito
      serpins will require future work to identify the proteases they inhibit in vivo.

PMID- 19394414
TI  - pH-sensitive properties of surface charge-switched multifunctional polymeric
      micelle.
AB  - A surface charge-switched polymeric micelle with a pH signal was developed as a
      drug-carrying nanovehicle for tumor targeting. The micelles (particle size:
      approximately 85 nm), constructed from poly(L-lactic acid)-b-poly(ethylene
      glycol)-b-poly(L-lysine-N(epsilon)-(2,3-dimethyl maleic acid)) (PLA-b-PEG-b-PLys
      DMA) and formed by self-assembly in an aqueous pH 7.4 solution, consisted of a
      hydrophobic core (PLA core) and two hydrophilic shells (PEG shell and PLys-DMA
      shell). An anionic charge can be built on the surface of the micelle at a
      physiological pH (approximately pH 7.4) due to 2,3-dimethyl maleic acid (DMA).
      However, DMA becomes chemically dissociated from the micelle under mild acidic
      conditions (pH 6.5-7.0) such as that found in solid tumors, which results in the
      formation of a cationic surface due to the poly(L-lysine) (PLys). This pH
      triggered switch in surface charge may enhance cellular uptake of micelles to
      solid tumors, via an adsorptive endocytotic pathway due to the electrostatic
      interaction between micelles and cells. In addition, blending of the poly(L
      histidine) (polyHis) into the hydrophobic core provides a mechanism for endosomal
      pH-triggered drug-release from the polymeric micelle. These combined properties
      of the polymeric micelle may aid in tumor-specific drug accumulation and allow it
      to be used as an effective treatment for tumors.

PMID- 19394415
TI  - Effect of gamma-ray irradiation on degradation of di(2-ethylhexyl)phthalate in
      polyvinyl chloride sheet.
AB  - The risk assessment of di(2-ethylhexyl)phthalate (DEHP) migration from polyvinyl
      chloride (PVC) medical devices is an important issue for patients. The aim of
      this study was to determine DEHP degradation and migration from PVC sheets. To
      this end, the method for the simultaneous determination of DEHP and its breakdown
      products (mono(2-ethylhexyl)phthalate (MEHP) and phthalic acid (PA)) was
      improved. Their migration levels from 0 to 50 kGy gamma-ray irradiated PVC sheets
      were determined. DEHP migration level decreased in proportion to the dose of
      gamma-ray irradiation, while MEHP and PA migration levels increased. The hardness
      and the elastic modulus of PVC sheets were examined, but no clear relationship
      between DEHP migration and these parameters was observed.

PMID- 19394416
TI  - Enhanced bioavailability of the poorly water-soluble drug fenofibrate by using
      liposomes containing a bile salt.
AB  - The main purpose of this study was to evaluate oral bioavailability of the poorly
      water-soluble drug fenofibrate when liposomes containing a bile salt were used as
      oral drug delivery systems. Liposomes composed of soybean phosphotidylcholine
      (SPC) and sodium deoxycholate (SDC) were prepared by a dry-film dispersing method
      coupled with sonication and homogenization. Several properties of the liposomes,
      including particle size, entrapment efficiency and membrane fluidity, were
      extensively characterized. In vitro release experiments indicated that no more
      than 20% of total fenofibrate was released from SPC/cholesterol (CL) and SPC/SDC
      liposomes at 2 h, in contrast with near complete release for micronized
      fenofibrate capsules. Strikingly, in vivo measurements of pharmacokinetics and
      bioavailability demonstrated higher rates of fenofibrate absorption from both
      SPC/SDC and SPC/CL liposomes than micronized fenofibrate. The bioavailability of
      SPC/SDC and SPC/CL liposomes was 5.13- and 3.28-fold higher, respectively, than
      that of the micronized fenofibrate. The disparity between oral bioavailability
      and in vitro release for liposomes strongly suggests alternative absorption
      mechanisms rather than enhanced release. Importantly, SPC/SDC liposomes exhibited
      a 1.57-fold increase in bioavailability relative to SPC/CL liposomes, indicating
      that liposomes containing bile salts may be used to enhance oral bioavailability
      of poorly water-soluble drugs.

PMID- 19394417
TI  - Comparison of identical single nucleotide polymorphisms genotyped by the GeneChip
      Targeted Genotyping 25K, Affymetrix 500K and Illumina 550K platforms.
AB  - Comparisons of targeted genotyping chips to ready-made chips are important
      because targeted chips are suitable for fine-scale association mapping with a
      reasonable cost. Genotypes produced by the Affymetrix Targeted Genotyping (TG)
      25K, Affymetrix 500K, and Illumina 550K arrays for regions on chromosomes 2 and 7
      of 90 individuals were assessed to investigate genotype accordance between the
      platforms. The common SNPs in TG the Affymetrix and Illumina arrays showed
      similar genotype accordance. The consistency rate of the Illumina array to
      consensus genotypes, i.e., identically called by more than two platforms, was the
      highest, and that of the Affymetrix array was the lowest. The TG array data
      showed high accordance and reasonable consistency between platforms.

PMID- 19394418
TI  - Detrimental consequences of brain injury on peripheral cells.
AB  - Acute brain injury and brain death exert detrimental effects on peripheral host
      cells. Brain-induced impairment of immune function makes patients more vulnerable
      to infections that are a major cause of morbidity and mortality after stroke,
      trauma, or subarachnoid hemorrhage (SAH). Systemic inflammation and organ
      dysfunction are other harmful consequences of CNS injury. Brain death, the most
      severe consequence of brain injury, causes inflammatory changes in peripheral
      organs that can contribute to the inferior outcome of organs transplanted from
      brain-dead donors. Understanding of the mechanisms underlying the detrimental
      effects of brain injury on peripheral organs remains incomplete. However, it
      appears that sympathetic nervous system (SNS)-activation contributes to elicit
      both inflammation and immunodepression. Indeed, norepinephrine (NE)-induced
      production of chemokines in liver and other organs likely participates in local
      and systemic inflammatory changes. Conversely, catecholamine-stimulated
      interleukin-10 (IL-10) production by blood monocytes exerts immunosuppressive
      effects. Activation of the hypothalamic-pituitary-adrenal axis (HPA) by increased
      inflammatory cytokines within the brain is a significant component in the CNS
      induced immune function inhibition. Non-neurologic consequences of brain injury
      show impressive similarities regardless of the brain insult and appear to depend
      on altered neuroimmune circuits. Modulation of these circuits could reduce extra
      brain damage and improve patient outcome in both vascular and traumatic brain
      injury.

PMID- 19394419
TI  - Moderate use of alcohol, tobacco and cannabis during pregnancy: new approaches
      and update on research findings.
AB  - Interest in fetal origins of adverse offspring outcomes has grown extensively in
      the last decade. This has resulted in many published studies focusing on exposure
      in utero to substances and human offspring outcomes. Exposure to maternal
      substance use in pregnancy is believed to be a preventable hazard, and is
      therefore a main issue for public health concern and policy. However, an
      important question in human studies remains whether prenatal substance use
      exposure has an aetiological role in pathways to adverse developmental and
      behavioural outcomes via teratological effects. Recent insights and developments
      in research methodology will aid the adequate and more refined testing of
      associations between prenatal substance use and offspring outcomes. In
      particular, novel approaches could assist in disentangling the exposure to
      substance effects from correlated risk factors. The purpose of this manuscript is
      therefore to provide an overview of methodological issues involved in studies
      that focus on the association between maternal substance use during pregnancy and
      offspring's outcomes, to describe novel approaches to test these associations,
      and present some examples of new and well-designed studies and discuss their
      findings.

PMID- 19394420
TI  - Decreased ABCB1 mRNA expression induced by atorvastatin results from enhanced
      mRNA degradation in HepG2 cells.
AB  - The mechanisms underlying atorvastatin supression of ABCB1 gene expression, at
      transcriptional and post-transcriptional levels of ABCB1 gene in HepG2 (human
      hepatocellular carcinoma) cells were investigated. Quantitative real-time PCR was
      used to measure mRNA levels, as well as to estimate the half-life of ABCB1 mRNA.
      Western blotting analysis was performed in order to measure protein levels of
      ABCB1. Electrophoretic mobility shift assay (EMSA) was used to evaluate
      interactions between protein(s) and ABCB1 promoter region. Exposure to
      atorvastatin for 24h resulted in a dose-dependent decrease of ABCB1 mRNA and
      protein levels, which was not abolished by addition of farnesyl or geranylgeranyl
      pyrophosphate. After removing fetal bovine serum from the media, however, ABCB1
      expression was decreased by 2-fold in either HepG2 cells treated and non-treated
      with atorvastatin. Addition of cholesterol to serum free media abolished this
      latter effect on ABCB1 mRNA levels. In EMSA using a 5'-end-labeled 241bp ABCB1
      promoter DNA fragment (-198 to +43) as probe, the binding of the proteins to the
      probe was reduced by NF-Y, but not changed by NFkappaB, AP-1, and SP1. However,
      the NF-Y binding activity was similar in control and atorvastatin-treated cells.
      mRNA stability studies revealed that ABCB1 mRNA degradation was increased in 1,
      10 and 20muM atorvastatin-treated versus control cells (half-lives of 2h versus
      7h). Therefore, evidence is provided that decreased mRNA stability by
      atorvastatin treatment may explain the decrease in ABCB1 transcript levels.

PMID- 19394421
TI  - Correlating thermodynamic and kinetic parameters with amorphous stability.
AB  - Poor physical stability is one of the single most important factors limiting the
      widespread use of the amorphous state in pharmaceutics. The purpose of this study
      is to move away from the case study approach by investigating thermodynamic and
      kinetic parameters as potential predictors of physical stability of amorphous
      drugs for a larger sample set (12 drugs). The relaxation time, fragility index
      and configurational thermodynamic properties (enthalpy, entropy and Gibbs free
      energy) were calculated and correlated to the actual stability behaviour,
      obtained for 12 drugs. Below the glass transition temperature the relaxation time
      and fragility showed no correlation with the observed physical stability. All
      drugs were calculated to be 'fragile'. However, variation in the fragility index
      existed, with values spanning from 8.9 to 21.3, manifesting themselves as
      differences in the temperature dependencies of the relaxation times. A reasonable
      correlation between the thermodynamic parameters and the stability above T(g) was
      found, with the configurational entropy exhibiting the strongest correlation
      (r(2)=0.685). However, it could also be shown that below T(g) no clear
      relationship between the various factors determined and physical stability
      exists, indicating that stability predictions on the basis of relaxation time
      alone may be inadequate.

PMID- 19394422
TI  - The hyaluronan-protein complexes at low ionic strength: how the hyaluronidase
      activity is controlled by the bovine serum albumin.
AB  - Hyaluronan (HA) hydrolysis catalysed by hyaluronidase (HAase) is strongly
      inhibited when performed at low HAase over HA concentration ratio and under low
      ionic strength conditions. The reason is the ability of long HA chains to form
      electrostatic and non-catalytic complexes with HAase. For a given HA
      concentration, low HAase concentrations lead to very low hydrolysis rates because
      all the HAase molecules are sequestered by HA, whilst high HAase concentrations
      lead to high hydrolysis rates because the excess of HAase molecules remains free
      and active. At pH 4, non-catalytic proteins like bovine serum albumin (BSA) are
      able to compete with HAase to form electrostatic complexes with HA, liberating
      HAase which recovers its catalytic activity. The general scheme for the BSA
      dependency is thus characterised by four domains delimited by three noticeable
      points corresponding to constant BSA over HA concentration ratios. The existence
      of HA-protein complexes explains the atypical kinetic behaviour of the HA / HAase
      system. We also show that HAase recovers the Michaelis-Menten type behaviour when
      the HA molecule complexed with BSA in a constant complexion state, i.e. with the
      same BSA over HA ratio, is considered for substrate. When the ternary HA / HAase
      / BSA system is concerned, the stoichiometries of the HA-HAase and HA-BSA
      complexes are close to 10 protein molecules per HA molecule for a native HA of 1
      MDa molar mass. Finally, we show that the behaviour of the system is similar at
      pH 5.25, although the efficiency of BSA is less.

PMID- 19394423
TI  - Improving frequency of thrombosis by altering blood flow in the carrageenan
      induced rat tail thrombosis model.
AB  - The carrageenan-induced tail thrombosis model in rats and mouse is useful for
      evaluating compounds having antithrombotic effects in drug discovery projects as
      an in vivo model. However, the frequency of thrombosis is low, and the signs of
      thrombosis are not constant under the standard conditions. In this study, we
      modified this model on the basis of hypercoagulability, endothelial injury, and
      alteration in the normal blood flow. The simple ligation to alter blood flow in
      rats significantly improved the frequency and signs of thrombosis after
      intravenous kappa-carrageenan injection. In particular, 1mg/kg kappa-carrageenan
      injection in combination with 10 min ligation at the tail increased the frequency
      of thrombosis to almost 100% in rats. These results suggest that this modified
      model has great advantages over the previously used conditions for evaluating the
      effects of antithrombotic and thrombolytic agents.

PMID- 19394424
TI  - Contractile response of norepinephrine is modulated by caspase-3 in adult rat
      ventricular myocytes isolated from septic rat heart.
AB  - Sepsis accounts for 50% of intensive care unit deaths due to cardiac dysfunction.
      The cellular mechanisms following norepinephrine (NE) during sepsis are
      undefined. Using a septic adult rat ventricular myocyte (ARVM) paradigm, we
      examined the molecular mechanism responsible for the blunted contractile response
      of NE. We tested the hypothesis that NE-induced increases in active caspase-3
      contribute to sepsis-induced ARVM contractile dysfunction. Single ARVMs were
      isolated from hearts harvested from sham and septic male rats. The contractile
      properties and expression of caspase-3 cascade proteins were determined in ARVMs
      treated with NE with and without QVD-OPH, prazosin and atenolol to characterize
      the effect of NE on their mechanical properties. Septic ARVMs exhibited a
      significant decrease in peak shortening (PS) compared to sham ARVMs. The effect
      of NE on the PS of the sham ARVMs was more pronounced compared to the septic
      ARVMs, suggesting a blunted contractile response of NE. NE in the presence of QVD
      OPH ameliorated the sepsis-induced decrease in PS at 18h but not at 1h, while the
      effect of NE on sepsis-induced contractile response remained unaffected at 18h by
      prazosin and atenolol. An up-regulated expression of caspase-3 in NE-treated
      septic ARVMs was reversed by QVD-OPH, as seen by the increased number of septic
      ARVMs exhibiting caspase-3 fluorescence. Transfection of ARVMs using caspase-3
      siRNA blocked sepsis-induced up-regulation of caspase-3 and increased PS
      following NE treatment. These data suggest that caspase-3 inhibition ameliorated
      sepsis-induced decreased ARVM contractility and blocked the blunted contractile
      response of NE.

PMID- 19394425
TI  - Sequencing and cardiac expression of Apelin in Sus Scrofa.
AB  - In humans, the Apelin gene is located on chromosome Xq25-26.1 and it encodes a 77
      aminoacid prepropeptide. Considerable sequence homology exists across different
      mammalian species. Apelin is emerging as an important regulator of cardiovascular
      homeostasis but, at present, few data from humans are available and further
      studies are necessary to better define its role in cardiovascular
      pathophysiology. The role and function of Apelin in cardiovascular system could
      be reliably investigated in experimental models devoid of confounding effects
      reflecting only the natural history of the disease. The pig constitutes a model
      largely used in experimental pathology where it has a central role in "in vivo"
      clinical settings. Sus Scrofa genoma is not completely sequenced and Apelin gene
      is still lacking. Aim of this study was to sequence the Apelin in Sus Scrofa for
      future applications to molecular biology studies. Using the guanidinium
      thyocyanate-phenol-chloroform method, we extracted total RNA from samples
      obtained from heart of mouse and from atrium and ventricle of normal pigs. Pig
      Apelin mRNA was sequenced using polymerase chain reaction primers designed from
      mouse consensus sequences. A partial sequence of Sus Scrofa Apelin mRNA, 1-201
      pb, was submitted to GenBank (accession number FJ362603). The bands obtained from
      pig cardiac tissue shared a 99% sequence identity with Mus musculus and 90% with
      Rattus norvegicus. The knowledge of Apelin sequence can be an useful starting
      point for future studies devoted to better understand the possible alterations of
      Apelin mRNA expression in different cardiac diseases.

PMID- 19394426
TI  - Knockdown and overexpression of NR1 modulates NMDA receptor function.
AB  - The N-methyl-d-aspartate receptor (NMDAR) is critically involved in learning and
      memory, neuronal survival, as well as neuroexcitotoxicity and seizures. We
      hypothesize that even mild reductions in the numbers of hippocampal NMDARs could
      impair learning and memory, whereas increasing receptor activity would facilitate
      learning but reduce seizure threshold. We developed novel gene transfer
      strategies assisted by an adeno-associated viral vector 1/2 to bi-directionally
      modulate expression levels of the NR1 protein in rat hippocampus. Functional
      consequences of the altered NR1 expression were examined in the acute seizure
      model, and on normal processes of fear memory and neurogenesis. We found that
      knocking down NR1 protected against seizures at the expense of impaired learning,
      as predicted. Paradoxically, NR1 overexpression not only increased fear memory
      and neurogenesis, but also delayed onset of more severe seizures. In conclusion,
      the observed consequences of NR1 knockdown and overexpression underscore NMDAR
      requirement for neuronal plasticity, and are in agreement with its dichotomous
      functions.

PMID- 19394427
TI  - Cytokine-induced SOCS expression is inhibited by cAMP analogue: impact on
      regeneration in injured retina.
AB  - Injured adult retinal ganglion cells (RGCs) regrow axons into peripheral nerve
      (PN) grafted onto cut optic nerve. Survival and regeneration of RGCs is increased
      by intraocular injections of ciliary neurotrophic factor (CNTF) and axonal
      regeneration is further enhanced by co-injection of a cyclic AMP analogue (CPT
      cAMP). Based on these data, and because cytokine signaling is negatively
      regulated by suppressor of cytokine signaling (SOCS) proteins, we set out to
      determine whether CNTF injections increase retinal SOCS expression and whether
      any changes are attenuated by co-injection with CPT-cAMP. Using quantitative PCR
      we found increased SOCS1, SOCS2 and SOCS3 mRNA levels at various times after a
      single CNTF injection. Expression remained high for many days. SOCS protein
      levels were also increased. In situ hybridization revealed that RGCs express
      SOCS3 mRNA, and SOCS expression in cultured RGCs was increased by CNTF. Co
      injection of CPT-cAMP reduced CNTF induced expression of SOCS1 and SOCS3 mRNA and
      decreased SOCS3 protein expression. CNTF injection also transiently increased
      retinal leukemia inhibitory factor (LIF) expression, an effect that was also
      moderated by CPT-cAMP. We propose that, along with known reparative effects of
      elevated cAMP on neurons, reducing SOCS upregulation may be an additional way in
      which cyclic nucleotides augment cytokine-induced regenerative responses in the
      injured CNS.

PMID- 19394429
TI  - Tenascin-C stimulates contactin-dependent neurite outgrowth via activation of
      phospholipase C.
AB  - Tenascin-C (Tnc) is transiently expressed during neural development. Within its
      alternatively spliced fibronectin type III (TNfn) -motifs the TNfnD domain is
      crucial for a neurite outgrowth-promoting region that is recognized by the GPI
      linked adhesion molecule of the Ig-superfamily contactin. In order to understand
      the downstream signaling mechanisms, embryonic day E18 rat hippocampal neurons
      were cultivated on TNfnBD-containing and control substrates in the presence of
      various inhibitors. As predicted, axon outgrowth promotion could be suppressed by
      antibodies to the TNfnD domain, to contactin, or to the beta1-integrin subunit.
      The chelators BAPTA/AM or EGTA as well as blockade of membrane-based calcium
      channels or of the release of calcium from intracellular stores reduced axon
      growth to control levels. The inhibition of phospholipase C and its downstream
      targets protein kinase C or calmodulin kinase likewise blocked outgrowth
      promotion. We propose that TNfnBD stimulates the outgrowth of hippocampal neurons
      by activating calcium- and phospholipase C-depending pathways. Digital video
      microscopy studies revealed that increase of fiber length was caused by an
      augmentation of growth cone velocity.

PMID- 19394430
TI  - Regional mutagenesis using Dissociation in maize.
AB  - We describe genetic screens, molecular methods and web resources newly available
      to utilize Dissociation (Ds) as an insertional mutagen in maize. Over 1700 Ds
      elements have been distributed throughout the maize genome to serve as donor
      elements for local or regional mutagenesis. Two genetic screens are described to
      identify Ds insertions in genes-of-interest (goi). In scheme I, Ds is used to
      generate insertion alleles when a recessive reference allele is available. A Ds
      insertion will enable the cloning of the target gene and can be used to create an
      allelic series. In scheme II, Ds insertions in a goi are identified using a PCR
      based screen to identify the rare insertion alleles among a population of
      testcross progeny. We detail an inverse PCR protocol to rapidly amplify sequences
      flanking Ds insertion alleles and describe a high-throughput 96-well plate-based
      DNA extraction method for the recovery of high-quality genomic DNA from seedling
      tissues. We also describe several web-based tools for browsing, searching and
      accessing the genetic materials described. The development of these Ds insertion
      lines promises to greatly accelerate functional genomics studies in maize.

PMID- 19394428
TI  - A central role for the small GTPase Rac1 in hippocampal plasticity and spatial
      learning and memory.
AB  - Rac1 is a member of the Rho family of small GTPases that are important for
      structural aspects of the mature neuronal synapse including basal spine density
      and shape, activity-dependent spine enlargement, and AMPA receptor clustering in
      vitro. Here we demonstrate that selective elimination of Rac1 in excitatory
      neurons in the forebrain in vivo not only affects spine structure, but also
      impairs synaptic plasticity in the hippocampus with consequent defects in
      hippocampus-dependent spatial learning. Furthermore, Rac1 mutants display
      deficits in working/episodic-like memory in the delayed matching-to-place (DMP)
      task suggesting that Rac1 is a central regulator of rapid encoding of novel
      spatial information in vivo.

PMID- 19394431
TI  - Phylogenetic and morphometric differentiation reveal geographic radiation and
      pseudo-cryptic speciation in a mangrove crab from the Indo-West Pacific.
AB  - The presence of boundaries to dispersal has been recently documented for many
      Indo-West Pacific (IWP) species with planktonic propagules and a widespread
      distribution. We studied the phylogeography of the mangrove crab Neosarmatium
      meinerti (Brachyura: Sesarmidae) and the phylogenetic relationship to its
      presumed sister species N. fourmanoiri in the IWP in order to compare
      intraspecific with interspecific diversity. Portions of the mitochondrial genes
      16S and CoxI were sequenced for 23 specimens of N. meinerti and 5 N. fourmanoiri,
      while a fragment of the 28S was obtained for a subset of specimens. Genetic data
      are supplemented by morphometric and based on 37 adult males of N. meinerti and 9
      males of N. fourmanoiri. The conserved nuclear 28S reveals the existence of a
      genetic break between the Indian and Pacific oceans. Otherwise, mitochondrial
      genes as well as morphometry clearly support the presence of a species complex
      within N. meinerti composed by four well structured and geographically defined
      lineages: East African coast; western Indian Ocean islands; South East Asia; and
      Australia.

PMID- 19394432
TI  - Molecular phylogenetics and generic assessment in the tribe Morindeae (Rubiaceae
      Rubioideae): how to circumscribe Morinda L. to be monophyletic?
AB  - Most of the species of the family Rubiaceae with flowers arranged in head
      inflorescences are currently classified in three distantly related tribes,
      Naucleeae (subfamily Cinchonoideae) and Morindeae and Schradereae (subfamily
      Rubioideae). Within Morindeae the type genus Morinda is traditionally and
      currently circumscribed based on its head inflorescences and syncarpous fruits
      (syncarps). These characters are also present in some members of its allied
      genera, raising doubts about the monophyly of Morinda. We perform Bayesian
      phylogenetic analyses using combined nrETS/nrITS/trnT-F data for 67 Morindeae
      taxa and five outgroups from the closely related tribes Mitchelleae and
      Gaertnereae to rigorously test the monophyly of Morinda as currently delimited
      and assess the phylogenetic value of head inflorescences and syncarps in Morinda
      and Morindeae and to evaluate generic relationships and limits in Morindeae. Our
      analyses demonstrate that head inflorescences and syncarps in Morinda and
      Morindeae are evolutionarily labile. Morinda is highly paraphyletic, unless the
      genera Coelospermum, Gynochthodes, Pogonolobus, and Sarcopygme are also included.
      Morindeae comprises four well-supported and morphologically distinct major
      lineages: Appunia clade, Morinda clade (including Sarcopygme and the lectotype M.
      royoc), Coelospermum clade (containing Pogonolobus and Morinda reticulata), and
      Gynochthodes-Morinda clade. Four possible alternatives for revising generic
      boundaries are presented to establish monophyletic units. We favor the
      recognition of the four major lineages of Morindeae as separate genera, because
      this classification reflects the occurrence of a considerable morphological
      diversity in the tribe and the phylogenetic and taxonomic distinctness of its
      newly delimited genera.

PMID- 19394433
TI  - Effects of prolonged iron overload and low frequency electromagnetic exposure on
      spatial learning and memory in the young rat.
AB  - Low-frequency electromagnetic fields (EMF) have been suggested to affect the
      brain via alterations of blood-brain barrier permeability to iron. Because of an
      immature blood-brain barrier, the young brain may be particularly vulnerable to
      EMF exposure. It is therefore possible that behavioral and neurotoxic effects
      resulting from EMF-induced iron excess in the brain would be greater in young
      adults. The objective of the present study was to investigate the interaction
      between low-frequency EMF and iron overload in young rats. In Experiment 1, we
      tested the effects of iron overload on spatial learning and memory. Iron
      treatment did not affect performance in a reference (Morris water maze) and a
      working memory task (8-arm radial maze). In contrast, detection of a spatial
      change in an object exploration task was impaired. These effects correlated with
      modifications of the serotoninergic metabolism. In Experiment 2, the combination
      of EMF exposure and iron overload was tested. As in Experiment 1, rats were not
      impaired in reference and working memory tasks but were mildly impaired in the
      detection of the spatial change. Overall, the results showed an effect of iron
      overload on spontaneous spatial memory processes. However, low-frequency EMF
      exposure did not potentiate the effects of iron overload in young rats.

PMID- 19394434
TI  - CCR5 deficiency induces astrocyte activation, Abeta deposit and impaired memory
      function.
AB  - Activation of astrocytes has been known to be associated with amyloid-beta
      (Abeta) deposit and production of pro-inflammatory cytokines and chemokines that
      lead to neuronal cell death in the pathogenesis of Alzheimer disease (AD). In the
      present study, we investigated whether the absence of CC chemokine receptor 5
      (CCR5) results in activation of astrocytes, Abeta deposit and memory dysfunction
      in CCR5 knock (CCR5(-/-)) out mice. We found that long-term and spatial memory
      functions were impaired in CCR5(-/-) mice. There was a significant increased
      expression of glial fibrillary acidic protein (GFAP) in the brain of CCR5(-/-)
      mice as compared with that of wild type of CCR5 (CCR5(+/+)) mice. The expression
      of CCR5 was observed in CCR5(+/+) astrocytes, but was reduced in the CCR5(-/-)
      astrocytes even though the expression of GFAP was much higher. Paralleling with
      the activation of astorcytes, the Abeta(1-42) level was higher in the brains of
      CCR5(-/-) mice than that of CCR5(+/+) mice. Expression of beta-secretase (BACE1)
      and its product C99 was significantly elevated in CCR5(-/-) mice. The activation
      of CC chemokine receptor 2 (CCR2) causes activation of astrocytes that leads to
      Abeta deposit and memory dysfunction in CCR5(-/-) mice. In CCR5(-/-) mice, CCR2
      expression was high and co-localized with GFAP. These findings suggest that the
      absence of CCR5 increases expression of CCR2, which leads to the activation of
      astrocytes causing Abeta deposit, and thereby impairs memory function. These
      results suggest that CCR5 may be a critical suppressor of the development and
      progression of AD pathology.

PMID- 19394435
TI  - Enzymatic activity of alpha-L-fucosidase and L-fucokinase across vertebrate
      animal species.
AB  - The oligosaccharide portion of glycoproteins is known to modulate protein
      structure, function, and turnover. Our laboratory is interested in the metabolism
      of L-fucose, a normal constituent of eukaryotic glycoproteins. L-fucose is unique
      in that it is the only levorotatory sugar utilized in mammalian systems. There is
      considerable interest in understanding the controls which determine the level of
      L-fucose attached to proteins, in order to generate stable and active glycoforms
      of protein for the treatment of disease. As part of a program to determine the
      controls on protein L-fucosylation, we have systematically determined the tissue
      distribution of the enzymes L-fucokinase and alpha-L-fucosidase in species across
      the vertebrate animal kingdom. In general, the level of alpha-L-fucosidase is
      higher than L-fucokinase level. The tissue with highest enzyme activity cannot be
      generalized, regardless of which enzyme is of interest. Furthermore, there is not
      a correlation between synthetic and catabolic enzyme activity within a tissue. L
      fucokinase can be detected in all tissues examined. Interestingly, we have also
      detected ss-D-fucosidase activity, present in extraordinary levels in the liver
      and small intestine of snake. Whether this is due to a specific enzyme or whether
      it represents a broad specificity of the alpha-L-fucosidase is currently being
      investigated.

PMID- 19394437
TI  - Experimental infections with the tropical monogenean, Gyrodactylus bullatarudis:
      potential invader or experimental fluke?
AB  - Introduced exotic species have the potential to spread their associated parasites
      to native species which can be catastrophic if these hosts are immunologically
      naive to the novel parasite. The guppy (Poecilia reticulata) has been
      disseminated worldwide outside of its native habitat and therefore could be an
      important source of infection to native fish species. Its parasite fauna is
      dominated by the ectoparasitic monogeneans, Gyrodactylus turnbulli and
      Gyrodactylus bullatarudis. The current study tested the host specificity of G.
      bullatarudis by experimentally infecting a range of isolated fish hosts,
      including temperate species. Surprisingly, the parasite was capable of
      establishing and reproducing, for several days, on the three-spined stickleback
      when transferred directly to this host. We also established that G. bullatarudis
      could be transmitted under aquarium conditions at both 25 degrees C and 15
      degrees C. At the higher temperature, the parasite was even capable of
      reproducing on this atypical host. The implications of these findings are
      discussed in terms of host specificity, host switching and climate change.

PMID- 19394438
TI  - Plant PA signaling via diacylglycerol kinase.
AB  - Accumulating evidence suggests that phosphatidic acid (PA) plays a pivotal role
      in the plant's response to environmental signals. Besides phospholipase D (PLD)
      activity, PA can also be generated by diacylglycerol kinase (DGK). To establish
      which metabolic route is activated, a differential (32)P-radiolabelling protocol
      can be used. Based on this, and more recently on reverse-genetic approaches, DGK
      has taken center stage, next to PLD, as a generator of PA in biotic and abiotic
      stress responses. The DAG substrate is generally thought to be derived from PI
      PLC activity. The model plant system Arabidopsis thaliana has 7 DGK isozymes, two
      of which, AtDGK1 and AtDGK2, resemble mammalian DGKepsilon, containing a
      conserved kinase domain, a transmembrane domain and two C1 domains. The other
      ones have a much simpler structure, lacking the C1 domains, not matched in
      animals. Several protein targets have now been discovered that bind PA. Whether
      the PA molecules engaged in these interactions come from PLD or DGK remains to be
      elucidated.

PMID- 19394439
TI  - Does anthropogenic metal pollution affect carotenoid colouration, antioxidative
      capacity and physiological condition of great tits (Parus major)?
AB  - Although several studies have shown that carotenoid-based signals are negatively
      affected by (metal) pollution, the underlying mechanisms are not well understood.
      There are two possible, not mutually exclusive, hypotheses to explain the metal
      induced fading of carotenoid colouration. Metal pollution could affect oxidative
      stress levels and/or the diet. We assessed the expression of the yellow breast of
      adult and nestling great tits (Parus major) and related this to physiological
      parameters in plasma indicative of oxidative stress (total antioxidative
      capacity) and nutritional condition (albumin, triglyceride, total protein,
      cholesterol and uric acid concentrations). In four study sites along a metal
      pollution gradient, both adult and nestling great tits had significantly reduced
      carotenoid colouration at the most polluted sites. While nestlings' total
      antioxidative capacity was significantly affected by metal pollution, there was
      no significant effect on adults' total antioxidative capacity. Both for adult and
      nestling birds, no clear relation between total antioxidative capacity and
      carotenoid colouration was found. However, there were significant differences
      among sites in nutritional parameters, indicating that metal pollution might
      affect diet composition and quality. We found strong among brood variation in
      nestlings for all variables (except cholesterol), suggesting that there might be
      a considerable genetic and/or parental investment factor involved.

PMID- 19394436
TI  - Multi-scale mechanics from molecules to morphogenesis.
AB  - Dynamic mechanical processes shape the embryo and organs during development.
      Little is understood about the basic physics of these processes, what forces are
      generated, or how tissues resist or guide those forces during morphogenesis. This
      review offers an outline of some of the basic principles of biomechanics,
      provides working examples of biomechanical analyses of developing embryos, and
      reviews the role of structural proteins in establishing and maintaining the
      mechanical properties of embryonic tissues. Drawing on examples we highlight the
      importance of investigating mechanics at multiple scales from milliseconds to
      hours and from individual molecules to whole embryos. Lastly, we pose a series of
      questions that will need to be addressed if we are to understand the larger
      integration of molecular and physical mechanical processes during morphogenesis
      and organogenesis.

PMID- 19394440
TI  - A graph-based approach to auditing RxNorm.
AB  - OBJECTIVES: RxNorm is a standardized nomenclature for clinical drug entities
      developed by the National Library of Medicine. In this paper, we audit relations
      in RxNorm for consistency and completeness through the systematic analysis of the
      graph of its concepts and relationships. METHODS: The representation of multi
      ingredient drugs is normalized in order to make it compatible with that of single
      ingredient drugs. All meaningful paths between two nodes in the type graph are
      computed and instantiated. Alternate paths are automatically compared and
      manually inspected in case of inconsistency. RESULTS: The 115 meaningful paths
      identified in the type graph can be grouped into 28 groups with respect to start
      and end nodes. Of the 19 groups of alternate paths (i.e., with two or more paths)
      between the start and end nodes, 9 (47%) exhibit inconsistencies. Overall, 28
      (24%) of the 115 paths are inconsistent with other alternate paths. A total of
      348 inconsistencies were identified in the April 2008 version of RxNorm and
      reported to the RxNorm team, of which 215 (62%) had been corrected in the January
      2009 version of RxNorm. CONCLUSION: The inconsistencies identified involve
      missing nodes (93), missing links (17), extraneous links (237) and one case of
      mix-up between two ingredients. Our auditing method proved effective in
      identifying a limited number of errors that had defeated the quality assurance
      mechanisms currently in place in the RxNorm production system. Some
      recommendations for the development of RxNorm are provided.

PMID- 19394442
TI  - Simultaneous occurrence of obscure-overt gastrointestinal and intraperitoneal
      bleeding in gastrointestinal stromal tumor.

PMID- 19394443
TI  - Gastric emptying.

PMID- 19394441
TI  - Use of over-the-counter analgesics is not associated with acute decompensation in
      patients with cirrhosis.
AB  - BACKGROUND & AIMS: Over-the-counter analgesics have been proposed to lead to
      decompensation of compensated cirrhosis or to further decompensation of an
      already decompensated patient. We performed a prospective, case-control study to
      investigate the effects of analgesics on acute hepatic decompensation. METHODS:
      Data from consecutive cirrhotic patients hospitalized at 2 tertiary care
      hospitals for decompensation of cirrhosis (cases, n = 91) were compared with that
      from consecutive patients with compensated cirrhosis that were followed in the
      liver clinic (n = 153) and with randomly selected noncirrhotic patients
      concurrently hospitalized with the cases (n = 89). All patients were given a
      structured questionnaire to collect information on recent use of acetaminophen,
      nonsteroidal anti-inflammatory drugs and alcohol. RESULTS: Only 32 (35%) of the
      cirrhotic patients used over-the-counter analgesics (19% acetaminophen, 16%
      nonsteroidal anti-inflammatory drugs), compared with 80 of the cirrhotic controls
      (52%; 25% acetaminophen, 31% nonsteroidal anti-inflammatory drugs), and 62 (70%)
      of the noncirrhotic controls. Acetaminophen use did not differ between groups,
      even for those with recent alcohol use. The doses and days of nonsteroidal anti
      inflammatory drug use were higher among cirrhotic patients, compared with
      controls. Alcohol ingestion was significantly greater among patients with
      alcoholic cirrhosis, compared with controls. CONCLUSIONS: In patients with
      cirrhosis, acetaminophen use at doses lower than those recommended is not
      associated with acute hepatic decompensation, even in patients with recent
      alcohol ingestion. Nonsteroidal anti-inflammatory drugs might be associated with
      deleterious effects on cirrhosis. Alcohol ingestion is associated with
      decompensation in patients with alcoholic cirrhosis.

PMID- 19394444
TI  - Tone the bones of your chronic liver disease patients.

PMID- 19394445
TI  - Development of hepatocellular carcinoma after seroclearance of hepatitis B
      surface antigen.
AB  - BACKGROUND & AIMS: During the natural course of chronic hepatitis B virus
      infection, a small proportion of patients experience hepatitis B surface antigen
      (HBsAg) seroclearance. However, the long-term clinical outcomes of this process
      are not well established. METHODS: Thirty-five patients with chronic hepatitis B,
      followed between 1976 and 2008 at a community liver clinic, experienced HBsAg
      seroclearance. Ten patients were Caucasian and 25 were Asian. These patients
      continued to undergo surveillance for hepatocellular carcinoma that included test
      for alpha-fetoprotein levels and abdominal ultrasound examinations. The median
      follow-up time was 185 months (range, 27-400 months). RESULTS: During the initial
      visit to the clinic, the median age of the patients was 41 years (range, 1.5-72
      years). Eighteen patients (51.4%) were hepatitis B e antigen (HBeAg) positive 25
      (71.4%) were hepatitis B virus DNA positive, and 13 (37.1%) had cirrhosis. At the
      time of HBsAg loss, the median age was 54 years (range, 13-77 years) and all were
      hepatitis B e antigen- as well as hepatitis B virus DNA negative. During the long
      term follow-up, 4 patients with cirrhosis developed hepatocellular carcinoma
      (HCC), which was discovered by ultrasound examination. Factors associated with
      development of HCC were low baseline levels of albumin (P = .04), family
      histories of HBsAg positivity (P = .01) and HCC (P = .04), and age of less than
      50 years at the time of HBsAg clearance (P = .03). CONCLUSIONS: HCC can still
      develop after HBsAg seroclearance. Thus, surveillance should be continued after
      HBsAg loss in the same manner as for HBsAg positive patients.

PMID- 19394446
TI  - Diagnostic value of colonoscopy in intestinal Diphyllobothrium latum infection.

PMID- 19394447
TI  - A case of an unsuspected cause of Budd-Chiari syndrome.

PMID- 19394448
TI  - Recruitment of breast cancer survivors into a 12-month supervised exercise
      intervention is feasible.
AB  - BACKGROUND: The BREX study is one of the largest randomised prospective exercise
      interventions of breast cancer survivors which aims at investigate whether
      regular exercise could reduce the long-term side effects of the adjuvant
      treatments and improve quality of life. MATERIAL AND METHODS: The study was
      limited to consider patients aged 35-68 years, who had recently completed
      adjuvant chemotherapy or started endocrine therapy. In this paper, we describe
      the recruitment process of the 413 randomised patients from the Helsinki
      University Hospital between September 2005 and September 2007. RESULTS: 768
      potentially eligible patients out of the 1321 screened (via medical records) were
      contacted by phone. After the phone call 240 patients were excluded due to health
      problems that contraindicated exercise training. The most common health problems
      were musculoskeletal disorders. A total of 528 patients were considered as
      eligible for the intervention. Ultimately 413 of them agreed to participate
      resulting in a 53.8% recruitment rate of the potentially eligible patients. The
      most important reasons for declining were social, not health related. Eligible
      patients who did not want to participate did not differ significantly from those
      who participated according to age, health status, breast cancer treatment and
      tumour type. DISCUSSION: The high recruitment rate demonstrates breast cancer
      patient's willingness to participate even in long-lasting supervised exercise
      programs shortly after adjuvant treatments. After taking into account the
      selection of the population by age and musculoskeletal health, the results of the
      present intervention can be generalized to represent urban breast cancer patient
      population in Finland.

PMID- 19394449
TI  - The novel G10680A mutation is associated with complete penetrance of the
      LHON/T14484C family.
AB  - We report the clinical and genetic characterization of a Chinese Leber's
      hereditary optic neuropathy (LHON) family with complete penetrance and high
      percentage of recovery. Sequence analysis of the complete mitochondrial DNA
      revealed the presence of heteroplasmic ND6/T14484C mutation and 27 other
      variants, belonging to the East-Asian haplogroup B4b'd. Of those variants, a
      novel homoplasmic G10680A mutation substituted a threonine for a highly conserved
      alanine at ND4L amino acid 71, which was not found in unaffected family members
      and 100 normal controls. It indicated that G10680A may play a synergistic role
      with the primary mutation T14484C, leading to the complete penetrance of LHON in
      the presenting family. In addition, the other modifier factors including nuclear
      background, mitochondrial haplotypes and other environmental factors should
      account for the phenotypic variability of visual impairment in this family.

PMID- 19394451
TI  - Partial liquid ventilation confers protection against acute lung injury induced
      by endotoxin in juvenile piglets.
AB  - To investigate the effect of partial liquid ventilation (PLV) at low inflation
      pressures on acute lung injury (ALI), endotoxin was administered to healthy
      anesthetized juvenile piglets. The animals were randomly assigned to two groups,
      n=6 each: (1) conventional mechanical ventilation (MV) and (2) PLV with
      perfluorodecalin (10 mL kg(-1)). Compared with MV, PLV improved each
      cardiopulmonary variable measured. These variables included pulse contour cardiac
      output, heart rate, blood pH, breathing rate, both partial pressure of arterial
      oxygen (PaO2) and PaO2/FIO2 (fraction of inspired oxygen), partial pressure of
      arterial carbon dioxide (PaCO2), dynamic lung compliance, tidal volume, and
      ventilation efficacy index. Lung morphology also showed less damage in the PLV
      group, even in non-dependent regions (P<0.05). Our data support the hypothesis
      that PLV can decrease pulmonary damage, improve gas exchange and cardiac output,
      and may lead to a better prognosis in endotoxin-induced ALI.

PMID- 19394450
TI  - Medullary serotonin neurons and central CO2 chemoreception.
AB  - Serotonergic (5-HT) neurons are putative central respiratory chemoreceptors,
      aiding in the brain's ability to detect arterial changes in PCO2 and implement
      appropriate ventilatory responses to maintain blood homeostasis. These neurons
      are in close proximity to large medullary arteries and are intrinsically
      chemosensitive in vitro, characteristics expected for chemoreceptors. 5-HT
      neurons of the medullary raphe are stimulated by hypercapnia in vivo, and their
      disruption results in a blunted hypercapnic ventilatory response. More recently,
      data collected from transgenic and knockout mice have provided further insight
      into the role of 5-HT in chemosensitivity. This review summarizes current
      evidence in support of the hypothesis that 5-HT neurons are central
      chemoreceptors, and addresses arguments made against this role. We also briefly
      explore the relationship between the medullary raphe and another chemoreceptive
      site, the retrotrapezoid nucleus, and discuss how they may interact during
      hypercapnia to produce a robust ventilatory response.

PMID- 19394453
TI  - L-carbocisteine reduces neutrophil elastase-induced mucin production.
AB  - Human neutrophil elastase (HNE) exists in high concentrations in airway
      secretions and produces mucus hypersecretion in patients with chronic obstructive
      pulmonary disease (COPD). L-carbocisteine improves the quality of life and
      reduces exacerbation in COPD patients. However the precise mechanism is
      uncertain. We examined the effects of L-carbocisteine on HNE-induced mucus
      hypersecretion and on the production of reactive oxygen species (ROS) which is
      associated with mucin production induced by HNE. NCI-H292, a human lung
      mucoepidermoid carcinoma cell line, was treated with or without HNE and L
      carbocisteine. MUC5AC mRNA expression and ROS production in the cells, and MUC5AC
      protein concentration in supernatants were measured. HNE increased MUC5AC mRNA
      expression and MUC5AC protein concentration in supernatants in the cells. L
      carbocisteine reduces HNE-induced mRNA expression and protein secretion of
      MUC5AC. L-carbocisteine also reduced ROS production in the cells induced by HNE.
      Reduction of HNE-induced mucus secretion by L-carbocisteine in the pulmonary
      epithelial cells may partly relate to the reduction of ROS.

PMID- 19394452
TI  - Breathing disorders in Rett syndrome: progressive neurochemical dysfunction in
      the respiratory network after birth.
AB  - Disorders of respiratory control are a prominent feature of Rett syndrome (RTT),
      a severely debilitating condition caused by mutations in the gene encoding methyl
      CpG-binding protein 2 (MECP2). RTT patients present with a complex respiratory
      phenotype that can include periods of hyperventilation, apnea, breath holds
      terminated by Valsalva maneuvers, forced and deep breathing and apneustic
      breathing, as well as abnormalities of heart rate control and cardiorespiratory
      integration. Recent studies of mouse models of RTT have begun to shed light on
      neurologic deficits that likely contribute to respiratory dysfunction including,
      in particular, defects in neurochemical signaling resulting from abnormal
      patterns of neurotransmitter and neuromodulator expression. The authors
      hypothesize that breathing dysregulation in RTT results from disturbances in
      mechanisms that modulate the respiratory rhythm, acting either alone or in
      combination with more subtle disturbances in rhythm and pattern generation. This
      article reviews the evidence underlying this hypothesis as well as recent efforts
      to translate our emerging understanding of neurochemical defects in mouse models
      of RTT into preclinical trials of potential treatments for respiratory
      dysfunction in this disease.

PMID- 19394454
TI  - Ethnic differences in parathyroid hormone secretion and mineral metabolism in
      response to oral phosphate administration.
AB  - Ethnic differences in bone metabolism have been reported and it has been
      suggested that these may be partly due to prolonged exposure to an elevated
      plasma parathyroid hormone (PTH) concentration or a decreased sensitivity to PTH.
      We explored ethnic differences in bone and mineral metabolism by 5 days of oral
      phosphate (P) loading to stimulate PTH secretion. Healthy older people from UK
      (B), The Gambia (G) and China (C), 15 individuals from each sex and ethnic group,
      were studied. Blood and urine samples were collected before and 2 h after P dose
      on days 1, 4 and 5 and on a control day. The induced changes (%) in PTH and
      markers of mineral and bone metabolism after 2 h and over 5 days were examined.
      At baseline, PTH, 1,25(OH)(2)D and bone turnover markers were higher in Gambian
      subjects than in British and Chinese subjects (P < or = 0.01). 2 h after P
      loading, ionized calcium (iCa) decreased and PTH and plasma P (P) increased in
      all groups (P < or = 0.01, n.s. between groups). Urinary P to creatinine ratio
      (uP/Cr) increased, the increase being greater in Chinese subjects than in British
      and Gambian subjects on days 4 and 5 (P < or = 0.01). By day 5, fasting iCa was
      decreased and P increased in British and Gambian (P < or = 0.01) but not in
      Chinese subjects. Fasting PTH and uP/Cr increased in all groups. There were
      ethnic differences in changes in bone markers, but the relationship with changes
      in PTH was comparable between groups. In conclusion, ethnic differences in
      mineral metabolism in response to 5-day P loading were found. Chinese subjects
      showed a more rapid renal clearance of P than British and Gambian counterparts
      and there were differences between the groups in the skeletal response to P
      loading, but no evidence was found for resistance to the resorbing effects of
      PTH.

PMID- 19394455
TI  - Race and sex differences in bone mineral density and geometry at the femur.
AB  - INTRODUCTION: Differences in osteoporotic hip fracture incidence between American
      whites and blacks and between women and men are considered to result, in part,
      from differences in bone mineral density and geometry at the femur. The aim of
      this study was to quantify differences in femoral bone density and geometry
      between a large sample of healthy American white and black women and men.
      SUBJECTS AND METHODS: Healthy American white (n=612) and black (n=164)
      premenopausal women, aged 23 to 57 years, and healthy American white (n=492) and
      black (n=169) men, aged 20 to 63 years, had volumetric bone mineral density
      (vBMD) and geometry variables measured at the femur by computerized tomography
      (CT), and areal bone mineral density (aBMD) at femoral neck measured by dual X
      ray absorptiometry (DXA). RESULTS: American blacks had higher vBMD at the femoral
      neck and femoral shaft cortex than American whites whereas femoral axis length
      and femoral neck area were not different. Men had lower vBMD at the femoral neck
      and femoral cortex than women but had greater femoral axis length and femoral
      neck area than women. The higher aBMD in American blacks than whites persisted
      after correction for measured area whereas the higher aBMD in men than women
      disappeared. CONCLUSIONS: At the femoral neck, American whites have lower bone
      density than American blacks but similar geometry. Women have higher bone density
      than men in both races but have smaller geometry variables. The differences in
      bone density may account in part for the differences in hip fracture incidence
      between American blacks and whites, whereas the differences in femur size may
      account for the differences in hip fracture rates between men and women.

PMID- 19394456
TI  - Prevalence and risk factors of low bone mineral density and 25-hydroxyvitamin D
      status in young healthy epileptic adult patients in a tropical Asian country
      taking antiepileptic drug.
AB  - PURPOSE: Antiepileptic drugs have been reported to reduce bone mineral density
      (BMD) in several countries with varying prevalence but in studies with small
      sample size and inadequate assessment of confounders, and rarely including young
      adults. We sought to determine the prevalence, vitamin D status and risk factors
      for low BMD in young adult epileptic patients in a tropical setting. METHODS: We
      prospectively examined left femoral neck and spine with dual-energy X-ray
      absorption. Demographic data, basic laboratory studies, history of clinical
      epilepsy, parathyroid hormone and vitamin D level were obtained. RESULTS: One
      hundred and twenty three patients were included. The mean (+/-SD) T-score was 
      0.31+/-1.24 at the spine and -0.19+/-1.11 at the left femoral neck. 36% had
      osteopenia and 4.1% had osteoporosis at either site. Four patients had vitamin D
      deficiency. Vitamin D levels were not correlated with BMD. Twenty-five patients
      had vitamin D insufficiency. Multivariate logistic regression analysis identified
      low body mass index (BMI) and male sex as risk factors for low BMD at the spine
      and low BMI and duration of treatment as risk factors for low BMD at the left
      femoral neck. CONCLUSION: Chronic use of antiepileptic drug (AED) in young adult
      patients is associated with low BMD.

PMID- 19394458
TI  - Dietary sources of nutrients preferred.

PMID- 19394459
TI  - Now is our time.

PMID- 19394462
TI  - A guide to greener meetings.

PMID- 19394463
TI  - PPW goes online and carries message of advocacy throughout the year.

PMID- 19394464
TI  - Organic vs conventional farming.

PMID- 19394465
TI  - Opportunities with US Public Health Service.

PMID- 19394466
TI  - Closing the gap between calcium intake and requirements.

PMID- 19394467
TI  - Lower-energy-density diets are associated with higher monetary costs per
      kilocalorie and are consumed by women of higher socioeconomic status.
AB  - OBJECTIVE: Diets of lower energy density are associated with higher diet quality,
      lower body weights, and better health outcomes. This study examined associations
      among dietary energy density, energy-adjusted diet costs, and socioeconomic
      indicators of study participants. DESIGN: In this cross-sectional study, energy
      and nutrient intakes for 164 men and women aged 25 to 65 years were obtained
      using a food frequency instrument between June 2005 and September 2006. Dietary
      energy density (kcal/g) was calculated with and without beverages. Energy
      adjusted diet costs ($/2,000 kcal) were calculated using food prices in Seattle,
      WA. Tertile splits of energy density and energy cost were analyzed using tests
      for linear trend. Linear regression models tested the association between
      education, income, and dietary variables, adjusting for age and sex. RESULTS:
      Diets of lower energy density were associated with higher absolute nutrient
      intakes. Diets of lower energy density were also associated with higher energy
      adjusted diet costs. Conversely, highest energy density diets were associated
      with lower intakes of micronutrients and fiber and lower costs. Education and
      household income showed a negative association with dietary energy density in
      regression models. Education and household incomes showed a positive association
      with the energy-adjusted cost of the diet. Education was a stronger predictor of
      both energy density and energy cost than was household income. CONCLUSIONS:
      Higher-quality diets were not only more costly per kilocalorie but were also
      consumed by persons of higher educational level. The influence of diet quality on
      health, observed in some epidemiologic studies, might be modulated by unobserved
      indexes of socioeconomic status.

PMID- 19394468
TI  - Sociodemographic differences in selected eating practices among alternative high
      school students.
AB  - BACKGROUND: Students attending alternative high schools are an at-risk group of
      youth for poor health behaviors and obesity. However, little is known about their
      dietary practices. OBJECTIVE: To examine associations between sex,
      race/ethnicity, and socioeconomic status and selected dietary practices,
      including consumption of sugar-sweetened beverages, high-fat foods, and fruits
      and vegetables and fast-food restaurant use, among students attending alternative
      high schools. DESIGN: Population-based, cross-sectional study. SUBJECTS/SETTING:
      A convenience sample of adolescents (n=145; 52% men; 63% aged <18 years; and 39%
      white, 32% African American, and 29% other/multiracial) attending six alternative
      high schools in the St Paul/Minneapolis, MN, metropolitan area completed a
      survey. Students were participants in the Team COOL (Controlling Overweight and
      Obesity for Life) pilot study, a group randomized obesity prevention trial.
      STATISTICAL ANALYSES PERFORMED: Descriptive statistics were used to describe
      dietary practices. Mixed model multivariate analyses were used to assess
      differences in dietary practices by sex, race/ethnicity, and socioeconomic
      status. RESULTS: Regular soda was consumed at least five to six times per week by
      more than half of students. One half of students reported eating or drinking
      something from a fast-food restaurant at least three to four times a week.
      African-American students had the highest consumption of sugar-sweetened
      beverages (P=0.025), high-fat foods (P=0.002), and highest frequency of fast-food
      restaurant use (P<0.025). Mean fruit/vegetable intake was 3.6 servings/day; there
      were no sociodemographic differences in fruit/vegetable consumption. Higher
      socioeconomic status was associated with a higher consumption of regular soda
      (P=0.027). CONCLUSIONS: Racial/ethnic and sex differences in the consumption of
      regular soda, high-fat foods, and fast-food restaurant use among alternative high
      school students underscores the importance of implementing health promotion
      programs in alternative high schools.

PMID- 19394469
TI  - Calcium absorption from fortified ice cream formulations compared with calcium
      absorption from milk.
AB  - OBJECTIVE: Optimal bone mass in early adulthood is achieved through appropriate
      diet and lifestyle, thereby protecting against osteoporosis and risk of bone
      fracture in later life. Calcium and vitamin D are essential to build adequate
      bones, but calcium intakes of many population groups do not meet dietary
      reference values. In addition, changes in dietary patterns are exacerbating the
      problem, thereby emphasizing the important role of calcium-rich food products. We
      have designed a calcium-fortified ice cream formulation that is lower in fat than
      regular ice cream and could provide a useful source of additional dietary
      calcium. Calcium absorption from two different ice cream formulations was
      determined in young adults and compared with milk. SUBJECTS/SETTING: Sixteen
      healthy volunteers (25 to 45 years of age), recruited from the general public of
      The Netherlands, participated in a randomized, reference-controlled, double-blind
      cross-over study in which two test products and milk were consumed with a light
      standard breakfast on three separate occasions: a standard portion of ice cream
      (60 g) fortified with milk minerals and containing a low level (3%) of butter
      fat, ice cream (60 g) fortified with milk minerals and containing a typical level
      (9%) of coconut oil, and reduced-fat milk (1.7% milk fat) (200 mL). Calcium
      absorption was measured by the dual-label stable isotope technique. STATISTICAL
      ANALYSIS: Effects on calcium absorption were evaluated by analysis of variance.
      RESULTS: Fractional absorption of calcium from the 3% butterfat ice cream, 9%
      coconut oil ice cream, and milk was 26%+/-8%, 28%+/-5%, and 31%+/-9%,
      respectively, and did not differ significantly (P=0.159). CONCLUSIONS: Results
      indicate that calcium bioavailability in the two calcium-fortified ice cream
      formulations used in this study is as high as milk, indicating that ice cream may
      be a good vehicle for delivery of calcium.

PMID- 19394470
TI  - Hand-held indirect calorimeter offers advantages compared with prediction
      equations, in a group of overweight women, to determine resting energy
      expenditures and estimated total energy expenditures during research screening.
AB  - OBJECTIVE: To compare standardized prediction equations to a hand-held indirect
      calorimeter in estimating resting energy and total energy requirements in
      overweight women. DESIGN: Resting energy expenditure (REE) was measured by hand
      held indirect calorimeter and calculated by prediction equations Harris-Benedict,
      Mifflin-St Jeor, World Health Organization/Food and Agriculture
      Organization/United Nations University (WHO), and Dietary Reference Intakes
      (DRI). Physical activity level, assessed by questionnaire, was used to estimate
      total energy expenditure (TEE). SUBJECTS: Subjects (n=39) were female nonsmokers
      older than 25 years of age with body mass index more than 25. STATISTICAL
      ANALYSES: Repeated measures analysis of variance, Bland-Altman plot, and fitted
      regression line of difference. A difference within +/-10% of two methods
      indicated agreement. RESULTS: Significant proportional bias was present between
      hand-held indirect calorimeter and prediction equations for REE and TEE (P<0.01);
      prediction equations overestimated at lower values and underestimated at higher
      values. Mean differences (+/-standard error) for REE and TEE between hand-held
      indirect calorimeter and Harris-Benedict were -5.98+/-46.7 kcal/day (P=0.90) and
      21.40+/-75.7 kcal/day (P=0.78); between hand-held indirect calorimeter and
      Mifflin-St Jeor were 69.93+/-46.7 kcal/day (P=0.14) and 116.44+/-75.9 kcal/day
      (P=0.13); between hand-held indirect calorimeter and WHO were -22.03+/-48.4
      kcal/day (P=0.65) and -15.8+/-77.9 kcal/day (P=0.84); and between hand-held
      indirect calorimeter and DRI were 39.65+/-47.4 kcal/day (P=0.41) and 56.36+/-85.5
      kcal/day (P=0.51). Less than 50% of predictive equation values were within +/-10%
      of hand-held indirect calorimeter values, indicating poor agreement. CONCLUSIONS:
      A significant discrepancy between predicted and measured energy expenditure was
      observed. Further evaluation of hand-held indirect calorimeter research screening
      is needed.

PMID- 19394471
TI  - Fourth-grade children's dietary recall accuracy is influenced by retention
      interval (target period and interview time).
AB  - BACKGROUND: For a 24-hour dietary recall, two possible target periods are the
      prior 24 hours (24 hours immediately preceding the interview time) and previous
      day (midnight to midnight of the day before the interview), and three possible
      interview times are morning, afternoon, and evening. Target period and interview
      time determine the retention interval (elapsed time between to-be-reported meals
      and the interview), which, along with intervening meals, can influence reporting
      accuracy. OBJECTIVE: The effects of target period and interview time on
      children's accuracy for reporting school meals during 24-hour dietary recalls
      were investigated. DESIGN AND SUBJECTS/SETTING: During the 2004-2005, 2005-2006,
      and 2006-2007 school years in Columbia, SC, each of 374 randomly selected fourth
      grade children (96% African American) was observed eating two consecutive school
      meals (breakfast and lunch) and interviewed to obtain a 24-hour dietary recall
      using one of six conditions defined by crossing two target periods with three
      interview times. Each condition had 62 or 64 children (half boys). MAIN OUTCOME
      MEASURES: Accuracy for reporting school meals was quantified by calculating rates
      for omissions (food items observed eaten but unreported) and intrusions (food
      items reported eaten but unobserved); a measure of total inaccuracy combined
      errors for reporting food items and amounts. STATISTICAL ANALYSES PERFORMED: For
      each accuracy measure, analysis of variance was conducted with target period,
      interview time, their interaction, sex, interviewer, and school year in the
      model. RESULTS: There was a target-period effect and a target-period by interview
      time interaction on omission rates, intrusion rates, and total inaccuracy (six P
      values <0.004). For prior-24-hour recalls compared to previous-day recalls, and
      for prior-24-hour recalls in the afternoon and evening compared to previous-day
      recalls in the afternoon and evening, omission rates were better by one third,
      intrusion rates were better by one half, and total inaccuracy was better by one
      third. CONCLUSIONS: To enhance children's dietary recall accuracy, target periods
      and interview times that minimize the retention interval should be chosen.

PMID- 19394472
TI  - Competitive foods in schools: availability and purchasing in predominately rural
      small and large high schools.
AB  - OBJECTIVES: Schools have an important role to play in obesity prevention, but
      little is known about the food environment in small, predominately rural schools.
      The primary purpose of this study was to compare the availability and student
      purchasing of foods sold outside of the reimbursable meals program through a la
      carte or vending (ie, competitive foods) in small (n=7) and large (n=6) Kansas
      high schools. METHODS: A cross-sectional observational study design was used to
      capture the number of a la carte and vending items available and purchased, and
      the fat and energy content of all available and purchased items on a single
      school day between January and May 2005. RESULTS: Small schools had significantly
      fewer vending machines than large schools (median 3.0 [range 2.0 to 5.0] vs 6.5
      [range 4.0 to 8.0], P<0.01]. Vending and a la carte items at small schools
      contained a median of 2.3 fewer fat grams per item (P< or =0.05), whereas vending
      products contained a median of 25 kcal fewer per item (P< or =0.05) than at large
      schools. Significantly less fat (median -15.4 g/student) and less energy (median 
      306.8 kcal/student) were purchased per student from all competitive food sources
      and from a la carte (median -12.9 g fat and -323.3 kcal/student) by students in
      small schools compared to students in large schools (P< or =0.05). CONCLUSIONS:
      The findings, which highlight less availability and lower energy content from
      competitive foods at small compared to large schools, have implications for
      understanding how small schools support their foodservice programs with limited
      dependence on competitive foods and the influence that food and nutrition
      professionals can have on school environments by providing more oversight into
      the nutritional quality of foods available.

PMID- 19394473
TI  - Almonds have a neutral effect on serum lipid profiles: a meta-analysis of
      randomized trials.
AB  - Almond consumption may be associated with improvements in serum lipid profiles.
      The aim was to evaluate the influence of almonds on lipid parameters to help
      define the role of almonds as a lipid modulator. MEDLINE, EMBASE, Cochrane
      CENTRAL, and the Natural Medicines Comprehensive Database were searched through
      July 2008, with no language restrictions, for randomized controlled trials of
      almonds in human patients that reported efficacy data on at least one of the
      following endpoints: total, low-density lipoprotein (LDL), or high-density
      lipoprotein (HDL) cholesterol, triglycerides, or the LDL:HDL ratio. A manual
      search of references from primary or review articles was performed to identify
      additional relevant trials. Five randomized, controlled trials (totaling 142
      participants) met all inclusion criteria. Upon meta-analysis, almond consumption
      ranging from 25 to 168 g/day significantly lowered total cholesterol [weighted
      mean difference -6.95 mg/dL (95% confidence interval [CI] -13.12 to -0.772) (
      0.18 mmol/L [95% CI -0.34 to -0.02])] and showed a strong trend toward reducing
      LDL cholesterol [weighted mean difference -5.79 mg/dL (95% CI -11.2 to 0.00) (
      0.15 mmol/L [95% CI -0.29 to 0.00])]. No significant effect on HDL cholesterol,
      triglycerides, or LDL:HDL ratio was found. No statistical heterogeneity was
      observed for any analysis (I2=0% for all). Review of funnel plots and the Egger's
      weighted regression statistic P values suggested a low likelihood of publication
      bias in all analyses (P>0.25 for all). Almond consumption may decrease total
      cholesterol and does not significantly affect LDL or HDL cholesterol,
      triglycerides, or the LDL:HDL ratio. The current body of randomized trials does
      not support the ingestion of almonds solely for their lipid modifying effects.
      Both the lipid modulating effects and the safety/tolerability of almonds should
      be further investigated through the conduction of larger randomized, double
      blinded trials of longer duration. Such studies might focus specifically on
      whether the efficacy of almonds as a lipid modulator varies by dose or
      comorbidity.

PMID- 19394475
TI  - Availability of more healthful food alternatives in traditional, convenience, and
      nontraditional types of food stores in two rural Texas counties.
AB  - Limited research has focused on the availability of more healthful food
      alternatives in traditional food stores (supermarkets and grocery stores) in
      rural areas. Current market trends suggest that food items may be available for
      purchase in stores other than traditional food stores. An observational survey
      was developed and used on-site to document the availability and variety of fruit
      and vegetables (fresh, canned, and frozen), meats (meat, poultry, fish, and
      eggs), dairy (milk, yogurt, and cheese), and grains (whole grains and refined
      grains) in all traditional food stores, convenience stores, and nontraditional
      food stores (dollar stores and mass merchandisers) in two rural Texas counties.
      Descriptive statistics and t tests identified that although the widest selection
      of more healthful food items was available in supermarkets, not all supermarkets
      carried all items. Grocery stores carried less variety of fresh fruits (8+/-0.7
      vs 4.7+/-0.3; P<0.01) and vegetables (10.7+/-0.2 vs 6+/-0; P<0.001) than
      supermarkets. Fresh fruits and vegetables were not readily available in
      convenience or nontraditional food stores. Among convenience and nontraditional
      food stores, "dollar" stores offered the best variety of more healthful canned
      fruits and vegetables, whole-wheat bread, and whole-grain cereal. Mass
      merchandisers and dollar stores offered a greater variety of more healthful types
      of canned tuna and poultry, reduced-fat and skim milk, and low-fat tortillas. In
      these rural counties, traditional food stores offered greater availability of
      more healthful food choices across food groups. More healthful food choices in
      canned fruits and vegetables, canned meat and fish, milk, and grains were also
      available in dollar stores, mass merchandisers, and convenience stores. Results
      suggest that a complete understanding of the food environment, especially in
      rural areas, requires knowledge of the availability and variety of healthful food
      in all types of stores that are accessible to families.

PMID- 19394476
TI  - "Restrained eating" vs "trying to lose weight": how are they associated with body
      weight and tendency to overeat among postmenopausal women?
AB  - In an effort to control body weight, many women diet or adopt a restrained
      approach to eating. Although common, dieting and dietary restraint remain poorly
      understood. Clarification of their association with health-related factors, such
      as body weight and overeating, is required. In this study, we explored how
      dieting and dietary restraint were associated with body mass index (BMI;
      calculated as kg/m2) and disinhibition (tendency to overeat) in a sample of 1,071
      postmenopausal women aged 45 to 75 years. In a survey of dietary attitudes and
      body image, we asked about current dieting status and measured restrained eating
      and disinhibition. Self-reported height and weight were used to calculate BMI,
      which was confirmed in a subset. Participants were classified by dieting status
      (yes/no) and level of dietary restraint (high/low by median split).We examined
      the independent effects of dieting and restrained eating on BMI and
      disinhibition. More than half of the sample (53%) reported current dieting.
      Dieting and dietary restraint showed opposite associations with BMI. Among
      dieters, BMI was 4.1 higher (95% confidence interval: 3.6 to 4.6) than among
      nondieters. In contrast, BMI of restrained eaters was 1.0 lower (95% confidence
      interval: -1.6 to -0.5) than unrestrained eaters. Dieters had higher scores for
      disinhibition, but disinhibition scores of restrained eaters did not differ from
      those of unrestrained eaters. Our results suggest that dieting and dietary
      restraint are not equivalent. Finding that dietary restraint is associated with
      lower BMI (when considered independently of dieting) suggests that restrained
      eating, rather than dieting, may contribute to successful weight management.

PMID- 19394474
TI  - Impact of dairy and sweetened beverage consumption on diet and weight of a
      multiethnic population of head start mothers.
AB  - Mothers with children in Head Start play a critical role in providing healthful
      diets and modeling good dietary behaviors to their children, but there is little
      information available on their diet, especially on beverage consumption. The
      objective of this study was to assess the association of milk and sweetened
      beverage consumption with nutrient intake, dietary adequacy, and weight of a
      multiethnic population of Head Start mothers. Using a cross-sectional, secondary
      analysis, African-American (43%), Hispanic (33%), and white (24%) women (n=609)
      were divided into four beverage consumption groups: high milk/low sweetened
      beverage, high milk/high sweetened beverage, low milk/low sweetened beverage, and
      low milk/high sweetened beverage. Nutrient intake was determined by averaging 24
      hour dietary recalls from 3 nonconsecutive days. Dietary adequacy was determined
      with the Mean Adequacy Ratio. Mean body mass index for the four beverage
      consumption groups was compared; there were no differences among the groups
      (overall mean+/-standard error=30.8+/-0.3). Women in the high milk/low sweetened
      beverage group had higher mean intakes of vitamins A, D, and B-6; riboflavin;
      thiamin; folate; phosphorus; calcium; iron; magnesium; and potassium (P<0.0125
      for all) when compared with the other beverage consumption groups. Mean Adequacy
      Ratio was highest in the high milk/low sweetened beverage (71.8+/-0.8) and lowest
      in the low milk/high sweetened beverage (58.4+/-0.8) consumption groups
      (P<0.0125). Women in the high milk/low sweetened beverage group consumed more
      nutrient-dense foods. Overall consumption of milk was low. Consumption of high
      milk/low sweetened beverage was associated with improved nutrient intake,
      including the shortfall nutrients, ie, calcium, potassium, magnesium, and vitamin
      A.

PMID- 19394477
TI  - Maternal education is associated with feeding style.
AB  - Maternal feeding styles may be influenced by maternal education, with
      implications for children's dietary quality and adiposity. One-hundred and eighty
      mothers completed the Parental Feeding Style Questionnaire, which includes scales
      assessing four aspects of feeding style, ie, control over feeding, emotional
      feeding, instrumental feeding, and encouragement/prompting to eat. Mothers with
      higher education had significantly higher scores on control over feeding
      [F(1,177)=8.79; P=0.003] and significantly lower emotional feeding scores
      [F(1,177)=7.26; P=0.008] than those with lower education. There were no
      differences for instrumental feeding or encouragement/prompting to eat (P>0.05).
      These findings suggest modest but potentially important differences in maternal
      control and emotional feeding styles by maternal education. Should these feeding
      characteristics prove salient to childhood diet and weight, this could inform
      appropriately targeted parental feeding advice.

PMID- 19394478
TI  - Comparison between dietary assessment methods for determining associations
      between nutrient intakes and bone mineral density in postmenopausal women.
AB  - It is important to identify the role of nutrition in the treatment and prevention
      of osteoporosis. The goal of this study was to compare the equivalency of
      nutrient intakes assessed by diet records and the Arizona Food Frequency
      Questionnaire and the associations of these nutrients with bone mineral density
      (BMD). This is a secondary analysis of cross-sectional data that was analyzed
      from six cohorts (fall 1995 to fall 1997) of postmenopausal women (n=244; 55.7+/
      4.6 years) participating in a 12-month, block-randomized, clinical trial. One
      year dietary intakes were assessed using 8 days of diet records and the Arizona
      Food Frequency Questionnaire. Participants' BMD was measured at the lumbar spine
      (L2-L4), femur trochanter, femur neck, Ward's triangle, and total body using dual
      energy x-ray absorptiometry. Linear regression analyses (P< or =0.05) were
      adjusted for the effects of exercise, hormone therapy use, body weight at 1 year,
      years post menopause, and total energy intake. Significant correlations (r=0.30
      to 0.70, P< or =0.05) between dietary assessment methods were found with all
      dietary intake variables. Iron and magnesium were consistently and significantly
      positively associated with BMD at all bone sites regardless of the dietary
      assessment method. Zinc, dietary calcium, phosphorous, potassium, total calcium,
      and fiber intakes were positively associated with BMD at three or more of the
      same bone sites regardless of the dietary assessment method. Protein, alcohol,
      caffeine, sodium, and vitamin E did not have any similar BMD associations. Diet
      records and the Arizona Food Frequency Questionnaire are acceptable dietary tools
      used to determine the associations of particular nutrients and BMD sites in
      healthy postmenopausal women.

PMID- 19394479
TI  - A comparison of two systems for entering and assessing dietary data for a
      research study.
AB  - To reduce the cost of analyzing dietary data for research studies, we evaluated
      the accuracy of an entry and assessment system that could be used by trained food
      and nutrition professionals who did not routinely perform this type of task. We
      compared intakes from 24-hour recalls for 175 adult women and 185 schoolchildren
      using two methods for entry of dietary data. For the standard method, registered
      dietitians who routinely evaluate dietary data entered the recalls using a
      professional data entry program, RapidCalc. For the second method, other food and
      nutrition professionals were trained by the registered dietitians to use the
      Pacific Tracker program, a consumer-friendly dietary assessment system. Both
      programs use the same food composition table. Mean food group and nutrient
      intakes were similar for the two methods, differing by <10% on average for both
      adults and children. Correlations were also high, ranging from 0.77 to 0.96 for
      the women and from 0.76 to 0.94 for the children. For adults and children
      combined, mean energy intakes were remarkably close, at 2,067 kcal/d for
      RapidCalc and 2,072 kcal/d for Pacific Tracker, although absolute differences in
      energy intakes were >300 kcal/d for 23% of the women and 30% of the children.
      Costs are much lower with the Pacific Tracker method, unless the fees for the
      standard method are subsidized. We conclude that the Pacific Tracker method
      provides an accurate and cost-effective method of dietary data entry for research
      purposes.

PMID- 19394480
TI  - Consumption of dry beans, peas, and lentils could improve diet quality in the US
      population.
AB  - The US Department of Agriculture's MyPyramid guidelines introduced a near
      doubling of the dietary recommendations for vegetables. These recommendations
      target specific subgroups of vegetables, including dry beans and peas. Dry beans
      and peas provide an array of nutrients and phytochemicals that have been shown to
      have beneficial health effects, yet consumption levels in the United States are
      quite low. Few studies have examined the influence of legume consumption on
      nutrient intakes. Therefore, the purpose of this study was to assess nutrient and
      food group intakes of dry bean and pea consumers compared to nonconsumers.
      Dietary intake data from the 1999-2002 National Health and Nutrition Examination
      Survey for adults aged > or =19 years was used. Results show that on any given
      day only 7.9% of adults are consuming dry beans and peas; Mexican Americans or
      other Hispanics are more likely to be consumers than nonconsumers. Consuming
      approximately (1/2) c dry beans or peas resulted in higher intakes of fiber,
      protein, folate, zinc, iron, and magnesium with lower intakes of saturated fat
      and total fat. These data support the specific recommendation for dry beans and
      peas as part of the overall vegetable recommendation. Increased consumption of
      dry beans and peas-economical and nutrient-rich foods-could improve the diet
      quality of Americans.

PMID- 19394481
TI  - A healthful options food station can improve satisfaction and generate gross
      profit in a worksite cafeteria.
AB  - The objectives of this study were to determine customer satisfaction with a
      healthful options food station offered in a worksite cafeteria and document the
      financial contribution of such a station. The healthful options station featured
      daily entrees with fewer than 500 calories and less than 30% of calories from
      fat. Questionnaires from 655 (24.5% response) employees and students provided
      data on satisfaction with and usage of the station. The majority of the
      respondents who had purchased from the healthful options station were female
      (77.3%), white (51.6%), aged 30 to 50 years (52.0%), and had annual incomes of
      $60,000 to $100,000 (29.3%) or $20,000 to $39,999 (22.2%). Sales and gross profit
      from the healthful options station were compared to those of the comfort station.
      Customers were satisfied with attributes of the healthful options station (means
      >3 on a 5-point scale). Results of paired t tests suggested that customers who
      had purchased from the healthful options station rated the station significantly
      (P<0.001) higher for healthfulness of entrees, food presentation, food quality,
      overall quality of the cafeteria, length of line, and food choices available
      compared to their ratings for the cafeteria in general. The healthful options
      station generated average daily sales of $458 and gross profit of $306. However,
      the sales and gross profit were significantly (P<0.05) less than the comparison
      comfort station.

PMID- 19394482
TI  - Vitamin D: are children and adolescents at risk for deficiency?

PMID- 19394483
TI  - SIU scholarship: Dr. Blessing Ngonidzashe Dziwa.

PMID- 19394484
TI  - SIU scholarship: Dr. Pius Mutune Musau.

PMID- 19394485
TI  - Editorial comment.

PMID- 19394487
TI  - Peter Lester Scardino--a genitourinary surgeon in third generation of the
      specialty: part 1.

PMID- 19394488
TI  - Peter Lester Scardino--a genitourinary surgeon in third generation of the
      specialty: part 2.

PMID- 19394489
TI  - Investigation of human anti-mouse antibodies as potential cause of
      postprostatectomy PSA elevation.

PMID- 19394491
TI  - Semirigid ureteroscopy and pneumatic lithotripsy as definitive management of
      obstructive ureteral calculi during pregnancy.
AB  - OBJECTIVES: To assess the results of semirigid ureteroscopy and intracorporeal
      pneumatic lithotripsy as a definitive treatment option for women presenting with
      obstructive ureteral calculi during pregnancy. METHODS: A retrospective analysis
      was performed of 19 pregnant patients referred to our tertiary care center with
      ureteral obstruction necessitating surgical intervention from 1997 to 2007. The
      mean patient age was 22 years (range 18-27), and the mean gestation period was 20
      weeks (range 14-34). Of the 19 patients, 21% were febrile, 32% had positive urine
      cultures, and 63% had pyuria and microscopic hematuria. Abdominal ultrasonography
      was the principle diagnostic test used. Six patients had history of renal stones
      before conception. The mean stone size was 11 mm, (range 8-18). Of the 19
      patients, 58% had stones located in the proximal and 42% in the distal ureter.
      The stones were fragmented using a Swiss pneumatic lithoclast through a 6.9F/8F
      semirigid ureteroscope with the patient under general anesthesia. None of the
      patients underwent limited intravenous urography or computed tomography except
      for 1, who underwent plain x-ray of the kidneys, ureters, and bladder. RESULTS:
      All patients had obstruction due to the ureteral calculi, and 79% patients had
      complete fragmentation of the calculi by ureteroscopy as the primary treatment.
      Of the 19 patients, 63% required ureteral stent insertion per operatively. No
      complications related to the procedure itself or the general anesthesia were
      recorded, and all patients completed the full term of pregnancy. CONCLUSIONS: The
      results of our study have shown that semirigid ureteroscopy to diagnose ureteral
      calculi and treat them with intracorporeal pneumatic lithotripsy and ureteral
      stent insertion, as indicated, is the most efficient and definitive treatment
      modality in expectant women.

PMID- 19394490
TI  - Association of C-reactive protein and lower urinary tract symptoms in men and
      women: results from Boston Area Community Health survey.
AB  - OBJECTIVES: To determine whether an association exists between C-reactive protein
      (CRP) levels and lower urinary tract symptoms (LUTS) as assessed by the American
      Urological Association Symptom Index (AUA-SI) among both men and women, and to
      determine the association of CRP levels with the individual urologic symptoms
      comprising the AUA-SI among both men and women. METHODS: The Boston Area
      Community Health survey used a multistage stratified design to recruit a random
      sample of 5502 adults aged 30-79 years. Blood samples were obtained from 3752
      participants. The analyses were conducted on 1898 men and 1854 women with
      complete data on CRP levels. Overall LUTS was defined as an AUA-SI of >or=8
      (moderate to severe LUTS). The urologic symptoms comprising the AUA-SI were
      included in the analysis as reports of fairly often to almost always vs
      non/rarely/a few times. RESULTS: A statistically significant association was
      observed between the CRP levels and overall LUTS among both men and women. The
      pattern of associations between the individual symptoms and CRP levels varied by
      sex. Nocturia and straining were associated with greater CRP levels among men,
      and incomplete emptying and weak stream were associated with greater CRP levels
      among women. CONCLUSIONS: The results of this study have demonstrated an
      association between CRP levels and LUTS in both men and women. The dose-response
      relationship between increased CRP levels and an increased odds of LUTS supports
      the hypothesized role of inflammatory processes in the etiology of LUTS.

PMID- 19394492
TI  - Relationships between carbonation rate of carbapatite and morphologic
      characteristics of calcium phosphate stones and etiology.
AB  - OBJECTIVES: To examine the significance of the carbonation rate (CR) in
      carbonated apatite (carbapatite [CA]) stones and its relationships with the
      morphologic characteristics of CA and etiology. CA stones without struvite can
      result from metabolic disorders or urinary tract infection, but the latter
      etiology is still debated. Infection stones caused by urea-splitting bacteria are
      made of CA admixed with struvite and exhibit a high CO(3)(2-)/PO(4)(3-) ratio
      (CR). However, little is known as to the significance of the CR of CA in the
      absence of struvite in idiopathic calcium phosphate stones. METHODS: We studied
      39 urinary calculi mainly composed of CA without struvite. Of the 39 patients, 13
      had a past or present history of urinary tract infection, 24 had hypercalciuria,
      and 2 had medullary sponge kidney. The stones were examined by Fourier transform
      infrared spectroscopy and scanning electron microscopy. The presence of amorphous
      carbonated calcium phosphate or whitlockite was also considered. RESULTS: The CR
      of CA was 14% +/- 9%. On scanning electron microscopy, the CA particles appeared
      as spherules of 4.5 +/- 3.0 mum in diameter and were significantly larger in
      females than in males. In 16 cases, scanning electron microscopy showed bacterial
      imprints. In these calculi, the CR was significantly greater (22% +/- 7%) than in
      those without a visible bacterial imprint (8% +/- 5%, P < .0001). Amorphous
      carbonated calcium phosphate was found in 15 of 16 stones (93.8%) with imprints
      and in none of the 23 stones without imprints (P < .0001). CONCLUSIONS: A close
      relationship was observed between the presence of bacterial imprints, indicative
      of past or current urinary tract infection, and both the presence of amorphous
      carbonated calcium phosphate (or whitlockite) and a high CR of CA.

PMID- 19394493
TI  - Systematic evaluation of ureteral occlusion devices: insertion, deployment, stone
      migration, and extraction.
AB  - OBJECTIVES: To compare 4 ureteral occlusion devices in terms of insertion force,
      maneuverability, radial dilation and extraction forces, ability to prevent stone
      migration, and tip stiffness. METHODS: The devices tested were the PercSys
      Accordion, Microvasive Stone Cone (7 and 10 mm), and Cook N-Trap. Using a
      ureteral model with an artificial stone in place, the insertion force, number of
      attempts, and time to pass the impacted stone were measured. Using a Teflon block
      model, radial dilation and extraction and axial extraction force were measured
      with a load cell. Holmium lithotripsy was performed in the ureteral model with a
      canine stone in place to test the ability of the devices to prevent stone
      migration. In a similar model, the force applied to retrieve the canine stone was
      measured. The stiffness of the tip was measured as the force to compress a 5-mm
      length of the tip in a clamp-clamp configuration on a linear motion stage driven
      by a stepper motor with a resolution of 8-mum/step. RESULTS: The devices were
      significantly different statistically from each other in terms of insertion
      force, number of attempts and time to pass the impacted stone, radial dilation,
      radial extraction, and axial extraction force in the Teflon block model. No
      proximal migration of the stones occurred with any of the devices. The devices
      were similar in terms of preventing proximal stone migration, force applied to
      retrieve stones, and tip stiffness. CONCLUSIONS: The differences in the physical
      characteristics of stone migration devices might help to predict their safety and
      efficacy in clinical use.

PMID- 19394494
TI  - Sexual functioning, catastrophizing, depression, and pain, as predictors of
      quality of life in women with interstitial cystitis/painful bladder syndrome.
AB  - OBJECTIVES: To study the association of sexual dysfunction with quality of life
      (QOL) while simultaneously examining the shared influence of empirically
      supported variables that are also associated with diminished interstitial
      cystitis/painful bladder syndrome (IC/PBS) QOL (ie, pain, catastrophizing,
      depression). Previous research has indicated that sexual dysfunction is
      prevalent, bothersome, and an important predictor of diminished QOL in patients
      with IC/PBS. However, the deleterious association between sexual dysfunction and
      QOL has not been investigated in more inclusive models that use validated
      measures. METHODS: Women were recruited from 3 North American centers who agreed
      to the study and completed measures of QOL, pain severity, IC/PBS symptoms and
      bother (IC Symptom Index, IC Problem Index), pain catastrophizing, depression,
      and sexual dysfunction. Hierarchical multivariate regression was executed to test
      both unique and combined effects. RESULTS: A total of 115 women, with a mean age
      of 50 years, participated in this study. Regression modeling showed that
      diminished QOL physical composite scores were predicted by a longer symptom
      duration (P = .013), unemployment (P = .017), and greater pain severity (P =
      .004). In regard to the diminished QOL mental composite scores, the lone
      predictors included age (P = .029) and pain catastrophizing (P = .002).
      CONCLUSIONS: In disagreement with previous research, sexual functioning was not
      associated with diminished physical or mental composites of patient QOL.
      Furthermore, these data suggest that demographic factors and pain might be
      predictive of poorer QOL outcomes, and that anxious worry about pain (ie,
      catastrophizing) is a target for future research and clinical intervention.

PMID- 19394495
TI  - Neovesical-urethral anastomotic stricture due to external suture migration.
AB  - We report on the endoscopic appearance and subsequent treatment of a neovesical
      urethral anastomotic stricture caused by migration of a nonabsorbable suture
      originally placed for retropubic hemostasis.

PMID- 19394497
TI  - Editorial comment.

PMID- 19394498
TI  - Role of urinary tubular enzymes in evaluation of children with ureteropelvic
      junction narrowing under conservative management.
AB  - OBJECTIVES: To evaluate the role of urinary lysosomal enzyme N-acetyl-beta-D
      glucosaminidase (NAG) and brush border enzymes alkaline phosphatase (ALP) and
      gamma-glutamyl transferase (GGT) in the long-term follow-up of children under
      conservative management for ureteropelvic junction narrowing. METHODS: The study
      included 30 children with dilated nonobstructed kidneys due to unilateral
      ureteropelvic junction narrowing who were treated conservatively and followed up
      for 15 months. Voided urine samples were obtained from the children at diagnosis
      and at 3, 9, and 15 months of follow-up. NAG, ALP, and GGT were measured in these
      urine samples. RESULTS: The conservative management of the children during their
      follow-up period revealed stabilization of renal function in 15 patients (dilated
      nonobstructed group) and deterioration in 15 (obstructed group). In patients
      considered to have dilated nonobstructed kidneys, a comparison between the mean
      values of urinary NAG, ALP, and GGT at the last follow-up and at baseline showed
      no significant differences. In addition, the mean values of glomerular filtration
      rate and split renal function showed no significant changes at the last follow-up
      examination compared with the basal condition. In patients considered to have
      obstructed kidneys, a comparison between the mean values of the 3 enzymes at
      diagnosis and at basal condition showed a significant increase in the 3 urinary
      biomarkers. Moreover, the mean values of the glomerular filtration rate and split
      renal function showed a significant reduction at diagnosis compared with the
      basal condition. CONCLUSIONS: NAG, ALP, and GGT are noninvasive biomarkers that
      could be used for long-term follow-up of children with ureteropelvic junction
      narrowing under conservative management to determine those who might develop
      obstruction.

PMID- 19394499
TI  - Electroacupuncture relieves pain in men with chronic prostatitis/chronic pelvic
      pain syndrome: three-arm randomized trial.
AB  - OBJECTIVES: To investigate the clinical effect of electroacupuncture (EA) for
      chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We recruited
      63 participants meeting the U.S. National Institutes of Health (NIH) consensus
      criteria for CP/CPPS. After the inclusion/exclusion criteria were applied, 39 men
      were randomized to 3 treatment groups: group 1, advice and exercise plus 12
      sessions of EA; group 2, advice and exercise plus 12 sessions of sham EA (SEA);
      and group 3, advice and exercise alone (A&E) for 6 weeks. A total of 6
      acupuncture points were used to stimulate the sacral nerve and release the
      piriformis muscle using an electrical pulse generator. Symptoms related to
      CP/CPPS were assessed using the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI).
      Prostaglandin E(2) and beta-endorphin levels in postmassage urine samples were
      measured using an enzyme-linked immunosorbent assay. RESULTS: At 6 weeks, the NIH
      CPSI total score had decreased significantly in the EA group compared with the
      SEA and A&E groups (P < .001). On a subscale analysis of the NIH-CPSI, the EA
      group showed significant decreases in pain-related symptoms compared with the SEA
      and A&E groups (P < .01). All 12 EA participants experienced at least a 6-point
      decrease in the NIH-CPSI total score compared with 2 of 12 SEA participants
      (16.7%) and 3 of 12 A&E participants (25.0%; P < .0001). The mean prostaglandin
      E(2) level in the postmassage urine samples had significantly decreased in the EA
      group (P = .023). In contrast, it had increased in the other 2 groups.
      CONCLUSIONS: In a 3-arm randomized trial investigating the clinical effects of EA
      on CP/CPPS, EA therapy proved to have independent therapeutic effects,
      particularly for pain relief superior to SEA or A&E therapy.

PMID- 19394500
TI  - Holmium laser enucleation of prostate: outcome and complications of self-taught
      learning curve.
AB  - OBJECTIVES: To analyze the self-learning curve of a single surgeon with holmium
      laser enucleation of the prostate and to evaluate the safety, effectiveness, and
      outcome of the procedure after 2 years of experience. METHODS: The data from the
      first 125 patients who underwent holmium laser enucleation of the prostate were
      retrospectively analyzed. The patients were assessed preoperatively and at 1, 3,
      12, and 24 months postoperatively. The patient evaluations included serum
      prostate-specific antigen measurement, peak urinary flow rate determination,
      postvoid residual volume measurement, and symptom scores. To assess the effect of
      the learning curve on the perioperative data and complications, the patients were
      divided into subgroups of 25 consecutive patients. RESULTS: The mean patient age
      was 71.4 years. The average prostate volume was 75.8 mL, and the mean weight of
      the enucleated tissue was 46.7 g. The average operative time was 109.8 minutes.
      The operative times and enucleation and morcellation efficiency rates improved
      significantly during the learning process. The mean hemoglobin loss was 1.7 g/dL.
      The median catheter time and hospital stay was 44 and 30 hours, respectively.
      Compared with baseline, at 1 year postoperatively, the median postvoid residual
      urine volume had declined by 99 mL, the mean peak urinary flow rate had increased
      by 19 mL/s, and the mean American Urological Association symptom score had
      decreased by 16.5 points. All changes observed were significant and regardless of
      the prostate size. Persistent stress urinary incontinence (4.8%) occurred with
      the first enucleations of large-size prostates. Other complications included
      bladder neck contracture (4%) in small-size prostates and bulbar urethra
      stricture (1.6%). CONCLUSIONS: Holmium laser enucleation of the prostate is a
      safe, reproducible and effective surgical modality. Case selection is necessary
      to avoid the morbidity associated with the first stages of the self-taught
      learning curve, mainly urinary incontinence.

PMID- 19394501
TI  - Editorial comment.

PMID- 19394504
TI  - Laparoscopic adrenalectomy for beginners without open counterpart experience:
      initial results under staged training.
AB  - OBJECTIVES: To develop a staged laparoscopic training program for beginners to
      perform laparoscopic adrenalectomy (LA) and to determine its safety and
      feasibility. METHODS: From January 2002 to October 2007, 5 beginners
      (postgraduate years 1-5) without previous experience in open adrenalectomy were
      selected randomly to receive the staged laparoscopic training, including box
      trainer, animal model, and mentor-initiated clinical training. During the
      clinical training, the trainees acted as the camera holder first, and then
      selectively performed simple operations, such as laparoscopic renal cyst
      unroofing. Finally, they performed 30 LAs independently under the mentor's
      supervision using the technique of anatomic retroperitoneoscopic adrenalectomy.
      The clinical data of the 30 LAs performed by each the trainees (150 LAs total)
      were collected and compared with the data from the initial 30 LAs of the mentor.
      RESULTS: All LAs were completed successfully. No procedure required conversion to
      open surgery. The median operative time of the trainees was 82.3 minutes (range
      59-133), which was obviously shorten than the mentor's (median operative time
      131.5 minutes, range 73-230, P < .001). The learning curve among the trainees was
      shorter compared with that of the mentor. No major complications were observed.
      The minor intraoperative and postoperative complication rate for the trainees was
      0.67% and 6.7%, respectively, not significantly different from those of the
      mentor (0% and 3.3%, respectively; both P > .05). All complications developing in
      patients treated by the trainees required only conservative therapy. CONCLUSIONS:
      It was safe and feasible for beginners without previous open counterpart
      experience to perform LA using staged training.

PMID- 19394503
TI  - Effect of nicardipine on renal function after robot-assisted laparoscopic radical
      prostatectomy.
AB  - OBJECTIVES: To investigate the renoprotective effect of nicardipine in patients
      undergoing robot-assisted laparoscopic radical prostatectomy (RALRP) in a
      prospective trial. Superior visualization of the increasingly performed RALRP
      requires pneumoperitoneum and extreme head-down tilt, both of which are
      associated with a decrease in postoperative renal function. Nicardipine causes
      preferential dilation of the renal arterioles and attenuates renal dysfunction
      after cardiac surgery. METHODS: After we obtained institutional review board
      approval, we randomly treated 100 patients undergoing RALRP with a continuous
      infusion of nicardipine at a rate of 0.5 microg/kg/min (nicardipine group, n =
      50) or with normal saline (control group, n = 50) during surgery. We measured the
      serum creatinine (Cr) level and estimated glomerular filtration rate (eGFR) 1 day
      before surgery and the first and third postoperative days (POD 1 and 3,
      respectively). RESULTS: Patients' characteristics and operative data were similar
      between groups. The serum Cr was significantly higher and the eGFR was
      significantly lower in the control group at POD 1. The number of patients having
      renal insufficiency (eGFR < 60 mL/min/1.73 m(2)) and abnormal serum creatinine
      level (>1.4 mg/dL) was significantly greater in the control group (9 vs 1, and 4
      vs none, respectively) at POD 1. CONCLUSIONS: Continuous infusion of low-dose
      nicardipine during RALRP seems to offset the deleterious effects of inevitable
      pneumoperitoneum and extreme head-down tilt on renal function in preserving the
      eGFR and attenuating the development of renal insufficiency in the immediate
      postoperative period.

PMID- 19394505
TI  - Editorial comment.

PMID- 19394507
TI  - Current perceptions of resident training in laparoscopic nephrectomy.
AB  - OBJECTIVES: To determine the perceived degree of training of residents in
      laparoscopic nephrectomy. Laparoscopic nephrectomy is well established in the
      field of urology and has seen increasing penetrance in urologic practice. The
      degree to which this recent technical shift has been integrated into urologic
      training at the residency level has not been characterized. METHODS: An
      electronic survey was sent to 518 urology residents and recent graduates and to
      85 laparoscopic specialists at academic medical centers. Both residents and
      practicing urologists were queried regarding the level of resident participation
      for each step of laparoscopic nephrectomy and opinions on the necessity of
      fellowship training. The data were analyzed using the Wilcoxon rank-sum and
      chi(2) tests. RESULTS: Attending surgeons perceived a significantly greater level
      of resident involvement in performing all aspects of laparoscopic nephrectomy,
      with the exception of hilar dissection and port closure. To perform laparoscopic
      nephrectomy, 12.5% of attending physicians and 5% of residents reported that a
      fellowship is necessary. CONCLUSIONS: Significant disagreement exists between
      attending surgeons and residents on the perceived degree of resident involvement
      in most aspects of laparoscopic nephrectomy. This could have significant
      implications on resident education for a procedure that is arguably the standard
      of care for treatment of uncomplicated renal masses. Most attending physicians
      and residents were in agreement that fellowship is not necessary to perform this
      procedure. These results raise questions regarding the future of laparoscopic
      training and bring to light the need for better regulation of laparoscopic
      training.

PMID- 19394508
TI  - Editorial comment.

PMID- 19394509
TI  - Laparoscopic radical versus partial nephrectomy for tumors >4 cm: intermediate
      term oncologic and functional outcomes.
AB  - OBJECTIVES: To compare the oncologic and functional outcomes of laparoscopic
      radical nephrectomy (LRN) and laparoscopic partial nephrectomy (LPN) for clinical
      Stage T1b-T3 renal cell carcinoma >4 cm in size. METHODS: This retrospective
      analysis compared patients undergoing LRN (n = 75) or LPN (n = 35) at a tertiary
      referral center from April 2001 to December 2005 for Stage T1b-T3N0M0 renal cell
      carcinoma. The endpoints included radiologically verified systemic and local
      recurrence, cancer-specific mortality, overall mortality, and chronic kidney
      disease as determined from the calculated glomerular filtration rate and Kidney
      Foundation Dialysis Outcomes Quality Initiative diagnostic criteria. RESULTS: The
      LRN group had larger tumors (5.3 vs 4.9 cm; P = .03), more T3a tumors (33% vs 9%;
      P = .006), and more clear cell pathologic features (85% vs 66%; P = .03). No
      surgical margins in either group were positive. The median follow-up was 57
      months (range 27-79) for the LRN group and 44 months (range 27-85) for the LPN
      group (P = .1). The overall mortality (11% vs 11%), cancer-specific mortality (3%
      vs 3%), and recurrence (3% vs 6%) rates (P = .4) were equivalent. The
      postoperative decrease in the estimated glomerular filtration rate was less in
      the LPN group than in the LRN group at 13 and 24 mL/min, respectively (P = .03).
      Postoperatively, 2-stage increases in the chronic kidney disease stage occurred
      in 12% vs 0% of patients in the LRN and LPN groups, respectively (P < .001).
      CONCLUSIONS: Our intermediate-term data have indicated that in appropriate
      patients with Stage T1b-T3 tumors >4 cm, LPN provides equivalent oncologic
      efficacy and superior renal functional outcomes compared with LRN. Future studies
      are required to confirm these trends.

PMID- 19394510
TI  - Editorial comment.

PMID- 19394512
TI  - Posterior sagittal pararectal approach with rectal mobilization for repair of
      rectourethral fistula: an alternative approach.
AB  - OBJECTIVES: To present this clinical series to report our initial experience with
      our technique as an alternative approach for treatment of rectourethral fistulas
      (RUFs). RUFS are a devastating complication of the urinary tract. The most
      appropriate approach remains controversial. METHODS: From March 2002 to August
      2007, 8 patients with RUF were referred to our institution. The etiology of the
      RUF was a fractured pelvis in 2, radical prostatectomy in 1, transurethral
      resection of the prostate in 1, anterior bowel resection in 1, and a pull-through
      operation in 3. Of the 8 patients, 5 had undergone urinary diversion and 3 had
      undergone a previous repair that had failed. They were evaluated and treated
      using the posterior sagittal approach with rectal mobilization. The fistulas were
      excised, and both the urethra and rectum were repaired. The inferior half of the
      gluteus maximus muscle was used as barrier in 5 of the 8 patients. The operative
      and immediate and late postoperative complications were recorded. The clinical
      outcome was defined as success when the patients experienced no fecaluria or
      pneumaturia. RESULTS: All 8 patients, with a mean age of 38.7 years, were
      completely cured of their RUF. The mean operative time was 290 minutes, and the
      mean blood loss was 637.5 mL. The median hospital stay was 18 days. Early
      postoperative complications included wound infection in 1 and deep vein
      thrombosis in 1 patient. One patient developed a late complication of urinary
      incontinence. CONCLUSIONS: Our approach is safe, provides excellent exposure, and
      allows for dissection under direct vision. The gluteus maximus flap is a good,
      nearby flap that can be used with minimal host morbidity.

PMID- 19394511
TI  - Prevalence of skeletal complications and their impact on survival of hormone
      refractory prostate cancer patients in Japan.
AB  - OBJECTIVES: Skeletal complications are a crucial factor in the quality of life
      and the prognosis of patients with hormone-refractory prostate cancer (HRPC);
      however, their true prevalence and impact on the prognosis remain largely
      unknown. In this study, we retrospectively investigated the prevalence of
      skeletal complications and survival of HRPC patients in a single Japanese
      institute. METHODS: From 1990 to 2004, 151 patients with prostate cancer were
      estimated to have HRPC after androgen ablation therapy in a single institute. The
      medical records of the patients were reviewed for documentation of skeletal
      complications, and overall survival was calculated from the diagnosis of HRPC.
      RESULTS: At the diagnosis of HRPC, bone metastases and bone pain were observed in
      83.8% and 44.7% of patients, respectively. During follow-up, 80.0% and 14.2% of
      patients experienced bone pain and bone fracture, respectively. Moreover, 74.2%
      and 43.9% of the patients received nonsteroidal anti-inflammatory drugs and
      opioids for bone pain, respectively, and 50.9% of the patients underwent
      radiotherapy for palliative pain control. A high score on the extent of disease
      observed on the bone scan and the presence of bone pain at the diagnosis of HRPC
      were independent prognostic factors on multivariate analysis (hazard ratio =
      1.753 and 2.118, P = .033 and .007, respectively). CONCLUSIONS: Despite a small
      number of subjects, our retrospective survey demonstrated the high prevalence and
      mortality rate of skeletal complications in Japanese HRPC patients. Patients with
      bone pain at the diagnosis of HRPC had significantly poorer prognosis than those
      without.

PMID- 19394513
TI  - Editorial comment.

PMID- 19394515
TI  - Medical emergency in Sri Lanka.

PMID- 19394516
TI  - How ethical are for-profit institutional review boards?

PMID- 19394517
TI  - Resistance to the Affordable Medicines Facility for malaria?

PMID- 19394518
TI  - Emergence of clinical vascular tissue engineering.

PMID- 19394519
TI  - Ideas and ideals: ethical basis of health reform in Mexico.

PMID- 19394520
TI  - Malaria: 2 years in the fast lane.

PMID- 19394521
TI  - A vaccine against malaria: a substantial step forward.

PMID- 19394522
TI  - Bob Snow: championing malaria in Africa.

PMID- 19394523
TI  - Glycaemic control in paediatric critical care.

PMID- 19394524
TI  - Glycaemic control in paediatric critical care.

PMID- 19394525
TI  - Glycaemic control in paediatric critical care.

PMID- 19394526
TI  - Ethical criteria for allocating health-care resources.

PMID- 19394529
TI  - Ethical criteria for allocating health-care resources.

PMID- 19394530
TI  - PTC124 for cystic fibrosis.

PMID- 19394532
TI  - Humanitarian crisis in Vanni, Sri Lanka.

PMID- 19394533
TI  - Assessment of childhood immunisation coverage.

PMID- 19394534
TI  - Assessment of childhood immunisation coverage.

PMID- 19394535
TI  - Effectiveness of haemodialysis access with an autologous tissue-engineered
      vascular graft: a multicentre cohort study.
AB  - BACKGROUND: Application of a tissue-engineered vascular graft for small-diameter
      vascular reconstruction has been a long awaited and much anticipated advance for
      vascular surgery. We report results after a minimum of 6 months of follow-up for
      the first ten patients implanted with a completely biological and autologous
      tissue-engineered vascular graft. METHODS: Ten patients with end-stage renal
      disease who had been receiving haemodialysis through an access graft that had a
      high probability of failure, and had had at least one previous access failure,
      were enrolled from centres in Argentina and Poland between September, 2004, and
      April, 2007. Completely autologous tissue-engineered vascular grafts were grown
      in culture supplemented with bovine serum, implanted as arteriovenous shunts, and
      assessed for both mechanical stability during the safety phase (0-3 months) and
      effectiveness after haemodialysis was started. FINDINGS: Three grafts failed
      within the safety phase, which is consistent with failure rates expected for this
      high-risk patient population. One patient was withdrawn from the study because of
      severe gastrointestinal bleeding shortly before implantation, and another died of
      unrelated causes during the safety period with a patent graft. The remaining five
      patients had grafts functioning for haemodialysis 6-20 months after implantation,
      and a total of 68 patient-months of patency. In these five patients, only one
      intervention (surgical correction) was needed to maintain secondary patency.
      Overall, primary patency was maintained in seven (78%) of the remaining nine
      patients 1 month after implantation and five (60%) of the remaining eight
      patients 6 months after implantation. INTERPRETATION: Our proportion of primary
      patency in this high-risk cohort approaches Dialysis Outcomes Quality Initiative
      objectives (76% of patients 3 months after implantation) for arteriovenous
      fistulas, averaged across all patient populations.

PMID- 19394536
TI  - Green urine.

PMID- 19394537
TI  - Early breast cancer.
AB  - Adoption of urbanised lifestyles together with changes in reproductive behaviour
      might partly underlie the continued rise in worldwide incidence of breast cancer.
      Widespread mammographic screening and effective systemic therapies have led to a
      stage shift at presentation and mortality reductions in the past two decades.
      Loco-regional control of the disease seems to affect long-term survival, and
      attention to surgical margins together with improved radiotherapy techniques
      could further contribute to mortality gains. Developments in oncoplastic surgery
      and partial-breast reconstruction have improved cosmetic outcomes after breast
      conservation surgery. Optimum approaches for delivering chest-wall radiotherapy
      in the context of immediate breast reconstruction present special challenges.
      Accurate methods for intraoperative assessment of sentinel lymph nodes remain a
      clinical priority. Clinical trials are investigating combinatorial therapies that
      use novel agents targeting growth factor receptors, signal transduction pathways,
      and tumour angiogenesis. Gene-expression profiling offers the potential to
      provide accurate prognostic and predictive information, with selection of best
      possible therapy for individuals and avoidance of overtreatment and
      undertreatment of patients with conventional chemotherapy. Short-term presurgical
      studies in the neoadjuvant setting allow monitoring of proliferative indices, and
      changes in gene-expression patterns can be predictive of response to therapies
      and long-term outcome.

PMID- 19394538
TI  - Coeliac disease.
AB  - Coeliac disease is a chronic inflammatory disorder of the small bowel induced in
      genetically susceptible people by the irritant gluten and possibly other
      environmental cofactors. The disorder is characterised by a diverse clinical
      heterogeneity that ranges from asymptomatic to severely symptomatic, and it
      manifests with frank malabsorption, an increased morbidity attributable to the
      frequent association with autoimmune disorders and increased mortality resulting
      from the emergence of T-cell clonal proliferations that predispose the patient to
      enteropathy-type T-cell lymphoma. Our understanding of the molecular basis for
      this disorder has improved and enabled the identification of targets for new
      therapies, although a strict gluten-free diet remains the mainstay of safe and
      effective treatment. In this Seminar we critically reassess the clinical and
      diagnostic aspects of this disease and new perspectives in its pathogenesis and
      treatment.

PMID- 19394539
TI  - Painless jaundice with serial multi-organ dysfunction.

PMID- 19394540
TI  - Prediction of 30-day mortality after endovascular repair or open surgery in
      patients with ruptured abdominal aortic aneurysms.
AB  - OBJECTIVE: To validate the Glasgow Aneurysm Score (GAS) in patients with ruptured
      abdominal aortic aneurysms (AAAs) treated with endovascular repair or open
      surgery and to update the GAS so that it predicts 30-day mortality for patients
      with ruptured AAA treated with endovascular repair or open surgery. METHODS: In a
      multicenter prospective observational study, 233 consecutive patients with
      ruptured AAAs were evaluated; 32 patients did not survive to repair and
      statistical analysis was performed using collected data on 201 patients. All
      patients who were treated with endovascular repair (n = 58) or open surgery (n =
      143) were included. The GAS was calculated for each patient. The area under the
      receiver operating characteristics curve (AUC) was used to indicate
      discriminative ability. We tested for interactions between risk factors and the
      procedure performed. The GAS was updated to predict 30-day mortality after
      endovascular repair or open surgery in patients with ruptured AAAs using logistic
      regression analysis. RESULTS: Thirty-day mortality was 15/58 (26%) for patients
      treated with endovascular repair and 57/143 (40%) for patients treated with open
      surgery (P = .06). The AUC for GAS was 0.69. No relevant interactions were found.
      The updated prediction rule (AUC = 0.70) can be calculated with the following
      formula: + 7 for open surgery + age in years + 17 for shock + 7 for myocardial
      disease + 10 for cerebrovascular disease + 14 for renal insufficiency.
      CONCLUSION: We showed limited discriminative ability of the GAS and therefore
      updated the GAS by adding the type of procedure performed. This updated
      prediction rule predicts 30-day mortality for patients with ruptured AAAs treated
      with endovascular repair or open surgery.

PMID- 19394541
TI  - A modern theory of paraplegia in the treatment of aneurysms of the
      thoracoabdominal aorta: An analysis of technique specific observed/expected
      ratios for paralysis.
AB  - OBJECTIVE: To demonstrate that a modern theory of paraplegia prevention in
      thoracoabdominal aortic (TAAA) surgery is primarily non-anatomic and derives from
      experimentally validated interventions that prolong the ischemic tolerance,
      reduce reperfusion injury, and enhance the collateral perfusion of the spinal
      cord with or without assisted circulation. METHODS: Using an accurate predictive
      model (r(2) > 0.95) for paraplegia risk we studied the effects of protective
      strategies in 82 clinical series reporting more than 15,000 patients treated from
      1985 to 2008. The observed/expected (O/E) ratios were calculated for each series
      and the results were grouped by technique. The effect of interventions such as
      spinal fluid drainage (SFD), systemic hypothermia, epidural cooling, and naloxone
      on O/E ratios were studied. We analyzed changes in O/E ratios from Era 1 (1985 to
      1997) to Era 2 (1997 to 2008) and within treatment techniques over time. RESULTS:
      The mean O/E ratio for paraplegia for all patients declined from 1.13 in Era 1 to
      0.26 in Era 2. Adding SFD to patients treated with assisted circulation (AC)
      decreased the O/E ratio from 1.03 to 0.24 (P < .0001). Adding SFD to patients
      treated with aortic clamping without AC (XCL) decreased O/E from 0.91 to 0.23 (P
      = .0013). O/E for hypothermic arrest (HA) declined from 0.42 to 0.14 with SFD.
      The addition of SFD to AC, XCL, and HA accounted for most of the decline in O/E
      between Eras. Other factors which played a less defined but important role in the
      decline in O/E ratios were attention to higher mean arterial pressures (MAPs),
      more hypothermia, and neurochemical protection. CONCLUSION: Paraplegia causation
      is anatomic but paraplegia prevention is physiologic (non-anatomic). We
      demonstrate that by using hypothermia, SFD, and increasing MAP, clinicians had
      similar improvements in paraplegia, reducing O/E deficit ratios from 1.03 to as
      low as 0.16, with or without intercostal reimplantation, and whether or not
      assisted circulation was used. Understanding the fundamental principles of
      paraplegia prevention and how to apply protective strategies leads to a reduction
      in paralysis in clinical series with or without the use of assisted circulation.
      This modern theory of paraplegia has significant implications for the rapidly
      advancing field of TAAA repair with branched endografts where the same principles
      apply.

PMID- 19394542
TI  - Combined endovascular and surgical approach (CESA) to thoracoabdominal aortic
      pathology: A 10-year experience.
AB  - OBJECTIVE: The first combined endovascular and surgical approach for
      thoracoabdominal aortic aneurysm was performed at our institution in 1998. We
      report a 10-year experience with a hybrid approach to thoracoabdominal aortic
      pathology. METHODS: Records of all patients undergoing a combined endovascular
      and surgical approach to thoracoabdominal aortic pathology were reviewed.
      Presenting symptoms, perioperative morbidity and mortality, sequence (single
      versus two stages), and late results were analyzed. RESULTS: From 1998 to 2008,
      20 patients were treated with hybrid repairs for thoracoabdominal aneurysm (TAA)
      (15; four with dissection), aortic arch aneurysm (two), symptomatic supravisceral
      abdominal aortic aneurysm (one), contained perirenal pseudoaneurysm rupture
      (one), and floating aortic arch thrombus with cerebral and renal emboli in one
      patient. Ten patients had prior aortic grafting, one patient had a functional
      renal transplant, and all patients were considered high risk based on
      preoperative comorbidities. Aneurysm related pain (11) or aneurysm growth
      (eight), mesenteric ischemic symptoms (four), and peripheral embolization (one)
      were indications for intervention. Spinal catheter drainage was used routinely.
      The procedure was completed in a single stage (13), or two stages using a
      subcutaneous conduit constructed at the first stage (six). One patient refused
      the second stage and expired from aneurysm rupture five months later. There were
      nine major complications in six patients (32% morbidity); all recovered except
      one patient with complete aortic coverage from left subclavian to bifurcation in
      the single stage group who developed paraplegia (one of 15 patients at risk;
      6.6%). There was no perioperative mortality (0-30 days or discharge). Two
      patients had successful re-intervention for a type I (included as a major
      complication) and II endoleak respectively. Two type II endoleaks without
      aneurysm growth continue under observation. There has been no graft thrombosis,
      aneurysm growth, or rupture during a mean follow-up of 16.6 months (range, 1-119
      months) in 19 patients with a completed procedure (none lost to follow up).
      Cumulative survival at two years is 76%. CONCLUSIONS: A combined endovascular and
      surgical approach to thoracoabdominal aortic pathology can be performed in high
      risk patients with acceptable morbidity and mortality. A two-stage approach is
      preferable when extensive coverage of the aorta is necessary and a subcutaneous
      conduit simplifies the second stage. Follow-up of 10 years in our initial patient
      suggests that this approach can be durable. Additional experience and longer
      follow-up is needed before expanding current indications for this approach.

PMID- 19394544
TI  - Endovascular treatment of iliac aneurysm: Concurrent comparison of side branch
      endograft versus hypogastric exclusion.
AB  - OBJECTIVE: To analyze early and mid-term outcome of endovascular treatment in
      patients with iliac aneurysms, comparing the results of hypogastric
      revascularization by branch endografting with those of hypogastric occlusion.
      METHODS: Consecutive patients with iliac aneurysms receiving side branch
      endograft (Group I) were compared with those receiving endograft with hypogastric
      exclusion (Group II) during the interval from January 2000 to May 2008.
      Procedural details and outcomes were prospectively collected and were analyzed at
      one year to avoid mismatch in follow-up length. RESULTS: A total of 74 patients
      (mean age, 75.8 years, 95% males) were treated: 32 in Group I and 42 in Group II.
      No differences in baseline risk factors and aneurysm diameter (40.2 +/- 7.9 mm in
      Group I vs. 38.4 +/- 10.8 in Group II) were found. Concurrent treatment of aortic
      aneurysm was performed in 25/32 (78%) of Group I and 36/42 (86%) of Group II.
      Fluoro time was 48 minutes (interquartile range [IQR] 31-57) in Group I vs. 31
      minutes (IQR 23-38) in Group II (P = .04). The amount of contrast was similar in
      both Groups: 184 ml (IQR 155-210) in Group I vs. 183 ml (IQR 155-200) in Group
      II. No intestinal ischemia or deaths occurred. There were no significant
      differences in failures of hypogastric side branch deployment (2/32) compared
      with hypogastric coiling (3/42). Limb occlusions all occurring in the external
      iliac artery side were 2/32 in Group I vs. 3/42 in Group II. Reintervention rates
      were similar (5/32 vs. 4/42) at one year. Shrinkage of 5 mm or more was detected
      in 7/23 (30%) of Group I and in 13/37 (34%) of Group II. Iliac endoleak was
      present in eight patients (19%) in Group II and in one patient in Group I (4%) (P
      = .1). Similarly, buttock claudication or impotence were more frequent after
      hypogastric exclusion, recorded in eight patients in Group II and in one patient
      in Group I (P = .1). CONCLUSIONS: Endovascular treatment of iliac aneurysm with
      hypogastric revascularization through side branched endografts is feasible and
      safe in the mid-term. When compared with hypogastric embolization, this option
      leads to similar technical success and reintervention rates. Endoleak and buttock
      claudication occur frequently in patients with iliac aneurysm treated with
      hypogastric exclusion, while are uncommon in those with hypogastric
      revascularization. Side branch endografting for iliac aneurysm may be considered
      a primary choice in younger, active patients with suitable anatomy, but larger
      studies and longer postoperative observation periods are needed.

PMID- 19394543
TI  - Systemic inflammation, coagulopathy, and acute renal insufficiency following
      endovascular thoracoabdominal aortic aneurysm repair.
AB  - OBJECTIVE: To characterize the inflammatory and coagulopathic response after
      endovascular thoracoabdominal aortic aneurysm (TAAA) repair and to evaluate the
      effect of the response on postoperative renal function. METHODS: From July 2005
      to June 2008, 42 patients underwent elective endovascular repair of a TAAA using
      custom designed multi-branched stent-grafts at a single academic institution.
      Four patients were excluded from the analysis. White blood cell count (WBC),
      platelet count, prothrombin time (PT), and creatinine were measured in all
      patients. In the last nine patients, interleukin-6 (IL-6), protein C, Factor V, d
      dimers, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) levels
      were also measured. Change in lab values were expressed as a percentage of
      baseline values. RESULTS: The 30-day mortality rate was 5% (2/38). All patients
      (n = 38) had a higher WBC (mean +/- SD: 139 +/- 80%, P < .0001), lower platelet
      count (56 +/- 15%, P < .0001), and higher PT (median: 17%, Interquartile range
      (IQR) 12%-22%, P < .0001) after stent-graft insertion. Twelve of 38 patients
      (32%) developed postoperative acute renal insufficiency (>50% rise in
      creatinine). Patients with renal insufficiency had significantly larger changes
      in WBC (178 +/- 100% vs 121 +/- 64%, P = .04) and platelet count (64 +/- 17% vs
      52 +/- 12%, P = .02) compared with those without renal insufficiency. All
      patients (n = 9) had significant increases in NGAL (182 +/- 115%, P = .008) after
      stent-graft insertion. Six of nine patients (67%) had increased cystatin C (35 +/
      43%, P = .04) after stent-graft insertion, with a greater rise in those with
      postoperative renal insufficiency (87 +/- 32% vs 8 +/- 13%, P = .02). IL-6 levels
      were markedly increased in all patients (n = 9) after repair (9840 +/- 6160%, P =
      .008). Protein C (35 +/- 10%, P = .008) and Factor V levels (28 +/- 20%, P =
      .008) were uniformly decreased, while d-dimers were elevated after repair in all
      patients (310 +/- 213%, P = .008). CONCLUSIONS: Leukocytosis and thrombocytopenia
      were uniform following endovascular TAAA repair, and the severity of the response
      correlated with post-operative renal dysfunction. Elevation of a sensitive marker
      of renal injury (NGAL) suggests that renal injury may occur in all patients after
      stent-graft insertion.

PMID- 19394545
TI  - Metabolic syndrome: A predictor of adverse outcomes after carotid
      revascularization.
AB  - BACKGROUND: Metabolic syndrome (MetS) is rapidly increasing in prevalence and is
      associated with carotid plaque development and is a risk factor for stroke. The
      aim of this study is to describe the outcomes for patients with MetS after
      carotid revascularization (carotid endarterectomy [CEA] and carotid stenting
      [CAS]). METHODS: A database of patients undergoing carotid revascularization for
      primary atherosclerotic lesions was queried from 1996 to 2006. MetS was defined
      as the presence of >or=3 of the following criteria: blood pressure >or=130 mm
      Hg/>or=90 mm Hg; Triglycerides >or=150 mg/dL; high-density lipoproteins (HDL)
      <or=50 mg/dL for women and <or=40 mg/dL for men; fasting blood glucose >or=110
      mg/dL; or Body Mass Index (BMI) >or=30 kg/m(2). Multivariate and Kaplan-Meier
      analyses were performed to outcomes. The average follow-up period was 4.5 years.
      A major adverse event (MAE) was defined as the occurrence of stroke, myocardial
      infarction (MI), or death. RESULTS: A total of 921 patients (mean age: 71 +/- 10
      years; 64% male) underwent 750 CEAs and 171 CAS. Thirty-one percent were
      identified as having MetS, 48% were asymptomatic, 87% had hypertension, 27% had
      hyperlipidemia, 32% were considered diabetic, and 14% had chronic renal
      insufficiency. The morbidity and mortality rates for all patients were 16.9% and
      1.1%, respectively. The 30-day combined stroke/death rate was 3.6%. The 30-day
      MAE rates were: 6.7% vs 3.3% for MetS vs No-MetS (P = .02). The 90-day MAE rates
      were 8.7% vs 4.9% for MetS vs No-MetS (P = .03). MetS patients were more likely
      to experience a complication than No-MetS patients (23% vs 14%, P = .001). By
      Kaplan-Meier analysis, there was no difference between MetS and No-MetS patients
      with respect to patency, restenosis, re-intervention, or survival, but a
      difference existed for freedom from stroke, MI, and MAE. The difference between
      stroke rates was maintained between MetS and No-MetS, when subgrouped by those
      with and without symptoms. For patients with diabetes mellitus (DM), those with
      MetS had a 68% and 410% higher risk of developing an MAE and MI, respectively.
      However, for patients without diabetes, MetS was not significantly associated
      with MAE, stroke, or MI. No factors were found to be significantly associated
      with risk of stroke in all cases (in all patients, patients with diabetes, and
      patients without diabetes). CONCLUSION: MetS is prevalent among patients
      undergoing carotid revascularization. MetS patients are at a greater risk for
      perioperative morbidity as well as stroke, MI, and MAE during follow-up when
      compared to patients without MetS. Long-term stroke prevention is poor in the
      presence of MetS. MetS should be considered a significant risk factor for
      patients undergoing carotid revascularization.

PMID- 19394547
TI  - Functional popliteal artery entrapment syndrome: A poorly understood and often
      missed diagnosis that is frequently mistreated.
AB  - OBJECTIVES: Functional popliteal artery entrapment syndrome (FPAES) is an
      uncommon overuse injury in young physically active adults manifest by
      neuromuscular symptoms (gastroc/soleus cramping, plantar paresthesias). It is
      commonly confused with chronic recurrent exertional compartment syndrome (CRECS).
      This study evaluated the diagnostic testing, mechanism of injury, and treatment
      differences between FPAES and CRECS. METHODS: Between 1987 and 2007, 854 patients
      (557 women, 297 men; mean age, 28.5 years) were surgically treated for the
      diagnosis of CRECS or FPAES, or both. Compartment pressures were measured in all
      patients who had anterior lateral or posterior superficial calf symptoms (normal
      pressure <or=15 mm Hg). Noninvasive stress positional plethysmography was
      routine. Stress positional magnetic resonance imaging (MRI) or angiography (MRA)
      was performed on patients with positive plethysmography result and symptoms
      consistent with FPAES. RESULTS: Of the 854 patients, 757 (95%) had elevated
      compartment pressures (>or=25 mm Hg), and fasciectomy was performed for CRECS
      under local anesthesia (anterior lateral, 508; posterior superficial, 191; distal
      deep posterior, 101). The result of stress plethysmography was positive in 139
      (18%), but they were asymptomatic. Forty-three patients (27 women, 16 men; mean
      age, 26.6 years) had positive stress plethysmography, appropriate FPAES symptoms,
      and normal compartment pressures. MRA/MRI in all 43 demonstrated normal
      musculotendinous anatomy and lateral neurovascular compression with plantar
      flexion. Under general anesthesia, all had excision of the soleal band, with
      relief from symptoms. In 19 of the 43 FPAES patients (44%), CRECS releases were
      done before or after FPAES surgery. Follow-up ranged from 12 to 240 months.
      CONCLUSION: FPAES and CRECS occur in the same population with similar symptoms
      but require different treatment.

PMID- 19394548
TI  - Unmasking pedal arteries in patients with critical ischemia using time-resolved
      contrast-enhanced 3D MRA.
AB  - OBJECTIVE: To test the diagnostic relevance of fast Gadobenate dimeglumine (Gd
      BOPTA) enhanced, time-resolved, three-dimensional magnetic resonance angiography
      (t3D MRA) of distal calf and pedal vasculature in critical limb ischemia in a
      prospective comparison with conventional selective digital subtraction
      angiography (DSA) and high-resolution duplex ultrasound (US) scan. METHODS: From
      April 2007 to June 2008, 34 feet of 29 consecutive patients suffering from limb
      threatening ischemia underwent diagnostic US scan, DSA, and t3D MRA before
      treatment. The investigations took place within 3 days. A t3D MRA was performed
      using a 3 Tesla whole-body magnetic resonance (MR) system with an eight-element
      phased-array coil. Image quality and diagnostic findings were subjectively
      analyzed by two radiologists and one vascular surgeon. Each distal calf and foot
      was divided into six arterial segments for DSA and t3D MRA, and four segments
      were investigated by US scan. Patency or occlusion was studied with all the
      techniques, whereby DSA and t3D MRA were additionally evaluated in patients
      having greater or less than 50% stenosis. Finally, images were visually assessed
      by the three observers by applying a six-point grading scale. The acquired data
      was statistically analyzed using McNemar's test and Wilcoxon's matched-pairs
      signed-rank sum test. The P values of less than an alpha level of .05 were
      considered to be statistically significant. RESULTS: We achieved MRA images of
      diagnostic quality in all patients. Significantly more patent pedal arteries were
      identified by applying t3D MRA than DSA (P < .001) and US scan (P < .02). For
      estimating the degree of stenosis, no technique proved to be superior (P > .28).
      Overall image quality was rated best for t3D MRA. Additionally, potential bypass
      target vessels could be clearly discriminated from pedal veins due to the
      temporal resolution. CONCLUSION: In our prospective study, t3D MRA has been
      proven to be superior to DSA and US scan in pedal vasculature imaging in critical
      limb ischemia. This is a valuable, noninvasive method for detecting potential
      pedal bypass target arteries.

PMID- 19394549
TI  - Midterm results of a precuffed expanded polytetrafluoroethylene graft for above
      knee femoropopliteal bypass in a multicenter study.
AB  - INTRODUCTION: Above knee (AK) femoropopliteal bypass remains a sufficient and
      durable therapy for long occlusions of the superficial femoral artery in the era
      of endovascular repair. A novel, precuffed expanded polytetrafluoroethylene
      (ePTFE) graft that was designed for AK femoropopliteal bypass (Dynaflo, Bard
      Peripheral Vascular Inc, Tempe, Ariz) has been available for clinical use since
      March 2005, promising better patency rates by optimizing the hemodynamic patterns
      within the distal anastomosis. METHODS: A prospective, multicenter, nonrandomized
      study was performed to investigate the clinical results of the Dynaflo graft.
      Primary end points were patency rates, limb salvage, and complications. RESULTS:
      Between March 2005 and August 2007, the Dynaflo graft was used in 135 AK bypasses
      in 134 patients (110 men) with a mean age of 66 years. Indication for
      revascularization was claudication in 99 (73%) and critical ischemia in 36 (27%).
      With a mean follow-up of 18 months the 6-, 12- and 24-month primary patency rates
      were 90%, 83% and 72.5% and the secondary patency rates were 93%, 88.6% and
      82.2%, respectively. The cumulative limb salvage rate at 24 months was 95%.
      Complications were observed in 39 patients (29%), with bypass failure (29 cases)
      and significant thrombus accumulation at the distal anastomosis (4 cases) being
      the most severe. CONCLUSION: This study presents the first clinical results of a
      novel ePTFE graft for supragenicular revascularization. The implantation of the
      Dynaflo graft seems to be safe and feasible for AK bypass, achieving acceptable
      medium-term patency rates. Nevertheless, long-term results have to be awaited,
      and prospective comparative studies are warranted.

PMID- 19394550
TI  - Heparin-bonded ePTFE grafts compared with vein grafts in femoropopliteal and
      femorocrural bypasses: 1- and 2-year results.
AB  - OBJECTIVE: Many patients with peripheral arterial occlusive disease who require a
      lower-limb bypass have no available autologous saphenous vein (ASV) for the
      procedure and thus require a prosthetic graft. Expanded polytetrafluoroethylene
      (ePTFE) grafts are commonly used, but results with these prostheses have varied,
      especially when the distal anastomosis is below the knee. However, there is
      increasing evidence that ePTFE grafts to which heparin has been bound with use of
      covalent endpoint linkage provide better results. This nonrandomized study
      compared the performance of these grafts with that of ASV conduits in the largest
      clinical series of heparin-bonded ePTFE graft implantations reported so far.
      METHODS: The records of 350 patients who underwent a lower-limb bypass procedure
      that used either a heparin-bonded ePTFE graft (n = 240) or an ASV graft (n = 110)
      were reviewed, and preoperative, operative, and follow-up data were recorded.
      Kaplan-Meier analyses were used to calculate primary patency and limb salvage
      rates in the two graft groups; results were compared by using log-rank testing.
      RESULTS: The primary patency rates at 1 year for the heparin-bonded ePTFE grafts
      were 92% for above-knee femoropopliteal (AK FP) bypasses, 92% for below-knee
      femoropopliteal (BK FP) bypasses, and 79% for femorocrural (FC) applications. The
      corresponding 2-year rates were 83%, 83%, and 69%, respectively. In the ASV
      group, the 1-year primary patency rates for AK FP, BK FP, and FC bypasses were
      91%, 72%, and 69%, respectively; the 2-year rates were 80%, 72%, and 64%,
      respectively. There were no significant differences in patency when AK FP, BK FP,
      or FC procedures were considered separately. Two-year limb salvage rates in the
      heparin-bonded ePTFE graft group were 92%, 98%, and 87%, respectively, for AK FP,
      BK FP, and FC bypasses; in the ASV group, the rates were 100%, 91%, and 96%,
      respectively. Two infections occurred in patients given a heparin-bonded ePTFE
      graft. CONCLUSION: In this large retrospective study, heparin-bonded ePTFE grafts
      had 1- and 2-year primary patency results that were not significantly different
      from those for ASV grafts. Results in BK FP and FC applications were especially
      promising. Randomized studies comparing the use of heparin-bonded ePTFE and ASV
      grafts in the treatment of peripheral arterial disease are needed to substantiate
      our results.

PMID- 19394551
TI  - Invasive treatment of claudication is indicated for patients unable to adequately
      ambulate during cardiac rehabilitation.
AB  - BACKGROUND: Cardiac rehabilitation (CR) is of proven benefit for patients with
      coronary artery disease. Patients who successfully complete CR have a
      statistically significant reduction in the risk of fatal myocardial infarction
      (MI) and all-cause mortality. Peripheral arterial disease (PAD) is common in
      patients with coronary artery disease. OBJECTIVES: We investigated whether PAD
      prevents the successful completion of CR and cardiac risk reduction and whether
      invasive treatment of claudicant patients who cannot walk sufficiently to
      successfully complete CR is indicated. METHODS: The records of 230 consecutive CR
      patients were reviewed for attendance, target heart rate, and Walking Impairment
      Questionnaire (WIQ) values to compare PAD among successes and failures. Failure
      of CR was defined as inability to walk sufficiently to achieve target heart rate.
      Markov decision analysis using published data for endovascular and open
      intervention for claudication was used to compare outcomes of treatment
      strategies in which PAD is untreated (current standard), PAD is treated only if
      it interfered with CR, and treatment of PAD in all patients before initiating CR.
      RESULTS: Of 230 patients, 126 had complete records for analysis. Ankle-brachial
      indices (ABIs) were documented for 39 patients. Overall, 40% of patients failed
      CR. Failure was significantly more common in patients with claudication (76%)
      than in those without (26%; odds ratio [OR], 8.9; 95% confidence interval [CI],
      3.7-21.7; P < .001). The presence of PAD, determined by the WIQ walking distance
      score, was significantly higher in the failure group (34%) vs the success group
      (17%; OR, 2.5; 95% CI, 1.1-6.0; P = .03). The presence of PAD, determined by ABI,
      was higher in the failure group (39%) vs the success group (14%; OR, 3.8; 95% CI,
      0.8-17.9; P = .08). Logistic regression analysis when CR failure was adjusted for
      age and gender was significantly associated with presence of PAD based on WIQ
      walking distance score (OR, 2.8; 95% CI 1.1-7.1; P = .03). A strategy of invasive
      therapy only if PAD interfered with the successful completion of CR would save an
      additional 54 lives per 10,000 patients compared with no intervention.
      CONCLUSIONS: PAD is a significant cause of CR failure, preventing patients from
      successfully completing the program and achieving a reduction in risk of fatal
      cardiac events. Invasive treatment of PAD in patients who fail CR is indicated,
      with an expected lifesaving outcome.

PMID- 19394553
TI  - Compression therapy in breast cancer-related lymphedema: A randomized, controlled
      comparative study of relation between volume and interface pressure changes.
AB  - OBJECTIVE: Short stretch bandages are very effective in the initial management of
      arm lymphedema. However, no studies to date have measured the pressure required
      to achieve specific amounts of volume reduction. The purpose of this study was to
      determine whether there is a difference between low and high-pressure bandaging
      in terms of therapeutically intended volume reduction of the compressed arm.
      METHODS: Experimental, randomized and comparative study with two study-groups
      consisting of high and low initial interface pressure bandages. Thirty-six
      hospitalized patients in Nij Smellinghe hospital suffering from moderate to
      severe unilateral breast cancer-related lymphedema not responsive to outpatient
      treatment were included. Bilateral arm volume was measured by inverse water
      volumetry before, after two hours and after 24 hours of bandaging. The amount of
      edema was calculated by subtracting the volume of the diseased arm from that of
      the contralateral side. Sub-bandage pressure was measured after bandage
      application and two hours later. Bandages were then re-applied and the pressure
      was measured again. Twenty-four hours later, the pressure measurement was
      repeated and bandages were removed for final volumetry. Patients were randomized
      into two groups: group A received low pressure bandages (20-30 mm Hg) and group B
      received high pressure bandages (44-58 mm Hg). The main outcome measures were
      reduction of arm volume and edema volume in the affected arm in both study
      groups. Secondary outcome parameters were changes in sub-bandage pressure and
      patient comfort. RESULTS: Median arm volume reduction after two and 24 hours was
      104.5 mL (95% confidence interval [CI], 51.2-184.2) (-2.5%) (P < .0001) and 217
      mL (95% CI, 143.9-280.2) (-5.2%) (P < .01) for group A and 56.5 mL (95% CI, -2.7
      123.1) (n.s.) and 167.5 mL (95% CI, 105.2-316.1) (-4.2%) (P < .01) for group B,
      respectively. There was no statistically significant difference between the
      volume changes in group A and group B. After 24 hours, edema decreased by median
      percentage of 9.2% in group A and 4.8% in group B (n.s.). Bandages in group A
      were better tolerated. The sub-bandage pressure drop in the first two hours was
      between 41% and 48% in both treatment groups at both measuring sites. After 24
      hours, the pressure drop was between 55% and 63%. No proximal swelling above the
      bandage was observed. CONCLUSIONS: Inelastic, multi-layer, multi-component
      compression bandages with lower pressure (20-30 mm Hg) are better tolerated and
      achieve the same amount of arm volume reduction as bandages applied with higher
      pressure (44-58 mm Hg) in the first 24 hours.

PMID- 19394554
TI  - Characterization of primary and restenotic atherosclerotic plaque from the
      superficial femoral artery: Potential role of Smad3 in regulation of SMC
      proliferation.
AB  - OBJECTIVE: To characterize and compare primary and restenotic lesions of the
      superficial femoral artery and analyze the contribution of TGF-beta/Smad3
      signaling to the pathophysiology of peripheral artery occlusive disease. METHODS
      AND RESULTS: Immunohistochemical studies were performed on specimens retrieved
      from the superficial femoral artery of patients undergoing either atherectomy for
      primary atherosclerotic or recurrent disease after stenting and/or prior
      angioplasty. Immunohistochemical analysis revealed a significantly higher smooth
      muscle cell (SMC) content (alpha-actin+) and expression of Smad3 in restenotic
      lesions while primary lesions contained significantly more leukocytes (CD45+) and
      macrophages (CD68+). Further studies demonstrated colocalization of Smad3 with
      alpha-actin and PCNA, suggesting a role for Smad3 in the proliferation observed
      in restenotic lesions. To confirm a role for Smad3 in SMC proliferation, we both
      upregulated Smad3 via adenoviral mediated gene transfer (AdSmad3) and inhibited
      Smad3 through transfection with siRNA in human aortic SMCs, then assessed cell
      proliferation with tritiated thymidine. Overexpression of Smad3 enhanced whereas
      inhibition of Smad3 decreased cell proliferation. CONCLUSION: Differences in
      cellular composition and cell proliferation in conjunction with the finding that
      Smad3 is expressed exclusively in restenotic disease suggest that TGF-beta,
      through Smad3 signaling, may play an essential role in SMC proliferation and the
      pathophysiology of restenosis in humans.

PMID- 19394555
TI  - Cell migration in response to the amino-terminal fragment of urokinase requires
      epidermal growth factor receptor activation through an ADAM-mediated mechanism.
AB  - BACKGROUND: Cell migration is an integral component of intimal hyperplasia
      development and proteases are pivotal in the process. Understanding the role of
      urokinase signaling within the cells of vasculature remains poorly defined. The
      study examines the role of amino-terminal fragment (ATF) of urokinase on a
      pivotal cross-talk receptor, epidermal growth factor receptor (EGFR). EGFR is
      transactivated by both G-protein-coupled receptors and receptor tyrosine kinases
      and is key to many of their responses. We hypothesize that A Disintegrin and
      Metalloproteinase Domains (ADAM) allows the transactivation of EGFR by ATF.
      OBJECTIVE: To determine the role of ADAM in EGFR transactivation by ATF in human
      vascular smooth muscle cells (VSMC) during cell migration. METHODS: Human
      coronary VSMC were cultured in vitro. Assays of EGFR phosphorylation were
      examined in response to ATF (10 nM) in the presence and absence of the matrix
      metalloprotease (MMP) inhibitor GM6001, the ADAM inhibitors TAPI-0 and TAPI-1,
      heparin binding epidermal growth factor (HB-EGF) inhibitor, CRM197, HB-EGF
      inhibitory antibodies, epidermal growth factor (EGF) inhibitory antibodies, and
      the EGFR inhibitor AG1478. The small interference ribonucleic acid (siRNA)
      against EGFR and ADAM-9, ADAM-10, ADAM-12, and adenoviral delivered Gbg
      inhibitor, betaARK(CT) were also used. RESULTS: ATF produced concentration
      dependent VSMC migration (by wound assay and Boyden chamber), which was inhibited
      by increasing concentrations of AG1478. ATF was shown to induce time-dependent
      EGFR phosphorylation, which peaked at fourfold greater than control. Pre
      incubation with the Gbetagamma inhibitor betaARK(CT) inhibited EGFR activation by
      ATF. This migratory and EGFR response was inhibited by AG1478 in a concentration
      dependent manner. Incubation with siRNA against EGFR blocked the ATF-mediated
      migratory and EGFR responses. EGFR phosphorylation by ATF was blocked by
      inhibition of MMP activity and the ligand HB-EGF. The presence of the ADAM
      inhibitors, TAPI-0 and TAPI-1 significantly decreased EGFR activation. EGFR
      phosphorylation by EGF was not interrupted by inhibition of MMP, ADAMs, or HB
      EGF. Direct blockade of the EGFR prevented activation by both ATF and EGF.
      Incubation with siRNA to ADAM-9 and -10 significantly reduced HB-EGF release from
      VSMC and EGFR activation in response to ATF. The siRNA against ADAM-12 had no
      effect. CONCLUSION: ATF can induce transactivation of EGFR by an ADAM-mediated,
      HB-EGF-dependent process. Targeting a pivotal cross-talk receptor such as EGFR is
      an attractive molecular target to inhibit cell migration.

PMID- 19394556
TI  - Incidental finding of malignancy in patients preoperatively evaluated for
      aneurysm wall pathology using PET/CT.
AB  - Preoperative positron emission tomography/computed tomography (PET/CT) was
      performed in 26 consecutive patients considered fit for aneurysm repair. Besides
      information on aneurysm wall pathology, PET/CT identified 6 patients with
      concomitant malignancy. As a result of this coincidental finding, the operation
      was postponed in 2 patients and cancelled in 1. Although previous studies have
      shown that PET/CT might affect patient selection based on aneurysm wall
      inflammation, our preliminary results show a big impact on patient management as
      a result of the sensitivity of PET/CT for detecting malignancy. Future larger
      studies are warranted to investigate the effect and cost effectiveness of routine
      PET/CT in abdominal aortic aneurysm (AAA) patients.

PMID- 19394557
TI  - Nonmaturation of arm arteriovenous fistulas for hemodialysis access: A systematic
      review of risk factors and results of early treatment.
AB  - INTRODUCTION: Arteriovenous fistula (AVF) nonmaturation increases reliance of
      hemodialysis patients on grafts and catheters, exposing them to associated high
      complication risks. This systematic review assessed the success rates and
      complications of therapeutic interventions in arm hemodialysis AVFs experiencing
      nonmaturation. It also compared the efficacy of preoperative clinical factors
      (eg, age, gender, race), and preoperatively and postoperatively acquired
      hemodynamic parameters (eg, arterial diameter or blood flow through the AVF) at
      stratifying risk of nonmaturation. METHODS: Two independent researchers used a
      systematic strategy to search literature databases and extract data from articles
      judged relevant and valid. The evidence base for this review comprised 33
      articles, 12 about treatment, and 21 concerning risk stratification. A meta
      analysis was performed to calculate summary measures for nonmaturation treatment
      success and risk stratification efficacy (eg, excess risk and relative risk) of
      preoperative clinical, preoperative hemodynamic, and postoperative hemodynamic
      risk factors. RESULTS: The success rate of early endovascular or surgical
      treatment, defined as the possibility of achieving adequate hemodialysis,
      averaged 86%, with 1-year primary patencies of 51%, 1-year secondary patencies of
      76%, and complication rates of 9.3%, with 5.5% minor complications. Overall,
      patients with preoperative clinical risk factors had excess nonmaturation risks
      of 21% (95% confidence interval [CI], 11%-30%) and a relative risk of 1.7 (95%
      CI, 1.3-2.1). Patients with preoperative hemodynamic risk factors had average
      estimated excess risks of 24% (95% CI, 15%-33%) and a relative risk of 1.7 (95%
      CI, 1.4-2.0). Patients with hemodynamic risk factors present shortly after
      operation had excess nonmaturation risks of 50% (95% CI, 42%-58%) and a relative
      risk of 4.3 (95% CI, 3.4-5.5). CONCLUSIONS: Patients can be treated effectively
      for AVF nonmaturation early on, and it is possible to identify those patients at
      risk of nonmaturation most effectively with an early postoperative assessment of
      hemodynamic risk factors. Additional research is needed that concentrates on
      adopting the strategy of early treatment of patients with postoperative risk
      factors.

PMID- 19394558
TI  - To transfer or not to transfer, that is the question.
AB  - An elderly patient who underwent a complex emergency abdominal aneurysmectomy two
      weeks ago is in coma, ventilator dependent, and in severe multisystem organ
      failure with a deteriorating prognostic index score. The family has become
      increasingly hostile towards Dr S. Cold, the consultants, the ICU nurses, and the
      janitorial staff. An estranged wife has called once to defer decision-making to
      the children. Three children intermittently visit and are openly critical of the
      medical care. One child is an ICU nurse supervisor at a small local suburban
      hospital. Dr Cold spoke to the family yesterday about instituting DNR orders and
      discontinuing some supportive therapy that was not working. The family first
      required another consultation and then demanded that Dr Cold transfer the patient
      to the hospital where the daughter works. The hospital does not provide tertiary
      care. A physician there is willing to assume responsibility. How should Dr Cold
      respond? A. Do as they request. B. Refuse outright. C. Call the accepting
      physician and explain why the case is futile. D. Take the matter to the ethics
      committee to prevent transfer. E. Call the wife and children to schedule an
      exploratory family conference and insist they come to a decision.

PMID- 19394559
TI  - What a vascular surgeon should know and do about atherosclerotic risk factors.
AB  - Atherosclerosis is a systematic disease presenting with a significant overlapping
      of cardiovascular disorders implicating coronary heart disease and its
      equivalents, peripheral arterial disease, carotid arterial disease, and aneurysm
      disease. Evaluating patient's atherosclerotic risk profile is essential to guide
      primary and secondary prevention. Atherosclerotic risk factor modifications
      reduce, significantly, cardiovascular disease mortality and morbidity,
      particularly in high-risk patients. This article provides a reference guide for
      all conventional (eg, smoking, dyslipidemia, hypertension) and evolving (eg,
      homocysteine, C-reactive protein, fibrinogen, inflammatory markers) risk factors
      of atherosclerosis and recommends the currently effective strategies for an
      overall cardiovascular risk reduction. As vascular surgeons, by definition,
      conduct the overall management of patients with vascular disease understanding of
      the development, assessment, and management of atherosclerotic risk factors
      should remain among their highest priorities.

PMID- 19394562
TI  - Regarding "Arterial trauma during central venous catheter insertion: Case series,
      review, and proposed algorithm".

PMID- 19394563
TI  - Regarding "Trends and outcomes of concurrent carotid revascularization and
      coronary bypass".

PMID- 19394564
TI  - Utilization of imaging: challenges and opportunities.

PMID- 19394565
TI  - The changing face of health technology assessment.

PMID- 19394566
TI  - Impact of the ABR examination changes on residency.

PMID- 19394567
TI  - Cardiac MRI: will coverage ever flow?

PMID- 19394568
TI  - Educating for artistry.

PMID- 19394569
TI  - Introduction: health technology assessment in diagnostic imaging.

PMID- 19394570
TI  - Health technology assessment for radiologists: basic principles and evaluation
      framework.
AB  - Decision makers are faced with the task of allocating health resources to
      maximize patients' health under budget constraints. To offer structure to the
      complexity of the decision-making process, the field of health technology
      assessment (HTA) was developed. This paper offers an introduction to the
      fundamental aspects of HTA and acts as a guide to the conduct of HTA for
      radiologists. First, the authors define HTA and describe how it is linked to the
      field of diagnostics. Second, a basic 11-step framework for the conduct of an HTA
      is outlined. The framework begins with the identification of the problem and
      proceeds through to the dissemination and impact of an HTA. Third, the authors
      provide a real-world example of an HTA in the field of diagnostics. Last, they
      describe the challenges and barriers faced in HTA.

PMID- 19394571
TI  - Approaches for economic evaluations of health care technologies.
AB  - Economic evaluations involve the comparison of alternative courses of action in
      terms of both their costs and their consequences. In response to increasing
      health care costs, economic evaluations of competing technologies, including
      radiologic interventions, are increasingly used to inform resource allocation
      decisions. It is therefore crucial that radiologists have a thorough
      understanding of the methods. The objective of this paper is to present a
      detailed overview of the principles and methods of economic evaluations of health
      technologies, including recent methodologic developments. For the purpose of this
      paper, the key elements of an economic evaluation are divided into 5 broad
      sections: 1) types of economic evaluations (eg, cost-effectiveness analysis, cost
      utility analysis), 2) study perspectives (ie, temporal and cost perspectives), 3)
      analysis of costs and effects (eg, incremental cost-effectiveness ratios, cost
      effectiveness planes), 4) conducting economic evaluations alongside trials or
      using decision-analytic models, and 5) dealing with the different forms of
      uncertainty in economic evaluations (eg, sampling uncertainty in trials,
      parameter uncertainty in models). Examples from the recent radiology literature
      are used to explain the key concepts. This review improves upon the previous
      educational papers published in radiologic journals, as it covers recent
      methodologic advances regarding the treatment of uncertainty.

PMID- 19394572
TI  - Illustrating economic evaluation of diagnostic technologies: comparing
      Helicobacter pylori screening strategies in prevention of gastric cancer in
      Canada.
AB  - OBJECTIVE: The aim of this paper is to present an economic evaluation of
      diagnostic technologies using Helicobacter pylori screening strategies for the
      prevention of gastric cancer as an illustration. METHODS: A Markov model was
      constructed to compare the lifetime cost and effectiveness of 4 potential
      strategies: no screening, the serology test by enzyme-linked immunosorbent assay
      (ELISA), the stool antigen test (SAT), and the (13)C-urea breath test (UBT) for
      the detection of H. pylori among a hypothetical cohort of 10,000 Canadian men
      aged 35 years. Special parameter consideration included the sensitivity and
      specificity of each screening strategy, which determined the model structure and
      treatment regimen. The primary outcome measured was the incremental cost
      effectiveness ratio between the screening strategies and the no-screening
      strategy. Base-case analysis and probabilistic sensitivity analysis were
      performed using the point estimates of the parameters and Monte Carlo
      simulations, respectively. RESULTS: Compared with the no-screening strategy in
      the base-case analysis, the incremental cost-effectiveness ratio was $33,000 per
      quality-adjusted life-year (QALY) for the ELISA, $29,800 per QALY for the SAT,
      and $50,400 per QALY for the UBT. The probabilistic sensitivity analysis revealed
      that the no-screening strategy was more cost effective if the willingness to pay
      (WTP) was <$20,000 per QALY, while the SAT had the highest probability of being
      cost effective if the WTP was >$30,000 per QALY. Both the ELISA and the UBT were
      not cost-effective strategies over a wide range of WTP values. CONCLUSION:
      Although the UBT had the highest sensitivity and specificity, either no screening
      or the SAT could be the most cost-effective strategy depending on the WTP
      threshold values from an economic perspective. This highlights the importance of
      economic evaluations of diagnostic technologies.

PMID- 19394573
TI  - Conditionally funded field evaluations and practical trial design within a health
      technology assessment framework.
AB  - Randomized controlled trials may lack generalizability and cannot always provide
      sufficient information for policymakers to make decisions regarding the use of
      new technologies entering into a health care system. Information related to other
      aspects of health technologies, in addition to clinical endpoints, such as
      economic, patient-related, and organizational issues, may be needed before making
      policy decisions. To address generalizability issues related to a health care
      technology, primary data collection conducted within a health care system may be
      required. A process for primary data collection to inform health policy in
      Ontario regarding health care technologies was initiated in 2003. Following
      recommendations from the Ontario Health Technology Advisory Committee,
      conditionally funded field evaluations for promising technologies with
      insufficient information are initiated. The conduct of these field evaluations
      occurs in 3 stages. The translation of the policy problem to research questions
      that can be answered through the design of a practical clinical trial is the
      first stage, followed by implementation, data collection, quality control, and
      quality assurance activities. After the completion of the field evaluation data
      collection and analysis, the results of the study are presented to the committee
      to respond to its request. Technologies evaluated by this process include drug
      eluting stents, the endovascular repair of abdominal aortic aneurysms, and
      multifaceted interventions in diabetes care. This process, developed in Ontario
      for the evaluation of health technologies, has been a successful collaborative
      effort between practitioners, academia, government, health policymakers, and
      industry that has permitted an evidence-based framework for the approval and
      funding of technologies within the health care system.

PMID- 19394574
TI  - Health technology assessment and primary data collection for reducing uncertainty
      in decision making.
AB  - BACKGROUND: Health care expenditures continue to escalate, and pressures for
      increased spending will continue. Health care decision makers from publicly
      financed systems, private insurance companies, or even from individual health
      care institutions, will continue to be faced with making difficult purchasing,
      access, and reimbursement decisions. As a result, decision makers are
      increasingly turning to evidence-based platforms to help control costs and make
      the most efficient use of existing resources. Most tools used to assist with
      evidence-based decision making focus on clinical outcomes. HEALTH TECHNOLOGY
      ASSESSMENT: Health technology assessment (HTA) is increasing in popularity
      because it also considers other factors important for decision making, such as
      cost, social and ethical values, legal issues, and factors such as the
      feasibility of implementation. In some jurisdictions, HTAs have also been
      supplemented with primary data collection to help address uncertainty that may
      still exist after conducting a traditional HTA. ROLE OF PRIMARY DATA COLLECTION:
      The HTA process adopted in Ontario, Canada, is unique in that assessments are
      also made to determine what primary data research should be conducted and what
      should be collected in these studies. In this article, concerns with the
      traditional HTA process are discussed, followed by a description of the HTA
      process that has been established in Ontario, with a particular focus on the data
      collection program followed by the Programs for Assessment of Technology in
      Health Research Institute. An illustrative example is used to show how the
      Ontario HTA process works and the role value of information analyses plays in
      addressing decision uncertainty, determining research feasibility, and
      determining study data collection needs.

PMID- 19394575
TI  - Health technology assessment: a review of international activity and examples of
      approaches with computed tomographic colonography.
AB  - The growth of health technology assessment (HTA) internationally is currently
      reflected in the growing membership of the International Network of Agencies for
      Health Technology Assessment. Many national and regional HTA institutions emerged
      in the 1980s and 1990s, and more recently, HTA has emerged in newly
      industrialized countries and in European Union member states in transition.
      Health technology assessment activities are becoming an increasingly important
      part of health care culture, with the appearance of HTA units in hospitals and
      hospital departments. This article provides a brief overview of who conducts HTA
      internationally and looks at how HTA is conducted and how this information is
      used. To highlight the different structures, processes, and methods available, a
      portion of this article is dedicated to describing different approaches that have
      been observed with respect to the assessment of computed tomographic colonography
      in North America for population-based colorectal cancer screening.

PMID- 19394576
TI  - Health technology assessment from a Canadian device industry perspective.
AB  - Health technology assessment has significantly improved the decision-making
      process via the thorough and systematic evaluation of the clinical utility and
      cost-effectiveness of new drugs and health technologies. However, the device
      industry faces a significant challenge in meeting the evidentiary demands of the
      health technology assessment process, particularly given the small size of the
      Canadian market and device manufacturers. This is further compounded by the
      somewhat short-sighted nature of health care budgets, which see medical devices
      as a cost-driver given the sometimes significant upfront investment required to
      implement a technology producing downstream benefits in the long-term. Industry
      is the research and development of the health care system, but innovative
      development could be stifled unless the health technology assessment process
      recognizes the risk of manufacturers. The authors propose that health technology
      assessment can be improved by recognizing the challenges that device
      manufacturers face and by sharing the risk associated with evaluations of
      effectiveness. Health technology assessment is a powerful tool that can be used
      to evaluate new and potentially obsolete technologies alike, with the goal of
      meeting the needs of patients as customers of both the device industry and the
      health care system.

PMID- 19394577
TI  - The National Oncologic PET Registry: lessons learned for coverage with evidence
      development.
AB  - The National Oncologic PET Registry (NOPR) was one of the first attempts of the
      Centers for Medicare & Medicaid Services (CMS) at coverage with evidence
      development. Under this coverage policy, the agency will provide payment for a
      technology only if patients and providers agree to enroll in a prospective study
      or registry. The NOPR was designed to determine if the results of positron
      emission tomography scans influence physicians' intended plans of patient
      management while imposing minimal restrictions on the use of such scans in the
      clinical setting. The experience of policymakers, methodologists, physicians, and
      patients with the NOPR provides some useful insights into the utility and
      challenges of implementing, financing, and creating a robust methodology for
      coverage with evidence development in the future. Moving to a system of evidence
      based medical technology diffusion will require all health care decision makers
      to become involved in evidence generation and reach an agreement about the type
      of evidence required to make informed medical decisions.

PMID- 19394578
TI  - Applying evidence-based imaging to policy: the Washington State experience.
AB  - In response to escalating medical costs and a lack of evidence supporting some
      medical procedures, the state of Washington initiated a new program to use
      evidence-based medicine to determine if medical technologies should be covered
      for reimbursement by state agencies. The Washington State Health Technology
      Assessment Program was formed to commission evidence reports on selected
      technologies and to determine reimbursement on the basis of evidence of
      effectiveness, safety, and cost-effectiveness. To date, the program has reviewed
      the imaging technologies of upright magnetic resonance imaging, computed
      tomographic colonography, and lumbar discography and has not found sufficient
      evidence to support reimbursement. This report details the structure of the
      program, the reasons for the committee's decisions, and the implications for
      radiology. Under the Washington model, stronger evidence for the effectiveness,
      safety, and cost-effectiveness of imaging will be required for the dissemination
      of new technologies and for reimbursement for some existing imaging approaches.

PMID- 19394579
TI  - Significant payment decreases to freestanding cancer centers that provide high
      dose-rate brachytherapy.

PMID- 19394580
TI  - The ACR needs you: serve as a resident grassroots committee liaison.

PMID- 19394581
TI  - Cystic pancreatic lesions: classification and management.

PMID- 19394582
TI  - William E. Allen Jr.

PMID- 19394583
TI  - Payment for x-ray interpretation in the ED: solving the dilemma.

PMID- 19394584
TI  - Re: "Payment for x-ray interpretation in the ED: solving the dilemma".

PMID- 19394585
TI  - Averageness or symmetry: which is more important for facial attractiveness?
AB  - Effects of averageness and symmetry on the judgment of facial attractiveness were
      investigated using a generalized Procrustes method and multiple regression
      analyses. Participants (n=114) rated attractiveness of 96 photographs of faces
      with neutral expressions. Through a generalized Procrustes method, the faces and
      their mirror-reversed versions were represented as points on a hyperplane. Both
      averageness and symmetry of each individual were defined as distances on the
      plane. A multiple regression analysis was performed to examine the effect of
      symmetry and averageness for each gender. For male faces, both symmetry and
      averageness affected attractiveness ratings positively , and there was no
      difference between the effects of averageness and symmetry. On the other hand,
      for female faces only averageness affected attractiveness, whereas symmetry did
      not. However, these effects were not large.

PMID- 19394586
TI  - Chlorhexidine and evidence-based labor management.

PMID- 19394587
TI  - The risk of cerebral palsy in survivors of multiple pregnancies with cofetal loss
      or death.
AB  - OBJECTIVE: This study investigated the risks for cerebral palsy in survivors of
      multiple pregnancies with cofetal loss (< 20 weeks' gestation) or cofetal death
      (>or= 20 weeks' gestation). STUDY DESIGN: The total Western Australian population
      based case-control study included 741 cases of cerebral palsy. RESULTS: Antenatal
      cofetal loss or death occurred in 3% of all cases of cerebral palsy, which is a
      small but significant contribution. The odds ratio for cerebral palsy in
      survivors of cofetal loss that included iatrogenic pregnancy reduction was 2.65
      (95% confidence interval [CI], 0.78-8.98), which gave a population-attributable
      proportion of 7.28% (95% CI, 0-27.5), compared with 4.25 (95% CI, 1.12-16.10) and
      10.6% (95% CI, 1.0-35.6) for survivors of cofetal death. CONCLUSION: This study
      quantifies the contribution of cofetal death to cerebral palsy and suggests that
      cofetal loss makes a similar, although somewhat smaller, contribution to the risk
      for cerebral palsy in survivors of multiple pregnancies.

PMID- 19394588
TI  - Final pH affects the interference capacity of naturally occurring oral
      Lactobacillus strains against mutans streptococci.
AB  - OBJECTIVES: To establish the effects of three factors: previous caries
      experience; colonization of Streptococcus mutans; and final pH on autologous
      lactobacilli-mediated inhibition against a panel of mutans streptococci in young
      subjects with different caries experiences. DESIGN: The inhibition capacity was
      determined by the use of the agar overlay method and the final pH in culture
      medium was measured after 20 h. Using a logistic regression model, the risk of
      having an incomplete lactobacilli-mediated inhibition was calculated. RESULTS:
      All three factors significantly influenced the interference outcome in the order;
      final pH of the Lactobacillus strains, oral colonization of autologous S. mutans
      and caries experience. A high risk occurred at a lower pH and at a wider pH range
      for individuals with previous caries experience and autologous colonization of S.
      mutans compared with caries-free subjects who were not colonized. At a final pH
      of 4.0, this risk was approximately eight times higher than that of the latter
      group. Two mutans Streptococcus strains in the test panel demonstrated high
      individual predictive values of inhibition mediated by oral lactobacilli.
      CONCLUSIONS: Generation of a low pH either directly via organic acid production
      and/or production of bacteriocins or metabolites at a low pH may promote mutans
      Streptococcus growth inhibition, in vitro. Furthermore, a shift of pH range for
      the risk of incomplete inhibition of mutans streptococci suggests a less
      effective inhibition at a wider pH range for naturally occurring lactobacilli
      from individuals with earlier caries experience containing own S. mutans.

PMID- 19394589
TI  - The centrality of a loss and its role in emotional problems among bereaved
      people.
AB  - In literature on posttraumatic stress-disorder (PTSD) there is growing interest
      in the concept "centrality of event", referring to the degree to which the memory
      of a traumatic event is central to one's everyday inferences, life-story, and
      identity. Using self-reported data from 254 bereaved individuals, this study
      examined the centrality of the loss-event in emotional problems following loss.
      Findings showed that this centrality (a) varied as a function of kinship to the
      deceased but not other loss-related variables, (b) was correlated with
      complicated grief (CG), depression, PTSD, and with neuroticism and several
      cognitive-behavioural variables, and (c) remained correlated with CG but not
      depression and PTSD when controlling for the shared variance between these
      symptoms, neuroticism, and these cognitive-behavioural variables.

PMID- 19394590
TI  - Physicochemical features of ultra-high viscosity alginates.
AB  - The physicochemical characteristics of the ultra-high viscosity and highly
      biocompatible alginates extracted from Lessonia nigrescens (UHV(N)) and Lessonia
      trabeculata (UHV(T)) were analyzed. Fluorescence and (1)H NMR spectroscopies,
      viscometry, and multi-angle light scattering (MALS) were used for elucidation of
      the chemical structure, molar mass, and coil size. The sequential structures from
      NMR spectroscopy showed high guluronate content for UHV(T), but low for UHV(N).
      Intrinsic viscosity [eta] measurements exhibited unusual high values (up to 2750
      mL/g), whereas [eta] of a commercial alginate was only about 970 mL/g. MALS batch
      measurements of the UHV-alginates yielded ultra-high values of the weight average
      molar mass (M(w) up to 1.1x10(6) g/mol) and of the z-average gyration radius
      (R(G)(z) up to 191 nm). The M(w) and R(G)(z) distributions of UHV-alginates and
      of ultrasonically degraded fractions were determined using size exclusion
      chromatography combined with MALS and asymmetrical flow-field-flow fractionation.
      The M(w) dependency of [eta] and R(G)(z) could be described by
      [eta]=0.059xM(w)(0.78) and R(G)(z)=0.103xM(w)(x). (UHV(N): x=0.52; UHV(T):
      x=0.53) indicating that the monomer composition has no effect on coil expansion.
      Therefore, the equations can be used to calculate M(w) and R(G)(z) values of
      UHV(T)- and UHV(N)-alginate mixtures as used in immunoisolation. Furthermore, the
      simple and inexpensive capillary viscometry can be used for real-time validation
      of the extraction and purification process of the UHV-alginates.

PMID- 19394591
TI  - Structural determination of the O-antigenic polysaccharide from Salmonella Mara
      (O:39).
AB  - The O-antigenic polysaccharide of Salmonella Mara O:39 (formerly Q) was
      investigated by sugar and methylation analyses, absolute configuration
      assignment, mass spectrometry and NMR spectroscopy. The experiments revealed an O
      polysaccharide chain composed of the following linear tetrasaccharide repeating
      units with the structure: -->2)-alpha-L-Quip3NAc-(1-->3)-alpha-D-Manp-(1-->3)
      alpha-L-Fucp-(1-->3)-alpha-D-GalpNAc-(1--> where alpha-L-Quip3NAc is the residue
      of 3-acetamido-3,6-dideoxy-alpha-L-glucopyranose. This repeating unit is the
      first published structure of the O-polysaccharide from 27 serotypes of Salmonella
      bacteria belonging to serogroup O:39 in the Kauffmann-White classification
      system.

PMID- 19394592
TI  - Human monocytes but not dendritic cells are killed by blocking of autocrine
      cyclooxygenase activity.
AB  - Dendritic cells (DCs), in peripheral tissues, derive mostly from blood precursors
      that differentiate into DCs under the influence of the local microenvironment.
      Monocytes constitute the main known DC precursors in blood and their infiltration
      into tissues is up-regulated during inflammation. During this process, the local
      production of mediators, like prostaglandins (PGs), influence significantly DC
      differentiation and function. In the present paper we show that treatment of
      blood adherent mononuclear cells with 10microM indomethacin, a dose achieved in
      human therapeutic settings, causes monocytes' progressive death but does not
      affect DCs viability or cell surface phenotype. This resistance of DCs was
      observed both for cells differentiated in vitro from blood monocytes and for a
      population with DCs characteristics already present in blood. This phenomenon
      could affect the local balance of antigen-presenting cells, influence the
      induction and pattern of immune responses developed under the treatment with non
      steroidal anti-inflammatory drugs and, therefore, deserves further investigation.

PMID- 19394593
TI  - Syntactic processing in Korean-English bilingual production: evidence from cross
      linguistic structural priming.
AB  - A structural priming experiment investigated whether grammatical encoding in
      production consists of one or two stages and whether oral bilingual language
      production is shared at the functional or positional level [Bock, J. K., Levelt,
      W. (1994). Language production. Grammatical encoding. In M. A. Gernsbacher (Ed.),
      Handbook of psycholinguistics (pp. 945-984). San Diego, CA: Academic Press] by
      manipulating syntactic structure and argument order in structurally parallel
      Korean and English dative sentences. The results revealed that structural priming
      across languages can occur when both languages share syntactic structure,
      independent of argument order. Specifically, cross-linguistic argument-order
      independent structural priming in canonical Korean postpositional and English
      prepositional dative structures was observed, providing evidence for shared
      bilingual syntactic processing occurring at the abstract, functional level within
      a two-stage grammatical encoding process. This is the first demonstration of
      cross-linguistic priming of argument-order-independent structural information.

PMID- 19394594
TI  - A 9-state hidden Markov model using protein secondary structure information for
      protein fold recognition.
AB  - In protein fold recognition, the main disadvantage of hidden Markov models (HMMs)
      is the employment of large-scale model architectures which require large data
      sets and high computational resources for training. Also, HMMs must consider
      sequential information about secondary structures of proteins, to improve
      prediction performance and reduce model parameters. Therefore, we propose a novel
      method for protein fold recognition based on a hidden Markov model, called a 9
      state HMM. The method can (i) reduce the number of states using secondary
      structure information about proteins for each fold and (ii) recognize protein
      folds more accurately than other HMMs.

PMID- 19394595
TI  - Estimating the mortality effect of the July 2006 California heat wave.
AB  - OBJECTIVE: As a result of the California heat wave in July 2006, county coroners
      reported that the high temperatures during that period caused approximately 147
      deaths. However, heat wave-related deaths are likely to be underreported due to a
      lack of a clear case definition and the multi-factorial nature of heat-related
      mortality. Public health policy suggests a need for a careful assessment of
      mortality following a heat wave. In addition, it is useful to provide a
      comparison of the mortality impact per degree change during heat waves versus
      high temperatures observed during non-heat wave periods. DESIGN: Daily data were
      collected for mortality, weather and ozone in seven California counties impacted
      by the July 2006 heat wave. The association between apparent temperature and
      daily mortality was assessed using a Poisson regression model and combined across
      counties in a meta-analysis. These results were then used to estimate the
      increases in the number of deaths during the heat wave. RESULTS: Our analysis
      indicated that during the July heat wave, there was a 9% (95% CI = 1.6, 16.3)
      increase in daily mortality per 10 degrees Fahrenheit (F) change in apparent
      temperature for all counties combined. This estimate is almost 3 times larger
      than the effect estimated for the full warm season of May-September, during the
      non-heat wave years. Our estimates also determined that actual mortality during
      the July 2006 heat wave was 2-3 times greater than the coroner estimates.
      CONCLUSION: This multi-county analysis provides additional evidence that the
      attributable risk of mortality following a heat wave may be underestimated by
      examining only direct heat-related deaths. In addition, we have found that the
      mortality effect per degrees F is several times higher than that reported during
      non-heat wave periods.

PMID- 19394596
TI  - Live birth after hysteroscopic-guided embryo transfer: a case report.
AB  - OBJECTIVE: To report a case with successful pregnancy using hysteroscopic guided
      embryo transfer (ET). DESIGN: Case report. SETTING: The Farah Hospital (a private
      tertiary referral fertility center). PATIENT(S): A healthy woman with previous
      ICSI trial for male factor infertility underwent a repeat ICSI trial.
      INTERVENTION(S): Embryo transfer was done under hysteroscopic guidance and 3
      embryos were transferred. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S):
      Delivery of a healthy female baby. CONCLUSION(S): Hysteroscopic guided ET is
      feasible and may be of value in cases of difficult transfer.

PMID- 19394597
TI  - Placental polyp with prominent neovascularization.
AB  - Placental polyp is a potentially life-threatening disorder that develops after
      abortion or parturition. Evaluation of neovascularization by multimodal imaging
      is potentially useful in management of placental polyp in a woman who wishes to
      preserve fertility.

PMID- 19394599
TI  - A novel single-cell DNA fingerprinting method successfully distinguishes sibling
      human embryos.
AB  - OBJECTIVE: To validate a novel system for embryonic DNA fingerprinting which can
      reliably distinguish sibling embryos from each other. DESIGN: Prospective,
      randomized, and blinded study. SETTING: Academic center for reproductive
      medicine. PATIENT(S): Blastomeres were obtained from discarded and transferred
      embryos from six patients undergoing IVF treatment. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Single lymphocytes from sibling cell lines and blastomeres
      from sibling day 3 human embryos were evaluated for accurate assignment of
      relationship using whole genome amplification and single-nucleotide polymorphism
      microarrays. RESULT(S): Assignment of single-cell relationships was accomplished
      with 100% accuracy. We also observed complete agreement between the molecular
      karyotype and DNA fingerprint-based identification of embryos implanted in three
      clinical IVF cases after multiple embryo transfer. CONCLUSION(S): These data
      demonstrate the first single-blastomere DNA fingerprinting technology capable of
      unequivocal discrimination of sibling human embryos.

PMID- 19394598
TI  - Levonorgestrel effects on serum androgens, sex hormone-binding globulin levels,
      hair shaft diameter, and sexual function.
AB  - OBJECTIVE: To determine the effects of levonorgestrel (LNG) on serum androgens,
      sex hormone-binding globulin (SHBG), hair shaft diameter, and sexual function in
      women. DESIGN: Substudy of a prospective randomized double-blind study in women
      using an LNG SC implant (LNG-SI), who were treated with doxycycline or placebo.
      SETTING: Medical school department of obstetrics and gynecology. PATIENT(S):
      Forty women were enrolled; 36 completed the study. INTERVENTION(S): Participants
      were randomized to doxycycline 20 mg or an identical placebo orally twice a day
      after LNG-SI insertion. MAIN OUTCOME MEASURE(S): Serum levels of total T (TT),
      free T (FT), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS),
      dihydrotestosterone (DHT), androstanediol glucuronide (AG), SHBG, and LNG; hair
      shaft diameter; and sexual function using the Brief Index of Sexual Function for
      Women and the Arizona Sexual Experiences Scale were assessed. RESULT(S): Serum
      TT, A, DHT, DHEAS, and SHBG declined after LNG-SI insertion. No changes were
      found in FT, AG, hair shaft diameter, or sexual function. Serum LNG correlated
      with SHBG levels. There were no differences between the placebo and doxycycline
      groups. CONCLUSION(S): LNG reduced serum TT, A, DHT, DHEAS, and SHBG but had no
      effect on sexual function or markers of androgen bioactivity.

PMID- 19394600
TI  - Discoid or segmental rectosigmoid resection for deep infiltrating endometriosis:
      a case-control study.
AB  - OBJECTIVE: To evaluate the efficacy of discoid resection for the treatment of
      deep infiltrating endometriosis and whether it could be considered to be a valid
      alternative to the rectosigmoid segmental resection. DESIGN: Case-control study.
      SETTING: Departments of Obstetrics and Gynecology, Ospedale Sacro Cuore of
      Negrar, Verona, and Catholic University of the Sacred Heart, Rome, Italy.
      PATIENT(S): Women with deep infiltrating and intestinal endometriosis divided
      into study group (48 patients) and control group (88 patients). INTERVENTION(S):
      All patients underwent laparoscopic endometriosis excision plus discoid
      rectosigmoid resection (study group) or segmental resection (control group). MAIN
      OUTCOME MEASURE(S): Short- and long-term outcomes. RESULT(S): In the study group,
      median operating time was 200 minutes, with a median estimated blood loss of 203
      mL. Median ileus was 3 days with a median postoperative hospitalization of 7
      days. Early complications were observed in six patients (12.5%), and in two of
      them (4.16%) a surgical management was necessary. Median follow-up period was 33
      months, and five recurrences (10.4%) were registered. In the control group, no
      significant differences were noticed except for longer operative time, more
      temporary ileostomy, postoperative fever, and long-term bladder dysfunctions.
      CONCLUSION(S): Laparoscopic mechanical discoid resection is feasible, markedly
      improved endometriosis related symptoms, and could be considered as a worthy
      alternative to classic segmental resection in selected patients.

PMID- 19394601
TI  - Eutopic endometrial interleukin-18 system mRNA and protein expression at the
      level of endometrial-myometrial interface in adenomyosis patients.
AB  - OBJECTIVE: To investigate the eutopic endometrial interleukin-18 (IL-18) system
      including interleukin-18 (IL-18), IL-18 receptor (IL-18R), and IL-18 binding
      protein (IL-18BP), mRNA, and protein expression in patients with adenomyosis.
      DESIGN: A clinical and molecular study. SETTING: Clinical and academic research
      setting in a university medical center. PATIENT(S): Twenty-eight samples of human
      eutopic endometria were obtained from surgical specimens of normal cycling women
      undergoing hysterectomy for uterine adenomyosis (n = 19); the control group (n =
      9) was women undergoing hysterectomy for benign reason including uterine
      fibroids. INTERVENTION(S): Quantitative competitive polymerase chain reaction (QC
      PCR) and immunohistochemistry studies were performed. MAIN OUTCOME
      MEASUREMENT(S): The differences of the IL-18 system mRNA and the ratio of IL-18BP
      to IL-18 in the eutopic endometrium of uterine adenomyosis and control group were
      analyzed. RESULT(S): IL-18 system mRNA and protein expression was demonstrated in
      the eutopic endometrium of both adenomyosis and control women. Quantitative
      competitive PCR demonstrated that endometrial IL-18R mRNA and the ratio of IL
      18BP to IL-18 were significantly increased in adenomyosis patients in comparison
      to the control group. Pearson's correlation showed a significant correlation
      between IL-18 and IL-18R in the eutopic endometrium of women with uterine
      adenomyosis, but not the control group. CONCLUSION(S): The expression of the
      eutopic endometrial IL-18 system and the ratio of antagonist to agonist at the
      level of the endometrial-myometrial interface (EMI) may possibly be responsible
      for the pathologic process of adenomyosis.

PMID- 19394602
TI  - How to predict implantation? No correlation between embryonic aneuploidy and
      soluble human leukocyte antigen G-concentrations.
AB  - OBJECTIVE: To determine if soluble human leukocyte antigen-G (sHLA-G)
      concentrations in spent culture media may assist in identifying the normal embryo
      for implantation. DESIGN: Prospective blinded comparative study. SETTING:
      Reproductive genetic and reproductive medicine centers. PATIENT(S): One hundred
      and sixteen embryos obtained from eight patients undergoing in vitro
      fertilization (IVF) with preimplantation genetic diagnosis (PGD).
      INTERVENTION(S): Culture media obtained 2 days after fertilization were analyzed
      for sHLA-G concentrations using an enzyme-linked immunosorbent assay (ELISA)
      assay. A sHLA-G concentration of >or=1.9 mIU/mL was considered a positive
      predictor for successful implantation. Polar bodies and blastomeres from day-3
      embryos were tested by PGD for 5 to 11 chromosomes: 8, 9, 13, 15, 16, 17, 18, 21,
      22, X, and Y. MAIN OUTCOME MEASURE(S): The results of the sHLA-G concentrations
      were compared with the results of the PGD analyses. RESULT(S): We found an sHLA-G
      concentration >or=1.9 mIU/mL in 48% (56 out of 116) and normal PGD results in 52%
      (57 out of 116) of embryos. Of the embryos with normal PGD results, 46% (26 out
      of 57) had sHLA-G concentrations >or=1.9 mIU/mL. Among the embryos with sHLA-G
      >or=1.9 mIU/mL, 46% (26 out of 56) had normal PGD results, and 21% of embryos
      displayed both normal PGD results and sHLA-G >or=1.9 mIU/mL. CONCLUSION(S): No
      correlation between concentrations of sHLA-G in embryo culture media and PGD
      results of an embryo's aneuploidy were observed.

PMID- 19394603
TI  - A prospective, randomized, double-blind, placebo-controlled trial of multimodal
      intraoperative analgesia for laparoscopic excision of endometriosis.
AB  - OBJECTIVE: To assess the efficacy of multimodal intraoperative analgesia in
      reducing postoperative pain and/or opioid requirements in women undergoing
      laparoscopic excision of endometriosis. DESIGN: Prospective, randomized, double
      blind, placebo-controlled trial. SETTING: Endogynecologic department of a
      university teaching hospital. PATIENT(S): Women booked for laparoscopic excision
      of endometriosis. INTERVENTION(S): Intraoperative multimodal analgesia versus
      placebo. Analgesia consisted of Diclofenac sodium 100 mg suppository per rectum
      and 0.75% Ropivacaine to portal sites, subperitoneally under excision sites and
      topically to each subdiaphragmatic area. MAIN OUTCOME MEASURE(S): Postoperative
      total hospital opioid analgesic requirements and postoperative pain intensity.
      RESULT(S): The study was terminated prematurely, after a planned interim analysis
      (which included 66 randomized patients or 43% of the planned number of patients)
      found significantly less total hospital opioid requirements in the analgesic
      group compared with the placebo group (19.0 mg vs. 34.5 mg; difference -14.0 mg
      [95% confidence interval -26.0 to -2.0 mg]). There was no difference in
      postoperative pain intensity between the two groups. CONCLUSION(S): The use of
      multimodal intraoperative analgesia at laparoscopic excision of endometriosis
      reduces postoperative opioid requirements.

PMID- 19394604
TI  - Cigarette smoking affects specific sperm oxidative defenses but does not cause
      oxidative DNA damage in infertile men.
AB  - OBJECTIVE: To evaluate the effects of tobacco consumption on the oxidative
      defenses of sperm, the glutathione system (GS), and sperm DNA oxidation. DESIGN:
      Double-blind experimental study. SETTING: Andrology laboratory in a university
      affiliated private setting. PATIENT(S): One hundred seventeen semen samples from
      infertile males. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): (a) sperm GS
      enzymatic activity with respect to glutathione peroxidase isoforms GPx-1 and GPx
      4, glutathione reductase (GR), and cellular glutathione (GSH) content (n = 29);
      (b) GPx-1, GPx-4, and GR mRNA expression analysis (n = 33); (c) oxidative DNA
      damage quantification using OXIDNA assay kit (n = 55). Two groups were
      established: nonsmoking and smoking males. The t tests were employed to detect
      significant differences between groups. RESULT(S): We identified a significant
      decrease in sperm GPx-4 activity but not in GPx-1 and GSH activity in smokers
      compared with nonsmokers. A significant decrease was also observed in GPx-1, GPx
      4, and GR mRNA expression in the former group. Interestingly, we did not observe
      any significant variation in the percentage of cells with oxidative damage of the
      DNA or in the average level of oxidation of affected cells with respect to the
      smoking condition of the male. CONCLUSION(S): We demonstrate that smoking has a
      negative impact on intracellular antioxidant enzymes but that effect does not
      increase oxidative DNA damage. Thus, the effects of reduced oxidative defenses in
      sperm as a result of cigarette smoking are yet to be elucidated.

PMID- 19394605
TI  - Poor success of gonadotropin-induced controlled ovarian hyperstimulation and
      intrauterine insemination for older women.
AB  - OBJECTIVE: To determine the success rates and utility of controlled ovarian
      hyperstimulation in conjunction with intrauterine insemination (COH/IUI) cycles
      in women aged 38-39 years versus women >or=40 years old. DESIGN: Retrospective
      cohort study. SETTING: Tertiary-care academic medical center. PATIENT(S): There
      were 130 women, 57 aged 38-39 years (42.6%) and 73 aged >or=40 years (57.4%), who
      underwent 262 IUI cycles (range 1-3 cycles per woman). INTERVENTION(S):
      Infertility treatments with gonadotropins and IUI. MAIN OUTCOME MEASURE(S):
      Clinical pregnancy rates and live birth rates stratified by age. RESULT(S): The
      most common infertility diagnosis was diminished ovarian reserve, which was found
      more frequently among women aged >or=40 years than among the slightly younger
      group. The age-specific groups were similar in their baseline characteristics and
      cycle parameters. Women who were 38-39 years old had an overall live birth rate
      of 6.1% per cycle, with no live births occurring after the second cycle, and
      women >or=40 years old had an overall live birth rate of 2.0% per cycle, with all
      births occurring in the first cycle. CONCLUSION(S): The efficacy of COH/IUI
      cycles significantly decreases with age, but women aged 38-39 years had
      reasonable success during the first two cycles. However, for women aged >or=40
      years, no benefit after a single cycle of COH/IUI was observed. Women aged >or=40
      years should be considered for in vitro fertilization after one failed COH/IUI
      cycle.

PMID- 19394607
TI  - Autoamputated adnexa presents as a peritoneal loose body.
AB  - We report a case of unilateral adnexal absence with a peritoneal loose body.
      Laparoscopic findings and medical history suggested that she had adnexal torsion
      in her childhood followed by its calcification and autoamputation.

PMID- 19394606
TI  - Changes in histone methylation during human oocyte maturation and IVF- or ICSI
      derived embryo development.
AB  - OBJECTIVE: To characterize the histone methylation pattern during human oocyte
      maturation and embryo development after conventional IVF and ICSI. DESIGN:
      Experimental study. SETTING: Reproductive center of hospital. PATIENT(S): Women
      underwent IVF or ICSI. INTERVENTION(S): Immature and mature oocytes were
      collected from patients undergoing ICSI. Tripronuclear and normally fertilized
      embryos were obtained from patients undergoing IVF or ICSI. MAIN OUTCOME
      MEASURE(S): The distribution patterns of dimethylated histone H3 lysine 9 (H3K9)
      and histone H4 arginine 3 (H4R3) in oocytes and embryos were observed by indirect
      immunofluorescent staining and scanning confocal microscopy. RESULT(S): H3K9 and
      H4R3 were dimethylated throughout the meiotic maturation of human oocytes and the
      tripronuclear embryo development from two-cell to blastocyst stage. However, at
      the pronuclear stage, approximately half of the tripronuclear IVF zygotes
      displayed strong staining of MeH3K9 in one pronucleus, whereas MeH4R3 staining
      was always uniform in all three pronuclei. In the other half of the tripronuclear
      zygotes, all three pronuclei were strongly stained with MeH3K9 in some cases, and
      the remaining zygotes were completely unstained. Moreover, with progressively
      increasing fragmentation of blastomeres in ICSI-derived 2PN embryos with low
      morphological grade, H3K9 dimethylation decreased when compared with that of IVF
      embryos. CONCLUSION(S): Asymmetric distribution of the dimethylation form of H3K9
      exists in human zygote pronuclei. The ICSI-derived embryos with low morphological
      grade are more likely to display H3K9 demethylation than their IVF counterparts.

PMID- 19394608
TI  - Tumor necrosis factor alpha -C850T polymorphism is significantly associated with
      endometriosis in Asian Indian women.
AB  - OBJECTIVE: To establish the association of tumor necrosis factor alpha (TNFA)
      promoter C850T polymorphism in Asian Indian women with endometriosis. DESIGN:
      Case control study, from multiple gynecological centers from Hyderabad, a
      cosmopolitan city in southern India. The study included 245 women who comprised
      110 surgically confirmed cases of endometriosis, 50 ultrasonographically
      confirmed cases of fibroid tumors, and 85 healthy female volunteers. SETTING:
      Academic hospital. PATIENT(S): The cases were 245 women, 160 patients and 85
      controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Tumor necrosis factor
      alpha -C850T polymorphism may be used as a molecular marker for endometriosis in
      our population. RESULT(S): In this study we have demonstrated an association
      between TNFA -C850T polymorphism and endometriosis. The T allele is significantly
      associated with endometriosis when compared to women with fibroids as well as
      healthy controls. Our data imply that the T allele is associated with
      endometriosis (OR = 1.9594: 95% CI, 1.3833-2.7753; in our population. The TT
      genotype increases the risk of endometriosis by fourfold (4.5542: 95% CI, 2.0388
      10.1701. CONCLUSION(S): This study suggests that -C850T TNFA gene polymorphism
      could be used as a relevant molecular marker to identify women with risk of
      developing endometriosis in our population.

PMID- 19394609
TI  - Attenuation of ischemia-reperfusion injury with Marrubium cordatum treatment in
      ovarian torsion-detorsion model in rabbits.
AB  - OBJECTIVE: To investigate protective effects of Marrubium cordatum extract on
      ovary torsion-detorsion. DESIGN: Controlled research study. SETTING: Marrubium
      cordatum extract was obtained by methanol extraction. ANIMAL(S): Six-month-old
      female New Zealand rabbits. INTERVENTION(S): In the first phase, antioxidant
      activity of M. cordatum extract was evaluated. In the second phase, M. cordatum
      extract at doses of 0, 250, 500, and 1,000 mg/kg was studied for dose
      determination. In the third phase, the protective role of M. cordatum on ovarian
      torsion-detorsion injury was evaluated in sham control, torsion-detorsion,
      torsion-detorsion +M. cordatum (1,000 mg/kg). MAIN OUTCOME MEASURE(S): 1,1
      Diphenyl-2-picrylhydrazyl, nitric oxide radical scavenging activity, reducing
      power capacity, and total phenolic compounds were assayed. Glutathione,
      malondialdehyde, catalase, and glutathione peroxidase were measured.
      Histopathological examination was also conducted. RESULT(S): Marrubium cordatum
      significantly inhibited 1,1-diphenyl-2-picrylhydrazyl, nitric oxide radicals, and
      showed a powerful reducing activity. Marrubium cordatum did not adversely affect
      biochemical and histopathological parameters at all doses. Malondialdehyde level
      and catalase activity in the torsion-detorsion group were significantly increased
      compared with those of the sham group, whereas the glutathione level and
      glutathione peroxidase activity were significantly decreased compared with those
      of the sham group. Marrubium cordatum treatment significantly lowered the
      malondialdehyde level and catalase activity but increased the glutathione level
      in torsion-detorsion injury. Histopathologically, severe congestion, hemorrhage,
      edema, and leukocyte infiltration were observed in the torsion-detorsion group.
      Marrubium cordatum treatment ameliorated these alterations. CONCLUSION(S):
      Marrubium cordatum attenuates ischemia-reperfusion-induced biochemical and
      histopathological alterations.

PMID- 19394610
TI  - Impact of fatness, insulin, and gynecological age on luteinizing hormone
      secretory dynamics in adolescent females.
AB  - OBJECTIVE: To study the link between fatness and gonadotropin secretion.
      Overweight status is linked to polycystic ovary syndrome (PCOS) in adolescents.
      We postulated that heavier adolescents without symptoms would secrete LH with:
      [1] increased pulse frequency (LHPF) and [2] exaggerated integrated
      concentrations (LHAUC). DESIGN: Cross-sectional. SETTING: General clinical
      research center. PATIENT(S): Eighty-seven postmenarcheal cyclic adolescents from
      lean to overweight recruited during the follicular phase. INTERVENTION(S):
      Luteinizing hormone sampling: [1] every 10 minutes/24 hours; [2] at 20-minute
      intervals after a GnRH challenge. MAIN OUTCOME MEASURE(S): The LHPF and LHAUC
      (calculated by the CLUSTER algorithm). Hormonal and metabolic covariates included
      percent body fat (PercentBF), insulin-like growth factor-I (IGF-I), fasting
      insulin, and the insulin resistance index HOMA-IR. The SAS software was used for
      analyses. RESULT(S): The PercentBF and younger gynecological age predicted faster
      LHPF. Fatness was negatively linked to LHAUC, which was best predicted by
      PercentBF and IGF-1 in multivariate modeling (R(2) = 0.25). The PercentBF and
      insulin predicted a lower 20-minute LH response to GnRH. CONCLUSION(S): [1]
      Higher adiposity and younger gynecological age predict rapid LHPF. [2] The early
      years after menarche represent a vulnerable window for an exaggerated LHPF with
      weight gain. [3] In healthy adolescents, higher adiposity is linked to lower
      LHAUC, thereby preserving pituitary stores.

PMID- 19394611
TI  - A new modular nail for the diaphyseal fractures of the humerus.
AB  - Over a period of 5 years, 63 traumatic and eight pathological diaphyseal humeral
      fractures were treated with a new modular humeral nail. The nail is cannulated,
      square in shape--with concave sides--and has two different extensions that can be
      used with either the antegrade or the retrograde approach. Adequate rotational
      and axial stability is provided without the need for distal locking screws in the
      majority of fractures, while the need for proximal locking screws during the
      antegrade procedure is abolished. This study aims to present the 'Garnavos' nail
      and the results of its use, along with proposals and guidelines that should be
      considered whenever intramedullary nailing is selected for the treatment of
      diaphyseal humeral fractures.

PMID- 19394612
TI  - Pregnancy and HIV-positive patients. FIGO Committee for the Ethical Aspects of
      Human Reproduction and Women's Health.

PMID- 19394613
TI  - Professional obligations related to developments in genomics and proteomics in
      human testing. FIGO Committee for the Ethical Aspects of Human Reproduction and
      Women's Health.

PMID- 19394614
TI  - Compared effects of surgical and natural menopause on climacteric symptoms,
      osteoporosis, and metabolic syndrome.
AB  - OBJECTIVE: To compare the effects of surgical (ie, earlier) and natural (ie,
      later) menopause on climacteric symptoms, osteoporosis, and metabolic syndrome.
      METHOD: The study was conducted with 94 women who underwent hysterectomy and
      bilateral oophorectomy and 95 women who were older than 40 years and in natural
      menopause. None had received hormone therapy or osteoporosis treatment. Metabolic
      syndrome was defined according to the National Cholesterol Education Program
      Adult Treatment Panel III. RESULTS: The rates of hot flushes (P=0.001), sweating
      (P=0.001), poor memory (P=0.04), change in sexual desire (P=0.04), and
      osteoporosis (diagnosed in the hip bone, P=0.005) were significantly higher among
      the women in surgical menopause, but the rate of metabolic syndrome was similar
      in the 2 groups (47.8% and 40%; P=0.28). CONCLUSION: Compared with natural
      menopause, surgical menopause was found to be associated with higher rates of
      climacteric symptoms and osteoporosis but not of metabolic syndrome.

PMID- 19394615
TI  - Adolescent and youth reproductive health care and confidentiality FIGO Committee
      for the Ethical Aspects of Human Reproduction and Women's Health.

PMID- 19394616
TI  - Smoking induces lipoprotein-associated phospholipase A2 in cardiovascular disease
      free adults: the ATTICA Study.
AB  - OBJECTIVES: We studied the association of lipoprotein-associated phospholipase
      A(2) (Lp-PLA(2)) mass and activity with various lifestyle, clinical and
      biochemical characteristics in cardiovascular disease (CVD) free adults.
      BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a novel
      biomarker of inflammation and risk for CVD. The Lp-PLA(2) mass and activity are
      primarily influenced by the plasma levels of low-density lipoprotein (LDL),
      however the influence of various lifestyle characteristics on Lp-PLA(2) have not
      been adequately studied. METHODS AND RESULTS: In a random sub-sample of 186
      subjects, 64 men (52+/-13 years) and 122 women (48+/-13 years) from the ATTICA
      Study (Greece), Lp-PLA(2) activity and mass in total plasma as well as the enzyme
      activity and mass associated with high-density lipoprotein (HDL-Lp-PLA(2)) were
      determined using established methods. Several socio-demographic, lifestyle,
      clinical and biochemical parameters were assessed in all participants. Multiple
      linear regression analysis revealed that among the lifestyle characteristics,
      total plasma Lp-PLA(2) activity and mass were positively and independently
      associated with current smoking (p=0.02 and p=0.05, respectively), as well as
      with exposure to second-hand smoke (p=0.02 and p=0.01, respectively).
      Furthermore, HDL-Lp-PLA(2) activity and mass were inversely and independently
      associated with current smoking (p=0.04 and p=0.09, respectively). CONCLUSIONS:
      Smoking is associated with and might even induce an increase in proatherogenic
      total plasma Lp-PLA(2), but attenuates antiatherogenic HDL-Lp-PLA(2). These
      results further support the role of smoking as an important avoidable cause of
      CVD.

PMID- 19394617
TI  - Structural and electrophysiological changes in atherosclerotic radial artery
      grafts account for impairment of vessel reactivity.
AB  - To evaluate the potential impact of using atherosclerotic radial artery (RA)
      conduits as grafts in coronary artery bypass surgery, we examined the
      vasoconstrictor and electrophysiological properties of mildly and severely
      atherosclerotic RAs. Vasoconstrictor responses were measured in cannulated and
      pressurized (85mmHg) RA segments and K(+) currents were measured in single smooth
      muscle cells. In the cannulated and pressurized vessel preparation, the pressure
      induced dilation was attenuated in both the mildly and severely atherosclerotic
      RAs when compared to normal samples. Contractile responses to potassium chloride,
      thromboxane A(2) (TXA(2)) analog U-46619 and to E-ring and F-ring isoprostanes
      were also attenuated. Smooth muscle cells (SMCs) from atherosclerotic arteries
      manifested significantly greater K(+) current density (76.6+/-22.4pA/pF) when
      compared to normal SMCs (18.6+/-3.3pA/pF). Our results show that vasocontractile
      properties of both mildly and severely atherosclerotic arteries are reduced when
      compared to normal RAs. A possible explanation for this could be decreased
      vascular compliance due to arterial stiffening and a substantial augmentation of
      K(+) currents in sclerotic smooth muscle cells. We conclude that caution should
      be exercised when using RA grafts with atherosclerotic lesions since they could
      significantly impact the clinical outcome of CABG surgery.

PMID- 19394618
TI  - Endogenous tissue plasminogen activator and risk of recurrent cardiac events
      after an acute coronary syndrome in the MIRACL study.
AB  - OBJECTIVE: To examine the relationship of baseline tissue plasminogen activator
      (t-PA) to early cardiovascular risk after an acute coronary syndrome, and the
      effect of intensive statin therapy. METHODS: We measured plasma t-PA in 2860 of
      the 3086 (93%) subjects in the MIRACL study, an international randomized trial of
      atorvastatin 80mg daily versus placebo in patients with acute coronary syndromes.
      The relationship of t-PA to death, non-fatal acute myocardial infarction, cardiac
      arrest, or worsening angina over 16 weeks was assessed by Cox Proportional
      Hazards. D-dimer was measured in a random sample of 395 subjects. RESULTS: Higher
      baseline t-PA was significantly related to the risk of recurrent events (HR=1.25,
      p=0.0014). This relationship was unaffected by adjustment for age, sex, troponin,
      hsCRP, and lipids (HR=1.17, p=0.029), but was attenuated by adjustment including
      body mass index and smoking (HR=1.14, p=0.08). D-dimer and t-PA concentrations
      were not related. Atorvastatin reduced the risk of recurrent events, but did not
      affect t-PA or D-dimer concentrations or the relationship of t-PA to outcomes.
      CONCLUSION: In patients with acute coronary syndromes, increasing t-PA
      concentration was related to a higher early risk of recurrent events,
      paradoxically reflecting impaired endogenous fibrinolysis. This relationship is
      due in part to the association of t-PA with age, body mass index and smoking.
      Although statins lower the risk of recurrent events after acute coronary
      syndromes, it is unlikely that this benefit is achieved through thrombolytic and
      fibrinolytic pathways.

PMID- 19394620
TI  - Effects of surface wettability and roughness of microchannel on flow behaviors of
      thermo-responsive microspheres therein during the phase transition.
AB  - The flow characteristics of monodisperse thermo-responsive poly(N
      isopropylacrylamide) (PNIPAM) microspheres during the phase transition in
      microchannels with different surface wettabilities and roughnesses are
      investigated systematically. Glass microchannels are modified by hydroxylation
      treatment to achieve hydrophilic surface, by self-assembly of
      chlorotrimethylsilane to realize hydrophobic surface, and by coating with silica
      nanoparticles to generate rough surface. The phase transition of PNIPAM
      microspheres in microchannels is induced by local heating. The results show that
      the surface wettability and roughness of microchannel significantly affect the
      flow behaviors of PNIPAM microspheres during the phase transition. It is much
      easier for the PNIPAM microspheres in microchannel with hydrophobic surface to
      stop right after the phase transition than those in microchannel with hydrophilic
      surface, and it is also much easier for the PNIPAM microspheres in microchannel
      with rough surface to stop right after the phase transition than those in
      microchannel with smooth surface. These results indicate that hydrophobic and
      rough surface properties of the microchannel can enhance the site-specific
      targeting of PNIPAM microspheres caused by the phase transition. The results in
      this study provide valuable information for the application of thermo-responsive
      drug carriers in site-specific targeting therapy.

PMID- 19394619
TI  - Sodium octanoate to reverse indoxyl sulfate and p-cresyl sulfate albumin binding
      in uremic and normal serum during sample preparation followed by fluorescence
      liquid chromatography.
AB  - Indoxyl sulfate and p-cresyl sulfate are protein-bound marker molecules in
      chronic kidney disease. Recent findings suggest that indoxyl sulfate and p-cresyl
      sulfate directly contribute to the uremic syndrome. A method for quantification
      of p-cresyl sulfate and indoxyl sulfate total serum concentrations was developed.
      We used sodium octanoate as competitor to replace non-covalent binding of p
      cresyl sulfate and indoxyl sulfate to albumin. Total, within-run, between-run and
      between-day imprecision for indoxyl sulfate and p-cresyl sulfate were all below
      6%. The limit of quantification was 3.2microM for both analytes. Recovery, tested
      in hemodialysis patients, was 102% for indoxyl sulfate and 105% for p-cresyl
      sulfate. Deming regression demonstrated good agreement for indoxyl sulfate
      between this new method and an external HPLC method. Method comparison for p
      cresyl sulfate of the new method with our in-house GC-MS method demonstrated good
      agreement, whereas method comparison with an external HPLC method revealed a
      small proportional bias. Sodium octanoate binding competition is a novel sample
      preparation that allows for direct quantification of indoxyl sulfate and p-cresyl
      sulfate.

PMID- 19394621
TI  - Mixed anionic and zwitterionic surfactant based microemulsions as vehicles for
      solubilizing organodiselenides.
AB  - Spectral and physiochemical behavior of water/sodium bis-(2
      ethylhexyl)sulfosuccinate (AOT)/isooctane (ME-I) and water/AOT+lecithin
      (LC)/isooctane (ME-II) microemulsions has been investigated in the presence of
      organodiselenides. It was found that the OH, CO and C-O-C FTIR stretching
      frequency of the formulated microemulsions change with the addition of
      organodiselenides. Interaction with Acridine Orange (AO) indicates
      organodiselenide presence at the interface. Estimates of the micropolarities of
      the microemulsions at different water contents were carried out in terms of an
      empirical polarity parameter E(T)(30). The values increase with the increase in
      omega = [H(2)O]/[surfactant]. The emission spectra of AO reveal the quenching
      capacities of the added organodiselenides. The temperature induced percolation
      process has also been studied. The results indicate a subsequent increase in
      solubilization of organodiselenide in ME-II as compared to ME-I.

PMID- 19394622
TI  - Surface complexation modeling of dual-mode adsorption of organic acids: phthalic
      acid adsorption onto hematite.
AB  - Recent spectroscopic and theoretical investigations provide evidence suggesting
      organic acids bind to mineral surfaces simultaneously as inner- and outer-sphere
      complexes and that the relative importance of these species varies with solution
      chemistry (e.g., pH), mineral type, and organic acid. Constraining surface
      complexation models (SCMs) with this information has proven difficult; however,
      as efforts to tune the surface complex stoichiometry within the SCM to match the
      structures and speciation trends observed in the spectra are seldom successful.
      In this study, the adsorption of phthalic acid on hematite was investigated using
      the Extended Constant Capacitance Model (ECCM) in a manner that was consistent
      with reported spectroscopic results. The influence of adjustable model parameters
      (capacitance, site density, and charge distribution) on model fit and the
      corresponding determination of surface speciation was tested. Although nearly
      equivalent fits were determined with a model comprised of a single outer-sphere
      complex and a dual-mode model that included one inner-sphere complex and one
      outer-sphere complex, results with the dual-mode model were more consistent with
      spectroscopic results from the literature. The surface speciation predicted by
      the dual-mode model was dependent on model parameter choice, with the
      concentration of the inner-sphere complex at low pH significantly increasing with
      decreasing inner-layer capacitance and site density. These results suggest to
      reliably use SCMs to describe adsorption over a wide range of experimental
      conditions requires direct knowledge of surface speciation to constrain the
      selection of surface complexation reactions and adjustable model parameters.

PMID- 19394623
TI  - Effect of molecular weight of triglycerides on the formation and rheological
      behavior of cubic and hexagonal phase based gel emulsions.
AB  - The effect of triglyceride molecular weight on the formation and rheology of
      cubic (O/I(1)) and hexagonal (O/H(1)) phase based gel emulsions has been studied
      in water/C(12)EO(8) systems. It was found that the addition of TDG (1,2,3
      tridecanoyl glycerol) in the micellar solution leads to the formation of the I(1)
      phase, which can solubilize some added oil. From SAXS data, it is revealed that
      the interlayer spacing (d) and the length of hydrophobic part (r(I)) increase
      with increasing TDG concentration in the I(1) phase, whereas the effective cross
      sectional area (a(s)) decreases. After the oil solubilization limit, the d value
      remains nearly constant, indicating the I(1)+O phase appears. The high viscosity
      of the I(1) phase facilitates the formation of the O/I(1) gel emulsion. It has
      been observed that the formation and stability of the O/I(1) and O/H(1) gel
      emulsion is highly dependent on the molecular weight of triglycerides, namely,
      the high molecular weight triglycerides show better performance (formation and
      stability) compared to the low molecular weight triglycerides. The rheological
      behavior of the I(1) phase was found to change from viscoelastic to elastic
      nature with TDG content. The values of the complex viscosity, mid absolute
      value(eta*) show different trends at different fixed frequencies within the I(1)
      phase, whereas it decrease monotonically in the O/I(1) gel emulsions. The
      increasing values of the absolute value(eta*) (at lower frequency) could be due
      to the neighboring micellar interaction and decreasing values of the absolute
      value(eta*) in the O/I(1) gel emulsion could relate to the volume fraction of the
      I(1) phase in the system. It is also figured out that the rheological parameters
      (elastic modulus, viscous modulus, and absolute value(eta*)) of the O/I(1) the
      gel emulsion do not depend on the oil nature, whereas the O/H(1) gel emulsion
      shows oil nature dependency.

PMID- 19394624
TI  - Effect of disjoining pressure on the drainage and relaxation dynamics of liquid
      films with mobile interfaces.
AB  - This work presents a generalized lubrication approximation of the drainage and
      relaxation of thin liquid films with tangentially mobile surfaces. The proposed
      model accounts for the dynamic effects and the role of surface forces of
      intermolecular origin. The van der Waals and hydrophobic attractive and the
      electrostatic and steric repulsive components of the disjoining pressure are
      included in the numerical calculations of the dynamics and relaxation of one
      dimensional films. Different regimes of film drainage are discussed: regular and
      unstable mechanisms of thinning depending on the magnitude of the Reynolds
      number; pimple formation in the presence of large enough attractive surface
      forces; and stabilizing effects of the disjoining pressure repulsive components.
      In the case of relaxation, it is proven that the disturbances in the film
      thickness: decrease exponentially to the equilibrium state without taking into
      account the role of the disjoining pressure; increase very fast to the point of
      film rupture in the presence of attractive surface forces; oscillate with
      exponentially decreasing amplitudes towards the state of stable equilibrium when
      the electrostatic and steric repulsive forces are significant.

PMID- 19394625
TI  - A humic-acid-like polycondensate produced with no use of catalyst.
AB  - The synthesis and physicochemical characterization of a water soluble humic-acid
      like polycondensate (HALP), which mimics fundamental physicochemical and
      spectroscopic properties of natural humic acids is presented. The polymer can be
      synthesized under ambient O(2) by oxidative co-polymerization of gallic (GA) and
      protocatechuic (PA) acid at pH >9, with no need for a catalyst. Solid state (13)C
      NMR spectra for GA-PA-HALP show that ring-opening reactions of GA, PA monomers
      are involved in GA-PA-HALP formation. EPR spectroscopy shows that GA-PA-HALP
      contains stable phenol-based radicals, with pH-dependent concentration. The H
      binding profile of GA-PA-HALP follows the NICA-Donnan model, with two sets of
      distributed pK(a) values in the range 4-6 corresponding to carboxyl groups, and 7
      9 corresponding to phenolic groups, as in natural HA. GA-PA-HALP bears a
      permanent negative charge Q(0)=-2.3 equiv kg(-1) which is higher than the
      literature Q(0) values of -1 to -2 equiv kg(-1) observed for natural HAs. A
      critical comparison of the present data with literature data is provided.

PMID- 19394626
TI  - Microfluidic preparation of monodisperse ethyl cellulose hollow microcapsules
      with non-toxic solvent.
AB  - Monodisperse ethyl cellulose (EC) hollow microcapsules are successfully prepared
      by using a simple and novel method which combines microfluidic double
      emulsification and solvent diffusion. To dissolve EC, we use a non-toxic solvent
      ethyl acetate (EA), instead of methylene chloride which is commonly used but
      carcinogenic. By introducing chitosan (CS) into outer fluid, we can increase the
      viscosity of outer fluid and obtain smaller microcapsules which are desired. On
      the other hand, introducing CS only into outer fluid could lead to osmotic
      pressure gradient between the inner and outer fluids which could cause the
      undesired collapse of microcapsules. To avoid the collapse phenomena, we try
      adding iso-osmotic NaCl into inner aqueous fluid but failed in achieving osmotic
      pressure balance possibly because the small Na(+) and Cl(-) ions could penetrate
      the EC matrix during solidification. However, success is achieved when we
      introduce CS into both inner and outer fluids because CS polymer is too big to
      permeate through the EC matrix and thus could maintain iso-osmotic state. The
      microcapsules prepared under iso-osmotic state show perfect spherical shape and
      no collapse. The method developed in this work provides a novel and versatile
      route for fabricating monodisperse biocompatible microcapsules composed of water
      insoluble polymers.

PMID- 19394627
TI  - Adsorption properties of oligo(fluorooxetane)-b-poly(ethylene oxide)-b
      oligo(fluorooxetane) triblock copolymers at the air-water interface: comparison
      of hydroxyl and acetate end groups.
AB  - ABA triblock copolymers, where A is an oligo(fluorooxetane) and B is
      poly(ethylene oxide) (PEO), are prepared easily using an alpha,omega-dihydroxy
      PEO initiator and cationic, ring-opening polymerization of a fluorinated oxetane
      monomer. Terminal hydroxyl groups can be converted readily and quantitatively to
      acetate groups using acetic anhydride. Both types of triblock copolymers are
      surface active in water. The hydroxyl- and acetate-terminated triblocks exhibit
      differences in adsorption behavior. Both materials show similar surface tension
      reduction efficiencies (minimum surface tension at aggregation limit); however,
      the acetate-terminated triblock copolymer is much more effective (surface tension
      reduction at a given concentration to the aggregation limit). This behavior is
      explained by the influence of hydrogen bonding on adsorption properties of the
      hydroxyl-terminated triblock copolymer compared to the acetate-terminated
      version.

PMID- 19394628
TI  - Gelatin induced reduction of uniform nano-platelets of Ni(OH)2 to Ni metal.
AB  - Uniform stable nanosize nickel platelets were prepared by first coating Ni(OH)2
      particles of the same shape with gelatin and then heating them at moderate
      temperatures in nitrogen without addition of any reducing agents. The resulting
      platelets consist of a mixture of Ni and NiO. Depending on the amount of gelatin
      coating and temperature, up to 73% of solids were converted to the metal.
      Subsequent heating of such powders at 190 degrees C in a stream of 5% H2 in N2
      produced only Ni platelets with a modal length of approximately 60 nm and several
      nm thick.

PMID- 19394629
TI  - Effect of the adsorption of oxygen on electronic structures and geometrical
      parameters of armchair single-wall carbon nanotubes: a density functional study.
AB  - We investigated the effect of atomic and molecular oxygen adsorption on the
      geometries and electronic properties of small and large armchair single-walled
      carbon nanotubes (SWCNTs) by means of the density functional theory (DFT). We
      calculated the equilibrium geometries, energetics, and electronic properties of
      the nanotubes as well as the tube-molecules. Global indices such as electronic
      chemical potential and hardness were calculated using the Kopmann's theorem. Our
      investigation involved the physisorption of molecular oxygen, chemisorption of
      atomic oxygen, and formation of epoxide-like structures. The adsorption energies
      of the oxygen molecules physisorbed to different sites were determined by
      calculating the short-range interactions. The effect of the tube diameter on the
      stability of the tube-O(2) system was studied for the different sites. Also we
      considered the orientation of O(2) molecule during adsorption of O(2) molecule on
      the outer surface of tubes. Adsorption of oxygen atom on top of the carbon atom
      of the tubes was also considered. We found out that O atoms bind to the outer
      surface of the SWCNTs to give stable epoxide-like structures. The most stable
      epoxide-like structure on the outer surface of the nanotubes was the (4,4)-O
      system with a calculated adsorption energy of -2.944 eV.

PMID- 19394630
TI  - Synthesis of mesoporous silica-pillared clay by intragallery ammonia-catalyzed
      hydrolysis of tetraethoxysilane using quaternary ammonium surfactants as gallery
      templates.
AB  - Mesoporous silica-pillared montmorillonite (MMT) materials were synthesized by
      intragallery ammonia-catalyzed hydrolysis tetraethoxysilane (TEOS). The reaction
      involved hydrolysis and condensation of tetraethoxysilane in the presence of
      intragallery surfactants templates. Powder X-ray diffraction (XRD), N(2)
      adsorption-desorption isotherms, scanning electron microscopy (SEM) and Fourier
      transform infra-red (FT-IR) spectra were employed to characterize the mesoporous
      silica-pillared montmorillonite. These novel materials exhibited reflections
      corresponding to a basal spacing of 4.76-5.62 nm, a uniform pore size of 3.75
      4.51 nm and large surface areas of 597.2-712.4 m(2)/g. And the porous structure
      and physical properties of silica-pillared montmorillonite derivatives remained
      stable after heating for 5 h at 700 degrees C in air. Our results indicate that
      surfactants play a decisive role in pore formation, because they act as micelle
      like template during the hydrolysis of TEOS. These mesoporous silica-pillared
      montmorillonite materials exhibit excellent catalytic activity and selectivity
      for coker gas oil cracking reaction in comparison to normal MCM-41 and Al-MCM-41.

PMID- 19394631
TI  - Cloud point extraction and flame atomic absorption spectrometry determination of
      trace amounts of copper(II) ions in water samples.
AB  - Cloud point extraction was used with lipophilic Schiff base N,N'-bis(2
      hydroxyacetophenone)-1,2-propanediimine (L) as a pre-concentration step prior to
      flame atomic absorption spectrometry determination of trace amounts of copper in
      water samples. The process is based upon the formation of Cu(II)/L complexes
      soluble in a micellar phase composed by the non-ionic surfactant Triton X-114.
      These complexes are then extracted into the surfactant-rich phase, at above its
      cloud point temperature. The parameters affecting the extraction efficiency, i.e.
      pH of aqueous solution, concentration of the Schiff base, amount of the
      surfactant, incubation temperature, and time were investigated. Under the optimum
      experimental conditions, the calibration graph was linear in the range 0.1-1300
      ng ml(-1) with a limit of detection of 0.06 ng ml(-1). The proposed method was
      successfully applied for the determination of copper in various water samples.

PMID- 19394632
TI  - Solution-phase synthesis of inorganic hollow structures by templating strategies.
AB  - The solution-phase synthesis of hollow micro- and nanostructures by using
      suitable templates such as hard templates, soft templates and reactive templates
      has attracted considerable attention in recent years. This paper is focused on
      the template synthesis of inorganic hollow structures with tailored size,
      morphology, and architecture, with emphasis on the templating strategies recently
      developed in our lab for the facile solution-phase synthesis of novel inorganic
      hollow structures. The formation mechanisms of the hollow structures via
      different kinds of templates are discussed in depth to show the general concepts
      for the preparation processes. The properties and applications of hollow
      structures are briefly described, demonstrating the promising and broad
      application fields of hollow materials.

PMID- 19394633
TI  - Controlled synthesis of CdSe and CdSe/CdS core/shell nanoparticles using Gemini
      surfactant Py-16-10-16 and their bioconjugates with BSA.
AB  - CdSe and CdSe/CdS core/shell nanoparticles (NPs) were synthesized by using Gemini
      surfactant, 1,10-bis(alpha-hexadecyl pyridine) decamethylene dibromide
      (abbreviated Py-16-10-16), as a soft template. Subsequent analysis revealed that
      the as-synthesized CdSe NPs and CdSe/CdS core/shell NPs were highly luminescent
      with quantum yields of 18% and 35%, respectively, compared with Rhodamine 6G
      (95%). Furthermore, when the nanoparticles were conjugated with bovine serum
      albumin (BSA) in PBS buffer solution (pH 7.40), the fluorescence intensity of the
      BSA system was quenched by the addition of CdSe/TGA or CdSe/CdS/TGA NPs, while
      the fluorescence intensities of CdSe/TGA and CdSe/CdS/TGA NPs were enhanced by
      the addition of BSA. This enhancement and quenching of the fluorescence intensity
      by conjugating with BSA could be used to determine the albumin concentration.

PMID- 19394634
TI  - Controlled evolution from multilamellar vesicles to hexagonal mesostructures
      through the addition of 1,3,5-trimethylbenzene.
AB  - Self-assembled porous silica materials with adjustable structures and tunable
      pore sizes have important applications in catalysis, separation, and nanoscience.
      Organic cosolvents such as 1,3,5-trimethylbenzene (TMB) can be used to synthesize
      large pore mesoporous materials. In this study, we systematically studied the
      influence of the time of TMB addition on the self-assembled organic/inorganic
      composite structures in a nonionic block copolymer templating system. By
      controlling the time at which TMB is added to the system, an evolution from
      multilamellar vesicle to ordered hexagonal mesostructure has been observed. TMB
      is a swell agent in our synthesis, an increase in the delay of TMB addition can
      kinetically reduce the amount of TMB penetrating into the hydrophobic core of
      embryonic mesostructure, leading to cooperatively self-assembled vesicular and
      mesostructured materials with decreased packing parameters. Our results have
      shown that, in the simple synthesis system of traditional SBA-15 material,
      siliceous materials with a range of structures can be rationally designed and
      synthesized through the addition of TMB at different times. Such materials with
      tunable pore structures have potential applications as microcapsules and
      controlled release/delivery carriers.

PMID- 19394635
TI  - Awareness and reactions of young stuttering children aged 2-7 years old towards
      their speech disfluency.
AB  - Awareness has been an important factor in theories of onset and development of
      stuttering. So far it has been suggested that even young children might be aware
      of their speech difficulty. The purpose of the present study was to investigate
      (a) the number of stuttering children aware of their speech difficulty, (b) the
      description of reported behavioural expression of awareness, (c) the relationship
      with age-related variables and with stuttering severity. For a total group of
      1122 children with mean age of 4 year 7 months (range 2-7 years old), parental
      reported unambiguous verbal and non-verbal reactions as a response to stuttering
      were available. In the present study, awareness is observed for 56.7% of the very
      young children (i.e., 2 years old) and gradually increases with age up until
      89.7% of the children at the age of seven. All considered age-related factors
      (i.e., chronological age, age at onset and time since onset) and stuttering
      severity are statistically significantly related to awareness. LEARNING OUTCOMES:
      Readers will be able to: (1) Describe findings of awareness of speech disfluency
      of stuttering children based on an overview of literature; (2) Describe
      methodological aspects of studies on awareness; (3) Know reported data on
      awareness of speech disfluency in young stuttering children of the present study;
      (4) Describe the relationship of awareness of speech disfluency with
      chronological age, age at onset, time since onset, gender and stuttering
      severity.

PMID- 19394636
TI  - Electrocardiographic quantification of left atrial volume: a letter on the
      article by Ariyarajah et al entitled "Formulaic quantification of
      echocardiographic left atrial volume" (J Electrocardiol. 2008 Dec 24).

PMID- 19394637
TI  - Impact of thermal injury on wound infiltration and the dermal inflammatory
      response.
AB  - Healing of the burn wound is a critical component of the burn patient's
      successful recovery. While inflammation is a critical component of the healing
      process, it is unknown whether the inflammatory response differs between non-burn
      and burn wounds. To study this, mice were subjected to major burn injury or sham
      procedure. Wound cells were collected by implantation of polyvinyl alcohol
      sponges beneath the burn site in injured mice or beneath uninjured skin in sham
      mice (i.e., non-burn wound). Three days thereafter, skin, wound fluid, and
      infiltrating cells were collected for analysis. Significant levels of tumor
      necrosis factor (TNF)-alpha, interleukin (IL-6), monocyte chemoattractant protein
      (MCP)-1, and keratinocyte-derived chemokine (KC) were observed in burn wound
      tissue and the wound fluid from both non-burn and burn wounds. Burn injury
      induced 3-fold higher levels of KC and 50-fold higher levels of IL-6 in the wound
      fluid compared with non-burn injury. Significant numbers of the cells from both
      burn and non-burn wounds were CD11b(+), GR1(+), and F4/80(+), suggestive of a
      myeloid suppressor cell phenotype, whereas CD3(+) T-cells were negligible under
      both conditions. LPS induced TNF-alpha, IL-6, IL-10, MCP-1, KC, and nitric oxide
      production in both cell populations, however, IL-6, IL-10, MCP-1, and KC levels
      were suppressed in burn wound cell cultures. These findings indicate that
      significant differences in the wound inflammatory response exist between burn and
      non-burn cutaneous wounds and that the unique characteristics of the inflammatory
      response at the burn site may be an important contributing factor to post-burn
      wound healing complications.

PMID- 19394638
TI  - Pancreatic injury response is different depending on the method of resecting the
      parenchyma.
AB  - OBJECTIVES: The present study was performed to compare the pancreatic injury
      response on the parenchymal resection either with ultrasonic scissors,
      electrocautery, or surgical scalpel. METHODS: A 1 x 0.5 cm piece of rat pancreas
      was resected from side of the pancreas either with ultrasonic scissors (Harmonic
      Scalpel; UltraCision, Ethicon Endosurgery Inc., Cincinnati, OH) or electrocautery
      (Force FX; Valleylab, Tyco Healthcare Group LP, Boulder, CO) at two power levels,
      1 and 3; 8W and 25W, respectively, or with surgical scalpel. Hemostasis was
      provided after surgical scalpel either with cellulose patch (Interceed; Johnson
      and Johnson Medical, Inc., New Brunswick, NJ), three stitches of 6-0
      polydioxanone at tightness of 0.6N or fibrin glue (Tisseel Duo Quick; Baxter AG,
      Wien, Austria). Blood sample and pancreas specimens, both at the resection site
      and far away, were taken 1, 7, and 21 days postoperatively from exposed animals,
      sham operated animals (n = 18 in each) and from unexposed baseline animals (n =
      5). Necrosis, edema, leukocyte infiltration, hemorrhage, vacuolization, and
      fibrosis were histologically assessed separately. RESULTS: Each resection and
      sham operation induced similar increase in the amylase activity on day 1 with
      normalization by day 7. Resection with ultrasonic scissors and electrocautery
      induced more tissue injury to the pancreas than resection with surgical scalpel
      independent of the method for hemostasis. The injury, although somewhat milder in
      intensity, was also observed in parts of the pancreas located far away from the
      site of resection. CONCLUSIONS: Of the compared methods, surgical scalpel
      resection plus cellulose patch or fibrin glue hemostasis induced the least
      histological changes in the pancreatic parenchyma. This injury response spread
      over the pancreas.

PMID- 19394639
TI  - Interest in internet lung cancer support among rural cardiothoracic patients.
AB  - BACKGROUND: The Internet may provide an alternative option for rural lung cancer
      patients who lack access to on-site cancer support; however, Internet access and
      use among rural patients is unknown. METHODS: An anonymous waiting-room survey
      was administered to all outpatient cardiothoracic surgery patients over 3 mo.
      Survey questions included age, gender, and diagnosis, possession of a home
      computer and Internet service, estimated Internet use, and use of the Internet
      for health information. Patients with known or suspected lung cancer were asked
      to indicate their interest in on-site and Internet cancer support. RESULTS: There
      were 597 returned surveys (response rate 96%). The mean age was 64.6 y (SE 0.55),
      and 58% were men. Diagnoses included known or possible lung cancer (15.4%), lung
      disease (9.5%), heart disease (30.4%), other diagnoses (13.9%), and undetermined
      (30.6%). There were 343 patients (57.4%) with a home computer and 299 (50.1%)
      with home Internet service. Average Internet use was 8.5 h per wk (n = 298), and
      225 patients used the Internet for health information. Of the 92 patients with
      lung cancer, 10 indicated interest in on-site support services while 37 expressed
      interest in Internet-based support. CONCLUSIONS: Based on survey results, a
      slight majority of rural patients have a home computer and Internet access.
      Internet use for health information appears relatively common. Overall interest
      for support services among lung cancer patients appears modest with a greater
      interest in Internet-based services compared with on-site support.

PMID- 19394640
TI  - Significance of portal venous VEGF during liver regeneration after hepatectomy.
AB  - BACKGROUND: Although some studies have hypothesized portal venous blood is
      important for liver regeneration, no studies have established organs whose venous
      effluent flow into the portal vein secrete liver regenerating factors into the
      portal vein during liver regeneration. The aim of this study was to elucidate up
      regulation of vascular endothelial growth factor (VEGF) in the portal vein, and
      expressions of hepatic regenerating factors in organs whose venous effluent flows
      into the portal vein during liver regeneration. MATERIALS AND METHODS: VEGF
      protein in systemic and portal venous blood, as well as expression of VEGF,
      hypoxia-inducible factor-1alfa (HIF-1alpha), hepatocyte growth factor (HGF), and
      HGF activator (HGFA) mRNA were evaluated in the regenerating liver, spleen, and
      intestine following 70% partial hepatectomy (PHx) in rats. RESULTS: The portal
      VEGF protein level was significantly higher than the systemic level post-PHx
      (portal/systemic at 72, 120, and 168 h post-PHx: 17.2/13.0, 20.2/12.8, and
      24.0/14.7 pg/mL; P = 0.003, P = 0.022 and P = 0.032, respectively). VEGF mRNA
      expressions were significantly higher in the liver (P = 0.000027: 168 h), spleen
      (P = 0.000059: 72 h) and intestine (P = 0.01: 24-72 h) post-PHx compared with pre
      PHx. HIF-1alpha, HGF, and HGFA mRNA expressions in the liver, intestine, and
      spleen were also significantly higher post-PHx compared to pre-PHx. CONCLUSIONS:
      Portal VEGF was significantly higher than systemic VEGF, and expressions of VEGF,
      HIF-1alpha, HGF, and HGFA mRNA in the liver, spleen and intestine were also up
      regulated during liver regeneration. These results suggest that hepatic
      regenerating factors derived from the spleen or intestine may contribute liver
      regeneration.

PMID- 19394641
TI  - Detection of elevated proteins in peritoneal dissemination of gastric cancer by
      analyzing mass spectra data of serum proteins.
AB  - BACKGROUND: Recently, several authors reported on the Protein Chip approach to
      analyze serum. They used SELDI-TOF-MS (surface enhanced laser
      desorption/ionization-time of flight-mass spectrometry) to identify patients with
      cancers of various origins in a highly sensitive and specific manner. In the
      current study, a similar approach was employed to analyze the serum of patients
      with various stages of gastric cancer. METHODS: Control serum specimens from
      patients with gastritis (n = 19) and those with gastric cancer (Stage I: n = 6,
      Stage II or III: n = 6, Stage IV: n = 6, total: n = 18) were collected and
      analyzed by the Protein Chip biomarker system (Bio-Rad, Japan), a platform for
      SELDI-TOF-MS, and protein profiles were obtained and compared. The cation
      exchange chip (CM10) and the anion exchange chip (Q10) were used for processing
      before TOF-MS. RESULTS: nine proteins were significantly over-expressed (P <
      0.05, Student t-test) in patients with gastric cancer compared to patients with
      gastritis. Among them, four protein masses with 2929 m/z, 3293 m/z, 3371 m/z, and
      4213 m/z were found to be differentially expressed solely in patients suffering
      from peritoneal dissemination. All peaks were processed on CM10 chips. Employing
      one data mining method, CART (classification and regression trees), gastric
      cancer patients with peritoneal dissemination were successfully separated from
      those who had no peritoneal seeding. CONCLUSION: A validation study with a larger
      number of samples is mandatory; however, the detected peaks here might be
      candidates for biomarkers of peritoneal dissemination and/or gastric cancer.
      Moreover, further analysis of these four proteins might be helpful in revealing
      the mechanism of peritoneal dissemination, which at present has no cure.

PMID- 19394642
TI  - Attenuation of liver ischemia/reperfusion induced apoptosis by epigallocatechin-3
      gallate via down-regulation of NF-kappaB and c-Jun expression.
AB  - INTRODUCTION: Hepatic ischemia/reperfusion (I/R) activates Kupffer cells and
      initiates severe oxidative stress with enhanced production of reactive oxygen
      species (ROS) and tumor necrosis factor-alpha (TNF-alpha). ROS and TNF-alpha
      mediate the expression of nuclear factors and kinases, activating the signal
      transduction pathway, and triggering apoptosis. The aim of our study was to
      evaluate the potential protective effect of (-)-epigallocatechin-3-gallate (EGCG)
      administration in inhibition of apoptosis by attenuating the expression of NF
      kappaB, c-Jun, and caspase-3 in a model of severe hepatic I/R. MATERIALS AND
      METHODS: Thirty Wistar rats were allocated into three groups. Sham operation,
      I/R, and I/R-EGCG 50mg/kg. Hepatic ischemia was induced for 60min by Pringle's
      maneuver. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, scanning
      electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL), and immunocytochemistry for NF-kappaB, c-Jun, caspase-3, analysis on
      liver specimens and aspartate (AST), and alanine (ALT) transferases analysis in
      serum, were performed 120min after reperfusion. RESULTS: Apoptosis as indicated
      by TUNEL and caspase-3 was widely expressed in the I/R group but very limited in
      the EGCG treated group. Liver was stained positive for NF-kappaB and c-Jun in the
      I/R group but failed to be stained positive in the EGCG treated group. MDA, MPO,
      AST, and ALT showed marked increase in the I/R group and significant decrease in
      EGCG treated group. Significant alterations of liver specimens were observed by
      light histology and transmission electron microscopy whilst pretreatment with
      EGCG resulted in parenchymal preservation. CONCLUSIONS: Administration of EGCG is
      likely to inhibit I/R-induced apoptosis and protect liver by down-regulating NF
      kappaB and c-Jun signal transduction pathways.

PMID- 19394643
TI  - A randomized clinical study evaluating the need for drainage after Limberg flap
      for pilonidal sinus.
AB  - BACKGROUND: This prospective randomized clinical study was conducted to evaluate
      the need for drainage after rhomboid excision and a Limberg flap (RELIF) for the
      treatment of pilonidal sinus. METHODS: One hundred one patients undergoing the
      RELIF procedure were randomly treated with drainage or not. Operating time,
      postoperative pain assessed on a visual analogue scale (VAS), total amount of
      intramuscular analgesic administered, hospital stay, complications, recurrence
      rate, and patient satisfaction were assessed. RESULTS: The mean operating time (P
      = 0.036), VAS scores on postoperative day 0 (P = 0.039) and day 1 (P = 0.006),
      intramuscular analgesic requirement (P = 0.009), mean amount of intramuscular
      analgesic administered (P = 0.025), complication rate (P = 0.027), and mean
      hospital stay (P = 0.0001) were significantly reduced in the non-drained group.
      The recurrence rate was similar in the two groups (P = 0.32). CONCLUSIONS: This
      study indicates that drain placement after the RELIF procedure might negatively
      affect the postoperative outcomes of patients with pilonidal sinus. On the basis
      of these finding, we suggest that the use of drains may not be necessary after
      the RELIF procedure for the treatment of pilonidal sinus.

PMID- 19394644
TI  - Effects of NO/L-arginine pathway on gallbladder contractility in bile duct
      ligated guinea pigs.
AB  - BACKGROUND: Common bile duct ligation (CBDL) produces gallbladder distension and
      acute inflammation similar to that seen in human acute acalculous cholecystitis.
      CBDL in the guinea pig affects smooth muscle contractility. The aim of this study
      was to determine whether the nitric oxide-L-arginine pathway plays a role in the
      inflammatory process and abnormal gallbladder contractility that occur after
      CBDL. MATERIALS AND METHODS: Contractility of gallbladder muscle from CBDL and
      sham-operated guinea pigs was studied in vitro. Animals were treated with saline,
      aminoguanidine (AG), or an aminoguanidine + L-arginine combination (AG + L-Arg)
      in vivo. Potassium chloride, carbachol, and electric field stimulation (EFS) were
      used for contracting the gallbladder muscle strips or activating intrinsic
      nerves. Hematoxylin and eosin-stained slides of muscle strips were scored for
      inflammation. RESULTS: Contraction responses to carbachol and EFS were decreased
      significantly in CBDL guinea pigs compared with those in the sham-operated group.
      AG partly reversed the smooth muscle contractile response to carbachol and EFS,
      but did not reduce the inflammation score. Treatment with AG + L-arg did not
      reverse either the contraction response or the inflammation score. CONCLUSIONS:
      These findings suggest that AG and AG + L-Arg treatments have no beneficial
      effect on inflammation in guinea pigs after CBDL, although AG significantly
      reversed the effect on muscle contractility (P < 0.05). This improvement was
      independent of inflammation and may be due to a decreased level of NO and its
      diminished relaxant effect.

PMID- 19394645
TI  - Interleukin-18 exacerbates pulmonary injury after hepatic ischemia/reperfusion in
      mice.
AB  - BACKGROUND: Hepatic ischemia/reperfusion has been shown to cause both local
      hepatic and distant organ (such as lung) injury caused by accumulation of
      neutrophils in the local and distant organs, leading to neutrophil-dependent
      organ injury. Interleukin (IL) -18 is required for facilitating neutrophil
      dependent local hepatic injury by suppressing anti-inflammatory cytokine
      expression, but less is known about the involvement of this cytokine in distant
      organ injury. The objective of this study was to determine whether IL-18
      contributes to pulmonary injury induced by hepatic ischemia/reperfusion. METHODS:
      C57BL/6 mice and IL-18 knockout mice (C57BL/6 background) were subjected to 90
      min of partial hepatic ischemia and subsequent reperfusion. Neutrophil
      accumulation in the lung was assessed by pulmonary myeloperoxidase contents.
      Pulmonary expressions of keratinocyte derived chemokine (KC, CXCL1), macrophage
      chemoattractant protein-1 (MCP-1, CCL2), tumor necrosis factor-alpha, interferon
      gamma, IL-4, and IL-10 were measured by tissue enzyme-linked immunosorbent assay
      (ELISA). Lung edema was quantified by the pulmonary wet to dry weight ratios.
      RESULTS: Hepatic ischemia/reperfusion caused significant increases in pulmonary
      neutrophil recruitment and lung edema. Also, pulmonary expression of KC and MCP-1
      were up-regulated. In the IL-18 knockout mice, hepatic ischemia/reperfusion
      induced increases in pulmonary neutrophil recruitment, lung injury defined by
      lung edema, and pulmonary chemokine expression were attenuated. Furthermore,
      pulmonary expression of an anti-inflammatory cytokine IL-4 and systemic IL-10
      expression were significantly up-regulated in the IL-18 knockout mice.
      CONCLUSIONS: The data suggested that IL-18 plays an important role in the
      development of pulmonary injury after hepatic ischemia/reperfusion by up
      regulating proinflammatory mediators and possibly suppressing anti-inflammatory
      cytokine expression.

PMID- 19394646
TI  - Assessment of pancreatic hardness-surgeon versus durometer.
AB  - BACKGROUND: This study reports the first results of durometrically measured
      hardness of human pancreas and investigates its correlation to palpatory
      determined hardness, grade of pancreatic fibrosis, and preoperatively determined
      radiodensity. METHODS: Fifty-two patients with pancreatic resections were
      prospectively recruited. Hardness of samples from pancreatic cancer, chronic
      pancreatitis, and normal pancreas was measured using a durometer on a 0-100 Shore
      units (SU) scale. Three pancreatic surgeons palpated the pancreas and reported
      their assessment of hardness on a subjective 0-100 "Bochum units" (BU) scale.
      Radiodensity and fibrosis of pancreatic tissue were used for comparison. RESULTS:
      Pancreatic hardness differed significantly in normal pancreas, chronic
      pancreatitis, and pancreatic cancer; 30 SU, 51 SU, and 65.8 SU, respectively.
      Palpatory hardness of normal pancreas was 20 BU and of pancreatitis 60 BU. It
      correlated well to durometric readings: r(2)=0.56, P<0.00001. Fibrosis grade and
      radiodensity correlated neither to durometry nor to palpation. Pancreatic leak
      developed 4/20 (20%) patients with normal pancreas vs. 1/32 (3.1%) with chronic
      pancreatitis in the resection margin, P<0.05. CONCLUSIONS: Palpatory assessment
      of pancreatic hardness performed by experienced surgeons correlated well to
      durometric measurements and remains the method of choice for intraoperative
      decision making. Durometry was more precise and should be considered in studies
      on pancreatic texture and for teaching purposes. Hardness and fibrosis grade
      appeared to be independent characteristics of pancreatic texture.

PMID- 19394647
TI  - Radiofrequency ablation of liver tumors: a novel needle perfusion technique
      enhances efficiency.
AB  - OBJECTIVE: We hypothesize that perfusion of an expandable radiofrequency ablation
      (RFA) needle with saline solution might help prevent charring and increase
      efficiency. SUMMARY BACKGROUND DATA: RFA has become an important adjunct to
      modern liver surgery. However, ablation is time-consuming and hazardous due to
      charring around the radiofrequency electrodes. METHODS: From June 2000 to
      November 2004, 159 liver tumors with a median diameter of 2.0 cm were treated
      with RFA, 54 tumors of them according to the manufacturer's standard protocol and
      105 tumors according to the novel perfusion protocol. No randomization was
      applied. All patients were followed up with contrast enhanced computed tomography
      (CT) at regular intervals. Local recurrence was defined as radiologic and/or
      histologic evidence of viable tumor within or at the ablated liver area. RESULTS:
      Both study groups were comparable with regard to tumor characteristics, procedure
      related complications, and median times of follow-up (27 mo in the standard group
      versus 23 mo in the perfusion group). The median RFA time was significantly
      reduced from 18.9 min in the standard group to 8.0 min in the perfusion group.
      The rates of incomplete ablations were comparable in both groups (3.7% versus
      2.8%). The rate of local recurrences at the RFA site was 6.9% overall, 11.1% in
      the standard group, and 4.8% in the perfusion group. No tumor seeding along the
      puncture channel was observed. CONCLUSIONS: The perfusion of an expandable RFA
      needle with saline solution significantly accelerates the ablation procedure of
      liver tumors without increase of complications and without compromising the
      oncosurgical result.

PMID- 19394648
TI  - The effects of intravenous hyperoxygenated solution infusion on systemic
      oxygenation and intrapulmonary shunt during one-lung ventilation in pigs.
AB  - BACKGROUND: Many anesthetic methods have been applied to maintain acceptable
      oxygenation during one-lung ventilation (OLV). However, the optimal management
      has not been definitely determined. The aim of this study was to investigate
      whether intravenous hyperoxygenated solution (HOS) infusion would improve
      systemic oxygenation and reduce intrapulmonary shunt during OLV. MATERIALS AND
      METHODS: Sixteen pigs (25-35 kg) were anesthetized, tracheally intubated, and
      mechanically ventilated. After placement of femoral artery and pulmonary artery
      catheters, a left-sided double-lumen tube (DLT) was placed via tracheotomy. The
      animals were allocated randomly to one of the two study groups (n = 8 each);
      control group (C group) and hyperoxygenated solution group (H group). Animals in
      H group received intravenous HOS infusion immediately after the beginning of OLV
      via internal right jugular vein with an infusion pump, and the rate of infusion
      was 15 mL.kg(-l).h(-l); and in C group, the same amount of lactate Ringer's
      solution (LRS) was used in place of HOS. Arterial and venous blood gases analysis
      were recorded in three phases: during two-lung ventilation just before beginning
      OLV (TLV), 30 min after beginning OLV (OLV + 30), and 60 min after beginning OLV
      (OLV + 60). We measured arterial oxygen saturation (SaO(2)), mixing venous oxygen
      saturation (S(V)O(2)), partial pressure of arterial oxygen (PaO(2)), partial
      pressure of mixing venous oxygen (PvO(2),) oxygen contents in systemic arterial
      and mixed venous blood (CaO(2), CvO(2)), and venous admixture percentage
      (Qs/Qt%). Heart rate (HR), mean arterial pressure (MAP), mean pulmonary artery
      pressure (MPAP), and cardiac output (CO) were also recorded. RESULTS: After 30
      and 60 min OLV, there was a significant decrease in PaO(2), SaO(2), PvO(2),
      SvO(2), CaO(2), and CvO(2), and a significant increase of Qs/Qt% in both groups
      (P < 0.01). The values of PaO(2), SaO(2), PvO(2), SvO(2), and CvO(2) in H group
      at both OLV + 30 and OLV + 60 were significantly higher than those in C group (P
      < 0.05, P < 0.01). Although the values of CaO(2) in H group were higher than
      those in C group at OLV + 30 and OLV + 60, there were no significant differences.
      Comparing the values of Qs/Qt% between the two groups at OLV + 30 and OLV + 60,
      there were also no significant differences. CONCLUSIONS: Intravenous HOS infusion
      led to minimal changes in intrapulmonary shunt, nevertheless, it could ameliorate
      arterial oxygenation obviously during OLV. This might be a new strategy to
      improve systemic oxygenation during OLV.

PMID- 19394649
TI  - Omental roll-up: a technique for islet engraftment in a large animal model.
AB  - BACKGROUND: Attrition of transplanted islets is significant after hepatic
      embolization. This study was designed to investigate a novel surgical technique
      for islet transplantation into the omentum. This site allows placement of the
      islets in a three-dimensional (3D) matrix, with growth factors, to temporarily
      culture the islets in vivo while revascularization progresses. MATERIALS AND
      METHODS: Five female dogs (three partial and two total pancreatectomies) received
      an autologous islet transplant in the omentum. Islets were suspended in 1 mL of
      PBS containing 10 ug of vascular endothelial growth factor (VEGF). Fresh
      autologous plasma (10 mL) was mixed with the islet/VEGF suspension. The coagulum
      containing the islets and VEGF was then placed on the greater omentum. The
      leading edge of omentum was rolled up to secure the islet/VEGF/coagulum in
      position and to present the thin islet layer with two omental surfaces for
      implantation. Omentum was recovered at 2, 13, 21, 42, and 180 d. RESULTS:
      Immunohistochemical staining for synaptophysin, glucagon, and insulin confirmed
      the presence of transplanted islets in all omenta. Insulin and C peptide
      production from the omental islets was confirmed in portal venous samples, and
      normalization of morning glucose levels beginning on day 7 was seen in the total
      pancreatectomy experiment. CONCLUSIONS: Autologous islets implant in rolled-up
      omentum when placed as a VEGF/autologous plasma coagulum. This technique has
      potential benefits, including the opportunity to accelerate revascularization and
      to investigate local strategies for modulating the immune response.

PMID- 19394650
TI  - Development of a sleeve gastrectomy weight loss model in obese Zucker rats.
AB  - BACKGROUND: Obesity promotes the development of diabetes and cardiovascular
      disease. The most effective weight loss treatment is bariatric surgery, but
      results greatly vary depending on the procedure. Sleeve gastrectomy (SG) has
      recently emerged as a reduced risk weight loss procedure for super obese
      patients. However, the mechanism of weight loss from SG and its effects on
      obesity-induced complications are yet to be determined. Our goal was to develop
      an experimental model of SG in genetically obese rats. MATERIALS AND METHODS:
      Male obese Zucker rats (400-500 g, leptin-insensitive) were anesthetized with
      isoflurane. After a midline laparotomy, the stomach was clamped, the greater
      curvature was excised, and a triple suture line was used to close the gastric
      remnant. Sham rats underwent laparotomy only. Metabolic parameters were followed
      for 14 d after surgery. RESULTS: Caloric intake and body weight decreased in SG
      rats over 14 d by 98 +/- 10 kcal/d and 74 +/- 14 g, respectively. Blood total
      cholesterol levels were lower in rats that lost weight. Furthermore, blood
      glucose levels were lower in rats that lost weight. Active ghrelin levels were
      unchanged in SG rats 14 d after surgery. CONCLUSIONS: These results show that SG
      promotes weight loss in obese Zucker rats. Furthermore, SG-induced weight loss is
      accompanied by improved plasma cholesterol and glucose profile. However, SG does
      not promote a prolonged decrease in ghrelin levels. These results suggest that SG
      is an effective weight loss procedure in leptin insensitivity to improve the
      lipid profile and decrease insulin resistance and these effects might be
      independent of changes in ghrelin levels.

PMID- 19394651
TI  - Anti-angiogenic therapy on hepatocellular carcinoma development and progression.
AB  - BACKGROUND: The hypervascular nature of hepatocellular carcinoma (HCC) has led a
      number of investigators to explore the potential of anti-angiogenic therapy for
      this cancer. We aimed to investigate the efficacy of anti-angiogenetic therapy
      for the prevention and treatment of HCC. METHODS: An experimental model of HCC
      induced by diethylnitrosamine (DEN) was used in this study as a model resembling
      human HCC. Because endothelial cells play a central role in angiogenesis, FR
      118487 (FR) with a direct effect on endothelial cells was selected for use in
      this study. FR-treated rats were divided into three groups of five animals each
      according to the timing of FR treatment, i.e., at the initiation of exposure to
      DEN (group I), after 6 wk of DEN exposure (group II), and after 12 wk of DEN
      exposure (group III). RESULTS: No macroscopic nodules were observed in group I.
      Moreover, no significant difference in the mean maximum diameter and number of
      HCC nodules were found between the control group at 12 wk and group III at 18 wk.
      Thus, FR was shown to have a chemopreventive effect in addition to causing
      dormancy of HCC. The results obtained, including IL-8 levels, reflected the
      effect on HCC of anti-angiogenic therapy with FR. CONCLUSION: Anti-angiogenic
      therapy may be effective for both chemoprevention and tumor dormancy in HCC
      associated with chronic liver disease. IL-8 may be useful as a marker of the
      efficacy of anti-angiogenic therapy for HCC.

PMID- 19394652
TI  - Pharmacological synergism between cannabinoids and paclitaxel in gastric cancer
      cell lines.
AB  - Orally applicable Delta9-tetrahydrocannabinol and its synthetic derivatives have
      been used as antiemetic drugs during chemotherapy in cancer patients. However, it
      is not well known how cannabinoids influence the effects of chemotherapeutic
      agents on malignant tumors. In this study, we investigated how the endogenous
      cannabinoid anandamide (AEA) changes the effect of paclitaxel on gastric cancer
      cell lines. In the human gastric cancer cell line, HGC-27, which express
      cannabinoid receptor 1 (CB1), AEA stimulated proliferation at concentrations
      under 1 microM, while it strongly suppressed proliferation through the induction
      of apoptosis at 10 microM. This bimodal effect was reproduced by a selective CB1
      agonist, arachidonyl-2-chloroethylamide, although the effects were less marked.
      When AEA was used with paclitaxel, AEA at 10 microM synergistically enhanced the
      cytotoxic effect of paclitaxel, whereas it showed no significant effect at lower
      concentrations. Flow cytometric analysis revealed that addition of 10 microM AEA
      synergistically enhanced paclitaxel-induced apoptosis, possibly through the
      activation of caspase-3, -8, and -9. Our results suggest that cannabinoids could
      be a good palliative agent for cancer patients receiving paclitaxel.

PMID- 19394653
TI  - Integrin and matrix metalloproteinase expression in human carotid plaque.
AB  - BACKGROUND: Neointimal thickening is the major cause of restenosis after carotid
      endarterectomy (CEA) and carotid stenting. The biologic behavior of these lesions
      is regulated by the interaction between smooth muscle cells (SMCs), endothelial
      cells (ECs), and extracellular matrix (ECM) proteins. Although the contribution
      of the cellular components of neointimal lesions has been extensively studied,
      the role of the ECM proteins in lesion remodeling is less well defined. METHODS:
      We examined primary and restenotic carotid endarterectomy specimens to determine
      their cellular morphology. Tissue was also preserved for protein extraction for
      Western immunoblotting and mRNA for RT-PCR and cDNA microarray analysis. RESULTS:
      All primary lesions demonstrated the features of complex atherosclerotic plaque.
      Restenotic lesions were composed of SMCs embedded in ECM. Microarray analysis
      demonstrated altered expression of 13 of 96 genes. Eight genes were increased
      more than 3-fold and five genes were decreased more than 3-fold in primary plaque
      compared with restenotic lesions. RT-PCR confirmed alpha2-, alpha6-, and beta3
      integrin gene expression in reference tissue, primary plaque, and restenotic
      lesions, with the greatest expression in primary plaque. Primary plaque
      demonstrated increased protein expression of plasminogen activator inhibitor-1
      (PAI-1) and tissue inhibitor of metalloproteinase (TIMP-1). By zymography, pro
      MMP-2, pro-MMP-9 levels, and MMP-2 activity were also increased in primary plaque
      compared with reference and restenotic tissues. CONCLUSIONS: The decreased
      integrin expression and protease activity in restenotic lesions versus primary
      carotid plaques suggests that the neointimal lesions were in a quiescent phase.
      These alterations in protein expression and protease activity demonstrate the
      importance of proteinase/inhibitor imbalance in regulating plaque remodeling.

PMID- 19394654
TI  - Angiogenic gene-modified fibroblasts for induction of localized angiogenesis.
AB  - BACKGROUND: Induction of localized angiogenesis is of particular interest in the
      field of plastic surgery. Topical application of recombined vascular endothelial
      growth factor (VEGF) shows only little effect on graft healing. This study
      describes the establishment of an ex vivo engineered VEGF slow release system
      based on autogenous fibroblasts. METHODS: Primary fibroblasts were subjected to
      nucleofection and analyzed for transgene expression 1, 2, 3, 4, 7, and 9 d post
      nucleofection using FACS. VEGF transgene expression was measured in cell culture
      supernatants using ELISA. Transgenic protein functionality was examined in the
      HUVEC proliferation assay. The effect of VEGF transgene expression on the
      neovascularization of a collagen membrane was investigated in a rat model.
      RESULTS: Primary fibroblasts were nucleofected with an efficiency of 63.331% and
      transgene expression showed persistence up to day 9 post-nucleofection. VEGF was
      expressed in the cell culture up to day 14 with an expression peak at day 3. The
      cytokine was functionally active. VEGF transgene was released in vivo at day 7
      and enhanced neovascularization of a collagen membrane. CONCLUSIONS:
      Nucleofection is the ideal nonviral tool to engineer transgenic primary
      fibroblasts for transplantation purpose in an ex vivo gene therapeutic approach.
      Such ex vivo gene therapy is safe and efficient. Its suitability should be
      further evaluated in more complex flap models, for example the transfer of a free
      myocutaneous gracilis flap in the pre-irradiated neck region.

PMID- 19394655
TI  - Serum from radiofrequency-injured livers induces differentiation of bone marrow
      stem cells into hepatocyte-like cells.
AB  - BACKGROUND: Roles that bone marrow stem cells (BMSCs) play in liver repair after
      liver injury and the cell therapy for liver diseases are widely accepted.
      However, the availability of hepatocyte-like cells from BMSCs and possible animal
      diseases association with culturing in fetal calf serum (FCS) are the major
      limitations of clinical therapy. Therefore, this study was designed to search for
      a new cell source for the treatment of liver injuries through investigating
      whether serum from radiofrequency ablation-injured rabbit livers can induce the
      differentiation of BMSCs into hepatocyte-like cells. METHODS: Serum was collected
      from rabbits 36 h after radiofrequency ablation (RFA) treatment of the liver.
      BMSCs were isolated from rabbit bone marrow and were cultured in the collected
      serum. Cellular morphology and cell cycle were observed. Hepatocyte markers of
      the differentiated cells were detected by immunohistochemistry. RESULTS: After
      induction for 7 d, spindle-shaped BMSCs turned into round cells that resembled
      the morphology of hepatocyte-like cells. Flow cytometry showed that the
      percentage of cells in the S/G2/M phase was higher in the RFA group than that in
      the FCS group and HGF groups. This result suggests that BMSC can transform into
      mature cells from stem cell phase. Albumin and CK18 were considered as typical
      marker of hepatocytes. Following induction for 14 d, the differentiated cells
      expressed immunofluorescence of FITC-labeled albumin and TRITC-labeled CK18.
      CONCLUSION: BMSCs treated with serum collected from radiofrequency ablation
      injured livers can differentiate into hepatocyte-like cells providing a cell
      source to cell therapy.

PMID- 19394656
TI  - Melatonin and 1400 W ameliorate both intestinal and remote organ injury following
      mesenteric ischemia/reperfusion.
AB  - OBJECTIVE: Acute intestinal ischemia reperfusion (I/R) injury affects not only
      the intestines but also remote organs due to pro-inflammatory and tissue
      injurious factors. Thus, we aimed to investigate the roles of melatonin (a
      powerful antioxidant) and 1400W (a strong inhibitor of inducible nitric oxide) in
      a rat intestinal I/R injury model, since oxidative and nitrosative injury are
      believed to be the major causes. METHODS: A total of 56 Wistar albino rats were
      used, with seven rats in each group. After I/R induction in the intestines by
      clamping/unclamping the superior mesenteric artery, we measured malondialdehyde,
      superoxide dismutase, glutathione peroxidase, nitric oxide, and 3-nitrotyrosine
      levels in lung, kidney, and liver tissues (to evaluate remote organ injury) as
      well as in the intestines. Study groups received melatonin, 1400W or both to
      examine the roles of these molecules in the pathogenesis of injury following I/R.
      RESULTS: Melatonin and 1400W had an ameliorating effect on both oxidative and
      nitrosative stress in the intestine and the lung against mesenteric I/R injury in
      rats. Moreover, each of these two agents had an inhibitory effect on oxidative
      injury and histopathological changes in the intestine and the lung. Furthermore,
      the combination of both agents (melatonin and 1400W) was more effective than
      either of the agents alone (P < 0.05). CONCLUSION: Melatonin and 1400W, either
      alone or in combination, were efficient in ameliorating experimental I/R injury
      of the intestines.

PMID- 19394657
TI  - Bivalves as indicators of environmental variation and potential anthropogenic
      impacts in the southern Barents Sea.
AB  - Identifying patterns and drivers of natural variability in populations is
      necessary to gauge potential effects of climatic change and the expected
      increases in commercial activities in the Arctic on communities and ecosystems.
      We analyzed growth rates and shell geochemistry of the circumpolar Greenland
      smooth cockle, Serripes groenlandicus, from the southern Barents Sea over almost
      70 years between 1882 and 1968. The datasets were calibrated via annually
      deposited growth lines, and growth, stable isotope (delta(18)O, delta(13)C), and
      trace elemental (Mg, Sr, Ba, Mn) patterns were linked to environmental variations
      on weekly to decadal scales. Standardized growth indices revealed an oscillatory
      growth pattern with a multi-year periodicity, which was inversely related to the
      North Atlantic Oscillation Index (NAO), and positively related to local river
      discharge. Up to 60% of the annual variability in Ba/Ca could be explained by
      variations in river discharge at the site closest to the rivers, but the
      relationship disappeared at a more distant location. Patterns of delta(18)O,
      delta(13)C, and Sr/Ca together provide evidence that bivalve growth ceases at
      elevated temperatures during the fall and recommences at the coldest temperatures
      in the early spring, with the implication that food, rather than temperature, is
      the primary driver of bivalve growth. The multi-proxy approach of combining the
      annually integrated information from the growth results and higher resolution
      geochemical results yielded a robust interpretation of biophysical coupling in
      the region over temporal and spatial scales. We thus demonstrate that
      sclerochronological proxies can be useful retrospective analytical tools for
      establishing a baseline of ecosystem variability in assessing potential combined
      impacts of climatic change and increasing commercial activities on Arctic
      communities.

PMID- 19394658
TI  - Polychlorinated dibenzo-p-dioxin (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) in harbor sediments from Sea Lots, Port-of-Spain, Trinidad and Tobago.

PMID- 19394659
TI  - [Sweet's syndrome].
AB  - Sweet's syndrome represents the epitome of the neutrophilic dermatosis, a group
      of reactive cutaneous diseases characterized histopathologically by the existence
      of an infiltrate composed by neutrophils. Clinically, it is characterized by the
      abrupt onset of tender or painful plaques accompanied by fever, general malaise,
      and neutrophilic leukocytosis. Sweet's syndrome is a marker of several internal
      conditions, especially infections, inflammatory bowel disease, autoimmune
      disorders, and malignant neoplasm (predominantly of hematological origin).
      Sweet's syndrome reflects a neutrophilic reaction that affects the skin and
      sometimes internal organs. For this reason it is important to reach a correct
      diagnosis and assess appropriately both the triggering factors and the
      concomitant internal involvement. There are several therapeutic approaches that
      achieve either the resolution or the satisfactory management of this condition.

PMID- 19394660
TI  - Men develop more intraabdominal obesity and signs of the metabolic syndrome after
      hyperalimentation than women.
AB  - We prospectively studied the effects of fast food-based hyperalimentation on
      insulin sensitivity and components of the metabolic syndrome and analyzed this
      with respect to sex. Twelve nonobese men and 6 nonobese women (26 +/- 6.6 years
      old), and an age-matched control group were recruited. Subjects in the
      intervention group aimed for 5% to 15% weight increase by doubling their regular
      caloric intake based on at least 2 fast food meals a day while also adopting a
      sedentary lifestyle for 4 weeks (<5000 steps a day). Weight of subjects in the
      intervention group increased from 67.6 +/- 9.1 to 74.0 +/- 11 kg (P < .001), with
      no sex difference with regard to this or with respect to changes of total
      abdominal fat volumes or waist circumferences. Fasting insulin (men: before, 3.8
      +/- 1.7 microU/mL; after, 7.4 +/- 3.1 microU/mL; P = .004; women: before, 4.9 +/-
      2.3 microU/mL; after, 5.9 +/- 2.8 microU/mL; P = .17), systolic blood pressure
      (men: before, 117 +/- 13 mm Hg; after, 127 +/- 9.1 mm Hg; P = .002; women:
      before, 102 +/- 5.1 mm Hg; after, 98 +/- 5.4 mm Hg; P = .39), serum low-density
      lipoprotein cholesterol, and apolipoprotein B increased only in the men of the
      intervention group. The sex differences in the metabolic responses to the
      intervention were linked to a considerable difference in the fat accumulation
      pattern; 41.4% +/- 9.2% of the increase of the fat volume in the abdominal region
      was accumulated intraabdominally in men and 22.7 +/- 6.5% in women (P < .0001).
      This study thus showed that women are protected, compared with men, against
      developing intraabdominal obesity when adopting a standardized obesity-provoking
      lifestyle. Our findings suggest that it is not different lifestyles and/or
      behaviors that underlie the fact that men have a higher cardiovascular risk at
      the same level of percentage of body fat than women.

PMID- 19394661
TI  - Impact of rosiglitazone and glyburide on nitrosative stress and myocardial blood
      flow regulation in type 2 diabetes mellitus.
AB  - Cardiovascular disease, the leading cause of death in patients with type 2
      diabetes mellitus (T2DM), is usually preceded by endothelial dysfunction and
      altered myocardial blood flow (MBF) regulation. Hyperglycemia, oxidative
      nitrosative stress, systemic inflammation, and insulin resistance are implicated
      in the pathogenesis of abnormal MBF regulation, myocardial ischemia, and
      apoptosis. However, the impact of oral antihyperglycemic therapy on myocardial
      perfusion is controversial. Our objective was to explore the effect of
      rosiglitazone and glyburide on nitrosative stress and MBF regulation in subjects
      with T2DM. [(13)N]ammonia positron emission tomography and cold pressor testing
      were used in 27 diabetic subjects (mean age, 49 +/- 11 years; glycohemoglobin, 7%
      +/- 1.5%) randomized to either rosiglitazone 8 mg/d or glyburide 10 mg/d for 6
      months. Isotope dilution gas chromatography-mass spectrometry was used to
      quantify plasma 3-nitrotyrosine, a stable marker of reactive nitrogen species. At
      6 months, there were no significant differences between groups in the mean
      glycohemoglobin, blood pressure, or plasma lipids. Rosiglitazone significantly
      reduced plasma nitrotyrosine, high-sensitivity C-reactive protein, and von
      Willebrand antigen (P < .03 for all) and significantly increased plasma
      adiponectin (P < .05). No significant changes in these parameters were observed
      with glyburide. Treatment with glyburide, but not rosiglitazone, resulted in a
      significant deterioration in both resting and stress MBF. Rosiglitazone, but not
      glyburide, ameliorated markers of nitrosative stress and inflammation in subjects
      with T2DM without impairing myocardial perfusion.

PMID- 19394662
TI  - Application of human mini-satellite VNTR probes to genotyping in cynomolgus
      macaques.
AB  - Cynomolgus macaques (also known as longtail or crab-eating macaques) Macaca
      fascicularis, are an important non-human primate model for biomedical research.
      Using a case study involving a suspected occurrence of twin birth, we demonstrate
      that the highly polymorphic human variable-number tandem repeat (VNTR) mini
      satellite probes D1S7, D2S44, D3S42 and D4S184 can be successfully employed as a
      rapid screening strategy to complement husbandry records in order to establish
      genetic relatedness in a captive colony.

PMID- 19394663
TI  - Absence of an impact of resistance to chloroquine on consultations for malaria in
      Niakhar, Senegal (1992-2004).
AB  - We retrospectively assessed the impact of chloroquine (CQ) resistance in the
      rural region of Niakhar, Senegal, where resistance to CQ emerged in 1992, from
      increases in consultations and returns of patients to the health centre following
      antimalarial treatment. No significant differences were observed between 1992,
      when chemoresistance appeared, and 2004, when first-line treatment of malaria
      changed, except in the private centre where practices and follow-up were
      distinct. In this zone of Senegal, resistance to CQ does not appear to have a
      high impact on malaria morbidity in health centres.

PMID- 19394664
TI  - Evaluation of directly observed therapy for tuberculosis in KwaZulu-Natal, South
      Africa.
AB  - Tuberculosis (TB) is one of the leading causes of morbidity and mortality in
      KwaZulu-Natal (KZN), South Africa. Directly observed therapy (DOT) is a key
      element of the WHO's Directly Observed Treatment, Short Course (DOTS) strategy to
      control TB. Since the inception of DOTS in South Africa in 1996, its impact has
      never been assessed. We evaluated the DOT programme in the priority facilities of
      the four TB crises districts (EThekwini, UMgungundlovu, UMzinyathi and UThungulu)
      in the province of KwaZulu-Natal. A semi-structured questionnaire was used to
      interview TB nurses and community DOT supporters. The primary outcome used was
      cure rate. On average, priority facilities in districts that have high DOT
      coverage had better cure rates compared with those that have low DOT coverage
      (beta=0.818, 95% CI 0.023-1.614; P=0.045). The fewer the number of patients
      allocated to a DOT supporter the higher the cure rates (beta=-1.984; 95% CI -3.88
      to 0.086; P=0.041). There was no difference in cure rates between facilities with
      tangible reporting and recording methods and those with none. These findings
      suggest that cure rates can be improved if DOT is implemented appropriately.

PMID- 19394665
TI  - Severe acute respiratory syndrome coronavirus accessory protein 9b is a virion
      associated protein.
AB  - Eight accessory proteins have been identified in severe acute respiratory
      syndrome-associated coronavirus (SARS-CoV). They are believed to play roles in
      the viral life cycle and may contribute to the pathogenesis and virulence. ORF9b
      as one of these accessory proteins is located in subgenomic mRNA9 and encodes a
      98 amino acid protein. However, whether 9b protein is a structural component of
      SARS-CoV particles remains unknown. In this study, we demonstrate that 9b protein
      is translated from bicistronic mRNA9 via leaky ribosome scanning and it is
      incorporated into both virus-like particles (VLPs) and purified SARS-CoV virions.
      Further analysis shows that sufficient incorporation of 9b protein into VLPs is
      dependent upon the co-expression of E and M proteins, but not upon the presence
      of either S or N protein. Our data indicate that 9b protein of SARS-CoV is
      another virion-associated accessory protein. This finding will lead to a better
      understanding of the properties of the SARS-CoV 9b protein.

PMID- 19394666
TI  - Effect of 6 alpha,7 beta-dihydroxyvouacapan-17 beta-oic acid and its lactone
      derivatives on the growth of human cancer cells.
AB  - The furanditerpene 6 alpha,7 beta-dihydroxyvouacapan-17 beta-oic acid (1) is a
      natural product biosynthesized by some species from the genus Pterodon
      (Leguminosae). This secondary metabolite has multiple biological activities that
      include anti-inflammatory, analgesic, plant growth regulatory, anti-edematogenic,
      photosystem II inhibitory and photosynthesis uncoupler, and antifungal
      properties. However, few studies on the antiproliferative profile of compound 1
      and/or its derivatives have been reported up to date. Here, we describe the
      isolation of compound 1 from hexane extract of P. polygalaeflorus fruits as well
      as the semisynthesis of three lactone derivatives: 6 alpha-hydroxyvouacapan-7
      beta,17 beta-lactone (2), 6 alpha-acetoxyvouacapan-7 beta,17 beta-lactone (3),
      and 6-oxovouacapan-7 beta,17 beta-lactone (4). Additionally, antiproliferative
      activity of these compounds against nine human cancer cell lines was
      investigated. Our results revealed that 6 alpha-hydroxyvouacapan-7 beta,17 beta
      lactone (2) was the most potent furanditerpene against all cancer cell lines
      studied. The presence of non-substituted hydroxyl group at C-6 and the presence
      of 7 beta,17 beta-lactone ring are important for the antiproliferative activity
      of these compounds.

PMID- 19394667
TI  - Interindividual differences in o,p'-DDD enantiomer kinetics examined in Gottingen
      minipigs.
AB  - Five minipigs were given a single oral dose of a racemic mixture of o,p'-DDD (30
      mg kg(-1)b.w., EF=0.49). Blood plasma and subcutaneous adipose tissue were
      collected for analysis, at different time-points over 180 d. At the end of the
      experiment also liver, kidney and brain tissue were collected. Low concentrations
      of o,p'-DDD still remained after 180 d in plasma (mean 0.5+/-0.3 ng g(-1)f.w.)
      and in adipose tissue (mean 40+/-40 ng g(-1)f.w.). The mean concentrations in
      liver and kidney were 500+/-300 pg g(-1)f.w. and 90+/-50 pg g(-1)f.w.,
      respectively. The enantiomers of o,p'-DDD were isolated by HPLC and the absolute
      configuration of the enantiomers were determined by X-ray crystallography and
      polarimetry as R-(+)-o,p'-DDD and S-(-)-o,p'-DDD. The enantiomer fractions (EFs)
      of o,p'-DDD were determined in plasma, adipose tissue and kidney using GC/ECD
      equipped with a chiral column. The EFs of o,p'-DDD in the individual minipigs
      showed large variability, ranging from 0.2 to 0.6 after 24h in plasma and from
      0.2 to 0.7 after 90 d in adipose tissue. Hence in two of the minipigs, the S-(-)
      o,p'-DDD enantiomer was dominating while the other enantiomer, R-(+)-o,p'-DDD was
      dominating in three minipigs. We propose that a yet not identified factor related
      to polymorphism, regulating the metabolism and/or elimination of the enantiomeric
      o,p'-DDD, is responsible for the differences in enantiomeric retention of the
      compound in the minipigs.

PMID- 19394668
TI  - Cumulative exposure estimates for polychlorinated biphenyls using a job-exposure
      matrix.
AB  - PCB exposure has been associated with increased risk for cancer, neurological
      disease, and for birth defects in children exposed in utero. Because of the long
      half-lives of PCB congeners, they remain a public health problem in the United
      States 30 years after being banned. Workers (n=3569) at an Indiana capacitor
      manufacturing plant were exposed to polychlorinated biphenyls (PCBs) from 1957 to
      1977. The purpose of this work was to develop a period-specific job-exposure
      matrix (JEM) for a follow-up epidemiologic study investigating the increased
      risks for cancer previously observed in the cohort. METHODS: We used eight
      exposure determinants to estimate PCB exposures systematically. Work history, job
      description, capacitor production factors, PCB usage trends, and air sample data
      were used to develop the JEM in four steps: (1) all job titles (n=884) were
      assessed for exposure determinants, (2) jobs with similar exposure determinants
      were grouped, (3) for each job exposure category, exposure intensity (high-medium
      low-background) and frequency (continuous-intermittent) were qualitatively rated
      separately for inhalation and dermal exposure, and (4) for each job exposure
      category, the product of intensity (based on air sampling data) and frequency
      (fraction of day exposed) was calculated. The JEM was then modified for two eras
      of different PCB exposure conditions. RESULTS: The resulting JEM consists of
      inhalation and dermal exposure values for 19 job exposure categories. CONCLUSION:
      The JEM showed an exposure-response trend associated with increased brain cancer
      mortality in the epidemiologic study.

PMID- 19394669
TI  - Levofloxacin ozonation in water: rate determining process parameters and reaction
      pathway elucidation.
AB  - Ozonation of the quinolone antibiotic levofloxacin was investigated with focus on
      both the levofloxacin degradation rate and degradation product formation.
      Degradation was about 2 times faster at pH 10 compared to pH 3 and 7 explained by
      direct ozonation at the unprotonated N4('), one of the tertiary amines of the
      piperazinyl substituent. H2O2 concentration (2-100 microM) had only limited
      effect. Liquid chromatography - high resolution mass spectrometry revealed
      degradation at the piperazinyl substituent and the quinolone moiety, with the
      relative importance of both pathways being strongly affected by changes in pH.
      Levofloxacin N-oxide concentrations reached up to 40% of the initial levofloxacin
      concentration during ozonation at pH 10. Degradation at the quinolone moiety
      resulted in isatin and anthranilic acid type metabolites, probably formed through
      reaction with hydroxyl radicals. Ab initio molecular orbital calculations
      predicted radical attack mainly at C2 of the quinolone moiety. This is the carbon
      atom with the largest Fukui function. Reaction with ozone is expected to mainly
      occur at N(4)('), characterized by the largest negative charge.

PMID- 19394671
TI  - Temporal trends of polyfluoroalkyl compounds in harbor seals (Phoca vitulina)
      from the German Bight, 1999-2008.
AB  - Temporal trends of polyfluoroalkyl compounds (PFCs) were examined in liver
      samples from harbor seals (Phoca vitulina) collected from the German Bight (1999
      2008). Concentrations of various PFCs, including C(4)-C(10) perfluoroalkyl
      sulfonates (PFSAs), perfluorooctane sulfinate (PFOSi), perfluorooctane
      sulfonamide (FOSA) and C(8)-C(15) perfluoroalkyl carboxylic acids (PFCAs) were
      quantified. Perfluorooctane sulfonate (PFOS) was the predominant compound with a
      maximum concentration of 3676 ng g(-1) ww (1996), making up on average 94% of the
      measured PFCs. Significantly higher concentrations were found in <7 month old in
      comparison to >or=7 month old harbor seals for C(6)-C(8) PFSAs,
      perfluorododecanoic acid (PFDoDA) and FOSA, whereas perfluorodecanoic acid (PFDA)
      showed significantly lower concentrations in the younger harbor seals (p<0.05).
      These results suggest a transplacental transfer of PFCs to the foetus and/or
      consumption of different contaminated food. Regression analysis of logarithmic
      transformed PFC mean concentrations indicated a significant temporal trend with
      decreasing concentrations for C(5)-C(7) PFSAs (p<0.001), PFOSi (p=0.028), FOSA
      (p<0.001) and perfluorooctanoic acid (PFOA) (p=0.031) between 1999 and 2008.
      Furthermore, PFOS decreased by 49% between 1999 and 2008, which correspond with
      decreasing concentration levels of its metabolic precursors PFOSi and FOSA of 83%
      and 95% in the same time period. However, the decreasing trend of PFOS is not
      significant (p=0.067). The reason for the decline during the past 10 years could
      be an effect of the replacement of these PFCs by shorter chained and less
      bioaccumulative compounds. But the observations of increasing perfluorodecane
      sulfonate (PFDS) levels (p=0.070), the high concentrations of PFOS and constant
      levels of C(9)-C(13) PFCAs indicates that further work on the reduction of
      environmental emissions of PFCs are necessary.

PMID- 19394670
TI  - Spatial distribution of polyfluoroalkyl compounds in seawater of the German
      Bight.
AB  - The spatial distribution of polyfluoroalkyl compounds (PFCs) and their
      composition profile was investigated in 48 water samples collected from the
      German Bight. All samples were prepared by solid-phase extraction with Strata XAW
      cartridges and analysed using high performance liquid chromatography/negative
      electrospray ionisation-tandem mass spectrometry (HPLC/(-)ESI-MS/MS).
      Concentrations of various PFCs, including perfluorinated sulfonates (PFSAs),
      perfluorinated carboxylic acids (PFCAs), unsaturated fluorotelomercarboxylic
      acids, perfluoralkyl sulfonamide and sulfonamidoethanol, were quantified. The
      Sigma PFC concentration ranges from 9.36 ng L(-1) to 31.2 ng L(-1), while
      perfluorobutane sulfonate (PFBS, 3.38-17.7 ng L(-1)) and perfluorooctanoic acid
      (PFOA, 2.67-7.83 ng L(-1)) dominated. The rivers Elbe, Weser and Ems had a high
      influence on the distribution of most PFCs in the German Bight, with maximum PFC
      concentrations found in their estuaries, and concentrations decreasing with
      increasing distance from the coast. Conversely, PFBS had its maximum
      concentration not in the estuaries but in the western German Bight, which suggest
      an additional source, where PFBS was transported into the German Bight with the
      westerly current.

PMID- 19394672
TI  - Screening the partition behavior of a large number of chemicals with a quantum
      chemical software.
AB  - For 8500 organic chemicals from the Canadian Domestic Substances List, air/water
      and octanol/water partition coefficients have been calculated with COSMOfrag a
      predictive a priori method based on quantum mechanics and statistical
      thermodynamics provided by COSMOlogic. The results were compared with predictions
      from the EPI Suite. On average a difference of 1.8 log units between both methods
      was observed for the predicted logK(aw) values. This has consequences for the
      classification in terms of atmospheric long range transport potential and
      bioaccumulation in the terrestrial food chain where 11% and 17% of all compounds
      were classified differently. Much better agreement was observed for the predicted
      logK(ow). Principal differences became obvious for compounds that occur as
      isomers or conformers. The modules of the EPI Suite are not designed to account
      for information on stereochemistry of molecules or E/Z isomers. Intramolecular H
      bonds are only accounted for if specific correction factors exist from the
      calibration procedure. In contrast, COSMOfrag in combination with COSMOtherm can
      identify the existence of such isomers or H-bond conformers and account for these
      effects in the calculations.

PMID- 19394673
TI  - PCB and PCDD/F in sediments and mussels of the Istanbul strait (Turkey).
AB  - Sediment and mussel samples collected along the coasts of the Istanbul strait and
      an island in Marmara Sea (Turkey) were analyzed for six indicator polychlorinated
      biphenyl (PCB), 12 dioxin-like PCB (dl-PCB) and 17 polychlorinated dibenzo-p
      dioxin/furan (PCDD/F) congeners. Samples contained different concentrations of
      PCBs and among these, congeners 153, 75, 105 and 118 in sediments and congeners
      153, 138 and 118 in mussels were most abundant. The concentration levels of total
      PCBs and PCDD/Fs in sediments ranged from 17.9 to 539746 pg g(-1)dm and 2.04 to
      60.5 pg g(-1)dm, respectively. The total WHO-TEQ values ranged between 0.01 and
      17.8 pg g(-1)dm in sediments, and 0.98 and 1.01 pg g(-1)ww in mussels. None of
      the sediment and mussel samples analyzed exceeded the limits suggested in the
      sediment quality guideline and safe values set by the European Community for
      seafood intended for human consumption, respectively.

PMID- 19394674
TI  - Effects of cypermethrin chronic exposure and water temperature on survival,
      growth, sex differentiation, and gonadal developmental stages of Odontesthes
      bonariensis (Teleostei).
AB  - This study assessed the effects of cypermethrin and temperature on the survival,
      growth, sex differentiation, and gonadal development of Odontesthes bonariensis,
      a gonochoristic teleost with a strong thermolabile sex differentiation. Two
      complementary trials were conducted. In the first trial, newly hatched larvae
      were exposed during six weeks to 0 or 0.1 microgL(-1) of cypermethrin at 17, 22,
      and 29 degrees C. In the second trial, larvae were exposed at 22 degrees C to 0,
      0.1, or 0.125 microgL(-1) of cypermethrin, or 100 microgL(-1) of the non
      steroidal antiestrogen tamoxifen. Survival and growth of fish were affected by
      cypermethrin exposure, water temperature, and the combination of both factors.
      The survival rate decreased at higher temperatures and cypermethrin
      concentrations, but the insecticide lethality was inversely related to
      temperature. Growth was lower at 17 degrees C than at 22 or 29 degrees C, and was
      significantly increased by cypermethrin exposure. As already described for this
      species, all females or all males were obtained at 17 or 29 degrees C,
      respectively, and neither cypermethrin nor tamoxifen exposure caused changes in
      sex ratios. Slight changes in gonadal development were induced only by
      temperature. Finally, results showed that the in vitro antiestrogenic effect
      reported for cypermethrin had no in vivo effects on the sex ratio, the gonadal
      development, or the germ cell production of O. bonariensis, even at
      concentrations that affected the growth and survival of the fish.

PMID- 19394675
TI  - Fluoride toxicity effects in onion (Allium cepa L.) grown in contaminated soils.
AB  - A pot experiment was carried out under controlled condition to investigate the
      accumulation, uptake and toxicity effects of fluoride (F) in onion (Allium cepa
      L.) grown on the soil contaminated by inorganic fluoride (NaF). Six different
      levels of soil contamination were used by adding 0, 100, 200, 400, 600 and 800 mg
      NaFkg(-1) to the soil. The F concentration in shoot, bulb and root varied between
      16.3 and 109.1mg Fkg(-1), 15.8 and 54.3mg Fkg(-1) and 18.6 and 151.6 mg Fkg(-1),
      respectively. The visible symptoms of F toxicity in terms of tip burning and
      death of the plant was noticed in highly contaminated soils (>400mg NaFkg(-1)
      soil). The phyto-toxic threshold limit (LC(50)) in onion shoot was found to be 55
      mg Fkg(-1), beyond which the biomass yield decreased by 50%. It was also inferred
      from the study that there is a partitioning of F in onion, with more accumulation
      in roots and shoots than in bulbs. The order of retention of fluoride in onion
      found to be roots>shoot>bulb.

PMID- 19394676
TI  - Peat fires and air quality: volatile organic compounds and particulates.
AB  - There are numerous localized peat deposits on the Swan Coastal Plain, an urban
      and rural bioregion otherwise dominated by wetland ecosystems in southwestern
      Australia. Hydrological change is significant in the bioregion: urban development
      encroaches on wetlands, groundwater extraction provides the city population with
      most of its water, and rainfall declines will not recharge aquifers in the
      future. The wetland processes which contribute to the formation of these peat
      deposits have therefore changed and are becoming vulnerable to fire events with
      residents increasingly exposed to peat smoke. There is an imperative to
      characterise this peat smoke to determine if exposures are harmful or toxic, and
      opportunities to do so in this setting arise due to the absence of bushfire smoke
      which has confounded other international studies. We have measured volatile
      organic compounds (VOCs) and particulate concentrations from an opportunistic
      assessment of two peat fires. SUMMA canister grab samples and a portable GCMS
      were used to determine the VOCs with high 1h benzene concentrations of 16 and 30
      ppm v/v. PM10 and PM2.5 particulate data were collected using an Osiris
      continuous analyser with 24h concentrations recorded at varying time periods
      (within a 5 months timeframe) ranging from 1h maximums of between 23-37 microgm(
      3) for PM10 and 50.5-106 microgm(-3) for PM2.5. While the 24h averages were
      generally below national air quality standards, elevated 1h concentrations were
      observed on numerous occasions and on most days. Given the proximity of
      residential development to many peat deposits, a drying climate and the increased
      risk of arson in peri-urban environments, the health impacts of exposure to peat
      smoke need to be determined and if necessary measures developed to prevent
      exposure (which would include maintaining wetland sediment integrity so as to
      reduce its vulnerability to fire).

PMID- 19394677
TI  - Occurrence and pathways of manure-borne 17beta-estradiol in vadose zone water.
AB  - The hormone 17beta-estradiol (E2) can cause endocrine disruption in sensitive
      species at part per trillion concentrations. The persistence and transport
      pathways of manure-borne E2 in agricultural soils were determined by comparing
      its occurrence with the transfer of water and the transport of non-sorbing
      fluorobenzoic acid (FBA) tracers. This comparison was done using capillary wick
      lysimeters installed 0.61m beneath three corn (Zea mays L.) plots that receive
      swine (Sus scrofa domesticus) manure from various sources. An additional control
      plot was included that received no manure. Soil water transfer was modeled to
      compare actual versus predicted percolation. On average, lysimeters collected 61%
      of the expected percolation and 8% of the FBA. There were frequent E2 detections,
      where there were an average of 8 detections for the 11 sample events. The average
      detection was 21ngL(-1) and its range was 1-245ngL(-1). 17beta-Estradiol was
      detected before manure was applied and also in the control plot lysimeters.
      Furthermore, the average mass recovery of E2 in all the lysimeters was >50%,
      which was greater than the FBA tracer recovery. Results indicated that tracer was
      transported with precipitated water infiltrating into the soil surface and
      percolating down through the soil profile. There was substantial evidence for
      antecedent E2, which was persistent and mobile. The persistence and mobility of
      the E2 may result from its associations with colloids, such as dissolved organic
      matter. Furthermore, this antecedent E2 appeared to overwhelm any observable
      effect of manure management on E2 fate and transport.

PMID- 19394678
TI  - Estimation of 210Po and its risk to human beings due to consumption of marine
      species at Mumbai, India.
AB  - (210)Po was estimated in the edible muscle and soft tissue of 15 different marine
      species (fish, crab, prawn and bivalve) collected from Trans-Thane Creek area
      (Trombay) and Thane. Potential risks associated with consumption of marine
      organisms due to (210)Po collected from this particular area to human beings were
      assessed. Estimation of (210)Po was carried out using radiochemical separation
      and alpha spectrometric technique. The concentration of (210)Po was found to vary
      from 0.18 to 10.9 Bqkg(-1) wet wt in different biota species and maximum
      concentrations were observed in bivalves. The variations in (210)Po concentration
      in different species are mainly due to difference in metabolism and feeding
      habits. The daily intake and individual dose of (210)Po to human beings through
      biota consumption was calculated and found to be 31.89 mBqd(-1) and 19.44
      microSvyr(-1), respectively. An assessment of the risk on human beings due to
      consumption of marine organism was undertaken using carcinogenic slope factor for
      (210)Po. 5th, 50th and 95th percentile of life time risk was calculated to be
      9.74E-06, 4.39E-05 and 2.12E-04, respectively.

PMID- 19394679
TI  - Homeothermy and primate bipedalism: is water shortage or solar radiation the main
      threat to baboon (Papio hamadryas) homeothermy?
AB  - Other than the hominin lineage, baboons are the diurnally active primates that
      have colonized the arid plains of Africa most successfully. While the hominin
      lineage adopted bipedalism before colonizing the open, dry plains, baboons
      retained a quadrupedal mode of locomotion. Because bipedalism has been considered
      to reduce the thermoregulatory stress of inhabiting open dry plains, we
      investigated how baboons cope with thermal loads and water restriction. Using
      implanted data loggers, we measured abdominal temperature every 5 min in six
      unrestrained baboons while they were exposed to simulated desert conditions (15
      degrees C at night rising to 35 degrees C during the day, with and without extra
      radiant heating), or an ambient temperature of 22 degrees C. At 22 degrees C,
      core temperature averaged 37.9 degrees C and cycled nychthemerally by 1.7 degrees
      C. Mean, minimum, and maximum daily core temperatures in euhydrated baboons in
      the simulated desert environments did not differ from the temperatures displayed
      in the 22 degrees C environment, even when radiant heating was applied. At 22
      degrees C, restricting water intake did not affect core temperature. During the
      desert simulations, maximum core temperature increased significantly on each day
      of water deprivation, with the highest temperatures (>40 degrees C) on the third
      day in the simulation that included radiant heat. When drinking water heated to
      38 degrees C was returned, core temperature decreased rapidly to a level lower
      than normal for that time of day. We conclude that baboons with access to water
      can maintain homeothermy in the face of high air temperatures and radiant heat
      loads, but that a lack of access to drinking water poses a major threat to baboon
      homeothermy. We speculate that any competitive thermoregulatory advantage of
      bipedalism in early hominins was related to coping with water shortage in hot
      environments, and that their freed hands might have enabled them to transport
      enough water to avoid dangerous hyperthermia.

PMID- 19394680
TI  - Pharmaceutical and personal care products in tile drainage following surface
      spreading and injection of dewatered municipal biosolids to an agricultural
      field.
AB  - Land application of municipal biosolids can be a source of environmental
      contamination by pharmaceutical and personal care products (PPCPs). This study
      examined PPCP concentrations/temporally discrete mass loads in agricultural tile
      drainage systems where two applications of biosolids had previously taken place.
      The field plots received liquid municipal biosolids (LMB) in the fall of 2005 at
      an application rate of approximately 93,500 L ha (-1), and a second land
      application was conducted using dewatered municipal biosolids (DMB) applied at a
      rate of approximately 8Mg dw ha (-1) in the summer of 2006 [corrected].The DMB
      land application treatments consisted of direct injection (DI) of the DMB beneath
      the soil surface at a nominal depth of approximately 0.11 m, and surface
      spreading (SS) plus subsequent tillage incorporation of DMB in the topsoil
      (approximately 0.10 m depth). The PPCPs examined included eight pharmaceuticals
      (acetaminophen, fluoxetine, ibuprofen, gemfibrozil, naproxen, carbamazepine,
      atenolol, sulfamethoxazole), the nicotine metabolite cotinine, and two
      antibacterial personal care products triclosan and triclocarban. Residues of
      naproxen, cotinine, atenolol and triclosan originating from the fall 2005 LMB
      application were detected in tile water nearly nine months after application
      (triclocarban was not measured in 2005). There were no significant differences
      (p>0.05) in PPCP mass loads among the two DMB land application treatments (i.e.,
      SS vs. DI); although, average PPCP mass loads late in the study season (>100 days
      after application) were consistently higher for the DI treatment relative to the
      SS treatment. While the concentration of triclosan (approximately 14,000 ng g(-1)
      dw) in DMB was about twice that of triclocarban (approximately 8000 ng g(-1) dw),
      the average tile water concentrations for triclosan were much higher (43+/-5 ng
      L(-1)) than they were for triclocarban (0.73+/-0.14 ng L(-1)). Triclosan
      concentrations (maximum observed in 2006 approximately 235 ng L(-1)) in tile
      water resulting from land applications may warrant attention from a toxicological
      perspective.

PMID- 19394681
TI  - Clinical usefulness of prothrombin fragment 1+2 in patients with suspected
      pulmonary embolism.

PMID- 19394683
TI  - Gain of 3q26: a genetic marker in low-grade squamous intraepithelial lesions
      (LSIL) of the uterine cervix.
AB  - OBJECTIVE: Physicians have few resources for determining which LSIL will progress
      to HSIL or regress. Recently the chromosome 3q26 region was found to be amplified
      in patients with cervical cancer. The frequency of this 3q gain increased with
      severity of dysplasia. The primary objective of this study was to evaluate an
      automated FISH assay for detection of 3q gain in liquid cytology samples as a
      potential tool for risk stratification and triaging. METHODS: Slides prepared
      from 257 liquid cytology specimens (97 Negative, 135 LSIL 25 HSIL) were
      hybridized with a single-copy probe for the chromosome 3q26 region and a probe
      for the centromeric alpha-repeat sequence of chromosome 7, using standard FISH
      methods. Using automated analysis, the total number of nuclei and the number of
      nuclei with >2 signals for 3q26 were determined, using a 20x objective. The
      nuclei were rank ordered based on number of 3q26 FISH signals. The 800 nuclei
      with the highest number of signals were scored using both FISH probes and nuclei
      with increased numbers of 3q signals were enumerated. RESULTS AND CONCLUSIONS:
      Analysis of 257 specimens demonstrated that a fully automated FISH scoring system
      can detect 3q gain in liquid cytology samples. A fully automated method for
      determination of 3q gain in liquid cytology may be the assay necessary to
      implement routine testing. Additional studies to validate the utility of this
      technology are needed.

PMID- 19394685
TI  - Cartilage-hair hypoplasia and severe allergy.

PMID- 19394686
TI  - Treatments for nicotine addiction should be a top priority.

PMID- 19394687
TI  - Differential proteomics analysis of the surface heterogeneity of dextran iron
      oxide nanoparticles and the implications for their in vivo clearance.
AB  - In order to understand the role of plasma proteins in the rapid liver clearance
      of dextran-coated superparamagnetic iron oxide (SPIO) in vivo, we analyzed the
      full repertoire of SPIO-binding blood proteins using novel two-dimensional
      differential mass spectrometry approach. The identified proteins showed
      specificity for surface domains of the nanoparticles: mannan-binding lectins
      bound to the dextran coating, histidine-rich glycoprotein and kininogen bound to
      the iron oxide part, and the complement lectin and contact clotting factors were
      secondary binders. Nanoparticle clearance studies in knockout mice suggested that
      these proteins, as well as several previously identified opsonins, do not play a
      significant role in the SPIO clearance. However, both the dextran coat and the
      iron oxide core remained accessible to specific probes after incubation of SPIO
      in plasma, suggesting that the nanoparticle surface could be available for
      recognition by macrophages, regardless of protein coating. These data provide
      guidance to rational design of bioinert, long-circulating nanoparticles.

PMID- 19394688
TI  - Biocompatibility of injectable chitosan-phospholipid implant systems.
AB  - Injectable biomaterials are desirable therapeutic platforms due to minimal
      invasiveness and improved patient compliance, and are applicable in such areas as
      compound delivery and tissue engineering. The present work examined the
      biocompatibility of injectable blends composed of chitosan, phospholipid and
      lauric aldehyde (PoLi(gel)-LA) or lauric chloride (PoLi(gel)-LCl). In vitro
      cytotoxicity was evaluated in L929 and HeLa cell lines. Both blends resulted in
      acceptable biocompatibility, although greater cell viability was seen with
      PoLi(gel)-LA. In vivo biocompatibility was investigated in healthy CD-1 mice.
      Subcutaneous injection of the PoLi(gel)-LA blend caused no local or systemic
      toxicities over a four-week period while the PoLi(gel)-LCl caused immediate local
      toxicity. Mice injected intraperitoneally with PoLi(gel)-LA did not show physical
      or behavioural alterations, and body weight changes did not differ from control
      animals. Furthermore, histological examination of spleen and liver showed
      unaltered morphology. Interleukin-6 levels in mice injected with PoLi(gel)-LA did
      not differ from levels of control animals (6.91+/-3.61 pg/mL versus 6.92+/-5.02
      pg/mL, respectively). Biodegradation occurred progressively, with 7.4+/-5.02% of
      the original injected mass remaining after four weeks. Results obtained herein
      establish the biocompatibility of PoLi(gel)-LA and indicate its potential for use
      in various localized therapeutic applications.

PMID- 19394689
TI  - The relationship between the antimicrobial effect of catheter coatings containing
      silver nanoparticles and the coagulation of contacting blood.
AB  - It is well known that surface coatings for medical devices can be made
      antimicrobial through introduction of silver nanoparticles. By virtue of their
      extremely large surface-to-volume ratio, the silver particles serve as a depot
      for sustained release of silver ions, despite the fact that silver is not readily
      oxidized. Antimicrobial coatings are especially important in connection with
      indwelling catheters with a high risk of bacterial line infections, such as
      central venous catheters (CVCs). This study specifically addressed the question
      what the impact of silver nanoparticles (exposed at the coating's surface) and/or
      the release of silver ions would be on coagulation of contacting blood. Studies,
      performed in vitro with fresh platelet-rich blood plasma (PRP) from 5 different
      healthy volunteer donors, clearly pointed out that: (i) the presence of silver
      nanoparticles correlates with accelerated thrombin formation upon contact of the
      coating with PRP; (ii) platelet activation is stronger as a result from the
      contact with silver nanoparticle-containing coatings as compared to other
      coatings which are devoid of silver. A series of titration experiments, in which
      the potential effect of silver ions is mimicked, revealed that the observed
      activation of blood platelets can be best explained through a collision
      mechanism. The results suggest that platelets that collide with silver, exposed
      at the surface, become activated without adhering to the surface. These new
      results point, rather unexpectedly, at a double effect of the silver
      nanoparticles in the coating: a strong antimicrobial effect occurs simultaneously
      with acceleration of the coagulation of contacting blood. This new information
      is, evidently, most relevant for the development of improved surface coatings for
      indwelling catheters (such as CVCs) which should combine antimicrobial features
      and close-to-zero thrombogenicity.

PMID- 19394690
TI  - In vitro characterization of the effects of rat/mouse hemokinin-1 on mouse
      colonic contractile activity: a comparison with substance P.
AB  - Rat/mouse hemokinin-1 (r/m HK-1) has been identified as a member of the
      tachykinin family and its effect in colonic contractile activity remains unknown.
      We investigated the effects and mechanisms of actions of r/m HK-1 on the mouse
      colonic contractile activity in vitro by comparing it with that of substance P
      (SP). R/m HK-1 induced substantial contractions on the circular muscle of mouse
      colon. The maximal contractile responses to r/m HK-1 varied significantly among
      proximal-, mid- and distal-colon, suggesting that the action of r/m HK-1 was
      region-specific in mouse colon. The contractile response induced by r/m HK-1 is
      primarily via activation of tachykinin NK(1) receptors leading to activation of
      cholinergic excitatory pathways and with a minor contribution of NK(2) receptors,
      which may be on the smooth muscle itself. A direct action on colonic smooth
      muscles may be also involved. In contrast, SP induced biphasic colonic responses
      (contractile and relaxant responses) on the circular muscle, in which the
      contractile action of SP was equieffective with r/m HK-1. SP exerted its
      contractile effect predominantly through neural and muscular tachykinin NK(1)
      receptors, but unlike r/m HK-1 did not appear to act via NK(2) receptors. The
      relaxation induced by SP was largely due to release of nitric oxide (NO) produced
      via an action on neural NK(1) receptors. These results indicate that the
      receptors and the activation properties involved in r/m HK-1-induced mouse
      colonic contractile activity are different from those of SP.

PMID- 19394691
TI  - GCP, a genistein-rich compound, inhibits proliferation and induces apoptosis in
      lymphoma cell lines.
AB  - Genistein combined polysaccharide (GCP), derived from soy bean extract, is
      comprised of deglycosylated isoflavones, such as genistein and daidzein. The goal
      of this work was to determine if GCP is effective in lymphoid cancers. In three
      human and four canine lymphoid cell lines, GCP inhibited proliferation and
      induced G2/M arrest. Additionally, increased apoptosis was observed in Ramos and
      Jurkat lines. These results demonstrate that GCP is effective in lymphoid cell
      lines of both human and canine origin. Due to its minimal toxicities, increased
      bioavailability, and in vitro efficacy, GCP may have clinical utility in the
      treatment of patients with lymphoma.

PMID- 19394692
TI  - ZD6474 inhibits Src kinase leading to apoptosis of imatinib-resistant K562 cells.
AB  - ZD6474 is an orally available, small-molecule tyrosine kinase inhibitor. This
      study explores the effect of ZD6474 on imatinib-resistant K562 cell lines, which
      show markedly increased SRC family kinases (SFKs) activity. ZD6474 induces growth
      arrest and apoptosis of imatinib-resistant and parental K562 cells, as well as
      inhibition of Src activity and its downstream effectors, the anti-apoptotic Bcl-2
      family. ZD6474 treatment also inhibits the activity of STAT3 and reactivation of
      its activity results in suppression of the anti-tumor effects of SFKs inhibitors.
      A single oral administration of ZD6474 produced dose-dependent inhibition of
      imatinib-resistant K562 cells xenograft tumors. These results suggest that
      clinical assessment of ZD6474 against imatinib-resistant CML is warranted.

PMID- 19394693
TI  - Myeloproliferative disorder with eosinophilia and ETV6-ABL gene rearrangement:
      efficacy of second-generation tyrosine kinase inhibitors.
AB  - ETV6/ABL is a rare gene rearrangement that has rarely been detected in
      Philadelphia-negative chronic myeloproliferative disorders (C-MPD) and found to
      have tyrosine kinase activity similar to the BCR/ABL fusion protein. We describe
      a case of a 61-year-old female with a C-MPD associated with an ETV6/ABL gene
      rearrangement. She achieved complete cytogenetic remission on imatinib 400mg
      daily for 17 months, but then developed morphologic and cytogenetic relapse.
      After starting nilotinib 400mg orally twice daily, she achieved CCyR at 3, 6, and
      11 months, suggesting that second-generation TKIs can result in favorable
      responses in patients with ETV6/ABL rearrangement who relapse after imatinib.

PMID- 19394694
TI  - Application of metamorphosis assay to a native Japanese amphibian species, Rana
      rugosa, for assessing effects of thyroid system affecting chemicals.
AB  - The aims of this study were to assess the utility of a metamorphosis assay for
      detecting thyroid hormone-disrupting chemicals using Rana rugosa, a domestic frog
      species in Japan, and to compare species differences in sensitivity to thyroxine
      (T(4)) and propylthiouracil (PTU) among R. rugosa, Xenopus laevis and Xenopus
      (Silurana) tropicalis. Tadpoles of R. rugosa (TK stages III/IV) were exposed to
      standard test chemicals for acceleration (T(4)) and inhibition (PTU) of
      metamorphosis for 28 days in semi-static condition and total body length and
      developmental stage (TK stage) were recorded every week. T(4) (0.61 and 2.24
      microg/L in actual concentrations) and PTU (19.73, 76.83, and 155.67 mg/L in
      actual concentrations) induced significant acceleration and inhibition of
      metamorphosis, respectively. The present results indicate that the metamorphosis
      assay is successfully applied to the domestic frog species, R. rugosa, suggesting
      this assay can be used for the assessment of chemicals on ecological impacts in
      wild frog species.

PMID- 19394695
TI  - Multiple focal nodular hyperplasia of the liver associated with spinal and
      pulmonary arteriovenous malformations.
AB  - Focal nodular hyperplasia (FNH) is frequently found incidentally in liver imaging
      but multiple FNH, especially when associated with systemic vascular
      malformations, are rare. We report on the case of a patient with lumbar
      sciatalgia and paraparesis. Spinal magnetic resonance angiography (MRA) showed a
      spinal cord arteriovenous shunt (SCAVS), its arterial feeders and venous
      drainage, which were later confirmed by digital subtraction angiography (DSA).
      MRA of the spine offers promising results in the characterization of SCAVS.
      Thoracoabdominal CT and MRI revealed multiple hepatic FNH and a pulmonary
      arteriovenous malformation (AVM). Indeed, this is the first reported case of the
      rare multiple FNH syndrome associated with a spinal AVM.

PMID- 19394696
TI  - [Two particular cases of superior semicircular canal dehiscence related to a
      procidence of the superior petrous sinus].
AB  - We report two cases of superior semicircular canal dehiscence related to a
      dehiscence of the superior petrous sinus that creates a localized notch of the
      most superior part of the superior semicircular canal. This vascular dehiscence
      was suspected at CT and was confirmed by MR imaging with identification of the
      superior petrous sinus in touch with the intralabyrinthine fluid at this level.
      This not well-known etiology of the superior semicircular canal dehiscence
      syndrome has to be searched and described by radiologists, allowing an optimal
      surgical approach.

PMID- 19394698
TI  - An amphioxus TLR with dynamic embryonic expression pattern responses to pathogens
      and activates NF-kappaB pathway via MyD88.
AB  - A big bang expansion of the Vertebrate-type (V-type) TLRs was reported in
      amphioxus. To shed lights on its implications, a unique TLR which is reversely
      inserted into an intron of amphioxus PSMB7-10 by retrotransposition in the highly
      polymorphic proto-MHC region was cloned from Chinese amphioxus (Branchiostoma
      belcheri tsingtauense) and named as bbtTLR1. In situ assays showed that bbtTLR1
      was predominantly expressed in pharynx and gut from larva to adult stages, which
      are considered as the first frontlines of amphioxus defense system. Acute immune
      challenges revealed that the expression of bbtTLR1 was stimulated by bacteria and
      their cell wall components, while suppressed by Glucan and Poly I:C in the
      digestive system. Amphioxus also had dozens of TIR adaptors from which we cloned
      bbtMyD88. BbtMyD88 expressed in 293T cells led to the activation of NF-kappaB
      pathway through its DEATH and middle domains. Moreover, this activation could be
      enhanced by bbtTLR1 through the direct association with bbtMyD88. In summary,
      this study provides evidence for the immune-relation of amphioxus V-type TLRs,
      and suggests that amphioxus TLR1 and MyD88 represent a basic evolutionary
      pathway.

PMID- 19394697
TI  - Early wheezing phenotypes and severity of respiratory illness in very early
      childhood: study on intrauterine exposure to fine particle matter.
AB  - The main goal of the paper was to assess the pattern of risk factors having an
      impact on the onset of early wheezing phenotypes in the birth cohort of 468 two
      year olds and to investigate the severity of respiratory illness in the two-year
      olds in relation to both wheezing phenotypes, environmental tobacco smoke (ETS)
      and personal PM(2.5) exposure over pregnancy period (fine particulate matter).
      The secondary goal of the paper was to assess possible association of early
      persistent wheezing with the length of the baby at birth. Pregnant women were
      recruited from ambulatory prenatal clinics in the first and second trimester of
      pregnancy. Only women 18-35 years of age, who claimed to be non-smokers, with
      singleton pregnancies, without illicit drug use and HIV infection, free from
      chronic diseases were eligible for the study. In the statistical analysis of
      respiratory health of children multinomial logistic regression and zero-inflated
      Poisson regression models were used. Approximately one third of the children in
      the study sample experienced wheezing in the first 2 years of life and in about
      two third of cases (67%) the symptom developed already in the first year of life.
      The early wheezing was easily reversible and in about 70% of infants with
      wheezing the symptom receded in the second year of life. The adjusted relative
      risk ratio (RRR) of persistent wheezing increased with maternal atopy (RRR=3.05;
      95%CI: 1.30-7.15), older siblings (RRR=3.05; 95%CI: 1.67-5.58) and prenatal ETS
      exposure (RRR=1.13; 95%CI: 1.04-1.23), but was inversely associated with the
      length of baby at birth (RRR=0.88; 95%CI: 0.76-1.01). The adjusted incidence risk
      ratios (IRR) of coughing, difficult breathing, runny/stuffy nose and
      pharyngitis/tonsillitis in wheezers were much higher than that observed among non
      wheezers and significantly depended on prenatal PM(2.5) exposure, older siblings
      and maternal atopy. The study shows a clear inverse association between maternal
      age or maternal education and respiratory illnesses and calls for more research
      efforts aiming at the explanation of factors hidden behind proxy measures of
      quality of maternal care of babies. The data support the hypothesis that burden
      of respiratory symptoms in early childhood and possibly in later life may be
      programmed already in prenatal period when the respiratory system is completing
      its growth and maturation.

PMID- 19394699
TI  - Demethylating treatment suppresses natural killer cell cytolytic activity.
AB  - NK cells as a component of the innate immune system provide a first line of
      defense against viral infections and malignancies. Killer immunoglobulin-like
      receptors (KIRs) are a polymorphic gene family expressed on NK cells. The crucial
      role of DNA methylation in determining the variegated expression pattern of KIRs
      has recently been reported. In this study the direct effect of DNA demethylating
      treatment on human NK cell cytotoxicity was analyzed. In a human NK cell line NK
      92MI, inhibitory KIR genes exhibited characteristic epigenetic repression, whose
      promoter regions are densely methylated. Treatment of NK-92MI cells with
      methyltransferase inhibitor 5-azacytidine significantly increased the expression
      levels of inhibitory KIRs and strongly suppressed their cytolytic activity
      against human K562 leukemic cells. Cytolytic activity of human polyclonal NK
      cells was also suppressed upon 5-azacytidine-treatment. The suppression of NK
      cell cytotoxicity was associated with 5-azacytidine-induced overexpression of
      inhibitory KIRs and impaired granzyme B and perforin release by these cells. The
      results demonstrate for the first time that demethylating treatment can suppress
      NK cell cytolytic activity. The aberrant methylation patterns of KIR genes during
      NK cell differentiation and maturation may have importance for its abnormal
      function.

PMID- 19394700
TI  - In vivo laser confocal microscopy findings and mutational analysis for Schnyder's
      crystalline corneal dystrophy.
AB  - OBJECTIVE: To identify any mutation of the UbiA prenyltransferase domain
      containing protein 1 (UBIAD1) gene in Japanese patients with Schnyder's
      crystalline corneal dystrophy (SCCD) and to investigate in vivo microstructural
      phenotype and genotype correlations using laser scanning confocal microscopy
      (Heidelberg Retina Tomograph 2 Rostock Cornea Module; Heidelberg Engineering
      GmbH, Dossenheim, Germany). DESIGN: Small, comparative case series. PARTICIPANTS:
      Three patients from 3 pedigrees (3 males) with clinically diagnosed SCCD and
      their relatives (2 males, 1 female) participated in this study. TESTING: All
      participants were examined genetically and by slit-lamp biomicroscopy and in vivo
      laser confocal microscopy. MAIN OUTCOME MEASURES: Genomic DNA from the patients
      and 100 unrelated healthy volunteers (200 chromosomes) was isolated from blood
      samples and used for mutation screening of the UBIAD1 gene. Selected confocal
      images of corneal layers were evaluated qualitatively for shape and degree of
      light reflection of deposits. RESULTS: Novel mutations in the UBIAD1 gene (Y174C,
      K181R, and N233H) were identified. Additionally, cosegregation of the mutation
      (Y174C) and SCCD was confirmed in 1 pedigree, indicating that the mutation of the
      UBIAD1 gene is causative for SCCD. The 3 mutations were absent in all 200 control
      chromosomes. In vivo laser confocal microscopy demonstrated subepithelial highly
      reflective crystals in 4 cases; the shapes of the crystals were needle-shaped (3
      cases) or rectangular (1 case). A phenotype and genotype correlation was
      demonstrated in 1 pedigree, and phenotypic heterogeneity (SCCD with or without
      crystals caused by a same mutation of Y174C in the UBIAD1 gene) also was
      demonstrated in 1 pedigree. CONCLUSIONS: Nonsynonymous novel mutations in the
      UBIAD1 gene were detected in 3 unrelated Japanese pedigrees with SCCD, confirming
      the genetic heterogeneity of this disorder. In vivo laser confocal microscopy is
      capable of identifying characteristic corneal microstructural changes related to
      genetically mapped SCCD with high resolution, and phenotypic heterogeneity was
      presented. Further confocal and mutational analysis using a larger number of
      patients with SCCD is required to elucidate in vivo microstructural phenotype and
      genotype correlations. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary
      or commercial interest in any materials discussed in this article.

PMID- 19394701
TI  - Characterization of the corneal surface in limbal stem cell deficiency and after
      transplantation of cultivated limbal epithelium.
AB  - PURPOSE: Transplantation of in vitro-cultivated limbal epithelium (TCLE) recently
      was developed to treat limbal stem cell deficiency (LSCD). The objective of this
      study was to characterize changes in the cornea during LSCD and on the corneal
      surface after TCLE. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: The
      pannus tissue excised from the corneas of 17 LSCD patients was analyzed to
      characterize the changes in the cornea during LSCD. Five corneal buttons obtained
      during perforating keratoplasty (pKP) from patients who had undergone TCLE at
      least 6 months before pKP were examined to assess the effect of TCLE. Six samples
      of healthy central cornea and 6 of bulbar conjunctiva served as control tissue.
      METHODS: The expression of epithelial lineage markers (keratin [K] 3, K12, K19,
      and mucin 5AC) and inflammatory markers (interleukin-1alpha [IL-1alpha], IL
      1beta, intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion
      molecule 1 [VCAM-1], and vascular endothelial growth factor [VEGF]) were analyzed
      using real-time polymerase chain reaction, Western blotting, and
      immunofluorescence in the tissue samples. MAIN OUTCOME MEASURES: Comparison of
      the markers' expression patterns. RESULTS: The expression of all markers differed
      in healthy cornea and conjunctiva. Expression of lineage markers was similar in
      pannus to conjunctiva, but not to cornea. Interleukin-1beta, ICAM-1, VCAM-1, and
      VEGF were increased significantly in pannus compared with the levels in healthy
      cornea. Interleukin-1alpha, IL-1beta, and ICAM-1 were increased compared with
      healthy conjunctiva. The TCLE improved vision and reduced inflammation,
      vascularization, and discomfort. After TCLE, the lineage markers in the excised
      corneal buttons showed a corneal phenotype and a significant reduction in
      inflammatory markers in 4 of 5 cases. CONCLUSIONS: Limbal stem cell deficiency is
      characterized by ingrowth of abnormal inflamed tissue with a conjunctival
      phenotype. Transplantation of limbal epithelium cultivated in vitro on intact
      amniotic membrane restored a noninflamed ocular surface and a corneal phenotype.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 19394702
TI  - In vivo confocal microscopic findings of corneal wound healing after corneal
      epithelial debridement in diabetic vitrectomy.
AB  - PURPOSE: To study healing of corneal wounds using in vivo confocal microscopy in
      patients who received corneal epithelial debridement during pars plana vitrectomy
      for proliferative diabetic retinopathy and to investigate risk factors for
      delayed healing. DESIGN: Prospective, observational case series. PARTICIPANTS:
      Forty-four eyes of 40 patients were enrolled. METHODS: In vivo confocal
      microscopy was used to evaluate selected images of the corneal basal and apical
      surface epithelial cells and subbasal nerves before surgery, weekly for the first
      month, and at 3 and 6 months after surgery. Slit-lamp biomicroscopy was carried
      out at the same time. Multiple linear regression analysis of selected potential
      risk factors was performed to investigate the main determinants of delayed
      corneal healing. MAIN OUTCOME MEASURES: Healing rate of corneal epithelial cells
      and subbasal nerves and factors influencing the healing. RESULTS: By slit-lamp
      biomicroscopy, corneal epithelial defects were found in 22.8% of eyes at 2 weeks
      and in 5.4% at 1 month after surgery. In vivo confocal microscopy demonstrated
      incomplete healing of basal epithelial cells in 72.1%, 15.2%, and 0% of eyes and
      incomplete healing of surface apical epithelial cells in 81.1%, 9.1%, and 0% of
      eyes at 1, 3, and 6 months after surgery. The percentage of subbasal nerves
      regaining preoperative appearance was 0%, 6.8%, and 89.3% at 1, 3, and 6 months
      after surgery. Regression analysis revealed infusion of silicone oil (P = 0.020)
      and C(3)F(8) (P = 0.017) resulted in delayed healing by slit-lamp biomicroscopy;
      age (P = 0.028), diabetic treatment regimen (P = 0.014), and scleral buckling (P
      = 0.001) correlated with delayed recovery of basal cells by in vivo confocal
      microscopy. The latter 2 factors also were related to delayed reconformation of
      apical cells (P = 0.011 and 0.004, respectively). Neither healing of apical and
      basal cells showed a significant correlation to findings by slit-lamp
      biomicroscopy (r = 0.19 and 0.09). CONCLUSIONS: Healing of corneal epithelial
      wounds in diabetic eyes is slow. Both the basal and apical epithelial layers were
      involved in the slow healing process. Age, diabetic treatment regimen, and
      several intraoperative factors may alter healing rates. FINANCIAL DISCLOSURE(S):
      The author(s) have no proprietary or commercial interest in any materials
      discussed in this article.

PMID- 19394703
TI  - Risk factors for recurrence after Staphylococcus aureus bacteraemia. A
      retrospective matched case-control study.
AB  - OBJECTIVES: We sought to identify risk factors for recurrence of Staphylococcus
      aureus bacteraemia (SAB) by auditing compliance with guidelines on its treatment
      in our hospital. METHODS: We retrospectively identified patients over the
      preceding 8 years whose SAB had recurred, matching each to a control patient with
      non-recurrent SAB. RESULTS: 40/1870 patients with SAB had suffered recurrent
      disease (2.1%), 33 of whom were available for study. Where 2, 4 and 6 weeks of
      intravenous therapy were recommended, 78%, 29% and 25% of patients received it,
      and there was no association with recurrence. Glycopeptide use in patients with
      methicillin sensitive SAB (MSSA) was significantly associated with recurrence
      (p=0.015). Where the source of the bacteraemia was a peripheral venous catheter
      the odds of recurrence were less than where an SAB originated at another site
      (p=0.047). All patients with SAB in whom a central venous catheter was not
      removed suffered recurrence. CONCLUSIONS: We found the recurrence rate after SAB
      was low despite poor compliance with guidelines on treatment duration.
      Glycopeptide therapy for MSSA bacteraemia was more likely to result in recurrent
      SAB than beta-lactam therapy. Recurrence was significantly less likely in
      patients where the source of the SAB was a peripheral line than in those with
      another source.

PMID- 19394704
TI  - Recurrent Clostridium difficile infection: a review of risk factors, treatments,
      and outcomes.
AB  - Episodes of recurrent Clostridium difficile infection (CDI) are difficult to
      treat for several reasons. Foremost, data are lacking to support any particular
      treatment strategy. In addition, treatment of recurrent episodes is not always
      successful, and repeated, prolonged treatment is often necessary. Identification
      of subgroups at risk for recurrent CDI may aid in diagnosing and treating these
      patients. Two likely mechanistic factors increasing the risk of recurrent CDI are
      an inadequate immune response to C. difficile toxins and persistent disruption of
      the normal colonic flora. Important epidemiologic risk factors include advanced
      age, continuation of other antibiotics, and prolonged hospital stays. Current
      guidelines recommend that the first recurrent episode be treated with the same
      agent (i.e., metronidazole or vancomycin) used for the index episode. However, if
      the first recurrence is characterized as severe, vancomycin should be used. A
      reasonable strategy for managing a subsequent episode involves tapering followed
      by pulsed doses of vancomycin. Other potentially effective strategies for
      recurrent CDI include vancomycin with adjunctive treatments, such as
      Saccharomyces boulardii, rifaximin "chaser" therapy after vancomycin,
      nitazoxanide, fecal transplantation, and intravenous immunoglobulin. New
      treatment agents that are active against C. difficile, but spare critical
      components of the normal flora, may decrease the incidence of recurrent CDI.

PMID- 19394705
TI  - Transformational leadership and depressive symptoms: a prospective study.
AB  - OBJECTIVE: The aim of this study was to examine the association between
      transformational leadership and depressive symptoms in employees working within
      healthcare. METHOD: 447 employees completed a baseline survey and 274 completed a
      follow-up survey 18 months later. 188 completed both baseline and follow-up
      survey. Transformational leadership was measured using the Global
      Transformational Leadership Scale and depression was measured using with the
      Major Depression Inventory. RESULTS: Transformational leadership was negatively
      associated with depressive symptoms at baseline (beta=-0.31, p<.01, 8% variance)
      follow-up (beta=- 0.25, p<.01, 3% variance) and prospectively (beta=- 0.21,
      p<.05, 4% variance). CONCLUSION: Managers with a transformational leadership
      style may help toward protecting employees from developing major depression.

PMID- 19394706
TI  - Expression of NK cell receptors on decidual T cells in human pregnancy.
AB  - Specific receptors enable NK cells to discriminate between cells with normal
      expression of MHC class I and cells that have low or absent expression of MHC
      class I molecules. In addition to NK cells, these receptors can be expressed on T
      cell subsets, mainly on CD8+ T cells but also on gammadeltaTCR+ T cells and CD4+
      T cells. Although the function of NK cell receptor expression on T cells is not
      completely understood, various studies have shown that they are involved in down
      regulation of T cell receptor (TCR)-mediated activation and influence effector
      functions, like cytotoxicity and cytokine production. The aim of this study was
      to analyze expression of NK cell receptors on peripheral blood and decidual T
      cells during human pregnancy using flow cytometry. We demonstrate that a
      proportion of decidual T cells express HLA-C specific killer immunoglobulin-like
      receptors (KIRs). Furthermore, a small proportion of decidual T cells express the
      HLA-E specific CD94-NKG2A inhibitory and CD94-NKG2C activating receptors.
      Decidual KIR+ and CD94-NKG2+ T cells mainly display a CD3+CD4-CD8- phenotype.
      However, decidual tissue also contains higher percentages of KIR and CD94-NKG2
      expressing CD4+ and CD8+ T cells compared to peripheral blood. So far, the
      functional capacities of decidual T cells expressing the NK cell receptors are
      unknown but NK cell receptor expression on decidual T cells may provide an
      alternative means by which decidual T cells distinguish self (maternal) cells
      from allogeneic fetal cells, and act to modulate the decidual immune response.

PMID- 19394707
TI  - Viral nanoparticles associate with regions of inflammation and blood brain
      barrier disruption during CNS infection.
AB  - Targeted treatment of inflammatory diseases of the central nervous system (CNS)
      remains problematic due to the complex pathogenesis of these disorders and
      difficulty in drug delivery. The plant virus, cowpea mosaic virus (CPMV), has
      recently been explored as a nanoparticle delivery system for therapeutics
      targeting a number of diseases including cancer and neurodegeneration. To
      understand the biodistribution of CPMV in the CNS, we examined CPMV uptake during
      infection of mice with neurotropic mouse hepatitis virus (MHV). CPMV localized
      mainly to the CNS endothelium in areas that contained an intact blood brain
      barrier. However, in inflammatory lesions containing macrophage/microglial cell
      infiltration and IgG, CPMV could be detected in the brain parenchyma.
      Furthermore, CPMV showed rapid internalization in an in vitro model of the BBB.
      These results suggest that CPMV particles could be used as a vehicle to deliver
      therapeutics to the damaged CNS during neurodegenerative and infectious diseases
      of the CNS.

PMID- 19394708
TI  - Metabolic dyslipidemia and risk of future coronary heart disease in apparently
      healthy men and women: the EPIC-Norfolk prospective population study.
AB  - BACKGROUND: The association of metabolic syndrome and risk of CHD is now well
      established. The association between 'metabolic dyslipidemia' as defined by high
      triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels
      and the risk of coronary heart disease (CHD) risk is not known. The aim of this
      study was to investigate the association between metabolic dyslipidemia, and risk
      of coronary heart disease (CHD) in apparently healthy men and women. METHODS:
      Metabolic dyslipidemia was defined by combination of increased triglyceride (TG)
      levels (>=150 mg/dl) and low high-density lipoprotein cholesterol (HDL-C) levels
      (<=50 mg/dl for women and <=40 mg/dl for men). In the EPIC-Norfolk prospective
      population study, 21,340 participants without diabetes (9326 men and 12,014
      women) were followed for a mean of 11.4 years during which 2075 CHD events
      occurred. Three multivariate models were used adjusting for other metabolic risk
      factors including low-density lipoprotein cholesterol (LDL-C). RESULTS: Compared
      to men with normal HDL and normal TG, men with metabolic dyslipidemia had an
      increased risk for CHD (HR 1.61, 95% CI 1.40-1.86). The increased risk remained
      significant after adjustment for LDL-C and other metabolic risk factors. Among
      women, metabolic dyslipidemia was associated with increased CHD risk (HR 1.78,
      95% CI 1.47-2.15). This association was lost when the model was additionally
      adjusted for other metabolic syndrome risk factors. In men and women Kaplan-Meier
      survival curves according to HDL and TG levels revealed that participants with
      metabolic dyslipidemia had poorer survival compared to people without metabolic
      dyslipidemia (logrank p<0.001 for each). CONCLUSIONS: Metabolic dyslipidemia is
      associated with an increased risk of CHD. This relationship was independent from
      LDL-C and other risk factors of the metabolic syndrome in men, but not in women.
      A better management of this phenotype via lifestyle modification or
      pharmacotherapy may be warranted.

PMID- 19394709
TI  - Accrochage and the flirting rhythms.

PMID- 19394710
TI  - Usefulness of basal B-type natriuretic peptide levels for the diagnosis of
      diastolic heart failure in young patients: an echocardiographic-catheterization
      study.
AB  - The aim of the present study was to address the diagnostic relevance of B-type
      natriuretic peptide (BNP) for the diagnosis of diastolic heart failure (DHF) in
      young patients presenting with chronic, isolated dyspnea. We prospectively
      included 26 consecutive patients with a left ventricular ejection fraction >50%
      referred for catheterism. DHF was authenticated in 15 patients with an invasive
      left ventricular end-diastolic pressure >16 mmHg. By logistic regression
      analysis, BNP was predictive of DHF (p=0.03). A cut-off value of 31 pg/ml was 67%
      sensitive and 73% specific for the diagnosis (area under the ROC curve of 0.76
      [0.55-0.9], p=0.007).

PMID- 19394711
TI  - Symptoms during ATP-test under pacing: impact on syncope recurrence and
      prediction from the ATP-test without pacing.
AB  - Syncope recurrence in patients with positive ATP-test who underwent permanent
      pacemaker implantation is suspected to be related to vagal vasodilatation. We
      studied symptoms during ATP-test in 38 temporary paced patients. Among patients
      with positive ATP-test who underwent permanent pacemaker implantation (N = 14),
      the only one patient who recurred during follow-up was symptomatic during the
      initial paced ATP-test. Symptoms during paced ATP-test were well predicted by a
      higher blood pressure (BP) drop during standard ATP-test (i.e. without pacing)
      (Area under ROC curves > 0.70 for all BP parameters except for relative diastolic
      BP drop). Moreover, BP drop during standard and paced ATP-test were significantly
      correlated (all p <= 0.03). Thus, a higher BP drop measured during ATP-test
      without pacing might help identify patients who would experience recurrences due
      to vasodilatation under permanent pacing.

PMID- 19394712
TI  - 4D-MRI analysis of lung tumor motion in patients with hemidiaphragmatic
      paralysis.
AB  - PURPOSE: To investigate the complex breathing patterns in patients with
      hemidiaphragmatic paralysis due to malignant infiltration using four-dimensional
      magnetic resonance imaging (4D-MRI). PATIENTS AND METHODS: Seven patients with
      bronchial carcinoma infiltrating the phrenic nerve were examined using 1.5 T MRI.
      The motion of the tumor and of both hemi-diaphragms were measured on dynamic 2D
      TrueFISP and 4D FLASH MRI sequences. RESULTS: For each patient, 3-6 breathing
      cycles were recorded. The respiratory-induced mean cranio-caudal displacement of
      the tumor was 6.6 mm (+/-2.8 SD). The mean displacement anterior-posterior was
      7.4 mm (+/-2.6), while right-left movement was about 7.4 mm (+/-4.5). The
      mediastinum moved sidewards during inspiration, realizing a "mediastinal shift".
      The paralyzed hemidiaphragm and the tumor showed a paradox motion during
      respiration in five patients. In two patients, the affected hemidiaphragm had a
      regular, however minimal and asynchronous motion during respiration. Respiratory
      variability of both tumor and diaphragm motions was about 20% although patients
      were instructed to breath normally. The findings showed significant differences
      compared to breathing patterns of patients without diaphragm dysfunction.
      CONCLUSION: 4D-MRI is a promising tool to analyze complex breathing patterns in
      patients with lung tumors. It should be considered for use in planning of
      radiotherapy to account for individual tumor motion.

PMID- 19394713
TI  - A wearable real-time image processor for a vision prosthesis.
AB  - Rapid progress in recent years has made implantable retinal prostheses a
      promising therapeutic option in the near future for patients with macular
      degeneration or retinitis pigmentosa. Yet little work on devices that encode
      visual images into electrical stimuli have been reported to date. This paper
      presents a wearable image processor for use as the external module of a vision
      prosthesis. It is based on a dual-core microprocessor architecture and runs the
      Linux operating system. A set of image-processing algorithms executes on the
      digital signal processor of the device, which may be controlled remotely via a
      standard desktop computer. The results indicate that a highly flexible and
      configurable image processor can be built with the dual-core architecture.
      Depending on the image-processing requirements, general-purpose embedded
      microprocessors alone may be inadequate for implementing image-processing
      strategies required by retinal prostheses.

PMID- 19394714
TI  - Discrimination of myocardial infarction stages by subjective feature extraction.
AB  - Lots of studies on myocardial infarction (MI) computer assisted diagnosis are
      based on certain important ECG components which only account for local
      information. 12-Lead ECG signals which were regarded as hyper-dimensional time
      series data were utilized to extract features from global information in this
      study. Existing feature extraction techniques for classification attempt to
      classify all the classes included. However sometimes it is more important to
      better recognize certain specific classes rather than to discriminate all the
      classes. A feature extraction method based on subjective-classification was
      proposed to discriminate the specific classes, which the classification priority
      was given subjectively, and each of the other classes was separated at the same
      time. The method includes data reduction by principal component analysis (PCA),
      data normalization by whitening transformation and derivation of projecting
      vectors for subjective-classification, etc. The data in the analysis were
      collected from PTB diagnostic ECG database. The results show that the proposed
      method can obtain a small number of effective features from 12-lead ECGs to
      better classify classes with priority, and the other classes can be classified at
      the same time.

PMID- 19394715
TI  - Health care-associated infection reporting: the need for ongoing reliability and
      validity assessment.
AB  - Government-mandated reporting of health care-associated infections (HAIs) and new
      reimbursement regulations place a premium on accurate and reliable detection of
      HAIs. This commentary addresses the challenges and opportunities of having
      consistent, well-defined, and continuous methods in place to ensure the
      reliability and validity of HAI detection and reporting. In addition, such
      procedures could support the development and expertise of infection
      preventionists. A Web-based clinical vignette model is suggested for improving
      HAI reporting for hospitals participating in the Centers for Disease Control and
      Prevention's National Healthcare Safety Network.

PMID- 19394716
TI  - [Depression in children of immigrant parents].

PMID- 19394718
TI  - [What is happening with the new diabetes mellitus drugs?].

PMID- 19394719
TI  - Discovering a new analogue of thalidomide which may be used as a potent modulator
      of TNF-alpha production.
AB  - A new series of imide derivatives related to thalidomide were synthesized and
      evaluated as modulators of TNF-alpha production. These derivatives enhance TNF
      alpha production using human leukemia HL-60 cells induced with 12-O
      tetradecanoylphorbol 13-acetate (TPA), while inhibiting TNF-alpha production
      induced with okadaic acid (OA) in the same cell line. The diphenylmaleimide
      derivative 2f, was found to be the most active product, producing a strong
      modulation of the cytokine level.

PMID- 19394717
TI  - [Interobserver agreement on electrocardiographic diagnosis of left ventricular
      hypertrophy in hypertensive patients in Andalusia. PREHVIA study].
AB  - OBJECTIVE: To assess the agreement between Primary Care (PC) doctors and a
      cardiology specialist in diagnosing left ventricular hypertrophy in the
      electrocardiograph (LVH-ECG) in hypertensive patients. DESIGN: Cross-sectional,
      multicentre study. SETTING: Andalusian Primary Care Centres. PARTICIPANTS: A
      total of 120 PC doctors who using a random sample selected patients of 35 years
      or more with AHT of at least 6 months of progression. PRIMARY VARIABLES:
      Demographic data, risk factors and cardiovascular diseases were recorded. The LVH
      ECG was evaluated by applying Cornell voltage criteria, Cornell and Sokolow-Lyon
      product. The PC researchers read the ECG first and the cardiologist made a second
      reading blind. RESULTS: A total of 570 patients (mean +/- SD of age, 65 +/- 11
      years; 54.5% females); the LVH-ECG prevalence was 13.7% (95% CI, 10.8-16.6; 12.6%
      by Cornell and 1.6% by Sokolow-Lyon). The agreement in the diagnosis between the
      PC doctors and the cardiologist was 0.378 (95% CI, 0.272-0.486; disagreements in
      15.5% of cases). The PC doctors slightly underestimated the LVH-ECG prevalence by
      Cornell and slightly overestimated it by the Sokolow-Lyon criteria. The agreement
      was also low for all of them (kappa = 0.367; 95% CI, 0.252-0.482, for Cornell,
      and kappa = 0.274; 95% CI: 0.093-0.454 for Sokolow-Lyon). CONCLUSIONS: The
      agreement between the diagnosis by the PC doctors and the cardiologist was low.
      The implications of this study suggest the need to improve the reading of ECG
      among PC doctors. The use of computerised systems could be a good option.

PMID- 19394720
TI  - [Cardiovascular manifestations of eosinophilia: clinical and echocardiographic
      presentation].
AB  - INTRODUCTION: Endomyocardial fibrosis with apical obliteration is the best known
      involvement among heart lesions induced by hypereosinophilia. However,
      hypereosinophilic heart disease may involve all three heart layers, with a
      polymorphic clinical and echocardiographic presentation. METHODS: Retrospective
      descriptive study of five patients highlighting the various manifestations of
      hypereosinophilic heart disease. RESULTS: We report five cases illustrating the
      variety of hypereosinophilic heart disease and review the pathophysiology of this
      potentially severe illness: cytotoxicity of eosinophils is mediated by the
      release of granular proteins that primarily damage the endocardium, leading to
      thrombosis and embolic complications, then to fibrosis and valvular
      complications; myocardial involvement may induce a dreadful acute eosinophilic
      myocarditis; finally, pericardial involvement may cause tamponade. CONCLUSION:
      These observations highlight the whole spectrum of the heart manifestations of
      hypereosinophilia, remind that the vital prognosis may be involved in the acute
      phase and underline that functional prognosis depends on early detection and
      treatment to reduce the risk of early thromboembolic and late fibrotic
      complications.

PMID- 19394723
TI  - [Inflammation, adipokines and obesity].
AB  - In obese subjects, there is a "low grade" inflammatory state characterized by the
      moderate but chronic systemic rise of a panel of molecules (adipokines), which
      carry out, in addition to pro- or anti-inflammatory actions, several immune or
      metabolic functions, associated with a macrophagic infiltration in adipose
      tissue. These two factors provide a better understanding of the pathophysiology
      of obesity and its potential metabolic, cardiovascular or hepatic complications.
      A small or even moderate reduction of weight significantly reduces circulating
      inflammatory markers, modulates adipose tissue profile of inflammatory genes and
      the risks associated with obesity.

PMID- 19394724
TI  - The relationship between continuing professional education and commitment to
      nursing.
AB  - Nurses have a responsibility to undertake continuing professional development to
      enable them to keep abreast with changes in health care. Acquiring new knowledge
      and skills is essential for nurses to practice safely in new and extended roles.
      Opportunities for continuing professional development are thought to increase
      retention. The aim of this study was to explore the relationship between
      undertaking continuing professional development and commitment to the profession
      and the employing National Health Service trust and to explore any differences
      between nurses in standard and extended roles. A questionnaire survey was
      undertaken with 451 nurses employed in three contrasting trusts. The
      questionnaire incorporated a validated scale to measure organisational and
      professional commitment. Three hundred and eighteen (70.5%) of the nurses had
      undertaken continuing professional development over the previous 12 months.
      Ninety nine nurses (22%) had received only mandatory training over the same
      period. There was no evidence of a relationship between professional and
      organisational commitment and undertaking continuing professional development.
      There was no evidence that specialist nurses in extended roles had undertaken the
      developmental continuing professional development that would be expected in order
      for them to acquire new competencies and skills.

PMID- 19394725
TI  - Opinions on the content and effects of clinical practice guidelines for CKD: a
      survey of nephrologists in Australia and New Zealand.
AB  - Evidence-based clinical practice guidelines have been a major development in
      nephrology internationally, but it is uncertain how the nephrology community
      regards these guidelines. This study aimed to determine the views of
      nephrologists on the content and effects of their local guidelines (Caring for
      Australasians with Renal Impairment [CARI]). In 2006, a self-administered survey
      was distributed to all Australian and New Zealand nephrologists. Seven questions
      were repeated from a similar survey in 2002. A total of 211 nephrologists (70% of
      practicing nephrologists) responded. More than 90% agreed that the CARI
      guidelines were a useful summary of evidence, and nearly 60% reported that the
      guidelines had significantly influenced their practice. The proportion of
      nephrologists reporting that the guidelines had improved patient outcomes
      increased from 14% in 2002 to 38% in 2006. The proportion of nephrologists
      indicating that the guidelines did not match the best available evidence
      decreased from 30% in 2002 to 8% in 2006. Older age and male sex showed some
      associations with a less favorable response for some domains. The CARI approach
      of rigorous evidence-based guidelines has been shown to be a successful model of
      guideline production. Almost all nephrologists regarded the CARI guidelines as
      useful evidence summaries, although only one-third believed that the guidelines
      affected health outcomes. Attitudes to the guidelines have become more favorable
      over time; this may reflect changes in the CARI process or attitudinal changes to
      evidence among nephrologists. Evaluation by the end user is fundamental to
      ensuring the applicability of guidelines in clinical practice in the future.

PMID- 19394726
TI  - Differential estimation of CKD using creatinine- versus cystatin C-based
      estimating equations by category of body mass index.
AB  - BACKGROUND: Adiposity is associated with cystatin C. Cystatin C-based glomerular
      filtration rate (GFR) equations may result in overestimation of chronic kidney
      disease (CKD) prevalence at greater body mass index (BMI) levels. STUDY DESIGN:
      Cross-sectional. SETTING & PARTICIPANTS: 6,709 US adult Third National Health and
      Nutrition Examination Survey participants. FACTOR: BMI. OUTCOME: Absolute
      percentage of difference in prevalence of stage 3 or 4 CKD between creatinine-
      and cystatin C-based estimating equations by level of BMI. MEASUREMENTS: Normal
      weight, overweight, and obesity were defined as BMI of 18.5 to less than 25.0, 25
      to less than 30.0, and 30 kg/m(2) or greater, respectively. Stage 3 or 4 CKD
      (estimated glomerular filtration rate [eGFR], 15 to 59 mL/min/1.73 m(2)) was
      defined using the 4-variable creatinine-based Modification of Diet in Renal
      Disease Study equation (eGFR(MDRD)); cystatin C level, age, sex, and race
      equation (eGFR(CysC,age,sex,race)); cystatin C-only equation (eGFR(CysC));
      cystatin C level of 1.12 mg/L or greater (increased cystatin C); and an equation
      incorporating serum creatinine level, cystatin C level, age, sex, and race
      (eGFR(Cr,CysC,age,sex,race)). RESULTS: Differences in stage 3 or 4 CKD prevalence
      estimates between eGFR(CysC,age,sex,race), eGFR(CysC), and increased cystatin C,
      separately, and eGFR(MDRD) were greater at higher BMI levels. Specifically,
      compared with estimates derived using eGFR(MDRD) for normal-weight, overweight,
      and obese participants, estimated prevalences of stage 3 or 4 CKD were 2.1%,
      3.0%, and 6.5% greater when estimated by using eGFR(CysC,age,sex,race) (P trend =
      0.005); 0.1%, 0.6%, and 2.2% greater for eGFR(CysC) (P trend = 0.03); 2.9%, 5.2%,
      and 9.5% greater for increased cystatin C (P trend < 0.001); and -0.1%, -0.4%,
      and 0.0% greater for eGFR(Cr,CysC,age,sex,race), respectively (P trend = 0.7).
      LIMITATIONS: No gold-standard measure of GFR was available. CONCLUSIONS: BMI may
      influence the estimated prevalence of stage 3 or 4 CKD when cystatin C-based
      equations are used.

PMID- 19394727
TI  - CKD and mortality risk in older people: a community-based population study in the
      United Kingdom.
AB  - BACKGROUND: The prevalence of chronic kidney disease (CKD) increases with age;
      however, the prognostic significance in older people is uncertain. This study
      aims to determine the association of CKD with all-cause and cardiovascular
      mortality in community-dwelling older people 75 years and older. STUDY DESIGN:
      Cohort study of people 75 years and older recruited in 1994 to 1999 to 1 arm of a
      trial of multidimensional health assessment with mortality follow-up. SETTING &
      PARTICIPANTS: 53 general practices in Great Britain. 15,336 (73%) of those
      eligible participated. 13,177 (86%) had serum creatinine measured at baseline.
      MAIN FACTOR: Estimated glomerular filtration rate (eGFR). OUTCOMES: All-cause and
      cardiovascular mortality. MEASUREMENTS: eGFR derived from serum creatinine level
      using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation
      in milliliters per minute per 1.73 m(2); dipstick proteinuria. Mortality by
      linkage to national death registration and death certification. RESULTS: After a
      median follow-up of 7.3 years (interquartile range, 5.0), 7,633 (58%) had died,
      42% of cardiovascular causes. In the first 2 years of follow-up, adjusted hazard
      ratios for all-cause mortality in eGFR bands of 45 to 59, 30 to 44, and less than
      30 compared with eGFR greater than 60 mL/min/1.73 m(2) were 1.13 (95% confidence
      interval, 0.93 to 1.37), 1.69 (95% confidence interval, 1.26 to 2.28), and 3.87
      (95% confidence interval, 2.78 to 5.38) in men and 1.14 (95% confidence interval,
      0.93 to 1.40), 1.33 (95% confidence interval, 1.06 to 1.68), and 2.44 (95%
      confidence interval, 1.68 to 3.56) in women, respectively. Hazard ratios were
      greater for cardiovascular mortality and lower after 2 years. Dipstick
      proteinuria was independently associated with all-cause, but not cardiovascular,
      mortality risk in both sexes. LIMITATIONS: Single serum creatinine measurement,
      no calibration of serum creatinine, MDRD Study equation not validated in older
      people. CONCLUSION: As kidney function decreases, there is a graded and
      independent increase in all-cause and cardiovascular mortality risk in older
      people 75 years and older, especially in men and those with eGFR less than 45
      mL/min/1.73 m(2). Dipstick proteinuria did not add to cardiovascular mortality
      risk in this elderly population. In older people, identification and management
      of CKD should prioritize the smaller numbers with more severe CKD.

PMID- 19394728
TI  - Effect of increasing dialyzer mass transfer area coefficient and dialysate flow
      on clearance of protein-bound solutes: a pilot crossover trial.
AB  - BACKGROUND: Protein-bound solutes are poorly cleared by means of conventional
      hemodialysis because protein binding limits the "free" solute concentration
      driving diffusion. This study tested the modeled prediction that clearances of
      bound solutes could be increased by increasing the dialyzer mass transfer area
      coefficient (K(o)A) and dialysate flow (Q(d)) to greater than the levels used in
      conventional practice. STUDY DESIGN: Pilot crossover trial. SETTING &
      PARTICIPANTS: 6 stable long-term hemodialysis patients. INTERVENTION: Study
      participants underwent an experimental dialysis treatment in which K(o)A and Q(d)
      were increased by using 2 dialyzers in series and supplying each dialyzer with a
      Q(d) of 800 mL/min by using 2 dialysis machines. Experimental clearances were
      compared with those during a conventional treatment with a single dialyzer and
      Q(d) of 800 mL/min supplied by 1 machine. OUTCOMES: Measured clearances of uremic
      solutes. MEASUREMENTS: Clearances were measured for urea nitrogen and the bound
      solutes p-cresol sulfate, indoxyl sulfate, kynurenic acid, and hippurate.
      RESULTS: Clearances for the bound solutes during conventional treatment were
      lower than for urea nitrogen (clearance values: urea nitrogen, 255 +/- 16 mL/min;
      p-cresol sulfate, 23 +/- 4 mL/min; indoxyl sulfate, 30 +/- 7 mL/min; kynurenic
      acid, 43 +/- 4 mL/min; and hippurate, 115 +/- 11 mL/min). Experimental treatment
      increased clearances of all solutes (clearance values: urea nitrogen, 318 +/- 19
      mL/min; p-cresol sulfate, 37 +/- 6 mL/min; indoxyl sulfate, 46 +/- 8 mL/min;
      kynurenic acid, 73 +/- 7 mL/min; and hippurate, 165 +/- 17 mL/min). The magnitude
      of the increases in clearance was greater for bound solutes than for urea
      nitrogen (increase in clearance: urea nitrogen, 25% +/- 6%; p-cresol sulfate, 66%
      +/- 19%; indoxyl sulfate, 57% +/- 27%; kynurenic acid, 69% +/- 5%; and hippurate,
      44% +/- 15%). LIMITATIONS: A longer term study would be required to determine
      whether increased dialytic clearance of bound solutes leads to a decrease in
      plasma solute levels. CONCLUSIONS: Dialytic clearance of protein-bound solutes
      can be increased by increasing K(o)A and Q(d) to greater than conventional
      levels.

PMID- 19394729
TI  - Polyomavirus nephropathy: a current perspective and clinical considerations.
AB  - During the last decade, the human polyomaviruses (BK virus and, much less
      commonly, JC virus) have entered the realm of routine clinical decision making
      for providers caring for kidney transplant recipients. The emergence of
      polyomavirus-associated nephropathy (PVAN) as an important clinical entity
      coincided with the development and use of more potent immunosuppression agents,
      currently the only clear risk factor for reactivation of the virus. Ongoing
      efforts to define the pathogenesis, clinical presentation, and appropriate
      management of PVAN have led to a greater ability to prevent and control viral
      induced interstitial nephritis despite continued deficiencies in our
      understanding of risk factors for disease and lack of published prospective
      polyomavirus-specific antiviral trials. The purpose of this review is to
      summarize advances made during the last decade and highlight emerging data that
      address common clinical considerations the clinician currently faces in the
      understanding and management of PVAN.

PMID- 19394730
TI  - William B. Schwartz, MD, 1923-2009.

PMID- 19394731
TI  - Sodium citrate versus heparin catheter locks for cuffed central venous catheters:
      a single-center randomized controlled trial.
AB  - BACKGROUND: Sodium citrate has antibacterial and anticoagulant properties that
      are confined to the catheter when used as a catheter lock. Studies of its use as
      a catheter lock have suggested its efficacy in preventing infection and bleeding
      complications compared with sodium heparin. STUDY DESIGN: Open-label randomized
      controlled trial of 2 catheter locks to examine the hypothesis that sodium
      citrate catheter locks will reduce catheter-related bacteremia and exit-site
      infection. SETTINGS & PARTICIPANTS: 232 consenting long-term hemodialysis
      patients in 4 satellite dialysis units to a large dialysis program with
      protocolized treatment and targets. All patients were using twin-catheter single
      lumen Tesio-Caths (MedComp, Harleysville, PA). INTERVENTION: 6 months' use of
      46.7% sodium citrate (citrate) or 5% heparin (heparin) locked postdialysis in the
      dead space of the central venous catheter. OUTCOMES & MEASUREMENTS: Primary end
      point of catheter-related bacteremia and exit-site infection. Secondary end
      points of catheter thrombosis defined by the use of urokinase lock and infusion,
      new catheter insertion, catheter-related admission, blood transfusions,
      parenteral iron, and erythropoietin requirements. RESULTS: Catheter-related
      bacteremia did not differ in the 2 groups, with an incidence of 0.7 events/1,000
      catheter-days. There was no significant difference in rates of exit-site
      infection (0.7 versus 0.5 events/1,000 catheter-days; P = 0.5). The secondary end
      point of catheter thrombosis defined by the use of a urokinase lock was
      significantly more common in the citrate group, with an incidence of 8 versus
      4.3/1,000 catheter-days (P < 0.001). Other secondary end points did not differ.
      Citrate treatment was curtailed compared with heparin because of a greater
      incidence of adverse events, with a mean treatment duration before withdrawal of
      4.8 +/- 2.0 versus 5.7 +/- 1.2 months, respectively (P < 0.001). LIMITATIONS: Low
      baseline catheter-related bacteremia and exit-site infection event rates may have
      underpowered this study. High adverse-event rates may have been related to high
      concentration citrate that led to increased overspill and reduction in lock
      volume. This may also explain the increased rates of thrombosis in this group.
      CONCLUSION: Widespread and long-term use of 46.7% citrate catheter locks with
      Tesio-Cath access is not justified by this study.

PMID- 19394732
TI  - Comorbidity and acute clinical events as determinants of C-reactive protein
      variation in hemodialysis patients: implications for patient survival.
AB  - BACKGROUND: Patients with chronic kidney disease stage 5 have high comorbidity
      and are prone to inflammation that may contribute to the high cardiovascular
      mortality risk. STUDY DESIGN: Three-month observational cohort study of prevalent
      hemodialysis patients. SETTINGS & PARTICIPANTS: 228 hemodialysis patients (44%
      women) were included, median age of 66 years, median time on dialysis therapy of
      29 months. PREDICTORS & OUTCOMES: In part 1, comorbidity and intercurrent illness
      were predictors and C-reactive protein (CRP) level was the outcome. In part 2,
      serial CRP values were predictors and survival was the outcome. MEASUREMENTS:
      High-sensitivity CRP was measured weekly and interleukin 6 (IL-6), tumor necrosis
      factor alpha, and IL-10 were measured monthly. Data for comorbidity were
      collected from patient records to calculate Davies comorbidity score, and self
      reported clinical events were recorded weekly. RESULTS: Median baseline CRP level
      was 6.7 mg/L (25th to 75th percentiles, 2.5 to 21 mg/L). Baseline CRP level
      correlated with time-averaged CRP (Spearman rho = 0.76) and individual median of
      serial CRP values (rho = 0.78; both P < 0.001). Part 1: comorbidity score was
      significantly associated with greater CRP and IL-6 levels. Age, sex, comorbidity,
      and 7 of 12 clinical events had significant effects on CRP level variation. Part
      2: during a mean follow-up of 29 months, 38% of patients died. Median and mean
      serial CRP levels were associated with a greater hazard ratio for death (1.013;
      95% confidence interval, 1.004 to 1.022) and 1.012 (95% confidence interval,
      1.004 to 1.020) than baseline, maximum, and minimum CRP values during the study.
      Other significant covariates were age, Davies risk group, dialysis vintage, and
      albumin level. LIMITATIONS: The study is based on observational data for
      prevalent dialysis patients. CONCLUSIONS: Comorbidity and clinical events are
      strongly associated with inflammation in hemodialysis patients. Despite
      variability over time, inflammation assessed by using CRP level is a strong
      predictor of mortality. Serial measurements provide additional information
      compared with a single measurement.

PMID- 19394733
TI  - Appraisal of GFR-estimating equations following kidney donation.
AB  - BACKGROUND: It is not clear which serum creatinine-based glomerular filtration
      rate (GFR)-estimating model performs best in kidney donors. STUDY DESIGN: Study
      of diagnostic accuracy. SETTING & PARTICIPANTS: From a population of 3,698 kidney
      donors, 255 donors underwent iohexol GFR measurement (mGFR). INDEX TEST
      (INTERVENTION): mGFR by means of plasma disappearance of iohexol. REFERENCE TEST
      OR OUTCOME: GFR was estimated (eGFR) by using the Cockcroft-Gault equation
      (eGFR(CG)), Mayo Clinic equation (eGFR(MC)), and Modification of Diet in Renal
      Disease (MDRD) Study equation (eGFR(MDRD)). RESULTS: Mean mGFR was 71.8 +/- 11.8
      mL/min/1.73 m(2), and 85.5% had mGFR greater than 60 mL/min/1.73 m(2). eGFR(CG)
      underestimated mGFR by 3.96 +/- 13.3 mL/min/1.73 m(2) and was within 30% of mGFR
      89.4% of the time. eGFR(MC) overestimated mGFR by 8.44 +/- 11.9 mL/min/1.73 m(2)
      and was within 30% of mGFR in 83.1% of cases. eGFR(MDRD) underestimated mGFR by
      only 0.43 +/- 11.7 mL/min/1.73 m(2), and the proportion within 30% of mGFR was
      greatest in the tested model; 94.1% of the time. However, eGFR(MC) was most
      accurate in classifying donors according to having eGFR less than 60 mL/min/1.73
      m(2). LIMITATIONS: Lack of ethnic diversity and response bias. CONCLUSIONS: The
      MDRD Study equation is least biased, and because it is routinely reported by most
      laboratories, it is the best readily available model for estimating GFR in kidney
      donors.

PMID- 19394734
TI  - Serum bicarbonate levels and the progression of kidney disease: a cohort study.
AB  - BACKGROUND: Animal models of kidney disease have linked metabolic acidosis with
      renal damage. The role of low serum bicarbonate levels in kidney disease
      progression in humans has not been studied. STUDY DESIGN: Retrospective cohort
      study. SETTING & PARTICIPANTS: Adults visiting a medical clinic in the Bronx, NY,
      from January 1, 2001, to December 31, 2003, were included in the study (n =
      5,422) and followed up until June 30, 2007. PREDICTOR: Serum bicarbonate level.
      OUTCOMES: Kidney disease progression was defined as either a decrease in
      estimated glomerular filtration rate (eGFR) by 50% or reaching an eGFR less than
      15 mL/min/1.73 m(2) (n = 337). MEASUREMENTS: Patients' baseline demographics,
      comorbid conditions, laboratory data, and socioeconomic status were recorded.
      Serial outpatient serum creatinine levels were collected (median, 5
      measurements/person). RESULTS: Mean age was 52 years, 69% were women, 45% were
      African American, 31% were Hispanic, 21% had diabetes mellitus, 41% had
      hypertension, and 9% had a baseline eGFR less than 60 mL/min/1.73 m(2). Kidney
      disease progressed as defined in 337 patients (6.2%). Compared with the reference
      group (bicarbonate level, 25 to 26 mEq/L), hazard ratios for progression after
      adjustment for potential confounders were 1.54 (95% confidence interval [CI],
      1.13 to 2.09) for bicarbonate levels of 22 mEq/L or less, 0.97 (95% CI, 0.70 to
      1.35) for 23 to 24 mEq/L, and 1.14 (95% CI, 0.84 to 1.55) for 27 mEq/L or greater
      (global P for inclusion of serum bicarbonate level in the model = 0.01). These
      results were similar using different definitions of the outcome (eGFR decrease of
      30%, 1,288 outcomes [24%]; or doubling of serum creatinine level, 268 outcomes
      [4.9%]). LIMITATIONS: Data used in the study were collected for clinical, not
      research, purposes. CONCLUSIONS: Low serum bicarbonate level is associated with
      progression of kidney disease independent of baseline eGFR and other clinical,
      demographic, and socioeconomic factors. Prospective studies are needed to confirm
      this relationship and evaluate the efficacy of alkali supplements for slowing
      progression.

PMID- 19394735
TI  - Hepatitis C seropositivity and kidney function decline among women with HIV: data
      from the Women's Interagency HIV Study.
AB  - BACKGROUND: How coinfection with hepatitis C virus (HCV) impacts on the
      trajectory of kidney function in human immunodeficiency virus (HIV)-infected
      patients is unclear. This study examined the effect of HCV infection on kidney
      function over time in women infected with HIV. STUDY DESIGN: Retrospective
      observational cohort. SETTING & PARTICIPANTS: Study sample included participants
      from the Women's Interagency HIV Study who were HIV infected and had undergone
      HCV antibody testing and serum creatinine measurement at baseline. PREDICTOR: HCV
      seropositivity. OUTCOMES & MEASUREMENT: Estimated glomerular filtration rate
      (eGFR) calculated from semi-annual serum creatinine measurements using the 4
      variable Modification of Diet in Renal Diseases (MDRD) Study equation. Linear
      mixed models were used to evaluate the independent effect of HCV seropositivity
      on eGFR over time, adjusting for demographic factors, comorbid conditions,
      illicit drug use, measures of HIV disease status, use of medications, and
      interactions with baseline low eGFR (<60 mL/min/1.73 m(2)). RESULTS: Of 2,684 HIV
      infected women, 952 (35%) were found to be HCV seropositive. In 180 women with
      chronic kidney disease (CKD) at baseline (eGFR < 60 mL/min/1.73 m(2)), HCV
      seropositivity was independently associated with a fully adjusted net decrease in
      eGFR of approximately 5% per year (95% confidence interval, 3.2 to 7.2) relative
      to women who were seronegative. In contrast, HCV infection was not independently
      associated with a decrease in eGFR in women without low eGFR at baseline (P <
      0.001 for interaction). LIMITATIONS: The MDRD Study equation has not been
      validated as a measure of GFR in persons with HIV or HCV infection. Proteinuria
      was not included in the study analysis. Because the study is observational,
      effects of residual confounding cannot be excluded. CONCLUSIONS: In HIV-infected
      women with CKD, coinfection with HCV is associated with a modest, but
      statistically significant, decrease in eGFR over time. More careful monitoring of
      kidney function may be warranted for HIV-infected patients with CKD who are also
      coinfected with HCV.

PMID- 19394736
TI  - Clinical and angiographic outcomes following percutaneous coronary intervention
      with sirolimus-eluting stents versus bare-metal stents in hemodialysis patients.
AB  - BACKGROUND: Percutaneous coronary intervention for hemodialysis patients has been
      hampered by the high rate of adverse cardiac events. Our aim was to investigate
      whether sirolimus-eluting stents (SESs) improve clinical outcomes of hemodialysis
      patients compared with bare-metal stents (BMSs). STUDY DESIGN: Retrospective
      study. SETTING & PARTICIPANTS: 123 consecutive patients on hemodialysis therapy
      treated with either an SES or BMS. There were 56 patients with 68 lesions treated
      with SESs between August 2004 and April 2006 (SES group) and 67 patients with 71
      lesions treated with BMSs 4 years before approval of SESs in Japan (BMS group).
      PREDICTOR: SES and BMS implantation for hemodialysis patients with coronary
      artery disease. OUTCOMES & MEASUREMENTS: Follow-up angiography was performed at 6
      to 8 months and clinical follow-up was obtained at 9 months after the procedure.
      Late lumen loss and major adverse cardiac events, including all-cause death,
      myocardial infarction, and target-lesion revascularization, were investigated.
      RESULTS: Clinical follow-up was obtained in all patients. Angiographic follow-up
      was obtained in 50 patients (89.3%) in the SES group and 50 patients (74.6%) in
      the BMS group. The SES group had more complex lesions than the BMS group.
      Quantitative angiographic analysis showed a significant difference for in-stent
      late lumen loss (SES, 0.62 +/- 0.75 mm; BMS, 1.07 +/- 0.75 mm; P = 0.003). Of
      angiographic restenosis lesions analyzed, a focal restenotic pattern was observed
      more frequently in the SES group than the BMS group (SES, 87.5%; BMS, 23.8%; P <
      0.001). The rate of major adverse cardiac events was significantly lower in the
      SES group (n = 14; 25.0%) than the BMS group (n = 26; 38.9%; log-rank P = 0.02).
      LIMITATIONS: Retrospective study design, small sample size, and a single-center
      study. CONCLUSIONS: Clinical and angiographic data in the present study suggest
      that SESs are more effective than BMSs in hemodialysis patients.

PMID- 19394737
TI  - The importance of residual kidney function for patients on dialysis: a critical
      review.
AB  - Increasing the dialysis dose has failed to have an impact on the mortality of
      dialysis patients. In contrast, residual kidney function (RKF) has consistently
      been a potent predictor of improved survival for both hemodialysis and peritoneal
      dialysis patients. The benefits of RKF preservation challenge historical concepts
      of dialysis adequacy that have focused principally on achieving small-solute
      clearance targets. In this review, we highlight the evidence supporting the
      impact of RKF on survival and quality of life of dialysis patients and provide a
      mechanistic framework for this relationship. Current strategies to preserve RKF
      also are reviewed, emphasizing those used in patients treated with peritoneal
      dialysis.

PMID- 19394738
TI  - Time perspective and socioeconomic status: a link to socioeconomic disparities in
      health?
AB  - Time perspective is a measure of the degree to which one's thinking is motivated
      by considerations of the future, present, or past. Time perspective has been
      proposed as a potential mediator of socioeconomic disparities in health because
      it has been associated with health behaviors and is presumed to vary with
      socioeconomic status. In this cross-sectional community-based survey of
      respondents recruited from hair salons and barber shops in a suburb of Washington
      DC, we examined the association between time perspective and both education level
      and occupation. We asked participants (N=525) to complete a questionnaire that
      included three subscales (future, present-fatalistic, and present-hedonistic) of
      the Zimbardo Time Perspective Inventory. Participants with more formal education
      and those with professional occupations had higher scores on the future time
      perspective subscale, and lower scores on the present-fatalistic subscale, than
      participants with less formal education or a non-professional occupation. Present
      fatalistic scores were also higher among participants whose parents had less
      formal education. Present-hedonistic scores were not associated with either
      education level or professional occupation. Time perspective scores were not
      independently associated with the likelihood of obesity, smoking, or exercise. In
      this community sample, future time perspective was associated with current
      socioeconomic status, and past-fatalistic time perspective was associated with
      both current and childhood socioeconomic status.

PMID- 19394739
TI  - US religious congregations and the sponsorship of health-related programs.
AB  - Despite consistent evidence that religious congregations provide health-related
      programs for their members and residents of the local community, little is known
      about the distribution of congregation-based health programs across the United
      States. Using a nationally representative sample of US congregations (n=1230) we
      employ bivariate analysis and logistic regression to identify patterns in the
      sponsorship of health-related programs by religious congregations; we then
      propose and test various explanations for these observed patterns. Our findings
      contradict the impressions given by case studies and the program evaluation
      literature and suggest: a) that congregation-based health programs may not be
      serving the neediest communities; and b) that congregations are not taking
      advantage of mechanisms intended to facilitate the provision of health-related
      services by religious congregations.

PMID- 19394740
TI  - Income incongruity, relative household income, and preterm birth in the Black
      Women's Health Study.
AB  - Relative income may be a better predictor of health outcomes than absolute
      income. We examined two measures of relative income-income incongruity and
      relative household income-in relation to preterm birth in a study of U.S. Black
      women. Income incongruity is a measure that compares the median household income
      of an individual's residential area with that of others who have the same level
      of marital status and education, but who may live in different areas. Relative
      household income is a measure that compares an individual's household income with
      the median household income of her residential area. We used data collected
      biennially (1997-2003) from participants in the Black Women's Health Study: 6257
      singleton births were included in the income incongruity analyses and 5182 in the
      relative household income analyses; 15% of the births were preterm. After
      adjusting for confounders, we found no overall association of income incongruity
      or relative household income with preterm birth. For relative household income,
      but not for income incongruity, there was suggestive evidence that neighborhood
      composition modified the association with preterm birth: higher relative
      household income was associated with higher risk of preterm birth in
      neighborhoods with a high percentage of Black residents, and higher relative
      household income was associated with lower risk in neighborhoods with a low
      percentage of Black residents.

PMID- 19394741
TI  - Why do people cooperate with medical research? Findings from three studies.
AB  - In this paper, we distinguish decisions about cooperation with medical research
      from decisions about research participation. We offer an empirical and
      theoretical exploration of why people in three different UK-based medical
      research projects chose to cooperate. Data analysis of the accounts of 128
      participants across the three studies was based on the constant comparative
      method. Participants' cooperation was engaged by a perception that they would be
      contributing to the 'public good', but they also wanted to justify their decision
      as sensible and safe. Critical to their cooperation was their belief that
      researchers would fulfil their side of the cooperative bargain, by not exposing
      participants to risks of harm or exploitation. Although participants were
      generally unaware of the details of the regulatory regime for research, they
      demonstrated a generalised reliance on regulation as a feature of everyday life
      that would provide a safe context for cooperation. In their assessment of
      particular projects, participants made judgements about whether to cooperate
      based on more specific cues, which acted as signs to assure them that researchers
      shared their cooperative intentions. These cues included organisational and
      professional credentials, the role identities and perceived trustworthiness of
      those involved in recruiting to research, and visible signs of reasonable
      practice mandated by regulatory systems. Thus participants drew on their
      understandings of an institutional field that was much broader than that of
      research alone. We propose that the social organisation of research is
      fundamental to the judgements people make about cooperation with research.
      Cooperation may be a more useful way of thinking about how people come to engage
      in collaboratively oriented actions such as research participation, rather than
      currently dominant individualistic models. Attention to the institutional context
      of research is critical to understanding what makes cooperation possible, and has
      important implications for the design of regulatory regimes for research.

PMID- 19394742
TI  - Theory driven research designs for explaining behavioural health risk
      transitions: the case of smoking.
AB  - Recent social network analyses have suggested that common chronic disease risk
      factors are more mutable than expected; raising practical considerations for
      public health interventions. Within this context, it is timely to assess the
      alternative social science reasoning being offered to explain behavioural health
      risk transitions. This paper takes up this challenge by critically reviewing the
      major theories applied to the temporal trends and sub-population variations in
      affluent country smoking behaviour. Three explanations dominate: a materialist
      approach; Bourdieu's distinctive class-based cultures; and, the spread of norms
      and emotions within social networks. We note conceptual tension when integrated
      theories are adopted. We also report on the relative absence of theoretical
      interrogation for the persistent adoption of smoking behaviours among present and
      successive lower socio-economic status (SES) cohorts. While unequal rates of
      persistence within cohorts has received some attention, the ongoing adoption of a
      non-innovative and health damaging behaviour is not well understood. To this end,
      we suggest the incorporation of several underused concepts: namely Bourdieu's
      'rules of the game' and 'symbolic violence' and 'mimesis', an aspect of social
      contagion. We conclude by describing the implications for social action of the
      alternative theories, and argue that theory driven research designs could deliver
      more efficacious evidence for interventions than the post hoc application of
      theories to existing data sets.

PMID- 19394743
TI  - [Surgical treatment of pulmonary lesions in a single lung].
AB  - We performed surgery on 4 patients who had previously undergone left
      pneumonectomy and presented a second pulmonary lesion (3 lung cancers; 1
      metastasis from colon cancer). Patients were aged between 52 and 79 years; 3 were
      men. Wedge resection was performed in 3 patients and segmentectomy in the other.
      Preoperative forced expiratory volumes in the first second were 1940 mL (72%),
      576 mL (29%), 1390 mL (63%), and 2370 mL (63%). There was no perioperative
      mortality; 1 patient presented an air leak for 7 days. Two patients were alive
      and disease-free at 12 and 15 months, and 2 died from causes unrelated to the
      tumor at 52 and 183 months. There was no deterioration in the quality of life. In
      selected cases, patients with a second tumor in a single lung can be treated
      surgically with little or no mortality and with a prolonged survival.

PMID- 19394744
TI  - [Relation between atherosclerotic calcifications detected in chest computed
      tomography and lung function].
AB  - BACKGROUND AND OBJECTIVES: A few recent epidemiological findings indicate a link
      between atherosclerosis and some lung functions. We studied further the relation
      between calcified chest atherosclerosis as seen in computed tomography (CT) and
      several lung functional parameters. PATIENTS AND METHODS: Male construction
      workers originally screened for occupational lung cancer with CT had their chest
      atherosclerosis (aorta, the origins of its cervical branches, the coronary
      arteries and heart valves) visually classified. The relation between the
      atherosclerotic calcification scores and lung function (total lung capacity
      [TLC], forced expiratory volume in one second [FEV1%], forced vital capacity
      [FVC%], maximal expiratory flow when 50% of FVC remains to be exhaled, total and
      specific diffusing capacities; all above expressed as percent of predicted value,
      and the FEV1/FVC% ratio) were studied with the general linear model adjusted for
      smoking, exposure years for asbestos, and body mass index (n=432). RESULTS: All
      lung functions except TLC showed significant negative associations with
      calcifications in aorta and in its branches. TLC showed such association only
      with atherosclerosis in the ascending aorta. CONCLUSIONS: Aortic atherosclerosis
      seems to be related with poor lung function. This may be due to deteriorated
      bronchial circulation, but other mechanisms can also be involved. Lung function
      poorer than would be expected due to pulmonary reasons may indicate aortic
      atherosclerosis.

PMID- 19394745
TI  - [Kikuchi-Fujimoto disease in an atypical site].

PMID- 19394746
TI  - [Dermatofibroma metastasizing to the lung: current treatment].
AB  - Dermatofibromas are very common skin tumors. Their typical presentation is as a
      slow-growing, firm, solitary papule. They have been described histopathologically
      as a reaction of the connective tissue of the skin or as a benign neoplasm. Cases
      of these tumors metastasizing to the lung were first reported in 1990. Since then
      12 cases with similar characteristics have been reported worldwide. We present
      the case of a young woman with a recurrent dermatofibroma on the shoulder that
      metastasized to both lungs. We discuss the histologic characteristics of this
      tumor that could raise suspicion of unusually aggressive behavior.

PMID- 19394747
TI  - [Chronic obstructive pulmonary disease in patients with acute symptomatic
      pulmonary embolism].
AB  - BACKGROUND: The diagnosis of pulmonary embolism (PE) is often complicated by the
      presence of chronic obstructive pulmonary disease (COPD). Some studies have
      suggested that patients with PE and concomitant COPD have a worse prognosis than
      patients without COPD. PATIENTS AND METHODS: Outpatients diagnosed with acute
      symptomatic PE at a university tertiary care hospital were prospectively included
      in the study. Clinical characteristics, time between onset of symptoms and
      diagnosis, and outcome were analyzed according to presence or absence of COPD.
      The primary endpoint was all-cause deaths at 3 months. RESULTS: Of 882 patients
      with a confirmed diagnosis of acute symptomatic PE, 8% (95% confidence interval
      [CI], 6%-9%) had COPD. Patients with COPD were significantly more likely to have
      a delay in diagnosis of more than 3 days and to have a low pretest probability of
      pulmonary embolism according to a standardized clinical score. The total number
      of deaths during 3 months of follow-up was 128 (14%; 95% CI, 12%-17%). Factors
      significantly associated with mortality from all causes were a history of cancer
      or immobilization, systolic blood pressure less than 100mm Hg, and arterial
      oxyhemoglobin saturation less than 90%. COPD was significantly associated with PE
      related death in the logistic regression analysis (relative risk, 2.2; 95% CI,
      1.0-5.1). CONCLUSIONS: Patients with COPD and PE more often have a lower pretest
      probability and a longer delay in diagnosis of PE. COPD is significantly
      associated with PE-related death in the 3 months following diagnosis.

PMID- 19394748
TI  - [Clinical and polysomnographic features of rapid-eye-movement-specific sleep
      disordered breathing].
AB  - OBJECTIVE: The aim of this study was to analyze the clinical and polysomnographic
      features of rapid eye movement (REM)-specific sleep disordered-breathing (SDB).
      PATIENTS AND METHODS: All cases of sleep apnea-hypopnea syndrome (SAHS) (apnea
      hypopnea index [AHI]#>10/h) diagnosed using overnight polysomnography during the
      period 2004 to 2006 were analyzed retrospectively. Those cases in which the ratio
      of AHI during REM sleep to AHI during non-REM sleep was more than 2 were
      classified as REM-specific SDB. We recorded the following data: clinical signs
      and symptoms related to SAHS, PSG results, cardiovascular risk factors, and
      previous cardiovascular events. Logistic regression analysis was used to identify
      predictors of REM-specific SDB and to analyze the possible interactions between
      variables. RESULTS: A total of 419 patients were analyzed, of whom 138 (32.9%)
      presented REM-specific SDB. This condition was more common in patients with mild
      to moderate SAHS than in those with more severe cases (odds ratio, 8.21; 95%
      confidence interval, 4.83-14.03). The variables independently associated with REM
      specific SDB in the logistic regression analysis were female sex, lower AHI, and
      higher body mass index. No interactions between the main variables studied were
      found. There were no differences between patients with REM-specific SDB and those
      with non-REM-specific SDB with regard to signs and symptoms related to SAHS,
      excessive daytime sleepiness, sleep architecture, cardiovascular risk factors, or
      history of cardiovascular episodes. CONCLUSIONS: REM-specific SDB could be
      considered an initial stage of SAHS that mainly affects obese women with mild to
      moderate sleep disorders, and that does not differ from non-REM-specific SDB in
      terms of clinical presentation, sleep architecture, or cardiovascular
      comorbidity.

PMID- 19394749
TI  - Breast cancer: from the earliest times through to the end of the 20th century.
AB  - Breast cancer is a daunting disease and constitutes a continuing medical health
      problem through the ages for millions of women worldwide. Physicians, from the
      early periods of recorded history have tried to heal breast cancer patients, with
      results that were fairly promising at times and disappointing at others. The
      science of medicine evolved through the ages under the careful scrutiny and
      critical thought of the many prominent scholars and researchers of their times
      who constantly added to the therapeutic armamentarium. Surgeons described new
      therapeutic approaches, and anatomists, through their elaborate descriptions,
      added useful insights on the art of healing. Theories about the origin of cancer
      change as new scientific data are presented and validated. Although the Middle
      Ages hindered temporarily any progress in the field of medicine, the Renaissance
      became the vaulting horse for science in its broadest sense. However, it was not
      until the 19th century, with the discovery of anesthesia, the introduction of
      antisepsis, and the establishment of microscopy that giant scientific leaps in
      the field of breast cancer treatment occurred. The 20th century with the
      development of chemotherapy and radiation and the undertaking of numerous
      clinical trials offered new insights regarding breast cancer management. This
      article attempts a historical journey through the ages unfolding the problem of
      breast cancer through the different eras.

PMID- 19394750
TI  - Inhibition of MDR1 does not sensitize primitive chronic myeloid leukemia CD34+
      cells to imatinib.
AB  - OBJECTIVE: To investigate the interaction of imatinib mesylate (IM) with the
      clinically relevant adenosine triphosphate-binding cassette efflux transporter
      MDR1 (ABCB1) in cells from patients with chronic myeloid leukemia (CML) and to
      explore whether inhibition of this transporter would improve IM's efficacy in the
      elimination of CML CD34(+) cells by increasing cell-associated drug accumulation.
      MATERIALS AND METHODS: Cells from newly diagnosed chronic-phase CML patients were
      harvested by leukapheresis and enriched to >95% CD34(+). Expression of the
      transporter gene MDR1 was performed by quantitative reverse transcription
      polymerase chain reaction. Interaction of IM with MDR1 was analyzed by substrate
      (rhodamine 123) displacement assay. Cell-associated levels of IM in CML CD34(+)
      cells were measured by high-pressure liquid chromatography. Intracellular phospho
      CrkL levels, apoptosis in total CML CD34(+) cells and high-resolution tracking of
      cell division were assayed by flow cytometry. RESULTS: Measurements of cell
      associated IM uptake showed significantly lower drug levels in CD34(+) cells,
      particularly the CD38(-) subpopulation, as compared to IM-sensitive K562 cells.
      MDR1 was expressed at low level and dye efflux studies demonstrated very little
      MDR1 activity in CML CD34(+) cells. Furthermore, combination treatment of
      primitive CML cells with IM and the MDR1 inhibitor PSC833 did not result in
      elevated cell-associated IM levels. Although we observed slightly enhanced
      cytostasis with IM when combined with PSC833, this was independent of BCR-ABL
      inhibition because no associated decrease in phospho-CrkL was observed.
      CONCLUSIONS: Our findings demonstrate that inhibition of MDR1 neither enhances
      the effect of IM against BCR-ABL activity, nor significantly potentiates IM's
      efficiency in eliminating primitive CML cells.

PMID- 19394751
TI  - Persisting NK cell alloreactivity in the presence of long-term stable
      hematopoietic chimerism.
AB  - OBJECTIVE: Like other lymphocytes, natural killer (NK) cells need to develop
      tolerance toward self. In the last decade, major progress has been made in
      understanding the molecular mechanisms behind this phenomenon. Yet the cellular
      mechanisms regulating the education of NK cells remain poorly understood. This
      study aimed to unravel the cellular mechanisms regulating NK-cell tolerance in
      the context of alloreactivity. MATERIALS AND METHODS: Using the classical hybrid
      resistance model and an in vivo cytotoxicity assay, we examined host NK-cell
      alloreactivity against donor hematopoietic cells in the presence of long-term
      stable chimerism. RESULTS: We demonstrate persisting host NK-cell alloreactivity
      against donor hematopoietic cells, despite the presence of long-term stable
      chimerism. This NK-cell alloreactivity decreases with increasing levels of
      parental chimerism. CONCLUSION: Our results indicate that long-term mixed
      hematopoietic chimerism does not necessarily imply the induction of full NK-cell
      nonresponsiveness. NK-cell nonresponsiveness is, therefore, not an absolute
      phenomenon, but represents a dynamic process, balancing NK-cell alloreactivity
      against the size of the transplanted allogeneic stem cell pool.

PMID- 19394752
TI  - Detectability of small blood vessels with high-frequency power Doppler and
      selection of wall filter cut-off velocity for microvascular imaging.
AB  - Power Doppler imaging of physiologic and pathologic angiogenesis is widely used
      in preclinical studies to track normal development, disease progression and
      treatment efficacy but can be challenging given the presence of small blood
      vessels and slow flow velocities. Power Doppler images can be plagued with false
      positive color pixels or undetected vessels, thereby complicating the
      interpretation of vascularity metrics such as color pixel density (CPD). As an
      initial step toward improved microvascular quantification, flow-phantom
      experiments were performed to establish relationships between vessel detection
      and various combinations of vessel size (160, 200, 250, 300 and 360 microm), flow
      velocity (4, 3, 2, 1 and 0.5 mm/s) and transducer frequency (30 and 40 MHz) while
      varying the wall filter cut-off velocity. Receiver operating characteristic (ROC)
      curves and areas under ROC curves indicate that good vessel detection performance
      can be achieved with a 40-MHz transducer for flow velocities > or =2 mm/s and
      with a 30-MHz transducer for flow velocities > or =1 mm/s. In the second part of
      the analysis, CPD was plotted as a function of wall filter cut-off velocity for
      each flow-phantom data set. Three distinct regions were observed: overestimation
      of CPD at low cut-offs, underestimation of CPD at high cut-offs and a plateau at
      intermediate cut-offs. The CPD at the plateau closely matched the phantom's
      vascular volume fraction and the length of the plateau corresponded with the flow
      detection performance of the Doppler system assessed using ROC analysis. Color
      pixel density vs. wall filter cut-off curves from analogous in vivo experiments
      exhibited the same shape, including a distinct CPD plateau. The similar shape of
      the flow-phantom and in vivo curves suggests that the presence of a plateau in
      vivo can be used to identify the best-estimate CPD value that can be treated as a
      quantitative vascularity metric. The ability to identify the best CPD estimate is
      expected to improve quantification of angiogenesis and anti-vascular treatment
      responses with power Doppler.

PMID- 19394753
TI  - Shockwave exerts osteogenic effect on osteoporotic bone in an ovariectomized goat
      model.
AB  - Our recent in vitro study showed that extracorporeal shock wave (ESW) stimulated
      calcium deposition in human periosteal cells. In this study, we hypothesized that
      the use of ESW could induce new bone formation in osteoporotic bone. Using our
      established osteoporotic goat model, the calcaneus, distal radius and femoral
      condyle of the left limb were treated with ESW once per month; the contralateral
      side served as the control. Bone mineral density (BMD), microarchitecture and
      dynamic histomorphometric index were evaluated after 9 months. Trabecular BMD of
      the calcaneus increased significantly by 2.90%. This finding was substantiated by
      micro-computed tomography findings showing that trabecular bone volume fraction
      and trabecular thickness of the treated calcaneus were enhanced compared with the
      contralateral control. However, significant difference could not be detected in
      the other two weight-bearing skeletal sites. Mineral apposition rates of all ESW
      treated regions were also consistently higher than those of the control. These
      findings suggest that ESW treatment could enhance local BMD by inducing new bone
      formation, yet the effect was more apparent in non-weight-bearing sites.

PMID- 19394754
TI  - High-frequency chirp ultrasound imaging with an annular array for ophthalmologic
      and small-animal imaging.
AB  - High-frequency ultrasound (HFU, >20 MHz) is an attractive means of obtaining fine
      resolution images of biological tissues for ophthalmologic, dermatological and
      small-animal imaging applications. Even with current improvements in circuit
      designs and high-frequency equipment, HFU has two inherent limitations. First,
      HFU images have a limited depth-of-field (DOF) because of the short wavelength
      and the low fixed F-number of conventional HFU transducers. Second, HFU is
      usually limited to shallow imaging because of the significant attenuation in most
      tissues. In a previous study, a five-element annular array with a 17-MHz center
      frequency was excited using chirp-coded signals, and a synthetic-focusing
      algorithm was used to extend the DOF and increase penetration depth. In the
      present study, a similar approach with two different five-element annular arrays
      operating near a center frequency of 35 MHz is implemented and validated.
      Following validation studies, the chirp-imaging methods were applied to imaging
      vitreous-hemorrhage-mimicking phantoms and mouse embryos. Images of the vitreous
      phantom showed increased sensitivity using the chirp method compared with a
      standard monocycle imaging method, and blood droplets could be visualized 4mm
      deeper into the phantom. Three-dimensional datasets of 12.5-day-old mouse embryo
      heads were acquired in utero using chirp and conventional excitations. Images
      were formed and brain ventricles were segmented and reconstructed in three
      dimensions. The brain ventricle volumes for the monocycle excitation exhibited
      artifacts that were not apparent on the chirp-based dataset reconstruction.

PMID- 19394755
TI  - Quantification of muscle volume by echography: comparison with MRI data on
      subjects in long-term bed rest.
AB  - The objective of this study was to determine the accuracy of an echographic
      method for measuring the change in leg muscle volume against the gold standard,
      magnetic resonance imaging (MRI). Leg muscle volume was measured using an
      echographic scanner, which consisted of two metallic rails on which a probe
      holder moved via an electric engine. Ten to 20 transverse muscle views were
      collected along the area scanned, and the muscle cross-sectional area (CSA, cm2)
      was measured on each of them. The integration of all the CSAs along the scanned
      area provided the muscle volume (cm3). Echographic results were compared with MRI
      data on 24 subjects undergoing 60 d of bed rest (8 control "Con," 8 with exercise
      countermeasures "Ex" and 8 with nutrition countermeasures "Nut"). The vastus
      intermedius (VI) and the vastus medialis (VM) volumes decreased significantly and
      similarly in both Con and Nut (VI, -17%; VM, -21%; p < 0.02). In the Ex group,
      the VI and VM did not change significantly. The correlation coefficient between
      the muscle volume change measured with the echographic and MRI methods was 0.78.
      The present study confirms that the echographic scanner is sufficiently accurate
      for assessing muscle volume changes and detects the effect of exercise
      countermeasures on muscle volume during long-term bed rest.

PMID- 19394756
TI  - Simulation of intracranial acoustic fields in clinical trials of
      sonothrombolysis.
AB  - Two clinical trials have used ultrasound to improve tPA thrombolysis in patients
      with acute ischemic stroke. The Combined Lysis of Thrombus in Brain Ischemia
      Using Transcranial Ultrasound and Systemic tPA (CLOTBUST) trial reported
      accelerated recanalisation of the middle cerebral artery (MCA) in patients with
      symptoms of MCA infarction, which were monitored with 2-MHz transcranial Doppler.
      In CLOTBUST, there was no increased bleeding as evidenced by cranial computed
      tomography. The Transcranial Low-Frequency Ultrasound-Mediated Thrombolysis in
      Brain Ischemia (TRUMBI) trial, which employed magnetic resonance imaging (MRI)
      before and after tPA thrombolysis, was discontinued prematurely because of an
      increased number of secondary hemorrhages, possibly related to the use of low
      frequency 300-kHz ultrasound. The purpose of our work is to help identify
      possible mechanisms of intracerebral hemorrhage resulting from sonothrombolysis
      by applying a simulation tool that estimates the pressure levels in the human
      brain that are produced with different sonothrombolysis devices. A simulation
      software based on a finite difference time domain (FDTD) three-dimensional (3D)
      scheme was developed to predict acoustic pressures in the brain. This tool
      numerically models the wave propagation through the skull and reproduces both
      ultrasound protocols of CLOTBUST and TRUMBI for analysis of the distribution of
      acoustic pressure in the brain during stroke treatment. For the simulated TRUMBI
      trial, we analyzed both a "high" and "low" hypothesis according to published
      parameters (for high and low amplitude excitations). For these hypotheses, the
      mean peak rarefactional pressures in the brain were 0.26 +/- 0.2 MPa (high
      hypothesis) and 0.06 +/- 0.05 MPa (low hypothesis), with maximal local values as
      high as 1.2 MPa (high hypothesis) and 0.27 MPa (low hypothesis) for
      configurations modelled in this study. The peak rarefactional pressure was thus
      higher than the inertial acoustic cavitation threshold in the presence of a
      standing wave in large areas of the brain, even outside the targeted clot. For
      the simulated CLOTBUST trial, the maximum peak negative pressure was less than
      0.07 MPa. This simulated pressure is below the threshold for both inertial and
      stable acoustic cavitation but likewise lower than any acoustic pressure that has
      been reported as sufficient for effective sonothrombolysis. Simulating the
      pressure field of ultrasound protocols for clinical trials of sonothrombolysis
      may help explain mechanisms of adverse effects. Such simulations could prove
      useful in the initial design and optimization of future protocols for this
      promising therapy of ischemic stroke.

PMID- 19394757
TI  - Flow volume and cross-sectional area of the extracranial vertebral arteries and
      its relation to vascular lesions or anatomical variations in the posterior
      circulation.
AB  - We examined whether the time-averaged maximum velocity (TAMV), flow volume (FV)
      or cross-sectional area (CA) in the vertebral arteries (VA) as determined by
      ultrasonography was related to vascular lesions or variations in the intracranial
      part of the posterior circulation. Three hundred nine patients without severe
      stenosis in the carotid circulation (159 males, 150 females, mean age of 69.1
      years) underwent both colour duplex ultrasonography and magnetic resonance
      angiography (MRA) and were thus analyzed. According to the MRA findings, the
      patients were divided as follows; 22 patients with severe stenosis in the
      bilateral PCA or VA or basilar artery (V group) and 287 patients without (N
      group). The N group was then further divided as follows; 144 patients with no (P0
      group); 89 with one (P1) and 54 with both posterior communicating arteries (P2)
      detected on MRA. TAMV, FV and CA were compared among these groups. Both TAMV and
      FV of V group were significantly lower than those of N group (35.3 vs. 42.6
      cm/sec in TAMV, 98.2 vs. 135.3 mL/min in FV, p < 0.001 and 0.0001, respectively).
      The FVs and CAs in the P0 through P2 groups were all significantly different
      according to the number of posterior communicating arteries (149.3 vs. 128.0 vs.
      109.8 mL/min, 22.5 vs. 20.2 vs. 16.5 mm2, both p < 0.001) while TAMVs in these
      groups did not differ substantially. The FV in both VAs were thus found to be
      related to the vascular lesions or variations in the posterior circulation.

PMID- 19394758
TI  - Serum proteomic profile of cutaneous malignant melanoma and relation to cancer
      progression: association to tumor derived alpha-N-acetylgalactosaminidase
      activity.
AB  - Currently clinical outcome in melanoma is not predictable by known serum
      biomarkers. The only reliable tool for the diagnosis of this tumor is the
      histopathological assay after surgical removing. We used a proteomic approach in
      order to identify novel non-invasive serum biomarkers of melanoma. Serum
      proteomic maps showed different patterns in relation to the presence and
      progression of the tumor in five regions of the map. Differently expressed spots
      were identified by MALDI-TOF mass spectrometry. Significant increases of
      expression were found for transthyretin (TTR) and angiotensinogen (AGT) while
      vitamin D binding protein (DBP) expression was decreased in presence of melanoma.
      Interestingly, protein expression came back to control values in stages I and II
      of the disease after 1 month since surgical removal of suspected melanoma. We
      related the decrease of DBP spot to the impaired immune response of cancer
      patients. In fact cancer cells release the alpha-N-acetylgalactosaminidase that
      can deglycosylate DBP thus interfering with the immune cascade response in which
      DBP is involved, leading to immunosuppression in melanoma patients. Specific
      enzymatic activity of serum alpha-N-acetylgalactosaminidase was significantly
      increased in stage III melanoma patients, but not in early stages. This enzymatic
      assay may provide a non-invasive way of evaluation of melanoma severity.

PMID- 19394759
TI  - Dihydroceramide intracellular increase in response to resveratrol treatment
      mediates autophagy in gastric cancer cells.
AB  - Resveratrol has both apoptosis and autophagy-promoting activities in different
      cancer cells. Dihydroceramide is the immediate precursor of the apoptotic
      mediator ceramide in the de novo sphingolipid synthesis pathway. Here we
      demonstrate that resveratrol induces autophagy in HGC-27 cells, with no sign of
      cell death. Autophagy occurs after an increase in dihydroceramides by inhibition
      of dihydroceramide desaturase. The effects of resveratrol are mimicked by a
      dihydroceramide desaturase inhibitor. These results demonstrate that resveratrol
      induced autophagy occurs with a rise in intracellular dihydroceramide levels as
      the result of inhibition of dihydroceramide desaturases activity and that
      dihydroceramide accumulation is responsible for autophagy promotion.

PMID- 19394760
TI  - Evidence for various 20q status using allelotyping, CGH arrays, and quantitative
      PCR in distal CIN colon cancers.
AB  - The genomic aberration profile of chromosome 20q in distal CIN colon carcinomas
      was analysed using allelotyping and CGH arrays. Allelotyping revealed carcinomas
      with allelic imbalance along the full long arm, and carcinomas with fully non
      aberrant 20q. Oligonucleotide-based CGH showed that among the carcinomas without
      allelic imbalance, 47% had in fact a gain. In this subgroup, quantitative PCR for
      the TOPI gene (20q12) confirmed this gain, and fluorescence in situ hybridization
      showed that the chromosome 20q gain resulted from tetra/polysomy instead of
      aneusomy. The 20q gain correlated with a high frequency of aberrations, with
      allelic imbalance at TP53 locus but not at APC locus, and carcinomas with a
      disomic 20q showed low frequency of genomic aberrations and were significantly
      associated to mucinous phenotype. The prognostic value of 20q amplification was
      not demonstrated in this study. These results indicate that on the basis of
      aberration frequency, chromosome 20q and TP53/APC locus status, distal CIN
      carcinomas harbor a high degree of genetic heterogeneity suggesting several
      pathways for carcinogenesis. This study also indicates that allelotyping needs to
      be carried out with a complementary technique, such as quantitative PCR.

PMID- 19394761
TI  - Oncogenic mutation of PIK3CA in small cell lung carcinoma: a potential
      therapeutic target pathway for chemotherapy-resistant lung cancer.
AB  - Lung cancer is one of the most prevalent cancers worldwide. This study focused on
      small cell lung cancer (SCLC), which has a poor clinical prognosis, and attempted
      to elucidate potential therapeutic molecular targets. A target-specific
      mutational search revealed mutation of the PIK3CA gene in three of 13 SCLC cell
      lines and two of 15 primary SCLCs. By introducing these mutant PIK3CA cDNAs, we
      established artificial "PIK3CA-addicted" cells and found that Tricribine, a small
      molecule inhibitor of AKT signaling that is located downstream from PIK3CA,
      significantly inhibited the growth and colony formation activity of these cells.
      Using cancer cell lines, we further showed that PIK3CA-mutated SCLC cells are
      more sensitive to Tricribine than PIK3CA wild-type cells. Additionally, we found
      that a cisplatin-resistant subclone of PIK3CA-mutant SCLC cells was equally
      sensitive to Tricribine. This study for the first time uncovered PIK3CA
      alterations in SCLC, and our findings suggest that anti-AKT molecular therapy
      could be effective for a subgroup of SCLC, which shows activation of specific
      genes, such as PIK3CA mutation, and that genetic stratification of SCLC according
      to the activation status of individual therapeutic target pathways could be
      clinically beneficial, especially for chemotherapy-resistant/relapsing tumors.

PMID- 19394762
TI  - Treatment of aqueous wastes contaminated with Congo Red dye by electrochemical
      oxidation and ozonation processes.
AB  - Synthetic aqueous wastes polluted with Congo Red (CR) have been treated by two
      advanced oxidation processes: electrochemical oxidation on boron doped diamond
      anodes (BDD-EO) and ozonation under alkaline conditions. For same concentrations,
      galvanostatic electrolyses have led to total COD and TOC removals but ozonation
      process can reach only 85% and 81% of COD and TOC removals, respectively. UV-vis
      qualitative analyses have shown different behaviors of CR molecules towards
      ozonation and electrochemical oxidation. Rapid discoloration has been observed
      during ozonation, whereas color persistence till the end of galvanostatic
      electrolyses has been seen during BDD-EO process. It seems that the oxidation
      mechanisms involved in the two processes are different: simultaneous destruction
      of azoic groups is suggested during ozonation process but consecutive destruction
      of these groups is proposed during BDD-EO. However, energetic study has evidenced
      that BDD-EO appears more efficient and more economic than ozonation in terms of
      TOC removals. These results have been explained by the fact that during BDD-EO,
      other strong oxidants electrogenerated from the electrolyte oxidation such as
      persulfates and direct-oxidation of CR and its byproducts on BDD anodes
      complement the hydroxyl radicals mediated oxidation to accomplish the total
      mineralization of organics.

PMID- 19394763
TI  - All in one: is it possible to assess all dimensions of any pain with a simple
      questionnaire?

PMID- 19394764
TI  - Personality profiles and subjective perception of pain in head pain patients.
AB  - Little or no information is available regarding the effect of the personality
      characteristics of headache sufferers on the quality of pain perception. The aim
      of this study is to investigate, in head pain sufferers, the relationship between
      the personality profile, assessed by the MMPI, and the different dimensions of
      pain (sensory, affective and evaluative), as assessed by the MPQ. Three hundred
      and seventeen patients with Migraine and/or tension-type headache (episodic or
      chronic) and myogenic facial pain were included. The Italian versions of the MMPI
      2 and MPQ were administered, and the pain level was measured by the VAS. Cluster
      analysis based on the clinical scales of MMPI identified four personality
      profiles closely corresponding to the MMPI profiles obtained by the previous
      researchers: "depressive" (Dep.), "emotionally overwhelmed" (Emot.), "conversive"
      (Conv.) and "Coper". Differences in MPQ scales between personality profiles were
      investigated by means of a general linear model (GLM), adjusting for sex, age and
      pain level and type. Results of GLM analysis showed that the affective dimension
      was significantly higher in cluster Emot. than in Dep. (p=0.027), Conv. (p=0.002)
      and Coper (p=0.003). Total PRI was significantly higher in Emot. than in Conv.
      (p=0.010). The findings of the present study suggest that a specific personality
      profile (Emot.), characterized by a heavy emotional burden, may increase the
      affective dimension of pain with respect to a depressive profile (Dep.), a
      conversive profile (Conv.) or a normal profile (Coper), independent of sex, age
      and pain level and type.

PMID- 19394766
TI  - Bee venom therapy: a probable etiology of aneurysm formation in aorta.

PMID- 19394765
TI  - Circulating endocannabinoids and N-acyl ethanolamines are differentially
      regulated in major depression and following exposure to social stress.
AB  - Central endocannabinoid signaling is known to be responsive to stressful stimuli;
      however, there is no research to date characterizing the effects of stress on
      peripheral endocannabinoid content. The current study examined serum content of
      the endocannabinoid ligands N-arachidonylethanolamide (anandamide; AEA) and 2
      arachidonoylglycerol (2-AG), and the non-cannabinoid N-acyl ethanolamine (NAE)
      molecules palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) under basal
      conditions, immediately following the Trier Social Stress Test (TSST), and 30 min
      thereafter, in 15 medication-free women diagnosed with major depression, and 15
      healthy matched controls. Basal serum concentrations of AEA and 2-AG, but not PEA
      or OEA, were significantly reduced in women with major depression relative to
      matched controls, indicating a deficit in peripheral endocannabinoid activity.
      Immediately following the TSST, serum 2-AG concentrations were increased compared
      to baseline; serum AEA concentration was unchanged at this time point. Serum
      concentrations of PEA and OEA were significantly lower than baseline 30 min
      following the cessation of the TSST. The magnitude of these responses did not
      differ between depressed and control subjects. These are the first data to
      demonstrate that the peripheral endocannabinoid/NAE system is responsive to
      exposure to stress.

PMID- 19394767
TI  - Evaluation of linear accelerator gating with real-time electromagnetic tracking.
AB  - PURPOSE: Intrafraction organ motion can produce dosimetric errors in
      radiotherapy. Commonly, the linear accelerator is gated using real-time breathing
      phase obtained by way of external sensors. However, the external anatomy does not
      always correlate well with the internal position. We examined a beam gating
      technique using signals from implanted wireless transponders that provided real
      time feedback on the tumor location without an imaging dose to the patient.
      METHODS AND MATERIALS: An interface was developed between Calypso Medical's four
      dimensional electromagnetic tracking system and a Varian Trilogy linear
      accelerator. A film phantom was mounted on a motion platform programmed with lung
      motion trajectories. Deliveries were performed when the beam was gated according
      to the signal from the wireless transponders. The dosimetric advantages of beam
      gating and the system latencies were quantified. RESULTS: Beam gating using on
      internal position monitoring provided up to a twofold increase in the dose
      gradients. The percentage of points failing to be within +/-10 cGy of the planned
      dose (maximal dose, approximately 200 cGy) was 3.4% for gating and 32.1% for no
      intervention in the presence of motion. The mean latencies between the
      transponder position and linear accelerator modulation were 75.0 +/-12.7 ms for
      beam on and 65.1 +/- 12.9 ms for beam off. CONCLUSION: We have presented the
      results from a novel method for gating the linear accelerator using trackable
      wireless internal fiducial markers without the use of ionizing radiation for
      imaging. The latencies observed were suitable for gating using electromagnetic
      fiducial markers, which results in dosimetric improvements for irradiation in the
      presence of motion.

PMID- 19394768
TI  - Isolation of Moellerella wisconsensis from the lung of a goat.
AB  - This report describes the first isolation of Moellerella wisconsensis from the
      lung of a goat in Italy and represents the fourth isolation of this rare
      enterobacterial species from non-human sources reported in the literature. In
      fact, since its first isolation, M. wisconsensis has only been described in a few
      other occasions and often in clinical samples associated with cases of human
      enteritis.

PMID- 19394769
TI  - Interactions between nutritional and opioidergic pathways in the control of LH
      secretion in male sheep.
AB  - Our aim was to determine the role of opioidergic processes in the effects of
      nutrition on the secretion of LH pulses in the mature male sheep. In the first of
      three experiments, adult Merino rams were acclimatised to a maintenance diet and
      then allocated to one of three dietary groups (n=5): continuation of the
      maintenance diet (Group M); reduction to half of the maintenance allocation
      (Group HM); or supplementation of the maintenance diet with lupin grain (Group
      HD). An initial administration of naloxone (2mg/kg body weight, i.v.) was
      followed at 40-min intervals by three further administrations (1mg/kg). Blood was
      sampled every 20 min for 12h before the initial naloxone administration and then
      for a further 6h. LH pulse frequency after naloxone treatment was significantly
      higher in Group HD than in Group HM (P<0.05). The second study tested whether the
      response to naloxone depended on calcium status. We used 22 adult Merino rams in
      two consecutive experiments, one in which the rams were fed a maintenance diet,
      and one in which the rams were fed with the maintenance diet plus 1 kg lupin
      grain for 5 weeks. In both experiments, rams were allocated to groups that
      received one of the following treatments: (a) 0.02 g/kg calcium
      borogluconate+0.2mg/kg naloxone hydrochloride (Nal+Ca(2+); n=6); (b) 0.2mg/kg
      naloxone hydrochloride (Nal; n=6); (c) 0.02 g/kg calcium borogluconate (Ca(2+);
      n=5); (d) 0.1 ml/kg NaCl 0.9% (Saline; n=5). All treatments were given as a
      single i.v. administration daily for 5 days. Blood was sampled every 20 min for
      24 h during the acclimatization period (Day 0) and on the last day (Day 5) of
      treatment. In the first study (under maintenance), none of the treatments
      affected LH pulse frequency. In the second study (the lupin-supplemented rams),
      LH pulse frequency was significantly increased (P<0.05) by the administration of
      naloxone+Ca(2+), naloxone alone and Ca(2+) alone. Overall, rams on a low plane of
      nutrition showed the smallest response to naloxone, suggesting that an
      opioidergic mechanism is not involved in the suppressive effect of restricted
      nutrition on the gonadotrophic axis. Rather, because testosterone secretion was
      increased on the high plane of nutrition, the LH responses to naloxone are better
      explained by the effects of testosterone on opioidergic mechanisms. Finally, we
      failed to observe any interaction between opioids and calcium in the control of
      LH secretion.

PMID- 19394770
TI  - Heifer nutrition during early- and mid-pregnancy alters fetal growth trajectory
      and birth weight.
AB  - Maternal nutrient intake during gestation can alter fetal growth. Whilst this has
      been studied extensively in the sheep, less is known about effects in the bovine.
      Composite-breed beef heifers were allocated to either a high (H/-=76 MJ
      metabolisable energy (ME) and 1.4 kg crude protein (CP)) or low (L/-=62 MJ ME and
      0.4 kg CP daily) nutritional treatment at artificial insemination. Half of each
      nutritional group changed to an opposite nutritional group at the end of the
      first trimester (-/H=82 MJ ME and 1.4 kg CP; -/L=62 MJ ME and 0.4 kg CP daily),
      resulting in 4 treatment groups: HH (n=16); HL (n=19); LH (n=17); LL (n=19).
      During the third trimester all heifers were fed the same diets. Fetuses were
      measured at 4-weekly intervals beginning at day 39 of gestation. Calves were also
      measured at birth for physical body variables. Low maternal nutrient intake was
      associated with decreased crown-rump length at day 39 (P<0.01) and increased
      thoracic diameter at day 95 (P<0.01). Umbilical cord diameter was reduced in L/-
      fetuses in the first trimester (P<0.05) but was greater in -/L fetuses in the
      second trimester compared to their respective H counterparts (P<0.05). Calf birth
      weight was decreased in association with -/L maternal diets (P<0.05). In
      conclusion, fetal development of cattle may be affected by maternal nutrition as
      early as day 39 of gestation. This may be followed by either compensatory fetal
      growth, or alternatively, preferential fetal tissue growth that is dependant upon
      maternal nutrition. Clearly, calf birth weight may be altered by maternal
      nutrition during mid-gestation.

PMID- 19394771
TI  - Quantitative analysis of victim demographics and injury characteristics at a
      metropolitan Medico-Legal Center.
AB  - For the timeframe of February 1st, 2003 until December 31st, 2005, all forensic
      medical experts at the Medico-Legal Center of the Institute of Legal Medicine in
      Hamburg, Germany, completed a standardized questionnaire for every consenting
      surviving violence victim (n=2733) age 14 and older. Central to the quantitative
      analysis of the data collected was the extraction of specific injury
      characteristics from the sample population. A correlation was demonstrated
      between injury typologies and four possible perpetrator-victim constellations,
      each of which was subcategorized into sexual and non-sexual assaults.

PMID- 19394772
TI  - Post-mortem magnetic resonance imaging and its irreplaceable role in determining
      CNS malformation (hydranencephaly)--case report.
AB  - Post-mortem magnetic resonance appears to be a method supplementary to classic
      pathological-anatomical autopsy in determining foetal abnormalities. Frequently,
      it plays a key role, primarily where autopsy options are in some way limited
      (developed autolysis, dilatation of the ventricular system). This case report
      demonstrates that post-mortem magnetic resonance imaging can precisely determine
      the type of congenital malformation (hydranencephaly), by contrast to ultrasound,
      with which alobar holoprosencephaly has been described, often presenting a
      differential diagnosis problem. Pathological-anatomical autopsy was significantly
      limited due to this diagnosis and this methodology was incapable of unequivocally
      determining the type of malformation. We would like to demonstrate by this case
      report the necessity of performing post-mortem magnetic resonance imaging so that
      we may precisely determine the diagnosis as requested by the parents and also be
      able to answer the question posed by risks for future pregnancies.

PMID- 19394773
TI  - [Corticosteroids in children with bacterial meningitis: indications and
      administration].
AB  - The use of dexamethasone (DXM) as adjunctive therapy for bacterial meningitis
      (BM) in infants and children has remained controversial for 20 years. In spite of
      solid pathophysiological arguments, the limited number of patients,
      methodological flaws in clinical studies taken individually and pooled into meta
      analyses, and the emergence of pneumococcal cephalosporin-resistance did not
      allow to reach a consensus on the effectiveness of DXM in the prevention of
      neurological sequelae, in the course of non Haemophilus influenzae b (Hib) BM. A
      recent meta-analysis conducted with an adequate number of patients (2,750
      patients including 2,074 infants and children below 15 years of age) demonstrated
      that DXM prevented mortality and sequelae in adults with pneumococcal meningitis
      and suggested that this efficacy could also apply to infants and children. Data
      from the active surveillance networks of pediatric BM and pneumococcal resistance
      in France suggested that DXM anti-inflammatory effect on antibiotic CSF
      penetration would not have a significant impact on the bactericidal efficacy if
      recommended dosages of cefotaxime (300 mg/kg per day) and vancomycin (60 mg/kg
      per day) were used. DXM could be considered in the early treatment of
      pneumococcal BM in infants and children in industrialized countries. But there is
      no proven efficacy of DXM in meningococcal meningitis in infants and children.

PMID- 19394774
TI  - [Epidemiology of pediatric bacterial meningitis in France].
AB  - This review of pediatric bacterial meningitis was presented in the 17th French
      Consensus Conference of antimicrobial chemotherapy. It should contribute to the
      elaboration of guidelines for the treatment of this disease. The incidence of
      bacterial meningitis rates is 44/100,000 in children under 1 year of age and
      6.9/100,000 for children between 1 and 4 years of age (in 2002). Neisseria
      meningitidis was the most frequently identified bacterium (53.7%) followed by
      Streptococcus pneumoniae (32.5%), group B streptococci (5.8%), and H. influenzae
      (3.2%). Group B streptococci predominated in children 28 days to 2 months of age
      (49.4%) and S. pneumoniae in children 2 to 12 months of age (45.2%). In children
      older than 1 year of age, N. meningitidis was the most frequently identified
      bacterium (69.7%). All N. meningitidis strains were susceptible to cefotaxim and
      ceftriaxone, one-third had decreased susceptibility to penicillin. Ten percent of
      S. pneumoniae strains were resistant to penicillin G in 2001, but this decreased
      to 3% in 2005. No strain was resistant to cefotaxim, while 6% had decreased
      susceptibility to cefotaxim in 2005 and highest MIC was 2 microg/ml. Using new
      conjugate vaccines and selective pressure on bacterial strains exhibited by
      antibiotics use have probably changed the epidemiology of pediatric bacterial
      meningitis in France.

PMID- 19394775
TI  - [Antibiotic management of pediatric presumptive bacterial meningitis (rational,
      methods, course, and follow-up)].
AB  - The epidemiology of acute community-acquired bacterial meningitis in children in
      industrialized nations was greatly modified because of recommended vaccination
      against Haemophilus influenzae b, Streptococcus pneumoniae (SP) and in some
      countries against Neisseria meningitidis (Nm) group C. However, most cases of
      bacterial meningitis are caused by SP and Nm most frequently group B, which
      validates the first intention use of cefotaxime or ceftriaxone combined or not
      with vancomycin according to the probability of pneumococcal resistance.

PMID- 19394776
TI  - Arthrography of the shoulder: a modified ultrasound guided technique of joint
      injection at the rotator interval.
AB  - OBJECTIVE: To describe an ultrasound guided technique of shoulder joint injection
      at the rotator interval space, using an endocavitary transducer and performed by
      a radiologist with no previous experience with arthrography. MATERIALS AND
      METHOD: Accuracy of the intra-articular puncture and incidence of complications
      were evaluated in 180 consecutive patients submitted to joint puncture for
      shoulder MR arthrography. RESULTS: Puncture was accomplished successfully in all
      cases, of which 92% with one attempt, and 8% with two, both well tolerated by
      patients. No relevant complications were reported after the procedure.
      CONCLUSION: This study has shown that puncture of the glenohumeral joint guided
      by ultrasound at the rotator interval space using an endocavitary transducer is
      easy and quick, even when performed by radiologists with no experience in
      arthrographic procedures.

PMID- 19394777
TI  - Ground-glass opacity: high-resolution computed tomography and 64-multi-slice
      computed tomography findings comparison.
AB  - OBJECTIVE: Comparative evaluation of ground-glass opacity using conventional high
      resolution computed tomography technique and volumetric computed tomography by 64
      row multi-slice scanner, verifying advantage of volumetric acquisition and post
      processing technique allowed by 64-row CT scanner. METHODS: Thirty-four patients,
      in which was assessed ground-glass opacity pattern by previous high-resolution
      computed tomography during a clinical-radiological follow-up for their lung
      disease, were studied by means of 64-row multi-slice computed tomography.
      Comparative evaluation of image quality was done by both CT modalities. RESULTS:
      It was reported good inter-observer agreement (k value 0.78-0.90) in detection of
      ground-glass opacity with high-resolution computed tomography technique and
      volumetric Computed Tomography acquisition with moderate increasing of intra
      observer agreement (k value 0.46) using volumetric computed tomography than high
      resolution computed tomography. CONCLUSIONS: In our experience, volumetric
      computed tomography with 64-row scanner shows good accuracy in detection of
      ground-glass opacity, providing a better spatial and temporal resolution and
      advanced post-processing technique than high-resolution computed tomography.

PMID- 19394778
TI  - Role of PROPELLER diffusion weighted imaging and apparent diffusion coefficient
      in the diagnosis of sellar and parasellar lesions.
AB  - OBJECTIVE: To evaluate the role of the apparent diffusion coefficient (ADC) using
      periodically rotated overlapping parallel lines with enhanced reconstruction
      (PROPELLER) diffusion weighted imaging (DWI) in the differentiation between
      sellar and parasellar mass lesions. MATERIALS AND METHODS: The study protocol was
      approved by our institutional review board. We retrospectively studied 60
      patients with sellar and parasellar lesions who had undergone PROPELLER DWI on a
      3-T MR imager. Conventional MRI findings were expressed as the ratio of signal
      intensity (SI) in the lesions to the normal white matter and the degree of
      contrast enhancement. ADC values were calculated as the minimum (ADC-MIN), mean
      (ADC-MEAN), and maximum (ADC-MAX). All patients underwent surgery and all
      specimens were examined histologically. Logistic discriminant analysis was
      performed by using the SI ratios on T1- and T2-weighted images (T1-WI, T2-WI),
      the degree of enhancement, and absolute ADC values as independent variables.
      RESULTS: ADC-MIN of hemorrhagic pituitary adenomas was lower than of the other
      lesions with similar appearance on conventional MRI (non-hemorrhagic pituitary
      adenomas, craniopharyngiomas, Rathke's cleft cysts; accuracy 100%); the useful
      cut-off value was 0.700 x 10(-3)mm(2)/s. ADC-MAX of meningiomas was lower than of
      non-hemorrhagic pituitary adenomas (accuracy 90.3%; p<0.01). ADC-MIN of
      craniopharyngiomas was lower than of Rathke's cleft cysts (accuracy 100%;
      p<0.05). CONCLUSION: As PROPELLER DWI is less sensitive to susceptibility
      artifacts than single-shot echoplanar DWI, it is more useful in the examination
      of sellar and parasellar lesions. Calculation of the ADC values helps to
      differentiate between various sellar and parasellar lesions.

PMID- 19394779
TI  - The superiority of 3D-CISS sequence in displaying the cisternal segment of
      facial, vestibulocochlear nerves and their abnormal changes.
AB  - OBJECTIVE: To select the best imaging method for clinical otologic patients
      through evaluating 3D constructive interference of steady state (CISS) image
      quality in visualizing the facial, vestibulocochlear nerves (CN:VII-VIII) and
      their abnormal changes. METHODS: The CN:VII-VIII as well as inner ear structures
      in 48 volunteers were examined using 3D-CISS and 3D turbo spin echo (TSE)
      sequences respectively, and displayed to the full at the reformatted and maximum
      intensity projection (MIP) images. The nerve identification and image quality
      were graded for the CN:VII-VIII as well as inner ear structures. Statistical
      analysis was performed using the Wilcoxin test, p<0.05 was considered
      significant. In addition, 8 patients with abnormality in facial or
      vestibulocochlear nerves were also examined using 3D-CISS sequence. RESULTS: The
      identification rates for the cisternal segment of facial, vestibulocochlear
      nerves and corresponding membranous labyrinth were 100%. Abnormal changes of the
      facial or vestibulocochlear nerves were clearly shown in 8 patients, among them 1
      was caused by bilateral acoustic neurinoma, 1 by cholesteatoma at
      cerebellopontine angle, 1 by arachnoid cyst, 1 by neurovascular adhesion, 4 by
      neurovascular compression. CONCLUSION: With 3D-CISS sequence the fine structure
      of the CN:VII-VIII and corresponding membranous labyrinth can be clearly
      demonstrated; lesions at the site of cerebellopontine angle can also be found
      easily.

PMID- 19394780
TI  - Diffusion tensor magnetic resonance imaging of glial brain tumors.
AB  - AIM: To evaluate the author's experience with the use of diffusion tensor
      magnetic resonance imaging (DTI) on patients with glial tumors. METHODS: A
      retrospective evaluation of a group of 24 patients with glial tumors was
      performed. There were eight patients with Grade II, eight patients with Grade III
      and eight patients with Grade IV tumors with a histologically proven diagnosis.
      All the patients underwent routine imaging including T2 weighted images,
      multidirectional diffusion weighted imaging (measured in 60 non-collinear
      directions) and T1 weighted non-enhanced and contrast enhanced images. The
      imaging sequence and evaluation software were produced by Massachusetts General
      Hospital Corporation (Boston, MA, USA). Fractional anisotropy (FA) maps were
      calculated in all patients. The white matter FA changes were assessed within the
      tumorous tissue, on the tumorous borderline and in the normally appearing white
      matter adjacent to the tumor. A three-dimensional model of the white matter tract
      was created to demonstrate the space relationship of the tumor and the capsula
      interna or corpus callosum in each case using the following fiber tracing
      parameters: FA step 0.25 and a tensor declination angle of 45 gr. An additional
      assessment of the tumorous tissue enhancement was performed. RESULTS: A uniform
      homogenous structure with sharp demargination of the Grade II tumors and the wide
      rim of the intermedial FA in all Grade III tumors respectively, were found during
      the evaluation of the FA maps. In Grade IV tumors a variable demargination was
      noted on the FA maps. The sensitivity and specificity for the discrimination of
      low- and high-grade glial tumors using FA maps was revealed to be 81% and 87%
      respectively. If the evaluation of the contrast enhancement was combined with the
      evaluation of the FA maps, both sensitivity and specificity were 100%.
      CONCLUSION: Although the evaluation of the fractional anisotropy maps is not
      sufficient for glioma grading, the combination of the contrast enhancement
      pattern and fractional anisotropy maps evaluation improves the possibility of
      distinguishing low- and high-grade glial tumors. Three-dimensional models of the
      white matter fibers in the corpus callosum and the internal capsule may be used
      in the presurgical planning.

PMID- 19394781
TI  - Whole-body MR imaging for patients with rheumatism.
AB  - WB-MRI in rheumatic diseases is still an emerging imaging tool. So far, WB-MRI in
      rheumatism is mainly used in seronegative spondyloarthropathies. In these
      diseases it has the ability to visualize the majority of involved joints and soft
      tissue structures (both active inflammatory changes and chronic structural
      abnormalities) in one examination, making it suitable for imaging of different
      forms of spondylopathies, allowing different types of joint involvement to be
      recognized and assessing both the acute symptoms of disease and the longer-term
      consequences. Its role in daily practice is not yet clear. WB-MRI is not
      recommended as a first line investigation in every patient suffering from a form
      of spondyloarthropathy, but may add important information in difficult cases.
      Moreover, WB-MRI might obtain a stronger role in the early diagnosis of
      spondyloarthritides and in the assessment of treatment response. Other rheumatic
      diseases where WB-MRI may play a role in the future are
      polymyositis/dermatomyositis, CRMO and certain forms of systemic vasculitis. WB
      MRI in rheumatism is a promising tool with great potential, however further
      systematic evaluation of its abilities and limitations in different forms of
      rheumatic diseases is awaited.

PMID- 19394782
TI  - Assessment of peritrochanteric high T2 signal depending on the age and gender of
      the patients.
AB  - INTRODUCTION: The aim of this study is to evaluate the incidence of
      peritrochanteric high T2 signal (peritrochanteric edema, peritendinitis) on
      routine MR imaging studies and to determine whether reporting peritrochanteric
      edema is always clinically relevant depending on the age and gender of the
      patients. MATERIALS AND METHODS: We evaluated 79 consecutive bilateral hip MR
      images performed in our department between January 2006 and December 2006 (57
      female, 22 male patients, mean age 49 years). Each study was evaluated for areas
      of T2 hyperintensity representing edema around the greater trochanter. Patients
      with a known fracture, tumor, history of radiation therapy, history of hip
      surgery and prothesis were excluded from the study. Patients with signal
      intensity alterations within the thickened gluteus medius/minimus tendons
      (tendinitis) or peritrochanteric bursal fluid accumulation (bursitis) were also
      excluded. All patients were scanned with our routine MR imaging protocol for hip
      imaging. RESULTS: In 55 of the 79 patients (70%) peritrochanteric edema was
      detected on MR images and 52 of these 55 patients (95%) had these changes on both
      hips. The median age was 56 years for the patients with peritrochanteric edema
      and 35.5 years for the patients without peritrochanteric edema. There was
      statistical significance between the median ages of the patients and a
      significant increased risk of peritrochanteric edema was found over 40 years of
      age. There was no significant difference between male and female patients.
      CONCLUSION: Bilateral peritrochanteric high T2 signal may be a part of the
      degeneration process and we suggest that it may not be necessarily reported if
      the clinical findings do not support greater trochanteric pain syndrome.

PMID- 19394784
TI  - Application of HILIC stationary phase to determination of dimethindene maleate in
      topical gel.
AB  - A novel high performance liquid chromatography method for the determination of
      dimethindene maleate in pharmaceutical gel using hydrophilic interaction liquid
      chromatography (HILIC) with UV detection was developed and validated. Following
      optimal conditions for the analysis of dimethindene maleate were used: analytical
      column SeQuant ZIC-HILIC (50mmx2.1mm, 5microm), and mobile phase consisted of a
      mixture of acetonitrile and aqueous solution of acetic acid (25mM) and ammonium
      acetate (2.5mM) (87.5:12.5, v:v). The analysis time was less than 3min at a flow
      rate of 0.3mlmin(-1). UV detection was performed at 258nm. The method was
      validated and system suitability parameters were evaluated. The method is
      suitable for application for routine determination of dimethindene maleate in
      topical pharmaceutical preparation.

PMID- 19394783
TI  - Assessment of left ventricular function with single breath-hold highly
      accelerated cine MRI combined with guide-point modeling.
AB  - PURPOSE: To prospectively assess the performance of highly accelerated cine MRI
      in multi-orientations combined with a new guide-point modeling post-processing
      technique (GPM approach) for assessment of left ventricular (LV) function
      compared to the standard summation of slices method based on a stack of short
      axis views (SoS approach). MATERIALS AND METHODS: 33 consecutive patients were
      examined on a 1.5T scanner with a standard steady state free precession (SSFP)
      sequence (TR, 3.0 ms; TE, 1.5m; flip angle (FA), 60 degrees ; acceleration factor
      (AF), 2) analyzed with the SoS method and a highly accelerated, single breath
      hold temporal parallel acquisition SSFP sequence (TR, 4.6 ms; TE, 1.1 ms; AF, 3)
      post-processed with the GPM method. LV function values were measured by two
      independent readers with different experience in cardiac MRI and compared by
      using the paired t-test and F-test. Inter- and intraobserver agreements were
      calculated using Bland-Altman-Plots. RESULTS: Mean acquisition and post
      processing time was significantly shorter with the GPM approach (15s/3 min versus
      360 s/6 min). For all LV function parameters interobserver agreement between the
      experienced and non-experienced reader was significantly improved when the GPM
      approach was used. However, end-diastolic and end-systolic volumes were larger
      for the GPM technique when compared to the SoS method (P<0.001), whereas ejection
      fraction estimation yielded equivalent results (P>0.121). In both readers and for
      all parameters variances did not differ significantly (P>or=0.409) and the two
      approaches showed an excellent linear correlation (r>0.951). CONCLUSION: Due to
      its accurate, fast and reproducible assessment of LV function parameters highly
      accelerated MRI combined with the GPM technique may become the technique of first
      choice for assessment of LV function in clinical routine.

PMID- 19394785
TI  - Identification of protein components and quantitative immunoassay for SEC2 in
      staphylococcin injection.
AB  - In China, staphylococcin injection has been commonly used in combined cancer
      therapy to enhance the systemic immune response and reduce the toxicities
      associated with chemotherapy or radiation therapy in the last decade. It is
      claimed that the main effective component is staphylococcal enterotoxin C2
      (SEC2). However, no standard method based on the concentration of SEC2 has been
      established for quality control of the injection products. In this study, a
      sensitive and reliable biotin-streptavidin-ELISA (BS-ELISA) method was
      established for detection and quantification of SEC2. In addition, 1-D SDS-PAGE
      coupled with nano-LC-MS/MS was performed to identify the protein components in
      the injection products from one manufacturing company. The results of the BS
      ELISA showed that SEC2 only accounted for less than 0.1% of the total protein in
      the injection products, and the nano-LC-MS/MS results showed that fifty-five
      proteins of Staphylococcus aureus were confidently identified in the injection
      solution. Seventeen out of these proteins, including SEC2, were well-known
      virulence factors. In addition, eighteen proteins of other Gram-positive bacteria
      were also confidently identified. Thus, the results indicated that SEC2 is of
      very low concentration in the injection products and the process of the injection
      preparation should be improved for health and safety consideration.

PMID- 19394786
TI  - Simultaneous quantification of 19 ginsenosides in black ginseng developed from
      Panax ginseng by HPLC-ELSD.
AB  - A high-performance liquid chromatographic method with evaporative light
      scattering detection (HPLC-ELSD) has been developed to identify and quantify 19
      ginsenosides (Rg(1), Re, Rf, Rb(1), Rc, Rb(2), Rd, F(4), Rg(6), Rk(3), Rh(4),
      20(S)-, 20(R)-Rg(3), 20(S)-, 20(R)-Rs(3), Rk(1), Rg(5), Rs(4), and Rs(5)) in
      black ginseng (BG, Korean white ginseng that was subjected to nine cycles of
      steam treatment). Ultrasonication is employed for sample preparation, and the
      analysis is achieved on a Discovery C(18) column using gradient elution of
      CH(3)CN-H(2)O-CH(3)COOH without buffer in 40min. The method was validated by
      linearity (r(2)> or =0.9994), precision (92.0-107.5%), intra- and inter-day
      accuracy (R.S.D.<3.21%), and limit of detection (LOD< or =93ng). The
      quantification method was applied to analyze the composition of ginsenosides in
      Korean white, red, and black ginsengs. During the preparatory process of BG,
      ginsenosides transform into constituents of low polarity by hydrolysis,
      isomerization, and dehydration at C-20, and hydrolysis also occurs at C-3 or C-6.
      The validated HPLC method is expected to provide the basis for the quality
      assessment of ginseng products.

PMID- 19394787
TI  - In vitro efficacy of 5 antifungal agents against Candida parapsilosis, Candida
      orthopsilosis, and Candida metapsilosis as determined by time-kill methodology.
AB  - Killing activity of amphotericin B, fluconazole, voriconazole, posaconazole, and
      5-fluorocytosine was determined against 6 Candida parapsilosis, 3 Candida
      orthopsilosis, and 4 Candida metapsilosis clinical isolates. After 24 h, 1 of 6
      C. parapsilosis, 1 of 3 C. orthopsilosis, and 3 of 4 C. metapsilosis isolates
      were killed at 1 to 4 microg/mL (1-8x MIC) amphotericin B. The remaining isolates
      were killed by 2 to 4 microg/mL amphotericin B after 48 h. Fluconazole was
      fungistatic at > or =1x MIC (0.5-2 microg/mL) against C. parapsilosis and at > or
      =2x MIC (4-8 microg/mL) against C. orthopsilosis and C. metapsilosis isolates.
      Voriconazole inhibited C. parapsilosis at > or =1x MIC (0.015-0.12 microg/mL),
      but the other 2 species were inhibited only at 4 to 8x MIC (0.25-0.5 microg/mL).
      Against C. orthopsilosis and C. metapsilosis, posaconazole was fungistatic close
      to the MIC (0.03-0.06 and 0.015-0.03 microg/mL, respectively). Against C.
      orthopsilosis and C. metapsilosis, fluconazole and voriconazole, but not
      posaconazole, seem to be less active in vitro than against C. parapsilosis.

PMID- 19394788
TI  - Impact of dissimilar susceptibility breakpoints for doripenem on susceptibility
      and carbapenem discordance for Pseudomonas aeruginosa.

PMID- 19394789
TI  - Comparative treatment and mortality correlates and adverse event profile of
      implant naltrexone and sublingual buprenorphine.
AB  - There is increasing interest in the use of implantable naltrexone as a new
      treatment for opiate dependence. This center has been one of the leaders in this
      form of treatment in Australia and has recently completed a registry-controlled
      review of our mortality data. As part of the study of the safety profile of this
      therapy, we were interested to review both the treatment correlates of previously
      presented mortality data and of adverse events. A total of 255 naltrexone implant
      therapy (NIT) and 2,518 buprenorphine (BUP) patients were followed for 1,322.22
      and 8,030.02 patient-years, respectively. NIT patients had significantly longer
      days in treatment per episode (mean +/- standard deviation, 238.32 +/- 110.11 vs.
      46.96 +/- 109.79), total treatment duration (371.21 +/- 284.64 vs. 162.50 +/-
      245.76), and mean treatment times but fewer treatment episodes than BUP (all p <
      .0001). Serious local tissue reaction or infection each occurred in 1% of 200 NIT
      episodes. These data show that NIT economizes treatment resources without
      compromising safety concerns.

PMID- 19394790
TI  - Measures of cognitive functioning as predictors of treatment outcome for cocaine
      dependence.
AB  - Amlodipine is a calcium-channel antagonist with neuropharmacological properties
      believed to be protective against cerebral hypoperfusion, microinfarcts, and
      excitoxic cell death. Based on its pharmacological properties, we hypothesized
      that amlodipine would be associated with improved attention, processing speed,
      memory, and executive functioning at treatment follow-up in 84 cocaine-dependent
      individuals enrolled in a 12-week, placebo-controlled, double-blind clinical
      trial of amlodipine. We also hypothesized that better cognitive functioning at
      baseline would be associated with reduced cocaine use (negative urine drug
      screens) and longer treatment retention (last session attended). Results
      indicated that amlodipine produced no measurable benefit in cognitive
      functioning. Percent perseverative errors on Wisconsin Card Sorting Test was
      negatively correlated with treatment retention (n = 84, r = -.350, p < .01). No
      other findings were significant. Thus, cocaine-dependent individuals who repeated
      mistakes and benefited less from corrective feedback on a problem-solving task
      discontinued treatment earlier. Notably, no other cognitive measures predicted
      treatment outcome. The observed relationship implicates the relevance of
      executive functioning to treatment outcome for cocaine dependence.

PMID- 19394791
TI  - [Glycemic control during the perioperative period].

PMID- 19394792
TI  - Health-related quality of life in end-stage COPD and lung cancer patients.
AB  - Historically, palliative care has been developed for cancer patients and is not
      yet generally available for patients suffering from chronic life-limiting
      illnesses, such as chronic obstructive pulmonary disease (COPD). To examine
      whether COPD patients experience similar or worse disease burden in comparison
      with non-small cell lung cancer (NSCLC) patients, we compared the health-related
      quality of life (HRQOL) scores of severe COPD patients with those of advanced
      NSCLC patients. We also formally updated previous evidence in this area provided
      by a landmark study published by Gore et al. in 2000. In updating this previous
      evidence, we addressed the methodological limitations of this study and a number
      of confounding variables. Eighty-two GOLD IV COPD patients and 19 Stage IIIb or
      IV NSCLC patients completed generic and disease-specific HRQOL questionnaires. We
      used an individual patient data meta-analysis to integrate the new and existing
      evidence (total n=201). Finally, to enhance between-group comparability, we
      performed a sensitivity analysis using a subgroup of patients with a similar
      degree of "terminality," namely those who had died within one year after study
      entry. Considerable differences in HRQOL were found for physical functioning,
      social functioning, mental health, general health perceptions, dyspnea,
      activities of daily living, and depression. All differences favored the NSCLC
      patients. The sensitivity analysis, using only terminal NSCLC and COPD patients,
      confirmed these findings. In conclusion, end-stage COPD patients experience poor
      HRQOL comparable to or worse than that of advanced NSCLC patients. We discuss
      these findings in the light of the notion that these COPD patients may have a
      similar need for palliative care.

PMID- 19394793
TI  - Feasibility and acceptability to patients of a longitudinal system for evaluating
      cancer-related symptoms and quality of life: pilot study of an e/Tablet data
      collection system in academic oncology.
AB  - Programmed, notebook-style, personal computers ("e/Tablets") can collect symptom
      and quality-of-life (QOL) data at the point of care. Patients use an e/Tablet in
      the clinic waiting area to complete electronic surveys. Information then travels
      wirelessly to a server, which generates a real-time report for use during the
      clinical visit. The objective of this study was to determine whether academic
      oncology patients find e/Tablets logistically acceptable and a satisfactory means
      of communicating symptoms to providers during repeated clinic visits. Sixty-six
      metastatic breast cancer patients at Duke Breast Cancer Clinic participated.
      E/Tablets were customized to electronically administer a
      satisfaction/acceptability survey, several validated questionnaires, and the
      Patient Care Monitor (PCM) review of symptoms survey. At each of the four visits
      within six months, participants completed the patient satisfaction/acceptability
      survey, which furnished data for the current analysis. Participant demographics
      were: mean age of 54 years, 77% Caucasian, and 47% with less than a college
      education. Participants reported that e/Tablets were easy to read (94%), easy to
      navigate (99%), and had a comfortable weight (90%); they found it easy to respond
      to questions using the e/Tablet (98%). Seventy-five percent initially indicated
      satisfaction with PCM for reporting symptoms; this proportion increased over
      time. By the last visit, 88% of participants indicated that they would recommend
      the PCM to other patients; 74% felt that the e/Tablet helped them remember
      symptoms to report to their clinician. E/Tablets offered a feasible and
      acceptable method for collecting longitudinal patient-reported symptom and QOL
      data within an academic, tertiary care, breast cancer clinic.

PMID- 19394794
TI  - Modeling belief systems with scale-free networks.
AB  - The evolution of belief systems has always been a focus of cognitive research. In
      this paper, we delineate a new model describing belief systems as a network of
      statements considered true. Testing the model with a small number of parameters
      enabled us to reproduce a variety of well-known mechanisms ranging from opinion
      changes to development of psychological problems. The self-organizing opinion
      structure showed a scale-free degree distribution. The novelty of our work lies
      in applying a convenient set of definitions allowing us to depict opinion network
      dynamics in a highly favorable way, which resulted in a scale-free belief
      network. As an additional benefit, we listed several conjectural consequences in
      a number of areas related to thinking and reasoning.

PMID- 19394795
TI  - The morphometric analysis of the V2 and V3 segments of the vertebral artery:
      normal values on MDCT.
AB  - A potential hazard in midline posterior fossa craniectomy may be the injury of
      vertebral artery. That's why vertebral artery evaluation prior to surgery may
      prevent dangerous complications. Advancements in multidetector computed
      tomography (MDCT) have provided detailed demonstration of the vertebral artery at
      the craniocervical junction and its relationships with atlas and axis. We aimed
      to define the normal anatomic relationship of the V2 and V3 part of the vertebral
      artery on MDCT. In total, 33 patients underwent MDCT angiography scan with
      suspected cranial aneurysm. V2 and V3 segments of vertebral artery were
      evaluated. Eight measurements (B, C, D, E, G, H, X, and Y line) were taken from
      MDCT images. For B and C, a line initially passing through the body of axis and
      spinous process and determining the midline was formed. Then, the vertical
      distance of vertebral artery from the level of transverse foramen of axis and
      loop to this midline was measured. For D and G, the vertical distance of
      vertebral artery to the midline from the upper and lower margin levels of
      transverse foramen of atlas was measured after a line establishing the midline
      passing through the anterior and posterior tubercles of atlas was drawn first.
      For E, transverse diameter of vertebral artery was measured at the loop level of
      V2 segment. For H, the vertical distance at the point where vertebral artery
      entered dura in the line passing from the midline of foramen magnum at anterior
      posterior plane was measured. For X and Y, two different points of horizontal
      part of the vertebral artery were determined. One of these two points was the
      lateral one which was the origin of the horizontal part in the transverse
      foramen, the other was the intersection point on atlas. Average distances for
      both sides from transverse foramen of the axis, the loop of axoatlantal part and
      the lower border of the atlas of the vertebral artery to the midline were 20.97
      mm on the right, 22.29 mm on the left; 27.19 mm on the right, 28.34 mm on the
      left; and 25.75 mm on the right and 27.21 mm on the left, respectively. Average
      distances for both sides from the upper border of the atlas, and at its
      penetration through dura were 27.40 mm on the right, 28.94 mm on the left; and
      10.90 mm on the right and 10.93 mm on the left, respectively. Distances between
      spinous process and intersection of vertebral artery with horizontal part were
      35.79 mm on the right and 36.63 mm on the left laterally, and 22.27 mm on the
      right and 22.62 mm on the left medially. MDCT angiography is a powerful test to
      demonstrate the vasculature of the head and neck. Bony structures and adjacent
      vessel morphology can be evaluated by this technique. The evaluation of
      craniocervical region prior to surgery with MDCT may be helpful to avoid
      intraoperative vascular injuries.

PMID- 19394796
TI  - Food intake and the occurrence of squamous cell carcinoma in different sections
      of the esophagus in Taiwanese men.
AB  - OBJECTIVE: The main objective of this study was to further elucidate the effect
      of consuming various foods on the development of squamous cell carcinoma (SCC) in
      three different sections of the esophagus. METHODS: A total of 343 patients with
      SCC of the esophagus and 755 cancer-free control subjects were recruited for this
      study from 1996 to 2005. RESULTS: We found that intake of vegetables, raw
      onions/garlic, and fruits are significantly protective against esophageal SSC
      risk, whereas intake of hot foods can significantly increase its risk. There was
      a significant inverse relation between the frequency of tea consumption and
      esophageal SCC risk (P for trend = 0.005), with a 0.5-fold lower risk associated
      with the intake of unfermented tea (green tea, oolong tea, or jasmine tea). The
      effects of dietary factors on esophageal SCC were similar in all subsites, with
      the exception of consumption of coffee. Coffee consumption was more pronounced in
      having a protective effect in the middle third section compared with the lower
      third section of the esophagus (adjusted odds ratio 0.4, 95% confidence interval
      0.2-0.9), although this protective effect was marginally significant (adjusted
      odds ratio 0.6, 95% confidence interval 0.4-1.0) against esophageal SCC in all
      subsites. Our data also suggest that discomfort when eating hot foods may exert a
      carcinogenic effect by direct contact with the esophageal mucosa and tend to have
      more harmful effects in the upper than in the lower esophagus. In contrast,
      vegetables, fruits, and tea with components that are thought to inhibit
      carcinogenesis by absorbed components affected all subsites similarly.
      CONCLUSION: Our results add additional information that certain dietary
      components may affect carcinogenesis locally and systemically.

PMID- 19394797
TI  - Single nucleotide polymorphism in esophageal cancer related gene 1: an analysis
      in resected oral squamous cell carcinoma patients.
AB  - Esophageal cancer related gene 1 (ECRG1) is a novel candidate tumor suppressor
      gene in human esophageal squamous cells. Overexpression of ECRG1 protein inhibits
      tumor cell proliferation. Genetic polymorphisms in coding sequences of the gene
      may cause functional alterations of the gene product and be associated with
      higher cancer risk and disease phenotypes. A single nucleotide polymorphism (SNP)
      (Arg290Gln) found in the coding region of ECRG1 might play a role in
      susceptibility to esophageal squamous cell carcinoma. This study examined SNPs in
      ECRG1 in a similar tumor type (oral squamous cell carcinoma; OSCC) and
      investigated the relationship between SNPs in ECRG1 and the clinical outcome of
      patients with OSCC. DNA samples of 137 OSCC patients were analyzed for SNP
      genotypes Arg/Arg, Arg/Gln and Gln/Gln in the coding region (exon 8) of ECRG1.
      SNP genotypes Arg/Arg were found in 70 (51%), Arg/Gln in 60 (43%) and Gln/Gln in
      7 (5%) patients. There was no significant association between genotypes and
      survival (p=0.77) or relapse free survival (p=0.32). The Gln/Gln genotype had the
      best survival (not significant) probably due to rare cases of SNP Gln/Gln
      genotype. Genotype Arg/Arg might be a potential negative prognostic marker in
      OSCC, but more studies with higher patient numbers are required.

PMID- 19394798
TI  - Network characteristics of idiopathic generalized epilepsies in combined MEG/EEG.
AB  - Seven patients with idiopathic generalized epilepsies were investigated using MEG
      and EEG. Spike-wave series were seen in all patients, single spikes in six. For
      both, source analysis showed most often involvement of frontal, perinsular and
      subcortical/thalamic areas. In all patients, a unilateral frontal accentuation of
      activity could be observed. Patients with juvenile myoclonic and myoclonic
      absence epilepsy presented with localizations mainly in the central and premotor
      regions versus prefrontal accentuation in the other absence patients. MEG/EEG
      source localization provides important information concerning regional network
      involvement in idiopathic generalized epilepsies. As a consequence for a
      neurophysiological concept of "generalized" epileptic seizures and syndromes, a
      third subgroup with regional activity in bilateral homologous regions can be
      differentiated next to pure focal and multifocal generalized epilepsies.

PMID- 19394799
TI  - The Val66Met polymorphism in the BDNF gene is associated with epilepsy in fragile
      X syndrome.
AB  - The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene
      may modulate the epilepsy phenotype. We investigated the impact of polymorphisms
      in the BDNF gene on clinical features in fragile X syndrome (FXS). In our study
      sample, the Met66 allele associated with epilepsy of finnish FXS men.
      Abnormalities in BDNF-mediated plasticity are shown in FXS and the present data
      suggest that the Met66 allele might predispose FXS males to epilepsy.

PMID- 19394800
TI  - Re: Serenoa repens associated with Urtica dioica (ProstaMEV) and curcumin and
      quercitin (FlogMEV) extracts are able to improve the efficacy of prulifloxacin in
      bacterial prostatitis patients: results from a prospective randomised study.

PMID- 19394801
TI  - Comparative evaluation of epidemiology and outcomes of methicillin-resistant
      Staphylococcus aureus (MRSA) USA300 infections causing community- and healthcare
      associated infections.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) USA300 clone is commonly found
      in the community and is being increasingly reported in the healthcare setting. A
      retrospective analysis was conducted to compare the epidemiology and outcomes
      between community-associated (CA) and healthcare-associated (HA) USA300 MRSA
      infections. The study enrolled 160 subjects with USA300 MRSA infections (47.5% CA
      MRSA and 52.5% HA-MRSA). Failure in the HA group was higher (38.1%) compared with
      the CA group (23.7%) (P=0.05). Predictors of failure included male gender, age,
      presence of any co-morbidity, coronary artery disease, chronic kidney disease,
      history of MRSA, previous admission, fluoroquinolone exposure, HA infection and
      osteomyelitis (P<or=0.05). Independent predictors of failure were osteomyelitis,
      history of MRSA, male gender and pneumonia. Recurrent disease was found in 32.6%
      of cases. Overall, USA300 MRSA most commonly causes infection of the skin and
      skin structure, however, 20% of subjects can experience more invasive disease
      with infection of the bloodstream, lung or bone. Failure rates are higher in
      subjects with healthcare risk factors or if the infection was acquired in the
      hospital, with these subjects experiencing more invasive infections such as
      bacteraemia, pneumonia or osteomyelitis.

PMID- 19394802
TI  - Solid-state NMR investigations of Si-29 and N-15 enriched silicon nitride.
AB  - We compare (29)Si magic-angle spinning (MAS) nuclear magnetic resonance (NMR)
      spectra from the two modifications of silicon nitride, alpha-Si(3)N(4) and beta
      Si(3)N(4), with that of a fully ((29)Si, (15)N)-enriched sample
      (29)Si(3)(15)N(4), as well as (15)N NMR spectra of Si(3)(15)N(4) (having (29)Si
      at natural abundance) and (29)Si(3)(15)N(4). We show that the (15)N NMR peak
      widths from the latter are dominated by J((29)Si-(15)N) through-bond
      interactions, leading to significantly broader NMR signals compared to those of
      Si(3)(15)N(4). By fitting calculated (29)Si NMR spectra to experimental ones, we
      obtained an estimated coupling constant J((29)Si-(15)N) of 20Hz. We provide
      (29)Si spin-lattice (T(1)) relaxation data for the (29)Si(3)(15)N(4) sample and
      chemical shift anisotropy results for the (29)Si site of beta-Si(3)N(4). Various
      factors potentially contributing to the (29)Si and (15)N NMR peak-widths of the
      various silicon nitride specimens are discussed. We also provide powder X-ray
      diffraction (XRD) and mass spectrometry data of the samples.

PMID- 19394803
TI  - Selective adsorption of plant cysteine peptidases onto TiO2.
AB  - A crude extract rich in plant cysteine peptidases was obtained from the latex of
      the fruits of Araujia hortorum, a South American climbing plant. The highly
      concentrated extract was immobilized onto titanium dioxide to produce
      biocatalysts through a simple adsorption procedure. Absorbance measurement at 280
      nm and Bradford's method for protein quantification revealed that the protein
      content of the crude extract was selectively adsorbed onto the titanium dioxide
      surface at a very high rate. In 5 min of contact with the support all protein
      present in the crude extract was selectively withdrawn from the solution, leading
      to an immobilized biocatalyst with a high protein concentration. Caseinolytic
      assays indicated that, except for the catalyst obtained with the highest crude
      amount contacted with the support, all the proteolytic activity present in the
      crude extract was adsorbed onto TiO(2). The amidasic activity of the immobilized
      catalysts (Ah/TiO(2)) was tested in the hydrolysis of a synthetic chromogenic
      substrate (PFLNA) showing partial deactivation with respect to the native enzyme.
      In amidasic activity assays the ionic strength of the buffer medium showed to be
      a key feature to consider in order to avoid protease desorption from the support,
      indicating the importance of electrostatic interactions between the enzymes and
      TiO(2). Reuse of the produced biocatalysts with PFLNA as substrate revealed that
      after five successive uses Ah/TiO(2) retained more than 20% of its initial
      activity.

PMID- 19394804
TI  - Improving radiotherapy for bladder cancer: an opportunity to integrate new
      technologies.

PMID- 19394805
TI  - Postembryonic development of the auditory system of the cicada Okanagana rimosa
      (Say) (Homoptera: Auchenorrhyncha: Cicadidae).
AB  - Cicadas (Homoptera: Auchenorrhyncha: Cicadidae) use acoustic signalling for mate
      attraction and perceive auditory signals by a tympanal organ in the second
      abdominal segment. The main structural features of the ear are the tympanum, the
      sensory organ consisting of numerous scolopidial cells, and the cuticular link
      between sensory neurones and tympanum (tympanal ridge and apodeme). Here, a first
      investigation of the postembryonic development of the auditory system is
      presented. In insects, sensory neurones usually differentiate during
      embryogenesis, and sound-perceiving structures form during postembryogenesis.
      Cicadas have an elongated and subterranian postembryogenesis which can take
      several years until the final moult. The neuroanatomy and functional morphology
      of the auditory system of the cicada Okanagana rimosa (Say) are documented for
      the adult and the three last larval stages. The sensory organ and the projection
      of sensory afferents to the CNS are present in the earliest stages investigated.
      The cuticular structures of the tympanum, the tympanal frame holding the
      tympanum, and the tympanal ridge differentiate in the later stages of
      postembryogenesis. Thus, despite the different life styles of larvae and adults,
      the neuronal components of the cicada auditory system develop already during
      embryogenesis or early postembryogenesis, and sound-perceiving structures like
      tympana are elaborated later in postembryogenesis. The life cycle allows
      comparison of cicada development to other hemimetabolous insects with respect to
      the influence of specially adapted life cycle stages on auditory maturation. The
      neuronal development of the auditory system conforms to the timing in other
      hemimetabolous insects.

PMID- 19394806
TI  - Total flavonoids of Herba Epimedii improves osteogenesis and inhibits
      osteoclastogenesis of human mesenchymal stem cells.
AB  - INTRODUCTION: In China Herba Epimedii is one of the most common herbs that could
      be prescribed for treating osteoporosis. It is known to increase the overall
      mineral content, therefore, to promote bone formation and to increase lumbar bone
      mineral density (BMD). The present study was aimed at investigating the effect of
      flavonoids of Herba Epimedii (HEF) on osteogenesis in human MSCs. METHODS: The
      human bone marrow-derived MSCs (BM-MSCs) were isolated and their osteogenic
      differentiation was evaluated by their alkaline phosphatase (ALP) activities and
      level of mineralization. After treating with total flavonoids during osteogenic
      differentiation process, differential mRNA expression was examined by RT-PCR.
      RESULTS: The total time needed for osteogenic differentiation of BM-MSCs was
      significantly shortened by adding HEF. Up-regulation of mRNA expression by HEF
      was observed for several marker genes and osteogenic regulators. HEF was also
      found to inhibit osteoclastogenesis of MSCs by enhancing the ratio OPG/RANKL.
      CONCLUSIONS: Our study demonstrated that the HEF could improve osteogenic
      differentiation and inhibit the osteoclast differentiation of BM-MSCs
      concurrently.

PMID- 19394807
TI  - Paper submission and acceptance criteria.

PMID- 19394808
TI  - Factors affecting degradation of polyethylene terephthalate (PET) during pre
      flotation conditioning.
AB  - In general, plastics are exposed to different degrading agents in every procedure
      involved in their recovery from waste mixture and from subsequent recycling. In
      this study, two methods of pre-flotation conditioning were used to determine how
      these methods affect the general properties of the pre-conditioned PET particles
      to be recovered from the PET-PVC mixture. The first method comprised the
      conditioning of PET samples using an alkaline solution of nonionic surfactant
      (Triton X-100) based on the patent by the Goodyear Tire and Rubber Company. The
      second method, developed in this study, was a conditioning process which used an
      alkali-less solution of the same nonionic surfactant (Triton X-100) used in the
      first method. The following analytical methods were used to characterize
      properties of the pre-conditioned PET samples that were correlated to relative
      degradation of the samples: differential scanning calorimetry (DSC), for thermal
      behavior of the samples; FT-IR spectroscopy, for functional groups present in the
      samples; and, Pohl's method, for carboxyl end-group concentration count. Results
      show that in addition to water the presence of NaOH in the conditioning solution
      contributes to the further degradation of the polymer.

PMID- 19394809
TI  - Superparamagnetic microsphere-assisted fluoroimmunoassay for rapid assessment of
      acute myocardial infarction.
AB  - Rapid assessment of acute myocardial infarction (AMI) was successfully
      demonstrated using an improved superparamagnetic polymer microsphere-assisted
      sandwich fluoroimmunoassay to detect two early cardiac markers-myoglobin and
      human heart-type fatty acid binding protein (H-FABP). This assay used a
      preparation of superparamagnetic poly(styrene-divinylbenzene-acrylamide)
      microspheres, glutaraldehyde-coupled capture antibodies (monoclonal anti
      myoglobin 7C3 and anti-H-FABP 10E1) grafted onto the polymer microspheres, and a
      sequential sandwich fluoroimmunoassay using detection antibodies (FITC-labeled
      anti-myoglobin 4E2 and FITC-labeled anti-H-FABP 9F3). Characterization of the
      polymer microspheres by TEM, SEM and Fourier transform infrared spectroscopy (FT
      IR) showed that the microspheres were uniformly round with an average diameter of
      1.12 microm, and had a Fe(3)O(4)-polymer core-shell structure (shell thickness
      was about 84 nm) with 0.22 mmol/g amino groups on their surfaces. The magnetic
      behavior of the Fe(3)O(4)-polymer microspheres was superparamagnetic (M(s)=13
      emu/g, H(c)=13.1 Oe). Fluorescence images of the post-immunoassay microspheres
      recorded using a confocal laser-scanning microscope showed that the average
      fluorescence intensity was correlated with the concentration of cardiac markers,
      in agreement with the results obtained by an F-4500 FL spectrophotometer; this
      indicated that the fluoroimmunoassay could be used to semi-quantitatively detect
      both myoglobin and H-FABP. The detection limit was 25 ng/mL for myoglobin and 1
      ng/mL for H-FABP.

PMID- 19394810
TI  - Molecularly imprinted nanopatterns for the recognition of biological warfare
      agent ricin.
AB  - Molecularly imprinted polymer (MIP) for biological warfare agent (BWA) ricin was
      synthesized using silanes in order to avoid harsh environments during the
      synthesis of MIP. The synthesized MIP was utilized for the recognition of ricin.
      The complete removal of ricin from polymer was confirmed by fluorescence
      spectrometer and SEM-EDAX. SEM and EDAX studies confirmed the attachment of
      silane polymer on the surface of silica gel matrix. SEM image of Ricin-MIP
      exhibited nanopatterns and it was found to be entirely different from the SEM
      image of non-imprinted polymer (NIP). BET surface area analysis revealed more
      surface area (227 m(2)/g) for Ricin-MIP than that of NIP (143 m(2)/g). In
      addition, surface area study also showed more pore volume (0.5010 cm(3)/g) for
      Ricin-MIP than that of NIP (0.2828 cm(3)/g) at 12 nm pore diameter confirming the
      presence of imprinted sites for ricin as the reported diameter of ricin is 12 nm.
      The recognition and rebinding ability of the Ricin-MIP was tested in aqueous
      solution. Ricin-MIP rebound more ricin when compared to the NIP. Chromatogram
      obtained with Ricin-MIP exhibited two peaks due to imprinting, however,
      chromatogram of NIP exhibited only one peak for free ricin. SDS-PAGE result
      confirmed the second peak observed in chromatogram of Ricin-MIP as ricin peak.
      Ricin-MIP exhibited an imprinting efficiency of 1.76 and it also showed 10%
      interference from the structurally similar protein abrin.

PMID- 19394811
TI  - Integrated studies of biology: multiplexed imaging assays from molecules to man
      and back.

PMID- 19394812
TI  - Nothing about protein structure classification makes sense except in the light of
      evolution.
AB  - In this, the 200th anniversary of Charles Darwin's birth and the 150th
      anniversary of the publication of the Origin of Species, it is fitting to revisit
      the classification of protein structures from an evolutionary perspective.
      Existing classifications use homologous sequence relationships, but knowing that
      structure is much more conserved that sequence creates an iterative loop from
      which structures can be further classified beyond that of the domain, thereby
      teasing out distant evolutionary relationships. The desired classification scheme
      is then one in which a fold is merely semantics and structure can be classified
      as either ancestral or derived.

PMID- 19394813
TI  - Germline variations of the MALT1 gene as risk factors in the development of
      primary gastric B-cell lymphoma.
AB  - Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a histologically
      distinct tumour derived from MALT acquired as a result of Helicobacter pylori
      infection. The genetic susceptibility to develop primary gastric B-cell lymphoma
      in patients with chronic H. pylori infection is unknown. MALT1 plays a key role
      in malignant B-cell transformation and lymphoma progression. Thus, we
      investigated germline variations of MALT1 as risk factors for gastric lymphoma in
      a large cohort from a European multicentre study and in total 214 lymphoma
      patients, 593 H. pylori infected controls and 348 healthy blood donors were
      genotyped for four single nucleotide polymorphisms (SNPs) covering the MALT1
      locus by Taqman technology. Haplotype and single marker analyses were conducted
      for association testing in a case-control setting. A distinct haplotype was
      identified that showed a trend towards protection from high-grade and low-grade
      lymphomas. In single marker analysis individuals homozygous for the rare allele G
      of SNP3 (rs12969413) were significantly protected only from gastric high-grade
      lymphoma compared with controls (p=0.002, odds ratio (OR): 0.2, Wald 95%
      confidence interval (CI): 0.1<OR<0.6). This association could not be confirmed in
      a second independent cohort of high-grade lymphoma patients from the Lymph node
      registry in Kiel (p=0.531, OR: 0.8, Wald 95% CI: 0.4<OR<1.5). Due to the fact
      that SNPs 2, 3 and 4 are arranged in one LD block exhibiting nearly complete
      linkage disequilibrium it is rather unlikely that germline variations of MALT1
      might be involved in the pathogenesis of gastric lymphoma. This is the first
      genetic association study that investigated polymorphisms of MALT1 as genetic
      risk factors in the development of primary gastric lymphoma.

PMID- 19394814
TI  - Clinical significance and treatment of biochemical recurrence after definitive
      therapy for localized prostate cancer.
AB  - PURPOSE: Radical prostatectomy and external beam radiation therapy are the
      established and definitive interventions for clinically localized prostate
      cancer. These treatment modalities are yet subject to failure observed first by
      biochemical recurrence, defined by increases in the serum PSA level. We
      investigated the significance of biochemical recurrence after definitive therapy
      and the available salvage therapy options for cancer recurrence. METHODS: A
      literature search was performed in PubMed, and applicable studies addressing
      biochemical recurrence and salvage options after radical prostatectomy or
      external beam radiation therapy were reviewed. RESULTS: After radical
      prostatectomy, a detectable serum PSA level indicates biochemical recurrence.
      Whether to administer salvage therapy locally or systemically depends largely on
      prognostic factors including PSA doubling time, Gleason's score, pathologic
      stage, and the time interval between radical prostatectomy and biochemical
      recurrence. Early initiation of salvage therapy has been shown to significantly
      impact on cancer outcomes. After external beam radiation therapy, no single PSA
      level can define biochemical recurrence. Instead, it has been defined by
      increases in the PSA level above the nadir. Following radiation therapy, PSA
      doubling time and Gleason score play important roles in determining the need for
      local versus systemic salvage therapy. CONCLUSIONS: After the diagnosis of
      biochemical recurrence, it is critical to perform a timely clinical assessment
      using the prognostic factors mentioned above. Prompt initiation of salvage
      therapy may prevent subsequent clinical progression and prostate cancer-specific
      mortality.

PMID- 19394815
TI  - Drugs of anaesthesia and cancer.
AB  - Anaesthesia represents one of the most important medical advances in history,
      and, nowadays, can widely be considered safe, thanks to the discovery of new
      drugs and the adoption of modern technologies. Nevertheless, anaesthetic
      practices still represent cause for concern regarding the consequences they
      produce. Various anaesthetics are frequently used without knowing their effects
      on specific diseases: despite having been reported that invasion or metastasis of
      cancer cells easily occurs during surgical procedures, numerous anaesthetics are
      used for cancer resection even if their effect on the behaviour of cancer cells
      is unclear. Guidelines for a proper use of anaesthetics in cancer surgery are not
      available, therefore, the aim of the present review is to survey available up-to
      date information on the effects of the most used drugs in anaesthesia (volatile
      and intravenous anaesthetics, nitrous oxide, opioids, local anaesthetics and
      neuromuscular blocking drugs) in correlation to cancer. This kind of knowledge
      could be a basic valuable support to improve anaesthesia performance and patient
      safety.

PMID- 19394816
TI  - An overview of coagulation disorders in cancer patients.
AB  - A diversity of coagulation disorders in cancer patients arise from tumor-specific
      growth characteristics, neoangiogenesis with impaired endothelial lining,
      defective myelopoiesis, hypoproteinemia or metastatic lesions growth with organ
      dysfunction. Recent investigations have found a clinically relevant correlation
      of coagulation disorders and tumor growth. These prompted new therapeutic
      strategies focused on growth factors with the aim to control tumor metastasis,
      particularly if used for the treatment of micrometastatic disease. However, such
      treatment may lead to the life threatening coagulation imbalance. A coagulation
      homeostasis may become further impaired after nonsurgical cancer therapy,
      especially after preoperative irradiation, which produces lesions precipitating
      both bleeding and thrombosis. Anticancer chemotherapy may affect liver function
      and decrease the synthesis of both procoagulation and anticoagulation factors.
      The most of chemotherapeutic protocols affect platelet synthesis, which arises as
      a principal dose-limiting side effect. It was observed both during combined
      systemic chemotherapy and local antitumor therapy. Although the side effects
      produced by chemotherapy are reversible, endothelial lesions may persist for many
      years after the anticancer treatment. Instead of cancer patients, there's a
      growing cohort of patients with nonmalignant diseases who use cytostatics in the
      perioperative period, and are candidates for surgical procedures not related to
      their malignant disease, i.e. hernia repair. In this patient population a special
      attention must be paid to the preoperative evaluation of coagulation status and
      thromboprophylaxis. This overview reminds the most common coagulation disorders
      in cancer patients in the perioperative period. It emphasizes the need for proper
      patient monitoring which may facilitate the diagnostics and treatment of cancer
      related coagulation disorders in the perioperative setting.

PMID- 19394817
TI  - Prospects for phosphorus recovery from poultry litter.
AB  - Land disposal of poultry litter is an environmental concern often associated to
      excess phosphorus (P) in soils and potential water pollution in regions with
      intense poultry production. Although poultry litter can be moved off the farm and
      traded as fertilizer, its transportation becomes less economical with increasing
      distances from the farm. Thus, new litter management alternatives are needed to
      reduce the environmental impact of P litter application to land. This paper
      summarizes established and emerging alternative technologies in the U.S. that
      facilitate handling, concentration, and transporting of litter P. Furthermore, it
      examines the potential integration of technologies into poultry litter management
      systems that could reduce poultry litter volume and increase P content in litter
      byproducts. The adoption of alternative technologies may encourage new
      opportunities to produce bio-energy, fertilizer, and other valuable P byproducts
      from poultry litter while reducing environmental impact and promoting sustainable
      poultry production.

PMID- 19394818
TI  - Fermentative hydrogen production from tofu-processing waste and anaerobic
      digester sludge using microbial consortium.
AB  - The combination of tofu-processing waste and anaerobic digester sludge was
      studied for its fermentative H(2) production capacity in batch and continuous
      modes using a thermophilic mixed culture. Heat-treatment (110 degrees C, 30 min)
      in the presence of 0.5% HCl increased the soluble carbohydrate content of the
      tofu waste from 2.2 to 10.4 g/l. Anaerobic digester sludge was added to the tofu
      waste for supplementary nutrients with the optimal mixing ratio of 20% (v/v)
      under batch conditions. In continuous experiments, the effects of HRT(hydraulic
      retention time) and pH were investigated for the ranges of 2-6h and 5.0-6.0,
      respectively. The maximal H(2) production rate (12.0 l H(2)/l/day) and yield (2.3
      mol H(2)/mol glucose equivalent) were obtained at HRT 4h and pH 5.5 while
      maintaining the head space gas at 50-60% (v/v) of H(2) without CH(4). This study
      indicates that the combination of tofu-processing waste and digester sludge can
      be considered to be one of the most promising forms of organic waste for
      continuous H(2) production.

PMID- 19394819
TI  - Removal of hydrogen sulfide using crushed oyster shell from pore water to
      remediate organically enriched coastal marine sediments.
AB  - Hydrogen sulfide is highly toxic and fatal to benthic organisms as well as
      causing depletion of dissolved oxygen and generating blue tide in eutrophic
      coastal seas. The purposes of this study are to reveal adsorption characteristics
      of hydrogen sulfide onto crushed oyster shell, and to evaluate removal efficiency
      of hydrogen sulfide from pore water in organically enriched sediments using
      container experiment in order to develop a coastal sediment amendment. The
      crushed oyster shell was mainly composed of CaCO(3) with calcite and CaO crystal
      phase. The batch experiment showed removal kinetics of hydrogen sulfide can be
      expressed as the first order equation and Langmuir plot fitted well in describing
      the adsorption behavior with the adsorption maximum at 12 mg-S g(-1). The
      container experiments suggested the oyster shell adsorbs hydrogen sulfide in pore
      water effectively and reduces oxygen consumption in the overlying water.
      Furthermore, oxidation-reduction potential of the sediment was higher with
      addition of crushed oyster shell than the control without oyster shell. Thus, it
      is concluded that crushed oyster shell can be an effective amendment to remediate
      organically enriched sediments in eutrophic coastal seas.

PMID- 19394820
TI  - Effects of organic loading rates on the continuous electricity generation from
      fermented wastewater using a single-chamber microbial fuel cell.
AB  - Novel coupling of single-chamber microbial fuel cells (MFCs) with granular
      activated carbon anodes were constructed, and their ability to produce
      electricity from fermented wastewater operating in continuous mode was
      investigated. MFCs treating real fermented wastewater can generate a power
      density of approximately 1884 mW/m(3), which is equivalent to approximately 51.5%
      of that obtained from the MFCs (3664 mW/m(3)) using acetate at the same organic
      loading rate (OLR) of 1.92 g/Ld. As the OLR was increased in a stepwise fashion,
      power density increased to 2981 mW/m(3) at an OLR of 3.84 g/Ld. The corresponding
      energy production was 268 kJ/m(3)d. The decrease in the power density was mainly
      due to the higher internal resistance resulted from complex substrate. Based on
      the electrode characteristics, it was verified that colloidal particulates and
      complex organics in the real fermented wastewater not only lowered power density
      but also played a role as rate-limiting factors in the continuous generation of
      electricity.

PMID- 19394821
TI  - 3-(aminomethyl)piperazine-2,5-dione as a novel NMDA glycine site inhibitor from
      the chemical universe database GDB.
AB  - Docking of randomly selected compounds from the chemical universe database GDB
      11, which contains all organic molecules up to 11 atoms of C, N, O, F possible
      under consideration of simple chemical stability and synthetic feasibility rules,
      into the NMDA receptor glycine site (1pb7.pdb) lead to the identification of 3
      (aminomethyl)piperazine-2,5-dione 3 and its close analog 5
      (aminomethyl)piperazine-2,3-dione 4 as possible new ligands for this drug target,
      which is implicated in synaptic plasticity, neuronal development, learning and
      memory. Synthesis of these compounds in 4 and 6 steps, respectively, and testing
      by radioligand displacement assays and electrophysiological measurements in
      Xenopus oocytes show that while 4 is inactive, 3 is indeed an inhibitor of
      glycine, with an estimated K(D) of 50 microM.

PMID- 19394822
TI  - Inhibition of Pseudomonas aeruginosa quorum sensing by AI-2 analogs.
AB  - Autoinducer-2 (AI-2) has been suggested to serve as a universal interspecies
      quorum sensing signaling molecule. We have synthesized a set of AI-2 analogs with
      small incremental changes in alkyl substitution on C-2 and evaluated them for
      their agonistic and antagonistic potential as quorum sensing (QS) attenuators in
      two different bacterial species: Pseudomonas aeruginosa and Vibrio harveyi.
      Unexpectedly, several of the analogs were found to function as synergistic QS
      agonists in V. harveyi, while two of these analogs inhibit QS in P. aeruginosa.

PMID- 19394823
TI  - Discovery of N-aryl-9-oxo-9H-fluorene-1-carboxamides as a new series of apoptosis
      inducers using a cell- and caspase-based high-throughput screening assay. 1.
      Structure-activity relationships of the carboxamide group.
AB  - N-(2-Methylphenyl)-9-oxo-9H-fluorene-1-carboxamide (2a) was identified as a novel
      apoptosis inducer through our caspase- and cell-based high-throughput screening
      assay. Compound 2a was found to be active with sub-micromolar potencies for both
      caspase induction and growth inhibition in T47D human breast cancer, HCT116 human
      colon cancer, and SNU398 hepatocellular carcinoma cancer cells. It arrested
      HCT116 cells in G(2)/M followed by apoptosis as assayed by the flow cytometry.
      Structure-activity relationship (SAR) studies of the carboxamide group identified
      the lead compound N-(2-(1H-pyrazol-1-yl)phenyl)-9-oxo-9H-fluorene-1-carboxamide
      (6s). Compound 6s, with increased aqueous solubility, was found to retain the
      broad activity in the caspase activation assay and in the cell growth inhibition
      assay with sub-micromolar EC(50) and GI(50) values in T47D, HCT116, and SNU398
      cells, respectively.

PMID- 19394824
TI  - Total synthesis and determination of the absolute configuration of FD-838, a
      naturally occurring azaspirobicyclic product.
AB  - The first asymmetric total synthesis of FD-838, a naturally occurring
      azaspirobicyclic product, has been accomplished allowing determination of its
      absolute stereochemistry.

PMID- 19394825
TI  - Remote site extradural haematoma.
AB  - Postoperative extradural haematoma is a well described and serious complication
      of intracranial procedures that usually occurs at the site of the operation.
      Remote site extradural haematoma (that occurring distant to the site of the
      craniotomy) is relatively rare and may occasionally cause significant
      neurological morbidity or even death. We report this rare complication in an 18
      year-old male who underwent craniotomy for excision of recurrent left temporal
      ganglioglioma.

PMID- 19394826
TI  - Broken bioceramic used in a computer-assisted reconstruction of the frontal skull
      bone.
AB  - We report a complication occurring after the use of a bioceramic material for a
      three-dimensional reconstructive cranioplasty. A patient who had a satisfactory
      aesthetic result after frontal skull bone reconstruction with bioceramic injured
      his head after falling out of bed. The bioceramic material fragmented and the
      three fragments migrated over each other to form a lump. The bioceramic material
      had to be surgically removed. Care must be taken when using the fragile
      bioceramic material for reconstructive purposes, especially when patients are at
      risk of frequent falls.

PMID- 19394827
TI  - What lies beneath the tent? JC-virus cerebellar granule cell neuronopathy
      complicating sarcoidosis.
AB  - A 49-year-old, HIV-negative woman with sarcoidosis presented with a subacute
      unilateral cerebellar syndrome. A brain MRI revealed a hyperintense lesion
      without mass effect in the left cerebellar hemisphere, but no pathology above the
      tentorium. Steroid therapy for presumed neurosarcoidosis was ineffective and the
      patient deteriorated progressively. Cerebellar biopsy showed abnormal granule
      cells and demyelination. Immunocytochemistry confirmed the diagnosis of
      progressive multifocal leucoencephalopathy (PML) with JC (John Cunningham) virus
      granule cell neuronopathy. The patient succumbed to progressive brainstem
      dysfunction despite treatment with cidofovir. Although rare, PML should be
      considered in all patients with impaired cell-mediated immunity and unexplained
      neurological dysfunction, even in the absence of HIV infection.

PMID- 19394828
TI  - Neurocysticercosis: a review of current status and management.
AB  - Neurocysticercosis (NCC) is an infection of the brain and its coverings by the
      larval stage of the tapeworm Taenia solium. It is the most common helminthic
      infestation of the central nervous system and a leading cause of acquired
      epilepsy worldwide. NCC induces neurological syndromes that vary from an
      asymptomatic infection to sudden death. Neuroimaging is the mainstay of
      diagnosis. The diagnosis is suggested in patients living in endemic areas with
      typical CT scan findings and a compatible clinical picture. Since the late 1980s,
      successful medical treatment has been established with relatively short courses
      of either albendazole or praziquantel. The selection of cases for medical or
      surgical treatments has improved and these two forms of therapy are
      complementary. In general, indications of surgery are: cysts that compress the
      brain and cranial nerves locally, intracranial hypertension or edema refractory
      to medical treatment, intraventricular NCC, spinal NCC with cord or root
      compression and ocular cysts. Recently, endoscopic approaches for ventricular NCC
      have been developed, which are now the treatment of choice for ventricular NCC
      with hydrocephalus.

PMID- 19394829
TI  - 2-(substituted phenyl)amino analogs of 1-methoxyspirobrassinol methyl ether:
      synthesis and anticancer activity.
AB  - New analogs of indole phytoalexin 1-methoxyspirobrassinol methyl ether have been
      designed by replacement of its 2-methoxy group with 2-(substituted phenyl)amino
      group. Synthesized by spirocyclization methodology, trans- and cis
      diastereoisomers of target compounds were isolated and evaluated as potential
      anticancer and antimicrobial agents. Their molecular geometries were refined by
      ab initio minimizations. Pharmacophore modeling and QSAR studies were performed
      in order to correlate their molecular structure and biological activity.

PMID- 19394831
TI  - 2'-deoxy-1-methylpseudocytidine, a stable analog of 2'-deoxy-5-methylisocytidine.
AB  - 2'-deoxy-5-methylisocytidine is widely used in assays to personalize the care of
      patients infected with HIV, hepatitis C, and other infectious agents. However,
      oligonucleotides that incorporate 2'-deoxy-5-methylisocytidine are expensive,
      because of its intrinsic chemical instability. We report here a C-glycoside
      analog that is more stable and, in oligonucleotides, pairs with 2'
      deoxyisoguanosine, contributing to duplex stability about as much as a standard
      2'-deoxycytidine and 2'-deoxyguanosine pair.

PMID- 19394830
TI  - Mechanism-based inhibitors of serine proteases with high selectivity through
      optimization of S' subsite binding.
AB  - A series of mechanism-based inhibitors designed to interact with the S' subsites
      of serine proteases was synthesized and their inhibitory activity toward the
      closely-related serine proteases human neutrophil elastase (HNE) and proteinase 3
      (PR 3) was investigated. The compounds were found to be time-dependent inhibitors
      of HNE and were devoid of any inhibitory activity toward PR 3. The results
      suggest that highly selective inhibitors of serine proteases whose primary
      substrate specificity and active sites are similar can be identified by
      exploiting differences in their S' subsites. The best inhibitor (compound 16) had
      a k(inact)/K(I) value of 4580 M(-1)s(-1).

PMID- 19394832
TI  - Discovery and SAR of cinnolines/quinolines as liver X receptor (LXR) agonists
      with binding selectivity for LXRbeta.
AB  - A series of cinnolines/quinolines was prepared and it was found that 4-phenyl
      cinnoline/quinolines with either a 2',3' or 2',5'-disubstituted benzyloxy moiety
      or the 1-Me-7-indole methoxy moiety on the meta position of the 4-phenyl ring
      showed good binding selectivity for LXRbeta over LXRalpha. The LXRbeta binding
      selective modulators displayed good activity for inducing ABCA1 gene expression
      in J774 macrophage cell line and poor efficacy in the LXRalpha Gal4 functional
      assay. 26, 37 and 41 were examined for their ability to induce SREBP-1c gene
      expression in Huh-7 liver cell line and they were weak partial agonists.

PMID- 19394833
TI  - Synthesis of spirocyclic sigma1 receptor ligands as potential PET radiotracers,
      structure-affinity relationships and in vitro metabolic stability.
AB  - Several 3H-spiro[[2]benzofuran-1,4'-piperidines] bearing a p-fluorobenzyl residue
      at the N-atom and various substituents in position 3 of the benzofuran system
      were synthesized. The crucial reaction steps are the addition of a lithiated
      benzaldehyde derivative to the p-fluorobenzylpiperidone 5 and the BF(3).OEt(2)
      catalyzed substitution of the methoxy group of 2a by various nucleophiles.
      Structure-affinity relationship studies revealed that compounds with two protons
      (2d), a methoxy group (2a), and a cyano group (2e) in position 3 possess
      subnanomolar sigma(1) affinity (K(i)=0.18 nM, 0.79 nM, 0.86 nM) and high
      selectivity against the sigma(2) subtype. The metabolites of 2a, 2d, and 2e,
      which were formed upon incubation with rat liver microsomes, were identified.
      Additionally, the rate of metabolic degradation of 2a, 2d, and 2e was determined
      and compared with the degradation rate of the non-fluorinated spirocyclic
      compound 1. For the synthesis of the potential PET tracers [(18)F]2a and
      [(18)F]2e two different radiosynthetic approaches were followed.

PMID- 19394834
TI  - Unique behavior of 2,6-bis(bromomethyl)naphthalene as a highly active organic DNA
      crosslinking molecule.
AB  - Among 14 bis-halomethylated naphthalenes and quinolines, 2,6
      bis(bromomethyl)naphthalene was found to have highly active crosslinking activity
      on DNA. The unique behavior of high microbial mutagenicity, even though it had a
      low propensity to form double-strands in linearized plasmid DNA, suggested that
      it would offer a new seed, capable of forming intrastrand crosslinks similar to
      cisplatin. The electron withdrawal extent of the halogen atoms, the substitution
      patterns of two halomethyl groups, and the introduction of a nitrogen atom into
      the aromatic nucleus had remarkable effects on the activity of the molecule.

PMID- 19394835
TI  - New cross-sections for production of 103Pd; review of charged particle production
      routes.
AB  - Production cross-sections of (103)Ag obtained by irradiating (nat)Pd and (nat)Cd
      with 70 MeV protons are presented and compared with ALICE-IPPE model
      calculations. Production of (103)Ag is of interest for the generation of (103)Pd
      widely used in brachytherapy. The investigated energy range of the
      (103)Rh(d,2n)(103)Pd reaction was extended up to 40 MeV and the results were
      compared with the curves of ALICE-IPPE, EMPIRE-II and GNASH theoretical codes.
      Thick target yields were calculated. An overview and analysis of the most
      important charged particle induced production routes of (103)Pd is presented. An
      explanation of the apparent discrepancy in the activity measurements for (103)Rh
      based on X- or gamma-ray is given.

PMID- 19394836
TI  - Irradiation facility at the TRIGA Mainz for treatment of liver metastases.
AB  - The TRIGA Mark II reactor at the University of Mainz provides ideal conditions
      for duplicating BNCT treatment as performed in Pavia, Italy, in 2001 and 2003
      [Pinelli, T., Zonta, A., Altieri, S., Barni, S., Braghieri, A., Pedroni, P.,
      Bruschi, P., Chiari, P., Ferrari, C., Fossati, F., Nano, R., Ngnitejeu Tata, S.,
      Prati, U., Ricevuti, G., Roveda, L., Zonta, C., 2002. TAOrMINA: from the first
      idea to the application to the human liver. In: Sauerwein et al. (Eds.), Research
      and Development in Neutron Capture Therapy. Proceedings of the 10th International
      Congress on Neutron Capture Therapy, Monduzzi editore, Bologna, pp. 1065-1072].
      In order to determine the optimal parameters for the planned therapy and
      therefore for the design of the thermal column, calculations were conducted using
      the MCNP-code and the transport code ATTILA. The results of the parameter study
      as well as a possible configuration for the irradiation of the liver are
      presented.

PMID- 19394837
TI  - Extra-corporeal liver BNCT for the treatment of diffuse metastases: what was
      learned and what is still to be learned.
AB  - Almost eight years ago, in December 2001, we performed for the first time in the
      world thermal neutron irradiation on an isolated liver of a patient. The organ
      was affected by diffuse metastases of a colon carcinoma and had been previously
      loaded with a (10)B compound. In July 2003, the same procedure was applied again
      on a patient for the treatment of unresectable and incurable hepatic metastases
      of a carcinoma of the rectum. Both patients are dead at present. Now we can
      analyze in depth the clinical history of these patients and evaluate the
      effectiveness of this therapy. From this exciting experience we learned much, and
      we also found out about complications till then unknown, which need to be studied
      and addressed experimentally. Unfortunately we can base our conclusions just on
      the experience we had with these two patients. We could have been much more
      detailed and firm in our statements if the number of clinical cases was larger.
      The BNCT Pavia project has been suspended, but it is more than likely to resume
      in a short time. Good findings were many. The procedure is feasible; the original
      concept of complete immersion of the diseased liver in a homogeneous neutron
      field proved effective and winning. The tumor masses resulted completely necrotic
      and unknown metastases too appeared radically treated; healthy hepatic tissue was
      preserved from both morphological and functional points of view; no symptoms of
      cirrhosis appeared even four years after treatment. For the long term surviving
      patient, quality of life was excellent. Other findings require to be tackled in
      depth. The "post-irradiation syndrome" we observed in both patients, with
      identical symptoms and biochemical derangements, creates a dramatic--even though
      totally reversible--clinical condition, that is the probable cause of death for
      our second patient, suffering from cardiomyopathy, 33 days after treatment. For
      the first patient, recurrences were a late yet fatal complication, for which even
      a further surgical revision was ineffective. We offer some hypotheses about their
      origin and possible prevention.

PMID- 19394838
TI  - Selective uptake of p-boronophenylalanine by osteosarcoma cells for boron neutron
      capture therapy.
AB  - Osteosarcoma is the most common non-hematologic primary cancer type that develops
      in bone. Current osteosarcoma treatments combine multiagent chemotherapy with
      extensive surgical resection, which in some cases makes necessary the amputation
      of the entire limb. Nevertheless its infiltrative growth leads to a high
      incidence of local and distant recurrences that reduce the percentage of cured
      patients to less than 60%. These poor data required to set up a new therapeutic
      approach aimed to restrict the surgical removal meanwhile performing a radical
      treatment. Boron neutron capture therapy (BNCT), a particular radiotherapy based
      on the nuclear capture and fission reactions by atoms of (10)B, when irradiated
      with thermal neutrons, could be a valid alternative or integrative option in case
      of osteosarcoma management, thanks to its peculiarity in selectively destroying
      neoplastic cells without damaging normal tissues. Aim of the present work is to
      investigate the feasibility of employing BNCT to treat the limb osteosarcoma.
      Boronophenylalanine (BPA) is used to carry (10)B inside the neoplastic cells. As
      a first step the endocellular BPA uptake is tested in vitro on the UMR-106
      osteosarcoma cell line. The results show an adequate accumulation capability. For
      the in vivo experiments, an animal tumor model is developed in Sprague-Dawley
      rats by means of an intrafemoral injection of UMR-106 cells at the condyle site.
      The absolute amounts of boron loading and the tumor to normal tissue (10)B ratio
      are evaluated 2 h after the i.v. administration of BPA. The boron uptake by the
      neoplastic tissue is almost twice the normal one. However, higher values of boron
      concentration in tumor are requested before upholding BNCT as a valid therapeutic
      option in the treatment of osteosarcoma.

PMID- 19394839
TI  - Development of a new multi-modal Monte-Carlo radiotherapy planning system.
AB  - A new multi-modal Monte-Carlo radiotherapy planning system (developing code: JCDS
      FX) is under development at Japan Atomic Energy Agency. This system builds on
      fundamental technologies of JCDS applied to actual boron neutron capture therapy
      (BNCT) trials in JRR-4. One of features of the JCDS-FX is that PHITS has been
      applied to particle transport calculation. PHITS is a multi-purpose particle
      Monte-Carlo transport code. Hence application of PHITS enables to evaluate total
      doses given to a patient by a combined modality therapy. Moreover, JCDS-FX with
      PHITS can be used for the study of accelerator based BNCT. To verify calculation
      accuracy of the JCDS-FX, dose evaluations for neutron irradiation of a
      cylindrical water phantom and for an actual clinical trial were performed, then
      the results were compared with calculations by JCDS with MCNP. The verification
      results demonstrated that JCDS-FX is applicable to BNCT treatment planning in
      practical use.

PMID- 19394840
TI  - Prompt gamma emissions in the reaction 115In(n,gamma)116In for neutrons around
      the 1.45 eV absorption resonance.
AB  - The relative intensities of different gamma emissions produced after the reaction
      (115)In(n,gamma)(116)In were analyzed for the particular case of incident neutron
      energies around the 1.45 eV indium absorption resonance. For this purpose, a
      pulsed neutron source in combination with the time-of-flight method for selecting
      the incident neutron energy range was employed. For neutrons around the mentioned
      absorption resonance the prompt gamma spectrum was extended to energies below 273
      keV, and the intensities of gamma emissions not reported in the literature for
      epithermal neutrons were determined.

PMID- 19394841
TI  - Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a
      rat model of diffuse lung metastases.
AB  - In order for boron neutron capture therapy (BNCT) to be eligible for application
      in lung tumour disease, three fundamental criteria must be fulfilled: there must
      be selective uptake of boron in the tumour cells with respect to surrounding
      healthy tissue, biological effectiveness of the radiation therapy and minimal
      damage or collateral effects of the irradiation on the surrounding tissues. In
      this study, we evaluated the biological effectiveness of BNCT by in vitro
      irradiation of rat colon-carcinoma cells previously incubated in boron-enriched
      medium. One part of these cells was re-cultured in vitro while the other was
      inoculated via the inferior vena cava to induce pulmonary metastases in a rat
      model. We observed a post-irradiation in vitro cell viability of 0.05% after 8
      days of cell culture. At 4 months follow-up, all animal subjects in the treatment
      group that received irradiated boron-containing cells were alive. No animal
      survived beyond 1 month in the control group that received non-treated cells
      (p<0.001 Kaplan-Meier). These preliminary findings strongly suggest that BNCT has
      a significant lethal effect on tumour cells and post irradiation surviving cells
      lose their malignant capabilities in vivo. This radio-therapeutic potential
      warrants the investigation of in vivo BNCT for lung tumour metastases.

PMID- 19394842
TI  - Delayed wheat flag leaf senescence due to removal of spikelets is associated with
      increased activities of leaf antioxidant enzymes, reduced glutathione/oxidized
      glutathione ratio and oxidative damage to mitochondrial proteins.
AB  - Removal of reproductive 'sink' i.e. spikelets from wheat at anthesis delays the
      rate of flag leaf senescence. In this work, the antioxidant defense was studied
      in the flag leaf of Triticum aestivum cv. Kalyansona plants showing normal (S +
      plants) and delayed senescence via removal of spikelets (S- plants). This was
      done by measurement of metabolites and activities of enzymes such as superoxide
      dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase,
      monodehydroascorbate reductase, dehydroascorbate reductase and glutathione
      reductase. S- plants had higher reduced glutathione/oxidized glutathione
      (GSH/GSSG) ratio and antioxidant enzyme activities than the control plants and
      the differences were apparent from 21 days after anthesis (DAA). The removal of
      the reproductive sink led to an increased antioxidant defense which may be
      contributing towards the delayed flag leaf senescence in wheat. Chloroplasts and
      mitochondria, important sources of ROS, were isolated at two stages representing
      early (7 DAA) and late (21 DAA) senescence. Oxidative damage to proteins was
      studied in these organelles in relation to SOD and APX. Mitochondria had higher
      levels of damaged proteins than chloroplasts at 7 DAA in both S+ and S- plants.
      Higher damage was related to the lower antioxidant enzyme levels of SOD and APX
      in mitochondria as compared to chloroplasts.

PMID- 19394843
TI  - Arterial cannulation for acute type A aortic dissection.

PMID- 19394845
TI  - A huge ascending aortic aneurysm bigger than the heart size.

PMID- 19394846
TI  - Bone marrow laser revascularisation for treating refractory angina due to diffuse
      coronary heart disease.
AB  - To increase the angiogenic response and clinical efficacy of TMR, the potential
      synergy and safety of combining TMR with concentrated autologous bone marrow
      derived stem cells was evaluated. Fourteen patients with diffuse coronary artery
      disease and medically refractory class III/IV angina who were not candidates for
      conventional therapies were treated using TMR in combination with intramyocardial
      injection of concentrated stem cells. At the time of surgery, autologous bone
      marrow (120 cc) was aspirated from the iliac crest and processed over 15 min into
      20 cc of concentrated mononuclear cells using a centrifugal system (HARVEST,
      Boston, MA). A single device performed holmium: YAG:TMR (CardioGenesis, Irvine,
      CA) with injection of 1 cc of concentrated stem cells through three multi-holed
      needles into the border zone around each laser channel. There were no
      perioperative adverse events including no arrhythmias. Mean number of injected
      cells per milliliter were: total mononuclear cells (81.3 x 10(6)), CD34(+) cells
      (0.6 x 10(6)), and CD133(+) cells (0.37 x 10(6)). At 7 months mean follow-up
      average angina class was significantly improved (3.5+/-0.5 vs 1.4+/-0.5;
      p=0.004). There was no death during the follow-up. Efficient delivery of stem
      cells combined with TMR in a single device seems to be safe and effective for
      treating unmanageable angina.

PMID- 19394847
TI  - Aortic regurgitation and coronary malperfusion secondary to intimo-intimal
      intussusception into the left ventricle in acute aortic dissection.

PMID- 19394848
TI  - Use of titanium plates in repair of adult complete sternal cleft.

PMID- 19394849
TI  - Predictors of impaired neurodevelopmental outcomes at one year of age after
      infant cardiac surgery.
AB  - OBJECTIVE: For most newborns, congenital heart defects (CHD) appear to be
      isolated anomalies and the brain is presumed to have normal developmental
      potential. Most studies of neurodevelopmental outcomes have focused on operative
      management strategies. METHODS: Infants with complex CHD and no identified
      syndromes other than 22q11 microdeletions enrolled in a study of apolipoprotein E
      (APOE) polymorphisms and developmental outcome were evaluated at one year of age;
      including genetic evaluation and the Bayley Scales of Infant Development-II
      [mental (MDI) and psychomotor developmental indices (PDI)]. RESULTS: Five hundred
      and fifty infants enrolled and 359 (20 with 22q11) of 501 survivors (72%)
      returned. Mean MDI was 90+/-15 and PDI was 78+/-18. Genetic syndromes not
      identified at birth were confirmed in 28 (8.1%) and suspected in 51 (15.0%). By
      multivariable analysis, suspected/confirmed genetic syndromes and APOE
      varepsilon2 allele predicted lower MDI and PDI, all p<0.04. Lower birth weight
      (p<0.001) and preoperative intubation (p=0.012) predicted lower MDI. Higher
      hematocrit during the initial operation was associated with higher MDI (p=0.007).
      Longer postoperative length of stay was predictive of lower PDI (p=0.002).
      Additional operations with cardiopulmonary bypass were associated with lower MDI
      and PDI (both p<0.002), but use of deep hypothermic circulatory arrest was not.
      CONCLUSIONS: Patient factors (birth weight and preoperative status) are
      significant determinants of neurodevelopmental outcomes as opposed to operative
      management strategies. In this cohort, genetic syndromes unsuspected at birth
      were surprisingly common and correlate with poor neurodevelopmental outcomes.
      Without multiple congenital anomalies, syndromes may be missed in infancy.
      Genetic evaluation should be considered in all infants with CHD.

PMID- 19394850
TI  - Constrictive pericarditis, still a diagnostic challenge: comprehensive review of
      clinical management.
AB  - The diagnosis of constrictive pericarditis (CP) continues to be a challenge in
      the modern era. Understanding the pathophysiology and integrating the results of
      invasive and non-invasive techniques are important in the differential diagnosis
      of CP and e.g. restrictive cardiomyopathy. New echocardiographic techniques such
      as tissue Doppler imaging (TDI) and 2D-speckle tracking, dual-source CT (computed
      tomographic imaging) and especially tagged cine-MRI (magnetic resonance imaging)
      with the analysis of phase contrast angiography sequences are promising novel
      approaches. Pericardiectomy in experienced centers with complete decortication
      (if technically feasible) is the treatment of choice for CP and it results in
      symptomatic relief in most patients. However, some patients may not benefit from
      pericardiectomy and this may be due to myocardial compliance abnormalities,
      myocardial atrophy after prolonged constriction, residual constriction or other
      myocardial processes. An important predictor of long-term outcome after
      pericardiectomy is the etiology of the pericardial disease. The overall mortality
      in the current literature is nearly 5-6%. Survival with post-surgical CP is worse
      than with idiopathic CP, but significantly better than with post-radiation CP.

PMID- 19394851
TI  - Surgical ventricular restoration combined with mitral valve procedure for
      endstage ischemic cardiomyopathy.
AB  - OBJECTIVE: A poor functioning dilated left ventricle with mitral regurgitation is
      the worst condition in chronic ischemic heart failure. Our 7-year experience in
      combined mitral valve and left ventricular reconstruction was evaluated.
      MATERIALS AND METHODS: Among 246 patients having undergone a left
      ventriculoplasty for postinfarction left ventricular dysfunction in our
      experience, there were 76 patients with advanced heart failure due to dilated
      ischemic cardiomyopathy with mitral regurgitation (70 males and 6 females with a
      mean age of 60 years). All patients had NYHA class III (n = 41) or IV (n = 35)
      heart failure, including 26 patients (34%) with inotropic support before the
      operation. All patients had a mitral regurgitation of more than 2+ and 46
      patients (61%) had 3+ or more. Mitral reconstruction (61 repairs, 15
      replacements) and left ventriculoplasty (Dor 34, SAVE 36, PLV 6) were undergone
      in combination with CABG (74%). RESULTS: Operative mortality was 7.9% (5.0% in 60
      elective and 18.8% in 16 emergency operations). The ejection fraction and cardiac
      index increased from 24.9 +/- 7.0% to 33.3 +/- 8.7%, and 2.0 +/- 0.4 l/min/m2 to
      2.6 +/- 0.4 l/min/m2, respectively (p < 0.001). The endodiastolic and
      endosystolic volume indices, and diastolic dimension decreased from 165.9 +/-
      43.2 ml/m2 to 121.2 +/- 31.1 ml/m2, 123.3 +/- 38.9 ml/m2 to 74.0 +/- 27.5 ml/m2,
      and 69.5 +/- 7.7 mm to 61.2 +/- 7.1 mm, respectively (p < 0.001). Late deaths
      were noted in 13 patients (17.1%), with 10 cardiac deaths. One- and 5-year
      survival rates were 80.2% and 67.7%, respectively. The mean NYHA class improved
      from 3.5 to 1.4 among the survivors. Multivariate analysis showed that patients
      with a mitral regurgitation of 3+ or more and preoperative endosystolic volume
      index were significant predictors for postoperative mortality. However, age,
      preoperative inotropes and pulmonary hypertension did not show any significant
      differences. CONCLUSION: Combined mitral and left ventricular reconstruction is
      effective in treating advanced heart failure with endstage ischemic
      cardiomyopathy associated with a dilated left ventricle and mitral regurgitation.

PMID- 19394852
TI  - Pediatric tracheal reconstruction with pericardial patch and strips of autologous
      cartilage.
AB  - OBJECTIVE: To analyze the results of pediatric tracheal reconstruction with
      autologous pericardial patch and strips of cartilage. METHODS: From September
      2003 to February 2008 14 non-consecutive children were operated using pericardial
      patch augmentation of the trachea combined with external reinforcement with
      strips of autologous cartilage. Thin semicircular strips were fashioned from
      costal arch cartilage. Associated vascular rings, slings and aberrantly coursing
      arteries were treated first. Cardiopulmonary bypass was used in all.
      Intraoperative tracheobronchoscopy was done in all. Postoperative bronchoscopies
      were performed at different time points. A retrospective analysis of patient
      records, surgical reports, tracheobronchoscopies, echocardiographic studies and
      CT scans was performed. Pre- and postoperative trachea cross-sectional areas were
      digitally measured and compared to cricoid cross-sectional areas in six patients.
      A paired t-test was used to make comparisons. RESULTS: Median age at operation
      was 21.3 (range 2.5-85) months. Ten patients were female. Four had associated
      surgery for cardiac anomalies. Double aortic arch (8), pulmonary artery sling
      (2), and aberrant origin of brachiocephalic artery (1) were concomitantly
      treated. Two patients had pulmonary agenesis. One patient had stenosis due to
      systemic inflammatory disease. Median follow-up was 27 (1-53) months. Late
      mortality occurred in one patient with pulmonary agenesis. One patient was
      reoperated and two bronchoscopies were done to remove granulation tissue. Median
      postoperative ventilation time was 5.5 (3-12) days with the exception of patients
      with pulmonary agenesis. Mean preoperative cross-sectional area was 29.4 +/-
      22.5% of the lumen at cricoid level. At last bronchoscopy this had increased to
      65.0 +/- 12.5% (p = 0.0001). To evaluate the stability of the reconstructed
      trachea, we compared the mean luminal areas at inspiration and expiration. No
      difference was observed (p = 0.13). One patient remains with mild stridor at
      exercise; all others have no respiratory symptoms. CONCLUSION: A stable wide
      trachea can be obtained in the great majority of cases, including whole length
      tracheal obstructions with complete circular rings. The technique is safe and
      reproducible with short intensive care stay and good mid-term results. Growth of
      the reconstructed trachea appears to be unrestricted.

PMID- 19394854
TI  - The impact of the lung allocation scoring system at the single national Veterans
      Affairs Hospital lung transplantation program.
AB  - OBJECTIVE: The lung allocation score (LAS) has changed the distribution of donor
      lungs for transplantation. This study was undertaken to evaluate the impact of
      the LAS on a unique patient population undergoing lung transplantation (LTX) at
      the single national Veterans Affairs (VA) LT center. METHODS: One hundred and ten
      consecutive VA patients underwent LTX between 1994 and 2007. Patients
      transplanted using the LAS (LAS, n=26) were compared to patients transplanted
      prior to introduction of the LAS (pre-LAS, n=84). RESULTS: Waiting time decreased
      from 353.8+/-254.7 (pre-LAS) to 238.0+/-306.6 (LAS) days (p<0.01). Recipient
      diagnoses have changed with an increase in idiopathic pulmonary fibrosis [11%
      (9/84) pre-LAS vs 46% (12/26) LAS, p<0.01] and a decrease in emphysema [57%
      (48/84) pre-LAS vs 35% (9/26) LAS, p<0.01]. Mean LAS calculation was 33.1+/-2.9
      for pre-LAS versus 41.9+/-9.8 for the LAS (p<0.01). Postoperative complications
      did not differ between the groups. Length of hospital stay decreased from 44.3+/
      42.9 (pre-LAS) to 18.1+/-12.3 (LAS) days (p<0.01). Hospital mortality and 1-year
      survival did not differ between the pre-LAS and LAS groups (7% vs 8%; p=0.72 and
      92% [95% confidence interval (CI) 86-98] vs 92% [CI 82-100]; p=0.23,
      respectively). CONCLUSIONS: The LAS appears to be achieving its objectives by
      reducing waitlist time and altering the distribution of lung disease being
      transplanted on the basis of medical necessity in the U.S. VA population. In
      addition, the LAS does not appear to have adversely affected short-term post
      transplant outcomes in our recipient cohort.

PMID- 19394855
TI  - Presystolic mitral annular septal-lateral shortening is independent from left
      atrial and left ventricular contraction during acute volume depletion.
AB  - BACKGROUND: The mitral annulus (MA) is a dynamic structure that joins the left
      atrium (LA) and left ventricle (LV), but it is unknown whether MA motion is
      coupled to the LA or the LV or neither of the two. Since a well orchestrated
      coordination of LA, MA and LV septal-lateral (S-L) dynamics is essential for
      efficient valve closure, we assessed their functional coupling in an experimental
      ovine model. To assess the coupling under a wide range of physiological
      conditions, data were acquired in normal and acutely volume depleted hearts.
      METHODS: In 10 sheep, radiopaque markers were placed in LA, MA and LV base
      (LVbase). Twelve weeks postoperatively, 4-D marker coordinates were obtained by
      stereo videofluoroscopy (60 frames/s) before (CTRL) and during acute inferior
      vena caval occlusion (VCO). Septal-lateral dimensions were calculated as
      distances between corresponding marker pairs in the LA, MA and LVbase 5 frames
      before end-diastole (ED-84 ms) and at end-diastole. Dynamics during late diastole
      are described as changes from ED-84 ms versus end-diastole. To study the
      functional coupling between LA, MA and LVbase we calculated slopes during late
      diastole from simple linear regressions on an animal-by-animal basis. RESULTS:
      During late diastole in CTRL, the LA and MA both shortened along the S-L
      dimension (32.9 +/- 6.6 mm vs 31.0 +/- 5.5 mm, p = 0.026 and 27.3 +/- 3.7 mm vs
      24.6 +/- 4.1 mm, p = 0.005, respectively) whereas the LVbase lengthened (56.2 +/-
      9.3 mm vs 57.3 +/- 9.3 mm, p = 0.012). VCO abolished septal-lateral dynamics of
      LA and LVbase during late diastole (27.8 +/- 4.3 mm vs 27.4 +/- 3.9 mm, p = 0.155
      and 49.4 +/- 7.7 mm vs 49.5 +/- 7.5 mm, p = 0.752, respectively) while the MA
      still shortened (19.0 +/- 2.9 vs 18.0 +/- 2.8, p = 0.042). Under CTRL conditions
      LA dynamics were linearly dependent from MA dynamics (average coefficient 0.57, p
      = 0.001), suggesting that LA and MA are functionally coupled. With acute volume
      depletion, MA dynamics were linearly independent from both, LA and LV (average
      coefficient 0.28, p = 0.159 and 0.58, p = 0.192, respectively). CONCLUSION:
      Whereas MA and LA dynamics are coupled during late diastole in hearts with normal
      LV volumes, presystolic mitral annular septal-lateral shortening is independent
      from LA and LV dynamics with acute volume depletion. A better understanding of
      mitral annular dynamics and their functional coupling may help improve mitral
      valve repair strategies.

PMID- 19394856
TI  - Donor cardiac troponin-I: a biochemical surrogate of heart function.
AB  - OBJECTIVE: Cardiac troponin-I (cTnI) levels in the potential heart transplant
      donor may be a marker of heart dysfunction and predictive of recipient outcome.
      We studied the prevalence of cTnI elevation, its association with heart function
      and usability and its relationship with the time duration from coning. METHODS:
      In a prospective study, cTnI measurement, Swan-Ganz catheterisation and
      transthoracic echocardiography were performed at initial assessment in 79
      potential heart donors (mean age 43 +/- 13.1 years). All donors were then managed
      according to a strict algorithm to optimise cardiac function, some receiving
      hormonal therapy as part of a randomised trial. Donor heart suitability for
      transplantation was assessed after 7 h of management. The association of cTnI
      with initial functional indices was assessed and outcome compared for donors
      categorised according to cTnI level < or = 1 microg l(-1) or >1 microg l(-1).
      RESULTS: Serum cTnI levels negatively correlated with initial cardiac index (CI)
      (p = 0.003), right (p < 0.001) and left ventricular ejection fraction (p = 0.001)
      and positively with LV Tei index (p = 0.003). Serum cTnI was >1 microg l(-1) in
      29/79 donors. Higher CVP (10 +/- 5.1 vs 7.9 +/- 2.9; p = 0.026) and PAWP (12 +/-
      5.4 vs 8.1 +/- 3.1; p = 0.002), lower cardiac index (2.7 +/- 1.1 vs 3.6 +/- 0.9;
      p = 0.001) and fractional shortening (p < 0.01) and worse wall motion score index
      (p < 0.01) were observed in the cTnI >1 microg l(-1) group. CTnI and functional
      markers correlated with the time duration from coning. CONCLUSION: The donor cTnI
      level represents a biochemical surrogate of functional donor heart assessment.
      High cTnI is associated with worse donor heart function and may act as a prompt
      for detailed assessment and optimisation.

PMID- 19394857
TI  - Coronary artery bypass grafting versus drug-eluting stents in multivessel
      coronary disease. A meta-analysis on 24,268 patients.
AB  - OBJECTIVE: Coronary artery bypass grafting (CABG) has been shown to provide
      better results than percutaneous coronary intervention (PCI) in multivessel
      coronary disease. Drug-eluting stents (DES) have significantly improved results
      of PCI in terms of restenosis but the advantages of such a treatment compared to
      CABG remain uncertain. This meta-analysis summarizes available data from
      observational cohorts comparing DES-PCI versus CABG. METHODS: We performed a
      systematic literature search for observational cohorts comparing CABG versus DES
      PCI in patients with multivessel coronary disease. The mixed model method was
      used to obtain the pooled hazard ratio (HR) for outcomes of interest. RESULTS: A
      total of nine observational nonrandomized studies were identified and analyzed
      including a total of 24,268 patients with multivessel coronary disease who
      underwent DES-PCI (n=13,540) and CABG (n=10,728). Mean follow-up time was 20
      months. Pooled analysis showed that DES-PCI and CABG were comparable in terms of
      composite occurrence of death, acute myocardial infarction and cerebrovascular
      accidents (HR=0.94; 95% CI=0.72-1.22; p=0.66). However, there was a significantly
      higher risk of repeat revascularization in the DES-PCI group (HR=4.06; 95%
      CI=2.64-6.24; p<0.001). Overall major adverse cardiac and cerebrovascular events
      rate in the DES-PCI was higher compared to the CABG group (HR=1.86; 95% CI=1.36
      2.54; p<0.001). CONCLUSIONS: In the 'real world' clinical practice, overall major
      adverse cardiac and cerebrovascular events rate continues to be higher after DES
      PCI due to an excess of redo revascularization compared with CABG.

PMID- 19394858
TI  - Off-pump transapical mitral valve replacement.
AB  - OBJECTIVE: Percutaneous valve replacement was recently introduced, and reports of
      early clinical experience have already been published. To date, this technique is
      limited to the replacement of pulmonary and aortic valves in a strictly selected
      group of patients. The aim of this study was to analyse a self-expanding valved
      stent for minimally invasive replacement of the mitral valve in animals. METHODS:
      A newly designed nitinol stent was specially designed for this experimental acute
      study. It comprised of a left ventricular tubular stent with star shaped left
      atrial anchoring springs and carried a trileaflet bovine pericardial valve. A
      polytetrafluoroethylene membrane was sutured to envelop the atrial springs and
      the outside of the ventricular stent. The ventricular anchoring system was the
      same as in our previously reported results with a similar mitral valved stent.
      Seven pigs underwent minimally invasive off-pump mitral valved stent
      implantation. This was performed through a lower mini-sternotomy and a standard
      transapical approach under transoesophageal echocardiographic (TEE) guidance was
      used. RESULTS: The valved stent is fully retrievable and precise deployment and
      accurate adjustment of its intra-annular position is achievable to eliminate
      paravalvular leakage. The deployment time ranged from 127 to 255s and the blood
      loss from 70 to 220cc. One animal died of intractable ventricular fibrillation.
      Mitral regurgitation in all surviving animals was minimal (trace in 5/6 and mild
      in 1/6 during echo examination; on the contrast ventriculogram no mitral
      insufficiency was observed except in one documented as mild paravalvular
      regurgitation). These animals remained haemodynamically stable (6/6) and without
      TEE or ventriculographic changes for 1h. CONCLUSION: Implantation of a tricuspid
      bovine pericardial valved stent in the mitral position is feasible in pigs
      through a transcatheter approach. This was possible through a smaller delivery
      system than previously reported. Additional studies are required to demonstrate
      long-term feasibility, durability, and heart function.

PMID- 19394859
TI  - What is the evidence for gender differences in ferritin and haemoglobin?
AB  - Reference ranges for haemoglobin and ferritin in women of reproductive age are
      widely reported showing values that are lower than equivalent aged males. Similar
      values would be expected in the absence of different biological requirements.
      While reference ranges have been derived from data on large populations, it is
      likely that these populations have included significant numbers of women who are
      iron deficient in view of menstrual blood loss and poor dietary intake.
      Populations with a daily iron intake in excess of 100mg have shown that iron
      deficiency in females is rare. Studies reporting bone marrow with iron stains
      from 50 years ago pointed out that significant numbers of women were iron
      deficient and more recently serum ferritin studies have confirmed this. However,
      a large number of women in the Western world spend a significant part of their
      lives in a negative iron balance due to a combination of poor diet and menstrual
      blood loss. The presence of haem iron in the diet of humans enhances non-haem
      iron absorption but dietary surveys consistently report that women's diet is
      deficient in iron. Furthermore, the typical Western diet contains many common
      foods that limit iron absorption. It appears that lower haemoglobin and ferritin
      values in menstruating women have been accepted as normal rather than possibly
      representing widespread iron deficiency. Reference ranges should be re-evaluated
      in populations proven to be iron replete.

PMID- 19394860
TI  - A novel ion trap that enables high duty cycle and wide m/z range on an orthogonal
      injection TOF mass spectrometer.
AB  - Although TOF analyzers with orthogonal ion injection provide the whole spectrum
      without scanning, their duty cycle is low compared with scanning analyzers in
      single ion monitoring mode. Typical duty cycle is in the range of 5% to 30%
      depending on the instrument geometry and ion m/z value. We present here a novel
      trapping/releasing setup, which offers the duty cycle near 100% over a wide
      range. Operation in the mass range from m/z 120 to almost 2000 is demonstrated.
      Ions are trapped in a short linear ion trap at the end of the collision cell in
      an axial pseudopotential well created by additional rf ("AC") voltage applied to
      all four rods of the trap with the same amplitude and phase. The pseudopotential
      created by AC field is mass dependent, and by ramping down the AC voltage, ions
      can be released from the trap sequentially from high m/z to low, while all ions
      are gaining the same kinetic energy. Upon entering the TOF accelerator, ions with
      lower m/z catch up with heavier ions, and the AC ramp parameters can be selected
      to make all ions meet in the center of the TOF extraction region, resulting in
      sensitivity gains from 3 to 14 without loss of mass accuracy or resolution.

PMID- 19394861
TI  - The cotton rat model of respiratory viral infections.
AB  - Development of successful vaccines against human infectious diseases depends on
      using appropriate animal models for testing vaccine efficacy and safety. For some
      viral infections the task is further complicated by the frequently changing
      genetic make-up of the virus, as in the case of influenza, or by the existence of
      the little-understood phenomenon of vaccine-enhanced disease, as in the case of
      respiratory syncytial virus (RSV). The cotton rat Sigmodon hispidus has been used
      for years as an excellent small animal model of the RSV vaccine-enhanced disease.
      Recently, using cotton rats, we have demonstrated that vaccination against
      another paramyxovirus, human metapneumovirus (hMPV), can also lead to vaccine
      enhanced disease. In addition to the study of paramyxoviruses, S. hispidus
      presents important advantages for the study of orthomyxoviruses such as
      influenza. The cotton rat is susceptible to infection with unadapted human
      influenza strains, and heterosubtypic immunity to influenza can be evoked in S.
      hispidus. The mechanisms of influenza, RSV, and hMPV pathogenesis and immunity
      can now be investigated in the cotton rat with the development of species
      specific reagents for this animal model.

PMID- 19394862
TI  - Comparison of regression models for the analysis of fall risk factors in older
      veterans.
AB  - PURPOSE: To compare the performance of eight regression models for analyzing risk
      of falling, focusing on the effect of physical inactivity in older veterans.
      METHODS: This study uses data from a fall risk factor screening and modification
      trial in community-dwelling Canadian male veterans of World War II or the Korean
      War, with falls ascertained prospectively using calendars and physical activity
      (PA) measured at baseline with a single global question. The effect of PA on
      falling was assessed using eight different multivariable regression models, with
      three models treating falling as a non-recurrent event whereas the other five
      models regard falls as recurrent events. RESULTS: Recurrent event models showed
      that male veterans who reported being less active than their peers were 1.42
      (1.02-1.97) to 2.46 (1.18-5.14) times more likely to fall than those who reported
      being about as or more active than their peers (n = 270; mean age +/- SD = 81.1
      +/- 4.0 years). None of the non-recurrent event models detected a statistically
      significant association between PA and falls. CONCLUSIONS: Risk of falling may be
      better analyzed using regression models for recurrent events. These results have
      important implications for the collection and analysis of fall outcome data.

PMID- 19394863
TI  - Contraceptive choices of women 35-44 years of age: findings from the behavioral
      risk factor surveillance system.
AB  - PURPOSE: With an estimated 3.1 million unintended pregnancies in the United
      States each year, patterns of contraceptive use have significant public health
      importance. Little literature has focused on these patterns in women over age 35.
      METHODS: Using data from the 2004 Behavioral Risk Factor Surveillance System, we
      conducted a population-based analysis of 22,890 women between the ages of 35-44
      years who completed information on family planning. Lifestyle, demographic, and
      medical history covariates were assessed and multinomial logistic regression was
      used to obtain odds ratios (OR) and 95% confidence intervals (CI). RESULTS:
      Female sterilization was the most popular contraceptive method among women aged
      35-44 years (28.5%). Relative to non-Hispanic white women, Hispanic and non
      Hispanic black women were less likely to use effective methods of contraception
      such as male sterilization (OR = 0.33, 95% CI: 0.23, 0.46; and OR = 0.10, 95% CI:
      0.06, 0.16, respectively) and oral contraceptives (OR = 0.55, 95% CI: 0.41, 0.73;
      and OR = 0.42, 95% CI: 0.31, 0.57, respectively) after adjustment for
      demographic, lifestyle, and medical factors. CONCLUSIONS: Although fecundity is
      reduced in women of this age group, increased rates of maternal and fetal
      complications make unintended pregnancies riskier. This study demonstrates
      opportunities for targeted counseling and increased awareness of the diversity of
      contraceptive choices for older women.

PMID- 19394864
TI  - Alcohol consumption and risk of hematologic malignancies.
AB  - PURPOSE: Limited data suggest that alcohol drinking may have an inverse relation
      to risk of non-Hodgkin's lymphoma (NHL). Prospective data about alcohol, NHL, and
      other hematologic malignancies (HM) are sparse. METHODS: We carried out a cohort
      study in a multiethnic population of 126,293 adults who supplied baseline
      information at health examinations. There were subsequent HM diagnoses in 1244
      persons. We used Cox proportional hazards models with seven covariates. The role
      of beverage types was studied by comparing groups with preponderant choices and
      by studying the role of frequency of drinking beverage types. RESULTS: Using
      lifelong abstainers plus infrequent drinkers as referent, adjusted relative risks
      (95% confidence intervals) for HM follow: less than one drink per day=1.0 (0.9
      1.2), one to two drinks per day=0.9 (0.7-1.0), greater than three drinks per
      day=0.7 (0.6-0.9, p=0.008). For 673 NHL these were 1.2 (1.0-1.5), 0.9 (0.7-1.2),
      and 0.9 (0.6-1.2). Persons reporting greater than three drinks/day had inverse
      relations to lymphocytic (n= 146) and myelocytic (n= 169) leukemias, with
      relative risk of 0.5 (0.2-1.0, p<0.05) for each. No major independent relation
      was seen for choice of wine, liquor, or beer. CONCLUSIONS: Alcohol drinking is
      associated with slightly lower risk of HM, due largely to inverse relations to
      lymphocytic and myelocytic leukemia.

PMID- 19394865
TI  - Understanding the reasons why mothers do or do not have their adolescent
      daughters vaccinated against human papillomavirus.
AB  - PURPOSE: The objective of this study was to compare the reasons why mothers do or
      do not have their adolescent daughters vaccinated against HPV. METHODS: Mothers
      of vaccinated and unvaccinated 11- to 17-year-old girls seen during preventive
      care visits in outpatient family medicine or pediatric clinics underwent an
      audiotaped structured telephone interview that used open-ended questions to
      assess the reasons underlying maternal decisions about HPV vaccination.
      Qualitative methods categorized maternal responses into themes. RESULTS:
      Interviews of 52 mothers (19 declining vaccination, 33 accepting) identified
      several distinct factors underlying their decisions about HPV vaccination. Lack
      of knowledge about HPV, age-related concerns, and low perceived risk of infection
      were commonly cited reasons for declining vaccination. Desire to prevent illness,
      physician recommendation, and a high perceived risk of infection were commonly
      identified motivating factors. Both groups of mothers had significant concerns
      about vaccine safety. Locus of control (e.g., mother or daughter) of health
      related decisions arose as a novel factor influencing this decision that had not
      been previously described in the context of HPV vaccination. CONCLUSIONS:
      Addressing safety concerns, educating parents about the age-specific risk of HPV
      infection, and promoting strong physician recommendation for vaccination may be
      the most useful targets for future interventions to increase HPV vaccine
      utilization.

PMID- 19394866
TI  - Copy number variants of GSTM1 and GSTT1 in relation to lung cancer risk in a
      prospective cohort study.
AB  - PURPOSE: Previous studies did not discriminate wild-type from hemizygous
      genotypes of GSTM1 and GSTT1. In this study, we investigated wild-type,
      hemizygous deletion, and homozygous deletion genotypes of GSTM1 and GSTT1 and
      lung cancer risk. METHODS: We conducted a nested case-control study of 143
      primary incident lung cancer cases matched to 447 cancer-free controls.
      Genotyping was carried out using a real-time polymerase chain reaction (PCR)
      based assay. Conditional logistic regression models were used to estimate odds
      ratios (OR) and 95% confidence intervals (CI). RESULTS: Compared to GSTM1 wild
      type carriers, the relative odds of lung cancer increased from 1.49 (95% CI=0.66
      3.40) to 1.80 (95% CI=0.81-4.02) for the hemizygous and homozygous deletion
      genotypes, respectively (p-trend=0.13). The strongest associations were seen
      among those who smoked less than one pack per day and had greater than or equal
      to one deletion variant of GSTM1 (OR=3.25; 95% CI=0.93-11.34; p-trend=0.07)
      whereas the reverse was observed for smokers who smoked greater than or equal to
      one pack per day (OR=0.80; 95% CI=0.24-2.67; p-interaction=0.08). No clear
      associations were observed for GSTT1 genotypes. CONCLUSIONS: Risk of lung cancer
      increased as the number of deletion variants increased for GSTM1, although the
      associations were nonsignificant. Discriminating between the wild-type,
      hemizygous, and homozygous deletion GSTM1 genotypes permitted a more precise
      characterization of the associations between GSTM1 deletion variants and lung
      cancer.

PMID- 19394867
TI  - MVC techniques to normalize trunk muscle EMG in healthy women.
AB  - Normalization of the surface electromyogram (EMG) addresses some of the inherent
      inter-subject and inter-muscular variability of this signal to enable comparison
      between muscles and people. The aim of this study was to evaluate the
      effectiveness of several maximal voluntary isometric contraction (MVC)
      strategies, and identify maximum electromyographic reference values used for
      normalizing trunk muscle activity. Eight healthy women performed 11 MVC
      techniques, including trials in which thorax motion was resisted, trials in which
      pelvis motion was resisted, shoulder rotation and adduction, and un-resisted MVC
      maneuvers (maximal abdominal hollowing and maximal abdominal bracing). EMG
      signals were bilaterally collected from upper and lower rectus abdominis, lateral
      and medial aspects of external oblique, internal oblique, latissimus dorsi, and
      erector spinae at T9 and L5. A 0.5s moving average window was used to calculate
      the maximum EMG amplitude of each muscle for each MVC technique. A great inter
      subject variability between participants was observed as to which MVC strategy
      elicited the greatest muscular activity, especially for the oblique abdominals
      and latissimus dorsi. Since no single test was superior for obtaining maximum
      electrical activity, it appears that several upper and lower trunk MVC techniques
      should be performed for EMG normalization in healthy women.

PMID- 19394868
TI  - Consensus guidelines for periprocedural management of coagulation status and
      hemostasis risk in percutaneous image-guided interventions.

PMID- 19394869
TI  - Cardiopulmonary bypass increases endogenous carbon monoxide production.
AB  - OBJECTIVE: Endogenous carbon monoxide (CO) production results from heme
      metabolism catalyzed by heme oxygenase (HO) enzymes of which HO-1 is inducible by
      oxidative stress. Cardiopulmonary bypass provokes oxidative stress associated
      with systemic and pulmonary inflammatory responses. Therefore, the authors
      hypothesized that cardiopulmonary bypass is associated with an increase in
      endogenous carbon monoxide production. DESIGN: A prospective, observational
      study. SETTING: A cardiothoracic operating room. PARTICIPANTS: Forty patients
      undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: End-tidal CO levels and arterial carboxyhemoglobin
      concentrations were measured before and after cardiopulmonary bypass. End-tidal
      CO concentrations and carboxyhemoglobin levels were increased significantly after
      cardiopulmonary bypass as compared with prebypass values (median [interquartile
      range]: end-tidal CO levels: 33 [20-42] ppm v 22 [16-32] ppm, p < 0.01;
      carboxyhemoglobin 1.3% [1.0%-1.3%] v 0.9% [0.6%-1.0%], p < 0.01). To exclude that
      the observed increases were caused by CO accumulation during CPB, the authors
      also assessed carboxyhemoglobin concentrations in the arterial and venous limb of
      the oxygenator, indicating that CO is eliminated across the membrane oxygenator
      during CPB. CONCLUSIONS: Cardiac surgery with cardiopulmonary bypass is
      associated with an increase in endogenous CO production.

PMID- 19394870
TI  - In response to "A modified 'over-the-needle' technique for arterial cannulation".

PMID- 19394871
TI  - The right sided great vessels by cardiac multidetector computed tomography:
      normative reference values among healthy adults free of cardiopulmonary disease,
      hypertension, and obesity.
AB  - RATIONALE AND OBJECTIVES: We sought to derive normative reference values for the
      thoracic great vessels using multidetector computed tomography (MDCT) in a
      healthy normotensive non-obese population free of cardiovascular disease.
      MATERIALS AND METHODS: Non-gated axial computed tomography (CT) of the chest has
      traditionally been used to evaluate normal great vessel anatomy for prognosis and
      management. However, non-gated axial chest CT cannot account for the obliquity,
      systolic expansion, and non-axial motion of the great vessels during the cardiac
      cycle and may misclassify patients as normal or abnormal for prognostic and
      management purposes. To date, normative reference values for double-oblique,
      short-axis great vessel diameters have not been established using current
      generation electrocardiogram (ECG)-gated 64-detector row MDCT. A total of 103
      (43% women, age 51 +/- 14 years) consecutive normotensive, non-obese adults free
      of cardiopulmonary or great vessel structural disease, arrhythmias, or
      significant coronary artery disease were studied by MDCT. Individuals underwent
      examination for determination of end-diastolic (ED) pulmonary artery (PA) and
      superior vena cava (SVC) dimensions in double-oblique short axes for comparison
      with the ascending aorta and the right-sided cardiac chambers. RESULTS: For right
      sided great vessels, the 5th to 95th interval was 1.89-3.03 cm for ED PA diameter
      and 1.08-4.42 cm(2) for SVC cross-sectional area. The pulmonary artery to
      ascending aortic (PA-to-Ao) ratio was 0.66-1.13. In multivariate analysis, the PA
      was significantly associated with weight, whereas the PA-to-Ao ratio was
      inversely associated with age. Axial PA measurements were significantly higher
      and PA-to-Ao measurements significantly lower than corresponding short axis
      measurements (P = .04 and P < .001, respectively). CONCLUSIONS: This study
      establishes ECG-gated MDCT reference values for right-sided great vessel
      dimensions derived from a healthy population of individuals free of
      cardiovascular disease, hypertension, and obesity. The traditional axial PA-to-Ao
      discriminant value of 1 for pulmonary hypertension is a poor diagnostic tool
      because it encompasses normal patients and is negatively affected by age.
      Thoracic great vessels should be measured by CT in ECG-gated double-oblique short
      axis for accurate quantitation. These data may serve as a reference to identify
      right-sided great vessel pathology in individuals being referred for ECG-gated
      MDCT imaging.

PMID- 19394872
TI  - Diffusion weighted imaging of pediatric and adolescent malignancies with regard
      to detection and delineation: initial experience.
AB  - RATIONALE AND OBJECTIVE: To assess the value of diffusion weighted imaging (DWI)
      magnetic resonance imaging (MRI) in pediatric and adolescent tumor patients with
      focus on detection and delineation of malignant tumors of the central nervous
      system, chest, abdomen, and musculoskeletal system. MATERIALS AND METHODS: Twenty
      nine pediatric and adolescent patients (17 males, 12 females, age, 2 months-20
      years, mean age: 8.9 years) with clinically suspected malignant tumors were
      examined with use of a 1.5-T MR scanner with open bore design without sedation or
      general anesthesia. DWI images were acquired with a single-shot echo planar
      imaging (EPI) sequence in free breathing with b-values of 0, 500, and 1000
      mm/s(2). Images were assessed by two readers in consensus. Artifacts in DWI were
      graded as not relevant, acceptable, or nondiagnostic. DWI/apparent diffusion
      coefficient maps were correlated with T1-weighted post-contrast images, and the
      detectability and correct delineation of the tumors were graded using a three
      grade scale. RESULTS: Free-breathing DWI was successfully performed in all
      patients. In 27 patients, no relevant artifacts were observed; acceptable
      artifacts were seen in two patients. In all patients, malignancies were detected
      both on DWI and T1-weighted gadolinium images. Detection and delineation of
      tumors were possible in all cases with both sequences; T1-weighted gadolinium
      imaging was superior to DWI in only three patients. Additionally, small diffusion
      restricted lymph nodes were detected in three patients. CONCLUSION: DWI is
      reliable for the accurate detection and delineation of malignant pediatric and
      adolescent tumors.

PMID- 19394873
TI  - Commercially available computer-aided detection system for pulmonary nodules on
      thin-section images using 64 detectors-row CT: preliminary study of 48 cases.
AB  - RATIONALE AND OBJECTIVES: Most studies of computer-aided detection (CAD) for
      pulmonary nodules have focused on solid nodule detection. The aim of this study
      was to evaluate the performance of a commercially available CAD system in the
      detection of pulmonary nodules with or without ground-glass opacity (GGO) using
      64-detector-row computed tomography compared to visual interpretation. MATERIALS
      AND METHODS: Computed tomographic examinations were performed on 48 patients with
      existing or suspicious pulmonary nodules on chest radiography. Three radiologists
      independently reported the location and pattern (GGO, solid, or part solid) of
      each nodule candidate on computed tomographic scans, assigned each a confidence
      score, and then analyzed all scans using the CAD system. A reference standard was
      established by a consensus panel of different radiologists, who found 229
      noncalcified nodules with diameters > or = 4 mm. True-positive and false-positive
      results and confidence levels were used to generate jackknife alternative free
      response receiver-operating characteristic plots. RESULTS: The sensitivity of GGO
      for 3 radiologists (60%-80%) was significantly higher than that for the CAD
      system (21%) (McNemar's test, P < .0001). For overall and solid nodules, the
      figure-of-merit values without and with the CAD system were significantly
      different (P = .005-.04) on jackknife alternative free-response receiver
      operating characteristic analysis. For GGO and part-solid nodules, the figure-of
      merit values with the CAD system were greater than those without the CAD system,
      indicating no significant differences. CONCLUSION: Radiologists are significantly
      superior to this CAD system in the detection of GGO, but the CAD system can still
      play a complementary role in detecting nodules with or without GGO.

PMID- 19394874
TI  - Comparative evaluation of the geometrical accuracy of intravascular magnetic
      resonance imaging: a phantom study.
AB  - RATIONALE AND OBJECTIVES: To evaluate and compare the accuracy of cross-sectional
      imaging using an intravascular antenna in the context of vascular morphological
      measurements performed during a magnetic resonance imaging (MRI)-guided vascular
      intervention. MATERIALS AND METHODS: Cross-sectional imaging of a multimodality
      vascular phantom was performed using intravascular and surface MRI, multidetector
      computed tomography, and intravascular ultrasound (IVUS). Using a balanced steady
      state free-precession sequence, 18 sequences parameters sets were investigated
      (12 for intravascular MRI and 6 for surface MRI). Vessel diameters for all images
      and modalities were computed using an automated vessel segmentation algorithm.
      RESULTS: Using IVUS as a gold standard, imaging using an intravascular antenna
      leads to an increase in geometrical accuracy in comparison to traditional surface
      MRI. This level of accuracy appears to follow a significant inverse
      proportionality relation in respect to vessel wall signal-to-noise ratio (SNR).
      Taking into account the rapid decrease in SNR as a function of the distance to
      the intravascular antenna, these results imply that, for a given level of
      geometrical accuracy, faster sequences can be used for the imaging of smaller
      vessels. CONCLUSION: Imaging using an intravascular antenna appears as a valuable
      assistance to increase the accuracy of vascular morphological measurements. This
      increase in geometrical accuracy would be beneficial during the realization of an
      MRI-guided intervention, either to perform pretreatment measurements or to assess
      the outcome of the procedure. Acquisition parameters should be tailored to vessel
      size and procedural time constraints.

PMID- 19394875
TI  - Pediatric MDCT: towards assessing the diagnostic influence of dose reduction on
      the detection of small lung nodules.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the effect of
      reduced tube current (dose) on lung nodule detection in pediatric multidetector
      array computed tomography (MDCT). MATERIALS AND METHODS: The study included
      normal clinical chest MDCT images of 13 patients (aged 1-7 years) scanned at tube
      currents of 70 to 180 mA. Calibrated noise addition software was used to simulate
      cases as they would have been acquired at 70 mA (the lowest original tube
      current), 35 mA (50% reduction), and 17.5 mA (75% reduction). Using a validated
      nodule simulation technique, small lung nodules of 3 to 5 mm in diameter were
      inserted into the cases, which were then randomized and rated independently by
      three experienced pediatric radiologists for nodule presence on a continuous
      scale ranging from zero (definitely absent) to 100 (definitely present). The
      observer data were analyzed to assess the influence of dose on detection accuracy
      using the Dorfman-Berbaum-Mets method for multiobserver, multitreatment receiver
      operating characteristic (ROC) analysis and the Williams trend test. RESULTS: The
      areas under the ROC curves were 0.95, 0.91, and 0.92 at 70, 35, and 17.5 mA,
      respectively, with standard errors of 0.02 and interobserver variability of 0.02.
      The Dorfman-Berbaum-Mets method and the Williams trend test yielded P values for
      the effect of dose of .09 and .05, respectively. CONCLUSION: Tube current (dose)
      has a weak effect on the detection accuracy of small lung nodules in pediatric
      MDCT. The effect on detection accuracy of a 75% dose reduction was comparable to
      interobserver variability, suggesting a potential for dose reduction.

PMID- 19394876
TI  - Improved detection of hepatic metastases with contrast-enhanced low mechanical
      index pulse inversion ultrasonography during the liver-specific phase of
      sonazoid: observer performance study with JAFROC analysis.
AB  - RATIONALE AND OBJECTIVES: To compare B-mode ultrasonography (US) alone with the
      combination of B-mode and contrast-enhanced (Sonazoid) late-phase pulse-inversion
      US for the detection of hepatic metastases by use of jackknife free-response
      receiver-operating characteristic (JAFROC) analysis. MATERIALS AND METHODS:
      Twenty-seven patients with 57 hepatic metastases and 6 patients without hepatic
      metastases underwent B-mode and contrast-enhanced US. We used the diagnoses
      established by contrast-enhanced computed tomography and contrast-enhanced US as
      the standard of reference. All ultrasonographic scanning was performed by an
      experienced radiologist with a routine clinical procedure. All scanning data were
      archived with digital cine clips. A review system, which can display pairs of
      cine clips for B-mode and contrast-enhanced US side by side, was developed for
      off-site observer study. Seven radiologists interpreted each case individually
      first by B-mode US only, and then by the combination with contrast-enhanced US by
      identifying locations of possible candidates for hepatic metastasis with their
      confidence ratings. The figure-of-merit (FOM) values, sensitivity, and false
      positives per case were estimated for B-mode US alone, and for the combination of
      B-mode and contrast-enhanced US. RESULTS: The sensitivities of the combined
      ultrasonographic imaging (mean, 72.2%) were clearly improved from that of B-mode
      US alone (mean, 41.6%) while reducing the average number of false positives from
      1.1 to 0.5 per case. In the jackknife analysis, there was a statistically
      significant difference between mean FOM values for the combined imaging (0.76)
      and for B-mode US alone (0.44, P < .00001). CONCLUSION: Evaluating cine clips of
      contrast-enhanced liver US together with B-mode US could improve physicians'
      accuracy for detection of hepatic metastases.

PMID- 19394877
TI  - Determinants of micro-embolic signals in patients with atherosclerotic plaques of
      the internal carotid artery.
AB  - BACKGROUND AND PURPOSE: This study aimed to investigate the embolic potential of
      carotid plaques, employing both the presence and the rate of micro-embolic
      signals (MESs), based on the presence and timing (current or past) of symptoms,
      degree of stenosis and ultrasonic characteristics of plaques. METHODS: We used
      the transcranial Doppler (TCD) to monitor MES and the Doppler ultrasound to
      classify carotid plaques in newly symptomatic (acute stroke or transient
      ischaemic attack (TIA)), formerly symptomatic (relevant stroke or TIA per
      anamnesis) and asymptomatic patients with internal carotid artery (ICA) stenosis.
      RESULTS: Stroke-related arteries evidenced a significantly greater presence of
      MES than the TIA-related and asymptomatic arteries (p=0.04), with no significant
      difference found between the latter two groups (stroke: 42/90, 46.7%; TIA: 15/49,
      30.6%; asymptomatic: 40/130, 30.8%). Adjustment for anti-platelet treatment did
      not change this finding. The degree of stenosis, ultrasonic characteristics of
      texture and the density of plaques were not found to be associated with the
      presence or quantity of MES. CONCLUSION: MESs are present significantly more
      often in stenosed, stroke-related carotid arteries as compared with TIA-related
      or asymptomatic arteries. Neither the ultrasonic characteristics nor the degree
      of stenosis were found to influence the presence or rate of MES.

PMID- 19394878
TI  - Effects of a stretching regime on stride length and range of motion in equine
      trot.
AB  - The aim of this study was to quantify the effects of two different 8-week
      stretching regimes on stride length (SL) and range of motion (ROM) in the equine
      trot. Eighteen horses were divided into three matched groups: a 6 days/week
      stretching regime (6DSR), a 3 days/week stretching regime (3DSR) and a control no
      stretching regime (NSR). SL and ROM data were collected at weeks 0, 2, 4, 6 and 8
      for trot in-hand. Stretching had no significant effect on SL. A number of
      significant differences were found in joint ROM between treatments in the
      shoulder, stifle and hock, suggesting some negative biomechanical effects of the
      6DSR. Stretching daily may be too intensive and cause delayed onset of muscle
      soreness. Further examination of stretch frequency may establish its potential to
      enhance performance and welfare.

PMID- 19394879
TI  - Investigating horse-human interactions: the effect of a nervous human.
AB  - The heart rates (HR) of horses and the people leading them (10 horses, 20
      people), and riding them (17 horses, 17 people), were recorded in an indoor
      arena. The horses were Swedish leisure horses of mixed ages, sex and breed. All
      except two of the people were female and all were of mixed age and riding
      experience. Each horse-human pair walked or rode between points A and B (30m)
      four times on each test occasion. However, just before the fourth pass,
      participants were told that an umbrella would be opened as they rode, or led, the
      horse past the assistant. The umbrella was not opened, so this pass was no
      different to the previous control occasions, but nevertheless there was an
      increase in HR for both the person (leading, P=0.06; riding, P<0.05) and the
      horse (being led, P<0.05; being ridden, P<0.05). The findings indicate that
      analysis of HR recorded simultaneously from people and horses under different
      experimental handling or riding conditions presents a useful tool to investigate
      horse-human interactions.

PMID- 19394880
TI  - How equitation science can elucidate and refine horsemanship techniques.
AB  - The long-held belief that human dominance and equine submission are key to
      successful training and that the horse must be taught to 'respect' the trainer
      infers that force is often used during training. Many horses respond by trialling
      unwelcome evasions, resistances and flight responses, which readily become
      established. When unable to cope with problem behaviours, some handlers in the
      past might have been encouraged to use harsh methods or devices while others may
      have called in a so-called 'good horseman' or 'horse whisperer' to remediate the
      horse. Frequently, the approaches such practitioners offer could not be applied
      by the horse's owner or trainer because of their lack of understanding or
      inability to apply the techniques. Often it seemed that these 'horse-people' had
      magical ways with horses (e.g., they only had to whisper to them) that achieved
      impressive results although they had little motivation to divulge their
      techniques. As we begin to appreciate how to communicate with horses sensitively
      and consistently, misunderstandings and misinterpretations by horse and trainer
      should become less common. Recent studies have begun to reveal what comprises the
      simplest, most humane and most effective mechanisms in horse training and these
      advances are being matched by greater sharing of knowledge among practitioners.
      Indeed, various practitioners of what is referred to here as 'natural
      horsemanship' now use techniques similar to the 'whisperers' of old, but they are
      more open about their methods. Reputable horse trainers using natural
      horsemanship approaches are talented observers of horse behaviour and respond
      consistently and swiftly to the horse's subtle cues during training. For example,
      in the roundpen these trainers apply an aversive stimulus to prompt a flight
      response and then, when the horse slows down, moves toward them, or offers space
      reducing affiliative signals, the trainer immediately modifies his/her agonistic
      signals, thus negatively reinforcing the desired response. Learning theory and
      equine ethology, the fundamentals of the emerging discipline of equitation
      science, can be used to explain almost all the behaviour modification that goes
      on in these contexts and in conventional horsemanship. By measuring and
      evaluating what works and what does not, equitation science has the potential to
      have a unifying effect on traditional practices and developing branches of
      equitation.

PMID- 19394881
TI  - Evidence of feline herpesvirus-1 DNA in the vestibular ganglion of domestic cats.
AB  - In humans, herpes simplex virus type-1 has recently been detected in the
      vestibular ganglion (VG) and labyrinth (VL) and may be associated with vestibular
      signs. Feline herpesvirus-1 (FHV-1) is widespread amongst cat populations and
      affects many different tissues. The aim of this pilot study was to investigate
      the presence of FHV-1 DNA in the VG and VL of randomly selected domestic cats
      using PCR. FHV-1 DNA was detected in the VG of 14% of the cats. There was no
      detectable FHV-1 DNA in the VL of any cat. None of the infected cats had
      vestibular signs related to the VG infection.

PMID- 19394882
TI  - Chronic pain in women after breast augmentation: prevalence, predictive factors
      and quality of life.

PMID- 19394883
TI  - Water molecule contributions to proton spin-lattice relaxation in rotationally
      immobilized proteins.
AB  - Spin-lattice relaxation rates of protein and water protons in dry and hydrated
      immobilized bovine serum albumin were measured in the range of (1)H Larmor
      frequency from 10 kHz to 30 MHz at temperatures from 154 to 302 K. The water
      proton spin-lattice relaxation reports on that of protein protons, which causes
      the characteristic power law dependence on the magnetic field strength. Isotope
      substitution of deuterium for hydrogen in water and studies at different
      temperatures expose three classes of water molecule dynamics that contribute to
      the spin-lattice relaxation dispersion profile. At 185 K, a water (1)H relaxation
      contribution derives from reorientation of protein-bound molecules that are
      dynamically uncoupled from the protein backbone and is characterized by a
      Lorentzian function. Bound-water-molecule motions that can be dynamically
      uncoupled or coupled to the protein fluctuations make dominant contributions at
      higher temperatures as well. Surface water translational diffusion that is
      magnetically two-dimensional makes relaxation contributions at frequencies above
      10 MHz. It is shown using isotope substitution that the exponent of the power law
      of the water signal in hydrated immobilized protein systems is the same as that
      for protons in lyophilized proteins over four orders of magnitude in the Larmor
      frequency, which implies that changes in the protein structure associated with
      hydration do not affect the (1)H spin relaxation.

PMID- 19394884
TI  - [Prevalence of modifiable risk factors in the nursing diagnosis of risk for
      sudden infant death syndrome].
AB  - OBJECTIVE: To measure the prevalence of modifiable risk factors for the nursing
      diagnosis of risk of sudden infant death syndrome (RSIDS), and to establish the
      association between the prevalence found and the sociodemographic characteristics
      of the sample. MATERIAL AND METHODS: The sample was composed of 384 mothers
      (Spaniards, Moroccans and Ecuadorians). Data were collected in the maternity ward
      of Sta. M del Rosell Hospital in Cartagena (Murcia) from June to November 2007
      through a questionnaire containing items on sociodemographic variables and
      questions about upbringing habits and practices, which are defined as modifiable
      risk factors by the NANDA-I taxonomy. In the statistical analysis, the Chi-square
      test was used for qualitative variables and Student's t-test and analysis of
      variance were used for quantitative variables. RESULTS: A total of 77.1% of
      newborns were diagnosed with RSIDS related to modifiable risk factors. Notable
      was the high prevalence of risk factors such as the choice of side-lying position
      to put the newborn to bed in 39.8% (153) and smoking during pregnancy in 25.7%
      (99). Statistically significant associations were found (p<0.001) between the
      diagnosis of RSIDS and the mother's nationality, educational level and household
      income. CONCLUSION: The high prevalence of some modifiable risk factors among
      newborns raises the need to provide more information about upbringing habits and
      practices for SIDS prevention, not only in Infant Nursing Consulting Rooms but
      also throughout pregnancy and in the first days of life of the newborn.

PMID- 19394885
TI  - [Anatomic bases of the infrahyoid flap: vascular pedicles and innervation].
AB  - The infrahyoid flap is used in head and neck reconstruction, especially in oral
      defect. This study is designed to determine vascular pedicles and innervation of
      the infrahyoid muscles and flap. MATERIALS AND METHOD: The neck regions of 12
      injected cadavers were investigated bilaterally. RESULTS: The arterial pedicles
      of the infrahyoid muscles are the superior and inferior thyroid arteries. The
      arterial pedicles of the flap are the superior thyroid artery. The venous
      pedicles of the muscles and flap are the superior thyroid, lingual and facial
      veins. The infrahyoid flap is innervated by the ansa cervicalis. CONCLUSION: The
      infrahyoid flap seems to be an excellent flap for oral, oropharynx and superior
      facial part reconstruction. It can be harvested easily in the same operation
      area.

PMID- 19394886
TI  - [Tamoxifen in the adjuvant setting for breast cancer: Reflexions about the risk
      of uterine carcinosarcoma].
AB  - A descriptive analysis of available data on reported cases of uterine
      carcinosarcomas associated with tamoxifen therapy is undertaken. The role of
      aromatase inhibitors as alternative to tamoxifen therapy in the adjuvant setting
      of breast cancer is discussed. The eventual implications of the presumed
      association of uterine carcinosarcoma and tamoxifen therapy on the choice of the
      therapeutic agent in the adjuvant setting of hormone-sensitive breast cancer are
      discussed.

PMID- 19394887
TI  - [Delivery of twins].
AB  - The assessment of optimal delivery for twin gestations is complex due to the
      relatively high frequency of obstetrical complications and to the heterogeneity
      of delivery management in these conditions. The extern validity of the Anglo
      Saxon studies is limited in particular because delivery management of the second
      twin (approach of external cephalic version) differs from the French one
      (approach of internal version and/or total breech extraction) in cases of non
      vertex second twin. Anglo-Saxon studies suggest that a planned vaginal delivery
      is associated to an increased risk of neonatal morbidity for second twin compared
      to first twin at term, in particular in cases of combined vaginal-cesarean birth.
      To reduce the interval twin-to-twin delivery interval and the number of combined
      vaginal-cesarean births, in our opinion, one must stop to perform external
      cephalic version and recommend a routinely active management for the second non
      vertex twin delivery. With this active management, there is no evidence to
      support planned cesarean section for twins. Nevertheless, active management
      requires training as internal version might be difficult to perform, and
      therefore it is essential to pursue to teach junior obstetrician these obstetric
      maneuvers. There is limited role for trial of labor after cesarean delivery in
      twin gestation with a policy of active management.

PMID- 19394888
TI  - [Dead children born: Current regulation, inscription to registry office differs].
AB  - From a juridical point of view, in France, we become a "person" only when we are
      born "living" and "viable". These two criteria are necessary, but the threshold
      of viability is not defined by the law. The general education of registry office
      leaned on a circular fixing a << threshold of viability >> itself based on a
      recommendation of the Worldwide Organization of Health (WHO). The fetus was
      considered as viable after a term of twenty-two weeks of amenorrhea or if it had
      a weight over or equal to 500 grammes. The inscription to Registry office
      differs, as well as the taking care of the body of the child, depending on
      whether he was born living, viable and living and not viable, dead and viable, or
      dead and not viable. In France, the civil officer established an act of child
      declared lifeless when the child was born living but not viable or when the child
      is death - born but viable. However, parents of not viable and born dead
      children, often close to the threshold of viability, also liked to acquire an act
      of lifeless child, to be able to organize funeral has child lifeless and to
      inscribe it in their family record book. The act of child declared lifeless
      allows to inscribe the child on the family record book if the parents wish and
      give to the families the delay of ten days to claim the body. By judgment of
      February 6th, 2008, the Supreme Court of appeal cancelled rulings where the
      threshold had been kept to refuse the deliverance of an act of lifeless child.
      Her Supreme court of appeal considers that law does not impose de threshold from
      which the recognition of the status of lifeless child would be possible. Since
      the decrees of August, 2008, there is no border anymore of minimum of term or
      weight. Consequently, the lifeless born children after an unprompted delivery or
      a medical break, the pregnancy can be inscribed on the civil record. On the other
      hand, it is not possible for the precocious wrong coat and the termination of
      pregnancy.

PMID- 19394889
TI  - One-pot three-component Mannich-type reactions using sulfamic acid catalyst under
      ultrasound irradiation.
AB  - Sulfamic acid (NH(2)SO(3)H, SA) was used as an efficient, inexpensive, non-toxic
      and recyclable green catalyst for the ultrasound-assisted one-pot Mannich
      reaction of aldehydes with ketones and amines. This ultrasound protocol has
      advantages of high yield, mild condition, no environmental pollution, and simple
      work-up procedures. Most importantly, beta-aminocarbonyl compounds with ortho
      substituted aromatic amines are obtained in acceptable to good yields by this
      methodology for the first time.

PMID- 19394890
TI  - Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic
      therapies.
AB  - Angiogenesis, a key process for the growth of human cancers, has recently been
      exploited for the development of a novel class of cancer therapeutics that was
      thought to have wide applications and not to induce resistance in the clinical
      setting. Indeed, anti-angiogenic therapy has become an important option for the
      management of several human malignancies. However, a significant number of
      patients either do not respond to anti-angiogenic agents or fairly rapidly
      develop resistance. In addition, the benefit of anti-angiogenic therapy is
      relatively short-lived and the majority of patients eventually relapses and
      progresses. Several mechanisms of resistance to anti-angiogenic therapy have been
      recently proposed. The current review focuses on the role of intra-tumor hypoxia
      as a mechanism of resistance to anti-angiogenic agents and speculates on
      therapeutic approaches that might circumvent resistance and thereby improve
      clinical outcome.

PMID- 19394891
TI  - STANDing strong, resistance proteins instigators of plant defence.
AB  - Resistance (R) proteins are involved in specific pathogen recognition and
      subsequent initiation of host defence. Most R proteins are nucleotide binding -
      leucine rich repeat (NB-LRR) proteins, which form a subgroup within the STAND
      (signal transduction ATPases with numerous domains) family. Activity of these
      multi-domain proteins depends on their ability to bind and hydrolyse nucleotides.
      Since R protein activation often triggers cell-death tight regulation of
      activation is essential. Autoinhibition, which seems to be accomplished by
      intramolecular interactions between the various domains, is important to retain R
      proteins inactive. This review summarizes recent data on intra- and
      intermolecular interactions that support a model in which pathogen perception
      triggers a series of conformational changes, allowing the newly exposed NB domain
      to interact with downstream signalling partners and activate defence signalling.

PMID- 19394892
TI  - Detection of changes of high-frequency activity by statistical time-frequency
      analysis in epileptic spikes.
AB  - OBJECTIVE: A novel type of statistical time-frequency analysis was developed to
      elucidate changes of high-frequency EEG activity associated with epileptic
      spikes. METHODS: The method uses the Gabor Transform and detects changes of power
      in comparison to background activity using t-statistics that are controlled by
      the false discovery rate (FDR) to correct type I error of multiple testing. The
      analysis was applied to EEGs recorded at 2000 Hz from three patients with mesial
      temporal lobe epilepsy. RESULTS: Spike-related increase of high-frequency
      oscillations (HFOs) was clearly shown in the FDR-controlled t-spectra: it was
      most dramatic in spikes recorded from the hippocampus when the hippocampus was
      the seizure onset zone (SOZ). Depression of fast activity was observed
      immediately after the spikes, especially consistently in the discharges from the
      hippocampal SOZ. It corresponded to the slow wave part in case of spike-and-slow
      wave complexes, but it was noted even in spikes without apparent slow waves. In
      one patient, a gradual increase of power above 200 Hz preceded spikes.
      CONCLUSIONS: FDR-controlled t-spectra clearly detected the spike-related changes
      of HFOs that were unclear in standard power spectra. SIGNIFICANCE: We developed a
      promising tool to study the HFOs that may be closely linked to the
      pathophysiology of epileptogenesis.

PMID- 19394893
TI  - 3D source localization derived from subdural strip and grid electrodes: a
      simulation study.
AB  - OBJECTIVE: Little experience exists in the application of source reconstruction
      methods to recordings from subdural strip and grid electrodes. This study
      addressed the question, whether reliable and accurate 3D source localization is
      possible from the Electrocorticogram (ECoG). METHODS: The accuracy of source
      reconstruction was investigated by simulations and a case study. Simulated
      sources were used to compute potentials at the electrode positions derived from
      the MRI of a patient with subdural electrodes. Used procedures were the linear
      estimation (minimum norm) algorithm and the MUSIC (MUltiple SIgnal
      Classification) scan. RESULTS: Maxima of linear estimation were attracted to
      adjacent electrodes. Reliable localization with a localization error 15 mm was
      only achieved for about 35% of the original source positions. Maxima of the MUSIC
      metric were identical to original positions for simulations without noise. Noise
      reduced the percentage of reliable solutions down to a 79.0%. Electrode contacts
      distant to the source had small influence on localization accuracy. The case
      study supported simulation results. CONCLUSION: Reliable source reconstruction
      derived from ECoG can be achieved by the application of the MUSIC algorithm.
      Linear estimation needs additional compensation mechanisms. SIGNIFICANCE: MUSIC
      based 3D localization based on ECoG has the potential improving epilepsy
      diagnosis and cognitive research.

PMID- 19394894
TI  - Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory
      inflammatory breast cancer: final results and survival of the expanded HER2+
      cohort in EGF103009, a phase II study.
AB  - BACKGROUND: Inflammatory breast cancer is an aggressive and biologically distinct
      form with a higher frequency of HER2 overexpression than other breast cancers.
      For patients with resistance to conventional anthracycline or taxane and
      trastuzumab treatment, options are limited. Lapatinib, an oral reversible
      inhibitor of epidermal growth factor receptor tyrosine kinases, previously had a
      50% response rate in a cohort of 30 patients with HER2-overexpressing (HER2+)
      recurrent or anthracycline-refractory inflammatory breast cancer. We aimed to
      assess efficacy of lapatinib in an expanded cohort of patients with relapsed or
      refractory HER2+ disease. METHODS: From March, 2005, to September, 2007, 126
      patients with relapsed or refractory HER2+ inflammatory breast cancer were
      treated with lapatinib 1500 mg once daily in a non-randomised, open-label, phase
      II study. Pretreatment tumour biopsies were done to verify pathological features
      of inflammatory breast cancer. Skin disease was assessed every 4 weeks, and
      response in sites of measurable locally advanced or metastatic disease were
      assessed by response evaluation in solid tumours (RECIST) criteria every 8 weeks.
      The primary aim was to assess combined objective response rate, by clinically
      evaluable skin disease criteria and RECIST, if applicable. Analyses were done by
      intention to treat; patients with missing data were treated as non-responders.
      This study is registered with ClinicalTrials.gov, number NCT00105950. FINDINGS:
      Clinical presentation and biomarker analysis showed a tumour molecular profile
      consistent with inflammatory breast cancer. No patients had complete response. 49
      patients (39%; 95% CI 30-48) had partial response. Median progression-free
      survival was 14.6 weeks (95% CI 12.1-16.0), with median duration of response of
      20.9 weeks (12.7-32.1). Likelihood of response to lapatinib was not affected by
      previous treatment with trastuzumab. 130 (92%) of 141 patients had at least one
      adverse event; 45 (32%) had serious adverse events, the most common were dyspnoea
      (eight patients) and pleural effusion (six). Five patients had fatal adverse
      events that were possibly treatment related. INTERPRETATION: Lapatinib
      monotherapy is a potentially effective treatment for relapsed or refractory HER2+
      inflammatory breast cancer. FUNDING: GlaxoSmithKline.

PMID- 19394895
TI  - Ins and outs of cardiac voltage-gated potassium channels.
AB  - Voltage-gated potassium (Kv) channels play an important role in regulating
      cardiac muscle excitability by controlling action potential duration and
      frequency. Essential for this activity is proper localization and organization of
      the cardiac Kv channels in specific microdomains of the plasma membrane. The
      underlying processes involve tight control of anterograde and retrograde Kv
      channel trafficking into and out of the plasma membrane. Thus, cardiac Kv channel
      density at the cell surface is regulated by a dynamic interplay of endocytotic
      and recycling pathways, the mechanisms of which are mostly unknown. Recent
      studies have indicated that the lipid composition in the Kv channel surround
      profoundly influences these processes. Local differences in lipid composition
      altering the mechanic state of the lipid bilayer or a specific interaction with
      an important domain of the Kv channel markedly affect voltage-sensitive gating,
      clustering, and mobility of cardiac Kv channels and, thereby, the excitability in
      the healthy and diseased heart muscles.

PMID- 19394896
TI  - Nursing patients with acute chest pain: practice guided by the Prince Edward
      Island conceptual model for nursing.
AB  - Current research suggests that pain is a relatively common phenomenon with 60-90%
      of patients presenting to emergency departments reporting pain (e.g., chest pain,
      trauma, extremity fractures and migraine headache) that require treatment [Hogan,
      S.L., 2005. Patient satisfaction with pain management in the emergency
      department. Advanced Emergency Nursing Journal 27(4), 284-294]. This article
      explores the use of conceptual theoretical empirical (C-T-E) framework to guide a
      senior nursing student in a case study of patient with chest pain. The Middle
      Range Theory of Pain described by Good [Good, M., 1998. A middle-range theory of
      acute pain management: use in research. Nursing Outlook 46(3), 120-124] and
      Melzack's [Melzack, R., 1987. The short-form McGill pain questionnaire. Pain, 30,
      191-197] short form McGill pain questionnaire were applied along with the Prince
      Edward Island conceptual model (PEICM) for nursing. Results indicate that the
      nursing student increased her ability to work in partnership, assess relevant and
      specific information, and identify a number of strategies to help the patient
      achieve pain control by using a complement of pharmacological and non
      pharmacological interventions. Moreover, the C-T-E approach provided an organized
      and systematic theoretical approach for the nursing student to assist a patient
      in pain control.

PMID- 19394897
TI  - Female hypospadias with vaginal stones: a rare congenital anomaly.
AB  - OBJECTIVE: To highlight the unusual and late presentation of the rare congenital
      urethral anomaly of female hypospadias and its management. PATIENTS AND METHODS:
      We report on four cases (aged 18-65 years; mean 34 years and 3 months) of female
      hypospadias; two presented with urinary incontinence, recurrent UTI since birth
      and dyspareunia, and two were diagnosed during catheterization following
      retention of urine. One of the younger patients had vaginal stones. We reached
      the diagnosis by catheterization, voiding cysto-urethrogram and panendoscopy. A
      periurethral vaginal flap urethroplasty was performed in three layers with
      excellent results in three cases, and one patient was managed conservatively.
      RESULTS: Results were excellent in the three cases treated surgically. Patients
      were continent after urethroplasty and were happy to pass urine in a stream with
      complete emptying of the bladder for the first time in their life. Two of them
      had fertility problems due to urogenital septal defects and are undergoing
      appropriate treatment. CONCLUSIONS: Vaginal voiding leads to urinary stagnation
      in the vagina causing urinary pseudo-incontinence and vaginal stones. Early
      diagnosis requires a high index of suspicion.

PMID- 19394898
TI  - Spinal extradural arachnoid cyst.
AB  - BACKGROUND CONTEXT: Spinal extradural arachnoid cysts are uncommon expanding
      lesions. Idiopathic arachnoid cysts are not associated with trauma or other
      inflammatory insults. If they enlarge, they usually present with progressive
      signs and symptoms of neural compression. PURPOSE: Total removal of the cyst and
      repair of the dural defect is the primary treatment for large thoracolumbar
      spinal extradural arachnoid cysts causing neurogenic claudication. Laminoplasty
      may prevent spinal deformities in long segmental involvement. STUDY DESIGN: A
      clinical case was performed. PATIENT SAMPLE: We report a case of 25-year-old man
      with 1-year history of progressive back pain radiating to both legs. His
      diagnosis was dorsal intraspinal extradural cystic lesion longing from the level
      of T11 to L2 on magnetic resonance imaging. OUTCOME MEASURES: The patient's pain
      levels were noted as he reported. Physiologic outcome was assessed on pre- and
      postoperative motor and sensory examination. METHODS: The patient underwent a T11
      L2 laminotomy and radical cyst wall resection was performed. A small
      communication with the subarachnoid space was seen at the level of T12. It was
      sealed with tissue fibrinogen after repair with primary suture. Titanium
      miniplates were used for laminoplasty. RESULTS: Follow-up magnetic resonance
      imaging demonstrated cyst resolution, and neurologic examination revealed no
      sensory and motor deficit. CONCLUSION: Extradural arachnoid cysts are primarily
      treated with total removal of the cyst wall and closure of the dural defect.
      Surgical treatment is curative for this rare lesion.

PMID- 19394899
TI  - Electrochemistry of myoglobin in Nafion and multi-walled carbon nanotubes
      modified carbon ionic liquid electrode.
AB  - The direct electrochemistry of myoglobin (Mb) entrapped in the Nafion film on a
      multi-walled carbon nanotubes (MWCNTs) modified carbon ionic liquid electrode
      (CILE) had been investigated in this paper. By using a hydrophilic ionic liquid
      of 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIMBF(4)) as the modifier, a
      high-performance basal electrode was fabricated and further modified by MWCNTs,
      Mb and Nafion by a step-by-step casting method. Spectroscopic results indicated
      that the Mb molecule on the surface of MWCNTs/CILE retained its native structure.
      Cyclic voltammetric results showed that a pair of well-defined quasi-reversible
      redox peaks appeared in the pH 7.0 phosphate buffer solution (PBS), which was
      attributed to the direct electron transfer of Mb heme Fe(III)/Fe(II) redox
      couples with the modified electrode. The Nafion/Mb/MWCNTs/CILE gave excellent
      electrocatalytic activity towards different substrates including trichloroacetic
      acid (TCA), hydrogen peroxide (H(2)O(2)) and sodium nitrite (NaNO(2)).

PMID- 19394900
TI  - Real-time detection of cofactor availability in genetically modified living
      Saccharomyces cerevisiae cells--simultaneous probing of different geno- and
      phenotypes.
AB  - This work describes a mediated amperometric method for simultaneous real-time
      probing of the NAD(P)H availability in two different phenotypes, fermentative and
      respiratory, of the phosphoglucose isomerase deletion mutant strain of S.
      cerevisiae, EBY44 [ENY.WA-1A pgi1-1D::URA3], and its parental strain, ENY.WA-1A.
      The developed method is based on multichannel detection using microelectrode
      arrays. Its versatility was demonstrated by using four microelectrode arrays for
      simultaneously monitoring the NAD(P)H availability of both geno- and phenotypes
      under the influence of two different carbon sources, glucose and fructose, as
      well as the cytosolic and mitochondrial inhibitor and uncoupler, dicoumarol. The
      obtained results indicate that the method is capable of accurately and
      reproducibly (overall relative standard error of mean 3.2%) mapping the real-time
      responses of the cells with different genotype-phenotype combinations. The ENY.WA
      cells showed the same response to glucose and fructose when dicoumarol was used;
      fermentative cells indicated the presence of cytosolic inhibition and respiratory
      cells a net effect of mitochondrial uncoupling. EBY44 cells showed cytosolic
      inhibition with the exception of respiratory cells when fructose was used as
      carbon source.

PMID- 19394901
TI  - Label-free relative quantification method for low-abundance glycoproteins in
      human serum by micrOTOF-Q.
AB  - In this study, a label-free relative quantification strategy was developed for
      quantifying low-abundance glycoproteins in human serum. It included three steps:
      (1) immunodepletion of 12 high-abundance proteins, (2) enrichment of low
      abundance glycoproteins by multi-lectin column, (3) relative quantification of
      them between different samples by micrOTOF-Q. We also evaluated the specificity
      and efficiency of immunodepletion, the accuracy of protein quantification and the
      possible influence of immunodepletion, glycoprotein enrichment, trypsin digestion
      and peptide ionization on quantification. In conclusion, the relative
      quantification method can be effectively applied to the screening of low
      abundance biomarkers.

PMID- 19394902
TI  - Self-assembly of a swollen chitosan/chondroitin sulfate hydrogel by outward
      diffusion of the chondroitin sulfate chains.
AB  - A hydrogel constituted of chitosan (CT) and chondroitin sulfate (CS) was
      synthesized. In previously reported works the stochiometric ratio has been used,
      but in this paper an excess of CS (40% CT and 60% CS) was used because the
      hydrogel could be applied as a CS carrier. The hydrogel properties were
      investigated by differential scanning calorimetry, wide-angle X-ray scattering
      (WAXS), scanning electron microscopy, and high-performance liquid chromatography.
      Changes in the pH of the gel-surrounding liquid had a considerable effect on both
      the release and the molecular reorganization of CS. Furthermore, the formed
      hydrogel exhibited interesting parameters for use in biotechnology, such as water
      affinity, thermal properties and morphology upon sequential pH variation. The
      protonation or deprotonation of the different groups that participate in the
      complex formation and the coiling or uncoiling of like or unlike chains
      concomitant to the release of CS are believed to be the main factors affecting
      the hydrogel properties. CS was released mainly at pH higher than 6.5, the value
      of pK(aCT), and the released CS maximum fraction was approximately 0.5. The WAXS
      data demonstrated that the CT/CS complex in the hydrogel presented macromolecular
      reorganization at pHs ranging from 6 to 12.

PMID- 19394903
TI  - Gallium nitride induces neuronal differentiation markers in neural stem/precursor
      cells derived from rat cerebral cortex.
AB  - In the present study, gallium nitride (GaN) was used as a substrate to culture
      neural stem/precursor cells (NSPCs), isolated from embryonic rat cerebral cortex,
      to examine the effect of GaN on the behavior of NSPCs in the presence of basic
      fibroblast growth factor (bFGF) in serum-free medium. Morphological studies
      showed that neurospheres maintained their initial shape and formed many long and
      thick processes with the fasciculate feature on GaN. Immunocytochemical
      characterization showed that GaN could induce the differentiation of NSPCs into
      neurons and astrocytes. Compared to poly-d-lysine (PDL), the most common
      substrate used for culturing neurons, there was considerable expression of
      synapsin I for differentiated neurons on GaN, suggesting GaN could induce the
      differentiation of NSPCs towards the mature differentiated neurons. Western blot
      analysis showed that the suppression of glycogen synthase kinase-3beta (GSK
      3beta) activity was one of the effects of GaN-promoted NSPC differentiation into
      neurons. Finally, compared to PDL, GaN could significantly improve cell survival
      to reduce cell death after long-term culture. These results suggest that GaN
      potentially has a combination of electric characteristics suitable for developing
      neuron and/or NSPC chip systems.

PMID- 19394904
TI  - In vitro structural changes in porous HA/beta-TCP scaffolds in simulated body
      fluid.
AB  - Porous scaffolds of biphasic calcium phosphate (hydroxyapatite/beta-tricalcium
      phosphate (beta-TCP)) have been fabricated and changes induced both in phase
      composition and porous architecture by immersion in simulated body fluid (SBF)
      under static and orbital stirring conditions have been studied. The starting
      porous scaffolds exhibit a low and randomized micro- and mesoporosity, an
      interconnected macroporosity centered at 100 and 0.6microm, a fractal
      connectivity of D=2.981 and total percent porosity of ca. 80%. After immersion
      for up to 60days the micro- and mesoporosity increase slightly, which could be
      attributed to dissolution of the beta-TCP phase confirmed by transmission
      electron microscopy. The effects of the change in the porous framework with SBF
      immersion time favor the bioactive behavior of the tested materials, inducing a
      nucleation and growth of a nanocrystalline apatite phase as the interconnected
      macroporosity centered at 0.6microm is reduced. The macroporosity centered at
      100microm is still stable after 60days in SBF. Therefore, these biphasic calcium
      phosphate porous scaffolds combine bioactive behavior with the stability of
      interconnected macroporosity over large periods of soaking time in SBF under
      static and orbital stirring conditions.

PMID- 19394905
TI  - Influence of oxidation treatment on fatigue and fatigue-induced damage of
      commercially pure titanium.
AB  - In this investigation, the cyclic deformation behaviour of commercially pure
      titanium was characterized in axial stress controlled constant amplitude and load
      increase tests, as well as in rotating bending tests. The influence of different
      clinically relevant surface treatments (polishing, thermal and anodic oxidizing)
      on the fatigue behaviour was investigated. All tests were realized in oxygen
      saturated Ringer's solution. The cyclic deformation behaviour was characterized
      by mechanical hysteresis measurements. In addition, the change of the free
      corrosion potential and the corrosion current during the fatigue tests in
      simulated physiological media indicated such types of surface damage as slip
      bands, microcracks and oxide film ablation. Microstructural changes on the
      specimen surfaces were examined by scanning electron microscopy.

PMID- 19394906
TI  - Drug-eluting bioabsorbable stents - an in vitro study.
AB  - The aim of this study was to investigate the drug elution properties of novel
      drug-eluting bioabsorbable stents in vitro with four different drugs:
      dexamethasone, indomethacin, simvastatin and ciprofloxacin. Braided stents of
      poly-lactic acid (96l/4d) fibers were coated with a solution containing the
      appropriate bioabsorbable polymer and drug, with acetone as the solvent. Two
      different drug concentrations for both non-sterile and gamma sterilized stents
      were used for dexamethasone and indomethacin. For ciprofloxacin and simvastatin,
      only one drug dose was used. The stents were placed in sodium-phosphate-buffered
      saline in a shaking incubator (pH 7.4, +37 degrees C) and the eluted drug was
      measured periodically using an ultraviolet spectrometer. The drugs were
      hydrophobic to different degrees, as demonstrated by their various speeds of
      elution. In general, the higher the drug load in the stent, the faster the drug
      elution and the more hydrophilic the elution profile. In the cases of
      dexamethasone, indomethacin and ciprofloxacin, the sterilization decreased the
      drug elution rate slightly and the elution started earlier. However, in the case
      of ciprofloxacin, the gamma sterilization increased the drug elution rate
      slightly. Sustained elution was achieved for all four drugs. It was also evident
      that both the concentration and the hydrophility of the drug had a great
      influence on the drug elution profile. Gamma sterilization modified the drug
      elution profiles of dexamethasone, indomethacin and simvastatin, but had little
      effect on the drug elution profile of ciprofloxacin compared to three other
      drugs.

PMID- 19394907
TI  - Suturing of fragile skin.

PMID- 19394908
TI  - The 'underwire bra' mastopexy: a new option.

PMID- 19394909
TI  - The pudendal thigh flap for vaginal reconstruction: optimising flap survival.
AB  - BACKGROUND: The pudendal thigh fasciocutaneous (PTF) flap is a useful flap in
      perineal reconstruction, that is reliable when small but is traditionally
      unreliable when large flaps are raised. Large flaps in particular, are associated
      with an increased incidence of apical necrosis. Thorough descriptions of the
      vascular anatomy of this flap have been lacking from the literature, with the
      current study evaluating this anatomy, aiming to provide the anatomical basis for
      vascular problems and for techniques to maximise its survival. METHODS: Five
      unembalmed human cadaveric pelvis specimens were studied. Lead oxide injectant
      enabled radiographic and dissection analysis of the arterial anatomy of the
      integument of the perineum. RESULTS: A consistent pattern of vascular supply was
      found in all specimens. 1: the blood supply to the pelvic floor was supplied
      sequentially by the posterior labial/scrotal arteries, cutaneous branches from
      the anterior branch of the obturator artery, and branches from the external
      pudendal arteries. 2: these vessels ran close to the midline, medial to the PTF
      flap. 3: the posterior labial/scrotal arteries were deep to the Colles' fascia
      and the branches from the obturator artery and external pudendal arteries were
      located superficial to the Colles' fascia. CONCLUSION: This study has
      demonstrated that the PTF flap is a three vascular territory flap and that the
      pedicle is situated close to the midline. This may explain why regions of the PTF
      flap may have a potentially precarious blood supply, and suggests that the PTF
      flap should be designed more medially. Given the third territory of supply to the
      apex of the flap, a delay procedure may help to avoid flap necrosis.

PMID- 19394910
TI  - Pectoralis major flap perfusion.

PMID- 19394911
TI  - Surgical correction of pseudoainhum in chronic epidermolysis bullosa: a case
      report.
AB  - Pseudoainhum is a rare condition of unknown aetiology that is characterised by
      the presence of constriction bands of extremities due to a variety of underlying
      causes that progress to irreversible damage and auto-amputation of the affected
      digit. Epidermolysis bullosa is a group of disorders characterised by extremely
      fragile skin and recurrent blister formation resulting from minor mechanical
      trauma. The association of epidermolysis bullosa with other hand defects, such as
      hand contracture and pseudosyndactyly, have been reported; however, ainhum-like
      digital constriction bands have not been reported in association with this
      disorder. To our knowledge, this is the first reported case of pseudoainhum in
      association with epidermolysis bullosa and highlights good surgical response
      obtained with microscopic removal of the recurred constriction band and cross
      finger flap to prevent recurrence, relieve symptoms and improve cosmesis.

PMID- 19394912
TI  - A papule arising in a skin graft--to biopsy or not to biopsy?

PMID- 19394913
TI  - Effect of azotemia on serum N-terminal proBNP concentration in dogs with normal
      cardiac function: a pilot study.
AB  - OBJECTIVES: To evaluate amino-terminal pro-B type natriuretic peptide (NT-proBNP)
      concentration in dogs with renal dysfunction and normal cardiac structure and
      function. ANIMALS: Eight dogs with renal disease, 23 healthy control dogs.
      METHODS: Serum NT-proBNP concentration was measured in healthy dogs and dogs with
      renal disease using an ELISA validated for use in dogs. Affected dogs were
      eligible for inclusion if renal dysfunction was diagnosed based on urinalysis and
      serum chemistry, and if they were free of cardiovascular disease based on
      physical exam, systolic blood pressure, and echocardiography. RESULTS: The
      geometric mean serum NT-proBNP concentration was significantly higher in dogs
      with renal disease (617 pmol/L; 95% CI, 260-1467 pmol/L) than in healthy control
      dogs (261 pmol/L; 95% CI, 225-303 pmol/L; P=0.0014). There was a modest positive
      correlation between NT-proBNP and BUN and creatinine. Median NT-proBNP
      concentration was not significantly different between groups when indexed to BUN
      (median NT-proBNP:BUN ratio; renal, 14.2, IQR, 3.93-17.7 vs. control, 16.3, IQR,
      9.94-21.2; P=0.29) or creatinine (median NT-proBNP:creatinine ratio; renal, 204,
      IQR, 72.6-448 vs. control, 227, IQR, 179-308; P=0.67). CONCLUSION: Dogs with
      renal disease had significantly higher mean serum concentration of NT-proBNP than
      control dogs. Renal function should be considered when interpreting NT-proBNP
      results as concentrations may be falsely elevated in dogs with renal dysfunction
      and normal cardiac function. The effect of renal disease was lessened by indexing
      NT-proBNP to BUN or creatinine. Future studies in dogs with both renal and heart
      disease are warranted.

PMID- 19394914
TI  - Documentation status and parental concerns about development in young US children
      of Mexican origin.
AB  - OBJECTIVE: To examine parent concerns about development, learning, and behavior
      for young children of Mexican origin, and to identify whether these reports
      differ by families' citizenship/documentation status. METHODS: Data come from the
      2005 California Health Interview Survey, a population-based random-digit dial
      telephone survey of California's noninstitutionalized population. California
      Health Inerview Survey (CHIS) investigators completed interviews of 43 020
      households with a total of 5856 children under age 6 years, of whom 1786 were
      reported being of Mexican origin. Developmental risk was measured by parent
      concerns elicited by the Parents' Evaluation of Developmental Status. We used
      bivariate and multivariate analyses to examine associations between developmental
      risk and family citizenship/documentation status (parents are undocumented, at
      least one documented noncitizen parent, or both parents are US citizens) among
      children of Mexican origin and US-born non-Latino white children, after adjusting
      for age, income, parental education, and predominant household language. RESULTS:
      In multivariate analyses, children of Mexican origin did not differ significantly
      from US-born white children in developmental risk (odds ratio 1.12, 95%
      confidence interval 0.88-1.42). In subgroup analyses, children of Mexican origin
      with undocumented parents had higher odds of developmental risk (odds ratio 1.53,
      95% confidence interval 1.00-2.33) than non-Latino white children whose parents
      were citizens, after adjusting for confounders. CONCLUSIONS: Mexican children
      with undocumented parents have greater parent-reported developmental risk than
      Mexican and white children whose parents are US citizens or otherwise legally
      documented. More research is needed to understand the roles of immigration stress
      and home environments on the developmental risks of children in households with
      undocumented parents.

PMID- 19394915
TI  - Primary care and children's mental health in Brazil.
AB  - OBJECTIVE: Primary care offers opportunities to expand children's access to
      mental health (MH) services, but a given practice's community context and staff
      attitudes may influence which integration models are feasible. The aim of this
      study was to explore the possibility of using community-based primary care to
      increase access to MH services in low-income communities in Brazil. METHODS: A
      qualitative study was undertaken using focus groups with adolescents aged 11 to
      16 (n = 46), parents (n = 40), and primary care clinicians and staff (n = 52)
      from public-sector health centers in 6 low-income Brazilian communities chosen
      for their geographic diversity. RESULTS: Parents felt they had little support in
      parenting and attributed much of their children's behavior and mood problems to
      life in violent, poor communities. Parents thought that primary care could
      potentially be a source of MH care, but that clinicians often seemed rushed or
      uninterested. Clinicians classified many child problems as issues with parenting
      rather than MH. Nonprofessional staff was more likely to be a source of support
      to parents, except at one center that had a truly integrated MH service.
      Adolescents reported little need for MH services. CONCLUSIONS: Expanding the role
      of primary care in child MH may require close attention to how parents,
      adolescents, and clinicians define their problems and on the causes to which they
      attribute them. These factors interact with differences in how centers organize
      MH care, and the extent to which they take advantage of patient interactions with
      nonprofessional staff.

PMID- 19394916
TI  - The Valenti technique in the treatment of hallux rigidus.
AB  - INTRODUCTION: Metatarsophalangeal joint osteoarthritis of the great toe (hallux
      rigidus) is a frequent condition for which numerous surgical techniques have been
      proposed. The most used ones are cheilectomy and arthrodesis. The objectives of
      this retrospective study are to present the midterm results of the Valenti
      procedure and to compare these results with those from other recognized surgical
      techniques. MATERIALS AND METHODS: We conducted a retrospective analysis of a
      continuous group of 32 patients (41 cases) presenting hallux rigidus and treated
      using the Valenti technique from November 1999 to July 2004. The mean age of
      these patients at the time of surgery was 57 years. Forty-one percent of these
      patients also presented a static disorder of the foot. One or several additional
      procedures were undertaken, at the time of surgery, in 24% of these cases.
      Patients were assessed using the AOFAS score completed by the walking distance
      test, the gait test, the tiptoe test and self-evaluation of patient satisfaction.
      The radiographic work-up before surgery and at follow-up showed the progression
      of the joint space changes and allowed us to evaluate plantar subluxation at the
      base of the first phalanx under the metatarsal head. RESULTS: Twenty-four
      patients (32 cases) were reviewed and evaluated with a mean follow-up of 5.5
      years. Two cases of reflex sympathetic dystrophy were observed as complications.
      The mean final score was 81 out of 100 from a preoperative score of 47 out of
      100. Pain was absent or only occasional in 94% of the cases. Discomfort wearing
      shoes was absent or moderate in 91% of the cases. Joint range of movement was
      greater than 30 degrees in 72% of the cases and the toes were stable. Walking
      distance was unlimited in 79% of the cases. A mean 30% plantar subluxation at the
      base of the first phalanx was noted at follow-up, with no clinical consequence.
      The results were comparable irrelevantly of the hallux rigidus grade being
      treated. DISCUSSION: The numerous techniques proposed achieve comparable results
      both in terms of pain relief and functional result but each one has its own
      limitations. Only arthroplasties with silastic implants and the Keller technique
      give less satisfactory results. Arthrodesis remains the first-choice treatment
      for advanced hallux rigidus but failure is possible in case of technical error or
      malunion. Cheilectomy, a conservative intervention, is ideal for lesions that are
      not too advanced or remain limited to the dorsal part of the joint; this
      conservative option presents generally no specific complications. Prosthetic
      replacement--with, to date, little long-term experience for total arthroplasty-
      remains controversial because the results deteriorate over time. The Valenti
      procedure exposes the patient to a possible risk of metatarsophalangeal joint
      destabilization if the resection is too great, but this does not impair the final
      functional outcome. CONCLUSION: The arthrectomy described by Valenti is a highly
      reproducible intervention. We find it to be a good compromise between mobility
      and stability, providing good results for all hallux rigidus grades and entailing
      a low complication rate. LEVEL OF CLINICAL EVIDENCE: Level IV. Therapeutic Study.

PMID- 19394917
TI  - Research projects related to complete dentures published in 2008 by members of
      the Japan Prosthodontic Society.
AB  - This article reviews the findings of the original papers related to complete
      dentures published in the Journal of the Japan Prosthodontic Society (Nippon
      Hotetsu Shika Gakkai Zasshi), Vol. 52, 2008. A total of six articles focused on
      complete dentures or materials related to complete dentures were selected and
      summarized. A variety of subjects in relation to removable prosthodontics were
      discussed in the articles, including denture plaque control, resilient denture
      lining materials or denture adhesives, and assessment and/or anatomical analysis
      of prognosis of complete dentures.

PMID- 19394918
TI  - Hemodynamic and functional assessment of mechanical aortic valves using combined
      echocardiography and multidetector computed tomography.
AB  - BACKGROUND: Limitations are found in the ability of transthoracic
      echocardiography to evaluate mechanical aortic valve replacements (AVR). We
      evaluated the ability of combined echocardiography and computed tomography (CT)
      to enhance the hemodynamic and functional evaluation of AVR. METHODS: We
      performed a retrospective evaluation of 41 consecutive patients with AVR (27
      bileaflet, 14 single disc) and both transthoracic echocardiography and 64
      detector electrocardiographic-gated CT. Each study was interpreted by 2
      independent, blinded readers. The effective orifice area was compared with the
      corrected energy-loss coefficient area and the geometric orifice area. Patients
      with an elevated mean pressure gradient (>15 mm Hg) were assessed for potential
      abnormal findings, including patient-prosthesis mismatch, elevated cardiac index,
      valve dysfunction, significant regurgitation, or pressure recovery effect.
      RESULTS: Significant differences (P<0.05) and moderate-to-high correlations
      (r=0.55-0.98) were observed between the effective orifice area (2.2+/-0.8 cm(2)),
      corrected energy-loss coefficient area (3.0+/-1.5 cm(2)), and geometric orifice
      area (3.6+/-0.9 cm(2)). At least one abnormality was observed in 7 of 25 patients
      with normal gradients and in 14 of 16 patients with elevated gradients (P<0.001).
      In 16 patients with elevated mean pressure gradient, a potential cause could be
      determined in 4 with echocardiography alone and in 14 patients with combined
      echocardiography and CT (P=0.001). CONCLUSION: CT aids in the interrogation of
      prosthetic valve function, enhancing evaluation for patient prosthesis mismatch,
      and correction for pressure recovery by the corrected energy-loss coefficient. CT
      is additive to the assessment of mechanical AVR with transthoracic
      echocardiography, and the combination permits a more complete assessment of both
      AVR function and hemodynamics.

PMID- 19394919
TI  - Optimizing CAD diagnosis in China with CT angiography.
AB  - BACKGROUND: Diagnosis of coronary artery disease (CAD) in China with coronary
      angiography (CA) can be challenging because of high disease prevalence and
      limited resources. Coronary computed tomography angiography (CTA) may provide an
      opportunity to minimize invasive diagnostic procedures among intermediate-risk
      patients indicated for CA and increase patient access to diagnosis of CAD in a
      cost-effective manner. OBJECTIVE: This study was conducted to evaluate the
      potential costs and efficiency of using CTA in combination with CA to optimize
      diagnosis and care of patients with suspected CAD in China. METHODS: We conducted
      a cost-consequences analysis from the perspective of Fuwai Hospital in Beijing.
      We developed a decision-analytic model that compared a diagnostic strategy of CA
      only with a strategy of CTA in combination with CA for patients with intermediate
      pretest probability of significant CAD and indicated for CA. RESULTS: In the base
      case analysis, use of CTA in combination with CA led to a cost-savings of US $597
      per patient evaluated compared with the CA-only diagnostic strategy. The hospital
      cost per angiography-confirmed diagnosis of CAD was US $8,103 for CTA followed by
      CA compared with US $9,148 for CA only. The unit cost of CA, and CTA sensitivity
      were the most influential parameters on the results. The range of cost savings
      associated with use of CTA followed by CA was US $768 - US $461 per patient over
      a CAD prevalence range of 14% - 59%. CONCLUSION: The results of our study suggest
      that CTA implementation in China for intermediate-risk patients indicated for CA
      may optimize the patient population that undergoes invasive CA procedures and may
      provide cost savings for Chinese hospitals.

PMID- 19394920
TI  - Gerbode defect.
AB  - Images of a case showing Gerbode defect are presented with transesophageal echo
      correlation.

PMID- 19394922
TI  - On the lawfulness of the decision to terminate memory search.
AB  - Nearly every memory retrieval episode ends with a decision to terminate memory
      search. Yet, no research has investigated whether these search termination
      decisions are systematic, let alone whether they are made consistent with a
      particular rule. In the present paper, we used a modified free-recall paradigm to
      examine the decision to terminate search. Data from two experiments revealed that
      the total time engaged in retrieval was a monotonically increasing function of
      the total number of items retrieved, whereas the time from final retrieval to
      search termination (exit latency) was a monotonically decreasing function of the
      total number of items retrieved. These findings were compared to the predictions
      of previously proposed stopping rules, using the Search of Associative Memory
      framework. Of the four rules examined, only one predicts the obtained data
      pattern.

PMID- 19394921
TI  - Progesterone and medroxyprogesterone acetate differentially regulate alpha4
      subunit expression of GABA(A) receptors in the CA1 hippocampus of female rats.
AB  - The Women's Health Initiative trials - in which more extreme adverse outcomes
      were observed in the medroxyprogesterone acetate (MPA) + conjugated equine
      estrogen (CEE) arm, as compared to the CEE only arm - suggest that the addition
      of MPA to estrogen treatment has undesirable consequences. An important question
      raised by these results is whether the adverse outcomes observed in the progestin
      arm can be attributed to effects that are unique to MPA or are common to all
      progestins. In this study we explored the potential for MPA and progesterone (P4)
      to differentially impact neuroendocrine function by comparing their effects on
      mRNA expression for the alpha4 subunit of GABA(a) receptors in the CA1
      hippocampus of female rats. Prior research has shown that P4, acting through its
      reduced metabolite allopregnanolone (AP), can mediate alpha4 subunit expression,
      thereby altering GABA(A) receptor gated currents. By contrast, MPA competitively
      inhibits the enzymes necessary for the synthesis of AP. In this study,
      ovariectomized females were primed with estradiol benzoate and then treated with
      P4, MPA, or vehicle. Subjects were sacrificed 12 h or 24 h later and in situ
      hybridization was used to measure alpha4 mRNA in the CA1 hippocampus. At 12 h but
      not 24 h, alpha4 mRNA was reduced in the P4 group as compared to the MPA group,
      and as compared to the vehicle group. These results suggest that MPA, while
      progestational in terms of its effects in the uterus, is not a simple substitute
      for P4 in other systems. The relative impact of these two progestins on
      neuroendocrine function must be carefully explored.

PMID- 19394923
TI  - Linear and non-linear parameterization of EEG during monitoring of carotid
      endarterectomy.
AB  - In this paper, new quantitative linear (HLF ratio: high frequency/low frequency
      spectral power ratio) and non-linear parameters (ZC: zero crossing and FD:
      fractal dimension) which can assist the physician in real-time decision whether a
      shunt is required or not during intra-operative EEG monitoring of carotid
      endarterectomy are presented. The results obtained with the new parameters are
      compared with those achieved by other indexes proposed in the literature. The HLF
      ratio and ZC parameters yielded the best results with a 100% of correct
      identification of both shunt and no-shunt situations. The ZC can be also easily
      implemented in the real-time monitoring of EEG.

PMID- 19394924
TI  - Chronic exposure to fine particulate matter emitted by traffic affects
      reproductive and fetal outcomes in mice.
AB  - Air pollution is an important environmental health risk factor that can result in
      many different gestational and reproductive negative outcomes. In this study, we
      have investigated the effects of two different times of exposure (before
      conception and during pregnancy) to urban ambient particulate matter on
      reproductive and pregnancy outcomes in mice. Using exposure chambers receiving
      filtered (F) and non-filtered (NF) air, we observed that exposed females
      exhibited changes in the length of estrus cycle and extended estrus and,
      therefore, a reduction in the number of cycles during the studied period (F 2.6
      +/- 0.22 and NF 1.2 +/- 0.29, p = 0.03). The mean number of antral follicles
      declined by 36% (p = 0.04) in NF mice (75 +/- 35.2) compared to F mice (118.6 +/-
      18.4). Our results further indicate a significant increase in time necessary for
      mating and decreased fertility and pregnancy indices (p = 0.003) in NF couples.
      Mean post-implantation loss rates were increased by 70% (p < or = 0.005) in the
      NF2 group (exposed before and during pregnancy to NF air) compared to the F1
      group (exposed before and during pregnancy to F air) and were influenced by both
      pre-gestational (p < 0.004) and gestational (p < 0.01) period exposure. Fetal
      weight was significantly higher in the F1 group when compared with the other
      groups (p < 0.001), at a 20% higher weight in the F1 group (0.86 +/- 0.18 g) than
      in the NF2 group (0.68 +/- 0.10 g). Furthermore, fetal weight was influenced by
      both pre-gestational and gestational period exposure, and a significant
      interaction between these two factors was found (p < 0.001). This study
      demonstrated that exposure to ambient levels of urban traffic-generated
      particulate matter negatively affects different functions and stages of the
      reproductive process. Our results also reinforce the idea that maternal exposure
      to air pollution is linked to negative pregnancy outcomes, even if the exposure
      occurs only before conception.

PMID- 19394925
TI  - Air pollution exposure and self-reported cardiovascular disease.
AB  - BACKGROUND: Studies suggest that increases of fine particle concentrations
      (PM2.5) could be linked with a rise in cardiovascular disease. With approximately
      25% of American adults aged 30 and older reporting having either heart disease or
      hypertension it is possible that exposure to air pollution could have significant
      public health consequences. This study examined the relationship between PM2.5
      and the prevalence of self-reported hypertension and heart disease using data
      from a large nation-wide survey. STUDY DESIGN: Adults, 30 years of age or older,
      who participated in the National Health Interview Survey (NHIS) from 1999 to 2005
      were linked to annual PM2.5 data from the US Environmental Protection Agency (N =
      132,224). Annual air quality estimates were averaged from monitors within 20
      miles of the respondent's residential block group. Respondents who reported being
      told they had hypertension by a health professional on two or more separate
      occasions were defined as hypertensive. Heart disease was defined as answering,
      "yes" to one or more of three NHIS questions on heart disease. RESULTS: A 10
      microg/m3 increase in PM2.5 exposure was associated with a small elevated risk of
      hypertension (adjusted odds ratio (OR) 1.05, 95% confidence interval (CI) 1.00
      1.10) risk of heart disease (1.08 95% CI 1.00-1.16). The association between
      PM2.5 and hypertension was found in non-Hispanic white adults (OR 1.10 95% CI
      1.04-1.17) but not in non-Hispanic black or Hispanic adults. CONCLUSIONS:
      Findings from this study complement those from other studies and indicate that
      PM2.5 adversely affects cardiovascular health. Our results are consistent with
      other studies in showing a small association between exposure to PM2.5 and
      cardiovascular outcomes.

PMID- 19394926
TI  - Dental morphology and ancestry in Albuquerque, New Mexico Hispanics.
AB  - The term "Hispanic" groups people from Central and South America and the
      Caribbean, combining disparate cultures, languages, and ancestry, and masking
      biological differences. Historical and current admixture patterns within these
      populations and with indigenous and European-, African-, and/or Asian- derived
      populations complicate the biological picture. Although "Hispanic" has little
      biological meaning, it is used widely in epidemiology, disease management, and
      forensics as a biologically significant group. An interdisciplinary approach
      combining historical, cultural, and biological data can characterize regional and
      temporal differences between Hispanic populations. We examined biological
      distances with a population of central New Mexico Hispanics, as a case study of
      the local specificity of population history. We collected dental morphological
      trait frequencies from samples of recent Albuquerque-area Hispanic Americans and
      several ancestral and contemporary groups. To explore regional admixture patterns
      we calculated biological distances using the modified Mahalanobis D(2) statistic.
      Our results indicate that Albuquerque Hispanics are more similar to their
      European and African ancestral groups than to Native Americans in New Mexico.
      Additionally, their affinity to Native Americans is greater with prehistoric
      rather than contemporary samples. We argue that these results reflect a local
      rather than pan-Hispanic admixture pattern; they underscore that populations are
      better understood at the local and regional levels. It is undesirable to make
      sweeping biological generalizations for groups known to be geographically and
      genetically disparate. This research is part of a growing trend in biological
      research concerning Hispanics and other groups-an emphasis on local samples,
      informed by historical, cultural, and biological factors.

PMID- 19394927
TI  - Bispectrum of stator phase current for fault detection of induction motor.
AB  - A number of research studies has shown that faults in a stator or rotor generally
      show sideband frequencies around the mains frequency (50 Hz) and at higher
      harmonics in the spectrum of the Motor Current Signature Analysis (MCSA). However
      in the present experimental studies such observations have not been seen, but any
      fault either in the stator or the rotor may distort the sinusoidal response of
      the motor RPM and the mains frequency so the MCSA response may contain a number
      of harmonics of the motor RPM and the mains frequency. Hence the use of a higher
      order spectrum (HOS), namely the bispectrum of the MCSA has been proposed here
      because it relates both amplitude and phase of number of the harmonics in a
      signal. It has been observed that it not only detects early faults but also
      indicates the severity of the fault to some extent.

PMID- 19394928
TI  - Treatment of displaced supracondylar humeral fractures among children: crossed
      versus lateral pinning.
AB  - This retrospective study evaluated different pinning configurations used in the
      treatment of displaced supracondylar humeral fractures among children, mainly
      regarding maintenance of fracture reduction and avoidance of complications. The
      fractures (41 type II and 67 type III) of 108 children (mean age 6.48 years) were
      treated by closed reduction and percutaneous pinning: 37 with crossed pins, 37
      with two lateral pins and 34 with two lateral and one medial pin. Mean follow-up
      period was 7.4 months. Type III fractures fixed by two lateral pins were found
      significantly prone to postoperative instability, late complications and need for
      medial pin fixation. There was a significant relation between either delay to
      surgery or postoperative instability and occurrence of complications. Final
      outcome was significantly poorer in type III than in type II fractures. Fixation
      by two lateral pins only is not recommended for treating type III supracondylar
      humeral fractures, but could be used initially to fix severely unstable fractures
      to allow extension of the elbow before inserting a medial pin. Every effort
      should be made to avoid iatrogenic ulnar nerve injury while inserting the medial
      pin.

PMID- 19394930
TI  - A reply to: Pull Ter Gunne AF, Aquarius AE, Roukema JA. Risk factors predicting
      mortality after blunt traumatic cervical fracture [Injury 2008;39(12):1437-41].

PMID- 19394931
TI  - Olecranon fractures.
AB  - Several options exist for the management olecranon fractures. These include
      tension band, plate and intramedullary fixation techniques as well as fragment
      excision with triceps advancement and non-operative management. No one technique
      is suitable for the management of all olecranon fractures. In deciding how to
      treat this common trauma presentation, the surgeon needs a good understanding of
      the anatomy, different fracture morphologies, surgical options and potential
      complications. With appropriate management and early mobilisation good functional
      results can be expected in the majority of patients.

PMID- 19394935
TI  - Enjoying life after Injury.

PMID- 19394934
TI  - Israeli hospital preparedness for terrorism-related multiple casualty incidents:
      can the surge capacity and injury severity distribution be better predicted?
AB  - BACKGROUND: The incidence of large-scale urban attacks on civilian populations
      has significantly increased across the globe over the past decade. These
      incidents often result in Hospital Multiple Casualty Incidents (HMCI), which are
      very challenging to hospital teams. 15 years ago the Emergency and Disaster
      Medicine Division in the Israeli Ministry of Health defined a key of 20 percent
      of each hospital's bed capacity as its readiness for multiple casualties. Half of
      those casualties are expected to require immediate medical treatment. This study
      was performed to evaluate the efficacy of the current readiness guidelines based
      on the epidemiology of encountered HMCIs. METHODS: A retrospective study of HMCIs
      was recorded in the Israeli Defense Force (IDF) home front command and the
      Israeli National Trauma Registry (ITR) between November 2000 and June 2003. An
      HMCI is defined by the Emergency and Disaster Medicine Division in the Israeli
      Ministry of Health as >or=10 casualties or >or=4 suffering from injuries with an
      ISS>or=16 arriving to a single hospital. RESULTS: The study includes a total of
      32 attacks, resulting in 62 HMCIs and 1292 casualties. The mean number of
      arriving casualties to a single hospital was 20.8+/-13.3 (range 4-56, median
      16.5). In 95% of the HMCIs the casualty load was <or=52. Based on severity scores
      and ED discharges 1022 (79.2%) casualties did not necessitate immediate medical
      treatment. CONCLUSION: Hospital preparedness can be better defined by a fixed
      number of casualties rather than a percentile of its bed capacity. Only 20% of
      the arriving casualties will require immediate medical treatment. Implementation
      of this concept may improve the utilisation of national emergency health
      resources both in the preparation phase and on real time.

PMID- 19394937
TI  - Pro-atherogenic effects of probucol in apo E-KO mice may be mediated through
      alterations in immune system: Parallel alterations in gene expression in the
      aorta and liver.
AB  - OBJECTIVE: To establish underlying molecular mechanisms of pro-atherogenic
      effects of probucol in apo E-KO mice. METHODS: Affymetrix Gene Chip System,
      GenMAPP/MAPPFinder software and real-time PCR techniques were used to identify
      alterations in gene expression and biological pathways in the liver and aorta of
      both male apo E-KO and male wild-type mice treated with or without probucol (1%,
      w/w) for 18 weeks. Plasma levels of lipids, cytokines, liver function test, and
      the extent of atherosclerosis and liver histology were examined. RESULTS AND
      CONCLUSIONS: Probucol treatment paradoxically reduced plasma cholesterol levels,
      increased plasma cytokine levels and atherogenesis in apo E-KO mice. Three
      hundred and sixty genes/transcripts and 110 biological processes were
      significantly differentially expressed in the liver of probucol-treated apo E-KO
      mice. The response to biotic stimulus, immune response and inflammatory response
      were the most prominent processes expressed in the liver. The expression of 60 of
      these genes involved in immune response including inflammatory responses, antigen
      presentation, humoral immune response, immune cell activation, innate immune
      response, and regulation of immune response was over-expressed. Many of these
      genes were also over-expressed in the aorta of probucol-treated apo E-KO mice.
      Such effects of probucol were not observed in the liver and aorta of wild-type
      mice. A significant interaction between apo E deficiency and probucol treatment
      was observed. Histological examinations showed a significant infiltration of
      inflammatory cells in the liver of probucol-treated apo E-KO mice, but not in
      C57BL/6 mice. These findings suggest that probucol-induced atherogenesis may be
      mediated through a pro-inflammatory state.

PMID- 19394938
TI  - Concerning an oversight.

PMID- 19394941
TI  - Dynamic behaviors of microtubules in cytosol.
AB  - Highly anisotropic microtubules (MTs) immersed in cytosol are a central part of
      the cytoskeleton in eukaryotic cells. The dynamic behaviors of an MT-cytosol
      system are of major interest in biomechanics community. Such a solid-fluid system
      is characterized by a Reynolds number of the order 10(-3) and a slip ionic layer
      formed at the MT-cytosol interface. In view of these unique features, an
      orthotropic shell-Stokes flow model with a slip boundary condition has been
      developed to explore the distinctive dynamic behaviors of MTs in cytosol. Three
      types of motions have been identified, i.e., (a) undamped and damped torsional
      vibration, (b) damped longitudinal vibration, and (c) overdamped bending and
      radial motions. The exponentially decaying bending motion given by the present
      model is found to be in qualitative agreement with the existing experimental
      observation [Felgner et al., 1996. Flexural rigidity of microtubules measured
      with the use of optical tweezers, Journal of Cell Science 109, 509-516 ].

PMID- 19394939
TI  - Fish oil supplementation improves endothelial function in normoglycemic offspring
      of patients with type 2 diabetes.
AB  - OBJECTIVE: Offspring of patients with type 2 diabetes (OPDs) exhibits endothelial
      dysfunction (ED) associated with a chronic inflammatory state. N-3
      polyunsaturated fatty acids (n-3 PUFA) may have antioxidant and anti-inflammatory
      properties that are beneficial for cardiovascular and metabolic health.
      Therefore, in the present study, we tested the hypothesis that dietary
      supplementation with fish oil rich in n-3 PUFA may improve ED in otherwise
      healthy OPDs. METHODS AND DESIGN: A double-blind, placebo-controlled trial was
      conducted with 50 OPDs. Participants were randomized to treatment with either
      placebo or n-3 PUFA (2g/day) for 12 weeks. Before and after treatment we
      evaluated endothelial function (using flow-mediated dilation (FMD) of the
      brachial artery), circulating inflammatory markers (adiponectin, TNF-alpha, and
      high sensitivity-CRP), and insulin resistance (QUICKI). RESULTS: No significant
      changes were observed in study outcomes in subjects treated with placebo. By
      contrast, when compared with baseline values, subjects treated with n-3 PUFA had
      significant improvement in FMD (9.1+/-5.8% vs. 11.7+/-4.4%, p=0.02) that was
      accompanied by decreased plasma triglycerides (117+/-73mg/dl vs. 86+/-44mg/dl,
      p=0.001) and TNF-alpha levels (8.9+/-2.3pg/ml vs. 6.8+/-2.7pg/ml, p=0.001), and a
      trend towards increased plasma adiponectin levels (7.8+/-4.5microg/ml vs. 9.5+/
      5.1microg/ml, p=0.09). When data were analyzed by multiple regression analysis,
      decreased TNF-alpha after treatment with n-3 PUFA predicted increased FMD.
      CONCLUSION: Dietary supplementation with n-3 PUFA significantly improved
      endothelial function and reduced pro-inflammatory markers in OPDs. Thus, fish oil
      consumption may have beneficial cardiovascular and metabolic health effects in
      otherwise healthy subjects predisposed to diabetes and its vascular
      complications.

PMID- 19394942
TI  - Modelling the mechanical response of elastin for arterial tissue.
AB  - We compare two constitutive models proposed to model the elastinous constituents
      of an artery. Holzapfel and Weizsacker [1998. Biomechanical behavior of the
      arterial wall and its numerical characterization. Comput. Biol. Med. 28, 377-392]
      attribute a neo-Hookean response, i.e. Psi=c(I(1)-3)), to the elastin whilst
      Zulliger et al. [2004a. A strain energy function for arteries accounting for wall
      composition and structure. J. Biomech. 37, 989-1000] propose Psi=c(I(1)-3)(3/2).
      We analyse these constitutive models for two specific cases: (i) uniaxial
      extension of an elastinous sheet; (ii) inflation of a cylindrical elastinous
      membrane. For case (i) we illustrate the functional relationships between: (a)
      the Cauchy stress (CS) and the Green-Lagrange (GL) strain; (b) the tangent
      modulus (gradient of the CS-GL strain curve) and linearised strain. The predicted
      mechanical responses are compared with recent uniaxial extension tests on elastin
      [Gundiah, N., Ratcliffe, M.B., Pruitt, L.A., 2007. Determination of strain energy
      function for arterial elastin: experiments using histology and mechanical tests.
      J. Biomech. 40, 586-594; Lillie, M.A., Gosline, J.M., 2007a. Limits to the
      durability of arterial elastic tissue. Biomaterials 28, 2021-2031; 2007b.
      Mechanical properties of elastin along the thoracic aorta in the pig. J. Biomech.
      40, 2214-2221]. The neo-Hookean model accurately predicts the mechanical response
      of a single elastin fibre. However, it is unable to accurately capture the
      mechanical response of arterial elastin, e.g. the initial toe region of arterial
      elastin (if it exists) or the gradual increase in modulus of arterial elastin
      that occurs as it is stretched. The alternative constitutive model (n=32) yields
      a nonlinear mechanical response that departs from recent uniaxial test data
      mentioned above, for the same stretch range. For case (ii) we illustrate the
      pressure-circumferential stretch relationships and the gradients of the pressure
      circumferential stretch curves: significant qualitative differences are observed.
      For the neo-Hookean model, the gradient decreases rapidly to zero, however, for
      n=32, the gradient decreases more gradually to a constant value. We conclude that
      whilst the neo-Hookean model has limitations, it appears to capture more
      accurately the mechanical response of elastin.

PMID- 19394943
TI  - Stability of pulsatile blood flow at the ostium of cerebral aneurysms.
AB  - The strength and direction of blood flow into and within a cerebral aneurysm are
      important issues in developing effective interventional strategies to stabilize
      the aneurysm. We tested the hypothesis that there are significant major
      hemodynamic features that are common to many aneurysm flows of the type studied
      here. This was investigated by performing computational fluid dynamic simulations
      of flow near 7 cerebral aneurysms using geometrical data obtained from clinical
      CT scans. Our numerical simulations of flow across the ostium plane of an
      aneurysm show that in many cases there is relatively stable flow structure that
      is maintained over the phase of the pulsatile flow cycle. The two main features
      of this flow are (1) quasi-permanent regions of flow influx and efflux across the
      ostium plane exist, separated by a "virtual boundary", and (2) a helical vortex
      flow pattern within the aneurismal sac with swirl in two orthogonal cross
      sectional planes. These numerical observations are consistent with in vitro
      experimental data from ultrasound color-Doppler velocimetry and other numerical
      and experimental studies. The observed flow patterns are found to occur in
      different types of aneurysms (bifurcation and sidewall), and can persist even
      after flow parameters are perturbed beyond the normal range of physiological flow
      conditions. These results suggest that in many cases, major aspects of the
      behavior of aneurismal hemodynamics for important classes of aneurysms can be
      learned from an analysis of steady, non-pulsatile flow, which is simpler and
      faster to simulate than time-dependent, pulsatile flow. An understanding of this
      fluid dynamical behavior may also prove useful in the design of stents, coils,
      and various other endovascular flow diverting devices.

PMID- 19394944
TI  - MRI-based assessment of hip joint translations.
AB  - To better understand movement limitations and, to some extent, the pathogenesis
      of osteoarthritis, it is important to quantitatively measure femoroacetabular
      translations to assess if any joint subluxation occurs. In this paper, we aim at
      measuring hip joint displacements from magnetic resonance images (MRI) based on a
      surface registration technique. Because this measurement is related to the
      location of the hip joint center (HJC), we investigate and compare different HJC
      estimation approaches based on patient-specific 3D bone models. We estimate the
      HJC based on a simulated circumduction while minimizing inter-articular distance
      changes. Measurements of femoroacetabular translations during low amplitude
      abductions (80 samples) and extreme flexions (60 samples) in female professional
      dancers, which is a population potentially exposed to femoroacetabular
      impingements, do not show any significant subluxation.

PMID- 19394945
TI  - Unusually high enantioselectivity in high-performance liquid chromatography using
      cellulose tris(4-methylbenzoate) as a chiral stationary phase.
AB  - The cellulose tris(4-methylbenzoate) chiral stationary phase (CSP) (commercially
      known as Chiralcel OJ-H) exhibited an extremely high enantioselectivity when used
      in the HPLC resolution of N-thiocarbamoyl-3-(4'-prenyloxy)-phenyl-5-phenyl-4,5
      dihydro-(1H) pyrazole (Compound 1), in both normal-phase and polar organic
      conditions. Using n-hexane-ethanol (80:20, v/v) as a mobile phase, an
      enantioseparation factor value of 138.5 was found. In order to modulate the
      elution time of the longer retained enantiomer, a simple HPLC procedure was
      developed. The optimized analytical protocol was based on the stopped flow
      technique and did not involve any change in mobile phase composition. The
      stronger interaction energy of the (S) enantiomer compared to that of the (R)
      enantiomer was mainly attributed to the formation of a hydrogen bonding between
      the amino group of the thiocarbamoyl moiety and the carbonyl oxygen of the CSP.

PMID- 19394946
TI  - Application of silver ion in the separation of macrolide antibiotic components by
      high-speed counter-current chromatography.
AB  - Three macrolide antibiotic components - ascomycin, tacrolimus and
      dihydrotacrolimus - were separated and purified by silver ion high-speed counter
      current chromatography (HSCCC). The solvent system consisted of n-hexane-tert
      butyl methyl ether-methanol-water (1:3:6:5, v/v) and silver nitrate (0.10mol/l).
      The silver ion acted as a pi-complexing agent with tacrolimus because of its
      extra side double bond compared with ascomycin and dihydrotacrolimus. This
      complexation modified the partition coefficient values and the separation factors
      of the three components. As a result, ascomycin, tacrolimus and dihydrotacrolimus
      were purified from 150mg extracted crude sample with purities of 97.6%, 98.7% and
      96.5%, respectively, and yields over 80% (including their tautomers). These
      results cannot be achieved with the same solvent system but without the addition
      of silver ion.

PMID- 19394947
TI  - Characterization of O-trimethylsilyl oximes of trisaccharides by gas
      chromatography-mass spectrometry.
AB  - Gas chromatography (GC) data (linear retention indices and relative areas) and
      mass spectra (most representative m/z fragments) of 12 reducing trisaccharides as
      trimethylsilyl oximes (TMSO) and four non-reducing as trimethylsilyl (TMS) ethers
      have been described for the first time and related to their structural features.
      Some trends have been observed: earlier elution of non-reducing compounds and
      fructotrioses; aldotrioses bearing the reducing end with link in position 6
      showing the highest retention. Abundance of several fragment ions and their
      ratios were useful for trisaccharide characterization; some of these features
      seem to be useful for the characterization of new trisaccharides.

PMID- 19394948
TI  - Drastically enhanced photocatalytic activity in nitrogen doped mesoporous TiO2
      with abundant surface states.
AB  - Nitrogen doped mesoporous TiO(2) was prepared via a modified two-step
      hydrothermal route. In contrast to undoped mesoporous TiO(2), nitrogen doped
      mesoporous TiO(2) has superior photocatalytic activity under both UV and visible
      light irradiation. Photoluminescence spectra reveal that nitrogen doped
      mesoporous TiO(2) possesses abundant surface states, which can play a vital role
      in trapping photoinduced carriers as evidenced by photoelectrochemical process
      and prolonging the lifetime of the carriers. The remarkably enhanced
      photocatalytic activity in nitrogen doped mesoporous TiO(2) is attributed to the
      generated abundant surface states.

PMID- 19394949
TI  - Hollow Ni-B amorphous alloy with enhanced catalytic efficiency prepared in
      emulsion system.
AB  - Ni-B nanospheres were synthesized through chemical reduction of nickel ions with
      borohydride in an emulsion system comprised of cyclohexylamine, polyethylene
      glycol, and water. With the characterization of X-ray diffraction, selective area
      electronic diffraction, X-ray photoelectron spectroscopy, and transmission
      electron microscopy, the resulting hollow Ni-B nanospheres were identified to be
      amorphous alloys with a hollow chamber. Cyclohexylamine played a significant role
      in fabricating hollow Ni-B nanospheres, because only solid nanoparticles were
      obtained in the absence of cyclohexylamine. Polyethylene glycol also had a
      significant influence on the formation of hollow Ni-B nanospheres, because low
      yield of hollow nanospheres were achieved without this polymer. During liquid
      phase chloronitrobenzene hydrogenation, the as-synthesized Ni-B catalyst
      exhibited a much higher activity and even better selectivity than the dense Ni-B
      nanoparticles prepared by direct reduction of nickel ions with borohydride.

PMID- 19394950
TI  - TiO2 P-25 anatase rapid precipitation from water by use of struvite formation.
AB  - UV(360nm) irradiation of TiO(2) P-25 nanoparticle in water suspension is used for
      photocatalytic mineralization of pollutants or inactivation of microorganisms.
      Removal of TiO(2) particles from large volumes of water following photocatalytic
      process is problematic due to their nano-size. So far no chemical methods are
      available for TiO(2) rapid precipitation while filtration or centrifugation is
      not feasible because of high cost and limited performance. In the present study
      TiO(2) was rapidly precipitated from water suspension by formation of the mineral
      struvite. Addition of Mg, P, and NH(4)(+) at stochiometric rates of 1:1:1 at
      pH>8.3 resulted in TiO(2) entrapment into struvite formed flocs and rapid
      precipitation. Struvite sludge formed and precipitated was observed under HSEM
      revealing TiO(2) entrapment into struvite mineral.

PMID- 19394951
TI  - Thermodynamics of micellization of imidazolium ionic liquids in aqueous
      solutions.
AB  - The structural similarity between some ionic liquids (ILs) and ionic surfactants,
      indicates that ILs are expected to exhibit surface adsorption and aggregation
      properties. The Krafft temperature and the temperature dependence of the critical
      micelle concentration (CMC) were determined for four imidazolium ionic liquids
      with varying chain length by measuring concentration dependence of electrical
      conductivity at different temperatures. The magnitude of the thermodynamic
      parameters of the micelle formation provide valuable information about the
      driving force of micellization of these compounds, therefore, the parameters of
      these chemicals were estimated from the degree of ionization, and the CMC. The
      thermodynamic parameters were correlated to directly measured values using
      isothermal titration calorimetry (ITC). It was found that the long-chained
      imidazolium ILs show similar thermodynamic characteristics as traditional
      cationic surfactants, whereas the Krafft temperature was shown to be lower than
      that of traditional cationic surfactants of similar chain length.

PMID- 19394952
TI  - Lasting antibacterial activities of Ag-TiO2/Ag/a-TiO2 nanocomposite thin film
      photocatalysts under solar light irradiation.
AB  - Photodegradation of Escherichia coli bacteria in presence of Ag-TiO(2)/Ag/a
      TiO(2) nanocomposite film with an effective storage of silver nanoparticles was
      investigated in the visible and the solar light irradiations. The nanocomposite
      film was synthesized by sol-gel deposition of 30 nm Ag-TiO(2) layer on
      approximately 200 nm anatase(a-)TiO(2) film previously doped by silver
      nanoparticles. Both Ag/a-TiO(2) and Ag-TiO(2)/Ag/a-TiO(2) films were transparent
      with a SPR absorption band at 412 nm. Depth profile X-ray photoelectron
      spectroscopy showed metallic silver nanoparticles with diameter of 30 nm and fcc
      crystalline structure were self-accumulated on the film surface at depth of 5 nm
      of the TiO(2) layer and also at the interface of the Ag-TiO(2) and a-TiO(2) films
      (at depth of 30 nm). Both OH(-) bounds and H(2)O contents were concentrated on
      the film surface and at the interface, as a profit in releasing more ionic (not
      metallic) silver nanoparticles. Antibacterial activity of the nanocomposite film
      against E. coli bacteria was 5.1 times stronger than activity of the a-TiO(2), in
      dark. Photo-antibacterial activity of the nanocomposite film exposed by the solar
      light was measured 1.35 and 6.90 times better than activity of the Ag/a-TiO(2)
      and a-TiO(2), respectively. The main mechanism for silver ion releasing was inter
      diffusion of water and silver nanoparticles through pores of the TiO(2) layer.
      Durability of the nanocomposite film was at least 11 times higher than the Ag/a
      TiO(2) film. Therefore, the Ag-TiO(2)/Ag/a-TiO(2) photocatalyst can be nominated
      as one of the effective and long-lasting antibacterial nanocomposite materials.

PMID- 19394953
TI  - Zinc oxide nanoparticles/glucose oxidase photoelectrochemical system for the
      fabrication of biosensor.
AB  - Nanosized semiconductor crystals can increase efficiency of photochemical
      reactions and greatly improve the catalytic activity of enzymes to generate novel
      photoelectrochemical systems. In this work, glucose oxidase (GOx)/zinc oxide
      (ZnO) is selected as a model system to assess the photovoltaic effect of
      semiconductor nanoparticles on the enzyme electrode. UV-spectrum and circular
      dichroism (CD) results show that the structure of GOx is preserved after
      conjugation with ZnO nanoparticles. The current response of the enzyme electrode
      containing ZnO nanoparticles increases from 0.82 to 21 microA cm(-2) in the
      solution of 10 mM beta-D-glucose. Furthermore, after irradiating the enzyme
      electrode with UV light for 2 h, the current response can be increased nearly 30%
      and the detection limit can be lowered about two orders compared with the
      catalytic reactions in the dark, which indicate that a technique to fabricate a
      novel photocontrolled enzyme-based biosensor may be developed.

PMID- 19394954
TI  - Solution of the agglomerate Brownian coagulation using Taylor-expansion moment
      method.
AB  - The newly proposed Taylor-expansion moment method (TEMOM) is extended to solve
      agglomerate coagulation in the free-molecule regime and in the continuum regime,
      respectively. The moment equations with respect to fractal dimension are derived
      based on 3rd Taylor-series expansion technique. The validation of this method is
      done by comparing its result with the published data at each limited size regime.
      By comparing with analytical method, sectional method (SM) and quadrature method
      of moments (QMOMs), this new approach is shown to produce the most efficiency
      without losing much accuracy. At each limited size regime, the effect of fractal
      dimension on the decay of particle number and particle size growth is mainly
      investigated, and especially in the continuum regime the relation of mean
      diameters of size distributions with different fractal dimensions is first
      proposed. The agglomerate size distribution is found to be sensitive to the
      fractal dimension and the initial geometric mean deviation before the self
      preserving size distribution is achieved in the continuum regime.

PMID- 19394955
TI  - Fabrication of superhydrophobic and heat-insulating antimony doped tin
      oxide/polyurethane films by cast replica micromolding.
AB  - A novel process for fabricating superhydrophobic and heat-insulating polymeric
      nanocomposite films was developed. Briefly, antimony doped tin oxide (ATO)
      nanoparticles that commonly endow coats heat-insulating and transparent functions
      were mixed into commercial waterborne polyurethane (WPU) suspensions to obtain
      ATO/WPU suspensions, which were then cast onto poly(dimethylsiloxane) (PDMS)
      stamps replicated from fresh lotus leaves. After being dried and peeled off from
      stamps, ATO/PU films with superhydrophobic surface and heat-insulating property
      were created, while PU films without ATO only showed high hydrophobicity.
      Scanning electron microscopy (SEM) imaging showed the surface of ATO/PU
      superhydrophobic films had unique micro- and nano-structures similar with those
      on the lotus leaf. On the contrary, no obvious nano-structures were found on the
      surface of pure PU films, demonstrating mixing functional nanoparticles into
      polymers is a necessary and feasible step in creating superhydrophobic and
      functional films by replica molding method.

PMID- 19394956
TI  - Intelligent core-shell nanoparticles and hollow spheres based on gelatin and PAA
      via template polymerization.
AB  - PAA/gelatin nanoparticles, with interpolymer complexes of gelatin and polyacrylic
      acid (PAA) as the cores and gelatin as the shells, were prepared via facile
      polymerization of AA on gelatin template. The morphology change of the
      nanoparticles during the reaction was traced by a combined use of dynamic light
      scattering (DLS) and atomic force microscopy (AFM) techniques, which revealed a
      discrepancy among the structure of the nanoparticles formed at different stages
      of the reaction: as the reaction proceeds, nanoparticles with larger compact
      cores and thinner shells are produced. The resultant nanoparticles are multi
      responsive. Especially, they exhibit a significant temperature-dependent size
      change: upon raising the temperature from 25 degrees C, the nanoparticle size
      decreases monotonically until reaching equilibrium at about 40 degrees C. This
      temperature-dependence of the nanoparticle size was found to be reversible
      provided the nanoparticle solution was cooled at a low temperature (4 degrees C).
      The thermo-sensitivity of the nanoparticles is attributed to the thermo-induced
      sol-gel transition of the gelatin shells. In addition, the nanoparticles were
      further converted to hollow spheres via successive locking the shell structure by
      the reaction of gelatin with cross-linker glutaraldehyde, and cavitation of the
      cross-linked nanoparticles by switching the medium from acidic to neutral. The
      cavitation process was monitored by DLS, which indicated a mass decrease and size
      shrinkage. AFM and transmission electron microscopy (TEM) were used to trace the
      morphology change of the nanoparticles during the cavitation. The hollow
      structure was confirmed by TEM observation.

PMID- 19394957
TI  - Age-related changes in acoustic characteristics of adult speech.
AB  - This paper addresses effects of age and sex on certain acoustic properties of
      speech, given conflicting findings on such effects reported in prior research.
      The speech of 27 younger adults (15 women, 12 men; mean age 25.5 years) and 59
      older adults (32 women, 27 men; mean age 75.2 years) was evaluated for
      identification of differences for sex and age group across measures of
      fundamental and formant frequencies (F0, F1, F2 and F3) and voice onset time
      (VOT). There were significant sex-by-age group interactions for F0, F1, and VOT,
      some of which were specific to individual speech sounds. The findings suggest
      that further research on aging speech should focus on sex differences and the
      potential influence such changes may have on communication abilities of older
      adults with hearing loss. LEARNING OUTCOMES: The reader will be able to
      understand and describe (1) possible changes in specific acoustic properties with
      age, (2) how these changes may differ for women and men, and (3) the potential
      impact these changes may have on the speech understanding of older individuals
      with hearing loss.

PMID- 19394958
TI  - Reduced neuronal expression of insulin-degrading enzyme in the dorsolateral
      prefrontal cortex of patients with haloperidol-treated, chronic schizophrenia.
AB  - Insulin-degrading enzyme (IDE) is a neutral thiol metalloprotease, which cleaves
      insulin with high specificity. Additionally, IDE hydrolyzes Abeta, glucagon, IGF
      I and II, and beta-endorphin. We studied the expression of IDE protein in
      postmortem brains of patients with schizophrenia and controls because: (1) the
      gene encoding IDE is located on chromosome 10q23-q25, a gene locus linked to
      schizophrenia; (2) insulin resistance with brain insulin receptor
      deficits/receptor dysfunction was reported in schizophrenia; (3) the enzyme
      cleaves IGF-I and IGF-II which are implicated in the pathophysiology of the
      disease; and (4) brain gamma-endorphin levels, liberated from beta-endorphin
      exclusively by IDE, have been reported to be altered in schizophrenia. We counted
      the number of IDE immunoreactive neurons in the dorsolateral prefrontal cortex,
      the hypothalamic paraventricular and supraoptic nuclei, and the basal nucleus of
      Meynert of 14 patients with schizophrenia and 14 matched control cases. Patients
      had long-term haloperidol treatment. In addition, relative concentrations of IDE
      protein in the dorsolateral prefrontal cortex were estimated by Western blot
      analysis. There was a significantly reduced number of IDE expressing neurons and
      IDE protein content in the left and right dorsolateral prefrontal cortex in
      schizophrenia compared with controls, but not in other brain areas investigated.
      Results of our studies on the influence of haloperidol on IDE mRNA expression in
      SHSY5Y neuroblastoma cells, as well as the effect of long-term treatment with
      haloperidol on the number of IDE immunoreactive neurons in rat brain, indicate
      that haloperidol per se, is not responsible for the decreased neuronal expression
      of the enzyme in schizophrenics. Haloperidol however, might exert some effect on
      IDE, through changes of the expression levels of its substrates IGF-I and II,
      insulin and beta-endorphin. Reduced cortical IDE expression might be part of the
      disturbed insulin signaling cascades found in schizophrenia. Furthermore, it
      might contribute to the altered metabolism of certain neuropeptides (IGF-I and
      IGF-II, beta-endorphin), in schizophrenia.

PMID- 19394959
TI  - Dose-dependent frontal hypometabolism on FDG-PET in methamphetamine abusers.
AB  - OBJECTIVE: Although a lot of evidence from neuropsychological and neuroimaging
      studies supports the view that patients with substance dependence have
      abnormalities in the prefrontal cortex, functional deficits in the prefrontal
      cortex have not been fully investigated in methamphetamine (MA) dependent
      patients. This study was prepared to examine whether MA abusers have cerebral
      metabolic abnormalities and executive dysfunction. METHOD: Twenty-four abstinent
      MA dependent patients and 21 age-matched control subjects underwent resting brain
      FDG-PET and completed computerized versions of the Wisconsin card sorting test
      (WCST). Resting brain PET images were obtained 30min after an intravenous
      injection of 370MBq of (18)F-FDG. Significant differences in glucose metabolism
      were estimated for every voxel using t-statistics on SPM2 implemented in Matlab.
      RESULTS: Resting brain FDG-PET revealed significant hypometabolism in the left
      inferior frontal white matter (Talairach coordinates (x, y, z): -34, 7, 31) in MA
      dependent patients compared to the control subjects (corrected p=0.001, peak
      Z=5.37, voxel number 201). The nearest gray matter region was the left inferior
      frontal cortex (Brodmann area 9). There were negative correlations between the
      relative regional cerebral metabolism for glucose (rCMRglc) in the left inferior
      frontal white matter and the total cumulative dose of MA (r=-0.57, p<0.01). MA
      dependent patients completed significantly fewer categories (3.8+/-2.2) and made
      more perseveration errors (21.3+/-11.8) and total errors (43.5+/-19.5) on the
      WCST when compared to the control subjects (p<0.01). CONCLUSIONS: These data
      suggest that MA dependent patients have dose-dependent frontal hypometabolism and
      frontal executive dysfunction.

PMID- 19394960
TI  - Reduced amygdala volume in newly admitted psychiatric in-patients with unipolar
      major depression.
AB  - Structural neuroimaging studies investigating amygdala volumes in patients
      suffering from major depression have yielded variable results. Discrepant
      findings across studies may be attributable in part to heterogeneity with respect
      to antidepressant medication and to lack of adequate control for the effects of
      total brain volume and age. Here, 24 unipolar depressed in-patients newly
      admitted to a psychiatric unit and 14 healthy control participants matched for
      age, gender, and years of education underwent quantitative magnetic resonance
      imaging (MRI) toward the end of a one-week washout period. Saliva cortisol was
      measured at 08.00 and at 16.00h in patients during washout. Absolute amygdala
      volumes were significantly reduced in the patient group (by 13% in left amygdala
      and 12% in right amygdala). The effect of reduced amygdala volumes in patients
      remained significant after correction for brain volume (BV) and age. Furthermore,
      amygdala volume measurements in the patient sample showed a significant inverse
      relationship to the number of preceding depressive episodes. In patients,
      severity of disease (baseline HAMD scores) and baseline cortisol levels were not
      related to amygdala volume. This study of a sample of unmedicated depressed in
      patients adds to the small, yet growing, body of evidence linking untreated major
      depression to reduced amygdala volume.

PMID- 19394961
TI  - Evaluation of aFGF/bFGF and FGF signaling pathway in the wall of varicose veins.
AB  - BACKGROUND: Extensive extracellular matrix remodeling of the vein wall is
      involved in varicose veins pathogenesis. The process is controlled by numerous
      factors, including peptide growth factors. The aim of the study was to evaluate
      acidic (aFGF) and basic (bFGF) fibroblast growth factors, their receptor (FGFR)
      and the MAP kinase pathway (ERK 1/2) in the wall of varicose and varicose veins
      complicated by thrombophlebitis, when compared to normal ones. METHODS: Segments
      of normal, varicose, and varicose veins complicated by thrombophlebitis were
      collected during varicose veins surgery in 17 patients. Expression and content of
      aFGF and bFGF were evaluated with Western blot and enzyme-linked immunosorbent
      assay (ELISA) methods, respectively, whereas RT-PCR was employed to assess mRNA
      level of growth factors. Expression of FGFR and ERK 1/2 was examined with Western
      blot method. RESULTS: Increased aFGF expression and content were accompanied by
      increased aFGF mRNA level in the wall of varicose veins. Furthermore,
      alternatively spliced aFGF mRNA was shown in varicose veins complicated by
      thrombophlebitis. Expression, content, and mRNA level of bFGF were comparable in
      the investigated material. FGFR and ERK 1/2 expression was demonstrated in the
      wall of diseased veins, however, without any significant differences in
      comparison with the wall of normal veins. CONCLUSIONS: Overexpressed aFGF in the
      wall of varicose veins via FGFR and the MAP kinase pathway may influence
      expression of enzymes involved in extracellular matrix metabolism and play a role
      in vein wall remodeling, as well as in the disease pathogenesis.

PMID- 19394962
TI  - Transcription factor Nrf2 plays a pivotal role in protection against traumatic
      brain injury-induced acute intestinal mucosal injury in mice.
AB  - BACKGROUND: Traumatic brain injury (TBI) can induce an acute intestinal mucosal
      injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) has a unique role in
      many physiological stress processes, but its contribution to intestinal mucosal
      injury after TBI remains to be determined. MATERIALS AND METHODS: Wildtype Nrf2
      (+/+) and Nrf2 (-/-) deficient mice were subjected to a moderately severe weight
      drop impact head injury. Intestinal mucosal morphological changes, plasma
      endotoxin, intestinal permeability, apoptosis, inflammatory cytokines, and
      antioxidant/detoxifying enzymes were measured at 24 hours after TBI. RESULTS:
      Nrf2 deficient mice were found to be more susceptible to TBI-induced acute
      intestinal mucosal injury, as characterized by the higher increase in gut
      structure damage, plasma endotoxin, intestinal permeability, and apoptosis after
      TBI. This exacerbation of intestinal mucosal injury in Nrf2 deficient mice was
      associated with increased intestinal mRNA and protein expression of inflammatory
      cytokines such as tumor necrosis factor-alpha, interleukin-1beta and interleukin
      6, and with decreased intestinal mRNA expression and activity levels of
      antioxidant and detoxifying enzymes including NAD(P)H: quinone oxidoreductase 1
      (NQO1) and glutathione S-transferase alpha-1 (GST-alpha1), compared with their
      wildtype Nrf2 (+/+) counterparts after TBI. CONCLUSIONS: We show for the first
      time that mice lacking Nrf2 are more susceptible to TBI-induced acute intestinal
      mucosal injury. Our data suggests that Nrf2 plays an important role in protecting
      TBI-induced intestinal mucosal injury, possibly by regulating of inflammatory
      cytokines and inducing of antioxidant and detoxifying enzymes.

PMID- 19394963
TI  - Short passive cooling protects rats during hepatectomy by inducing heat shock
      proteins and limiting the induction of pro-inflammatory cytokines.
AB  - BACKGROUND: Prolonged hepatic warm ischemia during surgery remains a significant
      problem, particularly in the setting of liver resection and reduced remaining
      liver mass. The goal of the present study is to evaluate the effect of passive
      cooling caused by exposure to ambient conditions on hepatic injury in rats during
      warm ischemia followed by hepatectomy. METHODS: The left and median lobes of male
      rats were exposed to 75 min of ischemia under either normothermic (37 degrees C)
      or mildly hypothermic (34 degrees C) conditions. After 75 min of ischemia, the
      right lobe was resected, leaving the animal with only the remaining ischemic
      lobes. Animals were allowed to survive indefinitely or sacrificed at 4 h after
      reperfusion for determination of injury and inflammatory gene expression.
      RESULTS: Survival was already markedly higher in mildly hypothermic rats than
      normothermic rats at 24 h. Short passive cooling for the time course of the
      ischemic event significantly increased the hepatic induction of heat shock
      proteins 70 and 32 (both 3-fold versus normothermia, P<0.05) in response to
      ischemia/reperfusion whereas it significantly decreased the induction of tumor
      necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2)
      in the liver. Biochemical markers of hepatic injury were significantly lower in
      the passive cooling group than in normothermic animals: aspartate
      aminotransferase (AST) serum concentrations were 9277+/-3461IU/L versus 15106+/
      4104IU/L (P<0.01), and alanine aminotransferase (ALT) levels 5986+/-2246IU/L
      versus 9429+/-3643IU/L (P<0.01). CONCLUSION: We demonstrated in a clinically
      relevant model of hepatic ischemia/reperfusion that mild hypothermia
      significantly reduces hepatic injury and improves survival.

PMID- 19394965
TI  - Effect of Dakin's solution on components of a dermal equivalent.
AB  - BACKGROUND: The use of Dakin's solution on open wounds remains controversial in
      clinical practice. Here we investigated the effect of Dakin's solution on
      collagen degradation and fibroblast migration using a dermal equivalent.
      MATERIALS AND METHODS: Acid solubilized or neutralized collagen was combined with
      four dilutions of Dakin's solution (0.5%, 0.25%, 0.125%, 0.0125%), with and
      without serum, at room temperature and 37 degrees C. Collagen degradation was
      examined at 0, 1, and 24 h using 8% SDS-page gels. Cell migration was determined
      using dermal equivalents where fibroblasts were incorporated into 3D collagen
      gels and exposed to Dakin's solution with and without serum. The cells were
      assessed for viability and cell migration at 24 and 48 h. RESULTS: Dakin's at
      0.0125% resulted in little or no collagen degradation compared with a higher
      concentration of 0.5%, where collagen was either partially or completely
      degraded. Likewise, cell migration was completely inhibited at higher
      concentrations, while fibroblasts in a 3D matrix at 0.0125% were still able to
      migrate at 24 and 48 h, albeit in fewer numbers compared with controls. Serum had
      a protective effect for both collagen degradation and cell migration when added
      together with the Dakin's solutions. A time and temperature dependent effect was
      also noted, with longer contact and higher temperatures being more detrimental.
      CONCLUSIONS: Collagen degradation and fibroblast migration is affected by the
      concentration of Dakin's solution, the presence or absence of serum, time
      exposure and temperature. Use of Dakin's solution in clinical settings should
      take these findings into consideration in clinical practice.

PMID- 19394964
TI  - Preoperative plasma adiponectin level is a risk factor for postoperative
      infection following colorectal cancer surgery.
AB  - BACKGROUND: Adiponectin is produced exclusively by adipose tissues. It is
      associated with visceral adiposity and various metabolic disorders, and acts as
      an anti-inflammatory protein that inhibits nuclear factor-kappaB activation. The
      purpose of this study is to clarify the association between the preoperative
      plasma adiponectin levels and the development of postoperative infection
      following colorectal cancer surgery. METHODS: Peripheral blood samples were
      collected from 41 colorectal cancer patients before surgery and on postoperative
      days (PODs) 1, 3, 5, and 7. Plasma adiponectin, leptin, and serum C-reactive
      protein (CRP) levels were measured and the white blood cells (WBCs) were counted.
      Subcutaneous and visceral fat volumes were quantified by preoperative CT scans.
      The patients were divided into a group with postoperative infections and an
      uninfected group. RESULTS: In both groups, the postoperative plasma adiponectin
      levels decreased transiently and then gradually recovered. However, the infected
      group had significantly lower adiponectin levels throughout the perioperative
      period than the uninfected group. Logistic regression analysis revealed that
      preoperative adiponectin level was an independent risk factor for postoperative
      infection. CONCLUSIONS: Preoperative adiponectin levels may be useful for
      anticipating the development of postoperative infection following colorectal
      cancer surgery.

PMID- 19394966
TI  - Sustained reversal of diabetes following islet transplantation to striated
      musculature in the rat.
AB  - BACKGROUND: There is an increasing emphasis in the islet transplant community on
      the development of alternative sites for islet implantation. Striated musculature
      constitutes a potential alternative, which has been successfully employed in
      autotransplantation of parathyroid glands for decades. In the present study, a
      technique for intramuscular islet transplantation was developed and compared with
      intraportal islet transplantation in a syngeneic rat model. MATERIALS AND
      METHODS: Lewis rats were used. Pancreata were digested using Liberase. Islets
      were either transplanted into m. biceps femoris in a pearls-on-a-string fashion
      or intraportally, and the ability to reverse diabetes was compared. Eight weeks
      after transplantation an IVGTT was performed. Real-time quantitative RT-PCR was
      employed on muscle biopsies to investigate mRNA levels of cytokines in response
      to the transplant procedure. Explanted livers, muscles, and pancreata were
      harvested at the end of the experiment for histopathological analyses. RESULTS:
      2000 IEQ repeatedly cured diabetic rats at the intraportal site, while 4000 IEQ
      was required at the intramuscular site. Time to reversal of diabetes, post
      transplant weight development, and IVGTT curves did not differ between the
      groups. Normoglycemia was sustainable to the end of the study (>100 days) for all
      animals. The transplant procedure upregulated pro-inflammatory cytokines (IL-6
      and IL-8) in striated muscle, and peri-islet fibrosis was observed in
      intramuscular grafts. CONCLUSIONS: Islet transplantation into striated
      musculature is feasible; however, in its present form the intramuscular site is
      less efficient compared with the liver in rats. The intramuscular site allows
      manipulation of the graft and implantation site prior to transplantation and may
      therefore have implications for islet transplantation in humans.

PMID- 19394967
TI  - Inhibition of growth in medullary thyroid cancer cells with histone deacetylase
      inhibitors and lithium chloride.
AB  - BACKGROUND: While representing only 3% of thyroid malignancies, medullary thyroid
      cancer (MTC) accounts for 14% of thyroid cancer deaths. MTC has a high rate of
      recurrence and lacks effective treatments. The histone deacetylase (HDAC)
      inhibitors valproic acid (VPA) and suberoyl bis-hydroxamic acid (SBHA) activate
      the Notch1 signaling pathway, while lithium chloride inhibits the glycogen
      synthase kinase-3ss (GSK-3ss) pathway. These compounds have been shown to limit
      growth and suppress hormonal secretion; thus, targeting different signaling
      pathways may be an effective treatment. METHODS: MTC cells were treated with
      varying combinations of up to 20 mM lithium chloride with either 3 mM VPA or 20
      muM SBHA for 48 h. Western analysis was used to measure the effects on Notch1,
      GSK-3ss, and neuroendocrine (NE) markers. Growth was assessed by a
      methylthiazolyldiphenyl-tetrazolium (MTT) bromide cellular proliferation assay.
      Western analysis was used to determine the mechanism of growth regulation.
      RESULTS: Combination therapy increased active Notch1, inhibited the GSK-3ss
      pathway, and decreased NE markers. Additive inhibition of growth was observed
      with combination therapy. Lower-dose combination therapy achieved greater
      decreases on NE markers and growth than treatment with any of the drugs alone.
      Moreover, an increase in the cleavage of the apoptotic markers caspase-3 and PARP
      was observed. CONCLUSIONS: Combination therapy with lithium chloride and HDAC
      inhibitors suppresses NE markers and decreases growth via apoptosis of MTC cells
      in vitro. With the possibility of increased efficacy and decreased toxicity,
      combination therapy may represent a new strategy to treat MTC.

PMID- 19394968
TI  - Protective effect of reduced glutathione and venous systemic oxygen persufflation
      on rat steatotic graft following liver transplantation.
AB  - BACKGROUND: The aim of this study is to explore the protective effect of high
      dose reduced glutathione (GSH) preconditioning and venous systemic oxygen
      persufflation (VSOP) on rat steatotic liver grafts following transplantation.
      METHODS: Steatotic liver model was established by feeding rats a high-fat, high
      cholesterol diet, and infusing stomach with 50% alcohol (1 mL/100g body weight/d)
      for 6 wk. In the pretreated group, short-term and high-dose of GSH administration
      and VSOP were performed. In rat orthotopic liver transplantation model, the
      recipient survival, liver function, hepatic microcirculation blood flow, hepatic
      redox, hepatocytes apoptosis and necrosis, and hepatic ultrastructure alteration
      were observed. RESULTS: In the pretreated rat steatotic grafts, hepatic GSH (from
      29.43 +/- 4.83 to 41.56 +/- 8.51mg/mgprot), superoxide dismutase (SOD) (from
      48.32 +/- 6.27 to 67.74 +/- 7.68 NU/mgprot), and adenosine triphosphate (ATP)
      (from 1.61 +/- 0.20 to 2.28 +/- 0.09 micromoles/g) were significantly increased
      (P < 0.05), whereas malondialdehyde (MDA) was significantly decreased (from 7.20
      +/- 2.18 to 4.63 +/- 0.58 nmol/mgprot, P < 0.05). The hepatocyte necrosis of
      fatty liver graft was significantly reduced in the pretreated group when compared
      with non-treated fatty ones (37.71% +/- 9.69% versus 16.63% +/- 5.53%; t = 3.777,
      P = 0.014), and significantly improved liver function and hepatic ultrastructure
      were observed in the pretreated fatty liver group after operation. The animal
      survival after transplanted with fatty liver was significantly improved (chi(2) =
      4.07, P = 0.0436). CONCLUSION: A short course pretreatment with high-dose GSH and
      oxygen persufflation during cold preservation effectively protect steatotic liver
      grafts from ischemic damage and significantly improve early survival rate in a
      rat fatty liver transplantation model.

PMID- 19394969
TI  - Connecting white matter injury and thalamic atrophy in clinically isolated
      syndromes.
AB  - Previous studies suggest that thalamic degeneration is prominent in multiple
      sclerosis (MS) and even in pre-MS patients presenting with a clinically isolated
      syndrome (CIS). However, the relationships between white matter lesions and deep
      grey matter loss are not well understood. We analyzed the association between
      white matter lesions and the thalami in CIS patients to determine if connectivity
      is an important determinant. We studied 24 CIS patients and 18 normal controls
      with anatomical and diffusion tensor (DTI) MRI images. DTI fiber tracking was
      used to create probabilistic templates of the thalamocortical white matter and to
      define white matter connecting lesions and thalami. DTI metrics in the lesions
      and normal-appearing white matter (NAWM) regions were compared between CIS and
      controls, and correlated with thalamic volume changes estimated by voxel-based
      morphometry. There was 10 times higher density of lesions in thalamocortical
      compared to other brain white matter. Increased diffusivities and decreased
      fractional anisotropies were measured in the thalamocortical NAWM of CIS patients
      compared to controls. A step-wise regression analysis demonstrated that
      thalamocortical lesion volume and the mean diffusivity in track regions
      connecting lesion and thalami were significantly correlated with thalamic volumes
      in patients (Rsq=0.66, p<0.001), a finding not observed in regions outside the
      thalamocortical white matter. These results provide compelling evidence for a
      direct relationship between white matter lesions and thalamic atrophy in CIS
      patients.

PMID- 19394970
TI  - Multisequence-imaging protocols to detect cortical lesions of patients with
      multiple sclerosis: observations from a post-mortem 3 Tesla imaging study.
AB  - Neocortical lesions (NLs) are an important component of multiple sclerosis (MS)
      pathology and may account for part of the physical and cognitive disability.
      Visualizing NLs of patients with MS using magnetic resonance imaging (MRI) poses
      several significant challenges. We optimized the inversion time (TI) of T(1)
      based magnetization-prepared rapid acquisition gradient-echo (MPRAGE) images by
      suppressing the signal of the lesions and enhancing their appearance as
      hypointensities, on the basis of the derived quantitative T(1) measurements. The
      latter were achieved by the means of 2D inversion recovery fast spin echo (IR
      FSE), repeated using different inversion times (TI). Comparisons of detection of
      NLs by MPRAGE and dual echo T(2) weighted (T(2)W) and proton density (PD) W. Four
      coronal brain slices from a deceased MS patient and two coronal brain slices from
      two formerly healthy donors were imaged using a 3 Tesla magnet (3 T) equipped
      with a multi-channel coil. Based upon the averaged T1 values computed from the MS
      specimen as well as visual inspection, an optimal TI of 380 ms was selected for
      the MPRAGE image. No NLs were seen in the specimens of the two healthy donors. Of
      the 40 total NLs observed, 8 (20%) were visible in all three sequences employed.
      Three (7.5%) NLs were visible only in the PDW image and 5 (12.5%) were seen only
      in the T(2)W image. Four NLs (10%) had clearly unique conspicuity in the MPRAGE
      image. Of those, 3 were retrospectively scored in the PDW image (1 NL) or in the
      T2W image (2 NLs). We conclude that for the detection of MS-related NLs, high
      resolution T(1)-based MPRAGE and T(2)-W images offer complementary information
      and the combination of the two image sequences is crucial for increasing the
      sensitivity of detecting MS-induced NLs.

PMID- 19394971
TI  - Main meiofauna taxa as an indicator for assessing the spatial and seasonal impact
      of fish farming.
AB  - The present study aimed to establish potential indicators of fish farming
      pollution in muddy substrate, by means of meiofauna, and to test whether the
      effect of the fish farm is more important to determine the meiofauna community
      than the seasonal environmental conditions. Sampling was performed in spring,
      after several months of light feeding, and in summer, at high food supply.
      Samples were collected in three directions at various distances from the floating
      cages. Harpacticoid copepods and kinorhynchs, whose abundance decreased under the
      cages, were put forward as indicator taxa. However, harpacticoid copepods were
      sensitive to fish farm only, while kinorhynchs showed responsiveness to fish farm
      and to seasonal environmental conditions. Total meiofauna density was dependent
      on season sensu stricto. The nMDS clearly showed a 'cage community' and 'control
      community' in both sampling occasions; therefore it is a good tool for impact
      assessment.

PMID- 19394972
TI  - [Long-term follow-up of patients with gastric antral vascular ectasia treated
      with argon plasma coagulation].
AB  - BACKGROUND AND OBJECTIVE: Due to its easy use and low complication rates, argon
      plasma coagulation (APC) it is most common method of endoscopic treatment for
      gastric antral vascular ectasia (GAVE). We analyze both the long term
      effectiveness of APC for the treatment of GAVE and its side effects. MATERIAL AND
      METHODS: A retrospective review of GAVE patients treated with APC and followed up
      for a minimum of 24 months was done. RESULTS: Eighteen patients (mean age 67,16+/
      13,53; 11 women) were included. Five initially presented with acute bleeding and
      13 with anemia. GAVE eradication was achieved over 3.38+/-1,4 sessions per
      patient. There were no major complications. Five patients had mild bleeding and
      11 complained of abdominal pain, that was self-limited during treatment. Seven
      patients relapsed (39%); 3 of them with melenae and 4 with anemia. Two patients
      with hypergastrinemia developed hyperplastic polyps. No differences were found
      between relapsers and non-relapsers. CONCLUSIONS: APC is a safe and effective
      technique for the treatment of GAVE. The recurrence rates increase gradually over
      time. Early action on recurrence would require improved clinical follow-up and
      blood test monitoring.

PMID- 19394973
TI  - Inverse associations between muscle mass, strength, and the metabolic syndrome.
AB  - The metabolic syndrome (MetS) is a clustering of individual cardiovascular
      disease risk factors, which doubles the risk of early mortality. The authors'
      aimed to determine the prevalence and population attributable risk (PAR%) of the
      MetS among men according to demographic, physical, and lifestyle risk factors. A
      cross-sectional study was conducted in 1195 men in the Florey Adelaide Male
      Ageing Study, a regionally representative cohort of Australian men aged 35 to 81
      years conducted in 2002-2005 (response rate, 45.1%). Prevalent MetS was
      determined according to the Adult Treatment Panel III (ATPIII) and International
      Diabetes Federation (IDF) classifications; and an extensive list of demographic,
      physical (including muscle strength, body composition by dual-energy x-ray
      absorptiometry, sex hormones), and lifestyle factors was accounted for.
      Prevalence estimates were 37.7% and 41.8% for ATPIII and IDF classifications.
      Odds ratios for present MetS were determined using multiple-adjusted logistic
      regression. Odds for present ATPIII MetS decreased (in order of importance) for
      lower insulin and increased for lower muscle mass, lower strength, and 3+ medical
      conditions. Odds for present IDF MetS decreased for lower insulin and increased
      for lower muscle mass, strength, and sex hormone-binding globulin levels; older
      age; and being married. Significant PAR% due to lowest insulin, muscle mass, and
      strength quarters were -44%, 27%, and 17% for the ATPIII Met, and -48%, 31%, and
      20% for the IDF MetS. A substantial proportion of MetS cases would have been
      theoretically prevented if prior exposure to low muscle mass and strength were
      eradicated (PAR% ranged from 14% to 24%). Findings indicate that insulin
      resistance is a central abnormality in the MetS and that muscle mass and strength
      are strong protective factors independent of insulin resistance and abdominal fat
      accumulation. If confirmed prospectively, increases in muscle mass and strength
      needed to prevent a substantial proportion of MetS cases would be achievable with
      a short-term strength training intervention.

PMID- 19394974
TI  - Metabolic disorders induced by highly active antiretroviral therapy and their
      relationship with vascular remodeling of the brachial artery in a population of
      HIV-infected patients.
AB  - Antiretroviral therapy has positively modified the natural history of HIV
      infection; but this treatment can induce metabolic abnormalities, including
      dyslipidemia, fat redistribution, high blood pressure, and insulin resistance.
      The metabolic syndrome, a clustering of the metabolic disorders, is frequently
      detected among HIV patients, especially those on antiretroviral treatment. All
      the arteries can modify their diameter in response to a chronic injury. This
      process, defined vascular remodeling, was demonstrated for the brachial artery.
      It is well known that the diameter of the brachial artery was correlated with the
      number of the elements of the metabolic syndrome and was associated with the
      severity of coronary artery disease. On this basis, we postulate that brachial
      arterial enlargement may be a process potentially correlated with the metabolic
      disorders induced by antiretroviral therapy. We tested this hypothesis in a large
      population of HIV-infected patients in which we measured brachial artery
      diameter, as an indicator of artery remodeling, by noninvasive, ultrasonographic
      technique. Our population consisted of 570 patients, with a mean age of 46.3 +/-
      7.1 years. All the patients were chronically treated with highly active
      antiretroviral therapy. Brachial artery diameter was correlated with insulin
      resistance, evaluated by the homeostasis model assessment of insulin resistance
      index (r = 0.18, P < .0001). There was a significant linear increase in brachial
      artery diameter as the number of components of the metabolic syndrome increased:
      brachial artery diameter for those with 0, 1, 2, 3, or + characteristics was 39.3
      +/- 7.2, 41.0 +/- 6.8, 42.0 +/- 7.3, and 43.8 +/- 7.9 mm, respectively (P < .001
      for trend). In multivariable logistic regression analysis, brachial artery
      diameter was independently correlated with the presence of metabolic syndrome.
      Our results are in line with the hypothesis that, among HIV-infected patients
      chronically treated with antiretroviral therapy, those with a larger brachial
      artery diameter are at high risk for metabolic disorders, including a more severe
      insulin resistance and the presence of metabolic syndrome.

PMID- 19394975
TI  - Resting energy expenditure in subjects with and without intermittent
      claudication.
AB  - Subjects with peripheral arterial disease and intermittent claudication have
      ischemia of the lower extremities, but little is known how this influences
      resting energy expenditure. The objective of the study was to compare the resting
      energy expenditure of subjects with and without intermittent claudication. One
      hundred six subjects limited by intermittent claudication and 77 controls who did
      not have peripheral arterial disease and intermittent claudication participated
      in this study. Subjects were assessed on resting energy expenditure, body
      composition, ankle/brachial index (ABI), and calf blood flow. Subjects with
      intermittent claudication had a lower resting energy expenditure (1585 +/- 251 vs
      1716 +/- 277 kcal/d, P = .019), higher body fat percentage (33.4% +/- 10.7% vs
      29.6% +/- 7.7%, P = .016), higher fat mass (29.6 +/- 10.6 vs 24.2 +/- 8.9 kg, P =
      .011), and lower ABI (0.66 +/- 0.20 vs 1.19 +/- 0.12, P < .001). Resting energy
      expenditure was predicted by fat-free mass (P < .001), ABI (P = .027), and calf
      blood flow (P = .040). Resting energy expenditure remained lower in the subjects
      with intermittent claudication after adjusting for clinical characteristics plus
      fat-free mass (1611 +/- 171 vs 1685 +/- 209 kcal/d, P = .035), but was no longer
      different between groups after further adjustment for ABI and calf blood flow
      (1622 +/- 165 vs 1633 +/- 185 kcal/d, P = .500). Subjects with intermittent
      claudication have lower resting energy expenditure than controls, which is
      partially explained by ABI and calf blood flow.

PMID- 19394976
TI  - Direct comparison among oral hypoglycemic agents and their association with
      insulin resistance evaluated by euglycemic hyperinsulinemic clamp: the 60's
      study.
AB  - The aim of the study was to compare the long-term effect of 4 antidiabetic
      treatment protocols on insulin resistance evaluated by euglycemic
      hyperinsulinemic clamp in type 2 diabetes mellitus patients. Two hundred seventy
      one type 2 diabetes mellitus patients with poor glycemic control and who were
      overweight were enrolled in this study. Patients were randomized and titrated to
      take pioglitazone, metformin, pioglitazone + metformin, or glimepiride +
      metformin for 15 months. They underwent a euglycemic hyperinsulinemic clamp at
      baseline, after 3 months, and after 15 months. Anthropometric and metabolic
      measurements were assessed at baseline, after 3 months, and after 15 months.
      There was a decrease in glycated hemoglobin in all groups, but glycated
      hemoglobin value was lower in the group treated with pioglitazone + metformin
      compared with the groups treated with metformin alone and with pioglitazone
      alone. There was a decrease in fasting plasma glucose and postprandial plasma
      glucose values in all groups, but values obtained with pioglitazone + metformin
      were lower compared with values in the groups treated with metformin alone and
      with pioglitazone alone. Fasting plasma insulin and postprandial plasma insulin
      values were higher in the group treated with glimepiride + metformin compared
      with the other groups. After 15 months, glucose infusion rate and total glucose
      requirement values observed in the groups treated with pioglitazone alone and
      with pioglitazone + metformin were higher compared with the values in the group
      treated with metformin alone and with glimepiride + metformin; furthermore,
      values obtained in the group treated with pioglitazone + metformin were higher
      than the value obtained with pioglitazone alone. Pioglitazone-metformin-based
      therapeutic control is associated with the most quantitatively relevant
      improvement in insulin resistance-related parameters, whereas the sulfonylurea
      metformin-including protocol has less relevant effects.

PMID- 19394977
TI  - Effects of adiponectin transgenic expression in liver of nonalcoholic
      steatohepatitis model mice.
AB  - We have previously reported that transgenic mice expressing nuclear sterol
      regulatory element-binding protein 1c (nSREBP-1c) in adipose tissue under the
      control of aP2 promoter, an inherited lipodystrophic model with insulin
      resistance and fatty liver, developed with age liver lesions similar to those of
      human nonalcoholic steatohepatitis (NASH). Because the spontaneous NASH model
      mice had marked hypoadiponectinemia, here we assessed the effect of adiponectin
      transgenically expressed in the liver of nSREBP-1c transgenic mice. The nSREBP
      1c/adiponectin double-transgenic mice showed hepatic adiponectin production and
      restored circulating adiponectin levels. Both subtypes of adiponectin receptors
      proved to be expressed normally in the liver. Peroxisome proliferator-activated
      receptor-alpha was up-regulated in the double-transgenic mice. Histologic
      findings similar to those observed in the liver specimens of patients with NASH
      were observed in the livers from nSREBP-1c transgenic mice at the age of 30
      weeks. In contrast, the NASH-like hepatic lesions were obviously attenuated in
      age-matched double-transgenic mice. Immunoreactivity of 8-hydroxy-2'
      deoxyguanosine and proliferating cell nuclear antigen-positive cells were
      increased in nSREBP-1c transgenic mice, but not in the double-transgenic mice.
      Postload plasma glucose levels were significantly lower in the double-transgenic
      mice compared with nSREBP-1c transgenic mice, whereas serum leptin levels did not
      differ significantly in the 2 groups. These observations suggest that
      hypoadiponectinemia plays a key role in the pathogenesis of NASH associated with
      insulin resistance and may provide a clue to the novel therapy for human NASH.

PMID- 19394978
TI  - Metabolic rate and fuel utilization during sleep assessed by whole-body indirect
      calorimetry.
AB  - The purpose of this study was to examine metabolic rate and substrate oxidation
      during sleep in relation to time of sleep and sleep stage. Twelve male subjects
      free from sleep-disordered breathing slept for 469 +/- 8.7 (mean +/- SE) minutes
      until natural awakening in a whole-body indirect calorimeter, and
      polysomnographic documentation of sleep was recorded. Energy expenditure
      decreased during the first half of the night, reached a nadir (a 35% decrease),
      and remained relatively stable until awakening. Similarly, fat oxidation
      decreased from the onset of sleep. On the other hand, carbohydrate oxidation
      showed no remarkable changes from the onset of sleep but began to increase before
      awakening. Because distribution of sleep stages is not uniform throughout the
      night, with rapid-eye-movement (REM) sleep tending to appear later in the sleep,
      effect of sleep stage on energy metabolism was isolated by analysis of covariance
      with time as a covariate. Subsequent comparison of metabolic rate by 1-way
      analysis of variance with Bonferroni post hoc analysis revealed that energy
      expenditure during REM sleep was significantly greater than that during sleep
      stages 2 and 3/4 (stage 2, 25.248 +/- 0.961; stage 3/4, 24.825 +/- 0.935; REM,
      25.712 +/- 0.928 kcal kg(-1) fat-free mass d(-1)). Carbohydrate oxidation during
      REM sleep was significantly greater than that during sleep stage 3/4 (stage 3/4,
      12.229 +/- 1.071; REM, 13.986 +/- 1.291 kcal kg(-1) fat-free mass d(-1)).
      Respiration quotient was statistically different among sleep stages, but
      Bonferroni post hoc analysis failed to identify significant differences (stage 2,
      0.850 +/- 0.010; stage 3/4, 0.846 +/- 0.011; REM, 0.861 +/- 0.013). The increases
      in energy expenditure and carbohydrate oxidation during REM sleep are consistent
      with a notion that changes in energy metabolism in brain are manifested as small
      fluctuations in whole-body energy metabolism during sleep.

PMID- 19394979
TI  - A numerical deconvolution method to estimate C-peptide secretion in humans after
      an intravenous glucose tolerance test.
AB  - Quantitative assessment of pancreatic insulin secretion rate in individuals may
      help advance our understanding and treatment of diabetes. We describe for the
      first time the application of a long-established numerical deconvolution
      procedure in which a prescribed input function is used to represent first-phase
      pancreatic secretion response to an intravenous glucose challenge (intravenous
      glucose tolerance test [IVGTT]) in individual subjects. We identify that C
      peptide secretory response to an IVGTT can be described by a basal secretion rate
      (S(b)) (picomoles per liter per minute) and a first-phase secretory response
      characterized by a Gaussian function. The Gaussian function contains 3
      parameters: P(1) (picomoles per liter per minute), which represents the peak rate
      secretion; P(2) (per square minute), which is related to the inverse of peak
      width at half-peak height; and P(3) (minutes), which is the time of the peak
      secretion rate. When applied to data from 8 healthy Chinese subjects, the
      estimated parameter values (mean +/- SD) were 19.2 +/- 12.9 pmol L(-1) min(-1),
      1548 +/- 1143 pmol L(-1) min(-1), 1.09 +/- 1.21 min(-2), and 2.94 +/- 1.13
      minutes for S(b), P(1), P(2), and P(3), respectively. The Gaussian input
      functions are shown to have similar shapes and to be highly concordant in
      magnitude with secretory responses estimated by means of the method of Eaton et
      al (1980) and by the ISEC computer program. In conclusion, we have presented a
      simple, integrated, validated, and easily implemented method suitable for
      quantifying pancreatic C-peptide and insulin secretion in individual human
      subjects. The superiority of our method in comparison with other methods is that
      it uses as an input function the Gaussian, which has been experimentally verified
      as describing in vivo the profile of pulsatile insulin secretion. The particular
      strength of our method is that the Gaussian parameters and simple indices derived
      from them provide a standardized and interpretable means for carrying out
      comparative investigations aimed at quantifying how pancreatic secretory
      responses to an IVGTT differ in various demographic groups or in response to
      therapeutic treatments.

PMID- 19394981
TI  - Repellent activity of alligator pepper, Aframomum melegueta, and ginger, Zingiber
      officinale, against the maize weevil, Sitophilus zeamais.
AB  - The repellent activity of alligator pepper, Aframomum melegueta, and ginger,
      Zingiber officinale (Zingiberaceae), against the maize weevil, Sitophilus zeamais
      (Coleoptera: Curculionidae), was investigated in four-way olfactometer bioassays.
      Results showed that vacuum distilled A. melegueta and Z. officinale extracts were
      repellent towards adult S. zeamais both in the absence and the presence of maize,
      Zea mays, grains. Bioassay-guided liquid chromatographic fractionation of the
      distillates showed that fractions containing oxygenated compounds accounted for
      the repellent activity. Coupled gas chromatography-mass spectrometry (GC-MS),
      followed by GC peak enhancement and enantioselective GC using authentic
      compounds, identified 3 major compounds in the behaviourally active fractions of
      A. melegueta and Z. officinale to be (S)-2-heptanol, (S)-2-heptyl acetate and (R)
      linalool in a ratio of 1:6:3, and 1,8-cineole, neral and geranial in a ratio of
      5.48:1:2.13, respectively. The identification of these behaviourally active
      compounds provides the scientific basis for the observed repellent properties of
      A. melegueta and Z. officinale, and demonstrates the potential for their use in
      stored-product protection at the small-scale farmer level in Africa.

PMID- 19394980
TI  - Serum fatty acid binding protein 4, free fatty acids, and metabolic risk markers.
AB  - Fatty acid binding protein (FABP) 4 chaperones free fatty acids (FFAs) in the
      adipocytes during lipolysis. Serum FFA relates to metabolic syndrome, and serum
      FABP4 is emerging as a novel risk marker. In 36 overweight/obese women, serum
      FABP4 and FFA were measured hourly during 5-hour oral glucose tolerance test.
      Insulin resistance was determined using frequently sampled intravenous glucose
      tolerance test. Serum lipids and inflammation markers were measured at fasting.
      During oral glucose tolerance test, serum FABP4 decreased by 40%, reaching its
      nadir at 3 hours (from 45.3 +/- 3.1 to 31.9 +/- 1.6 ng/mL), and stayed below the
      baseline at 5 hours (35.9 +/- 2.2 ng/mL) (P < .0001 for both, compared with the
      baseline). Serum FFA decreased by 10-fold, reaching a nadir at 2 hours (from
      0.611 +/- 0.033 to 0.067 +/- 0.004 mmol/L), then rebounded to 0.816 +/- 0.035
      mmol/L at 5 hours (P < .001 for both, compared with baseline). Both fasting FABP4
      and nadir FABP4 correlated with obesity. Nadir FABP4 correlated also with insulin
      resistance parameters from frequently sampled intravenous glucose tolerance test
      and with inflammation. Nadir FFA, but not fasting FFA, correlated with the
      metabolic syndrome parameters. In conclusion, fasting FABP4 related to metabolic
      risk markers more strongly than fasting FFA. Nadir FABP4 and nadir FFA measured
      after glucose loading may provide better risk assessment than the fasting values.

PMID- 19394982
TI  - Steroidal saponins from the whole plants of Agave utahensis and their cytotoxic
      activity.
AB  - Phytochemical investigation of the whole plants of Agave utahensis Engelm.
      (Agavaceae) has resulted in the isolation of 15 steroidal saponins (1-15),
      including five spirostanol saponins (1-5) and three furostanol saponins (11-13).
      Structures of compounds 1-5 and 11-13 were determined by spectroscopic analysis
      and the results of hydrolytic cleavage. The isolated compounds were evaluated for
      their cytotoxic activity against HL-60 human promyelocytic leukemia cells.

PMID- 19394983
TI  - Triterpenoid saponins from a cytotoxic root extract of Sideroxylon foetidissimum
      subsp. gaumeri.
AB  - Evaluation of the cytotoxicity of an ethanolic root extract of
      Sideroxylonfoetidissimum subsp. gaumeri (Sapotaceae) revealed activity against
      the murine macrophage-like cell line RAW 264.7. Systematic bioassay-guided
      fractionation of this extract gave an active saponin-containing fraction from
      which four saponins were isolated. Use of 1D ((1)H, (13)C, DEPT135) and 2D (COSY,
      TOCSY, HSQC, and HMBC) NMR, mass spectrometry and sugar analysis gave their
      structures as 3-O-(beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl)-28-O
      (alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-->4)]-beta-D
      xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)
      16alpha-hydroxyprotobassic acid, 3-O-beta-D-glucopyranosyl-28-O-(alpha-L
      rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-
      >4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha
      hydroxyprotobassic acid, 3-O-(beta-D-glucopyranosyl-(1-->6)-beta-D
      glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-
      >4)[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl)-16alpha-hydroxyprotobassic acid, and the known compound, 3-O
      beta-D-glucopyranosyl-28-O-(alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl
      (1-->4)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl)-protobassic acid. Two further saponins were obtained from the
      same fraction, but as a 5:4 mixture comprising 3-O-(beta-D-glucopyranosyl)-28-O
      (alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)[beta-D
      apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)
      16alpha-hydroxyprotobassic acid and 3-O-(beta-D-apiofuranosyl-(1-->3)-beta-D
      glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-
      >4)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl)-16alpha-hydroxyprotobassic acid, respectively. This showed
      greater cytotoxicity (IC(50)=11.9+/-1.5 microg/ml) towards RAW 264.7 cells than
      the original extract (IC(50)=39.5+/-4.1 microg/ml), and the saponin-containing
      fraction derived from it (IC(50)=33.7+/-6.2 microg/ml).

PMID- 19394984
TI  - Fungal transformation of isosteviol lactone and its biological evaluation for
      inhibiting the AP-1 transcription factor.
AB  - A number of hydroxylated diterpenoids were obtained from the microbial
      transformation of isosteviol lactone (4alpha-carboxy-13alpha-hydroxy-13,16-seco
      ent-19-norbeyeran-16-oic acid 13,16-lactone) (2) with Mucorrecurvatus MR 36,
      Aspergillusniger BCRC 31130, and Absidiapseudocylindrospora ATCC 24169.
      Incubation of 2 with M. recurvatus and Asp.niger led to isolation of seven known
      compounds (1 and 3-8). Incubation of 2 with Abs. pseudocylindrospora produced 5
      and six previously unreported compounds (9-14). The structures of these isolated
      compounds were deduced by high-field NMR techniques ((1)H, (13)C, DEPT, COSY,
      NOESY, HSQC, and HMBC), and those of 9 and 11 were further confirmed by X-ray
      crystallographic analyses. Subsequently, the inhibitory effects on activator
      protein-1 (AP-1) activation in lipopolysaccharide-stimulated RAW 264.7
      macrophages of all of these compounds were evaluated. Compounds 2-5, 8, 9, 11,
      and 12 exhibited significant inhibitory activity, while 3 was more potent than
      the reference compound of dexamethasone.

PMID- 19394985
TI  - [Brain tuberculomas: six cases].
AB  - INTRODUCTION: Despite the resurgence of tuberculosis, partly due to HIV
      infection, central nervous system involvement remains rare, accounting for only 2
      to 5% of all tuberculosis forms. PATIENTS ET METHOD: We report six cases of brain
      tuberculomas occurring in patients free of HIV infection and hospitalized between
      2001 and 2006 in the internal medicine department of a Tunisian military hospital
      (Tunis). RESULTS: Four patients had an underlying defect. Headache, fever,
      consciousness disorders, deficit disorder or cerebellar syndrome are the main
      symptoms. Tuberculomas were multiple and disseminated in four cases and localized
      in the brain stem in two cases. Positive diagnosis could be established in two
      cases on the basis of the pathology results of a brain biopsy or detection of
      Mycobacterium tuberculosis in the cerebrospinal fluid; the diagnosis was
      presumptive in the other cases. Five patients recovered under antituberculosis
      treatment maintained on average 13 months (11 to 16 months). Steroid treatment
      was associated in five patients and tapered off for four to six weeks. One 78
      year-old diabetic patient died in a context of cachexia with multiple organ
      failure.

PMID- 19394986
TI  - [Epilepsy with absence status: A new syndrome of idiopathic generalized
      epilepsy].

PMID- 19394987
TI  - [Place of local thrombolytic therapy in the treatment for cerebral venous
      thrombosis].
AB  - INTRODUCTION: Cerebral venous thrombosis (CVT) is uncommon with a variable
      clinical presentation and an unpredictable outcome. Heparin is used for first
      line treatment in association with symptomatic and etiologic management. Despite
      adequate anticoagulation, the condition may deteriorate in some patients
      warranting the use of local thrombolysis (LT) known for good efficacy and safety.
      But there are few cases and trials upon which to base guidelines for the use of
      LT. METHODS: A retrospective review of the medical and radiological records of
      patients with CVT was managed in the Caen hospital over a six-year period. We
      compared clinical factors of poor prognosis and radiological findings according
      to treatment delivered. RESULTS: Thirty-six patients are treated for CVT. LT was
      performed in eight of them; dose-adjusted intravenous heparin was the only
      treatment in the 28 others. Good outcome was achieved in two thirds of the
      patients with functional sinus patency in all cases. Based on an analysis of the
      radiological data of the 36 patients, we propose a summary of radiological risk
      factors associated with a worsening condition despite adequate anticoagulation.
      DISCUSSION/CONCLUSION: Based on our experience and a review of the literature
      which includes 98 previous cases, LT appears to be a relative effective end safe
      procedure even in the presence of a hemorrhagic infarct. The treatment by LT
      should be considered in patients who present clinical criteria of gravity and
      radiological risk factors associated with failure of heparin treatment. The
      usefulness of LT remains to be determined in a randomized trial comparing heparin
      alone and heparin associated with LT.

PMID- 19394988
TI  - [Polymyositis revealing a Sjogren's syndrome].
AB  - INTRODUCTION: Near 10 to 20% of patients with myositis have another systemic,
      sometimes inaugural, disease. CASE REPORT: A 48-year-old woman was admitted with
      progressive hypoesthesia in V2 and V3 areas on both sides, difficulties to chew
      and swallow and then, proximal and axial muscular deficiency, with weight loss.
      Brain MRI showed gadolinium-enhanced trigeminal nerves and biological tests
      revealed anti-SSA and anti-Pm/Scl antibodies and a grade IV in Chisholm scoring
      system on the labial salivary gland biopsy. Neurophysiological studies revealed a
      myogenic pattern on tibialis anterior muscles and a muscle biopsy confirmed the
      diagnosis of polymyositis. CONCLUSION: The diagnosis of primitive Sjogren's
      syndrome was suspected because of the association of bilateral trigeminal
      neuropathy and anti-SSA and anti-Pm/Scl antibodies.

PMID- 19394989
TI  - Microfinance against malaria: impact of Freedom from Hunger's malaria education
      when delivered by rural banks in Ghana.
AB  - A community randomized pre-test/post-test design was used to compare the
      knowledge and behaviors of microfinance clients receiving malaria education
      (n=213) to those receiving diarrhea education (n=223) and to non-client controls
      (n=268). Comparisons assessed differences at follow-up as well as within-group
      changes over time. At follow-up, malaria clients had significantly better malaria
      knowledge than comparison groups: 48.4% of malaria clients were able to identify
      groups most vulnerable to malaria compared with 39.2% of diarrhea clients
      (P=0.044) and 37.7% of non-clients (P=0.024). Malaria clients were more likely
      than diarrhea clients (P=0.024) (P<0.001) and non-clients (P=0.028) (P=0.004) to
      report that insecticide-treated nets (ITNs) provide the best protection against
      malaria, and to agree that pregnant women should use ITNs, respectively. Between
      baseline and follow-up, malaria clients were most likely to: improve in knowledge
      of malaria complications during pregnancy; to own at least one bed net; and to
      report at least one child or woman of reproductive age sleeping under a bed net.
      Malaria clients also experienced the greatest increases in ITN ownership/use (9%
      vs. 2.9% and 6.7% among diarrhea clients and non-clients). Results indicate that,
      although significant barriers to malaria control remain, a malaria education
      program provided by microfinance institutions can effectively contribute to
      community and national malaria initiatives.

PMID- 19394990
TI  - Improved awareness of Pap smear may not affect its use in Nigeria: a case study
      of female medical practitioners in Enugu, southeastern Nigeria.
AB  - Improved awareness of Pap test by Nigerian women may not necessarily increase its
      use. This hypothesis was tested using female medical practitioners in Enugu
      state, Nigeria. They were expected to be advocates of disease screening and
      therefore should lead by example. All respondents were aware of the Pap smear but
      only 18% had used it. The mean frequency of Pap smear was 1.8+/-1.2 (range 1-5).
      Repeat Pap tests were observed only among respondents that had screened as
      routine. The majority (32%) of those who never screened for cervical cancer had
      no reason. There may be more to the use of Pap smear among women in Nigeria than
      its awareness.

PMID- 19394991
TI  - The development and evaluation of a single step multiplex PCR for simultaneous
      detection of Anopheles annularis group mosquitoes, human host preference and
      Plasmodium falciparum sporozoite presence.
AB  - The Anopheles annularis group mosquitoes, subgenus Cellia Theobald (Diptera:
      Culicidae), includes five recognized species: An. annularis Van der Wulp, An.
      nivipes Theobald, An. pallidus Theobald, An. philippinensis Ludlow and An.
      schueffneri Stanton. From these five, the three most common species found in
      Orissa were considered for this study because of their remarkable vectorial and
      behavioral variation and the important role they play in malaria transmission. To
      identify and understand their role in malaria transmission we developed a single
      multiplex PCR-based assay. This assay included the detection of human blood
      feeding habit and Plasmodium falciparum sporozoite presence. Of the 186 An.
      annularis mosquitoes collected, morphological character-based identification
      showed that 94 were An. annularis, 54 were An. philippinensis and 38 were An.
      pallidus. However, the multiplex PCR assay confirmed that 91 were An. annularis,
      56 were An. philippinensis and 39 were An. pallidus individuals after adjustments
      were made for misidentified specimens in the morphological method. Anopheles
      annularis and An. philippinensis were found positive for human blood, and two
      samples of An. annularis species were positive for P. falciparum sporozoites.
      This one-step PCR-based method constitutes a very powerful tool in large surveys
      of anopheline populations.

PMID- 19394992
TI  - Ultrasound triggered cell death in vitro with doxorubicin loaded poly lactic-acid
      contrast agents.
AB  - Traditional chemotherapy generally results in systemic toxicity, which also
      limits drug levels at the area of need. Two ultrasound contrast agents (UCA),
      with diameters between 1-2 microm in diameter and shell thicknesses of 100-200
      nm, composed of poly lactic-acid (PLA), one loaded by surface adsorption and the
      other loaded by drug incorporation in the shell, were compared in vitro for
      potential use in cancer therapy. These poly lactic-acid (PLA) UCA platforms
      contain a gas core that in an ultrasound (US) field can cause the UCA to
      oscillate or rupture. Following a systemic injection of drug loaded UCA with
      external application of US focused at the area of interest, this platform could
      potentially increase drug toxicity at the area of need, while protecting healthy
      tissue through microencapsulation of the drug. In vitro toxicity in MDA-MB-231
      breast cancer cells of the surface-adsorbed and shell-incorporated doxorubicin
      (Dox) loaded UCA were examined at 5 MHz insonation using a pulse repetition
      frequency of 100 Hz at varying pressure amplitudes. Both platforms resulted in
      equivalent cell death compared to free Dox and US when insonated at peak positive
      pressure amplitudes of 1.26 MPa and above. While no significant changes in cell
      death were seen for surface adsorbed Dox-UCA with or without insonation, cell
      death using the platform with Dox incorporated within the shell increased from
      16.12% to 25.78% (p=0.0272), approaching double the potency of the platform when
      insonated at peak positive pressure amplitudes of 1.26 MPa and above. This
      mechanism is believed to be the result of UCA rupture at higher insonation
      pressure amplitudes, resulting in more exposed drug and shell surface area as
      well as increased cellular uptake of Dox containing polymer shell fragments. This
      study has shown that a polymer UCA with drug housed within the shell may be used
      for US-triggered cell death. US activation can be used to make a carrier
      significantly more potent once in the area of need.

PMID- 19394993
TI  - Complete viral genome sequence and discovery of novel viruses by deep sequencing
      of small RNAs: a generic method for diagnosis, discovery and sequencing of
      viruses.
AB  - We report the first identification of novel viruses, and sequence of an entire
      viral genome, by a single step of high-throughput parallel sequencing of small
      RNAs from diseased, as well as symptomless plants. Contigs were assembled from
      sequenced total siRNA from plants using small sequence assembly software and
      could positively identify RNA, ssDNA and dsDNA reverse transcribing viruses and
      in one case spanned the entire genome. The results present a novel approach which
      cannot only identify known viral pathogens, occurring at extremely low titers,
      but also novel viruses, without the necessity of any prior knowledge.

PMID- 19394994
TI  - Host switch during evolution of a genetically distinct hantavirus in the American
      shrew mole (Neurotrichus gibbsii).
AB  - A genetically distinct hantavirus, designated Oxbow virus (OXBV), was detected in
      tissues of an American shrew mole (Neurotrichus gibbsii), captured in Gresham,
      Oregon, in September 2003. Pairwise analysis of full-length S- and M- and partial
      L-segment nucleotide and amino acid sequences of OXBV indicated low sequence
      similarity with rodent-borne hantaviruses. Phylogenetic analyses using maximum
      likelihood and Bayesian methods, and host-parasite evolutionary comparisons,
      showed that OXBV and Asama virus, a hantavirus recently identified from the
      Japanese shrew mole (Urotrichus talpoides), were related to soricine shrew-borne
      hantaviruses from North America and Eurasia, respectively, suggesting parallel
      evolution associated with cross-species transmission.

PMID- 19394995
TI  - CD44 microbeads accelerate HIV-1 infection in T cells.
AB  - Super-paramagnetic CD44 MicroBeads (Miltenyi) designed for the isolation of
      infectious HIV-1 from dilute or difficult biological samples dramatically enhance
      the infectivity of bound HIV virions, even if the original viral suspension is
      merely incubated with beads. Infection of the CEM T cell line with the NL4-3
      virus clone or primary human CD4 T cells with X4- and R5-tropic clones and a
      clade C primary virus isolate all showed accelerated p24 production and larger
      fractions of infected target cells. Effects could be detected very early;
      incubation of virus with the CD44 MicroBeads promoted higher levels of viral
      integration within the first infection cycle. In summary, CD44 MicroBeads provide
      the means not only to concentrate dilute viral samples, but also to directly
      facilitate within days rather than weeks the in vitro expansion of patient
      isolates independent of coreceptor usage and the performance of HIV replication
      assays that require a large fraction of infected primary T cells.

PMID- 19394996
TI  - Metals in liver and kidneys and the effects of chronic exposure to pyrite mine
      pollution in the shrew Crocidura russula inhabiting the protected wetland of
      Donana.
AB  - Historically impacted by anthropogenic activities, the nature reserve of Donana
      (SW Spain) was affected by an unprecedented spillage of mud and acidic water from
      the Aznalcollar pyrite mine in April 1998. Although several studies have
      addressed the influence of this spill on soils, water, and biota, there is little
      information on mammals, especially carnivorous species. We measured the
      concentrations of Fe, Mg, Pb, Hg, Cd, Zn, Cu, Mn, Mo, Co, and Cr in specimens of
      the greater white-toothed shrew, Crocidura russula, inhabiting the protected area
      affected by the mine spillage. We also examined other parameters to approach at
      the physiological effects of pollution. We found an increase in non-essential
      metals (Pb, Cd, and Hg), and morphometric, histological and genotoxic
      alterations. Age and gender were two significant factors explaining metal
      bioaccumulation: adults had higher Hg and Cd levels than juveniles, whereas males
      bioaccumulated more Pb and Co and less Mo than females. The micronucleus
      frequencies in blood erythrocytes were significantly higher in specimens from the
      polluted site than animals from the control site. Shrews from the impacted area
      also had hepatic alterations, namely increased liver-body ratio, focal necrosis,
      and signs of apoptosis in hepatocytes. Due to the relevance of small mammals in
      the diet of endangered species such as carnivorous birds and mammals, the
      findings of our study are of practical use for the management of the Donana
      wildlife reserve and other protected Mediterranean wetlands.

PMID- 19394997
TI  - Degradation of phenol by the collapse of microbubbles.
AB  - This study focuses on the application of microbubble collapse technique to the
      wastewater treatment. We have verified that collapsing air microbubbles lead to
      the decomposition of phenol, a common pollutant. A reduction in phenol of
      approximately 60% was observed during a 2-h test period when air was used as the
      microbubble source. We have also studied the dependence of phenol degradation on
      the pH of the solution and the type of gas within the microbubbles. The pseudo
      first-order kinetic constant for the degradation of phenol, k, increased linearly
      with the concentration of H(+) in solution. The use of oxygen microbubbles gave
      rise to the highest k value (1.6h(-1)) measured. It is suggested that hydroxyl
      radicals play an important role in the phenol decomposition process. The acquired
      information would be useful for the future application of microbubbles in the
      field of wastewater treatment.

PMID- 19394998
TI  - Quantitative structure-property relationships (QSPR) for steroidal compounds of
      environmental importance.
AB  - A quantitative structure-property relationships (QSPR) study was carried out for
      17 steroidal compounds using calculated molecular descriptors and measured
      properties. The utility of calculated molecular descriptors and properties was
      evaluated and improved in some instances by subgroup classification of these 17
      compounds into estrogens and androgens. The calculated values for the octanol
      water partition coefficient (logK(ow)) were found to be in good agreement with
      the measured values for all 17 compounds, whilst good agreement between the
      calculated and measured values for aqueous solubility (logS) was found only for
      the subgroup of androgens. Good linear relationships (R(2)0.782) were found
      between measured logK(ow) values and three molecular descriptors (logFOSA,
      hydrophobic component of the total solvent accessible surface area; logFISA,
      hydrophilic component of the total solvent accessible area and logPSA, Van de
      Waals surface area of polar nitrogen and oxygen atoms). For the measured logS
      values, only weak correlations with molecular descriptors were observed
      (R(2)0.505). The coefficient of logS in the relationship with the hydrophobic
      parameter (logFOSA) was negative but positive with the hydrophilic parameters
      (logFISA and logPSA). Conversely with logK(ow) the opposite was found. These
      observations are in accord with the effects of molecular polarity on aqueous
      solubility.

PMID- 19394999
TI  - The anatomy and systematic position of the early Miocene proconsulid from Meswa
      Bridge, Kenya.
AB  - A small collection of fossil catarrhines was recovered from the early Miocene
      locality of Meswa Bridge in western Kenya between 1978 and 1980. The associated
      fauna from Meswa Bridge indicates an age older than 20 Ma. Much of the material
      has been briefly described previously, and its taxonomic status considered. The
      material can be assigned to a minimum of four individuals, all of which are
      infants or juveniles. Although the specimens were shown to belong to a distinct
      species of Proconsul, the taxon was not named, primarily because many of the
      specimens belonged to immature individuals. Nevertheless, the combined
      morphological features of the deciduous and permanent teeth allow the diagnosis
      of a new species of Proconsul, which is formally named here as P. meswae. It is a
      large-sized species, similar in dental size to P. nyanzae. The main features
      distinguishing it from all other previously named species of Proconsul are:
      incisors and deciduous incisors relatively low crowned; upper deciduous canines
      relatively higher crowned and more robust; molars and deciduous premolars
      relatively broader and higher crowned, with a more pronounced degree of
      buccolingual flare and better developed cingula; size differential between molars
      not as marked; dP(4) with a longer mesial fovea and smaller hypoconulid and
      distal fovea; P(4) relatively broader, with a better developed buccal cingulum;
      lower molars less rectangular with a longer mesial fovea, smaller distal fovea,
      more restricted talonid basin, and a tendency for a smaller hypoconulid; dP(4)
      and upper molars with strongly buccolingually splayed roots; mandibular corpus in
      infants relatively deeper and more slender; maxilla with a well developed canine
      jugum and fossa. The broader and more flared molars with better developed cingula
      indicate that the Meswa Bridge species is more primitive than other species of
      Proconsul. The inference that it is a stem member of the Proconsul clade is
      consistent with the estimated age of the material.

PMID- 19395000
TI  - Evaluation of soil biological activity after a diesel fuel spill.
AB  - Diesel fuel contamination in soils may be toxic to soil microorganisms and plants
      and acts as a source of groundwater contamination. The objective of this study
      was to evaluate the soil biological activity and phytotoxicity to garden cress
      (Lepidium sativum L.) in a soil polluted with diesel fuel. For this, a diesel
      fuel spill was simulated on agricultural soil at dose 1 l m(-2). During the
      experiment (400 days) the soil was not covered in vegetation and no agricultural
      tasks were carried out. A stress period of 18 days following the spill led to a
      decrease in soil biological activity, reflected by the soil microbial biomass and
      soil enzymatic activities, after which it increased again. The n-C(17)/Pristine
      and n-C(18)/Phytane ratios were correlated negatively and significantly with the
      dehydrogenase, arylsulphatase, protease, phosphatase and urease activities and
      with the soil microbial biomass during the course of the experiment. The beta
      glucosidase activity indicated no significant connection with the parameters
      related with the evolution of hydrocarbons in the soil. Finally, the germination
      activity of the soil was seen to recover 200 days after the spill.

PMID- 19395001
TI  - Assessment of human health risks posed by consumption of fish from the Lower
      Passaic River, New Jersey.
AB  - The Lower Passaic River (LPR) in New Jersey has been impacted by variety of human
      activities over the course of the last two centuries. In this risk assessment, we
      assessed potential human health risks associated with consumption of fish from
      the LPR, the human exposure pathway of greatest concern when addressing
      contaminated sediments. Our risk assessment incorporates fish consumption
      information gathered during a year-long, intercept-style creel angler survey and
      representative fish tissue concentrations for 156 chemicals of potential concern
      (COPCs) obtained from USEPA's public database (OurPassaic website:
      http://www.ourpassaic.org/projectsites/premis_public/index.cfm?fuseaction=contami
      ants). Due to the large number of COPCs investigated, this risk assessment was
      divided into two phases: (1) identification of COPCs that contribute to the
      majority of overall excess cancer risk and hazard estimates using deterministic
      and probabilistic methods, and (2) probabilistic characterization of risk using
      distributions of chemical concentration and cooking loss for those compounds
      identified in Phase 1. Phase 1 relied on point estimates of COPC concentrations
      and demonstrated that PCDD/Fs and PCBs (dioxin-like and non-dioxin-like) are the
      greatest contributors to cancer risk, while non-dioxin-like PCBs are the primary
      contributors to non-cancer hazard estimates. Total excess cancer risks for adult
      and child and receptors estimated in Phase 1 were within USEPA's acceptable
      excess cancer risk range, with the exception of RME child (3.0 x 10(-4) and 1.3 x
      10(-4) for deterministic and probabilistic approaches, respectively). Phase 2
      focused on PCDD, PCDF, and PCBs and used distributions of chemical concentrations
      in fish. The results showed that all excess cancer risk estimates were within the
      acceptable risk range, although non-cancer hazard estimates for PCBs slightly
      exceeded a Hazard Index of 1. This HHRA of LPR fish ingestion represents the most
      comprehensive evaluation conducted to date, and demonstrates that measured
      concentrations of COPCs are not likely to pose a health risk to people who
      currently consume fish from the LPR.

PMID- 19395002
TI  - Fate characterization of a novel herbicide ZJ0273 in aerobic soils using multi
      position 14C labeling.
AB  - ZJ0273, propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate, is a
      novel herbicide being developed for use on rape crops. The environmental behavior
      and fate of ZJ0273, however, are not well understood. In this study, multi
      position (14)C-labeled compounds (B-ZJ0273 and C-ZJ0273) were used to investigate
      the fate of ZJ0273 in aerobic soils, and compare their differences in extractable
      residues (ER), bound residues (BR), and mineralization. ER for both (14)C labels
      followed a similar dissipation trend in the same soil, and results showed a
      strong effect of soil pH, with the ER level being significantly higher in acidic
      soils than neutral or alkaline soils. The disappearance of parent compound
      followed first-order dynamics for both labels in the same soils. No difference in
      BR was observed between the two (14)C-labels. BR increased with time and reached
      17.5-35.3% of applied (14)C in the three soils after 100-d incubation, which is
      much smaller than the non-accumulative criteria (70%) as stated in the directives
      by the Commission of the European Communities. Mineralization to CO(2) also
      depended closely on the soil type, with the cumulative mineralized fraction being
      substantially greater in the neutral and alkaline soils than in the acidic soil.
      Results also showed that cumulative mineralization rates of the two labels in the
      acidic soil were much smaller than those in the neutral and alkaline soils.
      Mineralization of C-ZJ0273 (1.2-9.9%) was found to be more extensive than that of
      B-ZJ0273 (0.5-6.6%), suggesting that benzyl ring was more susceptible to cleavage
      than pyrimidine ring. The use of multi-position labeling proved to be valuable;
      it served the purpose of validating the rigorousness of experimental protocols,
      and provided insights into the behavior and fate of the different molecular
      fragments.

PMID- 19395003
TI  - Epidemiology of nephrolithiasis in personnel returning from Operation Iraqi
      Freedom.
AB  - OBJECTIVES: To examine the epidemiology of urolithiasis in personnel returning
      from deployment to Southwest Asia. METHODS: A survey-based study of personnel
      returning from deployment to Southwest Asia was performed. The demographics were
      compared between the personnel reporting a history of urolithiasis during or
      within the first 90 days of returning from deployment and the personnel without a
      history of reported urolithiasis. RESULTS: A total of 10,180 personnel were
      demobilized and 6153 surveys were received during a 9-month period, for a survey
      response rate of 60%. Of the personnel returning survey, 1% reported urolithiasis
      during their deployment. The personnel who reported urolithiasis were slightly
      older than those who did not (32.6 vs 29 years old, P < .00038). The odds of
      reporting urolithiasis during deployment were 30.9 times greater for personnel
      with a history of stone disease and 2.4 times greater for those with a family
      history of stone disease. No difference was found in the rates of urolithiasis
      with regard to sex or race. Also, no strong evidence for an association between
      the rates of reported urolithiasis and seasonal variations in temperature in
      Southwest Asia was found. CONCLUSIONS: The rate of reported urolithiasis among
      deployed personnel was lower than that in the general population. The personnel
      who reported urolithiasis during deployment were slightly older. A personal
      history or family history of stone disease was significant predictors of
      urolithiasis in this deployed population.

PMID- 19395004
TI  - Male genital representation in paleolithic art: erection and circumcision before
      history.
AB  - OBJECTIVES: To report on the likely existing evidence about the practice of
      circumcision in prehistory, or at least a culture of foreskin retraction, and
      also the meaning of erection in Paleolithic minds. The origin of the ritual of
      circumcision has been lost in time. Similarly, the primitive anthropologic
      meaning of erection is undefined. METHODS: We studied the archeologic and
      artistic evidence regarding human representations performed during the Upper
      Paleolithic period, 38,000 to 11,000 years BCE, in Europe, with a focus on
      genital male representations in portable and rock art. RESULTS: Drawings,
      engravings, and sculptures displaying humans are relatively scarce, and <100
      examples of male genitals are specifically represented. Some depict a circumcised
      penis and other represent urologic disorders such as phimosis, paraphimosis,
      discharge, priapism, or a scrotal mass. In addition, a small number of phalluses
      carved in horn, bone, or stone, with varying morphology, has survived to the
      present and also reveals a sustained cult for male erection and foreskin
      retraction not limited to a particular topographical territory. The very few
      noncoital human or humanoid figures with marked erection appear in a context of
      serious danger or death. Therefore, erection could be understood as a phenomenon
      related to the shamanic transit between life and death. CONCLUSIONS: The erection
      in Paleolithic art is explicitly represented in almost all the figures defined as
      unequivocally male that have survived to the present and in many objects of
      portable art. Circumcision and/or foreskin retraction of the penis are present in
      most of the works.

PMID- 19395005
TI  - Clinical and transvaginal sonographic evaluation of the prostate in transsexual
      women.
AB  - OBJECTIVES: To assess feasibility and diagnostic performance of prostate
      examination through transvaginal palpation and transvaginal ultrasound in
      transsexual women (TSW). METHODS: Fifty TSW who were at least 6 months'
      posttransition were recruited in a University Hospital. Speculum examination and
      digital vaginal examination were performed by a gynecologist. Transvaginal
      ultrasound of the prostate was performed by a radiologist. The information
      gathered included: ease of insertion of the speculum, vaginal length, palpability
      of the prostate, vaginal mobility and presence of scar tissue, ease of
      introduction of the ultrasound probe, ability to visualize prostate and seminal
      vesicles, echogenicity of the peripheral zone and the central gland, presence of
      calcifications and delineation of prostatic capsule, attitude toward gynecologic
      examinations, and anticipated and experienced painfulness of the different
      examinations. RESULTS: Speculum examination was possible in all but 1 patient and
      was easy in 78% of the patients. Median vaginal length was 7 cm. A regular
      digital vaginal examination was possible in 44% of the patients, the vagina was
      rather mobile and with limited scar tissue on average. In 48% of the patients,
      the prostate was palpable. In 94% of the patients, the prostate was visible on
      transvaginal ultrasound. Mean prostate volume was 14 mL, calcifications were
      present in 33%, and none had cysts. Capsule of the prostate was well delineated
      in 74% and seminal vesicles were visualized in 80%. All examinations were very
      well tolerated and nearly painless. CONCLUSIONS: Gynecologic examination and
      prostate assessment were acceptable to TSW. Transvaginal palpation of the
      prostate is of poor clinical value, yet transvaginal ultrasound allows for proper
      evaluation of the prostate status.

PMID- 19395006
TI  - Is warm temperature necessary to prevent urethral stricture in combined
      transurethral resection and vaporization of prostate?
AB  - OBJECTIVES: To compare the effect of warm and room temperature irrigation
      solution on the incidence of urethral stricture during combined transurethral
      resection and vaporization of the prostate (CTURVP). Urethral stricture after
      transurethral surgery of the prostate is a bothersome complication. Warm
      irrigation improves the blood flow and might decrease the incidence of urethral
      stricture compared with the use of room temperature irrigation, which decreases
      the blood flow in the urethral mucosa, resulting in ischemic injury. METHODS: The
      patients who underwent CTURVP were divided into those receiving only room
      temperature irrigation solution (group 1, 75 patients) or warm irrigation
      solution with a system maintaining the temperature of the ventral penile skin at
      about 36 degrees C continuously (group 2, 78 patients). At follow-up, 1, 3, and 6
      months later, the International Prostate Symptom Score and peak urine flow rate
      were evaluated. RESULTS: The temperature of the ventral penile skin was 20
      degrees C and 36 degrees C in groups 1 and 2, respectively. The rate of urethral
      stricture was 21.3% in group 1 and 6.3% in group 2 at the end of 6 months of
      follow-up (P = .002). CONCLUSIONS: The results of our study have shown that
      maintaining the temperature of the urethra with warm irrigation solution during
      CTURVP probably decreases the incidence of urethral stricture. The temperature in
      the urethra could be another important factor in stricture formation after
      CTURVP.

PMID- 19395007
TI  - Mutations in intron 8 and intron 9 of Wilms' tumor genes in members of family
      with ureteropelvic junction obstruction.
AB  - Ureteral obstruction with subsequent hydronephrosis is clinically common. Most
      cases are identified and diagnosed in the perinatal period. The diagnosis of
      ureteropelvic junction obstruction (UPJO) implies a functionally significant
      impairment of the urinary transportation from the renal pelvis to the ureter.
      Although most cases are probably congenital in origin, they can clinically remain
      hidden until much later in life. UPJO is usually considered an isolated event.
      Recently, we have evaluated a father and his 3 sons, all of whom had UPJO. This
      study reports a missense mutation of threonine 386, which was replaced with
      alanine in Wilms' tumor genes. We suggest that UPJO might not necessarily be
      sporadic and other family members might have a similar problem.

PMID- 19395008
TI  - Improved progression-free and overall survival in advanced ovarian cancer as a
      result of a change in surgical paradigm.
AB  - OBJECTIVE: To determine the impact on progression-free survival (PFS) and overall
      survival (OS) of a programmatic change in surgical approach to advanced
      epithelial ovarian cancer. METHODS: Two groups of patients with stage IIIC and IV
      ovarian, tubal, and peritoneal carcinoma were compared. Group 1, the control
      group, consisted of all 168 patients who underwent primary cytoreduction from
      1/96 to 12/99. Group 2, the study group, consisted of all 210 patients who
      underwent primary surgery from 1/01 to 12/04, during which time a more
      comprehensive debulking of upper abdominal disease was utilized. RESULTS: There
      were no differences between the groups in age, primary site of disease, surgical
      stage, tumor grade, American Society of Anesthesiologists class, preoperative
      serum CA-125 and platelet levels, percentage with or amount of ascites, size or
      location of largest tumor mass, or type of postoperative chemotherapy. Patients
      in Group 2 vs Group 1 more frequently had extensive upper abdominal procedure(s)
      (38% vs 0%, respectively; P<0.001) and cytoreduction to residual disease <1 cm
      (80% vs 46%, respectively; P<0.01). Five-year PFS and OS rates were significantly
      improved in Group 2. For Group 2 vs Group 1 patients, 5-year PFS rates were 31%
      vs 14%, respectively (hazard ratio, 0.757; 95% CI, 0.601-0.953; P=0.01]; and 5
      year OS rates were 47% vs 35%, respectively (HR, 0.764; 95% CI, 0.592-0.987;
      P=0.03]. CONCLUSION: The incorporation of extensive upper abdominal procedures
      resulted in increased optimal cytoreduction rates and significantly improved PFS
      and OS. A paradigm shift toward more complete primary cytoreduction can improve
      survival for patients with advanced ovarian, tubal, and peritoneal carcinomas.

PMID- 19395009
TI  - Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs
      in flies.
AB  - Piwi-interacting RNAs (piRNAs) silence transposons in animal germ cells. piRNAs
      are thought to derive from long transcripts spanning transposon-rich genomic loci
      and to direct an autoamplification loop in which an antisense piRNA, bound to
      Aubergine or Piwi protein, triggers production of a sense piRNA bound to the PIWI
      protein Argonaute3 (Ago3). In turn, the new piRNA is envisioned to produce a
      second antisense piRNA. Here, we describe strong loss-of-function mutations in
      ago3, allowing a direct genetic test of this model. We find that Ago3 acts to
      amplify piRNA pools and to enforce on them an antisense bias, increasing the
      number of piRNAs that can act to silence transposons. We also detect a second,
      Ago3-independent piRNA pathway centered on Piwi. Transposons targeted by this
      second pathway often reside in the flamenco locus, which is expressed in somatic
      ovarian follicle cells, suggesting a role for piRNAs beyond the germline.

PMID- 19395010
TI  - Specialized piRNA pathways act in germline and somatic tissues of the Drosophila
      ovary.
AB  - In Drosophila gonads, Piwi proteins and associated piRNAs collaborate with
      additional factors to form a small RNA-based immune system that silences mobile
      elements. Here, we analyzed nine Drosophila piRNA pathway mutants for their
      impacts on both small RNA populations and the subcellular localization patterns
      of Piwi proteins. We find that distinct piRNA pathways with differing components
      function in ovarian germ and somatic cells. In the soma, Piwi acts singularly
      with the conserved flamenco piRNA cluster to enforce silencing of retroviral
      elements that may propagate by infecting neighboring germ cells. In the germline,
      silencing programs encoded within piRNA clusters are optimized via a slicer
      dependent amplification loop to suppress a broad spectrum of elements. The
      classes of transposons targeted by germline and somatic piRNA clusters, though
      not the precise elements, are conserved among Drosophilids, demonstrating that
      the architecture of piRNA clusters has coevolved with the transposons that they
      are tasked to control.

PMID- 19395012
TI  - The adsorption properties of short chain alcohols and Triton X-100 mixtures at
      the water-air interface.
AB  - The adsorption behaviour at the water-air interface of aqueous solutions of
      Triton X-100 and methanol (ethanol) mixtures at constant Triton X-100 (TX-100)
      concentration equal to 10(-7), 10(-6), 10(-5), 10(-4), 6x10(-4) and 10(-3)M,
      respectively, in a wide range of alcohol concentration was investigated by
      surface tension measurements of solutions. The obtained values of the surface
      tension of aqueous solutions of "pure" methanol and ethanol and their mixtures
      with TX-100, as well as the values of propanol solutions and their mixtures with
      TX-100 as a function of alcohol concentration taken from the literature were
      compared with those calculated from the Szyszkowski, Connors and Fainerman and
      Miller equations. On the basis of this comparison it was stated that these
      equations can be useful for description of the solution surface tension in the
      wide range of alcohol concentration, but only at the concentrations of Triton X
      100 corresponding to its unsaturated layer in the absence of alcohol. It was also
      stated that the Connors equation is more adequate for concentrated aqueous
      organic solutions. The measured values of the surface tension were used in the
      Gibbs equation to determine the surface excess concentration of Triton X-100 and
      alcohol. Next, on the basis of Gibbs adsorption isotherms those of Guggenheim and
      Adam and real adsorption isotherms were established. From the obtained adsorption
      isotherms it results that alcohol influences the shape of TX-100 isotherms in the
      whole range of alcohol and TX-100 concentration, but TX-100 influences the
      alcohol isotherms only at TX-100 concentration at which the saturated monolayer
      at the solution-air interface is formed in the absence of alcohol. This
      conclusion was confirmed by analysis of the composition of the surface layer in
      comparison to the composition of the bulk phase in the equilibrium state.

PMID- 19395011
TI  - A collaboration of aquaporins handles water transport in relation to the estrous
      cycle in the bitch uterus.
AB  - Fluid movement through uterine cell membranes is crucial, as it can modulate the
      tissue imbibition pattern in the different phases of the estrous cycle. To gain
      insight into the mechanisms underlying steroid-controlled water handling, the
      presence and distribution of aquaporins (AQPs), integral membrane channel
      proteins permitting rapid passive water movement, was explored in bitch uterine
      tissues. Immunohistochemistry and Western immunoblot analysis were used to study
      the presence of AQP1, AQP2, and AQP5 in the layers of the bitch uterine wall
      during the different estrous phases. Presence of endothelial nitric oxide
      generating enzyme NO synthase (NOS3) was also investigated, as it is known that
      the vasodilator NOS3 might be involved in the development of uterine edema. The
      results demonstrated the following: (1) AQP1, AQP2, and AQP5 were present in the
      uterus of cycling bitches. (2) AQP1 was localized within uterine mesometrial,
      myometrial, and endometrial blood vessels and in the circular and longitudinal
      layers of myometrium. AQP1 localization and expression were unaffected by the
      estrous cycle. (3) The estrogenic milieu was probably at the basis of AQP2
      expression in the glandular and luminal epithelium of the endometrium. (4) AQP5
      water channels were present in the apical plasma membrane of uterine epithelial
      cells in coincidence with plasma progesterone increase. (5) NOS3 was localized in
      the myometrial and epithelial tissues as well as in blood vessels indicating a
      contribution of this vasoactive peptide to the uterine imbibition processes.
      Thus, we can hypothesize that a functional and distinctive collaboration exists
      among diverse AQPs in water handling during the different functional uterine
      phases.

PMID- 19395013
TI  - Thermal control of electroosmotic flow in a microchannel through temperature
      dependent properties.
AB  - A numerical investigation is conducted on the electroosmotic flow and associated
      heat transfer in a two-dimensional microchannel. The objective of this study is
      to explore a new conceptual idea that is control of an electroosmotic flow by
      using a thermal field effect through the temperature-dependent physical
      properties. Two exemplary problems are examined: a flow in a microchannel with a
      constant vertical temperature difference between two horizontal walls and a flow
      in a microchannel with the wall temperatures varying horizontally in a sinusoidal
      manner. The results of numerical computations showed that a proper control of
      thermal field may be a viable means to manipulate various non-plug-like flow
      patterns. A constant vertical temperature difference across the channel produces
      a shear flow. The horizontally-varying thermal condition results in spatial
      variation of physical properties to generate fluctuating flow patterns. The
      temperature variation at the wall with alternating vertical temperature gradient
      induces a wavy flow.

PMID- 19395014
TI  - Mesoporous titanosilicates with high loading of titanium synthesized in mild
      acidic buffer solution.
AB  - Mesoporous titanosilicates with high titanium content were synthesized under mild
      acidic conditions (pH=4.4, HAc-NaAc buffer solution) by co-condensation of
      acetylacetone-modified titanium isopropoxide (Ti(OBu(n))(3) (acac)) and mixture
      of sodium silicate with tetramethoxysilane (TMOS) or tetraethoxysilane (TEOS) or
      tetrakis(2-hydroxyethyl)orthosilicate (EGMS), using block copolymer Pluronic P123
      as template. The combined results of XRD, N(2) sorption and TEM show that the
      highly regular structure of the mesoporous titanosilicates can still be obtained
      when Ti/Si molar ratio in the final product is as high as 0.059. The results of
      UV-vis diffuse reflectance spectra and UV resonance Raman spectra show that the
      framework titanium species are predominant in the mesoporous titanosilicates when
      Ti/Si molar ratio in the final product is less than 0.042. The mixture of sodium
      silicate and EGMS was proved to be the best silicon source for the synthesis of
      titanosilicates with ordered mesostructure and high titanium content. The
      efficiency of this synthetic method may be attributed to the mild acidic medium
      as well as the modified hydrolysis-condensation rate and hydrophility of the
      precursors.

PMID- 19395015
TI  - Biosensing by optical waveguide spectroscopy based on localized surface plasmon
      resonance of gold nanoparticles used as a probe or as a label.
AB  - The application of localized surface plasmon resonance (LSPR) of gold
      nanoparticles for the detection of biotin-streptavidin binding, as a typical
      biological reaction, was investigated by using optical waveguide spectroscopy,
      and two different modes for the use of gold nanoparticles, one as a probe and the
      other as a label were compared with each other. The combination with optical
      waveguide spectroscopy was found to bring about a high sensitivity for the
      biomolecular detection system using LSPR of gold nanoparticles in both modes. In
      particular, the mode using gold nanoparticles as a label was demonstrated to be
      of advantage to devising proper procedures for using nanoparticles and evaluating
      actual response relevant to the phenomenon concerned, and thus to sensitive
      detection.

PMID- 19395016
TI  - Bis-GMA co-polymerizations: influence on conversion, flexural properties,
      fracture toughness and susceptibility to ethanol degradation of experimental
      composites.
AB  - OBJECTIVES: The aim of this study was to evaluate the influence of monomer
      content on fracture toughness (K(Ic)) before and after ethanol solution storage,
      flexural properties and degree of conversion (DC) of bisphenol A glycidyl
      methacrylate (Bis-GMA) co-polymers. METHODS: Five formulations were tested,
      containing Bis-GMA (B) combined with TEGDMA (T), UDMA (U) or Bis-EMA (E), as
      follows (in mol%): 30B:70T; 30B:35T:35U; 30B:70U; 30B:35T:35E; 30B:70E. Bimodal
      filler was introduced at 80 wt%. Single-edge notched beams for fracture toughness
      (FT, 25 mm x 5 mm x 2.5 mm, a/w=0.5, n=20) and 10 mm x 2 mm x 1 mm beams for
      flexural strength (FS) and modulus (FM) determination (10 mm x 2 mm x 1 mm, n=10)
      were built and then stored in distilled water for 24 h at 37 degrees C. All FS/FM
      beams and half of the FT specimens were immediately submitted to three-point
      bending test. The remaining FT specimens were stored in a 75%ethanol/25%water
      (v/v) solution for 3 months prior to testing. DC was determined with FT-Raman
      spectroscopy in fragments of both FT and FS/FM specimens at 24 h. Data were
      submitted to one-way ANOVA/Tukey test (alpha=5%). RESULTS: The 30B:70T composite
      presented the highest K(Ic) value (in MPa m(1/2)) at 24 h (1.3+/-0.4),
      statistically similar to 30B:35T:35U and 30B:70U, while 30B:70E presented the
      lowest value (0.5+/-0.1). After ethanol storage, reductions in K(Ic) ranged from
      33 to 72%. The 30B:70E material presented the lowest reduction in FT and 30B:70U,
      the highest. DC was similar among groups (69-73%), except for 30B:70U (52+/-4%,
      p<0.001). 30B:70U and 30B:35T:35U presented the highest FS (125+/-21 and 122+/-14
      MPa, respectively), statistically different from 30B:70T or 30B:70E (92+/-20 and
      94+/-16 MPa, respectively). Composites containing UDMA or Bis-EMA associated with
      Bis-GMA presented similar FM, statistically lower than 30B:35T:35U. SIGNIFICANCE:
      Composites formulated with Bis-GMA:TEGDMA:UDMA presented the best compromise
      between conversion and mechanical properties.

PMID- 19395017
TI  - The influence of SiO2 and SiO2-TiO2 intermediate coatings on bond strength of
      titanium and Ti6Al4V alloy to dental porcelain.
AB  - OBJECTIVES: The purpose of this study was to evaluate the bond strength of
      commercially pure CPTi and Ti6Al4V alloy with SiO2 and SiO2-TiO2 intermediate
      coatings to Triceram low-fusing dental porcelain. METHODS: The multilayered
      systems were characterized from the standpoint of microstructure analysis (SEM),
      the mode of failure, the nature of bonding and the influence of intermediate
      coatings on the improvement of bond strength. The SiO2 and SiO2-TiO2 intermediate
      coatings were applied on the substrate materials by the sol-gel dipping
      technique. The metal-ceramic bond strength was investigated according to ISO 9693
      standards using the three-point flexure bond test. RESULTS: Statistically
      significant higher bond strength of the metal-porcelain for Ti6A14V alloy (28.24
      MPa), Ti6Al4V/SiO2 (32.17 MPa) and Ti6Al4V/SiO2-TiO2 (36.09 MPa) was noted in
      comparison to CPTi (23.04 MPa), CPTi/SiO2 (27.98 MPa) and CPTi/SiO2-TiO2 (28.84
      MPa), respectively. The nature of metal-intermediate coating-porcelain bonding
      was both mechanical and chemical. The failure in all systems was cohesive and
      adhesive, mainly adhesive. SIGNIFICANCE: The application of SiO2 and SiO2-TiO2
      intermediate coatings, produced by the sol-gel method, to both CPTi and Ti6Al4V
      alloy significantly improves the bond strength of metal-porcelain systems in
      comparison to the metal substrate only after sandblasting, and may have clinical
      use.

PMID- 19395018
TI  - Where the education system and women's bodies collide: The social and health
      impact of girls' experiences of menstruation and schooling in Tanzania.
AB  - The global development community has focused in recent decades on closing the
      gender gap in education, but has given insufficient attention to the specific
      needs of pre- and post-pubescent girls as they transition to young womanhood
      within the educational institution. This study explored the social context of
      girls' experiences of menses and schooling in northern Tanzania, with data
      collection focused on capturing girls' voiced concerns and recommendations.
      Results indicated that pubescent girls are confronted with numerous challenges to
      managing menses within the school environment. Many are transitioning through
      puberty without adequate guidance on puberty and menses management, and pursuing
      education in environments that lack adequate facilities, supplies, and gender
      sensitivity. Girls have pragmatic and realistic recommendations for how to
      improve school environments, ideas that should be incorporated as effective
      methods for improving girls' academic experiences and their healthy transitions
      to womanhood.

PMID- 19395019
TI  - Cell-controlled and spatially arrayed gene delivery from fibrin hydrogels.
AB  - We investigated fibrin-mediated gene transfer by embedding pDNA within the
      hydrogel during polymerization and using two modes of gene transfection with
      cells placed either on the surface (2D transfection) or within the hydrogel (3D
      transfection). Using this model, we found that cell transfection depended
      strongly on the local cell-pDNA microenvironment as defined by the 2D vs. 3D
      context, target cell type and density, as well as fibrinogen and pDNA
      concentrations. When cells were embedded within the fibrin matrix lipofectamine
      induced cell death decreased significantly, especially at low target cell
      density. Addition of fibrinolytic inhibitors decreased gene transfer in a dose
      dependent manner, suggesting that fibrin degradation may be necessary for
      efficient gene transfer. We also provided proof-of-concept that fibrin-mediated
      gene transfer can be used for spatially localized gene delivery, which is
      required in cell-transfection microarrays. When lipoplex-containing hydrogels
      were spotted in an array format gene transfer was strictly confined to pDNA
      containing fibrin spots with no cross-contamination between neighboring sites.
      Collectively, our data suggest that fibrin may be used as a biomaterial to
      deliver genes in an efficient, cell-controlled and spatially localized manner for
      potential applications in vitro or in vivo.

PMID- 19395020
TI  - Dual chemotherapy and photodynamic therapy in an HT-29 human colon cancer
      xenograft model using SN-38-loaded chlorin-core star block copolymer micelles.
AB  - Chlorin-core star-shaped block copolymer (CSBC) may self-assemble to form
      micelles, which act as nanosized photosensitizing agents for photodynamic therapy
      (PDT) and further encapsulate hydrophobic drugs. This functionalized micellar
      delivery system is a potential dual carrier for the synergistic combination of
      photodynamic therapy and chemotherapy for the treatment of cancer. In this study,
      SN-38 encapsulated CSBC micelles were successfully prepared using a
      lyophilization-hydration method. Our results show that the prolonged plasma
      residence time of SN-38/CSBC micelles as compared with free CPT-11 permit
      increased tumor accumulation and consequently, improved antitumor activity. The
      combined effects of SN-38/CSBC micelles with PDT were evaluated in an HT-29 human
      colon cancer xenograft model. Interesting, SN-38/CSBC-mediated PDT
      synergistically inhibited tumor growth, resulting in up to 60% complete
      regression of well-established tumors after 3 treatments. These treatments also
      decreased the microvessel density (MVD) and cell proliferation within the
      subcutaneous tumors. Therefore, this SN-38/CBSC delivery system has the potential
      to offer dual therapies for the synergistic combination of PDT and chemotherapy
      for the treatment of cancer.

PMID- 19395021
TI  - The antimicrobial efficacy of sustained release silver-carbene complex-loaded L
      tyrosine polyphosphate nanoparticles: characterization, in vitro and in vivo
      studies.
AB  - The pressing need to treat multi-drug resistant bacteria in the chronically
      infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized
      antimicrobials. We have synthesized a silver-carbene complex (SCC10) active
      against a variety of bacterial strains associated with CF and chronic lung
      infections. Our studies have demonstrated that SCC10-loaded into L-tyrosine
      polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity
      in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa.
      Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial
      over the course of several days translating into efficacious results in vivo with
      only two administered doses over a 72 h period.

PMID- 19395022
TI  - Mechanisms regulating increased production of osteoprotegerin by osteoblasts
      cultured on microstructured titanium surfaces.
AB  - Osteoblasts grown on microstructured Ti surfaces enhance osteointegration by
      producing local factors that regulate bone formation as well as bone remodeling,
      including the RANK ligand decoy receptor osteoprotegerin (OPG). The objective of
      this study was to explore the mechanism by which surface microstructure and
      surface energy mediate their stimulatory effects on OPG expression. Titanium
      disks were manufactured to present different surface morphologies: a smooth
      pretreatment surface (PT, Ra<0.2microm), microstructured sandblasted/acid etched
      surface (SLA, Ra=3-4microm), and a microstructured Ti plasma-sprayed surface
      (TPS, Ra=4microm). Human osteoblast-like MG63 cells were cultured on these
      substrates and the regulation of OPG production by TGF-beta1, PKC, and
      alpha2beta1 integrin signaling determined. Osteoblasts produced increased amounts
      of OPG as well as active and latent TGF-beta1 and had increased PKC activity when
      grown on SLA and TPS. Exogenous TGF-beta1 increased OPG production in a dose
      dependent manner on all surfaces, and this was prevented by adding blocking
      antibody to the TGF-beta type II receptor or by reducing TGF-beta1 binding to the
      receptor by adding exogenous soluble type II receptor. The PKC inhibitor
      chelerythrine inhibited the production of OPG in a dose-dependent manner, but
      only in cultures on SLA and TPS. shRNA knockdown of alpha2 or a double knockdown
      of alpha2beta1 also reduced OPG, as well as production of TGF-beta1. These
      results indicate that substrate-dependent OPG production is regulated by TGF
      beta1, PKC, and alpha2beta1 and suggest a mechanism by which alpha2beta1
      signaling increases PKC, resulting in TGF-beta1 production and TGF-beta1 then
      acts on its receptor to increase transcription of OPG.

PMID- 19395023
TI  - Extraction techniques for the decellularization of tissue engineered articular
      cartilage constructs.
AB  - Several prior studies have been performed to determine the feasibility of tissue
      decellularization to create a non-immunogenic xenogenic tissue replacement for
      bladder, vasculature, heart valves, knee meniscus, temporomandibular joint disc,
      ligament, and tendon. However, limited work has been performed with articular
      cartilage, and no studies have examined the decellularization of tissue
      engineered constructs. The objective of this study was to assess the effects of
      different decellularization treatments on articular cartilage constructs,
      engineered using a scaffoldless approach, after 4wks of culture, using a two
      phased approach. In the first phase, five different treatments were examined: 1)
      1% SDS, 2) 2% SDS, 3) 2% Tributyl Phosphate, 4) 2% Triton X-100, and 5) Hypotonic
      followed by hypertonic solution. These treatments were applied for either 1h or
      8h, followed by a 2h wash in PBS. Following this wash, the constructs were
      assessed histologically, biochemically for cellularity, GAG, and collagen
      content, and biomechanically for compressive and tensile properties. In phase II,
      the best treatment from phase I was applied for 1, 2, 4, 6, or 8h in order to
      optimize the application time. Treatment with 2% SDS for 1h or 2h significantly
      reduced the DNA content of the tissue, while maintaining the biochemical and
      biomechanical properties. On the other hand, 2% SDS for 6h or 8h resulted in
      complete histological decellularization, with complete elimination of cell nuclei
      on histological staining, although GAG content and compressive properties were
      significantly decreased. Overall, 2% SDS, for 1 or 2h, appeared to be the most
      effective agent for cartilage decellularization, as it resulted in
      decellularization while maintaining the functional properties. The results of
      this study are exciting as they indicate the feasibility of creating engineered
      cartilage that may be non-immunogenic as a replacement tissue.

PMID- 19395024
TI  - Cystinosis of the brain and spinal cord with associated vasculopathy.
AB  - Cystinosis is an autosomal recessive lysosomal storage disease that results in
      renal failure. CNS manifestations are rare. We report a 29-year man who presented
      with a cervical myelopathy due to cystinosis. Biopsy of the brain lesions
      demonstrated cystine crystal deposition and an intense perivascular with
      inflammatory vasculopathic changes. Symptomatic improvement attended the use of
      higher doses of cysteamine and corticosteroid therapy. Cystinosis of the nervous
      system may present as spinal cord disease and be associated with a CNS
      vasculopathy/vasculitis. As more patients with cystinosis experience long term
      survival, there will likely be an increased frequency of CNS disease.

PMID- 19395025
TI  - BAFF and APRIL expression in B-cell chronic lymphocytic leukemia: correlation
      with biological and clinical features.
AB  - B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are
      involved in normal B cell survival and differentiation. We analyzed BAFF and
      APRIL plasma levels in patients with B-cell chronic lymphocytic leukemia (B-CLL).
      We also tested intracellular BAFF and APRIL expression in B-CLL and evaluated
      their prognostic relevance. The percentage of leukemic B cells with intracellular
      APRIL or BAFF expression correlated significantly with adverse prognostic factors
      such as ZAP-70 and CD38. Moreover, we found a close relationship between LPL
      protein expression or LPL/ADAM29 MFI ratio and proportion of B-CLL cells with
      intracellular BAFF or APRIL expression. Furthermore, patients with a low
      percentage of leukemic cells with intracellular BAFF or APRIL expression had a
      significantly longer overall survival than those with a high proportion of APRIL
      or BAFF positive leukemic cells.

PMID- 19395026
TI  - OH-2, a hyperdiploid myeloma cell line without an IGH translocation, has a
      complex translocation juxtaposing MYC near MAFB and the IGK locus.
AB  - Multiple myeloma can be classified into hyperdiploid (HRD) (with 48-74
      chromosomes) and non-hyperdiploid tumors (usually with immunoglobulin heavy chain
      translocations). The OH-2 human myeloma cell line (HMCL) retains the same HRD
      genotype as the primary tumor, with extra copies of chromosomes 3, 7, 15, 19, and
      21. Both OH-2 and primary cells have a complex secondary translocation in which
      the IGK 3' enhancer is inserted between MYC and MAFB, resulting in dysregulation
      of both oncogenes. OH-2 provides a unique example of an HMCL and the
      corresponding primary tumor that are shown to share the same HRD genotype.

PMID- 19395027
TI  - Correlation between trough imatinib plasma concentration and clinical response in
      chronic myeloid leukemia.

PMID- 19395028
TI  - Absence of FLT3 and JAK2 (V617F) mutations in Langerhans cell histiocytosis.

PMID- 19395029
TI  - [CT and MR brain imaging following hemispherotomy].
AB  - PURPOSE: The aim of the study was to define the usual and pathological
      modifications arising in the brain following hemispherotomy for intractable
      epilepsy in children. METHODS: Preoperative MRI and postoperative imaging scans
      (CT in the first week, MRI at 3 months and 1 year after surgery) were reviewed in
      a series of 52 patients, average age 8 years and 7 months, with intractable
      epilepsy due to dysplasia, Rasmussen's encephalitis, ischemic lesions and/or
      Sturge-Weber disease. The posterior fossa, brain parenchyma, ventricles and
      subdural space were also analyzed. RESULTS: Hemispheric scarring was a typical
      finding on CT and MRI as a consequence of the surgical procedure. Also frequently
      seen were small subdural effusions, bleeding along the surgical scar on early CT,
      and chronic subdural effusions with no mass effect on mid-term and late MRI
      scans. Other features - such as large subdural effusions that required external
      shunts and hydrocephalus - were rare, but severe, and considered to be
      postoperative complications. In contrast to the complications associated with
      other surgical techniques such as hemispherectomy, infection, extensive edema or
      hemosiderosis were never found in our series. CONCLUSION: Hemispherotomy is a
      surgical technique performed to treat intractable epilepsy. Our findings will
      help to identify the typical morphology of postsurgical scars, and to
      differentiate the usual features and complications seen in the postoperative
      period on CT and MRI brain scans.

PMID- 19395031
TI  - Re: Genitofemoral nerve injury after laparoscopic varicocelectomy in adolescents.
      O. J. Muensterer. J Urol 2008; 180: 2155-2158.

PMID- 19395032
TI  - Extending the environmental risk assessment for oseltamivir (Tamiflu) under
      pandemic use conditions to the coastal marine compartment.
AB  - In case of an avian-influenza-derived human flu pandemic, an inordinately high
      use of medicines over several weeks is predicted, in particular for the
      recommended influenza antiviral oseltamivir (Tamiflu). While the risk of
      oseltamivir to sewage works and freshwater bodies has already been assessed, the
      fact that a large percentage of the human population worldwide lives relatively
      close to the sea raises concern for its environmental compatibility in coastal
      marine waters. The potential risk of high oseltamivir use to the marine
      compartment is assessed in this publication, based on the 2003 European Community
      Technical Guidance Document (TGD) for risk assessment. Subchronic embryo-larval
      ecotoxicity tests with three marine invertebrates (Pomatoceros triqueter,
      Annelida; Mytilus edulis, Mollusca; Paracentrotus lividus, Echinodermata) and
      chronic growth inhibition tests with two different groups of marine microalgae
      (Isochrysis galbana, Haptophyta; Skeletonema costatum, Heterokontophyta) were
      performed with the active substance oseltamivir carboxylic acid to derive a
      dependable marine predicted no-effect concentration (PNEC). This was compared to
      a predicted environmental concentration (PEC) for oseltamivir in coastal waters,
      based on the worst-case freshwater PEC. The PEC/PNEC risk characterisation ratio
      for the marine compartment is well below 1, which in the terminology of the TGD
      signifies no immediate concern. Further, while oseltamivir may be persistent (P),
      it is not bioaccumulative (B) nor highly ecotoxic (T) and therefore not a PBT
      substance. In conclusion, even a high pandemic use of oseltamivir would not lead
      to a significant risk for the marine compartment, in confirmation of the risk
      assessment for sewage works and freshwaters.

PMID- 19395033
TI  - Influence of environment on insulin sensitivity.
AB  - Genetic and environmental factors influence insulin sensitivity (IS) during one's
      lifetime. Actually, uterine environment may affect IS at birth and later in life.
      In particular, various exogenous toxic substances, coupled to a genetic
      predisposition, may remarkably influence the regulation of the hypothalamus
      hypophysis-adrenal gland axis, and the production or the activity of insulin,
      cerebral incretins, pro-inflammatory cytokines, and placental hormones. Owing to
      this reaction against environmental injuries, fetal growth and endocrine system
      development may be impaired, leading to low or large birth weight, or
      prematurity. Reduced growth in early life has been related to insulin resistance,
      which can be silent for years and evident in predisposed adults. The incidence of
      type 2 diabetes mellitus and obesity associated with sedentary lifestyle patterns
      and inadequate dieting behaviors in children and adolescents has rapidly
      increased during the last decade. Recent evidences suggest that the Pro12Ala
      polymorphism of the peroxisome proliferator-activated receptor- (PPAR-) gene and
      the angiotensin converting enzyme (ACE) I/D gene polymorphism combined with
      environmental factors, such as phthalates interfering with the post receptorial
      action of insulin, alter insulin-sensible tissues. Therefore, IS, deriving from a
      complex interaction between genotype and environment, may change during life and
      depends on previous metabolic control, which is a sort of metabolicmemory. The
      goal for the future is preventing the complications associated with impaired IS
      through the control of exogenous factors and the use of drugs selectively
      effective on its pathogenesis.

PMID- 19395034
TI  - Correlation between spectral domain optical coherence tomography findings and
      fluorescein angiography patterns in diabetic macular edema.
AB  - OBJECTIVE: To study the relationship between spectral domain optical coherence
      tomography (SD-OCT) findings and fluorescein angiography (FA) patterns in
      patients with diabetic macular edema (DME). DESIGN: Retrospective, observational,
      cross-sectional study. PARTICIPANTS: We included 59 eyes from 59 patients with
      DME that had SD-OCT/scanning laser ophthalmoscope (SLO) and FA performed on the
      same day. Eyes with macular edema owing to other ocular diseases were excluded.
      METHODS: The relationship between SD-OCT and FA findings was evaluated by
      superimposing and aligning the SLO images onto the FA photos. The SLO image of
      the OPKO/OTI Spectral OCT/SLO (OPKO-OTI, Miami, FL) corresponds with the exact
      origin and orientation of the SD-OCT scan, which was then correlated with the FA
      image. Foveal and extrafoveal regions were studied separately. Leakage on FA and
      pathologic changes on OCT were graded by using standard photographs. Pathologic
      changes studied in the OCT images included edema and cystic spaces in the inner
      and outer retina, loss of retinal layers, and foveal cysts. MAIN OUTCOME
      MEASURES: Correlation between SD-OCT changes and corresponding FA patterns.
      RESULTS: The outer retina was the predominant location of fluid in DME. The
      severity of the outer retinal edema on OCT was positively correlated with the
      severity of leakage on FA (r = 0.735; P<0.001). Cystic changes in the inner and
      outer retina were also correlated with the severity of fluorescein leakage (r =
      0.507 and P<0.001; r = 0.561 and P<0.001, respectively). Loss of inner retinal
      layers on OCT was highly correlated with capillary nonperfusion on FA (r = 0.953;
      P<0.001). Large foveal cysts on SD-OCT corresponded to cystoid leakage patterns
      on FA. CONCLUSIONS: Pathologic changes on SD-OCT correlated well with FA
      findings. Loss of inner retinal layers was specifically correlated with capillary
      nonperfusion and severe ischemia. Judgment of whether management of DME based on
      fine retinal structural changes influences clinical outcomes must be reserved
      pending further investigation with prospective trials. FINANCIAL DISCLOSURE(S):
      Proprietary or commercial disclosure may be found after the references.

PMID- 19395035
TI  - Femtosecond laser arcuate keratotomy for the correction of high astigmatism after
      keratoplasty.
AB  - PURPOSE: To determine the feasibility and initial outcomes of using a femtosecond
      laser to perform arcuate keratotomies to correct high post-keratoplasty
      astigmatism. DESIGN: Prospective noncomparative interventional case series.
      PARTICIPANTS: Twelve eyes of 12 consecutive patients (mean age 44.9+/-9.5 years)
      who presented with a high degree of astigmatism, noncorrectable with spectacles
      or contact lenses (10 post-penetrating keratoplasty, 2 post-deep lamellar
      keratoplasty), and were candidates for relaxing incisional corneal surgery.
      METHODS: The Femtec (20/10 Perfect Vision, GmbH, Heidelberg, Germany) femtosecond
      laser performed paired 90-degree angled arcuate incisions on the graft button.
      The incision sites and depths were programmed at 1.00 mm inside the graft edge
      and at 90% of the corresponding local graft thickness, whereas the angular
      lengths of the cuts were determined by analyzing the locations and extents of the
      steepest meridians in the topographic map. MAIN OUTCOME MEASURES: Changes in
      uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
      mean subjective and topographically determined astigmatism; imaging of incisions
      by anterior segment optical coherence tomography (AS-OCT); and wound healing by
      in vivo confocal microscopy (IVCM). RESULTS: Postoperative follow-up extended to
      6 months. Mean uncorrected logarithm of the minimum angle of resolution (logMAR)
      BSCVA and UCVA improved from preoperative values of 0.25+/-0.16 and 1.05+/-0.18
      to 6-month values of 0.11+/-0.12 (standard deviation) and 0.55+/-0.34,
      respectively (P<0.05). Mean subjective astigmatism was 7.16+/-3.07 diopters (D)
      preoperatively and 2.23+/-1.55 D at 1 month after surgery (P = 0.002) and
      remained stable to the end of follow-up. Anterior segment optical coherence
      tomography image analysis showed that the depth and location of the incisions
      were consistent with the preoperative surgical plan. In vivo confocal microscopy
      showed mild edema and keratocyte activation along the incision edges, together
      with initial epithelial ingrowth inside the wound, followed by subsequent
      moderate fibrotic scarring. CONCLUSIONS: Arcuate keratotomies performed with the
      femtosecond laser were effective in reducing post-keratoplasty astigmatism. Laser
      generated incisions within the graft button presented precise geometry and
      reliable depth of incision, with a wound healing pattern characterized by
      epithelial ingrowth and mild fibrosis. FINANCIAL DISCLOSURE(S): The author(s)
      have no proprietary or commercial interest in any materials discussed in this
      article.

PMID- 19395036
TI  - Recipient risk factors for graft failure in the cornea donor study.
AB  - PURPOSE: To identify recipient factors that may be related to risk of corneal
      graft failure. DESIGN: Multicenter, prospective, double-masked, controlled
      clinical trial. PARTICIPANTS: One thousand ninety subjects undergoing corneal
      transplantation for a moderate-risk condition (principally Fuchs' dystrophy or
      pseudophakic corneal edema). METHODS: Donor corneas were assigned using a random
      approach without respect to recipient factors, and surgeons were masked to
      information about the donor cornea, including donor age. Surgery and
      postoperative care were performed according to the surgeons' usual routines, and
      subjects were followed up for 5 years. Baseline factors were evaluated for their
      association with graft failure. MAIN OUTCOME MEASURES: Graft failure, defined as
      a regraft or a cloudy cornea that was sufficiently opaque to compromise vision
      for a minimum of 3 consecutive months. RESULTS: Preoperative diagnosis of
      pseudophakic or aphakic corneal edema increased graft failure risk approximately
      4-fold compared with Fuchs' dystrophy (27% vs. 7%). Prior glaucoma surgery with
      preoperative glaucoma medication use substantially increased the graft failure
      rate. Factors not strongly associated with graft failure included age, gender,
      diabetes, smoking, and graft size. CONCLUSIONS: The risk of graft failure is
      significantly increased in eyes with pseudophakic or aphakic corneal edema
      compared with Fuchs' dystrophy, independent of lens status, and in eyes with a
      history of glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 19395037
TI  - Identifying preperimetric functional loss in glaucoma: a blue-on-yellow
      multifocal visual evoked potentials study.
AB  - PURPOSE: To determine the ability of blue-on-yellow multifocal visual evoked
      potentials (BonY mfVEP) to identify functional loss in preperimetric glaucoma.
      DESIGN: Prospective case series. PARTICIPANTS: Thirty patients with glaucomatous
      optic discs and normal standard visual fields. METHODS: All patients underwent
      BonY mfVEP, dilated optic disc stereophotography, and optical coherence
      tomography (Fast RNFL protocol). Optic disc photographs were assessed by 2
      independent examiners in a masked fashion. MAIN OUTCOME MEASURES: The mfVEP
      amplitude asymmetry and latency values were analyzed and compared topographically
      with findings of disc assessment. Average retinal nerve fiber layer (RNFL)
      thickness, RNFL asymmetry, and sectors with RNFL thinning were compared between
      patients with and without mfVEP defects. RESULTS: Fourteen (46.7%) patients
      demonstrated significant abnormality on amplitude asymmetry deviation plots of
      BonY mfVEP. In all 14 cases, the defect was monocular and corresponded to the eye
      with the worse disc. In 13 of 14 patients, the defect also corresponded to the
      location of the worst affected rim. Average RNFL thickness of eyes with mfVEP
      defects was 81.2+/-9.9 microm, significantly lower than that of patients without
      defects (90+/-10.5 microm; P = 0.035). Mean asymmetry of RNFL (better minus worse
      eye) also was significantly higher for patients with mfVEP defects compared with
      those without such defects (9.0+/-6.4 microm vs. 3.0+/-7 microm; P = 0.03).
      Average latency of both eyes of glaucomatous patients was delayed compared with
      that of controls, with no difference in latency between worse and better eyes of
      glaucoma patients. There was no association of latency delay with either the
      location of disc changes or mfVEP amplitude defects. CONCLUSIONS: Amplitude
      asymmetry of the BonY mfVEP seems to be a promising tool to identify functional
      loss in preperimetric glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or
      commercial disclosure may be found after the references.

PMID- 19395038
TI  - Antibiotic susceptibility of conjunctival bacterial isolates from refractive
      surgery patients.
AB  - PURPOSE: To determine the in vitro antibiotic susceptibility patterns of
      conjunctival bacterial flora isolated before surgery from patients undergoing
      refractive surgery. DESIGN: In vitro laboratory investigation. PARTICIPANTS: One
      hundred five eyes from 105 patients scheduled for refractive surgery at
      Balgensesang Ophthalmology Clinic between September 2005 and January 2006 were
      studied. Among 105 patients, 71 (67.6%) underwent LASIK using a femtosecond
      laser, 24 (22.9%) underwent LASIK using an automated microkeratome, 8 (7.6%)
      underwent LASEK, and 2 (1.9%) patients underwent phakic intraocular lens
      implantation. METHODS: Preoperative conjunctival swab samples were inoculated
      directly in culture media at the bedside before topical anesthetic or antibiotic
      application. Blood agar, chocolate agar, thioglycolate broth, Sabouraud dextrose
      agar, and Ogawa media were used for bacterial, fungal, and mycobacterial
      cultures. MAIN OUTCOME MEASURES: Minimum inhibitory concentrations (MICs) of
      ofloxacin (OFX), levofloxacin (LEV), gatifloxacin (GAT), moxifloxacin (MOX),
      gemifloxacin (GEM), and other commonly used antibiotics were determined using an
      E test. RESULTS: From 105 patients, 73 (85%) coagulase-negative staphylococci
      (CNS), 2 (2.3%) Staphylococcus aureus, 1 (1.2%) Streptococcus pneumoniae, and 5
      (4.8%) gram-negative bacilli were isolated. No fungi or mycobacteria were
      isolated. The MIC that would inhibit the growth of 90% of the tested bacterial
      isolates (MIC(90)) of OFX, LEV, GAT, MOX, and GEM for methicillin-susceptible CNS
      (n = 46) were 0.5 microg/ml, 0.19 microg/ml, 0.094 microg/ml, 0.047 microg/ml,
      and 0.023 microg/ml, respectively. The MIC(90) values for methicillin-resistant
      CNS (n = 27) were 32 microg/ml, 4 microg/ml, 1 microg/ml, 0.5 microg/ml, and 0.25
      microg/ml, respectively (P<0.001). CONCLUSIONS: The most effective against
      conjunctival bacteria isolated from refractive surgery patients were GEM, MOX,
      and GAT; however, resistance to earlier-generation fluoroquinolones (OFX and LEV)
      is increasing among methicillin-resistant CNS. It may be a therapeutic option to
      use newer fluoroquinolones in patients undergoing refractive eye surgery to
      reduce such infections as methicillin-resistant CNS. FINANCIAL DISCLOSURE(S): The
      author(s) have no proprietary or commercial interest in any materials discussed
      in this article.

PMID- 19395039
TI  - American Joint Committee on Cancer classification predicts outcome of patients
      with lacrimal gland adenoid cystic carcinoma.
AB  - PURPOSE: To investigate whether American Joint Committee on Cancer (AJCC)
      classification at initial diagnosis of lacrimal gland adenoid cystic carcinoma
      predicts outcome of treatment on local recurrence. DESIGN: Retrospective chart
      review. PARTICIPANTS: Consecutive patients with adenoid cystic carcinoma of the
      lacrimal gland treated at 8 institutions between January 1986 and December 2007.
      METHODS: Clinical records, including pathology reports and imaging studies, were
      reviewed. MAIN OUTCOME MEASURES: AJCC classification, histologic subtype, local
      recurrence rate, and survival. RESULTS: AJCC classification at initial diagnosis
      was assessable for 53 patients and was as follows: T1N0M0, 7 patients; T2N0M0, 8
      patients; T3aN0M0, 14 patients; T3aNxM0, 1 patient; T3aN0M1, 1 patient; T3bN0M0,
      13 patients; T3bN0M1, 1 patient; T4aN0M0, 2 patients; T4bN0M0, 4 patients;
      T4bN0M1, 1 patient; and T4bNXM0, 1 patient. Thirty-eight (72%) of the 53 patients
      had >T3 tumors at presentation. Of the 38 patients with >T3 tumors, 20 were
      treated with orbital exenteration and postoperative adjuvant radiotherapy (RT), 6
      were treated with orbital exenteration without RT, and 12 were treated with globe
      preserving surgery (10 with RT and 2 without RT). Of the 15 patients with <T3
      tumors, 6 were treated with globe-preserving surgery and RT, 2 were treated with
      globe-preserving surgery without RT, 6 were treated with orbital exenteration
      with bone removal and RT, and 1 was treated with orbital exenteration with bone
      removal without RT. Only 1 patient with a <T3 tumor, had local recurrence. Among
      patients with >T3 tumors, the risk of local recurrence (in the orbit or skull
      base) was higher in patients treated with conservative surgery as opposed to
      orbital exenteration and RT. Only 4 (20%) of the 20 patients treated with orbital
      exenteration and RT had local recurrence, compared with 3 (50%) of the 6 patients
      treated with orbital exenteration without RT and 8 (67%) of the 12 patients
      treated with globe-preserving surgery. Overall, 17 (45%) of the 38 patients with
      >T3 tumors and only 1 (7%) of the 15 patients with <T3 tumors died of disease
      during the study period. CONCLUSIONS: In patients with lacrimal gland adenoid
      cystic carcinoma, AJCC >T3 disease at initial diagnosis correlates with worse
      outcomes than does AJCC <T3 disease. FINANCIAL DISCLOSURE(S): The author(s) have
      no proprietary or commercial interest in any materials discussed in this article.

PMID- 19395040
TI  - Metabolic risk factors in a cohort of young adults and their association with a
      body-mass index between 22 and 25 kg/m2.
AB  - BACKGROUND AND OBJECTIVES: Although health risks associated to excessive body fat
      increase with small increases in body weight, measurement of body fat is usually
      grouped in very few categories. The aim of our study was to assess whether the
      risk for a combined end-point including the incidence of either hypertension
      and/or type 2 diabetes mellitus and/or the metabolic syndrome was elevated even
      within the "normal" limits of body-mass index (BMI). MATERIAL AND METHODS: We
      followed up 10,639 initially healthy university graduates participating in the
      SUN dynamic cohort for a variable period ranging 2 to 6 years. Baseline BMI and
      physical activity were the major exposures. The combined end-point was defined by
      the incidence of either hypertension and/or type 2 diabetes and/or the metabolic
      syndrome during the follow-up period. We fitted non-conditional logistic
      regression models and nonparametric regression models (restricted cubic splines).
      RESULTS: We observed 768 incident cases of the combined outcome (incidence of
      16/1000 person-years) and found a monotonic linear association between BMI and
      the combined end-point. The multivariate-adjusted odds ratios for the combined
      end-point were 1.4 (95% CI: 1.1-1.7) for BMI 22-24.9 kg/m2, 2.7 (2.1-3.5) for 25
      29.9 kg/m2 and 4.0 (2.8-5.6) for 30 kg/m2. We observed a threshold effect in the
      association between physical activity and the combined end-point multivariate
      adjusted odds ratio=0.8 (0.7-0.9) for >15 METs-h/week. CONCLUSIONS: Our findings
      suggest that the incidence of metabolic risk factors (hypertension, diabetes
      mellitus and/or metabolic syndrome) is already increased at a BMI of 22 kg/m2 in
      young adults. These results deserve consideration for judging whether the cut-off
      point for "normal" weight should be lowered.

PMID- 19395041
TI  - Zinc complexes of the antibacterial drug oxolinic acid: structure and DNA-binding
      properties.
AB  - The neutral mononuclear zinc complexes with the quinolone antibacterial drug
      oxolinic acid in the absence or presence of a nitrogen donor heterocyclic ligand
      2,2'-bipyridine or 1,10-phenanthroline have been synthesized and characterized.
      The experimental data suggest that oxolinic acid is on deprotonated mode acting
      as a bidentate ligand coordinated to the metal ion through the ketone and one
      carboxylato oxygen atoms. The crystal structures of (chloro)(oxolinato)(2,2'
      bipyridine)zinc(II), 2, and bis(oxolinato)(1,10-phenanthroline)zinc(II), 3, have
      been determined with X-ray crystallography. The biological activity of the
      complexes has been evaluated by examining their ability to bind to calf-thymus
      DNA (CT DNA) with UV and fluorescence spectroscopies. UV studies of the
      interaction of the complexes with DNA have shown that they can bind to CT DNA and
      the DNA-binding constants have been calculated. Competitive studies with ethidium
      bromide (EB) have shown that complex 3 exhibits the ability to displace the DNA
      bound EB indicating that it binds to DNA in strong competition with EB.

PMID- 19395042
TI  - [Calcification in metastatic cervical adenopathies from squamous cell carcinoma].
AB  - We report a case of hypopharyngeal squamous cell carcinoma with multiple
      calcified metastatic cervical adenopathies, and we review the relevant
      literature. The finding of calcified metastatic adenopathies from squamous cell
      carcinoma in the head and neck is very uncommon; only three cases have been
      reported to date.

PMID- 19395044
TI  - [Solution to case 4. Reactivation of tuberculosis in an oleothorax.].

PMID- 19395045
TI  - Meat juice: An alternative matrix for assessing animal health by measuring acute
      phase proteins. Correlations of pig-MAP and haptoglobin concentrations in pig
      meat juice and plasma.
AB  - Quantification of acute phase proteins (APPs) in blood can be used for monitoring
      animal health and welfare on farms, and could be also of interest for the
      detection of diseased animals during the meat inspection process. However serum
      or plasma is not always available for end-point analysis at slaughter. Meat juice
      might provide an adequate, alternative matrix that can be easily obtained for
      post-mortem analysis at abattoirs. The concentrations of pig Major Acute phase
      Protein (pig-MAP) and haptoglobin, two of the main APPs in pigs, were determined
      in approximately 300 paired samples of plasma and meat juice from the diaphragm
      (pars costalis), obtained after freezing and thawing the muscle. APPs
      concentrations in meat juice were closely correlated to those in plasma (r=0.695
      for haptoglobin, r=0.858 for pig-MAP, p<0.001). These results open new
      possibilities for the assessment of animal health in pig production, with
      implications for food safety and meat quality.

PMID- 19395046
TI  - A psychological autopsy study of pathological gamblers who died by suicide.
AB  - BACKGROUND: Pathological gambling is associated with suicidal ideation and
      attempt. There is no known report on pathological gambling preceding suicide. By
      examining a series of 17 suicide cases with evidence of pathological gambling
      prior to death, we sought to generate hypotheses for further study of this under
      researched but rapidly-increasing worldwide public health problem. METHOD:
      Psychological autopsy interviews using a semi-structured format were conducted
      with proxy respondents for suicide and control subjects aged 15-59 years in Hong
      Kong SAR, China. RESULTS: Of the 150 suicides and 150 controls examined, 17
      suicides (11.3%) and one control case (0.6%) met criteria for the diagnosis of
      pathological gambling at the time of death or interview. All 17 suicide cases
      with pathological gambling had unmanageable debt at the time of death. Fourteen
      cases (82.4%) had other associated psychiatric disorders, most often major
      depressive disorders (n=10, 58.9%) and substance-use disorders (n=3, 17.6%). None
      had ever received psychiatric treatment. LIMITATIONS: Descriptive, retrospective
      case series with a small sample size. CONCLUSIONS: Along with unmanageable debt,
      a high proportion of the suicide cases with pathological gambling also
      experienced other psychiatric illnesses, most often depression, at the time of
      death. None sought treatment for their addictive behavior or psychiatric illness
      prior to death. Pathological gambling is a modifiable risk factor for suicide for
      which means to enhance case identification and engagement in treatment are
      urgently needed. Clinicians treating depression should explore the presence of
      pathological gambling behavior or unmanageable debts among their patients.
      Addressing pathological gambling should be one important component of a
      comprehensive suicide prevention strategy especially in countries where gambling
      activities are legalized and expanding.

PMID- 19395048
TI  - Completed suicide in schizophrenia: evidence from a case-control study.
AB  - Suicide is the single major cause of death among patients with schizophrenia.
      Despite great efforts in the prevention of such deaths, suicide rates have
      remained alarming, pointing to the need for a better understanding of the
      phenomenon. The present sample comprised 20 male patients with schizophrenia who
      committed suicide and who were investigated retrospectively for a large number of
      characteristics. Controls were 20 living patients with schizophrenia. The results
      suggest that suicide attempts, hopelessness and self-devaluation were the three
      variables most strongly associated with completed suicide. However, a number of
      variables were identified which may constitute risk factors, some of which have
      not been identified in the past: agitation and motor restlessness (OR = 3.66;
      95%CI = 0.95/14.02), self-devaluation (OR = 28.49; 95%CI = 3.15/257.40),
      hopelessness (OR = 51.00; 95%CI = 7.56-343.72), insomnia (OR = 12.66; 95%CI =
      0.95/14.02), mental disintegration (OR = 3.66; 95%CI = 0.95/14.02), and suicide
      attempt (OR = 3.66; 95%CI = 1.40/114.41). Poor adherence to medications was also
      predictive of completed suicide in our sample of schizophrenia patients,
      primarily because the suicide victims showed very low adherence.

PMID- 19395047
TI  - Electrophysiological manifestations of stimulus evaluation, response inhibition
      and motor processing in Tourette syndrome patients.
AB  - Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder with
      childhood onset presenting with multiple fluctuating motor tics and one or more
      phonic tics. A significant proportion of people suffering from GTS are still
      symptomatic in adulthood and present other emotional and cognitive difficulties,
      along with motor problems that often accompany these comorbid conditions. The
      nature of these difficulties is still poorly understood and multiple
      comorbidities are often inadequately controlled. The current study investigates
      both stimulus evaluation and motor processing in GTS while controlling for
      comorbidity. Fifteen adults with GTS and 20 control participants were matched on
      gender, laterality and intelligence. The P300 component, the no-go
      anteriorization (NGA) as well as the stimulus and response-locked lateralized
      readiness potentials (S-LRP, R-LRP) were elicited during a stimulus-response
      compatibility (SRC) paradigm. The standard version of the Stroop Color-Word Test
      (SCWT) was also administered. Reaction times showed that participants with GTS
      processed both the SRC and the SCWT more rapidly than the control group, while
      producing a delayed P300 peak latency. The GTS group also showed faster S-LRP
      onset in response to the incompatible and faster processing of interference in
      the SCWT. There was also a tendency toward a greater frontal shift of the NGA in
      the GTS group. The P300 latency showed that with GTS patients, stimulus
      evaluation occurs later whereas the overlapping pre-motor response selection
      processes occur faster. Our findings are congruent with a probable cortical motor
      over-activation hypothesis of GTS involving faster motor program selection in
      processing conflicting SR configuration.

PMID- 19395049
TI  - Insight and executive functioning in schizophrenia: a multidimensional approach.
AB  - Past research suggests that unawareness of illness in schizophrenia is associated
      with deficits in executive functions; however, the relationships between
      executive processes and the various dimensions of insight are still unclear.
      Recent models of executive functioning have proposed that four executive
      processes - inhibition, updating, shifting and dual task coordination - are
      moderately related yet separable. In this study, we proposed to investigate and
      clarify the relationships between insight dimensions and the aforementioned four
      executive components. A total of 60 patients were administered the Test for
      Attentional Performance and the Scale to Assess Unawareness of Mental Disorder.
      The effect of potential confounding variables such as medication, symptomatology,
      demography, psycho-affective state, and general processing speed were also
      examined in a preliminary statistical analysis. We found that both awareness of
      disorder and awareness of response to medication were significantly related to
      Updating. Awareness of the social consequences of the disease was significantly
      related to Updating, Divided Attention and Inhibition Processes. The analysis
      indicates that poor insight in schizophrenia may be partially related to
      executive dysfunction. Finally, our study emphasizes the possible role of
      neuropsychological intervention in improving patients' insight into illness.

PMID- 19395050
TI  - Differential association of socioeconomic status in ethnic and age-defined
      suicides.
AB  - Suicide rates vary among racel- and age-defined groups, yet little is known about
      how suicide risk factors differentially impact individual groups. This study
      assessed differential associations of socioeconomic status among age- and race
      defined groups of suicide victims. A database containing demographic information
      on declared suicides in Fulton County, GA, from 1 January 1988 through 31
      December 2003 was combined with annual per capita income by zip code in Atlanta,
      GA. Analyses were performed to evaluate differential associations of
      socioeconomic status among age- and race-defined groups of suicide victims.
      Compared with the respective ethnic populations of Fulton County, white suicide
      victims lived in areas with lower per capita income ($51,232 vs. $35,893);
      African American suicide victims did not ($17,384 vs. $18,179). Elderly suicide
      victims (>or= 65 years) were more likely to live in the lowest per capita income
      areas compared with other age groups (OR 1.80, 95% C.I. 1.14, 2.84). Cox
      proportional hazards models showed increasing income increased the instantaneous
      risk of suicide among adolescents (HR 2.76; 95% C.I. 2.15, 3.53), particularly
      African American adolescents (HR 4.22; 95% C.I. 2.19, 8.11), and decreased risk
      among the elderly (HR 0.58; 95% C.I. 0.50, 0.68). Socioeconomic status had
      differential associations among age- and race-defined groups of suicide victims.

PMID- 19395051
TI  - Diminished P50, N100 and P200 auditory sensory gating in bipolar I disorder.
AB  - Bipolar I disorder is associated with diminished gating of the auditory evoked
      P50 component. P50 gating may relate to early filtering of sensory information,
      protecting higher-order cognitive functions. Gating of the auditory evoked N100
      and P200 components has not been investigated in bipolar I disorder, although
      N100 and P200 gating could reflect different mechanisms and functions in the
      process of filtering sensory information in addition to those reflected by P50
      gating. We investigated P50, N100, and P200 gating assessed with the paired-click
      paradigm in 22 subjects with bipolar I disorder and 54 healthy controls. Peak
      amplitudes and latencies were assessed at Cz for the P50, N100, and P200
      components. Gating was defined as the reduction in peak amplitude from the first
      (S1) to the second stimulus (S2) of a stimulus pair, and expressed as gating
      ratio ([S2(amplitude)/S1(amplitude)]()100) and difference score (S1(amplitude)
      S2(amplitude)). Group differences were detected with multivariate analyses and
      controlled for differences in age and ethnicity. Subjects with bipolar I disorder
      had higher P50, N100 and P200 ratios and lower difference scores compared with
      findings for controls. These findings extend the existing evidence on impaired
      sensory gating in bipolar I disorder beyond the P50, suggesting impaired
      filtering at both pre-attentive and early attentive levels in bipolar I disorder.

PMID- 19395052
TI  - The risk factors of Internet addiction--a survey of university freshmen.
AB  - This study was designed to explore the risk factors of Internet addiction in 1360
      freshmen of the National Cheng Kung University in Taiwan in 2003. The test
      battery included a self-administrated structured questionnaire, the Chinese
      Internet Addiction Scale-Revision (CIAS-R), the 12-item Chinese Health
      Questionnaire (CHQ-12), the Measurement of Support Functions (MSF), and the
      neuroticism subscale of the Maudsley Personality Inventory (MPI). Of the total
      study population, there were 680 college freshmen (17.9%) in the Internet
      addiction group, as defined by high CIAS-R scores. Using logistic regression
      analyses, we found positive relationships between Internet addiction and male
      gender, neuroticism scores and the CHQ score. In addition, the freshmen who
      skipped breakfast and those who had poorer social support also had a higher
      probability of Internet addiction. Internet addiction is prevalent among
      university freshmen in Taiwan. Risk factors included male gender, habit of
      skipping breakfast, mental health morbidity, deficient social support; and
      neurotic personality characteristics.

PMID- 19395053
TI  - Dynamic properties of an omni-directional piezoelectric motor for precision
      position control.
AB  - A piezoelectric motor capable of omni-directional movements has been developed to
      apply for robot joints, eyes, and precision positioning stage. The piezoelectric
      actuator has a simple structure of a cone type consisting of two piezoelectric
      ring-typed ceramics with electrodes divided into four segments and stainless
      steel elastic bodies. Before manufacturing the piezoelectric motor, the
      admittance characteristics and displacements of the actuator as a function of
      frequency were simulated. Elliptical motions of the actuator were created at
      several frequencies between the longitudinal and transverse resonance
      frequencies. The actual motor with alumina ball exhibited nice performance using
      a driving circuit with two rotary encoders and a PID controller. The moving
      element was omni-directionally operated at a driving frequency of 53.8 kHz and an
      output voltage of 280 V(p-p). The developed motor enables the moving element to
      move to a desired position with a resolution of 1.2 degrees/pulse, an angular
      velocity of 4 rad/s, and a thrust force of 200 g.

PMID- 19395054
TI  - The nsP3 macro domain is important for Sindbis virus replication in neurons and
      neurovirulence in mice.
AB  - Sindbis virus (SINV), the prototype alphavirus, contains a macro domain in the
      highly conserved N-terminal region of nonstructural protein 3 (nsP3). However,
      the biological role of the macro domain is unclear. Mutations of amino acids 10
      and 24 from asparagine to alanine in the ADP-ribose binding region of the macro
      domain impaired SINV replication and viral RNA synthesis particularly in neurons,
      but did not alter binding of poly(ADP-ribose). Mutation at position 10 had the
      greatest effect and caused nsP3 instability in neurons, decreased SINV-induced
      death of mature, but not immature neurons, and attenuated virulence in 2 week
      old, but not 5 day-old mice. A compensatory mutation at amino acid 31 in the
      macro domain of nsP3, as well as reversion of mutated amino acid 10, occurred
      during replication of double mutant SINV in vitro and in vivo. The nsP3 macro
      domain is important for SINV replication and age-dependent susceptibility to
      encephalomyelitis.

PMID- 19395055
TI  - A temperature sensitive VSV identifies L protein residues that affect
      transcription but not replication.
AB  - To investigate the polymerase components selectively involved in transcription
      versus replication of vesicular stomatitis virus (VSV), we sequenced the
      polymerase gene of a conditionally RNA defective, temperature sensitive VSV:
      ts(G)114, which has a phenotype upon shift from permissive to non-permissive
      temperature of shut-down of mRNA transcription and unaffected genome replication.
      Sequence analysis of the ts(G)114 L gene identified three altered amino acid
      residues in the L protein. These three changes were specifically engineered
      individually and in combinations into a functional cDNA clone encoding the VSV
      genome and tested for association with the temperature sensitive and RNA
      defective phenotypes in the background of recovered engineered viruses. The data
      presented in this study show a specific amino acid substitution in domain II of
      the VSV L protein that significantly affects total RNA synthesis, but when in
      combination with two additional amino acid substitutions identified in the
      ts(G)114 L protein, leads to a specific reduction in mRNA transcription, but not
      replication.

PMID- 19395057
TI  - Pediatric tracheotomies: a 37-year experience in 282 children.
AB  - OBJECTIVE: To study the outcomes, complications, and indications for pediatric
      tracheotomies performed at a tertiary referral center. METHODS: A retrospective
      review of hospital records from 1968 to 2005 was conducted to assess all
      pediatric patients who had undergone tracheotomies. RESULTS: A total of 282
      tracheotomies were performed on patients under 16 years of age. The median age at
      tracheotomy was 27 months. Upper airway obstruction (infectious diseases, n=101;
      laryngeal anomalies, n=33; trauma, n=36; tumor, n=33) was the most common
      indication for tracheotomy (n=203; 72%). Lesser number of patients (n=79; 28%)
      required tracheotomy for prolonged ventilation. Decannulation was carried out
      successfully in 71 patients (35%). Total complication rate was 18%; only three
      patients (1%) died from tracheotomy-related complications, with an overall
      mortality rate of 19%. CONCLUSIONS: Pediatric tracheotomies were associated with
      a low incidence of procedure-related mortality and morbidity and successful
      decannulation in 35% of cases. The majority of procedures were performed due to
      upper airway obstruction which were most commonly caused by infectious diseases.

PMID- 19395056
TI  - Inhibition of Vaccinia virus entry by a broad spectrum antiviral peptide.
AB  - Concerns about the possible use of Variola virus, the causative agent of
      smallpox, as a weapon for bioterrorism have led to renewed efforts to identify
      new antivirals against orthopoxviruses. We identified a peptide, EB, which
      inhibited infection by Vaccinia virus with an EC(50) of 15 microM. A control
      peptide, EBX, identical in composition to EB but differing in sequence, was
      inactive (EC50>200 microM), indicating sequence specificity. The inhibition was
      reversed upon removal of the peptide, and EB treatment had no effect on the
      physical integrity of virus particles as determined by electron microscopy. Viral
      adsorption was unaffected by the presence of EB, and the addition of EB post
      entry had no effect on viral titers or on early gene expression. The addition of
      EB post-adsorption resulted in the inhibition of beta-galactosidase expression
      from an early viral promoter with an EC(50) of 45 microM. A significant reduction
      in virus entry was detected in the presence of the peptide when the number of
      viral cores released into the cytoplasm was quantified. Electron microscopy
      indicated that 88% of the virions remained on the surface of cells in the
      presence of EB, compared to 37% in the control (p<0.001). EB also blocked fusion
      from-within, suggesting that virus infection is inhibited at the fusion step.
      Analysis of EB derivatives suggested that peptide length may be important for the
      activity of EB. The EB peptide is, to our knowledge, the first known small
      molecule inhibitor of Vaccinia virus entry.

PMID- 19395058
TI  - Effect of cryopreservation on proliferative features of neural progenitor cells
      derived from olfactory bulb of embryonic rat.
AB  - OBJECTIVE: Stem cell research offers unique opportunities for developing new
      medical therapies for devastating diseases and a new way to explore fundamental
      questions of biology. The use of olfactory bulb neural progenitor cells for
      transplantation requires efficient recovery methods and cryopreservation
      procedures. The purpose of this study was to determine cryopreservation
      techniques for neural progenitor cells derived from olfactory bulb (OB NPCs) of
      embryonic rat. METHODS: Initially, we compared the survival rates of
      cryopreserved OB NPCs using three cryoprotectants: dimethyl sulfoxide (DMSO),
      ethylene glycol (EG) and glycerol with or without 10% FBS. Cells were held at
      liquid nitrogen (-186 degrees C) for 7 days ("short-term storage") or 6 months
      ("long-term storage"). We assessed OB NPCs recovery efficiency after freezing and
      thawing by viability testing, colony-forming ability and immunocytochemistry
      under different conditions. RESULTS: The survival rate of cryopreserved-thawed OB
      NPCs was estimated by counting colony numbers under a stereomicroscope. No
      significant difference in survival rate was observed between cryoprotectants.
      CONCLUSIONS: These observations indicate that cryopreservation of OB NPCs is
      possible for up to 6 months in optimal conditions without losing proliferation
      activity.

PMID- 19395059
TI  - Nasal leech infestation in children: comparison of two different innovative
      techniques.
AB  - OBJECTIVE: The objective of this study is to compare the results of two different
      techniques in removing nasal leech infestation. MATERIAL AND METHODS: This
      prospective study was carried out in 40 patients attending Department of ENT and
      Head and Neck Surgery, TU Teaching Hospital, Kathmandu, with the history
      suggestive of nasal leech infestation. Patients enrolled between April 2004 and
      December 2008 were studied. Patients were arranged randomly into two groups. In
      the first group of patients, anterior rhinoscopy was done and suction was used to
      remove the leech from nasal cavity. While in second group, water was poured into
      the kidney tray and adjusted 1cm below the nasal vestibule. As soon as the leech
      was seen in the nasal vestibule coming towards the water, they were catched with
      artery forceps. Both groups were compared in the following items: time taken to
      remove the leech, bleeding status, pain assessment and patient's/caretaker's
      satisfaction. Unpaired t test was applied to compare the time taken in removing
      leeches in both groups. RESULTS: In the first group of patients using suction,
      the mean duration of removal of leech was 18.25 min while in second group of
      patients, it was 30.25 min. Bleeding and pain was present in the first group of
      patients. All children were not satisfied with this technique in first group of
      patients. Around 70% of the patients wanted an easier option to remove the leech
      from nasal cavity. CONCLUSION: Wait and watch policy (keeping the water in kidney
      tray just below the nasal vestibule) is a better technique because of less pain
      and less blood loss with full satisfaction to the patients and caretakers, though
      it is more time consuming.

PMID- 19395060
TI  - Calibrating and validating bacterial water quality models: a Bayesian approach.
AB  - Water resource management decisions often depend on mechanistic or empirical
      models to predict water quality conditions under future pollutant loading
      scenarios. These decisions, such as whether or not to restrict public access to a
      water resource area, may therefore vary depending on how models reflect process,
      observation, and analytical uncertainty and variability. Nonetheless, few
      probabilistic modeling tools have been developed which explicitly propagate fecal
      indicator bacteria (FIB) analysis uncertainty into predictive bacterial water
      quality model parameters and response variables. Here, we compare three
      approaches to modeling variability in two different FIB water quality models. We
      first calibrate a well-known first-order bacterial decay model using approaches
      ranging from ordinary least squares (OLS) linear regression to Bayesian Markov
      chain Monte Carlo (MCMC) procedures. We then calibrate a less frequently used
      empirical bacterial die-off model using the same range of procedures (and the
      same data). Finally, we propose an innovative approach to evaluating the
      predictive performance of each calibrated model using a leave-one-out cross
      validation procedure and assessing the probability distributions of the resulting
      Bayesian posterior predictive p-values. Our results suggest that different
      approaches to acknowledging uncertainty can lead to discrepancies between
      parameter mean and variance estimates and predictive performance for the same FIB
      water quality model. Our results also suggest that models without a bacterial
      kinetics parameter related to the rate of decay may more appropriately reflect
      FIB fate and transport processes, regardless of how variability and uncertainty
      are acknowledged.

PMID- 19395061
TI  - Quantification of Giardia transcripts during in vitro excystation: interest for
      the estimation of cyst viability.
AB  - The aim of the present study was to evaluate the potential of transcript
      quantification as an indicator of Giardia cyst viability. The variations of beta
      giardin, EF1A and ADHE mRNAs were quantified during excystation by real-time RT
      PCR assays and compared with the percentages of viability estimated using
      propidium iodide staining and in vitro excystation. The first experiments were
      performed with purified G. duodenalis assemblage B cysts. When 55% of excysting
      protozoa were observed, the increase of the selected transcripts ranged from
      0.40+/-0.13 to 0.97+/-0.11 log10 after 1h of incubation in excystation medium.
      Purified cysts were also stored at 4 degrees C for up to 56 days and analysed at
      several sampling times. Significant correlations were observed between the
      variations of the selected mRNAs and the percentages of viability estimated with
      staining and excystation methods. Among the three transcripts, beta-giardin
      appeared to be the most appropriate to study the viability of Giardia cysts
      concentrated from wastewater samples.

PMID- 19395062
TI  - Occurrence of pharmaceuticals and personal care products along the West Prong
      Little Pigeon River in east Tennessee, USA.
AB  - Presence of pharmaceuticals and personal care products (PPCPs) in the environment
      has received a great attention due to their potential impacts on public health.
      This study examined the occurrence of PPCPs in West Prong Little Pigeon River in
      east Tennessee. As wastewater is a major source for environmental occurrence of
      PPCPs, both wastewater and river water samples were analyzed for nine target
      PPCPs and their estrogenicity. No estrogens were detected in influent, secondary
      effluent, and river samples. However, ibuprofen, caffeine, triclosan, bisphenol
      A, and bis(2-ethylhexyl)phthalate (DEHP) were detected in the influent.
      Ibuprofen, triclosan, and DEHP were detected in the secondary effluent samples.
      Only ibuprofen and triclosan were detected in river water collected near a
      wastewater outfall. Based on yeast estrogenic screening (YES) assays, estrogenic
      activities were observed in all influent, secondary effluent, and river water
      samples. Increased estrogenic activities were observed in river right after
      receiving effluent discharge, and the activities decreased as river water flowing
      away from the outfall. The estrogenicities of water samples measured from YES
      assays were much higher than those estimated from PPCP concentrations and their
      known estrogenicities, suggesting the presence of other unknown estrogenic
      compounds and/or additive effects of mixtures of estrogenic compounds at low
      concentrations. Results of this study demonstrated that wastewater contributed to
      environmental occurrence of PPCPs in the receiving water. As there is a myriad of
      known and unknown PPCPs in wastewater, in additional to chemical analysis,
      estrogenic bioassays are needed for assessing estrogenicity of environmental
      samples.

PMID- 19395063
TI  - Temperature-dependence of soil/air partition coefficients for selected polycyclic
      aromatic hydrocarbons and organochlorine pesticides over a temperature range of 
      30 to +30 degrees C.
AB  - The soil/air partition coefficients (K(SA)) for two polycyclic aromatic carbons
      (PAHs) and six organochlorine pesticides (OCs) were determined by a solid-phase
      fugacity meter over a wide temperature range of -30 to +30 degrees C in a paddy
      field soil. Literature values for PAHs and OCs obtained by the same method were
      1.9-5.1 times of present values at +20 degrees C. Experimentally determined K(SA)
      ranged over six orders of magnitude, with log K(SA) from 4.5 for alpha
      hexachlorocyclohexane at +30 degrees C to 10.4 for trans-nonachlor at -20 degrees
      C. Separate linear regressions of log K(SA) and reciprocal absolute temperature
      were employed at temperatures above 0 degrees C and below 0 degrees C. The
      calculated enthalpies associated with the phase transfer from the soil to the air
      (DeltaH(SA)) over 0 to +30 degrees C range from 78 to 108 kJmol(-1), which are in
      a good agreement with the literature values.

PMID- 19395064
TI  - PBDEs in sediments of the Beijiang River, China: levels, distribution, and
      influence of total organic carbon.
AB  - Forty surface and twenty-two deeper sediment samples were collected from the
      Beijiang River and analyzed to acquire information about the levels,
      distribution, possible sources and influencing factors of polybrominated diphenyl
      ethers (PBDEs) in the Beijiang River. Our results showed that the most abundant
      BDE congeners in surface sediments were BDE47, 99 and 209, with a median value of
      0.044, 0.03, and 5.22 ng g(-1), respectively. The levels of BDE209 in our samples
      were much higher relative to those of the other BDE congeners and made up more
      than 90% of the PBDEs levels in almost all samples. Disregarding BDE209, of the
      remaining 9 BDE congeners the most abundant ones were BDE47 and 99, which
      contributed 35.7% and 24.6%, respectively, to the median of the 9 congeners. The
      contribution of the Beijiang River to the PBDE pollution burden of the Pearl
      River Delta (PRD) was small in comparison to that of the Dongjiang River and the
      Guangzhou section of the Zhujiang River. PBDEs in the Beijiang River mainly came
      from use of deca-BDE and penta-BDE with a minor contribution of octa-BDE. The
      poor correlation between PBDE and TOC may indicate that PBDEs concentrations in
      the sediments of the Beijiang River were controlled not only by TOC contents, but
      also by a combined effect of transport, mixing, depositional mechanisms
      associated with PBDEs, uncontaminated sediments, or fresh input of PBDEs.

PMID- 19395065
TI  - Fate of nonylphenol polyethoxylates and their metabolites in four Beijing
      wastewater treatment plants.
AB  - Four Beijing wastewater treatment plants (WWTPs) were selected to investigate
      behaviours of nonylphenol polyethoxylates and their metabolites in different
      wastewater treatment processes. The results showed that the total concentrations
      of nonylphenolic compounds in the influents of the four WWTPs ranged from 0.115
      to 0.347 mumol/L, as well as their removal efficiencies ranging from 75.7% to
      90.8%. Both influent concentrations and removal efficiencies of nonylphenol
      polyethoxylates were correlated to seasons as follows: higher in the summer than
      in the winter, and influent concentrations were lower during the rain weather.
      The analysis revealed that 21.8-47.6% of nonylphenol polyethoxylates and their
      metabolites entering WWTPs were released via effluents and excess sludge, leaving
      a great part of them for biodegradation. Nonylphenol and short-chain nonylphenol
      polyethoxylates were disposed to the environment mainly via sewage sludge, while
      carboxylated nonylphenol polyethoxylates were the most abundant group of
      nonylphenol polyethoxylates in effluents.

PMID- 19395066
TI  - Analysis of dissolved microcystins in surface water samples from Kovada Lake,
      Turkey.
AB  - Dissolved (extracellular) microcystin (MC) concentrations were determined at 3
      sampling stations on Lake Kovada, Turkey. The dominant species of cyanobacteria
      found in August and September of 2006 were Microcystis aeruginosa, Synechococcus
      sp., Phormidium limosum, Phormidium formosa and Planktothrix limnetica. MC
      concentrations in water were measured by ELISA and MC variants were examined by
      HPLC-PDA. Quantitative analysis by HPLC indicated that five MC variants (MC-LR, 
      RR, -LA, -LW, -LF) were identified in water samples from Kovada Lake. The maximum
      concentration of dissolved MC-LW was 98.9 microg l(-1) in October. MC-LR was only
      detected in May at a concentration of 0.5 microg l(-1). The cross reactivity of
      the antibody (MC10E7) to variants such as MC-LA MC-LW & MC-LF was low. Hence the
      results determined by ELISA were lower than those determined by HPLC in September
      and October samples due to differences in the specificity of the antibody to MC
      variants. Total extracellular MCs was quantified by ELISA and ranged from 0.73 to
      48.5 microg MC-LR equivalents l(-1), which in some cases exceeded the WHO
      provisional Guideline Value for MC-LR in drinking water. This study confirms that
      the lakes of Turkey should be monitored for toxic cyanobacteria and for MCs to
      avoid or reduce the potential exposure of people to these health hazards.

PMID- 19395067
TI  - Assessment of emerging and traditional halogenated contaminants in Guillemot
      (Uria aalge) egg from North-Western Europe and the Baltic Sea.
AB  - Persistent organic pollutants (POPs) are readily detected in biological samples
      at remote sites in the Arctic and sub-Arctic due to long-range transport from
      source areas. The aim of this study was to investigate the presence of POPs,
      polybrominated contaminants and their metabolites in guillemot (Uria aalge) eggs
      from Iceland, the Faroe Islands, Norway and Sweden to assess spatial trends of
      these compounds in the Arctic and sub-Arctic areas of Europe. Egg samples were
      extracted, and cleaned for chemical analysis. Concentrations of PCBs, 4,4'-DDE
      and beta-HCH were an order of magnitude higher in eggs from the Baltic Proper
      compared to eggs from the North Atlantic. Concentrations of HCB were of the same
      magnitude at all sites, ranging from 160 to 520 ng/g fat. Concentration of BCPS
      was 100 times higher in eggs from the Baltic compared to eggs from the North
      Atlantic and seems therefore to be special regional problem. Concentrations of
      PBDEs were lower in eggs from the North Atlantic compared to eggs from the Baltic
      Proper but the difference was not as large as for PCBs and 4,4'-DDE. HBCDD showed
      the same spatial trend as PCBs, where the concentrations in eggs from the Baltic
      Proper were an order of magnitude higher than in eggs from the North Atlantic. OH
      PCB and MeSO(2)-PCB metabolites of PCBs, showed the same trend as the parent
      compounds while spatial trends of MeSO(2)-DDE and OH-PBDEs, metabolites of 4,4'
      DDE and PBDEs, respectively, differed from the trend of the parent compounds.
      This may be due to two factors; firstly, the limited ability of birds to
      metabolise DDT, and secondly, to natural production of OH-PBDE, respectively.
      Guillemot is suggested as a monitoring species for circumpolar monitoring.

PMID- 19395068
TI  - Blood lead levels of children and its trend in China.
AB  - To evaluate Chinese children's blood lead levels (BLLs) and identify its
      distribution features, we collected articles on children's BLLs published from
      Jan, 2004 to Aug, 2007 with sampling time since 2001, by searching Chinese
      Biomedical Disk (CBMDisk), Chinese Journal Full-test Database (CJFD) and other
      ways. After a rigorous investigation, 35 articles eligible for inclusion criteria
      were reviewed. Meanwhile, to reveal the trend of Chinese children's BLLs, the
      data was compared with the results from our former study carried out in 2004,
      which reviewed the articles published since 1995 to 2003. The results showed that
      the mean BLLs of Chinese children from 2001 to 2007 was 80.7 microg/L (45.5-165.3
      microg/L), and 23.9% (3.2%-80.7%) of children's BLLs was higher than 100
      microg/L. Both BLLs and prevalence of BLLs higher than 100 microg/L were lower
      than that of 1995 to 2003. Of 24 provinces or cities, only 4 showed higher BLLs
      and higher prevalence rates of lead poisoning (BLLs > or =100 microg/L) than that
      of 1995 to 2003. The mean BLLs of children living in industrial areas were higher
      than those in urban and suburban areas, and suburban higher than urban areas.
      Boys' BLLs were 79.3 microg/L, significantly higher than girls 76.9 microg/L
      (P<0.001). The results also showed that children's BLLs increased with their
      ages, and the decreased BLLs for all age were observed comparing with the results
      of our former study in 2004. Overall, our study revealed that the BLLs of
      children in China showed a decreasing trend after gasoline with lead was banned
      in China in 1st July 2000. Our study also showed that the BLLs of children in
      China were still higher than that in developed countries, which suggested that
      children's lead poisoning prevention and controlling would be a long-term mission
      in China.

PMID- 19395069
TI  - Chromium(III) induces oxidative stress in goldfish liver and kidney.
AB  - In the environment chromium is found mainly in two valence states-hexavalent
      chromium (Cr6+) and trivalent chromium (Cr3+). The present study evaluates the
      effects of Cr3+ exposure on goldfish by analyzing parameters of oxidative stress
      and antioxidant defense in liver and kidney of fish given 96 h exposures to Cr3+
      concentrations of 1, 2.5, 5 or 10 mg/l in aquarium water. Cr3+ exposure did not
      alter two parameters of oxidative stress-protein carbonyl content and lipid
      peroxide concentrations in either organ. However, Cr3+ exposure did decrease
      total glutathione concentration in liver by 34-69% and in kidney to 36-49% of the
      respective control values. Oxidized GSSG content fell by similar percentages so
      that the ratio [GSSG]/[total glutathione] remained constant at all Cr3+ exposure
      levels except in liver under the highest, 10 mg/l, exposure level. In liver,
      exposure to 1-5 mg/l Cr3+ led to a decrease in the activity of superoxide
      dismutase (SOD) by 29-36%, and at 10 mg/l Cr3+ the reduction was 54%, whereas in
      kidney approximately 30% reductions in SOD activity were seen at concentrations 1
      and 10 mg/l Cr3+. Catalase activity was not significantly affected by 1-5 mg/l
      Cr3+, but was reduced by 57 and 42% in liver and kidney, respectively. Chromium
      exposure also reduced the activity of glutathione-S-transferase in both organs by
      17-50% but did not affect glutathione reductase or glucose-6-phosphate
      dehydrogenase activities. A comparison of Cr3+ effects on goldfish liver and
      kidney metabolism indicates that the trivalent ion induces stronger oxidative
      stress than Cr6+ at the same concentrations.

PMID- 19395070
TI  - Developing a quick and practical screen to improve the identification of poor
      hydration in geriatric and rehabilitative care.
AB  - Dehydration has been associated with increased morbidity and mortality.
      Dehydration risk increases with advancing age, and will progressively become an
      issue as the aging population increases. Worldwide, those aged 60 years and over
      are the fastest growing segment of the population. The study aimed to develop a
      clinically practical means to identify dehydration amongst older people in the
      clinical care setting. Older people aged 60 years or over admitted to the
      Geriatric and Rehabilitation Unit (GARU) of two tertiary teaching hospitals were
      eligible for participation in the study. Ninety potential screening questions and
      38 clinical parameters were initially tested on a single sample (n = 33) with the
      most promising 11 parameters selected to undergo further testing in an
      independent group (n = 86). Of the almost 130 variables explored, tongue dryness
      was most strongly associated with poor hydration status, demonstrating 64%
      sensitivity and 62% specificity within the study participants. The result was not
      confounded by age, gender or body mass index. With minimal training, inter-rater
      repeatability was over 90%. This study identified tongue dryness as a potentially
      practical tool to identify dehydration risk amongst older people in the clinical
      care setting. Further studies to validate the potential screen in larger and
      varied populations of older people are required.

PMID- 19395071
TI  - A prospective randomized trial comparing patient-controlled epidural analgesia to
      patient-controlled intravenous analgesia on postoperative pain control and
      recovery after major open gynecologic cancer surgery.
AB  - OBJECTIVE: To determine the effect of perioperative patient-controlled epidural
      analgesia (PCEA) compared to postoperative intravenous (IV) patient-controlled
      analgesia (PCA) on postoperative recovery parameters after major open gynecologic
      surgery. METHODS: A randomized controlled clinical trial included women
      undergoing laparotomy for a gynecologic disorder. Patients were randomized to
      postoperative IV morphine PCA (control arm) or to postoperative morphine
      bupivacaine PCEA (treatment arm). Postoperative outcomes such as pain, and length
      of hospital stay were compared with an intention-to-treat analysis. The primary
      endpoint was postoperative pain at rest and when coughing--assessed by a 10-point
      visual analog scale (VAS). RESULTS: Between 9/04 and 6/07, 153 patients were
      randomized and 135 were evaluable (PCEA=67; PCA=68). Over 75% of the women in
      this study had gynecologic cancer. Patients in the PCEA arm had significantly
      less postoperative pain at rest on Day 1 and during the first 3 postoperative
      days when coughing compared to the PCA arm (P<0.05). The mean pain score at rest
      on Day 1 was 3.3 for the PCEA group compared to 4.3 for the PCA group (P=0.01).
      Overall, postoperative pain at rest and while coughing in the first 6 days was
      less in women treated with PCEA compared to PCA (P<0.003). CONCLUSIONS: PCEA
      offers superior postoperative pain control after laparotomy for gynecologic
      surgery compared to traditional IV PCA. Women requiring major open surgery for
      gynecologic cancer should be offered PCEA for postoperative pain management if
      there are no contraindications.

PMID- 19395072
TI  - Hyperventilation-induced ST segment elevation mimicking acute myocardial
      infarction in a comatose patient with tracheostomy.
AB  - Controlled hyperventilation leading to respiratory alkalosis may induce coronary
      artery spasm. This manoeuvre is currently used in the diagnosis of Prinzmetal's
      angina. We describe the case of a comatose patient with tracheostomy in whom
      hyperventilation, caused by excessive bronchial secretion resulting in partial
      obstruction of the tracheal cannula, was followed by ST segment elevation
      mimicking acute myocardial infarction.

PMID- 19395073
TI  - Validating a new quality of life questionnaire for atrial fibrillation patients.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia in
      clinical practice, and has major impact on health-related quality of life, thus,
      there is a need for a specific instrument to assess AF symptoms and quality of
      life. METHODS: We developed and validated a specific questionnaire for quality of
      life in AF patients (QLAF) based on clinical manifestations (palpitation,
      breathlessness, dizziness and chest pain), and the usual treatments (medication,
      cardioversion and ablation). For validation, the new questionnaire was compared
      with the generic SF-36 questionnaire. Reproducibility was tested using 40
      questionnaires administered by two different observers at distinct times and
      places. Responsiveness was evaluated based on variation of the QLAF score over
      time. RESULTS: There were a total of 462 questionnaires (231 SF-36 and 231 QLAF)
      administered at baseline, 3, 6, 9 and 12 months. Construct validity was
      demonstrated by the negative correlation between QLAF and SF-36 scores that was
      observed over the follow-up period. Analysis of internal consistency for
      reproducibility showed excellent Cronbach's alpha coefficients (inter- and
      intraobserver coefficients of 0.98 and 0.96, respectively). QLAF was responsive
      as indicated by significant differences in mean domain scores from the beginning
      to the end of follow-up. It took much less time to administer the QLAF than the
      SF-36 (3:08+/-0:33 min vs. 9:25+/-1:14 min, p<0.001). CONCLUSION: The QLAF
      questionnaire is easy to understand and can be administered rapidly in the
      outpatient setting. Furthermore, the QLAF score is valid and reproducible and
      responsive to a change in clinical status.

PMID- 19395074
TI  - The chance finding at multislice computed tomography coronary angiography of an
      ectopic origin of the left circumflex coronary artery from the right sinus of
      Valsalva.
AB  - Anomalous coronary arteries occur in less than 2% of the general population. Most
      coronary anomalies are clinically asymptomatic. However some of them may present
      with chest pain, syncope, heart failure and sudden death. Acute myocardial
      infarction has been also described. Extravascular coronary compression results in
      dynamic obstruction which can cause effort angina as well as syncope and
      anomalous coronary arteries with an inter-arterial course are associated with
      sudden cardiac death. Anomalous origin of the circumflex coronary artery from the
      right sinus of Valsalva is thought to be of little clinical significance without
      the presence of severe narrowing of the vessel. Adequate visualization of the
      anomaly is essential for proper patient management. It has reported the full
      capability and accuracy of computed tomography coronary angiography in the
      identification and evaluation of the ectopic origin of the left circumflex
      coronary artery from the right sinus of Valsalva, displaying accurately the
      origin, size, course, and relationship of the anomalous vessel with respect to
      surrounding structures. We report a case of chance finding at multislice computed
      tomography coronary angiography of an ectopic origin of the left circumflex
      coronary artery from the right sinus of Valsalva. Also this case focuses
      attention on the anomalous origin of the circumflex coronary artery from the
      right sinus of Valsalva and confirms the full capability and accuracy of computed
      tomography coronary angiography in its adequate visualization.

PMID- 19395076
TI  - Assessment of two novel ventilatory surrogates for use in the delivery of
      gated/tracked radiotherapy for non-small cell lung cancer.
AB  - BACKGROUND: In selected patients with NSCLC the therapeutic index of radical
      radiotherapy can be improved with gating/tracking technology. Both techniques
      require real-time information on target location. This is often derived from a
      surrogate ventilatory signal. We assessed the correlation of two novel surrogate
      ventilatory signals with a spirometer-derived signal. The novel signals were
      obtained using the VisionRT stereoscopic camera system. The VisionRT-Tracked
      Point (VRT-TP) signal was derived from tracking a point located midway between
      the umbilicus and xiphisternum. The VisionRT-Surface-Derived-Volume (VRT-SDV)
      signal was derived from 3D body surface imaging of the torso. Both have potential
      advantages over the current surrogate signals. METHODS: Eleven subjects with
      NSCLC were recruited. Each was positioned as for radiotherapy treatment, and then
      instructed to breathe in five different modes: normal, abdominal, thoracic, deep
      and shallow breathing. Synchronous ventilatory signals were recorded for later
      analysis. The signals were analysed for correlation across all modes of
      breathing, and phase shifts. The VRT-SDV was also assessed for its ability to
      determine the mode of breathing. RESULTS: Both novel respiratory signals showed
      good correlation (r>0.80) with spirometry in 9 of 11 subjects. For all subjects
      the correlation with spirometry was better for the VRT-SDV signal than for the
      VRT-TP signal. Only one subject displayed a phase shift between the VisionRT
      derived signals and spirometry. The VRT-SDV signal could also differentiate
      between different modes of breathing. Unlike the spirometer-derived signal,
      neither VisionRT-derived signal was subject to drift. CONCLUSION: Both the VRT-TP
      and VRT-SDV signals have potential applications in ventilatory-gated and tracked
      radiotherapy. They can also be used as a signal for sorting 4DCT images, and to
      drive 4DCT single- and multiple-parameter motion models.

PMID- 19395075
TI  - Adolescents and asthma: why bother with our meds?
AB  - BACKGROUND: Adherence to inhaled steroid regimens for asthma is poor in adults
      and children. Although it is assumed that nonadherence contributes to morbidity
      in older adolescents, investigation is limited. OBJECTIVE: We sought to describe
      adherence to preventive asthma medications and explore relevant beliefs and
      attitudes in older urban adolescents, including their ideas for improving
      adherence. METHODS: Quantitative and qualitative methods were used to collect
      data from a convenience sample of adolescents with asthma previously prescribed
      fluticasone/salmeterol (F/S). Two semistructured face-to-face interviews were
      conducted 1 month apart and analyzed for themes. F/S use was electronically
      monitored between visits and calculated as the number of actuations divided by
      the number of inhalations prescribed. RESULTS: Forty participants, (15-18 years
      of age, 19 female subjects, 30 black/African American subjects, 11 Medicaid
      insured subjects, and 24 previously hospitalized for asthma) with a median FEV1
      of 98% of predicted value (range, 67% to 127%) had median adherence of 43%
      (range, 4% to 89%). Adherence was not associated with FEV1 or emergency
      department visits. Themes emerged from interviews as follows. Teens (1) take F/S
      inconsistently; (2) believe F/S is "supposed to help me breathe"; (3) dislike its
      taste; (4) are "too busy" and "forget"; and (5) recommend "reminder" solutions to
      poor adherence. Twenty percent believed that taking F/S was unnecessary, and
      another 18% expressed ambivalence about its benefits. CONCLUSION: Adherence was
      poor. Examining and acknowledging health beliefs of older teens in the context of
      their complicated lives might facilitate discussions about self-management.

PMID- 19395077
TI  - Multiple correlations of material parameters of light-cured dental composites.
AB  - OBJECTIVES: The aim of this study was to explore the correlations between the
      Knoop hardness, Young's modulus, viscosity, and polymerization shrinkage of an
      experimental dental composite, in order to determine the temporal variations of
      the material properties during the polymerization process. METHODS: The digital
      image correlation method was employed to measure the polymerization shrinkage
      along the curing depth of bar-shape specimens (cross-section 4mmx2mm and length
      10mm) of an experimental composite RZE045. The shrinkage data were correlated
      with the Knoop microhardness measured on specimens prepared in consistent
      conditions. Another series of tests were performed on cuboid composite samples
      (cross-section 4mmx4mm and height 5mm) with different degrees of conversions to
      determine the correlations among microhardness, Young's modulus and viscosity.
      Further correlations between shrinkage, Young's modulus and viscosity were then
      derived, from which the temporal variations of the mechanical parameters during
      curing were estimated. RESULTS: Along the curing depth, the Knoop microhardness
      of the experimental composite RZE045 decreased more rapidly than its volumetric
      shrinkage. A power function was employed to describe their relation. On the other
      hand, Knoop microhardness was found to be proportional to Young's modulus and
      viscosity. These linear correlations also seemed to be applicable to other
      materials including unfilled resins, silica glass and other dental composites.
      SIGNIFICANCE: Correlations between material parameters of dental composites
      allowed the rapid temporal variations of Young's modulus and viscosity during
      curing to be estimated based on the measured polymerization shrinkage-strain
      history.

PMID- 19395078
TI  - Fatigue testing of two porcelain-zirconia all-ceramic crown systems.
AB  - OBJECTIVE: To evaluate the mouth-motion step-stress fatigue behavior of two
      porcelain-zirconia all-ceramic crown systems. METHODS: The average dimensions of
      a mandibular first molar crown were imported into CAD software; a tooth
      preparation was modeled by reducing proximal walls by 1.5 mm and occlusal surface
      by 2.0 mm. The CAD-based tooth preparation was made by rapid prototyping and used
      as a master die to fabricate all-ceramic crowns with 1.0 mm porcelain veneered on
      0.5 mm Y-TZP cores (LAVA veneer+LAVA frame, 3M/ESPE, and Vita veneer+CERCON
      frame, Dentsply). Crowns were cemented on aged (60 days in water) composite
      (Z100, 3M/ESPE) reproductions of the die. Three crowns from the LAVA group were
      subjected to single cycle load to failure for stress profile design; remainder
      subjected to step-stress mouth-motion fatigue (three step-stress profiles). All
      mechanical testing was performed by sliding a WC indenter of 6.25 mm diameter 0.7
      mm lingually down the mesio-distal cusp. Master Weibull curves and reliability
      for missions of 50,000 cycles at 200 N load were calculated (Alta Pro 7,
      Reliasoft). RESULTS: Single load to failure showed fractures through the zirconia
      core. Reliability for a 200 N x 50K cycle mission was not significantly different
      between systems. In fatigue, failure occurred by formation of large chips within
      the veneer originating from the contact area without core exposure. CONCLUSIONS:
      LAVA and CERCON ceramic systems present similar fatigue behavior; fatigue loading
      of both systems reproduces clinically observed failure modes.

PMID- 19395079
TI  - Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind
      trial in Japanese individuals with impaired glucose tolerance.
AB  - BACKGROUND: The increased prevalence of type 2 diabetes mellitus is a major
      concern for health providers. We therefore assessed whether voglibose, an alpha
      glucosidase inhibitor, could prevent the development of type 2 diabetes in high
      risk Japanese individuals with impaired glucose tolerance. METHODS: 1780 eligible
      patients on a standard diet and taking regular exercise with impaired glucose
      tolerance were randomly assigned to oral voglibose 0.2 mg three times a day
      (n=897) or placebo (n=883) in a multicentre, double-blind, parallel group trial.
      Treatment was continued until participants developed type 2 diabetes (primary
      endpoint) or normoglycaemia (secondary endpoint), or for a minimum of 3 years,
      subject to the findings of an interim analysis. Analysis was by full analysis
      set. This trial is registered with the University Hospital Medical Information
      Network (UMIN) clinical trials registry, number UMIN 000001109. FINDINGS: In the
      interim analysis, voglibose was better than placebo (p=0.0026) in individuals
      treated for an average of 48.1 weeks (SD 36.3). Patients treated with voglibose
      had a lower risk of progression to type 2 diabetes than did those on placebo (50
      of 897 vs 106 of 881; hazard ratio 0.595, 95% CI 0.433-0.818; p=0.0014). More
      people in the voglibose group achieved normoglycaemia than did those in the
      placebo group (599 of 897 vs 454 of 881; 1.539, 1.357-1.746; p<0.0001). 810 (90%)
      of 897 patients in the voglibose group had adverse events versus 750 (85%) of 881
      in the placebo group. Serious adverse events (all one each) in the voglibose
      group were cholecystitis, colonic polyp, rectal neoplasm, inguinal hernia, liver
      dysfunction, and subarachnoid haemorrhage, and in the placebo group were cerebral
      infarction and cholecystitis. INTERPRETATION: Voglibose, in addition to lifestyle
      modification, can reduce the development of type 2 diabetes in high-risk Japanese
      individuals with impaired glucose tolerance. FUNDING: Takeda.

PMID- 19395080
TI  - Voglibose for prevention of type 2 diabetes mellitus.

PMID- 19395081
TI  - Different mercury bioaccumulation kinetics by two macrobenthic species: the
      bivalve Scrobicularia plana and the polychaete Hediste diversicolor.
AB  - Mercury is a global priority pollutant and given its huge relevance in terms of
      environmental damage and a threat to human health, it is important to study the
      bioaccumulation processes at the level of macrobenthic organisms and evaluate
      possible consequences for the trophic chain. In this work we evaluate the mercury
      accumulation rates of two distinct and economically important macrobenthic
      species, the polychaete Hediste diversicolor and the bivalve Scrobicularia plana,
      through a mesocosms laboratory experiment. The present experiment demonstrated
      different bioaccumulation kinetics for each species: while S. plana has a rapid
      accumulation after 48 h of exposure to contaminated sediments and then reaches a
      steady state, H. diversicolor has a linear mercury accumulation throughout the
      experiment time (31 days). The different patterns observed can be related to
      different feeding strategies and assimilation efficiencies. In addition, we can
      conclude that independently of the mercury concentration in the sediments, the
      two studied species in both contaminated sediments reached the same percentage
      (25%) of mercury accumulated at the end of the experiment when compared to the
      maximum concentrations recorded in the field. This experiment highlights that the
      mercury bioaccumulation rate by these two economically and ecologically important
      macrobenthic species is a reasonably rapid process which can promote serious
      consequences for the higher trophic levels, constituting a severe risk to the
      natural environment and ultimately to human health.

PMID- 19395082
TI  - Superparamagnetic iron oxide nanoparticle-embedded encapsulated microbubbles as
      dual contrast agents of magnetic resonance and ultrasound imaging.
AB  - An encapsulated microbubble (EMB) of a novel construct is proposed to enhance the
      magnetic resonance imaging contrast by introducing superparamagnetic iron oxide
      (SPIO) nanoparticles (mean diameter is 12 nm) into the polymer shell of the
      microbubble. Such microbubble vesicle has nitrogen gas in the core and its mean
      diameter is 3.98 microm. An in vitro MR susceptibility experiment using a phantom
      consisting EMBs has shown that the relationship between the transverse relaxation
      rate R(2) and the Fe(3)O(4) nanoparticle concentration in the shell (the volume
      fraction of EMBs is kept constant) can be fitted to a linear function and an
      exponentially growth function is observed between R(2) and the SPIO-inclusion
      microbubble concentration. The in vivo MRI experiments also show that the SPIO
      inclusion microbubbles have longer contrast-enhancement duration time in rat
      liver than non-SPIO-inclusion microbubbles. An in vitro ultrasound imaging
      experiment of SPIO-inclusion microbubbles also shows that they can enhance the
      ultrasound contrast significantly. Additionally, the interaction between the SPIO
      inclusion microbubbles and cells indicates that such microbubble construct can
      retain the acoustic property under the ultrasound exposure by controlling the
      SPIO concentration in the shell. Therefore, the proposed SPIO nanoparticle
      embedded EMBs potentially can become effective MR susceptibility contrast agents
      while also can be good US contrast agents.

PMID- 19395083
TI  - Intraperitoneal administration of shiga toxin type 2 in rats in the late stage of
      pregnancy produces premature delivery of dead fetuses.
AB  - Infection associated with Shiga toxin-producing Escherichia coli (STEC) and
      subsequent Hemolytic-Uremic Syndrome (HUS) have become relevant in public health
      since STEC is considered as one of the most important emergent pathogens. STEC
      infection may either be asymptomatic or begin with watery diarrhea associated
      with hemorrhagic colitis and HUS. The major virulence factor of STEC is Shiga
      toxin type 1 or 2 (Stx1, Stx2) although strains that express only Stx2 are highly
      prevalent. Up to now, it has not been established whether STEC infection affect
      pregnant women. In this study, we evaluated the effect of Stx2 on maternal
      lethality, fetal status and delivery time by injecting Stx2 in rats in the late
      stage of pregnancy. Stx2 induced fetal resorption, placental abruption,
      intrauterine hemorrhage and fetal death at 1-2 days post-injection in a dose
      dependent manner. With 2ng Stx2/g body weight, placentas and fetuses presented
      extensive necrotic areas, while uteri and kidneys showed normal histology.
      Immunolocalization of Stx2 was observed in placentas and fetuses. With 4 and 6ng
      Stx2/g body weight maternal death was also observed. Those rats that survived
      after Stx2-treatment were able to become pregnant and deliver normal pups at
      term. Our results show, for the first time, that the preterm labor with fetal
      death observed in treated rats may be a consequence of the action of Stx2 on the
      feto-maternal unit. Although there are no reports of Stx2 effects in human
      pregnancy, we speculate that STEC infections could be one of the causes not yet
      determined of fetal morbimortality.

PMID- 19395085
TI  - Human milk biomonitoring of phthalates: expanding our understanding of infant
      exposure is compatible with supporting breastfeeding.

PMID- 19395084
TI  - Regulation of Ca2+ entry by inositol lipids in mammalian cells by multiple
      mechanisms.
AB  - Increased phosphoinositide turnover was first identified as an early signal
      transduction event initiated by cell surface receptors that were linked to
      calcium signaling. Subsequently, the generation of inositol 1,4,5-trisphosphate
      by phosphoinositide-specific phospholipase C enzymes was defined as the major
      link between inositide turnover and the cytosolic Ca(2+) rise in response to
      external stimulation. However, in the last decades, phosphoinositides have been
      emerging as major regulatory lipids involved in virtually every membrane
      associated signaling process. Phosphoinositides regulate both the activity and
      the trafficking of almost all ion channels and transporters contributing to the
      maintenance of the ionic gradients that are essential for the proper functioning
      of all eukaryotic cells. Here we summarize the various means by which
      phosphoinositides affect ion channel functions with special emphasis on Ca(2+)
      signaling and outline the principles that govern the highly compartmentalized
      roles of these regulatory lipids.

PMID- 19395086
TI  - Comparison of retinal nerve fiber layer measurements using time domain and
      spectral domain optical coherent tomography.
AB  - PURPOSE: To determine the agreement between peripapillary retinal nerve fiber
      layer (RNFL) thickness measurements from Stratus time domain optical coherence
      tomography (OCT) and Cirrus spectral domain OCT (Carl Zeiss Meditec, Dublin, CA)
      in normal subjects and subjects with glaucoma. DESIGN: Evaluation of diagnostic
      test or technology. PARTICIPANTS: A total of 130 eyes from 130 normal subjects
      and subjects with glaucoma were analyzed. The subjects were divided into groups
      by visual field criteria: normal (n = 29), glaucoma suspect (n = 12), mild
      glaucoma (n = 41), moderate glaucoma (n = 18), and severe glaucoma (n = 30).
      METHODS: Peripapillary RNFL thickness was measured with Stratus Fast RNFL and
      Cirrus 200 x 200 Optic Disc Scan on the same day in 1 eye of each subject to
      determine agreement. Two operators used the same instruments for all scans. MAIN
      OUTCOME MEASURES: Student paired t testing, Pearson's correlation coefficient,
      and Bland-Altman analysis of RNFL thickness measurements. RESULTS: The average
      age of the glaucoma group was significantly more than that of the normal group:
      68.3+/-12.3 years versus 55.7+/-12.1 years, respectively. For Stratus OCT, the
      average RNFL thickness (mean +/- standard deviation) was 99.4+/-13.2 microm,
      94.5+/-15.0 microm, 79.0+/-14.5 microm, 62.7+/-10.2 microm, and 51.0+/-8.9 microm
      for the normal, suspect, mild, moderate, and severe groups, respectively. For
      Cirrus OCT, the corresponding measurements were 92.0+/-10.8 microm, 88.1+/-13.5
      microm, 73.3+/-11.8 microm, 60.9+/-8.3 microm, and 55.3+/-6.6 microm. All Stratus
      Cirrus differences were statistically significant by paired t testing (P<0.001)
      except for the moderate group (P = 0.11). For average RNFL, there was also a
      highly significant linear relationship between Stratus minus Cirrus difference
      and RNFL thickness (P<0.001). Bland-Altman plots showed that the systematic
      difference of Stratus measurements are smaller than Cirrus at thinner RNFL values
      but larger at thicker RNFL values. CONCLUSIONS: RNFL thickness measurements
      between Stratus OCT and Cirrus OCT cannot be directly compared. Clinicians should
      be aware that measurements are generally higher with Stratus than with Cirrus
      except when the RNFL is very thin, as in severe glaucoma. This difference must be
      taken into account if comparing Stratus measurements with Cirrus measurements.

PMID- 19395087
TI  - Birth weight and optic nerve head parameters.
AB  - PURPOSE: To assess the relationship of birth weight, birth length, and head
      circumference as proxy markers of intrauterine growth, cup/disc ratio, and other
      optic disc parameters measured using optical coherence tomography (OCT). DESIGN:
      Population-based cross sectional analysis. PARTICIPANTS: The Sydney Childhood Eye
      Study examined 2353 primarily 12-year-old children from 21 randomly selected
      secondary schools during 2003 to 2005. METHODS: Of 2353 children examined, 2134
      (90.7%) had OCT scans (Zeiss Stratus OCT, Carl Zeiss Meditec, Dublin, CA) and are
      included in this study. The "fast" optic disc scan protocol was used. Birth
      weight, birth length, and head circumference were ascertained from health
      records. Height and weight were measured using standardized protocols, body mass
      index (BMI) was defined as weight (kilograms)/ height squared (meters), and
      sociodemographic information was collected in a questionnaire completed by
      parents. Low birth weight was defined as birth weight <or=2499 g, and prematurity
      was defined as gestation less than 37 weeks. Logistic and mixed model analyses
      were performed. MAIN OUTCOME MEASURES: Vertical optic disc and optic cup
      diameters, and cup/disc ratio. RESULTS: Children of low birth weight had
      decreased vertical disc diameter, increased cup diameter, and increased cup/disc
      ratio by 30 microm (P = 0.009), 44 microm (P = 0.004), and 0.03 (P<0.0001),
      respectively. After adjusting for age, gender, ethnicity, height, axial length,
      and BMI, birth weight remained positively associated with vertical optic disc
      diameter and inversely associated with both vertical optic cup diameter and
      vertical cup/disc ratio (each kilogram increase was associated with a 0.0133-mm
      larger mean disc diameter; P = 0.04; a 0.0203-mm smaller mean cup diameter; P =
      0.02; and a 0.0136 reduction in mean cup/disc ratio; P = 0.002). These
      associations were not present in children with gestational age less than 33
      weeks. Smaller birth length and head circumference were similarly associated with
      larger cup/disc ratio. CONCLUSIONS: Low birth weight, short birth length, and
      small head circumference at birth were associated with larger cup/disc ratio in
      children aged 12 years. Our findings suggest that fetal growth restriction could
      adversely influence optic nerve head parameters. This may have implications for
      future risk of glaucomatous optic neuropathy. FINANCIAL DISCLOSURE(S): The
      author(s) have no proprietary or commercial interest in any materials discussed
      in this article.

PMID- 19395088
TI  - Immunoactivation in preeclampsia: Vdelta2+ and regulatory T cells during the
      inflammatory stage of disease.
AB  - Recent data suggest a dominant role of the innate, rather than the adaptive
      immune system in pregnancy-related immunoregulation. gamma/delta T cells, that
      comprise a minor subpopulation of human peripheral blood lymphocytes, represent a
      link between the innate and the acquired immune systems. However little is known
      about how they function in preeclampsia, which is suggested to be associated with
      a Th1 predominant immune response. The aim of our study was to investigate the
      presence and phenotype of Vdelta2+ cells and of regulatory T cells in the
      pathogenesis of preeclampsia. Since Vdelta2+ T cell function has been shown to be
      altered in patients with preeclampsia we investigated the expression of perforin,
      Fas and TIM-3 by Vdelta2+ T cells and the possible role of activating and
      inhibitory NK cell receptors as well as of regulatory T cells. Vdelta2+ T cells
      of preeclamptic patients demonstrated an increased perforin and IFNgamma
      production, which could be explained by dysregulation of NK cell receptor
      expression. These Th1 polarized cells were less susceptible to apoptosis than
      Vdelta2+ T cells from healthy pregnant women. Our data suggest that activated
      Vdelta2+ T cells of preeclamptic women have an increased cytotoxic potential,
      which may be due to altered expression of NK cell inhibitory and activating
      receptors. In this study we report a series of observations, which taken together
      suggest the role of multiple pathways in generating an exaggerated systemic
      inflammatory response observed in the clinical stage of preeclampsia.

PMID- 19395089
TI  - Conception season and cerebral asymmetries among American baseball players:
      implications for the seasonal birth effect in schizophrenia.
AB  - People with schizophrenia and children born with neural tube defects both tend to
      be conceived most often in May-June, about a month before the summer solstice,
      and least often in November-December, a month before the winter solstice. Such
      timings, coupled with evidence of cerebral asymmetry deficits in schizophrenia,
      and evidence that asymmetry development and neural tube closure represent
      concurrent fourth-embryonic-week processes both sensitive to oxidant stress, led
      us to the hypothesis that pro-oxidant sunlight actions capable of affecting the
      mother's blood could result in a peri-June peak of inhibition and a peri-December
      peak of facilitation of both processes. Here, using birth and hand preference
      data from baseball statistics, we tested the hypothesis's prediction that, as a
      group representing minimal cerebral lateralization, left-handed players would
      show the same conception rhythm as that observed in the above disorders. We found
      that not only strict left-handers (those both batting and throwing left) were
      most often conceived in May-June but that also strict right-handers and other
      players denoting more extreme levels of cerebral lateralization were most often
      conceived in November-December.

PMID- 19395090
TI  - In vitro modulatory effect of omega-3 polyunsaturated fatty acid (EPA and DHA) on
      phagocytosis and ROS production of goat neutrophils.
AB  - An in vitro study was carried out to examine the influence of two fish-oil
      derived long chain omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA), on goat polymorphonuclear leukocytes
      (PMN). Twelve Saanen healthy goats were used as blood donors. Neutrophils were
      isolated from blood and incubated with increasing concentration of EPA and DHA
      (25, 50, 100, 200muM). Control samples were incubated in the absence of omega-3
      PUFAs. Phagocytosis was evaluated by fluorescein-labeled Escherichia coli
      incorporation, while extracellular Reactive Oxygen Species (ROS) production was
      determined by cytochrome c reduction assay, which was selected among the others
      due to its specificity for extracellular superoxide anion release. Phagocytic
      activity was significantly increased by EPA (P<0.05) and DHA (P<0.01). Treating
      PMN with EPA does not affect extracellular ROS production which is, on the
      contrary, down-regulated by DHA. This effect was increased in experimental
      conditions which mimic pro-inflammatory challenges (stimulation with PMA). This
      study demonstrates that EPA and DHA may have beneficial effect on neutrophil
      function by increasing their phagocytosis activity and, in the meanwhile,
      decreasing the tissue damages due to extracellular release of ROS.

PMID- 19395091
TI  - Differences in metal sequestration between zebra mussels from clean and polluted
      field locations.
AB  - Organisms are able to detoxify accumulated metals by, e.g. binding them to
      metallothionein (MT) and/or sequestering them in metal-rich granules (MRG). The
      different factors involved in determining the capacity or efficiency with which
      metals are detoxified are not yet known. In this work we studied how the sub
      cellular distribution pattern of cadmium, copper and zinc in whole tissue of
      zebra mussels from clean and polluted surface waters is influenced by the total
      accumulated metal concentration and by its physiological condition. Additionally
      we measured the metallothionein concentration in the mussel tissue. Metal
      concentration increased gradually in the metal-sensitive and detoxified sub
      cellular fractions with increasing whole tissue concentrations. However, metal
      concentrations in the sensitive fractions did not increase to the same extent as
      metal concentrations in whole tissues. In more polluted mussels the contribution
      of MRG and MT became more important. Nevertheless, metal detoxification was not
      sufficient to prevent metal binding to heat-sensitive low molecular weight
      proteins (HDP fraction). Finally we found an indication that metal detoxification
      was influenced by the condition of the zebra mussels. MT content could be
      explained for up to 83% by variations in Zn concentration and physiological
      condition of the mussels.

PMID- 19395092
TI  - Changing axis deviation during atrial fibrillation.

PMID- 19395093
TI  - Acute efficacy of combined therapy of carperitide and nicorandil for acute
      decompensated heart failure with left ventricular systolic dysfunction.
AB  - A 64-year-old woman was admitted to our hospital with acute decompensated heart
      failure (ADHF) and left ventricular systolic dysfunction. Initial treatment with
      carperitide (0.01 ug/kg/min) had little effect. Since she had a borderline
      systolic blood pressure (i.e., a systolic BP between 90 and 110 mm Hg) and atrial
      fibrillation with a rapid ventricular response, nicorandil (0.1 mg/kg/h) was
      added to carperitide. This combined therapy achieved rapid improvement of ADHF.
      To our knowledge, this is the first report of a patient with ADHF and borderline
      systolic blood pressure in whom the combination of carperitide and nicorandil was
      safe and effective.

PMID- 19395094
TI  - Kounis syndrome in a patient with ovarian cancer and allergy to iodinated
      contrast media: report of a case of vasospastic angina induced by chemotherapy.
AB  - We report the case of a 71-year-old woman with previous coronary angioplasty,
      ovarian cancer with multiple metastases and allergy to iodinated contrast media,
      who developed vasospastic angina after several treatments with cisplatin and
      cyclophosphamide, so that we considered this as a case of "allergic angina" or
      Kounis syndrome (type II variant). The patient underwent standard anti-ischemic
      therapy with nitrates, calcium blocking agents and enoxaparin so having an
      uneventful outcome.

PMID- 19395095
TI  - Effect of atorvastatin on cardiac remodelling and mortality in rats following
      hyperglycemia and myocardial infarction.
AB  - Effect of HMGCoA Reductase Inhibitors on Cardiac Remodelling and Mortality in
      Rats. Following Hyperglycemia and Myocardial Infarction. AIMS: The presence of
      diabetes mellitus (DM) in patients with myocardial infarction (MI) increases
      mortality, due in part to the presence of known cardiovascular risk factors.
      However little is known about the impact of DM on cardiac remodelling and on
      clinical outcomes. We aimed to investigate whether hyperglycaemia may adversely
      and additionally affect LV remodelling post-MI, and whether the addition of a
      statin, known to reduce mortality both post MI and in humans with DM, has an
      effect on these outcomes. METHODS: Eight week old Sprague-Dawley rats were
      allocated to 5 groups--control (non-DM)/sham, control-MI, DM-sham, DM-MI and DM
      MI with statin gavage (DM-MI/ATV). Echocardiogram and invasive pressure volume
      analysis were performed prior to sacrifice for estimation of cardiac function.
      Tissue was analysed for total cardiac collagen, collagen I and III. RESULTS:
      Hyperglycaemia in the remodelling period significantly increased mortality (70%
      survival in the C-MI group vs 27% in the DM-MI group), worsened cardiac function
      and increased fibrosis. All of these variables were attenuated by the addition of
      a statin. CONCLUSION: Hyperglycaemia increased mortality in MI and exacerbated LV
      remodeling, and this was attenuated with statin use. This study confirms the
      importance of early and intensive treatment of hyperglycaemia in patients with MI
      and suggests that in humans with both DM and MI the addition of a statin may be
      beneficial.

PMID- 19395096
TI  - Gonadal and adrenal androgen deficiencies as independent predictors of increased
      cardiovascular mortality in men with type II diabetes mellitus and stable
      coronary artery disease.
AB  - BACKGROUND: Age-related decline in circulating androgens in men is associated
      with poor cardiovascular (CV) outcome. Men with type II diabetes mellitus (DM)
      are prone to develop androgen deficiency. OBJECTIVES: We studied the prevalence
      and prognostic consequences of deficiencies in circulating total and free
      testosterone (TT, FT) and dehydroepiandrosterone sulphate (DHEAS) in type II DM
      men with coronary artery disease (CAD). METHODS: We examined 153 diabetic men
      with stable CAD (age: 65+/-9 years). Serum levels of FT were estimated (eFT) from
      TT and sex hormone binding globulin levels. RESULTS: TT, eFT and DHEAS
      deficiencies (serum levels<=the 10th percentile of healthy peers) were found in
      22%, 33% and 77% of DM men with CAD, being more frequent than in healthy peers
      (all p<0.001). During follow-up (median: 19 months), there were 43 (28%) CV
      deaths. We identified 4 independent predictors of CV mortality: testosterone (TT,
      eFT) and DHEAS deficiencies, high plasma N-terminal pro-B-type natriuretic
      peptide (>=2661 pg/mL, upper quartile), high serum high sensitivity C-reactive
      protein (>=6.58 mg/L, upper quartile) (all p<0.01). There was a graded relation
      between the number of risk factors and increased CV mortality: hazard risk (95%
      confidence interval) for 1, 2, 3-4 vs. no risk factors, respectively: 5.9 (0.8
      45.6), p=0.09, 9.2 (1.2-69.2), 63.0 (8.0-498.7), p<0.0001 (chi(2)=42.23,
      p<0.0001). CONCLUSIONS: In diabetic men with stable CAD, testosterone and DHEAS
      deficiencies are common and related to high CV mortality. Whether an androgen
      substitution would improve prognosis in androgen deficient men with type II
      diabetes and stable CAD, requires further studies.

PMID- 19395098
TI  - Ventricular dysfunction in type 1 myotonic dystrophy: electrical, mechanical, or
      both?
AB  - BACKGROUND: Myotonic dystrophy type 1 (DM1) is a systemic disease which affects
      the heart and may be a cause of sudden death. Conduction disturbances are the
      major cardiac abnormalities seen in this condition. We sought to assess
      electrical and mechanical cardiac functions to identify abnormalities that might
      explain sudden cardiac death in DM1. METHODS: Thirty six patients with DM1 and 16
      controls were studied using echocardiography including myocardial Doppler. ECG
      recordings were also obtained. RESULTS: Left ventricular (LV) dimensions were
      maintained but systolic function was reduced (p<0.001), including stroke volume
      (p<0.05). LV segmental myocardial isovolumic contraction time was prolonged
      (p<0.001) and correlated with PR interval (p<0.001). Isovolumic relaxation time
      was prolonged (p<0.05) and filling time was reduced (p<0.001). LV cavity was
      significantly asynchronous demonstrated by prolonged total isovolumic time (t
      IVT) (p<0.001), high Tei index (p<0.001) and low ejection index (p<0.001). Right
      ventricular (RV) strain was reduced (p<0.001) as were its systolic and diastolic
      velocities (p<0.05 for both). 22/36 patients had prolonged LV t-IVT>12.3 s/min
      (upper 95% normal CI), 13 of whom had PR>=200 ms, 11 had QRS duration>120 ms (5
      had combined abnormality) and the remaining 5 had neither. Over the 3 years
      follow up 10 patients had events, 6 of them cardiac. t-IVT was prolonged in 5/6
      patients, PR interval in 4 and QRS duration in one. CONCLUSIONS: In DM1 patients,
      LV conventional measurements are modestly impaired but cardiac time relations
      suggest marked asynchronous cavity function. Although our findings were primarily
      explained on the basis of long PR interval or broad QRS duration a minority
      presented an evidence for myocardial cause of asynchrony rather than electrical.
      Early identification of such abnormalities may guide towards a need for
      additional electrical resynchronization therapy which may improve survival in a
      way similar to what has been shown in heart failure trials.

PMID- 19395099
TI  - Regional prevalence and clinical benefit of implantable cardioverter
      defibrillators in Brugada syndrome.
AB  - BACKGROUND: Brugada syndrome (BS) is associated with an increased risk of sudden
      cardiac death (SCD) caused by ventricular tachyarrhythmia. Thus, implantable
      cardioverter defibrillators (ICD) became the main therapeutic option in these
      patients. We aimed to investigate the prevalence of BS in the Eastern Alps as
      well as the benefit of ICD therapy in this collective. METHODS: During physical
      examination before military service, 47,606 Austrian men were screened for
      Brugada ECG pattern. Furthermore, we followed 4491 patients with arrhythmia
      during the last two decades, of which 26 patients (20 male; age at diagnosis:
      43.2 +/- 11.6 years) revealed BS. Diagnosis was based on characteristic ECG
      either at rest (11 patients) or after provocation with Ajmaline (15 patients).
      RESULTS: The nationwide screening revealed one individual with Brugada ECG
      (prevalence of 2.10/100,000 inhabitants). Prior to diagnosis of BS, syncope and
      SCD survival were observed in 7 and 4 patients, respectively; the remaining 15
      patients were asymptomatic. ICD were implanted in 17 patients (15 male). Three
      asymptomatic patients received no ICD because no tachyarrhythmia was inducible on
      programmed stimulation. Six asymptomatic patients without family history of
      sudden death refused further evaluation. Mean ICD follow-up period was 57.0 +/-
      32.2 months. Two patients (11.7%) needed defibrillation therapy. Four patients
      (23.5%) received exclusively inappropriate shocks (three due to T-wave
      oversensing, one due to atrial fibrillation). CONCLUSIONS: Brugada syndrome has a
      low prevalence in the Eastern alpine region. Patients with BS benefit from ICD
      implantation, but less frequently than anticipated. The problem of inappropriate
      ICD discharges is still of major concern.

PMID- 19395100
TI  - The chance finding at multislice computed tomography coronary angiography of
      myocardial bridging.
AB  - Myocardial bridging is present when a segment of a major epicardial coronary
      artery, the 'tunnelled artery', runs intramurally through the myocardium. With
      each systole, the coronary artery is compressed. The pathophysiology of
      myocardial bridging is incompletely understood. With each systole, the coronary
      artery is compressed. Moreover, intravascular ultrasound analysis revealed a
      delayed relaxation after systolic compression, which may extend significantly
      into diastole. This explains both the impaired coronary flow reserve and
      ischemia. Evidence indicates that the intima beneath the bridge is protected from
      atherosclerosis, and the proximal segment is more susceptible to the development
      of atherosclerotic lesions because of haemodynamic disturbances. Myocardial
      bridging is sometimes associated with overt pathology, as well as it can just be
      an incidental finding without any significance. Myocardial bridging may cause
      angina pectoris, myocardial infarction, life threatening arrhythmias and even
      sudden cardiac death but most of them are harmless. Furthermore depressed left
      ventricular function, myocardial stunning, early death after cardiac
      transplantation has been also reported. Although the exact management is not well
      known, beta blockers seem to be the first choice. Stenting is controversial and
      one must think "twice" before stenting the bridged coronary artery. We report a
      case of chance finding at multislice computed tomography coronary angiography of
      two myocardial bridging. Also this case focuses attention on myocardial bridging
      and it confirms that multislice computed tomography coronary angiography
      technology represents a useful, noninvasive imaging method of its assessment.

PMID- 19395101
TI  - Tetralogy of Fallot associated with right arch and persistent left dorsal aortic
      aneurysm.
AB  - We described a patient who was diagnosed of Tetralogy of Fallot with right arch.
      Dorsal aortic aneurysm was found later confirmed by cardiac catheterization and
      reconstruction of 3D computer tomography. To our knowledge, the combination of
      Tetralogy of Fallot and dorsal aortic aneurysm had never been reported.

PMID- 19395103
TI  - The effect of reimbursement on medical decision making: do physicians alter
      treatment in response to a managed care incentive?
AB  - The empirical literature that explores whether physicians respond to financial
      incentives has not definitively answered the question of whether physicians alter
      their treatment behavior at the margin. Previous research has not been able to
      distinguish that part of a physician response that uniformly alters treatment of
      all patients under a physician's care from that which affects some, but not all
      of a physician's patients. To explore physicians' marginal responses to financial
      incentives while accounting for the selection of physicians into different
      financial arrangements where others could not, I use data from a survey of
      physician visits to isolate the effect that capitation, a form of reimbursement
      wherein physicians receive zero marginal revenue for a range of physician
      provided services, has on the care provided by a physician. Fixed effects
      regression results reveal that physicians spend less time with their capitated
      patients than with their non-capitated patients.

PMID- 19395102
TI  - Comparison of PPARdelta and PPARgamma in inhibiting the pro-inflammatory effects
      of C-reactive protein in endothelial cells.
AB  - BACKGROUND: Inflammation associated with endothelial cell dysfunction is a key
      step of atherogenesis. C-reactive protein (CRP), used to serve as a nonspecific
      clinical inflammation marker, has now emerged as a new marker for cardiovascular
      diseases. Recently, PPARdelta has revealed benefits for dealing with
      inflammation. The relationship between CRP-induced inflammation and PPARdelta
      agonist remains unclear. METHODS: Human umbilical vein endothelial cells (HUVECs)
      were separated into the following groups: 25 MUg CRP alone for 15 hours; CRP
      treated with 1 MUM PPARdelta(L-165041) or 10 MUM PPARgamma(troglitazone)
      agonists, and untreated HUVECs. This research focused on the CRP underlying
      signaling pathways and the effects of PPAR agonists on monocyte attachment to
      endothelial cells. RESULTS: Levels of interleukin-6 (IL-6) and IL-8 increased by
      CRP were both significantly attenuated by pretreatment with PPARdelta or
      PPARgamma agonists, but the needed dose of PPARdelta to reach the same effect was
      less than PPARgamma agonist. After incubation with CRP, immunoblotting showed a
      significant increase in NF-kappaB activation and CD32 receptor. These changes
      were associated with a significant increase of MCP-1 and VCAM-1 expression.
      PPARdelta treatment not only decreased these pro-inflammatory effects in HUVECs
      but also significantly attenuated monocyte adhesion to endothelial cells in less
      dosage than PPARgamma. CONCLUSIONS: The results suggest that PPARdelta attenuated
      CRP-induced pro-inflammatory effects may through CD32 and NF-kappaB pathway.
      PPARdelta may serve as a more potent therapeutic target than PPARgamma in
      atherosclerosis or inflammatory therapy.

PMID- 19395104
TI  - The complexity of cellular dedifferentiation: implications for regenerative
      medicine.
AB  - Cellular dedifferentiation underlies topical issues in biology, such as
      regeneration and somatic cell nuclear transfer (SCNT), and signifies the
      withdrawal of cells from a given differentiated state into a 'stem cell'-like
      state that confers pluripotency. Recently, there has been growing interest in
      exploiting the dedifferentiation process to obtain autologous stem cell lineages
      for use in regenerative medicine. This approach holds great promise, particularly
      in view of the ethical concerns invoked over the use of human embryonic stem
      cells in research and the problem of transplant rejection. However, new insights
      provided by the study of this process in plants and animals have highlighted the
      complexity and hazards of cellular dedifferentiation.

PMID- 19395105
TI  - An international review of patient safety measures in radiotherapy practice.
AB  - Errors from radiotherapy machine or software malfunction usually are well
      documented as they affect hundreds of patients, whereas random errors affecting
      individual patients are more difficult to be discovered and prevented. Although
      major clinical radiotherapy incidents have been reported, many more have remained
      unrecognised or have not been reported. The literature in this field is limited
      as it is mostly published as a result of investigation of major errors. We
      present a review of radiotherapy incidents internationally with the aim of
      identifying the domains where most errors occur through extensive review and
      synthesis of published reports, unpublished 'Grey literature' and departmental
      incident data. Our review of radiotherapy-related events in the last three
      decades (1976-2007) identified more than seven thousand (N=7741) incidents and
      near misses. Three thousand one hundred and twenty-five incidents reported
      patient harm of variable intensity ranging from underdose increasing the risk of
      recurrence, to overdose causing toxicity, and even death for 1% (N=38); 4616
      events were near misses with no recognisable patient harm. Based on our review, a
      radiotherapy risk profile has been published by the WHO World Alliance for
      Patient Safety that highlights the role of communication, training and strict
      adherence to guidelines/protocols in improving the safety of radiotherapy
      process.

PMID- 19395106
TI  - Visual and tactile action effects determine bimanual coordination performance.
AB  - Effect-based models of motor control assign a crucial role to anticipated
      perceptual feedback in action planning. Two experiments were conducted to test
      the validity of this proposal for discrete bimanual key press responses. The
      results revealed that the normally observed performance advantage for the
      preparation of two responses with homologous rather than non-homologous fingers
      becomes inverted when homologous fingers produce non-identical visual effects,
      and non-homologous fingers produce identical visual effects. In the second
      experiment the finger homology effect was strongly reduced when homologous
      fingers produced non-identical tactile feedback. The results show that
      representations of to-be-produced visual and tactile action effects both
      contribute to action planning, though possibly to a varying degree. Implications
      of these results for effect-based models of motor control are considered.

PMID- 19395107
TI  - Increased rate of force development of elbow flexors by antagonist conditioning
      contraction.
AB  - The effects of isometric antagonist conditioning contraction (ACC) at various
      durations and intensities on the contractile force, electromyographic (EMG)
      amplitude, and their rates of rise of elbow flexor muscles were examined in
      healthy participants. In particular, we focused on the change in the maximum rate
      of initial force development of agonists (dFagonist/dt(max)), which was evaluated
      by subtracting antagonist force decaying from apparent initial force development.
      While the ACC caused no statistically significant effect on the average force
      during elbow flexion, dFagonist/dt(max) was significantly increased by the ACC of
      short durations (1-2s) and large intensities. Similarly, the ACC did not affect
      the root mean square EMG amplitude of biceps brachii during elbow flexion, but
      significantly increased the maximum rate of rise of the absolute EMG amplitude
      (dE/dt(max)). These results suggested that facilitating effects of the ACC could
      be observed in the initial phase of agonist action in healthy participants, and
      ACC of shorter durations might be more effective. The increased dE/dt(max)
      suggested that increased neural activities might contribute to the antagonist
      conditioned facilitation of force development.

PMID- 19395108
TI  - Alcohol consumption and handwriting: a kinematic analysis.
AB  - Cerebellar dysfunction is associated with deficits in the control of movement
      extent, as well as changes in the amplitude and relative amounts of acceleration
      and deceleration and action tremor. The present study sought to identify whether
      cerebellar symptoms occur in the handwriting of intoxicated individuals. Twenty
      participants in two sub-groups (alcohol dependent and non-alcohol dependent) were
      asked to write four cursive letter 'l's on a Wacom SD420 graphics tablet before
      and after consumption of a dose of vodka and orange producing a peak blood
      alcohol concentration of 0.048%. There was a relationship between blood alcohol
      concentration and stroke length. Kinematic analysis of handwriting indicated
      increases in the relative proportions of time spent in acceleration and increases
      in spectral power around 4Hz. It was found that alcohol intoxication causes
      symptoms of cerebellar dysfunction, and that alcohol dependent individuals had
      less ballistic handwriting compared to non-alcohol dependent participants.

PMID- 19395109
TI  - A kinematic and dynamic comparison of surface and underwater displacement in high
      level monofin swimming.
AB  - Fin swimming performance can be divided into underwater and surface water races.
      World records are about 10% faster for underwater swimming vs. surface swimming,
      but little is known about the advantage of underwater swimming for monofin
      swimming. Some authors reported that the air-water interface influences the
      kinematics and leads to a narrow vertical amplitude of the fin. On the one hand,
      surface swimming is expected to affect drag parameters (cross-sectional area (S)
      and active drag (AD)) when compared to underwater swimming. On the other hand,
      the surface swimming technique may also affect efficiency (eta(F)). The aim of
      this study is therefore to evaluate and compare drag parameters and efficiency
      during underwater and surface swimming. To this end, 12 international level
      monofin swimmers were measured during both underwater and surface swimming.
      Kinematic parameters (both dimensional and non-dimensional), eta(F) (calculated
      according to the Elongated-Body Theory), and AD (computed with Velocity
      Perturbation Method) were calculated for an underwater and a surface fin swimming
      trial, performed at maximal speed. As expected, results showed significantly
      lower velocities during surface swimming vs. underwater V(1,under) =2.5ms(-1) vs.
      V(1,surf) =2.36ms(-1), p<.01). Velocities during underwater and surface swimming
      were strongly correlated (r=.97, p<.01). Underwater swimming was also associated
      with higher vertical amplitudes of the fin compared to surface swimming (V(under)
      =0.55mvs. V(surf) )=0.46m, p<.01). Length-specific amplitudes (A(under)/L(b))
      were in the order of 20% during underwater swimming as for undulating fish, and
      significantly higher than during surface swimming (A(surf)/L(b)=17%, p<.01).
      Efficiency for surface swimming was about 6% lower than for underwater swimming
      (eta(F,under) =0.79 vs. eta(F,surf) =0.74, p<.01). This decrease could be
      associated with an increase in swimming frequency for surface swimming (f
      (surf)=2.15Hz vs. f (under)=2.08Hz, p<.01). Active drag during surface swimming
      was about 7% higher than for underwater swimming (AD(under) =78.9N vs. AD(surf)
      =84.7N, p<.01). A significantly smaller cross-sectional area for surface swimming
      (S(under) =0.053m(2) vs. S(surf) =0.044m(2), p<.01) and higher drag coefficient
      for surface swimming (C(d,under) =0.47 vs. C(d,surf) =0.69, p<.01) were measured.
      Finally, correlation between cross-sectional area and vertical amplitude of the
      fin was reported for both underwater and surface swimming. These results suggest
      that the performance improvement during underwater swimming is not only linked to
      a wave drag reduction effect but also to a specific swimming technique due to the
      free surface.

PMID- 19395110
TI  - Deletion of angiotensin II type I receptor reduces hepatic steatosis.
AB  - BACKGROUND/AIMS: A distinct subgroup of angiotensin II type 1 receptor (AT1R)
      blockers (ARBs) have been reported to suppress the development of hepatic
      steatosis. These effects were generally explained by selective peroxisome
      proliferator-activated receptor (PPAR) gamma modulating properties of ARBs,
      independent of their AT1R blocking actions. Here, we provide genetic evidence of
      the direct role for AT1R in hepatic steatosis. METHODS: The effect of AT1R
      deletion on steatohepatitis was investigated in AT1a(-/-) mice. Furthermore, the
      influence of AT1R inhibition by telmisartan as well as gene silencing of AT1R by
      siRNA was assessed in an in vitro experiment using HepG2 cells. RESULTS: Compared
      to wild-type (WT), AT1a(-/-) mice fed methionine-choline deficient (MCD) diet
      resulted in negligible lipid accumulation in the liver with marked induction of
      PPARalpha mRNA. In vitro experiments also demonstrated reduced cellular lipid
      accumulation by telmisartan and AT1R knockdown following exposure of long chain
      fatty acids. This is presumably explained by the observation that the expression
      of PPARalpha and its target genes were significantly up-regulated in specific
      siRNA treated HepG2 cells. CONCLUSIONS: Our data indicate, in addition to
      pharmacological effect of ARBs on PPARgamma activation, a key biological role for
      AT1R in the regulation of hepatic lipid metabolism.

PMID- 19395111
TI  - Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma
      development: a meta-analysis.
AB  - BACKGROUND/AIMS: Hepatitis C virus (HCV) is a known risk factor for
      hepatocellular carcinoma (HCC), but whether the risk varies among patients
      infected with different HCV genotypes is still controversial. We performed a meta
      analysis to clarify whether the genotype 1b is associated with a higher risk of
      HCC than other genotypes. METHODS: We identified 57 relevant papers through a
      literature search to December 2007 but, since age could represent a major
      confounder, we focused the meta-analysis on the 21 studies presenting age
      adjusted risk estimates for HCV genotype 1b vs. other genotypes. We used random
      effects models with the DerSimonian-Laird method and assessed heterogeneity
      between studies and publication bias. RESULTS: Patients infected with HCV
      genotype 1b have almost double the risk to develop HCC than those infected with
      other genotypes (Relative Risk (95% Confidence Intervals) = 1.78(1.36-2.32)). The
      pooled risk estimate was somewhat lower when we restricted the analysis to the
      eight studies conducted in patients with liver cirrhosis (1.60;1.07-2.39) or
      considering the 36 studies presenting only crude data (1.63;1.30-2.06). In seven
      studies excluding patients with liver cirrhosis, the RR (95% CI) increased to
      2.46(1.69-3.59). CONCLUSIONS: This meta-analysis suggests that HCV genotype 1b
      plays an important role in HCC development, especially in patients with early
      stage liver disease.

PMID- 19395112
TI  - Genome-wide association studies reach hepatology.

PMID- 19395113
TI  - Autoimmune hepatitis in Italy: the Bologna experience.
AB  - BACKGROUND/AIMS: Autoimmune hepatitis affects mainly women. It is subdivided into
      type 1 and type 2 according to the autoantibody profile and without
      immunosuppression usually evolves to cirrhosis and end-stage liver failure.
      METHODS: We evaluated clinical, biochemical, immunological and genetic features
      and treatment response of 163 consecutive Italian patients with autoimmune
      hepatitis. RESULTS: At diagnosis, type 1 autoimmune hepatitis showed more
      inflamed liver histology and more pronounced cholestasis, whereas type 2 was more
      common in children. Male and female patients shared similar clinical, biochemical
      and immunological features. Of 89 patients with 5-year follow-up or longer, 23
      patients irrespective of presenting clinical, biochemical and immunological
      features achieved complete remission (normal transaminases and gammaglobulin
      levels) which was maintained with minimal steroid dosage; attempt at treatment
      withdrawal led to disease exacerbation. Complete responders had more often HLA
      DRB1*0401 (p = 0.011) and their risk of disease progression was lower (p <
      0.0001). CONCLUSIONS: Type 1 and type 2 autoimmune hepatitis is one and the same
      disease. Autoimmune hepatitis has similar features in male and female patients.
      HLA DRB1*0401 positive patients are more likely to achieve complete remission.
      Continuous low-dose steroids are necessary to maintain remission, significantly
      reducing the risk of disease progression.

PMID- 19395114
TI  - A systems biology perspective on cholangiocellular carcinoma development: focus
      on MAPK-signaling and the extracellular environment.
AB  - BACKGROUND/AIMS: Multiple genes have been implicated in cholangiocellular
      carcinoma (CCC) development. However, the overall neoplastic risk is likely
      associated with a much lower number of critical physiological pathways. METHODS:
      To investigate this hypothesis, we extracted all published genetic associations
      for the development of CCC from PubMed (genetic association studies, but also
      studies associating genes and CCC in general, i.e. functional studies in cell
      lines, genetic studies in humans, knockout mice etc.) and integrated CCC
      microarray data. RESULTS: We demonstrated the MAPK pathway was consistently
      enriched in CCC. Comparing our data to genetic associations in HCC often
      successfully treated by a multityrosine kinase inhibitor, sorafenib, we
      demonstrated a similar overrepresentation of MAPK. In contrast, most cancer
      related genetic studies focusing on genes related to transcription and cell cycle
      control, we consistently found genes coding for products in the extracellular
      environment to be significantly enriched. Thus, CCC must be regarded as
      developing in the context of an altered extracellular environment. CONCLUSIONS:
      Our study suggests the liver microenvironment holds essential functions and
      structures key to CCC progression. Furthermore, we identified the MAPK signaling
      pathway consistently enriched, pointing towards a critical role in CCC
      development. These data may provide a rationale for treatment of CCC with
      sorafenib.

PMID- 19395115
TI  - Pioglitazone as adjuvant therapy in chronic hepatitis C: sequential rather than
      concomitant administration with pegylated interferon and ribavirin?

PMID- 19395116
TI  - Liver fibrosis: screening is not staging.

PMID- 19395117
TI  - Dynamic decrease in PD-1 expression correlates with HBV-specific memory CD8 T
      cell development in acute self-limited hepatitis B patients.
AB  - BACKGROUND/AIMS: Programmed death-1 (PD-1) upregulation can impair virus-specific
      CD8 T-cell responses during chronic viral infection. Whether and how PD-1 affects
      virus-specific memory CD8 T cells in humans with acute viral infection, however,
      remains largely undefined. METHODS: The association between PD-1 expression and
      HBV-specific memory CD8 T-cell responses were longitudinally analyzed in eighteen
      patients with acute hepatitis B virus (HBV) infection, including ten patients
      with human leucocyte antigen (HLA)-A201 and eight with other HLA-A2 subtypes.
      RESULTS: At clinical onset, PD-1 was significantly up-regulated and subsequently
      led to the functional suppression of HBV-specific effector CD8 T cells, as
      blocking PD-1/PD-L1 interactions in vitro enhanced their proliferation and IFN
      gamma production. Following disease resolution, HBV-specific effector CD8 T cells
      developed into memory T cells. During this period, the dynamic PD-1 decrease was
      numerically correlated with the reduction of HBV-specific CD8 T-cell frequency,
      phenotypically with an acquisition of CCR7, CD45RA and CD127 expressions, and
      functionally with the increase in proliferation and IFN-gamma production of the
      memory T cells. CONCLUSIONS: PD-1-mediated inhibitory signaling not only
      attenuates HBV-specific CD8 T-cell effector function during the acute phase of
      infection but also correlates with the development of HBV-specific memory CD8 T
      cells following disease resolution.

PMID- 19395118
TI  - Determining physiological cross-sectional area of extensor carpi radialis longus
      and brevis as a whole and by regions using 3D computer muscle models created from
      digitized fiber bundle data.
AB  - Architectural parameters and physiological cross-sectional area (PCSA) are
      important determinants of muscle function. Extensor carpi radialis longus (ECRL)
      and brevis (ECRB) are used in muscle transfers; however, their regional
      architectural differences have not been investigated. The aim of this study is to
      develop computational algorithms to quantify and compare architectural parameters
      (fiber bundle length, pennation angle, and volume) and PCSA of ECRL and ECRB.
      Fiber bundles distributed throughout the volume of ECRL (75+/-20) and ECRB (110+/
      30) were digitized in eight formalin embalmed cadaveric specimens. The digitized
      data was reconstructed in Autodesk Maya with computational algorithms implemented
      in Python. The mean PCSA and fiber bundle length were significantly different
      between ECRL and ECRB (p < or = 0.05). Superficial ECRL had significantly longer
      fiber bundle length than the deep region, whereas the PCSA of superficial ECRB
      was significantly larger than the deep region. The regional quantification of
      architectural parameters and PCSA provides a framework for the exploration of
      partial tendon transfers of ECRL and ECRB.

PMID- 19395119
TI  - Hypofractionated radical radiotherapy in elderly patients with medically
      inoperable stage I-II non-small-cell lung cancer.
AB  - We described the results of a hypofractionated regimen (HFRT) in a cohort of
      elderly patients (36 subjects) with stage I-II non-small-cell-lung cancer
      (NSCLC), tumor size> or =3 cm and ineligible for surgery. HFRT was delivered in
      20 daily fractions of 3 Gy per fraction with a total dose of 60 Gy. The median
      PTV was 145 cm(3). The primary purpose of study was to estimate the local tumor
      control at 2 years as well as the modifications in the lung function parameters
      at 6 and 12 months. The local tumor control was 63.9% at 2 years. The incidence
      of distant recurrence rate at 2 years was 50%. The overall-survival (OS), the
      cause-specific-survival (CSS) and the disease-free-survival (DSF) at 2 years were
      55.6, 57.1, and 38.9%, respectively. The median OS, CSS, and DFS was 25.4 (CI 95%
      21.7-32.9), 26.7 (CI 95% 22.5-33.5) and 23.4 months (CI 95% 18.6-30.1),
      respectively. The two clinical parameters with a positive influence on OS were a
      KPS> or =90 (HR 1.16; p=0.013) and tumor size< or =4 cm (HR 0.763; p=0.011). No
      grade 3-4 acute toxicity was reported. No significant change in lung function
      parameters was measured at 6 and 12 months. For patients with larger or centrally
      located tumors as well as for subjects with lymph nodes involvement SBRT may be
      of limited valiance. Although the performances of our regimen were lower than the
      ones achieved by SBRT, our therapeutic option may offer a lower incidence of
      complications against a satisfactory local tumor control.

PMID- 19395120
TI  - Characterisation of a DNAPL source zone in a porous aquifer using the
      Partitioning Interwell Tracer Test and an inverse modelling approach.
AB  - In this paper, we discuss the results of a Partitioning Interwell Tracer Test
      (PITT) performed in a large scale experiment with a well-defined TCE spill, and
      present a novel combined analytical-numerical inverse modelling approach using
      measured concentration profiles within a TCE plume to predict the distribution of
      the DNAPL in a virtual vertical plane of the source. The proposed inverse
      modelling approach assumes local thermodynamic equilibrium of the distribution of
      TCE between the NAPL phase and the aqueous phase and no decay or sorption of the
      dissolved TCE concentrations downstream of the spill area. The analytical part of
      the inverse modelling approach contains two steps. As a first step, the location
      of the contaminant in a virtual vertical plane of a porous medium is fixed by
      using measured concentration profiles and considering the dissolution of the
      organic phase under equilibrium conditions. In the second step, the volume of
      contaminant entrapped in the source cells is estimated. A multiphase advective
      dispersive transport model is used in the final step to adjust the volumes
      quantified in the second step. The predictions are highly dependent on the
      quantity and quality of the data in space and time. From the PITT-breakthrough
      curves measured at the pumping well, a mean TCE saturation in the sweep zone of
      0.0004 was derived, which is very low compared to that determined at the local
      scale. In a second analysis, tracer breakthrough curves available at measuring
      points placed closely downstream and upstream of the presumed source zone, were
      used to explain why the globally obtained DNAPL saturation was very low compared
      to the "real", locally evaluated TCE saturations in the source zone. This was
      principally caused by the overall travel time compared to the short travel time
      of the tracers in the source zone. Another reason is that due to bypassing, only
      part of the volume of tracer injected had been in contact and had eventually
      interacted with the DNAPL. Furthermore, the quantified TCE volume was nearly 30%
      higher than the spilled volume; this agrees with the conclusions from other
      studies emphasizing that calculated volumes can overestimate the measured
      volumes, particularly in the case of an inhomogeneous distribution of the DNAPL
      within the soil. A good agreement of the measured and inversed concentration
      profiles was obtained, highlighting that it is possible to determine the length
      averaged distribution of a residual pollution source from dissolved concentration
      profiles measured downstream of the source zone. The numerically obtained non
      uniform distribution of DNAPL entrapped in the vertical plane of the source zone
      was experimentally confirmed by the TCE saturation values derived from PITT
      breakthrough curves at measuring points located 0.75 m downstream of the source
      zone. However, the sensitivity study showed that the inverse modelling approach
      provided a rather non-unique solution. More data available may reduce the number
      of possible representations of the estimated source zone.

PMID- 19395122
TI  - Incidence and anatomic presentation of cutaneous malignant melanoma in central
      Canada during a 50-year period: 1956 to 2005.
AB  - BACKGROUND: Incidence rates of cutaneous malignant melanoma (CMM) have increased
      worldwide. Long-term studies examining rates and anatomic site-specific incidence
      on a population-based level are infrequent. OBJECTIVE: We sought to examine the
      historical changes in the incidence and anatomic site presentation of CMM during
      a 50-year period in Manitoba, Canada. METHODS: Using population-based data, all
      first diagnoses of CMM reported between 1956 and 2005 were identified. Age
      specific rates, age-standardized incidence rates, and anatomic sites were
      recorded. RESULTS: Incidence rates of CMM slowed for each sex beginning in 1981
      for female patients and 1992 for male patients. Annual percent change revealed
      decreasing rates among male patients younger than 40 years (1992-2005: -5.3% [P =
      .03]) and female patients younger than 40 years (1987-2005: -1.8% [P = .15]).
      Similarly, middle-aged individuals (age 40-59 years) also had diminished annual
      percent change (men 1992-2005: 0.6% [P = .65]; women 1983-2005: -0.3% [P = .68]).
      The annual percent change for older men and women (60-79 and > or =80 years)
      continued to increase. Anatomic site-specific analyses revealed that the trunk
      was the most frequent site of CMM for young male patients (<60 years) whereas the
      lower extremities were the most common among young female patients (<60 years).
      Incidence rates for each site, however, are slowing. Among those aged 60 years
      and older, the rates for each anatomic site increased. LIMITATIONS: Determining
      changes in tumor thickness would have been useful in determining whether the
      nature of tumors have changed over time; however, this is not recorded in our
      registry. CONCLUSION: The rates of CMM are slowing; however, this change is
      confined to younger individuals. Anatomic site-specific CMMs are changing; rates
      among older individuals continue to increase for both sexes.

PMID- 19395121
TI  - The germline stem cells of Drosophila melanogaster partition DNA non-randomly.
AB  - The Immortal Strand Hypothesis proposes that asymmetrically dividing stem cells
      cosegregate chromatids to retain ancestral DNA templates. Using both pulse-chase
      and label retention assays, we show that non-random partitioning of DNA occurs in
      germline stem cells (GSCs) in the Drosophila ovary as these divide asymmetrically
      to generate a new GSC and a differentiating cystoblast. This process is disrupted
      when GSCs are forced to differentiate through the overexpression of Bag of
      Marbles, a factor that impels the terminal differentiation of cystoblasts. When
      Decapentaplegic, a ligand which maintains the undifferentiated state of GSCs, is
      expressed ectopically the non-random partitioning of DNA is similarly disrupted.
      Our data suggest asymmetric chromatid segregation is coupled to mechanisms
      specifying cellular differentiation via asymmetric stem cell division.

PMID- 19395123
TI  - Primary hyperhidrosis increases the risk of cutaneous infection: a case-control
      study of 387 patients.
AB  - BACKGROUND: Although primary hyperhidrosis (PHH) has been frequently associated
      with diminished quality of life, the medical consequences of the condition are
      less well studied. OBJECTIVE: The objective was to study the clinical
      presentation of PHH and to determine its relationship to cutaneous infection.
      METHODS: A retrospective case-control study of patients encountered between 1993
      and 2005 with the International Classification of Diseases, Ninth Revision
      diagnosis code for hyperhidrosis (HH) and meeting criteria for PHH was conducted.
      RESULTS: Of 387 patients with PHH included, 59% were female and 41% were male;
      mean age was 27.3 years (range 2-72). Sites of HH included soles (50.1%), palms
      (45.2%), and axillae (43.4%). Distributional patterns of HH were isolated
      axillary (27.6%), palmoplantar (24.3%), isolated plantar (15%),
      axillary/palmoplantar (5.7%), isolated palmar (5.7%), and craniofacial (5.2%).
      Axillary HH was more common in female patients (P = .004). The mean age of onset
      (18.6 +/- 12.3 years) indicated a mean duration of untreated symptoms of 8.9
      years. Age at onset for palmoplantar HH (11.5 +/- 8 years) was significantly
      younger than for axillary HH (20.0 +/- 8.3 years; P < .0001), whereas onset of
      craniofacial HH (25.4 +/- 13.7 years) was older (P < .001). Exacerbating factors
      included stress/emotion/anxiety (56.7%) and heat/humidity (22%). The overall risk
      of any cutaneous infection was significantly (P < .0001) increased in HH compared
      with controls (odds ratio [OR] 3.2; 95% confidence interval [CI] 2.2-4.6). Site
      specific risks of fungal infection (OR 5.0; 95% CI 2.6-9.8; P < .0001), bacterial
      infection (OR 2.6; 95% CI 1.2-5.7; P = .017), and viral infection (OR 1.9; 95% CI
      1.2-3.0; P = .011) were all increased. Risks of pitted keratolysis (OR 15.4; 95%
      CI 2.0-117; P = .0003), dermatophytosis (OR 9.8; 95% CI 3.4-27.8; P < .0001), and
      verruca plantaris/vulgaris (OR 2.1; 95% CI 1.3-3.6; P = .0077) were particularly
      increased. Association with atopic/eczematous dermatitis (OR 2.9; 95% CI 1.5-55;
      P = .019) was observed. LIMITATIONS: Retrospective design and single-institution
      study are limitations. CONCLUSIONS: Patients with HH are at high risk of
      secondary infection. Management of HH may have a secondary benefit of decreasing
      this risk.

PMID- 19395124
TI  - Five out of 16 plasma signaling proteins are enhanced in plasma of patients with
      mild cognitive impairment and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder with
      characteristic neuropathological changes of the brain. Great efforts have been
      undertaken to determine the progression of the disease and to monitor therapeutic
      interventions. Especially, the analysis of blood plasma had yielded incongruent
      results. Recently, Ray et al. (Nat. Med. 13, 2007, 1359f) identified changes of
      18 signaling proteins leading to an accuracy of 90% in the diagnosis of AD. The
      aim of the present study was to examine 16 of these signaling proteins by
      quantitative Searchlight multiplex ELISA in order to determine their sensitivity
      and specificity in our plasma samples from AD, mild cognitive impairment (MCI),
      depression with and without cognitive impairment and healthy subjects.
      Quantitative analysis revealed an increased concentration in Biocoll isolated
      plasma of 5 out of these 16 proteins in MCI and AD patients compared to healthy
      subjects: EGF, GDNF and MIP1delta (in AD), MIP4 (in MCI) and RANTES (in MCI and
      AD). ROC analysis predicted a sensitivity of 65-75% and a specificity of 52-63%
      when comparing healthy controls versus MCI or AD. Depression without any
      significant cognitive deficits did not cause any significant changes. Depressed
      patients with significant cognitive impairment were not different from MCI
      patients. In conclusion, we detected a number of altered proteins that may be
      related to a disease specific pathophysiology. However, the overall expression
      pattern of plasma proteins could not be established as a biomarker to
      differentiate MCI from AD or from depression.

PMID- 19395125
TI  - [In patients with abdominal pain and a history of high alcohol intake, which
      tests allow the presence of chronic pancreatitis to be confirmed or excluded?].

PMID- 19395126
TI  - [Gastric mucosa as a target of persistent proinflammatory aggression: pathogenic
      models of chronic gastritis].
AB  - There are several causes of damage and regeneration of the gastric epithelium
      (erosive gastropathy) and/or histological inflammation of the gastric mucosa
      (acute or chronic gastritis). After outlining the usual morphology of chronic
      gastritis, the authors attempt to identify the biological profile of the main
      pathogenic models. The first, and by far the most frequent, is the model
      associated with Helicobacter pylori, which, without crossing the mucosal
      epithelium, provokes an immune reaction. Although incapable of eradicating this
      bacterium, this immune reaction contributes to the inflammatory lesion provoked
      by H. pylori in the mucosa. The second -and much less frequent- model is that
      causing progressive atrophic gastritis through a humoral and cellular autoimmune
      mechanism. In third place are a group of models defined by a peculiar
      cytohistologic pattern of inflammation (granulomatous, lymphocytic or
      eosinophilic gastritis), suggesting similar pathogenic mechanisms for each of
      these rare morphological forms of gastritis. Lastly, there is a model barely
      fitting within the scope of this review, which is that provoking chemical
      gastropathies (bile reflux, NSAIDs, etc.) with minimal cellular inflammation,
      i.e., minimal gastritis. To aid understanding of the article, the authors provide
      a brief outline of the functional histology of the gastric wall and the
      mechanisms defending its integrity in physiological conditions.

PMID- 19395127
TI  - [Virus with a denomination of origin: West Nile virus].

PMID- 19395128
TI  - [How to name in Spanish those viruses with a designation of its origin: Sin
      Nombre, Napoles, West Nile].

PMID- 19395129
TI  - Synthesis and in vivo antidiabetic activity of novel dispiropyrrolidines through
      [3+2] cycloaddition reactions with thiazolidinedione and rhodanine derivatives.
AB  - The synthesis of a series of novel dispiropyrrolidines has been accomplished by
      1,3-dipolar cycloaddition reaction with 5-arylidene-1,3-thiazolidine-2,4-dione
      and 5-arylidene-4-thioxo-1,3-thiazolidine-2-one derivatives as dipolarophiles.
      The structure and stereochemistry of the cycloadduct have been established by
      single crystal X-ray structure and spectroscopic techniques. Molecular docking
      studies were performed on 1FM9 protein. The synthesized compounds were screened
      for their antidiabetic activity on male Wistar rats.

PMID- 19395130
TI  - T-cell response to different cultivars of farro wheat, Triticum turgidum ssp.
      dicoccum, in celiac disease patients.
AB  - BACKGROUND & AIMS: Celiac disease is a gluten sensitive disorder that occurs in
      genetically susceptible individuals. The present study deals with variation in
      the immune response of mucosal T-cells from celiac children to prolamins
      extracted from nine landraces of farro wheat (Triticum turgidum ssp. dicoccum)
      with contrasting storage protein compositions. METHODS: The prolamin fraction
      from nine 'dicoccum' wheat landraces was subjected to peptic-tryptic digestion
      and supplied to T-cells from mucosal explants of four celiac patients. Immune
      reactions in terms of cell proliferation and INF-gamma secretion by intestinal T
      lymphocytes were then determined. RESULTS: T-cell lines exposed to digested
      prolamins from landraces L5563, L5558 and L5540 showed negligible proliferative
      responses and released INF-gamma amounts similar to that of untreated control
      cells. By contrast, landraces Ersa 6, Ersa 8, Leonessa 4 and Leonessa 5 proved to
      be very active in triggering the immune responses, whereas landraces Filosini and
      Prometeo exhibited an intermediate behavior. One-dimensional fractionations by A
      PAGE or SDS-PAGE revealed distinctive prolamin patterns amongst the landraces
      analysed. CONCLUSIONS: 'Dicoccum' wheat represents a heterogeneous species
      showing a wide variation in both prolamin composition and T-cell immunological
      activation, some 'dicoccum' landraces being poor in or devoid of noxious gluten
      proteins.

PMID- 19395131
TI  - Isohumulones, the bitter component of beer, improve hyperglycemia and decrease
      body fat in Japanese subjects with prediabetes.
AB  - BACKGROUND & AIMS: A recent study reported that isohumulones, the bitter
      component of beer, activate peroxisome proliferator-activated receptor alpha
      (PPARalpha) and PPARgamma in vitro and decrease plasma glucose and lipid levels
      in diabetic mice. This study was to investigate the efficacy and safety of
      isohumulones for subjects with prediabetes. METHODS: Ninety-four subjects with
      prediabetes were randomly divided into four groups. A 12-week double-blind dose
      finding study was performed in which subjects ingested placebo capsules or test
      capsules containing 16 mg, 32 mg or 48 mg of isohumulones per day. RESULT: After
      treatment, fasting blood glucose was decreased in the 32 mg and 48 mg groups
      after 4 weeks, but did not change in the placebo group. HbA1c was also
      significantly decreased after 4 weeks in the 16 mg group and after 8 weeks in the
      32 mg and 48 mg groups. Body mass index (BMI) was significantly decreased in the
      48 mg group as compared with the placebo group at 12 weeks. The decrease in total
      fat area was also significantly greater in the 48 mg group than in the placebo
      group at 12 weeks. CONCLUSION: The present study suggests that ingestion of
      isohumulones has beneficial effects in diabetes and obesity.

PMID- 19395132
TI  - Malnutrition and epilepsy: a two-way relationship.
AB  - BACKGROUND & AIMS: A link between malnutrition and epilepsy has been suspected
      for many years. METHODS: Different aspects of the question were studied with a
      review of previous published data. RESULTS: Several studies performed on animal
      models or humans highlight the possible adverse effects of malnutrition in the
      onset of seizures. Protein-energy, electrolyte, vitamin or trace element
      deficiencies may be involved. Conversely, several determinants of epilepsy could
      lead to malnutrition: food taboos and social exclusion in developing countries as
      well as some adverse effects of antiepileptic treatments. CONCLUSIONS: Two
      different hypotheses exist as a vicious circle: malnutrition predisposing to
      epilepsy or epilepsy predisposing to malnutrition. A better understanding of
      these interactions is necessary. In the mean time, malnutrition has to be
      prevented and treated.

PMID- 19395133
TI  - Analysis of calvarial bone defects in rats using microcomputed tomography:
      potential for a novel composite material and a new quantitative measurement.
AB  - Reconstruction of craniomaxillofacial defects is a challenge for surgeons and has
      psychological and functional burdens for patients. Undoubtedly, there is a need
      for improved biomaterials and techniques for craniomaxillofacial reconstruction.
      We assessed the potential regeneration of bone using three modifications of a
      novel composite and explored the validity of a new measurement using
      microcomputed tomography (micro-CT). We placed three different composite samples
      in calvarial defects in rats and analysed healing with micro-CT. The results
      showed that polycaprolactone (PCL) with phosphate glass fibre is promising for
      non-load bearing applications in the craniomaxillofacial region. Also, the new
      micro-CT measurement of the temporal characterisation of the mineralisation of
      bone (TCBM) has the potential to evolve into a reliable predictor of bony healing
      and its quality.

PMID- 19395134
TI  - Sublethal effects of herbicides on the biomass and seed production of terrestrial
      non-crop plant species, influenced by environment, development stage and
      assessment date.
AB  - Guidelines provided by the OECD and EPPO allow the use of single-species tests
      performed in greenhouses to assess the risk of herbicides to non-target
      terrestrial plant communities in the field. The present study was undertaken to
      investigate the use of greenhouse data to determine effects of herbicides with a
      different mode of action on the biomass, seed production and emergence of field
      grown plants. In addition, a single species approach was compared with a mixed
      species approach. Effects on the biomass of greenhouse and field-grown plants
      were found to be related at different effect levels, indicating that it might be
      possible to translate results from greenhouse studies to field situations.
      However, the use of single-species tests may not be valid. The response of a
      single plant species to sublethal herbicide dosages differed to the response of
      the same species grown in a mixture with other species.

PMID- 19395135
TI  - Colloid-facilitated transport of lead in natural discrete fractures.
AB  - Colloid-facilitated transport of lead (Pb) was explored in a natural chalk
      fracture with an average equivalent hydraulic aperture of 139 microm. Tracer
      solution was prepared by adding montmorillonite (100 mg L(-1)) and/or humic acid
      (HA) (10 mg L(-1)) to modified artificial rainwater containing dissolved Pb (21.4
      mg Pb L(-1)), naturally precipitated PbCO(3) particles (16.4 mg Pb L(-1)) and
      LiBr (39.0 mg L(-1)). We found that Pb is only mobile when associated with
      colloids. PbCO(3) particles were not mobile in the fracture. The addition of HA
      to the montmorillonite suspension increased the suspension's mobility and
      therefore promoted the colloid-facilitated transport of Pb. The increases in pH
      and sodium absorption ratio induced by the chalk-tracer solution interactions
      appeared to increase the dispersion and mobilization of colloids entering the
      fracture. The dominant colloid-facilitated transport of Pb reported in this study
      has significant implications for risk assessment of Pb mobility in fractured
      rocks.

PMID- 19395137
TI  - Determinants, correlates and mediators of psychological distress: a longitudinal
      study.
AB  - This study examined determinants and correlates of psychological distress
      focusing on the roles of psychosocial resources, such as sense of mastery and
      social support in mediating and/or moderating the effects of life stressors, such
      as unfavourable socioeconomic conditions (SES), poor physical health and chronic
      daily stress on individuals' level of distress. Additionally, the above
      examination was conducted for men and women separately and the results were
      compared. The study was based on secondary analyses of data collected by
      Statistics Canada in two cycles of the National Population Health Survey:
      2002/2003 and 2004/2005. The sample used included 2535 men and 3200 women between
      the ages of 25 and 64 years. Further, this research used structural equation
      techniques to examine pathways among life stressors, psychosocial resources and
      distress and block regression analysis to examine the moderating roles of mastery
      and social support. Chronic daily stress was measured in 2004/2005 and two years
      earlier, in 2002/2003. Main findings included: (1) higher levels of mastery and
      social support were found to be associated with less depressive symptoms for both
      men and women, (2) in addition to its significant main effect on distress,
      mastery moderated the detrimental effects of poor physical health and chronic
      daily stress on depressive symptoms for both genders, (3) the effects of daily
      stress, poor physical health and unfavourable SES on level of distress were
      partially mediated through mastery, (4) next to daily stress, poor physical
      health had the most impact on level of distress for both genders, albeit a
      stronger impact for women, (5) mastery played a more important role in the
      distress process of women compared with men, and (6) while perceived social
      support decreased the likelihood of distress for men directly, it decreased
      women's likelihood of distress by increasing their mastery. Symptoms of distress
      indicate present and/or future need for health care services. Thus, prevention of
      distress may lead to a reduction in health care costs in addition to the
      reduction of subjective suffering. Findings emphasize the importance of
      allocating resources to groups at high risk of developing distress, such as the
      poor and the physically unhealthy.

PMID- 19395136
TI  - Successful pregnancy and delivery of a healthy newborn despite transplacental
      transfer of antimyeloperoxidase antibodies from a mother with microscopic
      polyangiitis.
AB  - Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibodies have been
      proposed as pathogenic for microscopic polyangiitis. Supporting this hypothesis,
      a case report of transplacental anti-MPO antibody transfer presumably causing a
      vasculitis-like syndrome in the newborn is cited frequently. Here, we report a
      case of transplacental transfer of high levels of anti-MPO antibodies not
      resulting in clinical compromise in the newborn. The mother developed microscopic
      polyangiitis 5 years before the pregnancy. After induction therapy, remission was
      maintained with low-dose prednisone and azathioprine for 4.5 years despite high
      levels of anti-MPO antibodies (>100 U/mL). The patient elected to become
      pregnant, immunosuppression was maintained during pregnancy, and a normal-term
      neonate was delivered. The newborn's venous blood anti-MPO antibody levels
      decreased gradually from greater than 100 U/mL at birth to undetectable by day
      120. No clinical manifestation of vasculitis developed in the newborn. This case
      supports that anti-MPO antibodies alone are not pathogenic without additional
      cofactors.

PMID- 19395138
TI  - [Sleep apnea-hypopnea syndrome without excessive daytime sleepiness].
AB  - Nowadays, sleepiness in patients with sleep apnea-hypopnea syndrome (SAHS) is
      understandable. It is somewhat more difficult to explain why most patients with
      SAHS enrolled in epidemiologic studies, even those with a high apnea-hypopnea
      index, do not experience excessive daytime sleepiness. The reasons for this
      discrepancy lie beyond mere polysomnographic events. This review examines data
      from the literature that may help us understand why these patients do not
      experience daytime sleepiness. It also analyzes studies that support and refute
      sleepiness as a marker of cardiovascular risk in patients with SAHS, and
      discusses the mechanisms that might increase this risk.

PMID- 19395139
TI  - [The Archivos Archive, 2008: an overview of research published in Archivos de
      Bronconeumologia].

PMID- 19395140
TI  - [Economic evaluation of smoking cessation interventions: have we overlooked
      something].

PMID- 19395141
TI  - [Survival analysis of resection of lung metastases from colorectal cancer].
AB  - INTRODUCTION: The publication of the International Registry of Lung Metastases
      (IRLM) in 1997 was a turning point in favor of surgical resection of lung
      metastases. Prognostic groups were defined according to resectability, number of
      metastases, and disease-free interval. The objective of this study was to
      determine survival in patients who underwent resection of lung metastases from
      colorectal carcinoma and to evaluate how applicable the prognostic factors
      established by the IRLM are in this specific patient group. PATIENTS AND METHODS:
      Patients with lung metastases from colorectal carcinoma who underwent resection
      between January 1, 2000, and November 30, 2006, were retrospectively analyzed.
      Survival was calculated using the Kaplan-Meier method, with log-rank comparisons
      between groups. RESULTS: Survivals at 1, 3, 5, and 6 years was 92%, 75%, 54%, and
      43%, respectively. The main finding was that 3-year survival was better in
      patients who underwent atypical resection of the metastasis (75%) than those who
      required lobectomy (55%). There were no significant differences in survival in
      terms of number of lung metastases resected or disease-free interval.
      CONCLUSIONS: Survival in patients requiring lobectomy for resection of lung
      metastases from colorectal carcinoma was worse than in those who underwent
      atypical resection. The number of metastases and disease-free interval may be
      questionable prognostic factors in the case of lung metastases from colorectal
      carcinoma.

PMID- 19395142
TI  - Feasibility of point-of-care colour Doppler ultrasound confirmation of
      intraosseous needle placement during resuscitation.
AB  - INTRODUCTION: Intraosseous needle insertion for vascular access is a standard
      procedure used in paediatric resuscitation. The introduction of newer automated
      intraosseous devices has recently expanded its role to include resuscitation in
      patients of all ages. Managing resuscitation can be challenging and a misplaced
      intraosseous needle may confound effective resuscitation. Colour Doppler
      ultrasound has been recently proposed as a method to confirm intraosseous needle
      placement. The ability to rapidly determine the correct position of an
      intraosseous needle during resuscitation would allow the delivery of medication
      or fluid infusion into the vascular space to be verified, thus optimizing
      resuscitation. Furthermore, complications from intraosseous infusion
      extravasating into soft tissues, such as compartment syndrome, or tissue necrosis
      can be avoided. METHODS: We describe the point-of-care sonographic technique and
      colour Doppler ultrasound findings of intraosseous needle confirmation in a case
      series of critically ill patients requiring resuscitation, highlighting the
      utility of this sonographic application. RESULTS: Colour Doppler ultrasound
      detected extraosseous flow in incorrectly positioned intraosseous needles, and
      intraosseous flow in correctly positioned intraosseous needles in six critically
      ill patients requiring resuscitation. CONCLUSIONS: The use of point-of-care
      colour Doppler ultrasound to determine the location of both manually inserted or
      automated placement of intraosseous access during resuscitation is feasible, can
      be rapidly performed, may verify delivery of resuscitative medications or
      infusions, and avoid complications from extravasation.

PMID- 19395143
TI  - An educational course including medical simulation for early goal-directed
      therapy and the severe sepsis resuscitation bundle: an evaluation for medical
      student training.
AB  - OBJECTIVE: Widespread application of early goal-directed therapy (EGDT) and the
      severe sepsis resuscitation bundle is limited by clinician knowledge, skills and
      experience. This study evaluated use of simulation-based teaching during medical
      training to increase future clinician knowledge in the above therapies for severe
      sepsis and septic shock. METHODS: A prospective cohort study was performed with
      medical students at all levels of training. A 5-h course including didactic
      lectures, skill workshops, and a simulated case scenario of septic shock were
      administered to the participants. A checklist including 21 tasks was completed
      during the patient simulation. An 18-question pre-test, post-test and 2-week post
      test were given. The participants completed a survey at the end of the course.
      RESULTS: Sixty-three students were enrolled. There was statistical difference
      between the pre-test and each of the post-test scores: 57.5+/-13.0, 85.6+/-8.8,
      and 80.9+/-10.9%, respectively. 20.6% of participants thought the pre-test was
      too difficult, whereas all participants thought the post-test was either
      appropriate or too easy. The task performance during the simulated septic shock
      patient was 94.1+/-6.0%. The participants noted improvements in their confidence
      levels at managing severe sepsis and septic shock, and agreed that the course
      should be a requirement during medical school training. CONCLUSIONS: Medical
      simulation is an effective method of educating EGDT and the severe sepsis
      resuscitation bundle to medical students with limited experience in patient care.
      The results suggest that our course may be of further benefit at increasing
      clinical experience with this intensive protocol for the management of severe
      sepsis and septic shock.

PMID- 19395145
TI  - Cerebral metabolic rate of oxygen (CMRO2) in pig brain determined by PET after
      resuscitation from cardiac arrest.
AB  - AIM: To assess the regional vulnerability to ischemic damage and
      perfusion/metabolism mismatch of reperfused brain following restoration of
      spontaneous circulation (ROSC) after cardiac arrest. METHOD: We used positron
      emission tomography (PET) to map cerebral metabolic rate of oxygen (CMRO(2)),
      cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in brain of young
      pigs at intervals after resuscitation from cardiac arrest. After obtaining
      baseline PET recordings, ventricular fibrillation of 10 min duration was induced,
      followed by mechanical closed-chest cardiopulmonary resuscitation (CPR) in
      conjunction with i.v. administration of 0.4 U/kg of vasopressin. After CPR,
      external defibrillatory shocks were applied to achieve restoration of spontaneous
      circulation (ROSC). CBF and CMRO(2) were mapped and voxelwise maps of OEF were
      calculated at times of 60, 180, and 300 min after ROSC. RESULTS: There was
      hypoperfusion throughout the telencephalon at 60 min, with a return towards
      baseline values at 300 min. In contrast, there was progressively increasing CBF
      in cerebellum throughout the observation period. The magnitude of CMRO(2)
      decreased globally after ROSC, especially in cerebral cortex. The magnitude of
      OEF in cerebral cortex was 60% at baseline, tended to increase at 60 min after
      ROSC, and declined to 50% thereafter, thus suggesting transition to an ischemic
      state. CONCLUSION: The cortical regions tended most vulnerable to the ischemic
      insult with an oligaemic pattern and a low CMRO(2) whereas the cerebellum instead
      showed a pattern of luxury perfusion.

PMID- 19395147
TI  - Mathematical model of a network of interaction between p53 and Bcl-2 during
      genotoxic-induced apoptosis.
AB  - Ionizing radiation like UV light, gamma and X rays, can produce genotoxic damage
      in fibroblast cells. This injury can be reverted by activation of specific
      nuclear molecules. However, intense genotoxic damage induces the activation of
      the p53 dependent apoptotic pathway. Activated nuclear p53 has the role of a
      transcription factor that switches on the transcription of the Puma protein,
      which once released into the cytoplasm leads to the activation of a network of
      chemical processes that produces cell death. This network is built up with the
      chemical interaction between pro-apoptotic p53, Puma and Bax proteins and the
      anti-apoptotic Bcl2 and Bcl-x(L) proteins. In this work we present a mathematical
      model of this modular network under different regimes of Puma release into the
      cytoplasm. In this model we use a set of coupled nonlinear differential
      equations, which is solved by numerical methods, to determine the nature of the
      equilibrium points of the dynamical system. With this information we construct
      the phase portrait associated with Puma induced apoptosis and we found that once
      the genotoxic injury is produced, Bax levels continuously increase. In this work
      we propose that a possible mechanism for the control of apoptosis is the Bax
      level in the cytoplasm, i.e., Bax is continuously released into the cytoplasm,
      even in absence of Puma, according to the kinetic properties of the set of
      chemical interactions in which the Bcl2/Bax complex takes part. If the damage is
      reverted before the Bax level reaches a threshold value the apoptotic process is
      stopped, otherwise the process goes on until cell death.

PMID- 19395144
TI  - Is the enrollment of racial and ethnic minorities in research in the emergency
      setting equitable?
AB  - BACKGROUND: Concerns have been raised about the enrollment of racial and ethnic
      minorities in research in the emergency setting when it is not possible to obtain
      informed consent. However, there is a paucity of data related to the validity of
      such claims. METHODS: Retrospective comparison of registry enrollment (4/1/2006
      3/31/2007) and trial enrollment (4/1/2007-3/31/2008) from three sites in the
      Resuscitation Outcomes Consortium. Subjects compared met the following criteria:
      (1) shock, defined by blunt or penetrating force to the body with either systolic
      blood pressure (SBP) < or =70 mmHg or SBP 71-90 mmHg and heart rate > or =108
      beats/min and/or (2) traumatic brain injury (TBI), defined by blunt force to the
      head with out-of-hospital Glasgow Coma Score < or =8. RESULTS: Overall, compared
      to a registry there were no differences in the percent of racial or ethnic groups
      enrolled in the clinical trial [odds ratio (OR) for Blacks versus Whites: 0.87,
      95% confidence interval (CI) 0.65-1.16, p=.34; OR for Hispanics versus Whites
      1.04; 95% CI 0.72-1.49, p=.85]. However, Blacks were less likely than Whites to
      be enrolled in the TBI cohort [OR 0.58 (0.34-0.97), p=.04]. CONCLUSIONS: Despite
      some discordance in subgroups, there was no overall difference in the racial and
      ethnic distribution of subjects enrolled in a multi-center clinical trial of
      severe trauma compared to a registry accounting for study entry criteria. These
      findings help address justice concerns about enrollment of racial and ethnic
      minorities in trauma research performed using an exception from informed consent
      under emergency circumstances.

PMID- 19395148
TI  - Robust and ubiquitous GFP expression in a single generation of chicken embryos
      using the avian retroviral vector, RCASBP.
AB  - Functional genomics in avian models has lagged behind that of mammals, and the
      production of transgenic birds has proven to be challenging and time-consuming.
      All current methods rely upon breeding chimeric birds through at least one
      generation. Here, we report a rapid method for the ubiquitous expression of GFP
      in chicken embryos in a single generation (G-0), using the avian retroviral
      vector, Replication-Competent Avian sarcoma-leukosis virus, with a Splice
      acceptor, Bryan RSV Pol (RCASBP). High-titre RCASBP retrovirus carrying eGFP was
      injected into unincubated (stage X) blastoderms in ovo. This resulted in stable
      and widespread expression of eGFP throughout development in a very high
      proportion of embryos. Transgenic tissues were identified by fluorescence and
      immunohistochemistry. These results indicate that chicken blastodermal cells are
      permissive for infection by the RCASBP virus. This system represents a rapid and
      efficient method of producing global gene expression in the chicken embryo. The
      method can be used to generate avian cells with a stable genetic marker, or to
      induce global expression of a gene of choice. Interestingly, in day 8.5 embryos,
      somatic cells the embryonic gonads were predominantly GFP positive but primordial
      germ cells were GFP negative, indicating viral silencing in the embryonic
      germline. This dichotomy in the gonads allows the isolation or enrichment of the
      germ cells through negative selection during embryonic stages. This transgenic
      chicken model is of value in developmental studies, and for the isolation and
      study of avian primordial germ cells.

PMID- 19395149
TI  - Flocculant in wastewater affects dynamics of inorganic N and accelerates removal
      of phenanthrene and anthracene in soil.
AB  - Recycling of municipal wastewater requires treatment with flocculants, such as
      polyacrylamide. It is unknown how polyacrylamide in sludge affects removal of
      polycyclic aromatic hydrocarbons (PAH) from soil. An alkaline-saline soil and an
      agricultural soil were contaminated with phenanthrene and anthracene. Sludge with
      or without polyacrylamide was added while emission of CO(2) and concentrations of
      NH(4)(+), NO(3)(-), NO(2)(-), phenanthrene and anthracene were monitored in an
      aerobic incubation experiment. Polyacrylamide in the sludge had no effect on the
      production of CO(2), but it reduced the concentration of NH(4)(+), increased the
      concentration of NO(3)(-) in the Acolman soil and NO(2)(-) in the Texcoco soil,
      and increased N mineralization compared to the soil amended with sludge without
      polyacrylamide. After 112d, polyacrylamide accelerated the removal of anthracene
      from both soils and that of phenanthrene in the Acolman soil. It was found that
      polyacrylamide accelerated removal of phenanthrene and anthracene from soil.

PMID- 19395150
TI  - Environmental history: a piece in the puzzle for establishing plans for
      environmental management.
AB  - Establishment of plans for environmental planning and management requires that a
      number of natural and societal factors must be taken into consideration. Insights
      into the inherent dynamics of nature as well as the role that past human
      activities have played for establishing the current condition of the landscape
      and the natural environment in general are essential. Many natural and man-made
      changes occur over time scales of decades or centuries, and these are difficult
      to comprehend without a historical perspective. Such a perspective can be
      obtained using palaeoecological studies, i.e. by geochemical and biological
      analyses of lake sediment and peat deposits. To illustrate the long-term dynamics
      of nature and particularly the role of man, we present here five case studies
      from Sweden concerning pollution, lake acidification, lake eutrophication,
      biodiversity, and landscape dynamics and conservation--topics of broad interests-
      and discuss benefits of including a longer time perspective in environmental
      management.

PMID- 19395151
TI  - Compensating aboriginal cultural losses: an alternative approach to assessing
      environmental damages.
AB  - We first identify six primary problems with conventional practice: lack of
      context, inadequate participation from aboriginal communities, exclusion of
      important losses, reliance on market-based measures, neglect of uncertainty, and
      inadequate treatment of time. We then propose a different approach to
      compensation, based on insights from the decision sciences and structured
      decision making. Using case-study examples, we discuss how the proposed approach
      might address common sources of cultural loss and, in a concluding section,
      summarize some of the implications for compensation agreements and for
      environmental management practices.

PMID- 19395152
TI  - Open to debate. The motion: Radiotherapy for prostate cancer preserves sexual
      function to a greater extent than nerve sparing radical prostatectomy.

PMID- 19395153
TI  - Laparoscopic or open nephroureterectomy: which is the more efficient way to go?

PMID- 19395154
TI  - Long-term efficacy of maintenance bacillus Calmette-Guerin versus maintenance
      mitomycin C instillation therapy in frequently recurrent TaT1 tumours without
      carcinoma in situ: a subgroup analysis of the prospective, randomised FinnBladder
      I study with a 20-year follow-up.
AB  - BACKGROUND: The long-term prospective data on bacillus Calmette-Guerin (BCG) and
      mitomycin C (MMC) instillation therapy are limited. OBJECTIVE: To compare the
      long-term benefit of BCG and MMC maintenance therapy in patients with recurrent
      bladder carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Eighty-nine patients with
      frequently recurrent TaT1 disease without carcinoma in situ (CIS) were eligible.
      Originally, the patients were enrolled in the prospective FinnBladder I study
      between 1984 and 1987 and randomised to receive BCG or MMC. Both regimens
      involved five weekly instillations, followed by monthly instillations for 2 yr.
      Because of alkalinising the urine and adjusting the dose to bladder capacity, the
      average concentration of MMC was low: 30-40 mg in 150-200 ml of phosphate buffer.
      Overall median follow-up time was 8.5 yr, whereas the median follow-up time of
      the patients who were still alive was 19.4 yr. MEASUREMENTS: Primary end points
      were time to first recurrence and overall mortality. Secondary end points were
      progression and disease-specific mortality. RESULTS AND LIMITATIONS: Thirty-six
      of 45 patients (80.0%) in the MMC group experienced recurrence in contrast to 26
      of 44 patients (59.1%) in the BCG group. This finding was reflected in
      significantly lower cumulative incidence estimates in the BCG group (p=0.005).
      There was a weak trend for fewer progressions (p=0.1) and cancer-specific deaths
      (p=0.2) in the cumulative incidence analysis, as 4 patients versus 10 patients
      progressed and 4 patients versus 9 patients died from the disease in the BCG
      group versus the MMC group, respectively. No difference existed in the overall
      mortality. The study population, however, was too small for conclusive evidence
      about progression or survival. CONCLUSIONS: An intensive intravesical BCG
      immunotherapy results in a sustained and significant long-term reduction in
      recurrence in frequently recurrent bladder carcinoma. The relatively low
      progression rate during the long follow-up suggests that it may be difficult to
      show significant differences in overall mortality with a substantially larger but
      otherwise similar study population. TRIAL REGISTRATION: Registration was not
      considered to be necessary at this stage of the follow-up because the study was
      initiated as early as 1984 and the last randomisation took place in July 1987,
      that is, long before the current requirements concerning study registrations were
      implemented.

PMID- 19395155
TI  - Isolated fatty liver from prolonged propofol use in a pediatric patient with
      refractory status epilepticus.
AB  - Propofol is a widely used rapidly acting sedating or hypnotic agent in the
      intensive care setting. It is generally considered safe in both pediatric and
      adult patients and has been used frequently in cases of refractory status
      epilepticus. The formulation of propofol is highly lipophilic to facilitate
      central nervous system penetration and has a high fat content, and prolonged
      infusions have been known to cause both extrahepatic complications and
      hepatomegaly secondary to fatty liver. Whereas extrahepatic manifestations of
      prolonged propofol infusions have been well reported in non-neurologic intensive
      care patients, cases of pathologically confirmed fatty liver in patients with
      status epilepticus are relatively few. Furthermore, these cases of hepatomegaly
      and fatty liver have been also in the context of concomitant extrahepatic side
      effects. We report on a pediatric patient with refractory status epilepticus
      treated with a prolonged propofol infusion who developed isolated pathologically
      confirmed fatty liver without the usually reported extrahepatic manifestations.

PMID- 19395156
TI  - Kinetics of adsorption of 2-chloroethylethylsulphide on Al2O3 nanoparticles with
      and without impregnants.
AB  - Alumina nanoparticles in the size range of 2-30 nm and surface area 375 m(2)/g
      were synthesized using aerogel route and then characterized using N(2)-BET, SEM,
      TEM, XRD, FTIR and TGA techniques. Thereafter, these were impregnated with
      reactive chemicals and tested for their potential by conducting studies on
      kinetics of adsorption of 2-chloroethylethylsulphide (2-CEES) under static
      conditions. Kinetics was studied using linear driving force and Fickian diffusion
      model. The kinetics parameters such as equilibration constant, equilibration
      capacity, diffusional exponent and adsorbate-adsorbent interaction constant were
      also determined. AP-Al(2)O(3) with 10% impregnation of MoVPA (V(3)) and NaOH
      showed the maximum (574 mg/g) and minimum (88 mg/g) uptake of 2-CEES among
      impregnated systems respectively. All impregnated systems except NaOH
      impregnation showed the values of diffusional exponent to be <0.5, indicated the
      diffusion mechanism to be Fickian, whereas AP-Al(2)O(3) with and without NaOH
      impregnation showed the diffusional mechanism to be anomalous. Hydrolysis and
      dehydrohalogenation reactions (identified using GC/MS technique) were found to be
      the route of degradation of 2-CEES.

PMID- 19395157
TI  - Pt-catalyzed ozonation of aqueous phenol solution using high-gravity rotating
      packed bed.
AB  - In this study, a high-gravity rotating packed bed (HGRPB or HG) was used as a
      catalytic ozonation (Cat-OZ) reactor to decompose phenol. The operation of HGRPB
      system was carried out in a semi-batch apparatus which combines two major parts,
      namely the rotating packed bed (RPB) and photo-reactor (PR). The high rotating
      speed of RPB can give a high volumetric gas-liquid mass transfer coefficient with
      one or two orders of magnitude higher than those in the conventional packed beds.
      The platinum-containing catalyst (Dash 220N, Pt/gamma-Al(2)O(3)) and activated
      alumina (gamma-Al(2)O(3)) were packed in the RPB respectively to adsorb molecular
      ozone and the target pollutant of phenol on the surface to catalyze the oxidation
      of phenol. An ultra violet (UV) lamp (applicable wavelength lambda=200-280 nm)
      was installed in the PR to enhance the self-decomposition of molecular ozone in
      water to form high reactive radical species. Different combinations of advanced
      oxidation processes (AOPs) with the HGRPB for the degradation of phenol were
      tested. These included high-gravity OZ (HG-OZ), HG catalytic OZ (HG-Cat-OZ), HG
      photolysis OZ (HG-UV-OZ) and HG-Cat-OZ with UV (HG-Cat-UV-OZ). The decomposition
      efficiency of total organic compound (eta(TOC)) of HG-UV-OZ with power of UV
      (P(UV)) of 16W is 54% at applied dosage of ozone per volume sample m(A,in)=1200
      mg L(-1) (reaction time t=20 min), while that of HG-OZ without the UV irradiation
      is 24%. After 80 min oxidation (m(A,in)=4800 mg L(-1)), the eta(TOC) of HG-UV-OZ
      is as high as 94% compared to 82% of HG-OZ process. The values of eta(TOC) for HG
      Cat-OZ process with m(S)=42 g are 56% and 87% at m(A,in)=1200 and 4800 mg L(-1),
      respectively. By increasing the catalyst mass to 77 g, the eta(TOC) for the HG
      Cat-OZ process reaches 71% and 90% at m(A,in)=1200 and 4800 mg L(-1),
      respectively. The introduction of Pt/gamma-Al(2)O(3) as well as UV irradiation in
      the HG-OZ process can enhance the eta(TOC) of phenol significantly, while gamma
      Al(2)O(3) exhibits no significant effect on eta(TOC). For the HG-Cat-UV-OZ
      process with m(S)=42 g, the values of eta(TOC) are 60% and 94% at m(A,in)=1200
      and 4800 mg L(-1), respectively. Note that the decomposition of TOC via HG-UV-OZ
      is already vigorous. Thus, the enhancing effect of catalyst on eta(TOC) is minor.

PMID- 19395158
TI  - Kinetics of methylene blue removal from aqueous solution using gulmohar (Delonix
      regia) plant leaf powder: multivariate regression analysis.
AB  - Effects of process variables namely pH, dye concentration, adsorbent dosage,
      temperature, particle size and agitation speed on kinetics of methylene blue
      adsorption onto gulmohar plant leaf powder were investigated. Quadratic models
      were proposed to predict pseudo second order rate constant and equilibrium uptake
      in terms of the process variables. Model coefficients were determined by multiple
      regression analysis. Statistical tools like Student's t-test, F-test, ANOVA and
      lack-of-fit were used to define the most important process variables. The
      proposed models could predict the rate constant and equilibrium dye uptake with
      high R(2) values (0.94 and 0.947). It was found that rate constant increased with
      decrease in concentration, decrease in particle size, increase in adsorbent
      dosage, increase in agitation speed and increase in temperature. Meanwhile, it
      was found that equilibrium dye uptake increased with increase in concentration
      and decrease in dosage. Apart from these combined effects of the process
      variables were established through multiple regression analysis. Langmuir
      monolayer adsorption capacity of GUL was found to be 186.22 mg/g.

PMID- 19395159
TI  - Ozonation of clofibric acid catalyzed by titanium dioxide.
AB  - The removal of clofibric acid from aqueous solution has been investigated in
      catalytic and non-catalytic semicontinuous ozonation runs. Kinetic data were
      analyzed using second order expressions for the reaction between organics and
      ozone or hydroxyl radicals. Catalytic runs used a commercial titanium dioxide
      catalyst consisting of fumed colloidal particles. The kinetic constant of the non
      catalytic ozonation of clofibric acid at pH 3 was 8.16 x 10(-3)+/-3.4 x 10(-4)L
      mmol(-1)s(-1). The extent of mineralization during non-catalytic runs ranged from
      50% at pH 7 to 20% at pH 3 in a reaction that essentially took place during the
      first 10-20 min. The catalyst increased the total extent of mineralization, its
      effect being more important during the first part of the reaction. The pseudo
      homogeneous catalytic rate constant was 2.17 x 10(-2) L mmol(-1)s(-1) at pH 3 and
      6.80 x 10(-1)L mmol(-1)s(-1) at pH 5, with up to a threefold increase with
      respect to non-catalytic constants using catalyst load of 1g/L. A set of stopped
      flow experiments were designed to elucidate the role of catalyst, whose effect
      was probably due to the adsorption of organics on catalytic sites rather than to
      the promotion of ozone decomposition.

PMID- 19395160
TI  - Equilibrium and kinetics study on the adsorption of perfluorooctanoic acid from
      aqueous solution onto powdered activated carbon.
AB  - Powdered activated carbon (PAC) was applied to remove perfluorooctanoic acid
      (PFOA) from the aqueous PFOA solution in this study. Contact time, adsorbent dose
      and temperature were analyzed as the effect factors in the adsorption reaction.
      The contact time of maximum PFOA uptake was around 1h while the sorption removal
      efficiency increased with the PAC concentrations. And the process of adsorption
      increased from 303 K to 313 K and then decreased from 313 K to 323 K. Among four
      applied models, the experimental isotherm data were discovered to follow Langmuir
      isotherm model more closely. Thermodynamically, adsorption was endothermic
      because enthalpy, entropy and Gibbs constants were 198.5 kJ/mol, 0.709 kJ/mol/K
      and negative, respectively, which also indicated that the adsorption process was
      spontaneous and feasible. From kinetic analysis, the adsorption was suggested to
      be pseudo-second-order model. The adsorption of PFOA on the PAC was mainly
      controlled by particle diffusion.

PMID- 19395161
TI  - Recovery of rare metal compounds from nickel-metal hydride battery waste and
      their application to CH4 dry reforming catalyst.
AB  - The recovery of valuable components such as nickel from nickel-metal hydride (Ni
      MH) battery waste by chemical processes and their applications to CH(4) dry
      reforming catalysts were investigated. Three types of compound, identified by XRD
      analysis as NiO, CeO(2) and LaCoO(3) phases, were successfully separated from the
      waste by a series of chemical processes at room temperature using aqueous
      solutions of HCl, NaOH and NH(3), and Ni component of approximately 70% in Ni-MH
      battery waste was recovered. The separated NiO, CeO(2) and LaCoO(3) showed
      catalytic activities for CH(4) dry reforming. In particular, the separated NiO
      easily reduced to Ni(0) at an initial stage, and exhibited excellent catalytic
      activity in terms of CH(4) conversion and stability. Furthermore, it was found
      that the resulting Ni from separated NiO exhibited an anomalous catalysis from
      the comparison with that from regent NiO.

PMID- 19395162
TI  - Enhancement of phenol degradation using immobilized microorganisms and organic
      modified montmorillonite in a two-phase partitioning bioreactor.
AB  - A study was conducted to determine the potential of a two-phase partitioning
      bioreactor (TPPB) for enhancing the treatment of phenol at high initial
      concentrations. TPPBs are characterized by a cell-containing aqueous phase and an
      immiscible and biocompatible organic phase that partitions toxic substrates to
      the biocatalyst on the basis of their metabolic demand and the thermodynamic
      equilibrium of the system. In the present work, in order to enhance the
      degradation of phenol in TPPB, the polysulfone capsule containing organic
      modified montmorillonite (OMMT-PSF capsule) was used as organic phase, and
      polyurethane foam immobilized microorganism (PUF-immobilized microorganism) was
      used as biocatalyst. Experiments showed that OMMT-PSF capsules offered improved
      sorption capacity (30.2mg phenol/g OMMT-PSF capsules at the fixed initial phenol
      concentration of 2030.2mg/L) and a greater sorption rates (the equilibriums were
      reached at about 6h). The characters of vast sorption capacity and rapid sorption
      rates are in accordance with the desire of delivery agent in TPPB, further
      testing demonstrated that OMMT-PSF capsules using as a reservoir in TPPB played a
      significant role. The phenol biodegradation rates of batch fermentation were
      examined, the maximum volumetric consumption rate of phenol decreased in the
      order: immobilized microorganisms with OMMT-PSF capsules in a TPPB (342.4
      mg/(Lh))>immobilized microorganisms without OMMT-PSF capsules (300 mg/(Lh))>free
      microorganisms with OMMT-PSF capsules in a TPPB (208.4 mg/(Lh))>free
      microorganisms without OMMT-PSF capsules (125.8 mg/(Lh)). This work demonstrates
      that the use of immobilized microorganisms and OMMT-PSF capsules in TPPB offers
      improved degradation of phenol.

PMID- 19395163
TI  - Degradation of dimethyl disulfide using homogeneous Fenton's reaction.
AB  - In this work the degradation of a model odor compound (dimethyl disulfide, DMDS)
      using Fenton's reaction is reported. Dimethyl disulfide is present in wastewaters
      generated during production of poultry feather and viscera meal. Oxidation was
      carried out in batch reactor with temperature control. Experimental design
      technique was used to investigate the influence of concentration of hydrogen
      peroxide and Fe(2+), temperature and pH on degradation of DMDS. Control reactions
      using H(2)O(2) without Fe(2+) were carried out, but DMDS degradation could only
      reach 60% for a 0.025 mg L(-1) DMDS solution, at pH 3, 60 degrees C using 10,000
      mg L(-1) H(2)O(2) in 30 min of reaction. The Fenton's reaction could effectively
      remove DMDS, reaching 95% degradation at pH 3, 60 degrees C, 5 mg L(-1) H(2)O(2)
      and 1 mg L(-1) Fe(2+) after only 10 min of contact. A kinetic study of the
      Fenton's reaction was carried out, varying the concentration of hydrogen
      peroxide, Fe(2+) and temperature.

PMID- 19395164
TI  - Simultaneous determination of pesticides at trace levels in water using
      multiwalled carbon nanotubes as solid-phase extractant and multivariate
      calibration.
AB  - The application of solid-phase extraction with multivariate calibration for
      simultaneous determination of three toxic pesticides in tap and reservoir waters
      was presented. The proposed analytical method was used for the determination of
      atrazine, methidathion, and propoxur in complex water samples without the need
      for chromatographic separation. Among the applied multivariate calibration
      methods, partial least squares (PLS-1) method was found the most effective for
      pesticides quantification. Multiwalled carbon nanotubes (MWCNTs) adsorbent showed
      a perfect extraction/preconcentration of pesticides present at trace levels. The
      experimental factors that affect pesticides extraction by MWCNTs adsorbent such
      as sample volume, eluent volume, solution pH, and extraction flow rate were
      studied and optimized. The figures of merit of the proposed method were: limits
      of detection 3, 2, and 3 microg l(-1) and linear ranges 5-30, 3-60, and 5-40
      microg l(-1) for atrazine, methidathion, and propoxur, respectively. A good
      precision was reported for the method, R.S.D. values were always less than 5.0%.
      Satisfactory results were reported for simultaneous determination of trace levels
      of pesticides in complex matrices. In tap water, the percent recoveries for
      pesticides were extended from 95 to 104% and R.S.D. from 1 to 3%, while lower
      recoveries were observed in reservoir water: 84-93% (R.S.D.: 1-3). Although the
      pesticides can be accurately quantified by SPE and liquid chromatography, SPE-PLS
      1 method was found simpler and operated at lower running costs.

PMID- 19395165
TI  - Modification on natural clinoptilolite zeolite for its NH4+ retention capacity.
AB  - The scope of this study was to modify the natural clinoptilolite zeolite
      available locally (Akita Prefecture, Japan) for its ammonium ions retention
      capacity. The natural clinoptilolite was modified chemically and mechanically
      with changing time duration of sodium hydroxide treatment and ball to powder mass
      ratio in wet ball milling, respectively. The ammonium ions retention capacity of
      thus obtained modified clinoptilolites were found to sharply increase with either
      increasing alkaline metal cations content or increasing specific surface area
      (decreasing particle size) of the clinoptilolite. The main mechanism of ammonium
      ions retention is ion exchange and Na(+) ions were observed to be more easily
      exchanged for ammonium ions. The sorption isotherms were good fit to the Langmuir
      model in the cases of natural and chemically modified clinoptilolites while
      Freundlich model was favorable in the case of mechanically modified
      clinoptilolites. The maximum NH(4)(+) retention capacities of natural
      clinoptilolite (NZeo), clinoptilolite treated with NaOH solution for 72h (Zeo-72)
      and wet-milled clinoptilolite (WM-50) according to Langmuir model were 0.89, 1.15
      and 1.39 mmol/g, respectively. The overall reaction is pseudo-second-order with
      rate constant of 3.6 x 10(-2)dm(3)g/(mmol min). It was possible to enhance the
      NH(4)(+) retention capacity of natural clinoptilolite just by decreasing particle
      size without incorporating any further exchangeable cations within the framework
      of zeolite.

PMID- 19395166
TI  - Wet air co-oxidation of decabromodiphenyl ether (BDE209) and tetrahydrofuran.
AB  - The wet air co-oxidation (WACO) of a major commercial polybrominated diphenyl
      ether flame retardant congener, decabromodiphenyl ether (BDE209), was
      investigated using tetrahydrofuran (THF) as an initiator in a stainless autoclave
      at temperature range of 120-170 degrees C and 0.5MPa oxygen pressure. Compared to
      the single oxidation of BDE209 under the same conditions, the addition of THF in
      the reaction system greatly improved the removal efficiency of BDE209. The effect
      of temperature on the reaction was studied. The removals of BDE209 and Br
      increased with increasing temperature. In addition, the effect of NaNO(2) as the
      catalyst on the WACO was also investigated and the results showed that the
      addition of NaNO(2) could improve the Br removal efficiency.

PMID- 19395167
TI  - Study on the treatment of photovoltaic wastewater using electrocoagulation:
      fluoride removal with aluminium electrodes--characteristics of products.
AB  - In this work, treatment of synthetic fluoride-containing solutions by
      electrocoagulation method using aluminium electrodes has been studied.
      Electrocoagulation was investigated for applied potential (10-30 V), electrolysis
      time and supporting electrolyte (NaCl) concentration (0-100mg/L). The results
      showed that with increasing applied potential and electrolysis time, the Al(3+)
      dosage increases, and thereby favouring the fluoride ions removal. It was also
      observed that defluoridation is dependant on the concentration of supporting
      electrolyte. Finally, X-ray diffraction, scanning electron microscopy, energy
      dispersive spectroscopy of X-rays and Fourier transform infrared spectroscopy
      were used to characterize the solid products formed by aluminium electrodes
      during the EC process.

PMID- 19395168
TI  - Simultaneous photocatalytic oxidation of As(III) and humic acid in aqueous TiO2
      suspensions.
AB  - The simultaneous photocatalytic oxidation of As(III) and humic acid (HA) in
      aqueous Degussa P25 TiO(2) suspensions was investigated. Preliminary
      photocatalytic studies of the binary As(III)/TiO(2) and HA/TiO(2) systems showed
      that As(III) was oxidized more rapidly than HA and the extent of photocatalytic
      oxidation of each individual component (i.e. As(III) or HA) increased with
      decreasing its initial concentration and/or increasing catalyst loading. The
      simultaneous photocatalytic oxidation of As(III) and HA in the ternary
      As(III)/HA/TiO(2) system showed that both As(III) and HA oxidation was reduced in
      the ternary system compared to the corresponding binary systems. The effect of
      operating conditions in the ternary system, such as initial As(III), HA and
      TiO(2) concentrations (in the range 3-20mg/L, 10-100mg/L and 50-250 mg/L
      respectively), initial solution pH (3.6-6.7) and reaction time (10-30 min), on
      photocatalytic As(III) and HA oxidation was assessed implementing a two-level
      factorial experimental design methodology. Seven and ten factors were found
      statistically important in the case of photocatalytic As(III) and HA oxidation
      respectively. Based on these statistically significant factors, a first order
      polynomial model describing As(III) and HA photocatalytic oxidation was
      constructed and a very good agreement was obtained between the experimental
      values and those predicted by the model, while the observed differences may be
      readily explained as random noise.

PMID- 19395169
TI  - Optimization of Brazilian TNT industry wastewater treatment using combined zero
      valent iron and fenton processes.
AB  - This work explores the optimization of combined zero-valent iron and fenton
      processes for the treatment of TNT industry wastewater, a residue with recognized
      polluting potential due to its high concentration of 2,4,6-trinitrotoluene and
      extremely acidic pH due of the nature of the product purification process. The
      results of the optimization study indicate that the most efficient condition for
      reducing the concentration of TNT also generates sufficient amounts of
      iron(II)for the subsequent oxidative treatment through the Fenton reaction. In
      general, it was observed that the treatment was highly efficient in terms of
      meeting the main associated environmental parameters, since it reduced acute
      toxicity, removed 100% of TNT, 100% of the organic nitrogen and 95.4% of the COD.

PMID- 19395170
TI  - Valorisation of wastewater from two-phase olive oil extraction in fired clay
      brick production.
AB  - Wastewater issued from oil-washing stage (OWW) in the two-phase olive oil
      extraction method was used to replace fresh water in clay brick manufacture. The
      extrusion trials were performed with one of the ceramic bodies currently being
      used in a local brick factory for red facing bricks (RB) production. Fresh water
      or OWW was added to a final consistency of 2.4 kg/cm(2), the same value as used
      at industrial scale for this kind of clay mixture. Comparative results of
      technological properties of facing bricks are presented. Results show that the
      products obtained with olive oil wastewater are comparable to traditional ones in
      terms of extrusion performance and technological properties of end products. Even
      dry-bending strength of the body formed by wastewater improves by 33% compared to
      fresh water body. In addition, heating requirements can be reduced in the range
      2.4-7.3% depending on the final product. This application can alleviate
      environmental impacts from the olive oil extraction industry and, at the same
      time, result in economic savings for the brick manufacturing industry.

PMID- 19395171
TI  - Removal of heavy metal ions from municipal solid waste leachate using coal fly
      ash as an adsorbent.
AB  - The purpose of this study was to investigate the possibility of the utilization
      of coal fly ash as a low cost adsorbent material for the adsorption of heavy
      metal ions (Zn, Pb, Cd, Mn and Cu) present in the municipal solid waste leachate.
      Batch experiments were conducted to determine the effect of contact time and fly
      ash dosage on adsorption of heavy metals. Experimental data were evaluated to
      find out kinetic characteristics of the adsorption process. The isothermal data
      could be well described by the Freundlich adsorption model. Kinetic parameters of
      adsorption such as the pseudo first-order constant, pseudo second-order constant
      and the intraparticle diffusion rate constant were determined. The fly ash
      concentration required to achieve maximum heavy metal removal was found to be
      2g/L with the removal efficiencies of 39%, 28%, 74%, 42% and 71% for Cu, Mn, Pb,
      Zn and Cd respectively. The results of the study demonstrated that the fly ash
      could be used as an effective low cost adsorbent for the removal of heavy metal
      ions from municipal solid waste leachate.

PMID- 19395172
TI  - Involvement of ligninolytic enzymes of Phanerochaete chrysosporium in treating
      the textile effluent containing Astrazon Red FBL in a packed-bed bioreactor.
AB  - The effect of Tween80, Mn(II) and veratryl alcohol (VA) on the production of
      ligninolytic enzymes of Phanerochaete chrysosporium in a packed-bed bioreactor
      using small pieces of Kissiris as carrier, was investigated. The results of the
      enzyme activities were noticeable in terms of decolorization and COD removal of
      the textile effluent containing an azo dye (Astrazon Red FBL). No dilution was
      made on the tested textile effluent and it was not sterilized, also. Maximum
      decolorization of the dye (87%) and COD removal (42%), both occurred when only
      Tween80 (0.05%, w/v) was added to the effluent. The maximum activities of lignin
      peroxidase (LiP) and manganese peroxidase (MnP) were (U/l): 17 and 52,
      respectively. The role of MnP was pronounced in the dye decolorization process,
      while the influence of LiP was noticeable on COD removal. The reusability of the
      original biomass was examined by replacing undiluted textile effluent (i.e., five
      times). The cellular performance of the original biomass in repeated-batch
      operations was promising.

PMID- 19395173
TI  - Can extremely low or high morphine formation from codeine be predicted prior to
      therapy initiation?
AB  - Activation of codeine by O-demethylation into morphine is a prerequisite for its
      analgesic effects and severe toxicity. Identifying patients in whom morphine is
      formed either at extremely low or at extremely high amounts may improve efficacy
      and safety of codeine therapy. To assess how well this identification is
      possible, we compared the performance of current CYP2D6 phenotype association
      systems (traditional genotype-based classification, a recently proposed CYP2D6
      activity score, and the plasma dextromethorphan metabolic ratio) in 57 healthy
      Caucasians after oral administration of 30 mg dextromethorphan hydrobromide or 50
      mg codeine. Most subjects (87.5%) at the lower 15% of morphine formation from
      codeine and thus likely to not to respond to codeine therapy were correctly
      identified by CYP2D6 genotype- or phenotype-based systems. In contrast, in
      subjects at the upper 15% of morphine formation being at risk for opioid
      toxicity, CYP2D6 genotyping predicted only the 50% who carried gene duplication,
      whereas dextromethorphan-based phenotyping identified 67.5% of the subjects with
      high morphine formation. However, satisfactory prediction (87.5%) of high
      morphine formation was only achieved when combining genotyping with phenotyping.
      In conclusion, insufficient morphine formation from codeine and thus likely
      failure of analgesia can currently be well predicted. However, to make codeine
      therapy safe, extremely high morphine formation has to be predicted as well,
      which has to be obtained at the effort of combining genotyping with phenotyping.

PMID- 19395174
TI  - Formation of large ordered domains in benzenethiol self-assembled monolayers on
      Au(111) observed by scanning tunneling microscopy.
AB  - Benzenethiol (BT) self-assembled monolayers (SAMs) on Au(111) were prepared as a
      function of solution temperature after immersion in a 1mM ethanol solution for 1
      day. The surface structures of BT SAMs were examined by means of scanning
      tunneling microscopy (STM). Although BT molecules usually form disordered SAMs
      containing the Au adatom islands at room temperature, we found that they formed
      two-dimensional ordered SAMs containing a large size domain at a high solution
      temperature of 50 or 75 degrees C. High-resolution STM imaging revealed that BT
      SAMs on Au(111) formed at 50 degrees C have a (2x3 radical2)R23 degrees packing
      structure. From our STM study, we revealed that two-dimensional ordered BT SAMs
      on Au(111) can be obtained by changing the solution temperature.

PMID- 19395175
TI  - Toxoplasmosis in sheep--the last 20 years.
AB  - Sheep are important to the economy of many countries because they are a source of
      food for humans. Sheep are commonly infected with the protozoan parasite,
      Toxoplasma gondii. Infection with the parasite may cause early embryonic death
      and resorption, fetal death and mummification, abortion, stillbirth, and neonatal
      death. Severity of infection is associated with the stage of pregnancy at which
      the ewe becomes infected, the earlier in gestation, the more severe the
      consequences. Infected sheep meat is a source of T. gondii infection for humans
      and carnivorous animals. Most sheep acquire T. gondii infection after birth, and
      less than 4% of persistently infected sheep transmit the parasite vertically to
      the next generation. Recent studies by a group of researchers in England reported
      that repeat ovine transmission of T. gondii may be more common than previously
      believed but these findings are soley based on PCR data and require additional
      data using other techniques to verify the findings. Following infection with T.
      gondii, sheep develop humoral and cell-mediated immune responses against the
      parasite that provides effective protection against disease in subsequent
      pregnancies. A commercial vaccine is available, comprising a live, incomplete
      strain of T. gondii. The vaccine is administered to sheep prior to mating to
      protect against lamb losses due to toxoplasmosis. In the present paper,
      information on the prevalence, transmission, and control of ovine toxoplasmosis
      in the last 20 years is reviewed.

PMID- 19395176
TI  - Examining the psychometric properties and predictive validity of a youth-specific
      version of the Nicotine Dependence Syndrome Scale (NDSS) among teens with varying
      levels of smoking.

PMID- 19395177
TI  - Factor structure of the SOCRATES questionnaire in hospitalized medical patients.
AB  - The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), a 19
      item instrument developed to assess readiness to change alcohol use among
      individuals presenting for specialized alcohol treatment, has been used in
      various populations and settings. Its factor structure and concurrent validity
      has been described for specialized alcohol treatment settings and primary care.
      The purpose of this study was to determine the factor structure and concurrent
      validity of the SOCRATES among medical inpatients with unhealthy alcohol use not
      seeking help for specialized alcohol treatment. The subjects were 337 medical
      inpatients with unhealthy alcohol use, identified during their hospital stay.
      Most of them had alcohol dependence (76%). We performed an Alpha Factor Analysis
      (AFA) and Principal Component Analysis (PCA) of the 19 SOCRATES items, and forced
      3 factors and 2 components, in order to replicate findings from Miller and
      Tonigan (Miller, W. R., & Tonigan, J. S., (1996). Assessing drinkers' motivations
      for change: The Stages of Change Readiness and Treatment Eagerness Scale
      (SOCRATES). Psychology of Addictive Behavior, 10, 81-89.) and Maisto et al.
      (Maisto, S. A., Conigliaro, J., McNeil, M., Kraemer, K., O'Connor, M., & Kelley,
      M. E., (1999). Factor structure of the SOCRATES in a sample of primary care
      patients. Addictive Behavior, 24(6), 879-892.). Our analysis supported the view
      that the 2 component solution proposed by Maisto et al. (Maisto, S.A.,
      Conigliaro, J., McNeil, M., Kraemer, K., O'Connor, M., & Kelley, M.E., (1999).
      Factor structure of the SOCRATES in a sample of primary care patients. Addictive
      Behavior, 24(6), 879-892.) is more appropriate for our data than the 3 factor
      solution proposed by Miller and Tonigan (Miller, W. R., & Tonigan, J. S., (1996).
      Assessing drinkers' motivations for change: The Stages of Change Readiness and
      Treatment Eagerness Scale (SOCRATES). Psychology of Addictive Behavior, 10, 81
      89.). The first component measured Perception of Problems and was more strongly
      correlated with severity of alcohol-related consequences, presence of alcohol
      dependence, and alcohol consumption levels (average number of drinks per day and
      total number of binge drinking days over the past 30 days) compared to the second
      component measuring Taking Action. Our findings support the view that the
      SOCRATES is comprised of two important readiness constructs in general medical
      patients identified by screening.

PMID- 19395178
TI  - Laboratory-based, cue-elicited craving and cue reactivity as predictors of
      naturally occurring smoking behavior.
AB  - Cigarette craving, one hallmark sign of nicotine dependence, is often measured in
      laboratory settings using cue reactivity methods. How lab measures of cue
      reactivity relate to real world smoking behavior is unclear, particularly among
      non-treatment seeking smokers. Within a larger study of hormonal effects on cue
      reactivity (N=78), we examined the predictive relationship of cue reactivity to
      smoking, each measured in several ways. Results indicated that cue-evoked craving
      in response to stressful imagery, and to a lesser extent, in vivo smoking cues,
      significantly predicted smoking behavior during the week following testing.
      However, this predictive relationship was absent upon controlling for reactivity
      to neutral cues. Nicotine dependence may moderate the relationship between cue
      reactivity and actual smoking, such that this predictive relationship is less
      robust among highly dependent smokers than among smokers low in nicotine
      dependence. The question of whether cue-elicited craving predicts smoking among
      smokers not in treatment is best answered with a qualified yes, depending on how
      craving is manipulated and measured. Our findings highlight important
      methodological and theoretical considerations for cue reactivity research.

PMID- 19395179
TI  - A cognitive behavioral therapy for co-occurring substance use and posttraumatic
      stress disorders.
AB  - Co-occurring posttraumatic stress disorder (PTSD) is prevalent in addiction
      treatment programs and a risk factor for negative outcomes. Although
      interventions have been developed to address substance use and PTSD, treatment
      options are needed that are effective, well tolerated by patients, and
      potentially integrated with existing program services. This paper describes a
      cognitive behavioral therapy (CBT) for PTSD that was adapted from a treatment for
      persons with severe mental illnesses and PTSD in community mental health
      settings. The new adaptation is for patients in community addiction treatment
      with co-occurring PTSD and substance use disorders. In this study, 5 community
      therapists delivered the CBT for PTSD. Outcome data are available on 11 patients
      who were assessed at baseline, post-CBT treatment, and at a 3-month follow-up
      post-treatment. Primary outcomes were substance use, PTSD severity, and
      retention, of which all were favorable for patients receiving the CBT for PTSD.

PMID- 19395180
TI  - The impact of email recruitment on our understanding of college smoking.
AB  - Email recruitment is growing in popularity; however, this convenience sampling
      method may yield very different results from prior convenience sampling methods.
      Participants in the current study were 825 undergraduate students, 446 recruited
      through a campus wide email and 379 recruited through Introductory Psychology
      courses, who completed an on-line survey on smoking and health. Outcomes varied
      significantly by group. Introductory Psychology students reported higher smoker
      self-concept, more pros of smoking, and were more likely to view smoking as a
      method of negative affect reduction. The current study suggests that recruitment
      method can bias our understanding of smoking behaviors among college students.

PMID- 19395181
TI  - Atypical E-cadherin expression in cell clusters overlying focally disrupted
      mammary myoepithelial cell layers: implications for tumor cell motility and
      invasion.
AB  - Our recent studies showed that cell clusters overlying focal myoepithelial cell
      layer disruptions (FMCLD) had a significantly higher rate of ER negativity,
      genetic instabilities, and expression of invasion-related genes than adjacent
      cells within the same duct. This study attempted to determine if these cells
      would show aberrant E-cadherin expression, which imparts greater propensity for
      cell motility and invasion. Consecutive sections from breast tumors with a high
      frequency of FMCLD were double-immunostained for E-cadherin and a panel of
      related markers. The E-cadherin mRNA levels in cells overlying FMCLD and adjacent
      cells within the same duct were compared using real-time PCR. Nearly all the cell
      clusters overlying FMCLD were strongly immunoreactive for E-cadherin, whereas
      their adjacent counterparts within the same duct were largely negative. Cell
      clusters overlying FMCLD were generally arranged as tongue-like projections,
      "puncturing" deep into the stroma or tube-like structures that often contained
      red blood cells. The sub-cellular localization of E-cadherin in the above
      structures, however, was primarily cytoplasmic. The mRNA level of E-cadherin in
      cell clusters overlying FMCLD was significantly higher than that in adjacent
      cells within the same duct. These findings suggest that aberrant expression of E
      cadherin may contribute to cell motility and invasion.

PMID- 19395182
TI  - Baseline utilization of breast radiotherapy before institution of the Medicare
      practice quality reporting initiative.
AB  - PURPOSE: In 2007, Medicare implemented the Physician Quality Reporting Initiative
      (PQRI), which provides financial incentives to physicians who report their
      performance on certain quality measures. PQRI measure #74 recommends radiotherapy
      for patients treated with conservative surgery (CS) for invasive breast cancer.
      As a first step in evaluating the potential impact of this measure, we assessed
      baseline use of radiotherapy among women diagnosed with invasive breast cancer
      before implementation of PQRI. METHODS AND MATERIALS: Using the SEER-Medicare
      data set, we identified women aged 66-70 diagnosed with invasive breast cancer
      and treated with CS between 2000 and 2002. Treatment with radiotherapy was
      determined using SEER and claims data. Multivariate logistic regression tested
      whether receipt of radiotherapy varied significantly across clinical, pathologic,
      and treatment covariates. RESULTS: Of 3,674 patients, 94% (3,445) received
      radiotherapy. In adjusted analysis, the presence of comorbid illness (odds ratio
      [OR] 1.69; 95% confidence interval [CI], 1.19-2.42) and unmarried marital status
      were associated with omission of radiotherapy (OR 1.65; 95% CI, 1.22-2.20). In
      contrast, receipt of chemotherapy was protective against omission of radiotherapy
      (OR 0.25; 95% CI, 0.16-0.38). Race and geographic region did not correlate with
      radiotherapy utilization. CONCLUSIONS: Utilization of radiotherapy following CS
      was high for patients treated before institution of PQRI, suggesting that at most
      6% of patients could benefit from measure #74. Further research is needed to
      determine whether institution of PQRI will affect radiotherapy utilization.

PMID- 19395183
TI  - Long-term results of brachytherapy for carcinoma of the penis confined to the
      glans (N- or NX).
AB  - PURPOSE: To analyze the results of exclusive interstitial low-dose-rate
      brachytherapy (BT) for squamous cell carcinoma (SCC) of the penis, strictly
      confined to the glans. METHODS AND MATERIALS: A total of 144 patients with SSC of
      the glans penis were treated with BT. Inguinal nodal dissection was performed in
      19% of patients (all N-). After circumcision, BT was performed using the
      hypodermic needle technique. Median iridium length per patients was 24 cm (range,
      4-108) and median dose was 65 Gy (range, 37-75). Median treated volume was 22
      cm(3) (range, 5-110) and median reference isodose rate was 0.4 Gy/h (range, 0.2
      1.2). RESULTS: Median follow-up was 5.7 years (range, 0.5-29). The 10-year penile
      recurrence, inguinal lymph node recurrence, and inguinal nodal metastasis rates
      were: 20% (CI 95%, 11-29), 11% (CI 95%, 5-17), and 6% (CI 95%, 2-10),
      respectively. After salvage treatment, 86% patients with local failure were in a
      complete remission at last follow-up. The 10-year probability of avoiding penile
      surgery (for complication or local recurrence) was 72% (CI 95%, 62-82). The 10
      year cancer-specific survival rate was 92% (CI 95%, 87-97). Diameter of tumor
      significantly increased the risk of recurrence (p = 0.02). The 10-year painful
      ulceration and stenosis risk rates were: 26% (CI 95%, 17-35) and 29% (CI 95%, 18
      40), respectively. Seven patients required excision for necrosis. Treated volume
      and reference isodose rate significantly increased the risk of complications.
      CONCLUSION: BT is an effective conservative treatment for SCC confined to the
      glans. Salvage local treatment is effective. Dose rate should be limited to
      decrease toxicity.

PMID- 19395184
TI  - Interval to testosterone recovery after hormonal therapy for prostate cancer and
      risk of death.
AB  - PURPOSE: To assess whether the risk of death is associated with the time to
      testosterone recovery (TTR) after radiotherapy (RT) and hormonal therapy (HT) for
      prostate cancer (PCa). PATIENTS AND METHODS: Between 1995 and 2001, 206 men with
      localized, unfavorable-risk PCa were randomized to receive RT or RT plus 6 months
      of HT. A multivariate postrandomization Cox regression analysis was used to
      assess whether the TTR in years was associated with the risk of death after
      adjusting for the known prognostic factors, age, Adult Comorbidity Evaluation-27
      score, and the use of HT for recurrence. RESULTS: Of the 102 men randomized to
      receive RT and HT, 57 (56%) had a TTR of >2 years, and none of these men had died
      of PCa after a median follow-up of 7.6 years. As the TTR increased, the risk of
      death decreased significantly (adjusted hazard ratio, 0.60; 95% confidence
      interval, 0.43-0.84; p = .003). A significant interaction was noted between the
      TTR and the comorbidity score (p = .002). The survival estimates were similar (p
      = 0.17) across the TTR values in men with moderate to severe comorbidity;
      however, these estimates increased significantly (p < .001) with decreasing PCa
      specific mortality (p = .006) as the TTR increased in men with no or minimal
      comorbidity. CONCLUSION: The results of our study have shown that a longer TTR
      after RT plus 6 months of HT for unfavorable-risk PCa is associated with a lower
      risk of death in men with no or minimal comorbidity.

PMID- 19395185
TI  - Intraoperative spillage of favorable histology wilms tumor cells: influence of
      irradiation and chemotherapy regimens on abdominal recurrence. A report from the
      National Wilms Tumor Study Group.
AB  - PURPOSE: We undertook this study to determine (1) the frequency with which
      spilled tumor cells of favorable histology produced intra-abdominal disease in
      patients treated with differing chemotherapy regimens and abdominal radiation
      therapy (RT) and (2) the patterns of relapse and outcomes in such patients.
      METHODS AND MATERIALS: The influence of RT dose (0, 10, and 20 Gy), RT fields
      (flank, whole abdomen), and chemotherapy with dactinomycin and vincristine (2
      drugs) vs. added doxorubicin (three drugs) on intra-abdominal tumor recurrence
      rates was analyzed by logistic regression in 450 patients. Each patient was
      considered at risk for two types of failure: flank and subdiaphragmatic beyond
      flank recurrence, with the correlation between the two outcomes accounted for in
      the analyses. RESULTS: The crude odds ratio for the risk of recurrence relative
      to no RT was 0.35 (0.15-0.78) for 10Gy and 0.08 (0.01-0.58) for 20Gy. The odds
      ratio for the risk of recurrence for doxorubicin to two drugs after adjusting for
      RT was not significant. For Stage II patients (NWTS-4), the 8-year event rates
      with and without spillage, respectively, were 79% and 87% for relapse-free
      survival (p = 0.07) and 90% and 95% for overall survival (p = 0.04). CONCLUSIONS:
      Irradiation (10 Gy or 20 Gy) reduced abdominal tumor recurrence rates after tumor
      spillage. Tumor spillage in Stage II patients reduced relapse-free survival and
      overall survival, but only the latter was of statistical significance. These data
      provide a basis for assessing the risks vs. benefits when considering treatment
      for children with favorable histology Wilms tumor and surgical spillage.

PMID- 19395186
TI  - Survival following radiation and androgen suppression therapy for prostate cancer
      in healthy older men: implications for screening recommendations.
AB  - PURPOSE: The U.S. Preventive Services Task Force has recommended against
      screening men over 75 for prostate cancer. We examined whether older healthy men
      could benefit from aggressive prostate cancer treatment. METHODS AND MATERIALS:
      206 men with intermediate to high risk localized prostate cancer randomized to 70
      Gy of radiation (RT) or RT plus 6 months of androgen suppression therapy (RT+AST)
      constituted the study cohort. Within subgroups stratified by Adult Comorbidity
      Evaluation-27 comorbidity score and age, Cox multivariable analysis was used to
      determine whether treatment with RT+AST as compared with RT was associated with a
      decreased risk of death. RESULTS: Among healthy men (i.e., with mild or no
      comorbidity), 78 were older than the median age of 72.4 years, and in this
      subgroup, RT+AST was associated with a significantly lower risk of death on
      multivariable analysis (adjusted hazard ratio = 0.36 (95% CI=0.13-0.98), p =
      0.046, with significantly lower 8-year mortality estimates of 16.5% vs. 41.4% (p
      = 0.011). Conversely, among men with moderate or severe comorbidity, 24 were
      older than the median age of 73, and in this subgroup, treatment with RT+AST was
      associated with a higher risk of death (adjusted hazard ratio = 5.2 (1.3-20.2), p
      = 0.018). CONCLUSION: In older men with mild or no comorbidity, treatment with
      RT+AST was associated with improved survival compared with treatment with RT
      alone, suggesting that healthy older men may derive the same benefits from
      prostate cancer treatment as younger men. We therefore suggest that prostate
      cancer screening recommendations should not be based on strict age cutoffs alone
      but should also take into account comorbidity.

PMID- 19395187
TI  - Is biochemical response more important than duration of neoadjuvant hormone
      therapy before radiotherapy for clinically localized prostate cancer? An analysis
      of the 3- versus 8-month randomized trial.
AB  - PURPOSE: To ascertain whether biochemical response to neoadjuvant androgen
      deprivation therapy (ADT) before radiotherapy (RT), rather than duration, is the
      critical determinant of benefit in the multimodal treatment of localized prostate
      cancer, by comparing outcomes of subjects from the Canadian multicenter 3- vs 8
      month trial with a pre-RT, post-hormone PSA (PRPH-PSA) < or =0.1 ng/ml vs those
      >0.1 ng/ml. METHODS AND MATERIALS: From 1995 to 2001, 378 men with localized
      prostate cancer were randomized to 3 or 8 months of neoadjuvant ADT before RT. On
      univariate analysis, survival indices were compared between those with a PRPH-PSA
      < or =0.1 ng/ml vs >0.1 ng/ml, for all patients and subgroups, including
      treatment arm, risk group, and gleason Score. Multivariate analysis identified
      independent predictors of outcome. RESULTS: Biochemical disease-free survival
      (bDFS) was significantly higher for those with a PRPH-PSA < or =0.1 ng/ml
      compared with PRPH-PSA >0.1 ng/ml (55.3% vs 49.4%, p = 0.014). No difference in
      survival indices was observed between treatment arms. There was no difference in
      bDFS between patients in the 3- and 8-month arms with a PRPH-PSA < or =0.1 ng/ml
      nor those with PRPH-PSA >0.1 ng/ml. bDFS was significantly higher for high-risk
      patients with PRPH-PSA < or =0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (57.0%
      vs 29.4%, p = 0.017). Multivariate analysis identified PRPH-PSA (p = 0.041),
      Gleason score (p = 0.001), initial PSA (p = 0.025), and T-stage (p = 0.003), not
      ADT duration, as independent predictors of outcome. CONCLUSION: Biochemical
      response to neoadjuvant ADT before RT, not duration, appears to be the critical
      determinant of benefit in the setting of combined therapy. Individually tailored
      ADT duration based on PRPH-PSA would maximize therapeutic gain, while minimizing
      the duration of ADT and its related toxicities.

PMID- 19395188
TI  - Retrospective comparison of external beam radiotherapy and radical prostatectomy
      in high-risk, clinically localized prostate cancer.
AB  - PURPOSE: Because of the lack of conclusive and well-conducted randomized studies,
      the optimal therapy for prostate tumors remains controversial. The aim of this
      study was to retrospectively compare the results of radical surgery vs. a
      conservative approach such as external beam radiotherapy (EBRT) plus androgen
      deprivation therapy using an intent-to-treat analysis on two pretreatment
      defined, concurrently treated, high-risk patient populations. METHODS AND
      MATERIALS: Between January 2003 and December 2007, 162 patients with high-risk
      prostate cancer underwent an EBRT plus androgen deprivation therapy program at
      the RT department of our institute. In the same period, 122 patients with the
      same high-risk disease underwent radical prostatectomy (RP) at the urologic
      department of our institute. Patients with adverse pathologic factors also
      underwent adjuvant EBRT with or without androgen deprivation therapy. The primary
      endpoint was freedom from biochemical failure. RESULTS: The two groups of high
      risk patients were homogeneous in terms of freedom from biochemical failure on
      the basis of the clinical T stage, biopsy Gleason score, and initial prostate
      specific antigen level. The median follow-up was 38.6 and 33.8 months in the EBRT
      and RP groups, respectively. The actuarial analysis of the freedom from
      biochemical failure showed a 3-year rate of 86.8% and 69.8% in the EBRT and RP
      group, respectively (p = .001). Multivariate analysis of the whole group revealed
      the initial prostate-specific antigen level and treatment type (EBRT vs. RP) as
      significant covariates. CONCLUSION: This retrospective intention-to-treat
      analysis showed a significantly better outcome after EBRT than after RP in
      patients with high-risk prostate cancer, although a well-conducted randomized
      comparison would be the best procedure to confirm these results.

PMID- 19395189
TI  - Comparison between hybrid direct aperture optimized intensity-modulated
      radiotherapy and forward planning intensity-modulated radiotherapy for whole
      breast irradiation.
AB  - PURPOSE: To investigate the planning efficiency and dosimetric characteristics of
      hybrid direct aperture optimized (hDAO) intensity-modulated radiotherapy (IMRT)
      compared with forward planning (FP)-IMRT for whole breast irradiation with two
      tangential beams. METHODS AND MATERIALS: A total of 15 patients with left-sided
      breast cancer, categorized with three different breast volumes, were selected for
      this study. All patients were treated with FP plans to 50 Gy in 25 fractions. The
      hDAO plans were created by combining two open fields with eight segments in two
      tangential beam directions and were inversely optimized. RESULTS: The FP and hDAO
      plans achieved similar breast coverage and sparing of critical organs. The volume
      of breast receiving 105% of the prescription dose was significantly smaller in
      the hDAO than in the FP plans: 25% vs. 63% (p = .008) for small, 22% vs. 57% (p =
      .005) for medium, and 28% vs. 53% (p = .005) for large breasts. Furthermore, the
      tumor cavity coverage was slightly better in the hDAO plans (92.4% vs. 90.9%).
      CONCLUSION: Compared with FP-IMRT, hDAO-IMRT provided dosimetric advantages,
      significantly reducing the size of the hot spot and slightly improving the
      coverage of the tumor cavity. In addition, hDAO-IMRT required less planning time
      and was less dependent on the planner's ability.

PMID- 19395190
TI  - Characterization of pancreatic tumor motion using cine MRI: surrogates for tumor
      position should be used with caution.
AB  - PURPOSE: Our current understanding of intrafraction pancreatic tumor motion due
      to respiration is limited. In this study, we characterized pancreatic tumor
      motion and evaluated the application of several radiotherapy motion management
      strategies. METHODS AND MATERIALS: Seventeen patients with unresectable
      pancreatic cancer were enrolled in a prospective internal review board-approved
      study and imaged during shallow free-breathing using cine MRI on a 3T scanner.
      Tumor borders were agreed on by a radiation oncologist and an abdominal MRI
      radiologist. Tumor motion and correlation with the potential surrogates of the
      diaphragm and abdominal wall were assessed. These data were also used to evaluate
      planning target volume margin construction, respiratory gating, and four
      dimensional treatment planning for pancreatic tumors. RESULTS: Tumor borders
      moved much more than expected. To provide 99% geometric coverage, margins of 20
      mm inferiorly, 10 mm anteriorly, 7 mm superiorly, and 4 mm posteriorly are
      required. Tumor position correlated poorly with diaphragm and abdominal wall
      position, with patient-level Pearson correlation coefficients of -0.18-0.43.
      Sensitivity and specificity of gating with these surrogates was also poor, at 53%
      68%, with overall error of 35%-38%, suggesting that the tumor may be underdosed
      and normal tissues overdosed. CONCLUSIONS: Motion of pancreatic tumor borders is
      highly variable between patients and larger than expected. There is substantial
      deformation with breathing, and tumor border position does not correlate well
      with abdominal wall or diaphragmatic position. Current motion management
      strategies may not account fully for tumor motion and should be used with
      caution.

PMID- 19395191
TI  - Time of decline in sexual function after external beam radiotherapy for prostate
      cancer.
AB  - PURPOSE: Erectile dysfunction is one of the most concerning toxicities for
      patients in the treatment of prostate cancer. The inconsistent evaluation of
      sexual function (SF) and limited follow-up data have necessitated additional
      study to clarify the rate and timing of erectile dysfunction after external beam
      radiotherapy (EBRT) for prostate cancer. METHODS AND MATERIALS: A total of 143
      men completed baseline data on SF before treatment and at the subsequent follow
      up visits. A total of 1187 validated SF inventories were analyzed from the study
      participants. Multiple domains of SF (sex drive, erectile function, ejaculatory
      function, and overall satisfaction) were analyzed for < or =8 years of follow-up.
      RESULTS: The median follow-up was 4.03 years. The strongest predictor of SF after
      EBRT was SF before treatment. For all domains of SF, the only statistically
      significant decrease in function occurred in the first 24 months after EBRT. SF
      stabilized 2 years after treatment completion, with no statistically significant
      change in any area of SF >2 years after the end of EBRT. CONCLUSION: These data
      suggest that SF does not have a continuous decline after EBRT. Instead, SF
      decreases maximally within the first 24 months after EBRT, with no significant
      changes thereafter.

PMID- 19395192
TI  - Acute toxicity in high-risk prostate cancer patients treated with androgen
      suppression and hypofractionated intensity-modulated radiotherapy.
AB  - PURPOSE: To report acute toxicity resulting from radiotherapy (RT) dose
      escalation and hypofractionation using intensity-modulated RT (IMRT) treatment
      combined with androgen suppression in high-risk prostate cancer patients. METHODS
      AND MATERIALS: Sixty patients with a histological diagnosis of high-risk
      prostatic adenocarcinoma (having either a clinical Stage of > or =T3a or an
      initial prostate-specific antigen [PSA] level of > or =20 ng/ml or a Gleason
      score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a
      Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions
      (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles.
      The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in
      25 fractions. The patients were treated with helical TomoTherapy-based IMRT and
      underwent daily megavoltage CT image-guided verification prior to each treatment.
      Acute toxicity scores were recorded weekly during RT and at 3 months post-RT,
      using Radiation Therapy Oncology Group acute toxicity scales. RESULTS: All
      patients completed RT and follow up for 3 months. The maximum acute toxicity
      scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI)
      toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30
      (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced
      after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11
      (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3
      months follow up. Only the V60 to the rectum correlated with the GI toxicity.
      CONCLUSION: Dose escalation using a hypofractionated schedule to the prostate
      with concurrent pelvic lymph node RT and long-term androgen suppression therapy
      is well tolerated acutely. Longer follow up for outcome and late toxicity is
      required.

PMID- 19395193
TI  - Benefit of radiation boost after whole-breast radiotherapy.
AB  - PURPOSE: To determine whether a boost to the tumor bed after breast-conserving
      surgery (BCS) and radiotherapy (RT) to the whole breast affects local control and
      disease-free survival. METHODS AND MATERIALS: A total of 1,138 patients with pT1
      to pT2 breast cancer underwent adjuvant RT at the University of Florence. We
      analyzed only patients with a minimum follow-up of 1 year (range, 1-20 years),
      with negative surgical margins. The median age of the patient population was 52.0
      years (+/-7.9 years). The breast cancer relapse incidence probability was
      estimated by the Kaplan-Meier method, and differences between patient subgroups
      were compared by the log rank test. Cox regression models were used to evaluate
      the risk of breast cancer relapse. RESULTS: On univariate survival analysis,
      boost to the tumor bed reduced breast cancer recurrence (p < 0.0001). Age and
      tamoxifen also significantly reduced breast cancer relapse (p = 0.01 and p =
      0.014, respectively). On multivariate analysis, the boost and the medium age (45
      60 years) were found to be inversely related to breast cancer relapse (hazard
      ratio [HR], 0.27; 95% confidence interval [95% CI], 0.14-0.52, and HR 0.61; 95%
      CI, 0.37-0.99, respectively). The effect of the boost was more evident in younger
      patients (HR, 0.15 and 95% CI, 0.03-0.66 for patients <45 years of age; and HR,
      0.31 and 95% CI, 0.13-0.71 for patients 45-60 years) on multivariate analyses
      stratified by age, although it was not a significant predictor in women older
      than 60 years. CONCLUSION: Our results suggest that boost to the tumor bed
      reduces breast cancer relapse and is more effective in younger patients.

PMID- 19395194
TI  - Late outcomes following hypofractionated conformal radiotherapy vs. standard
      fractionation for localized prostate cancer: a nonrandomized contemporary
      comparison.
AB  - PURPOSE: To study retrospectively late complications and biochemical control in
      patients treated with three-dimensional conformal external-beam radiotherapy for
      localized prostate cancer administered using hypofractionation vs. a standard
      fractionation regimen. The hypofractionation regimen (Hypo) was designed to avoid
      more late rectal reactions and to be done in half as many treatment sessions.
      METHODS AND MATERIALS: Eighty-nine nonrandomized patients chose Hypo delivered in
      20 fractions of 3 Gy (n = 52) or 3.15 Gy (n = 37) for a median overall treatment
      time of 33 days. One hundred thirty comparable patients were contemporaneously
      treated with standard fractionation to a median dose of 78 Gy delivered over 55
      days. The median follow-up time was 49 months (range, 24-73 months). RESULTS: The
      5-year actuarial biochemical control rates were 96%, 84%, and 85% for low-,
      medium-, and high-risk disease in the Hypo group, respectively. The respective
      rates in the standard fractionation group were 98%, 84%, and 87%, with no
      statistical difference between the two groups. The rate of rectal Grade 2-4
      complications was 5.5% in both treatment groups and of urinary Grade 2-4
      complications was 5.6% in the Hypo and 3% in the standard group (p = 0.36).
      Similarly, there were no statistical differences in the rate of late
      complications between patients treated with 3 Gy/fraction vs. 3.15 Gy/fraction.
      CONCLUSIONS: Our preliminary results showed that the Hypo regimen is feasible and
      does not reduce biochemical control compared with standard fractionation. The
      incidence of late complications was not increased when the tumor normalized total
      doses at 2Gy/fraction was increased from 77.1 to 83.7 Gy in patients treated with
      either 3 or 3.15 Gy/fraction in the Hypo group, respectively.

PMID- 19395195
TI  - Toxicity of three-dimensional conformal radiotherapy for accelerated partial
      breast irradiation.
AB  - PURPOSE: To assess the incidence and severity of late normal tissue toxicity
      using three-dimensional conformal radiotherapy to deliver accelerated partial
      breast irradiation. METHODS AND MATERIALS: A total of 60 patients were treated
      with three-dimensional conformal radiotherapy for accelerated partial breast
      irradiation. Treatment planning and delivery were in strict accordance with the
      technique and specified dose-volume constraints of the National Surgical Adjuvant
      Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol.
      Late toxicity was evaluated according to the Radiation Therapy Oncology Group
      grading schema. The cosmetic outcome was scored using the Harvard criteria.
      Univariate logistic regression analysis was performed to evaluate the correlation
      of dosimetric variables with outcome. RESULTS: At a median follow-up of 15
      months, moderate-to-severe late toxicity developed in 10% of patients. The most
      pronounced late toxicity was subcutaneous fibrosis: 25% Grade 2-4 and 8.3% Grade
      3-4. The modified planning tumor volume/whole breast volume ratio, ratio of the
      volume of breast tissue receiving 5%, 20%, 50%, and 80% of the prescription dose
      to the whole breast volume, and maximal dose within the breast correlated with
      the development of fibrosis (p = .10, p = .03, p = .04, p = .06, p = .09, and p =
      .046, respectively). The overall cosmetic outcome was good to excellent in 81.7%,
      fair in 11.7%, and poor in 6.7%. The presence of subcutaneous fibrosis, modified
      planning tumor volume/whole breast volume ratio, ratio of the volume of breast
      tissue receiving 5% and 20% of the prescription dose to the whole breast volume,
      and pathologic specimen volume correlated with the risk of a fair/poor cosmetic
      outcome (p < .001, p = .02, p = .05, p = .04, p = .01, respectively). CONCLUSION:
      The three-dimensional conformal radiotherapy technique for accelerated partial
      breast irradiation as specified in the National Surgical Adjuvant Breast and
      Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol resulted in a
      remarkably high rate of moderate-to-severe late normal tissue effects, despite
      the relatively brief follow-up period. The toxic events correlated clearly with
      several dose-volume parameters.

PMID- 19395196
TI  - Radioprotective effect of moderate wine consumption in patients with breast
      carcinoma.
AB  - PURPOSE: Given the high cost and side effects of radioprotective agents such as
      amifostine, attention has been focused on potentially equally effective but less
      expensive and toxic natural substances. We evaluated the potential
      radioprotective effects of wine in preventing skin toxicity in patients with
      breast cancer. METHODS AND MATERIALS: Before treatment, the medical history and
      habits of patients were assessed and the information recorded in their clinical
      folders. Patients were divided into three groups based on the dose/fractionation
      scheme used: control group, 60.4 Gy (standard technique); Modulated Accelerated
      Radiotherapy in Adjuvant treatment of breast cancer (MARA)-1 protocol group, 44
      Gy (concomitant boost to tumoral bed); and MARA-2 protocol group, 60 Gy
      (concomitant boost to tumoral bed). The impact of the following variables on
      acute skin toxicity was evaluated by chart review: radiotherapy protocol,
      planning target volume (PTV), comorbidity (e.g., hypertension and diabetes),
      hemoglobin level before therapy, adjuvant hormone therapy, adjuvant chemotherapy,
      cigarette smoking, and drinking habits. RESULTS: The study population consisted
      of 348 patients. More severe skin toxicity was significantly associated with the
      radiotherapy protocol (p < 0.001) and median PTV (p = 0.005). In addition, the
      incidence of acute toxicity of Grade 2 or greater was higher in patients without
      alcohol intake (38.4% vs. 22.3%, p = 0.021). The daily amount of alcohol intake
      also influenced the incidence of skin toxicity, with an incidence of 38.4% in
      patients with no wine intake, 31.8% in patients drinking half a glass per day,
      13.6% in patients drinking one glass per day, and 35.0% in patients drinking two
      glasses per day. Multivariate analysis showed that wine intake, PTV, and
      radiotherapy protocol were all significantly correlated with acute toxicity.
      CONCLUSIONS: Our results indicate that wine may have a radioprotective effect;
      however, prospective studies are needed to confirm this beneficial effect of wine
      and its components.

PMID- 19395197
TI  - Tumor localization using cone-beam CT reduces setup margins in conventionally
      fractionated radiotherapy for lung tumors.
AB  - PURPOSE: To determine whether setup margins can be reduced using cone-beam
      computed tomography (CBCT) to localize tumor in conventionally fractionated
      radiotherapy for lung tumors. METHODS AND MATERIALS: A total of 22 lung cancer
      patients were treated with curative intent with conventionally fractionated
      radiotherapy using daily image guidance with CBCT. Of these, 13 lung cancer
      patients had sufficient CBCT scans for analysis (389 CBCT scans). The patients
      underwent treatment simulation in the BodyFix immobilization system using four
      dimensional CT to account for respiratory motion. Daily alignment was first done
      according to skin tattoos, followed by CBCT. All 389 CBCT scans were
      retrospectively registered to the planning CT scans using automated soft-tissue
      and bony registration; the resulting couch shifts in three dimensions were
      recorded. RESULTS: The daily alignment to skin tattoos with no image guidance
      resulted in systematic (Sigma) and random (sigma) errors of 3.2-5.6 mm and 2.0
      3.5 mm, respectively. The margin required to account for the setup error
      introduced by aligning to skin tattoos with no image guidance was approximately 1
      1.6 cm. The difference in the couch shifts obtained from the bone and soft-tissue
      registration resulted in systematic (Sigma) and random (sigma) errors of 1.5-4.1
      mm and 1.8-5.3 mm, respectively. The margin required to account for the setup
      error introduced using bony anatomy as a surrogate for the target, instead of
      localizing the target itself, was 0.5-1.4 cm. CONCLUSION: Using daily CBCT soft
      tissue registration to localize the tumor in conventionally fractionated
      radiotherapy reduced the required setup margin by up to approximately 1.5 cm
      compared with both no image guidance and image guidance using bony anatomy as a
      surrogate for the target.

PMID- 19395198
TI  - A statistical evaluation of rules for biochemical failure after radiotherapy in
      men treated for prostate cancer.
AB  - PURPOSE: The "PSA nadir + 2 rule," defined as any rise of 2 ng/ml above the
      current prostate-specific antigen (PSA) nadir, has replaced the American Society
      for Therapeutic Radiology and Oncology (ASTRO) rule, defined as three consecutive
      PSA rises, to indicate biochemical failure (BF) after radiotherapy in patients
      treated for prostate cancer. We propose an original approach to evaluate BF rules
      based on the PSAdt as the gold standard rule and on a simulation process allowing
      us to evaluate the BF rules under multiple settings (different frequency,
      duration of follow-up, PSA doubling time [PSAdt]). METHODS AND MATERIALS: We
      relied on a retrospective, population-based cohort of individuals identified by
      the Connecticut Tumor Registry and treated for localized prostate cancer with
      radiotherapy. We estimated the 470 underlying true PSA trajectories, including
      the PSAdt, using a Bayesian hierarchical changepoint model. Next, we simulated
      realistic, sophisticated data sets that accurately reflect the systematic and
      random variations observed in PSA series. We estimated the sensitivity and
      specificity by comparing the simulated PSA series to the underlying true PSAdt.
      RESULTS: For follow-up of more than 3 years, the specificity of the PSA nadir + 2
      rule was systematically greater than that of the ASTRO criterion. In few
      settings, the nadir + 2 rule had a lower sensitivity than the ASTRO. The PSA
      nadir + 2 rule appeared less dependent on the frequency and duration of follow-up
      than the ASTRO. CONCLUSIONS: Our results provide some refinements to earlier
      findings as the BF rules were evaluated according to various parameters. In most
      settings, the PSA nadir + 2 rule outperforms the ASTRO criterion.

PMID- 19395199
TI  - Radicality of resection and survival after multimodality treatment is influenced
      by subsite of locally recurrent rectal cancer.
AB  - PURPOSE: To analyze results of multimodality treatment in relation to subsite of
      locally recurrent rectal cancer (LRRC). METHOD AND MATERIALS: A total of 170
      patients with LRRC who underwent treatment between 1994 and 2008 were studied.
      The basic principle of multimodality treatment was preoperative
      (chemo)radiotherapy, intended radical surgery, and intraoperative radiotherapy.
      The subsites of LRRC were classified as presacral, posterolateral,
      (antero)lateral, anterior, anastomotic, or perineal. Subsites were related to
      radicality of the resection, local re-recurrence rate, distant metastasis rate,
      and cancer-specific survival. RESULTS: R0 resections were achieved in 54% of the
      patients, and 5-year cancer-specific survival was 40.5%. The worst outcomes were
      seen in presacral LRRC, with only 28% complete resections and 19% 5-year survival
      (p = 0.03 vs. other subsites). Anastomotic LRRC resulted in the most favorable
      outcomes, with 77% R0 resections and 60% 5-year survival (p = 0.04). Generally,
      if a complete resection was achieved, survival improved, except in posterolateral
      LRRC. Local re-recurrence and metastasis rate were lowest in anastomotic LRRC.
      CONCLUSIONS: Classification of the subsite of LRRC is a predictor of potentially
      resectable and consequently curable disease. Treatment of posterior LRRC imposes
      poor results, whereas anastomotic LRRC location shows superior results.

PMID- 19395200
TI  - Quantifying interfraction and intrafraction tumor motion in lung stereotactic
      body radiotherapy using respiration-correlated cone beam computed tomography.
AB  - PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective treatment for
      medically inoperable Stage I non-small-cell lung cancer. However, changes in the
      patient's breathing patterns during the course of SBRT may result in a geographic
      miss or an overexposure of healthy tissues to radiation. However, the precise
      extent of these changes in breathing pattern is not well known. We evaluated the
      inter- and intrafractional changes in tumor motion amplitude (DeltaM) over an
      SBRT course. METHODS AND MATERIALS: Eighteen patients received image-guided SBRT
      delivered in three fractions; this therapy was done with abdominal compression in
      four patients. For each fraction, cone beam computed tomography (CBCT) was
      performed for tumor localization (+/- 3-mm tolerance) and then repeated to
      confirm geometric accuracy. Additional CBCT images were acquired at the midpoint
      and end of each SBRT fraction. Respiration-correlated CBCT (rcCBCT)
      reconstructions allowed retrospective assessment of inter- and intrafractional
      DeltaM by a comparison of tumor displacements in all four-dimensional CT and
      rcCBCT scans. The DeltaM was measured in mediolateral, superior-inferior, and
      anterior-posterior directions. RESULTS: A total of 201 rcCBCT images were
      analyzed. The mean time from localization of the tumor to the end-fraction CBCT
      was 35 +/- 7 min. Compared with the motion recorded on four-dimensional CT, the
      mean DeltaM was 0.4, 1.0, and 0.4 mm, respectively, in the mediolateral, superior
      inferior, and anterior-posterior directions. On treatment, the observed DeltaM
      was, on average, <1 mm; no DeltaM was statistically different with respect to the
      initial rcCBCT. However, patients in whom abdominal compression was used showed a
      statistically significant difference (p < 0.05) in the variance of DeltaM with
      respect to the initial rcCBCT in the superior-inferior direction. CONCLUSIONS:
      The inter- and intrafractional DeltaM that occur during a course of lung SBRT are
      small. However, abdominal compression causes larger variations in the time spent
      on the treatment couch and in the inter- and intrafractional DeltaM values.

PMID- 19395201
TI  - Adult supratentorial low-grade glioma: long-term experience at a single
      institution.
AB  - PURPOSE: To report the long-term follow-up of a cohort of adult patients with
      supratentorial low-grade glioma treated at a single institution. METHODS AND
      MATERIALS: A cohort of 145 adult patients treated at the London Regional Cancer
      Program between 1979 and 1995 was reviewed. RESULTS: With a median follow-up of
      105 months, the median progression-free survival was 61 months (95% confidence
      interval, 53-77), and the median overall survival was 118 months (95% confidence
      interval, 93-129). The 10- and 20-year progression-free and overall survival rate
      was 18% and 0% and 48% and 22%, respectively. Cox regression analysis confirmed
      the importance of age, histologic type, presence of seizures, Karnofsky
      performance status, and initial extent of surgery as prognostic variables for
      overall and cause-specific survival. Function among long-term survivors without
      tumor progression was good to excellent for most patients. CONCLUSION: Low-grade
      glioma is a chronic disease, with most patients dying of their disease. However,
      long-term survival with good function is possible. Survival is determined
      primarily by the disease factors with selection and timing of adjuvant treatments
      having less influence on outcome.

PMID- 19395202
TI  - Hyperfractionated Accelerated Radiotherapy (HART) for anaplastic thyroid
      carcinoma: toxicity and survival analysis.
AB  - PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive
      cancers, and the current protocol of hyperfractionated accelerated radiotherapy
      was initiated to improve survival while limiting toxicities. METHODS AND
      MATERIALS: All patients with ATC from 1991 to 2002 were accrued and received
      megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in
      twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. RESULTS: Thirty-one
      patients were accrued with a median age of 69 years, and 55% were women.
      Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68%
      received radical radiotherapy alone. Local control data were available for 27
      patients: 22% had a complete response, 26% had a partial response, 15% showed
      progressive disease, and 37% showed static disease. Median overall survival for
      all 31 patients was 70 days (95% confidence interval, 40-99). There was no
      significant difference in median survival between patients younger (70 days) and
      older than 70 years (42 days), between men (70 days) and women (49 days), and
      between patients receiving postoperative radiotherapy (77 days) and radical
      radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56%
      patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%.
      CONCLUSION: The current protocol failed to offer a significant survival benefit,
      was associated with severe toxicities, and thus was discontinued. There is a
      suggestion that younger patients with operable disease have longer survival, but
      this would require a larger study to confirm it.

PMID- 19395203
TI  - AUDIT and its abbreviated versions in detecting heavy and binge drinking in a
      general population survey.
AB  - BACKGROUND: The aim of this study was to define optimal cut points for the
      Alcohol Use Disorders Identification Test (AUDIT) and its abbreviated versions
      (AUDIT-C, AUDIT-QF, and AUDIT-3), and to evaluate how effectively these
      questionnaires detect heavy drinking in the general population. METHODS: The
      study population consisted of a sub-sample of the National FINRISK Study. A
      stratified random sample of 3216 Finns, aged 25-64, was invited to a health
      check. Of these, 1851 (57.6%) completed the AUDIT and participated in person in
      the Timeline Followback (TLFB) interview regarding their alcohol consumption. The
      TLFB-based definition of heavy drinking was used as a primary gold standard (for
      males > or =16 standard drinks average in a week or > or =7 drinks at least once
      a month; for females, respectively, > or =10 and > or =5 drinks). Areas under
      receiving operating characteristics curves (AUROCs), sensitivities and
      specificities were used to compare the performance of the tests. RESULTS AND
      CONCLUSIONS: The AUDIT and its abbreviated versions are valid for detecting heavy
      drinking also in a general population sample. However, performance seems to vary
      between the different versions and accuracy of each test is achieved only by
      using tailored cut points according to gender. The AUDIT and AUDIT-C are
      effective for both males and females. The optimal cut points for males were found
      to be >/=7 or 8 for AUDIT and > or =6 for AUDIT-C. Among females the optimal cut
      points were found to be > or =5 for AUDIT and > or =4 for AUDIT-C. The study also
      indicates that AUDIT-QF among females and AUDIT-3 among males are relatively
      effective. The cut points for detecting all heavy drinkers (including binge
      drinkers without exceeding weekly thresholds) were lower than for detecting heavy
      drinkers excluding those who are only binge drinkers.

PMID- 19395204
TI  - Availability and capacity of substance abuse programs in correctional settings: A
      classification and regression tree analysis.
AB  - OBJECTIVE TO BE ADDRESSED: The purpose of this study was to investigate the
      structural and organizational factors that contribute to the availability and
      increased capacity for substance abuse treatment programs in correctional
      settings. We used classification and regression tree statistical procedures to
      identify how multi-level data can explain the variability in availability and
      capacity of substance abuse treatment programs in jails and probation/parole
      offices. METHODS: The data for this study combined the National Criminal Justice
      Treatment Practices (NCJTP) Survey and the 2000 Census. The NCJTP survey was a
      nationally representative sample of correctional administrators for jails and
      probation/parole agencies. The sample size included 295 substance abuse treatment
      programs that were classified according to the intensity of their services: high,
      medium, and low. The independent variables included jurisdictional-level
      structural variables, attributes of the correctional administrators, and program
      and service delivery characteristics of the correctional agency. RESULTS: The two
      most important variables in predicting the availability of all three types of
      services were stronger working relationships with other organizations and the
      adoption of a standardized substance abuse screening tool by correctional
      agencies. For high and medium intensive programs, the capacity increased when an
      organizational learning strategy was used by administrators and the organization
      used a substance abuse screening tool. Implications on advancing treatment
      practices in correctional settings are discussed, including further work to test
      theories on how to better understand access to intensive treatment services. This
      study presents the first phase of understanding capacity-related issues regarding
      treatment programs offered in correctional settings.

PMID- 19395205
TI  - Signs of fetal brain sparing are not related to umbilical cord blood gases at
      birth.
AB  - BACKGROUND: Fetal chronic hypoxia leads to centralization of circulation in order
      to spare the vital organs brain, adrenals and the heart. This can be documented
      by Doppler ultrasound. Increased blood velocity in the fetal middle cerebral
      artery (MCA) is an acknowledged sign of centralization of circulation in chronic
      hypoxia, and is called brain sparing. AIM: Our aim was to assess the relationship
      between signs of brain sparing in the MCA and umbilical cord blood gases at
      birth. STUDY DESIGN: A prospective study. SUBJECTS: Singleton 57 high-risk
      pregnancies (outcome was compared with 21 normal pregnancies). METHODS: MCA
      Doppler was performed within 24 h of elective caesarean section in high-risk
      pregnancies. Umbilical cord blood gases were analysed at birth. MAIN OUTCOME
      MEASURES: Cord blood gases were related to signs of centralization of fetal
      circulation in the MCA. RESULTS: No correlation between signs of brain sparing in
      the MCA and cord blood gases. Apgar score at 5'<7 was seen in three newborns, but
      only one of these had antenatal signs of brain sparing. Newborns with antenatal
      brain sparing were admitted more often (p<0.04) and had a longer duration of stay
      in NICU (p<0.03) compared to newborns without brain sparing. CONCLUSION:
      Decreased pulsatility index in MCA is an acknowledged sign of fetal
      centralization of circulation during chronic hypoxia. However, signs of brain
      sparing are not related to cord blood gases at birth, which might suggest that
      redistribution of fetal circulation can maintain normal blood gases for a long
      time during chronic hypoxia.

PMID- 19395206
TI  - Analysis of fatty acids in ecstasy tablets.
AB  - Fatty acids are the basis of so-called stearates which are frequently used as
      lubricants in the production of ecstasy tablets. Being a product added at the
      initial tablet production step its composition does not change once the
      compression is performed. The analysis of fatty acids can therefore provide
      useful information for a drug intelligence purpose. In this context an
      appropriate analytical method was developed to improve results already obtained
      by routine analyses. Considering the small quantity of such fatty acids in
      ecstasy tablets (approximately 3%) the research focussed on their extraction and
      concentration. Two different procedures were tested: (1) liquid/liquid extraction
      using dichloromethane followed by derivatisation and (2) in situ
      transesterification using bortrifluoride. Analyses were performed by GC-MS. The
      two procedures were optimized and applied to eight ecstasy seizures, in order to
      choose one of the procedures for its application to a large ecstasy sample set.
      They were compared by considering the number of peaks detected and sample amount
      needed, reproducibility and other technical aspects.

PMID- 19395207
TI  - Blood kinetics of ethyl glucuronide and ethyl sulphate in heavy drinkers during
      alcohol detoxification.
AB  - Studies of ethyl glucuronide (EtG) blood kinetics have so far been performed on
      healthy volunteers with ingestion of low to moderate doses of ethanol. These data
      are not necessarily transferable to heavy drinkers where the consumed doses of
      ethanol are much higher. The aim of this study was to investigate the
      pharmacokinetics of EtG and ethyl sulphate (EtS) in blood in heavy drinkers after
      termination of alcohol ingestion. Sixteen patients from an alcohol withdrawal
      clinic were included directly after admission. Time of end of drinking, estimated
      daily intake of ethanol (EDI) and medical history were recorded. Three to five
      blood samples over 20-43 h were collected from each patient subsequent to
      admission. The median EDI was 172 g (range 60-564). The first sample was
      collected median 2.5 h after end of drinking (range 0.5-23.5). Two patients had
      levels of EtG and EtS below LOQ in all samples, the first collected 19.25 and
      23.5 h after cessation of drinking, respectively. Of the remaining 14 patients,
      one subject, suffering from both renal and hepatic disease, showed concentrations
      of EtG and EtS substantially higher than the rest of the material. This patient's
      initial value of EtG was 17.9 mg/L and of EtS 5.9 mg/L, with terminal elimination
      half lives of 11.9 h for EtG and 12.5 h for EtS. Among the remaining 13 patients,
      the initial median values were 0.7 g/L (range 0-3.7) for ethanol, 1.7 mg/L (range
      0.1-5.9) for EtG and 0.9 mg/L (range 0.1-1.9) for EtS. Elimination occurred with
      a median half-life of 3.3 h for EtG (range 2.6-4.3) and 3.6 h for EtS (range 2.7
      5.4). In conclusion, elimination of EtG in heavy drinkers did not significantly
      differ from healthy volunteers, and EtS appeared to have similar elimination
      rate. In the present work, there was one exception to this, and we propose that
      this could be explained by the patient's renal disease, which would delay
      excretion of these conjugated metabolites.

PMID- 19395208
TI  - Comparison of body height estimation using bipeds or cylinders.
AB  - A well-known method for performing body height measurements on images uses a 3D
      model of the crime scene, projected onto the image. In the 3D model the height of
      persons on images can be measured using either cylinders or bipeds (3D
      humanoids). The study compares the performance of taking body height measurements
      on the basis of both tools. To this, measurements were compared to actual heights
      in a pilot study that involved images of four perpetrators, one not standing
      straight. Differences in systematic and random measurement error were studied,
      showing no significant difference in behavior between the methods. Systematic
      measurement error is regularly occurring for the biped method as well (two out of
      four cases), so bipeds are not preferable to cylinders in this respect. Next to
      this, random measurement errors for the two methods seem comparable. Since the
      fitting of bipeds is more labor-intensive, there seems to be limited sense in
      preferring this method to using cylinders to measure body heights in 3D models.

PMID- 19395209
TI  - [Epidemiology of acute bacterial meningitis in adult patients in France].
AB  - In 2006, the number of bacterial meningitis cases was estimated at 1375
      (2.23/100,000). The leading pathogens involved in adult meningitis were,
      according to frequency, Streptococcus pneumoniae, Neisseria meningitidis,
      Listeria monocytogenes, Streptococcus agalactiae, and Haemophilus influenzae. The
      overall mortality rate averaged 20%, higher among patients with pneumococcal
      meningitis or in individuals over 65 years of age. Sequels were observed in 30%
      of cases and more frequent after pneumococcal meningitis. A decrease in
      susceptibility to antibiotics was reported for N. meningitidis, S. pneumoniae and
      H. influenzae. Generalized vaccination of children less than two years of age
      with H. influenzae type b conjugate vaccine has lead to a dramatic decrease in
      adult H. influenza meningitis. The few cases involved almost exclusively non
      typeable strains, presenting in 12% of cases, a modified penicillin binding
      protein leading to a decreased susceptibility to aminopenicillins. Decreased
      susceptibility to amoxicillin was observed in 30% of meningococcal isolates, but
      all strains remained susceptible to parenteral third generation cephalosporins.
      Resistances to rifampicin or to ciprofloxacin, recommended in meningococcal
      meningitis prophylaxis, were unusual, but had to be documented. Finally, the
      proportion of pneumococcal strains with decreased susceptibility to beta-lactams
      has decreased since 2002. In adult meningitis, pneumococcal isolates with
      decreased susceptibility to penicillin, amoxicillin, and cefotaxime or
      ceftriaxone accounted for 37, 18, and 4% of cases respectively. It should be
      noted that for these isolates, no parenteral third generation cephalosporins MIC
      was above 2mg/l. Resistance to rifampin was very unusual and all pneumococcal
      isolates were fully susceptible to glycopeptides.

PMID- 19395210
TI  - Methicillin-resistant Staphylococcus aureus among a network of French private
      sector community-based-medical laboratories.
AB  - OBJECTIVE: The aim of this study was to estimate the frequency of methicillin
      resistant Staphylococcus aureus (MRSA) strains in the French community and the
      proportion of Panton-Valentine (PVL)-MRSA. DESIGN: A cross-sectional study was
      made during a 3-month period in 2003 through a network of private-sector,
      community-based medical laboratories selected throughout France: the Labville
      network. Each MRSA isolate was included and characterized by French National
      Reference Center for Staphylococci. The total number of S. aureus isolates was
      also collected. RESULTS: Among the 283 patients infected or colonized by MRSA,
      166 (59%) were considered as healthcare-associated, 14 (5%) as nursing-associated
      and 39 (14%) as community-acquired. The proportion of methicillin resistance
      among S. aureus was 14%. Taking into account the sampling design, the incidence
      of MRSA cases in French outpatients was estimated to be 0.50 [CI95%: 0.41-0.60]
      per 10,000 inhabitants. The molecular analysis confirmed that 80.6% belong to the
      Lyon clone, the most prevalent hospital MRSA clone spreading in France and 10.6%
      to a closely related clone. An emerging MRSA clone containing the tst1 gene was
      detected in six patients and the PVL-positive ST80 clone only in one, 22-year
      old, patient. CONCLUSION: Most of MRSA cases diagnosed in the community in
      France, in 2003, were elderly with specific risk factors and harbored hospital
      strains. The prevalence of PVL-MRSA remained low.

PMID- 19395211
TI  - MR imaging of the cisternal segment of the posterior group of cranial nerves:
      neurovascular relationships and abnormal changes.
AB  - OBJECTIVE: To evaluate the detailed anatomic features, neurovascular
      relationships of the cisternal segment of the posterior group of cranial nerves
      (PGCN: IX, X, XI, XII); to evaluate the utility of magnetic resonance (MR) in
      demonstrating the PGCN with disorders caused by abnormal compression related to
      artery or tumor. METHODS: A total of 59 volunteers, 12 patients with abnormal
      symptom in the PGCN underwent three-dimensional (3D) Fourier transformation
      constructive interference in steady-state (CISS) MR imaging, and 22 of these
      volunteers and 12 patients also underwent MR angiography in which a time-of
      flight (TOF) sequence was used to further distinguish the PGCN from the adjacent
      blood vessels. Anatomical features, neurovascular relationships of the PGCN in 59
      volunteers and abnormal changes in 12 patients caused by neurovascular
      compression or tumor were observed from multi-planar reconstruction (MPR) images,
      cryomicrotome section and 3D-CISS MR imaging of cranial cadaver were used to
      testify the PGCN displayed in 59 volunteers. RESULTS: 3D-CISS MR imaging depicted
      the proximal cisternal segment of the cranial nerves complex (CN IX, X, XI) at
      the oblique axial, sagittal planes in 100% (118/118), 99% (117/118) of 118 sides;
      CNXII in the oblique axial, sagittal planes in 90% (106/118), 91% (107/118) of
      118 sides. At the sagittal planes, the CN IX, X, XI were found parallel to each
      other in the cisternal segment in 45.2% (53/117) of 117 sides, gathering into a
      bundle of nerves complex before entering the jugular foramen (JF) in 54.7%
      (64/117) of 117 sides. VAs were blood vessels more often identified, they were
      found to be in contact with the PGCN in 28.0% (33/118) of 118 sides, and not in
      contact in 72.0% (85/118) of 118 sides. 3D-CISS MR imaging of volunteers revealed
      the similar result corresponding to cryomicrotome section and 3D-CISS MR imaging
      of cranial cadaver. Twelve patients with abnormal changes in the PGCN were all
      displayed well, among them 8 were pressed by arteries, 1 by arachnoid cyst, and 3
      caused by tumors. CONCLUSION: Use of 3D-CISS sequence enables accurate
      identification of the cisternal segment of the PGCN, neurovascular relationships
      and abnormal changes caused by neurovascular compression or tumor.

PMID- 19395212
TI  - A fully automated algorithm under modified FCM framework for improved brain MR
      image segmentation.
AB  - Automated brain magnetic resonance image (MRI) segmentation is a complex problem
      especially if accompanied by quality depreciating factors such as intensity
      inhomogeneity and noise. This article presents a new algorithm for automated
      segmentation of both normal and diseased brain MRI. An entropy driven homomorphic
      filtering technique has been employed in this work to remove the bias field. The
      initial cluster centers are estimated using a proposed algorithm called histogram
      based local peak merger using adaptive window. Subsequently, a modified fuzzy c
      mean (MFCM) technique using the neighborhood pixel considerations is applied.
      Finally, a new technique called neighborhood-based membership ambiguity
      correction (NMAC) has been used for smoothing the boundaries between different
      tissue classes as well as to remove small pixel level noise, which appear as
      misclassified pixels even after the MFCM approach. NMAC leads to much sharper
      boundaries between tissues and, hence, has been found to be highly effective in
      prominently estimating the tissue and tumor areas in a brain MR scan. The
      algorithm has been validated against MFCM and FMRIB software library using MRI
      scans from BrainWeb. Superior results to those achieved with MFCM technique have
      been observed along with the collateral advantages of fully automatic
      segmentation, faster computation and faster convergence of the objective
      function.

PMID- 19395213
TI  - Determination of bencycloquidium bromide in human urine using weak cation
      exchange solid-phase extraction and LC-ESI-MS: Method validation and application
      to kinetic study of urinary excretion.
AB  - A sensitive LC-ESI-MS method has been developed and validated for the
      determination of bencycloquidium bromide (BCQB) in human urine samples. The
      method utilized a solid-phase extraction (SPE) procedure, choosing carboxy propyl
      phase (CBA) as the extracting sorbent for purification of BCQB, with better
      baseline and higher selectivity achieved. Sample preparation by this method
      yielded very good and consistent mean recovery of above 94.5%. Another major
      benefit of the present method was the high detectability, with a lower limit of
      quantification (LLOQ) of 0.02ng/ml. The developed method was successfully applied
      to determine BCQB in human urine, and was proved to be suitable for use in Phase
      I clinical pharmacokinetic study of BCQB.

PMID- 19395214
TI  - Factors affecting cleavage at aspartic residues in model decapeptides.
AB  - The aqueous stability of four decapeptides was investigated in an acetate buffer
      at different pHs (4.0-5.5) and temperatures (25, 40, and 60 degrees C). The four
      decapeptides share the following common sequence-Tyr-Ala-Arg-Asp-Aaa-Pro-Leu-Gly
      Tyr-Thr, where Aaa represents Gln, Pro, Lys, or Leu. The major degradation
      pathway was found to be the cleavage at Asp-Aaa. The degradation process fits
      well the first-order kinetics. The cleavage of the decapeptide containing Asp-Pro
      was faster than that of other three decapeptides. A strong pH dependence of
      cleavage was observed for all decapeptides, especially when pH was <5. Three out
      of four decapeptides showed a clear Arrhenius temperature dependency whereas Asp
      Pro-containing peptide did not.

PMID- 19395215
TI  - Quantitation of the tacrine analogue octahydroaminoacridine in human plasma by
      liquid chromatography-tandem mass spectrometry.
AB  - A rapid and sensitive method based on liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) has been developed for the determination of
      octahydroaminoacridine in human plasma using tramadol as internal standard
      (I.S.). Sample preparation involved pH adjustment with sodium carbonate followed
      by solvent extraction with dichloromethane:ethyl ether (40:60, v/v).
      Chromatographic separation was achieved on a Venusil MP-C18 column (5 microm, 100
      mm x 4.6mm) using acetonitrile:10mM ammonium acetate:formic acid (30:70:1, v/v/v)
      as mobile phase. Detection utilized an API 4000 system operated in the positive
      ion mode with multiple reaction monitoring of the analyte at m/z 203.1-->175.1
      and of the I.S. at m/z 264.1-->58.0. The method was linear in the range 0.01-10
      ng/ml with a lower limit of quantitation of 0.0 1ng/ml. Intra- and inter-day
      precisions measured as relative standard deviation were <3.15% and <5.01%,
      respectively. The method was successfully applied to a pharmacokinetic study
      involving oral administration of a tablet containing 4 mg octahydroaminoacridine
      succinate to healthy volunteers. Pharmacokinetic parameters for
      octahydroaminoacridine include C(max) 1.19+/-0.53 ng/ml, T(max) 0.77+/-0.17 h,
      AUC(0-t) 3.42+/-1.01 ng h/ml and t(1/2) 2.89+/-0.56 h.

PMID- 19395216
TI  - Apropos "Evaluation of dengue nonstructural protein 1 antigen strip for the rapid
      diagnosis of patients with dengue infection".

PMID- 19395217
TI  - Value of 2 IgG avidity commercial tests used alone or in association to date
      toxoplasmosis contamination.
AB  - Toxoplasmosis acquired during pregnancy exposes the fetus to congenital
      toxoplasmosis. Avidity tests are commonly used to date time of infection to
      evaluate the fetal risk and to offer prenatal diagnosis. This study evaluated and
      compared 2 commercial avidity tests: Platelia Toxo IgG Avidity (Bio-Rad, Marnes
      la Coquette, France) and Liaison(R) Toxo IgG Avidity II (Diasorin, Saluggia,
      Italy) kits. In complement, a study of specific IgG and IgM in the 2 systems was
      carried out. Sensitivity and specificity of the avidity tests were 94.4% and
      87.8% for the Liaison(R) and 91.3% and 98.5% for the Platelia methods,
      respectively. Percentages of complete discrepancies, partial discrepancies, and
      agreement between both tests were 1.1%, 23.6%, and 75.3%, respectively. Moreover,
      the combination of both avidity tests may be useful in some cases. Indeed, that
      strategy permitted to confirm without delay a chronic toxoplasmosis in 23 cases
      and avoid treatment in these pregnant women.

PMID- 19395218
TI  - Detection of pathogenic Leptospira spp. through TaqMan polymerase chain reaction
      targeting the LipL32 gene.
AB  - Rapid diagnosis of leptospirosis, through culture and/or serology, can be
      difficult without proper expertise and is often delayed because of the length of
      time required to obtain results. In this study, we developed a real-time
      polymerase chain reaction (PCR) assay using a TaqMan probe targeting lipL32,
      which is present only in pathogenic Leptospira spp. Using Leptospira interrogans
      serovar Icterohaemorrhagiae DNA, the lower limit of detection was found to be 20
      genomic equivalents/reaction with a 95% cutoff value. The assay detected
      pathogenic Leptospira strains, but not intermediately pathogenic or nonpathogenic
      strains. When testing the assay on spiked clinical specimens, whole blood and
      plasma were better specimens for detecting the same initial number of leptospires
      compared with serum from clotted and centrifuged blood. Leptospira spiked at the
      same concentration was better detected in centrifuged urine. This real-time PCR
      assay with high specificity and sensitivity may prove to be a rapid method for
      diagnosing acute leptospirosis.

PMID- 19395219
TI  - Macrolide resistance in Streptococcus pyogenes: prevalence, resistance
      determinants, and emm types.
AB  - To investigate the antimicrobial resistance trends and the distribution of emm
      types of group A streptococci (GAS), we examined 1160 clinical isolates of GAS
      collected between 2003 and 2006. Susceptibilities to commonly used antimicrobial
      agents were determined by Etest, and macrolide resistance genes were detected by
      polymerase chain reaction (PCR). GAS isolates were typed by polymerase chain
      reaction PCR and sequencing of emm gene. The rates of resistance to erythromycin
      (ERY), clindamycin, azithromycin, tetracycline, and chloramphenicol were 14.9%,
      1.4%, 14.9%, 18.9%, 0.6%, respectively. None of the isolates exhibited resistance
      to penicillin, ceftriaxone, linezolid, moxifloxacin, rifampicin, or vancomycin.
      Macrolide resistance increased from 12.1% in 2003 to 18.8% in 2006 (P = 0.02). Of
      173 ERY-resistant GAS isolates, 93 (53.7%) harbored the mefA gene, 70 (40.4%) the
      ermA, and 10 (5.8%) the ermB. Eighty percent of the observed emm types are
      covered by the proposed 26-valent GAS vaccine. Among 173 ERY-resistant isolates,
      the predominant emm types were 12 (19.5%), 77 (17.9%), and 4 (16.8%), and among
      770 ERY-susceptible isolates, the predominant types were 1 (18.8%), 12 (17.5%),
      28 (13.8%). The observed antimicrobial resistance trends and the distribution of
      specific emm types have implications in guiding empiric therapy and in developing
      vaccine strategies to prevent GAS infections.

PMID- 19395220
TI  - Development of a 1-step cell-based assay for cost-effective screening of
      antiviral drugs for vaccinia virus.
AB  - We report a 1-step assay to screen antiviral substances combining the
      simultaneous application of cells, virus sample, and drug to 96-well plates. The
      results were obtained within 26 h when vaccinia virus plaques were counted or
      virus-induced cytopathic effect was measured. This fast cost-effective procedure
      may be used for other cytopathic viruses and is suitable to 1st screening tests.

PMID- 19395222
TI  - The effect of physician-patient collaboration on patient adherence in non
      psychiatric medicine.
AB  - OBJECTIVE: Factors contributing to treatment adherence are poorly understood but
      the physician-patient interaction is one factor that is known to affect patient
      adherence. METHODS: This meta-analysis systematically reviewed the published
      literature to determine the magnitude of the relationships between physician
      patient collaboration and patient adherence. RESULTS: A statistically significant
      weighted mean effect size of M(d)=0.145 from 48 published studies indicated
      better physician-patient collaboration is associated with better patient
      adherence. The relationship between collaboration and adherence was sustained for
      pediatric and adult populations, chronic and acute conditions, and primary
      physician and specialists. CONCLUSION: These results emphasize the need for
      physician-patient collaboration within the medical consultation. PRACTICE
      IMPLICATIONS: The inclusion of the patient's perspective during the consultation
      is essential to obtaining cooperation once the patient has left the physician's
      office.

PMID- 19395221
TI  - The HPV vaccine and the media: how has the topic been covered and what are the
      effects on knowledge about the virus and cervical cancer?
AB  - OBJECTIVE: In June 2006, the first vaccine for HPV was approved by the FDA and
      media coverage about the topic increased significantly. This study sought to
      explore the nature of the coverage and whether knowledge about HPV was affected
      by it. METHODS: A content analysis, including 321 news stories from major
      newspapers, the AP wire and television news networks was conducted. A monthly RDD
      recruited Internet survey with a national sample (n=3323) was used to assess
      changes in population knowledge. RESULTS: Twenty-three percent of stories did not
      mention the sexually transmitted nature of the disease and 80% left out
      information about the need for continued cervical cancer screening after
      vaccination. Exposure to health-related media content was significantly
      associated with knowledge about HPV, even controlling for baseline knowledge
      (OR=1.62, 95% CI=1.12-2.35). CONCLUSIONS: Changes in the volume of coverage over
      time were associated with knowledge about HPV, but the content analysis reveals
      that many of the stories were missing important information. PRACTICE
      IMPLICATIONS: Clinicians must consider the potential media source patients are
      using for HPV-related information in order to correct inaccurate or incomplete
      information that could affect health behavior.

PMID- 19395223
TI  - The relationship between health literacy and knowledge improvement after a
      multimedia type 2 diabetes education program.
AB  - OBJECTIVE: Multimedia diabetes education programs (MDEP) have the potential to
      improve communication and education of those with low health literacy. We
      examined the effect of a MDEP targeted to patients with low literacy on knowledge
      and assessed the association between literacy and knowledge improvement. METHODS:
      We showed the MDEP to 190 patients recruited from clinics at a federally
      qualified health center and an academic health center. We measured diabetes
      knowledge before and after viewing the MDEP. RESULTS: Seventy-nine percent of
      patients had adequate literacy, 13% marginal, and 8% inadequate literacy.
      Patients across all literacy levels had significant increases in knowledge scores
      after viewing the MDEP (p-value<0.001). Patients with inadequate literacy learned
      significantly less after the MDEP (adjusted beta-coefficient=-2.3, SE=0.70)
      compared to those with adequate literacy. CONCLUSIONS: A MDEP designed for those
      with low literacy significantly increased diabetes knowledge across literacy
      levels. However, the MDEP did not overcome the learning gap between patients with
      low and high literacy. PRACTICE IMPLICATIONS: A literacy appropriate MDEP may be
      an effective way to teach patients about diabetes. Combining the MDEP with other
      education methods may improve comprehension and learning among those with low
      literacy. Research is needed to identify which characteristics of low-literate
      patients influence the ability to learn health information. Identifying these
      factors and incorporating solutions into a diabetes education intervention may
      help bridge the learning gap related to literacy status.

PMID- 19395225
TI  - The impact of patients' participation on physicians' patient-centered
      communication.
AB  - OBJECTIVE: The goal of this study is to add to a small, but growing body of
      research exploring how patients' communication style affects physicians'
      communication. In particular, we examine how patients' active participation
      (e.g., asking questions, providing information) affects physicians' use of
      patient-centered communication. METHODS: The same 25 physicians were observed
      interacting with high and low participation patients. High participation was
      defined as the frequency of information seeking/verifying, information provision,
      assertive utterances, and expressing concerns. On average, physicians interviewed
      2.56 high participation patients and 3.44 low participation patients. Transcripts
      of the interviews were coded for physicians' patient-centered communication. High
      and low patient participation interviews were then compared using nested ANOVAs.
      RESULTS: When interacting with high participation patients, physicians engaged in
      significantly more patient-centered communication overall than when interacting
      with low participation patients. Analyses on separate components of patient
      centeredness indicated that physicians engaged in significantly more exploring of
      patients' disease and illness, but did not engage in significantly more
      understanding of the whole person or finding of common ground. CONCLUSION:
      Patients who actively participate in medical interviews influence physicians to
      adopt a more patient-centered style of communication.

PMID- 19395224
TI  - Verbal communication among Alzheimer's disease patients, their caregivers, and
      primary care physicians during primary care office visits.
AB  - OBJECTIVE: Primary care visits of patients with Alzheimer's disease (AD) often
      involve communication among patients, family caregivers, and primary care
      physicians (PCPs). The objective of this study was to understand the nature of
      each individual's verbal participation in these triadic interactions. METHODS: To
      define the verbal communication dynamics of AD care triads, we compared verbal
      participation (percent of total visit speech) by each participant in
      patient/caregiver/PCP triads. Twenty-three triads were audio taped during a
      routine primary care visit. Rates of verbal participation were described and
      effects of patient cognitive status (MMSE score, verbal fluency) on verbal
      participation were assessed. RESULTS: PCP verbal participation was highest at 53%
      of total visit speech, followed by caregivers (31%) and patients (16%). Patient
      cognitive measures were related to patient and caregiver verbal participation,
      but not to PCP participation. Caregiver satisfaction with interpersonal treatment
      by PCP was positively related to caregiver's own verbal participation.
      CONCLUSION: Caregivers of AD patients and PCPs maintain active, coordinated
      verbal participation in primary care visits while patients participate less.
      PRACTICE IMPLICATIONS: Encouraging verbal participation by AD patients and their
      caregivers may increase the AD patient's active role and caregiver satisfaction
      with primary care visits.

PMID- 19395226
TI  - Development and initial validation of a heart disease knowledge questionnaire for
      people with rheumatoid arthritis.
AB  - OBJECTIVE: To develop and validate two parallel versions of the Heart Disease
      Fact Questionnaire-Rheumatoid Arthritis (HDFQ-RA), a modified and RA-specific
      version of the HDFQ. METHODS: The questionnaire was composed of generic questions
      from the original HDFQ with additional RA-specific questions added. Cognitive
      interviewing was performed and the questionnaire piloted to generate two parallel
      questionnaires. For psychometric validation, 130 patients with RA completed the
      questionnaires at baseline and 2 weeks later. RESULTS: Parallel form reliability
      of both questionnaires was established; the median score for both questionnaires
      was 9/13 with no statistical difference in scores. Kuder-Richardson-20 formula
      was 0.65 and 0.67 for both questionnaires. Test-retest stability showed constant
      median scores of 9/13 and no statistical difference in scores between baseline
      and follow-up. Known groups comparison revealed that patients who had self
      educated themselves about heart disease, or who were taking CVD medications, had
      significantly higher scores on the questionnaires. CONCLUSION: The two parallel
      forms of the HDFQ-RA have been shown to be equivalent measures of CVD knowledge
      and evidence supporting their reliability and validity is presented. PRACTICE
      IMPLICATIONS: The HDFQ-RA is an appropriate tool for application in clinical and
      research settings, e.g., assessing novel educational interventions or tracking
      participants' progress on an education course.

PMID- 19395227
TI  - Caregiver health literacy and adherence to a daily multi-vitamin with iron
      regimen in infants.
AB  - OBJECTIVE: To determine whether or not limited caregiver health literacy is
      associated with adherence to a daily multi-vitamin with iron regimen in infants.
      METHODS: 110 caregiver/infant dyads were enrolled in a prospective study to
      assess the relationship between caregiver health literacy and adherence to a
      daily multi-vitamin with iron regimen for infants. Households were contacted
      biweekly over a 3-month period. Adherence was based upon caregiver report. High
      adherence, our primary outcome, was defined as the administration of the multi
      vitamin with iron on 5-7 days over the past week. RESULTS: As measured by the
      Short Test of Functional Health Literacy in Adults (S-TOFHLA), 18% of caregivers
      had limited health literacy skills. Caregivers with limited health literacy
      skills were more likely to have higher adherence than caregivers with adequate
      health literacy, after adjusting for a number of possible confounding variables
      (AOR=2.13; 95% 1.20-3.78). CONCLUSION: Caregivers with limited health literacy
      were twice as likely to report high adherence to a daily multi-vitamin with iron
      regimen in infants as caregivers with adequate health literacy in adjusted
      analysis. PRACTICE IMPLICATIONS: Health literacy may exert a differential
      influence on adherence depending upon the complexity of the desired health
      behavior.

PMID- 19395228
TI  - Understanding metaphor to facilitate emotional expression during a chronic
      disease self-management course.
AB  - OBJECTIVE: This study was designed to understand emotional expression as an
      element of the chronic disease self-management course (CDSMC). METHODS:
      Interpretive phenomenological analysis (IPA) was used to analyse a qualitative
      interview data set in which 10 lay-tutors described their perceptions of
      emotional expression during a CDSMC. The accounts were used to develop an
      interpretive phenomenological account. RESULTS: Tutors suggest that people on a
      CDSMC are often unaware of their own emotional state and lack the vocabulary for
      expression. Tutors use metaphorical language to help Course participants to
      identify their own feelings and construct meaning of their illness experiences.
      'Off-loading' and 'feeling blue' are used to help them find the expressions to
      talk about their emotions and release their feelings. CONCLUSION: Tutors use
      metaphoric terms as a framework for the understanding of emotional states that
      Course participants often find 'difficult to label'. The analogous structure of
      metaphor helps with the understanding of inner feelings and provides expressive
      phrases for dialogue that can lead to emotional relief. PRACTICE IMPLICATIONS:
      This study provides important considerations that could be applied when training
      CDSMC tutors to help facilitate emotional understanding and expression.

PMID- 19395229
TI  - [Spondylarthropathy with Behcet's disease: response to infliximab].

PMID- 19395230
TI  - [Cutaneous fistula of a liver hydatid cyst].

PMID- 19395231
TI  - [Acute hypercalcemia and multiple squamous cell carcinomas arising in
      hidradenitis suppurativa].

PMID- 19395232
TI  - [Cryptogenic cerebral infarction: from classification to concept].
AB  - Since the foundations laid by Sacco and Mohr in 1989, from the Stroke data bank,
      cryptogenic infarctions have had a predominant place among the causes of ischemic
      strokes. In that study, they accounted for approximately 40% of the stroke
      causes. Cryptogenic infarctions are infarctions without a defined cause, despite
      a complete work-up; they differ from infarctions of undetermined causes, which
      may involve overlapping causes or an incomplete investigation. The size of this
      group will probably shrink as knowledge advances. Patent foramen ovale (PFO),
      with or without a septal aneurysm, is more frequent in patients with a
      cryptogenic infarction. Transesophageal echocardiography is the reference
      examination for screening for these abnormalities. A meta-analysis of several
      case-control studies showed a significant association between PFO and stroke in
      subjects younger than 55 years. For now, these septal abnormalities constitute a
      risk factor but not a cause. Complex aortic atheroma affecting area upstream of
      the left subclavian artery may be a source of cerebral embolisms in some
      conditions. The prevalence of this disease increases with age. It is identified
      most frequently in patients older than 60 years with a cryptogenic infarction.
      The thickness of the atheromatous plaque determines whether it is a risk factor
      or a cause. Recent stroke classifications do not consider carotid atheromatous
      lesions less than 50% to be a source of ischemic stroke. Nonetheless some studies
      identify moderate stenosis of the carotid artery more frequently in infarctions
      of unknown causes than in other categories. The increased risk of cerebral
      infarction when parents and homozygous twins have a history of stroke suggests
      that there may be genetic causes that have not yet been detected. An unknown
      genetic cause would thus be included in the infarctions of unknown causes. A
      recent study tested for Fabry disease in young patients with a cryptogenic
      infarction: 4.9% of the men and 2.4% of the women had a functional mutation of
      the alpha-galactosidase gene. These findings must be confirmed. Some studies
      suggest an association between cryptogenic infarction and hereditary
      thrombophilias. Nonetheless the risk attributable to these thrombophilic
      disorders is slight and the discovery may be only a coincidence. The work
      described above shows the importance of stratification in the identification of
      stroke causes: age older or younger than 55/60 years, type of interatrial
      abnormality (PFO and aneurysms of the interatrial septum), type of atheroma of
      the aortic arch (more or less than 4mm). They also show the difficulty involved
      in attributing cause to an identified abnormality: is carotid stenosis of less
      than 50% a marker of atherosclerosis or also a cause of stroke? To continue
      improving our understanding of the mechanisms of strokes, new investigational
      techniques are under evaluation. They include magnetic resonance imaging (MRI),
      computed tomographic angiography (CT), positron emission tomography (PET) of
      carotid plaque and of the aortic arch, transcranial Doppler, cardiac recording by
      telemetry, and even new biological assays.

PMID- 19395233
TI  - Rasch analysis of the Bruininks-Oseretsky Test of Motor Proficiency-Second
      Edition in intellectual disabilities.
AB  - The Bruininks-Oseretsky Test of Motor Proficiency-Second Edition (BOT-2) is
      widely used to assess motor skills for both clinical and research purposes;
      however, its validity has not been adequately assessed in intellectual
      disabilities (ID). This study used partial credit Rasch model to examine the
      measurement properties of the BOT-2 among 446 children and adolescents with ID
      aged 4-18 years. Seventeen items were identified as problematic in the Rasch
      modeling. After removal of these items, the appropriateness of the response
      categories was examined in the 36 remaining items. Where the item response
      categories failed to express an increasing level of the trait (disordered
      thresholds), collapsing adjacent categories was performed to address this issue.
      After rescoring most items, items in each composite of the revised BOT-2 showed
      good fit to the Rasch model and demonstrated excellent reliability (range 0.90
      0.97). No differential item functioning was detected with respect to age and
      gender. The ability of the revised composites to differentiate between mild
      versus moderate to severe ID was better than those of the original BOT-2. Items
      from the manual coordination and strength and agility composites were well
      targeted to the sample, whereas items from fine manual control and body
      coordination composites were mostly targeted at the lower levels of ability in
      these domains. Items of higher difficulty may be supplemented to increase the
      range of ability levels of the people to whom these two composites can be applied
      with precision.

PMID- 19395234
TI  - Coordinated machine learning and decision support for situation awareness.
AB  - Domains such as force protection require an effective decision maker to maintain
      a high level of situation awareness. A system that combines humans with neural
      networks is a desirable approach. Furthermore, it is advantageous for the
      calculation engine to operate in three learning modes: supervised for initial
      training and known updating, reinforcement for online operational improvement,
      and unsupervised in the absence of all external signaling. An Adaptive Resonance
      Theory based architecture capable of seamlessly switching among the three types
      of learning is discussed that can be used to help optimize the decision making of
      a human operator in such a scenario. This is followed by a situation assessment
      module.

PMID- 19395235
TI  - Adaptive learning via selectionism and Bayesianism, Part II: the sequential case.
AB  - Animals increase or decrease their future tendency of emitting an action based on
      whether performing such action has, in the past, resulted in positive or negative
      reinforcement. An analysis in the companion paper [Zhang, J. (2009). Adaptive
      learning via selectionism and Bayesianism. Part I: Connection between the two.
      Neural Networks, 22(3), 220-228] of such selectionist style of learning reveals a
      resemblance between its ensemble-level dynamics governing the change of action
      probability and Bayesian learning where evidence (in this case, reward) is
      distributively applied to all action alternatives. Here, this equivalence is
      further explored in solving the temporal credit-assignment problem during the
      learning of an action sequence ("operant chain"). Naturally emerging are the
      notion of secondary (conditioned) reinforcement predicting the average reward
      associated with a stimulus, and the notion of actor-critic architecture involving
      concurrent learning of both action probability and reward prediction. While both
      are consistent with solutions provided by contemporary reinforcement learning
      theory (Sutton & Barto, 1998) for optimizing sequential decision-making under
      stationary Markov environments, we investigate the effect of action learning on
      reward prediction when both are carried out concurrently in any on-line scheme.

PMID- 19395236
TI  - The KIV model of intentional dynamics and decision making.
AB  - Human cognition performs granulation of the seemingly homogeneous temporal
      sequences of perceptual experiences into meaningful and comprehensible chunks of
      fuzzy concepts and behaviors. These knowledge granules are stored and
      consequently accessed during action selection and decisions. A dynamical approach
      is presented here to interpret experimental findings using K (Katchalsky) models.
      In the K model, meaningful knowledge is repetitiously created and processed in
      the form of sequences of oscillatory patterns of neural activity distributed
      across space and time. These patterns are not rigid but flexible and
      intermittent; soon after they arise through phase transitions, they dissipate.
      Computational implementations demonstrate the operation of the model based on the
      principles of intentional brain dynamics.

PMID- 19395237
TI  - Computed tomography morphology of the mandibular ramus at the lingual plane in
      patients with mandibular hyperplasia.
AB  - This study investigated the specific morphology of the mandibular ramus at the
      lingual plane in patients with mandibular hyperplasia using spiral computed
      tomography. The subjects were 25 patients with mandibular hyperplasia undergoing
      sagittal split ramus osteotomy and there were 20 patients without dentofacial
      deformities in the control group. The thickness of the mandible, diameter of the
      inner mandibular canal, width of the buccal bone marrow space, and the width of
      the buccal cortex and lingual cortex were measured at the lingual plane, which
      contained the lowest point of the mandibular foramen. The average thickness of
      the mandible was 8.5 mm in prognathic patients and 9.6mm in control patients. The
      average width of the buccal bone marrow space in mandibular hyperplasia patients
      was 1.5 mm and 2.5 mm in control patients. The mandibular ramus in patients with
      mandibular hyperplasia was thinner and the width of the buccal bone marrow space
      was smaller than in the control patients. The width of the buccal bone marrow
      space and the thickness of the mandible were significantly positively correlated.

PMID- 19395238
TI  - Lichen sclerosus of the oral mucosa: clinicopathological features of six cases.
AB  - Lichen sclerosus is a chronic inflammatory mucocutaneous disease, rarely
      involving the mouth. There are only 20 well-documented cases of oral lichen
      sclerosus reported in the English-language literature. This report describes the
      clinicopathological features of 6 cases of oral lichen sclerosus; 5 in women.
      There were 12 lesions, mainly on the lips (50%) and buccal mucosa (25%). The
      affected areas appeared as irregular whitish patches, harder than the surrounding
      tissue. Half of the patients were symptomatic and presented with no associated
      skin and/or genital lesions. All cases were biopsied, and histopathological
      features were evaluated using hematoxylin-eosin and Verhoeff's stains, S-100
      immunohistochemical reaction and transmission electron microscopy. Management of
      the oral lesions consisted of surgical excision, intralesional triamcinolone
      acetonide, oral colchicine, and regular follow-up. There is no effective curative
      treatment, but there are some options for patient management; and colchicine may
      be considered an additional choice.

PMID- 19395240
TI  - Effects of cognitive remediation therapies on psychotic symptoms and cognitive
      complaints in patients with schizophrenia and related disorders: a randomized
      study.
AB  - BACKGROUND: Cognitive remediation therapy (CRT) has proven to be effective in
      treating cognitive deficits in schizophrenia. The current study aimed to assess
      the efficacy of CRT on psychotic symptoms and cognitive complaints. METHODS: We
      contrasted the changes in symptoms and cognitive complaints in patients with
      schizophrenia and related disorders who received 2 novel CRTs, one targeting
      mental state attribution, and the other, mental flexibility, compared with a
      control group given treatment as usual. Twenty-four patients with schizophrenia
      and related disorders were pseudo-randomly assigned to 1 of 3 groups. Psychotic
      symptoms and subjective complaints about their cognitive deficits were evaluated
      twice in each group, before and after therapy. Scores obtained pre- and post
      therapy were compared between the groups. RESULTS: The therapies were well
      tolerated by the participants, and no one dropped out of the study. Symptoms
      decreased after therapy, but not in the control group. The mental flexibility
      group showed the most improvement. Moreover, patients in this group described a
      subjective diminution of their cognitive deficits. CONCLUSIONS: Our results
      demonstrate that CRT can be useful to reduce clinical symptoms while they suggest
      an impact of CRT on cognitive complaints in patients with schizophrenia.

PMID- 19395239
TI  - Effect of age on cognitive sequelae following early life seizures in rats.
AB  - PURPOSE: Clinical studies have suggested that seizures in newborns are more
      damaging than seizures occurring in older children. However, these studies are
      difficult to interpret for a variety of factors including differing etiologies of
      seizures across ages. Animal studies can provide insights into the question of
      whether age of seizure onset in children is a factor in cognitive outcome.
      METHODS: To evaluate the effect of age on seizure-induced cognitive impairment we
      subjected rats to 50 seizures from postnatal days P0-P10 or P15-P25. As adults
      the rats were studied in the Morris water maze, radial-arm water maze, open
      field, and active avoidance. To assess synaptic strength and network excitatory
      and inhibitory function animals were evaluated with long-term potentiation (LTP)
      and paired-pulse facilitation/inhibition. RESULTS: Compared to controls, both
      groups of rats with recurrent seizures were impaired in spatial memory in both
      water maze tests, had altered activity in the open field, and did not differ from
      controls in active avoidance. Rats with recurrent seizures had impaired LTP but
      showed no deficits in paired-pulse facilitation or inhibition. While rats with
      later onset showed a trend to worse performance than rats with earlier seizures,
      the differences were not substantial. CONCLUSIONS: Recurrent seizures during
      development are associated with long-term behavioral deficits in learning, memory
      and activity level as well as impaired synaptic efficiency. Age of seizure onset
      was not a strong predictor of outcome.

PMID- 19395241
TI  - Effects and side effects of antipsychotic treatment in schizophrenia: pros and
      cons of available self-rating scales.
AB  - INTRODUCTION: To support clinical practice as well as clinical research, self
      rating scales have been developed to evaluate the effects and side effects of
      antipsychotic treatment. The aim of this study is to compare the psychometric
      properties and other characteristics of frequently used self-rating scales, and
      also to study their relationship to subjective quality of life. METHOD: Four self
      rating scales designed to evaluate the treatment effects of antipsychotics were
      identified through a MEDLINE and cross-references search: The Drug Attitude
      Inventory (DAI-10), The Liverpool University Neuroleptic Side Effect Rating Scale
      (LUNSERS), Subjective Well-being to Neuroleptics (SWN) and the recently developed
      Subjects' Reaction to Antipsychotics questionnaire (SRA). Three hundred and
      twenty patients with schizophrenia who were treated with antipsychotics completed
      these questionnaires, including a quality of life instrument, the WHO-QoLBREF.
      RESULTS: The self-rating scales differed in scope, number of items and subscales
      (total and subscale scores), but showed an acceptable internal reliability
      (Cronbach's alphas varying between .64 and .93) except for the DAI-10 (.52), and
      all were easy to complete (in less than 20 min). They did not strongly correlate
      with each other, except for the LUNSERS and SRA undesired experiences subscale
      (r=.68, p<.01). All correlations with quality of life were statistically
      significant, but were especially so for the SWN (.78, p<.01). CONCLUSION:
      Clinicians interested in the experience of the effects and side effects of
      antipsychotic medication in their patients are well advised to carefully consider
      the pros and cons of the available rating scales. They differ with respect to
      their internal reliability, concurrent and conceptual validity, as well as with
      respect to desired and undesired effects, aspects of quality of life, and
      attribution to medication. The choice also depends on its intended use, whether
      in clinical practice or in research or in both.

PMID- 19395242
TI  - Aberrant DNA methylation in skin diseases.
AB  - Epigenetic mechanisms are involved in regulating cell growth and differentiation
      without inducing changes in the gene sequence. The main epigenetic mechanisms
      include DNA methylation, histone modification, and microRNA. Recent studies
      indicate that aberrant DNA methylation is a common feature of many human
      disorders, including cancer, autoimmune diseases, heart diseases, skin diseases,
      and others. Skin diseases comprise various diseases that have a complex etiology
      and pathogenesis, including genetics and acquired factors such as environment and
      diet. These acquired factors often have pathogenic effects through modification
      of DNA and histones, of which DNA methylation is the most common mechanism.
      Aberrant DNA methylation has been demonstrated in skin diseases, including skin
      tumors and autoimmune-related skin disorders. Herein, we review the role of DNA
      methylation in the pathogenesis of skin diseases.

PMID- 19395243
TI  - Serum high molecular weight adiponectin levels are decreased in psoriasis
      patients.

PMID- 19395244
TI  - Delusions and dorso-medial frontal cortex volume in first-episode schizophrenia:
      a voxel-based morphometry study.
AB  - Of the few studies that have directly investigated the neuroanatomical correlates
      of delusions in patients with recent-onset schizophrenia, a number have
      paradoxically reported a positive correlation between delusion severity and
      regional grey matter volume. In order to explore this relationship, 31 patients
      with first-episode schizophrenia (FES) underwent a clinical interview and a T1
      weighted structural MRI scan. Patients' scores on the Delusions subscale of the
      Positive and Negative Syndrome Scale were correlated with the volume of every
      voxel in their grey matter images in SPM99. Patients' delusion scores were found
      to correlate with the volume of a cluster of voxels located in the dorso-medial
      frontal cortex, centred on the medial frontal gyrus. Post-hoc analysis revealed
      that this 'region-of-correlation' was volumetrically reduced in the FES patients
      relative to a group of 21 matched healthy controls. The results of this study
      support the hypothesis that while a certain level of structural brain atrophy is
      necessary for delusion formation in patients with FES, excessive structural
      atrophy may in fact preclude the formation of highly systematized delusions.

PMID- 19395245
TI  - The influence of size, lipid composition and bilayer fluidity of cationic
      liposomes on the transfection efficiency of nanolipoplexes.
AB  - Among non-viral vectors, cationic liposomes are the most promising carriers in
      gene delivery. But the most critical issue about their application is their low
      transfection efficiency compared to viral vectors. In this study, we tried to
      make a comparison between transfection efficiency of different liposomal
      formulations and to investigate the effect of membrane fluidity and other
      physical properties of liposomes and lipoplexes such as size and charge ratio on
      the transfection efficiency in in vitro environment. Different gene delivery
      systems were developed by using liposomes composed of 1,2-dioleoyl-3
      trimethylammonium-propane (DOTAP) or 3-beta-[N-(N'N'-dimethylaminoethane)
      carbamoyl] cholesterol (DC-CHOL) in combination with other lipids including 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine (DOPE), egg L-alpha-phosphatidylcholine (EPC) and 1,2
      dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE). These multilamellar vesicle
      (MLV) liposomes were extruded through 100 nm polycarbonate filters to produce
      small unilamellar vesicles (SUVs). Transfection activity of these lipoplexes in
      Neuro2A cells was tested using pRL-CMV encoding Renilla luciferase. We could not
      establish any direct correlation between high fluid membranes and high
      transfection efficiency because DOTAP:DPPE had a better result than DOTAP:DOPE
      while DC-CHOL:DOPE was more successful in gene transfer than DC-CHOL:DPPE. It was
      revealed that the use of these two helper lipids with different Tm (DPPE: 64
      degrees C and DOPE: -11 degrees C) along with DOTAP increased transfection
      efficiency but formulation of these phospholipids with DC-CHOL was led to a
      significant reduction in transfection activity. Generally, DOTAP:DPPE, DC
      CHOL:DOPE and DOTAP:DOPE:DPPE formulations showed the highest transfection
      activity. The results of this study showed that, in designing of liposome based
      non-viral vectors, different parameters such as size, lipid composition and the
      use of helper lipid should be considered.

PMID- 19395246
TI  - Enhanced growth inhibition effect of resveratrol incorporated into biodegradable
      nanoparticles against glioma cells is mediated by the induction of intracellular
      reactive oxygen species levels.
AB  - Resveratrol (Res) has been reported to elicit many cellular responses including
      cell cycle arrest, differentiation, and apoptosis. This makes it a novel and
      potential anticancer agent. Moreover, the lipophilicity of Res raises the
      possibility of its application as a potential model drug in nanoparticle based
      delivery systems. Resveratrol is incorporated into mPEG-PCL based nanoparticles
      with high encapsulation efficiency due to its lipophilicity. The significant
      finding of the current study is that Res-loaded nanoparticles at lower
      concentration could lead to significantly higher cell death compared to
      equivalent dose of free Res and this difference of cytotoxicity could not be
      abrogated by the antioxidant Vitamin E. Furthermore, free Res shows significant
      less cytotoxicity than the equivalent dose of Res-loaded nanoparticles with the
      preconditioning of Vitamin E. Meanwhile, reactive oxygen species (ROS)
      determination revealed the significantly lower intracellular ROS levels in Res
      treated cells compared to nanoparticle-treated cells. Therefore, the differential
      cytotoxicity between Res and Res-loaded nanoparticles may be mediated by the
      discrepancy of intracellular ROS levels. The present results suggest that Res
      loaded nanoparticles could be a potential useful chemotherapeutic formulation for
      malignant glioma therapy and the development of traditional Chinese medicine with
      nanoscale drug formation warrants more intensive research in order to evaluate
      its clinical feasibility.

PMID- 19395247
TI  - Comparison of the physicochemical properties of MCT-containing fat emulsions in
      total nutrient admixtures.
AB  - The physical stability of two types of MCT-emulsions made by different
      technologies - physical mixture vs. structured lipids - was studied as a function
      of storage time and temperature. Particle size analysis, zeta potential and
      dynamic surface tension measurements were carried out to evaluate the possible
      changes in the kinetic stability of the emulsions. Our results indicate that the
      physical mixture technology of MCT-emulsions resulted in impaired physicochemical
      stability compared to the ones containing structured triglycerides. In the case
      of structured lipids, both medium and long chain fatty acids can be found in one
      triglyceride molecule, leading to a favorable interfacial location of structured
      triglycerides. Besides the advantageous metabolic effects of structured
      triglycerides, their application is recommended to improve the physical stability
      of TPN admixtures.

PMID- 19395248
TI  - Investigations on the correlation of advanced glycated end products (AGE)
      associated fluorescence with blood glucose and oxidative stress in ethanol
      administered diabetic rats.
AB  - Diabetes mellitus and alcoholism are two well-known agents causing pathological
      complications in the body. Both cause oxidative stress and derangements in
      glucose homeostasis. Advanced glycated end products (AGEs) are formed in
      hyperglycemia and can cause pathological changes. In this study, we investigated
      the relationship between AGE-associated fluorescence, in serum, tail tendon
      collagen, and eye lens with blood glucose and serum malondialdehyde (MDA) in
      alcohol administered diabetic rats. Blood glucose and glycated hemoglobin
      (HbA(1)C) decreased in ethanol-administered diabetic rats. Elevated AGE
      associated fluorescence in serum, eye lens and tail tendon collagen were observed
      in alcoholic diabetic rats in spite of the reduced blood glucose levels compared
      to other groups. AGE-associated fluorescence correlated positively with serum MDA
      than with blood glucose. Up-regulation of the nuclear translocation of NFkappaB
      was more profound in the ethanol-administered diabetic group indicating the
      development of pathological complications. This indicates that the toxicity
      induced by diabetes has been potentiated in alcohol administered diabetic rats.
      Our histopathological studies also reinforce our findings. Hence serum AGE-linked
      fluorescence has the potential to be developed as a surrogate biomarker for
      oxidative stress.

PMID- 19395249
TI  - HIV infection and risk behaviour of primary fentanyl and amphetamine injectors in
      Tallinn, Estonia: implications for intervention.
AB  - BACKGROUND: Following a heroin shortage, fentanyl and 3-methylfentanyl, known as
      "China White" and "White Persian", have become the most widely used drugs, along
      with amphetamine, among injecting drug users (IDUs) in Tallinn, Estonia. METHODS:
      In order to assess the relationships between the injection of fentanyl and
      amphetamine, and levels of HIV prevalence and risk behaviour, 350 current IDUs
      were recruited using respondent-driven sampling for an interviewer-administered
      unlinked cross-sectional survey and HIV testing. IDUs were categorised into
      groups based on self-report of the main drug used within the last 28 days.
      RESULTS: 77% (256/331) of participants reported fentanyl and 23% (75/331)
      amphetamine as their main drug of injection. HIV prevalence was 27% (95%
      confidence interval [CI]: 18.45-35.51) and 62% (95% CI: 56.97-67.03) among
      amphetamine and fentanyl injectors, respectively. After adjustment, fentanyl
      injectors had three times the odds of being HIV positive (adjusted odds ratio
      [AOR]=2.89; 95% CI: 1.55-5.39). They also had higher odds for injecting in the
      street with a previously used needle/syringe (AOR=2.39; 95% CI: 1.14-5.04) and
      sharing a needle/syringe with somebody known to have HIV (AOR=3.00, 95% CI: 1.33
      6.79). Fentanyl injectors also had higher odds for lifetime overdose (AOR=3.02,
      95% CI: 1.65-5.54). CONCLUSION: The injection of fentanyl is associated with
      elevated injecting risk behaviour derived from injection practice and situational
      risk factors, and needs urgently targeted interventions.

PMID- 19395250
TI  - A qualitative inquiry into methadone maintenance treatment for opioid-dependent
      prisoners in Tehran, Iran.
AB  - BACKGROUND: This study aimed to investigate the context in which methadone
      maintenance treatment (MMT) is provided for opioid-dependent prisoners, and to
      identify barriers against further scale-up of MMT in Ghezel Hesar prison in
      Tehran. METHODS: This was a cross-sectional qualitative study using field
      observations, focus group discussions, and individual interviews. In total, 30
      prisoners and 15 prison staff and health policymakers participated in this study
      in November 2006. RESULTS: The rate of drug injecting in the prison unit was
      unanimously reported to have decreased drastically since introducing the MMT
      program. In addition to the health benefits to MMT recipients, interview data
      indicates that MMT has had positive effects on socio-economic status of
      prisoners' families. Nevertheless, several impediments to the provision of MMT
      services and to its further expansion were also identified, including staff
      shortages, some degree of methadone diversion, widespread concerns over the
      possible side effects of methadone, and the stigma attached to methadone
      treatment. CONCLUSION: MMT constitutes one of the main components of the Iran
      Prison Organization's comprehensive HIV prevention package and is becoming
      increasingly accessible to opioid-dependent prisoners in Iran. Our findings
      indicate that the MMT program in Ghezel Hesar prison has been helpful for many
      opioid-dependent prisoners to reduce their risk of drug-related harm and to ease
      social and financial burden over their families. Meanwhile, existing barriers
      against provision of MMT should be properly addressed before further scale up of
      the program.

PMID- 19395251
TI  - The effect of shredding and test apparatus size on compressibility and strength
      parameters of degraded municipal solid waste.
AB  - In many situations, MSW components are processed and shredded before use in
      laboratory experiments using conventional soil testing apparatus. However,
      shredding MSW material may affect the target property to be measured. The
      objective of this study is to contribute to the understanding of the effect of
      shredding of MSW on the measured compressibility and strength properties. It is
      hypothesized that measured properties can be correlated to an R-value, the ratio
      of waste particle size to apparatus size. Results from oedometer tests, conducted
      on 63.5 mm, 100 mm, 200 mm diameter apparatus, indicated the dependency of the
      compressibility parameters on R-value. The compressibility parameters are similar
      for the same R-value even though the apparatus size varies. The results using
      same apparatus size with variable R-values indicated that shredding of MSW mainly
      affects initial compression. Creep and biological strain rate of the tested MSW
      are not significantly affected by R-value. The shear strength is affected by
      shredding as the light-weight reinforcing materials are shredded into smaller
      pieces during specimen preparation. For example, the measured friction angles are
      32 degrees and 27 degrees for maximum particle sizes of 50 mm and 25 mm,
      respectively. The larger MSW components in the specimen provide better
      reinforcing contribution. This conclusion is however dependent on comparing
      specimen at the same level of degradation since shear strength is also a function
      of extent of degradation.

PMID- 19395252
TI  - A simple strategy for one-step construction of bienzyme biosensor by in-situ
      formation of biocomposite film through electrodeposition.
AB  - One-step construction of horseradish peroxidase (HRP) and glucose oxidase (GOD)
      bienzyme biosensor was established based on a simple and controllable
      electrodeposition approach by in-situ formation of biocomposite film on
      electrode. With hydrogen peroxide (H(2)O(2)) instantly generated by GOD-catalyzed
      oxidation of glucose, quantitative measurement of glucose could be achieved. In
      the proposed electrodeposition strategy, Concanavalin A (Con A) was applied as
      bifunctional cross-linker for in-situ incorporating of HRP-GOD in biocompatible
      chitosan (CS) matrix due to its biospecific affinity interaction with CS and
      glycoproteins. Scanning electron microscopy showed that the HRP-GOD/Con A/CS
      biocomposite film possessed highly porous surface. The developed bienzyme
      biosensor exhibited a fast amperometric response for the determination of
      glucose. The linear response of the developed biosensor for the determination of
      glucose ranged from 1.0x10(-6) to 2.2x10(-4) M with a detection limit of 6.7x10(
      7) M. The biosensor can be used to determine glucose in serum directly. The
      biosensor presented high stability owing to the design of the introduction of Con
      A and instant generation of H(2)O(2) with bienzyme system. The one-step
      construction of biosensor based on non-manual technique in biocompatible
      environment was direct and facile.

PMID- 19395253
TI  - Assembling the presynaptic active zone.
AB  - Rapid neurotransmission depends on the structural and functional integrity of
      synaptic connections. How synapses assemble is currently being intensely
      investigated to help our understanding of neuronal development and synaptic
      plasticity. Here we focus on the assembly of the presynaptic active zone, which
      regulates the synaptic vesicle exo/endo-cycle and is characterized by
      ultrastructural specializations and large scaffold proteins. While genetic and
      biochemical studies from rodents, Caenorhabditis elegans and Drosophila have
      started to identify proteins organizing active zone assembly, drawing a coherent
      picture remains challenging, with genetically established hierarchies and protein
      protein interactions still to be placed into spatio-temporal and functional
      context. Recent advances in light and electron microscopy, together with in vivo
      imaging of protein traffic, will help to tackle this challenge.

PMID- 19395254
TI  - Optimising the biogas production from leather fleshing waste by co-digestion with
      MSW.
AB  - Waste from the leather industry, known as limed leather fleshing (LF), has a low
      C:N (3.2) and an alkaline pH of 11.4. This is a major disadvantage for anaerobic
      digestion due to ammonia toxicity for methanogenesis. This study describes co
      digestion of LF with biodegradable fraction of municipal solids waste optimised
      over a range of C:N and pH to minimise ammonia and to maximise biogas yield. The
      optimum conditions were found with a blend that provided C:N of 15 and pH of 6.5
      and the cumulative biogas yield increased from 560 mL using LF fraction alone, to
      6518 mL with optimum blend. At higher pH of 8.5, unionised ammonia was high (2473
      mg L(-1)) coincided with poor biogas yield (47 m Ld(-1)) that confirms ammonia
      toxicity. By contrast at a pH of 4.5 the ammonia was minimum (510 mg L(-1)), but
      high VFA (26,803 mg L(-1)) inhibited the methanogens. Biomass activity measured
      using ATP correlated well with biogas yield as reported previously.

PMID- 19395255
TI  - A novel reforming method for hydrogen production from biomass steam gasification.
AB  - In this work, an experimental study of biomass gasification in different
      operation conditions has been carried out in an updraft gasifier combined with a
      porous ceramic reformer. The effects of gasifier temperature, steam to biomass
      ratio (S/B), and reforming temperature on the gas characteristic parameters were
      investigated with and without porous ceramic filled in reformer. The results
      indicated that considerable synergistics effects were observed as the porous
      ceramic was filled in reformer leading to an increase in the hydrogen production.
      With the increasing gasifier temperature varying from 800 to 950 degrees C,
      hydrogen yield increased from 49.97 to 79.91 g H(2)/kg biomass. Steam/biomass
      ratio of 2.05 seemed to be optimal in all steam-gasification runs. The effect of
      reforming temperature for water-soluble tar produced in porous ceramic reforming
      was also investigated, and it was found that the conversion ratio of total
      organic carbon (TOC) contents is between 71.08% and 75.74%.

PMID- 19395256
TI  - Production and characterization of homopolymer poly(3-hydroxyvalerate) (PHV)
      accumulated by wild type and recombinant Aeromonas hydrophila strain 4AK4.
AB  - Aeromonas hydrophila 4AK4 normally produces copolyesters (PHBHHx) consisting of 3
      hydroxybutyrate (C4) and 3-hydroxyhexanoate (C6). Wild type and recombinant A.
      hydrophila 4AK4 (pSXW02) expressing vgb and fadD genes encoding Vitreoscilla
      haemoglobin and Escherichia coli acyl-CoA synthase respectively, were found able
      to produce homopolyester poly(3-hydroxyvalerate) (PHV) (C5) on undecanoic acid as
      a single carbon source. The recombinant grew to 5.59 g/L cell dry weight (CDW)
      containing 47.74 wt% PHV in shake flasks when growth was conducted in LB medium
      and PHV production in undecanoic acid. The cells grew to 47.12 g/L CDW containing
      60.08 wt% PHV in a 6 L fermentor study. Physical characterization of PHV produced
      by recombinant A. hydrophila 4AK4 (pSXW02) in fermentor showed a weight average
      molecular weight (M(w)) of 230,000 Da, a polydispersity of 3.52, a melting
      temperature of 103 degrees C and a glass transition temperature of -15.8 degrees
      C. The degradation temperature at 5% weight loss of the PHV was around 258
      degrees C.

PMID- 19395257
TI  - Bioaerosols associated with animal production operations.
AB  - Air emissions from animal housing and manure management operations include a
      complex mixture of biological, microbial, and inorganic particulates along with
      odorous volatile compounds. This report highlights the state of current issues,
      technical knowledge, and remaining challenges to be addressed in evaluating the
      impacts of airborne microorganisms, dusts, and odorants on animals and workers at
      animal production facilities and nearby communities. Reports documenting
      bioaerosol measurements illustrate some of the technical issues related to sample
      collection, analysis, as well as dispersion and transport to off-farm locations.
      Approaches to analysis, mitigation and modeling transport are discussed in the
      context of the risk reduction and management of airborne spread of bioaerosols
      from animal operations. The need for standardization and validation of bioaerosol
      collection and analytical techniques for indoor as well as outdoor animal
      agriculture settings is critical to evaluation of health effects from modern
      animal production systems that are increasingly situated near communities.

PMID- 19395258
TI  - Computer-aided rational molecular design of argifin-derivatives with increased
      inhibitory activity against chitinase B from Serratia marcescens.
AB  - Argifin, a novel pentapeptide chitinase inhibitor isolated from Gliocladium
      fungal culture, is a promising candidate for the development of new fungicides,
      insecticides, and anti-asthma medications. In this study, we undertook rational
      molecular design of argifin-derivatives and tested them against chitinase B from
      Serratia marcescens (SmChiB). The work involved molecular dynamics simulation
      with explicit water molecules, the molecular docking calculation, and free-energy
      analysis using the molecular mechanics Poisson-Boltzmann surface area method. The
      custom-designed derivatives were synthesized via effective solid phase synthesis,
      developed recently in our laboratory, and their inhibitory activities were
      measured against SmChiB. Finally, we identified and obtained a derivative which
      exhibited 28-fold more inhibition than argifin itself, a compound in which the d
      Ala(5) of argifin was replaced with d-Leu and the 4-benzylpiperdine was attached
      to l-Asp(4).

PMID- 19395259
TI  - Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2
      yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90
      inhibitors.
AB  - A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5
      dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones, have been designed
      and identified as potent and selective inhibitors of Hsp90. These compounds
      demonstrated nanomolar potency toward both Hsp90-regulated Her2 degradation and
      the growth of a panel of human tumor cell lines in cell-based assays. High
      selectivity of these compounds toward Hsp90 was evident given that they did not
      inhibit a panel of 34 kinases at 10microM. The structure-activity relationship
      (SAR) of this series is reported here.

PMID- 19395260
TI  - Discovery and structure-activity relationships of pentanedioic acid diamides as
      potent inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
AB  - Benzylamides of pentanedioic acid were identified as inhibitors of 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1) by high-throughput screening.
      Optimisation to 2-adamantyl amides yielded inhibitors with single digit nanomolar
      IC(50)s on the 11beta-HSD1 human isoform. The hydroxy adamantyl amide lead
      compound was selective against 11beta-hydroxysteroid dehydrogenase type 2
      (selectivity ratio >1000) and displayed good inhibition of 11beta-HSD1
      (IC(50)<0.1microM) in a cellular model (3T3L1 adipocytes).

PMID- 19395261
TI  - Microwave assisted synthesis of new indophenazine 1,3,5-trisubstruted pyrazoline
      derivatives of benzofuran and their antimicrobial activity.
AB  - 2-[1-(5,8-Dihydro quinoxalino[2,3-b]indoloacetyl)-3-(1-benzofuran-2-yl)-4,5
      dihydro-1H-pyrazol-5-yl] phenyl derivatives were synthesized from 2-(5,8-dihydro
      quinoxalino[2,3-b]indol-5-yl) acetohydrazide and (2E)-1-(1-benzofuran-2-yl)-4
      phenylbut-2-en-1-ones derivatives using microwave-assisted route. The structures
      of all the compounds have been established on the basis of analytical and
      spectral data. Among the 14 compounds IPB-1, IPB-5, IPB-10, IPB-11 and IPB-12
      were found good antibacterial activity and MICs were found bellow 10microg/mL
      against Escherichia coli, Pseudomonas aeruginosa and Streptococcus aureus, which
      can compared with sparfloxacin and norfloxacin.

PMID- 19395262
TI  - Cyclic glycopeptidomimetics through a versatile sugar-based scaffold.
AB  - Cyclic peptidomimetics are attracting structures to obtain a distinct, bioactive
      conformation. Even more attractive are sugar-containing cyclic peptidomimetics
      which present turn structures induced by the pyranose ring when incorporated in
      cyclic peptides. The use of a new and versatile saccharidic scaffold to achieve
      sugar-based peptidomimetics is here reported together with the successful
      synthesis of diastereomerically pure cyclic SAA peptidomimetics 15 and 16.

PMID- 19395263
TI  - Towards calixarene-based prodrugs: Drug release and antibacterial behaviour of a
      water-soluble nalidixic acid/calix[4]arene ester adduct.
AB  - A water-soluble calixarene-based heterocyclic podand incorporating a quinolone
      antibiotic subunit, the nalidixic acid, was synthesised and fully characterised.
      Its prodrug behaviour was assessed in vitro by HPLC, demonstrating the release of
      the tethered quinolone in model biological conditions. Microbiological studies
      performed on various Gram-positive and Gram-negative reference strains showed
      very interesting antibacterial activities.

PMID- 19395264
TI  - To have and to hold nutritional control: balancing between individual and routine
      care. A grounded theory study.
AB  - OBJECTIVES: Gaining insight into nutritional processes can help nurses and other
      staff in their work. The aim was to provide a theoretical understanding of the
      concerns and strategies of nutritional nursing care for patients with enteral
      nutrition in intensive care units. DESIGN: A grounded theory approach was used.
      Observations of patient's nutritional care and twelve interviews with eight
      registered nurses and four enrolled nurses were conducted. SETTING: The study was
      carried out in one intensive care unit at a medium sized hospital in Sweden.
      RESULTS: The substantive theory developed included the core category "To have and
      to hold nutritional control - balancing between individual care and routine
      care". The core category was reflected in and related to the categories "knowing
      the patient", "facilitating the patient's involvement", "being a nurse in a
      team", "having professional confidence" and "having a supportive organisation".
      Finding a balance between individual care and routine care was a way of enhancing
      the patient's well-being, security and quality of care. CONCLUSION: To have and
      to hold nutritional control over the patient's nutrition was found to be a
      balancing act between individual care and routine care. Organisation and teamwork
      are both challenging and supporting the provision, maintenance and development of
      nutritional care.

PMID- 19395265
TI  - Antiplasmodial and antitrypanosomal activity of bicyclic amides and esters of
      dialkylamino acids.
AB  - Several bicyclic amides and esters of dialkylamino acids were prepared. Their
      activities against a multiresistant strain of Plasmodium falciparum and against
      Trypanosoma brucei rhodesiense (STIB 900) were examined. Structure-activity
      relationships were discussed. Particularly the ester compounds showed good
      antiplasmodial and antitrypanosomal activity and a single compound was tested in
      vivo against Plasmodium berghei.

PMID- 19395266
TI  - High-precision measurement of the half-life of 147Sm.
AB  - The half-life of the long-lived isotope (147)Sm was determined by means of
      activity determination using liquid scintillation counting. The amount of
      samarium was determined by ICP-OES using a NIST reference standard. The isotopic
      ratio N((147)Sm)/N(Sm) of the samples was measured by means of ICP-HRMS. The half
      life was found to be 1.070(9)x10(11) y. The result is in good agreement with
      other evaluations and the relative standard uncertainty of 0.8% is lower than in
      any previous work.

PMID- 19395267
TI  - Thirteenth International Congress on Neutron Capture Therapy.

PMID- 19395269
TI  - Boron neutron capture therapy for recurrent oral cancer and metastasis of
      cervical lymph node.
AB  - We treated 6 patients with recurrent oral cancer and metastasis to the cervical
      lymph nodes after conventional treatments in 5 and non-conventional in 1 using
      BNCT, and herein report our results. The clinical response in our patients ranged
      from CR to PD. In 5 cases, spontaneous pain decreased immediately after BNCT.
      Three of the 6 are alive at the time of writing and we found that BNCT
      contributed to QOL improvement in all.

PMID- 19395268
TI  - Disposition of TF-PEG-Liposome-BSH in tumor-bearing mice.
AB  - BNCT requires high concentration and selective delivery of (10)B to the tumor
      cell. To improve the drug delivery in BNCT, we conducted a study by devising
      TPLB. We administrated three types of boron delivery systems: BSH, PLB and TPLB,
      to Oral SCC bearing mice. Results confirmed that (10)B concentration is higher in
      the TPLB group than in the BSH group and that TPLB is significantly effective as
      boron delivery system.

PMID- 19395270
TI  - An overview of structural features of DNA and RNA complexes with saffron
      compounds: Models and antioxidant activity.
AB  - Saffron is the red dried stigmas of Crocus sativus L. flowers and used both as a
      spice and as a drug in traditional medicine. Its numerous applications as an
      antioxidant and anticancer agent are due to its secondary metabolites and their
      derivatives (safranal, crocetin, dimethylcrocetin). In this work we are comparing
      the spectroscopic results and antioxidant activities of saffron components
      safranal, crocetin (CRT) and dimethylcrocetin (DMCRT) complexes with calf-thymus
      DNA (ctDNA) and transfer RNA (tRNA) in aqueous solution at physiological
      conditions Intercalative and external binding modes of saffron compounds to DNA
      and RNA were observed with overall binding constants of K(safranal)=1.24x10(3)M(
      1), K(CRT)=6.20x10(3)M(-1) and K(DMCRT)=1.85x10(5)M(-1), for DNA adducts and
      K(safranal)=6.80x10(3)M(-1), K(CRT)=1.40x10(4)M(-1) and K(DMCRT)=3.40x10(4)M(-1)
      for RNA complexes. A partial B- to A-DNA transition occurred at high ligand
      concentrations, while tRNA remained in A-conformation in saffron-RNA complexes.
      The antioxidant activity of CRT, DMCRT and safranal was also tested by the DPPH
      (2,2-diphenyl-1-picrylhydrazyl) antioxidant activity assay and their IC(50)
      values were compared to that of well known antioxidants such as Trolox and
      Butylated Hydroxy Toluene (BHT). The IC(50) values were 95+/-1microg/mL for
      safranal and 18+/-1microg/mL for crocetin. The inhibition of DMCRT reached a
      point of 38.8%, which corresponds to a concentration of 40microg/mL.

PMID- 19395271
TI  - Influence of prolonged bed-rest on spectral and temporal electromyographic motor
      control characteristics of the superficial lumbo-pelvic musculature.
AB  - Little is known about the motor control of the lumbo-pelvic musculature in
      microgravity and its simulation (bed-rest). Analysis of spectral and temporal
      electromyographic variables can provide information on motor control relevant for
      normal function. This study examined the effect of 56-days of bed-rest with 1
      year follow-up in 10 male subjects on the median frequency and the activation
      timing in surface electromyographic recordings from five superficial lumbo-pelvic
      muscles during a repetitive knee movement task. Trunk fat mass (from whole body
      composition measurements) and movement accuracy as possible explanatory factors
      were included. Increased median frequency was observed in the lumbar erector
      spinae starting late in bed-rest, but this was not seen in its synergist, the
      thoracic erector spinae (p<.0001). These changes persisted up to 1-year after bed
      rest and were independent of changes in body-composition or movement accuracy.
      Analysis suggested decreases of median frequency (p<.0001) in the abdominal and
      gluteal muscles to result from increased (p<.01) trunk fat levels during and
      after bed-rest. No changes in lumbo-pelvic muscle activation timing were seen.
      The results suggest that bed-rest particularly affects the shorter lumbar erector
      spinae and that the temporal sequencing of superficial lumbo-pelvic muscle
      activation is relatively robust.

PMID- 19395272
TI  - Persistent sciatic artery and successful uterine artery embolization: report of
      three cases.
AB  - The incidence of persistent sciatic artery (PSA) was evaluated in the setting of
      uterine artery embolization (UAE) for symptomatic uterine leiomyomata over a 3
      year period. PSA was present in 0.83% of patients or 0.69% of limbs undergoing
      UAE at a single institution. The authors present three cases of PSA in which
      successful treatment with UAE was performed. Interventionalists should have
      thorough anatomic knowledge of PSA, and this rare yet important anatomic variant
      should be included among the pertinent findings during UAE.

PMID- 19395273
TI  - Percutaneous treatment of idiopathic chylopericardium.
AB  - Chylopericardium is a rare disease that may result from a variety of causes, such
      as cardiac surgery, trauma, obstruction of the thoracic duct near its drainage
      into the subclavian vein, or have no identifiable underlying cause. The present
      report describes a case of idiopathic chylopericardium in which percutaneous
      transabdominal occlusion of the thoracic duct was performed as an alternative to
      surgical duct ligation. The procedure was successful, resulting in a decrease in
      pericardial fluid accumulation. However, it failed to cure the patient, as
      constrictive pericarditis developed 2 months later, requiring surgical
      pericardectomy. Whether this could have been avoided by early (percutaneous)
      pericardial fenestration is unknown.

PMID- 19395274
TI  - Systemic air embolism following CT-guided lung biopsy.

PMID- 19395275
TI  - Radiofrequency endovenous ClosureFAST versus laser ablation for the treatment of
      great saphenous reflux: a multicenter, single-blinded, randomized study (RECOVERY
      study).
AB  - PURPOSE: The present study was designed to address the hypothesis that
      radiofrequency (RF) thermal ablation, as represented by the ClosureFAST system,
      is associated with improved recovery and quality-of-life (QOL) parameters
      compared with 980-nm endovenous laser (EVL) thermal ablation of the great
      saphenous vein (GSV). MATERIALS AND METHODS: Eighty-seven veins in 69 patients
      were randomized to ClosureFAST or 980-nm EVL treatment of the GSV. The study was
      prospective, randomized, single-blinded, and carried out at five American sites
      and one European site. Primary endpoints (postoperative pain, ecchymosis,
      tenderness, and adverse procedural sequelae) and secondary endpoints (venous
      clinical severity scores and QOL issues) were measured at 48 hours, 1 week, 2
      weeks, and 1 month after treatment. RESULTS: All scores referable to pain,
      ecchymosis, and tenderness were statistically lower in the ClosureFAST group at
      48 hours, 1 week, and 2 weeks. Minor complications were more prevalent in the EVL
      group (P = .0210); there were no major complications. Venous clinical severity
      scores and QOL measures were statistically lower in the ClosureFAST group at 48
      hours, 1 week, and 2 weeks. CONCLUSIONS: RF thermal ablation was significantly
      superior to EVL as measured by a comprehensive array of postprocedural recovery
      and QOL parameters in a randomized prospective comparison between these two
      thermal ablation modalities for closure of the GSV.

PMID- 19395276
TI  - Estimating radiation doses to the skin from interventional radiology procedures
      for a patient population with cancer.
AB  - PURPOSE: To estimate the peak radiation skin doses for interventional radiology
      cases performed at a cancer center, identify procedure types likely to result in
      skin doses exceeding the American College of Radiology's 3 Gy follow-up level,
      and determine a kerma area product (P(KA)) for use in monitoring. MATERIALS AND
      METHODS: A single-center retrospective study was performed to estimate doses from
      consecutive procedures performed during 2006. Of 6,598 procedures, 3,925 (60%)
      had P(KA) recorded and were included. Forty-three procedure types are
      represented. RESULTS: The median estimated peak skin dose was 39 mGy (third
      quartile, 205 mGy). In 2.6% of the cases, the estimated skin dose exceeded 3 Gy.
      No procedures resulted in skin doses greater than 15 Gy, and 94% of the cases
      resulted in skin doses less than 1 Gy. Procedure types with instances of skin
      doses greater than 1 Gy included hepatic, portal, and other arterial
      embolizations; diagnostic arteriography; biliary drainages; stent placements and
      catheter exchanges; nephrostomy/nephroureterostomy; urinary catheter exchanges;
      inferior vena cava filters; foreign body retrieval; abscess drainage; catheter
      exchange; and fistulography. Hepatic embolizations, nonhepatic arterial
      embolizations, and biliary drain/stent procedures were most likely to result in
      skin doses greater than 1 Gy. Significant variations in skin dose were noted
      within the same procedure type. No patients were noted to have developed any
      sequelae from radiation. CONCLUSIONS: It is unlikely that typical cases in an
      oncologic interventional radiology practice would exceed the Joint Commission's
      "reviewable sentinel event" skin dose level of 15 Gy. A P(KA) trigger of 300 Gy
      cm(2) could be used in the authors' clinic to identify follow-up requirements.

PMID- 19395277
TI  - Incidence and management of percutaneous transluminal angioplasty-induced venous
      rupture in the "fistula first" era.
AB  - PURPOSE: Percutaneous transluminal angioplasty (PTA)-induced venous rupture is a
      common complication of hemodialysis access interventions. The authors sought to
      determine if venous rupture rates and management differed between grafts and
      fistulas, and in the fistula subset, between transposed and nontransposed
      fistulas. MATERIALS AND METHODS: Patients experiencing venous rupture during
      hemodialysis PTA over a 5-year period were identified. Of 1,985 hemodialysis
      interventions, 75 ruptures occurred in 69 patients (46 women) with a mean age of
      63 years (range, 31-88 y). Rupture rates, proportion of successful treatments,
      and treatment type and number (ie, balloon tamponade, stent, covered stent) were
      determined. RESULTS: Rupture was more common in fistulas overall (5.6%, 39 of
      693) compared with grafts (2.8%, 36 of 1,292; P = .002), in transposed (10.7%, 20
      of 187) compared with nontransposed fistulas (3.8%, 19 of 506; P = .001), and in
      transposed fistulas compared with grafts (P = .0001). There was no significant
      difference between nontransposed fistulas and grafts. Treatment success (ie,
      resolution of extravasation) was the same among groups: 69% (27 of 39) in
      fistulas overall, 70% (14 of 20) in transposed fistulas, 68% (13 of 19) in
      nontransposed fistulas, and 72% (26 of 36) in grafts. There was a greater need
      for stents in grafts (38.9%, 14 of 36) compared with fistulas (12.8%, five of 39;
      P = .003). CONCLUSIONS: PTA-induced rupture is more common in fistulas than
      grafts, and this effect seems nearly entirely driven by transposed fistulas.
      Although rupture treatment in fistulas of all types yielded similar success to
      grafts, and graft ruptures were more difficult to treat than fistula ruptures,
      the high rupture rates in transposed fistulas attest to the increased difficulty
      of treating this subset of fistulas.

PMID- 19395278
TI  - The effects of heavy long-term exercise on ventricular myocyte shortening and
      intracellular Ca2+ in streptozotocin-induced diabetic rat.
AB  - OBJECTIVE: This study investigated whether exercise training, initiated at the
      onset of diabetes, could preserve the contractile properties of ventricular
      myocytes. RESEARCH DESIGN AND METHODS: The effects of a heavy exercise training
      program on shortening and intracellular Ca(2+) in unloaded ventricular myocytes
      from streptozotocin (STZ)-induced diabetic rats were examined. Animals were
      divided into four groups: control sedentary (CS), diabetic sedentary (DS),
      control heavy exercise (CHE), and diabetic heavy exercise (DHE). Exercise
      protocol: 5x60 min/week, 18 m/min, 5% gradient. Exercise training began 1 week
      after STZ treatment and continued for 12-23 (mean 17.5) weeks. RESULTS: Diabetes
      induced prolongation of time-to-peak (TPK) shortening (124+/-2 ms in DS compared
      to 97+/-2 ms in CS rats), which was further increased by exercise (133+/-3 ms in
      DHE and 112+/-2 ms in CHE myocytes). Diabetes had no significant effects on time
      to-half (THALF) relaxation of shortening (61+/-2 ms in DS compared to 56+/-2 ms
      in CS myocytes). Exercise induced significant prolongation of THALF in control
      (66+/-3 ms) but not in diabetic (69+/-3 ms) myocytes. Diabetes, though not
      exercise, significantly prolonged TPK (76+/-3 ms in DS compared to 64+/-2 ms in
      CS) and THALF recovery (160+/-5 ms in DS compared to 118+/-4 ms in CS) of the
      Ca(2+) transient. Neither diabetes nor exercise had significant effects on the
      amplitude of myocyte shortening and the Ca(2+) transient. CONCLUSIONS: Heavy long
      term exercise alters the dynamics but not the amplitude of unloaded myocyte
      contraction in the STZ-induced diabetic rat.

PMID- 19395279
TI  - Toll-like receptor 4 and inducible nitric oxide synthase gene polymorphisms are
      associated with Type 2 diabetes.
AB  - BACKGROUND: The toll-like receptor 4 (TLR4) and inducible nitric oxide synthase
      are proteins from the innate immune system that, when activated, can induce
      insulin resistance. Polymorphisms in these genes, TLR4 and NOS2, respectively,
      could affect the immune response, as well as the prevalence of Type 2 diabetes
      (T2DM). OBJECTIVE: The aim of the present study was to investigate the
      contribution of four polymorphisms (two from TLR4 and two from NOS2) to
      susceptibility to T2DM in a southeast Brazilian population. DESIGN: A total of
      211 patients with T2DM and 200 unrelated controls were genotyped for the
      Asp299Gly and Thr399Ile polymorphisms of the TLR4 gene and for the insertion
      (I)/deletion (D) AAAT and (CCTTT)n polymorphisms of the NOS2 promoter gene.
      RESULTS: With regard to the NOS2 promoter region, the data showed that the I
      allele of the I/D AAAT polymorphism was more prevalent in the T2DM group and that
      the L/L genotype of the (CCTTT)n polymorphism was also more frequent in the same
      group. In contrast, the 299Gly allele and the 399Ile allele from the Asp299Gly
      and Thr399Ile TLR4 gene polymorphisms, respectively, were associated with
      protection of T2DM. It is believed that the persistence of these genetic
      variations in human populations may be indicative of a selective advantage in the
      face of different environmental pressures. CONCLUSIONS: Genetic variations in the
      NOS2 gene promoter and TLR4 coding sequence may lead to deleterious and
      protective effects, respectively, arising from altered function of the innate
      immune system in patients with T2DM.

PMID- 19395280
TI  - Consequences of delayed pump infusion line change in patients with type 1
      diabetes mellitus treated with continuous subcutaneous insulin infusion.
AB  - OBJECTIVE: To systematically investigate the effect of lack of adherence to the
      recommended change in insulin pump infusion line use beyond 48 h and determine
      whether the type of insulin made a difference. RESEARCH DESIGN AND METHODS: This
      was a double-blind, randomized, crossover trial with 20 patients with diabetes
      mellitus I using insulins aspart and lispro without a line change for up to 100
      h. Using retrospective continuous glucose monitoring, we analyzed the average
      glucose over the day. Changes in serum 1,5-anhydroglucitol, carboxymethyllysine,
      and free 15-F(2t) isoprostane were also studied. RESULTS: From Day 2 to Day 5 of
      the pump line use, the daily average glucose level increased from 122.7 to 163.9
      mg/dl (P<.05), fasting glucose from 120.3 to 154.5 mg/dl (P<.05), postprandial
      glucose from 114.6 to 172.1 mg/dl (P<.05), and the daily maximum glucose from
      207.7 to 242.8 dl (P<.05 for the trend). Time period that the glucose was >180
      mg/dl increased from 14.5% to 38.3% (P<.05). Loss of control occurred despite
      increase in total daily insulin dose from 48.5+/-11.8 to 55.3+/-17.9 U (P=.05).
      There was no difference in loss of control between insulin types, and biomarkers
      measured did not change significantly. CONCLUSIONS: The insulin pump infusion
      should be changed every 48 h in patients using continuous subcutaneous insulin
      infusion (CSII), to avoid loss of glycemic control. In the short-term, this loss
      of glycemic control has no impact on oxidative stress and glycation.

PMID- 19395281
TI  - Cellular basis of diabetic nephropathy: V. Endoglin expression levels and
      diabetic nephropathy risk in patients with Type 1 diabetes.
AB  - Endoglin is an accessory receptor molecule that, in association with transforming
      growth factor beta (TGF-beta) family receptors Types I and II, binds TGF-beta1,
      TGF-beta3, activin A, bone morphogenetic protein (BMP)-2 and BMP-7, regulating
      TGF-beta dependent cellular responses. Relevant to diabetic nephropathy,
      endoglin, expressed in vascular endothelial and smooth muscle cells, fibroblasts,
      and mesangial cells, negatively regulates extracellular matrix (ECM). The aim of
      this study was to evaluate endoglin expression in cultured skin fibroblasts from
      patients with Type 1 diabetes with and without diabetic nephropathy. Kidney and
      skin biopsies were performed in 125 Type 1 diabetic patients. The 20 with the
      fastest rate of mesangial expansion (estimated by electron microscopy) and
      proteinuria ("fast-track") and the 20 with the slowest rate and normoalbuminuria
      ("slow-track"), along with 20 controls were studied. Endoglin mRNA expression was
      assessed by microarray and quantitative real-time polymerase chain reaction (QRT
      PCR) and protein expression by Western blot. Age and sex distribution were
      similar among groups. Diabetes duration was similar (20+/-8 vs. 24+/-7 years),
      hemoglobin A1c lower (8.4+/-1.2% vs. 9.4+/-1.5%), and glomerular filtration rate
      higher (115+/-13 vs. 72+/-20 ml/min per 1.73 m2) in slow-track vs. fast-track
      patients. Microarray endoglin mRNA expression levels were higher in slow-track
      (1516.0+/-349.9) than fast-track (1211.0+/-274.9; P=.008) patients or controls
      (1223.1+/-422.9; P=.018). This was confirmed by QRT-PCR. Endoglin protein
      expression levels correlated with microarray (r=0.59; P=.044) and QRTPCR (r=0.61;
      P=.034) endoglin mRNA expression. These studies are compatible with the
      hypothesis that slow-track Type 1 diabetic patients, strongly protected from
      diabetic nephropathy, have distinct cellular behaviors that may be associated
      with reduced ECM production.

PMID- 19395282
TI  - Arthrodesis in a neuropathic elbow after posttubercular spine syrinx.

PMID- 19395283
TI  - In vivo assessment of scapulohumeral rhythm during unconstrained overhead
      reaching in asymptomatic subjects.
AB  - BACKGROUND: The contribution of scapulothoracic and glenohumeral motion to
      overall shoulder motion remains difficult to determine. We sought to determine
      the exact ratio between these two motion components in order to better understand
      overall shoulder kinematics in asymptomatic individuals in unconstrained
      reaching. MATERIALS AND METHODS: This study assessed shoulder motion using bone
      fixed sensors to quantify scapulohumeral motion during unconstrained raising and
      lowering of the arm. Electromagnetic tracking devices rigidly fixed to bone pins
      recorded active scapular and humeral motion. RESULTS: We found a significant
      difference in the ratio of glenohumeral elevation to scapular upward rotation
      during arm raising (2.3) and lowering (2.7). Each degree of glenohumeral
      elevation yielded scapular upward rotation of 0.43 degrees (raising) compared
      with downward rotation of 0.37 degrees (lowering), across the motion arc. Until
      125 degrees of glenohumeral elevation, the scapula internally rotated and then
      externally rotated with further elevation. Scapular upward rotation and posterior
      tilting progressively increased until maximal elevation. Scapulohumeral rhythm
      was greatest in the first increment of raising the arm and higher overall when
      lowering the arm. DISCUSSION: Understanding these data allows improved evaluation
      of potential motion abnormalities in patients with shoulder pathology and may
      improve treatment for restoration of normal shoulder motion.

PMID- 19395284
TI  - Analysis of Mel-18 expression in prostate cancer tissues and correlation with
      clinicopathologic features.
AB  - OBJECTIVE: Mel-18 is a member of the polycomb group (PcG) of proteins, which are
      chromatin regulatory factors that play an important role in development and
      oncogenesis. This study was designed to investigate the clinical and prognostic
      significance of Mel-18 in the patients with prostate cancer. PATIENTS AND
      METHODS: Immunostaining with Mel-18 specific antibodies was performed on paraffin
      sections from 202 patients. Correlations between Mel-18 and the Gleason grading
      system, clinical stage, serum prostate-specific antigen (PSA) levels, and age
      were evaluated. PSA recurrence in 76 patients who underwent radical prostatectomy
      and survival in 59 patients with metastases at diagnosis were analyzed to
      evaluate the influence of Mel-18 expression in cancer progression using Kaplan
      Meier analysis and multivariate Cox regression analysis. RESULTS: Staining was
      seen in all prostatic tissues. Mel-18 expression was significantly reduced in the
      prostate cancer patients with PSA levels over 100 ng/ml (P=0.009), advanced
      clinical stage (>T4, N1, or M1 disease, P=0.029), higher Gleason grade or with a
      higher Gleason score (P=0.018) than in those with other clinicopathologic
      features. Negative expression of Mel-18 was associated with significantly higher
      rates of PSA recurrence after radical prostatectomy than with positive expression
      of Mel-18 (P = 0.029), and was an independent predictor of PSA recurrence
      (P=0.034, HR=2.143) in multivariate analysis. Similarly, metastatic prostate
      cancer patients with negative expression of Mel-18 showed significantly worse
      survival compared with the positive expression of Mel-18 (P=0.025). In
      multivariate analysis, negative expression of Mel-18 was an independent predictor
      of cancer-specific survival (P=0.024, HR=2.365). CONCLUSION: Our study provides
      important evidence for the recognition of Mel-18 as a tumor suppressor. The
      expression of Mel-18 showed potential as a prognostic marker for human prostate
      cancer.

PMID- 19395285
TI  - Intravesical mitomycin C combined with hyperthermia for patients with T1G3
      transitional cell carcinoma of the bladder.
AB  - OBJECTIVES: Non-muscle invasive bladder cancer (NMIBC) classified as T1G3
      represents one of the most challenging issues in urologic oncology. Although it
      is still considered a lesion amenable for conservative management, the risk for
      recurrence and progression remains high. The aim of this study was to define both
      recurrence and progression rate in patients with T1G3 UCC treated by complete
      transurethral resection (TURT) and adjuvant thermochemotherapy approach.
      MATERIALS AND METHODS: We retrospectively evaluated the clinical data of patients
      with T1G3 NMIBC who underwent TURT followed by thermochemotherapy (TCT)
      treatment. Data recorded included age, gender, previous resections, previous
      intravesical treatment, time to tumor recurrence, and progression. TCT was given
      once weekly for 6 consecutive weeks, followed by 6 maintenance sessions at 4 to 6
      weeks intervals. During each treatment session, 40 mg of mitomycin C (MMC) was
      instilled into the bladder in combination with bladder wall hyperthermia of 42 +/
      2  degrees C for 60 minutes. Follow-up cystoscopy and urinary cytology were
      performed every 3 months for the first 2 years and than biannually. RESULTS: A
      total of 56 T1G3 patients were treated with adjuvant TCT treatment at 7 urologic
      centers. Mean age was 68 years (range 35-91), 10 were females and 46 were males.
      Twenty-six patients failed on at least 1 previous intravesical treatment. Five
      patients who dropped out due to adverse events before reaching the first outcome
      evaluation cystoscopy were referred to another intravesical therapy, and were
      therefore excluded from the current analysis. A total 51 patients were available
      for analysis. Median follow-up time of tumor-free patients was 18 months (average
      20, range 2-49 months). Seventeen patients (33.3%) had tumor recurrence and 4 of
      them progressed to muscle invasive disease. The median time to recurrence was 9
      months (average 11, range 2-31 months). The Kaplan-Meier estimated recurrence
      rate for this group is: 42.9% at 2 years, 51.0% at 4 years. CONCLUSIONS: TCT can
      be an effective adjuvant treatment option after TURT to prevent recurrence in
      patients with T1G3 NMIBC. Progression rate after this treatment was low (7.9%).
      TCT treatment was documented to be effective also in those who failed previous
      intravesical BCG. Treatment was confirmed to be safe and well tolerated.

PMID- 19395286
TI  - WAVE3 is associated with invasiveness in prostate cancer cells.
AB  - INTRODUCTION: Wiskott-Aldrich syndrome verprolin-homologous 3 (WAVE3) belongs to
      Wiskott-Aldrich syndrome family proteins (WASP), which, along with other members,
      play a critical role in the regulation of actin polymerization and cell motility.
      We investigated the expression pattern and the effects of manipulating endogenous
      WAVE3 expression in prostate cancer cells. MATERIALS AND METHODS: Reverse
      transcriptase-polymerase chain reaction (RT-PCR) of prostate cell lines and
      immunohistochemical staining of normal and cancer specimens for WAVE3 proteins
      were done. WAVE3 knockdown clones were synthesized using hammerhead ribozyme
      transgenes and transfected by electroporation into DU-145 and PC-3 cells. The
      impact of WAVE3 knockdown was studied using in vitro functional assays. RESULTS:
      RT-PCR for WAVE3 showed strong expression in both PC-3 and DU-145 cell lines.
      Immunohistochemistry of prostate tissue specimens showed that the cytoplasm of
      cancer cells had stronger staining than normal epithelium. The mean [(+/-standard
      error of mean (SEM)] invading cell number for PC-3(DeltaW3R1) and PC-3(DeltaW3R2)
      was 5.06 (+/-0.42) and 6.33 (+/-0.19), respectively, compared with PC-3(WT)
      (12.27 +/- 0.42; P < 0.001). Similarly, the mean (+/-SEM) invading cell numbers
      for DU-145(DeltaW3R1) and DU-145(DeltaW3R2) were 10.80 (+/-1.33) and 10.20 (+/
      0.86) compared with DU-145(WT) (14.80 +/- 0.24, P < 0.05). No significant
      differences were observed in the adhesiveness and proliferation between the
      knockdown mutants and the wild types. CONCLUSIONS: This is the first report on
      the expression patterns and the functions of WAVE3 in prostate cancer cell lines.
      This study shows that WAVE3 is pivotal in controlling the invasiveness of
      prostate cancer cells. Further work is needed to assess WAVE3 as a potential
      marker for predicting tumor aggressiveness.

PMID- 19395287
TI  - Impact of surgeon and hospital volume on outcomes of radical prostatectomy.
AB  - An emerging body of literature has established a relationship between case volume
      and outcomes after radical prostatectomy (RP). Such findings come in the context
      of an already well-established association between both surgeon and hospital case
      volume in the field of cardiovascular surgery and for several high-risk cancer
      operations. The purpose of this review is to identify and summarize the seminal
      studies to date that investigate the impact of RP volume on patient outcomes. We
      performed a literature search of the English language studies available through
      PubMed that pertain to this topic. Thirteen original studies and a meta-analysis
      were found, which focus on the impact of hospital RP volume on surgical outcomes
      (including length of stay, perioperative complication rate, perioperative
      mortality, readmission rate, and several long term measures of treatment effect).
      Eight studies were identified that interrogated the relationship between
      individual surgeon case volume and outcomes. Across multiple outcome metrics,
      there is a pervasive association between higher hospital RP case volume and
      improved outcomes. Increasing individual surgeon volume may also portend better
      outcomes, not only perioperatively, but even with respect to long-term cancer
      control and urinary function. While most data arise from retrospective cohort
      studies, these studies, for the most part, are of sound design, show an
      impressive magnitude of effect, and demonstrate an impact on outcome that is
      proportional to surgical volume. Further research should focus on finding a means
      by which to translate these observations into improvements in the quality of
      prostate cancer care. To address differences in outcome between low volume and
      high volume surgeons, some have proposed and implemented subspecialization within
      practice groups, while others have looked toward subspecialty certification for
      urologic oncologists. With regard to differences in hospital volume,
      regionalization of care has been proposed as a solution, but is fraught with
      pitfalls. It may be more pragmatic and, ultimately more beneficial to patients,
      however, to identify processes of care that are already in place at high volume
      hospitals and implement them at lower volume centers. Similarly, we advocate
      careful studies to identify successful surgical techniques of high volume
      surgeons and efforts to disseminate these techniques.

PMID- 19395288
TI  - The use of ultrasound to assist deployment of the StarClose vascular closure
      device in arterial access sites.
AB  - Access site complication rates remain relatively high following interventional
      procedures and have not been shown to be reduced by the use of vascular closure
      devices. This report describes an ultrasound-assisted technique of deploying one
      type of vascular closure device, the StarClose (Abbott Vascular, Illinois, USA).
      This technique has significantly reduced failure rates and complication rates
      since its introduction. The technique is relatively simple but requires
      familiarity with the use of ultrasound and the StarClose device.

PMID- 19395289
TI  - Endovascular stenting of a persistent sciatic artery aneurysm via retrograde
      popliteal approach: a durable option.
AB  - We report a case of acute lower limb ischaemia caused by a persistent sciatic
      artery aneurysm in a 55-year-old woman who was successfully managed by
      endovascular stenting via a retrograde popliteal approach. Four years following
      the procedure, she remains well, confirming the durability of the endovascular
      option.

PMID- 19395290
TI  - Durability of botulinum toxin treatment for axillary hyperhidrosis.
AB  - OBJECTIVES: Botulinum toxin injection effectively treats axillary hyperhidrosis.
      Durability estimates of 3-14 months, based on self re-referral may overestimate
      duration. Our objective was to determine treatment durability by active follow-up
      of patients. DESIGN: Audit of current practice. MATERIALS AND METHODS: Patients
      presenting with severe primary axillary hyperhidrosis were actively followed up
      for 24 months after intradermal injections of Botulinum Toxin A (Dysport 120
      units/axilla). A 10-point Likert Scale (1=worst imaginable symptoms, 10=absolute
      resolution) and the Hyperhidrosis Disease Severity Score (HDSS) were used at 1
      day and 3, 6, 12 and 24 months. We offered re-treatment when symptoms returned to
      the pre-intervention state. RESULTS: We treated 45 patients with a mean age of 29
      (15-49) years of whom 36 (78%) were women. The median pre-treatment Likert score
      (i.q.r.) of 3 (2-3) improved to 10 (10-10) on day 1. Scores at 3 (n=44), 6 (n=43)
      and 12 (n=39) months were 10 (10-10), 8 (7.5-10), and 7 (5-8) respectively. The
      median 24-month score was 3 (3-6) for 35 patients, including 11 patients with
      scores >/=6 who have not required re-treatment. HDSS scores followed a similar
      pattern. CONCLUSIONS: Axillary botulinum toxin treatment is durable. Patients
      experience gradual return of symptoms between 6 and 24 months. A minority do not
      require re-treatment at this time.

PMID- 19395291
TI  - Relationship of inferior oblique overaction to muscle bulk and position.
AB  - INTRODUCTION: The possible association between inferior oblique muscle overaction
      and inferior oblique muscle mass has been a matter of speculation. This study was
      performed to evaluate the anatomical position of the inferior oblique muscle and
      to determine any association between muscle mass and inferior oblique muscle
      overaction. METHODS: In this observational case series, eyes undergoing primary
      surgery for inferior oblique overaction underwent measurement of inferior oblique
      muscle borders distance from the limbus and muscle belly circumference. RESULTS:
      Overall, 78 eyes of 51 patients with mean age of 18.3 +/- 12.3 years (range, 1
      48) were evaluated. The mean distance of the anterior margin of the inferior
      oblique muscle from the limbus was 16.3 mm +/- 1.8 mm. The distance for the
      posterior margin was 20.8 mm +/- 1.9 mm. Average muscle circumference was 10.7 mm
      +/- 0.9 mm (range, 9 to 13). Inferior oblique muscle overaction and muscle belly
      circumference were not significantly correlated (p = 0.8). CONCLUSION: There was
      no detectable correlation of inferior oblique overaction with either muscle
      position or circumference.

PMID- 19395292
TI  - Parameters predicting outcomes of strabismus surgery in the management of Graves'
      ophthalmopathy.
AB  - BACKGROUND: Ocular dysmotility is a common feature of Graves' ophthalmopathy and
      frequently requires strabismus surgery. We reviewed the short-term results of
      strabismus surgery for Graves' ophthalmopathy to determine pre- and perioperative
      parameters predictive of postoperative outcome. METHODS: A retrospective review
      of Graves' ophthalmopathy patients who underwent strabismus surgery. Outcomes
      were correlated with preoperative and operative characteristics. The main outcome
      measure was field of binocular single vision score. Residual postoperative
      strabismus was considered a secondary outcome. Preoperative characteristics
      examined included age and laterality at onset, sex, disease activity, smoking
      status, and treatment for Graves' ophthalmopathy. Good outcome was defined as
      field of binocular single vision >50% and heterophoria in the primary position.
      Moderate outcome was defined as a field of binocular single vision 1% to 50% with
      heterotropia but with correctable diplopia in the primary position using prisms
      or head tilt. Poor outcome was defined as no measurable field of binocular single
      vision and intractable diplopia. RESULTS: Fifty patients were identified: 28
      women, 22 men; mean age, 54 years (SD +/- 12.8). Thirty-seven (74%) had good and
      13 (26%) had moderate or poor outcomes. Preoperative characteristics that were
      associated with good outcomes were symmetry of orbitopathy at Graves'
      ophthalmopathy onset (chi(2) = 7.5, p = 0.001) and earlier timing of surgery (t =
      -2.9, p = 0.003). CONCLUSION: Relative symmetry of orbitopathy at onset and a
      shorter time interval between onset of orbitopathy and surgery, while allowing
      for disease stability, are predictive of a good outcome following strabismus
      surgery for Graves' ophthalmopathy.

PMID- 19395293
TI  - Decompensating esophoria as the presenting feature of myasthenia gravis.
AB  - Myasthenia gravis is a disease in which antibodies directed at nicotinic
      acetylcholine receptors are produced, leading to a deficiency of acetylcholine
      receptors at the neuromuscular junction. This results in impairment of muscular
      excitation, which appears clinically as fatigable muscle weakness. Weakness of
      the extraocular muscles occurs in nearly 90% of all myasthenics at disease onset,
      with ptosis being the most common presenting feature. Myasthenia gravis affecting
      one or a combination of the extraocular muscles without ptosis is less common;
      however, cases such as bilateral internuclear ophthalmoplegia without ptosis have
      been described in the literature. The authors present a case in which
      decompensating esophoria was the presenting feature of myasthenia gravis.

PMID- 19395294
TI  - Isocaloric high-protein diet as well as branched-chain amino acids supplemented
      diet partially alleviates adverse consequences of maternal undernutrition on
      fetal growth.
AB  - Maternal undernutrition causes fetal growth restriction. Protein is a vital
      dietary nutrient for fetal growth, and branched-chain amino acids (BCAA) are
      noted to have anabolic actions. In this study, we investigated the effects of
      maternal high-protein diet or BCAA-supplemented diet upon fetal growth under the
      condition of maternal calorie restriction. Pregnant mice were calorie-restricted
      (undernutrition: UN), using either a standard diet (S-UN group), high-protein
      diet (HP-UN group), or BCAA-supplemented diet (BCAA-UN group) to 70% of the
      control; dams fed ad libitum with a standard diet (S-NN group) from 10.5days post
      coitum (dpc) to 18.5dpc. The fetal weights of UN groups were significantly
      decreased compared to that of S-NN. However, the fetal weights of HP-UN and BCAA
      UN were significantly higher by 5% and 4%, respectively, than those of S-UN,
      concomitant with augmentation of the gene and protein expressions of IGF-I and
      IGF-II in fetal liver. A high-protein diet as well as BCAA-supplemented diet
      partially improved fetal growth restriction caused by maternal calorie
      restriction, suggesting a pivotal role of them in the amelioration of fetal
      growth restriction.

PMID- 19395295
TI  - [Clinical trial of radial artery compression guided by mean arterial pressure].
AB  - OBJECTIVE: To determine whether a compression procedure guided by the patient's
      mean arterial pressure value (experimental) is safe and effective and superior to
      a compression procedure using 15 cubic centimeters of air in the device
      (standard) in patients undergoing radial artery catheterization. METHODS: We
      performed a randomized, single-center study, which included patients undergoing
      catheterization of the radial artery for diagnosis or percutaneous coronary
      intervention, in whom the sheath was removed at the end of procedure and the
      radial artery was compressed for 3 h with a pneumatic device (TR Band Terumo).
      The arteries were evaluated between 24 and 72 h after the procedure, using a
      plethysmography curve with a reverse flow test followed by bidirectional Doppler.
      RESULTS: The percentage of arterial occlusion was measured in 351 patients.
      Arterial occlusion was found in two patients (1.1%) in the experimental group
      compared with 21 patients (12%) in the standard group (p = 0.0001). No
      differences were found in the number of complications. CONCLUSIONS: The
      compression method, guided by the patient's mean arterial pressure value at the
      end of catheterization of the radial artery, is safe and effective and reduces
      arterial occlusion compared with the standard compression method using a
      pneumatic device.

PMID- 19395296
TI  - [The speciality of family and community nursing].

PMID- 19395297
TI  - [National research evaluation and financing agencies].

PMID- 19395298
TI  - Impact of prolonged treatment with linezolid on the human gut flora.
AB  - A 79-year-old male was treated for 6 months with linezolid for prosthetic knee
      joint osteomyelitis. At the end of this 6-month period, quantitative stool
      cultures revealed partial loss of the normal gut flora and concomitant
      colonization by opportunistic pathogens such as Pseudomonas aeruginosa and other
      Gram-negatives. Follow-up cultures at 6 weeks after antibiotic discontinuation
      revealed restoration of the normal flora. Prolonged linezolid administration may
      lead to replacement of normal gut flora by pathogenic microorganisms, which under
      certain conditions might cause systemic infections.

PMID- 19395299
TI  - Cardiac tamponade caused by polymicrobial gram-negative organisms.
AB  - Polymicrobial gram-negative pericarditis is a rare entity. We describe the first
      case of suppurative pericarditis with Citrobacter diversus and Proteus mirabilis.

PMID- 19395300
TI  - Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus
      outbreak among healthcare workers in a long-term care facility.
AB  - BACKGROUND: We investigated an outbreak of community-acquired methicillin
      resistant Staphylococcus aureus (MRSA) infections that occurred among healthcare
      workers (HCWs) but not among residents of a long-term care facility (LTCF).
      METHODS: Cases of S. aureus infection were sought by reviewing the medical
      records of residents and HCWs. In order to identify risk factors for the
      development of an S. aureus infection, an unmatched case-control study was
      conducted. Cases were all HCWs with a clinically compatible S. aureus infection;
      controls were HCWs with no history of a clinically compatible S. aureus
      infection. Cases and controls were interviewed and anterior nasal swabs were
      collected. RESULTS: Over a period of 14 months, a total of eight cases were
      identified among practice nurses, giving an attack rate of 10% for this category
      of profession. All isolates were identified as MRSA Panton-Valentine leukocidin
      (PVL)-producing SCCmec type IV. By multivariate analysis, working in a specific
      zone and being a practice nurse were found to be statistically significant risk
      factors for infection. CONCLUSIONS: The current outbreak indicates that HCWs may
      serve as vehicles for the entry of PVL-positive MRSA strains from the community
      into LTCFs, and that deficient hygiene practices and unrecognized carriage may
      facilitate spread. Given the increasing prevalence of PVL-positive MRSA
      infections worldwide, guidelines for the eradication of PVL-positive MRSA
      carriage within closed communities should be established and efforts to obtain
      cultures from compatible infections should be made.

PMID- 19395301
TI  - [Response of V. Lavoue to the article of G Akerman et al. Simplified technique of
      radioguided occult lesion localization in breast cancer: techniques of the
      future? Gynecol Obstet Fertil 2009;37:45-9].

PMID- 19395302
TI  - [Pregnancy following anonymous oocyte donation: Experience and feelings].
AB  - OBJECTIVES: This qualitative study focuses on feelings of women who receive an
      anonymous oocyte donation. PATIENTS AND METHODS: A heterogeneous group of 12
      women who were mothers or pregnant following a oocyte donation or who were
      waiting for a donation took part in the study. All women participated in a face
      to face or a telephone semi-directive interview. Questions dealt with desire for
      children, feelings about difficulties to have a child, place of the oocyte donor
      and position about revelation of origins. RESULTS: Several key ideas about the
      experience of oocyte donation can be brought out from the analysis of those
      interviews, particularly the psychological process implied in losing one's hope
      for a biological child, ambivalence towards donors, and questionings about this
      specific mode of conception. DISCUSSION AND CONCLUSION: Women's satisfaction when
      the project for having a child is brought to its completion, hides neither
      complexity nor psychological questionings entailed by the donation process which
      includes a third during the conception. This study underlines the need for
      psychological accompaniment.

PMID- 19395303
TI  - Biomechanical study of mandible bone supporting a four-implant retained bridge:
      finite element analysis of the influence of bone anisotropy and foodstuff
      position.
AB  - PURPOSE: The aim of this work was to study the biomechanical behavior of a "All
      on-four" implant-supported prosthesis through a finite element analysis using
      either isotropic or anisotropic properties of bone. The influence of foodstuff
      position during mastication was also analysed. MATERIALS AND METHODS: A three
      dimensional finite element model of a mandible with a prosthesis supported by
      four implants was developed. The geometry of the edentulous mandible and
      prosthesis was generated from computed tomography. Four MKIII implants (two
      vertical and two tilted) were modeled. The bone elastic properties used in the
      anisotropic simulations were orthotropic. The comparison of isotropic and
      anisotropic models was carried out in the loading condition of mastication with a
      foodstuff positioned on molar. Three distinct configurations, corresponding to
      three foodstuff positions, were then studied. MSC/Marc code was used to perform
      all computations. RESULTS: Significant differences in stress, strain, and strain
      energy densities were found in the comparison of isotropic and orthotropic
      models. Molar position was revealed to be the most critical one, from a stress
      and strain level point of view, for implants and framework and consequently for
      peri-implant bone. It was also observed that implant tilting leads to high stress
      concentrations in bone for the "All-on-four" concept. CONCLUSION: This study
      showed that the anisotropic behaviour of bone cannot be neglected in the
      numerical simulations. The actual design of the prosthesis is not optimal
      concerning the capacity of all metallic parts to support loads. Finally, it was
      demonstrated that the tilting of implants induced a high stress level at bone
      implant interface.

PMID- 19395304
TI  - Retrospective review of adverse incidents involving passengers seated in wheeled
      mobility devices while traveling in large accessible transit vehicles.
AB  - OBJECTIVE: Characterize wheeled mobility device (WhMD) adverse incidents on large
      accessible transit vehicles (LATVs) based on vehicle motion, WhMD activity during
      incident, incident scenario and injury. DESIGN: Retrospective records review.
      SUBJECTS/PATIENTS: WhMD passengers traveling on LATVs while remaining seated in
      their. METHODS: Adverse incidents characterized based on vehicle motion, WhMD
      activity during incident, and incident scenario. Injury characterized based on
      outcome, medical attention sought, vehicle activity, WhMD activity and incident
      scenario. RESULTS: 115 WhMD-related incident reports for years 2000-2005 were
      analyzed. Most incidents occurred when the LATV was stopped (73.9%), during
      ingress/egress (42.6%), and at the securement station (33.9%) when the LATV was
      moving. The combination of WhMD tipping and passenger falling (43.4%) occurred
      most frequently, and was 1.8 times more likely to occur during ingress/egress
      than at the securement station. One-third (33.6%) of all incidents resulted in
      injury, and injuries were equally distributed between ingress/egress (43.6%) and
      at the securement station (43.6%). CONCLUSIONS: WhMD users have a greater chance
      of incurring injury during ingress/egress than during transit. Research is needed
      to objectively assess real world transportation experiences of WhMD passengers,
      and to assess the adequacy of existing federal legislation/guidelines for
      accessible ramps used in public transportation.

PMID- 19395306
TI  - Spectroscopic study of fluorescent naphthoylenebenzimidazole derivatives in
      Langmuir-Blodgett films: self-aggregates formation.
AB  - Some derivatives of naphthoylenebenzimidazole as well as their mixtures with
      arachidic acid have been incorporated in Langmuir and Langmuir-Blodgett films.
      Surface pressure versus mean molecular area isotherms for Langmuir films were
      recorded and the organization of molecules at the air-water interface has been
      estimated. Absorption spectra in situ for Langmuir films and both absorption and
      fluorescence spectra for LB films have been recorded. The results obtained from
      spectroscopic studies have led to conclusions about formation of self-aggregates
      by dye molecules at interfaces. In the ground electronic state some fraction of
      the I- and J-type aggregates have been created, whereas in the excited state the
      creation of genuine excimers has been observed.

PMID- 19395307
TI  - Assessing the value of electronic prescribing in ambulatory care: a focus group
      study.
AB  - INTRODUCTION: Drug allergy and interaction alerts are a core function of most
      electronic prescribing (e-prescribing) systems. To characterize the value of e
      prescribing and medication safety alerts, especially in small and medium-size
      practices, we undertook a hypothesis-generating focus group study of
      Massachusetts clinicians. We sought to understand the reasons for adoption and
      use of e-prescribing, as well as clinicians' complaints about and perceived
      benefits of drug allergy and interaction alerts. METHODS: We recruited 25
      Massachusetts clinicians to participate in three focus groups regarding the use
      and value of e-prescribing and medication safety alerts. The participants
      included high-volume (>100 electronic scripts per month) physicians, nurse
      practitioners, and practice assistants in family practice, internal medicine,
      pediatrics, and subspecialty practices who used a common commercial e-prescribing
      system. RESULTS: Most clinicians were in small and medium-size group practices.
      Participants were, on average, 25 years post-medical school graduation (range 8
      36), had used e-prescribing for 2.5 years (range 1.0-5.5), and wrote the majority
      (89%, range 15-100%) of prescriptions electronically. The participants' decision
      to adopt e-prescribing was driven largely by financial incentives offered by
      insurers, and was viewed as a step toward implementation of an electronic medical
      record. Although participants agreed that the system was easy to learn, few
      anticipated efficiencies were realized until clinicians configured the device to
      meet their needs. The participants were ambivalent about whether e-prescribing
      improved their own or overall office efficiency, and--in the absence of payer
      incentives--few were willing to pay for the systems out-of-pocket. The most
      valuable aspects of e-prescribing were the ease of changing doses, renewing
      prescriptions, ensuring legibility, and transmitting prescriptions to in- and out
      of-state pharmacies. Participants were dissatisfied with the unreliability of
      transmitting prescriptions successfully to the pharmacy, and with their inability
      to merge duplicate patient entries, to create a comprehensive, allprescriber
      medication list, to write prescriptions for commonly ordered medications and
      supplies, and to enter allergy information into the system. Participants were
      critical of the volume of drug allergy and interaction alerts. Many alerts were
      of trivial clinical significance or were generated by interactions with out-of
      date medications. As a result, many clinicians habitually ignored these alerts.
      Alerts were most helpful to clinicians who were unfamiliar with a particular drug
      or patient. Although alerts rarely led the clinicians to abort or alter a
      prescription, alerts did prompt clinicians to counsel patients about medication
      side effects, to educate themselves about potential interactions, to check
      physical examination findings, or to order laboratory tests. Despite problems,
      few clinicians were willing to forego receiving alerts for fear that they would
      miss a potentially dangerous drug interaction. CONCLUSION: Electronic prescribing
      is a potential boon to ambulatory medical practice, although its value may be
      compromised by inappropriate and irrelevant medication safety alerts and by
      features of the e-prescribing system that prove burdensome to frontline
      clinicians. While alerts infrequently result in changed or aborted prescriptions,
      they may trigger a variety of other provider behaviors that help to ensure safe
      care.

PMID- 19395305
TI  - Synergistic combinations of signaling pathway inhibitors: mechanisms for improved
      cancer therapy.
AB  - Cancer cells contain multiple signal transduction pathways whose activities are
      frequently elevated due to their transformation, and that are often activated
      following exposure to established cytotoxic therapies including ionizing
      radiation and chemical DNA damaging agents. Many pathways activated in response
      to transformation or toxic stresses promote cell growth and invasion and
      counteract the processes of cell death. As a result of these findings many drugs,
      predominantly protein and lipid kinase inhibitors, of varying specificities, have
      been developed to block signaling by cell survival pathways in the hope of
      killing tumor cells and sensitizing them to toxic therapies. Unfortunately, due
      to the plasticity of signaling processes within a tumor cell, inhibition of any
      one growth factor receptor or signaling pathway frequently has only modest long
      term effects on cancer cell viability, tumor growth, and patient survival. As a
      result of this realization, a greater emphasis has begun to be placed on rational
      combinations of drugs that simultaneously inhibit multiple inter-linked signal
      transduction/survival pathways. This, it is hoped, will limit the ability of
      tumor cells to adapt and survive because the activity within multiple parallel
      survival signaling pathways has been reduced. This review will discuss some of
      the approaches that have been taken to combine signal transduction modulatory
      agents to achieve enhanced tumor cell killing.

PMID- 19395308
TI  - Evidence of circulation of Laguna Negra-like hantavirus in the Central West of
      Brazil: case report.
AB  - BACKGROUND: Hantavirus pulmonary syndrome has been reported with increasing
      frequency in some Brazilian regions, but information about viral genetic
      identification is still limited. Recently, the state of Mato Grosso, in the Legal
      Amazon of Brazil, experienced a growing number of hantavirus pulmonary syndrome
      (HPS) cases but the genetic characterization of the causative hantavirus is still
      missing. OBJECTIVES: Our goal was to identify the hantavirus strain involved in a
      fatal HPS case in the Central region of Brazil. STUDY DESIGN: Nested RT-PCR was
      conducted on blood clot samples from an HPS patient from Mato Grosso. PCR
      positive samples were sequenced, and the resulting sequences were compared with
      reference samples. Viral antigens were detected by immunohistological analyses in
      lung and liver tissues. RESULTS: Analyses of the viral RNA isolated from the
      patient identified a Laguna Negra (LN)-like virus as the causative agent and
      histological analysis of lung sections were compatible with the genetic
      characterization. CONCLUSIONS: This is the first report of circulation and human
      infection by a Laguna Negra-like hantavirus in Brazil.

PMID- 19395309
TI  - Detection and toxicity assessment of nitrosamines migration from latex gloves in
      the Chinese market.
AB  - Nitrosamines are potent carcinogens and have been found in latex products. In
      2007, twenty-seven natural latex gloves including sterile gloves, examination
      gloves and household use gloves were sampled from the Chinese market. This study
      monitored the migration of nitrosamines and nitrosatable substance from these
      gloves, and evaluated their mutagenicity using a Salmonella typhimurium mutation
      assay (Ames assay) with the strains TA98, TA97, TA100 and TA102 and by a
      micronucleus test (MN test) using ICR mice. In addition, the cytotoxicity of
      these compounds was determined by a MTT assay. N-nitrosodimethylamine (NDMA), N
      nitrosodiethylamine (NDEA) and N-nitrosodibutylamine (NDBA) were all found in
      samples treated with artificial sweat for 4h at 37 degrees C, and total
      nitrosamines varied from 18.89 to 244.51microg/Kg. The nitrosamine mixture of
      NDMA, NDEA and NDBA was used in both the Ames assay and the MN test. The
      proportion of NDMA, NDEA and NDBA (1:10:20) was selected according to the
      proportion of nitrosamines migration from sample E05. In the Ames assay, the
      lowest dose (1.98 x 10(-3)microg per plate) produced a positive result in the
      TA98 strain, corresponding to nitrosamines migration from sample E05 of 0.016g
      (the total nitrosamines migration from glove E05 was 122.55 microg/kg). The TA100
      strain responded positively at a dose of 4.96 x 10(-2)microg per plate,
      corresponding to nitrosamines migration from glove E05 of 0.040g. The MN test
      showed nitrosamine migration of 3.04 mg from 2066 pairs of sample E05 and could
      induce micronuclei in one mouse weighing 28g (average weight of one E05 glove was
      6g). Extracts from gloves were found to be cytotoxic and there was a significant
      correlation between cytotoxicity (IC50) and the release level of nitrosamines. In
      conclusion, in view of the high content of nitrosamines in latex gloves and the
      potential toxicity of nitrosamines migration from these gloves, it is suggested
      that both an effective and feasible detection method and prescribed limits should
      be imposed.

PMID- 19395310
TI  - Standardization of whole blood assay for determination of pyrogenic activity in
      organic dust samples.
AB  - To characterize bioaerosol exposure at workplaces standardized methods are
      necessary. Activity of endotoxin, one component of organic dust, can be
      quantified with the Limulus-Amoebocyte Lysat test (LAL test). Further information
      with respect to pyrogenic activity of the organic dust can be achieved by
      measuring cytokine release of human blood after stimulation with the dust or its
      extract (whole blood assay). The aim of our study was the standardization of the
      whole blood assay (WBA) while using cryo-preserved human blood (Qualis
      Laboratorium) and to compare the outcome of the different cytokines determined by
      incubation of the blood cells with extracts from dust samples collected at
      various workplaces. Cytokine release (IL-1 beta, IL-6, IL-8, TNF-alpha, MCP-1)
      was measured by ELISA after stimulation of fresh blood from ten donors as well as
      cryo-preserved human blood. In both cases blood was stimulated with E. coli
      endotoxin as well as with 30 dust filter extracts from various workplaces. All
      dust filter extracts were investigated in the WBA using cryo-preserved blood as
      well as with LAL test. E. coli endotoxin stimulated the release of IL-1 beta, IL
      6, IL-8, TNF-alpha and MCP-1 in a dose-dependent manner in fresh as well as cryo
      preserved human whole blood. 200 pg/ml E. coli endotoxin induced maximal cytokine
      release in cryo-preserved blood (mean value for IL-1 beta 2509+/-418 pg/ml; n=13
      experiments) whereas fresh blood of single donors reached a maximum release when
      stimulated with 50 ng/ml endotoxin (mean value of ten donors 1125+/-553 pg/ml IL
      1beta). Using cryo-preserved blood the coefficient of variation (CV) regarding
      the interassay variability was below 21% for all cytokines measured. Regarding 26
      dust sample extracts correlation coefficient r2 for LAL test and WBA was between
      0.90 and 0.93 (Pearson) for IL-1 beta, IL-6, IL-8 and TNF-alpha whereas
      correlation for MCP-1 was lower (r(2)=0.59). Two dust sample extracts which
      showed similar reactivity patterns in LAL test as well as in WBA with respect to
      IL-1 beta, IL-6, IL-8 and TNF-alpha could be differentiated by measuring MCP-1.
      In conclusion, cryo-preserved blood pools are suitable to standardize WBA.
      Combination of different outcome variables like IL-1 beta and MCP-1 improve the
      characterization from the inflammatory potency of workplace related dust samples.

PMID- 19395312
TI  - Quality of life and complementary and alternative medicine use among cancer
      patients in Turkey.
AB  - AIM: The purpose of this study was to assess the relationships between quality of
      life and use of complementary and alternative medicine (CAM) among Turkish cancer
      patients. METHODS: This cross-sectional study was conducted in Istanbul
      University Institute of Oncology, Turkey. Two-hundred patients were invited and
      informed consent was obtained, however 179 cancer patients completed the study.
      The Patient Characteristics form, The Nightingale Symptom Assessment Scale and
      The Functional Assessment of Cancer Therapy Scale were used in the evaluation of
      the patients' characteristics and quality of life. RESULTS: Some form of CAM had
      been used by 71.5% of the sample. Frequently used CAM methods appeared to be
      religious practices (68.2%) and only 37.4% of the patients used herbs. However,
      female patients, single patients, and individuals with metastatic disease and
      worse quality of life showed a tendency to use CAM more often. More than one
      third of our patients began to use CAM immediately after being diagnosed with
      cancer and factors associated with CAM use varied according to the type of CAM.
      Although CAM use did not affect the patients' quality of life, logistic
      regression analysis revealed that gender, type of cancer diagnosis and education
      level were important factors to be considered in different CAM therapies.
      CONCLUSION: CAM use is common in cancer patients in Turkey. More discussion about
      CAM use should take place between patients and health professionals to inform the
      patients' decisions.

PMID- 19395313
TI  - A systematic review evaluating the impact of post-registration nursing and
      midwifery education on practice.
AB  - Given the current focus on evidence-based practice, it is surprising that there
      is a dearth of systematic evidence of the impact on practice of post-registration
      nursing and midwifery education. The systematic review presented here formed part
      of a national review of post-registration nursing and midwifery education in
      Ireland [Health Service Executive, 2008. Report of the Post-registration Nursing
      and Midwifery Education Review Group: Changing practice to support service
      delivery. Health Service Executive, Dublin]. The review focuses specifically on
      the impact on practice from the perspective of nurses, midwives, patients,
      carers, education and health service providers. Sixty-one (61) studies met the
      criteria set. These studies were mainly of a retrospective and descriptive
      nature, often with small cohorts, set within one educational setting. The
      findings indicate that students benefit from post-registration programmes in
      relation to changes in attitudes, perceptions, knowledge and in skill
      acquisition. There is also some evidence that students apply their newly acquired
      attitudes, knowledge and skills. There is however limited evidence of the direct
      impact on organisational and service delivery changes, and on benefits to
      patients and carers. It can be concluded that the impact of post-registration
      nursing and midwifery education on practice has yet to be fully explored through
      a more systematic and coherent programme evaluation approach.

PMID- 19395314
TI  - The experiences and concerns of young adults (18-40 years) living with an
      implanted cardioverter defibrillator (ICD).
AB  - BACKGROUND: Although the implanted cardioverter defibrillator (ICD) is a widely
      accepted life-saving technology, adjusting to life after ICD implantation may
      vary according to the recipient's age. Few studies have investigated how young
      adults manage life with an ICD and there are no studies describing their concerns
      or experiences of living with an ICD. AIM: The aim of the study was to describe
      the experiences and concerns of young adults (18-40 years) living with an ICD.
      METHODS: Qualitative descriptive methodology was chosen incorporating interviews
      and written narrative responses to investigate twenty young adult's experiences
      of living with an ICD. RESULTS: There were four descriptive categories:
      psychosocial, developmental, physical, and economical. Themes in the psychosocial
      category were: returning to normal, mood disturbances, and body image concerns.
      Themes in the developmental category were unique to young adults: childbearing
      and childrearing, while themes in the physical category were expectation
      regarding physical activity, and the economical category, the issue of financial
      security. CONCLUSIONS: These data reveal that young adults with ICDs experience
      the unique concerns of childbearing, childrearing, and are worried about their
      financial security. These findings provide insight for the development of age
      appropriate interventions for young adults before and after ICD implantation.

PMID- 19395315
TI  - Search of regular sequences in promoters from eukaryotic genomes.
AB  - In this paper, the notion of "regularity" is introduced to describe the
      structural features of DNA sequences. This notion expands the "latent
      periodicity" term. The novel method for revealing regularity based on the runs
      test is described. The search of regular sequences in eukaryotic promoters has
      shown that more than 60% of them possess a regularity property on statistically
      significant level. Possible biological functions of regularity are discussed
      together with the possibility of using this characteristic for performing
      promoter annotation.

PMID- 19395316
TI  - IL-4 receptor as a bridge between the immune system and muscle in experimental
      myasthenia gravis I: up-regulation of muscle IL-15 by IL-4.
AB  - The study reported below describes increased expression of IL-4 receptor in
      cultured rat myocytes following exposure to an antibody reactive with the
      acetylcholine receptor (AChR). In addition, upon up-regulation of IL-4R, myocytes
      demonstrated an increased responsiveness to IL-4 by producing increased levels of
      IL-15. Moreover, following passive transfer of AChR antibody into Lewis rats,
      both the increased IL-4R expression and IL-15 production were also observed in
      intact skeletal muscle, co-localizing in particular individual muscle fibers; the
      same muscle fibers also produced the chemokine MCP-1 to which IL-4-producing T
      cells were attracted. A model is proposed in which these muscle activities
      participate in disease progression in experimental myasthenia gravis.

PMID- 19395317
TI  - IL-12 delivered intratumorally by multilamellar liposomes reactivates memory T
      cells in human tumor microenvironments.
AB  - Using a novel loading technique, IL-12 is reported here to be efficiently
      encapsulated within large multilamellar liposomes. The preclinical efficacy of
      the cytokine loaded liposomes to deliver IL-12 into human tumors and to reactive
      tumor-associated T cells in situ is tested using a human tumor xenograft model.
      IL-12 is released in vivo from these liposomes in a biologically active form when
      injected into tumor xenografts that are established by the subcutaneous
      implantation of non-disrupted pieces of human lung, breast or ovarian tumors into
      immunodeficient mice. The histological architecture of the original tumor tissue,
      including tumor-associated leukocytes, tumor cells and stromal cells is preserved
      anatomically and the cells remain functionally responsive to cytokines in these
      xenografts. The local and sustained release of IL-12 into the tumor
      microenvironment reactivates tumor-associated quiescent effector memory T cells
      to proliferate, produce and release IFN-gamma resulting in the killing of tumor
      cells in situ. Very little IL-12 is detected in the serum of mice for up to 5
      days after an intratumoral injection of the IL-12 liposomes. We conclude that IL
      12 loaded large multilamellar liposomes provide a safe method for the local and
      sustained delivery of IL-12 to tumors and a therapeutically effective way of
      reactivating existing tumor-associated T cells in human solid tumor
      microenvironments. The potential of this local in situ T cell re-stimulation to
      induce a systemic anti-tumor immunity is discussed.

PMID- 19395319
TI  - Accessibility of chromosomal recombination breaks in nuclei of wild-type and DNA
      PKcs-deficient cells.
AB  - V(D)J recombination is a highly regulated process, proceeding from a site
      specific cleavage to an imprecise end joining. After the DNA excision catalyzed
      by the recombinase encoded by recombination activating genes 1 and 2 (RAG1/2),
      newly generated recombination ends are believed held by a post-cleavage complex
      (PC) consisting of RAG1/2 proteins, and are subsequently resolved by non
      homologous end joining (NHEJ) machinery. The relay of these ends from PC to NHEJ
      remains elusive. It has been speculated that NHEJ factors modify the RAG1/2-PC to
      gain access to the ends or act on free ends after the disassembly of the PC.
      Thus, recombination ends may either be retained in a complex throughout the
      recombination process or left as unprotected free ends after cleavage, a
      condition that may permit an alternative, non-classical NHEJ end joining pathway.
      To directly test these scenarios on recombination induced chromosomal breaks, we
      have developed a recombination end protection assay to monitor the accessibility
      of recombination ends to exonuclease-V in intact nuclei. We demonstrate that
      these ends are well protected in the nuclei of wild-type cells, suggesting a
      seamless cleavage-joining reaction. However, divergent end protection of coding
      versus signal ends was found in cells derived from severe combined
      immunodeficient (scid) mice that are defective in the catalytic subunit of DNA
      dependent protein kinase (DNA-PKcs). While signal ends are resistant, opened
      coding ends are susceptible to enzymatic modification. Our data suggests a role
      of DNA-PKcs in protecting chromosomal coding ends. Furthermore, using
      recombination inducible scid cell lines, we demonstrate that conditional
      protection of coding ends is inversely correlated with the level of their
      resolution, i.e., the greater the accessibility of the coding ends, the higher
      level of coding joints formed. Taken together, our findings provide important
      insights into the resolution of recombination ends by error-prone alternative
      NHEJ pathways.

PMID- 19395320
TI  - Single-walled carbon nanotubes as an effective adsorbent in solid-phase
      microextraction of low level methyl tert-butyl ether, ethyl tert-butyl ether and
      methyl tert-amyl ether from human urine.
AB  - Carbon nanotubes (CNTs) are a kind of new carbon-based nano-materials which have
      drawn great attention in many application fields. The potential single-walled
      carbon nanotubes (SWCNTs) as solid-phase microextraction (SPME) adsorbents for
      the preconcentration of environmental pollutants have been investigated in recent
      years. The goal of this work was to investigate the feasibility of SWCNTs used as
      adsorbents for solid-phase microextraction of methyl tert-butyl ether (MTBE),
      ethyl tert-butyl ether (ETBE) and tert-amyl methyl ether (TAME) in human urine.
      SWCNTs were attached onto a stainless steel wire through organic binder.
      Potential factors affecting the extraction efficiency were optimized, including
      extraction time, extraction temperature, desorption time, desorption temperature,
      and salinity. The developed method showed good performance according to the ICH
      performance criteria for bioanalytical methods. The calibration curves of the
      ethers were linear (r(2)>or=0.992) in the range from 10 to 5000 ng L(-1). The
      limits of detection at a signal-to-noise (S/N) ratio of 3 were 10 ng L(-1) for
      all the analytes. In addition, compared with the commercial
      carboxen/polydimethylsiloxane (CAR/PDMS) fiber, the SWCNT fiber showed better
      thermal stability (over 350 degrees C) and longer life span (over 150 times). The
      developed method was applied successfully to determine trace level of the ethers
      in urine of 10 healthy male volunteers.

PMID- 19395318
TI  - DNA damage responses in Drosophila nbs mutants with reduced or altered NBS
      function.
AB  - The MRN complex, composed of MRE11, RAD50 and NBS, plays important roles in
      responding to DNA double-strand breaks (DSBs). In metazoans, functional studies
      of genes encoding these proteins have been challenging because complete loss-of
      function mutations are lethal at the organismal level and because NBS has
      multiple functions in DNA damage responses. To study functions of Drosophila NBS
      in DNA damage responses, we used a separation-of-function mutation that causes
      loss of the forkhead-associated (FHA) domain. Loss of the FHA domain resulted in
      hypersensitivity to ionizing radiation and defects in gap repair by homologous
      recombination, but had only a small effect on the DNA damage checkpoint response
      and did not impair DSB repair by end joining. We also found that heterozygosity
      for an nbs null mutation caused reduced gap repair and loss of the checkpoint
      response to low-dose irradiation. These findings shed light on possible sources
      of the cancer predisposition found in human carriers of NBN mutations.

PMID- 19395321
TI  - Dynamic lipidomics with stable isotope labelling.
AB  - Incorporation of stable isotope labelled precursors enables estimation of the
      kinetics of lipid synthesis and turnover (dynamic lipidomics) in the clinical as
      well the experimental setting. Recent advances in tandem mass spectrometry extend
      the analytical possibilities from measurements of isotope enrichments to
      determinations of intact substrates. Incorporations of deuteriated choline,
      ethanolamine and inositol can be determined by precursor and neutral loss scans
      of phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol,
      respectively. This experimental approach provides information on the kinetics of
      individual phospholipid molecular species and has considerable potential to probe
      diseases of lipid metabolism in vivo.

PMID- 19395322
TI  - Development and validation of a quantitative method for the determination of 12
      endocannabinoids and related compounds in human plasma using liquid
      chromatography-tandem mass spectrometry.
AB  - A sensitive and specific LC-MS/MS method for the quantification of the
      endocannabinoids and related structures anandamide, 2-arachidonoyl glycerol, 2
      arachidonyl glycerol ether, O-arachidonoyl ethanolamide, dihomo-gamma-linolenoyl
      ethanolamide, docosatetraenoyl ethanolamide, N-arachidonoyl dopamine, N
      arachidonyl glycine, N-oleoyl dopamine, oleoyl ethanolamide, palmitoyl
      ethanolamide, and stearoyl ethanolamide in human plasma was developed and
      validated. Compounds were extracted using acetonitrile followed by solid-phase
      extraction. Separation was performed on a Xterra C8 column using gradient elution
      coupled to a triple-quadrupole MS. LLOQ levels ranged from 0.02 to 1.75
      microg/mL, LODs ranged from 0.0002 to 0.1266 ng/mL, and accuracies were >80%
      (except stearoyl ethanolamide at lowest spike level) at all spike levels.

PMID- 19395323
TI  - A modified method for the determination of tobacco specific nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol in human urine by solid phase
      extraction using a molecularly imprinted polymer and liquid chromatography tandem
      mass spectrometry.
AB  - The work described in this paper represents an improvement over a previously
      published method for the determination of 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol (NNAL) in human urine by solid phase extraction on a molecularly
      imprinted polymer column coupled with HPLC and -MS/MS detection. The influence of
      ion suppression due to sample matrix effect was evaluated, and found to influence
      the response of NNAL. By changing the liquid chromatography conditions, the
      response for this method was enhanced approximately 25-fold through avoidance of
      ionization suppression that was found with a previously published method and
      sample throughput has been improved. The dynamic range of the assay extends from
      20 to 2500 pg/mL with a mean r(2)>0.998. The lower limit of quantitation for the
      assay was 20 pg/mL despite the use of an inherently lower sensitivity instrument.
      The method was validated according to current FDA guidelines for bioanalytical
      method validations.

PMID- 19395324
TI  - Determination of chloramphenicol, thiamphenicol, florfenicol, and florfenicol
      amine in poultry and porcine muscle and liver by gas chromatography-negative
      chemical ionization mass spectrometry.
AB  - A sensitive and reliable method using gas chromatography-negative chemical
      ionization mass spectrometry (GC-NCI/MS) was developed for the simultaneous
      determination of chloramphenicol (CAP), thiamphenicol (TAP), florfenicol (FF),
      and florfenicol amine (FFA) at trace levels in muscle and liver. Before
      extraction with ethyl acetate, CAP-d(5) was added to tissue samples as internal
      standard. The organic extracts were frozen to remove lipid and further purified
      by liquid-liquid extraction (LLE) with hexane and solid-phase extraction (SPE)
      using Oasis HLB cartridges. The target compounds were derivatized with BSTFA+1%
      TMCS prior to GC-NCI/MS determination in selected ion monitoring mode (SIM). The
      recovery values ranged from 78.5 to 105.5%, with relative standard deviations
      (RSD) <17%. The limits of detections (LODs) of 0.1 microg/kg for CAP and 0.5
      microg/kg for TAP, FF, and FFA were obtain. Incurred sample and samples from
      local market were successfully analyzed using this method.

PMID- 19395325
TI  - Purification of histidine-tagged nucleocapsid protein of Nipah virus using
      immobilized metal affinity chromatography.
AB  - Nucleocapsid (N) protein of Nipah virus (NiV) is a potential serological marker
      used in the diagnosis of NiV infections. In this study, a rapid and efficient
      purification system, HisTrap 6 Fast Flow packed bed column was applied to purify
      recombinant histidine-tagged N protein of NiV from clarified feedstock. The
      optimizations of binding and elution conditions of N protein of NiV onto and from
      Nickel Sepharose 6 Fast Flow were investigated. The optimal binding was achieved
      at pH 7.5, superficial velocity of 1.25 cm/min. The bound N protein was
      successfully recovered by a stepwise elution with different concentration of
      imidazole (50, 150, 300 and 500 mM). The N protein of NiV was captured and eluted
      from an inlet N protein concentration of 0.4 mg/ml in a scale-up immobilized
      metal affinity chromatography (IMAC) packed bed column of Nickel Sepharose 6 Fast
      Flow with the optimized condition obtained from the method scouting. The
      purification of histidine-tagged N protein using IMAC packed bed column has
      resulted a 68.3% yield and a purification factor of 7.94.

PMID- 19395326
TI  - Growing up under generalized violence: an ecological study of homicide rates and
      secular trends in age at menarche in Colombia, 1940s-1980s.
AB  - We examined secular changes in mean age at menarche among 5577 Colombian women
      born between 1941 and 1989, and correlated those changes with nation-wide rates
      of homicide and real gross domestic product per capita (GDP) at the year of birth
      and at the year at age 5, within predefined historical periods. The mean
      (standard error) rate of change in age at menarche by year of birth was -0.55
      (0.02) years/decade. The rate of change was not constant, but varied between
      historical periods as follows: -1.44, -0.14, -0.60, and -0.36 years/decade for
      the periods 1941-1947, 1948-1958, 1959-1978, and 1979-1989, respectively. The
      changes in age at menarche correlated positively with the changes in the nation
      wide rates of homicide within such periods; i.e. decelerations in the menarcheal
      trend coincided with increases in the rates of homicide and vice versa. The
      correlation was higher with the rates of homicide when women were 5 years of age
      (r=0.99, p=0.01) compared to the rates of homicide at the year of birth (0.55,
      p=0.45). There were negative correlations between the changes in age at menarche
      and the changes in GDP, but they were weaker than those with the rates of
      homicide. These results could suggest a potential impact on maturation of
      psychosocial stress in childhood due to exposure to a generalized atmosphere of
      violence and fear.

PMID- 19395327
TI  - Early pregnancy loss in celiac women: The role of genetic markers of
      thrombophilia.
AB  - BACKGROUND: Adverse pregnancy outcomes are more frequent in celiac than in non
      celiac women. AIMS: To investigate a possible role of genetic prothrombotic
      variants in early pregnancy loss of celiac women. METHODS: Thirty-nine celiac
      women who had experienced early pregnancy losses (at least two losses within the
      first 3 months of pregnancy), and 72 celiac women with a history of one or more
      normal pregnancies and no pregnancy loss (controls) entered the study, at the
      moment of diagnosis for celiac disease. A clinical history was obtained from each
      woman. DNA from leukocytes was tested for: factor V Leiden (mutation G1691A),
      factor V R2 (H1299R), factor II (G20210A), methylenetetrahydrofolate reductase
      (MTHFR) (C677T and A1298C), beta-fibrinogen (-455 G>A), PAI-1 alleles 4G/5G,
      factor XIII (V34L), and HPA-1 (L33P). RESULTS: Age at diagnosis was significantly
      higher (p=0.002) in the celiac women with pregnancy losses than in controls. Of
      the gene variants studied, the allelic frequency of 4G variant of PAI-1, and the
      frequency of mutant genotypes were significantly more frequent in the group of
      celiac women with early pregnancy loss (p=0.00003 and 0.028, respectively).
      Surprisingly, the beta-fibrinogen -455 G>A genotype distribution (but not the
      allelic frequency of the variant allele) significantly differed between the two
      groups, since variant genotypes were more frequent in the control group
      (p=0.009). CONCLUSION: The 4G variant of the PAI-I gene may predispose to
      miscarriage a subset of celiac women; these data should be verified on larger
      populations.

PMID- 19395328
TI  - [Epistaxis in childhood: not always an insignificant finding].

PMID- 19395329
TI  - Fascicular turnover flap for nerve gaps.
AB  - BACKGROUND: It is well known that free vascularised nerve grafts have a potential
      for rapid axonal sprouting. However, they are not very popular as the surgical
      techniques are complicated. With the recent development of supramicrosurgical
      techniques and microanatomy of nerve trunks, a new method, 'fascicular turnover
      method', using vascularised fascicular flap was used for repairing nerve gaps.
      METHODSAND RESULTS: Arterial embalming method, using rat sciatic nerves, was
      employed to observe fascicular micro-vascularisation. Rich vascular network
      systems were observed within and outside the rat island nerve flaps. Four cases
      with digital and facial nerves gaps were repaired with fascicular turnover flap
      without a nerve graft. Three patients had digital nerve gaps (10-20mm in length)
      and one had a 3-cm facial nerve gap. The results of sensory recovery of digital
      nerve gap were 3.22-3.66 (Semmes-Weinstein values) and 6-12mm (moving two-point
      discriminations) at 6 and -16 months after surgery, respectively. CONCLUSION: The
      advantages of this method are: retention of the normal donor nerve, a shorter
      operation time and repair of the digital nerve gaps under local anaesthesia.
      Fascicular flap is a vascularised nerve flap with fast and accurate nerve
      sprouting in comparison to a non-vascularised graft. Excellent nerve regeneration
      can be expected even in cases with longer nerve gap and scarred recipient bed. It
      is a simple and quick surgery compared to free vascularised nerve flaps. In
      addition, there is no functional loss because of the sacrificed fascicle in the
      operated area. The only disadvantage is the need to employ superficial palmar
      branch of radial artery (SPRA)-microsurgical techniques using a 50-micron needle.

PMID- 19395330
TI  - Safe and less painful injection of triamcenolone acetonide into a keloid--a
      technique.

PMID- 19395331
TI  - Vitamin D and type 2 diabetes: Is there a link?
AB  - Prevention, or at least delay in onset of type 2 diabetes is possible by
      intensive lifestyle intervention. This is costly and labour intensive, and
      alternative methods of preventing diabetes have been sought. Vitamin D has
      important physiological effects aside from its effects on bone metabolism,
      including an important role in glucose homeostasis, insulin release and response.
      Observational data strongly support the role of vitamin D deficiency in the
      pathogenesis of type 2 diabetes. The time is ripe for a well conducted randomised
      controlled trial of vitamin D in high risk individuals to test the hypothesis
      that vitamin D delays the onset of type 2 diabetes.

PMID- 19395332
TI  - Effect of routine cardiovascular catheterization on cardiac troponin I
      concentration in dogs.
AB  - OBJECTIVE: To determine changes in cardiac troponin I concentration (cTnI)
      associated with cardiovascular catheterization in dogs. ANIMALS, MATERIALS AND
      METHODS: cTnI was measured after transarterial coil embolization of patent ductus
      arteriosus (PDA), balloon valvuloplasty (BV), and pacemaker implantation (PACE).
      Dogs undergoing ovariohysterectomy (OHE) were used as a control, with 15 animals
      in each group. Blood for the cTnI assay was collected at baseline (T0), at 5h
      (T5), 24h (T24) and 10 days (T240) post-procedure. The effects of age, duration
      and difficulty of the procedure were evaluated. RESULTS: There was no difference
      in cTnI concentration at T0 for any of the groups. There was a significant
      increase in cTnI concentration for BV and PACE, but not PDA at T5 and T24. PACE
      at T24 and T240 also had higher cTnI than control. Dogs with longer procedure
      times had significantly higher concentration of cTnI. There was no correlation
      between the difficulty of the procedure or peri-procedure complications and cTnI.
      CONCLUSION: cTnI increased during some cardiovascular catheterization procedures,
      but returned to normal values at 24-240 h. Patients undergoing long
      catheterization procedures have increased risk for myocardial injury, but this
      was not related to short-term prognosis.

PMID- 19395333
TI  - Biomarkers in cardiovascular disease: beyond natriuretic peptides.
AB  - Currently natriuretic peptides are justifiably regarded as the most promising
      circulating markers of cardiovascular disease in dogs and cats, but there are
      many other markers that can be used in the evaluation of such patients. There are
      markers of myocyte injury typified by troponins I and T; markers of myocyte
      stress including adrenomedullin and ST2; markers of remodeling including matrix
      metalloproteinases, tissue inhibitors of metalloproteinases and collagen
      molecules (PIIINP); markers of endothelial function including dimethylarginines
      and nitric oxide metabolites; markers of inflammation including C-reactive
      protein, several interleukins and tumor necrosis factor alpha; and finally
      neurohormonal markers. The potential of many of these markers has at best been
      only partially explored in veterinary patients. Evidence emerging from studies of
      human and in some cases veterinary patients suggests that using multiple markers
      may be superior to using single markers alone. As well as evaluating markers for
      their diagnostic value they should be considered as methods of identification of
      patients at increased risk of experiencing complications or death. Future areas
      of research in this field could include improved characterization of the clinical
      utility of multi-marker evaluation in veterinary patients and using markers to
      identify patients that may benefit from particular interventions.

PMID- 19395334
TI  - Investigation into the use of plasma NT-proBNP concentration to screen for feline
      hypertrophic cardiomyopathy.
AB  - OBJECTIVE: To evaluate the utility of feline NT-proBNP plasma concentration [NT
      proBNP] as a screening tool for cats with subclinical hypertrophic cardiomyopathy
      (HCM). ANIMALS, MATERIALS AND METHODS: Forty adult Maine Coon or Maine Coon
      crossbred cats from the feline HCM research colony at the University of
      California, Davis were studied. All cats had previously been genotyped as
      heterozygous or negative for the A31P myosin binding protein C (MYBPC) mutation.
      Echocardiograms were performed to assess the severity of HCM in each cat. Blood
      samples were collected for evaluation of [NT-proBNP]. RESULTS: In these cats with
      severe HCM, [NT-proBNP] was significantly elevated (P<0.0001) when compared to
      all other groups of cats and an [NT-proBNP]>44pmol/L accurately predicted the
      presence of severe HCM. However, [NT-proBNP] was not increased in cats with
      moderate or equivocal HCM when compared to normal cats. Cats heterozygous for the
      MYBPC mutation had a significantly elevated [NT-proBNP] when compared to cats
      without the A31P mutation (P=0.028). CONCLUSIONS: Measurement of [NT-proBNP] has
      a high sensitivity and specificity as a means of detecting severe HCM in cats,
      but it is not sensitive for the identification of moderate HCM as judged by the
      evaluation of Maine Coon and Maine Coon cross cats in our colony. Consequently,
      we conclude that this test cannot be used to screen cats for the presence of mild
      to moderate HCM.

PMID- 19395335
TI  - Weekly variability of plasma and serum NT-proBNP measurements in normal dogs.
AB  - OBJECTIVES: To determine the weekly variability of serum and plasma N-terminal
      pro-B-type natriuretic peptide (NT-proBNP) concentrations in healthy dogs.
      ANIMALS, MATERIALS AND METHODS: Fifty-three normal dogs were examined
      prospectively. Serum (n=25) or plasma (n=28) samples were obtained for NT-proBNP
      assay at one week interval for 3 consecutive weeks. RESULTS: Median serum or
      plasma NT-proBNP concentration did not change over 3 consecutive weeks. Twenty
      two of 53 dogs (42%) had at least one NT-proBNP value >500 pmol/L, including 14
      dogs with at least one serum NT-proBNP concentration >500 pmol/L and 8 dogs with
      at least one plasma NT-proBNP concentration >500 pmol/L during the 3-week
      sampling period. The difference between the maximum and minimum NT-proBNP value
      obtained over the 3-week sampling period was <100 pmol/L in 40% of dogs, between
      100 and 200 pmol/L in 40% of dogs, and >200 pmol/L in 20% of dogs. Of the 19 dogs
      with a value >500 pmol/L on either week 1 or 2, 11 dogs (58%) had a subsequent NT
      proBNP value <500 pmol/L on either week 2 or 3. CONCLUSIONS: There is a high
      degree of variability in weekly serum and plasma NT-proBNP values in healthy
      dogs. Individual variability should be considered when interpreting NT-proBNP
      results in dogs.

PMID- 19395337
TI  - Delivery of peptide and protein drugs over the blood-brain barrier.
AB  - Peptide and protein (P/P) drugs have been identified as showing great promises
      for the treatment of various neurodegenerative diseases. A major challenge in
      this regard, however, is the delivery of P/P drugs over the blood-brain barrier
      (BBB). Intense research over the last 25 years has enabled a better understanding
      of the cellular and molecular transport mechanisms at the BBB, and several
      strategies for enhanced P/P drug delivery over the BBB have been developed and
      tested in preclinical and clinical-experimental research. Among them, technology
      based approaches (comprising functionalized nanocarriers and liposomes) and
      pharmacological strategies (such as the use of carrier systems and chimeric
      peptide technology) appear to be the most promising ones. This review combines a
      comprehensive overview on the current understanding of the transport mechanisms
      at the BBB with promising selected strategies published so far that can be
      applied to facilitate enhanced P/P drug delivery over the BBB.

PMID- 19395336
TI  - Salmonella enterica subsp. arizonae bone and joints sepsis. A case report and
      literature review.
AB  - Osteoarticular infections caused by Salmonella enterica subsp. arizonae are
      rarely seen in humans but young children and immunocompromised adults are at
      particular risk of acquiring this bacteria. Reptiles and their by-products (e.g.
      meat preparations or medications) are particularly likely to harbor Salmonella.
      We report on a case of septic arthritis of the hip transmitted by a reptile in a
      10-month-old child. We carry out a recall of the complex nomenclature of
      Salmonella, a review of the literature and provide information on the recommended
      precautions for reducing the risk of transmission of Salmonella from reptiles to
      humans.

PMID- 19395338
TI  - Emerging contaminants in drinking water: what to do?

PMID- 19395339
TI  - Effects of a unique electromagnetic field system on the fertility of rats.
AB  - The authors investigated the fertility of male and female rats exposed to a
      unique-design electromagnetic apparatus (Hivex Electromagnetic Field System-5
      [EMFS-5]), which establishes an omni-directional, spatial field and has a wide
      band range of 100 MHz-3 GHz. We used 32 male and 32 female rats that were proven
      breeders. Sixteen rats from each sex were exposed to the EMFS for 8h/day for 10
      days. The others were sham exposed. The rats were divided into the following 4
      groups: in group AG1-AG8, males and females were exposed; in group AG9-AG16, only
      females were exposed; in group AG17-AG24, only males were exposed; and in group
      AG25-AG32, males and females were sham exposed. After exposure for each group, a
      male rat was cohabited with a female rat until parturition. The authors' results
      showed that except for 1 male, the fertility of all other rats was not affected.
      They did not see differences in reproductive ability (latency to parturition,
      litter size, number of male/female pups, male-to-female ratio, mass of pups at
      weaning) between experimental groups and the sham exposed group. The authors
      concluded that exposure of male and female rats to the Hivex EMFS-5 does not
      affect fertility or reproductive ability.

PMID- 19395340
TI  - The prevalence of chromosomal aberrations in Argentine air crew members.
AB  - The authors analyzed the effects of chronic exposure of Argentine air crew
      members to low doses of ionizing radiations. Genetic damage induced by either low
      doses or low rates of ionizing radiation was higher than expected. Seventy-one
      heparinized blood samples were obtained from technical ground workers (group A; n
      = 10), pilots of domestic flights (group B; n = 14), pilots of transequatorial
      flights (group C; n = 17;), pilots of transpolar flights (group D; n = 17) and
      retired pilots (group E; n = 10) The frequency of dicentric chromosomes was
      higher in groups B and C compared with groups D and E. These observations suggest
      that the exposure of the aircraft to ionizing radiations may induce chromosomal
      aberrations. However, dicentric chromosomes in both domestic and retired pilots
      are still high compared with dicentric control participants.

PMID- 19395341
TI  - Chinese immigrant restaurant workers' injury and illness experiences.
AB  - Restaurants are an important source of employment for immigrants in the United
      States. This article discusses the findings from an ethnographic study on Chinese
      immigrant restaurant workers' occupational injury and illness experiences.
      Eighteen participants were interviewed; 10 of whom attended follow-up focus
      groups. The author used ethnographic content analysis to analyze the data. On-the
      job cuts and burns were the most common injuries. Musculoskeletal disorders, or
      specifically aches and pains, soreness, or numbness were the most troubling
      occupational illnesses. The author identified three cultural concepts pertinent
      to the causes of occupational illnesses during data analysis. Participants used
      multiple methods to heal their injuries and illnesses and to keep themselves safe
      and healthy. Implications for cultural competence in US occupational safety and
      health research and practice and elimination of health disparities in immigrant
      workers conclude the article.

PMID- 19395342
TI  - Lead exposure among target shooters.
AB  - The New York State Heavy Metals Registry receives reports on all New Yorkers
      tested for lead. The Registry was reviewed for information on individuals who had
      lead exposure from target shooting. Overall, 598 individuals have been reported
      with exposures from target shooting. Over one-half had nonoccupational exposures.
      These individuals were reported more frequently with elevated blood lead levels
      (over 40 microg/dL) than those with occupational exposures. Hobby target shooters
      are at significant risk of having elevated blood lead levels. Because of the
      potential for serious lead exposure as a result of target shooting, efforts
      should be made to inform target shooters of the health risks and methods that can
      reduce exposure to themselves, other range users, and their families.

PMID- 19395343
TI  - Challenges facing female physicians in Egypt.
AB  - The number of female physicians all over the world has grown considerably, yet
      little is known about these women. This study was conducted to explore challenges
      faced by Egyptian female physicians as they pursue their careers and find
      different ways of coping with these challenges. The mean age of participants was
      31.09 years (SD = 6.46 years). Most of them were married (76.7%), and 40% were
      part of dual-doctor families (both partners were physicians). In all, 53% of
      participants were clinicians, 22% academics, and 25% house officers. All
      academics had no shift work compared with all house officers and 75% of
      clinicians. Challenges reported by physicians were either work or family related.
      Although overt discrimination was rare, many participants complained of subtle
      forms of bias. All participants reported that balancing work and family was more
      difficult than they ever expected. Participating physicians have dealt with
      challenges in different ways: deciding on a small family size (82.3%), the
      recruitment of a babysitter/housekeeper (76.3%), and sharing in the family income
      (62.0%). Physician training programs, workforce policy, and public expectations
      should recognize and adapt to the diverse and changing needs of physicians.

PMID- 19395344
TI  - Harmful algal bloom-associated marine toxins: a risk assessment framework.
AB  - Marine toxins produced by harmful algal blooms (HABs) present a health risk to
      humans, but the extent of that risk remains unquantified. Increases in bloom
      frequency and geographic distribution present a potential for increased human
      exposure to these toxins, raising concerns among HAB researchers regarding an
      emerging public health problem. A risk assessment framework is presented with 2
      objectives: (1) to provide a road map for integration and coordination of health
      related research efforts and (2) to provide an overview of this complex problem
      to possible collaborators.

PMID- 19395346
TI  - Bilateral primary pterygia: an occupational disease?
AB  - The authors report on a case of bilateral pterygia that the Israeli Social
      Security Service acknowledged to be an occupational disease. The question of
      whether certain occupations are risk factors for pterygia has important medico
      legal implications. The authors sought to shed more light on this issue through a
      case report of bilateral simultaneous pterygia in an Israeli tennis instructor
      and through a literature review. Results indicate that most studies show a strong
      relation between pterygia formation and outdoor work with exposure to UV rays.
      Also, the patient refused to use protective eyewear during his long outdoor
      working hours and, by doing so, exposed his eyes to excessive sunlight, which led
      to occupational disease.

PMID- 19395345
TI  - Ocular injury with high-pressure paint: a case report.
AB  - Chemical injury to the eye is an ophthalmic emergency that can be caused by a
      work-related accident or common household products. Uradil SZ261 G3Z-65 is a
      resin containing butyl gycol (2-butoxyethanol) and ethyl ethanol amine (2
      dimethyaminoethanol). It is used in stoving enamels for interior and exterior
      use. The authors report a case of ocular surface injury with a highpressure
      industrial spray paint-Waterborne Stoving Gentian Blue containing Uradil.

PMID- 19395347
TI  - Chairing a session at a scientific meeting.

PMID- 19395348
TI  - The Medical Symptom Validity Test in the evaluation of Operation Iraqi
      Freedom/Operation Enduring Freedom soldiers: a preliminary study.
AB  - The clinical utility of the Medical Symptom Validity Test (MSVT) for soldiers
      returning from service in Operation Iraqi Freedom or Operation Enduring Freedom
      was preliminarily investigated through retrospective chart review. Results showed
      that 17%, or 4 of 23, Operation Iraqi Freedom/Operation Enduring Freedom patients
      at a Polytrauma Network Site (Level 2), performed below cut-offs on the MSVT. On
      "easy" subtests of the MSVT, the group of individuals who failed the MSVT
      performed significantly worse than the group of individuals who passed. However,
      there were no significant group differences on the "hard" subtests of the MSVT.
      When the profiles of individuals who failed the MSVT were examined, none of them
      met the criteria for the Dementia Profile. These preliminary findings and
      additional test data supported the conclusion that participants who failed the
      MSVT were exhibiting diminished symptom validity, suggesting that the specificity
      of the MSVT was 100%.

PMID- 19395350
TI  - Validity of the CogState brief battery: relationship to standardized tests and
      sensitivity to cognitive impairment in mild traumatic brain injury,
      schizophrenia, and AIDS dementia complex.
AB  - This study examined the validity of the four standard psychological paradigms
      that have been operationally defined within the CogState brief computerized
      cognitive assessment battery. Construct validity was determined in a large group
      of healthy adults. CogState measures of processing speed, attention, working
      memory, and learning showed strong correlations with conventional
      neuropsychological measures of these same constructs (r's = .49 to .83).
      Criterion validity was determined by examining patterns of performance on the
      CogState tasks in groups of individuals with mild head injury, schizophrenia, and
      AIDS dementia complex. Each of these groups was impaired on the CogState
      performance measures (Cohen's d's = -.60 to -1.80) and the magnitude and nature
      of this impairment was qualitatively and quantitatively similar in each group.
      Taken together, the results suggest that the cognitive paradigms operationally
      defined in the CogState brief battery have acceptable construct and criterion
      validity in a neuropsychological context.

PMID- 19395349
TI  - Professional considerations for improving the neuropsychological evaluation of
      Hispanics: a National Academy of Neuropsychology education paper.
AB  - In a national survey, 82% of U.S. neuropsychologists who offered services to
      Hispanics self-reported inadequate preparation to work with this population
      (Echemendia, Harris, Congett, Diaz, & Puente, 1997). The purpose of this paper is
      to improve the quality and accessibility of neuropsychological services for
      Hispanic people living in the United States by giving guidance for service
      delivery, training, and organizational policy. General guidance towards this end
      comes from professional ethics for psychologists and interpreters/translators,
      federal civil rights law, the International Test Commission, and the Office of
      Minority Health of the U.S. Department of Health and Human Services, among
      others. This guidance is specifically applied here to cover professional cultural
      and linguistic competence of neuropsychologists, psychometrists, interpreters,
      translators, and consultants; languages of evaluation; use of interpreters;
      evaluation of acculturation; test translation, adaptation, and interpretation;
      application of test norms; intervention issues; reimbursement; and organizational
      issues.

PMID- 19395351
TI  - Secretive recording of neuropsychological testing and interviewing: official
      position of the National Academy of Neuropsychology.
AB  - Neuropsychologists are occasionally asked to have neuropsychological testing
      observed via the presence of a third party, through one-way mirrors, or with
      audio or video monitoring or recording devices. The primary reasons for not
      allowing observation are its effect on the validity of the examination results
      and the security of copyrighted test materials. To overcome the problem of
      observer effects on the examinee's performance, some individuals have suggested
      that examinations be monitored or recorded without the examinee's awareness
      (i.e., secretly). However, secretive recording of neuropsychological interviews
      and testing is deceptive, which is inconsistent with ethical principles. In
      addition, such recording may affect the behavior of the examiner. For these
      reasons, neuropsychologists do not, and should not, encourage, condone, or engage
      in secret recording of neuropsychological interviews or testing.

PMID- 19395353
TI  - Neuropsychological consequences of boxing and recommendations to improve safety:
      a National Academy of Neuropsychology education paper.
AB  - Boxing has held appeal for many athletes and audiences for centuries, and
      injuries have been part of boxing since its inception. Although permanent and
      irreversible neurologic dysfunction does not occur in the majority of
      participants, an association has been reported between the number of bouts fought
      and the development of neurologic, psychiatric, or histopathological signs and
      symptoms of encephalopathy in boxers. The purpose of this paper is to (i) provide
      clinical neuropsychologists, other health-care professionals, and the general
      public with information about the potential neuropsychological consequences of
      boxing, and (ii) provide recommendations to improve safety standards for those
      who participate in the sport.

PMID- 19395352
TI  - Recommendations for diagnosing a mild traumatic brain injury: a National Academy
      of Neuropsychology education paper.
AB  - A special interest group of the American Congress of Rehabilitation Medicine
      [ACRM; Mild Traumatic Brain Injury Committee. (1993). Definition of mild
      traumatic brain injury. Journal of Head Trauma Rehabilitation, 8 (3), 86-87.] was
      the first organized interdisciplinary group to advocate four specific criteria
      for the diagnosis of a mild traumatic brain injury (TBI). More recently, the
      World Health Organization (WHO) Collaborative Center Task Force on Mild Traumatic
      Brain Injury [Carroll, L. J., Cassidy, J. D., Holm, L., Kraus, J., & Coronado, V.
      G. (2004). Methodological issues and research recommendations for mild traumatic
      brain injury: the WHO Collaborating Centre Task Force on Mild Traumatic Brain
      Injury. Journal of Rehabilitation Medicine, (Suppl. 43), 113-125.] conducted a
      comprehensive review of the definitions utilized in evidence-based studies with
      mild TBI patients. Based on this review, the WHO task force maintained the same
      four criteria but offered two modifications. The similarities and differences
      between these two definitions are discussed. The authors of the ACRM and the WHO
      definitions do not provide guidelines or specific recommendations for diagnosing
      the four criteria. Thus, we provide recommendations for assessing loss of
      consciousness, retrograde and post-traumatic amnesia, disorientation and
      confusion as well as clarification of the neurologic signs that can be indicative
      of a diagnosis of mild TBI. Finally, confounding factors mentioned in both
      definitions that should exclude a mild TBI diagnosis are summarized.

PMID- 19395354
TI  - Beyond the numbers: expanding the boundaries of neuropsychology.
AB  - Beyond the Numbers: Expanding the Boundaries of Neuropsychology was Dr Perry's
      2007 presidential address in the annual conference of the National Academy of
      Neuropsychology. In his address he discussed the achievements of the science of
      neuropsychology and highlighted some areas that exemplified the expansion of the
      boundaries of neuropsychology. These areas are: (i) the study of
      neuropsychological functioning in new or non-traditional populations,
      particularly seemingly healthy people and people with non-brain diseases; (ii)
      the interface of cognition and genetics; (iii) the use of the process approach as
      a means of understanding brain functioning; and (iv) a translational application
      to the science of neuropsychology.

PMID- 19395355
TI  - To err is human: "abnormal" neuropsychological scores and variability are common
      in healthy adults.
AB  - Normative studies of variability in performance by healthy adults on
      neuropsychological batteries are reviewed. Regarding test score scatter,
      normative participants often have large discrepancies between best and worst
      scores. When "abnormality" was defined as a score more than one standard
      deviation below the mean, in test batteries with at least 20 measures, the great
      majority of normative participants had one or more abnormalities. Restricting
      samples to participants with above average IQ or educational levels and using
      more conservative definitions of abnormality, such as two standard deviations
      below the mean did not eliminate the presence of abnormal scores. We conclude
      that abnormal performance on some proportion of neuropsychological tests in a
      battery is psychometrically normal. Abnormalities do not necessarily signify the
      presence of acquired brain dysfunction because low scores and large
      intraindividual variability often are characteristic of healthy adults. We
      recommend that test battery developers provide data on the amount of variability
      in normal samples and also provide base rate tables with false positive rates
      that can be used clinically when interpreting test performance.

PMID- 19395356
TI  - Examining the link between information processing speed and executive functioning
      in multiple sclerosis.
AB  - Slowed information processing speed (IPS) is frequently reported in those with
      multiple sclerosis (MS), and at least 20% are compromised on some aspect of
      executive functioning also. However, any relationship between these two processes
      has not been examined. The Sternberg Memory Scanning Test, Processing Speed Index
      (WAIS-III), Delis Kaplan Executive Function System (D.KEFS), and Working Memory
      Index (WMS-III) were administered to 90 participants with MS. Their performance
      on the PSI was significantly below the normative scores but no deficits in memory
      scanning speed were evident. The initial response speed of the Sternberg and the
      PSI were more closely related to D.KEFS performance, particularly in timed tasks
      with a high cognitive demand (switching tasks). In contrast, memory scanning
      speed was related to working memory. This study reinforces the link between IPS
      and working memory in MS, and supports the suggestion that IPS is not a unitary
      construct.

PMID- 19395357
TI  - Development of a novel malingering detection method involving multiple detection
      strategies.
AB  - This study utilized a novel computer-administered measure designed to assess
      multiple malingering detection strategies, as well as measure genuine impairment
      in a brain-injured sample. Ninety-four neurologically normal subjects comprised
      control and simulator groups. Twenty individuals with moderate to severe head
      injuries comprised a clinical sample. The summary score from the measure yielded
      a sensitivity of .81 and a specificity of .89. Total completion time and learning
      curves were utilized as genuine impairment indicators. Sensitivity (.95) and
      specificity (.95) were quite high for these dimensions. Results suggest there is
      utility to combining detection techniques, including indicators of genuine
      impairment.

PMID- 19395358
TI  - The stroop effect in Greek healthy population: normative data for the Stroop
      Neuropsychological Screening Test.
AB  - The Stroop Test is a quick and frequently used measure in screening for brain
      damage, dysfunction of selective attention, and cognitive flexibility. The
      purpose of the present study is to provide normative data for Trenerry's Stroop
      Neuropsychological Screening Test (SNST) in a sample of 605 healthy Greek
      participants (age range: 18-84 years, education range: 6-18 years). Results
      revealed that age and education significantly contributed to SNST scores,
      accounting for a significant proportion of variance in time needed to complete
      the color task and in the interference Color-Word score. Performance on most of
      the measures decreases with increasing age and lower levels of education.
      Normative data stratified by age and education for the Greek adult population are
      provided as a useful set of norms for clinical practice.

PMID- 19395359
TI  - The comprehensive affect testing system-abbreviated: effects of age on
      performance.
AB  - Deficits in the ability to recognize emotions in others have been noted in a wide
      variety of disorders, ranging from the psychiatric to the neurologic. Emotions
      are vital to social interactions, yet there are currently few standardized
      neuropsychological measures in common use to assess emotion perception abilities.
      This study examined the effects of age on performance of the Comprehensive Affect
      Testing System, a new assessment battery designed to measure perception of
      emotion via facial affect, prosody, and semantic content. Age was not associated
      with a significant decline in performance on facial tasks, although there was a
      significant age effect when discrete emotions were examined. Age was strongly
      associated with a decline in performance on prosody and cross-modal tasks, and
      this decline was independent of the decline in fluid ability that also
      accompanies the aging process. The results underscore the need for standardized
      instruments to assess emotion recognition abilities.

PMID- 19395360
TI  - Interference effects on commonly used memory tasks.
AB  - This paper reports two studies which investigated the effect of interference on
      delayed recall scores of the WMS-III and other commonly used memory measures. In
      Study 1, participants completed the immediate and delayed components of the WMS
      III, with or without the introduction of conceptually similar memory tasks
      between the recall trials. In Study 2, this order of administration was reversed,
      with the WMS-III subtests used as the interference items. The results indicated
      that the introduction of interference items during the delay negatively affected
      delayed recall performance on almost all sub-tests. In addition, equal effects of
      proactive and retroactive interference were demonstrated. These findings raise
      concerns regarding the standardization process for memory tasks and highlight the
      need to consider interference effects in clinical practice, and stand as a
      caution in the use of memory-related materials during the delay interval in
      memory testing.

PMID- 19395361
TI  - Executive function and decision-making in women with fibromyalgia.
AB  - Patients with fibromyalgia (FM) typically report cognitive problems, and they
      state that these deficits are disturbing in everyday life. Despite these
      substantial subjective complaints by FM patients, very few studies have addressed
      objectively the effect of such aversive states on neuropsychological performance.
      In this study we aimed to examine possible impairment of executive function and
      decision-making in a sample of 36 women diagnosed with FM and 36 healthy women
      matched in age, education, and socio-economic status. We contrasted performance
      of both groups on two measures of executive functioning: the Wisconsin Card
      Sorting Test (WCST), which assesses cognitive flexibility skills, and the Iowa
      Gambling Tasks (IGT; original and variant versions), which assess emotion-based
      decision-making. We also examined the relationship between executive function
      performance and pain experience, and between executive function and personality
      traits of novelty-seeking, harm avoidance, reward dependence, and persistence
      (measured by the Temperament and Character Inventory-Revised). Results showed
      that on the WCST, FM women showed poorer performance than healthy comparison
      women on the number of categories and non-perseverative errors, but not on
      perseverative errors. FM patients also showed altered learning curve in the
      original IGT (where reward is immediate and punishment is delayed), suggesting
      compromised emotion-based decision-making; but not in the variant IGT (where
      punishment is immediate but reward is delayed), suggesting hypersensitivity to
      reward. Personality variables were very mildly associated with cognitive
      performance in FM women.

PMID- 19395362
TI  - Endocannabinoids and reproductive biology.

PMID- 19395363
TI  - Assessment of a new in vitro maturation system for mouse and human cumulus
      enclosed oocytes: three-dimensional prematuration culture in the presence of a
      phosphodiesterase 3-inhibitor.
AB  - BACKGROUND: Controlling nuclear maturation during oocyte culture might improve
      nuclear-cytoplasmic maturation synchrony. In the present study, the quality of
      mouse and human cumulus-enclosed oocytes (CEOs) was examined after a two-step
      culture consisting of a three-dimensional prematuration culture (3D-PMC),
      followed by in vitro maturation (IVM). METHODS: Mouse and human CEOs were
      embedded in an extracellular matrix (collagen-gel Type I). The gels containing
      the CEOs were cultured in medium with a phosphodiesterase 3-inhibitor (PDE3-I;
      cilostamide 1 microM) for 24 h. Afterwards, CEOs were removed from the gel and
      washed away from inhibitor then underwent IVM. The optimal concentration of
      collagen (diluted 1:2 versus not-diluted) was first determined in the mouse
      model. Cytoplasmic maturation after IVM of human and mouse oocytes was assessed
      in relation to fertilization and embryonic developmental capacity. RESULTS: The
      diluted form of collagen was better for supporting the structure of the expanding
      CEOs and meiotic competence of the oocytes. Electron microscopy in combination
      with Lucifer Yellow dye coupling assay revealed that oocyte-cumulus cell
      connections could be preserved during 3D-PMC. Percentages of mouse 2-cell embryos
      after IVF were higher in the 3D-PMC group compared with in vitro controls and 2D
      PMC oocytes, but lower compared with in vivo controls. In the human model,
      percentages of polar body-extruded oocytes were significantly higher in the 3D
      PMC group compared with conventionally matured oocytes. The 3D-PMC also had a
      beneficial effect on embryonic development on Day 3 post-ICSI. CONCLUSIONS:
      Applying a 3D-PMC in the presence of a PDE3-I preserves oocyte-cumulus cell
      connections and influences oocyte developmental capacity.

PMID- 19395364
TI  - Pharmacokinetics of repeated doses of misoprostol.
AB  - BACKGROUND: Misoprostol is widely used in obstetrics and gynaecology for medical
      abortion, cervical priming and induction of labour. To aid the design of
      effective and safe regimens, we have investigated the pharmacokinetic parameters
      after the vaginal or sublingual administration of repeated doses of 400 microg of
      misoprostol. METHODS: Women undergoing termination of pregnancy by suction
      evacuation were randomized to receive 400 microg of sublingual or vaginal
      misoprostol every 3 h for five doses. Venous blood was taken at 180, 200, 240,
      360, 380, 420, 540, 560, 600, 720, 740, 780 and 900 min after the first dose of
      misoprostol for determination of the plasma level of misoprostol acid (MPA).
      RESULTS: The peak plasma levels of MPA decreased with successive doses of vaginal
      misoprostol, whereas the peak plasma levels were similar with successive doses of
      sublingual misoprostol. After the third dose, the peak plasma levels of MPA after
      sublingual misoprostol were significantly higher than those after vaginal
      administration. After the final dose, the area under the MPA concentration-time
      curve after sublingual administration was significantly higher than that after
      vaginal misoprostol (P < 0.031). However, subgroup analysis in the vaginal
      administration group showed that the progressive decline in the peak plasma
      levels of MPA occurred only in women with significant vaginal bleeding.
      CONCLUSIONS: The peak plasma level of MPA after each dose of misoprostol is
      higher and the bioavailability is also greater after sublingual administration,
      compared with that after vaginal administration, of repeated doses of
      misoprostol. The difference was probably due to the reduction in absorption of
      vaginal misoprostol in the presence of significant vaginal bleeding.

PMID- 19395365
TI  - Evaluating prediction models in reproductive medicine.
AB  - Prediction models are used in reproductive medicine to calculate the probability
      of pregnancy without treatment, as well as the probability of pregnancy after
      ovulation induction, intrauterine insemination or in vitro fertilization. The
      performance of such prediction models is often evaluated with a receiver
      operating characteristic (ROC) curve. The area under the ROC curve, also known as
      c-statistic, is then used as a measure of model performance. The value of this c
      statistic is low for most prediction models in reproductive medicine. Here, we
      demonstrate that low values of the c-statistic are to be expected in these
      prediction models, but we also show that this does not imply that these models
      are of limited use in clinical practice. The calibration of the model (the
      correspondence between model-based probabilities and observed pregnancy rates) as
      well as the availability of a clinically useful distribution of probabilities and
      the ability to correctly identify the appropriate form of management are more
      meaningful concepts for model evaluation.

PMID- 19395366
TI  - Bioethics and self-governance: the lessons of the Universal Declaration on
      Bioethics and Human Rights.
AB  - The following article analyzes the process of conception, elaboration, and
      adoption of the Universal Declaration of Bioethics and Human Rights, and reflects
      on the lessons it might hold for public bioethics on the international level. The
      author was involved in the process at a variety of levels: he provided advice to
      the IBC on behalf of the President's Council of Bioethics; he served as the U.S.
      representative to UNESCO's Intergovernmental Bioethics Committee; and led the
      U.S. Delegation in the multilateral negotiation of Government experts that
      culminated in the adoption of the declaration in its final form. The author is
      currently serving a 4-year term as a member of UNESCO's International Bioethics
      Committee.

PMID- 19395367
TI  - Normative foundations of technology transfer and transnational benefit principles
      in the UNESCO Universal Declaration on Bioethics and Human Rights.
AB  - The United Nations Scientific, Education, and Cultural Organization Universal
      Declaration on Bioethics and Human Rights (UDBHR) expresses in its title and
      substance a controversial linkage of two normative systems: international human
      rights law and bioethics. The UDBHR has the status of what is known as a
      "nonbinding" declaration under public international law. The UDBHR's foundation
      within bioethics (and association, e.g., with virtue-based or principlist
      bioethical theories) is more problematic. Nonetheless, the UDBHR contains
      socially important principles of technology transfer and transnational benefit
      (articles 14, 15, and 21). This paper is one of the first to explore how the
      disciplines of bioethics and international human rights law may interact in the
      UDBHR to advance the policy relevance and health impact of such principles. It
      investigates their normative ancestry in the UDBHR, as well as relevant
      conceptual differences between bioethics and public international law in this
      respect, and how these may be relevant to their conceptual evolution and
      application.

PMID- 19395368
TI  - A novel treatment modality in patients with premature ejaculation resistant to
      conventional methods: the neuromodulation of dorsal penile nerves by pulsed
      radiofrequency.
AB  - Premature ejaculation (PE) is the most common sexual problem experienced by men,
      and it affects 20%-30% of them. Pulsed radiofrequency (PRF) neuromodulation has
      been shown to be an effective treatment for a wide range of pain conditions. We
      used PRF to treat PE by desensitizing dorsal penile nerves in patients resistant
      to conventional treatments. Fifteen patients with a lifelong history of PE,
      defined as an intravaginal ejaculatory latency time (IELT) of <1 minute that
      occurred in more than 90% of acts of intercourse and was resistant to
      conventional treatments, were enrolled in this study. Patients with erectile
      dysfunction were excluded. The mean age of the patients was 39 +/- 9 years.
      Before and 3 weeks after the treatment, IELT and sexual satisfaction score (SSS;
      for patients and their partners) were obtained. The mean IELTs before and 3 weeks
      after procedure were 18.5 +/- 17.9 and 139.9 +/- 55.1 seconds, respectively. Side
      effects did not occur. Mean SSSs of patients before and after treatment were 1.3
      +/- 0.3 and 4.6 +/- 0.5, and mean SSSs of partners before and after treatment
      were 1.3 +/- 0.4 and 4.4 +/- 0.5, respectively. In all cases, IELT and SSS were
      significantly increased (P < .05). None of the patients or their wives reported
      any treatment failure during the follow-up period. The mean follow-up time was
      8.3 +/- 1.9 months. It is early to conclude that this new treatment modality
      might be used widely for the treatment of PE; however, because it is an
      innovative modality, placebo-controlled studies (eg, sham procedure), with larger
      numbers of patients and including assessment of penile sensitivity (eg,
      biothesiometry), are needed.

PMID- 19395369
TI  - Reliability of growth prediction with hand-wrist radiographs.
AB  - The aim of this study was to investigate the validity of hand-wrist radiographic
      analysis in estimating the amount of remaining craniofacial growth. The material
      compromised cephalograms of 22 males and 27 females with a Class I malocclusion.
      The median age of the females at the beginning (T1) was 11 years 10 months and of
      the males 12 years 6 months and at the end (T2) of treatment 14 years 7 months
      and 15 years 3 months, respectively. Statural height was measured and a lateral
      cephalogram was obtained for every patient at T1 and T2. A hand-wrist radiograph
      was taken only at T1. The cephalograms were scanned and analyzed. Relative
      dimensional growth changes in statural height as well as of the length of the
      cranial base (N-S), the maxilla (Ptm-A), and the dimensions of the mandible (Co
      Gn, Go-Gn, and Co-Gn) from T1 to T2 were determined and statistically compared
      (Pearson's correlation coefficients) with the growth prediction assessed with the
      help of hand-wrist radiographs according to Greulich and Pyle. The results showed
      a highly significant correlation between statural growth increases and growth
      prediction assessed from the hand-wrist radiographs (females: r = 0.68; males: r
      = 0.7). Concerning craniofacial structures, the increase in mandibular corpus
      showed the highest correlation with growth prediction (females: r = 0.21; males:
      r = 0.52), but this association would not allow a reliable growth prediction.
      There was no significant correlation between growth increases of the cranial
      base, the maxilla, the ramus, and the effective length of the mandible and growth
      prediction assessed with the help of hand-wrist radiographs. As each patient has
      an individual growth pattern and different craniofacial structures show
      individual growth potential, it is questionable if quantitative craniofacial
      growth prediction with the help of hand-wrist radiographs is reliable. However,
      in an individual case for the assessment of the timing of the growth process, a
      hand-wrist radiograph can contribute to treatment planning.

PMID- 19395370
TI  - Is bodily advancement of the lower incisors possible?
AB  - Some Class II malocclusions are due, at least in part, to a retruded lower dental
      arch relative to the mandibular body. The purpose of this study was to determine
      if a direct anterior force on the lower incisors could lead to bodily movement of
      these teeth. Twenty-seven patients (9 males, 18 females; mean age: 9.8 years)
      were treated with a reverse headgear (RHG) in the lower dental arch combined with
      labial root torque of the lower incisors. An activator was added to disclude the
      arches. This group was compared with 26 patients (10 males, 16 females; mean age:
      9.7 years) treated with an activator combined with conventional posterior
      extraoral traction on the upper molars. All patients had a second stage of
      treatment with fixed appliances and Class II elastic wear. At the end of
      treatment, all patients had a Class I relationship and a normal overjet. Lateral
      cephalograms were taken before (T1), after the first stage (T2), and at the end
      of active (T3) treatment. Independent sample t-tests were used to assess the
      differences between the two groups of patients. In the RHG group, despite the
      applied root torque, the lower incisors showed anterior crown tipping. Labial
      root displacement was not observed. At T2, this labial tipping partially
      relapsed. Furthermore, the use of RHG appeared to decrease bone apposition in the
      anterior part of the symphysis, leading to a reduction in width. Bodily
      advancement of the lower incisors was not achieved with the application of labial
      root torque and anteriorly directed force on the mandibular arch. The width limit
      of the lower anterior apical base should be respected during orthodontic
      treatment planning.

PMID- 19395371
TI  - Orthodontists' and laypersons' aesthetic assessment of Class III subjects
      referred for orthognathic surgery.
AB  - This study was undertaken to compare laypersons' and professionals' perception of
      soft tissue profiles of Class III adults, and to evaluate which cephalometric
      variables are likely to influence the profile assessment score (PAS). Lateral
      headfilms and coloured profile photographs of 18 skeletal Class III Caucasian
      adult patients (10 males, 8 females with a mean age of 24.5 years) prior to
      surgery, and nine adult Caucasian patients (four males, five females with a mean
      age of 27.4 years) with a dental Class I occlusion and no major skeletal
      discrepancy were included in the study. The headfilms were hand traced and
      digitized. Various cephalometric variables were calculated by computer software.
      Each printed profile photograph was evaluated aesthetically by 18 laypersons and
      18 orthodontists using a 10-graded visual analogue scale (VAS) and a standard
      profile for calibration. Intra-observer reliability was tested and no significant
      error was found. Paired and unpaired t-tests were used to compare the scores. The
      association between various cephalometric variables and the PAS was tested. In
      general, compared with orthodontists, laypersons were less critical in their
      evaluation of the Class III profiles (+0.3 grade on the VAS) as well as the
      reference profiles (+0.7). The reference profiles were found to be more
      attractive than the Class III profiles by both laypersons and orthodontists (+2.3
      grades). The degree of facial concavity had a negatively predictive value for the
      orthodontists' and laypersons' evaluations. The degree of facial concavity
      together with the steepness of the mandibular plane were negatively predictive
      factors for the PAS given by the orthodontists.

PMID- 19395372
TI  - Comparative efficiency of Class II malocclusion treatment with the pendulum
      appliance or two maxillary premolar extractions and edgewise appliances
      [corrected].
AB  - The objective of this study was to compare, on study models and initial
      cephalograms, the efficiency of Class II malocclusion treatment with the pendulum
      appliance, and with two maxillary premolar extraction protocol. The sample
      consisted of 48 treated Class II malocclusion patients: group 1 comprised 22
      patients (7 males, 15 females) treated with the pendulum appliance, with an
      initial mean age of 14.44 years and group 2, 26 patients (14 males, 12 females)
      treated with two maxillary premolar extractions at an initial mean age of 13.66
      years. To compare the efficiency of each treatment protocol, the occlusal
      outcomes were evaluated on dental casts using the Peer Assessment Rating (PAR)
      Index and the treatment time (TT) of each group was calculated on clinical
      charts. The degree of treatment efficiency was calculated as the ratio between
      the percentage of occlusal improvement, evaluated through the PAR index, and TT.
      Statistical analysis was undertaken by means of t-tests. The findings
      demonstrated that the two maxillary premolar extraction protocol provided the
      occlusal outcomes in a shorter time (group 1: 45.7 months, group 2: 23.01 months)
      and, therefore, demonstrated greater treatment efficiency than the pendulum
      appliance.

PMID- 19395373
TI  - Mammalian nitrilase 1 homologue Nit1 is a negative regulator in T cells.
AB  - The mammalian Nit1 protein is homologous to plant and bacterial nitrilases. In
      flies and worms, Nit1 is fused to the 5' end of Fhit, suggesting that Nit1 may
      functionally interact with the Fhit pathway. Fhit has been shown to play a role
      of a tumor suppressor. Somatic loss of Fhit in human tissues is associated with a
      wide variety of cancers. Deletion of Fhit results in a predisposition to induced
      and spontaneous tumors in mice. It has been suggested that Nit1 collaborates with
      Fhit in tumor suppression. Similar to mice lacking Fhit, Nit1-deficient mice are
      more sensitive to carcinogen-induced tumors. It was previously shown that ectopic
      expression of Nit1 or Fhit led to caspase activation and apoptosis, and that both
      proteins may play a role in DNA damage-induced apoptosis. In this study, we
      analyzed the physiological function of Nit1 in T cells using Nit1-knockout mice.
      Nit1-deficient T cells can undergo apoptosis induced by DNA damage due to
      irradiation and chemical treatment. However, apoptosis induced by Fas or Ca(++)
      signals appeared to be compromised. Additionally, Nit1 deficiency resulted in T
      cell hyperproliferative responses induced by TCR stimulation. The expressions of
      T cell activation markers were elevated in Nit1(-/-) T cells. There was a
      spontaneous cell cycle entry and enhanced cell cycle progression in Nit1(-/-) T
      cells. These data indicate that Nit1 is a novel negative regulator in primary T
      cells.

PMID- 19395374
TI  - Irradiated CIITA-positive mammary adenocarcinoma cells act as a potent anti-tumor
      preventive vaccine by inducing tumor-specific CD4+ T cell priming and CD8+ T cell
      effector functions.
AB  - In the present study, we investigated the possibility to use irradiated, non
      replicating class II transcriptional activator (CIITA)-transfected tumor TS/A
      cells as a cell-based vaccine. Eighty-three percent of TS/A-CIITA-vaccinated mice
      were completely protected from tumor growth and the remaining 17% displayed
      significant reduction of tumor growth. In contrast, only 30% of mice injected
      with irradiated TS/A parental cells were protected from tumor growth, whereas the
      remaining 70% of animals remained unprotected. Immunity generated in the TS/A
      CIITA-vaccinated mice correlated with an efficient priming of CD4(+) T cells and
      consequent triggering and maintenance of CD8(+) CTL effectors, as assessed by
      adoptive transfer assays. Important qualitative differences were observed between
      the two cell-based vaccines, as TS/A-CIITA-vaccinated mice developed a CTL
      response containing a large proportion of anti-gp70 AH1 epitope-specific cells,
      completely absent in TS/A-vaccinated mice, and a mixed T(h)1/T(h)2 type of
      response as opposed to a T(h)2 type of response in TS/A-vaccinated mice. Finally,
      in TS/A-CIITA-vaccinated mice, a statistically significant reduction in the
      percentage and absolute number of CD4(+) CD25(+) T regulatory cells as compared
      with those of untreated mice with growing tumors (P < 0.001) or mice vaccinated
      with TS/A parental cells were observed. These results let to envisage the use of
      CIITA-transfected non-replicating tumor cells as a vaccination strategy for
      prevention and, possibly, adjuvant immunotherapy in human settings.

PMID- 19395375
TI  - Expression of survivin in lung eosinophils is associated with pathology in a
      mouse model of allergic asthma.
AB  - Humans vary markedly in their propensity to develop asthma, despite often being
      exposed to similar environmental stimuli. Similarly, mouse strains vary in
      susceptibility to airways pathology in experimental asthma. Sensitization and
      aerosol challenge with ovalbumin (OVA) induces eosinophil accumulation, mucus
      production and airways obstruction in BALB/c and C57BL/6 mice. In contrast,
      CBA/Ca mice show relatively little pathology. Allergen-induced production of IL
      4, IL-5, IL-10 and IFN-gamma was detected in all three strains, with BALB/c mice
      generating the highest levels of IL-4, IL-5 and IL-10. Microarray analysis was
      used to identify genes differentially regulated in lung tissue after OVA
      challenge. Differentially regulated genes in the lungs of the asthma-susceptible
      C57BL/6 and BALB/c strains numbered 242 and 145, respectively, whereas only 42
      genes were differentially expressed in the resistant CBA/Ca strain. In C57BL/6
      mice, transcripts were enriched for adhesion molecules and this was associated
      with high levels of eosinophil recruitment. Differentially regulated genes in the
      lungs of only the asthma-susceptible strains numbered 64 and several of these
      have not previously been associated with asthma. Many of the genes differentially
      regulated in the susceptible strains were enzymes involved in inflammation. Using
      network analysis, mRNA for the anti-apoptotic protein survivin was found to be up
      regulated in the lungs following allergen challenge. Survivin mRNA and protein
      were also expressed at high levels in eosinophils recovered by bronchoalveolar
      lavage from BALB/c and C57BL/6 mice. We propose that rapid apoptosis of lung
      eosinophils due to low expression of survivin contributes to the limitation of
      pathology in CBA/Ca mice.

PMID- 19395376
TI  - Transmembrane signaling in the maltose ABC transporter MalFGK2-E: periplasmic
      MalF-P2 loop communicates substrate availability to the ATP-bound MalK dimer.
AB  - ABC transporters are ubiquitous membrane proteins that translocate solutes across
      biological membranes at the expense of ATP. In prokaryotic ABC importers, the
      extracytoplasmic anchoring of the substrate-binding protein (receptor) is
      emerging as a key determinant for the structural rearrangements in the
      cytoplasmically exposed ATP-binding cassette domains and in the transmembrane
      gates during the nucleotide cycle. Here the molecular mechanism of such signaling
      events was addressed by electron paramagnetic resonance spectroscopy of spin
      labeled ATP-binding cassette maltose transporter variants (MalFGK2-E). A series
      of doubly spin-labeled mutants in the MalF-P2 domain involving positions 92, 205,
      239, 252, and 273 and one triple mutant labeled at positions 205/252 in P2 and 83
      in the Q-loop of MalK were assayed. The EPR data revealed that the substrate
      binding protein MalE is bound to the transporter throughout the transport cycle.
      Concomitantly with the three conformations of the ATP-binding cassette MalK2,
      three functionally relevant conformations are found also in the periplasmic MalF
      P2 loop, strictly dependent on cytoplasmic nucleotide binding and periplasmic
      docking of liganded MalE to MalFG. The reciprocal communication across the
      membrane unveiled here gives first insights into the stimulatory effect of MalE
      on the ATPase activity, and it is suggested to be an important mechanistic
      feature of receptor-coupled ABC transporters.

PMID- 19395377
TI  - Inter-alpha-trypsin inhibitor promotes bronchial epithelial repair after injury
      through vitronectin binding.
AB  - Pulmonary epithelial injury is central to the pathogenesis of many lung diseases,
      such as asthma, pulmonary fibrosis, and the acute respiratory distress syndrome.
      Regulated epithelial repair is crucial for lung homeostasis and prevents scar
      formation and inflammation that accompany dysregulated healing. The extracellular
      matrix (ECM) plays an important role in epithelial repair after injury.
      Vitronectin is a major ECM component that promotes epithelial repair. However,
      the factors that modify cell-vitronectin interactions after injury and help
      promote epithelial repair are not well studied. Inter-alpha-trypsin inhibitor
      (IaI) is an abundant serum protein. IaI heavy chains contain von Willebrand A
      domains that can bind the arginine-glycine-aspartate domain of vitronectin. We
      therefore hypothesized that IaI can bind vitronectin and promote vitronectin
      induced epithelial repair after injury. We show that IaI binds vitronectin at the
      arginine-glycine-aspartate site, thereby promoting epithelial adhesion and
      migration in vitro. Furthermore, we show that IaI-deficient mice have a
      dysregulated response to epithelial injury in vivo, consisting of decreased
      proliferation and epithelial metaplasia. We conclude that IaI interacts not only
      with hyaluronan, as previously reported, but also other ECM components like
      vitronectin and is an important regulator of cellular repair after injury.

PMID- 19395378
TI  - Loss of Wip1 sensitizes cells to stress- and DNA damage-induced apoptosis.
AB  - In response to various environmental stresses, the stress-responsive MAPKs p38
      and JNK are activated and phosphorylate ATF2 and c-Jun transcription factors,
      thereby affecting cell-fate decision. Targeted gene disruption studies have
      established that JNK-c-Jun signaling plays a vital role in stress-induced
      apoptosis. The oncogenic phosphatase Wip1 acts as an important regulator in DNA
      damage pathway by dephosphorylating a spectrum of proteins including p53, p38,
      Chk1, Chk2, and ATM. In this study we show that Wip1 negatively regulates the
      activation of MKK4-JNK-c-Jun signaling during stress-induced apoptosis. The loss
      of Wip1 function sensitizes mouse embryonic fibroblasts to stress-induced
      apoptosis via the activation of both p38-ATF2 and JNK-c-Jun signaling. Here we
      reveal that Wip1 has dual roles in alternatively regulating stress- and DNA
      damage-induced apoptosis through p38/JNK MAPKs and p38/p53-dependent pathways,
      respectively. Our results point to Wip1 as a general regulator of apoptosis,
      which further supports its role in tumorigenesis.

PMID- 19395379
TI  - Novel interactions of glycosaminoglycans and bacterial glycolipids mediate
      binding of enterococci to human cells.
AB  - Enterococcus faecalis is among the most important nosocomial pathogens. The
      intestinal mucosa is considered to be the main site used by these bacteria for
      entrance and dissemination. A better understanding of the mechanisms involved in
      colonization and invasion of enterococci may help to devise methods to prevent
      infections in hospitalized patients. Glycosaminoglycans, which are present on the
      surface of all eukaryotic cells, were investigated with regard to their role as
      host receptors for adhesion of E. faecalis. Competitive binding assays, enzymatic
      digestion, and reduction of the sulfation of the glycosaminoglycan chains
      indicated that heparin and heparan sulfate, but not chondroitin sulfate B, played
      important roles in adhesion of E. faecalis 12030 to Caco2 cells. By using
      proteinases and carbohydrate oxidation by sodium meta-periodate to modify the
      bacterial surface, it could be demonstrated that a sugar-containing molecule
      rather than a protein is the bacterial ligand mediating adhesion to eukaryotic
      cells. Preincubation of Caco2 cells with the enterococcal glycolipid
      diglucosyldiacylglycerol but not other carbohydrate cell wall components
      inhibited bacterial binding. These results may indicate that heparin and/or
      heparan sulfate on host epithelial cells and diglucosyldiacylglycerol, either
      itself or as a partial structure of lipoteichoic acid, are involved in
      enterococcal adhesion to colonic epithelia, the first step in translocation from
      the intestinal tract.

PMID- 19395380
TI  - Zinc ion-induced domain organization in metallo-beta-lactamases: a flexible "zinc
      arm" for rapid metal ion transfer?
AB  - The reversible unfolding of metallo-beta-lactamase from Chryseobacterium
      meningosepticum (BlaB) by guanidinium hydrochloride is best described by a three
      state model including folded, intermediate, and unfolded states. The
      transformation of the folded apoenzyme into the intermediate state requires only
      very low denaturant concentrations, in contrast to the Zn2-enzyme. Similarly,
      circular dichroism spectra of both BlaB and metallo-beta-lactamase from Bacillus
      cereus 569/H/9 (BcII) display distinct differences between metal-free and Zn2
      enzymes, indicating that the zinc ions affect the folding of the proteins, giving
      a larger alpha-helix content. To identify the regions of the protein involved in
      this zinc ion-induced change, a hydrogen deuterium exchange study with matrix
      assisted laser desorption ionization tandem time of flight mass spectrometry on
      metal-free and Zn1- and Zn2-BcII was carried out. The region spanning the metal
      binding metallo-beta-lactamases (MBL) superfamily consensus sequence His-X-His-X
      Asp motif and the loop connecting the N- and C-terminal domains of the protein
      undergoes a zinc ion-dependent structural change between intrinsically disordered
      and ordered states. The inherent flexibility even appears to allow for the
      formation of metal ion-bridged protein-protein complexes which may account for
      both electrospray ionization-mass spectroscopy results obtained upon variation of
      the zinc/protein ratio and stoichiometry-dependent variations of 199mHg-perturbed
      angular correlation of gamma-rays spectroscopic data. We suggest that this
      flexible "zinc arm" motif, present in all the MBL subclasses, is disordered in
      metal-free MBLs and may be involved in metal ion acquisition from zinc-carrying
      molecules different from MBL in an "activation on demand" regulation of enzyme
      activity.

PMID- 19395381
TI  - Dual nuclease and helicase activities of Helicobacter pylori AddAB are required
      for DNA repair, recombination, and mouse infectivity.
AB  - Helicobacter pylori infection of the human stomach is associated with disease
      causing inflammation that elicits DNA damage in both bacterial and host cells.
      Bacteria must repair their DNA to persist. The H. pylori AddAB helicase
      exonuclease is required for DNA repair and efficient stomach colonization. To
      dissect the role of each activity in DNA repair and infectivity, we altered the
      AddA and AddB nuclease (NUC) domains and the AddA helicase (HEL) domain by site
      directed mutagenesis. Extracts of Escherichia coli expressing H. pylori
      addA(NUC)B or addAB(NUC) mutants unwound DNA but had approximately half of the
      exonuclease activity of wild-type AddAB; the addA(NUC)B(NUC) double mutant lacked
      detectable nuclease activity but retained helicase activity. Extracts with
      AddA(HEL)B lacked detectable helicase and nuclease activity. H. pylori with the
      single nuclease domain mutations were somewhat less sensitive to the DNA-damaging
      agent ciprofloxacin than the corresponding deletion mutant, suggesting that
      residual nuclease activity promotes limited DNA repair. The addA(NUC) and
      addA(HEL) mutants colonized the stomach less efficiently than the wild type;
      addB(NUC) showed partial attenuation. E. coli DeltarecBCD expressing H. pylori
      addAB was recombination-deficient unless H. pylori recA was also expressed,
      suggesting a species-specific interaction between AddAB and RecA and also that H.
      pylori AddAB participates in both DNA repair and recombination. These results
      support a role for both the AddAB nuclease and helicase in DNA repair and
      promoting infectivity.

PMID- 19395383
TI  - Psalmotoxin-1 docking to human acid-sensing ion channel-1.
AB  - Acid-sensing ion channel-1 (ASIC-1) is a proton-gated ion channel implicated in
      nociception and neuronal death during ischemia. Recently the first crystal
      structure of a chicken ASIC was obtained. Expanding upon this work, homology
      models of the human ASICs were constructed and evaluated. Energy-minimized
      structures were tested for validity by in silico docking of the models to
      psalmotoxin-1, which potently inhibits ASIC-1 and not other members of the
      family. The data are consistent with prior radioligand binding and functional
      assays while also explaining the selectivity of PcTX-1 for homomeric hASIC-1a.
      Binding energy calculations suggest that the toxin and channel create a complex
      that is more stable than the channel alone. The binding is dominated by the
      coulombic contributions, which account for why the toxin-channel interaction is
      not observed at low pH. The computational data were experimentally verified with
      single channel and whole-cell electrophysiological studies. These validated
      models should allow for the rational design of specific and potent peptidomimetic
      compounds that may be useful for the treatment of pain or ischemic stroke.

PMID- 19395382
TI  - Determinants of histone H4 N-terminal domain function during nucleosomal array
      oligomerization: roles of amino acid sequence, domain length, and charge density.
AB  - Mg(2+)-dependent oligomerization of nucleosomal arrays is correlated with higher
      order folding transitions that stabilize chromosome structure beyond the 30-nm
      diameter fiber. In the present studies, we have employed a novel mutagenesis
      based approach to identify the macromolecular determinants that control H4 N
      terminal domain (NTD) function during oligomerization. Core histones were
      engineered in which 1) the H2A, H2B, and H3 NTDs were swapped onto the H4 histone
      fold; 2) the length of the H4 NTD and the H2A NTD on the H4 histone fold, were
      increased; 3) the charge density of the NTDs on the H4 histone fold was increased
      or decreased; and 4) the H4 NTD was placed on the H2B histone fold. Model
      nucleosomal arrays were assembled from wild type and mutant core histone
      octamers, and Mg(2+)-dependent oligomerization was characterized. The results
      demonstrated that the H2B and H3 NTDs could replace the H4 NTD, as could the H2A
      NTD if it was duplicated to the length of the native H4 NTD. Arrays oligomerized
      at lower salt concentrations as the length of the NTD on the H4 histone fold was
      increased. Mutations that decreased the NTD charge density required more Mg(2+)
      to oligomerize, whereas mutants that increased the charge density required less
      salt. Finally, the H4 NTD functioned differently when attached to the H2B histone
      fold than the H4 histone fold. These studies have revealed new insights into the
      biochemical basis for H4 NTD effects on genome architecture as well as the
      protein chemistry that underlies the function of the intrinsically disordered H4
      NTD.

PMID- 19395386
TI  - Differentially expressed membrane transporters in rice roots may contribute to
      cultivar dependent salt tolerance.
AB  - Salinity tolerance in rice, like in other glycophytes, is a function of cellular
      ion homeostasis. The large divergence in ion homeostasis between the salt
      tolerant FL478 and salt-sensitive IR29 rice varieties can be exploited to
      understand mechanisms of salinity tolerance. Physiological studies indicate that
      FL478 shows a lower Na(+) influx, a reduced Na(+) translocation to the shoot, and
      maintains a lower Na(+):K(+) ratio. To understand the basis of these differences,
      a comparative investigation of transcript regulation in roots of the two
      cultivars was undertaken. This analysis revealed that genes encoding aquaporins,
      a silicon transporter, and N transporters are induced in both cultivars. However,
      transcripts for cation transport proteins including OsCHX11, OsCNGC1, OsCAX, and
      OsTPC1 showed differential regulation between the cultivars. The encoded proteins
      are likely to participate in reducing Na(+) influx, lowering the tissue
      Na(+):K(+) ratio and limiting the apoplastic bypass flow in roots of FL478 and
      are therefore important new targets to improve salt tolerance in rice.

PMID- 19395387
TI  - Light-saturated photosynthetic rate in high-nitrogen rice (Oryza sativa L.)
      leaves is related to chloroplastic CO2 concentration.
AB  - To identify the effect of nitrogen (N) nutrition on photosynthetic efficiency and
      mesophyll conductance of rice seedlings (Oryza sativa L., cv. 'Shanyou 63' hybrid
      indica China), hydroponic experiments with different concentrations of N were
      conducted in a greenhouse. Although leaf N concentration on a dry mass basis
      increased with increasing supply of N, no significant differences in seedling
      biomass were observed. A higher light-saturated CO(2) assimilation rate (A) with
      a high concentration of supplied N was associated with a higher carboxylation
      efficiency (CE), but not a higher apparent quantum yield (alpha). Based on
      classic photosynthetic models, both the Rubisco content and the ribulose
      bisphosphate (RuBP) regeneration rate were sufficient for light-saturated
      photosynthesis in rice seedlings; the estimated chloroplastic CO(2) concentration
      (C(c)) and mesophyll conductance (g(m)) demonstrated that a low C(c) was the
      ultimate limiting factor to photosynthetic efficiency with a higher N supply. Due
      to a greater chloroplast size (i.e. a shorter distance to the plasma membrane)
      with a higher supply of N, the CO(2) transport resistance in the liquid phase
      (g(liq)) in high-N leaves was lower than that in low-N leaves, which resulted in
      higher g(m) and C(c) in high-N leaves. Although CE(A/Ci) was higher with a high
      supply of N, there were no differences in CE(A/Cc) between plants grown with
      different concentrations of N, indicating that the carboxylation capacity of
      Rubisco between plants grown at different N concentrations was constant. The
      enhanced photosynthetic rate with supply of a high N concentration was attributed
      to a higher CO(2) concentration in the chloroplasts, related to a higher
      mesophyll conductance due to an increased chloroplast size.

PMID- 19395388
TI  - The impact of blue light on leaf mesophyll conductance.
AB  - Blue light has many direct and indirect effects on photosynthesis. The impact of
      blue light on mesophyll conductance (g(m)), one of the main diffusive limitation
      to photosynthesis, was investigated in leaves of Nicotiana tabacum and Platanus
      orientalis, characterized by high and low g(m), respectively. Leaves were exposed
      to blue light fractions between 0% and 80% of incident light intensity (300
      micromol photons m(-2) s(-1)), the other fraction being supplied as red light.
      Leaves exposed to blue light showed reduced photosynthesis and unaltered stomatal
      conductance. The g(m), measured using the chlorophyll fluorescence-based method,
      was strongly reduced in both plant species. Such a reduction of g(m) may not be
      real, as several assumptions used for the calculation of g(m) by fluorescence may
      not hold under blue light. To assess possible artefacts, the electron transport
      rate measured by fluorescence (J(f)) and by gas-exchange (J(c)) were compared in
      leaves exposed to different fractions of blue light under non-photorespiratory
      conditions. The two values were only equal, a prerequisite for correct g(m)
      measurements, when the illumination was totally provided as red light. Under
      increasing blue light levels an increasing discrepancy was observed, which
      suggests that J(f) was not correctly calculated, and that such an error could
      also upset g(m) measurements. Blue light was not found to change the absorbance
      of light by leaves, whereas it slightly decreased the distribution of light to
      PSII. To equate J(f) and J(c) under blue light, a further factor must be added to
      the J(f) equation, which possibly accounted for the reduced efficiency of energy
      transfer between the pigments predominantly absorbing blue light (the
      carotenoids) and the chlorophylls. This correction reduced by about 50% the
      effect of blue light on g(m). However, the residual reduction of g(m) under blue
      light was real and significant, although it did not appear to limit the
      chloroplast CO(2) concentration and, consequently, photosynthesis. Reduction of
      g(m) might be caused by chloroplast movement to avoid photodamage, in turn
      affecting the chloroplast surface exposed to intercellular spaces. However, g(m)
      reduction occurred immediately after exposure to blue light and was complete
      after less than 3 min, whereas chloroplast relocation was expected to occur more
      slowly. In addition, fast g(m) reduction was also observed after inhibiting
      chloroplast movement by cytochalasin. It is therefore concluded that g(m)
      reduction under blue light is unlikely to be caused by chloroplast movement only,
      and must be elicited by other, as yet unknown, factors.

PMID- 19395389
TI  - Analysing nitrogen responses of cereals to prioritize routes to the improvement
      of nitrogen use efficiency.
AB  - The efficient use of fertilizer nitrogen (N) is crucial to sustainable human
      nutrition. All crops receive significant amounts of additional N in temperate
      environments, through fixation or fertilizer use. This paper reviews progress
      towards the efficient use of fertilizer N by winter wheat (Triticum aesitivum L.)
      and spring barley (Hordeum vulgare L.) in the UK, acknowledging that on-farm this
      is governed by economics. Recent multi-site N response experiments on old and
      modern varieties show that yield improvements since the 1980s have been
      accompanied by increases in economic optimum N amounts for wheat but not for
      spring barley. On-farm N use efficiency (NUE) has increased for barley because
      increased yields with optimum N were associated with compensatory decreases in
      grain N concentration, whereas on-farm NUE has not increased for wheat because
      grain N concentration has not changed and improvements in N capture were
      insufficient to make up for the increased yield. Genetic effects on NUE are shown
      to differ markedly depending on whether they are determined at a single N rate,
      as in variety trials, or with optimum N amounts. It is suggested that, in order
      to elicit faster improvement in NUE on farms, breeding and variety testing should
      be conducted at some sites with more than one level of applied N, and that grain
      N%, N harvest index, and perhaps canopy N ratio (kg N ha(-1) green area) should
      be measured more widely. It is also suggested that, instead of using empirical
      functions, N responses might be analysed more effectively using functions based
      on explanations of yield determination for which the parameters have some
      physiological meaning.

PMID- 19395390
TI  - Resistances along the CO2 diffusion pathway inside leaves.
AB  - CO(2) faces a series of resistances while diffusing between the substomatal
      cavities and the sites of carboxylation within chloroplasts. The absence of
      techniques to measure the resistance of individual steps makes it difficult to
      define their relative importance. Resistance to diffusion through intercellular
      airspace differs between leaves, but is usually of minor importance. Leaves with
      high photosynthetic capacity per unit leaf area reduce mesophyll resistance by
      increasing the surface area of chloroplasts exposed to intercellular airspace per
      unit leaf area, S(c). Cell walls impose a significant resistance. Assuming an
      effective porosity of the cell wall of 0.1 or 0.05, then cell walls could account
      for 25% or 50% of the total mesophyll resistance, respectively. Since the
      fraction of apoplastic water that is unbound and available for unhindered CO(2)
      diffusion is unknown, it is possible that the effective porosity is <0.05.
      Effective porosity could also vary in response to changes in pH or cation
      concentration. Consequently, cell walls could account for >50% of the total
      resistance and a variable proportion. Most of the remaining resistance is imposed
      by one or more of the three membranes as mesophyll resistance can be altered by
      varying the expression of cooporins. The CO(2) permeability of vesicles prepared
      from chloroplast envelopes has been reduced by RNA interference (RNAi) expression
      of NtAQP1, but not those prepared from the plasma membrane. Carbonic anhydrase
      activity also influences mesophyll resistance. Mesophyll resistance is relatively
      insensitive to the manipulation of any step in the pathway because it represents
      only part of the total and may also be countered by pleiotropic compensatory
      changes. The parameters in greatest need of additional measurements are S(c),
      mesophyll cell wall thickness, and the permeabilities of the plasma membrane and
      chloroplast envelope.

PMID- 19395391
TI  - Role of mesophyll diffusion conductance in constraining potential photosynthetic
      productivity in the field.
AB  - Limited mesophyll diffusion conductance to CO(2) (g(m)) can significantly
      constrain plant photosynthesis, but the extent of g(m)-limitation is still
      imperfectly known. As g(m) scales positively with foliage photosynthetic capacity
      (A), the CO(2) drawdown from substomatal cavities (C(i)) to chloroplasts (C(C),
      C(i)-C(C)=A/g(m)) rather than g(m) alone characterizes the mesophyll diffusion
      limitations of photosynthesis. The dependencies of g(m) on A, foliage structure
      (leaf dry mass per unit area, M(A)), and the resulting drawdowns across a dataset
      of 81 species of contrasting foliage structure and photosynthetic potentials
      measured under non-stressed conditions were analysed to describe the structure
      driven potential photosynthetic limitations due to g(m). Further the effects of
      key environmental stress factors and leaf and plant developmental alterations on
      g(m) and CO(2) drawdown were evaluated and the implications of varying g(m) on
      foliage photosynthesis in the field were simulated. The meta-analysis
      demonstrated that g(m) of non-stressed leaves was negatively correlated with
      M(A), and despite the positive relationship between g(m) and A, the CO(2)
      drawdown was larger in leaves with more robust structure. The correlations were
      stronger with mass-based g(m) and A, probably reflecting the circumstance that
      mesophyll diffusion is a complex three-dimensional process that scales better
      with mesophyll volume-weighted than with leaf area-weighted traits. The analysis
      of key environmental stress effects on g(m) and CO(2) drawdowns demonstrated that
      the effect of individual stresses on CO(2) drawdowns varies depending on the
      stress effects on foliage structure and assimilation rates. Leaf diffusion
      limitations are larger in non-senescent older leaves and also in senescent
      leaves, again reflecting more robust leaf structure and/or non-co-ordinated
      alterations in leaf photosynthesis and g(m). According to simulation analyses, in
      plants with a larger part of the overall diffusion conductance from the ambient
      atmosphere to the chloroplasts in the mesophyll, photosynthesis is less sensitive
      to changes in stomatal conductance. Accordingly, in harsher environments that
      support vegetation with tougher long-living stress-tolerant leaves with lower
      g(m), reductions in stomatal conductance that are common during stress periods
      are expected to alter photosynthesis less than in species where a larger part of
      the total diffusion limitation is determined by stomata. While structural
      robustness improves plant performance under environmental stress, low g(m) and
      inherently large CO(2) drawdown in robust leaves limits the photosynthesis of
      these plants more severely under favourable conditions when stomatal conductance
      is high. The differences in overall responsiveness to environmental modifications
      of plants with varying g(m) need consideration in current large-scale ecosystem
      productivity models.

PMID- 19395392
TI  - Exploiting the potential of plants with crassulacean acid metabolism for
      bioenergy production on marginal lands.
AB  - Crassulacean acid metabolism (CAM) is a photosynthetic adaptation that
      facilitates the uptake of CO(2) at night and thereby optimizes the water-use
      efficiency of carbon assimilation in plants growing in arid habitats. A number of
      CAM species have been exploited agronomically in marginal habitats, displaying
      annual above-ground productivities comparable with those of the most water-use
      efficient C(3) or C(4) crops but with only 20% of the water required for
      cultivation. Such attributes highlight the potential of CAM plants for carbon
      sequestration and as feed stocks for bioenergy production on marginal and
      degraded lands. This review highlights the metabolic and morphological features
      of CAM that contribute towards high biomass production in water-limited
      environments. The temporal separation of carboxylation processes that underpins
      CAM provides flexibility for modulating carbon gain over the day and night, and
      poses fundamental questions in terms of circadian control of metabolism, growth,
      and productivity. The advantages conferred by a high water-storage capacitance,
      which translate into an ability to buffer fluctuations in environmental water
      availability, must be traded against diffusive (stomatal plus internal)
      constraints imposed by succulent CAM tissues on CO(2) supply to the cellular
      sites of carbon assimilation. The practicalities for maximizing CAM biomass and
      carbon sequestration need to be informed by underlying molecular, physiological,
      and ecological processes. Recent progress in developing genetic models for CAM
      are outlined and discussed in light of the need to achieve a systems-level
      understanding that spans the molecular controls over the pathway through to the
      agronomic performance of CAM and provision of ecosystem services on marginal
      lands.

PMID- 19395393
TI  - Changes in care and outcome of very preterm babies in the Parisian region between
      1998 and 2003.
AB  - OBJECTIVE: To assess evolution in the care and health of very preterm babies
      between 1998 and 2003 after implementation of a regionalisation policy in France.
      DESIGN: Comparison of two population-based cohorts. SETTING: The Parisian region.
      PATIENTS: All live births at 24-31 weeks of gestation in 1997 (EPIPAGE study,
      n=488) and in 2003 (MOSAIC study, n=580). Interventions Implementation of
      regionalised perinatal networks. Main outcome measures In-hospital mortality and
      morbidity, including intraventricular haemorrhage (IVH) grade III and IV, cystic
      periventricular leucomalacia (PVL) and bronchopulmonary dysplasia (BPD). RESULTS:
      Over this period, babies born in level III units rose from 67% to 77% and use of
      antenatal corticosteroids, indicated deliveries and surfactant increased. In
      hospital mortality and IVH grades III/IV declined, ORs of 0.66 (95% CI 0.46 to
      0.95) and 0.27 (95% CI 0.15 to 0.47), respectively, while PVL and BPD stayed
      constant. The rate of very preterm babies discharged alive per 1000 total births
      increased by 18%, but declined for babies with severe brain lesions. CONCLUSIONS:
      The authors found improvements in mortality and morbidity for very preterm babies
      and changes in their care over a 6-year period following reinforcement of
      regionalisation policies.

PMID- 19395394
TI  - Short-term outcomes following intrauterine transfusion in Scotland.
AB  - AIM: To describe neonatal outcomes following intrauterine transfusion (IUT) for
      severe Rhesus isoimmunisation from 1993 to 2004. RESULTS: 116 neonates who had
      undergone 457 IUTs (median 4, range 1-9) were identified. Three neonates died,
      all before 1995 (two because of hypoxic ischaemic multiorgan failure and one
      because of overwhelming Escherichia coli sepsis). 13 neonates (11%) were
      delivered by emergency Caesarean section following either IUT complication or
      spontaneous onset of preterm labour. They were more likely to require intubation
      (p<0.0001), on-going respiratory support (p=0.0007) and an exchange transfusion
      (p=0.007). 23 (20%) required an exchange transfusion and 63 (54%) at least one
      top-up transfusion. CONCLUSIONS: Management of severe Rhesus disease is
      associated with encouraging neonatal outcomes and most infants can be managed
      with phototherapy and a few top-up transfusions. IUT complications are rare but
      significantly increase neonatal mortality and morbidity. Antenatal counselling
      should address the likely postnatal course for these infants.

PMID- 19395395
TI  - Meconium-stained amniotic fluid: discharge vigorous newborns.
AB  - BACKGROUND: Most infants born through meconium-stained amniotic fluid (MSAF) are
      observed clinically for 24 h postnatally. Only 5% of infants born through MSAF
      develop the meconium aspiration syndrome (MAS), a serious condition requiring
      medical intervention. OBJECTIVE: To evaluate the value of 24-h postnatal
      observation of infants born through MSAF. METHODS: A cohort of 394 term neonates
      born through MSAF was studied. Data were collected on Apgar scores, the
      development of MAS and other perinatal factors. RESULTS: Nineteen of the 394
      (4.8%) infants born through MSAF developed MAS. 298 (76%) infants had a 5-minute
      Apgar score (5'AS) of >or=9. In this group the number of infants developing MAS
      (1; 0.3%) was significantly lower compared with the 5'AS <or=8 group (18; 19%).
      CONCLUSION: MAS develops rarely in infants born through MSAF with 5'AS above 8.
      These infants can be safely discharged from the hospital shortly after birth.

PMID- 19395396
TI  - Is universal prevention against youths' substance misuse really universal? Gender
      specific effects in the EU-Dap school-based prevention trial.
AB  - BACKGROUND: Studies of effectiveness of school-based prevention of substance
      misuse have generally overlooked gender differences. The purpose of this work was
      to analyse gender differences in the effectiveness of a new European school-based
      curriculum for prevention of substance misuse among adolescents. METHODS: The
      European Drug Abuse Prevention (EU-Dap) trial took place in seven European
      countries during the school year 2004-05. Schools were randomly assigned to
      either a control group or a 12-session standardised curriculum ("Unplugged")
      based on a comprehensive social influence model. The analytical sample consisted
      of 6359 students (3324 boys and 3035 girls). The use of cigarettes, alcohol and
      illicit drugs, adolescents' knowledge and opinions about substances, as well as
      social and personal skills were investigated through a self-completed anonymous
      questionnaire administered at enrollment and 3 months after the end of the
      programme. Adjusted Prevalence Odds Ratios were calculated as the measure of
      association between the intervention and behavioural outcomes using multilevel
      regression modelling. RESULTS: At enrollment, boys were more likely than girls to
      have used cannabis and illicit drugs, whereas girls had a higher prevalence of
      cigarette smoking. At the follow-up survey, a significant association between the
      programme and a lower prevalence of all behavioural outcomes was found among
      boys, but not among girls. Age and self-esteem emerged as possible modifiers of
      these gender differences, but effects were not statistically significant.
      CONCLUSIONS: Comprehensive social influence school curricula against substance
      misuse in adolescence may perform differently among girls and boys, owing to
      developmental and personality factors.

PMID- 19395397
TI  - Maternal social characteristics and mortality from injuries among infants and
      toddlers in Estonia.
AB  - BACKGROUND: Injuries are a major cause of ill health among children, with a
      social gradient in child injuries documented in many countries. The effects of
      maternal sociodemographic characteristics on injury mortality in Estonian infants
      and toddlers were investigated. METHODS: A population-based study using linkage
      of data from the Estonian Medical Birth Registry with Mortality Database. A total
      of 148 521 children born 1992-2002 were followed for injury mortality (ICD-9 E800
      E999) from birth to third birthday. Associations of maternal age, education,
      marital status, nationality, place of residence and child's birth order and
      multiplicity with risk of injury death were studied using logistic regression.
      RESULTS: Maternal age (<20 years compared with > or =30 years: OR 2.12; 95% CI
      1.00 to 4.51), education (basic compared with secondary or higher: OR 3.22; 95%
      CI 2.12 to 4.87), marital status (single, divorced or widowed compared with
      married: OR 2.74; 95% CI 1.53 to 4.91), nationality (other compared with
      Estonian: OR 2.00; 95% CI 1.32 to 3.02), birth order (fourth or higher compared
      with first: OR 6.66; 95% CI 3.42 to 12.99), and multiple birth (twin or triplet
      compared with singleton: OR 3.12; 95% CI 1.44 to 6.73) affected the risk of
      injury death among infants (<1 year). Among toddlers (1-2 years), boys were at
      higher risk than girls (OR 1.75; 95% CI 1.15 to 2.66) and low mother's education
      (basic compared with secondary or higher OR 2.08; 95% CI 1.28 to 3.37) and high
      birth order (fourth or higher compared with first: OR 7.88; 95% CI 3.90 to 15.90)
      increased the risk of injury death. CONCLUSIONS: Maternal sociodemographic
      characteristics are associated with injury mortality among infants and toddlers.
      Substantial variation in injury mortality rates within Estonia suggests potential
      for prevention.

PMID- 19395398
TI  - The impact of imprisonment on health: what do women prisoners say?
AB  - BACKGROUND: Women prisoners tend to suffer poor health on a range of indicators.
      This study sought to explore women prisoners' perceptions of the impact of
      imprisonment on their health. METHODS: This qualitative study involved adult
      women prisoners in two closed local prisons. Focus groups and individual
      interviews were conducted. RESULTS: Women prisoners reported that imprisonment
      impacted negatively upon their health. The initial shock of imprisonment,
      separation from families and enforced living with other women suffering drug
      withdrawal and serious mental health problems affected their own mental health.
      Over the longer term, women complained of detention in unhygienic facilities by
      regimes that operated to disempower them, including in the management of their
      own health. Women described responses to imprisonment that were also health
      negating such as increased smoking, eating poorly and seeking psychotropic
      medication. However, imprisonment could also offer a respite from lives
      characterised by poverty, social exclusion, substance misuse and violence, with
      perceived improvements in health. CONCLUSION: The impact of imprisonment on
      women's health was mixed but was largely perceived to be negative. Despite policy
      initiatives to introduce health promotion in prisons, there is little evidence of
      the extent to which this has been effective. The current policy climate in the UK
      makes it especially timely to examine the reported experience of women prisoners
      themselves about the impact of imprisonment on their health and to re-evaluate
      health promotion in women's prisons.

PMID- 19395399
TI  - Making choices: why parents present to the emergency department for non-urgent
      care.
AB  - OBJECTIVES: This study aims to provide a better understanding of the motivations
      and actions of parents of children with non-urgent injury or illness who attend
      the emergency department at a tertiary paediatric hospital seeking care. DESIGN:
      A prospective questionnaire-based survey of 355 parents aimed to ascertain
      information about parent care-giving and care-seeking behaviours prior to
      presentation at the emergency department with their child. RESULTS: A total of
      355 parents were surveyed, representing 8% of the parents/carers presenting to
      the emergency department in a 3-month period for non-urgent (Australasian Triage
      System 4 and 5) care of their child. The factors identified were: parents rated
      their child's condition as moderate to very serious (242 (68%)); two-thirds of
      parents (234 (66%)) had sought advice prior to attending the emergency
      department; 54% (77) of the 137 children who attended with an injury presented
      promptly to emergency (ie, within 4 h of injury) whereas of the 216 presenting
      with an illness, 41% (88) presented within 2-7 days of the onset of the illness.
      CONCLUSIONS: This study displayed the accuracy of "parental triage," that is,
      parents assess their child's health and generally engage in appropriate care
      giving and care-seeking behaviours before presenting to a paediatric emergency
      department. Highlighted are the deficiencies in current primary care services
      available to families and the perception that not all cases deemed as non-urgent
      by the emergency department are able to be dealt with in a primary care setting.

PMID- 19395400
TI  - The Young Everest Study: effects of hypoxia at high altitude on cardiorespiratory
      function and general well-being in healthy children.
AB  - OBJECTIVES: To assess the effect of altitude and acclimatisation on
      cardiorespiratory function and well-being in healthy children. METHODS: A daily
      symptom diary, serial measurements of spirometry, end-tidal carbon dioxide
      (etCO(2)) and daytime and overnight pulse oximetry (SpO(2)), were undertaken at
      sea level and altitudes up to 3500 m in healthy children during a trekking
      holiday. SpO(2) at altitude was compared with that in flight and during acute
      hypoxic challenge (breathing 15% oxygen) at sea level. RESULTS: Measurements were
      obtained in nine children aged 6-13 years (median 8). SpO(2) decreased
      significantly during the hypoxic challenge (difference -5%, 95% CI -6 to -3%,
      p<0.01) but remained above 90% in all children. There was a significant fall in
      daytime and overnight SpO(2) (95% CI -11.9 to -7.5% and -12 to -8, respectively)
      and etCO(2) (-8.5 to -4.5 mm Hg) as the children ascended to 3500 m. There was a
      significant increase in SpO(2) (95% CI 1.1 to 4.9%) and a further drop in etCO(2)
      (-5.9 to -0.8 mm Hg) after a week at altitude, etCO(2) being negatively
      correlated with SpO(2). There was no correlation between SpO(2) during hypoxic
      challenge, in flight or at altitude. Lung function remained within 7% of baseline
      in all but two children, in whom reductions of up to 23% in FVC and 16% FEV(1)
      were observed at altitude. The children generally remained well, but the Lake
      Louise scoring system was unreliable in this age group. CONCLUSIONS: A wide range
      of physiological responses to altitude are evident in healthy children. This
      study should inform future larger studies in children to improve understanding of
      responses to hypoxia in health and disease.

PMID- 19395401
TI  - Chlamydia trachomatis respiratory infection in Dutch infants.
AB  - Chlamydia trachomatis is the most common bacterial pathogen causing sexually
      transmitted infections in Dutch adults. As prenatal screening for C trachomatis
      and treatment of pregnant women is not routine practice in The Netherlands,
      perinatal transmission of C trachomatis may therefore occur. The presence of C
      trachomatis in infants less than 6 months of age who presented with respiratory
      complaints to the Erasmus MC-Sophia hospital was evaluated. Respiratory
      specimens, primarily nasopharyngeal swabs, were tested for C trachomatis,
      respiratory viruses and Mycoplasma pneumoniae using PCR, viral isolation in cell
      cultures and direct immunofluorescence. C trachomatis respiratory tract infection
      was confirmed to be relatively common with detection in 10 of 148 (7%) infants
      tested. C trachomatis had not been tested for by the attending physicians, but
      was the second most frequently detected respiratory pathogen after human
      Respiratory Syncitial Virus, which was found in 41 (28%) infants.

PMID- 19395402
TI  - Effect of a minimal pharmacy intervention on improvement of adherence to asthma
      guidelines.
AB  - OBJECTIVE: To study the effectiveness of a minimal intervention strategy to
      improve adherence to paediatric asthma guidelines. DESIGN AND SETTING: A group of
      pharmacists was encouraged to discuss essential elements of asthma care with the
      general practitioners they normally worked with. Adherence to guidelines was
      evaluated by studying prescriptions for children with asthma. We compared the
      treatment of children registered at pharmacies which participated in the study
      (intervention group) with a control group of children registered at other, non
      participating pharmacies (reference group) and with the results of an earlier
      study. MAIN OUTCOME MEASURES: The numbers of children who had no short-acting
      betamimetics, no inhaled corticosteroids while on long-acting betamimetics, and
      more than one type of inhaler. RESULTS: The number of children who had no short
      acting betamimetics was significantly lower in the intervention group (176/1447
      vs 534/3527; p<0.01) and fewer children had no inhaled corticosteroid although on
      long-acting betamimetics (6/219 vs 41/477; p=0.03). The number of children who
      had more than one type of inhaler was equal in both groups (5.1%), but this was
      significantly lower compared with the earlier study (119/2311 vs 239/3217;
      p<0.01). CONCLUSIONS: The assistance of pharmacists with adherence to paediatric
      asthma guidelines is beneficial. Pharmacists should be involved actively in the
      care of children with asthma.

PMID- 19395403
TI  - Children in emergency departments: who should provide their care?

PMID- 19395404
TI  - Monitoring of home safety issues in children on enteral feeds with inherited
      metabolic disorders.
AB  - OBJECTIVE: To assess the safety aspects of carers' enteral feeding technique when
      home enteral tube feeding children with inherited metabolic disorders (IMD).
      METHODS: 40 patients (median age, 5.1 years; range, 0.3-13.6 years) with IMD
      requiring pump tube feeding were recruited. 12 patients had glycogen storage
      disease, 11 organic acidemias, 8 fatty acid oxidation disorders, 4 urea cycle
      disorders, and 5 had other conditions. 50% of the patients were fed by
      gastrostomy and 50% nasogastric tube. A questionnaire and practical assessment of
      feeding process was completed with carers by a dietician and nurse in the child's
      home. Areas investigated included carer hygiene, feed preparation, tube care,
      tube changing, use of feeding pumps and equipment, and storage of enteral feeding
      equipment. RESULTS: The main issues identified were poor hygiene practices (78%
      unclean work surfaces; 25% no hand washing); inaccurate ingredient measuring
      (40%); irregular checking of tube position (40%); inadequate tube flushing (50%);
      poor knowledge of how to clear tube blockages (80%); incorrect priming of pump
      sets (50%); incorrect position of child for night feeding (63%); untrained
      secondary carers (43%); and poor knowledge of pump alarms, battery life, and
      charging time. Children commonly slept in parent's room as a safety precaution
      (58%). CONCLUSIONS: Long term follow-up of children with IMD on home enteral tube
      feeding suggests that regular updates on knowledge and technique for carers may
      be necessary to reduce risk.

PMID- 19395405
TI  - The wound-, pathogen-, and ultraviolet B-responsive MYB134 gene encodes an R2R3
      MYB transcription factor that regulates proanthocyanidin synthesis in poplar.
AB  - In poplar (Populus spp.), the major defense phenolics produced in leaves are the
      flavonoid-derived proanthocyanidins (PAs) and the salicin-based phenolic
      glycosides. Transcriptional activation of PA biosynthetic genes leading to PA
      accumulation in leaves occurs following herbivore damage and mechanical wounding
      as well as infection by the fungal biotroph Melampsora medusae. In this study, we
      have identified a poplar R2R3 MYB transcription factor gene, MYB134, that
      exhibits close sequence similarity to the Arabidopsis (Arabidopsis thaliana) PA
      regulator TRANSPARENT TESTA2 and that is coinduced with PA biosynthetic genes
      following mechanical wounding, M. medusae infection, and exposure to elevated
      ultraviolet B light. Overexpression of MYB134 in poplar resulted in
      transcriptional activation of the full PA biosynthetic pathway and a significant
      plant-wide increase in PA levels, and electrophoretic mobility shift assays
      showed that recombinant MYB134 protein is able to bind to promoter regions of PA
      pathway genes. MYB134-overexpressing plants exhibited a concomitant reduction in
      phenolic glycoside concentrations and other minor alterations to levels of small
      phenylpropanoid metabolites. Our data provide insight into the regulatory
      mechanisms controlling stress-induced PA metabolism in poplar, and the
      identification of a regulator of stress-responsive PA biosynthesis constitutes a
      valuable tool for manipulating PA metabolism in poplar and investigating the
      biological functions of PAs in resistance to biotic and abiotic stresses.

PMID- 19395406
TI  - The two plastidial starch-related dikinases sequentially phosphorylate glucosyl
      residues at the surface of both the A- and B-type allomorphs of crystallized
      maltodextrins but the mode of action differs.
AB  - In this study, two crystallized maltodextrins were generated that consist of the
      same oligoglucan pattern but differ strikingly in the physical order of double
      helices. As revealed by x-ray diffraction, they represent the highly ordered A-
      and B-type allomorphs. Both crystallized maltodextrins were similar in size
      distribution and birefringence. They were used as model substrates to study the
      consecutive action of the two starch-related dikinases, the glucan, water
      dikinase and the phosphoglucan, water dikinase. The glucan, water dikinase and
      the phosphoglucan, water dikinase selectively esterify glucosyl residues in the
      C6 and C3 positions, respectively. Recombinant glucan, water dikinase
      phosphorylated both allomorphs with similar rates and caused complete glucan
      solubilization. Soluble neutral maltodextrins inhibited the glucan, water
      dikinase-mediated phosphorylation of crystalline particles. Recombinant
      phosphoglucan, water dikinase phosphorylated both the A- and B-type allomorphs
      only following a prephosphorylation by the glucan, water dikinase, and the
      activity increased with the extent of prephosphorylation. The action of the
      phosphoglucan, water dikinase on the prephosphorylated A- and B-type allomorphs
      differed. When acting on the B-type allomorph, by far more phosphoglucans were
      solubilized as compared with the A type. However, with both allomorphs, the
      phosphoglucan, water dikinase formed significant amounts of monophosphorylated
      phosphoglucans. Thus, the enzyme is capable of acting on neutral maltodextrins.
      It is concluded that the actual carbohydrate substrate of the phosphoglucan,
      water dikinase is defined by physical rather than by chemical parameters. A model
      is proposed that explains, at the molecular level, the consecutive action of the
      two starch-related dikinases.

PMID- 19395407
TI  - AMR1, an Arabidopsis gene that coordinately and negatively regulates the
      mannose/l-galactose ascorbic acid biosynthetic pathway.
AB  - Ascorbic acid (AsA) biosynthesis in plants occurs through a complex,
      interconnected network with mannose (Man), myoinositol, and galacturonic acid as
      principal entry points. Regulation within and between pathways in the network is
      largely uncharacterized. A gene that regulates the Man/l-galactose (l-Gal) AsA
      pathway, AMR1 (for ascorbic acid mannose pathway regulator 1), was identified in
      an activation-tagged Arabidopsis (Arabidopsis thaliana) ozone-sensitive mutant
      that had 60% less leaf AsA than wild-type plants. In contrast, two independent T
      DNA knockout lines disrupting AMR1 accumulated 2- to 3-fold greater foliar AsA
      and were more ozone tolerant than wild-type controls. Real-time reverse
      transcription-polymerase chain reaction analysis of steady-state transcripts of
      genes involved in AsA biosynthesis showed that AMR1 negatively affected the
      expression of GDP-Man pyrophosphorylase, GDP-l-Gal phosphorylase, l-Gal-1
      phosphate phosphatase, GDP-Man-3',5'-epimerase, l-Gal dehydrogenase, and l
      galactono-1,4-lactone dehydrogenase, early and late enzymes of the Man/l-Gal
      pathway to AsA. AMR1 expression appears to be developmentally and environmentally
      controlled. As leaves aged, AMR1 transcripts accumulated with a concomitant
      decrease in AsA. AMR1 transcripts also decreased with increased light intensity.
      Thus, AMR1 appears to play an important role in modulating AsA levels in
      Arabidopsis by regulating the expression of major pathway genes in response to
      developmental and environmental cues.

PMID- 19395408
TI  - Antisense down-regulation of the FaPG1 gene reveals an unexpected central role
      for polygalacturonase in strawberry fruit softening.
AB  - The strawberry (Fragaria x ananassa 'Chandler') fruit undergoes a fast softening
      during ripening. Polygalacturonase (PG) activity is low during this process, but
      two ripening-related PG genes, FaPG1 and FaPG2, have been cloned. Both genes were
      up-regulated during fruit ripening and were also negatively regulated by auxin.
      To further assess the role of FaPG1 on strawberry softening, transgenic plants
      containing an antisense sequence of this gene under the control of the 35S
      promoter (APG lines) were obtained. Sixteen out of 30 independent transgenic
      lines showed fruit yields similar to those of the control. Several quality
      parameters were measured in ripe fruits from these 16 lines. Fruit weight was
      slightly reduced in four lines, and most of them showed an increase in soluble
      solid content. Half of these lines yielded fruits significantly firmer than did
      the control. Four APG lines were selected, their ripened fruits being on average
      163% firmer than the control. The postharvest softening of APG fruits was also
      diminished. Ripened fruits from the four selected lines showed a 90% to 95%
      decrease in FaPG1 transcript abundance, whereas the level of FaPG2 was not
      significantly altered. Total PG activity was reduced in three of these lines when
      compared with control fruits. Cell wall extracts from APG fruits showed a
      reduction in pectin solubilization and an increase in pectins covalently bound to
      the cell wall. A comparative transcriptomic analysis of gene expression between
      the ripened receptacle of the control and those of the APG fruits (comprising
      1,250 receptacle expressed sequence tags) did not show any statistically
      significant change. These results indicate that FaPG1 plays a central role in
      strawberry softening.

PMID- 19395409
TI  - BIN2 functions redundantly with other Arabidopsis GSK3-like kinases to regulate
      brassinosteroid signaling.
AB  - GLYCOGEN SYNTHASE KINASE3 (GSK3) is a highly conserved serine/threonine kinase
      involved in a variety of developmental signaling processes. The Arabidopsis
      (Arabidopsis thaliana) genome encodes 10 GSK3-like kinases that are clustered
      into four groups. Forward genetic screens have so far uncovered eight mutants,
      all of which carry gain-of-function mutations in BRASSINOSTEROID-INSENSITIVE2
      (BIN2), one of the three members in group II. Genetic and biochemical studies
      have implicated a negative regulatory role for BIN2 in brassinosteroid (BR)
      signaling. Here, we report the identification of eight ethyl methanesulfonate
      mutagenized loss-of-function bin2 alleles and one T-DNA insertional mutation each
      for BIN2 and its two closest homologs, BIN2-Like1 and BIN2-Like2. Our genetic,
      biochemical, and physiological assays revealed that despite functional
      redundancy, BIN2 plays a dominant role among the three group II members in
      regulating BR signaling. Surprisingly, the bin2bil1bil2 triple T-DNA insertional
      mutant still responds to BR and accumulates a more phosphorylated form of a BIN2
      substrate than the wild-type plant. Using the specific GSK3 inhibitor lithium
      chloride, we have provided strong circumstantial evidence for the involvement of
      other Arabidopsis GSK3-like kinases in BR signaling. Interestingly, lithium
      chloride treatment was able to suppress the gain-of-function bin2-1 mutation but
      had a much weaker effect on a strong BR receptor mutant, suggesting the presence
      of a BIN2-independent regulatory step downstream of BR receptor activation.

PMID- 19395410
TI  - The cytokinin type-B response regulator PtRR13 is a negative regulator of
      adventitious root development in Populus.
AB  - Adventitious root formation at the base of plant cuttings is an innate de novo
      organogenesis process that allows massive vegetative propagation of many
      economically and ecologically important species. The early molecular events
      following shoot excision are not well understood. Using whole-genome microarrays,
      we detected significant transcriptome remodeling during 48 h following shoot
      removal in Populus tremula x Populus alba softwood cuttings in the absence of
      exogenous auxin, with 27% and 36% of the gene models showing differential
      abundance between 0 and 6 h and between 6 and 24 h, respectively. During these
      two time intervals, gene networks involved in protein turnover, protein
      phosphorylation, molecular transport, and translation were among the most
      significantly regulated. Transgenic lines expressing a constitutively active form
      of the Populus type-B cytokinin response regulator PtRR13 (DeltaDDKPtRR13) have a
      delayed rooting phenotype and cause misregulation of CONTINUOUS VASCULAR RING1, a
      negative regulator of vascularization; PLEIOTROPIC DRUG RESISTANCE TRANSPORTER9,
      an auxin efflux transporter; and two APETALA2/ETHYLENE RESPONSE FACTOR genes with
      sequence similarity to TINY. Inappropriate cytokinin action via DeltaDDKPtRR13
      expression appeared to disrupt adventitious root development 24 h after shoot
      excision, when root founder cells are hypothesized to be sensitive to the
      negative effects of cytokinin. Our results are consistent with PtRR13 acting
      downstream of cytokinin to repress adventitious root formation in intact plants,
      and that reduced cytokinin signaling after shoot excision enables coordinated
      expression of ethylene, auxin, and vascularization pathways leading to
      adventitious root development.

PMID- 19395413
TI  - Molecular mechanism of seed coat discoloration induced by low temperature in
      yellow soybean.
AB  - Seed coat pigmentation is inhibited in yellow soybean. The I gene inhibits
      pigmentation over the entire seed coat. In yellow soybean, seed coat
      discoloration occurs when plants are exposed to low temperatures after the onset
      of flowering, a phenomenon named 'cold-induced discoloration (CD)'. Inhibition of
      seed coat pigmentation results from post-transcriptional gene silencing (PTGS) of
      the chalcone synthase (CHS) genes. PTGS is a sequence-specific RNA degradation
      mechanism in plants and occurs via short interfering RNAs (siRNAs). Similar post
      transcriptional suppression is called RNAi (RNA interference) in animals.
      Recently, we identified a candidate of the I gene designated GmIRCHS. In this
      study, to elucidate the molecular mechanism of CD, CHS mRNA and siRNA levels in
      the seed coat were compared between CD-sensitive and CD-tolerant cultivars
      (Toyomusume and Toyoharuka, respectively). In Toyomusume, the CHS siRNA level was
      reduced markedly by low temperature treatment, and subsequently the CHS mRNA
      level increased rapidly after treatment. In contrast, low temperature treatment
      did not result in severe reduction of the CHS siRNA level in Toyoharuka, and the
      CHS mRNA level did not increase after the treatment. These results suggest that
      the rapid increase in CHS mRNA level after low temperature treatment may lead to
      enhanced pigmentation in some of the seed coat cells and finally in seed coat
      discoloration. Interestingly, we found a Toyoharuka-specific difference in the
      GmIRCHS region, which may be involved in CD tolerance.

PMID- 19395411
TI  - Arabidopsis IAR4 modulates auxin response by regulating auxin homeostasis.
AB  - In a screen for enhancers of tir1-1 auxin resistance, we identified two novel
      alleles of the putative mitochondrial pyruvate dehydrogenase E1alpha-subunit, IAA
      Alanine Resistant4 (IAR4). In addition to enhancing the auxin response defects of
      tir1-1, iar4 single mutants exhibit numerous auxin-related phenotypes including
      auxin-resistant root growth and reduced lateral root development, as well as
      defects in primary root growth, root hair initiation, and root hair elongation.
      Remarkably, all of these iar4 mutant phenotypes were rescued when endogenous
      indole-3-acetic acid (IAA) levels were increased by growth at high temperature or
      overexpression of the YUCCA1 IAA biosynthetic enzyme, suggesting that iar4
      mutations may alter IAA homeostasis rather than auxin response. Consistent with
      this possibility, iar4 mutants exhibit increased Aux/IAA stability compared to
      wild type under basal conditions, but not in response to an auxin treatment.
      Measurements of free IAA levels detected no significant difference between iar4-3
      and wild-type controls. However, we consistently observed significantly higher
      levels of IAA-amino acid conjugates in the iar4-3 mutant. Furthermore, using
      stable isotope-labeled IAA precursors, we observed a significant increase in the
      relative utilization of the Trp-independent IAA biosynthetic pathway in iar4-3.
      We therefore suggest that the auxin phenotypes of iar4 mutants are the result of
      altered IAA homeostasis.

PMID- 19395414
TI  - Down-regulation of PoGT47C expression in poplar results in a reduced
      glucuronoxylan content and an increased wood digestibility by cellulase.
AB  - Xylan is the second most abundant polysaccharide in dicot wood. Unraveling the
      biosynthetic pathway of xylan is important not only for our understanding of the
      process of wood formation but also for our rational engineering of wood for
      biofuel production. Although several glycosyltransferases are implicated in
      glucuronoxylan (GX) biosynthesis in Arabidopsis, whether their close orthologs in
      woody tree species are essential for GX biosynthesis during wood formation has
      not been investigated. In fact, no studies have been reported to evaluate the
      effects of alterations in secondary wall-associated glycosyltransferases on wood
      formation in tree species. In this report, we demonstrate that PoGT47C, a poplar
      glycosyltransferase belonging to family GT47, is essential for the normal
      biosynthesis of GX and the normal secondary wall thickening in the wood of the
      hybrid poplar Populus alba x tremula. RNA interference (RNAi) inhibition of
      PoGT47C resulted in a drastic reduction in the thickness of secondary walls, a
      deformation of vessels and a decreased amount of GX in poplar wood. Structural
      analysis of GX using nuclear magnetic resonance (NMR) spectroscopy demonstrated
      that the reducing end of GX from poplar wood contains the tetrasaccharide
      sequence, beta-d-Xylp-(1-->3)-alpha-l-Rhap-(1-->2)-alpha-d-GalpA-(1-->4)-d-Xylp,
      and that its abundance was significantly decreased in the GX from the wood of the
      GT47C-RNAi lines. The transgenic wood was found to yield more glucose by
      cellulase digestion than the wild-type wood, indicating that the GX reduction in
      wood reduces the recalcitrance of wood to cellulase digestion. Together, these
      results provide direct evidence demonstrating that the PoGT47C
      glycosyltransferase is essential for normal GX biosynthesis in poplar wood and
      that GX modification could improve the digestibility of wood cellulose by
      cellulase.

PMID- 19395415
TI  - Diabetes, kidney disease and cardiovascular disease patients. Assessing care of
      complex patients using outpatient testing and visits: additional metrics by which
      to evaluate health care system functioning.
AB  - BACKGROUND: The triad of cardiovascular disease (CVD), chronic kidney disease
      (CKD) and diabetes mellitus (DM) share many fundamental disease pathways.
      Patients with these conditions contribute excessively to health care costs.
      Opportunities for system redesign require metrics by which to evaluate the
      impact. METHODS: Using a provincial comprehensive set of administrative billing
      databases (outpatient visits, laboratory tests, pharmacy and hospital inpatient
      services), we itemized the prevalence of each and combination of conditions,
      resource utilization associated with each condition and combinations, using ICD 9
      10 billing codes and standard definitions. Three consecutive years (2003-2005)
      were used to establish stability of findings. RESULTS: CKD, CVD and DM diagnoses
      are found in 422 124 persons within a province of 4.3 million individuals (10%);
      1.7% had all three conditions. The median age of each cohort varied significantly
      between those with multiple conditions (67-79 years) versus those with single
      condition (56-72 years). The median number of physician visits was 26 per patient
      year. Duplicate testing accounted for expenditures of $3 million/annum; 7.55% of
      patients accounted for 34.4% of duplicate tests. Those with DM or CKD had similar
      use of medications, physician visits and hospital days. Those with all conditions
      (CVD-CKD-DM) had a median of 6 in-hospital days/year. A significant proportion
      were not on ACE/ARB or statin medications (30 and 45%, respectively). CONCLUSION:
      Patients with chronic, complex conditions consume a large number of outpatient
      and inpatient resources. Documenting these allows identification of a set of
      metrics by which to design and measure health care system redesign initiatives.
      Potential targets to benchmark in designing more effective systems have been
      identified.

PMID- 19395416
TI  - Ventricular fibrillation induced by a radiofrequency energy delivery for
      idiopathic premature ventricular contractions arising from the left ventricular
      anterior papillary muscle.
AB  - A 73-year-old man with idiopathic premature ventricular contractions (PVCs)
      underwent electrophysiological testing. Left ventricular activation mapping
      revealed a focal mechanism of the PVCs with the earliest activation on the
      anterior papillary muscle (APM). Irrigated radiofrequency (RF) current delivered
      at that site induced a cluster of non-sustained ventricular tachycardia episodes
      with the same QRS morphology as the PVCs, followed by ventricular fibrillation
      (VF). The APM might have served as an abnormal automatic trigger and driver for
      the VF occurrence. Ventricular fibrillation may occur as a complication during RF
      catheter ablation of papillary muscle ventricular arrhythmias even if the
      clinical arrhythmia is limited to PVCs.

PMID- 19395417
TI  - Rapid and low-cost method to prove the nature of no documented tachycardia in
      children and teenagers without pre-excitation syndrome.
AB  - Aims Symptoms in children are often difficult to interpret. The purpose of this
      study was to report the results of transoesophageal electrophysiological study
      (EPS) performed in children complaining of sudden onset tachycardia with normal
      non-invasive studies. Methods and results Eighty-two children and teenagers (mean
      age 15 +/- 3 years) presented with suspected but no documented paroxysmal
      supraventricular tachycardia (SVT). ECG was normal. Non-invasive studies were
      negative; 23 children had syncope with tachycardias. They underwent
      transoesophageal EPS in our out-patient clinic. The mean duration of
      transoesophageal EPS was 11 +/- 5 min. Electrophysiological study was negative in
      25 children. AV nodal re-entrant tachycardia could be induced in 37 children, 11
      of them associated with syncope. Wolff-Parkinson-White syndrome (WPW) was
      diagnosed in five children in which atrioventricular re-entrant tachycardia was
      inducible. Atrioventricular re-entrant tachycardia due to a concealed AP was
      induced in 14 children. Verapamil-sensitive ventricular tachycardia was induced
      in one patient. Factors associated with tachycardia inducibility were an older
      age (15.5 +/- 2 vs. 14 +/- 4 years) (P < 0.05) and the absence of syncope (81 vs.
      52%) (P < 0.05). During a mean follow-up of 3 +/- 1 year, no patient with
      negative EPS developed documented tachycardia. In 17 children with inducible SVT,
      radiofrequency ablation of the re-entrant circuit was subsequently performed.
      Conclusion Transoesophageal EPS is a fast method for proving the nature of
      paroxysmal tachycardia in children and teenagers presenting with normal ECG and
      for demonstrating WPW syndrome not visible on standard ECG. The negative
      predictive value of transoesophageal EPS for the diagnosis of SVT was 100%.

PMID- 19395418
TI  - Chronic cough in adults.

PMID- 19395419
TI  - Diagnosis using "test of treatment".

PMID- 19395422
TI  - At what age should cervical screening stop?

PMID- 19395420
TI  - Incidence of cervical cancer after several negative smear results by age 50:
      prospective observational study.
AB  - OBJECTIVE: To determine the incidence of cervical cancer after several negative
      cervical smear tests at different ages. DESIGN: Prospective observational study
      of incidence of cervical cancer after the third consecutive negative result based
      on individual level data in a national registry of histopathology and
      cytopathology (PALGA). SETTING: Netherlands, national data. Population 218,847
      women aged 45-54 and 445,382 aged 30-44 at the time of the third negative smear
      test. MAIN OUTCOME MEASURES: 10 year cumulative incidence of interval cervical
      cancer. RESULTS: 105 women developed cervical cancer within 2 595,964 woman years
      at risk after the third negative result at age 30-44 and 42 within 1,278,532
      woman years at risk after age 45-54. During follow-up, both age groups had
      similar levels of screening. After 10 years of follow-up, the cumulative
      incidence rate of cervical cancer was similar: 41/100,000 (95% confidence
      interval 33 to 51) in the younger group and 36/100,000 (24 to 52) in the older
      group (P=0.48). The cumulative incidence rate of cervical intraepithelial
      neoplasia grade I+ was twice as high in the younger than in the older group
      (P<0.001). CONCLUSIONS: The risk for cervical cancer after several negative smear
      results by age 50 is similar to the risk at younger ages. Even after several
      negative smear results, age is not a good discriminative factor for early
      cessation of cervical cancer screening.

PMID- 19395423
TI  - Childhood disability and social policies.

PMID- 19395424
TI  - Participation in life situations of 8-12 year old children with cerebral palsy:
      cross sectional European study.
AB  - OBJECTIVES: To evaluate how involvement in life situations (participation) in
      children with cerebral palsy varies with type and severity of impairment and to
      investigate geographical variation in participation. DESIGN: Cross sectional
      study. Trained interviewers visited parents of children with cerebral palsy;
      multilevel multivariable regression related participation to impairments, pain,
      and sociodemographic characteristics. SETTING: Eight European regions with
      population registers of children with cerebral palsy; one further region
      recruited children from multiple sources. PARTICIPANTS: 1174 children aged 8-12
      with cerebral palsy randomly selected from the population registers, 743 (63%)
      joined in the study; the further region recruited 75 children. MAIN OUTCOME
      MEASURE: Children's participation assessed by the Life-H questionnaire covering
      10 main areas of daily life. Scoring ignored adaptations or assistance required
      for participation. RESULTS: Children with pain and those with more severely
      impaired walking, fine motor skills, communication, and intellectual abilities
      had lower participation across most domains. Type of cerebral palsy and problems
      with feeding and vision were associated with lower participation for specific
      domains, but the sociodemographic factors examined were not. Impairment and pain
      accounted for up to a sixth of the variation in participation. Participation on
      all domains varied substantially between regions: children in east Denmark had
      consistently higher participation than children in other regions. For most
      participation domains, about a third of the unexplained variation could be
      ascribed to variation between regions and about two thirds to variation between
      individuals. CONCLUSIONS: Participation in children with cerebral palsy should be
      assessed in clinical practice to guide intervention and assess its effect. Pain
      should be carefully assessed. Some European countries facilitate participation
      better than others, implying some countries could make better provision.
      Legislation and regulation should be directed to ensuring this happens.

PMID- 19395425
TI  - Orosomucoid influences the response to antidepressants in major depressive
      disorder.
AB  - Orosomucoid, an acute phase protein, carries basic drugs including
      antidepressants in plasma. Elevated levels have been reported in patients with
      depression. It has yet to be established whether orosomucoid concentration
      influences antidepressant response. The orosomucoid gene (ORM1) is polymorphic
      and the protein isoforms have differing pharmacokinetic properties which could
      alter plasma profile and blood brain barrier transport of antidepressants.
      Outpatients (n = 157) in a randomised control trial of fluoxetine versus
      nortriptyline were genotyped for the ORM1 variants. Plasma concentrations of
      acute phase proteins were also measured. Outcomes were the completion of an
      adequate six week trial of antidepressant and response. Response was defined as
      an improvement >/=60% on the Montgomery-Asperg Depression Rating Scale (MADRS)
      over six weeks. The first notable finding was that individuals with an ORM1*S/*S
      genotype were less likely to complete an adequate six week trial of an
      antidepressant (OR = 4.707, 95% CI 1.769-12.527, P = 0.002). The second was that
      higher orosomucoid concentrations were found in antidepressant non-responders
      (91.4%) than responders (79.1%) (F1, 106 = 5.669, P = 0.019). These findings
      highlight the potential importance of variables such as orosomucoid which impact
      on drug availability on the therapeutic efficacy of antidepressant drugs.

PMID- 19395426
TI  - Relationship between response to risperidone, plasma concentrations of
      risperidone and CYP3A4 polymorphisms in schizophrenia patients.
AB  - In this study, we examined the relationships between plasma concentrations of
      risperidone and 9-hydroxyrisperidone and polymorphisms of CYP3A4. All 130
      schizophrenia patients (45 men, 85 women, age 15-60 years) who met DSM-IV
      criteria were given risperidone for 8 weeks. Clinical efficacy was determined
      using the Positive and Negative Syndrome Scale (PANSS). CYP3A4*1G was found to be
      associated with the change in total PANSS scores (Kruskal-Wallis test, P =
      0.021), which was not significant on adjusting for multiple testing. Our study
      has, for the first time, conducted a genetic association study of the CYP3A4 gene
      with risperidone response. Further studies on larger groups and on the effects of
      the longer term risperidone treatment are needed to confirm these results.

PMID- 19395427
TI  - Can atypical antipsychotics improve tardive dyskinesia associated with other
      atypical antipsychotics? Case report and brief review of the literature.
AB  - Tardive dyskinesia (TD) is a devastating adverse effect of long-term
      antipsychotic drug treatment. Atypical antipsychotics produce less TD, and it has
      been shown that they may have a therapeutic effect on pre-existing TD. Here, we
      report a case of olanzapine-induced TD which did not improve after switching to
      risperidone but improved after the addition of quetiapine to risperidone regimen.
      We also provide a brief review of the reported cases on TD induced by atypical
      antipsychotics which improved after switching to another atypical agent. It is
      unclear whether some atypical antipsychotics are more effective than others in
      the treatment of TD. Differences in this property and the underlying mechanism
      require further study.

PMID- 19395429
TI  - Characterisation of the effects of caffeine on sleep in the rat: a potential
      model of sleep disruption.
AB  - Caffeine is known to disrupt sleep and its administration to human subjects has
      been used to model sleep disruption. We previously showed that its effects on
      sleep onset latency are comparable between rats and humans. This study evaluated
      the potential use of caffeine as a model of sleep disruption in the rat, by
      assessing its effects on sleep architecture and electroencephalogram (EEG)
      frequency spectrum, and using sleep-promoting drugs to reverse these effects.
      Rats were implanted with radiotelemetry devices for body temperature, EEG,
      electromyogram and locomotor activity. Following recovery, animals were dosed
      with caffeine (10 mg/kg) alone or in combination with zolpidem (10 mg/kg) or
      trazodone (20 mg/kg). Sleep was scored for the subsequent 12 h using automated
      analysis software. Caffeine dose-dependently disrupted sleep: it increased WAKE
      time, decreased NREM (non-REM) sleep time and NREM bout duration (but not bout
      number), and decreased delta activity in NREM sleep. It also dose-dependently
      increased locomotor activity and body temperature. When given alone, zolpidem
      suppressed REM whilst trazodone increased NREM sleep time at the expense of WAKE,
      increased NREM bout duration, increased delta activity in NREM sleep and reduced
      body temperature. In combination, zolpidem attenuated caffeine's effects on WAKE,
      whilst trazodone attenuated its effects on NREM sleep, NREM bout duration, delta
      activity, body temperature and locomotor activity. Caffeine administration
      produced many of the signs of insomnia that were improved by two of its most
      successful current treatments. This model may therefore be useful in the study of
      new drugs for the treatment of sleep disturbance.

PMID- 19395428
TI  - STAR*D: a summary and UK perspective.

PMID- 19395430
TI  - Dissection of placebo analgesia in mice: the conditions for activation of opioid
      and non-opioid systems.
AB  - Amanzio and Benedetti (J Neurosci 1999; 19: 484-494) first addressed the
      conditions necessary for the activation of opioid and non-opioid placebo
      responses in human. Here, we investigated whether placebo analgesia is subdivided
      into opioid and non-opioid components in mice by using the model of hot-plate
      test. Drug conditioning was performed by the combination of the conditioned cue
      stimulus with the unconditioned drug stimulus, either opioid agonist morphine
      hydrochloride or non-opioid aspirin. Placebo analgesic responses were evoked by
      an exposure to a conditioned cue previously paired with drug conditioning.
      Morphine conditioning produced placebo responses that were completely antagonised
      by naloxone. By contrast, the conditioned cue after aspirin conditioning elicited
      a placebo effect that was not blocked by naloxone. Therefore, we first evoked
      opioid and non-opioid placebo responses in mice that were either naloxone
      reversible or naloxone-insensitive, depending on the drug used in conditioning
      procedure. These findings support that the mechanisms underlying placebo
      analgesia may depend on the drug conditioning that was originally performed. The
      present procedure of mice may serve as a model for further understanding of the
      opioid and non-opioid mechanisms underlying placebo responses.

PMID- 19395431
TI  - Commentary on STAR*D: a summary and UK perspective.

PMID- 19395432
TI  - Meta-analysis of the effects of lithium usage on serum creatinine levels.
AB  - There is conflicting evidence concerning lithium's effect on renal function. The
      aim is to clarify whether lithium affects kidney function and at what stage of
      treatment any effect may occur. Systematic review identified 23 studies split
      into three groups on which meta-analysis was performed to identify the following:
      A) lithium's effect on renal function in cross-sectional case-control studies, B)
      studies of renal function before and after commencement on lithium, C) studies of
      longer term effect in those already established on lithium therapy. Group A
      showed a statistically significant increase of 5.7 MUmol/L in creatinine in the
      study population compared with controls. Group B showed a non-statistically
      significant rise in creatinine (2.9 MUmol/L) after a mean follow-up of 86 months.
      Group C showed a statistically significant increase in creatinine of 7.0 MUmol/L
      over a mean duration of 64 months. An increase in creatinine of an average of 1.6
      MUmol/L/year on lithium was also identified in this group. Any lithium-associated
      increase in serum creatinine is quantitatively small and of questionable clinical
      significance. However, routine renal function monitoring of patients on lithium
      is essential.

PMID- 19395433
TI  - Mass spectrometry in the clinical laboratory: how have we done, and where do we
      need to be?

PMID- 19395434
TI  - Neopterin and cardiovascular disease: growing evidence for a role in patient risk
      stratification.

PMID- 19395435
TI  - Quality control and protein microarrays.

PMID- 19395437
TI  - False-negative results in point-of-care qualitative human chorionic gonadotropin
      (hCG) devices due to excess hCGbeta core fragment.
AB  - BACKGROUND: During pregnancy, human chorionic gonadotropin (hCG) immunoreactivity
      in urine consists of intact hCG as well as a number of hCG variants including the
      core fragment of hCGbeta (hCGbeta cf). We identified 3 urine specimens with
      apparent false-negative results using the OSOM(R) hCG Combo Test (Genzyme
      Diagnostics) qualitative hCG device and sought to determine whether an excess of
      1 of the fragments or variants might be the cause of the interference. METHODS:
      We measured concentrations of hCG variants in the urine from 3 patients with
      apparent false-negative hCG results. Purified hCG variants were added to urines
      positive for hCG and tested using the OSOM, ICON(R) 25 hCG (Beckman Coulter), and
      hCG Combo SP(R) Brand (Cardinal Health) devices. RESULTS: Dilution of these 3
      urine samples resulted in positive results on the OSOM device. Quantification of
      hCG variants in each of the 3 patient urine specimens demonstrated that hCGbeta
      cf occurred in molar excess of intact hCG. Addition of purified hCGbeta cf to hCG
      positive urines caused false-negative hCG results using the OSOM and ICON
      qualitative urine hCG devices. CONCLUSIONS: Increased concentrations of hCGbeta
      cf can cause false-negative results on the OSOM and ICON qualitative urine hCG
      devices.

PMID- 19395438
TI  - SELP and SELPLG genetic variation is associated with cell surface measures of
      SELP and SELPLG: the Atherosclerosis Risk in Communities Carotid MRI Study.
AB  - BACKGROUND: P-selectin (SELP) and its ligand, P-selectin glycoprotein ligand 1
      (SELPLG), play key roles in both the inflammatory response and the
      atherosclerotic process. Previous studies have shown genetic variation in the
      SELP gene [selectin P (granule membrane protein 140 kDa, antigen CD62)] to be
      associated with plasma SELP concentrations; however, the major biological
      function of SELP (and SELPLG) is at the cell surface. We therefore investigated
      the association of SELP polymorphisms with platelet SELP measures and
      polymorphisms in the SELPLG gene (selectin P ligand) with lymphocyte,
      granulocyte, and monocyte SELPLG measures among 1870 participants in the
      Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study. METHODS: Whole
      blood flow cytometry was used to analyze leukocyte and platelet markers in the
      ARIC Carotid MRI Study. The allele frequencies for the SELP and SELPLG
      polymorphisms of whites and African Americans were markedly different; therefore,
      all analyses were race specific. RESULTS: SELP T715P was significantly associated
      with lower values for platelet SELP measures in whites (P = 0.0001), whereas SELP
      N562D was significantly associated with higher values for SELP measures in
      African Americans (P = 0.02). SELPLG M62I was significantly associated with lower
      granulocyte and monocyte SELPLG measures in African Americans (P = 0.003 and P =
      0.0002, respectively) and with lower lymphocyte SELPLG measures in whites (P =
      0.01). CONCLUSIONS: Specific SELP and SELPLG polymorphisms were associated with
      cell surface measures of SELP and SELPLG in both whites and African Americans in
      the ARIC Carotid MRI Study. To our knowledge, this study is the first to examine
      the association of SELP and SELPLG genetic variation with measures of cell
      surface SELP and SELPLG.

PMID- 19395439
TI  - Neopterin as a predictor of total and cardiovascular mortality in individuals
      undergoing angiography in the Ludwigshafen Risk and Cardiovascular Health study.
AB  - BACKGROUND: Neopterin is produced upon activation of the cell-mediated immune
      response, and may be a novel risk marker for adverse outcomes resulting from
      coronary artery disease. METHODS: We measured neopterin in 1801 study
      participants with and 511 without angiographic coronary artery disease. Rates of
      death were determined after a median follow-up of 8.0 years. RESULTS: Estimated
      glomerular filtration rate and N-terminal pro-B-type natriuretic peptide (NT
      proBNP) were the strongest predictors of neopterin. Neopterin was positively
      related to age and inversely related to LDL cholesterol, HDL cholesterol, and
      triglycerides. Use of lipid-lowering drugs lowered neopterin. Sex, body mass
      index, diabetes mellitus, hypertension, smoking status, Friesinger coronary
      score, and clinical instability at presentation were not associated with
      neopterin. Unlike C-reactive protein, neopterin was not increased in unstable
      angina pectoris, non-ST-elevation myocardial infarction, or ST-elevation
      myocardial infarction. In the third and fourth quartiles of neopterin, unadjusted
      hazard ratios for death from any cause were 1.94 (95% CI 1.44-2.61) and 3.32 (95%
      CI 2.53-4.30) compared to individuals in the first quartile, whereas hazard
      ratios for death from cardiovascular causes were 2.14 (95% CI 1.44-3.18) and 3.84
      (95% CI 2.67-5.52), respectively. Neopterin remained predictive of total and
      cardiovascular mortality after adjusting for sex, age, body mass index, type 2
      diabetes, hypertension, smoking status, LDL cholesterol, HDL cholesterol,
      triglycerides, estimated glomerular filtration rate, NT-proBNP, and clinical
      status at presentation, but NT-proBNP substantially weakened this association.
      CONCLUSIONS: Neopterin is an independent predictor of all-cause and
      cardiovascular mortality in individuals with or without stable coronary artery
      disease.

PMID- 19395440
TI  - Comparison of LDL cholesterol concentrations by Friedewald calculation and direct
      measurement in relation to cardiovascular events in 27,331 women.
AB  - BACKGROUND: National Cholesterol Education Program (NCEP) guidelines recommend
      development of direct assays for LDL cholesterol (LDL-C) measurement, but it is
      unclear how these assays compare with Friedewald calculation in predicting
      cardiovascular disease (CVD). METHODS: In a study of 27 331 healthy women with
      triglycerides <or=4.52 mmol/L (<or=400 mg/dL), baseline fasting Friedewald LDL-C
      was compared with fasting and nonfasting direct homogenous measurement for
      incident CVD during an 11-year period. RESULTS: Fasting LDL-C measurements
      obtained by the 2 methods were highly correlated (r = 0.976, P < 0.001). Compared
      with fasting Friedewald LDL-C, mean fasting direct LDL-C was 0.15 mmol/L (5.6
      mg/dL) lower and nonfasting direct LDL-C 0.30 mmol/L (11.5 mg/dL) lower, both P <
      0.0001. The adjusted hazard ratio per 1-SD increment was 1.23 [95% CI 1.15-1.32;
      1-SD 0.88 mmol/L (34.1 mg/dL)] for fasting direct LDL-C and 1.22 [95% CI 1.14
      1.30; 1-SD 0.90 mmol/L (34.9 mg/dL)] for fasting Friedewald. Nonfasting LDL-C was
      not associated with CVD by either method. Fasting LDL-C measurements fell into
      the same NCEP risk category with either method for 79.3% of participants, whereas
      they differed by 1 NCEP category for 20.7% of participants, with most classified
      into a lower-risk category by direct LDL-C. CONCLUSIONS: The association of LDL-C
      with CVD by the 2 methods was nearly identical in fasting samples. However, the
      lower direct LDL-C concentrations may misclassify many individuals into a lower
      NCEP category. Moreover, the lack of association of nonfasting direct LDL-C with
      CVD raises questions regarding the clinical utility of a direct assay for LDL-C
      in nonfasting blood samples.

PMID- 19395441
TI  - Chronic diarrhea in a 5-year-old girl: pitfall in routine laboratory testing with
      potentially severe consequences.

PMID- 19395448
TI  - Lupus and cancer.
AB  - Individuals with systemic lupus erythematosus (SLE) have an increased
      susceptibility to certain types of cancer. Of particular concern are haematologic
      malignancies, specifically non-Hodgkin lymphoma, where a three- to four-fold
      increased risk is seen in SLE, compared with the general population. There is
      some evidence that immunosuppressive exposures play a role, although there appear
      to be other factors driving the risk. Lupus disease activity, with resultant
      dysregulated lymphocyte proliferation, may itself be a mediator of the
      association between SLE and lymphoma. Aside from haematologic malignancy risk,
      lung cancer also is increased in SLE compared with the general population, and
      smoking likely drives this risk in large part. Last but not least, cervical
      dysplasia is a concern in women with SLE, particularly with exposure to
      immunosuppressants; routine screening for this complication should not be
      neglected.

PMID- 19395447
TI  - The effects of apelin on hypothalamic-pituitary-adrenal axis neuroendocrine
      function are mediated through corticotrophin-releasing factor- and vasopressin
      dependent mechanisms.
AB  - The apelinergic system has a widespread expression in the central nervous system
      (CNS) including the paraventricular nucleus, supraoptic nucleus and median
      eminence, and isolated cells of the anterior lobe of the pituitary. This pattern
      of expression in hypothalamic nuclei known to contain corticotrophin-releasing
      factor (CRF) and vasopressin (AVP) and to co-ordinate endocrine responses to
      stress has generated interest in a role for apelin in the modulation of stress,
      perhaps via the regulation of hormone release from the pituitary. In this study,
      to determine whether apelin has a central role in the regulation of CRF and AVP
      neurones, we investigated the effect of i.c.v. administration of pGlu-apelin-13
      on neuroendocrine function in male mice pre-treated with the CRF receptor
      antagonist, alpha-helical CRF(9-41), and in mice-lacking functional AVP V1b
      receptors (V1bR KO). Administration of pGlu-apelin-13 (1 mg/kg i.c.v.) resulted
      in significant increases in plasma ACTH and corticosterone (CORT), which were
      significantly reduced by pre-treatment with alpha-helical CRF(9-41), indicating
      the involvement of a CRF-dependent mechanism. Additionally, pGlu-apelin-13
      mediated increases in both plasma ACTH and CORT were significantly attenuated in
      V1bR KO animals when compared with wild-type controls, indicating a role for the
      vasopressinergic system in the regulation of the effects of apelin on
      neuroendocrine function. Together, these data confirm that the in vivo effects of
      apelin on hypothalamic-pituitary-adrenal neuroendocrine function appear to be
      mediated through both CRF- and AVP-dependent mechanisms.

PMID- 19395449
TI  - Fulminant leucocytoclastic brainstem vasculitis in a patient with otherwise
      indolent systemic lupus erythematosus.
AB  - The spectrum of central nervous system (CNS) vascular pathology in systemic lupus
      erythematosus (SLE) includes small vessel vasculopathy, thromboembolism,
      perivascular lymphocytic infiltration and, rarely, overt transmural vasculitis.
      We present the case of a patient, who experienced three CNS relapses over total
      disease duration of 26 years, with otherwise indolent disease. The first two
      relapses were suspicious of vasculitis and the last was proven at autopsy. The
      short duration between final relapse onset and death in this SLE CNS vasculitis
      case was, to our knowledge, unique. Histopathological investigation demonstrated
      multiple confluent areas of haemorrhage in the medulla due to an acute small
      vessel leucocytoclastic vasculitis.

PMID- 19395450
TI  - Onset of autoimmune glomerulonephritis derived from the telomeric region of MRL
      chromosome 1 is associated with the male sex hormone in mice.
AB  - Female B6.MRLc1(82-100) congenic mice develop more severe autoimmune
      glomerulonephritis (AGN) than males. We assessed the effects of gonadectomy on
      the pathogenesis of AGN in these mice. One-month-old male and female mice were
      divided into sham-operated group (SG) and gonadectomized group (GG), and the
      pathological changes were investigated at 8 months. SG females showed higher
      spleen and thymus weights, serum total IgG and autoantibody levels, glomerular
      damage scores and percent IgG- and CD3-positive glomeruli as compared with SG
      males. Gonadectomy showed more remarkable effects in males than in females.
      Spleen and thymus weights, urinary albumin excretion, glomerular damage scores,
      percent IgG- and CD3-positive glomeruli, and CD3-positive areas in the spleen
      were significantly higher in GG males than in SG males. CD3-positive cells were
      observed in both the thymic cortex and medulla in all animals except SG males.
      The expression ratio of active Fc gamma receptor (Fcgr) 3 to inhibitory Fcgr2b in
      the kidneys, which we have previously demonstrated to have a great impact on
      pathogenesis in B6.MRLc1(82-100), was significantly higher in GG males than in SG
      males. These results suggested that the differences in the pathogenesis of AGN
      are primarily because of the inhibitory roles of the male sex hormones.

PMID- 19395451
TI  - Increased expression of soluble inducible costimulator ligand (ICOSL) in patients
      with systemic lupus erythematosus.
AB  - To investigate the level of costimulating molecules in systemic lupus
      erythematosus (SLE), we assessed the plasma concentrations of soluble forms of
      costimulatory molecules such as programmed death-1 (PD-1), B7-H1 (also called PD
      L1 or CD274) and inducible costimulator ligand (ICOSL) in patients with SLE.
      Plasma concentrations of soluble PD-1, B7-H1 and ICOSL were measured by ELISA
      using plasma samples from 57 SLE patients with or without the active disease, 21
      rheumatoid arthritis (RA) patients and 35 healthy subjects. We also evaluated
      surface ICOSL expression on B cells using flow cytometry to gain a better
      understanding of ICOSL expression. To compare the level of ICOSL mRNA expression,
      reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using
      total RNA from peripheral blood mononuclear cells (PBMCs) isolated from eight
      healthy subjects and 11 patients with SLE. The concentration of plasma ICOSL was
      significantly higher in patients with SLE compared with healthy subjects (P =
      0.005). Plasma ICOSL concentrations in patients with active SLE were also
      significantly higher than those of either patients with inactive SLE or patients
      with RA (P = 0.001, P = 0.015, respectively). Plasma ICOSL concentrations in
      patients with SLE correlated modestly with the SLE disease activity index score
      (r = 0.298, P = 0.024). We also found a significant inverse correlation between
      the soluble ICOSL expression and the surface ICOSL expression on B cells (r = 
      0.690, P = 0.001). However, ICOSL mRNA levels of patients with SLE were
      comparable with those of the control subjects. There was also no significant
      difference in plasma B7-H1 concentrations between groups, and plasma PD-1 was not
      detectable in any of the groups. The plasma concentration of soluble ICOSL might
      be correlated to the disease severity of lupus. The increased levels of ICOSL in
      active lupus suggest that this pathway is involved in the pathogenesis of SLE.
      The mechanism and physiological role of soluble ICOSL in the pathogenesis of SLE,
      however, remains to be investigated.

PMID- 19395452
TI  - Prevalence, predictors and outcome of vascular damage in systemic lupus
      erythematosus.
AB  - Despite improved prognosis, patients with systemic lupus erythematosus (SLE)
      remain at increased risk for early death. Vascular events (VE) occur with
      increased frequency and contribute to premature death in SLE patients. As
      conventional cardiovascular risk factors do not fully explain this hazard, this
      study investigated the contribution of disease-specific features to VE
      development. Documented VE were classified as atherothrombotic, venous
      thrombotic, arterial thrombotic or tissue loss inducing vasculitis during a mean
      follow-up of nearly 12 years in the Tromso Lupus cohort (n = 158). The impact of
      disease-specific factors (organ manifestations, laboratory findings, drug
      treatment, weighted average SLE Disease Activity Index (WAS) and cumulative
      Damage Index) was assessed by odds ratios for VE in multivariate analysis. A
      total of 41 patients (26%) developed VE, and atherothrombotic events were most
      common (73%). Overall, VE prevalence was 3.5/100 patient years, and VE risk
      increased linearly over time, reaching 35% after 20 years. WAS scores >3
      increased, and use of hydroxychloroquine and antihypertensive medication reduced
      overall VE risk. Age >40 years was the main risk factor for atherothrombotic
      events. VE nearly quadrupled the risk of death. VE occurred in 26% of SLE
      patients, predominantly as atherothrombotic disease. VE prevalence increased
      linearly over time leading to a four-fold risk of mortality. Strategies for
      reducing disease activity, including treatment with antimalarials and
      antihypertensive drugs, are most likely to reduce the risk associated with VE in
      SLE.

PMID- 19395453
TI  - Does mycophenolate mofetil prevent extra-renal flares in systemic lupus
      erythematosus? Results from an observational study of patients in a single
      practice treated for up to 5 years.
AB  - In this study, the clinical course and change in extra-renal manifestations of
      patients with SLE taking mycophenolate mofetil (MMF) were evaluated. The charts
      of 75 consecutively identified patients on MMF from a single practice were
      reviewed for demographics, dates of SLE diagnosis, initiation, indication or
      discontinuation of MMF and other medications. British Isles Lupus Assessment
      Group (BILAG) organ system data were identified for 3 months prior to MMF and
      then for the subsequent 5 years. BILAG scores for each organ system and an
      overall score were calculated for intervals of 6 months. The mean age of 75
      subjects was 35.8 years with SLE mean disease duration of 99.2 months.
      Indications for starting MMF were renal (70.7%), musculoskeletal (10.6%),
      mucocutaneous (9.3%), cardiorespiratory (5.3%), haematologic (4%), vasculitic
      (2.7%), neurologic (1.3%) and other (18.7%). The mean duration of treatment was
      3.3 years; 22 discontinuations occurred. Overall, there was a >50% improvement in
      composite BILAG scores for 49.3% (37/75) of patients in the first year of
      treatment and in 20% (15/75) of patients who were still on MMF at >or=5 years.
      Most flares occurred at second and third year of treatment. The general and renal
      systems have the most improvement and clinical remissions; the musculoskeletal,
      mucocutaneous and haematological systems have the most recurrences.
      Approximately, 50% and 20% of patients taking MMF showed improvement in overall
      lupus disease activity at both 1 and 5 years, respectively. When evaluating organ
      system subsets separately, MMF improved disease activity in the first year, but
      had little effect in preventing new organ-specific flares, with most flares
      taking place in second and third year of treatment.

PMID- 19395454
TI  - Arterial wall dysfunction in systemic lupus erythematosus.
AB  - Carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and
      endothelium-dependent flow-mediated dilatation (FMD) have been repeatedly showed
      to be related to premature atherosclerosis and cardiovascular diseases in
      different settings of population. The increased arterial stiffness and
      endothelium dysfunction may add to premature aging of the arteries in systemic
      lupus erythematosus (SLE) patients. Still data about arterial stiffness and
      endothelium function in inflammatory rheumatic diseases are not well described.
      The aim of this study was to determine the PWV, its derivate marker AIx and FMD
      and factors possibly influencing them in young SLE women without significant
      organ damage. Thirty women between 23 and 55 years with an established SLE
      diagnosis and 66 healthy women were consequently included in the study and both
      groups were comparable according to age, body mass index (BMI), serum lipid
      profile and creatinine. PWV was determined by measuring carotid-radial pulse wave
      transit time with the help of applanation tonometry and AIx, its derivate marker,
      was calculated as a difference between two waveform peaks expressed as a
      percentage of the pulse pressure. The FMD was performed by obtaining the repeated
      scans of the brachial artery at rest and during reactive hyperemia. In SLE women,
      PWV and AIx were significantly higher and FMD was not different from controls. In
      linear multiple stepwise regression analysis if patients and controls were both
      considered, PWV was weakly related to mean blood pressure (MBP), AIx was mostly
      predicted by age and MBP and FMD was predicted by the diameter of blood vessel,
      BMI, high density lipoproteins. If the sole SLE setting was analyzed, PWV was not
      related to any of the pending parameters, AIx turned out to be related to organ
      damage measured by Systemic Lupus International collaborative Clinics (SLICC)
      index and age, and FMD obtained strong and significant relation with vessel
      diameter, and BMI, and disease duration. Regardless of the small number of study
      group patients, we can state that controlling for MBP and taking measures towards
      organ damage prevention can partially slow down the process of early
      atherosclerosis in SLE patients.

PMID- 19395455
TI  - Serum complement activation on heterologous platelets is associated with arterial
      thrombosis in patients with systemic lupus erythematosus and antiphospholipid
      antibodies.
AB  - Complement plays a major role in inflammation and thrombosis associated with
      systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). A
      cross-sectional retrospective analysis was performed to evaluate serum complement
      fixation on platelets and thrombotic incidence using banked sera and clinical
      data from patients with SLE (n = 91), SLE with antiphospholipid antibodies (aPL)
      or APS (n = 78) and primary aPL (n = 57) or APS (n = 96). In-situ complement
      fixation was measured as C1q and C4d deposition on heterologous platelets using
      an enzyme-linked immunosorbent assay approach. Platelet activation by patient
      serum in the fluid phase was assessed via serotonin release assay. Enhanced in
      situ complement fixation was associated with the presence of IgG aPL and IgG anti
      beta2 glycoprotein 1 antibodies (P < 0.05) and increased platelet activation (P <
      0.005). Moreover, enhanced complement fixation, especially C4d deposition on
      heterologous platelets, was positively associated with arterial thrombotic events
      in patients with SLE and aPL (P = 0.039). Sera from patients with aPL possess an
      enhanced capacity for in-situ complement fixation on platelets. This capacity may
      influence arterial thrombosis risk in patients with SLE.

PMID- 19395456
TI  - Autoantibodies against galectin-8: their specificity, association with
      lymphopenia in systemic lupus erythematosus and detection in rheumatoid arthritis
      and acute inflammation.
AB  - The role of autoantibodies in the pathogenesis of systemic lupus erythematosus
      (SLE) has not been completely defined. From more than a hundred autoantibodies
      described in SLE, relatively few have been associated with clinical
      manifestations. The glycan-binding proteins of the galectin family can modulate
      the immune system. Anti-galectin autoantibodies thus could have functional and/or
      pathogenic implications in inflammatory processes and autoimmunity. We previously
      reported function-blocking autoantibodies against galectin-8 (Gal-8) in SLE. Here
      we tested these autoantibodies against a series of other human galectins and
      demonstrated their specificity for Gal-8, being detectable in 23% of 78 SLE
      patients. Remarkably, they associated with lymphopenia (50% of 18 anti-Gal-8
      positive versus 18% of 60 anti-Gal-8-negative cases, Fisher's Exact test two
      tailed: P < 0.012). Lymphopenia is a common clinical manifestation in SLE, yet of
      unknown mechanism. In addition, six of eight patients with both lymphopenia and
      malar rash had anti-Gal-8 in their sera. Occurrence of these autoantibodies was
      not confined to SLE as we also found them in sera of patients with rheumatoid
      arthritis (16%) and septicemia (20%). This study thus establishes occurrence of
      specific anti-Gal-8 autoantibodies in autoimmune rheumatic diseases and in acute
      inflammation, with an apparent association to a clinical subset in SLE.

PMID- 19395457
TI  - An exploratory dose-escalating study investigating the safety, tolerability,
      pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with
      systemic lupus erythematosus.
AB  - Atacicept, a recombinant fusion protein containing the extracellular, ligand
      binding portion of the transmembrane activator and calcium modulator and
      cyclophilin-ligand interactor receptor, and the Fc portion of human
      immunoglobulin (Ig) G, is designed to block the activity of B-lymphocyte
      stimulator and a proliferation-inducing ligand, and may have utility as a
      treatment for B-cell-mediated diseases, such as systemic lupus erythematosus
      (SLE). This Phase Ib study investigated the safety, tolerability,
      pharmacokinetics (PK) and pharmacodynamics of intravenous (i.v.) atacicept in
      patients with mild-to-moderate SLE. Patients (n = 24) were randomised (5:1) to
      receive atacicept (single dose: 3, 9 or 18 mg/kg; or multiple dose: 2 x 9 mg/kg)
      or matching placebo. Patients were followed for 6 weeks after dosing (9 weeks in
      the 2 x 9 mg/kg cohort). Local tolerability of atacicept was comparable with that
      of placebo, with only mild injection-site reactions reported with atacicept.
      Atacicept i.v. was generally well tolerated, both systemically and locally, in
      patients with mild-to-moderate SLE. Atacicept displayed non-linear PK, which was
      predictable across doses and between single and repeat doses. The biological
      activity of atacicept was demonstrated by its marked effect in reducing B-cells
      and Ig levels in patients with SLE. This supports the utility of this therapeutic
      approach in the treatment of autoimmune diseases, such as SLE.

PMID- 19395458
TI  - Ultraviolet light output of compact fluorescent lamps: comparison to conventional
      incandescent and halogen residential lighting sources.
AB  - Patients with photosensitive dermatologic and systemic diseases often question
      the ultraviolet light (UVL) output of household lighting sources. Such
      individuals have increasing concern about potential UVL exposure from energy
      efficient compact fluorescent lamps (CFL), as little data have been presented
      concerning their UVL output. The objective was to compare, via pilot study, the
      levels of ultraviolet A (UVA) and ultraviolet B (UVB) leak between residential
      lighting sources. Equivalent wattage CFL, incandescent and halogen bulbs were
      purchased from local retailers in Oklahoma City, Oklahoma, USA. The UVA and UVB
      outputs of these sources were measured under controlled conditions at 10, 25, 50,
      100 and 150 cm away from the light source using an IL-1700 research radiometer
      equipped with UVA and UVB detectors. Negligible UVB and UVA was detected at 100
      and 150 cm. Therefore, data were analysed from measurements at 10, 25 and 50 cm
      only. The results demonstrated UVA leak highest from incandescent and halogen
      bulbs, and UVB leak highest from CFL. The overall UVA/UVB leak was lowest from
      CFL shielded during the manufacturing process. In conclusion, patients with
      photosensitivity have choices depending on their relative risk from different UVL
      wavelength spectra. UVB exposure risk may be reduced the greatest by utilising
      CFL with manufacturer-provided shields.

PMID- 19395459
TI  - Acute acalculous cholecystitis in juvenile systemic lupus erythematosus.
AB  - Small- and medium-vessel vasculitis is a common manifestation in systemic lupus
      erythematosus (SLE) and may occur in any organ. However, acute acalculous
      cholecystitis is a rare abdominal manifestation in SLE, especially in children.
      We report a case of a 12-year-old patient who initially presented with AAC and
      seizure. Follow-up investigation diagnosed SLE, and brain magnetic resonance
      imaging had hyperintense white matter lesions in cortico-subcortical regions. The
      patient was successfully treated with pulse methylprednisolone and
      cyclophosphamide without surgical intervention.

PMID- 19395460
TI  - Twenty-year follow-up: an unusual case of nephropathy of antiphospholipid
      syndrome.
AB  - Nephropathy of antiphospholipid antibody syndrome (NAPS) is an increasingly well
      recognized aspect of antiphospholipid syndrome. The most characteristic
      histopathology is that of thrombotic microangiopathy, and thrombosis occurring in
      the renal vasculature is thought to be the initiating event. Other less common
      pathologies have been reported, and the mechanisms of these are unclear. Therapy
      has been largely empiric. We report a case of NAPS in a patient with atypical
      pathology, who has declined therapy with immunosuppressive agents and
      anticoagulants and who has maintained normal renal function in 20 years of follow
      up.

PMID- 19395461
TI  - Renal limited Wegener's granulomatosis.
AB  - Differential diagnosis in patients presenting with fever of unknown origin (FUO)
      is often difficult because infectious diseases, neoplasms, infective endocarditis
      or systemic autoimmune diseases may all be responsible for the condition.
      Furthermore, vasculitis may generate typical, atypical or limited syndromes
      depending on the extent of vascular involvement. Here, we report the case of a 73
      year-old man with FUO and renal failure due to a rare variant of Wegener's
      granulomatosis, limited to the kidneys.

PMID- 19395462
TI  - Splenic microcalcifications in systemic lupus erythematosus.

PMID- 19395463
TI  - Risk stratification of high-grade prostate cancer treated with antegrade radical
      prostatectomy with intended wide resection.
AB  - OBJECTIVE: The aim of this study was to assess the surgical outcome of high-grade
      prostate cancer (PCA) treated with antegrade radical prostatectomy with intended
      wide resection (aRP) and to establish the risk stratification. METHODS: A
      consecutive 77 Japanese patients with Gleason score 8-10 PCA were treated with
      aRP alone and excluding patients with persistently elevated prostate-specific
      antigen (PSA), prospectively observed without any treatment until PSA failure was
      confirmed. PSA failure-free, cancer-specific and overall survival curves were
      generated with Kaplan-Meier method and the difference between groups was assessed
      with log-rank test. Cox's proportional hazards model was used to elucidate
      predictors of PSA failure. RESULTS: During a median follow-up of 6 years, PSA
      failure was observed in 41 (53%) of the 77 patients. Five- and 10-year PSA
      failure-free survival rates of the entire cohort were 44.6% and 40.1%,
      respectively. Both overall and cancer-specific survival rates of the entire
      cohort at 5 and 10 years were 96.8% and 87.9%, respectively. In a multivariate
      analysis, PSA (P = 0.008), specimen confinement (SC) (P = 0.006) and persistently
      elevated PSA after aRP were identified as significant and independent predictors
      of PSA failure. When stratifying patients into three risk groups according to PSA
      level and SC status, PSA failure-free survival rate in patients with PSA < 10
      ng/ml and specimen-confined disease (SCD) was significantly better than that in
      those of any other groups. CONCLUSIONS: Good prognosis can be expected in
      patients with high-grade PCA treated with aRP alone when PSA < 10 ng/ml and the
      tumor was removed as an SCD.

PMID- 19395464
TI  - NF-kappaB activation through the alternative pathway correlates with
      chemoresistance and poor survival in extranodal NK/T-cell lymphoma, nasal type.
AB  - OBJECTIVE: Nuclear factor-kappaB (NF-kappaB) activation has been identified in a
      variety of solid tumors and lymphoid malignancies. The aim of our study was to
      determine the expression status and clinical significance of NF-kappaB in
      extranodal natural killer (NK)/T-cell lymphoma, nasal type. METHODS: Tumor
      specimens from 23 patients with previously untreated NK/T-cell lymphoma initially
      treated with cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP) or
      CHOP-based chemotherapy were examined by immunohistochemistry for three NF-kappaB
      subunits (p65, p50 and p52), which are involved in either the canonical or
      alternative pathway. RESULTS: None of the cases could be detected with p65 or p50
      nuclear staining. On the other hand, 15 (65.2%) cases had p52 nuclear staining,
      suggesting NF-kappaB activation through the alternative pathway. All major
      clinical characteristics were balanced between NF-kappaB p52-positive and 
      negative patients. The objective response rate achieved in NF-kappaB-positive
      patients was significantly lower than that in negative patients (33.3% vs. 87.5%,
      P = 0.027). At a median follow-up of 25 months, 8 (53.3%) of 15 NF-kappaB
      positive patients had died compared with none of 8 NF-kappaB-negative patients (P
      = 0.041). In a multivariate analysis, NF-kappaB status and stage were identified
      to be independent prognostic factors. CONCLUSIONS: Our results suggest that NF
      kappaB activation through the alternative pathway is frequently observed in NK/T
      cell lymphoma and associated with chemoresistance and poor survival.

PMID- 19395465
TI  - Relapse with malignant transformation after chemotherapy for primary mediastinal
      seminoma: case report.
AB  - This case report details a relapse with malignant transformation after the
      completion of bleomycin, etoposide and cisplatin chemotherapy for primary
      mediastinal seminoma, although the residual mass after chemotherapy was <3 cm in
      size and did not display an increased uptake of fluorodeoxyglucose when examined
      using positron emission tomography.

PMID- 19395466
TI  - Randomized controlled study comparing two doses of intravenous granisetron (1 and
      3 mg) for acute chemotherapy-induced nausea and vomiting in cancer patients: a
      non-inferiority trial.
AB  - OBJECTIVE: The aim of this study was to assess the non-inferiority of 1 mg to 3
      mg granisetron (GRN) injection for the treatment of acute chemotherapy-induced
      nausea and vomiting (CINV) and to evaluate the tolerability of GRN given at 1 mg
      in Japanese cancer patients. METHODS: Patients with cancer receiving highly
      emetogenic chemotherapy were enrolled in this single-blind randomized controlled
      study. Patients were randomly assigned to receive GRN at a single dose of 1 or 3
      mg. The primary endpoint was the rate of complete protection from emetic events
      (no vomiting, no retching and no need for rescue medication) during the first 24
      h following the initiation of chemotherapy. RESULTS: There were 89 patients in
      the 1 mg group and 90 patients in the 3 mg group. Complete protection was
      achieved in 70 patients (78.7%) in the 1 mg group and 73 (81.1%) patients in the
      3 mg group. The one-sided test did not reveal non-inferiority of either dose of
      GRN to the other at a 5% significance level. CONCLUSIONS: Our data failed to show
      the non-inferiority of 1 mg of GRN to 3 mg of GRN administered as a single dose.
      However, the rate of complete protection from nausea and vomiting was similar in
      the two groups. Given the recommended dosage in the guidelines and the economic
      need for reduction of medical care expenses in Japan, prophylactic administration
      of GRN at 1 mg may be an appropriate, alternative treatment for acute CINV in
      cancer patients.

PMID- 19395467
TI  - A pharmacokinetic and dose escalation study of pegfilgrastim (KRN125) in lung
      cancer patients with chemotherapy-induced neutropenia.
AB  - OBJECTIVE: The aim of this study was to investigate the safety, pharmacokinetic
      and pharmacodynamic profiles of pegfilgrastim (KRN125), a long-acting granulocyte
      colony-stimulating factor, in lung cancer patients with chemotherapy-induced
      neutropenia. METHODS: Eighteen Japanese lung cancer patients who had experienced
      severe neutropenia (absolute neutrophil counts <0.5 x 10(9) cells/l) were
      enrolled. Six patients were sequentially enrolled in each pegfilgrastim dose
      cohort (dose levels of 30, 60 or 100 microg/kg). Patients received the same
      chemotherapy regimen as in their previous cycle and pegfilgrastim was injected
      subcutaneously the day after chemotherapy ended in each treatment cycle.
      Pharmacokinetic, pharmacodynamic and safety analyses were performed. RESULTS:
      Dose-limiting toxicity and serious adverse events related to pegfilgrastim were
      not observed in any patients. Pegfilgrastim antibodies were not detected. Maximum
      serum concentrations and area under the serum concentration-time curves of
      pegfilgrastim were dependent on the pegfilgrastim dose in a non-linear manner. Of
      the 18 patients, severe neutropenia occurred in 4 (22.2%), and, of these, 1
      patient (5.5%) required rescue treatment by filgrastim. CONCLUSIONS: A single
      dose of pegfilgrastim increases the serum concentration of pegfilgrastim for
      several days in a dose-dependent manner and is not associated with significant
      toxicity. Good efficacy of pegfilgrastim for the prevention of severe neutropenia
      was observed at all dose levels. Based on these data, further studies are
      warranted to determine the recommended dose of pegfilgrastim for Japanese
      patients with chemotherapy-induced neutropenia.

PMID- 19395468
TI  - A comprehensive comparative study on the characteristics of colorectal cancer
      chemotherapy.
AB  - OBJECTIVE: Analyses were performed to assess whether the use of chemotherapeutic
      agents or regimens against colorectal cancer (CRC) differed among countries,
      especially the United States (USA), the European Union (EU) and Japan. METHODS:
      The data source for this study was the IMS Health, Oncology Analyzer. We utilized
      data on the use of anticancer drugs and follow-up information for patients with
      CRC from April 2006 to March 2007, collected from the USA, the EU (G5: France,
      Germany, Italy, Spain and the UK) and Japan. A total of 102 502 patients were
      enrolled. RESULTS: Wide differences were found in the actual regimens adopted by
      each region and nation. In other words, the concept of oncologist-related
      variability in chemotherapy for CRC was clearly seen. Factors such as a nation's
      historical characteristics and the healthcare policies of respective governments,
      including drug approval and cost-effectiveness, also appeared to have roles.
      However, comparisons of 5-year relative survival rates from population-based
      cancer registries in the USA, the EU and Japan showed that survival rates for CRC
      in the three regions did not differ widely, despite differences in the actual use
      of medical therapy. This may suggest that regional usage trends for anticancer
      regimens were optimal, although the application of chemotherapy was not the
      intentional standardization. CONCLUSIONS: Global information exchanges regarding
      oncologist-related factors along with global evidence could result in patient
      survival being prolonged by the establishment of intentional standardized
      treatments suited for regional characteristics.

PMID- 19395469
TI  - Application of patient safety indicators internationally: a pilot study among
      seven countries.
AB  - OBJECTIVE: To explore the potential for international comparison of patient
      safety as part of the Health Care Quality Indicators project of the Organization
      for Economic Co-operation and Development (OECD) by evaluating patient safety
      indicators originally published by the US Agency for Healthcare Research and
      Quality (AHRQ). DESIGN: A retrospective cross-sectional study. SETTING: Acute
      care hospitals in the USA, UK, Sweden, Spain, Germany, Canada and Australia in
      2004 and 2005/2006. DATA SOURCES: Routine hospitalization-related administrative
      data from seven countries were analyzed. Using algorithms adapted to the
      diagnosis and procedure coding systems in place in each country, authorities in
      each of the participating countries reported summaries of the distribution of
      hospital-level and overall (national) rates for each AHRQ Patient Safety
      Indicator to the OECD project secretariat. RESULTS: Each country's vector of
      national indicator rates and the vector of American patient safety indicators
      rates published by AHRQ (and re-estimated as part of this study) were highly
      correlated (0.821-0.966). However, there was substantial systematic variation in
      rates across countries. CONCLUSIONS: This pilot study reveals that AHRQ Patient
      Safety Indicators can be applied to international hospital data. However, the
      analyses suggest that certain indicators (e.g. 'birth trauma', 'complications of
      anesthesia') may be too unreliable for international comparisons. Data quality
      varies across countries; undercoding may be a systematic problem in some
      countries. Efforts at international harmonization of hospital discharge data sets
      as well as improved accuracy of documentation should facilitate future
      comparative analyses of routine databases.

PMID- 19395470
TI  - Prevention of adhesions in surgery of the flexor tendons of the hand: what is the
      evidence?
AB  - INTRODUCTION: Despite advances in knowledge and refinements of technique, the
      management of flexor tendon injuries within the digital sheath continues to
      present a formidable challenge. This in turn has led to a massive expansion in
      search of modified surgical therapies and various adjuvant therapies, which could
      prevent adhesion formation without compromising digital function. SOURCES OF
      DATA: A search of PubMed, Medline, CINAHL and Embase databases was performed
      using the keywords 'tendon adhesion prevention', 'tendon healing', 'adhesion
      prevention in tendons' and 'adjuvants for adhesion prevention'. Studies detailing
      the use of surgical, pharmacological and non-pharmacological agents for adhesion
      prevention in digital flexor tendons were identified, and their bibliographies
      were thoroughly reviewed to identify further related articles. This search
      identified 41 studies, which investigated the use of various pharmacological
      agents in adhesion prevention in digital tendons. AREAS OF AGREEMENT: There is a
      need to develop and utilize an optimal method for the prevention of adhesions in
      the flexor tendons of the hand, due to post-surgical complications. AREAS OF
      CONTROVERSY: Even though there have been significant advances in the prevention
      of adhesions in flexor tendons, it remains to be proved which, if any, of the
      current methods are the most beneficial. GROWING POINTS: The only thing that
      appears clinically justified in adhesion prevention is the need for early post
      operative mobilization of digits after tendon injury or repair but the best
      method of mobilization remains controversial. AREAS TIMELY FOR DEVELOPING
      RESEARCH: Suggested changes in surgical techniques and various proposed
      pharmacological and non-pharmacological modalities need to withstand the test of
      adequately powered human trials, before their justification for potential benefit
      in clinical practice is accepted.

PMID- 19395471
TI  - Immune-based therapy for chronic hepatitis C.
AB  - Chronic, persistent HCV infection is a public health issue. It often progresses
      to life-threatening complications, including liver cirrhosis and hepatocellular
      carcinoma. The current standard therapy is a combination of pegylated IFN-alpha
      and ribavirin. This therapy results in a sustained virologic response in only 50%
      of patients infected with HCV genotype 1 and is often accompanied with
      substantial side-effects. Therefore, it is imperative to develop novel therapies
      with higher efficacy and less substantial side-effects. Impaired immune responses
      to HCV are key features of chronic HCV infection; thus, intervention strategies
      typically involve boosting the immune responses against HCV. These immune-based
      therapies for chronic HCV infection include therapeutic vaccines, antagonists of
      T cell inhibitory factors, anti-HCV neutralizing antibodies, cytokines, and
      agonists for TLRs. Currently, various types of immune-based therapies are under
      development that might be used as a monotherapy or in combination with other
      antiviral drugs for the treatment of chronic HCV infection.

PMID- 19395473
TI  - Polyethylene glycosylated curcumin conjugate inhibits pancreatic cancer cell
      growth through inactivation of Jab1.
AB  - Jab1 (Jun activation domain binding protein 1), integrated into COP9 signalosome
      complex (CSN), induces protein instability of many tumor suppressors and cell
      cycle regulators and is therefore a novel target in cancer therapy. Curcumin, an
      inhibitor of Jab1/CSN-associated kinase(s), has been reported to suppress tumor
      growth; however, curcumin is highly hydrophobic, and this feature prevents its
      usage as an antitumor drug. To increase the solubility and targeted delivery, we
      generated a water-soluble polyethylene glycol (PEG)-conjugated curcumin system,
      in which curcumin is covalently linked to PEG(35kD). PEGylated curcumin showed
      much greater reduction of cell growth than free curcumin in pancreatic cancer
      cells. Cells treated with PEGylated curcumin had increased arrest at the mitotic
      phase with the formation of abnormal multinucleated cells, indicating that this
      compound affects cell cycle progression, which may contribute to cell growth
      inhibition. The stabilities of Jab1 target proteins were also examined. PEGylated
      curcumin increased protein stability of these proteins in pancreatic cancer cells
      and directly inhibited the activity of Jab1/CSN-associated kinases. Moreover, the
      inhibitory effect of PEGylated curcumin on cell proliferation was blunted in
      pancreatic cancer cells with Jab1 knockdown. The results suggest that PEGylated
      curcumin inhibits cell proliferation through suppression of Jab1/CSN activity.
      More importantly, the new compound sensitized pancreatic cancer cells to
      gemcitabine-induced apoptosis and cell proliferation inhibitory effects.
      Collectively, the PEGylated curcumin conjugate has much more potent effects on
      pancreatic cancer cell growth inhibition than free curcumin. The current study
      provides a biologic rationale to treat patients with pancreatic adenocarcinoma
      with the nontoxic phytochemical conjugated to PEG for systemic delivery.

PMID- 19395472
TI  - Hemopexin down-regulates LPS-induced proinflammatory cytokines from macrophages.
AB  - Detection of LPS in tissues is an integral component of innate immunity that acts
      to protect against invasion by Gram-negative bacteria. Plasma down-regulates LPS
      induced cytokine production from macrophages, thereby limiting systemic
      inflammation in blood and distant tissues. To identify the protein(s) involved in
      this process, we used classical biochemical chromatographic techniques to
      identify fractions of mouse sera that suppress LPS-induced TNF from bone marrow
      derived macrophages (BMDMs). Fractionation yielded microgram quantities of a
      protein that was identified by MS to be hemopexin (Hx). Mouse Hx purified on
      hemin-agarose beads and rhHx decreased the production of cytokines from BMDMs and
      peritoneal macrophages induced by LPS. Preincubation of LPS with Hx did not
      affect the activity of LPS on LAL, whereas preincubation of Hx with macrophages
      followed by washing resulted in decreased activity of these cells in response to
      LPS, suggesting that Hx acts on macrophages rather than LPS. Heme-free Hx did not
      stimulate HO-1 in the macrophages. Purified Hx also decreased TNF and IL-6 from
      macrophages induced by the synthetic TLR2 agonist Pam3Cys. Our data suggest that
      Hx, which is an acute-phase protein that increases during inflammation, limits
      TLR4 and TLR2 agonist-induced macrophage cytokine production directly through a
      mechanism distinct from HO-1.

PMID- 19395474
TI  - Magic-angle phosphorus NMR of functional mitochondria: in situ monitoring of
      lipid response under apoptotic-like stress.
AB  - Using a noninvasive, solid-state magic-angle spinning nuclear magnetic resonance
      (MAS NMR) approach, we track ex vivo the behavior of individual membrane
      components in isolated, active mitochondria (model system: potato tubers) during
      physiological processes. The individual phosphatidylcholine (PC),
      phosphatidylethanolamine (PE), and cardiolipin (CL) membrane constituents were
      identified as distinct lines by applying MAS (31)P NMR on extracted lipid
      membranes. However, the CL NMR signal appeared to be very broad in functional
      mitochondria, indicating a tight complex formation with membrane protein. Calcium
      stress induced severe membrane degradation without recovery of a single CL NMR
      resonance. This suggests that calcium overload destroys the outer mitochondrial
      membrane and does not modify strongly the CL protein complexes in the inner
      membrane; a conclusion confirmed by respiratory controls. Conversely,
      mitochondrial membrane disruption on time degradation or mechanical stress
      generates clearly visible identical CL NMR signals, similar to those observed in
      rehydrated lipid extracts. Similarly, noninvasive based NMR tracking of lipids in
      response to diverse physiological stimuli can easily be used for other organelles
      and whole living cells.

PMID- 19395475
TI  - Multifunctional protein nanocarriers for targeted nuclear gene delivery in
      nondividing cells.
AB  - Compartmentalization within eukaryotic cells hinders the efficient delivery of
      therapeutic agents to the cell nucleus. Here we describe novel multifunctional
      DNA carriers (MDCs) that self-assemble with DNA to form structured nanoparticles
      that possess virus-like functions for cellular trafficking. MDCs contain, in
      fusion, the DNA-compacting sperm chromatin component protamine, alpha-melanocyte
      stimulating hormone for cell-targeted internalization, the endosome-translocation
      domain of diphtheria toxin, and an optimized nuclear localization sequence to
      confer recognition by the nuclear import machinery. The structure of the MDC-DNA
      particles was examined using atomic force microscopy, and the functionality of
      each domain assessed using in vitro techniques, including a reconstituted nuclear
      transport assay in semi-intact cells relying on the use of quantitative confocal
      laser scanning microscopy. The nanoparticles were internalized in cell-specific
      fashion and subsequently exited the endosome into the cytoplasm. Notably, the
      nanoparticles interact with cellular nuclear transport proteins as shown in
      direct binding assays and are actively trafficked into the cell nucleus of
      nondividing cells, resulting in 3- to 4-fold higher reporter gene expression in
      growth-arrested human embryonic kidney cells, as well as lower cytotoxicity, than
      lipid and polyethyleneimine vectors. The importance of each functional domain was
      examined by comparing MDCs with different domain compositions as controls, as
      well as using antibodies to block particular pathways. MDCs that utilize cellular
      signaling pathways have enormous potential to safely and efficiently deliver
      therapeutic transgenes into the nucleus of nondividing cells.

PMID- 19395476
TI  - Indolyl-quinuclidinols inhibit ENOX activity and endothelial cell morphogenesis
      while enhancing radiation-mediated control of tumor vasculature.
AB  - There is a need for novel strategies that target tumor vasculature, specifically
      those that synergize with cytotoxic therapy, in order to overcome resistance that
      can develop with current therapeutics. A chemistry-driven drug discovery screen
      was employed to identify novel compounds that inhibit endothelial cell tubule
      formation. Cell-based phenotypic screening revealed that noncytotoxic
      concentrations of (Z)-(+/-)-2-(1-benzenesulfonylindol-3-ylmethylene)-1
      azabicyclo[2. 2.2]octan-3-ol (analog I) and (Z)-(+/-)-2-(1-benzylindol-3
      ylmethylene)-1-azabicyclo[2.2.2]octan-3-ol (analog II) inhibited endothelial cell
      migration and the ability to form capillary-like structures in Matrigel by > or
      =70%. The ability to undergo neoangiogenesis, as measured in a window-chamber
      model, was also inhibited by 70%. Screening of biochemical pathways revealed that
      analog II inhibited the enzyme ENOX1 (EC(50) = 10 microM). Retroviral-mediated
      shRNA suppression of endothelial ENOX1 expression inhibited cell migration and
      tubule formation, recapitulating the effects observed with the small-molecule
      analogs. Genetic or chemical suppression of ENOX1 significantly increased
      radiation-mediated Caspase3-activated apoptosis, coincident with suppression of
      p70S6K1 phosphorylation. Administration of analog II prior to fractionated X
      irradiation significantly diminished the number and density of tumor
      microvessels, as well as delayed syngeneic and xenograft tumor growth compared to
      results obtained with radiation alone. Analysis of necropsies suggests that the
      analog was well tolerated. These results suggest that targeting ENOX1 activity
      represents a novel therapeutic strategy for enhancing the radiation response of
      tumors.

PMID- 19395478
TI  - Acetylcholine binding protein of mollusks is unlikely to act as a regulator of
      cholinergic neurotransmission at neurite-neurite synaptic sites in vivo.
AB  - A population of glial cells in the central nervous system of the gastropod
      mollusk Lymnaea stagnalis produces a soluble protein that specifically binds
      acetylcholine. This protein is named the acetylcholine binding protein (AChBP).
      Experiments performed in vitro indicated that AChBP inactivates released
      acetylcholine at cholinergic synapses. On the basis of these observations, a
      similar in vivo role for AChBP was hypothesized. To fulfill this function, AChBP
      expressing glia ought to be located in close proximity to cholinergic synapses in
      vivo. To examine this, we have analyzed the cellular and subcellular expression
      of AChBP in the intact CNS. Using a variety of molecular techniques, we
      demonstrate here that AChBP expression is confined to a subpopulation of glial
      cells located within the peripheral zone of each of the ganglia constituting the
      CNS. This zone contains the cell bodies of neurons, but few synapses. Conversely,
      glial cells that do not express the AChBP are predominantly located in the
      synapse-rich central neuropile zone but are rare in the cell body zone. Thus, our
      findings are not compatible with the previous conclusions drawn from in vitro
      studies and suggest that AChBP functions in vivo as a regulator of nonsynaptic
      cholinergic transmission.

PMID- 19395477
TI  - Peroxisome proliferator-activated receptor-gamma abrogates Smad-dependent
      collagen stimulation by targeting the p300 transcriptional coactivator.
AB  - Ligands of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) abrogate
      the stimulation of collagen gene transcription induced by transforming growth
      factor-beta (TGF-beta). Here, we delineate the mechanisms underlying this
      important novel physiological function for PPAR-gamma in connective tissue
      homeostasis. First, we demonstrated that antagonistic regulation of TGF-beta
      activity by PPAR-gamma ligands involves cellular PPAR-gamma, since 15-deoxy
      Delta12,14-prostaglandin J(2) (15d-PGJ(2)) failed to block TGF-beta-induced
      responses in either primary cultures of PPAR-gamma-null murine embryonic
      fibroblasts, or in normal human skin fibroblasts with RNAi-mediated knockdown of
      PPAR-gamma. Next, we examined the molecular basis underlying the abrogation of
      TGF-beta signaling by PPAR-gamma in normal human fibroblasts in culture. The
      results demonstrated that Smad-dependent transcriptional responses were blocked
      by PPAR-gamma without preventing Smad2/3 activation. In contrast, the interaction
      between activated Smad2/3 and the transcriptional coactivator and histone
      acetyltransferase p300 induced by TGF-beta, and the accumulation of p300 on
      consensus Smad-binding DNA sequences and histone H4 hyperacetylation at the
      COL1A2 locus, were all prevented by PPAR-gamma. Wild-type p300, but not a mutant
      form of p300 lacking functional histone acetyltransferase, was able to restore
      TGF-beta-induced stimulation of COL1A2 in the presence of PPAR-gamma ligands.
      Collectively, these results indicate that PPAR-gamma blocked Smad-mediated
      transcriptional responses by preventing p300 recruitment and histone H4
      hyperacetylation, resulting in the inhibition of TGF-beta-induced collagen gene
      expression. Pharmacological activation of PPAR-gamma thus may represent a novel
      therapeutic approach to target p300-dependent TGF-beta profibrotic responses such
      as stimulation of collagen gene expression.

PMID- 19395479
TI  - A novel allele of kaiA shortens the circadian period and strengthens interaction
      of oscillator components in the cyanobacterium Synechococcus elongatus PCC 7942.
AB  - The basic circadian oscillator of the unicellular fresh water cyanobacterium
      Synechococcus elongatus PCC 7942, the model organism for cyanobacterial circadian
      clocks, consists of only three protein components: KaiA, KaiB, and KaiC. These
      proteins, all of which are homomultimers, periodically interact to form large
      protein complexes with stoichiometries that depend on the phosphorylation state
      of KaiC. KaiA stimulates KaiC autophosphorylation through direct physical
      interactions. Screening a library of S. elongatus transposon mutants for
      circadian clock phenotypes uncovered an atypical short-period mutant that carries
      a kaiA insertion. Genetic and biochemical analyses showed that the short-period
      phenotype is caused by the truncation of KaiA by three amino acid residues at its
      C terminus. The disruption of a negative element upstream of the kaiBC promoter
      was another consequence of the insertion of the transposon; when not associated
      with a truncated kaiA allele, this mutation extended the circadian period. The
      circadian rhythm of KaiC phosphorylation was conserved in these mutants, but with
      some modifications in the rhythmic pattern of KaiC phosphorylation, such as the
      ratio of phosphorylated to unphosphorylated KaiC and the relative phase of the
      circadian phosphorylation peak. The results showed that there is no correlation
      between the phasing of the KaiC phosphorylation pattern and the rhythm of gene
      expression, measured as bioluminescence from luciferase reporter genes. The
      interaction between KaiC and the truncated KaiA was stronger than normal, as
      shown by fluorescence anisotropy analysis. Our data suggest that the KaiA-KaiC
      interaction and the circadian pattern of KaiC autophosphorylation are both
      important for determining the period, but not the relative phasing, of circadian
      rhythms in S. elongatus.

PMID- 19395480
TI  - In vivo sensitivity of blue-light-dependent signaling mediated by AppA/PpsR or
      PrrB/PrrA in Rhodobacter sphaeroides.
AB  - Formation of photosynthesis complexes in Rhodobacter sphaeroides is regulated in
      a redox- and light-dependent manner by the AppA/PpsR and PrrB/PrrA systems. While
      on the one hand, blue light is sensed by the flavin adenine dinucleotide-binding
      BLUF domain of AppA, on the other, light is absorbed by bacteriochlorophyll
      signals through PrrB/PrrA. We show that much smaller quantities initiate the AppA
      mediated response to blue light than the bacteriochlorophyll-mediated response.

PMID- 19395481
TI  - The quorum sensing-dependent gene katG of Burkholderia glumae is important for
      protection from visible light.
AB  - Quorum sensing (QS) plays important roles in the pathogenicity of Burkholderia
      glumae, the causative agent of bacterial rice grain rot. We determined how QS is
      involved in catalase expression in B. glumae. The QS-defective mutant of B.
      glumae exhibited less catalase activity than wild-type B. glumae. A beta
      glucuronidase assay of a katG::Tn3-gusA78 reporter fusion protein revealed that
      katG expression is under the control of QS. Furthermore, katG expression was
      upregulated by QsmR, a transcriptional activator for flagellar-gene expression
      that is regulated by QS. A gel mobility shift assay confirmed that QsmR directly
      activates katG expression. The katG mutant produced toxoflavin but exhibited less
      severe disease than BGR1 on rice panicles. Under visible light conditions and a
      photon flux density of 61.6 micromol(-1) m(-2), the survival rate of the katG
      mutant was 10(5)-fold lower than that of BGR1. This suggests that KatG is a major
      catalase that protects bacterial cells from visible light, which probably results
      in less severe disease caused by the katG mutant.

PMID- 19395482
TI  - An IcmF family protein, ImpLM, is an integral inner membrane protein interacting
      with ImpKL, and its walker a motif is required for type VI secretion system
      mediated Hcp secretion in Agrobacterium tumefaciens.
AB  - An intracellular multiplication F (IcmF) family protein is a conserved component
      of a newly identified type VI secretion system (T6SS) encoded in many animal and
      plant-associated Proteobacteria. We have previously identified ImpL(M), an IcmF
      family protein that is required for the secretion of the T6SS substrate hemolysin
      coregulated protein (Hcp) from the plant-pathogenic bacterium Agrobacterium
      tumefaciens. In this study, we characterized the topology of ImpL(M) and the
      importance of its nucleotide-binding Walker A motif involved in Hcp secretion
      from A. tumefaciens. A combination of beta-lactamase-green fluorescent protein
      fusion and biochemical fractionation analyses revealed that ImpL(M) is an
      integral polytopic inner membrane protein comprising three transmembrane domains
      bordered by an N-terminal domain facing the cytoplasm and a C-terminal domain
      exposed to the periplasm. impL(M) mutants with substitutions or deletions in the
      Walker A motif failed to complement the impL(M) deletion mutant for Hcp
      secretion, which provided evidence that ImpL(M) may bind and/or hydrolyze
      nucleoside triphosphates to mediate T6SS machine assembly and/or substrate
      secretion. Protein-protein interaction and protein stability analyses indicated
      that there is a physical interaction between ImpL(M) and another essential T6SS
      component, ImpK(L). Topology and biochemical fractionation analyses suggested
      that ImpK(L) is an integral bitopic inner membrane protein with an N-terminal
      domain facing the cytoplasm and a C-terminal OmpA-like domain exposed to the
      periplasm. Further comprehensive yeast two-hybrid assays dissecting ImpL(M)
      ImpK(L) interaction domains suggested that ImpL(M) interacts with ImpK(L) via the
      N-terminal cytoplasmic domains of the proteins. In conclusion, ImpL(M) interacts
      with ImpK(L), and its Walker A motif is required for its function in mediation of
      Hcp secretion from A. tumefaciens.

PMID- 19395483
TI  - Characterization of the Escherichia coli ClpY (HslU) substrate recognition site
      in the ClpYQ (HslUV) protease using the yeast two-hybrid system.
AB  - In Escherichia coli, ClpYQ (HslUV) is a two-component ATP-dependent protease in
      which ClpQ is the peptidase subunit and ClpY is the ATPase and the substrate
      binding subunit. The ATP-dependent proteolysis is mediated by substrate
      recognition in the ClpYQ complex. ClpY has three domains, N, I, and C, and these
      domains are discrete and exhibit different binding preferences. In vivo, ClpYQ
      targets SulA, RcsA, RpoH, and TraJ molecules. In this study, ClpY was analyzed to
      identify the molecular determinants required for the binding of its natural
      protein substrates. Using yeast two-hybrid analysis, we showed that domain I of
      ClpY contains the residues responsible for recognition of its natural substrates,
      while domain C is necessary to engage ClpQ. Moreover, the specific residues that
      lie in the amino acid (aa) 137 to 150 (loop 1) and aa 175 to 209 (loop 2) double
      loops in domain I of ClpY were shown to be necessary for natural substrate
      interaction. Additionally, the two-hybrid system, together with random PCR
      mutagenesis, allowed the isolation of ClpY mutants that displayed a range of
      binding activities with SulA, including a mutant with no SulA binding trait.
      Subsequently, via methyl methanesulfonate tests and cpsB::lacZ assays with, e.g.,
      SulA and RcsA as targets, we concluded that aa 175 to 209 of loop 2 are involved
      in the tethering of natural substrates, and it is likely that both loops, aa 137
      to 150 and aa 175 to 209, of ClpY domain I may assist in the delivery of
      substrates into the inner core for ultimate degradation by ClpQ.

PMID- 19395484
TI  - Decarboxylating and nondecarboxylating glutaryl-coenzyme A dehydrogenases in the
      aromatic metabolism of obligately anaerobic bacteria.
AB  - In anaerobic bacteria using aromatic growth substrates, glutaryl-coenzyme A (CoA)
      dehydrogenases (GDHs) are involved in the catabolism of the central intermediate
      benzoyl-CoA to three acetyl-CoAs and CO(2). In this work, we studied GDHs from
      the strictly anaerobic, aromatic compound-degrading organisms Geobacter
      metallireducens (GDH(Geo)) (Fe[III] reducing) and Desulfococcus multivorans
      (GDH(Des)) (sulfate reducing). GDH(Geo) was purified from cells grown on benzoate
      and after the heterologous expression of the benzoate-induced bamM gene. The gene
      coding for GDH(Des) was identified after screening of a cosmid gene library.
      Reverse transcription-PCR revealed that its expression was induced by benzoate;
      the product was heterologously expressed and isolated. Both wild-type and
      recombinant GDH(Geo) catalyzed the oxidative decarboxylation of glutaryl-CoA to
      crotonyl-CoA at similar rates. In contrast, recombinant GDH(Des) catalyzed only
      the dehydrogenation to glutaconyl-CoA. The latter compound was decarboxylated
      subsequently to crotonyl-CoA by the addition of membrane extracts from cells
      grown on benzoate in the presence of 20 mM NaCl. All GDH enzymes were purified as
      homotetramers of a 43- to 44-kDa subunit and contained 0.6 to 0.7 flavin adenine
      dinucleotides (FADs)/monomer. The kinetic properties for glutaryl-CoA conversion
      were as follows: for GDH(Geo), the K(m) was 30 +/- 2 microM and the V(max) was
      3.2 +/- 0.2 micromol min(-1) mg(-1), and for GDH(Des), the K(m) was 52 +/- 5
      microM and the V(max) was 11 +/- 1 micromol min(-1) mg(-1). GDH(Des) but not
      GDH(Geo) was inhibited by glutaconyl-CoA. Highly conserved amino acid residues
      that were proposed to be specifically involved in the decarboxylation of the
      intermediate glutaconyl-CoA were identified in GDH(Geo) but are missing in
      GDH(Des). The differential use of energy-yielding/energy-demanding enzymatic
      processes in anaerobic bacteria that degrade aromatic compounds is discussed in
      view of phylogenetic relationships and constraints of overall energy metabolism.

PMID- 19395485
TI  - 6-pyruvoyltetrahydropterin synthase paralogs replace the folate synthesis enzyme
      dihydroneopterin aldolase in diverse bacteria.
AB  - Dihydroneopterin aldolase (FolB) catalyzes conversion of dihydroneopterin to 6
      hydroxymethyldihydropterin (HMDHP) in the classical folate biosynthesis pathway.
      However, folB genes are missing from the genomes of certain bacteria from the
      phyla Chloroflexi, Acidobacteria, Firmicutes, Planctomycetes, and Spirochaetes.
      Almost all of these folB-deficient genomes contain an unusual paralog of the
      tetrahydrobiopterin synthesis enzyme 6-pyruvoyltetrahydropterin synthase (PTPS)
      in which a glutamate residue replaces or accompanies the catalytic cysteine. A
      similar PTPS paralog from the malaria parasite Plasmodium falciparum is known to
      form HMDHP from dihydroneopterin triphosphate in vitro and has been proposed to
      provide a bypass to the FolB step in vivo. Bacterial genes encoding PTPS-like
      proteins with active-site glutamate, cysteine, or both residues were accordingly
      tested together with the P. falciparum gene for complementation of the
      Escherichia coli folB mutation. The P. falciparum sequence and bacterial
      sequences with glutamate or glutamate plus cysteine were active; those with
      cysteine alone were not. These results demonstrate that PTPS paralogs with an
      active-site glutamate (designated PTPS-III proteins) can functionally replace
      FolB in vivo. Recombinant bacterial PTPS-III proteins, like the P. falciparum
      enzyme, mediated conversion of dihydroneopterin triphosphate to HMDHP, but other
      PTPS proteins did not. Neither PTPS-III nor other PTPS proteins exhibited
      significant dihydroneopterin aldolase activity. Phylogenetic analysis indicated
      that PTPS-III proteins may have arisen independently in various PTPS lineages.
      Consistent with this possibility, merely introducing a glutamate residue into the
      active site of a PTPS protein conferred incipient activity in the growth
      complementation assay, and replacing glutamate with alanine in a PTPS-III protein
      abolished complementation.

PMID- 19395486
TI  - Identification of genes involved in biofilm formation and respiration via mini
      Himar transposon mutagenesis of Geobacter sulfurreducens.
AB  - Electron transfer from cells to metals and electrodes by the Fe(III)-reducing
      anaerobe Geobacter sulfurreducens requires proper expression of redox proteins
      and attachment mechanisms to interface bacteria with surfaces and neighboring
      cells. We hypothesized that transposon mutagenesis would complement targeted
      knockout studies in Geobacter spp. and identify novel genes involved in this
      process. Escherichia coli mating strains and plasmids were used to develop a
      conjugation protocol and deliver mini-Himar transposons, creating a library of
      over 8,000 mutants that was anaerobically arrayed and screened for a range of
      phenotypes, including auxotrophy for amino acids, inability to reduce Fe(III)
      citrate, and attachment to surfaces. Following protocol validation, mutants with
      strong phenotypes were further characterized in a three-electrode system to
      simultaneously quantify attachment, biofilm development, and respiratory
      parameters, revealing mutants defective in Fe(III) reduction but unaffected in
      electron transfer to electrodes (such as an insertion in GSU1330, a putative
      metal export protein) or defective in electrode reduction but demonstrating wild
      type biofilm formation (due to an insertion upstream of the NHL domain protein
      GSU2505). An insertion in a putative ATP-dependent transporter (GSU1501)
      eliminated electrode colonization but not Fe(III) citrate reduction. A more
      complex phenotype was demonstrated by a mutant containing an insertion in a
      transglutaminase domain protein (GSU3361), which suddenly ceased to respire when
      biofilms reached approximately 50% of the wild-type levels. As most insertions
      were not in cytochromes but rather in transporters, two-component signaling
      proteins, and proteins of unknown function, this collection illustrates how
      biofilm formation and electron transfer are separate but complementary
      phenotypes, controlled by multiple loci not commonly studied in Geobacter spp.

PMID- 19395487
TI  - Contribution of lipoproteins and lipoprotein processing to endocarditis virulence
      in Streptococcus sanguinis.
AB  - Streptococcus sanguinis is an important cause of infective endocarditis. Previous
      studies have identified lipoproteins as virulence determinants in other
      streptococcal species. Using a bioinformatic approach, we identified 52 putative
      lipoprotein genes in S. sanguinis strain SK36 as well as genes encoding the
      lipoprotein-processing enzymes prolipoprotein diacylglyceryl transferase (lgt)
      and signal peptidase II (lspA). We employed a directed signature-tagged
      mutagenesis approach to systematically disrupt these genes and screen each mutant
      for the loss of virulence in an animal model of endocarditis. All mutants were
      viable. In competitive index assays, mutation of a putative phosphate transporter
      reduced in vivo competitiveness by 14-fold but also reduced in vitro viability by
      more than 20-fold. Mutations in lgt, lspA, or an uncharacterized lipoprotein gene
      reduced competitiveness by two- to threefold in the animal model and in broth
      culture. Mutation of ssaB, encoding a putative metal transporter, produced a
      similar effect in culture but reduced in vivo competiveness by >1,000-fold.
      [(3)H]palmitate labeling and Western blot analysis confirmed that the lgt mutant
      failed to acylate lipoproteins, that the lspA mutant had a general defect in
      lipoprotein cleavage, and that SsaB was processed differently in both mutants.
      These results indicate that the loss of a single lipoprotein, SsaB, dramatically
      reduces endocarditis virulence, whereas the loss of most other lipoproteins or of
      normal lipoprotein processing has no more than a minor effect on virulence.

PMID- 19395488
TI  - Role of quorum sensing in Sinorhizobium meliloti-Alfalfa symbiosis.
AB  - The ExpR/Sin quorum-sensing system of the gram-negative soil bacterium
      Sinorhizobium meliloti plays an important role in the establishment of symbiosis
      with its host plant Medicago sativa. A mutant unable to produce autoinducer
      signal molecules (sinI) is deficient in its ability to invade the host, but
      paradoxically, a strain lacking the quorum-sensing transcriptional regulator ExpR
      is as efficient as the wild type. We compared the whole-genome expression profile
      of the wild-type strain with strains missing one of the quorum-sensing regulatory
      components to identify genes controlled by the ExpR/Sin system throughout the
      different phases of the bacterial growth cycle, as well as in planta. Our
      analyses revealed that ExpR is a highly versatile regulator with a unique ability
      to show different regulatory capabilities in the presence or absence of an
      autoinducer. In addition, this study provided us with insight into the plant
      invasion defect displayed by the autoinducer mutant. We also discovered that the
      ExpR/Sin quorum-sensing system is repressed after plant invasion. Therefore,
      quorum sensing plays a crucial role in the regulation of many cell functions that
      ensures the successful invasion of the host and is inactivated once symbiosis is
      established.

PMID- 19395489
TI  - ResDE-dependent regulation of enterotoxin gene expression in Bacillus cereus:
      evidence for multiple modes of binding for ResD and interaction with Fnr.
AB  - In the food-borne pathogen Bacillus cereus F4430/73, the production of major
      virulence factors hemolysin BL (Hbl) and nonhemolytic enterotoxin (Nhe) is
      regulated through complex mechanisms. The two-component regulatory system ResDE
      is involved in the activation of hbl and nhe transcription. Here, the response
      regulator ResD and the sensor kinase ResE were overexpressed and purified, and
      autophosphorylation of ResE and transphosphorylation of ResD by ResE were
      demonstrated in vitro. ResD is mainly monomeric in solution, regardless of its
      phosphorylation state. ResD was shown to interact directly with promoter regions
      (p) of the enterotoxin regulator genes resDE, fnr, and plcR and the enterotoxin
      structural genes nhe and hbl, but with different affinities. Binding of ResD to
      pplcR, pnhe, and phbl was not dependent on the ResD phosphorylation status. In
      contrast, ResD phosphorylation significantly increased interactions between ResD
      and presDE and pfnr. Taken together, these results showed that phosphorylation of
      ResD results in a different target expression pattern. Furthermore, ResD and the
      redox activator Fnr were found to physically interact and simultaneously bind
      their target DNAs. We propose that unphosphorylated ResD acts as an antiactivator
      of Fnr, while phosphorylated ResD acts as a coactivator of Fnr. Finally, our
      findings represent the first molecular evidence of the role of ResDE as a
      sentinel system capable of sensing redox changes and coordinating a response that
      modulates B. cereus virulence.

PMID- 19395490
TI  - Subcellular localization of TatAd of Bacillus subtilis depends on the presence of
      TatCd or TatCy.
AB  - The gram-positive bacterium Bacillus subtilis contains two minimal Tat
      translocases, TatAdCd and TatAyCy, which are each involved in the secretion of
      one or more specific protein substrates. We have investigated the subcellular
      localization of the TatA components by employing C-terminal green fluorescent
      protein (GFP) fusions and fluorescence microscopy. When expressed from a xylose
      inducible promoter, the TatA-GFP fusion proteins displayed a dual localization
      pattern, being localized peripherally and showing bright foci which are
      predominantly located at the division sites and/or poles of the cells.
      Importantly, the localization of TatAd-GFP was similar when the protein was
      expressed from its own promoter under phosphate starvation conditions, indicating
      that these foci are not the result of artificial overexpression. Moreover, the
      TatAd-GFP fusion protein was shown to be functional in the translocation of its
      substrate PhoD, provided that TatCd is also present. Furthermore, we demonstrate
      that the localization of TatAd-GFP in foci depends on the presence of the TatCd
      component. Remarkably, however, the TatAd-GFP foci can also be observed in the
      presence of TatCy, indicating that TatAd can interact not only with TatCd but
      also with TatCy. These results suggest that the formation of TatAd complexes in
      B. subtilis is controlled by TatC.

PMID- 19395491
TI  - Characterization of a serine/threonine kinase involved in virulence of
      Staphylococcus aureus.
AB  - Staphylococcus aureus is a common human cutaneous and nasal commensal and a major
      life-threatening pathogen. Adaptation to the different environments encountered
      inside and outside the host is a crucial requirement for survival and
      colonization. We identified and characterized a eukaryotic-like serine/threonine
      kinase with three predicted extracellular PASTA domains (SA1063, or Stk1) and its
      associated phosphatase (SA1062, or Stp1) in S. aureus. Biochemical analyses
      revealed that Stk1 displays autokinase activity on threonine and serine residues
      and is localized to the membrane. Stp1 is a cytoplasmic protein with manganese
      dependent phosphatase activity toward phosphorylated Stk1. In-frame deletions of
      the stk1 and stp1 genes were constructed in S. aureus strain 8325-4. Phenotypic
      analyses of the mutants revealed reduced growth of the stk1 mutant in RPMI 1640
      defined medium that was restored when adenine was added to the medium.
      Furthermore, the stk1 mutant displayed increased resistance to Triton X-100 and
      to fosfomycin, suggesting modifications in cell wall metabolism. The stk1 mutant
      was tested for virulence in a mouse pyelonephritis model and found to be strongly
      reduced for survival in the kidneys (approximately 2-log-unit decrease) compared
      to the parental strain. Renal histopathological analyses showed severe
      inflammatory lesions in mice infected with the parental S. aureus SH1000 strain,
      whereas the Deltastk1 mutant led to only minimal renal lesions. These results
      confirm the important role of Stk1 for full expression of S. aureus pathogenesis
      and suggest that phosphorylation levels controlled by stk1 are essential in
      controlling bacterial survival within the host.

PMID- 19395492
TI  - Involvement of a membrane-bound class III adenylate cyclase in regulation of
      anaerobic respiration in Shewanella oneidensis MR-1.
AB  - Unlike other bacteria that use FNR to regulate anaerobic respiration, Shewanella
      oneidensis MR-1 uses the cyclic AMP receptor protein (CRP) for this purpose.
      Three putative genes, cyaA, cyaB, and cyaC, predicted to encode class I, class
      IV, and class III adenylate cyclases, respectively, have been identified in the
      genome sequence of this bacterium. Functional validation through complementation
      of an Escherichia coli cya mutant confirmed that these genes encode proteins with
      adenylate cyclase activities. Chromosomal deletion of either cyaA or cyaB did not
      affect anaerobic respiration with fumarate, dimethyl sulfoxide (DMSO), or
      Fe(III), whereas deletion of cyaC caused deficiencies in respiration with DMSO
      and Fe(III) and, to a lesser extent, with fumarate. A phenotype similar to that
      of a crp mutant, which lacks the ability to grow anaerobically with DMSO,
      fumarate, and Fe(III), was obtained when both cyaA and cyaC were deleted.
      Microarray analysis of gene expression in the crp and cyaC mutants revealed the
      involvement of both genes in the regulation of key respiratory pathways, such as
      DMSO, fumarate, and Fe(III) reduction. Additionally, several genes associated
      with plasmid replication, flagellum biosynthesis, and electron transport were
      differentially expressed in the cyaC mutant but not in the crp mutant. Our
      results indicated that CyaC plays a major role in regulating anaerobic
      respiration and may contribute to additional signaling pathways independent of
      CRP.

PMID- 19395493
TI  - Autoproteolysis of YscU of Yersinia pseudotuberculosis is important for
      regulation of expression and secretion of Yop proteins.
AB  - YscU of Yersinia can be autoproteolysed to generate a 10-kDa C-terminal
      polypeptide designated YscU(CC). Autoproteolysis occurs at the conserved N
      downward arrowPTH motif of YscU. The specific in-cis-generated point mutants
      N263A and P264A were found to be defective in proteolysis. Both mutants expressed
      and secreted Yop proteins (Yops) in calcium-containing medium (+Ca(2+)
      conditions) and calcium-depleted medium (-Ca(2+) conditions). The level of Yop
      and LcrV secretion by the N263A mutant was about 20% that of the wild-type
      strain, but there was no significant difference in the ratio of the different
      secreted Yops, including LcrV. The N263A mutant secreted LcrQ regardless of the
      calcium concentration in the medium, corroborating the observation that Yops were
      expressed and secreted in Ca(2+)-containing medium by the mutant. YscF, the type
      III secretion system (T3SS) needle protein, was secreted at elevated levels by
      the mutant compared to the wild type when bacteria were grown under +Ca(2+)
      conditions. YscF secretion was induced in the mutant, as well as in the wild
      type, when the bacteria were incubated under -Ca(2+) conditions, although the
      mutant secreted smaller amounts of YscF. The N263A mutant was cytotoxic for HeLa
      cells, demonstrating that the T3SS-mediated delivery of effectors was functional.
      We suggest that YscU blocks Yop release and that autoproteolysis is required to
      relieve this block.

PMID- 19395494
TI  - Molecular dissection of the secA2 locus of group B Streptococcus reveals that
      glycosylation of the Srr1 LPXTG protein is required for full virulence.
AB  - In streptococci, the secA2 locus includes genes encoding the following: (i) the
      accessory Sec components (SecA2, SecY2, and at least three accessory secretion
      proteins), (ii) two essential glycosyltranferases (GTs) (GtfA and GtfB), (iii) a
      variable number of dispensable additional GTs, and (iv) a secreted serine-rich
      LPXTG protein which is glycosylated in the cytoplasm and transported to the cell
      surface by this accessory Sec system. The secA2 locus of Streptococcus agalactiae
      strain NEM316 is structurally related to those found in other streptococci and
      encodes the serine-rich surface protein Srr1. We demonstrated that expression of
      Srr1 but not that of the SecA2 components and the associated GTs is regulated by
      the standalone transcriptional regulator Rga. Srr1 is synthesized as a
      glycosylated precursor, secreted by the SecA2 system, and anchored to the cell
      wall by the housekeeping sortase A. Srr1 was localized preferentially at the old
      poles. GtfA and/or GtfB, but not the six additional GTs, is essential for the
      production of Srr1. These GTs are involved in the attachment of GlcNac and sialic
      acid to Srr1. Full glycosylation of Srr1 is associated with the cell surface
      display of a protein that is more resistant to proteolytic attack. Srr1
      contributes to bacterial adherence to human epithelial cell lines and virulence
      in a neonatal rat model. The extent of Srr1 glycosylation by GtfC to -H modulates
      bacterial adherence and virulence.

PMID- 19395495
TI  - OscR, a new osmolarity-responsive regulator in Vibrio cholerae.

PMID- 19395496
TI  - Characterization of the Corynebacterium glutamicum deltapimB' deltamgtA double
      deletion mutant and the role of Mycobacterium tuberculosis orthologues Rv2188c
      and Rv0557 in glycolipid biosynthesis.
AB  - In this study, utilizing a Corynebacterium glutamicum DeltapimB' DeltamgtA double
      deletion mutant, we unequivocally assign the in vivo functions of Rv2188c as an
      Ac(1)PIM(1):mannosyltransferase (originally termed PimB'(Mt) [Mycobacterium
      tuberculosis PimB']) and Rv0557 as a GlcAGroAc(2):mannosyltransferase (originally
      termed PimB(Mt)), which we have reassigned as PimB(Mt) and MgtA(Mt),
      respectively, in Mycobacterium tuberculosis.

PMID- 19395497
TI  - Active transcription of rRNA operons condenses the nucleoid in Escherichia coli:
      examining the effect of transcription on nucleoid structure in the absence of
      transertion.
AB  - In Escherichia coli the genome must be compacted approximately 1,000-fold to be
      contained in a cellular structure termed the nucleoid. It is proposed that the
      structure of the nucleoid is determined by a balance of multiple compaction
      forces and one major expansion force. The latter is mediated by transertion, a
      coupling of transcription, translation, and translocation of nascent membrane
      proteins and/or exported proteins. In supporting this notion, it has been shown
      consistently that inhibition of transertion by the translation inhibitor
      chloramphenicol results in nucleoid condensation due to the compaction forces
      that remain active in the cell. Our previous study showed that during optimal
      growth, RNA polymerase is concentrated into transcription foci or "factories,"
      analogous to the eukaryotic nucleolus, indicating that transcription and RNA
      polymerase distribution affect the nucleoid structure. However, the
      interpretation of the role of transcription in the structure of the nucleoid is
      complicated by the fact that transcription is implicated in both compacting
      forces and the expansion force. In this work, we used a new approach to further
      examine the effect of transcription, specifically from rRNA operons, on the
      structure of the nucleoid, when the major expansion force was eliminated. Our
      results showed that transcription is necessary for the chloramphenicol-induced
      nucleoid compaction. Further, an active transcription from multiple rRNA operons
      in chromosome is critical for the compaction of nucleoid induced by inhibition of
      translation. All together, our data demonstrated that transcription of rRNA
      operons is a key mechanism affecting genome compaction and nucleoid structure.

PMID- 19395498
TI  - Dysglycaemia, cardiovascular outcome and treatment. Is the jury still out?

PMID- 19395499
TI  - Comparison of the use of liquid crystal thermometers with glass mercury
      thermometers in febrile children in a children's ward at Port Moresby General
      Hospital, Papua New Guinea.
AB  - We compared the temperatures recorded, in febrile children admitted to a
      children's ward at Port Moresby General Hospital, by a doctor and by a group of
      nurses using glass mercury thermometers (GMT) and liquid crystal thermometers
      (LCT, Nextemp and Traxit. The mean difference (with 95% confidence intervals) in
      temperatures between GMT and Nextemp were -0.12 degrees C (-0.16 degrees C to 
      0.08 degrees C) for the doctor and 0.12 degrees C (0.04-0.20 degrees C) for
      nurses. The mean difference in temperatures between GMT and Traxit were -0.05
      degrees C (-0.09 degrees C to -0.01 degrees C) for the doctor and 0.19 degrees C
      (0.10-0.28 degrees C) for the nurses. A similar result was obtained when one of
      the Nextemp thermometers used in the initial study was compared with GMT on a
      small sample of patients by the doctor 8 months later. Limited evaluation showed
      nursing staff were in favour of using the LCTs. Nextemp and Traxit thermometers
      can be used interchangeably with GMT in this setting.

PMID- 19395500
TI  - Haemorrhagic cardiac tamponade: a rare complication of pneumonia.

PMID- 19395503
TI  - S-nitrosoglutathione reductase: an important regulator in human asthma.
AB  - RATIONALE: Nitric oxide bioactivity, mediated through the formation of S
      nitrosothiols (SNOs), has a significant effect on bronchomotor tone. S
      Nitrosoglutathione is an endogenous bronchodilator that is decreased in children
      with asthmatic respiratory failure and in adults with asthma undergoing segmental
      airway challenge. Recently we showed that S-nitrosoglutathione reductase (GSNOR)
      regulates endogenous SNOs. Mice with genetic deletion of GSNOR are protected from
      airway hyperresponsivity in an allergic asthma model. OBJECTIVES: We hypothesized
      that GSNOR is increased in human asthma and correlates with lung SNO content and
      airway reactivity. METHODS: We recruited 36 subjects with mild asthma with FEV(1)
      88.5 +/- 2.3% predicted and 34 healthy control subjects with FEV(1) 100.7 +/-
      2.5% predicted. Bronchoalveolar lavage (BAL) was performed in all subjects. Cell
      counts, differentials, GSNOR activity, and SNO levels were determined in BAL.
      MEASUREMENTS AND MAIN RESULTS: SNO content was decreased in asthmatic BAL
      compared with control BAL and correlated inversely with GSNOR expression in BAL
      cell lysates. Furthermore, GSNOR activity measured from BAL samples was
      significantly increased in subjects with asthma compared with control subjects
      and correlated inversely with the provocative concentration of methacholine
      causing a 20% decrease in FEV(1). CONCLUSIONS: These findings suggest that GSNOR
      is an important regulator of airway SNO content and airways hyperresponsiveness
      in human asthma.

PMID- 19395504
TI  - Pro: The evidence for a causal role of dust mites in asthma.

PMID- 19395505
TI  - Con: House dust mites in atopic diseases: accused for 45 years but not guilty?

PMID- 19395506
TI  - Polymorphisms in positional candidate genes on BTA14 and BTA26 affect carcass
      quality in beef cattle.
AB  - Several studies have reported the presence of carcass quality QTL on BTA14 and
      BTA26, with no specific genes being conclusively linked as their cause. The aim
      of this study was to identify polymorphisms in genes known to affect lipid
      metabolism in other species and to assess their association with carcass quality
      traits. Two genes located on BTA14, 2,4 dienoyl CoA reductase 1 (DECR1) and core
      binding factor, runt domain, alpha subunit 2, translocated to 1 gene (CBFA2T1),
      have been previously evaluated in other species and found to contain
      polymorphisms influencing lipid metabolism. A gene on BTA26, fibroblast growth
      factor 8 (FGF8), has in recent studies been linked to several QTL affecting
      obesity in mice, indicating its potential for regulating adiposity in other
      species. Sequencing analysis identified 9 polymorphisms in DECR1, 4 in CBFA2T1,
      and 4 in FGF8. Multiple sequence alignment of DECR1 among cattle, humans, and
      mice showed that 4 of these mutations lie in conserved regions across these
      species. Using 464 Angus, Charolais, and crossbred animals produced associations
      with ultrasound marbling score (CBFA2T1, P = 0.019), ultrasound backfat (DECR1, P
      = 0.012), carcass backfat (FGF8, P = 0.004), and lean meat yield (FGF8, P =
      0.005). Quantitative trait loci analysis including a set of previously genotyped
      markers on BTA14, and 1 DECR1 polymorphism resulted in several significant QTL
      peaks: ultrasound backfat (UBF) at 91 cM, lean meat yield at 86 cM, carcass
      gradefat at 15 cM, and yield grade at 87 cM, all at the P < 0.05 level. Using
      DECR1 as a genetic covariate removed the UBF QTL, indicating that this SNP was
      contributing to the variation observed in UBF. A similar analysis was performed
      on BTA26 using 1 of the FGF8 polymorphisms. Results showed significant peaks for
      lean meat yield at 2 cM and for yield grade at 25 cM, both at P < 0.01, and for
      carcass backfat at 25 cM (P < 0.05). Removal of FGF8 SNP in further analysis
      resulted in the disappearance of the carcass backfat QTL. These results suggest
      that polymorphisms discovered in DECR1, CBFA2T1, and FGF8 may play a role in the
      lipid metabolism pathway affecting carcass quality traits in beef cattle.
      However, further studies are needed to confirm that these polymorphisms are
      responsible for the differences observed in carcass quality in beef cattle.

PMID- 19395507
TI  - Product versus additive threshold models for analysis of reproduction outcomes in
      animal genetics.
AB  - The phenotypic observation of some reproduction traits (e.g., insemination
      success, interval from lambing to insemination) is the result of environmental
      and genetic factors acting on 2 individuals: the male and female involved in a
      mating couple. In animal genetics, the main approach (called additive model)
      proposed for studying such traits assumes that the phenotype is linked to a
      purely additive combination, either on the observed scale for continuous traits
      or on some underlying scale for discrete traits, of environmental and genetic
      effects affecting the 2 individuals. Statistical models proposed for studying
      human fecundability generally consider reproduction outcomes as the product of
      hypothetical unobservable variables. Taking inspiration from these works, we
      propose a model (product threshold model) for studying a binary reproduction
      trait that supposes that the observed phenotype is the product of 2 unobserved
      phenotypes, 1 for each individual. We developed a Gibbs sampling algorithm for
      fitting a Bayesian product threshold model including additive genetic effects and
      showed by simulation that it is feasible and that it provides good estimates of
      the parameters. We showed that fitting an additive threshold model to data that
      are simulated under a product threshold model provides biased estimates,
      especially for individuals with high breeding values. A main advantage of the
      product threshold model is that, in contrast to the additive model, it provides
      distinct estimates of fixed effects affecting each of the 2 unobserved
      phenotypes.

PMID- 19395508
TI  - Invited review: research contributions from seventy-five years of breeding Line 1
      Hereford cattle at Miles City, Montana.
AB  - For 75 yr, Line 1 Hereford cattle have been at the forefront of beef cattle
      breeding research. The goal of this review is to provide an overview of
      scientific contributions made using the Line 1 Hereford population. It was
      initially developed as contribution to a western regional program from which beef
      producers were envisioned to use heterosis by crossing selected inbred lines.
      Whereas this vision was never fulfilled, being largely supplanted by
      crossbreeding, Line 1 has had a profound influence on beef cattle breeding
      research and the Hereford breed. For more than 60 yr, Hereford breeders and
      commercial beef producers have purchased Line 1 Hereford germplasm for use in
      their herds. By example, Line 1 illustrates a successful line-breeding program
      through which a 39% additive relationship to the founding sire has been
      maintained over more than 18 generations. Procedures for performance testing beef
      cattle can be traced to original research with Line 1. Data from Line 1
      contributed to the first estimates of heritability and genetic correlation for
      beef cattle. Work with Line 1 has also contributed greatly to the understanding
      of maternal genetic effects in beef cattle. Diallel crossing with other inbred
      lines provided early estimates of heterosis for beef cattle, complimented by the
      later observation that heterosis resulted in complete recovery of the accumulated
      negative effects of inbreeding. After exchanges of germplasm with the Northern
      Montana Agricultural Experiment Station at Havre and the Brooksville Beef Cattle
      Research Station in Florida, pioneering comprehensive evaluations of genotype x
      environment interaction were conducted. Breeding practices implemented by USDA
      Agricultural Research Service at Miles City make Line 1 the longest running
      selection experiment using beef cattle worldwide. This long-term database has
      provided an exceptional resource for prototype evaluations of procedures for
      national cattle evaluation, and the results make up an integral part of the
      foundation of modern-day genetic evaluation programs. Having used DNA from Line 1
      in the development of a bacterial artificial chromosome library and the bovine
      genome sequence, Line 1 Hereford cattle are uniquely positioned for continued
      contributions in future research.

PMID- 19395509
TI  - Amino acid digestibility of distillers dried grains with solubles, produced from
      sorghum, a sorghum-corn blend, and corn fed to growing pigs.
AB  - The objective of this experiment was to measure the concentration and
      digestibility of CP and AA in distillers dried grains with solubles (DDGS)
      produced from sorghum (S-DDGS) or a blend of sorghum and corn grains (SC-DDGS),
      and to compare these values with the digestibility of CP and AA in corn-based
      DDGS (C-DDGS). Eleven growing barrows (initial BW = 44.6 +/- 6.5 kg) were
      surgically fitted with a T-cannula in the distal ileum and allotted to a Youden
      square design with 11 diets and 8 periods. One diet contained 66.7% S-DDGS, 1
      diet contained 66.7% SC-DDGS, 8 diets contained 66.7% C-DDGS, and 1 diet was N
      free. Chromic oxide (0.3%) was used in all diets as an indigestible marker. The
      direct procedure was used to measure apparent ileal digestibility (AID) and
      standardized ileal digestibility (SID) of CP and AA in the 10 sources of DDGS.
      Results of the experiment showed that the AID of Lys was not different among S
      DDGS, SC-DDGS, and C-DDGS. The mean SID of CP, Arg, and Lys in C-DDGS were not
      different from values obtained in S-DDGS and SC-DDGS. The SID of Trp in S-DDGS
      (72.0%) was greater (P < 0.01) than in C-DDGS (64.9%), but there was no
      difference between C-DDGS and SC-DDGS (62.4%). The SID of CP and all AA were
      different among the 8 sources of C-DDGS (P < 0.01). Among the indispensable AA,
      Lys had the greatest variation and the SID ranged from 55.7 to 68.7%. The
      concentration of total and digestible AA was highly correlated (r(2)) for Arg
      (0.88), Ile (0.85), Leu (0.82), Phe (0.84), and Trp (0.84), but reduced r(2)
      values were observed for Lys (0.66) and Thr (0.39). A low correlation between the
      concentration and digestibility of AA indicates that it is desirable to develop
      in vitro procedures to predict digestible AA concentration in DDGS. In
      conclusion, SID values for CP and Lys in S-DDGS and SC-DDGS are within the range
      of values obtained in C-DDGS, but for many other AA, SID values in S-DDGS and in
      SC-DDGS are less than in C-DDGS.

PMID- 19395510
TI  - Estimation of the metabolizable energy content of meat and bone meal for swine.
AB  - Experiments were conducted to determine apparent ME (AME) and apparent nitrogen
      corrected ME (AME(n)) of 21 meat and bone meal (MBM) samples and to develop
      regression equations for predicting energy value of MBM. One hundred ninety-eight
      32-kg of BW barrows were used for the study. The 22 treatments consisted of 1
      corn-soybean meal reference diet and 21 test diets in which 21 MBM samples
      replaced 100 g/kg of corn and soybean meal such that the ratio of corn and
      soybean meal was the same in the reference and test diets. The DE, AME, and
      AME(n) of the MBM samples were determined by the difference method in a
      metabolism study consisting of 5-d adjustment and 5 d of total collection of
      feces and urine. On a DM basis, GE of MBM ranged from 3,895 to 5,193 kcal/kg, CP
      ranged from 491 to 641 g/kg, and ash ranged from 142 to 338 g/kg. The AME of the
      MBM samples ranged from 2,320 to 3,872 kcal/kg, whereas AME(n) ranged from 2,212
      to 3,767 kcal/kg. None of the proximate compositions explained >50% of the
      variation in energy content of the MBM. Fat was positively correlated with GE,
      DE, AME, and AME(n) (r < or = 0.44), but CP, ash, Ca, and P were negatively
      correlated with DE, AME, and AME(n). The ratios of the proximate compositions to
      each other were correlated with the energy contents of the MBM. Crude protein:fat
      and GE:fat were negatively correlated with DE, AME, and AME(n) of the MBM (r
      ranged from -0.17 to -0.39), but fat:ash had the greatest positive correlation
      with AME and AME(n) compared with other ratios tested. When the data from 1 MBM
      sample that was an outlier were removed from the analysis, R(2) was 0.42 for AME
      and AME(n). The 4 variables that produced the best prediction equation for AME
      and AME(n) were GE, CP, P, and ash. The prediction equation for AME using these
      variables was AME = 13,587 - (1.25 x GE, kcal/kg) - (3.51 x CP, g/kg) + (30.4 x
      P, g/kg) - (16.4 x Ash, g/kg), and for AME(n), the equation was AME(n) = 13,547 -
      (1.25 x GE, kcal/kg) - (3.59 x CP, g/kg) + (31.0 x P, g/kg) - (16.5 x Ash, g/kg).
      It was concluded from this study that MBM is a good energy source for pigs and
      that, although other extrinsic factors may contribute to the variations in energy
      content of MBM, proximate compositions should be sufficient to predict the energy
      value of MBM for pigs.

PMID- 19395511
TI  - Relationship between feeding behavior and residual feed intake in growing Brangus
      heifers.
AB  - Residual feed intake (RFI) is a measure of feed efficiency defined as the
      difference between actual feed intake and expected feed intake required for
      maintenance and production. The objective of this study was to determine the
      relationship between RFI, feeding behavior, and other performance traits in
      growing heifers. Individual DMI was measured in Brangus heifers (n = 115) fed a
      roughage-based diet (ME = 2.0 Mcal/kg) for 70 d using Calan-gate feeders.
      Residual feed intake was computed as the residuals from linear regression of DMI
      on mid-test BW(0.75) and ADG. Heifers with the greatest (least efficient, n = 18)
      and least (most efficient, n = 18) RFI were identified for quantification of
      feeding behavior traits. Continuous video recordings were obtained for all
      heifers during d 28 through d 56 of the 70-d feeding trial. Video data of 2
      replications of four 24-h periods, 2 wk apart, were analyzed for the focal
      heifers. A head-down feeding event was defined as a heifer positioned in the
      feeder with her head lowered. A meal included all head-down feeding events that
      were separated by less than 300 s. The mean RFI for the high- and low-RFI heifers
      were 1.00 and -1.03 +/- 0.03 kg/d, respectively. High-RFI heifers consumed 21.9%
      more (P < 0.0001) DM but had similar BW and ADG compared with low-RFI heifers.
      The high-RFI heifers spent less time in head-down feeding events per day (P <
      0.0001; 124 vs. 152 +/- 4.3 min/d), consumed DM at a faster rate (99.6 vs. 62.8
      +/- 3.3 g/min), and ate more often per day (119.1 vs. 90.5 +/- 3.9 head-down
      feeding events/d) compared with the low-RFI heifers; however, meal duration and
      frequency were not related to RFI. We conclude that feeding behavior related to
      head-down feeding events may be more useful as an indicator of RFI than the
      number of meal events.

PMID- 19395512
TI  - Video image analysis as a potential grading system for Uruguayan beef carcasses.
AB  - A study was conducted in 2 phases to evaluate the effectiveness of 1) the VIAscan
      Beef Carcass System (BCSys; hot carcass system) and the CVS BeefCam (chilled
      carcass system), used independently or in combination, to predict Uruguayan beef
      carcass fabrication yields; and 2) the CVS BeefCam to segregate Uruguayan beef
      carcasses into groups that differ in the Warner-Bratzler shear force (WBSF)
      values of their LM steaks. The results from the meat yield phase of the present
      study indicated that the prediction of saleable meat yield percentages from
      Uruguayan beef carcasses by use of the BCSys or CVS BeefCam is similar to, or
      slightly better than, the use of USDA yield grade calculated to the nearest 0.1
      and was much more effective than prediction based on Uruguay National Institute
      of Meat (INAC) grades. A further improvement in fabrication yield prediction
      could be obtained by use of a dual-component video image analysis (VIA) system.
      Whichever method of VIA prediction of fabrication yield is used, a single
      predicted value of fabrication yield for every carcass removes an impediment to
      the implementation of a value-based pricing system. Additionally, a VIA method of
      predicting carcass yield has the advantage over the current INAC classification
      system in that estimates would be produced by an instrument rather than by
      packing plant personnel, which would appeal to cattle producers. Results from the
      tenderness phase of the study indicated that the CVS BeefCam output variable for
      marbling was not (P > 0.05) able to segregate steer and heifer carcasses into
      groups that differed in WBSF values. In addition, the results of segregating
      steer and heifer carcasses according to muscle color output variables indicate
      that muscle maturity and skeletal maturity were useful for segregating carcasses
      according to differences in WBSF values of their steaks (P > 0.05). Use of VIA to
      predict beef carcass fabrication yields could improve accuracy and reduce
      subjectivity in comparison with use of current INAC grades. Use of VIA to sort
      carcasses according to muscle color would allow for the marketing of more
      consistent beef products with respect to tenderness. This would help facilitate
      the initiation of a value-based marketing system for the Uruguayan beef industry.

PMID- 19395513
TI  - Immunobiochemical status of sheep exposed to periods of experimental protein
      deficit and realimentation.
AB  - Immunobiochemical status of sheep exposed to periods of experimental protein
      deficit and realimentation was studied in 12 sheep (15 mo) randomly distributed
      into 2 equal groups and fed individually 2 different concentrate supplements
      along with wheat straw to provide 100% (normal protein, NP) or 50% (low protein,
      LP) of CP requirements. The study was comprised of 3 periods; during period 1 (0
      to 13 wk) and 2 (14 to 26 wk) animals in the 2 groups were fed NP and LP diets,
      respectively; during period 3 (27 to 44 wk), animals in the LP group were
      switched over to NP diet to allow realimentation, whereas animals in the NP group
      remained on the same NP diet. Blood was collected from all groups at end of each
      period, and serum glucose, total protein, albumin (sAlb), globulin (sGlb), urea
      (sU), creatinine (sCr), cholesterol, triiodothyronine, and thyroxine
      concentrations were determined. During the same periods, the cell-mediated immune
      (CMI) response was measured by a delayed type hypersensitivity (DTH) assay and in
      vitro nitrite production by lymphocytes. At the end of periods 2 and 3, humoral
      immune response (HIR) was measured by sensitizing the sheep with Brucella abortus
      S99 antigen and measuring antibody titers on 0, 7, 14, 21, and 28 d
      postinoculation by ELISA. Feed intake decreased with prolonged protein deficit
      and showed recovery during period 3. Blood chemistry revealed reduced sAlb
      concentration in the LP group resulting in narrow sAlb:sGlb ratio, increased sCr
      concentrations (P = 0.008) accompanying a decreased (P = 0.004) sU:sCr ratio, and
      decreased glucose concentrations (P = 0.05). Other variables did not change
      significantly between the NP and LP groups. The DTH response at the end of period
      1 and 2 showed marked (P = 0.008) effect of protein restriction on CMI. Nitrite
      production, basal and after lipopolysaccharide stimulation, was greater (P =
      0.04) in the NP group. The HIR was less (P = 0.04) in the LP group during period
      3. Realimentation of protein in the LP group during period 3 showed recovery in
      CMI and HIR. In conclusion, protein deprivation induced a decline in CMI and HIR
      in sheep accompanying alterations in related metabolic profile. However, a marked
      recovery was observed after realimentation.

PMID- 19395514
TI  - Effects of yeast culture supplementation on growth performance, intestinal
      health, and immune response of nursery pigs.
AB  - A total of 216 weaning pigs were used in 2 experiments to determine the effects
      of dietary supplementation of yeast culture (YC) at different dose levels on the
      growth performance, nutrient digestibility, intestinal morphology, intestinal
      microflora, and immune response in weanling pigs and to determine whether YC can
      be a candidate to replace antibiotic growth promoters (AGP). In Exp. 1, 192 pigs
      (7.5 +/- 0.2 kg of BW) weaned at 28 d of age were randomly allotted to 6
      treatments: 1) control (without AGP or YC); 2) AGP (chlortetracycline, 80 mg/kg);
      3) 2.5 g/kg of YC (Diamond V XP Yeast Culture); 4) 5 g/kg of YC; 5) 10 g/kg of
      YC; and 6) 20 g/kg of YC. Each treatment had 8 replicated pens with 4 pigs per
      pen. Pigs were fed the experimental diets for 21 d. Average daily gain of pigs
      fed 5 g/kg of YC was greater (P < 0.05) than that of pigs in the control and
      other YC groups. However, there was no difference between the YC and AGP group.
      Pigs supplemented with 5 g/kg of YC, 10 g/kg of YC, and AGP had a greater (P <
      0.01) ADFI than the control; however, G:F was not affected by treatment. Thus, 5
      g/kg of YC supplementation level was chosen for Exp. 2. In Exp. 2, to elucidate
      the mode of action of YC, 24 nursery pigs (5.8 +/- 0.1 kg of BW; 21 d of age)
      were randomly allotted into 3 treatments for a 21-d trial. Treatments consisted
      of 1) control (without AGP or YC), 2) AGP, and 3) 5 g/kg of YC. Blood samples
      were collected weekly to measure CD4(+), CD8(+) percentage, and blood cytokine
      content. All pigs were harvested to determine treatment effects on gut
      microbiota, morphology, and immune function. Dietary supplementation of 5 g/kg of
      YC improved (P < 0.05) ADG of pigs compared with the control group, but
      performance of pigs fed YC was similar to those fed AGP. Pigs receiving 5 g/kg of
      YC had greater (P < 0.05) digestibility of DM, CP, GE, and jejunal villus height
      and villus height:crypt depth ratio (P < 0.05) compared with pigs fed the control
      diet. However, no differences in performance, digestibility, or gut morphology
      were observed between pigs fed YC and AGP. Gut interferon (IFN)-gamma
      concentrations were greater (P < 0.01) for pigs supplemented with YC compared
      with control pigs and pigs supplemented with AGP on d 21. However, plasma IFN
      gamma concentrations were decreased (P < 0.01) in pigs supplemented with YC and
      AGP compared with control pigs on d 7, and CD4(+) was decreased (P < 0.01) in
      pigs supplemented with YC and AGP on d 14. Results indicate that dietary YC
      supplementation at 5 g/kg had a positive effect on growth performance of nursery
      pigs by improving jejunal villus height and villus height:crypt depth ratio and
      by modulating gut immune response. The comparable effect of 5 g/kg of YC
      supplementation and AGP on the growth performance of nursery pigs indicates that
      YC may be a good candidate as an antibiotic alternative.

PMID- 19395515
TI  - George Washington Litton, 1910 to 1989: a brief biography.

PMID- 19395516
TI  - Variation in digestible energy content of Australian sweet lupins (Lupinus
      angustifolius L.) and the development of prediction equations for its estimation.
AB  - Sixty-three male pigs (Landrace x Large White) weighing 49.5 +/- 0.40 kg were
      used to (1) examine the variation in DE content of Lupinus angustifolius L. in
      relation to variety and geographical growing region and (2) establish prediction
      equations for DE content from physical and chemical composition. The pigs were
      randomly allocated to a 4 x 2 factorial treatment design with respective factors
      being 4 varieties (cv. Belara, Coromup, Mandelup, and Tanjil) and 2 growing
      locations (northern and southern agricultural areas of Western Australia). In
      addition, a wheat control diet was fed as a reference for calculation of lupin DE
      content. The lupins were ground through a hammer mill fitted with a 4-mm screen
      to a mean particle size of 888 mum. Pigs were fed their respective experimental
      diets at 3 times maintenance energy level [3 x (0.458 x BW(0.75))/diet DE] in the
      study. The DE content of lupins ranged from 13.3 to 15.7 MJ/kg with a mean value
      of 14.2 MJ/kg. Variety of lupins affected (P < 0.01) the DE content, and lupins
      grown in the northern agricultural region had a greater DE content than the same
      lupins grown in the southern agricultural area (P < 0.01). Although the variation
      in DE content of lupins was mostly caused by significantly greater DE content of
      cv. Coromup grown in the northern agricultural region, the results suggest that
      genetic and environmental conditions during the growth of lupins have a
      significant impact on the utilization of energy in grower pigs. Simple regression
      analysis showed that prediction of DE content was possible from the proportion of
      hulls [R(2) = 0.88, residual SD (RSD) = 1.116, P < 0.001], 1,000-seed weight
      (R(2) = 0.77, RSD = 1.092, P < 0.01), and soluble arabinoxylan content (R(2) =
      0.64, RSD = 1.072, P < 0.05). Multiple regression analysis showed that adding
      total nonstarch polysaccharide (R(2) = 0.96, RSD = 1.187, P < 0.01) and soluble
      nonstarch polysaccharide (R(2) = 0.95, RSD = 1.200, P < 0.01) to the equation
      along with the proportion of hull and 1,000-seed weight significantly improved
      the accuracy of prediction. Results indicate that the DE content of lupins varies
      by up to 2.4 MJ/kg and that the DE content can be predicted with a good degree of
      accuracy using physical and chemical characteristics.

PMID- 19395517
TI  - Developmental changes in the concentrations of glutamine and other amino acids in
      plasma and skeletal muscle of the Standardbred foal.
AB  - Glutamine is concentrated within skeletal muscle, where it has been proposed to
      play a regulatory role in maintaining protein homeostasis. The work presented
      here addressed the hypothesis that glutamine would be the most abundant free
      alpha-AA in plasma and skeletal muscle in the foal during the first year of life.
      Glycine, however, was the most abundant free alpha-AA in plasma at birth and
      between 3 and 12 mo of age. The concentration of glutamine, the second most
      abundant AA at birth, increased through the first 7 d (P < 0.05) and then
      returned to values similar to those at birth. This resulted in glutamine being
      the most abundant free alpha-AA in plasma from 1 d through 1 mo of age. The most
      abundant free alpha-AA in skeletal muscle at birth was glutamine, but the
      concentration fell by more than 50% by d 15 and continued to decrease, reaching
      about one-third of the original values by 1 yr of age (P < 0.05). Glutamine
      synthetase was barely detectable in skeletal muscle at birth, but the abundance
      increased rapidly within 15 d of birth. The concentration of glycine, the second
      most abundant alpha AA in muscle at birth, decreased by about 40% by d 15 (P <
      0.05) and then stabilized at this value throughout the year. In contrast,
      glutamate, alanine, and serine concentrations, the third, fourth, and fifth most
      abundant free alpha-AA in muscle at birth, respectively, increased to new stable
      concentrations between 3 and 6 mo of age (P < 0.05). This resulted in alanine
      being the most abundant free alpha-AA in skeletal muscle at 12 mo of age,
      followed by glutamate, glutamine, and glycine. The decrease in intramuscular
      glutamine content, particularly during the first 2 wk after birth, is not
      compatible with a regulatory role for glutamine in muscle protein synthesis
      because it occurred at the time of maximum growth in these animals. The findings
      that, at certain times of development, glutamine was not the most abundant free
      alpha-AA in the foal is novel and signifies that intramuscular glutamine may have
      functions specific to muscle type and mammalian species.

PMID- 19395518
TI  - Effects of dietary supplementation with different forms of flax in late-gestation
      and lactation on fatty acid profiles in sows and their piglets.
AB  - The impact of feeding flax as seed, meal, or oil to late-pregnant and lactating
      sows on fatty acid profiles in sows and their piglets was studied. Sixty second-
      and third-parity sows (Yorkshire x Landrace) were fed 1 of 4 diets from 68 d of
      gestation until 21 d of lactation. Diets were: control without flax (CTL, n =
      15); 10% flaxseed supplementation (FS, n = 16); 6.5% flaxseed meal
      supplementation (FSM, n = 14); and 3.5% flaxseed oil supplementation (FSO, n =
      15). All diets were isonitrogenous and isocaloric. Jugular blood samples were
      obtained from sows on d 62 and 110 of gestation and on d 2 and 21 of lactation.
      Milk samples were obtained on d 3 and 20 of lactation. Fatty acid profiles were
      established in plasma and milk. One piglet per litter was slaughtered on d 1 for
      determination of fatty acid profiles in carcass and brain tissue. On d 110 of
      gestation, sows fed FS and FSO had less SFA (P < 0.05), more PUFA (P < 0.001),
      more n-3 fatty acids (P < 0.001), and a decreased n-6/n-3 ratio (P < 0.001) in
      their serum than sows fed FSM. These same differences were present on d 21 of
      lactation with a decrease in MUFA also being observed (P < 0.05). Milk from sows
      fed FS and FSO showed increased n-3 fatty acids (P < 0.01) and decreased n-6/n-3
      ratio (P < 0.001) on d 3 and 20 of lactation, as well as less SFA (P < 0.01) and
      MUFA (P < 0.05) and greater PUFA (P < 0.001) concentrations on d 20. Carcass and
      brain tissues from their newborn piglets also exhibited increased n-3 fatty acids
      (P < 0.001) and decreased n-6/n-3 ratio (P < 0.01) compared with piglets farrowed
      by sows fed FSM. Results demonstrated that feeding flax as seed or oil has
      significant effects on the fatty acid profile in sows and their offspring and
      that these changes are due to the oil content of flax because they were not
      observed when sows were fed FSM.

PMID- 19395519
TI  - Responses of pigs to Aspergillus niger phytase supplementation of low-protein or
      high-phytin diets.
AB  - Growth and N utilization responses of pigs to Aspergillus niger phytase
      supplementation of low-protein or high-phytin diets were examined in 2
      experiments. In the first experiment, 6 diets arranged in a 3 x 2 factorial with
      Aspergillus niger phytase at 0, 600, or 1,200 units/kg and dietary protein at 160
      or 200 g/kg; and 12 pigs (growth) or 6 pigs (N utilization) per diet were used to
      test the hypothesis that phytase ameliorates dietary protein effects on growth
      and nutrient balance. In the second experiment, 4 diets arranged in a 2 x 2
      factorial of phytase at 0 or 1,200 units/kg and phytin P at 2.2 g/kg (3.2 g/kg of
      total P) or 3.9 g/kg (4.9 g/kg of total P); and 12 pigs (growth) or 8 pigs fitted
      with ileal T-cannulas in a replicated 4 x 4 Latin square (for ileal digestibility
      of AA) per diet were used to test the hypothesis that increased phytin depresses
      nutrient utilization and phytase addition ameliorates these effects. Whereas
      reduced dietary protein depressed (P < 0.001) BW gain and N utilization, phytase
      in low-protein diet did not alleviate these effects. Although phytase ameliorated
      phytin-induced reduction in ileal P digestibility (P < 0.001), this was not
      accompanied by any change in ileal AA digestibility. Given that phytase improved
      (P < 0.001) P, but not N utilization of diets fed in both studies, phytase
      induced improvement in BW gain of pigs fed low-phytin P diets is independent of
      changes in N utilization.

PMID- 19395520
TI  - Effect of dietary protein level on growth performance, indicators of enteric
      health, and gastrointestinal microbial ecology of weaned pigs induced with
      postweaning colibacillosis.
AB  - The effect of dietary CP level on performance, enteric health, and
      gastrointestinal microbial ecology of weaned pigs challenged with enterotoxigenic
      Escherichia coli (ETEC) K88 was investigated in a 14-d study. Forty weaned pigs
      (BW = 5.32 +/- 0.24 kg, mean +/- SD), housed 4 per pen, were randomly assigned to
      2 diets (5 pens/diet): 1) 22.5% CP or 2) 17.6% CP supplemented with AA. Diets
      contained the same amount of ME and standardized ileal digestible Lys, Met + Cys,
      Thr, and Trp based on the ideal protein ratio. Isoleucine and Val were added to
      the 17.6% CP diet up to the level in the 22.5% CP diet. On d 8 postweaning, pigs
      were challenged with 6 mL of ETEC suspension (10(10) cfu/mL) by gavage. Feed
      disappearance and BW were measured on d 7, 9, 10, 12, and 14 for determination of
      ADG, ADFI, and G:F. One pig from each pen was serially slaughtered on -1, 3, and
      7 d postchallenge (10 pigs/d of slaughter) to evaluate gut morphology, and gut
      microbial ecology and metabolites. Pigs fed the 22.5% CP diet had greater (P <
      0.05) ADG and G:F than those fed the 17.6% CP diet before infection, but
      performance was similar between the 2 diets after ETEC challenge and overall. On
      d 3 after challenge, ETEC was not detected in the ileal digesta of pigs fed the
      17.6% CP diet but was detected in the ileal digesta of 80% of pigs fed the 22.5%
      CP diet (5.22 +/- 1.07 cfu/g, mean +/- SD). Pigs fed the 17.6% CP diet had a
      greater (P < 0.01) prevalence of order Clostridiales (73 vs. 50%), family
      Lachnospiraceae (43 vs. 18%), and genus Roseburia (13 vs. 3%) in the colon
      digesta 7 d after challenge compared with those fed the 22.5% CP diet. The
      richness and diversity of bacteria in the colon digesta were less (P < 0.05) in
      pigs fed the 17.6% CP diet than in those fed the 22.5% CP diet at -1, 3, and 7 d
      postchallenge. Pigs fed the 22.5% CP diet had greater (P < 0.05) ammonia N
      concentration in the colon digesta on -1 and 7 d after challenge compared with
      those fed the 17.6% CP diet. Pigs fed the 22.5% CP diet had deeper (P < 0.05)
      crypts 1 d before challenge, shorter villi 3 d after challenge, and reduced
      villus height:crypt depth 1 d before and 3 d after challenge compared with those
      fed the 17.6% CP diet. In conclusion, a reduction in the dietary CP level of
      weaned pigs from 22.5 to 17.6% with AA supplementation impaired growth
      performance before, but not after, the ETEC challenge and increased the relative
      composition of butyrate producing bacteria in the colon digesta after ETEC
      challenge.

PMID- 19395521
TI  - Metabolic fate of fatty acids involved in ruminal biohydrogenation in sheep fed
      concentrate or herbage with or without tannins.
AB  - A 2 x 2 factorial experiment was carried out to evaluate the effect of herbage or
      concentrate feeding and dietary tannin supplementation on fatty acid metabolism
      and composition in sheep ruminal fluid, plasma, and intramuscular fat. Twenty
      eight male lambs were divided into 2 equal groups at 45 d of age and kept in
      individual pens. One group was given exclusively fresh herbage (vetch), and the
      other group was fed a concentrate-based diet. Within each treatment, one-half of
      the lambs received supplementation of quebracho powder, providing 4.0% of dietary
      DM as tannins. Before slaughter, blood samples were collected. The animals were
      slaughtered at 105 d of age, and ruminal contents and LM were collected. Blood
      plasma, ruminal fluid, and LM fatty acid composition was determined by gas
      chromatography. Tannin supplementation reduced (P < 0.05) the concentration of
      stearic acid (-49%) and increased the concentration of vaccenic acid (+97%) in
      ruminal fluid from concentrate-fed lambs. Within concentrate- and herbage-based
      diets, tannin supplementation reduced the accumulation of SFA in blood (P < 0.05)
      compared with lambs fed the tannin-free diets. When tannins were included in the
      concentrate, the LM contained 2-fold greater concentrations of rumenic acid
      compared with the LM of the lambs fed the tannin-free concentrate (0.96 vs. 0.46%
      of total extracted fatty acids, respectively; P < 0.05). The concentration of
      PUFA was greater (P < 0.05) and SFA (P < 0.01) less in the LM from lambs fed the
      tannin-containing diets as compared with the animals receiving the tannin-free
      diets. These results confirm, in vivo, that tannins reduce ruminal
      biohydrogenation, as previously reported in vitro. This implies that tannin
      supplementation could be a useful strategy to increase the rumenic acid and PUFA
      content and to reduce the SFA in ruminant meats. However, the correct dietary
      concentration of tannins should be carefully chosen to avoid negative effects on
      DMI and animal performance.

PMID- 19395522
TI  - Grazing behavior and energy costs of activity: a comparison between two types of
      cattle.
AB  - The grazing behavior, diet intake, and energy costs of activity of 2 types of
      cows grazing a Mediterranean pasture were compared. Fifteen large-frame
      Beefmaster x Simford (BM) cross cows and 13 small Baladi (Ba) mature cows were
      allocated to the paddock and monitored during 3 seasons throughout 2006; spring
      (April), summer (June), and autumn (September). Cows were not given supplemental
      feed during the spring and summer, but had free access to a poultry litter
      supplement (25% CP, DM basis) during the autumn. Fecal output and digesta
      kinetics and feed intake were estimated using indigestible double-marker
      technique. Cows were fitted for 3 to 4 d in each season with global positioning
      system (GPS) monitors, with activity monitors attached to one of their hind legs,
      and with heart rate (HR) monitors harnessed to their chests. Oxygen consumption
      per heart beat was determined for each cow during each season to enable
      conversion of the diurnal HR patterns to heat production (HP) units. All the GPS
      data of cattle locations and the activity, HR, and HP data were synchronized to
      produce a simultaneous record at 5-min intervals. Partition of time spent by the
      cows lying down, standing, grazing, and walking without grazing, the horizontal
      and vertical distances walked per day, and the number of steps taken per day were
      summed from these records. Multiple regression models were adjusted to refer
      these activities to the HP and to estimate the specific HP costs per unit of each
      activity. Accordingly, the daily energy costs of activity were calculated for the
      2 cattle breeds on each season as the product of the specific activity and the
      number of units of each activity per day. Feed intake by Ba cows per unit of
      metabolic BW was greater (P < 0.001) than that of BM cows in both spring and
      summer and their apparent selection of greater-quality herbage in spring was
      greater (P < 0.1) than that of BM cows. The smaller framed Ba cows grazed more
      hours per day and walked longer distances than the BM cows among all seasons. The
      specific costs for locomotion were less for the Ba cows.

PMID- 19395523
TI  - Assessment of very long-chain fatty acids as complementary or alternative natural
      fecal markers to n-alkanes for estimating diet composition of goats feeding on
      mixed diets.
AB  - This study aimed to assess the use of very long-chain fatty acids (VLCFA) as an
      alternative or a complement to n-alkane markers for estimation of diet
      composition of goats fed 7 different diets, composed of different proportions of
      herbaceous (Lolium perenne and Trifolium repens) and heathland woody species
      (Erica umbellata, Erica cinerea, Calluna vulgaris, Erica arborea, and Ulex
      gallii), in a metabolism study. Diet composition was estimated from VLCFA (i.e.,
      C(22) to C(34)) and alkane (i.e., C(25) to C(33)) concentrations in diet and
      feces, by least squares procedures. For all plant species VLCFA concentrations
      were greater than their alkane concentrations, especially for the herbaceous
      species and U. gallii. In general, fecal recovery of both markers was incomplete
      and increased in a curvilinear (P < 0.001) fashion with carbon-chain length. The
      plants comprising the diets had a significant effect (P < 0.001) on fecal
      recovery of VLCFA and alkanes. Diet composition estimates based on VLCFA alone
      were less accurate (P = 0.013) than those obtained using alkanes alone.
      Combination of VLCFA and alkane data resulted in the most accurate (P < 0.05)
      estimates, indicating an increase on the discriminatory power among plant
      species. Use of uncorrected fecal marker concentrations provided the poorest
      estimates of diet composition, and use of individual recovery data and mean fecal
      recovery data of the dietary treatment yielded the most accurate ones. Results
      obtained in this study show that VLCFA have potential to be used as diet
      composition markers along with alkanes.

PMID- 19395524
TI  - The brain network underlying serial visual search: comparing overt and covert
      spatial orienting, for activations and for effective connectivity.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate the brain
      basis of overt and covert forms of attention during search, while employing
      stringent control of both eye movements and attentional shifts. A factorial
      design compared overt and covert forms of goal-directed serial search versus
      stimulus-driven tracking. To match ocular changes and the number and magnitude of
      attention shifts across cells in the design, stimulus-driven tracking involved
      trial-specific "replay" of previous goal-directed eye movements. We found that,
      in terms of cortical activations, engagement of the dorsal fronto-parietal
      network by goal-directed attention did not depend on oculomotor requirements,
      being found similarly for covert attention, in accord with other work. However,
      analyses of effective connectivity (or "functional coupling") revealed that
      information flow within this network changed significantly as a function of both
      the task (goal-directed or stimulus-driven) and the overt versus covert form of
      attention. Additionally, we observed a distinct set of subcortical regions
      (pulvinar and caudate nucleus) engaged primarily during the covert form of goal
      directed search. We conclude that dynamics within the dorsal fronto-parietal
      attentional system flexibly reorganize to integrate task demands and oculomotor
      requirements.

PMID- 19395525
TI  - Connections of auditory and visual cortex in the prairie vole (Microtus
      ochrogaster): evidence for multisensory processing in primary sensory areas.
AB  - In prairie voles, primary sensory areas are dominated by neurons that respond to
      one sensory modality, but some neurons also respond to stimulation of other
      modalities. To reveal the anatomical substrate for these multimodal responses, we
      examined the connections of the primary auditory area + the anterior auditory
      field (A1 + AAF), the temporal anterior area (TA), and the primary visual area
      (V1). A1 + AAF had intrinsic connections and connections with TA, multimodal
      cortex (MM), V1, and primary somatosensory area (S1). TA had intrinsic
      connections and connections with A1 + AAF, MM, and V2. Callosal connections were
      observed in homotopic locations in auditory cortex for both fields. A1 + AAF and
      TA receive thalamic input primarily from divisions of the medial geniculate
      nucleus but also from the lateral geniculate nucleus (LGd), the lateral posterior
      nucleus, and the ventral posterior nucleus (VP). V1 had dense intrinsic
      connections and connections with V2, MM, auditory cortex, pyriform cortex (Pyr),
      and, in some cases, somatosensory cortex. V1 had interhemispheric connections
      with V1, V2, MM, S1, and Pyr and received thalamic input from LGd and VP. Our
      results indicate that multisensory integration occurs in primary sensory areas of
      the prairie vole cortex, and this may be related to behavioral specializations
      associated with its niche.

PMID- 19395526
TI  - An fMRI study of functional abnormalities in the verbal working memory system and
      the relationship to clinical symptoms in chronic schizophrenia.
AB  - There has been evidence for functional abnormalities of the verbal working memory
      system in schizophrenia. Verbal working memory crucially involves the interplay
      between the anterior and posterior language systems, and previous studies have
      shown converging evidence for abnormalities in the posterior language system in
      schizophrenia. In this functional magnetic resonance imaging study, we measured
      cortical activity in chronic schizophrenic patients and matched healthy controls
      during auditory and visual verbal working memory tasks. We employed 1) regional
      analyses specifically targeting the posterior language system and 2) analyses of
      functional connectivity between anterior and posterior language regions. We
      performed these analyses separately for each memory stage and modality. In the
      regional analyses, the left sylvian-parietal-temporal (Spt) area consistently
      showed reduced activation during encoding and retrieval stages in schizophrenia.
      Magnitudes of activation in the left posterior superior temporal sulcus were
      correlated with the severity of delusions at every memory stage. Functional
      connectivity analyses revealed reduced connectivity between the left Spt and the
      anterior insula during the encoding of auditory words. In addition, the
      connectivity strength was correlated with the severity of auditory
      hallucinations. These findings identify abnormal components in the verbal working
      memory system and illustrate their possible overlap with the mechanisms of core
      schizophrenic symptoms.

PMID- 19395527
TI  - Dual mechanisms for the cross-sensory spread of attention: how much do learned
      associations matter?
AB  - The spread of attention-related processing across anatomically separated cortical
      regions plays an important role in the binding of an object's features, both
      within and across sensory modalities. We presented multiple exemplars of
      semantically congruent multisensory objects (e.g., dogs with barks) and
      semantically incongruent multisensory objects (e.g., guitars with barks) while
      recording high-density event-related potentials and tested whether highly learned
      associations among the multisensory features of well-known objects modulated the
      spread of attention from an attended visual stimulus to its paired, task
      irrelevant sound. Our findings distinguish dual mechanisms for the cross-sensory
      spread of attention: 1) a stimulus-driven spread of attention that occurs
      whenever a task-irrelevant sound is simultaneously presented with an attended
      visual stimulus, independent of highly learned associations, and 2) a
      representation-driven spread of attention that occurs in response to a task
      irrelevant sound that is semantically congruent with a visual target and is
      therefore dependent on highly learned associations. The first mechanism is
      thought to reflect bottom-up feature binding, whereas the second mechanism is
      thought to reflect the top-down activation of a stored object representation that
      includes the well-known object's multisensory features. When a semantically
      congruent, task-irrelevant sound is simultaneously presented with a well-known
      visual target, the combined spread of attention through both mechanisms appears
      additive.

PMID- 19395528
TI  - New and improved tools for in utero electroporation studies of developing
      cerebral cortex.
AB  - In utero electroporation (IUE) has become a method of choice for rapid gain and
      loss of function studies in embryonic cerebral cortex. In this review we
      highlight some of the proven and recent advances in IUE technology that make it
      applicable to an increasingly wide array of experiments requiring spatial and
      temporal control of gene expression. Recently, cell-type-specific promoters and
      tamoxifen-gated cre-recombinase have been shown to work effectively with IUE.
      Experiments can now be designed and carried out to test whether and which cell
      type-specific mechanisms operate within defined periods of neuronal migration and
      maturation. We have recently adapted this conditional expression approach to
      implement conditional rescue experiments. In conditional rescue, expression of an
      RNA interference (RNAi) target is restored by tamoxifen-induced cre-mediated
      recombination. An initial disruption in migration, and resultant malformation,
      caused by DCX RNAi was reversed by delayed re-expression of Dcx. In the future,
      combinations of spatially directed, cell-type-specific, and tamoxifen-gated
      transgene expression can be used to address the complex mechanisms likely to
      operate during development of cerebral cortex.

PMID- 19395529
TI  - Wireless infrared thermometer in the follow-up of finger temperatures.
AB  - After replantation surgery it is helpful to use temperature monitoring in order
      to detect vascular problems early. One of the methods currently employed is to
      use a thermometer with a wired probe attached to the tissue being monitored. An
      infrared wireless thermometer, commonly used in industry, measures temperatures
      of surfaces without actually touching them. The purpose of this study was to
      evaluate the efficacy of infrared wireless thermometer technology for monitoring
      finger temperature. Finger temperatures of 38 volunteers were measured using the
      infrared wireless thermometer. A traditional wired thermometer was used as
      control. The measurements of both thermometers were similar when the temperature
      was 31.5 degrees and over, with no statistical differences (mean difference 0.06
      degrees , P=0.521). At lower temperatures, however, the wireless infrared
      thermometer showed slightly lower temperature values (mean difference 1.01
      degrees , P<0.001). There was no difference between the finger temperatures of
      smokers and non-smokers. There is potential for the wireless infrared thermometer
      to be used as an easier alternative to the traditional wired thermometer in
      monitoring temperatures of revascularised or replanted parts including digital
      replants. Further clinical studies would be warranted.

PMID- 19395531
TI  - Age is an important predictor of short-term outcome in endoscopic carpal tunnel
      release.
AB  - Endoscopic carpal tunnel release is a minimally invasive technique that may
      reduce sick leave and facilitate postoperative rehabilitation and short-term
      outcome. The aim of this study was to investigate the influence of age as a
      predictor of short-term outcome in endoscopic carpal tunnel release. We did a
      prospective registration of patient satisfaction, symptoms and function before
      and 2-months after endoscopic carpal tunnel release in 101 consecutive patients
      aged 23-94 years and then submitted the data to multivariable logistic regression
      analysis. Patient age >65 years was a good predictor of a less favourable short
      term outcome, and endoscopic carpal tunnel release may not be justified as a
      routine procedure in elderly patients.

PMID- 19395533
TI  - Bilateral hand transplantation: result at 20 months.
AB  - On November 2006, a bilateral hand allotransplantation was performed for a 47
      year-old female who had suffered radiocarpal amputations 28 years before.
      Technical aspects of the operation are detailed. Alemtuzumab induction, and
      triple therapy of tacrolimus, mycophenolate mofetil and prednisone were used to
      control rejection. The evolution of the result and functioning at 20 months are
      presented in detail. Two acute rejection episodes occurred and were successfully
      treated with steroids. In addition the patient developed a factitious visual
      disorder and a facial basal cell carcinoma. Functionally, at 20 months, the
      patient had a Hand Registry Functional Score of 69 (good), and a DASH score of
      19.

PMID- 19395535
TI  - The partial excision greenstick (PEG) osteotomy: a novel approach to the
      correction of clinodactyly in children's fingers.
AB  - Closing wedge osteotomy is an accepted technique for correcting bony
      malalignment. This study reports the results of a novel osteotomy technique used
      in children's hands. Excision of a partial wedge generates a 'greenstick' type of
      fracture which can then be reduced and stabilised using only intraosseous wires.
      Eight consecutive patients who underwent surgery of this type between March 2003
      and January 2008 were reviewed retrospectively. Union was obtained in all cases
      and there was good bone alignment and range of movement. No significant technique
      related complications were encountered. This approach is a simple and effective
      way of correcting malalignment in the small bones of children's hands.

PMID- 19395539
TI  - Flexor pollicis longus tendon ruptures after palmar plate fixation of fractures
      of the distal radius.
AB  - Palmar plate fixation of distal radial fractures is becoming a standard treatment
      for this common injury. Ruptures of the extensor pollicis longus tendon have been
      reported in 8.6% of cases after this procedure. Although palmar plate fixation
      has also been associated with flexor pollicis longus (FPL) tendon problems, the
      majority of reported cases pre-date the use of newer anatomically precontoured
      locking plates. In this paper seven cases of FPL rupture are presented. This
      complication does not appear to be unique to one type of implant. The possible
      aetiologies for FPL ruptures are discussed and ways to reduce the incidence of
      this complication are suggested.

PMID- 19395540
TI  - Redefining the Scl-70 indirect immunofluorescence pattern: autoantibodies to DNA
      topoisomerase I yield a specific compound immunofluorescence pattern.
AB  - OBJECTIVES: To report on a novel IIF pattern specifically associated with
      antibodies to DNA topo I. METHODS: A novel compound IF pattern, designated Scl-70
      pattern, was characterized in routine ANA-HEp-2 IIF screening. Within the last 3
      years, all serum samples presenting the Scl-70 pattern at the ANA-HEp2 IIF
      screening were tested for anti-topo I reactivity. Conversely, 16 serum samples
      with known anti-topo I reactivity and affinity-purified anti-topo I antibody
      preparations were tested for the Scl-70 pattern. RESULTS: The Scl-70 pattern
      comprised the staining of five cellular regions: nucleus, nucleolus and cytoplasm
      in interphase cells; nucleolar organizing region (NOR) and chromosomes in mitotic
      cells. All 81 serum samples selected as Scl-70 pattern reacted with topo I. All
      16 anti-topo I samples and antibody preparations reproduced the Scl-70 pattern.
      This compound IF pattern was consistently observed in different commercial HEp-2
      cell slides and in home-made slides with HEp-2 cells and human fibroblasts fixed
      with alternative protocols. Double IIF experiments demonstrated the co
      localization of topo I and human upstream binding factor at the NOR. CONCLUSIONS:
      The Scl-70 pattern belongs to the group of compound IF patterns that hold strong
      association with the respective autoantibody specificities, such as that observed
      with centromere protein F (CENP-F) and nuclear mitotic apparatus-1 (NuMA-1)
      protein. The identification of the Scl-70 pattern at routine ANA-HEp-2 IIF
      screening may lead to implementation of specific tests for the identification of
      anti-topo I antibodies. In addition, the Scl-70 pattern outlines cellular domains
      other than those previously reported for topo I, which is of interest for further
      understanding the roles of this enzyme in cell biology.

PMID- 19395541
TI  - Association of TLR4 polymorphisms with Behcet's disease in a Korean population.
AB  - OBJECTIVES: HLA-B51 is strongly associated with Behcet's disease (BD) in any
      ethnic background. We recently reported that another gene, Toll-like receptor-4
      (TLR4) is also implicated in BD in a Japanese population. To confirm these
      results, we investigated polymorphisms in the TLR4 gene in Korean patients with
      BD. METHODS: In this study, 119 patients with BD and 141 healthy controls were
      enrolled; every participant was a Korean. Nine single nucleotide polymorphisms
      previously detected in TLR4 by direct sequencing were analysed for an association
      with BD. RESULTS: The most frequent haplotype, TAGCGGTAA, was significantly
      increased in HLA-B*51-positive BD patients (49.5%), compared with healthy control
      participants [32.3%; P = 0.029; odds ratio (OR) = 2.01; 95% CI 1.25-3.23]. This
      haplotype was also significantly increased in BD patients with arthritis (48.2%;
      P = 0.003; OR = 1.96; 95% CI 1.26-3.26). There were no significant differences in
      the allele and genotype frequencies of patients and controls for each single
      nucleotide polymorphism. CONCLUSIONS: The haplotype of TLR4 may increase the risk
      for developing BD and the complication of arthritis in the Korean population.

PMID- 19395542
TI  - The BILAG-2004 index is sensitive to change for assessment of SLE disease
      activity.
AB  - OBJECTIVE: To determine if the BILAG-2004 index is sensitive to change for
      assessment of SLE disease activity. METHODS: This was a prospective multi-centre
      longitudinal study of SLE patients. At every assessment, data were collected on
      disease activity (BILAG-2004 index) and treatment. Analyses were performed using
      overall BILAG-2004 index score (as determined by the highest score achieved by
      any of the individual systems) and all the systems scores. Sensitivity to change
      was assessed by determining the relationship between change in disease activity
      and change in therapy between two consecutive visits. Statistical analyses were
      performed using multinomial logistic regression. RESULTS: There were 1761
      assessments from 347 SLE patients that contributed 1414 observations for
      analysis. An increase in therapy between visits occurred in 22.7% observations,
      while 37.3% had a decrease in therapy and in 40.0% therapy was unchanged.
      Increase in overall BILAG-2004 index score was associated with increase in
      therapy and inversely associated with decrease in therapy. Decrease in overall
      BILAG-2004 index score was associated with decrease in therapy and was inversely
      associated with increase in therapy. Changes in overall BILAG-2004 index score
      were differentially related to change in therapy, with greater change in score
      having greater predictive power. Increase in the scores of most systems was
      independently associated with an increase in treatment and there was no
      significant association between decreases in the score of any system with an
      increase in therapy. CONCLUSIONS: The BILAG-2004 index is sensitive to change and
      is suitable for use in longitudinal studies of SLE.

PMID- 19395543
TI  - Paradoxical adverse events of anti-tumour necrosis factor therapy for
      spondyloarthropathies: a retrospective study.
AB  - OBJECTIVES: Several paradoxical adverse events (PAEs), e.g. IBDs, acute anterior
      uveitis (AAU) and psoriasis, have been described in patients taking anti-TNF
      drugs. This retrospective study aimed to describe the different PAEs that have
      occurred in a population of SpA patients treated with anti-TNF drugs, and to
      determine whether they are drug specific. METHODS: Since 2000, we have followed
      296 patients with SpA [198 AS, 21 SpA associated with IBD (9 ulcerative colitis,
      12 Crohn's disease) and 77 psoriatic arthritis] treated with at least one anti
      TNF drug (infliximab, etanercept or adalimumab), and 112 SpA patients treated
      only with conventional DMARDs who served as controls. Considering the cumulative
      time of exposure to each anti-TNF agent, the frequencies of new-onset PAEs in
      exposed patients were calculated. RESULTS: Respective cumulative exposure times
      were 287, 290 and 62 patient-years for infliximab, etanercept and adalimumab. We
      observed the following PAEs: five psoriasis (three under infliximab and one with
      etanercept or adalimumab), three AAU (1/100 patient-years, all under etanercept)
      and four IBD (three under etanercept and one under infliximab). There was no
      significant association among any of these PAEs and a specific anti-TNF agent;
      nor significant difference in the overall PAEs among patients receiving anti-TNF
      drugs or controls (P = 0.303), the latter experiencing two psoriasis and three
      AAU. CONCLUSIONS: Undesirable side effects--IBD, AAU and psoriasis--may appear
      with anti-TNF drugs. Even if they are, a priori, paradoxical, no evidence
      supports any PAEs to be anti-TNF agent-specific in SpA.

PMID- 19395544
TI  - Evaluation of composite measures of treatment response without acute-phase
      reactants in patients with rheumatoid arthritis.
AB  - OBJECTIVES: To evaluate composite measures of response without acute-phase
      reactants in RA patients. Specifically, Clinical Disease Activity Index (CDAI)
      derived response criteria were compared with the European League Against
      Rheumatism (EULAR) response criteria, and the modified ACR (mACR) response
      criteria were compared to the ACR response criteria. METHODS: Data from 10 108 RA
      patients enrolled in the Consortium of Rheumatology Researchers of North America
      registry were examined, including 649 patients initiating DMARD therapy. CDAI cut
      off points for disease activity levels and responses were derived using receiver
      operating characteristic curves with the DAS28 and EULAR response criteria as
      gold standards. The kappa-statistics were applied to assess agreement between
      CDAI-derived and EULAR-defined responses, as well as ACR20 and ACR50 with mACR20-
      and mACR50-defined responses, respectively. RESULTS: For the components of the
      EULAR response, the derived CDAI cut-off points for DAS28 levels of 3.2 and 5.1
      were 7.6 and 19.6, respectively. The derived CDAI cut-off points were 4.3 and
      10.0 for DAS28 changes of 0.6 and 1.2, respectively. There were moderate to
      substantial agreements between CDAI-derived and EULAR responses (kappa = 0.57
      0.71). Agreement of ACR20 and ACR50 with mACR20 and mACR50 responses,
      respectively, was excellent (kappa = 0.88-0.95). CONCLUSIONS: Agreement between
      composite measures of response without acute-phase reactants and standard
      measures ranged from moderate to excellent. The mACR20 and mACR50 criteria as
      well as CDAI-derived response criteria, can serve as composite measures of
      response in clinical practice and research settings without access to acute-phase
      reactants.

PMID- 19395545
TI  - Nonmyofilament-associated troponin T fragments induce apoptosis.
AB  - Troponin T (TnT) is a striated muscle-specific protein and an abundant component
      of the myofilaments. Nonmyofilament-associated TnT is rapidly degraded in
      myocytes, implying an importance in the maintenance of the cellular environment.
      However, if the level of nonmyofilament-associated TnT or TnT fragments exceeds
      the degradation capacity, it may cause cytotoxicity. To investigate this
      hypothesis, we constructed bicistronic vectors to express different portions of
      TnT polypeptide chain, together with nonfusion green fluorescent protein as a
      tracer for the transfection. Cytotoxicity of the TnT fragments was studied
      through forced expression in C(2)C(12) myoblasts and human embryonic kidney-293
      nonmuscle cells and examination of the viability of the transfected cells. The
      results demonstrated that, in the absence of myofilaments, the conserved COOH
      terminal and middle fragments of TnT were highly effective on inducing cell death
      via apoptosis, whereas the NH(2)-terminal variable region was not. As combined
      effects, nonmyofilament-associated intact cardiac TnT and a COOH-terminal
      truncated slow TnT fragment found in Amish nemaline myopathy exhibited
      intermediate cytotoxicity. A particular significance of this finding is that peak
      releases of TnT or TnT fragments from decomposition of a large number of
      myofibrils in acute myocardial infarction may breach the cellular protection of
      proteolytic degradation and result in apoptosis as a potential cause for the loss
      of cardiomyocytes.

PMID- 19395546
TI  - Recombinant human activated protein C improves endotoxemia-induced endothelial
      dysfunction: a blood-free model in isolated mouse arteries.
AB  - Recombinant human activated protein C (rhAPC) is one of the treatment panels for
      improving vascular dysfunction in septic patients. In a previous study, we
      reported that rhAPC treatment in rat endotoxemia improved vascular reactivity,
      although the mechanisms involved are still under debate. In the present study, we
      hypothesized that rhAPC may improve arterial dysfunction through its
      nonanticoagulant properties. Ten hours after injection of LPS in mice (50 mg/kg
      ip), aortic rings and mesenteric arteries were isolated and incubated with or
      without rhAPC for 12 h. Aortic rings were mounted in a myograph, after which
      arterial contractility and endothelium-dependent relaxation were measured in the
      presence or absence of nitric oxide synthase or cyclooxygenase inhibitors. Flow
      (shear stress)-mediated dilation with or without the above inhibitors was also
      measured in mesenteric resistance arteries. Protein expression was assessed by
      Western blotting. Lipopolysaccharide (LPS) reduced aortic contractility to KCl
      and phenylephrine as well as dilation to acetylcholine. LPS also reduced flow
      mediated dilation in mesenteric arteries. In rhAPC-treated aorta and mesenteric
      arteries, contractility and endothelial responsiveness to vasodilator drug and
      shear stress were improved. rhAPC treatment also improved LPS-induced endothelial
      dysfunction; this effect was associated with an increase in the phosphorylated
      form of endothelial nitric oxide synthase and protein kinase B as well as
      cyclooxygenase vasodilatory pathways, thus suggesting that these pathways,
      together with the decrease in nuclear factor-kappaB activation and inducible
      nitric oxide synthase expression in the vascular wall, are implicated in the
      endothelial effect of rhAPC. In conclusion, ex vivo application of rhAPC improves
      arterial contractility and endothelial dysfunction resulting from endotoxemia in
      mice. This finding provides important insights into the mechanism underlying
      rhAPC-induced improvements on arterial dysfunction during septic shock.

PMID- 19395547
TI  - Clinical assessment of left ventricular rotation and strain: a novel approach for
      quantification of function in infarcted myocardium and its border zones.
AB  - Left ventricular (LV) circumferential strain and rotation have been introduced as
      clinical markers of myocardial function. This study investigates how regional LV
      apical rotation and strain can be used in combination to assess function in the
      infarcted ventricle. In healthy subjects (n = 15) and patients with myocardial
      infarction (n = 23), LV apical segmental rotation and strain were measured from
      apical short-axis recordings by speckle tracking echocardiography (STE) and MRI
      tagging. Infarct extent was determined by late gadolinium enhancement MRI. To
      investigate mechanisms of changes in strain and rotation, we used a mathematical
      finite element simulation model of the LV. Mean apical rotation and strain by STE
      were lower in patients than in healthy subjects (9.0 +/- 4.9 vs. 12.9 +/- 3.5
      degrees and -13.9 +/- 10.7 vs. -23.8 +/- 2.3%, respectively, P < 0.05). In
      patients, regional strain was reduced in proportion to segmental infarct extent
      (r = 0.80, P < 0.0001). Regional rotation, however, was similar in the center of
      the infarct and in remote viable myocardium. Minimum and maximum rotations were
      found at the infarct borders: minimum rotation at the border zone opposite to the
      direction of apical rotation, and maximum rotation at the border zone in the
      direction of rotation. The simulation model reproduced the clinical findings and
      indicated that the dissociation between rotation and strain was caused by
      mechanical interactions between infarcted and viable myocardium. Systolic strain
      reflects regional myocardial function and infarct extent, whereas systolic
      rotation defines infarct borders in the LV apical region. Regional rotation,
      however, has limited ability to quantify regional myocardial dysfunction.

PMID- 19395548
TI  - Reductions in mitochondrial O(2) consumption and preservation of high-energy
      phosphate levels after simulated ischemia in chronic hibernating myocardium.
AB  - We performed the present study to determine whether hibernating myocardium is
      chronically protected from ischemia. Myocardial tissue was rapidly excised from
      hibernating left anterior descending coronary regions (systolic wall thickening =
      2.8 +/- 0.2 vs. 5.4 +/- 0.3 mm in remote myocardium), and high-energy phosphates
      were quantified by HPLC during simulated ischemia in vitro (37 degrees C). At
      baseline, ATP (20.1 +/- 1.0 vs. 26.7 +/- 2.1 micromol/g dry wt, P < 0.05), ADP
      (8.1 +/- 0.4 vs. 10.3 +/- 0.8 micromol/g, P < 0.05), and total adenine
      nucleotides (31.2 +/- 1.3 vs. 40.1 +/- 2.9 micromol/g, P < 0.05) were depressed
      compared with normal myocardium, whereas total creatine, creatine phosphate, and
      ATP-to-ADP ratios were unchanged. During simulated ischemia, there was a marked
      attenuation of ATP depletion (5.6 +/- 0.9 vs. 13.7 +/- 1.7 micromol/g at 20 min
      in control, P < 0.05) and mitochondrial respiration [145 +/- 13 vs. 187 +/- 11 ng
      atoms O(2).mg protein(-1).min(-1) in control (state 3), P < 0.05], whereas
      lactate accumulation was unaffected. These in vitro changes were accompanied by
      protection of the hibernating heart from acute stunning during demand-induced
      ischemia. Thus, despite contractile dysfunction at rest, hibernating myocardium
      is ischemia tolerant, with reduced mitochondrial respiration and slowing of ATP
      depletion during simulated ischemia, which may maintain myocyte viability.

PMID- 19395549
TI  - Determination of rate constants for turnover of myosin isoforms in rat
      myocardium: implications for in vivo contractile kinetics.
AB  - The ventricles of small mammals express mostly alpha-myosin heavy chain (alpha
      MHC), a fast isoform, whereas the ventricles of large mammals, including humans,
      express approximately 10% alpha-MHC on a predominately beta-MHC (slow isoform)
      background. In failing human ventricles, the amount of alpha-MHC is dramatically
      reduced, leading to the hypothesis that even small amounts of alpha-MHC on a
      predominately beta-MHC background confer significantly higher rates of force
      development in healthy ventricles. To test this hypothesis, it is necessary to
      determine the fundamental rate constants of cross-bridge attachment (f(app)) and
      detachment (g(app)) for myosins composed of 100% alpha-MHC or beta-MHC, which can
      then be used to calculate twitch time courses for muscles expressing variable
      ratios of MHC isoforms. In the present study, rat skinned trabeculae expressing
      either 100% alpha-MHC or 100% beta-MHC were used to measure ATPase activity,
      isometric force, and the rate constant of force redevelopment (k(tr)) in
      solutions of varying Ca(2+) concentrations. The rate of ATP utilization was
      approximately 2.5-fold higher in preparations expressing 100% alpha-MHC compared
      with those expressing only beta-MHC, whereas k(tr) was 2-fold faster in the alpha
      MHC myocardium. From these variables, we calculated f(app) to be approximately
      threefold higher for alpha-MHC than beta-MHC and g(app) to be twofold higher in
      alpha-MHC. Mathematical modeling of isometric twitches predicted that small
      increases in alpha-MHC significantly increased the rate of force development.
      These results suggest that low-level expression of alpha-MHC has significant
      effects on contraction kinetics.

PMID- 19395550
TI  - Endothelin receptor blockade combined with phosphodiesterase-5 inhibition
      increases right ventricular mitochondrial capacity in pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) is often treated with endothelin (ET)
      receptor blockade or phosphodiesterase-5 (PDE5) inhibition. Little is known about
      the specific effects on right ventricular (RV) function and metabolism. We
      determined the effects of single and combination treatment with Bosentan [an ET
      type A (ET(A))/type B (ET(B)) receptor blocker] and Sildenafil (a PDE5 inhibitor)
      on RV function and oxidative metabolism in monocrotaline (MCT)-induced PAH.
      Fourteen days after MCT injection, male Wistar rats were orally treated for 10
      days with Bosentan, Sildenafil, or both. RV catheterization and echocardiography
      showed that MCT clearly induced PAH. This was evidenced by increased RV systolic
      pressure, reduced cardiac output, increased pulmonary vascular resistance (PVR),
      and reduced RV fractional shortening. Quantitative histochemistry showed marked
      RV hypertrophy and fibrosis. Monotreatment with Bosentan or Sildenafil had no
      effect on RV systolic pressure or cardiac function, but RV fibrosis was reduced
      and RV capillarization increased. Combination treatment did not reduce RV
      systolic pressure, but significantly lowered PVR, and normalized cardiac output,
      RV fractional shortening, and fibrosis. Only combination treatment increased the
      mitochondrial capacity of the RV, as reflected by increased succinate
      dehydrogenase and cytochrome c oxidase activities, associated with an activation
      of PKG, as indicated by increased VASP phosphorylation. Moreover, significant
      interactions were found between Bosentan and Sildenafil on PVR, cardiac output,
      RV contractility, PKG activity, and mitochondrial capacity. These data indicate
      that the combination of Bosentan and Sildenafil may beneficially contribute to RV
      adaptation in PAH, not only by reducing PVR but also by acting on the
      mitochondria in the heart.

PMID- 19395551
TI  - Genetic influence on electrocardiogram time intervals and heart rate in aging
      mice.
AB  - Understanding the genetic influence on ECG time intervals and heart rate (HR) is
      important for identifying the genes underlying susceptibility to cardiac
      arrhythmias. The objective of this study was to determine the genetic influence
      on ECG parameters and their age-related changes in mice. ECGs were recorded in
      lead I on 8 males and 8 females from each of 28 inbred strains at the ages of 6,
      12, and 18 mo. Significant interstrain differences in the P-R interval, QRS
      complex duration, and HR were found. Age-related changes in the P-R interval, QRS
      complex duration, and HR differed among strains. The P-R interval increased with
      age in 129S1/SvlmJ females. The QRS complex duration decreased with age in
      C57BR/J males and DBA2/J females but increased in NON/ShiLtJ females. HR
      decreased in C57L/J females and SM/J and P/J males but increased in BALB/cByJ
      males. Differences between males and females were found for HR in SJL/J mice and
      in the P-R interval in 129S1/SvlmJ mice. Broad-sense heritability estimates of
      ECG time intervals and HR ranged from 0.31 for the QRS complex duration to 0.52
      for the P-R interval. Heritability estimates decreased with age for the P-R
      interval. Our study revealed that genetic factors play a significant role on
      cardiac conduction activity and age-related changes in ECG time intervals and HR.

PMID- 19395552
TI  - Role of oxidative stress and AT1 receptors in cerebral vascular dysfunction with
      aging.
AB  - Vascular dysfunction occurs with aging. We hypothesized that oxidative stress and
      ANG II [acting via ANG II type 1 (AT(1)) receptors] promotes cerebral vascular
      dysfunction with aging. We studied young (5-6 mo), old (17-19 mo), and very old
      (23 +/- 1 mo) mice. In basilar arteries in vitro, acetylcholine (an endothelium
      dependent agonist) produced dilation in young wild-type mice that was reduced by
      approximately 60 and 90% (P < 0.05) in old and very old mice, respectively.
      Similar effects were seen using A23187, a second endothelium-dependent agonist.
      The vascular response to acetylcholine in very old mice was almost completely
      restored with tempol (a scavenger of superoxide) and partly restored by PJ34, an
      inhibitor of poly(ADP-ribose) polymerase (PARP). We used mice deficient in Mn-SOD
      (Mn-SOD(+/-)) to test whether this form of SOD protected during aging but found
      that age-induced endothelial dysfunction was not altered by Mn-SOD deficiency.
      Cerebral vascular responses were similar in young mice lacking AT(1) receptors
      (AT(1)(-/-)) and wild-type mice. Vascular responses to acetylcholine and A23187
      were reduced by approximately 50% in old wild-type mice (P < 0.05) but were
      normal in old AT(1)-deficient mice. Thus, aging produces marked endothelial
      dysfunction in the cerebral artery that is mediated by ROS, may involve the
      activation of PARP, but was not enhanced by Mn-SOD deficiency. Our findings
      suggest a novel and fundamental role for ANG II and AT(1) receptors in age
      induced vascular dysfunction.

PMID- 19395553
TI  - ERM protein moesin is phosphorylated by advanced glycation end products and
      modulates endothelial permeability.
AB  - Advanced glycation end products (AGEs) accumulated in different pathological
      conditions have the potent capacity to alter cellular properties that include
      endothelial structural and functional regulations. The disruption of endothelial
      barrier integrity may contribute to AGE-induced microangiopathy and
      macrovasculopathy. Previous studies have shown that AGEs induced the
      rearrangement of actin and subsequent hyperpermeability in endothelial cells
      (ECs). However, the mechanisms involved in this AGE-evoked EC malfunction are not
      well understood. This study directly evaluated the involvement of moesin
      phosphorylation in AGE-induced alterations and the effects of the RhoA and p38
      MAPK pathways on this process. Using immortalized human dermal microvascular ECs
      (HMVECs), we first confirmed that the ezrin/radixin/moesin (ERM) protein moesin
      is required in AGE-induced F-actin rearrangement and hyperpermeability responses
      in ECs by knockdown of moesin protein expression with small interfering RNA. We
      then detected AGE-induced moesin phosphorylation by Western blot analysis. The
      mechanisms involved in moesin phosphorylation were analyzed by blocking AGE
      receptor binding and inhibiting Rho and MAPK pathways. AGE-treated HMVECs
      exhibited time- and dose-dependent increases in the Thr(558) phosphorylation of
      moesin. The increased moesin phosphorylation was attenuated by preadministrations
      of AGE receptor antibody, Rho kinase (ROCK), or p38 inhibitor. Suppression of p38
      activation via the expression of dominant negative mutants with Ad.MKK6b or
      Ad.p38alpha also decreased moesin phosphorylation. The activation of the p38
      pathway by transfection of HMVECs with an adenoviral construct of dominant active
      MKK6b resulted in moesin phosphorylation. These results suggest a critical role
      of moesin phosphorylation in AGE-induced EC functional and morphological
      regulations. Activation of the ROCK and p38 pathways is required in moesin
      phosphorylation.

PMID- 19395554
TI  - Cardiovascular responses to microinjections of urocortins into the NTS: role of
      inotropic glutamate receptors.
AB  - Urocortin 1 (Ucn1) and urocortin 3 (Ucn3) are new members of the corticotrophin
      releasing factor (CRF) peptide family. Ucn1 is a ligand for both the CRF type 1
      receptors (CRF(1)Rs) and the CRF type 2 receptors (CRF(2)Rs), whereas Ucn3 is a
      high-affinity ligand for the CRF(2)Rs. Recently, we reported that Ucn3
      microinjections into the medial nucleus tractus solitarius (mNTS) elicit
      decreases in mean arterial pressure (MAP) and heart rate (HR) (Nakamura T, Kawabe
      K, Sapru HN. Am J Physiol Heart Circ Physiol 296: H325-H332, 2009). The presence
      of CRF(2)Rs on afferent terminals has been reported in the mNTS of the rat. It
      was hypothesized that activation of CRF(2)Rs on afferent terminals in the mNTS
      may release glutamate, which, in turn, may elicit decreases in MAP and HR via
      activation of ionotropic glutamate receptors (iGLURs). This hypothesis was tested
      in urethane-anesthetized, artificially ventilated, adult male Wistar rats.
      Microinjections (100 nl) of Ucn1 (0.12 mM) into the mNTS elicited decreases in
      MAP and HR. The responses were partially blocked by microinjections of iGLUR
      antagonists into the mNTS. On the other hand, the decreases in MAP and HR
      elicited by microinjections of Ucn3 (0.06 mM) into the mNTS were completely
      blocked by microinjections of iGLUR antagonists into the mNTS. These results
      indicate that activation of CRF(2)Rs in the mNTS, by Ucn1 and Ucn3, releases
      glutamate, which, in turn, elicits decreases in MAP and HR via activation of
      iGLURs.

PMID- 19395555
TI  - Heart failure therapy mediated by the trophic activities of bone marrow
      mesenchymal stem cells: a noninvasive therapeutic regimen.
AB  - Heart failure carries a poor prognosis with few treatment options. While
      myocardial stem cell therapeutic trials have traditionally relied on
      intracoronary infusion or intramyocardial injection routes, these cell delivery
      methods are invasive and can introduce harmful scar tissue, arrhythmia,
      calcification, or microinfarction in the heart. Given that patients with heart
      failure are at an increased surgical risk, the development of a noninvasive stem
      cell therapeutic approach is logistically appealing. Taking advantage of the
      trophic effects of bone marrow mesenchymal stem cells (MSCs) and using a hamster
      heart failure model, the present study demonstrates a novel noninvasive
      therapeutic regimen via the direct delivery of MSCs into the skeletal muscle bed.
      Intramuscularly injected MSCs and MSC-conditioned medium each significantly
      improved ventricular function 1 mo after MSC administration. MSCs at 4 million
      cells/animal increased fractional shortening by approximately 40%, enhanced
      capillary and myocyte nuclear density by approximately 30% and approximately 80%,
      attenuated apoptosis by approximately 60%, and reduced fibrosis by approximately
      50%. Myocyte regeneration was evidenced by an approximately twofold increase in
      the expression of cell cycle markers (Ki67 and phosphohistone H(3)) and an
      approximately 13% reduction in mean myocyte diameter. Increased circulating
      levels of hepatocyte growth factor (HGF), leukemia inhibitory factor, and
      macrophage colony-stimulating factor were associated with the mobilization of c
      Kit-positive, CD31-positive, and CD133-positive progenitor cells and a subsequent
      increase in myocardial c-Kit-positive cells. Trophic effects of MSCs further
      activated the expression of HGF, IGF-II, and VEGF in the myocardium. The work
      highlights a cardiac repair mechanism mediated by trophic cross-talks among the
      injected MSCs, bone marrow, and heart that can be explored for noninvasive stem
      cell therapy.

PMID- 19395556
TI  - Biventricular pacing-induced acute response in baroreflex sensitivity has
      predictive value for midterm response to cardiac resynchronization therapy.
AB  - In a previous study we demonstrated that the institution of biventricular pacing
      in chronic heart failure (CHF) acutely facilitates the arterial baroreflex. The
      arterial baroreflex has important prognostic value in CHF. We hypothesized that
      the acute response in baroreflex sensitivity (BRS) after the institution of
      cardiac resynchronization therapy (CRT) has predictive value for midterm
      response. One day after implantation of a CRT device in 33 CHF patients (27
      male/6 female; age, 66.5 +/- 9.5 yr; left ventricular ejection fraction, 28 +/-
      7%) we measured noninvasive BRS and heart rate variability (HRV) in two
      conditions: CRT device switched on and switched off (on/off order randomized).
      Echocardiography was performed before implantation (baseline) and 6 mo after
      implantation (follow-up). CRT responders were defined as patients in whom left
      ventricular end-systolic volume at follow-up had decreased by > or =15%.
      Responders (69.7%) and nonresponders (30.3%) had similar baseline
      characteristics. In responders, CRT increased BRS by 30% (P = 0.03); this
      differed significantly (P = 0.02) from the average BRS change (-2%) in the
      nonresponders. CRT also increased HRV by 30% in responders (P = 0.02), but there
      was no significant difference found compared with the increase in HRV (8%) in the
      nonresponders. Receiver-operating characteristic curve analysis revealed that the
      percent BRS increase had predictive value for the discrimination of responders
      and nonresponders (area under the curve, 0.69; 95% confidence interval, 0.51
      0.87; maximal accuracy, 0.70). Our study demonstrates that a CRT-induced acute
      BRS increase has predictive value for the echocardiographic response to CRT. This
      finding suggests that the autonomic nervous system is actively involved in CRT
      related reverse remodeling.

PMID- 19395557
TI  - beta-adrenergic regulation of a novel isoform of NCX: sequence and expression of
      shark heart NCX in human kidney cells.
AB  - The function, regulation, and molecular structure of the cardiac Na(+)/Ca(2+)
      exchangers (NCXs) vary significantly among vertebrates. We previously reported
      that beta-adrenergic suppression of amphibian cardiac NCX1.1 is associated with
      specific molecular motifs. Here we investigated the bimodal, cAMP-dependent
      regulation of spiny dogfish shark (Squalus acanthias) cardiac NCX, exploring the
      effects of molecular structure, host cell environment, and ionic milieu. The
      shark cardiac NCX sequence (GenBank accession no. DQ 068478) revealed two novel
      proline/alanine-rich amino acid insertions. Wild-type and mutant shark NCXs were
      cloned and expressed in mammalian cells (HEK-293 and FlpIn-293), where their
      activities were measured as Ni(2+)-sensitive Ca(2+) fluxes (fluo 4) and membrane
      (Na(+)/Ca(2+) exchange) currents evoked by changes in extracellular Na(+)
      concentration and/or membrane potential. Regardless of Ca(2+) buffering, beta
      adrenergic stimulation of cloned wild-type shark NCX consistently produced
      bimodal regulation (defined as differential regulation of Ca(2+)-efflux and 
      influx pathways), with suppression of the Ca(2+)-influx mode and either no change
      or enhancement of the Ca(2+)-efflux mode, closely resembling results from
      parallel experiments with native shark cardiomyocytes. In contrast, mutant shark
      NCX, with deletion of the novel region 2 insertion, produced equal suppression of
      the inward and outward currents and Ca(2+) fluxes, thereby abolishing the bimodal
      nature of the regulation. Control experiments with nontransfected and dog cardiac
      NCX-expressing cells showed no cAMP regulation. We conclude that bimodal beta
      adrenergic regulation is retained in cloned shark NCX and is dependent on the
      shark's unique molecular motifs.

PMID- 19395558
TI  - Fenofibrate inhibits aldosterone-induced apoptosis in adult rat ventricular
      myocytes via stress-activated kinase-dependent mechanisms.
AB  - Aldosterone induces extracellular signal-regulated kinase (ERK)-dependent cardiac
      remodeling. Fenofibrate improves cardiac remodeling in adult rat ventricular
      myocytes (ARVM) partly via inhibition of aldosterone-induced ERK1/2
      phosphorylation and inhibition of matrix metalloproteinases. We sought to
      determine whether aldosterone caused apoptosis in cultured ARVM and whether
      fenofibrate ameliorated the apoptosis. Aldosterone (1 microM) induced apoptosis
      by increasing terminal deoxynucleotidyltransferase-mediated dUTP nick end
      labeling (TUNEL)-positive nuclei in ARVM. Spironolactone (100 nM), an aldosterone
      receptor antagonist, but not RU-486, a glucocorticoid receptor, inhibited
      aldosterone-mediated apoptosis, indicating that the mineralocorticoid receptor
      (MR) plays a role. SP-600125 (3 microM)-a selective inhibitor of c-Jun NH(2)
      terminal kinase (JNK)-inhibited aldosterone-induced apoptosis in ARVM. Although
      aldosterone increased the expression of both stress-activated protein kinases,
      pretreatment with fenofibrate (10 microM) decreased aldosterone-mediated
      apoptosis by inhibiting only JNK phosphorylation and the aldosterone-induced
      increases in Bax, p53, and cleaved caspase-3 and decreases in Bcl-2 protein
      expression in ARVM. In vivo studies demonstrated that chronic fenofibrate (100
      mg*kg body wt(-1)*day(-1)) inhibited myocardial Bax and increased Bcl-2
      expression in aldosterone-induced cardiac hypertrophy. Similarly, eplerenone, a
      selective MR inhibitor, used in chronic pressure-overload ascending aortic
      constriction inhibited myocardial Bax expression but had no effect on Bcl-2
      expression. Therefore, involvement of JNK MAPK-dependent mitochondrial death
      pathway mediates ARVM aldosterone-induced apoptosis and is inhibited by
      fenofibrate, a peroxisome proliferator-activated receptor (PPAR)alpha ligand.
      Fenofibrate mediates beneficial effects in cardiac remodeling by inhibiting
      programmed cell death and the stress-activated kinases.

PMID- 19395559
TI  - Diversity and abundance of ammonia-oxidizing archaea in hydrothermal vent
      chimneys of the juan de fuca ridge.
AB  - The abundance and diversity of archaeal ammonia monooxygenase subunit A (amoA)
      genes from hydrothermal vent chimneys at the Juan de Fuca Ridge were
      investigated. The majority of the retrieved archaeal amoA sequences exhibited
      identities of less than 95% to those in the GenBank database. Novel ammonia
      oxidizing archaea may exist in the hydrothermal vent environments.

PMID- 19395560
TI  - Species-specific cell wall binding affinity of the S-layer proteins of
      mosquitocidal bacterium Bacillus sphaericus C3-41.
AB  - The binding affinities and specificities of six truncated S-layer homology domain
      (SLH) polypeptides of mosquitocidal Bacillus sphaericus strain C3-41 with the
      purified cell wall sacculi have been assayed. The results indicated that the SLH
      polypeptide comprised of amino acids 31 to 210 was responsible for anchoring the
      S-layer subunits to the rigid cell wall layer via a distinct type of secondary
      cell wall polymer and that a motif of the recombinant SLH polypeptide comprising
      amino acids 152 to 210 (rSLH(152-210)) was essential for the stable binding of
      the S-layer with the bacterial cell walls. The quantitative assays revealed that
      the K(D) (equilibrium dissociation constant) values of rSLH(152-210) and rSLH(31
      210) with purified cell wall sacculi were 1.11 x 10(-6) M and 1.40 x 10(-6) M,
      respectively. The qualitative assays demonstrated that the SLH domain of strain
      C3-41 could bind only to the cell walls or the cells treated with 5 M guanidinium
      hydrochloride of both toxic and nontoxic B. sphaericus strains but not to those
      from other bacteria, indicating the species-specific binding of the SLH
      polypeptide of B. sphaericus with bacterial cell walls.

PMID- 19395561
TI  - Optimization of a phage amplification assay to permit accurate enumeration of
      viable Mycobacterium avium subsp. paratuberculosis cells.
AB  - A commercially available phage amplification assay, FASTPlaqueTB (Biotec
      Laboratories, Ipswich, United Kingdom), when used according to the manufacturer's
      instructions, does not permit accurate enumeration of Mycobacterium avium subsp.
      paratuberculosis. The aim of this study was to optimize the phage amplification
      assay conditions to permit accurate quantification of viable M. avium subsp.
      paratuberculosis cells. The burst time for M. avium subsp. paratuberculosis was
      initially determined to inform decisions about optimal incubation time before
      plating, and then other test parameters were altered to evaluate how the
      correlation between plaque and colony counts was affected. The D29
      mycobacteriophage replicates more slowly in M. avium subsp. paratuberculosis than
      in Mycobacterium smegmatis (used to optimize the commercial test originally), and
      the mean burst time for four M. avium subsp. paratuberulosis strains was 210 +/-
      36.8 min at 37 degrees C compared to 63 +/- 17.5 min for M. smegmatis mc(2) 155.
      To achieve 100% correlation between plaque and colony counts, the optimized phage
      assay includes the following: (i) resuspension of the samples to be tested in
      Middlebrook 7H9 broth containing 10% oleic acid-albumin-dextrose-catalase and 2
      mM calcium chloride, followed by overnight incubation at 37 degrees C before
      performance of the phage assay; (ii) a 2-h incubation of the sample with D29
      mycobacteriophage before viricide treatment; and (iii) a further 90-min
      incubation after viricide treatment and neutralization up to the burst time
      (total incubation time, 210 min) before plating with M. smegmatis mc(2) 155 in
      7H9 agar. The optimized phage amplification assay was able to detect 1 to 10
      CFU/ml of M. avium subsp. paratuberculosis in spiked milk or broth within 48 h,
      as demonstrated by the results of several blind trials.

PMID- 19395562
TI  - Robust detection and identification of multiple oomycetes and fungi in
      environmental samples by using a novel cleavable padlock probe-based ligation
      detection assay.
AB  - Simultaneous detection and identification of multiple pathogenic microorganisms
      in complex environmental samples are required in numerous diagnostic fields.
      Here, we describe the development of a novel, background-free ligation detection
      (LD) system using a single compound detector probe per target. The detector
      probes used, referred to as padlock probes (PLPs), are long oligonucleotides
      containing asymmetric target complementary regions at both their 5' and 3' ends
      which confer extremely specific target detection. Probes also incorporate a
      desthiobiotin moiety and an internal endonuclease IV cleavage site. DNA samples
      are PCR amplified, and the resulting products serve as potential targets for PLP
      ligation. Upon perfect target hybridization, the PLPs are circularized via
      enzymatic ligation, captured, and cleaved, allowing only the originally ligated
      PLPs to be visualized on a universal microarray. Unlike previous procedures, the
      probes themselves are not amplified, thereby allowing a simple PLP cleavage to
      yield a background-free assay. We designed and tested nine PLPs targeting several
      oomycetes and fungi. All of the probes specifically detected their corresponding
      targets and provided perfect discrimination against closely related nontarget
      organisms, yielding an assay sensitivity of 1 pg genomic DNA and a dynamic
      detection range of 10(4). A practical demonstration with samples collected from
      horticultural water circulation systems was performed to test the robustness of
      the newly developed multiplex assay. This novel LD system enables highly specific
      detection and identification of multiple pathogens over a wide range of target
      concentrations and should be easily adaptable to a variety of applications in
      environmental microbiology.

PMID- 19395563
TI  - Reverse transcription of 16S rRNA to monitor ribosome-synthesizing bacterial
      populations in the environment.
AB  - Identification and quantification of phylogenetically defined bacterial
      populations in the environment are often performed using molecular tools
      targeting 16S rRNA. Fluorescence in situ hybridization has been used to monitor
      the expression and processing of rRNA by targeting the 3' tail of precursor 16S
      rRNA. To expand this approach, we employed reverse transcription of total RNA
      using primer S-D-Bact-0338-a-A-18. Length heterogeneity detected by slab gel
      analysis, denaturing high-performance liquid chromatography (DHPLC) was used to
      differentiate the 5' tail of the precursor from mature 16S rRNA, and the relative
      abundance of the precursor compared to the abundance of mature 16S rRNA was shown
      to be a sensitive indicator of the physiologic state of Acinetobacter
      calcoaceticus ATCC 23055(T). Our results demonstrate that this is a sensitive and
      reliable method with a detection limit of 10 ng of single-stranded DNA. The assay
      was also used to differentiate among precursor 16S rRNA levels with mixed pure
      cultures, as well as to examine the response of a mixed activated sludge culture
      exposed to fresh growth medium and the antibiotic chloramphenicol. The results of
      this study demonstrate that this assay is a novel reverse transcription assay
      that simultaneously measures the mature and precursor 16S rRNA pools for mixed
      bacterial populations in an engineered environment. Furthermore, collection of
      the reverse transcription products derived from activated sludge samples by the
      DHPLC approach enabled identification of the active bacterial genera. Comparison
      of 16S and precursor 16S rRNA clone library results indicated that the precursor
      16S rRNA library is a more sensitive indicator for active bacteria in engineered
      environmental samples.

PMID- 19395564
TI  - In silico prediction of horizontal gene transfer events in Lactobacillus
      bulgaricus and Streptococcus thermophilus reveals protocooperation in yogurt
      manufacturing.
AB  - Lactobacillus bulgaricus and Streptococcus thermophilus, used in yogurt starter
      cultures, are well known for their stability and protocooperation during their
      coexistence in milk. In this study, we show that a close interaction between the
      two species also takes place at the genetic level. We performed an in silico
      analysis, combining gene composition and gene transfer mechanism-associated
      features, and predicted horizontally transferred genes in both L. bulgaricus and
      S. thermophilus. Putative horizontal gene transfer (HGT) events that have
      occurred between the two bacterial species include the transfer of
      exopolysaccharide (EPS) biosynthesis genes, transferred from S. thermophilus to
      L. bulgaricus, and the gene cluster cbs-cblB(cglB)-cysE for the metabolism of
      sulfur-containing amino acids, transferred from L. bulgaricus or Lactobacillus
      helveticus to S. thermophilus. The HGT event for the cbs-cblB(cglB)-cysE gene
      cluster was analyzed in detail, with respect to both evolutionary and functional
      aspects. It can be concluded that during the coexistence of both yogurt starter
      species in a milk environment, agonistic coevolution at the genetic level has
      probably been involved in the optimization of their combined growth and
      interactions.

PMID- 19395565
TI  - Archaeal diversity and the prevalence of Crenarchaeota in salt marsh sediments.
AB  - Crenarchaeal 16S rRNA sequences constituted over 70% of the archaeal clones
      recovered from three salt marsh sites dominated by different grasses. Group I.1a
      Crenarchaeota dominated at two sites, while group I.3b Crenarchaeota sequences
      were most abundant at a third site. Abundances of 16S rRNA genes related to
      "Candidatus Nitrosopumilus maritimus" differed by site and sampling date.

PMID- 19395566
TI  - Aldouronate utilization in Paenibacillus sp. strain JDR-2: Physiological and
      enzymatic evidence for coupling of extracellular depolymerization and
      intracellular metabolism.
AB  - Paenibacillus sp. strain JDR-2, an aggressively xylanolytic bacterium isolated
      from decaying sweet gum wood, secretes a multimodular glycohydrolase family GH10
      endoxylanase (XynA1) anchored to the cell surface. The gene encoding XynA1 is
      part of a xylan utilization regulon that includes an aldouronate utilization gene
      cluster with genes encoding a GH67 alpha-glucuronidase (AguA), a GH10
      endoxylanase (XynA2), and a GH43 arabinofuranosidase/beta-xylosidase (XynB). Here
      we show that this Paenibacillus sp. strain is able to utilize
      methylglucuronoxylose (MeGAX(1)), an aldobiuronate product that accumulates
      during acid pretreatment of lignocellulosic biomass, and
      methylglucuronoxylotriose (MeGAX(3)), the product of the extracellular XynA1
      acting on methylglucuronoxylan (MeGAX(n)). The average rates of utilization of
      MeGAX(n), MeGAX(1), and MeGAX(3) were 149.8, 59.4, and 54.3 microg xylose
      equivalents.ml(-1).h(-1), respectively, and were proportional to the specific
      growth rates on the substrates. AguA was active with MeGAX(1) and MeGAX(3),
      releasing 4-O-methyl-d-glucuronate alpha-1,2 linked to a nonreducing terminal
      xylose residue. XynA2 converted xylotriose, generated by the action of AguA on
      MeGAX(3), to xylose and xylobiose. The ability to utilize MeGAX(1) provides a
      novel metabolic potential for bioconversion of acid hydrolysates of
      lignocellulosics. The 2.8-fold-greater rate of utilization of polymeric MeGAX(n)
      than that of MeGAX(3) indicates that there is coupling of extracellular
      depolymerization, assimilation, and intracellular metabolism, allowing
      utilization of lignocellulosics with minimal pretreatment. Along with adjacent
      genes encoding transcriptional regulators and ABC transporter proteins, the aguA
      and xynA2 genes in the cluster described above contribute to the efficient
      utilization of aldouronates derived from dilute acid and/or enzyme pretreatment
      protocols applied to the conversion of hemicellulose to biofuels and chemicals.

PMID- 19395567
TI  - Assessment of the diversity, abundance, and ecological distribution of members of
      candidate division SR1 reveals a high level of phylogenetic diversity but limited
      morphotypic diversity.
AB  - We used a combination of 16S rRNA gene clone library surveys, quantitative PCR
      (qPCR) analysis, and fluorescent in situ hybridization to investigate the
      diversity, abundance, and distribution of members of candidate division SR1 in
      multiple habitats. Using SR1-specific 16S rRNA gene primers, we identified
      multiple novel SR1 lineages in four different anaerobic environments: sediments
      from Zodletone Spring, a sulfide- and sulfur-rich spring in southwestern
      Oklahoma; inner layers of microbial mats obtained from Sperm Pool, a high
      temperature, low-pH pool (55 degrees C, pH 2.5) in Yellowstone National Park;
      fresh bovine ruminal contents; and anaerobic freshwater pond sediments (Duck
      Pond) in Norman, Oklahoma. qPCR analysis indicated that SR1 members constitute a
      small fraction (<0.01%) of the microbial communities in Duck Pond and ruminal
      samples but constitute a significant fraction (11.6 and 48.7%) of the total
      number of bacterial 16S rRNA genes in Zodletone Spring and the inner layers of
      Sperm Pool microbial mat samples, respectively. By using SR1-specific fluorescent
      probes, filamentous cells were identified as the sole SR1 morphotype in all
      environments examined, with the exception of Sperm Pool, where a second bacillus
      morphotype was also identified. Using a full-cycle 16S rRNA approach, we show
      that each of these two morphotypes corresponds to a specific phylogenetic lineage
      identified in the Sperm Pool clone library. This work greatly expands the
      intralineage phylogenetic diversity within candidate division SR1 and provides
      valuable quantification and visualization tools that could be used for
      investigating the ecological roles, dynamics, and genomics of this as-yet
      uncultured bacterial phylum.

PMID- 19395568
TI  - Widespread abundance of functional bacterial amyloid in mycolata and other gram
      positive bacteria.
AB  - Until recently, extracellular functional bacterial amyloid (FuBA) has been
      detected and characterized in only a few bacterial species, including Escherichia
      coli, Salmonella, and the gram-positive organism Streptomyces coelicolor. Here we
      probed gram-positive bacteria with conformationally specific antibodies and
      revealed the existence of FuBA in 12 of 14 examined mycolata species, as well as
      six other distantly related species examined belonging to the phyla
      Actinobacteria and Firmicutes. Most of the bacteria produced extracellular
      fimbriae, sometimes copious amounts of them, and in two cases large extracellular
      fibrils were also produced. In three cases, FuBA was revealed only after
      extensive removal of extracellular material by saponification, indicating that
      there is integrated attachment within the cellular envelope. Spores of species in
      the genera Streptomyces, Bacillus, and Nocardia were all coated with amyloids.
      FuBA was purified from Gordonia amarae (from the cell envelope) and
      Geodermatophilus obscurus, and they had the morphology, tinctorial properties,
      and beta-rich structure typical of amyloid. The presence of approximately 9-nm
      wide amyloids in the cell envelope of G. amarae was visualized by transmission
      electron microscopy analysis. We conclude that amyloid is widespread among gram
      positive bacteria and may in many species constitute a hitherto overlooked
      integral part of the spore and the cellular envelope.

PMID- 19395569
TI  - Utilization of mucus from the coral Acropora palmata by the pathogen Serratia
      marcescens and by environmental and coral commensal bacteria.
AB  - In recent years, diseases of corals caused by opportunistic pathogens have become
      widespread. How opportunistic pathogens establish on coral surfaces, interact
      with native microbiota, and cause disease is not yet clear. This study compared
      the utilization of coral mucus by coral-associated commensal bacteria
      ("Photobacterium mandapamensis" and Halomonas meridiana) and by opportunistic
      Serratia marcescens pathogens. S. marcescens PDL100 (a pathogen associated with
      white pox disease of Acroporid corals) grew to higher population densities on
      components of mucus from the host coral. In an in vitro coculture on mucus from
      Acropora palmata, S. marcescens PDL100 isolates outgrew coral isolates. The white
      pox pathogen did not differ from other bacteria in growth on mucus from a nonhost
      coral, Montastraea faveolata. The ability of S. marcescens to cause disease in
      acroporid corals may be due, at least in part, to the ability of strain PDL100 to
      build to higher population numbers within the mucus surface layer of its
      acroporid host. During growth on mucus from A. palmata, similar glycosidase
      activities were present in coral commensal bacteria, in S. marcescens PDL100, and
      in environmental and human isolates of S. marcescens. The temporal regulation of
      these activities during growth on mucus, however, was distinct in the isolates.
      During early stages of growth on mucus, enzymatic activities in S. marcescens
      PDL100 were most similar to those in coral commensals. After overnight incubation
      on mucus, enzymatic activities in a white pox pathogen were most similar to those
      in pathogenic Serratia strains isolated from human mucosal surfaces.

PMID- 19395570
TI  - Toward cloning of the magnetotactic metagenome: identification of magnetosome
      island gene clusters in uncultivated magnetotactic bacteria from different
      aquatic sediments.
AB  - In this report, we describe the selective cloning of large DNA fragments from
      magnetotactic metagenomes from various aquatic habitats. This was achieved by a
      two-step magnetic enrichment which allowed the mass collection of environmental
      magnetotactic bacteria (MTB) virtually free of nonmagnetic contaminants. Four
      fosmid libraries were constructed and screened by end sequencing and
      hybridization analysis using heterologous magnetosome gene probes. A total of 14
      fosmids were fully sequenced. We identified and characterized two fosmids, most
      likely originating from two different alphaproteobacterial strains of MTB that
      contain several putative operons with homology to the magnetosome island (MAI) of
      cultivated MTB. This is the first evidence that uncultivated MTB exhibit similar
      yet differing organizations of the MAI, which may account for the diversity in
      biomineralization and magnetotaxis observed in MTB from various environments.

PMID- 19395571
TI  - Characterization of tetracycline-resistant Streptococcus thermophilus isolates
      from Italian soft cheeses.
AB  - Tetracycline-resistant Streptococcus thermophilus isolates from soft cheeses
      harbored the genes tet(S), tet(M), and tet(L). Molecular analysis of these genes
      revealed their expression, localization on plasmids or Tn916-Tn1545 family
      transposons, and their similarity with published sequences. The study highlights
      the importance of an accurate safety assessment of using S. thermophilus as a
      starter culture.

PMID- 19395572
TI  - Requirement of polyphosphate by Pseudomonas fluorescens Pf0-1 for competitive
      fitness and heat tolerance in laboratory media and sterile soil.
AB  - Knowledge of the genetic basis for bacterial survival and persistence in soil is
      a critical component in the development of successful biological control
      strategies and for understanding the ecological success of bacteria. We found a
      locus specifying polyphosphate kinase (ppk) and a nonpredicted antisense RNA
      (iiv8) in Pseudomonas fluorescens Pf0-1 to be necessary for optimal competitive
      fitness in LB broth culture and sterile loam soil. Pf0-1 lacking ppk and iiv8 was
      more than 10-fold less competitive against wild-type Pf0-1 in sterile loam soil
      low in inorganic phosphate. Studies indicated that ppk, and not iiv8, was
      required for competitive fitness. No role for iiv8 was identified. While a ppk
      and iiv8 mutant of Pf0-1 did not have increased sensitivity to osmotic,
      oxidative, and acid stress, it was more sensitive to elevated temperatures in
      laboratory medium and during growth in sterile soil. ppk was shown to be part of
      the Pho regulon in P. fluorescens, being upregulated in response to a low
      external P(i) concentration. Of importance, overproduction of polyphosphate in
      the soil environment appears to be more deleterious than production of none at
      all. Our findings reveal a new role for polyphosphate (and the need for proper
      regulation of its production) in competitive fitness of P. fluorescens in
      laboratory and soil environments.

PMID- 19395573
TI  - Identification of promoters for efficient gene expression in Magnetospirillum
      gryphiswaldense.
AB  - To develop an expression system for the magnetotactic bacterium Magnetospirillum
      gryphiswaldense, we compared gene expression from the widely used Escherichia
      coli P(lac) promoter with that from known and predicted genuine M.
      gryphiswaldense promoters. With the use of green fluorescent protein as a
      reporter, the highest expression level was observed with the magnetosomal
      P(mamDC) promoter. We demonstrate that this promoter can be used for the
      expression of modified magnetosome proteins to generate "antibody-binding"
      magnetosomes.

PMID- 19395574
TI  - Characterization of the Tn916 conjugative transposon in a food-borne strain of
      Lactobacillus paracasei.
AB  - Food-borne antibiotic-resistant lactic acid bacteria have received growing
      attention in the past few years. We have recently identified tetracycline
      resistant Lactobacillus paracasei in samples of milk and natural whey starter
      cultures employed in the manufacturing process of a typical Italian fermented
      dairy product, Mozzarella di Bufala Campana. In the present study, we have
      characterized at the molecular level the genetic context of tetracycline
      resistance determinants in these natural strains, which we have identified as
      tet(M). This gene was present in 21 independent isolates, whose fingerprinting
      profiles were distributed into eight different repetitive extragenic palindromic
      groups by cluster analysis. We provide evidence that the gene is associated with
      the broad-host, conjugative transposon Tn916, which had never before been
      described to occur in L. paracasei. PCR analysis of four independent isolates by
      use of specifically designed primer pairs detected the presence of a circular
      intermediate form of the transposon, carrying a coupling sequence (GGCAAA)
      located between the two termini of Tn916. This novel coupling sequence conferred
      low conjugation frequency in mating experiments with the recipient strain JH2-2
      of Enterococcus faecalis.

PMID- 19395575
TI  - Phenotypic and transcriptomic analyses of mildly and severely salt-stressed
      Bacillus cereus ATCC 14579 cells.
AB  - Bacteria are able to cope with the challenges of a sudden increase in salinity by
      activating adaptation mechanisms. In this study, exponentially growing cells of
      the pathogen Bacillus cereus ATCC 14579 were exposed to both mild (2.5% [wt/vol]
      NaCl) and severe (5% [wt/vol] NaCl) salt stress conditions. B. cereus continued
      to grow at a slightly reduced growth rate when it was shifted to mild salt stress
      conditions. Exposure to severe salt stress resulted in a lag period, and after 60
      min growth had resumed, with cells displaying a filamentous morphology. Whole
      genome expression analyses of cells exposed to 2.5% salt stress revealed that the
      expression of these cells overlapped with the expression of cells exposed to 5%
      salt stress, suggesting that the corresponding genes were involved in a general
      salt stress response. Upregulation of osmoprotectant, Na(+)/H(+), and di- and
      tripeptide transporters and activation of an oxidative stress response were
      noticeable aspects of the general salt stress transcriptome response. Activation
      of this response may confer cross-protection against other stresses, and indeed,
      increased resistance to heat and hydrogen peroxide could be demonstrated after
      preexposure to salt. A temporal shift between the transcriptome response and
      several phenotypic responses of severely salt-stressed cells was observed. After
      resumption of growth, these cells showed cellular filamentation, reduced
      chemotaxis, increased catalase activity, and optimal oxidative stress resistance,
      which corresponded to the transcriptome response displayed in the initial lag
      period. The linkage of transcriptomes and phenotypic characteristics can
      contribute to a better understanding of cellular stress adaptation strategies and
      possible cross-protection mechanisms.

PMID- 19395576
TI  - Inactivation of enteric viruses in minimally processed berries and herbs.
AB  - Several hepatitis A virus (HAV) and human norovirus (HuNoV) outbreaks due to
      consumption of contaminated berries and vegetables have recently been reported.
      Model experiments were performed to determine the effectiveness of freeze-drying,
      freeze-drying combined with heating, and steam blanching for inactivation of
      enteric viruses that might be present on the surface of berries and herbs.
      Inactivation of HAV and inactivation of feline calicivirus, a surrogate for
      HuNoV, were assessed by viral culturing and quantitative reverse transcription
      PCR (RT-PCR), whereas HuNoV survival was determined only by quantitative RT-PCR.
      While freeze-drying barely reduced (<1.3 log(10) units) the amount of HAV RNA
      detected in frozen produce, a greater decline in HAV infectivity was observed.
      The resistance of HuNoV genogroup I (GI) to freeze-drying was significantly
      higher than that of HuNoV GII on berries. Addition of a terminal dry heat
      treatment at 120 degrees C after freeze-drying enhanced virus inactivation by at
      least 2 log(10) units, except for HuNoV GII. The results suggest that steam
      blanching at 95 degrees C for 2.5 min effectively inactivated infectious enteric
      viruses if they were present in herbs. Our results provide data for adjusting
      food processing technologies if viral contamination of raw materials is
      suspected.

PMID- 19395577
TI  - The neuroprotective effect of methanol extract of gagamjungjihwan and fructus
      euodiae on ischemia-induced neuronal and cognitive impairment in the rat.
AB  - Gagamjungjihwan (GJ), a decoction consisting of five herbs including ginseng,
      Acori Graminei Rhizoma, Uncariae Ramulus et Uncus, Polygalae Radic and Frustus
      Euodiae (FE), has been widely used as herbal treatment for ischemia. In order to
      investigate the neuroprotective action of this novel prescription, we examined
      the influence of GJ and FE on learning and memory using the Morris water maze and
      studied their affects on the central cholinergic system in the hippocampus with
      neuronal and cognitive impairment. After middle cerebral artery occlusion was
      applied for 2 h, rats were administered GJ (200 mg kg(-1), p.o.) or FE (200 mg
      kg(-1), p.o.) daily for 2 weeks, followed by training and performance of the
      Morris water maze tasks. Rats with ischemic insults showed impaired learning and
      memory of the tasks. Pre-treatment with GJ and FE produced improvement in the
      escape latency to find the platform. Pre-treatments with GJ and FE also reduced
      the loss of cholinergic immunoreactivity in the hippocampus. The results
      demonstrated that GJ and FE have a protective effect against ischemia-induced
      neuronal and cognitive impairment. Our results suggest that GJ and FE might be
      useful in the treatment of vascular dementia.

PMID- 19395578
TI  - Changes in chest roentgenogram of sarcoidosis patients during a clinical trial of
      infliximab therapy: comparison of different methods of evaluation.
AB  - BACKGROUND: The best method to interpret the chest roentgenogram and its
      sensitivity to detect effect of treatment for sarcoidosis remains unclear. In a
      double-blind, randomized trial of infliximab for chronic pulmonary sarcoidosis,
      changes in serial chest roentgenograms were examined by radiologists, blinded to
      order or treatment. METHODS: Chest roentgenograms were obtained at 0, 6, and 24
      weeks of therapy with either placebo, 3 mg/kg infliximab, or 5 mg/kg infliximab.
      Films were reviewed in random order by two independent radiologists, unaware of
      treatment. The films were compared using two methods: the prespecified objective
      assessment, a scoring system previously proposed by Muers; and the post hoc
      assessment, a 5-point Likert scale global assessment between two films. RESULTS:
      Of 138 patients enrolled in the study, chest roentgenograms for all studies were
      available on 130 patients. There was only fair agreement between the two
      radiologists in the original stage of the chest roentgenogram (weighted kappa =
      0.43; 95% confidence interval [CI], 0.32 to 0.54). For the Likert scale of global
      assessment of change, there was good agreement between the two readers (weighted
      kappa = 0.61; 95% CI, 0.51 to 0.71). There was good correlation between the two
      readers for the various components of the Muers score, especially the
      reticulonodular (R) score (R = 0.578; p < 0.05). The initial R score was
      positively correlated with improvement in FVC with infliximab therapy (R = 0.239;
      p < 0.05). CONCLUSION: Global assessment and the Muers scoring system were
      associated with good agreement between two expert readers. Improvement in both
      scores correlated with improvement in FVC. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT00073437.

PMID- 19395579
TI  - Heart rate recovery after 6-min walk test predicts survival in patients with
      idiopathic pulmonary fibrosis.
AB  - BACKGROUND: In patients with idiopathic pulmonary fibrosis (IPF), our objectives
      were to identify predictors of abnormal heart rate recovery (HRR) at 1 min after
      completion of a 6-min walk test (6MWT) [HRR1] and 2 min after completion of a
      6MWT (HRR2), and to determine whether abnormal HRR predicts mortality. METHODS:
      From 2003 to 2008, we identified IPF patients who had been evaluated at our
      center (n = 76) with a pulmonary physiologic examination and the 6MWT. We used
      logistic regression to identify predictors of abnormal HRR, the product-limit
      method to compare survival in the sample stratified on HRR, and Cox proportional
      hazards analysis to estimate the prognostic capability of abnormal HRR. RESULTS:
      Cutoff values were 13 beats for abnormal HRR1 and 22 beats for HRR2. In a
      multivariable model, predictors of abnormal HRR1 were diffusing capacity of the
      lung for carbon monoxide (odds ratio [OR], 0.4 per 10% predicted; 95% confidence
      interval [CI], 0.2 to 0.7; p = 0.003), change in heart rate from baseline to
      maximum (OR, 0.9; 95% CI, 0.8 to 0.97; p = 0.01), and having a right ventricular
      systolic pressure > 35 mm Hg as determined by transthoracic echocardiogram (OR,
      12.7; 95% CI, 2.0 to 79.7; p = 0.01). Subjects with an abnormal HRR had
      significantly worse survival than subjects with a normal HRR (for HRR1, p =
      0.0007 [log-rank test]; for HRR2, p = 0.03 [log-rank test]); these results held
      for the subgroup of 30 subjects without resting pulmonary hypertension (HRR1, p =
      0.04 [log-rank test]). Among several candidate variables, abnormal HRR1 appeared
      to be the most potent predictor of mortality (hazard ratio, 5.2; 95% CI, 1.8 to
      15.2; p = 0.004). CONCLUSION: Abnormal HRR after 6MWT predicts mortality in IPF
      patients. Research is needed to confirm these findings prospectively and to
      examine the mechanisms of HRR in IPF patients.

PMID- 19395580
TI  - Predictors of short-term rehospitalization following discharge of patients
      hospitalized with community-acquired pneumonia.
AB  - BACKGROUND: Among patients hospitalized for community-acquired pneumonia (CAP),
      the risk factors for short-term hospital readmission after discharge are unknown.
      METHODS: We conducted a prospective observational study of 1,117 patients who had
      been discharged alive after hospitalization for CAP. We collected variables
      associated with CAP severity at hospital admission, in-hospital clinical
      evolution, clinical instability factors on hospital discharge, therapy employed
      during hospitalization, and diagnostic bacteriology. We assessed hospital
      readmission within 30 days after discharge for the index hospitalization. Risk
      factors independently associated with 30-day hospital readmission were identified
      using Cox regression models. RESULTS: Of the 81 patients (7.3%) who were
      readmitted to the hospital within 30 days, 29 (35.8%) were rehospitalized for
      pneumonia-related causes. Variables associated with pneumonia-related hospital
      readmission were treatment failure (hazard ratio [HR], 2.9; 95% CI, 1.2 to 6.8),
      and one or more instability factors on hospital discharge (HR, 2.8; 95% CI, 1.3
      to 6.2). The predictive performance of these variables measured by the area under
      the curve (AUC) of the receiver operating characteristic was 0.65. Variables
      associated with pneumonia-unrelated hospital readmission were age >or= 65 years
      (HR, 4.5; 95% CI, 1.4 to 14.7), Charlson comorbidity index >or= 2 (HR, 1.9; 95%
      CI, 1.0 to 3.4), and decompensated comorbidities during in-hospital evolution
      (HR, 3.5; 95% CI, 2.0 to 6.3); the AUC for this model was 0.77. Patients with at
      least two risk factors were at significantly increased risk of 30-day hospital
      readmission (pneumonia-related CAP: HR, 9.0; 95% CI, 3.2 to 25.3; pneumonia
      unrelated CAP: HR, 5.3; 95% CI, 1.6 to 18.1). CONCLUSIONS: Among patients
      hospitalized for CAP, different risk factors are associated with hospital
      readmission related to pneumonia or to other causes. The identification of two
      different groups of patients who were at high risk of hospital readmission raises
      the possibility that different management strategies could decrease the rate of
      hospital readmissions.

PMID- 19395581
TI  - Effect of age on relationship between exhaled nitric oxide and airway
      hyperresponsiveness in asthmatic children.
AB  - BACKGROUND: Numerous studies have examined the relationship between the
      fractional concentration of exhaled nitric oxide (Feno) and airway
      hyperresponsiveness (AHR). Our objective was to determine the effects of age on
      the relationship between Feno and AHR in asthmatic children. METHODS: AHR was
      examined in 267 asthmatic patients (age range, 5 to 20 years). A challenge test
      was performed using acetylcholine chloride (Ach). We determined the provocative
      concentration of Ach producing a 20% decrease in FEV(1) from baseline (PC(20)).
      Feno was examined using the recommended online method before the Ach challenge
      test. RESULTS: In children < 12 years of age (range, 5 to 11 years), decreasing
      AHR (PC(20)) was significantly related to higher Feno (r = -0.43; beta = -0.28; p
      < 0.001). In adolescents >or= 12 years of age (range, 12 to 20 years), decreasing
      PC(20) was associated with peripheral airway obstruction (FEV(1): r = 0.32; beta
      = 5.5; p = 0.002; forced expiratory flow at 50% of the FVC: r = 0.24; beta=8.4; p
      = 0.006; and forced expiratory flow at 25% of FVC: r = 0.28; beta=11.4; p =
      0.002). AHR and Feno were weakly related (r = -0.18; beta = -0.14; p = 0.02).
      CONCLUSIONS: In children with asthma, AHR is associated with airway inflammation.
      AHR in children with asthma may consist of variable components mainly reflecting
      airway inflammation. In contrast, in adolescents with asthma, AHR is associated
      with airway structural changes and weakly with airway inflammation. AHR in
      adolescents with asthma may consist of chronic components mainly reflecting
      airway remodeling.

PMID- 19395582
TI  - Incidence of pleural effusions in idiopathic and familial pulmonary arterial
      hypertension patients.
AB  - BACKGROUND: Pleural effusion occurs often in patients with left heart failure.
      There are no large-scale clinical studies investigating the incidence of pleural
      effusion in patients with right heart failure (RHF) alone. OBJECTIVES: To
      determine the incidence of pleural effusions in patients with idiopathic
      pulmonary arterial hypertension (IPAH) and familial pulmonary arterial
      hypertension (FPAH). METHODS: Consecutive IPAH and FPAH patients who were treated
      at Vanderbilt University Medical Center were retrospectively studied. Pleural
      effusions were detected by chest radiograph, chest CT scan, ultrasound, or
      autopsy. RESULTS: Thirty-one of 147 patients (21.1%) with IPAH (128 patients) or
      FPAH (19 patients) had pleural effusions. Ten patients had explanations for the
      pleural effusions other than RHF. Two patients had no obvious explanations. The
      remaining 19 patients had RHF. When compared with the patients without pleural
      effusions, the patients with pleural effusions due to RHF had significantly
      higher mean right atrial pressure (16.0 +/- 6.8 vs 8.8 +/- 5.5 mm Hg,
      respectively; p < 0.001). There was no significant difference in other
      hemodynamic parameters between the two patient groups. The majority of effusions
      due to RHF are trace to small (63.2%) and right sided (57.9%) or bilateral
      (26.3%). Of the 19 patients with pleural effusions due to RHF, 8 patients had
      ascites, and 1 patient had moderate pericardial effusion. Four of the five
      patients who underwent thoracentesis had transudates. CONCLUSIONS: Our study in
      IPAH and FPAH patients demonstrates that pleural effusions frequently occur in
      patients with isolated RHF.

PMID- 19395583
TI  - Dichloroacetate modulates the oxidative stress and inflammatory response to
      exercise in COPD.
AB  - BACKGROUND: Impaired skeletal muscle function contributes to exercise intolerance
      in patients with COPD. Exercise-induced oxidative stress may initiate or
      accelerate impaired muscle function. Dichloroacetate (DCA) activates muscle
      pyruvate dehydrogenase complex (PDC) at rest, reducing inertia in mitochondrial
      energy delivery at the onset of exercise and thereby diminishing anaerobic energy
      production. This study aimed to determine whether DCA infusion also may reduce
      exercise-induced systemic oxidative stress and inflammatory response in patients
      with COPD. METHODS: A randomized, double-blind crossover design was used in which
      13 patients with COPD performed maximal cycle exercise after an IV infusion of
      DCA (50 mg/kg body mass) or saline solution (placebo). Venous blood was sampled
      before exercise, and immediately, 30 min, and 2 h after exercise. Urine samples
      were obtained before and 2 h after exercise. RESULTS: Peak workload improved
      significantly after DCA infusion compared to placebo (10%; p < 0.01). Urinary
      uric acid levels after exercise were significantly lower in the DCA condition
      than in the placebo condition, whereas no significant difference was observed for
      urinary malondialdehyde levels. Oxidized glutathione (GSSG) levels were
      significantly increased 2 h after exercise in the placebo condition (p < 0.02)
      but not after DCA infusion. No changes in reduced glutathione (GSH), GSSG/GSH
      ratio, and superoxide dismutase activity were observed. Plasma interleukin (IL)-6
      levels significantly increased 2 h after exercise only in the DCA condition (p <
      0.01). CONCLUSIONS: This study shows that improved performance after a
      pharmacologic intervention known to activate PDC was accompanied by an enhanced
      IL-6 response and a limited reduction in exercise-induced systemic oxidative
      stress.

PMID- 19395584
TI  - Pharmacodynamics of a novel designer natriuretic peptide, CD-NP, in a first-in
      human clinical trial in healthy subjects.
AB  - CD-NP is a novel chimeric natriuretic peptide (NP) consisting of the 22-amino
      acid (AA) human C-type natriuretic peptide (CNP), a venodilating peptide with
      limited renal actions and minimal effects on blood pressure, and the 15-AA C
      terminus of Dendroaspis NP (DNP). The rationale for the design of CD-NP was to
      enhance the renal actions of CNP, the ligand for natriuretic peptide receptor-B,
      but without inducing excessive hypotension. Here we report the first-in-human
      studies for CD-NP, which represent the first successful clinical testing of a
      chimeric NP demonstrating in normal human volunteers that CD-NP possesses cyclic
      guanosine monophosphate-activating, natriuretic, and aldosterone-suppressing
      properties without inducing excessive hypotension, laying the foundation for
      additional studies on this first-in-class new cardiovascular therapeutic in human
      heart failure, which are now underway worldwide.

PMID- 19395586
TI  - Population pharmacokinetics of telbivudine and determination of dose adjustment
      for patients with renal impairment.
AB  - Telbivudine is a new nucleoside analog indicated for the treatment of chronic
      hepatitis B infection. A population pharmacokinetic model was developed based on
      data pooled from 16 early phase studies in 363 healthy participants and patients.
      Telbivudine was administered as single and/or multiple doses of 25 to 1800 mg
      daily for up to 28 days. A 2-compartment model with first-order input and lag
      time provided the best fit to the data. A final model was built with identified
      covariates, including creatinine clearance on plasma clearance, dose and race on
      bioavailability fraction, and body weight on central volume of distribution. The
      final model was applied to simulate steady-state exposure for patients with
      impaired renal function for various dosing regimens. Results from these
      simulation analyses support that in patients with moderate to severe renal
      impairment or end-stage renal disease, reduced daily doses of telbivudine could
      be an alternative to interval adjustment to achieve exposure comparable to
      patients with normal renal function or mild renal impairment treated with the
      full clinical dose.

PMID- 19395585
TI  - Phase I study of the effect of gastric acid pH modulators on the bioavailability
      of oral dasatinib in healthy subjects.
AB  - Dasatinib is a tyrosine kinase inhibitor (including BCR-ABL and the SRC family)
      that is effective in patients with chronic myeloid leukemia. Dasatinib has pH
      dependent solubility and is bioavailable as an oral formulation. The effect of
      gastric pH modifiers on dasatinib pharmacokinetics is evaluated in an open-label,
      randomized, 3-period, 3-treatment crossover study. Twenty-four healthy subjects
      receive treatment A (2 doses of dasatinib 50 mg separated by 12 hours), treatment
      B (famotidine 40 mg given 2 hours after dasatinib 50 mg and 10 hours before
      another dose of dasatinib 50 mg), and treatment C (30 mL of an antacid containing
      aluminum/magnesium hydroxides given 2 hours before dasatinib 50 mg and
      concomitantly with dasatinib 50 mg 12 hours after the previous dasatinib dose); a
      7-day washout separates each treatment period. When famotidine is administered 2
      hours after dasatinib, dasatinib exposure is similar to dasatinib administered
      alone. However, dasatinib exposure is reduced by approximately 60% when
      famotidine is administered 10 hours before dasatinib dosing. In contrast,
      dasatinib exposure is unchanged when antacid (Maalox) is administered 2 hours
      before dasatinib; but when the antacid is coadministered with dasatinib,
      dasatinib exposure is reduced by approximately 55% to 58%. This indicates that
      H(2)-receptor antagonists should not be coadministered with dasatinib. Dasatinib
      may be administered with acid-neutralizing antacids if the doses are temporally
      separated by at least 2 hours.

PMID- 19395587
TI  - Rye Bs disclose ancestral sequences in cereal genomes with a potential role in
      gametophyte chromatid segregation.
AB  - Two sequence families, E3900 and D1100, are amplified on the subtelomeric domain
      of the long arm of rye B chromosomes, the region that controls its drive
      mechanism. In this work, polymerase chain reaction (PCR) with a number of primers
      spanning E3900 shows that the organization and nucleotide sequence of E3900
      related portions are present and highly conserved on rye A chromosomes as well as
      in other cereals. Quantitative Real-Time PCR estimates two E3900 sequences to be
      represented in 100-150 copies on Bs and at least as single copies on As. A novel
      E3900-related sequence, with a deletion that results in a frameshift and
      subsequently an open reading frame with putative DNA binding motifs, is
      identified. Expression analysis of E3900 indicates identical transcription levels
      in leaves from plants with and without Bs, showing that the expression of these
      sequences must be silenced on Bs and tightly regulated on As in leaves. In
      contrast, E3900 transcription is upregulated during meiosis exclusively in plants
      with Bs, maintaining a high level of transcription in the gametophyte.
      Interestingly, Bs not only influence their own chromatid segregation but also
      that of the regular chromosome complement of both rye and wheat. There is a
      drastic increase in frequency of disrupted metaphase and anaphase cells in the
      first mitosis of pollen grains carrying Bs, which appears to be due to anomalous
      adherences between sister chromatids. Taken together, this work provides insight
      into how E3900 sequences are potentially associated with important evolutionary
      mechanisms involved in basic cellular processes.

PMID- 19395588
TI  - Sixty million years in evolution of soft grain trait in grasses: emergence of the
      softness locus in the common ancestor of Pooideae and Ehrhartoideae, after their
      divergence from Panicoideae.
AB  - Together maize, Sorghum, rice, and wheat grass (Poaceae) species are the most
      important cereal crops in the world and exhibit different "grain endosperm
      texture." This trait has been studied extensively in wheat because of its pivotal
      role in determining quality of products obtained from wheat grain. Grain softness
      protein-1 and Puroindolines A and B (grain storage proteins), encoded by Ha-like
      genes: Gsp-1, Pina, and Pinb, of the Hardness (Ha) locus, are the main
      determinants of the grain softness/hardness trait in wheat. The origin and
      evolution of grain endosperm texture in grasses was addressed by comparing
      genomic sequences of the Ha orthologous region of wheat, Brachypodium, rice, and
      Sorghum. Results show that the Ha-like genes are present in wheat and
      Brachypodium but are absent from Sorghum bicolor. A truncated remnant of an Ha
      like gene is present in rice. Synteny analysis of the genomes of these grass
      species shows that only one of the paralogous Ha regions, created 70 My by whole
      genome duplication, contained Ha-like genes. The comparative genome analysis and
      evolutionary comparison with genes encoding grain reserve proteins of grasses
      suggest that an ancestral Ha-like gene emerged, as a new member of the prolamin
      gene family, in a common ancestor of the Pooideae (Triticeae and Brachypoidieae
      tribes) and Ehrhartoideae (rice), between 60 and 50 My, after their divergence
      from Panicoideae (Sorghum). It was subsequently lost in Ehrhartoideae. Recurring
      duplications, deletions, and/or truncations occurred independently and appear to
      characterize Ha-like gene evolution in the grass species. The Ha-like genes
      gained a new function in Triticeae, such as wheat, underlying the soft grain
      phenotype. Loss of these genes in some wheat species leads, in turn, to hard
      endosperm seeds.

PMID- 19395589
TI  - Fenofibrate-induced muscular toxicity is associated with a metabolic shift
      limited to type-1 muscles in rats.
AB  - Morphological changes and mRNA expression levels in type-1 predominant soleus and
      type-2 predominant tensor fasciae latae muscles of rats treated with fenofibrate
      were investigated. After fenofibrate by oral gavage at 300 mg/kg/day for 28 days,
      degeneration/necrosis and regeneration of muscle fibers, cellular infiltration,
      and fibrosis were seen in soleus muscle. Additionally, expression of PDK4, CPT1
      M, CPT2, and FACO mRNAs was increased. In contrast, no morphological changes or
      mRNA induction were apparent in tensor fasciae latae muscle. These data suggest
      that sensitivity to fenofibrate-induced muscle toxicity differs among muscles,
      with only type-1 fibers being susceptible. The up-regulation of PDK4, CPTs and
      FACO mRNA expression in soleus muscle indicates that the energy source is
      switched from glucose to fatty acids, and this might be related to the observed
      fenofibrate-induced muscular toxicity.

PMID- 19395590
TI  - Gene expression studies reveal that DNA damage, vascular perturbation, and
      inflammation contribute to the pathogenesis of carbonyl sulfide neurotoxicity.
AB  - Carbonyl sulfide (COS) is an odorless gas that produces highly reproducible
      lesions in the central nervous system. In the present study, the time course for
      the development of the neurotoxicological lesions was defined and the gene
      expression changes occurring in the posterior colliculus upon exposure to COS
      were characterized. Fischer 344 rats were exposed to 0 or 500 ppm COS for one,
      two, three, four, five, eight, or ten days, six hours per day. On days 1 and 2,
      no morphological changes were detected; on day 3, 10/10 (100%) rats had necrosis
      in the posterior colliculi; and on day 4 and later, necrosis was observed in
      numerous areas of the brain. Important gene expression changes occurring in the
      posterior colliculi after one or two days of COS exposure that were predictive of
      the subsequent morphological findings included up-regulation of genes associated
      with DNA damage and G1/S checkpoint regulation (KLF4, BTG2, GADD45g), apoptosis
      (TGM2, GADD45g, RIPK3), and vascular mediators (ADAMTS, CTGF, CYR61, VEGFC).
      Proinflammatory mediators (CCL2, CEBPD) were up-regulated prior to increases in
      expression of the astrocytic marker GFAP and macrophage marker CSF2rb1. These
      gene expression findings were predictive of later CNS lesions caused by COS
      exposure and serve as a model for future investigations into the mechanisms of
      disease in the central nervous system.

PMID- 19395591
TI  - Neutralization of IL-10 exacerbates cycloheximide-induced hepatocellular
      apoptosis and necrosis.
AB  - Cycloheximide (CHX)-induced liver injury in rats has been characterized by
      hepatocellular apoptosis and necrosis. We previously reported that Kupffer cell
      inactivation causes a reduction of IL-10 production, resulting in the
      exacerbation of CHX-induced liver injury. In this study, we directly evaluate the
      role of IL-10 in liver injury by a pretreatment with anti-IL-10 neutralizing
      antibody (IL-10Ab). Rats were given goat IgG or IL-10Ab before being treated with
      CHX (CHX group or IL-10Ab/CHX group). In the CHX group, the CHX treatment
      markedly induced hepatic mRNA and serum protein levels of IL-10. The up
      regulation of IL-10 was significantly suppressed in the IL-10Ab/CHX group.
      Blocking IL-10 in the IL-10Ab/CHX group led to greater increases in hepatic mRNA
      and serum levels of proinflammatory cytokines, such as TNF-alpha and IL-6. The IL
      10Ab/CHX group developed more severe hepatocellular apoptosis, neutrophil
      transmigration, and necrotic change of hepatocytes compared with the CHX group.
      The caspase activities and mRNA levels of Cc120, LOX-1, and E-selectin in the
      livers were significantly higher in the IL-10Ab/CHX group than the CHX group.
      These results demonstrate that IL-10 plays an important role in counteracting the
      effect of proinflammatory cytokines, such as a TNF signaling cascade, and in
      attenuating the CHX-induced liver injury.

PMID- 19395593
TI  - IC50-to-Ki: a web-based tool for converting IC50 to Ki values for inhibitors of
      enzyme activity and ligand binding.
AB  - A new web-server tool estimates K(i) values from experimentally determined IC(50)
      values for inhibitors of enzymes and of binding reactions between macromolecules
      (e.g. proteins, polynucleic acids) and ligands. This converter was developed to
      enable end users to help gauge the quality of the underlying assumptions used in
      these calculations which depend on the type of mechanism of inhibitor action and
      the concentrations of the interacting molecular species. Additional calculations
      are performed for nonclassical, tightly bound inhibitors of enzyme-substrate or
      of macromolecule-ligand systems in which free, rather than total concentrations
      of the reacting species are required. Required user-defined input values include
      the total enzyme (or another target molecule) and substrate (or ligand)
      concentrations, the K(m) of the enzyme-substrate (or the K(d) of the target
      ligand) reaction, and the IC(50) value. Assumptions and caveats for these
      calculations are discussed along with examples taken from the literature. The
      host database for this converter contains kinetic constants and other data for
      inhibitors of the proteolytic clostridial neurotoxins
      (http://botdb.abcc.ncifcrf.gov/toxin/kiConverter.jsp).

PMID- 19395592
TI  - Both helix topology and counterion distribution contribute to the more effective
      charge screening in dsRNA compared with dsDNA.
AB  - The recent discovery of the RNA interference mechanism emphasizes the biological
      importance of short, isolated, double-stranded (ds) RNA helices and calls for a
      complete understanding of the biophysical properties of dsRNA. However, most
      previous studies of the electrostatics of nucleic acid duplexes have focused on
      DNA. Here, we present a comparative investigation of electrostatic effects in RNA
      and DNA. Using resonant (anomalous) and non-resonant small-angle X-ray
      scattering, we characterized the charge screening efficiency and counterion
      distribution around short (25 bp) dsDNA and RNA molecules of comparable sequence.
      Consistent with theoretical predictions, we find counterion mediated screening to
      be more efficient for dsRNA than dsDNA. Furthermore, the topology of the RNA A
      form helix alters the spatial distribution of counterions relative to B-form DNA.
      The experimental results reported here agree well with ion-size-corrected non
      linear Poisson-Boltzmann calculations. We propose that differences in
      electrostatic properties aid in selective recognition of different types of short
      nucleic acid helices by target binding partners.

PMID- 19395594
TI  - IHF-binding sites inhibit DNA loop formation and transcription initiation.
AB  - Transcriptional activation of enhancer and sigma(54)-dependent promoters requires
      efficient interactions between enhancer-binding proteins (EBP) and promoter bound
      sigma(54)-RNA polymerase (E sigma(54)) achieved by DNA looping, which is usually
      facilitated by the integration host factor (IHF). Since the lengths of the
      intervening region supporting DNA-loop formation are similar among IHF-dependent
      and IHF-independent promoters, the precise reason(s) why IHF is selectively
      important for the frequency of transcription initiation remain unclear. Here,
      using kinetic cyclization and in vitro transcription assays we show that, in the
      absence of IHF protein, the DNA fragments containing an IHF-binding site have
      much less looping-formation ability than those that lack an IHF-binding site.
      Furthermore, when an IHF consensus-binding site was introduced into the
      intervening region between promoter and enhancer of the target DNA fragments,
      loop formation and DNA-loop-dependent transcriptional activation are
      significantly reduced in a position-independent manner. DNA-looping-independent
      transcriptional activation was unaffected. The binding of IHF to its consensus
      site in the target promoters clearly restored efficient DNA looping formation and
      looping-dependent transcriptional activation. Our data provide evidence that one
      function for the IHF protein is to release a communication block set by intrinsic
      properties of the IHF DNA-binding site.

PMID- 19395595
TI  - Identification of HCV protease inhibitor resistance mutations by selection
      pressure-based method.
AB  - A major challenge to successful antiviral therapy is the emergence of drug
      resistant viruses. Recent studies have developed several automated analyses of
      HIV sequence polymorphism based on calculations of selection pressure (K(a)/K(s))
      to predict drug resistance mutations. Similar resistance analysis programs for
      HCV inhibitors are not currently available. Taking advantage of the recently
      available sequence data of patient HCV samples from a Phase II clinical study of
      protease inhibitor boceprevir, we calculated the selection pressure for all
      codons in the HCV protease region (amino acid 1-181) to identify potential
      resistance mutations. The correlation between mutations was also calculated to
      evaluate linkage between any two mutations. Using this approach, we identified
      previously known major resistant mutations, including a recently reported
      mutation V55A. In addition, a novel mutation V158I was identified, and we further
      confirmed its resistance to boceprevir in protease enzyme and replicon assay. We
      also extended the approach to analyze potential interactions between individual
      mutations and identified three pairs of correlated changes. Our data suggests
      that selection pressure-based analysis and correlation mapping could provide
      useful tools to analyze large amount of sequencing data from clinical samples and
      to identify new drug resistance mutations as well as their linkage and
      correlations.

PMID- 19395597
TI  - Uses and abuses of the Hare Psychopathy Checklist.

PMID- 19395596
TI  - ProteinCCD: enabling the design of protein truncation constructs for expression
      and crystallization experiments.
AB  - ProteinCCD (CCD for Crystallographic Construct Design) aims to facilitate a
      common practice in structural biology, namely the design of several truncation
      constructs of the protein under investigation, based on experimental data or on
      sequence analysis tools. ProteinCCD functions as a meta-server, available online
      at http://xtal.nki.nl/ccd, that collects information from prediction servers
      concerning secondary structure, disorder, coiled coils, transmembrane segments,
      domains and domain linkers. It then displays a condensed view of all results
      against the protein sequence. The user can study the output and choose
      interactively possible starts and ends for suitable protein constructs. Since the
      required input to ProteinCCD is the DNA and not the protein sequence, once the
      starts and ends of constructs are chosen, the software can automatically design
      the oligonucleotides needed for PCR amplification of all constructs. ProteinCCD
      outputs a comprehensive view of all constructs and all oligos needed for
      bookkeeping or for direct copy-paste ordering of the designed oligonucleotides.

PMID- 19395598
TI  - Economic evaluations in evidence based healthcare.

PMID- 19395600
TI  - Review: positive psychological well-being reduces the risk of mortality in both
      ill and healthy populations.

PMID- 19395601
TI  - One-third of the excess death rate in 15-54 year olds in Scotland due to problem
      drug use.

PMID- 19395602
TI  - Early response to treatment predicts remission and recovery at 3 years in people
      with schizophrenia.

PMID- 19395603
TI  - The 3 item anxiety subscale of the Edinburgh Postpartum Depression Scale may
      detect postnatal depression as well as the 10 item full scale.

PMID- 19395604
TI  - CBT improves maternal perinatal depression in rural Pakistan.

PMID- 19395605
TI  - Brief behavioural intervention for infant sleep problems reduces depression in
      mothers.

PMID- 19395606
TI  - School based intervention improves PTSD symptoms in children affected by
      political violence.

PMID- 19395607
TI  - Family focused therapy shortens recovery time from depression but not mania in
      adolescents with bipolar disorder.

PMID- 19395608
TI  - Review: long term use of antidepressants for bipolar disorder reduces depressive
      episodes but increases risk of mania.

PMID- 19395609
TI  - Switching to aripiprazole from olanzapine leads to weight loss in overweight
      people with schizophrenia or schizoaffective disorder.

PMID- 19395610
TI  - Refractory schizophrenia: adding aripiprazole to clozapine reduces negative but
      not overall symptoms.

PMID- 19395611
TI  - Review: non-pharmacological interventions reduce antipsychotic induced weight
      gain.

PMID- 19395612
TI  - Individual placement and support improves employment of young people with first
      episode psychosis.

PMID- 19395613
TI  - Agomelatine improves symptoms of generalised anxiety disorder.

PMID- 19395614
TI  - Adjunctive transdermal oestradiol improves positive symptoms and general
      psychopathology in women with schizophrenia.

PMID- 19395615
TI  - Review: long term psychodynamic psychotherapy improves outcomes in people with
      complex mental disorders.

PMID- 19395616
TI  - Physical activity improves cognitive function in people with memory impairment.

PMID- 19395617
TI  - Starting a conventional antipsychotic increases risk of death more than an
      atypical antipsychotic in elderly people with dementia.

PMID- 19395618
TI  - Advanced paternal age increases risk of bipolar disorder in offspring.

PMID- 19395619
TI  - Combat exposure increases risk of alcohol misuse in military personnel following
      deployment.

PMID- 19395620
TI  - Small for gestational age boys at increased risk of later psychiatric
      hospitalisation.

PMID- 19395622
TI  - Pervasive behavioural problems are common in children born at less than 26 weeks
      of gestation.

PMID- 19395621
TI  - Attention disturbances are associated with low birth weight in an urban community
      but not a suburban community.

PMID- 19395623
TI  - Low recognition of depression among outpatients by internists in China.

PMID- 19395624
TI  - Use of focus group data to develop recommendations for demographically segmented
      colorectal cancer educational strategies.
AB  - Screening is available and effective in colorectal cancer (CRC) control, but
      underutilized. The purpose of this study was to use focus group data to develop
      recommendations for the development of educational interventions to increase CRC
      screening, using an audience segmentation strategy. Demographic segments were
      based on urban-rural residence, race (African-American, White) and sex. One
      hundred and sixty-five participants age 50+, with no history of CRC participated
      in 17 focus groups in Alabama urban and rural communities. Transcripts were
      examined by independent coders. Knowledge among participants was limited
      regarding age to begin screening, insurance coverage and risk factors for CRC.
      Perceived barriers to screening included lack of physician recommendation,
      cost/lack of insurance coverage, pain/discomfort and embarrassment. African
      American men reported postponement in seeing their physicians. White women were
      proactive at initiating discussion of CRC screening with their providers while
      African-American women felt that providers should drive the process. No urban
      rural differences were identified. This study identified cultural and gender
      characteristics and perceptions that can be used in the development of
      demographically segmented health communication interventions to increase CRC
      awareness and screening.

PMID- 19395626
TI  - Interpretation of the glaucoma "landmark studies".

PMID- 19395628
TI  - An uncommon case with intravitreal worm. Intravitreal Dirofilaria infection.

PMID- 19395629
TI  - Diffuse unilateral subacute neuroretinitis masquerading as a white-dot syndrome.

PMID- 19395632
TI  - Ocular telemedicine between Nepal and the USA: prevalence of vitreoretinal
      disease in rural Nepal.
AB  - This study is aimed at reporting experiences with telemedicine between Nepal and
      the USA and at reporting the prevalence of age-related macular degeneration (AMD)
      and diabetic retinopathy (DR) in rural Nepal. AMD and DR are becoming more
      significant factors for non-reversible vision loss in rural Nepal due to
      increasing life expectancy and urbanisation. The prevalence of DM is low compared
      with the developed world, but the percentage of diabetics with DR is high,
      presumably due to limited access to healthcare. The higher prevalence of DM in
      Hetauda is explained as being due to a more urban lifestyle, dietary habits (more
      deep-fried food) and more advanced age.

PMID- 19395633
TI  - The influence of disease severity on quality of eye-drop administration in
      patients with glaucoma or ocular hypertension.

PMID- 19395634
TI  - Swimming goggles and elevated intraocular pressure.

PMID- 19395635
TI  - Delayed fellow eye involvement in patients with Vogt-Koyanagi-Harada disease.

PMID- 19395636
TI  - Insights into neural crest migration and differentiation from experimental
      embryology.
AB  - In this essay, I discuss two studies published in the Journal of Experimental
      Embryology and Morphology that represent how experimental embryologists began to
      deal with the issue of the vertebrate body plan. In one such study by Nicole Le
      Douarin and Marie-Aimee Teillet, the neural crest was unequivocally identified as
      being the origin of the chick enteric nervous system through careful chimeric
      experiments and histological analyses. In the second, Michael Rickmann and
      colleagues showed how to combine immunohistochemical and experimental techniques
      in a study of the segmental patterning of the spinal nerves of the chick embryo.

PMID- 19395637
TI  - Stem cells, signals and vertebrate body axis extension.
AB  - The progressive generation of chick and mouse axial tissues - the spinal cord,
      skeleton and musculature of the body - has long been proposed to depend on the
      activity of multipotent stem cells. Here, we evaluate evidence for the existence
      and multipotency of axial stem cells. We show that although the data strongly
      support their existence, there is little definitive information about their
      multipotency or extent of contribution to the axis. We also review the location
      and molecular characteristics of these putative stem cells, along with their
      evolutionary conservation in vertebrates and the signalling mechanisms that
      regulate and arrest axis extension.

PMID- 19395638
TI  - Floral stem cell termination involves the direct regulation of AGAMOUS by
      PERIANTHIA.
AB  - In Arabidopsis, the population of stem cells present in young flower buds is lost
      after the production of a fixed number of floral organs. The precisely timed
      repression of the stem cell identity gene WUSCHEL (WUS) by the floral homeotic
      protein AGAMOUS (AG) is a key part of this process. In this study, we report on
      the identification of a novel input into the process of floral stem cell
      regulation. We use genetics and chromatin immunoprecipitation assays to
      demonstrate that the bZIP transcription factor PERIANTHIA (PAN) plays a role in
      regulating stem cell fate by directly controlling AG expression and suggest that
      this activity is spatially restricted to the centermost region of the AG
      expression domain. These results suggest that the termination of floral stem cell
      fate is a multiply redundant process involving loci with unrelated floral
      patterning functions.

PMID- 19395639
TI  - Dual roles of the bZIP transcription factor PERIANTHIA in the control of floral
      architecture and homeotic gene expression.
AB  - Flowers develop from floral meristems, which harbor stem cells that support the
      growth of floral organs. The MADS domain transcription factor AGAMOUS (AG) plays
      a central role in floral patterning and is required not only for the
      specification of the two reproductive organ types, but also for termination of
      stem cell fate. Using a highly conserved cis-regulatory motif as bait, we
      identified the bZIP transcription factor PERIANTHIA (PAN) as a direct regulator
      of AG in Arabidopsis. PAN and AG expression domains overlap, and mutations in
      either the PAN-binding site or PAN itself abolish the activity of a reporter
      devoid of redundant elements. Whereas under long-day conditions pan mutants have
      merely altered floral organ number, they display in addition typical AG loss-of
      function phenotypes when grown under short days. Consistently, we found reduced
      AG RNA levels in these flowers. Finally, we show that PAN expression persists in
      ag mutant flowers, suggesting that PAN and AG are engaged in a negative-feedback
      loop, which might be mediated by the stem-cell-inducing transcription factor
      WUSCHEL (WUS).

PMID- 19395640
TI  - Mutations in zebrafish leucine-rich repeat-containing six-like affect cilia
      motility and result in pronephric cysts, but have variable effects on left-right
      patterning.
AB  - Cilia defects have been implicated in a variety of human diseases and genetic
      disorders, but how cilia motility contributes to these phenotypes is still
      unknown. To further our understanding of how cilia function in development, we
      have cloned and characterized two alleles of seahorse, a zebrafish mutation that
      results in pronephric cysts. seahorse encodes Lrrc6l, a leucine-rich repeat
      containing protein that is highly conserved in organisms that have motile cilia.
      seahorse is expressed in zebrafish tissues known to contain motile cilia.
      Although mutants do not affect cilia structure and retain the ability to interact
      with Disheveled, both alleles of seahorse strongly affect cilia motility in the
      zebrafish pronephros and neural tube. Intriguingly, although seahorse mutations
      variably affect fluid flow in Kupffer's vesicle, they can have very weak effects
      on left-right patterning. Combined with recently published results, our alleles
      suggest that the function of seahorse in cilia motility is separable from its
      function in other cilia-related phenotypes.

PMID- 19395641
TI  - Distinct phases of cardiomyocyte differentiation regulate growth of the zebrafish
      heart.
AB  - Amongst animal species, there is enormous variation in the size and complexity of
      the heart, ranging from the simple one-chambered heart of Ciona intestinalis to
      the complex four-chambered heart of lunged animals. To address possible
      mechanisms for the evolutionary adaptation of heart size, we studied how growth
      of the simple two-chambered heart in zebrafish is regulated. Our data show that
      the embryonic zebrafish heart tube grows by a substantial increase in
      cardiomyocyte number. Augmented cardiomyocyte differentiation, as opposed to
      proliferation, is responsible for the observed growth. By using transgenic assays
      to monitor developmental timing, we visualized for the first time the dynamics of
      cardiomyocyte differentiation in a vertebrate embryo. Our data identify two
      previously unrecognized phases of cardiomyocyte differentiation separated in
      time, space and regulation. During the initial phase, a continuous wave of
      cardiomyocyte differentiation begins in the ventricle, ends in the atrium, and
      requires Islet1 for its completion. In the later phase, new cardiomyocytes are
      added to the arterial pole, and this process requires Fgf signaling. Thus, two
      separate processes of cardiomyocyte differentiation independently regulate growth
      of the zebrafish heart. Together, our data support a model in which modified
      regulation of these distinct phases of cardiomyocyte differentiation has been
      responsible for the changes in heart size and morphology among vertebrate
      species.

PMID- 19395642
TI  - Defining retinal progenitor cell competence in Xenopus laevis by clonal analysis.
AB  - Extrinsic cues and intrinsic competence act in concert for cell fate
      determination in the developing vertebrate retina. However, what controls
      competence and how precise is the control are largely unknown. We studied the
      regulation of competence by examining the order in which individual retinal
      progenitor cells (RPCs) generate daughters. Experiments were performed in Xenopus
      laevis, whose full complement of retinal cells is formed in 2 days. We lineage
      labeled RPCs at the optic vesicle stage. Subsequently we administered a cell
      cycle marker, 5-bromodeoxyuridine (BrdU) at early, middle or late periods of
      retinogenesis. Under these conditions, and in this animal, BrdU is not cleared by
      the time of analysis, allowing cumulative labeling. All retinal cell types were
      generated throughout nearly the entire retinogenesis period. When we examined the
      order that individual RPCs generated daughters, we discovered a regular and
      consistent sequence according to phenotype: RGC, Ho, CPr, RPr, Am, BP, MG. The
      precision of the order between the clones supports a model in which RPCs proceed
      through stepwise changes in competence to make each cell type, and do so
      unidirectionally. Because every cell type can be generated simultaneously within
      the same retinal environment, the change in RPC competence is likely to be
      autonomous.

PMID- 19395643
TI  - Comorbidity/overlapping between ADHD and PTSD in relation to IQ among children of
      traumatized/non-traumatized parents.
AB  - OBJECTIVE: This study explores the comorbidity between symptoms of ADHD and PTSD
      in relation to IQ among refugee children of traumatized parents (TP) and non
      traumatized parents (NTP). METHOD: The study compares 80 refugee children, 40
      with TP with 40 with NTP. ADHD and PTSD are assessed using DICA. Children's
      cognitive functions are measured by WISC. Teacher ratings of YCI and SDQ are
      performed. RESULTS: Overlapping between ADHD and PTSD symptoms are represented
      among children with TP. Cognitive functions, related to ADHD and PTSD, reveal
      associations between low IQ (<84) and having both ADHD and PTSD among children
      with TP. CONCLUSIONS: Concerns are raised about how ADHD and PTSD symptoms in a
      child are to be interpreted. Some overlapping exists between the two syndromes,
      but further studies should determine whether true comorbidity exists between ADHD
      and PTSD symptoms to better understand how to correctly diagnose and treat
      refugee children with TP.

PMID- 19395644
TI  - Behavioral approach in ADHD: testing a motivational dysfunction hypothesis.
AB  - OBJECTIVE: Etiological models of attention-deficit hyperactivity disorder (ADHD)
      increasingly support the role of a motivational dysfunction pathway, particularly
      for hyperactive-impulsive symptoms. Overactive behavioral approach tendencies are
      implicated among these motivational accounts. However, other externalizing
      disorder symptoms, such as the psychopathy dimension, are also associated with
      behavioral approach and frequently co-occur with ADHD. The current study tested
      the hypothesis that behavioral approach is differentially associated with
      hyperactive-impulsive ADHD and psychopathy symptoms. METHOD: A sample of young
      adults ( n = 220) completed self-report measures assessing behavioral approach
      and inhibition, ADHD symptoms, and psychopathy symptoms. RESULTS: Structural
      equation analyses supported the hypothesis that behavioral approach predicts
      hyperactive-impulsive ADHD symptoms while considering symptom overlap with
      psychopathy symptoms. CONCLUSION: These findings support motivational accounts
      that behavioral approach tendencies are predictive of ADHD symptoms and address
      concerns about externalizing comorbidity. Implications for ADHD etiology are
      discussed.

PMID- 19395645
TI  - Memory for object locations in boys with and without ADHD.
AB  - OBJECTIVE: To determine whether 7- to 12-year-old boys with ADHD, relative to non
      ADHD age-mates, exhibit greater difficulty learning and remembering object
      locations. The second purpose was to examine the functional utility of mnemonic
      strategies, specifically speech-to-self, used by boys with and without ADHD.
      METHOD: Boys with and without ADHD were videotaped while completing a well
      established, laboratory-based object location learning and memory task. RESULTS:
      Boys with ADHD evinced a deficit while learning the location of objects and
      employed less sophisticated forms of private speech during the memory task.
      CONCLUSION: These findings reveal details about the utility of private speech
      during spatial working memory performance and further a theoretical understanding
      of ADHD. (J. of Att. Dis. 2010; 13(5) 505-515).

PMID- 19395646
TI  - Usefulness of a clinician rating scale in identifying preschool children with
      ADHD.
AB  - OBJECTIVE: To ascertain the psychometric properties and clinical utility of the
      Behavioral Rating Inventory for Children (BRIC), a novel clinician inventory for
      preschoolers. METHOD: Completion of the BRIC for 214 preschoolers follows 2
      evaluation sessions, generally separated by less than 2 weeks. Items are
      submitted to a Principal Components Analysis (PCA) with Varimax rotation. Test
      retest reliability and validity relative to other measures are assessed. RESULTS:
      PCA yields a 2-factor solution representing a "Symptom Triad" and a
      "Mood/Sociability Factor." Test-retest reliability of the triad and factor are
      .78 (p <.001) and .55 (p < .001), respectively. Correlations between parent and
      teacher ratings of ADHD-related behaviors and the Symptom Triad range from .39
      .47 (all p <.001); similar correlations are found with laboratory measures of
      activity level (r = .35-.49, all p <.001). CONCLUSION: The Symptom Triad of the
      BRIC appears to be a reliable and valid tool that may assist researchers and
      clinicians in studying and diagnosing ADHD in preschoolers, particularly in cases
      where teacher ratings are unavailable. J. of Att. Dis. 2010; 13(5) 479-488.

PMID- 19395647
TI  - Life impairments in adults with medication-treated ADHD.
AB  - OBJECTIVE: In developing psychosocial approaches to augment outcomes for
      medication-treated adults with ADHD, it is important to understand what types of
      life-impairments are most affected by continued ADHD symptoms that occur despite
      medication treatment. This may assist in delineating targets for interventions,
      as well as assessments of functional outcomes that are sensitive to change in
      this population. METHOD: The sample consists of 105 adults with ADHD presenting
      for entry into clinical trials of CBT for residual ADHD. Life impairments are
      rated by a clinician using the LIFE-RIFT, which has subscales for work
      impairment, interpersonal impairment, life-satisfaction, and recreation, ADHD
      symptoms using the ADHD Rating Scale, overall ADHD severity using the clinical
      global impression, and associated distress using the Hamilton Depression and
      Anxiety Rating Scales. RESULTS: The most problematic impairments are in the
      domain of work, followed by interpersonal. Generally, the subscales of the LIFE
      RIFT are associated, at the bivariate level, with all 4 symptom indices. Work and
      interpersonal impairments are uniquely associated with overall severity of ADHD
      symptoms using both the CGI and the ADHD Rating Scale. However interpersonal and
      life-satisfaction impairments are uniquely associated with depression, and life
      satisfaction is uniquely associated with anxiety. CONCLUSION: In medication
      treated adults with ADHD, work and interpersonal impairments appear to be the
      most problematic areas of life-impairment, which are uniquely associated with
      ADHD severity. Life-satisfaction appears to be uniquely associated with distress
      as defined by anxiety and depression symptoms, with interpersonal impairments
      also playing a role. Psychosocial treatments for medication treated adults should
      target work and interpersonal domains and should include skills for managing
      associated distress.

PMID- 19395648
TI  - Effects of extended-release guanfacine on ADHD symptoms and sedation-related
      adverse events in children with ADHD.
AB  - OBJECTIVE: Guanfacine extended release (GXR) is a selective alpha(2A)
      adrenoceptor agonist that is shown to be an effective nonstimulant treatment for
      the symptoms of attention-deficit/hyperactivity disorder. This report documents
      the time course and predictors of symptom efficacy and sedation-related adverse
      events (AEs) that emerge during GXR treatment throughout 3 randomized, placebo
      controlled, double-blind trials of the drug. METHOD: Analysis of data from 3 GXR
      clinical trials. RESULTS: Few variables related to the study participants or
      their treatment regimen affects the emergence or magnitude of sedation-related
      AEs. The best predictor of sedation is treatment duration, with the likelihood of
      sedation-related AEs decreasing with increasing time on medication. Sedation
      related AEs are not predicted by the actual dose a participant receives, the
      magnitude of any dose changes, or the relationship between dose received and the
      magnitude of dose changes. Rates of discontinuation because of sedation-related
      side effects average 6.3% for GXR-treated participants and 0.5% for placebo
      treated participants across the three trials. CONCLUSION: These results suggest
      that acclimation to GXR may minimize the risk for, and magnitude of, sedation
      related AEs. (J. of Att. Dis. 2010; 13(5) 532-538).

PMID- 19395649
TI  - What can family physicians contribute in palliative home care in Taiwan?
AB  - BACKGROUND: Family physicians in Taiwan have expressed low willingness to provide
      palliative home care. OBJECTIVE: To explore the medical needs of terminal cancer
      patients in home care and thus clarify the role and tasks of family physicians in
      providing palliative home care. METHODS: Seventy-seven terminal cancer patients
      discharged from a palliative care unit from July 2003 to July 2004 who had
      received family physician home visits were enrolled. A structured assessment form
      was applied to each visit. RESULTS: Under the collaboration by the palliative
      home care team and family physicians, the average interval from discharge to the
      first physician visit was 20.3 days and the average interval between physician
      visits was 37.9 days. The patients had an average of 5.9 active medical problems:
      the most frequent problem was pain (58.4%), followed by anorexia (42.9%) and
      constipation (42.9%). Forty-four patients (58.7%) died at home, while 31 patients
      (41.3%) eventually died in the hospital. Through multiple logistic regression
      analysis, patients who had never been rehospitalized [odds ratio (OR) = 12.95,
      95% confidence interval (CI) = 3.41-49.19], who preferred to die at home (OR =
      4.68, 95% CI = 1.21-18.09) and who were most functionally dependent with an
      Eastern Cooperative Oncology Group scale = 4 (OR = 4.36, 95% CI = 1.02-18.64)
      were found to be most likely to die at home under this care model. CONCLUSION:
      Through palliative home care with the participation of family physicians,
      patients' preference could be a significant determinant of home death. Our
      finding can be helpful to the establishment of an ethical care model for terminal
      cancer patients.

PMID- 19395650
TI  - Angiogenic monocytes: another colorful blow to endothelial progenitors.
AB  - This Commentary provides perspective on a related article by Sun-Jin Kim and
      coworkers (Am J Pathol: 172 AJP08-0819), who assess the contribution of bone
      marrow-derived cells to tumor angiogenesis in a physiologic, non-myeloablative
      setting and conclude that the actual angiogenic cell type incorporated in the
      newly formed vessels is actually monocytes/macrophages.

PMID- 19395651
TI  - Caveolin-1 (P132L), a common breast cancer mutation, confers mammary cell
      invasiveness and defines a novel stem cell/metastasis-associated gene signature.
AB  - Here we used the Met-1 cell line in an orthotopic transplantation model in FVB/N
      mice to dissect the role of the Cav-1(P132L) mutation in human breast cancer.
      Identical experiments were performed in parallel with wild-type Cav-1. Cav
      1(P132L) up-regulated the expression of estrogen receptor-alpha as predicted,
      because only estrogen receptor-alpha-positive patients have been shown to harbor
      Cav-1(P132L) mutations. In the context of primary tumor formation, Cav-1(P132L)
      behaved as a loss-of-function mutation, lacking any tumor suppressor activity. In
      contrast, Cav-1(P132L) caused significant increases in cell migration, invasion,
      and experimental metastasis, consistent with a gain-of-function mutation. To
      identify possible molecular mechanism(s) underlying this invasive gain-of
      function activity, we performed unbiased gene expression profiling. From this
      analysis, we show that the Cav-1(P132L) expression signature contains numerous
      genes that have been previously associated with cell migration, invasion, and
      metastasis. These include i) secreted growth factors and extracellular matrix
      proteins (Cyr61, Plf, Pthlh, Serpinb5, Tnc, and Wnt10a), ii) proteases that
      generate EGF and HGF (Adamts1 and St14), and iii) tyrosine kinase substrates and
      integrin signaling/adapter proteins (Akap13, Cdcp1, Ddef1, Eps15, Foxf1a, Gab2,
      Hs2st1, and Itgb4). Several of the P132L-specific genes are also highly expressed
      in stem/progenitor cells or are associated with myoepithelial cells, suggestive
      of an epithelial-mesenchymal transition. These results directly support clinical
      data showing that patients harboring Cav-1 mutations are more likely to undergo
      recurrence and metastasis.

PMID- 19395652
TI  - PTEN deficiency is fully penetrant for prostate adenocarcinoma in C57BL/6 mice
      via mTOR-dependent growth.
AB  - The tumor suppressor phosphatase and tensin homolog (PTEN) is frequently involved
      in human prostate carcinoma. PTEN is therefore an attractive target for the
      development of preclinical animal models. Prostate intraepithelial neoplasia
      lesions develop in mice with Pten heterozygosity, but disease progression has
      been reported only in combination with either other tumor suppressor gene
      alterations or the conditional inactivation of both Pten alleles in prostate
      epithelial cells. We report that on a C57BL/6 background, in contrast to previous
      studies on mixed 129 genetic backgrounds, Pten locus heterozygosity is fully
      penetrant for the development of prostate adenocarcinoma. Grossly observable
      tumors were detected at 6 months of age, and, by 10 to 12 months, 100% of
      examined mice developed adenocarcinoma of the anterior prostate. Furthermore,
      double heterozygotes carrying both Pten and Tsc2-null alleles showed no increase
      relative to Pten(+/-) heterozygotes in either lesion development or progression.
      Lesions in both Pten(+/-); Tsc2(+/-), and Pten(+/-) mice exhibited loss of PTEN
      expression and activation of PI3K signaling. PI3K activation occurred early in
      prostate intraepithelial neoplasia lesion formation in these animals, consistent
      with loss of PTEN function, and contributed to the etiology of tumors that
      developed in Pten(+/-) mice. Furthermore, prostate lesion growth in Pten(+/-)
      mice was dependent on mTOR, as evidenced by a reduction in both phospho-S6 levels
      and proliferative index after rapamycin treatment.

PMID- 19395653
TI  - Dietary flavonoid fisetin induces a forced exit from mitosis by targeting the
      mitotic spindle checkpoint.
AB  - Fisetin is a natural flavonol present in edible vegetables, fruits and wine at 2
      160 microg/g concentrations and an ingredient in nutritional supplements with
      much higher concentrations. The compound has been reported to exert
      anticarcinogenic effects as well as antioxidant and anti-inflammatory activity
      via its ability to act as an inhibitor of cell proliferation and free radical
      scavenger, respectively. Our cell-based high-throughput screen for small
      molecules that override chemically induced mitotic arrest identified fisetin as
      an antimitotic compound. Fisetin rapidly compromised microtubule drug-induced
      mitotic block in a proteasome-dependent manner in several human cell lines.
      Moreover, in unperturbed human cancer cells fisetin caused premature initiation
      of chromosome segregation and exit from mitosis without normal cytokinesis. To
      understand the molecular mechanism behind these mitotic errors, we analyzed the
      consequences of fisetin treatment on the localization and phoshorylation of
      several mitotic proteins. Aurora B, Bub1, BubR1 and Cenp-F rapidly lost their
      kinetochore/centromere localization and others became dephosphorylated upon
      addition of fisetin to the culture medium. Finally, we identified Aurora B kinase
      as a novel direct target of fisetin. The activity of Aurora B was significantly
      reduced by fisetin in vitro and in cells, an effect that can explain the observed
      forced mitotic exit, failure of cytokinesis and decreased cell viability. In
      conclusion, our data propose that fisetin perturbs spindle checkpoint signaling,
      which may contribute to the antiproliferative effects of the compound.

PMID- 19395654
TI  - A2A adenosine receptor deficiency leads to impaired tracheal relaxation via NADPH
      oxidase pathway in allergic mice.
AB  - A(2A) adenosine receptor (A(2A)AR) has been shown to suppress superoxide
      generation in leukocytes via the cAMP-protein kinase A (PKA) pathway. However, no
      study has yet explored the role of A(2A)AR in relation to NADPH oxidase in murine
      tracheas in vitro, which may lead to altered smooth muscle relaxation in asthma.
      Therefore, the present study evaluated the effects of A(2A)AR deficiency on the
      NADPH oxidase pathway in tracheas of A(2A) wild-type (WT) and A(2A) knockout (KO)
      mice. A(2A)WT mice were sensitized with ovalbumin (30 microg i.p.) on days 1 and
      6, followed by 5% ovalbumin aerosol challenge on days 11, 12, and 13. A(2A)AR
      (gene and protein expression), cAMP, and phosphorylated PKA (p-PKA) levels were
      decreased in A(2A)WT sensitized mice compared with controls. A(2A)KO mice also
      showed decreased cAMP and p-PKA levels. A(2A)WT sensitized and A(2A)KO control
      mice had increased gene and protein expression of NADPH oxidase subunits (p47phox
      and gp91phox) compared with the controls. Tracheal relaxation to specific A(2A)AR
      agonist, 4-[2-[[6-amino-9-(N-ethyl-beta-d-ribofuranuronamidosyl)-9H-purin-2
      yl]amino]ethyl]benzenepropanoic acid hydrochloride (CGS 21680), decreased in
      A(2A)WT sensitized mice compared with the controls, although it was absent in
      A(2A)KO mice. Pretreatment with NADPH oxidase inhibitors
      apocyanin/diphenyliodonium reversed the attenuated relaxation to CGS 21680 in
      A(2A)WT sensitized tracheas, whereas specific PKA inhibitor (9S,10S,12R)
      2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3
      fg:3',2',1'-kl]pyrrolo[3,4-i] [1,6]benzodiazocine-10-carboxylic acid hexyl ester
      (KT 5720) blocked CGS 21680-induced relaxation. Tracheal reactive oxygen species
      (ROS) generation was also increased in A(2A)WT sensitized and A(2A)KO control
      mice compared with the controls. In conclusion, this study shows that A(2A)AR
      deficiency causes increased NADPH oxidase activation leading to decreased
      tracheal relaxation via altered cAMP-PKA signaling and ROS generation.

PMID- 19395655
TI  - A comparative genomics approach identifies a PPR-DYW protein that is essential
      for C-to-U editing of the Arabidopsis chloroplast accD transcript.
AB  - Several nuclear-encoded proteins containing pentatricopeptide repeat (PPR) motifs
      have previously been identified to be trans-factors essential for particular
      chloroplast RNA editing events through analysis of mutants affected in
      chloroplast biogenesis or function. Other PPR genes are known to encode proteins
      involved in other aspects of organelle RNA metabolism. A function has not been
      assigned to most members of the large plant PPR gene family. Arabidopsis and rice
      each contain over 400 PPR genes, of which about a fifth exhibit a C-terminal DYW
      domain. We describe here a comparative genomics approach that will facilitate
      identification of the role of RNA-binding proteins in organelle RNA metabolism.
      We have implemented this strategy to identify an Arabidopsis nuclear-encoded gene
      RARE1 that is required for editing of the chloroplast accD transcript. RARE1
      carries 15 PPR motifs, an E/E+ and a DYW domain, whereas previously reported
      editing factors CRR4, CRR21, and CLB19 lack a DYW domain. The accD gene encodes
      the beta carboxyltransferase subunit of acetyl coA carboxylase, which catalyzes
      the first step in fatty acid biosynthesis in chloroplasts. Despite a lack of accD
      C794 editing and lack of restoration of an evolutionarily conserved leucine
      residue in the beta carboxyltransferase protein, rare1 mutants are unexpectedly
      robust and reproduce under growth room conditions. Previously the serine-to
      leucine alteration caused by editing was deemed essential in the light of the
      finding that a recombinantly expressed "unedited" form of the pea acetyl coA
      carboxylase was catalytically inactive.

PMID- 19395656
TI  - The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7
      expression.
AB  - Recent genome-wide scans for colorectal cancer (CRC) have revealed the SMAD7
      (mothers against decapentaplegic homolog 7) gene as a locus associated with a
      modest, but highly significant increase in CRC risk. To identify the causal basis
      of the association between 18q21 variation and CRC, we resequenced the 17-kb
      region of linkage disequilibrium and evaluated all variants in 2532 CRC cases and
      2607 controls. A novel C to G single nucleotide polymorphism (SNP) at 44,703,563
      bp was maximally associated with CRC risk (P = 5.98 x 10(-7); > or =1.5-fold more
      likely to be causal than other variants). Using transgenic assays in Xenopus
      laevis as a functional model, we demonstrate that the G risk allele leads to
      reduced reporter gene expression in the colorectum (P = 5.4 x 10(-3)).
      Electrophoretic mobility shift assays provided evidence for the role of Novel 1
      in transcription factor binding. We propose that the novel SNP we have identified
      is the functional change leading to CRC predisposition through differential SMAD7
      expression and, hence, aberrant TGF-beta signaling.

PMID- 19395657
TI  - Differential adaptations to eccentric versus conventional resistance training in
      older humans.
AB  - We hypothesized that training with eccentric contractions only (therefore using
      higher loads) would yield greater muscle structural and strength gains compared
      with conventional resistance training. Nine older adults (mean +/- s.d. age, 74
      +/- 3 years) were assigned to a conventional (CONV) resistance training group
      performing both concentric and eccentric contractions and 10 (age, 67 +/- 2
      years) to an eccentric-only (ECC) resistance training group. Both groups trained
      three times per week for 14 weeks at 80% of the five-repetition maximum, specific
      to each training mode. Maximal knee extensor torque was assessed during
      isometric, concentric and eccentric contractions across a range of angular
      velocities (0-3.49 rad s(-1)). Vastus lateralis muscle architecture (fascicle
      length, pennation angle and muscle thickness) was assessed in vivo at rest using
      ultrasonography. Training increased fascicle length in both groups, but the
      increase was significantly greater in the ECC (20% increase) than the CONV group
      (8% increase). Conversely, pennation angle significantly increased in the CONV
      (35% increase) but not in the ECC group (5% increase). Muscle thickness increased
      to a similar extent in both groups (approximately 12% increase). In the ECC
      group, eccentric knee extensor torque increased by 9-17% across velocities, but
      concentric torque was unchanged. Conversely, in the CONV group, concentric torque
      increased by 22-37% across velocities, but eccentric torque was unchanged.
      Instead, isometric torque increased to a similar extent in both groups
      (approximately 8% increase). Thus, the two training regimens resulted in
      differential adaptations in muscle architecture and strength. These results
      suggest that the stimulus for adding sarcomeres in-series and in-parallel may be
      different, which implies that different myogenic responses were induced by the
      two different training methods.

PMID- 19395658
TI  - Developmental programming resulting from maternal obesity in mice: effects on
      myocardial ischaemia-reperfusion injury.
AB  - A comprehensive number of epidemiological and animal studies suggest that
      prenatal and early life events are important determinants for disorders later in
      life. Among them, prenatal stress (i.e. stress experienced by the pregnant mother
      with impact on the fetal ontogeny) has clear programming effects on the
      cardiovascular system. A fetus developing in adverse conditions becomes an adult
      who is susceptible to disease, which may include hypertension, insulin
      resistance, altered blood lipid levels and cardiovascular disease. Recent
      evidence demonstrates that maternal programming can occur in the absence of other
      adverse environmental factors. Obesity, which is becoming a problem of large
      proportions in Western countries, is a possible cause of programming. With over
      30% of the population of the USA currently obese, many mothers suffer from
      obesity during their child-bearing years (in fact, these conditions are often
      aggravated during pregnancy). One of the targets of programming is the
      cardiovascular system, and reported consequences include hypertension,
      endothelial dysfunction and vascular abnormalities. The overall goal of our study
      was to investigate the susceptibility of the heart to ischaemia-reperfusion in an
      animal model of maternal obesity. Our data demonstrate that normal (non-mutant)
      offspring from obese agouti mouse dams had an increased susceptibility to
      ischaemia-reperfusion injury. These data may provide insights into the long-term
      cardiovascular consequences of programming.

PMID- 19395659
TI  - Cardiac L-type calcium current is increased in a model of hyperaldosteronism in
      the rat.
AB  - Accumulating evidence supports the importance of aldosterone as an independent
      risk factor in the pathophysiology of cardiovascular disease. It has been
      postulated that aldosterone could contribute to ventricular arrhythmogeneity by
      modulation of cardiac ionic channels. The aim of this study was to analyse ex
      vivo the electrophysiological characteristics of the L-type cardiac calcium
      current (I(CaL)) in a model of hyperaldosteronism in the rat. Aldosterone was
      administered for 3 weeks, and cardiac collagen deposition and haemodynamic
      parameters were analysed. In addition, RT-PCR and patch-clamp techniques were
      applied to study cardiac L-type Ca(2+) channels in isolated cardiomyocytes.
      Administration of aldosterone induced maladaptive cardiac remodelling that was
      related to increased collagen deposition, diastolic dysfunction and cardiac
      hypertrophy. In addition, ventricular myocytes isolated from the aldosterone
      treated group showed increased I(CaL) density and conductance and prolongation of
      the action potential duration. No changes in kinetics or in voltage dependence of
      activation and inactivation of I(CaL) were observed, but relative expression of
      Ca(V)1.2 mRNA levels was higher in cardiomyocytes isolated from the aldosterone
      treated group. The present study demonstrates that aldosterone treatment induces
      myocardial fibrosis, cardiac hypertrophy, increase of I(CaL) density,
      upregulation of L-type Ca(2+) channels and prolongation of action potential
      duration. It could be proposed that aldosterone, through these mechanisms, might
      exert pro-arrhythmic effects in the pathological heart.

PMID- 19395660
TI  - Effect of body posture on postexercise parasympathetic reactivation in men.
AB  - The aim of the present study was to assess the influence of body posture on post
      submaximal exercise parasympathetic reactivation and to examine whether this
      influence was preserved under a heightened sympathetic background. On four
      occasions, eleven moderately trained subjects (22.1 +/- 3.0 years old) performed,
      in random order, two consecutive submaximal running bouts (CTs), each followed by
      5 min passive recovery in an upright (Up), sitting (Sit), supine (Sup) or supine
      with legs up position (SupLu). Between both CTs, participants performed 150 s of
      supramaximal intermittent running (SI). Parasympathetic reactivation was assessed
      from heart rate recovery (HRR) and variability (HRV; e.g. rMSSD(30 s)) indices
      calculated during the 5 min recovery periods [i.e. before (N) and after SI (post
      SI)]. In the N condition, Sup position was associated with a faster and greater
      increase in rMSSD(30 s) than Sit and SupLu (both P < 0.01), which were all higher
      compared with Up (P < 0.001). A 'time' effect was shown in Sit, Sup and SupLu
      (all P < 0.05), but not in Up (P = 0.99). All N values were higher than post-SI
      values (P < 0.001), except for Up, where a trend was apparent (P = 0.06). In the
      post-SI condition, a position effect was preserved for HRR (P < 0.001), but not
      for HRV indices (P = 0.99 for rMSSD(30 s)). In conclusion, the supine position
      accelerated and increased parasympathetic reactivation more than the other three
      positions, but the posture effect was less evident following supramaximal
      exercise. In the context of an accentuated sympathetic background (i.e. post-SI),
      postexercise HRV indices are less gravity dependent than HRR, reflecting more the
      exercise-related changes in parasympathetic activity.

PMID- 19395662
TI  - Glutathione homeostasis in ventricular myocytes from rat hearts with chronic
      myocardial infarction.
AB  - The ubiquitous tripeptide glutathione (GSH) is an essential factor in many
      biological processes, thus its depletion has a major impact on cell function and
      survival. In this study, we examined regulation of GSH in cardiomyocytes under
      chronic oxidative stress elicited by myocardial infarction (MI). Cardiac
      dysfunction was induced in rats by coronary artery ligation, and experiments were
      conducted in myocytes isolated from non-infarcted left ventricle and septum after
      6-8 weeks. Fluorescence microscopy studies using the probe monochlorobimane
      showed that [GSH] in myocytes from post-MI hearts was 42% less than in sham
      control hearts (P < 0.05). However, depleted GSH levels were normalized after 5-6
      h by an insulin mimetic (bis-peroxovanadium-1,10-phenanthroline, bpV(phen); 10
      micromol l(-1)) or by exogenous pyruvate (5 mmol l(-1)). The increase in [GSH] by
      bpV(phen) was partly inhibited by buthionine sulphoximine (BSO; 50 micromol l(
      1)), a blocker of GSH synthesis, and by 1,3-bis-(2-chloroethyl)-1-nitrosourea
      (BCNU; 100 micromol l(-1)), an inhibitor of glutathione disulphide reductase. By
      comparison, the effect of pyruvate was not altered by BSO but was completely
      blocked by BCNU. Studies using inhibitors of signalling cascades indicated that
      upregulation of [GSH] by bpV(phen) in myocytes from post-MI hearts was mediated
      by mitogen activated protein kinase/extracellular signal-regulated kinase kinase
      1/2 and p38 mitogen-activated protein kinase but not by phosphatidylinositol 3
      kinase. The effect of pyruvate was not altered by any kinase inhibitor tested. In
      cells loaded with the probe TEMPO-9-AC to monitor superoxide anion, baseline
      fluorescence was 2.3-fold greater in post-MI myocytes than in sham control
      myocytes (P < 0.05) and was markedly decreased by diphenyleneiodonium (30
      micromol l(-1)), an inhibitor of NADPH oxidase, exogenous GSH (10 mmol l(-1)) or
      bpV(phen). In parallel studies, [GSH] in post-MI myocytes was also normalized by
      diphenyleneiodonium or exogenous GSH. These data show that GSH is differentially
      regulated by receptor tyrosine kinase-dependent and -independent agonists that
      maintain functional GSH levels necessary to neutralize excess generation of
      reactive oxygen species in the failing heart.

PMID- 19395661
TI  - Effects of 17beta-oestradiol on rat detrusor smooth muscle contractility.
AB  - The aim of this study was to investigate the effect of 17beta-oestradiol (E(2))
      on detrusor smooth muscle contractility and its possible neuroprotective role
      against ischaemic-like condition, which could arise during overactive bladder
      disease. The effect of E(2) was investigated on rat detrusor muscle strips
      stimulated with carbachol, KCl and electrically, in the absence or presence of a
      selective oestrogen receptor antagonist (ICI 182,780) and, by using confocal
      Ca(2+) imaging technique, measuring the amplitude (DeltaF/F(0)) and the frequency
      of spontaneous whole cell Ca(2+) flashes. Moreover, the effect of 1 and 2 h of
      anoxia-glucopenia and reperfusion (A-G/R), in the absence or presence of the
      hormone, was evaluated in rat detrusor strips perfused with Krebs solution which
      underwent electrical field stimulation to stimulate intrinsic nerves; the
      amplitude and the frequency of Ca(2+) flashes were also measured. 17beta
      Oestradiol exhibited antispasmogenic activity assessed on detrusor strips
      depolarized with 60 mm KCl at two different Ca(2+) concentrations. 17beta
      Oestradiol at the highest concentration tested (30 microm) significantly
      decreased detrusor contractions induced by all the stimuli applied. In addition,
      the amplitude and the frequency of spontaneous Ca(2+) flashes were significantly
      decreased in the presence of E(2) (10 and 30 microm) compared with control
      detrusor strips. In strips subjected to A-G/R, a significant increase in the
      amplitude of both spontaneous and evoked flashes was observed. 17beta-Oestradiol
      was found to increase the recovery of detrusor strips subjected to A-G/R. The
      ability of E(2) to suppress contraction in control conditions may explain its
      ability to aid recovery following A-G/R.

PMID- 19395663
TI  - Identification of the Candida albicans Cap1p regulon.
AB  - Cap1p, a transcription factor of the basic region leucine zipper family,
      regulates the oxidative stress response (OSR) in Candida albicans. Alteration of
      its C-terminal cysteine-rich domain (CRD) results in Cap1p nuclear retention and
      transcriptional activation. To better understand the function of Cap1p in C.
      albicans, we used genome-wide location profiling (chromatin immunoprecipitation
      on-chip) to identify its transcriptional targets in vivo. A triple-hemagglutinin
      (HA(3)) epitope was introduced at the C terminus of wild-type Cap1p (Cap1p-HA(3))
      or hyperactive Cap1p with an altered CRD (Cap1p-CSE-HA(3)). Location profiling
      using whole-genome oligonucleotide tiling microarrays identified 89 targets bound
      by Cap1p-HA(3) or Cap1p-CSE-HA(3) (the binding ratio was at least twofold; P < or
      = 0.01). Strikingly, Cap1p binding was detected not only at the promoter region
      of its target genes but also at their 3' ends and within their open reading
      frames, suggesting that Cap1p may associate with the transcriptional or chromatin
      remodeling machinery to exert its activity. Overrepresented functional groups of
      the Cap1p targets (P < or = 0.02) included 11 genes involved in the OSR (CAP1,
      GLR1, TRX1, SOD1, CAT1, and others), 13 genes involved in response to drugs
      (PDR16, MDR1, FLU1, YCF1, FCR1, and others), 4 genes involved in phospholipid
      transport (PDR16, GIT1, RTA2, and orf19.932), and 3 genes involved in the
      regulation of nitrogen utilization (GST3, orf19.2693, and orf19.3121), suggesting
      that Cap1p has other cellular functions in addition to the OSR. Bioinformatic
      analyses of the bound sequences suggest that Cap1p recognizes the DNA motif 5'
      MTKASTMA. Finally, transcriptome analyses showed that increased expression
      generally accompanies Cap1p binding at its targets, indicating that Cap1p
      functions as a transcriptional activator.

PMID- 19395664
TI  - Comparative genomics using microarrays reveals divergence and loss of virulence
      associated genes in host-specific strains of the insect pathogen Metarhizium
      anisopliae.
AB  - Many strains of Metarhizium anisopliae have broad host ranges, but others are
      specialists and adapted to particular hosts. Patterns of gene duplication,
      divergence, and deletion in three generalist and three specialist strains were
      investigated by heterologous hybridization of genomic DNA to genes from the
      generalist strain Ma2575. As expected, major life processes are highly conserved,
      presumably due to purifying selection. However, up to 7% of Ma2575 genes were
      highly divergent or absent in specialist strains. Many of these sequences are
      conserved in other fungal species, suggesting that there has been rapid evolution
      and loss in specialist Metarhizium genomes. Some poorly hybridizing genes in
      specialists were functionally coordinated, indicative of reductive evolution.
      These included several involved in toxin biosynthesis and sugar metabolism in
      root exudates, suggesting that specialists are losing genes required to live in
      alternative hosts or as saprophytes. Several components of mobile genetic
      elements were also highly divergent or lost in specialists. Exceptionally, the
      genome of the specialist cricket pathogen Ma443 contained extra insertion
      elements that might play a role in generating evolutionary novelty. This study
      throws light on the abundance of orphans in genomes, as 15% of orphan sequences
      were found to be rapidly evolving in the Ma2575 lineage.

PMID- 19395665
TI  - Intranasal organic dust exposure-induced airway adaptation response marked by
      persistent lung inflammation and pathology in mice.
AB  - Organic dust exposure in agricultural environments results in an inflammatory
      response that attenuates over time, but repetitive exposures can result in
      chronic respiratory disease. Animal models to study these mechanisms are limited.
      This study investigated the effects of single vs. repetitive dust-induced airway
      inflammation in mice by intranasal exposure method. Mice were exposed to swine
      facility dust extract (DE) or saline once and once daily for 1 and 2 wk. Dust
      exposure resulted in increased bronchoalveolar lavage fluid neutrophils and
      macrophages after single and repetitive exposures. Lavage fluid TNFalpha, IL-6,
      keratinocyte chemoattractant, and macrophage inflammatory protein-2 were
      significantly increased after single and repetitive dust exposures, but were
      dampened in 2-wk dust-exposed mice compared with single exposure. Dust exposure
      induced PKCalpha and -epsilon activation in isolated tracheal epithelial cells
      but were dampened with repetitive exposures. Ex vivo stimulation of alveolar
      macrophages from 2-wk animals demonstrated reduced cytokine responsiveness and
      phagocytic ability. Significant lung pathology occurred with development of mixed
      mononuclear cellular aggregates (T and B lymphocytes, phagocytes) after
      repetitive dust exposure, a novel observation. Airway hyperresponsiveness to
      methacholine occurred after single dust exposure but resolved after 2 wk.
      Collectively, intranasal exposure to DE results in significant lung inflammatory
      and pathological responses marked by a modulated innate immune response to single
      and repetitive dust exposures that is associated with PKC activity.

PMID- 19395666
TI  - Soluble adenylyl cyclase-dependent microtubule disassembly reveals a novel
      mechanism of endothelial cell retraction.
AB  - Soluble adenylyl cyclase toxins, such as Pseudomonas aeruginosa exoY, generate a
      cAMP pool that retracts cell borders. However, the cytoskeletal basis by which
      this cAMP signal retracts cell borders is not known. We sought to determine
      whether activation of chimeric, soluble adenylyl cyclase I/II (sACI/II)
      reorganizes either microtubules or peripheral actin. Endothelial cells were
      stably transfected with either green fluorescent protein-labeled alpha-tubulin or
      beta-actin, and then infected with adenovirus to express sACI/II. Forskolin,
      which stimulates both the endogenously expressed transmembrane adenylyl cyclases
      and sACI/II, induced cell retraction accompanied by the reorganization of
      peripheral microtubules. However, cortical filamentous-actin (f-actin) did not
      reorganize into stress fibers, and myosin light-chain-20 phosphorylation was
      decreased. Isoproterenol, which activates endogenous adenylyl cyclases but does
      not activate sACI/II, did not induce endothelial cell gaps and did not influence
      microtubule or f-actin architecture. Thus, sACI/II generates a cAMP signal that
      reorganizes microtubules and induces cell retraction, without inducing f-actin
      stress fibers. These findings illustrate that endothelial cell gap formation can
      proceed without f-actin stress fiber formation, and provide mechanistic insight
      how bacterial adenylyl cyclase toxins reorganize the cytoskeleton to induce cell
      rounding.

PMID- 19395667
TI  - Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and
      atherogenesis.
AB  - More than 100 million people in the United States live in areas that exceed
      current ozone air quality standards. In addition to its known pulmonary effects,
      environmental ozone exposures have been associated with increased hospital
      admissions related to cardiovascular events, but to date, no studies have
      elucidated the potential molecular mechanisms that may account for exposure
      related vascular impacts. Because of the known pulmonary redox and immune biology
      stemming from ozone exposure, we hypothesized that ozone inhalation would
      initiate oxidant stress, mitochondrial damage, and dysfunction within the
      vasculature. Accordingly, these factors were quantified in mice consequent to a
      cyclic, intermittent pattern of ozone or filtered air control exposure. Ozone
      significantly modulated vascular tone regulation and increased oxidant stress and
      mitochondrial DNA damage (mtDNA), which was accompanied by significantly
      decreased vascular endothelial nitric oxide synthase protein and indices of
      nitric oxide production. To examine influences on atherosclerotic lesion
      formation, apoE-/- mice were exposed as above, and aortic plaques were
      quantified. Exposure resulted in significantly increased atherogenesis compared
      with filtered air controls. Vascular mitochondrial damage was additionally
      quantified in ozone- and filtered air-exposed infant macaque monkeys. These
      studies revealed that ozone increased vascular mtDNA damage in nonhuman primates
      in a fashion consistent with known atherosclerotic lesion susceptibility in
      humans. Consequently, inhaled ozone, in the absence of other environmental
      toxicants, promotes increased vascular dysfunction, oxidative stress,
      mitochondrial damage, and atherogenesis.

PMID- 19395668
TI  - Knockdown of stromal interaction molecule 1 attenuates store-operated Ca2+ entry
      and Ca2+ responses to acute hypoxia in pulmonary arterial smooth muscle.
AB  - Stromal interaction molecule 1 (STIM1) is a recently discovered membrane-spanning
      protein thought to sense lumenal Ca(2+) in sarco(endo)plasmic reticulum (SR/ER)
      and transduce activation of Ca(2+)-permeable store-operated channels (SOC) in
      plasmalemma in response to SR/ER Ca(2+) depletion. To evaluate the role of STIM1
      and a closely related protein, STIM2, in Ca(2+) signaling of rat distal pulmonary
      arterial smooth muscle cells (PASMC) during hypoxia, we used fluorescent
      microscopy and the Ca(2+)-sensitive dye, fura 2, to measure basal intracellular
      Ca(2+) concentration ([Ca(2+)](i)), store-operated Ca(2+) entry (SOCE), and
      increases in [Ca(2+)](i) caused by acute hypoxia (4% O(2)) or depolarization (60
      mmol/l KCl) in cells treated with small interfering RNA targeted to STIM1
      (siSTIM1) or STIM2 (siSTIM2). As determined by real-time quantitative PCR
      analysis (qPCR), STIM1 mRNA was 200-fold more abundant than STIM2 in untreated
      control PASMC. siSTIM1 and siSTIM2 caused specific and significant knockdown of
      both mRNA measured by qPCR and protein measured by Western blotting. siSTIM1
      markedly inhibited SOCE and abolished the sustained [Ca(2+)](i) response to
      hypoxia but did not alter the initial transient [Ca(2+)](i) response to hypoxia,
      the [Ca(2+)](i) response to depolarization, or basal [Ca(2+)](i). The only effect
      of siSTIM2 was a smaller inhibition of SOCE. We conclude that STIM1 was
      quantitatively more important than STIM2 in activation of SOC in rat distal PASMC
      and that the increase in [Ca(2+)](i) induced by acute hypoxia in these cells
      required SR Ca(2+) release and STIM1-dependent activation of SOC.

PMID- 19395669
TI  - Neutral sphingomyelinase 2 is activated by cigarette smoke to augment ceramide
      induced apoptosis in lung cell death.
AB  - Cigarette smoke (CS) induces a rapid, sustained upregulation of ceramide
      production in human bronchial epithelial cells, leading to increased apoptosis.
      Using loss-of-function and overexpression analyses, we show that neutral
      sphingomyelinase 2 (nSMase2) is required for CS-mediated ceramide generation and
      apoptosis. Glutathione (GSH), a crucial antioxidant in lung defense, blocks
      nSMase2 activity and thus inhibits apoptosis triggered by CS. We found that the
      exposure to CS, as with exposure to H(2)O(2), results in increased nSMase2
      activation leading to ceramide generation and therefore increased apoptosis.
      Interestingly, exposure of cells to GSH abolishes nSMase2 activation caused by CS
      and leads to a decrease in CS-induced apoptosis. This suggests that the effects
      of CS oxidants on nSMase2 are counteracted by GSH. Our data support a model where
      CS induces nSMase2 activation thereby increasing membrane-sphingomyelin
      hydrolysis to ceramide. In turn, elevated ceramide enhances airway epithelial
      cell death, which causes bronchial and alveolar destruction and lung injury in
      pulmonary diseases.

PMID- 19395670
TI  - Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca2+
      reuptake in human airway smooth muscle.
AB  - Airway inflammation leads to increased intracellular Ca(2+) ([Ca(2+)](i)) levels
      in airway smooth muscle (ASM) cells. Sarcoplasmic reticulum Ca(2+) release and
      reuptake are key components of ASM [Ca(2+)](i) regulation. Ca(2+) reuptake occurs
      via sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) and is regulated by the
      inhibitory protein phospholamban (PLB) in many cell types. In human ASM, we
      tested the hypothesis that inflammation increases PLB, thus inhibiting SERCA
      function, and leading to maintained [Ca(2+)](i) levels. Surprisingly, we found
      that human ASM does not express PLB protein (although mRNA is detectable).
      Overnight exposure to the proinflammatory cytokines TNFalpha and IL-13 did not
      induce PLB expression, raising the issue of how SERCA is regulated. We then found
      that direct SERCA phosphorylation (via CaMKII) occurs in human ASM. In fura-2
      loaded human ASM cells, we found that the CaMKII antagonist KN-93 significantly
      slowed the rate of fall of [Ca(2+)](i) transients induced by ACh or bradykinin
      (in zero extracellular Ca(2+)), suggesting a role for CaMKII-mediated SERCA
      regulation. SERCA expression was decreased by cytokine exposure, and the rate of
      fall of [Ca(2+)](i) transients was slowed in cells exposed to TNFalpha and IL-13.
      Cytokine effects on Ca(2+) reuptake were unaffected by additional exposure to KN
      93. These data indicate that in human ASM, SERCA is regulated by mechanisms such
      as CaMKII and that airway inflammation maintains [Ca(2+)](i) levels by decreasing
      SERCA expression and slowing Ca(2+) reuptake.

PMID- 19395671
TI  - Stimulation of the lateral geniculate, superior colliculus, or visual cortex is
      sufficient for eyeblink conditioning in rats.
AB  - The role of the cerebellum in eyeblink conditioning is well established. Less
      work has been done to identify the necessary conditioned stimulus (CS) pathways
      that project sensory information to the cerebellum. A possible visual CS pathway
      has been hypothesized that consists of parallel inputs to the pontine nuclei from
      the lateral geniculate nucleus (LGN), superior colliculus (SC), pretectal nuclei,
      and visual cortex (VCTX) as reported by Koutalidis and colleagues in an earlier
      paper. The following experiments examined whether electrical stimulation of
      neural structures in the putative visual CS pathway can serve as a sufficient CS
      for eyeblink conditioning in rats. Unilateral stimulation of the ventral LGN
      (Experiment 1), SC (Experiment 2), or VCTX (Experiment 3) was used as a CS paired
      with a periorbital shock unconditioned stimulus. Stimulation was delivered to the
      hemisphere contralateral to the conditioned eye. Rats in all experiments were
      given five 100-trial sessions of paired or unpaired eyeblink conditioning with
      the stimulation CS followed by three paired sessions with a light CS. Stimulation
      of each visual area when paired with the unconditioned stimulus supported
      acquisition of eyeblink conditioned responses (CRs) and substantial savings when
      switched to a light CS. The results provide evidence for a unilateral parallel
      visual CS pathway for eyeblink conditioning that includes the LGN, SC, and VCTX
      inputs to the pontine nuclei.

PMID- 19395672
TI  - Endobrevin/VAMP-8-dependent dense granule release mediates thrombus formation in
      vivo.
AB  - Individuals whose platelets lack dense or alpha-granules suffer various degrees
      of abnormal bleeding, implying that granule cargo contributes to hemostasis.
      Despite these clinical observations, little is known regarding the effects of
      impaired platelet granule secretion on thrombus formation in vivo. In platelets,
      SNARE proteins mediate the membrane fusion events required for granule cargo
      release. Endobrevin/VAMP-8 is the primary vesicle-SNARE (v-SNARE) responsible for
      efficient release of dense and alpha-granule contents; thus, VAMP-8(-/-) mice are
      a useful model to evaluate the importance of platelet granule secretion in
      thrombus formation. Thrombus formation, after laser-induced vascular injury, in
      these mice is delayed and decreased, but not absent. In contrast, thrombus
      formation is almost completely abolished in the mouse model of Hermansky-Pudlak
      syndrome, ruby-eye, which lacks dense granules. Evaluation of aggregation of VAMP
      8(-/-) and ruby-eye platelets indicates that defective ADP release is the primary
      abnormality leading to impaired aggregation. These results demonstrate the
      importance of dense granule release even in the earliest phases of thrombus
      formation and validate the distal platelet secretory machinery as a potential
      target for antiplatelet therapies.

PMID- 19395673
TI  - Vdelta1 T lymphocytes producing IFN-gamma and IL-17 are expanded in HIV-1
      infected patients and respond to Candida albicans.
AB  - In early HIV-1 infection, Vdelta1 T lymphocytes are increased in peripheral blood
      and this is related to chemokine receptor expression, chemokine response, and
      recirculation. Herein we show that, at variance with healthy donors, in HIV-1
      infected patients ex vivo-isolated Vdelta1 T cells display cytoplasmic interferon
      gamma (IFN-gamma). Interestingly, these cells coexpress cytoplasmic interleukin
      17 (IL-17), and bear the CD27 surface marker of the memory T-cell subset. Vdelta1
      T cells, isolated from either patients or healthy donors, can proliferate and
      produce IFN-gamma and IL-17 in response to Candida albicans in vitro, whereas
      Vdelta2 T cells respond with proliferation and IFN-gamma/IL-17 production to
      mycobacterial or phosphate antigens. These IFN-gamma/IL-17 double-producer
      gammadelta T cells express the Th17 RORC and the Th1 TXB21 transcription factors
      and bear the CCR7 homing receptor and the CD161 molecule that are involved in
      gammadelta T-cell transendothelial migration. Moreover, Vdelta1 T cells
      responding to C albicans express the chemokine receptors CCR4 and CCR6. This
      specifically equipped circulating memory gammadelta T-cell population might play
      an important role in the control of HIV-1 spreading and in the defense against
      opportunistic infections, possibly contributing to compensate for the impairment
      of CD4(+) T cells.

PMID- 19395676
TI  - Sulfated polysaccharides from marine sponges (Porifera): an ancestor cell-cell
      adhesion event based on the carbohydrate-carbohydrate interaction.
AB  - Marine sponges (Porifera) are ancient and simple eumetazoans. They constitute key
      organisms in the evolution from unicellular to multicellular animals. We now
      demonstrated that pure sulfated polysaccharides from marine sponges are
      responsible for the species-specific cell-cell interaction in these
      invertebrates. This conclusion was based on the following observations: (1) each
      species of marine sponge has a single population of sulfated polysaccharide,
      which differ among the species in their sugar composition and sulfate content;
      (2) sulfated polysaccharides from sponge interact with each other in a species
      specific way, as indicated by an affinity chromatography assay, and this
      interaction requires calcium; (3) homologous, but not heterologous, sulfated
      polysaccharide inhibits aggregation of dissociated sponge cells; (4) we also
      observed a parallel between synthesis of the sulfated polysaccharide and
      formation of large aggregates of sponge cells, known as primmorphs. Once
      aggregation reached a plateau, the demand for the de novo synthesis of sulfated
      polysaccharides ceased. Heparin can mimic the homologous sulfated polysaccharide
      on the in vitro interaction and also as an inhibitor of aggregation of the
      dissociated sponge cells. However, this observation is not relevant for the
      biology of the sponge since heparin is not found in the invertebrate. In
      conclusion, marine sponges display an ancestor event of cell-cell adhesion, based
      on the calcium-dependent carbohydrate-carbohydrate interaction.

PMID- 19395675
TI  - PAF-acetylhydrolase expressed during megakaryocyte differentiation inactivates
      PAF-like lipids.
AB  - Platelet activating factor (PAF) and PAF-like lipids induce inflammatory
      responses in target cells. These lipid mediators are inactivated by PAF
      acetylhydrolase (PAF-AH). The PAF signaling system affects the growth of
      hematopoietic CD34(+) cells, but roles for PAF-AH in this process are unknown.
      Here, we investigated PAF-AH function during megakaryopoiesis and found that
      human CD34(+) cells accumulate this enzymatic activity as they differentiate
      toward megakaryocytes, consistent with the expression of mRNA and protein for the
      plasma PAF-AH isoform. Inhibition of endogenous PAF-AH activity in differentiated
      megakaryocytes increased formation of lipid mediators that signaled the PAF
      receptor (PAFR) in fully differentiated human cells such as neutrophils, as well
      as megakaryocytes themselves. PAF-AH also controlled megakaryocyte
      alpha(IIb)beta(3)-dependent adhesion, cell spreading, and mobility that relied on
      signaling through the PAFR. Together these data suggest that megakaryocytes
      generate PAF-AH to modulate the accumulation of intracellular phospholipid
      mediators that may detrimentally affect megakaryocyte development and function.

PMID- 19395674
TI  - The ITP syndrome: pathogenic and clinical diversity.
AB  - Immune thrombocytopenia (ITP) is mediated by platelet autoantibodies that
      accelerate platelet destruction and inhibit their production. Most cases are
      considered idiopathic, whereas others are secondary to coexisting conditions.
      Insights from secondary forms suggest that the proclivity to develop platelet
      reactive antibodies arises through diverse mechanisms. Variability in natural
      history and response to therapy suggests that primary ITP is also heterogeneous.
      Certain cases may be secondary to persistent, sometimes inapparent, infections,
      accompanied by coexisting antibodies that influence outcome. Alternatively,
      underlying immune deficiencies may emerge. In addition, environmental and genetic
      factors may impact platelet turnover, propensity to bleed, and response to ITP
      directed therapy. We review the pathophysiology of several common secondary forms
      of ITP. We suggest that primary ITP is also best thought of as an autoimmune
      syndrome. Better understanding of pathogenesis and tolerance checkpoint defects
      leading to autoantibody formation may facilitate patient-specific approaches to
      diagnosis and management.

PMID- 19395677
TI  - Genetic analysis of glucosidase II beta-subunit in trimming of high-mannose-type
      glycans.
AB  - Glucosidase II (G-II) is a glycoprotein-processing enzyme that successively
      cleaves two alpha1,3-linked glucose residues from N-linked oligosaccharides in
      the endoplasmic reticulum. G-II is a heterodimer whose alpha-subunit contains a
      glycosidase active site, but the function(s) of the beta-subunit remain poorly
      defined. We report here an in vivo enzymatic analysis using gene disruptants
      lacking either the G-II alpha- or beta-subunit in the filamentous fungus
      Aspergillus oryzae. Using synthetic oligosaccharides as probes, G-II activity of
      the membranous fraction of the gene disruptants was investigated. The fraction
      lacking the beta-subunit retained hydrolytic activity toward p-nitrophenyl alpha
      D-glucopyranoside but was inactive toward both Glc(2)Man(9)GlcNAc(2) and
      Glc(1)Man(9)GlcNAc(2). When the fraction containing the beta-subunit was added to
      the one including the alpha-subunit, the glucosidase activity was restored. These
      results suggested that the beta-subunit confers the substrate specificity toward
      di- and monoglucosylated glycans on the glucose-trimming activity of the alpha
      subunit.

PMID- 19395678
TI  - Rapamycin-insensitive up-regulation of MMP2 and other genes in tuberous sclerosis
      complex 2-deficient lymphangioleiomyomatosis-like cells.
AB  - Increased matrix metalloproteinase (MMP) activity has been implicated in the
      pathogenesis of lymphangioleiomyomatosis (LAM). The objective of this study was
      to investigate how tuberous sclerosis complex (TSC) 1 or TSC2 deficiency alters
      MMP expression and regulation. We studied immortalized cells that lack TSC2
      derived from an angiomyolipoma of a patient with LAM, a TSC2 addback derivative,
      and murine embryonic fibroblast cells that lack Tsc1 or -2 and respective
      controls. Global gene expression analysis was performed in the angiomyolipoma and
      derivative cell lines. MMP levels in the conditioned media from these cells were
      analyzed by zymography and ELISA. We found increased MMP-2 expression in cells
      lacking TSC1/TSC2 compared with their respective controls by zymography. MMP-2
      overproduction by these cells was not affected by rapamycin treatment. Gene
      expression analysis confirmed increased MMP-2 gene expression that was not
      affected by rapamycin. Furthermore, multiple other genes were found to be
      overexpressed in rapamycin-treated TSC2-deficient cells compared with TSC2(+)
      cells. We conclude that TSC1/TSC2 deficiency leads to MMP-2 overproduction that
      is rapamycin-insensitive, and that several genes exhibit similar patterns,
      suggesting that TSC1/TSC2-dependent, but mammalian target of rapamycin
      independent, pathways may be involved in the pathogenesis of LAM.

PMID- 19395679
TI  - Nkx2.5/Csx represses myofibroblast differentiation.
AB  - Myofibroblasts are known to play key roles in wound healing and fibrosis. They
      are thought to arise de novo from fibroblasts, and are characterized by induction
      of alpha-smooth muscle actin (alpha-SMA) expression. The homeobox transcription
      factor Csx/Nkx2.5 is critical in heart development and cardiogenesis by inducing
      expression of genes associated with cardiomyocyte differentiation. Here, we
      report a novel repressor activity of Nkx2.5 on myofibroblast differentiation.
      Because a key marker of myofibroblast differentiation is expression of the alpha
      SMA gene, we first scanned its promoter region for possible cis-acting elements.
      The results show three potential binding sites (designated Nkx2.5 element [NKE]
      1, -2, and -3) containing the Nkx2.5/Csx consensus binding motif (5'-TNNAGTG-3').
      To determine their functional importance, site-directed mutagenesis directed at
      these elements individually and in combination indicated that mutation of NKE1
      and -3 significantly enhanced alpha-SMA gene promoter activity, whereas mutation
      of NKE2 did not have a significant effect. The results of gel shift assays
      confirmed that Nkx2.5 could bind to both NKE1 and -3, but not to NKE2. Consistent
      with the mutagenesis studies, ectopically induced expression of Nkx2.5 inhibited
      alpha-SMA gene expression. Analysis of nkx2.5 gene expression indicates that it
      was significantly induced by basic fibroblast growth factor treatment of isolated
      lung fibroblasts in vitro. In vivo, lung Nkx2.5 expression was significantly
      diminished in bleomycin-induced pulmonary fibrosis. These findings are consistent
      with a novel function for Nkx2.5 as a repressor of alpha-SMA gene transcription,
      which may be of homeostatic significance as a means of suppressing myofibroblast
      differentiation in the absence of tissue injury.

PMID- 19395680
TI  - Mixed S-nitrosylated polymerized bovine hemoglobin species moderate hemodynamic
      effects in acutely hypoxic rats.
AB  - Hemoglobin (Hb)-based oxygen carriers (HBOCs) are being developed as a potential
      therapy for increasing tissue oxygenation, yet they have not reached their full
      potential because of unwanted hemodynamic side effects (vasoconstriction, low
      cardiac output, and oxygen delivery) due in part to nitric oxide (NO) scavenging
      by cell-free Hb. It may be possible to overcome the NO scavenging effect by
      coinfusing S-nitrosylated (SNO) HBOC along with unmodified HBOC. SNO-HBOC, like
      free Hb, may act as an NO donor in low-oxygen conditions. We hypothesized that an
      unaltered HBOC, polymerized bovine Hb (PBvHb), coinfused with an SNO-PBvHb, would
      improve hemodynamics and oxygen delivery during hypoxia. Vascular oxygen content
      and hemodynamics were determined after euvolemic rats were infused (3 ml) with
      lactated Ringer's solution, PBvHb, SNO-PBvHb, or PBvHb plus SNO-PBvHb (1:10)
      during normoxia or acute hypoxia (fraction of inspired oxygen = 10%, 120 min).
      Hemodynamic side effects resulting from PBvHb infusion (vasoconstriction,
      elevated pulmonary blood pressure, and reduced cardiac output) were offset by SNO
      PBvHb in acute hypoxic, but not normoxic, conditions. These data support the
      potential use of HBOC mixed with SNO-HBOC for the treatment of conditions in
      which acute hypoxia is present, such as tumor oxygenation, wound healing,
      hemorrhagic trauma, and sickle cell and hemolytic anemia.

PMID- 19395681
TI  - Guidelines for quantitative rt-PCR.

PMID- 19395682
TI  - Real-time quantitative RT-PCR: design, calculations, and statistics.

PMID- 19395683
TI  - The MYB23 gene provides a positive feedback loop for cell fate specification in
      the Arabidopsis root epidermis.
AB  - The specification of cell fates during development requires precise regulatory
      mechanisms to ensure robust cell type patterns. Theoretical models of pattern
      formation suggest that a combination of negative and positive feedback mechanisms
      are necessary for efficient specification of distinct fates in a field of
      differentiating cells. Here, we examine the role of the R2R3-MYB transcription
      factor gene, AtMYB23 (MYB23), in the establishment of the root epidermal cell
      type pattern in Arabidopsis thaliana. MYB23 is closely related to, and is
      positively regulated by, the WEREWOLF (WER) MYB gene during root epidermis
      development. Furthermore, MYB23 is able to substitute for the function of WER and
      to induce its own expression when controlled by WER regulatory sequences. We also
      show that the MYB23 protein binds to its own promoter, suggesting a MYB23
      positive feedback loop. The localization of MYB23 transcripts and MYB23-green
      fluorescent protein (GFP) fusion protein, as well as the effect of a chimeric
      MYB23-SRDX repressor construct, links MYB23 function to the developing non-hair
      cell type. Using mutational analyses, we find that MYB23 is necessary for precise
      establishment of the root epidermal pattern, particularly under conditions that
      compromise the cell specification process. These results suggest that MYB23
      participates in a positive feedback loop to reinforce cell fate decisions and
      ensure robust establishment of the cell type pattern in the Arabidopsis root
      epidermis.

PMID- 19395684
TI  - Illicit drug use as a predictor of smoking cessation treatment outcome.
AB  - INTRODUCTION: Evidence from cross-sectional survey data suggests a negative
      association between illicit drug use and smoking cessation. In a prospective
      clinical cohort, we examined whether illicit drug users were less successful than
      other smokers when making an attempt to stop smoking. METHODS: A total of 100
      smokers attending a tobacco dependence clinic were studied. Pretreatment
      questionnaire measures of illicit drug use, demographics, health history, and
      tobacco smoking were taken. Treatment consisted of seven weekly behavioral
      support sessions plus nicotine replacement therapy or bupropion. Short-term
      outcome was assessed at the end of the treatment by self-report and carbon
      monoxide (CO) verification. RESULTS: A total of 24 smokers (24%) had used illicit
      drugs during the previous 30 days. Drug users were less likely to stop smoking
      than were nonusers. The difference in CO-verified success rates was 26.1% (29.2%
      vs. 55.3%, 95% CI = 4.8%-47.4%), and the odds ratio was 0.33 (95% CI = 0.12
      0.89). Adjustment for group differences on all the measured background and
      treatment characteristics affected this result only marginally. DISCUSSION:
      Illicit drug use appears to have a significant detrimental effect on the success
      of an attempt to stop smoking. This effect is not explained by differences
      between drug users and nonusers on established prognostic factors. These first
      results in a prospective sample support findings from a large U.S. population
      survey of smoking cessation rates in drug users and nonusers. If these results
      are corroborated, clinicians treating smokers should consider developing new
      protocols to improve outcomes in smokers using illicit drugs.

PMID- 19395685
TI  - Evaluation of the accuracy of self-reported smoking in pregnancy when the
      biomarker level in an active smoker is uncertain.
AB  - INTRODUCTION: Our main objective was to estimate smoking prevalence as well as
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) of self-reported smoking among pregnant women in Edmonton,
      Canada, at 15-16 weeks of gestation. METHODS: We used serum samples to assemble a
      cohort of pregnant women who underwent an optional second-trimester screening for
      chromosomal and developmental anomalies. We determined cotinine concentrations
      for 92 self-reported smokers (11% of the cohort) and for 285 self-reported
      nonsmoking mothers, using adapted urinary cotinine assay. Self-reports were
      collected at the time of delivery. In a validation study, serum cotinine was
      determined for known smokers and nonsmokers and used, within a Bayesian
      statistical framework, to define the distribution of cutoffs that differentiate
      true smokers from nonsmokers. This distribution of cutoffs was used to construct
      multiple two-by-two tables to obtain the distribution of sensitivity,
      specificity, PPV, NPV, and prevalence. RESULTS: Sensitivity was poor (M = 47.4%,
      SD = 17.3%), but specificity was nearly perfect (M = 94.9%, SD = 1.1%). PPV (M =
      66.6%, SD = 11.7%) was smaller than NPV (M = 84.7%, SD = 14.3%). In our sample,
      the prevalence of true smoking at 15-16 weeks of gestation was described by a
      skewed distribution with a mean of 21.6% (SD = 13.8%) and a median of 16.6%.
      DISCUSSION: The strength of the present study includes blinding of subjects to
      the intention to test their sera for a biomarker of smoking. A limitation was the
      use of a nonrandom sample restricted to pregnancies that resulted in live births.
      We discuss data collection methods that would elicit more accurate smoking
      histories from pregnant women.

PMID- 19395686
TI  - Smokeless tobacco cessation in military personnel: a randomized controlled trial.
AB  - INTRODUCTION: Military personnel are twice as likely as civilians to use
      smokeless tobacco (ST). This study evaluated the efficacy of a minimal-contact ST
      cessation program in military personnel. METHODS: Participants were recruited
      from 24 military dental clinics across the United States during annual dental
      examinations. Participants were 785 active-duty military personnel who were
      randomly assigned to receive a minimal-contact behavioral treatment (n = 392) or
      usual care (n = 393). The behavioral treatment included an ST cessation manual, a
      videotape cessation guide tailored for military personnel, and three 15-min
      telephone counseling sessions using motivational interviewing methods. Usual care
      consisted of standard procedures that are part of the annual dental examination,
      including recommendations to quit using ST and referral to extant local tobacco
      cessation programs. Participants were assessed at 3 and 6 months after
      enrollment. RESULTS: Participants in the ST cessation program were significantly
      more likely to be abstinent from all tobacco, as assessed by repeated point
      prevalence at both 3 and 6 months (25.0%), and were significantly more likely to
      be abstinent from ST use for 6 months, as assessed by prolonged abstinence
      (16.8%), compared with participants in usual care (7.6% and 6.4%, respectively).
      DISCUSSION: These results indicate that a minimal-contact behavioral treatment
      can significantly reduce ST use in military personnel and has the potential for
      widespread dissemination. If ST users were identified in dental visits and
      routinely referred to telephone counseling, this could have a substantial benefit
      for the health and well-being of military personnel.

PMID- 19395687
TI  - Association of cotinine levels and preeclampsia among African-American women.
AB  - INTRODUCTION: Although prior studies have shown that smoking reduces preeclampsia
      risk, the relationship between nicotine level and preeclampsia risk is not known.
      Our objective was to study the effects of smoking on the incidence of
      preeclampsia in African-American women using cotinine, a quantitative marker of
      nicotine. METHODS: We performed a secondary analysis of data collected
      prospectively in Project District of Columbia Healthy Outcomes of Pregnancy
      Education. Our study included 724 African-American women. Self-reported smoking,
      cotinine levels, and pregnancy outcomes were examined. RESULTS: Some 18% of
      participants were smokers. Women with salivary cotinine levels greater than 200
      ng/ml had infants with lower birth weights and a higher incidence of small-for
      gestational-age infants than women with cotinine levels of 200 ng/ml or less.
      Exact logistic regression analysis revealed that women with salivary cotinine
      levels greater than 200 ng/ml had a significantly lower incidence of
      preeclampsia, compared with women with cotinine levels of 200 ng/ml or less, in
      unadjusted analysis (odds ratio [OR] = 0.16, 95% CI = 0-0.90). After controlling
      for age, parity, and medical comorbidities, the trend was observed, but the
      effect was no longer significant (adjusted odds ratio [AOR] = 0.19, 95% CI = 0
      1.11). We found no significant differences in preeclampsia rates using lower
      cutoffs of cotinine exposure. We did not observe a decrease in preeclampsia
      incidence at low or moderate cotinine levels. DISCUSSION: Women with the highest
      cotinine levels may have a decreased risk for preeclampsia, although this effect
      was not significant after controlling for other risk factors.

PMID- 19395688
TI  - Sustained-release bupropion for hospital-based smoking cessation: a randomized
      trial.
AB  - INTRODUCTION: Bupropion is a first-line pharmacological aid for smoking
      cessation; however, no clinical trials have been conducted in a general
      population of hospitalized smokers. METHODS: We enrolled 85 smokers in a hospital
      based randomized smoking cessation trial conducted at the San Francisco Veterans
      Affairs Medical Center. A total of 42 participants received a 7-week course of
      sustained-release bupropion and 43 participants received placebo. All
      participants received cognitive-behavioral counseling. We screened 14,997
      patients, of whom 25% were current smokers. Of the 536 smokers who met the entry
      criteria, 451 opted not to enroll. We determined on-medication, end-of
      medication, 3-month, and 6-month smoking cessation rates. RESULTS: At the end of
      7 weeks of drug treatment, self-reported quit rates were equivalent in the
      bupropion and placebo arms, 37% versus 33%, respectively (p = .82). The validated
      quit rates for the bupropion and placebo groups were 27% versus 29%, respectively
      (p = 1.00). At 6 months, the self-reported quit rates were 29% in the bupropion
      group and 41% in the placebo group (p = .36). In a comparison of 6-month quit
      rates, validated either by salivary cotinine or by spousal proxy, we found
      nonsignificantly higher quit rates in the placebo group than in the bupropion
      group, 31% versus 15% (p = .12). DISCUSSION: The addition of sustained-release
      bupropion to counseling did not increase quit rates, but the study was
      underpowered. Because of the secular trend toward shorter hospital stays,
      recruitment was very difficult, raising questions regarding the feasibility of
      future hospital-based smoking cessation trials and interventions.

PMID- 19395689
TI  - Regulation of cell proliferation by the OGF-OGFr axis is dependent on nuclear
      localization signals.

PMID- 19395691
TI  - Optimal dosing and dynamic distribution of vaccines in an influenza pandemic.
AB  - Limited production capacity and delays inherent in vaccine development are major
      hurdles to the widespread use of vaccines to mitigate the effects of a new
      influenza pandemic. Antigen-sparing vaccines have the most potential to increase
      population coverage but may be less efficacious. The authors explored this trade
      off by applying simple models of influenza transmission and dose response to
      recent clinical trial data. In this paper, these data are used to illustrate an
      approach to comparing vaccines on the basis of antigen supply and inferred
      efficacy. The effects of delays in matched vaccine availability and
      seroconversion on epidemic size during pandemic phase 6 were also studied. The
      authors infer from trial data that population benefits stem from the use of low
      antigen vaccines. Delayed availability of a matched vaccine could be partially
      alleviated by using a 1-dose vaccination program with increased coverage and
      reduced time to full protection. Although less immunogenic, an overall attack
      rate of up to 6% lower than a 2-dose program could be achieved. However, if
      prevalence at vaccination is above 1%, effectiveness is much reduced, emphasizing
      the need for other control measures.

PMID- 19395692
TI  - Invited commentary: Lower urinary tract symptoms and inflammation--weighing the
      evidence.
AB  - Lower urinary tract symptoms (LUTS) are a common condition, particularly among
      older men. The etiology of these symptoms is often obscure and not always clearly
      related to prostatic enlargement or benign prostatic hyperplasia. St. Sauver et
      al. (Am J Epidemiol. 2009;169(11):1281-1290) hypothesized that systemic
      inflammation may be associated with LUTS and benign prostatic hyperplasia. Using
      a well-defined cohort, they found that, in general, inflammation was not related
      to LUTS or to benign prostatic hyperplasia progression. However, men with the
      highest amount of systemic inflammation, as measured by C-reactive protein
      levels, were at increased risk of a rapid change in irritative voiding symptoms
      and decreased urinary flow but not obstructive voiding symptoms or prostate size.
      To what degree systemic inflammation relates to inflammation within the urinary
      system and specifically the bladder and/or prostate is unclear. Furthermore, to
      what degree inflammation within the urinary system contributes to LUTS is
      unclear. Given that clinical trials of antiinflammatory drugs for LUTS have been
      largely unsuccessful, the role of inflammation as a contributor to LUTS remains
      an interesting hypothesis that requires further study.

PMID- 19395694
TI  - Re: "Advanced parental age and the risk of autism spectrum disorder".

PMID- 19395695
TI  - Association of early-life exposure to household gas appliances and indoor
      nitrogen dioxide with cognition and attention behavior in preschoolers.
AB  - The authors investigated the association of early-life exposure to indoor air
      pollution with neuropsychological development in preschoolers and assessed
      whether this association differs by glutathione-S-transferase gene (GSTP1)
      polymorphisms. A prospective, population-based birth cohort was set up in
      Menorca, Spain, in 1997-1999 (n = 482). Children were assessed for cognitive
      functioning (McCarthy Scales of Children's Abilities) and attention-hyperactivity
      behaviors (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) at
      age 4 years. During the first 3 months of life, information about gas appliances
      at home and indoor nitrogen dioxide concentration was collected at each
      participant's home (n = 398, 83%). Genotyping was conducted for the GSTP1 coding
      variant Ile105Val. Use of gas appliances was inversely associated with cognitive
      outcomes (beta coefficient for general cognition = -5.10, 95% confidence interval
      (CI): -9.92, -0.28; odds ratio for inattention symptoms = 3.59, 95% CI: 1.14,
      11.33), independent of social class and other confounders. Nitrogen dioxide
      concentrations were associated with cognitive function (a decrease of 0.27 point
      per 1 ppb, 95% CI: -0.48, -0.07) and inattention symptoms (odds ratio = 1.06, 95%
      CI: 1.01, 1.12). The deleterious effect of indoor pollution from gas appliances
      on neuropsychological outcomes was stronger in children with the GSTP1 Val-105
      allele. Early-life exposure to air pollution from indoor gas appliances may be
      negatively associated with neuropsychological development through the first 4
      years of life, particularly among genetically susceptible children.

PMID- 19395696
TI  - Obesity, lifestyle factors, and risk of myelodysplastic syndromes in a large US
      cohort.
AB  - The etiology of myelodysplastic syndromes (MDS) is not well understood. The
      authors examined the relations of obesity and lifestyle factors to MDS in a
      cohort of 471,799 persons aged 50-71 years who were recruited into the National
      Institutes of Health-AARP Diet and Health Study, a large US prospective study, in
      1995-1996. Incident MDS was diagnosed in 193 persons during 2001-2003. A
      significant positive association was observed between body mass index (BMI;
      weight (kg)/height (m)(2)) at baseline and MDS. Compared with persons with a BMI
      less than 25.0, the hazard ratios for persons with BMIs of 25.0-<30.0 and
      >or=30.0 were 1.15 (95% confidence interval (CI): 0.81, 1.64) and 2.18 (95% CI:
      1.51, 3.17; P for trend < 0.001), respectively. The association was not affected
      by physical activity, cigarette smoking, or alcohol intake. As reported in
      previous studies, the risk of MDS was elevated among former smokers (hazard ratio
      = 1.68, 95% CI: 1.17, 2.41) and current smokers (hazard ratio = 3.17, 95% CI:
      2.02, 4.98) as compared with never smokers. Physical activity, alcohol
      consumption, meat intake, and fruit and vegetable intake did not appear to
      significantly influence the risk of MDS in this analysis. This prospective
      investigation of MDS implicates both obesity and smoking as modifiable risk
      factors.

PMID- 19395699
TI  - Review: in vitro models for the study of early human embryo-endometrium
      interactions.
AB  - The molecular interactions at the embryo-endometrial interface during the period
      of blastocyst adhesion and subsequent invasion into the endometrial stroma are
      not fully understood. Current knowledge is primarily based on evidence from
      implantation studies in the mouse. The degree to which data derived from animal
      studies mirror human implantation is limited. The ethical and technical
      challenges studying implantation in the human can partly be overcome by designing
      in vitro models of embryo-endometrium interactions. In this review, the principal
      models in current use are described. Basic models using tissue explants and
      monolayers are distinguished from complex models using multilayer isolated cells,
      and embryo-endometrium coculture systems used therapeutically. Although there are
      limitations to current approaches, a number of research questions that could be
      addressed using these techniques are identified.

PMID- 19395697
TI  - Associations between C-reactive protein and benign prostatic hyperplasia/lower
      urinary tract symptom outcomes in a population-based cohort.
AB  - Inflammation may play a role in the development of benign prostatic hyperplasia
      and/or lower urinary tract symptoms (LUTS). Higher levels of C-reactive protein
      (CRP) may therefore be associated with the development of these outcomes. The
      authors examined the association of CRP levels measured in 1996 with rapid
      increases in prostate volume, prostate-specific antigen levels, and LUTS as well
      as rapid decreases in peak flow rates (through 2005) in a population-based cohort
      of men residing in Olmsted County, Minnesota. Men with CRP levels of > or =3.0
      mg/L were more likely to have rapid increases in irritative LUTS (odds ratio (OR)
      = 2.14, 95% confidence interval (CI): 1.18, 3.85) and rapid decreases in peak
      flow rates (OR = 2.54, 95% CI: 1.09, 5.92) compared with men with CRP levels of
      <3.0 mg/L. CRP levels were not significantly associated with rapid increases in
      prostate volume, obstructive LUTS, or prostate-specific antigen levels.
      Associations were attenuated after adjusting for age, body mass index,
      hypertension, and smoking history (irritative LUTS: OR = 2.00, 95% CI: 1.04,
      3.82; peak flow rate: OR = 2.45, 95% CI: 0.73, 8.25). These results suggest that
      rapid increases in irritative LUTS and rapid decreases in peak flow rates may be
      due to inflammatory processes.

PMID- 19395700
TI  - Multidisciplinary family meetings in the ICU facilitate end-of-life decision
      making.
AB  - OBJECTIVE: The aim of this study was to assess the feasibility of establishing a
      multi-disciplinary family meeting (MDFM) program and the impact of such a program
      on the end-of-life decision making in the setting of an ICU. METHODS: During the
      study period MDFMs were scheduled for patients requiring mechanical ventilation
      for 5 or more days. The meeting followed a structured format. The pertinent
      details of the meeting as well as the treatment goals were recorded. RESULTS:
      Twenty-nine patients were enrolled in this study. Thirty-five MDFM's were held on
      24 patients. A meeting could not be arranged for four patients. All meetings
      addressed patient's diagnosis, prognosis and goals of care. Fifteen (52%)
      patients (9 of whom had metastatic malignancy) had life support withdrawal and
      died a mean of 4.8 + 4.2 days after the first family meeting. In the remaining 9
      patients (3 with localized cancer and 6 with non-cancer diagnoses), the plan
      following the family meeting was to continue supportive care; all of these
      patients survived to hospital discharge. CONCLUSIONS: Proactive MDFM's improve
      communication and understanding between patients' family and the treating team
      and facilitates end-of-life decision making.

PMID- 19395702
TI  - Perinatal loss: impacting family grieving and nurse's self-fulfillment.

PMID- 19395701
TI  - Three lessons from a randomized trial of massage and meditation at end of life:
      patient benefit, outcome measure selection, and design of trials with terminally
      ill patients.
AB  - Improving end-of-life care is a priority in the United States, but assigning
      priorities for standard care services requires evaluations using appropriate
      study design and appropriate outcome indicators. A recent randomized controlled
      trial with terminally ill patients produced no evidence of benefit from massage
      or guided meditation, when evaluated with measures of global quality of life or
      pain distress over the course of patient participation. However, reanalysis using
      a more targeted outcome, surrogates' assessment of patients' benefit from the
      study intervention, suggested significant gains from massage-the treatment
      patients gave their highest preassignment preference ratings. The authors
      conclude that adding a menu of complementary therapies as part of standard end-of
      life care may yield significant benefit, that patient preference is an important
      predictor of outcome, and that modifications in trial design may be appropriate
      for end-of-life studies.

PMID- 19395703
TI  - Physician decision making: an observation.

PMID- 19395704
TI  - Formation of diapause cyst shell in brine shrimp, Artemia parthenogenetica, and
      its resistance role in environmental stresses.
AB  - Artemia has attracted much attention for its ability to produce encysted embryos
      wrapped in a protective shell when subject to extremely harsh environmental
      conditions. However, what the cyst shell is synthesized from and how the
      formative process is performed remains, as yet, largely unknown. Over 20
      oviparous specifically expressed genes were identified through screening the
      subtracted cDNA library enriched between oviparous and ovoviviparous Artemia
      ovisacs. Among them, a shell gland-specifically expressed gene (SGEG) has been
      found to be involved in the cyst shell formation. Lacking SGEG protein (by RNA
      interference) caused the cyst shell to become translucent and the chorion layer
      of the shell to become less compact and pultaceous and to show a marked decrease
      of iron composition within the shell. The RNA interference induced defective
      diapause cysts with a totally compromised resistibility to UV irradiation,
      extremely large temperature differences, osmotic pressure, dryness, and organic
      solvent stresses. In contrast, the natural cyst would provide adequate protection
      from all such factors. SGEG contains a 345-bp open reading frame, and its
      consequentially translated peptide consists of a 33-amino acid residue putative
      signal peptide and an 81-amino acid residue mature peptide. The results of
      Northern blotting and in situ hybridization indicate that the gene is
      specifically expressed in the cells of shell glands during the period of diapause
      cyst formation of oviparous Artemia. This investigation adds strong insight into
      the mechanism of cyst shell formation of Artemia and may be applicable to other
      areas of research in extremophile biology.

PMID- 19395705
TI  - Core3 O-glycan synthase suppresses tumor formation and metastasis of prostate
      carcinoma PC3 and LNCaP cells through down-regulation of alpha2beta1 integrin
      complex.
AB  - Although there are numerous reports of carbohydrates enriched in cancer cells,
      very few studies have addressed the functions of carbohydrates present in normal
      cells that decrease in cancer cells. It has been reported that core3 O-glycans
      are synthesized in normal gastrointestinal cells but are down-regulated in cancer
      cells. To determine the roles of core3 O-glycans, we transfected PC3 and LNCaP
      prostate cancer cells with beta3-N-acetylglucosaminyltransferase-6 (core3
      synthase) required to synthesize core3 O-glycans. Both engineered cell lines
      exhibited reduced migration and invasion through extracellular matrix components
      compared with mock-transfected cells. Moreover we found that alpha2beta1 integrin
      acquired core3 O-glycans in cells expressing core3 synthase with decreased
      maturation of beta1 integrin, leading to decreased levels of the alpha2beta1
      integrin complex, decreased activation of focal adhesion kinase, and reduced
      lamellipodia formation. Upon inoculation into the prostate of nude mice, PC3
      cells expressing core3 O-glycans produced much smaller tumors without metastasis
      to the surrounding lymph nodes in contrast to robust tumor formation and
      metastasis seen in mock-transfected PC3 cells. Similarly LNCaP cells expressing
      core3 O-glycans barely produced subcutaneous tumors in contrast to robust tumor
      formation by mock-transfected LNCaP cells. These findings indicate that addition
      of core3 O-glycans to beta1 and alpha2 integrin subunits in prostate cancer cells
      suppresses tumor formation and tumor metastasis.

PMID- 19395706
TI  - Proinsulin and the genetics of diabetes mellitus.
AB  - Insulin plays a central role in the regulation of vertebrate metabolism. The
      hormone, the post-translational product of a single-chain precursor, is a
      globular protein containing two chains, A (21 residues) and B (30 residues).
      Recent advances in human genetics have identified dominant mutations in the
      insulin gene causing permanent neonatal-onset DM(2) (1-4). The mutations are
      predicted to block folding of the precursor in the ER of pancreatic beta-cells.
      Although expression of the wild-type allele would in other circumstances be
      sufficient to maintain homeostasis, studies of a corresponding mouse model (5-7)
      suggest that the misfolded variant perturbs wild-type biosynthesis (8, 9).
      Impaired beta-cell secretion is associated with ER stress, distorted organelle
      architecture, and cell death (10). These findings have renewed interest in
      insulin biosynthesis (11-13) and the structural basis of disulfide pairing (14
      19). Protein evolution is constrained not only by structure and function but also
      by susceptibility to toxic misfolding.

PMID- 19395707
TI  - Identification of cellular proteome modifications in response to West Nile virus
      infection.
AB  - Flaviviruses are positive-stranded RNA viruses that are a public health problem
      because of their widespread distribution and their ability to cause a variety of
      diseases in humans. West Nile virus is a mosquito-borne member of this genus and
      is the etiologic agent of West Nile encephalitis. Clinical manifestations of West
      Nile virus infection are diverse, and their pathogenic mechanisms depend on
      complex virus-cell interactions. In the present work, we used proteomics
      technology to analyze early Vero cell response to West Nile infection. The
      differential proteomes were resolved 24 h postinfection using two-dimensional
      DIGE followed by mass spectrometry identification. Quantitative analysis (at
      least 2-fold quantitative alteration, p < 0.05) revealed 127 differentially
      expressed proteins with 68 up-regulated proteins and 59 down-regulated proteins
      of which 93 were successfully identified. The implication for mammalian cellular
      responses to this neurotropic flavivirus infection was analyzed and made possible
      more comprehensive characterization of the virus-host interactions involved in
      pathogenesis. The present study thus provides large scale protein-related
      information that should be useful for understanding how the host metabolism is
      modified by West Nile infection and for identifying new potential targets for
      antiviral therapy.

PMID- 19395708
TI  - Defective peroxisomal proliferators activated receptor gamma activity due to
      dominant-negative mutation synergizes with hypertension to accelerate cardiac
      fibrosis in mice.
AB  - AIMS: Humans with inactivating mutations in peroxisomal proliferators activated
      receptor gamma (PPARgamma) typically develop a complex metabolic syndrome
      characterized by insulin resistance, diabetes, lipodystrophy, hypertension, and
      dyslipidaemia which is likely to increase their cardiovascular risk. Despite
      evidence that the activation of PPARgamma may prevent cardiac fibrosis and
      hypertrophy, recent evidence has suggested that pharmacological activation of
      PPARgamma causes increased cardiovascular mortality. In this study, we
      investigated the effects of defective PPARgamma function on the development of
      cardiac fibrosis and hypertrophy in a murine model carrying a human dominant
      negative mutation in PPARgamma. METHODS AND RESULTS: Mice with a dominant
      negative point mutation in PPARgamma (P465L) and their wild-type (WT) littermates
      were treated with either subcutaneous angiotensin II (AngII) infusion or saline
      for 2 weeks. Heterozygous P465L and WT mice developed a similar increase in
      systolic blood pressure, but the mutant mice developed significantly more severe
      cardiac fibrosis to AngII that correlated with increased expression of
      profibrotic genes. Both groups similarly increased the heart weight to body
      weight ratio compared with saline-treated controls. There were no differences in
      fibrosis between saline-treated WT and P465L mice. CONCLUSION: These results show
      synergistic pathogenic effects between the presence of defective PPARgamma and
      AngII-induced hypertension and suggest that patients with PPARgamma mutation and
      hypertension may need more aggressive therapeutic measures to reduce the risk of
      accelerated cardiac fibrosis.

PMID- 19395709
TI  - Adherence to angiotensin-converting-enzyme inhibitors and illness beliefs in
      older heart failure patients.
AB  - AIMS: Patient beliefs about heart failure (HF) may be important determinants of
      adherence. This study assessed levels of adherence to angiotensin-converting
      enzyme inhibitors (ACEI) and examined whether beliefs about HF were associated
      with adherence to ACEI. METHODS AND RESULTS: Fifty-eight patients with chronic
      stable HF (mean age 80.2 years SD +/- 4.6, 43% female) were recruited from two
      outpatient clinics in Dundee, UK. The Illness Perception Questionnaire-Revised
      was used to assess beliefs about HF. Adherence to ACEI was assessed by measuring
      serum levels of angiotensin-converting enzyme (sACE). Adherence to ACEI (defined
      as sACE <5 U/L) was 72%. Beliefs about the time-line of HF and the consequences
      of HF accounted for 19% of the variability in adherence to ACEI in this sample.
      Heart failure patients who believed that their illness had a more chronic (longer
      term) time frame and had beliefs about the greater consequences of HF on their
      lives were less likely to adhere to ACEI. CONCLUSION: Adherence to ACEI is sub
      optimal. Beliefs about HF appear to be associated with objectively measured
      adherence to ACEI. Future studies should attempt to identify beliefs that
      consistently predict adherence and examine whether modifying these beliefs can
      increase adherence to HF medications.

PMID- 19395710
TI  - A hospital-randomized controlled trial of a formal quality improvement
      educational program in rural and small community Texas hospitals: one year
      results.
AB  - OBJECTIVE: To investigate the effectiveness of a quality improvement educational
      program in rural hospitals. DESIGN: Hospital-randomized controlled trial.
      SETTING:  PARTICIPANTS: A total of 47 rural and small community hospitals in
      Texas that had previously received a web-based benchmarking and case-review tool.
      INTERVENTION: The 47 hospitals were randomized either to receive formal quality
      improvement educational program or to a control group. The educational program
      consisted of two 2-day didactic sessions on continuous quality improvement
      techniques, followed by the design, implementation and reporting of a local
      quality improvement project, with monthly coaching conference calls and annual
      follow-up conclaves. MAIN OUTCOME MEASURES: Performance on core measures for
      community-acquired pneumonia and congestive heart failure were compared between
      study groups to evaluate the impact of the educational program. RESULTS: No
      significant differences were observed between the study groups on any measures.
      Of the 23 hospitals in the intervention group, only 16 completed the didactic
      program and 6 the full training program. Similar results were obtained when these
      groups were compared with the control group. CONCLUSIONS: While the observed
      results suggest no incremental benefit of the quality improvement educational
      program following implementation of a web-based benchmarking and case-review tool
      in rural hospitals, given the small number of hospitals that completed the
      program, it is not conclusive that such programs are ineffective. Further
      research incorporating supporting infrastructure, such as physician champions,
      financial incentives and greater involvement of senior leadership, is needed to
      assess the value of quality improvement educational programs in rural hospitals.

PMID- 19395711
TI  - Radiation protection in inhomogeneous beta-gamma fields and modelling of hand
      phantoms with MCNPX.
AB  - The usage of beta-radiation sources in various nuclear medicine therapies is
      increasing. Consequently, enhanced radiation protection measures are required, as
      medical staff more frequently handle high-activity sources required for therapy.
      Inhomogeneous radiation fields make it difficult to determine absorbed dose
      reliably. Routine monitoring with dosimeters does not guarantee any accurate
      determination of the local skin dose (LSD). In general, correction factors are
      used to correct for the measured dose and the maximum absorbed dose received.
      However, strong underestimations of the maximum exposure are possible depending
      on the individual handling the process and the reliability of dose measurements.
      Simulations can be used as a tool for a better understanding of the maximum
      possible exposure depending on the individual-related handling. While
      measurements reveal the overall dose during the entire irradiation time of the
      dosimeter, simulations help to analyse sequences of action. Hence, simulations
      allow for tracking the points of highest absorbed dose received during the
      handling process. In this respect, simulations were performed using the MCNPX
      software. In order to investigate the LSD, two hand phantoms were used, a model
      based on geometrical elements and a voxel hand. A typical situation of
      radiosynoviorthesis, i.e. handling a syringe filled with (90)Y, was simulated.
      The results of the simulations show that the annual dose limit may be exceeded
      within minutes at the position of maximum absorbed dose received and that finger
      ring dosimeters measure significantly different doses depending on their wearing
      position. It is of essential importance to wear the dosimeter properly and to use
      suitable correction factors with respect to the individual. Simulations are a
      suitable tool for ensuring reliable dose determination and may help to derive
      recommendations regarding radiation protection measures.

PMID- 19395715
TI  - Border disease virus isolated from a bovine fetus.

PMID- 19395716
TI  - Application of a protocol for the diagnosis of postweaning multisystemic wasting
      syndrome in Italy.
AB  - Samples of superficial inguinal and bronchial lymph nodes, ileum, tonsil and lung
      were taken from three to five pigs on each of 61 farms with a clinical history of
      postweaning multisystemic wasting syndrome (PMWS). The samples were examined
      histologically and by immunohistochemistry for porcine circovirus type 2 (PCV-2).
      PMWS was diagnosed in two stages: first, an evaluation of the haematoxylin and
      eosin-stained sections that identified the cases in which the characteristic PCV
      2 cytoplasmic inclusion bodies were apparent, and secondly, a conclusive step in
      which immunohistochemistry was applied to confirm PMWS in the cases in which
      there were positive immunohistochemical results that coincided with lesions
      indicative of PMWS in at least one of the lymphoid and/or lung tissues. The
      location of PCV-2 in specific lesions (cell depletion in lymphoid organs and
      interstitial pneumonia) confirmed PMWS in 45 of the 61 farms, 31 of which were
      also infected with porcine reproductive and respiratory syndrome virus. The
      lymphoid tissues were more reliable than the lungs for the diagnosis of PMWS,
      both in individual pigs and in groups of pigs, and farm diagnoses based on a
      group of pigs were more reliable than diagnoses based on single pigs.

PMID- 19395717
TI  - Histological assessment of testicular residues in lambs and calves after Burdizzo
      castration.
AB  - To assess the reliability of the Burdizzo procedure for castrating calves and
      lambs, testicular tissue from 63 bull calves (15 intact and 48 castrated) and 69
      male lambs (35 intact and 34 castrated) was collected at slaughter and assessed
      histologically. The bull calves were castrated at either one, four to five or 12
      to 16 weeks of age and the lambs at either one or 10 weeks. There was clear
      evidence of spermatogenesis in testicular tissue from all the intact animals. In
      the samples from the calves that had been castrated at 12 to 16 weeks functional
      testicular tissue was completely lacking. However, there was evidence of
      spermatogenesis and steroidogenesis in the calves that had been castrated at one
      week or four to five weeks, respectively. Failure to achieve complete involution
      of the testicular parenchyma was observed in the majority of lambs, irrespective
      of the age at which they had been castrated.

PMID- 19395718
TI  - First cases of squirrelpox in red squirrels (Sciurus vulgaris) in Scotland.
AB  - Squirrelpox, caused by a poxvirus, is a major threat to the remaining UK red
      squirrel population. The spread of antibody-positive grey squirrels has been
      monitored in the UK for the past decade. In 2005 grey squirrels that had been
      exposed to the virus appeared in the south of Scotland for the first time,
      followed approximately two years later by the appearance of squirrelpox disease
      in the local red squirrels. Four squirrels were examined. They all had gross
      external lesions and histological lesions typical of squirrelpox disease, but no
      significant internal lesions. The diagnosis was confirmed by PCR, electron
      microscopy and serology.

PMID- 19395719
TI  - Inactivation of avian influenza virus H5N2 in acidified chicken pulp.

PMID- 19395720
TI  - Neonatal blood lactate concentration and calf morbidity.

PMID- 19395721
TI  - Nasal bone osteochondroma in a horse.

PMID- 19395722
TI  - Signing and stamping of official veterinary certification.

PMID- 19395723
TI  - Register of interested parties to provide service in times of emergency.

PMID- 19395724
TI  - Proposed veterinary union.

PMID- 19395725
TI  - Canine angiostrongylosis in northern England.

PMID- 19395726
TI  - Moderate-to-severe early-onset hyperuricaemia: a prognostic marker of long-term
      kidney transplant outcome.
AB  - BACKGROUND: Hyperuricaemia commonly occurs in renal transplant recipients (RTRs),
      but the effects of post-transplant hyperuricaemia on kidney transplant outcome
      have not been clearly established. This work was designed to explore the impact
      of hyperuricaemia on renal transplant outcome. METHODS: The authors examined this
      issue by analysing the clinical outcome of 281 RTRs. Hyperuricaemia (defined as
      UA > 7.0 mg/dl in men and >6.0 mg/dl in women for at least two consecutive tests,
      n = 121) was classified as early onset (within 1 year of transplant, n = 90) or
      late onset (n = 31). Graft function was estimated using the MDRD Study Equation 7
      (eGFR(MDRD)). RESULTS: As late-onset hyperuricaemia was found to be induced by a
      progressive decline in the graft function (P < 0.01), data from early-onset
      hyperuricaemic recipients were used. Early-onset moderate-to-severe
      hyperuricaemia (defined as UA >or= 8.0 mg/dl) was found to be a significant risk
      factor for chronic allograft nephropathy (P = 0.035) and a poorer graft survival
      (P = 0.026) by multivariate analysis, whereas mild hyperuricaemia was not. The
      impact of moderate-to-severe hyperuricaemia on renal transplant survival was
      dependent on the duration of exposure. Likewise, the detrimental effect of early
      onset hyperuricaemia on the graft function was dependent on UA levels and
      exposure time. After control of the baseline graft function by analysis of only
      recipients with a good graft function at 1 year post-transplantation (eGFR(MDRD)
      > 60 ml/min), moderate-to-severe early-onset hyperuricaemia was also found to be
      a marker of long-term graft dysfunction and failure. CONCLUSION: Moderate-to
      severe early-onset hyperuri- caemia may be a prognostic marker of the long-term
      graft outcome in RTRs, which needs further investigation.

PMID- 19395727
TI  - Cystatin C is correlated with mortality in patients with and without acute kidney
      injury.
AB  - BACKGROUND: Recent research has shown cystatin C to predict mortality and
      cardiovascular morbidity independent of renal function. The aim of this study was
      to evaluate the prognostic value of cystatin C on mortality in adult general ICU
      patients with acute kidney injury (AKI). We later expanded the study and included
      patients without signs of AKI. METHODS: A total of 845 ICU patients were analysed
      for cystatin C and classified according to the RIFLE criteria. Of these, 271
      patients with either creatinine >150 micromol/l, urea >25 or anuria/oliguria
      entered the AKI cohort. The remaining 562 patients entered the non-AKI cohort.
      Both cohorts were divided into quartiles according to cystatin C at entry. In the
      non-AKI cohort, we split the highest cystatin C quartile into two. The
      relationship between the different cystatin C quartiles and mortality in patients
      with and without AKI was estimated by hazard ratios (HR) derived from the Cox
      proportional hazards regression model. RESULTS: A relationship between cystatin C
      and mortality was found in patients with and without AKI, being stronger in
      patients without AKI. In AKI patients, the HR comparing cystatin C above and
      below the median more than doubled from the second year on compared to the first
      year follow-up. After exclusion of patients in the non-AKI cohort with 'potential
      AKI' (creatinine >100 micromol/l or urea > 20 mmol/l), the correlation between
      cystatin C levels and risk of death was strengthened. CONCLUSIONS: Cystatin C is
      correlated with mortality independently of renal function measured by creatinine
      in patients entering the general ICU.

PMID- 19395728
TI  - An easy to calculate equation to estimate GFR based on inulin clearance.
AB  - BACKGROUND: For the estimation of renal function on the basis of serum
      creatinine, either the Cockcroft-Gault (CG) equation or the MDRD formula is
      commonly used. Compared to MDRD (using power functions), CG has the advantage of
      easy calculability at the bedside. MDRD, however, approaches glomerular
      filtration rate (GFR) more precisely than CG and gives values corrected for a
      body surface area (BSA) of 1.73 m(2). We wondered whether CG could be adapted to
      estimate GFR rather than creatinine clearance without losing the advantage of
      easy calculability. In this prospective study, inulin clearance under well
      defined conditions was taken as the gold standard for GFR. METHODS: In 182 living
      kidney donors, inulin clearance was measured under standardized conditions
      (protein, salt and water intake, overnight stay) before and after nephrectomy.
      Together with the serum creatinine level, and demographic and clinical data, 281
      measurements of inulin clearance were used to compare the accuracy of different
      estimation equations. Using stepwise multiple regression, a new set of constants
      was defined for a CG-like equation in order to estimate GFR. RESULTS: The MDRD
      equation underestimated GFR by 9%, and the quadratic equation suggested by Rule
      overestimated GFR by 12.4%. The new CG-like equation, even when calculated with
      'mental arithmetic-friendly' rounded parameters, showed significantly less bias
      (1.2%). The adapted equation is GFR[mL/min] = ((155 - Age[years]) x weight
      [kg]/serum creatinine [micromol/L]) x 0.85 if female. CONCLUSIONS: We propose the
      CG-like equation called IB-eGFR (Inulinclearance Based eGFR) to estimate GFR more
      reliably than MDRD, Rule's equation or the original Cockcroft-Gault equation. As
      our data represent a Caucasian population, the adapted equation is still to be
      validated for patients of other ethnicity.

PMID- 19395729
TI  - Cell division and phenotypic regression of proximal tubular cells in response to
      uranyl acetate insult in rats.
AB  - BACKGROUND: We examined whether dedifferentiation is necessary for cell division
      of proximal tubule (PT) cells after acute PT injury. METHODS: Rats were injected
      with a low (0.2 mg/kg) or high (4 mg/kg) dose of uranyl acetate (UA) to induce
      acute PT injury. Proliferating PT cells were labelled with bromodeoxyuridine
      (BrdU) before sacrifice. Renal tissues were examined by double labelling of BrdU
      and megalin, aquaporin 1 (AQP1), Na(+)-K(+)ATPase or vimentin, and by
      immunoelectron microscopy for BrdU+ cells. RESULTS: Under normal conditions,
      BrdU+ PT cells were positive for the PT phenotype (megalin-, AQP1- and Na(+)
      K(+)ATPase positive and vimentine negative, a mesenchymal marker). Low-dose UA
      induced focal PT injury, and BrdU+ initially proliferating PT cells were found in
      the proximal three quarters of the S3 segment of nephron as early as 12 h, which
      maintained the PT phenotype and were vimentin negative. Proliferating PT cells
      showed low expression of the PT cell protein phenotype from Day 2 to Day 5 with
      vimentin expression from Day 2. High-dose UA induced severe PT injury in the
      proximal three quarters of the S3 segment by Day 5. BrdU+ initially proliferating
      PT cells, which were found in distal areas of the S3 segment as early as Day 2,
      showed low expression of the PT protein phenotype but were vimentin positive.
      Immunoelectron microscopy showed mature PT morphology for BrdU+ PT cells in
      control rats. BrdU+ initially proliferating PT cells showed a relatively mature
      phenotype after low-dose UA in- sult but an immature phenotype after high-dose UA
      insult. CONCLUSIONS: PT cells can initiate cell division without de-
      differentiation after mild PT injury by low-dose UA insult.

PMID- 19395730
TI  - High levels of serum fibroblast growth factor (FGF)-23 are associated with
      increased mortality in long haemodialysis patients.
AB  - BACKGROUND: Fibroblast growth factor (FGF)-23, a novel bone-derived phosphaturic
      factor involved in mineral metabolism, is increased in chronic kidney disease
      (CKD); in dialysis patients, it has been linked to increased mortality rates and
      vascular calcification (VC). The present investigation aimed to study the factors
      associated with elevated serum FGF-23 levels in patients treated with long
      haemodialysis (LHD) sessions and to determine whether a relationship exists
      between serum FGF-23 levels and patient survival. METHODS: All patients treated
      in one haemodialysis centre from September 2006 were included in the study.
      Standard laboratory values, medical history, cardiovascular events and risk
      factors, medication and FGF-23 levels [ELISA (C-Term) Immutopics] were recorded.
      Patients received haemodialysis three times a week, on a 5- to 8-h schedule.
      Patient data were analysed according to FGF-23 quartiles. The effect of FGF-23 on
      the 2-year survival rate was assessed using the Cox proportional hazard model,
      adjusted for confounding variables and according to the serum phosphate tertiles.
      RESULTS: The study included 219 patients. Serum FGF-23 levels were high: 7060 +/-
      13 500 RU/mL (median, 2740 RU/mL). In logistical regressions, only calcaemia (P =
      0.002), phosphataemia (P = 0.008) and warfarin use (P = 0.04) were associated
      with the highest FGF-23 quartile. In the subgroup of patients with an estimated
      VC score, the third and fourth quartiles of the FGF-23 levels were associated
      with more severe VC. In multivariate linear regressions, only phosphataemia
      remained significantly correlated with FGF-23 (P = 0.04). The 2-year mortality
      rate was significantly higher for haemodialysis patients with serum FGF-23 levels
      in the higher quartile [P = 0.007; hazard ratio, 2.5 (1.3-5)] than in the first
      quartile, whereas within the phosphataemia tertiles, the lowest serum FGF-23
      quartile was associated with lowered mortality. CONCLUSION: This study
      demonstrated a high level of circulating FGF-23 in LHD patients, despite
      infrequent hyperphosphataemia. However, phosphataemia is still the main factor
      correlating with serum FGF-23. The association of higher serum FGF-23 levels with
      mortality and VC, regardless of the serum phosphate levels, has thus been
      confirmed.

PMID- 19395731
TI  - Diffuse proliferative glomerulonephritis does not determine the worst outcome in
      childhood-onset lupus nephritis: a 23-year experience in a single centre.
AB  - INTRODUCTION: Lupus nephritis (LN) is the major indicator of morbidity and
      mortality in systemic lupus erythematosus (SLE). Many studies have found a
      significantly worse patient survival rate in patients with LN class IV than
      patients with other LN classes. OBJECTIVE: The aim was to describe the severity
      and outcomes of LN in a group of Thai children. METHODS: We retrospectively
      reviewed the patient files of children diagnosed with SLE aged < or =18 years in
      Songklanagarind Hospital, Southern Thailand, from 1985 to 2007. RESULTS: Of 216
      SLE patients, 180 had renal biopsy results, and the others were excluded from
      analysis. There were 33 males and 147 females, average age 11.8 +/- 2.6 years
      (range 3.6-18.0), with a median follow-up period of 3.9 years (range 9 days to
      19.4 years). Using the WHO LN classification, there were 9, 55, 5, 94 and 14
      patients of classes I-V, respectively, as well as 2 with end-stage renal disease
      and 1 with IgM nephropathy. The mortality rate was 23% (42/180). Patients with LN
      class II had a similar renal and patient survival compared to patients with LN
      class IV (P = 0.3 and 0.2, respectively). Cox proportional hazard regression
      analysis in 177 patients (3 patients who had a renal biopsy result outside the
      WHO classification were omitted) showed that gender was an independent risk
      factor for survival. Males had 2.6 times the hazard rate compared to females (95%
      CI 1.2-5.7, P = 0.03), but LN classification, age and timing of the renal biopsy
      were not significant. CONCLUSION: Renal and patient survival in LN classes II and
      IV were similar. Gender was the only independent risk factor of mortality, with
      males at greater risk than females.

PMID- 19395732
TI  - Short-term outcomes of borderline stenoses in vascular accesses with PTFE grafts.
AB  - BACKGROUND: There are controversial data about vascular access stenosis
      surveillance by ultrasonography. The definition of stenosis significance varies
      among centres. We performed a retrospective study to describe short-term outcomes
      of borderline asymptomatic stenoses defined by precise criteria and to determine
      possible risk factors of stenosis progression. METHODS: We studied the outcome of
      borderline stenoses in accesses with PTFE grafts. Stenosis was considered
      significant if there was a combination of >50% lumen reduction and peak systolic
      ratio >2, together with at least one of the following additional criteria: (1)
      residual diameter <2.0 mm and (2) flow reduction of >25% or actual flow volume
      <600 ml/min. Stenosis was considered borderline in the absence of the additional
      criteria. RESULTS: Of the 102 borderline stenoses, after 11 +/- 6 weeks, 55
      remained non-progressive, in 38 the degree of the stenosis progressed, in 8 a
      percutaneous transluminal angioplasty (PTA) was performed due to clinical
      indication and only 1 thrombosed. A significant relative risk of developing
      significant stenosis was found in grafts with prior PTA [RR = 1.91 (95% CI: 1.27,
      2.88), P = 0.002] and in female gender [RR = 2.29, (95% CI: 1.29, 4.06), P =
      0.025]. CONCLUSIONS: Delaying PTA of borderline stenoses is safe using this watch
      and-wait strategy and stenoses remain stable over at least short time, but with
      higher risk of progression especially after prior PTA. We believe that the
      definition of precise criteria of stenosis significance is necessary for the
      benefit of ultrasound surveillance.

PMID- 19395733
TI  - Letter to the editor regarding 'Acute phase reaction to gadolinium-DTPA in
      dialysis patients'.

PMID- 19395734
TI  - LXR and ABCA1 control cholesterol homeostasis in the proximal mouse epididymis in
      a cell-specific manner.
AB  - Mammalian spermatozoa undergo important plasma membrane maturation steps during
      epididymal transit. Among these, changes in lipids and cholesterol are of
      particular interest as they are necessary for fertilization. However, molecular
      mechanisms regulating these transformations inside the epididymis are still
      poorly understood. Liver X receptors (LXRs), the nuclear receptors for
      oxysterols, are of major importance in intracellular cholesterol homeostasis, and
      LXR(-/-)-deficient male mice have already been shown to have reduced fertility at
      an age of 5 months and complete sterility for 9-month-old animals. This sterility
      phenotype is associated with testes and caput epididymides epithelial defects.
      The research presented here was aimed at investigating how LXRs act in the male
      caput epididymidis by analyzing key actors in cholesterol homeostasis. We show
      that accumulation of cholesteryl esters in LXR(-/-) male mice is associated with
      a specific loss of ABCA1 and an increase in apoptosis of apical cells of the
      proximal caput epididymidis. ATP-binding cassette G1 (ABCG1) and scavenger
      receptor B1 (SR-B1), two other cholesterol transporters, show little if any
      modifications. Our study also revealed that SR-B1 appears to have a peculiar
      expression pattern along the epididymal duct. These results should help in
      understanding the functional roles of LXR in cholesterol trafficking processes in
      caput epididymidis.

PMID- 19395735
TI  - Experimental infection of Hawai'i 'Amakihi (hemignathus virens) with West Nile
      virus and competence of a co-occurring vector, culex quinquefasciatus: potential
      impacts on endemic Hawaiian avifauna.
AB  - Introduced mosquito-borne avian disease is a major limiting factor in the
      recovery and restoration of native Hawaiian forest birds. Annual epizootics of
      avian pox (Avipoxvirus) and avian malaria (Plasmodium relictum) likely led to the
      extinction of some species and continue to impact populations of susceptible
      Hawaiian honeycreepers (Drepanidinae). The introduction of a novel pathogen, such
      as West Nile virus (WNV), could result in further population declines and
      extinctions. During September and October 2004, we infected Hawai'i' Amakihi
      (Hemignathus virens) with a North American isolate of WNV by needle inoculation
      and mosquito bite to observe susceptibility, mortality, and illness in this
      endemic passerine, and to determine the vector competence of the co-occurring,
      introduced mosquito Culex quinquefasciatus. All experimentally infected Hawai'i
      ;Amakihi became viremic, with a mean titer >10(5) plaque-forming units (PFU)/ml,
      and they experienced clinical signs ranging from anorexia and lethargy to ataxia.
      The fatality rate among needle-inoculated Hawai'i' Amakihi (n=16) was 31.3%, but
      mortality in free-ranging birds is likely to increase due to predation,
      starvation, thermal stress, and concomitant infections of avian malaria and pox.
      Surviving Hawai'i' Amakihi seem to clear WNV from the peripheral blood by 7-10
      days postinfection (DPI), and neutralizing antibodies were detected from 9 to 46
      DPI. In transmission trials, Hawaiian Cx. quinquefasciatus proved to be a
      competent vector and Hawai'i Amakihi an adequate amplification host of WNV,
      suggesting that epizootic WNV could readily become an additional limiting factor
      of some native Hawaiian bird populations.

PMID- 19395736
TI  - Transmission of lungworms (Muellerius capillaris) from domestic goats to bighorn
      sheep on common pasture.
AB  - Four domestic goats (Capra hircus) that were passing first-stage dorsal-spined
      larvae of Muellerius capillaris were copastured on a 0.82-ha pasture for 11 mo
      from May 2003 to April 2004 with seven Rocky Mountain bighorn sheep (Ovis
      canadensis) that were not passing dorsal-spined larvae. During the 11-mo
      experiment, two bighorn sheep died from pneumonia caused by Mannheimia
      (Pasteurella) haemolytica biotype A, serotype 2. The remaining five bighorn sheep
      and the four domestic goats remained healthy throughout the experiment.
      Muellerius larvae were detected from all domestic goats on a monthly basis
      throughout the experiment and were first detected from all five surviving bighorn
      sheep approximately 5 mo after the copasturing began. Once the bighorn sheep
      began passing Muellerius larvae, larvae were detected in low numbers from all
      bighorn sheep every month thereafter for the 6 mo the goats were still in the
      enclosure and continued to pass larvae for more than 3 yr after the goats were
      removed from the experiment. Six bighorn sheep in two similar enclosures that did
      not contain goats did not pass Muellerius larvae before, during, or after the
      experimental period. Results of this experiment indicate that M. capillaris from
      domestic goats is capable of infecting bighorn sheep when animals are copastured
      together on a common range.

PMID- 19395737
TI  - The carriage of larval echinococcus multilocularis and other cestodes by the musk
      rat (Ondatra zibethicus) along the Ourthe River and its tributaries (Belgium).
AB  - In Belgium, the carriage of Echinococcus multilocularis by the red fox (Vulpes
      vulpes) can be very high in some areas. This study was designed to evaluate the
      carriage of the larval form of E. multilocularis and other cestodes in a musk rat
      (Ondatra zibethicus) population trapped along the Ourthe River (southeastern
      Belgium). Six hundred fifty-seven musk rats were necropsied, and the larval
      cestodes of the abdominal and pleural cavities were identified. For E.
      multilocularis, the fertility of the cysts was verified in 58 liver samples. The
      following species were found: Taenia taeniaeformis (65.8%), Taenia martis
      (22.2%), E. multilocularis (22.1%), Taenia polyacantha (2.6%), and Taenia
      crassiceps (0.9%). Results were analyzed according to the site of capture (upper,
      middle, and lower Ourthe). There was a highly significant relationship between
      the carriage of E. multilocularis and the site of capture (the prevalence being
      higher in the upper part of the river). This difference could be due to different
      geoclimatic conditions. All but one hepatic lesion were found to contain
      protoscoleces of E. multilocularis (98.8%). The musk rat is probably infected
      through the consumption of plant material contaminated by the fox's feces. The
      red fox can occasionally prey on musk rats, but the musk rat cadavers that are
      left on the river banks by the trappers are probably also consumed. This could
      favor the maintenance of E. multilocularis life cycle. In conclusion, the musk
      rat seems to be highly susceptible to E. multilocularis and in Belgium could play
      the role of reservoir; when present this species could represent an inexpensive
      and sensitive bioindicator for the study and monitoring of the zoonosis.

PMID- 19395738
TI  - Parasite species associated with wild plateau pika (Ochotona curzoniae) in
      southeastern Qinghai Province, China.
AB  - A survey was conducted to determine the prevalence and seasonal abundance of egg,
      larval, and adult stages of helminths; oocyts of protozoans; and ectoparasites of
      plateau pikas (Ochotona curzoniae) in seven areas of southeastern Qinghai
      Province, China, during August 2006 and May 2007. Fecal samples collected from
      430 plateau pikas were examined by the modified McMaster technique, which
      revealed that 83% of the samples contained eggs from two or more helminth
      species. Mean fecal egg counts were generally moderate and showed the same trend
      irrespective of the age or sex of the pikas. The prevalence and counts of cestode
      eggs showed strong seasonal relationships that corresponded with the rainfall
      pattern in the study area during the study period. Of the 430 plateau pika
      examined at necropsy, 89% contained adult nematode or cestode species, but none
      of these contained adult trematode species or protozoans. Overall, six genera of
      adult nematodes including Oesophagostomum sp., Cephaluris coloradensis, Eugenuris
      schumakowiescsi, Haemonchus sp., Trichuris sp., and Chbertiinae sp.; three genera
      of adult cestodes including Schizorchis sp., Ochotonae sp., and Hymenolepis nana;
      three ectoparasite species including Hypoderma curzonial, Pulex sp., and Ixodes
      ovatus; and one proscolex stage of a cestode, Echinococcus multilocularis or
      Echinococcus shiquicus, were encountered during the study. Other genera examined
      occurred in low numbers, which did not allow any meaningful comparisons. Overall,
      results suggest that four parasite species, Hypoderma curzonial, Pulex sp.,
      Ixodes ovatus Neumann, and Cephaluris coloradensis, may be regulating factors in
      controlling future numbers of plateau pika in this study area. These data provide
      evidence of a natural biologic control mechanism of plateau pika on grassland
      habitats, and may be of use for identifying the mechanism of transmission of
      parasites between plateau pika, livestock, and humans.

PMID- 19395739
TI  - First isolation of mycobacterium avium subsp. Paratuberculosis from wild guanacos
      (Lama guanicoe) on Tierra del Fuego Island.
AB  - The aim of this study was to search for Mycobacterium avium subsp.
      paratuberculosis (Map) infection in a free-ranging wild animal species in a
      region where Johnes's disease has yet to be reported and to classify Map isolates
      using a genomic typing method. Fecal samples were obtained from 501 wild guanacos
      (Lama guanicoe) from Tierra del Fuego Island, Chile, in August 2006. Samples were
      cultured using Herrold's egg yolk medium with and without mycobactin J. After 9
      mo of incubation, suspected Map colonies showing mycobactin dependence were
      confirmed by real-time polymerase chain reaction (PCR) based on IS900 and F57.
      Isolates were further tested using IS1311 PCR with restriction endonuclease
      analysis in order to type the guanaco Map strains. Twenty-one of 501 (4.2%)
      animals were fecal culture-positive for Map; identity was confirmed by real-time
      PCR and isolates were classified as cattle-type. Most culture-positive animals
      were located in four contiguous geographic areas, and the infection was most
      commonly found among adult animals. Prevalence was higher in females (5.9%) than
      males (3.1%) but the difference was not statistically significant. This
      represents the first isolation of Map from a free-ranging wildlife species in
      Chile. It expands the geographic range of paratuberculosis and the diversity of
      wildlife species that can become infected with Map.

PMID- 19395740
TI  - Prevalence and antibiotic-resistance characteristics of Enterococcus spp.
      Isolated from free-living and captive raptors in Central Illinois.
AB  - Due to their predatory nature, raptor species may serve as important indicators
      of environmental contamination with antimicrobial-resistant bacteria. Raptors
      prey on small rodents and birds that have diverse habitat ranges, including urban
      and rural environments, and their intestinal microflora can reflect that of the
      animals on which they feed. Enterococcus spp. were selected as target organisms
      because they have been isolated from the avian gastrointestinal tract, can be
      conferred by prey items, and because they are capable of multiple resistance
      patterns. They are also a concerning source of human antimicrobial resistance. In
      this study fecal cultures were obtained from 15 May 2004 to 31 August 2004, from
      21 free-living raptors and four captive raptors. Enterococcus was isolated from
      21 (84%) of the 25 birds, and 54 isolates were chosen for further study based
      upon unique colony morphology. The most common isolate recovered was Enterococcus
      faecalis (95%, 95% confidence interval [CI]: 89-100). One bird in the study was
      determined to have Enterococcus gallinarum. Two distinct ribotypes of E. faecalis
      were identified, one with unique bands at 11 and 13 kb and the other with unique
      bands at 14 and 20 kb. Both ribotypes were found in free-living and captive
      birds. The Enterococcus isolates in this study demonstrated a variety of
      antimicrobial-resistance characteristics, including almost complete resistance to
      amikacin, first-generation cephalosporins, spectinomycin, and sulphadimethoxime.
      Isolates demonstrated variable resistance to chloramphenicol, gentamicin,
      enrofloxacin, erythromycin, and ticarcillin. No phenotypically vancomycin
      resistant E. faecalis isolates were recovered from any of the raptors; three
      isolates had intermediate level susceptibility. A significantly higher number of
      isolates collected from captive birds demonstrated resistance to chloramphenicol
      than those obtained from free-living birds. This trend was not duplicated with
      any of the remaining 18 antimicrobial drugs tested. The results of this study
      suggest that raptors in central Illinois are coming into contact with
      antimicrobials, prey exposed to antimicrobials, or bacteria that are capable of
      transferring resistance genes. Further study is needed to determine the source of
      antimicrobial-resistant Enterococcus in free-living raptors but the limited data
      reflecting few differences between birds with and without antimicrobial exposure
      suggests that treatment and release of treated wild raptors is not contributing
      significantly to antimicrobial resistance in the environment.

PMID- 19395741
TI  - Pathologic findings in larval and juvenile anurans inhabiting farm ponds in
      Tennessee, USA.
AB  - Amphibian populations are declining globally, yet general pathologic surveys for
      free-ranging amphibians are uncommon. Pathologic surveys are necessary to provide
      insight into the impacts of humans on emergence of pathogens in amphibian
      populations. During 2005, 104 American bullfrog (Rana catesbeiana) and 80 green
      frog (Rana clamitans) larvae and 40 green frog juveniles were collected from farm
      ponds in Tennessee, and complete necropsies were performed. Diagnostic testing
      included bacterial culture, virus testing, fecal parasite analysis, and
      histologic examination. Gross and histologic examination revealed that all
      individuals, except one bullfrog tadpole, could be classified as clinically
      normal. The clinically abnormal tadpole had swollen erythemic legs, and was
      positive for Aeromonas hydrophila but negative for Ranavirus. Parasites were
      common (43%) among specimens, with myxosporidium and trematodes most often noted.
      Commensal and opportunistic microorganisms were cultured from the tissues.
      Ranavirus was detected in 29% of individuals but generally not associated with
      significant histopathologic changes. Myxosporidia and Ranavirus coinfections
      occurred in 7 and 26% of green and bullfrog tadpoles, respectively, with the
      highest coinfection rate (83%) in bullfrog tadpoles during winter. Protozoans
      were most common in fecal examination. These data can serve as a baseline to
      evaluate the presence of clinical disease in larval and juvenile amphibians.

PMID- 19395742
TI  - Skeletal lesions in a population of Virginia opossums (Didelphis virginiana) from
      Baldwin County, Georgia.
AB  - Antemortem skeletal lesions were analyzed in 61 Virginia opossums (Didelphis
      virginiana) collected as roadkill from Baldwin County, Georgia, USA. As evidenced
      by bridging fracture calluses, misalignments, bone-surface depressions,
      perforations, localized superficial calluses, periosteal proliferations, and bony
      bridges across intervertebral disk spaces, 64% of the individuals had signs of
      one or more healed injuries. Within the subset of skeletons with bone lesions,
      54% had healed rib fractures and 23% had scapular, 21% pelvic, 18% fibular, 18%
      vertebral, 13% dentary, 10% tibial, and 10% podial lesions. Bone lesions occurred
      most frequently in the cranial portion of the skeletons and averaged
      approximately four per individual. The majority of the skeletal injuries appeared
      to be inconsistent with those caused by falls or automobile collisions. The
      nature and position of the bone lesions suggested that nonfatal predator attacks,
      possibly from domestic dogs, may be a significant contributor to bodily injury in
      this species.

PMID- 19395743
TI  - A suspected canine distemper epidemic as the cause of a catastrophic decline in
      Santa Catalina Island foxes (Urocyon littoralis catalinae).
AB  - The island fox (Urocyon littoralis catalinae) population on Santa Catalina
      Island, California, USA declined precipitously in 1999 with an approximate 95%
      reduction on their eastern range, an area representing 87% of the island. During
      this investigation, between October 1999 and April 2000, evidence of live foxes
      dramatically decreased. The only carcass recovered during the decline succumbed
      to a co-infection of canine distemper virus (CDV) and toxoplasmosis. Sequence
      analysis of the viral P gene, derived by polymerase chain reaction, indicated
      that the virus was closely related to CDV from a mainland USA raccoon (Procyon
      lotor). Nine of 10 foxes trapped in 1999-2000, on the eastern portion of the
      island after the decline, had serologic evidence of exposure to CDV, whereas only
      four of 19 foxes trapped in this region in 1998 had antibodies reactive against
      CDV. The confirmation of CDV in one deceased fox, evidence of exposure to CDV in
      east-end foxes in 1999-2000 compared to 1998, and documentation of raccoon
      introductions to the island, implicates canine distemper as the cause of the
      population decline.

PMID- 19395744
TI  - Ecology of Anaplasma phagocytophilum infection in gray foxes (Urocyon
      cinereoargenteus) in northwestern California.
AB  - Although granulocytic anaplasmosis, caused by infection of Anaplasma
      phagocytophilum, is an emerging human and domestic animal disease, the ecology
      and natural history of the parasite is not well understood. Gray foxes (Urocyon
      cinereoargenteus) are relatively common, occasionally peri-urban mesocarnivores
      whose geographic distribution overlaps the reported distribution of granulocytic
      anaplasmosis in humans and domestic animals in North America. We evaluated the
      potential of foxes as hosts and reservoirs of A. phagocytophilum in both urban
      and backcountry habitats of the Hoopa Valley Indian Reservation, Humboldt County,
      California, USA. We trapped 54 individual foxes and had 16 recaptures for a total
      of 70 fox samples between June 2003 and October 2004 in delineated urban and
      backcountry zones. We collected 296 adult and 145 nymphal ticks from the 70
      captured foxes including 193 Ixodes pacificus, 149 Ixodes texanus, 98 Dermacentor
      variabilis, and one Dermacentor occidentalis. There were seasonal differences in
      tick intensities, with most I. pacificus adults occurring in winter and spring (P
      < 0.001), most I. texanus nymphs in spring (P = 0.03), and most D. variabilis
      adults in spring and summer (P = 0.01). Thirty-six (51%) of the 70 fox sera had
      antibodies against A. phagocytophilum, with a higher (P = 0.24) prevalence in
      backcountry foxes (16 of 23) than in urban-zone foxes (12 of 31). Six (9%) of 70
      fox samples were polymerase chain reaction-positive for A. phagocytophilum.
      Twenty-eight (31%) of 90 domestic dogs sampled from vaccine clinics within the
      study area were seropositive for A. phagocytophilum. There was a significant
      difference in prevalence between dogs and backcountry foxes (70%), but no
      differences were found between dogs and urban foxes (39%). We propose that gray
      foxes are a good sentinel species for A. phagocytophilum infections in
      northwestern California.

PMID- 19395745
TI  - Fishing gear-related injury in California marine wildlife.
AB  - We reviewed medical records from select wildlife rehabilitation facilities in
      California to determine the prevalence of injury in California Brown Pelicans
      (Pelecanus occidentalis), gulls (Larus spp.), and pinniped species (Zalophus
      californianus, Mirounga angustirostris, and Phoca vitulina) due to fishing gear
      entanglement and ingestion from 2001 to 2006. Of 9,668 Brown Pelican, gull, and
      pinniped cases described during the 6-yr study period (2001-06), 1,090 (11.3%)
      were fishing gear-related. Pelican injuries caused by fishing gear were most
      common in the Monterey Bay region, where 59.6% of the pelicans rescued in this
      area and admitted to a rehabilitation center were injured by fishing gear over
      the 6-yr period. The highest prevalence of fishing gear-related injury in gulls
      was documented in the Los Angeles/Orange County region (16.1%), whereas the
      highest prevalences in pinnipeds were seen in the San Diego region (3.7%).
      Despite these higher prevalences of gull and pinniped fishing gear-related
      injuries in these specific regions, there was no statistical significance in
      these trends. Juvenile gulls and pinnipeds were more commonly injured by fishing
      gear than adults (gulls: P = 0.03, odds ratio = 1.29; pinnipeds: P = 0.01, odds
      ratio = 2.07). Male pinnipeds were twice as likely to be injured by fishing gear
      as females (P < 0.01, odds ratio = 2.19). The proportion of fishing gear-related
      injury cases that were successfully rehabilitated and released (percentage of
      cases successfully rehabilitated to the point of release out of the total number
      of fishing gear-related injury cases) was high in all three species groups
      (pelicans: 63%; gulls: 54%; pinnipeds: 70%). Fishing gear-related injuries in
      Brown Pelicans and gulls were highest in the fall, but there was only a
      significant difference between seasons for fishing gear-related injuries in
      pelicans. Fishing gear-related injuries in pinnipeds most commonly occurred in
      summer; however, a statistical difference was not detected between seasons for
      pinnipeds. Derelict fishing gear-lost, abandoned or discarded sport and
      commercial line, nets, traps, etc.-in the marine environment is a significant
      cause of injury in California coastal marine wildlife. We evaluated data for
      stranded animals only; our results may underestimate the true number of coastal
      marine animals injured by lost or discarded fishing gear in California.

PMID- 19395746
TI  - Aerial distribution of ONRAB baits as a tactic to control rabies in raccoons and
      striped skunks in Ontario, Canada.
AB  - During August 2006 and 2007, baits containing oral rabies vaccine, live
      adenovirus vector, known as ONRAB , were aerially distributed in SW Ontario,
      Canada. Bait acceptance during 2006 was 62 and 74% in raccoons (Procyon lotor) in
      areas baited at 150 baits/km(2) and 75 and 77% in plots baited at 300
      baits/km(2). During 2007, bait acceptance for raccoons ranged between 59% and
      80%, and 83% and 87%, in areas baited at 75 and 400 baits/km(2), respectively.
      Bait acceptance by skunks varied among plots (5-24%). Rabies virus-specific
      seroconversion during 2006 averaged 66 and 81% in raccoons in areas baited at 150
      and 300 baits/km(2), respectively. During 2007, seroconversion by raccoons was 76
      and 84% in areas baited at 75 and 400 baits/km(2), respectively. Seroconversion
      by skunks varied among plots (17-51%). Vaccine efficacy, as judged by the
      percentage of animals that consumed a bait and seroconverted, averaged 79 and 87%
      during 2006 for raccoons in areas baited at 150 and 300 baits/km(2),
      respectively, and 81 and 90% in areas baited during 2007 at 75 and 400
      baits/km(2), respectively. Because tetracycline marking was poor in skunks, an
      estimate of vaccine efficacy was not possible. Aerial distribution of ONRAB
      vaccine baits seems to be a feasible tactic for controlling rabies in skunks and
      raccoons.

PMID- 19395747
TI  - Animal rabies in Massachusetts, 1985-2006.
AB  - In this study, we review annual rabies data from Massachusetts from 1985 to 2006,
      spanning the introduction of raccoon strain rabies in 1992. Of 52,034 animals
      tested, 9.7% (5,049/52,034) were rabid, representing 26 of over 67 species
      submitted. Bats were the most common rabid animals prior to 1992 (50 of 52), but
      raccoons (Procyon lotor) became the most common rabies-positive species upon
      arrival of raccoon strain rabies virus (38.2%, 2,728 of 7,138 tested), followed
      by striped skunks (Mephitis mephitis, 34.4%, 1,489 of 4,332), bats (5.3%, 427 of
      8,053), foxes (red fox, Vulpes vulpes, and gray fox, Urocyon cinereoargenteus,
      16.3%, 135 of 827), cats (0.8%, 136 of 18,050), and woodchucks (Marmota monax,
      5.7%, 82 of 1,446). Cats were the most frequently tested animal (34.7%). Raccoon
      strain rabies spread from two foci of introduction with an initial epizootic
      phase of 4 yr, by which time most of the state was affected. In 1992, there was a
      transition from enzootic bat rabies, with little spillover to other animals, to
      terrestrial rabies associated with raccoon strain virus. Although raccoons were
      most affected by the raccoon strain virus, there was spillover to other species,
      particularly to skunks. The eastern United States raccoon rabies epizootic led to
      a marked increase in submissions for rabies testing and the number of positive
      animals detected; however, bat rabies cases remained at their previous levels.
      Wild animal rabies presents a significant threat to humans and domestic/companion
      animals and increased costs related to increased demand for rabies testing,
      postexposure prophylaxis as well as euthanasia of valuable domestic animals.

PMID- 19395748
TI  - Nightly and seasonal movements, seasonal home range, and focal location photo
      monitoring of urban striped skunks (Mephitis mephitis): implications for rabies
      transmission.
AB  - We followed radio-collared striped skunks (Mephitis mephitis) from January 2004
      December 2005 in two urban areas of Flagstaff, Arizona, USA to determine seasonal
      patterns of movement and home-range size. We also used automated cameras to
      determine the potential for inter- and intraspecific interaction at skunks'
      diurnal resting sites and nocturnal focal locations. We found no difference
      between sexes in nightly rates of travel or in size of seasonal home range.
      Nightly rates of travel were greatest in the postbreeding months (May-July) and
      smallest from November to February, consistent with larger home ranges (95%
      kernel estimates) from March-August and smaller home ranges from September
      February. Sixty-three percent of monitored males and 38% of monitored females
      crossed the urban-wildland interface, in at least one direction on at least one
      night, and some remained outside the urban area for days or weeks, indicating
      that skunks could act as vectors of disease across the urban-wildland interface.
      We recorded co-occurrence of skunks with domestic cats (Felis domesticus),
      raccoons (Procyon lotor), gray foxes (Urocyon cinereoargenteus), and other skunks
      at focal locations and diurnal retreats used by skunks, suggesting these areas
      are potential sites for both inter- and intraspecific rabies transmission and
      could be targeted by wildlife managers during trapping or vaccination programs.

PMID- 19395749
TI  - Effects of management, behavior, and scavenging on risk of brucellosis
      transmission in elk of western Wyoming.
AB  - Brucellosis is endemic in elk (Cervus elaphus nelsoni) using winter feedgrounds
      of western Wyoming, USA presumably because of increased animal density, duration
      of attendance, and subsequent contact with aborted fetuses. However, previous
      research addressed antibody prevalence rather than more direct measures of
      transmission and did not account for elk behavior or scavenging in transmission
      risk. Throughout March and early April 2005-07, we monitored 48 sets of culture
      negative, pseudoaborted elk fetuses, placentas, and fluids (fetal units, FUs) on
      one winter free-ranging (WFR) location and four sites (Feedline, High Traffic,
      Low Traffic, Adjacent) associated with four feedgrounds. "At-risk" elk (total elk
      within 5 m of FU) and proportions of elk sniffing and contacting FUs were highest
      on Feedlines and decreased toward Low Traffic sites. We did not observe elk
      investigating FUs Adjacent to feedgrounds or on the WFR location. At-risk elk on
      Feedline and High Traffic sites decreased throughout the sampling period, whereas
      proportions of elk investigating FUs were correlated positively to at-risk elk
      among all sites within feedgrounds. At-risk elk and proportions of elk
      investigating FUs were correlated with total feedground elk density and
      population only on High Traffic and Low Traffic sites. Proportions of sex/age
      groups (female, juvenile, male) investigating FUs did not differ from background
      populations. Females, however, spent more time (mean [SE], 21.07 [3.47] sec)
      investigating FUs than juveniles (14.73 [3.53] sec) and males (10.12 [1.45] sec),
      with positive correlation between total investigations and time spent
      investigating per female. Eight species of scavengers consumed FUs, removing FUs
      faster on feedgrounds than WFR locations and reducing proportions of elk that
      investigated FUs. Our results suggest that 1) reduction of elk density and time
      attending feedgrounds, particularly on Feedlines; and 2) protection of scavengers
      on and adjacent to feedgrounds would likely reduce intraspecific transmission
      risk of brucellosis.

PMID- 19395750
TI  - Population health of Fallow deer (Dama dama) on Little St. Simons Island,
      Georgia, USA.
AB  - Fallow deer (Dama dama) were introduced to Little St. Simons Island, Georgia, USA
      in the 1920s and thrive at high population densities, to the exclusion of white
      tailed deer (Odocoileus virginina). The presence of introduced pathogens and
      parasites as a result of their introduction is currently unknown, as is the
      impact of native disease on the exotic fallow deer. Hunter-killed fallow deer
      from 2003-2005 were necropsied and surveyed for evidence of infectious disease,
      parasitic agents, and toxicologic parameters. Fallow deer were positive for
      antibodies to bovine virus diarrhea virus I and II, bluetongue virus, and bovine
      adenovirus. Twenty species of bacteria were isolated from the internal organs,
      and 14 species of parasites were recovered including one abomasal nematode,
      Spiculopteragia asymmetrica, which is not known to occur in native North American
      ungulates. Concentrations of liver and copper were low, while lead, zinc, and
      iron were considered within normal levels. No clinical signs of disease were
      noted, and the overall health of the insular fallow deer was considered good.

PMID- 19395751
TI  - Feral swine contact with domestic swine: a serologic survey and assessment of
      potential for disease transmission.
AB  - Feral swine (Sus scrofa) are present in 38 of the 50 United States, and their
      populations continue to expand. Domestic swine are widely regarded as vulnerable
      to diseases harbored by feral swine. Our objectives were to determine antibody
      prevalence for selected pathogens in Texas feral swine populations and identify
      contact events between feral and domestic swine. Overall prevalence of antibodies
      against brucellosis and pseudorabies virus was 11% and 30%, respectively.
      Antibodies to porcine reproductive and respiratory disease virus were detected in
      3% of feral swine from southern Texas. All samples tested negative for antibodies
      to classical swine fever virus. To determine the frequency of contact events
      between feral swine and domestic swine in neighboring facilities, we analyzed
      movement data from 37 adult feral swine that were trapped < or =10 km from
      domestic swine facilities and equipped with geographic positioning system
      collars. Seven of the 37 feral swine had contact (relocated within 100 m) with
      domestic swine. We found that contact between feral swine and domestic swine
      occurred predominantly at night. Additionally, we analyzed 60 consecutive days of
      experimental track plots around pens that contained domestic swine and empty
      control pens, and found greater visitation by feral swine to the domestic swine
      pens. Our data demonstrate that feral swine have direct contact with domestic
      swine, which presents opportunity for disease transmission.

PMID- 19395752
TI  - Seasonal variation in Sin Nombre virus infections in deer mice: preliminary
      results.
AB  - The proportion of deer mice (Peromyscus maniculatus) with recently acquired Sin
      Nombre virus (SNV) infections is an indicator of epizootic intensity and may be
      key in predicting outbreaks of hantavirus cardio-pulmonary syndrome in humans. We
      investigated whether incidence of recent infections was related to season, sex,
      reproductive status, or habitat disturbance. In May and September, 2006, we
      sampled 912 deer mice at six sites in Utah. We determined SNV antibody prevalence
      and estimated the number of recent infections with an avidity enzyme-linked
      immunosorbent assay. Antibody prevalence in adults (n = 735) was 22%, and
      putative maternal antibody prevalence in juveniles (n = 177) was 7%. Sampling
      period explained a significant amount of the variance in the probability of
      recent infections, which were two times more common in May versus September.
      Additionally, prevalence of high-avidity maternal antibodies (i.e., from dams
      with older infections) in juveniles did not correspond to the antibody avidity
      patterns in adult females. In May, no juveniles had high-avidity antibodies
      compared to adult females (49%); in September, avidity could not be measured in
      juveniles because none were seropositive, despite large sample sizes (n = 84) and
      an 11% seroprevalence in adult females. Based on the results, coupled with those
      from the literature, we speculate that the majority of new infections may occur
      predominantly in the spring and that SNV may impair reproductive output of
      females.

PMID- 19395753
TI  - Ticks and tick-borne pathogens from wildlife in the Free State Province, South
      Africa.
AB  - Eight ixodid tick species, associated with 59 free-ranging mammals belonging to
      10 species, were collected at five different localities in the Free State
      Province, South Africa. Four of the study areas were nature reserves (Willem
      Pretorius, Sandveld, Tussen-die-Riviere, and Soetdoring), and one site was a
      private farm located in Senekal district. The collection was performed from March
      2006 until June 2006. Ticks (n=569) and tissues from animals (n=52) were analyzed
      by polymerase chain reaction, reverse line blot, and sequencing for various tick
      borne pathogens belonging to the genera Babesia, Theileria, Anaplasma, and
      Ehrlichia. Rhipicephalus (Boophilus) microplus, the known vector of Babesia bovis
      responsible for Asiatic redwater in South Africa, was found for the first time in
      the Free State Province. Rhipicephalus warburtoni [corrected] also was collected
      in areas in the Free State where it has not been previously described. Anaplasma
      marginale was detected for the first time in a gemsbok (Oryx gazella gazella).
      Gene sequences recovered in this study were 98-100% homologous with GenBank
      sequences for Anaplasma bovis, Theileria separata, and Theileria sp. Malelane
      sable antelope.

PMID- 19395754
TI  - Diagnostic testing patterns of Renibacterium salmoninarum in spawning salmonid
      stocks in Michigan.
AB  - Bacterial kidney disease (BKD), caused by Renibacterium salmoninarum, is a slowly
      progressing disease that threatens salmon conservation and restoration programs
      in North America. The purpose of this study was to track naturally occurring R.
      salmoninarum infection in representative, Michigan, USA, salmonid stocks using
      nested polymerase chain reaction (nPCR), quantitative enzyme-linked immunosorbent
      assay (Q-ELISA), and culture. The Q-ELISA test detected 67.6% infection
      prevalence, which is lower than culture (77.2%) or nPCR (94.2%), yet it provided
      semiquantitative data on infection intensity. The disagreement in results among
      the three assays may reflect the different phases of R. salmoninarum infection at
      the time of sampling. The testing results demonstrated the presence of six
      patterns, with each of the patterns representing a probable stage along the
      course of natural R. salmoninarum infection. Findings also suggest that fish
      stocks tested in this study were not uniform in the distribution of the
      diagnostic patterns and that, from studying such patterns, one can determine the
      course of BKD infection in a particular population.

PMID- 19395755
TI  - Butorphanol-azaperone-medetomidine for immobilization of captive white-tailed
      deer.
AB  - Drug combinations are commonly used to immobilize white-tailed deer (Odocoileus
      virginianus) for capture or handling. Although efficacy of various compatible and
      complementary drugs has been tested in clinical trials with deer, extensive
      negative side effects, impractical drug volume, and slow recovery from
      immobilization sometimes make these combinations less than ideal for routine
      field use. We hypothesized that a combination of butorphanol, azaperone, and
      medetomidine (BAM) would provide safe and effective immobilization of captive
      white-tailed deer while minimizing these complicating factors. We tested two
      dosages of this drug combination (BAM-1 and BAM-2) and two dosages of a
      naltrexone, tolazoline, and atipamezole antagonist combination (NTA-1 and NTA-2)
      with captive white-tailed deer. We characterized efficacy of drug for
      immobilization, quality of drug induction, and recovery after drug reversal, and
      we compared our findings with those of previous drug trials. Complete
      immobilization and excellent induction quality was achieved with a low volume
      dosage of BAM-2. Time to drug induction and deer recumbency for BAM-2 compared
      favorably with results from previous trials involving xylaxine/ ketamine and
      medetomidine/ketamine but without risk of hyperthermia. We found no differences
      in time to deer recovery for NTA-1 and NTA-2, with deer treated with either
      combination standing by 30 min postinjection. Regardless of immobilizing drugs
      used, we suggest practitioners monitor for signs of circulatory deficiency in
      deer and provide supplemental oxygen when needed.

PMID- 19395756
TI  - Butorphanol, azaperone, and medetomidine anesthesia in free-ranging white-tailed
      deer (Odocoileus virginianus) using radiotransmitter darts.
AB  - Fourteen free-ranging white-tailed deer (Odocoileus virginianus) were
      successfully anesthetized for a total of 15 anesthetic events using a combination
      of butorphanol (mean+/-SD, 0.58+/-0.1 mg/kg), azaperone (0.37+/-0.06 mg/kg), and
      medetomidine (0.19+/-0.03 mg/kg) (BAM) administered by radiotelemetry darts from
      hunting blinds between November 2006 and May 2007. Mean time to locate deer
      (mean+/-SD, 17. 3+/-7 min), to recumbency (21.4+/-5 min), to initiation of data
      acquisition (27.5+/-8 min), total down time (37+/-6 min), and average distance
      run (161+/-82 m) were recorded. Physiologic monitoring was done every 5 min for a
      total of 20 min. Arterial blood gases were collected every 10 min. Mild to
      moderate hypoxemia and mildly depressed ventilation occurred in some animals.
      Muscle relaxation and plane of anesthesia were adequate for completion of all
      procedures; two deer were administered intravenous butorphanol supplementation to
      achieve light anesthesia (mean+/-SD, 0.19 mg/kg; 0.12 mg/kg). Recovery following
      intramuscular administration of naltrexone (1.34+/-0.42 mg/kg; 2x butorphanol
      dose) and atipamezole (0.93+/-0.14 mg/kg; 5x medetomidine dose) was rapid,
      smooth, and complete. Mean+/-SD recovery time was 4.5+/-1.5 min. Overall efficacy
      of the Pneu-Dart radiotelemetry system was 65%. Negative attributes of this
      protocol included long induction time and dart failure. No known mortalities
      occurred as a result of the study. This drug combination provided safe, reliable,
      short-term anesthesia of free-ranging white-tailed deer. Further evaluation for
      use in field procedures in other cervids is warranted.

PMID- 19395757
TI  - An assessment of injury to European badgers (meles meles) due to capture in
      stopped restraints.
AB  - As part of ongoing culling operations, European badgers (Meles meles) were
      captured using stopped restraints in winter (October to December 2005) and summer
      (May to June 2006) in the Republic of Ireland. A subset of these badgers, those
      caught during four consecutive nights, was examined postmortem to determine the
      frequency and severity of physical injuries resulting from capture in the
      restraints. The skin and the tissues underlying the restraint of 343 badgers were
      assessed for injury by visual examination. There was an absence of skin damage or
      only minor skin abrasions in 88% of badgers; an absence of subcutaneous tissue
      injury or only localized subcutaneous tissue injury in 69%; and an absence of
      muscle injury or only slight muscle bruising in 99% of badgers. Only 2% of
      badgers had cuts to the skin and 5.5% had extensive subcutaneous edema, whereas
      1.2% had areas of hemorrhage and tearing of the underlying muscle. Our results
      show that the majority of badgers examined sustained minimal injuries
      attributable to capture in stopped restraints.

PMID- 19395758
TI  - Hematologic and biochemistry reference values for the endangered riparian brush
      rabbit (Sylvilagus bachmani riparius).
AB  - The objective of this study was to establish reference hematologic and
      biochemistry values for adult riparian brush rabbits (Sylvilagus bachmani
      riparius). Between February 2002 and December 2003, complete blood cell counts
      and serum biochemistry panels were done on blood samples collected for 252
      healthy, adult riparian brush rabbits that were bred in captivity and released to
      the wild in the California, USA, San Joaquin Valley. Significant differences in
      mean values of some analytes were found among males, nonpregnant females, and
      pregnant females and among seasons. However, when reference values for each
      subgroup (sex, pregnancy status, and season) were compared with reference values
      for all riparian rabbits combined, differences were not sufficiently relevant
      clinically to warrant the adoption of separate subgroup-specific reference
      values. The reference ranges reported herein will be of value to veterinarians
      and wildlife biologists assessing the health of riparian brush rabbits and other
      wild Sylvilagus species.

PMID- 19395759
TI  - Knemidokoptic mange in Hawai'i' Amakihi (Hemignathus virens) on the island of
      Hawai'i.
AB  - Lesions resembling knemidokoptic mange on the feet and tarsometatarsi of two
      Hawai'i' Amakihi (Hemignathus virens) were observed while the researchers were
      mist-netting wild passerines at Manuka Natural Area Reserve on the island of
      Hawai'i between 14 June 2007 and 19 June 2007. During subsequent mist-netting
      from September 2007 through February 2008, we found 26% (7/27) of the Hawai'i'
      Amakihi caught were similarly affected. Microscopic examination of skin scrapings
      from lesions of affected individuals revealed Knemidokoptes jamaicensis (Acari:
      Knemidokoptidae). This is the first report of Knemidokoptes spp. found in wild
      passerines in Hawai'i. No other wild passerines (n=573) have been found with
      knemidokoptic mange during our islandwide study of Hawai'i' Amakihi.

PMID- 19395760
TI  - Clinical demodicosis in African buffalo (Syncerus caffer) in the Kruger National
      Park.
AB  - We investigated the relationship between prevalence and severity of clinical
      signs of Demodex cafferi infection in free-ranging African buffalo (Syncerus
      caffer) and other factors such as age, sex, pregnancy status, and concomitant
      infections with bovine tuberculosis (BTB), Rift Valley fever (RVF), and
      brucellosis (BA). Approximately half of 203 buffalo examined in this study had
      clinical signs of demodicosis (cutaneous nodules); younger age classes had the
      highest prevalence and severity of lesions (chi(2)=21.4, df=6, P=0.0015). Nodules
      were generally limited to the head and neck region, but in severe cases were
      present over the entire animal. We found no significant association between
      clinical severity of the Demodex infection and gender, pregnancy status, or
      infection with BTB, RVF, or BA.

PMID- 19395761
TI  - Dermoid cysts in caribou.
AB  - Subcutaneous dermoid cysts were identified in eight wild caribou (Rangifer
      tarandus) from widely dispersed locations in northern Canada and in one wild
      caribou from Alaska. The dermoid cysts from Canadian caribou were found among 557
      diagnostic specimens that had been detected by hunters and submitted by resource
      officers and biologists between 1 January 1966 and 15 May 2007. All of the cysts
      were located in the cervical region, and five of nine cysts were found in the
      throat area. All of the animals for which the age was known were adult; males and
      females were equally represented. Dermoid cysts were not diagnosed in any of
      1,108 white-tailed deer (Odocoileus virginianus), 293 mule deer (Odocoileus
      hemionus), 174 elk (Cervus elaphus), or 529 moose (Alces alces) examined during
      the same period at the Canadian laboratory.

PMID- 19395762
TI  - Investigation of the role of Austrian ruminant wildlife in the epidemiology of
      malignant catarrhal fever viruses.
AB  - Malignant catarrhal fever (MCF) is an ubiquitous disease of cattle and other
      ruminants caused by Ovine herpesvirus 2 (OvHV-2), which is endemic in sheep and
      transmitted from healthy carriers. Further viruses of the MCF group are also able
      to induce MCF in ruminants. As alpine pasturing is very common in Austria,
      possible contact with ruminant wildlife carrying and excreting MCF viruses might
      be suspected as an infection source. To investigate the epidemiologic role of
      Austrian deer and chamois, spleen samples were collected from 55 red deer (Cervus
      elaphus), 72 roe deer (Capreolus capreolus), four fallow deer (Dama dama), and
      five chamois (Rupicapra rupicapra) during the hunting seasons 2001-2003. Samples
      were tested by both herpesvirus consensus and OvHV-2-specific polymerase chain
      reaction. As all spleen samples tested negative, there is no indication that in
      the region and period investigated, MCF viruses circulated in wild ruminants.

PMID- 19395763
TI  - Active surveillance for avian influenza virus infection in wild birds by analysis
      of avian fecal samples from the environment.
AB  - A total of 1991 environmental samples of fresh avian feces and urine from several
      aquatic bird species in a coastal area of Northeast Germany were examined for the
      presence of avian influenza viruses (AIV). By real-time reverse-transcriptase
      polymerase chain reaction, specific for an M gene of influenza A viruses, none of
      659 duck samples and only 11 (0.9%) of 1,268 geese and swan samples tested
      positive. Two of these were identified as H5N2 viruses of low pathogenicity.
      Conventional cloacal and oropharyngeal swab samples (n=1,402) collected in an
      adjacent coastal region in Northeast Germany from comparable species of captured
      or hunted birds, yielded a similar detection rate (3/901; 0.4%) for AIV-specific
      RNA in geese and swans, but a higher rate (4/309; 1%) for ducks. No virus
      isolates were obtained from either set of samples. Collection of environmental
      avian samples was simple and cost effective and also allowed us to regulate
      sample sizes over time. A species assignment of these samples was possible,
      provided that close presampling observation of birds at the sampling sites was
      secured. Environmental sampling to monitor AIV in wild bird populations may be a
      valid alternative to the more-invasive and capture-dependent methods based on
      cloacal sampling.

PMID- 19395764
TI  - Serologic evidence of influenza A and B viruses in South American fur seals
      (Arctocephalus australis).
AB  - The aim of this work was to detect serologic evidence of influenza virus
      infections in South American fur seals (Arctocephalus australis) that inhabit the
      Uruguayan coast. In 29 of 37 serum samples that were analyzed, we identified
      antibodies to at least one of the following antigens: H1N1
      (A/NewCaledonia/20/99), B/Beijing/184/93-like viruses, B/Hong Kong/330/01, and
      B/Sichuan/379/99 by means of the hemagglutination inhibition assay (HAI). Results
      confirmed that influenza A viruses circulate in marine mammals and also showed,
      for the first time, indirect evidence of influenza B infections in Arctocephalus
      australis.

PMID- 19395765
TI  - Encephalomyocarditis virus infection in wildlife species in Greece.
AB  - The objective of this work was to search for potential wildlife reservoir hosts
      of Encephalomyocarditis virus (EMCV) in wildlife species. From 1994 to 2006, 317
      blood and tissue samples were collected from 17 wildlife species in Greece.
      Encephalomyocarditis virus was isolated only from two Rattus rattus. In addition,
      antibody to EMCV were detected in sera from 39 Rattus rattus, one Apodemus
      sylvaticus, one Microtus arvalis, and 13 Sus scrofa.

PMID- 19395766
TI  - Canine distemper virus in a crab-eating fox (Cerdocyon thous) in Brazil: case
      report and phylogenetic analyses.
AB  - Although canine distemper is enzootic worldwide and has a wide host range, there
      are no reports of canine distemper virus in crab-eating foxes (Cerdocyon thous)
      that provide information on virus phylogeny and histopathologic lesions. The
      objective of this study is report and describe canine distemper in a crab-eating
      fox (C. thous), with a focus on the phylogeny of the virus strain and the
      histopathologic lesions in the animal.

PMID- 19395767
TI  - Serologic survey for selected infectious diseases in raccoons (Procyon lotor) in
      Indiana, USA.
AB  - The objective of this study was to characterize the antibody prevalence of
      important livestock and domestic animal pathogens in raccoons (Procyon lotor)
      trapped and sampled in 39 forest patches in north-central Indiana, USA, between
      2004 and 2005. A total of 459 serum samples were tested for antibodies to
      Leptospira serovars, 512 for Canine distemper virus (CDV) antibodies, and 340 for
      antibodies to Porcine reproductive and respiratory syndrome virus (PRRSV). In
      total, 47, 16, and 0% of the samples were seropositive for at least one
      Leptospira serovar, CDV, and PRRSV, respectively. Most of the positive Leptospira
      results were to serovars grippotyphosa (36%), autumnalis (22%), and hardjo (22%).
      No statistically significant correlation was found between antibody prevalence
      estimates for different Leptospira serovars. A significant association was found
      between body weight and antibodies for Leptospira serovars and CDV. In addition,
      age (adult vs. juvenile) was significantly associated with the presence of CDV
      antibody, with adults exhibiting a higher prevalence than juveniles. This study
      confirmed that raccoons in Indiana, USA, are exposed to different Leptospira
      interrogans serovars and CDV and that age and weight are associated with the
      presence of antibodies for both pathogens.

PMID- 19395768
TI  - Lack of evidence for the drought-linked chytridiomycosis hypothesis.
AB  - A significant amount of recent research has focused on the potentially
      synergistic roles of climate change and disease in causing amphibian declines and
      extinctions. Herein I discuss the drought-linked chytridiomycosis hypothesis
      (DLCH), which states that prolonged or intensified dry seasons trigger or
      exacerbate epidemics of chytridiomycosis, a potentially lethal skin disease of
      amphibians caused by the chytrid fungus Batrachochytrium dendrobatidis. I
      demonstrate that the DLCH runs contrary to our knowledge of B. dendrobatidis
      physiology, biogeography, and host-parasite ecology and conclude that abnormally
      dry weather should actually favor amphibians by decreasing the prevalence,
      severity, and spread of chytridiomycosis.

PMID- 19395769
TI  - Non-invasive body temperature measurement of wild chimpanzees using fecal
      temperature decline.
AB  - New methods are required to increase our understanding of pathologic processes in
      wild mammals. We developed a noninvasive field method to estimate the body
      temperature of wild living chimpanzees habituated to humans, based on
      statistically fitting temperature decline of feces after defecation. The method
      was established with the use of control measures of human rectal temperature and
      subsequent changes in fecal temperature over time. The method was then applied to
      temperature data collected from wild chimpanzee feces. In humans, we found good
      correspondence between the temperature estimated by the method and the actual
      rectal temperature that was measured (maximum deviation 0.22 C). The method was
      successfully applied and the average estimated temperature of the chimpanzees was
      37.2 C. This simple-to-use field method reliably estimates the body temperature
      of wild chimpanzees and probably also other large mammals.

PMID- 19395770
TI  - Allometric scaling of chemical restraint associated with inhalant anesthesia in
      giant anteaters.
AB  - This study describes the use of allometric scaling in five giant anteaters
      (Myrmecophaga tridactyla) submitted for osteosynthesis, gastrostomy, or treatment
      of burns. Chemical restraint was performed by allometric scaling using the dog as
      a reference; acepromazine (0.06 mg/kg), diazepam (0.3 mg/kg), ketamine (8.8
      mg/kg), and buprenorphine (5.9 microg/kg) were combined, and the animals were
      maintained under isoflurane anesthesia. Heart rate, respiratory rate, hemoglobin
      oxygen saturation, temperature, and anesthetic depth were measured. Postoperative
      treatment consisted of ketoprofen, buprenorphine, and ceftiofur. Anesthetic
      induction was obtained in 10-15 min, achieving muscle relaxation and absence of
      excitement. Physiologic parameters were stable during the procedures, and
      postoperative treatment was effective. Allometric scaling was effective for
      chemical restraint and postoperative treatment.

PMID- 19395772
TI  - Decomposition of charge-state distributions for a better understanding of
      electrospray mass spectra of bioorganic compounds. Part 1: basic formalism.
AB  - Further development in our approach for the interpretation of a mass spectral
      peak series resulting from unique modifications at a number of molecular sites is
      described and its application for the analysis of electrospray mass spectra of
      multiply-charged ions of biopolymers is specified. This method was based
      initially on the assumption that the modifications are mutually independent. The
      output is a set of modification probabilities for the considered molecular sites,
      which explains the observed peak intensity distribution with the best accuracy.
      It is shown here that the method is also applicable, in some cases, to the strong
      interaction between modified sites. This is important for the formation of
      multiply-charged ions, at least in the gas phase, since it should be
      significantly influenced by the internal electric fields. The capabilities and
      limitations of this approach are discussed. One limitation is that only unimodal
      distributions (those having only one maximum) are possible in the considered
      model. Another is that relatively large biomolecules may not be suitable for this
      type of analysis. Some experimental results of the application of this method are
      described in Part 2 of this work.

PMID- 19395773
TI  - Decomposition of charge-state distributions for better understanding of
      electrospray mass spectra of bioorganic compounds. Part 2: application of the
      method.
AB  - The results of the analysis of electrospray mass spectra of b-endorphin and
      chicken egg lysozyme in different conditions of data acquisition using the method
      described in Part 1 of the work are reported. At least partial unfolding during
      the process of ion formation in the electrospray ion source of an initially
      native biomolecule of lyzozyme in solution should supposedly explain the received
      set of probabilities of proton retention by basic and acidic residues of this
      molecule for all considered conditions of data acquisition.

PMID- 19395774
TI  - Cyclization of 2-acyl- and 2-thioacylaminobenzylcyclopropanes in the gas phase
      and solution.
AB  - Mass spectrometry proved itself to be a powerful tool to predict the directions
      and yields of mono- molecular reactions of organic compounds. Electron ionization
      (EI) and electrospray ionization (ESI) were used to study possible
      transformations of N-(ortho-cyclopropylmethylphenyl)arylamides I and N-(ortho-
      cyclopropylmethylphenyl)arylthioamides II as well as their para-isomers III and
      IV in a mass spectrometer and to predict directions and yields of their acid
      catalyzed cyclization reactions. Several five-eight-membered heterocycles were
      proposed as possible products of intramolecular transformations of compounds I
      and II. Reactions of compounds I and II in sulfuric acid solutions were carried
      out and the results obtained were compared with mass spectrometric data.
      Surprisingly, EI of the studied compounds mimics their solution reactions better
      than ESI.

PMID- 19395775
TI  - Quantification of oligonucleotide containing sequence failure product: comparison
      of isotope dilution mass spectrometry with other quantification methods.
AB  - There is an increasing demand to develop a method for accurate quantification of
      DNA. Because current methods such as the ultraviolet (UV) absorption-based method
      are only capable of relative quantification, the quantification result depends
      completely on the reference material. To achieve accurate quantification of DNA,
      we have performed isotope dilution mass spectrometry (ID MS)-based quantification
      of oligonucleotides. We chose a 20-mer synthetic oligonucleotide as the analyte
      with a longer sequence failure product. Oligonucleotides sometimes contain
      sequence failure products, which are difficult to remove. It is important to
      quantify a target product in such mixture. After evaluating the content of the
      sequence failure product, the analyte spiked with stable isotopically labeled
      deoxynucleotide monophosphates (dNMPs) was digested by enzyme to its constituent
      dNMPs or deoxynucleosides, and quantified by liquid chromatography-mass
      spectrometry. The obtained mass fractions of the 20-mer oligonucleotide showed a
      good agreement with the results based on phosphate analysis by inductively
      coupled plasma-optical emission spectrometry and ion chromatography. UV
      absorption, the general method for DNA quantification, resulted in
      underestimation. On the other hand, the mass fraction obtained by the gravimetric
      method was overestimated. This study shows that the ID MS method can determine
      the precise mass fraction of the target oligonucleotide with the sequence failure
      product and possesses potential as the primary method for the certification of
      DNA as a reference material.

PMID- 19395776
TI  - Solvation in gas-phase reactions of sulfonic group containing ionic liquids in
      electrospray ionization quadrupole ion trap mass spectrometry.
AB  - In electrospray ionization (ESI) quadrupole ion trap mass spectrometry, certain
      fragment ions generated in the ion trap from a series of sulfonic group
      containing ionic liquids (ILs) are found to undergo ion-molecule reactions with
      ESI solvent molecules (water, acetonitrile and methanol) to form adduct species.
      These unexpected solvated fragment ions severely complicate the interpretation of
      mass spectrometric data. Multi-stage fragmentation mass spectra were used to
      ascertain the chemical structures of these adduct species. It is important that
      solvation must be taken into account in order to prevent erroneous data
      interpretation for sulfonic group containing ILs.

PMID- 19395777
TI  - Analysis of caffeic acid derivatives from Osmanthus yunnanensis using
      electrospray ionization quadrupole time-of-flight mass spectrometry.
AB  - A series of six caffeic acid derivatives (1-6) in Osmanthus yunnanensis were
      investigated by electrospray quadrupole time-of-flight tandem mass spectrometry
      (ESI-QToF-MS/MS) in both negative- and positive-ion modes. High-quality MS/MS
      spectra of [M + H](+) are generated from high-abundance protonated parent ions
      obtained by addition of ammonium chloride to the solutions. Fragmentation
      mechanisms of [M - H](-) and [M + H](+) precursor ions were proposed and
      elemental compositions of most of the product ions were confirmed on the basis of
      the high-resolution ESI-collision-induced dissociation (CID)- MS/MS spectra. It
      was found that the fragment ions at m/z 179, m/z 161, m/z 135 and m/z 134 in
      negative-ion mode and at m/z 163, m/z 145 and m/z 135 in positive mode should be
      the characteristic ions of caffeic acid. In addition, the radical fragment ions
      with high abundance were observed for many caffeic acid derivatives especially
      for 4. The structural elements of unknown compounds 7 and 8 were tentatively
      identified on based on tandem mass spectra of known ones.

PMID- 19395778
TI  - Metastable processes investigated on an orthogonal-axis time-of-flight
      instrument: mass-scale calibration and application.
AB  - In this letter, the authors would like to present a rapid method for mass-scale
      calibration of metastable dissociation in an orthogonalaxis time-of-flight
      instrument. The calibrating ion is a protonated polyhedral oligomeric
      silsesquioxane (POSS) generated in electrospray ionization. In addition,
      dissociation mechanisms for protonated POSS are proposed. Finally, the interest
      of the method is illustrated in the context of a collision-induced dissociation
      investigation of sodium-cationized polylactide.

PMID- 19395779
TI  - Beta-methylamino-L-alanine analysis by liquid chromatography tandem mass
      spectrometry with iTRAQ as the derivative.
AB  - Amino acid BMMA is produced by cyanobacteria and has been linked to the
      development of neurodegenerative diseases. We developed a method for quantitative
      analysis of BMAA in biological samples and plant extracts. The method is
      utilizing iTRAQ and LC-MS/MS detection using multiple reaction monitoring mode.
      The method uses 50 microL of sample and has a limit of quantitation of 300 ng mL(
      1), within-run run imprecision below 1%. Using this method we analyzed human
      serum samples, human cerebrospinal fluid samples and extract of the cycad seed.
      No BMAA could be detected in the human samples. Content of BMAA in the seed was
      50 mg kg(-1).

PMID- 19395780
TI  - Cardiorenal syndrome.
AB  - Very often, physicians confront with patients who have concomitant heart and
      kidney failure. The coexistence of kidney and heart failure carries an extremely
      bad prognosis. The exact cause of deterioration of kidney function and the
      mechanism underlying this interaction are complex, multifactorial in nature, and
      still not completely understood. Both the heart and the kidney act in tandem to
      regulate blood pressure, vascular tone, diuresis, natriuresis, etc. An extension
      to the Guytonian model of volume and blood pressure control is proposed called
      cardiorenal connection. Regulating actions of Guyton's model were coupled to
      their extended actions on structure and function of the heart and the kidney
      changes in the rennin-angiotensin-aldosterone system, the imbalance between
      nitric oxide and reactive oxygen species, the sympathetic nervous system, and
      inflammation are the cardiorenal connectors to develop cardiorenal syndrome.
      Imbalance in this closed complex will often lead to deterioration of both cardiac
      and kidney function. The World Congress of Nephrology emphasized vast
      interrelated derangements that can occur in cardiorenal syndrome and proposed
      that the recent definition of cardiorenal syndrome be modified into categories
      whose labels reflect the likely primary and secondary pathology and time frame.
      For management, drugs that impair kidney function are undesirable, particularly
      in a population with already compromised or at risk of kidney function. In severe
      volume-loaded patients who are refractory to diuretics, management of cardiorenal
      dysfunction is challenging. In the absence of definitive clinical trials,
      treatment decision must be based on a combination of patient's condition and
      understanding of individual treatment options.

PMID- 19395781
TI  - Hypercalcemia: an evidence-based approach to clinical cases.
AB  - Primary hyperparathyroidism and malignancy are responsible for greater than 90%
      of all cases of hypercalcemia. Compared with the hypercalcemia of malignancy,
      hyperparathyroidism tends to be associated with lower serum calcium levels (< 12
      mg/dL) and a longer duration of hypercalcemia (more than 6 months). The
      hypercalcemic symptoms are usually fewer and subtle. Hyperparathyroidism tends to
      cause kidney calculi, hyperchloremic metabolic acidosis, and the characteristics
      of metabolic bone disease osteitis fibrosa cystica, but no anemia. In contrast,
      hypercalcemia of malignancy is typically rapid in onset, with higher serum
      calcium levels, and more severe symptoms. Patients so affected show marked
      anemia, but they never have kidney calculi or metabolic acidosis. Parathyroid
      hormone assay is the most useful test for differentiating hyperparathyroidism
      from malignancy and other causes of hypercalcemia. In hyperparathyroidism, serum
      parathyroid hormone levels will be elevated. In other cases, the high serum
      calcium concentration usually results in suppression of parathyroid hormone.
      Treatment of hypercalcemia should be started with hydration. Loop diuretics may
      be required in individuals with renal insufficiency or heart failure to prevent
      fluid overload. Calcitonin is administered for the immediate short-term
      management of severe symptomatic hypercalcemia. For long-term control of severe
      or symptomatic hypercalcemia, the addition of biphosphonate is typically
      required. Among intravenous bisphosphonates, zoledronic acid or pamidronate are
      the agents of choice. Glucocorticoids are effective in hypercalcemia due to
      lymphoma or granulomatous diseases. Dialysis is generally reserved for those with
      severe hypercalcemia complicated with kidney failure.

PMID- 19395782
TI  - Renoprotective activity of benincasa cerifera fruit extract on
      ischemia/reperfusion-induced renal damage in rat.
AB  - INTRODUCTION: Evidence suggests that reactive oxygen species play a role in the
      pathophysiology of renal ischemia/reperfusion (I/R) injury. This study was
      designed to investigate the renoprotective activity of methanolic fruit extract
      of Benincasa cerifera in I/R-induced kidney failure in rats. MATERIALS AND
      METHODS: Renal pedicles of 12 rats were occluded for 60 minutes followed by 24
      hours of reperfusion. Six days prior to induction of I/R, 6 of the rats received
      Benincasa cerifera, 500 mg/kg, orally. Serum creatinine, urea, and uric acid
      levels were measured after the operation. At the end of reperfusion period, the
      rats were sacrificed. Superoxide dismutage, catalase, reduced glutathione, and
      renal malondialdehyde content were determined in the renal tissues. Results were
      compared with a group of rats with sham operation. RESULTS: Renal I/R caused
      significant impairment of kidney function. Six-day administration of Benincasa
      cerifera, however, minimized this effect. Rats with renal I/R only showed
      significantly decreased activity of superoxide dismutage, catalase, and reduced
      glutathione compared with the sham-operated rats. These declining trends were
      significantly less in the group treated with Benincasa cerifera compared with
      those in the I/R-only group (P = .008, P = .07, and P < .001, respectively).
      Renal I/R produced a significant increase in malondialdehyde level, while
      pretreatment with Benincasa cerifera was associated with a significantly lower
      malondialdehyde level (P < .001). CONCLUSIONS: These findings imply that reactive
      oxygen species play a crucial role in I/R-induced kidney injury and Benincasa
      cerifera exerts renoprotective activity probably by the radical scavenging
      activity.

PMID- 19395783
TI  - Urinary sodium and potassium excretion following karate competitions.
AB  - INTRODUCTION: Exercise induces renal hemodynamic alterations and stimulates
      electrolytes excretion. The purpose of this study was to assess urinary excretion
      of sodium and potassium in karate practitioners, following competitions.
      MATERIALS AND METHODS: The study population composed of 18 healthy men, aged 18
      to 21 years, with similar physical characteristics. They were professional
      karatekas with a history of at least 7 years of karate training. The participants
      competed in 3 rounds of about 3 minutes in duration with 10 minutes resting
      intervals between them. The 24-hour urine samples were collected before (while
      trainings were stopped) and after the match and their sodium and potassium
      concentrations were measured. Also, blood samples were obtained before and after
      the match for measurement of these electrolytes in the participants' sera.
      RESULTS: Before the match, the mean values of urinary sodium and potassium were
      200.3 +/- 89.3 mEq/L/d and 68.5 +/- 12.9 mEq/L/d, respectively. After the match,
      they changed into 206.9 +/- 74.7 mEq/L/d and 67.1 +/- 14.4 mEq/L/d, respectively.
      No significant alterations were observed in urinary sodium and potassium
      excretion following karate match (P = .94 and P = .96, respectively). Serum
      sodium levels were 136.7 +/- 3.1 mEq/L and 136.3 +/- 2.9 mEq/L, before and after
      the match, respectively (P = .11), serum potassium levels were 4.2 +/- 0.3 mEq/L
      and 4.1 +/- 0.2 mEq/L, respectively (P = .16). CONCLUSIONS: With regard to short
      duration and anaerobic nature of karate, it seems that a Karate match does not
      contribute to excessive urinary electrolytes excretion.

PMID- 19395784
TI  - Diagnostic potential of urinary tumor necrosis factor-alpha in children with
      acute pyelonephritis.
AB  - INTRODUCTION: Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of
      the inflammatory response in serious bacterial infections. The aim of this study
      was to evaluate the potential of urinary TNF-alpha for diagnosis of acute
      pyelonephritis in children. MATERIALS AND METHODS: This study was conducted from
      March 2006 to December 2007 on children with confirmed diagnosis of acute
      pyelonephritis. They all had positive renal scintigraphy scans for pyelonephritis
      and leukocyturia. The ratios of urinary TNF-alpha to urine creatinine level were
      determined and compared in patients before and after antibiotic therapy. RESULTS:
      Eighty-two children (13 boys and 69 girls) with acute pyelonephritis were
      evaluated. The mean pretreatment ratio of urinary TNF-alpha to urinary creatinine
      level was higher than that 3 days after starting on empirical treatment (P =
      .03). The sensitivity of this parameter was 91% for diagnosis of acute
      pyelonephritis when compared with demercaptosuccinic acid renal scintigraphy as
      gold standard. CONCLUSIONS: Based on our findings in children, the level of
      urinary TNF-alpha-creatinine ratio is acute increased in pyelonephritis and it
      decreases after appropriate therapy with a high sensitivity for early diagnosis
      of the disease. Further research is warranted for shedding light on the potential
      diagnostic role of urinary TNF-alpha in pyelonephritis in children.

PMID- 19395785
TI  - C-reactive protein level following treatment and withdrawal of lovastatin in
      diabetic nephropathy.
AB  - INTRODUCTION: We aimed to evaluate the high-sensitivity C-reactive protein (HS
      CRP) level changes at the beginning and after withdrawal of lovastatin therapy in
      patients with diabetic nephropathy. MATERIALS AND METHODS: Thirty male patients
      with type 2 diabetes mellitus and diabetic nephropathy were enrolled in the
      study. Lovastatin, 20 mg/d, was administered for 90 days. Afterwards, Lovastatin
      was withdrawn for the next 30 days. Blood samples were obtained before the
      intervention, on the 90th day, and days 1, 7, and 30 after withdrawal of
      Lovastatin. Serum level of HS-CRP was determined by enzyme-linked immunosorbent
      assay. Alterations in lipid profile was assessed, as well, and compared with that
      of HS-CRP. RESULTS: Serum level of HS-CRP was significantly reduced after 90 days
      of lovastatin therapy (P < .001). Then, the HS-CRP reached the pretreatment
      baseline level on the 7th day after lovastatin withdrawal and maintained until
      the 30th day (P < .001). Serum HS-CRP changes showed no significant association
      with lipid profile except for serum total cholesterol level (r = 0.9, P = .006)
      after 3 months of lovastatin therapy. Their association was re-evaluated after 7
      days and 1 month of treatment withdrawal and no significant correlations were
      found. CONCLUSIONS: Our findings suggest that lovastatin decreases serum CRP
      level in patients with diabetic nephropathy, and 7 days after lovastatin
      cessation, CRP level increases again.

PMID- 19395786
TI  - NPHS2 mutations in children with steroid-resistant nephrotic syndrome.
AB  - INTRODUCTION: Congenital nephrotic syndrome may be caused by mutations in NPHS1
      and NPHS2, which encode nephrin and podocin, respectively. Since the
      identification of the NPHS2 gene, various investigators have demonstrated that
      its mutation is an important cause of steroid-resistant nephrotic syndrome. We
      aimed to evaluate frequency and spectrum of podocin mutations in the Iranian
      children with steroid-resistant nephritic syndrome. MATERIALS AND METHODS: We
      examined 20 children with steroid-resistant nephritic syndrome referred to Ali
      Asghar Children's Hospital, in Tehran, Iran. Mutations in the 5th and 7th exons
      of NPHS2 were assessed. The mutational analysis of NPHS2 was performed by DNA
      sequencing. RESULTS: The mean age at the onset of proteinuria was 6.4 +/- 3.6
      years. None of the children had mutations in the exons 5 or 7. CONCLUSIONS: Our
      study suggests that NPHS2 mutations in exons 5 and 7 are not seen in our
      children. Therefore, we cannot recommend NPHS2 (exons 5 and 7) mutation for
      screening in Iranian children with steroid-resistant nephritic syndrome. Other
      exons of podocin or other podocyte proteins in Iranian children may play a role
      in pathogenesis of steroid-resistant nephritic syndrome.

PMID- 19395787
TI  - Costs and length of hospitalizations following kidney transplantation.
AB  - INTRODUCTION: We assessed the costs of hospital admissions and length of hospital
      stay in kidney allograft recipients admitted to our center, in order to rank
      hospitalization causes in terms of costly and prolonged admissions, to bring to
      light the respective correlates of costly and prolonged admissions, and to
      investigate the relationship between costs and length of rehospitalizations.
      MATERIALS AND METHODS: In a retrospective study at Baqyiatallah Hospital, in
      Tehran, records of 358 posttransplant hospitalizations were reviewed for the
      costs and duration of hospital stay. The causes of rehospitalizations, relative
      frequency of prolonged stays in costly rehospitalizations, and also relative
      frequency of costly admissions in short and prolonged stays were evaluated.
      RESULTS: Among rehospitalizations, 83.3% of those due to cerebrovascular accident
      were costly and 51% of those with graft rejection resulted in prolonged hospital
      stays. Costly admissions had a high regularity in cases of patients older than 60
      years, end-stage renal disease due to diabetes mellitus, graft loss, intensive
      care unit admission, and hospitalizations accompanied by in death. Prolonged
      stays were more common in those who were admitted to intensive care unit and
      those who ultimately died. The Costs showed a significant correlation with the
      length of rehospitalization (r = 0.626, P = .001). CONCLUSIONS: The strong
      correlation between the length of hospitalization and posttransplant
      hospitalization costs means that the former should be curtailed by focusing on
      such correlates of high-cost admissions as high age and diabetes mellitus as the
      cause of kidney failure.

PMID- 19395788
TI  - Brucellosis with kidney failure.
AB  - Brucellosis is a multisystem disease that may present with a broad spectrum of
      clinical manifestations. The most frequent symptoms are constitutional symptoms.
      While involvement of the bones, joints, and liver is not rare, brucellosis may
      rarely involve the kidney. We present a case of brucellosis with hepatitis,
      pancytopenia, peripheral arthritis, and kidney failure.

PMID- 19395789
TI  - Nephroquiz 1: cyclophosphamide or mycofenolate mofetil?

PMID- 19395790
TI  - Frequency of candiduria in inpatients and outpatients in department of Urology,
      Golestan Hospital, Ahvaz, Iran.

PMID- 19395792
TI  - World Kidney Day 2009 Activities in Iran.

PMID- 19395793
TI  - Analyses of the factors for the demagnetization of permanent magnets caused by
      high-energy electron irradiation.
AB  - Demagnetization owing to high-energy electron irradiation has been analyzed for
      permanent magnets used in insertion devices of synchrotron radiation sources,
      using the Monte Carlo code FLUKA. The experimental data of a thermally treated
      Nd(2)Fe(14)B permanent magnet with a copper or a tantalum block at electron
      energies ranging from 2 to 8 GeV were compared with the calculation data of the
      absorbed doses, photoneutron production distributions and star densities. The
      results indicate that low-energy photoneutrons and bremsstrahlung photons are not
      involved in the demagnetization process, and suggest that the star density owing
      to the photoneutrons is strongly correlated with the demagnetization process.

PMID- 19395794
TI  - Characterization of germanium linear kinoform lenses at Diamond Light Source.
AB  - The unprecedented brilliance achieved by third-generation synchrotron sources and
      the availability of improved optics have opened up new opportunities for the
      study of materials at the micrometre and nanometre scale. Focusing the
      synchrotron radiation to smaller and smaller beams is having a huge impact on a
      wide research area at synchrotrons. The key to the exploitation of the improved
      sources is the development of novel optics that deliver narrow beams without loss
      of brilliance and coherence. Several types of synchrotron focusing optics are
      successfully fabricated using advanced miniaturization techniques. Kinoform
      refractive lenses are being developed for hard X-ray beamlines, and the first
      test results at Diamond are discussed in this paper.

PMID- 19395795
TI  - MicroGISAXS of Langmuir-Blodgett protein films: effect of temperature on long
      range order.
AB  - The grazing-incidence small-angle X-ray scattering technique has been used here
      with a microfocus beamline (microGISAXS) to study the effect of temperature on
      the protein reorganization taking place in a Langmuir-Schaefer multilayered
      enzyme film. The study appears quite reproducible in the two enzymes being
      utilized, penicillin G acylase and urease. In-plane and out-of-plane cuts are
      used to account for the changes in the film thickness and distance between
      structures taking place by the process of heating up to 423 K and cooling to room
      temperature. The out-of-plane cut suggests that the structures are getting closer
      and are becoming more organized owing to the heating affect. Merging of layers is
      likely to occur during the heating and cooling process, leading to a loss of
      correlation between the interfaces of the layers and to the establishment of long
      range order. The dramatic increase in long-range order in the Langmuir-Blodgett
      multilayered enzyme films after heating and cooling, made here apparent by
      grazing-incidence small-angle X-ray scattering using a microbeam, could in the
      future open the way to avoiding the bottleneck of protein crystallization for
      protein structure determination.

PMID- 19395796
TI  - Quality evaluation of quick-frozen biological specimens by simultaneous microbeam
      SAXS/WAXS recordings.
AB  - The quality of small-angle X-ray scattering (SAXS) patterns from quick-frozen
      hydrated biological specimens was correlated with the extent of ice crystal
      formation by simultaneously recording wide-angle X-ray scattering (WAXS) of ice,
      at a micrometer-order spatial resolution by using X-ray microbeams. Flight muscle
      fibers from a giant waterbug, Lethocerus, known to generate well defined small
      angle reflection spots originating from the hexagonal lattices of myofilaments,
      were quick-frozen in the presence or absence of various cryoprotectants. Freezing
      without a cryoprotectant resulted in massive ice-crystal formation at almost all
      depths of the specimen, and the occurrence of reflection spots was limited to the
      region close to the specimen surface. Inclusion of 20% dimethyl sulfoxide or
      methylpentanediol ensured ideal vitreous ice formation and good diffraction
      qualities for up to 100 microm from the specimen surface. Glycerol and sucrose
      were found to be inferior at a 20% concentration, but left the reflection spots
      observable at depths of up to 100 microm. Thus, the microbeam SAXS/WAXS recording
      offers a high-spatial-resolution means of evaluating the extent of structure
      preservation of quick-frozen biological specimens. The technique presented here
      may also provide useful information in cryoelectron microscopy.

PMID- 19395797
TI  - A new ultra-high-vacuum variable temperature and high-magnetic-field X-ray
      magnetic circular dichroism facility at LNLS.
AB  - X-ray magnetic circular dichroism (XMCD) is one of the most powerful tools for
      investigating the magnetic properties of different types of materials that
      display ferromagnetic behavior. Compared with other magnetic-sensitive
      techniques, XMCD has the advantage of being element specific and is capable of
      separating the spin and magnetic moment contributions associated with each
      element in the sample. In samples involving, for example, buried atoms, clusters
      on surfaces or at interfaces, ultrathin films, nanoparticles and nanostructures,
      three experimental conditions must be present to perform state-of-the-art XMCD
      measurements: high magnetic fields, low temperatures and an ultra-high-vacuum
      environment. This paper describes a new apparatus that can be easily installed at
      different X-ray and UV beamlines at the Brazilian Synchrotron Light Laboratory
      (LNLS). The apparatus combines the three characteristics described above and
      different methods to measure the absorption signal. It also permits in situ
      sample preparation and transfer to another chamber for measurement by
      conventional surface science techniques such as low-energy electron diffraction
      (LEED), reflection high-energy electron diffraction (RHEED), X-ray photoelectron
      spectroscopy (XPS) and X-ray photoelectron diffraction (XPD). Examples are given
      of XMCD measurements performed with this set-up on different materials.

PMID- 19395798
TI  - X-ray diffractometry for the structure determination of a submicrometre single
      powder grain.
AB  - A high-precision diffractometer has been developed for the structure analysis of
      a submicrometre-scale single grain of a powder sample at the SPring-8 BL40XU
      undulator beamline. The key design concept is the combination of a stable focused
      synchrotron radiation beam and the precise axis control of the diffractometer,
      which allows accurate diffraction intensity data of a submicrometre-scale single
      powder grain to be measured. The phase zone plate was designed to create a high
      flux focused synchrotron radiation beam. A low-eccentric goniometer and high
      precision sample positioning stages were adopted to ensure the alignment of a
      micrometre-scale focused synchrotron radiation beam onto the submicrometre-scale
      single powder grain. In order to verify the diffractometer performance, the
      diffraction pattern data of several powder grains of BaTiO(3), of dimensions
      approximately 600 x 600 x 300 nm, were measured. By identifying the diffraction
      data set of one single powder grain, the crystal structure was successfully
      determined with a reliable factor of 5.24%.

PMID- 19395799
TI  - Development of new apertures for coherent X-ray experiments.
AB  - When one performs a coherent small-angle X-ray scattering experiment, the
      incident beam must be spatially filtered by slits on a length scale smaller than
      the transverse coherence length of the source which is typically around 10
      microm. The Fraunhofer diffraction pattern of the slit is one of the important
      sources of background in these experiments. New slits which minimize this
      parasitic background have been designed and tested. The slit configuration
      apodizes the beam by the use of partially transmitting inclined slit jaws. A
      model is presented which predicts that the high wavevector tails of the
      diffraction pattern fall as the inverse fourth power of the wavevector instead of
      the inverse second power that is observed for standard slits. Using cleaved GaAs
      single-crystal edges, Fraunhofer diffraction patterns from 3 and 5.5 keV X-rays
      were measured, in agreement with the theoretical model proposed. A novel phase
      peak diffraction pattern associated with phase variations of the transmitted
      electric field was also observed. The model proposed adequately accounts for this
      phenomenon.

PMID- 19395800
TI  - Performance of single-photon-counting PILATUS detector modules.
AB  - PILATUS is a silicon hybrid pixel detector system, operating in single-photon
      counting mode, that has been developed at the Paul Scherrer Institut for the
      needs of macromolecular crystallography at the Swiss Light Source (SLS). A
      calibrated PILATUS module has been characterized with monochromatic synchrotron
      radiation. The influence of charge sharing on the count rate and the overall
      energy resolution of the detector were investigated. The dead-time of the system
      was determined using the attenuated direct synchrotron beam. A single module
      detector was also tested in surface diffraction experiments at the SLS, whereby
      its performance regarding fluorescence suppression and saturation tolerance were
      evaluated, and have shown to greatly improve the sensitivity, reliability and
      speed of surface diffraction data acquisition.

PMID- 19395801
TI  - Development of micro-XANES mapping in the diamond anvil cell.
AB  - Energy-dispersive X-ray absorption spectroscopy is now a well established method
      that has been applied to a broad range of applications. At the energy-dispersive
      EXAFS beamline of the ESRF, ID24, the recently achieved 5 x 5 microm focal spot
      combined with fast acquisition has allowed complex and non-uniform samples to be
      mapped and images to be obtained where each pixel contains full XAS information.
      This method has been applied to a study under extreme conditions of pressure and
      temperature in a diamond anvil cell in transmission mode. The case study was the
      investigation of the Fe K-edge XANES of (Mg,Fe)SiO(3)-perovskite and (Mg,Fe)O
      ferropericlase on decomposition of the spinel-structured olivine [gamma
      (Mg,Fe)(2)SiO(4)] at 78 (3) GPa after laser heating at 2200 (100) K.

PMID- 19395802
TI  - Universal function for the brilliance of undulator radiation considering the
      energy spread effect.
AB  - Angular and spatial profiles of undulator radiation have been investigated to
      derive a universal function that evaluates the brilliance of undulator radiation
      and takes into account the effects of electron beam emittance and energy spread.
      It has been found that the effects of energy spread on the angular divergence and
      source size can be expressed by simple analytic expressions, and a universal
      brilliance function has been derived by convolution with the electron beam
      distribution functions. Comparisons with numerical results have been carried out
      to show the validity and applicability of the universal function.

PMID- 19395803
TI  - Picosecond time-resolved laser pump/X-ray probe experiments using a gated single
      photon-counting area detector.
AB  - The recent developments in X-ray detectors have opened new possibilities in the
      area of time-resolved pump/probe X-ray experiments; this article presents the
      novel use of a PILATUS detector to achieve X-ray pulse duration limited time
      resolution at the Advanced Photon Source (APS), USA. The capability of the gated
      PILATUS detector to selectively detect the signal from a given X-ray pulse in 24
      bunch mode at the APS storage ring is demonstrated. A test experiment performed
      on polycrystalline organic thin films of alpha-perylene illustrates the
      possibility of reaching an X-ray pulse duration limited time-resolution of 60 ps
      using the gated PILATUS detector. This is the first demonstration of X-ray pulse
      duration limited data recorded using an area detector without the use of a
      mechanical chopper array at the beamline.

PMID- 19395804
TI  - 100 ps time-resolved solution scattering utilizing a wide-bandwidth X-ray beam
      from multilayer optics.
AB  - 100 ps time-resolved X-ray solution-scattering capabilities have been developed
      using multilayer optics at the beamline NW14A, Photon Factory Advanced Ring, KEK.
      X-ray pulses with an energy bandwidth of DeltaE/E = 1-5% are generated by
      reflecting X-ray pulses (DeltaE/E = 15%) through multilayer optics, made of
      W/B(4)C or depth-graded Ru/C on silicon substrate. This tailor-made wide
      bandwidth X-ray pulse provides high-quality solution-scattering data for
      obtaining photo-induced molecular reaction dynamics. The time-resolved solution
      scattering of CH(2)I(2) in methanol is demonstrated as a typical example.

PMID- 19395805
TI  - Simple dose rate measurements for a very high synchrotron X-ray flux.
AB  - Dose measurements based on methylene blue (MB) bleaching, widely used for
      ultraviolet light, can also be applied to X-rays including very high flux levels.
      This method has been tested by using both MB bleaching and Fricke dosimetry for a
      conventional monochromatic X-ray source and then for 'white-beam' synchrotron
      radiation. The results show that MB bleaching dosimetry can easily measure X-ray
      doses up to at least 10(5) Gy s(-1), as long as the MB concentration is
      sufficiently high. This condition can be verified from the deviations from
      linearity of the bleaching versus exposure time.

PMID- 19395806
TI  - Evaluation of enamel crystallites in subsurface lesion by microbeam X-ray
      diffraction.
AB  - Early caries lesion is a demineralization process that takes place in the top 0.1
      mm layer of tooth enamel. In this study, X-ray microbeam diffraction was used to
      evaluate the hydroxyapatite crystallites in the subsurface lesion of a bovine
      enamel section and the results are compared with those obtained by transversal
      microradiography, a method commonly used for evaluation of tooth mineral.
      Synchrotron radiation from SPring-8 was used to obtain a microbeam with a
      diameter of 6 microm. Wide-angle X-ray diffraction reports the amount of
      hydroxyapatite crystals, and small-angle X-ray scattering reports that of voids
      in crystallites. All three methods showed a marked decrease in the enamel density
      in the subsurface region after demineralization. As these diffraction methods
      provide structural information in the nanometre range, they are useful for
      investigating the mechanism of the mineral loss in early caries lesion at a
      nanometre level.

PMID- 19395807
TI  - Origin of the X-ray magnetic circular dichroism at the L-edges of the rare-earths
      in RxR(1-x)'Al2 systems.
AB  - An X-ray magnetic circular dichroism (XMCD) study performed at the rare-earth
      L(2,3)-edges in the R(x)R(1-x)'Al(2) compounds is presented. It is shown that
      both R and R' atoms contribute to the XMCD recorded at the L-edges of the
      selected rare-earth, either R or R'. The amplitude of the XMCD signal is not
      directly correlated to the magnetization or to the value of the individual (R,
      R') magnetic moments, but it is related to the molecular field acting on the rare
      earth tuned in the photoabsorption process. This result closes a longstanding
      study of the origin of the XMCD at the L-edge of the rare-earths in multi
      component systems, allowing a full understanding of the exact nature of these
      signals.

PMID- 19395808
TI  - Biological X-ray absorption spectroscopy and metalloproteomics.
AB  - In the past seven years the size of the known protein sequence universe has been
      rapidly expanding. At present, more then five million entries are included in the
      UniProtKB/TrEMBL protein database. In this context, a retrospective evaluation of
      recent X-ray absorption studies is undertaken to assess its potential role in
      metalloproteomics. Metalloproteomics is the structural and functional
      characterization of metal-binding proteins. This is a new area of active research
      which has particular relevance to biology and for which X-ray absorption
      spectroscopy is ideally suited. In the last three years, biological X-ray
      absorption spectroscopy (BioXAS) has been included among the techniques used in
      post-genomics initiatives for metalloprotein characterization. The emphasis of
      this review is on the progress in BioXAS that has emerged from recent meetings in
      2007-2008. Developments required to enable BioXAS studies to better contribute to
      metalloproteomics throughput are also discussed. Overall, this paper suggests
      that X-ray absorption spectroscopy could have a higher impact on
      metalloproteomics, contributing significantly to the understanding of metal site
      structures and of reaction mechanisms for metalloproteins.

PMID- 19395809
TI  - Characterizing arsenic in preserved hair for assessing exposure potential and
      discriminating poisoning.
AB  - Advanced analytical techniques have been used to characterize arsenic in
      taxidermy specimens. Arsenic was examined to aid in discriminating its use as a
      preservative from that incorporated by ingestion and hence indicate poisoning (in
      the case of historical figures). The results are relevant to museum curators,
      occupational and environmental exposure concerns, toxicological and
      anthropological investigations. Hair samples were obtained from six taxidermy
      specimens preserved with arsenic in the late 1800s and early 1900s to investigate
      the arsenic incorporation. The presence of arsenic poses a potential hazard in
      museum and private collections. For one sample, arsenic was confirmed to be
      present on the hair with time-of-flight secondary ion mass spectrometry and then
      measured with neutron activation analysis to comprise 176 microg g(-1). The hair
      cross section was analysed with synchrotron micro-X-ray fluorescence to
      investigate the transverse distribution of topically applied arsenic. It was
      found that the arsenic had significantly penetrated all hair samples. Association
      with melanin clusters and the medulla was observed. Lead and mercury were also
      identified in one sample. X-ray absorption near-edge spectroscopy of the As K
      edge indicated that an arsenate species predominantly existed in all samples;
      however, analysis was hindered by very rapid photoreduction of the arsenic. It
      would be difficult to discriminate arsenic consumption from topically applied
      arsenic based on the physical transverse distribution. Longitudinal distributions
      and chemical speciation may still allow differentiation.

PMID- 19395810
TI  - An XANES study on the modification of single-walled carbon nanotubes by nitric
      acid.
AB  - X-ray absorption near-edge structure (XANES) spectroscopy has been applied to
      identify the modification process of single-walled carbon nanotubes (SWCNTs)
      treated by nitric acid. The carboxyl groups created by the nitric acid treatment
      have been found to be formed on both the carbonaceous fragments and the side
      walls of SWCNTs. The carbonaceous fragments could be removed by a following
      washing treatment with sodium hydroxide. XANES spectra indicate that carbonaceous
      fragments are the result of the synthesis process and/or of the nitric acid
      treatment. Tube walls of SWCNTs are weakly oxidized by the nitric acid treatment
      although, after removing carbonaceous fragments, a direct oxidation process of
      SWCNTs is observed. Experimental data address the removal of carbonaceous
      fragments on SWCNTs as an efficient method for side-wall modification of a SWCNT.

PMID- 19395811
TI  - Synchrotron-based radioscopy employing spatio-temporal micro-resolution for
      studying fast phenomena in liquid metal foams.
AB  - Investigations of pore coalescence and individual cell wall collapse in an
      expanding liquid metal foam by means of X-ray radioscopy with spatio-temporal
      micro-resolution are reported. By using white synchrotron radiation for imaging,
      the rupture of a film and the subsequent merger of two neighbouring bubbles could
      be recorded with a time sampling rate of 40000 frames s(-1) (25 micros exposure
      time) and a spatial sampling rate of 20 microm. The rupture time of a cell wall
      was found to be in the range of 300 micros. This value is in agreement with
      theoretical considerations which assume an inertia-dominated rupture time of cell
      walls in liquid metal foams.

PMID- 19395812
TI  - Comments on Migration of mercury from dental amalgam through human teeth by H. H.
      Harris et al. (2008). J. Synchrotron Rad. 15, 123-128.

PMID- 19395816
TI  - Evidence-based medicine again.

PMID- 19395817
TI  - The nature of evidence in evidence-based medicine: guest editors' introduction.

PMID- 19395818
TI  - Iconoclast or creed? Objectivism, pragmatism, and the hierarchy of evidence.
AB  - Because "evidence" is at issue in evidence-based medicine (EBM), the critical
      responses to the movement have taken up themes from post-positivist philosophy of
      science to demonstrate the untenability of the objectivist account of evidence.
      While these post-positivist critiques seem largely correct, I propose that when
      they focus their analyses on what counts as evidence, the critics miss important
      and desirable pragmatic features of the evidence-based approach. This article
      redirects critical attention toward EBM's rigid hierarchy of evidence as the
      culprit of its objectionable epistemic practices. It reframes the EBM discourse
      in light of a distinction between objectivist and pragmatic epistemology, which
      allows for a more nuanced analysis of EBM than previously offered: one that is
      not either/or in its evaluation of the decision-making technology as either
      iconoclastic or creedal.

PMID- 19395819
TI  - Justice in health research: What is the role of evidence-based medicine?
AB  - Evidence-based medicine (EBM) aims to facilitate access to up-to-date, accurate
      information about the effectiveness of medical interventions, in order to improve
      human health. The quality of the research results available for EBM processes of
      synthesis and meta-analysis is critical to this process. If there are distortions
      or corruptions in the research process, EBM becomes a false prophet, collecting
      and propagating unreliable results. This article examines flaws in the current
      processes of research production and the implications of these for justice and
      for vulnerable patients, and explores possible solutions.

PMID- 19395820
TI  - Sequestered evidence and the distortion of clinical practice guidelines.
AB  - As a result of the growth of evidence-based practices across the world, health
      care providers and policymakers in the United States, United Kingdom, and Europe
      have established institutes such as the United Kingdom's National Institute for
      Health and Clinical Excellence (NICE) to produce clinical guidelines that
      physicians are asked to use in their daily practice. This article discusses how
      the withholding of clinical trial information by pharmaceutical companies and
      academic researchers affects the reliability of clinical guidelines. It first
      offers a case study analysis of the U.K. drug regulator's failure to prosecute
      GlaxoSmithKline, manufacturer of the bestselling antidepressant Seroxat
      (manufactured as Paxil in North America), for withholding information on the
      safety of Seroxat from regulators. It next examines the idea of a "Sarbanes-
      Oxley for Science," a recent proposal that seeks to introduce legislation forcing
      companies to disclose clinical trials that have indeterminate or negative
      results. Legislation such as Sarbanes-Oxley for Science would solve some problems
      with the withholding of data, but not all. Until practitioners and policymakers
      address the political and legal barriers preventing full access to clinical trial
      data for all medical treatments, the ideals of evidence-based practice will
      remain elusive.

PMID- 19395821
TI  - Valuing evidence: bias and the evidence hierarchy of evidence-based medicine.
AB  - Proponents of evidence-based medicine (EBM) suggest that a hierarchy of evidence
      is needed to guide medical research and practice. Given a variety of possible
      evidence hierarchies, however, the particular version offered by EBM needs to be
      justified. This article argues that two familiar justifications offered for the
      EBM hierarchy of evidence-that the hierarchy provides special access to causes,
      and that evidence derived from research methods ranked higher on the hierarchy is
      less biased than evidence ranked lower-both fail, and that this indicates that we
      are not epistemically justified in using the EBM hierarchy of evidence as a guide
      to medical research and practice. Following this critique, the article considers
      the extent to which biases influence medical research and whether meta-analyses
      might rescue research from the influence of bias. The article concludes with a
      discussion of the nature and role of biases in medical research and suggests that
      medical researchers should pay closer attention to social mechanisms for managing
      pervasive biases.

PMID- 19395822
TI  - Theory-based medicine and the role of evidence: why the emperor needs new
      clothes, again.
AB  - The evidence-based medicine (EBM) movement was established to combat capricious
      reasoning in clinical care, particularly arguments from authority. Critique of
      authority and appraisal of evidence remain EBM's core values and should be
      revisited in this era of EBM's maturity and influence. We are now faced with a
      new form of under-questioned authority: evidence from well-designed and
      methodologically appraised randomized controlled trials (RCTs). RCT evidence is
      now prized even when it is incapable of providing meaningful information-in
      particular, when underlying causal theory is inscrutable. Experimental trial
      evidence of the effectiveness of remote intercessory prayer provides an
      illustrative case that highlights systematic scientific blind spots in the
      institutions of EBM. Medicine-even evidence-based medicine-is theory-based at its
      core. EBM must cultivate greater capacity to address the crucial role of theory
      in both the generation and use of experimental evidence.

PMID- 19395823
TI  - Some observations on observational research.
AB  - Evidence-based medicine (EBM) ranks different medical research methods on a
      hierarchy, at the top of which are randomized controlled trials (RCTs) and
      systematic reviews or meta-analyses of RCTs. Any study that does not randomly
      assign patients to a treatment or a control group is automatically placed at a
      lower level on the hierarchy. This article argues that what matters is whether
      the treatment and control groups are similar with respect to potential
      confounding factors, not whether they got that way through randomization.
      Moreover, nonrandomized studies tend to have other characteristics that make them
      useful sources of evidence, in that they tend to last longer and to enroll more
      patients than do randomized trials. Replacing the sharp dichotomy between
      randomized and nonrandomized studies with a continuum from "clean" studies (which
      have high internal validity but whose results do not readily generalize to
      clinical practice) to pragmatic studies (which are designed to more closely
      reflect clinical practice) would also make a place for outcomes research and
      research using clinical databases, which are not included in the current
      hierarchy of evidence but which can provide important information about the
      safety and efficacy of treatments.

PMID- 19395824
TI  - Making the grade: assuring trustworthiness in evidence.
AB  - Despite evidence-based medicine's (EBM's) significant evolution and maturation
      from its revolutionary origins to its current form as the preeminent means of
      practicing medicine, there are still good reasons to be unsatisfied with EBM.
      This essay explores two important new developments in EBM: recently articulated
      accounts of the scientific basis of EBM, and the related writings of the GRADE
      Working Group to create standards for interpretation of the medical literature
      and evaluation of recommendations. A review of Karanicolas, Kunz, and Guyatt's
      (2008) three-step articulation of EBM's scientific basis demonstrates that the
      supposed soundness of each principle is not attributable to its scientific
      status; instead, the normative language of each principle highlights EBM's
      grounding in an only partially articulated philosophical framework. The GRADE
      Working Group's effort similarly relies on credibility, consensus, and trust in
      its defense and justification of EBM. These recent developments in EBM reveal
      that if the clinical research literature is to be informative or foundational to
      the enterprise of health care, much work needs to be done to secure its
      trustworthiness and integrity. An agenda for examining trust and trustworthiness
      in the context of health research is proposed.

PMID- 19395825
TI  - Ethics and evidence in psychiatric practice.
AB  - Many psychiatrists have endorsed the idea of evidence-based psychiatry, the
      application of the principles of evidence-based medicine (EBM) to psychiatric
      practice. Proponents of an evidence-based approach to psychiatry hope that if
      practice is driven by "hard" scientific data, there will be greater potential to
      help patients. In other words, advocates of evidence-based psychiatry aim to
      bolster psychiatry's ethical standing through scientific evidence. Can EBM
      provide this ethical substantiation to psychiatry? This article provides an
      overview of some of the main ethical issues within psychiatry and examines three
      interrelated questions: (1) to which ethical values is EBM committed? (2) which
      ethical theory is reflected in these values? and (3) can these values and
      theories resolve existing ethical issues in psychiatry? EBM strives for the
      "greatest good for the greatest number," where good is defined as improved
      health. This utilitarian orientation cannot, however, address critical areas of
      moral importance for psychiatry, such as how its practitioners differentiate
      normal from abnormal, how they determine which forms of suffering should be
      alleviated through psychiatric means, and when involuntary intervention is
      ethically justified. The ethical principles implicit in EBM are too limited to
      serve as an ethical basis for psychiatry.

PMID- 19395826
TI  - Complementary and alternative medicine: between evidence and absurdity.
AB  - Complementary/alternative medicine (CAM) has become important, particularly
      because it is widely used. This article outlines CAM's position between evidence
      and absurdity. It discusses misconceptions that often mislead the public and
      shows how CAM can and should be submitted to the principles of evidence- based
      medicine (EBM). Employing the example of acupuncture, the evidence as it
      currently stands is described. But there are numerous obstacles to applying EBM
      to CAM. EBM is defenseless against absurdity. We should, therefore, demarcate the
      absurd in order to avoid wasting time and resources. The new fad of "integrated"
      medicine has been proposed as a potential replacement for EBM.

PMID- 19395827
TI  - Evidence-based policymaking: a critique.
AB  - The idea that policy should be based on best research evidence might appear to be
      self-evident. But a closer analysis reveals a number of problems and paradoxes
      inherent in the concept of "evidence-based policymaking." The current conflict
      over evidence-based policymaking parallels a long-standing "paradigm war" in
      social research between positivist, interpretivist, and critical approaches. This
      article draws from this debate in order to inform the discussions over the
      appropriateness of evidence- based policymaking and the related question of what
      is the nature of policymaking. The positivist, empiricist worldview that
      underpins the theory and practice of evidence-based medicine (EBM) fails to
      address key elements of the policymaking process. In particular, a narrowly
      "evidence-based" framing of policymaking is inherently unable to explore the
      complex, context-dependent, and value-laden way in which competing options are
      negotiated by individuals and interest groups. Sociolinguistic tools such as
      argumentation theory offer opportunities for developing richer theories about how
      policymaking happens. Such tools also have potential practical application in the
      policymaking process: by enhancing participants' awareness of their own values
      and those of others, the quality of the collective deliberation that lies at the
      heart of policymaking may itself improve.

PMID- 19395828
TI  - Evidence-free medicine: forgoing evidence in clinical decision making.
AB  - Despite being the central concept to evidence-based medicine (EBM), evidence
      remains an elusive and controversial notion. Ongoing debates regarding evidence
      primarily serve to confuse and obfuscate. Examination of the nature of medical
      decision making without any appeal to evidence reveals a more complete
      understanding of the optimal practice of clinical medicine. An "evidence-free
      medicine" allows for the incorporation of a variety of facts and warrants,
      reasons and reasoning, into clinical decisions. The relative weighting of
      potentially conflicting warrants for a medical decision comprises the critical
      process of clinical judgment. Forgoing evidence allows clinical medicine to once
      again be a personal and prudential undertaking, arising from and focused on the
      individual patient.

PMID- 19395829
TI  - A footnote to the revolution in psychiatric diagnosis.

PMID- 19395830
TI  - A note from the editor.

PMID- 19395831
TI  - Health information technology: addressing health disparity by improving quality,
      increasing access, and developing workforce.

PMID- 19395832
TI  - Supports and obstacles in the medical school application process for American
      Indians and Alaska Natives.
AB  - PURPOSE: This study examines how a wide range of supports and obstacles are
      associated with the medical school admissions process of American Indians and
      Alaska Natives (AI/ANs), an under-studied population. METHOD: All AI/AN
      applicants to the University of Washington School of Medicine during the 2002
      2004 admissions cycles were sent a mail-in survey with numerical and open-ended
      items. We analyzed admissions data for all 107 applicants and data on supports
      and obstacles for 34 survey respondents. RESULTS: Compared with respondents
      accepted by at least one medical school, rejected respondents were older, more
      often were parents, submitted fewer applications, and reported receiving less
      support for the medical school application process. Obstacles included difficulty
      with the Medical College Admission Test, insufficient finances, and poor
      information about the process. CONCLUSION: A conceptual framework that considers
      both supports and obstacles in the medical school application process will
      improve our understanding of the needs of AI/AN applicants.

PMID- 19395833
TI  - Developing a disaster preparedness campaign targeting low-income Latino
      immigrants: focus group results for project PREP.
AB  - Low-income immigrant Latinos are particularly vulnerable to disasters because
      they are both ill-prepared and disproportionately affected. Disaster preparedness
      programs that are culturally appropriate must be developed and tested. To develop
      such a program, we conducted 12 focus groups with low-income immigrant Latinos to
      understand their perceptions and understanding of disaster preparedness, and
      facilitators and obstacles to it. Participants were concerned about remaining
      calm during an earthquake. Obstacles to storage of disaster supplies in a kit and
      developing a family communication plan were mentioned frequently.
      Misunderstandings were voiced about the proper quantity of water to store and
      about communication plans. Several focus groups spontaneously suggested small
      group discussions (platicas) as a way to learn about disaster preparedness. They
      wanted specific help with building their family communication plans. They rated
      promotoras de salud highly as potential teachers. Results will guide the
      development of a disaster preparedness program tailored to the needs of low
      income Latino immigrants.

PMID- 19395834
TI  - U.S. Latino population composition change and comprehensive cancer centers.
AB  - BACKGROUND: We describe a typology characterizing population trends of U.S.
      Latinos/Hispanics from 1990 to 2000 with respect to National Cancer Institute
      designated comprehensive cancer centers (CCCs) and corresponding consolidated
      metropolitan statistical or metropolitan statistical areas (CMSA/MSAs). METHODS:
      Using U.S. Census Bureau data, we constructed population pyramids to analyze
      population growth and composition for each CMSA/MSA with a CCC. RESULTS: We
      identified four types of population growth and composition: Type I--Very Fast and
      Unstable; Type II--Fast and Unstable; Type III--Somewhat Fast and Stable; Type IV
      -Slow and Stable. CONCLUSIONS: The CCCs in areas with Types I and II population
      growth face the greatest challenges because of the lack of infrastructure for
      reaching medically underserved Latinos. In contrast, CCCs in areas with Types III
      and IV population growth may have significant infrastructure but must quickly
      develop interventions to reach and provide access to aging Latinos to reduce
      health disparities in cancer mortality and morbidity.

PMID- 19395835
TI  - Beyond medical insurance: delayed or forgone care among children in Chinese
      immigrant families.
AB  - While Asian Americans are less likely than most Americans to use health services,
      little is known about their barriers to pediatric care. This study seeks to
      describe the prevalence of delayed/forgone pediatric care and its association
      with parental acculturation status in recent-immigrant Chinese families. Survey
      data were obtained from 76 families across two community services sites. Half of
      the surveyed families reported delayed/forgone pediatric care in the previous 12
      months. Low-income families in suburban areas reported greater financial burdens,
      linguistic barriers, and a higher prevalence of delayed/forgone care than low
      income families living in downtown area. Middle class immigrant families reported
      cultural barriers as a reason for delayed/forgone care. Traditional beliefs and
      not medical insurance were significant predictors of delayed/forgone care.
      Culturally and linguistically appropriate studies on risk reduction interventions
      will be needed to address the linguistic and cultural barriers to health care
      access.

PMID- 19395836
TI  - Health needs in Brooklyn's Chinatown: a pilot assessment using rapid
      participatory appraisal.
AB  - BACKGROUND: The relatively new Chinatown of Brooklyn is medically underserved. A
      pilot assessment of the health needs of this community was conducted using Rapid
      Participatory Appraisal. METHODS: In-depth interviews with health professionals
      and community members plus searches of national, state, and local electronic
      health databases were conducted taking into account multiple determinants of
      health. RESULTS: Community organization, sociological factors, services, and
      policy were all partly responsible for unmet health needs, including the lack of
      an overall community structure related to health. Health concerns of all kinds
      were exacerbated by poverty, language barriers, immigration status, culture, and
      the need for acculturation. Significant health assets were present but were not
      adequate to address needs. DISCUSSION: While each health concern had its own
      unique identifiable causes, the interaction of these concerns and the limitations
      of assets at all levels make solutions difficult.

PMID- 19395837
TI  - Generational cohorts, age at arrival, and access to health services among Asian
      and Latino immigrant adults.
AB  - Recent immigrant assimilation literature has highlighted the tremendous
      heterogeneity that exists within foreign-born and U.S.-born second generation
      populations-and thus, the importance of a broader generational cohort framework
      that encompasses nativity, immigrant generation, age at arrival, and parental
      nativity. Using data from the 2003 California Health Interview Survey, this paper
      examines generational cohort differences in access to health services among Asian
      and Latino immigrant adults. Results showed that immigrants arriving in the U.S.
      as children had better access to services, one exception being middle-aged and
      older Asians. Individuals arriving in the U.S. as adults were significantly less
      likely than the third-and-later generation to have a usual source of care, and
      also had fewer physician visits. Across all cohorts, Latinos fared worse than
      both Asians and Whites. This study highlights the value of a generational cohort
      framework-specifically, the importance of age at arrival-in examining health
      access among immigrants.

PMID- 19395839
TI  - Are state Medicaid application enrollment forms readable?
AB  - We sought to assess readability and layout characteristics of state-issued
      Medicaid enrollment applications. We attempted to locate Internet-based Medicaid
      enrollment applications from each of the 50 states and the District of Columbia.
      Readability of each Medicaid enrollment application "Signature" page was
      calculated using McLaughlin's Simplified Measure of Gobbledygoop formula, while
      layout characteristics were assessed utilizing criteria included in the User
      Friendliness Tool. Readability of Medicaid enrollment application Signature pages
      ranged from 11th to 18th grade level (M+/-SD=15.5+/-1.5). Most (66%) applications
      did not use a recommended font size (> or =12 point). None of the applications
      required little work to make them comply with good formatting standards according
      to the User-Friendliness Tool. Medicaid enrollment applications overall exhibit
      text font sizes below 12 point, crowded formatting, and excessively high reading
      demands. State health departments should revise their Medicaid enrollment
      applications to adhere to established low-literacy guidelines to improve
      understanding and comprehension by potential enrollees.

PMID- 19395838
TI  - Providing access to specialty care for severely disabled institutional residents:
      an academic health center telemedicine model.
AB  - The UT Southwestern Virtual Wound Care Clinic provides care to disabled
      institutional residents in an urban setting. The program offers flexible
      financial mechanisms for residents of the facility to access specialty care.
      Telemedicine improves quality-of-life and reduces costs by minimizing patient
      transportation. The exchange of clinical knowledge benefits both parties.

PMID- 19395840
TI  - Diabetes disease management results in Hispanic Medicaid patients.
AB  - OBJECTIVES: To investigate outcomes of a telephonic nursing disease management
      program for Medicaid patients with diabetes residing in Puerto Rico. STUDY
      DESIGN: A 12-month, matched-cohort study. STUDY POPULATION: Four hundred and
      ninety (490) intervention group members matched to 490 controls. INTERVENTION:
      Disease management diabetes program. For those in the intervention group, the
      disease management program customized a self-management intervention plan. MAIN
      OUTCOME MEASURES: Medical service utilization, including hospitalizations,
      emergency department visits, physician evaluation and management visits, selected
      clinical indicators, and financial impact. RESULTS: The intervention group showed
      significant effects compared with the control group, including a 48% reduction in
      inpatient bed days, and a 23% increase in ACE inhibitor use, resulting in a
      return on investment estimate of 3.8:1. CONCLUSIONS: The study demonstrates that
      a nursing disease management program for diabetes can significantly improve
      hospitalizations, drug compliance, and vaccinations in a Hispanic Medicaid
      population.

PMID- 19395841
TI  - Inpatient hospital service utilization of the uninsured in Nebraska: policy
      implications for addressing uncompensated care.
AB  - In order better to inform policymakers about financing uncompensated hospital
      care through appropriate allocation of resources among Nebraska communities, this
      study used seven years (1996-2002) of county-level data from multiple sources to
      examine the relationship between population economic factors and the hospital
      inpatient care use by uninsured patients. The generalized estimating equation
      (GEE) regression analysis showed that, at the county level, the population
      uninsurance rate and other economic factors (e.g., per capita income, the
      percentage of population receiving welfare) are statistically significant
      predictors of average hospital self-pay inpatient charge per resident. Residents
      in the three western regions of the state also incurred statistically higher per
      resident hospital self-pay inpatient charges than did their counterparts in the
      three eastern regions. State policymakers in Nebraska can use our study results
      to allocate resources on the basis of community economic characteristics and
      geographic location, to help reduce the financial burden of caring for the
      uninsured to safety net hospitals. The study may have a wide application to other
      states examining the same policy issues. The model used in this study can be
      easily created for other states, as the required data are readily available.

PMID- 19395842
TI  - Preventive dental service utilization for Medicaid-enrolled children in New
      Hampshire: a comparison of care provided by pediatric dentists and general
      dentists.
AB  - In this study, we compared preventive dental utilization through visits to a
      pediatric dentist (PD) vs. visits to a general dentist (GD) among Medicaid
      enrolled children in New Hampshire (n = 12,964). Dental claims were analyzed
      using conditional logistic regression models. After adjusting for covariates,
      children seen by a PD were 51% more likely to have received fluoride treatment,
      26% more likely to have had at least two dental examinations, and 19% more likely
      to have received a sealant than children seen by a GD. Overall, our results
      suggest that children seen by a PD were more likely to have received preventive
      services than those seen by a GD. Because Medicaid-enrolled children are at
      increased risk for poor oral health, policies should be enacted to ensure that
      high-risk children receive appropriate and regular prevention-oriented dental
      care.

PMID- 19395843
TI  - Are there patient disparities when electronic health records are adopted?
AB  - Using nationally representative samples of visits from the 2005-2006 National
      Ambulatory Medical Care Surveys and the National Hospital Ambulatory Medical Care
      Surveys (N=39,343), this study examines whether electronic health record (EHR)
      systems have been adopted by primary care physicians or providers (PCPs) for poor
      minority patients at the same rate as by the PCPs for wealthier non-minority
      patients. Although we found that electronic health record adoption rates varied
      primarily by type of practice of the PCP, we also found that uninsured Black and
      Hispanic or Latino patients, as well as Hispanic or Latino Medicaid patients were
      less likely to have PCPs using EHRs, compared with privately-insured White
      patients, after controlling for PCPs' practice type and location, as well as
      patient characteristics. This finding reflects a mixture of high and low EHR
      adopters among PCPs for poor minority patients.

PMID- 19395844
TI  - Point-of-sale marketing of tobacco products: taking advantage of the socially
      disadvantaged?
AB  - With increasing regulation of tobacco industry marketing practices, point-of-sale
      advertising has become an important channel for promoting tobacco products. One
      hundred and ten convenience stores in Oklahoma County were surveyed for tobacco
      related advertising. There were significantly more point-of-sale tobacco
      advertisements in low-income and minority neighborhoods than in better educated,
      higher-income, predominantly White neighborhoods. Storeowners or managers were
      also interviewed to determine who has decision-making power regarding store
      signage and placement, and to elicit perceptions of industry tactics. Contracts
      with tobacco companies leave storeowners with little or no control over promotion
      of tobacco products within their store, and many are unaware of the implications
      of the tobacco industry point-of-sale practices. Local ordinances that regulated
      outdoor signage reduced outdoor tobacco advertisements, as well as tobacco
      signage and promotions within the store. Policy change, rather than education
      targeting storeowners, is recommended as the most effective strategy for reducing
      point-of-sale tobacco advertising.

PMID- 19395845
TI  - Why do some health centers provide more enabling services than others?
AB  - Enabling services (such as outreach, transportation, case management, and
      discharge planning) play a critical role in improving care for vulnerable
      populations. However, these services are generally not covered by third party
      payers, making them a challenge for safety net providers that are themselves
      often financially strained. The study reported here identified organizational and
      patient population characteristics associated with enabling services provided by
      community health centers funded by the Health Resources and Services
      Administration (HRSA). Lagged regressions on 2003-2004 data from HRSA's Uniform
      Data System (n=841) indicated that health centers with more managed care
      contracts and larger staffs provided both broader scopes of enabling services and
      higher volumes of these services. Grant revenue was negatively associated with
      the volume of enabling services; however, net revenue was positively associated
      with service volume. There were several positive associations between indicators
      of patient need and the scope and volume of enabling services.

PMID- 19395846
TI  - Physical and mental health status of Hurricane Katrina evacuees in Houston in
      2005 and 2006.
AB  - OBJECTIVES: Hurricane Katrina necessitated the evacuation of over 200,000
      individuals into Houston. This study compared characteristics of three samples of
      evacuees with those of the U.S. population and examined how evacuees' experiences
      have changed over time. METHODS: Sub-populations of evacuees in Houston were
      surveyed immediately following the hurricane, two months afterwards, and one year
      later. Demographic characteristics, socioeconomic status, physical and mental
      health status, and access to care of the most disadvantaged evacuees in Houston
      were analyzed. RESULTS: Predominantly, evacuees surveyed were Black, low-income,
      unemployed, and facing challenges accessing health care. Twenty-eight percent
      felt their health was worse than it was before Katrina. Almost 60% of evacuees
      reported nervousness, restlessness, worthlessness, hopelessness, and spells of
      terror or panic at least a few times a week. CONCLUSIONS: The evacuees displaced
      by the storm experienced loss of full-time employment, income, and deteriorating
      health, as well as struggles accessing necessary physical and mental health care.

PMID- 19395847
TI  - Early collaboration for adaptation: addressing depression in low-income new
      mothers.
AB  - This paper describes the development and implementation of a collaborative
      research project between a community agency and university-based researcher. The
      goal of the project was to address depression in low-income new mothers who would
      not ordinarily have access to mental health services.

PMID- 19395848
TI  - CenteringPregnancySmiles: implementation of a small group prenatal care model
      with oral health.
AB  - Preterm/low birth weights are the leading perinatal problem in the U.S., and an
      association between preterm/low birth weight outcomes and oral health has been
      identified. In response to this, a group prenatal care program-
      CenteringPregnancySmiles--was implemented in rural Kentucky in 2006. This report
      describes the model and preliminary outcomes of the CenteringPregnancySmiles
      program.

PMID- 19395849
TI  - Knowledge, attitudes, and behaviors among a sample of HIV-positive and HIV
      negative females visiting an urban VCT center in Haiti.
AB  - The knowledge, attitudes, and behaviors of over 43,000 women attending the Groupe
      Hatien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO)
      Centers in Haiti between 1999-2004 were examined. Comparative analyses were
      conducted for several sub-samples. Analyses revealed that across the entire
      sample, HIV-positive women appeared to engage in more risky behaviors than HIV
      negative women (p< .01); however, as a group, pregnant HIV-positive women
      reported safer behaviors than non-pregnant HIV-positive women (p<.01). Women from
      all groups were generally knowledgeable about the risk of HIV transmission
      through dirty needles and mother to child. However, inaccurate information about
      transmission through supernatural means and mosquitoes was very common. These
      results suggest that knowledge and education are negatively associated with HIV
      status in this sample. Addressing gaps in knowledge and behavior and reducing the
      risky behaviors of HIV-positive individuals are important directions for future
      programs.

PMID- 19395850
TI  - Relation of domestic violence to health status among Hispanic women.
AB  - Little research has addressed the association of domestic violence (DV) with
      physical and mental health in Hispanic women. We conducted a cross-sectional
      study with 146 Hispanic women patients in 2002 at an urban family medicine
      practice. Twenty-one percent of the women were identified as current victims of
      DV. Two-fifths of victims (41.9%) experienced physical and/or sexual abuse.
      Approximately two-thirds (64.5%) had depressive symptoms. Poorer mental health
      was associated with all forms of abuse. Relatively low socioeconomic status and
      acculturation level may lead to disparities in obtaining services for DV
      intervention. Culturally appropriate protocols are needed in primary care
      settings to prevent and intervene among Hispanic women at risk for DV.

PMID- 19395853
TI  - Convergent pathways link the endothelin A receptor to the beta-catenin: the beta
      arrestin connection.

PMID- 19395852
TI  - Division of labor: DNA repair and the cell cycle specific functions of the Mre11
      complex.
AB  - Genomic integrity is maintained via the concerted action of proteins that
      coordinate and control DNA replication and those that respond to DNA damage. The
      Mre11 complex is a mediator of the DNA damage response through its functions in
      DNA double strand break (DSB) sensing, checkpoint activation and recombinational
      DNA repair. The complex responds to mitotic and meiotic DSBs, and is also
      activated in cells experiencing DNA replication stress. The Mre11 complex's role
      in recombinational repair primarily concerns the promotion of homologous
      recombination (HR), but it is also implicated in non-homologous end joining
      (NHEJ)--a DSB repair mechanism prevalent in non-dividing cells. We recently
      characterized deletion of the Mre11 complex member, Rad50, in a number of
      postmitotic and proliferative tissues of the mouse. These studies indicated that
      the complex is dispensable in postmitotic tissues, but loss of Rad50 in
      proliferating cells resulted in accumulation of unrepaired, DNA replication
      dependent lesions. The data suggest that the Mre11 complex is not a major
      contributor to NHEJ and support the interpretation that its role in
      recombinational DNA repair is largely restricted to dividing cells, in which
      repair involving sister chromatids predominates. An exception to this concept is
      manifest in previous work from our laboratory revealing that the mammalian Mre11
      complex promotes meiotic DSB repair, an event involving recombination between
      sister chromatids of homologous chromosomes and taking place in cells not
      undergoing replication. Together these studies highlight the importance of cell
      cycle and cell type specific modulation of the Mre11 complex's repair activities
      in vivo.

PMID- 19395854
TI  - Arginine methylation in interferon signaling: new light on an old story.

PMID- 19395855
TI  - On the origin of cancer-associated fibroblasts.

PMID- 19395856
TI  - NFATc2 Ser170 phosphorylation marks mitosis in development and ES cells.
AB  - NFATc2, also known as NFAT1 or NFATp, is a member of NFAT (calcineurin-dependent
      nuclear factor of activated T cells) family of transcription factors. As one of
      major targets for immunosuppressive drugs, NFATc2 has been studied largely in the
      context of T cell activation and proliferation. Recent evidence suggested that it
      has a broader role in both immune and non-immune systems in regulating cell cycle
      progression. Using a monoclonal antibody developed specifically against phospho
      serine 170 (p-Ser170) of NFATc2, we show here that this phosphorylation marks the
      M phase of cell cycle both during embryonic development and in cultured
      fibroblast and ES cells.

PMID- 19395858
TI  - ERK activation increases nitroprusside induced apoptosis in human melanoma cells
      irrespective of p53 status: role of superoxide dismutases.
AB  - Constitutive ERK activation, superoxide dismutases (SOD) and p53 mutations are
      implicated in modulating tumor apoptotic response. We now investigated whether
      human melanoma survival in response to sodium nitroprusside (SNP) is modulated
      by: (a) stable introduction of a DN-mutant p53; (b) pharmacologically inhibiting
      ERK activation with UO126; (c) addition of exogenous SOD. Nitroprusside releases
      nitric oxide (NO) when intact, or acts in a NO-independent manner via iron and
      residual cyanide after light exposure (lex-SNP). When tested at 300 microM in 72
      h treatments by cytometric live-dead assays, intact SNP caused a 50% lethality
      versus a 30% lethality induced by lex-SNP. No protection from SNP toxicity was
      seen when inhibiting the PI3-kinase pathway with LY294002 or c-Jun NH(2) kinase
      signaling with SP600125. However, pretreatment with UO126 protected from SNP
      mediated cell death including counteracting apoptosis-associated Bax expression
      and PARP cleavage, plus reversing loss of Cu,Zn-SOD. Moreover, addition of
      exogenous SOD also protected cells from SNP toxicity. In spite of the greater
      earlier effects of intact SNP, cells treated with single doses of either intact
      or lex-SNP, revealed about a 90% mortality in longer 120 h treatments, and these
      were also counteracted by UO126 or exogenous SOD. This report is the first to
      show that: constitutive ERK activation characteristic of cancer cells, increases
      a nitroprusside-induced apoptosis modulated by SOD.

PMID- 19395857
TI  - Hypercholesterolemia is associated with hyperactive cardiac mTORC1 and mTORC2
      signaling.
AB  - Nutritional excess and hyperlipidemia increase the heart's susceptibility to
      ischemic injury. Mammalian target of rapamycin (mTOR) controls the cellular
      response to nutritional status and may play a role in ischemic injury. To explore
      the effect of hypercholesterolemia on cardiac mTOR signaling, we assessed mTOR
      signaling in hypercholesterolemic swine (HC) that are also susceptible to
      increased cardiac ischemia-reperfusion injury. Yucatan pigs were fed a high
      fat/high-cholesterol diet for 4 weeks to induce hypercholesterolemia, and mTOR
      signaling was measured by immunoblotting and immunofluorescence in the non
      ischemic left ventricular area. Total myocardial mTOR and raptor levels were
      markedly increased in the HC group compared to the normocholesterolemic group,
      and directly correlated with serum cholesterol levels. mTOR exhibited intense
      perinuclear staining in myocytes only in the HC group. Hypercholesterolemia was
      associated with hyperactive signaling upstream and downstream of both mTOR
      complexes, including myocardial Akt, S6K1, 4EBP1, S6 and PKC-alpha, increased
      levels of cardiac hypertrophy markers, and a trend toward lower levels of
      myocardial autophagy. Hypercholesterolemia can now be added to the growing list
      of conditions associated with aberrant mTOR signaling. Hypercholesterolemia
      produces a unique profile of alterations in cardiac mTOR signaling, which is a
      potential target in cardiac diseases associated with hypercholesterolemia and
      nutritional excess.

PMID- 19395859
TI  - From trans-methylation to cytosine methylation: evolution of the methylation
      hypothesis of schizophrenia.
AB  - The role of methylation in the history of psychiatry has traversed a storied
      path. The original trans-methylation hypothesis was proposed at a time when
      chlorpromazine had been synthesized but not yet marketed as an antipsychotic
      (Thorazine). The premise was that abnormal metabolism led to the methylation of
      biogenic amines in the brains of schizophrenia patients and that these
      hallucinogenic compounds produced positive symptoms of the disease. At the time,
      some psychiatrists were interested in drugs such as mescaline and lysergic acid
      diethylamide that replicated clinical symptoms. They understood that these
      compounds might provide a biological basis for psychosis. The amino acid
      methionine (MET) was given to patients in the hopes of confiriming the
      transmethylation hypothesis. However with time, many realized that the hunt for
      an endogenous psychotropic compound would remain elusive. We now believe that the
      MET studies may have produced a toxic reaction in susceptible patients by
      disrupting epigenetic regulation in the brain. The focus of the current review is
      on the coordinate regulation of multiple promoters expressed in neurons that may
      be modulated through methylation. While certainly the identification of genes and
      promoters regulated epigenetically has been steadily increasing over the years,
      there have been few studies that examine methylation changes as a consequence of
      increased levels of a dietary amino acid such as methionine (MET). We suggest
      that the MET mouse model may provide information regarding the identification of
      genes that are regulated by epigenetic perturbations. In addition to our studies
      with the reelin and GAD67 promoters, we also have evidence that additional
      promoters expressed in select neurons of the brain are similarly affected by MET
      administration. We suggest that to expand our knowledge of epigenetically
      responsive promoters using MET might allow for a better appreciation of global
      methylation changes occurring in selected brain regions.

PMID- 19395860
TI  - Conventional radiotherapy or hypofractionation? A study of molecular changes
      resulting from different radiation fractionation schemes.

PMID- 19395861
TI  - Autophagy of whole and partial chloroplasts in individually darkened leaves: a
      unique system in plants?
AB  - Chloroplasts are the characteristic organelle of photoautotrophs. To acquire
      carbohydrates, the majority of leaf nitrogen is distributed to chloroplasts as
      photosynthetic proteins. During age-related senescence or under starvation
      conditions, chloroplasts become a major source of carbon and nitrogen for
      recycling. While bulk degradation of the cytosol and organelles must occur by
      autophagy in plants, the role of autophagy in chloroplast degradation is still
      unclear. Our recent results confirm the role of autophagy in both partial and
      whole chloroplast degradation, at least during promoted senescence of
      individually-darkened leaves.

PMID- 19395862
TI  - Modulation of the activity of methyl binding domain protein 4 (MBD4/MED1) while
      processing iododeoxyuridine generated DNA mispairs.
AB  - DNA glycosylases function to remove endogenous and exogenous base damage and thus
      contribute to the maintenance of genomic integrity. This function gains clinical
      relevance when base mispairs introduced by chemotherapy or radiosensitizing drugs
      become their substrate. This report describes the action of DNA glycosylases on
      the mispairs generated by iododeoxyuridine (IUdR)-a radiosensitizer. A non
      radioactive fluorescent dye-based in vitro glycosylase assay was employed to
      quantitatively measure the enzymatic activities of functionally related DNA
      glycosylases on IUdR generated mispairs including G:IU and A:IU. Thymine DNA
      glycosylase (TDG) and methyl binding domain protein 4 (MBD4/MED1) are found to
      act on G:IU (but not A:IU) mispairs and are functionally complementary to each
      other. However, uracil DNA glycosylase (UDG) does not show any activity on these
      mispairs. The methyl binding domain of MBD4/MED1 was found to specifically
      inhibit the activity of MBD4/MED1 as well as the glycosylase domain, when the
      G:IU mispairs were located in a methylated CpG context. However, inhibition of
      TDG activity on methylated G:IU mispairs by the methyl binding domain was not
      observed.

PMID- 19395863
TI  - Pharmacological inhibition of aurora-A but not aurora-B impairs interphase
      microtubule dynamics.
AB  - Aurora kinases are key cell cycle regulators and represent attractive new targets
      in cancer therapy. In this work we investigated the effect of specific inhibition
      of Aurora-A and Aurora-B on interphase microtubule dynamics using the GSK6000063A
      and AZD1152 HQPA compounds respectively. We show that Aurora-A inhibition results
      in microtubule network disorganization and bundling. Using video microscopy and
      laser-based photo ablation we demonstrate that Aurora-A inhibition decreases
      microtubule shrinkage, growth rate, frequency rescue and nucleation. These
      results open new perspectives on the role of Aurora-A in interphase and might be
      worth considering in a pharmacological perspective.

PMID- 19395864
TI  - Conserved and variable domains of RNase MRP RNA.
AB  - Ribonuclease MRP is a eukaryotic ribonucleoprotein complex consisting of one RNA
      molecule and 7-10 protein subunits. One important function of MRP is to catalyze
      an endonucleolytic cleavage during processing of rRNA precursors. RNase MRP is
      evolutionary related to RNase P which is critical for tRNA processing. A large
      number of MRP RNA sequences that now are available have been used to identify
      conserved primary and secondary structure features of the molecule. MRP RNA has
      structural features in common with P RNA such as a conserved catalytic core, but
      it also has unique features and is characterized by a domain highly variable
      between species. Information regarding primary and secondary structure features
      is of interest not only in basic studies of the function of MRP RNA, but also
      because mutations in the RNA give rise to human genetic diseases such as
      cartilage-hair hypoplasia.

PMID- 19395865
TI  - A central role for autophagy in Alzheimer-type neurodegeneration.
AB  - The macroautophagy (autophagy) pathway is thought to be involved in a variety of
      neurodegenerative diseases, including Alzheimer disease (AD). It is not clear
      however, if autophagy plays a causative role, a protective role or is a
      consequence of the disease process itself. Using a Drosophila model of neuron
      limited expression of AD-associated amyloid beta (Abeta) peptides, we have
      demonstrated an autophagy-mediated neurodegenerative cascade that is initiated by
      Abeta(1-42) and enhanced by aging. Our results suggest a central role for the
      autophagy pathway in AD type neurodegeneration and a new framework to understand
      seemingly unrelated AD phenotypes.

PMID- 19395866
TI  - Immune approaches to treating osteosarcoma.

PMID- 19395867
TI  - LSD1 demethylates histone and non-histone proteins.
AB  - One of the key breakthroughs in the epigenetics/chromatin field in the last
      several years was the identification of enzymes capable of removing the methyl
      group from methylated lysines in histone proteins. Lysine-specific demethylase 1
      (LSD1) was the first such enzyme identified, which has been shown to demethylate
      histone H3 on lysine 4 (H3K4) and lysine 9 (H3K9). LSD1 is essential for
      mammalian development and likely involved in many biological processes. Recent
      studies show that LSD1 demethylates p53 and Dnmt1 and regulates their cellular
      functions, indicating that LSD1 fulfills its biological functions by directly
      acting on both histone and non-histone proteins. LSD1 contains several defined
      domains and associates with a number of protein complexes. Interacting partners
      of LSD1 may play key roles in determining/modulating the activity and specificity
      of LSD1.

PMID- 19395868
TI  - Safety and immunogenicity of an indigenously developed Haemophilus influenzae
      type b conjugate vaccine through various phases of clinical trials.
AB  - In view of the need for a cost effective Haemophilus influenzae type b (Hib)
      conjugate vaccine, a lyophilized vaccine as capsular polysaccharide (PRP)
      conjugated to tetanus toxoid (Sii HibPRO) was indigenously developed by Serum
      Institute of India Ltd., Pune (SIIL). From 2004-07, this new vaccine underwent a
      series of clinical studies before its licensure by National Regulatory Authority
      (NRA). This paper discusses the results obtained during the clinical development
      of this vaccine. On finding the vaccine to be safe in animal toxicity studies, a
      Phase I single dose study was carried out to assess the safety profile of Sii
      HibPRO in healthy adult male volunteers. Subsequently, in Phase III pre-licensure
      study, immunogenicity and safety of Sii HibPRO was assessed and compared with Hib
      tetanus conjugate vaccine (Act-HIB) of Aventis, France. Immunogenicity was
      evaluated based upon serum anti-PRP IgG antibody concentrations by ELISA at
      prevaccination and one month each after the second and third dose. Safety was
      evaluated by recording details of adverse events after each dose of the vaccine.
      Postvaccination after the third dose, there was 100% seroprotection (anti PRP IgG
      titre >or= 0.15 microg/ml) in both the groups. Long term protection (>or=1
      microg/ml) was achieved in 95.2% and 98.06% infants in Sii HibPRO and Act-HIB
      groups, respectively. At 15 months, prior to booster dose, 30 children in each
      group were evaluated and all were found to be seroprotected. Post booster, all of
      them responded with a strong boost response. Safety of Sii HibPRO was re
      established in the post marketing surveillance in which 2,739 doses were
      administered to 1,029 infants, in 23 cities across India.

PMID- 19395870
TI  - Implications of autophagy in anthrax pathogenicity.
AB  - The etiological agent for anthrax is Bacillus anthracis, which produces lethal
      toxin (LT) that exerts a myriad of effects on many immune cells. In our previous
      study, it was demonstrated that LT and protective antigen (PA) induce autophagy
      in mammalian cells. Preliminary results suggest that autophagy may function as a
      cellular defense mechanism against LT-mediated toxemia. This degradation pathway
      may also be relevant to other aspects of the immune response in both innate and
      adaptive immunity. Understanding the role of autophagy in response to anthrax
      infection and the possibility of modulating this degradation pathway as potential
      countermeasures are subjects for further investigation.

PMID- 19395869
TI  - Dual targeting of EphA2 and FAK in ovarian carcinoma.
AB  - EphA2 gene silencing has been shown to result in antitumor efficacy. Here we
      considered whether silencing additional targets downstream of EphA2 would further
      enhance the therapeutic effect. EphA2 targeted siRNA was tested in combination
      with either FAK or Src targeted siRNA using DOPC nanoliposomes in orthotopic
      models of ovarian carcinoma. The effects of therapy were determined by changes in
      tumor weight, proliferation (Ki-67), and microvessel density (CD31). In our
      initial in vivo study, EphA2 plus FAK silencing resulted in the greatest
      reduction in tumor growth (by 73%, p < 0.005) as compared to control siRNA alone.
      In the SKOV3ip1 and HeyA8 ovarian cancer models, EphA2 siRNA-DOPC treatment
      resulted in a 50-67% decrease in tumor growth (p < 0.02, for both), and FAK siRNA
      DOPC resulted in a 61-62% decrease in tumor growth (p < 0.009, p < 0.05,
      respectively). EphA2 plus FAK siRNA-DOPC treatment resulted in a significant
      reduction (SKOV3ip1: 76%, p < 0.007, HeyA8: 90%, p < 0.003) in tumor growth
      compared to control siRNA-DOPC. Combination treatment with EphA2 + FAK siRNA-DOPC
      resulted in significant decreases in tumor cell proliferation (p < 0.001) and
      microvessel density compared to control siRNA-DOPC (80%; p < 0.001), or the
      monotherapy groups (p values <0.001). These data suggest that the antitumor
      efficacy of in vivo EphA2 targeting is enhanced in combination with FAK
      silencing. Dual targeting of EphA2 and FAK may have therapeutic implications for
      ovarian cancer management.

PMID- 19395871
TI  - Pathogenesis of rheumatoid arthritis and c-Fos/AP-1.
AB  - c-Fos/AP-1 controls the expression of inflammatory cytokines and matrix-degrading
      matrix metalloproteinases (MMPs) important in arthritis via promoter AP-1 binding
      motif. Among inflammatory cytokines, IL-1beta is the most important inducer of a
      variety of MMPs, and mainly responsible for cartilage breakdown and
      osteoclastogenesis. IL-1beta and c-Fos/AP-1 influence each other's gene
      expression and activity, resulting in an orchestrated cross-talk that is crucial
      to arthritic joint destruction, where TNFalpha can act synergistically with them.
      While how to stop the degradation of bone and cartilage, i.e., to control MMP,
      has long been the central issue in the research of rheumatoid arthritis (RA),
      selective inhibition of c-Fos/AP-1 does resolve arthritic joint destruction.
      Thus, the blockade of IL-1beta and/or c-Fos/AP-1 can be promising as an effective
      therapy for rheumatoid joint destruction in addition to the currently available
      TNFalpha blocking agents that act mainly on arthritis.

PMID- 19395872
TI  - Rapamycin inhibits mTORC1, but not completely.
AB  - Rapamycin is widely used as a complete inhibitor of the mTORC1 nutrient-sensitive
      signaling complex. Using a novel ATP-competitive inhibitor named Torin1, we have
      found that many mTORC1 functions that regulate cap-dependent translation and
      autophagy are resistant to inhibition by rapamycin.

PMID- 19395873
TI  - Post-transcriptional regulation in lymphocytes: the case of CD154.
AB  - The control of mRNA decay is emerging as an important control point and a major
      contributor to gene expression in both immune and non-immune cells. The
      identification of protein factors and cis-acting elements responsible for
      transcript degradation has illuminated a comprehensive picture of precisely
      orchestrated events required to both regulate and establish the decay process.
      One gene that is highly regulated at the post-transcriptional level is CD40
      ligand (CD154 or CD40L). CD154 on CD4(+) T cells is tightly controlled by an
      interacting network of transcriptional and post-transcriptional processes that
      result in precise surface levels of protein throughout an extended time course of
      antigen stimulation. The activation-induced stabilization of the CD154 transcript
      by a polypyrimidine tract-binding protein (PTB)-complex is a key event that
      corresponds to the temporal expression of CD154. In this review, we discuss known
      and potential roles of major mRNA decay pathways in lymphocytes and focus on the
      unique post-transcriptional mechanisms leading to CD154 expression by activated
      CD4(+) T cells.

PMID- 19395874
TI  - Phosphorylation of Beclin 1 by DAP-kinase promotes autophagy by weakening its
      interactions with Bcl-2 and Bcl-XL.
AB  - Beclin 1, an essential autophagic protein, is a BH3-only protein that binds Bcl-2
      anti-apoptotic family members. The dissociation of Beclin 1 from the Bcl-2
      inhibitors is essential for its autophagic activity, and therefore is tightly
      controlled. We recently revealed a novel phosphorylation-based mechanism by which
      death-associated protein kinase (DAPk) regulates this process. We found that DAPk
      phosphorylates Beclin 1 on T119, a critical residue within its BH3 domain, and
      thus promotes Beclin 1 dissociation from Bcl-X(L) and autophagy induction. Here
      we report that T119 phosphorylation also reduces the interaction between Beclin 1
      and Bcl-2, in line with the high degree of structural homology between the BH3
      binding pockets of Bcl-2 and Bcl-X(L) proteins. Our results reveal a new
      phosphorylation-based mechanism that reduces the interaction of Beclin 1 with its
      inhibitors to activate the autophagic machinery.

PMID- 19395875
TI  - ADAM17 promotes breast cancer cell malignant phenotype through EGFR-PI3K-AKT
      activation.
AB  - A disintegrin and metalloproteinase-17 (ADAM17) is involved in proteolytic
      ectodomain shedding of several membrane-bound growth factors and cytokines. The
      expression and activity of ADAM17 increase under some pathological conditions
      such as stroke and glioma. ADAM17 promotes neural progenitor cell migration and
      contributes to stroke-induced neurogenesis after stroke and brain tumor growth
      and invasion. In the present study, we sought to elucidate whether ADAM17
      contributes to breast cancer progression and its mechanisms. To this end, we
      examined the role of ADAM17 in the proliferation, invasion and tube formation of
      MDA-MB-231 breast cancer cells in vitro. Stable transfection of the MDA-MB-231
      cell line with either a plasmid for overexpression of human ADAM17, or a siRNA to
      ADAM17 was employed in this study to establish high or low ADAM17 expression in
      breast cancer cells, respectively. For study of mechanism, the ADAM17 inhibitor
      TAPI-2 and the PI3K-AKT inhibitor LY294002 were used to counteract high ADAM17
      expression or the activated PI3K-AKT pathway. Proliferation of MDA-MB-231 breast
      cancer cells were tested by MTT, Bromodeoxyuridine incorporation assay, growth
      curve and sulforhodamine B assay. Matrigel invasion assays were used to assess
      the ability of MDA-MB-231 cells to penetrate the Extra Cellular Matrix. A
      Matrigel tube formation assay was performed to test capillary tube formation
      ability. EGFR-PI3K-Akt pathway activation in MDA-MB-231 cells under different
      ADAM17 expression levels were tested by western blot and ELISA. Our data show
      that ADAM17 promotes the MDA-MB-231 malignant phenotype by increased
      proliferation, invasion and angiogenesis. TGFalpha, VEGF secretion and VEGF
      expression was increasing by ADAM17 and counteracted by ADAM17 siRNA, TAPI-2 and
      LY294002 in MDA-MB-231 cells. ADAM17 activated, whereas ADAM17 siRNA, TAPI-2 and
      LY294002 deactivated the EGFR-PI3K-AKT signal pathway, which correlated with MDA
      MB-231 cell malignant phenotype changes. This study suggests ADAM17 contributes
      to breast cancer progression through activation of the EGFR-PI3K-AKT signal
      pathway.

PMID- 19395876
TI  - Merkel cell carcinoma: review.
AB  - Merkel cell carcinoma (MCC) is synonymous with primary cutaneous neuroendocrine
      carcinoma. It tends to affects elderly whites, but there is also an increased
      incidence among immunosuppressed patients. The recent identification of a novel
      polyomavirus associated with the tumor has stimulated renewed interest in its
      pathogenesis. MCC tends to show classic histologic features of a neuroendocrine
      carcinoma and is often positive for CK20, but nonclassic cytologic findings and
      unusual immunophenotypes may be observed and can lead to a diagnostic confusion.
      MCC needs to be distinguished from other primary cutaneous tumors with a small
      cell appearance and metastatic tumors. Surgical excision is the treatment of
      choice, but radiation therapy has also found to be effective. Sentinel lymph node
      biopsy has become an integral part of the staging of patients with MCC.

PMID- 19395877
TI  - The discovery of common recurrent transmembrane protease serine 2 (TMPRSS2)
      erythroblastosis virus E26 transforming sequence (ETS) gene fusions in prostate
      cancer: significance and clinical implications.
AB  - Recurrent gene fusions and chromosomal rearrangements were previously thought to
      be the primary oncogenic mechanism of hematological malignancies and sarcomas.
      The recent discovery of recurrent gene fusions in a majority of prostate cancers
      represents a paradigm shift in understanding the molecular mechanisms of one of
      the most prevalent epithelial malignancies, with important clinical and biologic
      implications. The prostate cancer gene fusions that have been identified so far
      are characterized by 5'-genomic regulatory elements, most notably the androgen
      controlled prostate specific gene, transmembrane protease serine 2, fused to
      members of the erythroblastosis virus E26 transforming sequence family of
      transcription factors, most notably ERG, leading to the overexpression of
      oncogenic transcription factors. The erythroblastosis virus E26 transforming
      sequence gene fusions most likely define a distinct class of prostate cancer with
      potential implications for early diagnosis, prognosis, and rational therapeutic
      targeting. In this review, we summarize the bioinformatics approach that led to
      the discovery of gene fusions, the current state of the frequency, and diversity
      of gene fusions that define the molecular heterogeneity of prostate cancer, their
      associations with prostate cancer progression and clinical outcome, the
      subsequent morphological characteristics, and the potential application of gene
      fusions as biomarkers in the diagnosis and management of prostate cancer.

PMID- 19395878
TI  - Selected topics in the evaluation of pediatric gastrointestinal mucosal biopsies.
AB  - The practice of pediatric gastrointestinal pathology provides specific challenges
      to the pathologist. Often the clinical information accompanying a biopsy specimen
      will read simply, "failure to thrive." Other situations, such as the evaluation
      of a neonate's rectal suction biopsy for Hirschsprung disease, are notorious for
      providing diagnostic challenges in high-pressure situations. In this review, we
      will discuss several commonly encountered situations in pediatric pathology: the
      evaluation of pediatric esophageal eosinophilia, a child who has swallowed a non
      food item, caustic substance, or hot liquid, the evaluation of a pediatric
      colorectal biopsy with focal active colitis, and the evaluation of rectal suction
      biopsies for Hirschsprung disease. With each topic, we will discuss a general
      approach to the case, diagnostic tips, and how to avoid commonly encountered
      pitfalls. Finally, we highlight key references pertinent to these issues that can
      he used to help convey pathologic findings to pediatric gastroenterologists.

PMID- 19395879
TI  - Diagnosing gastroesophageal reflux disease: the pathologist's perspective.
AB  - Gastroesophageal reflux disease (GERD) is a common disease frequently encountered
      by surgical pathologists. Although the pathogenesis and clinical features of the
      disease have been studied for years, many unanswered questions remain. Typical
      clinical symptoms along with the endoscopic findings, pH monitoring, and
      biopsies, all support the diagnosis. However, these tests may yield conflicting
      findings, and at present there is no gold standard for the diagnosis of GERD. In
      patients with normal or nearly normal endoscopic findings (nonerosive reflux
      disease), the major diagnostic burden lies with the histology. The histologic
      diagnosis of GERD is based on a combination of findings, including basal cell
      hyperplasia, papilla elongation, inflammation, and dilatation of intercellular
      spaces. However, these features exhibit varying sensitivity and specificity, and
      minimal biopsy criteria for the diagnosis of reflux esophagitis have not been
      rigorously tested in well-characterized patient populations. However, given the
      high prevalence of GERD, pathologists face esophageal mucosal biopsies daily and
      must recognize the diagnostic strengths and limitations of histologic features of
      reflux esophagitis. Future studies and new techniques may improve the diagnostic
      strength of histology and establish meaningful minimal criteria for the diagnosis
      of reflux esophagitis.

PMID- 19395880
TI  - Minimally invasive adenocarcinomas of the lung.
AB  - Current World Health Organization (WHO) classification of lung adenocarcinomas
      includes noninvasive bronchioloalveolar carcinoma (BAC) and several patterns of
      invasive adenocarcinoma. The most common is a mixed subtype of adenocarcinoma.
      This group is very heterogenous and includes a wide spectrum of tumors ranging
      from adenocarcinomas with a dominant BAC growth pattern (lepidic growth) to
      frankly invasive adenocarcinoma with no BAC component. There is a tendency among
      clinicians to regard tumor as BAC if any significant amount of lepidic growth
      pattern within the tumor is identified. The change in WHO definition of BAC and
      introduction of mixed subtype of adenocarcinoma resulted in disconnect between
      surgical pathologists and clinicians regarding the use of terminology and
      criteria for diagnosis of BAC and mixed subtype of adenocarcinoma. It is clear
      that pure BAC is an extremely rare tumor, whereas mixed subtypes of
      adenocarcinomas may have various clinical presentations and outcomes. The
      mounting evidence suggests that a subset of mixed subtype of adenocarcinomas with
      areas of BAC and focal invasion probably represent more indolent tumors. On the
      basis of the published data, there is a proposal to define a subcategory of
      "minimally invasive adenocarcinoma" of the lung. Many morphologic factors seem to
      play a role in predicting the behavior of these tumors. Depending on the results
      of ongoing clinical trials, surgical management of these tumors may change in a
      near future.

PMID- 19395881
TI  - Multiple spontaneous liver cell adenomas of different types (liver adenomatosis).
AB  - In 1999, Nguyen et al divided focal nodular hyperplasia (FNH) in 2 groups, the
      classical and nonclassical. The former also included those cases of FNH with
      classical characteristics exhibited "on a subtle scale," whereas the latter
      included among others mainly the telangiectatic FNH (T-FNH) variant.
      Hepatocellular adenoma (HCA) was classically considered by definition a neoplasm
      with no ductal or ductular differentiation, but today the spectrum of HCA does
      include variant 3, which may have CK7+ ductules. Owing to genotypic-phenotypic
      correlation, T-FNH (synonymous with progressive FNH of others) is not considered
      yet as part of the spectrum of FNH, instead it is diagnosed as a variant of HCA,
      which now includes 4 variants. Variant-3, which may contain CK7+ ductules, and is
      also termed HCA with ductal/ductular differentiation, corresponds to T-FNH.
      Notwithstanding the nosologic advancement, and outside the "archetypal" types,
      the differential morphologic diagnosis of spontaneous HCA versus FNH may remain
      problematic as ductular proliferation in some cases of FNH may be scanty and hard
      to find. In some histologic overlapping cases of FNH and HCA the morphologic
      diagnosis may be very difficult or even impossible (especially in small lesions)
      and molecular biology may be of critical assistance. A prototypical case of
      surgically resected multiple spontaneous liver cell adenomas of various types,
      including HCA of T-FNH type and steatotic type, previously interpreted in
      different ways, affecting a young girl, is presented herein.

PMID- 19395885
TI  - Practice competencies front and center.

PMID- 19395886
TI  - Knowledge management and the clinical nurse specialist.

PMID- 19395887
TI  - Fondaparinux: a different weapon in the war on clot: update for the clinical
      nurse specialist.

PMID- 19395888
TI  - Transferable skills and entrepreneurial strategy.

PMID- 19395889
TI  - Management of procedural pain: empowering nurses to care for patients through
      clinical nurse specialist consultation and intervention.
AB  - OBJECTIVE: The purpose of this study was to assess the incidence of pain in
      inpatient and outpatient populations experiencing invasive procedures.
      BACKGROUND: Nursing staff consulted the clinical nurse specialist regarding a
      patient they assessed who was not medicated appropriately and experienced
      significant procedural pain. As a result, a Procedural Pain Task Force was
      created to research the incidence of procedural pain and create evidence-based
      practice protocols. METHODS: A convenience sample of 358 patients undergoing
      diagnostic or therapeutic invasive procedures (surgery excluded) was studied.
      Variables for analysis included demographic data, procedure type, medication, and
      perceived pain before, during, and after the procedures. RESULTS: Patients who
      were not premedicated had lower mean pain scores (mean, 1.81) than patients who
      did receive medication before a potentially painful procedure (mean, 3.64). Age
      was negatively correlated with perceived pain; thus, the greater the patient age,
      the lower the pain score. Sex, premedication, and type of procedure were
      positively correlated with perceived pain scores. Sixty-three subjects reporting
      pain scores of 5 or greater during a procedure were further evaluated.
      CONCLUSIONS: Results were used to develop procedural pain guidelines and a
      physician order set as well as a medication reference grid to assist clinicians
      in the management of procedural pain. Furthermore, nurses were empowered by the
      revised guidelines to advocate for relief of pain based on the nursing
      assessment.

PMID- 19395890
TI  - Depressive symptoms and heart failure: examining the sociodemographic variables.
AB  - PURPOSE: The purpose of this study was to determine the differences in depressive
      symptoms among a sample of heart failure outpatients by examining
      sociodemographic and clinical variables: sex, race, marital status, living
      arrangement/status, heart failure severity, and age. The most frequently reported
      depressive symptoms were also examined. DESIGN: A descriptive, cross-sectional
      design was used. SETTING: Patients were enrolled in a larger research study from
      5 clinics in the Midwest (1 adult primary care medicine clinic, 1 heart clinic,
      and 3 heart failure clinics). SAMPLE: The sample included 150 patients with mean
      age of 61.3 years; 88 (59%) were men, and 62 (41%) were women; 47 (31%) were
      African American, 101 (67%) were white, and 2 (2%) were Asian patients. Forty
      seven percent of the patient sample were New York Heart Association class III.
      Approximately half (51%) of the patient sample were married. METHODS: The Patient
      Health Questionnaire 8 was used to measure depressive symptoms. Heart failure
      severity was assessed using the New York Heart Association classification.
      FINDINGS: Patients with class III and IV had significantly more depressive
      symptoms than patients with class I and II (P < .0001). Age was negatively
      correlated with depressive symptoms scores (P < .0002). There were no significant
      differences in depressive symptoms among the variables of sex, race, marital
      status, or living arrangement. The most frequently reported depressive symptom
      was "feeling tired/no energy." CONCLUSIONS: The findings from this study may
      contribute to the development of a broader knowledge base regarding depressive
      symptoms and its correlates in heart failure and may be used as a foundation for
      further research.

PMID- 19395891
TI  - The clinical nurse specialist and essential genomic competencies: charting the
      course.
AB  - Forging new frontiers is one description for the completion of the Human Genome
      Project (HGP) in 2003. This project produced a human DNA blueprint that is
      revolutionalizing society, changing healthcare, and producing new practice
      standards. With the genome map, scientists are identifying DNA variations that
      transform traditional models of health promotion, disease prevention, disease
      classification, treatment, and symptom management. The HGP is shifting emphasis
      from traditional genetics to an expanded genomic message. Nursing has responded
      to the HGP completion by establishing genomic nursing competencies. In 2005, the
      American Nurses Association (ANA), along with 48 nursing organizations, including
      the National Association of Clinical Nurse Specialists (NACNS), endorsed minimum
      essential genetic/genomic nursing competencies for all registered nurses,
      regardless of education or specialty area. How does the clinical nurse specialist
      (CNS) explore the HGP frontier and integrate essential genomic nursing
      competencies into practice? This article discusses the HGP, the development of
      essential genetic/genomic nursing competencies, and the genomic role of the
      advanced practice CNS. A 1-day genomics program is described as a pilot project
      for integrating competencies in practice and education.

PMID- 19395892
TI  - Demonstrating the effectiveness of an online, computer-based learning module for
      arterial blood gas analysis.
AB  - PURPOSE/OBJECTIVES: To determine the effectiveness of a computer-based learning
      module specific to arterial blood gas (ABG) interpretation. DESIGN: A pretest and
      posttest design was used to assess staff nurses' ability to interpret ABGs before
      and after engaging in a computer-based module. SETTING: Two community hospitals
      in northern Illinois. SAMPLE: Fifty-eight staff nurses completed the online
      learning module and the pretest and posttest measures. METHODS: Subjects
      consented to participate and completed a pretest measure of their knowledge of
      ABG interpretation. Subjects participated in a computer-based learning module on
      ABG interpretation and then completed a posttest. FINDINGS: Staff nurses'
      knowledge increased significantly after viewing the computer-based learning
      module (t = 6.3; P < .001). This improvement was irrespective of experience or
      department. CONCLUSIONS AND IMPLICATIONS: Computer-based, online learning has
      emerged as a means of providing continuing education to nurses. Such a teaching
      strategy helps to overcome barriers pertinent to traditional classroom settings.

PMID- 19395893
TI  - Preserving advanced practice nurse role integrity: One hospital's journey.
AB  - Specialists in nursing have existed since the turn of the century. The term
      denoted a nurse with extensive experience in a particular area of nursing who
      performed with technical expertise. The modern advanced practice nurse (APN) is a
      master's degree-prepared clinical expert who has a high level of expertise in the
      assessment, diagnosis, and treatment of the complex responses of individuals or
      populations to health problems. The APN delivers comprehensive, cost-effective
      care and has a recognized role in the multidisciplinary world of healthcare.
      Despite these advancements, the role of the hospital-based APN is poorly
      understood. Other hospital positions such as "nurse educator" or "nurse
      clinician" add to the role confusion. The APN practice in a large urban hospital
      will be examined. The journey of preserving the role integrity of the hospital
      based APN will be explored.

PMID- 19395896
TI  - Clinical nurse specialist profile. Interview by Jo Ellen Rust.

PMID- 19395894
TI  - Integrated Theory of Health Behavior Change: background and intervention
      development.
AB  - An essential characteristic of advanced practice nurses is the use of theory in
      practice. Clinical nurse specialists apply theory in providing or directing
      patient care, in their work as consultants to staff nurses, and as leaders
      influencing and facilitating system change. Knowledge of technology and
      pharmacology has far outpaced knowledge of how to facilitate health behavior
      change, and new theories are needed to better understand how practitioners can
      facilitate health behavior change. In this article, the Integrated Theory of
      Health Behavior Change is described, and an example of its use as foundation to
      intervention development is presented. The Integrated Theory of Health Behavior
      Change suggests that health behavior change can be enhanced by fostering
      knowledge and beliefs, increasing self-regulation skills and abilities, and
      enhancing social facilitation. Engagement in self-management behaviors is seen as
      the proximal outcome influencing the long-term distal outcome of improved health
      status. Person-centered interventions are directed to increasing knowledge and
      beliefs, self-regulation skills and abilities, and social facilitation. Using a
      theoretical framework improves clinical nurse specialist practice by focusing
      assessments, directing the use of best-practice interventions, and improving
      patient outcomes. Using theory fosters improved communication with other
      disciplines and enhances the management of complex clinical conditions by
      providing holistic, comprehensive care.

PMID- 19395898
TI  - The costs of mental illness.

PMID- 19395899
TI  - 8-year follow-up of the MTA sample.

PMID- 19395900
TI  - A wrinkle in time: from early signs to a diagnosis of autism.

PMID- 19395901
TI  - Anatomical brain magnetic resonance imaging of typically developing children and
      adolescents.

PMID- 19395902
TI  - Heterogeneity and homogeneity across the autism spectrum: the role of
      development.

PMID- 19395904
TI  - Predictors of treatment response in pediatric obsessive-compulsive disorder.

PMID- 19395905
TI  - Stimulant medications and growth.

PMID- 19395907
TI  - From individual lymph nodes to stations and zones: East and West reconciled?

PMID- 19395908
TI  - Low-dose CT screening for lung cancer: trial and error?

PMID- 19395909
TI  - PET imaging in patients with coal workers pneumoconiosis and suspected
      malignancy.
AB  - Positron Emission Tomography (PET) with F-18-fluorodeoxyglucose is commonly used
      in the evaluation of lung nodules; however, there is limited data on the PET
      appearance of coal worker's pneumoconiosis (CWP) and its utility for diagnosing
      lung malignancy in this setting. Six cases of CWP and suspected malignancy are
      reported. Each patient had at least one nodule >1 cm in diameter for a total of
      19 nodules >1 cm. On PET imaging 18 of the 19 nodules were hypermetabolic and
      five of the six patients had at least one nodule that was PET positive. Based on
      pathologic data and clinical follow-up, none of the six patients had any evidence
      of malignancy. In this series, PET imaging was often positive in patents with
      CWP; however, all were false positives with standardized uptake value
      measurements in the range that are typically seen with malignant nodules. Due to
      its high rate of false positives, PET imaging seems to be of limited utility in
      diagnosing malignancy in patients with underlying coal worker's pneumoconiosis.

PMID- 19395910
TI  - Endobronchial lipomas: rare benign lung tumors, two case reports.
AB  - Endobronchial lipoma is a rare benign lung tumor. Here we present two cases. One
      case is the first report of the association of and endobronchial lipoma with a
      hilar lipoma. We discuss the epidemiology, difficulties in establishing the
      diagnosis, and the management of this rare condition.

PMID- 19395911
TI  - Complete and durable response of choroid metastasis from non-small cell lung
      cancer with systemic bevacizumab and chemotherapy.
AB  - Ocular metastasis from lung cancer is uncommon. We report a patient with
      metastatic non-small cell lung cancer who was found to have a metastatic lesion
      in the choroid at the time of presentation. The patient was treated with
      carboplatin, gemcitabine, and bevacizumab. After three cycles of chemotherapy,
      radiologic imaging and ophthalmologic examination demonstrated complete
      resolution of the choroid lesion. This case report demonstrates the durable
      response of choroidal metastasis from non-small cell lung cancer to systemic
      bevacizumab and chemotherapy.

PMID- 19395912
TI  - Primary pulmonary choriocarcinoma presenting with a hemothorax.
AB  - Primary pulmonary choriocarcinoma is an extremely rare condition that is
      difficult to diagnose. In this report, we describe a case of primary pulmonary
      choriocarcinoma that presented with a hemothorax, initially diagnosed as an
      ectopic pregnancy. The patient was treated successfully with surgery followed by
      combination chemotherapy. In rare instances such as this, choriocarcinoma can
      originate in sites outside the genital tract; a thorough and thoughtful
      evaluation will ensure an accurate diagnosis and prompt treatment.

PMID- 19395913
TI  - 2008 Meeting of the National Lung Cancer Partnership: a summary of meeting
      highlights.
AB  - Herein are highlights from National Lung Cancer Partnership's Annual Meeting,
      held May 30, 2008 in Chicago. Aiming to improve the match between lung cancer
      patients and their drug treatments, speakers described potential predictive and
      prognostic biomarkers. Approaches included: (1) in non-small cell lung cancer,
      testing for predictive links between tumor expression levels of DNA synthesis
      (RRM1) and repair (ERCC1) enzymes and response to gemcitabine and cisplatin
      respectively, and looking for a prognostic link with ERCC1 expression; (2)
      validating a predictive "meta-gene profile" from gene expression microarray
      studies to distinguish drug-responsive from unresponsive lung cancer tumors; and
      (3) developing proteomics profiling to distinguish lung cancer patients,
      including squamous and nonsquamous cell carcinoma patients, who respond to
      epidermal growth factor receptor tyrosine kinase inhibitors from those who do
      not. The notion that cancer stem cells are fundamental in the development and
      progression of solid tumors including lung cancers was also discussed. Potential
      strategies for using this information to identify useful targets for next
      generation therapies were suggested.

PMID- 19395915
TI  - Is it time to reevaluate the role of surgery in small cell lung cancer?

PMID- 19395916
TI  - Validation of a reverse transcription-polymerase chain reaction-based five-gene
      signature in non-small cell lung cancer.

PMID- 19395927
TI  - Are your skin-prep and catheter maintenance techniques up-to-date?

PMID- 19395929
TI  - How to protect yourself after body fluid exposure.
AB  - An accidental exposure to blood or other potentially infectious material (OPIM)
      such as cerebrospinal or pleural fluid can be a life changing experience. Among
      the bloodborne and OPIM pathogens are HIV, hepatitis B virus (HBV) and hepatitis
      C virus (HCV). Postexposure prophylaxis (PEP) exists for HBV and HIV, but not for
      HCV, which is the most common chronic bloodborne infection in the United States;
      approximately 3.2 million persons are chronically infected. Fortunately, however,
      exposure to blood or OPIM usually doesn't translate into disease transmission. In
      this article, we'll discuss how you can minimize the risk of disease transmission
      if you or a coworker is accidentally exposed to blood or another potentially
      infectious body fluid. But first, let's review some key definitions.

PMID- 19395931
TI  - Fulfilling a dream of service.

PMID- 19395932
TI  - Patient education series: Head lice.

PMID- 19395933
TI  - Playing it safe with bar code medication administration.
AB  - Do you use a scanner in your medication administration process? Failure to follow
      the correct procedures for verification, administration, and documentation of
      medications is poor practice and may expose you to fraud charges. Avoid patient
      harm and legal pitfalls by taking this advice.

PMID- 19395934
TI  - Acute ischemic stroke: Not a moment to lose.
AB  - Familiarize yourself with recommendations from the latest stroke care guidelines
      so you'll be prepared to respond within the narrow therapeutic window for optimal
      treatment.

PMID- 19395936
TI  - Caring for a patient after mastectomy.
AB  - Breast cancer is the most common cancer in women in the United States, and the
      second leading cause of cancer death in women after lung cancer. In 2008, about
      182,460 women were expected to be diagnosed with either invasive or noninvasive
      breast cancer. Because most breast cancers are diagnosed at an early stage,
      thanks to the success of mammography screening, many women have several treatment
      options. Breast conserving surgery (a lumpectomy or partial mastectomy followed
      by radiation therapy or chemotherapy) is the most common local treatment for
      breast cancer. However, mastectomy, which involves removal of all the breast
      tissue, is still performed in some situations; for example, if the tumor is 5 cm
      or larger, if the tumor is large compared with breast size and a lumpectomy would
      result in a poor cosmetic outcome, if clear margins couldn't be obtained with a
      reexcision of a lumpectomy site, or if the procedure is being done for breast
      cancer risk reduction. A woman undergoing mastectomy will need more nursing care
      than one undergoing lumpectomy, as well as extra emotional support and extensive
      patient education about postoperative care. Let's look at what you'll need to
      know.

PMID- 19395937
TI  - Providing culturally sensitive palliative care.
AB  - Recognizing cultural differences can help you communicate more meaningfully with
      your patient, prevent unnecessary stress, and improve end-of-life care.

PMID- 19395939
TI  - Documenting acute spinal cord injury.

PMID- 19395944
TI  - "A Ticket to Ride" protects patients off the unit.

PMID- 19395945
TI  - How do I care for a patient with diabetic ketoacidosis?

PMID- 19395946
TI  - Aspirin-induced postoperative bleeding.

PMID- 19395949
TI  - Antiretroviral drug-drug interaction considerations for HIV-infected children.

PMID- 19395948
TI  - Efficacy and safety of 1 and 2 doses of live attenuated influenza vaccine in
      vaccine-naive children.
AB  - BACKGROUND: We investigated the efficacy and safety of 1 versus 2 doses of live
      attenuated influenza vaccine (LAIV) in influenza vaccine-naive children aged 6 to
      <36 months. PATIENTS/METHODS: Subjects were randomized to 1 of 4 regimens in year
      1: 2 doses LAIV, 1 dose LAIV, excipient placebo, or saline placebo. In year 2,
      LAIV recipients were to receive 1 dose of LAIV and placebo recipients were to
      receive saline placebo. Because of an unintended treatment allocation error in
      year 2, 1 block of subjects who were randomized to LAIV received saline placebo
      and 1 block who were randomized to placebo received LAIV. RESULTS: In year 1,
      vaccine efficacy versus placebo among recipients of 2 and 1 doses of LAIV was
      73.5% and 57.7%, respectively, against antigenically similar strains. In year 2,
      absolute efficacy of a single dose of LAIV was 73.6% and 65.2%, respectively, in
      recipients of 2 and 1 doses of LAIV in year 1. Year 2 efficacy was 57.0% in
      subjects who received 2 doses of LAIV in year 1 and placebo in year 2. Safety and
      tolerability of LAIV were consistent with previous studies. Reactogenicity was
      similar between placebo groups. Seroconversion rates were significantly higher in
      the 2-dose versus the 1-dose LAIV group in year 1 and in both LAIV groups versus
      placebo in years 1 and 2. CONCLUSIONS: One dose of LAIV provided clinically
      significant protection against influenza in young children previously
      unvaccinated against influenza; 2 doses provided additional protection.
      Protection after 2 doses in year 1 persisted through a second season without
      revaccination. LAIV excipients were not a major contributor to reactogenicity.
      These benefits provide support for increased use of LAIV in children > or =2
      years of age.

PMID- 19395950
TI  - Adversomics: the emerging field of vaccine adverse event immunogenetics.

PMID- 19395951
TI  - Evidence for a lower target blood pressure for people with heart disease.
AB  - PURPOSE OF REVIEW: The review assesses the evidence for the benefit of lower
      blood pressure (BP) targets in hypertension management. RECENT FINDINGS: The
      current consensus target for the treatment of hypertension is a BP of below
      140/90 mmHg for all patients, and a BP of below 130/80 mmHg for those with
      diabetes or chronic kidney disease. Recently added to the list of conditions
      warranting the lower BP target are coronary artery disease and coronary artery
      disease equivalents (stroke, carotid disease, aortic aneurysm, and peripheral
      vascular disease), as well as those individuals with a Framingham Risk Score of
      at least 10%. One theoretical issue with lower BP targets may be the existence of
      a J-shaped curve of BP versus cardiovascular event rate, implying a greater risk,
      especially of myocardial ischemia, of lowering diastolic BP, which is also the
      filling pressure of the coronary arteries, below the lower limit of coronary
      autoregulation. The evidence that this is not a compelling concern is provided by
      animal studies, clinical trials with both surrogate and hard endpoints, and
      epidemiologic data. SUMMARY: There is at present no proof that more aggressive
      treatment is harmful and much indirect evidence that it may be beneficial,
      although the clinical trials that specifically address this question are still in
      progress.

PMID- 19395952
TI  - New antithrombotic agents in acute coronary syndromes.
AB  - PURPOSE OF REVIEW: Acute coronary syndromes still account for high mortality in
      many countries. Antithrombotic therapy represents a cornerstone in the therapy of
      acute coronary syndromes. Recent research has focussed on improving anti-ischemic
      potency and reducing bleeding complications as well as improving predictability
      of antithrombotic efficacy. RECENT FINDINGS: New antithrombotic drugs such as the
      factor Xa antagonists and the direct thrombin inhibitors have been developed and
      evaluated in clinical trials. Fondaparinux and bivalirudin are approved for
      clinical use in acute coronary syndromes. They improve the risk/benefit ratio and
      make routine control of their antithrombotic effect unnecessary. Other agents are
      being developed to further improve and facilitate antithrombotic therapy in acute
      coronary syndromes. SUMMARY: Antithrombotic therapy is essential in acute
      coronary syndrome. New drugs are being developed to enter clinical practice and
      improve efficacy and safety of this therapeutic strategy.

PMID- 19395953
TI  - Resistant hypertension: who and how to evaluate.
AB  - PURPOSE OF REVIEW: Resistant hypertension is found in an important and rapidly
      growing subset of the hypertensive population, and data characterizing this group
      of patients are limited. The purpose of this review is to present the latest
      evidence on resistant hypertension, its risk factors, patient characteristics,
      and approach to diagnosis. We focus on important associations between resistant
      hypertension and primary aldosteronism and with obstructive sleep apnea. RECENT
      FINDINGS: Resistant hypertension comprises 20-35% of the general hypertensive
      population. It is important to ascertain that a patient has true resistant
      hypertension and not merely uncontrolled hypertension. Twenty-four-hour
      ambulatory blood pressure monitoring can reliably rule out a white-coat effect
      and may have prognostic significance in patients with resistant hypertension.
      Patients should be screened for secondary causes of hypertension. Primary
      aldosteronism is common among patients with resistant hypertension, as is
      obstructive sleep apnea. A plasma aldosterone to renin ratio is a useful
      screening tool for primary aldosteronism. Aldosterone has been found to
      accelerate the increase in left ventricular mass in patients with hypertension.
      SUMMARY: Patients with resistant hypertension comprise a unique subset, with risk
      factors and associations that are distinct or pronounced compared with the
      general hypertensive population. It is important to bear these associations in
      mind when dealing with patients with true resistant hypertension.

PMID- 19395954
TI  - Randomized trials of clinical networks in the management of ST-elevation MI: can
      they be performed?
AB  - PURPOSE OF THIS REVIEW: Mortality in ST segment elevation myocardial infarction
      is directly related to the degree of myocardial damage sustained as a result of
      vessel occlusion. It is well established that the temporal window during which
      myocardial salvage may be achieved is limited. RECENT FINDINGS: Prehospital
      thrombolysis, facilitated percutaneous coronary intervention (PCI) and prompt
      transfer to institutions with primary PCI capabilities have all been proposed as
      strategies to augment the temporal window. These different approaches all seek to
      modify the way reperfusion is delivered, as opposed to the manner of restoring
      flow, but have been associated with mixed results. Hence, it has become clear
      that further mortality reductions will require system-based and highly
      coordinated clinical networks. SUMMARY: The extent of the mortality benefit
      associated with the development of an integrated reperfusion network has yet to
      be established. Collection of robust data in the context of a clinical trial may
      be obtained by the random allocation of clinical networks as opposed to
      randomization of patients. Furthermore, such data would be applicable to 'real
      world' clinical practice, as optimal reperfusion could be examined in patients
      whose complex comorbidity would preclude their inclusion in conventional ST
      segment elevation myocardial infarction (STEMI) trials.

PMID- 19395955
TI  - The use of early intervention to prevent postoperative complications.
AB  - PURPOSE OF REVIEW: The incidence of complications following major surgery is
      surprisingly high. Patients who develop complications suffer a reduction in long
      term survival. This review aims to explore recent advances in the management of
      surgical patients aimed at preventing postoperative complications. RECENT
      FINDINGS: Identifying patients prior to surgery who are at risk of a poor outcome
      remains challenging. There are a number of scoring systems to assist clinical
      risk assessment. Recent work has investigated the use of plasma biomarkers for
      perioperative risk prediction. Therapies aimed at reducing complication rates by
      attempting to improve tissue oxygen delivery include goal-directed haemodynamic
      therapy and postoperative noninvasive ventilation. The role of perioperative beta
      adrenoceptor antagonists remains unclear. Other important measures include the
      use of a surgical safety checklist and thromboprophylaxis. SUMMARY: Current
      systems for the identification and treatment of high-risk surgical patients are
      inadequate. Further research is required to establish the optimal approach to the
      identification and management of the high-risk surgical patient.

PMID- 19395956
TI  - Surgery-related risk factors.
AB  - PURPOSE OF REVIEW: The surgical procedure remains the key element in the
      multidisciplinary treatment of a wide variety of degenerative, traumatic,
      tumorous, congenital, and vascular diseases, resulting in an estimated 234
      million surgical interventions worldwide each year. Undesired effects are
      inherent in any medical intervention, but are of particular interest in an
      invasive procedure for both the patient and the responsible physician. Major
      topics in current complication research include perception of key factors
      responsible for complication development, prediction, and whenever possible,
      prevention of complications. RECENT FINDINGS: For many years, the technical
      aspects of surgery and the skills of the surgeon her/himself were evaluated and
      considered as the main sources of surgical complications. However, recent studies
      identified many nontechnical perspectives, which could improve the overall
      quality of surgical interventions. SUMMARY: This article reviews selected,
      recently published data in this field and aims to point out the complexity and
      multidimensional facets of surgery-related risk factors.

PMID- 19395958
TI  - Pertussis in early infancy: disease burden and preventive strategies.
AB  - PURPOSE OF REVIEW: Severe pertussis disease in early infancy remains a
      significant problem, both in developed countries with long-standing pertussis
      immunization programs and in poor countries. We review current understanding of
      the disease burden and potential prevention strategies. RECENT FINDINGS: Even
      with intensive care support, infants with pertussis pneumonia still die, so
      prevention is the key. The source of pertussis in infants under 3 months of age
      is often not clear, but in countries with high childhood immunization coverage,
      the sources are usually adults. Strategies to protect these infants may be
      indirect (timely primary immunization and boosters for older children and adults)
      and direct (mother during pregnancy or infant soon after birth). 'Cocooning' by
      immunizing all potential adult contacts is probably the most effective indirect
      strategy but needs funding and programmatic support for successful
      implementation. Maternal immunization is attractive but unproven and has
      significant practical hurdles. The evidence on immunization at birth is
      conflicting and impact, including interference with response to other infant
      vaccines, is unclear. SUMMARY: Adult booster immunization, either universal or
      targeted (mothers during pregnancy or 'cocoon'), would probably be effective but
      is challenging to implement. If shown to be safe and effective, immunization at
      birth has significant practical advantages. Different strategies (alone or
      combined) may be needed in different settings.

PMID- 19395959
TI  - The role of MD-2 in the opsonophagocytosis of Gram-negative bacteria.
AB  - PURPOSE OF REVIEW: The identification of human Toll-like receptors has
      drastically changed our understanding of host-pathogen interactions. This review
      presents recent data on myeloid differentiation factor 2 (MD-2), a membrane-bound
      and soluble receptor for Gram-negative lipopolysaccharide, and its central role
      in the recognition of Gram-negative bacteria, phagocytosis, and Toll-like
      receptor 4 signalling. RECENT FINDINGS: Phagocytosis is a complex mechanism
      involving a variety of receptors and opsonins. The heterogeneity of phagocytic
      mechanisms allows the optimization of bacteria recognition, phagocytosis, and
      killing. Notably, Toll-like receptors were known to play a role in phagocytosis,
      both by modulating opsonins and phagocytosis receptors' expression and activity,
      and by contributing to bacterial recognition and presentation to host cells.
      Recent data provide additional insight into the function of Toll-like receptors
      and associated proteins. In addition to bacterial recognition and activation of
      inflammatory cascades, MD-2 has been recently shown to be an opsonin for Gram
      negative bacteria and an acute-phase protein. These newly described
      characteristics directly link Gram-negative bacteria recognition, transduction of
      Toll-like receptor 4 inflammatory signalling, phagocytosis and bacterial
      clearance. SUMMARY: Recent progress in the understanding of Gram-negative
      bacteria recognition by host cells as well as physiologic functionality of MD-2
      suggests that MD-2 is a critical compound in host response to pathogens and plays
      a central role in physiologic adaptation to various insults.

PMID- 19395962
TI  - Transendothelial lipoprotein transport and regulation of endothelial permeability
      and integrity by lipoproteins.
AB  - PURPOSE OF REVIEW: Previously, the endothelium was considered as a passive
      exchange barrier of lipoproteins between plasma and extravascular tissues. This
      dogma is challenged by recent findings on a dual relationship between
      lipoproteins and endothelial permeability. RECENT FINDINGS: LDL and HDL as well
      as apolipoprotein A-I pass the intact endothelium through transcytosis by
      processes, which involve caveolin-1, the LDL-receptor, ATP-binding cassette
      transporters A1 and G1 or scavenger receptor BI. Moreover, HDL help the
      endothelium to maintain structural integrity and hence selective permeability for
      biomolecules by keeping interendothelial junctions closed, by inhibiting
      endothelial cell apoptosis and by stimulating endothelial proliferation,
      migration and tube formation as well as the recruitment and differentiation of
      endothelial progenitor cells in damaged parts of the endothelium. Both
      apolipoprotein A-I and sphingosin-1-phosphate mediate many of the protective
      effects of HDL on the endothelium by interacting with endothelial scavenger
      receptor BI and sphingosin-1-phosphate receptors, respectively, and by activating
      intracellular signalling cascades, including the small G protein Rac, src-kinase,
      phosphoinositol 3 kinase, protein kinase B (Akt) and mitogen-activated protein
      kinases. SUMMARY: The endothelium actively controls the trafficking of
      lipoproteins between intravascular and extravascular compartments. In addition,
      lipoproteins affect the integrity and permeability of the endothelium.

PMID- 19395963
TI  - Parathyroid hormone signaling in bone and kidney.
AB  - PURPOSE OF REVIEW: Parathyroid hormone (PTH) maintains a physiological balance of
      calcium and phosphate concentrations by binding to its receptor on the plasma
      membrane of cells in bone and kidney. It signals through multiple pathways,
      including protein kinase A and protein kinase C, although a preference for
      certain pathways is apparent in each organ and function. Here, we will review the
      recent advancements regarding PTH signaling in bone and kidney. RECENT FINDINGS:
      Wnt proteins have been reported as important regulators of bone metabolism in
      both PTH-dependent and independent pathways. Recent studies emphasize its role as
      a mediator of PTH signaling, as PTH treatment increased the expression of wnt4
      and sfrp4 and decreased the expression of Wnt inhibitors such as Sost and
      sclerostin, leading to an increase in Wnt signaling. In kidney, sodium-hydrogen
      exchanger regulatory factor 1, originally known for its role in the retention of
      NaPi-IIa at the apical membrane, was shown to have multiple roles in PTH
      signaling, both as a mediator and regulator. SUMMARY: PTH activates a number of
      different signaling pathways by binding to a single receptor in bone and kidney.
      Recent studies demonstrate the involvement of novel factors as well as additional
      roles for previously identified downstream factors of PTH.

PMID- 19395960
TI  - Using proteomics in perinatal and neonatal sepsis: hopes and challenges for the
      future.
AB  - PURPOSE OF REVIEW: Particularities of the fetal immune response to infection
      cause a heightened inflammatory state that acts synergistically with microbial
      insult to induce damage. Proteomics offers the opportunity for detecting fetuses
      at risk of sepsis and neurological injury. RECENT FINDINGS: Molecular tools (16S
      rRNA) demonstrate that the diversity of microbial agents of intra-amniotic
      infection exceeds what is suspected clinically or is documented by cultures. The
      resulting inflammatory process has the potential to damage the fetus in utero.
      Stepwise algorithms (mass restricted score) have been developed to extract
      proteomic profiles characteristic of amniotic fluid inflammation. The mass
      restricted score includes four proteomic biomarkers: defensin-2, defensin-1,
      S100A12, and S100A8 proteins. Other amniotic fluid biomarkers relevant for
      preterm birth are S100A9 and insulin-like growth factor-binding protein 1.
      S100A12 - ligand for the receptor of advanced glycation end products - has the
      strongest association with histological chorioamnionitis and funisitis. Presence
      of S100A12 and S100A8 in amniotic fluid is predictive of early-onset neonatal
      sepsis and poor neurodevelopmental outcome. SUMMARY: Presence of amniotic fluid
      proteomic biomarkers of inflammation is associated with increased inflammatory
      status of the fetus at birth. Future challenges are to find biomarkers that
      provide insight into molecular mechanisms of chronic fetal and neonatal cellular
      damage and to identify candidates for early neuroprotection strategies.

PMID- 19395964
TI  - Cross-talk among bone cells.
AB  - PURPOSE OF REVIEW: Bone cells such as osteoclasts, osteoblasts, and osteocytes
      'talk' to each other throughout adult life to maintain bone integrity. This
      review highlights frontier areas of research on intercellular communication among
      bone cells. RECENT FINDINGS: Bone cells communicate to regulate the balance
      between bone resorption and bone formation. Recent findings have suggested that
      bone remodeling compartment is critical for osteoclast-osteoblast communication
      during bone remodeling. New molecules and mechanisms for bone cell communication,
      including 'coupling' of bone formation to resorption, have been revealed.
      Osteoclastic regulation of pH within the bone remodeling compartment is a
      mechanism that has been posited to rapidly activate osteoblastic bone formation,
      whereas osteocytes in the bone matrix regulate osteoclasts and osteoblasts on the
      bone surface through the lacuno-canaliculi network. SUMMARY: Differentiation,
      activation, and apoptosis of bone cells are often dependent on the status of
      other types of bone cells. Bone cells in different lineages achieve intercellular
      communication not only by ligand-receptor interactions but also by molecules and
      ions traveling in the extracellular space or across gap junctions, processes that
      depend profoundly on the four-dimensional (space and time) architecture of bone
      tissue.

PMID- 19395966
TI  - The impact of body mass index on assisted reproduction.
AB  - PURPOSE OF REVIEW: Obesity is a worldwide problem. The effect of obesity on the
      outcome of assisted reproductive techniques is quite controversial. RECENT
      FINDINGS: Although there is not an absolute consensus based on evidence, obesity
      may lengthen the duration of ovulation induction, increase the gonadotrophin
      dose, decrease the peak estradiol levels, number of mature follicles and number
      of oocytes retrieved, and increase the cycle cancellation rate. Moreover, obesity
      may have a negative impact on oocyte and embryo quality. Thus, fertilization,
      embryo transfer, implantation and pregnancy rates have been usually found to be
      low in many studies. In addition, oocyte retrieval and embryo transfer procedures
      can be difficult due to obesity itself. Finally, miscarriage rate is found to be
      high. None of the studies related with obesity and assisted reproduction has been
      designed as a randomized controlled trial, yet. Definition of obesity, cause of
      infertility, protocols used for ovulation induction, starting dose for
      gonadotrophins, oocyte and embryo-grading systems are not standardized among the
      studies. Some confounding factors, such as polycystic ovary syndrome status and
      age, are not taken into consideration. SUMMARY: Obesity has a negative impact on
      the outcomes of assisted reproductive techniques.

PMID- 19395967
TI  - Management of renal dysfunction in the liver transplant recipient.
AB  - PURPOSE OF REVIEW: Acute and chronic kidney injury following orthotopic liver
      transplantation (OLT) is associated with increased morbidity and mortality. With
      the increasing longevity of liver transplant recipients, chronic kidney disease
      (CKD) has become an increasingly prevalent complication among long-term
      survivors. This article provides an overview of the literature on suggested risk
      factors for acute and CKD following OLT and a discussion of an approach to their
      medical management. RECENT FINDINGS: In OLT candidates with pretransplant renal
      dysfunction, the use of interleukin-2 receptor blockers or antithymocyte globulin
      induction therapy in conjunction with delayed introduction of calcineurin
      inhibitors may preserve early renal function. In long-term stable OLT recipients
      with established calcineurin inhibitor nephrotoxicity, calcineurin inhibitor
      minimization or withdrawal protocols may halt or ameliorate renal dysfunction
      without compromising patient and graft survival. However, large-scale,
      multicenter, randomized controlled trials are still needed. SUMMARY: The
      occurrence of acute kidney injury is common immediately after OLT, whereas the
      incidence of CKD and end-stage renal disease increases with time. Identifying
      patients at risk for acute kidney injury and CKD following OLT and early
      implementation of measures to preserve, halt, or ameliorate the progression of
      renal dysfunction should be an integral part in the management of OLT recipients.

PMID- 19395968
TI  - Is recurrent hepatitis C worse with living donors?
AB  - PURPOSE OF REVIEW: Early reports suggested that hepatitis C virus (HCV) infection
      recurred with greater severity in recipients of living donor liver
      transplantation (LDLT) compared with recipients of deceased donor liver
      transplantation (DDLT). Consequently, there has been uncertainty in the
      transplant community as to whether to encourage use of live donors for patients
      undergoing transplantation for HCV. This review will present the current data
      regarding whether recurrent HCV is worse with living donors. RECENT FINDINGS:
      More recently published studies have not corroborated the results of earlier
      studies showing inferior graft and patient survival in recipients of LDLT. The
      Adult-to-Adult Live Donor Liver Transplant Cohort Study showed that patient and
      graft survival in HCV-positive LDLT recipients was similar to that in DDLT
      recipients once centers had experience with LDLT. Additionally, studies using
      protocol liver biopsies to assess disease severity found no significant
      difference in the rate of fibrosis progression between recipients of LDLT and
      DDLT. SUMMARY: There is no difference in graft survival or fibrosis progression
      between recipients of LDLT compared with DDLT with follow-up periods up to 5
      years. Available data support the use of LDLT as an additional donor source for
      these patients.

PMID- 19395969
TI  - Injectable immunotherapy: recommendations for safe allergen vial preparation in
      the office setting.
AB  - PURPOSE OF REVIEW: To review the proper technique for preparing allergen vials to
      be used in subcutaneous immunotherapy in the office setting, examine the
      potential for bacterial contamination during mixing and handling and associated
      risk factors and review the data relevant to contamination during vial mixing.
      RECENT FINDINGS: Existing literature on the subject of safe vial preparation
      suggests that the incidence of bacterial contamination of allergen vials is very
      low. Historically, there is no report of bacterial infection for subcutaneous
      immunotherapy using vials prepared in the office setting or otherwise when using
      the proper sterile technique. SUMMARY: In-office compounding of vials is a safe
      practice with literature to support continuing this practice of preparation.

PMID- 19395970
TI  - Laryngopharyngeal reflux: current concepts and questions.
AB  - PURPOSE OF REVIEW: Laryngopharyngeal reflux is a widely recognized disorder. Yet,
      decades after its initial description, debate persists regarding pathophysiology,
      diagnosis, and treatment. This review addresses current literature on
      laryngopharyngeal reflux and identifies areas of controversy and future
      opportunities for research. RECENT FINDINGS: Despite numerous research efforts,
      the diagnosis and treatment of laryngopharyngeal reflux remain elusive and
      unproven. Acid-induced changes in laryngopharyngeal mucosa have been confirmed by
      histologic evidence. However, the implications of this for laryngeal symptoms and
      signs are unclear. Diagnosis remains controversial, confounded by lack of
      standardization and accepted, evidence-based norms. Whereas treatment is
      generally believed by clinicians to be effective in alleviating symptoms and
      signs attributed to laryngopharyngeal reflux, incontrovertible data confirming
      efficacy are scarce. Confounding the issues further, there are numerous studies
      that purport to show that various widely used treatments are not effective,
      although the scientific merit of virtually all of these studies has been
      challenged. SUMMARY: Laryngopharyngeal reflux remains a controversial diagnosis.
      Treatment with proton pump inhibitors persists despite weak evidence supporting
      or refuting their utility, and well designed studies are needed to understand
      diagnosis, treatment, pathyophysiology, and long-term health consequences of
      laryngopharyngeal reflux and its treatment.

PMID- 19395971
TI  - Lung cancer screening update.
AB  - PURPOSE OF REVIEW: Lung cancer is a health problem of global proportions. Despite
      intensive research over many years, the prognosis is still very poor. For the
      surgery to be effective, tumours need to be recognized early. Computed tomography
      (CT) is significantly more sensitive than chest radiograph for identifying small,
      asymptomatic lung cancers. Although low-dose CT screening observational trials
      have demonstrated that survival for all tumour types and sizes detected were
      extremely high, there is no clear evidence that low-dose CT screening reduces
      deaths from lung cancer. Only the results of ongoing randomized controlled trials
      can reveal a real benefit of screening in terms of mortality reduction. RECENT
      FINDINGS: We summarize the protocols and the preliminary results of the lung
      cancer screening randomized controlled trial and the problems linked to the
      detection of suspected early cancer. SUMMARY: Today, we cannot already prove the
      ultimate mortality benefit of lung cancer screening with low-dose CT nor we can
      confirm that this approach is not harmful. We are waiting the final analysis of
      randomized controlled trials for lung cancer mortality. Even if is widely
      accepted that pooling data of randomized controlled trials could be of help to
      get powerful results in terms of mortality reduction in shorter follow-up time,
      this opportunity is still under evaluation.

PMID- 19395972
TI  - Mediastinal staging procedures in lung cancer: EBUS, TBNA and mediastinoscopy.
AB  - PURPOSE OF REVIEW: There is increasing awareness of minimally invasive endoscopic
      techniques for mediastinal staging in lung cancer. Traditionally, cervical
      mediastinoscopy has been utilized. Endobronchial ultrasound-guided fine needle
      aspiration (EBUS) has recently emerged as a potential alternative. RECENT
      FINDINGS: EBUS has sensitivity for lung cancer which is at least equivalent (if
      not superior) to cervical mediastinoscopy. However, cervical mediastinoscopy
      remains superior to EBUS and other techniques in its high negative predictive
      value. More recent data suggest EBUS may have a role in presurgical staging of
      radiologically normal subcentimetre nodes and its negative predictive value may
      be equivalent to surgical staging. Ongoing comparative studies between EBUS and
      cervical mediastinoscopy may well clarify relative performance and cost analyses.
      SUMMARY: Currently, insufficient data are present to recommend replacing cervical
      mediastinoscopy with EBUS for lung cancer staging; the negative predictive value
      of EBUS requires validation. However, EBUS can be recommended for initial staging
      as a minimally invasive option provided negative results are followed by cervical
      mediastinoscopy. This would also allow cervical mediastinoscopy to be reserved
      for re-staging. Conventional transbronchial needle aspiration has a limited role
      only as a first-line staging procedure but may aid diagnosis. In the future, EBUS
      may have a role in presurgical staging of the radiologically normal mediastinum
      and re-staging if prior staging is done by cervical mediastinoscopy.

PMID- 19395973
TI  - Comparison of analgesic effect of tramadol alone and a combination of tramadol
      and paracetamol in day-care laparoscopic surgery.
AB  - BACKGROUND AND OBJECTIVE: To compare the analgesic efficacy of tramadol alone
      (1.5 mg kg(-1)) with a tramadol (1 mg kg(-1)) and paracetamol combination in day
      care laparoscopic patients. METHODS: The analgesic efficacy of intravenous
      tramadol alone (1.5 mg kg(-1)) (group T) was compared with a combination of
      intravenous tramadol (1 mg kg(-1)) and oral paracetamol 1 g (group TP) in 60 day
      care laparoscopic patients in a prospective randomized double-blind clinical
      trial in a tertiary care hospital. Intraoperative haemodynamic responses and
      postoperative visual analogue scores were used to assess the analgesic efficacy.
      RESULTS: Only one patient (in group T) received a single dose of rescue analgesia
      intraoperatively. The highest pain scores were recorded at 30 min postoperatively
      in both groups, and rescue analgesia was needed in eight patients in group T and
      in 13 patients in group TP (P = 0.08). The incidence of moderate-to-severe nausea
      was high in group T (P = 0.001). CONCLUSION: We conclude that reducing the dose
      of tramadol to 1 mg kg(-1) and combining it with paracetamol 1 g orally decreased
      the incidence of side effects of tramadol without reducing analgesic efficacy.

PMID- 19395974
TI  - Low bispectral index values in hydranencephaly.

PMID- 19395975
TI  - Age-related differences in factors associated with cigarette smoking among
      Italian high school students.
AB  - INTRODUCTION: Adolescents' cigarette smoking is related to several factors. The
      aim of this study among high school students was to test the hypothesis that
      factors related to smoking behavior could differ in early (14-16-year-old
      students, younger age group) vs. late (17-21-year-old students, older age group)
      adolescence. METHODS: The smoking behavior of 910 students was evaluated by a
      questionnaire. Students were categorized on the basis of their lifetime smoking
      behavior as never, former, occasional and regular smoker. Data were analyzed
      using Student's t-test, chi-square test and multinomial logistic regression
      analysis. RESULTS: In multinomial logistic regression analysis, variables related
      to adolescents' smoking behavior for both age groups were: positive attitude
      toward smoking (P < 0.001), illicit drug use (younger age group, P < 0.001; older
      age group, P = 0.003), smoking at home with parents (younger age group, P =
      0.038; older age group, P < 0.001) and get drunk at least once (younger age
      group, P = 0.002; older age group, P = 0.026). In the younger age group, a
      significant association was also found between students' smoking behavior and
      having smoked a cigar at least once (P = 0.006) and smoking behavior of the best
      friend of the same sex (P = 0.001), whereas the relationship with the hours spent
      with friends of the opposite sex was of borderline significance (P = 0.058). In
      the older age group, other factors related to adolescent's smoking behavior were
      minimizing health consequences of smoking (P = 0.002) and the hours spent with
      friends of the same sex (P = 0.026). CONCLUSION: Our study demonstrates that, as
      adolescence advances, factors related to smoking behavior can vary.

PMID- 19395976
TI  - Atypical Takotsubo syndrome during anagrelide therapy.
AB  - Anagrelide is a phosphodiesterase III inhibitor utilized in the treatment of
      essential thrombocythemia. Anagrelide can be responsible for positive inotropic
      and chonotropic activity of the cardiovascular system. Moreover, it can induce
      vasospam directly on the epicardial coronary arteries. In the literature, it is
      well reported that this inhibitor can determine serious cardiovascular side
      effects, including congestive heart failure, arrhythmia and acute coronary
      syndrome. We describe the case of a 75-year-old woman who developed a mid
      ventricular Takotsubo syndrome while on anagrelide therapy. Takotsubo
      cardiomyopathy, also known as left ventricular ballooning syndrome, is
      characterized by a reversible ventricular contractile dysfunction with akinesis
      and expansion of apical segments and hyperkinesis of the basal segments.
      Recently, atypical cases with akinesia and dilation of mid-ventricular segment
      and hypercontraction of the apical segments, also called mid-ventricular and
      inverted Takotsubo syndrome, have been described. Even though the pathogenesis of
      Takotsubo syndrome is poorly understood, several mechanisms have been proposed,
      including catecholamine-induced myocardial stunning, and ischemia-mediated
      stunning due to multivessel epicardial or microvascular spasm. We think that in
      our case, the adverse response of anagrelide therapy was determined, by
      accumulated dosage of the drug, through an intensive inotropic stimulation and a
      sympathetic hyperactivation in a vulnerable myocardium. To our knowledge, this is
      one of the first reports of an association between anagrelide therapy and
      Takotsubo cardiomyopathy.

PMID- 19395977
TI  - Impact of multivessel stenting on top of percutaneous revascularization for
      unprotected left main disease in the drug-eluting stent era: insights from the
      Turin registry.
AB  - OBJECTIVE: Drug-eluting stents (DESs) are commonly used in patients with
      unprotected left main (ULM) disease. Although multivessel disease and stenting
      are frequent in this population, pertinent details on short-term and long-term
      outcomes are lacking. SETTING AND PATIENTS: We identified consecutive patients
      with DES treatment for ULM. We distinguished patients presenting isolated ULM
      stenting (group A) from those with additional treatment of at least another major
      vessel (group B). The primary end point was major adverse cardiovascular events
      (i.e. death, myocardial infarction or target vessel revascularization). We
      compared the impact of a DES-only versus a hybrid DES and bare metal stent
      strategy for non-ULM lesions. RESULTS: A total of 189 patients were included, 25%
      in group A and 75% in group B. In-hospital events were similarly favorable
      (cardiac death in 0 and 2%, respectively, P = 0.58). A total of 99% patients were
      followed for a median of 25 months, yielding major adverse cardiovascular events
      in 17 and 37.5% (P = 0.011). Specifically, death occurred in 4 and 8.5% (P =
      0.52), cardiac death in 0 and 7% (P = 0.12), myocardial infarction in 6.5 and 9%
      (P = 0.76) and target vessel revascularization in 4.3 and 22% (P = 0.006).
      Adoption of a systematic DES-only strategy for non-ULM lesions conferred
      significant benefits on major adverse cardiovascular events and repeat non-ULM
      revascularizations in comparison to a hybrid strategy (22 versus 45%, P < 0.001,
      and 9 versus 19%, P = 0.004, respectively), at both bivariate and multivariable
      analyses. CONCLUSION: Multivessel stenting on top of DES implantation for ULM can
      be performed with favorable early results. Systematic DES implantation for both
      ULM and non-ULM lesions is pivotal to maximize clinical results and minimize long
      term recurrences.

PMID- 19395978
TI  - Multislice computed tomography for the evaluation of coronary bypass grafts and
      native coronary arteries: comparison with traditional angiography.
AB  - BACKGROUND: Multislice computed tomography (CT) is a promising new noninvasive
      technique for the detection of atherosclerotic disease within a vessel's wall.
      The present study was designed to assess the diagnostic accuracy of 64-slice CT
      in detecting graft disease and in the evaluation of native vessels distally to
      the grafts. METHODS: Forty consecutive patients with previous coronary artery
      bypass underwent both invasive coronary angiography and 64-slice CT. The CT data
      were acquired over 7-12 s period during a single-breath hold using the Smartprep
      technique. Images were reconstructed using the retrospective modality on a
      synchronized ECG in a time frame of between 40 and 80% of the R-R interval.
      RESULTS: A total of 118 grafts were investigated (80 vein and 38 arterial
      conduits). At CT, 31/38 arterial grafts were classified as patent and free from
      significant lesions, whereas seven appeared diseased (five complete occlusion and
      two significant stenoses along the body of the graft). Out of 80 vein grafts, 52
      appeared free of disease and 28 diseased (23 total occlusion and five critical
      stenosis). An absolute concordance between CT and angiographic findings was
      documented for all arterial and venous grafts (100% diagnostic concordance). The
      accuracy of 64-slice CT in the assessment of distal run-off arteries was 90%.
      CONCLUSION: The 64-slice CT detected with very high accuracy the presence of
      diseased arterial and vein grafts. Moreover, an optimal diagnostic accuracy was
      also documented in the appraisal of native vessels distal to the graft
      anastomoses. On the basis of these results, 64-slice CT can be proposed for the
      study of patients after coronary artery bypass and may represent an effective
      screening technique to select those patients with indications of new
      revascularization.

PMID- 19395979
TI  - Impact of a nurse-driven mobility protocol on functional decline in hospitalized
      older adults.
AB  - The purpose of the study was to determine the impact of a nurse-driven mobility
      protocol on functional decline. A nonequivalent control group design was used;
      the independent variable was mobility protocol and dependent variables were
      functional status and length of stay. Older adults who participated in a mobility
      protocol maintained or improved functional status and had a reduced length of
      stay. Practice implications include an emphasis on ambulation in hospitalized
      older adults.

PMID- 19395980
TI  - Public health financial management competencies.
AB  - The absence of appropriate financial management competencies has impeded progress
      in advancing the field of public health finance. It also inhibits the ability to
      professionalize this sector of the workforce. Financial managers should play a
      critical role by providing information relevant to decision making. The lack of
      fundamental financial management knowledge and skills is a barrier to fulfilling
      this role. A national expert committee was convened to examine this issue. The
      committee reviewed standards related to financial and business management
      practices within public health and closely related areas. Alignments were made
      with national standards such as those established for government chief financial
      officers. On the basis of this analysis, a comprehensive set of public health
      financial management competencies was identified and examined further by a review
      panel. At a minimum, the competencies can be used to define job descriptions,
      assess job performance, identify critical gaps in financial analysis, create
      career paths, and design educational programs.

PMID- 19395981
TI  - Fallopian canal meningocele: report of two cases.
AB  - OBJECTIVE: The purpose of this study is to report 2 rare cases of congenital
      fallopian canal meningoceles. INTERVENTIONS: Magnetic resonance imaging, computed
      tomography (CT) of the temporal bone, CT-cisternogram, and combined transmastoid
      approach with middle fossa craniotomy in 2 patients. MAIN OUTCOME MEASURES:
      Radiologic and operative diagnosis of congenital fallopian canal meningoceles.
      RESULTS: Presentations included spontaneous cerebrospinal fluid (CSF) otorrhea
      and recurrent meningitis with intracranial hypertension. Postoperative
      complications included facial nerve palsy and persistent CSF leaks that
      necessitated ventriculoperitoneal shunt and lumbar drain placement. CONCLUSION:
      Use of CT of the temporal bone in combination with CT-cisternogram may define
      sites of active CSF leak. Intraoperative use of fluorescein may assist
      identification of cranial base defects to lower rates of recurrence, and
      intraoperative use of cranial nerve monitoring can minimize the risk of nerve
      injury during repair.

PMID- 19395982
TI  - Asymmetric hearing loss: rule 3,000 for screening vestibular schwannoma.
AB  - OBJECTIVE: To assess the diagnostic yield of audiograms associated to
      electronystagmography (ENG) for screening vestibular schwannomas (VSs), to
      determine what definition of asymmetric sensorineural hearing loss (ASNHL) fits
      best for the diagnosis of VS, and to determine if cochleovestibular symptoms and
      atherosclerotic potential risk factors play a role in the VS screening. STUDY
      DESIGN: Retrospective chart review in a tertiary care center. METHODS: One
      hundred twenty-two patients were included in the study and divided into 2 groups:
      1) patients presenting a VS (n = 74) and 2) patients without VS (n = 48). They
      had received an audiometry assessment, an ENG, and a posterior fossa magnetic
      resonance imaging (MRI). In addition, a variety of risk factors and clinical data
      were collected. Mean hearing threshold by frequency, mean asymmetries by
      frequency, speech discrimination score (SDS), ENG results, and presence or
      absence of vertigo are studied. Cochleovestibular symptoms and atherosclerotic
      potential risk factors were collected. Characteristics were studied with analysis
      of variance, chi2 test, or a paired t test. A receiver operating characteristic
      curve was obtained. A logistic regression with a step-wise selection based on the
      likelihood ratio was used to identify the best subgroup of predictors of the VS.
      RESULTS: The most revealing data were the mean ASNHL at 3,000 Hz (p < 0.001), the
      interaural SDS asymmetry (p < 0.001), the vestibular deficit (p < 0.049), and the
      absence of vertigo (p < 0.001). The ASNHL at 3,000 Hz was the most representative
      value of all the frequencies and for the SDS asymmetry. Interaural difference of
      15 dB or more at 3,000 Hz is sufficient to consider hearing loss as asymmetric.
      When the cutoff for a positive test was placed at 50% probability, the receiver
      operating characteristic curve shows a sensitivity of 73%. The grade of the tumor
      was also related with the degree of ASNHL at 3,000 Hz. Caloric test does not
      predict the localization or the grade of the VS. Tinnitus and atherosclerotic
      potential risk factors were not considered significantly linked with VS.
      CONCLUSION: To reduce the number of negative MRI performed in the investigation
      of an ASNHL, we propose the "rule 3,000," ASNHL of 15 dB or more at the 3,000-Hz
      frequency. In this case, an investigation with MRI is crucial. If this ASNHL is
      less than 15 dB, we recommend a biannual audiometric follow-up.

PMID- 19395983
TI  - Cavernous malformation of the internal auditory canal: a diagnostic challenge.

PMID- 19395984
TI  - Safety of high-dose corticosteroids for the treatment of autoimmune inner ear
      disease.
AB  - OBJECTIVE: To report the adverse effects associated with prolonged high-dose
      prednisone for the treatment of autoimmune inner ear disease (AIED). STUDY
      DESIGN: Prospective data collected as part of a multicenter, randomized,
      controlled trial for the treatment of corticosteroid-responsive AIED with
      methotrexate. SETTING: Tertiary referral centers. PATIENTS: One hundred sixteen
      patients with rapidly progressive, bilateral sensorineural hearing loss.
      INTERVENTION: All patients completed a 1-month course of prednisone (60 mg/d). In
      Phase 2, 67 patients with improvement in hearing underwent a monitored 18-week
      prednisone taper, resulting in 22 weeks of prednisone therapy at an average dose
      of 30 mg per day. Thirty-three patients were randomized to receive methotrexate
      in Phase 2. Thirty-four patients received prednisone and placebo. MAIN OUTCOME
      MEASURE: Adverse events (AE) in patients treated with prednisone only. RESULTS:
      Of 116 patients, 7 had to stop prednisone therapy during the 1-month challenge
      phase due to AE. Of 34 patients, 5 were unable to complete the full 22-week
      course of prednisone due to AE. The most common AE was hyperglycemia, which
      occurred in 17.6% of patients participating in Phase 2. Weight gain was also
      common, with a mean increase in body mass index of 1.6 kg/m2 (95% confidence
      interval, 0.77-2.3) during the 22-week steroid course. Patients entering Phase 2
      were followed for a mean of 66 weeks. No fractures or osteonecrosis were
      reported. CONCLUSION: Although high-dose corticosteroids are associated with
      known serious side effects, prospective data in the literature are limited. The
      present study suggests that with appropriate patient selection, monitoring, and
      patient education, high-dose corticosteroids are a safe and effective treatment
      of AIED.

PMID- 19395985
TI  - Meningioma causing superior canal dehiscence syndrome.

PMID- 19395986
TI  - Functional evaluation of a cell replacement therapy in the inner ear.
AB  - HYPOTHESIS: Cell replacement therapy in the inner ear will contribute to the
      functional recovery of hearing loss. BACKGROUND: Cell replacement therapy is a
      potentially powerful approach to replace degenerated or severely damaged spiral
      ganglion neurons. This study aimed at stimulating the neurite outgrowth of the
      implanted neurons and enhancing the potential therapeutic of inner ear cell
      implants. METHODS: Chronic electrical stimulation (CES) and exogenous
      neurotrophic growth factor (NGF) were applied to 46 guinea pigs transplanted with
      embryonic dorsal root ganglion (DRG) neurons 4 days postdeafening. The animals
      were evaluated with the electrically evoked auditory brainstem responses (EABRs)
      at experimental Days 7, 11, 17, 24, and 31. The animals were euthanized at Day
      31, and the inner ears were dissected for immunohistochemistry investigation.
      RESULTS: Implanted DRG cells, identified by enhanced green fluorescent protein
      fluorescence and a neuronal marker, were found close to Rosenthal canal in the
      adult inner ear for up to 4 weeks after transplantation. Extensive neurite
      projections clearly, greater than in nontreated animals, were observed to
      penetrate the bony modiolus and reach the spiral ganglion region in animals
      supplied with CES and/or NGF. There was, however, no significant difference in
      the thresholds of EABRs between DRG-transplanted animals supplied with CES and/or
      NGF and DRG-transplanted animals without CES or NGF supplement. CONCLUSION: The
      results suggest that CES and/or NGF can stimulate neurite outgrowth from
      implanted neurons, although based on EABR measurement, these interventions did
      not induce functional connections to the central auditory pathway. Additional
      time or novel approaches may enhance functional responsiveness of implanted cells
      in the adult cochlea.

PMID- 19395987
TI  - Elevated level of tenascin and matrix metalloproteinase 9 correlates with the
      bone destruction capacity of cholesteatomas.
AB  - OBJECTIVES: Bone destruction is a key step in the progression of cholesteatomas.
      Some of the lesions can grow without affecting the surrounding anatomic
      structures, whereas others can cause severe bone destruction despite their
      limited size. This study aims to identify factors that could play important role
      during the invasion of the disease. METHODS: Cholesteatoma tissue samples were
      examined immunohistochemically. Tissue samples were arranged on the basis of bone
      destruction (destructive cholesteatomas [DC] and nondestructive cholesteatomas
      [NDC]). Double-immunofluorescent labeling was performed to detect simultaneously
      1) tenascin (TN) and cytokeratin; 2) matrix metalloproteinase 9 (MMP-9) and TN;
      3) TN and Ki-67. An in situ apoptosis detection kit was used to detect apoptotic
      cells. External auditory canal skin samples were used as control. RESULTS: 1) In
      DCs, more widespread stromal TN labeling was seen compared with NDCs or external
      auditory canal skin samples. 2) More enhanced MMP-9 staining was detected in DCs
      compared with NDCs. 3) The proportion of Ki-67-positive cells in DC samples was
      significantly higher than in NDCs. 4) The percentage of apoptotic cells was
      higher in NDC than in DC samples. CONCLUSION: Our present study demonstrates that
      levels of TN, MMP-9, and proliferative activity are increased in cholesteatomas.
      It has also been shown that increased levels of TN, MMP-9-positive cells, and
      proliferative activity of the lesions, as well as decreased levels of apoptosis,
      can be linked to more aggressive clinical behavior of cholesteatomas. Our
      findings also indicate that TN and MMP-9 can be key molecules of bone destruction
      during cholesteatoma progression.

PMID- 19395988
TI  - Complications and pitfalls of cochlear implantation in otosclerosis: a 6-year
      follow-up cohort study.
AB  - OBJECTIVE: To describe and discuss the midterm complications and pitfalls
      reported in patients with otosclerosis who received a cochlear implant. STUDY
      DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS:
      Fifteen patients who received a cochlear implant for otosclerosis, followed up
      for a minimum of 6 years. Onset of hearing loss occurred at a mean age (+/
      standard deviation [SD]) of 32.6 +/- 8.6 years. Mean duration (+/-SD) of hearing
      loss was 26.8 +/- 7.9 years, and mean age (+/-SD) at implant surgery was 58.7 +/-
      9.5 years. INTERVENTIONS: Before cochlear implantation, hearing thresholds were
      tested, and temporal bone anatomy and otosclerotic lesions were documented by
      high-resolution computed tomography and magnetic resonance imaging. All patients
      were implanted with a Med-El Combi 40 + device and a Standard Electrode Array.
      MAIN OUTCOME MEASURES: The number of inserted electrodes was checked by x-ray.
      After cochlear implantation, hearing skills were tested, fitting parameters were
      recorded, and complications were noted. RESULTS: As the disease progressed, the
      number of electrodes decreased, and the electrical thresholds, maximum comfort
      levels, and electric charge increased; these changes were more evident in the
      middle electrodes. Although facial nerve stimulation rate was lower than
      previously reported (13.3%), it increased during follow-up. Two patients (13.3%)
      had untreatable tinnitus. Nevertheless, all speech discrimination parameters
      improved significantly in all patients. CONCLUSION: Despite the need for special
      fitting strategies and the appearance of complications, facial nerve stimulation,
      and tinnitus, improvements in speech discrimination tests support the use of
      cochlear implantation for patients with otosclerosis.

PMID- 19395990
TI  - Editorial.

PMID- 19395989
TI  - Vestibular end-organ and balance deficits after meningitis and cochlear
      implantation in children correlate poorly with functional outcome.
AB  - OBJECTIVE: Assess vestibular and balance function in meningitis-induced profound
      sensorineural hearing loss (SNHL). STUDY DESIGN: Prospective cohort study.
      SETTING: Tertiary pediatric referral center. PATIENTS: Nine pediatric participant
      with profound SNHL after bacterial meningitis with (8) and without (1) unilateral
      Cochlear implant. MAIN OUTCOME MEASURE(S): Horizontal canal function in response
      to caloric and high-frequency rotation (0.25-5 Hz). Saccular function assessed by
      the vestibular evoked myogenic potential. Static and dynamic balance performance
      on the balance subset of the Bruininsk-Oseretsky Test of Motor Proficiency 2.
      Labyrinthine ossification on computed tomography preimplant, with follow-up
      imaging in a subset (n = 7). RESULTS: Horizontal canal function in response to
      caloric stimulation was abnormal in all children, with 5 of 8 demonstrating
      bilateral areflexia and 3 of 8 having asymmetric hypofunction with better
      function on the implanted side. In response to rotation, horizontal canal
      function was abnormal in all but 1 child (8 of 9). Saccular function, assessed by
      VEMP, was intact in most of the children (5 of 7). Static and dynamic balance
      (Bruininsk-Oseretsky Test of Motor Proficiency 2 scores) were significantly
      poorer in the meningitis group compared with both normal-hearing controls (p <
      0.01) and children with SNHL of variable etiology and Cochlear implant (p <
      0.01). Labyrinthine ossification was present in all cases, with variable extent,
      location, and progression. CONCLUSION: Vestibular function and balance are
      compromised in children with SNHL after meningitis. Whereas vestibular loss seems
      well compensated at low frequency through an overreliance on visual inputs,
      deficits surface during high-frequency rotation, particularly in dark. Saccular
      function seems less susceptible to damage from meningitis. Extent, location, and
      progression of ossification were variable. Despite profound dysfunction on
      objective testing, subjective limitations in functional balance were not
      reported, demonstrating the significant ability of children to compensate for
      even the most severe vestibular losses.

PMID- 19395991
TI  - Poor survival outcome with moderate and severe hypercalcemia in gynecologic
      malignancy patients.
AB  - OBJECTIVE: Determine the incidence of hypercalcemia in gynecologic malignancy
      patients and their survival outcome. DESIGN: Single-institution retrospective
      clinical study. PATIENTS AND METHODS: We used Fisher exact test, Kaplan-Meier
      survival curves, and Cox proportional hazards model to analyze demographic and
      clinical data from gynecologic malignancy patients with hypercalcemia who had
      been treated at The University of Texas M.D. Anderson Cancer Center from
      September 1997 to August 2006. RESULTS: Of the 5260 gynecologic malignancy
      patients, 268 had hypercalcemia (5%). Of the 268, 12 were excluded because of
      hyperparathyroidism or coexisting malignancies; thus, 256 patients were included
      in the study. Most patients (82%) had mild hypercalcemia. Severity of
      hypercalcemia was associated with disease stage (P = 0.0019), use of
      hypercalcemia treatment (P < 0.0001), and survival duration (P < 0.0001). The
      median survival duration of patients who had not been treated for hypercalcemia
      was 432 days compared with 106 days in patients who had been treated. The shorter
      survival duration of treated patients seems to result from their disease status
      and hypercalcemia severity rather than whether they were treated for
      hypercalcemia. CONCLUSIONS: Moderate and severe hypercalcemia is associated with
      poorer survival duration in gynecologic malignancy patients. Early detection and
      treatment of hypercalcemia in these patients may prolong survival. To our
      knowledge, this is the first study of hypercalcemia in patients with general
      gynecologic malignancy.

PMID- 19395992
TI  - Magnetic resonance imaging in gynecological oncology.
AB  - Magnetic resonance imaging (MRI) has become an indispensable tool in the
      assessment of malignant disease. With increasingly sophisticated systems and
      technical advancements, MRI has continued to expand its role in providing crucial
      information regarding cancer diagnosis and management. In gynecological
      malignancies, this modality has assumed greater responsibility, particularly in
      the evaluation of cervical and endometrial cancers. In addition to conventional
      imaging, innovative techniques such as dynamic contrast-enhanced MRI and
      diffusion-weighted MRI show promise in offering early assessment of tumor
      response. This paper reviews the current role of MRI in gynecological cancers and
      highlights the potential of novel techniques in improving patient care.

PMID- 19395993
TI  - Surveillance procedures for patients with cervical carcinoma: a review of the
      literature.
AB  - Cervical cancer is still one of the most common malignancies in women. Treatment
      of cervical cancer is very successful, especially in the early stage. However,
      some patients will experience recurrence. The primary purpose of follow-up
      programs is early detection of recurrence disease that should be more likely to
      be amenable to treatment, thereby improving the clinical outcome. Although, in
      the literature, most studies have shown that the surveillance programs did not
      improve the clinical outcome of patients with diagnosis of recurrence, this
      clinical practice is regarded as traditional management. The use of Papanicolaou
      tests to detect recurrent cervical cancer is not sufficiently justified. The
      assessment of tumor markers such as the squamous cell carcinoma antigen could be
      useful. Imaging techniques are important for the detection and assessment of
      recurrent disease. The role of chest x-rays in detecting asymptomatic recurrence
      in patients treated for cervical carcinoma remains controversial. Detection of a
      new abnormal mass or the changes in the size of a known lesion caused by cancer
      growth and the determination of the extent of recurrence with computed tomography
      and magnetic resonance imaging may provide clinical assistance in the selection
      of optimal therapy. The fluoro-2-deoxy-glucose-positron emission tomography for
      surveillance only show 80% of specificity and accuracy with negative predictive
      value of 100%. Integrated fluoro-2-deoxy-glucose-positron emission
      tomography/computed tomography provides precise anatomic localization of
      suspicious areas and, therefore, a better diagnostic interpretation with a
      possible impact on disease-free survival as well. In conclusion, our review
      confirms the need for prospective studies to compare the effectiveness of
      different follow-up regimens measuring overall survival and quality of life
      parameters as outcomes.

PMID- 19395994
TI  - Evaluation of morbidity of suction drains after retroperitoneal lymphadenectomy
      in gynecological tumors: a systematic literature review.
AB  - INTRODUCTION: The prophylactic use of closed suction drains after retroperitoneal
      lymphadenectomy in the management of gynecologic tumors has been widely used to
      prevent collections of clots or lymph and to avoid infections and postoperative
      fistulas. The improvement of newer surgical techniques, the use of antibiotic
      prophylaxis, and the nonclosure of the peritoneum led to the need to reevaluate
      the use of drains. Retrospective, prospective, and randomized studies did not
      find differences in the postoperative morbidity between the use and nonuse of
      drains. Some studies even suggested worse morbidity with the use of drains.
      OBJECTIVES: To assess the morbidity of the use of drains compared with no drains
      in a systematic literature review with aggregate effect measure (meta-analysis).
      MATERIALS AND METHODS: Between 1966 and August 2007, 3 independent reviewers
      analyzed all studies that assessed the use of drains or no drains through a
      comprehensive literature search of the MEDLINE, EMBASE, and Cochrane Central
      Databases. Statistical analysis was carried out through the RevMan software.
      RESULTS: Of the 285 studies initially reviewed, 11 were selected. Only 4 were
      considered adequate for group analysis, totaling 571 patients. When assessing
      outcomes altogether, namely, fever morbidity, symptomatic lymphocysts, deep vein
      thrombosis, pelvic infection, and fistulas, the relative risk was 1.76 (95%
      confidence interval, 1.04-3.01) and number necessary to harm was 12.2 referring
      to the use of drains. CONCLUSIONS: The prophylactic use of continuous suction
      drains after retroperitoneal lymphadenectomy in the management of gynecologic
      tumors should be avoided.

PMID- 19395995
TI  - Junctional adhesion molecule A [corrected] expression in human endometrial
      carcinoma.
AB  - Junctional adhesion molecule A (JAM-A) is involved in cell-cell contact and tight
      junction formation. Loss of cell adhesion molecules may be associated with high
      histologic grade and invasiveness of endometrial carcinoma. We attempted to
      determine JAM-A expression in human endometrial carcinoma and its correlations
      with pathologic features, stage, and survival. Junctional adhesion molecule A
      expression in human endometrial carcinoma was evaluated by immunohistochemistry.
      In addition, we cultured human well and poorly differentiated endometrial
      adenocarcinoma cell lines, Ishikawa cells, and KLE in 3-dimensional basement
      membrane preparation, and JAM-A expression in these cells was assessed by real
      time reverse transcription-polymerase chain reaction and immunohistochemistry.
      Junctional adhesion molecule A immunostaining intensity was negatively correlated
      with histologic grade (tau = -0.420, P < 0.0001), myometrial invasion (tau = 
      0.306, P < 0.01), and stage (tau = -0.383, P < 0.0001). Low JAM-A immunostaining
      intensity was associated with positive vascular space involvement (P < 0.01).
      Moreover, low immunostain intensity was significantly (P < 0.0001) related to low
      overall survival rate and progression-free survival rate. Additionally, in our 3
      dimensional epithelial cell culture, JAM-A expression in poorly differentiated
      adenocarcinoma was significantly lower than that in well-differentiated
      adenocarcinoma (P < 0.001). Junctional adhesion molecule A expression seems to be
      reduced in high-grade or advanced endometrial carcinoma and may be a prognostic
      factor.

PMID- 19395996
TI  - Estradiol attenuates EGF-induced rapid uPAR mobilization and cell migration via
      the G-protein-coupled receptor 30 in ovarian cancer cells.
AB  - Epidermal growth factor (EGF) stimulates proliferation and migration in ovarian
      cancer cells, and high tumor expression of the EGF system correlates with poor
      prognosis. Epidermal growth factor upregulates urokinase plasminogen activator
      receptor (uPAR) on the cell surface via 3 distinct mechanisms: rapid mobilization
      of uPAR from detergent-resistant domains, increased mRNA, and decreased
      degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane
      estrogen receptor (ER).The objective of this study was to explore the effects of
      17beta-estradiol (E(2)) on uPAR expression and cell migration in ovarian cancer
      cells and further to identify the ER involved.We used 7 ovarian cancer cell
      lines, cell migration assay, cellular binding of (125)I-uPA, cellular degradation
      of (125)I-uPA/PAI-1 complex, enzyme-linked immunosorbent assay for uPAR, solid
      phase enzyme immunoassay for ERalpha, and quantitative polymerase chain reaction.
      Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR
      expression. Specifically, E(2) reduces the very rapid increase of detergent
      extractable uPAR, which occurs within minutes of EGF stimulation and probably
      represents mobilization of uPAR from detergent-resistant domains such as lipid
      rafts. Estradiol influenced neither the amount of uPAR mRNA nor the rate of uPAR
      degradation or solubilization. The nuclear ER antagonists ICI 182780 and
      tamoxifen, which are GPR30 agonists, as well as the specifically constructed
      GPR30 agonist G1, mimicked the effect of E(2) on uPAR expression and cell
      migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced
      mobilization of ligated uPAR from detergent-resistant domains and subsequent
      migration in ovarian cancer cells. The response to various ER ligands indicates
      that this effect is mediated via the membrane ER GPR30.

PMID- 19395997
TI  - Survival after second-line intraperitoneal therapy for the treatment of
      epithelial ovarian cancer: the Gynecologic Oncology Group experience.
AB  - OBJECTIVE: To assess the association between patient-disease characteristics and
      overall survival (OS) after second-line intraperitoneal (IP) treatment of ovarian
      cancer. METHODS: Data were aggregated from 7 Gynecologic Oncology Group (GOG)
      phase 2 studies conducted between 1988 and 1995 to evaluate IP therapy for
      partially responsive or recurrent disease but no tumor masses greater than 0.5
      cm. Factors evaluated include age, performance status, extent of residual
      disease, tumor grade, and histologic diagnosis. RESULTS: A total of 432 eligible
      women were treated on 1 of the 7 second-line phase 2 IP trials. The median OS was
      2.4 years (range of individual study medians, 1.9-2.9 years). Relative to women
      with grade 1 cancers, those with grade 2 or 3 cancers experienced 1.82 (95%
      confidence interval [CI], 1.21-2.74) and 2.02 (95% CI, 1.35-3.03) times greater
      instantaneous death rates, respectively, and those with clear cell adenocarcinoma
      experienced death rates 6.00 (95% CI, 3.27-10.9) times greater. The extent of
      residual disease, surgically assessed before starting study treatment, was also
      associated with OS. Relative to those who had no evidence of gross disease, those
      with gross disease that was completely resected, or with unresectable disease
      (not larger than 0.5 cm), experienced death rates 1.74 (95% CI, 1.25-2.42) and
      2.26 (95% CI, 1.67-3.05) times greater, respectively. CONCLUSIONS: There are
      patient and disease characteristics strongly associated with survival after
      second-line IP treatments. These factors are relevant to clinicians considering
      IP therapy outside the investigative setting and for the development of future
      studies in this area.

PMID- 19395998
TI  - Accuracy of ultrasonography with color Doppler in ovarian tumor: a systematic
      quantitative review.
AB  - A quantitative systematic review was performed to estimate the accuracy
      ultrasonography with color Doppler in the diagnosis of ovarian tumors. Studies
      that compared color Doppler ultrasonography with paraffin-embedded sections
      parameters for the diagnosis of ovarian tumors were included. Twelve studies were
      analyzed, which included 2398 women. The pooled sensitivity was 0.87 (95%
      confidence interval [CI], 0.84-0.90); and the specificity was 0.92 (95% CI 0.87
      0.90). The diagnostic odds ratio for ovarian cancer and borderline lesions vs
      benign lesions was 125 (95% CI, 55-283). Summary receiver operating
      characteristic curves were constructed because of heterogeneity in the diagnostic
      odds ratio. For malignant ovarian cancer and borderline versus benign lesions,
      the area under the curve was 0.9577. In conclusion, ultrasonography with color
      Doppler is a useful preoperative test for predicting the diagnosis of pelvic
      masses.

PMID- 19395999
TI  - Cardiac arrest during laparotomy with argon beam coagulation of metastatic
      ovarian cancer.
AB  - BACKGROUND: The argon beam coagulation (ABC) is a safe and effective tool for
      surgical cytoreduction of metastatic ovarian carcinomas. CASE: A 66-year-old
      woman with newly diagnosed advanced stage epithelial ovarian cancer underwent
      primary cytoreductive surgery involving ABC of tumor implants. Intraoperatively,
      she experienced cardiac arrest during use of the ABC. She was successfully
      resuscitated. The etiology of the arrest was thought to be secondary to a venous
      gas embolism. CONCLUSIONS: The risk associated with venous gas embolism in a
      laparotomy case is exceedingly low. This is the first case report of venous gas
      embolism during ABC in a surgical procedure for gynecologic malignancy. Proper
      monitoring and support services should always be immediately available when using
      ABC.

PMID- 19396000
TI  - Clinical utility of CA-125 for maintenance therapy in the treatment of advanced
      stage ovarian carcinoma.
AB  - Maintenance therapy has been extensively studied to discern any prospective
      therapeutic advantage in the treatment of advanced stage ovarian carcinoma. The
      CA-125 assay may have prognostic benefit in determining whether this treatment
      regimen is appropriate for ovarian carcinoma patients who achieve a complete
      response to first-line therapy. We retrospectively documented the CA-125 levels
      of 2 advanced ovarian cancer patient groups who exhibited a clinically defined
      complete response to their primary induction therapy. Patients were then treated
      with a paclitaxel-based maintenance therapy regimen. The first group (group A; n
      = 13 patients) received 3 cycles of single-agent paclitaxel maintenance therapy,
      and the second group (group B; n = 13 patients) received 12 cycles of single
      agent paclitaxel maintenance therapy. The premaintenance therapy CA-125 serum
      levels (<10 or > or =10 U/mL) of the 2 treatment groups were then retrospectively
      evaluated in an intragroup analysis to discern any relationship with progression
      free survival (PFS) and overall survival. There was a statistically significantly
      relationship between the CA-125 levels (<10 U/mL) premaintenance therapy and PFS.
      The patients who had the lowest CA-125 levels exhibited the most favorable PFS
      results. Despite the limited sample size and nonrandomized nature of this study,
      these results are provocative and suggest that advanced ovarian cancer patients
      who achieve an excellent response to primary platinum-based chemotherapy with a
      CA-125 serum level less than 10 U/mL may be more amenable to the benefits of
      paclitaxel maintenance therapy.

PMID- 19396001
TI  - Diffuse uterine adenomatoid tumor in a patient with chronic hepatitis C virus
      infection.
AB  - Uterine adenomatoid tumors are usually solitary lesions. Adenomatoid tumors
      diffusely infiltrating the entire myometrium have rarely been reported in the
      literature. A feature common to half of the reported cases of diffuse uterine
      adenomatoid tumor was an immunocompromised status of the patient caused by the
      medications for renal transplantation. In this article, we describe an unusual
      case of diffuse uterine adenomatoid tumor in a patient with chronic hepatitis C
      virus infection. Pelvic examination showed an irregular and enlarged uterus.
      Supracervical hysterectomy and bilateral salpingo-oophorectomy was performed with
      a clinical diagnosis of uterine leiomyoma. Pathological examination showed, in
      addition to multiple leiomyomas, diffuse uterine adenomatoid tumor. We suggested
      that the diffuse pattern in our patient might be related to immunosuppression
      secondary to chronic hepatitis C virus infection.

PMID- 19396002
TI  - Clinical outcome of ET-743 (Trabectedin; Yondelis) in high-grade uterine
      sarcomas: report on five patients and a review of the literature.
AB  - The clinical impact of ET-743 (trabectedin; Yondelis) in women with
      leiomyosarcoma and undifferentiated uterine sarcoma in patients previously
      treated with chemotherapy is investigated. Current data show a clinical benefit
      in 2/5 patients, of which 1 had a partial remission during 9 months. Pooling the
      treatment outcomes with literature data, a response in 5 (38%) of 13 patients and
      a clinical benefit in 7 (54%) of 13 patients for all high-grade uterine sarcomas
      is calculated. When only uterine leiomyosarcomas are concerned, response rate is
      5 (45%) of 11 patients with a clinical benefit in 7 (64%) of 11 patients. These
      results on the use of ET-743 in uterine sarcoma patients support the conductance
      of larger trials.

PMID- 19396003
TI  - Efficacy of megestrol acetate (megace) in the treatment of patients with early
      endometrial adenocarcinoma: our experiences with 21 patients.
AB  - BACKGROUND: There are therapeutic dilemmas regarding fertility-preserving
      treatment among young women with well-differentiated endometrial carcinoma.
      MATERIALS AND METHODS: Twenty-one patients with stage IA well-differentiated
      endometrial adenocarcinoma were enrolled in a prospective study. The treatment
      initiated with 160 mg/d of megestrol acetate. The patients underwent dilatation
      and curettage and hysteroscopy after 3 months, and in cases of normal pathology,
      the therapy continued for another 3-month period. In patients who did not respond
      to treatment, the dosage of the drug was doubled (320 mg/d), and the therapy
      continued for another 3 months. At the second time, patients who did not respond
      to treatment were recommended for hysterectomy, and in patients who responded to
      treatment, an additional 3 months of treatment with megestrol acetate (320 mg/d)
      was administered. RESULTS: Our results showed a response rate of 85.71% (18
      patients), and 3 patients underwent hysterectomy. The mean (SD) treatment
      duration was 8.85 (2.00) months (range, 6-12 months). The response to therapy was
      observed in 5 patients (27.78%) with a dosage of 160 mg/d, and the remaining
      patients with 320 mg/d. Pregnancy occurred in 5 patients (27.78%). Recurrence
      happened in 3 (16.67%) of 18 patients who responded to treatment who did not give
      a permit to undergo hysterectomy and received medication again. Two (66.67%) of
      these patients experienced remission again, whereas the other one was candidate
      for hysterectomy. CONCLUSIONS: The results of this study show that, when an
      initial response is not achieved or when disease recurs, use of 320 mg/d seems to
      be associated with a better therapeutic response. Furthermore, serious
      complications were not observed with this dosage.

PMID- 19396004
TI  - Endometrial stromal sarcoma: treatment and patterns of recurrence.
AB  - Our objective was to investigate recurrence patterns and conduct an outcome
      analysis of patients with endometrial stromal sarcoma (ESS).A retrospective
      review yielded 30 patients with ESS (20 low-grade, 10 high-grade) who underwent
      primary surgical resection from 1982 to 2005. Median follow-up was 42 months.All
      patients underwent hysterectomy, whereas pelvic (P) and paraaortic (PA)
      lymphadenectomy were performed in 12 and 7 patients, respectively. A median of 26
      pelvic lymph nodes and 9 PA lymph nodes were removed. Pelvic or PA lymphatic
      disease was noted in 25% and 29% of patients, respectively. Extrauterine disease
      was identified in 11 (45%) of 24 patients undergoing exploratory laparotomy; 6
      had no residual disease after cytoreductive surgery. None of these 6 patients
      experienced abdominal failure, but 1 had a hematological recurrence. Thrombotic
      complications were noted in 13% of patients. The 5-year overall survival was 65%.
      Overall survival was influenced by grade (79% vs 40%, P = 0.03) and extrauterine
      disease (77% vs 32%, P = 0.01). No patient who underwent a systematic
      lymphadenectomy had a lymphatic recurrence, irrespective of nodal status. There
      were 7 (23%) hematological recurrences; 2 in surgical stage I ESS. Two patients
      with low-grade ESS remain without evidence of disease 130 and 210 months after
      secondary cytoreduction. In contrast, no patient with high-grade ESS survived a
      recurrence.There is high prevalence of extrauterine and nodal disease in ESS.
      Patients are at high risk for thrombotic complications. If aggressively staged,
      the predominant failure risk for stage I patients is hematogenous, suggesting the
      need for improved systemic treatments.

PMID- 19396005
TI  - Uterine leiomyosarcoma: does the primary surgical procedure matter?
AB  - BACKGROUND: Uterine leiomyosarcoma (LMS) has a poor prognosis even after early
      stage diagnosis. Because there are no accurate diagnostic tools for
      preoperatively distinguishing LMS from uterine leiomyoma, surgeons might opt for
      partial surgical procedures such as myomectomy or subtotal hysterectomy. We
      sought to determine whether a surgical procedure that cuts through the tumor
      influences prognosis. MATERIALS AND METHODS: Demographic and clinical data of
      consecutive patients with stage I LMS treated between 1969 and 2005 were
      reviewed. The study population was divided into group A: patients whose first
      surgical intervention was total hysterectomy (n = 21); and group B: patients who
      underwent procedures involving tumor injury, for example, myomectomy,
      laparoscopic hysterectomy with a morcellator knife, or hysteroscopic myomectomy
      (n = 16). Survival rates were analyzed and compared. A Cox proportional hazards
      model was used to assess the association between variables of interest and
      prognosis. RESULTS: The median age at diagnosis was 50 years (range, 30-74
      years). Median follow-up duration was 44 months. The 2 groups did not differ
      significantly in age at diagnosis, menopausal status, gravidity, parity,
      postoperative radiotherapy, or time to last follow-up. Kaplan-Meier curves showed
      significantly better survival rates (P = 0.04) and a significant advantage in
      recurrence rate (P = 0.03) for group A compared with group B. Survival in group A
      was 2.8-fold better than that in group B (95% confidence interval, 1.02-7.67).
      These estimates remained stable after adjustment for age, menopausal status, and
      radiotherapy. CONCLUSIONS: In patients with stage I LMS, primary surgery
      involving tumor injury seems to be associated with a worse prognosis than total
      hysterectomy as a primary intervention.

PMID- 19396006
TI  - A clinical and biological comparison between malignant mixed mullerian tumors and
      grade 3 endometrioid endometrial carcinomas.
AB  - OBJECTIVE: To examine the clinicopathologic features, progression-free interval,
      and survival of patients with grade 3 endometrioid endometrial cancer (G3 EEC)
      and malignant mixed mullerian tumors (MMMTs). Akt, epidermal growth factor
      receptor (EGFR), and HER-2/neu expression in these histologic subtypes was also
      investigated. Associations between phosphorylated Akt and clinicopathologic
      features were tested. METHODS: One hundred nineteen women whose conditions were
      diagnosed with MMMT or G3 EEC from January 1, 1990, to December 31, 2003, met
      inclusion criteria. Retrospective data review was performed. In addition, Akt and
      EGFR protein expression was measured in tissue samples using Western blotting and
      immunohistochemistry. Fluorescence in situ hybridization was used to assay HER
      2/neu gene amplification. RESULTS: Fifty-nine patients with MMMT and 60 patients
      with G3 EEC were identified. Patients with MMMT were older (P = 0.055), more
      likely to be African American (P = 0.049), have a family history of breast cancer
      (P = 0.039), have disease involving the uterine cervix (P = 0.007), and
      experience postoperative complications (P = 0.012). Patients with MMMT had a
      significantly shorter progression-free interval (23 vs 57 months, P = 0.001) and
      survival (55 vs 92 months, P = 0.001) than patients with G3 EEC.Grade 3 EEC and
      MMMT have significantly higher phospho-Akt levels than grade 1 EEC and normal
      controls. Phospho-Akt was associated with depth of myometrial invasion (r = 0.46,
      P = 0.05), but not with stage, lymph-vascular space invasion, or tumor size. The
      mesenchymal component of MMMT preferentially demonstrated EGFR expression
      relative to the epithelial component (45% vs 13%, P = 0.06). HER-2/neu
      amplification was observed in 1 of 37 samples. CONCLUSIONS: Improved therapy is
      warranted for both poorly differentiated EEC and MMMT. Recognition of
      similarities and differences between MMMT and other high-grade histologic types
      of uterine cancer may provide rationale for new treatment approaches possibly
      incorporating targeted biological therapies.

PMID- 19396007
TI  - Comparison of human papillomavirus detection and typing by hybrid capture 2,
      linear array, DNA chip, and cycle sequencing in cervical swab samples.
AB  - Although the Hybrid Capture II (HC II) assay can detect 13 high-risk human
      papillomavirus (HPVs), it does not yield any genotype-specific information. We
      evaluated the performance of 4 HPV DNA tests, namely, HC II, Linear Array (LA),
      DNA chip, and cycle sequencing for their capacity to detect the presence of high
      risk HPV DNA and HPV-associated cervical lesions. Seventy-six women who were
      referred to the colposcopy clinic for abnormal cytology were enrolled. The women
      were examined using liquid-based cytology, colposcopy-directed biopsy, and HPV
      DNA tests. After DNA extraction from a single sample, HPV DNA tests were
      performed by all 4 methods on the same specimen. The LA test has higher HPV
      positive rates than HC II for cervical intraepithelial neoplasia I (83.3% vs
      61.1%; P < 0.01) and for cervical intraepithelial neoplasia II and more severe
      lesions (100.0% vs 80.0%; P < 0.01). The concordance between the DNA chip and LA
      tests was 89.5%, confirming substantial agreement (kappa coefficient = 0.73), and
      the concordance between HC II and the DNA chip was 80.3%, also showing
      substantial agreement (kappa coefficient = 0.738). The concordance for 15 high
      risk HPV genotypes between LA and sequencing was 82.5% with a kappa value of
      0.536. Furthermore, the LA test was more sensitive in the detection of high-grade
      cervical lesions than HC II (100% vs 92.3%, P < 0.01). The LA test showed
      superior sensitivity in the detection of clinically relevant HPV infections and
      has proven to be an accurate tool for identifying individual HPV types,
      especially in cases of multiple HPV infections.

PMID- 19396008
TI  - The use of cisplatin to treat advanced-stage cervical cancer during pregnancy
      allows fetal development and prevents cancer progression: report of a case and
      review of the literature.
AB  - BACKGROUND: Cervical cancer is one of the most frequently encountered
      malignancies in pregnancy. For early-stage disease arising in late second/third
      trimester, treatment may be delayed until delivery. However, in advanced disease,
      data are lacking. CASE: A 26-year-old woman presented at 21 weeks gestation with
      a stage IIB high-grade clear cell cervical carcinoma. At 25 + 1 weeks gestation,
      cisplatin 100 mg/m(2) every 21 days was commenced. One month after cycle 3, a
      healthy infant was delivered. Thereafter, further cisplatin, intracavity cesium,
      and chemoradiation were administered. Findings from subsequent clinical
      examination and magnetic resonance imaging were normal. Fifteen months post
      treatment, both patient and baby remain well. CONCLUSION: Neoadjuvant cisplatin
      chemotherapy can be used in stage IIB cervical carcinoma during pregnancy to
      allow fetal development and prevent disease progression before delivery.

PMID- 19396009
TI  - Postoperative adjuvant chemotherapy for node-positive cervical adenocarcinoma.
AB  - We examined the effectiveness of postoperative adjuvant chemotherapy for node
      positive cervical adenocarcinoma. During the period from 1994 to 2002, 98
      consecutive patients with clinical stage I and II cervical adenocarcinoma were
      treated surgically without having undergone any prior treatment. Surgical
      procedures included radical hysterectomy, bilateral salpingo-oophorectomy, and
      pelvic lymphadenectomy. Postoperatively, 21 patients were found to have lymph
      node metastasis, and all were treated with chemotherapy in the absence of
      radiotherapy. All patients were followed up for at least 5 years. Recurrence
      developed in 9 of the 21 patients, all 9 died of the disease. Six of the 9
      recurrences were extrapelvic lesions. Five-year disease-free survival and overall
      survival were 57% and 67%, respectively. Recurrence was more common in patients
      with 6 or more positive nodes than in those with fewer than 3 positive nodes.
      These data suggest the potential role of postoperative chemotherapy for
      treatments of cervical adenocarcinoma. However, the effectiveness of chemotherapy
      alone in node-positive cervical adenocarcinoma was likely not as high as that in
      squamous cell carcinoma. Despite our use of postoperative chemotherapy in the
      absence of pelvic radiation, the disease recurred predominantly at distant sites.

PMID- 19396010
TI  - Estimating the long-term clinical impact of cervical cancer vaccination in
      Taiwan.
AB  - The high burden of human papillomavirus (HPV) infection and subsequent cervical
      cancer in the presence of screening in Taiwan suggests the need for further
      prevention strategies. Epidemiology and screening practices vary considerably
      between countries, and specific analyses are required to estimate the impact of
      HPV vaccination. This study adapted a computer-based health economic model to
      Taiwan to project the clinical impact of the introduction of a prophylactic
      vaccine against persistent HPV 16/18 infection on cervical disease. A Markov
      model based on the natural history of HPV and cervical cancer was developed to
      simulate transitions between health states (normal, HPV, cervical intraepithelial
      neoplasia [CIN] stages I to III, cervical cancer stages I to IV, and death) in
      the presence of screening. The model was calibrated to Taiwan epidemiological end
      points including age-specific HPV prevalence, prevalence of CIN lesions, and
      predicted cervical cancer incidence and mortality. Taiwanese screening and
      treatment practices were modeled, and published clinical trial data were used to
      estimate vaccine efficacy. With 100% vaccine coverage in a 13-year-old cohort of
      females, there is estimated to be a 71% reduction in cervical cancer cases and
      deaths due to all HPV types and substantial reductions in the prevalence of
      precancerous lesions and screening outcomes. Removing the risk of HPV infection
      of a large proportion of Taiwanese females, with a high underlying cervical
      cancer incidence rate, would be expected to have dramatic effects on the health
      care system and mortality in Taiwan.

PMID- 19396011
TI  - Profile of mortality among women with gestational trophoblastic disease infected
      with the human immunodeficiency virus (HIV): argument for a new poor prognostic
      factor.
AB  - Gestational trophoblastic disease (GTD) encompasses a spectrum of conditions
      ranging from hydatidiform mole to choriocarcinoma. The management of GTD in
      association with human immunodeficiency virus (HIV) infection is complicated by
      the interaction between chemotherapy, antiretroviral therapy, and poor
      performance status due to HIV-related illnesses. This study describes the profile
      of mortality of women with GTD in the background of HIV infection. A total of 78
      patients with GTD were reviewed retrospectively. There were 53 patients with
      invasive molar pregnancy and 23 patients with choriocarcinoma. The HIV
      seroprevalence was 31%. There were 15 deaths (19%). There were 8 HIV-infected
      (33%) and 7 HIV noninfected (13%) who demised. Of the 8 patients with CD4 counts
      less than 200 cells/microL, 7 patients demised. There were no mortalities among
      patients with CD4 counts more than 200 cells/microL. Of the 15 deaths, 5 HIV
      infected patients and 5 HIV-noninfected patients received chemotherapy. There
      were 5 patients admitted in very poor general condition precluding the
      administration of chemotherapy. Among the 10 patients that received chemotherapy
      and demised, the causes of death included widespread disease, multiorgan failure,
      and toxicity due to chemotherapy. These findings highlight the poor outcomes of
      HIV-infected women with CD4 counts less than 200 cells/microL due to poor
      tolerance to chemotherapy or poor performance status precluding administration of
      chemotherapy.

PMID- 19396013
TI  - Pilot study on transdiaphragmatic thoracoscopic-assisted pleural biopsy and
      intrathoracic washing cytology for Stage IIIc ovarian cancer with diaphragmatic
      metastases.
AB  - PURPOSE: The significance of investigations of thoracic cavities as well as
      pleural biopsy and intrathoracic washing cytology through transdiaphragmatic
      thoracoscopy for stage IIIc ovarian cancer with diaphragmatic metastases was
      assessed as a prospective pilot study. SUBJECTS AND METHODS: Eligibility criteria
      were established to include patients with stage IIIc ovarian cancer in whom
      pleural effusions were not detected preoperationally, but prominent diaphragmatic
      metastases were observed when the abdomen was opened and those who submitted
      consent. Transdiaphragmatic thoracoscopy was performed after diaphragm stripping.
      Then, biopsy of the lesion suspected to be disseminated or the plural membrane of
      the thoracic opening was performed followed by washing cytology using
      physiological saline. RESULTS: Ten subjects were enrolled. Disseminated lesions
      were observed on plural membranes, and positive results were obtained in biopsy
      and washing cytology in 3 subjects. In addition, positive results were seen with
      biopsy alone in 2 subjects and with washing cytology alone in 2 subjects. Hence,
      a total of 7 subjects (70.0%) were up-staged to the level of stage IV.
      Postoperational complications were not observed in any of these cases.
      CONCLUSIONS: It was suggested that stage IIIc ovarian cancer with prominent
      diaphragmatic metastasis may advance to the level of stage IV from a clinical
      point of view even if carcinomatous pleural effusions are not detected pre
      operationally. Therefore, it is thought that this operational method is useful in
      the management of progressive ovarian cancer.

PMID- 19396012
TI  - Surgical management of the subdiaphragmatic mass: a sequential combined approach
      with laparoscopy followed by posterior thoracotomy.
AB  - Recurrent ovarian cancer in the upper abdomen involving the liver parenchyma and
      diaphragmatic muscle traditionally requires a major abdominal surgical procedure;
      this involves pubis to xyphoid incision and complete mobilization of the liver.
      We present a strategy for evaluating 4 cases with apparently isolated recurrence
      to the diaphragm and liver approached by a sequential 2-phase procedure,
      involving diagnostic laparoscopy and subsequent posterior lateral thoracotomy.
      Preliminary diagnostic laparoscopy was performed to distinguish candidates for
      either definitive laparoscopic treatment or posterior thoracotomy. Two patients
      with disease confined to the diaphragm were successfully treated by laparoscopy
      alone, whereas full-thickness diaphragmatic resection and liver metastasis
      excision with cavitational ultrasonic surgical aspirator was performed in the
      other 2 patients. Argon beam coagulation was used to control local hemostasis and
      to fulgurate any possible residual tumor at the margin of resection. This is a
      multidisciplinary approach that is technically feasible and safe, requiring a
      short hospital stay.

PMID- 19396014
TI  - Bleomycin treatment of brain tumors: an evaluation.
AB  - Bleomycin has been used in the treatment of brain tumors for over 30 years.
      Currently, we are evaluating electrochemotherapy (the use of electric pulses to
      enhance uptake of bleomycin) for patients with secondary brain tumors. We,
      therefore, reviewed the literature with specific reference to the tolerability
      and toxicity of bleomycin. Using the keywords 'brain' and 'bleomycin', a database
      search without date restriction was performed and over 500 articles were found.
      Twenty-five articles were used for this study based on relevance determined by:
      (i) clinical studies, (ii) use of bleomycin, and (iii) direct injection into
      brain tissue or cysts. There were two main indications for the use of bleomycin
      directly into the brain: (i) cystic tumors in the form of craniopharyngiomas and
      (ii) solid brain tumors such as glioblastomas and astrocytomas. The most frequent
      adverse effects reported were transient fever, headaches, nausea and vomiting,
      lethargy, and peritumoral edema. Out of 189 patients treated from 1973 to 2007,
      only five patients (3%) had severe and six patients (3%) had moderate adverse
      effects. One death was directly related to this treatment, where very high doses
      were used. Two patients developed loss of vision and two patients had hearing
      loss because of the treatment. All cases with severe and moderate adverse effects
      except one were patients with craniopharyngiomas and probably because of tumor
      localization in the deep brain. In conclusion, bleomycin injection into the brain
      has been fairly well tolerated at doses much higher than that used in
      electrochemotherapy.

PMID- 19396015
TI  - Association of a single nucleotide polymorphic variation in the human chromosome
      19q13.3 with drug responses in the NCI60 cell lines.
AB  - We studied the importance of certain polymorphisms on human chromosome 19q13.3
      for drug sensitivity in human tumor cell cultures. NCI60 is a panel of 60
      established tumor-derived cell lines, which have been tested for their
      sensitivity to tens of thousands of different drugs. Here we investigate the
      correlations between the responses of the NCI60 cells to different anticancer
      drugs and their respective alleles of five DNA polymorphisms located in a cancer
      related chromosomal area. One polymorphism, located in the 5' noncoding region of
      the gene ASE-1, alias CD3EAP, proved to be associated with drug sensitivity (P =
      0.025). The same polymorphism has previously been associated with treatment
      response of multiple myeloma after bone marrow ablation. The polymorphism ASE-1
      e1 was of importance for the drug response in the human cancer cell lines
      investigated and could eventually become important for individualized drug
      treatment in humans.

PMID- 19396016
TI  - A phase II trial of the Src-kinase inhibitor AZD0530 in patients with advanced
      castration-resistant prostate cancer: a California Cancer Consortium study.
AB  - Prostate cancer cells undergo neuroendocrine differentiation during androgen
      deprivation and secrete neuropeptides, hence activating androgen receptor
      regulated genes. Src-family protein kinases are involved in neuropeptide-induced
      prostate cancer growth and migration. A phase II trial of AZD0530, an oral Src
      family kinase inhibitor, in patients with advanced castration resistant prostate
      cancer was conducted. The primary endpoint was prostate cancer-specific antigen
      (PSA) response rate, defined as a 30% or greater decrease. A two-stage Simon
      design was used. Eligibility criteria included documentation of castration
      resistance (including antiandrogen withdrawal), adequate end-organ function, and
      performance status, and not more than one prior taxane-based chemotherapy
      regimen. AZD0530 was given at 175 mg orally once daily continuously. Rapid
      accrual led to 28 patients registering in the first stage. Median age was 67
      years. Sixteen patients had performance status (PS) 0, eight patients had PS 1,
      and four patients had PS 2. Nine patients (32%) had prior docetaxel-based
      chemotherapy. Five patients had transient PSA reductions not meeting PSA response
      criteria. Median progression-free survival time was 8 weeks. Treatment was
      generally well tolerated. AZD0530, a potent oral Src kinase inhibitor, is
      feasible and tolerable in this pretreated patient population but possessed little
      clinical efficacy as monotherapy. Strong preclinical evidence warrants further
      investigation of AZD0530 in earlier-stage prostate cancer or as combination
      therapy.

PMID- 19396018
TI  - Phase II study of capecitabine plus cisplatin in patients with gastric cancer.
AB  - A phase II study was conducted to assess the efficacy and toxicity of combination
      therapy with capecitabine and cisplatin in patients with de-novo advanced gastric
      cancer, and in patients with refractory/recurrent gastric cancer after previous
      nonplatinum-based therapy. Sixty-four patients were enrolled in the study. Of
      these, 50 patients had untreated gastric cancer, and 14 had received previous
      therapy with nonplatinum-based therapy. All patients received oral capecitabine
      1250 mg/m2 twice daily, days 1-14, and intravenous cisplatin 60 mg/m2 on day 1.
      This cycle was repeated every 3 weeks. Among the 50 previously untreated
      patients, three achieved complete response, and 19 had partial response, giving a
      response rate of 44% in the intention-to-treat population. The median time to
      progression and median overall survival were 6 months [95% confidence interval
      (CI): 1.4-10.6] and 9 months (95% CI: 5.7-12.3), respectively. In patients who
      had received previous therapy, clinical usefulness was evaluated resulting in
      response rate of 14%, disease control rate of 28.5%, and median overall survival
      of 4 months (95% CI: 3.1-4.9). The principal grade 3/4 adverse events were
      neutropenia (20%), anemia (14%). No neutropenic fever or treatment-related
      deaths. Capecitabine in combination with cisplatin is effective and well
      tolerated as first-line treatment in patients with advanced gastric cancer.
      Unfortunately, we could not positively suggest the usefulness of the same
      combination regimen as salvage therapy in patients with progressive or recurrent
      disease after nonplatinum-based therapy.

PMID- 19396017
TI  - A phase II study of carboplatin and paclitaxel for recurrent or metastatic head
      and neck cancer.
AB  - The aim of this study was to investigate the activity and safety of a regimen
      containing carboplatin and paclitaxel in patients affected by recurrent or
      metastatic head and neck cancer. Eligible patients were treated with a 3-week
      combination of paclitaxel 175 mg/m2 and carboplatin area under the concentration
      time curve 5 mg/ml/min for a maximum of four cycles. A total of 27 patients
      entered the study. One patient (3.7%) had a complete response, whereas six
      patients (22.2%) obtained a partial response. Stable disease was observed in
      seven patients (25.9%). The disease control rate was 51.8% (95% confidence
      interval: 32.0-71.3), whereas overall response rate was 25.9% (95% confidence
      interval: 11.1-46.3). The median overall survival was 8.0 months (range: 2-27),
      with a 1-year survival of 30.5%. The median progression-free survival was 1.0
      month (range: 0-14). Treatment-related deaths or episodes of neutropenic fever
      were not registered. Grades 3-4 neutropenia was observed in two patients (7.4%),
      grades 3-4 anaemia and thrombocytopenia in four (14.8%) and one (3.7%) patients,
      respectively. Nine patients (33.3%) experienced grades 1-2 and one patient (3.7%)
      grade 3 peripheral neuropathy. The combination of carboplatin and paclitaxel is
      safe and moderately effective for the treatment of recurrent or metastatic head
      and neck cancer.

PMID- 19396019
TI  - GSTP1 determines cis-platinum cytotoxicity in gastric adenocarcinoma MGC803
      cells: regulation by promoter methylation and extracellular regulated kinase
      signaling.
AB  - Detoxification mechanisms can play a pivotal role in determining tumor cell
      responses to platinum-based chemotherapy. Glutathione S-transferase-pi (GSTP1)
      belongs to a supergene family of detoxifying enzymes involved in the prevention
      of DNA damage and subsequent platinum resistance in numerous cancers. The role of
      GSTP1 in gastric cancer sensitivity to chemotherapy is, however, not known. In
      this study, we found that the human gastric cancer cell line MGC803 was
      significantly more sensitive to cis-platinum (CDDP) than the other gastric cancer
      lines examined (BGC823 and SGC7901). To explore the potential role of GSTP1 in
      drug resistance, we measured GSTP1 expression in these cells. GSTP1 mRNA and
      protein were not detectable in MGC803 cells; both were present in BGC823 and
      SGC7901 cells. GSTP1 CpG island DNA methylation was examined. We report that
      promoter hypermethylation was associated with the absence of GSTP1 expression in
      MGC803 cells. Treatment of these cells with 5-aza-2'-deoxycytidine, a DNA
      methyltransferase inhibitor, restored GSTP1 expression and suppressed sensitivity
      to CDDP. The selective mitogen-activated protein kinase/extracellular regulated
      kinase (ERK) pathway inhibitor PD98059 decreased GSTP1 expression in 5-aza-2'
      deoxycytidine-treated cells. A similar decrease was observed in the BGC823 and
      SGC7901 cell lines, suggesting that mitogen-activated protein kinase/ERK
      signaling stimulates GSTP1 expression. CDDP sensitivity was also enhanced by
      PD98059. These observations indicate that somatic promoter hypermethylation and
      impaired ERK signaling are associated with decreased GSTP1 expression and CDDP
      sensitivity in gastric cancer cell lines. Evaluation of promoter methylation and
      ERK activity may be useful for predicting tumor sensitivity to platinum-based
      chemotherapeutics.

PMID- 19396020
TI  - Spectroscopic investigations of the binding interaction of a new indanedione
      derivative with human and bovine serum albumins.
AB  - Binding of a newly synthesized indanedione derivative, 2-(2-hydroxy-3
      ethoxybenzylidene)-1,3-indanedione (HEBID), to human and bovine serum albumins
      (HSA and BSA), under simulated physiological conditions was monitored by
      fluorescence spectroscopy. The binding parameters (binding constants and number
      of binding sites) and quenching constants were determined according to literature
      models. The quenching mechanism was assigned to a Forster non-radiative energy
      transfer due to the HEBID-SA complex formation. A slightly increased affinity of
      HEBID for HSA was found, while the number of binding sites is approximately one
      for both albumins. The molecular distance between donor (albumin) and acceptor
      (HEBID) and the energy transfer efficiency were estimated, in the view of
      Forster's theory. The effect of HEBID on the protein conformation was
      investigated using circular dichroism and synchronous fluorescence
      spectroscopies. The results revealed partial unfolding in the albumins upon
      interaction, as well as changes in the local polarity around the tryptophan
      residues.

PMID- 19396021
TI  - Protective effects of celery juice in treatments with Doxorubicin.
AB  - The aim of this work was to investigate possible protective effect of celery
      juice in doxorubicin treatment. The following biochemical parameters were
      determined: content of reduced glutathione, activities of catalase, xanthine
      oxidase, glutathione peroxidase, peroxidase, and lipid peroxidation intensity in
      liver homogenate and blood hemolysate. We examined influence of diluted pure
      celery leaves and roots juices and their combinations with doxorubicine on
      analyzed biochemical parameters. Celery roots and leaves juices influenced the
      examined biochemical parameters and showed protective effects when applied with
      doxorubicine.

PMID- 19396023
TI  - For debate: childhood obesity - is there hope for therapy and prevention?
AB  - The diagnosis and treatment of co-morbidities of obesity that were once the
      province of clinicians who treated adult patients, are now among the daily
      activities of pediatricians. The approach to therapy usually involves changes in
      diet and activity, or medical or surgical therapies. However, limited proven
      effect of most efforts at treatment and limited personnel to handle the
      overwhelming needs make it clear that overweight and obesity in youth must be
      addressed by significant public health measures rather than primarily by a
      medical model of disease. This editorial argues that given the limited proven
      long-term efficacy of most treatment programs once obesity develops, the
      prevention of obesity should be at the forefront of our efforts to address this
      epidemic of chronic disease.

PMID- 19396022
TI  - Comparision of the cytotoxic effects of birch bark extract, betulin and betulinic
      acid towards human gastric carcinoma and pancreatic carcinoma drug-sensitive and
      drug-resistant cell lines.
AB  - Betulin and betulinic acid are naturally occurring pentacyclic triterpenes
      showing cytotoxicity towards a number of cancer cell lines. These compounds can
      be found in the bark of the many plants. In this report we have compared the
      cytotoxic activity of crude birch bark extract and purified betulin and betulinic
      acid towards human gastric carcinoma (EPG85-257) and human pancreatic carcinoma
      (EPP85-181) drug-sensitive and drug-resistant (daunorubicin and mitoxantrone)
      cell lines. Our results show significant differences in sensitivity between cell
      lines depending on the compound used, and suggest that both betulin and betulinic
      acid can be considered as a promising leads in the treatment of cancer.

PMID- 19396024
TI  - Overgrowth syndromes:from classical to new.
AB  - Overgrowth syndromes are a group of growth disorders which have gained joint
      attention from the fields of pediatrics, endocrinology and genetics. Major
      progress such as the identification of genetic causes has recently enhanced the
      delineation of the characteristic and non-characteristic manifestations,
      phenotype-genotype correlations and knowledge of the underlying
      pathophysiological mechanisms. As a consequence, the possibilities for
      distinction between the different overgrowth disorders have increased. Patients
      with either typical or non-typical features in whom no molecular abnormalities
      are found, form a basis for further research. Identification of new pathogenic
      alterations in these patients, best exemplified by the Marfan-related syndromes,
      has provided further understanding of the regulatory gene network involved. In
      light of recent developments and as an aid to the diagnostic process, the aim of
      this review is to give a comprehensive overview of the clinical, molecular
      genetic and pathophysiological aspects of each of the classic and new overgrowth
      syndromes.

PMID- 19396025
TI  - The genetics of idiopathic hypogonadotropic hypogonadism:unraveling the biology
      of human sexual development.
AB  - Idiopathic Hypogonadotropic Hypogonadism (IHH), a syndrome of GnRH deficiency, is
      characterized by varying degrees of sexual development disruption. When
      associated with anosmia, it is termed Kallmann Syndrome (KS). Although it was
      identified as a hereditary disorder over half a century ago, only during the last
      two decades have specific putative IHH genes been revealed, including: KAL1,
      GnRHR, FGFR1, GPR54, PROK2, PROKR2, FGF8, CHD7, TAC3 and TAC3R. Human mutations
      have shed light on the molecular control of GnRH neuronal embryogenesis and have
      elucidated elements critical in sexual development. Furthermore, the newly
      proposed oligogenic model has challenged the dogma of IHH being a single gene
      disorder and has heightened appreciation for the functional overlap of distinct
      signaling systems. This review offers an historical perspective to gene
      discoveries in IHH, genotype-phenotype correlations, and finally, discussion of
      the evolving complexity of the new IHH genetic model, no longer simply
      characterized by Mendelian inheritance.

PMID- 19396026
TI  - Breakthroughs in monogenic diabetes genetics: from pediatric forms to young
      adulthood diabetes.
AB  - Several monogenic forms of pancreatic beta-cell dysfunction leading to non
      autoimmune diabetes have been diagnosed early in life, in neonates or during
      infancy, in childhood or even in young adulthood, with genetically heterogeneous
      aetiologies.They include neonatal diabetes mellitus, non auto-immune diabetes in
      infancy and childhood, dominantly inherited young-onset diabetes and very rare
      diabetes-associated syndromes. More than ten genes that are highly expressed in
      the pancreatic beta-cell have been identified in these monogenic subtypes of
      diabetes, and several aetiological mechanisms of beta-cell dysfunction are
      involved including reduced beta-cell number, failure of glucose sensing and
      increased destruction of the beta-cell, which result in inadequate insulin
      secretion despite a chronic hyperglycemia. There is rising evidence that common
      polymorphisms in the genes implicated in monogenic diabetes may also be involved
      in susceptibility to adulthood type 2 diabetes. This review describes the major
      advances arising from the identification of the genetic and molecular mechanisms
      underlying the clinical features of various conditions of diabetes in the young,
      and how these new genetic and biological insights led to novel pharmacogenomic
      approaches.

PMID- 19396027
TI  - Genetic and molecular aspects of acromelic dysplasia.
AB  - The acromelic dysplasia group includes three rare disorders: Weill-Marchesani
      syndrome (WMS), Geleophysic dysplasia (GD) and Acromicric dysplasia (AD) all
      characterized by short stature, short hands and stiff joints. The clinical
      overlap between the three disorders is striking. Indeed, in addition to the
      diagnostic criteria, they all share common features including delayed bone age,
      cone shaped epiphyses, thick skin and heart disease. In contrast, a
      microspherophakic lens seems to be a characteristic feature of WMS whereas
      hepatomegaly and a severe outcome are encountered only in the most severe forms
      of GD. Finally, WMS is transmitted either by an autosomal dominant or an
      autosomal recessive (AR) mode of inheritance, GD by an autosomal recessive mode
      of inheritance and AD by an autosomal dominant mode of inheritance. Using genetic
      approaches, we have identified the molecular basis of WMS and GD which both
      involved the same superfamily of proteins, the ADAMTS [A Disintegrin-like And
      Metalloproteinase domain (reprolysin type) with ThromboSpondin type 1 repeats
      (TSR)]. We have found ADAMTS10 mutations in the recessive form of WMS and
      Fibrillin 1 mutations in the dominant form of WMS. More recently, we have
      identified ADAMTSL2 mutations in GD. The function of ADAMTS1 0 and AD AMTSL 2 are
      unknown. But the findings of FBN1 and ADAMTS10 mutations in WMS suggest a direct
      link between the two proteins. Using a yeast double hybrid screen, we have
      identified LTBP1 (Latent TGFbeta Binding protein 1) as a partner of ADAMTSL2. The
      combination of these findings suggests that ADAMTS10 and ADAMTSL2 are both
      involved in the microfibrillar network.

PMID- 19396028
TI  - Surgical versus non-surgical treatment of congenital hyperinsulinism.
AB  - Congenital hyperinsulinism is a functional disorder of insulin secretion. In its
      diffuse severe form, it is traditionally treated with over 95% pancreatectomy.
      However, even after this procedure normoglycemia is not always achieved. Non
      surgical therapy with frequent or continuous feeding, medication and close
      monitoring is another alternative. In this review we compare the two approaches
      to this condition focusing on early complications, diabetes, neurological outcome
      and home management issues. Early complications of pancreatectomy include
      mechanical, metabolic and infectious complications. Non-surgical interventions
      can be complicated by unwarranted effects of medications and of invasive
      procedures. Diabetes occurs with both approaches but much less frequently and
      years later with non-surgical treatment. Regarding neurodevelopmental outcome,
      most data come from heterogeneous groups. Nevertheless, it appears that outcome
      is not adversely affected by avoiding surgery. Home management is far more
      difficult for the non-surgical form. When the non-surgical approach is successful
      in achieving normoglycemia and parents are highly motivated, this mode of therapy
      should be considered.

PMID- 19396029
TI  - The association between phenotype and size of breast tumors induced by 1-methyl-1
      nitrosourea (MNU) injection in rats.
AB  - BACKGROUND: Administration of 1-methyl-1-nitrosourea (MNU) is considered a simple
      and rapid method for inducing breast tumors in rats. While most studies focus on
      the time frame of tumor development, there are little data on the development of
      breast tumor in relation to tumor size. Thus the current study was carried out to
      analyze the phenotype of MNU-induced tumors in relation to tumor size.
      MATERIAL/METHODS: Twenty-one 21-day-old female Sprague Dawley rats were
      administered intraperitoneally with MNU at a dose of 70 mg/kg body weight. The
      entire palpable tumor was excised when the tumor size reached the diameters of
      4.0+/-0.5 mm, 8.0+/-0.5 mm, 12.0+/-0.5 mm, and 16.0+/-0.5 mm and then subjected
      to histopathological assessment. RESULTS: Epithelial inclusion cysts and mammary
      adenomas made up most of the benign tumors, with four cases occurring together
      with malignant lesions. Ductal carcinoma in situ was seen in tumor sizes of 4.0+/
      0.5 mm or less. Among the malignant tumors, the cribriform type was seen
      predominantly at tumor sizes of less than 12.0+/-0.5 mm, while those with sizes
      of 12.0+/-0.5 mm or greater were of papillary type. Infiltrating ductal carcinoma
      no special type (IDC-NST) commonly seen in humans was also observed at tumor
      sizes greater than 12.0+/-0.5 mm. CONCLUSIONS: The tumors were found to be mainly
      of malignant type and the histological features of the induced tumors underwent
      changes as the tumor grew in size.

PMID- 19396030
TI  - Mechanical stretch induces pentraxin 3 release by alveolar epithelial cells in
      vitro.
AB  - BACKGROUND: Inflammation and pulmonary injury caused by mechanical ventilation is
      a complex process in which long pentraxin 3 (PTX3) is suggested to play an
      important role. The effect of mechanical stretch on PTX3 mRNA and protein
      expression in human alveolar epithelial cells (A549) was investigated.
      MATERIAL/METHODS: Immortalized A549 cells were exposed to tightly controlled and
      physiologically relevant cyclic mechanical stretch. A549 cells grown on collagen
      I BioFlex plates were exposed to square cyclic stretch at 0.3 Hz using the
      Flexercell system with 6% or 20% elongation of cells. In another group, cells
      were pretreated with small interfering RNA directed against PTX3 before stretch.
      After stretching, conditioned media and cells were collected and analyzed by
      Western blotting. Real-time PCR of cDNA generated from the stretched cells was
      performed. Apoptosis and viability of the cells following treatment were assessed
      using standard procedures. RESULTS: Mechanical cyclic stretch of 20% elongation
      led to increased PTX3 gene expression, increased release of PTX3 protein, and
      induced apoptosis and necrosis in A549 cells. Expression of PTX3 highly
      correlated with the severity of apoptosis. However, the results suggest that PTX3
      expression was significantly reduced by pretreatment of the A549 cells with small
      interfering RNA of PTX3. CONCLUSIONS: PTX3 may be an important mediator of lung
      tissue damage associated with mechanical stretch. Determining the production and
      regulation of PTX3 during mechanical ventilation may be critical in preventing or
      reducing ventilator-induced lung injury.

PMID- 19396031
TI  - Prevention of myocardial dysfunction by Eplerenon in experimental
      tachycardiomyopathy.
AB  - BACKGROUND: High-rate short-duration ventricular pacing induces myocardial
      hypokinesis that persists once the hemodynamic conditions have been recovered.
      The aim was to study the factors that determine the persistence of myocardial
      dysfunction when ventricular tachycardia has ceased and hemodynamic conditions
      have been restored. MATERIAL/METHODS: An in vivo experimental pig model was used
      consisting of a ventricular pacing series (n=10), a ventricular pacing and
      aldosterone blockade (eplerenon) series (n=6), and a control series without
      ventricular pacing (n=6). Electrical stimulation was performed from the
      epicardial base of the left ventricle at a frequency 60% above the basal rate for
      2 hours followed by a recovery period of 60 minutes. Cardiac and myocardial
      function parameters were studied. Plasma levels of aldosterone, renin activity,
      and glutathione were measured. RESULTS: Electrically induced tachycardia produced
      hemodynamic and myocardial changes that persisted after stimulation had ceased,
      accompanied by an increase in aldosterone and a coronary flow decrease. These
      changes were not seen when aldosterone activity was blocked by eplerenon. There
      was a non-significant elevation in glutathione levels. CONCLUSIONS: These data
      show that although participation of other neurohormones cannot be ruled out,
      aldosterone blockade (eplerenon) ameliorates myocardial dysfunction persisting
      after ventricular tachycardia by preventing coronary endothelial dysfunction.

PMID- 19396032
TI  - Peroxisome proliferator-activated receptor-gamma and retinoid X receptor-alpha
      expression in pancreatic ductal adenocarcinoma: association with
      clinicopathological parameters, tumor proliferative capacity, and patients'
      survival.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a
      ligand-activated transcription factor that forms heterodimers with the retinoid X
      receptors (RXRs), is overexpressed in various tumors, regulating many aspects of
      cancer biology. The aim of the present study was to evaluate the clinical
      significance of PPAR-gamma and RXR-alpha expression in pancreatic adenocarcinoma.
      MATERIAL/METHODS: PPAR-gamma and RXR-alpha protein expression was assessed
      immunohistochemically in tumoral samples of 65 pancreatic adenocarcinoma patients
      and statistically analyzed in relation to clinicopathological characteristics,
      tumor proliferative capacity, and patients' survival. RESULTS: Of the 65
      adenocarcinoma patients, 49 (75%) tested positive for PPAR-gamma and 55 (85%)
      stained positive for RXR-alpha. RXR-alpha positivity was significantly associated
      with tumor proliferative capacity and PPAR-gamma positivity (p=0.022 and p=0.043,
      respectively). PPAR-gamma and RXR-alpha staining intensity were associated with
      the histopathological tumor grade (p=0.003 and p=0.038, respectively).
      Significant associations of PPAR-gamma staining intensity and RXR-alpha
      expression with tumor size were also noted (p=0.041 and p=0.038, respectively).
      Moderate and intense PPAR-gamma staining intensity was associated with shorter
      overall survival in univariate analysis (log-rank test, p=0.023) and proved to be
      an independent prognostic factor in multivariate analysis (p=0.045), whereas RXR
      alpha failed to predict patients' survival. CONCLUSIONS: These data revealed that
      both PPAR-gamma and RXR-alpha were associated with pancreatic cancer
      characteristics. PPAR-gamma, but not RXR-alpha, was found to be an independent
      prognostic indicator. However, further molecular and clinical studies are
      required to delineate the potential clinical application of PPAR-gamma and RXR
      alpha in the prognosis and management of pancreatic adenocarcinoma patients.

PMID- 19396033
TI  - Fibrillin 1 gene with R2726W mutation is absent in patients with primary
      protrusio acetabuli and developmental dysplasia of the hip.
AB  - BACKGROUND: The morphological abnormality of the acetabulum in patients with
      primary protrusio acetabuli is almost the exact opposite as in those with
      developmental dysplasia of the hip. In primary protrusio acetabuli, the
      acetabulum is excessively deep, while in developmental dysplasia of the hip, the
      acetabulum is excessively shallow. A genetic etiology has been proposed in
      developmental dysplasia of the hip, while the etiology of primary protrusio
      acetabuli is widely debated. Primary protrusio acetabuli may represent a hitherto
      unidentified metabolic defect, and a possible candidate for such genetic
      influence is the R2726W variant of the fibrillin 1 (FBN1) gene, which segregates
      with isolated skeletal features of individuals with Marfan syndrome.
      MATERIAL/METHODS: We identified 26 patients with primary protrusio acetabuli and
      45 patients with developmental dysplasia of the hip through clinical and
      radiographic examinations. We included 95 normal controls in the study. DNA from
      peripheral blood was used in genotyping for the FBN1 R2726W mutation using
      pyrosequencing. RESULTS: No mutant alleles were identified in any patients or
      controls. CONCLUSIONS: The R2726W mutation is not responsible for skeletal
      malformation of primary protrusio acetabuli in our population, although there may
      be unidentified genetic variants in either FBN1 or other genes that control
      acetabular morphology.

PMID- 19396034
TI  - Keratin 7 expression as an early marker of reflux-related columnar mucosa without
      intestinal metaplasia in the esophagus.
AB  - BACKGROUND: The role of Barrett esophagus in carcinogenesis is widely accepted,
      but the significance of esophageal columnar mucosa without histological
      intestinal metaplasia, known as columnar-lined esophagus, is debated.
      MATERIAL/METHODS: We studied 128 patients free of Helicobacter pylori with reflux
      related symptoms and columnar mucosa in the esophagus at endoscopy, 106 patients
      with Barrett esophagus (referred to as the Barrett group) and 22 patients without
      intestinal metaplasia (columnar group). Samples from 20 subjects free of H.
      pylori were used as controls. Immunostaining for keratin 7 (KRT7), keratin 20
      (KRT20), caudal type homeobox 2 (CDX2), mucin 2, oligomeric mucus/gel-forming
      (MUC2), and tumor protein p53 (TP53) was assessed. RESULTS: Samples taken 1 cm
      above the gastroesophageal junction showed KRT7 staining in all cases in the
      Barrett and columnar groups and none in the control group. Immunostaining for
      TP53 was absent in the control group, and more frequent in the columnar group (7,
      31.8%) compared with the Barrett group (14, 13.2%, P=0.033). In the columnar
      group, low grade dysplasia and TP53 expression was seen in 7 of 22 biopsy
      specimens (31.8%) at baseline and in 4 additional specimens after 2 years, for a
      total of 11 specimens (50.0%). CONCLUSIONS: The expression of KRT7 might help to
      explain the pathological, reflux-related nature of columnar-lined esophagus, as
      aberrant expression in a very early stage of the multistep Barrett esophagus
      progression. Expression of KRT7 may occur in basal glandular cells as a result of
      their multipotentiality and susceptibility to immunophenotype changes induced by
      reflux.

PMID- 19396035
TI  - Endogenous steroid sex hormones and atherosclerosis of retinal arteries in men.
AB  - BACKGROUND: Increasing evidence suggests that both male and female sex hormones
      may be associated with the development of atherosclerosis, but almost all such
      data are based on studies of patients with coronary artery disease. To our
      knowledge, there are no data on the effects of endogenous sex hormones on
      atherosclerosis of the retinal arteries in men, and the purpose of this study was
      to explore that association. MATERIAL/METHODS: In 101 consecutive adult male
      patients treated in a university hospital outpatient clinic, atherosclerotic
      changes of the retinal vessels were identified prospectively by direct
      ophthalmoscopy and were graded on a scale of 1 to 4 according to Scheie.
      Commercial radioimmunoassay kits were used to measure serum levels of
      testosterone, estradiol, progesterone, androstenedione, and
      dehydroepiandrosterone sulfate. The chi-square test was used to compare the
      results with those from 47 matched male subjects with healthy retinal vessels.
      RESULTS: Retinal vessel atherosclerosis was inversely correlated with the serum
      progesterone concentration (P<0.001). The lower the progesterone concentration,
      the more advanced the stage of retinal vessel disease. A similar but less
      statistically significant correlation was noticed for dehydroepiandrosterone
      sulfate (P<0.05). A weak (P<0.05) similar association between the degree of
      retinal artery atherosclerosis and estradiol levels was also found. CONCLUSIONS:
      Low endogenous progesterone levels and, to a degree, low dehydroepiandrosterone
      sulfate and estradiol levels might be associated with atherosclerosis of the
      retinal arteries in men.

PMID- 19396036
TI  - Screening for B- and T-cell defects in Egyptian infants and children with
      suspected primary immunodeficiency.
AB  - BACKGROUND: Primary immunodeficiency diseases are underdiagnosed in developing
      countries. The aim of this study was to identify primary B- and T-cell immune
      defects in Egyptian infants and children with clinical criteria indicating
      primary immunodeficiency disease. MATERIAL/METHODS: We enrolled 100 consecutive
      infants and children clinically suspected to have primary immunodeficiency
      disease. Subjects were evaluated with respect to immunodeficiency-related score,
      complete blood count, erythrocyte sedimentation rate, serum immunoglobulin (Ig) A
      and tetanus IgG antibody estimation, and Candida and tuberculin intradermal
      testing. Subjects showing IgA deficiency underwent serum total IgG, IgM, and IgE
      measurement, and lymphopenic patients underwent lymphocyte subset counting by
      flow cytometry. RESULTS: Thirty-five subjects showed laboratory evidence of T-
      and/or B-cell immunodeficiency and showed significantly higher immunodeficiency
      related scores, a greater frequency of hospitalization, and were more likely to
      have no bacillus Calmette-Guerin scar and a negative Candida skin test.
      Laboratory evaluation revealed evidence of predominant B-cell defects in 19
      subjects, T-cell defects in 8, and combined immunodeficiency in 8. An
      immunodeficiency-related score of > or =6 was associated with 71% of the immune
      defects, and a score > or =8 was predictive of significant immune derangement.
      The most helpful screening tests for B-cell defects were those for serum IgA and
      antitetanus IgG, whereas those for T-cell immunodeficiency were peripheral blood
      lymphocyte count and Candida sensitivity skin test. CONCLUSIONS: Our screening
      procedures allowed for identification of most of the subjects requiring further
      evaluation of primary immunodeficiency disease in this study. Widescale screening
      of neonates and older children for primary immunodeficiency disease is indicated.

PMID- 19396037
TI  - Effects of physiological parameters on intraoperative somatosensory-evoked
      potential monitoring: results of a multifactor analysis.
AB  - BACKGROUND: In scoliosis surgery, intraoperative somatosensory-evoked potentials
      (SEPs) are affected by physiological parameters, which also have a complicated
      interaction with each other. Previous studies have reported on how these
      parameters individually affect SEPs. However, there has been no systematic
      analysis of these effects. The purpose of this study was to investigate the
      relationships between variations in intraoperative SEPs and various physiological
      parameters. MATERIAL/METHODS: Seventy scoliosis patients who underwent
      intraoperative SEP monitoring were enrolled in this retrospective study.
      Variations in latency and amplitude were analyzed to evaluate their relationships
      to blood pressure, heart rate, temperature, and partial pressure of alveolar
      carbon dioxide (PaCO2) using gray correlation degree analysis. RESULTS:
      Variations in latency and amplitude correlated most closely with variations in
      temperature, PaCO2, and heart rate, followed by variations in diastolic and then
      systolic blood pressure. CONCLUSIONS: Variations in different physiological
      parameters are related to variations in intraoperative SEPs to different degrees.
      Monitoring specialists should take this into consideration when making decisions
      based on abnormal SEPs.

PMID- 19396038
TI  - Factors influencing the clinical course of popliteal artery aneurysm.
AB  - BACKGROUND: The literature concerning the threshold for intervention in
      asymptomatic popliteal aneurysm is inconsistent. The purpose of this study was to
      identify factors related to the clinical course of popliteal aneurysms.
      MATERIAL/METHODS: We analyzed the influence of patients' age and sex, diameter of
      the aneurysm, atherosclerotic risk factors, use of antiplatelet medications and
      statins, lipid profile, and the presence of other aneurysms on the symptoms and
      status of the popliteal aneurysm (patent or thrombosed). RESULTS: Of 86 cases of
      popliteal aneurysms in 61 patients, 18 were asymptomatic, 22 were associated with
      intermittent claudication, 26 with acute limb ischemia, 10 with critical limb
      ischemia, and 10 with nonischemic symptoms. There was a trend of borderline
      statistical significance for smaller diameter in asymptomatic popliteal
      aneurysms. It was not possible to discriminate between cases with and without
      limb-threatening symptoms, or patent versus thrombosed popliteal aneurysm based
      on the diameter of the aneurysm. The 58 cases with hypercholesterolemia less
      frequently presented with limb-threatening symptoms (32.8%) compared with the 28
      patients without hypercholesterolemia (60.7%, P=.02), and more often had patent
      aneurysms (55.2% versus 28.6%, P=.04). Patients with patent popliteal aneurysms
      were younger (P=.047) and were more frequently on statins (30% versus 12.5%,
      P=.063). CONCLUSIONS: Expectations regarding clinical course and indications for
      intervention in popliteal aneurysm should not be based on its diameter. Statins
      may have a beneficial influence on the clinical course of popliteal aneurysms,
      but further investigations are required.

PMID- 19396039
TI  - Life after coronary stent thrombosis.
AB  - BACKGROUND: Coronary stent thrombosis is a catastrophic complication of
      percutaneous coronary intervention. There is a paucity of long-term data
      regarding the clinical outcome of patients who have suffered stent thrombosis.
      MATERIAL/METHODS: We sought to assess the long-term clinical outcome of patients
      who suffered de novo ST-segment elevation myocardial infarction as well as those
      who suffered ST-segment elevation myocardial infarction as a result of stent
      thrombosis. In both patient groups, major cardiac adverse events were studied
      during a 1-year follow-up period. RESULTS: A total of 1890 consecutive patients
      who presented with ST-segment elevation myocardial infarction during the period
      January 2003 to December 2005 were studied: 1843 (97.5%) suffered de novo ST
      segment elevation myocardial infarction, and 47 (2.5%) suffered ST-segment
      elevation myocardial infarction as a consequence of stent thrombosis. The rate of
      cardiogenic shock was significantly higher in the stent thrombosis group than in
      the de novo thrombosis group (21.3% vs 4.8%, respectively) (P<0.001). Mortality
      rates at 30 days (6.4% vs 8.8%) and at 1 year (17.0% vs 14.9%) showed no
      significant difference between the 2 groups. The repeat revascularization rate
      was higher among patients with post-stent thrombosis (35.7% vs 9.1%) (P<0.001),
      as was the major cardiovascular event rate (57.1% vs 31.2%) (P<0.001).
      CONCLUSIONS: The long-term clinical outcome of patients who have suffered stent
      thrombosis is poor. Additional research is warranted to further improve
      therapeutic measures associated with stent thrombosis.

PMID- 19396040
TI  - Orderliness of cortisol, growth hormone, and leptin secretion in short-normal pre
      pubertal boys and girls.
AB  - BACKGROUND: The approximate entropy (ApEn) of the secretion of one hormone is a
      measure of its irregularity of secretion, while cross-approximate entropy (cross
      ApEn) assesses the interaction between the secretion of two hormones. The aim was
      to assess the regularity and interplay of the secretory profiles of leptin (Le),
      cortisol (F), and growth hormone (GH). MATERIAL/METHODS: Spontaneous 24-hour Le,
      F, and GH secretions were analyzed with ApEn and cross-ApEn in 11 short-normal
      pre-pubertal children (5 boys and 6 girls). RESULTS: Although the Le, F, and GH
      levels were not significantly different between the boys and girls, the boys
      showed more orderly F secretion than the girls, while the latter showed more
      orderly GH and Le secretions evaluated by ApEn. Moreover, the synchrony between
      the secretory profiles of Le and the other two hormones as evaluated by cross
      ApEn was significantly more regular in the boys. CONCLUSIONS: Differences in the
      orderliness of secretion of Le, F, and GH were shown between pre-pubertal boys
      and girls, while increased synchrony was seen between the secretions of Le and GH
      as well as Le and F in pre-pubertal boys compared with girls. These findings
      complement the authors' previous research using cross-correlational analyses
      which demonstrated that the secretory profiles of Le, F, and GH were correlated
      in time.

PMID- 19396041
TI  - Aggressive and impulsive behaviors in Frontotemporal dementia and Alzheimer's
      disease.
AB  - BACKGROUND: Differentiating FTD and AD is of great clinical significance, due to
      the very different efficacy of cholinesterase inhibitors in the two disorders.
      Previous studies have pointed to behavioral differences in FTD and AD, but less
      attention has been paid to comparing aggressive and impulsive behaviors in the AD
      and the FTD. MATERIAL/METHODS: Nursing home residents diagnosed with AD
      (NINCDS/ADRDA criteria) or the behavioral variant of FTD (Frontotemporal Dementia
      and Pick's Disease Working Group criteria) were included in the research group.
      Individuals diagnosed with AD who showed atrophy of the frontal lobes in
      neuroimaging were excluded from the study, as were patients matching the clinical
      criteria for bvFTD, but with lesions in the temporal lobes. Agitation and
      aggressive behaviors were assessed using the Cohen-Mansfield Agitation Inventory
      (CMAI), whereas behavioral and psychological symptoms were assessed with the
      Neuropsychiatric Inventory - Nursing Home Version (NPI-NH). RESULTS: The overall
      NPI-NH score, including with some partial scores (apathy/indifference and
      disinhibition), together with the intensity of aberrant motor behavior
      differentiated individuals with AD from those with bvFTD. On the CMAI scale, both
      the overall score and physical aggressive behaviors differentiated the two study
      groups. CONCLUSIONS: Our research confirms previous results indicating a greater
      intensity of behavioral pathology in FTD. A detailed assessment of aggressive
      behaviors revealed further differences between AD and FTD in this respect.

PMID- 19396042
TI  - Normative values for the 13C-mixed triglyceride breath test in two age groups.
AB  - BACKGROUND: To investigate if age affects the results of the 13C-mixed
      triglyceride (13C-MTG) breath test. MATERIAL/METHODS: Two groups of 12 healthy
      subjects (group Y, 25.0+/-0.7 years; group MA, 48.8+/-2.4 years), each comprising
      6 men and 6 women, were examined. The fasted volunteers had a 349-kcal test
      breakfast of 50 g of white bread with 30 g of butter to which 300 mg of 13C-MTG
      was added. Then a series of samples of exhaled air for the measurement of 13CO2
      concentration was collected over a period of 9 hours. RESULTS: A maximum
      momentary 13CO2 breath excretion of 9.6+/-0.5%dose/h at 295+/-19 min in the young
      subjects and of 9.4+/-0.4%dose/h at 270+/-15 min in the middle-aged volunteers
      was observed. The group curves of cumulative 13C recovery in breath air exhibited
      a virtually overlapping time course. The 6-h cumulative 13C recovery amounted to
      32.01+/-1.78%dose and 31.84+/-1.73%dose in the Y and MA groups, respectively.
      Extension of the collection of breath air samples from the standard six to nine
      hours resulted in an increase in the cumulative 13C recovery by 51.5+/-3.2%.
      Accordingly, the 9-h cumulative 13C recovery was 47.59+/-2.26%dose and 48.28+/
      2.36%dose in the Y and MA groups, respectively. CONCLUSIONS: An age difference of
      over two decades does not compromise intrajejunal lipolytic activity taken as a
      measure of pancreatic exocrine function. Therefore reference values for the 13C
      MTG breath test can be obtained from a population of healthy subjects of a
      relatively wide age range.

PMID- 19396043
TI  - Delirium and postoperative cognitive dysfunction after general anesthesia.
AB  - BACKGROUND: General anesthesia is characterized by unconsciousness, analgesia,
      muscle relaxation, and depression of reflexes, generally in response to the
      administration of chemical agents that induce reversible unconsciousness. Study
      of the cognitive neuroscientific basis of general anesthesia involves evaluation
      of the effect of anesthetic agents on consciousness and the brain mechanisms
      underlying cognitive function. Central nervous system dysfunction after
      anesthesia and/or surgery can occur at any age but is a particular issue for
      elderly patients. Studies of delirium and postoperative cognitive dysfunction
      have been published in many countries since the end of the last century. We
      present a discussion of delirium disorders and a review of the literature. CASE
      REPORT: We also present case reports for 2 patients who underwent general surgery
      for epilepsy. The first patient experienced postoperative visual illusions,
      hallucination, and time and space disorientation. The second patient experienced
      a postoperative zombie-like delirium state. The status of both patients was
      improved in response to treatment with methylprednisolone. The first patient also
      received amantadine sulfate, and the second patient received antiepileptic drugs.
      CONCLUSIONS: The brain is the main target organ for anesthetic and adjuvant
      drugs, and age-associated changes in the brain have important implications with
      respect to general anesthesia. Anesthetists and surgeons have suspected for many
      years that some patients suffer a postoperative decline in cognitive function.
      The condition generally has a good outcome because oxidative nerve cell
      derangements and neurotransmitter imbalances are transient.

PMID- 19396044
TI  - Ultrasound techniques to measure the optic nerve sheath: is a specialized probe
      necessary?
AB  - BACKGROUND: Ultrasound measurement of the optic nerve sheath diameter (ONSD) has
      been shown to correlate with intracranial pressure (ICP). This study looked at
      intra-observer and inter-observer reliability among three emergency physicians
      (EPs) using three different imaging protocols. MATERIAL/METHODS: Ocular
      ultrasound was performed in 20 healthy volunteers. Each physician obtained 3
      measurements of the right eye ONSD with both the 10-5 MHz and 13-6 MHz probes
      using the axial imaging technique (experiment 1). The ONSD was then measured with
      the 10-5 MHz probe using the axial technique and the intracavitary 8-5 MHz probe
      using the coronal technique (experiment 2). RESULTS: In experiment 1, larger
      measurements were obtained with the standard 10-5 MHz probe with an adjusted
      difference of 0.21 mm (p<0.001). The standard deviation between intra-observer
      measurements for the 10-5 MHz probe was slightly but not significantly larger
      with an adjusted difference of 0.039 (p=0.10). In experiment 2, larger
      measurements were obtained with the standard 10-5 MHz probe with an adjusted
      difference of 0.91 mm (p<0.001). The standard deviation between intra-observer
      measurements was greater for the 10-5 MHz probe with an adjusted difference of
      0.06 (p=0.03). The inter-observer measurements in experiment 2 had significantly
      larger variance with the 10-5 MHz probe (p=0.001). CONCLUSIONS: These data
      suggest comparable precision and inter-observer reliability can be achieved.
      However, larger values when using the 10-5 MHz probe suggest different cut-off
      thresholds for normal upper limits. The coronal imaging technique demonstrated
      less inter-rater variance and may be a better technique when such small
      measurement differences are important.

PMID- 19396045
TI  - Evidence for vestibular processing in the caudal fastigial nucleus using vector
      addition.
AB  - BACKGROUND: While strong vestibular input to the fastigial nucleus has been
      demonstrated, little is known on how this is integrated in the oculomotor region
      of the caudal area of fastigial nucleus. In this study, single units in the
      caudal region of the fastigial nucleus were recorded in the rat, while applying
      sinusoidal galvanic stimuli to the labyrinths. MATERIAL/METHODS: The left and
      right labyrinths were polarized with either monaural or binaural sinusoidal
      stimuli (0.5 hertz), with stimulus phase shifts between right and left in 90
      degrees steps (90 degrees, 180 degrees, 270 degrees, 360 degrees). The study
      describes the interaction and integration between the information of both
      labyrinths in the caudal fastigial nucleus. RESULTS: In 23 neurons, the
      relationship between input (galvanic stimuli to the labyrinths) and output
      (neuronal discharge) was analyzed for a series of stimuli (102 recordings in
      total). During monaural stimulation, phase shifts greater than 45 degrees were
      observed in 14 of 23 neurons (60.9%) during stimulation to the left and right
      labyrinths. To explain this phenomenon and the previously observed tuning
      characteristics in the fastigial nucleus, the neuronal responses were regarded as
      vectors. Thus, the observed response for binaural stimulation appeared to
      correspond to a vector addition of the left and right vestibular afferents. Of
      the 23 neurons, 14 neurons (60.9%) indicated a difference between predicted and
      measured values of less than 14.1 degrees. CONCLUSIONS: The findings support a
      working model based on vector addition of vestibular afferents in the caudal
      fastigial nucleus.

PMID- 19396046
TI  - Healthcare claims for identifying the level of diagnostic investigation and
      treatment of cancer.
AB  - BACKGROUND: Healthcare claims data were used to better understand the diagnostic
      investigation and treatment of cancer. MATERIAL/METHODS: A retrospective cohort
      study was used involving claims data from a large insurance company. Analyses
      were based on electronic claims data from 1997 through 2006 for enrollees aged 15
      64 years. RESULTS: This study showed that 96% of all first time cancer-related
      claims involved physician services. The percentage of physician services
      involving diagnostic workup in the form of some combination of blood testing,
      radiology, and surgery was 89% for non-skin cancer and 95% for skin cancer. The
      percentage of physician services involving some combination of chemotherapy,
      radiation, and surgery was 24% for non-skin cancer and 14% for skin cancer. Thus,
      for cancer (excluding skin cancer) the ratio of diagnostic workup to treatment
      was 2.7 to 1. For skin cancer, the ratio was 6.3 to 1. The percentage receiving
      treatment ranged from 13% for the male genital system to 46% for cancers of the
      bones and joints. Beyond cancers of the male or female genital systems, cancer
      related claims involving treatment were 34% (95% CI 17-54%) higher for females
      than males. CONCLUSIONS: Healthcare claims data can be used to generate useful
      information for physicians and their patients about the process and nature of the
      diagnostic workups and treatment that typically occur when cancer is suspected.

PMID- 19396047
TI  - Related factors to disparity of diabetes care in Iran.
AB  - BACKGROUND: We determined, in Iranian patients with diabetes mellitus, the
      prevalence of inadequate glycemic control and its predictors. MATERIAL/METHODS:
      The data from a national population-based survey that included a random sample of
      89 404 Iranian individuals in 2005 were analyzed. In that sample, 2923 diabetic
      subjects (age range, 25-64 years) were identified. We linked the results of their
      fasting plasma glucose levels with demographic and behavioral variables to
      determine predictors of poor glycemic control. RESULTS: About 57% of the subjects
      had a fasting plasma glucose level of > or =130 mg/dL. That percentage was
      comparable in male and female subjects and in literate and illiterate subjects.
      However, inhabitants in rural areas controlled their fasting plasma glucose level
      about 11% better than did subjects who lived in an urban area. We also found that
      control of the fasting plasma glucose level was much better in relatively younger
      diabetic patients. Diabetic subjects with a family history of type 2 diabetes
      mellitus exhibited a higher uncontrolled fasting plasma glucose level than those
      without positive family history of diabetes. CONCLUSIONS: The percentage of
      uncontrolled type 2 diabetes found in our study suggests that the Iranian
      healthcare system should devote more attention to that disorder, particularly in
      elderly individuals, who are more vulnerable to the complications of diabetes and
      control their disorder less well than do younger diabetic patients. The recent
      integration of diabetic care in primary healthcare systems in Iranian rural areas
      was found to have a promising effect on community health.

PMID- 19396048
TI  - Azathioprine therapy in steroid-dependent patients with Crohn disease: results of
      a 10-year longitudinal follow-up study.
AB  - BACKGROUND: Studies assessing the efficacy of azathioprine in steroid-dependent
      patients with Crohn's disease are scarce. The aim of this study was to assess the
      long-term efficacy and safety of azathioprine, and factors associated with
      sustained response, in steroid-dependent patients with Crohn's disease.
      MATERIAL/METHODS: In this prospective, observational study, adult steroid
      dependent subjects with Crohn's disease receiving azathioprine therapy were
      assessed over a 10-year period. Azathioprine dosage was adjusted according to
      clinical response and occurrence of adverse events. Median treatment duration was
      83 months. Steroid therapy was tapered according to protocol. RESULTS: A total of
      106 subjects were included. The proportion of subjects remaining in sustained
      steroid-free remission at 12, 24, 36, 48, and 60 months was 0.61, 0.73, 0.72,
      0.70, and 0.70, respectively. Thereafter, the rate of weaning from steroids
      decreased gradually, reaching a nadir of 0.41 at 108 months. Median time to
      complete steroid withdrawal was 6 months. Demographic, azathioprine dose, and
      disease-related data did not correlate with remission. By multivariate analysis,
      only decreased mean leukocyte count during follow-up was independently associated
      with steroid-free remission (P=.001). Subjects who achieved an annual mean
      leukocyte count <6,000/mm(3) were more likely to sustain steroid-free remission
      (P=.01). Serious adverse events in response to azathioprine were uncommon.
      CONCLUSIONS: Azathioprine therapy offers a meaningful option in the management of
      steroid-dependent Crohn's disease for up to 10 years. A persistent decrease in
      leukocyte count may provide a surrogate marker of sustained steroid-free
      response.

PMID- 19396049
TI  - Effects of fenofibrate treatment on prothrombotic state in patients with
      metabolic syndrome in relation to smoking and diabetes.
AB  - BACKGROUND: Patients with metabolic syndrome (MS) are characterized by enhanced
      procoagulant activity caused by an increased fibrinogen (Fb) level, impaired
      fibrinolysis, and platelet activation. Fibrate treatment usually normalizes these
      conditions. The aim was to determine the effect of fenofibrate treatment on Fb
      level, fibrinolysis, and platelet function in patients with MS with regard to
      smoking status and type 2 diabetes. MATERIAL/METHODS: Sixty-four patients with
      MS, including 20 active smokers, without clinical features of coronary heart
      disease were enrolled in the study. Before and during treatment with fenofibrate
      all patients took antihypertensive drugs and 25 patients with type 2 diabetes
      used oral antidiabetic drugs. Before and after the treatment the levels of
      lipids, fasting glucose insulin, Fb, PAI-1, t-PA, and platelet function expressed
      as closure time (CT, after Coll/Epi and Coll/ADP) were measured. RESULTS:
      Fenofibrate treatment resulted in normalization of abnormal lipid profiles and a
      reduction in Fb level. In smokers an increase in PAI-1 level and CT shortening
      after Coll/Epi and after Coll/ADP were found. In nonsmokers, CT was prolonged
      only after Coll/Epi. A slight reduction in PAI-1 and a reduction in fasting
      glucose were noted in the diabetics. CONCLUSIONS: Fenofibrate partially corrected
      procoagulant state in patients with MS, which was manifested by a significant
      reduction in Fb level in all patients and inhibition of platelet function
      exclusively in nonsmokers. Smoking neutralizes the effects of treatment with
      fenofibrate as absence of inhibition of platelet function and a lack of
      improvement of the fibrinolysis system were observed in them.

PMID- 19396050
TI  - Xenobiotic perturbation of endogenous morphine signaling: paradoxical opiate
      hyperalgesia.
AB  - The clinical literature has extensively documented diverse, potentially
      debilitating, side-effects of pharmaceutical dosages of morphine and morphine
      congeners administered for management of acute and chronic pain. Paradoxically,
      morphine is capable of engendering state-dependent hyperalgesic responses that
      appear to be functionally linked to secondary activation of N-methyl-D-aspartate
      (NMDA) receptors coupled to Ca++-evoked nitric oxide (NO) production. Similar
      biochemical events have been associated with the development of morphine
      tolerance. Recent lines of complementary evidence support both the existence and
      biological importance of cellular regulatory pathways mediated by endogenously
      synthesized, chemically authentic morphine. Cellular "morphinergic" signaling is
      mediated by cognate six-transmembrane helical domain (TMH) micro3 and micro4
      opiate receptors linked to activation of constitutive NO synthase (cNOS). Based
      on the compelling association of both endogenous and exogenous morphine
      activation with enhanced NO production, we advance a hypothesis that morphine
      administered as a pharmaceutical/xenobiotic agent adversely perturbs normative
      "morphinergic"/NO signaling within discrete cellular microdomains. Accordingly,
      pharmaceutical and/or physiological disruption of basic metabolic events
      regulated by "morphinergic"/NO signaling is proposed to account for state
      dependent morphine-mediated hyperalgesia, tolerance development, and related
      disruptive cellular adaptations.

PMID- 19396051
TI  - Cardiac magnetic resonance in acute myocarditis and dilated cardiomyopathy.
AB  - Cardiac magnetic resonance imaging can visualize ventricular size and function
      and moreover tissue composition. This allows for detection of myocardial edema
      and increased contrast uptake typical for inflammation. In a subset of
      myocarditis-patients typical irreversible fibrotic lesions can be detected. In
      clinical routine CMR can contribute to the differentiation of acute myocarditis
      and acute infarction or stress-induced cardiomyopathy. In various systemic
      diseases CMR can help to detect myocardial involvement. In dilated cardiomyopathy
      CMR enables precise quantification of ventricular size and function. The
      detection of myocardial fibrosis by CMR has prognostic implications.

PMID- 19396052
TI  - What have the 'omics done for endometriosis?
AB  - A review of the current literature was attempted in order to determine to what
      degree new technological features, such as the use of proteomics, genomics, and
      gene microarrays, have contributed to the elucidation of the specific pathways to
      the formation of endometriosis as well as to the discovery of potential
      biomarkers and new treatment strategies. Endometriosis is well described as a
      condition in which multiple genetic components and still foggy environmental risk
      factors are important determinants of the disease's origin, maintenance,
      persistence, and clinical outcome. The concept is that because of the special
      features and complexity of the disease, endometriosis is ideally suited as a
      target for genome- and proteome-wide scanning. Reviewing the current literature
      we found that, apart from the better understanding of the pathophysiology and the
      metabolic pathways which lead to potential biomarkers for endometriosis, there
      are still issues to be clarified and applications to be achieved. The evolving
      genomic and proteomic technologies remain poised to revolutionize the diagnosis
      and treatment of endometriosis but have not yet lead to a single new therapy or
      tested biomarker. The reasons have mainly to do with the complex and
      multifactorial character of the disease itself.

PMID- 19396053
TI  - No improvement in studies reporting the diagnostic accuracy of B-type natriuretic
      peptide.
AB  - BACKGROUND: B-type natriuretic peptides (BNP and NT-proBNP) appeared as important
      tools for diagnosis, risk stratification, and therapeutic decision making in
      cardiovascular diseases. The aim of the study was to assess fulfillment of the
      QUADAS and major STARD criteria in B-type natriuretic peptide diagnostic accuracy
      studies and describe the relationship between the year of study publication. the
      journal's impact factor, and the quality of diagnostic accuracy.
      MATERIAL/METHODS: In a cross-sectional study, electronic and manual searches of
      MEDLINE and EMBASE databases from January 2004 through April 2007 for diagnostic
      accuracy studies of BNP and NT-proBNP were performed. The quality of articles was
      assessed using of the 14-item QUADAS tool supplemented by a subjectively prepared
      list of 8 less reproducible STARD criteria (total of 22 possible points).
      RESULTS: Twenty-eight articles suitable for analysis were found. The median
      number of points was 15. Only 2 of the 28 articles satisfied all 22 criteria.
      Clinical data availability was the only item described sufficiently in all
      papers. A flow diagram was found in only one paper. There were no differences in
      article quality in relation to the year of publication and no association between
      article quality and the impact factor of the journal in which it was published.
      CONCLUSIONS: Imperfect quality of studies reporting the diagnostic accuracy of B
      type natriuretic peptides is related to neither the year of publication nor the
      journal's impact factor. The problem of reporting diagnostic accuracy cannot be
      neglected, especially when a new index test becomes common in clinical practice.

PMID- 19396054
TI  - Transesophageal echocardiography in the OR and ICU.
AB  - The application of transesophageal echocardiography (TEE) in the perioperative
      setting has been expanding over the past decades. TEE has become increasingly
      important in the management of critically ill patients both in the operating room
      and in the intensive care unit (ICU). TEE is a semi-invasive imaging technique
      that provides a rapid, real-time, bedside assessment of cardiac function and
      morphology. It provides information about the anatomy of all cardiac structures
      and their functional status. A comprehensive exam evaluates both ventricles'
      morphology, dimensions, and wall motion. It can also detect any anatomical
      abnormalities and the presence of intracardiac masses or thrombi. Over the last
      few years, a large number of studies in different ICU and critical care settings
      and populations have demonstrated the feasibility of TEE in the management of
      hemodynamic instability. Hemodynamic parameters, such as volumes and pressures,
      can be obtained via TEE assessment of cardiac performance and may be helpful for
      diagnosis and treatment. Intraoperative TEE is actually considered an important
      diagnostic tool in patients scheduled for cardiac surgery as well as in high-risk
      patients undergoing non-cardiac surgery. All types of hemodynamic impairment can
      be quickly assessed via TEE, and the management of the echo data can define both
      the cause and the diagnosis.

PMID- 19396055
TI  - Adopting new technologies in stroke rehabilitation: the influence of the US
      health care system.
AB  - Stroke rehabilitation is entering a new era of technological innovation,
      including the development of robotic aids for therapy, peripheral electrical
      stimulation devices, and brain stimulation systems. These technologies have the
      potential to significantly improve the efficiency and efficacy of stroke
      rehabilitation. The United States health care system creates both opportunities
      for new technologies to be created and adopted, as well as important barriers.
      Inadequate support of clinical trials of the efficacy of new non-invasive devices
      is a particular concern for practitioners seeking to determine if new devices are
      clinically useful. Government support of clinical trials of efficacy, coupled
      with reform of FDA approval processes for novel therapies, is needed to create an
      evidence-based approach to improving stroke rehabilitation.

PMID- 19396056
TI  - Are indexes of arm recovery related to daily life autonomy in patients with
      stroke?
AB  - AIM: The level of daily life autonomy in patients with stroke may be related to
      recovery of affected arm function. The aim of the study was to assess whether
      four simple bedside indexes of arm recovery can predict levels of autonomy in
      daily life activities. METHODS: A consecutive sample of 48 patients presenting
      with upper limb paresis/plegia in the acute stage after stroke was selected.
      Patients underwent five evaluation sessions at 7, 14, 30, 90 and 180 days after
      stroke. Forward stepwise multiple regression analysis was used to clarify the
      role of four potential predictors of upper limb recovery (active finger
      extension, shoulder abduction, shoulder shrug and hand movement scales).
      Dependent variables in these models were the Barthel Index score and sub-items of
      the Burke-Fahn-Marsden Scale. RESULTS: The active finger extension scale showed a
      highly significant statistical correlation with patient performance in nearly all
      outcome measures. The shoulder shrug correlated with the BI score, and with the
      dressing and hygiene Burke-Fahn-Marsden Scale sub-items. Shoulder abduction and
      hand movement scale played only a minor role. CONCLUSIONS: The active finger
      extension scale proved to be a strong early predictor of recovery of daily life
      autonomy in patients with stroke. This finding could be important in order to
      planning a specific rehabilitation treatment after the onset.

PMID- 19396057
TI  - Validation of the Brief ICF core set for low back pain from the Norwegian
      perspective.
AB  - AIM: The aim of this study was to identify candidate categories from the
      International Classification of Functioning, Disability and Health (ICF) to be
      included in the Brief ICF Core Set for low back pain (LBP) by examining their
      relation to general health and functionality. METHODS: This was part of an
      international multicentre study with 118 participating Norwegian patients with
      LBP. The Comprehensive ICF Core Set for LBP was filled in by health
      professionals. The patients reported their health-related quality of life in the
      Medical Outcome Study Short Form 36 (SF-36) and function in the Oswestry
      Disability Index. Two questions regarding the patient's general health and
      functioning were completed by the health professionals and the patients
      themselves. Regression models were developed in order to identify ICF categories
      explaining most of the variance of the criterion measures. RESULTS: Twelve ICF
      categories remained as significant explanatory factors according to the eight
      regression models, four of which were not included in a previously proposed Brief
      ICF Core Set for LBP. CONCLUSIONS: The present study complements the development
      of the Brief ICF Core Set for LBP, and indicates a minimum number of categories
      needed to explain LBP patients' functioning and health. Further elaboration of
      the Brief ICF Core Set for LBP with multinational data is needed.

PMID- 19396058
TI  - Considerations about the use and misuse of Rasch analysis in rehabilitation
      outcome studies.

PMID- 19396059
TI  - Laparoscopically assisted Hartman's reversal is an efficacious and efficient
      procedure: a case control study.
AB  - AIM: Laparoscopy may lower the mortality and morbidity rates of Hartmann's
      procedure reversal. However, it remains a challenging operation mainly due to
      adhesions of the small bowel and to the rectal stump. METHODS: We performed a
      retrospective review of 44 patients who had laparoscopic Hartmann's reversal
      (Group A). On a case-control basis, these patients were compared to 44 patients
      (Group B) who had open Hartmann's reversal. RESULTS: Preoperative patients'
      characteristics (sex, gender, BMI, ASA status, prior surgery, comorbidities,
      colonic disease) were comparable. Conversion rate in Group A was 9.1%. Operative
      incidents were comparable in both groups. Operative duration was not
      significantly shorter in Group B (195 min versus 160 min in Group B). Mortality
      rate was 2.2 % and O % in group A and B, respectively. Overall morbidity rate was
      11.4 % and 28.6 % in Group A and B, respectively (P<0.05). The mean length of
      hospital stay was significantly shorter in Group A (4.8 days) as compared to
      Group B (6.8 days), respectively. An efficiency analysis was performed and
      demonstrated that laparoscopic reversal did not generate a significant additional
      cost. CONCLUSION: Our laparoscopic technique of Hartmann's procedure reversal is
      safe and efficient. It compares positively with the same procedure performed
      openly in a case control study. Moreover, an indirect cost reduction is generated
      by the reduction of the length of hospital stay.

PMID- 19396060
TI  - Measuring near plasma membrane and global intracellular calcium dynamics in
      astrocytes.
AB  - The brain contains glial cells. Astrocytes, a type of glial cell, have long been
      known to provide a passive supportive role to neurons. However, increasing
      evidence suggests that astrocytes may also actively participate in brain function
      through functional interactions with neurons. However, many fundamental aspects
      of astrocyte biology remain controversial, unclear and/or experimentally
      unexplored. One important issue is the dynamics of intracellular calcium
      transients in astrocytes. This is relevant because calcium is well established as
      an important second messenger and because it has been proposed that astrocyte
      calcium elevations can trigger the release of transmitters from astrocytes.
      However, there has not been any detailed or satisfying description of near plasma
      membrane calcium signaling in astrocytes. Total internal reflection fluorescence
      (TIRF) microscopy is a powerful tool to analyze physiologically relevant
      signaling events within about 100 nm of the plasma membrane of live cells. Here,
      we use TIRF microscopy and describe how to monitor near plasma membrane and
      global intracellular calcium dynamics almost simultaneously. The further
      refinement and systematic application of this approach has the potential to
      inform about the precise details of astrocyte calcium signaling. A detailed
      understanding of astrocyte calcium dynamics may provide a basis to understand if,
      how, when and why astrocytes and neurons undergo calcium-dependent functional
      interactions.

PMID- 19396062
TI  - Updated evidence-based recommendations for best practices in weight loss surgery.

PMID- 19396063
TI  - Expert panel on weight loss surgery: executive report update.
AB  - Rapid shifts in the demographics and techniques of weight loss surgery (WLS) have
      led to new issues, new data, new concerns, and new challenges. In 2004, this
      journal published comprehensive evidence-based guidelines on WLS. In this issue,
      we've updated those guidelines to assure patient safety in this fast-changing
      field. WLS involves a uniquely vulnerable population in need of specialized
      resources and ongoing multidisciplinary care. Timely best-practice updates are
      required to identify new risks, develop strategies to address them, and optimize
      treatment. Findings in these reports are based on a comprehensive review of the
      most current literature on WLS; they directly link patient safety to methods for
      setting evidence-based guidelines developed from peer-reviewed scientific
      publications. Among other outcomes, these reports show that WLS reduces chronic
      disease risk factors, improves health, and confers a survival benefit on those
      who undergo it. The literature also shows that laparoscopy has displaced open
      surgery as the predominant approach; that government agencies and insurers only
      reimburse procedures performed at accredited WLS centers; that best practice care
      requires close collaboration between members of a multidisciplinary team; and
      that new and existing facilities require wide-ranging changes to accommodate
      growing numbers of severely obese patients. More than 100 specialists from across
      the state of Massachusetts and across the many disciplines involved in WLS came
      together to develop these new standards. We expect them to have far-reaching
      effects of the development of health care policy and the practice of WLS.

PMID- 19396064
TI  - Best practice updates for surgical care in weight loss surgery.
AB  - To update evidence-based best practice guidelines for surgical care in weight
      loss surgery (WLS). Systematic search of English-language literature on WLS in
      MEDLINE, EMBASE, and the Cochrane Library between April 2004 and May 2007. Use of
      key words to narrow the search for a selective review of abstracts, retrieval of
      full articles, and grading of evidence according to systems used in established
      evidence-based models. Evidence-based best practice recommendations from the most
      recent literature on surgical methods and technologies, risks and benefits,
      outcomes, and surgeon qualifications and credentialing. We identified >135
      articles; the 65 most relevant were reviewed in detail. Regular updates of
      evidence-based recommendations for best practices in WLS are required to address
      rapid changes in surgical techniques and patient demographics. Key factors in
      patient safety include surgical risk factors, type of procedure, surgeon
      training, and facility certification.

PMID- 19396066
TI  - Behavioral and psychological care in weight loss surgery: best practice update.
AB  - The objective of this study is to update evidence-based best practice guidelines
      for psychological evaluation and treatment of weight loss surgery (WLS) patients.
      We performed a systematic search of English-language literature on WLS and mental
      health, quality of life, and behavior modification published between April 2004
      and May 2007 in MEDLINE and the Cochrane Library. Key words were used to narrow
      the search for a selective review of abstracts, retrieval of full articles, and
      grading of evidence according to systems used in established evidence-based
      models. Our literature search identified 17 articles of interest; 13 of the most
      relevant were reviewed in detail. From these, we developed evidence-based best
      practice recommendations on the psychological assessment and treatment of WLS
      patients. Regular updates of evidence-based recommendations for best practices in
      psychological care are required to address the impact of mental health on short-
      and long-term outcomes after WLS. Key factors in patient safety include
      comprehensive preoperative evaluation, use of appropriate and reliable evaluation
      instruments, and the development of short- and long-term treatment plans.

PMID- 19396065
TI  - Best practice updates for multidisciplinary care in weight loss surgery.
AB  - The objective of this study is to update evidence-based best practice guidelines
      for multidisciplinary care of weight loss surgery (WLS) patients. We performed
      systematic search of English-language literature on WLS, patient selection, and
      medical, multidisciplinary, and nutritional care published between April 2004 and
      May 2007 in MEDLINE and the Cochrane Library. Key words were used to narrow the
      search for a selective review of abstracts, retrieval of full articles, and
      grading of evidence according to systems used in established evidence-based
      models. A total of 150 papers were retrieved from the literature search and 112
      were reviewed in detail. We made evidence-based best practice recommendations
      from the most recent literature on multidisciplinary care of WLS patients. New
      recommendations were developed in the areas of patient selection, medical
      evaluation, and treatment. Regular updates of evidence-based recommendations for
      best practices in multidisciplinary care are required to address changes in
      patient demographics and levels of obesity. Key factors in patient safety include
      comprehensive preoperative medical evaluation, patient education, appropriate
      perioperative care, and long-term follow-up.

PMID- 19396067
TI  - Best practice updates for informed consent and patient education in weight loss
      surgery.
AB  - To update evidence-based best practice guidelines for obtaining informed consent
      from weight loss surgery (WLS) patients, with an emphasis on appropriate content
      and communications approaches that might enhance patient understanding of the
      information, we performed a systematic search of English-language literature
      published between April 2004 and May 2007 in MEDLINE and the Cochrane database.
      Keywords included WLS and informed consent, comprehension, health literacy, and
      patient education; and WLS and outcomes, risk, patient safety management, and
      effectiveness. Recommendations are based on the most current literature and the
      consensus of the expert panel; they were graded according to systems used in
      established evidence-based models. We identified over 120 titles, 38 of which
      were reviewed in detail. Evidence suggests that WLS outcomes, including long-term
      rates of relapse, vary by procedure. For some weight loss surgeries, long-term
      outcomes may not be known. Risks also vary by patient and provider
      characteristics. Informed consent should incorporate realistic projections of the
      short- and long-term risks, benefits, and consequences of surgery, as well as
      alternatives to WLS. For consent to be informed, the education process should
      continue until the patient demonstrates comprehension of all relevant material
      and concepts. Confirmation of comprehension can protect patients engaged in the
      process of consent for WLS. Future research should focus on the outcomes and
      consequences of WLS, and different approaches that facilitate patient
      understanding of, and decision making about, WLS.

PMID- 19396068
TI  - Update on best practice recommendations for anesthetic perioperative care and
      pain management in weight loss surgery, 2004-2007.
AB  - To reevaluate and update evidence-based best practice recommendations published
      in 2004 for anesthetic perioperative care and pain management in weight loss
      surgery (WLS), we performed a systematic search of English-language literature on
      anesthetic perioperative care and pain management in WLS published between April
      2004 and May 2007 in MEDLINE and the Cochrane Library. We identified relevant
      abstracts by using key words, retrieved full text articles, and stratified the
      resulting evidence according to systems used in established evidence-based
      models. We updated prior evidence-based best practice recommendations based upon
      interim literature. In instances of controversial or inadequate scientific
      evidence, the task force reached consensus recommendations following evaluation
      of the best available information and expert opinion. The search yielded 1,788
      abstracts, with 162 potentially relevant titles; 45 were reviewed in detail.
      Despite more information on perioperative management of patients with obstructive
      sleep apnea (OSA), evidence to support preoperative testing and treatment or to
      guide perioperative monitoring is scarce. New evidence on appropriate
      intraoperative dosing of muscle relaxants allows for greater precision in their
      use during WLS. A novel application of alpha-2 agonists for perioperative
      anesthetic care is emerging. Key elements that may enhance patient safety include
      integration of the latest evidence on WLS, obesity, and collaborative
      multidisciplinary care into clinical care. However, large gaps remain in the
      evidence base.

PMID- 19396069
TI  - Best practice updates for nursing care in weight loss surgery.
AB  - The objective of this study is to update evidence-based best practice guidelines
      for nursing in weight loss surgery (WLS). We performed a systematic search of
      English-language literature on WLS and perioperative nursing, postoperative,
      anesthesia, and discharge published between April 2004 and May 2007 in MEDLINE,
      CINHAL and the Cochrane Library. Key words were used to narrow the search for a
      selective review of abstracts, retrieval of full articles, and grading of
      evidence according to systems used in established evidence-based models. From
      these, we developed evidence-based best practice recommendations from the most
      recent literature on nursing in WLS. We identified >54 papers; the most relevant
      were reviewed in detail. Regular updates of evidence-based recommendations for
      best practices in WLS nursing are required to address advances in surgery and
      anesthesiology, as well as changes in the demographics and levels of obesity in
      WLS patients. Key factors in patient safety include staff education,
      comprehensive admission assessment, patient education, careful preoperative
      surveillance and postoperative care, and long-term discharge follow-up.

PMID- 19396071
TI  - An update on best practice guidelines for specialized facilities and resources
      necessary for weight loss surgical programs.
AB  - The objective of this study is to update evidence-based best practice guidelines
      for specialized facilities and resources for weight loss surgery (WLS). We
      performed systematic search of English-language literature on WLS and facilities,
      equipment, and resources published between April 2004 and May 2007 in PubMed,
      MEDLINE, and the Cochrane Library. Keywords were used to narrow the search for a
      selective review of abstracts, retrieval of full articles, and grading of
      evidence according to systems used in established evidence-based models. Evidence
      based best practice recommendations from the most recent literature on
      specialized facilities and resources for WLS were developed. We identified 1,647
      papers in our literature search; the 46 most relevant were reviewed in detail.
      Regular updates of evidence-based recommendations for best practices in
      facilities and resources for WLS are required to address technology advances and
      growing recognition of the need for adequate equipment and specially built
      nursing units. Key factors in patient safety include availability of trained
      personnel and specialized equipment for the care of extremely obese WLS patients.

PMID- 19396070
TI  - Best practice updates for pediatric/adolescent weight loss surgery.
AB  - The objective of this study is to update evidence-based best practice guidelines
      for pediatric/adolescent weight loss surgery (WLS). We performed a systematic
      search of English-language literature on WLS and pediatric, adolescent, gastric
      bypass, laparoscopic gastric banding, and extreme obesity published between April
      2004 and May 2007 in PubMed, MEDLINE, and the Cochrane Library. Keywords were
      used to narrow the search for a selective review of abstracts, retrieval of full
      articles, and grading of evidence according to systems used in established
      evidence-based models. In light of evidence on the natural history of obesity and
      on outcomes of WLS in adolescents, guidelines for surgical treatment of obesity
      in this age group need to be updated. We recommend modification of selection
      criteria to include adolescents with BMI >or= 35 and specific obesity-related
      comorbidities for which there is clear evidence of important short-term morbidity
      (i.e., type 2 diabetes, severe steatohepatitis, pseudotumor cerebri, and moderate
      to-severe obstructive sleep apnea). In addition, WLS should be considered for
      adolescents with extreme obesity (BMI >or= 40) and other comorbidities associated
      with long-term risks. We identified >1,085 papers; 186 of the most relevant were
      reviewed in detail. Regular updates of evidence-based recommendations for best
      practices in pediatric/adolescent WLS are required to address advances in
      technology and the growing evidence base in pediatric WLS. Key considerations in
      patient safety include carefully designed criteria for patient selection,
      multidisciplinary evaluation, choice of appropriate procedure, thorough screening
      and management of comorbidities, optimization of long-term compliance, and age
      appropriate fully informed consent.

PMID- 19396072
TI  - Best practices in policy and access (coding and reimbursement) for weight loss
      surgery.
AB  - To update evidence-based best practice guidelines for coding and reimbursement
      and establish policy and access standards for weight loss surgery (WLS).
      Systematic search of English-language literature on WLS and health-care policy,
      access, insurance reimbursement, coding, private payers, public policy, and
      mandated benefits published between April 2004 and May 2007 in MEDLINE, EMBASE,
      and the Cochrane Library. Use of key words to narrow the search for a selective
      review of abstracts, retrieval of full articles, and grading of evidence
      according to systems used in established evidence-based models. We identified 51
      publications in our literature search; the 20 most relevant were examined in
      detail. These included reviews, cost-benefit analyses, and trend and cost studies
      from administrative databases. Literature on policy issues surrounding WLS are
      very sparse and largely focused on economic analyses. Reports on policy
      initiatives in the public and private arenas are primarily limited to narrative
      reviews of nonsurgical efforts to fight obesity. A substantial body of work shows
      that WLS improves or reverses most obesity-related comorbidities. Mounting
      evidence also indicates that WLS confers a significant survival advantage for
      those who undergo it. WLS is a viable and cost-effective treatment for an
      increasingly common disease, and policy decisions are more frequently being
      linked to incentives for national health-care goals. However, access to WLS often
      varies by payer and region. Currently, there are no uniform criteria for
      determining patient appropriateness for surgery.

PMID- 19396073
TI  - Best practice updates for weight loss surgery data collection.
AB  - To update evidence-based best practice guidelines for collection of data on
      weight loss surgery (WLS). Systematic search of English-language literature in
      MEDLINE and the Cochrane Library on WLS and data collection, registries, risk
      adjustment, accreditation, benchmarks, and administrative and outcomes databases
      published between April 2004 and May 2007. Use of key words to narrow the search
      for a selective review of abstracts, retrieval of full articles, and grading of
      evidence according to systems used in established evidence-based models. During
      our search, we identified 212 papers; the 63 most relevant were reviewed in
      detail. Most data collection on WLS has relied on administrative data sets,
      single-institution studies, and other sources that are not WLS specific. A six
      center, nationwide study involving data collection has been started by the
      longitudinal assessment of bariatric surgery, but results are not yet available.
      Two WLS-specific, longitudinal, national data collection systems are about to be
      implemented. Key factors in patient safety include data collection for all weight
      loss procedures; prospective, risk-adjusted, universal, benchmarked, longitudinal
      data collection systems; and use of WLS-specific data points that track clinical
      effectiveness and complications following WLS. Data collection will need to
      include assessments of novel therapies and specific subgroups (e.g., adolescents,
      the elderly, and individuals who are at the greatest risk or have the most to
      gain from WLS). Quality indicators, including metrics on processes of care and
      determination of outliers, need to be established and monitored to advance
      patient safety and quality improvement.

PMID- 19396074
TI  - Endoscopic interventions for weight loss surgery.
AB  - In this paper we review the state-of-the-art in endoscopic interventions for
      obesity treatment and make best practice recommendations for weight loss surgery
      (WLS). We performed a systematic search of English-language literature published
      between April 2004 and June 2008 in MEDLINE and the Cochrane Library on WLS and
      endoscopic interventions, endoscopically placed devices, minimally invasive
      surgery, image-guided surgery, endoluminal surgery, endoscopic instrumentation,
      interventional gastroenterology, transluminal surgery, and natural orifice
      transluminal surgery. We also searched the literature on endoscopic interventions
      and WLS and patient safety. We identified 36 pertinent articles, all of which
      were reviewed in detail; assessed the current science in endoscopic interventions
      for WLS; and made best practice recommendations based on the latest available
      evidence. Our findings indicate that endoscopic interventions and endoscopically
      placed devices may provide valuable approaches to the management of WLS
      complications and the primary management of obesity. Given the rapid changes in
      endoscopic technologies and techniques, systematic literature review is required
      to address issues related to the emerging role of endoluminal surgery in the
      treatment of obesity. These interventions should be a high priority for
      development and investigation.

PMID- 19396076
TI  - Effect of weight loss on proinflammatory state of mononuclear cells in obese
      women.

PMID- 19396077
TI  - Predictive equations for body fat in Asian Indians.

PMID- 19396079
TI  - Abdominal cavity compliance: a participant more in the building up of visceral
      obesity.

PMID- 19396080
TI  - Lack of relation between bitter taste receptor TAS2R38 and BMI in adults.

PMID- 19396082
TI  - Biased corrections or biased about corrections?

PMID- 19396085
TI  - Mantle skewness and ridge segmentation.
AB  - Mantle upwelling is generally assumed to be symmetric. Toomey et al. observe low
      seismic-wave velocity in off-axis mantle, and suggest that mantle upwelling is
      skewed, which has important implications for asthenospheric flow, ridge
      segmentation, crustal accretion, and volcanic, tectonic and hydrothermal vent
      activities along the ridge axis. However, we point out here that the mantle low
      velocity zone (MLVZ) presented by Toomey et al. is not constrained by their data.
      We conclude that inferences pertaining to ridge segmentation and mantle flow are
      not reliable.

PMID- 19396090
TI  - More than hot air.

PMID- 19396084
TI  - Prevalence of night eating in obese and nonobese twins.
AB  - The aim of this study was to assess the prevalence of night eating (NE) and
      associated symptoms in a population-based sample of Swedish twins. A total of
      21,741 individuals aged 20-47 years completed a questionnaire in 2005/2006. NE
      was defined as >/=25% of daily food intake after the evening meal and/or
      awakening at least once per week with eating episodes. The prevalence of NE was
      4.6% in men and 3.4% in women. Among obese men and women, the prevalence was 8.4
      and 7.5%, respectively. Men and women with NE had 3.4 and 3.6 times higher risk
      of binge eating compared to individuals without NE. The risk of sleep-related
      problems was 1.6-3.4 times higher in men and 2.5-3.3 times higher in women with
      NE compared to those without NE. This epidemiological study has estimated the
      prevalence of NE in a twin population. It revealed that NE is 2.5 and 2.8 times
      more common in obese men and women compared to normal weight men and women.
      Furthermore that NE is associated with binge eating and sleep-related problems.

PMID- 19396091
TI  - Wanted: cyber-czars.

PMID- 19396092
TI  - No more catch-up.

PMID- 19396099
TI  - Journal club. A neuroscientist argues for a broader approach to brain mapping.

PMID- 19396104
TI  - Pharmaceutical companies join forces on HIV.

PMID- 19396105
TI  - Still strict on stem cells.

PMID- 19396106
TI  - Fees delay pharmed drug.

PMID- 19396107
TI  - High hopes for US patent reform.

PMID- 19396108
TI  - FANTOM studies networks in cells.

PMID- 19396110
TI  - India's electioneers make bold pledges on science.

PMID- 19396111
TI  - French life-science alliance unveiled.

PMID- 19396118
TI  - Personal technology: Phoning in data.

PMID- 19396119
TI  - Stem cells: Fast and furious.

PMID- 19396121
TI  - Crystal growers are being forced to scatter.

PMID- 19396120
TI  - Struggle to translate Darwin's view of concurrency.

PMID- 19396122
TI  - Open-access publishing can survive recession.

PMID- 19396123
TI  - Big Brother has evolved.

PMID- 19396124
TI  - This title is false.

PMID- 19396130
TI  - Quantum chemistry: The little molecule that could.

PMID- 19396131
TI  - Schizophrenia: A point of disruption.

PMID- 19396132
TI  - Global change: China at the carbon crossroads.

PMID- 19396133
TI  - Complex systems: Cooperative network dynamics.

PMID- 19396134
TI  - Neuroscience: Optical control of reward.

PMID- 19396135
TI  - John Maddox (1925-2009).

PMID- 19396136
TI  - A publisher's perspective.

PMID- 19396137
TI  - Maddox by his successor.

PMID- 19396138
TI  - Solar wind as the origin of rapid reddening of asteroid surfaces.
AB  - A comparison of the laboratory reflectance spectra of meteorites with
      observations of asteroids revealed that the latter are much 'redder', with the
      spectral difference explained by 'space weathering', though the actual processes
      and timescales involved have remained controversial. A recent study of young
      asteroid families concluded that they suffered only minimal space weathering.
      Here we report additional observations of those families, revealing that space
      weathering must be a very rapid process-the final colour of a silicate-rich
      asteroid is acquired shortly after its 'birth' (within 10(6) years of undergoing
      a catastrophic collision). This rapid timescale favours solar wind implantation
      as the main mechanism of space weathering, as laboratory experiments have shown
      that it is the most rapid of several competing processes. We further demonstrate
      the necessity to take account of composition when evaluating weathering
      effectiveness, as both laboratory and asteroid data show an apparent dependence
      of weathering on olivine abundance. The rapid colour change that we find implies
      that colour trends seen among asteroids are most probably due to compositional or
      surface-particle-size properties, rather than to different relative ages.
      Apparently fresh surfaces most frequently seen among small near-Earth asteroids
      may be the result of tidal shaking that rejuvenates their surfaces during
      planetary encounters.

PMID- 19396139
TI  - Optimized dynamical decoupling in a model quantum memory.
AB  - Any quantum system, such as those used in quantum information or magnetic
      resonance, is subject to random phase errors that can dramatically affect the
      fidelity of a desired quantum operation or measurement. In the context of quantum
      information, quantum error correction techniques have been developed to correct
      these errors, but resource requirements are extraordinary. The realization of a
      physically tractable quantum information system will therefore be facilitated if
      qubit (quantum bit) error rates are far below the so-called fault-tolerance error
      threshold, predicted to be of the order of 10(-3)-10(-6). The need to realize
      such low error rates motivates a search for alternative strategies to suppress
      dephasing in quantum systems. Here we experimentally demonstrate massive
      suppression of qubit error rates by the application of optimized dynamical
      decoupling pulse sequences, using a model quantum system capable of simulating a
      variety of qubit technologies. We demonstrate an analytically derived pulse
      sequence, UDD, and find novel sequences through active, real-time experimental
      feedback. The latter sequences are tailored to maximize error suppression without
      the need for a priori knowledge of the ambient noise environment, and are capable
      of suppressing errors by orders of magnitude compared to other existing sequences
      (including the benchmark multi-pulse spin echo). Our work includes the extension
      of a treatment to predict qubit decoherence under realistic conditions, yielding
      strong agreement between experimental data and theory for arbitrary pulse
      sequences incorporating nonidealized control pulses. These results demonstrate
      the robustness of qubit memory error suppression through dynamical decoupling
      techniques across a variety of qubit technologies.

PMID- 19396140
TI  - Universal transduction scheme for nanomechanical systems based on dielectric
      forces.
AB  - Any polarizable body placed in an inhomogeneous electric field experiences a
      dielectric force. This phenomenon is well known from the macroscopic world: a
      water jet is deflected when approached by a charged object. This fundamental
      mechanism is exploited in a variety of contexts-for example, trapping microscopic
      particles in an optical tweezer, where the trapping force is controlled via the
      intensity of a laser beam, or dielectrophoresis, where electric fields are used
      to manipulate particles in liquids. Here we extend the underlying concept to the
      rapidly evolving field of nanoelectromechanical systems (NEMS). A broad range of
      possible applications are anticipated for these systems, but drive and detection
      schemes for nanomechanical motion still need to be optimized. Our approach is
      based on the application of dielectric gradient forces for the controlled and
      local transduction of NEMS. Using a set of on-chip electrodes to create an
      electric field gradient, we polarize a dielectric resonator and subject it to an
      attractive force that can be modulated at high frequencies. This universal
      actuation scheme is efficient, broadband and scalable. It also separates the
      driving scheme from the driven mechanical element, allowing for arbitrary
      polarizable materials and thus potentially ultralow dissipation NEMS. In
      addition, it enables simple voltage tuning of the mechanical resonance over a
      wide frequency range, because the dielectric force depends strongly on the
      resonator-electrode separation. We use the modulation of the resonance frequency
      to demonstrate parametric actuation. Moreover, we reverse the actuation principle
      to realize dielectric detection, thus allowing universal transduction of NEMS. We
      expect this combination to be useful both in the study of fundamental principles
      and in applications such as signal processing and sensing.

PMID- 19396141
TI  - Observation of ultralong-range Rydberg molecules.
AB  - Rydberg atoms have an electron in a state with a very high principal quantum
      number, and as a result can exhibit unusually long-range interactions. One
      example is the bonding of two such atoms by multipole forces to form Rydberg
      Rydberg molecules with very large internuclear distances. Notably, bonding
      interactions can also arise from the low-energy scattering of a Rydberg electron
      with negative scattering length from a ground-state atom. In this case, the
      scattering-induced attractive interaction binds the ground-state atom to the
      Rydberg atom at a well-localized position within the Rydberg electron
      wavefunction and thereby yields giant molecules that can have internuclear
      separations of several thousand Bohr radii. Here we report the spectroscopic
      characterization of such exotic molecular states formed by rubidium Rydberg atoms
      that are in the spherically symmetric s state and have principal quantum numbers,
      n, between 34 and 40. We find that the spectra of the vibrational ground state
      and of the first excited state of the Rydberg molecule, the rubidium dimer Rb(5s)
      Rb(ns), agree well with simple model predictions. The data allow us to extract
      the s-wave scattering length for scattering between the Rydberg electron and the
      ground-state atom, Rb(5s), in the low-energy regime (kinetic energy, <100 meV),
      and to determine the lifetimes and the polarizabilities of the Rydberg molecules.
      Given our successful characterization of s-wave bound Rydberg states, we
      anticipate that p-wave bound states, trimer states and bound states involving a
      Rydberg electron with large angular momentum-so-called trilobite molecules-will
      also be realized and directly probed in the near future.

PMID- 19396142
TI  - The carbon balance of terrestrial ecosystems in China.
AB  - Global terrestrial ecosystems absorbed carbon at a rate of 1-4 Pg yr(-1) during
      the 1980s and 1990s, offsetting 10-60 per cent of the fossil-fuel emissions. The
      regional patterns and causes of terrestrial carbon sources and sinks, however,
      remain uncertain. With increasing scientific and political interest in regional
      aspects of the global carbon cycle, there is a strong impetus to better
      understand the carbon balance of China. This is not only because China is the
      world's most populous country and the largest emitter of fossil-fuel CO(2) into
      the atmosphere, but also because it has experienced regionally distinct land-use
      histories and climate trends, which together control the carbon budget of its
      ecosystems. Here we analyse the current terrestrial carbon balance of China and
      its driving mechanisms during the 1980s and 1990s using three different methods:
      biomass and soil carbon inventories extrapolated by satellite greenness
      measurements, ecosystem models and atmospheric inversions. The three methods
      produce similar estimates of a net carbon sink in the range of 0.19-0.26 Pg
      carbon (PgC) per year, which is smaller than that in the conterminous United
      States but comparable to that in geographic Europe. We find that northeast China
      is a net source of CO(2) to the atmosphere owing to overharvesting and
      degradation of forests. By contrast, southern China accounts for more than 65 per
      cent of the carbon sink, which can be attributed to regional climate change,
      large-scale plantation programmes active since the 1980s and shrub recovery.
      Shrub recovery is identified as the most uncertain factor contributing to the
      carbon sink. Our data and model results together indicate that China's
      terrestrial ecosystems absorbed 28-37 per cent of its cumulated fossil carbon
      emissions during the 1980s and 1990s.

PMID- 19396143
TI  - Impact of changes in diffuse radiation on the global land carbon sink.
AB  - Plant photosynthesis tends to increase with irradiance. However, recent
      theoretical and observational studies have demonstrated that photosynthesis is
      also more efficient under diffuse light conditions. Changes in cloud cover or
      atmospheric aerosol loadings, arising from either volcanic or anthropogenic
      emissions, alter both the total photosynthetically active radiation reaching the
      surface and the fraction of this radiation that is diffuse, with uncertain
      overall effects on global plant productivity and the land carbon sink. Here we
      estimate the impact of variations in diffuse fraction on the land carbon sink
      using a global model modified to account for the effects of variations in both
      direct and diffuse radiation on canopy photosynthesis. We estimate that
      variations in diffuse fraction, associated largely with the 'global dimming'
      period, enhanced the land carbon sink by approximately one-quarter between 1960
      and 1999. However, under a climate mitigation scenario for the twenty-first
      century in which sulphate aerosols decline before atmospheric CO(2) is
      stabilized, this 'diffuse-radiation' fertilization effect declines rapidly to
      near zero by the end of the twenty-first century.

PMID- 19396144
TI  - The architecture of mutualistic networks minimizes competition and increases
      biodiversity.
AB  - The main theories of biodiversity either neglect species interactions or assume
      that species interact randomly with each other. However, recent empirical work
      has revealed that ecological networks are highly structured, and the lack of a
      theory that takes into account the structure of interactions precludes further
      assessment of the implications of such network patterns for biodiversity. Here we
      use a combination of analytical and empirical approaches to quantify the
      influence of network architecture on the number of coexisting species. As a case
      study we consider mutualistic networks between plants and their animal
      pollinators or seed dispersers. These networks have been found to be highly
      nested, with the more specialist species interacting only with proper subsets of
      the species that interact with the more generalist. We show that nestedness
      reduces effective interspecific competition and enhances the number of coexisting
      species. Furthermore, we show that a nested network will naturally emerge if new
      species are more likely to enter the community where they have minimal
      competitive load. Nested networks seem to occur in many biological and social
      contexts, suggesting that our results are relevant in a wide range of fields.

PMID- 19396145
TI  - A semi-aquatic Arctic mammalian carnivore from the Miocene epoch and origin of
      Pinnipedia.
AB  - Modern pinnipeds (seals, sea lions and the walrus) are semi-aquatic, generally
      marine carnivores the limbs of which have been modified into flippers. Recent
      phylogenetic studies using morphological and molecular evidence support pinniped
      monophyly, and suggest a sister relationship with ursoids (for example bears) or
      musteloids (the clade that includes skunks, badgers, weasels and otters).
      Although the position of pinnipeds within modern carnivores appears moderately
      well resolved, fossil evidence of the morphological steps leading from a
      terrestrial ancestor to the modern marine forms has been weak or contentious. The
      earliest well-represented fossil pinniped is Enaliarctos, a marine form with
      flippers, which had appeared on the northwestern shores of North America by the
      early Miocene epoch. Here we report the discovery of a nearly complete skeleton
      of a new semi-aquatic carnivore from an early Miocene lake deposit in Nunavut,
      Canada, that represents a morphological link in early pinniped evolution. The new
      taxon retains a long tail and the proportions of its fore- and hindlimbs are more
      similar to those of modern terrestrial carnivores than to modern pinnipeds.
      Morphological traits indicative of semi-aquatic adaptation include a forelimb
      with a prominent deltopectoral ridge on the humerus, a posterodorsally expanded
      scapula, a pelvis with relatively short ilium, a shortened femur and flattened
      phalanges, suggestive of webbing. The new fossil shows evidence of pinniped
      affinities and similarities to the early Oligocene Amphicticeps from Asia and the
      late Oligocene and Miocene Potamotherium from Europe. The discovery suggests that
      the evolution of pinnipeds included a freshwater transitional phase, and may
      support the hypothesis that the Arctic was an early centre of pinniped evolution.

PMID- 19396148
TI  - Testicular mixed germ cell tumors: a morphological and immunohistochemical study
      using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically
      difficult-to-classify areas.
AB  - Stem cell markers, OCT3/4, and more recently SOX2 and growth differentiation
      factor 3 (GDF3), have been reported to be expressed variably in germ cell tumors.
      We investigated the immunohistochemical expression of these markers in different
      testicular germ cell tumors, and their utility in the differential diagnosis of
      morphologically difficult-to-classify components of these tumors. A total of 50
      mixed testicular germ cell tumors, 43 also containing difficult-to-classify
      areas, were studied. In these areas, multiple morphological parameters were
      noted, and high-grade nuclear details similar to typical embryonal carcinoma were
      considered 'embryonal carcinoma-like high-grade'. Immunohistochemical staining
      for OCT3/4, c-kit, CD30, SOX2, and GDF3 was performed and graded in each
      component as 0, negative; 1+, 1-25%; 2+, 26-50%; and 3+, >50% positive staining
      cells. The different components identified in these tumors were seminoma (8),
      embryonal carcinoma (50), yolk sac tumor (40), teratoma (40), choriocarcinoma (3)
      and intra-tubular germ cell neoplasia, unclassified (35). By
      immunohistochemistry, the staining patterns were OCT3/4 -3+, all seminomas,
      embryonal carcinomas and intra-tubular germ cell neoplasia; SOX2 -3+, all
      embryonal carcinomas and -2 to 3+, 11/14 (79%) primitive neuroectodermal
      components in immature teratomas; GDF3 -2 to 3+, all yolk sac tumors, seminomas
      and intra-tubular germ cell neoplasia and 1 to 2+, 40/50 embryonal carcinomas. A
      total of 34/43 (79%) of difficult-to-classify areas stained 3+ for OCT3/4, CD30,
      and SOX2, similar to embryonal carcinoma. Among these areas, only 'embryonal
      carcinoma-like high-grade' nuclear details were significantly associated with
      such an immunophenotype. Thus, SOX2 is expressed in embryonal carcinoma and
      primitive neuroectoderm of teratoma, and unlike OCT3/4, not in intra-tubular germ
      cell neoplasia and seminoma. Therefore, it may be useful in the distinction of
      seminoma from embryonal carcinoma, and potentially in diagnosing early
      carcinomatous differentiation in seminoma. GDF3 positivity, in the absence of
      OCT3/4 and CD30, combined with morphological features, is helpful in the
      diagnosis of yolk sac tumor. 'Embryonal carcinoma-like high-grade' nuclear
      details are the most important morphological criterion for the diagnosis of
      embryonal carcinoma in difficult-to-classify areas.

PMID- 19396146
TI  - Discovery of insect and human dengue virus host factors.
AB  - Dengue fever is the most frequent arthropod-borne viral disease of humans, with
      almost half of the world's population at risk of infection. The high prevalence,
      lack of an effective vaccine, and absence of specific treatment conspire to make
      dengue fever a global public health threat. Given their compact genomes, dengue
      viruses (DENV-1-4) and other flaviviruses probably require an extensive number of
      host factors; however, only a limited number of human, and an even smaller number
      of insect host factors, have been identified. Here we identify insect host
      factors required for DENV-2 propagation, by carrying out a genome-wide RNA
      interference screen in Drosophila melanogaster cells using a well-established
      22,632 double-stranded RNA library. This screen identified 116 candidate dengue
      virus host factors (DVHFs). Although some were previously associated with
      flaviviruses (for example, V-ATPases and alpha-glucosidases), most of the DVHFs
      were newly implicated in dengue virus propagation. The dipteran DVHFs had 82
      readily recognizable human homologues and, using a targeted short-interfering-RNA
      screen, we showed that 42 of these are human DVHFs. This indicates notable
      conservation of required factors between dipteran and human hosts. This work
      suggests new approaches to control infection in the insect vector and the
      mammalian host.

PMID- 19396149
TI  - Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation
      carcinomas from other renal carcinomas.
AB  - The microphthalmia transcription factor/transcription factor E (TFE)-family
      translocation renal cell carcinomas bear specific translocations that result in
      overexpression of TFE3 or TFEB. TFE3 fusion gene product overexpression occurs as
      consequence of different translocations involving chromosome Xp11.2, whereas TFEB
      overexpression is the result of the specific translocation t(6;11)(p21;q12),
      which fuses the Alpha gene to TFEB. Both TFE3 and TFEB are closely related
      members of the microphthalmia transcription factor/TFE-family, which also
      includes TFEC and microphthalmia transcription factor. These transcription
      factors have overlapping transcriptional targets. Overexpression of
      microphthalmia transcription factor has been shown to mediate the expression of
      cathepsin-K in osteoclasts. We hypothesize that the overexpression of the related
      TFE3 fusion proteins and TFEB in translocation renal cell carcinomas may have the
      same effect. We studied cathepsin-K in 17 cytogenetically confirmed
      microphthalmia transcription factor/TFE-family translocation renal cell
      carcinomas. Seven cases showed a t(6;11)(p21;q12), ten cases showed
      translocations involving Xp11.2; five cases t(X;1)(p11;q21) resulting in a PRCC
      TFE3 gene fusion; three cases t(X;1)(p11;p34) resulting in a PSF-TFE3 gene
      fusion, one t(X;17)(p11;q25) resulting in an ASPL-TFE3 gene fusion, and one
      t(X;3)(p11;q23) with an unknown TFE3 gene fusion. As control we analyzed
      cathepsin-K in 210 clear cell, 40 papillary, 25 chromophobe renal cell carcinomas
      and 30 oncocytomas. All seven TFEB translocation renal cell carcinomas were
      labeled for cathepsin-K. Among the cytogenetically confirmed TFE3 translocation
      renal cell carcinomas, 6 out of 10 were positive. None of the other renal
      neoplasms expressed cathepsin-K. We conclude the following: (1) cathepsin-K is
      consistently and strongly expressed in TFEB translocation renal cell carcinomas
      and in 6 of 10 TFE3 translocation renal cell carcinomas. (2) Cathepsin-K
      immunolabeling in both TFE3 and TFEB translocation renal cell carcinomas
      distinguishes these neoplasms from the more common adult renal cell carcinomas,
      and may be a specific marker of these neoplasms. (3) These results further
      support the concept that the overexpression of TFE3 or TFEB in these neoplasms
      activates the expression of genes normally regulated by microphthalmia
      transcription factor in other cell types.

PMID- 19396150
TI  - Poor prognostic significance of unamplified chromosome 17 polysomy in invasive
      breast carcinoma.
AB  - The human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed
      in about 20% of breast cancers, with HER2 gene amplification responsible for
      protein overexpression in the vast majority of patients. A subset of breast
      cancers have chromosome 17 aneusomy, due to either 17 monosomy (a single copy of
      chromosome 17) or polysomy (increased copy numbers of chromosome 17). Although
      HER2 overexpression is an established adverse prognostic factor in breast cancer,
      the role of unamplified chromosome 17 polysomy is uncertain and there is a
      paucity of literature on the correlation of chromosome 17 aneusomy with important
      prognostic and predictive pathologic factors in invasive breast carcinoma.
      Furthermore, while patients showing HER2 amplification with or without polysomy
      17 are treated with trastuzumab with or without other chemotherapy, treatment of
      patients with unamplified chromosome 17 polysomy is not well defined. Currently
      most of these patients are treated similar to patients with neither amplification
      nor 17 polysomy. The aim of this study was to compare some prognostic and
      predictive factors in invasive breast carcinoma in patients with unamplified
      chromosome 17 polysomy with that seen in cases with HER2 gene amplification and
      those with neither amplification or polysomy. We found that invasive breast
      carcinomas with unamplified chromosome 17 polysomy are associated with several
      adverse prognostic indicators such as a higher nuclear grade, mitotic activity,
      Nottingham score, histologic grade, tumor stage, and greater estrogen receptor
      negativity with a trend towards the amplified group, in contrast to patients with
      neither amplification or polysomy. Although most patients with unamplified 17
      polysomy have a 2+ equivocal score on immunohistochemistry, a minority has a 3+
      positive score. An increased adverse role for unamplified polysomy along with 3+
      protein expression in some patients supports the idea that these patients should
      be considered for therapy with trastuzumab and/or anthracyclines.

PMID- 19396151
TI  - Duodenal and nodal follicular lymphomas are distinct: the former lacks activation
      induced cytidine deaminase and follicular dendritic cells despite ongoing somatic
      hypermutations.
AB  - Although most follicular lymphomas are believed to be of nodal origin, they
      sometimes originate from the duodenum. We have reported that the latter differ
      from nodal follicular lymphomas in having lower clinical stages and uniformly low
      histological grades, along with variable region of immunoglobulin heavy chain
      gene (VH) usage that is more similar to mucosa-associated lymphoid tissue (MALT)
      lymphomas. Little is known, however, about whether they possess other
      characteristics of nodal follicular lymphomas, particularly ongoing mutations
      with follicular dendritic cells. We examined 17 cases for which PCR identified
      the monoclonal bands of the immunoglobulin gene. The duodenal cases showed
      ongoing mutations, but they lacked activation-induced cytidine deaminase (AID)
      expression, a statistically significant difference from the nodal cases
      (P<0.001), and their follicular dendritic cell networks were disrupted. Moreover,
      not only were VH deviations observed but also they used very restricted VH genes.
      Although the mechanisms of ongoing mutation without AID and follicular dendritic
      cell were not clarified, restricted VH usage strongly suggested that antigen
      stimulation was involved, and that was similar to MALT lymphomas. In conclusion,
      duodenal follicular lymphomas were shown to be unique, in that they had ongoing
      hypermutations such as nodal cases, but the mechanisms involved in the
      hypermutation were quite different; furthermore, restricted VH usage suggested a
      strong similarity to the antigen-dependent origin of MALT lymphomas.

PMID- 19396152
TI  - Expression of Notch-1 and alteration of the E-cadherin/beta-catenin cell adhesion
      complex are observed in primary cutaneous neuroendocrine carcinoma (Merkel cell
      carcinoma).
AB  - Increasing evidence indicates that Notch signaling contributes to physiological
      processes, including development and differentiation, as well as tumorigenesis,
      either as a tumor promoter or suppressor, depending on cellular context,
      expression levels and cross talk with other signaling systems. Recent studies
      reported absent or minimal Notch-1 expression in neuroendocrine tumors of the
      lung and gastrointestinal tract, suggesting a tumor-suppressor function of Notch
      1. Merkel cell carcinoma is a rare and highly aggressive primary cutaneous
      neuroendocrine carcinoma. Because no information is available on Notch-1
      expression in this tumor, we have investigated a series of 31 Merkel cell
      carcinoma for Notch-1 immunoreactivity. Immunoreactivities for E-cadherin and
      beta-catenin were also analyzed. All but 1 Merkel cell carcinoma (30 of 31)
      retained cytoplasmic and membrane Notch-1 expression in more than 50% of cells.
      beta-Catenin displayed a prevalent membrane-associated staining in 30 of 31
      cases, and 22 cases showed more than 50% of immunoreactive cells whereas nuclear
      beta-catenin was seen only in 2 of 31 cases. E-cadherin membranous expression was
      remarkably low, as only 1 of 26 cases was found positive in more than 50% of
      cells. In contrast with neuroendocrine tumors in other tissues, evident Notch-1
      expression was found in Merkel cell carcinoma. This finding does not support a
      tumor-suppressor function of Notch-1 in Merkel cell carcinoma. Downregulation of
      E-cadherin and diffuse membranous beta-catenin expression suggest a dysregulation
      of the E-cadherin/beta-catenin complex in Merkel cell carcinoma. This may
      contribute to local invasion and distant metastasis.

PMID- 19396153
TI  - TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular melanomas.
AB  - The transient receptor potential cation channel, subfamily M, member 1
      (TRPM1/Melastatin-1/MLSN-1) expression has been shown to have prognostic utility
      in the evaluation of primary cutaneous melanoma. We analyzed a series of spindled
      and epithelioid cell nevi (Spitz) and primary cutaneous nodular melanomas to
      determine whether the expression of TRPM1 mRNA may be useful in distinguishing
      between Spitz nevi and nodular melanomas and to further examine the patterns of
      TRPM1 mRNA expression in cutaneous melanocytic proliferations. Formalin-fixed,
      paraffin-embedded tissues from 95 Spitz nevi and 33 nodular melanomas were
      analyzed for the expression of TRPM1 mRNA by in situ hybridization using (35)S
      labeled riboprobes. Ubiquitous melanocytic expression of TRPM1 mRNA was observed
      in 56 of 95 (59%) Spitz nevi and 4 of 33 (12%) nodular melanomas. Diffusely
      scattered loss of TRPM1 mRNA was identified in 38 of 95 (40%) Spitz nevi and 2 of
      33 (6%) nodular melanomas. Regional loss of the TRPM1 mRNA expression by a
      significant subset of dermal tumor cells or a complete absence of TRPM1
      expression by the dermal tumor was identified in 27 of 33 (82%) nodular
      melanomas, but only 1 of 95 (1%) Spitz nevi. These findings suggest that the
      pattern of TRPM1 mRNA expression may be helpful in the differentiation of Spitz
      nevi and nodular melanomas. Of the 16 patients who experienced metastasis, 15
      (94%) had primary tumors that displayed reduced MLSN mRNA expression by all or a
      part of the dermal tumor.

PMID- 19396154
TI  - Prostate cancer of transition zone origin lacks TMPRSS2-ERG gene fusion.
AB  - Recent studies have shown a unique chromosomal rearrangement that leads to the
      fusion of 5'-transmembrane protein serine proteinase-2 (TMPRSS2) with the EST
      related gene (ERG) in prostate cancer. In this study, we used fluorescence in
      situ hybridization to evaluate TMPRSS2-ERG gene fusion in prostate cancer of
      different zonal origins. Radical prostatectomy specimens with multifocal prostate
      cancer were obtained from 30 patients who were treated at our institution. Two
      separate tumor foci in each specimen, one in the peripheral zone and the other in
      the transition zone, were selected for gene fusion analysis. The selected
      peripheral zone tumor foci had a mean Gleason score of 6.8 (range, 6-7) and a
      mean tumor volume of 1.2 cm(3) (range, 0.1-4.6 cm(3)). The selected transition
      zone tumor foci had a mean Gleason score of 6.7 (range, 5-8) and a mean tumor
      volume of 4.0 cm(3) (range, 0.5-9.0 cm(3)). ERG gene rearrangement was not
      observed in any transition zone tumors; however, it was found in the peripheral
      zone tumors in 13 cases (43%). In 10 cases, the rearrangement was associated with
      the deletion of the 5'-end of ERG. In conclusion, we found that TMPRSS2-ERG gene
      fusion is associated with the zonal origin of prostate cancer. This gene fusion
      is prevalent in prostate cancer arising from the peripheral zone, but is lacking
      in prostate cancer arising from the transition zone.

PMID- 19396155
TI  - The stromal composition of mast cell aggregates in systemic mastocytosis.
AB  - Systemic mastocytosis is a stem cell disorder characterized histologically by the
      presence of multifocal compact aggregates of mast cells in at least one
      extracutaneous organ with or without evidence of skin lesions. The mast cell
      aggregates are accompanied by fibrosis, which is often significant. However, in
      spite of its frequent occurrence and severity, little is known about its
      characteristics. In this study, we evaluated the composition of the fibrotic mast
      cell aggregates by studying eight bone marrow biopsies and two spleens involved
      by systemic mastocytosis, and compared the findings with those observed in other
      fibrotic bone marrow disorders such as primary myelofibrosis and metastatic
      malignancy. Histochemistry and immunohistochemistry were used to evaluate: (a)
      extracellular matrix (reticulin, trichrome, collagen IV, laminin); (b) stromal
      reticulum cells (low-affinity nerve growth factor receptor); (c) presence of
      myofibroblastic differentiation (smooth muscle actin) and (d) microvessel density
      (CD34). We found that all cases showed marked reticulin and collagen fibrosis.
      However, unlike primary myelofibrosis and metastatic malignancy, which are
      usually associated with increased low-affinity nerve growth factor receptor
      positivity, its expression was low in all cases of systemic mastocytosis.
      Myofibroblastic differentiation was only focally detected in two of eight bone
      marrow biopsies. In all cases, the systemic mastocytosis lesions were largely
      devoid of type IV collagen and laminin. The latter findings were in contrast with
      those seen in cases of primary myelofibrosis and metastatic malignancy where
      smooth muscle actin, collagen IV and laminin were expressed in most cases. Also
      in contrast with the other two conditions, only minimal vascularity was
      detectable within the fibrotic mast cell lesions. These findings indicate that
      systemic mastocytosis exhibits a distinct pattern of stromal change, and suggest
      that the fibrogenetic mechanism in systemic mastocytosis is most likely different
      from that of other bone marrow neoplasms which are also associated with fibrosis.

PMID- 19396156
TI  - Driving fast-spiking cells induces gamma rhythm and controls sensory responses.
AB  - Cortical gamma oscillations (20-80 Hz) predict increases in focused attention,
      and failure in gamma regulation is a hallmark of neurological and psychiatric
      disease. Current theory predicts that gamma oscillations are generated by
      synchronous activity of fast-spiking inhibitory interneurons, with the resulting
      rhythmic inhibition producing neural ensemble synchrony by generating a narrow
      window for effective excitation. We causally tested these hypotheses in barrel
      cortex in vivo by targeting optogenetic manipulation selectively to fast-spiking
      interneurons. Here we show that light-driven activation of fast-spiking
      interneurons at varied frequencies (8-200 Hz) selectively amplifies gamma
      oscillations. In contrast, pyramidal neuron activation amplifies only lower
      frequency oscillations, a cell-type-specific double dissociation. We found that
      the timing of a sensory input relative to a gamma cycle determined the amplitude
      and precision of evoked responses. Our data directly support the fast-spiking
      gamma hypothesis and provide the first causal evidence that distinct network
      activity states can be induced in vivo by cell-type-specific activation.

PMID- 19396157
TI  - Select Drosophila glomeruli mediate innate olfactory attraction and aversion.
AB  - Fruitflies show robust attraction to food odours, which usually excite several
      glomeruli. To understand how the representation of such odours leads to
      behaviour, we used genetic tools to dissect the contribution of each activated
      glomerulus. Apple cider vinegar triggers robust innate attraction at a relatively
      low concentration, which activates six glomeruli. By silencing individual
      glomeruli, here we show that the absence of activity in two glomeruli, DM1 and
      VA2, markedly reduces attraction. Conversely, when each of these two glomeruli
      was selectively activated, flies showed as robust an attraction to vinegar as
      wild-type flies. Notably, a higher concentration of vinegar excites an additional
      glomerulus and is less attractive to flies. We show that activation of the extra
      glomerulus is necessary and sufficient to mediate the behavioural switch.
      Together, these results indicate that individual glomeruli, rather than the
      entire pattern of active glomeruli, mediate innate behavioural output.

PMID- 19396158
TI  - Directed transdifferentiation of mouse mesoderm to heart tissue by defined
      factors.
AB  - Heart disease is the leading cause of mortality and morbidity in the western
      world. The heart has little regenerative capacity after damage, leading to much
      interest in understanding the factors required to produce new cardiac myocytes.
      Despite a robust understanding of the molecular networks regulating cardiac
      differentiation, no single transcription factor or combination of factors has
      been shown to activate the cardiac gene program de novo in mammalian cells or
      tissues. Here we define the minimal requirements for transdifferentiation of
      mouse mesoderm to cardiac myocytes. We show that two cardiac transcription
      factors, Gata4 and Tbx5, and a cardiac-specific subunit of BAF chromatin
      remodelling complexes, Baf60c (also called Smarcd3), can direct ectopic
      differentiation of mouse mesoderm into beating cardiomyocytes, including the
      normally non-cardiogenic posterior mesoderm and the extraembryonic mesoderm of
      the amnion. Gata4 with Baf60c initiated ectopic cardiac gene expression. Addition
      of Tbx5 allowed differentiation into contracting cardiomyocytes and repression of
      non-cardiac mesodermal genes. Baf60c was essential for the ectopic cardiogenic
      activity of Gata4 and Tbx5, partly by permitting binding of Gata4 to cardiac
      genes, indicating a novel instructive role for BAF complexes in tissue-specific
      regulation. The combined function of these factors establishes a robust mechanism
      for controlling cellular differentiation, and may allow reprogramming of new
      cardiomyocytes for regenerative purposes.

PMID- 19396159
TI  - Parvalbumin neurons and gamma rhythms enhance cortical circuit performance.
AB  - Synchronized oscillations and inhibitory interneurons have important and
      interconnected roles within cortical microcircuits. In particular, interneurons
      defined by the fast-spiking phenotype and expression of the calcium-binding
      protein parvalbumin have been suggested to be involved in gamma (30-80 Hz)
      oscillations, which are hypothesized to enhance information processing. However,
      because parvalbumin interneurons cannot be selectively controlled, definitive
      tests of their functional significance in gamma oscillations, and quantitative
      assessment of the impact of parvalbumin interneurons and gamma oscillations on
      cortical circuits, have been lacking despite potentially enormous significance
      (for example, abnormalities in parvalbumin interneurons may underlie altered
      gamma-frequency synchronization and cognition in schizophrenia and autism). Here
      we use a panel of optogenetic technologies in mice to selectively modulate
      multiple distinct circuit elements in neocortex, alone or in combination. We find
      that inhibiting parvalbumin interneurons suppresses gamma oscillations in vivo,
      whereas driving these interneurons (even by means of non-rhythmic principal cell
      activity) is sufficient to generate emergent gamma-frequency rhythmicity.
      Moreover, gamma-frequency modulation of excitatory input in turn was found to
      enhance signal transmission in neocortex by reducing circuit noise and amplifying
      circuit signals, including inputs to parvalbumin interneurons. As demonstrated
      here, optogenetics opens the door to a new kind of informational analysis of
      brain function, permitting quantitative delineation of the functional
      significance of individual elements in the emergent operation and function of
      intact neural circuitry.

PMID- 19396160
TI  - Antibacterial discovery in actinomycetes strains with mutations in RNA polymerase
      or ribosomal protein S12.
AB  - We show that selection of drug-resistant bacterial mutants allows the discovery
      of antibacterial compounds. Mutant strains of a soil-isolated Streptomyces
      species that does not produce antibacterials synthesize a previously unknown
      class of antibacterial, which we name piperidamycin. Overall, 6% of non
      Streptomyces actinomycetes species and 43% of Streptomyces species that do not
      produce antibacterials are activated to produce them. The antibacterial-producing
      mutants all carried mutations in RNA polymerase and/or the ribosomal protein S12.

PMID- 19396161
TI  - Allelic imbalance sequencing reveals that single-nucleotide polymorphisms
      frequently alter microRNA-directed repression.
AB  - Genetic changes that help explain the differences between two individuals might
      create or disrupt sites complementary to microRNAs (miRNAs), but the extent to
      which such polymorphic sites influence miRNA-mediated repression is unknown.
      Here, we describe a method to measure mRNA allelic imbalances associated with a
      regulatory site found in mRNA transcribed from one allele but not found in that
      transcribed from the other. Applying this method, called allelic imbalance
      sequencing, to sites for three miRNAs (miR-1, miR-133 and miR-122) provided
      quantitative measurements of repression in vivo without altering either the
      miRNAs or their targets. A substantial fraction of polymorphic sites mediated
      repression in tissues that expressed the cognate miRNA, and downregulation was
      correlated with site type and site context. Extrapolating these results to the
      other broadly conserved miRNAs suggests that when comparing two mouse strains (or
      two human individuals), polymorphic miRNA sites cause expression of many genes
      (often hundreds) to differ.

PMID- 19396162
TI  - Electric modulation of conduction in multiferroic Ca-doped BiFeO3 films.
AB  - Many interesting materials phenomena such as the emergence of high-Tc
      superconductivity in the cuprates and colossal magnetoresistance in the
      manganites arise out of a doping-driven competition between energetically similar
      ground states. Doped multiferroics present a tantalizing evolution of this
      generic concept of phase competition. Here, we present the observation of an
      electronic conductor-insulator transition by control of band-filling in the model
      antiferromagnetic ferroelectric BiFeO3 through Ca doping. Application of electric
      field enables us to control and manipulate this electronic transition to the
      extent that a p-n junction can be created, erased and inverted in this material.
      A 'dome-like' feature in the doping dependence of the ferroelectric transition is
      observed around a Ca concentration of approximately 1/8, where a new pseudo
      tetragonal phase appears and the electric modulation of conduction is optimized.
      Possible mechanisms for the observed effects are discussed on the basis of the
      interplay of ionic and electronic conduction. This observation opens the door to
      merging magnetoelectrics and magnetoelectronics at room temperature by combining
      electronic conduction with electric and magnetic degrees of freedom already
      present in the multiferroic BiFeO3.

PMID- 19396163
TI  - PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled
      by inhibitor-1 and PP1 phosphorylation.
AB  - Loss of cell division cycle 2 (Cdc2, also known as Cdk1) activity after cyclin B
      degradation is necessary, but not sufficient, for mitotic exit. Proteins
      phosphorylated by Cdc2 and downstream mitotic kinases must be dephosphorylated.
      We report here that protein phosphatase-1 (PP1) is the main catalyst of mitotic
      phosphoprotein dephosphorylation. Suppression of PP1 during early mitosis is
      maintained through dual inhibition by Cdc2 phosphorylation and the binding of
      inhibitor-1. Protein kinase A (PKA) phosphorylates inhibitor-1, mediating binding
      to PP1. As Cdc2 levels drop after cyclin B degradation, auto-dephosphorylation of
      PP1 at its Cdc2 phosphorylation site (Thr 320) allows partial PP1 activation.
      This promotes PP1-regulated dephosphorylation at the activating site of inhibitor
      1 (Thr 35) followed by dissociation of the inhibitor-1-PP1 complex and then full
      PP1 activation to promote mitotic exit. Thus, Cdc2 both phosphorylates multiple
      mitotic substrates and inhibits their PP1-mediated dephosphorylation.

PMID- 19396164
TI  - RAD18 transmits DNA damage signalling to elicit homologous recombination repair.
AB  - To maintain genome stability, cells respond to DNA damage by activating
      signalling pathways that govern cell-cycle checkpoints and initiate DNA repair.
      Cell-cycle checkpoint controls should connect with DNA repair processes, however,
      exactly how such coordination occurs in vivo is largely unknown. Here we describe
      a new role for the E3 ligase RAD18 as the integral component in translating the
      damage response signal to orchestrate homologous recombination repair (HRR). We
      show that RAD18 promotes homologous recombination in a manner strictly dependent
      on its ability to be recruited to sites of DNA breaks and that this recruitment
      relies on a well-defined DNA damage signalling pathway mediated by another E3
      ligase, RNF8. We further demonstrate that RAD18 functions as an adaptor to
      facilitate homologous recombination through direct interaction with the
      recombinase RAD51C. Together, our data uncovers RAD18 as a key factor that
      orchestrates HRR through surveillance of the DNA damage signal.

PMID- 19396165
TI  - A precise form of divisive suppression supports  population coding in the primary
      visual cortex.
AB  - The responses of neurons in the primary visual cortex (V1) to an optimally
      oriented grating are suppressed when a non-optimal grating is superimposed.
      Although cross-orientation suppression is thought to reflect mechanisms that
      maintain a distributed code for orientation, the effect of superimposed gratings
      on V1 population responses is unknown. Using intrinsic signal optical imaging, we
      found that patterns of tree shrew V1 activity evoked by superimposed equal
      contrast gratings were predicted by the averages of patterns evoked by individual
      component gratings. This prediction held across contrasts, for summed sinusoidal
      gratings or nonsumming square-wave gratings, and was evident in single-unit
      extracellular recordings. Intracellular recordings revealed consistent levels of
      suppression throughout the time course of subthreshold responses. These results
      indicate that divisive suppression powerfully governs population responses to
      multiple orientations. Moreover, the specific form of suppression that we
      observed appears to support independent population codes for stimulus orientation
      and strength and calls for a reassessment of mechanisms that underlie cross
      orientation suppression.

PMID- 19396166
TI  - Circular analysis in systems neuroscience: the dangers of double dipping.
AB  - A neuroscientific experiment typically generates a large amount of data, of which
      only a small fraction is analyzed in detail and presented in a publication.
      However, selection among noisy measurements can render circular an otherwise
      appropriate analysis and invalidate results. Here we argue that systems
      neuroscience needs to adjust some widespread practices to avoid the circularity
      that can arise from selection. In particular, 'double dipping', the use of the
      same dataset for selection and selective analysis, will give distorted
      descriptive statistics and invalid statistical inference whenever the results
      statistics are not inherently independent of the selection criteria under the
      null hypothesis. To demonstrate the problem, we apply widely used analyses to
      noise data known to not contain the experimental effects in question. Spurious
      effects can appear in the context of both univariate activation analysis and
      multivariate pattern-information analysis. We suggest a policy for avoiding
      circularity.

PMID- 19396167
TI  - Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate
      oncogenesis.
AB  - The TMPRSS2-ERG fusion, present in approximately 50% of prostate cancers, is less
      common in prostatic intraepithelial neoplasia (PIN), raising questions about
      whether TMPRSS2-ERG contributes to disease initiation. We identified the
      translational start site of a common TMPRSS2-ERG fusion and showed that
      transgenic TMPRSS2-ERG mice develop PIN, but only in the context of PI3-kinase
      pathway activation. TMPRSS2-ERG-positive human tumors are also enriched for PTEN
      loss, suggesting cooperation in prostate tumorigenesis.

PMID- 19396168
TI  - Aberrant ERG expression cooperates with loss of PTEN to promote cancer
      progression in the prostate.
AB  - Chromosomal translocations involving the ERG locus are frequent events in human
      prostate cancer pathogenesis; however, the biological role of aberrant ERG
      expression is controversial. Here we show that aberrant expression of ERG is a
      progression event in prostate tumorigenesis. We find that prostate cancer
      specimens containing the TMPRSS2-ERG rearrangement are significantly enriched for
      loss of the tumor suppressor PTEN. In concordance with these findings, transgenic
      overexpression of ERG in mouse prostate tissue promotes marked acceleration and
      progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to
      prostatic adenocarcinoma in a Pten heterozygous background. In vitro
      overexpression of ERG promotes cell migration, a property necessary for
      tumorigenesis, without affecting proliferation. ADAMTS1 and CXCR4, two candidate
      genes strongly associated with cell migration, were upregulated in the presence
      of ERG overexpression. Thus, ERG has a distinct role in prostate cancer
      progression and cooperates with PTEN haploinsufficiency to promote progression of
      HGPIN to invasive adenocarcinoma.

PMID- 19396169
TI  - A large-scale genome-wide association study of Asian populations uncovers genetic
      factors influencing eight quantitative traits.
AB  - To identify genetic factors influencing quantitative traits of biomedical
      importance, we conducted a genome-wide association study in 8,842 samples from
      population-based cohorts recruited in Korea. For height and body mass index, most
      variants detected overlapped those reported in European samples. For the other
      traits examined, replication of promising GWAS signals in 7,861 independent
      Korean samples identified six previously unknown loci. For pulse rate, signals
      reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2.9
      x 10(-9)) and 6q22 (rs12110693, P = 1.6 x 10(-9)), with the latter approximately
      400 kb from the coding sequence of GJA1. For systolic blood pressure, the most
      compelling association involved chromosome 12q21 and variants near the ATP2B1
      gene (rs17249754, P = 1.3 x 10(-7)). For waist-hip ratio, variants on chromosome
      12q24 (rs2074356, P = 7.8 x 10(-12)) showed convincing associations, although no
      regional transcript has strong biological candidacy. Finally, we identified two
      loci influencing bone mineral density at multiple sites. On chromosome 7q31,
      rs7776725 (within the FAM3C gene) was associated with bone density at the radius
      (P = 1.0 x 10(-11)), tibia (P = 1.6 x 10(-6)) and heel (P = 1.9 x 10(-10)). On
      chromosome 7p14, rs1721400 (mapping close to SFRP4, a frizzled protein gene)
      showed consistent associations at the same three sites (P = 2.2 x 10(-3), P = 1.4
      x 10(-7) and P = 6.0 x 10(-4), respectively). This large-scale GWA analysis of
      well-characterized Korean population-based samples highlights previously unknown
      biological pathways.

PMID- 19396170
TI  - A conserved structural motif mediates formation of the periplasmic rings in the
      type III secretion system.
AB  - The type III secretion system (T3SS) is a macromolecular 'injectisome' that
      allows bacterial pathogens to transport virulence proteins into the eukaryotic
      host cell. This macromolecular complex is composed of connected ring-like
      structures that span both bacterial membranes. The crystal structures of the
      periplasmic domain of the outer membrane secretin EscC and the inner membrane
      protein PrgH reveal the conservation of a modular fold among the three proteins
      that form the outer membrane and inner membrane rings of the T3SS. This leads to
      the hypothesis that this conserved fold provides a common ring-building motif
      that allows for the assembly of the variably sized outer membrane and inner
      membrane rings characteristic of the T3SS. Using an integrated structural and
      experimental approach, we generated ring models for the periplasmic domain of
      EscC and placed them in the context of the assembled T3SS, providing evidence for
      direct interaction between the outer membrane and inner membrane ring components
      and an unprecedented span of the outer membrane secretin.

PMID- 19396171
TI  - Three-dimensional reconstruction of the Shigella T3SS transmembrane regions
      reveals 12-fold symmetry and novel features throughout.
AB  - Type III secretion systems (T3SSs) mediate bacterial protein translocation into
      eukaryotic cells, a process essential for virulence of many Gram-negative
      pathogens. They are composed of a cytoplasmic secretion machinery and a base that
      bridges both bacterial membranes, into which a hollow, external needle is
      embedded. When isolated, the latter two parts are termed the 'needle complex'. An
      incomplete understanding of the structure of the needle complex has hampered
      studies of T3SS function. To estimate the stoichiometry of its components, we
      measured the mass of its subdomains by scanning transmission electron microscopy
      (STEM). We determined subunit symmetries by analysis of top and side views within
      negatively stained samples in low-dose transmission electron microscopy (TEM).
      Application of 12-fold symmetry allowed generation of a 21-25-A resolution, three
      dimensional reconstruction of the needle complex base, revealing many new
      features and permitting tentative docking of the crystal structure of EscJ, an
      inner membrane component.

PMID- 19396172
TI  - Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that
      mediates DNA synapsis.
AB  - The products of recombination-activating genes RAG1 and RAG2 mediate the assembly
      of antigen receptor genes during lymphocyte development in a process known as
      V(D)J recombination. Lack of structural information for the RAG proteins has
      hindered mechanistic studies of this reaction. We report here the crystal
      structure of an essential DNA binding domain of the RAG1 catalytic core bound to
      its nonamer DNA recognition motif. The RAG1 nonamer binding domain (NBD) forms a
      tightly interwoven dimer that binds and synapses two nonamer elements, with each
      NBD making contact with both DNA molecules. Biochemical and biophysical
      experiments confirm that the two nonamers are in close proximity in the RAG1/2
      DNA synaptic complex and demonstrate the functional importance of the protein-DNA
      contacts revealed in the structure. These findings reveal a previously
      unsuspected function for the NBD in DNA synapsis and have implications for the
      regulation of DNA binding and cleavage by RAG1 and RAG2.

PMID- 19396173
TI  - Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte
      extravasation into the brain.
AB  - Specific inhibition of the entry of encephalitogenic T lymphocytes into the
      central nervous system in multiple sclerosis would provide a means of inhibiting
      disease without compromising innate immune responses. We show here that targeting
      lymphocyte interactions with endothelial basement membrane laminins provides such
      a possibility. In mouse experimental autoimmune encephalomyelitis, T lymphocyte
      extravasation correlates with sites expressing laminin alpha4 and small amounts
      of laminin alpha5. In mice lacking laminin alpha4, laminin alpha5 is ubiquitously
      expressed along the vascular tree, resulting in marked and selective reduction of
      T lymphocyte infiltration into the brain and reduced disease susceptibility and
      severity. Vessel phenotype and immune response were not affected in these mice.
      Rather, laminin alpha5 directly inhibited integrin alpha(6)beta(1)-mediated
      migration of T lymphocytes through laminin alpha4. The data indicate that T
      lymphocytes use mechanisms distinct from other immune cells to penetrate the
      endothelial basement membrane barrier, permitting specific targeting of this
      immune cell population.

PMID- 19396174
TI  - Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to
      enhance immunotherapies.
AB  - Identifying key factors that enhance immune responses is crucial for manipulating
      immunity to tumors. We show that after a vaccine-induced immune response,
      adjuvant interleukin-7 (IL-7) improves antitumor responses and survival in an
      animal model. The improved immune response is associated with increased IL-6
      production and augmented T helper type 17 cell differentiation. Furthermore, IL-7
      modulates the expression of two ubiquitin ligases: Casitas B-lineage lymphoma b
      (Cbl-b), a negative regulator of T cell activation, is repressed, and SMAD
      specific E3 ubiquitin protein ligase-2 (Smurf2) is enhanced, which antagonizes
      transforming growth factor-beta signaling. Notably, we show that although short
      term IL-7 therapy potently enhances vaccine-mediated immunity, in the absence of
      vaccination it is inefficient in promoting antitumor immune responses, despite
      inducing homeostatic proliferation of T cells. The ability of adjuvant IL-7 to
      antagonize inhibitory networks at the cellular and molecular level has major
      implications for immunotherapy in the treatment of tumors.

PMID- 19396175
TI  - Chromosome instability is common in human cleavage-stage embryos.
AB  - Chromosome instability is a hallmark of tumorigenesis. This study establishes
      that chromosome instability is also common during early human embryogenesis. A
      new array-based method allowed screening of genome-wide copy number and loss of
      heterozygosity in single cells. This revealed not only mosaicism for whole
      chromosome aneuploidies and uniparental disomies in most cleavage-stage embryos
      but also frequent segmental deletions, duplications and amplifications that were
      reciprocal in sister blastomeres, implying the occurrence of breakage-fusion
      bridge cycles. This explains the low human fecundity and identifies post-zygotic
      chromosome instability as a leading cause of constitutional chromosomal
      disorders.

PMID- 19396176
TI  - Green fluorescent proteins are light-induced electron donors.
AB  - Proteins of the green fluorescent protein (GFP) family are well known owing to
      their unique biochemistry and extensive use as in vivo markers. We discovered
      that GFPs of diverse origins can act as light-induced electron donors in
      photochemical reactions with various electron acceptors, including biologically
      relevant ones. Moreover, via green-to-red GFP photoconversion, this process can
      be observed in living cells without additional treatment.

PMID- 19396177
TI  - FTIR analysis of GPCR activation using azido probes.
AB  - We demonstrate the site-directed incorporation of an IR-active amino acid, p
      azido-L-phenylalanine (azidoF, 1), into the G protein-coupled receptor rhodopsin
      using amber codon suppression technology. The antisymmetric stretch vibration of
      the azido group absorbs at approximately 2,100 cm(-1) in a clear spectral window
      and is sensitive to its electrostatic environment. We used FTIR difference
      spectroscopy to monitor the azido probe and show that the electrostatic
      environments of specific interhelical networks change during receptor activation.

PMID- 19396179
TI  - A new screening assay for allosteric inhibitors of cSrc.
AB  - Targeting kinases outside the highly conserved ATP pocket is thought to be a
      promising strategy for overcoming bottlenecks in kinase inhibitor research, such
      as limited selectivity and drug resistance. Here we report the development and
      application of a direct binding assay to detect small molecules that stabilize
      the inactive conformation of the tyrosine kinase cSrc. Protein X-ray
      crystallography validated the assay results and confirmed an exclusively
      allosteric binding mode.

PMID- 19396178
TI  - Impact of linker strain and flexibility in the design of a fragment-based
      inhibitor.
AB  - The linking together of molecular fragments that bind to adjacent sites on an
      enzyme can lead to high-affinity inhibitors. Ideally, this strategy would use
      linkers that do not perturb the optimal binding geometries of the fragments and
      do not have excessive conformational flexibility that would increase the entropic
      penalty of binding. In reality, these aims are seldom realized owing to
      limitations in linker chemistry. Here we systematically explore the energetic and
      structural effects of rigid and flexible linkers on the binding of a fragment
      based inhibitor of human uracil DNA glycosylase. Analysis of the free energies of
      binding in combination with cocrystal structures shows that the flexibility and
      strain of a given linker can have a substantial impact on binding affinity even
      when the binding fragments are optimally positioned. Such effects are not
      apparent from inspection of structures and underscore the importance of linker
      optimization in fragment-based drug discovery efforts.

PMID- 19396180
TI  - A black swan?

PMID- 19396182
TI  - Fragmented present.

PMID- 19396181
TI  - Paediatric practices.

PMID- 19396183
TI  - Own brand products.

PMID- 19396184
TI  - Care for all.

PMID- 19396185
TI  - Enjoyable elevators.

PMID- 19396186
TI  - Gutka consumption.

PMID- 19396188
TI  - Improved child protection training needed.

PMID- 19396199
TI  - Digital dental photography. Part 1: an overview.
AB  - This paper is the first article in a new ten-part series on digital dental
      photography. Part 1 previews and outlines the contents of the subsequent papers
      and in addition, defines the aims and objectives of a digital dental image and
      the features that are required for an ideal intra-oral picture.

PMID- 19396200
TI  - Safeguarding children in dentistry: 1. Child protection training, experience and
      practice of dental professionals with an interest in paediatric dentistry.
AB  - Following several highly publicised inquiries into the deaths of children from
      abuse and neglect, there has been much recent interest in the role and
      responsibility of all health professionals to protect children at risk of
      maltreatment. The findings of a postal questionnaire, sent in March 2005 to 789
      dentists and dental care professionals with an interest in paediatric dentistry
      working in varied settings in the UK, are presented in a two-part report and
      discussed in the context of current multi-agency good practice in safeguarding
      and promoting the welfare of children. This first part explores reported child
      protection training, experience and practice. There was a significant gap between
      recognising signs of abuse and responding effectively: 67% of respondents had
      suspected abuse or neglect of a child patient at some time in their career but
      only 29% had ever made a child protection referral. The dental profession is
      alerted to the need to ensure necessary appropriate action to safeguard children
      is always taken when child abuse or neglect are suspected.

PMID- 19396207
TI  - Dental health and disease in ancient Egypt.
AB  - In ancient Egypt the exceptionally dry climate together with the unique burial
      customs has resulted in the survival of large numbers of well-preserved skeletal
      and mummified remains. Examinations of these remains together with an analysis of
      the surviving documentary, archaeological and ethnographic evidence has enabled a
      detailed picture of the dental health of these ancient people to be revealed,
      perhaps more so than for any other civilisation in antiquity. In this, the first
      of two articles, the dental pathological conditions that afflicted the ancient
      Egyptians is considered. The commonest finding is that of tooth wear, which was
      often so excessive that it resulted in pulpal exposure. Multiple abscesses were
      frequently seen, but caries was not a significant problem. Overall the findings
      indicate that the various pathological conditions and non-pathological
      abnormalities of teeth evident in dentitions in the twenty-first century were
      also manifest in ancient Egypt, although the incidences of these conditions
      varies considerably between the civilisations.

PMID- 19396208
TI  - Travelling for teeth: characteristics and perspectives of dental care tourism in
      Hungary.
AB  - BACKGROUND AND AIM: Despite quite lively debates about dental care tourism,
      scientific studies into the size and the characteristics of the phenomenon remain
      widely lacking. The present study is the first to measure the phenomenon in one
      of the most prominent destination countries, Hungary, with a particular focus on
      the Western Hungarian region and the capital Budapest. METHOD: A questionnaire
      has been sent to dentists in these regions. The response rate is 25.3% in Western
      Hungary and 20.7% in Budapest. RESULTS: According to the survey, patients from
      neighbouring countries dominate dental care tourism in the border regions of
      Western Hungary, while Budapest attracts more patients from countries further
      away. In terms of motivation, dentists regard relative price levels but also
      service considerations as being of major importance for patients coming to
      Hungary for dental care. CONCLUSION: The study confirms Hungary as a centre for
      dental care tourism, attracting patients from bordering countries but also
      patients travelling longer distances. Price levels have been a major factor
      making Hungary an international treatment destination. With price differences
      narrowing down, broader service quality is increasingly emphasised as a selling
      strategy.

PMID- 19396227
TI  - Marching for science.

PMID- 19396229
TI  - Carrot sticks or joysticks: video games improve vision.

PMID- 19396230
TI  - Bottoms up: transduction channels at tip link bases.

PMID- 19396231
TI  - Inhibition by an excitatory conductance: a paradox explained.

PMID- 19396232
TI  - The secret language of siblings.

PMID- 19396233
TI  - Motoneurons buckling under stress.

PMID- 19396234
TI  - Inhibition of Listeria monocytogenes by a combination of chitosan and divergicin
      M35.
AB  - The antimicrobial activities of the class IIa bacteriocin divergicin M35 and
      several types of chitosan against Listeria monocytogenes were quantified by agar
      diffusion, critical micro-dilution, and viable count and observed by electron
      microscopy. Antimicrobial activity of chitosan depended on its molecular mass
      (MM) and the pH. Three chitosans with MM values of 2, 20, and 100 kDa and 87.4%
      degree of deacetylation (DDA) were chosen for further study, based on high anti
      listerial activity at pH 4.5. Electron microscopy suggested that the mechanism of
      anti-listerial activity also varied with the MM. Low-MM chitosan appeared to
      inhibit L. monocytogenes by affecting cell permeability and growth, whereas
      medium- and high-MM chitosan may form a barrier on the cell surface that prevents
      entry of nutrients. The minimum inhibitory concentrations (MICs) of 2, 20, and
      100 kDa chitosan and divergicin M35 against a divergicin-resistant strain of L.
      monocytogenes (LSD 535) were 2.5, 2.5, 0.625, and 0.25 mg/mL, respectively. The
      combination of any of these 3 chitosans and divergicin M35 appeared to have an
      additive effect against L. monocytogenes, as determined by fractional inhibitory
      concentration (FIC) index. This study provides useful data for the development of
      chitosan films incorporating divergicin M35 for inhibiting L. monocytogenes in
      foods.

PMID- 19396235
TI  - Chitinase and beta-1,3-glucanase enzyme production by the mycoparasite
      Clonostachys rosea f. catenulata against fungal plant pathogens.
AB  - Clonostachys rosea f. catenulata (syn. Gliocladium catenulatum) is an effective
      fungal biological agent against Fusarium root and stem rot and Pythium damping
      off diseases on cucumber plants. Both chitinase and beta-1,3-glucanase enzymes
      were produced when C. rosea was grown on a synthetic medium containing chitin or
      laminarin as a sole carbon source, respectively. Chitinase production was also
      induced by Fusarium cell walls, while beta-1,3-glucanase activity was induced by
      both Fusarium and Pythium cell walls, as well as by growth on homogenized
      cucumber roots and on low-carbon media. Mycelial growth of Fusarium and Pythium,
      when exposed to C. rosea culture filtrates that contain glucanase activity, was
      significantly reduced compared with the controls, and cell walls of both
      pathogens were degraded. On excised cucumber roots, hyphae of C. rosea formed
      appressorium-like structures and coiled around hyphae of Pythium. In culture, C.
      rosea caused localized degradation of Fusarium hyphae. Cucumber root tissues
      colonized by C. rosea showed higher levels of beta-1,3-glucanase activity at 7
      days post-application compared with untreated controls. To determine if this
      activity was derived from C. rosea, glucanase isoforms were separated on activity
      gels. Fungal culture filtrates and root extracts contained the same predominant
      20 kDa isoform. Reverse-transcription polymerase chain reaction (RT-PCR) using
      primers designed to amplify a beta-1,3-glucanase gene in C. rosea confirmed
      glucanase expression on roots. These results show that C. rosea produces beta-1,3
      glucanase in situ, which can degrade hyphae of Fusarium and Pythium and
      contribute to biological control efficacy.

PMID- 19396236
TI  - ALT1-encoded alanine aminotransferase plays a central role in the metabolism of
      alanine in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, the paralogous genes ALT1 and ALT2 have
      been proposed to encode alanine aminotransferase isozymes. Although in other
      microorganisms this enzyme constitutes the main pathway for alanine biosynthesis,
      its role in S. cerevisiae had remained unclear. Results presented in this paper
      show that under respiratory conditions, Alt1p constitutes the sole pathway for
      alanine biosynthesis and catabolism, constituting the first example of an alanine
      aminotransferase that simultaneously carries out both functions. Conversely,
      under fermentative conditions, it plays a catabolic role and alanine is mainly
      synthesized through an alternative pathway. It can thus be concluded that ALT1
      has functions in alanine biosynthesis and utilization or only alanine utilization
      under respiratory and fermentative conditions, respectively. ALT2 expression was
      repressed under all tested conditions, suggesting that Alt2p biosynthesis is
      strictly controlled and only allowed to express under peculiar physiological
      conditions.

PMID- 19396237
TI  - Characterization of bacterial and fungal communities in composted biosolids over
      a 2 year period using denaturing gradient gel electrophoresis.
AB  - Composting is a microbial process that converts organic waste into a nutrient
      rich end product used in horticultural and agricultural applications. The
      diversity and long-term succession of microorganisms found in composted biosolids
      has been less characterized than other composts. In this study, bacterial and
      fungal communities found in composted biosolids aging from 1 to 24 months were
      studied using denaturing gradient gel electrophoresis (DGGE) and sequencing. The
      results revealed high levels of diversity, where 53 bacterial species belonging
      to 10 phyla and 21 fungal species belonging to 4 phyla were identified.
      Significant differences were observed when comparing the bacterial DGGE patterns
      of young compost samples, whereas no differences were observed in samples over 8
      months. For fungal patterns, no significant differences were observed during the
      first 4 months of composting, but the diversity then significantly shifted until
      24 months. The results indicate that patterns of bacterial species vary during
      the first few months of composting, whereas fungal patterns generally vary
      throughout the whole process, except during early stages. The description of the
      main microbial groups found in composted biosolids could find various
      applications, including the discovery of biotechnologically relevant
      microorganisms and the development of novel markers allowing quantitative
      monitoring of key microorganisms.

PMID- 19396238
TI  - The effect of plant growth-promoting rhizobacteria on asparagus seedlings and
      germinating seeds subjected to water stress under greenhouse conditions.
AB  - Plant growth-promoting rhizobacteria (PGPR) can have positive effects on vigour
      and productivity, especially under stress conditions. In asparagus (Asparagus
      officinalis L.) field culture, seeds are planted in high-density nurseries, and 1
      year-old crowns are transplanted to production fields. Performance can be
      negatively affected by water stress, transplant shock, and disease pressure on
      wounded roots. PGPR inoculation has the potential to alleviate some of the
      stresses incurred in the production system. In this study, the effects of PGPR
      (Pseudomonas spp.) treatment were determined on 3-week-old greenhouse-grown
      seedlings and germinating seeds of 2 asparagus cultivars. The pots were irrigated
      to a predetermined level that resulted in optimum growth or the plants were
      subjected to drought or flooding stress for 8 weeks. The cultivars responded
      differently to PGPR: single inoculations of seedlings enhanced growth of 'Guelph
      Millennium' under optimum conditions and 'Jersey Giant' seedlings under drought
      stress. Seed inoculations with PGPR resulted in a positive response only for
      'Guelph Millennium', for which both single or multiple inoculations enhanced
      plant growth under drought stress.

PMID- 19396239
TI  - Molecular and biochemical characterization of Iranian surfactin-producing
      Bacillus subtilis isolates and evaluation of their biocontrol potential against
      Aspergillus flavus and Colletotrichum gloeosporioides.
AB  - The characterization of surfactin-producing Bacillus subtilis isolates collected
      from different ecological zones of Iran is presented. Characterization was
      performed using blood agar, PCR, drop-collapse, and reverse-phase high
      performance liquid chromatography (HPLC) analyses, and the isolates' biocontrol
      effects against the aflatoxin-producing agent Aspergillus flavus and the citrus
      antracnosis agent Colletotrichum gloeosporioides were studied. In total, 290 B.
      subtilis isolates were isolated from phylosphere and rhizosphere samples
      collected from fields and gardens of 5 provinces of Iran. Blood agar assays
      showed that 185 isolates produced different biosurfactants. Isolates containing
      the sfp gene, coding for surfactin, were detected using the PCR method. It was
      found that 14 different isolates contained the sfp gene. Drop-collapse assays,
      which detect isolates with high production of surfactin, showed that 7 isolates
      produced high levels of surfactin. It was found from HPLC analysis that the
      isolates containin the sfp gene produced between 55 and 1610 mg of surfactin per
      litre of broth medium. Four isolates, named BS119m, BS116l, N3dn, and BS113c,
      produced more than 1000 mg of surfactin per litre of broth. The highest surfactin
      production level was observed for isolate BS119m (1610 mg/L). The antagonistic
      potential of the sfp gene-containing isolates was determined using dual culture
      and chloroform vapour methods. Our bioassay results indicated that isolate BS119m
      showed high inhibitory effects against A. flavus (100%) and C. gloeosporioides
      (88%). Furthermore, the effect of purified surfactin on the growth of A. flavus
      was evaluated. Mycelia growth was considerably reduced with increasing
      concentration of surfactin, and 36%, 54%, 84%, and 100% inhibitions of mycelia
      growth were, respectively, observed at 20, 40, 80, and 160 mg/L after 7 days of
      incubation.

PMID- 19396240
TI  - Evaluation of nitrogenous media components by Plackett-Burman statistical design
      for beta-d-fructofuranosidase production by Saccharomyces sp. strain GVT263.
AB  - beta-d-Fructofuranosidase (FFase), an important enzyme of the confectionery and
      fructose syrup industry, is produced by several microorganisms. However, yeasts
      are the most used source because of their high sucrose fermentation capacity. In
      this work, production of FFase was carried out in submerged fermentation using a
      high enzyme-producing yeast strain. Plackett-Burman statistical experimental
      design was applied to evaluate the fermentation medium components. The effects of
      10 nitrogen sources were studied in a 16-run experimental design. Beef extract,
      yeast extract, N-Z-amine, tryptone, meat extract, and ammonium acetate were found
      to have significant effects on enzyme production. Among these, yeast extract, N-Z
      amine, and ammonium acetate were the most significant. A maximum FFase activity
      of 299.4 U/mL was obtained after a 24 h fermentation period.

PMID- 19396241
TI  - Enumeration of the contaminating bacterial microbiota in unfermented pasteurized
      milks enriched with probiotic bacteria.
AB  - Pasteurized and unfermented milks supplemented with probiotic bacteria are
      appearing on the market. It then becomes a challenge to ascertain the undesirable
      contamination microbiota in the presence of a largely superior population of
      probiotic bacteria. A method to enumerate the contaminating microbial microbiota
      in such probiotic-enriched milks was developed. The probiotic cultures,
      Lactobacillus rhamnosus Lb-Immuni-T and Bifidobacterium animalis subsp. lactis BB
      12(R), were added to a pasteurized unfermented milk to reach a minimum of 1
      billion CFU per 250 mL portion, as ascertained by plating on de Man - Rogosa -
      Sharpe (MRS) agar in anaerobic conditions. No growth of B. animalis subsp. lactis
      BB-12 was noted on plate count agar (PCA) or Petrifilm plates, and the presence
      of this culture did not affect standard plate counts (SPC) of contaminating
      bacteria. However, L. rhamnosus formed colonies on PCA and Petrifilm plates.
      Attempts were thus made to inhibit the growth of the probiotic lactobacilli in
      PCA. The addition of 2% sodium phosphate (SP) or 5% glycerophosphate (GP)
      inhibited the growth of the lactobacilli in broths, but pin-point colonies of L.
      rhamnosus Lb-Immuni-T nevertheless appeared on PCA supplemented with phosphates.
      SPC could be obtained on PCA + 2% SP by only counting the large colonies, but
      this resulted in a significant (4.4 fold) underestimation of SPC values. On
      Petrifilm AC, at dilutions 0 to 2, all colonies were considered as being
      contaminants, while at dilutions 3 and 4, only large colonies were counted for
      SPC determinations. There was a direct correlation (R2 = 0.99) between SPC values
      with Petrifilm in uninoculated milks and those obtained on probiotic-enriched
      milks. The high correlation obtained over the 102 to 106 CFU/mL range of SPC
      values show that this Petrifilm method is appropriate to evaluate the
      microbiological quality of pasteurized milks enriched with L. rhamnosus Lb-Immuni
      T and B. animalis subsp. lactis BB-12.

PMID- 19396242
TI  - Fungi from two forests of southern India: a comparative study of endophytes,
      phellophytes, and leaf litter fungi.
AB  - The species diversity and distribution of 3 ecological groups of fungi (viz.,
      foliar endophytes, phellophytes, and leaf litter fungi of 6 tree hosts of a dry
      thorn forest and 6 tree hosts of an evergreen forest of southern India) were
      studied. As the methods of sampling and the isolation procedure were maintained
      constant, the results could be compared across hosts and fungal assemblages. The
      diversity of endophytes was less in both forests, owing to host recurrence. The
      litter fungi showed a higher diversity in both forests when compared with
      endophytes or phellophytes. There was little overlap between the species
      assemblages of the 3 ecological groups of fungi. Hence, to be cost effective,
      diversity estimation exercises for fungi in the tropics should include different
      fungal substrates rather than one substrate (or ecological group); it appears
      that even small sample sizes of different substrates would provide an
      approximation that is the near-real species diversity, rather than using large
      sample sizes of any one particular indicator group of fungi.

PMID- 19396243
TI  - Production and biochemical and molecular characterization of a keratinolytic
      serine protease from chicken feather-degrading Bacillus licheniformis RPk.
AB  - A novel feather-degrading bacterium was isolated from a polluted river and
      identified as Bacillus licheniformis RPk. The isolate exhibited high proteinase
      production when grown in chicken-feather media. Complete feather degradation was
      achieved during cultivation. Maximum protease activity (4150 U/mL with casein as
      a substrate and 37.35 U/mL with keratin as a substrate) was obtained when the
      strain was grown in a medium containing 7.5 g/L chicken feathers, 2 g/L yeast
      extract, 0.5 g/L NaCl, 0.1 g/L MgSO4 x 7H2O, 0.7 g/L KH2PO4, and 1.4 g/L K2HPO4
      for 48 h with agitation of 200 rev/min at 37 degrees C. The major protease
      produced by B. licheniformis RPk was purified to homogeneity by a 3-step
      procedure. The molecular mass of the purified enzyme was estimated to be 32 kDa
      by SDS-PAGE and gel filtration. The optimum pH and temperature for the
      caseinolytic activity were around 11.0 and 65 degrees C, respectively. The
      optimum pH and temperature for the keratinolytic activity were 9.0 and 60 degrees
      C, respectively. The activity of the enzyme was totally lost in the presence of
      phenylmethylsulfonyl fluoride, which suggests that the purified enzyme is a
      serine protease. The thermostability of the enzyme was considerably enhanced in
      the presence of Ca2+ at temperatures >50 degrees C. The kerRP gene, which encodes
      the keratinolytic protease, was isolated, and its DNA sequence was determined.
      The deduced amino acid sequence revealed that the keratinase KerRP differs from
      KerA of B. licheniformis PWD-1, subtilisin Carlsberg, and keratinase of B.
      licheniformis by 2, 4, and 62 amino acids, respectively.

PMID- 19396244
TI  - Dibutylphthalate and Tween 80 alter ultrastructure in Candida albicans:
      implications for peroxisome proliferation.
AB  - Phthalates are ubiquitous environmental pollutants associated with endocrine
      disruption and peroxisome proliferation in experimental animals. In yeasts
      exposed to environmental chemicals, including phthalates, alterations in cell
      growth, cellular morphology, and H2O2 detoxification occur. Nutrient availability
      also influences diverse cellular processes. Differences in responses to
      environmental stress between Candida albicans and the model yeast, Saccharomyces
      cerevesiae, have been reported. In this study, we chose C. albicans as an
      alternate model for testing estrogen-like chemicals because of its high affinity
      estrogen-binding protein and, in contrast to S. cerevesiae, estrogens are not
      growth inhibitory for C. albicans. Cultures were grown in either yeast nitrogen
      dextrose (YND; phosphate limiting) or YNDP (YND plus 100 mmol/L inorganic
      phosphate). For chemical testing, 0.5% dibutylphthalate (DBP), 0.05% Tween 80, or
      a combination of the two (DBPT) were incorporated in growth media to investigate
      the effects of these estrogenic agents on cell proliferation, morphology, and
      catalase demonstration. We observed significant differences in cell growth
      related to DBP and changes in cell wall thickness related to both Tween 80 and
      phosphate. We describe ultrastructural changes including detachment of the outer
      yeast cell wall layer and presence of putative peroxisomes. Our findings support
      the proposal that C. albicans may be particularly suitable for use in studies
      involving cellular responses associated with exposure to estrogenic chemicals
      contained in complex mixtures.

PMID- 19396245
TI  - The role of heparan sulfate on adhesion of 47 and 51 kDa outer membrane proteins
      of Helicobacter pylori to gastric cancer cells.
AB  - Helicobacter pylori is a common gastrointestinal pathogenic bacterium in humans
      and the usual preference for the stomach's outer membrane proteins (OMPs) are
      antigens involved in the adhesion process. Through SDS-PAGE and blotting
      analyses, using horseradish peroxidase-labeled heparan sulfate (HRP-HS) as a
      probe, we identified H. pylori OMPs with affinity for heparan sulfate (OMP-HS).
      Biotin-streptavidin bacterial-adhesion assay was used to evaluate participation
      of OMP-HS in the adhesion of H. pylori to semi-confluent HeLa S3 and Kato III
      cell monolayers. The results provide evidence that induction of antibodies
      against 2 OMP-HSs (HSBP-47 and HSBP-51) could reduce binding of H. pylori to both
      cell lines and induce detachment of cell-bound bacteria from infected cultured
      cells.

PMID- 19396246
TI  - Construction and analysis of pathogenicity island deletion mutants of Erwinia
      amylovora.
AB  - An easy gene-knockout technique, PCR-based one-step inactivation of chromosomal
      genes, is widely used in Escherichia coli and related enterobacteria to construct
      mutants. In this study, we adapted this technique to construct genomic island and
      large operon deletion mutants of Erwinia amylovora, including the 33.4 kb hrp
      type III secretion (T3SS) pathogenicity island (PAI1) and the 15.8 kb amylovoran
      biosynthesis (AMS) operon. Deletion of 2 novel T3SS pathogenicity islands (PAI2
      and PAI3) and an operon encoding a type II secretion system (T2SS) demonstrated
      that these determinants are not involved in virulence in plants. Co-inoculation
      experiments demonstrated that the hrp-T3SS and AMS deletion mutants could
      complement each other. These results further confirmed that the one-step
      inactivation technique can be used to generate large deletions in E. amylovora.

PMID- 19396247
TI  - Visualization of sporopollenin-containing pathogenic green micro-alga Prototheca
      wickerhamii by fluorescent in situ hybridization (FISH).
AB  - Fluorescent in situ hybridization (FISH) using taxon-specific, rRNA-targeted
      oligonucleotide probes is one of the most powerful tools for the rapid
      identification of harmful microorganisms. However, eukaryotic algal cells do not
      always allow FISH probes to permeate over their cell walls. Members of the
      pathogenic micro-algal genus Prototheca are characterized by their distinctive
      cell-wall component, sporopollenin, an extremely tough biopolymer that resists
      acid and alkaline hydrolysis, enzyme attack, and acetolysis. To our knowledge,
      there has been no report of the successful permeation by the oligonucleotide
      probes over the cell walls of unicellular green micro-algae, which contain
      sporopollenin. The DNA probes passed through the cell wall of Prototheca
      wickerhamii after treating the algal cells with cetyltrimethylammonium bromide
      (CTAB). Most cells in the middle logarithmic growth phase culture fluoresced when
      hybridized with the rRNA-targeted universal probe for eukaryotes, though
      individual cells included in this culture differed in the level of cell-wall
      vulnerability to attack by the polysaccharide-degrading enzyme, thus reflecting
      the different stages of the life cycle. This is the first report regarding the
      visualization of sporopollenin-containing, green micro-algal cells by FISH.

PMID- 19396248
TI  - Editorial.
AB  - What's real and what isn't? This seems to us a useful framework for a year-end
      look at Optics Express. From viewpoints that are either too close or too distant,
      perceptions of reality can be distorted, and sometimes a reality check is needed.
      Let's say that the inside view of Optics Express is the one the Editorial Board
      and the OSA staff have, and the outside view is the one readers, authors and
      reviewers have. From both sides achievements and shortfalls are evident.

PMID- 19396249
TI  - Introduction.
AB  - This is a time of significant efforts in the development and investigation of
      physical and technical problems related to laser diodes (LD) and their
      applications. During the last few years astonishing progress in the performance
      of a wide set of parameters has been achieved. The output of laser diode bar on a
      level of more than 100 watts was demonstrated, different schemes of efficient
      phase locking have been investigated, and perspective approaches in realization
      of various optical configurations of LD pumped solid state lasers (SSL) were
      introduced. At the same time the existing level of development still is far from
      physical limits. The capability of semiconductor advanced technologies, heat
      transfer modes realization, and wide spectral range SSL materials development
      appears to be very promising. The task of this Focus Issue of Optics Express is
      to show the contemporary status of the above-mentioned problems and to attract
      the attention of the laser community to the new opportunities with wide range of
      applications.

PMID- 19396250
TI  - High performance laser diode bars with aluminum-free active regions.
AB  - We present operating and lifetest data on 795 and 808 nm bars with aluminum-free
      active regions. Conductively cooled bars operate reliably at CW power outputs of
      40 W, and have high efficiency, low beam divergence, and narrow spectra. Record
      CW powers of 115 W CW are demonstrated at 795 nm for 30% fill-factor bars mounted
      on microchannel coolers. We also review QCW performance and lifetime for higher
      fill-factor bars processed on identical epitaxial material.

PMID- 19396251
TI  - Diode-pumped high-efficiency Tm:YAG lasers.
AB  - Eye-safe solid-state lasers that operate at 2 mm wavelength have many
      applications in medical, remote sensing and military technologies. With a 3-W CW
      laser-diode pumping, we obtained 760 mW 2.01 mm Tm:YAG laser under CW operation.
      The slope efficiency was 44% and the optical to optical efficiency reached 36%.
      In the acousto-optic Q-switched operation, laser pulses with the energy of 1.2mJ
      and 380 ns FWHM width have been achieved.

PMID- 19396252
TI  - Phase-locking of the 2D structures.
AB  - Experimental results on 1D and 2D phase-locking of laser diode arrays are
      presented. Attention is paid to the employment of the arrays consisting of wide
      aperture lasers diodes. Selection of the "in-phase" supermode, preferable for
      most of the cases, is attained in the external quarter Talbot (Lc=ZT/4=d 2 /2l)
      cavity due to the output mirror tilt at the angle jm=l/2d. Analysis of the
      parameters that influence on the phase-locking is given. Our experiments confirm
      theoretical predictions of the system stability and adequate selectivity for the
      laser diode array fill factor (FF) FF=0.6.

PMID- 19396253
TI  - Intensification of heat transfer in high-power laser diode bars by means of
      porous metal heat-sink.
AB  - To intensify a heat transfer in high-power emitters based on laser diode bars we
      propose the use of a heat sink from a porous permeable material cooled by a fluid
      flow [1-3]. The main advantage of this class of materials is the possibility of
      removing significant heat flows with compact heat sink. An analysis of the
      characteristic values of the thermal loads and their relations with the material
      and liquid parameters drawn from an one-dimensional model of stationary one-sided
      heat exchange shows the possibility of heat flow removal of more than 1.5 kW/cm 2
      at room temperature in a liquid. Methods for improving the effectiveness of the
      strategy are considered.

PMID- 19396254
TI  - Statistical texture synthesis of mammographic images with super-blob lumpy
      backgrounds.
AB  - Realistic anatomical images are useful for assessment and improvement of medical
      image quality. The use of synthesized images has the advantage of providing the
      user with a large number of independent samples, in a controlled environment. We
      propose a method to generate medical textures that are fully defined by a set of
      adjustable parameters and a random number generator, and which statistical
      properties are analytically tractable. This method, called the "clustered lumpy
      background", is a generalization of the original lumpy background described by
      Rolland and Barrett (1992). A detailed application of the method in the case of
      mammography is presented. It is shown that the synthesized images are visually
      very similar and that their first and second order statistics can be considered
      as being equivalent.

PMID- 19396255
TI  - Introduction.
AB  - During the last decade the use of laser radiation has grown far beyond its
      traditional role as a convenient, bright and spectrally narrow source of light.
      In particular, the coherence properties of the radiation have been put to use for
      very detailed and fine work in spectroscopy, collision dynamics and the
      manipulation of both the internal structure and the center of mass motion of
      atoms and molecules. These are the key words describing the work program of the
      research network "Laser Controlled Dynamics of Molecular Processes and
      Applications (ERB-CHR-XTC-94-0603),' established by the European Union under the
      program "Human Capital and Mobility (HCM)' with the intent of sending young
      researchers (postdocs and students) across national borders within the European
      Union.

PMID- 19396256
TI  - Excitation of C60 using a chirped free electron laser.
AB  - Gas phase C60 is resonantly excited using picosecond infrared (IR) pulses from a
      free electron laser. The excitation can be very high, reaching levels where the
      thermal emission of electrons from C60 is observed. The excitation is much more
      efficient when the IR radiation is chirped to lower frequencies during the
      excitation process. The excitation process is modeled and the results are
      compared to the experiment.

PMID- 19396257
TI  - SF6 scattering from graphite surfaces: comparison of effects induced by thermal
      and laser controlled vibrational excitation.
AB  - We report scattering experiments of multiphoton vibrationally excited SF6
      molecules from graphite surfaces demonstrating ro-vibrational excitation in the
      collision. The beam scattering experiments were carried out at different initial
      kinematic conditions and as a function of the surface temperature. The energy
      transfer depends both on the initial state of the molecule and on the momentum
      transferred as well as on the temperature of the surface. The role of surface
      atomic corrugation is evidenced.

PMID- 19396258
TI  - Laser-controlled adsorption of Na atoms in evanescent wave spectroscopy.
AB  - A new spectroscopic technique for studying adsorption of atoms at a transparent
      dielectric surface is exploited. A quantitative comparison of the Autler-Townes
      splitting in measured and calculated, surface temperature-dependent two-photon
      evanescent wave spectra provides values of the adsorption energy, the
      preexponential factor for the rate of desorption and the polarizability of alkali
      atoms, adsorbed on a glass surface. It is speculated that this technique could
      form the basis for future two-photon control of atoms close to dielectric
      surfaces.

PMID- 19396259
TI  - Slow molecule detection or Ramsey fringes in two-photon spectroscopy: which is
      better for high resolution spectroscopy and metrology ?
AB  - The CO2 laser locked onto a saturated absorption resonance of OsO4 provides a
      secondary frequency standard in the 10 mm region, with an accuracy of 50 Hz to 1
      kHz. For averaging times less than 100 s its stability performance is better than
      the Hydrogen maser. This paper deals with the present attempt to increase this
      performance by using a two-photon molecular resonance as a reference. We begin
      with some preliminary and promising results on a two-photon line of SF6 leading
      to characteristics similar to those obtained with a saturation line of OsO4 .
      Then two alternative methods to increase the resolution are presented : optical
      detection of slow molecules and a new development of the well-known Ramsey
      fringes. Metrological features are analyzed for both methods.

PMID- 19396260
TI  - Novel laser controlled variable matter wave beamsplitter.
AB  - We demonstrate a novel variable beam splitter using a tripod-linkage of atomic
      states, the physics of which is based on the laser control of the non-adiabatic
      coupling between two degenerate dark states. This coupling and the splitting
      ratio is determined by the time delay of the interaction induced by two of the
      laser beams.

PMID- 19396261
TI  - Floquet perturbative analysis for STIRAP beyond the rotating wave approximation.
AB  - We present a perturbative analysis of Floquet eigenstates in the context of two
      delayed laser processes (STIRAP) in three level systems. We show the efficiency
      of a systematic perturbative development which can be applied as long as no non
      linear resonances occur.

PMID- 19396262
TI  - Complete population transfer to and from a continuum and the radiative
      association of cold Na atoms to produce translationally cold Na2 molecules in
      specific vib-rotational states.
AB  - We demonstrate the feasibility of a laser induced complete population transfer to
      and from a continuum of states. We study the two-photon dissociation of v = 28; J
      = 1,...,10 sodium dimers. We demonstrate that using just a pair of "counter
      intuitively" ordered pulses we can dissociate 100% of the molecules in an
      ensemble. The scheme is shown to be stable with respect to the initial choice of
      rotational level and to fluctuations in the laser frequency and intensity. We
      also study the reverse phenomenon of complete population transfer from the
      continuum. We perform calculations on the radiative association of Na atoms to
      form the Na2 molecule in specific vib-rotational states. It is shown that two
      pulses of 20 nsec duration and as little as 6 MW/cm 2 peak power can photo
      associate more than 98% of the atoms within a (pulse and velocity determined)
      relative effective distance, to yield Na2 molecules in the chosen v = 28; J = 10
      vib-rotational state. This means that given a density of 10 16 atoms/cm 3 and a
      temperature of 7K, a 10Hz pulsed laser source of the above parameters can con-
      vert half of all the Na atoms in the ensemble to v = 28; J = 10 Na2 molecules
      within 15 seconds of operation.

PMID- 19396263
TI  - Electromagnetically induced transparency and coherent-state preparation in
      optically thick media.
AB  - The preparation of an optically dense ensemble of three- level systems in dark
      states of the interaction with coherent radiation is discussed. It is shown that
      methods involving spontaneous emissions of photons such as Raman optical pumping
      fail to work beyond a critical density due to multiple scattering and trapping of
      these photons and the associated decay of the dark state(s). In optically thick
      media coherent-state preparation is only possible by entirely coherent means such
      as stimulated Raman adiabatic passage (STIRAP). It is shown that STIRAP is the
      underlying physical mechanism for electromagnetically induced transparency (EIT).

PMID- 19396264
TI  - Coherent writing and reading of information using frequency-chirped short
      bichromatic laser pulses.
AB  - We propose to use the sensitivity of the population transfer in three-level L
      atoms to the relative phases and amplitudes of frequency-chirped short
      bichromatic laser pulses for coherent, fast and robust storage and processing of
      phase or intensity optical information. The information is being written into the
      excited state population which in a second step is transferred in a fast and
      robust way into a nondecaying storage level. It is shown that an arbitrary
      superposition of the ground states can be generated by controlling the relative
      phase between the laser pulses.

PMID- 19396266
TI  - New feature announcement.
AB  - SPATIAL AND POLARIZATION DYNAMICS OF SEMICONDUCTOR LASERS: Special Joint Issue of
      the Journal of the Optical Society of America B and Optics Express Feature
      announcement.

PMID- 19396265
TI  - High-intensity pulse propagation in semiconductors: on-resonant self-induced
      transmission and effects in the continuum.
AB  - We perform high-intensity pulse propagation experiments in semiconductors. On a
      free exciton resonance, we demonstrate coherent Self-Induced Transmission. Tuning
      the laser towards higher energy, thus exciting continuum states, the degree of
      transmission is reduced. The pulse breakup vanishes. Increasing the pulse
      intensity by several orders of magnitude, pulse breakup can be observed again.

PMID- 19396267
TI  - Numerical experiments with optical pulses in V-type media.
AB  - We present the results of a series of numerical experiments on the propagation of
      pairs of coupled short optical pulses in media with inhomogeneous broadening. The
      main results apply to propagation in three-level media in the V configuration.

PMID- 19396268
TI  - Discussion to the equivalent point realized by the two polarized beams in AOTF
      system.
AB  - By an accurate theoretical analysis, an equivalent point is found where the
      filtered optic wave lengths of the two acoustic-optic reactions of "e in o out"
      and "o in e out" are the same with the same acoustic frequency. Two cases of d=0
      and d10 are discussed and compared. The merits of the equivalent point is
      discussed in different points of view. The discussions conclude that the
      parameters set around the equivalent point leading to the optimum designing.

PMID- 19396269
TI  - Performance of GaAs smart pixel components before and after monolithic
      integration of InGaP LEDs using Epitaxy-on-Electronics technology.
AB  - Smart pixel technology provides the ability to integrate complex electronic
      circuitry with optoelectronic devices to produce signal processing capabilities
      previously unattainable with a single technology. Epitaxy-on-Electronics (EoE) is
      a process by which optoelectronic devices are monolithically integrated with
      electronic circuitry in a common semiconductor material. Here, InGaP LEDs are
      integrated with GaAs electronic circuitry to produce smart pixel arrays. In this
      paper, the architecture and experimental characterization of the optical devices
      of a novel smart pixel implementation of an neural network are presented.
      Measured performance characteristics are presented for the detectors and LEDs,
      before and after the EoE process. The experimental results demonstrate
      limitations in the performance of the detectors and LEDs for use in a full-scale
      implementation, however, current ongoing improvements in the EoE technology show
      promise to eliminate these limitations.

PMID- 19396270
TI  - Finite beam curvature related patterns in a saturable medium.
AB  - We study numerically the effects of finite curvature and ellipticity of the
      Gaussian beam on propagation through a saturating nonlinear medium. We
      demonstrate generation of different types of pattern arising from the input phase
      structure as well as the phase structure imparted by the nonlinear medium.

PMID- 19396271
TI  - Enhanced light amplification due to group-velocity anomaly peculiar to two- and
      three-dimensional photonic crystals.
AB  - An analytical expression was derived for light amplification by stimulated
      emission in arbitrary photonic crystals, which showed and enhancement due to
      small group velocity. This enhancement was evaluated quantitatively for a two
      dimensional crystal with a finite thickness, and an extremely large enhancement
      due to group-velocity anomaly peculiar to two- and three-dimensional crystals was
      found even for quite a thin crystal.

PMID- 19396272
TI  - Iridescent color of a shell of the mollusk pinctada margaritifera caused by
      diffraction.
AB  - Shells and pearls often show iridescent color. The cause of this phenomenon has
      been attributed to diffraction, both diffraction and interference, or
      interference alone. We used a shell of the mollusk Pinctada margaritifera, which
      shows very strong iridescent colors, to study how this color is produced in the
      layers of nacre in shells. From observations with a scanning electronic
      microscope (SEM), this particular shell exhibits a very fine scale diffraction
      grating structure. This suggests that the iridescent color is caused by
      diffraction, which was demonstrated by an experiment using an argon ion laser
      illuminating the shell to produce a distinct diffraction image. The strength of
      the iridescent color can be correlated to both the groove density of the
      diffraction grating formed by the shell, and the surface quality of the grooves
      themselves. A shell with a high groove density and a smooth groove surface
      produces a strong iridescent color.

PMID- 19396273
TI  - Optical parametric oscillator with non-ideal mirrors and single- and multi-mode
      pump beams.
AB  - Residual re ections of the idler wave in nominally singly resonant optical
      parametric oscillators can lead to uctuations in the output because the
      parametric conversion process is sensitive to the phases of the re ected waves.
      The energy fluctuations in a pulsed optical parametric oscillator are studied
      experimentally and numerically for single- or multi-longitudinal mode pump beams.
      We find that the fluctuations are reduced by a multi-mode pump so this may be
      preferable when unwanted re ections are present. We also observe that the
      parametric conversion process leads to serious self-focusing of the pump beam,
      and this limits the maximum safe pump energy.

PMID- 19396274
TI  - Feature stabilized digital x-ray coronary angiograms improve human visual
      detection in JPEG compressed images.
AB  - We evaluate the effect on human visual detection of a display method that
      stabilizes the motion of the feature of interest in sequential JPEG compressed x
      ray coronary angiogram images. At all levels of image compression the feature
      stabilized display significantly improved performance with respect to the
      standard display where the artery is moving. In addition, for both the moving
      artery and stabilized display, human performance with images compressed at 15:1
      was not significantly different from performance with the uncompressed images.

PMID- 19396275
TI  - Polarized wavelength-dependent measurements of turbid media.
AB  - Wavelength-dependent, polarized, elastic-scatter spectra of tissue phantoms and
      in vitro tissue are presented. These measurements are shown to be sensitive to
      very small changes in composition of the scattering medium. A simple physical
      explanation of the wavelength-dependent polarization phenomena observed for media
      consisting only of spherical particles is given and the relevance of wavelength
      dependent, polarized, elastic-scatter spectra to in vivo applications are
      discussed.

PMID- 19396276
TI  - Perfect following in the diabatic limit.
AB  - We present the theory of optical excitation of a two-level quantum system, using
      an interaction Hamiltonian that permits both adiabatic following and diabatic
      following.

PMID- 19396277
TI  - Power dependence of dynamic spatial replenishment of femtosecond pulses
      propagating in air.
AB  - Numerical simulations of nonlinear pulse propagation in air show an initial pulse
      formed, absorbed by plasma generation, and subsequently replenished by power from
      the trailing edge. Here we show that this scenario implies that the length scale
      for filament propagation is relatively insensitive to the peak input power beyond
      the threshold for filament generation.

PMID- 19396278
TI  - Finite beam curvature related patterns in asaturable medium: errata.
AB  - The value of Delta in Fig. 7 and Fig. 8 was wrongly printed.

PMID- 19396279
TI  - Introduction.
AB  - In the past decade, near-infrared sampling of tissue has become a large field of
      study, which has been called by many names (Photon migration, photon random walk,
      photon density waves, photon diffusion) encompassing work in spectroscopy and
      imaging of tissue. In this special issue, the focus is on diffuse optical
      tomography as it applies to medicine and biology. Diffuse optical tomography
      involves processing of near-infrared light measurements taken from tissue to
      create images of the interior.

PMID- 19396280
TI  - Diffuse optical 3D-slice imaging of bounded turbid media using a new integro
      differential equation.
AB  - A new integro-differential equation for diffuse photon density waves (DPDW) is
      derived within the diffusion approximation. The new equation applies to
      inhomogeneous bounded turbid media. Interestingly, it does not contain any terms
      involving gradients of the light diffusion coefficient. The integro-differential
      equation for diffusive waves is used to develop a 3D-slice imaging algorithm
      based the on angular spectrum representation in the parallel plate geometry. The
      algorithm may be useful for near infrared optical imaging of breast tissue, and
      is applicable to other diagnostics such as ultrasound and microwave imaging.

PMID- 19396281
TI  - Optical image reconstruction based on the third-order diffusion equations.
AB  - This paper presents a third-order diffusion equations-based optical image
      reconstruction algorithm. The algorithm has been implemented using finite element
      discretizations coupled with a hybrid regularization that combines both Marquardt
      and Tikhonov schemes. Numerical examples are used to compare between the third-
      and first-order reconstructions. The results show that the third-order
      reconstruction codes are more stable than the first-order codes, and are capable
      of reconstructing void-like regions. From the examples given, it has also been
      shown that the first-order codes fail to both qualitatively and quantitatively
      reconstruct the void-like regions.

PMID- 19396282
TI  - Algorithms for 3D localization and imaging using near-field diffraction
      tomography with diffuse light.
AB  - We introduce two filtering methods for near-field diffuse light diffraction
      tomography based on the angular spectrum representation. We then combine these
      filtering techniques with a new method to find the approximate depth of the image
      heterogeneities. Taken together these ideas improve the fidelity of our
      projection image reconstructions, provide an interesting three dimensional
      rendering of the reconstructed volume, and enable us to identify and classify
      image artifacts that need to be controlled better for tissue applications. The
      analysis is accomplished using data derived from numerical finite difference
      simulations with added noise.

PMID- 19396283
TI  - Optical tomography using the SCIRun problem solving environment: Preliminary
      results for three-dimensional geometries and parallel processing.
AB  - We present a 3D implementation of the UCL imaging package for absorption and
      scatter reconstruction from time-resolved data (TOAST), embedded in the SCIRun
      interactive simulation and visualization package developed at the University of
      Utah. SCIRun is a scientific programming environment that allows the interactive
      donstruction, debugging, and steering of large-scale scientific computations.
      Using this "computational workbench," a scientist can design and modify
      simulations interactively via a dataflow programming model. SCIRun enables
      scientists to design and modify model geometry, interactively change simulation
      parameters and boundary condititions, and interactively visualize geometric
      models and simulation results. Reconstruction of a segmented 3D head model is
      used as an example for demonstrating the capabilities of the combined
      TOAST/SCIRun approach.

PMID- 19396284
TI  - Comparison of imaging geometries for diffuse optical tomography of tissue.
AB  - Images produced in six different geometries with diffuse optical tomography
      simulations of tissue have been compared using a finite element-based algorithm
      with iterative refinement provided by the Newton-Raphson approach. The source
      detector arrangements studied include (i) fan-beam tomography, (ii) full
      reflectance and transmittance tomography, as well as (iii) sub-surface imaging,
      where each of these three were examined in a circular and a flat slab geometry.
      The algorithm can provide quantitatively accurate results for all of the
      tomographic geometries investigated under certain circumstances. For example,
      quantitatively accurate results occur with sub-surface imaging only when the
      object to be imaged is fully contained within the diffuse projections. In general
      the diffuse projections must sample all regions around the target to be
      characterized in order for the algorithm to recover quantitatively accurate
      results. Not only is it important to sample the whole space, but maximal angular
      sampling is required for optimal image reconstruction. Geometries which do not
      maximize the possible sampling angles cause more noise artifact in the
      reconstructed images. Preliminary simulations using a mesh of the human brain
      confirm that optimal images are produced from circularly symmetric source
      detector distributions, but that quantitatively accurate images can be
      reconstructed even with a sub-surface imaging, although spatial resolution is
      modest.

PMID- 19396285
TI  - Design and evaluation of a continuous-wave diffuse optical tomography system.
AB  - Diffuse optical tomography (DOT) can image spatial variations in highly
      scattering optical media. We have built an inexpensive and portable continuous
      wave DOT system containing 18 laser diode sources (9 at 780nm and 9 at 830nm) and
      16 silicon detectors, which can acquire 288 independent measurements in less than
      4 seconds. These data can then be processed using a variety of imaging
      algorithms. We first discuss the design of diffuse imaging equipment in general,
      and then describe our instrument, along with the technical issues that influenced
      its design. The technical challenges involved in performing DOT over large optode
      areas are discussed. We also present rat brain measurements following electrical
      forepaw stimulation using DOT. These results clearly demonstrate the capabilities
      of DOT and set the stage for advancement to quantitative functional brain
      imaging.

PMID- 19396286
TI  - Systematic diffuse optical image errors resulting from uncertainty in the
      background optical properties.
AB  - We investigated the diffuse optical image errors resulting from systematic errors
      in the background scattering and absorption coefficients, Gaussian noise in the
      measurements, and the depth at which the image is reconstructed when using a 2D
      linear reconstruction algorithm for a 3D object. The fourth Born perturbation
      approach was used to generate reflectance measurements and k-space tomography was
      used for the reconstruction. Our simulations using both single and dual
      wavelengths show large systematic errors in the absolute reconstructed absorption
      coefficients and corresponding hemoglobin concentrations, while the errors in the
      relative oxy- and deoxy- hemoglobin concentrations are acceptable. The greatest
      difference arises from a systematic error in the depth at which an image is
      reconstructed. While an absolute reconstruction of the hemoglobin concentrations
      can deviate by 100% for a depth error of n1 mm, the error in the relative
      concentrations is less than 5%. These results demonstrate that while quantitative
      diffuse optical tomography is difficult, images of the relative concentrations of
      oxy- and deoxy-hemoglobin are accurate and robust. Other results, not presented,
      confirm that these findings hold for other linear reconstruction techniques (i.e.
      SVD and SIRT) as well as for transmission through slab geometries.

PMID- 19396287
TI  - Non-invasive optical mapping of the piglet brain in real time.
AB  - We have performed non-invasive, real-time optical mapping of the piglet brain
      during a subcortical injection of autologous blood. The time resolution of the
      optical maps is 192 ms, thus allowing us to generate a real-time video of the
      growing subcortical hematoma. The increased absorption at the site of blood
      injection is accompanied by a decreased absorption at the contralateral brain
      side. This contralateral decrease in the optical absorption and the corresponding
      time traces of the cerebral hemoglobin parameters are consistent with a reduced
      cerebral blood flow caused by the increased intracranial pressure.

PMID- 19396288
TI  - Numerical modeling of thermal refraction inliquids in the transient regime.
AB  - We present the results of modeling of nanosecond pulse propagation in optically
      absorbing liquid media. Acoustic and electromagnetic wave equations must be
      solved simultaneously to model refractive index changes due to thermal expansion
      and/or electrostriction, which are highly transient phenomena on a nanosecond
      time scale. Although we consider situations with cylindrical symmetry and where
      the paraxial approximation is valid, this is still a computation-intensive
      problem, as beam propagation through optically thick media must be modeled. We
      compare the full solution of the acoustic wave equation with the approximation of
      instantaneous expansion (steady-state solution) and hence determine the regimes
      of validity of this approximation. We also find that the refractive index change
      obtained from the photo-acoustic equation overshoots its steady-state value once
      the ratio between the pulsewidth and the acoustic transit time exceeds a factor
      of unity.

PMID- 19396289
TI  - Microoptical and integrated optical fs/ps pulse shapers.
AB  - The generation of 875 fs nearly rect-shaped pulses from 96 fs sech 2 shaped
      Ti:sapphire laser pulses by means of a microoptical pulse shaper is presented
      conceptually and experimentally. Pulse shaping is performed by time frequency
      filtering of the input spectrum within a Fourier optical 4f setup with entrance
      and exit grating. The setup uses an optimized reflective filter concept with 40
      nm filter bandwidth giving improved pulse shape at acceptable temporal pulse
      extension. Moreover, an integrated optical concept with inherent dispersion
      compensation for shaping ps pulses is proposed which employs an integrated film
      waveguide based telescopic system with curved waveguide mirrors for improved
      filtering of a limited spectral bandwidth.

PMID- 19396290
TI  - Dynamics of self-focused femtosecond laser pulses in the near and far fields.
AB  - We investigate the propagation of femtosecond pulses in a nonlinear, dispersive
      medium at powers several times greater than the critical power for self focusing.
      The combined effects of diffraction, normal dispersion and cubic nonlinearity
      lead to pulse splitting. We show that detailed theoretical description of the
      linear propagation of the pulse from the exit face of the nonlinear medium (near
      field) to the measuring device (far field) is crucial for quantitative
      interpretation of experimental data.

PMID- 19396291
TI  - Control optimization of spherical modal liquid crystal lenses.
AB  - Liquid crystal modal lenses are switchable lenses with a continuous phase
      variation across the lens. A critical issue for such lenses is the minimization
      of phase aberrations. In this paper we present results of a simulation of control
      signals that have a range of harmonics. Experimental results using optimal
      sinusoidal and rectangular voltages are presented. A lack of uniqueness in the
      specification of the control voltage parameters is explained. The influence of a
      variable duty cycle of the control voltage on an adaptive lens is investigated.
      Finally we present experimental results showing a liquid crystal lens varying its
      focal length.

PMID- 19396292
TI  - Truncated Newton's optimization scheme for absorption and fluorescence optical
      tomography: Part I theory and formulation.
AB  - The development of non-invasive, biomedical optical imaging from time-dependent
      measurements of near-infrared (NIR) light propagation in tissues depends upon two
      crucial advances: (i) the instrumental tools to enable photon "time-of-flight"
      measurement within rapid and clinically realistic times, and (ii) the
      computational tools enabling the reconstruction of interior tissue optical
      property maps from exterior measurements of photon "time-of-flight" or photon
      migration. In this contribution, the image reconstruction algorithm is formulated
      as an optimization problem in which an interior map of tissue optical properties
      of absorption and fluorescence lifetime is reconstructed from synthetically
      generated exterior measurements of frequency-domain photon migration (FDPM). The
      inverse solution is accomplished using a truncated Newtons method with trust
      region to match synthetic fluorescence FDPM measurements with that predicted by
      the finite element prediction. The computational overhead and error associated
      with computing the gradient numerically is minimized upon using modified
      techniques of reverse automatic differentiation.

PMID- 19396293
TI  - Truncated Newton's optimization scheme for absorption and fluorescence optical
      tomography: Part II Reconstruction from synthetic measurements.
AB  - Using two dimensional synthetic frequency-domain measurements, the inverse
      imaging problem is solved for absorption and fluorescence lifetime mapping with
      the truncated Newtons optimization scheme developed in Part I of this
      contribution. Herein, we present reconstructed maps of absorption owing to a
      fluorophore from excitation and emission measurements which detail the presence
      of tissue heterogeneities characterized by tenfold increase in fluorescent
      contrast agent. Our results confirm that fluorescence provides superior mapping
      of heterogeneities over excitation measurements. Using emission measurements we
      then map fluorescent lifetime under conditions of tenfold uptake of contrast
      agent in tissue heterogeneities. The ability to map fluorescent quenching and
      lengthening of contrast agents facilitates the solution of the inverse problem
      and further improves the ability to reconstruct tissue heterogeneities.

PMID- 19396294
TI  - Experiments on long wavelength (1550 nm) "plug and play" quantum cryptography
      systems.
AB  - An interferometric quantum cryptographic system at 1550nm wavelength using gated
      InGaAs Avalanche Photo Diodes as single-photon receivers is demonstrated for a
      transmission distance up to 40 km.

PMID- 19396295
TI  - Three-dimensional field structure in open unstable resonators Part I: Passive
      cavity results.
AB  - The three-dimensional field distribution of the diffractive cavity mode structure
      in a passive, open, unstable resonator is presented as a function of the
      equivalent Fresnel number of the cavity. The qualitative structure of this
      intracavity field distribution, including the central intensity core (or
      oscillator filament), is characterized in terms of the Fresnel zone structure
      that is defined over the cavity feedback aperture. Previous related research is
      reviewed.

PMID- 19396296
TI  - Three-dimensional field structure in open unstable cavities Part II: Active
      cavity results.
AB  - The three-dimensional field distribution of the diffractive cavity mode structure
      in an active, open, unstable laser resonator is presented as a function of the
      equivalent Fresnel number of the cavity. The active cavity mode structures are
      compared to that of the corresponding passive cavity so that the effects of a
      spatially extended, homogeneously broadened, saturable gain medium on the cavity
      field structure may be ascertained. The qualitative structure of this intracavity
      field distribution, including the central intensity core (or oscillator
      filament), is explained in terms of the Fresnel zone structure defined over the
      cavity feedback aperture.

PMID- 19396297
TI  - Focal shift in vector beams.
AB  - We examine the three-dimensional intensity distribution of vector Bessel-Gauss
      beams with general polarization near the focus of a nonaperturing thin lens.
      Recently reported linearly and azimuthally polarized Bessel-Gauss beams are
      members of this family. We define the width and focal plane of such a vector beam
      using an encircled-energy criterion and calculate numerically that, as for scalar
      beams, the true focus occurs not at the geometric focus of the lens but rather
      somewhat closer to the lens. This focal shift depends on the mode number and
      system parameters and is largest for a narrow beam, long lens focal length, and
      large wavelength.

PMID- 19396298
TI  - Polarimetric images of a cone.
AB  - Scenes from a Mueller matrix movie of a brass cone are shown. From the Mueller
      matrix image, a variety of polarization measures are calculated and displayed.
      These polarization images reveal considerable details about the geometry of the
      cone despite the fact that the images are taken from a single vantage point, i.
      e. they are "flat images". As the cone rotates, the orientation of the
      diattenuation and retardance follow the shape of the cone, providing a clear
      indication of its shape.

PMID- 19396299
TI  - Introduction.
AB  - The role of optics in sensing is obviously expanding; witness the large number of
      papers presented at the Annual Meeting of the Optical Society of America held in
      October 1998. From sensing inside the human body to sensing in outer space, every
      Technical Group within OSA had papers that highlighted some of the new
      technologies being employed in sensors and some of the applications for sensing.
      A look at a few of the titles of some of the symposia serves to illustrate the
      breadth of sensing within the optics community: Optical Sensors for Combustion
      Diagnostics, Polymer and Molecular Systems for Optical Sensing,
      Multidiscriminant/Multispectral/Polarization Imaging, Novel Imaging Techniques in
      Biomedicine, Nonlinear and Novel Imaging Techniques. The papers in the sessions
      ranged from discussions of basic physics to presentations of highly engineered
      applications. I see this as one of the very useful roles that conferences can
      serve - the interchange of information between those who emphasize component
      development and those who develop system requirements.

PMID- 19396300
TI  - Extremely nonlinear photosensitive liquid crystals for image sensing and sensor
      protection.
AB  - Optically induced nematic liquid crystal axis reorientation results in
      extraordinarily large nonlinear refractive index changes that could find
      practical applications in conjunction with cw or long-pulse lasers. We discuss
      the origins of these nonlinearities, and present the results of recent
      experimental studies of image conversion, optical limiting and sensor protection
      using aligned dye-doped nematic liquid crystal films in all-optical
      configurations. These processes are characterized by unprecedented low threshold
      laser powers, thus presenting nonlinear photosensitive nematic liquid crystals as
      promising next generation image processing and optical switching/limiting
      material.

PMID- 19396301
TI  - Ruby films as surface temperature and pressure sensors.
AB  - Epitaxial films of chromium doped alumina, 0.3 microns in thickness, were grown
      on single crystal sapphire substrates for use as surface thermometers. Curve
      fitting was performed on the R1 and R2 fluorescence peaks, and the line widths
      and peak shifts were used to determine the temperature of the surface during
      sliding contact with a variety of plastic bearings. Temperatures could be
      determined with a repeatability of 2 degrees C, and adequate signal for
      temperature determination could be obtained in 30-100 msec. in dots that were 200
      microns in diameter, using a 0.25 watt argon laser. Both average (nominal) and
      local temperature increases were measured. Pressure-induced shifts could be
      treated as an error to the temperature determination.

PMID- 19396302
TI  - On probing molecular monolayers: a spectroscopic optical waveguide approach of
      ultra-sensitivity.
AB  - A broadband, multichannel, single-mode, planar waveguide based spectrometer was
      developed for probing molecular monolayers. A protein sub-monolayer (thickness h
      @ 3 nm, imaginary part of refractive index kl oe 0.01) immobilized on the
      waveguide surface was characterized by the waveguide attenuated total reflection
      (ATR) spectrometer. A sensitivity enhancement of 4 orders of magnitude, compared
      to conventional transmission measurements, has been experimentally achieved in
      the characterization of ultra-thin films. In addition, polarized spectroscopic
      measurements at the TE and TM waveguide modes were implemented to determine the
      average orientation angle of the adsorbed molecules. The work developed here is a
      new research tool for the investigation of some fundamental aspects of molecular
      films and a novel platform to develop new technological devices of high
      sensitivity and selectivity such as biosensors.

PMID- 19396303
TI  - Applications of long-period gratings to single and multi-parameter sensing.
AB  - Photoinduced long-period gratings are shown as versatile sensors for temperature,
      axial strain and index of refraction measurements. The principle of operation of
      such devices is discussed and the application to simultaneous temperature and
      strain is demonstrated.

PMID- 19396304
TI  - Extended depth of field and aberration control for inexpensive digital microscope
      systems.
AB  - We present a new application and current results for extending depth of field
      using wave front coding. A cubic phase plate is used to code wave fronts in
      microscopy resulting in extended depths of field and inexpensive chromatic
      aberration control. A review of the theory behind cubic phase plate extended
      depth of field systems is given along with the challenges that are face when
      applying the theory to microscopy. Current results from the new extended depth of
      field microscope systems are shown.

PMID- 19396305
TI  - Sensing lesions in tissues with light.
AB  - The use of light for probing and imaging of biomedical media offers the promise
      for development of safe, noninvasive, and inexpensive clinical imaging modalities
      with diagnostic ability. Various properties of light together with the ways it
      interacts with biological tissues may provide multiple windows to peer inside
      body organs. Principles and methods for extraction of information about body
      functions and lesions that capitalize on temporal, spectral, polarization, and
      spatial characteristics of transmitted light are briefly outlined. As
      illustrations of the potential and efficacy of light-based techniques, time
      sliced and spectroscopic images of normal and cancerous human breast tissues
      recorded with a femtosecond Ti:sapphire laser and a broadly tunable Cr:forsterite
      laser, respectively, are presented.

PMID- 19396306
TI  - Low-threshold laser oscillation due to group-velocity anomaly peculiar to two-
      and three-dimensional photonic crystals.
AB  - An analytical expression of the lasing threshold for arbi trary photonic crystals
      was derived, which showed their reduction due to small group velocities of
      electromagnetic eigenmodes. The lasing threshold was also evaluated numerically
      for a two-dimensional photonic crystal by examining the divergence of its
      transmission and reflection coeffcients numerically. A large reduction of lasing
      threshold caused by a group-velocity anomaly that is peculiar to two- and three-
      dimensional photonic crystals was found.

PMID- 19396307
TI  - High-power "Watt-level" CW operation of diode-pumped 2.7 aem fiber lasers using
      efficient cross-relaxation and energy transfer mechanisms.
AB  - We report the demonstration of high power (660 mW) CW operation of a diode-pumped
      mid-IR Er fiber laser. This was achieved by using efficient depopulation of the
      lower laser level via enhanced cross-relaxation between Er ions and energy
      transfer to Pr ions (at doping densities much higher than those used previously
      in Er:ZBLAN), along with optimal pumping of such lasers via custom-designed
      double-clad fluoride fibers.

PMID- 19396308
TI  - Ellipticity and pulse shape dependence of localised wavepackets.
AB  - Atoms in intense, high-frequency laser fields exhibit the remarkable property
      that they can be stable against ionization. We investigate the structure of
      stabilized wavepackets for a two-dimensional model hydrogen atom interacting with
      an intense, high frequency laser pulse as a function of the laser pulse
      ellipticity and laser pulse rise-time. The computed wavepackets are compared with
      the corresponding Kramers-Henneberger (K-H) ground states. Laser pulse turn-on
      effects are studied by contrasting the structure of the localized part of the
      wavepackets and the ionizing part of the wavepackets for three different
      ellipticities and for various pulse turn-on times.

PMID- 19396309
TI  - Spontaneous emission lifetime of carriers in a semiconductor microcavity measured
      by photoluminescence without distortion by reabsorption.
AB  - A theory for carrier decay rates and a technique for measuring them are reported.
      Modification of the spontaneous emission rate of carriers by a semiconductor
      microcavity is investigated with 100-nm-thick bulk GaAs. Reabsorption makes the
      cavity-mode photoluminescence (PL) decay much faster than the square of the
      carrier density. Here reabsorption distortion is avoided by collecting PL that
      escapes the microcavity directly without multiple reflections: a ZnSe prism glued
      to the top mirror allows PL to escape at angles beyond the cutoff angle for total
      internal reflection without the prism. At these steep angles, the stop band of
      the top mirror has shifted to higher energy, so that it does not impede PL
      emission. Removal of most of the bottom mirror decreases the true carrier decay
      rate by only 25%, showing that the large enhancements deduced from cavity-mode PL
      are incorrect. Fully quantum mechanical computation including guided modes
      corroborates this conclusion. The prism technique could be used to study carrier
      dynamics and competition between guided and cavity modes in microcavities below
      and near threshold.

PMID- 19396312
TI  - [When to use steroid treatment for those patients with drug-induced acute
      interstitial nephritis?].

PMID- 19396313
TI  - [Icodextrin as first treatment: reasons to be optimistic].

PMID- 19396314
TI  - [The role of calcium, calcitriol and their receptors in parathyroid regulation].
AB  - The mechanism of regulation of Parathyroid hormone (PTH) is complex, and diverse
      factors are involved: the fundamental ones are calcium, calcitriol and
      phosphorus. Calcium and calcitriol's mechanism of action takes place through its
      specific receptors, the calcium-sensing receptor (CaR) and the Vitamin D Receptor
      (VDR). These two factors have an effect not only on its specific receptors, but
      also they can modify the other receptor in a positive manner, promoting its
      actions and demonstrating a cooperative effect between the two. Along with
      calcium and calcitriol, drugs used in the treatment of Chronic Kidney Disease
      Mineral Bone Disorders (CKD-MBD) also act directly or indirectly on CaR and VDR
      and therefore are also responsible for the regulation of the parathyroid gland.

PMID- 19396315
TI  - [Nephrogenic fibrosing dermopathy or nephrogenic systemic fibrosis? What do we
      know and what do we have to learn?].
AB  - Nephrogenic systemic fibrosis (NSF) was first recognized as a unique entity in
      1997 and subsequently defined in the literature in 2000 as a novel fibrosing
      disorder occurring in the setting of renal disease. Prevention, early recognition
      and treatment are essential to limiting its impact. The most important risk
      factors for developing NSF are chronic or significant acute kidney disease
      (especially dialysis dependent patients) and the administration of gadolinium
      (GD3) containing contrast agents, agents that cause NSF by releasing free
      gadolinium (GD3) into tissues based on their pharmacokinetics. International
      commissions in drug control and medicinal products recommend to avoid gadolinium
      based contrast agents in patients with GFR < 30 ml/minute/1.73 m(2).
      Unfortunately there is lack of universally effective therapy at this time and the
      literature is based on case reports and small case series. Recommendations to
      guide the use of gadolinium based contrast agents in patients with underlying
      kidney disease should be individualized and considered in consultation with the
      ordering physician, radiologist and nephrologist.

PMID- 19396316
TI  - [Institute for clinical management of nephro-urological diseases: the benefits of
      a quality care programme].
AB  - The Clinic Institute of Nefro and Urology (ICNU) was formed in Clinic Hospital of
      Barcelona in 1999. It grouped together services of Nephrology, Urology and Renal
      Transplant. At the same time, in order to ensure Quality in this process of
      change, we designed a specific quality program. In this program, we defined
      objectives to improve the quality of these services in one year and we defined
      different quality indicators in order to maintain and monitor health quality. The
      indicators referred to technical quality and perceived quality and we
      periodically evaluated their evolution. The results of the last five years
      indicate that the majority of the indicators have improved, except those
      concerning infections surgery and the response to complaints. This has helped the
      consolidation and recognition of the work of this innovatory project in the
      health management of the nephrologic and urinary systems that locate the patient
      in the center of the organization and recognize the health professionals as the
      true managers of this model.

PMID- 19396317
TI  - [Clinical and economic repercussions of the use of tunneled haemodialysis
      catheters in a health area].
AB  - INTRODUCTION: Tunneled catheters in hemodialysis are associated with poor
      prognosis, however, few prospective studies have been designed to specifically
      evaluate this aspect. The objective has been evaluate the impact of tunneled
      catheter in patient mortality and costs attributable to this procedure. METHODS:
      A seven years prospective cohort study was performed in all patients starting
      hemodialysis in our health care area adjusting for comorbidity and albumin. The
      study comprised 260 patients with Charlson index 7.05 +/- 2.8 (age 65.5 years,
      62.3% males, 25% with diabetes mellitus and 37.7% with a previous cardiovascular
      event. RESULTS: The first vascular access was a catheter in 47.3%, PTFE in 11.2%
      and native arteriovenous fistula in 41.5%. Minimum follow-up was one year, with
      an average of 2.31 years/patient. The mortality risk adjusted for comorbidity was
      greater among the patients that started with catheterization, HR: 1.86 [1.11
      3.05]. This negative effect was observed in 57.30% of those subjected to
      catheterization at any stage (HR: 1.68 [1.00-2.84] and proved to be time
      dependent, i.e., the longer catheterization, the greater the risk: HR: 7.66 [3.34
      17.54] third versus first tertil. The cost directly attributable to catheter use
      was 563.31 euros/month. All poor prognosis groups showed lower albumin and
      hemoglobin levels, without differences in efficacy. CONCLUSION: Tunneled catheter
      use at any time is associated with an increased risk of death. This effect
      increases with the duration of catheterization, both circumstances are
      independent of patient comorbidity at time start of hemodialysis and implies a
      higher net cost.

PMID- 19396318
TI  - [Effect of using icodextrin as a starting therapy for peritoneal permeability].
AB  - Peritoneal permeability differs between patients at the time of starting
      peritoneal dialysis (PD) and it can increase along with time on the technique.
      This fact is related to peritonitis, the biocompatibility of the dialysis fluids
      and the use of glucose as osmotic agent. The aim of the present study was to
      evaluate if the use of one exchange a day of icodextrine from the time of DP
      initiation affects the evolution of peritoneal permeability. PATIENTS AND
      METHODS: 56 patients starting PD (mean age: 48.3 +/- 14.0; 62.5% males; 17.9%
      diabetics) that used one exchange a day with icodextrine from the time of
      starting PD. We performed a peritoneal transport kinetic study at the time of
      starting PD and then every 6 months during two years. We calculated the
      peritoneal mass transfer area coefficient of creatinine (Cr-MTAC) and urea (U
      MTAC) as well as the D/P creatinine relationship (D/P Cr). As a control group we
      used the results of Cr-MTC of 249 patients that had used glucose as the only
      osmotic agent from the time of starting PD. RESULTS: The peritoneal transport,
      calculated using Cr-MTC, U-MTC and D/P Cr, diminished at 12 months (11.7+/-5.7
      vs. 8.1+/-3.1; 23.5+/-7.3 vs. 18.9+/-3.8; 0.72+/-0.09 vs. 0.67+/-0.08;
      respectively), staying stable afterwards.We found that high transporters (HA)
      patients (higher quatril Cr-MTC ) showed a higher diminution of Cr-MTAC along the
      first year of treatment. The diminution of Cr-MTAC after 12 months using
      icodextrine was significantly higher (p<0.001) that the one observed in the
      control group that only used glucose as osmotic agent (10.5+/-5.3 vs. 10.1+/
      4.6). We found that high transporters (HA) patients (higher quatril Cr-MTC)
      showed a higher decrease of Cr-MTAC along the first year of treatment.
      CONCLUSION: the use of icodextrine at the time of starting PD might help to
      correct the high transport status observed in some patients during the first
      months of treatment. The peritoneal transport kinetic studies performed at 6 and
      12 months after starting PD are more representative of the long term peritoneal
      transport characteristics of the patients than those performed at the time of
      starting PD.

PMID- 19396320
TI  - [Changes in the pre-transplant bone-mineral metabolism do not affect the initial
      progress of the renal graft].
AB  - BACKGROUND: Abnormalities in serum calcium, phosphate, and Parathyroid Hormone
      (PTH) concentrations are common in patients with chronic kidney disease and have
      been associated with increased morbidity and mortality. One of the most common
      problems in the first weeks after renal transplantation is Delayed Graft Function
      (DGF). There are several well-known risk factors for DGF development, but the
      role of calcium phosphate-PTH homeostasis as a risk factor for early graft
      dysfunction is controversial. This issue was addressed in the current study.
      METHODS: Pretransplant PTH, calcium and phosphate values were gathered in 449
      patients that received a renal transplant in our center between 1994 and 2007.
      Other variables expected to influence the risk for delayed graft function were
      included from the clinical charts. RESULTS: The incidence of DGF was 27.3%. DGF
      development was significantly associated with recipient age, type and need of
      renal replacement therapy, peak panel reactive antibodies, transfusion number and
      donor age. There were no significant differences in the mean pretransplant values
      of calcium (9.4 +/- 1.0 vs. 9.5 +/- 0.9 mg/dl, p = 0.667), phosphate (5.7 +/- 1.8
      vs. 5.5 +/- 1.5 mg/dl, p = 0.457), calcium-phosphate product (53.5 +/- 17.2 vs.
      51.8 +/- 14.6 mg(2)/dl(2), p = 0.413) and PTH (315 +/- 312 vs. 340 +/- 350 pg/ml,
      p = 0.530) between patients with and without DGF. CONCLUSIONS: In our study
      population pretransplant serum PTH, calcium and phosphorus levels have no
      influence on the risk for DGF.

PMID- 19396319
TI  - [Changing the frequency of administration of darbepoetin alfa (from weekly to
      fortnightly) maintains the haemoglobin levels in patients undergoing peritoneal
      dialysis].
AB  - SUMMARY BACKGROUND: Less frequent dosing regimens during anemia treatment could
      benefit Peritoneal Dialysis (PD) patients. We investigated the effectiveness of
      darbepoetin alfa dosed every-other-week (Q2W) for maintaining hemoglobin (Hb)
      levels (11-13 g/dL). PATIENTS AND METHODS: One hundred and nine PD patients from
      14 centers participated in an 8-month observational, prospective study. Patients
      (Hb 11-13 g/dL) receiving weekly (QW) darbepoetin alfa switched to Q2W dosing at
      the investigator's discretion. Doses were adjusted according to published
      guidelines. RESULTS: Sixty-nine percent (75 out of 109) of patients switched to
      Q2W dosing. Thirty-three percent maintained the g/week, equivalent to twice the
      previous mean weekly dose (26.1-25.8 g/week, QW dose). Forty-seven percent
      received a dose reduction (35.8-20.2 equivalent to the previous QW dose). More
      patients in the maintenance dose group 11 g/dL than those receiving a reduced
      weekly dose (80% vs. had Hb levels 51.4%, respectively, p = 0.0236). During the
      Q2W phase, the mean Hb level ranged from 12.0-12.5 g/dL for the maintenance dose
      group and 11.5-12.0 g/dL for the reduced dose group. From the switch to the end
      of the study, the mean (SD) change in Hb was -0.7 g/dL (0.98 g/dL, p = 0.0557)
      and -0.6 g/dL (1.6 g/dL, p = 0.1296) for the maintenance and reduced dose groups,
      respectively. The Q2W darbepoetin alfa was well tolerated. Only a single
      treatment-related adverse event (polycythemia) occurred. CONCLUSION: The majority
      of PD patients receiving QW darbepoetin alfa can be effectively switched to Q2W
      and still maintain their Hb level.

PMID- 19396321
TI  - [Use of MDRD equation to detect occult renal failure and reduce the risk of
      digitalis overdose].
AB  - INTRODUCTION: Digoxin overdose is closely related to Chronic Kidney Disease and
      creatinine dosage adjustment is usually needed. Our goal was to assess the
      advantages of serum creatinine and the MDRD equation to detect hidden renal
      insufficiency to reduce the overdose Digital risk. METHODS: We describe all
      digoxin samples processed and registered in our hospital laboratory database for
      a year. Patients under 18 years and samples below therapeutic ranges were
      excluded. Chi square (p<0.05), ROC curves and logistic regression analysis were
      conducted. SPSS software was used. RESULTS: Between 1228 digoxin samples taken to
      679 patients (273 men, 77 +/- 10 years old , and 406 women 82 +/- 8 years old),
      14% were over therapeutic range (28 men and 67 women). Significant differences
      were observed in over dosage between high creatinine group regarding to normal
      creatinine group (31% vs. 10% in men, 44% vs. 15% in women). ROC curves showed
      that the most accurate levels to predict digoxin over dosage were MDRD<56
      ml/min/1.73 m(2) in men and MDRD<52 ml/min/1.73 m(2) in women. 68% of over dosage
      men had declines of MDRD levels, compared to 61% with high creatinine levels, 81%
      of over dosage women had declines of MDRD compared to 51% with elevated
      creatinine levels. CONCLUSIONS: Even in patients with normal creatinine levels,
      chronic kidney disease enhances digoxin over dose risk. Using the decline of
      glomerular filtration rate estimated by the MDRD equation is better than elevated
      creatinine levels to detect digoxin overdose, thus constituting a very useful
      tool to reduce the risk of overdose, especially among women.

PMID- 19396322
TI  - [Acetate-free on-line PHF: how to improve hyperacetatemia and haemodynamic
      tolerance].
AB  - SUMMARY BACKGROUND: The small quantity of acetate present in the dialysis fluid
      exposes patient's blood to an acetate concentration 30-40 times the physiological
      levels. This amount is even greater in hemodiafiltration on-line. Our purpose was
      to evaluate the clinical-analytical effects using three different dialysis
      techniques in the same patient. METHODS: 35 patients on hemodialysis were
      included. All patients were treated with conventional bicarbonate dialysate for 3
      months, after randomization were switched to first be treated with PHF online
      with standard bicarbonate dialysate for 6 months and then switched to PHF on-line
      acetate-free dialysate for the other 6 months or to invert the two last periods.
      Blood samples were drawn monthly throughout the study and clinical data were
      obtained. RESULTS: Postdialysis blood acetate levels were higher in patients
      treated with conventional bicarbonate dialysate with respect to the period of PHF
      with free-acetate dialysate. Moreover, the percentage of patients with
      postdialysis blood acetate levels in the pathologic range was higher in patients
      treated with conventional bicarbonate dialysate respect to PHF on-line acetate
      free dialysate period (61% vs. 30%). Serum concentrations of chloride
      postdialysis were higher and serum concentrations of bicarbonate pre and
      posthemodialysis were lower in the PHF free-acetate period. The incidence of
      hypotensive episodes was significantly lower in the PHF on-line with conventional
      dialysate. CONCLUSIONS: PHF on-line with free-acetate dialysate allows that most
      of patients finished hemodialysis with blood acetate levels in the physiologic
      ranges. PHF on-line is a predilutional hemodiafiltration treatment with better
      tolerance than hemodialysis with standard bicarbonate dialysate.

PMID- 19396323
TI  - [Proteinuria in urinary infection and acute pyelonephritis in paediatric
      patients: can it replace scintigraphic studies in diagnostic localisation?].
AB  - ANTECEDENTS AND OBJECTIVES: The location of the urinary tract infection in
      children has serious implications both in therapy and prognosis. Affectation in
      gammagraphic studies is considered the "gold standard" for the diagnosis of acute
      pyelonephritis. Several studies with biomarkers have been made with controverted
      results. The objective of this study is to set the utility of beta2
      microglobuline, alfa1-microglobuline, Cistatine C, IgG and albumin in the
      location of the infection, through the analysis of the relation among their
      urinary excretion, clinical and laboratory parameters and the renal scintigraphy
      findings. PATIENTS AND METHODS: Prospective observational study made in 40
      patients, aged from 1 month to 11 years, after their Hospital admission with
      suspicion for acute pyelonephritis. Exclusion criteria were: decrease in the
      glomerular filtration rate, malnutrition, massive albuminuria and history or
      findings of nephrourologic disease. Clinical and laboratory variables were
      analyzed, and renal ultrasonography and scintigraphy were performed within the
      first seven days after admission. Once the fever dropped, the urinary creatinine
      protein ratio was analyzed. After the acute process, a renal scintigraphy was
      performed in order to detect renal scars. The non-parametric Mann-Whitney U test
      has been used as the statistical hypothesis test, and Chi-square and Fisher s
      exact tests have been used to compare the qualitative variables. RESULTS: The
      glomerular filtration rate, as well as the ultrasonography scan, was normal in
      all patients. 45% of the children (24/80 kidneys) had scintigraphic alterations
      that were compatible with acute pyelonephritis, and there were not differences in
      proteinuria between these and those with normal scintigraphy. To greater age
      greater probability of scintigraphic affectation. The sensitivity and specificity
      of leukocytes and CRP to predict pyelonephritis were 77-65% and 94-52%, r = 0.70
      (CI 95% 0.54-0.87) y 0.75 (CI 95% 0.60-0.90) respectively. An apparent relation
      between the maximum temperature or duration of the symptoms and the renal
      affectation does not exist. In all the children, the normality of urinary markers
      of renal function was confirmed once the acute phase had passed, even in those 3
      patients with renal scars (7.5%). CONCLUSIONS: Renal scintigraphy is still being
      the reference pattern for the diagnosis of acute pyelonephritis in Pediatrics.
      The combined use of different urinary markers of renal function does not increase
      its sensitivity. It is necessary to do research in order to confirm the utility
      of new biomarkers.

PMID- 19396325
TI  - [Research and projects: some clarification].

PMID- 19396324
TI  - [Tuberculous peritonitis in peritoneal dialysis].
AB  - We report a patient in Automatic Peritoneal Dialysis (APD) with tuberculous
      peritonitis by possible peritoneal infection due to the proximity between
      fallopian tube and the left ovary, a peritoneal liquid culture was constantly
      negative. The patient presented a bad clinic evolution. Her only medical history
      was hypercalcemia six months before developing a peritonitis and occasionally
      nausea and vomits To confirm the diagnosis it was needed a peritoneal biopsy by
      means of a laparoscopy with a removal of the peritoneal catheter and left
      anexectomy. Now, the patient is asintomatic in daily home hemodialysis.

PMID- 19396326
TI  - [A paper on independent clinical research in Spain].

PMID- 19396327
TI  - [Membranoproliferative glomerulonephritis and monoclonal gammopathy of uncertain
      significance].

PMID- 19396328
TI  - [Infection in haemodialysis catheters: a retrospective examination].

PMID- 19396329
TI  - [The importance of starting regular haemodialysis through a native arteriovenous
      venous fistula].

PMID- 19396330
TI  - [The current situation for vascular access in the province of Caceres].

PMID- 19396331
TI  - [Disease by CMV resistant to Ganciclovir. Should plasma valganciclovir levels be
      monitored in high risk patients?].

PMID- 19396332
TI  - [Ileal intussusception by carcinoid tumour in a patient with chronic renal
      failure].

PMID- 19396333
TI  - [Cefepime-induced encephalopathy in patients with renal failure].

PMID- 19396334
TI  - [Haemodialysis management for salicylate intoxication].

PMID- 19396335
TI  - [Candida-induced recurrent peritonitis after peritoneal catheter reinsertion].

PMID- 19396336
TI  - [Pneumaturia and kidney polycystosis in adults].

PMID- 19396337
TI  - Bis-tridentate Chelates of an Asymmetric Ligand: X-ray Structures and Solution
      NMR Characterization of Divalent Zinc Triad Metal Ion Complexes of N-(2
      pyridylmethyl)-N-(2-(methylthio)ethyl)amine.
AB  - Divalent zinc triad metal ion complexes of type M(L)(2)(ClO(4))(2) (L = N-(2
      pyridylmethyl)-N-(2-(methylthio)ethyl)amine) with N(4)S(2) metal coordination
      spheres were isolated and characterized by X-ray crystallography and variable
      temperature proton NMR. Although bis-tridentate chelates have nine geometric
      isomers, the crystallographically characterized complexes of all three metal ions
      had trans facial octahedral coordination geometry with C(i) symmetry. Despite the
      low coordination number and geometric preferences of d(10) metal ions, which
      facilitate inter- and intramolecular exchange processes, dilute solutions of
      these bis-tridentate chelates exhibited slow geometric isomerization. Symmetry,
      sterics and shielding arguments supported specific isomeric assignments for the
      major and minor chemical shift environments observed at low temperature. At
      elevated temperature, rapid intramolecular exchange occurred for all three
      complexes but slow intermolecular exchange on the coupling constant time scale
      was evidenced through detection of J(HgH) interactions for Hg(L)(2) (2+). These
      unusual observations are discussed in the context of the zinc triad metal ion
      coordination chemistry of related bis-tridentate chelates.

PMID- 19396338
TI  - The use of amnion-derived cellular cytokine solution (ACCS) in accelerating
      closure of interstices in explanted meshed human skin grafts.
AB  - Meshed, split-thickness skin grafts, especially when required to be widely
      spread, do not obtain immediate biologic closure. In patients with burns that
      cover a large percentage of the body surface area, this leaves the patient at
      risk for metabolic problems and life-threatening infection. OBJECTIVE: The
      purpose of this study was to determine whether amnion-derived cellular cytokine
      solution could improve epithelialization kinetics and accelerate closure of
      meshed skin graft interstices. METHODS: Human meshed, split-thickness skin grafts
      were explanted to athymic "nude" rats and treated with 3 different regimens of
      amnion-derived cellular cytokine solution (groups I, II, and III) or normal
      saline (group IV) as a control. Serial wound tracings of unepithelialized
      interstitial wound areas were compared over time. Two different preparations of
      amnion-derived cellular cytokine solution were also compared with one another,
      one containing animal components and the other free of animal components.
      RESULTS: Only 67.03% of interstices in control animals closed by day 9. This
      compared with 92.2% closure for group I, 83.72% for group II, and 90.64% for
      group III. Interstices in all 3 groups treated with amnion-derived cellular
      cytokine solution (with or without animal-derived components) closed faster
      statistically than in the control animals (P < .05). There were no statistical
      differences among the 3 amnion-derived cellular cytokine solution-treated groups.
      CONCLUSIONS: These data suggest that epithelialization kinetics and interstitial
      closure of meshed skin grafts can be accelerated with the use of amnion-derived
      cellular cytokine solution, a physiologic cocktail of cytokines, and provide
      support for a future clinical trial.

PMID- 19396339
TI  - Clinical perspectives on lacosamide.
AB  - Despite the advent of new antiepileptic drugs (AEDs) over the past 15 years, the
      treatment of uncontrolled partial-onset seizures remains a dilemma for
      clinicians. The most recent AEDs offer new mechanisms of action and more
      favorable safety profiles than the first generation of AEDs. Lacosamide (LCM) is
      the latest AED awaiting approval by the FDA for adjunctive use in partial-onset
      seizures. It differs from all other approved AEDs in that it has two novel
      mechanisms of action and favorable pharmacokinetic and safety profiles. The
      purposes of this article are to present the significant parameters for its use in
      clinical practice, by summarizing the preliminary results of phase II and III
      clinical trials, and to compare its efficacy data with other second-generation
      AEDs.

PMID- 19396340
TI  - Juvenile myoclonic epilepsy: more trials are needed to guide therapy.

PMID- 19396341
TI  - Patients with seizure clusters--identification of a high-risk group.

PMID- 19396342
TI  - Children with epilepsy: why can't they pay attention?

PMID- 19396343
TI  - Some long awaited answers regarding seizures during pregnancy.

PMID- 19396344
TI  - Molecular pathology of genetic epilepsies associated with GABAA receptor subunit
      mutations.
AB  - Mutations in ligand-gated ion channel genes associated with idiopathic
      generalized epilepsies have been reported in excitatory acetylcholine receptor
      alpha4 and beta2 subunit genes linked to autosomal dominant nocturnal frontal
      lobe epilepsy and in inhibitory GABA(A) receptor alpha1, beta3, gamma2, and delta
      subunit genes associated with childhood absence epilepsy, juvenile myoclonic
      epilepsy, pure febrile seizures, generalized epilepsy with febrile seizures plus,
      and generalized epilepsy with tonic-clonic seizures. Recent studies suggest that
      these mutations alter receptor function or biogenesis, including impaired
      receptor subunit messenger RNA stability, receptor subunit protein folding and
      stability, receptor assembly, and receptor trafficking.

PMID- 19396345
TI  - Making generalizations about seizure propagation.

PMID- 19396346
TI  - Novel therapeutic strategies for epilepsy--releasing the gene Genie.

PMID- 19396347
TI  - To depolarize or hyperpolarize? at the axon initial segment, EGABA sets the
      stage.

PMID- 19396348
TI  - Growth and reproductive patterns of Undaria pinnatifida sporophytes in a
      cultivation farm in Busan, Korea.
AB  - Monthly growth and reproduction of Undaria pinnatifida sporophytes were examined
      over a period of 5 months in a cultivation farm in Korea. A total of 11
      characters of Undaria were measured to determine a reliable morphological
      character representing its growth and reproduction. Plant weight of Undaria
      sporophytes increased steadily over the experimental period, but it increased in
      four different ways. Undaria pinnatifida increased body weight by growth in
      length and width (October-early December), and by growth in width with the
      thickening of blade and stipe when sporophytes began to be fertile (December
      January). In the middle of January, growth in length and width had almost stopped
      with the maturation of Undaria sporophytes. Finally, the weight of Undaria
      increased again by growth in width at the end of February. Present results
      indicate that Undaria sporophytes increase body weight by growth in length and
      width at different times, and the relationship between reproduction and
      vegetative growth is exclusive. Plant weight was positively correlated and fitted
      well with stipe width and blade width. The blade of Undaria was very thin (ca.
      254 mum) and breakable by wave action, but its stipe was strong and relatively
      thick (ca. 8.7 mm). Furthermore, the fertility of U. pinnatifida was fitted
      better with stipe width than blade width. Thus, we suggest that the stipe width
      is the most feasible character with which to estimate the growth and reproduction
      of U. pinnatifida sporophytes in the cultivation farm.

PMID- 19396349
TI  - An improved method for estimating R-phycoerythrin and R-phycocyanin contents from
      crude aqueous extracts of Porphyra (Bangiales, Rhodophyta).
AB  - One frequently-cited method for determining phycoerythrin (PE) and phycocyanin
      (PC) contents from crude aqueous extracts of red seaweeds utilizes peaks and
      troughs of absorbance spectra. The trough absorbance values are used to establish
      a linear or logarithmic baseline attributable to background scatter of
      particulate cellular debris not removed by centrifugation. Pigment contents are
      calculated by subtracting baseline values from PE and PC absorbance peaks. The
      baseline correction is intended to make the method independent of centrifugation
      time and/or speed. However, when crude extracts of Porphyra were analyzed using
      this protocol, R-PE and R-PC estimates were significantly affected by
      centrifugation time, suggesting that the method was not reliable for the genus.
      The present study has shown that with sufficient centrifugation, background
      scatter in Porphyra extracts can be removed, the remaining spectrum representing
      the overlapping absorbance peaks of water-soluble pigments in the extract. Using
      fourth derivative analysis of Porphyra extract absorbance spectra, peaks
      corresponding to chlorophyll, R-PE, R-PC, and allophycocyanin (APC) were
      identified. Dilute solutions of purified R-PE, R-PC and chlorophyll were scanned
      separately to identify spectral overlaps and develop new equations for phycobilin
      quantification. The new equations were used to estimate R-PE and R-PC contents of
      Porphyra extracts and purified R-PE, R-PC and chlorophyll solutions were mixed
      according to concentrations corresponding to the sample estimates. Absorbances
      and fourth derivative spectra of the sample extract and purified pigment mixtures
      were compared and found to coincide. The newly derived equations are more
      accurate for determining R-PE and R-PC of Porphyra than previously published
      methods.

PMID- 19396350
TI  - Allelopathic effects of Ulva pertusa, Corallina pilulifera and Sargassum
      thunbergii on the growth of the dinoflagellates Heterosigma akashiwo and
      Alexandrium tamarense.
AB  - The allelopathic effects of fresh tissue, dry powder and aqueous extracts of
      three macroalgae, Ulva pertusa, Corallina pilulifera and Sargassum thunbergii, on
      the growth of the dinoflagellates Heterosigma akashiwo and Alexandrium tamarense
      were evaluated using coexistence culture systems in which concentrations of the
      three macroalga were varied. The results of the coexistence assay showed that the
      growth of the two microalgae was strongly inhibited by using fresh tissue, dry
      powder and aqueous extracts of the three macroalga; the allelochemicals were
      lethal to H. akashiwo at relatively higher concentrations of the three macroalga.
      The macroalgae showing the most allelopathic effect on H. akashiwo and A.
      tamarense using fresh tissue were U. pertusa and S. thunbergii, using dry powder
      were S. thunbergii and U. pertusa, and using aqueous extracts were U. pertusa and
      C. pilulifera. We also examined the potential allelopathic effect on the two
      microalgae of culture filtrate of the three macroalga; culture medium filtrate
      initially exhibited no inhibitory effects when first added but inhibitory effects
      became apparent under semi-continuous addition, which suggested that continuous
      release of small quantities of rapidly degradable allelochemicals from the fresh
      macroalgal tissue were essential to effectively inhibit the growth of the two
      microalgae.

PMID- 19396351
TI  - Growth of Synechococcus sp. immobilized in chitosan with different times of
      contact with NaOH.
AB  - The thickness of the walls of the capsules of chitosan-immobilized Synechococcus
      cultures was dependent on the time of contact with NaOH and was directly related
      to culture growth. After an initial lag phase, probably caused by cell damage,
      the capsules obtained after 80 s in a 0.1 N NaOH solution showed better growth
      than that of free cell cultures (6.9 and 5.2 divisions in 10 days, respectively).

PMID- 19396352
TI  - Trait evaluation and trial cultivation of Dongfang No. 2, the hybrid of a male
      gametophyte clone of Laminaria longissima (Laminariales, Phaeophyta) and a female
      one of L. japonica.
AB  - Direct cultivation of the first filial generation of gametophyte clones from
      different Laminaria species is a highly effective way of utilizing kelp
      heterozygous vigor (heterosis). A male gametophyte clone of L. longissima Miyabe
      and a female one of L. japonica Areschoug were hybridized, generating Dongfang
      No. 2 hybrid kelp. This hybrid kelp was used directly in trial cultivation, and
      its agronomical traits were evaluated. L. longissima and L. japonica are
      obviously different and complement each other in their morphological
      characteristics and ecological performances. The hybrid of their gametophyte
      clones, Dongfang No. 2, showed 56.8% heterozygous vigor in yield. It also showed
      increased yields of 41.0 and 76.4% compared to the widely used commercial kelps
      Variety 1 and Variety 2, respectively. In large-scale cultivation trials at
      different locations and in different years, Dongfang No. 2 attained significantly
      higher yields than Varieties 1 and 2, increasing yield by 26.4% on average over
      Variety 1 and by 65.0% over the other. Dongfang No. 2 has a robust holdfast and a
      wide, long and deep-brown uniform blade, which shows a distinct middle groove. In
      addition to yield, Dongfang No. 2 also demonstrates obvious heterozygous vigor in
      other agronomic traits. It is resistant to strong irradiance, as the two
      commercial varieties are, has an appropriate vegetative maturation time, and
      adapts well to a range of different culture conditions. The parentage analysis
      using AFLP of total DNA and SNP of the ITS region of ribosomal RNA transcription
      unit showed that Dongfang No. 2 is the real hybrid of L. japonica and L.
      longissima.

PMID- 19396353
TI  - Antioxidant activities of sulfated polysaccharides from brown and red seaweeds.
AB  - The in vitro antioxidant activities of the following six sulfated polysaccharides
      were investigated: iota, kappa and lambda carrageenans, which are widely used in
      the food industry, fucoidan (homofucan) from the edible seaweed Fucus vesiculosus
      and fucans (heterofucans) F0.5 and F1.1 from the seaweed Padina gymnospora. With
      respect to the inhibition of superoxide radical formation, fucoidan had an IC(50)
      (the half maximal inhibitory concentration) of 0.058 mg.mL(-1), while the IC(50)
      for the kappa, iota and lambda carrageenans were 0.112, 0.332 and 0.046 mg.mL(
      1), respectively. All of the samples had an inhibitory effect on the formation of
      hydroxyl radicals. The results of peroxidation tests showed that fucoidan had an
      IC(50) of 1.250 mg.mL(-1) and that the kappa, iota and lambda carrageenans had an
      IC(50) of 2.753 and 2.338 and 0.323 mg.mL(-1), respectively. Fucan fractions
      showed low antioxidant activity relative to fucoidan. These results clearly
      indicate the beneficial effect of algal polysaccharides as antioxidants.

PMID- 19396354
TI  - On-line estimation of O(2) production, CO(2) uptake, and growth kinetics of
      microalgal cultures in a gas-tight photobioreactor.
AB  - Growth of the green algae Chlamydomonas reinhardtii and Chlorella sp. in batch
      cultures was investigated in a novel gas-tight photobioreactor, in which CO(2),
      H(2), and N(2) were titrated into the gas phase to control medium pH, dissolved
      oxygen partial pressure, and headspace pressure, respectively. The exit gas from
      the reactor was circulated through a loop of tubing and re-introduced into the
      culture. CO(2) uptake was estimated from the addition of CO(2) as acidic titrant
      and O(2) evolution was estimated from titration by H(2), which was used to reduce
      O(2) over a Pd catalyst. The photosynthetic quotient, PQ, was estimated as the
      ratio between O(2) evolution and CO(2) up-take rates. NH(4) (+), NO(2) (-), or
      NO(3) (-) was the final cell density limiting nutrient. Cultures of both algae
      were, in general, characterised by a nitrogen sufficient growth phase followed by
      a nitrogen depleted phase in which starch was the major product. The estimated PQ
      values were dependent on the level of oxidation of the nitrogen source. The PQ
      was 1 with NH(4) (+) as the nitrogen source and 1.3 when NO(3) (-) was the
      nitrogen source. In cultures grown on all nitrogen sources, the PQ value
      approached 1 when the nitrogen source was depleted and starch synthesis became
      dominant, to further increase towards 1.3 over a period of 3-4 days. This latter
      increase in PQ, which was indicative of production of reduced compounds like
      lipids, correlated with a simultaneous increase in the degree of reduction of the
      biomass. When using the titrations of CO(2) and H(2) into the reactor headspace
      to estimate the up-take of CO(2), the production of O(2), and the PQ, the rate of
      biomass production could be followed, the stoichiometrical composition of the
      produced algal biomass could be estimated, and different growth phases could be
      identified.

PMID- 19396355
TI  - Microalgal growth enhancement by levoglucosan isolated from the green seaweed
      Monostroma nitidum.
AB  - Microalgal growth was enhanced by the addition of levoglucosan to the culture
      medium. The growth-enhancing compound levoglucosan was isolated from the green
      seaweed Monostroma nitidum using water extraction, molecular fractionation, DEAE
      cellulose column chromatography, and high-performance liquid chromatography.
      Yield of the compound from seaweed powder was 5 x 10(-3)% (w/w). At 10 mM
      concentration, levoglucosan enhanced cell growth and the specific growth rate of
      all feed microalgal species tested (Chaetoceros gracilis, Chlorella ellipsoidea,
      Dunaliella salina, Isochrysis galbana, Nannochloris oculata, Navicula incerta,
      Pavlova lutheri, Tetraselmis suecica) in most culture media by approximately
      150%. Cellular fatty acid profiles and cell size differed marginally between
      cultures with and without levoglucosan.

PMID- 19396356
TI  - Phototrophic biofilms and their potential applications.
AB  - Phototrophic biofilms occur on surfaces exposed to light in a range of
      terrestrial and aquatic environments. Oxygenic phototrophs like diatoms, green
      algae, and cyanobacteria are the major primary producers that generate energy and
      reduce carbon dioxide, providing the system with organic substrates and oxygen.
      Photosynthesis fuels processes and conversions in the total biofilm community,
      including the metabolism of heterotrophic organisms. A matrix of polymeric
      substances secreted by phototrophs and heterotrophs enhances the attachment of
      the biofilm community. This review discusses the actual and potential
      applications of phototrophic biofilms in wastewater treatment, bioremediation,
      fish-feed production, biohydrogen production, and soil improvement.

PMID- 19396357
TI  - Dietary energy density in relation to subsequent changes of weight and waist
      circumference in European men and women.
AB  - BACKGROUND: Experimental studies show that a reduction in dietary energy density
      (ED) is associated with reduced energy intake and body weight. However, few
      observational studies have investigated the role of ED on long-term weight and
      waist circumference change. METHODS AND PRINCIPAL FINDINGS: This population-based
      prospective cohort study included 89,432 participants from five European
      countries with mean age 53 years (range: 20-78 years) at baseline and were
      followed for an average of 6.5 years (range: 1.9-12.5 years). Participants were
      free of cancer, cardiovascular diseases and diabetes at baseline. ED was
      calculated as the energy intake (kcal) from foods divided by the weight (g) of
      foods. Multiple linear regression analyses were performed to investigate the
      associations of ED with annual weight and waist circumference change. Mean ED was
      1.7 kcal/g and differed across study centers. After adjusting for baseline
      anthropometrics, demographic and lifestyle factors, follow-up duration and energy
      from beverages, ED was not associated with weight change, but significantly
      associated with waist circumference change overall. For 1 kcal/g ED, the annual
      weight change was -42 g/year [95% confidence interval (CI): -112, 28] and annual
      waist circumference change was 0.09 cm/year [95% CI: 0.01, 0.18]. In participants
      with baseline BMI<25 kg/m(2), 1 kcal/g ED was associated with a waist
      circumference change of 0.17 cm/year [95% CI: 0.09, 0.25]. CONCLUSION: Our
      results suggest that lower ED diets do not prevent weight gain but have a weak
      yet potentially beneficial effect on the prevention of abdominal obesity as
      measured by waist circumference.

PMID- 19396358
TI  - A new computational tool for the phenomenological analysis of multipassage tumor
      growth curves.
AB  - Multipassage experiments are performed by subcutaneous implantation in lab
      animals (usually mice) of a small number of cells from selected human lines.
      Tumor cells are then passaged from one mouse to another by harvesting them from a
      growing tumor and implanting them into other healthy animals. This procedure may
      be extremely useful to investigate the various mechanisms involved in the long
      term evolution of tumoral growth. It has been observed by several researchers
      that, contrary to what happens in in vitro experiments, there is a significant
      growth acceleration at each new passage. This result is explained by a new method
      of analysis, based on the Phenomenological Universalities approach. It is found
      that, by means of a simple rescaling of time, it is possible to collapse all the
      growth curves, corresponding to the successive passages, into a single curve,
      belonging to the Universality Class U2. Possible applications are proposed and
      the need of further experimental evidence is discussed.

PMID- 19396359
TI  - Exploring the relationship between semantics and space.
AB  - The asymmetric distribution of human spatial attention has been repeatedly
      documented in both patients and healthy controls. Biases in the distribution of
      attention and/or in the mental representation of space may also affect some
      aspects of language processing. We investigated whether biases in attention
      and/or mental representation of space affect semantic representations. In
      particular, we investigated whether semantic judgments could be modulated by the
      location in space where the semantic information was presented and the role of
      the left and right parietal cortices in this task. Healthy subjects were
      presented with three pictures arranged horizontally (one middle and two outer
      pictures) of items belonging to the same semantic category. Subjects were asked
      to indicate the spatial position in which the semantic distance between the outer
      and middle pictures was smaller. Subjects systematically overestimated the
      semantic distance of items presented in the right side of space. We explored the
      neural correlates underpinning this bias using rTMS over the left and right
      parietal cortex. rTMS of the left parietal cortex selectively reduced this
      rightward bias. Our findings suggest the existence of an attentional and/or
      mental representational bias in semantic judgments, similar to that observed for
      the processing of space and numbers. Spatial manipulation of semantic material
      results in the activation of specialised attentional resources located in the
      left hemisphere.

PMID- 19396360
TI  - Modern subsurface bacteria in pristine 2.7 Ga-old fossil stromatolite drillcore
      samples from the Fortescue Group, Western Australia.
AB  - BACKGROUND: Several abiotic processes leading to the formation of life-like
      signatures or later contamination with actual biogenic traces can blur the
      interpretation of the earliest fossil record. In recent years, a large body of
      evidence showing the occurrence of diverse and active microbial communities in
      the terrestrial subsurface has accumulated. Considering the time elapsed since
      Archaean sedimentation, the contribution of subsurface microbial communities
      postdating the rock formation to the fossil biomarker pool and other biogenic
      remains in Archaean rocks may be far from negligible. METHODOLOGY/PRINCIPAL
      FINDINGS: In order to evaluate the degree of potential contamination of Archean
      rocks by modern microorganisms, we looked for the presence of living indigenous
      bacteria in fresh diamond drillcores through 2,724 Myr-old stromatolites
      (Tumbiana Formation, Fortescue Group, Western Australia) using molecular methods
      based on the amplification of small subunit ribosomal RNA genes (SSU rDNAs). We
      analyzed drillcore samples from 4.3 m and 66.2 m depth, showing signs of
      meteoritic alteration, and also from deeper "fresh" samples showing no apparent
      evidence for late stage alteration (68 m, 78.8 m, and 99.3 m). We also analyzed
      control samples from drilling and sawing fluids and a series of laboratory
      controls to establish a list of potential contaminants introduced during sample
      manipulation and PCR experiments. We identified in this way the presence of
      indigenous bacteria belonging to Firmicutes, Actinobacteria, and Alpha-, Beta-,
      and Gammaproteobacteria in aseptically-sawed inner parts of drillcores down to at
      least 78.8 m depth. CONCLUSIONS/SIGNIFICANCE: The presence of modern bacterial
      communities in subsurface fossil stromatolite layers opens the possibility that a
      continuous microbial colonization had existed in the past and contributed to the
      accumulation of biogenic traces over geological timescales. This finding casts
      shadow on bulk analyses of early life remains and makes claims for morphological,
      chemical, isotopic, and biomarker traces syngenetic with the rock unreliable in
      the absence of detailed contextual analyses at microscale.

PMID- 19396361
TI  - New concepts in molecular imaging: non-invasive MRI spotting of proteolysis using
      an Overhauser effect switch.
AB  - BACKGROUND: Proteolysis, involved in many processes in living organisms, is
      tightly regulated in space and time under physiological conditions. However
      deregulation can occur with local persistent proteolytic activities, e.g. in
      inflammation, cystic fibrosis, tumors, or pancreatitis. Furthermore, little is
      known about the role of many proteases, hence there is a need of new imaging
      methods to visualize specifically normal or disease-related proteolysis in intact
      bodies. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, a new concept for non
      invasive proteolysis imaging is proposed. Overhauser-enhanced Magnetic Resonance
      Imaging (OMRI) at 0.2 Tesla was used to monitor the enzymatic hydrolysis of a
      nitroxide-labeled protein. In vitro, image intensity switched from 1 to 25 upon
      proteolysis due to the associated decrease in the motional correlation time of
      the substrate. The OMRI experimental device used in this study is consistent with
      protease imaging in mice at 0.2 T without significant heating. Simulations show
      that this enzymatic-driven OMRI signal switch can be obtained at lower
      frequencies suitable for larger animals or humans. CONCLUSIONS/SIGNIFICANCE: The
      method is highly sensitive and makes possible proteolysis imaging in three
      dimensions with a good spatial resolution. Any protease could be targeted
      specifically through the use of taylor-made cleavable macromolecules. At short
      term OMRI of proteolysis may be applied to basic research as well as to evaluate
      therapeutic treatments in small animal models of experimental diseases.

PMID- 19396362
TI  - Activation of the left inferior frontal gyrus in the first 200 ms of reading:
      evidence from magnetoencephalography (MEG).
AB  - BACKGROUND: It is well established that the left inferior frontal gyrus plays a
      key role in the cerebral cortical network that supports reading and visual word
      recognition. Less clear is when in time this contribution begins. We used
      magnetoencephalography (MEG), which has both good spatial and excellent temporal
      resolution, to address this question. METHODOLOGY/PRINCIPAL FINDINGS: MEG data
      were recorded during a passive viewing paradigm, chosen to emphasize the stimulus
      driven component of the cortical response, in which right-handed participants
      were presented words, consonant strings, and unfamiliar faces to central vision.
      Time-frequency analyses showed a left-lateralized inferior frontal gyrus (pars
      opercularis) response to words between 100-250 ms in the beta frequency band that
      was significantly stronger than the response to consonant strings or faces. The
      left inferior frontal gyrus response to words peaked at approximately 130 ms.
      This response was significantly later in time than the left middle occipital
      gyrus, which peaked at approximately 115 ms, but not significantly different from
      the peak response in the left mid fusiform gyrus, which peaked at approximately
      140 ms, at a location coincident with the fMRI-defined visual word form area
      (VWFA). Significant responses were also detected to words in other parts of the
      reading network, including the anterior middle temporal gyrus, the left posterior
      middle temporal gyrus, the angular and supramarginal gyri, and the left superior
      temporal gyrus. CONCLUSIONS/SIGNIFICANCE: These findings suggest very early
      interactions between the vision and language domains during visual word
      recognition, with speech motor areas being activated at the same time as the
      orthographic word-form is being resolved within the fusiform gyrus. This
      challenges the conventional view of a temporally serial processing sequence for
      visual word recognition in which letter forms are initially decoded, interact
      with their phonological and semantic representations, and only then gain access
      to a speech code.

PMID- 19396363
TI  - Alterations in heparan sulfate in the vessel in response to vascular injury in
      the mouse.
AB  - Heparan sulfate (HS) is ubiquitous throughout the human body. The backbone of HS
      is composed of many types of sugars. HS serves as a docking site for a vast array
      of protein ligands. Recent evidence suggests a unique diversity in HS structure
      that alters protein binding and protein function. This diversity in HS structure
      has been overlooked till now. The goal of this study was to determine whether
      femoral artery wire injury modified HS structure. Femoral artery wire injury was
      performed in 16-week-old male C57BL6 mice. Transcript levels of a panel of
      enzymes that regulate HS fine structure, including N-deacetylase-N
      sulfotransferases (Ndst) 1 and 2, exostoses (Ext) 1 and 2, C5 epimerase, and 2-O
      and 6-O sulfotransferases, were quantified with real-time quantitative polymerase
      chain reaction at 7 and 14 days post injury. All enzymes showed significant
      alterations in messenger RNA expression in response to injury. Ndst1, the most
      prevalent isoform, exhibited a 20-fold increase in response to injury. Injury
      induced significant alterations in fine structure specially increases in N
      sulfated disaccharides at 14 days post injury. Vascular injury invokes
      transcriptional regulation of the enzymes that regulate HS structure, as well as
      changes in the pattern of HS chains in the vessel wall 14 days post injury. These
      findings may be important as the foundation of altered growth factor and
      chemokine binding in the process of vascular remodeling.

PMID- 19396364
TI  - Joint modelling of paired sparse functional data using principal components.
AB  - We propose a modelling framework to study the relationship between two paired
      longitudinally observed variables. The data for each variable are viewed as
      smooth curves measured at discrete time-points plus random errors. While the
      curves for each variable are summarized using a few important principal
      components, the association of the two longitudinal variables is modelled through
      the association of the principal component scores. We use penalized splines to
      model the mean curves and the principal component curves, and cast the proposed
      model into a mixed-effects model framework for model fitting, prediction and
      inference. The proposed method can be applied in the difficult case in which the
      measurement times are irregular and sparse and may differ widely across
      individuals. Use of functional principal components enhances model interpretation
      and improves statistical and numerical stability of the parameter estimates.

PMID- 19396365
TI  - Bayesian Analysis of Multivariate Nominal Measures Using Multivariate Multinomial
      Probit Models.
AB  - The multinomial probit model has emerged as a useful framework for modeling
      nominal categorical data, but extending such models to multivariate measures
      presents computational challenges. Following a Bayesian paradigm, we use a Markov
      chain Monte Carlo (MCMC) method to analyze multivariate nominal measures through
      multivariate multinomial probit models. As with a univariate version of the
      model, identification of model parameters requires restrictions on the covariance
      matrix of the latent variables that are introduced to define the probit
      specification. To sample the covariance matrix with restrictions within the MCMC
      procedure, we use a parameter-extended Metropolis-Hastings algorithm that
      incorporates artificial variance parameters to transform the problem into a set
      of simpler tasks including sampling an unrestricted covariance matrix. The
      parameter-extended algorithm also allows for flexible prior distributions on
      covariance matrices. The prior specification in the method described here
      generalizes earlier approaches to analyzing univariate nominal data, and the
      multivariate correlation structure in the method described here generalizes the
      autoregressive structure proposed in previous multiperiod multinomial probit
      models. Our methodology is illustrated through a simulated example and an
      application to a cancer-control study aiming to achieve early detection of breast
      cancer.

PMID- 19396366
TI  - Splicing of mRNA precursors: the role of RNAs and proteins in catalysis.
AB  - Splicing of mRNA precursors was discovered over 30 years ago. It is one of the
      most complex steps in gene expression and therefore must be tightly controlled to
      ensure that splicing occurs efficiently and accurately. Splicing takes place in a
      large complex, the spliceosome, which contains approximately 200 proteins and
      five small RNAs (U snRNAs). Since its discovery, much work has been done to
      elucidate the pathway of the chemical reaction as well as the proteins and RNAs
      involved in catalysis. A variety of studies have established the potential for U2
      and U6 snRNAs to play a role in splicing catalysis, raising the possibility that
      the spliceosome is a ribozyme. If correct, this would point to the spliceosomal
      proteins playing a supporting role during splicing. On the other hand, it may be
      that proteins contribute more directly to the spliceosomal active site, with the
      highly evolutionarily conserved Prp8 protein being an excellent candidate. This
      review will concentrate on recent work on splicing catalysis, and on elucidating
      the possible roles proteins play in this process.

PMID- 19396368
TI  - Fast predictions of thermodynamics and kinetics of protein-protein recognition
      from structures: from molecular design to systems biology.
AB  - The increasing call for an overall picture of the interactions between the
      components of a biological system that give rise to the observed function is
      often summarized by the expression systems biology. Both the interpretative and
      predictive capabilities of holistic models of biochemical systems, however,
      depend to a large extent on the level of physico-chemical knowledge of the
      individual molecular interactions making up the network. This review is focused
      on the structure-based quantitative characterization of protein-protein
      interactions, ubiquitous in any biochemical pathway. Recently developed, fast and
      effective computational methods are reviewed, which allow the assessment of
      kinetic and thermodynamic features of the association-dissociation processes of
      protein complexes, both in water soluble and membrane environments. The
      performance and the accuracy of fast and semi-empirical structure-based methods
      have reached comparable levels with respect to the classical and more elegant
      molecular simulations. Nevertheless, the broad accessibility and lower
      computational cost provide the former methods with the advantageous possibility
      to perform systems-level analyses including extensive in silico mutagenesis
      screenings and large-scale structural predictions of multiprotein complexes.

PMID- 19396367
TI  - Structure and mechanism of beta-hairpin antimicrobial peptides in lipid bilayers
      from solid-state NMR spectroscopy.
AB  - The membrane-bound structure, lipid interaction, and dynamics of the arginine
      rich beta-hairpin antimicrobial peptide PG-1 as studied by solid-state NMR are
      highlighted here. A variety of solid-state NMR techniques, including paramagnetic
      relaxation enhancement, (1)H and (19)F spin diffusion, dipolar recoupling
      distance experiments, and 2D anisotropic-isotropic correlation experiments, are
      used to elucidate the structural basis for the membrane disruptive activity of
      this representative beta-hairpin antimicrobial peptide. We found that PG-1
      structure is membrane dependent: in bacteria-mimetic anionic lipid membranes the
      peptide forms oligomeric transmembrane beta-barrels, whereas in cholesterol-rich
      membranes mimicking eukaryotic cells the peptide forms beta-sheet aggregates on
      the surface of the bilayer. PG-1 causes toroidal pore defects in the anionic
      membrane, suggesting that the cationic arginine residues drag the lipid phosphate
      groups along as the peptide inserts. Mutation of PG-1 to reduce the number of
      cationic residues or to change the arginine guanidinium structure significantly
      changes the degree of insertion and orientation of the peptide in the lipid
      membrane, resulting in much weaker antimicrobial activities.

PMID- 19396369
TI  - Functional models for large-scale gene regulation networks: realism and fiction.
AB  - High-throughput experiments are shedding light on the topology of large
      regulatory networks and at the same time their functional states, namely the
      states of activation of the nodes (for example transcript or protein levels) in
      different conditions, times, environments. We now possess a certain amount of
      information about these two levels of description, stored in libraries, databases
      and ontologies. A current challenge is to bridge the gap between topology and
      function, i.e. developing quantitative models aimed at characterizing the
      expression patterns of large sets of genes. However, approaches that work well
      for small networks become impossible to master at large scales, mainly because
      parameters proliferate. In this review we discuss the state of the art of large
      scale functional network models, addressing the issue of what can be considered
      as "realistic" and what the main limitations may be. We also show some directions
      for future work, trying to set the goals that future models should try to
      achieve. Finally, we will emphasize the possible benefits in the understanding of
      biological mechanisms underlying complex multifactorial diseases, and in the
      development of novel strategies for the description and the treatment of such
      pathologies.

PMID- 19396370
TI  - Moonlighting proteins--an update.
AB  - A growing number of diverse proteins are being identified that moonlight.
      Moonlighting proteins comprise an interesting subset of multifunctional proteins
      in which the two functions are found in a single polypeptide chain. They do not
      include proteins that are multifunctional due to gene fusions, families of
      homologous proteins, splice variants, or promiscuous enzyme activities. This
      review summarizes recent discoveries that add to the list of known moonlighting
      proteins. They include several different kinds of proteins and combinations of
      functions. In one case, a novel DNA binding function was found for a biosynthetic
      enzyme through a proteomics microarray project. The review also summarizes recent
      X-ray crystal structures that provide clues to the molecular mechanisms of one or
      both functions, and in some cases how a protein can switch between functions. In
      addition, the possibility that many proteins with intrinsically unstructured
      regions might also moonlight is discussed.

PMID- 19396371
TI  - Gut microbiome modulates the toxicity of hydrazine: a metabonomic study.
AB  - The influence of gut microbiota on the toxicity and metabolism of hydrazine has
      been investigated in germ-free and 'conventional' Sprague Dawley rats using 1H
      NMR based metabonomic analysis of urine and plasma. Toxicity was more severe in
      germ-free rats compared with conventional rats for equivalent exposures
      indicating that bacterial presence altered the nature or extent of response to
      hydrazine and that the toxic response can vary markedly in the absence of a
      functional microbiome.

PMID- 19396372
TI  - Receptor-independent modulation of reconstituted Galpha(i) protein mediated by
      liposomes.
AB  - A cationic amphiphile, BC5 (N-pentadecylpiperidin-4-amine), was recently designed
      and tested for its ability to directly stimulate the activity of recombinant
      Galpha inhibitory subunits. However, amphiphilic drugs can self-associate and
      bind to plasma membranes, causing undesired side effects. In this contribution,
      we report on the incorporation of BC5 in 1,2-dipalmytoyl-sn-glycerophosphocoline
      (DPPC) liposomes and on the characterization of the mixed DPPC/BC5 systems at
      various lipid/drug mole ratios by means of dynamic light scattering, differential
      scanning calorimetry and fluorescence spectroscopy. The myristoylated Galpha(i)
      subunit (Galpha-mir) was reconstituted in 1,2-dimiristoyl-sn-glycerophosphocoline
      (DMPC) bilayers, as a mimic of the drug target. We compare several reconstitution
      procedures in liposomes and present for the first time a complete
      characterization of a Galpha subunit reconstitution in model membranes in terms
      of protein activity as a function of the reconstitution protocol. The
      incorporation of the drug in DPPC bilayers resulted in enhanced Gi-modulating
      efficiency (evaluated in terms of binding to GTPgammaS (guanosine-5'-(gamma-thio)
      triphosphate)). A correlation of the physico-chemical features and binding
      activity of protein-containing membrane model is proposed.

PMID- 19396373
TI  - Genome-scale reconstruction of the metabolic network in Yersinia pestis, strain
      91001.
AB  - The gram-negative bacterium Yersinia pestis, the aetiological agent of bubonic
      plague, is one of the deadliest pathogens known to man. Despite its historical
      reputation, plague is a modern disease which annually afflicts thousands of
      people. Public safety considerations greatly limit clinical experimentation on
      this organism and thus development of theoretical tools to analyze the
      capabilities of this pathogen is of utmost importance. Here, we report the first
      genome-scale metabolic model of Yersinia pestis biovar Mediaevalis based both on
      its recently annotated genome, and physiological and biochemical data from the
      literature. Our model demonstrates excellent agreement with Y. pestis' known
      metabolic needs and capabilities. Since Y. pestis is a meiotrophic organism, we
      have developed CryptFind, a systematic approach to identify all candidate cryptic
      genes responsible for known and theoretical meiotrophic phenomena. In addition to
      uncovering every known cryptic gene for Y. pestis, our analysis of the rhamnose
      fermentation pathway suggests that betB is the responsible cryptic gene. Despite
      all of our medical advances, we still do not have a vaccine for bubonic plague.
      Recent discoveries of antibiotic resistant strains of Yersinia pestis coupled
      with the threat of plague being used as a bioterrorism weapon compel us to
      develop new tools for studying the physiology of this deadly pathogen. Using our
      theoretical model, we can study the cell's phenotypic behavior under different
      circumstances and identify metabolic weaknesses that may be harnessed for the
      development of therapeutics. Additionally, the automatic identification of
      cryptic genes expands the usage of genomic data for pharmaceutical purposes.

PMID- 19396374
TI  - Chemical genomics identifies compounds affecting Xenopus laevis pigment cell
      development.
AB  - A forward chemical genomic screen was carried out using Xenopus laevis embryos to
      identify compounds disrupting pigmented cell development, including the retinal
      pigment epithelial (RPE) layer of the eye and the melanophores (melanocytes).
      Phenotypes showing changes in cell migration, morphology and pigmentation were
      observed. The screen also identified compounds affecting other aspects of Xenopus
      development including general patterning and morphogenesis, eye development and
      edema formation. Evidence is presented for the molecular targets of three of the
      compounds identified. Xenopus melanophore and human melanoma cell lines were also
      utilised in follow-up cell morphology assays. Chemical genomic screens of this
      type have an important role to play in the identification of novel compounds
      providing new molecular tools, and biological information, along with
      identification of new protein targets and leads for potential therapeutic agents.

PMID- 19396375
TI  - Protein lethality investigated in terms of long range dynamical interactions.
AB  - The relationship between network structure/dynamics and biological function
      constitutes a fundamental issue in systems biology. However, despite many related
      investigations, the correspondence between structure and biological functions is
      not yet fully understood. A related subject that has deserved particular
      attention recently concerns how essentiality is related to the structure and
      dynamics of protein interactions. In the current work, protein essentiality is
      investigated in terms of long range influences in protein-protein interaction
      networks by considering simulated dynamical aspects. This analysis is performed
      with respect to outward activations, an approach which models the propagation of
      interactions between proteins by considering self-avoiding random walks. The
      obtained results are compared to protein local connectivity. Both the
      connectivity and the outward activations were found to be strongly related to
      protein essentiality.

PMID- 19396376
TI  - Chitosan: a novel platform in proton-driven DNA strand rearrangement actuation.
AB  - Nanometre-scaled DNA machine based on molecular recognition properties of DNA has
      now become a powerful tool in nanodevices, miniaturized structure, and
      nanofabrication. The common principle behind designing a DNA nanomachine is DNA
      strand exchange or rearrangement, which is solely controlled by the stabilization
      through associative and dissociative forces arising from base pair interaction of
      DNA molecules. Thus, highly effective DNA reaction actuator will make DNA
      nanomachine more flexible, controllable, and powerful device. Here, we report the
      novel polymer-mediated platform in proton-driven DNA strand rearrangement
      actuation. This cationic low molecular weight water-soluble chitosan (LMWSC)
      exhibited pH-dependent complexation with oligodeoxynucleotides (ODN). It formed
      complex with ODN only at low pH and accelerated the DNA strand exchange (or
      rearrangement) reaction between dsDNA and its complementary ssDNA at pH 5.0.
      However, no complexation was observed between LMWSC and ODN at neutral pH. We
      assume that at physiological pH, LMWSC is not protonated enough for formation of
      complex with ODN. Therefore, it can not diminish the electrostatic repulsion
      among the negatively charged DNA strands of the three-stranded intermediate
      formed during the strand exchange reaction. In contrast, LMWSC becomes positively
      charged at acidic pH, and it stabilizes the three-stranded intermediate by
      spreading out the accumulated counter-ions and increasing the entropy of the
      system. This fascinating observation prompted us to believe that this intelligent
      proton-driven DNA reaction actuator has a potential for the precise control of
      DNA nanomachine and would be applied for operating and controlling nanoscaled
      machine.

PMID- 19396377
TI  - Molecular systems biology of ErbB1 signaling: bridging the gap through multiscale
      modeling and high-performance computing.
AB  - The complexity in intracellular signaling mechanisms relevant for the conquest of
      many diseases resides at different levels of organization with scales ranging
      from the subatomic realm relevant to catalytic functions of enzymes to the
      mesoscopic realm relevant to the cooperative association of molecular assemblies
      and membrane processes. Consequently, the challenge of representing and
      quantifying functional or dysfunctional modules within the networks remains due
      to the current limitations in our understanding of mesoscopic biology, i.e., how
      the components assemble into functional molecular ensembles. A multiscale
      approach is necessary to treat a hierarchy of interactions ranging from molecular
      (nm, ns) to signaling (microm, ms) length and time scales, which necessitates the
      development and application of specialized modeling tools. Complementary to
      multiscale experimentation (encompassing structural biology, mechanistic
      enzymology, cell biology, and single molecule studies) multiscale modeling offers
      a powerful and quantitative alternative for the study of functional intracellular
      signaling modules. Here, we describe the application of a multiscale approach to
      signaling mediated by the ErbB1 receptor which constitutes a network hub for the
      cell's proliferative, migratory, and survival programs. Through our multiscale
      model, we mechanistically describe how point-mutations in the ErbB1 receptor can
      profoundly alter signaling characteristics leading to the onset of oncogenic
      transformations. Specifically, we describe how the point mutations induce
      cascading fragility mechanisms at the molecular scale as well as at the scale of
      the signaling network to preferentially activate the survival factor Akt. We
      provide a quantitative explanation for how the hallmark of preferential Akt
      activation in cell-lines harboring the constitutively active mutant ErbB1
      receptors causes these cell-lines to be addicted to ErbB1-mediated generation of
      survival signals. Consequently, inhibition of ErbB1 activity leads to a
      remarkable therapeutic response in the addicted cell lines.

PMID- 19396378
TI  - Stimulation of lung carcinoma cell growth by fibronectin-integrin signalling.
AB  - Throughout many countries, lung cancer will kill more people this year than
      malignancies related to breast, prostate, colon, liver, kidney and melanoma
      combined. Despite recent advances in understanding the molecular biology of lung
      carcinoma and the introduction of multiple new chemotherapeutic agents for its
      treatment, its dismal five-year survival rate (<15%) has not changed
      substantially. The lack of advancement in this area reflects the limited
      knowledge available concerning the factors that promote oncogenic transformation
      and proliferation of carcinoma cells in the lung. Malignant transformation plays
      a key role in tumor growth and invasion; however, other factors such as the
      surrounding stroma, local growth factors, vascularity, and systemic hormones are
      important contributors as well. We believe that the composition of the lung
      extracellular matrix is also important due to its ability to affect malignant
      cell behavior in vitro. The matrix glycoprotein fibronectin, for example, is
      highly expressed in chronic lung disorders where most lung carcinomas are
      identified. This document reviews information that implicates fibronectin in the
      stimulation of lung carcinoma cell growth. Data available to date indicate that
      by binding to specific integrin receptors expressed on the surface of tumor
      cells, fibronectin stimulates intracellular signals implicated in the
      pathobiology of lung carcinogenesis and lung tumor chemoresistance including
      mitogen-activated protein kinases, GTPases, and the PI3-kinase/Akt/mTOR pathway.
      Thus, integrin-mediated signals triggered by fibronectin in tumor cells represent
      promising targets for the development of novel anti-cancer strategies.

PMID- 19396379
TI  - Towards quantitative predictions in cell biology using chemical properties of
      proteins.
AB  - It has recently been suggested that the concentrations of proteins in the cell
      are tuned towards their critical values, and that the alteration of this balance
      often results in misfolding diseases. This concept is intriguing because the in
      vivo concentrations of proteins are closely regulated by complex cellular
      processes, while their critical concentrations are primarily determined by the
      chemical characters of their amino acid sequences. We discuss here how the
      presence of a link between the upper levels of in vivo concentrations and
      critical concentrations offers an opportunity to make quantitative predictions in
      cell biology based on the chemical properties of proteins.

PMID- 19396381
TI  - Molecular mechanism of intestinal permeability: interaction at tight junctions.
AB  - The intestinal barrier plays a critical role in humans in the transport of
      nutrients and macromolecules. At the same time, it has to provide an effective
      barrier to harmful macromolecules and microorganisms. The tight junction (TJ) is
      an essential component of this barrier. The junctional complexes of the plasma
      membrane are not simply epithelial barriers in paracellular transport or barriers
      preventing diffusion in the plasma membrane, but also contain proteins involved
      in signal transduction and the maintenance of the physiological epithelial cell
      state. Occludin, claudin, junctional adhesion molecules, and the coxsackie virus
      and adenovirus receptor are the major components of TJs. This article highlights
      the structure and function of TJs as well as the molecular interactions occurring
      during permeation through TJs.

PMID- 19396380
TI  - Structural dissection of the extracellular moieties of the type III secretion
      apparatus.
AB  - Many Gram-negative bacterial pathogens use type III secretion systems (TTSSs) for
      subverting the normal cellular functions of their target eukaryotic cells. The
      type III secretion apparatus (TTSA) functions like a syringe to inject proteins
      through an external needle and into a target cell's membrane and cytosol. The
      TTSA basal body spans the bacterial inner and outer membranes, and the external
      needle is topped with a tip complex that controls the secretion and delivery of
      translocator and effector proteins. Recently solved structures of TTSA proteins
      have greatly advanced our understanding of shared themes in apparatus assembly
      and function. In this highlight, the structure-function of TTSA needle and tip
      complex proteins are described and common themes discussed.

PMID- 19396382
TI  - Specificity of protein lysine methyltransferases and methods for detection of
      lysine methylation of non-histone proteins.
AB  - Post translational modification of histone proteins including lysine methylation
      is an important epigenetic mark, essential for gene regulation and development.
      Recently, several examples of lysine methylation of non-histone proteins have
      been discovered suggesting that this is a common post-translational modification
      for regulation of protein activity. Here, we review assays for the detection of
      protein methylation based on mass spectrometry, radiolabel and immunological
      approaches using protein and peptide substrates including application of SPOT
      peptide arrays. Candidates for new methylation targets of protein
      methyltransferases can be predicted using the specificity of the enzyme and
      protein interaction data.

PMID- 19396384
TI  - Effective delivery of IgG-antibodies into infected cells via dendritic molecular
      transporter conjugate IgGMT.
AB  - IgG antibody-transporter conjugates enable intracellular uptake of biologically
      active IgG antibodies that inhibit viral mediated syncytia formation in
      respiratory syncytial virus green fluorescent protein (RSV-GFP) infected human
      epithelial cells (HEp-2).

PMID- 19396385
TI  - Fragile X mental retardation protein recognition of G quadruplex structure per se
      is sufficient for high affinity binding to RNA.
AB  - Fragile X syndrome, the most common form of inherited mental retardation is
      caused by the expansion of a CGG trinucleotide repeat in the fragile X mental
      retardation 1 (fmr1) gene. The abnormal expansion of the CGG repeat causes
      hypermethylation and subsequent silencing of the fmr1 gene, resulting in the loss
      of the fragile X mental retardation protein (FMRP). FMRP has been shown to use
      its arginine-glycine-glycine rich region (RGG box) to bind to messenger RNAs that
      form G quadruplex structures. Several studies reported that the G quadruplex RNA
      recognition alone is not sufficient for FMRP RGG box binding and that an
      additional stem and/or a G quadruplex-stem junction region may also be important
      in recognition. In this study we have used biophysical methods such as
      fluorescence, UV, CD and NMR spectroscopy to demonstrate that the recognition of
      the RNA G quadruplex structure per se, in the absence of a stem region, is
      sufficient for the FMRP high affinity and specific binding. These findings
      indicate that the presence of a stem structure in some of the FMRP G quadruplex
      forming mRNAs is not a requirement for protein recognition as previously
      believed, but rather for the proper formation of the correct RNA G quadruplex
      structure recognized by FMRP.

PMID- 19396383
TI  - Droplet interface bilayers.
AB  - Droplet interface bilayers (DIBs) provide a superior platform for the biophysical
      analysis of membrane proteins. The versatile DIBs can also form networks, with
      features that include built-in batteries and sensors.

PMID- 19396386
TI  - Deliberate self-harm in Oxford University students, 1993-2005: a descriptive and
      case-control study.
AB  - BACKGROUND: Deliberate self-harm (DSH; intentional self-poisoning or self-injury)
      is a major problem among young people and has been identified as one of the key
      mental health problems affecting students. METHOD: Data on DSH presentations to
      the general hospital in Oxford by Oxford University students were analysed for
      the 12-year period from 1993 to 2005. The characteristics of the students with
      DSH were compared with those of age-matched DSH controls in the Oxford City area.
      RESULTS: Problems with academic work, relationships with family, partners and
      friends were most likely to contribute to DSH episodes in students. Many
      experienced problems with psychiatric disorders and social isolation. The
      frequency of eating disorders was very high in students, and contributed to DSH
      significantly more often than in controls. Fewer students than controls self
      poisoned in the DSH episode, fewer had personality disorder and fewer had
      problems with physical health, finance, housing and violence. Alcohol consumption
      in association with DSH and alcohol-related problems were common in both students
      and controls. Male students had significantly higher suicide intent than
      controls. Many students were referred to the university counselling service for
      follow-up, a resource not available to non-student controls. CONCLUSIONS:
      Comparison of university students following DSH with age-matched controls has
      shown key differences in psychiatric characteristics, problems contributing to
      DSH and aftercare offered. These findings may help in the design of targeted self
      harm prevention and management strategies for students.

PMID- 19396387
TI  - Ethics of cardiac transplantation in hypoplastic left heart syndrome.

PMID- 19396388
TI  - Analysis of ventricular hypertrabeculation and noncompaction using genetically
      engineered mouse models.
AB  - Ventricular trabeculation and compaction are two of the many essential steps for
      generating a functionally competent ventricular wall. A significant reduction in
      trabeculation is usually associated with ventricular compact zone deficiencies
      (hypoplastic wall), which commonly lead to embryonic heart failure and early
      embryonic lethality. In contrast, hypertrabeculation and lack of ventricular wall
      compaction (noncompaction) are closely related defects in cardiac embryogenesis
      associated with left ventricular noncompaction, a genetically heterogeneous
      disorder. Here we summarize our recent findings through the analyses of several
      genetically engineered mouse models that have defects in cardiac trabeculation
      and compaction. Our data indicate that cellular growth and differentiation
      signaling pathways are keys in these ventricular morphogenetic events.

PMID- 19396389
TI  - Portal vein branching pattern in anomalous right-sided round ligament.
AB  - OBJECTIVE: To study the relationship of anomalous right-sided round ligament with
      respect to branches of the portal vein. METHODS: We studied four patients of
      right-sided round ligament diagnosed radiologically in the last 5 years. 3-D
      volume rendered CECT abdominal images were analyzed for attachment of the round
      ligament in the liver in relation to portal venous anatomy and position of
      gallbladder. RESULTS: In all cases, a trifurcate pattern of portal venous
      branching was observed. Right-sided round ligament was attached at the point of
      divergence of the right anterior portal vein. The region to the left of the point
      of its attachment drained into the middle hepatic vein while the region to the
      right of the point of attachment drained into the right hepatic vein. The left
      portal vein branched into posterior and paramedian branches. Right, middle, and
      left hepatic veins were visualized having normal course in all cases. In all, the
      gallbladder was present to the left of the round ligament. CONCLUSIONS:
      Trifurcate pattern of portal vein branching in all four cases. Right-sided round
      ligament was attached to the bifurcation of the right anterior portal vein in all
      the cases. The left portal vein branched into posterior and paramedian branches.

PMID- 19396390
TI  - Long-term outcome of autoimmune pancreatitis.
AB  - PURPOSE: Autoimmune pancreatitis (AIP) is a unique form of pancreatitis and can
      be complicated with various extrapancreatic lesions. Little is known about the
      long-term clinical course of AIP. Here we aimed to document the clinical course
      of AIP. METHODS: For this study, we recruited 21 patients, averaging 66.5 years
      in age (range, 19-84 years) and observed them at a mean interval of 40.8 months
      (range, 18-130 months). Three of the patients were also diagnosed with
      retroperitoneal fibrosis, 3 had sialoadenitis, 2 had chronic thyroiditis, 1 had
      interstitial nephritis, and 1 had interstitial pneumonia. Three of the patients
      underwent surgical therapy, 12 patients received methylprednisolone (PSL)
      treatment, and the 6 remaining patients received no treatment. RESULTS:
      Enlargement of the pancreas was attenuated in all the PSL-treated patients. Seven
      of the 21 patients showed pancreatic atrophy, of whom 2 were non-PSL-treated
      patients. Three patients developed chronic pancreatitis. One patient was
      diagnosed with pancreatic cancer after 50 months of PSL therapy. CONCLUSIONS: As
      with chronic pancreatitis patients, AIP patients should be observed closely for
      abnormality in pancreatic function.

PMID- 19396391
TI  - Delayed post-traumatic saccular aneurysm of PICA in an adolescent.
AB  - Delayed traumatic intracranial aneurysms of the posterior circulation caused by
      nonpenetrating head injury are rare, especially in pediatric patients. The true
      incidence and natural history of these aneurysms are poorly understood. We report
      a case of a 15-year-old boy who initially presented with subarachnoid hemorrhage
      of the posterior fossa without any evidence of associated aneurysm. On a routine
      computed tomography of the head, however, he was found to have a saccular
      aneurysm of the proximal posterior inferior cerebellar artery. The patient was
      treated successfully by microsurgical clipping and PICA/PICA bypass.

PMID- 19396392
TI  - Neurovascular compression in painful tic convulsif.
AB  - This article describes the case of a 67-year-old woman who presented with a
      typical left hemifacial spasm of 8-month duration. After 2 months, she
      experienced lacinating and sharp shock-like pain in the left side of her face
      affecting the V1 and V2 territories and a discrete attenuation of nauseous reflex
      on the left side. CT angiography and MRI revealed significant compression of left
      cranial nerves V, VII, VIII, IX and X by a giant and tortuous vertebro-basilar
      arterial complex. This case illustrates the nonlinearity of the relationship
      between the presence of the stressor factor and the actual manifestation of the
      disease.

PMID- 19396393
TI  - Transcranial approach for treatment for traumatic optic chiasm syndrome.
AB  - To describe the visual outcome of patients with a traumatic optic chiasm
      syndrome, with and without neurosurgical intervention. The retrospective clinical
      interventional study included 14 patients, who either underwent a neurosurgical
      intervention with transcranial decompression of the optic canal (11 patients) in
      combination with a high-dosage systemic corticosteroid therapy or who received a
      high-dosage systemic corticosteroid treatment only (3 patients). In the surgical
      group, visual field improved after surgery in 6 (55%) patients and remained
      unchanged in 5 (45%) patients, while in none of the patients without surgery, the
      visual field improved. Neurosurgical decompression of the optic chiasm and optic
      nerve canal may be associated with a visual improvement in some patients with a
      traumatic optic chiasm syndrome.

PMID- 19396394
TI  - Role of Reelin in the development and maintenance of cortical lamination.
AB  - Reelin is a large extracellular matrix molecule, synthesized by early generated
      Cajal-Retzius cells in the marginal zone of the cortex. It plays an important
      role in the migration of cortical neurons and the development of cortical
      lamination. We recently discovered that Reelin is required not only for the
      formation of cortical layers during development but also for their maintenance in
      adulthood. Thus, decreased Reelin expression in a mouse model of epilepsy and in
      epileptic patients was accompanied by a loss of granule cell lamination, called
      granule cell dispersion, in the dentate gyrus of the hippocampal formation.
      Moreover, antibody blockade of Reelin in normal, adult mice resulted in granule
      cell dispersion. Collectively these findings point to a role for Reelin in the
      formation and maintenance of a laminated cortical structure. How does Reelin act
      on the cytoskeleton in the migration process of cortical neurons? It has been
      shown that Reelin signalling involves the lipoprotein receptors apolipoprotein E
      receptor 2 and very low density lipoprotein receptor, the adapter protein
      Disabled1, and phosphatidylinositol-3-kinase, but it has remained unclear how
      activation of the Reelin signalling cascade controls cytoskeletal reorganization.
      Here, we provide evidence that Reelin signalling leads to serine3 phosphorylation
      of cofilin, an actin-depolymerizing protein that promotes the disassembly of F
      actin. Phosphorylation at serine3 renders cofilin unable to depolymerize F-actin,
      thereby stabilizing the cytoskeleton. Phosphorylation of cofilin in the leading
      processes of migrating neurons anchors them to the marginal zone containing
      Reelin. Our results indicate that Reelin-induced stabilization of the neuronal
      cytoskeleton is an important component of Reelin's function in the development
      and maintenance of cortical architecture.

PMID- 19396395
TI  - Role of N-terminus of tyrosine hydroxylase in the biosynthesis of catecholamines.
AB  - Tyrosine hydroxylase (TH) catalyzes the conversion of L: -tyrosine to L: -dopa,
      which is the initial and rate-limiting step in the biosynthesis of catecholamines
      [CA; dopamine (DA), noradrenaline, and adrenaline], and plays a central role in
      the neurotransmission and hormonal actions of CA. Thus, TH is related to various
      neuro-psychiatric diseases such as TH deficiency, Parkinson's disease (PD), and
      schizophrenia. Four isoforms of human TH (hTH1-hTH4) are produced from a single
      gene by alternative mRNA splicing in the N-terminal region, whereas two isoforms
      exist in monkeys and only a single protein exist in all non-primate mammals. A
      catalytic domain is located within the C-terminal two-thirds of molecule, whereas
      the part of the enzyme controlling enzyme activity is assigned to the N-terminal
      end as the regulatory domain. The catalytic activity of TH is end product
      inhibited by CA, and the phosphorylation of Ser residues (Ser(19), Ser(31), and
      especially Ser(40) of hTH1) in the N-terminus relieves the CA-mediated
      inhibition. Ota and Nakashima et al. have investigated the role of the N-terminus
      of TH enzyme in the regulation of both the catalytic activity and the
      intracellular stability by producing various mutants of the N-terminus of hTH1.
      The expression of the following three enzymes, TH, GTP cyclohydrolase I, which
      synthesizes the tetrahydrobiopterin cofactor of TH, and aromatic-L: -amino acid
      decarboxylase, which produces DA from L: -dopa, were induced in the monkey
      striatum using harmless adeno-associated virus vectors, resulting in a remarkable
      improvement in the symptoms affecting PD model monkeys Muramatsu (Hum Gene Ther
      13:345-354, 2002). Increased knowledge concerning the amino acid sequences of the
      N-terminus of TH that control enzyme activity and stability will extend the
      spectrum of the gene-therapy approach for PD.

PMID- 19396396
TI  - Genomic and proteomic study to survey the mechanism of action of the anti
      Parkinson's disease drug, rasagiline compared with selegiline, in the rat
      midbrain.
AB  - The novel anti-Parkinson's disease (PD) drug, rasagiline (N-propargyl-1-(R)
      aminoindan), is a second generation of irreversible selective inhibitor of
      monoamine oxidase-B follows selegiline. In light of the recent large clinical
      study (phase III ADAGIO) reporting benefits in PD patients, it has been suggested
      that rasagiline could be the first PD treatment to receive the label
      neuroprotective "disease-modifying" drug. Indeed, rasagiline has been shown to
      have a broad neuroprotective activity against a variety of neurotoxins in
      preclinical models of neurodegenerative diseases and in cultured neuronal cells.
      In the present study, we have investigated the status of various molecular and
      biochemical markers in the rat midbrain following chronic treatments with
      rasagiline and selegiline, using proteomic and genomic analyses. Our findings
      demonstrated significant molecular changes induced by both drugs, at the protein
      and transcriptional levels, associated with neuronal differentiation, cell
      survival and death pathways, metabolism/oxidation stress, signaling system, and
      biomarkers of neurodegenerative disorders, which may be reflected in the clinical
      studies.

PMID- 19396397
TI  - Inequalities in cervical cancer screening in Eastern Europe: perspectives from
      Bulgaria and Romania.
AB  - OBJECTIVES: The incidence of cervical cancer in Eastern Europe has been on the
      rise, in contrast to the reduction in incidence in most countries of Western
      Europe. The objectives of the paper are to delineate the inequalities in cervical
      cancer screening in Romania and Bulgaria and identify explanations for these
      inequalities. METHODS: Representative samples of women - 1,099 in Bulgaria and
      1,053 in Romania, were interviewed through a structured questionnaire. RESULTS:
      We found multiple dimensions of inequalities in cervical cancer prevalence and
      prevention, including disparities in comparison to other countries, disparities
      due to socioeconomic status, education, residency and ethnicity, as well as
      differential barriers faced by women in access to screening and in relationships
      with providers. We identified mediators of the effects of socio-economic status
      on screening history. CONCLUSIONS: The study concludes that the effect of SES on
      screening is mediated mainly by the structural barriers in accessing the
      healthcare system, as well as women's perceptions of the multiple costs of the
      smear. These conclusions are relevant to the development of national screening
      programs and health promotion in the two countries.

PMID- 19396398
TI  - Neighbourhood socioeconomic indicators and depressive symptoms in the Czech
      Republic: a population based study.
AB  - OBJECTIVES: Previous research shows only limited evidence on the contextual
      (neighbourhood-based) socioeconomic influences on mental health and depression.
      We investigated the association between individual and neighbourhood
      socioeconomic characteristics and depressive symptoms in the Czech Republic.
      METHODS: Dichotomized CESD score of depressive symptoms was used as the outcome
      in a random sample of 3534 men and 4082 women aged 45-69 years in the Czech
      HAPIEE Study. 220 small areas were characterized by the proportion of university
      educated persons and the proportion of unemployed from the economically active
      population in the 2001 Census. Multilevel logistic regression was used for the
      analysis. RESULTS: After controlling for individual-level variables, the effects
      of area-based characteristics were largely eliminated. The strongest area-based
      effect was that of the proportion of university educated persons; the ORs for
      2(nd), 3(rd) and 4(th) quartile, compared with the 1(st) quartile, were 1.02,
      0.93, and 0.82, respectively (p-value for trend 0.06). There were no cross-level
      interactions between socioeconomic variables. CONCLUSIONS: The effects of
      neighbourhood characteristics in this study were largely explained by individual
      socioeconomic variables.

PMID- 19396400
TI  - Acute left ventricular dysfunction induced by a panHER and VEGFR tyrosine kinase
      inhibitor in a phase I trial.
AB  - Tyrosine kinase inhibitors (TKI) or monoclonal antibodies targeting EGFR, HER2 or
      VEGFR receptors have demonstrated substantial clinical benefit in patients with
      advanced breast cancer, colon cancer, head and neck cancer, non-small cell lung
      cancer, and renal cell carcinoma. Nevertheless, these drugs have some target
      related adverse effects, particularly cardiovascular toxicities. We report here
      the case of a patient included in a phase I trial of a new compound, a tyrosine
      kinase inhibitor targeting HER1, HER2, HER4 and VEGFR2. The patient developed
      during this treatment an acute and transient left ventricular systolic
      dysfunction. Careful management of this adverse effect allowed the patient to
      continue therapy and to achieve a major partial response.

PMID- 19396399
TI  - Aptamers against prion proteins and prions.
AB  - Prion diseases are fatal neurodegenerative and infectious disorders of humans and
      animals, characterized by structural transition of the host-encoded cellular
      prion protein (PrP(c)) into the aberrantly folded pathologic isoform PrP(Sc).
      RNA, DNA or peptide aptamers are classes of molecules which can be selected from
      complex combinatorial libraries for high affinity and specific binding to prion
      proteins and which might therefore be useful in diagnosis and therapy of prion
      diseases. Nucleic acid aptamers, which can be chemically synthesized, stabilized
      and immobilized, appear more suitable for diagnostic purposes, allowing use of
      PrP(Sc) as selection target. Peptide aptamers facilitate appropriate
      intracellular expression, targeting and re-routing without losing their binding
      properties to PrP, a requirement for potential therapeutic gene transfer
      experiments in vivo. Elucidation of structural properties of peptide aptamers
      might be used as basis for rational drug design, providing another attractive
      application of peptide aptamers in the search for effective anti-prion
      strategies.

PMID- 19396402
TI  - Stage- and tissue-specific expression of rice OsIsu1 gene encoding a scaffold
      protein for mitochondrial iron-sulfur-cluster biogenesis.
AB  - Isu is a scaffold protein involved in mitochondrial iron-sulfur-cluster
      biogenesis, which affects redox and iron homeostasis in human and yeast cells. A
      BLASTP search identified two putative Isu genes in rice, and we designated one of
      them as OsIsu1. When expressed in onion epidermal cells, OsIsu1::GFP was
      localized to the mitochondria. Northern analysis showed that OsIsu1 was down
      regulated in iron-deficient rice root. OsIsu1 promoter-GUS was introduced into
      Arabidopsis thaliana and histochemical GUS-staining showed that OsIsu1 expression
      was regulated in a stage- and tissue-specific manner. OsIsu1 was expressed
      ectopically in Arabidopsis under the control of the CaMV35S promoter, which
      increased weight of plants.

PMID- 19396401
TI  - Do children and adults differ in survival from medulloblastoma? A study from the
      SEER registry.
AB  - Studies investigating whether adults have diminished survival from
      medulloblastoma (MB) compared with children have yielded conflicting results. We
      sought to determine in a population-based registry whether adults and children
      with MB differ in survival, and to examine whether dissimilar use of chemotherapy
      might contribute to any disparity. 1,226 MB subjects were identified using the
      Surveillance Epidemiology and End Results (SEER-9) registry (1973-2002) and
      survival analysis performed. MB was defined strictly to exclude non-cerebellar
      primitive neuro-ectodermal tumors. Patients were stratified by age at diagnosis:
      <3 years (infants), 3-17 years (children) and >or=18 years (adults). Because the
      SEER-9 registry lacks treatment data, a subset of 142 patients were identified
      using the San Francisco-Oakland SEER registry (1988-2003) and additional analyses
      performed. There was no significant difference in survival between children and
      adults with MB in either the SEER-9 (P = 0.17) or SFO (P = 0.89) cohorts but
      infants fared worse compared to both children (P < 0.01) and adults (P < 0.01).
      In the SFO sample, children and adults who received chemotherapy plus radiation
      therapy (XRT) did not differ in survival. Among patients treated with XRT alone,
      children showed increased survival (P = 0.04) compared with adults. Children and
      adults with MB do not differ with respect to overall survival, yet infants fare
      significantly worse. For children and adults with MB treated with both XRT and
      chemotherapy, we could not demonstrate a survival difference. Similar outcomes
      between adult and childhood MB may justify inclusion of adults in pediatric
      cooperative trials for MB.

PMID- 19396403
TI  - Application of anodic stripping voltammetry for zinc, copper, and cadmium
      quantification in the aqueous humor: implications of pseudoexfoliation syndrome.
AB  - Anodic stripping voltammetric (ASV) procedure, using mercury film electrode, was
      optimized and applied to determine the concentrations of zinc, cadmium, and
      copper in the aqueous humor. Concentration levels as low as 1 ppb of the test
      metals was possible to be detected using short electrolysis times (120 s) and
      microquantities of aqueous humor (up to 35 MUL). As a first application of the
      voltammetric analysis of trace metals in the aqueous humor, the role of the three
      selected trace elements in the pseudoexfoliation (PEX) syndrome was examined.
      Samples from aqueous humor were collected during cataract extraction from
      patients with and without PEX. The zinc and copper concentration levels in the
      aqueous humor did not show statistically significant difference in the study and
      control group. Cadmium was detected in a small number of samples, without however
      statistical differences between the two groups. ASV proved to be a highly precise
      and sensitive tool for the quantification of heavy metal ions in aqueous humor.
      Further studies may lead to useful conclusions for the role of zinc, copper, or
      cadmium in PEX syndrome.

PMID- 19396404
TI  - Effects of dietary zinc and L-arginine supplementation on total antioxidants
      capacity, lipid peroxidation, nitric oxide, egg weight, and blood biochemical
      values in Japanese quails.
AB  - The aim of this study was to evaluate effects of dietary zinc and L-arginine
      supplementation on blood total antioxidant capacity (TAC), malondialdehyde (MDA),
      nitric oxide (NO), some blood chemistry parameters, and egg weights of laying
      quails. Three groups of Japanese quails were fed with a diet containing L
      arginine (5 mg/kg), zinc (60 mg/kg), and normal basal diet (control) for 30 days.
      TAC, lipid peroxidation, and biochemical analysis were performed in the blood of
      animals. L-Arginine and zinc supplementation improved TAC and reduced MDA
      concentrations compared to the control (P<0.05). In comparison to the control,
      blood NO concentrations were increased by Larginine (P<0.01) and zinc treatment
      (P<0.05). Both zinc (P<0.001) and L-arginine (P< 0.01) supplementation
      significantly increased egg weight in laying quails. Some of the blood chemistry
      parameters were also altered by the treatment of L-arginine and zinc
      supplementation. No difference was found in blood albumin and creatinine levels
      among the groups. Blood glucose (P=0.833) and total protein (P=0.264) levels in
      control and Larginine-treated groups were found to be similar. Glucose and total
      protein levels were decreased in zinc-supplemented animals compared to the
      control and L-arginine groups (P< 0.05). No difference was found in triglyceride
      levels between control and zinc-applied groups (P=0.197). However, L-arginine
      treatment reduced the blood triglyceride levels compared to the control (P<0.05).
      In conclusion, L-arginine and zinc supplementation could be beneficial and
      effective for decreasing oxidative stress, boosting antioxidant capacity, and
      improving egg weight in the blood of the animals.

PMID- 19396405
TI  - Effects of N-acetylcysteine, deferoxamine and selenium on doxorubicin-induced
      hepatotoxicity.
AB  - The aims of our study were to evaluate the antioxidant defence mechanisms of
      liver tissue challenged by doxorubucin (DOX) and to compare the possible
      protective effects of N-acetylcysteine (NAC) (n=10), deferoxamine (DOF) (n=10),
      DOF+NAC (n= 10) and selenium (n=9) on doxorubicin-induced hepatotoxicity. Fifty
      six male rats (Mean weight = 250 +/- 50 g) randomly divided into five groups.
      Animals in study groups were pretreated with a single dose of Dox, which was
      administered intravenously. Control group (n=7) was treated with intravenous
      saline injection. Selenium was given intraperitoneally. Blood and urine samples
      were collected before sacrifice. Liver tissue samples were collected and tissue
      superoxide dismutase (SOD), glutathione peroxidase (GSH-px), CAT activity, MDA,
      Zn, iron and copper were determined. DFO decreased lipid peroxidation
      significantly. DFO and NAC decreased CAT activity significantly. Antioxidant
      regimes increase SOD activities significantly. DOF and NAC increase GSH-px
      activities and copper levels significantly. Beneficial effect of selenium seems
      to result from its stimulation of SOD but not to GSH-px. It has been found that
      DOF, NAC and selenium have protective effects on Dox-induced hepatocellular
      damage. DOF+NAC did not result additional benefit.

PMID- 19396406
TI  - Spectroscopic behavior and biological activity of K3[VO(O2)2CO3]?H2O.
AB  - The potassium salt of the carbonato oxodiperoxovanadate(V) complex, obtained by a
      known synthetic procedure, was thoroughly characterized by infrared, Raman, and
      electronic spectroscopy. The bioactivity of the complex on the cell proliferation
      was tested on osteoblast-like cells (MC3T3E1 osteoblastic mouse calvaria-derived
      cells and UMR106 rat osteosarcoma-derived cells) in culture. At low doses, the
      complex is more toxic for the nontransformed osteoblasts than for the tumoral
      ones, whereas at higher doses the deleterious effects are similar for both cell
      lines. This peroxo complex seems to be the most toxic compound that has so far
      been tested on osteoblast-like cells in culture.

PMID- 19396407
TI  - The effects of lanthanoid on the structure-function of lactate dehydrogenase from
      mice heart.
AB  - The activity of lactate dehydrogenase (LDH, EC1.1.1.27) is often changed upon
      inflammatory responses in animals. Lanthanoid (Ln) was shown to provoke various
      inflammatory responses both in rats and mice; however, the molecular mechanism by
      which Ln3+ exert its toxicity has not been completely understood, especially that
      we know little about the mechanism of the interaction between Ln with 4f electron
      shell and alternation valence and LDH. In this report, we investigated the
      mechanisms of LaCl3, CeCl3, and NdCl3 on LDH activity in vivo and in vitro. Our
      results showed that La3+, Ce3+, and Nd3+ could significantly activate LDH in vivo
      and in vitro; the order of activation was Ce3+>Nd3+> La3+>control. The affinity
      of LDH for Ce3+ was higher than Nd3+ and La3+; the saturated binding sites for
      Ce3+ on the LDH protein were 1.2 and for La3+ and Nd3+ 1.55. Ln3+ caused the
      reduction of exposure degree of cysteine or tryptophan/tyrosine of LDH, the
      increase of space resistance, and the enhancement of alpha-helix in secondary
      structure of LDH, which was greatest in Ce3+ treatment, medium in Nd3+ treatment,
      and least in La3+ treatment. It implied that the changes of structure-function on
      LDH caused by Ln3+ were closely related to the characteristics of 4f electron
      shell and alternation valence in Ln.

PMID- 19396408
TI  - Effects of selenium and L-carnitine on oxidative stress in blood of rat induced
      by 2.45-GHz radiation from wireless devices.
AB  - The levels of blood lipid peroxidation, glutathione peroxidase, reduced
      glutathione, and vitamin C were used to follow the level of oxidative damage
      caused by 2.45 GHz electromagnetic radiation in rats. The possible protective
      effects of selenium and L-carnitine were also tested and compared to untreated
      controls. Thirty male Wistar Albino rats were equally divided into five groups,
      namely Groups A1 and A2: controls and sham controls, respectively; Group B: EMR;
      Group C: EMR + selenium, Group D: EMR + L-carnitine. Groups B-D were exposed to
      2.45 GHz electromagnetic radiation during 60 min/ day for 28 days. The lipid
      peroxidation levels in plasma and erythrocytes were significantly higher in group
      B than in groups A1 and A2 (p<0.05), although the reduced glutathione and
      glutathione peroxidase values were slightly lower in erythrocytes of group B
      compared to groups A1 and A2. The plasma lipid peroxidation level in group A2 was
      significantly lower than in group B (p<0.05). Erythrocyte reduced glutathione
      levels (p<0.01) in group B; erythrocyte glutathione peroxidase activity in group
      A2 (p<0.05), group B (p<0.001), and group C (p<0.05) were found to be lower than
      in group D. In conclusion, 2.45 GHz electromagnetic radiation caused oxidative
      stress in blood of rat. L-carnitine seems to have protective effects on the 2.45
      GHz-induced blood toxicity by inhibiting free radical supporting antioxidant
      redox system although selenium has no effect on the investigated values.

PMID- 19396409
TI  - Effect of trimetazidine on quality of life in elderly patients with ischemic
      dilated cardiomyopathy.
AB  - INTRODUCTION: Elderly patients have an increased incidence of ischemic dilated
      cardiomyopathy, often related to diffuse coronary artery disease. Data have been
      cumulated to suggest that trimetazidine improves myocardial ischemia in patients
      with ischemic heart disease and improves left ventricular function in elderly
      patients with ischemic cardiomyopathy. The purpose of the present study was to
      assess the effects of trimetazidine in addition to standard cardiovascular
      therapy on left ventricular function and quality of life (QOL) parameters in
      elderly patients with ischemic heart disease and reduced left ventricular
      function. METHODS: Patients were randomized to receive either trimetazidine
      (twice daily) or placebo (twice daily) in addition to standard therapy, and were
      evaluated at baseline and after 6 months. RESULTS: Forty-seven patients completed
      the study (40 male, seven female; mean [+/-SD] age 78+/-3.4 years). Demographic
      data were comparable between the two groups with respect to sex, age, and race.
      At 6 months there was a significant improvement in the number of angina episodes
      per week in the trimetazidine group (-2.3+/-1, P=0.023). The overall assessment
      of QOL by a visual analog scale showed an improvement in patients randomized to
      trimetazidine at 6 months (from 4.1+/-0.6 to 6.4+/-0.8, P<0.01) and no changes in
      patients randomized to placebo (from 4.3+/-0.7 to 4.2+/-0.9, P>0.05). Physical
      QOL, evaluated by a MacNew Quality of Life After Myocardial Infarction
      questionnaire (MacNewQLMI), improved in patients randomized to trimetazidine but
      not in those allocated to placebo (32%+/-5% vs. -1%+/-3%, P<0.01). Similar
      results were obtained on social QOL evaluated by MacNewQLMI with trimetazidine
      compared with placebo (39%+/-4% vs. -2%+/-5%, P<0.01). CONCLUSION: In elderly
      patients with ischemic heart disease and reduced ventricular function,
      trimetazidine improves clinical condition and QOL.

PMID- 19396411
TI  - [Recurrent tonsillopharyngitis associated with Burkholderia cenocepacia : two
      case reports].
AB  - The Burkholderia cepacia complex comprises bacteria typically responsible for
      respiratory infections in immunocompromised and cystic fibrosis patients.
      However, these bacteria are rarely associated with infections in immunocompetent
      patients. In the presented case reports of two nonhospitalized immunocompetent
      female patients who underwent tonsillectomy as the ultimate therapy for recurrent
      tonsillopharyngitis, Burkholderia cenocepacia were demonstrated in the surgically
      removed tonsils. The clinical, histological, and microbiological findings of both
      cases are presented. The etiological relevance and the probable success of
      antibiotic treatment versus surgical measures are discussed.

PMID- 19396410
TI  - [Meniere's disease : evidence and controversies].
AB  - Meniere's disease is recognized as the idiopathic form of recurrent inner ear
      disease with the trias of hearing loss, tinnitus and vertigo with aural fullness
      and Meniere's syndrome as the non-idiopathic form. Subentities with unknown
      pathogenesis are Lermoyez' s syndrome and Tumarkin crises. A common pathogenetic
      factor is the disturbance of endolymphatic and perilymphatic osmotic and
      hydrostatic pressure due to defined etiologies or to idiopathic attacks.
      Etiologies of Meniere's syndrome can be pathologic middle ear pressure, anomalies
      of the vestibular and cochlear aqueducts, round window topography, patency of the
      ductus peruniens and the utriculo-endolymphatic valve. Indications for treatment
      are assessed according to the AAO-HNS guidelines and the neurotological function
      tests and dizziness inventories. Betahistine is recommended as first choice
      medical treatment as on-label or high dosage administration. In case of medical
      treatment failure and if hearing is worth saving, endolymphatic shunt surgery
      (ELS) is the first choice. If deafferentiation of the labyrinth is needed
      vestibular neurectomy (VE) should be performed. Local gentamicine administration
      has good long-term results but macula function can often recover and hearing is
      often deteriorated. Future aspects for the treatment are new experimental results
      with gene transfer to vestibular hair cells.

PMID- 19396412
TI  - [Hematopoietic stem cell transplantation. Indications, foundations and
      perspective].
AB  - The hematopoietic stem cell transplantation (HSCT) has become a standard therapy
      for many inherited and acquired disorders of the bone marrow and immune system.
      Autologous HSCT is mainly done as part of the primary therapy in multiple myeloma
      and as part of relapse therapy in malignant lymphoma. In contrast, allogeneic
      HSCT is predominantly performed in patients with acute leukemias. The selection
      process for allogeneic HSCT takes disease-specific as well as patient-specific
      factors into account. Risk factors which can predict for poor response to
      chemotherapy can now be identified in acute myeloid as well as lymphoid leukemia,
      based on phenotype, cytogenetics, molecular genetics and response to therapy. In
      these patients allogeneic HSCT can improve overall survival from 0-20% to 30-60%.
      New conditioning protocols have now raised the upper age limit for
      transplantation to 70 years. In elderly patients the selection of patients based
      on absence of comorbidities becomes especially important. The increasing number
      of long-term survivors requires knowledge of organ-specific late toxicities
      including secondary malignancies.

PMID- 19396413
TI  - [Current problems of kidney transplantation].
AB  - The long-term problems after kidney transplantation have changed considerably in
      recent years. While formerly immunosuppression and prevention of acute rejection
      were of prime concern, now attention focuses on chronic alterations of the
      transplanted organ and long-term survival of the patients. The transplantation
      procedure itself has evolved into a standardized technique with a high level of
      surgical quality. Problems involving organ preservation and ischemia/reperfusion
      damage also play a role, especially in view of chronic aspects. Monitoring of
      long-term complications should follow a program for the transplanted organ as
      well as a program for the patient. Monitoring kidney function should address the
      organ more precisely than has previously been the case. Serum creatinine level
      and proteinuria alone provide insufficient information and only change long after
      cellular deterioration has begun. Hence it is imperative that new testing methods
      be developed. One possibility is offered by protocol biopsies that allow
      histological and molecular analysis of the kidney at regular intervals. The
      patient programs concentrate on diagnostics and treatment of the cardiovascular
      diseases. Furthermore, the patients must be screened for occurrence of neoplasia.
      There are no prospective studies covering all cardiovascular risk factors after
      kidney transplantation. This pertains particularly to the subject of
      hypertension.

PMID- 19396417
TI  - [Saving psychoanalysis. At any cost?].
AB  - Although long-term psychoanalysis has been criticized due to lacking scientific
      efficacy, a meta-analysis by Leichsenring and Rabung concludes it is even more
      effective than other psychological interventions and follows a dose:response
      relationship (i.e. the longer the better). We reassessed this meta-analysis and
      find that its conclusions are not warranted. First, major parts of them are not
      based on the included randomised clinical trials (11) but on observational
      studies (12), which are known to be subject to investigator bias. The definition
      of long-term psychoanalysis included mainly randomised clinical trials with fewer
      than 50 treatment sessions, which is untypically short for this kind of
      intervention. Comparison groups were misclassified (especially the classification
      "cognitive interventions"). Important disorders were not clearly defined,
      hindering any interpretation of which treatment is to be indicated. Moreover the
      authors did not consider the lack of acceptance and attrition rates, nor did they
      include intention-to-treat data sets. For some of the studies only 45% of samples
      were included in the meta-analysis. We conclude that a few of the included
      randomised clinical trials using psychodynamic short-term interventions truly are
      promising and of high quality; however these do not justify generalizations on
      long-term psychoanalysis, and the presented meta-analysis is clearly biased.

PMID- 19396419
TI  - [Subdiagnostic depression. Are there treatments with clinically relevant
      effects?].
AB  - Minor depression, subsyndromal depression and subthreshold depression are
      frequent conditions in primary care which do not fulfil the criteria of a
      depressive disorder but are associated with functional disability, impairment of
      quality of life, and health care use. This paper reviews studies on the clinical
      evidence of pharmacotherapy, psychotherapy, and interventions to improve primary
      care. In this regard, whether clinical relevance of antidepressant therapies can
      be concluded from differences between placebo and active treatment is critically
      discussed. Due to lacking clinical evidence, aspects of a pragmatic therapeutic
      approach in those patients are presented.

PMID- 19396418
TI  - [Core symptoms of depression. Effectiveness of antidepressant therapy].
AB  - Core symptoms of depression are a combination of psychological and somatic
      symptoms, often associated with psychomotor and cognitive disturbances. The
      diagnostic classifications of depression include the concepts of melancholic,
      endogenous, or severe depression. All subgroups describe severely depressed
      patients suffering from most of the core symptoms of depression. In addition
      these patients exhibit the clinical characteristics of a recurrent unipolar or
      bipolar course, lower placebo response rates, or higher response rates to ECT, to
      antidepressant treatments with dually or mixed modes of action, or to lithium
      augmentation. Higher rates of HPA axis hyperactivity and specific EEG patterns
      may also occur in this patient group. This suggests a broad overlap of patient
      subgroups within the diagnostic classification of depression. Because the
      positive diagnosis of the core symptoms of depression may include clinical
      consequences, it would be useful to integrate all these concepts into the
      upcoming new versions of the diagnostic systems DSM-V and ICD-11.

PMID- 19396420
TI  - Identification of novel QTLs for seedling and adult plant leaf rust resistance in
      a wheat doubled haploid population.
AB  - Pyramiding of genes that confer partial resistance is a method for developing
      wheat (Triticum aestivum L.) cultivars with durable resistance to leaf rust
      caused by Puccinia triticina. In this research, a doubled haploid population
      derived from the cross between the synthetic hexaploid wheat (SHW)
      (xAegilotriticum spp.) line TA4152-60 and the North Dakota breeding line ND495
      was used for identifying genes conferring partial resistance to leaf rust in both
      the adult plant and seedling stages. Five QTLs located on chromosome arms 3AL,
      3BL, 4DL, 5BL and 6BL were associated with adult plant resistance with the latter
      four representing novel leaf rust resistance QTLs. Resistance effects of the 4DL
      QTL were contributed by ND495 and the effects of the other QTLs were contributed
      by the SHW line. The QTL on chromosome arm 3AL had large effects and also
      conferred seedling resistance to leaf rust races MJBJ, TDBG and MFPS. The other
      major QTL, which was on chromosome arm 3BL, conferred seedling resistance to race
      MFPS and was involved in a significant interaction with a locus on chromosome arm
      5DS. The QTLs and the associated molecular markers identified in this research
      can be used to develop wheat cultivars with potentially durable leaf rust
      resistance.

PMID- 19396421
TI  - Identification of QTL affecting seed mineral concentrations and content in the
      model legume Medicago truncatula.
AB  - Increasing the amount of bioavailable micronutrients such as iron and zinc in
      plant foods for human consumption is an international goal, intended especially
      for developing countries where micronutrient deficiencies are an ongoing health
      risk. Legume seeds have the potential to provide the essential nutrients required
      by humans, but concentrations of several minerals are low when compared to other
      foods. In order to increase seed mineral concentrations, it is important to
      understand the genes and processes involved in mineral distribution within the
      plant. The main objectives of this study were to use a Medicago truncatula
      recombinant inbred population (Jemalong-6 x DZA 315.16) to determine loci
      governing seed mineral concentrations, seed mineral content, and average seed
      weight, and to use these loci to propose candidate genes whose expression might
      contribute to these traits. Ninety-three lines in 2004 and 169 lines in 2006 were
      grown for seed harvest and subsequent analysis of seed Ca, Cu, Fe, K, Mg, Mn, P,
      and Zn concentrations and content. Quantitative trait loci (QTL) cartographer was
      used to identify QTL using composite interval mapping (CIM). CIM identified 46
      QTL for seed mineral concentration, 26 for seed mineral content, and 3 for
      average seed weight. At least one QTL was detected for each mineral trait, and
      colocation of QTL for several minerals was found in both years. Results comparing
      seed weight with seed mineral concentration and content QTL demonstrate that seed
      size can be an important determinant of seed mineral concentration. The
      identification, in this model legume, of transgressive segregation for nearly all
      the minerals suggests that allelic recombination of relevant mineral-related
      genes in agronomic legumes could be a successful strategy to increase seed
      mineral concentrations above current levels.

PMID- 19396422
TI  - Prevention of diabetes by a hydrolysed casein-based diet in diabetes-prone
      BioBreeding rats does not involve restoration of the defective natural regulatory
      T cell function.

PMID- 19396423
TI  - Masked nocturnal hypertension--a novel marker of risk in type 2 diabetes.
AB  - AIMS/HYPOTHESIS: This study was designed to evaluate the prevalence of masked
      nocturnal hypertension (MNHT) and its impact on arterial stiffness and central
      blood pressure in patients with type 2 diabetes. METHODS: Middle-aged patients (n
      = 414) with type 2 diabetes underwent clinic and ambulatory BP measurements and
      applanation tonometry. RESULTS: MNHT (clinic BP < 130/80 mmHg and night-time BP >
      or = 120/70 mmHg) was found in 7.2% of patients (n = 30). Compared with patients
      with both clinical and nocturnal normotension (n = 70), patients with MNHT had
      higher aortic pulse wave velocity (PWV) (10.2 +/- 1.8 m/s vs 9.4 +/- 1.7 m/s; p =
      0.03) and higher central BP (117.6 +/- 13.9/74.0 +/- 9.1 mmHg vs 110.4 +/-
      16.4/69.7 +/- 9.6 mmHg, p = 0.04). In patients with clinical normotension, night
      time systolic BP correlated significantly with PWV. CONCLUSIONS/INTERPRETATION:
      Thirty per cent of patients with clinical normotension had nocturnal
      hypertension. This was accompanied by increased arterial stiffness and higher
      central BP. We conclude that in clinically normotensive patients with type 2
      diabetes, ambulatory BP measurement may help clinicians to identify patients with
      increased cardiovascular risk.

PMID- 19396424
TI  - Glycaemic impact of patient-led use of sensor-guided pump therapy in type 1
      diabetes: a randomised controlled trial.
AB  - AIMS/HYPOTHESIS: The objective of this study was to assess the impact of patient
      led sensor-guided pump management on glycaemic control, and compare the effect
      with that of standard insulin pump therapy. METHODS: An open multicentre parallel
      randomised controlled trial was conducted at five tertiary diabetes centres.
      Participants aged 13.0-40.0 years with well-controlled type 1 diabetes were
      randomised 1:1 to either study group for 3 months. Randomisation was carried out
      using a central computer-generated schedule. Participants in the intervention
      group used sensor-guided pump management; no instructive guidelines in
      interpreting real-time data were provided ('patient-led' use). Participants in
      the control group continued their original insulin pump regimen. Continuous
      glucose monitoring (CGM) and HbA(1c) level were used to assess outcomes. The
      primary outcome was the difference in the proportion of time in the target
      glycaemic range during the 3 month study period (derived from CGM, target range 4
      10 mmol/l). Secondary outcomes were difference in HbA(1c), time in hypoglycaemic
      (< or =3.9 mmol/l) and hyperglycaemic (> or =10.1 mmol/l) ranges and glycaemic
      variability. RESULTS: Sixty-two participants were recruited and randomised; 5/31
      and 2/31 withdrew from intervention and control groups, respectively, leaving
      26/31 and 29/31 for the intention-to-treat analyses. When adjusted for baseline
      values, the mean end-of-study HbA(1c) was 0.43% lower in the intervention group
      compared with the control group (95% CI 0.19 to 0.75%; p = 0.009). No difference
      was observed in CGM-derived time in target (measured difference 1.72; 95% CI 
      5.37 to 8.81), hypoglycaemic (0.54; 95% CI -3.48 to 4.55) or hyperglycaemic (
      2.18; 95% CI -10.0 to 5.69) range or in glycaemic variability (-0.29; 95% CI 
      0.34 to 0.28). Within the intervention group, HbA(1c) was 0.51% lower in
      participants with sensor use > or =70% compared with participants with sensor use
      <70% (95% CI -0.98 to -0.04, p = 0.04). Five episodes of device malfunction
      occurred. CONCLUSIONS/INTERPRETATION: Individuals established on insulin pump
      therapy can employ sensor-guided pump management to improve glycaemic control. An
      apparent dose-dependent effect of sensor usage was noted; however, frequent use
      of this technology (> or =70%) was not universally acceptable. TRIAL
      REGISTRATION: ACTRN12606000049572

PMID- 19396425
TI  - Are substrate use during exercise and mitochondrial respiratory capacity
      decreased in arm and leg muscle in type 2 diabetes?
AB  - AIM/HYPOTHESIS: The aim of the study was to investigate mitochondrial function,
      fibre type distribution and substrate oxidation in arm and leg muscle during
      exercise in patients with type 2 diabetes and in obese and lean controls.
      METHODS: Indirect calorimetry was used to calculate fat and carbohydrate
      oxidation during both progressive arm-cranking and leg-cycling exercises. Muscle
      biopsies from arm and leg were obtained. Fibre type, as well as O(2) flux
      capacity of saponin-permeabilised muscle fibres were measured, the latter by high
      resolution respirometry, in patients with type 2 diabetes, age- and BMI-matched
      obese controls, and age-matched lean controls. RESULTS: Fat oxidation was similar
      in the groups during either arm or leg exercise. During leg exercise at higher
      intensities, but not during arm exercise, carbohydrate oxidation was lower in
      patients with type 2 diabetes compared with the other groups. In patients with
      type 2 diabetes, ADP-stimulated state 3 respiration per mg muscle with parallel
      electron input from complex I+II was lower in m. vastus lateralis compared with
      obese and lean controls, whereas no differences between groups were present in m.
      deltoideus. A higher percentage of type IIX fibres was seen in m. vastus
      lateralis in patients with type 2 diabetes compared with obese and lean controls,
      whereas no difference was found in the deltoid muscle.
      CONCLUSIONS/INTERPRETATION: This study demonstrates similar O(2) flux capacity,
      fibre type distribution and carbohydrate oxidation in arm muscle in the groups
      despite the presence of attenuated values in leg muscle in patients with type 2
      diabetes compared with obese and lean controls.

PMID- 19396426
TI  - Glucose inhibits the insulin-induced activation of the insulin-degrading enzyme
      in HepG2 cells.
AB  - AIMS/HYPOTHESIS: Hepatic insulin degradation decreases in type 2 diabetes.
      Insulin-degrading enzyme (IDE) plays a key role in insulin degradation and its
      gene is located in a diabetes-associated chromosomal region. We hypothesised that
      IDE may be regulated by insulin and/or glucose in a liver cell model. To validate
      the observed regulation of IDE in vivo, we analysed biopsies of human adipose
      tissue during different clamp experiments in men. METHODS: Human hepatoma HepG2
      cells were incubated in normal (1 g/l) or high (4.5 g/l) glucose medium and
      treated with insulin for 24 h. Catalytic activity, mRNA and protein levels of IDE
      were assessed. IDE mRNA levels were measured in biopsies of human subcutaneous
      adipose tissue before and at 240 min of hyperinsulinaemic, euglycaemic and
      hyperglycaemic clamps. RESULTS: In HepG2 cells, insulin increased IDE activity
      under normal glucose conditions with no change in IDE mRNA or protein levels.
      Under conditions of high glucose, insulin increased mRNA levels of IDE without
      changes in IDE activity. Both in normal and high glucose medium, insulin
      increased levels of the catalytically more active 15a IDE isoform compared with
      the 15b isoform. In subcutaneous adipose tissue, IDE mRNA levels were not
      significantly upregulated after euglycaemic or hyperglycaemic clamps.
      CONCLUSIONS/INTERPRETATION: Insulin increases IDE activity in HepG2 cells in
      normal but not in high glucose conditions. This disturbance cannot be explained
      by corresponding alterations in IDE protein levels or IDE splicing. The loss of
      insulin-induced regulation of IDE activity under hyperglycaemia may contribute to
      the reduced insulin extraction and peripheral hyperinsulinaemia in type 2
      diabetes.

PMID- 19396427
TI  - Purinergic P2X7 receptors regulate secretion of interleukin-1 receptor antagonist
      and beta cell function and survival.
AB  - AIMS/HYPOTHESIS: In obesity, beta cells activate compensatory mechanisms to adapt
      to the higher insulin demand. Interleukin-1 receptor antagonist (IL-1Ra) prevents
      obesity-induced hyperglycaemia and is a potent target for the treatment of
      diabetes, but the mechanisms of its secretion and regulation in obesity are
      unknown. In the present study, we hypothesise the regulation of IL-1Ra secretion
      by purinergic P2X(7) receptors in islets. METHODS: Production and regulation of
      P2X(7) were studied in pancreatic sections from lean and obese diabetic patients,
      non-diabetic controls and in isolated islets. IL-1Ra, IL-1beta and insulin
      secretion, glucose tolerance and beta cell mass were studied in P2x7 (also known
      as P2Rx7)-knockout mice. RESULTS: P2X(7) levels were elevated in beta cells of
      obese patients, but downregulated in patients with type 2 diabetes mellitus.
      Elevated glucose and non-esterified fatty acids rapidly activated P2X(7) and IL
      1Ra secretion in human islets, and this was inhibited by P2X(7) blockade. In line
      with our results in vitro, P2x7-knockout mice had a lower capacity to secrete IL
      1Ra. They exhibited severe and rapid hyperglycaemia, glucose intolerance and
      impaired beta cell function in response to a high-fat/high-sucrose diet, were
      unable to compensate by increasing their beta cell mass in response to the diet
      and showed increased beta cell apoptosis. CONCLUSIONS/INTERPRETATION: Our study
      shows a tight correlation of P2X(7) activation, IL-1Ra secretion and regulation
      of beta cell mass and function. The increase in P2X(7) production is one
      mechanism that may explain how beta cells compensate by adapting to the higher
      insulin demand. Disturbances within that system may result in the progression of
      diabetes.

PMID- 19396428
TI  - Surgical release of the internal obturator tendon for the treatment of retro
      trochanteric pain syndrome: a prospective randomized study, with long-term follow
      up.
AB  - Twelve patients with clinical signs of retro-trochanteric pain syndrome were
      randomized to either operative treatment or a control group. Six patients were
      operated on with sectioning of the tendon to the internal obturator near its
      insertion to the trochanter major. There was no significant pain decrease in
      either group at 6 months. However, at 8 years, the decrease in pain was
      significant in the surgical group (P < 0.03) but not in the control group. Three
      patients in the surgical group who needed pain medication with opioids
      preoperatively managed without such drugs at 8 years. Two patients in the
      surgical group were working half time at the 8 year follow-up. Before the start
      of the study the patients had been out of work for 3 and 10 years, respectively.
      At inclusion 4/12 patients had minor degenerative changes at the L3-L5 level as
      seen on computerized tomography or magnetic resonance imaging. At 8 years, the
      corresponding change was found in 7/9 patients (P = 0.025). In conclusion, at 8
      years after surgical release of the internal obturator muscle, the patients had a
      significant decrease in pain compared with the finding at inclusion. The
      corresponding was not found in the control group.

PMID- 19396429
TI  - Pollen discrimination and classification by Fourier transform infrared (FT-IR)
      microspectroscopy and machine learning.
AB  - The discrimination and classification of allergy-relevant pollen was studied for
      the first time by mid-infrared Fourier transform infrared (FT-IR)
      microspectroscopy together with unsupervised and supervised multivariate
      statistical methods. Pollen samples of 11 different taxa were collected, whose
      outdoor air concentration during the flowering time is typically measured by
      aerobiological monitoring networks. Unsupervised hierarchical cluster analysis
      provided valuable information about the reproducibility of FT-IR spectra of the
      same taxon acquired either from one pollen grain in a 25 x 25 microm2 area or
      from a group of grains inside a 100 x 100 microm2 area. As regards the supervised
      learning method, best results were achieved using a K nearest neighbors
      classifier and the leave-one-out cross-validation procedure on the dataset
      composed of single pollen grain spectra (overall accuracy 84%). FT-IR
      microspectroscopy is therefore a reliable method for discrimination and
      classification of allergenic pollen. The limits of its practical application to
      the monitoring performed in the aerobiological stations were also discussed.

PMID- 19396430
TI  - Capillary electrophoresis and column chromatography in biomedical chiral amino
      acid analysis.
AB  - Free amino acids are typically quantified as the sum of their enantiomers,
      because in terrestrial organisms they mainly exist in the left-handed form.
      However, with increasing understanding of the biological significance of right
      handed amino acids interest in enantioselective quantification of amino acids has
      steadily increased. Initially, electrophoretic and chromatographic methods using
      chiral (pseudo)-stationary phases or chiral eluents were applied to the
      separation of amino acid enantiomers. Later, derivatization of amino acids prior
      to chromatography with chiral reagents gained in popularity, because the
      diastereomers formed can be resolved on conventional reversed-phase columns.
      Novel multi-interaction chiral columns turned attention back to direct chiral
      chromatographic methods. Hyphenation to mass spectrometry has increasingly
      replaced optical detection because of superior selectivity, although this has not
      obviated the need for baseline resolution of amino acid enantiomers. Despite the
      progress made, enantioselective separation and quantification of amino acids
      remains an analytical challenge owing to frequently incomplete resolution of all
      naturally occurring enantiomers and insufficient sensitivity for the
      determination of the trace amounts of D-amino acids typically found in biological
      fluids and tissues.

PMID- 19396431
TI  - Amperometric sensing of hydrogen peroxide vapor for security screening.
AB  - Rapid detection of the hydrogen peroxide precursor of peroxide explosives is
      required in numerous security screening applications. We describe a highly
      sensitive and selective amperometric detection of hydrogen peroxide vapor at an
      agarose-coated Prussian-blue (PB) modified thick-film carbon transducer. The
      sensor responds rapidly and reversibly to dynamic changes in the level of the
      peroxide vapor, with no apparent carry over and with a detection limit of 6 ppbv.
      The remarkable selectivity of the PB-based screen-printed electrode towards
      hydrogen peroxide leads to effective discrimination against common beverage
      samples. For example, blind tests have demonstrated the ability to selectively
      and non-invasively identify concealed hydrogen peroxide in drinking cups and
      bottles. The attractive performance of the new microfabricated PB-based
      amperometric peroxide vapor sensor indicates great potential for addressing a
      wide range of security screening and surveillance applications.

PMID- 19396432
TI  - Comparison of differential mobility spectrometry and mass spectrometry for gas
      chromatographic detection of ignitable liquids from fire debris using projected
      difference resolution.
AB  - The significance of forensic arson analysis accelerates the applications of new
      technologies in this area. Based on the previously reported application of
      differential mobility spectrometry (DMS) as a detection method for gas
      chromatography (GC) in arson analysis, the performances of DMS and mass
      spectrometry (MS) were compared using a novel chemometric tool, projected
      difference resolutions (PDRs). The PDR results show that one-way mass spectra
      data exhibit higher resolution than DMS data, while total ion chromatograms from
      GC-DMS show higher resolution than that from GC/MS for differentiating seven
      kinds of ignitable liquids. Combining the information from both chromatography
      and spectra, two-way data always have higher resolution than one-way data for
      these two detection methods, and GC/MS would exhibit better performance than GC
      DMS according to the minimum resolution value. To verify the PDR results, a fuzzy
      rule-building expert system was applied for classifying these seven kinds of
      ignitable liquids from fire debris based on GC-DMS and GC/MS data, respectively.
      The prediction accuracies were consistent with PDR results, which proved that PDR
      is a powerful tool in comparing the performances of different analysis methods
      for pattern recognition.

PMID- 19396433
TI  - Gender bending: auditory cues affect visual judgements of gender in biological
      motion displays.
AB  - The movement of an organism typically provides an observer with information in
      more than one sensory modality. The integration of information modalities reduces
      the likelihood that the observer will be confronted with a scene that is
      perceptually ambiguous. With that in mind, observers were presented with a series
      of point-light walkers each of which varied in the strength of the gender
      information they carried. Presenting those stimuli with auditory walking
      sequences containing ambiguous gender information had no effect on observers'
      ratings of visually perceived gender. When the visual stimuli were paired with
      auditory cues that were unambiguously female, observers' judgments of walker
      gender shifted such that ambiguous walkers were judged to look more female. To
      show that this is a perceptual rather than a cognitive effect, we induced visual
      gender after-effects with and without accompanying female auditory cues. The
      pairing of gender-neutral visual stimuli with unambiguous female auditory cues
      during adaptation elicited male after-effects. These data suggest that biological
      motion processing mechanisms can integrate auditory and visual cues to facilitate
      the extraction of higher-order features like gender. Possible neural substrates
      are discussed.

PMID- 19396434
TI  - Contributions of vision-proprioception interactions to the estimation of time
      varying hand and target locations.
AB  - We investigated the relative importance of vision and proprioception in
      estimating target and hand locations in a dynamic environment. Subjects performed
      a position estimation task in which a target moved horizontally on a screen at a
      constant velocity and then disappeared. They were asked to estimate the position
      of the invisible target under two conditions: passively observing and manually
      tracking. The tracking trials included three visual conditions with a cursor
      representing the hand position: always visible, disappearing simultaneously with
      target disappearance, and always invisible. The target's invisible displacement
      was systematically underestimated during passive observation. In active
      conditions, tracking with the visible cursor significantly decreased the extent
      of underestimation. Tracking of the invisible target became much more accurate
      under this condition and was not affected by cursor disappearance. In a second
      experiment, subjects were asked to judge the position of their unseen hand
      instead of the target during tracking movements. Invisible hand displacements
      were also underestimated when compared with the actual displacement. Continuous
      or brief presentation of the cursor reduced the extent of underestimation. These
      results suggest that vision-proprioception interactions are critical for
      representing exact target-hand spatial relationships, and that such sensorimotor
      representation of hand kinematics serves a cognitive function in predicting
      target position. We propose a hypothesis that the central nervous system can
      utilize information derived from proprioception and/or efference copy for
      sensorimotor prediction of dynamic target and hand positions, but that effective
      use of this information for conscious estimation requires that it be presented in
      a form that corresponds to that used for the estimations.

PMID- 19396435
TI  - Basic mechanisms in pinniped vision.
AB  - Pinnipeds are amphibious mammals. The amphibious lifestyle is challenging for all
      sensory systems including vision, and specific adaptations of the eyes have
      evolved in response to the changed requirements concerning vision in two
      optically very different media, water and air. The present review summarizes the
      information available on pinniped eyes with an emphasis on harbour seal vision
      for which most information is available to date. Recent studies in this species
      have improved the understanding of amphibious vision by reanalysing refraction,
      by studying corneal topography, and by measuring visual acuity as a function of
      ambient luminance. The harbour seal eye can be characterized as an eye that
      balances high resolution, supported by data on ganglion cell density and
      topography, and sensitivity. Furthermore, it was shown that seals have multifocal
      lenses, broad visual Welds, and distinct eye movement abilities. The mechanisms
      described here form the basis for future research on visually guided behaviour.

PMID- 19396436
TI  - Association of the DRD2 and DRD3 polymorphisms with response to pramipexole in
      Parkinson's disease patients.
AB  - OBJECTIVE: To evaluate the impact of the DRD2 TaqIA and DRD3 Ser9Gly
      polymorphisms on the efficacy of pramipexole in treating patients with
      Parkinson's disease (PD). METHODS: Thirty patients with PD prospectively received
      pramipexole 0.25 mg three times daily for 2 months. Unified Parkinson Disease
      Rating Scale (UPDRS) assessments were conducted at baseline and 2 months after
      treatment initiation. Improvement by 20% or more in the total score on the UPDRS
      was considered to indicate responsiveness. The PCR-restriction fragment length
      polymorphism analysis was used to analyze the DRD2 Taq1A and DRD3 Ser9Gly
      genotype. RESULTS: The DRD2 Taq1A allele frequencies were A141.7 (A1) and 58.3%
      (A2), and the DRD3 Ser9Gly allele frequencies were 68.3 (Ser) and 31.7% (Gly).
      When the subjects were grouped by the DRD3 Ser9Gly polymorphism, the response
      rates for pramipexole treatment were significantly higher in the Ser/Ser group
      (60%) than in the group containing the Gly allele (13%). There was a significant
      association between the DRD3 Ser9Gly polymorphism and response rate to
      pramipexole in PD patients (P = 0.024). When the subjects were grouped by the
      DRD2 Taq1A polymorphism, there were no significant differences among the three
      Taq1A genotypes. CONCLUSIONS: DRD3 Ser9Gly polymorphisms are significantly
      associated with the therapeutic efficacy of pramipexole in Chinese patients with
      PD. A large-scale and multi-dose group study in patients with PD is necessary for
      evaluating the impact of the genetic polymorphisms of the dopamine receptor on
      the therapeutic effects of pramipexole.

PMID- 19396437
TI  - Knowledge of developmental pharmacology and modeling approaches should be used to
      avoid useless trials in children.

PMID- 19396438
TI  - High production of 2,3-butanediol from glycerol by Klebsiella pneumoniae G31.
AB  - The microbial production of high amounts of 2,3-butanediol (2,3-BD) from glycerol
      as a sole carbon source by the Bulgarian isolate Klebsiella pneumoniae G31 was
      studied in a series of fed-batch processes. The following conditions were
      evaluated as optimal: micro-aerobic cultivation in modified media, without pH
      control. Beginning at pH 8, 49.2 g/l of 2,3-BD was produced as negligible
      concentrations of by-products were received. The pH is the most important factor
      ruling the 2,3-BD production. Spontaneous pH changes and products formation in
      time were investigated, performing fermentations with non-controlled pH starting
      at different initial pH. In lack of external maintenance, the microorganism
      attempted to control the pH using acetate/2,3-BD alternations of the oxidative
      pathway of glycerol catabolism, which resulted in pH fluctuations. Thus, the
      culture secreted 2,3-BD at unequal portions, either allowing or detaining the
      acetate synthesis. More alkaline initial pH led to enhanced 2,3-BD accumulation
      as a response to the increased amplitudes of the pH variations. When the pH was
      maintained constant, the yield of 2,3-BD was very poor. These cultures remained
      viable only 72 h; whereas, the pH self-controlling cells lived and produced 2,3
      BD up to 280 h. In conclusion, the formation of 2,3-BD is a result of an adaptive
      mechanism of pH self-control, responding to spontaneous pH drops during glycerol
      fermentation.

PMID- 19396439
TI  - CHO-recombinant human growth hormone as a protease sensitive reporter protein.
AB  - Protein-free media are gaining more and more interest in mammalian cell culture
      technology. However, the range of commercially available protein-free media is
      wide, but lack of serum causes the lack of various substances (Keenan et al. in
      Cytotechnology, 50(1-3):49-56, 2006) which must be substituted case by case.
      Details on the composition of protein-free media are often unavailable or
      inaccessible in some cases, and as a consequence, there is an obvious need for
      testing procedures in order to evaluate the various commercialised products for
      their performance. Additionally, negative effects of tryptic meat digests on
      product quality have been reported in the literature (Gu et al. in Biotech Bioeng
      56 (4):353-341, 1997). In the present studies of comparing various protein-free
      media for their suitability in propagation of recombinant CHO cells expressing
      human growth hormone (hGH), we have found somatotropin to be an excellent
      candidate for detection of protease activity. Somatotropin contains protease
      recognition sites for numerous proteases located around amino-acid residues 134
      150. In this study, we demonstrate highly specific cleavage of recombinant hGH
      during batch cultivation. Analysis of the digested molecule was then performed by
      convergent methods like SDS-PAGE, HPLC and mass spectroscopy, and the results
      indicate hGH to be an ideal candidate for media and component screening in
      mammalian cell culture.

PMID- 19396440
TI  - Radiation dosimetry and biodistribution of (99m)Tc-ethylene dicysteine
      deoxyglucose in patients with non-small-cell lung cancer.
AB  - PURPOSE: To assess the radiation dosimetry and biodistribution of (99m)Tc-labeled
      ethylene dicysteine deoxyglucose ((99m)Tc-EC-DG) in patients with non-small-cell
      lung cancer (NSCLC). METHODS: Serial whole-body scans were acquired 0, 2, 4, 6
      and 24 h after injection of (99m)Tc-EC-DG (925 MBq) in seven NSCLC patients.
      Radiation dosimetry, blood clearance and SPECT imaging of the primary tumor were
      assessed. RESULTS: The critical organ was the bladder wall, with average
      radiation absorbed dose over all seven patients of 2.47x10(-2) mGy/MBq. The
      average effective dose equivalent and effective dose were 6.20x10(-3) mSv/MBq
      (6.89 mSv/1,110 MBq) and 5.90x10(-3) mSv/MBq (6.54 mSv/1,110 MBq), respectively.
      The primary tumor was visualized with SPECT in six patients. On final pathology,
      one patient had a granuloma, which did not enhance with (99m)Tc-EC-DG.
      CONCLUSION: (99m)Tc-EC-DG has acceptable dosimetric and biodistribution
      properties as a diagnostic tumor-imaging agent. Future studies are planned to
      evaluate its diagnostic potential.

PMID- 19396441
TI  - Four-strand hamstring tendon autograft versus LARS artificial ligament for
      anterior cruciate ligament reconstruction.
AB  - This retrospective study compared the results after anterior cruciate ligament
      (ACL) reconstruction using a four-strand hamstring tendon graft (4SHG) versus
      Ligament Advanced Reinforcement System (LARS) artificial ligament in 60 patients
      between January 2003 and July 2004 with a minimum four-year follow-up. The KT
      1000 examination, the International Knee Documentation Committee (IKDC) scoring
      systems and Lysholm knee scoring scale were used to evaluate the clinical
      results. The mean side-to-side difference was 2.4 +/- 0.5 mm and 1.2 +/- 0.3 mm
      in the 4SHG group and LARS group, respectively (P = 0.013). Although other
      results of ACL reconstruction, measured by IKDC evaluation, Lysholm scores and
      Tegner scores, showed using a LARS graft clinically tended to be superior to
      using a 4SHG, there were no significant differences calculated. Our results
      suggest that four years after ACL reconstruction using a LARS ligament or 4SHG
      dramatically improves the function outcome, while the patients in the LARS group
      displayed a higher knee stability than those in the 4SHG group.

PMID- 19396442
TI  - [Virilizing adrenal ganglioneuroma : A rare differential diagnosis in
      testosterone secreting adrenal tumours].
AB  - Testosterone secreting tumours of the adrenal glands are usually adrenal
      carcinomas or adenomas. Here we report the rare case of an adrenal ganglioneuroma
      with ectopic Leydig cells, a so-called virilizing adrenal ganglioneuroma.
      Clinically it is characterized by symptoms of virilization, histologically by the
      occurrence of a population of eosinophilic cells. In the absence of crystalloids
      of Reinke this cell population can be identified as Leydig cells based on
      positive immunohistochemical staining of inhibin and calretinin.

PMID- 19396443
TI  - PTR1-dependent synthesis of tetrahydrobiopterin contributes to oxidant
      susceptibility in the trypanosomatid protozoan parasite Leishmania major.
AB  - Leishmania must survive oxidative stress, but lack many classical antioxidant
      enzymes and rely heavily on trypanothione-dependent pathways. We used forward
      genetic screens to recover loci mediating oxidant resistance via overexpression
      in Leishmania major, which identified pteridine reductase 1 (PTR1). Comparisons
      of isogenic lines showed ptr1 (-) null mutants were 18-fold more sensitive to
      H(2)O(2) than PTR1-overproducing lines, and significant three- to fivefold
      differences were seen with a broad panel of oxidant-inducing agents. The
      toxicities of simple nitric oxide generators and other drug classes (except
      antifolates) were unaffected by PTR1 levels. H(2)O(2) susceptibility could be
      modulated by exogenous biopterin but not folate, in a PTR1- but not dihydrofolate
      reductase-dependent manner, implicating H(4)B metabolism specifically. Neither
      H(2)O(2) consumption nor the level of intracellular oxidative stress was affected
      by PTR1 levels. Coupled with the fact that reduced pteridines are at least 100
      fold less abundant than cellular thiols, these data argue strongly that reduced
      pteridines act through a mechanism other than scavenging. The ability of
      unconjugated pteridines to counter oxidative stress has implications to
      infectivity and response to chemotherapy. Since the intracellular pteridine
      levels of Leishmania can be readily manipulated, these organisms offer a powerful
      setting for the dissection of pteridine-dependent oxidant susceptibility in
      higher eukaryotes.

PMID- 19396444
TI  - High-resolution MR imaging of periarterial edema associated with biological
      inflammation in spontaneous carotid dissection.
AB  - It has been suggested that spontaneous cervical carotid artery dissection (sCAD)
      may result from arterial inflammation. Periarterial edema (PAE), occasionally
      described in the vicinity of the mural hematoma in patients with sCAD, may
      support this hypothesis. Using cervical high-resolution magnetic resonance
      imaging, three readers, blinded to the mechanism of carotid artery dissection,
      searched for PAE, defined as periarterial T2-hyperintensity and T1-hypointensity,
      in 29 consecutive CAD patients categorized as spontaneous CAD (sCAD, n = 18) or
      traumatic CAD (tCAD, n = 11; i.e., major head or neck trauma within 2 weeks
      before the clinical onset). The relationships between PAE, inflammatory
      biological markers, history of infection and CAD mechanism were explored.
      Multiple CADs (n = 8) were found only in sCAD patients. Compared with tCAD,
      patients with sCAD were more likely to have a recent history of infection (OR =
      12.5 [(95%)CI = 1.3-119], p = 0.03), PAE (83% vs. 27%; OR = 13.3 [(95%)CI = 2.2
      82.0], p = 0.005) and to have elevated CRP (OR = 6.1 [(95%)CI = 1.2-32.1], p =
      0.0002) or ESR (OR = 8.8 [(95%)CI = 1.5-50.1], p = 0.002) values. Interobserver
      agreement was 0.84 or higher for PAE identification. sCAD was associated with PAE
      and biological inflammation. Our results support the hypothesis of an underlying
      arterial inflammation in sCAD.

PMID- 19396445
TI  - Parotid incidentaloma identified by combined 18F-fluorodeoxyglucose whole-body
      positron emission tomography and computed tomography: findings at grayscale and
      power Doppler ultrasonography and ultrasound-guided fine-needle aspiration biopsy
      or core-needle biopsy.
AB  - Twelve parotid incidentalomas in 10 consecutive subjects (nine with a known
      malignancy elsewhere and one presumptively healthy subject) identified by
      combined 18F-fluorodeoxyglucose whole-body positron emission tomography and
      computed tomography (18F-FDG PET/CT) were investigated, with the aim of
      calculating maximum standardized uptake value (SUV(max)) of each FDG-avid focus,
      and identifying corresponding sonographic and pathologic findings. The results of
      ultrasound-guided fine-needle aspiration biopsy (FNAB) (n = 9) and core-needle
      biopsy (CNB) (n = 3) were Warthin tumor in 10 cases, and pleomorphic adenoma and
      chronic inflammation in one each. SUV(max) was 7.0-21.0 g/mL (average 13.7 g/mL)
      for Warthin tumor, 6.8 g/mL for pleomorphic adenoma, and 7.3 g/mL for chronic
      inflammation. Each FDG-avid focus corresponded to ovoid (n = 11) or lobulated (n
      = 1) hypoechoic mass on grayscale ultrasonography (US) and hypervascular mass,
      except one with chronic inflammation, on power Doppler (PD) US. Parotid
      incidentaloma identified by 18F-FDG PET/CT during workup of various malignancies
      elsewhere does not necessarily signify primary or metastatic malignancy, but
      indicates a high likelihood of benign lesions, particularly Warthin tumor. Such
      lesions should be evaluated thoroughly by US and ultrasound-guided FNAB or CNB if
      parotid disease would change the patient's treatment plan.

PMID- 19396446
TI  - Longitudinal changes in rheumatoid arthritis after rituximab administration
      assessed by quantitative and dynamic contrast-enhanced 3-T MR imaging:
      preliminary findings.
AB  - We retrospectively assessed the longitudinal changes of rheumatoid arthritis
      under rituximab therapy by use of quantitative and dynamic contrast-enhanced 3-T
      magnetic resonance (MR) imaging of the metacarpophalangeal joints of 10 patients
      at baseline and 26 weeks (n = 10). Additional studies were available at 12 weeks
      (n = 9) and at 52 weeks (n = 5). Clinical activity was assessed by use of the 28
      joint disease activity score (DAS28). MR imaging was used to assess volumes of
      synovial enhancement, osseous enhancement, and erosions and early rapid
      enhancement. DAS28 and serum C-reactive protein trended down over time and were
      significantly lower at 26 weeks. Volume of synovial enhancement and early rapid
      enhancement showed a significant minimum at 26 weeks and increased thereafter.
      The erythrocyte sedimentation rate paralleled these two trends. Osseous
      enhancement did not significantly change over time. Erosions showed a significant
      progression. Trends of DAS28 and erosions were significantly different (P =
      0.0075). In conclusion, our preliminary results suggest that rituximab is
      associated with a decrease of the inflammatory activity of synovitis with a
      minimum at 26 weeks and increasing activity thereafter suggesting recurrence. Our
      results further suggest subclinical progression of erosions with an inverse
      relationship to decreasing disease activity scores. Further studies are needed to
      confirm these results.

PMID- 19396447
TI  - [Topical inhibition of angiogenesis at the cornea. Safety and efficacy].
AB  - BACKGROUND: The efficacy and safety of novel topical inhibitors of corneal
      neovascularisation will be discussed. METHODS: A literature review after a PUBMED
      search and own clinical and experimental results are presented. RESULTS: The off
      label use of Avastin eye drops and GS101 eye drops against insulin receptor
      substrate (IRS)-1, which have been tested in phase II trial, both seem to be
      relatively efficient and safe ways to inhibit progressive corneal
      neovascularisation. Other VEGF antagonists, such as ranibizumab and pegaptanib
      eye drops also inhibit corneal neovascularisation. CONCLUSIONS: Avastin and GS101
      eye drops are the first specific angiogenesis inhibitors for topical inhibition
      of corneal angiogenesis available for clinical use.

PMID- 19396448
TI  - [Bevacizumab goes anterior: antiangiogenic therapy at cornea and conjunctiva].

PMID- 19396449
TI  - Slow-transit constipation in children: our experience.
AB  - Constipation is a common problem in children, with childhood prevalence estimated
      at between 1 and 30%. It accounts for a significant percentage of referrals to
      paediatricians and paediatric gastroenterologists. It commonly runs in families,
      suggesting either an underlying genetic predisposition or common environmental
      factors, such as dietary exposure. The peak age for presentation of constipation
      is shortly after toilet training, when passage of hard stools can cause pain on
      defecation, which then triggers holding-on behaviour in the child. At the time of
      the next call to stool the toddler may try to prevent defecation by contraction
      of the pelvic floor muscles and anal sphincter. Unless the holding-on behaviour
      is quickly corrected by interventions to soften faeces and prevent further pain,
      the constipation can very rapidly become severe and chronic. Until recently, this
      mechanism was thought to be the only significant primary cause of constipation in
      childhood. In this review, we will summarise recent evidence to suggest that
      severe chronic constipation in children may also be due to slowed colonic
      transit.

PMID- 19396450
TI  - Inflammatory myofibroblastic tumor of the liver due to Mycobacterium tuberculosis
      in an immunocompetent girl.
AB  - The case of a 9-year-old girl with a Mycobacterium tuberculosis inflammatory
      myofibroblastic tumor (IMT) of the left lobe of the liver is reported. The tumor
      was surgically excised and had histological features diagnostic of IMT, a
      positive Ziehl-Nielsen staining for acid-fast bacilli and a positive polymerase
      chain reaction for Mycobacterium tuberculosis. Surgical excision of the tumor
      followed by anti-tuberculosis treatment for 9 months resulted in full recovery.
      The patient had no apparent immune disorder, and there was no evidence of
      extrahepatic tuberculosis. These findings make this case exceptional because
      IMTs, due mostly to atypical mycobacteria, have been described only in
      immunocompromised patients.

PMID- 19396451
TI  - Ligasure versus diathermy hemorrhoidectomy under spinal anesthesia or pudendal
      block with ropivacaine: a randomized prospective clinical study with 1-year
      follow-up.
AB  - PURPOSE: We evaluate the safety and efficacy of a spinal anesthesia with
      lidocaine versus a local anesthesia of pudendal block with ropivacaine combined
      with intravenous sedation in the hemorrhoidectomy procedure and also we compared
      the short- and long-term efficacy of conventional diathermy versus Ligasure
      diathermy hemorrhoidectomy. METHODS: Seventy-four patients of grade III or IV
      hemorrhoids were randomized to conventional diathermy hemorrhoidectomy under
      spinal (n = 19) or local anesthesia (n = 18) and Ligasure diathermy
      hemorrhoidectomy under spinal (n = 17) or local anesthesia (n = 20). Time of
      follow-up was 12 months. RESULTS: Patients operated under local anesthesia had
      less pain (p < 0.01), less analgesic requirements (p < 0.001), shorter hospital
      stay (p < 0.01), and less postoperative complications (p < 0.05). A shorter
      operating time (p < 0.001) and less complications at 4 months postoperatively (p
      < 0.05) was observed in the Ligasure group, but differences at 12 months were not
      found. CONCLUSIONS: Hemorrhoidectomy under local anesthesia with pudendal block
      with ropivacaine and sedation reduced postoperative pain, analgesic requirements,
      and postoperative complications, and can be performed as day-case procedure.
      Ligasure diathermy hemorrhoidectomy reduced operating time and was equally
      effective than conventional diathermy in long-term symptom control.

PMID- 19396452
TI  - Liver resection for concomitant colorectal liver metastases and intrahepatic
      cholangiocarcinoma: a rare combination.

PMID- 19396453
TI  - Primary angiosarcoma of the ovary complicated by hemoperitoneum: a case report
      and review of the literature.
AB  - BACKGROUND: Sarcomas of the female genital tract are very rare. A small subset of
      these, primary ovarian angiosarcoma, is even more rare, with only 26 cases
      reported in the literature. Most cases of advanced-stage disease are aggressive
      and demonstrate a poor response to both surgery and chemotherapy with an overall
      poor prognosis. CASE: We present a case of a previously healthy 67-year-old woman
      who presented with abdominal pain and profound anemia. She underwent a full
      staging and optimal debulking that revealed Stage IIIC primary ovarian
      angiosarcoma. The patient died 3 weeks post-operatively secondary to hemorrhage
      from progressive, metastatic tumor sites prior to initiation of chemotherapy.
      CONCLUSION: Primary ovarian angiosarcoma is extremely rare, often presenting in
      later stages with nonspecific symptoms. Immunohistochemical staining of
      pathological specimens can aid in the diagnosis. The optimal regimen for adjuvant
      chemotherapy is unknown, and the prognosis is very poor.

PMID- 19396454
TI  - Distinct acetylation of Trypanosoma cruzi histone H4 during cell cycle, parasite
      differentiation, and after DNA damage.
AB  - Histones of trypanosomes are quite divergent when compared to histones of most
      eukaryotes. Nevertheless, the histone H4 of Trypanosoma cruzi, the protozoan that
      causes Chagas' disease, is acetylated in the N terminus at lysines 4, 10, and 14.
      Here, we investigated the cellular distribution of histone H4 containing each one
      of these posttranslational modifications by using specific antibodies. Histone H4
      acetylated at lysine 4 (H4-K4ac) is found in the entire nuclear space
      preferentially at dense chromatin regions, excluding the nucleolus of replicating
      epimastigote forms of the parasite. In contrast, histone H4 acetylated either at
      K10 or K14 is found at dispersed foci all over the nuclei and at the interface
      between dense and nondense chromatin areas as observed by ultrastructural
      immunocytochemistry. The level of acetylation at K4 decreases in nonreplicating
      forms of the parasites when compared to K10 and K14 acetylations. Antibodies
      recognizing the K14 acetylation strongly labeled cells at G2 and M stages of the
      cell cycle. Besides that, hydroxyurea synchronized parasites show an increased
      acetylation at K4, K10, and K14 after S phase. Moreover, we do not observed
      specific colocalization of K4 modifications with the major sites of RNA
      polymerase II. Upon gamma-irradiation that stops parasite replication until the
      DNA is repaired, dense chromatin disappears and K4 acetylation decreases, while
      K10 and K14 acetylation increase. These results indicate that each lysine
      acetylation has a different role in T. cruzi. While K4 acetylation occurs
      preferentially in proliferating situations and accumulates in packed chromatin,
      K10 and K14 acetylations have a particular distribution probably at the
      boundaries between packed and unpacked chromatin.

PMID- 19396456
TI  - Intravitreal injection of 0.3 ml of SF6 gas for persistent subfoveal fluid after
      scleral buckling for rhegmatogenous retinal detachment.
AB  - PURPOSE: To determine the efficacy of intravitreal injection of sulphur
      hexafluoride (SF6) gas for reducing persistent subfoveal fluid after scleral
      buckling surgery for macula-off rhegmatogenous retinal detachments. METHODS: We
      injected 0.3 ml of SF6 gas into the vitreous cavity of two eyes of two patients
      with persistent macular retinal detachment 3 and 5 months after successful
      scleral buckling. Optical coherence tomography was performed before and after
      surgery. RESULTS: Subfoveal fluid was displaced peripheral to the fovea
      immediately after gas injection and the fluid was absorbed gradually in both
      eyes. CONCLUSIONS: Persistent subfoveal fluid after scleral buckling may be
      treated with intravitreal SF6 gas injection.

PMID- 19396455
TI  - Meiotic localization of Mre11 and Rad50 in wild type, spo11-1, and MRN complex
      mutants of Coprinus cinereus.
AB  - The Mre11-Rad50-Nbs1 (MRN) complex is required for numerous cellular processes
      that involve interactions with DNA double-strand breaks. For the majority of
      these processes, the MRN complex is thought to act as a unit, with each protein
      aiding the activity of the others. We have examined the relationship between
      Mre11 and Rad50 during meiosis in the basidiomycete Coprinus cinereus
      (Coprinopsis cinerea), investigating to what extent activities of Mre11 and Rad50
      are interdependent. We showed that mre11-1 is epistatic to rad50-1 with respect
      to the time of meiotic arrest, indicating that Mre11 activity facilitates the
      diffuse diplotene arrest of rad50 mutants. Anti-Mre11 and anti-Rad50 antibodies
      were used to examine MRN complex localization in a wild-type strain and in spo11,
      mre11, and rad50 mutants. In wild type, numbers of Mre11 and Rad50 foci peaked at
      time points corresponding to leptotene and early zygotene. In the spo11-1 mutant,
      which is defective in meiotic double-strand break formation, foci accumulated
      throughout prophase I. Of seven MRN mutants examined, only two rad50 strains
      exhibited Mre11 and Rad50 foci that localized to chromatin, although Mre11
      protein was found in the cell for all of them. Analysis of predicted mutant
      structures showed that stable localization of Mre11 and Rad50 does not depend
      upon a wild-type hook-proximal coiled coil, but does require the presence of the
      Rad50 ATPase/adenylate cyclase domains. We found that Mre11 and Rad50 were
      interdependent for binding to meiotic chromosomes. However, the majority of foci
      observed apparently contained only one of the two proteins. Independent Mre11 and
      Rad50 foci might indicate disassociation of the complex during meiosis or could
      reflect independent structural roles for the two proteins in meiotic chromatin.

PMID- 19396457
TI  - Bilateral matching of frequency tuning in neural cross-correlators of the owl.
AB  - Sound localization requires comparison between the inputs to the left and right
      ears. One important aspect of this comparison is the differences in arrival time
      to each side, also called interaural time difference (ITD). A prevalent model of
      ITD detection, consisting of delay lines and coincidence-detector neurons, was
      proposed by Jeffress (J Comp Physiol Psychol 41:35-39, 1948). As an extension of
      the Jeffress model, the process of detecting and encoding ITD has been compared
      to an effective cross-correlation between the input signals to the two ears.
      Because the cochlea performs a spectrotemporal decomposition of the input signal,
      this cross-correlation takes place over narrow frequency bands. Since the
      cochlear tonotopy is arranged in series, sounds of different frequencies will
      trigger neural activity with different temporal delays. Thus, the matching of the
      frequency tuning of the left and right inputs to the cross-correlator units
      becomes a 'timing' issue. These properties of auditory transduction gave
      theoretical support to an alternative model of ITD-detection based on a bilateral
      mismatch in frequency tuning, called the 'stereausis' model. Here we first review
      the current literature on the owl's nucleus laminaris, the equivalent to the
      medial superior olive of mammals, which is the site where ITD is detected.
      Subsequently, we use reverse correlation analysis and stimulation with
      uncorrelated sounds to extract the effective monaural inputs to the cross
      correlator neurons. We show that when the left and right inputs to the cross
      correlators are defined in this manner, the computation performed by coincidence
      detector neurons satisfies conditions of cross-correlation theory. We also show
      that the spectra of left and right inputs are matched, which is consistent with
      predictions made by the classic model put forth by Jeffress.

PMID- 19396458
TI  - PTH secretion of "manipulated" parathyroid adenomas.
AB  - PURPOSE: Increased secretion of parathyroid hormone (PTH) and its fragments
      intraoperatively may influence PTH monitoring. The purpose of this study was to
      investigate whether "intended intraoperative manipulation" of parathyroid
      adenomas through mechanical stimulation (through squeezing or manual rubbing)
      would lead to increased PTH excretion. The different PTH fragments that result
      from this kind of manipulation were correlated and analyzed. METHODS: The
      enlarged glands of six consecutive patients who underwent open minimally invasive
      parathyroid exploration were "manipulated" for 30 s as soon as they had been
      identified. Blood samples were drawn before skin incision, at the beginning of
      the manipulation, 30 s, and at 2-, 5-, 10-, and 15-min intervals. Serum levels of
      (1-84)PTH were measured and (7-84)PTH was calculated. RESULTS: An increased PTH
      secretion was documented in four of six "manipulated" single adenomas (mean PTH
      +/- SD 312 +/- 497 pg/ml). The PTH of one patient rose from 343 to 1,747 pg/ml.
      The ratio of (1-84)PTH to (7-84)PTH was 1.3 +/- 0.6 (median +/- SD):1 at
      "baseline" and 1.4 +/- 0.2:1 after manipulation. The coefficient of determination
      (R(2)) for the "baseline values" and for the values after manipulation is R(2) =
      0.9816 and R(2) = 0.9985, respectively. CONCLUSIONS: First, secretion of PTH
      varies widely after manual manipulation of adenomas. Second, PTH fragments
      circulate in the same ratio before and after "manipulation."

PMID- 19396459
TI  - Expression and regulation of hedgehog signaling pathway in pancreatic cancer.
AB  - INTRODUCTION: Pancreatic cancer is an aggressive malignancy with a poor
      prognosis. The overall 5-year survival rate of pancreatic cancer is less than 5%,
      and has not improved significantly for years. Further understanding of the
      molecular carcinogenesis of pancreatic cancer is critical for designing effective
      ways to treat this type of malignancy. METHODS: In this study, we examine
      expression of hedgehog signaling molecules in 54 surgically removed pancreatic
      cancer specimens as well as seven available pancreatic cancer cell lines.
      RESULTS: We find that expression of Ptch is associated with tumor size, tumor
      differentiation, lymph node metastasis, and clinical stages, whereas expression
      of Smo is associated with tumor differentiation and lymph node metastasis. Our
      studies from pancreatic cancer cell lines indicate that targeted inhibition of
      hedgehog signaling by Smo signaling inhibitor KAAD-cyclopamine causes hedgehog
      target gene expression (Gli1) suppression, induces P21 expression and G1 cell
      population, and reduced expression of Cyclin D1 and IGF2. CONCLUSIONS: These
      results indicate that hedgehog signaling activation is a very common event in
      pancreatic cancer and that targeted inhibition of hedgehog signaling may be
      effective in treatment of pancreatic cancer.

PMID- 19396460
TI  - Altered expression of CD44 and DKK1 in the progression of Barrett's esophagus to
      esophageal adenocarcinoma.
AB  - Barrett's esophagus (BE) is an acquired condition in which the normal lining of
      the esophagus is replaced by intestinal metaplastic epithelium. BE can evolve to
      esophageal adenocarcinoma (EAC) through low-grade dysplasia (LGD) and high-grade
      dysplasia (HGD). The only generally accepted marker for increased risk of EAC is
      the presence of HGD, diagnosed on endoscopic biopsies. More specific markers for
      the prediction of EAC risk are needed. A tissue microarray was constructed
      comprising tissue samples from BE, LGD, HGD, and EAC. Marker expression was
      studied by immunohistochemistry using antibodies against CD44, DKK1, CDX2, COX2,
      SOX9, OCT1, E-cadherin, and beta-catenin. Immunostaining was evaluated semi
      quantitatively. CD44 expression decreased in HGD and EAC relative to BE and LGD.
      DKK1 expression increased in HGD and EAC relative to BE and LDG. CDX2 expression
      increased in HGD but decreased in EAC. COX2 expression decreased in EAC, and SOX9
      expression increased only in the upper crypt epithelial cells in HGD. E-cadherin
      expression decreased in EAC. Nuclear beta-catenin was not significantly different
      between BE, LGD, and HGD. Loss of CD44 and gain of DKK1 expression characterizes
      progression from BE and LGD to HGD and EAC, and their altered expression might
      indicate an increased risk for developing an EAC. This observation warrants
      inclusion of these immunohistochemically detectable markers in a study with a
      long patient follow-up.

PMID- 19396461
TI  - What determines the success or failure of intracellular cutaneous parasites?
      Lessons learned from leishmaniasis.
AB  - Most parasitic skin infections are averted by very efficient strategies of
      preventing pathogen invasion. Innate immune cells such as mast cells, macrophages
      and dendritic cells are responsible for detecting parasites and for recruiting
      proinflammatory cells that help to contain and control the pathogen at sites of
      infection. This induces efficient adaptive immunity, which is crucially important
      for parasite control. Using the example of cutaneous leishmaniasis, we highlight
      how the skin utilizes different strategies to prevent skin infection and how
      containment of the infection to the skin site may reduce the harm that otherwise
      may result for the entire organism.

PMID- 19396462
TI  - Clinical practice: diagnosis of childhood tuberculosis.
AB  - Childhood tuberculosis (TB) represents an important part of the disease burden,
      yet its diagnosis remains challenging. This review summarizes the clinical,
      radiological, and bacteriological approaches to diagnose TB infection and disease
      in children. Fever (possibly intermittent or low grade), weight loss or failure
      to thrive, and a persistent cough for >2 weeks are the most important clinical
      signs for pulmonary tuberculosis. Extra-pulmonary TB, which might occur in over
      40% of the patients, can have in addition some specific clinical symptoms or
      signs. Chest radiographs provide important information in many patients and
      advanced imaging can be applied in case of (and should be restricted to)
      inconclusive diagnosis. The Mantoux test is positive in up to 70% of non
      immunocompromised TB patients, whereas HIV co-infection or malnourishment results
      in a lower reactivity. Evidence of an adult TB index case is clue for diagnosis
      of childhood TB in low-endemic countries. Bacteriological confirmation remains
      difficult and is useful for doubtful cases or when drug resistance is suspected.

PMID- 19396463
TI  - Fate of Cryptosporidium parvum and Cryptosporidium hominis oocysts and Giardia
      duodenalis cysts during secondary wastewater treatments.
AB  - This study investigates the fate of Cryptosporidium parvum and C. hominis oocysts
      and Giardia duodenalis cysts at four Irish municipal wastewater treatment plants
      (i.e., Plant A, B, C, and D) that utilize sludge activation or biofilm-coated
      percolating filter systems for secondary wastewater treatment. The fate of these
      pathogens through the sewage treatment processes was determined based on their
      viable transmissive stages, i.e., oocysts for Cryptosporidium and cysts for
      Giardia. Analysis of final effluent indicated that over 97% of viable oocysts and
      cysts were eliminated, except at Plant C, which achieved only 64% of oocyst
      removal. A significant correlation between the removal of oocysts and cysts was
      found at Plants A, B, and D (R = 0.98, P < 0.05). All sewage sludge samples were
      positive for C. parvum and C. hominis, and G. duodenalis, with maximum
      concentrations of 20 oocysts and eight cysts per gram in primary sludge
      indicating the need for further sludge sanitization treatments. This study
      provides evidence that C. parvum and C. hominis oocysts and G. duodenalis cysts
      are present throughout the wastewater processes and in end-products, and can
      enter the aquatic environment with consequent negative implications for public
      health.

PMID- 19396464
TI  - Looking for race in all the wrong places: analyzing the lack of productivity in
      the ongoing debate about race and genetics.
AB  - The ongoing debate about the relationship between race and genetics is more than
      a century old and has yet to be resolved. Recent emphasis on population-based
      patterns in human genetic variation and the implications of those for disease
      susceptibility and drug response have revitalized that long-standing debate. Both
      sides in the debate use the same rhetorical device of treating geographic,
      ancestral, population-specific, and other categories as surrogates for race, but
      otherwise share no evidentiary standards, analytic frameworks, or scientific
      goals that might resolve the debate and result in some productive outcome.
      Setting a common goal of weighing the scientific benefits of using racial and
      other social heuristics with testable estimates of the potential social harms of
      racialization can reduce both the unreflexive use of race and other social
      identities in biological analyses as well as the unreflexive use of racialization
      in social critiques of genetics. Treating social identities used in genetic
      studies as objects for investigation rather than artifacts of participant self
      report or researcher attribution also will reduce the extent to which genetic
      studies that report social identities imply that membership in social categories
      can be defined or predicted using genetic features.

PMID- 19396466
TI  - A review of non-invasive optical-based image analysis systems for continuous
      bioprocess monitoring.
AB  - To observe and control cultivation processes, optical sensors are used
      increasingly. Important variables for controlling such processes are cell count,
      cell size distribution and the morphology of cells. Among turbidity measurement
      methods, imaging procedures are applied for determining these process values. A
      disadvantage of most previously developed imaging procedures is that they are
      only available offline, which requires sampling. On the other hand, available
      imaging inline probes can only deliver a limited number of process values so far.
      This contribution gives an overview of optical procedures for the inline
      determination of cell count, cell size distribution and other variables. In
      particular, by in situ microscopy, an imaging procedure will be described, which
      allows the determination of direct and non-direct cell variables in real time
      without sampling.

PMID- 19396465
TI  - X chromosome inactivation in clinical practice.
AB  - X chromosome inactivation (XCI) is the transcriptional silencing of the majority
      of genes on one of the two X chromosomes in mammalian females. Females are,
      therefore, mosaics for two cell lines, one with the maternal X and one with the
      paternal X as the active chromosome. The relative proportion of the two cell
      lines, the X inactivation pattern, may be analyzed by simple assays in DNA from
      available tissues. This review focuses on medical issues related to XCI in X
      linked disorders, and on the value of X inactivation analysis in clinical
      practice.

PMID- 19396467
TI  - A novel biotransformation process of 4'-demethylepipodophyllotoxin to 4'
      demethylepipodophyllic acid by Bacillus fusiformis CICC 20463, Part II: process
      optimization.
AB  - This work optimized the novel biotransformation process of 4'
      demethylepipodophyllotoxin (DMEP) into 4'-demethylepipodophyllic acid (DMEPA) by
      Bacillus fusiformis CICC 20463. Firstly, the biotransformation process was
      significantly affected by medium composition. 5 g/L of yeast extract and 10 g/L
      of peptone were optimal for DMEPA production (i.e., 2.81 + or - 0.21 mg/L), while
      not beneficial for the cell growth of B. fusiformis. This indicated that the
      biosynthesis of DMEPA was not corresponded well to the cell growth of B.
      fusiformis. 40 g/L of sucrose was optimal for DMEPA production (i.e., 2.94 + or -
      0.17 mg/L), and 3 g/L of NaCl was the best for DMEPA production (i.e., 4.10 + or 
      0.18 mg/L). Secondly, the production of DMEPA was significantly enhanced by the
      control of substrate concentration and culture pH. 100 mg/L of substrate was
      optimal for DMEPA production (i.e., 6.47 + or - 0.35 mg/L), and DMEPA
      concentration was enhanced to 38.78 mg/L by controlling culture pH at 9.0 in the
      stirred-tank bioreactors. The fundamental information obtained in this study
      provides a simple and efficient way to produce DMEPA by biotransformation.

PMID- 19396468
TI  - Fatal pulmonary fibrosis after rituximab administration.
AB  - Idiopathic nephrotic syndrome is the most frequent glomerular disease during
      childhood. Although immunosuppressive agents are usually effective, some severe
      cases remain difficult to treat. We describe a female patient with secondary
      steroid-resistant nephrotic syndrome who no longer responded to conventional
      treatment. Owing to cyclosporine toxicity, rituximab was administered. Three days
      after treatment the patient's clinical condition dramatically worsened and she
      developed acute respiratory distress. Despite all means used to treat her, she
      died 5 weeks after rituximab infusion. A pulmonary biopsy showed extensive
      fibrosis, while the alveolar epithelium was no longer visible.

PMID- 19396469
TI  - Time before isolating cystinotic leukocytes affects reliability of cystine
      determination.

PMID- 19396470
TI  - Part A: Assessing the performance of the COMFA outdoor thermal comfort model on
      subjects performing physical activity.
AB  - This study assessed the performance of the COMFA outdoor thermal comfort model on
      subjects performing moderate to vigorous physical activity. Field tests were
      conducted on 27 subjects performing 30 min of steady-state activity (walking,
      running, and cycling) in an outdoor environment. The predicted COMFA budgets were
      compared to the actual thermal sensation (ATS) votes provided by participants
      during each 5-min interval. The results revealed a normal distribution in the
      subjects' ATS votes, with 82% of votes received in categories 0 (neutral) to +2
      (warm). The ATS votes were significantly dependent upon sex, air temperature,
      short and long-wave radiation, wind speed, and metabolic activity rate. There was
      a significant positive correlation between the ATS and predicted budgets
      (Spearman's rho = 0.574, P < 0.01). However, the predicted budgets did not
      display a normal distribution, and the model produced erroneous estimates of the
      heat and moisture exchange between the human body and the ambient environment in
      6% of the cases.

PMID- 19396471
TI  - Lack of evidence for meteorological effects on infradian dynamics of
      testosterone.
AB  - Climatic factors are known to influence the endocrine system. Previous studies
      have shown that circannual seasonal variations of testosterone might be partly
      explained by changes in air temperature. Whether infradian variations are
      affected by meteorological factors is unknown. To analyze possible effects of
      meteorological parameters on infradian variations of salivary testosterone levels
      in both sexes, daily salivary testosterone levels were measured during 1 month in
      14 men and 17 women. A correlation analysis between hormonal levels and selected
      meteorological parameters was performed. The results indicate that high
      testosterone levels are loosely associated with cold, sunny and dry weather in
      both sexes. However, only the correlations between testosterone and air
      temperature (men) and actual cloudiness (women) were statistically significant (p
      < 0,05). Although some correlations reached the level of statistical
      significance, the effects of selected meteorological parameters on salivary
      testosterone levels remain unclear. Further longer-term studies concentrating on
      air temperature, cloudiness and average relative humidity in relation to the sex
      hormone axis are needed.

PMID- 19396472
TI  - Impairment of mitochondrial beta-oxidation in rats under cold-hypoxic
      environment.
AB  - Mitochondrial beta-oxidation of fatty acid provides a major source of energy in
      mammals. High altitude (HA), characterized by hypobaric hypoxia and low ambient
      temperatures, causes alteration in metabolic homeostasis. Several studies have
      depicted that hypoxic exposure in small mammals causes hypothermia due to
      hypometabolic state. Moreover, cold exposure along with hypoxia reduces hypoxia
      tolerance in animals. The present study investigated the rate of beta-oxidation
      and key enzymes, carnitine palmitoyl transferase-I (CPT-I) and hydroxyacyl CoA
      dehydrogenase (HAD), in rats exposed to cold-hypobaric hypoxic environment. Male
      Sprague Dawley rats (190-220 g) were randomly divided into eight groups (n = 6
      rats in each group): 1 day hypoxia (H1); 7 days hypoxia (H7); 1 day cold (C1); 7
      days cold (C7); 1 day cold-hypoxia (CH1); 7 days cold-hypoxia (CH7) exposed; and
      unexposed control for 1 and 7 days (UC1 and UC7). After exposure, animals were
      anaesthetized with ketamine (50 mg/kg body weight) and xylazine (10 mg/kg body
      weight) intraperitonialy and sacrificed. Mitochondrial CPT-I, HAD, (14)C
      palmitate oxidation in gastrocnemius muscle and liver, and plasma leptin were
      measured. Mitochondrial CPT-I was significantly reduced in muscle and liver in
      CH1 and CH7 as compared to respective controls. HAD activity was significantly
      reduced in H1 and CH7, and in H1, H7, CH1, and CH7 as compared to unexposed
      controls in muscle and liver, respectively. A concomitant decrease in (14)C
      palmitate oxidation was found. Significant reduction in plasma leptin in hypoxia
      and cold-hypoxia suggested hypometabolic state. It can be concluded that ss
      oxidation of fatty acids is reduced in rats exposed to cold-hypoxic environment
      due to the persisting hypometabolic state in cold-hypoxia exposure.

PMID- 19396473
TI  - Continuous non-invasive monitoring of the skin temperature of HSCT recipients.
AB  - GOALS OF WORK: Empirical antibiotic therapy usually started in patients who are
      neutropenic following treatment with cytostatic chemotherapy for a haematological
      malignancy as soon as fever develops to forestall fulminant sepsis. Hence,
      accurate and timely detection of fever is crucial to the successful management of
      infectious complications in these patients. We report an investigation of the
      feasibility and validity of continuous non-invasive body temperature measurement.
      PATIENTS AND METHODS: The feasibility of non-invasive continuous measurement of
      the skin temperature was investigated using the Propaq(R) device in a cohort of
      33 patients receiving an allogeneic HSCT who were all at risk of developing a
      febrile episode. Non-invasive continuous measurement of the skin temperature
      (CST) was compared with a standard episodic axillary temperature measurement
      (EAT) five times daily using a Terumo(R) device. The study period entailed
      monitoring during the 10 or 12 days that profound neutropenia was expected to be
      present. MAIN RESULTS: Measuring the skin temperature continuously and accurately
      by using the Propaq(R) was feasible. The CST correlated well with the EAT
      measurements (Pearson r = 0.782). Compared to EAT, the start of empirical therapy
      could be started 2.5 h earlier when relying on continuous measurements than was
      possible with EAT. CONCLUSION: Continuous skin temperature measurements are
      feasible and valid compared to the conventional temperature measurement and may
      improve the management of infections by earlier detection of fever in neutropenic
      patients.

PMID- 19396474
TI  - Diversity of root-associated fungal endophytes in Rhododendron fortunei in
      subtropical forests of China.
AB  - To investigate the diversity of root endophytes in Rhododendron fortunei, fungal
      strains were isolated from the hair roots of plants from four habitats in
      subtropical forests of China. In total, 220 slow-growing fungal isolates were
      isolated from the hair roots of R. fortunei. The isolates were initially grouped
      into 17 types based on the results of internal transcribed spacer-restriction
      fragment length polymorphism (ITS-RFLP) analysis. ITS sequences were obtained for
      representative isolates from each RFLP type and compared phylogenetically with
      known sequences of ericoid mycorrhizal endophytes and selected ascomycetes or
      basidiomycetes. Based on phylogenetic analysis of the ITS sequences in GenBank,
      15 RFLP types were confirmed as ascomycetes, and two as basidiomycetes; nine of
      these were shown to be ericoid mycorrhizal endophytes in experimental cultures.
      The only common endophytes of R. fortunei were identified as Oidiodendron maius
      at four sites, although the isolation frequency (3-65%) differed sharply
      according to habitat. Phialocephala fortinii strains were isolated most
      abundantly from two habitats which related to the more acidic soil and pine mixed
      forests. A number of less common mycorrhizal RFLP types were isolated from R.
      fortunei at three, two, or one of the sites. Most of these appeared to have
      strong affinities for some unidentified root endophytes from Ericaceae hosts in
      Australian forests. We concluded that the endophyte population isolated from R.
      fortunei is composed mainly of ascomycete, as well as a few basidiomycete
      strains. In addition, one basidiomycete strain was confirmed as a putative
      ericoid mycorrhizal fungus.

PMID- 19396475
TI  - Molecular MR imaging for the evaluation of the effect of dynamic stabilization on
      lumbar intervertebral discs.
AB  - The dynamic stabilization of lumbar spine is a non-fusion stabilization system
      that unloads the disc without the complete loss of motion at the treated motion
      segment. Clinical outcomes are promising but still not definitive, and the long
      term effect on instrumented and adjacent levels is still a matter of discussion.
      Several experiments have been devised in order to gain a better understanding of
      the effect of the device on the intervertebral disc. One of the hypotheses was
      that while instrumented levels are partially relieved from loading, adjacent
      levels suffer from the increased stress. But this has not been proved yet. The
      aim of this study was to investigate the long-term effect of dynamic
      stabilization in vivo, through the quantification of glycosaminoglycans (GAG)
      concentration within instrumented and adjacent levels by means of the delayed
      Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) protocol.
      Ten patients with low back pain, unresponsive to conservative treatment and
      scheduled for Dynesys implantation at one to three lumbar spine levels, underwent
      the dGEMRIC protocol to quantify GAG concentration before and 6 months after
      surgery. Each patient was also evaluated with visual analog scale (VAS),
      Oswestry, Prolo, Modic and Pfirrmann scales, both at pre-surgery and at follow
      up. Six months after implantation, VAS, Prolo and Oswestry scales had improved in
      all patients. Pfirrmann scale could not detect any change, while dGEMRIC data
      already showed a general improvement in the instrumented levels: GAG was
      increased in 61% of the instrumented levels, while 68% of the non-instrumented
      levels showed a decrease in GAG, mainly in the posterior disc portion. In
      particular, seriously GAG-depleted discs seemed to have the greatest benefit from
      the Dynesys implantation, whereas less degenerated discs underwent a GAG
      depletion. dGEMRIC was able to visualize changes in both instrumented and non
      instrumented levels. Our results suggest that the dynamic stabilization of lumbar
      spine is able to stop and partially reverse the disc degeneration, especially in
      seriously degenerated discs, while incrementing the stress on the adjacent
      levels, where it induces a matrix suffering and an early degeneration.

PMID- 19396476
TI  - Intradural extramedullary primary hydatid cyst of the spine in a child: a very
      rare presentation.

PMID- 19396477
TI  - A novel 16p locus associated with BSCL2 hereditary motor neuronopathy: a genetic
      modifier?
AB  - We describe the neurological, electrophysiological, and genetic features of
      autosomal dominant distal hereditary motor neuronopathy (HMN) in a three
      generation Dutch family, including 12 patients with distal muscle weakness and
      atrophy. The severity of disease ranged from disabling muscle weakness to a
      subclinical phenotype. Neurologic exams of nine patients and nerve conduction
      studies (NCS) and myography in five endorsed the variable presentations of HMN in
      this family, including patients with only lower (four), upper (one), or both
      upper and lower extremities involvement (four). Asymmetrical or strictly
      unilateral disease was noted in three patients. Three also showed pyramidal
      features. A genome-wide search combining SNP arrays (250K) with parametric
      linkage analysis identified a novel locus on chromosome 16p (mLOD = 3.28)
      spanning 6 Mb (rs6500882-rs7192086). Direct sequencing excluded mutations in the
      SIMPLE/LITAF gene (mapping to the 16p locus) and identified a pathogenic mutation
      (p.N88S) in BCLS2 (11q12-q14). All 12 affected relatives had the BSCL2 mutation
      and the chromosome 16p haplotype and showed features of motor neuron
      degeneration. One patient had a very mild phenotype with bilateral pes cavus,
      normal concentric needle electromyography but signs of motor neuron involvement
      at electrophysiological muscle scan (EMS). Similar EMS abnormalities in addition
      to abnormal NCS and myography were observed in a clinically unaffected person
      (carrying only the 16p haplotype). These results expand the clinical spectrum of
      HMN and suggest a digenic inheritance of HMN in this family with a BSCL2 mutation
      and a chromosome 16 locus likely contributing to the phenotype.

PMID- 19396478
TI  - Simple and integrated detours: field tests with Columbian ground squirrels.
AB  - An internal representation of space offers flexibility to animals during
      orientation and allows execution of short cuts and detours. We tested the ability
      of 19 free-ranging Columbian ground squirrels (Spermophilus columbianus) to
      perform integrated detours that required travelling under- and aboveground.
      Squirrels were individually tested on their territories (2 tests) and in an arena
      (7 tests). During tests, animals could reach food by running aboveground and then
      through tunnels. For the territory tests, natural tunnels were available. For the
      arena tests, animals used artificial tunnels within a fenced-in part of the
      meadow. For the last arena test, tubes were placed aboveground replicating the
      underground structure. In this test animals were asked to make a simple detour,
      when the full path to the goal was visible. On their territories, 41% of
      squirrels performed detours. All animals reached the food in the arena. When
      choosing an arena detour, squirrels based their decision on the proximity of the
      burrow as well as on whether it led to food. On the last arena test, more
      squirrels performed correct detours on the first attempt compared to other tests.
      The results suggest that ground squirrels can perform simple and integrated
      detours, but animals perform better if the full path is visible.

PMID- 19396479
TI  - Occult injury of the pediatric craniocervical junction.
AB  - The objective of this study is to review the occurrence of occult craniocervical
      junction injury in children. All patients <18 years of age with negative CT of
      the craniocervical junction and subsequent MRI between July 2003 and June 2008
      were included. Age, gender, mechanism of injury, and presence of injuries below
      C2 were tabulated. Of the forty-five patients with negative CT of the
      craniocervical junction, 30 had positive MRI findings at the craniocervical
      junction. Seventeen of the 30 patients fulfilled criteria for significant
      craniocervical junction injury by MRI. Eleven of 17 patients with significant
      craniocervical junction injury were less than 8 years old and 13 of 17 were
      involved in motor vehicle accidents. Six of 12 patients with injury below C2 had
      significant craniocervical injury. Pediatric craniocervical injuries are often
      not evident on radiographic or CT imaging but present on MR imaging.
      Craniocervical injury is most common in younger age groups and is associated with
      motor vehicle accidents and injuries of the lower cervical spine.

PMID- 19396480
TI  - Imaging of blunt pancreatic trauma.
AB  - Blunt pancreatic trauma is an exceedingly rare but life-threatening injury with
      significant mortality. Computed tomography (CT) is commonly employed as the
      initial imaging modality in blunt trauma patients and affords a timely diagnosis
      of pancreatic trauma. The CT findings of pancreatic trauma can be broadly
      categorized as direct signs, such as a pancreatic laceration, which tend to be
      specific but lack sensitivity and indirect signs, such as peripancreatic fluid,
      which tend to be sensitive but lack specificity. In patients with equivocal CT
      findings or ongoing clinical suspicion of pancreatic trauma, magnetic resonance
      cholangiopancreatography (MRCP) may be employed for further evaluation. The
      integrity of the main pancreatic duct is of crucial importance, and though injury
      of the duct may be strongly suggested upon initial CT, MRCP provides clear
      delineation of the duct and any potential injuries. This article aims to review
      and illustrate the CT and magnetic resonance imaging findings of blunt pancreatic
      trauma and delineate the integration of these modalities into the appropriate
      imaging triage of severely injured blunt trauma patients.

PMID- 19396481
TI  - Imaging colorectal trauma using 64-MDCT technology.
AB  - Computed tomography has evolved to become the principal imaging modality in the
      evaluation of colorectal trauma. Direct signs of colorectal trauma are usually
      highly specific but relatively insensitive and, therefore, indirect signs are
      important in the diagnostic of colorectal injuries. In addition, prompt
      recognition of colorectal injury is crucial as even short delays in its diagnosis
      have been shown to significantly increase both morbidity and mortality. All these
      things make colorectal injury a challenge for radiologists. The purpose of this
      review is to describe and analyze the various computed tomography (CT) findings
      of colorectal injuries in both penetrating and blunt trauma using 64-multirow
      detector computed tomography technology, based on our experience in a level I
      trauma center. Additionally, the CT protocol methods specific to colorectal
      injuries are detailed.

PMID- 19396482
TI  - Biological treatment of shrimp production wastewater.
AB  - Over the last few decades, there has been an increase in consumer demand for
      shrimp, which has resulted in its worldwide aquaculture production. In the United
      States, the stringent enforcement of environmental regulations encourages shrimp
      farmers to develop new technologies, such as recirculating raceway systems. This
      is a zero-water exchange system capable of producing high-density shrimp yields.
      The system also produces wastewater characterized by high levels of ammonia,
      nitrate, nitrite, and organic carbon, which make waste management costs
      prohibitive. Shrimp farmers have a great need for a waste management method that
      is effective and economical. One such method is the sequencing batch reactor
      (SBR). A SBR is a variation of the activated sludge biological treatment process.
      This process uses multiple steps in the same reactor to take the place of
      multiple reactors in a conventional treatment system. The SBR accomplishes
      equalization, aeration, and clarification in a timed sequence in a single reactor
      system. This is achieved through reactor operation in sequences, which includes
      fill, react, settle, decant, and idle. A laboratory scale SBR was successfully
      operated using shrimp aquaculture wastewater. The wastewater contained high
      concentrations of carbon and nitrogen. By operating the reactors sequentially,
      namely, aerobic and anoxic modes, nitrification and denitrification were achieved
      as well as removal of carbon. Ammonia in the waste was nitrified within 4 days.
      The denitrification of nitrate was achieved by the anoxic process, and 100%
      removal of nitrate was observed within 15 days of reactor operation.

PMID- 19396483
TI  - beta-Fructofuranosidase production by repeated batch fermentation with
      immobilized Aspergillus japonicus.
AB  - The fungus Aspergillus japonicus ATCC 20236 was immobilized in vegetal fiber and
      used in repeated batch fermentations of sucrose (200 g/l) for the production of
      beta-fructofuranosidases (FFase). The assays were performed during eight
      consecutive cycles that were completed in a total period of 216 h. After each 24
      h cycle of fermentation (except for the first cycle, which lasted 48 h), the
      fermented broth was replaced by fresh medium, and the FFase activity was
      determined in the replaced medium. The average value of FFase activity was a
      constant 40.6 U/ml at the end of the initial seven cycles, but had decreased by
      22% at the end of the eighth cycle. Concurrent with these high and constant FFase
      values, the hydrolyzing activity of this enzyme increased during the cycles,
      while the transfructosylating activity decreased. As a consequence, the maximum
      production of fructooligosaccharides of 134.60 g/l observed in the initial 30 h
      of fermentation (first cycle) had gradually decreased by the end of the
      subsequent cycles, reaching approximately 23% of this value during cycles 4-8.
      Based on these results, we conclude that the present immobilization system has a
      great potential for application in a semi-continuous process for the production
      of FFase, but further studies are necessary to maintain the FFase
      transfructosylation activity at high levels during the overall process.

PMID- 19396484
TI  - Evaluation of surface water quality using an ecotoxicological approach: a case
      study of the Alqueva Reservoir (Portugal).
AB  - BACKGROUND, AIM, AND SCOPE: Freshwater reservoirs can be impacted by several
      hazardous substances through inputs from agricultural activity, sewage
      discharges, and groundwater leaching and runoff. The water quality assessment is
      very important for implementation of the monitoring and remediation programs to
      minimize the risk promoted by hazardous substances in aquatic ecosystems.
      Evaluation of the degree of contamination of aquatic environments must not take
      in account only its chemical characterization but it must be complemented with
      biological assays, which determine potential toxic effects and allows an
      integrated evaluation of its effects in populations and aquatic ecosystem
      communities. The application of this type of strategy has clear advantages
      allowing a general evaluation of the effects from all the water components,
      including those due to unknown substances and synergic, antagonistic, or additive
      effects. There are only a few studies that reported ecotoxicological acute end
      points, for the assessment of surface water quality, and the relationship among
      toxicity results and the anthropogenic pollution sources and the seasonal period.
      The aim of this study was to assess the ecotoxicological characterization of the
      surface water from Alqueva reservoir (South of Portugal) and to evaluate the
      influence of anthropogenic sources of pollution and their seasonal variation in
      its toxicity. The construction of Alqueva reservoir was recently finished (2002)
      and, to our knowledge, an ecotoxicological assessment of its surface water has
      not been performed. Because of that, no information is available on the possible
      impact of pollutants on the biota. The surface water toxicity was assessed using
      acute and chronic bioassays. The results are to be used for developing a
      monitoring program, including biological methods. MATERIALS AND METHODS: Water
      samples were collected during 2006-2007, at each of the nine sampling sites
      selected in Alqueva reservoir. These sampling points allow an assessment at the
      upstream (Sra. Ajuda, Alcarrache, Alamos-Captacao), at the middle (Alqueva
      Montante, Alqueva-Mourao, Lucefecit), and at the downstream of the water line
      (Alqueva-Jusante; Ardila-confluencia; Moinho das Barcas). The campaigns occurred
      in February, March, May, July, September, and November of 2006 and February,
      March, and May of 2007. The rainy season comprised November, February, and March,
      and the dry season included May, July, and September. A total of 81 samples were
      collected during the study period. The physical-chemical parameters were analyzed
      following standard and recommended methods of analysis (APHA et al. 1998). The
      pesticide analyses were performed using gas chromatography according to DIN EN
      ISO 6468 (1996). Surface water ecotoxicity was evaluated using the following
      bioassays: Vibrio fischeri luminescence inhibition, Thamnocephalus platyurus
      mortality, and Daphnia magna immobilization and reproduction assay. The Spearman
      rank correlation coefficients were used to evaluate the associations between the
      water sample physicochemical properties (from each sampling station in each
      season) and the acute and chronic toxicological effects, with a level of
      significance p < 0.05. RESULTS: In the acute toxicity study, the species that was
      found to be the most sensitive was T. platyurus. T. platyurus detected a higher
      number of toxic water samples during the dry season. Concerning the luminescent
      inhibition of V. fischeri, the results showed that this organism detected a great
      number of toxic water samples in rainy seasons. The water samples, which promoted
      higher toxic effects towards this species, were from the north and from the
      middle of the reservoir. The correlation analysis showed that V. fischeri
      luminescent inhibition (%) was positively correlated with total phosphorus,
      chlorpyrifos, iron, and arsenic. T. platyurus mortality (%) was positively
      correlated with the water pH, 5-day biochemical oxygen demand (BOD(5)),
      chlorides, atrazine, simazine, terbuthylazine, and endosulfan sulfate contents.
      Although the surface waters did not promote acute toxicity to the crustacean D.
      magna, in the chronic exposure, a significant decrease in the number of juveniles
      per female was observed, mainly at the dry period. The number of juveniles per
      female, in the reproduction test of D. magna, was negatively correlated with pH,
      temperature, BOD(5), chloride, atrazine, simazine, terbuthylazine, and endosulfan
      sulfate. The water toxicity of the Alqueva water might be due principally to the
      intensive agriculture activities surrounding the reservoir and to the municipal
      wastewater discharges. DISCUSSION: The physicochemical parameters and the
      pesticide concentrations indicated that the water quality was worse in the north
      part of the reservoir system. These results are characteristic of the majority of
      reservoirs, once the construction of the dam promoted, by itself, the impounding
      of water flow and the increase of compound residence time. The toxicity tests
      corroborate with the chemical characterization. Acute toxicity of Alqueva water
      may be a result of the effect promoted by chlorpyrifos, endosulfan sulfate,
      phosphorus, and iron. Chronic toxicity may be a result of the effect of
      herbicides, arsenic, organic matter, endosulfan sulfate in mixture. Hence, the
      water toxicity of the Alqueva might be due principally to the intensive
      agriculture activities surrounding the reservoir and to the municipal wastewater
      discharges. CONCLUSIONS: This study has shown that a large number of samples from
      different sites of the Alqueva reservoir contained potentially toxic
      contaminants. The sites with impaired water quality were those located at the
      north of the reservoir and in the surrounding areas of intensive agricultural
      activity. The results demonstrated that the use of a screening of acute and
      chronic toxicity tests with organisms from different trophic levels and with
      distinct sensibilities allowed the detections of several patterns of toxicity
      from spatial and temporal variability promoted by natural or anthropogenic
      sources. The chronic responses showed, especially in the dry season, that some of
      the species belonging to this aquatic ecosystem might be at risk. RECOMMENDATIONS
      AND PERSPECTIVES: The V. fischeri and T. platyurus are two species that should be
      used in the acute bioassays for the ecotoxicological monitoring programs of this
      reservoir. It is recommended that other species, such as a productive organism
      (algae), be included in the next study, once the water reservoir had high levels
      of herbicides. Ecotoxicological assessment of surface water must integrate
      initial screening based on acute tests followed always by chronic bioassays. The
      results implicitly suggest that the implementation of processes of remediation by
      reducing pollutant input into the reservoir and by the implementation of water
      treatment processes is important and necessary.

PMID- 19396485
TI  - Seasonal variation of HCH isomers in open soil and plant-rhizospheric soil system
      of a contaminated environment.
AB  - BACKGROUND, AIM, AND SCOPE: Lindane, technically 1, 2, 3, 4, 5, 6
      hexachlorocyclohexane (gamma- HCH), is the most commonly detected organochlorine
      pesticide from diverse environmental compartments. Currently, India is the
      largest consumer and producer of lindane in the world. The production of lindane
      results in the generation of large quantities of waste HCH isomers (mainly alpha
      , beta- and delta-). All these isomers are toxic and have a long-range
      environmental transport potential. The aim of this study was to monitor the
      seasonal variation of HCH isomers in an open soil-plant-rhizospheric soil system
      of a contaminated industrial area. For this, selected plant species and their
      rhizospheric soil (soil samples collected at a depth range of 0-45 cm near to the
      root system) and open soil samples (soil samples collected (0-30 cm depth) from 1
      1.5 m away from the plant root system) were collected for 2 years (two summer
      seasons and two winter seasons). MATERIALS AND METHODS: Seven plant species along
      with their rhizospheric soil and open soil samples were collected seasonally from
      different parts of the industry. Plant samples were separated into root, leaf and
      stem. HCH isomers in plant and soil samples were extracted by matrix solid-phase
      dispersion extraction (MSPD) and Soxhlet extraction, respectively, followed by GC
      ECD. The seasonal difference in occurrence of HCH isomers in plant samples with
      their respective soil-system was studied by multivariate statistical approaches.
      RESULTS: The mean concentration of total HCH in plant samples, open soil and
      rhizospheric soil samples were found in the range of 14.12 to 59.29 mg kg(-1);
      38.64 to 104.18 mg kg(-1) and 8.38 to 26.05 mg kg(-1), respectively. Cluster
      grouping reveals that S. torvum and W. somnifera can accumulate more HCH than
      other studied species. DISCUSSION: There was a marked seasonal difference in the
      occurrence of HCH isomers in plant samples (p < 0.05) and open soil samples (p <
      0.01). Comparatively higher levels of HCH isomers were detected from plant
      samples during summer, while higher levels of HCH isomers were detected from soil
      samples during the winter season. There was no significant difference in seasonal
      variation of HCH isomers in rhizospheric soil samples; however, total HCH in
      rhizospheric soil samples were 4 to 5-fold lower than the open soil samples. The
      total concentration of HCH isomers in roots is linearly related to their
      rhizospheric HCH level. CONCLUSIONS: HCH isomers were detected in open soil,
      plants and rhizospheric soil samples. Monitoring studies clearly revealed that
      the above-mentioned industrial area is contaminated with all major isomers of
      HCH. Occurrence of all these isomers in the study area point out the lack of
      sustainable management practices of this industry for protecting the area from
      hazardous waste. The analytical results confirmed that accumulation depends upon
      the plant species, soil and climatic conditions. RECOMMENDATIONS AND
      PERSPECTIVES: Recently, alpha-, beta- and gamma-HCH have been nominated by the
      POPs Reviewing Committee for inclusion into the Stockholm Convention to address
      the HCH contamination on a global level. Therefore, there is an urgent need to
      stop the production of lindane and remediate contaminated soil sites. Based on
      the monitoring studies, the promising species like W. somnifera and S. torvum may
      be selected for the on-site phytoremediation of HCH-contaminated soil. The
      mismanagement of HCH residues from the organochlorine industry and their
      contemporary relevance often after decades of their deposition is one key example
      demonstrating the necessity to evaluate the waste deposits of the respective
      organochlorine productions and need for a strict waste management, and the
      necessity of an integrated pollution prevention and control strategy for the
      whole organochlorine industry including also the developing countries.

PMID- 19396486
TI  - Shoulder biomechanics: today's consensus and tomorrow's perspectives.
AB  - Shoulder biomechanics is a fast growing field, which is progressively expanding
      its focus to include more applied research. The papers included in this Special
      Issue confirm this trend. After a classification of the papers as dealing with
      fundamental or applied research through theoretical or experimental methods, in
      this Editorial we tried to summarize the elements of consensus and the open
      issues discussed during the last International Shoulder Group meeting, held in
      Bologna (Italy) in 2008.

PMID- 19396487
TI  - Conjunct rotation: Codman's paradox revisited.
AB  - This contribution mathematically formalizes Codman's idea of conjunct rotation, a
      term he used in 1934 to describe a paradoxical phenomenon arising from a closed
      loop arm movement. Real (axial) rotation is distinguished from conjunct rotation.
      For characterizing the latter, the idea of reference vector fields is developed
      to define the neutral axial position of the humerus for any given orientation of
      its long axis. This concept largely avoids typical coordinate singularities
      arising from decomposition of 3D joint motion and therefore can be used for
      postural (axial) assessment of the shoulder joint both clinically and in sports
      science in almost the complete accessible range of motion. The concept, even
      though algebraic rather complex, might help to get an easier and more intuitive
      understanding of axial rotation of the shoulder in complex movements present in
      daily life and in sports.

PMID- 19396488
TI  - Adduction contracture of the shoulder due to fibrous long head of the triceps in
      children.
AB  - OBJECTIVE: To evaluate the clinical and functional results of surgical treatment
      for fibrous long head of the triceps in children. MATERIALS AND METHODS: Data
      were analyzed from 32 patients (38 shoulders) aged over 5 years of age from
      August 1995 to December 2004. The adduction contracture, elbow flexed angles when
      the scapula was held in the chest wall, and scapulo-humeral angles in radiographs
      were measured. Surgical release of the long head of the triceps was performed.
      RESULTS: There were 22 females and 10 males in this study. Bilateral shoulder
      involvement was found in six patients. Only the right shoulder was involved in 5
      patients, and only the left in 21 patients. All 32 patients (38 shoulders)
      developed adduction contracture of the shoulder after repeated intramuscular
      injection of antibiotic(s) into the long head of the triceps. Thirty-four
      shoulders (29 patients) were classified as severe, and four shoulders (3
      patients) were classified as moderate. In all, we attained excellent results in
      36 shoulders (94.7%) and good results in two shoulders (5.3%). There have been no
      fair or poor results or complications so far. CONCLUSION: Generally, surgical
      treatment of adduction contracture of the shoulder has achieved good results,
      with improved shoulder function. Releasing the long head of the triceps is a
      simple and safe surgical technique.

PMID- 19396490
TI  - Impact of rhenium-188, gemcitabine, and 5-fluorouracil on cholangiocellular
      carcinoma cells: an in vitro study.
AB  - The purpose of this study was to compare the beneficial effects of radioactive
      stents and radioactive stents plus additional chemotherapy in the palliative
      treatment of cholangiocellular carcinomas. Cholangiocellular carcinoma cells (TFK
      1 cells) were treated either with 8 Gy (RTB group) or 16 Gy (RTA group) (188)Re
      or with (188)Re irradiation (8 Gy) combined with either gemcitabine (8 Gy/Gem) or
      5-fluorouracil (8 Gy/5-FU) at a dosage of 20 microg/ml medium for 4 days and
      subsequently compared with an untreated control group. Proliferation kinetics
      were assessed on days 4, 7, 11, 18, 25, and 32. Colony formation assays were
      performed on days 7, 18, and 32 and cell cycle distribution was examined on days
      4, 7, 11, 15, 25, and 39. Cell proliferation kinetics showed the lowest cell
      numbers in the 8 Gy/5-FU group (control, 15,390,000; RTA group, 8,394,000; RTB
      group, 5,609,000; 8 Gy/Gem group, 423,000; and 8 Gy/5-FU group, 297,667). In
      contrast, clonogenic activity on day 32 was lower in the 8 Gy/Gem group (control,
      29.3 colonies; RTB group, 23.1 colonies; 8 Gy/5-FU group, 21.5 colonies; 8
      Gy/Gem, 3.3 colonies; and even augmented in the RTA group, with 37.7 colonies).
      Cell cycle distribution showed similar curves for all groups on slightly
      different levels except for the 8 Gy/5-FU group, which showed a relatively
      augmented percentage of cells on day 7 in the G2 M cycle phase and on day 4 in
      the S phase. In conclusion, irradiation (8 Gy) with (188)Re administered, e.g.,
      via coated stents, combined with Gem could be a valid option for the treatment of
      CCCs.

PMID- 19396491
TI  - Identification and synthesis of a female-produced sex pheromone for the
      cerambycid beetle Prionus californicus.
AB  - Females of the large cerambycid beetle Prionus californicus produce a powerful
      sex pheromone that attracts males. The pheromone was adsorbed on solid phase
      microextraction (SPME) fibers inserted into the ovipositor sheath and analyzed by
      coupled gas chromatography-electroantennogram detection and GC-mass spectrometry.
      The pheromone was identified as an isomer of 3,5-dimethyldodecanoic acid by a
      combination of retention index comparisons and mass spectral interpretation. The
      mass spectrum was misleading because it exhibited enlarged fragment ions that
      were not representative of branch points or other obvious stabilizing structural
      elements. The structure was verified by synthesis of 3,5-dimethyldodecanoic acid
      as a mixture of all four possible isomers, and this mixture was highly attractive
      to male beetles in field bioassays. The SPME extracts also contained several
      other compounds that were tentatively identified as chain-extended homologs of
      the main pheromone component. This pheromone should prove useful for sampling and
      management of the beetle, which is an important pest of hops, and an occasional
      pest in a variety of orchard crops. Although this is the first female-produced
      pheromone to be identified from the Cerambycidae, there is considerable evidence
      for pheromone production by females of other species in the subfamily Prioninae.
      Thus, this pheromone and the associated methodology used in its identification
      should be useful in the identification of female-produced attractant pheromones
      from other members of the subfamily.

PMID- 19396493
TI  - Editorial: Combined modality treatment of resectable and borderline resectable
      pancreas cancer: expert consensus conference.

PMID- 19396494
TI  - Surgical treatment of resectable and borderline resectable pancreatic cancer:
      expert consensus statement by Evans et al.

PMID- 19396495
TI  - AHPBA/SSO/SSAT Consensus Conference on Resectable and Borderline Resectable
      Pancreatic Cancer: rationale and overview of the conference.

PMID- 19396496
TI  - Pretreatment assessment of resectable and borderline resectable pancreatic
      cancer: expert consensus statement.

PMID- 19396497
TI  - A motif-based approach to network epidemics.
AB  - Networks have become an indispensable tool in modelling infectious diseases, with
      the structure of epidemiologically relevant contacts known to affect both the
      dynamics of the infection process and the efficacy of intervention strategies.
      One of the key reasons for this is the presence of clustering in contact
      networks, which is typically analysed in terms of prevalence of triangles in the
      network. We present a more general approach, based on the prevalence of different
      four-motifs, in the context of ODE approximations to network dynamics. This is
      shown to outperform existing models for a range of small world networks.

PMID- 19396499
TI  - PHQ-9 and PHQ-2 in Western Kenya.

PMID- 19396500
TI  - Residents' experience of scholarly activities is associated with higher
      satisfaction with residency training.
AB  - BACKGROUND: The Ministry of Health, Labour and Welfare of Japan has been
      promoting participation in scholarly activities for physicians during residency
      training. However, there is debate regarding whether this is worthwhile for
      residents. OBJECTIVE: To evaluate residents' opinions of engaging in scholarly
      activities and identify factors associated with overall satisfaction with their
      training program. DESIGN: Cross-sectional national survey. PARTICIPANTS: 1,124
      second-year residents in teaching hospitals in Japan in 2007 MEASUREMENTS:
      Collected data included demographics, teaching hospital characteristics and
      resources, residents' research experiences, including type of activities,
      barriers to performing scholarly activities, residents' opinions of scholarly
      requirements, and resident satisfaction with their residency program. RESULTS:
      1,124 residents/1,500 responded for a response rate of 74.9%. Our data showed
      that 60.2% of Japanese residents engaged in some type of scholarly activity.
      Barriers included: "No resident time"; "No mentor;" and "No resident interest."
      Sixty-three percent of residents thought that research should be a residency
      requirement. In multivariate logistic analysis, residents' overall satisfaction
      with their residency program was significantly associated with participation in
      research activity (odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.1);
      male gender (OR, 1.5; 95% CI: 1.1-2.2); satisfaction with residency compensation
      (OR, 3.8; 95% CI, 2.6-5.0), and satisfaction with the residency curriculum (OR,
      19.5; 95% CI, 13.7-27.7). CONCLUSIONS: The majority of residents surveyed thought
      that research activity was worthwhile. Residents' participation in research
      activity was associated with higher levels of satisfaction with residency
      training. Implementing measures to overcome existing barriers may have
      educational benefits for residents.

PMID- 19396503
TI  - Correlates of non-concordance between perceived and objective measures of
      walkability.
AB  - BACKGROUND: Objective and self-reported physical environmental attributes have
      been related to physical activity. PURPOSE: We examined the characteristics of
      adults who are resident in objectively identified high walkable neighborhoods but
      whose perceptions of neighborhood attributes are not concordant with objective
      attributes relating to high walkability. METHODS: Neighborhood built-environment
      attributes relating to walkability (dwelling density, intersection density, land
      use mix, and net retail area) were determined objectively, using Geographic
      Information System databases; data on corresponding perceptions of local
      environment attributes (from the Neighborhood Environment Walkability Scale) were
      derived from a self-completion survey of a socially diverse sample of 2,650
      adults aged 19 to 65. Objective and perceived walkability attributes were
      categorized using median splits, and correlates of non-concordance were
      determined using multiple logistic regression models. RESULTS: There was a fair
      overall agreement between objectively determined walkability and perceived
      walkability (Kappa = 0.35, 95% CI = 0.31-0.39). Among those resident in
      objectively assessed high walkable areas (n = 1,063), 32.1% perceived them to be
      low walkable; conversely, 32.7% (n = 1,021) resident in objectively determined
      low walkability areas perceived them to be high. For residents of objectively
      determined high walkable areas, the characteristics that differentiated those
      with perceptions of low walkability (non-concordant perceptions) from those with
      concordant perceptions of high walkability were: not being university-educated
      (OR = 1.47, 95% CI = 1.06-2.04); having lower household incomes (OR = 1.54, 95%
      CI = 1.09-2.17); being overweight (OR = 1.46, 95% CI = 1.03-2.07); and walking
      fewer days per week for transport (OR = 1.75, 95% CI = 1.11-2.70). Higher walking
      times and more positive cognitive variables were noted among participants who
      lived in a neighborhood with low walkability that was perceived as high compared
      to those who lived in a high walkable environment that was perceived as low
      walkable. CONCLUSION: Adults with lower educational attainment and lower incomes,
      who were overweight, or who were less physically active for transportation
      purposes, were more likely to misperceive their high walkable neighborhood as low
      walkable. There is the potential for physical activity promotion and persuasion
      strategies to address non-concordant perceptions, especially among those who live
      in high walkable environments but perceive them to be low and also among those
      who are socially disadvantaged and are less active. Perceptions of environmental
      attributes may be more strongly correlated with cognitive antecedents and with
      behavior than are objective measures.

PMID- 19396502
TI  - The synergistic effect of autograft and BMP-7 in the treatment of atrophic
      nonunions.
AB  - Combining autologous bone graft and recombinant human bone morphogenetic protein
      7 (BMP-7) to treat long-bone fracture aseptic atrophic nonunions theoretically
      could promote bone healing at higher rates than each of these grafting agents
      separately. We retrospectively reviewed prospectively collected data on patient
      general characteristics, clinical outcomes, and complications over 3 years to
      determine the healing rates and the incidence of complications and adverse events
      of this "graft expansion rationale." There were 45 patients (32 male) with a
      median age of 43 years (range, 19-76 years). Minimum followup was 12 months
      (mean, 24.5 months; range, 12-65 months). There were seven humeral, 19 femoral,
      and 19 tibial nonunions. The median number of prior operations was two (range, 1
      7). All fractures united. Clinical and radiographic union occurred within a
      median of 5 months (range, 3-14 months) and 6 months (range, 4-16 months),
      respectively. Thirty-nine (87%) patients returned to their preinjury occupation
      at a mean of 4.2 months (range, 3-6 months). The median visual analog scale pain
      score was 0.9 (range, 0-2.8; maximum 10), and the median functional score was 86
      (range, 67-95; maximum 100) at the final followup. BMP-7 as a bone-stimulating
      agent combined with conventional autograft resulted in a nonunion healing rate of
      100% in these 45 patients. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      the Guidelines for Authors for a complete description of levels of evidence.

PMID- 19396504
TI  - Influence of 99mTc-tetrofosmin SPECT myocardial perfusion imaging on the
      prediction of future adverse cardiac events.
AB  - BACKGROUND: The impact of myocardial perfusion imaging (MPI) on prediction of
      risk for future cardiac events was examined by comparing predictions based on
      clinical information alone and in combination with MPI findings. METHODS AND
      RESULTS: A 3-cardiologist Cardiac Event Prediction Panel (CEPP) estimated three
      year cardiac event (non-fatal MI; aborted sudden cardiac death; cardiac death)
      risk based on clinical data (C) for 371 subjects. CEPP repeated this estimation
      after receiving Summed Stress Scores (SSS) and Summed Rest Scores (SRS) from
      blinded reading of rest-stress (99m)Tc-tetrofosmin MPI SPECT studies (C + MPI).
      The C and C + MPI estimates were then compared with three-year and total event
      rates. MPI was normal (SSS </= 3) in 227 patients (61%), mildly abnormal (SSS 4
      8) in 31 (8%), moderately abnormal (SSS 9-13) in 36 (10%), and severely abnormal
      (SSS > 13) in 77 (21%). Eighteen cardiac events occurred within 3 years and 33
      occurred during a mean follow-up of 3.9 years. C + MPI estimates of low risk (<1
      1.5%/year) identified significantly more patients who did not have events than C.
      C + MPI three-year event-rate predictions were more accurate than those made with
      C (P < .01). C + MPI categorization also provided better delineation of
      incremental risk on time-to-event analyses. CONCLUSIONS: (99m)Tc-tetrofosmin MPI
      single photon emission computed tomography (SPECT) findings significantly improve
      accuracy of cardiac event rate prediction compared to those based on clinical
      information alone.

PMID- 19396505
TI  - Ultrasound evidence of the optimal wrist position for radial artery cannulation.
AB  - PURPOSE: Radial artery cannulation is a common medical procedure for anesthesia
      and critical care. To establish the ideal wrist position for radial artery
      cannulation, we performed ultrasound examinations of the radial artery to
      investigate the effect of the angle of wrist extension on radial artery
      dimensions. CLINICAL FEATURES: Measurements were performed in 17 healthy subjects
      and 17 surgical patients scheduled for coronary artery bypass graft (CABG)
      surgery. The radial artery was echographically visualized near the styloid
      process of the radius at the wrist. Radial artery dimensions were measured at
      wrist joint angles of 0, 15, 30, 45, 60 and 75 degrees . OBSERVATIONS: In both
      groups, radial artery height was affected by the wrist joint angle. Vessel height
      was decreased at 60 degrees (one way ANOVA P = 0.027 vs 0 degrees ) and 75
      degrees (P < 0.001 vs 0, 15, 45 degrees ) in healthy subject and at 75 degrees in
      CABG patients (P < 0.001 vs 0 degrees ). The mean differences in radial artery
      height at 0 and 75 degrees were 0.33 +/- 0.09 mm and 0.20 +/- 0.06 mm for healthy
      and CABG patients, respectively. Vessel width was not affected by wrist joint
      angulation up to 75 degrees of extension. CONCLUSION: Our results demonstrate
      that in healthy subjects, radial artery dimensions are unaltered when the wrist
      joint is extended up to an angle of 45 degrees . Extension at 60 degrees for
      healthy subjects and 75 degrees for CABG patients, however, results in a decrease
      in the height of the radial artery, which could possibly render arterial
      catheterization more difficult.

PMID- 19396506
TI  - Obstetric hemorrhage during an EXIT procedure for severe fetal airway
      obstruction.
AB  - PURPOSE: To report a case of massive obstetric hemorrhage occurring during
      Cesarean delivery for an ex utero intrapartum treatment (EXIT) procedure. Methods
      to optimize the anesthetic, obstetric, and perinatal management are discussed.
      CLINICAL FEATURES: A healthy parturient underwent an urgent EXIT procedure at 32
      weeks gestation for a giant fetal neck mass. During the intraoperative period,
      severe intraoperative hemorrhage occurred from the site of the uterine incision.
      No evidence of placental bleeding, premature placental separation, or inadequate
      uterine relaxation was observed during the perioperative period. Placement of a
      uterine stapling device was unsuccessful in achieving adequate surgical
      hemostasis. Initial attempts with laryngoscopy and rigid bronchoscopy to secure
      the fetal airway on placental support were unsuccessful, and early termination of
      placental support was deemed necessary due to the severity of maternal blood
      loss. After full delivery of the neonate and termination of placental support,
      neonatal ventilation with bag-mask ventilation was achieved and successful
      endotracheal intubation occurred during repeat bronchoscopy. CONCLUSIONS: The
      risk of obstetric hemorrhage due to uterine relaxation and inadequate surgical
      hemostasis in patients undergoing EXIT procedures is poorly reported. To reduce
      adverse maternal and neonatal outcomes, the premature termination of placental
      support during EXIT procedures may be required in the setting of severe obstetric
      hemorrhage.

PMID- 19396507
TI  - Effect of manual in-line stabilization of the cervical spine in adults on the
      rate of difficult orotracheal intubation by direct laryngoscopy: a randomized
      controlled trial.
AB  - PURPOSE: Although manual in-line stabilization (MILS) is commonly used during
      endotracheal intubation in patients with either known or suspected cervical spine
      instability, the effect of MILS on orotracheal intubation is poorly documented.
      This study evaluated the rate of failed tracheal intubation in a fixed time
      interval with MILS. METHODS: Two hundred elective surgical patients were
      randomized into two groups. In the MILS group, the patient's head was stabilized
      in a neutral position by grasping the patient's mastoid processes to minimize any
      head movement during tracheal intubation. In the control group, the patient's
      head rested in an optimal position for tracheal intubation. A 30-sec period was
      allowed to complete tracheal intubation with a #3 Macintosh laryngoscope blade.
      The primary endpoint was the rate of failed tracheal intubation at 30 sec.
      Secondary endpoints included tracheal intubation time and the Cormack & Lehane
      grade of laryngoscopy. RESULTS: Patient characteristics were similar with respect
      to demographic data and risk factors for difficult tracheal intubation. The rate
      of failed tracheal intubation at 30 sec was 50% (47/94) in the MILS group
      compared to 5.7% (6/105) in the control group (P < 0.0001). Laryngoscopic grades
      3 and 4 were more frequently observed in the MILS group. Mean times for
      successful tracheal intubation were 15.8 +/- 8.5 sec and 8.7 +/- 4.6 sec for the
      MILS and control groups, respectively (mean difference 7.1, CI(95%) 5.0-9.3, P <
      0.0001). All patients who failed tracheal intubation in the MILS group were
      successfully intubated when MILS was removed. CONCLUSION: In patients with
      otherwise normal airways, MILS increases the tracheal intubation failure rate at
      30 sec and worsens laryngeal visualization during direct laryngoscopy.

PMID- 19396508
TI  - Carotid arterial cannulation: removing the risk with ultrasound?

PMID- 19396509
TI  - Pharmacogenomics and perioperative medicine: implications for modern clinical
      practice.

PMID- 19396510
TI  - Identification of several intracellular carbohydrate-degrading activities from
      the halophilic archaeon Haloferax mediterranei.
AB  - Three different amylolytic activities, designated AMY1, AMY2, and AMY3 were
      detected in the cytoplasm of the extreme halophilic archaeon Haloferax
      mediterranei grown in a starch containing medium. This organism had also been
      reported to excrete an alpha-amylase into the external medium in such conditions.
      The presence of these different enzymes which are also able to degrade starch may
      be related to the use of the available carbohydrates and maltodextrins, including
      the products obtained by the action of the extracellular amylase on starch that
      may be transported to the cytoplasm of the organism. The behavior of these
      intracellular hydrolytic enzymes on starch is reported here and compared with
      their extracellular counterpart. Two of these glycosidic activities (AMY1, AMY3)
      have also been purified and further characterized. As with other halophilic
      enzymes, they were salt dependent and displayed maximal activity at 3 M NaCl, and
      50 degrees C. The purification steps and molecular masses have also been
      reported. The other activity (AMY2) was also detected in extracts from cells
      grown in media with glycerol instead of starch and in a yeast extract medium.
      This enzyme was able to degrade starch yielding small oligosaccharides and
      displayed similar halophilic behavior with salt requirement in the range 1.5-3 M
      NaCl.

PMID- 19396511
TI  - Quantitative analysis of carbon balance in the reproductive organs and leaves of
      Cinnamomum camphora (L.) Presl.
AB  - We investigated seasonal changes in dry mass and CO(2) exchange rate in fruit and
      leaves of the evergreen tree Cinnamomum camphora with the aim of quantitatively
      determining the translocation balance between the two organs. The fruit dry mass
      growth peaked in both August and October: the first increase was due to fruit
      pulp development and the second to seed development. Fruit respiration also
      increased with the rapid increase in fruit dry mass. Therefore, the carbohydrates
      required for fruit development showed two peaks during the reproductive period.
      Fruit photosynthesis was relatively high in early August, when fruit potentially
      re-fixed 75% of respired CO(2), indicating that fruit photosynthesis contributed
      15-35% of the carbon requirement for fruit respiration. Current-year leaves
      completed their growth in June when fruit growth began. Current-year leaves
      translocated carbohydrates at a rate of approximately 10-25 mg dry weight (dw)
      leaf(-1) day(-1) into other organs throughout the entire fruit growth period.
      This rate of translocation from current-year leaves was much higher than the
      amount of carbohydrate required for reproduction (ca. 3 mg dw fruit(-1) day(-1)).
      Given the carbon balance between fruit and current-year leaves, carbohydrates for
      reproduction were produced within the current-year fruit-bearing shoots. C.
      camphora would be adaptive for steadily supplying enough amount of carbohydrate
      to the fruits, as there was little competition for carbohydrates between the two
      organs. As assimilates by leaves are used for processes such as reproduction and
      the formation of new shoots, photosynthesis by reproductive organs is considered
      to be important to compensate for reproductive cost.

PMID- 19396512
TI  - Findings of hepatopulmonary syndrome on breath-hold perfusion SPECT-CT fusion
      images.
AB  - Pulmonary perfusion SPECT-CT fusion images were used to characterize CT
      manifestations of intrapulmonary arteriovenous communications (AVC) causing right
      to-left shunt and hepatopulmonary syndrome (HPS). After scanning the whole body
      and obtaining multiple view images of the lung, deep-inspiratory breath-hold
      (DIBrH) SPECT was obtained in 2 patients with HPS, which was automatically and
      three-dimensionally co-registered with DIBrH CT. In both patients, the whole body
      scan depicted systemic organs and confirmed the existence of right-to-left shunt.
      DIBrH SPECT-CT fusion images showed that perfusion defects were predominantly
      located at subpleural reticulo-nodular opacities and/or dilated vessels in the
      lung base. Subpleural reticulo-nodular opacities and/or dilated vessels in the
      lung base appear to be characteristic CT manifestation of intrapulmonary AVC in
      HPS.

PMID- 19396513
TI  - Relationship between an effective dose of imatinib, body surface area, and trough
      drug levels in patients with chronic myeloid leukemia.
AB  - The standard dose of imatinib for the treatment of chronic-phase chronic myeloid
      leukemia (CML) is 400 mg/day. Some patients receive reduced doses of imatinib
      because of serious adverse effects. Recently, the effective plasma threshold for
      trough imatinib levels was demonstrated to be 1,002 ng/mL. In this study, we
      evaluated the association of an imatinib dose with trough plasma concentrations
      and clinical outcomes in 31 patients with chronic-phase CML who were treated at
      Kumamoto University Hospital. Twenty-seven patients were optimally treated with
      various doses of imatinib. The mean (+/-SD) trough plasma concentrations of
      imatinib were 1.40 +/- 0.57 microg/mL in 13 patients receiving 400 mg/day and
      1.15 +/- 0.44 microg/mL in 9 patients receiving 300 mg/day as an effective dose.
      Mean trough levels of the two groups were not significantly different and
      exceeded the effective plasma threshold. Body surface area (BSA) was
      significantly smaller in patients receiving the reduced dose compared with those
      receiving the standard dose (p = 0.001). The effective imatinib dose was
      associated with age and gender as well as BSA. A reduced dose of 300 mg/day of
      imatinib may be sufficient for the treatment of CML patients with smaller body
      size, particularly when intolerability arises.

PMID- 19396514
TI  - Loop-mediated isothermal amplification (LAMP): a rapid, accurate, and cost
      effective diagnostic method for infectious diseases.
AB  - Loop-mediated isothermal amplification (LAMP) is an established nucleic acid
      amplification method offering rapid, accurate, and cost-effective diagnosis of
      infectious diseases. This technology has been developed into commercially
      available detection kits for a variety of pathogens including bacteria and
      viruses. The current focus on LAMP methodology is as a diagnostic system to be
      employed in resource-limited laboratories in developing countries, where many
      fatal tropical diseases are endemic. The combination of LAMP and novel
      microfluidic technologies such as Lab-on-a-chip may facilitate the realization of
      genetic point-of-care testing systems to be used by both developed and developing
      countries in the near future. This review will describe the historical, current,
      and future developments of such technologies.

PMID- 19396515
TI  - Mechanism and implication of cephalosporin penetration into oropharyngeal mucosa.
AB  - The aim of this study was to explore the mechanism(s) by which oral
      cephalosporins penetrate into human oropharyngeal mucosa, and thus, the
      availability of sufficient concentrations at the site of infection. Two oral
      cephalosporin prototypes, cephalexin (first generation) and cefixime (third
      generation), were administered to five healthy subjects at two different visits
      with a 1-week washout period. Plasma and saliva samples were collected and drug
      concentrations were measured using an appropriate HPLC method. The maximum plasma
      concentrations (Cmax) of cefixime and cephalexin were 2.97+/-0.24 microg ml(-1)
      and 77.65+/-18.91 microg ml(-1), respectively. These concentrations were
      associated with a maximum salivary concentration (CSmax) of 0.56 microg ml(-1)
      for cefixime and 3.34 microg ml(-1) for cephalexin. Such levels exceed the
      reported minimal inhibitory concentration (MIC) for Streptococcus pyogenes and
      Streptococcus pneumoniae. The average concentration of cefixime in saliva
      corresponded to its plasma free fraction (saliva/plasma [S/P] ratio; 0.34).
      However, this observation was not true for cephalexin, for which antibiotic
      concentrations in the saliva did not appear to correspond to its plasma free
      fraction (0.8-0.85), with an S/P ratio of only 0.092. Our findings indicate that
      an active transport mechanism exists for cefixime excretion into human
      oropharyngeal mucosa, whereas cephalexin is passively diffused, although to a
      limited extent, as measured by its salivary concentrations.

PMID- 19396516
TI  - A rapid screening method for Panton-Valentine leucocidin-positive community
      acquired methicillin-resistant Staphylococcus aureus belonging to multilocus
      sequence type 30 and its related clone using a combination of multiplex PCR and
      pulsed-field gel electrophoresis.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), which
      is often positive for Panton-Valentine leucocidin (PVL), is increasingly noted as
      an emerging pathogen worldwide. In Japan, PVL-positive CA-MRSA belonging to
      multilocus sequence type (ST) 30 has spread and caused, for example, pediatric
      death due to community-acquired pneumonia and severe pelvic abscesses in an
      athlete. In this study, we investigated a new rapid screening method for PVL
      positive ST30 CA-MRSA and its related clone by a combination of multiplex
      polymerase chain reaction (M-PCR) and pulsed-field gel electrophoresis (PFGE).
      For M-PCR, the targets of the assay were the five genes for PVL, collagen
      adhesin, bone sialoprotein adhesin, methicillin resistance, and S. aureus
      specific thermostable nuclease. Only PVL-positive ST30 CA-MRSA strains produced
      all five bands in M-PCR. With PFGE, Japanese strains and most foreign strains of
      PVL-positive ST30 CA-MRSA shared the same pattern. Moreover, PFGE distinguished
      current PVL-positive CA-MRSA ST30/spa19 strains from previous PVL-positive MRSA
      ST30/spa43 strains (which were isolated at the time of nosocomial MRSA outbreaks
      in the late 1980s and early 1990s) in Japan. Thus, the M-PCR assay rapidly, and
      the M-PCR/PFGE combination assay more precisely, discriminated between PVL
      positive ST30 CA-MRSA (or its related clone) and PVL-positive CA-MRSA belonging
      to other ST types such as ST1, 8, 59, and 80, PVL-negative CA-MRSA, hospital
      acquired MRSA, methicillin-susceptible S. aureus, or coagulase-negative
      staphylococci (CNS), including MRCNS. This screening method is more useful than
      genotyping for routine work in many clinical laboratories.

PMID- 19396517
TI  - Genotypes, intrafamilial transmission, and virulence potential of nasal
      methicillin-resistant Staphylococcus aureus from children in the community.
AB  - Pediatric outpatients and healthy children in the community were examined for
      nasal methicillin-resistant Staphylococcus aureus (MRSA) in Japan. MRSA isolation
      frequencies were 0.7% (3/426) and 3.7% (5/136), respectively, in pediatric
      outpatients and healthy children in the community (overall frequency, 1.4%). The
      frequency of MRSA isolation was higher in children 5-9 years of age compared with
      the other age groups. All eight MRSA strains isolated were Panton-Valentine
      leukocidin-negative. Of these, three with the genotype multilocus sequence type
      (ST) 8/spa606/SCCmecIV (2 cases) and ST88/spa999/SCCmecIV/exfoliative toxin A
      gene (eta) were identical or similar to MRSA from bullous impetigo, determined by
      pulsed-field gel electrophoresis. One strain with ST764 (ST5
      variant)/spa2/SCCmecII/staphylococcal enterotoxin B gene seb2 (seb variant) was
      similar to MRSA from bacteremia, and one with ST5/spa2/SCCmecII was the Pandemic
      New York/Japan clone. The remaining three strains, with ST22/spa998/SCCmecI,
      ST380/spa799/SCCmecIV, and ST857/spa416/SCCmecII, have not been identified. All
      MRSA strains were resistant to one or more non-beta-lactam antibiotics, and the
      ST5 and ST764 strains were multidrug-resistant. Family analysis demonstrated
      parent-to-child transmission (for ST8 and ST764), as well as acquisition from
      outside the family (for ST8 and ST380). The data suggest that young school-age
      children have a higher carriage rate of nasal MRSA than children of other ages,
      and that not only community-acquired MRSA strains but also MRSA strains with
      characteristics of hospital-acquired MRSA are spreading in the community.

PMID- 19396518
TI  - Rapid detection of eight causative pathogens for the diagnosis of bacterial
      meningitis by real-time PCR.
AB  - We aimed to detect causative pathogens in cerebrospinal fluid (CSF) collected
      from patients diagnosed with bacterial meningitis by real-time polymerase chain
      reaction (PCR). In addition to Streptococcus pneumoniae, Haemophilus influenzae,
      and Mycoplasma pneumoniae described previously, five other pathogens, Neisseria
      meningitidis, Escherichia coli, Streptococcus agalactiae, Staphylococcus aureus,
      and Listeria monocytogenes, were targeted, based on a large-scale surveillance in
      Japan. Results in CSF from neonates and children (n=150), and from adults (n=18)
      analyzed by real-time PCR with molecular beacon probes were compared with those
      of conventional culturing. The total time from DNA extraction from CSF to PCR
      analysis was 1.5 h. The limit of detection for these pathogens ranged from 5
      copies to 28 copies per tube. Nonspecific positive reactions were not recognized
      for 37 microorganisms in clinical isolates as a negative control. The pathogens
      were detected in 72.0% of the samples by real-time PCR, but in only 48.2% by
      culture, although the microorganisms were completely concordant. With the real
      time PCR, the detection rate of H. influenzae from CSF was high, at 45.2%,
      followed by S. pneumoniae (21.4%), S. agalactiae (2.4%), E. coli (1.8%), L.
      monocytogenes (0.6%), and M. pneumoniae (0.6%). The detection rate with PCR was
      significantly better than that with cultures in patients with antibiotic
      administration (chi2=18.3182; P=0.0000). In conclusion, detection with real-time
      PCR is useful for rapidly identifying the causative pathogens of meningitis and
      for examining the clinical course of chemotherapy.

PMID- 19396519
TI  - The effect of inhaled corticosteroids on Chlamydophila pneumoniae and Mycoplasma
      pneumoniae infection in children with bronchial asthma.
AB  - The purpose of this study was to clarify whether inhaled corticosteroids (ICSs)
      increased the infectious load of Chlamydophila pneumoniae and/or Mycoplasma
      pneumoniae in the respiratory tracts of asthmatic children. We studied a total of
      310 outpatients with chronic stable asthma. Real-time polymerase chain reaction
      (PCR)-positive results for C. pneumoniae were obtained in 21 of 310 (6.8%) throat
      samples and 21 of 293 (7.2%) nasopharyngeal samples. There was no significant
      difference in the rate of detection or in the quantity of detection for C.
      pneumoniae between the ICS group and the non-ICS group, nor were there
      differences among groups classified by Japanese pediatric guidelines (JPGL)
      severity criteria. Real-time PCR-positive results for M. pneumoniae were obtained
      in 60 of 310 (19.4%) throat samples and 49 of 293 (16.7%) nasopharyngeal samples.
      There was no significant difference in the rate of detection or the quantity of
      detection between the ICS group and the non-ICS group, nor were there differences
      among age groups. The results of this research do not support the hypothesis that
      ICSs influence the infectious load of C. pneumoniae and M. pneumoniae. ICSs did
      not increase C. pneumoniae or M. pneumoniae infection in the upper respiratory
      tract, in contrast to the effect of ICSs in causing oral candidiasis. Our data
      exclude the concern that there is an increase in C. pneumoniae and M. pneumoniae
      infections due to ICS use, the use of ICSs being the gold standard in the long
      term anti-inflammatory treatment of persistent asthma in children and adults.

PMID- 19396520
TI  - Clinical efficacy of oral administration of 200 mg gatifloxacin once daily for 3
      days for the treatment of patients with uncomplicated cystitis.
AB  - To assess the clinical efficacy of oral antibiotic administration for the
      treatment of lower urinary tract infection (UTI), 102 female patients were given
      gatifloxacin (200 mg once daily for 3 days). Five to nine days after treatment,
      drug safety and clinical efficacy were assessed by evaluation of urinalysis and
      symptoms. Further, the patients were asked to report by mail whether they had
      persistent or recurrent symptoms at 4-6 weeks after treatment. The overall
      clinical cure rate was 93.1% (95/102). Of 94 patients with susceptible pathogens
      and 8 with resistant pathogens, 89 (94.7%) and 6 (75.0%), respectively, were
      judged as clinically cured. Four to 6 weeks after treatment, 57 (55.9%) of the
      102 patients reported their micturition status by mail, and 6 (10.5%) of them
      claimed that they had some symptoms. The outcomes of this study suggest that a
      therapeutic regimen such as administration of fluoroquinolones once daily for 3
      days can be recommended for the treatment of uncomplicated cystitis.

PMID- 19396521
TI  - The efficacy of high-dose penicillin for community-acquired pneumonia diagnosed
      by pneumococcal urine antigen test.
AB  - We analyzed the efficacy of both the Streptococcus pneumoniae urine antigen test
      as a quick diagnostic tool and the administration of high-dose penicillin in
      response to a positive S. pneumoniae urine antigen test. We conducted a
      retrospective analysis of 48 cases of pneumococcal pneumonia, in which the
      patients were treated with high-dose penicillin. All the cases were diagnosed by
      a positive urine antigen test. Treatment with high-dose penicillin was effective
      in 43 of the 48 patients. This treatment was also effective in 12 of 16 culture
      confirmed cases with low susceptibility to penicillin. Eleven patients who were
      positive for the S. pneumoniae urine antigen test but culture-negative showed
      clinical improvement with high-dose penicillin. Pneumonia caused by S. pneumoniae
      appeared to be treated safely and effectively with high-dose penicillin based on
      positive results of the urine antigen test, as penicillin resistance was unlikely
      to be a problem.

PMID- 19396522
TI  - Fluoroquinolones reduce carrageenan-induced edema in rats and the involvement of
      the glucocorticoid receptor system.
AB  - We studied the effect of fluoroquinolones (FQs) on carrageenan-induced edema in
      the rat footpad. Ciprofloxacin, gatifloxacin, sparfloxacin, norfloxacin, and
      enoxacin (s.c., 100 mg/kg), which have piperazinyl and/or cyclopropyl groups,
      inhibited carrageenan-induced edema, whereas levofloxacin, tosufloxacin, and
      pazufloxacin did not. The reduction of edema by ciprofloxacin, sparfloxacin, and
      enoxacin was abolished by pretreatment with mifepristone, an antagonist of the
      glucocorticoid receptor. These results suggest that FQs with piperazinyl and/or
      cyclopropyl groups can modify biological responses through enhancing the
      glucocorticoid-glucocorticoid receptor system.

PMID- 19396523
TI  - Anti-interferon-gamma autoantibody in a patient with disseminated Mycobacterium
      avium complex.
AB  - We report the case of a 44-year-old woman with disseminated Mycobacterium avium
      complex (MAC) infection involving multiple bone lesions despite a normal healthy
      status until 6 months previously. Because she was suspected to have acquired
      immunodeficiency, we tested interferon (IFN)-gamma production by peripheral blood
      mononuclear cells (PBMC) after phytohemagglutinin (PHA) or anti-CD3 stimulation,
      and found that these cells produced no, or undetectable, levels of IFN-gamma in
      the presence of the patient's plasma, but produced nearly normal levels of IFN
      gamma in the presence of healthy donor plasma. Since the IgG fraction of the
      patient's plasma was capable of blocking in vitro responses to IFN-gamma, the
      cause of disseminated MAC infection in this case appeared to be anti-IFN-gamma
      autoantibodies. To reduce the titer of anti-IFN-gamma autoantibodies, the patient
      received intravenous immunoglobulin (IVIG). However, titer of autoantibodies
      changed little compared to that before IVIG administration. According to our
      literature search, this is only the second case of disseminated MAC infection
      associated with anti-IFN-gamma autoantibodies in Japan.

PMID- 19396525
TI  - Metabolism of polyamines and oxidative stress in the brain of cholestatic rats.
AB  - In a recently published article in "Amino Acids" it was shown that obstructive
      jaundice of 9 days' duration in rats induces significant alterations of
      polyamines' metabolism in the brain, which might play an important pathogenetic
      role in cholestatic brain injury. The authors proposed that alterations of
      polyamines in cholestatic brain might induce neuronal toxicity through a
      mechanism that implicates the production of reactive oxygen species and oxidative
      stress, although this parameter was not evaluated in their study. This hypothesis
      is supported by our recent findings on brain oxidative status in rats with
      obstructive jaundice of 10 days' duration. Potential interrelations of the two
      studies' findings are discussed in this commentary.

PMID- 19396526
TI  - Effect of maternal panic disorder on mother-child interaction and relation to
      child anxiety and child self-efficacy.
AB  - To determine whether mothers with panic disorder with or without agoraphobia
      interacted differently with their children than normal control mothers, 86
      mothers and their adolescents (aged between 13 and 23 years) were observed during
      a structured play situation. Maternal as well as adolescent anxiety status was
      assessed according to a structured diagnostic interview. Results showed that
      mothers with panic disorder/agoraphobia showed more verbal control, were more
      criticizing and less sensitive during mother-child interaction than mothers
      without current mental disorders. Moreover, more conflicts were observed between
      mother and child dyadic interactions when the mother suffered from panic
      disorder. The comparison of parenting behaviors among anxious and non-anxious
      children did not reveal any significant differences. These findings support an
      association between parental over-control and rejection and maternal but not
      child anxiety and suggest that particularly mother anxiety status is an important
      determinant of parenting behavior. Finally, an association was found between
      children's perceived self-efficacy, parental control and child anxiety symptoms.

PMID- 19396527
TI  - Fragmented maternal sleep is more strongly correlated with depressive symptoms
      than infant temperament at three months postpartum.
AB  - To determine the contribution of infant temperament to the relationship between
      maternal sleep disturbance and depressive symptoms. Utilizing a repeated measures
      design, 112 couples recruited from childbirth education classes were assessed in
      third trimester and postpartum. Instruments included Center for Epidemiologic
      Studies Depression Scale, General Sleep Disturbance Scale, wrist actigraphy, and
      an investigator-developed tool to assess infant temperament completed by mothers
      and fathers. Regardless of infant temperament, mothers who slept < 4 h between
      midnight and 6 am and mothers who napped < 60 min during the day were at
      increased risk for depression at three months postpartum. Infant temperament was
      associated with maternal sleep but was not a significant predictor of depressive
      symptoms after controlling for other contextual factors. Postpartum clinical
      visits should include questions about maternal sleep so interventions can be
      directed toward sufficient sleep to minimize risk of postpartum depression.

PMID- 19396529
TI  - Validation study of a distress screener.
AB  - OBJECTIVES: A 3-item screening instrument called the Distress Screener was
      developed for early identification of distress among employees on sick leave. The
      Distress Screener consists of three items obtained from the distress subscale of
      the four-dimensional symptom questionnaire (4DSQ). This study assessed an optimal
      cut-off point and validated the Distress Screener by relating it to the 4DSQ and
      to medical diagnoses. METHODS: 171 sick-listed employees filled in the Distress
      Screener and the 4DSQ (containing four subscales: distress, depression, anxiety
      and somatisation) and medical diagnoses were obtained from occupational
      physicians (OPs). The optimal cut-off point was assessed by computing sensitivity
      and specificity values. Validity was assessed by relating the Distress Screener
      score to the scores on 4DSQ subscales. In addition scores were compared to mental
      health medical diagnoses and the degree of similarity between two repeated
      measurements was obtained. RESULTS: Using the 4DSQ distress score >10 as
      reference standard, the optimal cut-off point of the Distress Screener was > or
      =4. Regarding validity, a high correlation (0.82) existed between the Distress
      Screener and the 4DSQ distress subscale and it was significantly different from
      the correlations with the other 4DSQ subscales. Also a high correlation existed
      for the test-retest reliability (0.83). Furthermore, a high score on the Distress
      Screener seemed to be related to the medical diagnosis 'Stress-related
      complaints'. All low scores seemed to be related to the medical diagnosis 'Other
      complaints'. Sensitivity (0.85) and specificity (0.78) values, and positive and
      negative predictive values of the screener were comparable to those of the 4DSQ
      distress subscale. CONCLUSIONS: The Distress Screener is a valid instrument for
      use by the OP during consulting time as a quick scan for early identification of
      distress in employees on sick leave. The cut-off point > or =4 is useful for
      early identification of distress in employees on sick leave.

PMID- 19396530
TI  - Synthesis, characterization, DNA-binding and antiproliferative activity of
      Nd(III) complexes with N-(nitrogen heterocyclic) norcantharidin acylamide acid.
AB  - Three novel complexes [Nd(L)(NO3)(H2O)2].NO(3).2H2O (HL1 = N-pyrimidine
      norcantharidin acylamide acid, C12H13N3O4; HL2 = N-pyridine norcantharidin
      acylamide acid, C13H14N2O4; HL3 = N-phenyl norcantharidin acylamide acid,
      C14H15NO4) were synthesized. HL1, HL2 and HL3 are the ligand of complex(1),
      complex(2) and complex(3), respectively. Their structures were characterized by
      elemental analysis, conductivity measurement, infrared spectra and
      thermogravimetric analysis. The DNA-binding properties of the complexes have been
      investigated by fluorescence spectroscopy and viscosity measurements. The results
      suggest that the complexes can bind to DNA by partial intercalation. The liner
      Stern-Volmer quenching constant Ksq values are 3.3(+/-0.21)(1), 1.7(+/-0.19)(2)
      and 0.9(+/-0.04)(3), respectively. Complex (1) and (2) have been found to cleave
      pBR322 plasmid DNA at physiological pH and temperature. The test of
      antiproliferation activity indicates that complex(1) has strong antiproliferative
      ability against the SMMC7721 (IC50 = 131.7 +/- 23.4 micromol x L(-1)) and A549
      (IC50 = 128.4 +/- 19.9 micromol x L(-1)) cell lines. The inhibition rates of
      complex(2) (IC50 = 86.3 +/- 11.3 micromol x L(-1)) are much higher than that of
      NCTD (IC50 = 115.5 +/- 9.5 micromol x L(-1)) and HL2 (111.0 +/- 5.7 micromol x L(
      1)) against SMMC7721 cell lines.

PMID- 19396528
TI  - Transforming growth factor-(beta)s and mammary gland involution; functional roles
      and implications for cancer progression.
AB  - During rodent mammary gland involution there is a dramatic increase in the
      expression of the transforming growth factor-beta isoform, TGF-beta3. The TGF
      betas are multifunctional cytokines which play important roles in wound healing
      and in carcinogenesis. The responses that are activated in the remodeling of the
      gland during involution have many similarities with the wound healing process and
      have been postulated to generate a mammary stroma that provides a
      microenvironment favoring tumor progression. In this review we will discuss the
      putative role of TGF-beta during involution, as well as its effects on the
      mammary microenvironment and possible implications for pregnancy-associated
      tumorigenesis.

PMID- 19396531
TI  - Synthesis and spectroscopic studies of 3,6-diphenyl-2,5-dihydropyrrolo[3,4
      c]pyrrole-1,4-dion's N,N'-dialkyl derivatives.
AB  - 3,6-diaryl-2,5-dihydro-1,4-diketopyrrolo[3,4-c]pyrrole-1,4-dione (DPPD)
      derivatives are used commercially as red pigments, because of their color
      strength, brightness, and very low solubility in most common solvents. These
      products, although highly colored, appear to be of limited value as dyes, since
      they show a tendency to form an aggregate when incorporated into a solvent.
      Monoalkyl and dialkyl derivatives of DPPD were synthesized and then characterized
      with IR, 1HNMR, UV-Vis absorption and emission spectroscopy. Molar absorption
      coefficient, singlet energy level and Stokes' shift values of DPPD derivatives
      were declared. Monoalkyl and dialkyl derivatives of DPPD's solubilities were
      measured from saturated solutions of dimethylformamide (DMF), tetrahydrofuran
      (THF), dichloromethane (DCM), acetonitrile (ACN) and toluene and they are
      compared with each other.

PMID- 19396532
TI  - Triggering receptor in myeloid cells (TREM-1) specific expression in peripheral
      blood mononuclear cells of sepsis patients with acute cholangitis.
AB  - To determine its relationship with acute cholangitis (AC), we sought to quantify
      expression of triggering receptor expressed on myeloid cells (TREM-1) in
      peripheral blood mononuclear cells (PBMC) of sepsis patients with AC. Peripheral
      blood samples of 42 AC patients and 48 patients with AC of severe type (ACST)
      were collected from January to September, 2008 and tested for TREM-1 mRNA by RT
      PCR and protein expression by immunocytochemistry and Western blotting. ELISA and
      immunoturbidimetry were employed to detect the changes of TNF-alpha or C-reactive
      protein in the serum respectively. TREM-1 expression was higher in ACST group
      than in AC group (P < 0.01). TREM-1 was positive in mononuclear cells by
      immunochemistry in both groups before operative therapy, but the positive
      expression rate decreased at 48 h postoperatively. Compared with healthy
      controls, TREM-1 protein expression levels were up-regulated in sepsis patients
      with AC. TREM-1 expression has highly sensitivity and specificity in sepsis
      patients with AC or ACST. TREM-1 is up-regulated in PBMC of AC patients, and has
      higher sensitivity and specificity than other clinical inflammation markers,
      suggesting its importance in AC-induced sepsis.

PMID- 19396533
TI  - The response to fish oil in patients with heart disease depends on the
      predominant arrhythmia mechanism.

PMID- 19396534
TI  - An integrative dynamic model of brain energy metabolism using in vivo
      neurochemical measurements.
AB  - An integrative, systems approach to the modelling of brain energy metabolism is
      presented. Mechanisms such as glutamate cycling between neurons and astrocytes
      and glycogen storage in astrocytes have been implemented. A unique feature of the
      model is its calibration using in vivo data of brain glucose and lactate from
      freely moving rats under various stimuli. The model has been used to perform
      simulated perturbation experiments that show that glycogen breakdown in
      astrocytes is significantly activated during sensory (tail pinch) stimulation.
      This mechanism provides an additional input of energy substrate during high
      consumption phases. By way of validation, data from the perfusion of 50 microM
      propranolol in the rat brain was compared with the model outputs. Propranolol
      affects the glucose dynamics during stimulation, and this was accurately
      reproduced in the model by a reduction in the glycogen breakdown in astrocytes.
      The model's predictive capacity was verified by using data from a sensory
      stimulation (restraint) that was not used for model calibration. Finally, a
      sensitivity analysis was conducted on the model parameters, this showed that the
      control of energy metabolism and transport processes are critical in the
      metabolic behaviour of cerebral tissue.

PMID- 19396535
TI  - Using the Autism-spectrum quotient to discriminate Autism Spectrum Disorder from
      ADHD in adult patients with and without comorbid Substance Use Disorder.
AB  - It is unknown whether the Autism-spectrum quotient (AQ) can discriminate between
      Autism Spectrum Disorder (ASD) and Attention Deficit and Hyperactivity Disorder
      (ADHD) with or without comorbid Substance Use Disorder (SUD). ANOVA's were used
      to analyse the mean AQ (sub)scores of 129 adults with ASD or ADHD. We applied
      receiver operating characteristic (ROC) computations to assess discriminant
      power. All but one of the mean AQ (sub)scores were significantly higher for
      adults with ASD compared to those with ADHD. The SUD status in general was not
      significantly associated with AQ (sub)scores. On the Social Skills subscale
      patients with ASD and comorbid SUD showed less impairment than those without SUD.
      The cut-off score 26 yielded 73% correct classifications. The clinical use of the
      AQ in differentiating between ASD and ADHD is limited.

PMID- 19396536
TI  - Generativity abilities predict communication deficits but not repetitive
      behaviors in Autism Spectrum Disorders.
AB  - Individuals with Autism Spectrum Disorders (ASD) often demonstrate impaired
      generativity that is thought to mediate repetitive behaviors in autism (Turner in
      J Child Psychol Psychiatry, 40(6):839-849, 1999a). The present study evaluated
      generativity in children with and without ASD via the use-of-objects task (Turner
      in J Child Psychol Psychiatry, 40(2):189-201, 1999b) and an Animals Fluency Task
      (Lezak in Neuropsychological assessment. Oxford University Press, Oxford, 1995).
      Groups differed significantly on two of four metrics from the Animals Fluency
      Task and two of seven metrics from the Use of Objects task. In the ASD sample, no
      significant relations were found between generativity and repetitive behaviors.
      Significant relations were found, however, between performance on the Animals
      Fluency Task and communication symptoms. Results replicate reports of
      generativity deficits in ASD and suggest that impaired generativity may reflect
      communication deficits that are characteristic of the disorder.

PMID- 19396537
TI  - Migration, mobility and sexual risk behavior in Mumbai, India: mobile men with
      non-residential wife show increased risk.
AB  - This paper examines the relationship of migration and mobility of husband and
      wife to sexual risk behaviors among married men living in economically marginal
      communities in Mumbai, India. Non-migrant men reported significantly more often
      than the migrant men that they had one or more sex partners other than their
      wives in the last year. Further, men with occupational mobility reported
      significantly more often than the men who were not mobile that they had one or
      more non-spousal sexual partners in the last 1 year. Married men living in Mumbai
      with wives residing in their area of origin and who reported occupational
      mobility had the highest sexual risk behaviors, controlling for socio-demographic
      characteristics and migration. Interventions aimed at prevention of HIV among men
      require special focus on both migrant and non-migrant men with greater
      occupational mobility, with particular emphasis on migrant men whose wives have
      remained in their pre-migration home areas.

PMID- 19396538
TI  - Evaluating the equivalence of clomiphene citrate with and without metformin in
      ovulation induction in PCOS patients.
AB  - OBJECTIVE: To evaluate the benefit of Metformin added to Clomiphene Citrate in a
      primary ovulation induction protocol in PCOS patients. DESIGN: Prospective
      randomised controlled study. SETTING: Tygerberg Academic Hospital, Stellenbosch
      University and the Institute of Reproductive Medicine at Vincent Pallotti
      Hospital, Cape Town. PATIENTS: 107 patients presenting with PCOS. STUDY: Group A
      was pre-treated with metformin 850 mg twice a day for at least 6 weeks before
      clomiphene was added and the metformin was used throughout the study period.
      Group B received clomiphene without pre-treatment with metformin. In both groups
      clomiphene was given at a starting dose of 50 mg day 4-8 and increase with
      increments of 50 mg to a maximum of 150 mg if no response was achieved. RESULTS:
      The ovulation rate achieved in women in the M+C/C arm was 34/52 (65.4%) compared
      to 36/55 (65.5%) in the C/C arm. The treatment effect ((M+C/C) - C/C) is 0% with
      95% confidence interval of -18.1% to 18%. The per protocol ovulation results were
      34/42 (81%) in the M+C/C arm compared to 36/48 (75%) in the C/C arm. The
      ovulation rate difference was 6% with 95% confidence interval -11% to 22%. In a
      comparison of successful ovulating versus non-ovulating women from the trial the
      following were significant baseline determinants: lower median weight in the
      ovulating group (77 kg versus 86 kg, p = .021), lower median bmi (29.0 versus
      32.9, p = .009), lower median DHEAS at baseline (4.6 compared to 7.0, p = .049),
      lower median 17OH-progesterone (2.2 versus 4.6, p = .027) and higher baseline
      median SHBG ( 37.8 compared to 28.5, p = .036). CONCLUSION: Although identical
      ovulation rates were observed in both arms equivalence could not be concluded
      with respect to the specified criteria.

PMID- 19396539
TI  - The selective vulnerability of retinal ganglion cells in rat chronic ocular
      hypertension model at early phase.
AB  - Glutamate neurotoxicity has been postulated to play a prominent role in glaucoma.
      In this study the possible roles of two subunits of glutamate receptors during
      the early phase of retinal ganglion cell (RGC) loss in a rat chronic ocular
      hypertension (COH) model were investigated. COH was induced by applying argon
      laser to the episcleral and limbal veins of the right eye of rats, the
      observation times were at 4, 14 and 28 days after the first laser. RGCs were
      retrogradely labeled by putting Fluoro-Gold (FG) on the surface of both side
      superior colliculus. Immunohistochemical staining using specific antibodies
      against N-methyl-D-aspartate receptor 1 (NR1) or glutamate receptor 2/3 (GluR2/3)
      was performed on the retinal sections of normal and COH eyes. Fluorescent images
      were captured using confocal laser scanning microscope and the number of NR1 and
      GluR2/3 labeled cells were counted and cell size was measured using Stereo
      Investigator. During the observation period, the numbers of NR1 and GluR2/3
      positive RGCs in the RGC layer were reduced parallel to the loss of RGC. The
      dramatic loss of GluR2/3 immunoreactive neurons occurred starting immediately
      after the first laser to 4 days while the dramatic loss of NR1 immunoreactive
      neurons occurred from 14 to 28 days after the first laser. Size difference was
      detected in NR1 immunoreactive RGCs, large ones were more sensitive to the high
      ocular pressure. These results suggest that both NR1 and GluR2/3 are involved in
      the mediation of RGC death in the early stage of COH.

PMID- 19396540
TI  - The effects of respiratory sinus arrhythmia biofeedback on heart rate variability
      and posttraumatic stress disorder symptoms: a pilot study.
AB  - Recent studies have found a significant association between PTSD and low heart
      rate variability (HRV), a biomarker of autonomic dysregulation. Research
      indicates that respiratory sinus arrhythmia (RSA) biofeedback increases HRV while
      reducing related pathological symptoms. This controlled pilot study compared RSA
      biofeedback to progressive muscle relaxation (PMR) as adjunctive interventions
      for 38 persons with PTSD symptoms in a residential treatment facility for a
      substance use disorder. Both groups were assessed at pre-intervention and 4-week
      post-intervention. Group x time interactions revealed significantly greater
      reductions in depressive symptoms and increases in HRV indices for the RSA group.
      Both groups significantly reduced PTSD and insomnia symptoms and a statistical
      trend was observed for reduced substance craving for the RSA group. Increases in
      HRV were significantly associated with PTSD symptom reduction. Overall, these
      results provide preliminary support for the efficacy of RSA biofeedback in
      improving physiological and psychological health for individuals with PTSD.

PMID- 19396541
TI  - Low-vision rehabilitation by means of MP-1 biofeedback examination in patients
      with different macular diseases: a pilot study.
AB  - Macular disease is one of the main causes of visual impairment. We studied the
      efficacy of low-vision rehabilitation by means of MP-1 biofeedback examination in
      patients with different macular disease. Five patients were enrolled (3 female
      and 2 male, mean age 53.8 years) and a total of 9 eyes was examined: 2 eyes with
      vitelliform dystrophy, 1 with a post-traumatic macular scar, 2 with Stargardt
      disease, 2 with myopic macular degeneration, 2 with cone dystrophy. All the
      patients underwent the following tests: visual acuity, reading speed, fixation
      test, MP-1 microperimetry. Low-vision rehabilitation, which lasted 10 weeks,
      consisted of 10 training sessions of 10 min for each eye, performed once a week
      using the MP-1 biofeedback examination. Statistical analysis was performed using
      Student's t-test. p values less than 0.05 were considered statistically
      significant. After training all patients displayed an improvement in visual
      acuity, fixation behaviour, retinal sensitivity and reading speed. Fixation
      behaviour within the 2 degrees diameter circle improved and was statistically
      significant for reading speed (p = 0.01). Reading speed improved from a mean
      value of 64.3 to 92 words/min. Our results show that audio feedback can, by
      increasing attentional modulation, help the brain to fix the final preferred
      retinal locus. Audio feedback facilitates stimuli transmission between
      intraretinal neurons as well as between the retina and brain, which is where the
      highest level of stimuli processing occurs, thereby probably supporting a
      "remapping phenomenon".

PMID- 19396542
TI  - Chronic exposure to pentavalent arsenic of larval leopard frogs (Rana pipiens):
      bioaccumulation and reduced swimming performance.
AB  - Arsenic (As) is mainly released to the environment from anthropogenic sources,
      with inorganic pentavalent As (As [V]) predominant in surface water. In this
      study, Rana pipiens were exposed to As (V) in water at environmentally relevant
      concentrations (control, 10, 20, 150, 500, and 1,000 microg l(-1)) in a static
      renewal system from post-hatch stage through metamorphosis for 113 days. There
      was no significant effect of As exposure on tadpole survival, growth, and percent
      metamorphosis. Maximum swimming speed was significantly slower in the As-treated
      groups compared with the control. During the period of tail resorption (Gosner
      stage 42-46), no significant differences in age at metamorphosis, survival,
      length of tail resorption period, snout-vent length of metamorphs, and sex ratio
      were found among treatments. Whole body As concentrations ranged from <0.6 to
      5.31 mg kg(-1) dry mass, and were significantly higher in the 150, 500, and 1,000
      microg l(-1) treatments than the control. Based on our data, larval tissue
      concentrations of As close to that reported in previous field studies were not
      associated with any significant effects except decreased tadpole swimming speed.

PMID- 19396543
TI  - Valve movement response of the freshwater clam Corbicula fluminea following
      exposure to waterborne arsenic.
AB  - We developed an inductance-based valvometry technique as a detection system to
      measure the valve daily activity in freshwater clam Corbicula fluminea in
      response to waterborne arsenic. Our findings reveal that C. fluminea experiences
      a valve opening in the absence of arsenic predominantly in the morning hours
      (03:00-08:00) with a mean daily opening/closing period of 21.32 (95% CI: 20.58
      22.05) h. Amplification of daily activity occurred in the presence of arsenic.
      Behavioral toxicity assays revealed arsenic detection thresholds of 0.60 (95% CI:
      0.53-0.66) mg l(-1) and 0.35 (95% CI: 0.30-0.40) mg l(-1) for response times of
      60 and 300 min, respectively. The proposed valve daily activity model was linked
      with response time-specific Hill dose-response functions to predict valve
      opening/closing behavior in response to arsenic. The predictive capabilities were
      verified satisfactory with the measurements. Our results implicate a
      biomonitoring system by valve daily activity in C. fluminea to identify safe
      water uses in areas with elevated arsenic.

PMID- 19396544
TI  - Multivariate modeling of chromium-induced oxidative stress and biochemical
      changes in plants of Pistia stratiotes L.
AB  - Biochemical changes in the plants of Pistia stratiotes L., a free floating
      macrophyte exposed to different concentrations of hexavalent chromium (0, 10, 40,
      60, 80 and 160 microM) for 48, 96 and 144 h were studied. Chromium-induced
      oxidative stress in macrophyte was investigated using the multivariate modeling
      approaches. Cluster analysis rendered two fairly distinct clusters (roots and
      shoots) of similar characteristics in terms of their biochemical responses.
      Discriminant analysis identified ascorbate peroxidase (APX) as discriminating
      variable between the root and shoot tissues. Principal components analysis
      results suggested that malondialdehyde (MDA), superoxide dismutase (SOD), APX,
      non-protein thiols (NP-SH), cysteine, ascorbic acid, and Cr-accumulation are
      dominant in root tissues, whereas, protein and guaiacol peroxidase (GPX) in
      shoots of the plant. Discriminant partial least squares analysis results further
      confirmed that MDA, SOD, NP-SH, cysteine, GPX, APX, ascorbic acid and Cr
      accumulation dominated in the root tissues, while protein in the shoot. Three-way
      analysis helped in visualizing simultaneous influence of metal concentration and
      exposure duration on biochemical variables in plant tissues. The multivariate
      approaches, thus, allowed for the interpretation of the induced biochemical
      changes in the plant tissues exposed to chromium, which otherwise using the
      conventional approaches is difficult.

PMID- 19396545
TI  - Identifying persons at risk for PTSD after trauma with TSQ in the Netherlands.
AB  - In The Netherlands about 80% of the population experience a traumatic event while
      about 14% develop post traumatic stress disorder (PTSD). Considering this high
      prevalence the prevention or early treatment of posttraumatic stress is important
      from a health as well as cost-benefit perspective. The aim of this study was to
      examine whether we could identify subjects at risk of developing PTSD. We
      included 100 Dutch victims of different civil traumas that contacted the Victim
      Support Foundation. The trauma screening questionnaire (TSQ), was used as a
      screening tool. The results show that a cut-off score of 7 on the TSQ correctly
      identified most subjects with PTSD. We found a moderate positive correlation
      between PTSD and the severity of complaints. We also found a significant
      relationship between the TSQ and depression symptoms. This study indicates that
      the Dutch version of the TSQ is a useful instrument for identifying future cases
      of PTSD.

PMID- 19396546
TI  - Associations between past alcohol, cannabis, and cocaine use and current
      schizotypy among first-degree relatives of patients with schizophrenia and non
      psychiatric controls.
AB  - Associations between past use of alcohol, cannabis, and cocaine and various
      domains of schizotypy were examined in first-degree relatives of patients with
      schizophrenia and non-psychiatric controls. Substance use was operationalized in
      three ways: (1) having ever used the substance, (2) age at first use, and (3)
      past frequency/amount of use during three time periods in late adolescence/early
      adulthood. Schizotypy was assessed using the Schizotypal Personality
      Questionnaire (SPQ). Participants who had ever used cannabis had significantly
      higher cognitive-perceptual, interpersonal, and total schizotypy scores compared
      to those who had not. Younger age of alcohol use onset was associated with more
      schizotypy in adulthood, and younger age of first cannabis use was related to
      more interpersonal schizotypy. More frequent/heavier use of alcohol in the 25-29
      age-range, and cannabis in early adulthood, were associated with more schizotypy.
      The use of addictive substances, particularly cannabis, is related to schizotypy
      in complex ways.

PMID- 19396547
TI  - Being hopeful and continuing to move ahead: religious coping in Iranian chemical
      warfare poisoned veterans, a qualitative study.
AB  - There is a substantial number of Iranian war veterans, exposed to sulfur mustard,
      who suffer from serious long term progressive health problems involving their
      respiratory organs, eyes, and skin. Little is known, however, about these
      casualties' experiences of living with the consequences of sulfur mustard
      poisoning. This qualitative study aims to provide greater insight into how war
      veterans live with the consequences of the poisoning and involved 17 Iranian war
      veterans who had been poisoned by sulfur mustard during the Iran-Iraq conflict.
      Each participant was interviewed using a semi-structured interview schedule and
      the data generated through this process was analyzed using constant comparative
      data analysis technique. Data analysis resulted in "religious beliefs and
      practices" as a main category, which included two sub-categories: religious value
      centered life and religious support. Findings suggest that religious belief
      assists veterans to accept the impact of poisoning on their lives and adapt their
      lifestyles accordingly, to participate in religious social activities and feel
      socially supported, and to be hopeful about the future and live their lives as
      fully as possible.

PMID- 19396548
TI  - A passive MEMS drug delivery pump for treatment of ocular diseases.
AB  - An implantable manually-actuated drug delivery device, consisting of a refillable
      drug reservoir, flexible cannula, check valve, and suture tabs, was investigated
      as a new approach for delivering pharmaceuticals to treat chronic ocular
      diseases. Devices are fabricated by molding and bonding three structured layers
      of polydimethylsiloxane. A 30 gauge non-coring needle was used to refill the
      reservoir; this size maximized the number of repeated refills while minimizing
      damage to the reservoir. The check valve cracking pressure was 76 +/- 8.5 mmHg
      (mean +/- SE, n = 4); the valve sustained > 2000 mmHg of reverse pressure without
      leakage. Constant delivery at 1.57 +/- 0.2 microL/sec and 0.61 +/- 0.2 microL/sec
      (mean +/- SE, n = 4) under 500 mmHg and 250 mmHg of applied pressure,
      respectively, was obtained in benchtop experiments. The valve closing time
      constant was 10.2 s for 500 mmHg and 14.2 s for 250 mmHg. Assembled devices were
      successfully demonstrated in benchtop, ex vivo, and in vivo experiments.

PMID- 19396549
TI  - Problem-solving style and adaptation in breast cancer survivors: a prospective
      analysis.
AB  - INTRODUCTION: Emotional care of the breast cancer patient is not well understood;
      this lack of understanding results in both a high cost to the patient, as well as
      the health care system. This study examined the role of problem-solving style as
      a predictor of emotional distress, adjustment to breast cancer, and physical
      function immediately post-surgery and 12 months later. METHODS: The sample
      consisted of 121 women diagnosed with breast cancer and undergoing surgery as a
      primary treatment. The survivors completed a measure of problem-solving style and
      three outcome measures immediately post-surgery, as well as at 1 year later.
      There was a 95.6% retention rate at 1 year. RESULTS: Multiple hierarchical
      regressions revealed, after controlling for patient demographics and stage of
      cancer, that problem-solving style (particularly personal control) was associated
      with emotional distress, adjustment to chronic illness, and physical function
      immediately following surgical intervention. In addition, a more positive problem
      solving style was associated with less emotional distress, but not a better
      adaptation to a chronic illness or physical functioning 12 months later; the
      Personal Control again was the best single predictor of the emotional distress,
      adding 10% of the variance in predicting this outcome. CONCLUSIONS: The utility
      of post-surgery assessment may help identify those in need for problem-solving
      training to improve these outcomes at 1 year. Future studies need to determine
      the impact of interventions tailored to levels of problem-solving styles in
      cancer survivors over time. IMPLICATIONS FOR CANCER SURVIVORS: Understanding the
      role of problem solving style in breast cancer survivors deserves attention as it
      is associated with emotional distress immediately and one year after medical
      intervention. Problem-solving style should be evaluated early, and interventions
      established for those most at risk for emotional distress.

PMID- 19396550
TI  - Effects of fluency, oral language, and executive function on reading
      comprehension performance.
AB  - Reading disability (RD) typically consists of deficits in word reading accuracy
      and/or reading comprehension. While it is well known that word reading accuracy
      deficits lead to comprehension deficits (general reading disability, GRD), less
      is understood about neuropsychological profiles of children who exhibit adequate
      word reading accuracy but nevertheless develop specific reading comprehension
      deficits (S-RCD). Establishing the underlying neuropsychological processes
      associated with different RD types is essential for ultimately understanding core
      neurobiological bases of reading comprehension. To this end, the present study
      investigated isolated and contextual word fluency, oral language, and executive
      function on reading comprehension performance in 56 9- to 14-year-old children
      [21 typically developing (TD), 18 GRD, and 17 S-RCD]. Results indicated that TD
      and S-RCD participants read isolated words at a faster rate than participants
      with GRD; however, both RD groups had contextual word fluency and oral language
      weaknesses. Additionally, S-RCD participants showed prominent weaknesses in
      executive function. Implications for understanding the neuropsychological bases
      for reading comprehension are discussed.

PMID- 19396551
TI  - Degradation of glyphosate and other pesticides by ligninolytic enzymes.
AB  - The ability of pure manganese peroxidase (MnP), laccase, lignin peroxidase (LiP)
      and horseradish peroxidase (HRP) to degrade the widely used herbicide glyphosate
      and other pesticides was studied in separate in vitro assays with addition of
      different mediators. Complete degradation of glyphosate was obtained with MnP,
      MnSO4 and Tween 80, with or without H2O2. In the presence of MnSO4, with or
      without H(2)O(2), MnP also transformed the herbicide, but to a lower rate.
      Laccase degraded glyphosate in the presence of (a) 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulphonic acid) (ABTS), (b) MnSO(4) and Tween 80 and (c)
      ABTS, MnSO4 and Tween 80. The metabolite AMPA was detected in all cases where
      degradation of glyphosate occurred and was not degraded. The LiP was tested alone
      or with MnSO4, Tween 80, veratryl alcohol or H2O2 and in the HRP assay the enzyme
      was added alone or with H2O2 in the reaction mixture. However, these enzymes did
      not degrade glyphosate. Further experiments using MnP together with MnSO4 and
      Tween 80 showed that the enzyme was also able to degrade glyphosate in its
      commercial formulation Roundup Bio. The same enzyme mixture was tested for
      degradation of 22 other pesticides and degradation products present in a mixture
      and all the compounds were transformed, with degradation percentages ranging
      between 20 and 100%. Our results highlight the potential of ligninolytic enzymes
      to degrade pesticides. Moreover, they suggest that the formation of AMPA, the
      main metabolite of glyphosate degradation found in soils, can be a result of the
      activity of lignin-degrading enzymes.

PMID- 19396553
TI  - A poor correlation exists between oscillometric and radial arterial blood
      pressure as measured by the Philips MP90 monitor.
AB  - In anesthesia and critical care, invasive arterial blood pressure monitoring is
      the gold standard against which other methods of monitoring are compared. In this
      assessment of the Philips MP90 monitor, the objective was to determine whether or
      not oscillometric measurements were within the accuracy standards set by the
      Association for the Advancement of Medical Instrumentation (AAMI) and the British
      Hypertension Society (BHS). Three hundred and one invasive and noninvasive paired
      measurements were obtained from eleven adult patients on the neurosurgical
      service at Stanford University Medical Center. Bland-Altman plots were created to
      assess agreement between the two measurement systems. Paired correlation
      analysis, bias and precision calculations were performed. Oscillometric blood
      pressure measurements correlated with arterial measurements yielding Pearson r
      values of 0.68, 0.67 and 0.62 for systolic, diastolic and mean pressures,
      respectively (P < 0.01.) Mean differences with 95% confidence intervals were -3.8
      mmHg +/- 13.6, -2.4 mmHg +/- 10.0, and 4.0 mmHg +/- 13.1 for systolic, diastolic
      and mean pressures, respectively. The mean difference for these measurements was
      <or=5 mmHg as stipulated by the AAMI guidelines, but the standard deviation was
      greater than the 8 mmHg allowed by the AAMI guidelines. When the BHS guidelines
      were applied, the device merited a grade "D" for systolic and mean arterial
      pressure, and a grade "C" for diastolic pressure, with the highest possible grade
      level being "A." There was a poor correlation between noninvasive and invasive
      measurements of arterial blood pressure as measured with a cuff and radial
      arterial cannula using the Philips MP90 monitor. These inaccuracies could lead to
      unnecessary interventions, or lack of appropriate interventions in anesthetic
      management. Further study is needed to specify the absolute inaccuracy of the
      monitor, and to determine if accuracy between the two methods varies with patient
      co-morbidities, surgical procedures, or anesthetic management.

PMID- 19396552
TI  - Plasma homocysteine is adversely associated with glomerular filtration rate in
      asymptomatic black and white young adults: the Bogalusa heart study.
AB  - That plasma homocysteine is elevated markedly in renal dysfunction is well
      recognized. But whether the increased homocysteine is an independent correlate of
      glomerular filtration rate, a marker of renal function, in asymptomatic younger
      individuals is not clear. The aim of this study was to determine the association
      between plasma homocysteine and renal function in a biracial (black-white)
      community-based cohort of asymptomatic young adults. Plasma homocysteine along
      with cardiovascular disease risk factor variables were measured in 805 white and
      330 black subjects, ages 24-44 years, enrolled in the Bogalusa Heart Study.
      Modification of Diet in Renal Disease Study equation was used to calculate the
      estimated glomerular filtration rate (eGFR) from serum creatinine level. Males
      versus females showed higher homocysteine levels (8.83 +/- 3.16 vs. 7.35 +/- 2.84
      micromol/L, p < 0.0001) and lower eGFR (99.1 +/- 17.6 vs. 102.5 +/- 21.0
      mL/min/1.73 m(2), p = 0.024). Whites versus blacks had lower eGFR (97.3 +/- 18.0
      vs. 110.0 +/- 20.6 mL/min/1.73 m(2), p < 0.0001). In a multivariate regression
      analysis that included age, race, sex, body mass index, blood pressure,
      lipoprotein variables, insulin resistance index and homocysteine, white race, age
      and homocysteine, in that order, were independently and negatively associated
      with eGFR. The odds ratio (95% confidence interval) of individuals in the
      homocysteine quintiles II, III, IV and V vs. I for having the risk of impaired
      eGFR defined as <10th percentile was 2.28 (0.95-5.50, p = 0.065), 2.97 (1.24
      7.12, p = 0.015), 3.32 (1.45-7.60, p = 0.005) and 6.99 (3.06-15.94, p < 0.0001),
      respectively. Homocysteine is an independent correlate of renal function in
      asymptomatic black and white young adults.

PMID- 19396555
TI  - Family history of various cancers and pancreatic cancer mortality in a large
      cohort.
AB  - A family history of pancreatic cancer is associated with increased risk of
      pancreatic cancer, but uncertainty remains about the magnitude of this
      association, whether it varies by age or smoking and whether a family history of
      other cancers may also be associated with increased risk. We examined family
      history of 14 cancers and pancreatic cancer mortality among ~1.1 million men and
      women in Cancer Prevention Study-II (CPS-II). CPS-II participants completed a
      questionnaire at enrollment in 1982. During follow-up through 2006, there were
      7,306 pancreatic cancer deaths. A family history of pancreatic cancer in a parent
      or sibling was associated with pancreatic cancer mortality [multivariable
      adjusted rate ratio (RR) = 1.66, 95% confidence interval (CI) 1.43-1.94]. This
      association was stronger among participants aged under 60 (RR = 2.89, 95% CI 1.67
      5.02) than among participants aged 60 or older (RR = 1.61, 95% CI 1.37-1.88).
      Weaker associations were observed for family history of stomach cancer (RR =
      1.23, 95% CI 1.11-1.37), liver cancer (RR = 1.25, 95% CI 1.10-1.43), and
      colorectal cancer (RR = 1.12, 95% CI 1.01-1.23). Results from this large
      prospective study indicate family history of pancreatic cancer is associated with
      a moderate increase in risk of pancreatic cancer, and also identify associations
      with the family history of certain other cancers which may be useful in
      generating hypotheses about shared risk factors.

PMID- 19396556
TI  - Design to monitor trend in abundance and presence of American beaver (Castor
      canadensis) at the national forest scale.
AB  - Wildlife conservationists design monitoring programs to assess population
      dynamics, project future population states, and evaluate the impacts of
      management actions on populations. Because agency mandates and conservation laws
      call for monitoring data to elicit management responses, it is imperative to
      design programs that match the administrative scale for which management
      decisions are made. We describe a program to monitor population trends in
      American beaver (Castor canadensis) on the US Department of Agriculture, Black
      Hills National Forest (BHNF) in southwestern South Dakota and northeastern
      Wyoming, USA. Beaver have been designated as a management indicator species on
      the BHNF because of their association with riparian and aquatic habitats and its
      status as a keystone species. We designed our program to monitor the density of
      beaver food caches (abundance) within sampling units with beaver and the
      proportion of sampling units with beavers present at the scale of a national
      forest. We designated watersheds as sampling units in a stratified random
      sampling design that we developed based on habitat modeling results. Habitat
      modeling indicated that the most suitable beaver habitat was near perennial
      water, near aspen (Populus tremuloides) and willow (Salix spp.), and in low
      gradient streams at lower elevations. Results from the initial monitoring period
      in October 2007 allowed us to assess costs and logistical considerations,
      validate our habitat model, and conduct power analyses to assess whether our
      sampling design could detect the level of declines in beaver stated in the
      monitoring objectives. Beaver food caches were located in 20 of 52 sampled
      watersheds. Monitoring 20 to 25 watersheds with beaver should provide sufficient
      power to detect 15-40% declines in the beaver food cache index as well as a
      twofold decline in the odds of beaver being present in watersheds. Indices of
      abundance, such as the beaver food cache index, provide a practical measure of
      population status to conduct long-term monitoring across broad landscapes such as
      national forests.

PMID- 19396557
TI  - Wildfire seasonality and land use: when do wildfires prefer to burn?
AB  - Because of the increasing anthropogenic fire activity, understanding the role of
      land-use in shaping wildfire regimes has become a major concern. In the last
      decade, an increasing number of studies have been carried out on the relationship
      between land-use and wildfire patterns, in order to identify land-use types where
      fire behaves selectively, showing a marked preference (or avoidance) in terms of
      fire incidence. By contrast, the temporal aspects of the relationship between
      landuse types and wildfire occurrence have received far less attention. The aim
      of this paper is, thus, to analyze the temporal patterns of fire occurrence in
      Sardinia (Italy) during the period 2000-2006 to identify land-use types where
      wildfires occur earlier or later than expected from a random null model. The
      study highlighted a close relationship between the timing of fire occurrence and
      land-cover that is primarily governed by two complementary processes: climatic
      factors that act indirectly on the timing of wildfires determining the spatial
      distribution of land-use types, and human population and human pressure that
      directly influence fire ignition. From a practical viewpoint, understanding the
      temporal trends of wildfires within the different land-use classes can be an
      effective decision-support tool for fire agencies in managing fire risk and for
      producing provisional models of fire behavior under changing climatic scenarios
      and evolving landscapes.

PMID- 19396558
TI  - Application of multivariate statistical techniques in hydrogeochemical studies--a
      case study: Brahmani-Koel River (India).
AB  - This study presents the usefulness of multivariate statistical techniques, such
      as correlation matrix, cluster analysis, and factor analysis, for the evaluation
      and interpretation of complex water quality data sets of Brahmani-Koel river
      along the Rourkela Industrial Complex, India, and the apportionment of pollution
      sources/factors. The correlation study suggests that dissolved heavy metals,
      biochemical oxygen demand (BOD), and chemical oxygen demand (COD) are contributed
      by anthropogenic sources. The results of R-mode factor analyses revealed that
      anthropogenic contributions are responsible for increase in metals of the river
      water, which is mainly responsible for contamination of the river. It also
      reflected that the level of pollution in the river was very high. The factor
      score plot and loading plot have been drawn, which indicate that the polluted
      stations are identified by the heavy metals. The relationships among the stations
      are highlighted by cluster analysis, represented in dendograms to categorize
      different levels of contamination. An attempt has been made to study the degree
      of contamination of the river waters by using a tool like enrichment ratio (ER).
      The ER for heavy metal concentrations concluded that metals like Ni, Co, Cr, and
      Fe are showing high enrichment with respect to global background and metal ions
      like Fe, Mn, Cu, and Zn show high enrichment with respect to local background.

PMID- 19396559
TI  - An assessment of heavy metal contamination in surface sediment using statistical
      analysis.
AB  - The distribution and accumulation of heavy metals in the sediments, especially
      those nearest of wastewater discharges of south of Spain, were investigated.
      Sediment samples from 14 locations were collected and characterised for metal
      content (e.g. Ni, Cu, Zn, Cr, Pb, Mn, Cd and Hg), organic carbon, total nitrogen,
      total phosphorous, n-hexane-extractable material, carbonates and grain size.
      Concentration data were processed using correlation analysis and factor analysis.
      The correlation analysis of concentrations data showed important positive
      correlations among organic carbon, total phosphorus, Cu, Zn, Cd and Hg, otherwise
      weak correlations among Mn, Cr, Ni and CO(3) (2-), indicating that these metals
      have complicated geochemical behaviours. The use of statistical factor analysis
      also confirmed these results. Sediments pollution assessment was carried out
      using geoaccumulation and metal pollution indexes (MPI(8)). The results revealed
      that sediments of Cadiz bay and Sancti Petri channel were uncontaminated with the
      studied metals.

PMID- 19396560
TI  - Cytogenetic effects of nine Helichrysum taxa in human lymphocytes culture.
AB  - Helichrysum Mill. (Asteraceae) species have been used in folk medicine for
      thousands of years in the world. The in vitro cytogenetic effects in human
      lymphocytes of nine Helichrysum taxa used in Turkey folk medicine were
      investigated. Blood samples were obtained from healthy donors, non-smoking
      volunteers, which were incubated and exposed to increasing concentrations of
      methanol extracts of Helichrysum taxa (0.01, 0.05, 0.1, 0.5 and 1 mg/mL). The
      inhibitory effects of H. stoechas (L.) Moench subsp. barrelieri (Ten.) Nyman, H.
      armenium DC. subsp. armenium, H. armenium DC. subsp. araxinum (Kirp.) Takht., H.
      plicatum DC. subsp. plicatum, H. compactum Boiss. and H. artvinense P.H.Davis &
      Kupicha on the mitotic index and replication index indicate that these taxa can
      have genotoxic and mutagenic effects. They should therefore not be used freely in
      alternative medicine although their antiproliferative activity may suggest
      anticarcinogenic properties. Increase effects of H. stoechas subsp. barrelieri,
      H. armenium subsp. armenium, H. armenium subsp. araxinum, H. chasmolycicum
      P.H.Davis, H. plicatum subsp. plicatum, H. compactum and H. artvinense on the
      micronucleus rates showed that these taxa can have genotoxic and carcinogenic
      effects.

PMID- 19396561
TI  - Expression of full-length human pro-urokinase in mammary glands of transgenic
      mice.
AB  - Human pro-urokinase expressed in the mammary glands of transgenic animals is
      quickly activated and converted to urokinase by proteases that are present in the
      milk. Thus, it is nearly impossible to isolate full-sized pro-urokinase from the
      milk of transgenic animals. To solve this problem, we constructed transgenic mice
      that express human pro-urokinase and modified ecotin, which is a potent serine
      protease inhibitor from E. coli, in their mammary glands. The gene encoding
      ecotin was modified so as to enhance its specificity for the human urokinase-type
      plasminogen activator. Co-expression of modified ecotin and human pro-urokinase
      in the mammary glands allows for purification of full-length human pro-urokinase
      from these transgenic mice. The results described here suggest a general way of
      preventing the activation of zymogens that are expressed in the mammary glands of
      transgenic animals by co-expression of a zymogen along with a protease inhibitor.

PMID- 19396562
TI  - The effect of root exudates from two transgenic insect-resistant cotton lines on
      the growth of Fusarium oxysporum.
AB  - The attenuation of disease resistance in transgenic insect-resistant cotton has
      become one of the important factors restricting cotton production in China. Two
      transgenic insect-resistant cotton lines and their parental conventional cotton
      lines were used as the testing materials. The effects of root exudates of these
      cotton lines on the spore germination and mycelial growth of Fusarium oxysporum
      were studied and the components, contents of amino acids and sugars were
      determined. The results showed that the resistance of the two insect-resistant
      cotton lines to F. oxysporum was inferior to the parental lines, and that their
      root exudates promoted fungal spore germination and mycelial growth. Considerable
      differences in the components and contents of both, amino acids and sugars were
      found between the root exudates of transgenic cotton lines and their parental
      lines, where the disease indices were highly correlated with the total amount of
      sugars in the root exudates.

PMID- 19396563
TI  - Financial loss estimation, prevalence and characterization of hydatidosis of
      cattle slaughtered at Debre Markos Municipality abattoir, Ethiopia.

PMID- 19396564
TI  - Milk yield and reproductive performance of dairy cattle under smallholder
      management system in North-eastern Amhara Region, Ethiopia.
AB  - This study was conducted in South Wollo Zone of Amhara Regional State, Ethiopia,
      to assess the milk yield and reproductive performance of indigenous and crossbred
      cattle under smallholder management conditions. Questionnaire survey was used to
      collect retrospective data on the performance of dairy cattle in 186 households.
      Thirty two postpartum cows (16 indigenous and 16 crossbred) were selected
      purposively and monitored for five months and milk samples were collected twice
      per week from each cow to determine postpartum ovarian activity using ELISA
      techniques. Daily milk yields at all stages of lactation were significantly (P <
      0.01) higher in crossbred than indigenous cows. Crossbred cows had significantly
      (P < 0.01) longer lactation length and shorter age at first calving, while
      calving interval was significantly shorter in cows that gave previous calves
      during the wet season than the dry season. Only six cows (18.8%) showed heat
      signs on an average of 136 days postpartum of which one was a crossbred and five
      were indigenous. While, 11 cows (34.3%) resumed ovarian activity until 150(th)
      day postpartum among which three were crossbred and eight were indigenous.

PMID- 19396565
TI  - Dietary folate and vitamin B12 supplementation and consequent vitamin deposition
      in chicken eggs.
AB  - We determined the effects of dietary supplementation with folate and vitamin
      B(12) on lipid metabolism and the deposition of these vitamins in eggs of laying
      hens (age 64-72 weeks). Four levels of folate (0, 0.5, 4 and 10 mg/kg) and three
      levels of vitamin B(12) (0, 0.01 and 0.08 mg/kg) were added to the basal diet for
      8 weeks in a 4 x 3 factorial completely randomized design study. No significant
      physiological interaction between folate and vitamin B(12) was evident under our
      experimental conditions. There was no effect of vitamins supplementation on egg
      production or feed intake. Supplementation with folate significantly elevated
      serum (p < 0.01) and yolk (p < 0.05) folate levels. Supplementation with vitamin
      B(12) did not significantly affect serum or egg yolk vitamin B(12) levels.
      Supplementation with folate or vitamin B(12) did not significantly affect
      triglyceride or total phospholipid levels in serum or egg yolk although a
      positive relationship was observed between dietary folate supplementation and
      total serum phospholipid (r(2) = 0.68, p < 0.05). The study showed that it is
      possible to produce folate-enriched eggs. An increase in serum total
      phospholipids due to dietary supplementation with folate may provide
      physiological benefits to hens, although we did not observe any strong effects of
      these vitamins on lipid composition.

PMID- 19396566
TI  - An in-vivo study of the efficacy and safety of ethno-veterinary remedies used to
      control cattle ticks by rural farmers in the Eastern Cape Province of South
      Africa.
AB  - Ticks feed on blood, are vectors of tick-borne diseases and cause considerable
      skin damage to livestock. They are commonly controlled using commercial
      acaricides, which are expensive to the rural farmers, causing them to resort to
      alternative tick control methods. The objective of this study was to assess the
      acaricidal properties and safety of some materials (Ptaeroxylon obliquum, Aloe
      ferox, Lantana camara, Tagetes minuta, Used engine oil and Jeyes fluid, used by
      rural farmers to control cattle ticks in the Eastern Cape Province, South Africa.
      A total of 52 cattle were divided into 13 experimental groups with 4 cattle in
      each. Jeyes fluid at 76.8% concentration and Used engine oil had an efficacy that
      was almost similar to that of the positive control Ektoban (Cymiazol 17.5 and
      cypermethrin 2.5%). Extracts of L. camara at 40% concentration had an efficacy of
      57% while A. ferox, P. obliquum and T. minuta were not effective. The test
      materials had no irritation effect on rats. The study revealed that the materials
      rural farmers use as acaricides vary in their efficacy in controlling ticks.

PMID- 19396567
TI  - Sodium bicarbonate for the prevention of contrast-induced nephropathy: a meta
      analysis of 17 randomized trials.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) is a common cause of acute kidney
      injury. Several preventive therapies for this injury have been tested; however,
      there is still no consensus on the optimal protocol. METHODS: We performed a
      systematic search of the National Library of Medicine and the Cochrane Library
      databases from January 1985 to November 2008 to identify randomized controlled
      studies examining sodium bicarbonate as a preventive measure for CIN in humans.
      We also reviewed conference abstracts from cardiology nephrology and radiology
      meetings from 2004 to 2008. A change in serum creatinine levels defined by an
      absolute (>or=0.5 mg/dl) or percentage (>or=25%) increase in the serum creatinine
      level is defined as CIN. The primary outcome measure was the incidence of CIN,
      and the secondary outcome measures were: change in serum creatinine from
      baseline, requirement for renal replacement therapy and death. RESULTS: Seventeen
      randomized controlled trials have investigated the role of sodium bicarbonate for
      prophylaxis of CIN. The overall incidence of CIN was 11.3%. Using the results
      from all 17 studies that compared bicarbonate versus saline, the pooled relative
      risk of developing CIN was 0.54 (95% CI, 0.36-0.83) in the intervention arm,
      indicating a significant benefit from sodium bicarbonate. The pooled relative
      risk of CIN was 0.57 (95% CI, 0.35-0.95) when we analyzed for the studies that
      compared the effects sodium bicarbonate to NAC on development of CIN. There was
      no difference in the rates of requirement for renal replacement therapy and
      death. CONCLUSIONS: The use of sodium bicarbonate appears to reduce the incidence
      of CIN when compared to other preventive strategies for CIN without a significant
      difference in the requirement of renal replacement therapy and mortality. There
      are study heterogeneity and publication biases. Further adequately powered
      randomized controlled studies are needed to determine whether sodium bicarbonate
      will reduce the clinically meaningful outcomes (e.g., need for dialysis or death)
      and optimal hydration strategy in high-risk patients.

PMID- 19396568
TI  - The effects of neoadjuvant chemotherapy and chemo-radiation therapy on MRI
      staging in invasive bladder cancer: comparative study based on the pathological
      examination of whole layer bladder wall.
AB  - OBJECTIVE: We evaluated the correlation of radiological findings obtained by MRI
      study with pathological diagnosis in invasive bladder cancer treated with
      neoadjuvant chemotherapy, with or without radiation. DESIGN, SETTING, AND
      PARTICIPANTS: Twenty-seven patients, who underwent total or partial cystectomy
      for invasive bladder tumors, were enrolled into the present study. Eight cases
      had received neoadjuvant chemotherapy following the staging biopsy (group A), ten
      cases had received chemo-radiation therapy following the staging biopsy (group
      B), and nine cases had received preoperative staging biopsy alone (group C). As a
      final treatment, 12 of the 27 patients underwent total cystectomy and the other
      15 patients underwent partial cystectomy. MRI was conducted prior to total or
      partial cystectomy in each case. The pathological stage was assessed by
      histological examination of the entire layer of the bladder wall. RESULTS AND
      LIMITATIONS: Tumor stage assessed by MRI was consistent with pathological
      findings in 16 of the 27 cases (59.3%), while MRI produced over-staging in 7
      cases and under-staging in 4 cases. The accuracy of staging was 75.0, 30.0, and
      77.8% in groups A, B, and C, respectively. The accuracy of MRI staging in group B
      was lower than that in group C (P < 0.05). There was no difference in the
      accuracy of MRI staging between groups A and C. CONCLUSION: MRI is useful for the
      staging of bladder cancer. However, care needs to be taken when staging invasive
      bladder tumors treated with neoadjuvant chemo-radiation therapy, because
      inflammatory infiltrations and/or fibrous changes caused by the chemotherapy or
      chemo-radiation therapy make precise staging with MRI difficult.

PMID- 19396569
TI  - International symposium on pediatric neurotransmitter diseases.

PMID- 19396571
TI  - Infection of barley by Ramularia collo-cygni: scanning electron microscopic
      investigations.
AB  - Ramularia collo-cygni causes leaf spots on barley (Hordeum vulgare), a disease of
      growing economical importance. Scanning electron microscopy was used to study the
      life cycle of the fungus on barley during the vegetation period and in winter.
      The infectious stage started with conidium germination on the surface and the
      penetration into the leaf via the stomatal pore where the hyphae grew within the
      cells that became necrotic. The conidiophores emerged through the stomatal pore.
      On older leaves, however, they frequently emerged apart from it and the results
      suggested a pushing apart of adjacent cell walls of the epidermal cells. An
      assessment of the amount of conidium formation of one heavily infested barley
      plant resulted in 4.05 x 10(6) conidia per plant. For the first time,
      conidiophores, conidium production and germination of conidia were also observed
      in winter on barley and on maize leaves.

PMID- 19396570
TI  - Congenital disorder of glycosylation type Ia: heterogeneity in the clinical
      presentation from multivisceral failure to hyperinsulinaemic hypoglycaemia as
      leading symptoms in three infants with phosphomannomutase deficiency.
AB  - We describe three patients with congenital disorder of glycosylation (CDG) type
      Ia, all of whom had persistent hyperinsulinaemic hypoglycaemia responding to
      diazoxide therapy as a common feature. The first patient, an infant girl,
      presented with recurrent vomiting, failure to thrive, liver impairment,
      hypothyroidism and a pericardial effusion. The second patient, also female, had a
      milder disease with single organ involvement, presenting as isolated
      hyperinsulinaemic hypoglycaemia, not associated with any cognitive impairment.
      The third patient, a boy presented with multi-organ manifestations including
      congenital hypothyroidism, persistent hyperinsulinaemic hypoglycaemia,
      coagulopathy, olivopontocerebellar hypoplasia and recurrent pancreatitis. All
      three patients had a type 1 serum transferrin isoform pattern, and were
      subsequently found to have low phosphomannomutase activity, confirming the
      diagnosis of CDG type Ia. Our findings emphasize that CDG should be considered as
      a differential diagnosis in patients with persistent hyperinsulinaemic
      hypoglycaemia and that it may even occasionally be the leading symptom in CDG Ia.

PMID- 19396572
TI  - Measuring stigma across neurological conditions: the development of the stigma
      scale for chronic illness (SSCI).
AB  - PURPOSE: Most measures of stigma are illness specific and do not allow for
      comparisons across conditions. As part of a study of health-related quality of
      life for people with neurological disorders, our team developed an instrument to
      assess the stigma for people with chronic illnesses. METHODS: We based item
      content on literature review, responses from focus groups, and cognitive
      interviews. We then administered the items to people with neurological disorders
      for psychometric testing. RESULTS: Five hundred eleven participants completed
      items of the stigma scale. Exploratory factor analysis produced two factors that
      were highly correlated (r = 0.81). Confirmatory factor analysis produced high
      standardized loadings on an overall stigma factor (0.68-0.94), with poorer
      loadings on the two sub-domains (-0.12 to 0.53). These results demonstrated a
      sufficiently unidimensional scale that corresponded with the bifactor model. Item
      response theory modeling suggested good model fit, and differential item
      functioning analyses indicated that the 24-item scale showed potential for
      measurement equivalence across conditions. CONCLUSIONS: Our efforts produced a
      stigma scale that had promising psychometric properties. Further study can
      provide additional information about the SSCI and its benefit in measuring the
      impact of stigma across conditions.

PMID- 19396573
TI  - Genetics and mapping of adult plant rust resistance in soybean PI 587886 and PI
      587880A.
AB  - Two soybean accessions, PI 587886 and PI 587880A, previously identified as having
      resistance to Phakospora pachyrhizi Syd. (soybean rust, SBR) were used to create
      two populations (POP-1 and POP-2) segregating for SBR resistance. F(2)-derived
      F(3) (F(2:3)) families from each population were grown in a naturally SBR
      infected field in Paraguay to determine inheritance and map resistance genes.
      Over 6,000 plants from 178 families in POP-1 and over 5,000 plants from 160
      families in POP-2 were evaluated at R5 for lesion type: immune reaction (IR),
      reddish-brown (RB), or tan (TAN) colored lesions. Based on the lesion type
      present, each F(2:3) family was rated as resistant, segregating or susceptible
      and this classification was used to infer the F(2)-phenotype and genotype. For
      both populations, the F(2) segregation ratios fit a 1:2:1
      (resistant:segregating:susceptible) ratio expected for a single gene (P > 0.05).
      The RB lesions occurred almost exclusively in the heterozygous class, indicating
      incomplete dominance under the conditions of this study. Molecular markers
      flanking the locations of the known resistance genes were used to map the
      resistance gene in both populations to the Rpp1 locus. However, evaluation of PI
      587886 and PI 587880A against eight P. pachyrhizi isolates indicated that the
      resistance allele in these two accessions was different from Rpp1. This test also
      demonstrated that these accessions were resistant to at least one P. pachyrhizi
      isolate collected in the southern US. This is the first report of using an adult
      plant field-screen with natural rust pressure to map SBR resistance.

PMID- 19396574
TI  - Should maize doubled haploids be induced among F(1) or F (2) plants?
AB  - Maize (Zea mays L.) doubled haploid lines are typically produced from F(1)
      plants. Studies have suggested that the low frequency of recombinants in doubled
      haploids may reduce the response to selection. My objective was to determine if,
      for sustaining long-term response, doubled haploids should be induced in F(1) or
      F(2) plants during maize inbred development. In simulation experiments, I
      examined the response to multiple cycles of testcross selection among doubled
      haploid lines derived from F(1) plants (denoted by DH), doubled haploid lines
      derived from F(2) plants (DH(F2)), and recombinant inbred (RI) lines derived by
      single-seed descent. For a trait controlled by 100 or more quantitative trait
      loci (QTL), the cumulative responses to selection were up to 4-6% larger among
      DH(F2) lines than among DH lines. The cumulative responses were up to 5-8% larger
      among RI lines than among DH lines. The QTL become unlinked as the number of QTL
      in a finite genome decreases, and the responses among RI, DH, and DH(F2) lines
      were equal or nearly equal when only 20 QTL controlled the trait. Metabolic-flux
      epistasis reduced the differences in the response among RI, DH, and DH(F2) lines.
      Overall, the results indicated that doubled haploids should be induced from F(2)
      plants rather than from F(1) plants. If year-round nurseries are used and new
      F(1) crosses for inbred development are initially created on a speculative basis,
      the development of doubled haploids from F(2) rather than F(1) plants should not
      cause a delay in inbred development.

PMID- 19396575
TI  - Attitudes towards health among patients and staff in mental health services: a
      comparison of ratings of importance of different items of health.
AB  - BACKGROUND: In mental health services, the concept of health is often perceived,
      from a biomedical perspective, as the absence of disease, involving several
      negative consequences together with a lack of systematic health-promoting
      activities. The subjective experiences of health among patients in mental health
      services are crucial to reinforce the experience of health throughout different
      phases of life. Positive dimensions of health include interaction between the
      individual and the environment, subjective experience of individual power as well
      as possibilities to influence important aspects of the life situation. The aim of
      the study was to describe and compare attitudes to health among patients and
      staff in mental health services in terms of the importance of health as measured
      by the attitude version of the Health Questionnaire. METHODS: A cross-sectional
      study including a randomly selected sample of 141 outpatients in contact with the
      mental health services and 140 mental health staff was performed. RESULTS:
      Patients and staff share most attitudes towards health, which indicates that
      health is a concept that applies to human beings irrespective of mental disease
      in the context of mental health services. CONCLUSIONS: The possibility to be able
      to define, measure, and compare positive dimensions of health may be important in
      the attempts to divert the focus towards one that promotes health and resources
      in mental health services and away from one on illness and deficits.

PMID- 19396577
TI  - Characterization of monoclonal antibodies against the nonstructural 5A protein of
      hepatitis C virus.
AB  - The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) is a
      multifunctional protein that leads to pleiotropic responses, in part by
      regulating cell growth and cellular signaling pathways. Here, we produced
      monoclonal antibodies (mAbs) directed against the HCV NS5A protein. The N
      terminal epitope was mapped to amino acids 60-80 of the NS5A protein, and the
      epitope in the middle region was mapped to amino acids 221-236. Because these
      epitopes overlap with binding regions of human vesicle-associated membrane
      protein-associated protein (hVAP)-B and TNF-receptor-associated factor 2 (TRAF2),
      respectively, we investigated these mAbs for their potential capacity to inhibit
      viral and cellular interactions. We found that NS5A and hVAP-B interaction was
      abolished by mAb E5D3, and NS5A and TRAF2 interaction was inhibited by mAb C6D4.
      Since hVAP-B is necessary for HCV replication and TRAF2 is the major transducer
      in TNF signaling cascades, these data may provide further insights into the
      mechanisms underlying HCV replication and viral modulation of host signal
      transduction.

PMID- 19396576
TI  - Ethnicity and dangerousness criteria for court ordered admission to a psychiatric
      hospital.
AB  - BACKGROUND: Black and minority ethnic (BME) populations are disproportionately
      detained in psychiatric hospitals. AIM: To examine the dangerousness criteria for
      compulsory court ordered admission to a psychiatric hospital in White and BME
      persons. METHOD: We examined the psychiatric examinations for court ordered
      compulsory admissions in 506 White and 299 BME persons from October 2004 until
      January 2008 in Rotterdam, the Netherlands. The White and BME groups are compared
      using Chi-square tests and in case of significant differences with logistic
      regression models adjusted for age, gender, mental disorders and socio-economic
      background. RESULTS: In BME persons, violence towards others and neglect of
      relatives were more often reasons to request court order admission as compared
      with Whites (39.8 vs. 25.3%, P < 0.001, respectively, 6.4 vs. 2.4%, P = 0.01).
      This remained true after adjustment for age, gender, mental disorders and socio
      economic background [OR 1.56 (95% CI 1.12-2.18), P = 0.01, respectively; OR 3.08
      (95% CI 1.31-7.26), P = 0.01]. The other reasons for a request of court order
      admission had a similar prevalence in both groups (suicide or self-harm, social
      decline, severe self-neglect, arousal of aggression of others, danger to the
      mental health of others, and the general safety of persons and goods).
      CONCLUSION: Violence towards others and neglect of relatives are more often a
      reason to request court ordered admission in BME than in White persons. BME
      patients are more often perceived as potentially dangerous to others.

PMID- 19396578
TI  - Isolation and molecular characterization of equine H3N8 influenza viruses from
      pigs in China.
AB  - During 2004-2006 swine influenza virus surveillance, two strains of H3N8
      influenza viruses were isolated from pigs in central China. Sequence and
      phylogenetic analyses of eight gene segments revealed that the two swine isolates
      were of equine origin and most closely related to European equine H3N8 influenza
      viruses from the early 1990s. Comparison of hemagglutinin (HA) amino acid
      sequences showed several important substitutions. One substitution caused the
      loss of a potential glycosylation site, and two substitutions, located at the
      cleavage site and adjacent to the receptor-binding pocket, respectively, had been
      reported previously in canine H3 HAs. This expansion of host range of equine H3N8
      influenza viruses with mutations in the HA protein might raise the possibility of
      transmission of these viruses to humans.

PMID- 19396579
TI  - Microleakage and scanning electron microscopy evaluation of all-in-one self-etch
      adhesives and their respective nanocomposites prepared by erbium:yttrium-aluminum
      garnet laser and bur.
AB  - The aim of this study was to evaluate the microleakage of all-in-one self-etch
      adhesives and their respective nanocomposites in class V cavities prepared by
      erbium:yttrium-aluminum-garnet (Er:YAG) laser and bur. Class V cavities were
      prepared on both buccal and lingual surfaces of 72 premolars by Er:YAG laser or
      bur and divided into six groups (n = 24). The occlusal margins were enamel and
      the cervical margins were cementum. The groups were as follows: group 1 Er:YAG
      laser preparation (E) + Xeno V (X) + CeramX (C); group 2 bur preparation (B) + X
      + C; group 3 E + AdheSE One (A) + Tetric EvoCeram (T); group 4 B + A + T; group 5
      E + Clearfil S3 Bond (CSB) + Clearfil Majesty Esthetic (CME); group 6 B + CSB +
      CME. All teeth were stored in distilled water at 37 degrees C for 24 h, then
      thermocycled 500 times (5-55 degrees C). Ten teeth from each group were chosen
      for the microleakage investigation and two teeth for the scanning electron
      microscopy (SEM) evaluation. The teeth that were prepared for the microleakage
      test were immersed in 0.5% basic fuchsin dye for 24 h. After immersion, the teeth
      were sectioned and observed under a stereomicroscope for dye penetration. Data
      were analyzed by Kruskal-Wallis and Mann-Whitney U tests (P < 0.05). Bur-prepared
      cavities presented less microleakage in all groups for enamel (P < 0.05);
      however, in cervical margins, there were no differences between laser-prepared
      and bur-prepared cavities in the Xeno V + CeramX and AdheSE One + Tetric EvoCeram
      groups (P > 0.05). SEM observations of restorative material-dentin interfaces
      seemed to correspond with those of the microleakage test. Microleakage at the
      cervical interfaces was greater than that at the occlusal interfaces. Er:YAG
      laser-prepared class V cavities yielded more microleakage in occlusal margins
      with all-in-one self-etch adhesives and the respective manufacturer's
      nanocomposites.

PMID- 19396580
TI  - The relationship between smoking status and serious psychological distress:
      findings from the 2007 Behavioral Risk Factor Surveillance System.
AB  - OBJECTIVES: To examine the associations between smoking and quit attempts with
      psychological distress and also by socioeconomic groups. METHODS: Using data on
      172,938 adult respondents from the 2007 Behavioral Risk Factor Surveillance
      System we used the Kessler-6 scale to assess psychological distress among never,
      former, some-day, and everyday smokers and smokers attempting to quit. RESULTS:
      Everyday smokers and attempting quitters had higher mean levels of 30-day
      psychological distress than never smokers. Compared with never smokers, the odds
      of having serious psychological distress (SPD) were: former smokers, 1.3 (95 %
      CI: 1.1-1.6); some-day smokers, 2.5 (95 % CI: 2.0-3.1); and everyday smokers, 3.3
      (95 % CI: 2.8-3.8). As for unsuccessful quit attempts, the odds were highest for
      current smokers (3.3 [95 % CI: 2.8-3.8]) versus never smokers. Among current
      smokers, persons with less than high school education, income less than $ 50,000,
      or who were unemployed or unable to work had the highest odds of reporting SPD.
      CONCLUSIONS: Given the association between current smoking behaviors and
      psychological distress, future tobacco prevention and control efforts may benefit
      by including components of mental health, especially for low SES populations.

PMID- 19396581
TI  - Association between diagnosed diabetes and serious psychological distress among
      U.S. adults: the Behavioral Risk Factor Surveillance System, 2007.
AB  - OBJECTIVES: To estimate the prevalence of serious psychological distress (SPD)
      according to diabetes status and to assess the association of diabetes-related
      risks and conditions with SPD among U.S. adults. METHODS: We analyzed data from
      the Behavioral Risk Factor Surveillance System, 2007. SPD was determined by a
      score of > or = 13 on the Kessler-6 scale. We used log-binomial regression
      analysis to estimate prevalence ratios (PRs) and 95 % confidence intervals (CIs).
      RESULTS: We estimated the prevalence of SPD to be 7.6 % and 3.6 % among U.S.
      adults with and without diagnosed diabetes (unadjusted PR: 2.09; 95 % CI: 1.87,
      2.34). The association of diagnosed diabetes with SPD was attenuated after
      adjustments for potential confounding effects of cardiovascular risk factors and
      cardiovascular comorbid conditions (adjusted PR, 1.12; 95 % CI: 0.99, 1.27).
      Significant correlates of SPD among persons with diagnosed diabetes were young
      age, low education levels, low household income, obesity, current smoking, no
      leisure-time physical activity, presence of one or more micro- or macro-vascular
      complications, and disability. CONCLUSIONS: The crude prevalence of SPD among
      adults with diagnosed diabetes was twice as high as that among those without
      diabetes. The increased prevalence of SPD may be accounted for by the excessive
      rates of cardiovascular risks and comorbid conditions among people with diagnosed
      diabetes.

PMID- 19396582
TI  - Integrating mental health care with chronic diseases in low-resource settings.

PMID- 19396583
TI  - Modifiable characteristics of a healthy lifestyle and chronic health conditions
      in older adults with or without serious psychological distress, 2007 Behavioral
      Risk Factor Surveillance System.
AB  - OBJECTIVE: The associations between serious psychological distress (SPD), chronic
      health conditions, healthy behaviors, healthy weight, and use of preventive
      services were examined among adults 65 years old and older using the 2007
      Behavioral Risk Factor Surveillance System (BRFSS). METHODS: Participants (N =
      35,845) completed a scale of nonspecific psychological distress for the past 30
      days. Chronic health conditions were investigated in addition to having a healthy
      weight (body mass index 18.5-24.9 kg/m(2)), not smoking, consuming < or = 1
      alcoholic beverage per day, consuming at least five fruits or vegetables daily,
      participating in moderate-to-vigorous physical activity during the average week,
      receiving an annual influenza immunization, and ever receiving a pneumococcal
      immunization. RESULTS: People with SPD were more likely than those without SPD to
      report chronic health conditions and less likely to be nonsmokers. No differences
      were found for the remaining healthy behaviors, healthy body weight, and use of
      preventive services. CONCLUSIONS: Older adults with SPD have a similar pattern of
      engagement in health behaviors, healthy weight, and use of preventive services
      compared to those without SPD despite reporting worse health status and presence
      of multiple chronic health conditions.

PMID- 19396584
TI  - Synergistic effects of ovine-derived cathelicidins and other antimicrobials
      against Escherichia coli O157:H7 and Staphylococcus aureus 1056 MRSA.
AB  - Synergistic effects of ovine-derived cathelicidins SMAP29 and OaBac5mini with the
      antimicrobials polymyxin B, lysozyme, nisin and lactoferrin were investigated
      against E. coli O157:H7 and S. aureus 1056 MRSA. Lysozyme showed synergy against
      E. coli O157:H7 with SMAP29, polymyxin B and lactoferrin. Synergy was also found
      between SMAP29 and lactoferrin against this host. Against S. aureus 1056 MRSA,
      lysozyme showed synergy with OaBac5mini, polymyxin B and nisin, while synergy was
      also found between nisin and OaBac5mini and polymyxin B. Other combinations of
      the antimicrobials were either additive or non-synergistic.

PMID- 19396585
TI  - SAM levels, gene expression of SAM synthetase, methionine synthase and ACC
      oxidase, and ethylene emission from N. suaveolens flowers.
AB  - S'adenosyl-L: -methionine (SAM) is a ubiquitous methyl donor and a precursor in
      the biosynthesis of ethylene, polyamines, biotin, and nicotianamine in plants.
      Only limited information is available regarding its synthesis (SAM cycle) and its
      concentrations in plant tissues. The SAM concentrations in flowers of Nicotiana
      suaveolens were determined during day/night cycles and found to fluctuate
      rhythmically between 10 and 50 nmol g(-1) fresh weight. Troughs of SAM levels
      were measured in the evening and night, which corresponds to the time when the
      major floral scent compound, methyl benzoate, is synthesized by a SAM dependent
      methyltransferase (NsBSMT) and when this enzyme possesses its highest activity.
      The SAM synthetase (NsSAMS1) and methionine synthase (NsMS1) are enzymes, among
      others, which are involved in the synthesis and regeneration of SAM. Respective
      genes were isolated from a N. suaveolens petal cDNA library. Transcript
      accumulation patterns of both SAM regenerating enzymes matched perfectly those of
      the bifunctional NsBSMT; maximum mRNA accumulations of NsMS1 and NsSAMS1 were
      attained in the evening. Ethylene, which is synthesized from SAM, reached only
      low levels of 1-2 ppbv in N. suaveolens flowers. It is emitted in a burst at the
      end of the life span of the flowers, which correlates with the increased
      expression of the 1-aminocyclopropane-1-carboxylate oxidase (NsACO).

PMID- 19396586
TI  - Spontaneous recanalization of a completely occluded saphenous vein graft two
      months following acute myocardial infarction with persistent one year patency.
AB  - Acute myocardial infarction resulting from saphenous vein graft occlusion occurs
      not infrequently in patients who have undergone coronary artery bypass graft
      surgery. In this case report, we present a novel case of spontaneous
      recanalization of a thrombotic graft occlusion in a patient who presented with a
      subacute myocardial infarction. The patient was treated medically with aspirin as
      the only anti-platelet agent. Interestingly, he presented 2 months later with new
      onset angina. Coronary angiography demonstrated complete resolution of thrombus
      but a severe focal stenosis in the distal anastomoses. Following drug eluting
      stent placement, a favorable clinical course has ensued and patency confirmed on
      follow up angiography at 1 year.

PMID- 19396587
TI  - Genomic characterization of swine caliciviruses representing a new genus of
      Caliciviridae.
AB  - This study reports the molecular characterization of novel caliciviruses, the St
      Valerien-like viruses, which were isolated from pig feces in the province of
      Quebec, Canada between 2005 and 2007. The genomes of St-Valerien-like viruses
      contain 6409 nucleotides and include two main open reading frames (ORFs). ORF1
      encodes the non structural (NS) polyprotein and the major capsid protein (VP1)
      while ORF2 encodes the putative basic minor capsid protein. Typical conserved
      amino acid motifs predict a gene order reminiscent of calicivirus genomes.
      Phylogenetic, pairwise homology, and distance analyses performed on complete
      genomic sequences and partial amino acid sequences from the NTPase, polymerase,
      and major capsid protein segregated the St-Valerien-like viruses in a unique
      cluster sharing a common root with the Tulane virus and the noroviruses. Based on
      the genomic analyses presented, the St-Valerien-like viruses are members of a new
      genus of Caliciviridae for which we propose the name Valovirus.

PMID- 19396588
TI  - One-step column purification of herpes simplex virus 1 helicase-primase
      subcomplex using C-terminally his-tagged UL5 subunit.
AB  - A protocol for purification of the two-subunit complex of herpes simplex virus
      type 1 (HSV-1) helicase-primase by metal affinity chromatography is presented. In
      order to bind the enzyme complex consisting of UL5 and UL52 gene functions to the
      affinity column, the C-terminus of the UL5 gene of HSV-1 strain ANG was fused in
      frame with a sequence encoding six histidines, resulting in a His6-tagged DNA
      helicase (UL5his) when expressed via recombinant baculovirus. In addition,
      hybridoma cell lines producing anti-UL5 IgG were generated for screening of DNA
      helicase expression. Initial purification trials revealed that the presence of
      low concentrations of imidazole in the wash buffers interfered with the binding
      of the helicase-primase subunit complex to the metal affinity resin. Alternative
      means, such as high salt, altered pH, and substitution of imidazole by histidine
      tetrapeptide (His4), were tested. From those, the addition of His4 in combination
      with an acidic pH turned out to be very efficient for the removal of protein
      contaminants from a Ni2+-NTA (nitrilotriacidic acid) affinity resin. By applying
      only one column step, the present protocol yields a helicase-primase preparation,
      which is suitable for inhibitor screening and further functional studies. The
      final preparation is free of interfering enzyme activities, and exerts each of
      the enzymatic functions described for a two subunit complex, i.e., DNA-dependent
      ATPase, DNA primase, and DNA helicase activities.

PMID- 19396589
TI  - Determination of filbertone in spiked olive oil samples using headspace
      programmed temperature vaporization-gas chromatography-mass spectrometry.
AB  - A sensitive method for the fast analysis of filbertone in spiked olive oil
      samples is presented. The applicability of a headspace (HS) autosampler in
      combination with a gas chromatograph (GC) equipped with a programmable
      temperature vaporizer (PTV) and a mass spectrometric (MS) detector is explored. A
      modular accelerated column heater (MACH) was used to control the temperature of
      the capillary gas chromatography column. This module can be heated and cooled
      very rapidly, shortening total analysis cycle times to a considerable extent. The
      proposed method does not require any previous analyte extraction, filtration and
      preconcentration step, as in most methods described to date. Sample preparation
      is reduced to placing the olive oil sample in the vial. This reduces the analysis
      time and the experimental errors associated with this step of the analytical
      process. By using headspace generation, the volatiles of the sample are analysed
      without interference by the non-volatile matrix, and by using injection in
      solvent-vent mode at the PTV inlet, most of the compounds that are more volatile
      than filbertone are purged and the matrix effect is minimised. Use of a liner
      packed with Tenax-TA allowed the compound of interest to be retained during the
      venting process. The limits of detection and quantification were as low as 0.27
      and 0.83 microg/L, respectively, and precision (measured as the relative standard
      deviation) was 5.7%. The method was applied to the determination of filbertone in
      spiked olive oil samples and the results revealed the good accuracy obtained with
      the method.

PMID- 19396590
TI  - Excitation and sensitization of nociceptors by bradykinin: what do we know?
AB  - Bradykinin is an endogenous nonapeptide known to induce pain and hyperalgesia to
      heat and mechanical stimulation. Correspondingly, it excites nociceptors in
      various tissues and sensitizes them to heat, whereas sensitizing effect on the
      mechanical response of nociceptors is not well established. Protein kinase C and
      TRPV1 contribute to the sensitizing mechanism of bradykinin to heat. In addition,
      TRPA1 and other ion channels appear to contribute to excitation caused by
      bradykinin. Finally, prostaglandins sensitize bradykinin-induced excitation in
      normal tissues by restoring desensitized responses due to the inhibition of
      protein kinase A.

PMID- 19396591
TI  - Measurement of instantaneous perceived self-motion using continuous pointing.
AB  - In order to optimally characterize full-body self-motion perception during
      passive translations, changes in perceived location, velocity, and acceleration
      must be quantified in real time and with high spatial resolution. Past methods
      have failed to effectively measure these critical variables. Here, we introduce
      continuous pointing as a novel method with several advantages over previous
      methods. Participants point continuously to the mentally updated location of a
      previously viewed target during passive, full-body movement. High-precision
      motion-capture data of arm angle provide a measure of a participant's perceived
      location and, in turn, perceived velocity at every moment during a motion
      trajectory. In two experiments, linear movements were presented in the absence of
      vision by passively translating participants with a robotic wheelchair or an
      anthropomorphic robotic arm (MPI Motion Simulator). The movement profiles
      included constant-velocity trajectories, two successive movement intervals
      separated by a brief pause, and reversed-motion trajectories. Results indicate a
      steady decay in perceived velocity during constant-velocity travel and an
      attenuated response to mid-trial accelerations.

PMID- 19396592
TI  - Eye-head coupling tendencies in stationary and moving subjects.
AB  - Humans exhibit considerable individuality in their propensity to make head
      movements during horizontal saccades. These variations originate in multiple
      quantifiable characteristics, including individuals' preferred ranges of gaze,
      eye-in-head, and head-on-neck eccentricity. Such "eye-head tendencies" have been
      uniformly assessed in seated subjects. It is unknown whether they continue to
      influence behavior when subjects are in motion. Previous studies of eye-head
      coordination in subjects ambulating in laboratories would predict that wholly
      different eye-head tendencies become ascendant when subjects ambulate. We tested
      this prediction by recording eye and head positions in normal subjects in an
      outdoor environment as they spontaneously regarded their surroundings while
      seated, passively riding in a wheelchair, and ambulating. Individuals exhibited
      the usual subject-to-subject variations in the preferred ranges of eye, head, and
      gaze position, but their own behavior was similar across the different
      conditions. While ambulation did affect some of the measured eye-head tendencies,
      passively riding had similar effects, indicating that these effects relate more
      to motion through the environment than to the act of walking. In a surprising
      departure from studies of eye-head coordination in subjects ambulating in
      laboratory environments, neither head nor gaze was particularly strongly aligned
      with the direction of travel. Thus, the neural mechanisms of walking do not
      demand that specific gaze or head orientations be maintained continuously, at
      least not in the common situation of a non-challenging path that can be
      negotiated without much attention. In such situations eye and head control is
      flexible, and the eye-head tendencies manifesting when stationary can emerge.

PMID- 19396593
TI  - Location-specific modulations of plantar cutaneous reflexes in human (peroneus
      longus muscle) are dependent on co-activation of ankle muscles.
AB  - Cutaneous reflexes induced in lower leg muscles by non-noxious electrical
      stimulation to the foot sole are strongly modified depending on the stimulated
      location. Little is known, however, about the functional importance of this
      location-specificity. We examined modulation of cutaneous reflexes in the
      peroneus longus muscle during co-activation of the peroneus longus (PL), soleus,
      and tibialis anterior muscles in ten healthy volunteers. We successfully recorded
      121 intramuscular single motor units (MU) of cutaneous reflexes in PL elicited by
      stimulating either fore-medial, fore-lateral, or heel regions of the plantar foot
      while performing plantarflexion and eversion (PF + EV), dorsiflexion and eversion
      (DF + EV), or isolated eversion (EV). Firing probability increased following fore
      lateral stimulation during the PF + EV and EV tasks, but not during the DF + EV.
      Fore-medial stimulation, irrespective of the task, suppressed the reflex. Heel
      stimulation facilitated the reflex only during the PF + EV and DF + EV tasks. In
      general, cutaneous reflex magnitudes were larger during the PF + EV task than
      during the others, irrespective of whether the effects were facilitatory or
      suppressive. These results suggest that the magnitude of the reflex effects on
      the PL motoneurons strongly depends on activation of plantarflexors and
      dorsiflexors.

PMID- 19396594
TI  - Intercepting moving targets: a little foresight helps a lot.
AB  - Behavioral studies suggest that humans intercept moving targets by maintaining a
      constant bearing angle (CBA). The purely feedback-driven CBA strategy has been
      contrasted with the strategy of predicting the eventual time and location of the
      future interception point. This study considers an intermediate anticipatory
      strategy of moving so as to produce a CBA a short duration into the future.
      Subjects controlled their speed of self-motion along a linear path through a
      simulated environment to intercept a moving target. When targets changed speed
      midway through the trial in Experiment 1, subjects abandoned an ineffective CBA
      strategy in favor of a strategy of anticipating the most likely change in target
      speed. In Experiment 2, targets followed paths of varying curvature. Behavior was
      inconsistent with both the CBA and the purely predictive strategy. To investigate
      the intermediate anticipatory strategy, human performance was compared with a
      model of interceptive behavior that, at each time-step t, produced the velocity
      adjustment that would minimize the change in bearing angle at time t + Deltat,
      taking into account the target's behavior during that interval. Values of Deltat
      at which the model best fit the human data for practiced subjects varied between
      0.5 and 3.5 s, suggesting that actors adopt an anticipatory strategy to keep the
      bearing angle constant a short time into the future.

PMID- 19396595
TI  - Structural basis of the anti-inflammatory activity of quercetin: inhibition of
      the 5-hydroxytryptamine type 2 receptor.
AB  - The anti-inflammatory activity of quercetin was evaluated through serotonin
      induced rat-paw edema. The experiments showed that quercetin had an important
      effect on acute inflammatory processes. Docking of serotonin and quercetin into
      the homology model of the 5-Hydroxytryptamine Type 2 Receptor allowed to analyze
      the structural basis of the anti-inflammatory activity. Results showed that
      serotonin and quercetin bind in the same region of the active site with a similar
      binding energy but quercetin has a much bigger inhibition constant. Therefore, it
      seems possible that quercetin may act as a natural inhibitor of the receptor
      blocking the acute inflammation generated by serotonin.

PMID- 19396597
TI  - Immunological evaluation of personalized peptide vaccination in combination with
      UFT and UZEL for metastatic colorectal carcinoma patients.
AB  - To investigate the safety and immunological responses of personalized peptide
      vaccination in combination with oral administration of UFT and UZEL for
      metastatic colorectal carcinoma (mCRC), fourteen patients were enrolled in the
      present study. Peptides were determined based on the presence of peptide-specific
      cytotoxic T lymphocyte precursors and IgG in each patient. A maximum of four
      peptides were subcutaneously administered weekly with UFT (300 mg/m2 day(-1)) and
      UZEL (75 mg/day) for 4 weeks, followed by 1 week of rest. This therapy was well
      tolerated although there was a grade-3 skin reaction at the vaccination site in
      one patient. An increase in peptide-specific interferon-gamma production or
      peptide-specific IgG after the tenth vaccination was observed in nine of ten or
      eight of ten patients tested, respectively. IgG responses were well correlated
      with overall survival (P = 0.0215). The safety and immunological responsiveness
      of the present therapy suggest that this combination would be of clinical benefit
      for mCRC patients, and further trials are merited.

PMID- 19396596
TI  - Bortezomib pre-treatment prolongs interferon-alpha-induced STAT1 phosphorylation
      in melanoma cells.
AB  - Bortezomib is a proteasome inhibitor that can synergize with interferon-alpha
      (IFN-alpha) to induce apoptosis in melanoma cells in vitro and inhibit tumor
      growth in vivo. We hypothesized that proteasome inhibition may be an effective
      means to sensitize melanoma cells to the direct effects of IFN-alpha. Pre
      treatment of human melanoma cells with bortezomib led to significantly increased
      transcription of interferon-stimulated genes as determined by real-time PCR. Flow
      cytometric and immunoblot analyses indicated that the enhanced direct actions of
      IFN-alpha on melanoma cells were the result of prolonged phosphorylation of STAT1
      (P-STAT1) on both the Tyrosine(701) and Serine(727) residues. In contrast, the
      enhanced IFN-alpha-induced P-STAT1 was not observed in peripheral blood
      mononuclear cells that were pre-treated with bortezomib. These data suggest that
      proteasome inhibition represents a mechanism to enhance the direct effects of IFN
      alpha on melanoma cells thereby complementing its immunostimulatory properties.

PMID- 19396598
TI  - A dose-finding and pharmacokinetic study of nedaplatin in elderly patients with
      advanced non-small cell lung cancer.
AB  - PURPOSE: Nedaplatin is a second-generation platinum showing favorable activity
      against non-small cell lung cancer (NSCLC). Dose-limiting toxicity (DLT) is
      thrombocytopenia, predicted by creatinine clearance (Ccr). This study was
      conducted to determine the recommended dose, and evaluate the toxicities,
      pharmacokinetics and efficacy for elderly NSCLC patients. METHODS: Patients > or
      =70 years were stratified into two groups based on renal functions: Group A, Ccr
      > or = 60 and Group B, 40 < or = Ccr < 60. The initial doses were 80 and 60
      mg/m(2) in Groups A and B, respectively. The doses were escalated in 20-mg/m(2)
      increments to 100 mg/m(2) until DLT. RESULTS: Chemotherapy-naive 39 elderly
      patients (Group A/Group B: 22/17) received a total of 83 cycles. Major toxicities
      were hematological. In Group A, one of the 15 patients at 100 mg/m(2) experienced
      DLT (neutropenia) and the recommended dose was determined at 100 mg/m(2). In
      Group B, three of the five patients had DLTs (leukopenia, neutropenia,
      thrombocytopenia and febrile neutropenia) at 100 mg/m(2), and the recommended
      dose was determined at 80 mg/m(2). The percentage decreases of neutrophil were
      well correlated with total and free-Pt AUCs. Partial responses were observed in
      13 (33%) of the 39 patients, and 12 of the 13 patients who responded had a
      squamous cell carcinoma. CONCLUSIONS: Nedaplatin was administered simply and
      feasibly by stratifying renal function and exerted favorable antitumor activity
      for elderly patients with NSCLC, especially on squamous cell carcinoma.

PMID- 19396599
TI  - MTT assays cannot be utilized to study the effects of STI571/Gleevec on the
      viability of solid tumor cell lines.
AB  - PURPOSE: This study will determine whether MTT assays accurately assess the
      effect of STI571 (Gleevec; Abl kinase inhibitor) on the viability of cancer cells
      containing highly active Abl kinases. METHODS: Growth kinetics, tritiated
      thymidine, fluorescent caspase, MTT, and Cell Titer Glo (CTG) assays were used to
      determine the effect of STI571 on growth, proliferation, apoptosis, and viability
      of melanoma and breast cancer cells. RESULTS: STI571 inhibited growth and
      proliferation, and increased apoptosis. However, MTT assays indicated that STI571
      increased cell viability. In contrast, STI571 induced a dose-dependent decrease
      in viability using CTG assays. CONCLUSIONS: Doses of STI571 (1-10 microM)
      required to inhibit endogenous Abl kinases interfere with the MTT assay, and
      therefore MTT cannot be used to determine the effect of STI571 on viability using
      these doses. Additionally, caution should be utilized when interpreting the
      results of MTT assays used to screen kinase inhibitors for anti-cancer activity,
      as drug effectiveness may be minimized.

PMID- 19396600
TI  - Preclinical pharmacokinetics and in vitro metabolism of brivanib (BMS-540215), a
      potent VEGFR2 inhibitor and its alanine ester prodrug brivanib alaninate.
AB  - PURPOSE: Brivanib alaninate is a prodrug of brivanib (BMS-540215), a potent oral
      VEGFR-2 inhibitor and is currently in development for the treatment of
      hepatocellular and colon carcinomas. In vitro and in vivo studies were conducted
      to characterize the preclinical pharmacokinetics and disposition of brivanib and
      brivanib alaninate, and antitumor efficacy in mice bearing human xenografts.
      METHODS: In vitro studies were conducted in liver and intestinal fractions,
      plasma and Caco-2 cells to assess the metabolic stability. Pharmacokinetics of
      brivanib were determined in preclinical species after administration of single
      intravenous or oral doses of both brivanib and brivanib alaninate. The antitumor
      efficacy was assessed at equimolar doses in nude mice bearing human tumor
      xenografts. Human efficacious dose was predicted based on projected human
      pharmacokinetic parameters and exposure at efficacious doses in the mouse
      efficacy models. RESULTS: In vitro and in vivo studies indicated that brivanib
      alaninate was efficiently converted to brivanib. Brivanib showed good brain
      penetration in rats consistent with its high intrinsic permeability and lack of
      active efflux in Caco-2 cells. The oral bioavailability of brivanib varied among
      species (22-88%) and showed dissolution rate-limited absorption even when
      combined with organic co-solvents. Administration of brivanib as brivanib
      alaninate allowed completely aqueous vehicles, and an improvement in the oral
      bioavailability (55-97%) was observed. The clearance of brivanib in humans is
      anticipated to be low to intermediate (hepatic extraction ratio < 0.7), while its
      volume of distribution is expected to be high. The minimum efficacious dose of
      brivanib alaninate was determined to be 60 mg/kg per day. CONCLUSIONS: Brivanib
      alaninate is rapidly and efficiently converted to the parent, brivanib, as
      demonstrated both in vitro and in vivo and offers an excellent mode to deliver
      brivanib orally.

PMID- 19396602
TI  - The first genome-level transcriptome of the wood-degrading fungus Phanerochaete
      chrysosporium grown on red oak.
AB  - As part of an effort to determine all the gene products involved in wood
      degradation, we have performed massively parallel pyrosequencing on an expression
      library from the white rot fungus Phanerochaete chrysosporium grown in shallow
      stationary cultures with red oak as the carbon source. Approximately 48,000 high
      quality sequence tags (246 bp average length) were generated. 53% of the sequence
      tags aligned to 4,262 P. chrysosporium gene models, and an additional 18.5% of
      the tags reliably aligned to the P. chrysosporium genome providing evidence for
      961 putative novel fragmented gene models. Due to their role in lignocellulose
      degradation, the secreted proteins were focused upon. Our results show that the
      four enzymes required for cellulose degradation: endocellulase, exocellulase
      CBHI, exocellulase CBHII, and beta-glucosidase are all produced. For
      hemicellulose degradation, not all known enzymes were produced, but
      endoxylanases, acetyl xylan esterases and mannosidases were detected. For lignin
      degradation, the role of peroxidases has been questioned; however, our results
      show that lignin peroxidase is highly expressed along with the H(2)O(2)
      generating enzyme, alcohol oxidase. The transcriptome snapshot reveals that
      H(2)O(2) generation and utilization are central in wood degradation. Our results
      also reveal new transcripts that encode extracellular proteins with no known
      function.

PMID- 19396603
TI  - Association of various inflammatory diseases with human leukocyte antigens B27,
      B7, Bw4 and Bw6 in patients with SSA.
AB  - Seronegative spondyloarthropathies (SSA) are a group of inflammatory disorders,
      which clinically involve the axial skeleton and the sacroiliiac and shoulder
      joints. The aim of the present study was to study the association of HLA B27, B7,
      Bw4 and Bw6 with some inflammatory diseases, in SSA patients in our area. A total
      of 220 SSA patients were studied and HLA typing for these antigens were done by
      the complement-mediated microcytotoxicity method. The total positivity of B27 was
      found to be 68.64% in SSA patients. Tubercular infection (chi(2) = 8.06) and
      acute anterior uveitis (chi(2) = 6.19) were found to be statistically significant
      (P < 0.05) in B27-positive SSA patients. Tuberculosis was also found to be
      significantly (chi(2) = 6.40) associated with Bw4. In SSA urinary tract
      infection, gastrointestinal infection and streptococcal infection were not
      significantly associated with B27, B7, Bw4 or Bw6 antigens. Our study concludes
      that microbial infections do have some pathogenic role in causing SSA.

PMID- 19396601
TI  - A phase I and pharmacokinetics study of intravenous calcitriol in combination
      with oral dexamethasone and gefitinib in patients with advanced solid tumors.
AB  - PURPOSE: The primary objective of this study was to determine the maximum
      tolerated dose (MTD) of intravenously (i.v.) calcitriol administered in
      combination with a fixed oral dose of dexamethasone and gefitinib in patients
      with refractory solid tumors. METHODS: A fixed oral dose of dexamethasone of 4
      mg/day was given every 12 h x 3 doses starting 12 h prior to i.v. calcitriol
      administration. Calcitriol was administered i.v. over 1 h on weeks 1, 3, and
      weekly thereafter. The starting calcitriol dose level was 57 microg and
      escalation occurred in cohorts of three patients until the MTD was defined.
      Gefitinib was given at a fixed oral daily dose of 250 mg starting at week 2 (day
      8). Serum calcitriol PK studies were performed on day 1 (calcitriol +
      dexamethasone) and on day 15 (calcitriol + dexamethasone + gefitinib). RESULTS: A
      total of 20 patients were treated. Dose-limiting hypercalcemia was observed in
      two out of the four patients receiving 163 mcg/week of calcitriol. Mean (+/-SE)
      peak serum calcitriol concentration (C (max)) at the MTD (125 microg/week
      calcitriol) was 11.17 +/- 2.62 ng/ml and the systemic exposure (AUC(0-72 h)) of
      53.30 +/- 10.49 ng h/ml. The relationship between calcitriol dose and either C
      (max) or AUC was linear over the 57-163 microg dose range. CONCLUSIONS: The
      addition of a low dose of dexamethasone allowed the safe escalation of calcitriol
      to the MTD of 125 microg/week. This dose level resulted in serum calcitriol
      concentrations that are associated with pre-clinical antitumor activity. However,
      no antitumor activity was noted clinically in patients with solid tumors.

PMID- 19396604
TI  - Survival in prostate cancer patients > or = 70 years after radical prostatectomy
      and comparison to younger patients.
AB  - PURPOSE: The purpose of our study was to evaluate and compare the survival in
      prostate cancer (PCa) patients who underwent radical prostatectomy (RP) < and >
      or = 70 years. METHODS: In a prospective cancer database, 626 patients with PCa
      underwent RP. Patients were categorised into two groups as follows: <70 years (n
      = 526, young) and > or = 70 years (n = 100, old). We evaluated the
      histopathological features as well as the clinical follow-up after RP. The median
      age was 64.4 years (41.1-80.1 years). The median follow-up was 5.3 years (0.1
      15.8 years). The preoperative median prostate-specific antigen (PSA) levels for
      young and old patients were 8.8 ng/ml (0.4-230.0 ng/ml) and 9.9 ng/ml (0.3-165.0
      ng/ml). RESULTS: Serum PSA levels were not different comparing the two groups (P
      = 0.356). The young and old patients had an organ-confined PCa in 56.3 and 58.0%
      (P = 0.826). They had well and moderately differentiated tumours in 78.7 and
      75.0% of cases and poorly differentiated tumours in 21.3 and 25.0% (P = 0.198).
      Young and old patients had an ECOG > 1 in 2.3% and 7.0% of cases (P = 0.024). A
      10-year PSA-free survival for young and old patients was 51.8 and 57.4% (P =
      0.721), 10-year-disease-specific survival was 92.3 and 97.6% (P = 0.342), 10-year
      metastasis-free survival was 86.9 and 89.7% (P = 0.713), and 10-year-overall
      survival was 78.1 and 71.2% (P = 0.565). Besides classical risk factors for
      adverse outcome on multivariate analysis, such as preoperative PSA-levels,
      extracapsular extension, tumour grade, and positive margin status, age was not a
      predictor for PSA-free- (P = 0.407), disease-specific- (P = 0.257), and overall
      survival (P = 0.121). CONCLUSIONS: In a well-selected healthy, elderly population
      survival outcome is not worse than that of younger patients with a follow-up of
      5.3 years and curative treatment should be recommended.

PMID- 19396605
TI  - Association of Escherichia coli O157:H7 with necrotizing enterocolitis in a full
      term infant.
AB  - Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of
      the neonate. NEC is predominantly seen in premature infants; however, in rare
      instances it can affect full-term infants as well. Although the pathogenesis of
      NEC remains elusive, it is well established that bacterial colonization is
      required for development of this disease. In this report, we present a case of a
      full-term infant, who developed a very aggressive form of NEC and was found to
      have Escherichia coli (E. coli) O157:H7 both in stool and blood cultures.
      Unfortunately, despite aggressive surgical and intensive care management, this
      infant suffered pan-intestinal necrosis and expired. We were not able to
      establish the route of transmission. To our knowledge, this is the first report
      of the association of E. coli O157:H7 with NEC.

PMID- 19396607
TI  - Is routine pathological examination necessary in appendectomy for acute
      appendicitis?

PMID- 19396606
TI  - Intestinal loop lengthening: early treatment of vanishing bowel.
AB  - Bianchi's procedure experience for short bowel syndrome in children is positive.
      This technique is generally performed after the first year of life. Here the
      authors propose a case of gastroschisis with prenatal spontaneous closure of
      abdominal defect and vanishing gut presenting as intestinal atresia, absence of
      ileo-cecal valve, and residual short intestinal dilatation, treated by early gut
      lengthening (ILP).

PMID- 19396608
TI  - Interleukin-6 and the serotonergic system of the medulla oblongata in the sudden
      infant death syndrome.
AB  - Mild infection may trigger sudden death in the vulnerable infant by cytokine
      interactions with a compromised medullary serotonergic (5-HT) system, leading to
      disrupted cardiorespiratory regulation and sleep-related sudden death. The
      cytokine interleukin (IL)-6 is elevated in the cerebrospinal fluid in SIDS. We
      tested the hypothesis that the expression of IL-6 receptors (IL-6R) and/or gp130
      (involved in IL-6R signaling) is altered in the medullary 5-HT system in SIDS.
      Immunohistochemistry of IL-6R and gp130 was performed on medullae from 25 SIDS
      infants, 20 infectious deaths, and 14 controls using a semi-quantitative grading
      system. In the SIDS cases, mean IL-6R intensity grade in the arcuate nucleus
      (major component of medullary 5-HT system) was significantly higher than in the
      control group (2.00 +/- 0.07 vs. 1.77 +/- 0.08, P = 0.04), with no other
      differences in IL-6R or gp130 expression at any other site. Arcuate 5-HT neurons
      expressed IL-6R, indicating a site of IL-6/5-HT interaction. In SIDS, IL-6R
      expression is abnormal in the arcuate nucleus, the putative human homolog of
      rodent ventral medullary chemosensitivity sites involving 5-HT. Aberrant
      interactions between IL-6 and the arcuate nucleus may contribute to impaired
      responses to hypercapnia generated by infection (hyper-metabolism) combined with
      rebreathing.

PMID- 19396609
TI  - Protective role of adipose-derived stem cells and their soluble factors in
      photoaging.
AB  - As individuals age, the skin undergoes changes, such as irregular pigmentation,
      thinning and loss of elasticity, that are due to both genetic and environmental
      factors. These changes may worsen, progressing to precancerous and cancerous
      diseases. Various medical treatments and topical cosmeceuticals have been used to
      treat some symptoms of photoaging, however, the results have been less than
      satisfactory. Mesenchymal stem cells within the stromal-vascular fraction of
      subcutaneous adipose tissue, adipose-derived stem cells (ADSCs), display multi
      lineage developmental plasticity and secrete various growth factors that control
      and manage the damaged neighboring cells. Recently, the production and secretion
      of growth factors has been reported as an essential function of ADSCs, and
      diverse regenerative effects of ADSCs have been demonstrated in the skin. For
      example, conditioned medium from ADSCs (ADSC-CM) stimulated both collagen
      synthesis and migration of dermal fibroblasts, which improved the wrinkling and
      accelerated wound healing in animal models. ADSC-CM also inhibited melanogenesis
      in B16 melanoma cells, and protected dermal fibroblasts from oxidative stress
      induced by chemicals and UVB irradiation. Therefore, ADSCs and soluble factors
      show promise for the treatment of photoaging, and this review introduces recent
      research developments of the ADSCs and ADSC-derived secretory factors regarding
      this issue.

PMID- 19396610
TI  - A rare cause of severe dyspareunia: a case report and literature review.
AB  - Gastrointestinal stromal tumors (GISTs) of the rectum are rare, and their
      clinical manifestations are variable. We report the case of a 23-year-old woman
      who was referred complaining of dyspareunia during coitus. We performed digital
      vaginal and rectal investigations, ultrasound, colonoscopy, and computed
      tomography. These examinations confirmed the presence of a lesion measuring about
      6 * 5 * 5 cm in size attached to the posterolateral left rectum wall. We
      performed a circumanal excision, then arrived at the mass between the muscles of
      the pelvic floor. Pathological studies indicated that the tumor was a high-grade
      GIST, and was clear at the surgical margins. On follow-up, a GIST was found at
      the gastric fundus via an endoscopic biopsy. Imatinib treatment was initiated
      because the patient refused a second operation. The gastric lesion disappeared 6
      months after imatinib treatment. Dyspareunia disappeared 1 month after operation.

PMID- 19396611
TI  - Severe factor X deficiency in a twin pregnancy.
AB  - Factor X deficiency is a rare bleeding disorder inherited in an autosomal
      recessive fashion. In severe cases with a definitive bleeding phenotype,
      prophylaxis with prothrombin complex concentrate appears to prevent bleeding very
      effectively. Management of factor X-deficient pregnant patients continues to be a
      challenge. We present a new case of successful twin pregnancy in a severe factor
      X-deficient patient.

PMID- 19396612
TI  - Patient satisfaction after lid loading in facial palsy.
AB  - Paralytic lagophthalmos is treated by pretarsal implantation of eyelid weights
      consisting either of rigid gold weights or flexible platinum chains. Functional
      results being good, subjective patient satisfaction has been examined only by a
      small number of studies. The aim of our study, conducted by means of a
      questionnaire, was to assess subjective patient satisfaction after implantation
      of different eyelid implants. Questionnaires were sent to 42 patients treated by
      pretarsal implantation of a gold weight (group 1) and 51 patients with a
      pretarsally fixed platinum chain (group 2). In total, 46 response sheets were
      evaluated (16 x gold weight, 30 x platinum chain) and the results were compared.
      In group 1, 75% of patients were very satisfied to satisfied with the overall
      result. In group 2, 100% of patients were very satisfied to satisfied with the
      overall result. In group 1, an infection occurred in 6.5% of patients, an
      extrusion in 6.5%, and a change of vision in 31%. In group 2, inflammation
      occurred in 13%, extrusion in 0%, and a change of vision occurred in 13% of
      patients. On a visual analogous scale from 1 to 10 (1, very good; 10, very poor),
      group 1 assessed the cosmetic result with an average grade of 3.8 and the
      functional result with an average grade of 3.1. Group 2 assessed the cosmetic
      result with the grade 2.9 and the functional result with grade 3.0. The
      implantation of an eyelid weight for treatment of paralytic lagophthalmos was
      assessed as positive by a majority of patients. When compared with conventional
      gold implants, patients who have been treated with a flexible platinum chain are
      overall more satisfied and have a more favorable subjective view of the cosmetic
      results.

PMID- 19396613
TI  - Sleep length and quality, sleepiness and urinary melatonin among healthy Danish
      nurses with shift work during work and leisure time.
AB  - BACKGROUND: Sleep problems are common effects of shift work. The aim of the
      present study was to evaluate how different types of shift affect sleep and
      sleepiness, and to relate sleepiness to urinary 6-sulfatoxymelatonin. METHODS: A
      total of 166 volunteer healthy Danish nurses working day, evening, or night,
      respectively fixed and mixed schedules were included. Self-reports of sleep were
      assessed together with real-time sleepiness and spot urine samples analyzed for 6
      sulfatoxymelatonin on a workday and a leisure day. RESULTS: On a day off the
      nurses slept longer, with a better quality and reported less sleepiness compared
      to a workday. Nurses on nightshift reported poorer sleep quality than nurses on
      other shifts. Sleepiness was highest for nurses on mixed schedules.
      Concentrations of urinary 6-sulfatoxymelatonin and sleepiness were generally
      correlated except for nurses working fixed nights. CONCLUSIONS: The poorest sleep
      quality was observed for nurses in mixed schedules working nights. The lack of
      correlation between sleepiness and 6-sulfatoxymelatonin on mixed night shift may
      indicate that the influence of endogenous melatonin is limited.

PMID- 19396614
TI  - Endurance and neuromuscular changes in world-class level kayakers during a
      periodized training cycle.
AB  - This study was undertaken to analyze changes in selected cardiovascular and
      neuromuscular variables in a group of elite kayakers across a 12-week periodized
      cycle of combined strength and endurance training. Eleven world-class level
      paddlers underwent a battery of tests and were assessed four times during the
      training cycle (T0, T1, T2, and T3). On each occasion subjects completed an
      incremental test to exhaustion on the kayak-ergometer to determine maximal oxygen
      uptake (VO(2max)), second ventilatory threshold (VT2), peak blood lactate,
      paddling speed at VO(2max) (PS(max)) and at VT2 (PS(VT2)), stroke rate at
      VO(2max) and at VT2, heart rate at VO(2max) and at VT2. One-repetition maximum
      (1RM) and mean velocity with 45% 1RM load (V (45%)) were assessed in the bench
      press (BP) and prone bench pull (PBP) exercises. Anthropometric measurements
      (skinfold thicknesses and muscle girths) were also obtained. Training volume and
      exercise intensity were quantified for each of three training phases (P1, P2, and
      P3). Significant improvements in VO(2max) (9.5%), VO(2) at VT2 (9.4%), PS(max)
      (6.2%), PS(VT2) (4.4%), 1RM in BP (4.2%) and PBP (5.3%), V (45%) in BP (14.4%)
      and PBP (10.0%) were observed from T0 to T3. A 12-week periodized strength and
      endurance program with special emphasis on prioritizing the sequential
      development of specific physical fitness components in each training phase (i.e.
      muscle hypertrophy and VT2 in P1, and maximal strength and aerobic power in P2)
      seems effective for improving both cardiovascular and neuromuscular markers of
      highly trained top-level athletes.

PMID- 19396615
TI  - Respiratory modulation in response to high-frequency airway occlusion delivered
      during inspiration or expiration.
AB  - To investigate whether 30 breaths performed against a high-frequency airway
      occlusion stimulus modulates ventilatory control both within-phase (within the
      phase of breathing that the stimulus was presented) and opposite-phase (in the
      opposite-phase of breathing to that in which the stimulus was presented) of the
      respiratory cycle. Ten healthy subjects (3 female, 7 male; 22-44 years old)
      completed 30 breaths prior to and following 30 inspirations or expirations
      against a high-frequency occlusion stimulus (youbreathe, Exoscience Ltd., London,
      UK), pressure-matched resistive loading or resting tidal breathing (no load)
      presented in a random order. The major findings from this study were that
      inspiratory-only high-frequency occlusion caused a significant augmentation in
      peak inspiratory airflow and shortening of expiratory time not observed during
      corresponding resistance. There were no residual effects of any intervention upon
      any measured ventilatory variables. High-frequency airway occlusion modulates
      ventilation both within-phase and in the opposite-phase, effects which are absent
      following resistive loaded breathing.

PMID- 19396616
TI  - Evoked tetanic torque and activation level explain strength differences by side.
AB  - Previous studies have demonstrated that healthy young people typically have side
      to-side differences in knee strength of about 10% when the peak torque generated
      by the stronger leg is contrasted with that of the weaker leg. However, the
      mechanisms responsible for side-to-side differences in knee strength have not
      been clearly defined. The current study tested the hypothesis that side-to-side
      knee extensor strength differences are explained by inter-limb variations in
      voluntary activation, antagonistic hamstrings activity, and electrically evoked
      torque at rest. Twenty-two volunteers served as subjects. Side-to-side
      differences in quadriceps activation and electrically evoked knee extensor torque
      explained 69% of the strength differences by side. Antagonistic hamstrings
      activity did not contribute significantly. The results suggest both central and
      peripheral mechanisms contribute to inter-limb variations in strength.

PMID- 19396617
TI  - Long-term regulation of vacuolar H(+)-ATPase by angiotensin II in proximal tubule
      cells.
AB  - Long-term effects of angiotensin II (Ang II) on vacuolar H(+)-ATPase were studied
      in a SV40-transformed cell line derived from rat proximal tubules (IRPTC). Using
      pH(i) measurements with the fluorescent dye BCECF, the hormone increased Na(+)
      independent pH recovery rate from an NH(4)Cl pulse from 0.066 +/- 0.014 pH U/min
      (n = 7) to 0.14 +/- 0.021 pH U/min (n = 13; p < 0.05) in 10 h Ang II (10(-9) M)
      treated cells. The increased activity of H(+)-ATPase did not involve changes in
      mRNA or protein abundance of the B2 subunit but increased cell surface expression
      of the V-ATPase. Inhibition of tyrosine kinase by genistein blocked Ang II
      dependent stimulation of H(+)-ATPase. Inhibition of phosphatidylinositol-3-kinase
      (PI3K) by wortmannin and of p38 mitogen-activated protein kinase (MAPK) by SB
      203580 also blocked this effect. Thus, long-term exposure of IRPTC cells to Ang
      II causes upregulation of H(+)-ATPase activity due, at least in part, to
      increased B2 cell surface expression. This regulatory pathway is dependent on
      mechanisms involving tyrosine kinase, p38 MAPK, and PI3K activation.

PMID- 19396619
TI  - Part B: Revisions to the COMFA outdoor thermal comfort model for application to
      subjects performing physical activity.
AB  - The purpose of this paper is to improve the accuracy of the COMFA outdoor thermal
      comfort model for application to subjects performing physical activity. A
      sensitivity analysis was performed to identify conditions where the COMFA model
      produced erroneous estimates of the heat and moisture exchanges between the human
      body and the ambient environment, based on data from subjects performing moderate
      to-vigorous physical activity. Errors occurred at high metabolic rates (> 400 W
      m(-2)), high wind speeds (> 4 m s(-1)) and warm air temperatures (> 28 degrees
      C). Revisions to the clothing resistance (r(c)), clothing vapour resistance (r(c
      upsilon)), skin tissue resistance (r(t)), and skin temperature (T(sk)) equations
      were proposed. The revised assessment revealed that subjects had a wide range of
      thermal acceptability (B = -20 W m(-2) to +150 W m(-2)), which was offset to the
      warm-end of the comfort scale. The revised model (COMFA*) performed well,
      predicting the actual thermal sensation of subjects in approximately 70% of
      cases. This study effectively integrated current empirical research related the
      effect of wind and activity on the clothing microclimate to improve the
      application of an outdoor thermal comfort model for subjects performing physical
      activity.

PMID- 19396620
TI  - Investigating reversals of association for utilization of recent mammography
      among Hispanic and Non-Hispanic Black women.
AB  - OBJECTIVE: Several papers have found that Hispanic and Non-Hispanic Black women
      have higher adjusted odds ratios for recent mammography when compared with Non
      Hispanic White women, even though their crude percentages were lower than, or
      about equal to, Non-Hispanic White women's. This paper investigates the existence
      of "reversals" of association for recent mammography and describes an analysis
      strategy for identifying variables that might produce them. METHODS: We used
      every-other-year data for women aged 40-80 from the 1996-2006 Behavioral Risk
      Factor Surveillance System and the 1999, 2000, 2003, and 2005 National Health
      Interview Survey. A consistent set of covariates was used across all datasets.
      RESULTS: Reversals were found in almost all survey years for Hispanic women. Non
      Hispanic Black women often had unadjusted rates comparable to Non-Hispanic
      Whites, but their adjusted odds ratios were significantly higher in most surveys.
      A limited number of variables contributed strongly to reversals, and differed
      somewhat for Hispanic and Black women. CONCLUSIONS: Reversed associations found
      in adjusted analyses present a challenge for interpretation, but could also
      denote success of programs to increase screening rates. Users of population-level
      surveys should be alert for reversals and attempt to find explanations.

PMID- 19396622
TI  - Gene expression profiles of MON810 and comparable non-GM maize varieties cultured
      in the field are more similar than are those of conventional lines.
AB  - Maize is a major food crop and genetically modified (GM) varieties represented
      24% of the global production in 2007. Authorized GM organisms have been tested
      for human and environmental safety. We previously used microarrays to compare the
      transcriptome profiles of widely used commercial MON810 versus near-isogenic
      varieties and reported differential expression of a small set of sequences in
      leaves of in vitro cultured plants of AristisBt/Aristis and PR33P67/PR33P66 (Coll
      et al. 2008). Here we further assessed the significance of these differential
      expression patterns in plants grown in a real context, i.e. in the field. Most
      sequences that were differentially expressed in plants cultured in vitro had the
      same expression values in MON810 and comparable varieties when grown in the
      field; and no sequence was found to be differentially regulated in the two
      variety pairs grown in the field. The differential expression patterns observed
      between in vitro and field culture were similar between MON810 and comparable
      varieties, with higher divergence between the two conventional varieties. This
      further indicates that MON810 and comparable non-GM varieties are equivalent
      except for the introduced character.

PMID- 19396621
TI  - Generating transgenic mice from bacterial artificial chromosomes: transgenesis
      efficiency, integration and expression outcomes.
AB  - Transgenic mice are widely used in biomedical research to study gene expression,
      developmental biology, and gene therapy models. Bacterial artificial chromosome
      (BAC) transgenes direct gene expression at physiological levels with the same
      developmental timing and expression patterns as endogenous genes in transgenic
      animal models. We generated 707 transgenic founders from 86 BAC transgenes
      purified by three different methods. Transgenesis efficiency was the same for all
      BAC DNA purification methods. Polyamine microinjection buffer was essential for
      successful integration of intact BAC transgenes. There was no correlation between
      BAC size and transgenic rate, birth rate, or transgenic efficiency. A narrow DNA
      concentration range generated the best transgenic efficiency. High DNA
      concentrations reduced birth rates while very low concentrations resulted in
      higher birth rates and lower transgenic efficiency. Founders with complete BAC
      integrations were observed in all 47 BACs for which multiple markers were tested.
      Additional founders with BAC fragment integrations were observed for 65% of these
      BACs. Expression data was available for 79 BAC transgenes and expression was
      observed in transgenic founders from 63 BACs (80%). Consistent and reproducible
      success in BAC transgenesis required the combination of careful DNA purification,
      the use of polyamine buffer, and sensitive genotyping assays.

PMID- 19396623
TI  - Intake, growth and carcass yield of indigenous goats fed market wastes of sweet
      potato (Ipomoea batatas) vines and scarlet eggplant (Solanum aethiopicum).
AB  - Intake, growth and carcass yield of indigenous goats fed basal diets of market
      wastes of sweet potato (Ipomoea batatas) vines (SPV) and scarlet eggplant
      (Solanum aethiopicum) (SEP) were examined in two experiments. In experiment I,
      the effect of presentation method (chopping, hanging or adding molasses) on the
      intake of SEP and SPV was evaluated. Presentation method did not influence the
      intake of SPV while hanging resulted in the highest (P < 0.05) intake of SEP. In
      experiment II, 24 male growing goats were supplemented with a concentrate (25%
      cottonseed cake +75% maize bran) in four dietary groups: SEPD, SPVD, SEP+SPV and
      Control where elephant grass (Pennisetum purpureum) was offered as the roughage.
      SEP were offered by hanging, while SPV were chopped. The goats were slaughtered
      after 12 weeks of feeding. Goats in the SEPD group constantly lost weight, hence
      were not followed to the end. Average daily gain and hot carcass weight were
      highest (P < 0.05) in the SPVD group (44 g/d and 8.4 kg, respectively), but
      similar between the SEP+SPV (19 and 6.8) and Control (21 and 6.9) groups. In
      conclusion, SPV can support goat meat production where standard feed resources
      are scarce when fed with an energy-protein concentrate. SEP are poorly consumed
      by goats, hence cannot be used as their sole basal feed.

PMID- 19396624
TI  - Effect of Hoodia gordonii meal supplementation at finisher stage on productivity
      and carcass characteristics of Ross 308 broiler chickens.
AB  - Two experiments were conducted to evaluate the effect of Hoodia gordonii meal
      supplementation at finisher stage on productivity and carcass characteristics of
      Ross 308 broiler chickens. The first experiment examined the effect of level of
      Hoodia gordonii meal supplementation at finisher stage (30 to 42 days of age) on
      productivity and carcass characteristics of chickens. Level of Hoodia gordonii
      meal supplementation had no effect (P > 0.05) on diet intake, growth rate, feed
      conversion ratio and live weight of chickens. Daily supplementation with 300 mg
      of Hoodia gordonii meal reduced (P < 0.05) fat pad weights by 40% in broiler
      chickens The second experiment examined the effect of Hoodia gordonii meal
      supplementation interval on the productivity and carcass characteristics of
      broiler chickens. Hoodia gordonii meal supplementation interval had no effect (P
      > 0.05) on feed intake, growth rate, live weight, feed conversion ratio and all
      carcass characteristics except fat pad of broiler chickens. Daily supplementation
      with 300 mg of Hoodia gordonii meal/bird reduced fat pad weights of the chickens
      by 18%. This could not be explained in terms of differences in feed intake,
      digestibility, or growth rate.

PMID- 19396625
TI  - A database of microsatellite genotypes for Saccharomyces cerevisiae.
AB  - A system for genotyping Saccharomyces cerevisiae is described based on a
      multiplex of ten microsatellite loci and the MAT locus. A database of genotypes
      has been developed for 246 yeast strains, including a large set of commercial
      wine yeasts, as well as 35 sequenced natural isolates currently being sequenced.
      The latter allow us, for the first time, to make direct comparisons of the
      relationship between DNA sequence data and microsatellite-based genotypes. The
      genotyping system provides a rapid and valuable system for strain identification
      as well as studying population genetics of S. cerevisiae.

PMID- 19396627
TI  - Genetic diversity in Metapenaeus dobsoni using RAPD analysis.

PMID- 19396626
TI  - Novel Hsp90 partners discovered using complementary proteomic approaches.
AB  - Hsp90 is an essential eukaryotic molecular chaperone that stabilizes a large set
      of client proteins, many of which are involved in various cellular signaling
      pathways. The current list of Hsp90 interactors comprises about 200 proteins and
      this number is growing steadily. In this paper, we report on the application of
      three complementary proteomic approaches directed towards identification of novel
      proteins that interact with Hsp90. These methods are coimmunoprecipitation, pull
      down with biotinylated geldanamycin, and immobilization of Hsp90beta on
      sepharose. In all, this study led to the identification of 42 proteins, including
      18 proteins that had not been previously characterized as Hsp90 interactors.
      These novel Hsp90 partners not only represent abundant protein species, but
      several proteins were identified at low levels, among which signaling kinase Cdk3
      and putative transcription factor tripartite motif-containing protein 29.
      Identification of tetratricopeptide-repeat-containing mitochondrial import
      receptor protein Tom34 suggests the involvement of Hsp90 in the early steps of
      translocation of mitochondrial preproteins. Taken together, our data expand the
      knowledge of the Hsp90 interactome and provide a further step in our
      understanding of the Hsp90 chaperone system.

PMID- 19396628
TI  - A novel ankyrin repeat-rich gene in potato, Star, involved in response to late
      blight.
AB  - The Solanum tuberosum ankyrin repeat gene (Star) is a novel gene from potato
      leaves challenged by Phytophthora infestans, a pathogen causing late blight
      disease. The gene was isolated, based on the reported expressed sequence tag, by
      the rapid amplification of cDNA ends. Star contains a maximum open reading frame
      of 1542 bp encoding a peptide with 514 amino acids, and it encodes a RING finger
      ankyrin repeat protein, a putative E3 ubiquitin ligase. To the authors'
      knowledge, it is the first RING finger ankyrin repeat gene isolated from the
      potato. The gene is highly expressed in roots, stems, and flowers at the
      transcript level. Star mRNA was strongly expressed from 24 to 72 h in potato
      leaves inoculated with P. infestans. The results suggested that Star may be
      involved in the development of organs and may play a role in late blight
      resistance.

PMID- 19396629
TI  - Does your health care depend on how your insurer pays providers? Variation in
      utilization and outcomes in Thailand.
AB  - Hospitals in Thailand operate in a multiple insurance payment environment. This
      paper examines (1) access to medicines and other medical technologies, (2)
      treatment outcomes, and (3) efficiency in resource use, among beneficiaries of
      the three government health insurance schemes in Thailand. Using 2003-2005
      outpatient and inpatient data for patients with three tracer diseases from three
      government hospitals, we find that utilization of more expensive items differs
      between patients whose insurers pay on a closed- or open-ended basis. Where new
      vs. conventional drugs are both available, patients whose insurer pays on a fee
      for-service basis tend to have greater access to new drugs, compared to patients
      whose insurer pays on a capitated or case basis. Similar patterns were found
      where there are options between originator versus generic drugs, drugs in
      different dosage forms, and more versus less advanced diagnostic technologies.
      Effects of insurance payment are more pronounced where price gaps among the
      medical technologies are significant. Efficiency results are mixed, depending on
      nature of the disease conditions and type of resources required for treatment.

PMID- 19396631
TI  - Utility of single luteinizing hormone determination 3 h after depot leuprolide in
      monitoring therapy of gonadotropin-dependent precocious puberty.
AB  - To determine utility of luteinizing hormone (LH) estimation, post intramuscular
      (IM) depot leuprolide in comparison with subcutaneous leuprolide stimulation
      test. Test for monitoring therapy in patients with gonadotropin dependent
      precocious puberty (GDPP). In seven patients of GDPP, who were treated with 11.25
      mg depot leuprolide, the LH peak after subcutaneous (sc) test was compared with
      LH at hourly interval for 4 h after IM depot leuprolide for 13 tests and 3rd hour
      value for next ten tests. These two values were compared both before and after
      therapy. Before therapy, the mean +/- SD LH peak after subcutaneous leuprolide
      stimulation test was 20.6 +/- 7.85 IU/l (range 9.64-30.4 IU/l), and it was 27.3
      +/- 12.21 IU/l 3 h after the first depot leuprolide injection (range 10.5-45.4
      IU/l). During therapy, the mean +/- SD of LH peak after sc stimulation test was
      1.96 +/- 0.75 IU/l (range 1.1-3.1 IU/l), and it was 2.58 +/- 0.54 IU/l (range 1.4
      3.4 IU/l) 3 h after depot leuprolide injection. Three-hour LH value following IM
      depot leuprolide injection (11.25 mg) can be used for monitoring therapy in
      patients with GDPP because of its convenience and cost effectiveness.

PMID- 19396632
TI  - Ghrelin and GHRP-6-induced ACTH and cortisol release in thyrotoxicosis.
AB  - Thyrotoxicosis might alter the hypothalamic-pituitary-adrenal (HPA) axis. We
      evaluated the effects of ghrelin and GHRP-6 on the HPA axis in 20 hyperthyroid
      patients and in 9 controls. Mean basal cortisol (microg/dl) and ACTH (pg/ml)
      levels were higher in hyperthyroidism (cortisol: 10.7 +/- 0.7; ACTH: 21.5 +/-
      2.9) compared to controls (cortisol: 8.1 +/- 0.7; ACTH: 13.5 +/- 1.8). In
      thyrotoxicosis Delta AUC cortisol values (microg/dl.90 min) after ghrelin (484 +/
      80) and GHRP-6 (115 +/- 63) were similar to controls (ghrelin: 524 +/- 107; GHRP
      6: 192 +/- 73). A significant increase in Delta AUC ACTH (pg/ml x 90 min) after
      ghrelin was observed in thyrotoxicosis (4,189 +/- 1,202) compared to controls
      (1,499 +/- 338). Delta AUC ACTH values after GHRP-6 were also higher, although
      not significantly (patients: 927 +/- 330; controls: 539 +/- 237). In summary, our
      results suggest that ghrelin-mediated pathways of ACTH release might be activated
      by thyroid hormone excess, but adrenocortical reserve is maintained.

PMID- 19396630
TI  - Systems biology and heart failure: concepts, methods, and potential research
      applications.
AB  - Dramatic advances in molecular biology dominated twentieth century biomedical
      science and delineated the function of individual genes and molecules in
      exquisite detail. However, biological processes cannot be fully understood based
      on the properties of individual genes and molecules alone, since these elements
      act in concert to enable the specific functions that make for living cells and
      organisms. The discipline of systems biology provides a novel conceptual
      framework for understanding biological phenomenon. Systems biology synthesizes
      information concerning the interactions of genes and molecules and allows
      characterization of the supramolecular networks and functional modules that
      represent the most essential aspects of cell organization and physiology.

PMID- 19396633
TI  - Developments in treatment of esophageal/gastric cancer.
AB  - Advances have been achieved in the therapy of esophageal and gastric cancer
      (including carcinoma of gastroesophageal junction); however, it poses a
      continuous challenge to treat this highly virulent disease effectively. The
      concept of the benefits of perioperative (pre- or/and post-) therapy
      (chemotherapy or chemoradiation) has been accepted and confirmed by several large
      randomized phase III studies globally in different regions, settings, and patient
      population (INT 0116, MAGIC, ACTS-GC, and JCOG 9907). Efficacy of combination of
      newer cytotoxic chemotherapy agents has been demonstrated with increased
      progression-free survival and overall survival in patients with metastatic
      disease (e.g., REAL-2, V325, SPIRITS, and COG9912). Encouraging results have been
      shown from recent preliminary data with biological and target-oriented agents in
      the treatment of esophageal and gastric cancer.

PMID- 19396634
TI  - Complications in shoulder arthroplasty: an analysis of 485 cases.
AB  - The aim of this study was to analyse the complication rates of six different
      shoulder arthroplasty concepts for different diagnoses in the short and midterm.
      The study included 485 primary shoulder arthroplasties. The mean follow-up of the
      cohort was 3.5 (1-10) years. Complications were classified into three categories:
      (1) without reoperation, (2) soft tissue revision and (3) implant revision. In
      total, 56 complications were recorded (11.6%): 34 (7%) were category 1
      complications, 11 (2.3%) were category 2 and 11 (2.3%) were category 3. For the
      whole cohort the median follow-up was 1.6 years (1-10 years) and the survival
      rate without any complication was 90.5% (95% CI: 87.9-93.1). Patients rated the
      result of their surgery in 270 (55.7%) cases as very satisfied, in 148 (30.5%) as
      satisfied, in 43 (8.9%) as somewhat disappointed and in 24 (4.9%) as
      disappointed. A relatively low complication rate was found in this study. Long
      term observations are necessary to confirm these results.

PMID- 19396635
TI  - Relationship between interferon regulatory factor 4 genetic polymorphisms,
      measures of sun sensitivity and risk for non-Hodgkin lymphoma.
AB  - OBJECTIVE: Sun exposure and sensitivity, including pigmentation, are associated
      with risk for non-Hodgkin lymphoma (NHL). One variant in the immune regulatory
      factor 4 (IRF4) gene (rs12203592) is associated with pigmentation, and a
      different IRF4 variant (rs12211228) is associated with NHL risk. We evaluated the
      independent roles of these IRF4 polymorphisms and sun sensitivity in mediating
      NHL risk and explored whether they are confounded or modified by each other.
      METHODS: Genotyping of tag single nucleotide polymorphisms (SNPs) in the IRF4
      gene was conducted in 990 NHL cases and 828 controls from a multi-center US
      study. Measures of sun sensitivity and exposure were ascertained from computer
      assisted personal interviews. We used logistic regression to compute odds ratios
      (OR) and 95% confidence intervals (CI) for NHL in relation to sun exposures, sun
      exposures in relation to IRF4 genotypes, and NHL in relation to sun exposures. We
      further assessed the effects of sun exposures in relation to IRF4 genotypes.
      RESULTS: As previously reported, we found significant associations between IRF4
      rs12211228 and NHL and between hair and eye color and NHL. The IRF4 rs12203592
      polymorphism (CT/TT genotype) was statistically significantly associated with eye
      color and particularly with hair color (OR(Light Blonde) = 0.24, 95% CI = 0.11
      0.50, overall Chi square p = 0.0002). Analysis of joint effects between eye and
      hair color with the IRF4 rs12203592 SNP did not reveal statistically significant
      p-interactions although NHL risk did decline with lighter hair color and presence
      of the variant IRF4 rs12203592 allele, compared to those without a variant allele
      and with black/brown hair color. CONCLUSIONS: Our data do not statistically
      support a joint effect between IRF4 and sun sensitivity in mediating risk for
      NHL. Further evaluation of joint effects in other and larger populations is
      warranted.

PMID- 19396636
TI  - Continuous ethanol production from cassava through simultaneous saccharification
      and fermentation by self-flocculating yeast Saccharomyces cerevisiae CHFY0321.
AB  - In this study, a fermentor consisting of four linked stirred towers that can be
      used for simultaneous saccharification and fermentation (SSF) and for the
      accumulation of cell mass was applied to the continuous production of ethanol
      using cassava as the starchy material. For the continuous process with SSF, the
      pretreated cassava liquor and saccharification enzyme at total sugar
      concentrations of 175 g/L and 195 g/L were continuously fed to the fermentor with
      dilution rates of 0.014, 0.021, 0.031, 0.042, and 0.05 h(-1). Considering the
      maximum saccharification time, the highest volumetric productivity and ethanol
      yield were observed at a dilution rate of 0.042 h(-1). At dilution rates in the
      range of 0.014 h(-1) to 0.042 h(-1), high production rates were observed, and the
      yeast in the first to fourth fermentor showed long-term stability for 2 months
      with good performance. Under the optimal culture conditions with a feed sugar
      concentration of 195 g/L and dilution rate of 0.042 h(-1), the ethanol volumetric
      productivity and ethanol yield were 3.58 g/L x h and 86.2%, respectively. The
      cell concentrations in the first to fourth stirred tower fermentors were 74.3,
      71.5, 71.2, and 70.1 g dry cell/L, respectively. The self-flocculating yeast,
      Saccharomyces cerevisiae CHFY0321, developed by our group showed excellent
      fermentation results under continuous ethanol production.

PMID- 19396641
TI  - Acute heart failure care and beyond.

PMID- 19396637
TI  - Focal nature of neurological disorders necessitates isotype-selective histone
      deacetylase (HDAC) inhibitors.
AB  - Histone deacetylase (HDAC) inhibitors represent a promising new avenue of
      therapeutic options for a range of neurological disorders. Within any particular
      neurological disorder, neuronal damage or death is not widespread; rather,
      particular brain regions are preferentially affected. Different disorders exhibit
      distinct focal pathologies. Hence, understanding the region-specific effects of
      HDAC inhibitors is essential for targeting appropriate brain areas and reducing
      toxicity in unaffected areas. The outcome of HDAC inhibition depends on several
      factors, including the diversity in the central nervous system expression of HDAC
      enzymes, selectivity of a given HDAC inhibitor for different HDAC enzymes, and
      the presence or absence of cofactors necessary for enzyme function. This review
      will summarize brain regions associated with various neurological disorders and
      factors affecting the consequences of HDAC inhibition.

PMID- 19396640
TI  - Soft tissue sarcomas with non-EWS translocations: molecular genetic features and
      pathologic and clinical correlations.
AB  - Many soft tissue sarcoma subtypes have consistent chromosomal translocations with
      novel fusion genes, which result in disordered cellular function. The microscopic
      appearances, immunophenotype and behaviour of such tumours relate to the genetic
      events to a variable extent. This paper reviews the molecular pathology and
      related morphological and clinical features of sarcomas with non-EWS
      translocations. These include synovial sarcoma, alveolar rhabdomyosarcoma,
      alveolar soft part sarcoma, dermatofibrosarcoma protuberans, low-grade
      fibromyxoid sarcoma, infantile fibrosarcoma and inflammatory myofibroblastic
      tumour.

PMID- 19396642
TI  - Society of Chest Pain Centers recommendations for the evaluation and management
      of the observation stay acute heart failure patient-parts 1-6.

PMID- 19396643
TI  - Clinical evaluation of a fully automated model-based algorithm to calculate left
      ventricular volumes and ejection fraction using multidetector computed
      tomography.
AB  - OBJECTIVES: To evaluate feasibility and accuracy of a fully automatic algorithm
      (FAA) for calculating left ventricular volumes and ejection fraction (LVEF) from
      multidetector computed tomography (MDCT) studies versus a previously validated
      method based on Simpson's method serving as our reference standard (RS), and left
      ventriculography (LVG), in patients with acute chest pain (ACP). METHODS: 23
      patients admitted with ACP underwent ECG-gated MDCT, as well as LVG during their
      hospitalization. MDCT based end-diastolic, end-systolic and stroke volumes (EDV,
      ESV, SV) and LVEF were calculated using the RS and the FAA. RESULTS: One patient
      was excluded after FAA failure to detect contours. In the remaining 22 patients,
      mean+/-SD LVEF measurements were RS 61+/-11%, FAA 59+/-11% (r = 0.91 versus RS),
      LVG 57+/-16% (r = 0.6 versus RS). In comparison to RS, FAA overestimated EDV by
      10.1+/-8.5 ml, ESV by 7.3+/-6.4 ml and SV by 3.6+/-8.6 ml, and underestimated
      LVEF measurements by 2.7+/-4.6%, related to contour smoothing. LVEF by FAA was
      within 8% of RS for all patients except one. In contrast, LVG differed
      significantly from RS. CONCLUSIONS: The evaluated FAA obtained accurate,
      clinically relevant results for left ventricular volumes and LVEF relative to the
      RS.

PMID- 19396644
TI  - Gender-specific haemodynamic and metabolic effects of a sequential training
      programme on overweight-obese hypertensives.
AB  - OBJECTIVE: To evaluate the short-term cardiometabolic effect of a sequential
      physical activity programme on pharmacologically untreated hypertensive
      overweight women and on age-matched men. METHODS: We enrolled 80 overweight
      patients with newly diagnosed hypertension, not treated with antihypertensive nor
      antihyperlipidaemic drugs or under stabilized treatment. After 3 months of AHA
      Step 2 diet, they followed a sequential training programme including 56 days of
      added 3 metabolic equivalents (METs)/week and 56 days of 6 METs/week. Dietary
      habits, anthropometric measurements, blood pressure measurement, insulin
      resistance profile and plasma lipids were monitored. RESULTS: All experienced a
      significant decrease in body mass index, waist circumference and blood pressure
      after both training, but only women experienced an improvement in diastolic blood
      pressure at the end of the intensive training phase. However, when considering
      the single pre-specified subgroups, only women experienced a significant increase
      in high-density lipoprotein cholesterol (HDL-C). Older women without metabolic
      syndrome (MS) and older men with MS experienced a decrease of HDL-C following
      moderate intensity exercise and an increase after intensive exercise. While all
      patient subgroups experienced a significant reduction in homeostasis model
      assessment (HOMA) index only after the intensive exercise phase when compared
      with the baseline, women differently experienced a significant improvement in
      HOMA index just after the moderate exercise phase and a further improvement after
      the intensive one. CONCLUSIONS: On the basis of our data, it seems that the
      metabolic and haemodynamic answer of women to physical activity is particularly
      effective and different compared with men.

PMID- 19396645
TI  - Development and validation of the sexual agreement investment scale.
AB  - Sexual agreements are ubiquitous among gay men. Lower levels of investment in
      these agreements may be associated with breaking them or engaging in risky sexual
      behavior. A scale was developed to measure agreement investment levels among gay
      men. Qualitative data from 78 gay men in committed relationships were analyzed to
      inform item development, followed by quantitative analyses of two larger samples
      (n = 380, n = 1,001) to assess construct, convergent, and discriminant validity.
      The Sexual Agreement Investment Scale (SAIS) is a psychometrically sound measure
      of the level of investment in sexual agreements among gay men in relationships.
      Men with higher agreement investment were less likely to break agreements and
      less likely to engage in unprotected anal intercourse with outside partners. The
      SAIS can be used to measure investment in sexual agreements and its impact on
      sexual behavior in a wide variety of settings, including research on
      relationships, sexuality, couples therapy and HIV prevention.

PMID- 19396646
TI  - Magazine reading and involvement and young adults' sexual health knowledge,
      efficacy, and behaviors.
AB  - These studies investigate connections between magazine reading and involvement
      and young people's sexual health knowledge, self-efficacy, intentions, and
      contraception use. Study 1 assessed sexual health behaviors and magazine reading
      among 579 undergraduate students (69% were female; 68% were White; M(age) =
      19.73). As expected, more frequent reading of mainstream magazines was associated
      with greater sexual health knowledge, safe-sex self-efficacy, and consistency of
      using contraception, although results varied across sex and magazine genre. Study
      2 replicated and expanded on these findings with a survey of 422 undergraduate
      students (51% were female; 71% were White; 49% were age 18 or younger),
      incorporating a more extensive knowledge scale, questions about safe-sex
      intentions, and measures of magazine involvement. Results suggest that magazine
      use is associated with positive sexual health outcomes among young people.

PMID- 19396647
TI  - Addressing systemic challenges in couple and family therapy research:
      Introduction to the Special Section.

PMID- 19396648
TI  - Pretreatment patient characteristics related to the level and development of
      working alliance in long-term psychotherapy.
AB  - This study explored pretreatment patient characteristics associated with the
      level and growth of working alliance in therapies lasting up to 120 therapy
      sessions. The quality of working alliance was rated by both patients (N=201) and
      therapists (N=61) at Sessions 3, 12, and 20 and then at every 20th successive
      session. Patients reported that experience with good maternal care up to
      adolescence and better current interpersonal relationships were associated with
      positive ratings of working alliance throughout therapy. Higher global
      functioning was associated with growth of alliance over time. Higher levels of
      interpersonal problems of the cold/detached kind were associated with poorer
      early working alliance. On the other hand, this type of interpersonal problems
      was also associated with improvement of working alliance over time. Therapists'
      ratings of alliance were associated with patients' intrapsychic functioning.
      Implications for treatment and research are discussed.

PMID- 19396649
TI  - Correspondence of motivational enhancement treatment integrity ratings among
      therapists, supervisors, and observers.
AB  - This study examined the correspondence of treatment integrity ratings (adherence
      and competence) among community program therapists, supervisors, and observers
      for therapists who used motivational enhancement therapy (MET) within a National
      Institute on Drug Abuse Clinical Trials Network protocol. The results suggested
      there was reasonable agreement between the three groups of raters about the
      presence or absence of several fundamental MET strategies. Moreover, relative to
      observers, therapists and supervisors were more positive in their evaluations of
      the therapists' MET adherence and competence. These findings underscore the need
      for objective monitoring of therapists' performance when using empirically
      supported treatments and for adequately training therapists and supervisors to
      evaluate their treatment implementation in community programs, and are consistent
      with observations that different perspectives on the therapeutic process are not
      interchangeable.

PMID- 19396650
TI  - The evaluation of supervision: construction of brief questionnaires for the
      supervisor and the supervisee.
AB  - This study evaluated the psychometric properties of two parallel questionnaires
      (for the supervisor and supervisee, respectively). Ninety supervisees and 37
      supervisors from different parts of Germany took part in the study. The three
      dimensions of clarifying, problem solving, and relationship were confirmed, but
      for both supervisor and supervisee versions of the scale medium intercorrelations
      also allowed a combined scale to be formed. In exploratory regression analysis,
      the relationship dimension related to both perspectives (i.e., supervisor and
      supervisee) served as the best predictor for overall supervision satisfaction.
      Despite the fact that general session satisfaction correlated in the medium range
      between supervisor and supervisee, there was no correlation between the
      perspectives as measured by the questionnaires. Possible reasons for this
      unexpected correlational pattern are discussed.

PMID- 19396651
TI  - Patient preference compared with random allocation in short-term psychodynamic
      supportive psychotherapy with indicated addition of pharmacotherapy for
      depression.
AB  - Depressed patients randomized to psychotherapy were compared with those who had
      been chosen for psychotherapy in a treatment algorithm, including addition of an
      antidepressant in case of early nonresponse. There were no differences between
      randomized and by-preference patients at baseline in adherence and outcome. About
      half of the early nonresponders refused the additional medication. However, no
      clear effect of medication addition on ultimate outcome could be demonstrated. In
      total, 37% of the patients achieved remission. The study suggested that
      randomization of patients does not induce a great influence on outcome. It might
      be warranted to continue an initially ineffective psychotherapy for depression,
      because a considerable number of patients do have a pattern of delayed response.

PMID- 19396652
TI  - Working with patients' strengths: a microprocess approach.
AB  - Previous research has supported the immediate activation of patients' strengths
      (resource activation) as an important change mechanism in psychotherapy. Two
      different studies of integrative cognitive-behavioral therapy (CBT) treatments
      demonstrated that fostered strengths-oriented CBT treatments were more effective
      than the control conditions. Within these two studies, the authors tested the
      effect of specific resource-activating strategies at the beginning of therapy
      (Sessions 2, 5, and 8) using a pairwise matched control group design. The in
      session processes were measured by video observer ratings (N=96 sessions).
      Results indicate that in the strengths-fostering treatments therapists and
      patients focus more strongly on patient competencies and personal goals in
      comparison to the control groups. These in-session processes have a direct impact
      on session outcome (particularly self-esteem, mastery, and clarification
      experiences). Results are discussed in regard to actively implementing resource
      activating behavior as superordinate principles of change and their relevance for
      therapy outcome.

PMID- 19396653
TI  - Does parent management training for children with externalizing problem behavior
      in routine care result in clinically significant changes?
AB  - The clinical significance of a parent management training that is part of the
      Prevention Program for Externalizing Problem Behavior (PEP) was assessed in an
      effectiveness trial. Parent management training was offered under routine care
      conditions in a setting where a high proportion of children were expected to show
      clinically relevant symptoms of externalizing problem behavior. At the beginning
      of the study, 32.6% to 60.7% of children were classified as clinical cases
      (dysfunctional) on three outcome measures of child behavior problems. Three
      months after treatment, 24.8% to 60.4% of children were judged to be recovered.
      Parent management training can result in clinically significant changes in
      children with externalizing behavior problems.

PMID- 19396654
TI  - Associations among attachment characteristics, patients' assessment of
      therapeutic factors, and treatment outcome following inpatient psychodynamic
      group psychotherapy.
AB  - Within a multisite study, including 289 inpatients from six different hospitals
      who underwent interpersonal-psychodynamic group psychotherapy, associations among
      attachment characteristics, therapeutic factors, and treatment outcome were
      investigated. Attachment characteristics were assessed with an interview-based
      measure (Adult Attachment Prototype Rating [AAPR]) as well as an attachment self
      report (Bielefeld Questionnaire of Client Expectations [BQCE]). Therapeutic
      factors were measured retrospectively with the Dusseldorf Therapeutic Factors
      Questionnaire and treated as an individual- as well as a hospital-specific
      characteristic. On an individual level, only the group climate factor
      independently predicted treatment outcome (i.e., Symptom Checklist-90-R Global
      Severity Index and Inventory of Interpersonal Problems mean). If simultaneously
      but separately included into a path model, analyses revealed independent
      significant effects of AAPR-Security and BQCE-Security on group climate. If
      modeled as a latent variable (common attachment security), a substantially higher
      proportion of group climate variance could be explained. Further analyses
      revealed interactions between particular therapeutic factors and attachment
      characteristics, indicating a particular importance of these therapeutic factors
      for different attachment categories.

PMID- 19396657
TI  - Potential preanalytical errors in whole-blood analysis: effect of syringe sample
      volume on blood gas, electrolyte and lactate values.
AB  - BACKGROUND: Arterial blood samples are sensitive to bias because of the
      physiological properties of blood. Several errors can occur in the preanalytical
      phase leading to incorrect diagnosis and improper treatment of patients.
      Collection of a blood specimen, as well as its handling and transport, belong to
      the key factors to affect the accuracy and good quality of clinical laboratory
      analysis. METHODS: The aim of this study was to validate the effect of different
      sample volumes on the blood gas, electrolyte and lactate values using 3 mL
      Rapidlyte plastic syringes with filter cap and Rapidlab 865 blood gas analyser.
      Also, the stability of blood gas analyser parameters with different sample volume
      was studied. RESULTS: No substantial change in blood gas, electrolyte and lactate
      parameters was found when the results of 3 mL, 1.8 mL sample volumes in the 3 mL
      syringes were compared. The sample volume of 1.0 mL or 1.5 mL in the 3 mL syringe
      is not suitable for the measurement of oxygen tension, especially when accurate
      results of pO(2) and arterial blood is needed for patient's diagnosis.
      CONCLUSIONS: The minimum sample volume when blood gases, electrolytes and lactate
      are all measured with the Rapidlab system should be 1.8 mL using 3 mL Rapidlyte
      plastic syringe with filtercap. According to this study <1.8 mL sample volumes
      can provide inaccurate results and can impose biases on measurements.

PMID- 19396658
TI  - Two weeks of overfeeding with candy, but not peanuts, increases insulin levels
      and body weight.
AB  - OBJECTIVE: To study the effects of snacking based on fast acting carbohydrates
      (candy) or fat and protein (peanuts) in a prospective randomized, parallel
      intervention study. METHODS: Basal metabolic rate (BMR) and cardiovascular risk
      factors were measured before and after hyper-alimentation by addition of 20
      kcal/kg (84 kJ/kg) body weight of either candy or roasted peanuts, to the regular
      caloric intake, for two weeks in healthy subjects. Eleven men and 14 women
      completed the randomized study. RESULTS: Energy-intake increased similarly in the
      groups (candy: +46.1+/-35%, peanuts: +46.8+/-28% p=0.96). Body-weight (candy:
      from 67.3+/-7.6 kg to 68.1+/-7.3 kg, p=0.01, nuts: from 68.7+/-6.1 kg to 69.0+/
      5.7 kg p=0.3) and waist circumference increased significantly only in the candy
      group. At the end of the study LDL cholesterol (candy: 2.6+/-0.4 mmol/l peanuts:
      2.1+/-0.4 mmol/l, p=0.005) and ApoB/ApoA-1-ratio (candy: 0.68+/-0.16 peanuts
      0.53+/-0.11, p=0.01) were higher in the candy group than in the peanut group. On
      the other hand, BMR increased only in the peanut group (candy: from 6.657+/-1.1
      MJ/24 h to 6.762+/-1.1 MJ/24 h, p=0.3 nuts: from 6.896+/-0.98 MJ/24 h to 7.256+/
      1.1 MJ/24 h, p=0.02). CONCLUSION: Two weeks of snacking based on peanuts does not
      cause the same negative metabolic effects as an isocaloric diet in which the
      snacking is based on short acting carbohydrates in the form of candy in non-obese
      healthy subjects.

PMID- 19396659
TI  - Determination of salivary cortisol by liquid chromatography-tandem mass
      spectrometry.
AB  - BACKGROUND: Late evening salivary cortisol concentrations are increasingly used
      as a screening test in suspected Cushing's syndrome partly because of easy sample
      collection. The cortisol immunoassays are prone to interference by cross-reacting
      steroids and therefore there is a need for improvement. The high specificity of
      an LC-MS assay provides a solution to the problem. METHODS: Our liquid
      chromatography-tandem mass spectrometric (LC-MS/MS) analysis utilizes only 0.1 ml
      of saliva. The samples were extracted with dichloromethane. The extract was
      evaporated to dryness and cortisol was analysed by LC-MS/MS operating in the
      negative mode ESI after separation on a reversed-phase column. RESULTS: The
      calibration curves for analysis of salivary cortisol exhibited consistent
      linearity and reproducibility in the range of 0.5-20 nmol/L. Interassay CVs were
      4.3-11% at cortisol concentrations of 0.6-14 nmol/L. The lower limit of
      quantitation (LOQ) was 70 pmol/L (signal to noise ratio=10). The mean recovery of
      the analyte added to saliva samples ranged from 95-106%. The upper limit of the
      reference range (95%) was 3.0 nmol/L. CONCLUSIONS: Our method is rapid, sensitive
      and simple to perform with a routine LC-MS/MS spectrometer.

PMID- 19396660
TI  - Serotoninergic and non-serotoninergic effects of two tricyclic antidepressants on
      visceral nociception in a rat model.
AB  - OBJECTIVE: Tricyclic antidepressants (TCAs) are well established in the treatment
      of patients with irritable bowel syndrome (IBS). The effects are believed to be
      linked to serotoninergic antinociceptive properties, but data on the
      antinociceptive effects of various TCAs with variable serotoninergic and non
      serotoninergic properties have not been investigated. The aim of this study was
      to compare the antinociceptive effects of different TCAs. MATERIAL AND METHODS:
      Colorectal distension (CRD) using a barostat device was carried out in rats and
      the visceromotor response (VMR) to CRD was quantified by abdominal wall
      electromyography. Prior to CRD, saline (control), amitriptyline (AM), desipramine
      (DES), reserpine (RES) or a combination of TCAs and RES (AM + RES or DES + RES)
      was applied intraperitoneally. Serum 5-HT levels were determined using high
      performance liquid chromatography (HPLC). RES was used to antagonize the
      serotoninergic actions of TCAs in order to discriminate between these effects and
      others. RESULTS: Both TCAs decreased the VMR compared to placebo. After RES
      application without TCAs, the VMR was increased compared to controls (6403
      microV+/-1772 microV). Co-administration of AM and RES resulted in a modest
      decrease in VMR (5774 microV+/-1953 microV), while in rats treated with RES and
      DES the VMR again was significantly lower (3446 microV (+/-1347 microV; p
      <0.05)). 5-HT levels were higher in TCA pretreated rats than those in controls
      and significantly lower 5-HT levels were found in all rats pretreated with RES.
      CONCLUSIONS: AM and DES have antinociceptive properties while RES is pro
      nociceptive. The antinociceptive effects of DES are not abolished by RES
      pretreatment, while AM only attenuates the pro-nociceptive effects of RES. The
      non-serotoninergic properties of TCAs substantially contribute to the differences
      in the antinococeptive effects of various TCAs.

PMID- 19396661
TI  - Acetaldehyde as a common denominator and cumulative carcinogen in digestive tract
      cancers.
AB  - The key issue in cancer prevention is the identification of specific aetiologic
      factors. Acetaldehyde, the first metabolite of ethanol oxidation, is carcinogenic
      in animals. ADH and ALDH2 gene mutations provide an exceptional human model to
      estimate the long-term effects of acetaldehyde exposure in man. These models
      provide strong evidence for the local carcinogenic potential of acetaldehyde also
      in humans. Ethanol is metabolized to acetaldehyde by both mucosal and microbial
      enzymes. Many microbes produce acetaldehyde from ethanol, but their capacity to
      eliminate acetaldehyde is low, which leads to the accumulation of acetaldehyde in
      saliva during an alcohol challenge. Acetaldehyde is the most abundant carcinogen
      in tobacco smoke, and it readily dissolves into saliva during smoking. Fermented
      food and many alcoholic beverages can also contain significant amounts of
      acetaldehyde. Thus acetaldehyde, derived from mucosal or microbial oxidation of
      ethanol, tobacco smoke, and/or diet, appears to act as a cumulative carcinogen in
      the upper digestive tract of humans. The evidence strongly suggests the
      importance of world-wide screening of acetaldehyde and ethanol levels in many
      beverages and foodstuffs, as well as an urgent need for regulatory measures and
      consumer guidance. Screening of the risk groups with enhanced acetaldehyde
      exposure, e.g. people with ADH and ALDH2 gene polymorphisms and hypochlorhydric
      atrophic gastritis, should also be seriously considered. Most importantly, the
      GRAS (generally regarded as safe) status of acetaldehyde, which allows it to be
      used as a food additive, should be re-evaluated, and the classification of
      acetaldehyde as a carcinogen should be upgraded.

PMID- 19396663
TI  - A benign tumour of the liver mimicking malignant liver disease--cholangiocellular
      adenoma.
AB  - OBJECTIVE: To describe three patients with liver lesions mimicking malignant
      tumours diagnosed finally, using contrast-enhanced ultrasound, as
      cholangiocellular adenoma (bile duct adenoma). MATERIAL AND METHODS: Focal liver
      lesions found incidentally in three patients. Contrast-enhanced ultrasound was
      with use of Siemens or Esaote equipment, low MI technique, after an intravenous
      bolus of 2.4 ml Sonovue (Bracco, Italy). RESULTS: Lesions were 9 mm, 15 mm and 20
      mm in diameter and all were enhanced in the arterial phase and hypo-enhanced in
      the portal venous and late phases, suggesting their malignant nature. In two
      patients, no primary liver tumour was found, and in the third patient, previously
      resected for breast cancer, a tissue specimen was considered useful for
      characterizing tumour receptors for more targeted chemotherapy, the lesion being
      assumed metastatic in nature. Transcutaneous core biopsies were performed in all
      three patients. Pathological analysis (including the reference pathology)
      revealed cholangiocellular adenoma in all of them. CONCLUSION: Cholangiocellular
      adenoma is a rare entity and can be a reason for possible false malignant
      diagnosis using contrast-enhanced ultrasound. Follow-up examinations are
      recommended.

PMID- 19396664
TI  - Food-the way to a man's heart: a mini-case series of Campylobacter
      perimyocarditis.
AB  - Campylobacter jejuni enteritis is 1 of the most common causes of food poisoning.
      Although an infrequent complication, Campylobacter associated perimyocarditis can
      have fatal consequences. This article illustrates 2 cases. We examine the types
      of Campylobacter jejuni responsible and report the observed male preponderance of
      this complication.

PMID- 19396665
TI  - One-year mortality in coagulase-negative Staphylococcus and Staphylococcus aureus
      infective endocarditis.
AB  - The aim of this study was to investigate in-hospital mortality and 12-month
      mortality in patients with coagulase-negative Staphylococcus (CoNS) compared to
      Staphylococcus aureus (S. aureus) infective endocarditis (IE). We used a
      prospective cohort study of 66 consecutive CoNS and 170 S. aureus IE patients,
      collected at 2 tertiary university hospitals in Copenhagen (Denmark) and at 1
      tertiary university hospital in Gothenburg (Sweden). Median (range) C-reactive
      protein at admission was higher in patients with S. aureus IE (150 mg/l (1-521)
      vs 94 mg/l (6-303); p<0.001), which may suggest a more serous infection. CoNS was
      associated with prosthetic valve IE (49% vs 24%; p<0.001) and median diagnostic
      delay was longer in CoNS IE patients (20 d (0-232) vs 9 d (0-132); p<0.001). In
      hospital mortality was equally high in both groups but 25% of the CoNS IE
      patients had died after 1 y compared to 39% of patients with S. aureus IE (p
      =0.05). In conclusion, CoNS IE was associated with a long diagnostic delay and
      high in-hospital mortality, whereas post-discharge prognosis was better in this
      group of patients compared to patients with IE due to S. aureus.

PMID- 19396666
TI  - Determining SARS sub-clinical infection: a longitudinal seroepidemiological study
      in recovered SARS patients and controls after an outbreak in a general hospital.
AB  - A cohort of 67 confirmed SARS patients were prospectively followed for 16 months
      and were compared with a control population. Serum samples taken at various times
      were tested for IgG and IgM; dynamic serological changes in these antibodies were
      described. The positive responses of IgM and IgG antibodies in sera against SARS
      virus from the first week to the sixth week after onset of the illness in
      patients with SARS were measured. The ELISA test of IgG antibody was negative in
      200 community controls. The positive rate in the SARS high-risk population was
      0.61% tested by ELISA and 0.21% by IFA. The high-risk population in this study
      was defined as those who provided health care and other services to SARS patients
      during the outbreak. IgG antibody in convalescent serum of patients with SARS
      revealed an increasing trend, peaking at the 22nd week after onset of illness
      followed by a slow decline. IgM appeared earlier than IgG and can be better used
      for early detection. IgG remained at a high level for a much longer period,
      serving as a good indicator for follow-up and for assessing past exposure. Our
      results also suggest that sub-clinical infection, if it exists, is very rare.

PMID- 19396667
TI  - The association between Staphylococcus aureus bacteremia and acute myocardial
      infarction.
AB  - We evaluated a possible association between S. aureus bacteremia (SAB) and the
      occurrence of myocardial infarction (MI) in 588 patients using the self
      controlled case series method. SAB increased the risk for MI 35-fold in the 2 d
      after recognition of this infection (IRR = 35.3; CI 16.7-74.7).

PMID- 19396668
TI  - Editorial. A more global arena for occupational therapy science.

PMID- 19396669
TI  - Bioethics and the explosive rise of animal law.

PMID- 19396670
TI  - Response to open peer commentaries on "Bioethical considerations in translational
      research: primate stroke".

PMID- 19396671
TI  - Bioethical considerations in translational research: primate stroke.
AB  - Controversy and activism have long been linked to the subject of primate
      research. Even in the midst of raging ethical debates surrounding fertility
      treatments, genetically modified foods and stem-cell research, there has been no
      reduction in the campaigns of activists worldwide. Playing their trade of
      intimidation aimed at ending biomedical experimentation in all animals, they have
      succeeded in creating an environment where research institutions, often painted
      as guilty until proven innocent, have avoided addressing the issue for fear of
      becoming targets. One area of intense debate is the use of primates in stroke
      research. Despite the fact that stroke kills more people each year than AIDS and
      malaria, and less than 5% of patients are candidates for current therapies, there
      is significant opposition to primate stroke research. A balanced examination of
      the ethics of primate stroke research is thus of broad interest to all areas of
      biomedical research.

PMID- 19396672
TI  - The legal regulation of primate research.

PMID- 19396673
TI  - Aping political science.

PMID- 19396674
TI  - Articulating the balance of interests between humans and other animals.

PMID- 19396675
TI  - Trade-offs in suffering and wellbeing: the utilitarian argument for primate
      stroke research.

PMID- 19396676
TI  - Nonhuman primate research: the wrong way to understand needs and necessity.

PMID- 19396677
TI  - Lost in translation: gaps in reasoning for primate stroke.

PMID- 19396678
TI  - Anosognosia, interests and equal moral consideration.

PMID- 19396679
TI  - Interests and harms in primate research.

PMID- 19396680
TI  - Primate stroke research: still not interested.

PMID- 19396681
TI  - Unintended changes in cognition, mood, and behavior arising from cell-based
      interventions for neurological conditions: ethical challenges.
AB  - The prospect of using cell-based interventions (CBIs) to treat neurological
      conditions raises several important ethical and policy questions. In this target
      article, we focus on issues related to the unique constellation of traits that
      characterize CBIs targeted at the central nervous system. In particular, there is
      at least a theoretical prospect that these cells will alter the recipients'
      cognition, mood, and behavior-brain functions that are central to our concept of
      the self. The potential for such changes, although perhaps remote, is cause for
      concern and careful ethical analysis. Both to enable better informed consent in
      the future and as an end in itself, we argue that early human trials of CBIs for
      neurological conditions must monitor subjects for changes in cognition, mood, and
      behavior; further, we recommend concrete steps for that monitoring. Such steps
      will help better characterize the potential risks and benefits of CBIs as they
      are tested and potentially used for treatment.

PMID- 19396682
TI  - Ethical challenges in cell-based interventions for neurological conditions: some
      lessons to be learnt from clinical transplantation trials in patients with
      Parkinson's disease.

PMID- 19396683
TI  - Intended changes are not always good, and unintended changes are not always bad-
      why?

PMID- 19396684
TI  - Ethical challenges to cell-based interventions for the central nervous system:
      some recommendations for clinical trials and practice.

PMID- 19396685
TI  - Inevitable challenges in establishing a causal relationship between cell-based
      interventions for neurological conditions and neuropsychological changes.

PMID- 19396686
TI  - Changes in the self: the need for conceptual research next to empirical research.

PMID- 19396687
TI  - Scare-mongering and the anticipatory ethics of experimental technologies.

PMID- 19396688
TI  - Regulating ethical issues in cell-based interventions: lessons from universal
      declaration on bioethics and human rights.

PMID- 19396689
TI  - Unintended benefits arising from cell-based interventions for neurological
      conditions.

PMID- 19396692
TI  - Immunohistochemical localization of phosphohistidine phosphatase PHPT1 in mouse
      and human tissues.
AB  - Protein histidine phosphorylation accounts for about 6% of the total protein
      phosphorylation in eukaryotic cells; still details concerning histidine
      phosphorylation and dephosphorylation are limited. A mammalian 14-kDa
      phosphohistidine phosphatase, also denominated PHPT1, was found 6 years ago that
      provided a new tool in the study of phosphohistidine phosphorylation. The
      localization of PHPT1 mRNA by Northern blot analysis revealed high expression in
      heart and skeletal muscle. The main object of the present study was to determine
      the PHPT1 expression on protein level in mouse tissues in order to get further
      information on the physiological role of the enzyme. Tissue samples from adult
      mice and 14.5-day-old mouse embryos were processed for immunostaining using a
      PHPT1-specific polyclonal antibody. The same antibody was also provided to the
      Swedish human protein atlas project (HPR)
      (http://www.proteinatlas.org/index.php). The results from both studies were
      essentially consistent with the previously reported expression of mRNA of a few
      human tissues. In addition, several other tissues, including testis, displayed a
      high protein expression. A salient result of the present investigation was the
      ubiquitous expression of the PHPT1 protein and its high expression in
      continuously dividing epithelial cells.

PMID- 19396693
TI  - Alteration of chondroitin sulfate composition on proteoglycan produced by knock
      in mouse embryonic fibroblasts whose versican lacks the A subdomain.
AB  - Versican/proteoglycan-mesenchymal (PG-M) is a large chondroitin sulfate (CS)
      proteoglycan of the extracellular matrix (ECM) that is constitutively expressed
      in adult tissues such as dermis and blood vessels. It serves as a structural
      macromolecule of the ECM, while in embryonic tissue it is transiently expressed
      at high levels and regulates cell adhesion, migration, proliferation, and
      differentiation. Knock-in mouse embryonic (Cspg2(Delta3/Delta3)) fibroblasts
      whose versican lack the A subdomain of the G1 domain exhibit low proliferation
      rates and acquire senescence. It was suspected that chondroitin sulfate on
      versican core protein would be altered when the A subdomain was disrupted, so
      fibroblasts were made from homozygous Cspg2(Delta3/Delta3) mouse embryos to
      investigate the hypothesis. Analysis of the resulting versican deposition
      demonstrated that the total versican deposited in the Cspg2(Delta3/Delta3)
      fibroblasts culture was approximately 50% of that of the wild type (WT), while
      the versican deposited in the ECM of Cspg2(Delta3/Delta3) fibroblasts culture was
      35% of that of the WT, demonstrating the lower capacity of mutant
      (Cspg2(Delta3/Delta3)) versican deposited in the ECM. The analysis of CS
      expression in the Cspg2(Delta3/Delta3) fibroblasts culture compared with wild
      type fibroblasts showed that the composition of the non-sulfate chondroitin
      sulfate isomer on the versican core protein increased in the cell layer but
      decreased in the culture medium. Interestingly, chondroitin sulfate E isomer was
      found in the culture medium. The amount of CS in the Cspg2(Delta3/Delta3) cell
      layer of fibroblasts with mutant versican was dramatically decreased, contrasted
      to the amount in the culture medium, which increased. It was concluded that the
      disruption of the A subdomain of the versican molecule leads to lowering of the
      amount of versican deposited in the ECM and the alteration of the composition and
      content of CS on the versican molecule.

PMID- 19396694
TI  - Patterns of language and auditory dysfunction in 6-year-old children with
      epilepsy.
AB  - In a previous study we reported difficulty with expressive language and
      visuoperceptual ability in preschool children with epilepsy and otherwise normal
      development. The present study analysed speech and language dysfunction for each
      individual in relation to epilepsy variables, ear preference, and intelligence in
      these children and described their auditory function. Twenty 6-year-old children
      with epilepsy (14 females, 6 males; mean age 6:5 y, range 6 y-6 y 11 mo) and 30
      reference children without epilepsy (18 females, 12 males; mean age 6:5 y, range
      6 y-6 y 11 mo) were assessed for language and auditory ability. Low scores for
      the children with epilepsy were analysed with respect to speech-language domains,
      type of epilepsy, site of epileptiform activity, intelligence, and language
      laterality. Auditory attention, perception, discrimination, and ear preference
      were measured with a dichotic listening test, and group comparisons were
      performed. Children with left-sided partial epilepsy had extensive language
      dysfunction. Most children with partial epilepsy had phonological dysfunction.
      Language dysfunction was also found in children with generalized and unclassified
      epilepsies. The children with epilepsy performed significantly worse than the
      reference children in auditory attention, perception of vowels and discrimination
      of consonants for the right ear and had more left ear advantage for vowels,
      indicating undeveloped language laterality.

PMID- 19396695
TI  - Supratrochlear foramen of the humerus: an anatomico-radiological study with
      clinical implications.
AB  - BACKGROUND: The supratrochlear foramen (STF) of the humerus has been a neglected
      entity in standard anatomy and orthopaedics text-books. The knowledge of the
      presence of STF in a humerus may be important for preoperative planning for
      treatment of supracondylar fractures. The presence of STF may also result in
      erroneous interpretation of radiographs. METHODS: The STF was studied in detail
      in 384 (220 left side and 164 right side) human dried humeri of unknown sex and
      age. The topographical anatomy of the STF was studied in detail, morphometric
      measurements were taken, and the specimens were photographed. The humerus was
      also taken for radiological assessment of the STF and supratrochlear septum.
      RESULTS: Out of the 384 bones studied, 132 cases (34.3%) showed the presence of
      STF. The STF was oval, round, and triangular in shape in 123, 7, and 2 cases,
      respectively. The mean length of the transverse diameter for supratrochlear
      foramen was 6.55 mm and 5.99 mm on the left and right sides, respectively. The
      mean length of the vertical diameter for STF was 4.85 mm and 3.81 mm on the left
      and right sides, respectively. Most of the bones that had no STF showed a
      translucency of septum, in 56.7% of the bones. CONCLUSIONS: The results of our
      study show that STF is more common on the right side, with the oval shape being
      more common. The respective sides did not exhibit any statistical significant
      differences. Presence of STF may be important for anthropological, clinical, and
      academic purpose.

PMID- 19396696
TI  - Effects of tendon transfer to restore index finger abduction for severe cubital
      tunnel syndrome.
AB  - BACKGROUND: Severe cases of cubital tunnel syndrome do not always result in
      functional recovery after surgical decompression of the ulnar nerve. A combined
      operation of tendon transfer to restore index finger abduction and decompression
      of the ulnar nerve was performed for patients with severe cubital tunnel syndrome
      who required powerful pinch strength and whose preoperative compound muscle
      action potential of the abductor digiti minimi muscle was not recordable or
      almost non-recordable. The purpose of this study was to assess the efficacy of
      tendon transfer to restore index finger abduction for severe cubital tunnel
      syndrome. METHODS: Sixteen hands in 15 patients with severe cubital tunnel
      syndrome were operated on with extensor pollicis brevis tendon transfer to the
      first dorsal interosseous muscle to restore index finger abduction and ulnar
      nerve decompression. They were reviewed after a mean follow-up of 16 months. All
      16 hands had preoperatively severe lesions with paralysis of ulnar intrinsics,
      marked anaesthesia, or hypaesthesia. RESULTS: Postoperative results were
      excellent in 2 hands, good in 10, fair in 4, and no cases with poor results
      according to Akahori's criteria. Four hands with fair results had a residual
      Froment sign or annoying hypaesthesia in the ring and little fingers. All
      patients were relieved of preoperative discomfort and showed recovery of motor
      and sensory function. The mean pre- and postoperative pinch strength was 3.3 kg
      and 5.6 kg, respectively, which showed a significant difference (P<0.01). Mean
      time of showing a negative Froment sign after surgery was 5 months in 13 cases.
      CONCLUSIONS: The extensor pollicis brevis tendon transfer is simple and useful to
      restore index finger abduction and pinch strength for severe cubital tunnel
      syndrome.

PMID- 19396697
TI  - Smoking as a product of gene-environment interaction.
AB  - A strong hereditary influence on smoking has been demonstrated. As one of the
      candidate genes in relation to smoking, the serotonin transporter gene (5-HTTLPR)
      has been suggested, however with conflicting results. In recent studies, it has
      been shown that genotypic and environmental (G*E) factors interact in the shaping
      of a variety of phenotypic expressions. The objective of the present study was to
      investigate the interaction between a variation in the 5-HTTLPR and family
      environment in relation to smoking habits, nicotine dependence, and nicotine and
      cotinine levels in hair samples. A random Swedish adolescent population sample (n
      = 785), from which 200 individuals were stratified regarding behaviour, was
      genotyped for 5-HTTLPR and assessed with semi-structured interviews, a
      questionnaire, and hair analyses of nicotine and cotinine. The 5-HTTLPR gene
      interacted with a poor family environment to predict smoking habits, as well as
      nicotine and cotinine levels. The risk of being a smoker was increased 13 times
      for an individual with a combination of the 5-HTTLPR LS genotype and a poor
      family environment in comparison with the Homozygous Long-Long (LL) genotype and
      a good family environment.

PMID- 19396698
TI  - Thrombospondin 1 expression and angiogenesis in breast carcinoma and their
      relation with platelet activity.
AB  - This study investigates angiogenesis and the expression of thrombospondin 1 in
      invasive ductal carcinoma of the breast and their possible relation to platelet
      counts and platelet activity. The study included 20 cases of invasive ductal
      carcinoma. Platelet activity was evaluated by determining thromboxane B2 and
      cyclic guanosine monophosphate (cGMP) levels by enzyme immunoassay
      (EIA).Thrombospondin (TSP) 1 and CD34 expression was studied
      immunohistochemically. Mean platelet count of the patient group was significantly
      greater than the mean platelet count of the control group (P < 0.05). The
      platelet counts were positively correlated with tumour size (r=0.609; P < 0.01).
      Platelet counts were higher in the patients who had grade 3 microvessel density
      (P < 0.05). The mean basal platelet cGMP level in the patient group was
      significantly lower than it was in the control group (P < 0.05). Focal TSP
      immunoreactivity was detectable in 5 (20%) cases in the tumour cells, and in 9
      (45%) cases in the stroma. We did not find any correlation between TSP-1 staining
      and angiogenesis, platelet counts, platelet activity, and the histological
      prognostic parameters. Our study confirms the essential role of platelets in
      tumour growth and angiogenesis. Decreased levels of cGMP in the patient group may
      cause platelet hyperreactivity. Although thrombospondin 1 may be upregulated in
      malignant breast tissue, this is not sufficient for tumour growth and
      dissemination according to our results.

PMID- 19396699
TI  - Elevated levels of thymidine kinase 1 peptide in serum from patients with breast
      cancer.
AB  - OBJECTIVES: Thymidine kinase (TK) has an important role in DNA synthesis and is
      thus related to cell proliferation and turn-over. Traditionally, TK has been
      measured by enzymatic activity or radioimmunoassays. These assays are difficult
      to adapt to random access instruments. The aim of this study was to evaluate a
      new immunological sandwich assay for detection of TK peptides in serum from
      breast cancer patients. MATERIAL AND METHODS: Serum samples were collected from
      patients with breast cancer and stored frozen at -70 degrees C. The samples were
      collected after surgery, after metastatic tumor recurrence and after chemotherapy
      due to tumour recurrence. Patients' serum samples were analysed by the TK enzyme
      linked immunosorbent assay (ELISA). RESULTS: In receiver operating
      characteristics (ROC) analyses of TK1 for diagnosis of breast cancer, the area
      under the curve (AUC) collected four weeks after surgery was 0.56 (95% CI 0.47
      0.65), for samples collected postsurgically after tumour recurrence 0.73 (95% CI
      0.65-0.80), and after chemotherapy 0.64 (95% CI 0.56-0.72). CONCLUSIONS: This
      study indicates that the tumour proliferation marker TK has a potential as a
      serum marker in breast cancer. Further studies are warranted to verify this
      observation.

PMID- 19396700
TI  - Langerhans cell histiocytosis of the sternum.
AB  - We report a rare case of Langerhans cell histiocytosis involving the sternum. The
      patient was a 12-year-old girl presenting with anterior chest pain and swelling.
      Radiographs and computed tomography showed an osteolytic lesion in the sternum.
      Technetium bone scintigraphy revealed increased uptakes in the sternum, the
      greater trochanter of the right femur, and the right distal tibia. Incisional
      biopsy for the sternum lesion was performed, and the histopathologic diagnosis
      was Langerhans cell histiocytosis. She was treated with chemotherapy and the
      symptoms disappeared.

PMID- 19396702
TI  - Panic disorder and a possible treatment approach by means of high-frequency rTMS:
      a case report.
AB  - Panic disorder still remains a pervasive, life quality impairing disorder
      requiring adequate treatment options. In this case report we present the data of
      a patient with panic disorder and comorbid depression who was treated with high
      frequency repetitive transcranial magnetic stimulation (rTMS) applied to the left
      prefrontal cortex over a course of 3 weeks. Measurements of the cerebral
      oxygenation with near-infrared spectroscopy (NIRS) during an emotional Stroop
      task before and after the rTMS treatment suggests that rTMS may modulate panic
      related prefrontal brain dysfunctions in panic patients and that it may serve as
      a possible treatment option for anxiety disorders.

PMID- 19396703
TI  - Major depression: an illness with objective physical signs.
AB  - Major depression is an illness with objective physical signs occurring with some
      consistency. These signs are retardation of movements and diminished gestures and
      expressions. The patient may appear tired, self-concerned, bored, and inattentive
      and display a loss of interest in the surroundings. Anxiety is a conspicuous and
      an integral element of affective state and may be expressed by severe
      restlessness and agitation. Muscle tension, wringing of hands, weeping and
      moaning, repeating over and over in a monotonous and stereotyped way phrases
      expressive of misery are all important clinical signs of major depression.
      Similarly tachycardia, dry tongue/mouth, sweaty palms and/or bodily extremities,
      cold clammy skin, pallor, pupillary dilatation, tremor, and the fluctuations in
      blood pressure with wide pulse pressure are all important and give away the
      underlying distress. These signs have formed an integral part of both the
      Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating
      Scale as they have a positive correlation with the diagnosis and the severity of
      illness. Current practice of operational criteria does not help exclude patients
      with subjective perception of distress and also fails to make room for
      aetiopathogenesis. The DSM-IV does not include these physical signs as an
      integral part of the clinical picture of depression, consequently leaving the
      diagnosis of MDE to subjective criteria and perceptions. This could also explain
      a large placebo response in recent randomised controlled clinical trials.

PMID- 19396704
TI  - Schizophrenia: from the brain to peripheral markers. A consensus paper of the
      WFSBP task force on biological markers.
AB  - Objective. The phenotypic complexity, together with the multifarious nature of
      the so-called "schizophrenic psychoses", limits our ability to form a simple and
      logical biologically based hypothesis for the disease group. Biological markers
      are defined as biochemical, physiological or anatomical traits that are specific
      to particular conditions. An important aim of biomarker discovery is the
      detection of disease correlates that can be used as diagnostic tools. Method. A
      selective review of the WFSBP Task Force on Biological Markers in schizophrenia
      is provided from the central nervous system to phenotypes, functional brain
      systems, chromosomal loci with potential genetic markers to the peripheral
      systems. Results. A number of biological measures have been proposed to be
      correlated with schizophrenia. At present, not a single biological trait in
      schizophrenia is available which achieves sufficient specificity, selectivity and
      is based on causal pathology and predictive validity to be recommended as
      diagnostic marker. Conclusions. With the emergence of new technologies and
      rigorous phenotypic subclassification the identification of genetic bases and
      assessment of dynamic disease related alterations will hopefully come to a new
      stage in the complex field of psychiatric research.

PMID- 19396705
TI  - The gender identity/gender dysphoria questionnaire for adolescents and adults:
      further validity evidence.
AB  - This study aimed to provide further validity evidence for the dimensional
      measurement of gender identity and gender dysphoria in both adolescents and
      adults. Adolescents and adults with gender identity disorder (GID) were compared
      to clinical control (CC) adolescents and adults on the Gender Identity/Gender
      Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA), a 27-item scale
      originally developed by Deogracias et al. (2007). In Study 1, adolescents with
      GID (n = 44) were compared to CC adolescents (n = 98); and in Study 2, adults
      with GID (n = 41) were compared to CC adults (n = 94). In both studies, clients
      with GID self-reported significantly more gender dysphoria than did the CCs, with
      excellent sensitivity and specificity rates. In both studies, degree of self
      reported gender dysphoria was significantly correlated with recall of cross
      gender behavior in childhood-a test of convergent validity. The research and
      clinical utility of the GIDYQ-AA is discussed, including directions for further
      research in distinct clinical populations.

PMID- 19396706
TI  - Introduction: harmony in chaos: social work responses to issues arising from a
      changing and stressful world, part 2.

PMID- 19396707
TI  - Supervisory communication, burnout, and turnover intention among social workers
      in health care settings.
AB  - The current study tests the effects of different types of supervisory
      communication on burnout and turnover intention among health social workers. The
      study proposed a conceptual model of supervisory communication and tested it
      empirically using structural equation modeling (SEM) techniques with a random
      sample of 211 California state-registered social workers working in health or
      mental health care settings. The results of the present study provide empirical
      evidence of the unique roles that different types of supervisory communication
      play as antecedents of burnout and turnover intention. Specifically, supportive
      relationship communication had an indirect effect on burnout and turnover
      intention through its effect on perceived stress, whereas job-relevant
      communication had not only an indirect effect on burnout and turnover intention
      through its effect on stress, but also a direct effect on turnover intention. In
      addition, the results showed that upward communication moderated the relationship
      between stress and burnout. Implications for social work administration and
      possible elaboration of the theoretical framework are discussed.

PMID- 19396708
TI  - Factors affecting life-sustaining treatment decisions by health care surrogates
      and proxies: assessing benefits and barriers.
AB  - Terri Schiavo's life and death placed international focus on social workers' need
      to better understand and serve health care surrogates and proxies making life
      sustaining treatment decisions on behalf of medical patients. This study (N =
      132) reports initial validation of a new measure, the Acceptance of Treatment
      Choice Inventory (ATCI), designed to evaluate benefits and barriers considered by
      health care surrogates and proxies prior to making a life-sustaining treatment
      decision about CPR, tube-feedings, dialysis, and ventilation. Affirming a two
      factor model with acceptable reliability and preliminary construct validity,
      surrogates sought decision support and desired to represent patients' wishes
      adequately.

PMID- 19396709
TI  - Against all odds: resilience in single mothers of children with disabilities.
AB  - There is a substantial body of literature that explores family adaptation within
      the context of childhood disability. However, closer analysis indicates that the
      primary focus of this research is concentrated on two-parent family systems.
      Despite evidence to suggest that single mothers are more likely to be parenting
      children with disabilities, their experiences have received minimal attention
      within social science research. Furthermore, when single mothers do become the
      focus of study, much of the attention is directed toward identifying the deficits
      within their family systems. Grounded in an integrated family resilience
      framework, the intent of this study was to explore the family adaptation of
      single mothers of children with disabilities within a longitudinal framework and
      to identify the individual, family, social, and environmental factors that
      contribute toward resilience within this population. Study participants consisted
      of 15 single mothers who had previously participated in the "Family Strengths and
      Childhood Disability" research project. Mothers were interviewed with the view
      toward identifying their perceptions of what constitutes risk and protective
      factors, and exploring these in the context of family adaptation and resilience.
      Findings revealed a marked contrast between public discourses about single
      motherhood and childhood disability and the personal narratives of the mothers in
      this study. Concepts of family resilience were revealed by mothers who challenged
      definitions of single mothers as inadequate, who disputed the definition of their
      children as "disabled," and who moved from a position of received to
      authoritative knowledge. The study demonstrates that in contrast to public
      perceptions, single mothers of children with disabilities view their experiences
      as personally transformative and as a means of building confidence that empowers
      them to further disrupt negative expectations of their families.

PMID- 19396710
TI  - Repeat substance-using suicidal clients-how can we be helpful?
AB  - Care of clients with mental health and substance abuse problems accounts for a
      significant proportion of all emergency department (ED) visits. This qualitative
      research project sought to understand the ED experiences of men with a history of
      suicidal behavior and substance abuse and those of the emergency personnel who
      work with them. Understanding the unique positions of care providers and this
      client population in the ED setting can assist the social worker to advocate for
      this highly vulnerable group of clients and to assist an interprofessional team
      to develop better crisis interventions.

PMID- 19396711
TI  - From burden to depressive symptoms: the case of Chinese-Canadian family
      caregivers for the elderly.
AB  - This study aims to understand the effect of caregiving burden on depressive
      symptoms in Chinese-Canadian family caregivers, an area on which little research
      has been conducted. A random sample of 339 Chinese-Canadian caregivers for
      elderly family members completed a structured telephone survey. The results
      showed that depressive symptoms were predicted positively by caregiving burden,
      while caregiving burden was predicted negatively by financial adequacy and
      positively by the level of activities of daily living (ADL) and instrumental
      activities of daily living (IADL) caregiving assistance provided. Culturally
      appropriate strategies are needed to support Chinese family caregivers in order
      to properly manage caregiving responsibilities, financial needs, and
      psychological burden.

PMID- 19396712
TI  - An evaluation of pediatric asthma educational resources.
AB  - The purpose of this study was to evaluate newly developed educational resources
      for children with asthma. Children with asthma, their parents, and pediatric
      health care professionals were invited to review age-appropriate asthma
      resources. Key findings revealed: (1) the perceived usefulness of these
      resources, particularly for creating discussion opportunities between children
      and their caregivers through implemented resource use; (2) the need for health
      education materials to balance goals of depth of information versus child
      enjoyment in order to increase effective knowledge transfer and application; and
      (3) a renewed call for future educational resources to be both relevant and
      interactive in their outreach and engagement of children, potentially involving
      mediums of advanced technology. Clinical experience and the literature note a
      current lack of pediatric asthma education materials. The positive findings of
      this review of novel educational materials in asthma address an important gap
      relative to pediatric practice, resource evaluation, and knowledge translation.

PMID- 19396713
TI  - Zen practice: a training method to enhance the skills of clinical social workers.
AB  - The use of Zen Buddhist meditation in clinical practice has received specific
      attention from mental health disciplines in the West. A study was undertaken to
      examine the influence of a personal practice of Zen on the professional work of
      clinical social workers. Ten experienced clinical social workers who were long
      term Zen practitioners were interviewed. Findings from this qualitative study
      suggest that Zen meditation has direct application to clinical social work in
      three areas: (1) cultivating Awareness, (2) enhancing Acceptance, and (3)
      nurturing Responsibility. This article reports on the findings in the area of
      Awareness. Awareness increases a social worker's focus on the present moment with
      the client, providing for a suspension of preconceived ideas about the client.
      Building on the view that social work is both art and science, the author
      proposes the use of Zen in the training of clinical social workers.

PMID- 19396714
TI  - Private prayer and quality of life in cardiac patients: pathways of cognitive
      coping and social support.
AB  - Despite the growing evidence linking faith with health and well-being, national
      leaders noted the need to explore the mechanism underlying these linkages. The
      goal of this prospective study was to investigate the psychosocial mechanisms
      involved in the preoperative use of private prayer for coping and the effects of
      such act on short-term quality of life (SPQOL) in 294 patients following open
      heart surgery. Using established instruments, three interviews were conducted
      with middle-aged and older patients (average age 62) at two weeks and two days
      preoperatively, then 36 days postoperatively. The endpoints were assessed with
      levels of distress (e.g., depression and anxiety) and fatigue symptoms.
      Structural equation modeling was used to test a theoretical model. The final
      model showed the indirect influence of using prayer for coping on SPQOL through
      the mediation of cognitive coping and perceived social support. However, this
      mediation was not observed for behavioral, anger, and avoidant coping.
      Psychosocial factors may explain the potential role of using prayer for coping on
      short-term postoperative quality of life.

PMID- 19396715
TI  - The meaning of oral health-related quality of life for elderly persons with
      dementia.
AB  - OBJECTIVE: Studies of oral health developments increasingly include self-reported
      assessments of how oral health affects quality of life (QoL), referred to as
      "oral health-related QoL". People with dementia are often excluded in studies of
      oral health-related QoL and thus our aim in this study was to explore this area
      in elderly persons with dementia. MATERIAL AND METHODS: Eighteen elderly
      individuals (aged between 78 and 94 years) with dementia of varying degrees of
      severity were interviewed with the aid of an interview guide; pictures and
      objects were used as stimulus material (triggers). The material was analyzed
      using grounded theory as point of departure, and a professional assessment of the
      oral health of the participants was used as reference. RESULT: Four categories
      were identified: the ability to chew and eat, independence, oral problems, and
      teeth are important. These factors are largely consistent with those that have
      emerged in earlier studies of the elderly, but in some cases less pronounced in
      persons with dementia. CONCLUSION: The use of triggers is a positive way to
      communicate oral health-related QoL among persons suffering from dementia,
      although the material used in this study needs further evaluation and
      development.

PMID- 19396716
TI  - A comparison of three methods of using transtympanic electrocochleography for the
      diagnosis of Meniere's disease: click summating potential measurements, tone
      burst summating potential amplitude measurements, and biasing of the summating
      potential using a low frequency tone.
AB  - CONCLUSION: Stimulus biasing modulated the amplitude of the tone burst evoked
      summating potential (SP) in ears affected by Meniere's disease less than in
      normal ears. A reduced SP bias ratio added diagnostic accuracy for the diagnosis
      of Meniere's disease. OBJECTIVES: To evaluate the effect of stimulus biasing on
      the human tone burst SP, and to determine if stimulus biasing could contribute to
      the electrocochleography as a means of confirming the diagnosis of Meniere's
      disease. PATIENTS AND METHODS: Patients referred for transtympanic
      electrocochleography (TT ECochG) were assessed prospectively on clinical grounds
      according to the AAO-HNS criteria and a scale devised by one of the authors. A
      Meniere's group of ears and a non-Meniere's group of ears was determined. The
      ears opposite a Meniere's ear were not included in the analysis. The ratio of the
      click SP amplitude and the action potential (AP) amplitude (SP/AP ratio), the
      tone burst SP amplitude at 500 Hz,1 kHz, 2 kHz and 8 kHz, and the effect of
      stimulus biasing on the tone burst SP were measured. RESULTS: A unipolar stimulus
      biasing ratio established for the modulation of the 1 kHz tone burst SP separated
      the Meniere's ears from the non-Meniere's ears with a sensitivity of 85% at a
      specificity of 80.6% and the difference between groups reached statistical
      significance (p=0.016). The 1 kHz SP amplitude measurements and the stimulus
      biasing measurements were superior to the click SP/AP ratio for identifying the
      Meniere's group. A combination of 1 kHz SP amplitude measurements and SP bias
      ratio separated the Meniere's ears from the non-Meniere's ears with an accuracy
      of 85%.

PMID- 19396717
TI  - Hair removal with a novel, low fluence, home-use intense pulsed light device.
AB  - OBJECTIVE: To evaluate the reduction in unwanted body and facial hair at various
      body sites of Fitzpatrick skin types I-III and the efficacy, comfort and safety
      of this treatment intended for home-use by the general public. METHODS: In this
      non-randomized study, 29 individuals were given three sequential weekly
      treatments on a total of 31 body and facial areas including the axilla, bikini
      area, abdomen, neck, chin and upper lip using a novel intense pulsed light
      device. All participants completed a simple self-assessment questionnaire, as
      well as an evaluation of pain/discomfort. RESULTS: The mean reduction in terminal
      hair counts was 47% at 4 weeks' follow-up and 41% at 6 months' follow-up after
      completing three sequential weekly treatments. Overall, 84% of participants
      showed a significant percentage of hair reduction (p<0.01) at the 6-month follow
      up, with a mean of 51% (range 25-86%). No treatment-related side effects were
      reported, with little or no discomfort reported during the treatment. Only mild
      erythema was noted immediately post-treatment. In total, 85% of the participants
      were either pleased or very pleased with the results 1 month after the third
      treatment. CONCLUSIONS: In simulated consumer use, this home-use IPL demonstrated
      a significant, quantifiable and sustainable reduction in unwanted body and facial
      hair with minimal side effects.

PMID- 19396718
TI  - Expression of the water channel protein, aquaporin-4, in mouse brains exposed to
      mobile telephone radiofrequency fields.
AB  - AIM: To determine whether exposure to mobile telephone radiofrequency (RF)
      fields, either acutely or long-term, produces up-regulation of the water channel
      protein, aquaporin-4 (AQP-4). METHODS: Using a purpose-designed exposure system
      at 900 MHz, mice were given a single, far-field whole body exposure at a specific
      absorption rate of 4 W/kg for 60 minutes or a similar exposure on 5 successive
      days/week for 104 weeks. Control mice were sham-exposed or freely mobile in a
      cage to control for any stress caused by restraint in the exposure module. A
      positive control group was given a clostridial toxin known to cause microvascular
      endothelial injury, severe vasogenic oedema and upregulation of AQP-4. Brains
      were perfusion fixed with 4% paraformaldehyde, coronal sections cut from six
      levels, and immunostained for the principal water channel protein in brain, AQP
      4. RESULTS: There was no increase in AQP-4 expression in brains exposed to mobile
      phone microwaves compared to control (sham exposed and freely moving caged mice)
      brains after short or protracted exposure, while AQP-4 was substantially
      upregulated in the brains of mice given the clostridial toxin. CONCLUSION: Brains
      exposed to mobile telephone RF fields for a short (60 minutes) or long (2 years)
      duration did not show any immunohistochemically detectable up-regulation of the
      water channel protein, AQP-4, suggesting that there was no significant increase
      in blood-brain barrier permeability

PMID- 19396719
TI  - Acquired lymphangiectasia ('lymphangioma circumscriptum') of the vulva: a report
      of eight cases.
AB  - AIMS: To present the clinico-pathological findings of eight cases of acquired
      vulval lymphangiectasia (AVL) with discussion of the terminology and differential
      diagnosis. METHODS: Vulvectomy or biopsy specimens from eight patients with AVL
      were reviewed. All patients had undergone surgery, lymphadenectomy and/or
      radiotherapy, most commonly for carcinoma of the cervix, up to 26 years prior to
      presentation with the lymphangiectatic lesions. Immunohistochemistry for CD31,
      CD34, D2-40, p53 and p16 was performed in each case. RESULTS: The original
      clinical and pathological diagnoses were most frequently 'lymphangioma
      circumscriptum' but viral infection was considered in some cases. All specimens
      showed dermal lymphangiectasia associated with marked reactive epidermal
      hyperplasia. The lymphatic endothelial cells showed CD31 and D2-40 expression but
      CD34 was negative. The keratinocytes showed focal p53 immunoreactivity in four
      cases. CONCLUSIONS: AVL is the preferred nomenclature for the lesions presented
      herein. The clinical and histological features usually are characteristic but the
      differential diagnosis may include condyloma and differentiated type vulval
      intraepithelial neoplasia (VIN). Immunohistochemistry may be helpful but lack of
      CD34 expression should be noted and may prove useful in the differential
      diagnosis of other vulval vascular lesions. Focal p53 protein immunoreactivity
      should not be considered indicative of differentiated type VIN in this clinical
      setting.

PMID- 19396720
TI  - Comparative proteomic studies of plasma from children with pneumococcal
      pneumonia.
AB  - Streptococcus pneumoniae is the primary pathogen causing community acquired
      pneumonia in children. Despite medical progress, the prevalence of complicated
      pneumococcal pneumonia became increased without apparent explanations. Two
      dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were used to
      compare the plasma protein profiles from children with different severities of
      pneumococcal pneumonia. Plasma samples from 14 cases, 7 with complicated and the
      other 7 with uncomplicated pneumonia, were analyzed. Complicated pneumonia was
      defined by the presence of pleural fluid parameters consistent with empyema,
      and/or a computed tomography compatible with necrotizing pneumonitis. The normal
      control group included 7 age-matched volunteers. By comparing the plasma proteins
      of patients with different severities, 4 proteins with significant differences
      were identified. The up-regulated proteins were haptoglobin and immunoglobulin
      kappa chain. The down-regulated were apolipoprotein A-I (Apo-AI) and
      transthyretin. All these proteins are known to take part in the inflammation
      reaction, which implicates the active innate immune responses in severe
      infections of S. pneumoniae. In addition, the up-regulated haptoglobin, which
      protects lung tissues against oxidative damage by the clearance of hemoglobin,
      can also act as an inflammatory inhibitor. Thus, our data seem to indicate that
      inflammation balance may take place in the occurrence of complicated pneumococcal
      pneumonia.

PMID- 19396722
TI  - Measurement of pelvic floor function during physical activity: a feasibility
      study.
AB  - OBJECTIVE: Pelvic floor function is closely related to bladder storage or voiding
      dysfunctions. So far, however, pelvic floor activity has not been reliably
      measured during physical activity. MATERIAL AND METHODS: In 14 female healthy
      volunteers, the activity of the pelvic floor was evaluated during a standardized
      horseback riding course by a biofeedback device. RESULTS: Pelvic floor activity
      could be reliably measured during horseback riding. Each pace was associated with
      corresponding electromyographic (EMG) activity that was similar in the
      overwhelming majority of participants. Different paces demonstrated distinctly
      different EMG activities. CONCLUSIONS: To the authors' knowledge, this study is
      the first to demonstrate that pelvic floor activity can be reliably measured
      during physical activity with a commercially available biofeedback device.

PMID- 19396721
TI  - Multiresistant CTX-M-15 ESBL-producing Escherichia coli in southern Sweden:
      Description of an outbreak.
AB  - An outbreak caused by a multiresistant Escherichia coli producing CTX-M-15 ESBL
      occurred during autumn 2005 and spring 2006 in Kristianstad, a town in southern
      Sweden. The outbreak comprised 27 cases and was related to an infectious diseases
      ward and a neighbouring long-term care facility. Our primary objective was to
      investigate the epidemiology in order to control the outbreak. In addition, we
      studied the time of carriage of multiresistant ESBL-producing Escherichia coli by
      follow-up samples and measured the frequency of carriage of ESBL-producing
      bacteria in the patient population admitted to the infectious diseases ward
      during autumn 2006. The outbreak described is one of the first caused by ESBL
      producing Escherichia coli in Sweden. The source of the outbreak was not found.
      Infection control measures were reinforced in the outbreak situation, and
      epidemiological and microbiological methods, including PFGE typing, were used for
      analysis. The carriage time of multiresistant Escherichia coli was longer in
      several of the affected patients than has previously been reported. The longest
      carriage time to date is 33 months. This demonstrates the risk for new outbreaks
      unless strict infection control measures are implemented. Among the patients
      admitted to the ward during autumn 2006, 2.5% carried ESBL-producing
      enterobacteria.

PMID- 19396724
TI  - Granulomatous epididymo-orchitis, a rare complication of intravesical bacillus
      Calmette-Guerin therapy for urothelial cancer.
AB  - Only a few cases of tuberculous epididymo-orchitis after bacillus Calmette-Guerin
      (BCG) therapy have been published. This report presents a case of granulomatous
      epididymo-orchitis after intravesical BCG therapy in a patient presenting with
      pain and unilateral swelling of the scrotal content. This complication should
      always be considered when a patient presents with these symptoms after BCG
      therapy. Isoniazid may be used as a first choice of treatment.

PMID- 19396723
TI  - Naftopidil and propiverine hydrochloride for treatment of male lower urinary
      tract symptoms suggestive of benign prostatic hyperplasia and concomitant
      overactive bladder: a prospective randomized controlled study.
AB  - OBJECTIVE: To assess the efficacy and safety of propiverine hydrochloride
      (antimuscarinic), naftopidil (alpha(1)-adrenoceptor antagonist) or both in
      patients with male lower urinary tract symptoms (LUTS) suggestive of benign
      prostatic hyperplasia and concomitant overactive bladder (OAB). MATERIAL AND
      METHODS: Men aged at least 50 years who had a total International Prostate
      Symptom Score (IPSS) of 8 or higher and bladder dairy documenting micturition
      frequency (more than eight micturitions/24 h) and urgency (more than one
      episode/24 h), with or without urgency urinary incontinence were randomized into
      three groups: group N, naftopidil (50 mg once daily) only; group P, propiverine
      hydrochloride (20 mg once daily); and group NP, naftopidil (50 mg once daily)
      plus propiverine hydrochloride (20 mg once daily) for a 4-week treatment regimen.
      RESULTS: A total of 66 men, including 20 in group N, 23 in group P and 23 in
      group NP, were treated and 58 (87.9%) completed the 4 weeks of treatment. IPSS
      improved significantly in groups N and NP. Urinary frequency improved
      significantly in groups P and NP. Postvoid residual urine volume increased
      significantly in groups P and NP. Significant improvements in urgency episodes
      were noted in each group. One patient in group P required catheterization owing
      to acute urinary retention and another stopped medication because of difficulty
      in voiding. CONCLUSION: These results suggest that each treatment showed
      effectiveness for male LUTS with OAB. However, there are some possibilities of
      adverse effects with propiverine hydrochloride monotherapy.

PMID- 19396726
TI  - Circadian rhythm of neutrophil counts and granulocyte macrophage-colony
      stimulating factor (GM-CSF) under clozapine treatment: a case report.
AB  - Agranulocytosis is a severe side effect of clozapine which requires stopping this
      medication immediately in the case of progressive neutropenia. There are,
      however, cases of benign neutropenia under clozapine that do not progress. The
      ability to predict progression vs. non-progression in neutropenia cases under
      clozapine would be highly valuable for avoiding unnecessary treatment
      withdrawals. In this context, we closely monitored circadian neutrophil counts
      and granulocyte macrophage-colony stimulating factor (GM-CSF) levels in a patient
      who had low normal neutrophil counts at baseline and developed neutropenia under
      clozapine treatment. METHODS: Venous blood samples were drawn in close intervals
      for 4 weeks. At several time points blood was sampled in the morning between
      08:30 and 9:30 h and a second time in the afternoon between 14:00 and 15:00 h.
      RESULTS: The circadian rhythm of neutrophil counts and GM-CSF levels was
      unchanged. There was no progression to agranulocytosis, and clozapine could be
      continued. CONCLUSIONS: In view of the available literature and the presented
      case it is suggested that further studying of circadian profiles of neutrophil
      counts, neutrophil regulatory factors, such as GM-CSF, and their intercorrelation
      may help to find a biomarker of benign vs. malign neutropenia under clozapine.

PMID- 19396727
TI  - Can the role of genetic factors in schizophrenia be enlightened by studies of
      candidate gene mutant mice behaviour?
AB  - Schizophrenia is one of the most severe psychiatric disorders. Despite the
      knowledge accumulated over years, aetiology and pathophysiology remain uncertain.
      Research on families and twins suggests that genetic factors are largely
      responsible for the disease and implies specific genes as risk factors. Genetic
      epidemiology indicates a complex transmission mode, compatible with a multi-locus
      model, with single genes accounting for specific traits rather than for the
      entire phenotype. To better understand every single gene contribution to
      schizophrenia, the use of intermediate endophenotypes has been proposed. A
      straight communication between preclinical and clinical researchers could
      facilitate research on the association between genes and endophenotypes. Many
      behavioural tasks are available for humans and animals to measure endophenotypes.
      Here, firstly, we reviewed the most promising mouse behavioural tests modelling
      human behavioural tasks altered in schizophrenia. Secondly, we systematically
      reviewed animal models availability for a selection of candidate genes, derived
      from linkage and association studies. Thirdly, we systematically reviewed the
      studies which tested mutant mice in the above behavioural tasks. Results indicate
      a large mutant mice availability for schizophrenia candidate genes but they have
      been insufficiently tested in behavioural tasks. On the other hand, multivariate
      and translational approach should be implemented in several behavioural domains.

PMID- 19396728
TI  - Effect of dopamine on intracellular sodium: a common pathway for pharmacological
      mechanism of action in bipolar illness.
AB  - BACKGROUND: The pathogenesis of bipolar illness is unknown. A search for common
      mechanism of action in effective medications has been utilized as a method to
      gain clues into mechanisms of illness. The recent increase of reports of
      documented efficacy of first- and second-generation antipsychotics in the control
      of mania offers a new opportunity to gain insight into the pathophysiological
      mechanism of bipolar disorder. METHODS: A selected critical review of the
      literature is performed to gain insights into the effect of antipsychotic
      medications on ion regulation. RESULTS: Dopamine D(1) and D(2) receptor
      stimulation increases intracellular sodium concentrations. D(1) and D(2) blockade
      normalizes stimulated intracellular sodium concentrations, and increases active
      sodium pump expression. CONCLUSIONS: A similar exercise has previously suggested
      that lithium and effective anticonvulsants reduce sodium influx in an activity
      dependent manner. The current review suggests that antipsychotic medications may
      have a similar effect by a different mechanism. The role of ion dysregulation in
      the genesis of mania in bipolar illness needs to continue to be examined.

PMID- 19396729
TI  - Quantifying nonlinear anisotropic elastic material properties of biological
      tissue by use of membrane inflation.
AB  - Determination of material parameters for soft tissue frequently involves
      regression of material parameters for nonlinear, anisotropic constitutive models
      against experimental data from heterogeneous tests. Here, parameter estimation
      based on membrane inflation is considered. A four parameter nonlinear,
      anisotropic hyperelastic strain energy function was used to model the material,
      in which the parameters are cast in terms of key response features. The
      experiment was simulated using finite element (FE) analysis in order to predict
      the experimental measurements of pressure versus profile strain. Material
      parameter regression was automated using inverse FE analysis; parameter values
      were updated by use of both local and global techniques, and the ability of these
      techniques to efficiently converge to a best case was examined. This approach
      provides a framework in which additional experimental data, including surface
      strain measurements or local structural information, may be incorporated in order
      to quantify heterogeneous nonlinear material properties.

PMID- 19396731
TI  - The influence of gender roles on health seeking behaviour during pregnancy in
      Turkey.
AB  - OBJECTIVES: To explore the impact of gender roles in relation to health seeking
      behaviour during pregnancy and childbirth. METHODS: The study was conducted in
      neighbourhoods with low antenatal care rates in three provinces of Turkey. The
      study population consisted of pregnant women who never got or discontinued
      antenatal care and their peers, families and community leaders. Sixteen focus
      group discussions and 125 in-depth interviews were conducted with a total of 239
      participants. RESULTS: Pregnancy and childbirth are interwoven strongly with
      gender roles. Since the patriarchal system acknowledges women through the means
      of childbirth, women are expected to have many children. Hence women experience
      pregnancy as a burden and are not motivated to seek antenatal care. During
      pregnancy, only 'serious' conditions are considered as legitimate reasons for
      accessing care. However, the decision regarding whether a pregnant woman is
      seriously sick or not belongs to the responsibilities of elder women, which
      delays service use. CONCLUSIONS: Providing information regarding the value of
      antenatal care also to elder women is essential in increasing the demand to the
      services. Incorporating gender perspectives into daily health practice and
      maintaining access to high quality reproductive care services are vital in
      reducing the gender based barriers to care.

PMID- 19396732
TI  - Sentence comprehension affects the dynamics of bimanual coordination:
      implications for embodied cognition.
AB  - Recent work in embodied cognition has demonstrated that language comprehension
      involves the motor system (e.g., Glenberg & Kaschak, 2002). Such findings are
      often attributed to mechanisms involving simulations of linguistically described
      events (Barsalou, 1999; Fischer & Zwaan, 2008). We propose that research
      paradigms in which simulation is the central focus need to be augmented with
      paradigms that probe the organization of the motor system during language
      comprehension. The use of well-studied motor tasks may be appropriate to this
      endeavour. To this end, we present a study in which participants perform a
      bimanual rhythmic task (Kugler & Turvey, 1987) while judging the plausibility of
      sentences. We show that the dynamics of the bimanual task differ when
      participants judge sentences describing performable actions as opposed to
      sentences describing events that are not performable. We discuss the general
      implications of our results for accounts of embodied cognition.

PMID- 19396733
TI  - Attentional capture by object appearance and disappearance.
AB  - In two experiments we examined whether the appearance of a new object has
      attentional priority over disappearance. Previous failures to show differences
      are possibly due to onsets and offsets always being presented as a sole visual
      transient. Rather than presenting each alone, we presented onset and offset
      singletons simultaneously with a display-wide luminance transient in order to
      force each to compete with other visual events. Results from Experiment 1 showed
      that targets associated with onsets accrued a reaction time benefit whilst
      targets associated with offsets did not. Experiment 2 showed that onsets
      attracted attention even when observers were attentionally set to look for
      offset. By contrast, offsets needed a relevant attentional set in order to
      attract attention. We argue that the appearance of an object has attentional
      priority over disappearance.

PMID- 19396734
TI  - Informatics and computation for drug discovery - specialist or mainstream tools?

PMID- 19396735
TI  - Pooling in high-throughput drug screening.
AB  - Pooling in HTS refers to the act of testing mixtures of compounds in a primary
      screen to accurately identify hits for secondary screening. The reduction in the
      number of tests needed to screen a compound library by pooling can also be
      extended to achieve much-needed error tolerance in HTS. Despite the success of
      HTS in other biological experiments, pooling in high-throughput drug screening
      has been a controversial and often marginalized paradigm. At first appearance,
      pooling appears to promise gains from reduced effort, or possibly could create
      more problems than solutions. However, this article demonstrates that pooling is
      a practical and necessary part of HTS: discussions include the rationale for
      pooling compounds in HTS, a unifying view of pooling design theory, a review of
      past attempts at pooling and their success, and recent advances in the field.

PMID- 19396736
TI  - A multiplexed approach to hit finding.
AB  - Assay formats and screening technologies can deliver more than one readout per
      measurement and therefore can be considered to be information-rich. This holds
      true for biophysical and selected biochemical assays, and in particular for
      cellular assay formats, where the term 'high-content assay' describes the most
      complex and advanced paradigm of small-molecule screening available to date.
      Given the multifactorial nature of the lead generation and optimization process
      in drug discovery, the enhanced information-density offered by multiplex
      screening technologies is considered to be beneficial to an informed hit
      selection for optimization. While hard evidence for an enhancement in hit and
      lead selection is only now emerging, multiplexed screening technologies will
      fulfill their promise in drug discovery if our understanding of target
      pharmacology and the complexity of biological systems can be advanced in
      parallel.

PMID- 19396737
TI  - Databases of protein-protein interactions and their use in drug discovery.
AB  - Proteins rarely act alone. With the development of experimental technologies,
      researchers have started to map the interactions of proteins in different
      organisms. The data gathered constitute potential frameworks for system-based
      drug discovery. The possibility of targeting protein-protein interactions with
      specific drugs raises expectations of huge impact in the therapeutics field,
      despite the large quantity of research still necessary to delineate the complete
      interactome of a single cell. This review summarizes some concepts relating to
      protein-protein interfaces in relation to drug discovery, and discusses studies
      aiming to develop protein-protein interaction modulators through the combination
      of in silico and in vitro screening experiments.

PMID- 19396738
TI  - Mining and visualizing the chemical content of large databases.
AB  - The shift in the drug discovery paradigm that has resulted in increased
      dependence on large volumes of information for decision making has created new
      challenges and opportunities in chemoinformatics research. The large volumes of
      data that are now available present an opportunity for the development of better
      predictive models, for the selection of more promising drug candidates, and for
      more comprehensive decisions to be made by researchers in chemistry and biology.
      The progress of this approach in drug discovery has also introduced challenges
      associated with the need to develop better tools to manage the large volumes of
      data. For chemistry-related research in particular, there is a need for more
      effective retrieval methods and better tools for data analysis that incorporate
      good interface design to facilitate the use of such systems by the non-expert
      scientist. This article reviews recent developments in the mining of large
      volumes of chemistry data, with a focus on chemoinformatics tools for small
      molecule drug discovery and tools developed for analysis and in-depth mining.
      External sources of data, such as a variety of web services, further expand the
      volume of data to be analyzed during any small-molecule discovery project. The
      impact of the generation of large volumes of data and the related research
      factors is reshaping chemoinformatics work.

PMID- 19396739
TI  - Mining chemical and biological information from the drug literature.
AB  - The mining of information from the drug literature covers a broad set of
      disciplines that include chemistry, biology and medicine. It is not possible for
      any one scientist to keep up to date on the wide breadth of published
      pharmaceutical information. The need for researchers to find and integrate
      information from the drug literature with other information is apparent. This
      article highlights some of the key themes of 2008 publications on mining chemical
      and biological information, and indicates that the drug literature has exhibited
      a significant transformation in 2008.

PMID- 19396740
TI  - Current developments in and importance of high-performance computing in drug
      discovery.
AB  - A number of current trends that are being adopted to reshape the field of high
      performance computing exist, including multi-core systems, accelerators, and
      software frameworks for large-scale intrinsically parallel applications. These
      trends intersect with recent developments in computational chemistry to provide
      new capabilities for computer-aided drug discovery. Although this review focuses
      primarily on the application domains of molecular modeling and biomolecular
      simulation, these computing changes are relevant for other computationally
      intensive tasks, such as instrument data processing and chemoinformatics.

PMID- 19396741
TI  - Virtual screening - what does it give us?
AB  - In current pharmaceutical research, lead compounds of high quality and structural
      diversity are key to the successful optimization of development candidates. In
      house compound libraries at pharmaceutical companies, tested using HTS assays,
      are the major source of leads for new projects. However, these physically
      existing compounds, stored in microtiter plates in dispensaries, represent only a
      tiny fraction of the drug-like chemical space. Virtual screening offers many
      possibilities for new structures beyond those found in in-house libraries. During
      the last decade, a huge number of different virtual screening methods have been
      reported and used to search for novel bioactive compounds for many targets. This
      review addresses the current status of virtual screening, highlighting
      achievements as well as challenges, along with the value of virtual screening,
      and recent examples of successful applications.

PMID- 19396742
TI  - New in protein structure and function annotation: hotspots, single nucleotide
      polymorphisms and the 'Deep Web'.
AB  - The rapidly increasing quantity of protein sequence data continues to widen the
      gap between available sequences and annotations. Comparative modeling suggests
      some aspects of the 3D structures of approximately half of all known proteins;
      homology- and network-based inferences annotate some aspect of function for a
      similar fraction of the proteome. For most known protein sequences, however,
      there is detailed knowledge about neither their function nor their structure.
      Comprehensive efforts towards the expert curation of sequence annotations have
      failed to meet the demand of the rapidly increasing number of available
      sequences. Only the automated prediction of protein function in the absence of
      homology can close the gap between available sequences and annotations in the
      foreseeable future. This review focuses on two novel methods for automated
      annotation, and briefly presents an outlook on how modern web software may
      revolutionize the field of protein sequence annotation. First, predictions of
      protein binding sites and functional hotspots, and the evolution of these into
      the most successful type of prediction of protein function from sequence will be
      discussed. Second, a new tool, comprehensive in silico mutagenesis, which
      contributes important novel predictions of function and at the same time prepares
      for the onset of the next sequencing revolution, will be described. While these
      two new sub-fields of protein prediction represent the breakthroughs that have
      been achieved methodologically, it will then be argued that a different
      development might further change the way biomedical researchers benefit from
      annotations: modern web software can connect the worldwide web in any browser
      with the 'Deep Web' (ie, proprietary data resources). The availability of this
      direct connection, and the resulting access to a wealth of data, may impact drug
      discovery and development more than any existing method that contributes to
      protein annotation.

PMID- 19396743
TI  - Acute antihypertensive therapy in pregnancy-induced hypertension: is nicardipine
      the answer?
AB  - Hypertensive disorders in pregnancy constitute one of the most frequent medical
      complications during gestation. Unfortunately, maternal and perinatal mortality
      remains significant worldwide in this population. Not infrequently, patients with
      severe preeclampsia will need parenteral agents to achieve rapid blood pressure
      control to avoid end-organ damage. During the last decades, new antihypertensive
      medications have become available for management of hypertensive crisis. One of
      these agents is the calcium channel blocker nicardipine. Nicardipine has been
      used extensively in different clinical settings including neurosurgery,
      cardiothoracic surgery, transplant medicine, and internal medicine patients.
      Minimal data exist in the literature regarding the use of this medicine during
      pregnancy. The purpose of this article is to review the pharmacological
      properties of nicardipine, the available literature regarding its use during
      pregnancy, and potential interactions with other medicines used commonly in
      preeclampsia, as well as potential side effects directly affecting the peripartum
      period.

PMID- 19396744
TI  - Fetal brain tumors: a review of 154 cases.
AB  - The purpose of this literature review is to describe the various types of brain
      tumors that occur in the fetus, their locations, initial findings, pathology, and
      outcome. Data are presented that show which patients are likely to survive or
      benefit from treatment compared with those who are unlikely to respond. An
      analysis is performed on patients with fetal brain tumors that were detected
      prenatally by imaging studies or discovered directly after birth. The review
      revealed 154 fetuses presenting with brain tumors. Teratoma was the leading
      neoplasm. Next was astrocytoma followed by craniopharyngioma, primitive
      neuroectodermal tumor, choroid plexus papilloma, meningeal tumors, and
      ependymoma. The most common presenting findings were macrocephaly and an
      intracranial mass. Overall hydrocephalus was next, followed by stillbirth. Most
      tumors were detected during the third trimester of pregnancy. Over a third of the
      affected fetuses were stillborn. Many tumors were inoperable as they occupied
      much of the intracranial cavity and involved large areas of the brain. Overall
      survival rate was 23/154, or 15%. Generally fetal brain tumors are associated
      with a poor prognosis.

PMID- 19396745
TI  - Hemodynamic differences in blood flow between free skin and muscles flaps:
      prospective study.
AB  - We used Doppler ultrasound to evaluate postoperative hemodynamic changes in blood
      flow in skin (n = 11) and muscle (n = 4) flaps. The minimum velocities,
      resistance indexes, and diameters of the pedicle, the recipient, and control
      artery (the corresponding contralateral artery that served as a recipient vessel)
      were recorded intraoperatively and at 10 days, 1 month, 3 months, 6 months, and
      12 months after surgery. The minimum velocities and blood flow in recipient and
      pedicle arteries in both groups increased after flap transfer. In control
      arteries, these values decreased over the follow-up period. The decrease of blood
      flow in recipient arteries for the skin flaps started at 10 days and in the
      muscle flap at 1 month. The decrease in minimum velocity was noted after 10 days
      and 1 month for skin and muscle flaps, respectively. Resistance indexes were
      higher in skin flaps (99 +/- 6) compared with muscle flaps (89 +/- 9). Also,
      recipient blood flow after flap transfer, independent from intraoperative values,
      changed according to flap size; muscle flaps that were larger than skin flaps
      caused significantly higher blood flow in recipient artery.

PMID- 19396746
TI  - The short- and long-term effects of Seprafilm on peripheral nerves: a
      histological and functional study.
AB  - Extraneural scar reduction is an important goal in peripheral nerve microsurgery.
      The use of biosynthetic materials, such as Seprafilm , reduces postoperative
      adhesions in abdominopelvic gynecologic and orthopedic surgery. The study
      evaluates the safety of Seprafilm in proximity to nerve tissue in a noninjury
      (phase 1) and injury (phase 2) model. Phase 1 groups were: (1) sciatic nerve
      exposure and neurolysis (n = 15), (2) Seprafilm placement superficial to the
      nerve (n = 15), and (3) circumferentially wrapping Seprafilm around the nerve (n
      = 15). Outcome measures at 45 and 90 days included wound inspection,
      histomorphometry, and stereological analysis of vascularity. Phase II groups
      were: (1) sciatic nerve cut and repair alone (n = 15) or (2) nerve wrapped with
      Seprafilm (n = 15). Nerves were evaluated at 18, 32, and 42 days postoperatively,
      and animals underwent biweekly functional walking tracks. In phase I, no
      significant differences were detected between groups. In phase II, fewer
      perineural scar bands were seen with Seprafilm . Histomorphometric differences
      favoring Seprafilm at 18 days and favoring control at 42 days were noted ( P <
      0.05), though no differences in functional outcomes were detected. Qualitatively
      less perineural scar tissue was seen when using Seprafilm . No functional or
      histological deleterious effects were noted from placing Seprafilm on intact
      nerves or cut and repaired nerves.

PMID- 19396747
TI  - Inflammatory myofibroblastic tumor as adverse outcome of eosinophilic
      esophagitis.

PMID- 19396748
TI  - Identification of vertebral deformities in the Polish population by morphometric
      X-ray absorptiometry - results of the EPOLOS study.
AB  - INTRODUCTION: The aim of the study was the determination of the prevalence of
      asymptomatic vertebral deformities in healthy persons of the Polish population,
      based on morphometric X-ray absorptiometry (MXA), and comparison of the results
      with data from literature, obtained by other techniques. MATERIAL AND METHODS:
      The study involved 829 persons, including 520 women and 309 men, aged 18-79
      years, untreated for osteoporosis before. The Th(4) to L(4) vertebrae were
      examined. Lateral scans of the thoracic-lumbar spine were made by an Expert-XL
      densitometer. Six point digitization was used to calculate the anterior (Ha),
      central (Hc), and posterior (Hp) height of the Th(4)-L(4) vertebral bodies. The
      vertebrae were defined as having prevalent deformities when at least one ratio
      value (Ha/Hp, Hc/Hp, Hp/Hp up, or Hp/Hp low) fell 3 SDs below or even more than
      the reference mean of that ratio at any vertebral level. RESULTS: The analysis
      was performed on 9629 vertebrae, of which 167 (1.75%), evaluated as deformed and
      considered as fractures, were observed in 113 patients (13.63 % of the examined
      patients). In 81 persons (74% of the patients with fractures; 9.7% of the studied
      population), single fractures were demonstrated, while in 28 persons, multiple
      deformities prevailed. Fractures occurred in 108 women (20.7% of the examined
      women) and 42 men (13.5% of the examined men). The highest incidence of
      deformities was observed in women over 55 years of age. First-degree deformities
      dominated. Deformities of the Th(8) and Th(6) vertebrae were most frequently
      observed. CONCLUSIONS: 1. Using MXA, it was found that in the Polish population
      deformities of vertebrae are common, as was demonstrated in X-ray morphometric
      studies in the European Vertebral Observation Study (EVOS). 2. Densitometric
      morphometry, as a non-invasive technique, may become a useful tool in the
      diagnostics of vertebral fractures.

PMID- 19396749
TI  - Compliance with alendronate 10 treatment in elderly women with postmenopausal
      osteoporosis.
AB  - INTRODUCTION: It has been shown that more than 50% of people with a chronic
      disease, including osteoporosis, discontinue treatment during its first year.
      This problem increases with the time of observation. The aim of this study was to
      assess alendronate compliance over a period of 6 or 18 months in clinical
      practice of postmenopausal osteoporosis. MATERIAL AND METHODS: Using a
      retrospective study of clinical histories (357) obtained in our Outpatient
      Clinic, as well as telephone interviews with patients, the compliance with
      alendronate therapy in postmenopausal patients was assessed. RESULTS: After 1.5
      years on observation 20.4% of patients, and after 0.5 years 8.5% of patients,
      discontinued their treatment as a result of intolerance (especially side effects
      on the gastrointestinal tract) (47.8%), health problems unrelated to osteoporosis
      (8.7%), inconvenience of the daily regimen (13.1%), costs (4.3%), and improvement
      of clinical condition (26.1%). It is worth mentioning that in both periods of
      observation (1.5 and 0.5 years) almost the same percentage of patient
      discontinued visits at our Outpatient Clinic (15.6% and 14.4%, respectively).
      Telephone interviews with patients who stopped attending the Outpatient Clinic at
      the Regional Centre of Menopause and Osteoporosis revealed that more than 50% of
      them discontinued the treatment. CONCLUSIONS: Not all patients treated with
      alendronate are compliant. Osteoporosis is a chronic disease, which needs long
      clinical observation and constant adherence to medication. Effective
      communication between doctor and patient, and follow-up visits that are more
      frequent would greatly improve the adherence to osteoporosis treatment
      modalities. Compliant patients achieved increases in bone mass density with
      simultaneous fracture risk reduction.

PMID- 19396750
TI  - WHO fracture risk calculator (FRAX) in the assessment of obese patients with
      osteoporosis.
AB  - INTRODUCTION: Recently, a new fracture risk-assessment calculator (FRAX) has been
      introduced. The aim of this study was to assess its usefulness for the re
      assessment of fracture risk in obese patients and re-assignment to treatment.
      MATERIAL AND METHODS: 350 obese female patients were included. In all of them, 10
      year fracture risk was calculated using FRAX (with and without T score value).
      RESULTS: If major osteoporotic fracture risk was calculated with BMD, it was low
      in most of the patients (in 82.1% of those treated, and in 95.9% of those not
      treated it was below 10%). Mean risk values were significantly higher in the
      treated (7.7 [3;39]%) than in the non-treated group (4.6 [2.1;14]%). The reason
      for start of treatment in 95 out of 106 patients was a sustained low-energy
      fracture, low BMD, or both. CONCLUSIONS: The WHO fracture risk calculator may be
      a useful tool in treated obese females with osteoporosis. The information
      regarding 10-year fracture risk may change the treatment strategy at least for
      those in whom the decision of treatment was based solely on low BMD.

PMID- 19396751
TI  - [Utility of laboratory tests in evaluation of fracture risk and in differential
      diagnostics of low bone mass in asymptomatic postmenopausal women].
AB  - INTRODUCTION: Until now, there are no specific guidelines for laboratory
      evaluation in asymptomatic patients with low bone mineral density (BMD). The aim
      of the study was to estimate the utility of laboratory tests in evaluation of
      fracture risk and in differential diagnostics of low bone mass in asymptomatic
      postmenopausal women. MATERIAL AND METHODS: That was a retrospective study of 207
      women. The results of laboratory investigations, densitometry and thoracic lumbar
      X-rays were analyzed. The relationship between BMD, vertebral fractures and
      abnormal lab tests was investigated. In patients with low BMD, reasons of this
      pathology was determined and costs of differential diagnostics were estimated.
      RESULTS: There were no differences in prevalence of abnormal lab tests in women
      with BMD that met and didn't meet densitometry criteria of osteoporosis (85.05%
      vs. 82.00%). Similarly, in people with and without vertebral fractures (84.44%
      vs. 86.27%). There was no relationship between osteoporosis and abnormal tests
      except of high PTH in the group with vertebral fractures. In 64% of women, the
      cause of low BMD was asymptomatic pathology other then primary osteoporosis -
      most often vitamin D deficiency (52.0%). Costs of lab tests used in differential
      diagnostics were between 45 and 153 PLN, person and 182.50-409.10 PLN per
      diagnosis. CONCLUSIONS: 1. Laboratory tests aren't useful to assess fracture
      risk. 2. In 64% of asymptomatic postmenopausal women with low BMD, the cause of
      this abnormality may by pathology that coexists with primary osteoporosis. 3. To
      assess the cause of low BMD, except basic lab tests, 25(OH)D should be tested.

PMID- 19396752
TI  - [Influence of weight reduction on leptin concentration and bone mineral density
      in patients with morbid obesity before and 6 months after bariatric surgery].
AB  - INTRODUCTION: Leptin is considered to exert dual effect on bone metabolism:
      anabolic (through peripheral pathways) and antiosteogenic (through central
      nervous system). The total leptin's effect on bone is not known. The aim of the
      study was to examine bone metabolism and leptin concentration in patients with
      morbid obesity before and after bariatric surgery (BS). MATERIAL AND METHODS:
      Forty one patients with morbid obesity selected for BS were included in the
      prospective study. Body mass index (BMI), serum leptin, parathyroid hormone
      (PTH), 25-hydroxy vitamin D (25(OH)D) concentrations and bone mineral density
      (BMD) in the lumbar spine (LS) and proximal femur (PF) were examined before and 6
      months after BS. RESULTS: Before operation (mean BMI 44.0 kg/m(2)) mean leptin
      and PTH concentration was increased (accordingly 37.1 ng/ml and 82.7 pg/ml), mean
      25OHD concentration was decreased to 4.3 ng/ml. Mean BMD was within the upper
      limit of the population reference range. Leptin concentration was positively
      correlated with BMI. There was no correlation of leptin with BMD (in LS and PF),
      PTH and 25(OH)D. Following the operation (mean BMI 31.8 kg/m(2)) mean leptin
      concentration decreased by 30.6 ng/ml (p < 0.001), PTH decreased by 38.9 pg/ml (p
      < 0.001), 25(OH)D increased by 2.1 ng/ml (NS). Mean BMD in LS increased by 0.067
      g/cm(2) (p < 0.005), in PF decreased by 0.044 g/cm(2) (p < 0.02). Leptin was
      positively correlated with BMI but not with BMD (in both sites), PTH, 25(OH)D.
      CONCLUSIONS: Weight loss in patients with morbid obesity after BS leads to
      decrease in serum leptin, increase in BMD in LS and decrease in PF. These changes
      are accompanied by regression of hyperparathyroidism, which is probably secondary
      to vitamin D deficiency.

PMID- 19396753
TI  - [Klotho - a new regulator of mineral homeostasis].
AB  - Research on the regulation of mineral homeostasis have been continuing for the
      decades, with an effect of establishing the impression that the governing
      mechanisms are already fairly well known and understood. Revealing of the
      molecular mechanism of action of the Klotho protein, forced us to revise this
      knowledge. It is known already that Kloto is a unique regulatory efector playing
      key role in reversing the imbalanced extracellular Ca(++) concentrations, by
      affecting the intensity of the transepithelial transport and modulation of the
      parathormone excretion. In cooperation with the phosphaturic hormone - Fgf23 it
      regulates calcium concentration by suppression of 1,25(OH)(2)D synthesis, and
      reabsorption of phosphate in a distal convoluted part of nephron. Acting through
      these mechanisms Klotho takes part in the regulation of the mineral homeostasis
      of cerebrospinal fluid, blood and body fluids acting on the choroid plexus,
      parathyroid glands and distal convoluted nephrons. In that way Klotho becomes one
      of the main players in a complex and multilevel system of maintaining the mineral
      homeostasis of the organism.

PMID- 19396754
TI  - [Senile osteoporosis].
AB  - The presented paper aims to summarize knowledge regarding senile osteoporosis.
      The article highlights high prevalence of the disease and the burden caused by
      osteoporotic fractures on the healthcare system. It describes shortly a complex
      ethiopathogenesis, in which vitamin D deficiency, other hormonal disturbances,
      protein-energy malnutrition, dysfunction of neuromuscular system and other
      factors may play a role. Possible diagnostics (x-rays, dual x-ray absorptiometry,
      10-years fracture risk) and therapeutic methods are also presented.

PMID- 19396755
TI  - [Effects of biologic antirheumatic treatments on bone metabolism in rheumatoid
      arthritis and ankylosing spondylitis].
AB  - Systemic inflammatory disorders like rheumatoid arthritis (RA) and ankylosing
      spondylitis (AS) are characterized by extensive dysregulation of bone metabolism
      recognized as focal articular bone erosions, juxta-articular and systemic bone
      loss. The complex interactions between bone cells, osteoprotegerin/RANKL pathway
      and a variety of inflammatory mediators are involved in the pathogenesis of focal
      and systemic osteopenia. Treatments with TNF-alpha blockers inhibit inflammation
      induced bone resorption and might prevent structural bone damage in RA. In some
      studies with anti-TNF agents, an increase in BMD has been documented in
      spondyloarthropathies and in RA. The B-cell depleting antibody rituximab and the
      T-cell costimulation blocker abatacept are emerging as other effective treatment
      options in RA. Studies with anti- RANKL antibody Denosumab in RA demonstrate,
      that treatment targeting RANKL prevents development of erosions but not
      inflammation. This article reviews recent scientific literature regarding the
      effects of modern targeted therapies on bone turnover, bone mass and focal damage
      of joints.

PMID- 19396756
TI  - Critical points in strategies for the diagnosis and treatment of osteoporosis.
AB  - Current treatment decisions for osteoporosis depend on the fracture risk
      calculated based on the results of comprehensive diagnostic procedures [clinical
      risk factors (CRF), densitometry (BMD), morphometry, and bone turnover markers
      (BTM)]. Recently developed fracture risk assessment tool (FRAX) represents an
      important new achievement as a 10-year fracture risk calculation based on femoral
      neck densitometry and age combined with independent clinical fracture risk
      factors. FRAX presents several options: FRAX BMI (body mass index) is advocated
      as a helpful screening tool to identify the group of patients with high fracture
      risk, independently of access to densitometry and FRAX, utilizing hip
      densitometry. In both cases, the probability of major fractures or hip fractures
      are calculated during performed diagnostic evaluations. Operating FRAX algorithm
      does not include spinal bone mineral density, which is its main limitation. With
      the aim of improvement of anti-fracture efficacy of therapeutic management of
      osteoporosis, we have extended our discussion to three integral elements of
      existent strategy: 1) screening outlines, 2) principles of drug selection, and 3)
      treatment benefit evaluation. Since osteoporosis is a chronic disease, long-term
      adherence to the treatment is important. The suitability of the drug, the
      patient's preference, tolerability, and convenience should all be considered.
      Anti-catabolic drugs are most appropriate in patients with high bone turnover,
      while anabolic drugs demonstrate efficacy irrespective of bone turnover. BMD
      measurement is most widely used for long-term assessment of the efficacy of
      osteoporosis treatment. The measurements of bone turnover markers (BTMs) can be
      considered a useful shortterm (at 3 months) monitoring tool in selected patients.
      In both BTM and BMD, the least significant change (LSC) method should be used for
      interpretation of the results. Fractures are not a reliable clinical endpoint for
      evaluating the effectiveness of therapy in individual patients because of their
      stochastic nature. If fractures occur, however, the need for drug change and
      additional non-pharmacological treatment (fall prevention, balance training,
      muscle strengthening) should always be considered.

PMID- 19396757
TI  - [Mechanisms of action of anticatabolic drugs used in osteoporosis therapy].
AB  - Bone remodeling is essential for skeletal and the whole body health. Imbalance in
      skeletal turnover, so that bone resorption exceeds bone formation, may lead to
      reduction in bone strength and increase fractures risk. The main target of
      anticatabolic therapy is to normalize increased osteoclasts activity and bone
      turnover. Molecular mechanisms of action of this class of drugs are related with
      different points in cellular signaling pathways that control osteoclasts
      differentiation and resorbing activity. These mechanisms are briefly described in
      our review.

PMID- 19396760
TI  - [Validation of the Spanish version of the attention deficit hyperactivity
      disorder adult screening scale (ASRS v. 1.1): a novel scoring strategy].
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a common
      neuropsychiatric disorder in the adulthood. It's diagnosis is a complex process
      in which a screening tool can be useful. AIM: To analyze the six-question Adult
      ADHD Self-Report Scale (ASRS v. 1.1) validity in an outpatient clinical context.
      SUBJECTS AND METHODS: We performed a case-control study, involving 90 patients
      with ADHD and 90 controls without ADHD. They were outpatient treated in a program
      for adults ADHD in a hospital. The clinical disorder diagnosis was measured by
      the Conners Adult ADHD Diagnostic Interview. We analyzed the test accuracy for
      different ways to score and cut-offs. RESULTS: We found the best psychometric
      characteristics of ASRS v. 1.1 using a quantitative ranking between 0 and 24
      points, setting as cut-off 12 points. We observed a sensitivity of 96.7%,
      specificity 91.1%, positive predictive value 91.6% negative predictive value
      96.5%, kappa index 0.88 and area under the curve 0.94 (odds ratio = 297.3; 95%
      confidence interval = 76.2-1,159). CONCLUSION: The ASRS is a valid and useful
      tool for the adult ADHD screening in the clinical context.

PMID- 19396761
TI  - [Cognitive evoked potentials in remitting-relapsing and benign forms of multiple
      sclerosis].
AB  - INTRODUCTION: The assessment of the cognitive impairment in the multiple
      sclerosis disease is one of the most relevant challenges nowadays. An essential
      objective is to obtain diverse approaches that allow valuing objectively this
      impairment and its correlation with physiological variables. AIM: To analyze the
      possible modulations in physiological components of the information processing
      (ERPs) related with an attentional deficit in diverse classes of patients with
      multiple sclerosis. SUBJECTS AND METHODS: 17 patients with remitting-relapsing
      multiple sclerosis, 9 patients with benign multiple sclerosis and 19 healthy
      subjects participated in the study. Behavioral performance in a visuo-spatial
      task (Posner paradigm) and later, an auditory oddball test was carried out where
      electroencephalography signal was registered to obtain ERPs. Correlation analyses
      were calculated between patient variables (EDSS or disease duration) and
      psychophysiological variables. RESULTS: A delay in the reaction time during the
      development of the Posner task and a delay in the latency of the component P3
      during the realization of the oddball task were found in both groups of patient
      with multiple sclerosis. CONCLUSION: The data obtained in this experiment confirm
      the presence of attentional impairment in patients with diverse forms of multiple
      sclerosis. The exclusive modulation of the P3 latency component suggests that the
      impairment in these patients, at the beginning of the disease, is localized at a
      central level of cognitive processing and is product of the demyelinating
      process.

PMID- 19396762
TI  - [Comparative analysis of occupational therapy benefits in spastic patients with
      hands involvement before and after botulinum toxin infiltration].
AB  - INTRODUCTION: Spasticity is the most difficult motor disorder to be treated after
      an encephalic vascular accident or stroke, which interferes in the patient's
      selective motor functioning. AIM: To compare the involvement type of the
      extrinsic muscles, the functionality degree of the hand and functional
      independence of patients with spastic hemiplegia due to stroke after botulinum
      toxin A (BTA) infiltration. They were divided into a group receiving occupational
      therapy treatment (group I), and other who has not received it (group II).
      PATIENTS AND METHODS: Longitudinal study with 20 spastic hemiplegic outpatients
      due to stroke, both sexes, with average age of 53.1 +/- 15.3 years-old who have
      been attending in the botulinum toxin service. They have received BTA
      infiltration in the muscles responsible for the hand functional movements, and
      they were evaluated before and after 3-months infiltration. To collect data,
      these instruments were used: anamnesis questionnaire of occupational therapy, the
      Classification of involvement types of extrinsic muscle, according to adapted
      Zancolli, the adapted Hausen's Functional Classification, the Functional
      Independence Measure Scale, the Rivermead's Scale of Activity of Daily Life and
      the Barthel Index. RESULTS: In the classification, according to adapted Zancolli,
      group I presented higher improvement of involvement than group II. Statistical
      significance (p < 0.05) was observed in group I according to the other
      evaluations, except in the Barthel Index. CONCLUSION: Both effectiveness and
      importance of occupational therapy were observed in the rehabilitation of
      patients with spastic hemiplegia due to stroke after infiltration of BTA
      providing them greater abilities and functional independence in their daily life
      activities.

PMID- 19396763
TI  - [Cystic hemangioblastoma of the junction of the medulla and upper spinal cord
      associated to von Hippel-Lindau disease. Two case reports and a review of the
      literature].
AB  - INTRODUCTION: Hemangioblastomas are very highly vascularised benign tumours that
      can present either sporadically or in association with von Hippel-Lindau syndrome
      in 20% of cases. Only 5-20% of hemangioblastomas are located in the brainstem,
      and those that occur at the junction of the medulla and upper spinal cord are the
      ones that are less commonly diagnosed. CASE REPORTS: Two young patients were
      diagnosed with von Hippel-Lindau disease after beginning with a cystic
      hemangioblastoma at the junction of the medulla and upper spinal cord as the
      first pathological manifestation. Both of them underwent a suboccipital
      craniotomy and the two lesions were completely removed without any kind of post
      operative neurological deficits. One of the patients required a reintervention
      some years later due to a new recurrence of a symptomatic hemangioblastoma in the
      dorsal medulla. The genetic study conducted in both patients confirmed the
      presence of a mutation in the VHL gene, which is responsible for the syndrome
      they were suffering from. CONCLUSIONS: The presence of cystic hemangioblastomas
      of the junction of the medulla and upper spinal cord associated to von Hippel
      Lindau disease is very rare. Despite the technical difficulties involved in
      removing them, the incorporation of the latest neuroimaging and microsurgery
      techniques has made it possible to significantly reduce the morbidity and
      mortality rate associated to the surgical treatment of such patients.

PMID- 19396764
TI  - [Drugs for attention deficit hyperactivity disorder].
AB  - Quantitative studies have highlighted differences in several drugs approved for
      use in Spain in the treatment of attention deficit hyperactivity disorder. No
      clear differences are observed, however, in the case of qualitative studies. The
      number of patients needed to be treated in order for one to reach complete
      remission (NNT) of methylphenidate (MTF) is from 2.2 to 5, and the effect size
      (ES) is 0.9. Atomoxetine has an NNT of 4 and an ES of 0.7. The advantages of
      immediate-release MTF (IR-MTF) over the extended-release version (ER-MTF) lie in
      its low cost, its flexibility and the better results obtained in quantitative
      studies. In contrast, ER-MTF offers a lower risk of abuse, needs to be taken
      fewer times with less need for third parties to control administration, and there
      is a lower risk of stigmatisation. Combination or changes of IR-MTF and ER-MTF
      and the combination of MTF with atomoxetine are sometimes necessary to adjust the
      weekday or weekend doses. Starting treatment with IR-MTF and then maintaining or
      changing to ER-MTF offers certain advantages as regards safety, dose adjustments
      and dosage. Atomoxetine is the best alternative if there is a background of
      adverse events with low or moderate doses of stimulants, or lack of response to
      high doses of stimulants. In cases of notable comorbid anxiety, both MTF and
      atomoxetine have the same level of indication. If there is a risk of substance
      abuse, both atomoxetine and ER-MTF are the preferred treatment. For the other
      indications, MTF is the preferred treatment.

PMID- 19396765
TI  - [The value of genetic and neuroimaging studies in the differential diagnosis of
      Parkinson's disease].
AB  - INTRODUCTION: Parkinson's disease (PD) is usually diagnosed on the basis of
      clinical criteria. Today there are genetic and neuroimaging tests that can make a
      valuable contribution to the study of this disease. AIMS: To review the recent
      advances in genetic studies and in neuroimaging techniques applied to PD, as well
      as looking at their shortcomings, and to analyse the reasons for conducting such
      tests and to discuss their importance in everyday clinical practice, including a
      series of reflections on ethical issues. DEVELOPMENT: The list of genetic
      disorders associated with PD is continually being extended and reviewed, and
      pathological alterations have been defined in at least 10 genes. The most
      frequent mutations in our setting are to be found in the parkin gene (PARK2) and
      in the LRKK2 gene (PARK8). These mutations have a penetrance that is not very
      high and their clinical expression is variable. Images obtained by nuclear
      resonance, single-photon emission tomography, positron emission tomography or by
      cranial sonography provide data that can help in the diagnosis of PD and to
      differentiate it from other diseases. None of the techniques is wholly specific,
      however, and there are clinico-radiological disagreements. CONCLUSIONS: The
      detection of mutations does not allow a clear prognostic differentiation or a
      distinct therapeutic attitude to be established. The value of neuroimaging
      techniques in very early phases and in dubious cases is still not altogether
      clear. Whether establishing a diagnosis in very early phases currently offers the
      patient any benefits is subject to debate. It would be advisable to attempt to
      distinguish between tests that are carried out for clinical reasons and those
      which are conducted for research purposes so as to be able to proceed in the most
      suitable manner.

PMID- 19396766
TI  - [Consensus clinical practice guidelines of the Andalusian Epilepsy Society:
      therapeutic recommendations when dealing with a first epileptic seizure and in
      epileptic status].
AB  - INTRODUCTION: Most epileptic seizures are brief and self-limiting, but sometimes
      they can last longer than expected and this entails (in the case of generalised
      seizures) a high risk of morbidity and mortality, which increases as they get
      longer. This severity justifies the need to draw up a set of consensus-based
      practice guidelines based on implicit evidence, to use Liberati's nomenclature,
      concerning aspects related to the recommended therapeutic management of a patient
      with prolonged seizures who is being attended in an emergency department.
      MATERIALS AND METHODS: A selective search was conducted on PubMed-Medline for
      scientific information related to the subject using scientific evidence filters.
      This search was completed in other scientific evidence search engines, such as
      Tripdatabase, Biblioteca Cochrane Plus or DARE. The selected references were
      analysed and discussed by the authors, and the available evidence and any
      recommendations that could be drawn from it were collected. RESULTS: The search
      revealed the existence of 33 primary documents and six practice guidelines or
      protocols related with the topic under study. The recommendations were inserted
      in the text explicitly. CONCLUSIONS: The therapeutic protocol must be started
      when faced with any seizures that last more than five minutes. First, steps must
      be taken to ensure proper respiratory and cardiocirculatory functioning, and then
      fast-acting antiepileptic drugs are administered intravenously and in high doses
      until the cause is identified and controlled. Due to their lower level of
      morbidity and mortality, prolonged non-convulsive seizures do not generally
      require therapy that is so vigorous and with such a high risk of complications.

PMID- 19396767
TI  - [Subcortical focal heterotopias: their different sizes].

PMID- 19396768
TI  - [Neurodegeneration due to accumulation of iron, sepsis, dysautonomia and death].

PMID- 19396769
TI  - [Supranuclear downward gaze palsy secondary to a cardioembolic cerebrovascular
      accident in the thalamus].

PMID- 19396770
TI  - [Neuropsychological profile in musical hallucinations in the elderly].

PMID- 19396771
TI  - [Spectrum of benign monomelic amyotrophy clinical presentation].

PMID- 19396772
TI  - [Idiopathic intracranial hypertension as the presenting symptom of Addison's
      disease].

PMID- 19396773
TI  - [The value of motor evoked potentials in spine surgery].

PMID- 19396774
TI  - Clinical efficacy of a Ginkgo biloba extract in the topical treatment of allergic
      conjunctivitis.
AB  - PURPOSE: To investigate the clinical efficacy of a Ginkgo biloba extract
      associated with hyaluronic acid ophthalmic solution (GB-HA, Trium, SOOFT, Italy),
      compared to hyaluronic acid ophthalmic solution (HA) alone, in seasonal allergic
      conjunctivitis (AC). METHODS: A total of 60 patients with symptomatic AC were
      enrolled and randomly assigned to the two treatment regimens. After a washout
      period of 15 days, the treatment with GB-HA eyedrops or HA ophthalmic solution
      alone was initiated and continued for 1 month. The clinical symptoms such as
      conjunctival hyperemia, conjunctival discharge, and chemosis, and subjective
      signs as itching, photophobia, stinging, and lacrimation, were evaluated before
      and after the treatment. A 0-4 score was used by an independent clinical observer
      to quantify the above parameters. RESULTS: Patients treated with GB-HA, compared
      to patients treated with HA alone, showed a significant decrease in the
      appearance of conjunctival hyperemia, conjunctival discharge, and chemosis.
      Furthermore, all patients treated with GB-HA showed a significant improvement of
      subjective symptoms, compared to HA patients. Compared to their baseline values,
      patients treated with HA alone showed a small but not significant improvement in
      only some of the clinical and subjective symptoms. CONCLUSIONS: The results
      suggest that Ginkgo biloba extract may exert therapeutic activity in the
      treatment of seasonal allergic conjunctivitis. Hyaluronic acid did not exert any
      valuable effect on this pathology.

PMID- 19396775
TI  - Antioxidants intake and dry eye syndrome: a crossover, placebo-controlled,
      randomized trial.
AB  - PURPOSE: To assess whether an orally administered antioxidant dietary supplement
      could improve the objective clinical signs and alleviate the subjective symptoms
      of dry eye syndrome. METHODS: Twenty-four subjects diagnosed with dry eye
      syndrome were randomized in a crossover, double-blind, controlled, randomized
      study to receive a placebo or an antioxidants combination (Oxybiane) for 12
      weeks. In all subjects, break-up time (BUT) test, Schirmer test, ocular symptoms
      (sore eyes, burning, itching, sensation of foreign object in the eye,
      photophobia, sticky eyes, and redness), visual comfort, and general well-being
      were evaluated weekly. RESULTS: After 12 weeks of supplementation with Oxybiane,
      both the BUT scores (27.3%+/-8.4% with Oxybiane versus 3.61%+/-4.3% with the
      placebo, p=0.017) and the Schirmer scores (26.9%+/-14.2% with Oxybiane versus 
      4.7%+/-3.4% with the placebo, p=0.037) were significantly increased. A
      significantly improvement was also observed considering subjective clinical
      symptoms such as burning (p=0.031), itching (p=0.027), sensation of foreign body
      in eye (p=0.030), and redness (p=0.043). CONCLUSIONS. Supplementation with oral
      antioxidants can improve both tear stability and quantity but also subjective
      clinical signs.

PMID- 19396776
TI  - Why do patients with improved visual acuity drop out of RGP contact lens use? Ten
      year follow-up results in patients with scarred corneas.
AB  - PURPOSE: To evaluate the long-term results of rigid gas permeable (RGP) contact
      lenses and to investigate the reasons for patient dissatisfaction with this
      therapy. METHODS: Records of 17 patients (20 eyes) who started using RGP contact
      lenses for correction of irregular astigmatism due to scarred corneas between
      1995 and 1996 were evaluated retrospectively. Best-corrected visual acuities with
      or without RGP contact lenses were noted. The mean duration of contact lens use,
      reasons for discontinuation of therapy, and treatment methods preferred over
      contact lens use were evaluated. RESULTS: The irregular astigmatisms were induced
      by herpetic keratitis (3 eyes), corneal trauma (5 eyes), and previous corneal
      infections (12 eyes). All of the patients had increase in visual acuity with RGP
      contact lenses (p=0.000). At the end of the follow-up it was found that only one
      patient was still using RGP contact lenses (5%). The mean duration for contact
      lens use was 21.42+/-4.53 SE months (2-72 months). The reasons for dropping out
      contact lenses were intervening surgical procedures (57.8%), loss of patient
      motivation (26.3%), recurrent punctate epitheliopathy (10.5%), and herpes simplex
      keratitis reactivation (5.2%). CONCLUSIONS: RGP contact lens use is a successful
      method of increasing visual acuity in scarred corneas. However, patients with
      good visual acuity in the fellow eye find it hard to remain motivated for RGP
      contact lens use in the unhealthy eye. Furthermore, patients prefer permanent
      treatment methods even though these methods would result in decreased visual
      acuity.

PMID- 19396777
TI  - In vivo laser confocal microscopic findings in patients with epithelial basement
      membrane dystrophy.
AB  - PURPOSE: To evaluate the corneal characteristics of patients with epithelial
      basement membrane dystrophy (EBMD) using an in vivo laser confocal microscope,
      Heidelberg Retina Tomograph II, Rostock Cornea Module (HRT II RCM). METHODS:
      Sixteen women and 13 men who were diagnosed with or suspected to have EBMD were
      included in the study. The mean age of the patients was 56.4+/-17.2 years within
      a range of 25 to 81 years. Nine patients (31%) had a history of recurrent corneal
      erosions and 3 patients had been misdiagnosed with herpetic epithelial keratitis.
      The remaining 17 patients were asymptomatic and EBMD was diagnosed incidentally
      during routine eye examinations. RESULTS: Confocal microscopy revealed highly
      reflective tissue in various configurations within the intermediate and basal
      epithelial cell layers corresponding to the abnormal basement membrane extending
      into the epithelium. There were thin, parallel hyperreflective lines and high
      contrast round lesions in sizes ranging between 10 and 250 microm within the
      epithelium. Basal epithelial cells around the abnormal basement membrane and
      cysts seemed to be highly distorted. In two subjects with bleb-like disorder, the
      authors observed circular or oval hyporeflective areas with a diameter ranging
      between 40 and 100 microm at the level of basal epithelium and the Bowman layer,
      accompanied by hyperreflective, linear structures extending into the epithelium.
      CONCLUSIONS: EBMD is most commonly asymptomatic and undiagnosed; however, it
      might be associated with recurrent corneal erosions and lead to severe
      complications after LASIK surgery. The confocal images are highly characteristic
      for EBMD; therefore, confocal microscopy seems to be a valuable tool in the
      diagnosis of EBMD.

PMID- 19396778
TI  - Epidemiologic aspects and clinical outcome of fungal keratitis in southeastern
      Brazil.
AB  - PURPOSE: Fungal keratitis (FK) is a sight-threatening disease, more prevalent in
      developing regions. The present retrospective study was conducted in order to
      evaluate the epidemiologic and clinical aspects and the progression of FK in
      patients treated at two ophthalmologic reference centers in Southeast Brazil.
      METHODS: The charts of patients with infectious keratitis treated between 2000
      and 2004 were reviewed. For the 66 cases of FK confirmed by microbiological
      analysis, data related to patient, disease, and therapeutic approaches were
      obtained. RESULTS: Mean patient age was 40.7+/-16 years. Fifty-three were men and
      13 were women. Ocular trauma occurred in 40% of cases (27). Previous medications
      taken by the patients were quinolone in 72.5% and antimycotics in 30%. Visual
      acuity (VA) at presentation was >0.3 in 16% and <0.1 in 74.5%. Penetrant
      keratoplasty was performed in 38% and evisceration in 15%. The causing agents
      were Fusarium sp in 67%, Aspergillus sp in 10.5%, and Candida sp in 10%.
      Medication alone resolved 39% of cases within a mean period of 24.5+/-12 days.
      Final VA was >0.3 in 28%, and <0.1 in 63%. CONCLUSIONS: Fungal keratitis
      presented as a disease with severe complications, predominantly among young
      males, and was mostly caused by filamentous fungi. The present information
      permits the establishment of preventive strategies. Reducing the time between
      onset and treatment and using more accessible specific medication would reverse
      the negative prognosis.

PMID- 19396779
TI  - Repeat penetrating keratoplasty: indications and prognosis, 1995-2005.
AB  - PURPOSE: To evaluate the data of penetrating keratoplasty over a 10-year period
      and to compare indications and outcomes of eyes undergoing single graft with
      those of eyes requiring regrafting. METHODS: A total of 652 eyes of 613 patients
      required single graft (Group I). Sixty-one regrafts were performed on 53 eyes
      (Group II). The mean follow-up time was 23.4+/-21.3 months (range 6-132 months).
      The results were evaluated for the following criteria: primary indications,
      allograft reactions, graft clarity, final postoperative visual acuity, and
      complications leading to reduction in vision. RESULTS: The most common indication
      was keratoconus (228 eyes; 35.0%) in Group I, and vascularized corneal scar (12
      eyes; 22.6%) in Group II. Allograft reactions occurred in 96 eyes (14.7%) in
      Group I, and 17 eyes (32.0%) in Group II (p=0.001). At the end of the study
      period, 76.4% of patients in Group I had entirely clear grafts, whereas 45.3% of
      patients in Group II had entirely clear grafts (p=0.000). The main causes of
      corneal graft failure were irreversible allograft reaction, endothelial failure,
      and graft infection, which were all seen in higher percentage in the regraft
      group. A best-corrected visual acuity of 20/100 or better was achieved in 377
      eyes (57.8%) in Group I and 11 eyes (20.7%) in Group II (p=0.000). CONCLUSIONS:
      The complications of repeated surgery may reduce final graft clarity and visual
      acuity; the disease process necessitating regrafting may carry a poorer prognosis
      for sight.

PMID- 19396780
TI  - Corneal endothelium in patients with diabetes mellitus: a historical cohort
      study.
AB  - PURPOSE: Retinopathy is the major cause of ocular morbidity in patients with
      diabetes mellitus. Chronic hyperglycemia spares no organ and can affect the
      morphology and function of the various corneal layers, compromising its
      transparency. This study was conducted to associate the status of corneal
      endothelium to diabetes mellitus (DM) and identify risk factors of compromised
      corneal endothelium. METHODS: A total of 220 eyes of randomly selected patients
      (110 diabetic and 110 nondiabetic) were subjected to detailed slitlamp and fundus
      evaluation. Corneal endothelial status was evaluated using the Nidek Confoscan 2.
      Cell density, percentage polymegathism, and pleomorphism were calculated. The
      findings in diabetic patients were compared to those without disease. The outcome
      was correlated to diabetic retinopathy (DR). The effects of hypertension,
      hyperlipidemia, age, gender, type, duration, glycemic control, and grades of DR
      was also considered. RESULTS: The mean corneal endothelial cell density was -175
      cells/mm2 (95% CI -317 to -33 cells/mm2) less in eyes of diabetic patients. The
      number of endothelial cells with polymegathism was significantly greater among
      eyes of diabetic patients. There were less corneal endothelial cells with
      pleomorphism in nondiabetic patients. Polymegathism and pleomorphism of corneal
      endothelial cells seems to be positively associated with DM type II. Cell density
      was significantly lower in eyes with DR than those without DR. CONCLUSIONS:
      Corneal endothelium in diabetic patients seems to be compromised. Evaluation of
      corneal endothelium should be part of protocol for eye care of diabetic patients.

PMID- 19396781
TI  - The relationship between patient age and astigmatism magnitude after congenital
      cataract surgery.
AB  - PURPOSE: To evaluate the magnitude of refractive astigmatism after congenital
      cataract surgery and to define its correlation with patient age. METHODS: The
      authors retrospectively reviewed the charts of all pediatric patients who
      underwent congenital cataract extraction with intraocular lens (IOL) implantation
      through a 3.0-mm clear corneal incision from 1998 to 2003, and had no suture
      removal for 5 months afterward. Thirty-four children were included, aged 2 months
      to 15 years. Refractive astigmatism was assessed manually 1 week, 3 months, and 5
      months after surgery by an experienced optometrist. The paired t test was used to
      compare the magnitude of postoperative astigmatism at different postoperative
      periods. Spearman correlation was used to determine the correlation between
      patient age and the postoperative refractive astigmatism. RESULTS: Mean
      refractive astigmatism in all patients was 1.8+/-1.5 diopters (D) at 1 week
      postoperatively. It significantly decreased to 1.0+/-0.7 D at 3 months
      postoperatively (p=0.001), and to 0.8+/-0.7 D at 5 months postoperatively
      (p=0.03). The change in astigmatism was significantly greater during the first 3
      postoperative months than during the following 2 months (p=0.04). Patient age was
      significantly correlated with 1 week postoperative astigmatism (Spearman
      coefficient, r = -0.46; p=0.006) and with 3 months postoperative astigmatism
      (Spearman coefficient, r =-0.37; p=0.03). CONCLUSIONS: Congenital cataract
      surgery using a small, clear corneal incision for IOL implantation caused high
      early postoperative astigmatism, which spontaneously regressed thereafter.
      Younger patients had higher early postoperative astigmatism.

PMID- 19396782
TI  - The ReZoom multifocal intraocular lens: 2-year follow-up.
AB  - PURPOSE: To evaluate distance, intermediate, and near visual acuity and patient
      satisfaction over a period of 2 years after implantation of the ReZoom multifocal
      intraocular lens. METHODS: Fifty-five eyes of 35 cataract patients were included
      in this retrospective study. Only patients with a preoperative photopic pupillary
      diameter superior to 3 mm were included. Monocular visual acuities and visual
      symptoms were compared at different time points. RESULTS: Preoperative mean
      distance uncorrected visual acuity (UCVA) was 0.5+/-0.3 LogMAR, uncorrected
      intermediate visual acuity (UCiVA) at 50 cm was 0.6+/-0.3 LogMAR, and near
      uncorrected visual acuity (UNVA) was J7.8+/-0.6. Mean follow-up was 28.1+/-7.2
      months. At 6 months, UCVA improved to 0.05+/-0.09 logMAR (p<0.001), UCiVA to
      0.08+/-0.1 LogMAR (p<0.001), and UNVA to J2.4+/-0.4 (p<0.001). At 24 months, UCVA
      was 0.04+/-0.08 LogMAR, UCiVA was 0.07+/-0.1 LogMAR, and UNVA was J2.3+/-0.7. No
      significant differences were observed between the values at 6 months versus 24
      months. At the 3-month visit, moderate glare and halo were reported by 10% and
      13% of patients, respectively. The occurrence of visual symptoms decreased with
      time, with only 7% and 5% of patients reporting moderate glare and halo at the
      last visit, respectively. CONCLUSIONS: The ReZoom lens provides quality vision at
      all distances. Between 6 and 24 months of follow-up, a further improvement of
      optical disturbances rather than uncorrected visual acuity may be expected.

PMID- 19396783
TI  - Bimanual microincisional phacoemulsification combined with viscocanalostomy plus
      deeper sclerectomy.
AB  - PURPOSE: The aim of the study was to evaluate the safety and effectiveness of a
      new technique, two-site bimanual microincisional cataract surgery combined with
      viscocanalostomy plus deeper sclerectomy (two-site bimanual MICS-VC-DS), in
      patients with cataract and glaucoma. DESIGN: Noncomparative, interventional case
      series. METHODS: From December 2005 to October 2007, a consecutive series of 12
      patients (12 eyes) with uncontrolled primary open angle glaucoma (POAG) and
      cataract have undergone two-site bimanual MICS-VC-DS. Postoperative evaluation
      included visual acuity (VA), intraocular pressure (IOP), average retinal nerve
      fiber layer (RNFL) thickness measurement, and gonioscopic, biomicroscopic, and
      funduscopic examination. Paired-samples t test was used. A p value of <0.05 was
      taken as significant. RESULTS: The mean duration of follow-up was 14.6 months (SD
      5.8). At 9 months, mean IOP was 17.0 (SD 4), the mean IOP reduction was 13.2 mmHg
      (SD 5.86). At 9 months post-surgery, the complete success rate was 75%. Qualified
      success was achieved in 100% of patients. At 9 months, the mean number of
      antiglaucoma medications was 0.58 (SD 1.24) (p<0.05). Visual acuity improved by a
      mean value of 2.8 lines. Average RNFL thickness did not change significantly
      during the follow-up period (p=0.781). CONCLUSIONS: Two-site bimanual MICS-VC-DS
      appears to be an effective and safe procedure with quick visual rehabilitation,
      acceptable mid-term IOP control, and the advantage of having fewer complications.

PMID- 19396785
TI  - Incidence of hyperemia associated with bimatoprost treatment in naive subjects
      and in subjects previously treated with latanoprost.
AB  - PURPOSE: Bimatoprost is a potent hypotensive drug used in the treatment of
      glaucoma or ocular hypertension with lower target intraocular pressure (IOP) than
      latanoprost. Its most disturbing side effect is conjunctival hyperemia. The
      authors compared the extent of conjunctival hyperemia in patients receiving
      bimatoprost as initial therapy with that in patients whose treatment with
      latanoprost was replaced by bimatoprost. METHODS: One group of consecutive
      patients with newly diagnosed bilateral primary open-angle glaucoma (POAG) was
      treated with once daily bimatoprost 0.03% ophthalmic solution as initial therapy.
      Treatment in another group of patients who had been on latanoprost treatment for
      at least 3 months was replaced by bimatoprost 0.03%. Conjunctival hyperemia was
      assessed by a single masked observer using a five-point grading scale. RESULTS:
      The mean +/- SD baseline hyperemia scores were 0.4+/-0.3 and 0.70+/-0.3 for the
      firstline and replacement groups, respectively. Following 3 weeks of treatment,
      the mean posttreatment conjunctival hyperemia scores were 2.3+/-1 and 1.1+/-0.5,
      respectively. IOP of 25.2+/-9.8 mmHg and 18.95+/-2.1 mmHg dropped to 18.79+/-2.13
      mmHg and 18.23+/-1.95 mmHg, respectively, following bimatoprost therapy. The
      differences in baseline levels of hyperemia for each group were not statistically
      significant (p=0.478). Changes in hyperemia scores from baseline were highly
      significant (p<0.001) only in first-line therapy patients (p=0.02 for the
      replacement group). CONCLUSIONS: The above findings suggest that patients already
      on prostaglandin therapy may be less likely to experience an increase in
      conjunctival hyperemia induced by bimatoprost.

PMID- 19396784
TI  - Coexistent primary open-angle glaucoma and cataract: interim analysis of a
      trabecular micro-bypass stent and concurrent cataract surgery.
AB  - PURPOSE: To evaluate the safety and efficacy of the iStent Trabecular Micro
      bypass Stent in patients undergoing concurrent cataract and glaucoma surgery.
      METHODS: Prospective, 24-month, uncontrolled, multicenter, multicountry
      evaluation of 58 patients with uncontrolled primary open-angle glaucoma
      (including pseudoexfoliation and pigmentary) and cataract. Patients underwent
      clear cornea phacoemulsification followed by ab interno gonioscopically guided
      implantation of the iStent. Of the 48 per protocol population, 42 patients
      completed 12 months of the 24-month study, and their data are included in this
      interim analysis. RESULTS: At baseline, mean (+/-SD) intraocular pressure (IOP)
      was 21.7+/-3.98 mmHg. At 12 months, mean IOP was reduced to 17.4+/-2.99 mmHg, a
      mean IOP reduction of 4.4+/-4.54 mmHg (p<0.001, 18.3%). At baseline, patients
      were taking a mean 1.6+/-0.8 medications. By 12 months, the mean number of
      medications was reduced to 0.4+/-0.62 (p<0.001). Half the patients achieved an
      IOP < or =18 mmHg and were able to discontinue hypotensive medication by the 12
      month visit. The most commonly reported device-related adverse events were the
      appearance of stent lumen obstruction (7 eyes) and stent malposition (6 eyes).
      None of the adverse events were deemed serious. CONCLUSIONS: In patients
      undergoing concurrent cataract and glaucoma surgery, the iStent was safe and
      efficacious for the reduction of IOP and medication therapy.

PMID- 19396786
TI  - Evaluating a new disc staging scale for glaucomatous damage: the ability to
      detect change over time.
AB  - PURPOSE: To assess the ability of Disc Damage Likelihood Scale (DDLS) in
      detecting glaucomatous changes in the optic nerve on sequential optic disc stereo
      photographs as compared with three other different cup/disc grading systems
      (C/D). METHODS: Eighty-three pairs of stereo-photographs with a minimum of 5-year
      follow-up were examined by one group of three observers masked to chronological
      order by using their clinical expertise. Their conclusions were considered gold
      standard. Another group of three glaucoma experts examined the same masked pairs
      to evaluate glaucomatous changes using four different optic nerve grading
      systems: DDLS, vertical, horizontal, and maximal cup/disc. Ratings of these four
      methods in the second group were then compared with the gold standard. RESULTS:
      Baseline and follow-up photographs of 83 eyes were included. Mean follow-up was 6
      years. The sensitivities for detecting glaucomatous nerve changes were 71.4%,
      63.9%, 66.7%, and 47.2% for DDLS, vertical, horizontal, and maximal cup/disc,
      respectively. The specificity for finding nerve change was 70.9%, 51.1%, 40.4%,
      and 48.9%, respectively. The proportion of photographs identified as showing
      glaucomatous changes differed significantly between the DDLS and vertical C/D
      (VCD) (X2=7.900, p=0.005), between the DDLS and horizontal C/D (HCD) (X2=13.89,
      p=0.000), and between DDLS and maximum C/D (MCD) (X2=4.192, p=0.041). The largest
      area (74.4%) under the receiver operator characteristic curve was obtained by
      using the DDLS. CONCLUSIONS: DDLS had higher sensitivity and specificity for
      detecting glaucomatous changes versus the other three C/Ds when considering
      sequential stereo-photographs.

PMID- 19396787
TI  - Quantitative assessment of anterior chamber volume using slit-lamp OCT and
      Pentacam.
AB  - PURPOSE: To quantitatively assess and compare the anterior chamber volume (ACV)
      by different anterior segment imaging techniques. METHODS: Forty healthy eyes of
      40 patients were recruited and three consecutive measurements of ACV were
      determined prospectively utilizing SL-OCT and Pentacam. Statistical significance
      of interdevice differences between measurements was evaluated by unpaired t test
      and Bland-Altman analysis. The repeatability of three consecutive measurements
      was analyzed by repeated measured analysis of variance. RESULTS: Eighty eyes of
      40 patients (18 female, 22 male) with a mean spherical error of -0.55+/-1.4
      diopters were included in the study. Mean ACV were detected as 163.34+/-29.76 mm3
      by Pentacam and 164.14+/-28.44 mm3 by SL-OCT (unpaired t test, p=0.872). Pentacam
      and SL-OCT displayed a high intrasession repeatability (repeated measured
      analysis of variance, p>0.05). ACV values detected by SL-OCT were clinically
      interchangeable with Pentacam. CONCLUSIONS: Noncontact measurements of ACV using
      SL-OCT and Pentacam were easy to handle and demonstrated good repeatability. The
      tested devices were regarded as compatible in measuring ACV.

PMID- 19396788
TI  - Linear regression analysis of the cumulative defect curve by sectors and other
      criteria of glaucomatous visual field progression.
AB  - PURPOSE: To analyze the progression of visual field loss using sector analysis of
      the cumulative defect curve and other procedures. METHODS: Visual fields of 260
      glaucomatous eyes were analyzed over 2.8 years (SD = 1.2) with at least five
      examinations (mean 6.9; SD = 2.0) using Octopus 311 perimeter and TOP strategy.
      The authors applied Threshold Noiseless Trend (TNT) program, which performs local
      filtering of threshold to reduce fluctuation, and analyzed five criteria: 1) a
      score based on significant progression of eight sectors of the cumulative defect
      curve (CD); 2) a score based on the presence of points (PO) with significant
      progression; 3) global progression (GL) of all local deviations; 4) progression
      of mean defect (MD); 5) progression of the square root of loss variance (sLV).
      The authors estimated false diagnoses (FD), randomly reordering examinations of
      each patient. An index of focality of progression (FI) was obtained. RESULTS: sLV
      presented low sensitivity and GL low specificity. CD and PO presented twice the
      sensitivity of MD, often proving earlier indicators. The authors observed
      significant progression of some of the three criteria in 17.5% of the cases when
      MD <6 dB and in 20.7% when MD >6 dB (FD=5.7%). Agreement between two criteria
      occurred in 6.8% of cases with MD <6 dB and in 11.6% when MD >6 dB (FD=1.9%).
      Result reproducibility in successive examinations was observed in 9.9% of cases
      (FD=1.3%). Focality of progression increased with MD. CONCLUSIONS: PO and CD
      indicate suspected progression earlier than MD. Reproduction of results in
      successive examinations or agreement between criteria allows confirmation of
      progression.

PMID- 19396789
TI  - Effects of astigmatism on the Humphrey Matrix perimeter.
AB  - PURPOSE: To evaluate the influence of astigmatism in terms of its amount and
      direction on the results of Humphrey Matrix perimetry. METHODS: A total of 31
      healthy volunteers from hospital staff were consecutively recruited to undergo
      repeat testing with Humphrey Matrix 24-2 full threshold program with various
      induced simple myopic astigmatism. All subjects had previous experience (at least
      twice) with Matrix testing. To produce simple myopic astigmatism, a 0 diopter
      (D), +1 D, or +2 D cylindrical lens was added and inserted in the 180 degrees
      direction and in the 90 degrees direction after complete correction of distance
      vision. The influences of astigmatism were evaluated in terms of the mean
      deviation (MD), pattern standard deviation (PSD), and test duration (TD).
      RESULTS: A significant difference was observed only in the MD from five sessions.
      The MD in cases of 2 D inverse astigmatism was significantly lower than that in
      the absence of astigmatism. CONCLUSIONS: In patients with inverse myopic
      astigmatism of > or =2 D, the influences of astigmatism on the visual field
      should be taken into consideration when the results of Humphrey Matrix perimetry
      are evaluated.

PMID- 19396790
TI  - Selective laser trabeculoplasty versus argon laser trabeculoplasty in patients
      with uncontrolled open-angle glaucoma.
AB  - PURPOSE: To compare the efficacy of selective laser trabeculoplasty (SLT) to
      argon laser trabeculoplasty (ALT) as treatment and retreatment to lower
      intraocular pressure (IOP) in patients with uncontrolled open-angle glaucoma
      (OAG) on maximally tolerated medication therapy with a follow-up of 12 months.
      METHODS: A total of 120 eyes of 120 patients with uncontrolled OAG were enrolled
      in the study. Group A included patients with IOP >22 mmHg on maximal medical
      therapy. A total of 43 eyes underwent SLT treatment and 41 eyes underwent ALT
      treatment. At the end of the follow-up IOP was <18 mmHg. Group B included
      patients with IOP >20 mmHg at 3 months follow-up after SLT or ALT treatment.
      These patients were retreated randomly, 18 with SLT and 18 with ALT. RESULTS: In
      Group A at the end of the follow-up there was no statistically significant
      difference in IOP lowering between SLT (6.01 mmHg) and ALT (6.12) (p=0.794). In
      Group B at the end of the follow-up patients undergoing SLT presented IOP
      lowering statistically significant to ALT treatment (6.24 mmHg and 4.65 mmHg,
      respectively, p<0.01). DISCUSSION: SLT is effective as treatment for patients
      with OAG and appears to be equivalent to ALT in IOP lowering at 12 months only in
      patients without a prior treatment. In case of retreatment SLT appears to be
      better than ALT in IOP lowering.

PMID- 19396791
TI  - The effect of different doses of intracameral bevacizumab on surgical outcomes of
      trabeculectomy for neovascular glaucoma.
AB  - PURPOSE: To prospectively evaluate the effect of 1.25 mg and 2.5 mg intracameral
      bevacizumab on surgical outcomes of trabeculectomy for neovascular glaucoma
      (NVG), with primary outcome measures being the regression of neovascularization
      of iris (NVI) and reduction of intraocular pressure (IOP). METHODS: Consecutive
      patients with neovascular glaucoma from December 2006 to March 2007 were
      randomized into two cohorts assigned to receive 1.25 mg (Group 1) or 2.5 mg
      (Group 2) intracameral bevacizumab prior to undergoing mitomycin C (MMC)
      trabeculectomy. Surgical outcome measures were evaluated following initial
      injection and during follow-up post-surgery. RESULTS: The most common causes for
      iris neovascularization were central retinal vein occlusion (47.3%) and
      proliferative diabetic retinopathy (36.8%). Following intracameral bevacizumab,
      there was a reduction in IOP compared to baseline in both treatment groups (Group
      1, n=9: -10.4+/-4.5 mmHg, p=0.57; Group 2, n=10: -12.1+/-5.5 mmHg, p=0.1). The
      reduction in IOP was not statistically significant between the two groups
      (p=0.55). None of the eyes underwent further retinal ablation post
      trabeculectomy. Reappearance of NVI was seen in three eyes (Group 1, n=2; Group
      2, n=1) after 3 months. There was no statistically significant difference in
      regression of NVI grade between the treatment groups (p=0.1). CONCLUSIONS: The
      efficacy of an intracameral dose of 2.5 mg of bevacizumab prior to trabeculectomy
      for eyes with NVG is not significantly different from a 1.25 mg dose.
      Intracameral bevacizumab followed by trabeculectomy results in good surgical
      outcomes. Longer follow-up would be needed to evaluate differences in recurrence
      rates of iris neovascularization using different dosages.

PMID- 19396792
TI  - Optical coherence tomography for diagnosis of posterior vitreous detachment at
      the macular region.
AB  - PURPOSE: To assess optical coherence tomography (OCT) for diagnosing posterior
      vitreous detachment (PVD) at the macular region compared to kinetic B-scan
      ultrasonography. METHODS: In the present study, the authors prospectively
      investigated the frequency of PVD at the posterior pole utilizing ocular kinetic
      B-mode sonography in 315 eyes of 188 patients (113 female, 75 male; mean age,
      72.8 years; range, 39-94) prior to cataract surgery. In addition, OCT scans of
      the macular region were performed in all subjects for detection of PVD at the
      macula. RESULTS: A total of 130 eyes (41.3%) had no sonographic signs of PVD. In
      this subset of patients in 36 eyes (27.7%), OCT revealed a flat PVD at the
      macular region with the distance between the posterior hyaloid and retinal
      surface being less than 400 microm (mean distance, 234 +/- 112 microm, range, 24
      398). When combining both methods, the diagnosis of PVD at the posterior pole was
      made in 221 of 315 eyes (70.2%). CONCLUSIONS: OCT is a valuable tool for
      detecting PVD at the macular region, particularly in cases with small distances
      between the retinal surface and posterior hyaloid. Proof of attachment of the
      posterior hyaloid can be established only by combining kinetic ultrasonography
      and OCT.

PMID- 19396793
TI  - Efficacy of intravitreal bevacizumab to treat retinal angiomatous proliferation
      stage II and III.
AB  - PURPOSE: To evaluate the efficacy of intravitreal bevacizumab to treat retinal
      angiomatous proliferation (RAP) stages II and III. METHODS: A retrospective,
      interventional, nonrandomized multicentric study was performed. The files,
      optical coherence tomography (OCT) scans, indocyanine green, and fluorescein
      angiograms of patients with RAP stages II and III who had been treated by
      intravitreal bevacizumab were retrospectively examined. Final visual acuity,
      number of injections, and appearance of adverse events were considered as main
      outcome indicators. RESULTS: Twenty-six eyes from 24 patients (9 male and 15
      female) were treated by intravitreal bevacizumab. Fourteen eyes presented RAP
      stage II and 12 eyes presented RAP stage III. Mean age was 76+/-9 and 79+/-6
      years, respectively. Mean initial best-corrected visual acuity (BCVA) was logMAR
      0.60+/-0.24 and 1.13+/-0.37, respectively. Mean BCVA was 0.62+/-0.26 and 1.06+/
      0.37, respectively, at 6 months (p=0.96 and 0.10, respectively, Student t test
      for paired data) and 0.63+/-0.26 and 1.04+/-0.37, respectively, at 12 months
      (p=0.82 and p=0.06, respectively, Student t test for paired data). The average
      number of injections during the first year was 3.4 and 3.2, respectively.
      CONCLUSIONS: Intravitreal bevacizumab may stabilize visual acuity during the
      first year in RAP lesion stage II and III. Visual prognosis seems to be better in
      RAP II lesions.

PMID- 19396794
TI  - Perfluorocarbon liquid vitreous delamination and wide-angle viewing system in the
      management of complicated diabetic retinal detachment.
AB  - PURPOSE: The authors used perfluorocarbon liquid (PFCL) and a wide-angle viewing
      system (WAVS) to evaluate their efficacy on tractional and combined
      tractional/rhegmatogenous retinal detachment (RD) secondary to proliferative
      diabetic retinopathy (PDR). METHODS: In a prospective, noncomparative,
      interventional study, 76 consecutive cases of severe PDR with tractional and
      combined tractional/rhegmatogenous RD were submitted to vitrectomy en bloc
      excision technique using a WAVS and delamination with PFCL between July 1999 and
      December 2003. None of the patients had had previous retinal photocoagulation
      treatment. Preoperative characteristics, intraoperative findings, and procedures
      as well as postoperative results were recorded. Main outcome measures included
      visual acuity (VA) and rates of retinal reattachment and complications. RESULTS:
      After 1 to 4 years of follow-up (mean 34.3 months), the number of patients
      changed from 3 (3.95%) to 11 patients (14.47%) in the > or =20/40 VA range, from
      12 (15.79%) to 7 (9.21%) in the 20/50 to 20/200 group, and from 61 (80.26%) to 58
      (76.31%) in the < or =20/400 group, preoperatively and postoperatively,
      respectively. The mean final VA improved from 1.2 log-MAR before surgery to 0.89
      after vitrectomy (p=0.001). This modified technique resulted in less bleeding
      during surgery, a better identification of intraocular structures, faster retinal
      reattachment, subretinal fluid reabsorption, and easier dissection of
      fibrovascular membranes, among other benefits. CONCLUSIONS: PFCL and WAVS appear
      to reduce intraoperative complication rates in the management of complicated
      cases of tractional and combined tractional/rhegmatogenous RD secondary to PDR.
      Retinal reattachment and functional vision rates improved after this technique.

PMID- 19396795
TI  - Fundus findings in spontaneous subarachnoid hemorrhage and their correlation with
      neurologic characteristics.
AB  - PURPOSE: To determine the incidence of fundus findings in spontaneous
      subarachnoid hemorrhage (SAH) and their correlation with neurologic
      characteristics. METHODS: In a prospective case series, 202 eyes of 101 patients
      with SAH were evaluated from September 2003 to September 2006. The incidence of
      fundus findings was detected and correlated with gender, age, consciousness
      state, Fisher score, site and number of aneurysms, laterality of aneurysms,
      aneurysmal rebleeding, and mortality rate. RESULTS: Fifty (49.5%) patients had
      normal and 51 (50.5%) patients had abnormal funduscopic examination. Of all eyes,
      disc swelling in 85 (42.1%), retinal hemorrhage in 51 (25.2%), subhyaloid
      hemorrhage in 6 (3%), and vitreous hemorrhage in 3 (1.5%) eyes were detected. No
      relation was found between gender, age, Fisher score, number of aneurysms,
      laterality of aneurysms, aneurysmal rebleeding, and mortality rate and fundus
      findings. However, a correlation was observed between consciousness state and
      retinal hemorrhage (p=0.002) and disc swelling (p=0.002), and also between the
      anterior communicating artery location of aneurysm and retinal hemorrhage
      (p=0.017) and any kind of fundus findings (p=0.007). CONCLUSIONS: Fundus findings
      including hemorrhage and disc swelling are common in patients with SAH and are
      related to the consciousness state and anterior communicating artery location of
      aneurysm.

PMID- 19396796
TI  - Early stage ethambutol optic neuropathy: retinal nerve fiber layer and optical
      coherence tomography.
AB  - PURPOSE: To evaluate retinal nerve fiber layer (RNFL) thickness with optical
      coherence tomography (OCT) in early stage ethambutol optic neuropathy. METHODS:
      The RNFL thickness of 20 eyes of 10 patients who developed optic neuropathy after
      taking ethambutol and visited within 6 months after onset were analyzed and
      compared with those of 54 eyes of 29 healthy age-matched controls. The mean age
      was 67.40+/-10.25 years for the patients with toxic optic neuropathy and 66.78+/
      10.60 for the control group (p=0.948). A full ophthalmologic examination
      including RNFL evaluation with fast RNFL thickness (3.4) scanning using a Stratus
      OCT (Carl Zeiss Meditec, Dublin, CA) was performed. RESULTS: RNFL thicknesses
      associated with early ethambutol optic neuropathy were as follows: temporal
      75.35+/-15.77 microm, superior 124.05+/-24.62 microm, nasal 75.15+/-24.23 microm,
      inferior 127.60+/-22.91 mum, and the average was 100.83+/-16.56 microm. There was
      no significant difference between the RNFL thickness of the patients with the
      early stage of ethambutol optic neuropathy and those of the control group. The
      thickness of RNFL was greater in the temporal quadrant than the nasal quadrant,
      although not statistically significant. CONCLUSIONS: RNFL thickness associated
      with ethambutol optic neuropathy during the early stages was no different from
      the controls. Although not statistically significant, the relative thickening of
      temporal RNFL in our patients might represent a mild swelling of the
      papillomacular bundle.

PMID- 19396797
TI  - The prevalence of anisometropia aniso-astigmatism and amblyopia in
      neurofibromatosis type 1.
AB  - PURPOSE: The purpose of this study was to document the prevalence of
      anisometropia, anisoastigmatism, and anisometropic amblyopia in patients with
      neurofibromatosis-1 (NF1) and to compare it with that in age- and sex-matched
      controls. METHODS: Fifty patients with NF1 and 150 age- and sex-matched controls
      were examined in this study. Cycloplegic autorefraction was attempted on all
      patients <16 years old and without cycloplegia on patients >16 years old.
      Anisometropia was defined as absolute interocular difference of spherical
      equivalent more than or equal to 1 D. Aniso-astigmatism was defined as
      interocular difference of refractive astigmatism of more than or equal to 1 D.
      Amblyopia was defined as two-line decrease in Snellen acuity between the two
      eyes. RESULTS: The overall prevalence of anisometropia, aniso-astigmatism, and
      amblyopia in patients with NF1 was 16%, 20%, and 10%, respectively, and they were
      all significantly higher than in the controls. The amblyopia was either moderate
      or severe in nature and all affected patients had significant astigmatism (>2.5
      D) in the amblyopic eye. CONCLUSIONS: NF1 is a risk factor for anisometropia,
      aniso-astigmatism, and aniso-astigmatic amblyopia and screening patients with NF1
      for refractive errors before age 3 will help to detect patients at risk of
      amblyopia and give them proper treatment.

PMID- 19396798
TI  - Dirofilaria repens in the eyelid: case report of subcutaneous manifestation.
AB  - PURPOSE: The authors report a case of eyelid subcutaneous filariasis. METHODS:
      Thorough history, eye examination, surgical intervention, and parasitologic
      analysis. RESULTS: An adult Dirofilaria repens worm was extracted from the right
      upper eyelid in a man living in Italy presenting to our department with lid
      swelling. CONCLUSIONS: Due to increasing migration of populations to Europe, rare
      manifestations of ocular filariasis are becoming more common. Surgery was both
      diagnostic and therapeutic.

PMID- 19396799
TI  - Fungal scleral keratitis and endophthalmitis following pterygium excision.
AB  - PURPOSE: The authors report a case of fungal scleral keratitis and
      endophthalmitis as a complication of pterygium surgery. METHODS: Case
      presentation. RESULTS: A 46-year old woman underwent pterygium excision with
      topical use of intraoperative mitomycin C. By day 21 after excision, scleral
      melting was followed by fungal keratitis. Endophthalmitis ensued, which rapidly
      progressed, despite surgical and medical interventions. The eye was finally
      enucleated to prevent fungaemia. Pathology revealed a highly disorganized eye
      with disruption of scleral collagen in the area of scleral melting. CONCLUSIONS:
      Fungal keratitis and scleral melting are rare but devastating complications of
      pterygium surgery with adjuvant use of mitomycin C.

PMID- 19396800
TI  - Rifabutin corneal deposits in a patient with acquired immunodeficiency syndrome:
      in vivo confocal microscopy investigation.
AB  - PURPOSE: To establish the real localization of rifabutin-related corneal deposits
      in a patient with human immunodeficiency virus (HIV) infection by in vivo HRT II
      confocal microscopy with related clinicopathologic implications. METHODS:
      Observational case report. After Siena University Institutional Review Board
      approval in May 2008 and specific informed consent, a 54-year-old patient with
      HIV infection under rifabutin treatment for acquired immunodeficiency syndrome
      related Mycobacterium avium complex prevention who developed diffuse corneal
      deposits was examined at the Department of Ophthalmology of Siena University. He
      underwent a complete clinical eye examination, biomicroscopy, and digital slit
      lamp photographs, endothelial specular microscopy, ultrasound pachymetry, and
      confocal microscopy by HRT II system. RESULTS: Confocal scans revealed the
      presence of deep stromal and pre descemetic hyperreflective polymorphous
      deposits. In vivo confocal examination excluded the presence of rifabutin-related
      deposits at endothelial level. CONCLUSIONS: Confocal microscopy enables
      establishment of the real localization of rifabutin deposits at deep stromal
      level, providing a better qualitative analysis of all corneal layers compared to
      biomicroscopic examination, with clinical and physiopathologic implications.

PMID- 19396801
TI  - Reactive keratoma of the central corneal epithelium.
AB  - PURPOSE: The authors present a unique corneal tumor. METHODS: A 75-year-old
      gardener presented with a 1-year history of a slowly growing central corneal
      lesion with progressive visual loss. We performed an ophthalmic examination, slit
      lamp photography, high-frequency ultrasonography, and culture with sensitivity
      (followed by therapeutic scrape biopsy). RESULTS: Clinical examination revealed a
      gray-white central corneal tumor without extension to the limbus. No significant
      tumor neovascularization or intraocular inflammation was noted. High frequency
      ultrasound revealed no penetration of the corneal stroma. The tumor was removed
      with a platinum spatula. Histopathology revealed simple hyperkeratosis
      characterized by stratified hyperkeratotic corneal epithelium with metaplastic
      granular layer characteristic of epidermis. Few and focal clusters of passenger
      bacteria were found (as seen in cutaneous leukoplakia). Cultures revealed a few
      Gram-positive cocci and no fungus. A human papilloma virus wide-screen spectrum
      assay (in situ hybridization) was negative. CONCLUSIONS: The authors present a
      benign keratoma of the central corneal epithelium. High frequency ultrasound and
      scrape biopsy histopathologic techniques were used to diagnose and treat this
      keratoleukoma caused by a reactive keratoma as well as improve his vision.

PMID- 19396802
TI  - Retinal pigment epithelial tumor in a young Asian female.
AB  - PURPOSE: To report a case of low-grade adenocarcinoma of the retinal pigment
      epithelium (RPE) in a young Asian woman. METHODS: Interventional case report with
      histopathologic correlation. RESULTS: A 28-year-old Asian woman with a year-long
      history of floaters presented with a dark pigmented lesion in the right eye.
      Partial lamellar sclerouvectomy was performed and histopathology revealed a
      retina pigment epithelial neoplasm consistent with a low-grade adenocarcinoma.
      The patient responded well to the surgery with no complications. CONCLUSIONS:
      Neoplasms of RPE are rare but must be differentiated from choroidal melanoma, as
      they do not tend to metastasize. Local resection can be a good option for
      peripheral RPE tumors.

PMID- 19396804
TI  - Acute reversible Charles Bonnet syndrome precipitated by sudden severe anemia.
AB  - PURPOSE: To report the sudden onset of reversible Charles Bonnet syndrome
      precipitated byacute severe anemia. METHODS: The charts of three patients (Usher
      syndrome, bilateral macular degeneration, and bilateral retinal vein occlusion)
      with acute Charles Bonnet syndrome in the setting of severe anemia were reviewed.
      RESULTS: Anemia resulted from bladder surgery, recto-colitis, and severe urinary
      tract infection. Hemoglobin ranged from 78 to 86 g/L. Decreased visual acuity and
      formed visual hallucinations (giants, flowers, animals) were present in all three
      patients. Rapid reversal of Charles Bonnet syndrome and visual acuity improvement
      followed blood transfusion. CONCLUSIONS: Acute severe anemia can precipitate
      Charles Bonnet syndrome, which may be reversible by blood transfusion.

PMID- 19396803
TI  - Choroidal nonperfusion with significant subretinal exudation after PDT of
      predominantly classic CNV: an OCT and FFA study.
AB  - PURPOSE: Despite the increasing use of antivascular endothelial growth factors
      (anti-VEGF), photodynamic therapy (PDT) with Verteporfin is still considered the
      gold standard treatment of subfoveal and juxtafoveal classic choroidal
      neovascularization (CNV). METHODS: Case report. RESULTS: The authors report a
      case of a 72-year-old man who developed choroidal nonperfusion and significant
      subretinal fluid formation with associated severe visual loss following PDT of
      predominantly classic juxtafoveal CNV. CONCLUSIONS: Although reported separately,
      these two complications have not been previously reported to occur in association
      after PDT treatment of classic CNV and may represent exaggeration of normal
      events occurring after PDT.

PMID- 19396805
TI  - The equivocal role of silicone oil in the treatment of traumatic endophthalmitis.

PMID- 19396808
TI  - A tissue-engineered model of the intestinal lacteal for evaluating lipid
      transport by lymphatics.
AB  - Lacteals are the entry point of all dietary lipids into the circulation, yet
      little is known about the active regulation of lipid uptake by these lymphatic
      vessels, and there lacks in vitro models to study the lacteal-enterocyte
      interface. We describe an in vitro model of the human intestinal microenvironment
      containing differentiated Caco-2 cells and lymphatic endothelial cells (LECs). We
      characterize the model for fatty acid, lipoprotein, albumin, and dextran
      transport, and compare to qualitative uptake of fatty acids into lacteals in
      vivo. We demonstrate relevant morphological features of both cell types and
      strongly polarized transport of fatty acid in the intestinal-to-lymphatic
      direction. We found much higher transport rates of lipid than of dextran or
      albumin across the lymphatic endothelial monolayer, suggesting most lipid
      transport is active and intracellular. This was confirmed with confocal imaging
      of Bodipy, a fluorescent fatty acid, along with transmission electron microscopy.
      Since our model recapitulates crucial aspects of the in vivo lymphatic-enterocyte
      interface, it is useful for studying the biology of lipid transport by lymphatics
      and as a tool for screening drugs and nanoparticles that target intestinal
      lymphatics.

PMID- 19396809
TI  - Structural, thermodynamic, and kinetic properties of Gramicidin analogue GS6
      studied by molecular dynamics simulations and statistical mechanics.
AB  - Gramicidin S (GS) analogues belong to an important class of cyclic peptides,
      characterized by an antiparallel double-stranded beta-sheet structure with Type
      II' beta-turns. Such compounds can be used as model systems to understand the
      folding/unfolding process of beta-hairpins and more in general of beta
      structures. In the present study, we specifically investigate the
      folding/unfolding behavior of the hexameric Gramicidin S analogue GS6 by using
      all-atoms molecular dynamics (MD) simulations at different temperatures, coupled
      to a statistical mechanical model based on the Quasi Gaussian Entropy theory.
      Such an approach permits to describe the structural, thermodynamic, and kinetic
      properties of the peptide and to quantitatively characterize its
      folding/unfolding transitions.

PMID- 19396812
TI  - Conformational analysis of hydroxymatairesinol in aqueous solution with molecular
      dynamics.
AB  - Molecular dynamics simulations were performed on the naturally occuring lignan
      hydroxymatairesinol (HMR) using the GROMACS software. The aim of this study was
      to explore the conformational behavior of HMR in aqueous solution adopting the
      TIP4P model. The topology of HMR was constructed by hand and HMR was modeled with
      the OPLS-AA force field implemented in GROMACS. The five torsional angles in HMR
      were properly analyzed during the simulations. Correlations through certain
      patterns were observed between the angles. The determining property for the
      conformation preferred in aqueous solution was found to be the dipole moment and
      not the lowest energy in gas phase. The solvation effects on HMR was also studied
      by quantum chemical calculations applying the COnductorlike Screening MOdel
      (COSMO), the results of which were compared with results from a previous study
      using the Polarized Continuum Model (PCM). In the present work, COSMO was found
      to give more credible relative energies than PCM.

PMID- 19396813
TI  - Force-field parameters of the Psi and Phi around glycosidic bonds to oxygen and
      sulfur atoms.
AB  - The Psi and Phi torsion angles around glycosidic bonds in a glycoside chain are
      the most important determinants of the conformation of a glycoside chain. We
      determined force-field parameters for Psi and Phi torsion angles around a
      glycosidic bond bridged by a sulfur atom, as well as a bond bridged by an oxygen
      atom as a preparation for the next study, i.e., molecular dynamics free energy
      calculations for protein-sugar and protein-inhibitor complexes. First, we
      extracted the Psi or Phi torsion energy component from a quantum mechanics (QM)
      total energy by subtracting all the molecular mechanics (MM) force-field
      components except for the Psi or Phi torsion angle. The Psi and Phi energy
      components extracted (hereafter called "the remaining energy components") were
      calculated for simple sugar models and plotted as functions of the Psi and Phi
      angles. The remaining energy component curves of Psi and Phi were well
      represented by the torsion force-field functions consisting of four and three
      cosine functions, respectively. To confirm the reliability of the force-field
      parameters and to confirm its compatibility with other force-fields, we
      calculated adiabatic potential curves as functions of Psi and Phi for the model
      glycosides by adopting the Psi and Phi force-field parameters obtained and by
      energetically optimizing other degrees of freedom. The MM potential energy curves
      obtained for Psi and Phi well represented the QM adiabatic curves and also these
      curves' differences with regard to the glycosidic oxygen and sulfur atoms. Our
      Psi and Phi force-fields of glycosidic oxygen gave MM potential energy curves
      that more closely represented the respective QM curves than did those of the
      recently developed GLYCAM force-field.

PMID- 19396814
TI  - Effects of vancomycin, daptomycin, fosfomycin, tigecycline, and ceftriaxone on
      Staphylococcus epidermidis biofilms.
AB  - Infection of medical implanted material is associated with considerable morbidity
      and costs. In the following work, we investigated the effects of vancomycin,
      daptomycin, fosfomycin, tigecycline, and ceftriaxone on biofilms formed by
      Staphylococcus epidermidis isolates causative for implant infection and catheter
      associated bacteremia. Biofilms were studied using the static microtiter plate
      model and incubated with the antibiotics increasing the concentration from 1x to
      128 x the minimal inhibitory concentration (MIC) of the respective isolate
      tested. To quantify the reduction of the biomass, the optical density ratio (ODr)
      of stained biofilms and the number of growing bacteria were determined.
      Incubation of the staphylococcal biofilms with the antibiotics decreased the
      biofilm ODr (at baseline = 1) for ceftriaxone (0.83 +/- 0.48) but minimally only
      for fosfomycin (0.96 +/- 0.64), daptomycin (1.05 +/- 0.59), tigecycline (1.18 +/-
      0.66), and vancomycin (0.98 +/- 0.44) at exceedingly high concentrations of 128 x
      MIC. The significant reduction of the bacterial growth was not achieved for all
      antibiotics, not even at the highest concentrations tested. Using higher doses of
      the antibiotics may be of some value in the treatment of biofilm-associated
      infections, although effects are seen only at clinically unachievable doses.
      However, to eradicate the staphylococcal biofilm, additional measures like
      debridement and/or removal of the implant are needed.

PMID- 19396815
TI  - Upcoming special journal issues.

PMID- 19396816
TI  - Effects of 1 to 3 years' treatment with alendronate on mechanical properties of
      the femoral shaft in a canine model: implications for subtrochanteric femoral
      fracture risk.
AB  - Bisphosphonate (BP) treatment used to prevent bone loss in postmenopausal
      osteoporosis has recently been implicated in an apparent increase in
      subtrochanteric femoral fractures. Previous work showed that BPs can reduce the
      energy to fracture of cancellous bone, but limited data exist on material-level
      mechanical properties of compact bone from the long bones. This study examined
      intrinsic mechanical properties of the femoral diaphysis of a canine model
      treated for 1 or 3 years with alendronate at two different doses. Seventy-two
      dogs were treated orally with 0.2 mg/kg/day alendronate or 1.0 mg/kg/day
      alendronate; a control group was administered saline. Prismatic beam specimens
      were tested in four-point bending under displacement control, and the intrinsic
      mechanical properties were calculated. No significant differences were found
      among groups in any mechanical property at either 1 or 3 years of treatment. We
      conclude that the material properties of the femoral diaphysis are not degraded
      following 1 to 3 years treatment with alendronate, even at high doses. Longer
      periods of treatment have not been studied using clinical doses of alendronate,
      but such studies need to be carried out to confirm a lack of effect of
      alendronate on mechanical properties of cortical bone in the subtrochanteric
      region of the femur.

PMID- 19396817
TI  - Gemcitabine and paclitaxel every 2 weeks in patients with previously untreated
      urothelial carcinoma.
AB  - BACKGROUND: Patients with urothelial carcinoma are not always amenable to
      cisplatin-based chemotherapy. The authors previously reported that they achieved
      a 60% response rate in patients who failed on cisplatin-based combination
      chemotherapy (methotrexate, vinblastine, doxorubicin, and cisplatin) by using a
      convenient outpatient regimen of gemcitabine (G) and paclitaxel (P) every 2
      weeks. A multicenter trial was initiated in 5 Italian centers to evaluate this
      regimen as first-line chemotherapy. METHODS: From January 2003 to April 2005, 54
      patients who had histologically proven, measurable disease (according to Response
      Evaluation Criteria in Solid Tumors) with a World Health Organization (WHO)
      performance status (PS) from 0 to 2, metastatic or inoperable urothelial
      carcinoma, no prior systemic cytotoxic or biologic treatment, a creatinine
      clearance >or=40 mL per minute, and bilirubin <20 micromol/L received G at a dose
      of 2500 mg/m(2) in 30 minutes and P at a dose of 150 mg/m(2) in 3 hours every 2
      weeks. Granulocyte-colony-stimulating factor (G-CSF) was given for 5 to 7 days
      for neutropenia toxicity of grade >or=3 (grading determined according to the
      National Cancer Institute Common Terminology Criteria for Adverse Events v3.0
      guidelines). From 6 to 12 courses were planned. All patients received at least 1
      cycle of therapy and were included in all analyses. RESULTS: The median patient
      age was 67 years (range 34-78 years), and the median WHO PS was 1 (range, 0-2).
      Metastases occurred in the lung in 17 patients (31%), in lymph nodes in 26
      patients (54%), in the bladder in 20 patients (37%), in bone in 8 patients (15%),
      and in the liver in 8 patients (15%). Fifty-nine percent of patients had >1 site
      of disease, and 13% of patients had >or=3 sites of disease. In total, 343 cycles
      were administered. Five patients achieved a complete response, and 15 patients
      achieved a partial response; thus, the overall response rate was 37% in an intent
      to-treat analysis. Hematologic toxicity was predominant but manageable. G-CSF was
      used in only 6% of cycles. The median survival was 13.2 months, and the median
      time to disease progression was 5.8 months. CONCLUSIONS: In a multicenter study,
      G and P was found to be a well-tolerated outpatient regimen. This regimen
      demonstrated promise and may be considered in patients who are unable to receive
      cisplatin.

PMID- 19396818
TI  - EphA2 overexpression is associated with lack of hormone receptor expression and
      poor outcome in endometrial cancer.
AB  - BACKGROUND: EphA2 is a tyrosine kinase receptor in the ephrin family that is
      implicated in oncogenesis and angiogenesis. The objective of the current
      investigation was to study the role of EphA2 in endometrial cancer and its
      relation to steroid hormone receptor expression. METHODS: EphA2, estrogen
      receptor (ER), progesterone receptor (PR), and Ki-67 expression levels were
      evaluated using immunohistochemistry in 139 endometrioid endometrial carcinoma
      (EEC) samples and in 10 benign endometrial samples. Samples were scored by 2
      investigators who were blinded to clinical outcome. The results were correlated
      with clinicopathologic characteristics using univariate and multivariate
      analysis. A P value <.05 was considered statistically significant. RESULTS: High
      expression of EphA2 was detected in 48% of EEC samples versus 10% of benign
      samples. EphA2 overexpression was associated significantly with high disease
      stage (P = .04), high tumor grade (P = .003), increased depth of myometrial
      invasion (P = .05), low ER expression (P = .01), low PR expression (P = .006),
      and high Ki-67 expression (P = .04). Low ER and PR expression levels were
      associated with high tumor grade, positive lymph nodes, high Ki-67 expression,
      and high EphA2 expression. On univariate analysis of all patients, high EphA2
      expression was associated significantly with shorter disease-specific survival
      (DSS) (P < .001). On multivariate analysis, age (P < .001), high disease stage (P
      = .002), and high EphA2 expression (P = .04) were independent predictors of poor
      DSS. CONCLUSIONS: EphA2 overexpression was associated with aggressive phenotypic
      features in EEC and was associated inversely with ER and PR expression. Thus,
      EphA2 may be an important therapeutic target, especially in patients with hormone
      receptor-negative endometrial carcinoma.

PMID- 19396819
TI  - Patterns of care in a population-based sample of soft tissue sarcoma patients in
      the United States.
AB  - BACKGROUND: Soft tissue sarcomas (STS) are relatively uncommon tumors. Data
      regarding the patterns of care of patients with STS and its consistency with
      available guidelines are relatively sparse. The authors conducted a detailed
      analysis of STS patients diagnosed in 2002 and sampled from the Surveillance,
      Epidemiology, and End Results registries. METHODS: The authors sampled 1369
      patients with invasive sarcomas. Hospital records were reabstracted, and treating
      physicians were contacted to verify the therapy provided to each patient.
      RESULTS: The median age of patients was 60 years. There was a slight male
      predominance among the patients with nongynecologic sarcomas. Fifty percent of
      the patients had localized stage sarcoma. Most patients received surgery, but
      negative margins were obtained in only 50% of patients. Complete resection was
      less frequent in patients >or=50 years old. Radiation therapy was used in 53% of
      patients with extremity sarcomas but in only 20% to 30% of the patients with
      sarcomas at other sites. About 27% of all patients received chemotherapy. Tumor
      grade was significantly associated with the use of radiation and chemotherapy.
      Surgical resection, tumor grade, tumor size, use of radiation therapy, and age
      significantly influenced survival. CONCLUSIONS: Patterns of care of STS differ
      based on the site of the tumor. The patterns of care for extremity sarcomas are
      fairly consistent with the available recommendations, but the patterns of care
      for other sites are less consistent. In addition to certain tumor
      characteristics, age of the patient was significantly associated with therapy and
      patient outcome.

PMID- 19396821
TI  - The AJMG SEQUENCE: Decoding news and trends for the medical genetics community.

PMID- 19396822
TI  - Are the oral-facial-digital syndromes ciliopathies?
AB  - The first oral-facial-digital syndrome was described in 1941 by Mohr, followed by
      a report by Papillon-Leage and Psaume [Papillon-Leage and Psaume (1954); Rev
      Stomatol (Paris) 55:209-227]. Ironically, these became known as oral-facial
      digital syndrome (OFDS) II and I, respectively. Since then, numerous other
      examples of OFDS have been published, and current classification systems include
      up to 13 different types of OFDS. Other than for OFDS I, the causative gene
      defects for these conditions are unknown. Recently however the finding that
      primary ciliary defects can cause multiple anomaly syndromes that phenotypically
      overlap with the OFDS suggests that many, if not all of the OFDS could be caused
      by mutations in ciliary proteins. This review presents the evidence for
      suggesting that the search for causative genes should focus on those that are
      related to ciliary structure and function.

PMID- 19396823
TI  - Arena syndrome is caused by a missense mutation in PLP1.

PMID- 19396824
TI  - A CDKL5 mutated child with precocious puberty.
AB  - To date, 43 patients have been described with mutations in or involving the CDKL5
      gene. The typical phenotype includes early-onset, often intractable epileptic
      seizures and severe mental retardation with very limited progress in psychomotor
      development. Most patients also show impaired social interaction with avoidance
      of eye-to-eye contact, and some clinical features reminiscent of Rett syndrome
      (RTT), including stereotypic hand movements, lack of purposeful hand use,
      acquired microcephaly, and generalized hypotonia. We report on the case of a 5
      year-old girl with a de novo CDKL5 gene mutation who developed early puberty,
      which has not been described before.

PMID- 19396825
TI  - Homozygous female Becker muscular dystrophy.
AB  - We report, for the first time, on a female Becker muscular dystrophy (BMD)
      patient with homozygous dystrophin deletion. The 14-year-old patient, product of
      consanguineous parents, presented with a 7-year history of exercise intolerance
      and recurrent myoglobinuria. Although CK was elevated to 1,800 U/L, no muscle
      weakness, atrophy, or hypertrophy was seen on examination. Muscle pathology
      demonstrated a minimal dystrophic change and faint dystrophin staining pattern.
      Semi-quantitative PCR of dystrophin revealed a homozygous dystrophin deletion of
      exons 45-55, which is predicted to remove 593 amino acids without frame shifting.
      Western blot analysis of skeletal muscle for dystrophin showed a 306 kDa band;
      thus, we made a diagnosis of female BMD. We confirmed identical deletion in both
      father and mother, in hemizygous and heterozygous modes, respectively. Neither
      female Duchenne muscular dystrophy (DMD) nor BMD due to homozygous dystrophin
      mutation has ever been identified although female DMD has been found in patients
      with Turner syndrome or unilateral parental disomy for X chromosome. Our results
      indicate that dystrophinopathy can also be caused in females by homozygosity,
      albeit rare.

PMID- 19396826
TI  - Mucopolysaccharidosis type I in 21 Czech and Slovak patients: mutation analysis
      suggests a functional importance of C-terminus of the IDUA protein.
AB  - Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage
      disorder that is caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA).
      Of the 21 Czech and Slovak patients who have been diagnosed with MPS I in the
      last 30 years, 16 have a severe clinical presentation (Hurler syndrome), 2 less
      severe manifestations (Scheie syndrome), and 3 an intermediate severity
      (Hurler/Scheie phenotype). Mutation analysis was performed in 20 MPS I patients
      and 39 mutant alleles were identified. There was a high prevalence of the null
      mutations p.W402X (12 alleles) and p.Q70X (7 alleles) in this cohort. Four of the
      13 different mutations were novel: p.V620F (3 alleles), p.W626X (1 allele),
      c.1727 + 2T > G (1 allele) and c.1918_1927del (2 alleles). The pathogenicity of
      the novel mutations was verified by transient expression studies in Chinese
      hamster ovary cells. Seven haplotypes were observed in the patient alleles using
      13 intragenic polymorphisms. One of the two haplotypes associated with the
      mutation p.Q70X was not found in any of the controls. Haplotype analysis showed,
      that mutations p.Q70X, p.V620F, and p.D315Y probably have more than one ancestor.
      Missense mutations localized predominantly in the hydrophobic core of the enzyme
      are associated with the severe phenotype, whereas missense mutations localized to
      the surface of the enzyme are usually associated with the attenuated phenotypes.
      Mutations in the 130 C-terminal amino acids lead to clinical manifestations,
      which indicates a functional importance of the C-terminus of the IDUA protein.

PMID- 19396827
TI  - Incidence of the mucopolysaccharidoses in Taiwan, 1984-2004.
AB  - Previous studies on the incidence of the various types of mucopolysaccharidoses
      (MPS) in different populations have shown considerable variation. However,
      information regarding the incidence of MPS in the Asian population is lacking. An
      epidemiological study of the MPS disorders in Taiwan using multiple ascertainment
      sources was undertaken, and incidences of different types of MPS during the
      period of 1984-2004 were estimated. We compared our data with previous reports in
      different populations. The combined birth incidence for all MPS cases was 2.04
      per 100,000 live births. MPS II (Hunter syndrome) had the highest calculated
      birth incidence of 1.07 per 100,000 live births (2.05 per 100,000 male live
      births), comprising 52% of all MPS cases diagnosed. The birth incidences of MPS I
      (Hurler syndrome), III (Sanfilippo syndrome), IV (Morquio syndrome), and VI
      (Maroteaux-Lamy syndrome) were 0.11, 0.39, 0.33, and 0.14 per 100,000 live
      births, respectively, which accounted for 6%, 19%, 16%, and 7% of all MPS,
      respectively. No cases of MPS III D (Sanfilippo syndrome type D), MPS IV B
      (Morquio syndrome type B), MPS VII (Sly syndrome) or MPS IX were ascertained
      during the study period. Overall incidence of MPS in Taiwan was consistent with
      that reported in Western populations. However, in contrast to the higher
      incidence of MPS I in most Western populations, this study showed a higher
      incidence of MPS II in Taiwan. It remains to be investigated whether this
      discrepancy is attributed to the under-diagnosis of MPS I in Taiwan or to ethnic
      differences.

PMID- 19396828
TI  - Array CGH ends diagnostic odyssey for infant with features of Williams and
      Alagille syndrome.

PMID- 19396829
TI  - A novel Alu-mediated Xq28 microdeletion ablates TAZ and partially deletes DNL1L
      in a patient with Barth syndrome.

PMID- 19396830
TI  - 9q Subtelomeric deletion syndrome with diaphragmatic hernia.

PMID- 19396831
TI  - Further clinical delineation of Fine-Lubinsky syndrome.

PMID- 19396832
TI  - Bilateral lambdoid and sagittal synostosis (BLSS): a unique craniosynostosis
      syndrome or predictable craniofacial phenotype?
AB  - Multisutural craniosynostosis that includes bilateral lambdoid and sagittal
      synostosis (BLSS) results in a very characteristic head shape with frontal
      bossing, turribrachycephaly, biparietal narrowing, occipital concavity, and
      inferior displacement of the ears. This entity has been reported both in the
      genetics literature as craniofacial dyssynostosis and in the surgical literature
      as "Mercedes Benz" syndrome. Craniofacial dyssynostosis was first described in
      1976 by Dr. Neuhauser when he presented a series of seven patients with
      synostosis of the sagittal and lambdoid sutures, short stature, and developmental
      delay. Over the past 30 years nine additional patients with craniofacial
      dyssynostosis have been reported in the literature adding to the growing evidence
      for a distinct craniosynostosis syndrome. The term "Mercedes Benz" syndrome was
      coined by Moore et al. in 1998 due to the characteristic appearance of the fused
      sutures on three-dimensional CT imaging. In contrast to the aforementioned
      reported cases of craniofacial dyssynostosis, all three patients had normal
      development. Recently, there have been several case reports of patients with BLSS
      and distinct chromosomal anomalies. These findings suggest that BLSS is a
      heterogeneous disorder perhaps with syndromic, chromosomal, and isolated forms.
      In this manuscript we will present the largest series of patients with BLSS and
      review clinical, CT, and molecular findings.

PMID- 19396833
TI  - Investigation of the candidate region for trigonocephaly in a patient with
      monosomy 9p syndrome using array-CGH.

PMID- 19396834
TI  - Late-onset Lennox-Gastaut syndrome in a patient with 15q11.2-q13.1 duplication.
AB  - The 4 Mb 15q11-q13 region is prone to structural rearrangements. Deletions have
      been identified among the leading causes for genetic diseases such as the Prader
      Willi and Angelman syndromes, while duplications, occurring preferentially on the
      maternal chromosome, produce a typical phenotype that includes mental
      retardation, language delay, seizures and autism. Although a number of such
      patients have been reported, however, there is a paucity of information about
      their clinical outcomes in adult age. We report on a 33-year-old female with a
      microduplication of 15q11-q13 detected by array-CGH analysis, with particular
      reference to the epilepsy phenotype, characterized as a late-onset Lennox-Gastaut
      syndrome.

PMID- 19396835
TI  - Craniosynostosis in patients with Noonan syndrome caused by germline KRAS
      mutations.
AB  - Craniosynostosis, the premature fusion of one or more cranial sutures, is a
      developmental defect that disrupts the cranial morphogenetic program, leading to
      variable dysmorphic craniofacial features and associated functional
      abnormalities. Craniosynostosis is frequently observed as an associated feature
      in a number of clinically and genetically heterogeneous syndromic conditions,
      including a group of disorders caused by activating mutations in genes coding for
      the fibroblast growth factor receptor family members FGFR1, FGFR2, and FGFR3. In
      these disorders, dysregulation of intracellular signaling promoted by the
      aberrant FGFR function is mediated, at least in part, by the RAS-MAPK
      transduction pathway. Mutations in KRAS, HRAS, and other genes coding for
      proteins participating in this signaling cascade have recently been identified as
      underlying Noonan syndrome (NS) and related disorders. While cardinal features of
      these syndromes include distinctive dysmorphic facial features, reduced growth,
      congenital heart defects, and variable ectodermal anomalies and cognitive
      impairment, craniosynostosis is not a recognized feature. Here, we report on the
      occurrence of premature closure of cranial sutures in subjects with NS, and their
      specific association with mutations in the KRAS gene. These findings highlight
      the pathogenetic significance of aberrant signaling mediated by the RAS signaling
      pathway in other known forms of craniosynostosis, and suggest that, even in the
      absence of radiologically demonstrable synostosis of the calvarian sutures,
      dysregulated growth and/or suture closure at specific craniofacial sites might
      contribute to the craniofacial anomalies occurring in NS.

PMID- 19396836
TI  - Possible new syndrome: Left ventricular noncompaction, partial agenesis of the
      corpus callosum, and developmental delay in a Brazilian child.
AB  - We report on the clinical, neuropsychological and language characteristics of a
      boy with left ventricular noncompaction cardiomyopathy (LVNC), agenesis of the
      splenium of the corpus callosum, minor anomalies of face and limbs, mild mental
      retardation, and speech and language disabilities. The occurrence of
      pilomatricoma (calcifying epithelioma) may be part of the clinical spectrum or a
      fortuitous finding. Compared to other related conditions with LVNC suggests that
      this is a "new" unique pattern MCA/MR syndrome.

PMID- 19396837
TI  - Evaluation of prenatal-onset osteochondrodysplasias by ultrasonography: a
      persistent challenge 18 years later.

PMID- 19396838
TI  - Health care supervision for twin pairs.
AB  - Twins are at increased risk for congenital anomalies and have particular health
      care needs, but twin management guidelines do not exist. This review attempts to
      integrate the latest research findings and evidence-based medicine on twins into
      basic clinical recommendations for general pediatricians.

PMID- 19396839
TI  - Fukutin gene mutations in an Italian patient with early onset muscular dystrophy
      but no central nervous system involvement.
AB  - Hypoglycosylation of alpha-dystroglycan characterizes a subgroup of muscular
      dystrophies of variable severity, including Fukuyama congenital muscular
      dystrophy. We found fukutin gene mutations in a 4.5-year-old Italian patient,
      with reduced alpha-dystroglycan expression, dystrophic features on muscle biopsy,
      hypotonia since birth, mild myopathy, but no brain involvement. Mutations in the
      fukutin gene can be associated with much milder phenotypes than classical
      Fukuyama congenital muscular dystrophy, and, although rare, can occur in non
      Japanese.

PMID- 19396840
TI  - Inhibitory effect of paeoniflorin on the inflammatory vicious cycle between
      adipocytes and macrophages.
AB  - Obesity is associated with a state of chronic, low-grade inflammation. It is
      considered that the paracrine loop involving free fatty acid (FFA) and tumor
      necrosis factor (TNF)alpha between adipocytes and macrophages establishes an
      inflammatory vicious cycle that augments the inflammatory changes and insulin
      resistance in obese adipose tissue. Paeoniflorin (PF), one of the major
      components of Paeony root, has been shown to have anti-inflammatory effects in
      vivo. We investigated the effect of PF on the production of FFA and TNFalpha in
      the interaction between adipocytes and macrophages. Coculture of 3T3-L1
      adipocytes and RAW 264.7 macrophages markedly enhanced the production of TNFalpha
      and FFA compared with the control cultures, however, treatment with PF dose
      dependently inhibited the production. We further examined the effects of PF on
      TNFalpha-stimulated adipocyte lipolysis and on FFA-induced macrophage TNFalpha
      expression. PF inhibited TNFalpha-stimulated adipocyte lipolysis in a dose
      dependent manner, which was compatible with suppressed phosphorylation of
      TNFalpha-activated ERK1/2 and preserved downregulation of perilipin. Palmitate,
      one of the most important saturated FFAs, induced macrophage TNFalpha
      upexpression, but PF partially attenuated the effect. These results indicate that
      PF exhibits anti-inflammatory properties by inhibiting the vicious cycle between
      adipocytes and macrophages. PF may be useful for ameliorating the inflammatory
      changes in obese adipose tissue.

PMID- 19396842
TI  - Quantitative cell signalling analysis reveals down-regulation of MAPK pathway
      activation in colorectal cancer.
AB  - Mitogen-activated protein kinases (MAPK) are considered to play significant roles
      in colonic carcinogenesis and kinase inhibitor therapy has been proposed as a
      potential tool in the treatment of this disease. Reverse-phase microarray assays
      using phospho-specific antibodies can directly measure levels of phosphorylated
      protein isoforms. In the current study, samples from 35 cases of untreated
      colorectal cancer colectomies were laser capture-microdissected to isolate
      epithelium and stroma from cancer as well as normal (i.e. uninvolved) mucosa.
      Lysates generated from these four tissue types were spotted onto reverse-phase
      protein microarrays and probed with a panel of antibodies to ERK, p-ERK, p38, p
      p38, p-JNK, MEK and p-MEK. Whereas total protein levels were unchanged, or
      slightly elevated (p38, p = 0.0025) in cancers, activated isoforms, including p
      ERK, p-p38 and p-JNK, were decreased two- to four-fold in cancers compared with
      uninvolved mucosa (p < 0.0023 in all cases except for p-JNK in epithelium, where
      decrement was non-significant). This was backed up by western blotting. Dukes'
      stage B and C cancers displayed lower p-ERK and p-p38 expression than Dukes'
      stage A cancers, although this was not statistically significant. It is concluded
      that MAPK activity may be down-regulated in colorectal cancer and that further
      exploration of inhibitory therapy in this system should be carefully evaluated if
      this finding is confirmed in larger series.

PMID- 19396843
TI  - Activity-structure correlation of Pt/Ru catalysts for the electrodecomposition of
      methanol: the importance of RuO(2) and PtRu alloying.
AB  - Bimetallic catalysts: The effect of PtRu alloying and the influence of RuO(2)
      species on the methanol oxidation activity of PtRu/C catalysts is studied.
      Different heat treatments-utilizing either N(2) or air-are applied to the
      bimetallic materials to enhance the degree of alloying or produce RuO(2)
      [picture: see text]. The catalysts with the best performance are characterized by
      a small particle size, a high degree of PtRu alloying, and the presence of a Pt
      related species on their surface.Herein, we study the effect of both PtRu
      alloying and the presence of RuO(2) species on the promotion of the methanol
      oxidation activity of PtRu/C catalysts. Bimetallic catalysts composed of 15 wt %
      PtRu/Ce(x)C (x=0 or 10) are prepared by using the precipitation-deposition method
      and activated through hydrogen reduction at 470 K. Different heat treatments,
      utilizing either N(2) or air, are applied to the as-prepared catalysts to enhance
      the degree of alloying or produce RuO(2), respectively. The electrocatalytic
      properties, the structure, and the surface composition of the alloys are
      investigated systematically by means of electrochemical measurements coupled with
      X-ray diffraction (XRD) and temperature-programmed reduction (TPR) experiments.
      We find that the N(2) heat treatment improves the catalytic activity of the
      alloys more significantly than the air heat treatment. Also, the current density
      and long-term durability toward methanol oxidation can be significantly enhanced
      by combining a loading of 10 % CeO(2) and N(2) with a heat treatment at 570 K.
      Physical characterization performed by means of TPR reveals that the surface of
      the N(2)-treated sample is covered with Pt, thereby presenting a higher methanol
      oxidation current than the air-treated sample whose surface is composed of RuO(2)
      and some alloy species. Moreover, a model for describing the physical structures
      of the deposited bimetallic crystallites obtained after the N(2) and air
      treatments is proposed. This model suggests that the catalysts with the best
      performance should have a small particle size and exhibit a structure
      characterized by a high degree of PtRu alloying and a Pt-related surface species.
      Therefore, we can conclude that the effect of PtRu alloying on the electro
      oxidation activity of the catalysts is superior to that of the presence of RuO(2)
      species under practical conditions.

PMID- 19396841
TI  - Transgenic expression of n-3 fatty acid desaturase (fat-1) in C57/BL6 mice:
      Effects on glucose homeostasis and body weight.
AB  - The fat-1 gene, derived from Caenorhabditis elegans, encodes for a fatty acid n-3
      desaturase. In order to study the potential metabolic benefits of n-3 fatty
      acids, independent of dietary fatty acids, we developed seven lines of fat-1
      transgenic mice (C57/BL6) controlled by the regulatory sequences of the adipocyte
      protein-2 (aP2) gene for adipocyte-specific expression (AP-lines). We were unable
      to obtain homozygous fat-1 transgenic offspring from the two highest expressing
      lines, suggesting that excessive expression of this enzyme may be lethal during
      gestation. Serum fatty acid analysis of fat-1 transgenic mice (AP-3) fed a high n
      6 unsaturated fat (HUSF) diet had an n-6/n-3 fatty acid ratio reduced by 23% (P <
      0.025) and the n-3 fatty acid eicosapentaenoic acid (EPA) concentration increased
      by 61% (P < 0.020). Docosahexaenoic acid (DHA) was increased by 19% (P < 0.015)
      in white adipose tissue. Male AP-3-fat-1 line of mice had improved glucose
      tolerance and reduced body weight with no change in insulin sensitivity when
      challenged with a high-carbohydrate (HC) diet. In contrast, the female AP-3 mice
      had reduced glucose tolerance and no change in insulin sensitivity or body
      weight. These findings indicate that male transgenic fat-1 mice have improved
      glucose tolerance likely due to increased insulin secretion while female fat-1
      mice have reduced glucose tolerance compared to wild-type mice. Finally the
      inability of fat-1 transgenic mice to generate homozygous offspring suggests that
      prolonged exposure to increased concentrations of n-3 fatty acids may be
      detrimental to reproduction.

PMID- 19396844
TI  - Photoinduced nonadiabatic dynamics of 9H-guanine.
AB  - Surface-hopping simulations are used to study the nonradiative relaxation of 9H
      guanine. Two distinct S(1)-->S(0) (pipi*-->gs) decay channels, both of which pass
      through a conical intersection (CI), are found to be responsible for the
      experimentally observed double-decay behavior [schematic diagram: see text].The
      photoinduced nonadiabatic decay dynamics of 9H-guanine is investigated by surface
      hopping calculations at the semiempirical OM2/MRCI level of theory. Following
      excitation, fast internal conversion from the pipi* (L(a)) excited state to the
      ground state is observed within 800 fs. Relaxation proceeds through two distinct
      S(1)-->S(0) pathways. The first channel goes through a conical intersection with
      pronounced out-of-plane displacement of the C2 atom and yields ultrafast decay
      with a time constant of 190 fs. The second channel evolves through a conical
      intersection with strong out-of-plane distortion of the amino group and leads to
      slower decay with a lifetime of 400 fs. These decay mechanisms and the computed
      decay times are consistent with the available experimental evidence and previous
      theoretical studies.

PMID- 19396846
TI  - Light harvesting by a periodic mesoporous organosilica chromophore.
AB  - Light aqueduct: Periodic mesoporous organosilica exhibits strong light absorption
      due to densely packed organic chromophores within the pore walls. Light energy
      absorbed by 125 biphenyl groups in the pore walls is funneled into a single
      coumarin 1 molecule in the mesochannels with almost 100% quantum efficiency, and
      results in significant enhancement of emission from the coumarin 1 dye.

PMID- 19396845
TI  - Total synthesis of (+)-dibromophakellin.
AB  - Two members of a family of pyrrole-imidazole marine alkaloids, (+)
      dibromophakellin and the nonnatural congener (+)-phakellin, were synthesized
      enantioselectively from 4-hydroxy-L-proline. The chiral aminal at C10 was
      constructed efficiently by means of an Overman-type [3,3] sigmatropic
      rearrangement of an enamide (see scheme).

PMID- 19396847
TI  - In situ enamine activation in aqueous salt solutions: highly efficient asymmetric
      organocatalytic Diels-Alder reaction of cyclohexenones with nitroolefins.
AB  - Deep-sea Diels-Alder: The asymmetric organocatalytic Diels-Alder reaction of
      cyclohexenones with aromatic nitroolefins can be carried out in seawater and
      brine. The reaction proceeds by an in situ enamine activation involving a one
      step concerted addition pathway (see scheme).

PMID- 19396848
TI  - In situ formation of diazonium salts from nitro precursors for scanning
      electrochemical microscopy patterning of surfaces.
AB  - Give me a tip: In situ production of diazonium salts from nitro compounds allows
      the use of diazonium chemistry for microelectrochemical patterning of surfaces by
      scanning electrochemical microscopy. The nitro precursor is reduced at the tip to
      the amine, which is diazotized in the interelectrode space as it diffuses (see
      picture). The tip acts as a source of diazonium salts, allowing sample
      derivatization just beneath the tip.

PMID- 19396849
TI  - All kinds of reactivity: recent breakthroughs in metal-catalyzed alkyne
      chemistry.
AB  - Alkynes of reactions: Recent breakthroughs in metal-catalyzed alkyne reactions,
      which expand the synthetic utility of alkynes, have been achieved. These
      approaches broaden the range of alkynes that are accessible by C--N and C--C bond
      forming reactions and demonstrate that the use of bifunctional heterobimetallic
      catalysts can lead to new reactivity and excellent enantioselectivity (see
      scheme).

PMID- 19396850
TI  - Non-hydrolyzable RNA-peptide conjugates: a powerful advance in the synthesis of
      mimics for 3'-peptidyl tRNA termini.
AB  - Translation of specific small peptides on the ribosome can confer resistance to
      macrolide antibiotics. To reveal the molecular details of this and related
      phenomena, stable RNA-peptide conjugates that mimic peptidyl-tRNA would be
      desirable, especially for ribosome structural biology. A flexible solid-phase
      synthesis strategy now allows efficient access to these highly requested
      derivatives without restriction on the RNA and peptide sequences.

PMID- 19396852
TI  - Direct observation of contact ion-pair formation in aqueous solution.

PMID- 19396853
TI  - Extending rectangular metal-organic frameworks to the third dimension: discrete
      organometallic boxes for reversible trapping of halocarbons occurring with
      conservation of the lattice.

PMID- 19396851
TI  - Artificial restriction DNA cutters as new tools for gene manipulation.
AB  - The final cut. Two types of artificial tools (artificial restriction DNA cutter
      and zinc finger nuclease) that cut double-stranded DNA through hydrolysis of
      target phosphodiester linkages, have been recently developed. The chemical
      structures, preparation, properties, and typical applications of these two man
      made tools are reviewed.Two types of artificial tools that cut double-stranded
      DNA through hydrolysis of target phosphodiester linkages have been recently
      developed. One is the chemistry-based artificial restriction DNA cutter (ARCUT)
      that is composed of a Ce(IV)-EDTA complex, which catalyses DNA hydrolysis, and a
      pair of pseudo-complementary peptide nucleic acid fragments for sequence
      recognition. Another type of DNA cutter, zinc finger nuclease (ZFN), is composed
      of the nuclease domain of naturally occurring FokI restriction endonuclease and a
      designed zinc finger DNA-binding domain. For both of these artificial tools, the
      scission site and specificity can be freely chosen according to our needs, so
      that even huge genomic DNA sequences can be selectively cut at the target site.
      In this article, the chemical structures, preparation, properties, and typical
      applications of these two man-made tools are described.

PMID- 19396854
TI  - Oriented monolayer film of Gd2O3:0.05 Eu crystallites: quasi-topotactic
      transformation of the hydroxide film and drastic enhancement of photoluminescence
      properties.
AB  - Caught on film: A semitransparent and intensely luminescent monolayer film of
      oriented Gd(2)O(3):0.05 Eu platelet crystallites is fabricated by annealing the
      precursor hydroxide film (see scheme). The photoluminescence properties of the as
      transformed film are greatly improved over those of the hydroxide film, and are
      much more pronounced than those of the corresponding Gd(2)O(3):0.05 Eu powder.

PMID- 19396855
TI  - Red blood cell transfusion need at diagnosis adversely affects survival in
      primary myelofibrosis-increased serum ferritin or transfusion load does not.
AB  - Serum ferritin level at diagnosis was available in 185 patients with primary
      myelofibrosis (PMF); twenty-two (12%) patients had serum ferritin >1,000 ng/mL
      and 32 (17%) were red blood cell (RBC) transfusion-dependent. As expected, RBC
      transfusion need and increased serum ferritin displayed strong correlation (P <
      0.0001); in addition, the latter but not the former correlated with advanced age
      (P < 0.0001). During median follow-up of 28 months (range 0.5-231), peak serum
      ferritin levels exceeded 1,000 ng/mL in 41 (22%) patients. On multivariable
      analysis that included age as a covariate, RBC transfusion need at diagnosis (P <
      0.0001), but not increased serum ferritin or transfusion load, predicted
      shortened survival. The prognostic relevance of RBC transfusion need was
      independent of the International Prognostic Scoring System and was also
      illustrated for leukemia-free survival (P = 0.003). In PMF, the presence of a
      more severe erythropoietic defect, and not iron overload, has additional adverse
      prognostic value.

PMID- 19396856
TI  - Elevated AF1q expression is a poor prognostic marker for adult acute myeloid
      leukemia patients with normal cytogenetics.
AB  - Nearly half of the patients with newly diagnosed acute myeloid leukemia have
      normal cytogenetics (NC-AML) and are classified as intermediate risk, but their 5
      year overall survival (OS) ranges from 24 to 42%. Therefore, molecular biomarkers
      to identify poor-risk patients are needed. Elevated AF1q expression in the
      absence of specific poor cytogenetics is associated with poor outcomes in
      pediatric patients with AML and adult patients with myelodysplastic syndrome. We
      examined AF1q expression in 290 patients with NC-AML. We found that patients with
      low AF1q (n = 73) expression (AF1q(low)) have better OS (P = 0.026), disease-free
      survival (P = 0.1), and complete remission rate (P = 0.06) when compared with
      patients with high AF1q expression (AF1q(high) n = 217). The patients with
      AF1q(high) had significantly greater incidence of concurrent tyrosine kinase3
      internal tandem duplication. A subgroup of the patients with AF1q(high) who
      received allogeneic stem cell transplantation (SCT) had a significant better
      relapse-free survival when compared with patients who received
      chemotherapy/autologous SCT (P = 0.04). This study suggests that high AF1q
      expression is a poor prognostic marker for adult patients with NC-AML.

PMID- 19396857
TI  - The influence of treatment in specialized centers on survival of patients with
      thalassemia major.

PMID- 19396858
TI  - Evaluation of predicted knee-joint muscle forces during gait using an
      instrumented knee implant.
AB  - Musculoskeletal modeling and optimization theory are often used to determine
      muscle forces in vivo. However, convincing quantitative evaluation of these
      predictions has been limited to date. The present study evaluated model
      predictions of knee muscle forces during walking using in vivo measurements of
      joint contact loading acquired from an instrumented implant. Joint motion, ground
      reaction force, and tibial contact force data were recorded simultaneously from a
      single subject walking at slow, normal, and fast speeds. The body was modeled as
      an 8-segment, 21-degree-of-freedom articulated linkage, actuated by 58 muscles.
      Joint moments obtained from inverse dynamics were decomposed into leg-muscle
      forces by solving an optimization problem that minimized the sum of the squares
      of the muscle activations. The predicted knee muscle forces were input into a 3D
      knee implant contact model to calculate tibial contact forces. Calculated and
      measured tibial contact forces were in good agreement for all three walking
      speeds. The average RMS errors for the medial, lateral, and total contact forces
      over the entire gait cycle and across all trials were 140 +/- 40 N, 115 +/- 32 N,
      and 183 +/- 45 N, respectively. Muscle coordination predicted by the model was
      also consistent with EMG measurements reported for normal walking. The combined
      experimental and modeling approach used in this study provides a quantitative
      framework for evaluating model predictions of muscle forces in human movement.

PMID- 19396859
TI  - Localization of the full-thickness cartilage lesions in medial and lateral
      unicompartmental knee osteoarthritis.
AB  - This study's aim was to determine the patterns of osteoarthritis (OA) in both
      unicompartmental medial and lateral OA of the knee. Forty patients with medial
      and 20 with lateral unicompartmental knee osteoarthritis were studied to
      determine the location of full-thickness cartilage lesions. Intraoperatively, the
      distance between margins of the lesion and reference lines were measured. The
      femoral measurements were transposed onto lateral radiographs to determine the
      relationship between the lesion site and knee flexion angles. Both tibial and
      femoral lesions were significantly (p < 0.01) more posterior in lateral OA than
      medial OA. In medial OA, the lesion center was, on average, at 11 degrees (SD 3
      degrees) of flexion, whereas in lateral OA, it was at 40 degrees (SD 3 degrees).
      The smallest medial femoral lesions were near full extension and, as they
      enlarged, they extended posteriorly. The smallest lateral femoral lesions
      extended from 20 degrees to 60 degrees flexion. As these lesions enlarged, they
      extended both anteriorly and posteriorly. There was a well-defined relationship
      between the site of the lesions and their size, suggesting that they develop and
      progress in a predictable manner. The relationship was different for medial and
      lateral OA, suggesting that different mechanical factors are important in
      initiating the different types of OA. The lesions in medial OA occur in
      extension, perhaps initiated by events occurring at heel strike. The lesions in
      lateral OA begin at flexion angles above those occurring during the single leg
      stance phase of the gait cycle, so activities other than gait are likely to
      induce lateral OA.

PMID- 19396860
TI  - Endothelial cells incubated with platelet-rich plasma express PDGF-B and ICAM-1
      and induce bone marrow stromal cell migration.
AB  - Platelet-rich plasma (PRP) is used to accelerate bone repair through the growth
      factors released by platelets. The purpose of this study was to evaluate if PRP
      induce human umbilical vein endothelial cells (HUVEC) to express mRNA for
      osteogenic growth factors and stimulate the migration of bone marrow stromal cell
      (BMSC). The effects of PRP were compared to those induced by vascular endothelial
      growth factor-A (VEGF-A) or, as a negative control, by platelet poor plasma
      (PPP). After incubation with PRP, but not with PPP, HUVEC showed an increased
      expression of mRNA for platelet derived growth factor-B (PDGF-B), and this effect
      was not inhibited by an anti-VEGF-A antibody. The migration of BMSC was more
      stimulated by HUVEC incubated with PRP than by HUVEC incubated with low serum
      medium or PPP. Besides, PRP increased the expression of intercellular adhesion
      molecule-1 (ICAM-1) and osteoprotegerin, but did not affect the expression either
      of the receptor activator for nuclear factor kappaB ligand (RANKL) or of RANK.
      These findings support the hypothesis that PRP contribute to bone repair by
      favoring the pro-osteogenic function of endothelial cells, including the
      recruitment of osteoblast precursors and the expression of adhesion molecules for
      monocyte/macrophages, while inhibiting their pro-osteolytic properties.

PMID- 19396861
TI  - Quantifying the motion of Kager's fat pad.
AB  - Kager's fat pad is located in Kager's triangle between the Achilles tendon, the
      superior cortex of the calcaneus, and flexor hallucis longus (FHL) muscle and
      tendon. Its biomechanical functions are not yet established, but recent studies
      suggest it performs important biomechanical roles as it is lined by a synovial
      membrane and its retrocalcaneal protruding wedge can be observed moving into the
      bursal space during ankle plantarflexion. Such features have prompted hypotheses
      that the protruding wedge assists in the lubrication of the Achilles tendon
      subtendinous area, distributes stress at the Achilles enthesis, and removes
      debris from within the retrocalcaneal bursa. This study examined the influence of
      FHL activity and Achilles tendon load on the protruding wedge sliding distance,
      using both dynamic ultrasound imaging and surface electromyogram. Intervolunteer
      results showed sliding distance was independent of FHL activity. This study has
      shown the protruding wedge to slide on average 60% further into the
      retrocalcaneal bursa when comparing the Achilles tendon loaded versus unloaded,
      consistently reaching the distal extremity. Sliding distance was dependent on a
      change in the Achilles tendon insertion angle. Our results support a number of
      hypothesized biomechanical functions of the protruding wedge including:
      lubrication of the subtendinous region; reduction of pressure change within the
      Achilles tendon enthesis organ; and removal of debris from within the
      retrocalcaneal bursa.

PMID- 19396862
TI  - Towards a comprehensive model of feather regeneration.
AB  - Understanding of the regeneration of feathers, despite a 140 year tradition of
      study, has remained substantially incomplete. Moreover, accumulated errors and
      mis-statements in the literature have confounded the intrinsic difficulties in
      describing feather regeneration. Lack of allusion to Rudall's (Rudall [1947]
      Biochem Biophys Acta 1:549-562) seminal X-ray diffraction study that revealed two
      distinct keratins, beta- and alpha-, in a mature feather, is one of the several
      examples where lack of citation long inhibited progress in understanding. This
      article reviews and reevaluates the available literature and provides a
      synthetic, comprehensive, morphological model for the regeneration of a
      generalized, adult contour feather. Particular attention is paid to several
      features that have previously been largely ignored. Some of these, such as the
      beta-keratogenic sheath and the alpha-keratogenic, supra-umbilical, pulp caps,
      are missing from mature, functional feathers sensu stricto because they are lost
      through preening, but these structures nevertheless play a critical role in
      development. A new developmental role for a tissue unique to feathers, the
      medullary pith of the rachis and barb rami, and especially its importance in the
      genesis of the superior umbilical region (SUR) that forms the transition from the
      spathe (rachis and vanes) to the calamus, is described. It is postulated that
      feathers form through an intricate interplay between cyto- and
      histodifferentiative processes, determined by patterning signals that emanate
      from the dermal core, and a suite of interacting biomechanical forces. Precisely
      regulated patterns of loss of intercellular adhesivity appear to be the most
      fundamental aspect of feather morphogenesis and regeneration: rather than a
      hierarchically branched structure, it appears more appropriate to conceive of
      feathers as a sheet of mature keratinocytes that is "full of holes.

PMID- 19396863
TI  - A SNP microarray and FISH-based procedure to detect allelic imbalances in
      multiple myeloma: an integrated genomics approach reveals a wide gene dosage
      effect.
AB  - Multiple myeloma (MM) is characterized by marked genomic heterogeneity. Beyond
      structural rearrangements, a relevant role in its biology is represented by
      allelic imbalances leading to significant variations in ploidy status. To
      elucidate better the genomic complexity of MM, we analyzed a panel of 45 patients
      using combined FISH and microarray approaches. We firstly generated genome-wide
      profiles of 41 MMs and four plasma cell leukemias, using a self-developed
      procedure to infer exact local copy numbers (CNs) for each sample. Our analysis
      allowed the identification of a significant fraction of patients showing near
      tetraploidy. Furthermore, a conventional hierarchical clustering analysis showed
      that near-tetraploidy, 1q gain, hyperdiploidy, and recursive deletions at 1p and
      chromosomes 13, 14, and 22 were the main aberrations driving samples grouping.
      Moreover, mapping information was integrated with gene expression profiles of the
      tumor samples. A multiclass analysis of transcriptional profiles characterizing
      the different clusters showed marked gene-dosage effects, particularly concerning
      1q transcripts; this finding was also confirmed by a nonparametric analysis
      between normalized gene expression levels and local CN variations (1027 highly
      significant correlated genes). Finally, we identified several loci in which gene
      expression correlated with the occurrence of loss of heterozygosity. Our results
      provide insights into the composite network linking genome structure and
      transcriptional features in MM.

PMID- 19396864
TI  - CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant
      mesothelioma -A miRNA microarray analysis.
AB  - Malignant mesothelioma (MM) is an aggressive cancer arising from mesothelial
      cells, mainly due to former asbestos exposure. Little is known about the microRNA
      (miRNA) expression of MM. miRNAs are small noncoding RNAs, which play an
      essential role in the regulation of gene expression. This study was carried out
      to analyze the miRNA expression profile of 17 MM samples using miRNA microarray.
      The analysis distinguished the overall miRNA expression profiles of tumor tissue
      and normal mesothelium. Differentially expressed miRNAs were found in tumor
      samples compared with normal sample. Twelve of them, let-7b*, miR-1228*, miR
      195*, miR-30b*, miR-32*, miR-345, miR-483-3p, miR-584, miR-595, miR-615-3p, and
      miR-885-3p, were highly expressed whereas the remaining nine, let-7e*, miR-144*,
      miR-203, miR-340*, miR-34a*, miR-423, miR-582, miR-7-1*, and miR-9, were
      unexpressed or had severely reduced expression levels. Target genes for these
      miRNAs include the most frequently affected genes in MM such as CDKN2A, NF2, JUN,
      HGF, and PDGFA. Many of the miRNAs were located in chromosomal areas known to be
      deleted or gained in MM such as 8q24, 1p36, and 14q32. Furthermore, we could
      identify specific miRNAs for each histopathological subtype of MM. Regarding risk
      factors such as smoking status and asbestos exposure, significantly
      differentially expressed miRNAs were identified in smokers versus nonsmokers (miR
      379, miR-301a, miR-299-3p, miR-455-3p, and miR-127-3p), but not in asbestos
      exposed patients versus nonexposed ones. This could be related to the method of
      assessment of asbestos exposure as asbestos remains to be the main contributor to
      the development of MM.

PMID- 19396865
TI  - Frequent upregulation of MYC in plasma cell leukemia.
AB  - Plasma cell leukemia (PCL) is a rare form of monoclonal gammopathy, which can
      originate de novo or evolve from multiple myeloma (MM) as a terminal leukemic
      phase. Previous cytogenetic studies of PCL have reported the presence of complex
      karyotypes with involvement of multiple unidentified chromosomal regions. We
      report here the analysis of 12 PCL (10 primary and two secondary) by metaphase
      and FISH analysis combined with oligonucleotide array data (244 k, Agilent).
      Interphase-FISH results were compared with those from a series of 861 newly
      diagnosed patients with MM. Cytogenetic analysis was successful on 11 patients,
      all of whom showed clonal chromosomal abnormalities. Compared with MM,
      t(11;14)(q13;q32) (42% versus 15%; P = 0.027) and t(14;16)(q32;q23) (25% versus
      4%; P = 0.010) were more frequent in PCL, although neither the specific partner
      chromosome involved in the IgH translocation nor the ploidy status predicted for
      survival. Chromosomes 1, 8, 13, and 16 showed the highest number of copy number
      alterations with 8q24 being the chromosomal region most frequently involved. In
      eight of 12 patients we found abnormalities (translocations, one amplification,
      small deletions, and duplications) that directly targeted or were very close to
      MYC. Only four of these changes were detected by routine FISH analysis using
      commercial probes with the others exclusively detected by arrays. Quantitative
      reverse transcription polymerase chain reaction demonstrated that these different
      abnormalities were associated with increased levels of MYC mRNA. We conclude that
      MYC dysregulation by complex mechanisms is one of the major molecular events in
      the oncogenesis of PCL.

PMID- 19396867
TI  - Cytogenetic analysis of 101 giant cell tumors of bone: nonrandom patterns of
      telomeric associations and other structural aberrations.
AB  - Giant cell tumor of bone (GCTB) is a benign but locally aggressive tumor with
      metastatic potential. We performed cytogenetic analysis on 101 GCTB from 92
      patients. Karyotypes were obtained from 95 tumors, 47 of which had clonal
      aberrations. The majority of the cytogenetically abnormal GCTB had multiple, up
      to 28 per tumor, clones. Clonal telomeric associations (tas) and other structural
      and numerical changes were found in about 70, 60, and 30%, respectively, of
      clonally abnormal tumors. Forty-seven aberrations were recurrent, of which 35 are
      novel. The vast majority of the recurrent aberrations were tas, confirming the
      important role of telomeric fusions in the development of GCTB. The frequency of
      tas in GCTB cultures increased with passaging, suggesting a selective advantage
      of tas-positive cells in vitro. The termini most frequently involved in tas were
      22p, 13p, 15p, 21p, 14p, 19q, 1q, 12p, 11p, and 20q. The frequency of tas
      (irrespective of their clonality) was significantly higher in tumors carrying
      clonal changes, indicating that tas are precursors of other types of aberrations.
      In line with this assumption, the chromosomes preferentially involved in tas in a
      given tumor were also the ones most often affected by other rearrangements. We
      did not find the previously reported amplicon in 20q11.1, assessed by
      fluorescence in situ hybridization in 10 tumors. Nor did we find any association
      between cytogenetic features and adverse clinical outcome. Thus, local
      recurrences probably depend more on the adequacy of surgical treatment than on
      the intrinsic biology of the tumors.

PMID- 19396866
TI  - Decreased expression of miR-125b and miR-100 in oral cancer cells contributes to
      malignancy.
AB  - Altered microRNA (miRNA) expression profiles have been observed in numerous
      malignancies, including oral squamous cell carcinoma (OSCC). However, their role
      in disease is not entirely clear. Several genetic aberrations are characteristic
      of OSCC, with amplification of chromosomal band 11q13 and loss of distal 11q
      being among the most prevalent. It is not known if the expression levels of
      miRNAs in these regions are altered or whether they play a role in disease. We
      hypothesize that the expression of miRNAs mapping to 11q are altered in OSCC
      because of loss or amplification of chromosomal material, and that this
      contributes to the development and progression of OSCC. We found that miR-125b
      and miR-100 are down-regulated in OSCC tumor and cell lines, and that
      transfecting cells with exogenous miR-125b and miR-100 significantly reduced cell
      proliferation and modified the expression of target and nontarget genes,
      including some that are overexpressed in radioresistant OSCC cells. In
      conclusion, the down-regulation of miR-125b and miR-100 in OSCC appears to play
      an important role in the development and/or progression of disease and may
      contribute to the loss of sensitivity to ionizing radiation.

PMID- 19396868
TI  - The geometry and motion of nematode sperm cells.
AB  - The nematode sperm cell crawls by recycling major sperm protein (MSP) from dimers
      into subfilaments, filaments, and filament complexes, as a result of thermal
      writhing in the presence of hydrophobic patches. Polymerization near leading
      edges of the cell intercolates MSP dimers onto the tips of growing filament
      complexes, forcing them against the cell boundary, and extending the cytoskeleton
      in the direction of motion. Strong adhesive forces attach the cell to the
      substrate in the forward part of the lamellipod, while depolymerization in the
      rearward part of the cell breaks down the cytoskeleton, contracting the
      lamellipod and pulling the cell body forward. The movement of these cells, then,
      is caused by coordinated protrusive, adhesive and contractile forces, spatially
      separated across the lamellipod. This paper considers a phenomenological model
      that tracks discrete elements of the cytoskeleton in curvilinear coordinates. The
      pseudo-two dimensional model primarily considers protrusion and rotation of the
      cell, along with the evolution of the cell boundary. General assumptions are that
      pH levels within the lamellipod regulate protrusion, contraction and adhesion,
      and that growth of the cytoskeleton, over time, is perpendicular to the evolving
      cell boundary. The model follows the growth and contraction of a discrete number
      of MSP fiber complexes, since they appear to be the principle contributors for
      force generation in cell boundary protrusion and contraction, and the backbone
      for the dynamic geometry and motion.

PMID- 19396869
TI  - "Just" in time: gene theory and the biology of the cell surface.
AB  - Ernest Everett Just's critique of gene theory, his emphasis on the importance of
      cell cytoplasm, especially of the cortex in development and heredity, is placed
      within the context of his times, when the views of embryologists, who emphasized
      heredity as process, and those of geneticists who held determinist conceptions of
      the gene, were irreconcilable. Just's emphasis on the cell cortex in heredity and
      morphogenesis was appreciated by few, but was vindicated by studies of cortical
      inheritance and the morphogenetic role of pre-existing cell structure in ciliated
      protists. His essential criticisms of mechanism remain potent today.

PMID- 19396870
TI  - Mammalian Navigators are microtubule plus-end tracking proteins that can
      reorganize the cytoskeleton to induce neurite-like extensions.
AB  - Mammalian microtubule plus-end tracking proteins (+TIPs) specifically associate
      with the ends of growing microtubules. +TIPs are involved in many cellular
      processes, including mitosis, cell migration and neurite extension. Navigators
      are mammalian homologues of the C. elegans unc-53 protein, an ATPase that has
      been linked to the migration and outgrowth of muscles, axons and excretory
      canals. Here we show that all three mammalian Navigators are +TIPs, consistent
      with a previous study on Navigator 1 (NAV1) (Martinez-Lopez et al., Mol Cell
      Neurosci 2005;28:599-612). Overexpression of GFP-tagged Navigators causes
      displacement of CAP_GLY-motif containing +TIPs, such as CLIP-170, from
      microtubule ends, suggesting that the Navigator-binding sites on microtubule ends
      overlap with those of the CAP_GLY-motif proteins. In interphase cells, mammalian
      Navigators also prominently localize to centrosomes, a localization that does not
      depend on an intact microtubule network. Fluorescence recovery after
      photobleaching (FRAP) experiments indicate that NAV1 associates with
      intracellular structures other than microtubules or centrosomes. Expression of
      GFP-tagged Navigators induces the formation of neurite-like extensions in non
      neuronal cells, showing that Navigators can dominantly alter cytoskeletal
      behavior. For NAV1 this function depends on its ATPase activity; it is not
      achieved by a classical type of MT bundling and stabilization. Combined our data
      suggest that Navigators are +TIPs that can reorganize the cytoskeleton to guide
      cell shape changes. Our data are consistent with a role for Navigators in neurite
      outgrowth.

PMID- 19396872
TI  - Temporal rules in vocal exchanges of phees and trills in common marmosets
      (Callithrix jacchus).
AB  - Marmosets exchange two types of calls: phees and trills. We played back phees and
      trills to investigate the temporal rules of vocal exchanges using ten captive
      common marmosets (Callithrix jacchus). The marmosets usually emitted the same
      type of vocalizations just after the stimulus playbacks, and similar regularities
      were observed in the temporal intervals of phees and in trills. They vocalized
      with shorter intervals when they responded with trills rather than phees, and,
      after the first call, they repeatedly vocalized trills with shorter intervals
      than phees. These results suggest that the temporal rules between phees and
      trills are qualitatively similar but quantitatively different. These results
      might be owing to the different distances over which these contact calls are
      used.

PMID- 19396871
TI  - Cobalt-induced oxidant stress in cultured endothelial cells: prevention by
      ascorbate in relation to HIF-1alpha.
AB  - Endothelial cells respond to hypoxia by decreased degradation of hypoxia
      inducible factor 1alpha (HIF-1alpha), accumulation of which leads to increased
      transcription of numerous proteins involved in cell growth and survival. Ascorbic
      acid prevents HIF-1alpha stabilization in many cell types, but the physiologic
      relevance of such effects is uncertain. Given their relevance for angiogenesis,
      endothelial cells in culture were used to evaluate the effects of ascorbate on
      HIF-1alpha expression induced by hypoxia and the hypoxia mimic cobalt. Although
      EA.hy926 cells in culture under oxygenated conditions did not contain ascorbate,
      HIF-1alpha expression was very low, showing that the vitamin is not necessary to
      suppress HIF-1alpha. On the other hand, hypoxia- or cobalt-induced HIF-1alpha
      expression/stabilization was almost completely suppressed by what are likely
      physiologic intracellular ascorbate concentrations. Increased HIF-1alpha
      expression was not associated with significant changes in expression of the
      SVCT2, the major transporter for ascorbate in these cells. Cobalt at
      concentrations sufficient to stabilize HIF-1alpha both oxidized intracellular
      ascorbate and induced an oxidant stress in the cells that was prevented by
      ascorbate. Whereas the interaction of ascorbate and cobalt is complex, the
      presence of physiologic low millimolar concentrations of ascorbate in endothelial
      cells effectively decreases HIF-1alpha expression and protects against cobalt
      induced oxidant stress.

PMID- 19396873
TI  - Interleukin-6 increases intracellular Ca2+ concentration and induces
      catecholamine secretion in rat carotid body glomus cells.
AB  - Although abundant evidence indicates mutual regulation between the immune and the
      central nervous systems, how the immune signals are transmitted to the brain is
      still an unresolved question. In a previous study we found strong expression of
      proinflammatory cytokine receptors, including interleukin (IL)-1 receptor I and
      IL-6 receptor alpha in the rat carotid body (CB), a well-known arterial
      chemoreceptor that senses a variety of chemostimuli in the arterial blood. We
      demonstrated that IL-1 stimulation increases intracellular calcium ([Ca(2+)](i))
      in CB glomus cells, releases ATP, and increases the discharge rate in carotid
      sinus nerve. To explore the effect of IL-6 on CB, here we examine the effect of
      IL-6 on [Ca(2+)](i) and catecholamine (CA) secretion in rat CB glomus cells.
      Calcium imaging showed that extracellular application of IL-6 induced a rise in
      [Ca(2+)](i) in cultured glomus cells. Amperometry showed that local application
      of IL-6 evoked CA release from glomus cells. Furthermore, the CA secretory
      response to IL-6 was blocked by 200 microM Cd(2+), a well-known Ca(2+) channel
      blocker. Our experiments provide further evidence for the responsiveness of the
      CB to proinflammatory cytokines and indicate that the CB might play a role in
      inflammation sensing and transmission of such information to the brain.

PMID- 19396874
TI  - Poststroke subgranular and rostral subventricular zone proliferation in a mouse
      model of neonatal stroke.
AB  - Stroke in the neonatal brain is an understudied cause of neurologic morbidity.
      Recently we have characterized a new immature mouse model of stroke utilizing
      unilateral carotid ligation alone to produce infarcts and acute seizures in
      postnatal day 12 (P12) CD-1 mice. In this study, the amount of poststroke neural
      progenitor proliferation was examined in the subgranular (SGZ) of the dentate
      gyrus and the subventricular zone (SVZ) 7, 14, and 21days after ischemia (DAI). A
      single IP injection (50 mg/kg) of bromodeoxyuridine (BrdU) given 2 hr before
      perfusion fixation labeled newborn cells. Early cell phenotypes were quantified
      by colabeling with GFAP, nestin, and DCX. Control mice revealed an age-dependent
      decrease in neural proliferation, with an approximately 50% drop in BrdU-labeled
      cell counts at P33 compared with P19 both in the SGZ and in the SVZ. Significant
      reduction in the amount of neural proliferation in the ipsilateral injured SGZ of
      ligated mice correlated with both the severity of the stroke-injury and the acute
      seizure scores. Similar correlations were not detected contralaterally.
      Contralateral SGZ neural proliferation was initially lowered at 7 DAI but
      normalized by 21 DAI. In both injured and control brains, approximately 90% of
      newborn SGZ cells colabeled with nestin, approximately 30% colabeled with GFAP,
      and a few colabeled with DCX. In contrast, poststroke SVZ cell proliferation was
      enhanced ipsi- more than contralaterally at 7 DAI. In the SVZ, the enhanced
      neural proliferation normalized to control levels by P33. In conclusion, the
      neural cell proliferation was differentially altered in the SGZ vs. SVZ after
      neonatal stroke.

PMID- 19396875
TI  - Role of P2Y1 receptor in astroglia-to-neuron signaling at dorsal spinal cord.
AB  - Several studies have shown that astrocytes release neurotransmitters into the
      extracellular space that may then activate receptors on nearby neurons. In the
      present study, the actions of adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS)
      activated astrocyte conditioned medium (ADPbetaS-ACM) on cultured dorsal spinal
      cord neurons were evaluated by using confocal laser scanning microscopy and whole
      cell patch-clamp recording. ADPbetaS caused astrocytic glutamate efflux (43
      microM), which in turn induced inward currents in dorsal horn neurons with short
      time in culture. The inward currents were abolished by 2-amino-5
      phosphonlanoicacid (AP-5; NMDAR antagonist) plus 6-cyano-7-nitroquinoxaline-2,3
      dione (CNQX; non-NMDAR antagonist) but were unaffected by MRS2179 (selective
      P2Y(1) receptor antagonist). Furthermore, N6-methyl-2'-deoxyadenosine-3',5'
      bisphosphate (MRS2179) was used to block glutamate release from astrocytes. As a
      result, ADPbetaS-ACM-induced inward currents in neurons were significantly
      blocked. On the other hand, both NMDAR and non-NMDAR were involved in ADPbetaS
      ACM (concentration was diluted to one-tenth)-evoked small [Ca(2+)](i) transients
      in neurons. Under this condition, the values of glutamate concentrations in the
      medium are close to values for extracellular glutamate concentrations under
      physiological conditions. For this reason, it is possible that astrocyte-derived
      glutamate is important for distant neuron under physiological conditions at
      dorsal spinal cord. These observations indicate that astrocytic P2Y(1) receptor
      activation triggered glutamate efflux, which acts on distant neurons to elevate
      calcium levels or acts on nearby neurons to evoke inward current. Finally, our
      results support the conclusion that the astrocytic P2Y(1) receptor plays an
      important role in bidirectional communication between astrocytes and neurons.

PMID- 19396876
TI  - N-methyl-D-aspartate-stimulated ERK1/2 signaling and the transcriptional up
      regulation of plasticity-related genes are developmentally regulated following in
      vitro neuronal maturation.
AB  - The general features of neuroplasticity are developmentally regulated. Although
      it has been hypothesized that the loss of plasticity in mature neurons may be due
      to synaptic saturation and functional reduction of N-methyl-D-aspartate receptors
      (NMDAR), the molecular mechanisms remain largely unknown. We examined the effects
      of NMDAR activation and KCl-mediated membrane depolarization on ERK1/2 signaling
      following in vitro maturation of cultured cortical neurons. Although NMDA
      stimulated a robust increase in intracellular calcium at both DIV (day in vitro)
      3 and 14, the activation of ERK1/2 and cAMP responsive element-binding protein
      (CREB) was impaired at DIV 14. Specifically, the phosphorylation of ERK1/2 was
      stimulated by both NMDA and KCl at DIV 3. However, at DIV 14, NMDA- but not KCl
      stimulated ERK1/2 and CREB phosphorylation was significantly diminished.
      Consistently, the NMDA-induced transcription of ERK/CREB-regulated genes Bdnf
      exon 4, Arc, and zif268 was significantly attenuated at DIV 14. Moreover, in
      comparison with 3 DIV neurons, the phosphorylated-ERK1/2 in 14 DIV neurons
      displayed a tremendous increase following maturation and was more susceptible to
      dephosphorylation. Blocking calcium channels by nifedipine or NMDAR by APV caused
      a more dramatic ERK dephosphorylation in 14 DIV neurons. We further demonstrate
      that the loss of plasticity-related signaling is unrelated to NMDA-induced cell
      death of the 14 DIV neurons. Taken together, these results suggest that the
      attenuation of certain aspects of neuroplasticity following maturation may be due
      to the reduction of NMDAR-mediated gene transcription and a saturation of ERK1/2
      activity.

PMID- 19396877
TI  - Expression of SLURP-1, an endogenous alpha7 nicotinic acetylcholine receptor
      allosteric ligand, in murine bronchial epithelial cells.
AB  - Mammalian secreted lymphocyte antigen-6/urokinase-type plasminogen activator
      receptor-related peptide-1 (SLURP-1) is a positive allosteric ligand for alpha7
      nicotinic acetylcholine (ACh) receptors (alpha7 nAChRs) that potentiates
      responses to ACh and elicits proapoptotic activity in human keratinocytes.
      Mutations in the gene encoding SLURP-1 have been detected in patients with Mal de
      Meleda, a rare autosomal recessive skin disorder characterized by transgressive
      palmoplantar keratoderma. On the basis of these findings, SLURP-1 is postulated
      to be involved in regulating tumor necrosis factor-alpha (TNF-alpha) release from
      keratinocytes and macrophages via alpha7 nAChR-mediated pathways. In the present
      study, we assessed SLURP-1 expression in lung tissue from C57BL/6J mice to
      investigate the functions of SLURP-1 in pulmonary physiology and pathology.
      Immunohistochemical and in situ hybridization analyses revealed expression of
      SLURP-1 protein and mRNA, respectively, exclusively in ciliated bronchial
      epithelial cells. This was supported by Western blotting showing the presence of
      the 9.5-kDa SLURP-1 protein in whole-lung tissue and trachea. In addition, high
      affinity choline transporter (CHT1) was detected in apical regions of bronchial
      epithelial cells and in neurons located in the lamina propria of the bronchus,
      suggesting that bronchial epithelial cells are able to synthesize both SLURP-1
      and ACh. We also observed direct contact between F4/80-positive macrophages and
      bronchial epithelial cells and the presence of invading macrophages in close
      proximity to CHT1-positive nerve elements. Collectively, these results suggest
      that SLURP-1 contributes to the maintenance of bronchial epithelial cell
      homeostasis and to the regulation of TNF-alpha release from macrophages in
      bronchial tissue.

PMID- 19396878
TI  - Adaptations in 5-HT receptor expression and function: implications for treatment
      of cognitive impairment in aging.
AB  - Malfunction of the serotonin system may contribute to memory deficits during
      aging. We evaluated the 5-HT(6) antagonist RO4368554 in two models of learning
      and memory in aged rats. Male rats (18 months) were assigned to two groups of
      equal cognitive performance. After 2 weeks of 5-HT(6) antagonist RO4368554 (5
      mg/kg, i.p.) treatment, rats showed significant improvement in object recognition
      and social discrimination compared with rats given chronic vehicle. Brains from
      these animals were examined for changes in plasticity-associated proteins Ki-67
      and PCNA. No differences were seen between groups in any of these markers. We
      also measured mRNA expression of 5-HT(6), along with 5-HT(1A), 5-HT(1B), and
      tryptophan hydroxylase-2 mRNAs in 4-month-old and 24-month-old F344 rats.
      Decreases in 5-HT(1B) expression were observed in several forebrain regions in
      the old rats. These results demonstrate that 5-HT(6) and 5-HT(1B) receptors are
      potential targets for treatment of age-related memory disorders.

PMID- 19396879
TI  - Effects of temperature elevation on neuronal inhibition in hippocampal neurons of
      immature and mature rats.
AB  - Febrile seizures are the most common seizure type in children, and hyperthermia
      may contribute to seizure generation during fever. We have previously
      demonstrated that hyperthermia suppressed gamma-aminobutyric acid (GABA)-ergic
      synaptic transmission in CA1 neurons of immature rats. However, whether this
      suppression is age-dependent is unknown. Moreover, it is unclear whether
      hyperthermia has differential effects on neuronal inhibition in CA1 pyramidal
      cells (PCs) and dentate gyrus granule cells (GCs). In this study, we investigated
      the effects of hyperthermia on GABA(A) and GABA(B) receptor-mediated inhibitory
      postsynaptic currents (IPSCs) in CA1 and DG neurons from immature (11-17 days
      old) and mature (6-8 weeks old) rats using whole-cell recordings in vitro. In
      immature rats, hyperthermia decreased the peak amplitude of GABA(A) receptor
      mediated IPSCs (GABA(A) IPSCs) in PCs but not in GCs. However, hyperthermia
      decreased the decay time constant of GABA(A) IPSCs to a similar extent in both
      PCs and GCs. In mature rats, hyperthermia decreased the peak amplitude but not
      the decay time constant of GABA(A) IPSCs in both PCs and GCs. Hyperthermia
      decreased charge transfer (area) of the GABA(A) IPSC of PCs more in immature than
      in mature rats. In contrast, hyperthermia decreased the GABA(B) receptor-mediated
      IPSCs to the same degree in immature and mature rats, for either CA1 or DG
      neurons. Because the hippocampus has been found to be involved in hyperthermia
      induced behavioral seizures in immature rats, we suggest that the higher
      sensitivity of CA1 inhibitory synaptic function to hyperthermia in immature
      compared with mature rats might partially explain the higher susceptibility for
      febrile seizures in immature animals.

PMID- 19396880
TI  - Isatin binding proteins in rat brain: in situ imaging, quantitative
      characterization of specific [3H]isatin binding, and proteomic profiling.
AB  - Isatin (indole-2,3-dione) is an endogenous indole that has a distinct and
      discontinuous distribution in the brain and in other mammalian tissues and body
      fluids. Its output is increased under conditions of stress and anxiety. Its
      biological targets remain poorly characterized, although [(3)H]isatin binding
      sites have been demonstrated in various brain structures. In this study, by using
      a real-time beta-imager, [(3)H]isatin radioligand binding analysis, and proteomic
      identification of proteins specifically bound to the affinity sorbent 5
      aminocaproyl-isatin-Sepharose, we have investigated the distribution of
      [(3)H]isatin specific binding sites in the rat brain, characterized their K(d)
      and B(max), and identified some individual brain isatin binding proteins. The
      binding of [(3)H]isatin to rat brain sections was saturable and characterized by
      K(d) values (of 0.2-0.3 microM) consistent with physiological concentrations. The
      highest B(max) was found in the hypothalamus, consistent with a role in stress.
      In most brain regions, the homologous inhibition of [(3)H]isatin binding by
      increasing concentrations of cold isatin demonstrated complex behavior suggesting
      involvement of various binding proteins characterized by different affinity to
      isatin. Affinity chromatography of Triton X-100 lysates of whole-brain
      homogenates on 5-aminocaproyl-isatin-Sepharose followed by subsequent proteomic
      analysis resulted in identification of 25 individual proteins, including
      glyceraldehyde-3-phosphate dehydrogenase, one of few previously reported isatin
      binding proteins, and a group of cytoskeleton-related proteins. These binding
      sites may be related to the known antiproliferative and proapoptotic activities
      of isatin.

PMID- 19396881
TI  - Selective reduction in microglia density and function in the white matter of
      colony-stimulating factor-1-deficient mice.
AB  - It is still debated whether microglia play a beneficial or harmful role in myelin
      disorders such as multiple sclerosis and leukodystrophies as well as in other
      pathological conditions of the central nervous system. The osteopetrotic (op/op)
      mouse has reduced numbers of cells of monocyte lineage as a result of an
      inactivating mutation in the colony stimulating factor-1 gene. To determine
      whether this mutant mouse might be used to study the role of microglia in myelin
      disorders, we quantified the number of microglia in the central nervous system of
      op/op mice and explored their ability to respond to brain injury created by a
      stab wound. Microglial density in the 2-month-old op/op mice was significantly
      decreased in the white matter tracts compared with the -ge matched wild-type
      controls (by 63.6% in the corpus callosum and 86.4% in the spinal dorsal column),
      whereas the decrease was less in the gray matter, cerebral cortex (24.0%). A
      similar decrease was seen at 7 months of age. Morphometric studies of spinal cord
      myelination showed that development of myelin was not affected in op/op mice. In
      response to a stab wound, the increase in the number of microglia/macrophages in
      op/op mice was significantly less pronounced than that in wild-type control.
      These findings demonstrate that this mutant is a valuable model in which to study
      roles of microglia/macrophages in the pathophysiology of myelin disorders.

PMID- 19396882
TI  - Local modulation of the redox state of p-nitrothiophenol self-assembled
      monolayers using the direct mode of scanning electrochemical microscopy.
AB  - Local reduction of the terminating nitro groups of a p-nitrothiophenol self
      assembled monolayer (SAM) under formation of either hydroxylamine or amino groups
      is invoked using the direct mode of scanning electrochemical microscopy (SECM).
      By choosing the appropriate potential and a potential pulse sequence, the
      reduction of the SAM end groups to the desired oxidation state can be achieved,
      locally restricted to the area of the sample surface directly underneath the
      positioned SECM tip. Following the "writing" of redox microstructures within the
      SAM end groups, the local modification of the redox states is visualized
      ("reading") by using the feedback mode of SECM. The current at the Pt tip
      electrode is determined by the electron-transfer rate for reoxidation of the
      redox mediator at the sample surface. Thus, heterogeneities in the SAM surface,
      which are caused by local differences in the redox state of the end groups, are
      distinguishable due to the different electron-transfer rates governed by the
      redox state of the SAM end groups. To further unequivocally prove the successful
      local modification of the redox state of the SAM end groups during the writing
      process, the micropatterned surface is selectively modified with biotin at areas
      with reduced SAM end groups for further complementary binding of an avidin-enzyme
      conjugate. Selective post-functionalization with an avidin-alkaline phosphatase
      conjugate allows visualization of the microstructure using the generator
      collector mode of SECM.

PMID- 19396883
TI  - Mono- and multisite solid catalysts in cascade reactions for chemical process
      intensification.
AB  - Catscade reactions: Heterogeneous catalysis can enable sustainability by carrying
      out multistep reactions in one step. It is shown that single- and multisite solid
      catalysts can be designed to carry out cascade reactions for the synthesis of
      fine chemicals.

PMID- 19396884
TI  - Ruthenium-catalyzed selective monoamination of vicinal diols.
AB  - The monoamination of vicinal diols in the presence of in situ generated ruthenium
      catalysts has been investigated. Among the various phosphines tested in
      combination with [Ru(3)(CO)(12)], N-phenyl-2-(dicyclohexyl-phosphanyl)pyrrole
      showed the best performance. After optimization of the reaction conditions this
      system was applied to different secondary amines and anilines as well as a number
      of vicinal diols. With the exception of ethylene glycol, monoamination of the
      vicinal diols occurred selectively and the corresponding amino alcohols were
      obtained in good yields, producing water as the only side product.

PMID- 19396885
TI  - Synthesis and properties of (triptycenedicarboxylatio)zinc coordination networks.
AB  - (Triptycenedicarboxylato)zinc metal-organic frameworks (MOFs) based on paddle
      wheel secondary building units (SBUs) with different axial ligands have been
      prepared. The reproducible formation of the layered paddle-wheel structures from
      triptycenedicarboxylic acid (H(2)TDC) and zinc nitrate under various conditions
      seems to be characteristic of this acid and is utilized for the construction of
      3D frameworks by a pillaring approach. We attempted to bring additional
      functionalities into MOFs by employing the appropriate pillaring ligands, for
      example, bis(4-pyridyl)-s-tetrazine and bis(4-pyridyl)-dimethoxy-p
      phenylenedivinylene, and investigated certain properties of some MOF materials,
      such as guest-exchange behavior, luminescence, microporosity, and stability.

PMID- 19396886
TI  - Encapsulation and sustained release of curcumin using superparamagnetic silica
      reservoirs.
AB  - For controlled release and targeted delivery of curcumin in an aqueous medium a
      method of encapsulating curcumin and magnetic nanoparticles inside porous silica
      matrix has been developed. Curcumin and superparamagnetic nanoparticles are
      loaded inside porous silica in a single process. The graphic shows the TEM image
      of microtomed sample of Fe(3)O(4) particles surrounded by a silica matrix.

PMID- 19396887
TI  - Adaptation and optical signal generation in a constitutional dynamic network.
AB  - Self-sorting dynamic library: The effector-induced modulation of the shape and
      constitution of the members of a constitutional dynamic network (see scheme)
      allows for the regulation of the interconnected constituents and for the control
      of an emergent function, here the generation of an optical output which
      originates from a charge-transfer interaction.

PMID- 19396888
TI  - Racemization of alcohols catalyzed by [RuCl(CO)2(eta(5)
      pentaphenylcyclopentadienyl)]--mechanistic insights from theoretical modeling.
AB  - Two possible pathways of inner-sphere racemization of sec-alcohols by using the
      [RuCl(CO)(2)(eta(5)-pentaphenylcyclopentadienyl)] catalyst (1) have been
      thoroughly investigated by means of density function calculations. To be able to
      racemize alcohols, catalyst 1 needs to have a free coordination site on the
      metal. This can be achieved either by a eta(5)-->eta(3) ring slippage or by
      dissociation of a carbon monoxide (CO) ligand. The eta(5)-->eta(3) ring-slip
      pathway was found to have a high potential energy barrier, 42 kcal mol(-1), which
      can be explained by steric congestion in the transition state. On the other hand,
      CO dissociation to give a 16-electron complex has a barrier of only 22.6 kcal
      mol(-1). We have computationally discovered a mechanism involving CO
      participation that does not require eta(5)-->eta(3) ring slippage. The key
      features of this mechanism are 1) CO-assisted exchange of chloride for alkoxide,
      2) alcohol-alkoxide exchange, and 3) generation of an active 16-electron complex
      through CO dissociation with subsequent beta-hydride elimination as the
      racemization step. We have found a low-energy pathway for reaction of 1 with
      potassium tert-butoxide and a pathway for fast alkoxide exchange with interaction
      between the incoming/leaving alcohol and one of the two CO ligands. We predict
      that dissociation of a Ru-bound CO ligand does not occur in these exchange
      reactions. Dissociation of one of the two Ru-bound CO ligands has been found
      necessary only at a later stage of the reaction. Though this barrier is still
      quite high, our results indicate that it is not necessary to cross the CO
      dissociation barrier for the racemization of each new alcohol. Thus, the
      dissociation of a CO ligand is interpreted as a rate-limiting reaction step in
      order to create a catalytically active 16-electron complex.

PMID- 19396889
TI  - Chiral cobalt-catalyzed enantiomer-differentiating oxidation of racemic benzoins
      by using molecular oxygen as stoichiometric oxidant.
AB  - An efficient enantioselective oxidative reaction catalyzed by a chiral cobalt
      complex has been developed by using molecular oxygen as the stoichiometric
      oxidant (see scheme). The very mild reaction conditions of the catalytic system
      provide access to a wide range of benzoins (alpha-hydroxyketones) in high yield
      and excellent enantioselectivity (s (k(f)/k(s)) up to 47). This method is very
      versatile because the sole by-product of our oxidation process is water, which
      makes our system more eco-friendly and green.

PMID- 19396890
TI  - Palladium(0)-catalyzed cross-coupling of potassium (Z)-2-chloroalk-1-enyl
      trifluoroborates: a chemo- and stereoselective access to (Z)-chloroolefins and
      trisubstituted alkenes.
AB  - We describe the preparation of a series of new potassium trifluoroborates 1 and
      the study of their behaviour in a Pd(0)-catalyzed cross-coupling reaction. We
      found that compounds 1 are endowed with original properties as they behave as
      nucleophilic cross-coupling partners chemoselectively but also as ambivalent
      synthons. The usefulness of this methodology has been successfully illustrated by
      the first total synthesis of an N-acyl spermidine.

PMID- 19396891
TI  - Direct C-C cross-coupling of secondary and primary alcohols catalyzed by a gamma
      alumina-supported silver subnanocluster.
AB  - Let's drink to that! Two alcohols (one primary and one secondary) can be coupled
      in an atom-efficient process by a hydrogen-autotransfer catalytic system in the
      form of silver subnanoclusters supported on gamma-Al(2)O(3). The recyclable
      heterogeneous catalyst promoted the one-pot C-C cross-coupling in the presence of
      a catalytic amount of the weak base Cs(2)CO(3) (see reaction mechanism).

PMID- 19396894
TI  - Rational design of an organometallic glutathione transferase inhibitor.
AB  - Double trouble: A hybrid organic-inorganic (organometallic) inhibitor was
      designed to target glutathione transferases. The metal center is used to direct
      protein binding, while the organic moiety acts as the active-site inhibitor (see
      picture). The mechanism of inhibition was studied using a range of biophysical
      and biochemical methods.

PMID- 19396895
TI  - Interactive radical dimers in photoconductive organic thin films.
AB  - Fully interactive: Overlap between extended unoccupied molecular orbitals leads
      to the high photoconductivity of interactive radical dimers. Sandwich-type cells
      (see picture; ITO = indium tin oxide) comprising highly oriented thin films of a
      disjoint diradical, 4,4'-bis(1,2,3,5-dithiadiazolyl) (BDTDA) exhibit a
      photocurrent with a high on/off ratio at reverse bias voltages and photovoltaic
      behavior at zero bias voltage.

PMID- 19396893
TI  - The natural products beauveriolide I and III: a new class of beta-amyloid
      lowering compounds.
AB  - Attacking Alzheimer's by ACAT: The aggregation of beta-amyloid peptides,
      especially Abeta(42), into senile plaques is a hallmark of Alzheimer's disease
      (AD). We show that the fungal natural products beauveriolides I and III can
      potently decrease Abeta secretion from cells expressing human amyloid precursor
      protein; this offers a potential new scaffold for the development of compounds
      with proven bioavailability for the treatment of AD.

PMID- 19396897
TI  - Synthesis and optical properties of 2-(benzo[b]thiophene-3-yl)pyrroles and a new
      BODIPY fluorophore (BODIPY = 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene).
AB  - 2-(Benzo[b]thiophene-3-yl)-1-vinylpyrrole has been synthesized directly from 3
      acetylbenzo[b]thiophene oxime and acetylene (flow system, KOH-DMSO, 120 degrees
      C, 5 h) in 68% yield. Devinylation of the synthesized pyrrole (Hg(OAc)(2),
      NaBH(4), 50 degrees C) led to the corresponding 2-(benzo[b]thiophene-3-yl)pyrrole
      in 63% yield. Trifluoroacetylation of both the pyrroles with trifluoroacetic
      anhydride (80 degrees C, 1 h) gave the corresponding 5-trifluoroacetyl pyrroles
      in 97% and 76% yields, respectively. 2-(Benzo[b]thiophene-3-yl)pyrrole was
      reacted subsequently with mesityl aldehyde, 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone (DDQ), and BF(3)OEt(2) to afford 4,4-difluoro-3,5
      di(benzo[b]thiophene-3-yl)-8-mesityl-4-bora-3a,4a-diaza-s-indacene, a
      representative of the novel BODIPY fluorophore family (BODIPY = 4,4-difluoro-4
      bora-3a,4a-diaza-s-indacene), in 34% overall yield. The synthesized pyrroles
      exhibit promising optical properties (absorption and emission spectra, nonlinear
      optical (NLO) features), superior to existing analogues. The BODIPY fluorophore
      displays an intense red-shifted fluorescence emission in CH(2)Cl(2) (625 nm, 0.84
      fluorescence quantum yield) that is fully preserved in the solid state.

PMID- 19396898
TI  - Patterns of expression of Bardet-Biedl syndrome proteins in the mammalian cochlea
      suggest noncentrosomal functions.
AB  - Bardet-Biedl syndrome is a heterogeneous disorder causing a spectrum of symptoms,
      including visual impairment, kidney disease, and hearing impairment. Evidence
      suggests that BBS gene mutations cause defective ciliogenesis and/or cilium
      dysfunction. Cochlear development is affected by BBS gene deletion, and adult
      Bbs6(-/-) and Bbs4(-/-) mice are hearing impaired. This study addresses BBS
      protein expression in the rodent cochlea, to gain a better understanding of its
      function in vivo. As predicted by in vitro studies, Bbs6 immunofluorescence was
      localized to the basal bodies of supporting cells and sensory hair cells prior to
      the onset of hearing. In adult tissue, Bbs6 expression persisted in afferent
      neurons, including within the dendrites that innervate hair cells, implicating
      Bbs6 in a sensory neuronal function. Bbs2, which interacts with Bbs6, was also
      localized to hair cell basal bodies and stereociliary bundles. Additionally, Bbs2
      was expressed in supporting cells at their intercellular boundaries, in a
      spatiotemporal pattern mirroring the development of the microtubule network. Bbs4
      localized to cilia and developing cytoplasmic microtubule arrays. Pcm-1, a
      microtubular protein that interacts with Bbs4 in vitro, showed a comparable
      expression. Depolymerization of microtubules in slice preparations of the living
      cochlea resulted in Bbs4 and Pcm-1 mislocalization. Pcm-1 was also mislocalized
      in Bbs4(-/-) mice. This suggests that Bbs4/Pcm-1 interactions may be important in
      microtubule-dependent cytoplasmic trafficking in vivo. In summary, our findings
      indicate that BBS proteins adopt a range of cellular distributions in vivo, not
      restricted to the centrosome or cilium, and so broaden the possible underlying
      pathomechanisms of the disease.

PMID- 19396902
TI  - [Pharmazie in unserer Zeit 3/2009].

PMID- 19396903
TI  - [Elemental iron and iron oxides in new applications].

PMID- 19396896
TI  - Searching for disease modifiers-PKC activation and HDAC inhibition - a dual drug
      approach to Alzheimer's disease that decreases Abeta production while blocking
      oxidative stress.
AB  - A series of benzolactam compounds were synthesized, some of which caused a
      concentration-dependent increase in sAPPalpha and decrease in Abeta production in
      the concentration range of 0.1-10 microM. Moreover, some compounds showed
      neuroprotective effects in the 10-20 microM range in the HCA cortical neuron
      model of oxidative stress and no toxicity in measurements of neuron viability by
      MTT assay, even at the highest concentrations tested (20 microM). Alzheimer's
      disease (AD) is a well-studied neurodegenerative process characterized by the
      presence of amyloid plaques and neurofibrillary tangles. In this study, a series
      of protein kinase C (PKC) activators were investigated, some of which also
      exhibit histone deacetylase (HDAC) inhibitory activity, under the hypothesis that
      such compounds might provide a new path forward in the discovery of drugs for the
      treatment of AD. The PKC-activating properties of these drugs were expected to
      enhance the alpha-secretase pathway in the processing of amyloid precursor
      protein (APP), while their HDAC inhibition was anticipated to confer
      neuroprotective activity. We found that benzolactams 9 and 11-14 caused a
      concentration-dependent increase in sAPPalpha and decrease in beta-amyloid
      (Abeta) production in the concentration range of 0.1-10 microM, consistent with a
      shift of APP metabolism toward the alpha-secretase-processing pathway. Moreover,
      compounds 9-14 showed neuroprotective effects in the 10-20 microM range in the
      homocysteate (HCA) cortical neuron model of oxidative stress. In parallel, we
      found that the most neuroprotective compounds caused increased levels of histone
      acetylation (H4), thus indicating their likely ability to inhibit HDAC activity.
      As the majority of the compounds studied also show nanomolar binding affinities
      for PKC, we conclude that it is possible to design, de novo, agents that combine
      both PKC-activating properties along with HDAC inhibitory properties. Such agents
      would be capable of modulating amyloid processing while showing neuroprotection.
      These findings may offer a new approach to therapies that exhibit disease
      modifying effects, as opposed to symptomatic relief, in the treatment of AD.

PMID- 19396904
TI  - Tandem multimer expression of angiotensin I-converting enzyme inhibitory peptide
      in Escherichia coli.
AB  - It is common for small tandem peptide multimer genes to be indirectly inserted
      into expression vectors and fused with a protein tag. In this study, a multimer
      of the tandem angiotensin I-converting enzyme inhibitory peptide (ACE-IP) gene
      was directly transferred to a commercially available vector and the designed gene
      was expressed as a repeated peptide in Escherichia coli BL21(DE3)pLysS. The
      process further developed in our study was the construction of six-repeated ACE
      IP synthetic genes and their direct insertion. Protein expression in inclusion
      bodies was confirmed by SDS-PAGE and Western blot. Acid hydrolysis of inclusion
      bodies produced single-unit peptides through cleavage of the aspartyl-prolyl
      bonds. This cleaved recombinant peptide (rACE-IP) was purified using immuno
      affinity chromatography followed by reversed phase-HPLC. 105-115 mg of the
      lyophilized recombinant peptide was obtained from 1 L E. coli culture. In vitro
      biological activity of rACE-IP was indistinguishable from that of the natural
      peptide produced by hydrolysis in artificial gastric juice or by acidic
      hydrolysis. The rACE-IP prepared by recombinant DNA technology and solid-phase
      synthesis methods showed a similar IC(50). This strategy could be used for the
      expression of important peptides, which have N-terminal proline (P) and C
      terminal aspartic acid residues (D) for commercial applications, e.g. functional
      foods and drinks.

PMID- 19396905
TI  - [Physiological significance of iron].

PMID- 19396906
TI  - [Iron oxide - distribution of tablets in the gastrointestinal tract].

PMID- 19396907
TI  - [Iron metabolism disorders].

PMID- 19396908
TI  - [Toadflax--a masked bloom conceals its identity].

PMID- 19396911
TI  - [The current status of gene therapy in severe immunodeficiency].

PMID- 19396912
TI  - [Human antibodies from cattle].

PMID- 19396914
TI  - [Iron deficiency and iron from medical and pharmacy historical perspective].

PMID- 19396915
TI  - [Iron, calcium and magnesium salts].

PMID- 19396916
TI  - [Calcium salts: fantastic and enlightening].

PMID- 19396917
TI  - [Prevention and treatment of osteoporosis].

PMID- 19396918
TI  - [Magnesium compounds].

PMID- 19396919
TI  - [Minerals and trace elements--a case for discussion].

PMID- 19396924
TI  - Introducing mechanistic models in Process Analytical Technology education.

PMID- 19396931
TI  - Intranuclear fluorescence resonance energy transfer analysis of plasmid DNA
      decondensation from nonviral gene carriers.
AB  - BACKGROUND: There has been considerable interest in researching the regulatory
      mechanisms that control transgene expression. In particular, there is impetus to
      investigate the intranuclear mechanisms for gene expression in order to improve
      the transfection efficiency of nonviral gene carriers. METHODS: To clarify the
      direct relationship between DNA decondensation and gene expression, plasmid DNA
      encoding Keima-Red fluorescent protein was doubly-labeled by a pair of donor
      acceptor fluorescent dyes (fluorescein and Cy3), and transfected to HuH-7 cells
      using nonviral gene carriers: polyethylenimine (polyplex) and LipofectAMINE 2000
      (lipoplex). Fluorescence resonance energy transfer analysis between the two dyes
      represents the condensation state of the pDNA. The intranuclear trafficking and
      condensation state of the pDNA were explored in transgene expressing and non
      expressing cells under confocal laser scanning spectromicroscopy. RESULTS: The
      majority of transgene positively expressing cells transfected with polyplex and
      lipoplex had decondensed pixels in the nucleus. The majority of non-expressing
      cells transfected with polyplex had only condensed pixels in the nucleus. The
      majority of non-expressing cells transfected with lipoplex had no pixels in the
      nucleus. CONCLUSIONS: Both polyplex and lipoplex marked a strong correlation
      between pDNA decondensation and transgene expression, yet the major limiting
      factor for transgene expression was different. In polyplex, the pDNA
      decondensation after nuclear entry was the major determining factor for transgene
      expression, whereas the nuclear entry itself was the chief determining step for
      transgene expression by lipoplex. This imaging technique allowed in situ
      observation of pDNA in the nucleus, providing important information about DNA
      behavior for gene expression.

PMID- 19396932
TI  - Osteoinduction by microbubble-enhanced transcutaneous sonoporation of human bone
      morphogenetic protein-2.
AB  - BACKGROUND: Bone morphogenetic protein-2 (BMP-2) is believed to participate in
      bone healing and regeneration. Previous studies using BMP-2 in clinical
      applications have encountered difficulties that include the lack of an efficient,
      safe and simple delivery system, and expensive proteins and matrices. The gene
      transfer approach is a promising option for utilizing BMP-2. Viral vector
      mediated gene transfer is efficient, but safety concerns prevent its clinical
      application for common diseases. Sonoporation is a simple and inexpensive method
      that only requires a plasmid and a sonoporation device. METHODS: We used a
      plasmid-based human BMP-2 construct (pCAGGS-BMP-2) and examined the induction of
      bone in the skeletal muscle of mice after plasmid transfer by transcutaneous
      sonoporation. First, an in vitro study was performed to confirm the expression of
      BMP-2 after gene transfer by sonoporation using pCAGGS-BMP-2. Next, the BMP-2
      gene was transferred into the skeletal muscle of mice by transcutaneous
      sonoporation using pCAGGS-BMP-2. BMP-2 production was assessed via
      immunohistochemistry, and osteoinduction was verified by radiography, histology
      and biochemical assays. RESULTS: The presence of human BMP-2, alkaline
      phosphatase and osteocalcin mRNA and the production of the alkaline phosphatase
      were observed in vitro. Moreover, mature bone was observed in mice sonoporated
      with pCAGGS-BMP-2, confirming that transcutaneous sonoporation with pCAGGS-BMP-2
      caused osteoinduction in the skeletal muscle of mice. CONCLUSIONS: These results
      suggest the possibility of the effective clinical use of human BMP-2 gene therapy
      using transcutaneous sonoporation, and should facilitate clinical applications of
      BMP-2 gene therapy.

PMID- 19396933
TI  - Clarification: pediatric emergency medications and immediate threat to life.

PMID- 19396934
TI  - Praxinor: abuse and dependence.

PMID- 19396935
TI  - Bisphosphonates: atypical fractures?
AB  - A disturbing series of atypical hip fractures in patients receiving long-term
      bisphosphonate therapy was recently published. An unusual radiological pattern of
      cortical thickening was sometimes observed.

PMID- 19396936
TI  - Varenicline: the French experience after 6 months.

PMID- 19396937
TI  - Do the terms innate and adaptive immunity create conceptual barriers?

PMID- 19396938
TI  - 16S rRNA gene-based phylogenetic microarray for  simultaneous identification of
      members of the genus  Burkholderia.
AB  - For cultivation-independent and highly parallel analysis of members of the genus
      Burkholderia, an oligonucleotide microarray (phylochip) consisting of 131
      hierarchically nested 16S rRNA gene-targeted oligonucleotide probes was
      developed. A novel primer pair was designed for selective amplification of a 1.3
      kb 16S rRNA gene fragment of Burkholderia species prior to microarray analysis.
      The diagnostic performance of the microarray for identification and
      differentiation of Burkholderia species was tested with 44 reference strains of
      the genera Burkholderia, Pandoraea, Ralstonia and Limnobacter. Hybridization
      patterns based on presence/absence of probe signals were interpreted semi
      automatically using the novel likelihood-based strategy of the web-tool Phylo-
      Detect. Eighty-eight per cent of the reference strains were correctly identified
      at the species level. The evaluated microarray was applied to investigate shifts
      in the Burkholderia community structure in acidic forest soil upon addition of
      cadmium, a condition that selected for Burkholderia species. The microarray
      results were in agreement with those obtained from phylogenetic analysis of
      Burkholderia 16S rRNA gene sequences recovered from the same cadmiumcontaminated
      soil, demonstrating the value of the Burkholderia phylochip for determinative and
      environmental studies.

PMID- 19396939
TI  - In this issue of Occupational Medicine.

PMID- 19396940
TI  - The role of single subunits of the DNA transport  machinery of Thermus
      thermophilus HB27 in DNA  binding and transport.
AB  - Thermus thermophilus HB27 is well known for its extraordinary trait of high
      frequencies of natural transformation, which is considered a major mechanism of
      horizontal gene transfer. We show that the DNA translocator of T. thermophilus
      binds and transports DNA from members of all three domains. These results,
      together with the data obtained from genome comparisons, suggest that the DNA
      translocator of T. thermophilus has a major impact in adaptation of Thermus to
      thermal stress conditions and interdomain DNA transfer in extreme hot
      environments. DNA transport in T. thermophilus is mediated by a macromolecular
      transport machinery that consists of at least 16 subunits and spans the
      cytoplasmic membrane and the entire cell periphery. Here, we have addressed the
      role of single subunits in DNA binding and transport. PilQ is involved in DNA
      binding, ComEA, PilF and PilA4 are involved in transport of DNA through the outer
      membrane and PilM, PilN, PilO, PilA1-3, PilC and ComEC are essential for the
      transport of DNA through the thick cell wall layers and/or through the inner
      membrane. These data are discussed in the light of the subcellular localization
      of the proteins. A topological model for DNA transport across the cell wall is
      presented.

PMID- 19396941
TI  - A specific deficit in visuospatial simultaneous working memory in Down syndrome.
AB  - BACKGROUND: Recent studies have demonstrated that individuals with Down syndrome
      (DS) present both central and verbal working memory deficits compared with
      controls matched for mental age, whereas evidence on visuospatial working memory
      (VSWM) has remained ambiguous. The present paper uses a battery of VSWM tasks to
      test the hypothesis that individuals with DS can also encounter specific
      difficulties in VSWM. METHOD: Four tasks were administered to 34 children and
      adolescents with DS and 34 controls matched for verbal mental age. In two of
      these tasks, participants had to remember a series of locations sequentially
      presented on a matrix (spatial-sequential WM); in another two, they had to
      remember locations simultaneously presented (spatial-simultaneous WM). RESULTS
      AND CONCLUSIONS: Results showed that individuals with DS are poorer than controls
      in the spatial-simultaneous tasks, but not in the spatial-sequential tasks. These
      findings were not due to a difference in speed of visuospatial processing. In
      fact, when performances of the two groups in VSWM were compared using speed
      measures as covariates, differences between groups remained. It is suggested that
      the simultaneous VSWM deficit of individuals with DS could be due to the request
      for processing more than one item at a time.

PMID- 19396942
TI  - Isolation of novel bacteria within the Chloroflexi  capable of reductive
      dechlorination of  1,2,3-trichloropropane.
AB  - Two strictly anaerobic bacterial strains were isolated from contaminated
      groundwater at a Superfund site located near Baton Rouge, LA, USA. These strains
      represent the first isolates reported to reductively dehalogenate 1,2,3
      trichloropropane. Allyl chloride (3-chloro-1-propene), which is chemically
      unstable, was produced from 1,2,3-trichloropropane, and it was hydrolysed
      abiotically to allyl alcohol and also reacted with the sulfide- and cysteine
      reducing agents in the medium to form various allyl sulfides. Both isolates also
      dehalogenated a variety of other vicinally chlorinated alkanes (1,2
      dichloropropane, 1,2-dichloroethane, 1,1,2-trichloroethane, 1,1,2,2-
      tetrachloroethane) via dichloroelimination reactions. A quantitative real-time
      PCR (qPCR) approach targeting 16S rRNA genes indicated that both strains couple
      reductive dechlorination to cell growth. Growth was not observed in the absence
      of hydrogen (H2) as an electron donor and a polychlorinated alkane as an electron
      acceptor. Alkanes containing only a single chlorine substituent (1-chloropropane,
      2-chloropropane), chlorinated alkenes (tetrachlorothene, trichlorothene,
      cisdichloroethene, trans-dichloroethene, vinyl chloride) and chlorinated benzenes
      (1-chlorobenzene and 1,2- dichlorobenzene) were not dechlorinated. Phylogenetic
      analysis based on 16S rRNA gene sequence data showed these isolates to represent
      a new lineage within the Chloroflexi. Their closest previously cultured relatives
      are 'Dehalococcoides' strains, with 16S rRNA gene sequence similarities of only
      90%.

PMID- 19396944
TI  - Social determinants of health.

PMID- 19396943
TI  - ECCO 14, The European Cancer Conference was held in Barcelona,  Spain, 23-27
      September 2007. Report by Janet Fricker.

PMID- 19396945
TI  - Volatile organic compounds: a potential direct  long-distance mechanism for
      antagonistic action  of Fusarium oxysporum strain MSA 35.
AB  - Fusarium oxysporum MSA35 [wild-type (WT) strain] is an antagonistic Fusarium that
      lives in association with a consortium of bacteria belonging to the genera
      Serratia, Achromobacter, Bacillus and Stenotrophomonas in an Italian soil
      suppressive to Fusarium wilt. Typing experiments and virulence tests provided
      evidence that the F. oxysporum isolate when cured of the bacterial symbionts [the
      cured (CU) form], is pathogenic, causing wilt symptoms identical to those caused
      by F. oxysporum f. sp. lactucae. Here, we demonstrate that small volatile organic
      compounds (VOCs) emitted from the WT strain negatively influence the mycelial
      growth of different formae speciales of F. oxysporum. Furthermore, these VOCs
      repress gene expression of two putative virulence genes in F. oxysporum lactucae
      strain Fuslat10, a fungus against which the WT strain MSA 35 has antagonistic
      activity. The VOC profile of the WT and CU fungus shows different compositions.
      Sesquiterpenes, mainly caryophyllene, were present in the headspace only of WT
      MSA 35. No sesquiterpenes were found in the volatiles of ectosymbiotic Serratia
      sp. strain DM1 and Achromobacter sp. strain MM1. Bacterial volatiles had no
      effects on the growth of the different ff. spp. of F. oxysporum examined. Hyphae
      grownwithVOCfrom WT F. oxysporum f. sp. lactucae strain MSA 35 were hydrophobic
      whereas those grown without VOCs were not, suggesting a correlation between the
      presence of volatiles in the atmosphere and the phenotype of the mycelium. This
      is the first report of VOC production by antagonistic F. oxysporum MSA35 and
      their effects on pathogenic F. oxysporum. The results obtained in this work led
      us to propose a new potential direct long-distance mechanism for antagonism by F.
      oxysporum MSA 35 mediated by VOCs. Antagonism could be the consequence of both
      reduction of pathogen mycelial growth and inhibition of pathogen virulence gene
      expression.

PMID- 19396946
TI  - Neurogenic inflammation: literature on toluene diisocyanate.

PMID- 19396947
TI  - The effect of nebivolol treatment on oxidative stress  and antioxidant status in
      patients with cardiac  syndrome-X.
AB  - BACKGROUND: Free radical-mediated oxidative stress has been implicated in the
      etiopathogenesis of several disorders. The aim of this study was to elucidate the
      effect of treatment with nebivolol on the metabolic state of oxidative stress,
      and antioxidant status markers in patients with cardiac syndrome-X (CSX),
      additionally, to compare with the effect of metoprolol treatment. METHODS: Thirty
      patients, 17 female and 13 male, with CSX were enrolled in the study. Nebivolol
      (5 mg/day) or metoprolol (50 mg/day) was administrated for 12 weeks. Twelve hour
      fasting blood samples, taken at the initiation and on the third month of therapy,
      were analyzed for the levels of malondialdehyde (MDA), nitrite+nitrate (NOx), and
      the activity of myeloperoxidase (MPO), superoxide dismutase (SOD). No patient
      presented additional risk factors for increased reactive oxygen species levels.
      RESULTS: Compared with sixteen control participants, patients with CSX had
      significantly higher activity of MPO and levels of MDA, but significantly lower
      SOD activity and levels of NOx before treatment. After treatment, MPO activity
      and MDA levels were significantly reduced; SOD activity and NOx levels were
      significantly increased with nebivolol but remained unchanged with metoprolol.
      CONCLUSION: We have shown that patients with CSX who taken nebivolol have lower
      serum MPO activity, levels of MDA and higher serum SOD activity, NOx levels when
      compared with metoprolol treatment. Exercise stress test parameters were also
      ameliorated in patients who had taken nebivolol in contrast to metoprolol.
      Nebivolol treatment may be a novel treatment strategy in cases with CSX in the
      future.

PMID- 19396948
TI  - Microbial DNA metabolism, genome dynamics and human disease.

PMID- 19396950
TI  - 'Candidatus Lumbricincola', a novel lineage of uncultured Mollicutes from
      earthworms of family Lumbricidae.
AB  - Molecular signatures of new, as yet uncultured mollicute-like organisms (MLOs)
      have been detected in total rRNA and DNA extracted from tissues, gut contents and
      casts of four species of the earthworm family Lumbricidae. The MLO 16S rRNA
      sequences exhibited low identity to those of known Mollicutes species and formed
      a monophyletic cluster distantly affiliated to the 'Candidatus Bacilloplasma'
      (84.9%) and almost equidistant to the other main phylogenetic group of Mollicutes
      (< 79.8%) and the classes Bacilli (< 79.5%) and Clostridia (< 76.1%). SSCP
      profiling and sequence analysis of bands and bacterial clones derived from the
      earthworms and substrata revealed high phylogenetic relatedness of MLOs in
      earthworms from different geographic locations (Russia and Germany), with no
      obvious host species specificity being observed. Fluorescence in situ
      hybridization (FISH) analysis with a nucleotide probe specific for the new MLO
      group localized them to the coelomic fluids of earthworms. A new taxonomic group
      within the Mollicutes, designated 'Candidatus Lumbricincola', is proposed to
      include these as yet uncultured organisms.

PMID- 19396949
TI  - Genome dynamics in major bacterial pathogens.
AB  - Pathogenic bacteria continuously encounter multiple forms of stress in their
      hostile environments, which leads to DNA damage. With the new insight into
      biology offered by genome sequences, the elucidation of the gene content encoding
      proteins provides clues toward understanding the microbial lifestyle related to
      habitat and niche. Campylobacter jejuni, Haemophilus influenzae, Helicobacter
      pylori, Mycobacterium tuberculosis, the pathogenic Neisseria, Streptococcus
      pneumoniae, Streptococcus pyogenes and Staphylococcus aureus are major human
      pathogens causing detrimental morbidity and mortality at a global scale. An
      algorithm for the clustering of orthologs was established in order to identify
      whether orthologs of selected genes were present or absent in the genomes of the
      pathogenic bacteria under study. Based on the known genes for the various
      functions and their orthologs in selected pathogenic bacteria, an overview of the
      presence of the different types of genes was created. In this context, we focus
      on selected processes enabling genome dynamics in these particular pathogens,
      namely DNA repair, recombination and horizontal gene transfer. An understanding
      of the precise molecular functions of the enzymes participating in DNA metabolism
      and their importance in the maintenance of bacterial genome integrity has also,
      in recent years, indicated a future role for these enzymes as targets for
      therapeutic intervention.

PMID- 19396951
TI  - Single injection of a low dose of pentylenetetrazole leads to epileptogenesis in
      an animal model of cortical dysplasia.
AB  - PURPOSE: Cortical dysplasia (CD) is one of the most frequent causes of
      pharmacoresistent focal epilepsy. Despite significant advances in various
      diagnostic and therapeutic methods, the basic mechanisms of higher susceptibility
      for seizures in patients with CD are unknown. Animal models of CD present with a
      lower threshold for seizure induction. The purpose of this study is to further
      characterize the animal model of in utero radiation-induced CD and to illustrate
      the effect of a late postnatal second hit (low dose of pentylenetetrazole, PTZ)
      on the development of spontaneous seizures. METHODS: Pregnant Sprague-Dawley rats
      were irradiated on E17 (145 cGy; control group was left untreated). Litters were
      implanted with bifrontal epidural and hippocampal depth electrodes. After
      baseline electroencephalography (EEG) recording, animals received 30 mg/kg PTZ
      and were chronically monitored. Histopathology of the brains was verified.
      RESULTS: No seizures were detected in animals that did not receive PTZ. PTZ
      injected irradiated (XRT) rats showed severe prolonged, repetitive seizures
      during the acute period. During the chronic period, XRT rats had recurrent
      seizures and epileptiform spikes. PTZ-injected control animals exhibited milder
      and fewer acute seizures and did not show seizures during the chronic period.
      Histology was consistent with cortical and hippocampal dysplasia. CONCLUSIONS:
      This study shows that a single treatment with a low dose of PTZ renders XRT rats
      (but not age-matched controls) epileptic, exhibiting spontaneous epileptiform
      spikes and seizures on EEG. These results might mirror the natural history of
      patients with CD thought to be caused by prenatal/congenital or perinatal
      insults.

PMID- 19396952
TI  - EEG stages predict treatment response in experimental status epilepticus.
AB  - Progression of severity in experimental status epilepticus (SE), defined as
      refractoriness to first- and second-line abortive agents, may be related to a
      five-stage progression of electroencephalography (EEG) patterns. This was tested
      in the lithium-pilocarpine rat SE model. Abortive treatment with diazepam and
      phenobarbital was given at EEG stages I, III, and V. In stage I, the combination
      therapy resulted in 100% SE termination. However, stage III corresponded to high
      treatment resistance (0% abortion) and stage V to an intermediate response (63%).
      Comparisons of time-to-treatment durations showed overlap between stage I and
      stage III, despite having markedly different response rates to abortive
      medications. Therefore, EEG patterns reflect the dynamic pathophysiology of SE
      and can be used as reliable and specific markers to distinguish treatment
      responsive from treatment-refractory SE more accurately than time alone.

PMID- 19396953
TI  - Hepatitis B: significant advances and unmet challenges.

PMID- 19396955
TI  - Cholestasis and cholestatic syndromes.
AB  - PURPOSE OF REVIEW: Cholestatic liver injury is encountered across a wide variety
      of clinical scenarios ranging from toxin-induced, genetic, to autoimmune in
      nature. This review summarizes recent findings from what is a burgeoning clinical
      field. RECENT FINDINGS: We highlight observations from cell biology
      (intracellular signaling molecules), genetics (biliary transporters) and clinical
      studies (predictors of outcomes) that provide new directions for laboratory and
      clinical research. SUMMARY: Treatments for cholestasis and cholestatic syndromes
      remain largely nonspecific and often ineffective. With the increased precision
      with which the cell biology of the cholangiocyte and the clinical description of
      associated diseases such as primary biliary cirrhosis and sclerosing cholangitis
      are understood, new approaches are likely to arise.

PMID- 19396954
TI  - Pilin gene variation in Neisseria gonorrhoeae: reassessing the old paradigms.
AB  - Neisseria gonorrhoeae displays considerable potential for antigenic variation as
      shown in human experimental studies. Various surface antigens can change either
      by antigenic variation using RecA-dependent recombination schemes (e.g. PilE
      antigenic variation) or, alternatively, through phase variation (on/off
      switching) in a RecA-independent fashion (e.g. Opa and lipooligosaccharide phase
      variation). PilE antigenic variation has been well documented over the years.
      However, with the availability of the N. gonorrhoeae FA1090 genome sequence,
      considerable genetic advances have recently been made regarding the mechanistic
      considerations of the gene conversion event, leading to an altered PilE protein.
      This review will compare the various models that have been presented and will
      highlight potential mechanistic problems that may constrain any genetic model for
      pilE gene variation.

PMID- 19396956
TI  - Portal hypertension.
AB  - PURPOSE OF REVIEW: Portal hypertension is the most common complication of
      cirrhosis accounting for significant morbidity and mortality mainly because of
      variceal hemorrhage, ascites, bacterial infections, hepatic encephalopathy, and
      hepatorenal syndrome. Advances in the diagnosis and management of portal
      hypertension over the last year are reviewed. RECENT FINDINGS: The measurement of
      the hepatic venous pressure gradient provides important prognostic information in
      patients with portal hypertension. Noninvasive testing with transient
      elastography, capsule endoscopy, and computed tomography scanning for the
      diagnosis of esophageal varices is promising but more information is needed.
      Easily obtainable clinical data have been identified in patients with acute
      variceal bleeding that provides important information in determining initial
      response to therapy and prognosis. New therapies for patients with dilutional
      hyponatremia with vasopressin antagonists are promising and may improve the
      management of this condition. Terlipressin is the best medical therapy currently
      available for the management of hepatorenal syndrome as confirmed in recent
      studies. Patients with advanced liver disease benefit from the long-term
      administration of norfloxacin as it prevents the development of hepatorenal
      syndrome and improves survival. SUMMARY: The ongoing advances in the diagnosis
      and management of patients with cirrhosis and portal hypertension will improve
      the high morbidity and mortality of the complications of cirrhosis

PMID- 19396957
TI  - Genesis, effects and fates of repeats in prokaryotic genomes.
AB  - DNA repeats are causes and consequences of genome plasticity. Repeats are created
      by intrachromosomal recombination or horizontal transfer. They are targeted by
      recombination processes leading to amplifications, deletions and rearrangements
      of genetic material. The identification and analysis of repeats in nearly 700
      genomes of bacteria and archaea is facilitated by the existence of sequence data
      and adequate bioinformatic tools. These have revealed the immense diversity of
      repeats in genomes, from those created by selfish elements to the ones used for
      protection against selfish elements, from those arising from transient gene
      amplifications to the ones leading to stable duplications. Experimental works
      have shown that some repeats do not carry any adaptive value, while others allow
      functional diversification and increased expression. All repeats carry some
      potential to disorganize and destabilize genomes. Because recombination and
      selection for repeats vary between genomes, the number and types of repeats are
      also quite diverse and in line with ecological variables, such as host-dependent
      associations or population sizes, and with genetic variables, such as the
      recombination machinery. From an evolutionary point of view, repeats represent
      both opportunities and problems. We describe how repeats are created and how they
      can be found in genomes. We then focus on the functional and genomic consequences
      of repeats that dictate their fate.

PMID- 19396958
TI  - Versatility of choline metabolism and choline-binding proteins in Streptococcus
      pneumoniae and commensal streptococci.
AB  - The pneumococcal choline-containing teichoic acids are targeted by cholinebinding
      proteins (CBPs), major surface components implicated in the interaction with host
      cells and bacterial cell physiology. CBPs also occur in closely related commensal
      species, Streptococcus oralis and Streptococcus mitis, and many strains of these
      species contain choline in their cell wall. Physiologically relevant CBPs
      including cell wall lytic enzymes are highly conserved between Streptococcus
      pneumoniae and S. mitis. In contrast, the virulence-associated CBPs, CbpA, PspA
      and PcpA, are S. pneumoniae specific and are thus relevant for the characteristic
      properties of this species.

PMID- 19396959
TI  - Regulation of natural genetic transformation and acquisition of transforming DNA
      in Streptococcus pneumoniae.
AB  - The ability of pneumococci to take up naked DNA from the environment and
      permanently incorporate the DNA into their genome by recombination has been
      exploited as a valuable research tool for 80 years. From being viewed as a
      marginal phenomenon, it has become increasingly clear that horizontal gene
      transfer by natural transformation is a powerful mechanism for generating genetic
      diversity, and that it has the potential to cause severe problems for future
      treatment of pneumococcal disease. This process constitutes a highly efficient
      mechanism for spreading beta-lactam resistance determinants between streptococcal
      strains and species, and also threatens to undermine the effect of pneumococcal
      vaccines. Fortunately, great progress has been made during recent decades to
      elucidate the mechanism behind natural transformation at a molecular level.
      Increased insight into these matters will be important for future development of
      therapeutic strategies and countermeasures aimed at reducing the spread of
      hazardous traits. In this review, we focus on recent developments in our
      understanding of competence regulation, DNA acquisition and the role of natural
      transformation in the dissemination of virulence and beta-lactam resistance
      determinants.

PMID- 19396960
TI  - Hepatic fibrosis.
AB  - PURPOSE OF REVIEW: This review will summarize the most significant work that
      contributed to the understanding of liver fibrosis progression and resolution,
      which in turn has yielded new areas of therapeutic targeting. RECENT FINDINGS:
      Liver fibrosis is the result of an imbalance between production and dissolution
      of extracellular matrix. Stellate cells, portal myofibroblasts, and bone marrow
      derived cells converge in a complex interaction with hepatocytes and immune cells
      to provoke scarring in response to liver injury. Uncovering the specific effects
      of growth factors on these cells, defining the interaction of different cell
      population during liver fibrosis and characterizing the genetic determinants of
      fibrosis progression will enable the discovery of new therapeutic approaches.
      SUMMARY: The outcome of improved understanding of liver fibrosis process,
      especially the regulation and activation of stellate cells, is reflected in the
      development of new therapeutic strategies, which are validated in animal models.

PMID- 19396962
TI  - Recent advances in nonalcoholic fatty liver disease.
AB  - PURPOSE OF REVIEW: This review focuses on recent advances in the study of the
      epidemiology, pathogenesis, natural history and treatment of nonalcoholic fatty
      liver disease (NAFLD). RECENT FINDINGS: Study of hepatic lipid metabolism with
      respect to the contribution of de-novo lipogenesis to hepatic steatosis and
      insulin resistance and the dysregulation of cellular adaptive response to stress,
      that is, the unfolded protein response has added to our current understanding of
      NAFLD. microRNA has recently emerged and has been shown to be differentially
      expressed in patients with nonalcoholic steatohepatitis. Its mechanism of action
      remains to be further explored. There is no proven pharmacotherapy for the
      treatment of NAFLD. Lifestyle intervention to achieve weight loss and increase
      exercise is persistently associated with improved liver histology. The diagnostic
      utility of noninvasive markers and imaging modalities in assessing fibrosis
      remains to be elucidated. SUMMARY: The underlying mechanism and pathogenesis of
      NAFLD remain elusive. Although research effort has advanced the understanding of
      the natural history, pathogenesis and management of the disease, there is no
      proven therapy for this medical condition. At present, treatment concentrates on
      managing underlying metabolic risk factors.

PMID- 19396961
TI  - The diversity of conjugative relaxases and its application in plasmid
      classification.
AB  - Bacterial conjugation is an efficient and sophisticated mechanism of DNA transfer
      among bacteria. While mobilizable plasmids only encode a minimal MOB machinery
      that allows them to be transported by other plasmids, conjugative plasmids encode
      a complete set of transfer genes (MOB1T4SS). The only essential ingredient of the
      MOB machinery is the relaxase, the protein that initiates and terminates
      conjugative DNA processing. In this review we compared the sequences and
      properties of the relaxase proteins contained in gene sequence databases.
      Proteins were arranged in families and phylogenetic trees constructed from the
      family alignments. This allowed the classification of conjugative transfer
      systems in six MOB families:MOB(F), MOB(H), MOB(Q), MOB(C), MOB(P) and MOB(V).
      The main characteristics of each family were reviewed. The phylogenetic
      relationships of the coupling proteins were also analysed and resulted in
      phylogenies congruent to those of the cognate relaxases. We propose that the
      sequences of plasmid relaxases can be used for plasmid classification. We hope
      our effort will provide researchers with a useful tool for further mining and
      analysing the plasmid universe both experimentally and in silico.

PMID- 19396963
TI  - Bile duct cysts: contemporary surgical management.
AB  - PURPOSE OF REVIEW: Surgical treatment of bile duct cysts remains the mainstay to
      reduce cyst-related complications and risk of malignancy. Optimizing treatment
      outcomes is dependent upon a thorough preoperative evaluation and selecting the
      appropriate intervention. This review summarizes the recent progress in the
      evaluation and treatment of bile duct cysts, particularly in relation to
      contemporary operative approaches. RECENT FINDINGS: Ongoing efforts continue in
      optimizing the evaluation, classification and management of bile duct cysts. The
      risk of cholangiocarcinoma is not limited to the bile duct cyst itself and
      appropriate management and surveillance is paramount. Recent advances in
      laparoscopic and endoscopic equipment have paralleled an increasing interest in
      minimally invasive approaches in the management of patients with bile duct cysts.
      Favorable results of laparoscopic approaches are increasingly reported and
      suggest the feasibility of this technique in select patients. SUMMARY: Although
      the surgical premise of resection has not changed for the treatment of bile duct
      cysts, there has been an increasing utilization of minimally invasive approaches.
      Results thus far are promising, but long-term, controlled data is needed before
      this approach can be considered standard.

PMID- 19396964
TI  - Inflammation and biliary tract injury.
AB  - PURPOSE OF REVIEW: Primary biliary cirrhosis, primary sclerosing cholangitis and
      biliary atresia are thought to be immune-mediated cholangiopathies, however, gaps
      in knowledge remain with regard to the immunopathogenesis of these diseases.
      RECENT FINDINGS: In this review, we highlight recent investigations pertaining to
      the role of both innate and adaptive immunity in bile duct damage. In innate
      immunity, evidence is presented for the contribution of cholangiocyte toll-like
      receptor stimulation promoting the ongoing inflammatory response. Innate-like
      lymphocytes may also be critical in the early phases of small bile duct injury
      found in primary biliary cirrhosis. With regard to adaptive immunity, the role of
      specific gene deficiencies in the susceptibility to immune-mediated
      cholangiopathies is reviewed. Furthermore, recent work analyzing the effector
      mechanisms of adaptive immunity leading to bile duct epithelial apoptosis are
      outlined. SUMMARY: Understanding the intricacies of the inflammatory mechanisms
      culminating in bile duct epithelial injury are crucial to the future development
      of therapies aimed at halting the ongoing biliary tract destruction found in
      immune-mediated cholangiopathies. A paucity of research studies on primary
      sclerosing cholangitis was noted in this review and future research efforts
      should focus on primary sclerosing cholangitis, in addition to primary biliary
      cirrhosis and biliary atresia.

PMID- 19396965
TI  - Serum and bile biomarkers for cholangiocarcinoma.
AB  - PURPOSE OF REVIEW: To discuss recent studies proposing new markers in serum or
      bile for the diagnosis and prognosis of cholangiocarcinoma (CCA), which could
      help in the differential diagnosis between malignant and benign biliary disorders
      or for the surveillance of disorders at risk, including primitive sclerosing
      cholangitis. RECENT FINDINGS: In the last few years, efforts have been made to
      identify biomarkers with adequate diagnostic accuracy for CCA in serum or
      biological fluid. Studies have been focused on cytokines, growth factors or
      enzymes produced and secreted by CCA cells as well as on the proteomic analysis
      of serum and bile. SUMMARY: The serum levels of interleukin 6, trypsinogen, mucin
      5AC, soluble fragment of cytokeratin 19 and the platelet-lymphocyte ratio have
      been recently shown to help in the diagnosis of CCA with, in some cases, a
      prognostic value. As far as bile is concerned, the ratio of pancreatic
      elastase/amylase, mucin-4, minichromosome maintenance replication protein and
      insulin-like growth factor 1 have been explored, with the insulin-like growth
      factor 1 biliary concentration capable of completely discriminating CCA from
      benign biliary disorders and pancreatic cancer. We have also discussed advances
      in the proteomic of serum and bile, which seem promising in identifying new
      markers for CCA.

PMID- 19396966
TI  - [Bicycling legs].

PMID- 19396967
TI  - Practical ethics. Delay upsets donor.

PMID- 19396968
TI  - [Accompanying patients in substitution treatment for opiates: consulting and
      coaching in the office]].

PMID- 19396969
TI  - [The phylogenetic role of ontogenies (recapitulation and morphogenesis)].
AB  - Different approaches to evolutionary interpretation of ontogenies are compared,
      with special emphasis on the evolutionary role of morphogenetic mechanisms
      (construction technologies) substantially affecting the structure of definitive
      forms: they largely determine the structural characteristics of organs, types of
      anatomical and histological systems, and specificity of symmetry of organisms and
      their parts. The role of cellular morphogenesis inherited from protozoic
      ancestors in the morphogenesis of multicellular organisms is demonstrated. Two
      main ways of improving morphogeneses are considered, based on epithelial
      morphogenesis and early determined few-celled primordial. On the one hand, the
      phylogenetic role of archallaxes and deviations is emphasized, these events often
      switching evolution to a fundamentally new direction. On the other hand, many
      characteristics of developmental stages are explainable by rationalization of
      morphogeneses and do not recapitulate ancestral forms, which should be taken into
      consideration in phylogenetic interpretation of embryogeneses; in particular,
      this applies to interpretation of axial relationships.

PMID- 19396970
TI  - [Evolutionary conditioning of response to changes in ionic composition of water
      in hydrobionts: an example of freshwater zooplankton].
AB  - The situation in Karelian water bodies polluted with mining waste has been
      analyzed. As a result of technogenic wastewater discharge, the total ion content
      in lake waters has increased tens of times, and the concentration of potassium
      ions (the main component of wastewater), hundreds of times. Pollution tolerance
      of hydrobiont populations depends on the historically developed adaptation
      potential of species. The lowest tolerance to mineral pollution is characteristic
      of crustaceans representing mesolimnic families Polyphemidae, Sididae,
      Leptodoridae, Holopedidae, Diaptomidae, and Temoridae. Representatives of
      paleolimnic cristacean families Daphniidae, Bosminidae, and Cycopidae as well
      rotifer (Rotatoria) species of freshwater origin are highly tolerant of changes
      in the ionic composition of water.

PMID- 19396971
TI  - Obama's $19 billion boon to health care IT: mammoth investment fasttracks
      electronic health records.

PMID- 19396972
TI  - Biomarkers for tuberculosis disease status and diagnosis.
AB  - PURPOSE OF REVIEW: Every year, over 8 million people develop tuberculosis and
      nearly 1.8 million die from it, despite extensive vaccination and drug treatment
      programmes. It is increasingly recognized that the diagnosis of tuberculosis,
      which relies heavily on century-old techniques, is one of the weakest links in
      the chain of tuberculosis control, hampering not just treatment but also the
      development of new drugs and vaccines. As a result, recent years have seen the
      initiation of large-scale studies aiming to identify biomarkers of Mycobacterium
      tuberculosis infection and disease. This review discusses initial results and
      future prospects for that work. RECENT FINDINGS: The key finding from recent work
      has been that no one factor seems able to explain the complex course of
      Mycobacterium tuberculosis infection. Multifactorial analyses have identified a
      variety of genes and proteins, mostly involved in bacterial persistence or host
      responses, that offer promise as biomarkers for different disease stages.
      SUMMARY: The challenge now is to validate the suggested biomarkers being
      described and then reduce them to clinical practice. If this can be done, it
      offers the possibility of greatly improved clinical management of tuberculosis,
      allowing segregation of patients and contacts into appropriate treatment
      regimens.

PMID- 19396973
TI  - Conformations of NhaA, the Na+/H+ exchanger from Escherichia coli, in the pH
      activated and ion-translocating states.
AB  - NhaA, the main sodium-proton exchanger in the inner membrane of Escherichia coli,
      regulates the cytosolic concentrations of H+ and Na+. It is inactive at acidic
      pH, becomes active between pH 6 and pH 7, and reaches maximum activity at pH 8.
      By cryo-electron microscopy of two-dimensional crystals grown at pH 4 and
      incubated at higher pH, we identified two sequential conformational changes in
      the protein in response to pH or substrate ions. The first change is induced by a
      rise in pH from 6 to 7 and marks the transition from the inactive state to the pH
      activated state. pH activation, which precedes the ion-induced conformational
      change, is accompanied by an overall expansion of the NhaA monomer and a local
      ordering of the N-terminus. The second conformational change is induced by the
      substrate ions Na+ and Li+ at pH above 7 and involves a 7-A displacement of helix
      IVp. This movement would cause a charge imbalance at the ion-binding site that
      may trigger the release of the substrate ion and open a periplasmic exit channel.

PMID- 19396974
TI  - Patient advocacy groups: empowering patients in their fight against cancer.

PMID- 19396975
TI  - Infrastructure for translational research in Asia.

PMID- 19396976
TI  - On using a normal approximation for the noncentral t-distribution in determining
      upper limits for future sample relative repeatability and reproducibility
      standard deviations.
AB  - Formulas, based on a normal approximation for the noncentral t-distribution, were
      developed to compute 100p% one-tailed upper limits for future sample relative
      repeatability and relative reproducibility standard deviations (RSDr,% and
      RSDR,%) collaboratively obtained under a completely randomized model. The
      accuracy of the formulas for obtaining a one-tailed upper limit for the future
      sample RSDr,% was assessed by comparing the computed noncentral t-distribution
      based upper limits with the one-tailed upper limits based on a normal
      approximation for the noncentral t-distribution. The accuracy of the normal
      approximation formula for obtaining a one-tailed upper limit for a future sample
      RSDR,% was assessed by comparing the formula-based one-tailed upper limits with
      those obtained in a Monte Carlo simulation study.

PMID- 19396977
TI  - [Cost-benefit analysis of the program on early detection of pulmonary diseases].
AB  - BACKGROUND: Economic evaluation of costs and effectiveness of the program aimed
      at early detection of lung diseases was the subject of the study. The scope of
      the study is related to the European tendency of creating information resources
      for public resources management. MATERIAL AND METHODS: The study covered more
      than 14 000 people divided into three age groups, living in 11 localities in the
      Lodz region. The program aimed at lung diseases detection was conducted in three
      steps: first specialist examinations, X-ray examinations, second specialist
      examinations. Costs and effectiveness of the program were compared by
      cost/effectiveness and incremental ratios. RESULTS: The results of the study were
      formulated in the following areas: costs of the program by age groups and groups
      with suspected diseases, effects of the program, costs per one detected case and
      incremental ratios. DISCUSSION AND CONCLUSIONS: The results of the study show
      that economic evaluation conducted from ex post perspective could be useful in
      building decision scenarios. Sensitivity analysis allows for investigating how
      different assumptions of variables influence the study results. Variables useful
      for the scenarios of early lung diseases detection programs were identified for
      further studies.

PMID- 19396978
TI  - Ready or not? Protecting the public's health from diseases, disasters, and
      bioterrorism.

PMID- 19396979
TI  - Metabolic evolution suggests an explanation for the weakness of antioxidant 
      defences in beta-cells.
AB  - The lack of an effective antioxidant system in beta-cells, which renders them
      susceptible to oxidative stress, is to date without explanation. The particular
      weakness of beta-cells in females, in both humans and mice, is another
      unexplained observation. We hypothesise that reactive oxygen species (ROS) in
      beta-cells, by their negative effect on insulin synthesis/secretion, play a
      fitness-enhancing role for the whole organism. Under stress conditions, the
      release of stress hormones produces insulin resistance and, owing to ROS
      preventing beta-cells from secreting insulin at the level required to maintain
      homeostasis, diverts glucose to insulin-independent tissues such as the brain and
      the foetus. We suggest that pancreatic beta-cells lost part of their antioxidant
      defence in association with brain evolution, and lost even more in females when
      placental mammals evolved. The unusual antioxidant status of beta-cells may thus
      be explained as an instance of co-evolution of the brain, cortisol and
      corticosteroid receptors, and beta-cells in the endocrine pancreas.

PMID- 19396980
TI  - Altered senescence, apoptosis, and DNA damage response in a mutant  p53 model of
      accelerated aging.
AB  - The tumor suppressors p16(INK4a) and p53 have been implicated as contributors to
      age-associated stem cell decline. Key functions of p53 are the induction of cell
      cycle arrest, senescence, or apoptosis in response to DNA damage. Here, we
      examine senescence, apoptosis, and DNA damage responses in a mouse accelerated
      aging model that exhibits increased p53 activity, the p53(+/m) mouse. Aged
      tissues of p53(+/m) mice display higher percentages of senescent cells (as
      determined by senescence-associated beta-galactosidase staining and p16(INK4a)
      and p21 accumulation) compared to aged tissues from p53(+/+) mice. Surprisingly,
      despite having enhanced p53 activity, p53(+/m) lymphoid tissues exhibit reduced
      apoptotic activity in response to ionizing radiation compared to p53(+/+)
      tissues. Ionizing radiation treatment of p53(+/m) tissues also induces higher and
      prolonged levels of senescence markers p16(INK4a) and p21, suggesting that in
      p53(+/m) tissues the p53 stress response is enhanced and is shifted away from
      apoptosis toward senescence. One potential mechanism for accelerated aging in the
      p53(+/m) mouse is a failure to remove damaged or dysfunctional cells (including
      stem and progenitor cells) through apoptosis. The increased accumulation of
      dysfunctional and senescent cells may contribute to reduced tissue regeneration,
      tissue atrophy, and some of the accelerated aging phenotypes in p53(+/m) mice.

PMID- 19396982
TI  - Treating criminal offenders: where things stand.

PMID- 19396981
TI  - Changes in IL-15 expression and death-receptor apoptotic signaling in rat 
      gastrocnemius muscle with aging and life-long calorie restriction.
AB  - TNF-alpha-mediated apoptosis is enhanced in aged rodent muscles, suggesting that
      this pathway may be involved in sarcopenia. Interleukin-15 (IL-15), a muscle
      derived anabolic cytokine, mitigates muscle wasting and apoptosis in cachectic
      rats. This effect is thought to occur through inhibition of TNF-alpha-triggered
      apoptosis. We investigated IL-15 signaling and the TNF-alpha-mediated pathway of
      apoptosis in the gastrocnemius muscle of Fischer344xBrown Norway rats across the
      ages of 8, 18, 29 and 37 months, in relation to life-long calorie restriction
      (CR, 40% calorie intake reduction). Aging caused loss of muscle mass and
      increased apoptotic DNA fragmentation, which were mitigated by CR. Protein levels
      of IL-15 and mRNA abundance of IL-15 receptor a-chain decreased in senescent ad
      libitum (AL) fed rats, but were maintained in CR rodents. Elevations of TNF
      alpha, TNF-receptor 1, cleaved caspase-8 and -3 were observed at advanced age in
      AL rats. These changes were prevented or mitigated by CR. Our results indicate
      that aging is associated with decreased IL-15 signaling in rat gastrocnemius
      muscle, which may contribute to sarcopenia partly through enhanced TNF-alpha
      mediated apoptosis. Preservation of IL-15 signaling by CR may therefore represent
      a further mechanism contributing to the anti-aging effect of this dietary
      intervention in skeletal muscle.

PMID- 19396983
TI  - A Tribute to Eberhard F. Mammen, M.D. (1930-2008). Special issue.

PMID- 19396984
TI  - Temporal trends in testosterone levels and treatment in  older men.
AB  - PURPOSE OF REVIEW: Longitudinal studies of testosterone concentrations have
      yielded sharper estimates of age-related androgen declines than their cross
      sectional counterparts. A potential explanation for this phenomenon is a secular
      (age independent) mechanism acting to accelerate within-individual testosterone
      decreases with time. This article reviews the evidence in favor of such secular
      trends and discusses potential causes and implications. RECENT FINDINGS: The
      magnitude of the proposed secular trend may be as much as 1% per calendar year in
      excess of per year cross-sectional trends. Current evidence suggests that body
      composition changes as expressed by BMI can in part account for the trend in
      testosterone. More speculative recent findings suggest a potential contributory
      role for environmental endocrine disruptors, but to date no longitudinal studies
      have examined this question. Symptomatic androgen deficiency as currently defined
      is associated with diverse downstream morbidity, but may not constitute a robust
      designation over longer term periods of time. Information concerning treatment
      patterns in the general population is limited. SUMMARY: Existing evidence, though
      limited, supports the hypothesis of secular declines in serum testosterone levels
      in adult men. It is conceivable that these trends may influence the health of the
      public. Studies confirming and accounting for these trends are needed.

PMID- 19396985
TI  - Androgen therapy for delayed male puberty.
AB  - PURPOSE OF REVIEW: Delayed puberty in men is a commonly presenting problem to
      paediatricians and an understanding of the available evidence on cause,
      treatments and outcomes is important to guide practice. RECENT FINDINGS:
      Understanding of the regulation of the onset of puberty is gradually unfolding,
      although the genetic factors that dictate the timing of puberty in individuals
      and families remain poorly elucidated. Mutations and polymorphisms in candidate
      genes are being actively studied and it is likely that there is significant
      overlap between traditional diagnostic categories. Also, environmental endocrine
      disruptors may interact with the genetic regulation of puberty. Delayed puberty
      may not always be a benign condition, with increased risks of failing to achieve
      target height, adverse psychological and educational consequences, delayed sexual
      and psychosocial integration into society and effects on skeletal proportions and
      bone mass reported. Appropriate evaluation and follow-up is needed to guide
      clinical practice, particularly to distinguish constitutional delay in growth and
      puberty from that associated with other medical disease or permanent disorders.
      SUMMARY: In milder cases of delayed puberty, treatment is often not required;
      however, considerable evidence exists for the efficacy and safety of short
      courses of low-dose testosterone therapy for appropriately selected individuals.
      This treatment is associated with high levels of patient satisfaction. There is
      not yet sufficient evidence for the routine use of other therapies (e.g. growth
      hormone, aromatase inhibitors) for constitutional delay in growth and puberty and
      better characterization of cause may lead to more targeted individual therapy.

PMID- 19396986
TI  - Androgens and hair loss.
AB  - PURPOSE OF REVIEW: Androgenetic alopecia (AGA) or male pattern hair loss is a
      very common condition that has a significant psychosocial impact for patients.
      Many advances in the pathogenesis and treatment of AGA have been discovered
      recently. We discuss the pathogenesis and treatment of AGA. RECENT FINDINGS: Wide
      genome analysis showed an association of AGA and chromosome 20pll in addition to
      androgen-receptor gene. Also, a locus on chromosome 3q26 was found to have a
      linkage with AGA. Dutasteride has been shown to be more effective than
      finasteride in the treatment of AGA but is not yet a recommended therapy. In an
      in-vitro study, a new topical liposomal finasteride formulation showed more than
      five-fold higher deposition of drug in skin than the corresponding plain drug
      solution. SUMMARY: These recent developments in the field of AGA hold some
      promise and may play a role in the future management.

PMID- 19396987
TI  - Transfer of reducing equivalents across the mitochondrial membrane. I. Hydrogen
      transfer mechanisms involved in the reduction of pyruvate to lactate in isolated
      liver cells.
AB  - (1) The reduction of pyruvate to lactate has been studied in isolated liver cells
      in order to elucidate the mechanims involved in the transfer of reducing
      equivalents from mitochondria to cytosol. (2) Manipulation of the cytosolic
      oxaloacetate concentration did not support the malate-oxaloacetate cycle as being
      responsible for the transfer of reducing equivalents out of the mitochondria: (a)
      With pyruvate plus oleate present 2 mM Amytal caused a 10-fold decrease in the
      oxaloacetate concentration, but had only a small inhibitory effect on lactate
      production. Oleate was essential in order to prevent disintegration of the cells
      in the presence of Amytal. (b) Quinolinate, an inhibitor of phosphoenolpyruvate
      carboxylase (GTP: oxaloacetate carboxylyase, transphosphorylating, EC 4.1.1.32),
      caused a several-fold increase in the oxaloacetate concentration but inhibited
      lactate production from pyruvate; this was accompanied by an increased reduction
      of mitochondrial pyridine nucleotides. (3) p-Chlorophenyl pyruvate, an inhibitor
      of pyruvate carboxylase (pyruvate: carbondioxide ligase, ADP, EC 6.4.1.1), also
      inhibited lactate production from pyruvate. (4) It is postulated that with
      pyruvate as substrate, recycling of carbon via pyruvate carboxylase,
      phosphoenolpyruvate carboxylase and pyruvate kinase (ATP: pyruvate
      phosphotransferase, EC 2.7.1.40) is an important, energy-requiring, mechanism for
      the transfer of the proportion of NADH not directly associated with
      gluconeogenesis.

PMID- 19396988
TI  - The binding of uncouplers of oxidative phosphorylation to rat-liver mitochondria.
AB  - The binding of different uncouplers of oxidative phosphorylation to rat-liver
      mitochondria was measured. At pH 7.2 and about 0.7 mg mitochondrial protein/ml
      the percentage bound of the uncoupler added was 84% for 2,3,4,5,6
      pentachlorophenol (PCP), 40% for carbonyl cyanide p
      trifluoromethoxyphenylhydrazone (FCCP), 35% for 4,5,6,7-tetrachloro-2
      trifluoromethylbenzimidazole (TTFB), 4% for alpha,alpha'
      bis(hexafluoroacetonyl)acetone (1799), and less than 4% for 2,4-dinitrophenol.
      These percentages are constant up to amounts of uncoupler added several times the
      one needed for maximal uncoupling. The values found for FCCP and TTFB are in
      contradiction to the proposed stoichiometric interaction of uncouplers with the
      coupling sites of the mitochondrial membrane. From titration experiments of the
      rate of O2 uptake by rat-liver mitochondria in State 4 as a function of the
      uncoupler concentration in the presence of albumin or of different types of
      liposomes the conclusion is drawn that the negative surface charge of the
      mitochondrial phospholipids may be an important parameter in determining the
      binding of anionic uncouplers to rat-liver mitochondria.

PMID- 19396989
TI  - The comparative uptake of Ba2+ and other alkaline earth metals by plant
      mitochondria.
AB  - (1) The transport of Ba2+ by mung bean (Phaseolus aureus L) mitochondria is
      examined and its uptake properties compared with the accumulation of other
      alkaline earth metals by plant mitochondria. Uptake is supported by oxidizable
      substrates but not by ATP under the conditions examined. Ba2+ uptake shows an
      absolute requirement for Pi, whereas AsO4, acetate and oxalate do not replace Pi.
      ATP synthesis inhibits Ba2+ uptake 50% and both 2,4-dinitrophenol and valinomycin
      plus K+ inhibit uptake over 80%. (2) The relative capacity to transport a series
      of alkaline earth metals showed a preferred order of: Sr2+ > Ca2+ > Ba2+ >> Mg2+.
      Mitochondria isolated from three plant sources showed net levels of Mg2+ uptake
      7% or less than the observed Sr2+ uptake values. The same relative order of
      alkaline earth metal supported uptake of Pi was observed with bean (Phaseolus
      vulgaris L) mitochondria. It is suggested that salt transport in plant
      mitochondria involves a carrier complex which binds both divalent cations and Pi.

PMID- 19396990
TI  - Cytochrome oxidase from Pseudomonas aeruginosa. III. Reduction of hydroxylamine.
AB  - Pseudomonas aeruginosa cytochrome oxidase, which reduces nitrite and oxygen, is
      also capable of reducing hydroxylamine to ammonia. The Km for hydroxylamine
      reduction is 6 x 10(-4) M compared to 5 x 10(-5) M for nitrite reduction. NADH,
      NADPH, reduced P. aeruginosa cytochrome c551, and reduced P. aeruginosa copper
      protein were ineffective as electron donors for hydroxylamine reduction whereas
      reduced pyocyanine and methylene blue acted as electron mediators.

PMID- 19396991
TI  - A light-initiated, dark oxidation of bacteriochlorophyll from reaction center
      particles.
AB  - When reaction center particles from Rhodopseudomonas spheroides strain R26 are
      illuminated and then extracted with methanol, about one-third of the extracted
      bacteriochlorophyll slowly becomes oxidized, The oxidation does not occur under
      anaerobic conditions or in the absence of the detergent lauryldimethylamine
      oxide. Alkaline conditions also prevent the reaction. A dark interval between
      illumination and extraction delays the onset of bacteriochlorophyll oxidation in
      a predictable way. These results are consistent with the hypothesis that
      illumination generates a reaction initiator which is fairly stable in methanol
      but decays with a half-life of about 4.5 min in reaction center particles after
      illumination ceases.

PMID- 19396992
TI  - The relationship between delayed fluorescence and the carotenoid shift in
      chromatophores from Rhodopseudomonas capsulata.
AB  - (1) The kinetics of the change in intensity of 1-ms delayed fluorescence
      following the onset of illumination have been studied in chromatophores of
      Rhodopseudomonas capsulata and compared with the kinetics of the light-induced
      carotenoid shift, and of the change in fluorescence yield. The change in
      intensity of delayed fluorescence, when plotted on a logarithmic scale, followed
      closely the kinetics of carotenoid change, but not the change in fluorescence
      yield. (2) The antibiotics valinomycin, nigericin and antimycin, showed
      qualitatively similar effects on delayed fluorescence and the carotenoid shift,
      but the effects on fluorescence yield were quite dissimilar. (3) The extent of
      the carotenoid shift, induced by KCl pulses in the presence of valinomycin was
      used to calibrate the change as an indicator of membrane potential. The action of
      nigericin on both carotenoid shift and delayed fluorescence was used to relate
      the two, and a linear relationship was demonstrated between the logarithm of the
      intensity of the delayed fluorescence and the extent of the carotenoid shift.
      This relationship indicated that the intensity of delayed fluorescence was
      proportional to the exponential of the membrane potential. (4) It is suggested
      that the electrical component of the transmembrane electrochemical H+ gradient
      directly lowers the activation energy for emission, but that the pH component has
      no such effect.

PMID- 19396993
TI  - Time course of microsecond-delayed light emission from Scenedesmus obliquus.
AB  - The time course of microsecond-delayed light emission and that of prompt
      fluorescence was measured during the period of light adaptation for the wild-type
      strain and mutants Nos 8 and 11 of Scenedesmus obliquus, Strain D3, exposed t
      stimulus light in a photon-counting apparatus. As compared to prompt
      fluorescence, the delayed light emission was generally more susceptible to change
      in experimental conditions. (1) Illuminating normally grown wild-type cells with
      higher light intensities (100 mW/cm2 or higher), the intensity of delayed light
      increases to a maximum in th first few minutes, then decreases to a steady-state
      level after about 1 h. The maximu is missing at lower exciting light intensities.
      (2) Illuminating dark-adapted wild-type cells with high light intensities, the
      time course of delayed light emission is similar to that one described above,
      apart from a lag period within the very first minutes of light adaptation. That
      lag period is characterized by a relative minimum of the intensity lying higher
      than the intensity of the steady-state level. The length and the profile of the
      lag period depends on the time of dark adaptation. With increasing dark
      adaptation time the maximum of delayed light intensity appears later. (3) This
      maximum of delayed light intensity is only present for times shorter than 100 ps
      after turning off the stimulus light. (4) For mutant No. 8 the intensity of
      delayed light shows a steady decrease during the time course. (5) For light
      adapted wild-type cells the intensity of delayed light and that of prompt
      fluorescence increases linearly with increasing intensity of exciting light below
      the saturation point in the light curve (about 10 mW/cm2). The increase is less
      than linear above the saturation point. The results are discussed in terms of two
      photosystems coupled by an electron transfer chain.

PMID- 19396994
TI  - The electric generator in photosynthesis of green plants. I. Vectorial and
      protolytic properties of the electron transport chain.
AB  - Light induces the generation of an electrochemical potential difference across
      the functional membrane of photosynthesis of green plants. Experimental results
      on the electrochemical phenomena have been largely interpreted in terms of a
      vectorial alternating electron hydrogen transport system as originally
      hypothesized by Mitchell. We asked whether or not the reaction coordinate of the
      electron transport crosses the membrane, and whether or not the protolytic
      reactions at either side of the membrane can be understood from the protolytic
      properties of the redox components involved. For this we studied the flash-light
      induced protolytic reactions in the outer and the inner aqueous phase of the
      chloroplast inner disk membranes. Four sites of protolytic reactions were
      identified, two at either side of the membrane. One of these sites had to be
      attributed to the reduction of the terminal electron acceptor at the outer side
      of the membrane. Evidence is presented for the coupling of the other sites to the
      oxidation of water at the inner side of the membrane, to the reduction of
      plastoquinone at the outer side and its oxidation at the inner side,
      respectively. These results support Mitchell's hypothesis for the generation of
      an electrochemical potential difference by a vectorial electron transport system.

PMID- 19396995
TI  - Light-induced changes of C-550 and fluorescence yield in ultraviolet-irradiated
      chloroplasts at room temperature.
AB  - Effects of ultraviolet irradiation of chloroplasts on several photochemical
      reactions mediated by Photosystem II were studied at room temperature. The Hill
      activity and fluorescence of variable yield were decreased by ultraviolet
      irradiation in parallel. The activity of 2,6-dichlorophenolindophenol (DCIP)
      photoreduction in irradiated chloroplasts was only slightly recovered by addition
      of diphenylcarbazide, an electron donor for Photosystem II. No restoration of the
      original fluorescence yield was observed on addition of 3-(3,4-dichlorophenyl)
      1,1-dimethylurea (DCMU) or preincubating the irradiated chloroplasts with
      dithionite. Photobleaching of C-550 was much more resistant than the Hill
      activity or fluorescence of variable yield toward ultraviolet irradiation.
      Chloroplasts, of which the Hill activity and variable fluorescence had mostly
      been eliminated by ultraviolet irradiation, still showed C-550 photobleaching,
      which was in magnitude more than 50% of that in the original unirradiated
      chloroplasts. C-550 was shown not to respond to membrane potential. The
      photobleaching of C-550 is sensitized by Photosystem II and proceeds with
      unaltered quantum efficiency in ultraviolet-irradiated chloroplasts. These
      observations are interpreted to indicate that C-550 is not identical with Q, the
      hypothetical quencher of fluorescence, and that C-550 is a better indicator for
      the primary photoact in Photosystem II than Q.

PMID- 19396996
TI  - Charge accumulation at the reducing side of system 2 of photosynthesis.
AB  - A study was made of the reactions between the primary and secondary electron
      acceptors of Photosystem 2 by measurements of the increase of chlorophyll
      fluorescence induced in darkness by dithionite or by 3-(3,4-dichlorophenyl)-1,1
      dimethylurea (DCMU). The experiments were done either with chloroplasts to which
      hydroxylamine or carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP) was
      added, or with chloroplasts treated with tris(hydroxymethyl)aminomethane (Tris)
      to which phenylenediamine and ascorbate were added as donor system. Under these
      conditions the fluorescence increase induced by dithionite or DCMU added after
      illumination with short light flashes was dependent on the flash number with a
      periodicity of two; it was large after an uneven number of flashes, and small
      after a long darktime or after an even number of flashes. The results are
      interpreted in terms of a model which involves a hypothetical electron carrier
      situated between Q and plastoquinone; this electron carrier is thought to
      equilibrate with plastoquinone in a two-electron transfer reaction; the results
      obtained with DCMU are explained by assuming that its midpoint potential is
      lowered by this inhibitor.

PMID- 19396997
TI  - The action of tetraphenylboron as a system II electron donor and its effect on
      the decay of the electrical field across the thylakoid membrane.
AB  - The effect of tetraphenylboron on the O2 evolution, the electron transport in
      normal and in Tris-washed chloroplasts, and on the decay of the electrical field
      across the thylakoid membrane has been investigated in spinach chloroplasts. It
      was found that: (1) The average O2 yield per flash as a function of the
      tetraphenylboron concentration is dependent on the number of excitation flashes.
      With increasing flash number, the tetraphenylboron concentration which is
      required for 50% suppression of the average O2 yield per flash shifts toward
      higher values. (2) After the irreversible consumption of tetraphenylboron by
      System II oxidizing equivalents, the O2 evolution reappears. (3) The electron
      flow from System II to System I, as indicated by the amplitude of the reduction
      kinetics of the 703 nm absorption change, remains unaffected in the
      tetraphenylboron concentration range and at flash numbers where the O2 evolution
      is totally suppressed. (4) Tetraphenylboron restores electron transport in Tris
      washed chloroplasts. This tetraphenylboron-mediated electron transport is
      completely blocked by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). (5)
      Preliminary titration experiments favor the assumption that tetraphenylboron acts
      in chloroplasts rather as a 1-electron donor than as a 2-electron donor. (6)
      Tetraphenylboron accelerates the decay of the electrical field across the
      thylakoid membrane. Because of its ability to act as a System II electron donor,
      the accelerating effect on the electrical field is transitory if System II is
      active. By contrast, in DCMU-blocked chloroplasts with active System I electron
      transport [mediated by the 2,6-dichlorophenolindophenol (DCIP) cycle], a
      permanent accelerating effect on the electrical field is observed. From these
      results it has been concluded, that tetraphenylboron acts as an efficient 1
      electron donor for System II. The functional integrity of the water-splitting
      enzyme system Y is not required for this donation. Tetraphenylboron itself does
      not destroy the O2 evolution capability of chloroplasts, it rather acts as a
      competitive electron donor. However, an inhibitory effect arises probably from
      the oxidation products of tetraphenylboron. The possible modes of action of
      tetraphenylboron are discussed.

PMID- 19396998
TI  - Mechanism of activation and spectral shift of the F-695 emission band in
      chloroplasts as induced by 1,10-phenanthroline.
AB  - (1) Changes in the fluorescence emission spectrum of chloroplast, at 77 degrees
      K, induced by chaotropic reagents and 1,10-phenanthroline, were analyzed. (2)
      Fourth-derivative analysis of the emission spectra identified the exact location
      of a new band (referred to as "F-700") at 700 nm and showed that the conversion
      of F-695 into F-700 does not occur by a gradual red-shift of the F-695 band, but
      by the appearance of a new band at 700 nm at the expense of an intensity decrease
      in the F-695 emission. (3) F-700 shows two distinct fluorescence characteristics,
      namely the wavelength of its emission maximum and its intensity, but still
      retains the principal properties of F-695 such as steep temperature dependence at
      low temperatures, transient phenomena at 77 degrees K, and an excitation spectrum
      of the Photosystem II type. Thus F-700 is concluded to be a modified state of F
      695. (4) In addition to the compounds of the urea-guanidine class, inorganic
      anions such as SCN-, I- and CIO4- were active in the transformation. The
      specificity and theorder of effectiveness of these reagents indicated that their
      action is that of chaotropic reagents. Transformation was inhibited by the
      presence of compounds such as sugars, salts, alcohols and dimethylsulfoxide which
      seem to affect the activity of water. (5) 5-Methyl-1,10-phenanthroline partly
      substituted for the action of 1,10-phenanthroline, while the other six different
      derivatives of 1,10-phenanthroline and a few other bifunctional ligands were
      inactive. The structure-activity relations and the effective concentrations in
      the transformation differed greatly from those of the inhibition of the electron
      transport chain, suggesting that the action of 1,10-phenanthroline in the
      transformation is a yet unrecognized action of this reagent on Photosystem II.
      (6) Transformation was generally observed in chloroplast preparations from 11
      different higher plants and two species of algae tested. In Lolium sp. the
      transformation was partly attained by 1,10-phenanthroline alone. (7) From these
      results, the state of F-695 in chloroplast membranes and the mechanism of
      transformation into F-700 are discussed.

PMID- 19396999
TI  - Action of some derivatives of 1,10-phenanthroline on electron transport in
      chloroplasts.
AB  - The effectiveness and the mode of inhibitory action of some derivatives of 1,10
      phenanthroline and a few other substances on 2,6-dichlorophenolindophenol (DCIP)
      photoreduction and fluorescence induction at room temperature in spinach
      chloroplasts were compared in this paper. 4,7-Dimethyl-1,10-phenanthroline was
      the most potent inhibitor [pI50 (-log10 of molar concentration of inhibitor
      giving 50% inhibition), 5.9] examined, and 5-methyl-1,10-phenanthroline (pI50,
      4.2) was as potent as 1,10-phenanthroline (pI50, 4.4), in the case of DCIP
      photoreduction. The order of inhibition by 4,7-dimethyl-1,10-phenanthroline (n=2)
      was different from that of 1,10-phenanthroline and 5-methyl-1,10-phenanthroline
      (n=1), under the experimental conditions used. Fluorescence induction was
      diminished by 4,7-dimethyl-1,10-phenanthroline or 5-methyl-1,10-phenanthroline
      with the same pattern as 1,10-phenanthroline, but the effective concentrations
      varied corresponding to the pI50 values for the inhibition of DCIP
      photoreduction. Metal ions which form a chelate complex with phenanthroline of
      high stability constant prevented the inhibition of both DCIP photoreduction and
      fluorescence induction. From these results, the structure-activity relations and
      the mode of inhibition of the photosynthetic electron transport chain by these
      reagents are discussed.

PMID- 19397000
TI  - Inhibition of photosynthesis in isolated spinach chloroplasts by inorganic
      phosphate or inorganic pyrophosphatase in the presence of pyrophosphate and
      magnesium ions.
AB  - Inhibition of photosynthesis in isolated spinach chloroplasts by Pi is decreased
      by the presence of PPi and increased with increasing Mg2+ concentration.
      Previously reported regulation of this photosynthesis by protein factors from
      spinach leaves appears to be due mostly to pyrophosphate phosphohydrolase (EC
      3.6.1.1) activity which converts PPi to Pi and to the effects of PPi and Mg2+ on
      this pyrophosphatase activity.

PMID- 19397001
TI  - Alkaloids as inhibitors of photophosphorylation in spinach chloroplasts.
AB  - A group of 12 alkaloids were tested as inhibitors of photophosphorylation in
      spinach chloroplasts. Ajmaline, a dihydroindole alkaloid, was found to be the
      strongest inhibitor of both cyclic and non-cyclic photophosphorylation. Low
      concentrations of ajmaline also inhibited the dark and light ATPases, and the
      coupled electron flow from water to ferricyanide, measured either as ferrocyanide
      formed or as oxygen evolved, but not the uncoupled electron transport or the pH
      rise of illuminated unbuffered suspensions of chloroplasts. Higher concentrations
      of ajmaline stimulated, instead of inhibiting, photosynthetic electron transport
      or oxygen evolution and decreased the pH rise, thus behaving as an uncoupler,
      such as ammonia. Photophosphorylation was partially inhibited by 100 microM
      dihydrosanguinarine, 100 microM dihydrochelerythrine (benzophenanthridine
      alkaloids); 500 microM O,O'-dimethylmagnoflorine, 500 microM N-methylcorydine
      (aporphine alkaloids) and 1 mM julocrotine. They also inhibited coupled oxygen
      evolution and only partially (dihydrosanguinarine and dihydrochelerythrine) or
      not at all (the other alkaloids) uncoupled oxygen evolution. Spegazzinine
      (dihydroindole alkaloid), magnoflorine, N-methylisocorydine, coryneine (aporphine
      alkaloids), candicine and ribalinium chloride were without effect on
      photophosphorylation at 500 microM.

PMID- 19397002
TI  - Studies on cephalopod rhodopsin conformational changes in chromophore and protein
      during the photoregeneration process.
AB  - The ultraviolet absorbance of squid and octopus rhodopsin changes reversibly at
      234 nm and near 280 nm in the interconversion of rhodopsin and metarhodopsin. The
      absorbance change near 280 nm is ascribed to both protein and chromophore parts.
      Rhodopsin is photoregenerated from metarhodopsin via an intermediate, P380, on
      irradiation with yellow light (lamda >520 nm). The ultraviolet absorbance
      decreases in the change from rhodopsin to metarhodopsin and recovers in two
      steps; mostly in the process from metarhodopsin to P380 and to a lesser extent in
      the process from P380 to rhodopsin. P380 has a circular dichroism (CD) band at
      380 nm and its magnitude is the same order as that of rhodopsin. Thus it is
      considered that the molecular structure of P380 is close to that of rhodopsin and
      that the chromophore is fixed to opsin as in rhodopsin. In the change from
      metarhodopsin to P380, the chromophore is isomerized from the all-trans to the 11
      cis form, and the conformation of opsin changes to fit 11-cis retinal. In the
      change from P380 to rhodopsin, a small change in the conformation of the protein
      part and the protonation of the Schiff base, the primary retinal-opsin link,
      occur.

PMID- 19397003
TI  - Possible uncoupling of the mechanochemical process in the actomyosin system by
      covalent crosslinking of F-actin.
AB  - It has been speculated that F-actin depolymerizes during muscle contraction. In
      order to test this speculation, G-actin in F-actins were immobilized by
      crosslinking. While this did not affect activation of myosin ATPase,
      superprecipitation could be abolished. Sedimentation, light scattering, electron
      microscope, electrophoresis and homodyne spectra measurements seem to indicate
      that the average size of crosslinked segments increases with time of treatment
      with the crosslinking agent. At the same time, the amounts of dimers and trimers
      decreased. It appears that crosslinking makes F-actin filaments less flexible.
      The possible reasons for the loss of the capability to exhibit superprecipitation
      are discussed.

PMID- 19397004
TI  - [Cellular mechanisms of regulation of the inflammatory response in
      atherosclerosis: the role of cell contact-mediated signaling].
AB  - The regulatory mechanisms of the inflammatory process in the atherosclerotic
      plaque are still not clearly understood. Stimulated T cells may have a key role
      in enhancing and perpetuating inflammation at the atherosclerotic site. They
      activate endothelial cells, macrophages and smooth muscle cells in the
      atherosclerotic plaque, not only via the production of soluble mediators, but
      also through cell-cell contact-mediated interactions (via membrane receptors and
      their ligands). Cell/cell contact between stimulated T lymphocytes and
      monocytes/macrophages and endothelial cells induces the production of pro
      inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) and
      chemokines (interleukin-8, monocyte chemotactic factor-1). Thus, these
      interactions could play a relevant role in the disregulation of the inflammatory
      process in the atherosclerotic plaque, representing a novel mechanism of
      progression and complication of the atherosclerotic disease. Understanding the
      key ligands and receptors involved may permit the definition of new therapeutic
      targets.

PMID- 19397005
TI  - [Non-pharmacological, non-conventional therapy of chronic refractory angina
      pectoris].
AB  - Chronic refractory angina pectoris is a clinical entity characterized by a
      persistent thoracic pain, despite pharmacological therapy (Canadian
      Cardiovascular Society functional class 3-4); the patients show a severe, diffuse
      coronary atherosclerosis not amenable to myocardial revascularization at coronary
      angioplasty or bypass grafting. This clinical entity which is becoming ever more
      frequent is a cause of a poor quality of life necessitating repeated
      hospitalization. Many therapeutic alternatives have been proposed for the
      treatment of these patients, but results were inconclusive. In this review their
      pathophysiological background, clinical efficacy, safety and complications are
      analyzed. Data concerning spinal cord stimulation, upper thoracic sympathectomy,
      high thoracic epidural analgesia, chronic-intermittent urokinase administration,
      enhanced external counterpulsation and transmyocardial laser revascularization
      are presented. Finally, the main research directions in this particular field are
      reported.

PMID- 19397006
TI  - [Cardiovascular risk stratification. Systolic, diastolic or pulse pressure?].
AB  - It is well known that hypertension is a highly prevalent condition in the
      population, carries a significant risk of adverse cardiovascular events and is
      therapeutically difficult to control. These factors render it "a major unsolved -
      but soluble - mass public health problem". One of the present-day aspects of the
      complexity of managing patients with high blood pressure (BP) derives from
      clinical and epidemiological data that have emerged over the past 10 years: the
      growing importance of the clinical significance of systolic and pulse BP. The
      pathophysiological basis of these data is based, on the one hand, on a better
      articulated definition of the components of BP, and on the other, on precise
      information concerning age-related modifications. The common definition of BP
      does not take into account pressure fluctuations occurring during the cardiac
      cycle; in fact, systolic and diastolic BP denote the extreme values of continuous
      variations in differential pressure. Diastolic BP reflects, to a greater extent,
      the trend of arterial resistances and mean BP (usually calculated as diastolic BP
      plus one third of the differential BP, and considered the "stable component" of
      the arterial sphygmogram) and has long been used as a diagnostic and therapeutic
      target. Systolic BP is more closely linked to variations in pulse BP (given from
      the difference between systolic and diastolic BP and considered the "dynamic
      component" of the arterial sphygmogram) and is produced by a group of factors
      including left ventricular ejection and the reflection of the sphygmic wave. As
      age increases, the walls of the aorta and the large elastic arteries
      progressively harden due to senile degenerative phenomena and the loss of
      elasticity as well as the progressive diffusion of atherosdclerotic lesions. This
      leads to the reduced capacity of the arterial wall to distend during the systole
      with a consequent increase in both systolic and pulse BP. These
      pathophysiological data have important clinical and prognostic implications and
      account for the possible diversity of significance to attribute to systolic,
      diastolic, mean and pulse BP, factors which, in their entirety, can represent an
      element, albeit partial, of resolvability of problems in managing hypertension.
      In fact, possibilities of diversification in the stratification of risk of the
      hypertensive patients may be considered on a pathophysiological basis, with the
      prospect of better aimed therapeutic interventions. On the whole, it appears that
      the clinical significance to attribute to pulse BP should be considered not as an
      alternative to that of systolic and diastolic BP, but rather in complementary
      terms, with age kept in careful consideration. In practice, by simplifying to a
      maximum the state of present knowledge, the values of systolic, diastolic, mean
      and pulse BP are all important in subjects under 60 years old. This indicates
      that the clinical significance to attribute to diastolic hypertension in young or
      middle-aged patients, which have been so accurately described by well-known meta
      analyses, is not presently under discussion. What seems to change, with respect
      to the past, is the importance that should be attributed to the systolic and
      pulse BP in subjects of all ages and in particular to pulse BP in subjects over
      60 years old: in these persons, the increase in pulse BP summarizes and
      integrates the adverse prognostic value of an elevated systolic BP and a low
      diastolic BP. It should be clearly understood that, in subjects over 60 years
      old, a high systolic BP and a low diastolic BP mean rigidity of the wall of the
      aorta and of the main elastic arteries; in these subjects, the isolated increase
      in diastolic BP, usually easily controllable by antihypertensive treatment,
      should not cause excessive clinical concern; instead, an increase in systolic BP 
      even if isolated - and, above all, an increase in pulse BP, should cause greater
      preoccupation, inasmuch as they are signs of consistent serious structural
      lesions. In other words, a 60-year-old subject with 150/90 mmHg would have a
      lesser risk of cardiovascular events, particularly cardiological events, than a
      contemporary with equal risk factors who has 150/50 mmHg. A large number of
      clinical studies suggest that an increase in pulse BP seems to predict cardiac
      ischemic events to a greater extent than the cerebrovascular events, which seem
      to be predicted to a greater extent by the mean BP. On the therapeutic level, the
      reference datum is represented by the unequivocal demonstration, furnished by
      wide scale interventional studies, that in hypertensive patients adequate
      pharmacological control of both the diastolic and systolic BP, particularly in
      the elderly, significantly reduces adverse consequences linked to the progression
      of atherosclerotic disease in the heart, brain and kidney. A degree of complexity
      is represented by the modest percent of patients in treatment who have BP values
      < 140/90 mmHg. Only a series of ad hoc studies will enable us to know when and if
      this negative situation can be resolved, even partially, by the clinical
      application of new knowledge in the pathophysiological field. From this point of
      view, it should be kept in mind that ACE-inhibitors, diuretics, dihydropyridinic
      calcium antagonists and vasopeptidase inhibitors seem to be more effective than
      beta-blockers in terms of preferential reduction of pulse BP. The contents of the
      reports that make up the Symposium constitute a valid base of knowledge and
      represent a concrete stimulus for research initiatives, which in the spirit of
      "operativeness" of the Area Prevenzione of the Italian Association of Hospital
      Cardiologists, follow the objective of bringing together scientific and
      managerial needs.

PMID- 19397007
TI  - [Systolic, diastolic and pulse pressure: pathophysiology].
AB  - Arterial hypertension is the result of abnormal flow/resistance relationships.
      Resistance to outflow consists of different components: the systolic component is
      the one generated by conductance vessels, whereas the diastolic component
      consists of peripheral resistance, which regulates peripheral blood supply due to
      the run-off of conductance vessels during left ventricular diastole. Thus, an
      increase in systemic resistance results in a rise in diastolic blood pressure. If
      the elasticity of conductance vessels decreases, diastolic run-off also decreases
      and diastolic blood pressure goes down. When this loss of elasticity occurs, the
      ejection force cannot be anymore offset by arterial distension, the pulse wave
      velocity increases and reflex waves to the heart arrive earlier, causing the
      systolic blood pressure to augment. Such an augmentation, together with
      decreasing diastolic blood pressure results in an enhancement of the pulse
      pressure. When the stroke volume is normal, an increase in pulse pressure is,
      therefore, a marker of altered conductance. However, if, due to loss of
      elasticity of the conductance arteries diastolic blood pressure goes down,
      increasing systolic pressure also protects against a decrease in mean pressure.
      Indeed, in conditions of elevated pulse pressure, the mean pressure can be normal
      or high, indicating that when evaluating blood pressure all components should be
      taken into consideration. A high systolic blood pressure associated with a normal
      mean blood pressure is suggestive of a normal peripheral resistance. In this
      context, isolated systolic hypertension can be conveniently divided into a normal
      peripheral resistance type, and into a high peripheral resistance type when it is
      associated with high values of mean blood pressure (independently of whether or
      not the diastolic blood pressure is increased). In this latter occurrence, a high
      pulse pressure is more likely to be a marker of severe target organ damage
      (conductance arteries) than of a direct causal risk factor such as systolic blood
      pressure.

PMID- 19397008
TI  - [Blood pressure components and target organ damage].
AB  - In a given hypertensive patient, clinically overt cardiovascular disease is often
      preceded by a number of signs of target organ damage at the cardiac, arterial and
      renal levels. These changes have been collectively defined "pre-clinical
      cardiovascular disease", and carry a substantially increased risk for future
      cardiovascular complications. The present article examines the relationship
      between blood pressure components and target organ damage in essential
      hypertension. Arterial pressure can be split into a steady component (represented
      by the mean arterial pressure), which is a measure of the average level of
      pressure in a given artery, and a pulsatile component (represented by the pulse
      pressure), which estimates the cyclic oscillations around the mean. All blood
      pressure components show a positive, linear correlation with left ventricular
      mass, both in the general population and in patients with essential hypertension.
      However, the association is significantly stronger for the steady blood pressure
      components (systolic and mean arterial pressure) than for the pulse pressure.
      Available data regarding arterial changes suggest that the association is partly
      different. The majority of available studies show that large-artery intima-media
      thickening and discrete atherosclerotic plaques are better predicted by pulse
      pressure than by other blood pressure components, particularly in the elderly.
      After the age of 60, there is clear-cut evidence for a J-shaped relationship
      between diastolic blood pressure and arterial thickening or plaques, while for
      younger age groups the relationship appears to be linear. These data might offer
      an explanation for the observed superior prognostic value of pulse pressure in
      the elderly. The relationship between the different blood pressure components and
      renal damage is more controversial. In summary, pulsatile, cyclic stress (as
      represented by pulse pressure) appears to be more important in determining
      arterial changes in hypertensive patients, while steady blood pressure components
      play a dominant role in the development of hypertensive left ventricular
      hypertrophy.

PMID- 19397009
TI  - [Systolic, diastolic and pulse pressure: prognostic implications].
AB  - Over the past decades, diastolic blood pressure (BP) has been traditionally
      considered superior to systolic BP for cardiovascular risk stratification.
      However, the Framingham Heart Study, the Physicians' Health Study and several
      other studies published over the last few years, provided convincing evidence
      that pulse pressure (i.e., the difference between systolic and diastolic BP) is
      the most important BP component for prediction of cardiovascular risk,
      particularly in subjects over 55 years of age. Evidence is accumulating that
      pulse pressure is a powerful predictor of cardiovascular risk in different
      clinical settings including the general population, elderly subjects, patients
      with essential hypertension and patients with systolic dysfunction. Elevated
      pulse pressure may be considered a reliable marker of stiff arteries, possibly
      due to diffuse atherosclerotic lesions, aging processes of the artery wall and
      other mechanisms. Brachial pulse pressure, however, might not be a reliable
      marker of central pulse pressure because of the progressive amplification of the
      pressure wave from the aorta to the peripheral arteries, a phenomenon which tends
      to decrease with age and to increase with height. Since the state of increased
      emotional stress associated with physical examination leads to a bigger rise in
      systolic than in diastolic BP, the clinical visit may lead to an overestimation
      of the usual levels of pulse pressure. In fact, ambulatory pulse pressure proved
      to be more potent than office pulse pressure for cardiovascular risk
      stratification. An average 24-hour ambulatory pulse pressure >53 mmHg identifies
      subjects with a markedly increased cardiovascular risk. An increase in pulse
      pressure apparently predicts cardiac ischemic events better than cerebrovascular
      events. On the other hand, the latter are better predicted by the mean BP. The
      effects of antihypertensive drugs and drug combinations on the mean BP and pulse
      pressure, and the potential prognostic implications, deserve further evaluation.

PMID- 19397010
TI  - [Systolic, diastolic and pulse pressure: therapeutic options].
AB  - It is now universally accepted that antihypertensive therapy reduces
      cardiovascular morbidity and mortality both in young and older patients. The
      clinical relevance of the systolic, diastolic and pulse pressure as independent
      risk factors is well recognized. The reduction of cardiovascular morbidity and
      mortality in hypertensive patients is the main therapeutic goal. There is
      substantial agreement on the treatment of individual risk factors and associated
      clinical conditions, but the best drug therapy for systolic and diastolic
      hypertension and/or high pulse pressure is still controversial. The
      recommendations of the JNC VI are that diuretics or beta-blockers be used as
      first-step drug therapies. The WHO-ISH guidelines recognize calcium antagonists,
      ACE-inhibitors, alpha-blockers and angiotensin II receptor antagonists as first
      step drug therapies together with diuretics and beta-blockers. All these drugs
      have a similar hypotensive potential and reduce cardiovascular risk, but with
      noticeable differences in tolerability and side effects. It has long been
      demonstrated that diuretics and beta-blockers significantly reduce the
      cardiovascular risk, but their side effects can be relevant. ACE-inhibitors have
      proved to be efficacious in hypertensive patients with chronic heart failure and
      diabetes. Calcium antagonists are useful in the prevention of stroke but results
      in patients at high risk of coronary artery disease and heart failure are
      controversial. Alpha-blockers have proved to be unsafe in patients with heart
      failure but showed beneficial effects in young patients with diastolic
      hypertension. Angiotensin II receptor antagonists have proved to be safe and
      efficient but their advantages in comparison to other drugs need to be confirmed.

PMID- 19397011
TI  - [Forensic medicine aspects in patients with chest pain in the emergency room].
AB  - The correct management of patients presenting with chest pain in the emergency
      room is, at the moment, a very peculiar and controversial issue. A rapid
      confirmation or exclusion is imperative for the respect of the health of citizens
      and the reduction of public expenditure. The concept of professional fault is
      defined and the previous and present behavior of the magistrature are debated as
      regards the faults of physicians. Some practical suggestions conclude this
      review.

PMID- 19397012
TI  - [The genetic area of the Italian Association of Hospital Cardiologists. The
      family history in modern cardiology--part I].
AB  - The family history constitutes the first step in the cardiologist's clinical
      approach to the patient and is highly informative both for monogenic and
      multifactorial disorders. A detailed interview is a time-consuming activity: in
      their daily practice, cardiologists may have 10, 20 or more interviews to
      complete. The patient tends to concentrate his attention on his own clinical
      history, rather than on that of his family, and explaining the importance of the
      role of a well analyzed family history in the modern cardiology can be difficult
      and may further increase the loss of time. However, the information about a given
      phenotype revealed by a detailed and non-confounding family history is essential
      to define the inheritance of monogenic diseases, to calculate the penetrance,
      even when the disease genes are unknown, or to evaluate "clinically cryptic"
      risks in multifactorial diseases. The Genetic Area of the Italian Association of
      Hospital Cardiologists proposes a novel approach to the family history of the
      patients: a guide form to be filled in by the patient whilst awaiting for
      clinical evaluation or immediately after admission to the cardiology department.
      The proposal will be articulated in three parts: one dedicated to general
      considerations on the confounding or incomplete evaluation of potentially useful
      data from the family history, one specifically dedicated to cardiomyopathies, and
      one containing a model of the form to be eventually adopted by the cardiological
      scientific societies.

PMID- 19397013
TI  - [The SCOOP II trial in heart failure].
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of a health
      education intervention aimed at improving therapeutic compliance and quality of
      life of patients with chronic heart failure (CHF). In this 1100 bed Community
      hospital 97% of patients with CHF admitted to the Internal Medicine Unit have a
      high rate of readmission, mortality and negative quality of life. METHODS: Two
      hundred patients (123 males, 77 females, mean age 75 years) were enrolled and
      randomized. CHF patients admitted to the Internal Medicine Unit were randomly
      assigned to usual care (n=100) or intervention group (n=100), which consisted of
      a nurse-guided education program, facilitated telephone communication and
      regularly scheduled follow-up visits with an internist. The primary endpoints
      were quality of life and quality of service improvement, and improved compliance
      with the heart failure guidelines. All patients were submitted to
      echocardiography. RESULTS: Ejection fraction is available for 87% of them.
      Baseline quality of life is similar in both groups. Final data will be available
      after April 2001.

PMID- 19397014
TI  - [Epicardial ablation of atrial fibrillation during heart valve surgery].
AB  - BACKGROUND: We report the results of an intraoperative ablation procedure for
      combined treatment of atrial fibrillation (AF) in patients affected by heart
      valve disease. METHODS: From February 1998 to June 2000, 80 patients scheduled
      for heart valve operations underwent combined surgical treatment of AF. Seventy
      eight patients had mitral valve disease and 2 had aortic regurgitation; 74
      patients were affected by chronic AF (mean 50 +/- 74 months, range 6-480 months)
      and 6 had paroxysmal AF. A left atrial set of radiofrequency ablations (mainly
      epicardial) was performed in all patients. RESULTS: Thirty-five patients
      underwent conservative mitral valve surgery, 43 had mitral valve replacement and
      2 had aortic valve replacement. The combination of the ablation procedure did not
      lead to a substantial prolongation of cardiopulmonary and aortic cross clamp time
      and did not increase perioperative morbidity. No procedure-related complications
      were recorded. Operative mortality was favorably comparable with that of valvular
      surgery alone (2.5%). Mean hospital stay was 6.8 +/- 4.4 days. At follow-up (16.2
      +/- 9.2 months, range 3-28 months), 61 patients (78.2%) were in stable sinus
      rhythm; all of them recovered left and right atrial contractility as assessed by
      Doppler echocardiography. CONCLUSIONS: The combined treatment of AF with a
      radiofrequency ablation surgical technique is effective in restoring stable sinus
      rhythm and atrial contractility. The procedure is low risk thereby allowing a
      prompt clinical recovery after operation. It should therefore be considered in
      all patients with AF undergoing open-heart surgery.

PMID- 19397015
TI  - [Notes to the regulatory Appendix 13 of the Italian Committee for Drugs].
AB  - The Italian Committee for Drugs has recently modified "Appendix 13" to a recent
      Italian regulation related to reimbursement of hypolipidemic agents for primary
      or secondary prevention of heart diseases. There is some confusion in concepts,
      terminology and phrasing, also dealing with disease definition, which need
      comment. Moreover, "Appendix 13" suggests to estimate risk based on charts
      derived from the Framingham experience, which are inappropriate when applied to
      Italy. Finally, "Appendix 13" is not clear as to how categorize high risk
      individuals. There has been a growing interest in estimating coronary risk since
      1994, probably as the result of primary and, secondary intervention trials with
      statins used to lower blood cholesterol levels. On the other hand, European
      guidelines have been published, accompanied by risk charts (derived from the
      Framingham study) helping to index individuals who may benefit from treatment of
      coronary risk factors. At least thirteen such or similar instruments have been
      produced worldwide (and three of these in Italy) to estimate coronary risk. In
      Italy, there are other instruments in preparation. Data are reviewed wherefrom it
      is possible to conclude that it is inadequate, since substantially erroneous, to
      use risk functions to estimate absolute coronary risk when these are derived from
      largely different populations as to those in which practical applications are
      looked for.

PMID- 19397016
TI  - [New rules on hypolipidemic drug reimbursability in Italy].
AB  - The Italian National Committee for Drugs (CUF) has recently reviewed the
      reimbursement criteria for hypolipidemic drugs in our country. The new rules
      allow the reimbursement of statins and fibrates in patients with familial
      dyslipidemias, and of statins in hypercholesterolemic subjects who are not
      responders to an appropriate diet and are at high risk of a first major
      cardiovascular event, or already affected by coronary heart disease. To evaluate
      the level of coronary risk, the new document suggests to use risk algorithms or
      risk charts. The use of the risk charts recently published by the European
      Societies of Cardiology, Hypertension and of Atherosclerosis, and based on the
      Framingham algorithm, is suggested for risk grading of patients without
      clinically overt coronary heart disease. For coronary patients, the risk chart
      based on the follow-up of the cohort of the Italian GISSI-Prevenzione study
      should be used. Therefore, the reimbursement of statins will no longer be linked,
      according to this document, to cholesterol plasma levels, but rather to a
      specific level of coronary risk. By following these guidelines, the theoretical
      ground for a more appropriate use of these drugs, also characterized by a more
      favorable cost-benefit ratio, is established. Even if some aspects of the CUF
      document may need revision or clarification, it can be envisaged that it will
      favorably impact on the quality of cardiovascular prevention in our country.

PMID- 19397017
TI  - [Spontaneous dissection of the left main coronary artery: a case report and
      review of the literature].
AB  - Primary spontaneous coronary artery dissection occurs rarely. Compared to usual
      acute coronary syndromes, it occurs in relatively young people, particularly in
      women in the peripartum or early post-partum period. The etiology of spontaneous
      coronary artery dissection remains unclear; there have been less than 150 cases
      reported in the literature, and only 28 cases documented in the left main
      coronary artery. This article reports the clinical course of a patient with
      primary spontaneous left main coronary artery dissection who was treated with
      coronary artery bypass grafting after clinical steadiness.

PMID- 19397018
TI  - [Hematoma of right ventricular outflow tract mimicking an infiltrating tumor as a
      consequence of acute aortic dissection].
AB  - The aortic dissection may be associated with unusual complications such as
      fistula formation and vascular compression. We describe a case of a 71-year-old
      patient admitted to our Hospital because of acute chest pain; transthoracic and
      transesophageal echocardiography revealed the presence of a type A aortic
      dissection associated with a mass infiltrating the right ventricular outflow and
      proximal tract of the pulmonary artery. The ultrasonographic morphology and the
      surgical findings showed the presence of a hematoma which was consequent to acute
      aortic dissection and which mimicked a tumor infiltrating the right ventricular
      outflow.

PMID- 19397019
TI  - [The cardiologist and the limitations of reimbursement of statins].

PMID- 19397020
TI  - [The cardiologist and the limitations of reimbursement of statins].

PMID- 19397021
TI  - [The FRISC II study: is it justified to extend the invasive strategy to all
      patients with non-ST segment elevation acute coronary syndrome].

PMID- 19397022
TI  - [Carlos Chagas Filho's choice of biological physics: reason and motivations].
AB  - This study investigates the reasons and motivations behind Carlos Chagas Filho's
      choice to abandon the line of study developed by his father, Carlos Chagas, and
      brother, Evandro Chagas, both of whom had very successful careers researching
      tropical diseases. Though Carlos Chagas Filho first worked on anatomical
      pathology, he suddenly shifted his attentions of the physicochemical aspects of
      vital processes. Extant sources show that a number of unforeseen circumstances
      took place from early on in Chagas Filho's education. There was a chance he could
      carry out work of a similar import in a different area and he set his sights,
      with uncommon luck, on the introduction of scientific research at university.

PMID- 19397023
TI  - [The public perception of information about the potential risks of genetically
      modified crops in the food chain].
AB  - At a time when genetically modified (GM) crops are entering the Brazilian food
      chain, we present the findings of a study that makes use of a qualitative
      technique involving focal groups to look into the public's interpretation of the
      information available about this biotechnological innovation. This methodology
      produced results that revealed the interconnections drawn by the research
      subjects between this form of biotechnology, changes to the environment, and food
      production in general. The mistrust expressed about GM crops was particularly
      attributed by the participants to the non-availability of comprehensible
      information in the mass media or on product labels.

PMID- 19397024
TI  - [Government tutelage of mothers and children in Argentina: administrative
      structures, law, and technical staff (1936-1955)].
AB  - The article describes and analyzes one of the political projects that gained
      strength in Argentina during the between-war years and remained in place
      throughout Peronism: government tutelage of mothers and children. It examines how
      the Direccion de Maternidad e Infancia viewed the mother-child dyad, how this
      office proposed to address the issue of infant mortality, what type of technical
      staff was in place, and what limitations were encountered in trying to enforce
      these ideas. It also looks at what changed and what stayed the same at the office
      under Peronism.

PMID- 19397025
TI  - [Torrent of madmen: the language of degeneration in Portuguese psychiatry at the
      close of the 19th century].
AB  - The scope of this article is to show the importance of a highly naturalized model
      of human actions that, taking as its pivotal point a hereditary explanation, was
      widely used by Portuguese psychiatry at the close of the 19th century, in
      continuity with what was happening in the European context. 'Degeneration'was
      instituted as a species of based on which experiences were classified and
      described with occasionally threatening contours for a certain conception of the
      social and political order. Various phenomena, nosologically described in
      differentiated forms, came to be integrated into the language of degeneration.
      Its expansive and supposed metatheoretical character became involved in its death
      throes, coming to be progressively replaced by another model, psychoanalysis.

PMID- 19397026
TI  - [The suicide of slaves in Sao Paulo during the last two decades of slavery].
AB  - News stories printed in Gazeta de Campinas (1871-1887) are used to investigate
      the views expressed at the time of the suicides of captives and freedmen in Sao
      Paulo province, and to discuss the data available. As suicide is a form of human
      behavior which cannot be reduced to one single explanation, it does not seem
      justifiable that amongst the slaves, these cases should also be taken as self
      explanatory because of the conditions in which they occurred. By noting the
      circumstances in which these acts took place, it is hoped that the fallacy of
      oversimplified explanations can be belied, which refer to the suicide of slaves
      as quite simply being due to a 'dislike of captivity'.

PMID- 19397027
TI  - [Norbert Elias and a narrative about ageing and death].
AB  - This article investigates the contribution made by Norbert Elias (1897-1990) to
      the problematization of old age by analyzing his text "Envelhecer e morrer".
      Here, the sociologist is seen as an author of texts which can help build up
      references that span disciplinary boundaries, or even overcome the polarization
      between 'health-' and 'social-'related knowledge, making it possible to form the
      desired field of study on ageing. Though Elias sometimes aligns himself with
      ideas bordering on an idealization of ageing from a pre-capitalist 'Golden Age',
      he does offer insights which deserve to be taken into consideration, especially
      when he relates the contemporary experience of ageing to the invention of
      modernity itself.

PMID- 19397028
TI  - [Marina de Vasconcellos and the social sciences in Rio de Janeiro: a study of the
      social circles].
AB  - An investigation of the career of one of the "founding mothers" of the social
      sciences in Rio de Janeiro, Marina de Vasconcellos, successor of Arthur Ramos, is
      one way of understanding how anthropology was established in Rio de Janeiro.
      Conflicts and alliances, continuities and discontinuities, lie behind the
      pioneering Brazilian Society of Anthropology and Ethnology and the Institute of
      Social Sciences, both at Faculdade Nacional de Filosofia. Marina de Vasconcellos'
      professional life bore the marks of the clash between different schools of
      thought regarding anthropology at a time when university courses were being
      introduced. As a professor, she was committed to educating new professionals, and
      in 1968, she was steadfast in the struggle for university autonomy. The study
      leads to a reflection upon the criteria for success in academia, countering the
      view that this depends entirely on the publication of books and articles.

PMID- 19397029
TI  - [Institutionalization of the sciences, gender system, and scientific production
      in Brazi (1939-1969)].
AB  - Thanks to policies put in place in the 1930s, women's experiences in higher
      education increased their professional participation in the academic and
      scientific worlds. Largely neglected in Brazilian historiography of the sciences,
      analysis of this phenomenon introduces a new perspective on the meaning of
      institutionalization and professionalization of scientific activities, a process
      in which women have played an authentic role. We explore their presence by
      analyzing the scientific production published in four journals between 1939 and
      1969. Gender differences are detected according to the standard of the
      publication.

PMID- 19397030
TI  - [Prominence in the media, renown in the sciences: the construction of a
      paradigmatic feminist and a scientist at Rio de Janeiro's Museu Nacional].
AB  - Bertha Lutz was one of the women of her generation who enjoyed indisputable
      political and scientific authority. She wrote much and even more was written
      about her, especially during her day. The newspaper chronicles by Lima Barreto,
      countless letters, scientific papers, and unpublished texts by Bertha herself
      that are surveyed in this article indicate how much her feminism--inseparable
      from other dimensions of her life--fostered her professional career. Her feminism
      earned her a carefully constructed renown and visibility that interlocked with
      her professional performance. Science lent her social prestige and guaranteed
      legitimacy for her causes. During a period when the scientific community itself
      was engaged in publicizing its own activities, Bertha's feminist prominence in
      the media helped her make a name in the sciences.

PMID- 19397031
TI  - ['Young women and lady dentists': training, degrees, and the market in the first
      decades of the Republic].
AB  - Since the 1980s, more women than men have graduated from Brazil's dentistry
      schools, yet little has been written about women's access to the profession. This
      article provides background information useful in analyzing the training and
      professional roles of women dentists in Brazil during the first years of the
      Republic; discusses the relation between changes in the profession, health
      policies, and the gender system during that period; and contributes to the
      discussion on the feminization of the profession. The article is part of a
      broader project investigating training, professional roles, and the labor market
      in the health field in Sao Paulo. Sources include articles published in
      newspapers, magazines, and specialized journals devoted to dentistry, pharmacy,
      and medicine, along with government and university records covering the years
      1892 through 1926.

PMID- 19397032
TI  - [Women's presence in undergraduate and graduate courses: deconstructing the idea
      of university as a male domain].
AB  - Women's entrance into the university in recent Brazilian history is a sign of the
      changes underway in our society. The present analysis takes the slice of the
      population that holds a university diploma and contextualizes it within the
      broader process of boosting enrollment at Brazilian schools, while emphasizing
      continuities and ruptures in the pattern of male and female participation in this
      arena. Based on the last four IBGE censuses, our analysis reveals that in thirty
      short years women have managed to reverse a picture of historical inequality and
      to solidify a new reality in which they are the clear majority (60%) of college
      graduates in younger cohorts. A comparison between those holding university
      degrees in 1970 and in 2000 shows a significant entrance of women into
      traditionally male courses.

PMID- 19397033
TI  - [The reign of hormones and the construction of gender differences].
AB  - Within the context of the theoretical debate on gender and science, the article
      discusses the process of redefining gender and sex differences using so-called
      biological or natural markers. It identifies how gender differences undergo
      naturalization using a logic of 'substantialization or 'materialization'. This
      process is exemplified in how medicine views women, promoting explanatory models
      of economics of the female body that are at times centered around organs like the
      uterus and ovaries, at other times centered on the mechanics of hormones, and,
      most recently, focused on genetic and neurological differences. More
      specifically, it follows the discovery of so-called sex hormones and its relation
      to a dualist perspective of gender. These powerful chemical messengers helped
      shaped the passage from the logic of excess surrounding sex through the late
      nineteenth century, to the imperative of insufficiency, prevalent since the mid
      twentieth century.

PMID- 19397034
TI  - ['Being a mother is a science': women, physicians, and the construction of
      scientific maternity in the 1920's].
AB  - The article analyzes the construction of the notion of scientific maternity in
      Brazil in the 1920s as part of the broad republican reform project meant to build
      nationhood. With the active participation of women, multiple social agents were
      involved in configuring the maternalist discourse and in reshaping relations
      between women and doctors into a partnership negotiated around a mutual interest
      in valuing maternity. Special attention is paid to the essential role played by
      women's magazines in this process.

PMID- 19397035
TI  - [Forbidden sexualities: madness and the male gender].
AB  - The article identifies and studies male sexuality and affectivity as forbidden
      and imprisoned in Brazilian asylums in the first decades of the Republic. By
      analyzing psychiatric records from that era, it explores the notion that sexual
      and affective behavior had little to do with the construction of male profiles
      deemed 'deviant' and/or 'pathological'. This reflection shifts the focus of
      analysis to the gender specificities that determine the various traits displayed
      in 'mental disturbances' attributed to certain sexual and affective behavior.

PMID- 19397036
TI  - [Female images in O Vulgarizador: science's public and women in the nineteenth
      century].
AB  - The article examines images of women in the periodical O Vulgarizador, which
      sought to bring science into the public forum in nineteenth-century Brazil. An
      analysis of these images helps us recognize some of the issues of ongoing concern
      in the magazine: the United States as a model of progress and industrial
      development, the importance of World Fairs, and transformations in Brazilian
      society and women's role therein.

PMID- 19397037
TI  - [A road to science: the trajectory of the botanist Leda Dau].
AB  - This interview with Leda Dau explores her career at the Museu Nacional from 1953
      to 1994 and her dedication to research and teaching in the field of botany. She
      was a member of one of the first generations of women who felt the effects of the
      social transformations that began in the 1920s. This process brought changes to
      the gender system in Brazil and improved women's opportunities for schooling and
      professionalization, thereby allowing them access to the era's restricted world
      of science.

PMID- 19397038
TI  - Web med.

PMID- 19397039
TI  - The doctor is in (your inbox).

PMID- 19397040
TI  - Fix Minnesota's frayed health care safety net.

PMID- 19397041
TI  - MMA leaders: low pay threatens safety net.

PMID- 19397042
TI  - E-prescribing 101.

PMID- 19397043
TI  - Mixing it up.

PMID- 19397044
TI  - Tangled in technology.

PMID- 19397045
TI  - Medicine in the era of Web 2.0.

PMID- 19397046
TI  - Laptop learners.

PMID- 19397047
TI  - A blueprint for 21st century health care: requirements for standard, electronic
      administrative data.
AB  - Starting this year, health care providers and payers in Minnesota will be
      required to use a single set of data specifications to electronically exchange
      information about patients' eligibility for insurance coverage and benefits,
      submit and pay claims, and exchange and record payment remittance advice.
      Minnesota is the first state in the nation to require such electronic
      transactions, which could reduce administrative costs by more than $60 million a
      year. This article describes the 2007 law that led to this change, the
      transactions to which it applies, and the penalties for noncompliance.

PMID- 19397048
TI  - Describing the deficits in IADLs as functional impairment of Alzheimer's disease.
AB  - Assessing the deficits in instrumental activities of daily living (IADLs) may be
      pivotal in understanding Alzheimer's disease (AD). Yet, the assessment of
      functioning in AD is often related to deficits in activities of daily living
      (ADLs) and assessed after manifested objective cognitive deterioration and a
      diagnosis of AD. Therefore, the purpose of this longitudinal, descriptive,
      secondary analysis is to describe the deficits in IADLs in normal-functioning
      elders who develop AD and in persons with mild cognitive impairment (MCI) who
      develop AD within a 4-year period. The study will also describe the relationship
      between deficits of IADLs at baseline and the progression of AD at follow-up. The
      sample consisted of 41 community-residing White elders (mean age = 67 +/- 8).
      Measurements assessed the progression of AD from normal functioning to AD (the
      Global Deterioration Scale) and deficits in IADLs/ADLs (the Functional Assessment
      Staging of AD), in cognition (Mini Mental State Examination), and in memory
      skills (the Guild Memory Test and Wechsler Adult Intelligence Scale).
      Nonparametric statistics and cross-tabulation analysis were used with an alpha of
      .05. Deficits in IADLs differentiated normal-functioning persons from those with
      MCI (LR [2, N = 401 = 9.17, p < or = .01) associated with AD progression (CV =
      .57, p < or = .002), and differentiated the progression of normal-functioning
      elders to AD (p < or = .0001). Baseline deficits in IADLs approached significance
      in describing AD progression at follow-up (p < or = .09). Deficits in cognition
      and memory skills occurred later. Assessing deficits in IADLs may significantly
      enhance the understanding of AD for early assessment and treatment.

PMID- 19397049
TI  - Effects of parity on blood pressure among African-American women.
AB  - It is a well established fact that age, ethnicity, weight, and lifestyle
      behaviors can affect blood pressure (BP). Co-morbid conditions such as HELLP
      syndrome (hemolysis, elevated liver enzymes, and low platelets), pre-eclampsia,
      and previous hypertension diagnosis might also be risks for chronic hypertension
      among women who have had children. Although parity has been linked to changes in
      blood pressure in White women, these findings have not been replicated among
      African-American women. The purpose of this study was to determine if the number
      of pregnancies urban African-American women have effects BMI and blood pressure
      readings later in life. Results indicated that women with a previous diagnosis of
      hypertension had higher SBP and DBP, and a slightly higher BMI than women who had
      never been diagnosed. Additionally, women with a prior history of hypertension
      had more children than those without a diagnosis of hypertension. As parity
      increased, SBP increased. However, DBP decreased after 3 to 4 children, even with
      increases in BMI. This study shows that parity may increase African-American
      women's risk for hypertension in terms of increased SBP and BMI with increased
      parity. However, increased parity and BMI may also serve as protective factors in
      lowering DBP. Further studies, with larger samples followed throughout their
      pregnancies, is needed before more definitive statements may be drawn about the
      effects of parity on BMI and blood pressure readings among African-American women
      can be made.

PMID- 19397050
TI  - The quality of diabetes care to Gullah families of South Carolina.
AB  - Empirical evidence from the Diabetes Control and Complication Trial (DCCT)
      suggests that maintaining normal glycemic control can prevent both micro vascular
      and macro vascular diseases in persons diagnosed with type 2 diabetes mellitus
      (T2DM) (DCCT, 1993). Adults with T2DM are also more likely to have hypertension
      (73% [HTN]) and patients with both are 2 to 4 times more likely to develop
      diabetic complications compared with the general population (CDC, 2005). The
      purpose of this descriptive study was to 1) describe the quality of diabetes care
      received by Gullah families who participated in the Project SuGar research study;
      and 2) compare the Gullah's quality of care to the national sample in the Center
      for Disease Control (CDC) Diabetes Report Card using the two indicators of blood
      pressure and HbA1c. This was a secondary analysis from a parent study that
      compared selected data to the CDC Diabetes Report Card, the National Health and
      Nutrition Examination Survey (NHANES III), and the Behavioral Risk Factor
      Surveillance System (BRFSS). Socio-demographic and clinical data were obtained
      from 1,057 research participants (N = 1,057). Overall, when compared to the
      national sample in the CDC Report Card, the HbA1c greater than 9.5% mg/dL was
      higher among the Gullahs, (30.2% vs. 18%), and blood pressure greater 140/90 mmHg
      was lower (29% vs. 34%) among the participants. Almost half of the Gullahs
      (45.9%) self-reported neurovascular complications such as foot pain,
      claudication, and renal complications of kidney infection and dialysis (7.3%).
      The Gullah study participants are at risk for diabetes-related complications.
      Results suggest a quality gap in diabetes care and it suggests health disparities
      in outcome measures as well. Optimal care that is consistent with clinical
      guidelines could have a significant impact on decreasing complications and health
      disparities.

PMID- 19397051
TI  - Relationship between obesity's adverse health risk and body mass index in African
      American women.
AB  - Overweight and obesity are major threats to public health in the United States,
      affecting more than 60% of the adult population. African-American women are
      disproportionately represented in the largest increases of overweight and obese
      Americans, and they are at greater risk for poor health and obesity's related
      disorders. This descriptive study assessed African-American women's knowledge of
      obesity's adverse consequences and examined the relationship between their
      knowledge of obesity's health risk and their body mass index (BMI). Data were
      analyzed using Pearson Product Moment Correlation, ANOVA, paired t test, and Chi
      square test. Findings from the study suggested that African-American women in
      this study had a moderate knowledge of obesity's adverse consequences. No
      relationship was observed between African-American women's knowledge of obesity's
      adverse consequences and their BMIs. In addition, findings suggested that there
      is a strong need to develop educational programs addressing obesity's adverse
      consequences, targeting women with a high school or less education.

PMID- 19397052
TI  - African-American college women's perceptions of resources and barriers when
      reporting forced sex.
AB  - Forced sex is both a public health and a social issue that affects many college
      women. Despite physical and mental health consequences and the multiple
      prevention programs on college campuses, most sexual violence goes unreported
      (Fisher, Daigle, Cullen, & Turner, 2003). The purpose of this research was to
      explore college women's perceptions of campus resources and to determine the
      perceived barriers to reporting sexual violence. After IRB approval, African
      American women (N = 144) who attend a private college in the south completed a
      researcher-developed survey. Findings included percentages of reporting sexual
      violence to campus health, student services, and campus security. Significant
      factors that were associated with reporting sexual violence included having
      injuries, if they were drinking at the time, having a designated person on campus
      to handle sexual assault, having time to go to the authorities, and the
      perception of how one would be treated. Reporting of forced sex is necessary so
      that individuals have access to resources and support. Prevention strategies can
      include education that targets significant perceptions of resources and the
      elimination or minimization of barriers.

PMID- 19397053
TI  - Teaching strategies to facilitate breast cancer screening by African-American
      women.
AB  - The objective of this paper is to report on the recent literature concerning
      coverage of breast cancer epidemiology, the barriers to breast cancer screening,
      and the strategies to facilitate screening by African-American women. Based on
      these findings, the author suggests culturally appropriate techniques to be used
      to promote breast cancer screening in African-American women. Barriers to breast
      cancer screening in African-American women include emotional reasons,
      spiritual/religious reasons, fatalism, logistic concerns, lack of knowledge, and
      lack of follow-up by health-care professionals. Numerous strategies that have
      been targeted toward African-American women are reported. These include
      storytelling, witnessing, and testimonies; providing social support and having
      social support networks; and conducting multifaceted programs that include
      culturally specific breast health information. Based on the literature reviewed,
      the author suggests some examples of creative and culturally appropriate
      techniques that have been implemented with African-American women and that have
      resulted in positive feedback. These examples include the use of testimonies,
      photographs, prose, narratives, poetry, and quotations.

PMID- 19397054
TI  - Factors that shape mental health treatment-seeking behaviors of HIV-positive
      African-American women with depressive symptoms: a review of the literature.
AB  - Acquired immune deficiency syndrome (AIDS) remains a leading cause of death for
      African-American women from 25 to 34 years of age. Depressive symptoms are
      commonly associated with the diagnosis of AIDS. Highly active antiretroviral
      therapy (HAART) is needed for optimal treatment; however, African-American women
      who are infected with the human immunodeficiency virus (HIV) and who experience
      depressive symptoms have low and/or inconsistent use of HAART. Additionally,
      behaviors associated with untreated depressive symptoms increase the chances for
      HIV transmission. Clinicians, therefore, need to recognize both the individual
      and the contextual factors that influence those seeking treatment for depressive
      symptoms. The purpose of this article is to gain a better understanding of the
      factors that shape treatment seeking for depressive symptoms among HIV-positive
      African-American women, an important variable in secondary HIV prevention. Multi
      contextual underpinnings shape this phenomenon; therefore, Bronfenbrenner's
      ecological framework was used to organize this literature review. Knowledge
      gained from this paper can support the promotion of health and can prevent or
      manage depressive symptoms among this vulnerable group.

PMID- 19397055
TI  - Sisters Together: Move More, Eat Better: a community-based health awareness
      program for African-American women.
AB  - Statistics indicate that African-American women have the highest rate of obesity
      among all racial groups. In response, the National Institute of Diabetes and
      Digestive and Kidney Diseases (NIDDK) developed "Sisters Together: Move More, Eat
      Better," a national program that encourages African-American women to maintain a
      healthy weight by becoming more physically active and by eating healthier foods.
      "Sisters Together" programs are run locally by individuals or community groups in
      locations such as churches and health departments. The NIDDK offers culturally
      relevant materials and technical assistance to program leaders, including a
      recently updated program guide. The guide walks leaders through program planning,
      promotion, implementation, and evaluation. It is based on obesity, nutrition, and
      physical activity research; evidence-based programs for African-American women;
      and proven health communication strategies. The guide is consumer friendly, using
      clear language and real-life examples. "Sisters Together" programs encourage
      African-American women and their families to improve their eating habits and
      their physical activity habits.

PMID- 19397056
TI  - Leadership and quality top NHS agenda.
AB  - In December 2008 the Department of Health released the new operating framework
      for 2009/10 (DH 2008a). The framework highlights key principles around the
      provision of care for patients in the NHS and prime among these are the emphasis
      placed on leadership and quality. The theme throughout is that patient experience
      is the key indicator of success for the NHS.

PMID- 19397058
TI  - The trouble with older people.

PMID- 19397059
TI  - Health economics: what value to the theatre practitioner?
AB  - Clinical effectiveness has become embedded into healthcare in the last decade. In
      juxtaposition with this philosophy lies health economics with its mantra of
      resources being finite, whilst the need for healthcare remains infinite. An
      outline of a provocative cost-benefit analysis is provided to increase the
      knowledge of health economics for those working in the operating department. This
      paper argues that cost effectiveness must be embedded within clinical
      effectiveness.

PMID- 19397060
TI  - A patient's journey through the operating department from an infection control
      perspective.
AB  - The path a patient negotiates through an operating department is shaped by its
      design and layout, which should be determined by infection control requirements
      to ensure the safety of both patients and practitioners. How this is achieved is
      discussed in relation to an operating department in a local trust, together with
      how infection control, and therefore the prevention of surgical site infection,
      is achieved through hospital policies and key practices within a theatre by
      theatre practitioners and surgeons.

PMID- 19397061
TI  - Surgical management of fractured neck of femur.
AB  - The fractured neck of femur is the classically described fracture in osteoporotic
      elderly patients. Further, the fracture has a strong predominance in post
      menopausal women and, although relatively uncommon in both children and young
      adults, where present in this age group it is usually the result of significant
      trauma. In elderly patients, with an already weakened bone, even minimal trauma
      may be sufficient to cause fracture and as such a fractured neck of femur is
      often referred to as a fragility fracture.

PMID- 19397062
TI  - Reflections on a perioperative career: 1970-2008.
AB  - This paper is a personal journey through nurse training and perioperative
      practice. Nurse education is also explored alongside some of the social, academic
      and political changes that have influenced healthcare in the United Kingdom
      between 1966 and 2008. The views expressed are those of the author only, and the
      anecdotal descriptions are anonymous.

PMID- 19397063
TI  - To catheterise or not to catheterise: study in hip and knee primary arthroplasty.
AB  - This cross sectional study examines the rate of catheterisation of patients after
      elective primary hip and knee arthroplasty in an English district general
      hospital. 50 patients were included in this study, with 19 (37%) being
      catheterised pre-operatively. Of the remainder, 10 went into retention and had to
      be catheterised, while the other 21 were managed without a catheter. There was a
      trend towards more patients requiring catheterisation after axial anaesthetic
      (42%) compared to non-axial anaesthetic (21%), although this was not significant.
      We examine the rationale for catheterisation in hip and knee arthroplasty and
      review the available literature.

PMID- 19397064
TI  - Eleanor Davies-Colley: the first woman F.RC.S.

PMID- 19397065
TI  - The OR: smoking in a designated non-smoking area.

PMID- 19397066
TI  - The challenge for dental schools: keeping up with the evolution of technology.

PMID- 19397067
TI  - Volunteering for the long-term good.

PMID- 19397068
TI  - Revisiting the hopeless ridge: part I--challenging the gold standard.
AB  - Proper bone-augmentation strategies are essential to recreating natural function
      and esthetics, implant dentistry's paramount objective. Although autogenous
      grafts have historically been considered the gold standard among grafting
      materials, they are associated with higher complication rates, greater
      resorption, and lower implant success than some of the allograft alternatives.
      Demineralized allograft bone combined with a carrier that facilitates handling
      has been verified to be inductive and offer other benefits. Three reports are
      presented of patients treated with such allograft materials in combination with
      resorbable membranes.

PMID- 19397069
TI  - Prescribing NSAIDs to patients on SSRIs: possible adverse drug interaction of
      importance to dental practitioners.
AB  - Abstract: The potential for adverse drug interactions is a growing concern for
      dental practitioners. Recent studies report an increased risk of gastrointestinal
      (GI) bleeding when nonsteroidal antiinflammatory drugs (NSAIDs) are taken
      concomitantly with selective serotonin reuptake inhibitors (SSRIs) than when
      either class of drugs is taken alone. A PubMed structured search was performed
      for published English language literature analyzing the epidemiology of this
      interaction between January 1, 1997 and December 31, 2007. Four cohort and five
      case-control studies were included in the final selection. Most studies show an
      increased risk for developing GI bleeding with concurrent use of SSRIs and
      NSAIDs, reporting an odds ratio between 1.8 and 15.6. Seven studies were done on
      adult European Caucasian populations, one in Canada, and one in the United
      States, with follow-up data collected ranging from 6 months to 13 years. The
      primary limitation was the variation in methodology, inclusion criteria,
      comparison groups, and statistical analyses. A significant correlation between
      the combination of these drugs and GI bleeding has been reported in retrospective
      studies. Nonetheless, a causal inference cannot be made based on the available
      evidence and the lack of randomized controlled clinical trials.

PMID- 19397070
TI  - Clinical case report: treatment of anterior teeth with an implant, veneers, and
      full-coverage restorations.

PMID- 19397071
TI  - Computer-generated implant planning and surgery: case select.

PMID- 19397072
TI  - Caring for families: double binds in neuroscience nursing.
AB  - Despite the proliferation of literature related to nurse-family relationships,
      little is known about such relationships in acute care neuroscience environments.
      A grounded theory study illuminated the experiences of nurses caring for families
      of patients with acquired brain injuries in the context of acute care hospital
      environments. Nurses, working in pressure-cooker-like environments, tried to meet
      information and emotional needs of families. During data analysis, a
      communication pattern emerged that impacted on nurses' experiences and
      relationships with families. This communication pattern, known as a double bind,
      contributed to a pattern of nursing that emerged and offers an explanation for
      the behaviours of the nurses in coping with family members. Nurses felt "damned
      if they did and damned if they didn't". To provide family-centred care, we need
      to fully understand the experiences of nurses caring for these families. This
      paper describes the concept of double bind and its application to neuroscience
      nursing.

PMID- 19397074
TI  - The male question.

PMID- 19397073
TI  - The efficacy of 5-HT3 receptor antagonists for the prevention of postoperative
      vomiting following craniotomy: two studies in children and young adults.
AB  - The purpose of this meta-analysis was to estimate the efficacy of prophylactic
      administration of 5-HT3 receptor antagonists for postoperative vomiting (POV) in
      pediatric craniotomy patients at 24 hours. By updating a previously published
      systematic literature search, we found a recently published pediatric study to
      combine with the one already identified. The two published randomized placebo
      controlled trials were combined for a total of 135 participants aged 2 to 20 (79
      treatment and 56 controls). The only study drug was ondansetron. The combined
      relative risk (RR) of vomiting was not statistically significant in the treatment
      group compared to the control group (RR = 0.77; 95% CI: 0.50-1.19). There was
      also no evidence of efficacy for ondansetron in reducing the use of rescue
      antiemetics in the treatment group compared to the control group (RR = .71; 95%
      CI: 0.34-1.49). While combining these randomized placebo-controlled trials did
      not show efficacy for ondansetron in preventing POV in craniotomy patients aged 2
      to 20, a clinically significant effect cannot be excluded, as even the combined
      sample size remained small. Thus, there is no current evidence for or against
      this class of drugs for preventing POV in children after craniotomy, and clinical
      decision-making must be based on studies in other populations and clinical
      experience. Ongoing assessment of nausea and vomiting and ongoing evaluation of
      the effectiveness of treatments in individual children and young adults remains
      an essential part of perianesthesia and postoperative neuroscience nursing.

PMID- 19397075
TI  - Health visiting promise to protect children.

PMID- 19397076
TI  - Boys: half the solution.

PMID- 19397077
TI  - Missing men.

PMID- 19397078
TI  - Getting out there.

PMID- 19397079
TI  - Including fathers in preventing non-accidental head injury.
AB  - Health visitors identified fathers as a marginalised, difficult-to-reach group
      when aiming for universal implementation of a public health programme to prevent
      non-accidental head injury (NAHI) in babies. Follow-on research with 30 fathers
      from disadvantaged backgrounds, including some in prison, explored barriers and
      facilitating factors to preventing NAHI through focus groups and interviews.
      Fathers expressed both responsibility and helplessness in managing a baby, but
      many felt excluded from gaining skills and knowledge by healthcare staff.
      Barriers to implementing a prevention programme included a lack of knowledge
      about head injuries in babies and poor understanding of prevention as a reduction
      of risk factors. Fear of blame for a head injury could lead to injury
      concealment, indicating a taboo subject. Facilitators for fathers to learn about
      preventing head injuries in babies included concerns of their masculinity being
      at odds with the frailty of the newborn, recognition of fathers' needs to be
      valued in their own right, and a need for individualised plans for gaining
      information and increasing confidence. The modifiable barriers to prevention,
      from the fathers' perspectives, add to the theoretical and applied evidence base
      for the prevention of NAHI.

PMID- 19397080
TI  - 'He'll not talk to anyone': researching men on low incomes.
AB  - This paper explores the difficulties of undertaking research with men living on
      low incomes. The literature shows that most social research undertaken with men
      has been based on groups of men from higher socioeconomic groups--predominantly
      from those in work, where access is less problematic than with those who are
      unemployed.A research project is used as an example to demonstrate the
      difficulties of accessing men from low socio-economic groups. It is more
      difficult to make contact with men in the privacy of the home, which is often
      perceived as the woman's domain. Women may consequently act as gatekeepers to
      men. A community development approach can overcome these difficulties, because
      the researcher is known within the community. Despite this, a female researcher
      working within the private domain of the home can still face problems in engaging
      men in discussion.

PMID- 19397081
TI  - Fathers and parenting programmes: barriers and best practice.
AB  - Fathers are particularly difficult to recruit to voluntary parenting programmes,
      despite the advantages of such programmes for confidence and skills in parenting
      and associated improvements in child behaviour. The apparent reluctance of
      fathers to engage in parenting services is recognised as a problem by health and
      social care practitioners, and the Department of Health identifies the engagement
      of fathers as a key service target. This review gathers information on barriers
      to fathers' engagement with parenting support services and identifies best
      practice for recruitment. It draws on published academic literature, government
      and community organisation reports and empirical data collection through
      interviews with parenting experts (n=9) and focus groups and questionnaires with
      fathers (n=29). The barriers identified were lack of awareness, work commitments,
      female-orientated services, lack of organisational support and concerns over
      programme content. Aspects of best practice included actively promoting services
      to fathers rather than parents, offering alternative forms of provision,
      prioritising fathers within organisations and taking different cultural and
      ethnic perspectives into account. Achieving greater engagement of fathers in
      parenting support programmes requires a greater understanding of the perspectives
      of fathers.

PMID- 19397082
TI  - Older men: batting on.

PMID- 19397083
TI  - Men: showing willing.

PMID- 19397084
TI  - Bullying and disclosure.

PMID- 19397085
TI  - Is the National Child Measurement Programme a waste of money?

PMID- 19397086
TI  - 'These strangers within our gates': race, psychiatry and mental illness among
      black Americans at St Elizabeths Hospital in Washington, DC, 1900-40.
AB  - During the early decades of the twentieth century, William Alanson White and the
      medical staff at St Elizabeths Hospital in Washington, DC, developed an ambitious
      programme for US psychiatry wherein the profession would dedicate itself to the
      reconstitution of mentally-fit and socially-productive American citizens. The
      racist assumptions beneath this programme led most physicians at the institution
      to expect little more than deference, dependence and common labour from their
      black patients, preventing them from comprehending the impact of substandard and
      racially-segregated care. Black men and women were acutely aware of the
      injustices they faced. When they rejected elements of the hospital's medical
      regimen, these patients were also rejecting a social vision that consigned them
      to the margins of US civic life.

PMID- 19397087
TI  - Asylum and community: the Athens Lunatic Asylum in nineteenth-century Ohio.
AB  - This paper examines the role of the village of Athens, Ohio, USA, in the founding
      and operation of the Athens Lunatic Asylum during the nineteenth century. Taking
      as its sources official, personal and popular culture documents, the paper
      focuses on the function of this Asylum as a participant in the economy of its
      surrounding community. The Athens Lunatic Asylum was deeply connected with its
      community, functioning as a market for local goods and services as well as an
      employer. Connections between the Asylum and the community were supported by a
      physical infrastructure of transportation and utilities as well as a political
      infrastructure that operated locally and at the state level. Implications for
      mental health care and for community are proposed.

PMID- 19397088
TI  - The introduction of the concept of dementia praecox into Spain, 1902-19.
AB  - Modern psychiatry has been shaped by Emil Kraepelin's nosological revolution.
      Historiography, accordingly, has taken an interest in how his ideas on psychiatry
      were introduced in different countries. This article will analyse the
      introduction of dementia praecox into Spanish psychiatry and its relationship
      with the theoretical debate taking place there at the time in the context of
      Spanish psychiatric care and institutions.

PMID- 19397089
TI  - Managing the 'unmanageable': interwar child psychiatry at the Maudsley Hospital,
      London.
AB  - When opened as a post-graduate teaching and research hospital in 1923, the
      Maudsley made virtually no provision for the treatment of children. Yet its
      children's department saw sustained growth during the interwar period. This
      expansion is explored in relation to novel behaviourist hypotheses and the
      forging of formal links with local government and charitable bodies. The
      recruitment of psychologists, educators and specialist social workers fostered a
      multidisciplinary approach through case conferences. This development would
      structure the theoretical origins of child psychiatry, in particular influencing
      the role and interpretation of psychoanalytic theory within it. The theoretical
      orientation of child psychiatry and the practical treatment of children
      represented an area of dynamic change and innovation at a time when adult
      psychiatry struggled to discover effective treatments or achieve breakthroughs in
      causal understanding.

PMID- 19397090
TI  - Psychosurgery in Italy, 1936-39.
AB  - In 1936 Egas Moniz introduced a new method for treating mental illness-
      psychosurgery. This new procedure was taken up immediately in a number of
      countries, including Italy. In most countries its introduction was slow and the
      numbers of operations were in single figures, but in Italy the introduction was
      rapid and around a dozen neuropsychiatrists reported much higher numbers of
      operations performed. Also in Italy the first innovations to the technique,
      notably the transorbital variation, were introduced. Moreover, all these
      activities took place without any sign of the protest seen elsewhere. Conditions
      that allowed the acceptance of this risky procedure seemed to be a consequence of
      the way in which the professions of neurology and psychiatry had been merged in
      Italy.

PMID- 19397091
TI  - Coming together as partners to address the nursing shortage.

PMID- 19397092
TI  - Implementing a pharmacy system: facilitators and barriers.
AB  - To describe facilitators and barriers to the implementation of an inpatient
      pharmacy system at two pediatric hospitals. Interviews, pre- and post
      implementation, were conducted with pharmacy and clinical managers. Key findings
      from the pre-implementation survey were included in the post-implementation
      survey to further assess facilitators and barriers to the adoption of a pharmacy
      system. The majority of pharmacy participants and all clinical leaders believed
      that project goals were being met. Pharmacist's described staff readiness-to
      change as the most significant facilitator to adoption and concerns with the
      usability of information in the pediatric drug file as the most significant
      barrier. Clinical managers described system training and education as the most
      significant facilitator to adoption and adjustment to new work processes as the
      most significant barrier. We described major facilitators and barriers to the
      adoption of an inpatient pharmacy system at two pediatric hospitals. Strategies
      identified by our informants to overcome barriers may promote successful pharmacy
      implementations at other pediatric facilities.

PMID- 19397093
TI  - Artificial neural network to predict skeletal metastasis in patients with
      prostate cancer.
AB  - The application of an artificial neural network (ANN) in prediction of outcomes
      using clinical data is being increasingly used. The aim of this study was to
      assess whether an ANN model is a useful tool for predicting skeletal metastasis
      in patients with prostate cancer. Consecutive patients with prostate cancer who
      underwent the technetium-99m methylene diphosphate (Tc-99m MDP) whole body bone
      scintigraphies were retrospectively analyzed between 2001 and 2005. The
      predictors were the patient's age and radioimmunometric serum PSA concentration.
      The outcome variable was dichotomous, either skeletal metastasis or non-skeletal
      metastasis, based on the results of Tc-99m MDP whole body bone scintigraphy. To
      assess the performance for classification model in clinical study, the
      discrimination and calibration of an ANN model was calculated. The enrolled
      subjects consisted of 111 consecutive male patients aged 72.41 +/- 7.69 years
      with prostate cancer. Sixty-seven patients (60.4%) had skeletal metastasis based
      on the scintigraphic diagnosis. The final best architecture of neural network
      model was four-layered perceptrons. The area under the receiver-operating
      characteristics curve (0.88 +/- 0.07) revealed excellent discriminatory power (p
      < 0.001) with the best simultaneous sensitivity (87.5%) and specificity (83.3%).
      The Hosmer-Lemeshow statistic was 6.74 (p = 0.08 > 0.05), which represented a
      good-fit calibration. These results suggest that an ANN, which is based on
      limited clinical parameters, appears to be a promising method in forecasting of
      the skeletal metastasis in patients with prostate cancer.

PMID- 19397094
TI  - Investigation of the arterial stiffness on renal artery Doppler sonograms.
AB  - This study aims to identify the effect of stiffness on renal artery Doppler
      sonograms by using a curve fitting approach. The study includes 20 patients with
      suspected renovascular hypertension. Each patient underwent recordings during
      renal artery examinations before and after administration of Captopril 25 mg
      (Kapril tablet, MN Pharmaceuticals, Istanbul, Turkey). Doppler signals were
      analyzed with short time Fourier transformation, followed by curve fitting to
      sonograms using Savitzky-Golay method. Doppler parameters obtained from pre- and
      post-Captopril curve-fitted sonograms were statistically compared with "Paired
      Samples t-Test". Captopril administration resulted in a significant decrease in
      the mean frequency and a significant increase in Pulsatility Index of the
      periods. No significant difference was detected between maximum systolic and
      minimum diastolic frequencies, Resistivity Index, and the Acceleration Index. The
      computational approach in this study appears to be promising.

PMID- 19397095
TI  - Neural network-based computer-aided diagnosis in classification of primary
      generalized epilepsy by EEG signals.
AB  - Epilepsy is a disorder of cortical excitability and still an important medical
      problem. The correct diagnosis of a patient's epilepsy syndrome clarifies the
      choice of drug treatment and also allows an accurate assessment of prognosis in
      many cases. The aim of this study is to classify subgroups of primary generalized
      epilepsy by using Multilayer Perceptron Neural Networks (MLPNNs). This is the
      first study classifying primary generalized epilepsy using MLPNNs. MLPNN
      classified primary generalized epilepsy with the accuracy of 84.4%. This model
      also classified generalized tonik-klonik, absans, myoclonic and more than one
      type seizures epilepsy groups correctly with the accuracy of 78.5%, 80%, 50% and
      91.6%, respectively. Moreover, new MLPNNs were constructed for determining
      significant variables affecting the classification accuracy of neural networks.
      The loss of consciousness in the course of seizure time variable caused the
      largest decrease in the classification accuracy when it was left out. These
      outcomes indicate that this model classified the subgroups of primary generalized
      epilepsy successfully.

PMID- 19397096
TI  - Medical informatics: a model developed for diabetes education via telemedicine.
AB  - Fast developments in information and communication technology (ICT) have made it
      possible to develop new services for people. One of the most interesting areas is
      health care. Medical informatics is the discipline concerned with the systematic
      processing of data, information and knowledge in medicine and health care.
      Information services, medical decision support systems and telemedicine are
      becoming important tools for medical professionals and also people who are
      interested in health related information. Medical decision support aims at
      providing health care professionals with therapy guidelines directly at the point
      of care. Telemedicine is the use of modern telecommunications and information
      technologies (IT) for the provision of clinical care to individuals at a distance
      and transmission of information to provide that care. In the present study, usage
      of IT in medicine, medical decision support systems, computerized medical
      measurements, patient education and network connectivity were described. A model
      for risk evaluation, data collection and education of undiagnosed diabetes using
      the world wide web (www) was presented.

PMID- 19397097
TI  - A new feature detection mechanism and its application in secured ECG transmission
      with noise masking.
AB  - With cardiovascular disease as the number one killer of modern era,
      Electrocardiogram (ECG) is collected, stored and transmitted in greater frequency
      than ever before. However, in reality, ECG is rarely transmitted and stored in a
      secured manner. Recent research shows that eavesdropper can reveal the identity
      and cardiovascular condition from an intercepted ECG. Therefore, ECG data must be
      anonymized before transmission over the network and also stored as such in
      medical repositories. To achieve this, first of all, this paper presents a new
      ECG feature detection mechanism, which was compared against existing cross
      correlation (CC) based template matching algorithms. Two types of CC methods were
      used for comparison. Compared to the CC based approaches, which had 40% and 53%
      misclassification rates, the proposed detection algorithm did not perform any
      single misclassification. Secondly, a new ECG obfuscation method was designed and
      implemented on 15 subjects using added noises corresponding to each of the ECG
      features. This obfuscated ECG can be freely distributed over the internet without
      the necessity of encryption, since the original features needed to identify
      personal information of the patient remain concealed. Only authorized personnel
      possessing a secret key will be able to reconstruct the original ECG from the
      obfuscated ECG. Distribution of the would appear as regular ECG without
      encryption. Therefore, traditional decryption techniques including powerful brute
      force attack are useless against this obfuscation.

PMID- 19397098
TI  - Factors influencing computer literacy of Taiwan and South Korea nurses.
AB  - Healthcare is experiencing a major transformation in its information technology
      base. Hospitals are adopting information technology (IT) to reduce costs and
      increase competitiveness. IT applications in healthcare are trending towards
      electronic patient records and even health records. Therefore, practices in
      nursing are also affected by IT. Many researchers have studied what computer
      literacy a nurse should possess, but have focused less on factors that actually
      impact computer literacy. The purposes of this study are to examine current
      computer literacy levels of nurses, and to indicate what variables influence
      their computer literacy. Taiwan and South Korea both implemented a national
      health insurance system, and used state-of-the art IT to provide higher volume
      and better quality of services. The data were collected from two case hospitals
      which are located in Taiwan and South Korea, respectively. By using a structured
      questionnaire, a total of 203 nurses responded; 104 from Taiwan and 99 from South
      Korea. The results revealed that personal innovativeness in IT, computer
      education, and age are significant factors that affected computer literacy
      levels. These factors serve as reference for administrators and executives in
      hospitals, or nursing educators seeking the data necessary to make decisions on
      curriculum.

PMID- 19397099
TI  - Comparative study on the use of analytical software to identify the different
      stages of breast cancer using discrete temperature data.
AB  - Breast cancer is the second leading cause of death in women. It occurs when cells
      in the breast begin to grow out of control and invade nearby tissues or spread
      throughout the body. The limitations of mammography as a screening modality,
      especially in young women with denser breasts, necessitated the development of
      novel and more effective screening strategies with acceptable sensitivity and
      specificity. The aim of this study was to develop a feasible interpretive
      software system which was able to detect and classify breast cancer patients by
      employing techniques of different analytical software. The protocol described
      uses 6,000 pieces of thermal data collected from 16-sensors, eight placed on the
      surface of each breast. Data was collected every 5 min for the duration of the
      test period. Placement of sensors was accomplished with the use of a template
      design from information provided by the national tumor registry to insure that
      the information was collected in areas of the breast where most breast cancers
      develop. Data in this study was collected from 90 individuals exhibiting four
      different breast conditions, namely: normal, benign, cancer and suspected-cancer.
      The temperature data collected from these 16 sensors placed on the surface of
      each breast were fed as inputs to the classifiers. Comparisons were made on five
      different kinds of classifiers: back-propagation algorithm, probabilistic neural
      network, fuzzy (Sugeno-type), Gaussian mixture modeland support vector machine.
      These classifiers were able to attain approximately 80% accuracy in classifying
      the four different diagnoses (normal, benign, cancer and suspected-cancer).
      Gaussian mixture model was the most sensitive classifier, achieving the highest
      sensitivity of 94.8%. Support vector machine was considered the best classifier
      as it was able to produce the most specific and accurate results. Based on these
      evaluations, this current effort shows the feasibility of applying analytical
      software techniques together with the real-time functional thermal analysis to
      develop a potential tool for the detection and classification of breast cancer.

PMID- 19397100
TI  - Improving doctor-patient communication: examining innovative modalities vis-a-vis
      effective patient-centric care management technology.
AB  - This analysis investigates what patients and practitioners can do to improve
      their interactive communications to achieve optimal patient-centric (PC) care.
      One goal of this clinical practice approach is to improve patient satisfaction,
      compliance, and outcomes. The mutual responsibilities required of both the
      patients and practitioners to attain PC care are discussed. Innovative,
      information technology techniques in the healthcare environment in general and in
      care delivery in particular are explored. Practitioner-to-patient encouragement
      vis-a-vis self education on their conditions is also provided.

PMID- 19397101
TI  - The hijacking of American medicine by the Federal Trade Commission & the
      Department of Justice.

PMID- 19397102
TI  - The forecast: blue skies for the Missouri JUA with winds from the west carrying
      the Stabilization Fund.

PMID- 19397103
TI  - Dramatic changes to Stark Law: is your organization ready to respond?

PMID- 19397104
TI  - Responding to Missouri's health professions shortages: the right thing to do, the
      smart thing to do.

PMID- 19397105
TI  - The Missouri Unviersity School of Health Professions: high tech, high touch care.

PMID- 19397106
TI  - Who will provide future health care? Missouri's health workforce crisis.

PMID- 19397107
TI  - January 2009, Taliban and the end of trick or treating.

PMID- 19397108
TI  - Considering retirement? Some things to think about.

PMID- 19397110
TI  - What has the MSMA done for me lately?

PMID- 19397109
TI  - DVT article correct.

PMID- 19397111
TI  - Too many weak days--diagnosis: physical frailty.
AB  - Physical frailty is increasing among older adults; half of all those over 85
      years are unable to independently accomplish activities of daily living. Gait
      speed is often compromised which results in diminished functional community
      independence. This article defines frailty and identifies the risk factors for
      frailty, as most are modifiable with diet and exercise interventions. Frailty is
      treatable but ideally, frailty should be prevented as it cannot be cured.

PMID- 19397112
TI  - Breast cancer and "chemobrain": the consequences of cognitive difficulties
      following chemotherapy and the potential for recovery.
AB  - Up to one-third of women breast cancer survivors report difficulties with
      concentration, multi-tasking, and memory. Research in the University of Missouri,
      Department of Health Psychology, suggests that these cognitive difficulties are
      associated with poorer quality of life among breast cancer survivors after
      treatment. This article discusses this treatment side effect and its consequences
      for daily functioning, highlights ongoing research on the potential role of
      stress in the development of cognitive difficulties, and reviews treatment
      options.

PMID- 19397113
TI  - Accuracy of a non-radiographic method of measuring varus/valgus alignment in
      knees with osteoarthritis.
AB  - Knee alignment has been shown to affect incidence, progression and treatment of
      knee osteoarthritis (OA). The gold standard for measuring alignment is a
      radiograph that is often difficult to obtain. This study demonstrates that a
      clinical non-radiographic measure can serve as a surrogate assessment of knee
      alignment in older adults with knee OA. We believe these findings will allow more
      widespread evaluation of one critical mechanical factor essential to the study of
      knee OA.

PMID- 19397114
TI  - The development of language and literacy: evaluating the stereotypes.
AB  - People hold many stereotypes about the development of language and reading. We
      review current data concerning three stereotypes: (1) Girls learn language faster
      than boys; (2) Biological factors determine the time course of language
      acquisition; and (3) Dyslexia is a visual problem involving the reversal of
      letters. In each case, recent data leads to a different picture of the
      acquisition of language and literacy and deepens our understanding of the
      processes involved.

PMID- 19397115
TI  - Spirituality, religion and health outcomes research: findings from the Center on
      Religion and the Professions.
AB  - The Spirituality and Health Research Project of the MU Center on Religion and the
      Professions is investigating the relationships that exist among religion,
      spirituality, and health for persons with heterogeneous medical conditions. Pilot
      studies indicate that spirituality and congregational support are related to
      health outcomes, but religious practices are not. Additional research indicates
      that spiritual experiences are related to diminished right parietal functioning
      (through meditation/ prayer or brain injury), which is associated with decreased
      sense of the self. Implications for health professionals are discussed.

PMID- 19397116
TI  - Occupational therapy: evidence-based interventions for stroke.
AB  - Persons with stroke are commonly provided rehabilitation by occupational
      therapists. Occupational therapy endeavors to restore the person's independence
      in activities of daily living, skills in functional performance, infuse evidence
      based practice to assure that interventions are efficacious and cost effective.
      This article reviews the literature and describes a variety of evidence-based
      interventions. This review will provide physicians and other health care
      provider's insights about the best practices in occupational therapy.

PMID- 19397117
TI  - Stroke: a focus on rehabilitative medicine.
AB  - Stroke is the most common neurological cause of long-term disability. While many
      patients show spontaneous functional improvement in the period immediately after
      a stroke, a multidisciplinary program of rehabilitative therapy is essential if
      the patient is to minimize their deficits and maximize their functional
      independence and quality of life. Southeast Missouri Hospital, a community
      hospital located in a rural part of the state, provides a full range of
      coordinated stroke rehabilitation therapies, both inpatient and outpatient. We
      report here the case of a 60-year-old stroke patient who achieved remarkable
      improvements in his abilities and independence through our program.

PMID- 19397119
TI  - Press bias damages relationships.

PMID- 19397118
TI  - Nontraumatic headaches in the Emergency Department: a systematic approach to
      diagnosis and controversies in two "big ticket" entities.
AB  - Headache is a very common presenting complaint in the Emergency Department (ED).
      While the vast majority of these have benign or self-limited etiologies, there
      are several life or organ threatening causes that must be excluded. This paper
      describes a systematic approach to the history and physical examination in these
      patients. Evidence-based recommendations for which patients should receive
      imaging in the ED are reviewed. Current diagnostic approaches and controversies
      in meningitis and subarachnoid hemorrhage are discussed.

PMID- 19397120
TI  - Recognising the ward sister.

PMID- 19397121
TI  - Nursing views from the front line.
AB  - A self-completion reader survey was sent with the December 2008 issues of RCN
      Publishing's eight specialist monthly journals. Subscribers were asked a series
      of multiple-choice and open-ended questions about their jobs, career paths and
      opinions on the state of nursing in the UK and their specialty. Responses were
      analysed by an independent research company. A total of 1,962 completed
      questionnaires were returned, representing a response rate of 3 per cent.
      Paediatric Nursing was the most widely subscribed to of the eight titles. This
      article examines the responses of Paediatric Nursing readers (n=526) and compares
      them with the overall survey results.

PMID- 19397122
TI  - Distraction techniques for venepuncture: a review.
AB  - Venepuncture is one of the most feared hospital procedures for children and
      inadequate pain management has the potential to affect future care. Distraction
      has been shown to help to reduce procedural distress in children. A thematic
      analysis of relevant literature on distraction techniques revealed that passive
      distraction is more effective than active distraction during venepuncture and
      that the effectiveness of a particular technique depends on the attention
      capacity of the child and their engagement in the distraction activity.

PMID- 19397123
TI  - Preparing staff to provide bereavement support.
AB  - An in-service training programme was developed to meet the needs of an NHS
      palliative care service for children and young people, specifically focused on
      bereavement work. A training day was held every six months that allowed staff to
      share and support each other's practice and to consider how best practice could
      be promoted. Each training day was evaluated by attendees, who were asked to rate
      the usefulness of the day and give qualitative feedback. After four training days
      had been completed, staff views on the impact and benefits of the programme were
      sought using a questionnaire that incorporated a set of statements highlighting
      factors important to good bereavement care. Participant evaluations indicated
      that the aims of the training days were being met. Responses to the questionnaire
      were positive, both in terms of improvement and positive outcomes in the
      workplace. Ongoing training and support as well as clinical supervision are
      essential to maintain good practice in palliative and bereavement care.

PMID- 19397124
TI  - Practice guidelines: information sharing.

PMID- 19397125
TI  - Neurovascular impairment and compartment syndrome.
AB  - Compartment syndrome is a potential complication of musculoskeletal trauma and
      surgery. Early identification of compartment syndrome is critical because, if
      left untreated, it may result in limb loss or death. Nurses routinely perform
      neurovascular observations as a part of the patient's essential care in hospital.
      However, there is limited literature on the assessment and early identification
      of compartment syndrome in children, although most authors agree on assessment
      criteria such as pain, warmth, colour, movement, sensation and pulses. Improved
      approaches to assessment and early recognition may be required so that effective
      action can be taken to reduce the severity of the outcome.

PMID- 19397126
TI  - Transition from nursing student to staff nurse: a personal reflection.
AB  - Mentors, buddies, qualified nurses and other healthcare professionals shape the
      practice experiences of nursing students and change their perceptions on how care
      is delivered in the healthcare environment. Based on these experiences and
      perceptions, the student will decide whether to continue with a career in
      nursing. Once qualified, nurses cannot be expected to know everything. Clinical
      teams must be supportive of staff learning needs, acknowledging that
      relationships with mentors, supervisors and other staff will affect an
      individual's ability to fit in, to ask questions and to feel safe.

PMID- 19397127
TI  - Simulation: issues and challenges.

PMID- 19397128
TI  - Waiting for surgery after orthopaedic trauma.
AB  - Nursing staff on a paediatric surgical ward were concerned about delays
      experienced by children waiting to go to theatre following orthopaedic trauma,
      and their families. A facilitated action research approach was used which
      involved describing the issue, gathering information from a range of sources and
      introducing changes to the process of care. A flowchart was developed to clarify
      the stages and the staff involved in admitting a child with orthopaedic trauma
      for surgery. A white board was introduced to record information on 'trauma'
      patients. A facilitated action research process offers a flexible and accessible
      way for staff to develop a range of transferable research and change management
      skills.

PMID- 19397129
TI  - Use of wound dressings with soft silicone adhesive technology.
AB  - AIM: To evaluate how pain, during and in-between dressing changes, is affected by
      the introduction of Mepilex Border Lite, a wound dressing manufactured by
      Molnlycke Health Care using Safetac soft silicone adhesive technology, to the
      treatment of different types of paediatric wounds/skin injuries. METHODS:
      Wounds/skin injuries that met the criteria for inclusion in the study were
      dressed with Mepilex Border Lite. Patients were followed for six weeks or until
      their wounds/skin injuries had healed, whichever occurred earlier. At each
      dressing change, pain severity before and during dressing removal was rated by
      the patient and the investigator on a scale from zero (no pain at all) to ten
      (worst pain ever). Other variables measured included: signs of trauma to
      wound/skin injury and surrounding skin, the proportion of viable/non-viable
      tissue, the quantity and appearance of exudate, odour, and clinical signs of
      infection. At the final dressing change, patients and investigators completed
      questionnaires to rate the dressing performance. RESULTS: Mean pain severity
      scores were significantly lower (p < or = 0.003) at the first dressing change
      than at baseline. Over 99.5 per cent of the Mepilex Border Lite dressing changes
      were reported to be atraumatic and more than half of the wounds healed within the
      study period. Conformability, ease of use, ease of removal, patient comfort, and
      overall experience with the dressing were rated as 'good' to 'very good' at the
      vast majority of final visit evaluations. CONCLUSIONS: This study provides
      further evidence of the ability of dressings with Safetac soft silicone adhesive
      technology to minimise trauma and pain and demonstrates the ability of Mepilex
      Border Lite to overcome the clinical challenges associated with the use of
      dressings on the wounds/skin injuries of paediatric patients.

PMID- 19397130
TI  - Educating lawmakers: a lobbyist's job.

PMID- 19397131
TI  - The cultural evolution. Part two: culture change or perish: the business case.

PMID- 19397132
TI  - Working on CNA empowerment.

PMID- 19397133
TI  - Hand washing key to preventing spread of infection.

PMID- 19397134
TI  - EMRs aid advance directive documentation.

PMID- 19397135
TI  - Catering to today's seniors.

PMID- 19397136
TI  - Turning customers into crusaders. Leveraging word of mouth through a systematic
      process can improve target marketing and customer satisfaction.

PMID- 19397138
TI  - Lending in a turbulent market. Lenders return to more traditional underwriting
      standards as the industry heads into another period of uncertainty.

PMID- 19397137
TI  - Safe smoking: fact or myth? A detailed and thorough safe smoking policy can
      reduce the risk of fire with effective assessment, communication, and oversight.

PMID- 19397139
TI  - Midwifery knowledge spread around the world.

PMID- 19397140
TI  - Women need all options in cesarean.

PMID- 19397141
TI  - Marion's message. Does it matter how we are born?

PMID- 19397142
TI  - The life and work of a rope midwife in Darfur.

PMID- 19397143
TI  - Emotional impact of cesareans.

PMID- 19397145
TI  - The midwife bond.

PMID- 19397144
TI  - Enoch's home waterbirth after four C-sections.

PMID- 19397146
TI  - Homebirth in Holland.

PMID- 19397147
TI  - Meeting by chance with a modern day Che (a fireside chat with a Cuban
      obstetrician, 2007).

PMID- 19397148
TI  - The influence of birth experience on postpartum depression.

PMID- 19397149
TI  - The power of three and the Bumi Sehat vision.

PMID- 19397150
TI  - The good guys: Michael C. Klein.

PMID- 19397151
TI  - A day in the life of an intern.

PMID- 19397152
TI  - Keeping the midwifery legacy alive.

PMID- 19397153
TI  - Selah's beginnings.

PMID- 19397154
TI  - The midwife.

PMID- 19397155
TI  - Husband-assisted homebirth.

PMID- 19397156
TI  - Birthing in South Africa.

PMID- 19397157
TI  - Why music matters in childbirth.

PMID- 19397158
TI  - Brona.

PMID- 19397159
TI  - Tradition, birth & the kitchen to cook it all in.

PMID- 19397160
TI  - Informed consent.

PMID- 19397161
TI  - Born in Poland.

PMID- 19397162
TI  - The gift.

PMID- 19397163
TI  - The nuchal cord at birth: what do midwives think and do?
AB  - BACKGROUND: No good evidence exists to support the practice of routinely checking
      for the nuchal cord, yet it is a common medical intervention in birth. Some
      evidence shows damage to the baby because the practice more frequently leads to
      premature cord-cutting and the vaginal examination, required by such routine
      checking, may be physically and/or emotionally damaging to the women. Our
      objective was to learn what training midwives have received and what their
      current practice is in relation to a possible nuchal cord at birth? METHOD:
      Questions about nuchal cord at birth were posted to two online midwifery
      discussion forums and responses were invited. Twenty-six midwives from 10
      countries responded to questions on nuchal cord practices. RESULTS: The teaching
      and practice of routinely checking for the nuchal cord at birth is widespread,
      according to at least some participants from all 10 countries. Other midwives
      from the same countries argued that, although they were aware that the procedure
      is the dominant midwifery practice, many midwives neither teach it nor perform it
      routinely. CONCLUSION: In the absence ofclear evidence, firmly entrenched
      positions are being argued for and against routine checking. The debate is
      infused with high emotion. Those arguing for routine checking cite safety for the
      baby as their main concern. Those arguing against checking cite the need to keep
      birth normal and the well-being of the baby as their primary concerns. There is a
      need to reconsider how the possibility of nuchal cord at birth should be
      conceptualised from a midwifery perspective to ensure woman-centred decision
      making.

PMID- 19397164
TI  - Health care with no legs to stand on: the questions behind the question.

PMID- 19397165
TI  - Birth lessons from a chicken.

PMID- 19397166
TI  - Similarities more striking than differences.

PMID- 19397167
TI  - Traditional mentoring.

PMID- 19397168
TI  - Traditional midwives & maternal morbidity & mortalilty in countries with low
      resources.

PMID- 19397169
TI  - Andean traditional midwifery in Peru.

PMID- 19397170
TI  - Nephrology nursing: past and future.

PMID- 19397171
TI  - The value of nursing.

PMID- 19397172
TI  - Forty years of vascular access.
AB  - March 9, 1960, was a milestone marker in end stage renal disease history - the
      date when a patient received the very first arteriovenous Scribner shunt. This
      began the era of maintenance or chronic hemodialysis. With long-term dialysis a
      reality, various new types of vascular access were developed. As the American
      Nephrology Nurses' Association celebrates its 40th anniversary, this article
      looks back to see just how far vascular access has come and what might be in
      store for the future.

PMID- 19397173
TI  - The development of kidney transplant nursing.
AB  - An analysis of published literature, interviews with early transplant nurses, and
      other primary source materials shows how evolving medical treatments for
      rejection, nurses' ability to learn on the job, and their commitment to patients
      influenced the development of kidney transplantation as a specialized area of
      practice. The work of these nurses work is discussed in the context of unfolding
      nursing specialization at the middle of the twentieth century.

PMID- 19397175
TI  - The growth and development of nephrology nursing.

PMID- 19397174
TI  - Nephrology nursing 1915-1970: a historical study of the integration of technology
      and care.
AB  - Findings of this study of the role and functions of nurses working with renal
      dialysis and transplant teams between 1915 and 1970 suggest that many of the
      activities of dialysis and transplant nurses were assistive and technical in
      nature. However, further analysis of the characteristics of direct nursing care
      demonstrates that early nephrology nurses incorporated family support,
      interpersonal communication, and patient teaching as essential components in
      order to assist patients and their families in coping with the stresses of
      receiving these new experimental treatments.

PMID- 19397176
TI  - Peritoneal dialysis nursing--we've come a long way. 2004.

PMID- 19397177
TI  - Industry's contribution to the development of renal care.
AB  - In the early days of dialysis, the practitioner was required to use whatever
      componentry that was available in order to construct dialysis equipment. Sausage
      casing, industrial pumps, and other nonmedical components were used to construct
      the crude dialysis devices. As time passed, industry began to take an interest in
      this unique medical treatment and developed systems that were especially designed
      for dialysis. The collaboration of medicine and industry was critical in the
      development of dialysis as we know it today.

PMID- 19397178
TI  - Reducing early mortality in patients on dialysis: lessons from the RightStart
      program.
AB  - RightStart, a specially designed program for patients new to dialysis,
      incorporates case manager-driven patient education, encouragement, and
      empowerment in conjunction with facilitation of prompt and appropriate care
      provided by the interdisciplinary team. Compared with patients who were not in
      RightStart, participants exhibited a 41% decrease in the risk of death within the
      first 90 days of dialysis (hazard ratio 0.59, P < 0.001). The results suggest
      that a program targeted to new patients on dialysis can significantly reduce
      early mortality and morbidity while increasing job satisfaction for professionals
      in the case manager role.

PMID- 19397179
TI  - A brief history in nephrology pharmacotherapy.
AB  - Advances in drug therapy for patients with kidney disease have contributed to
      increased exercise capacity, reduced cardiovascular disease, decreased renal bone
      disease, improved quality of life, and most importantly, reduced morbidity and
      mortality. New insights into the pathophysiology of chronic kidney disease (CKD)
      have helped lead to the development of many novel drugs and treatments. The
      purpose of this article is to highlight some of the developments in nephrology
      pharmacotherapy that occurred during the first 40 years of the American
      Nephrology Nurses' Association.

PMID- 19397180
TI  - Anemia treatment through the years.

PMID- 19397181
TI  - Levels of change in adolescent sexual behavior in three Asian cities.
AB  - Considerable change in the romantic and sexual behaviors of Asian young people
      may be occurring as traditionally Confucian societies modernize and increase
      outside contacts. This study explores the dimensions and context of this change
      in three sites at different stages in the process of modernization: Hanoi
      (early), Shanghai (intermediate), and Taipei (later stage). A survey was
      conducted of 17,016 males and females aged 15-24 in urban and rural settings in
      three large metropolitan areas. Survival analysis and Cox regressions were
      performed to explore ages of respondents at key transitions and the significance
      of differences between two age cohorts: 15-19 and 20-24. Significant differences
      are found in levels of sexual and other transitions, even within the narrow time
      span reflected by the age cohorts. The findings highlight the differential impact
      of modernization on adolescent sexual behavior as traditional societies undergo
      social change, and they underline the importance of context in exploring youthful
      transitions.

PMID- 19397182
TI  - The persistence of induced abortion in Cuba: exploring the notion of an "abortion
      culture".
AB  - Cuba's annual induced abortion rate persistently ranks among the highest in the
      world, and abortion plays a prominent role in Cuban fertility regulation despite
      widespread contraceptive prevalence and state promotion of modern contraceptives.
      We explore this phenomenon using the concept of an "abortion culture," typically
      used in reference to Soviet and post-Soviet countries. We synthesize existing
      literature to provide a historical account of abortion and contraception in Cuba.
      We also provide a qualitative analysis of abortion and contraceptive use based on
      in-depth interviews conducted in 2005 in Havana with 24 women who have had an
      abortion and 10 men whose partners have had an abortion. Information gained from
      a focus-group discussion with medical professionals also informed the study. Our
      four principal findings are: (a) longstanding awareness of abortion, (b) the view
      of abortion as a personal decision, (c) the influence of economic constraints on
      the decision to induce an abortion, and (d) general skepticism toward
      contraceptives. We discuss our results on abortion in Cuba in relation to the
      notion of social diffusion, an approach commonly used to explain the spread of
      fertility control throughout a population.

PMID- 19397183
TI  - Do women increase their use of reproductive health care when it becomes more
      available? Evidence from Indonesia.
AB  - Data from the Indonesia Family Life Survey are used to investigate the impact of
      a major expansion in access to midwifery services on women's use of antenatal
      care and delivery assistance. Between 1991 and 1998, Indonesia trained some
      50,000 midwives, placing them in poor communities that were distant from health
      care centers. We analyze information from pregnancy histories to relate changes
      in the choices that individual women make across pregnancies to the arrival of a
      trained midwife in the village. We show that regardless of a woman's educational
      level, the placement of village midwives in communities is associated with
      significant increases in women's receipt of iron tablets and in their choices
      about care during delivery--changes that reflect their moving away from reliance
      on traditional birth attendants. For women with relatively low levels of
      education, the presence of village midwives has the additional benefit of
      increasing use of antenatal care during the first trimester of pregnancy. The
      results of the study suggest that bringing services closer to women can change
      their patterns of use.

PMID- 19397184
TI  - Women's use of private and government health facilities for childbirth in
      Nairobi's informal settlements.
AB  - The private sector's role in increasing the use of maternal health care for the
      poor in developing countries has received increasing attention, yet few data
      exist for urban slums. Using household-survey data from 1,926 mothers in two
      informal settlements in Nairobi, Kenya, collected in 2006, we describe and
      examine the factors associated with women's use of private and government health
      facilities for childbirth. More women gave birth at private facilities located in
      the settlements than at government facilities, and one-third of the women gave
      birth at home or with the assistance of a traditional birth attendant. In
      multivariate models, women's education, ethnic group, and household wealth were
      associated with institutional deliveries, especially in government hospitals.
      Residents in the more disadvantaged settlement were more likely than those in the
      better-off settlement to give birth in private facilities. In urban areas,
      maternal health services in both the government and private sectors should be
      strengthened, and efforts made to reach out to women who give birth at home.

PMID- 19397185
TI  - Contraceptive use, birth spacing, and autonomy: an analysis of the Oportunidades
      program in rural Mexico.
AB  - Oportunidades, a conditional cash-transfer program instituted in Mexico in 1997,
      provides cash incentives to mothers to invest in the health and education of
      family members. Drawing from data gathered by Mexico's National Institute of
      Public Health, this study assesses the effect of the program on contraceptive use
      and birth spacing among titulares (female household heads) living in rural areas
      during the experimental period, 1998-2000, and during 2000-03, after
      incorporation of the control group. In 2000, titulares were more likely to use
      modern contraceptives than were women in the control group, although by 2003 all
      beneficiaries had the same probability of use. Change in autonomy was not a
      mediator, although baseline autonomy modified the program's influence on
      contraceptive use. Cox proportional hazard models produced estimates that birth
      spacing was similar between the beneficiaries and controls. Inconsistent findings
      may be the result of the way contraceptive use was defined in this study.
      Findings from this study may be useful for helping program planners better
      understand the role of conditional cash transfers in modifying family planning
      and fertility among poor rural women in Latin America.

PMID- 19397186
TI  - A framework of sexual partnerships: risks and implications for HIV prevention in
      Africa.
AB  - The global diversity of HIV epidemics can be explained in part by types and
      patterns of sexual partnerships. We offer a typology of sexual partnerships that
      corresponds to varying levels of HIV-transmission risk to help guide thinking
      about appropriate behavioral interventions, particularly in the epidemics of sub
      Saharan Africa. Declines in HIV prevalence have been associated with reductions
      in numbers of sex partners, whereas many other prevention strategies have not
      been demonstrated to reduce HIV transmission at a population level. We suggest a
      reorientation of current prevention efforts, based on the epidemiology of
      sexually transmitted HIV epidemics and trends in sexual behavior change.
      Concurrent sexual partnerships are likely to play a large role in transmission
      dynamics in the generalized epidemics of East and Southern Africa, and should be
      addressed through improved behavior-change interventions.

PMID- 19397187
TI  - Nepal 2006: results from the demographic and health survey.

PMID- 19397188
TI  - Swaziland 2006-07: results from the demographic and health survey.

PMID- 19397189
TI  - Mycobiota from Cyclamen persicum and its interaction with Botrytis cinerea.
AB  - Sixty-six fungi isolated from cyclamen phylloplanes were identified and assessed
      in vitro for antagonism to B. cinerea on leaves, petals, petioles and peduncles.
      The estimation of pathogen conidial production was used as indicator of
      biocontrol ability of each of the strains. They were classified by cluster
      analysis resulting in four categories according to their behavior in the
      different organs. The most promising category included 34 isolates that
      significantly reduced pathogen inoculum in all the organs. Correspondence
      analysis showed association among leaf isolations, strains of Clonostachys rosea
      and Penicillium spp. and the best biocontrol performance. The statistical
      analysis was successful in dealing with this complex set of experimental data.
      Leaf fungal diversity was higher than those of petals and petiols, with Shannon
      values of 2.7, 0.9 and 0.5 respectively. Evidence for antibiosis and
      hyperparasitism was found for C. rosea.

PMID- 19397190
TI  - Endomembrane system of aspen root cells plays a key role in defense against a
      common fungal root endophyte, Cryptosporiopsis radicicola.
AB  - The host-endophyte interaction between roots of aspen (Populus tremuloides) and
      Cryptosporiopsis radicicola was examined primarily by transmission electron
      microscopy. Hyphae growing on the exterior of the inoculated roots had a thick,
      electron-dense, adhesive sheath. At hyphal contact and penetration, host
      epidermal cells exhibited a series of defense responses (viz. formation of
      papillae and partition walls, general wall thickening and walling-off of internal
      hyphae). In papilla formation, loop-shaped, rough endoplasmic reticula (rER) gave
      rise to globose secretory vesicles that accumulated around and then fused to the
      developing papilla. Unlike papillae, general wall thickening was associated with
      the Golgi apparatus (GA) that produced cell wall materials; 1-3 layers of Golgi
      cisternae were in contact with or in the immediate proximity (mostly within 0-0.5
      microm) of and lying parallel to the host cell wall, where they budded out
      numerous subglobose vesicles that fused directly to the host cell wall and made
      it thicker. Partition wall formation and walling-off of internal hyphae also were
      common; the former was associated with an extended single cisterna, which was
      indistinguishable from rER or individual cisternae of GA, and in the latter
      phenomenon internal hyphae were encased by electron-dense material containing
      numerous ribosomes and membranous elements that were derived apparently from
      proliferated rER. These pronounced defense responses protected the stele and
      contributed to making C. radicicola endophytic rather than pathogenic.

PMID- 19397191
TI  - Spatial distribution of Neonectria species associated with beech bark disease in
      northern Maine.
AB  - Beech bark disease (BBD) requires prior infestation of bark by an exotic scale
      insect, Cryptococcus fagisuga, to permit infection by one or more fungi,
      primarily Neonectria ditissima and Neonectria faginata. Previous studies in North
      America report a progression in which N. faginata replaces N. ditissima as the
      dominant pathogen in the BBD complex. To examine the status of the Neonectria
      populations in forests that have developed for decades with and without BBD a
      survey was conducted 2005-2006 in northern Maine. Ascospore measurements from 201
      beech bark disks containing mature perithecia support reports that, once
      established, N. faginata dominates the BBD complex. However stands did contain
      more N. ditissima when other highly susceptible hardwood tree species were
      present (R2 = 0.775), regardless of disease severity. Abundance of N. ditissima
      in areas long affected by BBD suggests that N. ditissima, by continually
      supplying inocula from nonbeech hosts, continues to affect BBD.

PMID- 19397192
TI  - A new stromata-producing Neotyphodium species symbiotic with clonal grass
      Calamagrostis epigeios (L.) Roth. grown in China.
AB  - We describe a new stromata-producing Neotyphodium species symbiotic with clonal
      Calamagrostis epigeios (L.) Roth. Stromata on the grass, 47.5-186 mm long,
      occurred frequently, but neither perithecium nor mature ascus was observed.
      Morphology of fungal isolates obtained from symptomatic and asymptomatic tillers
      were identical to each other and similar to those of epichloe endophytes. In
      phylogenetic analysis all selected five fungal isolates clustered into a
      significantly distinct clade based on sequences of beta-tubulin gene (tubB)
      introns and translation elongation factor 1-alpha gene (tefA) introns with
      bootstrap values of 99%, supporting erection of a new species. Concerning the
      production of extremely long stromata on the host plants and absence of sexual
      spores, we propose the name Neotyphodium stromatolongum Y. Ji, L. Zhan et Z.
      Wang, sp. nov.

PMID- 19397193
TI  - Free-living fungal symbionts (Lepiotaceae) of fungus-growing ants (Attini:
      Formicidae).
AB  - Surveys of leucocoprinaceous fungi (Lepiotaceae, Agaricales, Basidiomycota) in
      the rainforests of Panama and Brazil revealed several free-living counterparts of
      fungi cultivated by primitive attine ants (the lower Attini, Formicidae,
      Hymenoptera), adding to two such collections identified in a survey by Mueller et
      al (1998). The accumulated evidence supports the hypothesis that perhaps all
      fungi of lower attine ants have close free-living relatives. Free-living
      counterparts of ant-cultivated fungi are collected most readily during the early
      rainy season; in particular these are free-living mushrooms of fungal
      counterparts that are cultivated as yeasts in gardens of ants in the Cyphomyrmex
      rimosus group. Free-living and symbiotic fungi of these yeast-cultivating ant
      species might represent a promising study system to compare the biology of
      sympatric, conspecific fungi existing outside versus inside the attine symbiosis.

PMID- 19397194
TI  - Taxonomy of Neotyphodium endophytes of Chinese native Roegneria plants.
AB  - In this study we describe a new Neotyphodium species, Neotyphodium sinicum, found
      in natural symbiosis with asymptomatic Roegneria spp. (Elymus spp.) native to
      China. We investigated the host specificity, morphology, mating compatibility and
      molecular phylogenetic evidence for recognition of this new species. N. sinicum
      is host specific and seedborne and widely distributed in China. Most
      morphological characteristics of this new species are typical of other
      Neotyphodium species, but the growth on PDA plates tends to be more rapid. Three
      of five N. sinicum strains examined had double alleles of tefA and two of the
      five strains had double alleles of both tubB and tefA. Phylogenetic relationships
      based on sequences of tubB introns and tefA introns revealed that the allele-1 of
      tefA and tubB clustered together in a distinct subclade in the Epichloe
      bromicola/E. yangzii clade. The allele-2 grouped in the Epichlok" typhina clade
      (ETC). N. sinicum therefore appears to be an interspecific hybrid related to both
      E. yangzii and members of ETC. In mating tests N. sinicum failed to hybridize
      with E. yangzii.

PMID- 19397195
TI  - Phytophthora x pelgrandis, a new natural hybrid pathogenic to Pelargonium
      grandiflorum hort.
AB  - A new Phytophthora hybrid of Ph. cactorum (Leb. & Cohn) Schroet. and Ph.
      nicotianaevan Breda de Haan pathogenic to cultivars of Pelargonium grandiflorum
      hort. is described as Phytophthora X pelgrandis and its morphological features
      are documented. Morphological, physiological (e.g., temperature requirements) and
      molecular data (DNA sequencing, random amplified polymorphic DNA-PCR) are
      presented for isolates of the Phytophthora hybrid. Pathogenicity was tested on
      cultivars of P. grandiflorum and Nicotiana tabacum. For comparison cultures of
      the parental species and additional Phytophthora taxa also were examined.

PMID- 19397196
TI  - Pythium delawarii--a new species isolated from soybean in Ohio.
AB  - A new species of Pythium isolated from soybean in Ohio is described. Pythium
      delawarii sp. nov. is characterized by globose internally proliferating
      sporangia, aplerotic oospores and diclinous antheridia that make broad lengthwise
      contact. Sporangia produce conspicuous papilla and germinate indirectly by
      producing zoospores via a vesicle and proliferate internally or the sporangia
      germinate directly with either one or more germ tubes. Pythium delawarii is
      pathogenic on soybean causing damping-off of seedlings. This oomycete can grow at
      10-34 C with an optimum of 28 C. The sequence of the ITS1, 5.8S and ITS2 region
      of the rDNA did not match the sequence of any known Pythium species but was
      similar to P. citrinum, P. litorale and P. sterilum. P. delawarii can be
      distinguished from these three species based on the presence of aplerotic
      oospores and diclinous antheridia and the absence of hypogynous antheridia.
      Therefore biological, morphological and molecular data support the recognition of
      a new species.

PMID- 19397197
TI  - Maravalia perae, a new species of rust fungus on Pera from Brazil.
AB  - A new species of rust fungus, Maravalia perae on Pera sp. (Euphorbiaceae), from
      Brazil is proposed. Spermogonia are type 5 and aeciospores and urediniospores are
      asymetrically obovoid to ellipsoid, with a concave side and 3(-4) equatorial germ
      pores. Teliospore walls are 2-5 pm thick at apex around the apical germ pore.
      This set of characters differentiates M. perae from other species of Maravalia. A
      revised key to all known Maravalia species, including the newly discribed
      species, is provided.

PMID- 19397198
TI  - Pseudobaeospora aphana, a new species from California.
AB  - Pseudobaeospora aphana, characterized by a brownish pileus with a lilac sheen,
      yellowish lamellae, a cutis of narrow hyphae on a subpellis of relatively wide
      and short cells, absence of cheilocystidia and color changes in KOH, and abundant
      clamp connections, is described as new. It was discovered during the Jan 2007
      Mycoblitz at Point Reyes National Seashore, the fourth such event in an ongoing
      effort to inventory the mycoflora of this national park.

PMID- 19397199
TI  - Glomus perpusillum, a new arbuscular mycorrhizal fungus.
AB  - A new arbuscular mycorrhizal fungal species of genus Glomus, G. perpusillum
      (Glomeromycota), forming small, hyaline spores is described and illustrated.
      Spores of G. perpusillum were formed in hypogeous aggregates and occasionally
      inside roots. They are globose to subglobose, (10-)24(-30) microm diam, rarely
      egg-shaped, oblong to irregular, 18-25 x 25-63 microm. The single spore wall of
      G. perpusillum consists of two permanent layers: a finely laminate, semiflexible
      to rigid outer layer and a flexible to semiflexible inner layer. The inner layer
      becomes plastic and frequently contracts in spores crushed in PVLG-based
      mountants and stains reddish white to grayish red in Melzer's reagent. Glomus
      perpusillum was associated with roots of Ammophila arenaria colonizing sand dunes
      of the Mediterranean Sea adjacent to Calambrone, Italy, and this is the only site
      of its occurrence known to date. In single-species cultures with Plantago
      lanceolata as host plant, G. perpusillum formed vesicular-arbuscular mycorrhiza.
      Phylogenetic analyses of partial SSU sequences of nrDNA placed the species in
      Glomus group A with no affinity to its subgroups. The sequences of G. perpusillum
      unambiguously separated from the sequences of described Glomus species and formed
      a distinct clade together with in planta arbuscular mycorrhizal fungal sequences
      found in alpine plants.

PMID- 19397200
TI  - Molecular and morphological evidence for the delimitation of Xylaria hypoxylon.
AB  - Xylaria hypoxylon, the type species of Xylaria (Xylariaceae, Sordariomycetes),
      was first described by Linnaeus as Clavaria hypoxylon from Sweden. Saccardo and
      other mycologists assumed a cosmopolitan distribution for this species. However,
      contradictory reports in the literature on its morphoanatomical characters and
      strongly inconsistent rDNA sequence data attributed to this species in GenBank
      suggested the existence of an unresolved species complex. To address this lack of
      clarity, molecular and morphological characters of numerous specimens and
      corresponding cultures of X. hypoxylon and related taxa from Europe were studied.
      Newly obtained 5.8S/ITS nrDNA sequence data were compared with published data and
      sequences of reference strains. European populations of X. hypoxylon from various
      hosts exhibited consistent rDNA sequence data and a relatively uniform
      holomorphic morphology, except for one specimen from Sweden that deviated in its
      ascospore morphology. Some samples from western United States showed DNA sequence
      data being identical to those of specimens from Europe, confirming a North
      American occurrence of X. hypoxylon. DNA sequences and morphology of other extra
      European material however showed substantial deviations. Definitely not
      conspecific with the European material examined in this study is a strain,
      assigned to X. hypoxylon, the DNA sequence data of which have been used in
      various phylogenetic studies as a representative of Xylariaceae and Xylariales
      respectively. This material probably represents X longiana.

PMID- 19397201
TI  - A new species of cellular slime mold from southern Portugal based on morphology,
      ITS and SSU sequences.
AB  - Sampling soils to look for dictyostelids in southern Portugal we found an isolate
      that has a morphology that differed from any previously described species of the
      group. We sequenced the internally transcribed spacer (ITS) and small subunit
      (SSU) genes of the nuclear ribosomal RNA and found that both sequences are
      distinct from all previously described sequences. Phylogenetic analyses place the
      new species in dictyostelid Group 3 (Rhizostelids) together with D. potamoides,
      with which it shares 65.8% identity for ITS and 96.6% for SSU. In this paper we
      describe a new species of cellular slime mold, Dictyostelium ibericum, based on
      morphological and molecular characters. It is a small species with polar granules
      in its spores.

PMID- 19397202
TI  - The sexual state of Aspergillus parasiticus.
AB  - The sexual state of Aspergillus parasiticus, a potent aflatoxin-producing fungus
      within section Flavi, is described. The production of nonostiolate ascocarps
      surrounded by a separate peridium within the stroma places the teleomorph in
      genus Petromyces. Petromyces parasiticus differs from P. alliaceus by its larger
      ascospores with finely tuberculate ornamentation. The anamorphic Aspergillus
      states of the two species differ in conidial head color and microscopic
      characters.

PMID- 19397203
TI  - [Expression of matrix metalloproteinase-3 after brain contusion in rats].
AB  - OBJECTIVE: To investigate the expression of matrix metalloproteinase-3 after
      brain contusion and its applicability for estimating the age of brain contusion.
      METHODS: Rats had been divided into three groups: control group, sham operation
      group and brain contusion group. The expression of matrix metalloproteinase-3 at
      different time was detected by immunohistochemistry and Western blot. RESULTS: By
      the immunohistochemistry, no staining was observed in control and sham operation
      groups. The positive staining of MMP-3 appeared 6 hours after contusion,
      increased gradually in 24 hours and peaked 5 days after contusion, then started
      to decrease, 14 days after contusion still could be observed. By the Western blot
      analysis, no expression of MMP-3 was detected in control and sham groups. The
      positive staining of MMP-3 appeared 6 hours after contusion, increased gradually
      and maximized 5 days after contusion, then started to decrease, 14 days after
      contusion still could be found. CONCLUSION: Time-order expression of MMP-3 could
      be used for estimating the age of brain contusion in forensic pathology.

PMID- 19397204
TI  - [Effects of curcumin on malondialdehyde and c-fos protein in hypoxia ischemia
      brain tissue in rats].
AB  - OBJECTIVE: To explore the effects of curcumin on the content of malondialdehyde
      (MDA) and the expression level of c-fos protein following hypoxia ischemia brain
      damage (HIBD) in rats. METHODS: Sprague-Dauley (SD) rats were randomly divided
      into four groups as the following: sham group, hypoxia ischemia brain damage
      group, curcumin group and solvent control group. The content of MDA in the brain
      was measured by colorimetry. The expression level of c-fos protein in the cortex
      tissue was detected by immunohistochemistry. Morphologic and structural changes
      of neuron cells of the cortex were observed by electron microscopy. RESULTS: The
      content of MDA was clearly lower in curcumin group than that in the other groups
      at the same time after HIBD. The expression level of c-fos protein was higher in
      the curcumin group than that in the other groups (P<0.05). Electron microscopy
      showed that the morphologic and structural changes of neuron cells of cortex in
      the curcumin group were reduced. CONCLUSION: Curcumin could significantly
      decrease the content of MDA, increase the expression level of c-fos protein and
      reduce the damage of the neuron cells.

PMID- 19397205
TI  - [Analysis of death caused by postpartum hemorrhage].
AB  - OBJECTIVE: To analyze the pathological characteristics and the death reasons due
      to postpartum hemorrhage, and to help to deal with the obstetrical medical
      tangles. METHODS: Thirty-two cases of death caused by postpartum hemorrhage
      encountered in our department since 1995 had been collected and retrospectively
      analyzed. RESULTS: Death caused by postpartum hemorrhage could be divided into
      single factor and multi-factor, with 81.25% due to single factor, 12.50% multi
      factor, and 6.25% unknown reason. The single factors included uterine atony,
      retained placenta, placenta increta, laceration of the lower genital tract, and
      coagulation defects. The multi-factor included a combination of two or more
      factors mentioned above. CONCLUSION: The causes of death due to postpartum
      hemorrhage should be analyzed according to the clinical characteristics of the
      postpartum hemorrhage and the autopsy examination.

PMID- 19397206
TI  - [Histopathological characterization of drug-related death].
AB  - OBJECTIVE: To study the histopathological changes in drug-related death cases in
      order to provide valuable information for its diagnosis. METHODS: Thirty cases of
      drug-related death were collected for systemic autopsy and histopathology
      examination. Ante mortem history and other informations of each case were also
      reviewed and analyzed. RESULTS: Injection marks, emaciation, asphyxia and
      histopathological changes in critical organs and tissues correlated with
      addiction behavior. In the 30 cases, 20% died of diseases, 33.3% acute drug
      intoxication, 26.7% quitting drug, 10% sudden death, and 10% outside violence.
      CONCLUSION: Systemic autopsy and histopathology examination in drug-related death
      are useful for determination of the cause of death in these cases.

PMID- 19397207
TI  - [The PRVEPs evoked by different fields stimulation].
AB  - OBJECTIVE: To study the character of the PRVEPs evoked by different stimulation
      fields in normal-vision subjects and its value in forensic medicine. METHODS: The
      PRVEPs were evoked by full-field, central-field and peripheral-field respectively
      in 30 subjects (60 eyes) and the latency and amplitude of N1 and P1 were
      analyzed. RESULTS: There was no statistically significant difference in the
      latency and amplitude of PRVEPs between right and left eyes. The appearance
      probability of all the waves was 100% at the different stimulations but that of
      N1 was 36.77% at the central-field. There was statistically significant
      difference in the latency of N1 at the full field and peripheral field
      stimulations and there was no statistically significant difference in the
      amplitude. There was statistically significant difference in the latency and
      amplitude of P1 at the full field, central field and peripheral field
      stimulation. CONCLUSION: The PRVEPs evoked by different field stimulations can be
      used to evaluate the functions of the different area retina and can be used to
      identify the exaggerated or pretended visual dysfunction.

PMID- 19397208
TI  - [Auditory P300 in the patients with traumatic brain injury].
AB  - OBJECTIVE: To assess the cognitive dysfunction in patients with the traumatic
      brain injury (TBI) by auditory P300. METHODS: Auditory P300 was recorded in the
      normal subjects and patients with TBI at the active (foot pedal) and passive
      task. RESULTS: In healthy persons, N2 and P3 in active task state showed higher
      amplitude than that in passive task state, and no significant prolongation of the
      latency. The amplitude of N1 and P2 at Cz was higher than that at Pz. In passive
      task state, N2 and P3 showed higher amplitude and longer latency in the patients
      than that in the healthy persons. N2 and P3 of the patients in the active task
      showed higher amplitude and longer latency than that in the passive task. Obvious
      change of P3 latency was observed in the patients with attention disorder.
      CONCLUSION: The type of task mainly affect the amplitude of N2 and P3. The
      latency of N2 and P3 in passive task can be used as an indication for evaluating
      cognitive function in patients with diffuse brain injury.

PMID- 19397209
TI  - [Civil competence assessment of the mental disorders involved in compensation of
      personal injury].
AB  - OBJECTIVE: To seek and ascertain indicators that can be used in the civil
      competence assessment of the mental disorders involved in compensation of
      personal injury. METHODS: A retrospective study was made on the data related to
      the interviewee's mental status assessed by forensic experts during the period
      from 2003 to 2005 in Institute of Forensic Science, Ministry of Justice,
      P.R.China. The 6 indicators, including awareness of situation, factual
      understanding of issues, appreciation of likely consequences, rational
      manipulation of information, functioning in one's own environment, and
      communication of choice, were graded and statistically analyzed using SPSS 11.5
      software. RESULTS: The 6 indicators correlated well with the assessment of
      forensic experts ,with the related coefficient between 0.632 and 0.876, and the
      inter-related coefficient among the 6 indicators between 0.575 and 0.911.
      CONCLUSION: The 6 indicators could be used for the civil competence assessment
      and may also be taken as the basis for further standardization and quantification
      of civil competence.

PMID- 19397210
TI  - [Assessment time on mental disability due to brain damage].
AB  - OBJECTIVE: To determine the best time for assessing mental disability due to
      brain damage. METHODS: Ninety-three mental disabilities due to brain damage in
      traffic accidents were assessed and their follow-up studies were taken in
      different period after the brain injury: 3 months, 6 months, 9 months and 12
      months. The patients' brain imaging, electroencephalogram (EEG) and detailed
      medical history were collected. Then to interview the patients' family members
      and to assess the patients' mental conditions with Wechsler Adult Intelligence
      Scale (WAIS), Social Disability Screening Schedule (SDSS), and Activity of Daily
      Living Scale (ADL). Diagnosis and disability assessments were based on all of the
      above information. RESULTS: ADL and SDSS had good distinction between different
      levels of disability and different time. The overall sample demonstrated that
      there was no statistically significant difference between patients' ADL and SDSS
      averages in 9 and 12 months. For mild disability, there was no statistically
      significant difference between ADL and SDSS averages in 6, 9 and 12 months. For
      moderate disability, there was no statistically significant difference between
      ADL and SDSS in 9 and 12 months. And there was no statistically significant
      difference between ADL and SDSS averages in 6, 9 and 12 months for severe
      disability. CONCLUSION: For mild disability, it is recommended to assess the
      mental disability 6 months after the injury, for moderate disability, it is 9
      months. The statistics data recommended that the best assessment time for severe
      disability is 6 months after injury. However, our comprehensive analysis
      concludes that the suitable time is 9 months after injury.

PMID- 19397211
TI  - [The degradation of housekeeping mRNA in dead rats by real-time RT-PCR].
AB  - OBJECTIVE: To explore the feasibility of real-time RT-PCR of housekeeping mRNA
      degradation in dead rats in order to seek new suitable techniques for post-mortem
      interval (PMI). METHODS: The levels of GAPDH mRNA and beta-actin mRNA in the
      brain and spleen of the rats were measured at different times after death by the
      SYBR Green I real-time RT-PCR. The relative mRNA level was indicated with the Ct
      value, then the relationship between the Ct value and PMI were analyzed and the
      corresponding regression equation was obtained. RESULTS: The Ct values of GAPDH
      mRNA and beta-actin mRNA by SYBR Green I real time RT-PCR correlated well with
      the PMI. CONCLUSION: The SYBR Green I real-time RT-PCR is a reliable technique
      for studying mRNA degradation. Adoption of the housekeeping genes eliminates
      systematical errors of other genes which have individual difference. As an
      objective and dynamic indication, Ct value has a good correlation with PMI, and
      could be applied for estimating PMI, especially in late period.

PMID- 19397212
TI  - [Determination of Cr, Cd, As, Tl and Pb in blood by inductively coupled plasma
      mass spectrometry].
AB  - OBJECTIVE: To establish an inductively coupled plasma mass spectrometry (ICP-MS)
      method for determination of Cr, Cd, As, Tl and Pb in blood. METHODS: The samples
      were digested by microwave digestion instrument. ICP-MS was applied to determine
      Cr, Cd, As, Tl and Pb in blood by using 115In as an internal standard. RESULTS:
      The limits of detection were in the range of 0.00001-0.00249 microg/L. The
      accuracy of the method ranged from 90.1% to 110.7% and the precision ranged from
      4.0% to 7.9%. CONCLUSION: The method is accurate and rapid with superior
      sensitivity and linear range. It could be used in the poisoning cases caused by
      Cr, Cd, As, Tl and Pb.

PMID- 19397213
TI  - [Improved nitric acid digestion method for detecting diatom in autopsy tissue].
AB  - OBJECTIVE: To investigate the advantages of nitric acid digestion method and its
      differences with the traditional method. METHODS: Ethanol was used to fully fix
      the testing sample. About 80-100 g of the testing samples were cut into pieces
      and digested with nitric acid. It was then centrifuged and washed to remove
      organic components. Smears were prepared and examined under the light microscope.
      RESULTS: The diatom had been identified with clear striations, counted
      conveniently and classified easily. CONCLUSION: The improved nitric acid
      digestion method is not only simple with a higher successful rate of detection,
      but also can prevent interference from contamination. It can improve the
      stability of the experimental results, avoid harm to human and environment, and
      provide higher safety in the course of experiment.

PMID- 19397214
TI  - [The application of three methods combined for extracting DNA from human
      epithelium].
AB  - OBJECTIVE: To improve DNA extraction from human epithelium. METHODS: Chelex-100,
      Chelex-100 organic combined and Chelex-100 magnetism pearl combined methods were
      adopted according to the situation of each case. RESULTS: With the stepwise
      extracting protocol, the trace amount of DNA was analyzed most efficiently and
      the success rate of DNA extracting was better improved. CONCLUSION: The
      efficiency of DNA extraction from human epithelium could be greatly improved by
      modifying the extracting protocol such as purification and concentration based on
      previous results.

PMID- 19397215
TI  - [Advances in the studies of postmortem interval estimation by the levels of
      chemical components in human vitreous humor after death].
AB  - Estimation of postmortem interval (PMI) is one of the problems that need to be
      solved for forensic examination of the dead body. Accurate estimation of PMI has
      great values to criminal investigation and trial. The levels of chemical
      components in human vitreous humor are changed with time after death, which can
      help estimate the PMI. The levels of certain chemical components, such as
      potassium, magnesium, ammonia, urea, creatinine, uric acid, hypoxanthine, lactic
      acid and so on, in human vitreous humor will gradually increase with time after
      death, while others such as calcium, sodium, enzymes, glucose, vitamin C and so
      on will decrease. The updates and advances in those studies were reviewed in this
      article.

PMID- 19397216
TI  - [Noncompaction of ventricular myocardium and its medicolegal evaluation].
AB  - Noncompaction of ventricular myocardium (NVM) is a rare cardiomyopathy. For the
      past few years, there have been more clinical reports and related scientific
      researches on NVM. It is one of the hottest topics in the field of clinical
      cardiovascular science. NVM is rare, but usually leads to fatal results, such as
      sudden unexpected death. Most forensic medical examiners in China have not
      recognized the importance of this disease. There are no good forensic
      pathological methods yet to identify this disease. Furthermore, NVM is easily to
      be confused with other types of heart diseases. As a result, we should be very
      careful about NVM, and understand the importance of making right diagnosis of
      NVM. This review focuses on NVM's pathological features, clinical diagnostic
      methods, and differential diagnosis from other cardiac disease. The key points on
      how to make right forensic pathological diagnosis of NVM have also been
      summarized.

PMID- 19397217
TI  - [Progress in individual identification of burned bones].
AB  - The burned bone DNA test have became more and more important in identifying the
      individuals and paternity involved in the fire, explosion disasters as well as
      burn corpse crimes. As an important genetic marker system, STR has been widely
      used in forensic individual identification, paternity test and other fields. In
      this article, the influence of burned temperature and time to STR typing was
      reviewed, the choice of STR locus and DNA extraction methods were discussed about
      burned bones.

PMID- 19397218
TI  - [Detection and application of ethyl glucuronide in forensic toxicology].
AB  - Ethyl glucuronide is a specific metabolite of ethanol. There have been plenty of
      articles referring its pharmacokinetics, detection and application as a specific
      bio-marker of alcohol intake. This article reviews various analytical methods of
      EtG, relationship between EtG quantification and ethanol intake, and criteria for
      determining chronic alcohol abuse, and origin of ethanol found in the cadavers by
      EtG analysis. EtG has its potential application in forensic toxicology.

PMID- 19397220
TI  - Relationship between incarceration frequency and human immunodeficiency virus
      risk behaviors of African American inmates.
AB  - OBJECTIVE: We examined the relationship between frequency of incarceration and
      preincarceration risk behaviors and determined the demographic factors associated
      with risk behaviors among a sample of African American inmates. METHODS: We
      surveyed 229 (102 female and 127 male) randomly selected inmates. Risk behaviors
      between inmates serving their first prison sentence and those who had been
      incarcerated in prison more than once were compared using the chi2 test.
      Multivariate logistic regression analysis was used to determine factors
      associated with risk behaviors. RESULTS: For most risk behaviors, there were no
      significant differences between inmates serving their first prison sentence and
      inmates incarcerated more than once; however, male inmates who had been
      incarcerated more than once were more likely to report having had multiple
      vaginal sex partners (OR, 2.42; 95% CI, 1.10-5.32; P = .03). No demographic
      variable was found to be independently associated with risk behaviors.
      CONCLUSIONS: Frequency of incarceration did not affect preincarceration human
      immunodeficiency virus (HIV) risk behaviors among this sample of African American
      inmates. HIV prevention efforts should be directed at addressing the individual
      and structural factors associated with high-risk behaviors among African
      Americans.

PMID- 19397221
TI  - Patterns in prostate-specific antigen test use and digital rectal examinations in
      the Behavioral Risk Factor Surveillance System, 2002-2006.
AB  - BACKGROUND: Studies have examined prostate-specific antigen (PSA) test and
      digital rectal examination (DRE) use among men; however, few have examined use of
      these procedures together over time. This study examined use of the PSA test and
      DRE among men over time and identified correlates associated with test use for
      the PSA test only, the DRE only, and both procedures combined. METHODS: The
      Behavioral Risk Factor Surveillance System (BRFSS) collected information on
      prostate cancer test use among 229,574 men aged 40 or older over 3 years (2002,
      2004, and 2006). Patterns of PSA test and DRE use were examined overall and by
      selected demographic and health-related characteristics. Correlates of recent PSA
      test and DRE use were determined using logistic regression. RESULTS: Overall
      trends for years 2002-2006 were a significant increase for PSA use only and a
      significant decrease of PSA and DRE use combined. Having had a recent PSA test
      (within 2 years) only; a recent DRE only; or both tests varied by
      sociodemographic and health-related variables, including age, race/ethnicity,
      marital status, levels of education and income, body mass index, health insurance
      status, and having a personal doctor or health care provider. CONCLUSION:
      Although major organizations are not in agreement about the efficacy of prostate
      cancer screening, the PSA test and DRE continue to be utilized regularly by a
      majority of American men over age 40. PSA test and DRE use in this population
      provide a basis for addressing issues related to screening.

PMID- 19397219
TI  - Irbesartan/hydrochlorothiazide for the treatment of isolated systolic
      hypertension: a subgroup analysis of the INCLUSIVE trial.
AB  - This post hoc analysis of the Irbesartan/Hydrochlorothiazide (HCTZ) Blood
      Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated
      the efficacy and safety of fixed-dose irbesartan/HCTZ in patients with isolated
      systolic hypertension. Adults with uncontrolled systolic blood pressure (SBP)
      (140-179 mm Hg; 130-179 mm Hg in type 2 diabetes) after 4 weeks or more of
      antihypertensive monotherapy once-daily treatment with placebo for 4-5 weeks,
      followed by HCTZ 12.5 mg for 2 weeks, irbesartan/HCTZ 150/12.5 mg for 8 weeks,
      and then irbesartan/HCTZ 300/25 mg for 8 weeks, in a prospective, multicenter,
      open-label, single-arm study. In patients with isolated systolic hypertension (n
      = 443) and the total study population (n = 736), irbesartan/HCTZ treatment for 16
      weeks provided comparable mean blood pressure (BP) reductions from baseline
      (21.4/10.1 mm Hg vs 21.5/10.4 mm Hg; p < .001 vs baseline) and high SBP control
      rates (74% vs 77%). Patients with isolated systolic hypertension and concomitant
      type 2 diabetes experienced smaller BP reductions (17.9/8.7 mm Hg vs 22.9/10.7 mm
      Hg) and lower rates of SBP control (< 130 mm Hg, 47%) than those without diabetes
      (< 140 mm Hg, 87%). BP reductions from baseline and SBP control rates were
      similar across isolated systolic hypertension subgroups (> or = 65 vs < 65 years,
      sex, race, and metabolic syndrome status). Irbesartan/HCTZ was well tolerated,
      with drug-related adverse events (dizziness, < or = 3%; upper respiratory tract
      infection, < or = 2%) occurring with similar rates in the isolated systolic
      hypertension and total population. Fixed-dose irbesartan/HCTZ combination
      treatment provided effective and well-tolerated BP lowering in a diverse
      population of patients with isolated systolic hypertension.

PMID- 19397222
TI  - Psychosocial factors influence parental decision for circumcision in pediatric
      males of African American descent.
AB  - BACKGROUND: The most recent policy statement by the American Academy of
      Pediatrics suggests there are insufficient data to recommend routine newborn
      circumcision. Nevertheless, circumcision rates have not declined in the United
      States. Some studies suggest that African Americans are less likely to be
      circumcised. In blacks that choose to circumcise their males, we sought to
      examine the factors that drive parents to favor circumcision. METHODS: The
      Parental Attitudes on Circumcision questionnaire was utilized to obtain
      demographic information and attitudinal responses to circumcision during urology
      clinic sessions at Howard University Hospital, a major teaching hospital located
      in an urban setting. Parents and caregivers of male children aged 3 months to 7
      years participated. Valid responses from 146 participants were collected.
      RESULTS: Ninety-six percent of our respondents believe that circumcision is
      healthy. Forty-one percent indicated health reasons as the most important
      influencing factor for choosing to circumcise their child, while 25% selected
      maternal preference. Eighty-one percent of all respondents indicated that 1 or
      more health care providers asked about their decision to circumcise their child.
      The mother was 12 times more likely than the father to make the final decision
      for circumcision, especially when her personal preference played a role. Eighty
      eight percent of respondents felt that circumcision is painful, but 87%
      considered the procedure safe, and another 72% believe that it is a necessary
      procedure. CONCLUSION: African American parents strongly believe that
      circumcision is essential for a healthy state and are willing to opt for the
      procedure despite the belief that it may be painful for the child. The mother
      primarily made the final decision to circumcise her child, largely based on the
      perceived health and hygiene benefits. In blacks, the mother yields considerable
      influence in the decision to circumcise the child, with maternal preference as
      the main reason for seeking circumcision in as much as a quarter of cases.

PMID- 19397223
TI  - Computed tomography imaging in the management of headache in the emergency
      department: cost efficacy and policy implications.
AB  - PURPOSE: To evaluate the economic impact and diagnostic utility of computed
      tomography (CT) in the management of emergency department (ED) patients
      presenting with headache and nonfocal physical examinations. METHODS AND
      MATERIALS: Computerized medical records from 2 major community hospitals were
      retrospectively reviewed of patients presenting with headache over a 2.5-year
      period (2003-2006). A model was developed to assess test outcomes, CT result
      costs, and average institutional costs of the ED visit. The binomial
      probabilistic distribution of expected maximum cases was also calculated.
      RESULTS: Of the 5510 patient records queried, 882 (16%) met the above criteria.
      Two hundred eighty-one patients demonstrated positive CT findings (31.8%), but
      only 9 (1.02%) demonstrated clinically significant results (requiring a change in
      management). Most positive studies were incidental, including old infarcts,
      chronic ischemic changes, encephalomalacia, and sinusitis. The average cost of
      the head CT exam and ED visit was $764 (2006 dollars). This was approximately 3
      times the cost of a routine outpatient visit (plus CT) for headache ($253). The
      incremental cost per clinically significant case detected in the ED was $50078.
      The calculated expected maximum number of clinically significant positive cases
      was almost 50% lower than what was actually detected. CONCLUSION: Our results
      indicate that emergent CT imaging of nonfocal headache yields a low percentage of
      positive clinically significant results, and has limited cost efficacy. Since the
      use of CT for imaging patients with headache in the ED is widespread, the
      economic implications are considerable. Health policy reforms are indicated to
      better direct utilization in these patients.

PMID- 19397224
TI  - Antioxidant therapy does not ameliorate oxidative stress and inflammation in
      patients with end-stage renal disease.
AB  - Oxidative stress and inflammation are common manifestations and major mediators
      of cardiovascular and many other complications of end-stage renal disease (ESRD).
      Oxidative stress and inflammation are intimately interrelated as each can cause
      the other. The present study tested the hypothesis that antioxidant therapy may
      alleviate oxidative stress and improve inflammation in ESRD patients. We studied
      37 hemodialysis patients, of whom 20 were treated daily with a combination of
      vitamin E, 800 lU; vitamin C, 250 mg; vitamin B6, 100 mg; vitamin B12, 250
      microg; and folic acid, 10 mg; whereas 17 patients were given placebo for 8
      weeks. Predialysis levels of f-2 isoprostane and protein carbonyl (markers of
      oxidative stress), C-reactive protein (CRP) and IL6 (markers/ mediators of
      inflammation) were measured prior to and at 4 and 8 weeks after the onset of
      therapy. Kt/V, predialysis and postdialysis blood pressure, blood hemoglobin,
      erythropoietin requirement, plasma ferritin and transferrin saturation, and
      nutritional indexes were similar among the 2 groups at baseline and remained
      virtually unchanged throughout the study period. Likewise, plasma f-2
      isoprostane, protein carbonyl, CRP, and IL-6 levels remained unchanged and were
      unaffected by antioxidant administration. In conclusion, the addition of a potent
      antioxidant cocktail to conventional vitamin supplements had no effect on
      severity of ESRD-induced oxidative stress, inflammation, hypertension, anemia, or
      nutritional disorders in hemodialysis patients. Thus, high doses of vitamins
      beyond the routinely prescribed vitamin supplements do not appear to be indicated
      in this population.

PMID- 19397225
TI  - Significance of bowel wall thickening on computed tomography scan: higher risk of
      pathology among African Americans compared to Hispanics.
AB  - PURPOSE: The aims of our study were to examine the role of colonoscopy as further
      workup for bowel wall thickening reported on computed tomography (CT) scans and
      to investigate whether there were significant differences in pathology found
      among the racial groups in our study population. METHODS: This is a retrospective
      study from March 2005 and January 2007 of all patients who have undergone
      colonoscopy for bowel wall thickening found on CT scans of the abdomen. RESULTS:
      Of 94 patients with bowel wall thickening on CT scans, 7 (8%) had adenocarcinoma,
      5 (5%) had large adenomas, 3 (3%) had infectious colitis, 2 (2%) ischemic
      colitis, 1 (1%) had inflammatory bowel disease, and 1 (1%) had a benign
      stricture. Bowel wall thickening on CT scan predicted clinical pathology in 34%
      of African Americans, as compared to 14% of Hispanics. Patients with significant
      pathology were more likely to have anemia and lower albumin levels. CONCLUSION:
      Patients with bowel wall thickening found on CT scans should be referred for
      colonoscopy, given that significant pathology is found in 20% of the cases.
      African Americans were 2.5 times more likely to have clinically significant
      pathology as compared to Hispanics.

PMID- 19397227
TI  - Laparoscopic cholecystectomy: analysis of 619 consecutive cases in a Caribbean
      setting.
AB  - INTRODUCTION: Laparoscopic cholecystectomy has become the gold standard in the
      definitive treatment of symptomatic gall bladder disease. It boasts superior
      morbidity and mortality and lower complication rates than open approaches. AIM:
      This study outlines the experiences associated with 619 laparoscopic
      cholecystectomies performed in Trinidad. METHODS: The records of 619 consecutive
      patients who underwent the procedure were reviewed. All cases were either
      performed or supervised by the senior author. The population comprised 511
      females and 108 males. The average age was 48.5 years. RESULTS: The commonest
      indications for surgery were symptomatic cholelithiasis (380 cases) and acute
      cholecystitis (111 cases). The mean operating time was 34 minutes. The mean
      length of stay on the ward was 17.45 hours. Mortality was zero. Only 4 cases were
      converted to open procedures. The commonest postoperative complication was wound
      infection. CONCLUSION: In summary, this study demonstrates that laparoscopic
      cholecystectomy can be performed safely in a Third World setting with results
      comparable to those internationally.

PMID- 19397226
TI  - Vitamin D deficiency is associated with worse cognitive performance and lower
      bone density in older African Americans.
AB  - BACKGROUND: Vitamin D deficiency is common in older adults and is more prevalent
      among persons with darker pigmented skin. The detrimental effects of vitamin D
      deficiency on the bone are widely known; however, recent data suggest that
      vitamin D deficiency may contribute to other disorders, including low mood,
      cognitive impairment, and impaired mobility. OBJECTIVE: The purpose of this study
      was to determine whether nonskeletal diseases such as depression, cognitive
      impairment, and physical disability, which have been associated with vitamin D
      deficiency, are more commonly seen in older African Americans. DESIGN: In a cross
      sectional study of 60 older adults (30 African Americans and 30 European
      Americans), vitamin D status, cognitive performance, physical performance, and
      bone mineral density (BMD) were assessed. Differences between groups and
      differences between those with vitamin D deficiency and those with normal vitamin
      D levels were tested. RESULTS: African Americans had a lower mean 25
      hydroxyvitamin D level (17.98 ng/ml; SD, 6.9) compared to European Americans
      (25.20 ng/ml; SD, 7.0; p < .0001). Participants with vitamin D deficiency
      performed worse on a measure of cognitive performance, the Short Blessed Test
      (10.87 vs 6.31; p = .016); the Physical Performance Test (PPT) (27.00 vs 28.96; p
      = .039); and had lower BMD (0.823 vs 0.914; p = .005) and t scores (-1.29 vs 
      0.72; p = .008) of the hip. Among African Americans, vitamin D deficiency was
      associated with worse cognitive performance and lower BMD of the hip.
      CONCLUSIONS: Vitamin D deficiency in older African Americans was associated with
      worse cognitive performance and lower BMD of the hip.

PMID- 19397228
TI  - The role of human immunodeficiency virus infection in infranuclear facial
      paralysis.
AB  - BACKGROUND: This study describes the pattern of idiopathic infranuclear facial
      palsy (facial neuropathy) and highlights the role of human immunodeficiency virus
      (HIV)/AIDS in its occurrence and management. PATIENTS AND METHODS: This study
      conducted in Ile-Ife, Nigeria, assessed individuals with idiopathic facial
      neuropathy seen at the neurology; maxillofacial surgery; and ear, nose and throat
      outpatient clinics between 1994 and 2006. RESULTS: Eighty-eight patients with
      idiopathic facial neuropathy were seen during the 13-year study period. Forty-six
      (52.3%) were males, and the age range was 15 to 76 years, with a median of 35.5
      years and interquartile range of 24.5 to 54 years. The right side was affected in
      59.1%, compared with 40.9% on the left side. Twenty-six patients (29.5%) were HIV
      positive at presentation: 16 males, 10 females; mean age for HIV-positive
      patients was 29.15 +/- 8.12 years and 44.39 +/- 18.48 years for HIV-negative
      patients. There was a significant relationship among the status of the patients
      and the severity at presentation (p = .035), treatment given (p = .019), and the
      occurrence of flu-like symptoms (p = .004). CONCLUSION: A high index of suspicion
      of seroconversion is essential in patients presenting with idiopathic facial
      neuropathy since it has implications for management. Serological testing for HIV,
      especially in patients at risk and those with history of recent flu-like
      symptoms, is recommended.

PMID- 19397229
TI  - Reactive arthritis associated with hidradenitis suppurativa.
AB  - This is a case report of a man with chronic hidradenitis suppurativa who
      developed reactive arthritis. He presented with swelling and pain in his larger
      joints, along with conjunctivitis involving his right eye. These symptoms
      coincided with a flare of the hidradenitis suppurativa. His clinical picture and
      laboratory findings were consistent with a diagnosis of reactive arthritis. He
      was initially treated with prednisone, and later with methotrexate, with
      improvement in his symptoms. This case report is a discussion of a rare cause of
      reactive arthritis. A review of the literature regarding this condition is also
      included.

PMID- 19397230
TI  - Transformation of adult myelodysplastic syndrome-refractory anemia to acute T
      cell lymphoblastic leukemia.
AB  - OBJECTIVE: Myelodysplastic syndrome (MDS) is recognized as a preleukemic disorder
      with a variable risk of transformation to acute myeloid leukemia. Usually the
      blast cells in leukemia are transformed after MDS displays a myeloid phenotype.
      Lymphoid progression had been reported as myeloid-lymphoid hybrid or early B
      phenotype, but our patient transformed acute T-lymphoblastic leukemia, which is a
      rare lymphoid transformation. CLINICAL PRESENTATION AND INTERVENTION: We present
      a case of refractory anemia with excess of blast that transformed into acute T
      cell lymphoblastic leukemia. MDS was diagnosed in a 69-year-old man in April
      2007. Twelve month later, he developed T-acute lymphoblastic leukemia. The blasts
      were positive for expression of CD2, CD3, CD5, CD7, CD45, and HLA-DR, leading to
      a diagnosis of T-lymphoblastic leukemia. The patient was treated with
      chemotherapy, but he died of multiple organ failure. CONCLUSION: The mechanism of
      lymphoid transformation is not yet fully understood. This case clinically
      supports the nature of MDS as a pluripotent hematopoietic stem cell disorder. MDS
      often transforms into acute leukemia, usually of a myeloid phenotype. The
      transformation of MDS into acute lymphoblastic leukemia is extremely rare.

PMID- 19397231
TI  - Reversible hyperglycemic homonymous hemianopia.
AB  - We report a 67-year-old female diabetic with homonymous hemianopia as the
      presenting sign of nonketotic hyperglycemia. Magnetic resonance imaging (MRI) was
      abnormal with diffuse bilateral hyperintense white matter changes. A follow-up
      MRI scan 15 years later showed persisting abnormality. Her hemianopic visual
      field loss was reversed after correction of her hyperglycemia. Diabetes mellitus
      should be considered with the sudden onset of a homonymous hemianopia.

PMID- 19397232
TI  - Good Samaritan Hospital and the North Carolina Medical College circa early 1900:
      the first major affiliation between a black hospital and a white medical college.

PMID- 19397233
TI  - Risa Lavizzo-Mourey, MD, MBA. Interview by George Anthony Dawson.

PMID- 19397234
TI  - White House version 2009.
AB  - With the parties' presidential nomination races down to the last few standing,
      what will the next U.S. Administration set as its legislative agenda? Considering
      the political and economic landscape, here's a look at the priorities that a
      newly occupied White House is likely to set--and what they could mean for home
      care and hospice.

PMID- 19397235
TI  - Legislative priorities 2008 National Association for Home Care and Hospice.
AB  - Home care and hospice providers seek a number of legislative reforms in order to
      more effectively address the challenges they face. Following are the top-ranked
      legislative priorities for 2008, along with specific recommendations on the
      issues, as chosen on by the membership of the National Association for Home Care
      & Hospice, and voted by its board of directors at its February 2008 meeting.

PMID- 19397236
TI  - 2008 a watershed year: hospice poised for change.

PMID- 19397237
TI  - Medicare provider enrollment update for home health agencies & hospices.

PMID- 19397238
TI  - NAHC celebrates its birthday and the beginning of its 27th year.

PMID- 19397239
TI  - Remembering Lillian Wald.

PMID- 19397240
TI  - Choosing a good death: palliative care options and legal requirements.

PMID- 19397241
TI  - Telecare: bridging the gap between technology and care.
AB  - Constance Clark is a 79-year-old widow who lives alone in what she describes as
      "the house that Jack built." Her husband "Jack" John Clark--Irishman, WWII
      veteran, handy man, craftsman, manufacturers' representative--started building
      their modest split-level house in a neighborhood of similar small homes when he
      returned from the Army in 1945.

PMID- 19397242
TI  - The right to die: 'do not resuscitate': the Terri Schiavo case. How does hospice
      fit in?
AB  - The life and death of Terri Schiavo left a legacy of increased awareness of the
      need for written directives for health care. Without advance directives,
      questions about decisions including guardianship, 'do not resuscitate', the use
      of artificial hydration and nutrition, and palliative sedation are suddenly
      important considerations. Because of her circumstances, "one of the most
      extensively litigated cases in the American judicial history ensued, leading to
      significant ethical, moral, religious, and legal issues". While the legal case
      was resolved after 15 years, questions remain with regard to the choices
      available for end-of-life care. What have we learned?

PMID- 19397243
TI  - Home care technology advocacy and the 110th Congress.

PMID- 19397244
TI  - President's Day?

PMID- 19397245
TI  - Five pillars of exceptional agencies.

PMID- 19397246
TI  - The CEO as a sales person.

PMID- 19397247
TI  - The three G's: Grassroots, Guerilla & Government.

PMID- 19397248
TI  - Six factors affecting your growth.

PMID- 19397249
TI  - Super Bowl celebrations.

PMID- 19397250
TI  - Political future of home care & hospice is bright.

PMID- 19397251
TI  - Spectroscopic study of tetradecyltrimethylammonium bromide Pt-C14TAB
      nanoparticles: structure and stability.
AB  - The vibrational spectra of platinum nanoparticles (12 nm) capped with
      tetradecyltrimethylammonium bromide, C(14)TAB, were investigated by Fourier
      transform infrared (FTIR) spectroscopy. We have shown that the thermal decay of
      Pt-C(14)TAB nanoparticles in N(2), H(2), and O(2) atmospheres leads to the
      release of the hydrocarbon chain of the surfactant and the formation of a
      strongly bonded layer of ammonium cations on the platinum surface. The platinum
      atoms accessible to CO chemisorption were not reducible by hydrogen in the
      temperature range from 30 to 200 degrees C. A FTIR spectrum of C(14)TAB adsorbed
      on Pt nanoparticles was dramatically perturbed as compared with pure C(14)TAB.
      New intense and broad bands centered at 1450 cm(-1) and 760 cm(-1) are making
      their appearance in Pt-C(14)TAB. It may be speculated that new bands are the
      result of coupling between conducting electrons of Pt and molecular vibrations of
      adsorbed C(14)TAB, and as a consequence, specific vibrational modes of ammonium
      cation are transformed into electron-vibrational modes.

PMID- 19397252
TI  - Morphology and mechanical properties of bicontinuous gels of agarose and gelatin
      and the effect of added lipid phase.
AB  - This study examines the structural properties of binary and tertiary mixtures
      made of the cold-setting biopolymers agarose and gelatin and a lipid phase with
      solid or liquid-like viscoelasticity. The working protocol included the
      techniques of small-deformation dynamic oscillation on shear, modulated
      differential scanning calorimetry and scanning electron microscopy, and
      theoretical modeling that adapted ideas of relating the morphology to the elastic
      modulus of synthetic polyblends and block polymers. The experimental setting was
      designed to encourage extensive phase separation in the binary gel of agarose and
      gelatin whose mechanical properties were rationalized on the basis of a
      bicontinuous blending law. The presence of two continuous phases allowed the
      slower-gelling component (gelatin) to exhibit favorable relative affinity for the
      solvent with increasing concentrations of the protein in the system. This is an
      unexpected outcome that contradicts the central finding of a single value of the
      p factor observed in the distribution of solvent between the continuous matrix
      and discontinuous inclusions of deswelled binary gels reported earlier in the
      literature. The incorporation of a lipid phase of effectively zero elastic
      modulus or in excess of 10(8) Pa in the composite aqueous gel weakens or
      reinforces the matrix accordingly. The elastic moduli and morphology of the
      tertiary blend were related to changing the relative phase volumes of components
      using analytical expressions of isotropically dispersed soft or rigid filler
      particles in a polymeric matrix.

PMID- 19397253
TI  - Comprehensive analysis of lipid dynamics variation with lipid composition and
      hydration of bicelles using nuclear magnetic resonance (NMR) spectroscopy.
AB  - Bicelles of various lipid/detergent ratios are commonly used in nuclear magnetic
      resonance (NMR) studies of membrane-associated molecules without the need to
      freeze the sample. While a decrease in the size (defined at a low temperature or
      by the q value) of a bicelle decreases its overall order parameter, the variation
      of lipid dynamics with a change in the lipid/detergent ratio is unknown. In this
      study, we report a thorough atomistic level analysis on the variation of lipid
      dynamics with the size and hydration level of bicelles composed of a
      phospholipid, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and a
      detergent, 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC). Two-dimensional
      (2D) separated-local-field NMR experiments were performed on magnetically aligned
      bicelles to measure (1)H-(13)C dipolar couplings, which were used to determine
      order parameters at various (head-group, glycerol, and acyl chain) regions of
      lipids in the bilayer. From our analysis, we uncover the extreme sensitivity of
      the glycerol region to the motion of the bicelle, which can be attributed to the
      effect of viscosity because of an extensive network of hydrogen bonds. As such,
      the water-membrane interface region exhibits the highest order parameter values
      among all three regions of a lipid molecule. Our experimental results demonstrate
      that the laboratory-frame 2D proton-detected-local-field pulse sequence is well
      suited for the accurate measurement of motionally averaged (or long-range) weak
      and multiple (1)H-(13)C dipolar couplings associated with a single carbon site at
      the natural abundance of (13)C nuclei.

PMID- 19397254
TI  - Structure, thermodynamics, and solubility in tetromino fluids.
AB  - To better understand the self-assembly of small molecules and nanoparticles
      adsorbed at interfaces, we have performed extensive Monte Carlo simulations of a
      simple lattice model based on the seven hard "tetrominoes", connected shapes that
      occupy four lattice sites. The equations of state of the pure fluids and all of
      the binary mixtures are determined over a wide range of density, and a large
      selection of multicomponent mixtures are also studied at selected conditions.
      Calculations are performed in the grand canonical ensemble and are analogous to
      real systems in which molecules or nanoparticles reversibly adsorb to a surface
      or interface from a bulk reservoir. The model studied is athermal; objects in
      these simulations avoid overlap but otherwise do not interact. As a result, all
      of the behavior observed is entropically driven. The one-component fluids all
      exhibit marked self-ordering tendencies at higher densities, with quite complex
      structures formed in some cases. Significant clustering of objects with the same
      rotational state (orientation) is also observed in some of the pure fluids. In
      all of the binary mixtures, the two species are fully miscible at large scales,
      but exhibit strong species-specific clustering (segregation) at small scales.
      This behavior persists in multicomponent mixtures; even in seven-component
      mixtures of all the shapes there is significant association between objects of
      the same shape. To better understand these phenomena, we calculate the second
      virial coefficients of the tetrominoes and related quantities, extract
      thermodynamic volume of mixing data from the simulations of binary mixtures, and
      determine Henry's law solubilities for each shape in a variety of solvents. The
      overall picture obtained is one in which complementarity of both the shapes of
      individual objects and the characteristic structures of different fluids are
      important in determining the overall behavior of a fluid of a given composition,
      with sometimes counterintuitive results. Finally, we note that no sharp phase
      transitions are observed but that this appears to be due to the small size of the
      objects considered. It is likely that complex phase behavior may be found in
      systems of larger polyominoes.

PMID- 19397255
TI  - Hydrogen bonding in ortho-substituted arylamides: the influence of protic
      solvents.
AB  - We combine molecular modeling and NMR methods to better understand intramolecular
      hydrogen bonding (H-bonding) in a frequently used arylamide foldamer building
      block, ortho-methoxy-N-methylbenzamide. Our results show that solvents have a
      profound influence on the cumulative number and stabilizing effects of
      intramolecular H-bonds, and thus conformational preferences, of foldamers based
      on this compound. While intramolecular H-bonds are conserved in aprotic
      environments, they are significantly disrupted in protic solvents. Furthermore,
      these solvent effects can be accurately quantified using the computational
      approach presented here. The results could have significant implications in
      foldamer design, particularly for applications in aqueous environments.

PMID- 19397256
TI  - Effect of alpha-cyclodextrin on drug distribution studied by electrochemistry at
      interfaces between immiscible electrolyte solutions.
AB  - The description and understanding of noncovalent interactions and distribution of
      potential new drug compounds in an organism is of paramount importance for the
      successful development of new drugs. In this work, a new procedure based on
      electrochemistry at the interface between two immiscible electrolyte solutions
      (ITIES) for addressing and discriminating between drug compound/ligand
      interactions in aqueous solution and nonspecific ligand effects on oil-water
      distribution behavior has been developed. The procedure is demonstrated using
      five drug compounds with different physical chemical parameters and alpha
      cyclodextrin as the aqueous phase ligand. Alpha-cyclodextrin was chosen as an
      aqueous phase ligand, as it is frequently used in drug formulations to enhance
      solubility and bioavailability of drug compounds. Supplementary capillary
      electrophoresis experiments provided more detailed information on alpha
      cyclodextrin drug complexation and, in combination with the electrochemical
      studies, provided information on solvation effects affecting the oil-water
      distribution of the drug compounds. The use of ligand shift ion partition
      diagrams for data presentation is a convenient format for the visualization of
      ligand effects on distribution behavior of related drug compounds.

PMID- 19397257
TI  - Amphiphilic random glycopolymer based on phenylboronic acid: synthesis,
      characterization, and potential as glucose-sensitive matrix.
AB  - This study is devoted to developing amphiphilic, random glycopolymers based on
      phenylboronic acid, which self-assemble to form nanoparticles (NPs), as a glucose
      sensitive agent. Maleimide-glucosamine was copolymerized with 3-acryl
      aminophenylboronic acid in methanol at 70 degrees C. Using the nanoprecipitation
      method, NPs with a narrow size distribution were successfully generated.
      Transmission electron microscopic analysis showed that the NPs were well
      dispersed as individual, spherically shaped particles. The swelling behavior of
      the NPs and the in vitro release profiles of insulin at different glucose
      concentrations revealed definite glucose sensitivity of the glycopolymers.
      Further, circular dichroism spectroscopy demonstrated that the overall tertiary
      structure of the released insulin was not altered compared with standard insulin.
      The analysis of relative cell proliferation suggested that the glycopolymer NPs
      had good biocompatibility. The glycopolymers that responded to changes in the
      glucose concentration of the surrounding environment are being aimed for use in
      self-regulated insulin delivery.

PMID- 19397258
TI  - Preparation of chitin nanofibers with a uniform width as alpha-chitin from crab
      shells.
AB  - Chitin nanofibers were prepared from dried crab shells by a simple grinding
      treatment in a never-dried state under an acidic condition after the removal of
      proteins and minerals. The obtained nanofibers were observed by FE-SEM and found
      to have a uniform width of approximately 10-20 nm and high aspect ratio; both
      these findings were similar to those for nanofibers from prawns. Furthermore, it
      was confirmed that the nanofibers were extracted from the natural
      chitin/protein/mineral composites of crab shell in their original state. That is,
      the N-acetyl group was not removed and the alpha-chitin crystal structure was
      maintained, as confirmed by elemental analysis data, FT-IR spectra, and X-ray
      diffraction profiles.

PMID- 19397259
TI  - Convenient access to biocompatible block copolymers from SG1-based aliphatic
      polyester macro-alkoxyamines.
AB  - SG1-based poly(d,l-lactide) (PLA) or poly(epsilon-caprolactone) (PCL) macro
      alkoxyamines were synthesized and further used as macroinitiators for nitroxide
      mediated polymerization (NMP) of 2-hydroxyethyl (meth)acrylate (HE(M)A) to obtain
      the corresponding PLA- or PCL-PHE(M)A block copolymers. First, a PLA-SG1 macro
      alkoxyamine was prepared by 1,2-intermolecular radical addition (IRA) of the MAMA
      SG1 (BlocBuilder) alkoxyamine onto acrylate end-capped PLA previously prepared by
      ring-opening polymerization. The NMP of HEA monomer from the PLA-SG1 macro
      alkoxyamine appeared to be well controlled in the presence of free SG1 nitroxide,
      contrary to that of HEMA. In the latter case, adjustable molecular weights could
      be obtained by varying the HEMA to macro-alkoxyamine ratio. The versatility of
      our approach was then further applied to the preparation of PHEMA-b-PCL-b-PHEMA
      copolymers from a alpha,omega-di-SG1 functionalized PCL macro-alkoxyamine
      previously obtained from a PCL diacrylate by IRA. Preliminary studies of
      neuroblast cultures on these PCL-based copolymer films showed acceptable cyto
      compatibility, demonstrating their potential for nerve repair applications.

PMID- 19397260
TI  - N-heterocyclic carbene-functionalized ruthenium phosphinidenes: what a difference
      a twist makes.
AB  - Catalyst tuning by changing ligands is a well-established protocol in transition
      metal chemistry. N-Heterocyclic carbenes (NHCs) and tertiary phosphines (R(3)P)
      are the ubiquitous ligand actors. Here we demonstrate that the relative sigma
      donor/pi-acceptor ability of the NHC ligand itself can be influenced by a simple
      substituent-controlled conformational change, thereby directly impacting the
      reactivity of the transition-metal complex.

PMID- 19397261
TI  - Characterization of beta-B-agostic isomers in zirconocene amidoborane complexes.
AB  - The reaction of Cp(x)(2)ZrCl(2) (Cp(x) = Cp, Cp*) with ammonia borane in presence
      of n-butyllithium yielded Cp(2)Zr(Cl)NH(2)BH(3) and Cp(x)(2)Zr(H)NH(2)BH(3).
      These derivatives are isoelectronic with the ethyl zirconocene chloride and
      hydride, respectively, and feature a chelating amidoborane ligand coordinating
      through a Zr-N bond and a Zr-H-B bridge. In solution, each of the complexes
      consists of an equilibrium mixture of two isomers differing in the orientation of
      the amidoborane ligand with respect to the Zr-X bond (X = H, Cl), while in the
      solid state, only one isomer was observed. Such isomers have not been
      characterized for any metal complexes containing the isoelectronic beta-agostic
      ethyl ligand or any other agostic alkyl group.

PMID- 19397262
TI  - Ligand-promoted carbene insertion into the aryl substituent of an N-heterocyclic
      carbene ligand in ruthenium-based metathesis catalysts.
AB  - Addition of L = carbon monoxide or aryl isocyanides to the Grubbs second
      generation carbene complexes Ru(H(2)IMes)(CHR)(PCy(3))Cl(2) (H(2)IMes = 1,3
      dimesityl-4,5-dihydroimidazol-2-ylidene; R = Ph, Me, H, CH=CMe(2)) triggers
      carbene insertion into an aromatic ring of the N-heterocyclic carbene supporting
      ligand, forming Ru{1-mesityl-3-(-7'-R-2',4',6'-trimethylcycloheptatrienyl)-4,5
      dihydroimidazol-2-ylidene}L(2)(PCy(3))Cl(2). Insertions are also promoted for
      other PR(3) substituted complexes by carbon monoxide and aryl isocyanides, and
      for the phosphine-free Hoveyda-Blechert complex Ru(H(2)IMes)(CH(i
      PrOC(6)H(4)))Cl(2) by aryl isocyanides and small phosphites but only after
      initial displacement of the coordinated ether. Heteroatom substituted carbenes do
      not undergo CO-promoted insertion unless poorer electron donor phosphine (PPh(3))
      and carbene (CH(OC(6)H(4)-p-NO(2)) ligands are both present. Insertion depends on
      the added ligand, the carbene substituent, and to a lesser degree on the PR(3)
      ligand trans to the N-heterocyclic carbene.

PMID- 19397263
TI  - Metabolism of flufenpyr-ethyl in rats and mice.
AB  - The metabolism of flufenpyr-ethyl [ethyl 2-chloro-5-[1,6-dihydro-5-methyl-6-oxo-4
      (trifluoromethyl)pyridazin-1-yl]-4-fluorophenoxyacetate] was examined in rats and
      mice. [Phenyl-(14)C]flufenpyr-ethyl was administered to rats and mice as a single
      oral dose at a level of 500 mg/kg, and (14)C-excretion was examined. Total (14)C
      recoveries within 7 days after administration were 93.2 to 97.5% (feces, 42.0 to
      46.0%; and urine, 47.2 to 55.5%) in rats and 92.6 to 96.4% (feces, 26.7 to 32.7%;
      and urine, 59.9 to 69.7%) in mice. (14)C-Excretion into expired air was not
      detected in rats (expired air of mice was not analyzed). No marked species- or
      sex-related differences were observed in the rate of (14)C-elimination, but a
      relatively higher excretion into the urine of mice was observed compared to that
      in rats. (14)C-residues in tissue 7 days after administration were relatively
      high for liver, hair, skin, and kidney, but total (14)C-residues were low, below
      0.2% of the dose. An ester cleaved metabolite (S-3153acid) was the major
      metabolite in feces and urine. Hydroxylation of the methyl group on the C5 of the
      pyridazine ring and ether cleavage were also observed. No sex-related differences
      were observed in (14)C-elimination, (14)C-distribution, and metabolite profiles,
      and metabolism of flufenpyr-ethyl in rats and mice was similar. In vitro
      metabolism of flufenpyr-ethyl was examined using stomach and intestinal contents
      and blood and liver S9 fractions (postmitochondrial supernatant fractions) in
      rats. S-3153acid was detected as a major metabolite in the presence of intestinal
      contents and blood and liver S9 fractions, and a small amount was also formed in
      the presence of stomach contents, indicating that the parent compound is rapidly
      metabolized by intestinal contents and blood and liver S9 fractions through ester
      cleavage.

PMID- 19397264
TI  - Determination of 5-hydroxymethylfurfural using derivatization combined with
      polymer monolith microextraction by high-performance liquid chromatography.
AB  - A simple and sensitive method for the determination of 5-hydroxymethylfurfural
      (HMF) in coffee, honey, beer, Coke, and urine by high-performance liquid
      chromatography (HPLC) is presented. This method is based on the formation of the
      2,4-dinitrophenylhydrazone of HMF and subsequent polymer monolith microextraction
      (PMME) of this derivative. A poly(methacrylic acid-co-ethylene glycol
      dimethacrylate) (MAA-co-EGDMA) monolithic capillary column was selected as the
      extraction medium. Several parameters affecting the derivatization of HMF with
      2,4-dinitrophenylhydrazine (DNPH) followed by extraction of the derivative were
      optimized. The procedure is simple and offers high sensitivity and specificity
      since the derivative of HMF is well preconcentrated by PMME with poly(MAA-co
      EGDMA) monolith and well separated from the other components of the samples under
      examination. The recoveries in coffee, honey, beer, Coke, and urine samples were
      in the range of 83.9-110.8% spiked at different levels with HMF. The inter- and
      intraday precisions were less than 10%. The LOD (S/N = 3) and LOQ (S/N = 10) for
      HMF were 1.0 ng/mL and 3.4 ng/mL, respectively.

PMID- 19397265
TI  - Dose-dependent absorption and metabolism of trans-polydatin in rats.
AB  - There is considerable evidence that stilbenes provide health benefits. trans
      Polydatin is one of the major stilbenoid compounds in red wine. The purpose of
      this study is to investigate the dose-dependent absorption and metabolism of
      trans-polydatin in rats. trans-Polydatin was administered to rats by gavage at
      three different doses (50, 100, and 300 mg x kg(-1)). Blood samples were then
      collected at different time points. In situ perfusion of rat small intestine and
      liver was used to investigate the first-pass metabolism of trans-polydatin. trans
      Polydatin and its metabolites were detected by LC-MS/MS. trans-Polydatin and its
      metabolites resveratrol, glucuronidated resveratrol, and glucuronidated trans
      polydatin were detected in plasma within 10 min following oral administration of
      trans-polydatin; in situ perfusion of the rat small intestine and liver with
      trans-polydatin yielded the same result. The AUC(0-infinity) of trans-polydatin
      and its metabolites increased in a dose dependent manner following oral
      administration of trans-polydatin. This indicates that in the rats, trans
      polydatin is absorbed in a dose-dependent manner and undergoes extensive first
      pass deglycosylation and glucuronidation. Orally administered trans-polydatin,
      therefore, is metabolized primarily to resveratrol in the small intestine and
      liver, where it is further metabolized to the glucuronidated resveratrol.

PMID- 19397266
TI  - Identification of oligosaccharides formed during stachyose hydrolysis by Pectinex
      Ultra SP-L.
AB  - The commercial enzyme preparation Pectinex Ultra SP-L containing
      fructosyltransferase activity was used to hydrolyze stachyose. During this
      reaction, besides the formation of mono-, di-, and trisaccharides (DP(3)), the
      presence of one pentasaccharide (DP(5)) and a new oligosaccharide (DP(6)) has
      been detected by gas chromatography. DP(5) and DP(6) oligosaccharides were
      isolated and fully characterized for the first time by an extensive nuclear
      magnetic resonance (NMR) study. Complete structure elucidation and full proton
      and carbon assignments were carried out using 1D ((1)H, (13)C) and 2D (gCOSY,
      multiplicity-edited gHSQC, gHSQC-TOCSY, and gHMBC) NMR experiments. The two
      oligosaccharides were shown to be stachyose-based structures; the pentasaccharide
      has a fructose unit linked to the C-1 of the fructose end of stachyose, and the
      hexasaccharide has a fructose unit linked to the C-1 of the fructose end of the
      pentasaccharide. The fructosyltransferase activity present in Pectinex Ultra SP-L
      allows new uses of this commercial enzyme preparation in the synthesis of
      oligosaccharides derived from alpha-galactosides.

PMID- 19397267
TI  - Winter/spring changes in fatty acid composition of farmhouse Idiazabal cheese due
      to different flock management systems.
AB  - Typically, two different flock managements are employed by basque sheepherders in
      winter and spring. Thus, seasonal changes in the fatty acid (FA) composition of
      Idiazabal PDO farmhouse cheeses were studied. Ewe's raw milk cheeses elaborated
      in winter and spring were collected after 120 days of ripening from 10 Idiazabal
      PDO farmhouses. In winter, concentrate and conserved forages were fed, whereas a
      part-time grazing system was adopted from spring onward. Spring cheeses had less
      (P <or= 0.05) saturated FA and higher (P <or= 0.05) content of unsaturated FA,
      including trans-FA (mainly trans-vaccenic acid) and conjugated linoleic acid
      (CLA), branched-chain FA (BCFA), and n-3 FA. Principal component analysis (PCA)
      separated winter and spring cheeses into two groups by the combination of two
      principal components (84.2% of variance). Fresh pasture in the diet enhanced
      desirable FA and lowered atherogenicity index in cheeses, supporting the benefits
      of using a part-time grazing system for the consumer.

PMID- 19397268
TI  - Rational design and synthesis of highly potent pharmacological chaperones for
      treatment of N370S mutant Gaucher disease.
AB  - Highly potent N-substituted delta-lactams have been rationally designed and
      synthesized by a concise route with a one-pot tandem reaction as key step. These
      iminosugars show weak inhibition of wild-type beta-glucocerebrosidase but 3- to 6
      fold increases in mutant enzyme activity (N370S).

PMID- 19397269
TI  - Structure-guided design, synthesis, and evaluation of salicylic acid-based
      inhibitors targeting a selectivity pocket in the active site of human 20alpha
      hydroxysteroid dehydrogenase (AKR1C1).
AB  - The first design, synthesis, and evaluation of human 20alpha-hydroxysteroid
      dehydrogenase (AKR1C1) inhibitors based on the recently published crystal
      structure of its ternary complex with inhibitor are reported. While the enzyme
      inhibitor interactions observed in the crystal structure remain conserved with
      the newly designed inhibitors, the additional phenyl group of the most potent
      compound, 3-bromo-5-phenylsalicylic acid, targets a nonconserved hydrophobic
      pocket in the active site of AKR1C1 resulting in 21-fold improved potency (K(i) =
      4 nM) over the structurally similar 3alpha-hydroxysteroid dehydrogenase isoform
      (AKR1C2). The compound is hydrogen bonded to Tyr55, His117, and His222, and the
      phenyl ring forms additional van der Waals interactions with residues Leu308,
      Phe311, and the nonconserved Leu54 (Val in AKR1C2). Additionally, the metabolism
      of progesterone in AKR1C1-overexpressed cells was potently inhibited by 3-bromo-5
      phenylsalicylic acid, which was effective from 10 nM with an IC(50) value equal
      to 460 nM.

PMID- 19397270
TI  - Discovery and biological evaluation of novel cyanoguanidine P2X(7) antagonists
      with analgesic activity in a rat model of neuropathic pain.
AB  - We disclose the design of a novel series of cyanoguanidines that are potent
      (IC(50) approximately 10-100 nM) and selective (> or = 100-fold) P2X(7) receptor
      antagonists against the other P2 receptor subtypes such as the P2Y(2), P2X(4),
      and P2X(3). We also found that these P2X(7) antagonists effectively reduced
      nociception in a rat model of neuropathic pain (Chung model). Particularly,
      analogue 53 proved to be effective in the Chung model, with an ED(50) of 38
      micromol/kg after intraperitoneal administration. In addition compound 53
      exhibited antiallodynic effects following oral administration and maintained its
      efficacy following repeated administration in the Chung model. These results
      suggest an important role of P2X(7) receptors in neuropathic pain and therefore a
      potential use of P2X(7) antagonists as novel therapeutic tools for the treatment
      of this type of pain.

PMID- 19397271
TI  - (Z)- and (E)-2-(1,2-dihydroxyethyl)methylenecyclopropane analogues of 2'
      deoxyadenosine and 2'-deoxyguanosine. Synthesis of all stereoisomers, absolute
      configuration, and antiviral activity.
AB  - Chiral Z- and E-stereoisomers of (1,2-dihydroxyethyl)methylenecyclopropane
      analogues of 2'-deoxyadenosine and 2'-deoxyguanosine were synthesized, and their
      antiviral activity was investigated. (S)-Methylenecyclopropylcarbinol (16) was
      converted in seven steps to reagents 26 and 27, which were used for alkylation
      elimination of adenine and 2-amino-6-chloropurine to get ultimately analogues
      12a, 12b, 13a, 13b, 14a, 14b, 15a, and 15b. The enantiomeric series ent-12a, ent
      12b, ent-13a, ent-13b, ent-14a, ent-14b, ent-15a, and ent-15b was obtained by
      similar procedures starting from (R)-methylenecyclopropylcarbinol (ent-16). The Z
      isomer ent-12b was an inhibitor of two strains of human cytomegalovirus (HCMV)
      with EC(50) of 6.8 and 7.5 microM and of murine cytomegalovirus (MCMV) with
      EC(50) of 11.3 microM. It was less active against HCMV with mutated gene UL97. It
      inhibited Epstein-Barr virus (EBV) with EC(50) of 8 microM. The E-isomers ent
      15a, ent-13a, and 15b were less effective. All adenine analogues with the
      exception of the Z-isomers ent-12a and ent-14a were moderate substrates for
      adenosine deaminase.

PMID- 19397272
TI  - Modified capillary cell for foam film studies allowing exchange of the film
      forming liquid.
AB  - Many of the macroscopic properties of foams and emulsions are controlled by the
      mesoscopic properties of the thin films separating the bubbles or droplets. The
      properties of these films depend on contributions (1) from the adsorbed surface
      layers and (2) from the liquid that separates these adsorbed layers. To separate
      in the experimental studies the effects of these two contributions, we developed
      a new modified version of the capillary cell for foam film studies (originally
      developed by Scheludko and Exerowa (Scheludko, A.; Exerowa, D. Kolloid Z. 1959,
      165, 148-151), which allows exchange of the film-forming liquid between the air
      water surfaces. This modified cell allows one to distinguish between the role of
      the adsorbed species (e.g., proteins, particles, or long-chain synthetic
      polymers) and the species present in the film interior (e.g., particles,
      electrolytes, or surfactants). The film properties that can be studied in this
      way include film stability, rate of film thinning, and surface forces stabilizing
      the film. These properties are of significant interest in understanding and
      controlling the stability of dispersed systems. The experimental procedure and
      the capabilities of the modified cell are demonstrated in several examples.

PMID- 19397273
TI  - Raman study of the puroindoline-a/lysopamitoylphosphatidylcholine interaction in
      free standing black films.
AB  - The conformation of puroindoline-a (PIN-a), a protein extracted from wheat
      endosperm, in free-standing black films has been studied using confocal Raman
      spectroscopy. This protein is characterized by the presence in its sequence of a
      unique tryptophan (Trp)-rich domain and of five disulfide bridges stabilizing its
      three-dimensional structure. PIN-a is able to form free-standing films, which are
      very stable in time, because of its remarkable surface-active properties. These
      films become black in a few hours and are characterized by the presence of
      numerous aggregates. Their Raman spectra show major modifications of the PIN-a
      structure as compared to the solid form, such as the formation of beta-sheets or
      unordered structures, the modification of the environment of the Trp domain and,
      the conformation of disulfide bridges. These modifications are in agreement with
      an unfolding of the protein at the interfaces of the film and suggest that the
      Trp domain is involved in the aggregation. We have also studied the influence of
      increasing amounts of lysopalmitoylphosphatidylcholine (LPC) into the films. The
      direct observation of these mixed films shows that LPC inhibits the formation of
      PIN-a aggregates and that the conformation of PIN-a is strongly correlated to the
      LPC/PIN-a molar ratio. Raman spectroscopy also shows that PIN-a disturbs the
      highly organized arrangement of LPC molecules in the film.

PMID- 19397275
TI  - Better than random? The chemotype enrichment problem.
AB  - Chemotype enrichment is increasingly recognized as an important measure of
      virtual screening performance. However, little attention has been paid to
      producing metrics which can quantify chemotype retrieval. Here, we examine two
      different protocols for analyzing chemotype retrieval: "cluster averaging", where
      the contribution of each active to the scoring metric is proportional to the
      number of other actives with the same chemotype, and "first found", where only
      the first active for a given chemotype contributes to the score. We demonstrate
      that this latter analysis, common in the qualitative analysis used in the current
      literature, has important drawbacks when combined with quantitative metrics.

PMID- 19397274
TI  - The structure of the active site H-cluster of [FeFe] hydrogenase from the green
      alga Chlamydomonas reinhardtii studied by X-ray absorption spectroscopy.
AB  - The [FeFe] hydrogenase (CrHydA1) of the green alga Chlamydomonas reinhardtii is
      the smallest hydrogenase known and can be considered as a "minimal unit" for
      biological H(2) production. Due to the absence of additional FeS clusters as
      found in bacterial [FeFe] hydrogenases, it was possible to specifically study its
      catalytic iron-sulfur cluster (H-cluster) by X-ray absorption spectroscopy (XAS)
      at the Fe K-edge. The XAS analysis revealed that the CrHydA1 H-cluster consists
      of a [4Fe4S] cluster and a diiron site, 2Fe(H), which both are similar to their
      crystallographically characterized bacterial counterparts. Determination of the
      individual Fe-Fe distances in the [4Fe4S] cluster ( approximately 2.7 A) and in
      the 2Fe(H) unit ( approximately 2.5 A) was achieved. Fe-C( horizontal lineO/N)
      and Fe-S bond lengths were in good agreement with crystallographic data on
      bacterial enzymes. The loss of Fe-Fe distances in protein purified under mildly
      oxidizing conditions indicated partial degradation of the H-cluster. Bond length
      alterations detected after incubation of CrHydA1 with CO and H(2) were related to
      structural and oxidation state changes at the catalytic Fe atoms, e.g., to the
      binding of an exogenous CO at 2Fe(H) in CO-inhibited enzyme. Our XAS studies pave
      the way for the monitoring of atomic level structural changes at the H-cluster
      during H(2) catalysis.

PMID- 19397276
TI  - Proteomic analysis reveals multiple patterns of response in cells exposed to a
      toxin mixture.
AB  - We have used proteomic analyses to probe the responses induced by a pair of
      marine biotoxins, okadaic acid (OA) and gambierol (GB), added alone or in
      combination to a cultured cell line and carried out a preliminary investigation
      into the possible interactions between toxins possessing two different molecular
      mechanisms of action at a cellular level. When MCF-7 cells were treated with OA,
      we found that cellular levels of 30 proteins were significantly affected,
      including several isoforms of nonphosphorylated and phosphorylated hsp 27, as
      well as enzymes involved in the maintenance of nucleoside triphosphate pools and
      the control of redox states of the cell. When we repeated our analysis using GB,
      nine proteins were significantly affected, including some isoforms of
      nonphosphorylated hsp 27, as well as semenogelin-1, myosin-7, and the ATP
      synthase subunit delta. The combined addition of OA and GB to MCF-7 cells, in
      turn, affected 14 proteins, including some isoforms of nonphosphorylated and
      phosphorylated hsp 27, as well as myosin-7, the ATP synthase subunit delta, and
      enzymes involved in the control of redox states of the cell. If components
      affected by either OA or GB, as well as by the combined treatment, were
      classified according to the detected changes, two sets of data were obtained,
      including the components whose levels were found affected by the combined
      treatment, regardless of the effect observed after addition of only one agent,
      and those that had been found affected in cells that had been challenged with
      only one toxin but not when cells had been subjected to the combined treatment.
      Multiple patterns of responses to the toxin mixture were recorded in the two
      sets, consisting of both independent and interacting actions, among which we
      detected synergistic, similar, and antagonistic effects.

PMID- 19397277
TI  - 4'-Epidoxorubicin to re-explore anthracycline degradation in cardiomyocytes.
AB  - Cardiotoxicity limits the clinical use of doxorubicin (DOX) and other quinone
      hydroquinone antitumor anthracyclines. One-electron reduction of the quinone
      moiety is followed by the formation of reactive oxygen species (ROS) that have
      been proposed to induce cardiotoxicity through an oxidative stress; conversely,
      one-electron oxidation of the hydroquinone moiety by hydrogen peroxide (H(2)O(2))
      and oxyferrous myoglobin (Mb(II)O(2)) is followed by an anthracycline degradation
      process that has been proposed to limit cardiotoxicity. We previously reported
      that tert-butoxycarbonyl-alanine (t-BA) impeded DOX oxidation/degradation by
      H(2)O(2)/Mb(II)O(2) in a cell-free system; accordingly, t-BA increased the levels
      of DOX, its conversion to ROS, and its concentration-related toxicity in
      cardiomyocytes. To re-explore methodological and toxicological aspects of
      anthracycline degradation, we used 4'-epidoxorubicin (EPI), an anthracycline
      analogue that is very similar to DOX but undergoes protonation-sequestration in
      cytoplasmic acidic organelles. t-BA lacked an effect on H9c2 cardiomyocytes
      exposed to EPI; however, blocking the protonation-sequestration mechanism with
      the vacuolar H(+)-ATPase inhibitor, bafilomycin A1 (BFL), enabled t-BA to
      increase the cellular levels of EPI, its conversion to ROS, and its concentration
      related toxicity. This suggested that t-BA was specific enough to increase the
      cellular levels and toxicity of only those anthracyclines that were liable to
      oxidation/degradation by H(2)O(2)/Mb(II)O(2). By exposing cardiomyocytes to
      nontoxic concentrations of DOX or EPI and by increasing their cellular levels by
      means of appropriate combinations with t-BA, BFL, or t-BA+BFL, we nonetheless
      found that the loss of cardiomyocyte viability correlated with the accumulation
      of undegraded anthrayclines but not with their ability to form ROS or to induce
      lipid peroxidation. This suggested that an accumulation of undegraded
      anthracyclines might induce cardiotoxicity also by mechanisms independent of ROS
      and oxidative stress. Thus, EPI proved useful to refine the value of t-BA in the
      studies of anthracycline degradation and to reappraise the role of anthracycline
      degradation in cardiotoxicity.

PMID- 19397278
TI  - Size effect of Pt nanoparticle on catalytic activity in oxidation of methanol and
      formic acid: comparison to Pt(111), Pt(100), and polycrystalline Pt electrodes.
AB  - This work presents variation of oxidative catalytic activities of methanol and
      formic acid on Pt nanoparticles of various sizes and a comparison to the results
      observed on Pt(111), Pt(100), and polycrystalline Pt. The Pt nanoparticles
      dispersed on platelet carbon nanofiber are cuboctahedral particles, whose sizes
      span from 5.6 to 1.1 nm. The electrochemically active surface areas, measured
      using charges of hydrogen adsorption/desorption and stripping of adsorbed CO, are
      reasonably consistent with those calculated theoretically with a simple
      cuboctahedron model. However, Pt nanoparticles with extremely small size (<1.8
      nm) aggregate to reduce their surface areas. The size effect of Pt nanoparticles
      in oxidation of methanol and formic acid is discussed in terms of specific
      activity (current per unit surface area) and mass activity (current per unit
      mass).

PMID- 19397279
TI  - Redox-dependent conformational changes in cytochrome C oxidase suggest a gating
      mechanism for proton uptake.
AB  - A role for conformational change in the coupling mechanism of cytochrome c
      oxidase is the subject of controversy. Relatively small conformational changes
      have been reported in comparisons of reduced and oxidized crystal structures of
      bovine oxidase but none in bacterial oxidases. Comparing the X-ray crystal
      structures of the reduced (at 2.15 A resolution) and oxidized forms of cytochrome
      c oxidase from Rhodobacter sphaeroides, we observe a displacement of heme a(3)
      involving both the porphyrin ring and the hydroxyl farnesyl tail, accompanied by
      protein movements in nearby regions, including the mid part of helix VIII of
      subunit I which harbors key residues of the K proton uptake path, K362 and T359.
      The conformational changes in the reduced form are reversible upon reoxidation.
      They result in an opening of the top of the K pathway and more ordered waters
      being resolved in that region, suggesting an access path for protons into the
      active site. In all high-resolution structures of oxidized R. sphaeroides
      cytochrome c oxidase, a water molecule is observed in the hydrophobic region
      above the top of the D path, strategically positioned to facilitate the
      connection of residue E286 of subunit I to the active site or to the proton
      pumping exit path. In the reduced and reduced plus cyanide structures, this water
      molecule disappears, implying disruption of proton conduction from the D path
      under conditions when the K path is open, thus providing a mechanism for
      alternating access to the active site.

PMID- 19397280
TI  - Self-organized hierarchical structures in polymer surfaces: self-assembled
      nanostructures within breath figures.
AB  - Herein we report the preparation of hierarchically micro- and nanostructured
      polymer surfaces in block copolymer/homopolymer blends. The structural order at
      different length scales was obtained combining two methodologies, e.g., the
      breath figures method to produce porous microstructures ("top-down" approach)
      with block copolymer self-assembly to induce microphase separation at the
      nanometer length scale ("bottom-up" approach). The interplay of the breath figure
      formation during the spin-coating and self-assembly of the triblock copolymer
      allowed the preparation of polymer surfaces having micrometer-sized cavities
      decorated with nanostructured block copolymers. The system described herein
      possesses unique characteristics. First, the surface chemical composition can be
      varied by a surface rearrangement upon annealing either to dry or humid air.
      Moreover, surface rearrangement is accompanied with structural changes, i.e. both
      topography and nanostructuration can be reversibly modified upon annealing. In
      terms of topograghy, a transition between holes and hills was obtained upon soft
      annealing to water vapor and can be recovered upon annealing to dry air. Finally,
      the pore nanostructure can be modulated from a micellar array to a lamellar phase
      when the film is exposed either to air or to tetrahydrofuran vapor.

PMID- 19397283
TI  - Identification of immunogenic antigen candidate for Chlamydophila pneumoniae
      diagnosis.
AB  - Chlamydophila pneumoniae is a Gram-negative intracellular obligate human pathogen
      and accounts for 5-10% of cases of community-acquired pneumonia. However,
      isolating and culturing this pathogen is difficult, so there have been several
      studies searching for new biomarkers for its diagnosis. In this study, we
      obtained immunogenic proteins of C. pneumoniae KNIH-1 for diagnosis using
      immunoproteomics. C. pneumoniae infection sera were selected for the highest
      index value of C. pneumoniae-specific IgG using microimmunofluorescence (MIF).
      The detected protein spots in common from C. pneumoniae infection sera using
      proteome analysis were identified as Omp11, type III secretion system ATPase, and
      PmpG by LC-MS/MS and MS databases. They were selected as candidate antigens. In
      addition, using in silico prediction we also identified proteins encoded by
      Omp11, PmpG and IncA as antigens. And then, IncA acts as an effector by a type
      III secretion system ATPase, as identified by mass spectrometry, and was selected
      as a candidate antigen. Thus, we predict proteins encoded by Omp11, the PmpG
      family and by IncA as candidate diagnostic immunogens.

PMID- 19397284
TI  - Iron(II) complexes with redox-active tetrazene (RNNNNR) ligands.
AB  - This paper describes the redox chemistry of a tetrazene ligand on (beta
      diketiminato)iron complexes. Addition of 1-adamantyl azide to an iron(I) source
      gives the tetrazene complex L(Me)Fe(AdNNNNAd), most likely through an
      imidoiron(III) intermediate. Spectroscopic, magnetic, crystallographic, and
      computational investigations of the tetrazene complex show that one unpaired spin
      occupies a primarily ligand-based orbital, and is antiferromagnetically coupled
      to a high-spin iron(II) ion to give an S = 3/2 ground state. Reversible single
      electron reduction occurs at the ligand singly occupied molecular orbital (SOMO),
      affording a dianionic tetrazene ligand while leaving the metal oxidation state
      and spin state unchanged.

PMID- 19397282
TI  - Replication past the N5-methyl-formamidopyrimidine lesion of deoxyguanosine by
      DNA polymerases and an improved procedure for sequence analysis of in vitro
      bypass products by mass spectrometry.
AB  - Oligonucleotides containing a site-specific N(6)-(2-deoxy-d-erythro
      pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine
      (MeFapy-dGuo) lesion were synthesized, and their in vitro replication by
      Escherichia coli DNA polymerase I Klenow fragment (exo(-)) and Sulfolobus
      solfataricus P2 DNA polymerase IV (Dpo4) resulted in the misincorporation of Ade,
      Gua, and Thy opposite the MeFapy-dGuo lesion in addition to the correct insertion
      of Cyt. However, sequencing of the full-length extension products revealed that
      the initial insertion of Cyt opposite the lesion was extended most efficiently.
      Two sequences were examined, and the misincorporation was sequence-dependent.
      Improvements in the method for the mass spectrometric sequencing of the extension
      products were developed; a 5'-biotinylated primer strand was used that contained
      a dUrd near the template-primer junction. The extended primer was immobilized
      with streptavidin-coated beads, allowing it to be washed free of polymerase, the
      template strand, and other reagents. The extended primer was cleaved from the
      solid support with uridine DNA deglycosylase and piperidine treatment, and the
      extension products were sequenced by LC-ESI-MS-MS. The purification steps
      afforded by the biotinylated primer resulted in improved sensitivity for the MS
      analysis. Translesion synthesis of a template with a local 5'-T-(MeFapy-dGuo)-G
      3' sequence resulted in only error-free bypass and extension, whereas a template
      with a local 5'-T-(MeFapy-dGuo)-T-3' sequence also resulted in an interesting
      deletion product and the misincorporation of Ade opposite the MeFapy-dGuo lesion.

PMID- 19397285
TI  - Experimental evidence for the participation of 5d Gd(III) orbitals in the
      magnetic interaction in Ni-Gd complexes.
AB  - The syntheses, structural determinations, and magnetic studies of two trinuclear
      Ni-Gd-Ni complexes are described. The structural studies demonstrate that the two
      complexes present a linear arrangement of the Ni and Gd ions, with Ni ions in
      slightly distorted square-pyramidal or octahedral environments in complexes 1 and
      2, respectively. The Ni and Gd ions are linked by two or three phenoxo bridges,
      so that complexes 1 and 2 present edge-sharing or face-sharing bridging cores.
      Ferromagnetic interactions operate in these complexes. While a unique J parameter
      is able to fit the magnetic data of complex 2, two very different J constants are
      needed for 1. This result is at first sight surprising, for the structural data
      of the two Ni-O(2)-Gd cores in complex 1 are quite similar (similar Ni-O and Gd-O
      bond lengths, similar angles, and dihedral angles), the only difference coming
      from the angle between the planes defined by the Gd ion and the two bridging
      phenoxo oxygen atoms of each Ni-O(2)-Gd half core. This latter magnetic behavior
      can be considered as a signature for the participation of 5d Gd(III) orbitals in
      the exchange interaction mechanism and can explain why edge-sharing complexes
      have larger J parameters than face-sharing complexes.

PMID- 19397281
TI  - Chemistry and biology of DNA containing 1,N(2)-deoxyguanosine adducts of the
      alpha,beta-unsaturated aldehydes acrolein, crotonaldehyde, and 4-hydroxynonenal.
AB  - The alpha,beta-unsaturated aldehydes (enals) acrolein, crotonaldehyde, and trans
      4-hydroxynonenal (4-HNE) are products of endogenous lipid peroxidation, arising
      as a consequence of oxidative stress. The addition of enals to dG involves
      Michael addition of the N(2)-amine to give N(2)-(3-oxopropyl)-dG adducts,
      followed by reversible cyclization of N1 with the aldehyde, yielding 1,N(2)-dG
      exocyclic products. The 1,N(2)-dG exocyclic adducts from acrolein,
      crotonaldehyde, and 4-HNE exist in human and rodent DNA. The enal-induced 1,N(2)
      dG lesions are repaired by the nucleotide excision repair pathway in both
      Escherichia coli and mammalian cells. Oligodeoxynucleotides containing
      structurally defined 1,N(2)-dG adducts of acrolein, crotonaldehyde, and 4-HNE
      were synthesized via a postsynthetic modification strategy. Site-specific
      mutagenesis of enal adducts has been carried out in E. coli and various mammalian
      cells. In all cases, the predominant mutations observed are G-->T transversions,
      but these adducts are not strongly miscoding. When placed into duplex DNA
      opposite dC, the 1,N(2)-dG exocyclic lesions undergo ring opening to the
      corresponding N(2)-(3-oxopropyl)-dG derivatives. Significantly, this places a
      reactive aldehyde in the minor groove of DNA, and the adducted base possesses a
      modestly perturbed Watson-Crick face. Replication bypass studies in vitro
      indicate that DNA synthesis past the ring-opened lesions can be catalyzed by pol
      eta, pol iota, and pol kappa. It also can be accomplished by a combination of
      Rev1 and pol zeta acting sequentially. However, efficient nucleotide insertion
      opposite the 1,N(2)-dG ring-closed adducts can be carried out only by pol iota
      and Rev1, two DNA polymerases that do not rely on the Watson-Crick pairing to
      recognize the template base. The N(2)-(3-oxopropyl)-dG adducts can undergo
      further chemistry, forming interstrand DNA cross-links in the 5'-CpG-3' sequence,
      intrastrand DNA cross-links, or DNA-protein conjugates. NMR and mass
      spectrometric analyses indicate that the DNA interstand cross-links contain a
      mixture of carbinolamine and Schiff base, with the carbinolamine forms of the
      linkages predominating in duplex DNA. The reduced derivatives of the enal
      mediated N(2)-dG:N(2)-dG interstrand cross-links can be processed in mammalian
      cells by a mechanism not requiring homologous recombination. Mutations are rarely
      generated during processing of these cross-links. In contrast, the reduced
      acrolein-mediated N(2)-dG peptide conjugates can be more mutagenic than the
      corresponding monoadduct. DNA polymerases of the DinB family, pol IV in E. coli
      and pol kappa in human, are implicated in error-free bypass of model acrolein
      mediated N(2)-dG secondary adducts, the interstrand cross-links, and the peptide
      conjugates.

PMID- 19397286
TI  - Volatility, high thermal stability, and low melting points in heavier alkaline
      earth metal complexes containing tris(pyrazolyl)borate ligands.
AB  - Treatment of MI(2) (M = Ca, Sr) or BaI(2)(THF)(3) with 2 equiv of potassium
      tris(3,5-diethylpyrazolyl)borate (KTp(Et2)) or potassium tris(3,5-di-n
      propylpyrazolyl)borate (KTp(nPr2)) in hexane at ambient temperature afforded
      CaTp(Et2)(2) (64%), SrTp(Et2)(2) (64%), BaTp(Et2)(2) (67%), CaTp(nPr2)(2) (51%),
      SrTp(nPr2)(2) (75%), and BaTp(nPr2)(2) (39%). Crystal structure determinations of
      CaTp(Et2)(2), SrTp(Et2)(2), and BaTp(Et2)(2) revealed monomeric structures. X-ray
      structural determinations for strontium tris(pyrazolyl)borate (SrTp(2)) and
      barium tris(pyrazolyl)borate ([BaTp(2)](2)) show that SrTp(2) exists as a monomer
      and [BaTp(2)](2) exists as a dimer containing two bridging Tp ligands. The
      thermogravimetric analysis traces, preparative sublimations, and melting
      point/decomposition determinations demonstrate generally very high thermal
      stabilities and reasonable volatilities. SrTp(2) has the highest volatility with
      a sublimation temperature of 200 degrees C/0.05 Torr. [BaTp(2)](2) is the least
      thermally stable with a decomposition temperature of 330 degrees C and a percent
      residue of 46.5% at 450 degrees C in the thermogravimetric analysis trace.
      SrTp(Et2)(2), BaTp(Et2)(2), CaTp(nPr2)(2), SrTp(nPr2)(2), and BaTp(nPr2)(2)
      vaporize as liquids between 210 and 240 degrees C at 0.05 Torr. BaTp(Et2)(2) and
      BaTp(nPr2)(2) decompose at about 375 degrees C, whereas MTp(Et2)(2) and
      MTp(nPr2)(2) (M = Ca, Sr) are stable to >400 degrees C. Several of these new
      complexes represent promising precursors for chemical vapor deposition and atomic
      layer deposition film growth techniques.

PMID- 19397288
TI  - Evaluation of the antioxidant capacity, phenolic compounds, and vitamin C content
      of different peach and nectarine [ Prunus persica (L.) Batsch] breeding
      progenies.
AB  - Antioxidant capacity and contents of total phenolics, anthocyanins, flavonoids,
      and vitamin C were evaluated in 218 genotypes from 15 peach and nectarine
      breeding progenies. Significant differences were found among progenies on the
      fruit antioxidant profile, corroborated by the high contribution showed by cross
      to the phenotypic variance of each phytochemical trait analyzed (16-45%).
      Phytochemical profile varied depending on peach/nectarine and yellow/white flesh
      color qualitative traits. On the other hand, no significant effect of year was
      found on the bioactive profile of peaches and nectarines. Antioxidant capacity
      was linearly correlated to total phenolic content, but correlation varied
      depending on the progeny. No correlation was found for vitamin C versus any other
      phytochemical trait. The results suggest the importance of genetic background on
      the antioxidant profile of peaches and nectarines and stress its relevance for
      the ultimate objective of this work: selecting new peach and nectarine genotypes
      rich in bioactive compounds to benefit consumer's health.

PMID- 19397289
TI  - Core-cross-linked alginate microcapsules for cell encapsulation.
AB  - Self-cross-linkable polyelectrolyte pairs comprised of poly(methacrylic acid,
      sodium salt-co-2-[methacryloyloxy]ethyl acetoacetate) (70:30 mol ratio, A70) and
      poly-L-lysine are incorporated into CaAlg beads to form either a covalently cross
      linked shell or a core-cross-linked bead. In both cases the reactive polyanion is
      added to a solution of sodium alginate that may contain live cells and dropped
      into a calcium chloride gelling bath. Subsequent exposure to poly-L-lysine (15-30
      kDa) leads to formation of a cross-linked shell, while exposure to lower
      molecular weight poly-L-lysine (4-15 kDa) leads to formation of an
      interpenetrating matrix of covalently cross-linked synthetic polymer within the
      CaAlg template. The resulting spherical composites are resistant to chemical and
      mechanical stress yet remain cyto-compatible. This approach to cell-encapsulation
      may be useful for cell immuno-isolation in therapeutic cell transplants.

PMID- 19397290
TI  - Synthesis and self-assembly of RGD-functionalized PEO-PB amphiphiles.
AB  - Amphiphilic block copolymer self-assembly provides a versatile means to prepare
      nanoscale micelles in solution. The utilization of these structures as targeted
      drug delivery vehicles has motivated efforts to prepare bioactive ligand
      functionalized polymer micelles. The impact of ligand conjugation on micelle
      morphology was examined through use of well-characterized poly(ethylene oxide)-b
      poly(butadiene) (OB) block copolymers functionalized to varying extents with a
      biologically relevant RGD-containing peptide sequence. Micelle morphology and
      dilute solution behavior of RGD-functionalized OB (RGD-OB) copolymers were
      examined using cryogenic transmission electron microscopy (cryo-TEM) and dynamic
      mechanical analysis. The direct dispersion of RGD-OB copolymers into deionized
      water yielded a variety of structures; the observed morphologies deviated from
      the canonical series predicted by the overall change in amphiphile composition
      due to peptide conjugation. RGD functionalized spherical micelles, cylindrical
      micelle networks, and annular multilayer vesicles were prepared. The
      morphological behavior was attributed to interactions between peptide moieties
      conjugated to the termini of coronal chains and has implications in the design of
      targeting micelles for drug delivery applications.

PMID- 19397291
TI  - Enrichment mechanism of semiconducting single-walled carbon nanotubes by
      surfactant amines.
AB  - Utilization of single-walled carbon nanotubes (SWNTs) in high-end applications
      hinges on separating metallic (met-) from semiconducting (sem-) SWNTs. Surfactant
      amines, like octadecylamine (ODA) have proven instrumental for the selective
      extraction of sem-SWNTs from tetrahydrofuran (THF) nanotube suspensions. The
      chemical shift differences along the tail of an asymmetric, diacetylenic
      surfactant amine were used to probe the molecular dynamics in the presence and
      absence of nanotubes via NMR. The results suggest that the surfactant amine head
      is firmly immobilized onto the nanotube surface together with acidic water, while
      the aliphatic tail progressively gains larger mobility as it gets farther from
      the SWNT. X-ray and high-resolution TEM studies indicate that the sem-enriched
      sample is populated mainly by small nanotube bundles containing ca. three SWNTs.
      Molecular simulations in conjunction with previously determined HNO(3)/H(2)SO(4)
      oxidation depths for met- and sem-SWNTs indicate that the strong pinning of the
      amine surfactants on the sem-enriched SWNTs bundles is a result of a well-ordered
      arrangement of nitrate/amine salts separated with a monomolecular layer of H(2)O.
      Such continuous 2D arrangement of nitrate/amine salts shields the local
      environment adjacent to sem-enriched SWNTs bundles and maintains an acidic pH
      that preserves nanotube oxidation (i.e., SWNT(n+)). This, in turn, results in
      strong interactions with charge-balancing NO(3)(-) counterions that through their
      association with neutralized surfactant amines provide effective THF dispersion
      and consequent sem enrichment.

PMID- 19397292
TI  - Total synthesis of siphonazoles by the use of a conjunctive oxazole building
      block.
AB  - The preparation of 4-carbethoxy-5-methyl-2-(phenylsulfonyl)methyloxazole and its
      use in the elaboration of more complex oxazoles are described. A total synthesis
      of the unique natural products, siphonazoles A and B, illustrates an application
      of the new building block.

PMID- 19397293
TI  - Functionalized few-walled carbon nanotubes for mechanical reinforcement of
      polymeric composites.
AB  - Compared to single-walled carbon nanotubes (SWNTs) and more defective multiwalled
      carbon nanotubes (MWNTs), the thin few-walled carbon nanotubes (FWNTs) are
      believed to have extraordinary mechanical properties. However, the enhancement of
      mechanical properties in FWNTs-polymer composites has remained elusive. In this
      study, free-standing carbon nanotubes (CNTs)/polymer composite films were
      fabricated with three types (SWNTs, FWNTs, MWNTs) of functionalized CNTs. The
      mechanical properties of composite films have been investigated. It is observed
      that the Young's modulus of composite films with only 0.2 wt % functionalized
      FWNTs shows a remarkable reinforcement value of dY/dV(f) = 1658 GPa, which is
      approximately 400 GPa higher than the highest value (dY/dV(f) = 1244 GPa) that
      was previously reported. In addition, the Young's modulus increased steadily with
      the increased concentration of FWNTs. The results indicated that FWNTs are
      practically the optimum reinforcing filler for the next generation of carbon
      nanotube-based composite materials.

PMID- 19397294
TI  - Alternating current driven electroluminescence from ZnSe/ZnS:Mn/ZnS nanocrystals.
AB  - We present a novel technique for room temperature, solution-based fabrication of
      alternating current thin-film electroluminescent (AC-TFEL) devices using phosphor
      doped nanocrystals. Synthesis for stable ZnSe/ZnS:Mn/ZnS nanocrystals that
      exhibit a quantum yield of 65 +/- 5% is outlined, and their electroluminescence
      is demonstrated in structures consisting of only wide band gap ceramic layers.
      Both the nanocrystal and the ceramic films have minimal absorption across the
      visible light spectrum, enabling us to demonstrate transparent AC-TFEL devices.

PMID- 19397295
TI  - Phenyl bridging in ring-substituted cumyloxyl radicals. A product and time
      resolved kinetic study.
AB  - The reactivity of cumyloxyl radicals bearing cyclopropyl and 2,2
      diphenylcyclopropyl groups in the para position has been investigated. Depending
      on radical structure, products deriving from C-C beta-scission and/or cyclopropyl
      ring-opening are observed, supporting the hypothesis that cumyloxyl (and, more
      generally, arylcarbinyloxyl) radicals exist in equilibrium with 1
      oxaspiro[2,5]octadienyl radicals, in full agreement with the previously proposed
      mechanism for the O-neophyl rearrangement of 1,1-diarylalkoxyl radicals.

PMID- 19397296
TI  - Visible light-driven hydrogen production from aqueous protons catalyzed by
      molecular cobaloxime catalysts.
AB  - A series of cobaloxime complexes([Co(dmgH)(2)pyCl] (1), [Co(dmgH)(2)(4-COOMe
      py)Cl] (2), [Co(dmgH)(2)(4-Me(2)N-py)Cl] (3), [Co(dmgH)(dmgH(2))Cl(2)] (4),
      [Co(dmgH)(2)(py)(2)](PF(6)) (5), [Co(dmgH)(2)(P(n-Bu)(3))Cl] (6), and
      [Co(dmgBF(2))(2)(OH(2))(2)] (7), where dmgH = dimethylglyoximate monoanion,
      dmgH(2) = dimethylglyoxime, dmgBF(2) = (difluoroboryl)dimethylglyoximate anion,
      and py = pyridinewere synthesized and studied as molecular catalysts for the
      photogeneration of hydrogen from systems containing a Pt terpyridyl acetylide
      chromophore and triethanolamine (TEOA) as a sacrificial donor in aqueous
      acetonitrile. All cobaloxime complexes 1-7 are able to quench the luminescence of
      the Pt(II) chromophore [Pt(ttpy)(CCPh)]ClO(4) (C1) (ttpy = 4'-p-tolyterpyridine).
      The most effective electron acceptor for hydrogen evolution is found to be
      complex 2, which provides the fastest luminescence quenching rate constant for C1
      of 1.7 x 10(9) M(-1) s(-1). The rate of hydrogen evolution depends on many
      factors, including the stability of the catalysts, the driving force for proton
      reduction, the relative and absolute concentrations of system components (TEOA,
      Co molecular catalyst, and sensitizer), and the ratio of MeCN/water in the
      reaction medium. For example, when the concentration of TEOA increases, the rate
      of H(2) photogeneration is faster and the induction period is shorter. Colloidal
      cobalt experiments and mercury tests were run to verify that the system is
      homogeneous and that catalysis does not occur from in situ generated colloidal
      particles during photolysis. The most effective system examined to date consists
      of the chromophore C1 (1.1 x 10(-5) M), TEOA (0.27 M), and catalyst complex 1
      (2.0 x 10(-4) M) in a MeCN/water mixture (24:1 v/v, total 25 mL); this system has
      produced approximately 2150 turnovers of H(2) after only 10 h of photolysis with
      lambda > 410 nm.

PMID- 19397297
TI  - Surface diffusion and substrate-nanowire adatom exchange in InAs nanowire growth.
AB  - We report new fundamental insights into InAs nanowire (NW) nucleation and
      evolution on InAs (111)B surfaces using organometallic vapor phase epitaxy and
      present the first experimental demonstration of two distinct NW growth regimes,
      defined by the direction of substrate-NW adatom exchange, that lead to nonlinear
      growth rates. We show that the NW elongation rate and morphology in these two
      growth regimes are governed by the relative difference between the In adatom
      diffusion lengths on the growth substrate surface and on the NW sidewalls,
      resulting in strong growth rate dependence on the NW length. These results
      indicate that surface solid-phase diffusion of In adatoms is a key process in
      InAs NW growth, which is also supported by diameter-dependent growth rates. These
      developments enable rational growth of axial and radial NW heterostructures.

PMID- 19397298
TI  - Ionic field effect transistors with sub-10 nm multiple nanopores.
AB  - We report a new method to fabricate electrode-embedded multiple nanopore
      structures with sub-10 nm diameter, which is designed for electrofluidic
      applications such as ionic field effect transistors. Our method involves
      patterning pore structures on membranes using e-beam lithography and shrinking
      the pore diameter by a self-limiting atomic layer deposition process. We
      demonstrate that 70-80 nm diameter pores can be shrunk down to sub-10 nm diameter
      and that the ionic transport of KCl electrolyte can be efficiently manipulated by
      the embedded electrode within the membrane.

PMID- 19397299
TI  - A multifunctional tripodal fluorescent probe: "off-on" detection of sodium as
      well as two-input AND molecular logic behavior.
AB  - A simple tripodal sensor (3) with multifunctional capability has been synthesized
      in three steps. The sensor, a naphthalene-functionalized Schiff base, displays
      selectivity for sodium over other important physiological and environmentally
      important cations through changes in the emission spectra at lambda(max) 355 nm
      when excited at 270 nm. Interestingly, the combined addition of both sodium and
      potassium produced a new band at lambda(max) 445 nm, while the addition of sodium
      or potassium alone produced negligible changes at this wavelength. Therefore, the
      conditions of a two-input AND logic operator were also satisfied.

PMID- 19397300
TI  - Anti-selective epoxidation of methyl alpha-methylene-beta-tert
      butyldimethylsilyloxycarboxylate esters. Evidence for stereospecific oxygen atom
      transfer in a nucleophilic epoxidation process.
AB  - Methyl alpha-methylene-beta-tert-butyldimethylsilyloxycarboxylate esters are
      found to undergo diastereoselective epoxidation in the presence of potassium tert
      butoxide-tert-butyl hydroperoxide to form anti products. In an effort to better
      understand mechanistic details of the transformation and the basis of
      diastereoselectivities observed, we studied the epoxidation of substrates with
      alpha-methylene groups containing (trans) deuterium labels and discovered that
      oxygen-atom transfer proceeds with > or = 95% stereospecificity in all cases
      examined. These and other experiments suggest that the mechanism of epoxidation
      is not distinguishable from a concerted process.

PMID- 19397301
TI  - Synthesis of macrocyclic beta-strand templates by ring closing metathesis.
AB  - We report the synthesis of macrocycles 1-6 via ring closing metathesis of dienes
      7-12. Addition of chlorodicyclohexylborane to thermal and microwave assisted RCM
      of dienes 8 and 9 markedly improves the yield. The geometric isomers of
      macrocycles 1-3 and 5 have been assigned using X-ray crystallography and NMR.

PMID- 19397302
TI  - Synthesis of highly functionalized bis(4H-chromene) and 4H-benzo[g]chromene
      derivatives via an isocyanide-based pseudo-five-component reaction.
AB  - The reactive intermediates generated by the addition of alkyl, aryl, and
      alicyclic isocyanides to dialkyl acetylenedicarboxylates were trapped by 2,5
      dihydroxycyclohexa-2,5-diene-1,4-dione or 2-hydroxynaphthalene-1,4-dione to
      produce highly functionalized bis(4H-chromene)- and 4H-benzo[g]chromene-3,4
      dicarboxylate derivatives in fairly good yields in CH(3)CN at room temperature.
      These compounds are closely related to the ring systems pentalongin,
      dehydroherbarin, 1,3-disubstituted-3,4-dehydropyranonaphthoquinones, and 3
      arylpyranonaphthoquinones, which have a broad spectrum of biological activity.

PMID- 19397303
TI  - Enantioselective synthesis of (R)-tolterodine via CuH-catalyzed asymmetric
      conjugate reduction.
AB  - An efficient and highly enantioselective method for the preparation of (R)
      tolterodine is described. The synthesis was performed by CuH-catalyzed asymmetric
      conjugate reduction of a beta,beta-diaryl-substituted unsaturated nitrile as a
      key step, which is prepared by a stereoselective hydroarylation of alkynenitrile
      with aryl boronic acid. The synthesis was accomplished without employing the
      protection-deprotection sequence.

PMID- 19397304
TI  - Peptide storage: are you getting the best return on your investment? Defining
      optimal storage conditions for proteomics samples.
AB  - To comply with current proteomics guidelines, it is often necessary to analyze
      the same peptide samples several times. Between analyses, the sample must be
      stored in such a way as to conserve its intrinsic properties, without losing
      either peptides or signal intensity. This article describes two studies designed
      to define the optimal storage conditions for peptide samples between analyses.
      With the use of a label-free strategy, peptide conservation was compared over a
      28-day period in three different recipients: standard plastic tubes, glass tubes,
      and low-adsorption plastic tubes. The results of this study showed that standard
      plastic tubes are unsuitable for peptide storage over the period studied. Glass
      tubes were found to perform better than standard plastic, but optimal peptide
      recovery was achieved using low-adsorption plastic tubes. The peptides showing
      poor recovery following storage were mainly hydrophobic in nature. The
      differences in peptide recovery between glass and low-adsorption plastic tubes
      were further studied using isotopically labeled proteins. This study allowed
      accurate comparison of peptide recovery between the two tube types within the
      same LC-MS run. The results of the label-free study were confirmed. Further, it
      was possible to demonstrate that peptide recovery in low-adsorption plastic tubes
      was optimal whatever the peptide concentration stored.

PMID- 19397305
TI  - A computational comparison of electron transfer from reduced ferredoxin to flavin
      adenine dinucleotide and a gold electrode.
AB  - We have carried out calculations of the electronic structure of ferredoxin and of
      the electronic coupling matrix element Hif for electron transfer from reduced
      ferredoxin to flavin adenine dinucleotide (FAD) and to cluster models of the
      Au111 surface and a Au111 surface with a mercaptopyridene self-assembled
      monolayer (SAM). We conclude, based on Hif2, that a gold electrode is
      approximately 14 times less efficient as an electron acceptor than FAD and that
      the mercaptopyridine SAM enhances electron transfer. The magnitude of Hif is
      large enough for these systems that the weak coupling limit approximations may no
      longer be valid. However, the barrier to electron transfer in the strong coupling
      limit is computed to be small due to minimal geometry change between oxidized and
      reduced ferredoxin. MD simulations of the interaction of ferredoxin and
      protonated pyridine within a water solvation box indicate that the protonated
      pyridine does strongly orient the ferredoxin, favoring electron transfer as
      compared to a bare gold surface, where we speculate the orientation of the
      ferredoxin may be more random.

PMID- 19397306
TI  - Facile solubilization of organochalcogen compounds in mixed micelle formation of
      binary and ternary cationic-nonionic surfactant mixtures.
AB  - This study investigated the water solubility enhancements of organochalcogen
      compounds, viz. bis(diphenylmethyl)diselenide [(C6H5)2CHSe]2 and 3,3'-dibromo
      4,4'-dimethyl-2-dipyridyl diselenide [C12H10N2Se2Br2] in micellar media. Two
      cationic and one nonionic surfactants possessing the same hydrocarbon tail,
      namely hexadecyltrimethylammonium bromide (C16Br), hexadecyltrimethylammonium
      chloride (C16Cl), and polyoxyethylene(20)mono-n-hexadecyl ether (Brij 58), in
      their single as well as equimolar binary and ternary mixed states have been used.
      Solubilization capacity has been evaluated in terms of the molar solubilization
      ratio and the micelle water partition coefficients. The association constants
      between the solubilizate molecules and that of micelle and the average number of
      solubilizate molecules per micelle have also been quantified. The results showed
      that cationic surfactants exhibit less solubilization as compared to nonionic
      surfactant. The mixing effects of surfactants on micelle formation and
      solubilization efficiencies have also been discussed. It has been observed that
      cationic-nonionic binary combinations showed better solubilization capacity as
      compared to pure cationic, nonionic, or cationic-cationic binary mixtures. An
      equimolar cationic-cationic-nonionic ternary surfactant system provides higher
      solubilization than cationic-cationic but lowers than their cationic-nonionic
      counterpart. In addition, Fourier transform infrared has been employed with fair
      success to predict the information regarding the aggregates and the mechanism of
      docking of the surfactant and the chalcogenides in the system. The analysis has
      provided valuable information for the selection of mixed surfactants for
      solubilizing water-insoluble compounds. Certainly the solubilization ability of
      these surfactants is not simply related to molar capacity. The results give
      sufficient encouragement to warrant more detailed investigation of the features
      of surfactant properties that affect solubilization.

PMID- 19397307
TI  - Fluorinated boroxin-based anion receptors for lithium ion batteries: fluoride
      anion binding, ab initio calculations, and ionic conductivity studies.
AB  - Novel fluorinated boroxines, tris(2,6-difluorophenyl)boroxin (DF), tris(2,4,6
      trifluorophenyl)boroxin (TF), and tris(pentafluorophenyl)boroxin (PF), have been
      investigated for potential applications in lithium ion batteries through fluoride
      anion binding, ab initio calculations, and ionic conductivity measurements.
      Structures of the fluorinated boroxines and boroxin-fluoride complexes have been
      confirmed by comparing their (19)F and (11)B NMR chemical shifts with those
      obtained by the DFT-GIAO method. The stoichiometry of the fluoride anion binding
      to these boroxines has been shown to be 1:1 using (19)F NMR and UV-vis
      spectroscopy. UV-vis spectroscopic studies show the coexistence of more than one
      complex, in addition to the 1:1 complex, for perfluorinated boroxin, PF. DFT
      calculations (B3LYP/6-311G**) show that the fluoride ion complex of DF prefers
      unsymmetrical, covalently bound structure (7) over the symmetrically bridged
      species (10) by 12.5 kcal/mol. Rapid equilibration of the fluoride anion among
      the three borons in these boroxines results in a single (19)F NMR absorption for
      all of the aromatic ortho- or para-fluorines at ambient temperature. The effect
      of these anion receptors on lithium ion conductivities was also explored for
      potential applications in dual ion intercalating lithium batteries.

PMID- 19397308
TI  - Formation and efflux of ATP-binding cassette transporter substrate 2,4
      dinitrophenyl-S-glutathione from cultured human term placental villous tissue
      fragments.
AB  - Upon exposure to 1-chloro-2,4-dinitrobenzene (CDNB), the human placental tissue
      forms its glutathione conjugate 2,4-dinitrophenyl-S-glutathione (DNP-SG). The
      purpose of this study was to investigate the involvement of human placental ATP
      binding cassette (ABC) transporters in the efflux of DNP-SG. Placental tissue
      samples were obtained from pregnant patients undergoing C-section deliveries
      following normal pregnancies; villous tissue was cultured in suspension, and DNP
      SG formation and efflux upon exposure to 100 microM CDNB were measured by HPLC.
      DNP-SG efflux decreased by 69.1 (+/-11.3)%, 51.1 (+/-5.4)%, 56.7 (+/-8.3)% and
      53.6 (+/-10.8)% (p < 0.05) in the presence of 5 mM sodium orthovanadate (ATPase
      inhibitor), 100 microM MK571 (MRP-inhibitor), 1 mM dipyridamole (BCRP/P-gp/MRP1
      inhibitor) and 100 microM verapamil (P-gp/MRP1 inhibitor) respectively, without
      any change in DNP-SG formation, total tissue glutathione, GSH/GSSG ratio, tissue
      integrity or tissue viability. These data clearly established the role of ABC
      transporters in the human placental efflux of DNP-SG. To investigate the
      contribution of various ABC transporters toward DNP-SG transport, ATP-dependent
      transport of 3H-DNP-SG was determined in Sf9 membrane vesicles overexpressing P
      gp, BCRP and the MRP proteins. MRP1-mediated DNP-SG transport was inhibited in
      the presence of sodium orthovanadate, MK571, dipyridamole and verapamil in the
      presence of glutathione. Furthermore, MRP1-mediated transport [K(t) = 11.3 +/-
      1.3 microM and v(max) = 86.7 +/- 1.9 pmol/mg/min] was a high-affinity process
      compared to MRP2-mediated transport [K(t) = 168 +/- 7 microM and v(max) = 1367 +/
      18 pmol/mg/min]. The inhibition pattern and the kinetics of DNP-SG efflux in the
      placental villous tissue were consistent with MRP1-mediated DNP-SG efflux,
      suggesting a functional role and an apical localization for an MRP1-like
      transporter in the human placental syncytiotrophoblast.

PMID- 19397309
TI  - Theoretical investigation of the reaction of CF(3)CHFOCH(3) with OH radical.
AB  - A direct ab initio dynamics method was used to study the mechanism and kinetics
      of the reaction CF(3)CHFOCH(3) + OH. Two reaction channels, R1 and R2, were
      found, corresponding to H-abstraction from a CH(3) group and a CHF group,
      respectively. The potential energy surface (PES) information was obtained at the
      G3(MP2)//MP2/6-311G(d,p) level. The standard enthalpies of formation for the
      reactant (CF(3)CHFOCH(3)) and products (CF(3)CHFOCH(2) and CF(3)CFOCH(3)) were
      evaluated via isodesmic reactions at the same level. Furthermore, the rate
      constants of two channels were calculated using the canonical variational
      transition state theory (CVT) with small-curvature tunneling (SCT) contributions
      over a wide temperature range of 200-3000 K. The dynamic calculations demonstrate
      that reaction R1 dominates the overall reaction when the temperature is lower
      than 800 K whereas reaction R2 becomes more competitive in the higher temperature
      range. The calculated rate constants and branching ratios are both in good
      agreement with the available experimental values.

PMID- 19397310
TI  - FIONA on Caenorhabditis elegans.
AB  - Despite much work, subcellular neurons of Caenorhabditis elegans have not been
      studied at nanometer resolution with millisecond time resolution. Nor has there
      been an effective way to immobilize C. elegans. Here we show that, without using
      anesthetic or paralyzing agents, fluorescence imaging with one-nanometer accuracy
      (FIONA) can be successfully applied to fluorescently labeled molecules within C.
      elegans nerves. GFP- and DENDRA2-labeled ELKS punctae can be localized with sub
      10 nm accuracy in approximately 5 ms. Our results show that the protein ELKS is
      occasionally transferred by microtubule-based motors. This is the first example
      of FIONA applied to a living organism.

PMID- 19397313
TI  - Bis-enaminone based parallel solution-phase synthesis of 1,4-dihydropyridine
      derivatives.
AB  - Two variations of a parallel solution-phase synthesis of N-substituted dimethyl 4
      oxo-1,4-dihydropyridine-3,5-dicarboxylates 4 and methyl 3-oxo-3,5-dihydro-2H
      pyrazolo[4,3-c]pyridine-7-carboxylates 9 from dimethyl acetone-1,3-dicarboxylate
      (1) were developed. The first synthetic method comprises preparation of the bis
      enaminone reagents 2 and 8 and their cyclization with primary amines 3 via double
      substitution of both dimethylamino groups to give dihydropyridines (DHPs) 4 and
      9, respectively. Another variation consists of preparation of the monoenaminone
      reagents 5 and 10, followed by substitution of the dimethylamino group with
      primary amines 3, and cyclization of the so formed intermediates 6 with N,N
      dimethylformamide dimethylacetal (DMFDMA). In this manner, a library of 46
      analytically pure compounds, 24 intermediates 6, 11, and 13, and 22 final
      dihydropyridines 4 and 9 was obtained employing just a simple filtration workup.

PMID- 19397311
TI  - Crystal structures of cytochrome P450 2B4 in complex with the inhibitor 1
      biphenyl-4-methyl-1H-imidazole: ligand-induced structural response through alpha
      helical repositioning.
AB  - Two different ligand occupancy structures of cytochrome P450 2B4 (CYP2B4) in
      complex with 1-biphenyl-4-methyl-1H-imidazole (1-PBI) have been determined by X
      ray crystallography. 1-PBI belongs to a series of tight binding, imidazole-based
      CYP2B4 inhibitors. 1-PBI binding to CYP2B4 yields a type II spectrum with a K(s)
      value of 0.23 microM and inhibits enzyme activity with an IC(50) value of 0.035
      microM. Previous CYP2B4 structures have shown a large degree of structural
      movement in response to ligand size. With two phenyl rings, 1-PBI is larger than
      1-(4-chlorophenyl)imidazole (1-CPI) and 4-(4-chlorophenyl)imidazole (4-CPI) but
      smaller than bifonazole, which is branched and contains three phenyl rings. The
      CYP2B4-1-PBI complex is a structural intermediate to the closed CPI and the open
      bifonazole structures. The B/C-loop reorganizes itself to include two short
      partial helices while closing one side of the active site. The F-G-helix cassette
      pivots over the I-helix in direct response to the size of the ligand in the
      active site. A cluster of Phe residues at the fulcrum of this pivot point allows
      for dramatic repositioning of the cassette with only a relatively small amount of
      secondary structure rearrangement. Comparisons of ligand-bound CYP2B4 structures
      reveal trends in plastic region mobility that could allow for predictions of
      their position in future structures based on ligand shape and size.

PMID- 19397314
TI  - Investigation of novel bis- and tris-tetraazamacrocycles for use in the copper-64
      ((64)Cu) radiolabeling of antibodies with potential to increase the therapeutic
      index for drug targeting.
AB  - The (64)Cu complexes of a series of mono-, bis-, and tris-tetraazamacrocycles
      have been prepared, and their stability in human sera has been assessed. The
      ligands forming the most stable Cu(2+) complexes were then conjugated to the
      B72.3 antibody (mAb). Conditions for conjugation of the ligands to the mAb were
      optimized for the concentration of protein, ligand, pH, temperature, and time.
      The optimum moles of Cu(2+) attached to the mAb were as high as 3.5 for L2 and
      5.5 or 2.7 for L5, and the immunoreactivity was > or =80%. Biodistribution of the
      radioimmunoconjugates showed good tumor localization and target-to-background
      ratios that were significantly enhanced compared to those achieved with
      monotetraazamacrocyclic derivatives.

PMID- 19397315
TI  - Critical properties and high-pressure volumetric behavior of the carbon
      dioxide+propane system at T=308.15 k. Krichevskii function and related
      thermodynamic properties.
AB  - Critical properties and volumetric behavior for the {CO2(1)+C3H8(2)} system have
      been studied. The critical locus was measured with a flow apparatus and detected
      by critical opalescence. For the mixtures, repeatabilities in critical
      temperature and pressure are rTc<or=0.15 K and rPc<or=0.013 MPa, respectively,
      and the confidence intervals calculated are c.i.(Tc)<0.32 K and c.i.(Pc)<0.034
      MPa. The value for the Krichevskii parameter, AKr=-4.12 MPa, was obtained from
      the experimental critical data in this work. Additionally, the density
      measurements of 15 {CO2(1)+C3H8(2)} binary mixtures at 308.15 K and pressures up
      to 20 MPa were carried out using an Anton Paar DMA 512-P vibrating-tube
      densimeter calibrated with the forced path mechanical calibration model. The mean
      relative standard deviation of density, srhor, was estimated to be better than
      0.1%, and the uncertainties in temperature and pressure are +/-0.01 K and +/
      0.001 MPa, respectively. In the experimental setup, an uncertainty in the mole
      fraction, u(xj)=+/-0.0015, has been achieved. Other properties related to P-rho-T
      x data such as saturated densities, rhoL and rhoV, compressibility factor, Z,
      excess molar volumes,VmE, and partial molar volumes, Vi, have been calculated.
      Structural properties such as direct and total correlation function integrals and
      cluster size were calculated using the Krichevskii function concept. Both the
      critical and volumetric behavior have been compared with literature data and with
      those obtained from the PC-SAFT and Patel-Teja equations of state.

PMID- 19397316
TI  - Localized generation of attoliter protein solution droplets by electrofocused
      liquid-liquid separation.
AB  - We develop a simple technique for the generation of droplets of a high
      concentration protein solution of attoliter volume and a diameter of >or=500 nm,
      containing several thousand protein molecules, and their accurate deposition on
      micron-size electrodes, standalone or in an array. The technique is based on
      liquid-liquid phase separation in the homogeneous region of the phase diagram,
      induced by a nonuniform weak electric field, which also accurately directs the
      generated droplets toward the electrode. We show that the protein molecules are
      not chemically modified and retain their integrity, conformation, and activity
      post deposition. The technique is applicable to the manufacture of various types
      of protein/microelectrode arrays and is tunable, scalable, and applicable to a
      broad range of proteins.

PMID- 19397318
TI  - Lipophilicity of basic drugs measured by hydrophilic interaction chromatography.
AB  - RPLC gains acceptance in pharmaceutical research for the rapid determination of
      lipophilicity but remains limited for the determination of partition coefficients
      of moderate to strong basic compounds under their neutral form because stationary
      phases are not compatible with high pH conditions. In this work, HILIC technique
      was used to accurately measure log P(oct) of the neutral form of basic drugs by
      measuring the difference between 2 isocratic log k values (Delta log k(0-95)) of
      their cationic form.

PMID- 19397319
TI  - Engineered apoptosis-inducing peptides with enhanced mitochondrial localization
      and potency.
AB  - Apoptosis-inducing peptides that trigger mitochondrial disruption are a popular
      tool in pharmaceutical and anticancer research. While useful, their potencies are
      low, which impedes further development of drugs based on these sequences. Here,
      we describe an effort to engineer the intracellular localization and activity of
      a peptide with known anticancer activity, D-(KLAKLAK)(2), to improve potency by
      increasing the specificity of the peptide for mitochondria and enhancing
      disruption of this organelle. The engineered peptides are significantly more
      toxic to a wide variety of cancer cell lines, with the best analogue exhibiting a
      LC(50) value 100-fold lower than the parent compound. Importantly, the peptides
      maintain their potency when made cell-type specific.

PMID- 19397320
TI  - Exploration of structure-activity relationship determinants in analogue series.
AB  - A computational methodology is introduced to systematically organize compound
      analogue series according to substitution sites and identify combinations of
      sites that determine structure-activity relationships (SARs) and make large
      contributions to SAR discontinuity. These sites are prime targets for further
      chemical modification. The approach involves the analysis of substitution
      patterns in "combinatorial analogue graphs" (CAG) and the application of an SAR
      analysis function to evaluate contributions of variable R-groups. It is
      applicable to analogue series spanning different potency ranges, for example,
      analogues taken from lead optimization programs or screening data sets (where
      potency differences might be subtle). In addition to determining key substitution
      patterns that cause significant SAR discontinuity, CAG analysis also identifies
      "SAR holes", i.e., nonexplored combinations of substitution sites, and SAR
      regions that are under-sampled in analogue series.

PMID- 19397321
TI  - Replacement of a thiourea-S with an amidine-NH donor group in a platinum-acridine
      antitumor compound reduces the metal's reactivity with cysteine sulfur.
AB  - The reactivity of two DNA-targeted platinum-acridine conjugates with cysteine
      sulfur was studied. The conjugate containing an amidine-NH donor group cis to the
      chloride leaving group showed considerably reduced reactivity with N
      acetylcysteine compared to the prototypical derivative containing a thiourea-S
      linkage. The opposite scenario has been observed previously in reactions with
      nucleobase nitrogen. Possible consequences of the unique target-selective tuning
      of the substitution chemistry for the pharmacodynamic properties and biological
      activity of these agents are discussed.

PMID- 19397322
TI  - Synthesis, activity, and pharmacophore development for isatin-beta
      thiosemicarbazones with selective activity toward multidrug-resistant cells.
AB  - We have recently identified a new class of compounds that selectively kill cells
      that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers
      multidrug resistance on cancer cells. Several isatin-beta-thiosemicarbazones from
      our initial study have been validated and a range of analogues synthesized and
      tested. A number demonstrated improved MDR1-selective activity over the lead,
      NSC73306 (1). Pharmacophores for cytotoxicity and MDR1 selectivity were generated
      to delineate the structural features required for activity. The MDR1-selective
      pharmacophore highlights the importance of aromatic/hydrophobic features at the
      N4 position of the thiosemicarbazone and the reliance on the isatin moiety as key
      bioisosteric contributors. Additionally, a quantitative structure-activity
      relationship (QSAR) model that yielded a cross-validated correlation coefficient
      of 0.85 effectively predicts the cytotoxicity of untested thiosemicarbazones.
      Together, the models serve as effective approaches for predicting structures with
      MDR1-selective activity and aid in directing the search for the mechanism of
      action of 1.

PMID- 19397324
TI  - Synthesis and biological activities of topoisomerase I inhibitors, 6
      arylmethylamino analogues of edotecarin.
AB  - The replacement of 1,3-dihydroxy-2-propylamino moiety at the N6-position of
      edotecarin (1) by arylmethylamino groups yielded a number of more potent
      topoisomerase I inhibitors with better cytotoxic (CTX) activities in vitro than
      edotecarin. Among them, the three most potent pyridylmethyl analogues, compounds
      22g, 22m, and 23c, showed better antitumor activities against MKN-45 human
      stomach cancer or MX-1 human breast cancer xenografted mice than those of
      edotecarin. Furthermore, compounds 22m and 23c exhibited complete response
      against MX-1 cells implanted in mice.

PMID- 19397323
TI  - Design, synthesis, and pharmacological effects of a cyclization-activated steroid
      prodrug for colon targeting in inflammatory bowel disease.
AB  - Glucocorticoids are used in the treatment of inflammatory bowel disease. A
      limitation to their use is that they undergo absorption from the GIT before
      reaching the colon causing severe systemic side effects. We report here on a
      novel prodrug approach to targeting corticosteroids to the colon. The design
      involves attaching a 21-ester group that suppresses absorption during transit to
      the colon. The prodrug is designed to be primed by colonic microflora liberating
      an amino ester that cyclizes releasing the steroid. One of the prodrugs 5b was as
      efficacious as prednisolone in the murine DSS model but did not cause thymic
      atrophy, a marker for systemic steroid effects.

PMID- 19397326
TI  - A chiral 60-metal sodalite cage featuring 24 vertex-sharing [Er4(mu3-OH)4]
      cubanes.
AB  - A chiral, cagelike, high-nuclearity lanthanide hydroxide cluster containing 60
      Er(III) ions is reported. The cluster core possesses a fascinating sodalite-like
      structure with 24 vertex-sharing cubane-like [Er(4)(mu(3)-OH)(4)](8+) units. The
      hexagonal face of the sodalite cage features a templating mu(6)-CO(3)(2-) ion.
      Magnetic studies revealed weak antiferromagnetic interactions.

PMID- 19397325
TI  - Construction of multifunctional cuboctahedra via coordination-driven self
      assembly.
AB  - We present a general strategy for the synthesis of stable, multifunctional
      cuboctahedral complexes in which coordination-driven self-assembly allows for
      precise control over positioning of either ferrocene or crown ether
      functionalities. The appropriate stoichiometric combination of functionalized 120
      degree diplatinum acceptor units with tritopic donor units afforded
      supramolecular cuboctahedra with covalently linked functional groups. The
      compounds are characterized by multinuclear NMR spectroscopy, electrospray
      ionization mass spectrometry, and electrochemistry.

PMID- 19397327
TI  - Frontier orbital description of the Si(100) surface: a route to symmetry-allowed
      and concerted [2 + 2] cycloadditions.
AB  - We present a conceptually simple frontier orbital description of an ideal Si(100)
      surface by extending the standard orbital description for a single Si dimer unit
      across the surface Brillouin zone. Density functional theory calculations are
      used to order the predicted frontier wave functions in terms of energy. When
      applied to the p(2 x 1) and c(4 x 2) reconstructions, this analysis provides a
      route for the controversial [2 + 2] cycloaddition reaction, which was previously
      thought to involve a violation of the Woodward-Hoffman rules. The calculated
      frontier states are shown to be a valuable aid in describing reactivity on
      Si(100) that is consistent with experiment and provides a rational means to
      predict allowed reaction products on Si(100).

PMID- 19397329
TI  - Well-defined organic nanotubes from multicomponent bottlebrush copolymers.
AB  - Bottlebrush copolymers are comblike macromolecules with densely grafted polymeric
      branches that adopt a cylindrical shape in solutions. We demonstrate a new method
      for the preparation of organic nanotubes by single molecule templating of core
      shell bottlebrush copolymers. Multicomponent bottlebrush copolymers with well
      defined structural parameters are synthesized by a combination of different
      living polymerization methods. Tubular structures can be prepared by cross
      linking the shell layer and selectively etching out the core. The shape and size
      of original bottlebrush macromolecules are preserved during these
      transformations, which leads to the formation of well-defined organic nanotubes.
      The length and diameter of nanotubes are dictated by the length of the backbones
      and branches of the polymeric precursors, respectively. Water-soluble nanotubes
      with a hydrophobic interior can be prepared from bottlebrush copolymers with
      triblock copolymer branches. Herein, we outline molecular design strategies to
      fabricate nanotubes with controlled lengths, open pores, and different solubility
      characteristics.

PMID- 19397328
TI  - Enhanced long-term stability for single ion channel recordings using suspended
      poly(lipid) bilayers.
AB  - Black lipid membranes (BLMs) are widely used for recording the activity of
      incorporated ion channel proteins. However, BLMs are inherently unstable
      structures that typically rupture within a few hours after formation. Here,
      stabilized BLMs were formed using the polymerizable lipid bis-dienoyl
      phosphatidylcholine (bis-DenPC) on glass pipettes of approximately 10 microm
      (I.D.). After polymerization, these BLMs maintained steady conductance values for
      several weeks, as compared to a few hours for unpolymerized membranes. The
      activity of an ion channel, alpha-hemolysin, incorporated into bis-DenPC BLMs
      prior to polymerization, was maintained for 1 week after BLM formation and
      polymerization. These lifetimes are a substantial improvement over those
      achievable with conventional BLM technologies. Polymerized BLMs containing
      functional ion channels may represent an enabling technology for development of
      robust biosensors and drug screening devices.

PMID- 19397331
TI  - Structure of aqueous solutions of monosodium glutamate.
AB  - We studied monosodium glutamate (MSG) in aqueous solution using molecular
      dynamics simulations and compared the results with recent neutron diffraction
      with isotope contrast variation/empirical potential structure refinement (EPSR)
      data obtained on the same system (McLain et al. J. Phys. Chem. B 2006, 110, 21251
      21258). We used classical simulations with empirical force fields to study both
      dilute and more concentrated (1.40 M) solutions. To gauge the importance of
      polarization and other quantum effects, we carried out first-principles molecular
      dynamics in the dilute case. The glutamate structure was well reproduced by the
      OPLS/AA and SPC/E force fields: we found a reasonable agreement between the
      simulations and the experimental data with respect to the hydration numbers for
      glutamate carboxylate and amine groups and the observation of significant sodium
      ion-carboxylate binding. However, none of our simulations could reproduce the
      dramatic reduction in water-water correlations observed experimentally.
      Simulations showed a large amount of carboxylate-amine binding, as well as
      segregation of water and glutamate, at moderately high concentrations of MSG. We
      attribute this result to the breakdown of currently available classical force
      fields when applied to concentrated ionic solutions, especially large polyatomic
      ions. We also did not observe the sharing of a water proton by two carboxylate
      oxygens simultaneously, and we argue against this interpretation of EPSR data on
      a variety of physical grounds. We offer several suggestions to resolve these
      discrepancies between simulation and the current interpretation of neutron
      diffraction data, which should advance the understanding of aqueous ionic
      solutions in general.

PMID- 19397330
TI  - Characterizing the role of ensemble modulation in mutation-induced changes in
      binding affinity.
AB  - Protein conformational fluctuations are key contributors to biological function,
      mediating important processes such as enzyme catalysis, molecular recognition,
      and allosteric signaling. To better understand the role of conformational
      fluctuations in substrate/ligand recognition, we analyzed, experimentally and
      computationally, the binding reaction between an SH3 domain and the recognition
      peptide of its partner protein. The fluctuations in this SH3 domain were
      enumerated by using an algorithm based on the hard sphere collision model, and
      the binding energetics resulting from these fluctuations were calculated using a
      structure-based energy function parametrized to solvent accessible surface areas.
      Surprisingly, this simple model reproduced the effects of mutations on the
      experimentally determined SH3 binding energetics, within the uncertainties of the
      measurements, indicating that conformational fluctuations in SH3, and in
      particular the RT loop region, are structurally diverse and are well-approximated
      by the randomly configured states. The mutated positions in SH3 were distant to
      the binding site and involved Ala and Gly substitutions of solvent exposed
      positions in the RT loop. To characterize these fluctuations, we applied
      principal coordinate analysis to the computed ensembles, uncovering the principal
      modes of conformational variation. It is shown that the observed differences in
      binding affinity between each mutant, and thus the apparent coupling between the
      mutated sites, can be described in terms of the changes in these principal modes.
      These results indicate that dynamic loops in proteins can populate a broad
      conformational ensemble and that a quantitative understanding of molecular
      recognition requires consideration of the entire distribution of states.

PMID- 19397332
TI  - Biological barriers to therapy with antisense and siRNA oligonucleotides.
AB  - Attaining the full therapeutic utility of antisense and siRNA oligonucleotides
      will require understanding of the biological barriers that stand between initial
      administration of these drugs and their final actions within cells. This review
      examines some of the key barriers that affect the biodistribution of
      oligonucleotides both in molecular form and when they are associated with
      nanocarriers. An understanding of the biological processes underlying these
      barriers will aid in the design of more effective delivery systems.

PMID- 19397333
TI  - Neurite outgrowth on nanofiber scaffolds with different orders, structures, and
      surface properties.
AB  - Electrospun nanofibers can be readily assembled into various types of scaffolds
      for applications in neural tissue engineering. The objective of this study is to
      examine and understand the unique patterns of neurite outgrowth from primary
      dorsal root ganglia (DRG) cultured on scaffolds of electrospun nanofibers having
      different orders, structures, and surface properties. We found that the neurites
      extended radially outward from the DRG main body without specific directionality
      when cultured on a nonwoven mat of randomly oriented nanofibers. In contrast, the
      neurites preferentially extended along the long axis of fiber when cultured on a
      parallel array of aligned nanofibers. When seeded at the border between regions
      of aligned and random nanofibers, the same DRG simultaneously expressed aligned
      and random neurite fields in response to the underlying nanofibers. When cultured
      on a double-layered scaffold where the nanofibers in each layer were aligned
      along a different direction, the neurites were found to be dependent on the fiber
      density in both layers. This biaxial pattern clearly demonstrates that neurite
      outgrowth can be influenced by nanofibers in different layers of a scaffold,
      rather than the topmost layer only. Taken together, these results will provide
      valuable information pertaining to the design of nanofiber scaffolds for
      neuroregenerative applications, as well as the effects of topology on neurite
      outgrowth, growth cone guidance, and axonal regeneration.

PMID- 19397334
TI  - Sniffing chronic renal failure in rat model by an array of random networks of
      single-walled carbon nanotubes.
AB  - In this study, we use an experimental model of bilateral nephrectomy in rats to
      identify an advanced, yet simple nanoscale-based approach to discriminate between
      exhaled breath of healthy states and of chronic renal failure (CRF) states. Gas
      chromatography/mass spectroscopy (GC-MS) in conjugation with solid-phase
      microextraction (SPME) of healthy and CRF breath, collected directly from the
      trachea of the rats, identified 15 common volatile organic compounds (VOCs) in
      all samples of healthy and CRF states and 27 VOCs that appear in CRF but not in
      healthy states. Online breath analysis via an array of chemiresistive random
      network of single-walled carbon nanotubes (SWCNTs) coated with organic materials
      showed excellent discrimination between the various breath states. Stepwise
      discriminate analysis showed that enhanced discrimination capacity could be
      achieved by decreasing the humidity prior to their analysis with the sensors'
      array. Furthermore, the analysis showed the adequacy of using representative
      simulated VOCs to imitate the breath of healthy and CRF states and, therefore, to
      train the sensors' array the pertinent breath signatures. The excellent
      discrimination between the various breath states obtained in this study provides
      expectations for future capabilities for diagnosis, detection, and screening
      various stages of kidney disease, especially in the early stages of the disease,
      where it is possible to control blood pressure and protein intake to slow the
      progression.

PMID- 19397335
TI  - An efficient one-pot, three-component synthesis of 5-hydrazinoalkylidene
      rhodanines from 1,2-diaza-1,3-dienes.
AB  - A novel three-component synthesis of 5-hydrazinoalkylidene rhodanine derivatives
      starting from aliphatic primary amines, carbon disulfide, and 1,2-diaza-1,3
      dienes is described. The reaction proceeds successfully under both solution and
      solid-phase conditions.

PMID- 19397336
TI  - Fabrication and electrochemical characterization of TiO2 three-dimensional
      nanonetwork based on peptide assembly.
AB  - The three-dimensional network of TiO(2) hollow nanoribbons designed from a
      peptide assembly using atomic layer deposition is demonstrated as a promising Li
      secondary battery electrode in this study. The nanoribbon network ensures
      effective transport of electrons and Li ions due to (i) a well-connected network
      of nanoribbons and (ii) the hollow structure of each nanoribbon itself, into
      which Li ions in the electrolyte can readily diffuse. The improved specific
      capacity, rate capability, and cyclability of the nanonetwork show that the
      utilization of a nanonetwork of individual hollow ribbons can serve as a
      promising strategy toward the development of high-performance electrode for Li
      secondary batteries.

PMID- 19397337
TI  - Enantioselective aza-Darzens reaction catalyzed by a chiral phosphoric acid.
AB  - Aza-Darzens reaction of ethyl diazoacetate with aldimines, derived from phenyl
      glyoxal, furnished cis-aziridine carboxylates with excellent enantioselectivities
      by means of a chiral phosphoric acid.

PMID- 19397341
TI  - A conversation with Robert Langer: pioneering biomedical scientist and engineer.
      Interview by Paul S. Weiss.

PMID- 19397338
TI  - Augmenter of liver regeneration: substrate specificity of a flavin-dependent
      oxidoreductase from the mitochondrial intermembrane space.
AB  - Augmenter of liver regeneration (ALR) is both a growth factor and a sulfhydryl
      oxidase that binds FAD in an unusual helix-rich domain containing a redox-active
      CxxC disulfide proximal to the flavin ring. In addition to the cytokine form of
      ALR (sfALR) that circulates in serum, a longer form, lfALR, is believed to
      participate in oxidative trapping of reduced proteins entering the mitochondrial
      intermembrane space (IMS). This longer form has an 80-residue N-terminal
      extension containing an additional, distal, CxxC motif. This work presents the
      first enzymological characterization of human lfALR. The N-terminal region
      conveys no catalytic advantage toward the oxidation of the model substrate
      dithiothreitol (DTT). In addition, a C71A or C74A mutation of the distal
      disulfide does not increase the turnover number toward DTT. Unlike Erv1p, the
      yeast homologue of lfALR, static spectrophotometric experiments with the human
      oxidase provide no evidence of communication between distal and proximal
      disulfides. An N-terminal His-tagged version of human Mia40, a resident
      oxidoreductase of the IMS and a putative physiological reductant of lfALR, was
      subcloned and expressed in Escherichia coli BL21 DE3 cells. Mia40, as isolated,
      shows a visible spectrum characteristic of an Fe-S center and contains 0.56 +/-
      0.02 atom of iron per subunit. Treatment of Mia40 with guanidine hydrochloride
      and triscarboxyethylphosphine hydrochloride during purification removed this
      chromophore. The resulting protein, with a reduced CxC motif, was a good
      substrate of lfALR. However, neither sfALR nor lfALR mutants lacking the distal
      disulfide could oxidize reduced Mia40 efficiently. Thus, catalysis involves a
      flow of reducing equivalents from the reduced CxC motif of Mia40 to distal and
      then proximal CxxC motifs of lfALR to the flavin ring and, finally, to cytochrome
      c or molecular oxygen.

PMID- 19397342
TI  - Integrating nanoscience into the classroom: perspectives on nanoscience education
      projects.
AB  - The National Nanotechnology Initiative has motivated substantial growth in
      nanoscience and nanotechnology research in the United States and beyond. One of
      the central goals of the National Nanotechnology Initiative is the development
      and education of future generations of nanoscience researchers. This Nano Focus
      provides a brief history of nanoscience education, including curricula that have
      been implemented successfully into secondary and college institutions, as
      described in the symposium "Integrating Nanoscience into the College and High
      School Classroom" at the 237th American Chemical Society National Meeting in
      March 2009.

PMID- 19397343
TI  - Spatial control of chemistry on the inside and outside of inorganic nanocrystals.
AB  - The ability to make inorganic nanocrystals of controlled size, shape, and
      composition is well-established for some elements and compounds, but by no means
      has been generalized to the entire periodic table. A new paper in this issue of
      ACS Nano offers a route to explore more of the periodic table with increased
      control over both composition and position for inorganic nanostructures. This
      Perspective provides a snapshot of the major challenges in controlling the
      positions of atoms and molecules both in the cores and on the surfaces of
      inorganic nanocrystals.

PMID- 19397344
TI  - Nanopore-based biosensors: the interface between ionics and electronics.
AB  - Techniques for translating the binding or the activity of single molecules
      directly into electrical signals are of interest for both fundamental and applied
      science. A paper in this issue describes experiments in which the ionic current
      through a biological nanopore is employed both to control and to monitor the
      attachment of individual DNA polymerase enzymes to their binding site on a single
      DNA molecule. This Perspective briefly sketches some of the factors that
      ultimately limit the performance of such nanoscale sensors, emphasizing in
      particular the interface between nanofluidic systems and external control
      electronics.

PMID- 19397345
TI  - Transparent TiO2 nanotube electrodes via thin layer anodization: fabrication and
      use in electrochromic devices.
AB  - In the present work, we describe an anodization process that is able to fully
      transform a thin Ti metal layer on a conductive glass into a TiO(2) nanotubular
      array. Under optimized conditions, nanotube electrodes can be obtained that are
      completely transparent and defect-free and allow electrochromic switching. These
      electrochromic electrodes show remarkable properties and can be directly
      integrated into devices.

PMID- 19397346
TI  - Internal surface modification of MFI-type zeolite membranes for high selectivity
      and high flux for hydrogen.
AB  - MFI-type zeolite membranes were modified by depositing molecular silica at a
      small number of active sites in the internal surface by in situ catalytic
      cracking of silane precursor. The limited silica deposition reduced the effective
      size of the zeolitic channels that dramatically enhanced the H(2) selectivity
      without causing a large increase in H(2) transport resistance. The modified
      zeolite membrane achieved an extraordinary H(2)/CO(2) permselectivity of 141 with
      a high H(2) permeance of 3.96 x 10(-7) mol/m(2) x s x Pa at 723 K. The effect of
      pore modification on the gas transport behavior was studied on the basis of
      single gas permeation data.

PMID- 19397347
TI  - Organic field effect transistor using pentacene single crystals grown by a liquid
      phase crystallization process.
AB  - Nearly perfect pentacene single crystals with wide terraces several micrometers
      in width were grown by crystallization from a pentacene-containing
      trichlorobenzene solution. Organic field-effect transistors (OFETs) were
      fabricated with the pentacene single crystals and characterized for their
      electrical properties. The field effect mobility was found to be in the range of
      0.4-0.6 cm(2)/V x s, which is comparable to that of OFETs fabricated with
      pentacene single crystals prepared by a physical vapor-phase growth method. The
      results described in this paper clearly demonstrate that the crystallization of
      organic semiconductors from solution is a promising chemical method for device
      processing of OFETs.

PMID- 19397349
TI  - Consolidation of charged colloids during drying.
AB  - We consider the drying of latex dispersions containing submicrometer-sized
      particles dispersed in water. It is well known that the consolidation of
      colloidal particles is influenced by a number of factors such as particle size
      and shape and interparticle potential. In this work, we focus on the effect of
      surface charge on the consolidation front. Recent experimental and theoretical
      investigations on the sedimentation of charged colloidal spheres have shown that
      the large mass difference between noninteracting colloids and ions sets up a
      macroscopic electric field, thereby enhancing the diffusivity of the particles
      and resulting in an inflated sedimentation profile. Our experimental measurements
      of the concentration profile during drying-induced consolidation also reveal
      similar charge effects. We present a model for the consolidation of charged
      particles that accounts for the presence of an induced external electric field.
      As expected, the predicted particle diffusivity is enhanced by the onset of the
      electric field at low particle concentration. Fluorescence and bright-field
      microscopy were used to detect the particle concentration variation in a
      dispersion dried in a capillary, and the measured profile agrees with the
      prediction confirming the influence of particle charge on consolidation.

PMID- 19397348
TI  - Lipid-assisted formation and dispersion of aqueous and bilayer-embedded nano-C60.
AB  - Lipid assemblies provide a biocompatible approach for preparing aqueous
      nanoparticles. In this work, dipalmitoylphosphatidylcholine (DPPC) was used to
      assist in the formation and dispersion of C(60) and nano-C(60) aggregates using a
      modified reverse phase evaporation (REV) method. This method led to the rapid
      formation of aqueous nano-C(60) at DPPC/C(60) molar ratios from 500:1 to 100:1
      (12-38 nm; verified by cryogenic transmission electron microscopy), which were
      present in the bulk phase and encapsulated within vesicles. In addition to
      forming nanoparticles, C(60) was trapped within the vesicle bilayer and led to a
      reduction in the lipid melting temperature. Solvent extraction was used to
      isolate nano-C(60) from the lipids and bilayer-embedded C(60). Our results
      suggest that bilayer-embedded C(60) was present as molecular C(60) and as small
      amorphous nano-C(60) (2.3 +/- 0.4 nm), which clustered in the aqueous phase after
      the lipids were extracted. In addition to developing a new technique for nano
      C(60) formation, our results suggest that the lipid bilayer may be used as a
      hydrophobic region for dispersing and assembling small nano-C(60).

PMID- 19397350
TI  - Friction at the liquid/liquid interface of two immiscible polymer films.
AB  - We studied the friction between two immiscible polymer melts of polybutadiene
      (PBD) and polydimethylsiloxane (PDMS). Polymer films (100-300 nm thick) were
      coated onto smooth mica substrates, and then were brought into contact and
      sheared (slid) to and fro in a surface forces apparatus (SFA). Stop-wait-start
      experiments were also carried out at different sliding velocities to investigate
      the characteristic relaxation times of the interdigitation and disinterdigitation
      processes at both the static and shearing interfaces. By virtue of their limited
      interdigitation/interpenetration across the contact interface, immiscible
      polymers never fully coalesce into a continuous homogeneous material. This
      affects both their dynamic adhesion and friction forces. The immiscible interface
      exhibits various "characteristic" parameters such as its static and dynamic
      widths and at least two relaxation times: the static interpenetration time and
      the velocity adaptation time. The interfacial width saturates at some small but
      finite value, resulting in Stribeck-like behavior for the friction force as a
      function of the sliding velocity, characterized by F having a minimum value at
      some characteristic sliding velocity V. The presence of solvents at the
      immiscible interface can have a dramatic effect on the friction or lubrication
      forces. The implications of the results regarding the depth and dynamics of
      interdigitation and interpenetration of immiscible chains across an interface are
      discussed in relation to the adhesion, friction, and strength of polymer
      composites and the coalescence of immiscible droplets.

PMID- 19397352
TI  - Density functional theory study of the binding of glycine, proline, and
      hydroxyproline to the hydroxyapatite (0001) and (0110) surfaces.
AB  - In view of the importance of the hydroxyapatite/collagen composite of both
      natural bone tissue and in synthetic biomaterials, we have investigated the
      interaction of three constituent amino acids of the collagen matrix with two
      major hydroxyapatite surfaces. We have employed electronic structure techniques
      based on the density functional theory to study a range of different binding
      modes of the amino acids glycine, proline, and hydroxyproline at the
      hydroxyapatite (0001) and (0110) surfaces. We have performed full geometry
      optimizations of the hydroxyapatite surfaces with adsorbed amino acid molecules
      to obtain the optimum substrate/adsorbate structures and interaction energies.
      The calculations show that the amino acids are capable of forming multiple
      interactions with surface species, particularly if they can bridge between two
      surface calcium ions. The binding energies range from 290 kJ mol(-1) for glycine
      on the (0001) surface to 610 kJ mol(-1) for hydroxyproline on the (0110) surface.
      The large adsorption energies are due to a wide range of interactions between the
      adsorbate and surface, including proton transfer from the adsorbates to surface
      OH or PO(4) groups. Hydroxyproline binds most strongly to the surfaces, but all
      three amino acids should be good sites for the nucleation and growth of the
      hydroxyapatite (0110) surface at the collagen matrix.

PMID- 19397351
TI  - Self-assembly of tobacco mosaic virus at oil/water interfaces.
AB  - The oil/water interfacial assembly of tobacco mosaic virus (TMV) has been studied
      in situ by tensiometry and small-angle X-ray and neutron scattering (SAXS and
      SANS). TMV showed different orientations at the perfluorodecalin/water interface,
      depending on the initial TMV concentration in the aqueous phase. At low TMV
      concentration, the rods oriented parallel to the interface, mediating the
      interfacial interactions at the greatest extent per particle. At high TMV
      concentrations, the rods were oriented normal to the interface, mediating the
      interfacial interactions and also neutralizing inter-rod electrostatic repulsion.
      We found that the inter-rod repulsive forces between TMVs dominated the in-plane
      packing, which was strongly affected by the ionic strength and the bulk solution
      but not by the pH in the range of pH = 6-8.

PMID- 19397353
TI  - Adsorption-enhanced hydrolysis of beta-1,4-glucan on graphene-based amorphous
      carbon bearing SO3H, COOH, and OH groups.
AB  - The reaction mechanism of the hydrolysis of cellulose by a carbon-based solid
      acid, amorphous carbon containing graphene sheets bearing SO(3)H, COOH, and
      phenolic OH groups, has been investigated in detail through the hydrolysis of
      water-soluble beta-1,4-glucan. Whereas a range of solid strong Bronsted acid
      catalysts (inorganic oxides with acidic OH groups, SO(3)H-bearing resins, and the
      carbon-based solid acid) can hydrolyze the beta-1,4-glycosidic bonds in
      cellobiose (the shortest water-soluble beta-1,4-glucan), the tested solid acids
      except for the carbon material, consisting of conventional solid acids, cannot
      function as effective catalysts for the hydrolysis of cellohexaose (a long-chain
      water-soluble beta-1,4-glucan). However, the carbon material exhibits remarkable
      catalytic performance for the hydrolysis of cellohexaose: the turnover frequency
      (TOF) of SO(3)H groups in the carbon material exceeds ca. 20 times those of the
      conventional solid acids, reaching that of sulfuric acid, which is the most
      active catalyst. Experimental results revealed that inorganic oxides with acidic
      OH groups are not acidic enough to decompose the hydrogen and beta-1,4-glycosidic
      bonds in cellohexaose molecules aggregated by strong hydrogen bonds as well as
      cellulose and that the SO(3)H groups of the resins that do not adsorb beta-1,4
      glucan are unable to attack the hydrogen and beta-1,4-glycosidic bonds in
      cellohexaose molecules effectively. In contrast, the carbon material is capable
      of adsorbing beta-1,4-glucan by phenolic OH or COOH groups in the carbon
      material, and SO(3)H groups bonded to the carbon therefore function as effective
      active sites for both decomposing the hydrogen bonds and hydrolyzing the beta-1,4
      glycosidic bonds in the adsorbed long-chain water-soluble beta-1,4-glucan
      aggregate. These results suggest that the synergetic combination of high
      densities of the functional groups bonded to amorphous carbon causes the
      efficient hydrolysis of beta-1,4-glucan, including cellulose, on the carbon
      material.

PMID- 19397354
TI  - Influence of film-substrate adhesion on the mechanical properties of thin polymer
      films.
AB  - The mechanical properties of mechanical double layers (thin amorphous films of
      poly(n-butyl methacrylate) on considerably stiffer silicon substrates) were
      investigated by force-displacement curves acquired with an atomic force
      microscope. The substrate surface was modified to provide a hydrophilic and a
      hydrophobic moiety. Such a modification affects the adhesion between film and
      substrate, since the polymer film adheres strongly on the hydrophilic side and
      weakly on the hydrophobic one. In this way, we were able to investigate the
      influence of the adhesion between the polymer film and substrate on the
      mechanical properties of the mechanical double layer. We were able to show that
      force-displacement curves on the two moieties of the sample have a different
      shape, and we propose an interpretation of the mechanisms determining the force
      deformation curves on films with small adhesion to the substrate. This experiment
      can also provide an approach to the question of how the mechanical properties of
      a bulk material change with the volume to surface ratio, since a film with
      vanishing adhesion to the substrate is the only experimental accessible setup
      approximating a free-standing thin film.

PMID- 19397355
TI  - Ultraflat templated polymer surfaces.
AB  - The roughness of spin-cast polymer films arises from thermally activated
      capillary waves during preparation and typically amounts to about 0.5 nm(rms)
      measured on a micrometer-sized surface area. Templating from atomically flat mica
      substrates allows the creation of polymer films with a surface roughness
      approaching the molecular scale. Three regimes of spatial frequencies are
      identified in which the roughness is controlled by different physical mechanisms.
      We find that frozen-in elastic pressure waves ultimately limit the flatness of
      polymer films.

PMID- 19397356
TI  - Assembly of purple membranes on polyelectrolyte films.
AB  - The membrane protein bacteriorhodopsin in its native membrane bound form (purple
      membrane) was adsorbed and incorporated into polyelectrolyte multilayered films,
      and adsorption was in situ monitored by optical waveguide light-mode
      spectroscopy. The formation of a single layer or a double layer of purple
      membranes was observed when adsorbed on negatively or positively charged
      surfaces, respectively. The purple membrane patches adsorbed on the
      polyelectrolyte multilayers were also evidenced by atomic force microscopy
      images. The driving forces of the adsorption process were evaluated by varying
      the ionic strength of the solution as well as the purple membrane concentration.
      At high purple membrane concentration, interpenetrating polyelectrolyte loops
      might provide new binding sites for the adsorption of a second layer of purple
      membranes, whereas at lower concentrations only a single layer is formed.
      Negative surfaces do not promote a second protein layer adsorption. Driving
      forces other than just electrostatic ones, such as hydrophobic forces, should
      play a role in the polyelectrolyte/purple membrane layering. The subtle interplay
      of all these factors determines the formation of the polyelectrolyte/purple
      membrane matrix with a presumably high degree of orientation for the incorporated
      purple membranes, with their cytoplasmic, or extracellular side toward the bulk
      on negatively or positively charged polyelectrolyte, respectively. The structural
      stability of bacteriorhodopsin during adsorption onto the surface and
      incorporation into the polyelectrolyte multilayers was investigated by Fourier
      transform infrared spectroscopy in attenuated total reflection mode. Adsorption
      and incorporation of purple membranes within polyelectrolyte multilayers does not
      disturb the conformational majority of membrane-embedded alpha-helix structures
      of the protein, but may slightly alter the structure of the extramembraneous
      segments or their interaction with the environment. This high stability is
      different from the lower stability of the predominantly beta-sheet structures of
      numerous globular proteins when adsorbed onto surfaces.

PMID- 19397357
TI  - Model-independent analysis of QCM data on colloidal particle adsorption.
AB  - Quartz crystal microbalance (QCM) is widely used for studying soft interfaces in
      liquid environment. Many of these interfaces are heterogeneous in nature, in the
      sense that they are composed of discrete, isolated entities adsorbed at a
      surface. When characterizing such interfaces, one is interested in determining
      parameters such as surface coverage and size of the surface-adsorbed entities.
      The current strategy is to obtain this information by fitting QCM data--shifts in
      resonance frequency, DeltaF, and bandwidth, DeltaGamma--with the model derived
      for smooth, homogeneous films using the film acoustic thickness and shear elastic
      moduli as fitting parameters. Investigating adsorption of liposomes and
      icosahedral virus particles on inorganic surfaces of titania and gold, we
      demonstrate that the predictions of this model are at variance with the
      experimental observations. In particular, while the model predicts that the ratio
      between the bandwidth and frequency shifts, DeltaGamma/DeltaF (the Df ratio),
      should increase with both surface coverage and particle size, we observe that
      this ratio increases with increasing particle size but decreases with increasing
      surface coverage, demonstrating that QCM response in heterogeneous films, such as
      those composed of adsorbed colloidal particles, does not conform with the
      predictions of the homogeneous film model. Employing finite element method (FEM)
      calculations, we show that hydrodynamic effects are the cause of this
      discrepancy. Finally, we find that the size of the adsorbed colloidal particles
      can be recovered from a model-independent analysis of the plot of the
      DeltaGamma/DeltaF ratio versus the frequency shift on many overtones.

PMID- 19397358
TI  - Float and compress: honeycomb-like array of a highly stable protein scaffold.
AB  - Organizing nano-objects, proteins in particular, on surfaces is one of the
      primary goals of bio/chemical nanotechnology. A highly stable protein scaffold
      (6His-SP1) was organized into a hexagonal 2D array by a new, versatile method.
      The protein was expelled from solution into the air/water interface and
      compressed in a Langmuir trough into a closely packed monolayer without the use
      of phospholipids or other surfactants at the interface. The 2D arrays formed at
      the air/water interface were characterized by transmission electron microscopy
      (TEM) and atomic force microscopy (AFM).

PMID- 19397359
TI  - Shear-induced isotropic to nematic transition of liquid-crystal polymers:
      identification of gap thickness and slipping effects.
AB  - The shear-induced isotropic-nematic transition is a generic property of liquid
      crystalline polymer melts which is identified by the emergence in the isotropic
      phase of a strong birefringence above a critical shear rate. Although
      spectacular, this transition cannot be explained on the basis of a conventional
      approach (coupling with pretransitional fluctuations or with viscoelastic
      relaxation times). We investigate the asymptotic rheo-optical behavior of the
      shear-induced phase. The sample is an unentangled cyanobiphenyl side-chain
      polyacrylate. We show that the birefringence increases almost linearly and then
      saturates above a given shear rate depending on the gap thickness. Similarly, the
      shear stress versus shear rate curve exhibits for the same thickness and using
      the same substrate (quartz), an overshoot occurring at about the same shear rates
      followed by the stress plateau (indicating a stress-optical equivalence). In
      contrast, when the substrate is different, the stress-optical equivalence is no
      more valid. We interpret the overshoot and the plateau observed in birefringence
      and in shear stress curves as the entrance in a so far unidentified macroscopic
      sliding regime. The slipping mechanism is corroborated by the recent
      identification of macroscopic long-range correlations in unentangled polymer melt
      and contrasts with a description in terms of a nucleation-growth process as in
      wormlike micellar solutions.

PMID- 19397360
TI  - One-pot synthesis of water-stable ZnO nanoparticles via a polyol hydrolysis route
      and their cell labeling applications.
AB  - ZnO nanoparticles have been identified as a new generation of biofriendly cell
      labeling agents since they are nontoxic, less expensive, and chemically stable in
      air. However, ZnO nanoparticles show poor water stability due to high equilibrium
      concentration of Zn species in water in a wide pH range. In this work, a one-pot
      polyol hydrolysis method was developed for synthesizing water-stable ZnO
      nanoparticles with blue emission. The as-synthesized ZnO nanoparticles were
      hydrophilic and stable in water, even at basic or acidic aqueous conditions. The
      PL properties of the ZnO nanoparticles stored at various pH values (i.e., 4.5-11)
      could be preserved for at least 3 days. The good water stability of the ZnO
      nanoparticles was offered by the surface attachment of an ester compound, which
      was formed as a result of the reaction between the stearic acid and triethylene
      glycol (TREG). This method provides a new approach to synthesize water-stable ZnO
      nanoparticles. The resultant ZnO nanoparticles demonstrated promising
      applications in cell labeling.

PMID- 19397361
TI  - Swelling in water of a layered alkali silicate, octosilicate, modified with a
      sulfonic Acid group.
AB  - A layered alkali silicate, octosilicate (Na(2)Si(8)O(17) x nH(2)O), was
      functionalized with sulfonic acid to impart swelling ability in water. To
      immobilize the sulfonic acid group on octosilicate, (3
      mercaptopropyl)trimethoxysilane was attached in the interlayer space and
      subsequently oxidized. Surface coverage with the sulfonic acid group (0.7, 1.3,
      and 1.7 groups per Si(8)O(17)) was controlled by changing the added amount of the
      silane coupling reagent (0.7, 1.3, and 2.0 groups per Si(8)O(17)). The sulfonated
      octosilicates hydrated to expand the interlayer space, where the degree of
      expansion varied with the surface coverage of sulfonic acid. For the sulfonated
      octosilicate with the lowest surface coverage (0.7 group per Si(8)O(17)), the
      remaining interlayer silanol group was efficiently grafted with the
      trimethylsilyl group to expand the interlayer space further upon hydration. The
      effect of the electrolyte concentration on the hydration of the sulfonated
      octosilicates was investigated to find that with the increase in NaCl
      concentration the basal spacing decreased. The sulfonated and trimethylsilylated
      octosilicates were dispersed in water to form colloidal suspensions with varied
      transparency.

PMID- 19397362
TI  - pH-Dependent encapsulation of pyrene in PPI-core:PAMAM-shell dendrimers.
AB  - Core-shell dendrimers consisting of poly(propyleneimine) (PPI) dendrimer as a
      core and poly(amidoamine) (PAMAM) dendrons as a shell have been synthesized
      through the route of Michael addition reaction followed by amidation. These
      macromolecules were investigated their ability to solubilize a guest molecule,
      pyrene. The number of encapsulated pyrene molecules per dendrimer increased with
      pH of a solution and generation (G) of PAMAM dendron, and it reached 2.7 for
      PPI(G3)-core:PAMAM(G3)-shell dendrimer at pH 11. It was confirmed that the
      solubilized pyrene located in the hydrophobic nanocavities of the PPI dendrimer
      core in the dendrimer. The shrunk PAMAM dendron shell should play a role of
      retention fence of doped molecules.

PMID- 19397363
TI  - Template synthesis and adsorption properties of hierarchically porous zirconium
      titanium oxides.
AB  - Hierarchical morphologies in metal oxides are advantageous for many applications,
      including controlled drug release, photocatalysis, catalysis, synthetic
      biomaterials, and adsorption and separation technologies. In this study, agarose
      gel has been used as a template to prepare zirconium titanium mixed oxide pellets
      with bimodal porosity. Sol-gel chemistry conducted within the agarose gel
      produced "coral-like" interconnected networks of oxide nanoparticles with
      controllable quantities of zirconium and titanium. The materials were
      characterized using N(2) sorption, extended X-ray absorption fine structure, X
      ray diffraction, TEM, SEM, zeta potential, and thermogravimetric analysis (to
      measure surface hydroxyl group density). The oxides were then tested for the
      adsorption of vanadyl and vanadate to determine which Zr mole fraction exhibited
      the highest capacity and fastest kinetics. The material containing 25 mol % Zr
      exhibited the highest surface area (322 +/- 8 m(2)/g) of the compositions
      investigated and also displayed a superior adsorption rate and capacity. Vanadate
      adsorption occurred with faster kinetics than did vanadyl adsorption. A
      comparative study demonstrated that the macro/meso pore structure had improved
      transport properties over a monomodal mesopore structure of similar Zr/Ti
      composition. The faster vanadate adsorption kinetics is attributed to enhanced
      surface accessibility in a hierarchical material.

PMID- 19397364
TI  - Influence of superheated water on the hydrogen bonding and crystallography of
      piperazine-based (Co)polyamides.
AB  - Here we demonstrate that superheated water is a solvent for polyamide 2,14 and
      piperazine-based copolyamides up to a piperazine content of 62 mol %. The
      incorporation of piperazine allows for a variation of the hydrogen bond density
      without altering the crystal structure (i.e., the piperazine units cocrystallize
      with the PA2,14 units (Hoffmann, S.; Vanhaecht, B.; Devroede, J.; Bras, W.;
      Koning, C. E.; Rastogi, S. Macromolecules 2005, 38, 1797-1803). It is shown that
      the crystallization of PA2,14 from superheated water greatly influences the
      crystal structure. Water molecules incorporated in the PA2,14 crystal lattice
      cause a slip on the hydrogen bonded planes, resulting in a coexistence of a
      triclinic and a monoclinic crystal structure. On heating above the Brill
      transition, the water molecules exit from the lattice, restoring the triclinic
      crystal structure. With increasing piperazine content, and hence decreasing
      hydrogen bond density, the dissolution temperature decreases. It is only possible
      to grow single crystals from superheated water up to a piperazine content of 62
      mol %. For these single crystals, the incorporation of water molecules in the
      vicinity of the amide group is seen by the presence of COO- stretch vibrations
      with FTIR spectroscopy. These vibrations disappear on heating above the Brill
      transition temperature, and the water molecules leave the amide groups. For
      copolyamides with more than 62 mol % piperazine, no Brill transition is observed,
      no single crystals can be grown from water, and no water molecules are observed
      in the vicinity of the amide groups (Vinken, E.; Terry, A. E.; Hoffmann, S.;
      Vanhaecht, B.; Koning, C. E.; Rastogi, S. Macromolecules 2006, 39, 2546-2552).
      The high piperazine content (co)polyamides have fewer hydrogen bond donors and
      are therefore less likely to have interactions with the water molecules. This
      work demonstrates the relation among the Brill transition, the dissolution of
      polyamide in superheated water, and its influence on the hydrogen bonds and the
      amide groups.

PMID- 19397365
TI  - Patterning of HeLa cells on a microfabricated Au-coated ITO substrate.
AB  - HeLa cells were patterned on a microfabricated Au-coated ITO substrate. Part of
      the Au film was dissolved by the electrochemical wet stamping technique, and the
      substrate was then immersed in a thiol-terminated methoxy-poly(ethylene glycol)
      (mPEG-SH) solution for further modification. Self-assembled monolayers (SAMs) on
      the gold island can form cell- and protein-resistant regions on the substrate,
      and living HeLa cells can adhere to the exposed ITO surface. Single cell patterns
      could be achieved when the size of a microstructure unit matched that of the
      cell. The fluorescence experiments further proved that living HeLa cells prefer
      to attach to the ITO substrate rather than the mPEG-SH-modified gold islands.

PMID- 19397366
TI  - An unusually stable G-quadruplex within the 5'-UTR of the MT3 matrix
      metalloproteinase mRNA represses translation in eukaryotic cells.
AB  - MT3-MMP is a matrix metalloproteinase involved in the regulation of cancer cell
      invasion and metastasis. The MT3-MMP mRNA contains a 20-nucleotide G-rich region
      (M3Q) upstream of the initiation codon. Herein, we report that the M3Q purine
      only sequence forms an extremely stable intramolecular G-quadruplex structure and
      has an inhibitory role on translation of a reporter gene in eukaryotic cells. The
      formation of the G-quadruplex structure was indicated by circular dichroism (CD)
      spectroscopy and enzymatic footprinting with RNase T1. The unusual stability of
      the G-quadruplex was evidenced when addition of only 1 mM KCl resulted in about a
      30 degrees C increase in the melting temperature (T(m)), as compared to that
      obtained in the absence of added salt. The T(m) was independent of the RNA
      concentration, suggesting an intramolecular G-quadruplex structure. Additionally,
      in a dual luciferase reporter assay performed in eukaryotic cells, the M3Q motif
      present in the context of the entire 5'-UTR of MT3-MMP repressed activity of its
      downstream gene by more than half. To the best of our knowledge, the naturally
      occurring M3Q sequence forms one of the most stable, intramolecular RNA G
      quadruplexes reported. This report is the first to establish a functional role of
      a G-quadruplex forming sequence within the MT3-MMP 5'-UTR in the regulation of
      translation in eukaryotic cells.

PMID- 19397367
TI  - Photosynthetic system in Blastochloris viridis revisited.
AB  - The bacterium Blastochloris viridis carries one of the simplest photosynthetic
      systems, which includes a single light-harvesting complex that surrounds the
      reaction center, membrane soluble quinones, and a soluble periplasmic protein
      cytochrome c(2) that shuttle between the reaction center and the bc(1) complex
      and act as electron carriers, as well as the ATP synthase. The close arrangement
      of the photosynthetic membranes in Bl. viridis, along with the extremely tight
      arrangement of the photosystems within these membranes, raises a fundamental
      question about the diffusion of the electron carriers. To address this issue, we
      analyzed the structure and response of the Bl. viridis photosynthetic system to
      various light conditions, by using a combination of electron microscopy, whole
      cell cryotomography, and spectroscopic methods. We demonstrate that in response
      to high light intensities, the ratio of both cytochrome c(2) and bc(1) complexes
      to the reaction centers is increased. The shorter membrane stacks, along with the
      notion that the bc(1) complex is located at the highly curved edges of these
      stacks, result in a smaller average distance between the reaction centers and the
      bc(1) complexes, leading to shorter pathways of cytochrome c(2) between the two
      complexes. Under anaerobic conditions, the slow diffusion rate is further
      mitigated by keeping most of the quinone pool reduced, resulting in a
      concentration gradient of quinols that allows for a constant supply of theses
      electron carriers to the bc(1) complex.

PMID- 19397368
TI  - Coexpression of human alpha- and circularly permuted beta-globins yields a
      hemoglobin with normal R state but modified T state properties.
AB  - For the first time, a circularly permuted human beta-globin (cpbeta) has been
      coexpressed with human alpha-globin in bacterial cells and shown to associate to
      form alpha-cpbeta hemoglobin in solution. Flash photolysis studies of alpha
      cpbeta show markedly biphasic CO and O(2) kinetics with the amplitudes for the
      fast association phases being dominant due the presence of large amounts of high
      affinity liganded hemoglobin dimers. Extensive dimerization of liganded but not
      deoxygenated alpha-cpbeta was observed by gel chromatography. The rate constants
      for O(2) and CO binding to the R state forms of alpha-cpbeta are almost identical
      to those of native HbA (k'(R(CO)) approximately 5.0 microM(-1) s(-1); k'(R(O(2)))
      approximately 50 microM(-1) s(-1)), and the rate of O(2) dissociation from fully
      oxygenated alpha-cpbeta is also very similar to that observed for HbA (k(R(O(2)))
      approximately 21-28 s(-1)). When the equilibrium deoxyHb form of alpha-cpbeta is
      reacted with CO in rapid mixing experiments, the observed time courses are
      monophasic and the observed bimolecular association rate constant is
      approximately 1.0 microM(-1) s(-1), which is intermediate between the R state
      rate measured in partial photolysis experiments (approximately 5 microM(-1) s(
      1)) and that observed for T state deoxyHbA (k'(T(CO)) approximately 0.1 to 0.2
      microM(-1) s(-1)). Thus the deoxygenated permutated beta subunits generate an
      intermediate, higher affinity, deoxyHb quaternary state. This conclusion is
      supported by equilibrium oxygen binding measurements in which alpha-cpbeta
      exhibits a P(50) of approximately 1.5 mmHg and a low n-value (approximately 1.3)
      at pH 7, 20 degrees C, compared to 8.5 mmHg and n approximately 2.8 for native
      HbA under identical, dilute conditions.

PMID- 19397369
TI  - On-bead screening of combinatorial libraries: reduction of nonspecific binding by
      decreasing surface ligand density.
AB  - On-bead screening of one-bead-one-compound (OBOC) libraries provides a powerful
      method for the rapid identification of active compounds against molecular or
      cellular targets. However, on-bead screening is susceptible to interference from
      nonspecific binding, which results in biased screening data and false positives.
      In this work, we have found that a major source of nonspecific binding is derived
      from the high ligand loading on the library beads, which permits a macromolecular
      target (e.g., a protein) to simultaneously interact with multiple ligands on the
      bead surface. To circumvent this problem, we have synthesized a phosphotyrosyl
      (pY)-containing peptide library on spatially segregated TentaGel microbeads,
      which feature a 10-fold reduced peptide loading on the bead surface but a normal
      peptide loading in the bead interior. The library was screened against a panel of
      10 Src homology 2 (SH2) domains including those of Csk and Fyn kinases and
      adaptor protein SLAP, and the specific recognition motif(s) was successfully
      identified for each of the domains. In contrast, when the SH2 domains were
      screened against a control library that contained unaltered (high) ligand loading
      at the bead surface, six of them exhibited varying degrees of sequence biases,
      ranging from minor perturbation in the relative abundance of different sequences
      to the exclusive selection of false positive sequences that have no measurable
      affinity to the target protein. These results indicate that reduction of the
      ligand loading on the bead surface represents a simple, effective strategy to
      largely eliminate the interference from nonspecific binding, while preserving
      sufficient amounts of materials in the bead interior for compound identification.
      This finding should further expand the utility of OBOC libraries in biomedical
      research.

PMID- 19397370
TI  - Total synthesis of (-)-acutumine.
AB  - The first total synthesis of the tetracyclic alkaloid (-)-acutumine is described.
      Key reactions include an asymmetric ketone allylation mediated by Nakamura's
      chiral allylzinc reagent, an anionic oxy-Cope rearrangement, and the Lewis acid
      promoted cyclization of an amine onto an alpha,beta-unsaturated dimethyl ketal.

PMID- 19397371
TI  - Mechanism and transition-state structures for nickel-catalyzed reductive alkyne
      aldehyde coupling reactions.
AB  - The mechanism of nickel-catalyzed reductive alkyne-aldehyde coupling reactions
      has been investigated using density functional theory. The preferred mechanism
      involves oxidative cyclization to form the nickeladihydrofuran intermediate
      followed by transmetalation and reductive elimination. The rate- and selectivity
      determining oxidative cyclization transition state is analyzed in detail. The d -
      > pi*(perpendicular) back-donation stabilizes the transition state and leads to
      higher reactivity for alkynes than alkenes. Strong Lewis acids accelerate the
      couplings with both alkynes and alkenes by coordinating with the aldehyde oxygen
      in the transition state.

PMID- 19397372
TI  - Does feed composition affect oxidation of rainbow trout (Oncorhynchus mykiss)
      during frozen storage?
AB  - Rainbow trout ( Oncorhynchus mykiss ) were fed a diet containing either fish oil
      or rapeseed oil and with or without 200 mg/kg carotenoid (either astaxanthin or
      canthaxanthin). A total of six diets were obtained: (1) fish oil/astaxanthin; (2)
      vegetable oil/astaxanthin; (3) fish oil/canthaxanthin; (4) vegetable
      oil/canthaxanthin; (5) fish oil/no pigment; and (6) vegetable oil/no pigment. The
      fish were slaughtered and stored in polyethylene bags individually as butterfly
      fillets for up to 22 months at -20  degrees C. The composition of the fish muscle
      at slaughter and during frozen storage was evaluated by sampling after 4, 8, 13,
      18, and 22 months. The carotenoid content in the muscle was found to be
      approximately 9-10 mg/kg of fish for both carotenoids. Primary oxidation lipid
      products (peroxides) as well as secondary oxidation products (volatiles) were
      measured. In addition, the level of protein carbonyl groups and the content of
      tocopherols and carotenoids in the muscle were also measured. To estimate the
      overall changes in sensory properties of the different samples during storage, a
      trained sensory panel also evaluated the samples. Both the sensory panel and the
      chemical analysis revealed that in this investigation fish fed fish oil were
      slightly more oxidized than fish fed vegetable oil. Results showed that
      canthaxanthin effectively protected both protein and lipid against oxidation
      during frozen storage. In contrast, astaxanthin did not seem to have a clear and
      systematic effect. Results indicated that the feed composition influenced the
      fish muscle composition and subsequently the oxidative stability of the fish
      during frozen storage. Besides, other constituents in the feed might influence
      deposition of antioxidants in the tissue and consequently affect the oxidative
      stability of the muscle.

PMID- 19397373
TI  - Sulfonamido-phosphoramidite ligands in cooperative dinuclear hydrogenation
      catalysis.
AB  - Sulfonamido-phosphoramidite ligands lead to the formation of Rh-Rh dinuclear
      complexes through the anionic P-N(-) bridging character. The resulting "boat
      shaped" dinuclear catalysts activate molecular H(2) through a cooperative
      dinuclear endocyclic mechanism, resulting in one bridging and one classical
      hydride on the dinuclear complex. These new complexes are very active
      hydrogenation catalysts that operate via a new cooperative hydrogenation
      activation mechanism, as calculated with density functional theory, and they
      display unequaled high selectivities in the hydrogenation of hindered cyclic
      acetamidoalkenes.

PMID- 19397374
TI  - Ureic nitrogen transformation in multi-layer soil columns treated with urease and
      nitrification inhibitors.
AB  - The use of N-(n-butyl)thiophosphoric triamide (NBPT), as a urease inhibitor, is
      one of the most successful strategies utilized to increase the efficiency of urea
      based fertilization. To date, NBPT has been added to the soil incorporated in
      fertilizers containing either urea or the inhibitor at a fixed percentage on the
      urea weight. The possibility of using NBPT physically separated from urea-based
      fertilizers could make its use more flexible. In particular, a granulated product
      containing NBPT could be utilized in soils treated with different urea-based
      fertilizers including livestock urine, the amount depending on soil
      characteristics and/or the urea source (e.g., mineral fertilizer, organo-mineral
      fertilizer, or animal slurry). In this study, a multilayer soil column device was
      used to investigate the influence of an experimental granular product (RV)
      containing NBPT and a garlic extract, combining the ability to protect NBPT by
      oxidation and nitrification inhibition activity, on (a) spatial variability of
      soil urease and nitrification activities and (b) timing of urea hydrolysis and
      mineral-N form accumulation (NO(2)(-), NO(3)(-), NH(4)(+)) in soil treated with
      urea. The results clearly demonstrated that RV can, effectively, inhibit the soil
      urease activity along the soil column profile up to 8-10 cm soil layer depth and
      that the inhibition power of RV was dependent on time and soil depth. However,
      nitrification activity is not significantly influenced by RV addition. In
      addition, the soil N transformations were clearly affected by RV; in fact, RV
      retarded urea hydrolysis and reduced the accumulation of NH(4)(+)-N and NO(2)(-)
      N ions along the soil profile. The RV product was demonstrated to be an
      innovative additive able to modify some key ureic N trasformation processes
      correlated with the efficiency of the urea-based fertilization, in a soil column
      higher than 10 cm.

PMID- 19397375
TI  - Assessing the phytoavailability of dieldrin residues in charcoal-amended soil
      using tenax extraction.
AB  - Consecutive and single Tenax extractions were applied to characterize the
      effectiveness of activated charcoal (AC) amendments to reduce the
      phytoavailability of dieldrin in a natively contaminated horticultural soil.
      Dieldrin desorption from untreated and 800 mg(AC) kg(-1) soil was well described
      by a model with three dieldrin fractions of different kinetics: a rapidly
      (F(rap)), slowly (F(slow)), and very slowly (F(v.slow)) desorbing fraction. The
      AC amendment resulted in a transfer of dieldrin from the F(slow) to the F(v.slow)
      fraction. The F(v.slow) increased by nearly 10% compared to the control soil.
      Dieldrin extractability by Tenax from AC amended soils was not influenced by the
      cultivation of cucumber plants indicating the stability of this remediation
      technique. Dieldrin extractability by Tenax at the beginning of plant growth
      correlated only weakly with the dieldrin content of the cucumbers at harvest.
      Therefore, the potential of Tenax extractions to predict the uptake of dieldrin
      by cucumbers appears to be limited.

PMID- 19397376
TI  - Revisiting automated G-protein coupled receptor modeling: the benefit of
      additional template structures for a neurokinin-1 receptor model.
AB  - The feasibility of automated procedures for the modeling of G-protein coupled
      receptors (GPCR) is investigated on the example of the human neurokinin-1 (NK1)
      receptor. We use a combined method of homology modeling and molecular docking and
      analyze the information content of the resulting docking complexes regarding the
      binding mode for further refinements. Moreover, we explore the impact of
      different template structures, the bovine rhodopsin structure, the human beta(2)
      adrenergic receptor, and in particular a combination of both templates to include
      backbone flexibility in the target conformational space. Our results for NK1
      modeling demonstrate that model selection from a set of decoys can in general not
      solely rely on docking experiments but still requires additional mutagenesis
      data. However, an enrichment factor of 2.6 in a nearly fully automated approach
      indicates that reasonable models can be created automatically if both available
      templates are used for model construction. Thus, the recently resolved GPCR
      structures open new ways to improve the model building fundamentally.

PMID- 19397377
TI  - Long-term memory for the terrorist attack of September 11: flashbulb memories,
      event memories, and the factors that influence their retention.
AB  - More than 3,000 individuals from 7 U.S. cities reported on their memories of
      learning of the terrorist attacks of September 11, as well as details about the
      attack, 1 week, 11 months, and/or 35 months after the assault. Some studies of
      flashbulb memories examining long-term retention show slowing in the rate of
      forgetting after a year, whereas others demonstrate accelerated forgetting. This
      article indicates that (a) the rate of forgetting for flashbulb memories and
      event memory (memory for details about the event itself) slows after a year, (b)
      the strong emotional reactions elicited by flashbulb events are remembered
      poorly, worse than nonemotional features such as where and from whom one learned
      of the attack, and (c) the content of flashbulb and event memories stabilizes
      after a year. The results are discussed in terms of community memory practices.

PMID- 19397378
TI  - Duration sensitivity depends on stimulus familiarity.
AB  - When people are asked to assess or compare the value of experienced or
      hypothetical events, one of the most intriguing observations is their apparent
      insensitivity to event duration. The authors propose that duration insensitivity
      occurs when stimuli are evaluated in isolation because they typically lack
      comparison information. People should be able to evaluate the duration of stimuli
      in isolation, however, when stimuli are familiar and evoke comparison
      information. The results of 3 experiments support the hypothesis. Participants
      were insensitive to the duration of hypothetical (Experiment 1) and real
      (Experiment 2) unfamiliar experiences but sensitive to the duration of familiar
      experiences. In Experiment 3, participants were insensitive to the duration of an
      unfamiliar noise when it was unlabeled but sensitive to its duration when it was
      given a familiar label (i.e., a telephone ring). Rather than being a unique
      phenomenon, duration neglect (and perhaps other forms of scope insensitivity)
      appears to be a particular case of insensitivity to unfamiliar attributes.

PMID- 19397379
TI  - Automatic optimism: the affective basis of judgments about the likelihood of
      future events.
AB  - People generally judge that the future will be consistent with their desires, but
      the reason for this desirability bias is unclear. This investigation examined
      whether affective reactions associated with future events are the mechanism
      through which desires influence likelihood judgments. In 4 studies, affective
      reactions were manipulated for initially neutral events. Compared with a neutral
      condition, events associated with positive reactions were judged as likely to
      occur, and events associated with negative reactions were judged as unlikely to
      occur. Desirability biases were reduced when participants could misattribute
      affective reactions to a source other than future events, and the relationship
      between affective reactions and judgments was influenced when approach and
      avoidance motivations were independently manipulated. Together, these findings
      demonstrate that positive and negative affective reactions to potential events
      cause the desirability bias in likelihood judgments and suggest that this effect
      occurs because of a tendency to approach positive possibilities and avoid
      negative possibilities.

PMID- 19397380
TI  - Influence of peripheral and motivational cues on rigid-flexible functioning:
      Perceptual, behavioral, and cognitive aspects.
AB  - Recent research has shown that performing approach versus avoidance behaviors
      (arm flexion vs. extension) effectively influences cognitive functioning. In
      another area, lateralized peripheral activations (left vs. right side) of the
      motivational systems of approach versus avoidance were linked to various
      performances in cognitive tasks. By combining these 2 avenues of research, the
      influence of motor behaviors on flexible thinking was examined through the use of
      lateralized approach or/and avoidance behaviors. In 5 experiments reported in
      this article, a combination of the laterality and arm flexion versus extension
      variables successfully determined flexibility-rigidity functioning, consistent
      with the motor congruence hypothesis (J. Cretenet & V. Dru, 2004). Through these
      experiments, this result has been replicated with perceptual, behavioral, and
      cognitive aspects of flexibility, contributing to a better understanding of the
      relationships between bodily components, affect, and cognition.

PMID- 19397381
TI  - A common-coding account of the bidirectional evaluation-behavior link.
AB  - Three experiments tested the influence of approach- and avoidance-related lever
      movements on the perception of masked affectively positive and negative stimuli.
      A motivational account of the bidirectional evaluation-behavior link predicted an
      enhanced detection of response-compatible stimuli, whereas a common-coding model
      predicted a reduced evaluative sensitivity toward such stimuli due to feature
      binding conflicts. The results consistently supported the common-coding
      explanation. In Experiment 1, detection (d') of positive and negative stimuli was
      selectively impaired by the generation of congruent approach- and avoidance
      related lever movements, respectively. This effect, referred to as action-valence
      blindness, was replicated in Experiment 2 and shown to depend on the evaluative
      meaning of the generated movement rather than on the movement per se. Experiment
      3 revealed that action-valence blindness depends on a temporal overlap between
      movement generation and stimulus evaluation. A common-coding link between
      evaluation and motor behavior is discussed.

PMID- 19397382
TI  - Event boundaries in perception affect memory encoding and updating.
AB  - Memory for naturalistic events over short delays is important for visual scene
      processing, reading comprehension, and social interaction. The research presented
      here examined relations between how an ongoing activity is perceptually segmented
      into events and how those events are remembered a few seconds later. In several
      studies, participants watched movie clips that presented objects in the context
      of goal-directed activities. Five seconds after an object was presented, the clip
      paused for a recognition test. Performance on the recognition test depended on
      the occurrence of perceptual event boundaries. Objects that were present when an
      event boundary occurred were better recognized than other objects, suggesting
      that event boundaries structure the contents of memory. This effect was strongest
      when an object's type was tested but was also observed for objects' perceptual
      features. Memory also depended on whether an event boundary occurred between
      presentation and test; this variable produced complex interactive effects that
      suggested that the contents of memory are updated at event boundaries. These data
      indicate that perceptual event boundaries have immediate consequences for what,
      when, and how easily information can be remembered.

PMID- 19397383
TI  - Empty sets as part of the numerical continuum: conceptual precursors to the zero
      concept in rhesus monkeys.
AB  - The goal of the current research was to explore whether monkeys possess
      conceptual precursors necessary for understanding zero. We trained rhesus monkeys
      on a nonsymbolic numerical matching-to-sample task, and on a numerical ordering
      task. We then introduced nondifferentially reinforced trials that contained empty
      sets to determine whether monkeys would treat empty sets as numerical values. All
      monkeys successfully matched and ordered the empty sets without any training.
      Accuracy showed distance effects, indicating that they treated empty sets as
      values on a numerical continuum.

PMID- 19397384
TI  - Parallel response selection disrupts sequence learning under dual-task
      conditions.
AB  - Some studies suggest that dual-task processing impairs sequence learning; others
      suggest it does not. The reason for this discrepancy remains obscure. It may have
      to do with the dual-task procedure often used. Many dual-task sequence learning
      studies pair the serial reaction time (SRT) task with a tone-counting secondary
      task. The tone-counting task, however, is not ideal for studying the cognitive
      processes involved in sequence learning. The present experiments sought to
      identify the nature of the interference responsible for disrupting sequence
      learning in dual-task situations using more tractable dual-task procedures.
      Experiments 1 and 2 showed that parallel-interfering central processing disrupts
      sequence learning. Experiment 3 used a novel combination of the SRT task as the
      secondary task in a psychological refractory period procedure. It showed that SRT
      task performance can be disrupted without disrupting sequence learning when that
      disruption involves a response-selection bottleneck rather than parallel response
      selection. Together, these results suggest that it is the overlap of central
      processes involved in successfully performing the 2 tasks concurrently that leads
      to learning deficits in dual-task sequence learning.

PMID- 19397385
TI  - Testing signal-detection models of yes/no and two-alternative forced-choice
      recognition memory.
AB  - The current study compared 3 models of recognition memory in their ability to
      generalize across yes/no and 2-alternative forced-choice (2AFC) testing. The
      unequal-variance signal-detection model assumes a continuous memory strength
      process. The dual-process signal-detection model adds a thresholdlike
      recollection process to a continuous familiarity process. The mixture signal
      detection model assumes a continuous memory strength process, but the old item
      distribution consists of a mixture of 2 distributions with different means. Prior
      efforts comparing the ability of the models to characterize data from both test
      formats did not consider the role of parameter reliability, which can be critical
      when comparing models that differ in flexibility. Parametric bootstrap
      simulations revealed that parameter regressions based on separate fits of each
      test type only served to identify the least flexible model. However, simultaneous
      fits of receiver-operating characteristic data from both test types with goodness
      of-fit adjusted with Akaike's information criterion (AIC) successfully recovered
      the true model that generated the data. With AIC and simultaneous fits to real
      data, the unequal-variance signal-detection model was found to provide the best
      account across yes/no and 2AFC testing.

PMID- 19397386
TI  - Segmentation in reading and film comprehension.
AB  - When reading a story or watching a film, comprehenders construct a series of
      representations in order to understand the events depicted. Discourse
      comprehension theories and a recent theory of perceptual event segmentation both
      suggest that comprehenders monitor situational features such as characters'
      goals, to update these representations at natural boundaries in activity.
      However, the converging predictions of these theories had previously not been
      tested directly. Two studies provided evidence that changes in situational
      features such as characters, their locations, their interactions with objects,
      and their goals are related to the segmentation of events in both narrative texts
      and films. A 3rd study indicated that clauses with event boundaries are read more
      slowly than are other clauses and that changes in situational features partially
      mediate this relation. A final study suggested that the predictability of
      incoming information influences reading rate and possibly event segmentation.
      Taken together, these results suggest that processing situational changes during
      comprehension is an important determinant of how one segments ongoing activity
      into events and that this segmentation is related to the control of processing
      during reading.

PMID- 19397387
TI  - Serotonin-depleted rats are capable of learning in active place avoidance, a
      spatial task requiring cognitive coordination.
AB  - Neurotransmitter substrate of spatial cognition belongs to current topics in
      behavioral neuroscience. The present study examined the effects of serotonin
      depletion with p-chlorophenylalanine on learning of rats in active place
      avoidance, a spatial task requiring allothetic mapping and cognitive coordination
      and highly dependent upon hippocampus. Serotonin depletion transiently increased
      locomotor activity in response to footshocks, but it did not change the avoidance
      efficiency measured by three spatial parameters. These results suggest that
      serotonin neurotransmission is not crucial for cognitive coordination and
      allothetic learning, i.e. the processes, which are crucial for active place
      avoidance performance.

PMID- 19397388
TI  - Parvalbumin and TRPV1 receptor expression in dorsal root ganglion neurons after
      acute peripheral inflammation.
AB  - Expression of parvalbumin (PV) and transient receptor potential vanilloid (TRPV1)
      receptors in the lumbar dorsal root ganglion neurons (DRG) was evaluated in
      control animals and in rats after acute carageenan-induced knee joint
      inflammation. PV is a calcium binding protein that acts as a calcium buffer,
      affects intracellular calcium homeostasis and may thus influence signal
      transduction and synaptic transmission. TRPV1 receptors are viewed as molecular
      integrators of nociceptive stimuli and modulate spinal cord synaptic transmission
      beside their function in the peripheral nerve endings. In naive rats, 13 % of the
      L4 DRG neurons had PV immunopositivity (PV+) and 36 % expressed TRPV1 receptors
      (TRPV1+). The soma of the PV+ neurons was of medium to large size, while the
      TRPV1 receptors were expressed in small diameter neurons. The co-localization of
      the PV and TRPV1 immunoreactivity was minimal (0.2 %). There was no significant
      change in the PV+ (11 %), TRPV1+ (42 %) and PV+TRPV1+ (0.25 %) expression, or
      shift in the neuronal size distribution 28 h after the unilateral peripheral
      inflammation, both when compared to controls and when ipsilateral to
      contralateral sides were evaluated. Thus under the given experimental conditions,
      no change in somatic TRPV1 receptors and PV expression in L4 DRG neurons was
      found.

PMID- 19397389
TI  - Comparison of the electrothermal vessel-sealing system versus endoclip in
      laparoscopic appendectomy.
AB  - BACKGROUND: Various techniques have been used for the division of mesoappendix,
      such as endoloops, endoscopic linear cutting staplers, an electrothermal vessel
      sealing system (LigaSure), the Harmonic Scalpel, clips, and bipolar coagulation.
      In the present study, LigaSure and an endoclip were compared in laparoscopic
      appendectomy (LA). MATERIALS AND METHODS: This study included patients who
      underwent LA for acute appendicitis at Istanbul University, Cerrahpasa Medical
      Faculty, Emergency Unit (Istanbul, Turkey) between May 2003 and April 2007. The
      patients were assigned to two groups according to the mesoappendix dissection
      device: LigaSure and endoclip groups. The main outcome measures (e.g., operating
      time, conversion rate, hospital stay, postoperative complications, etc.) were
      then compared. RESULTS: LA was performed in 280 patients with acute appendicitis.
      LigaSure and endoclips were used in 127 and 153 patients, respectively. The mean
      operative times were 41 and 54 minutes in the LigaSure and endoclip groups,
      respectively. Conversions to open rates were found to be 9.4% (12 patients) in
      the LigaSure and 11.1% (17 patients) in endoclip groups. No statistically
      significant differences regarding hospital stay or complications were found,
      whereas significant differences were observed in surgical time and conversion
      rate. CONCLUSION: The use of LigaSure facilitates the dissection of mesoappendix
      and shortens the operation time in LA. We believe that LigaSure is a safe, useful
      tool for mesoappendix dissection.

PMID- 19397390
TI  - Robotic radical prostatectomy for patients with locally advanced prostate cancer
      is feasible: results of a single-institution study.
AB  - OBJECTIVES: The aim of this study was to compare the outcomes of robotic
      prostatectomy (RP) in patients with clinically localized or locally advanced
      prostate cancer (PC). PATIENTS AND METHODS: Between July 2005 and February 2008,
      we performed RP in 357 patients by using the da Vinci robot system and a
      transperitoneal approach. We defined locally advanced PC as cases with a clinical
      T-stage >/=T3a with any serum prostate-specific antigen (PSA) or Gleason score.
      Among the 321 men not treated with neoadjuvant hormonal therapy, 200 patients had
      clinically localized PC and 121 patients had locally advanced PC. We compared
      perioperative variables and early surgical outcomes between the two groups.
      RESULTS: Although advanced PC patients had significantly higher mean preoperative
      PSA levels, prostatectomy Gleason scores, and extracapsular extension rates,
      there were no significant differences in mean operation time, estimated blood
      loss, duration of bladder catheterization, hospital stay, or initiation of a
      regular postoperative diet between the two groups. Except for some early cases, a
      bilateral extended lymphadenectomy was performed without difficulty in both
      groups. Although both the frequency of lymph node invasion and the positive
      surgical margin rates were higher in the advanced PC patients, the positive
      surgical margin rate (48.8%) in the present study was similar to those of open
      radical retropubic prostatectomy in other studies. The overall complication rate
      did not differ between the two groups. Two intraoperative rectal injuries
      occurred in patients with locally advanced PC and were closed primarily without
      specific problems, except for 1 case. CONCLUSIONS: Our results suggest that RP
      may be performed safely on patients with locally advanced PC.

PMID- 19397391
TI  - The correlation between reactive oxygen species and histopathology of the liver,
      gut, and kidneys in animals with elevated intra-abdominal pressure.
AB  - BACKGROUND: Clinical and experimental studies have shown that the laparoscopic
      procedure provides a typical model of ischemia-reperfusion injury in the organs
      by oxygen-derived free radicals. A pneumoperitoneum produces ischemia during
      insufflation and reperfusion during desufflation. The aim of this study was to
      assess the causative role of free radical-mediated reactions in tissue damage
      under different intra-abdominal insufflation pressures. MATERIALS AND METHODS:
      Thirty five mature New Zealand white rabbits were assigned to three groups of 10
      animals. In groups 1, 2, and 3, the designated pressures of 10, 15, and 20 mm Hg,
      respectively. The remaining 5 animals underwent laparotomy, using a 10-cm midline
      incision taken as group 4 (control). Blood samples were collected before (0
      minutes) and at the end of the procedure (60 minutes). After the collection of
      the last blood samples, all animals were sacrificed and the samples from the
      liver, kidney, and gut were obtained for histologic evaluation and also
      measurements of tissue malondialdehyde (MDA) levels. RESULTS: The nitric oxide
      levels were not changed in groups 1 and 2, but increased significantly in group
      3. Tissue MDA levels were significantly higher in groups 1 and 2 than groups 3
      and 4. Histopathologic examination of the kidney revealed some findings of
      reversible hypoxic cell injury, including acute cellular swelling, vascular
      congestion, and some early findings of irreversible injury, such as lysis of the
      cytoplasmic membrane in all groups and focal parancymal bleeding area in only
      group 3 as a consequence of increased pressure. Liver histology revealed cellular
      swelling and karyorhexis in hepatocytes in group 1, whereas only congestion and
      sinusoidal dilatation was observed in groups 2 and 3. CONCLUSION: Our
      experimental study showed that abdominal insufflation causes ischemia and free
      radical production, which seems responsible for the cell damage that occured
      during laparoscopic surgery.

PMID- 19397392
TI  - Effects of long chain omega-3 fatty acids on metalloproteinases and their
      inhibitors in combined dyslipidemia patients.
AB  - We evaluate the effect of a standardized dietary supplementation with omega-3
      polyunsaturated fatty acids (n-3 PUFAs) on the level of some markers of vascular
      remodeling in patients with combined dyslipidemia. Three hundred and thirty-three
      patients received placebo or n-3 PUFAs for 6 months. We evaluated body mass
      index, glycemic profile, blood pressure, lipid profile, lipoprotein(a),
      plasminogen activator inhibitor-1, homocysteine, fibrinogen, high-sensitivity C
      reactive protein, ADP, MMP-2 and MMP-9, and tissue inhibitors of
      metalloproteinase-1 and -2. A significant increase of high-density lipoprotein
      cholesterol, and a significant decrease of triglycerides were present after 3 and
      6 months with n-3 PUFAs intake. A significant plasminogen activator inhibitor-1,
      fibrinogen and high-sensitivity C reactive protein decrease was obtained after 3
      and 6 months and a significant ADP increase was observed after 3 and 6 months of
      n-3 PUFAs. A significant MMP-2, MMP-9, tissue inhibitors of metalloproteinase-1
      and tissue inhibitors of metalloproteinase-2 decrease was obtained after 6 months
      compared to the baseline value with n-3 PUFAs intake. n-3 PUFAs give a better
      lipid profile and a better improvement of coagulation, fibrinolytic and
      inflammatory parameters than placebo. Furthermore, lowers levels of MMP-2, MMP-9
      and their tissue inhibitors are obtained with n-3 PUFAs compared to placebo.

PMID- 19397393
TI  - The use of bedside diagnostic laparoscopy in the intensive care unit.
AB  - BACKGROUND: The clinical evaluation of the abdomen in intensive care (ICU)
      patients who are intubated can be very complex. Many bedside diagnostic tests are
      available to assist the clinician, including ultrasound, peritoneal lavage, and
      plain X-rays. However, in the ICU setting, these tests can be unreliable. An
      abdominal computed tomography (CT) scan is more reliable, but it requires
      transportation to the Radiology Department, which can be risky. In this paper, we
      present our experience with bedside laparoscopy in the general ICU population.
      METHODS: Between April 2004 and November 2007, 35 adult patients (19 male, 16
      female), with a mean age of 69 years (range, 39-83), underwent bedside diagnostic
      laparoscopy (DL) in the ICU. Hemodynamic and ventilatory parameters as well as
      the time required for the DL and CT scan procedure were compared. In addition,
      the ASA, APACHE II, and SOFA scores were documented. RESULTS: Laparoscopic
      findings were negative for intra-abdominal disease in 57.1% (n = 20) patients.
      The remaining patients (42.9%; n = 15) had positive laparoscopic findings for
      intra-abdominal disease. The overall mortality rate in our group of patients was
      60%. The time required for DL was less (21.8 +/- 7.6 minutes) than the time
      required for a CT scan (38.2 +/- 6.2 minutes; P < 0.05). Three patients went on
      to have a therapeutic procedure in the ICU. CONCLUSION: The evaluation of the
      critically ill patient for intra-abdominal pathology with DL is a practical
      solution and needs to be used more frequently in this setting. In this paper, we
      present our experience with diagnostic laparoscopy in the ICU and found it to be
      safe and, in certain cases, may have a potential role as a bedside therapeutic
      tool. Although a number of reports with small series of patients have addressed
      the benefits and feasibility of DL, it is still being underutilized in the ICU. A
      more aggressive attempt should be made to incorporate DL as a routine procedure
      in the ICU.

PMID- 19397394
TI  - Functional evaluation at 1-year follow-up of laparoscopic Nissen-Rossetti
      fundoplication.
AB  - Laparoscopic Nissen fundoplication is currently the gold standard for surgical
      treatment of gastroesophageal reflux disease. The aim of this study was to
      present our experience with this procedure at 1 year of follow-up. Forty patients
      were operated on between January 2006 and July 2007, and 30 underwent a 24-hour
      postoperative pH-metry study. Ninety-two percent of the patients were
      asymptomatic at a follow-up of 12 months. All pH-metric parameters improved.
      DeMeester and Johnson's score was reduced from 44.7 to 7.75; endoscopy with
      histologic samples revealed the healing of esophagitis in all patients; 4 (13%)
      patients complained of dysphagia, which resolved within 1 month after surgery.
      Twenty-seven (90%) patients were completely satisfied by their surgical results.
      One year after surgery, 24-hour ph-metric results show that laparoscopic Nissen
      fundoplication can completely control acid reflux with relatively few
      complications and a high degree of patient satisfaction.

PMID- 19397395
TI  - Video-assisted laparoscopic extracorporeal appendectomy versus open appendectomy.
AB  - OBJECTIVES: Laparoscopic appendectomy (LA) is categorized into intracorporeal
      appendectomy (ICA) and video-assisted extracorporeal appendectomy (VAECA). This
      study is conducted to compare feasibility and effectiveness of video-assisted
      extracorporeal appendectomy (VAECA) with open appendectomy (OA). PATIENTS AND
      METHODS: This was a comparative descriptive study conducted at the Department of
      Surgery of Liaquat University of Medical and Health Sciences (Jamshoro, Pakistan)
      from June 2003 to November 2007. Two hundred and eighty-three patients of acute
      appendicitis were included and categorized into two groups: A and B. Group A
      included 150 (53%) patients operated on by the OA technique, while group B
      included 133 (47%) patients in whom VAECA was performed. VAECA was accomplished
      through three ports in the majority of patients (89%), while a few cases (11%)
      were completed by two ports only. Patients below 10 years of age and with
      suspected appendicular mass were excluded from the study. Both operative
      techniques and their merits and demerits were explained to all the patients and,
      depending upon their choice or by a simple flip of a coin, they were operated on
      by either of the techniques. A well-informed written consent was also taken from
      every patient. The results of both the groups were collected on a proforma and
      were compared in terms of cosmesis, total operative time, operative and
      postoperative complications, and total duration of hospital stay. RESULTS: The
      mean operating time was much shorter in group B (p < 0.001), compared to group A
      patients. The incidence of postoperative infection was comparatively higher in
      OA, compared to VAECA. The rate of operative complications (p < 0.001),
      postoperative complications (p < 0.01), and duration of hospital stay (p < 0.001)
      were all significantly lower in the VAECA group. Cosmetic results were excellent
      in VAECA, compared to OA, as assessed by length of incision and the postoperative
      scar formation. CONCLUSION: VAECA can be a good alternate option in simple cases
      without much adhesions or mass formation.

PMID- 19397396
TI  - Laparoscopic transabdominal preperitoneal hernia repair (TAPP): stapling the mesh
      is not mandatory.
AB  - BACKGROUND: This report reviews our experience with 104 transabdominal
      preperitoneal (TAPP) hernia repairs, using a selective staple-free technique,
      over the period April 2003 to July 2007 (50 months). MATERIALS AND METHODS:
      Ninety-one patients underwent TAPP repair (13 bilateral). Eighty-one were males
      and 10 females. Mean age was 61 years. There have been 58 right inguinal hernias
      and 46 left. We had 47 indirect, 42 direct, 6 pantaloon, 4 supravesicular, 3
      inguinal-scrotal, 2 sliding, and 1 femoral hernia. Twenty-three of the hernias we
      repaired were recurrences. We used a modified staple-free technique with the
      placement of a 15 x 10 cm polypropylene mesh in the preperitoneal space with
      sutured peritoneal closure. The mesh was stapled selectively only in very large
      defects (nine repairs; 9%). We used nondisposable instruments and trocars.
      RESULTS: We had no conversions. Mean operative time was 47 min/repair with a mean
      hospitalization of 1.2 nights. We had 1 recurrence (mean follow-up, 34 months).
      Postoperative complications were: preperitoneal hematoma 1, urinary retention 1,
      and inguinal seromas/hematomas 11. Mean return to normal activities was 7 days.
      CONCLUSIONS: TAPP repair is a technically demanding laparoscopic technique, but
      once mastered, is safe and effective with a high degree of patient satisfaction.
      Stapling the mesh is not necessary in most cases, thus resulting in a remarkably
      low cost. The rapid rehabilitation typically associated with laparoscopic surgery
      was seen in all our patients. The low recurrence rate (1% in our series) compares
      favorably to other tension-free techniques.

PMID- 19397397
TI  - Abdominal access in gynaecologic laparoscopy: a comparison between direct optical
      and open access.
AB  - BACKGROUND: More than 50% of major laparoscopic complications occur during the
      initial entry into the abdomen. We investigated the efficacy and the safety of
      two laparoscopic access techniques: the direct optical access (DOA) versus the
      classical open entry, as described by Hasson. MATERIALS AND METHODS: Two hundred
      and two premenopausal women, homogeneous in age, parity, and body mass index
      undergoing laparoscopic surgery for simple ovarian cysts, were prospectively,
      randomly assigned to either open or DOA abdominal entry for laparoscopic surgery.
      The following parameters were compared: duration of access for entry into the
      abdomen, occurrence of vascular and/or bowel injury, and blood loss. The results
      were analyzed by using SAS software (SAS Institute, Inc., Cary, NC), considering
      a P-value of <0.05 as significant. RESULTS: No statistically significant
      differences were observed in the occurrence of major vascular and/or bowel injury
      between the two techniques. However, time for establishment of abdominal entry
      was significantly reduced in the DOA group, as was the blood loss (P < 0.05).
      CONCLUSIONS: The results of this preliminary comparison on the DOA and the Hasson
      methods, commonly used by general surgeons and less frequently by gynecologists,
      suggest that the visual entry system confers a little statistical advantage over
      the traditional Hasson entry, in terms of safety, minimal time saving, and in
      reducing blood loss, allowing a safe, fast, visually guided entry.

PMID- 19397398
TI  - Apical interactions of HIV type 1 with polarized HEC-1 cell monolayer modulate R5
      HIV type 1 spread by submucosal macrophages.
AB  - The in vitro model of HIV-1 transcytosis through a monolayer of HEC-1 cells is
      thought to mimic the mucosal crossing of the virus that may occur in vivo. We
      evaluated whether the stimulation of HEC-1 by HIV may modulate HIV infection of
      macrophages. Thus, the ability to capture, produce, and transfer R5 viruses to T
      cells, attract T cells, and finally produce cytokines/chemokines, was compared
      between untreated macrophages (M0) and macrophages differentiated in the presence
      of medium collected at the basolateral pole of HEC-1, which were unstimulated
      [M(BL)] or stimulated with either R5-HIV-1Ba-L [M(BL-R5)] or X4-HIV-1NDK [M(BL
      X4)]. M(BL-X4)-secreted CCR5-interacting chemokines integrated and replicated HIV
      less efficiently than did M(BL) and M(BL-R5). M(BL-R5) and M(BL-X4) similarly
      transmitted HIV to activated T cells. Interestingly, mannose-binding receptors
      and heparan sulfate proteoglycans were variously involved in HIV adsorption,
      whereas DC-SIGN mostly mediated the HIV transfer. Conversely to M(BL) and M(BL
      X4), M(BL-R5) did not secrete eotaxin, GRO, ITAC, lymphotactin, MIP-1, MIP-3, and
      RANTES, which was associated with a weak capacity to recruit
      CD4(+)CXCR4(+)CCR5(+) T cells. In particular, M(BL-R5) specifically released
      soluble factors enhancing HIV production by recruited T cells. These submucosal
      conditioned macrophages differentially captured, produced, and transferred R5-HIV
      1 to T cells, according to the tropism of the virus deposited at the apical pole
      of HEC-1. These observations challenge the question of the in vivo involvement of
      HIV-1 as a supraepithelial stimulus that likely modulates the susceptibility for
      HIV-1 of submucosal target cells in favor of its transmission.

PMID- 19397399
TI  - The association of HIV infection with left ventricular mass/hypertrophy.
AB  - Left ventricular hypertrophy (LVH) is an independent predictor of major
      cardiovascular events. Cardiovascular risk is increased among human
      immunodeficiency virus (HIV)-infected patients. To assess LV mass/hypertrophy in
      HIV infection, 654 women enrolled in the Women's Interagency HIV Study underwent
      transthoracic echocardiography. There were 454 HIV-infected and 200 uninfected
      women, mean age 40.8 +/- 9.3 years. LV mass/height(2.7) was similar between the
      HIV-infected and the HIV-uninfected groups (41.4 +/- 11.1 vs. 39.9 +/- 10.3
      g/h(2.7); p = 0.37). The prevalence of LVH was similar between the two groups
      (LVH by LV mass/height(2.7) criteria 15.0% vs. 13.0%, p = 0.29). Relative wall
      thickness (RWT), defined as the ratio of LV wall thickness to cavity diameter,
      was also similar between the HIV-infected and HIV-uninfected groups (0.36 +/-
      0.05 vs. 0.37 +/- 0.06, p = 0.16). On multiple linear regression analysis
      adjusting for age, W/H ratio, triceps skinfold thickness, systolic/diastolic BP,
      diabetes, hypertension and dyslipidemia; HIV status (b = 2.08, p = 0.02, CI 0.27
      3.88); weight (b per kg = 0.15, p < 0.01, CI 0.08-0.22); and smoking duration (b
      per one-year increase = 0.08, p = 0.03, CI 0.01-0.16) were independent correlates
      of LV mass/height(2.7) (Model R(2) = 0.20, p < 0.001). Weight (aOR = 1.04, CI
      1.01-1.06) and smoking duration (aOR = 1.03, CI 1.01-1.06) were independent
      correlates of LVH. Being HIV negative, increased age, increased triceps skinfold
      thickness, and higher W/H ratio were independent correlates of higher RWT. Among
      HIV-infected women, higher LV mass was not associated with a history of AIDS
      defining illness, nadir CD4(+) count <200 cells/microl, or with the duration of
      highly active antiretroviral therapy (HAART). Women taking NRTIs had higher LV
      mass. Higher RWT was associated with current CD4(+) count. In conclusion, HIV
      infection is associated with greater LV mass but not with a higher prevalence of
      LVH. Among HIV-infected women, RWT, but not LV mass, is associated with the
      degree of immunosuppression.

PMID- 19397400
TI  - Analysis of the V1V2 region of the SIV envelope in the brains of morphine
      dependent and control SIV/SHIV-infected macaques.
AB  - Six morphine-dependent and three control macaques were infected with a mixture of
      SIV/SHIV. Half of the animals in the morphine group developed accelerated disease
      (rapid progressor) and died within 20 weeks postinfection. The evolution of the
      envelope gene in the brain of the rapid progressor and morphine-dependent group
      along with that in the control group was assessed. Six to 10 clones from the
      brain of each macaque were sequenced and were compared against each other as well
      as against a challenge virus. Analysis of the sequences revealed that the
      diversity and divergence of the clones were higher in the control group as
      compared to the morphine-dependent macaques, although this difference was not
      statistically significant.

PMID- 19397401
TI  - A novel codon insert in protease of clade B HIV type 1.
AB  - A novel combination of three codon inserts in the pol coding region of HIV-1 RNA
      was identified in a highly antiretroviral experienced study subject with HIV-1
      infection. A one codon insert was observed in the protease region between codon
      40 and 41 simultaneously with a two codon insert present in the reverse
      transcriptase region at codon 69.

PMID- 19397402
TI  - NOTES: Education and training.
AB  - The concept of minimally invasive surgery has gained widespread acceptance
      because of significant reduction in the patient postoperative morbidity that is
      associated with these surgical procedures. Natural orifice translumenal
      endoscopic surgery (NOTES) could theoretically maximize the advantages of
      minimally invasive surgery by performing intra-abdominal surgery in an
      "incisionless" manner. NOTES requires a new surgical skill set that would need to
      be taught to urologists to ensure its safe implementation. Several fundamental
      issues must be determined regarding safety and efficacy before any widespread
      implementation of this new technology to urologic surgery can be entertained. The
      development of specialized instruments designed for NOTES will certainly be
      crucial. Human ingenuity will undoubtedly succeed in this endeavor. Therefore,
      development of guidelines for training will be necessary for the safe adoption of
      this technique by urologists in their clinical practice. As previously
      demonstrated in laparoscopic surgery, a dedicated curriculum with clearly
      delineated objectives and teaching strategies will govern the success of
      postgraduate courses and residency training in urologic NOTES. These types of
      comprehensive educational programs will provide the basic foundation for the
      acquisition of the necessary knowledge and the development of the appropriate
      surgical skills. Animal and cadaveric laboratories will provide realistic
      interaction with tissue. Mentoring and surgical simulators will facilitate
      progressive acquisition and maintenance of NOTES skills in the future.

PMID- 19397403
TI  - In vivo magnetic resonance imaging of spinal cord injury in the mouse.
AB  - The feasibility of performing high-resolution in vivo magnetic resonance imaging
      (MRI) to visualize the injured mouse spinal cord using a three-dimensional (3D)
      FIESTA (fast imaging employing steady state acquisition) pulse sequence, in a
      clip compression injury model, is presented. Images were acquired using a 3-Tesla
      clinical whole-body MR system equipped with a high-performance gradient coil
      insert. High-resolution mouse cord images were used to detect and monitor the
      cord lesions for 6 weeks after spinal cord injury (SCI). The epicenter of the
      injury appeared as a region of mixed signal intensities on day 2 post-SCI.
      Regions of signal hypointensity appeared at the lesion site by 2 weeks post-SCI
      and became more apparent with time. In some mice, large cyst-like lesions were
      detected rostral to the lesion epicenter, as early as 2 weeks post-SCI, and
      increased in volume with time. In addition, MRI was used to detect and monitor
      iron-labeled mesenchymal stem cells (MSCs) after their transplantation into the
      injured cord. MSCs appeared as large, obvious regions of signal loss in the cord,
      which decreased in size over time.

PMID- 19397404
TI  - Mutations in the newly identified RAX regulatory sequence are not a frequent
      cause of micro/anophthalmia.
AB  - AIM: Microphthalmia and anophthalmia are at the severe end of the spectrum of
      abnormalities in ocular development. A few genes (SOX2, OTX2, RAX, and CHX10)
      have been implicated in isolated micro/anophthalmia, but causative mutations of
      these genes explain less than a quarter of these developmental defects. A
      specifically conserved SOX2/OTX2-mediated RAX expression regulatory sequence has
      recently been identified. We postulated that mutations in this sequence could
      lead to micro/anophthalmia, and thus we performed molecular screening of this
      regulatory element in patients suffering from micro/anophthalmia. METHODS: Fifty
      one patients suffering from nonsyndromic microphthalmia (n = 40) or anophthalmia
      (n = 11) were included in this study after negative molecular screening for SOX2,
      OTX2, RAX, and CHX10 mutations. Mutation screening of the RAX regulatory sequence
      was performed by direct sequencing for these patients. RESULTS: No mutations were
      identified in the highly conserved RAX regulatory sequence in any of the 51
      patients. CONCLUSIONS: Mutations in the newly identified RAX regulatory sequence
      do not represent a frequent cause of nonsyndromic micro/anophthalmia.

PMID- 19397405
TI  - Screening for Familial Mediterranean Fever M694V and V726A mutations in the Greek
      population.
AB  - Familial Mediterranean Fever (FMF) is an autosomal recessive genetic disease that
      primarily affects populations surrounding the Mediterranean basin. FMF patients
      suffer from recurrent episodes of fever accompanied by abdominal pain, pleuritis,
      and arthritis. Missense mutations in the gene for FMF (MEFV) have been shown to
      be responsible for the disease, while more than 70 mutations have been identified
      to date. The aim of the present study was to determine the carrier rates of two
      of the most common MEFV mutations, M694V and V726A, in the general Greek
      population. A cohort of 220 healthy and unrelated individuals of Greek descent
      was screened for the two MEFV mutations using the Amplification Refractory
      Mutation System. Our results showed that none of the healthy individuals tested
      were carriers of any of the two mutations. In conclusion, our study independently
      confirms that the carrier rate for the MEFV mutations M694V and V726A is
      extremely low in the general Greek population.

PMID- 19397406
TI  - Evaluation of the SMN and NAIP genes in a family: homozygous deletion of the SMN2
      gene in the fetus and outcome of the pregnancy.

PMID- 19397407
TI  - IL-12 as an adjuvant for the enhancement of protective humoral immunity.

PMID- 19397408
TI  - Post-transplant immunotherapy: combining cancer vaccines with hematopoietic stem
      cell transplantation.

PMID- 19397410
TI  - Quadrivalent meningococcal ACYW-135 glycoconjugate vaccine for broader protection
      from infancy.
AB  - Invasive meningococcal disease is a global public-health concern, with infants
      and adolescents bearing the majority of the disease burden. Vaccination is the
      most rational strategy to prevent meningococcal disease. Control of serogroup C
      disease has largely been achieved by the introduction of glycoconjugate
      meningococcal C vaccines, initially in the UK in 1999, and subsequently in
      several other countries. The recent licensure of a quadrivalent glycoconjugate
      vaccine against serogroups A, C, Y and W-135 in the USA and Canada has broadened
      protection against Neisseria meningitidis in 2-55 year olds. The investigational
      quadrivalent meningococcal serogroup A, C, Y and W-135 glycoconjugate vaccine
      (MenACYW-CRM197), which is immunogenic from infancy, has the potential to extend
      protection to the most vulnerable age group. This article discusses this novel
      quadrivalent vaccine formulation and its potential to control invasive disease
      caused by N. meningitidis serogroups A, C, Y and W-135.

PMID- 19397411
TI  - How to design effective vaccines: lessons from an old success story.
AB  - Evaluation of: Gaucher D, Therrien R, Kettaf N et al. Yellow fever vaccine
      induces integrated multilineage and polyfunctional immune responses. J. Exp. Med.
      205(13), 3119-3131 (2008). Despite the successful development of vaccines that
      are able to elicit potent and protective immune responses, the majority of
      vaccines were developed empirically and the mechanistic events leading to
      protective immune responses are often poorly understood. This impedes the
      development of new prophylactic as well as therapeutic vaccines for infectious
      diseases and cancer. Gaucher et al. took advantage of the effective yellow fever
      vaccine 17D to prospectively identify key immunological responses elicited by the
      vaccine using functional genomics and flow cytometric analysis. The results of
      the study clearly indicate 'that the immune response to a strong vaccine is
      preceded by the coordinated induction of master transcription factors that lead
      to the development of a broad, polyfunctional and persistent immune response
      integrating all effector cells of the immune system'.

PMID- 19397412
TI  - Opportunities and challenges of developing thermostable vaccines.
AB  - All vaccines lose potency over time and the rate of potency loss is temperature
      dependent. Therefore, cold-chain systems have been established to ensure that the
      potency of vaccines is maintained by storing them under refrigerated conditions
      (in most cases between 2 and 8 degrees C) until the point of use. This article
      aims to review the approaches being used to develop thermostable vaccine
      formulations that would be resistant to damage caused by freezing or excessive
      heat, and that could reduce dependence on the cold chain. The challenges
      associated with the implementation of these novel formulations are discussed, as
      well as the potential benefits and opportunities of taking vaccines out of the
      cold chain.

PMID- 19397413
TI  - Reaching international GMP standards for vaccine production: challenges for
      developing countries.
AB  - Standards for vaccine production have been increasing at a rapid rate. Current
      standards of good manufacturing practice (GMP) had been thought to be out of the
      reach of developing country vaccine producers, many of whom are in the public
      sector, overseen by unvalidated national regulatory authorities (NRAs). With the
      advent of the GMP regulations in 1963 and their application to vaccine
      production, even many industrialized country manufacturers with stringent NRA
      oversight had difficulties. This article assesses the ability of developing
      country manufacturers to meet GMP by the only currently available global
      indicator: WHO prequalification. As recently as 1996, no developing country NRA
      was considered able to enforce GMP compliance. That number increased to four in
      2002 and six in 2006, with a concomitant increase in the number of manufacturers
      considered to be operating to GMP standards. Examples of the difficulties faced
      by manufacturers in achieving this are given, as well as implications for the
      future vaccine market.

PMID- 19397414
TI  - Novel strategies for improved cancer vaccines.
AB  - Therapeutic vaccination against cancer is an important modality complementing
      current standard therapies and may lead to long-term control of cancer. Numerous
      strategies are in development in an attempt to achieve better effectiveness but,
      except for the recent advent of vaccines against human papillomavirus, the long
      effort to produce a cancer vaccine has not succeeded. Nevertheless, a number of
      novel approaches can be pursued that, in our view, include optimized antigen
      design, in vivo-targeted dendritic cell vaccination and cancer vaccines used in
      combination with chemotherapy, monoclonal antibodies, adoptive T-cell transfer or
      stem cell transplantation. This article summarizes the rationale and development
      of these approaches for improved cancer vaccines.

PMID- 19397415
TI  - Heterologous prime-boost vaccinations for poverty-related diseases: advantages
      and future prospects.
AB  - Classical vaccination approaches, based on a single vaccine administered in a
      homologous prime-boost schedule and optimized to induce primarily neutralizing
      antibodies, are unlikely to be sufficiently efficacious to prevent TB, malaria or
      HIV infections. Novel vaccines, capable of inducing a more powerful immune
      response, in particular T-cell immunity, are desperately needed. Combining
      different vaccine modalities that are able to complement each other and induce
      broad and sustainable immunity is a promising approach. This review provides an
      overview of heterologous prime-boost vaccination modalities currently in
      development for the 'big three' poverty-related diseases and emphasizes the need
      for innovative vaccination approaches.

PMID- 19397416
TI  - Prevention of infectious diseases in older adults through immunization: the
      challenge of the senescent immune response.
AB  - A decline in immune function with aging increases the risk of different
      infectious diseases, many of which of can be prevented by vaccination. Influenza
      is foremost among these illnesses and remains a significant problem in older
      adults despite widespread influenza vaccination programs. There are major
      challenges to developing new or more effective vaccines against influenza and the
      many other virus and bacterial illnesses that commonly affect the population aged
      over 65 years. This article will provide a summary of the impact of vaccine
      preventable diseases, including influenza, respiratory syncytial virus,
      pneumococcal disease and herpes zoster, strategies that are being used to develop
      or improve vaccines against these diseases and how this might alter the immune
      response to improve protection.

PMID- 19397417
TI  - Vero cell platform in vaccine production: moving towards cell culture-based viral
      vaccines.
AB  - The development of cell culture systems for virus propagation has led to major
      advances in virus vaccine development. Primary and diploid cell culture systems
      are now being replaced by the use of continuous cell lines (CCLs). These
      substrates are gaining increasing acceptance from regulatory authorities as
      improved screening technologies remove fears regarding their potential oncogenic
      properties. The Vero cell line is the most widely accepted CCL by regulatory
      authorities and has been used for over 30 years for the production of polio and
      rabies virus vaccines. The recent licensure of a Vero cell-derived live virus
      vaccine (ACAM2000, smallpox vaccine) has coincided with an explosion in the
      development of a range of new viral vaccines, ranging from live-attenuated
      pediatric vaccines against rotavirus infections to inactivated whole-virus
      vaccines against H5N1 pandemic influenza. These developments have illustrated the
      value of this cell culture platform in the rapid development of vaccines against
      a range of virus diseases.

PMID- 19397418
TI  - Influenza A (H5N1) pandemic prototype vaccine Fluval.
AB  - The timely development of safe and effective vaccines is likely to be the single
      most important public-health tool for decreasing the morbidity, mortality and
      economic effects of the influenza pandemic. The objective of this article is to
      provide a detailed description of the chemistry and immunogenicity of one of the
      better studied inactivated whole-virion aluminum phosphate-adjuvanted vaccines,
      Fluval (Omninvest, Hungary), while we discuss safety data of all clinical trials
      published on H5N1 vaccines to date. Fluval was chosen for detailed discussion
      owing to its immunogenicity after only one dose, the fact that it was one of the
      very first H5N1 vaccines that demonstrated the potential for dose sparing and,
      unlike all mainstream oil-in-water adjuvanted reverse genetics-derived H5N1
      vaccines, it is whole virion based.

PMID- 19397419
TI  - Update on Campylobacter jejuni vaccine development for preventing human
      campylobacteriosis.
AB  - Campylobacteriosis constitutes a serious medical and socioeconomic problem
      worldwide. Rapidly increasing antibiotic resistance of bacterial strains compels
      us to develop alternative therapeutic strategies and to search for efficient
      immunoprophylactic methods. The vast majority of Campylobacter infections in
      developed countries occur as sporadic cases, mainly caused by eating undercooked
      Campylobacter-contaminated poultry. The most efficient strategy of decreasing the
      number of human Campylobacter infections is by implementing protective
      vaccinations for humans and/or chickens. Despite more than 10 years of research,
      an effective anti-Campylobacter vaccine has not been developed. This review
      highlights our increasing knowledge of Campylobacter interaction with host cells
      and focuses on recently published data describing the efficacy of anti
      Campylobacter vaccine prototypes.

PMID- 19397421
TI  - Proteomic biomarkers for blast neurotrauma: targeting cerebral edema,
      inflammation, and neuronal death cascades.
AB  - Proteomics for blast traumatic brain injury (bTBI) research represents an
      exciting new approach that can greatly help to address the complex pathology of
      this condition. Antibody-based platforms, antibody microarrays (AbMA), and
      reverse capture protein microarrays (RCPM) can complement the classical methods
      based on 2D gel electrophoresis and mass spectrometry (2DGE/MS). These new
      technologies can address problematic issues, such as sample complexity,
      sensitivity, quantitation, reproducibility, and analysis time, which are
      typically associated with 2DGE/MS. Combined with bioinformatics analysis and
      interpretation of primary microarray data, these methods will generate a new
      level of understanding about bTBI at the level of systems biology. As biological
      and clinical knowledge and the availability of these systems become more widely
      established, we expect that AbMA and RCPM will be used routinely in clinical
      diagnostics, and also for following therapeutic progress. At the technical level,
      we anticipate that these platforms will evolve to accommodate comprehensive, high
      speed, label-free analysis on a human proteome-wide scale.

PMID- 19397422
TI  - Blast overpressure in rats: recreating a battlefield injury in the laboratory.
AB  - Blast injury to the brain is the predominant cause of neurotrauma in current
      military conflicts, and its etiology is largely undefined. Using a compression
      driven shock tube to simulate blast effects, we assessed the physiological,
      neuropathological, and neurobehavioral consequences of airblast exposure, and
      also evaluated the effect of a Kevlar protective vest on acute mortality in rats
      and on the occurrence of traumatic brain injury (TBI) in those that survived.
      This approach provides survivable blast conditions under which TBI can be
      studied. Striking neuropathological changes were caused by both 126- and 147-kPa
      airblast exposures. The Kevlar vest, which encased the thorax and part of the
      abdomen, greatly reduced airblast mortality, and also ameliorated the widespread
      fiber degeneration that was prominent in brains of rats not protected by a vest
      during exposure to a 126-kPa airblast. This finding points to a significant
      contribution of the systemic effects of airblast to its brain injury
      pathophysiology. Airblast of this intensity also disrupted neurologic and
      neurobehavioral performance (e.g., beam walking and spatial navigation
      acquisition in the Morris water maze). When immediately followed by hemorrhagic
      hypotension, with MAP maintained at 30 mm Hg, airblast disrupted
      cardiocompensatory resilience, as reflected by reduced peak shed blood volume,
      time to peak shed blood volume, and time to death. These findings demonstrate
      that shock tube-generated airblast can cause TBI in rats, in part through
      systemic mediation, and that the resulting brain injury significantly impacts
      acute cardiovascular homeostatic mechanisms as well as neurobehavioral function.

PMID- 19397423
TI  - Explosive blast neurotrauma.
AB  - Explosive blast traumatic brain injury (TBI) is one of the more serious wounds
      suffered by United States service members injured in the current conflicts in
      Iraq and Afghanistan. Some military medical treatments for blast TBI that have
      been introduced successfully in the war theater include decompressive
      craniectomy, cerebral angiography, transcranial Doppler, hypertonic resuscitation
      fluids, among others. Stateside neurosurgery, neuro-critical care, and
      rehabilitation for these patients have similarly progressed. With experience,
      military physicians have been able to clinically describe blast TBI across the
      entire severity spectrum. One important clinical finding is that a significant
      number of severe blast TBI victims develop pseudoaneurysms and vasospasm, which
      can lead to delayed decompensation. Another is that mild blast TBI shares
      clinical features with post-traumatic stress disorder (PTSD). Observations
      suggest that the mechanism by which explosive blast injures the central nervous
      system may be more complex than initially assumed. Rigorous study at the basic
      science and clinical levels, including detailed biomechanical analysis, is needed
      to improve understanding of this disease. A comprehensive epidemiological study
      is also warranted to determine the prevalence of this disease and the factors
      that contribute most to the risk of developing it. Sadly, this military-specific
      disease has significant potential to become a civilian one as well.

PMID- 19397426
TI  - Role of magnetic anchors during laparoendoscopic single site surgery and NOTES.
AB  - Evolution of minimally invasive techniques has generated an impetus in the
      surgical community to reduce the invasiveness of laparoscopic surgery. To achieve
      this goal, surgeons are either limiting the number of transabdominal trocars
      using laparoendoscopic single site surgery (LESS) or eliminating them completely
      using natural orifice translumenal endoscopic surgery (NOTES). The principle
      challenge with LESS or NOTES procedures is loss of triangulation, reduction in
      instrument working envelopes, and collision of conventional laparoscopic
      instrumentation. To overcome these limitations, surgical innovations, such as the
      use of deployable intracorporeal instrumentations, are necessary. Magnetic
      anchoring and guidance system (MAGS) technology is one approach for deployable
      instrumentation whereby intra-abdominal instruments can be maneuvered by the use
      of an external handheld magnet. Such a strategy would permit a single access port
      (either transabdominal or via a natural orifice) to serve as an entry point for
      multiple instruments. MAGS technology has thus far developed to incorporate
      instruments such as retractors, an intra-abdominal camera, and cautery
      dissectors. Continuous instrument development and rapid prototyping have created
      more robust MAGS platforms while potentially obviating the need for laparoscopic
      assistance. Animal work to date is promising with successful completion of a
      single-port nephrectomy as well as a NOTES transvaginal cholecystectomy in both
      nonsurvival and survival porcine models. As with all new technology, there will
      be an associated learning curve for these MAGS techniques that will necessitate
      more thorough elucidation before widespread use. The development of magnetically
      controlled and anchored intracorporeal surgical instruments, retractors, and
      cameras may advance surgical practice and improve patient care while meeting or
      exceeding the benefits of current-day fixed-trocar laparoscopy.

PMID- 19397427
TI  - The role of imaging and navigation for natural orifice translumenal endoscopic
      surgery.
AB  - BACKGROUND AND PURPOSE: One of the next frontiers of minimally invasive surgery
      is natural orifice translumenal endoscopic surgery (NOTES). This article focuses
      on the perspectives and limitations of imaging and navigation in NOTES soft
      tissue surgery. MATERIALS AND METHODS: Based on our in-vitro and in-vivo studies,
      with the applicability of different systems for image-guided soft-tissue
      endoscopic surgery, early experience with NOTES, and long-term experience with
      advanced endoluminal, laparoscopic robot-assisted endoscopic surgery, we
      performed a review of the literature. The aim was a critical analysis of the
      current role of imaging during NOTES. RESULTS: There are several steps/problems
      with NOTES that might be significantly alleviated by use of imaging and soft
      tissue navigation. One has to distinguish between preoperative planning and
      intraoperative imaging or navigation. NOTES represents a hybrid technique of
      laparoscopy and endoscopy with similar limitations in perception and two
      dimensional imaging; however, the use of flexible instruments increases the
      complexity with respect to the spatial orientation. This applies not only for the
      surgeon, but also for tracking devices for surgical navigation systems. Unlike
      optical navigation systems, electromagnetic and endoscopic (inside-out) tracking
      devices might be best suited to NOTES. CONCLUSION: The safe realization and
      standardization of NOTES represents a real challenge that necessitates close and
      effective interdisciplinary collaboration of surgeon, technicians, informatics,
      and endoscopic and applied industries. Image-guided soft-tissue navigation may be
      very helpful to minimize the hazards of the technically challenging procedure.

PMID- 19397424
TI  - In-vitro approaches for studying blast-induced traumatic brain injury.
AB  - Traumatic brain injury caused by explosive or blast events is currently divided
      into four phases: primary, secondary, tertiary, and quaternary blast injury.
      These phases of blast-induced traumatic brain injury (bTBI) are biomechanically
      distinct, and can be modeled in both in-vivo and in-vitro systems. The purpose of
      this review is to consider the mechanical phases of bTBI, how these phases are
      reproduced with in-vitro models, and to review findings from these models to
      assess how each phase of bTBI can be examined in more detail. Highlighted are
      some important gaps in the literature that may be addressed in the future to
      better identify the exact contributing mechanisms for bTBI. These in-vitro
      models, viewed in combination with in-vivo models and clinical studies, can be
      used to assess both the mechanisms and possible treatments for this type of
      trauma.

PMID- 19397425
TI  - Dose and chemical modification considerations for continuous cyclic AMP analog
      delivery to the injured CNS.
AB  - In this investigation, two cell-permeable synthetic analogs of cAMP, dibutyryl
      cAMP (db-cAMP) and 8-bromo-cAMP, which are widely used to elevate intracellular
      cAMP levels under experimental conditions, were investigated for their ability to
      dose-dependently improve histological and functional outcomes following
      continuous delivery in two models of incomplete spinal cord injury (SCI). The
      cAMP analogs were delivered via osmotic minipumps at 1-250 mM through an
      indwelling cortical cannula or by intrathecal infusion for up to 4 weeks after
      either a T8 unilateral over-hemisection or a C2-3 dorsolateral quadrant lesion,
      respectively. In both SCI models, continuous db-cAMP delivery was associated with
      histopathological changes that included sporadic micro-hemorrhage formation and
      cavitation, enhanced macrophage infiltration and tissue damage at regions beyond
      the immediate application site; no deleterious or beneficial effect of agent
      delivery was observed at the spinal injury site. Furthermore, these changes were
      accompanied by pronounced behavioral deficits that included an absence of
      progressive locomotor recovery, increased extensor tone, paralysis, and sensory
      abnormalities. These deleterious effects were not observed in saline-treated
      animals, in animals in which the db-cAMP dose did not exceed 1 mM, or in those
      animals that received a high dose (250 mM) of the alternative cAMP analog, 8
      bromo-cAMP. These results demonstrate that, for continuous intraparenchymal or
      intrathecal administration of cAMP analogs for the study of biological or
      therapeutic effects within the central nervous system (CNS), consideration of the
      effective concentration applied as well as the potential toxicity of chemical
      moieties on the parent molecule and/or their activity needs to be taken into
      account.

PMID- 19397428
TI  - Percutaneous nephrolithotomy under a multimodal analgesia regime.
AB  - OBJECTIVES: To evaluate the possibility of performing percutaneous
      nephrolithotomy (PCNL) under a multimodal analgesia regime. PATIENTS AND METHODS:
      During a period of 3 years, 51 patients requiring PCNL were enrolled in the
      study. All patients received a multimodal analgesic regime that included
      paracetamol, a COX(2) inhibitor, epidural morphine, and infiltration of the
      surgical field with local anesthetics. Percutaneous renal tract access was
      created with ultrasound guidance. All patients were informed about the
      possibility of experiencing short periods of discomfort or pain, and all patients
      completed a visual analog pain scale questionnaire postoperatively. RESULTS: All
      51 patients completed the study, and the procedure was well tolerated.
      Intraoperative problems or postoperative complications were attributed mainly to
      the procedure itself (PCNL) rather than to the analgesic regimen administered. We
      observed no morphine-related side effects. Patients were transferred directly
      back to the ward immediately after the operation. The use of analgesics
      postoperatively was minimal. CONCLUSIONS: The use of our multimodal analgesia
      regime is a well-tolerated and safe alternative to general or regional anesthesia
      for patients undergoing PCNL.

PMID- 19397429
TI  - Efficacy of peritubal local anesthetic infiltration in alleviating postoperative
      pain in percutaneous nephrolithotomy.
AB  - BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy (PCNL) is a safe and
      effective endourologic procedure in patients with renal calculi. It is less
      morbid than open surgery. However, the patient complains of pain around the
      nephrostomy tube and demands for good postoperative analgesia. Skin infiltration
      with bupivacaine around the nephrostomy tube is not effective, so we hypothesize
      that peritubal infiltration of bupivacaine from renal capsule to the skin along
      the nephrostomy tract may alleviate postoperative pain. PATIENTS AND METHODS: A
      randomized controlled study was designed in 40 American Society of
      Anesthesiologists (ASA) grade I patients to assess the impact of peritubal
      bupivacaine infiltration with 23-gauge spinal needle along the nephrostomy tract
      after PCNL under fluoroscopic guidance. Patients were randomized to receive 20 mL
      of 0.25% bupivacaine in block group (n = 20) or no infiltration in control group
      (n = 20) at the conclusion of the procedure. Postoperative pain score and
      analgesic requirement for the first 24 hours were assessed by visual and dynamic
      visual analog scales second hourly. Rescue analgesia with injection tramadol Hcl
      50-100 mg was given intravenously to a maximum total dose of 400 mg when pain
      score exceeded 4. RESULTS: Pain scores and analgesic requirement for the first 24
      hours postoperatively were significantly lesser in the block group than in the
      control group of patients at all points of time and were statistically
      significant (p < 0.005). CONCLUSION: In this study a significant difference in
      the pain scores and analgesic requirement was noted in the two groups of
      patients. Peritubal infiltration of 0.25% bupivacaine solution is efficient in
      alleviating postoperative pain after PCNL.

PMID- 19397430
TI  - Intraurethral lubricants: a critical literature review and recommendations.
AB  - In current clinical practice, lidocaine gel is widely used as a local anesthetic
      lubricant before various forms of transurethral instrumentation. Over the past
      few years, the value of local anesthesia during urethral catheterization and
      flexible or rigid cystoscopy has been questioned. Strong data are lacking, and
      the results from the different studies are contradictory. As a result, the
      correct use of the intraurethral gels is, for the most part, left to individual
      preference. The purpose of this review is to provide an overview of the
      characteristics of the intraurethral gels, to assess the effectiveness, and to
      define evidence-based indications for their use.

PMID- 19397431
TI  - Laparoendoscopic single-site nephrectomy using a homemade single-port device for
      single-system ectopic ureter in a child: initial case report.
AB  - A 3-year-old girl with a history of continuous urinary incontinence was found to
      have a right single-system ectopic ureter. She underwent laparoendoscopic single
      site nephrectomy without any intraoperative or postoperative complications. To
      the best of our knowledge, this is the first case report of a laparoendoscopic
      single-site nephrectomy for single-system ectopic ureter in a child.

PMID- 19397432
TI  - Gay identity-related factors and sexual risk among men who have sex with men in
      San Francisco.
AB  - This study explored the relationship between gay identity-related factors (gay
      community involvement, gay bar attendance, gay identity importance, and self
      homophobia) and unprotected anal sex (UA) in the past 3 months among men who have
      sex with men (MSM) of three different race/ethnicity groups. Four hundred eighty
      three MSM (mean age 34) were recruited in the San Francisco Bay Area (33% African
      American, 34% Latino and 33% White). Compared with White MSM, African American
      and Latino MSM were less likely to identify as gay, and to attend gay bars/clubs,
      and more likely to report self-homophobia. Just over one third of the sample
      reported UA (did not vary by race). Gay community involvement was associated with
      receptive UA with all partners (adjusted odds ratio [AOR = 1.30, 95% Confidence
      Interval (CI) = 1.06-1.60). Gay bar attendance was associated with insertive UA
      with all partners (AOR = 1.20, 95% CI = 1.01-1.43) and with HIV-discordant
      partners (AOR = 1.35, 95% CI = 1.08-1.69). Implications for prevention include
      addressing community norms and encouraging alternatives to bars as settings in
      which to meet and socialize with other MSM.

PMID- 19397433
TI  - A longitudinal quality-of-life study of HIV-infected persons in South India: the
      case for comprehensive clinical care and support services.
AB  - This study longitudinally assesses the quality of life (QOL) of HIV-infected
      individuals in a resource-limited setting prior to the extensive generic roll-out
      of highly active antiretroviral therapy. Data was collected on 136 individuals
      receiving clinical care at Y.R. Gaitonde Centre for AIDS Research and Education
      YRG CARE, a large community-based HIV tertiary care referral center in Chennai,
      South India. The QOL questionnaire was administered to participants at baseline,
      6-months follow-up, and 12-month follow-up, and analysis of variance was used to
      assess for significant differences in mean QOL scores for each of these visits.
      Study findings showed that QOL scores significantly improved in all five domains
      of the questionnaire between participants' baseline visit, second interview, and
      third interviews (p < 0.01). We conclude that a multidisciplinary approach to
      managing HIV infection can enhance patients' QOL, independent of antiretroviral
      therapy.

PMID- 19397434
TI  - Informing interventions: the importance of contextual factors in the prediction
      of sexual risk behaviors among transgender women.
AB  - This study identifies contextual factors that predict risky sexual behavior among
      153 transgender women who participated in a structured survey soliciting
      information on demographics, substance use, HIV status, risk behaviors, and other
      health and psychosocial factors. Multivariate logistic regression models were
      used to determine predictors. Inconsistent condom use was associated with
      stimulant use, unstable housing, and recruitment site. Substance use during sex
      was associated with unstable housing and stimulant use. Sex work was associated
      with hormone use, gender confirming surgeries, and younger age. When developing
      interventions for transgender women, it may be useful to focus on predictors of
      risk behavior rather than predictors of current HIV status (i.e., race/ethnicity
      as "risk factor"), because these behaviors are the target of interventions aimed
      at sexual risk reduction. Implications include potential benefits of context
      specific interventions, structural interventions addressing barriers to housing
      and health care, and culturally specific substance abuse treatment programs for
      transgender women.

PMID- 19397435
TI  - Replicating an intervention: the tension between fidelity and adaptation.
AB  - Increased awareness of the importance of tailoring interventions to participants'
      cultures has focused attention on the limited generalizability of a single test
      of an intervention to determine efficacy. Adaptation is often necessary to
      replicate interventions across cultures. This produces a tension between fidelity
      to the original intervention and adaptations necessary to make the intervention
      relevant to the culture and circumstances of participants. This article discusses
      issues that arise during the course of replication, with illustrations from a
      replication to test the efficacy of an HIV prevention intervention for youth,
      using a randomized controlled design. Analysis of the issues raised leads us to
      suggest that a "science of replication" needs to be developed.

PMID- 19397437
TI  - Assessing motivations to engage in intentional condomless anal intercourse in HIV
      risk contexts ("Bareback Sex") among men who have sex with men.
AB  - Although condom use is an effective barrier against HIV transmission, some men
      who have sex with men (MSM) engage in bareback sex (unprotected anal sex in risky
      contexts) and increase their risk for HIV (re)infection. Understanding MSM's
      decision to bareback (vis-a-vis condom use) is essential to develop effective
      HIV/AIDS prevention programs for this population. An ethnically diverse sample of
      men who bareback (n = 120) was recruited exclusively on the Internet and
      stratified to include two thirds who reported both unprotected receptive anal
      intercourse (URAI) and being HIV uninfected. We used exploratory factor analysis
      to explore the domains within the Decisional Balance to Bareback (DBB) scale, and
      test the association between DBB and risky sexual behaviors. HIV-positive MSM (n
      = 31) reported higher costs/losses associated with condom use than HIV-negative
      men (n = 89). We found two underlying factors in the DBB scale: a Coping with
      Social Vulnerabilities subscale (eight items; alpha = .89) and a Pleasure and
      Emotional Connection subscale (five items; alpha = .92). We found a positive
      association between DBB (i.e. greater gains associated with bareback sex) and
      URAI occasions, number of partners, and having one or more sero-discordant
      partners in the past 3 months. We conclude that because MSM may avoid using
      condoms in order to cope with psychosocial vulnerabilities and create intimacy
      with other MSM, this population could benefit from alternatives to condoms such
      as pre/post exposure prophylaxis and rectal microbicides.

PMID- 19397438
TI  - "If you don't abstain, you will die of AIDS": AIDS education in Kenyan public
      schools.
AB  - We explored constraints of implementing AIDS education in public schools in
      Kenya. Sixty interviews with teachers and 60 focus group discussions with
      students were conducted in 21 primary and nine secondary schools. System/school
      level constraints included lack of time in the curriculum, limited reach of
      secondary-school students (because AIDS education is embedded in biology, which
      is not compulsory), and disapproval of openness about sex and condoms by the
      Ministry of Education and parents. Alternative strategies to teach about AIDS had
      their own constraints. Teachers lacked training and support and felt
      uncomfortable with the topic. They were not used to interactive teaching methods
      and sometimes breached confidentiality. Teachers' negative attitudes constrained
      students from seeking information. Training interventions should be provided to
      teachers to increase their self-confidence, foster more positive attitudes, and
      stimulate interactive teaching methods. The Ministry of Education needs to have a
      clear policy toward the promotion of condoms.

PMID- 19397436
TI  - Evaluating nurses' implementation of an infant-feeding counseling protocol for
      HIV-infected mothers: The Ban Study in Lilongwe, Malawi.
AB  - A process evaluation of nurses' implementation of an infant-feeding counseling
      protocol was conducted for the Breastfeeding, Antiretroviral and Nutrition (BAN)
      Study, a prevention of mother-to-child transmission of HIV clinical trial in
      Lilongwe, Malawi. Six trained nurses counseled HIV-infected mothers to
      exclusively breastfeed for 24 weeks postpartum and to stop breastfeeding within
      an additional four weeks. Implementation data were collected via direct
      observations of 123 infant feeding counseling sessions (30 antenatal and 93
      postnatal) and interviews with each nurse. Analysis included calculating a
      percent adherence to checklists and conducting a content analysis for the
      observation and interview data. Nurses were implementing the protocol at an
      average adherence level of 90% or above. Although not detailed in the protocol,
      nurses appropriately counseled mothers on their actual or intended formula milk
      usage after weaning. Results indicate that nurses implemented the protocol as
      designed. Results will help to interpret the BAN Study's outcomes.

PMID- 19397439
TI  - Suppression of NF-kappaB activity by parthenolide induces X-ray sensitivity
      through inhibition of split-dose repair in TP53 null prostate cancer cells.
AB  - We have shown that parthenolide, a sesquiterpene lactone, is a radiation
      sensitizer for human CGL1 hybrid cells that have constitutively activated NF
      kappaB and wild-type p53. Since many malignant cells have nonfunctional p53, we
      investigated whether parthenolide could alter the X-ray sensitivity of PC-3
      prostate cancer cells, a p53 null cell line with constitutively activated NF
      kappaB. The addition of 5 microM parthenolide induced non-apoptotic cell death,
      inhibited PC-3 proliferation, and increased the population doubling time from
      23+/-1 h to 49+/-4 h. Parthenolide also inhibited constitutive and radiation
      induced NF-kappaB binding activity and enhanced the X-ray sensitivity of these
      p53 null PC-3 cells by a dose modification factor of 1.7. Cell cycle analysis of
      PC-3 cells treated with parthenolide showed only small alterations in G1 and G2/M
      cells, and these appeared to be insufficient to explain the observed
      radiosensitization. Split-dose studies using clinically relevant 2- and 4-Gy
      fractions demonstrated that parthenolide completely inhibited split-dose repair
      in PC-3 cells. We hypothesized that inhibition of NF-kappaB activity by
      parthenolide was responsible for the observed X-ray sensitization and inhibition
      of split-dose repair. To test this hypothesis, we knocked down the expression of
      NF-kappaB p65 protein, an active component of NF-kappaB in both PC-3 and CGL1
      cells, by siRNA. Inhibition of NF-kappaB activity by knockdown of p65 increased
      radiation sensitivity and completely inhibited split-dose repair in both cell
      lines in a nearly identical manner as parthenolide treatment alone. Treating p65
      depleted PC-3 cells with 5 microM parthenolide did not further increase their
      radiation sensitivity or the inhibition of split-dose repair. We propose that the
      suppression of radiation-induced NF-kappaB activity by parthenolide leads to X
      ray sensitization through inhibition of split-dose repair in p53 null PC-3
      prostate cancer cells.

PMID- 19397440
TI  - The complexity of double-strand break ends is a factor in the repair pathway
      choice.
AB  - The repair of double-strand breaks in mammalian cells is carried out by two
      pathways: homologous recombination and nonhomologous end joining. The factors
      that regulate the mechanism through which a specific repair pathway is activated
      are still not clearly defined. To study whether the complexity of the double
      strand break ends is a factor that determines the choice of the repair pathway,
      we examined the involvement of homologous recombination by the formation of Rad51
      foci in human HeLa cells treated with bleomycin and ionizing radiation. The
      quantity of double-strand breaks was determined by gel electrophoresis and the
      formation of gamma-H2AX foci. Two hours after treatment with low doses of the
      agents that induced similar quantities of double-strand breaks that could be
      repaired effectively by the cells, Rad51 foci were observed only in the
      irradiated cells. Rad51 foci appeared in bleomycin-treated cells after prolonged
      exposure to the drug when the cells were arrested in the G2 phase of the cell
      cycle. Since bleomycin produces double-strand breaks that are less complex than
      the breaks induced by ionizing radiation, these results indicate that the
      complexity of the break ends is a factor in the choice of repair pathway and that
      homologous recombination is recruited in the repair of breaks with more complex
      multiply damaged ends during the late S and G2 phases of the cell cycle.

PMID- 19397441
TI  - Positional stability of damaged chromatin domains along radiation tracks in
      mammalian cells.
AB  - Irradiation of cell nuclei with charged particles leads to the spatially defined
      production of DNA damage along the particle trajectories, thus facilitating
      studies on the dynamics of radiation-induced protein foci associated with lesion
      processing. Here we used visual inspection and computational analysis of the
      track morphology after immunodetection to describe the patterns of formation of
      gamma-H2AX foci and the repair-related proteins 53BP1 and RPA. We addressed the
      influence of lesion density on gamma-H2AX formation and the mobility of damaged
      chromatin sites by using low-angle irradiation of cell monolayers with low-energy
      carbon or uranium ions. We show the discrete formation of gamma-H2AX foci and the
      recruitment of repair-related proteins along ion trajectories over an LET range
      from 200 to 14300 keV/microm in human fibroblasts and in HeLa cells. The marked
      DSBs exhibited a limited mobility that was independent of the LET. The moderate
      extent of mobility in human fibroblasts pointed to a relatively stable
      positioning of the damaged chromatin domains during repair, in contrast to HeLa
      cells, which showed significant changes in the streak patterns in a fraction of
      cells, suggesting greater mobility in the local processing of DSBs. Our data
      indicate that the presence of single or multiple DSBs is not associated with an
      altered potential for movement of damaged chromatin. We infer that the repair of
      high-LET radiation-induced DSBs in mammalian cells is not coupled to an increased
      motional activity of lesions enhancing the probability of translocations.

PMID- 19397442
TI  - Forskolin decreases phosphorylation of histone H2AX in human cells induced by
      ionizing radiation.
AB  - Forskolin is a natural compound found in the coleus herb that activates the
      enzyme adenylate cyclase and increases the concentration of intracellular cyclic
      AMP (cAMP). This chemical is widely used as a stimulating food additive. It is
      unknown whether forskolin can effect cellular responses to ionizing radiation,
      such as induction of phosphorylation of histone H2AX (gamma-H2AX) in megabase
      chromatin domains near DNA double-strand breaks (DSBs). Here we report that
      treatment with forskolin decreases H2AX phosphorylation after irradiation
      detected by immunoblotting or by analysis of the overall gamma-H2AX-associated
      fluorescence in the nuclei. However, this chemical does not affect the number of
      gamma-H2AX foci, the frequency of radiation-induced chromosome aberrations, or
      cell survival after X irradiation, which is consistent with the view that it does
      not change the induction of repair of DSBs. We suggest that the overall decrease
      of H2AX phosphorylation after treatment with forskolin in irradiated cells
      reflects a lesser extent of apparent H2AX modification at individual DSBs that
      may be caused by inhibition of the initial spread of gamma-H2AX and/or by
      stimulation of elimination of gamma-H2AX from chromatin after DSB rejoining.

PMID- 19397443
TI  - Persistence of radiation-induced chromosome aberrations in a long-term cell
      culture.
AB  - The aim of the present study was to evaluate the persistence of chromosome
      aberrations induced by X rays. FISH painting and mFISH techniques were applied to
      long-term cultures of irradiated cells. With painting, at 2 Gy the frequency of
      apparently simple translocations remained almost invariable during all the
      culture, whereas at 4 Gy a rapid decline was observed between the first and the
      second samples, followed by a slight decrease until the end of the culture.
      Apparently simple dicentrics and complex aberrations disappeared after the first
      sample at 2 and 4 Gy. By mFISH, at 2 Gy the frequency of complete plus one-way
      translocations remained invariable between the first and last sample, but at 4 Gy
      a 60% decline was observed. True incomplete simple translocations disappeared at
      2 and 4 Gy, indicating that incompleteness could be a factor to consider when the
      persistence of translocations is analyzed. The analysis by mFISH showed that the
      frequency of complex aberrations and their complexity increased with dose and
      tended to disappear in the last sample. Our results indicate that the influence
      of dose on the decrease in the frequency of simple translocations with time
      postirradiation cannot be fully explained by the disappearance of true incomplete
      translocations and complex aberrations. The chromosome involvement was random for
      radiation-induced exchange aberrations and non-random for total aberrations.
      Chromosome 7 showed the highest deviations from expected, being less and more
      involved than expected in the first and last samples, respectively. Some
      preferential chromosome-chromosome associations were observed, including a
      coincidence with a cluster from radiogenic chromosome aberrations described in
      other studies.

PMID- 19397444
TI  - DNA fragmentation induced in human fibroblasts by 56Fe ions: experimental data
      and Monte Carlo simulations.
AB  - We studied the DNA fragmentation induced in human fibroblasts by iron-ion beams
      of two different energies: 115 MeV/nucleon and 414 MeV/nucleon. Experimental data
      were obtained in the fragment size range 1-5700 kbp; Monte Carlo simulations were
      performed with the PARTRAC code; data analysis was also performed through the
      Generalized Broken Stick (GBS) model. The comparison between experimental and
      simulated data for the number of fragments produced in two different size ranges,
      1-23 kbp and 23-5700 kbp, gives a satisfactory agreement for both radiation
      qualities. The Monte Carlo simulations also allow the counting of fragments
      outside the experimental range: The number of fragments smaller than 1 kbp is
      large for both beams, although with a strong difference between the two cases. As
      a consequence, we can compute different RBEs depending on the size range
      considered for the fragment counting. The PARTRAC evaluation takes into account
      fragments of all sizes, while the evaluation from the experimental data considers
      only the fragments in the range of 1-5700 kbp. When the PARTRAC evaluation is
      restricted to this range, the agreement between experimental and computed RBE
      values is again good. When fragments smaller than 1 kbp are also considered, the
      RBE increases considerably, since gamma rays produce a small number of such
      fragments. The analysis performed with the GBS model proved to be quite sensitive
      to showing, with a phenomenological single parameter, variations in double-strand
      break (DSB) correlation.

PMID- 19397445
TI  - Cadmium-induced adaptive response in cells of Chinese hamster ovary cell lines
      with varying DNA repair capacity.
AB  - The combined exposure to environmental toxicants such as heavy metals and
      radiation is an important research area in health protection. The aim of this
      study was to investigate the role of DNA repair and the phosphatidylinositol 3
      kinase (PI3K) family in the cadmium-induced adaptive response to toxicants or
      radiation. Using cells of three Chinese hamster ovary (CHO) cell lines with
      different capacities to repair DNA damage, we found that pre-exposure to cadmium
      at a nonlethal concentration could induce an adaptive response to a subsequent
      challenge with cadmium or radiation in all the cell lines. The magnitude of the
      adaptive response in adapted cells was dependent on several factors, including
      DNA repair capacity, the priming dose of cadmium, and the challenging dose of
      cadmium or radiation. When the cells were challenged with 50 microM CdCl2, the
      adaptive response was less evident in XRCC1-defective EM-C11 cells than in cells
      of the other two cell lines. Moreover, treatment of cells with wortmannin or KU
      55933 eliminated the adaptive response in all the cell lines. Our data suggest
      that the triggering of a cadmium-induced adaptive response was independent of DNA
      repair capacity. Single-strand break (SSB) repair or base excision repair (BER)
      rather than double-strand break (DSB) repair was mainly involved in the adaptive
      response. This response of cells to a further challenge with cadmium or radiation
      may be mediated through the ataxia telangiectasia mutated (ATM) pathway.

PMID- 19397447
TI  - Gene expression and enzyme activity of mitochondrial proteins in irradiated
      rainbow trout (Oncorhynchus mykiss, Walbaum) tissues in vitro.
AB  - In recent years ethical, legislative and economic pressures have created a
      renewed interest in the development of alternatives to in vivo animal
      experiments. In vitro studies, particularly those using cell cultures, have been
      used increasingly as tools to assess the degree of toxicity associated with or
      present in particular environments. While cell cultures are useful to give
      relative toxicity values, genotypic and phenotypic integrity may be compromised
      in the continuous artificial environment they experience. In addition, cell
      cultures lack the complexity of functional organs and thus do not truly represent
      the effects that toxins exert on organ and organism functionality. In this study,
      ex vivo tissue cultures of rainbow trout gill, skin and spleen samples were
      analyzed for variation of expression in genes associated with oxidative
      phosphorylation after exposure to ionizing radiation. Significant radiation
      induced changes in gene expression and enzyme activity associated with the
      mitochondrial oxidative phosphorylation process were identified. The tissues
      examined in this study demonstrated an exposure threshold at which radiation dose
      stimulates an alteration in the regulatory activity of mitochondrial-associated
      genes. Spleen tissues exposed to low levels of radiation (0.1 Gy) appeared most
      sensitive whereas skin tissues proved least sensitive, reacting only to higher
      doses (>1 Gy). We propose this investigative approach as an innovative
      alternative to in vivo studies because it identifies toxic exposure in vitro and
      could significantly reduce the number of live-animal toxicity tests required.

PMID- 19397446
TI  - Ionizing radiation induces microhomology-mediated end joining in trans in yeast
      and mammalian cells.
AB  - DNA double-strand breaks repaired through nonhomologous end joining require no
      extended sequence homology as a template for the repair. A subset of end-joining
      events, termed microhomology-mediated end joining, occur between a few base pairs
      of homology, and such pathways have been implicated in different human cancers
      and genetic diseases. Here we investigated the effect of exposure of yeast and
      mammalian cells to ionizing radiation on the frequency and mechanism of rejoining
      of transfected unirradiated linear plasmid DNA. Cells were exposed to gamma
      radiation prior to plasmid transfection; subsequently the rejoined plasmids were
      recovered and the junction sequences were analyzed. In irradiated yeast cells,
      68% of recovered plasmids contained microhomologies, compared to only 30% from
      unirradiated cells. Among them 57% of events used>or=4 bp of microhomology
      compared to only 11% from unirradiated cells. In irradiated mammalian cells, 54%
      of plasmids used>or=4 bp of microhomology compared to none from unirradiated
      cells. We conclude that exposure of yeast and mammalian cells to radiation prior
      to plasmid transfection enhances the frequency of microhomology-mediated end
      joining events in trans. If such events occur within genomic locations, they may
      be involved in the generation of large deletions and other chromosomal
      aberrations that occur in cancer cells.

PMID- 19397448
TI  - Radiation leukemogenesis in mice: loss of PU.1 on chromosome 2 in CBA and C57BL/6
      mice after irradiation with 1 GeV/nucleon 56Fe ions, X rays or gamma rays. Part
      I. Experimental observations.
AB  - Since deletion of the PU.1 gene on chromosome 2 is a crucial acute myeloid
      leukemia (AML) initiating step in the mouse model, we quantified PU.1 deleted
      cells in the bone marrow of gamma-, X- and 56Fe-ion-irradiated mice at various
      times postirradiation. Although 56Fe ions were initially some two to three times
      more effective than X or gamma rays in inducing PU.1 deletions, by 1 month
      postirradiation, the proportions of cells with PU.1 deletions were similar for
      the HZE particles and the sparsely ionizing radiations. These results indicate
      that while 56Fe ions are more effective in inducing PU.1 deletions, they are also
      more effective in causing collateral damage that removes hit cells from the bone
      marrow. After X, gamma or 56Fe-ion irradiation, AML-resistant C57BL/6 mice have
      fewer cells with PU.1 deletions than CBA mice, and those cells do not persist in
      the bone marrow of the C57B6/6 mice. Our findings suggest that quantification of
      PU.1 deleted bone marrow cells 1 month postirradiation can be used as surrogate
      for the incidence of radiation-induced AML measured in large-scale mouse studies.
      If so, PU.1 loss could be used to systematically assess the potential
      leukemogenic effects of other ions and energies in the space radiation
      environment.

PMID- 19397449
TI  - Radiation leukemogenesis in mice: loss of PU.1 on chromosome 2 in CBA and C57BL/6
      mice after irradiation with 1 GeV/nucleon 56Fe ions, X rays or gamma Rays. Part
      II. Theoretical considerations based on microdosimetry and the initial induction
      of chromosome aberrations.
AB  - Chromosome aberrations in mitotic bone marrow cells of CBA/Ca and C57BL/6 mice
      were measured 1 day after exposure to 1 Gy of 1 GeV/nucleon 56Fe ions or 3 Gy of
      gamma rays. The proportion that have lost a region of chromosome 2 containing the
      PU.1 gene could be explained by a model based on these measurements. The
      distribution of aberrations among cells was close to the expected Poisson for the
      gamma-irradiated cells, but for the HZE 56Fe ions the distribution was highly
      dispersed. The observations were consistent with the results of an analysis
      similar to that of Edwards and co-workers in 1980 after ex vivo irradiation of
      human blood with alpha particles. The analysis used to fit the current data was
      based on a compound Poisson process, also used previously by others, but in
      addition included the random nature of parameters involved such as cell nuclear
      diameter, particle traversal lengths through cell nuclei, production of
      aberrations, and cell cycle arrest per traversal. From the measured numbers of
      acentric fragments produced, the relative size of chromosome 2 and the region
      associated with PU.1 deletions, an independent prediction of PU.1 loss agreed
      well with measurements described in the accompanying paper.

PMID- 19397450
TI  - Long incubation period for the induction of cancer by thorotrast is attributed to
      the uneven irradiation of liver cells at the microscopic level.
AB  - Irradiation from internally deposited radionuclides induces malignant tumors.
      Ingested long-lived radionuclides accumulate in specific organs that are
      irradiated throughout life. To elucidate why the development of malignant tumors
      requires long-term internal exposure, of the order of decades, despite the fact
      that irradiation is continuous over this period, we analyzed intrahepatic
      cholangiocarcinoma in Thorotrast patients (Th-ICC). Autoradiography showed that
      the density of alpha-particle tracks was 50 times more concentrated than would be
      expected if Thorotrast were evenly distributed throughout the liver. The age
      incidence curves revealed that while the incidence of hepatobiliary cancer in
      Japan increased in proportion to the 7th power of age, that of Th-ICC increased
      to the 6th power. Internal radiation significantly increased the randomness of
      hepatocyte distribution but not the density. Three major factors are considered
      to be responsible for the long incubation time: the uneven distribution of
      radionuclides, the limited range of radiation, and the movement of tumor
      precursor cells. Target cells susceptible to malignant transformation may undergo
      one event and may then migrate outside of the range of alpha particles, thereby
      avoiding immediate induction of successive additional events that would lead to
      cell death or neoplastic changes.

PMID- 19397451
TI  - A cohort study of childhood cancer incidence after postnatal diagnostic X-ray
      exposure.
AB  - Ionizing radiation is an established cause of cancer, yet little is known about
      the health effects of doses from diagnostic examinations in children. The risk of
      childhood cancer was studied in a cohort of 92.957 children who had been examined
      with diagnostic X rays in a large German hospital during 1976-2003. Radiation
      doses were reconstructed using the individual dose area product and other
      exposure parameters, together with conversion coefficients developed specifically
      for the medical devices and standards used at the radiology department. Newly
      diagnosed cancers occurring between 1980 and 2006 were determined through record
      linkage to the German Childhood Cancer Registry. The median radiation dose was 7
      microSv. Eight-seven incident cases were found in the cohort: 33 leukemia, 13
      lymphoma, 10 central nervous system tumors, and 31 other tumors. The standardized
      incidence ratio (SIR) for all cancers was 0.99 (95% CI: 0.79-1.22). No trend in
      the incidence of total cancer, leukemia or solid tumors with increasing radiation
      dose was observed in the SIR analysis or in the multivariate Poisson regression.
      Risk did not differ significantly in girls and boys. Overall, while no increase
      in cancer risk with diagnostic radiation was observed, the results are compatible
      with a broad range of risk estimates.

PMID- 19397457
TI  - Multiplexed staining of live human embryonic stem cells for flow cytometric
      analysis of pluripotency markers.
AB  - Use of flow cytometry to detect pluripotency markers on or in human embryonic
      stem cells (hESCs) is a powerful analytical tool. However, current staining
      methodologies for high-content analysis of large numbers of samples utilize large
      quantities of primary and secondary antibodies, are time consuming, and may
      suffer from sample-to-sample variability. To circumvent these issues, we have
      developed a reproducible, quick, and cost-effective method of staining 12
      populations of hESCs grown under different conditions by labeling each with a
      unique optical signature (UOS). The UOS for each population is achieved by
      combining different combinations and concentrations of 3 esterase activated, live
      cell, fluorescent indicators. The individually stained populations are then
      combined and an aliquot of the hESC samples stained for pluripotency or other
      markers of interest in the far-red region of the spectrum. Based on the unique
      fluorescent intensity and emission wavelengths of each population, the
      characteristics of each population are decoded in software after flow cytometric
      analysis. We have validated both our staining procedure and decoding methods by
      mixing populations of differentiated and undifferentiated hESCs and successfully
      quantifying differences in the pluripotency markers SSEA-4, Tra-1-60, GCTM2, and
      CD9 between the 12 different populations. Our multiplexing approach allows for
      the addition of internal controls and reduces sample-to-sample variation, while
      offering a significant reduction in time and reagent consumption. We anticipate
      that this method will be of great benefit to laboratories conducting high-content
      flow cytometric analysis of hESCs.

PMID- 19397458
TI  - Accreditation: we want standards, not standardization.

PMID- 19397459
TI  - Electrocardiographic effects of lofexidine and methadone coadministration:
      secondary findings from a safety study.
AB  - STUDY OBJECTIVE: To determine the electrocardiographic effects of
      coadministration of lofexidine and methadone. DESIGN: Prospective, double-blind
      study. SETTING: Outpatient drug treatment research clinic. PARTICIPANTS: Fourteen
      adults (mean +/- SD age 34.9 +/- 5.3 yrs) with physical dependence on opioids.
      INTERVENTION: Participants were stabilized on methadone maintenance therapy,
      reaching a target dose of 80 mg/day. After 3 weeks of methadone stabilization,
      participants received lofexidine 0.4 mg or placebo once/day, each for 1 week,
      administered at the same time as methadone. From weeks 3-8, all subjects received
      lofexidine, with the dose escalated each week in 0.2-mg increments so that by
      week 8, participants were receiving lofexidine 1.6 mg/day. Electrocardiograms
      (ECGs) were obtained at baseline (before methadone), after stabilization with
      methadone, and after lofexidine coadministration during peak plasma lofexidine
      levels. MEASUREMENTS AND MAIN RESULTS: Prespecified outcome measures of mean and
      maximal changes in heart rate, and PR, QRS, and QTc intervals were obtained after
      stabilization with methadone and after lofexidine 0.4 mg coadministration.
      Repeated-measures regression showed no significant changes in heart rate or PR,
      QRS, or QTc interval after methadone stabilization, but a significant decrease in
      heart rate (mean +/- SD -8.0 +/- 7.3 beats/min, p=0.0006) after starting
      lofexidine. When data were analyzed by using maximal ECG response, again, no
      significant changes were noted during methadone induction compared with baseline,
      but significant changes did occur in all four ECG parameters when lofexidine was
      coadministered: decreased heart rate (mean +/- SD -9.6 +/- 5.8 beats/min,
      p<0.0001) and increased PR interval (+11.1 +/- 19.8 msec, p=0.026), QRS interval
      (+3.7 +/- 4.3 msec, p=0.002), and QTc interval (+21.9 +/- 40.8 msec, p=0.018). In
      three female participants, the change in QTc interval from baseline was
      clinically significant (> 40 msec). CONCLUSION: Our preliminary data suggest that
      coadministration of lofexidine and methadone induces QTc interval prolongation.
      This drug combination should be prescribed cautiously, with ECG monitoring.
      Furthermore, because the participants with the largest changes in QTc interval in
      our study were female, women may be at highest risk.

PMID- 19397460
TI  - Therapeutic drug monitoring of antimycobacterial drugs in patients with both
      tuberculosis and advanced human immunodeficiency virus infection.
AB  - STUDY OBJECTIVE: To determine the feasibility of therapeutic drug monitoring for
      adjusting low serum antimycobacterial concentrations in patients with both
      tuberculosis and advanced human immunodeficiency virus (HIV). DESIGN:
      Retrospective cohort study. DATA SOURCE: De-identified dataset from a
      tuberculosis clinic. PATIENTS: Twenty-one patients (median age 38 yrs, range 25
      68 yrs) with advanced HIV infection (CD4(+) cell count < 100 cells/mm(3)) who
      received treatment for active tuberculosis between March 2002 and September 2007.
      MEASUREMENTS AND MAIN RESULTS: We evaluated data based on the practices performed
      at the tuberculosis clinic. After the daily doses of isoniazid and rifamycins
      (rifampin or rifabutin) were ingested, serum concentrations were obtained at 2
      hours for isoniazid and rifampin, at 3 hours for rifabutin, and, when possible,
      at 6 hours for all three drugs to detect delayed absorption. Antimycobacterial
      drug concentrations were compared with published reference levels, and dosages
      were adjusted to achieve desired concentrations. Costs of monitoring were
      recorded for all patients. Of the 21 patients, 18 (86%) had low serum
      concentrations of at least one drug 2 hours after ingestion: 2 (10%) had low
      isoniazid concentrations, 5 (24%) had low rifamycin concentrations, and 11 (52%)
      had low serum concentrations of both drugs. The median number of dosage
      adjustments to attain normal concentrations was 1 (range 0-4 adjustments). The
      median cost/patient for therapeutic drug monitoring was $619 (range $230-1948).
      The median final doses to achieve normal concentrations were isoniazid 600 mg/day
      (range 300-1500 mg/day), rifampin 1050 mg/day (range 600-1200 mg/day), and
      rifabutin 300 mg (range 150-450 mg) 3 times/week. No patient demonstrated any
      adverse effects attributed to these higher doses. CONCLUSION: Low serum
      concentrations of antituberculous drugs, which suggest malabsorption, are common
      among patients with advanced HIV who also have tuberculosis but can be overcome
      with higher doses. Therapeutic drug monitoring may be an effective tool to
      optimize therapy, but needs further study.

PMID- 19397461
TI  - Ceftobiprole: first cephalosporin with activity against methicillin-resistant
      Staphylococcus aureus.
AB  - Ceftobiprole medocaril is the first member of a new series of advanced
      cephalosporins with activity against methicillin-resistant Staphylococcus aureus
      (MRSA). The drug received an approvable letter from the United States Food and
      Drug Administration (FDA) in March 2008 and from Health Canada in June 2008 for
      the treatment of complicated skin and skin structure infections including
      diabetic foot infections. Ceftobiprole exerts its antibacterial activity by
      inhibiting the penicillin-binding proteins (PBPs) involved in cell wall
      synthesis. It has an established stability against hydrolysis by many gram
      positive beta-lactamases and a higher affinity for various PBPs (such as PBP2a of
      MRSA or PBP2x of Streptococcus pneumoniae), which leads to a wider spectrum of
      activity compared with older beta-lactams. Ceftobiprole activity does not cover
      extended-spectrum beta-lactamase-producing Enterobacteriaceae and some other
      pathogens, including Enterococcus faecium or Acinetobacter baumanii. Generally
      well tolerated, with nausea and taste disturbance being the most common adverse
      events, ceftobiprole appeared noninferior to empiric therapy in several clinical
      trials. Ceftobiprole is available only for intravenous administration;
      recommended dosage regimens have not been approved by the FDA as of this writing.
      However, based on the Canadian package insert, expected dosage recommendations
      are 500 mg as a 1-hour intravenous infusion every 12 hours for the treatment of
      complicated skin and skin structure infections caused by certain gram-positive
      pathogens, and 500 mg as a 2-hour infusion every 8 hours when susceptible gram
      negative or both gram-positive and susceptible gram-negative pathogens are
      involved. Dosage adjustments are indicated for patients with moderate or severe
      renal impairment, and dosage recommendations are expected to be 500 or 250 mg,
      respectively, as a 2-hour infusion every 12 hours. Several precautions regarding
      hypersensitivity and drug incompatibility are reported. Ceftobiprole represents a
      promising option for the treatment of mono- and polymicrobial infections caused
      by multidrug-resistant gram-positive and susceptible gram-negative pathogens, but
      further toxicity and safety studies are warranted.

PMID- 19397462
TI  - Pharmacologic therapy for intermittent claudication.
AB  - Peripheral artery disease, defined as atherosclerosis in the lower extremities,
      affects nearly 8.5 million people in the United States. Due to the frequent
      asymptomatic manifestation of peripheral artery disease, diagnosis may be delayed
      and its true incidence underestimated. However, some patients may experience
      aching pain, numbness, weakness, or fatigue, a condition termed intermittent
      claudication. Peripheral atherosclerosis is associated with cardiovascular risk
      and physical impairment; therefore, treatment goals are aimed at decreasing
      cardiovascular risk, as well as improving quality of life. Little debate exists
      regarding the management of cardiovascular risk reduction, which consists of both
      antiplatelet therapy and risk factor modification. Despite recently published
      guidelines, the treatment of intermittent claudication is less well established
      and the management remains controversial and uncertain. Exercise remains the
      first-line therapy for intermittent claudication; however, pharmacologic
      treatment is often necessary. Although only two prescription drugs have been
      approved by the U.S. Food and Drug Administration for the treatment of
      intermittent claudication, several supplements and investigational agents have
      been evaluated. Therapeutic optimization should balance the anticipated
      improvements in quality of life with the potential safety risks.

PMID- 19397463
TI  - Comparison of sevelamer hydrochloride and sevelamer carbonate: risk of metabolic
      acidosis and clinical implications.
AB  - Hyperphosphatemia is highly prevalent in patients with chronic kidney disease
      (CKD), particularly in those with advanced or end-stage renal disease. Sevelamer
      hydrochloride is an ion-exchange resin that reduces serum phosphorus
      concentrations. The agent also produces favorable lipid profile effects and does
      not cause hypercalcemia. However, reported drawbacks of this agent are metabolic
      acidosis, high pill burden, and a relatively low affinity and selectivity for
      phosphate anions. Sevelamer carbonate is a new buffered formulation that does not
      increase the risk of metabolic acidosis. To determine the roles of these two
      agents in the treatment of hyperphosphatemia in patients with CKD, we performed a
      MEDLINE search (June 1995-June 2008) focusing on the mechanism of action of resin
      binding with phosphate and the development of metabolic acidosis. We also
      reviewed studies that evaluated the effects of sevelamer hydrochloride or
      sevelamer carbonate on serum bicarbonate concentrations. Several studies in
      patients with CKD and hyperphosphatemia who received hemodialysis or peritoneal
      dialysis found decreases in serum bicarbonate concentrations with the use of
      sevelamer hydrochloride, whereas sevelamer carbonate did not have this negative
      effect on bicarbonate concentrations. Both drugs appear to be equivalent in their
      abilities to lower serum phosphorus concentrations. However, as sevelamer
      carbonate does not decrease serum bicarbonate levels, it may be more appropriate
      for patients at risk for metabolic acidosis who require phosphate binders that do
      not contain calcium or aluminum.

PMID- 19397464
TI  - Antimicrobial dosing concepts and recommendations for critically ill adult
      patients receiving continuous renal replacement therapy or intermittent
      hemodialysis.
AB  - Infectious diseases and impaired renal function often occur in critically ill
      patients, and delaying the start of appropriate empiric antimicrobial therapy or
      starting inappropriate therapy has been associated with poor outcomes. Our
      primary objective was to critically review and discuss the influence of chronic
      kidney disease (CKD) and acute kidney injury (AKI) on the clinical
      pharmacokinetic and pharmacodynamic properties of antimicrobial agents. The
      effect of continuous renal replacement therapies (CRRTs) and intermittent
      hemodialysis (IHD) on drug disposition in these two populations was also
      evaluated. Finally, proposed dosing strategies for selected antimicrobials in
      critically ill adult patients as well as those receiving CRRT or IHD have been
      compiled. We conducted a PubMed search (January 1980-March 2008) to identify all
      English-language literature published in which dosing recommendations were
      proposed for antimicrobials commonly used in critically ill patients, including
      those receiving CRRT or IHD. All pertinent reviews, selected studies, and
      associated references were evaluated to ensure their relevance. Forty
      antimicrobial, antifungal, and antiviral agents commonly used in critically ill
      patients were included for review. Dosage recommendations were synthesized from
      the 42 reviewed articles and peer-reviewed, evidence-based clinical drug
      databases to generate initial guidance for the determination of antimicrobial
      dosing strategies for critically ill adults. Because of the evolving process of
      critical illness, whether in patients with AKI or in those with CKD, prospective
      adaptation of these initial dosing recommendations to meet the needs of each
      individual patient will often rely on prospectively collected clinical and
      laboratory data.

PMID- 19397465
TI  - Treatment of head and neck cancers: issues for clinical pharmacists.
AB  - Head and neck cancers are a heterogeneous group of diseases involving the oral
      cavity, pharyngeal tube, and larynx. Given the drug therapy options available,
      clinical pharmacists can play an important role in the care of this patient
      population. They can recommend a regimen based on efficacy, toxicity, and patient
      specific factors; ensure that the prescribed regimen has been studied and
      reported in the literature; verify dosages; and monitor and counsel patients
      about adverse effects. Chemotherapy plus radiation (chemoradiation) is often the
      standard treatment for patients with stage III or nonmetastatic stage IV head and
      neck cancer. Cisplatin-based regimens are preferred, although carboplatin may be
      appropriate in some circumstances. Induction therapy with a docetaxel-based
      regimen is recommended for some patients; however, this therapy has been
      associated with a high frequency of grade 3 and 4 neutropenia and febrile
      neutropenia. Cetuximab, an epidermal growth factor receptor inhibitor, is the
      newest agent approved for treatment of head and neck cancer. Although evidence
      supports cetuximab combined with cisplatin versus cisplatin alone for patients
      with metastatic disease, the role of combination therapy is less clear in
      patients undergoing chemoradiation. Patients with head and neck cancer may
      experience swallowing difficulties or mouth pain, possibly interfering with drug
      administration and adherence; thus, pharmacists in all practice settings should
      be knowledgeable about different regimens and alternative routes of
      administration. Xerostomia and mucositis are common adverse effects of radiation
      therapy, and it is critical that good oral hygiene practices are maintained.
      Patients may achieve symptomatic relief from xerostomia with saliva substitutes,
      and clinical experience suggests that use of pilocarpine is worthwhile. Until
      more evidence becomes available, prevention of xerostomia and mucositis with
      amifostine is still controversial. Salt-water rinses, bioadherent oral gel, and
      honey are relatively inexpensive and nontoxic agents for managing mucositis.
      Because of the expense of palifermin, it is best reserved for refractory cases.
      Skin toxicities are common with radiation. Rash is also a common adverse effect
      of cetuximab. When used together, they may produce complicated skin toxicities.
      It is important to become familiar with the grading of these rashes so that
      appropriate therapy can be recommended. As pharmacotherapy for head and neck
      cancers continues to evolve, clinical pharmacists will continue to have an
      important role in optimizing treatment for patients by balancing efficacy and
      toxicity.

PMID- 19397466
TI  - Insights from the Society of Infectious Diseases Pharmacists on antimicrobial
      stewardship guidelines from the Infectious Diseases Society of America and the
      Society for Healthcare Epidemiology of America.
AB  - In 2007, the Infectious Diseases Society of America and the Society for
      Healthcare Epidemiology of America published a document that addressed the major
      considerations for the justification, description, and conduct of antimicrobial
      stewardship programs. Our document is intended to continue the dialogue of these
      formalized programmatic strategies. We briefly review the guidelines, including
      the two primary strategies (prospective auditing with feedback, and
      preauthorization), and the supplemental strategies (education, information
      technology, transitional therapy, de-escalation or streamlining, and dose
      optimization). Discussions are introduced or furthered in the areas of program
      goals, barriers and solutions, and outcome measures. Definition and training of
      infectious diseases pharmacists are presented in detail. We offer keys to future
      success, which include continued collaboration and expanded use of information
      technology.

PMID- 19397467
TI  - Clopidogrel-induced hepatocellular injury and cholestatic jaundice in an elderly
      patient: case report and review of the literature.
AB  - In patients undergoing percutaneous coronary intervention and in those with acute
      coronary syndromes, clopidogrel plus aspirin is the first-line antiplatelet
      therapy for reducing cardiovascular events. Although clopidogrel is generally
      well tolerated, with rash, indigestion, vomiting, diarrhea, and bleeding being
      the most common adverse effects, rare but serious complications may occur. We
      describe a 78-year-old woman who underwent percutaneous coronary intervention
      with drug-eluting stents; clopidogrel and aspirin were started as antiplatelet
      therapy. Three weeks later, the patient developed mixed hepatocellular and
      cholestatic liver injury. Clopidogrel was discontinued, and her liver profile
      results began to improve. Her diagnostic work-up included screening for
      hepatitis, infectious mononucleosis, and rheumatologic diseases, as well as
      ultrasonography, magnetic resonance imaging, and endoscopic retrograde
      cholangiopancreaticography; all results were normal. On day 5 of hospitalization,
      because of the patient's risk for thrombosis secondary to the drug-eluting
      stents, clopidogrel was reintroduced; her liver enzyme levels increased. In the
      absence of any biliary obstruction or other obvious causes of hepatic injury,
      drug-induced hepatocellular injury and cholestatic jaundice were suspected, and
      clopidogrel was again discontinued. The patient's liver function tests gradually
      improved 3 days later and showed marked improvement at her 2-week follow-up visit
      after discharge. Use of the Maria and Victorino scale for diagnosis of drug
      induced hepatotoxicity indicated a probable (score of 14) relationship between
      clopidogrel and mixed hepatocellular injury and cholestatic jaundice in this
      patient. Although routine liver function testing is not recommended in patients
      who receive clopidogrel, having a high index of clinical suspicion, drug
      rechallenge, and excluding other obvious causes are required to establish the
      diagnosis of a rare drug complication such as clopidogrel-induced hepatic injury.

PMID- 19397468
TI  - Nephrogenic diabetes insipidus induced by two amphotericin B liposomal
      formulations.
AB  - Immunocompromised patients are at risk for invasive molds and resistant fungal
      infections for which amphotericin B may be the only feasible treatment.
      Nephrogenic diabetes insipidus (DI) and renal tubular acidosis are known adverse
      effects of conventional amphotericin B; however, nephrogenic DI has been
      uncommonly associated with liposomal amphotericin B formulations. We describe an
      18-year-old woman with aplastic anemia who developed invasive aspergillosis. She
      began treatment with high-dose (10 mg/kg/day) liposomal amphotericin B at home;
      however, her condition worsened, and she was hospitalized. Therapy with liposomal
      amphotericin B was continued until the patient began having symptoms consistent
      with nephrogenic DI. These symptoms resolved after discontinuation of liposomal
      amphotericin B; however, after rechallenge with lipid complex amphotericin B (5
      mg/kg/day), the symptoms returned. The patient's nephrogenic DI was successfully
      treated with diuretics. Use of the Naranjo adverse drug reaction probability
      scale score indicated a probable relationship between liposomal amphotericin B
      and the development of nephrogenic DI. To our knowledge, this is the third report
      of nephrogenic DI induced by liposomal amphotericin B. This adverse effect is one
      of many severe adverse effects caused by all formulations of amphotericin B. A
      clear understanding of these adverse effects is vital for the clinician to
      successfully weigh the risks and benefits of antifungal therapy.

PMID- 19397469
TI  - Long-term superior performance of a stem cell/hepatocyte device for the treatment
      of acute liver failure.
AB  - Cell-based technologies to support/restore organ function represent one of the
      most promising avenues in the treatment of acute liver failure (ALF). Recently,
      mesenchymal stem cells (MSCs) have been reported as a new therapeutic for
      inflammatory conditions. Here, we demonstrate the efficacy of MSCs, when
      cocultured with hepatocytes, to provide combination hepatic and antiinflammatory
      therapy in the setting of ALF. MSCs were shown to have multiple beneficial
      effects in vitro that were relevant in a therapeutic context, including (1)
      hepatocellular functional support, (2) secretion of molecules that inhibit
      hepatocyte apoptosis, and (3) modulation of an acute phase response by
      hepatocytes cultured in ALF-induced serum. In addition, we show that the MSC
      secretome is dynamically changed in response to serum exposure from ALF rats. We
      then conducted a therapeutic trial of liver assist devices (LADs). LADs
      containing cocultures of MSCs and hepatocytes provided a greater survival benefit
      compared to other coculture and monocellular control LADs. Treatment with MSC
      hepatocyte devices was associated with specific improvements in hepatic
      functional and histological parameters as well as decreasing inflammatory serum
      cytokine levels, validating a combined therapeutic effect. Moreover, MSC
      coculture reduced the overall cell mass of the device by an order of magnitude.
      These findings demonstrate the importance of nonparenchymal cells in the cellular
      composition of LADs, and strongly support the integration of MSCs into hepatocyte
      coculture-based LADs as a potential destination therapy for ALF.

PMID- 19397470
TI  - Fenestration defects in the rabbit jaw: an inadequate model for studying
      periodontal regeneration.
AB  - Periodontitis is an inflammatory disease affecting the support of the teeth,
      eventually leading to loosening and subsequent loss of teeth. Effective
      procedures for periodontal tissue engineering or regeneration require preclinical
      models before market introduction. Research has been performed in either small or
      large animals. Unfortunately, there is no intermediate-sized in vivo model
      available for periodontal regeneration studies, such as, for instance, rabbits.
      The objective of this study was to evaluate the rabbit as a new experimental
      model to study periodontal regeneration. In 12 rabbits, periodontal defects were
      created in a 4 x 6 mm bone window. The animals were sacrificed after 2, 4, 6, 8,
      10, and 12 weeks. Up to 6 weeks, the fenestration defects healed partly by repair
      and partly by regeneration. After 6 weeks the root had erupted to such an extent
      that the original root defect shifted into the oral cavity. This signifies that
      the periodontal ligament (PDL) bordering the original bone defect site is newly
      formed during the natural eruption process and not locally regenerated.
      Apparently, the new PDL originates from mesenchymal cells that arise from the
      apical part (sheath of Hertwig) and subsequently developed into PDL fibroblasts.
      At 12 weeks, no signs of surgery were present anymore. On the basis of our
      observation that the defect of the PDL was replaced rather than restored, we
      conclude that the rabbit model has disadvantages and is less suitable for studies
      of regeneration of PDL.

PMID- 19397471
TI  - The microenvironment of freeze-injured mouse urinary bladders enables successful
      tissue engineering.
AB  - Mouse bone marrow-derived cells implanted into freeze-injured bladder walls form
      smooth muscle layers, but not in intact walls. We determined if the
      microenvironment within injured urinary bladders was supportive of smooth muscle
      layer development. The urinary bladders of female nude mice were freeze-injured
      for 30 s. Three days later, the rate of blood flow in the wounded areas and in
      comparable areas of intact control urinary bladders was observed by charge
      coupled device (CCD) video microscopy. Injured and control bladder walls were
      also analyzed histologically and cytologically. Growth factor mRNA expression was
      determined by real-time reverse transcription polymerase chain reaction arrays.
      The injured regions maintained a partial microcirculation in which blood flow
      velocity was significantly less than in controls. The injured bladder walls had
      few typical smooth muscle layers, and blood vessels in the walls had reduced
      smooth muscle content. The loss of smooth muscle cells in the bladder walls may
      have resulted in the formation of large porous spaces seen by scanning electron
      microscopy of the injured areas. The expression of nineteen growth-related mRNAs,
      including secreted phosphoprotein 1, inhibin beta-A, glial cell line-derived
      neurotrophic factor, and transforming growth factor beta1, were significantly
      upregulated in the injured urinary bladders. In conclusion, the microenvironment
      in freeze-injured urinary bladders enables successful tissue engineering.

PMID- 19397472
TI  - Ultraviolet treatment overcomes time-related degrading bioactivity of titanium.
AB  - The shelf life of titanium implant products, that is, a possible time-related
      change of their bioactivity, has rarely been addressed. The objective of this
      study was to examine the bioactivity of newly processed and aged titanium
      surfaces and determine whether ultraviolet (UV) light treatment of the titanium
      surface restores the possible adverse effects of titanium aging. Titanium disks,
      either acid-etched or sandblasted, were used immediately after processing (fresh
      surface) or after storing in dark for 4 weeks (aged surface). Some disks were
      treated with UV light for 48 h after 4 weeks of storage. Albumin adsorbed to the
      aged surfaces was only 15% of that adsorbed to the fresh surfaces during 2-h
      incubation, whereas UV-treated aged surfaces adsorbed equivalent amount of
      albumin to that for the fresh surfaces. During 24-h incubation, the number of
      human mesenchymal stem cells attached to the aged surfaces was less than half of
      that for the fresh surfaces, whereas UV treatment of the aged surfaces increased
      the number three times. Proliferation, alkaline phosphatase activity, and calcium
      deposition of the cells were substantially lower on the aged surfaces than on the
      fresh surfaces, while those on the UV-treated aged surfaces were higher than on
      the fresh surfaces. The strength of bone-implant integration evaluated at week 2
      of healing in a rat femur model was reduced to half after 4 weeks of titanium
      aging, whereas UV treatment of the aged implants increased the strength to the
      level equivalent to or even higher than the freshly prepared implants. Fresh and
      UV-treated aged surfaces were superhydrophilic, while the aged surface was
      hydrophobic. The data suggest that bioactivity of titanium surfaces degrades with
      time and that UV treatment of the aged surface increases the bioactivity over the
      level of the freshly prepared surface.

PMID- 19397473
TI  - Use of a rotary bioartificial liver in the differentiation of human liver stem
      cells.
AB  - The use of bioartificial livers (BALs) for the expansion of human adult liver
      stem cells and the production of growth factors could be a potential strategy for
      cell-based extracorporeal liver support. The present study aimed to assessing the
      differentiation of human adult liver stem cells in a rotary BAL. Liver stem cells
      were seeded into a polysulphone membrane filter at a density of 3 x 10(8) cells,
      and the filter was connected to a rotary bioreactor perfusion system (37 degrees
      C, 50 mL/min, 48 h). Viability, cell differentiation, and metabolic performances
      were evaluated at 24 and 48 h. Hepatocyte growth factor production from human
      adult liver stem cells, mature hepatocytes, and mesenchymal stem cells in
      adhesion and in the rotary BAL conditions was compared. Liver stem cells cultured
      in the rotary BAL produced the highest amounts of albumin (p = 0.002) and ammonia
      induced urea (p = 0.0001), and had an increased cytochrome P450 expression in
      respect to liver stem cells in adhesion. Remarkably, liver stem cells in the
      rotary BAL produced very high amounts of hepatocyte growth factor (p = 0.005) in
      respect to hepatocytes and mesenchymal stem cells. Moreover, the cells lost their
      stem cell markers and acquired several markers of mature hepatocytes. In
      conclusion, the rotary BAL favored liver stem cell differentiation into mature
      hepatocyte-like cells.

PMID- 19397474
TI  - Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in
      non-diabetic proteinuric patients: relationships with cholesteryl ester transfer
      protein mass and adiponectin.
AB  - OBJECTIVE: Dyslipidemia contributes to increased cardiovascular risk in nephrotic
      syndrome. We questioned whether reduction in proteinuria not only lowers low
      density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein
      cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP) mass and
      whether changes in HDL-C were related to changes in plasma adiponectin. METHODS:
      Thirty-two non-diabetic proteinuric patients (12 on statin therapy), were
      followed during two double blind 6-week periods of placebo and treatment (low
      sodium + 100mg losartan + 25 mg hydrochlorothiazide). RESULTS: With placebo HDL-C
      was lower but LDL-C and CETP were not different in proteinuric patients compared
      with matched controls. LDL-C, HDL-C and CETP decreased upon proteinuria
      reduction. The decrease in LDL-C correlated with the drop in CETP and the degree
      of proteinuria reduction. HDL-C also decreased in proportion to proteinuria
      lowering. Individual changes in HDL-C were correlated with changes in
      adiponectin. CONCLUSION: LDL-C lowering upon robust reduction of proteinuria may
      be affected by changes in plasma CETP mass, but this treatment also decreases HDL
      C in relation to the degree of proteinuria reduction. This adverse effect on HDL
      C may in part be attributable to changes in adiponectin.

PMID- 19397476
TI  - Inhibition of HGF/MET as therapy for malignancy.
AB  - BACKGROUND: Inhibition of inappropriate tyrosine kinase activity by neoplasms is
      an attractive strategy for the treatment of malignancy. OBJECTIVE: We aimed to
      produce a concise review of the potential role of hepatocyte growth factor
      (HGF)/Mesenchymal-epithelial transition factor (MET) tyrosine kinase pathway
      inhibition in the treatment of cancer. METHODS: The current literature, abstracts
      and internet resources related to HGF/MET structure, function and inhibition are
      summarized. The potential of inhibiting this pathway as a therapy for cancer and
      remaining hurdles prior to routine clinical use of MET inhibition are discussed.
      RESULTS/CONCLUSIONS: Current knowledge suggests that the inhibition of the
      HGF/MET pathway has significant potential for the treatment of cancer. A number
      of MET inhibitor molecules are nearing completion of their development for
      clinical use.

PMID- 19397477
TI  - Novel factors as therapeutic targets to treat diabetes. Focus on leptin and
      ghrelin.
AB  - BACKGROUND: Obesity is the major cause of type 2 diabetes. In the mid 1990s
      interest in adipose tissue was revived by the discovery of leptin. The
      association of obesity and diabetes emphasizes their shared physiopathological
      features. At the end of the 1990s, ghrelin, a potent gastric orexigenic factor,
      was found to be involved in obesity. Leptin and ghrelin have opposite actions in
      several tissues including the regulation of feeding in the brain.
      OBJECTIVE/METHODS: To survey the role of leptin and ghrelin in glucose
      metabolism. We summarize the current state of research and discuss the roles of
      ghrelin and leptin in glucose homeostases and the potential application of drugs
      targeting leptin and ghrelin signalling to prevent and treat diabetes.
      RESULTS/CONCLUSIONS: A pressing challenge is to determine how leptin, ghrelin and
      other adipokines or gastric factors are involved in metabolic disorders.
      Answering these questions will require the development of new pharmacological
      tools that target specific adipokine systems. Hopefully, new therapeutic targets
      will be identified.

PMID- 19397478
TI  - Molecular switching of osteoblastogenesis versus adipogenesis: implications for
      targeted therapies.
AB  - Osteoblasts and adipocytes differentiate from a common precursor, the pluripotent
      mesenchymal stem cell (MSC) found in bone marrow (BMSC) and adipose tissue (AD
      MSC). Numerous transcription factors and multiple extracellular and intracellular
      signals regulating adipogenesis and osteoblastogenesis have been identified and
      analyzed. Significantly, inducers of differentiation towards one lineage may
      inhibit cell differentiation into an alternative lineage. For example, the
      canonical Wnt/beta-catenin pathway induces osteoblastogenesis and inhibits
      adipogenesis, whereas the peroxisome proliferator activated receptor-gamma (PPAR
      gamma) is a prime inducer of adipogenesis and, as shown in recent studies,
      inhibits osteoblastogenesis. We have identified two signaling pathways that
      switch the cell fate decision from adipocytes to osteoblasts by suppressing the
      transactivation function of PPAR-gamma. In the first pathway, the TNF-alpha- or
      IL-1-induced TAK1/TAB1/NIK signaling cascade attenuates PPAR-gamma-mediated
      adipogenesis by inhibiting the binding of PPAR-gamma to the DNA response element.
      The second is the noncanonical Wnt pathway through the CaMKII-TAK1/TAB2-NLK (nemo
      like kinase) signaling cascade. Specifically, Wnt-5a-induced phosphorylation of
      NLK triggers formation of a complex with the histone methyltransferase SETDB1
      (SET domain, bifurcated 1) that represses PPAR-gamma transactivation through
      histone H3-K9 methylation at the target genes. Thus, two signaling cascades
      promote osteoblastic differentiation from MSC through two distinct modes of PPAR
      gamma transrepression.

PMID- 19397475
TI  - ADAM8: a new therapeutic target for asthma.
AB  - BACKGROUND: A proteinase with a disintegrin and a metalloproteinase domain-8
      (ADAM8) has been linked to asthma. OBJECTIVE: To explore whether ADAM8 is a
      therapeutic target for asthma. METHODS: We reviewed literature on ADAM8's
      function and expression and activities in lungs of humans and mice with allergic
      airway inflammation (AAI). We used these data to generate hypotheses about the
      contributions of ADAM8 to asthma pathogenesis. CONCLUSIONS: ADAM8 levels are
      increased in airway epithelium and airway inflammatory cells in mice with AAI and
      human asthma patients. Data from murine models of AAI indicate that ADAM8 dampens
      airway inflammation. It is not clear whether ADAM8 contributes directly to
      structural remodeling in asthmatic airways. Additional studies are required to
      validate ADAM8 as a therapeutic target for asthma.

PMID- 19397479
TI  - Targeting the proteasome pathway.
AB  - BACKGROUND: The ubiquitin-proteasome pathway functions as a main pathway in
      intracellular protein degradation and plays a vital role in almost all cellular
      events. Various inhibitors of this pathway have been developed for research
      purposes. The recent approval of bortezomib (PS-341, Velcade, a proteasome
      inhibitor, for the treatment of multiple myeloma has opened the way to the
      discovery of drugs targeting the proteasome and other components of the ubiquitin
      proteasome pathway. OBJECTIVES: We review the current understanding of the
      ubiquitin-proteasome pathway and inhibitors targeting this pathway, including
      proteasome inhibitors, as candidate drugs for chemical therapy. METHODS:
      Preclinical and clinical data for inhibitors of the proteasome and the ubiquitin
      proteasome pathway are discussed. CONCLUSIONS: The proteasome and other members
      in the ubiquitin-proteasome pathway have emerged as novel therapeutic targets.

PMID- 19397481
TI  - Pharmacogenetics of vitamin K antagonists: useful or hype?
AB  - Oral anticoagulant therapy (OAT) based on vitamin K antagonists (VKAs; coumarin
      derivatives) is the current mainstay for the prevention and long-term treatment
      of a variety of thromboembolic disorders. Care of patients on OAT is challenging
      due to considerable variability in the response to a particular dose. This has
      been attributed to environmental, demographic, clinical and genetic variables.
      Individualized responses represent a major clinical challenge because patients
      may experience adverse health outcomes from bleeding or thrombosis as a result of
      over- or under-coagulation, respectively. Growing evidence indicates that up to
      60% of the individual pharmacological response to coumarins might be due to
      genetic variables and affected by polymorphisms in the genes encoding two
      enzymes, namely, vitamin K epoxide reductase (VKOR) and cytochrome P450 CYP2C9.
      Genetic testing has been proposed as a useful tool for allowing prediction of the
      dose response during initial anticoagulation therapy, to assess variability in
      dose maintenance and to identify warfarin 'resistance'. However, genetic testing
      is not a panacea. Limitations include the optimal composition of test panels,
      still largely unknown, information concerning inter-individual variability, lack
      of analytical and quality specifications, lack of comprehensive outcome analyses
      to enable assessment of cost-effectiveness, lack of universal agreement related
      to reliable dosing algorithms and other ethical and social issues. The aim of
      this article is to provide a comprehensive overview of our current understanding
      of the pharmacogenetics of VKAs, as well as assessing potential advantages and
      limitations. Although it might be premature to recommend routine genetic testing,
      the future development and clinical validation of simple but comprehensive
      algorithms integrating the most informative gene polymorphisms (VKORC1 and
      CYP2C9) with some demographic information (age, race, body mass index) and
      clinical variables (comorbidities, drugs interference), and standardized dietary
      intake of vitamin K may provide a valuable tool in the care of patients on OAT
      with conventional VKAs. However, the ongoing development of new anticoagulant
      drugs targeting thrombin and factor X will introduce a paradigm shift in long
      term anticoagulation therapy, so that consideration could be given to demise
      pharmacogenetics testing for VKAs.

PMID- 19397482
TI  - Illumina DNA test panel-based genotyping of whole genome amplified-DNA extracted
      from hair samples: performance and agreement with genotyping results from genomic
      DNA from buccal cells.
AB  - BACKGROUND: Hair is a DNA source that can be collected easily and inexpensively
      from participants in epidemiological studies. However, there is concern about DNA
      quality and quantity. Therefore, we assessed genotyping performance of whole
      genome amplified (WGA)-DNA extracted from hair using the GenomePlex method and
      evaluated its agreement with genotyping results of buccal cell DNA from the same
      individuals, using the Illumina GoldenGate platform. METHODS: The Illumina DNA
      test panel includes 360 highly validated single nucleotide polymorphisms (SNPs)
      selected from the Linkage IV Panel that are distributed across the entire genome.
      DNA was extracted from both archived hair and buccal cell samples obtained from
      44 randomly selected subjects participating in a large cohort study in Canada.
      RESULTS: The genotyping success rate was 97.7% for 44 paired samples. However,
      WGA-DNA from hair failed more during genotyping in comparison to buccal cell DNA.
      Hair samples with a pre-WGA-DNA>or=1 ng/microL quantified using the PicoGreen
      assay (n=33) showed an average genotyping completion rate of 98.8% and SNP
      concordance of 91.2% with genotyping performance of buccal cell DNA. In contrast,
      samples with a pre-WGA-DNA<1 ng/microL had lower genotyping completion rate (94%)
      and poor SNP concordance (49%). CONCLUSIONS: Results suggest that WGA-DNA
      obtained from hair can produce excellent genotyping call rates and show
      relatively good SNP concordance with results from buccal cell DNA using high
      throughput technology. DNA quantity obtained from hair samples is a crucial
      determinant of genotyping performance. Larger studies are needed to examine the
      utility of hair DNA with different genotyping platforms.

PMID- 19397484
TI  - Hematocytometry analysis as discriminative marker for asthma phenotypes.
AB  - BACKGROUND: There is an increasing demand for easy to measure biomarkers in
      clinical practice. We created the relational database Utrecht Patient Oriented
      Database (UPOD) to develop tools for identifying new biomarkers for disease. In
      this study, we used UPOD to identify better biomarkers for discriminating
      different asthma phenotypes. METHODS: We performed a prospective study at the
      University Medical Center (UMC) Utrecht using blood from patients with asthma and
      a healthy reference group. Since asthma is an inflammatory disease, absolute
      leukocyte counts and leukocyte differential parameters were analyzed using raw
      data files and a logistic regression model. RESULTS: We compared 17 difficult-to
      treat asthma (DTA) cases, 13 non-difficult-to-treat asthma cases, and 19 healthy
      volunteers. Absolute leukocyte counts and differential parameters for leukocytes
      were able to discriminate asthma patients from healthy volunteers. However, among
      patients with asthma, difficult-to-treat cases could be more accurately defined
      with a neutrophil morphology change (OR 8.0; 95% CI 1.5-42.0), compared to the
      absolute neutrophil count (OR 4.0; 95% CI 0.8-21.0). CONCLUSIONS: In this asthma
      patient population, we were able to define asthma phenotypes more precisely using
      neutrophil morphology parameters, compared to absolute counts. Using UPOD with
      differential parameters, it is possible to conduct larger scale biomarker
      studies, combining clinical, laboratory medicine, and epidemiological techniques.

PMID- 19397483
TI  - Determination of volatile organic compounds in exhaled breath of patients with
      lung cancer using solid phase microextraction and gas chromatography mass
      spectrometry.
AB  - BACKGROUND: Analysis of exhaled breath is a promising diagnostic method. Sampling
      of exhaled breath is non-invasive and can be performed as often as considered
      desirable. There are indications that the concentration and presence of certain
      of volatile compounds in exhaled breath of lung cancer patients is different from
      concentrations in healthy volunteers. This might lead to a future diagnostic test
      for lung cancer. METHODS: Exhaled breath samples from 65 patients with different
      stages of lung cancer and undergoing different treatment regimes were analysed.
      Mixed expiratory and indoor air samples were collected. Solid phase
      microextraction (SPME) with carboxen/polydimethylsiloxane (CAR/PDMS) sorbent was
      applied. Compounds were analysed by means of gas chromatography (GC) and mass
      spectrometry (MS). RESULTS: The method we used allowed identification with the
      spectral library of 103 compounds showing at least 15% higher concentration in
      exhaled breath than in inhaled air. Among those 103 compounds, 84 were confirmed
      by determination of the retention time using standards based on the respective
      pure compound. Approximately, one third of the compounds detected were
      hydrocarbons. We found aromatic hydrocarbons, alcohols, aldehydes, ketones,
      esters, ethers, sulfur compounds, nitrogen-containing compounds and halogenated
      compounds. Acetonitrile and benzene were two of 10 compounds which correlated
      with smoking behaviour. A comparison of results from cancer patients with those
      of 31 healthy volunteers revealed differences in the concentration and presence
      of certain compounds. The sensitivity for detection of lung cancer patients based
      on eight different compounds not seen in exhaled breath of healthy volunteers was
      51% and the specificity was 100%. These eight potential markers for detection of
      lung cancer are 1-propanol, 2-butanone, 3-butyn-2-ol, benzaldehyde, 2-methyl
      pentane, 3-methyl-pentane, n-pentane and n-hexane. CONCLUSIONS: SPME is a
      relatively insensitive method and compounds not observed in exhaled breath may be
      present at a concentration lower than LOD. The main achievement of the present
      work is the validated identification of compounds observed in exhaled breath of
      lung cancer patients. This identification is indispensible for future work on the
      biochemical sources of these compounds and their metabolic pathways.

PMID- 19397485
TI  - Serum beta2-microglobulin measured by immunonephelometry: expression patterns and
      reference intervals in healthy adults.
AB  - BACKGROUND: Serum beta2-microglobulin (beta2m) has been established as a marker
      of disease activity in malignancies, autoimmune conditions and infections.
      Despite its important role in prognosis assessment and disease monitoring,
      relatively few studies are available on its expression in healthy individuals.
      Furthermore, interpretation of results is hampered by the variety in reference
      limits due to differences in methodology, sample population and statistics.
      METHODS: Serum beta2m concentrations were measured using a microparticle-enhanced
      immunonephelometric method in 183 healthy blood donors aged 29-75 years. RESULTS:
      The median beta2m concentration was 1.67 (0.88-2.75) mg/L with no difference
      between men and women (1.71 mg/L vs. 1.62 mg/L, p<0.07). A linear correlation was
      found between beta2m and age (p<0.0001), serum concentrations significantly
      higher in older subjects (1.55, 1.59, 1.70, and 1.87 mg/L in age groups of 29-40,
      40-50, 50-60 and 60-75 years, respectively, p<0.0001). Reference intervals
      obtained by non-parametric estimation after partitioning by age were 1.02-2.46
      mg/L vs. 1.29-2.70 mg/L in younger (29-49 years) vs. older (50-75 years)
      individuals. CONCLUSIONS: These data can help standardise beta2m reference limits
      and support age-adjusted comparisons in clinical studies.

PMID- 19397486
TI  - Spuriously high thyrotropin values due to anti-thyrotropin antibodies in adult
      patients.
AB  - BACKGROUND: Three adult patients presented with unexpectedly high thyrotropin
      (TSH) concentrations that were discordant with clinical and biochemical findings
      of euthyroid or hyperthyroid status. METHODS: Antibody interference in the TSH
      immunoassay (Roche) was investigated by polyethylene glycol (PEG)-pretreatment,
      heterophilic blocking tube (HBT)-pretreatment, rheumatoid factor (RF) testing,
      immunofixation, protein A adsorption, and gel filtration chromatography (GFC).
      RESULTS: PEG-precipitation yielded<20% recovery of serum TSH, whereas HBT
      pretreatment did not decrease TSH test results. RF-testing and immunofixation
      were negative. Protein A adsorption and GFC demonstrated the presence of TSH
      immunoglobulin complexes in serum. CONCLUSIONS: Interference by TSH
      immunoglobulin complexes should be ruled out in euthyroid and hyperthyroid
      patients presenting with inappropriately increased or non-suppressed TSH values.

PMID- 19397487
TI  - Workflow restrictions on hematology analyzers XE-2100 and XS-800 when assaying
      pediatric samples with limited volume.
AB  - BACKGROUND: Samples with limited volume is a common problem in laboratories
      receiving samples from pediatric patients. Also, pediatric samples may contain
      nucleated red blood cells (NRBC) which distorts the white blood cell (WBC) count
      and which can only be measured by some automated cell counting systems.
      Differential counts are sometimes required, posing the question of validity of
      flagging depending on age of the patients and on predilutions. METHODS: We
      evaluated the hematology analyzers XE-2100 and XS-800 for their suitability in
      measuring hematological parameters in such samples. RESULTS: With the exception
      of the MCHC and partly the MCH, we observed very good agreement between complete
      blood counts (CBC) in diluted and undiluted samples. Dilution did not impair
      sensitivity in the clinically relevant range nor, accuracy of the NRBC count on
      XE-2100. Flagging was ineffective in undiluted samples from children<1 year of
      age and in all diluted samples when measuring differential counts. CONCLUSIONS:
      In summary, while automated measurement of CBC and NRBC is possible in diluted
      samples, measurement of differential counts is restricted by loss of flagging
      efficiency. In addition, flagging is also ineffective in children<1 year of age
      using the analyzers evaluated and should, for diagnostic purposes, be performed
      manually.

PMID- 19397488
TI  - Carbamylated hemoglobin remains a critical issue in HbA1c measurements.

PMID- 19397489
TI  - Quantitative scanning analysis of a cryoglobulin ring detected in sera of
      patients with hepatitis C using a cooling gel diffusion method.

PMID- 19397490
TI  - Significant reduction of erythrocyte glucose-6-phosphate dehydrogenase activity
      in soccer-players during play. Evidence for catecholamine mediated enzyme
      inhibition.

PMID- 19397491
TI  - Phosphoinositide 3-kinases and their role in inflammation: potential clinical
      targets in atherosclerosis?
AB  - Inflammation has a central role in the pathogenesis of atherosclerosis at various
      stages of the disease. Therefore it appears of great interest to develop novel
      and innovative drugs targeting inflammatory proteins for the treatment of
      atherosclerosis. The PI3K (phosphoinositide 3-kinase) family, which catalyses the
      phosphorylation of the 3-OH position of phosphoinositides and generates
      phospholipids, controls a wide variety of intracellular signalling pathways.
      Recent studies provide evidence for a crucial role of this family not only in
      immune function, such as inflammatory cell recruitment, and expression and
      activation of inflammatory mediators, but also in antigen-dependent responses
      making it an interesting target to modulate inflammatory processes. The present
      review will focus on the regulation of inflammation within the vasculature during
      atherogenesis. We will concentrate on the different functions played by each
      isoform of PI3K in immune cells which could be involved in this pathology,
      raising the possibility that inhibition of one or more PI3K isoforms may
      represent an effective approach in the treatment of atherosclerosis.

PMID- 19397493
TI  - Strategies for analysing and improving the expression and quality of recombinant
      proteins made in mammalian cells.
AB  - The production of monoclonal antibodies and other recombinant proteins is one of
      the highest growth areas in the pharmaceutical industry. Mammalian cells are used
      to manufacture the majority of biotherapeutics, largely due to their ability to
      perform complex post-translational modifications. Although significant progress
      has been made recently in improving product yields and protein quality, many
      challenges still lie ahead to achieve consistently high yields while avoiding
      potentially damaging protein modifications. The present review first considers
      the strategies used to analyse and improve recombinant protein expression of
      industrial cell lines, with an emphasis on proteomic technologies. Next, cellular
      and environmental influences on protein production and quality are examined, and
      strategies for improvements in product yield and quality are reviewed. The
      analytical techniques required to detect these protein changes are also
      described, together with prospects for assay improvements.

PMID- 19397492
TI  - Receptor-associated protein (RAP) has two high-affinity binding sites for the low
      density lipoprotein receptor-related protein (LRP): consequences for the
      chaperone functions of RAP.
AB  - RAP (receptor-associated protein) is a three domain 38 kDa ER (endoplasmic
      reticulum)-resident protein that is a chaperone for the LRP (low-density
      lipoprotein receptor-related protein). Whereas RAP is known to compete for
      binding of all known LRP ligands, neither the location, the number of binding
      sites on LRP, nor the domains of RAP involved in binding is known with certainty.
      We have systematically examined the binding of each of the three RAP domains (D1,
      D2 and D3) to tandem and triple CRs (complement-like repeats) that span the
      principal ligand-binding region, cluster II, of LRP. We found that D3 binds with
      low nanomolar affinity to all (CR)2 species examined. Addition of a third CR
      domain increases the affinity for D3 slightly. A pH change from 7.4 to 5.5 gave
      only a 6-fold increase in Kd for D3 at 37 degrees C, whereas temperature change
      from 22 degrees C to 37 degrees C has a similar small effect on affinity, raising
      questions about the recently proposed D3-destabilization mechanism of RAP release
      from LRP. Surprisingly, and in contrast to literature suggestions, D1 and D2 also
      bind to most (CR)2 and (CR)3 constructs with nanomolar affinity. Although this
      suggested that there might be three high-affinity binding sites in RAP for LRP,
      studies with intact RAP showed that only two binding sites are available in the
      intact chaperone. These findings suggest a new model for RAP to function as a
      folding chaperone and also for the involvement of YWTD domains in RAP release
      from LRP in the Golgi.

PMID- 19397494
TI  - Methanol-inducible gene expression and heterologous protein production in the
      methylotrophic yeast Candida boidinii.
AB  - Methylotrophic yeasts can obtain all of their required carbon and energy from
      methanol, a promising feedstock for biotechnological and chemical processes and a
      potential replacement for coal and petroleum. When these yeast cells are cultured
      in the presence of methanol, the enzymes involved in methanol metabolism are
      massively produced, indicating that the gene promoters of these enzymes are
      strong methanol-inducible promoters. Using these promoters, high-level
      heterologous gene expression systems have been developed in several
      methylotrophic yeast strains, including Pichia pastoris, Hansenula polymorpha,
      Pichia methanolica and Candida boidinii. In the present minireview we describe
      recent insights into the molecular basis of methanol-inducible gene expression in
      C. boidinii. In addition, the utility of C. boidinii gene expression systems for
      the production of various enzymes is also reviewed.

PMID- 19397495
TI  - Post-transcriptional regulation of gene expression in yeast under ethanol stress.
AB  - The selective export of mRNA from the nucleus plays an important role in the
      regulation of yeast gene expression under ethanol-stressed conditions, and it has
      been clarified that expression of the transcriptionally activated HSP (heat-shock
      protein) genes are inhibited in the mRNA processing and export steps. In actual
      alcoholic fermentation, during the late brewing process for wine in which the
      ethanol concentration has been increased, the export of bulk poly(A)+
      (polyadenylated) mRNA is blocked and protein synthesis is considerably repressed.
      These observations clearly suggest that variation in the mRNA level is not
      necessarily reflected in the variation of the protein level in yeast cells during
      the brewing process. The present minireview outlines the regulation of yeast gene
      expression at the mRNA-processing and nuclear-export steps under ethanol-stressed
      conditions, highlighting their usefulness in the brewing industry.

PMID- 19397497
TI  - Cerebral epidural hematoma following cerebrospinal fluid drainage during
      thoracoabdominal aortic repair.
AB  - Cerebrospinal fluid (CSF) drainage is a common adjunct to thoracoabdominal aortic
      aneurysm (TAAA) repair. CSF drainage may improve perioperative spinal cord
      perfusion and thereby decrease the incidence of paraplegia or paraparesis.
      Complications of CSF drainage may arise. We present a case of cerebral epidural
      hematoma (EDH), possibly arising from excessive CSF drainage, during
      thoracoabdominal aortic repair.

PMID- 19397496
TI  - The RhoU/Wrch1 Rho GTPase gene is a common transcriptional target of both the
      gp130/STAT3 and Wnt-1 pathways.
AB  - STAT3 (signal transducer and activator of transcription 3) is a transcription
      factor activated by cytokines, growth factors and oncogenes, whose activity is
      required for cell survival/proliferation of a wide variety of primary tumours and
      tumour cell lines. Prominent among its multiple effects on tumour cells is the
      stimulation of cell migration and metastasis, whose functional mechanisms are
      however not completely characterized. RhoU/Wrch1 (Wnt-responsive Cdc42 homologue)
      is an atypical Rho GTPase thought to be constitutively bound to GTP. RhoU was
      first identified as a Wnt-1-inducible mRNA and subsequently shown to act on the
      actin cytoskeleton by stimulating filopodia formation and stress fibre
      dissolution. It was in addition recently shown to localize to focal adhesions and
      to Src-induced podosomes and enhance cell migration. RhoU overexpression in
      mammary epithelial cells stimulates quiescent cells to re-enter the cell cycle
      and morphologically phenocopies Wnt-1-dependent transformation. In the present
      study we show that Wnt-1-mediated RhoU induction occurs at the transcriptional
      level. Moreover, we demonstrate that RhoU can also be induced by gp130 cytokines
      via STAT3, and we identify two functional STAT3-binding sites on the mouse RhoU
      promoter. RhoU induction by Wnt-1 is independent of beta-catenin, but does not
      involve STAT3. Rather, it is mediated by the Wnt/planar cell polarity pathway
      through the activation of JNK (c-Jun N-terminal kinase). Both the so-called non
      canonical Wnt pathway and STAT3 are therefore able to induce RhoU, which in turn
      may be involved in mediating their effects on cell migration.

PMID- 19397498
TI  - Pulmonary edema in the transurethral resection syndrome induced with mannitol 5%.
AB  - Two patients developed the transurethral resection (TUR) syndrome after having
      absorbed mannitol 5% during TUR of the prostate. Both developed pulmonary edema
      and became severely hypoatremic (lowest serum sodium 99 and 97 mmol/l,
      respectively). Hypertonic saline was infused to raise the serum sodium level and
      plasma volume expansion used to combat hypotension. One patient also required
      positive-pressure ventilation and intravenous administration of norepinephrine.
      Both patients recovered completely.

PMID- 19397499
TI  - Soft tissue landmark for ultrasound identification of the sciatic nerve in the
      infragluteal region: the tendon of the long head of the biceps femoris muscle.
AB  - BACKGROUND AND OBJECTIVES: The sciatic nerve block represents one of the more
      difficult ultrasound-guided nerve blocks. Easy and reliable internal ultrasound
      landmarks would be helpful for localization of the sciatic nerve. Earlier, during
      ultrasound-guided posterior approaches to the infragluteal sciatic nerve, the
      authors recognized a hyperechoic structure at the medial border of the long head
      of biceps femoris muscle (BFL). The present study was performed to determine
      whether this is a potential internal landmark to identify the infragluteal
      sciatic nerve. METHODS: The depth and the thickness of this hyperechoic
      structure, its relationship with the sciatic nerve and the ultrasound visibility
      of both were recorded in the proximal upper leg of 21 adult volunteers using a
      linear ultrasound probe in the range of 7-13 MHz. The findings were verified by
      an anatomical study in two cadavers. RESULTS: The hyperechoic structure at the
      medial border of the BFL extended in a dorsoventral direction between 1.4+/-0.6
      cm (mean+/-SD) and 2.8+/-0.8 cm deep from the surface, with a width of 2.2+/-0.9
      mm. Between 2.6+/-0.9 and 10.0+/-1.5 cm distal to the subgluteal fold, the
      sciatic nerve was consistently identified directly at the ventral end of the
      hyperechoic structure in all volunteers. The anatomical study revealed that this
      hyperechoic structure corresponds to tendinous fibres inside and at the medial
      border of the BFL. CONCLUSION: The hyperechoic BFL tendon might be a reliable
      soft tissue landmark for ultrasound localization of the infragluteal sciatic
      nerve.

PMID- 19397500
TI  - Extremely prolonged neuromuscular blockade after rocuronium: a case report.
AB  - It is known that the duration of rocuronium action can be prolonged in elderly
      patients and that such action shows important interindividual variability. We
      report a case of prolonged neuromuscular block lasting 11 h, in a woman subjected
      to kidney transplantation. The possible causes of such prolonged action, inherent
      to the drug, or related to external factors, are commented.

PMID- 19397501
TI  - Circulatory arrest in late pregnancy: caesarean section a vital decision for both
      mother and child.
AB  - Circulatory arrest during pregnancy is extremely rare and there should be a well
      planned strategy for its management in all hospitals. To consider the priority of
      the mother's life over the child's and an unwarranted pre-term delivery may lead
      to hesitancy and uncertainty and jeopardize both of them. In these situations,
      speed is a priority. Cardiopulmonary resuscitation should commence immediately.
      The anaesthesiologist should be well aware of the possible advantage of a
      caesarean section. Even if the obstetrician is responsible for the decision to
      perform the operation, the anaesthesiologist should strongly support the action.
      An 'emergency caesarean kit' with the essential surgical instruments should be
      immediately available in every labour ward and emergency department.

PMID- 19397502
TI  - Pulse oximeter perfusion index as an early indicator of sympathectomy after
      epidural anesthesia.
AB  - BACKGROUND: The pulse oximeter perfusion index (PI) has been used to indicate
      sympathectomy-induced vasodilatation. We hypothesized that pulse oximeter PI
      provides an earlier and clearer indication of sympathectomy following epidural
      anesthesia than skin temperature and arterial pressure. METHODS: Forty patients
      received lumbar epidural catheters. Patients were randomized to receive either 10
      ml 0.5% bupivacaine or 10 ml 0.25% bupivacaine. PI in the toe, mean arterial
      pressure (MAP) and toe temperature were all assessed at baseline and at 5, 10 and
      20 min following epidural anesthesia. The effect of epidural anesthesia over time
      was assessed by repeated measures analysis of variance. Additionally, we defined
      clinically evident sympathectomy criteria (a 100% increase in the PI, a 15%
      decrease in MAP and a 1 degrees C increase in toe temperature). The numbers of
      patients demonstrating these changes for each test were compared using the
      McNemar test for each time point. RESULTS: Twenty-nine subjects had
      photoplethysmography signals that met a priori signal quality criteria for
      analysis. By 20 min, PI increased by 326%, compared with a 10% decrease and a 3%
      increase in MAP and toe temperature, respectively. For PI 15/29, 26/29 and 29/29
      of the subjects met the sympathectomy criteria at 5, 10 and 20 min, respectively,
      compared with 4/29, 6/29 and 18/29 for MAP changes and 3/29, 8/29 and 14/29 for
      toe temperature changes. CONCLUSIONS: PI was an earlier, clearer and more
      sensitive indicator of the development of epidural-induced sympathectomy than
      either skin temperature or MAP.

PMID- 19397503
TI  - Oxytocin infusion: acute hyponatraemia, seizures and coma.
AB  - Hyponatremia is not uncommon, serious cases can cause dangerous complications as
      seizures, brain damage and even death. We present a case of a young mother with
      post partum hemorrhage and some of the serious complications.

PMID- 19397504
TI  - Influence of hypobaric hypoxia on bispectral index and spectral entropy in
      volunteers.
AB  - BACKGROUND: Hypoxia has been shown to change electroencephalogram parameters
      including frequency and amplitude, and may thus change bispectral index (BIS) and
      spectral entropy values. If hypoxia per se changes BIS and spectral entropy
      values, BIS and spectral entropy values may not correctly reflect the depth of
      anaesthesia during hypoxia. The aim of this study was to examine the changes in
      BIS and spectral entropy values during hypobaric hypoxia in volunteers. METHODS:
      The study was conducted in a high-altitude chamber with 11 volunteers. After the
      subjects breathed 100% oxygen for 15 min at the ground level, the simulated
      altitude increased gradually to the 7620 m (25,000 ft) level while the subjects
      continued to breathe oxygen. Then, the subjects discontinued to breath oxygen and
      breathed room air at the 7620 m level for up to 5 min until they requested to
      stop hypoxic exposure. Oxygen saturation (SpO2), heart rate, 95% spectral edge
      frequency (SEF), BIS, response entropy (RE), and state entropy (SE) of spectral
      entropy were recorded throughout the study period. RESULTS: Of the 11 subjects,
      seven subjects who underwent hypoxic exposure for 4 min were analysed. SpO2
      decreased to 69% at the 7620 m level without oxygen. However, SEF, BIS, RE, and
      SE before and during hypoxic exposure were almost identical. CONCLUSION: These
      data suggest that hypoxia of oxygen saturation around 70% does not have a strong
      effect on BIS and spectral entropy.

PMID- 19397505
TI  - Sensory function and pain in a population of patients treated for breast cancer.
AB  - BACKGROUND: Chronic pain is often reported after surgery for breast cancer. This
      study examined pain and sensory abnormalities in women following breast cancer
      surgery. METHODS: Sensory tests were carried out on the operated and contra
      lateral side in 55 women with chronic pain after breast cancer treatment and in a
      reference group of 27 pain-free women, who had also undergone treatment for
      breast cancer. Testing included a numeric rating score of spontaneous pain,
      detection and pain threshold to thermal and dynamic mechanical stimuli and
      temporal summation to repetitive pinprick stimulation. The neuropathic pain
      symptom inventory was applied for participants with chronic pain. RESULTS: The
      mean age was 58.6 years for the pain patients and 60.6 years for the pain-free
      patients. Thermal thresholds were significantly higher on the operated side than
      on the contra-lateral side in both groups and side difference in warmth detection
      threshold was significantly higher in the pain group than in the pain-free group
      (mean 3.8 degrees C vs. 1.1 degrees C, P=0.01). The frequency of cold allodynia
      was higher in participants with pain than in pain-free participants (15/53 vs.
      1/25, P=0.01), and the frequency of temporal summation evoked by repetitive
      pinprick was higher in participants with pain than in pain-free participants
      (23/53 vs. 2/25, P=0.0009). The frequency of dynamic mechanical allodynia did not
      differ significantly between the two groups. CONCLUSION: These findings suggest
      that chronic pain after surgery for breast cancer is associated with sensory
      hyperexcitability and is a neuropathic pain condition.

PMID- 19397506
TI  - Anaesthesiological considerations on tocolytic and uterotonic therapy in
      obstetrics.
AB  - AIM: Significant side effects of tocolytic and uterotonic substances may be of
      concern to the anaesthesiologist. Recently, new drugs have been introduced having
      less side effects for both the mother and the neonate. METHODS: A literature
      search was undertaken mainly focusing on meta-analyses, to review the possible
      side effects that might affect the course of anaesthesia and to suggest which
      precautions should be considered to prevent the occurrence of significant
      interactions with anaesthetic manipulations and drugs. RESULTS: Magnesium
      sulphate has a proven benefit in lowering systolic blood pressure and preventing
      the occurrence of eclampsia, but not as a tocolytic. beta-adrenergic agonists are
      being abandoned due to the availability of tocolytic agents causing less side
      effects. Calcium channel blockers (CCB) are frequently used but can cause major
      maternal cardiovascular complications. Nitroglycerin seems to be appreciated as
      an acute tocolytic rather than a routine substance during pre-term labour. Cyclo
      oxygenase-2 inhibitors are still under investigation but their tocolytic benefit
      is questionable mainly due to foetal side effects. Atosiban is considered the
      first-choice tocolytic. With respect to oxytocic drugs, oxytocine,
      prostaglandines and methylergometrine may all cause serious side effects
      especially when combined. The cardiovascular side effects of prostaglandins and
      methylergometrine can be life-threatening. Both oxytocin and carbetocin have a
      rather low risk for maternal complications. CONCLUSION: Atosiban and CCB are at
      least as effective tocolytic agents as beta-mimetics but have significantly less
      side effects. Magnesium sulphate can cause neuromuscular blockade, especially
      when combined with CCB. Concerning oxytocic agents, short-acting oxyctocin and
      long-acting carbetocin have the least side effects as compared with
      prostaglandins and methylergometrine.

PMID- 19397507
TI  - The COL9A1 gene is associated with longissimus dorsi muscle area in the pig.

PMID- 19397508
TI  - A proposal for standardization in forensic bovine DNA typing: allele nomenclature
      of 16 cattle-specific short tandem repeat loci.
AB  - In this study, a proposal is presented for the allele nomenclature of 16
      polymorphic short tandem repeat (STR) loci (BM1824, BM2113, ETH10, ETH225,
      INRA023, SPS115, TGLA122, TGLA126, TGLA227, ETH3, TGLA53, BM1818, CSRM60, CSSM66,
      HAUT27 and ILSTS006) for bovine genotyping (Bos taurus). The nomenclature is
      based on sequence data of the polymorphic region(s) of the STR loci as
      recommended by the DNA commission of the International Society of Forensic
      Genetics for human DNA typing. To cover commonly and rarely occurring alleles, a
      selection of animals homozygous for the alleles at these STR loci were analysed
      and subjected to sequence studies. The alleles of the STR loci consisted either
      of simple or compound dinucleotide repeat patterns. Only a limited number of
      alleles with the same fragment size showed different repeat structures. The
      allele designation described here was based on the number of repeats including
      all variable regions within the amplified fragment. The set of 16 STR markers
      should be propagated for the use in all bovine applications including forensic
      analysis.

PMID- 19397509
TI  - Polymorphisms in SPINK5 do not associate with insect bite hypersensitivity in
      Icelandic horses born in Sweden.

PMID- 19397511
TI  - Stearoyl-CoA desaturase 1 genotype and stage of lactation influences milk fatty
      acid composition of Canadian Holstein cows.
AB  - Single nucleotide polymorphisms in the coding region of the bovine stearoyl-CoA
      desaturase 1 gene have been predicted to result in p.293A (alanine at amino acid
      293) and p.293V (valine at amino acid 293) alleles at the stearoyl-CoA
      desaturase1 locus. The objectives of this study were to evaluate the extent to
      which genotypes at the stearoyl-CoA desaturase 1 locus and stage of lactation
      influence milk fatty acid composition in Canadian Holstein cows. Cows with the
      p.293AA genotype had higher C10 index, C12 index and C14 index and higher
      concentrations of C10:1 (10 carbon fatty acid with one double bond), C12:1 (12
      carbon fatty acid with one double bond) and myristoleic acid (C14:1) compared
      with the p.293AV or p.293VV cows. Cows had higher C18 index and total index, and
      lower C10 index, C12 index, C14 index and CLA index during early lactation
      compared with the subsequent lactation stages. Early lactation was also
      characterized by higher concentrations of oleic acid (C18:1 cis-9), vaccenic acid
      (C18:1 trans-11), linoleic acid (C18:2), monounsaturated fatty acids and total
      polyunsaturated fatty acids, and lower concentrations of capric acid (C10:0),
      C10:1, lauric acid (C12:0), C12:1, myristic acid (C14:0), myristoleic acid
      (C14:1), palmitic acid (C16:0) and total saturated fatty acids compared with the
      subsequent lactation stages. Neither the stearoyl-CoA desaturase 1 genotype nor
      the stage of lactation had an influence on conjugated linoleic acid
      concentrations in milk.

PMID- 19397510
TI  - Association analysis between canine behavioural traits and genetic polymorphisms
      in the Shiba Inu breed.
AB  - The relationships between behavioural trait data and the genotype of 15
      polymorphisms in eight neurotransmitter-related genes were analysed in 77 dogs of
      the Shiba Inu breed, an indigenous Japanese dog. The data were obtained from a 26
      item questionnaire on the dog's behaviour, distributed to the dog's owners,
      through veterinary hospitals and the Shiba Inu breed magazine. A factor analysis
      of the questionnaire items extracted eight factors accounting for 66.8% of the
      variance. An association analysis between these factors and genetic polymorphisms
      indicated that the polymorphism of c.471T>C in the solute carrier family 1
      (neuronal/epithelial high-affinity glutamate transporter) member 2 (SLC1A2) gene
      was significantly associated with Factor 1, referred to as 'aggression to
      strangers'. This association remained stable in separate analyses of data from
      surveys obtained from the hospitals and those obtained from the magazine. The
      results suggest that the c.471T>C polymorphism is associated with some types of
      aggressive behaviour in the Shiba Inu. Further studies using other dog breeds are
      necessary to extend these findings to dogs in general.

PMID- 19397512
TI  - Common promoter deletion is associated with 3.9-fold differential transcription
      of ovine CCR5 and reduced proviral level of ovine progressive pneumonia virus.
AB  - Chemokine (C-C motif) Receptor 5 (CCR5) is a chemokine receptor that regulates
      immune cell recruitment in inflammation and serves as a coreceptor for human
      immunodeficiency virus (HIV). A human CCR5 coding deletion (termed delta-32)
      results in strong resistance to HIV infection, and sequence variants in CCR5
      regulatory regions have been implicated in delayed progression to acquired immune
      deficiency syndrome. Both ovine progressive pneumonia virus (OPPV), also known as
      maedi-visna, and HIV are macrophage-tropic lentiviruses, have similar genomic
      structures, and cause lifelong persistent host infection, suggesting CCR5 may
      have a role in regulating OPPV provirus levels. Therefore, the ovine CCR5 genomic
      sequence was determined, and sequence variants were obtained from the open
      reading frame and surrounding regulatory sites. One CCR5 variant contained a 4
      base deletion within a binding site for octamer transcription factors in the
      promoter region. A test for differential transcription from each allele in
      heterozygous animals showed a 3.9-fold transcription difference (P < 0.0001).
      OPPV proviral levels were also measured in 351 naturally exposed Rambouillet,
      Polypay and Columbia sheep. Deletion homozygotes showed reduced OPPV proviral
      levels among these animals (P < 0.01). The association of this CCR5 promoter
      deletion with OPPV levels will need to be validated in additional populations
      before the deletion can be recommended for widespread use in marker-assisted
      selection. However, because of the large impact on transcription and because CCR5
      has roles in inflammation, recruitment of effector cells, and cell-mediated
      immunity, this deletion may play a role in the control of infections of many
      diverse pathogens of sheep.

PMID- 19397513
TI  - Mapping of 12 porcine fatness candidate genes in known fatness QTL based on human
      syntenies.

PMID- 19397514
TI  - Elimination of INPP4A and SLC5A7 as candidate genes for congenital progressive
      ataxia and spastic paresis in pigs.

PMID- 19397515
TI  - Detection of QTL affecting harvest traits in a commercial Atlantic salmon
      population.
AB  - Genetic variation in performance and quality traits measured at harvest has
      previously been demonstrated in Atlantic salmon aquaculture populations. To map
      major loci underlying this variation, we utilized data from 10 families from a
      commercial breeding programme. Significant QTL were detected affecting harvest
      weight and length traits on linkage group 1, and affecting waste weight on
      linkage group 5. In total, 11 of the 29 linkage groups examined showed at least
      suggestive evidence for a QTL. These data suggest that major loci affecting
      economically important harvest characteristics are segregating in commercial
      salmon populations.

PMID- 19397516
TI  - Discovery, characterization and validation of single nucleotide polymorphisms
      within 206 bovine genes that may be considered as candidate genes for beef
      production and quality.
AB  - A large number of putative single nucleotide polymorphisms (SNPs) have been
      identified from the bovine genome-sequencing project. However, few of these have
      been validated and many will turn out to be sequencing artefacts or have low
      minor allele frequencies. In addition, there is little information available on
      SNPs within coding regions, which are likely to be responsible for phenotypic
      variation. Therefore, additional SNP discovery is necessary to identify and
      validate polymorphisms both in specific genes and genome-wide. Sequence-tagged
      sites within 286 genes were resequenced from a panel of animals representing a
      wide range of European cattle breeds. For 80 genes, no polymorphisms were
      identified, and 672 putative SNPs were identified within 206 genes. Fifteen
      European cattle breeds (436 individuals plus available parents) were genotyped
      with these putative SNPs, and 389 SNPs were confirmed to have minor allele
      frequencies above 10%. The genes containing SNPs were localized on chromosomes by
      radiation hybrid mapping and on the bovine genome sequence by Blast. Flanking
      microsatellite loci were identified, to facilitate the alignment of the genes
      containing the SNPs in relation to mapped quantitative trait loci. Of the 672
      putative SNPs discovered in this work, only 11 were found among the validated
      SNPs and 100 were found among the approximately 2.3 million putative SNPs
      currently in dbSNP. The genes studied in this work could be considered as
      candidates for traits associated with beef production and the SNPs reported will
      help to assess the role of the genes in the genetic control of muscle development
      and meat quality. The allele frequency data presented allows the general utility
      of the SNPs to be assessed.

PMID- 19397517
TI  - Fine mapping of quantitative trait loci for mastitis resistance on bovine
      chromosome 11.
AB  - Quantitative trait loci (QTL) affecting clinical mastitis (CM) and somatic cell
      score (SCS) were mapped on bovine chromosome 11. The mapping population consisted
      of 14 grandsire families belonging to three Nordic red cattle breeds: Finnish
      Ayrshire (FA), Swedish Red and White (SRB) and Danish Red. The families had
      previously been shown to segregate for udder health QTL. A total of 524 progeny
      tested bulls were included in the analysis. A linkage map including 33
      microsatellite and five SNP markers was constructed. We performed combined
      linkage disequilibrium and linkage analysis (LDLA) using the whole data set.
      Further analyses were performed for FA and SRB separately to study the origin of
      the identified QTL/haplotype and to examine if it was common in both populations.
      Finally, different two-trait models were fitted. These postulated either a
      pleiotropic QTL affecting both traits; two linked QTL, each affecting one trait;
      or one QTL affecting a single trait. A QTL affecting CM was fine-mapped. In FA, a
      haplotype having a strong association with a high negative effect on mastitis
      resistance was identified. The mapping precision of an earlier detected SCS-QTL
      was not improved by the LDLA analysis because of lack of linkage disequilibrium
      between the markers used and the QTL in the region.

PMID- 19397518
TI  - Genome-wide identification of quantitative trait loci for carcass composition and
      meat quality in a large-scale White Duroc x Chinese Erhualian resource
      population.
AB  - Carcass and meat quality traits are economically important in pigs. In this
      study, 17 carcass composition traits and 23 meat quality traits were recorded in
      1028 F(2) animals from a White Duroc x Erhualian resource population. All pigs in
      this experimental population were genotyped for 194 informative markers covering
      the entire porcine genome. Seventy-seven genome-wide significant quantitative
      trait loci (QTL) for carcass traits and 68 for meat quality were mapped to 34
      genomic regions. These results not only confirmed many previously reported QTL
      but also revealed novel regions associated with the measured traits. For carcass
      traits, the most prominent QTL was identified for carcass length and head weight
      at 57 cM on SSC7, which explained up to 50% of the phenotypic variance and had a
      95% confidence interval of only 3 cM. Moreover, QTL for kidney and spleen weight
      and lengths of cervical vertebrae were reported for the first time in pigs. For
      meat quality traits, two significant QTL on SSC5 and X were identified for both
      intramuscular fat content and marbling score in the longissimus muscle, while
      three significant QTL on SSC1 and SSC9 were found exclusively for IMF. Both LM
      and the semimembranous muscle showed common QTL for colour score on SSC4, 5, 7,
      8, 13 and X and discordant QTL on other chromosomes. White Duroc alleles at a
      majority of QTL detected were favourable for carcass composition, while
      favourable QTL alleles for meat quality originated from both White Duroc and
      Erhualian.

PMID- 19397519
TI  - Whole genome scan to detect quantitative trait loci for bovine milk protein
      composition.
AB  - The objective of this study was to perform a whole genome scan to detect
      quantitative trait loci (QTL) for milk protein composition in 849 Holstein
      Friesian cows originating from seven sires. One morning milk sample was analysed
      for the major milk proteins using capillary zone electrophoresis. A genetic map
      was constructed with 1341 single nucleotide polymorphisms, covering 2829
      centimorgans (cM) and 95% of the cattle genome. The chromosomal regions most
      significantly related to milk protein composition (P(genome) < 0.05) were found
      on Bos taurus autosomes (BTA) 6, 11 and 14. The QTL on BTA6 was found at about 80
      cM, and affected alpha(S1)-casein, alpha(S2)-casein, beta-casein and kappa
      casein. The QTL on BTA11 was found at 124 cM, and affected beta-lactoglobulin,
      and the QTL on BTA14 was found at 0 cM, and affected protein percentage. The
      proportion of phenotypic variance explained by the QTL was 3.6% for beta-casein
      and 7.9% for kappa-casein on BTA6, 28.3% for beta-lactoglobulin on BTA11, and
      8.6% for protein percentage on BTA14. The QTL affecting alpha(S2)-casein on BTA6
      and 17 showed a significant interaction. We investigated the extent to which the
      detected QTL affecting milk protein composition could be explained by known
      polymorphisms in beta-casein, kappa-casein, beta-lactoglobulin and DGAT1 genes.
      Correction for these polymorphisms decreased the proportion of phenotypic
      variance explained by the QTL previously found on BTA6, 11 and 14. Thus, several
      significant QTL affecting milk protein composition were found, of which some QTL
      could partially be explained by polymorphisms in milk protein genes.

PMID- 19397520
TI  - Genetic diversity of Hungarian indigenous chicken breeds based on microsatellite
      markers.
AB  - Six local chicken breeds are registered in Hungary and are regarded as Hungarian
      national treasures: Hungarian White, Yellow and Speckled, and Transylvanian Naked
      Neck White, Black and Speckled. Three Hungarian academic institutes have
      maintained these genetic resources for more than 30 years. The Hungarian Yellow,
      the Hungarian Speckled and the Transylvanian Naked Neck Speckled breeds were kept
      as duplicates in two separate subpopulations since time of formation of
      conservation flocks at different institutes. In this study, we investigated
      genetic diversity of these nine Hungarian chicken populations using 29
      microsatellite markers. We assessed degree of polymorphism and relationships
      within and between Hungarian breeds on the basis of molecular markers, and
      compared the Hungarian chicken populations with commercial lines and European
      local breeds. In total, 168 alleles were observed in the nine Hungarian
      populations. The F(ST) estimate indicated that about 22% of the total variation
      originated from variation between the Hungarian breeds. Clustering using
      structure software showed clear separation between the Hungarian populations. The
      most frequent solutions were found at K = 5 and K = 6, respectively, classifying
      the Transylvanian Naked Neck breeds as a separate group of populations. To
      identify genetic resources unique to Hungary, marker estimated kinships were
      estimated and a safe set analysis was performed. We show that the contribution of
      all Hungarian breeds together to the total diversity of a given set of
      populations was lower when added to the commercial lines than when added to the
      European set of breeds.

PMID- 19397521
TI  - A radiation hybrid comparative map of ovine chromosome 1 aligned to the virtual
      sheep genome.
AB  - Ovis aries chromosome one (OAR1) is the largest submetacentric chromosome in the
      sheep genome and is homologous to regions on human chromosomes 1, 2, 3 and 21.
      Using the USUoRH5000 ovine whole-genome radiation hybrid (RH) panel, we have
      constructed a RH map of OAR1 comprising 102 framework and 75 placed/binned
      markers across five linkage groups spanning 3759.43 cR5000, with an average
      marker density of 21.2 cR5000/marker. The alignment of our OAR1 RH map shows good
      concordance with the recently developed virtual sheep genome, with fewer than
      1.86% discrepancies. A comparative map of OAR1 was constructed by examining the
      location of RH-mapped orthologues in sheep within the genomes of cow, human,
      horse and dog. Analysis of the comparative map indicates that conserved syntenies
      within the five ovine RH linkage groups underwent internal chromosomal
      rearrangements which, in general, reflect the evolutionary distances between
      sheep and each of these four species. The ovine RH map presented here integrates
      all available mapping data and includes new genomic information for ovine
      chromosome 1.

PMID- 19397522
TI  - Quantitative trait loci underlying milk production traits in sheep.
AB  - Improvement of milk production traits in dairy sheep is required to increase the
      competitiveness of the industry and to maintain the production of high quality
      cheese in regions of Mediterranean countries with less favourable conditions.
      Additional improvement over classical selection could be reached if genes with
      significant effects on the relevant traits were specifically targeted by
      selection. However, so far, few studies have been undertaken to detect
      quantitative trait loci (QTL) in dairy sheep. In this study, we present a
      complete genome scan performed in a commercial population of Spanish Churra sheep
      to identify chromosomal regions associated with phenotypic variation observed in
      milk production traits. Eleven half-sib families, including a total of 1213 ewes,
      were analysed following a daughter design. Genome-wise multi-marker regression
      analysis revealed a genome-wise significant QTL for milk protein percentage on
      chromosome 3. Eight other regions, localized on chromosomes 1, 2, 20, 23 and 25,
      showed suggestive significant linkage associations with some of the analysed
      traits. To our knowledge, this study represents the first complete genome scan
      for milk production traits reported in dairy sheep. The experiment described here
      shows that analysis of commercial dairy sheep populations has the potential to
      increase our understanding of the genetic determinants of complex production
      related traits.

PMID- 19397523
TI  - PRNP haplotype distribution in Moroccan goats.
AB  - Susceptibility/resistance to scrapie in sheep and goats is influenced by host
      prion protein gene (PRNP) genotype. In this study, we report the analysis of
      prion protein gene polymorphisms in 137 goats of two Moroccan populations: D'man
      and Chaouni. We found seven previously described amino acid polymorphisms at
      codons 37, 127, 137, 142, 154, 222 and 240, as well as three known silent
      mutations. In addition, we identified three new allelic variants: 101R and 139S
      in D'man goats and 145D in D'man and Chaouni individuals. The high frequency of
      the resistant allele 154H could offer genetic protection against the disease to
      the analysed animals. A total of 12 haplotypes and 28 genotypes were found, the
      distribution of which shows significant differences between both groups.
      Moreover, haplotype frequencies were compared with bibliographic data showing
      that the haplotype distribution of PRNP in Moroccan populations is genetically
      similar to Southern Italian and Greek goats.

PMID- 19397524
TI  - Genomic structure, chromosomal localization and expression profile of a porcine
      long non-coding RNA isolated from long SAGE libraries.
AB  - Long non-coding RNA (long ncRNA) is a novel class of ncRNA that may be involved
      in critical cellular processes. A considerable number of mammalian long ncRNAs
      have now been isolated but only a small number of these nucleic acids have been
      functionally well characterized. In this study, to determine the structure,
      regulation and function of long ncRNA in pigs, TncRNA was isolated from this
      mammal and its potential function during pig foetus development was identified.
      We anticipated that this would provide new insights into functional genomic
      studies in the pig. Using LongSAGE libraries generated from Chinese indigenous
      Tongcheng and Landrace pigs at three prenatal stages, a novel porcine long ncRNA
      was identified, TncRNA, which was found to be differentially expressed during
      myogenesis. The full-length cDNA for this gene is 3409 bp, and it harbours a
      typical polyadenylation signal sequence located 18 bp upstream from the 3' poly
      (A) tail. Genomic sequence analysis showed that pig TncRNA is alternatively
      spliced and several transcripts were detected. Using the INRA-University of
      Minnesota porcine radiation hybrid panel, TncRNA was assigned to SSC2 and found
      to be closely linked to the microsatellite marker SW256. Porcine TncRNA was found
      to be expressed in all tissues examined but in variable amounts. Comparisons
      between the expression profiles of TncRNA at different development stages in
      Tongcheng and Landrace pigs revealed up-regulation of this molecule in prenatal
      skeletal muscle, and differential expression in 90-day-old foetal skeletal muscle
      between these two pig breeds. This is the first report to describe a long ncRNA
      in pig. Moreover, the distinct expression pattern and structure of porcine TncRNA
      suggest that it performs complex and critical functions during foetal
      development.

PMID- 19397525
TI  - The population genetic effects of ancestry and admixture in a subdivided cattle
      breed.
AB  - The genetic structure of the Dexter, a minority cattle breed with complex
      demographic history, was investigated using microsatellite markers and a range of
      statistical approaches designed to detect both admixture and genetic drift.
      Modern representatives of two putative ancestral populations, the Devon and
      Kerry, together with the different populations of the Dexter, which have
      experienced different demographic histories, were analysed. Breed units showed
      comparatively high levels of genetic variability (H(E) = 0.63-0.68); however,
      distinct genetic subgroups were detected within the Dexter, which could be
      attributed to known demographic events. Much lower diversity was identified in
      three small, isolated Dexter populations (H(E) = 0.52-0.55) and higher
      differentiation (F(ST) > 0.13) was found. For one of these populations, where
      strong selection has taken place, we also found evidence of a demographic
      bottleneck. Three methods for quantifying breed admixture were applied and
      substantial method-based variation in estimates for the genetic contribution of
      the two proposed ancestral populations for each subdivision of the Dexter was
      found. Results were consistent only in the case of a group consisting of selected
      Traditional Dexter animals, where the ancestor of the modern Kerry breed was also
      determined as the greater parental contributor to the Dexter. The inconsistency
      of estimation of admixture proportions between the methods highlights the
      potentially confounding role of genetic drift in shaping small population
      structure, and the consequences of accurately describing population histories
      from contemporary genetic data.

PMID- 19397526
TI  - Variation in mitochondrial DNA and maternal genetic ancestry of Ethiopian cattle
      populations.
AB  - This study describes complete control region sequences of mitochondrial DNA
      (mtDNA) from 117 Ethiopian cattle from 10 representative populations, in
      conjunction with the available cattle sequences in GenBank. In total, 79
      polymorphic sites were detected, and these defined 81 different haplotypes. The
      haplotype and nucleotide diversity of Ethiopian cattle did not vary among the
      populations studied. All mtDNA sequences from Ethiopian cattle converged into one
      main maternal lineage (T1) that corresponds to African Bos taurus cattle.
      According to the results of this study, no zebu mtDNA haplotypes have been found
      in Ethiopia, where the most extensive hybridization took place on the African
      continent.

PMID- 19397527
TI  - Linkage confirms canine pkd1 orthologue as a candidate for bull terrier
      polycystic kidney disease.
AB  - Bull terrier polycystic kidney disease (BTPKD) is a Mendelian disorder with many
      features reminiscent of human autosomal dominant polycystic disease, the latter
      disease being due to mutations at PKD1 and PKD2 loci. We investigated the role of
      the canine pkd1 orthologue in BTPKD via linkage analysis of a large kindred in
      which the disorder is segregating. Twelve microsatellite markers around the
      canine pkd1 locus (CFA6) were amplified from the genomic DNA of 20 affected and
      16 unaffected bull terriers. An additional 28 affected dogs were genotyped at
      five key microsatellites. A highly significant multi-point LOD score that peaked
      over the canine pkd1 locus was observed (LOD = 6.59, best two-point LOD score LOD
      = 6.02), implicating this as the BTPKD locus.

PMID- 19397528
TI  - Detailed characterization of the porcine MC4R gene in relation to fatness and
      growth.
AB  - In contrast to the human MC4R gene, where multiple variants have been described,
      several of which are associated with appetite and obesity, few MC4R variants have
      been reported in the pig. The most interesting polymorphism reported to date in
      the pig is p.Asp298Asn, which is significantly associated with variation in
      growth and fatness traits in most breeds and crosses. However, some reports have
      seemingly failed to confirm this association. The discrepancy of p.Asp298Asn
      associations in some pig populations suggested that further discovery of SNPs in
      MC4R would be useful. Utilizing the recently released pig genome sequence
      information, we obtained the whole MC4R genome sequence and detected five
      additional SNPs, a variable (CA)(n) repeat and a C indel in the ISU Berkshire x
      Yorkshire pig resource family. Linkage disequilibrium (LD) analysis revealed that
      the additional five SNPs were not in strong LD with p.Asp298Asn, but single
      marker association analysis indicated that they were significantly (P < 0.05)
      associated with fatness measures and very highly significantly (P < 0.0001)
      associated with average daily gain on test (ADGTEST). Three major haplotypes were
      identified and the subsequent association analyses suggested that the two non
      synonymous SNPs had different effects, e.g. p.Arg236His influenced back fat and
      growth on test while p.Asp298Asn was primarily associated with variation in
      growth rate in this population. An interaction effect between these two SNPs was
      found for ADGTEST, which may partly explain some of the previous discrepancies
      reported for MC4R in different pig populations. Examination of the p.Arg236His
      polymorphism in populations where the effect of p.Asp298Asn is limited is
      warranted.

PMID- 19397529
TI  - Motor performance in very preterm infants before and after implementation of the
      newborn individualized developmental care and assessment programme in a neonatal
      intensive care unit.
AB  - AIM: To compare motor performance in supine position at the age of 4-months
      corrected age (CA) in very preterm (VPT) infants cared for in a neonatal
      intensive care unit (NICU) before and after the implementation of the Newborn
      Individualized Developmental Care and Assessment Program (NIDCAP). METHODS:
      Assessments of motor performance in supine position according to level of motor
      development and quality of motor performance were made, using the Structured
      Observation of Motor Performance in Infants (SOMP-I). SUBJECTS: VPT infants cared
      for in a NICU at a Swedish university hospital before, Group A (n = 68), and
      after, Group B (n = 58), the implementation of developmentally supportive care
      based on NIDCAP. RESULTS: The infants who were treated after the introduction of
      NIDCAP showed higher level of motor development in the arms/hands and trunk. No
      significant group differences were noted in total deviation score for the
      respective limbs, but lower frequency of lateral flexion in head movements,
      extension-external rotation-abduction, extension-internal rotation-adduction and
      varus and valgus position in the feet was found in the NIDCAP group, compared
      with those treated before the introduction. CONCLUSION: The infants who were
      treated after NIDCAP care had been implemented showed a higher level of motor
      development in arms/hand and trunk and fewer deviations in head, legs and feet at
      4-months CA than infants treated before NIDCAP implementation. The observed
      changes may be due to NIDCAP and/or improved perinatal and neonatal care during
      the studied time period.

PMID- 19397530
TI  - The pattern of self-poisoning among Lebanese children and adolescents in two
      tertiary care centres in Lebanon.
AB  - AIM: Self-poisoning in childhood and adolescence is a major problem for health
      authorities all over the world. The objective of this study was to determine the
      pattern of self-poisoning in Lebanese children and adolescents. MATERIALS AND
      METHODS: This prospective study included all cases of poisoning in individuals
      aged 0-18 years who presented to the emergency department of two major hospitals
      in Beirut, Lebanon over a period of 1 year. Participants were divided into two
      age groups (0-12 years and 12-18 years). These cases were followed to record the
      applied treatment and whether the patient was admitted or discharged. RESULTS:
      There were 110 self-poisoning incidents, of which 74 (67%) were in female
      patients. The predominant type of poisoning was with pharmaceutical products
      (68.2%). Accidental self-poisoning was significantly more common in the younger
      age group among both genders compared with the older age group (p < 0.0001).
      There were significantly more poisoned male children (72%) than male adolescents
      (28%) (p = 0.003); whereas among females, poisoned adolescents were significantly
      more common (64%) than poisoned children (36%) (p = 0.009). Moreover, poisoning
      with pharmaceuticals was significantly higher in the young male group compared to
      the older age group and older female group compared to the younger age group (p =
      0.0007 and p = 0.01, respectively). In total, 78% of patients were discharged
      home following basic observation, charcoal or gastric lavage. CONCLUSION: Female
      adolescents are more at risk of deliberate self-intoxication after the age of 12
      years compared to males, whereas males younger than 12 years are more likely to
      suffer from accidental poisoning. Preventative strategies include screening
      adolescents at high risk of self-harm in order to offer adequate counselling,
      while providing anticipatory guidance for parents of children in the younger age
      group.

PMID- 19397531
TI  - Genetic polymorphisms in Thai neonates with hyperbilirubinemia.
AB  - AIM: Polymorphisms of the UGT1A1 gene, SLCO1B1 gene and GST gene have been
      associated with significant hyperbilirubinemia. We would like to determine
      whether the variation of UGT1A1 gene, SLCO1B1 gene and GST gene may play a
      significant role in neonatal hyperbilirubinemia in Thai infants. METHODS: Ninety
      one study subjects (hyperbilirubinemic group) and 86 control subjects were
      studied. RESULTS: The cause of neonatal hyperbilirubinemia could not be
      identified in 64 infants (70.3%), ABO blood group incompatibility in 14.3% and
      Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 8.8%. In the
      hyperbilirubinemic group, 23 of 91 (25.3%) infants demonstrated variant of UGT1A1
      at nucleotides (nt) 211 as compared to 6 of 86 (7%) in the control group (p =
      0.001). There were no significant differences between groups in the variants
      UGT1A1 at nt 686, SLCO1B1 gene at nt 388, 463 and the GST gene. Male infants with
      G-6-PD deficiency were associated with hyperbilirubinemia (21.2% vs. 4.8% in the
      control group) with an odds ratio (OR) of 5.37 (p = 0.02). The relationship
      between G-6-PD and variant in UGT1A1 gene at nt 211 could not be determined.
      CONCLUSION: Thai infants with variant in the UGT1A1 at nt 211 or with G-6-PD
      deficiency are at higher risk for developing neonatal hyperbilirubinemia.

PMID- 19397532
TI  - Predicting health-related quality of life of parents of children with inherited
      metabolic diseases.
AB  - AIM: The aim of this study was to examine medical, socio-demographic and
      psychosocial determinants of health-related quality of life (HRQoL) of parents of
      children with metabolic diseases. METHODS: A survey among parents of children
      with metabolic diseases (children aged 1-19 years, diagnosed >1 year before the
      start of the study, living at home). Parents were approached through the Emma
      Children's Hospital, and through a national parent and patient association. HRQoL
      was assessed using the TNO-AZL Questionnaire for Adult's Health Related Quality
      of Life (TAAQOL), describing 12 domains of HRQoL. Predictor variables were taken
      from a self-report questionnaire. Univariate and multivariate logistic regression
      analyses were performed to predict which parents were at risk for HRQoL
      impairment. RESULTS: Mainly psychosocial determinants were predictive for
      parental HRQoL. Emotional support was protective for parental HRQOL while loss of
      friendship was a risk factor for HRQoL impairment. Medical and socio-demographic
      variables did not consistently predict parental HRQoL. CONCLUSION: Psychosocial
      determinants appeared more important in predicting parental HRQoL than medical
      and socio-demographic variables. Interventions should be focused on supporting
      parents combining the care for their children with a social life. Further
      research on this subject is necessary. In the meantime, involved medical
      specialists should pay structural attention to parental functioning.

PMID- 19397533
TI  - Natural evolution of regurgitation in healthy infants.
AB  - OBJECTIVES: To determine the natural history of infant regurgitation during the
      first year of life. METHODS: Parents recorded prospectively the frequency of
      regurgitation for 1 week before consultation during the first year of life. A sub
      group analysis according to the method of feeding was planned. RESULTS: A total
      of 130 infants of an original sample of 163 (80%) newborns were followed up for 1
      year. Daily spilling was highest during the first month of life (73%) and
      decreased gradually to 50% during the fifth month of life. During the first 2
      months of life, 20% of the infants regurgitated more than four times per day.
      After the age of 12 months, only 4% of the infants had daily regurgitations.
      Exclusively breastfed infants did regurgitate less than partially breastfed
      infants. Weight gain was influenced by the frequency of regurgitation, especially
      in partially breastfed infants. CONCLUSION: Regurgitation in infancy is common,
      decreasing from birth, and tends to disappear by 12 months of age. Weight gain
      during the first 4 months of life is decreased in infants who regurgitate more
      than four times a day. Our data suggest that exclusively breastfed infants
      regurgitate less than partially breastfed babies.

PMID- 19397534
TI  - alpha-Adrenoceptor agonists for the treatment of vasovagal syncope: a meta
      analysis of worldwide published data.
AB  - AIM: The present study was aimed at evaluating present randomized controlled
      trials (RCTs) regarding the effect of alpha-adrenoceptor agonists on vasovagal
      syncope (VVS). METHODS: According to inclusion and exclusion criteria, articles
      were selected from medical electronic databases. RCTs were then assessed based on
      the Juni assessment, and meta-analysis was completed using the Review Manager 4.2
      software. Indication to further evaluate effects was the recurrence of syncope
      during follow-up treatment or a response in the head-up tilt test (HUT) after
      treatment. The results were stated as odd ratio (OR), with a 95% confidence
      interval (CI) and a p < 0.05 significant level. RESULTS: In total, six RCTs were
      selected. Funnel plot analysis showed possible publication bias. Meta-analysis of
      the six RCTs, including all 165 patients in the treatment group and 164 patients
      in the control group, indicated that alpha-adrenoceptor agonists were more
      effective than placebos in treating VVS (OR = 0.21, 95% CI: 0.06-0.77, p = 0.02).
      The further, weighted independent t-test disclosed that the weighted mean
      percentage of responders for midodrine (76.3%+/- 7.7%) was significantly higher
      than that for etilefrine (65.5%+/- 15.4%) (t = 5.863, p < 0.001). CONCLUSION: The
      currently published RCTs support that alpha-adrenoceptor agonists might be
      effective for VVS. Midodrine can be regarded as a better choice compared with
      etilefrine.

PMID- 19397535
TI  - A comparative study of sanitary napkins and absorbent nappy pads for urine output
      measurement in neonates.
AB  - AIM: To compare sanitary napkins and absorbent nappy pads (ANP) for urine output
      (UO) measurement. METHODS: Phase 1: Freshly passed neonatal urine (5, 10 and 15
      mL) was poured onto preweighed sanitary napkins or ANP, which were juxtaposed to
      the genital area of manikins placed in incubators/warmers and weighed at (1/2),
      1, 2, 4, 5 and 6 hr. Outcome was percentage weight change from baseline. Phase 2:
      Five very low birth weight boys in incubators had UO measurement by test tubes. A
      sanitary napkin or ANP was co-applied with the test tube for 4 h each. Urine
      collected in the test tube was measured and poured on the device, which was
      reapplied. Weight and wetness were checked. RESULTS: Phase 1: Mean urine loss was
      8.35, 13.8, 20.1, 25.2, 33.1, 38.7 and 42.6% at (1/2), 1, 2, 3, 4, 5 and 6 h,
      respectively (repeated measures ANOVA [RM-ANOVA], p < 0.001). Loss was higher
      with ANP than sanitary napkins (32.1% vs. 13.4%, two-way RM-ANOVA, p = 0.001).
      There was less loss in incubators versus radiant warmers at 6 h (p = 0.09). Phase
      2: There was 12.1 and 26% deficit with sanitary napkin and ANP, respectively.
      Wetness was felt in one and four cases, respectively. CONCLUSION: Urinary losses
      are less from sanitary napkins than ANPs.

PMID- 19397536
TI  - Playing a violent television game does not affect saliva cortisol.

PMID- 19397538
TI  - Labour increases the surface expression of two Toll-like receptors in the cord
      blood monocytes of healthy term newborns.
AB  - AIM: Mode of delivery may influence the innate immune system in newborns. We
      investigated the effect of maternal labour on the expression of two Toll-like
      receptors, TLR2 and TLR4, in monocytes obtained from healthy full-term newborns.
      METHODS: Monocytes were obtained from cord blood of 48 newborns that have been
      vaginally delivered (VD) and 14 newborns delivered by elective caesarean section
      (CS) without labour. Peripheral blood was also obtained from 17 healthy adults.
      Surface expression of TLR2 and TLR4 in the monocytes was measured by antihuman
      TLR2 or TLR4 monoclonal antibody and immunofluorescence flow cytometry. TLR2 and
      TLR4 mRNA levels were evaluated by real-time PCR. RESULTS: CS newborns had a
      significantly lower level of TLR2 and TLR4 surface expression on monocytes than
      VD newborns. No significant difference was found between the surface expression
      of VD newborns and healthy adults. TLR2 and TLR4 mRNA levels in monocytes did not
      vary among the three study groups. CONCLUSION: Labour may up-regulate TLR2 and
      TLR4 on the cord blood monocytes of newborns at the protein level. Since TLRs are
      an important part of the innate immune system, our findings suggest that labour
      may be immunologically beneficial to normal newborns.

PMID- 19397539
TI  - Glucose infusions into peripheral veins in the management of neonatal
      hypoglycemia--20% instead of 15%?
AB  - AIM: To establish whether peripheral intravenous 20% glucose solutions would
      cause less local irritation, fewer cannulation changes and less weight gain than
      15% glucose in newborn infants. METHODS: A total of 121 newborn infants with
      hypoglycemia were randomized to receive either 20% (group 20%, 60 infants) or 15%
      (group 15%, 61 infants) glucose infusions, which were initiated at 8 mg/kg/min
      rates and tapered according to the blood glucose levels. When the cannulation
      site had to be changed, signs of phlebitis at the previous cannulation site were
      scored (0-3). Number of cannulation site changes, durations of infusions and the
      infants' daily weights were recorded. RESULTS: The median durations of infusions
      in groups 20 and 15% were 4 (range 2-7) days versus 4 (range 2-8) days and the
      median number of cannulation site changes were 1 (range 0-6) versus 1 (range 0
      5), respectively. Thirty-six infants in group 20% and 37 in group 15% developed
      some phlebitis, median severity scores being 1 (range 0-7) versus 15% 1 (range 0
      8). The weights during the treatment were also similar. CONCLUSION: 20% and 15%
      glucose solutions can be infused equally safely into peripheral veins in
      neonates.

PMID- 19397540
TI  - Big snake, small snake: which wound is worse when bitten?
AB  - Snakebites in children and teenagers are relatively uncommon in the metropolitan
      city of Hong Kong. They are rarely fatal but may cause significant morbidity and
      fear. We report two cases of snakebites to illustrate that the spectrum of
      morbidity is independent of the size of the snakes. A 7-year-old boy was bitten
      in successions by a green snake. Envenomation occurred at the second bite site.
      He developed local and systemic signs that were promptly relieved with anti-venom
      therapy at the intensive care unit. An 18-year-old girl was bitten by a large
      python but only sustained minor local soft tissue injuries. This report serves to
      alert the public that snake may bite in successions and envenomation may occur
      with the subsequent bite. CONCLUSION: A small snake may be venomous and a large
      snake may not be. Avoidable risk factors associated with snakebites (such as
      avoiding areas known to harbour snakes in the evening in summer and autumn and
      wearing protective footwear) are highlighted.

PMID- 19397541
TI  - Once daily dose gentamicin in neonates - is our dosing correct?
AB  - AIM: The aim of this paper is to study the safety and efficacy (measured by
      therapeutic level) of once daily gentamicin in neonates >or=32 weeks of gestation
      and <or=7 days of age. SETTING: Level II neonatal intensive care unit. SUBJECTS:
      Neonates >or=32 weeks of gestation and <or=7 days of age treated with gentamicin
      for presumed sepsis. METHODS: Gentamicin was administered by intravenous
      injection at 4 mg/kg/day once daily. Peak and trough gentamicin levels were
      measured at the third dose. RESULTS: In neonates with gestational age between 32
      and 36 weeks, 14 out of 65 (22%) had trough serum concentration >2 mg/L. Only 39
      (60%) had peak and trough levels within the therapeutic range. All babies who had
      audiometric evaluation (62 out of 65) had normal hearing. Out of the 65 babies,
      60 had paired serum creatinine levels estimated and none had evidence of renal
      dysfunction. Among term neonates, only 2 out of 50 had the trough serum
      concentration of >2 mg/L. In 38 (76%) of the 50 neonates, the trough serum
      gentamicin concentration was <2.0 mg/L and the peak level was <10 mg/L. Forty
      eight babies had audiometric evaluation which was normal. CONCLUSION: A dose of 4
      mg/kg/day produces serum gentamicin levels outside the therapeutic range in two
      fifths of neonates between 32 and 36 +/- 6 weeks. A single dose of 4 mg/kg/day of
      gentamicin is appropriate for term babies and probably excessive for 32-36 weeks'
      neonates.

PMID- 19397542
TI  - Antibiotic usage, dosage and course length in children between 0 and 4 years.
AB  - AIM: Antibiotic drugs are most frequently used by 0- to 4-year-old children. We
      performed a cross-sectional study in the Netherlands using a pharmacy
      prescription database to investigate the use, dose and course length of
      antibiotic drugs in 0- to 4-year-olds. METHODS: We used a database with pharmacy
      drug-dispensing data. We investigated all prescriptions of systemic antibiotics
      prescribed in the years 2002-2006 for children of 0-4 years of age. Prescriptions
      for children under the age of 3 months were excluded. RESULTS: Children of 9-12
      months of age received more antibiotics than children in other age groups. In the
      3- to 6-month-olds, amoxicillin was prescribed in 75.2% of the cases. This
      percentage was 50.4% in the 4-year-olds. The contribution of other broad-spectrum
      antibiotics increased with age (clarithromycin and amoxicillin/clavulanic acid).
      Small-spectrum penicillins were prescribed less often than the broad-spectrum
      antibiotics. From the prescriptions of the five most used drugs, 97.6% were
      within the recommended dose range. Most course lengths corresponded with the
      guidelines. Of the prescriptions, 3.9% were unlicensed or off-label. CONCLUSION:
      Within the group of 0- to 4-year-old children, most antibiotics were used by 9-
      to 12-month-olds. The doses and course lengths were mostly correct, but the
      choice of antibiotics was not according to the guidelines. Young children
      received unlicensed and off-label prescribed antibiotics.

PMID- 19397543
TI  - Prejudice against obesity among 10-year-olds: a nationwide population-based
      study.
AB  - AIMS: Population-based research on children's possible prejudice against thin,
      obese and average body sizes is scarce. This study examined children's prejudice
      against various body sizes of both sexes. The effects of sex, body size, place of
      residence and socio-economic status (SES) on children's prejudice were also
      investigated. METHODS: In 2005, a nationally representative sample of 10-year-old
      children (N = 1409) responded to a questionnaire measuring stereotypes and
      prejudice against thin, average-weight and obese silhouettes. RESULTS: As
      estimated by odds ratios (ORs), children were more likely to report prejudice
      against obesity (OR = 53, 95% confidence interval [CI]: 42-67) and thinness (OR =
      20, 95% CI: 16-26) than against average body weight. The risk of being prejudiced
      varied with child's sex and with sex and body size of the silhouette figure. No
      association was found between own body weight and prejudice against various body
      sizes. Children with high SES were more likely to be prejudiced against obesity
      compared with children with low SES (OR = 1.2, 95% CI: 1.1-1.4). CONCLUSION: This
      large, population-based study showed that Swedish 10-year-old children hold
      stereotypical attitudes and are prejudiced against not only peers with obesity
      but also those with thin body sizes. Interestingly, no association was found
      between own body weight and prejudice against various body sizes.

PMID- 19397545
TI  - Age-related changes in BAER at different click rates from neonates to adults.
AB  - AIM: To characterize age-related changes in brainstem auditory evoked response
      (BAER) at different click rates from neonates to adults. METHODS: BAER was
      studied at repetition rates 11-91/sec of clicks in 165 normal neonates and
      children of various ages and 29 young adults. RESULTS: BAER wave latencies and
      inter-peak intervals increased linearly with increasing click rate at all ages.
      The younger was the age, the greater were BAER click rate-dependent changes. At 9
      months and younger, the slopes of latency- and interval-rate functions were all
      significantly greater than in the adults (all p < 0.01). The slopes of wave I
      latency- and I-III interval-rate functions at 1-2 years and older were similar to
      those in adults. The slopes of wave III and V latency-rate functions and I-V and
      III-V interval-rate function at 3-4 years and older did not differ significantly
      from those in adults. CONCLUSION: BAER is affected by stimulus rate more in
      younger children than in the older. Adult-like rate-dependent changes are reached
      at 1-2 years for wave I latency and I-III interval, and 3-4 years for wave III
      and V latencies and I-V and III-V intervals. Our BAER data at different click
      rates provide normal references for subjects of various ages.

PMID- 19397546
TI  - Allergic rhinitis: more than just a stuffy nose.
AB  - Allergic rhinitis is more than just sneezing and an itchy nose. Complications of
      this disease are numerous and can have a significant impact, both mentally and
      physically. That is why it is important not only to detect, investigate and treat
      allergic rhinitis but also to actively identify potential complications. Mental
      functions such as learning, sleep and activity levels can deteriorate, and the
      eustachian tubes, sinuses and airway functions can be affected. Otitis, sinusitis
      and asthma are overrepresented among individuals who suffer from allergic
      rhinitis. This article highlights how allergic rhinitis can affect cognitive
      functions, and what consequences this can have on school performance, work and
      quality of life. CONCLUSION: Health professionals and school personnel need to
      increase their awareness of the ramifications of this disease and actively work
      to prevent deterioration in both academic achievement and workplace productivity.

PMID- 19397547
TI  - Orofacial granulomatosis in childhood-a clinical entity that may indicate Crohn's
      disease as well as food allergy.
AB  - AIM: Orofacial granulomatosis (OFG) is a rare clinical entity with orofacial
      swelling in association with oral lesions such as mucosal oedema, ulcerations and
      mucosal tags. The aim of this prospective study was to evaluate the connection
      between OFG in childhood and systemic disease. METHODS: During a 3-year period,
      eight children (9-16 years old) who had been referred to the clinic of oral
      medicine were diagnosed solely with OFG. Thus, none of them had any known
      systemic disease or gastrointestinal symptoms at the time of referral. The
      children were then medically examined and followed up for 6-8 years at the
      department of paediatrics for systemic disease with specific emphasis on
      inflammatory disorders elsewhere in the gastrointestinal tract. RESULTS: During
      follow-up, four patients were diagnosed with Crohn's disease (CD). Further, one
      girl was found to have a food allergy-induced OFG, with delayed-type
      hypersensitivity to oats. One boy developed both diabetes and celiac disease
      during the follow-up. Only two patients had no diagnosis of systemic disease at
      the end of the observation period. CONCLUSION: OFG in childhood seems to be
      frequently related to systemic disease, and children with OFG should be referred
      to a paediatrician for examination and follow-up.

PMID- 19397549
TI  - Urban paediatric trauma due to stab wounds: an Israeli hospital experience.
AB  - OBJECTIVE: To assess the incidence and types of stab wounds to hospitalized
      children and adolescents. SUBJECTS: The sample consisted of patients, age 6-18
      years, who were admitted to our hospital with sustained injury between 1991 and
      2007. RESULTS: In total, 83 patients were admitted as a result of penetrating (n
      = 51) and superficial (n = 32) injuries. Eighty-two were hospitalized, and one
      was declared dead upon arrival. Only 11 patients were hospitalized during the
      1991-2000 period, and 71 during the 2001-2007 period. Ten patients were admitted
      to the intensive care unit (ICU); 23 patients were operated (hospital mortality =
      0). Evacuation time (time from injury to hospital) was 10 min (mean time; maximum
      35 min). CONCLUSION: This study found higher rates of hospitalization compared
      with those over a decade ago. These rates reflect not only changes in
      hospitalization trends and/or population growth in the hospital area but also an
      increase of urban violence. Israeli hospitalization system deals with paediatric
      trauma effectively, being well trained because of permanent terrorist activity.

PMID- 19397550
TI  - Motor performance in 5-year-old preschool children with developmental speech and
      language disorders.
AB  - AIM: The aim of the study was to evaluate motor performance in 5-year-old
      children with mild-to-moderate developmental speech and language disorders (DSLD)
      in comparison of age- and gender-matched healthy children. MATERIALS AND METHODS:
      A total of 32 DSLD children and 45 control group (CG) children participated in
      our study. The children were examined for dexterity skills and gross motor
      function through vertical jumping performance, maximal isometric strength of the
      leg extensors and isometric hand-grip strength. RESULTS: Dexterity skills did not
      differ significantly in the measured groups, but DSLD children performed more
      poorly in gross motor tasks. DSLD children demonstrated significantly lower
      vertical jumping height compared to CG children. DSLD girls had lower isometric
      strength of the leg extensors compared to all other measured groups. The hand
      grip strength was greater in CG boys compared to all other measured groups. No
      significant differences in this parameter were observed between CG girls and DSLD
      children, although DSLD girls' result was the lowest. CONCLUSION: In children
      with mild-to-moderate DSLD, the lag of gross motor development is clearly
      evident; however, they do not differ from CG children in dexterity skills. DSLD
      girls had more affected gross motor function compared to DSLD boys.

PMID- 19397551
TI  - Suspected infections in children treated for ALL.
AB  - AIM: The aim of our study was to get epidemiological information on bacterial
      infections in children treated for ALL and to analyse which patients have an
      enhanced infection risk. METHODS: Episodes of suspected or confirmed infections
      were evaluated during the first 12 months of treatment for childhood acute
      lymphoblastic leukaemia (ALL). RESULTS: The number of patients was 73 (43 boys).
      The median age was 4.6 years. A total of 179 episodes occurred, varying from none
      in six patients to eight in one. Bacteria were cultured in 57 episodes (31.8%),
      the most common being coagulase-negative staphylococci. The number of episodes
      fell significantly with increasing age for suspected and confirmed infections (p
      < 0.001 and p = 0.03). The proportion of confirmed infections was significantly
      higher (p < 0.001) in the first episodes. The average number of suspected
      infections was higher in girls than in boys (p = 0.03), but confirmed infections
      were not. CONCLUSION: Most of the serious infections occur early in the treatment
      and the number of suspected and confirmed infections falls with age. Suspicion of
      infection is more likely in girls, but the number of confirmed infections is
      equal in both sexes. Coagulase-negative staphylococcus was most commonly
      isolated, highlighting the importance of careful handling of central venous
      devices.

PMID- 19397552
TI  - Cardiorespiratory measures before and after feeding challenge in term infants are
      related to birth weight.
AB  - AIM: This study tested the hypothesis that, within a few hours of delivery,
      cardiorespiratory measure taken during feeding provides markers of group
      differences related to birth weight. A secondary hypothesis was that high
      frequency heart period variability would be related to underlying differences in
      autonomic control associated with birth weight. METHODS AND SUBJECTS: One hundred
      four term infants in the lowest, middle, and highest birth weight quintiles were
      enrolled. Exclusion criteria were evidence of drug abuse, congenital anomalies,
      Apgar scores less than 7 or admission to the neonatal intensive care unit. Within
      96 h of delivery, heart and respiratory rates, blood pressures and heart period
      variability were measured before, during and after feeding. RESULTS: Term babies
      in the lowest quintile of birth weights have lower heart rates prior to feeding
      but greater increases in heart rate during the early postprandial period.
      Assessments of high-frequency heart period variability suggest that small term
      infants have greater parasympathetic tone before feeding and more sustained
      parasympathetic withdrawal following feeding. CONCLUSION: Measurements of
      cardiorespiratory functions before and after feeding are related to birth weight
      and may provide markers that can help identify the most vulnerable of infants
      with small size at birth.

PMID- 19397553
TI  - The 1964 Nobel Prize for the discovery of the biosynthesis of cholesterol.

PMID- 19397554
TI  - Necrotizing enterocolitis following the use of intravenous immunoglobulin for
      haemolytic disease of the newborn.
AB  - AIM: To describe a series of patients who received intravenous immunoglobulin
      (IVIg) for the treatment of neonatal hyperbilirubinaemia and developed
      necrotizing enterocolitis (NEC) shortly thereafter. POPULATION AND RESULTS: We
      describe three healthy breastfed newly born infants with isoimmunization-derived
      hyperbilirubinaemia refractory to phototherapy who were treated with IVIg.
      Shortly after the perfusion finished they developed clinical and radiological
      signs compatible with NEC and needed antibiotic therapy, prolonged parenteral
      nutrition and even surgery in one case. Other conditions such as septicaemia or
      coagulopathy were ruled out. Microscopic examination of the resected intestine
      revealed the presence of disseminated thrombi obstructing multiple minor vessels
      of the mesenteric circulation. CONCLUSION: IVIg in the newborn period should be
      cautiously employed and always administered under strict medical control.

PMID- 19397555
TI  - Ultrasonography as predictor of permanent renal damage in infants with urinary
      tract infection.
AB  - AIM: To evaluate the ability of ultrasound (US) in infants (<1 year) with acute
      urinary tract infection (UTI), to identify those with permanent renal damage
      (PRD) at scintigraphy 1 year later. METHODS: US, dimercaptosuccinic acid
      scintigraphy and voiding cystourethrography were performed in 191 infants.
      RESULTS: US was abnormal in 46 infants (24%). PRD was found in 46 infants (24%);
      19 of these had abnormal US (sensitivity 41%). In 145 infants without PRD, 27 had
      abnormal US (specificity 81%). Dilating reflux or verified obstruction occurred
      in 21 (11%) infants, of whom 18 (86%) had PRD while 28 of 170 (16%) without such
      diagnoses had PRD. Of 16 infants with dilating reflux, 9 (sensitivity 56%) had
      abnormal US and 14 (88%) PRD. Dilatation at US was seen in 27 children; 7 of
      these had dilating reflux and 5 verified obstruction. CONCLUSION: US performed in
      association with acute UTI had limited ability to identify children with PRD at
      (99m)Tc-dimercaptosuccinic acid (DMSA) 1 year later, although abnormal renal size
      was a strong indicator of renal damage. The ability of US to identify children
      with dilating reflux was also limited. However, once detected at US, dilatation
      of the urinary tract was associated with dilating reflux or obstruction in half
      of the cases. Our study confirms that dilating reflux and obstruction are strong
      indicators of PRD but only half of those who developed PRD had such diagnoses.

PMID- 19397556
TI  - SNP discovery and haplotype analysis in the segmentally duplicated DRD5 coding
      region.
AB  - The dopamine receptor 5 gene (DRD5) holds much promise as a candidate locus for
      contributing to neuropsychiatric disorders and other diseases influenced by the
      dopaminergic system, as well as having potential to affect normal behavioral
      variation. However, detailed analyses of this gene have been complicated by its
      location within a segmentally duplicated chromosomal region. Microsatellites and
      SNPs upstream from the coding region have been used for association studies, but
      we find, using bioinformatics resources, that these markers all lie within a
      previously unrecognized second segmental duplication (SD). In order to accurately
      analyze the DRD5 locus for polymorphisms in the absence of contaminating
      pseudogene sequences, we developed a fast and reliable method for sequence
      analysis and genotyping within the DRD5 coding region. We employed restriction
      enzyme digestion of genomic DNA to eliminate the pseudogenes prior to PCR
      amplification of the functional gene. This approach allowed us to determine the
      DRD5 haplotype structure using 31 trios and to reveal additional rare variants in
      171 unrelated individuals. We clarify the inconsistencies and errors of the
      recorded SNPs in dbSNP and HapMap and illustrate the importance of using caution
      when choosing SNPs in regions of suspected duplications. The simple and
      relatively inexpensive method presented herein allows for convenient analysis of
      sequence variation in DRD5 and can be easily adapted to other duplicated genomic
      regions in order to obtain good quality sequence data.

PMID- 19397558
TI  - Inter- and extra-Indian admixture and genetic diversity in reunion island
      revealed by analysis of mitochondrial DNA.
AB  - Reunion Island is a French territory located in the western Indian Ocean. The
      genetic pattern of the Reunionese population has been shaped by contributions
      from highly contrasting regions of the world. Over the last 350 years, several
      migration waves and cultural and socio-economic factors have led to the emergence
      of six main ethnic groups in Reunion. India is one of the principal regions that
      contributed to the setting up of the Reunionese population. Diversity,
      demographic and admixture analyses were performed on mtDNA variation of the
      Reunionese of Indian ancestry, including the Malbar and Zarab ethnic groups, in
      order to question their history. Using a phylogeographical approach, we generated
      and analysed quantitative data on the contribution of the Indian parental
      populations. Furthermore, we showed that the settlement of Reunion Island by
      Indians did not involve a founder effect, except in the very beginning of the
      Reunionese settlement (at the end of the 17(th) century). The accuracy of our
      results was optimised by a re-evaluation of the classification of the Southern
      Asian mtDNA haplogroups. Finally, by comparing our results to a previous study
      dealing with the Reunionese population, we highlighted how ethno-historical data
      are critical for reconstructing the complex history of multiethnic populations.

PMID- 19397557
TI  - Genetic admixture in Brazilians exposed to infection with Leishmania chagasi.
AB  - Visceral leishmaniasis (VL) in northeast Brazil is a disease caused by infection
      with the protozoan Leishmania chagasi. Infection leads to variable clinical
      outcomes ranging from asymptomatic infection to potentially fatal disease. Prior
      studies suggest the genetic background of the host contributes to the development
      of different outcomes after infection, although it is not known if ancestral
      background itself influences outcomes. VL is endemic in peri-urban areas around
      the city of Natal in northeast Brazil. The population of northeast Brazil is a
      mixture of distinct racial and ethnic groups. We hypothesized that some sub
      populations may be more susceptible than others to develop different clinical
      outcomes after L. chagasi infection. Using microsatellite markers, we examined
      whether admixture of the population as a whole, or markers likely inherited from
      a distinct ethnic background, differed between individuals with VL, individuals
      with an asymptomatic infection, or individuals with no infection. There was no
      apparent significant difference in overall population admixture proportions among
      the three clinical phenotype groups. However, one marker on Chr. 22 displayed
      evidence of excess ancestry from putative ancestral populations among different
      clinical phenotypes, suggesting this region may contain genes determining the
      course of L. chagasi infection.

PMID- 19397559
TI  - Conditions masquerading as infantile haemangioma: Part 1.
AB  - Infantile haemangiomas are among the most common growths during infancy. Their
      rapid growth during infancy and vascularity can easily cause confusion with
      other, less common growths. This article focuses on the myriad of diagnostic
      mimics of haemangiomas, including other vascular anomalies, benign growths, and
      malignancies.

PMID- 19397561
TI  - Eczema workshops reduce severity of childhood atopic eczema.
AB  - An intervention study was conducted to assess the effectiveness of a nurse-led
      eczema workshop in reducing the severity of atopic eczema in infants, children
      and adolescents. Ninety-nine new patients referred to the Dermatology Department
      of The Royal Children's Hospital in Melbourne, Australia, for the management of
      atopic eczema were randomized to receive care from an eczema workshop or a
      dermatologist-led clinic. Patients were followed-up 4 weeks after the
      intervention. The primary outcome was the severity of eczema as determined by
      scores obtained using the Scoring of Atopic Dermatitis (SCORAD) index at a 4-week
      follow-up visit. The secondary outcome was a comparison of treatments used in
      both clinics. At the 4-week review the mean improvement in SCORAD was
      significantly greater in those patients attending the eczema workshop than those
      attending the dermatologist-led clinic (-9.93, 95% confidence interval -14.57 to 
      5.29, P < 0.001). Significantly more patients from the eczema workshop improved
      from moderate severity eczema at baseline to mild at review. There was greater
      adherence to eczema management in the eczema workshop compared with the
      dermatologist-led clinic. In this study, patients attending the eczema workshop
      had a greater improvement in eczema severity thanpatients attending a
      dermatologist-led clinic, supporting collaborative models of service provision.

PMID- 19397562
TI  - Electronic e-isotretinoin prescription chart: improving physicians' adherence to
      isotretinoin prescription guidelines.
AB  - Oral isotretinoin is a highly effective treatment for refractory nodulocystic
      acne. However, it can be associated with serious adverse effects such as
      teratogenicity and hepatitis. Inadequate cumulative dosing may also result in
      reduced therapeutic efficacy and higher disease relapse. A preliminary audit had
      previously revealed a poor and inconsistent adherence to local isotretinoin
      prescribing guidelines by physicians. To achieve greater than 90% adherence to
      isotretinoin guidelines for all acne patients prescribed systemic isotretinoin at
      the National Skin Centre, Singapore, key areas and the reasons for non-adherence
      were identified. A specifically designed 'one-stop' electronic isotretinoin chart
      was launched within the electronic medical records (EMR) system to address
      important safety areas; namely, informed patient consent, pregnancy testing,
      baseline laboratory tests, and automatic calculation of cumulative and target
      doses of isotretinoin. Physician adherence to prescribing guidelines improved
      from a baseline of 50-60% to greater than 90% (range 95-100%) for 30 consecutive
      months post intervention. The e-isotretinoin chart has resulted in significant
      improvement in physicians' adherence to isotretinoin prescription guidelines and
      highlights the utility of EMR technology in influencing safe prescribing
      behaviour among doctors.

PMID- 19397563
TI  - Successful treatment of female-pattern hair loss with spironolactone in a 9-year
      old girl.
AB  - A 9-year-old prepubertal girl with female pattern hair loss treated with
      spironolactone 100 mg orally per day had objective improvement demonstrated by
      regrowth observed clinically and on comparison of pre- and post-treatment
      stereotactic scalp photographs taken 6 months apart.

PMID- 19397564
TI  - Vulval and perianal inflammatory linear verrucous epidermal naevus.
AB  - Inflammatory linear verrucous epidermal naevus (ILVEN) is a rare form of
      epidermal naevus. It occurs as a linear dermatitic or psoriasiform plaque, with
      onset usually in the first 5 years of life. Lesions are characteristically
      intensely itchy. We present a case of ILVEN occurring on the vulva and perianal
      region of a 6-year-old girl. The lesion was initially thought to be an area of
      lichenified dermatitis; however, treatment with even super-potent topical
      corticosteroids did not significantly improve the inflammation. A biopsy was
      performed and histopathological examination showed characteristic features. ILVEN
      is frequently refractory to topical treatment and surgical excision of lesions
      may be an option for relief of symptoms. ILVEN occasionally presents in the
      inguinogenital region and in this area may, like many vulval naevi, be
      misdiagnosed as vulvitis, psoriasis, genital warts or sexual abuse.

PMID- 19397565
TI  - Vulval fixed drug eruption due to paracetamol.
AB  - Paracetamol is a readily available non-prescription analgesic. Fixed drug
      eruption (FDE) is a well-reported side effect of paracetamol, usually the
      classic, pigmenting type. In women, it may present as a chronic, erosive
      vulvitis. We describe a case of FDE due to paracetamol presenting as a chronic
      erosive vulvitis in an older woman taking multiple medications. Diagnosis was
      delayed because paracetamol is available without prescription, taken
      intermittently and may be omitted from the clinical history. Cessation of
      paracetamol led to prompt resolution of symptoms. Consideration should be given
      to paracetamol as a cause of FDE presenting as a chronic erosive vulvitis.

PMID- 19397566
TI  - Delayed diagnosis of Gorlin's syndrome in a renal transplant recipient.
AB  - A 35-year-old woman was referred to the dedicated dermatology clinic for RTR. She
      underwent her first renal transplant at 18 years of age due to chronic renal
      failure following reflux nephropathy of the single right kidney (left kidney
      agenesis). She has since then had two further transplants. During clinical
      examination she was noted to have at least 16 basal cell carcinomas (BCC) and
      there are records in the case notes of 10 BCC having being excised and confirmed
      histologically in the past. By contrast, she had only had two squamous cell
      carcinomas (SCC) excised. She was also noted to have distinctive facial features,
      a kyphoscoliosis and palmar pits, and a diagnosis of Gorlin's (naevoid BCC)
      syndrome (GS) was made. Although immunosuppression may have contributed to the
      multiplicity of her BCC, the contrasting very small number of SCC is unusual in
      an organ transplant recipient and this alerted the authors to the diagnosis of
      GS.

PMID- 19397567
TI  - Allergic contact dermatitis from exposure to Grevillea robusta in New Zealand.
AB  - There are a number of reports in the literature of allergic contact dermatitis as
      a result of exposure to the sawdust and plant parts of Grevillea robusta. While
      this tree is prevalent in New Zealand, there seems to have been no previous
      published accounts of contact dermatitis, although anecdotal evidence indicates
      that such cases may be common. Two brief case reports are provided regarding
      severe phytodermatitis to G. robusta among professional arborists in New Zealand.
      As with other common plants capable of inducing allergic contact dermatitis,
      greater awareness among arborists, orchardists, forestry workers, gardeners, and
      health professionals will likely result in a reduction of cases.

PMID- 19397568
TI  - Successful treatment of lymphomatoid papulosis with photodynamic therapy.
AB  - A 40-year-old woman presented with a prolonged history of recurrent crops of
      erythematous papules and nodules on her abdomen, arms and legs. Histological
      examination of a cutaneous biopsy revealed Type A lymphomatoid papulosis. Over a
      3-year period, some of the patient's lesions had proven to be resistant to
      treatment with topical and intralesional corticosteroids and systemic agents
      including methotrexate, tetracycline and nicotinamide. These resistant lesions
      were treated with two sessions of methyl aminolevulinate photodynamic therapy
      given 1 week apart. Review 11 months post-photodynamic therapy demonstrated
      complete clinical clearance at the treatment site. While photodynamic therapy is
      considered a standard non-surgical treatment option for non-melanoma skin cancers
      and has been described in a number of non-oncological indications, this is the
      first report of its use in lymphomatoid papulosis.

PMID- 19397569
TI  - Solitary mastocytoma occurring at a site of trauma.
AB  - We describe a patient with a solitary mastocytoma arising at a site of trauma.
      The patient was born with the umbilical cord wrapped around her right thigh and
      subsequently developed a solitary mastocytoma in the exact site and distribution
      of this injury. The pathogenesis of mast cell proliferation in solitary
      mastocytoma is not completely understood. Cytokines released after injury, such
      as stem cell factor, may stimulate the proliferation of mast cells, as well as
      fibroblasts and melanocytes to form a mastocytoma. Mast cells in a newborn may be
      more sensitive to stem cell factor in the presence of cytokines released after
      injury due to an increased density of c-kit receptors. We present our patient and
      review the literature to support a hypothesis that this condition represents a
      reactive, and not neoplastic, process.

PMID- 19397570
TI  - Unusual presentation of GLUT-1 positive infantile haemangioma.
AB  - Infantile haemangiomas are usually not present at birth. This is a case of a
      female infant with an atypical congenital vascular tumour present at birth which
      ulcerated in the first few days of life, involuted over several months and showed
      histopathological features in keeping with either an involuting GLUT-1 positive
      infantile haemangioma or a reticular haemangioma of infancy. The initial clinical
      presentation was atypical for an infantile haemangiomas and for a congenital
      haemangioma, however the histopathology and immunohistochemistry assisted with
      confirmation of the diagnosis. Vacuum-assisted closure (VAC) therapy aided in the
      complete healing of the ulcerated infantile haemangioma which was not achievable
      with conventional dressings.

PMID- 19397571
TI  - Pyogenic granuloma complicating pulsed-dye laser therapy for cherry angioma.
AB  - A 37 year-old-woman presented for cosmetic removal of a 7-mm (diameter) cherry
      angioma on her right anterior thigh. Various treatment options were discussed and
      removal of the lesion using pulsed-dye laser was carried out. The patient
      returned 5 weeks later complaining of bleeding from the treatment site, which on
      examination showed a 23 x 23-mm friable nodular lesion with the typical
      appearance of a pyogenic granuloma. This lesion was removed by shave excision,
      curettage and electrodessication. Histopathological examination confirmed the
      diagnosis of pyogenic granuloma. This is a rare occurrence post pulsed-dye laser
      therapy that physicians may choose to discuss with patients prior to performing
      this procedure.

PMID- 19397572
TI  - Subungual and periungual congenital blue naevus.
AB  - Subungual pigmented lesions should raise concern about malignant melanoma. Blue
      naevus of the nail apparatus is a rare entity, with only ten cases described in
      the literature. We report a 21-year-old Hispanic woman with a slowly enlarging
      1.7 x 2.3-cm subungual and periungual pigmented plaque present since birth on her
      right second toe. Initial biopsy was consistent with a blue naevus of the
      cellular type and, given the recent clinical change and periungual extension,
      complete excision was recommended. The entire nail unit was resected down to
      periosteum with prior avulsion of the nail plate. Reconstruction was performed
      with a full-thickness skin graft. Follow up at 1 year revealed well-healed graft
      and donor sites with complete return of function. We present a case of a
      congenital subungual and periungual blue naevus of the cellular type and review
      the literature on this rare presentation of a congenital blue naevus.

PMID- 19397578
TI  - A latent class model with hidden Markov dependence for array CGH data.
AB  - Array CGH is a high-throughput technique designed to detect genomic alterations
      linked to the development and progression of cancer. The technique yields
      fluorescence ratios that characterize DNA copy number change in tumor versus
      healthy cells. Classification of tumors based on aCGH profiles is of scientific
      interest but the analysis of these data is complicated by the large number of
      highly correlated measures. In this article, we develop a supervised Bayesian
      latent class approach for classification that relies on a hidden Markov model to
      account for the dependence in the intensity ratios. Supervision means that
      classification is guided by a clinical endpoint. Posterior inferences are made
      about class-specific copy number gains and losses. We demonstrate our technique
      on a study of brain tumors, for which our approach is capable of identifying
      subsets of tumors with different genomic profiles, and differentiates classes by
      survival much better than unsupervised methods.

PMID- 19397579
TI  - Semiparametric models of time-dependent predictive values of prognostic
      biomarkers.
AB  - Rigorous statistical evaluation of the predictive values of novel biomarkers is
      critical prior to applying novel biomarkers into routine standard care. It is
      important to identify factors that influence the performance of a biomarker in
      order to determine the optimal conditions for test performance. We propose a
      covariate-specific time-dependent positive predictive values curve to quantify
      the predictive accuracy of a prognostic marker measured on a continuous scale and
      with censored failure time outcome. The covariate effect is accommodated with a
      semiparametric regression model framework. In particular, we adopt a smoothed
      survival time regression technique (Dabrowska, 1997, The Annals of Statistics 25,
      1510-1540) to account for the situation where risk for the disease occurrence and
      progression is likely to change over time. In addition, we provide asymptotic
      distribution theory and resampling-based procedures for making statistical
      inference on the covariate-specific positive predictive values. We illustrate our
      approach with numerical studies and a dataset from a prostate cancer study.

PMID- 19397580
TI  - Bayesian calibration of a stochastic kinetic computer model using multiple data
      sources.
AB  - In this article, we describe a Bayesian approach to the calibration of a
      stochastic computer model of chemical kinetics. As with many applications in the
      biological sciences, the data available to calibrate the model come from
      different sources. Furthermore, these data appear to provide somewhat conflicting
      information about the model parameters. We describe a modeling framework that
      allows us to synthesize this conflicting information and arrive at a consensus
      inference. In particular, we show how random effects can be incorporated into the
      model to account for between-individual heterogeneity that may be the source of
      the apparent conflict.

PMID- 19397581
TI  - Uncovering a latent multinomial: analysis of mark-recapture data with
      misidentification.
AB  - Natural tags based on DNA fingerprints or natural features of animals are now
      becoming very widely used in wildlife population biology. However, classic
      capture-recapture models do not allow for misidentification of animals which is a
      potentially very serious problem with natural tags. Statistical analysis of
      misidentification processes is extremely difficult using traditional likelihood
      methods but is easily handled using Bayesian methods. We present a general
      framework for Bayesian analysis of categorical data arising from a latent
      multinomial distribution. Although our work is motivated by a specific model for
      misidentification in closed population capture-recapture analyses, with crucial
      assumptions which may not always be appropriate, the methods we develop extend
      naturally to a variety of other models with similar structure. Suppose that
      observed frequencies f are a known linear transformation f=A'x of a latent
      multinomial variable x with cell probability vector pi=pi(theta). Given that full
      conditional distributions [theta | x] can be sampled, implementation of Gibbs
      sampling requires only that we can sample from the full conditional distribution
      [x | f, theta], which is made possible by knowledge of the null space of A'. We
      illustrate the approach using two data sets with individual misidentification,
      one simulated, the other summarizing recapture data for salamanders based on
      natural marks.

PMID- 19397582
TI  - Improved logrank-type tests for survival data using adaptive weights.
AB  - For testing for treatment effects with time-to-event data, the logrank test is
      the most popular choice and has some optimality properties under proportional
      hazards alternatives. It may also be combined with other tests when a range of
      nonproportional alternatives are entertained. We introduce some versatile tests
      that use adaptively weighted logrank statistics. The adaptive weights utilize the
      hazard ratio obtained by fitting the model of Yang and Prentice (2005, Biometrika
      92, 1-17). Extensive numerical studies have been performed under proportional and
      nonproportional alternatives, with a wide range of hazard ratios patterns. These
      studies show that these new tests typically improve the tests they are designed
      to modify. In particular, the adaptively weighted logrank test maintains
      optimality at the proportional alternatives, while improving the power over a
      wide range of nonproportional alternatives. The new tests are illustrated in
      several real data examples.

PMID- 19397583
TI  - Estimating HIV incidence based on combined prevalence testing.
AB  - Knowledge of incidence rates of HIV and other infectious diseases is important in
      evaluating the state of an epidemic as well as for designing interventional
      studies. Estimation of disease incidence from longitudinal studies can be
      expensive and time consuming. Alternatively, Janssen et al. (1998, Journal of the
      American Medical Association 280, 42-48) proposed the estimation of HIV incidence
      at a single point in time based on the combined use of a standard and "detuned"
      antibody assay. This article frames the problem from a longitudinal perspective,
      from which the maximum likelihood estimator of incidence is determined and
      compared with the Janssen estimator. The formulation also allows estimation for
      general situations, including different batteries of tests among subjects,
      inclusion of covariates, and a comparative evaluation of different test batteries
      to help guide study design. The methods are illustrated with data from an HIV
      interventional trial and a seroprevalence survey recently conducted in Botswana.

PMID- 19397584
TI  - Improving power for testing genetic association in case-control studies by
      reducing the alternative space.
AB  - To detect association between a genetic marker and a disease in case-control
      studies, the Cochran-Armitage trend test is typically used. The trend test is
      locally optimal when the genetic model is correctly specified. However, in
      practice, the underlying genetic model, and hence the optimal trend test, are
      usually unknown. In this case, Pearson's chi-squared test, the maximum of three
      trend test statistics (optimal for the recessive, additive, and dominant models),
      and the test based on genetic model selection (GMS) are useful. In this article,
      we first modify the existing GMS method so that it can be used when the risk
      allele is unknown. Then we propose a new approach by excluding a genetic model
      that is not supported by the data. Using either the model selection or exclusion,
      the alternative space is reduced conditional on the observed data, and hence the
      power to detect a true association can be increased. Simulation results are
      reported and the proposed methods are applied to the genetic markers identified
      from the genome-wide association studies conducted by the Wellcome Trust Case
      Control Consortium. The results demonstrate that the genetic model exclusion
      approach usually performs better than existing methods under its worst situation
      across scientifically plausible genetic models we considered.

PMID- 19397585
TI  - Variable selection for semiparametric mixed models in longitudinal studies.
AB  - We propose a double-penalized likelihood approach for simultaneous model
      selection and estimation in semiparametric mixed models for longitudinal data.
      Two types of penalties are jointly imposed on the ordinary log-likelihood: the
      roughness penalty on the nonparametric baseline function and a nonconcave
      shrinkage penalty on linear coefficients to achieve model sparsity. Compared to
      existing estimation equation based approaches, our procedure provides valid
      inference for data with missing at random, and will be more efficient if the
      specified model is correct. Another advantage of the new procedure is its easy
      computation for both regression components and variance parameters. We show that
      the double-penalized problem can be conveniently reformulated into a linear mixed
      model framework, so that existing software can be directly used to implement our
      method. For the purpose of model inference, we derive both frequentist and
      Bayesian variance estimation for estimated parametric and nonparametric
      components. Simulation is used to evaluate and compare the performance of our
      method to the existing ones. We then apply the new method to a real data set from
      a lactation study.

PMID- 19397586
TI  - Structural nested mean models for assessing time-varying effect moderation.
AB  - This article considers the problem of assessing causal effect moderation in
      longitudinal settings in which treatment (or exposure) is time varying and so are
      the covariates said to moderate its effect. Intermediate causal effects that
      describe time-varying causal effects of treatment conditional on past covariate
      history are introduced and considered as part of Robins' structural nested mean
      model. Two estimators of the intermediate causal effects, and their standard
      errors, are presented and discussed: The first is a proposed two-stage regression
      estimator. The second is Robins' G-estimator. The results of a small simulation
      study that begins to shed light on the small versus large sample performance of
      the estimators, and on the bias-variance trade-off between the two estimators are
      presented. The methodology is illustrated using longitudinal data from a
      depression study.

PMID- 19397587
TI  - Nondestructive, stereological estimation of canopy surface area.
AB  - We describe a stereological procedure to estimate the total leaf surface area of
      a plant canopy in vivo, and address the problem of how to predict the variance of
      the corresponding estimator. The procedure involves three nested systematic
      uniform random sampling stages: (i) selection of plants from a canopy using the
      smooth fractionator, (ii) sampling of leaves from the selected plants using the
      fractionator, and (iii) area estimation of the sampled leaves using point
      counting. We apply this procedure to estimate the total area of a chrysanthemum
      (Chrysanthemum morifolium L.) canopy and evaluate both the time required and the
      precision of the estimator. Furthermore, we compare the precision of point
      counting for three different grid intensities with that of several standard leaf
      area measurement techniques. Results showed that the precision of the plant leaf
      area estimator based on point counting is high. Using a grid intensity of 1.76
      cm(2)/point we estimated plant and canopy surface areas with accuracies similar
      to or better than those obtained using image analysis and a commercial leaf area
      meter. For canopy surface areas of approximately 1 m(2) (10 plants), the
      fractionator leaf approach with sampling fraction equal to 1/9 followed by point
      counting using a 4.3 cm(2)/point grid produced a coefficient of error of less
      than 7%. The smooth fractionator can be used to ensure that the additional
      contribution to the estimator variance due to between-plant variability is small.

PMID- 19397588
TI  - Bayesian models for multiple outcomes nested in domains.
AB  - We consider the problem of estimating the effect of exposure on multiple
      continuous outcomes, when the outcomes are measured on different scales and are
      nested within multiple outcome classes, or "domains." Our Bayesian model extends
      the linear mixed models approach to allow the exposure effect to differ across
      domains and across outcomes within domains. Our model can be parameterized to
      allow shrinkage of the effects within the different levels of nesting, or to
      allow fixed domain-specific effects with no shrinkage. Our model also allows
      covariate effects to differ across outcomes and domains. Our methodology is
      applied to data on prenatal methylmercury exposure and multiple outcomes in four
      domains measured at 9 years of age on children enrolled in the Seychelles Child
      Development Study. We use three different priors and found that our main
      conclusions were not sensitive to the choice of prior. Simulation studies examine
      the model performance under alternative scenarios. Our results demonstrate that a
      sizeable increase in power is possible.

PMID- 19397589
TI  - Assessing vaccine effects in repeated low-dose challenge experiments.
AB  - Evaluation of HIV vaccine candidates in nonhuman primates (NHPs) is a critical
      step toward developing a successful vaccine to control the HIV pandemic.
      Historically, HIV vaccine regimens have been tested in NHPs by administering a
      single high dose of the challenge virus. More recently, evaluation of candidate
      HIV vaccines has entailed repeated low-dose challenges, which more closely mimic
      typical exposure in natural transmission settings. In this article, we consider
      evaluation of the type and magnitude of vaccine efficacy from such experiments.
      Based on the principal stratification framework, we also address evaluation of
      potential immunological surrogate endpoints for infection.

PMID- 19397590
TI  - Arsenic trioxide suppresses paclitaxel-induced mitotic arrest.
AB  - OBJECTIVES: To understand if there exists a functional interaction between
      arsenic trioxide and paclitaxel in vitro. MATERIALS AND METHODS: HeLa and HCT116
      (rho53(+/+) and rho53(-/-)) cells were treated with As2O3 and/or paclitaxel for
      various times. Treated cells were collected for analyses using a combination of
      flow cytometry, fluorescence microscopy and Western blotting. RESULTS: Because
      As(2)O(3) is capable of inhibiting tubulin polymerization and inducing mitotic
      arrest, we examined whether there existed any functional interaction between
      As(2)O(3) and paclitaxel, a well-known microtubule poison. Flow cytometry and
      fluorescence microscopy revealed that although As(2)O(3) alone caused a moderate
      level of mitotic arrest, it greatly attenuated paclitaxel-induced mitotic arrest
      in cells with p53 deficiency. Western blot analysis showed that As(2)O(3)
      significantly blocked phosphorylation of BubR1, Cdc20, and Cdc27 in cells treated
      with paclitaxel, suggesting that arsenic compromised the activation of the
      spindle checkpoint. Our further studies revealed that the attenuation of
      paclitaxel-induced mitotic arrest by As(2)O(3) resulted primarily from sluggish
      cell cycle progression at S phase but not enhanced mitotic exit. CONCLUSION: The
      observations that As(2)O(3) has a negative impact on the cell cycle checkpoint
      activation by taxol should have significant clinical implications because the
      efficacy of taxol in the clinics is associated with its ability to induce mitotic
      arrest and subsequent mitotic catastrophe.

PMID- 19397591
TI  - In vitro three-dimensional modelling of human ovarian surface epithelial cells.
AB  - OBJECTIVES: Ninety percent of malignant ovarian cancers are epithelial and
      thought to arise from the ovarian surface epithelium (OSE). We hypothesized that
      biological characteristics of primary OSE cells would more closely resemble OSE
      in vivo if established as three-dimensional (3D) cultures. MATERIALS AND METHODS:
      OSE cells were cultured as multicellular spheroids (MCS) (i) in a rotary cell
      culture system (RCCS) and (ii) on polyHEMA-coated plastics. The MCSs were
      examined by electron microscopy and compared to OSE from primary tissues and
      cells grown in 2D. Annexin V FACS analysis was used to evaluate apoptosis and
      expression of extracellular matrix (ECM) proteins was analysed by
      immunohistochemical staining. RESULTS: On polyHEMA-coated plates, OSE spheroids
      had defined internal architecture. RCCS MCSs had disorganized structure and
      higher proportion of apoptotic cells than polyHEMA MCSs and the same cells grown
      in 2D culture. In 2D, widespread expression of AE1/AE3, laminin and vimentin were
      undetectable by immunohistochemistry, whereas strong expression of these proteins
      was observed in the same cells grown in 3D culture and in OSE on primary tissues.
      CONCLUSIONS: Physiological and biological features of OSE cells grown in 3D
      culture more closely resemble characteristics of OSE cells in vivo than when
      grown by classical 2D approaches. It is likely that establishing in vitro 3D OSE
      models will lead to greater understanding of the mechanisms of neoplastic
      transformation in epithelial ovarian cancers.

PMID- 19397592
TI  - Effects of core binding factor alpha1 or bone morphogenic protein-2
      overexpression on osteoblast/cementoblast-related gene expressions in NIH3T3
      mouse cells and dental follicle cells.
AB  - OBJECTIVES: Bone morphogenic protein-2 (BMP-2) has long been used to promote bone
      and periodontal regeneration, while core binding factor alpha1 (CBFA1) plays
      important roles in both osteogenic differentiation and tooth morphogenesis. The
      aim of this study was to evaluate the effects of CBFA1 or BMP-2 overexpression on
      osteoblast/cementoblast-related gene expressions in NIH3T3 cells and dental
      follicle cells (DFCs). MATERIALS AND METHODS: CBFA1 or BMP-2 overexpression in
      NIH3T3 and DFCs was achieved by infection with retroviral vectors containing
      CBFA1 or BMP-2 cDNA. Cells stably integrated with CBFA1 or BMP-2 cDNA were
      selected with G418 for 14 days. Western blotting, real-time reverse transcriptase
      polymerase chain reaction, and in vitro mineralization assay were performed to
      evaluate effects of CBFA1 or BMP-2 overexpression in cells undergoing
      osteoblast/cementoblast differentiation. RESULTS: Our results demonstrated that
      osteoblast/cementoblast-related gene expression levels in CBFA1-overexpressing
      NIH3T3 cells were higher than those in BMP-2-overexpressing cells. More mineral
      nodules were observed in CBFA1-overexpressing NIH3T3 cells than in BMP-2
      overexpressing cells. CBFA1 overexpression in DFCs also increased
      osteoblast/cementoblast-related gene expression and promoted mineral nodule
      formation. However, no significant changes in gene expression levels nor mineral
      nodule formation were found in BMP-2-overexpressing DFCs when compared with empty
      vector transduced DFCs. CONCLUSIONS: CBFA1 overexpression up-regulated expression
      levels of osteoblast/cementoblast-related genes and enhanced in vitro osteogenic
      differentiation more efficiently than BMP-2 in both NIH3T3 cells and DFCs.

PMID- 19397593
TI  - Epithelial stem cell-related alterations in Trichinella spiralis-infected small
      intestine.
AB  - OBJECTIVES: Infection of mice with the parasite Trichinella spiralis leads to
      small intestinal inflammation, characterized by changes in mucosal architecture
      and subpopulations of epithelial cells. This model has been used to explore
      changes in the epithelial proliferative cell population and expression of
      transforming growth factor-beta (TGF-beta). MATERIALS AND METHODS: Histochemical
      and immunohistochemical studies were undertaken in duodenal samples. Location and
      number of Ki-67-positive cells were assessed using Score and Wincrypts program.
      Changes in mRNA transcripts were studied by real-time RT-PCR. RESULTS: T.
      spiralis infection induced an increase in total number of proliferative (Ki-67
      positive) cells per half crypt on day 2 post-infection. Transcription of Math1, a
      transcription factor required for secretory cell differentiation in the
      intestine, was up-regulated on days 6-18 post-infection. At these time points,
      numbers of Paneth cells at the crypt base were also increased and the epithelial
      proliferative zone was shifted up the crypt-villus axis. Transcription of TGF
      beta isoforms within the small intestine was up-regulated on days 6 and 12 post
      infection, but anti-TGF-beta antibody treatment had no effect on T. spiralis
      induced changes in mucosal architecture or increase in Paneth/intermediate cells.
      CONCLUSIONS: T. spiralis infection promotes an initial increase in small
      intestinal epithelial proliferation and subsequent cell differentiation along the
      secretory cell lineage. The resulting increase in numbers of Paneth cells at the
      crypt base causes the proliferative zone to move up the crypt-villus axis.
      Further studies are required to determine the significance of an increase in the
      expression of TGF-beta transcripts.

PMID- 19397595
TI  - Services for children: emerging as a genuine priority within health policy at
      last?

PMID- 19397594
TI  - Progenitor cell self-renewal and cyclic neutropenia.
AB  - OBJECTIVES: Cyclic neutropenia (CN) is a rare genetic disorder where patients
      experience regular cycling of numbers of neutrophils and various other
      haematopoietic lineages. The nadir in neutrophil count is the main source of
      problems due to risk of life-threatening infections. Patients with CN benefit
      from granulocyte colony stimulating factor therapy, although cycling persists.
      Mutations in neutrophil elastase gene (ELA2) have been found in more than half of
      patients with CN. However, neither connection between phenotypic expression of
      ELA2 and CN nor the mechanism of cycling is known. MATERIALS AND METHODS:
      Recently, a multicompartment model of haematopoiesis that couples stem cell
      replication with marrow output has been proposed. In the following, we couple
      this model of haematopoiesis with a linear feedback mechanism via G-CSF. RESULTS:
      We propose that the phenotypic effect of ELA2 mutations leads to reduction in
      self-renewal of granulocytic progenitors. The body responds by overall relative
      increase of G-CSF and increasing progenitor cell self-renewal, leading to cell
      count cycling. CONCLUSION: The model is compatible with available experimental
      data and makes testable predictions.

PMID- 19397596
TI  - The therapeutic alliance.

PMID- 19397597
TI  - Protective factors relating to decreased risks of adolescent suicidal behaviour.
AB  - BACKGROUND: Suicide has been identified as one of the three leading causes of
      death in adolescents and young adults. No previous study in China has tested the
      association between protective factors and urban adolescents' suicidal
      behaviours. In this study we tested the hypothesis that suicidal behaviours would
      be associated with multiple protective factors. METHODS: A stratified random of
      9015 students from 100 junior middle schools in Beijing, Hangzhou, Wuhan and
      Urumqi completed the Chinese version of Global School-Based Student Health
      Survey. RESULTS: Overall, 17.4% of students had seriously considered attempting
      suicide, and 8.1% had made a specific plan to attempt suicide during the 12
      months preceding the survey. The students in Wuhan (18.7%) and Urumqi (20.8%)
      cities were significantly more likely than students in Beijing (14.4%) and
      Hangzhou (14.4%) to have suicidal ideation (chi2 = 45.9, P < 0.001). Female
      students were significantly more likely than male students to have suicidal
      ideation and have made suicide attempts [odds ratio (OR) = 1.4, P < 0.001].
      Results indicated that the rates of suicidal ideation and suicide attempts
      increased with age (OR = 1.44, P < 0.001). Multivariate logistic regression
      models showed that suicide risk tended to decrease significantly when 'days of
      missed classes or school without permission were less than one', and when
      students thought students in their school were kind and helpful most of the time
      or always', 'parents or guardians checked to see if homework was done most of the
      time or always', 'parents or guardians understood their problems and worries most
      of the time or always' and 'parents or guardians really know what they are doing
      with their free time most of the time or always'. CONCLUSIONS: Adolescent suicide
      behaviour should be a serious problem. Measures can be taken to prevent suicide
      by observing the factors significantly linked to suicidal behaviour. Steps can
      then be taken to identify adolescents who have serious suicidal ideation so that
      intervention can be taken to reduce the suicidal rate.

PMID- 19397598
TI  - Health risks for older US adolescents in foster care: the significance of
      important others' health behaviours on youths' health and health behaviours.
AB  - BACKGROUND: Little research to date has examined older foster care youths'
      physical health and the associated health behaviours of the youth and important
      people in their lives (parents, peers and important non-parental adults).
      METHODS: Older US foster care youth (n= 188) completed surveys on multiple
      indicators of self-report physical health, including number of chronic health
      problems, overall health and sick symptoms, as well as their own health
      compromising behaviours and the health-compromising behaviours of important
      others. RESULTS: The findings suggested that boys, particularly those placed in
      non-kin foster homes and group homes, appeared to have poorer health than did
      boys in these placement settings. Girls, however, engaged in similar levels of
      health-compromising behaviours as boys. Furthermore, the health-compromising
      behaviours of peers and important non-parental adults (VIPs), but not parents,
      were associated with youths' health behaviours, which, in turn, were associated
      with the physical health status of the foster care youth. CONCLUSION: Youth
      report high levels of health-related problems and involvement in health
      compromising behaviours. Healthcare practitioners can help to improve the health
      and well-being of children in foster care by becoming informed about adolescent
      health behaviours, as well as the health behaviours of their peers and other
      important non-parental adults.

PMID- 19397599
TI  - Objectively measured habitual physical activity in a highly obesogenic
      environment.
AB  - BACKGROUND: While the prevalence of overweight and obesity among children
      continues to grow nationally, prevalence in the North-East of England is among
      the highest in the UK. The objective of this study was to investigate the
      habitual physical activity levels in a particularly obesogenic environment in the
      North-East of England. METHODS: Eight primary schools were selected using a
      stratified random sampling frame ranking average deprivation levels.
      Participating children (n = 246, mean age 10 years) wore an accelerometer
      (Actigraph, GT-256) over five consecutive days (weekend plus three weekdays).
      Total daily moderate-to-vigorous intensity physical activity was calculated using
      thresholds by Puyau and colleagues. RESULTS: Only 7% (17/246) of children were
      sufficiently active. Boys were more physically active than girls (766 +/- 268 vs.
      641 +/- 202 counts/min, 95% CI for the difference 63-186 cpm.). Total physical
      activity was not influenced significantly by deprivation levels or weight status,
      and there were no significant differences in physical activity between school or
      weekend days. CONCLUSIONS: The North-East of England is a recognized 'hot spot'
      for paediatric obesity and the present study shows that low levels of habitual
      physical activity are typical. Choice of accelerometry threshold affects both the
      apparent amount of physical activity and the ability to detect groups with
      particularly low levels of physical activity.

PMID- 19397600
TI  - Changes in physical activity in pre-schoolers and first-grade children:
      longitudinal study in the Czech Republic.
AB  - BACKGROUND: The transition from kindergarten to first year at school is
      associated with a variety of psychosocial changes in children. The aim of this
      longitudinal study was to identify the changes in children's physical activity
      (PA) upon entry to first year at school; and to identify the days of the school
      week that exhibit low PA. METHODS: We monitored the PA levels of 176 children
      twice: initially in kindergarten and again in first-year classes at school. The
      age (mean +/- standard deviation) of children at kindergarten was 5.7 +/- 0.5
      years and 6.7 +/- 0.5 years at the first year of elementary school. We evaluated
      PA employing the activity energy expenditure (AEE - kcal/kg/day) from Caltrac
      accelerometer and daily amount of steps (STEPS) from Yamax pedometer.
      Participants were monitored over 7 days to include a weekend. RESULTS: The mean
      AEE was 11.5 in pre-school girls and 12.9 kcal/kg/day in boys; and STEPS were
      9923 steps/day in girls and 11 864 in boys on weekdays. At weekends, it was 11.5
      kcal/kg/day in girls and 12.7 kcal/kg/day in boys and 10 606 steps/day in girls
      and 11 182 steps/day in boys. The mean AEE and STEPS in first-grade girls and
      boys was 9.9 and 9.8 kcal/kg/day respectively, and 7911 and 8252 steps/day
      respectively on weekdays, and 8.8 and 9.0 kcal/kg/day and 6872 and 7194 steps/day
      respectively at weekends. First-grade school children had significantly lower PA
      than pre-school children on weekdays (P < 0.0001) and at weekends (P < 0.0001).
      Decline in PA on weekdays was during time spent at school (P < 0.0001) and not
      during after-school children's leisure time. CONCLUSION: The parts of the week
      when first-grade school children show low PA are the times spent in lessons and
      in after-school nursery and at weekends. PA needs to be promoted using
      intervention programmes mainly during the after-school nursery programmes and at
      weekends.

PMID- 19397601
TI  - Understanding the medically unexplained: emotional and familial influences on
      children's somatic functioning.
AB  - BACKGROUND: Many youth experience impairing, unexplained somatic complaints.
      Psychosocial models of child somatization have primarily focused on parent
      somatic functioning. Although helpful in understanding child somatization, this
      narrow focus on parental factors leaves a large proportion of the variance
      unaccounted for when explaining children's general somatic functioning. The goal
      of this investigation is to extend current models of child somatization by
      collectively examining the influence of parent somatization and child emotional
      functioning. METHODS: Forty-two children (50% male; M age = 9.11) reported on
      their somatic symptoms, emotion awareness skills, and negative affect. Parents
      reported on their own somatic symptoms and their child's somatic symptoms and
      emotion regulation skills. RESULTS: Regression analyses indicated that poor
      awareness of emotional experiences and frequency of negative effect predicted
      child-reported somatic symptoms. Parental somatic symptoms and parent reports of
      children's emotion regulation difficulties predicted mother-reported child
      somatic symptoms. Only parental somatic symptoms significantly predicted father
      reported child somatic symptoms. CONCLUSIONS: These results suggest that models
      of child somatization should consider both family - (e.g. parent somatization)
      and child-level (e.g. emotional functioning) variables. The discrepancies between
      parent and child report of youth somatic symptoms underscore the importance of
      including multiple reporters on symptomatology in research and clinical settings.
      Suggestions for future research are provided.

PMID- 19397602
TI  - Chronic illnesses in Canadian children: what is the effect of illness on academic
      achievement, and anxiety and emotional disorders?
AB  - BACKGROUND: Survival rates of children with a chronic illness is at an all-time
      high. Up to 98% of children suffering from a chronic illness, which may have been
      considered fatal in the past, now reach early adulthood. It is estimated that as
      many as 30% of school-aged children are affected by a chronic illness. For this
      population of children, the prevalence of educational and psychological problems
      is nearly double in comparison with the general population. METHODS: This study
      investigated the educational and psychological effects of childhood chronic
      illness among 1512 Canadian children (ages 10-15 years). This was a retrospective
      analysis using data from the National Longitudinal Survey of Children and Youth,
      taking a cross-sectional look at the relationships between childhood chronic
      illnesses, performance on a Mathematics Computation Exercise (MCE) and ratings on
      an Anxiety and Emotional Disorder (AED) scale. RESULTS: When AED ratings and
      educational handicaps were controlled for, children identified with chronic
      illnesses still had weaker performance on the MCE. Chronic illness did not appear
      to have a relationship with children's AED ratings. The regression analysis
      indicated that community type and illness were the strongest predictors of MCE
      scores. CONCLUSIONS: The core research implications of this study concern
      measurement issues that need to be addressed in future large-scale studies.
      Clinical implications of this research concern the need for co-ordinated services
      between the home, hospital and school settings so that services and programmes
      focus on the ecology of the child who is ill.

PMID- 19397603
TI  - Comparing probable case identification of developmental coordination disorder
      using the short form of the Bruininks-Oseretsky Test of Motor Proficiency and the
      Movement ABC.
AB  - Aim Despite its widespread current use in research and its potential for future
      application, the validity of the short form of the Bruininks-Oseretsky Test of
      Motor Proficiency (BOTMP-SF) when administered by trained lay assessors is not
      known. This paper reports the results of case identification using the Movement
      Assessment Battery for Children (M-ABC) in a group of children scoring below the
      sixth percentile on the BOTMP-SF. Methods The BOTMP-SF was administered by
      trained research assistants to 2058 children. In total, 24 of 128 children aged
      10 (n = 10), 11 (n = 10) or 12 (n = 4) scoring below the sixth percentile were
      randomly selected for further assessment by a paediatric occupational therapist
      using the M-ABC and the Kaufman Brief Intelligence Test. Results Twenty-one of 24
      children positive for motor co-ordination problems on the BOTMP-SF scored below
      the 15th percentile of the M-ABC, a positive predictive value (PPV) of 0.88 [95%
      confidence interval (CI) = 0.69 to 0.96]. Fifteen of these children were below
      the fifth percentile (PPV = 0.63; 95% CI = 0.43 to 0.79). Conclusions The BOTMP
      SF seems to be a reasonable alternative to case identification when clinical
      assessment with the M-ABC is not feasible. Further research is needed to examine
      the sensitivity and specificity of the short form when used for this purpose.

PMID- 19397604
TI  - Twin-singleton influence on infant development: a national birth cohort study.
AB  - BACKGROUND: While studying the development of twins, gestational age and
      birthweight were suggested as two of the major mediators to be considered. In
      addition, maternal age, maternal education, parental income and assisted
      reproductive technologies (ART) also should be considered as moderators. Thus the
      purpose of this study was to investigate the mediators and moderators of twin and
      singleton development. METHODS: Being a national birth cohort study, 21 648
      infants were randomly selected and developmental measures were assessed at 6 and
      18 months post partum. Children's development at 6 and 18 months were measured
      using the high reliable Taiwan Birth Cohort Study instrument, which measures
      children's development in four domains of gross motor, fine motor, language and
      social development. Additionally, maternal sociodemographics including maternal
      age, maternal education and parental income; children's characteristics including
      gender, birthweight, gestational age, single or multiple births, ART or natural
      conception information were also collected. These data were analysed using a
      three-step multiple linear regression analysis and further validated using
      structural equation modelling. RESULTS: Parental sociodemographics, children
      characteristics and being twin all had effect on children's development.
      Additionally, ART and twin were mediators between maternal age and children's
      development. Mothers aged over 40 were more likely to choose ART, thus increases
      their likelihood of having twins. Additionally, mothers aged over 40 were more
      likely to give birth to premature or low-birthweight babies, regardless if they
      were twin or not. Twins had a higher prevalence of prematurity or low
      birthweight, which also affected their development in all four domains at 6 and
      18 months. Thus prematurity and low birthweight were mediating factors between
      twin and children's development; with these two mediating factors controlled,
      there were no difference between twin and singleton development. CONCLUSIONS: The
      conceptual construct of structural equation modelling showed these factors
      interacted and influenced children's development through multiple pathways.
      Medical intervention may facilitate children's development through prenatal
      growth and premature care.

PMID- 19397605
TI  - Abandoned babies in the UK - a review utilizing media reports.
AB  - BACKGROUND: In the absence of national policy or comprehensive data, the
      phenomenon of abandoned babies is poorly understood in the UK. This study aims to
      use media reports as a resource to collate existing information on abandoned
      babies and to draw conclusions to inform future response. METHODS: An exhaustive
      media search using electronic searches and media monitoring was undertaken to
      glean systematic information on all abandoned babies in the UK from 1998-2005.
      These were matched onto two databases - the UK Crime Statistics and the UK
      Abandoned Children Register in an attempt to align information on infant
      abandonment. Media reports were coded to list gender, survival, age, parental
      finding and circumstantial data. RESULTS: Our figures suggest an average of 16
      babies abandoned yearly, while official sources give conflicting indications
      because of incomplete data gathering and child over-inclusion. Through systematic
      coding of media reports, 124 babies were identified over a 7-year period. Of
      these, 96 (77.4%) were newborns (<1 week old) and 28 (22.6%) were older babies
      (>1 week old). Adjusted logistic regression analysis found the strongest
      predictors of survival were age at abandonment and 'findability'. Newborn babies
      were less likely to survive than older babies (33.7% newborns died vs. 0% older
      babies, P < 0.0001). Babies left in a non-findable location (34%) had a 5.19
      (2.06, 13.11) higher odds of death compared with those to be found. Most babies
      (74%) were abandoned outdoors and only 9.7% were left with a memento. Few
      mothers, almost exclusively those of older babies, were found (37.1%). Of those
      found, 92% were located within 3 days of abandoning their baby. Media interest is
      transient - 44.8% cases have a single report - and are typified by negative
      headlines (81.5%). CONCLUSIONS: This database currently represents the most
      accurate and comprehensive picture of the newborn abandonment phenomenon in the
      UK, a phenomenon that is rare but with high media and social interest. If the
      future well-being of mother and baby are to be catered for, clearer evidence
      based policy and provision is vital.

PMID- 19397616
TI  - Skin sensitizing properties of the ethanolamines mono-, di-, and triethanolamine.
      Data analysis of a multicentre surveillance network (IVDK) and review of the
      literature.
AB  - Numerous publications address the skin sensitizing potential of the short chain
      alkanolamines triethanolamine (TEA), diethanolamine (DEA), monoethanolamine
      (MEA), which are not skin sensitizing according to animal studies. Regarding TEA,
      we analysed patch test data of 85,098 patients who had been tested with TEA 2.5%
      petrolatum by Information Network of Departments of Dermatology (IVDK) to
      identify particular exposures possibly associated with an elevated risk of
      sensitization. Altogether, 323 patients (0.4%) tested positive. The profile of
      patch test reactions indicates a slightly irritant potential rather than a true
      allergic response in many cases. Although used widely, no exposure associated
      with an increased risk of TEA sensitization was identified. Therefore, the risk
      of sensitization to TEA seems to be very low. MEA and DEA were patch tested in a
      much more aimed fashion in 9602 and 8791 patients, respectively when prevalence
      of contact allergy was 3.8% and 1.8%. MEA is the prominent allergen in
      metalworkers with exposure to water-based metalworking fluids (wbMWFs); DEA is
      probably used in cutting fluids less frequently nowadays. Chronic damage to the
      skin barrier resulting from wbMWF, the alkalinity of ethanolamines (increasing
      from TEA to MEA), and other cofactors may contribute to a notable sensitization
      risk.

PMID- 19397617
TI  - Metalworking exposures and persistent skin symptoms in the ECRHS II and SAPALDIA
      2 cohorts.
AB  - BACKGROUND: Diseases of the skin are important and often preventable conditions
      occurring among workers with dermal exposures to irritant and sensitizing agents.
      OBJECTIVE: We conducted this analysis to assess the associations between
      metalworking exposures and current and persistent skin symptoms among male and
      female participants in two population-based epidemiologic studies. METHODS: We
      pooled data from the European Community Respiratory Health Survey II (ECRHS II)
      and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults
      2 (SAPALDIA 2), two prospective cohort studies in Europe. Each participant
      completed interviewer-administered questionnaires to provide information about
      symptoms and exposures related to selected occupations, including metalworking,
      during the follow-up periods. We assessed associations between skin symptoms and
      the frequency of metalworking exposures among 676 ECRHS II/SAPALDIA 2
      respondents. RESULTS: Current skin symptoms were reported by 10% of metalworkers
      and were associated with frequent use, defined as four or more days per week, of
      oil-based metalworking fluids [prevalence ratio (PR): 1.76, 95% confidence
      interval (CI): 1.25-2.49)] and organic solvent/degreasing agents (PR: 2.06, 95%
      CI: 1.21-3.50). CONCLUSIONS: Skin symptom prevalence is associated with
      increasing frequency of oil-based metalworking fluid and degreasing agent use.
      Our findings justify assessing strategies for reducing the frequency of metal
      related exposures.

PMID- 19397618
TI  - Contact hypersensitivity and allergic contact dermatitis among school children
      and teenagers with eczema.
AB  - BACKGROUND: Patch testing is an essential procedure in the investigation of
      eczema in children. OBJECTIVES: To analyse the frequency of contact
      hypersensitivity and allergic contact dermatitis among Polish children with
      eczema. PATIENTS/METHODS: During an allergy screening programme involving 9320
      children aged 7 and 16 years, 12.6% reported symptoms of chronic/recurrent
      eczema. From this group, a representative sample of 229 eczema children underwent
      patch testing: 96 children aged 7 years and 133 teenagers aged 16 years. Patch
      testing was with 10 allergens: methylchloroisothiazolinone/methylisothiazolinone
      (MCI/MI), nickel sulfate, mercury ammonium chloride, thimerosal, cobalt chloride,
      potassium dichromate, lanolin, fragrance mix I, Myroxylon pereirae (balsam of
      Peru), and colophonium. RESULTS: 49.4% tested children were found patch test (PT)
      positive. 43.8% of 7 year olds with eczema were PT positive, with sensitization
      to nickel sulfate (30.2%), thimerosal (10.4%), cobalt chloride (8.3%), fragrance
      mix I (7.3%), MCI/MI (6.3%), potassium dichromate (6.3%), M. pereirae (3.1%),
      mercury ammonium chloride (2.3%), and colophonium (1.0%). 52.6% teenagers were PT
      positive, with sensitization to nickel sulfate (23.3%), thimerosal (27.8%),
      cobalt chloride (10.5%), potassium dichromate (6.0%), mercury ammonium chloride
      (2.3%), M. pereirae (1.5%), and MCI/MI (0.8%). The final diagnosis of allergic
      contact dermatitis was confirmed in 36% of 7 year olds and 26% of 16 year olds.
      CONCLUSIONS: Every second child with eczema is PT positive, whereas every third
      child is finally diagnosed with allergic contact dermatitis.

PMID- 19397619
TI  - Patch testing of patients allergic to Disperse Blue 106 and Disperse Blue 124
      with thin-layer chromatograms and purified dyes.
AB  - BACKGROUND: Former investigations have demonstrated that patch test preparations
      containing Disperse Blue (DB) 106 and DB 124 are impure. OBJECTIVE: To
      investigate the significance of impurities in preparations of disperse dyes with
      regard to contact allergy. MATERIALS/METHODS: 21 patients allergic to DB 106
      and/or DB 124 were tested with dilution series of commercial and purified DB 106
      and DB 124. All patients were additionally tested with thin-layer chromatography
      (TLC) strips made from the commercial preparations containing DB 106 and 18 of
      them also with TLC strips containing DB 124. RESULTS: 13 of 21 and 12/18 patients
      tested positively to the strips of DB 106 and DB 124, respectively. Among these
      patients, 4/13 and 5/12, respectively, did not react to the main spot but reacted
      to other spots. Dilution series of purified DB 106 and DB 124 were positive in 10
      patients each, while 16 and 15 patients, respectively, tested positively to the
      dilution series of the corresponding commercial disperse dye. CONCLUSION:
      Approximately 25% of the patients, diagnosed as contact allergic to DB 106 and DB
      124, only reacted to impurities in the patch test preparations. This has
      implications for diagnosis and prevention.

PMID- 19397620
TI  - Contact allergy in chronic leg ulcers: results of a multicentre study carried out
      in 423 patients and proposal for an updated series of patch tests.
AB  - BACKGROUND: There is a lack of prospective studies investigating contact
      sensitization in patients with chronic leg ulcers. OBJECTIVES: To determine the
      frequency of contact sensitization in patients with chronic leg ulcers using a
      special series of patch tests and to determine whether the number of
      sensitizations was correlated with the duration of the chronic leg ulcers.
      PATIENTS/METHODS: Multicentre study carried out in patients with chronic leg
      ulcers; patch tests with the European baseline series and with an additional 34
      individual allergens or mixes and 3 commercial products. RESULTS: Of the 423
      patients (301 women, 122 men, mean age 68.5 years) with chronic leg ulcers, 308
      (73%) had at least one positive patch test with 3.65 positive patch tests per
      patient. The main allergens were Myroxylon pereirae (41%), fragrance mix I
      (26.5%), antiseptics (20%), and corticosteroids (8%). The number of positive
      tests per patient was not correlated with the cause of ulcer but was increased
      with the duration of the ulcer with a statistical difference between the group of
      the <1 year compared with the group >10 years duration. CONCLUSIONS: From this
      large prospective multicentre study, polysensitization is frequent in patients
      with chronic leg ulcers, increasing with the duration of the ulcer. We propose
      avoidance of topical antiseptics and ointments containing perfumes in patients
      with chronic leg ulcers and an updated patch test series for investigating these
      patients.

PMID- 19397621
TI  - Identifying the optimal patch test concentration for methylchloroisothiazolinone
      and methylisothiazolinone.

PMID- 19397622
TI  - Nail-fold contact dermatitis from coffee powder.

PMID- 19397623
TI  - Contact dermatitis to self-tanning products.

PMID- 19397624
TI  - Allergic contact dermatitis to hearing aids: literature and case reports.

PMID- 19397625
TI  - Occupational contact dermatitis from golden shrimp plant (Pachystachys lutea).

PMID- 19397626
TI  - Allergic contact cheilitis from D & C Yellow 11.

PMID- 19397627
TI  - Allergic contact dermatitis from dichlorobenzyl alcohol in a patient with
      multiple contact allergies.

PMID- 19397628
TI  - Occupational immediate-type contact allergy to didecyl methyl polyoxyethyl
      ammonium propionate.

PMID- 19397629
TI  - Allergic contact dermatitis from occupational exposure to dibutyl maleate.

PMID- 19397630
TI  - Metal sensitivity to Elektra prostheses - two cases from a metal on metal implant
      for hand joint replacement.

PMID- 19397632
TI  - Randomized controlled clinical trial of customized zirconia and titanium implant
      abutments for canine and posterior single-tooth implant reconstructions:
      preliminary results at 1 year of function.
AB  - OBJECTIVES: The aim of this study was to test whether or not customized zirconia
      abutments exhibit the same survival rates in canine and posterior regions as
      titanium abutments, and to compare the esthetic result of the two abutment types.
      MATERIAL AND METHODS: Twenty-two patients with 40 implants in posterior regions
      were included and the implant sites were randomly assigned to 20 customized
      zirconia and 20 customized titanium abutments. All-ceramic (AC) and metal-ceramic
      (MC) crowns were fabricated. In all except two cases, the crowns were cemented on
      the abutments using resin or glass-ionomer cements. Two zirconia reconstructions
      were screw retained. At baseline, 6 and 12 months, the reconstructions were
      examined for technical and biological problems. Probing pocket depth (PPD),
      plaque (Pl) and bleeding on probing (BOP) were assessed and compared with natural
      control teeth. Furthermore, the difference of color (DeltaE) of the peri-implant
      mucosa and the gingiva of control teeth was evaluated by means of a
      spectrophotometer (Spectroshade). The data were analyzed with Student's unpaired
      t-test, ANOVA and regression analyses. RESULTS: Twenty patients with 19 zirconia
      and 12 titanium abutments were examined at a mean follow-up of 12.6+/-2.7 months.
      The survival rate for reconstructions and abutments was 100%. No technical or
      biological problems were found at the test and control sites. Two chippings
      (16.7%) occurred at crowns supported by titanium abutments. No difference was
      found regarding PPD (meanPPD(ZrO2) 3.4+/-0.7 mm, mPPD(Ti) 3.3+/-0.6 mm), Pl
      (mPl(ZrO2) 0.2+/-0.3, mPl(Ti) 0.1+/-1.8) and BOP (mBOP(ZrO2) 60+/-30%, mBOP(Ti)
      30+/-40%) between the two groups. Both crowns on zirconia and titanium abutments
      induced a similar amount of discoloration of the soft tissue compared with the
      gingiva at natural teeth (DeltaE(ZrO2) 8.1+/-3.9, DeltaE(Ti) 7.8+/-4.3).
      CONCLUSIONS: At 1 year, zirconia abutments exhibited the same survival and a
      similar esthetic outcome as titanium abutments.

PMID- 19397633
TI  - Subcrestal placement of two-part implants.
AB  - OBJECTIVE: The aim of the present experiment was to study the healing around two
      part implants that were placed in a subcrestal position. MATERIAL AND METHODS:
      Five mongrel dogs, about 2 years old, were included. The mandibular premolars and
      the first, second and third maxillary premolars were extracted. Three months
      later two test and two control implants (OsseoSpeed, 3.5 mm x 8 mm) were placed
      in one side of the mandible. The implants were placed in such a way that the
      implant margin was located 2 mm apical to the bone crest. In the test implants,
      the surface modification extended to the implant margin and, thus, included the
      shoulder part of the implant. Regular abutments with a turned surface (Zebra)
      were connected to the control implants, while experimental abutments with a
      modified surface (TiOblast) were connected to the test implants. A plaque control
      program that included cleaning of implants and teeth every second day was
      initiated. Four months later the dogs were euthanized and biopsies were obtained
      and prepared for histological analysis. RESULTS: The marginal bone level at the
      test implants was identified in a more coronal position than that at the control
      implants. In 40% of the test implants, the bone-to-implant contact extended
      coronal of the abutment/fixture (A/F) border, i.e. in contact with the abutment
      part of the implant. The connective tissue portion of the peri-implant mucosa
      that was facing the test abutments contained a higher density of collagen and a
      smaller proportion of fibroblasts than that at the control sites. CONCLUSION: It
      is suggested that osseointegration may occur coronal to the A/F interface of two
      part implants. Such a result, however, appears to depend on the surface
      characteristics of the implant components.

PMID- 19397634
TI  - A study of the bone healing kinetics of plateau versus screw root design titanium
      dental implants.
AB  - OBJECTIVE: This study was designed to compare the bone healing process around
      plateau root from (PRF) and screw root from (SRF) titanium dental implants over
      the immediate 12 week healing period post implant placement. MATERIAL AND
      METHODS: 32PRF and 32SRF implants were placed in 8 beagle dogs at 12, 8, 5 and 3
      weeks prior to enthanisation using a bilaterally balanced distribution.
      Undecalcified ground sections were prepared from the biopsies taken and
      histometric measurements of bone implant contact (BIC) and bone area fraction
      occupancy (BAFO) were made on the middle 5 mm portion of each 8 mm implant root
      length. RESULTS: The analysis showed that although measurements of bone to
      implant contact (BIC) and bone area fraction occupancy (BAFO) tended to be
      greater for the SRF implants at all four time points, the differences in
      measurements between implant types did not reach statistical significance
      (P=0.07, P=0.06). The effect of time on BIC and BAFO was found to be strongly
      significant for both implant types thus indicating a statistically significant
      increase in BIC and BAFO overall with time (P=0.004, P=0.002). Furthermore, both
      PRF and SRF implants behaved similarly over time with measurements of BIC and
      BAFO progressing in parallel. Histomorphologic analysis of these sections
      demonstrated the prominent role of woven bone (callus) in the bone healing
      process around PRF implants. CONCLUSION: The results can be interpreted to
      indicate a comparable development of secondary stability for both PRF and SRF
      implant designs. However, as these parameters reflect the structural connection
      between implant and bone and not the functional properties of the bone to implant
      interface, they cannot be regarded as comprehensive measures of osseointegration.
      This particularly relevant given the reduced load bearing capacity of woven bone.

PMID- 19397635
TI  - Development of the osteoblastic phenotype in human alveolar bone-derived cells
      grown on a collagen type I-coated titanium surface.
AB  - OBJECTIVE: The aim of this study was to evaluate the development of the
      osteoblastic phenotype in human alveolar bone-derived cells grown on collagen
      type I-coated titanium (Ti) surface (Col-Ti) obtained by plasma deposition
      acrylic acid grafting compared with machined Ti (M-Ti). MATERIAL AND METHODS:
      Osteoblastic cells were cultured until subconfluence and subcultured on Col-Ti
      and M-Ti for periods of up to 21 days. RESULTS: Cultures grown on Col-Ti and M-Ti
      exhibited similar cell morphology. Cell adhesion, total protein content, and
      alkaline phosphatase (ALP) activity were not affected by Ti surface modification
      in all evaluated periods. Growth analyses indicated that there were significantly
      more cells in cultures grown on Col-Ti at day 3. Runt-related transcription
      factor 2 (Runx2), osteopontin (OPN), and osteoprotegerin (OPG) mRNA expression of
      cells subcultured on Col-Ti was higher, whereas collagen type I (COL) was lower
      compared with M-Ti. Ti surface modification neither affected the osteocalcin
      (OC), ALP and receptor activator of NF-kappaB ligand (RANKL) mRNA expression nor
      the calcium content extracted from mineralized matrix. CONCLUSIONS: These results
      demonstrated that Col-Ti favours cell growth during the proliferative phase (day
      3) and osteoblastic differentiation, as demonstrated by changes in mRNA
      expression profile during the matrix mineralization phase (day 14), suggesting
      that this Ti surface modification may affect the processes of bone healing and
      remodelling.

PMID- 19397636
TI  - Bone apposition around two different sandblasted, large-grit and acid-etched
      implant surfaces at sites with coronal circumferential defects: an experimental
      study in dogs.
AB  - OBJECTIVE: The study was designed to evaluate bone apposition around SLA
      (sandblasted, large-grit and acid-etched) implants compared with modified SLA
      (modSLA) ones at sites with different sizes of circumferential gaps. MATERIAL AND
      METHODS: All mandibular premolars and first molars of six beagle dogs were
      extracted. After a healing period of 3 months, three 10-mm-long implants were
      inserted in each side of the mandible. One implant was inserted with a 0.5-mm and
      one with a 1-mm gap between the implants and bone around the coronal 5 mm of the
      implants. The third implant was inserted without a gap as a control. The dogs
      were sacrificed respectively at weeks 2, 4 and 8 after implant placement for
      histological and histomorphometric analyses. RESULTS: The histomorphometric
      results showed similar pattern of bone apposition for the two surfaces. At 2 and
      4 weeks of healing, the percentage of newly formed bone-to-implant contact
      (BIC%), new bone fill (NBF%) and the distance between the most coronal position
      of BIC and the defect bottom (B-D) were significantly higher for modSLA (P<0.05).
      At 8 weeks of healing, this difference was not significant (P>0.05). With regard
      to the defect size, the histological analyses showed no significant differences
      between the two defect sizes at all time points (P>0.05). CONCLUSION:
      Significantly more bone apposition was found for the modSLA surface than for the
      SLA surface at early stage of healing, indicating that modSLA surface may enhance
      bone apposition in coronal circumferential defects at non-submerged implants. Gap
      size within 1 mm may not need any kind of regenerative procedures.

PMID- 19397637
TI  - Prospective clinical evaluation of 1920 Morse taper connection implants: results
      after 4 years of functional loading.
AB  - PURPOSE: This study evaluated the survival rate and the clinical, radiographic
      and prosthetic success of 1920 Morse taper connection implants. MATERIAL AND
      METHODS: One thousand nine hundred and twenty Morse taper connection implants
      were inserted in 689 consecutive patients, from January 2003 until December 2006.
      Implants were clinically and radiographically evaluated at 12, 24, 36 and 48
      months after insertion (mean follow-up per implant: 25.42 months). Modified
      plaque index (mPI), modified sulcus bleeding index, probing depth (PD) and the
      distance between implant shoulder and first crestal bone-implant contact (DIB)
      were measured in mm. Success criteria included the absence of suppuration and
      clinically detectable implant mobility, PD<5 mm, DIB<1.5 mm after 12 months of
      functional loading and not exceeding 0.2 mm for each following year, the absence
      of recurrent prosthetic complications at the implant-abutment interface.
      Prosthetic restorations were fixed partial prostheses (364 units), single crowns
      (SCs: 307 units), fixed full-arch prostheses (53 units) and overdentures (67
      units). RESULTS: The overall cumulative implant survival rate was 97.56% (96.12%
      in the maxilla and 98.91% in the mandible). The cumulative implant success rate
      was 96.61% (95.25% in the maxilla and 98.64% in the mandible). Only a few
      prosthetic complications were reported (0.65% of loosening at implant-abutment
      interface in SCs). CONCLUSION: The use of Morse taper connection implants
      represents a successful procedure for the rehabilitation of partially and
      completely edentulous arches. The absence of an implant-abutment interface
      (microgap) is associated with minimal crestal bone loss. The high mechanical
      stability significantly reduces prosthetic complications.

PMID- 19397638
TI  - Surface microgrooves and acid etching on titanium substrata alter various cell
      behaviors of cultured human gingival fibroblasts.
AB  - OBJECTIVE: This study aimed to investigate the influence of surface microgrooves
      and acid etching on titanium substrata on cell proliferation and gene expression
      of cultured human gingival fibroblasts. MATERIAL AND METHODS: Ti substrata with
      various dimensions of microgrooves and further acid etching comprised four
      experimental groups (E15/3.5, E30/5, E60/10, and E90/15), whereas smooth and acid
      etched Ti discs were both used as control (NE0 and E0). The chemical composition
      of the control and experimental cp Ti substrata was analyzed by X-ray
      photoelectron spectroscopy (XPS). Cell proliferation, gene expression, and
      protein expression of cultured human gingival fibroblasts were analyzed between
      all groups using bromodeoxyuridine (BrdU) assay, reverse-transcriptase polymerase
      chain reaction (RT-PCR), and Western blotting, respectively. RESULTS: The XPS
      results showed that the Ti substrata used in this study showed no significant
      differences in the expression of surface chemical composition. BrdU assay showed
      that cell proliferation was significantly increased in E60/10 compared with that
      in any other group. In RT-PCR, E60/10 was noted to increase the expression of
      various genes involved in cell-matrix adhesion and adhesion-dependent cell cycle
      progression. In Western blotting, increased expression of fibronectin and Rho A
      was noted in E60/10 compared with that in NE0 or E15/3.5. CONCLUSION: This study
      indicates that surface microgrooves 60 mum in width and 10 mum in depth, and
      further acid etching on Ti substrata trigger the proliferation and alter the
      expression of both genes and proteins in cultured human gingival fibroblasts.

PMID- 19397639
TI  - Effects of the combination with alpha-tricalcium phosphate and simvastatin on
      bone regeneration.
AB  - BACKGROUND: Although local application of statins stimulates bone formation, high
      dose of simvastatin induces inflammation. OBJECTIVE: A study was conducted to
      test the hypothesis that maximum bone regeneration with less inflammation would
      be achieved by combining an optimal dose of simvastatin with alpha-tricalcium
      phosphate (alpha-TCP), which is an osteoconductive biomaterial capable of
      releasing the drug gradually. MATERIAL AND METHODS: Bilateral 5-mm-diameter
      calvarial defects were created in adult Wistar rats and filled with preparations
      of different doses of simvastatin (0, 0.01, 0.1, 0.25 and 0.5 mg) combined with
      alpha-TCP particles or left empty. The animals were sacrificed at 2, 4 and 8
      weeks and analyzed radiologically and histologically. Half of the animals of 4
      and 8 weeks were labeled with fluorescence dyes and histomorphometrically
      analyzed. RESULTS: Simvastatin doses of 0.25 and 0.5 mg caused inflammation of
      the soft tissue at the graft site whereas control and other doses did not. The
      micro-CT analysis revealed that the alpha-TCP with 0.1 mg simvastatin (TCP-0.1)
      group yielded significantly higher bone volumes than untreated control group at
      all three time points (249%, 227% and 266% at 2, 4 and 8 weeks, respectively).
      The percentage of defect closure, bone mineral content and bone mineral density
      were also higher in the TCP-0.1 group than in the other groups. CONCLUSION: When
      combined with alpha-TCP particles, 0.1 mg simvastatin is the optimal dose for
      stimulation of the maximum bone regeneration in rat calvarial defects without
      inducing inflammation and it could be applied as an effective bone graft
      material.

PMID- 19397640
TI  - Bioactivation of alumina by surface modification: a possibility for improving the
      applicability of alumina in bone and oral repair.
AB  - OBJECTIVES: In regenerative medicine, surface engineering of bioinert synthetic
      materials is often required in order to introduce bioactive species that can
      promote cell adhesion, proliferation, viability and enhanced ECM-secretion
      functions. The aim of this work is to study cell interaction with alumina
      modified surfaces. MATERIAL AND METHODS: In this work, chemical properties of
      alumina surface were changed by a reaction at the surface of alumina with low
      molecular weight dicarboxylic acid, which produced carboxyl groups. RESULTS:
      These carboxyl groups were able to complex with Ca2+ on the surface, forming
      sites of precipitation for calcium phosphates that make alumina biocompatible, as
      indicated by cell culture of pre-osteoblasts (MC3T3-E1 cell line). CONCLUSIONS:
      The procedure presented in this work shows that the insertion of specific
      functional groups on the surface of alumina increases cell interaction with the
      surface of alumina. This knowledge can be important in oral science and
      orthopedics, for the construction of prosthesis.

PMID- 19397641
TI  - Effects of irrigation temperature on heat control in vitro at different drilling
      depths.
AB  - PURPOSE: Thermal injury during implant bed preparation has a major influence on
      implant osseointegration and survival. This study investigated the effectiveness
      of the temperature of the saline solution used for heat control during drilling.
      MATERIAL AND METHODS: Fresh frozen edentulous segments of bovine mandibles were
      sectioned into 12 x 6 cm pieces. Thermoresistors were placed 0.5 mm from the
      drilling cavity walls, at depths of 3, 7, and 12 mm. Signals from the three
      thermoresistors were analyzed using ORIGIN 5.0 software. RESULTS: The maximum
      temperatures during drilling without irrigation were 50.9, 47.4, and 38.1 degrees
      C at depths of 3, 7, and 12 mm, respectively. With irrigation using saline at 25
      and 10 degrees C, the maximum temperatures at a depth of 12 mm were 37.4 and 36.3
      degrees C, respectively. All other measurements with both 25 and 10 degrees C
      saline were below body temperature. DISCUSSION AND CONCLUSION: This experimental
      in vitro study showed that more heat was generated in the superficial part of the
      drilling cavity than at the bottom. Therefore, external irrigation at room
      temperature can provide sufficient cooling during drilling. Lower temperature
      saline was more effective in cooling the bone, and irrigation of the site should
      be continued between the drilling steps.

PMID- 19397642
TI  - Ultrastructural study of tissues surrounding replanted teeth and dental implants.
AB  - OBJECTIVES: The aim of this study was to describe the ultrastructure of the
      dentogingival border at replanted teeth and implants. MATERIAL AND METHODS:
      Wistar rats (8 weeks old) were divided into groups for replantation and
      implantation experiments. In the former, the upper right first molars were
      extracted and then immediately replanted. In the latter, pure titanium implants
      were used. All tissues were fixed, demineralized and embedded in epoxy resin for
      ultrastructural observations. RESULTS: One week after replantation, the
      junctional epithelium was lost, and the oral sulcular epithelium covered the
      enamel surface. The amount of the epithelium increased in 2 weeks, and resembled
      the junctional epithelium, and the internal basal lamina and hemidesmosomes were
      formed in 4 weeks. One week after implantation, peri-implant epithelium was
      formed, and in 2 and 4 weeks, this epithelium with aggregated connective tissue
      cells were observed. In 8 weeks, the peri-implant epithelium receded, and aligned
      special cells with surrounding elongated fibroblasts and bundles of collagen
      fibers appeared to seal the implant interface. CONCLUSION: In replantation of the
      tooth, the internal basal lamina remained at the surface of the enamel of the
      replanted tooth, which is likely to be related to regeneration of the junctional
      epithelium and the attachment apparatus at the epithelium-tooth interface.
      Following implantation, a layer of cells with characteristics of connective
      tissue cells, but no junctional epithelium and attachment apparatus, was formed
      to seal the site of the implant.

PMID- 19397643
TI  - Which region of the median palate is a suitable location of temporary orthodontic
      anchorage devices? A histomorphometric study on human cadavers aged 15-20 years.
AB  - INTRODUCTION: Endosseus implants can provide a reliable anchorage during
      orthodontic treatment. The midpalatal structures around the sutura palatina
      mediana (SPM) are of special interest due to increasing placement of orthodontic
      implants in this area. Knowledge about the osseous conditions at this site is
      necessary to predict the expected degree of implant osseointegration. METHODS:
      The upper jaws of 10 human cadavers, aged 15-20 years, were decalcified, and
      cross-sectional specimens were obtained from four anterior-to-posterior palatal
      regions for histomorphometric analysis. The analyses focused on the amount of
      bone and the width of the SPM to determine the anatomical requirements for
      reliable insertion of palatal implants. RESULTS: Bone density [bone-volume (BV)/
      tissue-volume (TV)] in all measured areas was 40-60%. The maximum density was
      measured at the level of the first premolars (54.9+/-5.9%) and the least values
      (44.2+/-9.6%) were measured at the level of the interconnecting line of the
      canines. The mean width of the SPM varies from 1.2 to 0.3 mm in different
      sections of the palate. In the median sagittal plane, the mean values of bone
      height to nasal cavity reached >5 mm as far as the level distal of the second
      premolars. Bone height 2 mm paramedian to the SPM decreased consistently from
      anterior (4.3+/-0.9 mm) to posterior (2.5+/-0.8 mm). CONCLUSIONS: Our results
      indicate that the amount and quality of bone along the anterior palatal midline
      in 15-to-20-year olds is sufficient for orthodontic implantation. Even
      implantation posterior to the recommended first premolar level, at which
      orthodontic implants are most often placed, may be suitable. There are some
      limitations, however, due to small number of samples and variations of anatomical
      structures.

PMID- 19397644
TI  - A prospective randomized split-mouth study comparing iliac onlay grafts in
      atrophied edentulous patients: covered with periosteum or a bioresorbable
      membrane.
AB  - PURPOSE: In this prospective study, solid monocortical iliac onlay grafts of the
      maxilla were randomly covered with a bioresorbable membrane and periosteum within
      the maxilla. Histologic specimens were analyzed by light microscopy after a
      healing period of three months and the rate of resorption of the grafts were
      measured. MATERIALS AND METHODS: Fourteen patients (9 females and 5 males), with
      a mean age of 56 years (range 25-72) underwent augmentation with avascular iliac
      onlay bone grafts. The grafts were randomly covered either with a bioresorbable
      membrane (MC) or periosteum (PC). Resorption was measured with a digital caliper
      at the microscrews (slashed circle 1.5 mm) used to fixate the graft. Histologic
      evaluation of the specimens derived from the graft with a trephine bur (slashed
      circle 2 mm) from the implant site at implant placement after a 3-month healing
      period. Statistical evaluation of the data was performed using Analysis of
      variance and the Wilcoxon signed rank test. RESULTS: Clinical appearance of the
      augmented bone after 3 months showed a dense cortical layer with good vascular
      perfusion. Thirty-three sites in 13 patients (one dropped put) were analyzed
      histomorphometrically and showed an average of 46% newly formed bone with no
      significant difference between the groups (P=0.46). The mean resorption rate at
      56 measured sites was 1.2 mm (range 0.3-3.4 mm) after 3 months, with no
      significant difference between the MC sites and the PC sites (P=0.38).
      DISCUSSION: Histomorphometry of new bone formation after 3 months demonstrates no
      significant difference between the PC and MC groups. Initialization of graft
      resorption can be seen after 3 months with no significant difference as to
      whether the graft was covered with a membrane or the periosteum. CONCLUSION: This
      study provides evidence that after avascular iliac bone grafting, the
      revascularization of the graft was sufficient after 3 months regardless of the
      graft coverage with no effect on the amount of initial resorption of the graft.

PMID- 19397645
TI  - Blind multicenter study of the efficacy and safety of injections of a commercial
      preparation of botulinum toxin type A reconstituted up to 15 days before
      injection.
AB  - BACKGROUND: It is recommended that attention be given to the shelf life of
      botulinum toxin type A (BT-A) after its reconstitution. OBJECTIVE: To assess the
      efficacy and safety of 500 U of BT-A after reconstitution up to 15 days after
      injection. MATERIAL AND METHODS: BT-A vials were diluted 15 days, 8 days, and 8
      hours before injection. One hundred five volunteers were randomized to one of
      three treatment groups, according to dilution dates. They were evaluated at
      baseline and 28, 56, 84, and 112 days after treatment. At each visit, the
      investigator and the volunteer evaluated the motility of the treated area using a
      4-point qualitative scale. Five independent specialists, who scored the motility
      of the treated area on the same scale, blind analyzed photographs taken at each
      visit. The reconstituted vials of BT-A were stored and analyzed before and after
      the study. RESULTS: No significant difference was shown between the groups. No
      evidence of contamination was found in the BT-A vials. CONCLUSION: The results
      confirm the possibility of injecting 500 U of BT-A up to 15 days after its
      reconstitution safely and without loss of efficacy.

PMID- 19397646
TI  - Skin rejuvenation with 1,064-nm Q-switched Nd:YAG laser in Asian patients.
AB  - BACKGROUND: In recent years, using the 1,064-nm Q-switched neodymium-doped
      yttrium aluminium garnet (Nd:YAG) laser (QSNYL) with or without exogenous topical
      carbon solution application for facial skin rejuvenation has become popular in
      Southeast Asia, but there has not been any published clinical report discussing
      the rejuvenation effect of QSNYL for Asian patients. OBJECTIVE: To evaluate the
      efficacy of QSNYL in improvement of pore size, sebaceous secretion, skin texture,
      and skin tone of Asian patients. We also observed whether there is any
      enhancement of application of topical carbon solution before the therapy.
      METHODS: Twenty-four female patients completed four sessions of treatments at 4
      week intervals. The assessment was evaluated by the patients, two independent
      physicians, and Canfield VISIA Complexion Analysis. In addition, we conducted a
      split-face study such that, in each case, topical carbon solution was applied to
      the right side of the face before the laser treatment. RESULTS: All evaluations
      showed significant improvement in rejuvenation effect. There was no difference in
      improvement in skin texture even after the application of topical carbon solution
      in our split-face study. CONCLUSION: The QSNYL is a safe and effective
      rejuvenation modality in Asian patients. Topical carbon solution application did
      not enhance laser efficacy.

PMID- 19397647
TI  - Immunohistochemical stains in Mohs surgery: a review.
AB  - BACKGROUND: During Mohs surgery, there are instances in which residual tumor
      cells may be difficult to detect, thereby increasing the risk of incomplete
      excision and tumor recurrence. It is possible to employ immunohistochemical
      techniques as an adjunct to routine hematoxylin and eosin staining to aid in
      ensuring negative margins. OBJECTIVE: To review the literature regarding the use
      of immunostains in Mohs surgery. RESULTS: Various immunostains have proved useful
      in detecting tumor cells in various malignancies, including melanoma, basal cell
      carcinoma, squamous cell carcinoma, dermatofibrosarcoma protuberans, extramammary
      Paget's disease, primary cutaneous mucinous carcinoma, granular cell tumor, and
      trichilemmal carcinoma. CONCLUSIONS: In this article, we review
      immunohistochemical stains that have been employed in Mohs micrographic surgery
      and evaluate their utility in enhancing detection of residual tumors with respect
      to tumor type, particularly in situations in which detection of residual tumor
      may be difficult.

PMID- 19397648
TI  - Re: Subdermal Nd-YAG laser for axillary hyperhidrosis.

PMID- 19397649
TI  - Multiple eccrine hidrocystomas--response to treatment with carbon dioxide and
      pulsed dye lasers.

PMID- 19397650
TI  - Comment on Tamura et al's Allergic reaction to botulinum toxin: positive
      intradermal test.

PMID- 19397651
TI  - Recipient-site influence in hair transplantation: a confirmative study.

PMID- 19397652
TI  - Identifying a tissue floater on Mohs frozen sections.

PMID- 19397653
TI  - Risk of ablative therapy for "elevated firm growing" lesions: Merkel cell
      carcinoma diagnosed after laser surgical therapy.

PMID- 19397654
TI  - Reconstruction of a chondrocutaneous auricular defect using a Kirschner wire.

PMID- 19397655
TI  - Adenoid cystic carcinoma of the eyelid: a rare cutaneous tumor treated with Mohs
      micrographic surgery.

PMID- 19397656
TI  - New method alternative to surgery for ingrown nail: angle correction technique.

PMID- 19397657
TI  - Combined 595-nm and 1,064-nm laser irradiation of recalcitrant and hypertrophic
      port-wine stains in children and adults.
AB  - PURPOSE: Although pulsed dye laser (PDL) treatment of port-wine stain (PWS) has
      long been proven safe and effective, incomplete clearance of these vascular
      malformations can be problematic. In addition, advanced PWS with deeper
      coloration and tissue hypertrophy can be particularly difficult to treat because
      of the superficial dermal penetration of 585- to 595-nm light. The purpose of
      this study was to evaluate the safety and efficacy of a novel device that
      delivers sequential pulses of 595- and 1,064-nm wavelengths in the treatment of
      recalcitrant and hypertrophic PWS. METHODS: Twenty-five children and adults (skin
      phototypes I-III) with recalcitrant or hypertrophic PWS showing incomplete
      clearance after 10 prior PDL treatments were included in the study. Successive
      treatments using a 595-nm PDL and a 1,064-nm neodymium-doped yttrium-aluminum
      garnet (Nd:YAG) laser were delivered at 6- to 8-week intervals. Two masked
      assessors determined clinical improvement of treatment areas using independent
      evaluation of comparative photographs at baseline and 3 months after treatment
      using a standard quartile grading scale. RESULTS: The use of dual 595-/1,064-nm
      wavelengths provided continued improvement of PWS that were previously
      recalcitrant to ongoing PDL therapy. Side effects were limited to transient
      erythema, edema, and mild purpura. Rare vesicle formation was observed, with no
      subsequent scarring or undesirable pigmentary changes. CONCLUSION: The novel dual
      595-nm PDL and 1,064-nm Nd:YAG laser is an effective treatment for PWS that are
      recalcitrant to PDL therapy alone.

PMID- 19397658
TI  - Polyangulated specimen and tissue nicks to facilitate orientation and re-excision
      in Mohs micrographic surgery.

PMID- 19397659
TI  - Partially torn ear lobe repair using a cross-stitching technique.

PMID- 19397660
TI  - Trichloroacetic acid matricectomy in the treatment of ingrowing toenails.
AB  - BACKGROUND: Ingrowing toenails can be treated with conservative therapy or
      surgery, but frequent relapse can be a problem in conservative therapy and
      surgical therapy without matricectomy. Thus, permanent nail ablation by partial
      matricectomy is now accepted as the treatment of choice. OBJECTIVE: To evaluate
      the efficacy and safety of trichloroacetic acid (TCA) matricectomy in the
      treatment of ingrowing nail. MATERIALS AND METHODS: Forty ingrowing toenail edges
      in 25 patients were enrolled. TCA matricectomy with 100% trichloroacetic acid
      after partial nail avulsion was performed. For a few weeks after surgery,
      postoperative complications such as pain, discharge, and infection were assessed.
      After a mean follow-up period of 22.9 months, recurrence rate and cosmetic
      outcomes were investigated to evaluate the effects of the surgery. RESULTS: The
      wounds almost always healed within 2 weeks without prolonged exudative discharge.
      Pain was mild and transient. A case of secondary infection occurred. Recurrence
      was found in only two nails of one patient, and the success rate was 95%, with
      good cosmetic results. CONCLUSION: TCA matricectomy showed a low recurrence rate
      with minimal side effects and was easy to perform in outpatient clinic.
      Therefore, it may be a good alternative treatment of ingrowing toenails.

PMID- 19397661
TI  - Assessment of optical coherence tomography imaging in the diagnosis of non
      melanoma skin cancer and benign lesions versus normal skin: observer-blinded
      evaluation by dermatologists and pathologists.
AB  - BACKGROUND: Optical coherence tomography (OCT) is an optical imaging technique
      that may be useful in diagnosis of non-melanoma skin cancer (NMSC). OBJECTIVES:
      To describe OCT features in NMSC such as actinic keratosis (AK) and basal cell
      carcinoma (BCC) and in benign lesions and to assess the diagnostic accuracy of
      OCT in differentiating NMSC from benign lesions and normal skin. METHODS AND
      MATERIALS: OCT and polarization-sensitive (PS) OCT from 104 patients were
      studied. Observer-blinded evaluation of OCT images from 64 BCCs, 1 baso-squamous
      carcinoma, 39 AKs, two malignant melanomas, nine benign lesions, and 105 OCT
      images from perilesional skin was performed; 50 OCT images of NMSC and 50 PS-OCT
      images of normal skin were evaluated twice. RESULTS: Sensitivity was 79% to 94%
      and specificity 85% to 96% in differentiating normal skin from lesions. Important
      features were absence of well-defined layering in OCT and PS-OCT images and dark
      lobules in BCC. Discrimination of AK from BCC had an error rate of 50% to 52%.
      CONCLUSION: OCT features in NMSC are identified, but AK and BCC cannot be
      differentiated. OCT diagnosis is less accurate than clinical diagnosis, but high
      accuracy in distinguishing lesions from normal skin, crucial for delineating
      tumor borders, was obtained.

PMID- 19397662
TI  - Donor site morbidity of the posterior conchal region.
AB  - BACKGROUND: The perichondral cutaneous graft (PCCG) from the posterior conchal
      region is an elegant solution for the coverage of facial defects with particular
      stability requirements. The donor defect can easily be covered with a
      transposition flap from the postauricular region. Although this region is a
      common donor site for skin grafts and has an important supporting function for
      glasses or hearing aids, little is known about long-term morbidity after graft
      harvest. OBJECTIVE: To assess the morbidity of the posterior concha and the
      postauricular region in terms of pain, scar formation, and patient satisfaction.
      MATERIALS AND METHODS: A retrospective study of 16 patients who had a PCCG
      harvested from the posterior concha. RESULTS: Two patients presented with a
      postoperative wound dehiscence on the postauricular region and one with a keloid
      scar on the posterior concha. One case of transitory hyperesthesia and pain when
      sleeping on the operated site was observed. None had complaints related to
      wearing glasses or hearing aids. CONCLUSION: Donor site morbidity of the
      postauricular and posterior conchal region is minimal and associated with high
      patient satisfaction, excellent aesthetic results, and emotional detachment from
      the hidden donor site.

PMID- 19397663
TI  - Comparing in vivo reflectance confocal microscopy, dermoscopy, and histology of
      clear-cell acanthoma.
AB  - BACKGROUND: Clear cell acanthoma (CCA) is a rare, benign neoplasm of unknown
      etiology, whose dermoscopic and histological features have been previously
      described. Usually, CCA can be diagnosed by clinical and dermoscopic examination.
      In some cases, diagnosis remains uncertain, and histological examination is
      needed. The aim of this paper was to describe the features of reflectance
      confocal microscopy (RCM) in diagnosing CCA, compare them with findings on
      dermoscopy and histology, and evaluate their possible usefulness in CCA
      evaluation. PATIENTS AND METHODS: Five lesions diagnosed clinically as CCA were
      imaged using dermoscopy and RCM. All lesions were surgically excised to confirm
      the diagnosis and compare the morphological attributes under light microscopy
      with in vivo imaging. RESULTS: RCM showed well-circumscribed lesions, often edged
      by a hyperkeratotic collarette with parakeratosis; inflammatory cells in the
      spinous layer; large keratinocytes; acanthosis with papillomatosis; epidermal
      disarray; and dilated capillaries forming glomeruloid shapes in the upper dermis.
      CONCLUSIONS: In this small study, RCM was able to identify most of the
      established diagnostic histological features of CCA. RCM appears to be a useful
      tool for in vivo diagnosis of CCA and may help avoid unnecessary biopsies.

PMID- 19397664
TI  - The influence of a eutectic mixture of lidocaine and prilocaine on minor surgical
      procedures: a randomized controlled double-blind trial.
AB  - BACKGROUND: A eutectic mixture of lidocaine and prilocaine (EMLA) has been shown
      to be effective in reducing pain from needle sticks, including those associated
      with blood sampling and intravenous insertion. OBJECTIVE: To evaluate the
      effectiveness of EMLA cream applied before needle puncture for local anesthetic
      administration before minor surgical procedures in this double-blind, randomized,
      controlled, parallel-group study. MATERIALS AND METHODS: Patients were randomly
      assigned to receive EMLA or placebo cream (Aqueous) applied under an occlusive
      dressing. After the procedure, patients were asked to rate the needle prick and
      procedure pain on a visual analog scale (0=no pain; 10=maximum pain). RESULTS: A
      total of 94 minor surgical procedures (49 in EMLA and 45 in control) were
      performed. The mean needle-stick pain score in the EMLA group was significantly
      lower than in the control group (2.7 vs. 5.7, p<.001, Mann-Whitney U-test). There
      was also significantly lower procedure pain in the EMLA group than in the control
      group (0.83 vs. 1.86, p=.009). There were no complications associated with the
      use of EMLA. CONCLUSION: EMLA effectively reduces the preprocedural needle-stick
      pain and procedural pain associated with minor surgical procedures.

PMID- 19397665
TI  - The use of botulinum toxin in the treatment of a parotid duct injury during Mohs
      surgery and review of management options.
AB  - BACKGROUND: Aggressive skin cancers on the cheeks may involve the parotid duct.
      For such tumors to be successfully removed, at least part of the parotid duct
      must be excised as well. Failure to properly address parotid duct injuries that
      result from Mohs micrographic surgery exposes the patient to a variety of adverse
      sequelae. OBJECTIVE: To discuss the various diagnostic and treatment options that
      should be considered when managing parotid duct injuries that result from skin
      cancer extirpation. MATERIALS AND METHODS: We describe a patient who sustained a
      parotid duct injury after Mohs micrographic surgery for treatment of squamous
      cell carcinoma. The patient was treated with intraparotid injections of botulinum
      toxin. RESULTS: Two weeks after treatment of the injury with botulinum toxin, the
      patient reported complete resolution of his symptoms. CONCLUSION: If a parotid
      duct injury is diagnosed at the time of tumor extirpation, then surgical repair
      of the duct should be attempted, but if surgical repair is not possible or if an
      injury remains unrecognized until well after tumor extirpation, then surgery is
      not necessary. In such cases, conservative, nonsurgical measures, such as
      treatment with botulinum toxin, will provide excellent results.

PMID- 19397666
TI  - Opaque titanium and zinc sunscreen as an effective and versatile masking agent
      during laser hair removal: the batik-masking approach.

PMID- 19397667
TI  - Comparative efficacy of nonpurpuragenic pulsed dye laser and intense pulsed light
      for erythematotelangiectatic rosacea.
AB  - BACKGROUND: Erythematotelangiectatic (ET) rosacea is commonly treated with a
      variety of laser and light-based systems. Although many have been used
      successfully, there are a limited number of comparative efficacy studies.
      OBJECTIVE: To compare nonpurpuragenic pulsed dye laser (PDL) with intense pulsed
      light (IPL) treatment in the ability to reduce erythema, telangiectasia, and
      symptoms in patients with moderate facial ET rosacea. METHODS: Twenty-nine
      patients were enrolled in a randomized, controlled, single-blind, split-face
      trial with nonpurpuragenic treatment with PDL and IPL and untreated control.
      Three monthly treatment sessions were performed with initial PDL settings of 10
      mm spot size, 7 J/cm(2), 6-ms pulse duration and cryogen cooling, and initial IPL
      settings of 560-nm filter, a pulse train of 2.4 and 6.0 ms in duration separated
      by a 15-ms delay, and a starting fluence of 25 J/cm(2). Evaluation measures
      included spectrophotometric erythema scores, blinded investigator grading, and
      patient assessment of severity and associated symptoms. RESULTS: PDL and IPL
      resulted in significant reduction in cutaneous erythema, telangiectasia, and
      patient-reported associated symptoms. No significant difference was noted between
      PDL and IPL treatment. CONCLUSION: A series of nonpurpuragenic PDL and IPL
      treatments in ET rosacea was performed with similar efficacy and safety, and both
      modalities seem to be reasonable choices for the treatment of ET rosacea.

PMID- 19397668
TI  - Naturally occurring female hairline patterns.
AB  - BACKGROUND: Hair transplantation is gaining popularity in women. Although much
      has been written about hairline design in male patients, more information is
      needed about natural female hairlines. OBJECTIVE: To determine the frequency,
      dimensions, and location of structures that compose the female hairline. METHODS:
      Hairline characteristics were measured in 360 female volunteers at an informal
      hair salon setting. RESULTS: A widow's peak was present in 81%. The mean distance
      from the mid-eyebrow to the frontal midpoint was 5.5 cm. Lateral mounds were
      observed in 98%. The mean distance from the frontal midpoint to the apex of the
      lateral mounds was 3.74 cm on the right and 3.97 cm on the left. The mean
      distance from the apex of the lateral mounds to the apex of the temporal points
      was 3.78 cm on the right and 3.51 cm on the left. The shape of the temporal
      recessions was concave triangular or concave oval in 87% of the subjects.
      CONCLUSION: This study provides proposed guidelines for designing the hairline in
      women.

PMID- 19397669
TI  - Biologic dressings: current applications and limitations in dermatologic surgery.
AB  - BACKGROUND: Various biologic dressings have been developed in an effort to find
      the ideal skin substitute for use in acute and chronic wounds. There are many
      potential uses for such dressings, but no panaceas exist. Because millions of
      health care dollars are spent each year on wound care, and a great deal of
      patient morbidity occurs from these wounds, the search for new and better
      dressings is likely to continue. OBJECTIVE: To review the current evidence
      regarding the utility, outcomes, and adverse effects of the available biologic
      dressings, with a particular focus on use in acute surgical wounds and
      applicability to dermatologic surgery. MATERIALS AND METHODS: PubMed literature
      search and review of data on biologic dressings with particular attention to the
      past 2 decades. Emphasis was placed on peer-reviewed manuscripts and larger
      series. CONCLUSIONS: There is extensive literature regarding the use of biologic
      dressings in chronic wounds, such as venous leg ulcers and burns, but studies
      evaluating these dressings in acute surgical wounds and dermatologic surgery have
      been limited. There appear to be specific surgical settings in which such
      dressings may be of particular use, in addition to limitations of their use.
      Additional studies, particularly randomized and comparative trials, would be
      highly desirable.

PMID- 19397670
TI  - Familial cylindromatosis and brooke-spiegler syndrome: a review of current
      therapeutic approaches and the surgical challenges posed by two affected
      families.

PMID- 19397671
TI  - Fractional resurfacing for the treatment of atrophic facial acne scars in asian
      skin.
AB  - BACKGROUND: Atrophic facial acne scars is one of the most common problems in
      patients with inflammatory acne. Ablative laser resurfacing has unpleasant
      complications and a long recovery period. Nonablative therapies yield less
      improvement and satisfaction. The introduction of fractional photothermolysis
      (FP) is an alternative treatment for atrophic acne scars. OBJECTIVE: To evaluate
      the effectiveness and safety of a nonablative 1,550-nm erbium-doped fiber laser
      in the FP of atrophic facial acne scars in one treatment session. METHODS: Forty
      five patients (skin type III-IV, mean age 29) with atrophic facial acne scars
      were enrolled in the study. Each patient received one treatment of FP.
      Comparative photographs were taken using specific complexion analysis to identify
      and quantify depressed scars and texture. Physician evaluations and patient
      satisfaction were graded on a 4-point scale. Side effects were recorded at each
      follow-up visit. RESULTS: The improvement in atrophic scars and texture after a
      FP treatment were significant. Twenty-seven (60%) of the patients had good to
      excellent results after 1 month. CONCLUSION: The FP of atrophic facial acne scars
      resulted in significant improvement even in a single treatment, with good
      satisfaction and unremarkable side effects.

PMID- 19397672
TI  - Improvement of postfractional laser erythema with light-emitting diode
      photomodulation.
AB  - BACKGROUND: The most common side effects of fractional laser skin treatment are
      erythema and edema. Low-level light therapy and light-emitting diode (LED)
      devices have been used to stimulate fibroblast activity and hasten wound healing.
      OBJECTIVE: To determine whether LED treatment immediately after fractional laser
      skin resurfacing affects the severity and duration of postoperative eythema.
      MATERIALS AND METHODS: Twenty patients received treatment with a 590-nm
      wavelength LED array to randomly selected facial halves immediately after
      undergoing full-face fractional laser skin resurfacing with a 1,550-nm erbium
      doped fiber laser. Differences in erythema between LED-treated and untreated
      facial halves were recorded at 24, 48, and 96 hours post-treatment. RESULTS: The
      LED-treated facial halves were less erythematous in all 20 patients 24 hours
      postoperatively. The six patients who received the highest mean energy densities
      during fractional laser treatment continued to exhibit decreased erythema in the
      LED-treated areas at 48 hours. At 96 hours post-treatment, no discernible
      differences between facial halves were observed in any patient. CONCLUSIONS:
      Photomodulation with a 590-nm-wavelength LED array can decrease the intensity and
      duration of postfractional laser treatment erythema.

PMID- 19397673
TI  - Randomized double-blind clinical trial of subcutaneously injected deoxycholate
      versus a phosphatidylcholine-deoxycholate combination for the reduction of
      submental fat.
AB  - BACKGROUND: Subcutaneous injections consisting of the detergent, sodium
      deoxycholate, alone or in combination with the phospholipid, phosphatidylcholine,
      have been reported to reduce adipose tissue. The role of phosphatidylcholine
      remains unclear. OBJECTIVE: To evaluate the safety profile and efficacy of
      subcutaneously injected deoxycholate alone compared with a conventionally
      utilized mixture of phosphatidylcholine/deoxycholate in patients with undesirable
      accumulations of submental fat. METHODS: This was a single center, randomized,
      double-blind exploratory study. A total of 42 subjects were enrolled; 28 were
      injected into the submental fat with 1 mL of deoxycholate or
      phosphatidylcholine/deoxycholate, and 14 received 2 mL per treatment. Subjects
      received up to 5 treatments every four weeks, and completed a home diary and post
      treatment self-assessment. Clinicians blinded to treatment performed injections,
      physical examination, and photographic evaluation. RESULTS: Photographic
      assessment of 32 of the 42 enrolled patients revealed modest changes in submental
      profiles after a median of 5 deoxycholate or 4 phosphatidylcholine/deoxycholate
      treatments. Mean degree of improvement (0=none, 1=mild, 2=moderate,
      3=significant) was 0.8 (+/-0.9) for deoxycholate and 0.6 (+/-0.5) for
      phosphatidylcholine/deoxycholate, with a median improvement of 0.5 (range, 0-3)
      for both groups. The incidence of correct before:after photographic sequence
      assignments was similar. There were no notable differences on physical
      examination, incidence, duration, and severity of adverse events (most commonly
      edema, erythema, pain, and burning) or subject self-assessment of fat loss, skin
      tightening, chin profile, and overall performance between the treatments.
      CONCLUSION: Under the conditions employed, injections of deoxycholate or
      phosphatidylcholine/deoxycholate into the submental fat produced minimal
      aesthetic improvement overall. No apparent differences in efficacy or adverse
      events were observed with the inclusion of phosphatidylcholine. Enhanced neck
      profiles in several subjects demonstrate a proof of concept that warrants further
      study utilizing a validated, submental profile grading scale and methods to
      optimize dose and technique.

PMID- 19397674
TI  - Pyrosequencing analysis of endosymbiont population structure: co-occurrence of
      divergent symbiont lineages in a single vesicomyid host clam.
AB  - Bacteria-eukaryote endosymbioses are perhaps the most pervasive co-evolutionary
      associations in nature. Here, intracellular chemosynthetic symbionts of deep-sea
      clams (Vesicomyidae) were analysed by amplicon pyrosequencing to explore how
      symbiont transmission mode affects the genetic diversity of the within-host
      symbiont population. Vesicomyid symbionts (Gammaproteobacteria) are presumed to
      be obligately intracellular, to undergo nearly strict vertical transmission
      between host generations, and to be clonal within a host. However, recent data
      show that vesicomyid symbionts can be acquired laterally via horizontal transfer
      between hosts or uptake from the environment, potentially creating opportunities
      for multiple symbiont strains to occupy the same host. Here, genotype-specific
      PCR and direct sequencing of the bacterial internal transcribed spacer initially
      demonstrated the co-occurrence of two symbiont strains, symA and symB (93.5% nt
      identity), in 8 of 118 Vesicomya sp. clams from 3 of 7 hydrothermal vent sites on
      the Juan de Fuca Ridge. To confirm multiple strains within individual clams,
      amplicon pyrosequencing of two symbiont loci was used to obtain deep-coverage
      measurements (mean: approximately 1500x coverage per locus per clam) of symbiont
      population structure. Pyrosequencing confirmed symA-symB co-occurrence for two
      individuals, showing the presence of both genotypes in amplicon pools. However,
      in the majority of clams, the endosymbiont population was remarkably homogenous,
      with > 99.5% of sequences collapsing into a single symbiont genotype in each
      clam. These results support the hypothesis that a predominantly vertical
      transmission strategy leads to the fixation of a single symbiont strain in most
      hosts. However, mixed symbiont populations do occur in vesicomyids, potentially
      facilitating the exchange of genetic material between divergent symbiont
      lineages.

PMID- 19397675
TI  - Distribution and evolution of ferripyoverdine receptors in Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is a ubiquitous gram-negative bacterium, which is also
      able to cause severe opportunistic infections in humans. The colonization of the
      host is importantly affected by the production of the high-affinity iron (III)
      scavenging peptidic siderophore pyoverdine. The species P. aeruginosa can be
      divided into three subgroups ('siderovars'), each characterized by the production
      of a specific pyoverdine and receptor (FpvA). We used a multiplex PCR to
      determine the FpvA siderovar on 345 P. aeruginosa strains from environmental or
      clinical origin. We found about the same proportion of each type in clinical
      strains, while FpvA type I was slightly over-represented (49%) in environmental
      strains. Our multiplex PCR also detected the presence or absence of an additional
      receptor for type I pyoverdine (FpvB). The fpvB gene was in fact present in the
      vast majority of P. aeruginosa strains (93%), regardless of their siderovar or
      their origin. Finally, molecular analyses of fpvA and fpvB genes highlighted a
      complex evolutionary history, probably linked to the central role of iron
      acquisition in the ecology and virulence of P. aeruginosa.

PMID- 19397676
TI  - The role of pH in determining the species composition of the human colonic
      microbiota.
AB  - The pH of the colonic lumen varies with anatomical site and microbial
      fermentation of dietary residue. We have investigated the impact of mildly acidic
      pH, which occurs in the proximal colon, on the growth of different species of
      human colonic bacteria in pure culture and in the complete microbial community.
      Growth was determined for 33 representative human colonic bacteria at three
      initial pH values (approximately 5.5, 6.2 and 6.7) in anaerobic YCFA medium,
      which includes a mixture of short-chain fatty acids (SCFA) with 0.2% glucose as
      energy source. Representatives of all eight Bacteroides species tested grew
      poorly at pH 5.5, as did Escherichia coli, whereas 19 of the 23 gram-positive
      anaerobes tested gave growth rates at pH 5.5 that were at least 50% of those at
      pH 6.7. Growth inhibition of B. thetaiotaomicron at pH 5.5 was increased by the
      presence of the SCFA mix (33 mM acetate, 9 mM propionate and 1 mM each of iso
      valerate, valerate and iso-butyrate). Analysis of amplified 16S rRNA sequences
      demonstrated a major pH-driven shift within a human faecal bacterial community in
      a continuous flow fermentor. Bacteroides spp. accounted for 27% of 16S rRNA
      sequences detected at pH 5.5, but 86% of sequences at pH 6.7. Conversely,
      butyrate-producing gram-positive bacteria related to Eubacterium rectale
      represented 50% of all 16S rRNA sequences at pH 5.5, but were not detected at pH
      6.7. Inhibition of the growth of a major group of gram-negative bacteria at
      mildly acidic pH apparently creates niches that can be exploited by more low pH
      tolerant microorganisms.

PMID- 19397677
TI  - Survival and persistence of human and ruminant-specific faecal Bacteroidales in
      freshwater microcosms.
AB  - Amplification of host-specific markers from Bacteroidales faecal anaerobes can
      rapidly identify the source of faecal pollution. It is necessary to understand
      persistence and survival of these markers and marker cells, both to interpret
      quantitative source-tracking data, and to use such data to predict pathogen
      occurrence. We measured marker persistence and cell survival of two human (HF134,
      HF183) and two ruminant (CF128, CF193) faecal Bacteroidales markers, compared
      with Escherichia coli and enterococci. Freshwater microcosms were inoculated with
      fresh cattle or human faeces and incubated at 13 degrees C in natural light or
      darkness. Marker persistence was measured by polymerase chain reaction (PCR) and
      quantitative PCR. Survival of marker cells was measured by real-time quantitative
      PCR. There was no difference in persistence between the two human-specific
      Bacteroidales DNA markers in the light and dark microcosms. Cell survival
      profiles of the two human markers were also similar; both were significantly
      affected by light. Ruminant markers persisted and survived longer than human
      markers (14 versus 6 days respectively). CF193 decreased more rapidly than CF128,
      and light significantly affected CF128 but not CF193. These results support use
      of host-specific faecal Bacteroidales markers as indicators of recent faecal
      pollution, but suggest that caution is needed in interpreting quantitative
      results to indicate proportional contribution of different sources, as individual
      markers differ in their survival, persistence and response to environmental
      variables. The survival and persistence profiles for Bacteroidales markers are
      consistent with survival profiles for several faecal pathogens.

PMID- 19397678
TI  - Metagenomic analysis of stressed coral holobionts.
AB  - The coral holobiont is the community of metazoans, protists and microbes
      associated with scleractinian corals. Disruptions in these associations have been
      correlated with coral disease, but little is known about the series of events
      involved in the shift from mutualism to pathogenesis. To evaluate structural and
      functional changes in coral microbial communities, Porites compressa was exposed
      to four stressors: increased temperature, elevated nutrients, dissolved organic
      carbon loading and reduced pH. Microbial metagenomic samples were collected and
      pyrosequenced. Functional gene analysis demonstrated that stressors increased the
      abundance of microbial genes involved in virulence, stress resistance, sulfur and
      nitrogen metabolism, motility and chemotaxis, fatty acid and lipid utilization,
      and secondary metabolism. Relative changes in taxonomy also demonstrated that
      coral-associated microbiota (Archaea, Bacteria, protists) shifted from a healthy
      associated coral community (e.g. Cyanobacteria, Proteobacteria and the
      zooxanthellae Symbiodinium) to a community (e.g. Bacteriodetes, Fusobacteria and
      Fungi) of microbes often found on diseased corals. Additionally, low-abundance
      Vibrio spp. were found to significantly alter microbiome metabolism, suggesting
      that the contribution of a just a few members of a community can profoundly shift
      the health status of the coral holobiont.

PMID- 19397679
TI  - Microbial communities in iron-silica-rich microbial mats at deep-sea hydrothermal
      fields of the Southern Mariana Trough.
AB  - The abundance, diversity and composition of bacterial and archaeal communities in
      the microbial mats at deep-sea hydrothermal fields were investigated, using
      culture-independent 16S rRNA and functional gene analyses combined with
      mineralogical analysis. Microbial mats were collected at two hydrothermal areas
      on the ridge of the back-arc spreading centre in the Southern Mariana Trough.
      Scanning electron microscope and energy dispersive X-ray spectroscopic (SEM-EDS)
      analyses revealed that the mats were mainly composed of amorphous silica and
      contained numerous filamentous structures of iron hydroxides. Direct cell
      counting with SYBR Green I staining showed that the prokaryotic cell densities
      were more than 10(8) cells g(-1). Quantitative polymerase chain reaction (Q-PCR)
      analysis revealed that Bacteria are more abundant than Archaea in the microbial
      communities. Furthermore, zetaproteobacterial cells accounted for 6% and 22% of
      the prokaryotic cells in each mat estimated by Q-PCR with newly designed primers
      and TaqMan probe. Phylotypes related to iron-oxidizers,
      methanotrophs/methylotrophs, ammonia-oxidizers and sulfate-reducers were found in
      the 16S rRNA gene clone libraries constructed from each mat sample. A variety of
      unique archaeal 16S rRNA gene phylotypes, several pmoA, dsrAB and archaeal amoA
      gene phylotypes were also recovered from the microbial mats. Our results provide
      insights into the diversity and abundance of microbial communities within
      microbial mats in deep-sea hydrothermal fields.

PMID- 19397680
TI  - Identification of a calcium-controlled negative regulatory system affecting
      Vibrio cholerae biofilm formation.
AB  - Vibrio cholerae's capacity to cause outbreaks of cholera is linked to its
      survival and adaptability to changes in aquatic environments. One of the
      environmental conditions that can vary in V. cholerae's natural aquatic habitats
      is calcium (Ca(+2)). In this study, we investigated the response of V. cholerae
      to changes in extracellular Ca(2+) levels. Whole-genome expression profiling
      revealed that Ca(2+) decreased the expression of genes required for biofilm
      matrix production. Luria-Bertani (LB) medium supplemented with Ca(2+) (LBCa(2+))
      caused V. cholerae to form biofilms with decreased thickness and increased
      roughness, as compared with biofilms formed in LB. Furthermore, addition of
      Ca(2+) led to dissolution in biofilms. Transcription of two genes encoding a two
      component regulatory system pair, now termed calcium-regulated sensor (carS) and
      regulator (carR), was decreased in cells grown in LBCa(2+). Analysis of null and
      overexpression alleles of carS and carR revealed that expression of vps
      (Vibriopolysaccharide) genes and biofilm formation are negatively regulated by
      the CarRS two-component regulatory system. Through epistasis analysis we
      determined that CarR acts in parallel with HapR, the negative regulator of vps
      gene expression.

PMID- 19397681
TI  - Co-occurrence of denitrification and nitrogen fixation in a meromictic lake, Lake
      Cadagno (Switzerland).
AB  - The nitrogen cycling of Lake Cadagno was investigated by using a combination of
      biogeochemical and molecular ecological techniques. In the upper oxic freshwater
      zone inorganic nitrogen concentrations were low (up to approximately 3.4 microM
      nitrate at the base of the oxic zone), while in the lower anoxic zone there were
      high concentrations of ammonium (up to 40 microM). Between these zones, a narrow
      zone was characterized by no measurable inorganic nitrogen, but high microbial
      biomass (up to 4 x 10(7) cells ml(-1)). Incubation experiments with (15)N-nitrite
      revealed nitrogen loss occurring in the chemocline through denitrification
      (approximately 3 nM N h(-1)). At the same depth, incubations experiments with
      (15)N(2)- and (13)C(DIC)-labelled bicarbonate, indicated substantial N(2)
      fixation (31.7-42.1 pM h(-1)) and inorganic carbon assimilation (40-85 nM h(-1)).
      Catalysed reporter deposition fluorescence in situ hybridization (CARD-FISH) and
      sequencing of 16S rRNA genes showed that the microbial community at the
      chemocline was dominated by the phototrophic green sulfur bacterium Chlorobium
      clathratiforme. Phylogenetic analyses of the nifH genes expressed as mRNA
      revealed a high diversity of N(2) fixers, with the highest expression levels
      right at the chemocline. The majority of N(2) fixers were related to Chlorobium
      tepidum/C. phaeobacteroides. By using Halogen In Situ Hybridization-Secondary Ion
      Mass Spectroscopy (HISH-SIMS), we could for the first time directly link
      Chlorobium to N(2) fixation in the environment. Moreover, our results show that
      N(2) fixation could partly compensate for the N loss and that both processes
      occur at the same locale at the same time as suggested for the ancient Ocean.

PMID- 19397682
TI  - Carotenoids provide the major antioxidant defence in the globally significant N2
      fixing marine cyanobacterium Trichodesmium.
AB  - Photosynthetic oxygen-evolving microorganisms contend with continuous self
      production of molecular oxygen and reactive oxygen species. The deleterious
      effects of reactive oxygen species are exacerbated for cyanobacterial nitrogen
      fixers (diazotrophs) due to the innate sensitivity of nitrogenase to oxygen. This
      renders incompatible the processes of oxygen-evolving photosynthesis and N
      fixation. We examined total antioxidative potential of various diazotrophic and
      non-diazotrophic cyanobacteria. We focused on Trichodesmium spp., a bloom-forming
      marine diazotroph that contributes significantly to global nitrogen fixation.
      Among the species tested, Trichodesmium possessed the highest antioxidant
      activity. Moreover, while proteins constituted the dominant antioxidative
      component of all other cyanobacteria tested, Trichodesmium was unique in that
      small-molecule natural products provided the majority of antioxidant activity,
      while proteins constituted only 13% of total antioxidant activity. Bioassay
      guided fractionation followed by high-performance liquid chromatography profiling
      of antioxidant purified fractions identified the highly potent antioxidant all
      trans-beta-carotene, and small amounts of 9-cis-beta-carotene and retinyl
      palmitate. Search of the Trichodesmium genome identified protein sequences
      homologous to key enzymes in the beta-carotene to retinyl palmitate biosynthetic
      pathway, including 33-37% identity to lecithin retinol acyltransferase. The
      present study demonstrates the importance of carotenoids in Trichodesmium's
      arsenal of defensive compounds against oxidative damage and protection of
      nitrogenase from oxygen and its radicals.

PMID- 19397683
TI  - RNA silencing in the model mycorrhizal fungus Laccaria bicolor: gene knock-down
      of nitrate reductase results in inhibition of symbiosis with Populus.
AB  - Mycorrhizal symbioses are a rule in nature and may have been crucial in plant and
      fungal evolution. Ectomycorrhizas are mutualistic interactions between tree roots
      and soil fungi typical of temperate and boreal forests. The functional analysis
      of genes involved in developmental and metabolic processes, such as N nutrition,
      is important to understand the ontogeny of this mutualistic symbiosis. RNA
      silencing was accomplished in the model mycorrhizal fungus Laccaria bicolor by
      Agrobacterium-mediated gene transfer. Promoter-directed expression of double
      stranded RNA with a partial coding sequence of the Laccaria nitrate reductase
      gene resulted in fungal transgenic strains strongly affected in growth with
      nitrate as N source in a medium with high concentration of an utilizable C
      source. The phenotype correlated with a clear reduction of the target gene mRNA
      level and this effect was not caused by homologous recombination of the T-DNA in
      the nitrate reductase locus. Transformation with the hairpin sequence resulted in
      specific CpG methylation of both the silenced transgene and the nitrate reductase
      encoding gene. The methylation in the target gene was restricted to the silencing
      trigger sequence and did not represent the entire genomic DNA in the dikaryon
      suggesting that the epigenetic changes accompanying RNA silencing affected only
      the transformed nucleus. Mycorrhization experiments of Populus with strongly
      silenced fungal strains revealed a systematic inhibition of symbiosis under
      mycorrhization conditions (C starvation) and nitrate as N source compared with
      the wild type. This inhibition of mycorrhization was reversed by an organic N
      source only utilizable by the fungus. These observations would indicate that the
      plant may be capable of monitoring and detecting the nutritional status of a
      potential symbiont avoiding the establishment of an unsatisfactory interaction. A
      probable control mechanism conducted by the plant would inhibit symbiosis when
      the metabolic profile of the fungal partner is not proper and mutual benefit from
      the symbiotic structure cannot be assured. Our results are the first report
      showing that the alteration of expression of a fungal gene impairs
      mycorrhization. Moreover, this work is the first demonstration of RNA silencing
      in mycorrhizal fungi and clearly shows that gene knock-down is a powerful tool
      for further functional genomic studies in mycorrhizal research.

PMID- 19397684
TI  - Is the distribution of nitrogen-fixing cyanobacteria in the oceans related to
      temperature?
AB  - Approximately 50% of the global natural fixation of nitrogen occurs in the oceans
      supporting a considerable part of the new primary production. Virtually all
      nitrogen fixation in the ocean occurs in the tropics and subtropics where the
      surface water temperature is 25 degrees C or higher. It is attributed almost
      exclusively to cyanobacteria. This is remarkable firstly because diazotrophic
      cyanobacteria are found in other environments irrespective of temperature and
      secondly because primary production in temperate and cold oceans is generally
      limited by nitrogen. Cyanobacteria are oxygenic phototrophic organisms that
      evolved a variety of strategies protecting nitrogenase from oxygen inactivation.
      Free-living diazotrophic cyanobacteria in the ocean are of the non-heterocystous
      type, namely the filamentous Trichodesmium and the unicellular groups A-C. I will
      argue that warm water is a prerequisite for these diazotrophic organisms because
      of the low-oxygen solubility and high rates of respiration allowing the organism
      to maintain anoxic conditions in the nitrogen-fixing cell. Heterocystous
      cyanobacteria are abundant in freshwater and brackish environments in all
      climatic zones. The heterocyst cell envelope is a tuneable gas diffusion barrier
      that optimizes the influx of both oxygen and nitrogen, while maintaining anoxic
      conditions inside the cell. It is not known why heterocystous cyanobacteria are
      absent from the temperate and cold oceans and seas.

PMID- 19397685
TI  - Triggering of suicidal erythrocyte death by radiocontrast agents.
AB  - BACKGROUND: According to in vitro observations, gadolinium-containing magnetic
      resonance (MRT) contrast agents stimulate suicidal cell death or apoptosis.
      Similar to nucleated cells, erythrocytes may undergo suicidal death or eryptosis,
      characterized by cell shrinkage and cell membrane scrambling with
      phosphatidylserine (PS) exposure at the erythrocyte surface. Eryptosis is
      triggered by increased cytosolic Ca2+-activity. This study explored whether
      gadolinium-containing MRT contrast agents stimulate eryptosis. MATERIALS AND
      METHODS: Annexin V-binding reflecting PS exposure and forward scatter reflecting
      cell volume were determined in erythrocytes within freshly drawn blood from
      patients (8female symbol, 3male symbol, 29-72 years) prior to and 10 min after
      administration of gadoterate meglumine (0.1 mmol kg(-1) b.w. Dotarem; six
      patients) or gadobenate dimeglumine (0.05 mmol kg(-1) bw Multi Hance; five
      patients). In a separate series, eryptosis was determined prior to and following
      in vitro incubation of erythrocytes from 16 blood donors for 4 h with gadoterate
      meglumine (5 mM Dotarem) or gadobenate dimeglumine (5 mM Multi Hance). Finally,
      eryptosis and Fluo3 fluorescence reflecting cytosolic Ca2+ were determined in
      vitro following exposure to Gd3+. Data were analysed using paired t-test or anova
      with Tukey's test as post-test. RESULTS: The MRT contrast agents such as
      gadoterate meglumine (Dotarem) and gadobenate dimeglumine (Multi Hance)
      significantly increased the percentage of eryptotic cells. Moreover, in vitro
      exposure to gadoterate meglumine (5 mM), gadobenate dimeglumine (5 mM) or Gd3+
      (1.9 microM) stimulated eryptosis in vitro. The effect of Gd3+ was paralleled by
      increase in cytosolic Ca2+-activity. CONCLUSIONS: MRT contrast agents may
      stimulate suicidal erythrocyte death or eryptosis in vitro and in vivo.

PMID- 19397686
TI  - Mesangial medium with IgA1 from IgA nephropathy inhibits nephrin expression in
      mouse podocytes.
AB  - BACKGROUND: IgA nephropathy (IgAN) is characterized by mesangial deposition of
      polymeric IgA1, and podocyte injury plays an important role in glomerulosclerosis
      of the disease. Our previous study indicated that medium of mesangial cells co
      incubated with aggregated IgA1 (aIgA1), isolated from IgAN patients, down
      regulated nephrin expression. Yet the mechanism remains unclear. MATERIALS AND
      METHODS: Podocytes were incubated with a medium of mesangial cells co-incubated
      with aIgA1, which was isolated from IgAN patients, and enalaprilat (10(-5) M),
      valsartan (10(-5) M) and anti-mouse tumour necrosis factor-alpha antibody (50 ng
      mL(-1)) separately. Nephrin expression in podocytes was measured by real-time
      polymerase chain reaction and Western blot analysis. RESULTS: The level of
      angiotensinogen and angiotensin-converting enzyme mRNAs in podocytes, as well as
      angiotensin, was also increased by a medium of mesangial cells co-incubated with
      aIgA1 from IgAN patients (P<0.05). Enalaprilat or valsartan partly improved
      nephrin expression when compared with that by podocytes exposed to the mesangial
      medium (P<0.05), while the nephrin expression of podocytes with enalaprilat or
      valsartan was lower than that of podocytes exposed to medium of mesangial cells
      stimulated by aIgA1 from healthy control (P<0.05). However, anti-mouse tumour
      necrosis factor-alpha antibody did not show any improvement in nephrin
      expression. CONCLUSION: Our findings implicate that local renin angiotensin
      system activation in podocytes is partly involved in down-regulation of nephrin
      by mesangial medium in IgA nephropathy.

PMID- 19397687
TI  - Effect of polymerized-type I collagen in knee osteoarthritis. II. In vivo study.
AB  - BACKGROUND: Polymerized-Type I Collagen (Polymerized-Collagen) is an anti
      inflammatory and a tissue regenerator biodrug. The aim of the study was to
      evaluate the efficacy and safety of intra-articular injections of Polymerized
      Collagen in patients with knee osteoarthritis (OA). METHODS AND DESIGN: Patients
      (n=53) were treated with 12 intra-articular injections of 2 mL of Polymerized
      Collagen (n=27) or 2 mL of placebo (n=26) during 6 months. Follow up period was 6
      months. The primary endpoints included Western Ontario and McMaster University
      Osteoarthritis Index, Lequesne index, and pain intensity on a visual analogue
      scale (VAS). Secondary outcomes were patient global score, investigator global
      score and drug evaluation. Clinical improvement was determined if the decrease in
      pain exceeds 20 mm on a VAS and patients achieved at least 20% of improvement
      from baseline. Urinary levels of C-terminal crosslinking telopeptide of collagen
      type II (CTXII) and serum high-sensitivity C-reactive protein (hsCRP) were
      determined by enzyme immunoassays. Statistical analysis was performed by
      intention to treat. RESULTS: Polymerized-Collagen was safe and well tolerated.
      Patients had a statistically significant improvement (P<0.05) from baseline vs.
      Polymerized-Collagen and vs. placebo at 6 months in: Lequesne Index (13.1+/-0.5
      vs. 7.1+/-0.7 vs. 9.6+/-0.8; P=0.027), WOMAC (9.0+/-0.5 vs. 4.0+/-0.6 vs. 5.80+/
      0.8; P=0.032), patient VAS (60.0+/-2.6 vs. 20.6+/-2.4 vs. 36.1+/-4.5; P=0.003),
      physician VAS (49.8+/-1.9 vs. 16.8+/-2.9 vs. 29.8+/-2.9; P=0.002), patient global
      score (1.08+/-0.1 vs. 2.7+/-0.1 vs. 1.9+/-0.2; P=0.028) and analgesic usage
      (30.1+/-9.4 vs. 11.0+/-3.4 vs. 17.9+/-4.9; P=0.001). This improvement was
      persistent during the follow up. A threefold increase in CTXII was determined in
      placebo group. No differences were found on hs CRP and incidence of adverse
      events between groups. CONCLUSION: Polymerized-Collagen is safe and effective in
      the treatment of knee OA.

PMID- 19397688
TI  - Physicochemical properties of ferumoxytol, a new intravenous iron preparation.
AB  - BACKGROUND: Intravenous iron is a critical component of anaemia management.
      However, currently available preparations have been associated with the release
      of free iron, a promoter of bacterial growth and oxidative stress. MATERIALS AND
      METHODS: We determined the molecular weight, dialysability and capacity for free
      iron release of ferumoxytol, a semi-synthetic carbohydrate-coated
      superparamagnetic iron oxide nanoparticle. Ferumoxytol was compared with three
      intravenous iron preparations in clinical use: iron dextran (low molecular
      weight), sodium ferric gluconate and iron sucrose. Intravenous iron preparations
      were also incubated in rat, and pooled human sera (at concentrations of 600
      microM and 42 microg mL(-1) respectively) from healthy subjects. RESULTS: The
      molecular weight of ferumoxytol was 731 kDa. The relative order of molecular
      weight was as follows: ferumoxytol > iron dextran > iron sucrose > sodium ferric
      gluconate. The least ultrafilterable iron was observed with ferumoxytol and the
      most with ferric gluconate. The least dialysable free iron was observed with
      ferumoxytol and the most with ferric gluconate. Incubation of intravenous iron
      preparations in rat or pooled human sera demonstrated minimal free iron release
      with ferumoxytol. The order of catalytic iron release as detected by the
      bleomycin detectable iron assay was as follows: ferumoxytol < iron dextran < iron
      sucrose < ferric gluconate. A similar trend was observed for the in vivo serum
      concentration of free iron in rats. CONCLUSIONS: In vitro observations from these
      experiments suggest that ferumoxytol has a favourable profile in terms of
      tendency to release free iron, in comparison with currently available intravenous
      iron preparations.

PMID- 19397689
TI  - Serine protease activity of Per a 10 augments allergen-induced airway
      inflammation in a mouse model.
AB  - BACKGROUND: We recently reported an immunodominant serine protease allergen (Per
      a 10) from Periplaneta americana. This study investigates the role of its
      proteolytic activity in driving the immune responses towards self and other
      allergens. MATERIALS AND METHODS: Groups of Balb/c mice were sensitized
      intraperitoneally and subcutaneously with proteolytically active Per a 10 or
      inactivated Per a 10 (using aminoethyl benzenesulfonyl fluoride hydrochloride) or
      whole body P. americana extract and subsequently challenged intranasally with the
      respective antigens. Mice were also sensitized and challenged with ovalbumin
      (OVA) alone or co-administered with active or inactive Per a 10. The immune
      inflammatory responses were measured by airway hyperresponsiveness (AHR) and
      cellular infiltration of lungs i.e. eosinophil counts, eosinophil peroxidase
      (EPO) activity, myeloperoxidase activity (MPO), lung histopathology, serum levels
      of specific-antibodies and levels of Th1/Th2 interleukins in bronchoalveolar
      lavage fluid (BALF) and in spleen cells culture supernatant. RESULTS: Mice
      challenged with active Per a 10/P. americana extract showed a significant airway
      inflammation demonstrated by enhanced AHR and increased cellular infiltration of
      lungs as evidenced by high eosinophil counts, EPO activity, IL-4 and IL-5 in
      BALF. Active Per a 10 also induced a significant proliferation of spleen cells,
      increased secretion of IL-4 and IL-5 in the spleen cells culture supernatant and
      systemic production of specific-IgE and IgG1. However, exposure with inactive Per
      a 10 elicited a low cellular infiltration and systemic antibody production.
      Exposure to OVA with active Per a 10 demonstrated a significantly high cellular
      infiltration and production of OVA-specific IgE and IgG1, than exposure to OVA
      alone or with inactive Per a 10. CONCLUSIONS: Proteolytic activity of Per a 10
      plays an important role in driving the allergic immune response by providing an
      adjuvant effect, towards self and other potential allergens present in the same
      microenvironment.

PMID- 19397690
TI  - Irradiated cultured apoptotic peripheral blood mononuclear cells regenerate
      infarcted myocardium.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is followed by post AMI cardiac
      remodelling, often leading to congestive heart failure. Homing of c-kit+
      endothelial progenitor cells (EPC) has been thought to be the optimal source for
      regenerating infarcted myocardium. METHODS: Immune function of viable peripheral
      blood mononuclear cells (PBMC) was evaluated after co-culture with irradiated
      apoptotic PBMC (IA-PBMC) in vitro. Viable PBMC, IA-PBMC and culture supernatants
      (SN) thereof were obtained after 24 h. Reverse transcription polymerase chain
      reaction and enzyme-linked immunosorbent assay were utilized to quantify
      interleukin-8 (IL-8), vascular endothelial growth factor, matrix
      metalloproteinase-9 (MMP9) in PBMC, SN and SN exposed fibroblasts. Cell
      suspensions of viable- and IA-PBMC were infused in an experimental rat AMI model.
      Immunohistological analysis was performed to detect inflammatory and pro
      angiogenic cells within 72 h post-infarction. Functional data and determination
      of infarction size were quantified by echocardiography and Elastica van Gieson
      staining. RESULTS: The IA-PBMC attenuated immune reactivity and resulted in
      secretion of pro-angiogenic IL-8 and MMP9 in vitro. Fibroblasts exposed to viable
      and IA-PBMC derived SN caused RNA increment of IL-8 and MMP9. AMI rats that were
      infused with IA-PBMC cell suspension evidenced enhanced homing of endothelial
      progenitor cells within 72 h as compared to control (medium alone, viable-PBMC).
      Echocardiography showed a significant reduction in infarction size and
      improvement in post AMI remodelling as evidenced by an attenuated loss of
      ejection fraction. CONCLUSION: These data indicate that infusion of IA-PBMC cell
      suspension in experimental AMI circumvented inflammation, caused preferential
      homing of regenerative EPC and replaced infarcted myocardium.

PMID- 19397691
TI  - Keratin 18 provides resistance to Fas-mediated liver failure in mice.
AB  - BACKGROUND: Keratins are intermediate filament proteins of epithelial cells with
      pivotal functions for cell integrity. They comprise keratins 18 [K18] and 8 [K8]
      in hepatocytes. Keratins are of major importance for an intact cellular
      microarchitecture and have protective functions in human liver diseases. In mice,
      K8 has been demonstrated to protect against Fas-antibody-induced liver failure by
      direct interaction with apoptotic regulators, while the role of K18 remains
      unresolved. MATERIALS AND METHODS: We analysed effects of K18 deficiency on Fas
      induced liver failure in mice. We determined survival and analysed induction of
      apoptosis after injection of the agonistic Fas antibody Jo2 into K18(-/-) and
      wild-type control mice by TUNEL assay and fluorometrically analysed caspase-3, -8
      and -9 activities 1, 2 and 3 h after Jo2 injection. RESULTS: In K18(-/-) mice,
      survival of Fas-antibody treated mice was significantly shorter than that of wild
      type controls (P = 0.02). However, shortened survival of K18(-/-) mice was caused
      by increased hepatic damage but was not correlated to enhanced induction of
      apoptotic pathways, as neither numbers of TUNEL positive apoptotic cells nor
      activities of caspases-3, -8 and -9 differed between K18(-/-) and K18(+/+) mice
      at any point of time. CONCLUSION: K18(-/-) mice are significantly more
      susceptible to Fas-antibody-induced liver failure. The cytoprotective effect of
      K18 is not explained by a differential activation of caspases-3, -8 and -9,
      suggesting that K18 does not directly interfere with apoptotic regulators.
      Importantly, however, K18 exerts significant protective functions by other
      mechanisms.

PMID- 19397692
TI  - Low-grade inflammation can partly explain the association between the metabolic
      syndrome and either coronary artery disease or severity of peripheral arterial
      disease: the CODAM study.
AB  - BACKGROUND: Low-grade inflammation has been hypothesized to underlie the coronary
      artery disease (CAD) risk associated with the metabolic syndrome, but the
      evidence is not conclusive. For peripheral arterial disease (PAD; as measured by
      the ankle-arm index), this association has not been studied before. The aim was
      to study whether the association between the metabolic syndrome and CAD or the
      severity of PAD can be explained by low-grade inflammation. METHODS: The Cohort
      study Diabetes and Atherosclerosis Maastricht population includes 574 subjects,
      with an increased risk of type 2 diabetes, of whom 560 were included in the
      analyses (343 males; age: 59.5 +/- 7.0 years). The inflammation markers that were
      measured were C-reactive protein, interleukin 6, soluble vascular cell adhesion
      molecule-1, soluble intercellular adhesion molecule-1 and serum amyloid A. All
      analyses were adjusted for age, sex and smoking. RESULTS: Logistic regression
      showed that the metabolic syndrome was significantly associated with CAD [odds
      ratio (OR) = 1.86, 95% CI: 1.21; 2.84, P = 0.004]. Further adjustment for
      inflammatory status, as captured in a combination of the inflammation markers
      (using an averaged Z-score), resulted in significant associations of both the
      metabolic syndrome and inflammatory status with CAD [OR(metabolic syndrome) (95%
      CI) = 1.58 (1.01; 2.46), P = 0.044; OR(inflammation) (95% CI) = 1.59 (1.14;
      2.21), P = 0.007]. Linear regression analysis showed similar results for the
      ankle-arm index. CONCLUSIONS: The association between the metabolic syndrome, on
      the one hand, and prevalence of CAD or the severity of PAD, on the other, can be
      partly but not completely, 26% and 29% respectively, explained by low-grade
      inflammation.

PMID- 19397693
TI  - Fluvastatin/fenofibrate vs. simvastatin/ezetimibe in patients with metabolic
      syndrome: different effects on LDL-profiles.
AB  - BACKGROUND: Patients with metabolic syndrome (MS) and type 2 diabetes (T2DM) show
      increased risk for coronary artery disease. Lipoprotein metabolism is
      characterized by elevated triglycerides (TG), low high-density lipoprotein
      cholesterol (HDL-C) and predominance of atherogenic small, dense low-density
      lipoprotein (sdLDL), while low-density lipoprotein (LDL) cholesterol is only
      slightly elevated. METHODS: Multicentre, randomized, open-label cross-over study
      investigating the effect of combination of fluvastatin/fenofibrate (80/200 mg)
      (F&F) on LDL-subfractions compared with combination of simvastatin/ezetimibe
      (20/10 mg) (S&E) in patients with MS/T2DM. RESULTS: Seventy-five patients were
      randomized, 69 completed the study and LDL-subfractions of 56 patients were
      analysed. Thirty-eight out of 56 patients (68%) showed a profile dominated by
      sdLDL. In these, TG and total cholesterol (TC) were elevated compared with non
      sdLDL patients. In all patients, reduction of TC and LDL cholesterol (LDL-C) by
      S&E was stronger than by F&F. The increase of HDL-C was stronger with S&E in the
      non-sdLDL group, whereas in the sdLDL group, there was no difference between
      treatments. In non-sdLDL patients, there was no effect on TG or LDL-radius.
      However, in the sdLDL group, F&F was more effective in reducing TG and increased
      LDL radius, whereas S&E reduced LDL radius even further. CONCLUSIONS: S&E is more
      efficient in reducing TC and LDL-C. This is also true for HDL-C increase in non
      sdLDL patients. However, in patients with sdLDL, F&F was more efficient in
      reducing TG and increasing LDL radius.

PMID- 19397694
TI  - Development of troponin autoantibodies in experimental coxsackievirus B3
      myocarditis.
AB  - BACKGROUND: Autoantibodies against various endogenous proteins are found in
      myocarditis. Troponin autoantibodies are detected in patients with chronic
      dilated cardiomyopathy, but their presence in myocarditis remains unknown. We set
      out to study the presence of troponin autoantibodies in experimental viral
      myocarditis. MATERIALS AND METHODS: BALB/c mice infected with coxsackievirus B3
      Nancy strain were followed-up at days 1-7 and 2, 4, 8 and 12 weeks after
      infection. Levels of circulating cardiac troponin I and circulating troponin
      autoantibodies were measured. Transthoracic echocardiography was performed.
      Myocarditis was histopathologically graded and cardiomyocyte apoptosis was
      quantified (TUNEL). RESULTS: Histopathologically relatively mild acute
      myocarditis followed by persistent cardiomyocyte damage was observed. Rate of
      cardiomyocyte apoptosis was the highest on day 5 (0.16 +/- 0.01% vs. 0.03 +/-
      0.01% in controls, P < 0.001). Circulating troponin I levels were increased to
      day 5 (45.2 +/- 6.5 ng mL(-1), P < 0.005 vs. controls). Troponin autoantibodies
      were detected from 2 weeks after infection (20% of animals had autoantibodies at
      2 weeks, 60% at 4 and 8 weeks and 20% at 12 weeks, P < 0.05 vs. controls).
      Fractional shortening remained decreased after acute myocarditis (0.36 +/- 0.02
      at 4 weeks, 0.30 +/- 0.02 at 8 and 12 weeks vs. 0.41 +/- 0.01 before infection, P
      < 0.01) parallel to development of troponin autoantibodies. CONCLUSION: Troponin
      autoantibodies are formed in experimental virus induced myocarditis following
      troponin I release and cardiomyocyte apoptosis. The definite role of these
      autoantibodies remains to be further characterized.

PMID- 19397695
TI  - A guide to hair follicle analysis by transmission electron microscopy: technique
      and practice.
AB  - Hair follicles contain several tissues and cell types that differentiate down
      distinct pathways to provide for growth, keratinization and the maintenance of
      the hair shaft. Electron microscopy is useful for examining the morphological
      characteristics of developing hair follicles, including special types of
      keratinization, the timing of keratinization, programmed cell death, cell
      adhesion and separation, cell movement and changes in organelles. Hair follicles
      are one of the more challenging targets for electron microscopic analysis, and
      the use of neonatal animals combined with careful treatment of the samples can
      yield informative photomicrographs. Detailed protocols and examples of a number
      of techniques are presented here.

PMID- 19397696
TI  - Keratinocytes: a source of the transmitter L-glutamate in the epidermis.
AB  - Various glutamate receptors have been described in both keratinocytes and
      melanocytes. L-Glutamate is the physiological agonist of the glutamate receptor
      family. The source of this transmitter had not yet been identified. In normal
      human epidermal keratinocytes (NHEK) and HaCaT-keratinocytes, cell supernatants
      were sampled in various stages of cell density and the l-glutamate content
      photometrically determined. The following examination time-points were defined:
      non-confluent (ca. 33%), subconfluent (ca. 70%) and confluent (90-100%). The L
      glutamate concentration originally in the culture medium was 14.7 mg/l (0.1
      mm/l). The L-glutamate concentration in the cell supernatant increased in NHEK
      with increasing cell density: non-confluent 39.9 + or - 4 mg/l, subconfluent 60.6
      + or - 15.8 mg/l, confluent 100.7 + or - 33.2 mg/l. A linear increase of L
      glutamate concentration was also found for HaCaT cells. The investigations show
      that keratinocytes are capable of producing and releasing L-glutamate. Thus they
      are a source of L-glutamate which acts as a transmitter on epidermal glutamate
      receptors.

PMID- 19397697
TI  - Calcium pantothenate modulates gene expression in proliferating human dermal
      fibroblasts.
AB  - Topical application of pantothenate is widely used in clinical practice for wound
      healing. Previous studies identified a positive effect of pantothenate on
      migration and proliferation of cultured fibroblasts. However, these studies were
      mainly descriptive with no molecular data supporting a possible model of its
      action. In this study, we first established conditions for an in vitro model of
      pantothenate wound healing and then analysed the molecular effects of
      pantothenate. To test the functional effect of pantothenate on dermal
      fibroblasts, cells were cultured and in vitro proliferation tests were performed
      using a standardized scratch test procedure. For all three donors analysed, a
      strong stimulatory effect of pantothenate at a concentration of 20 microg/ml on
      the proliferation of cultivated dermal fibroblasts was observed. To study the
      molecular mechanisms resulting in the proliferative effect of pantothenate, gene
      expression was analysed in dermal fibroblasts cultivated with 20 microg/ml of
      pantothenate compared with untreated cells using the GeneChip Human Exon 1.0 ST
      Array. A number of significantly regulated genes were identified including genes
      coding for interleukin (IL)-6, IL-8, Id1, HMOX-1, HspB7, CYP1B1 and MARCH-II.
      Regulation of these genes was subsequently verified by quantitative real-time
      polymerase chain reaction analysis. Induction of HMOX-1 expression by pantothenol
      and pantothenic acid in dermal cells was confirmed on the protein level using
      immunoblots. Functional studies revealed the enhanced suppression of free radical
      formation in skin fibroblasts cultured with panthenol. In conclusion, these
      studies provided new insight in the molecular mechanisms linked to the
      stimulatory effect of pantothenate and panthenol on the proliferation of dermal
      fibroblasts.

PMID- 19397698
TI  - Human papillomavirus 16 E6/E7-immortalized human gingival keratinocytes with
      epithelial mesenchymal transition acquire increased expression of cIAP-1, Bclx
      and p27(Kip1).
AB  - Epithelial mesenchymal transition (EMT) has been implicated in neoplastic
      invasion and metastasis. We have previously generated six cell lines from human
      gingival mucosal keratinocytes immortalized by E6/E7 of human papillomavirus type
      16. Ldk and NuB1 lines represented EMT phenotype and other four lines represented
      cobblestone non-EMT phenotype. These cell lines were utilized as model cells to
      determine whether inhibitors of apoptosis proteins and cell-cycle regulators were
      molecular players during EMT. EMT cells exhibited increased expression of
      vimentin, vascular endothelial growth factor (VEGF) receptor1 and the ability to
      form tubules on Matrigel as well as to grow anchorage independently. We found
      that EMT cells expressed significantly elevated levels of cIAP-1, Bclx and
      p27(kip) higher than non-EMT cells. These proteins could therefore be used as
      intrinsic indicators of EMT of human gingival keratinocytes.

PMID- 19397699
TI  - Migration and penetration of a fluorescent textile dye into the skin--in vivo
      versus in vitro methods.
AB  - The amount of textile dye migration from the textile and penetration into the
      skin is relevant when assessing the risk of textile dyes. In this paper, in vivo
      methods were developed using a harmless textile dye with a strong fluorescence
      and were then compared with in vitro methods. For the in vivo method, the textile
      was applied to the lower back of six volunteers wearing the textile 12 h and to
      the lower back of 12 volunteers during 30 min active sport. The maximum skin
      absorption of 55 +/- 17 ng/cm(2) was obtained in the group engaged in sports. The
      in vitro methods, which involved the application of the textile to the pig ear
      skin, was shown to yield similar results to the 12 h in vivo group (31.2 +/- 9.6
      ng/cm(2) vs 27 +/- 14 ng/cm(2)). The migration of the textiles into artificial
      sweat resulted in approximately 20 microg/cm(2). The disadvantage of such textile
      extract applications on pig ear skin is discussed. It could be demonstrated that
      the absorption of the dye is strongly correlated to the amount of sweat, whereas
      the contact time was less important.

PMID- 19397700
TI  - Angiotensin II activates connective tissue growth factor and induces
      extracellular matrix changes involving Smad/activation and p38 mitogen-activated
      protein kinase signalling pathways in human dermal fibroblasts.
AB  - Angiotensin II (Ang II) stimulation has been shown to regulate proliferation of
      skin fibroblasts and the production of extracellular matrix, which are very
      important processes in skin wound healing and fibrosis; however, there is little
      knowledge about the mechanisms involved in this process. We investigated the
      molecular aspects of this system with regards to Ang II in human dermal
      fibroblasts (HDF) and its potential role in fibrosis. Fibroblasts derived from
      human skin were subjected to examine differential relative gene and protein
      expression after transfection with specific reporter expression vectors and Ang
      II in vitro. In growth-arrested HDFs, Ang II treatment for 20 min caused acute
      activation of Smad2 phosphorylation, Smad overexpression and Smad-dependent gene
      transcription. The angiotensin type 1 (AT1) antagonist losartan diminished Ang II
      induced Smad activation. The blockade of endogenous transforming growth factor
      beta1 did modify the activation of Smad caused by Ang II. The p38 mitogen
      activated protein kinase (MAPK) inhibitor SB203580 diminished Ang II-induced
      Smad2 phosphorylation. Transient transfection with Smad7, which interferes with
      receptor-mediated activation of Smad2, diminished Ang II-induced connective
      tissue growth factor promoter activation, gene and protein expression and
      fibronectin, type I procollagen and type III procollagen overexpression, showing
      that Smad activation is involved in Ang II-induced dermal fibrosis. Our results
      show that Ang II activation of Smad2 occurs via the AT1 receptor, but not the AT2
      receptor. Activation of Smad2 required p38 MAPK but not p42/p44 MAPK or the
      epidermal growth factor receptor.

PMID- 19397703
TI  - Study on the interaction between 3 flavonoid compounds and alpha-amylase by
      fluorescence spectroscopy and enzymatic kinetics.
AB  - The interaction between alpha-amylase and 3 flavonoid compounds from tartary
      buckwheat bran, namely, quercetin (Que), its monoglycoside isoquercetin (Iso),
      and its diglycoside rutinb (Rut), has been studied by fluorescence spectroscopy
      and enzymatic kinetics. The results indicate that Que, Iso, and Rut could bind
      with alpha-amylase to form a new complex, which exhibits an obvious fluorescence
      quenching. We deduce that such a quenching is a static quenching via nonradiation
      energy transfer. Results from plots and calculations show that the sequence of
      binding constants (KA) is Iso > Que > Rut. Calculation on thermodynamic
      parameters reveals that the main driving force of above-mentioned interaction is
      hydrophobic. Enzyme activity measurements show that all of the 3 flavonoid
      compounds are effective inhibitors toward alpha-amylase, and the inhibitory mode
      belongs to a competitive type. The sequence of affinity (1/Ki) is in accordance
      with the results of binding constants (KA) from fluorescence experiments.

PMID- 19397704
TI  - Aroma evaluation of transgenic, thaumatin II-producing cucumber fruits.
AB  - Fruits of transgenic cucumber lines expressing preprothaumatin II gene were
      evaluated concerning their aroma. Four homozygous lines, that is, 210 06, 212 01,
      224 09, and 225 03 with different levels of transgene expression were selected.
      Recipient line cv. Borszczagowski, which was formed by inbred line of Cucumis
      sativus L., was used as a control. The experiment was carried out in a greenhouse
      and an outdoor experimental plot. The aroma of cucumber fruits was evaluated by
      GC/MS, as well as GC/MS/TOF in the distillates and by SPME. Irrespective of the
      isolation/separation technique used, the differences between aroma compounds in
      transgenic cucumbers and the control were quantitative, and not qualitative.
      Modified samples showed higher concentrations of volatiles, particularly of the
      main cucumber fruits odorant (E, Z)-2,6 nonadienal. Transgenic expression of the
      thaumatin II gene resulted not only in a sweeter taste of fruits in comparison
      with the control, but also higher aroma acceptability. This was shown by sensory
      profile analysis. Also electronic nose measurements differentiated between
      transgenic lines and the control.

PMID- 19397705
TI  - Effects of phosphates and salt in ground raw and cooked farmed cod (Gadus morhua)
      muscle studied by the water holding capacity (WHC), and supported by P-NMR
      measurements.
AB  - A model system consisting of ground farmed cod muscle (80%, w/w) and added brine
      (20%, w/w) with different content and combinations of salt (0% and 3% in brine)
      and phosphorus compounds (mono-, di-, tri- and hexametaphosphates; 0% and 3% in
      brine) was used to simulate industrial brining of muscle foods. Individual
      phosphorus component concentrations and breakdown as function of time (0, 23 h)
      were analyzed using (31)P-NMR spectroscopy. The effects of salt and phosphate on
      water holding capacity (WHC) were measured at similar sampling times, and
      interrelations between phosphorous components determined by NMR and WHC were
      established. Addition of salt led to a significant increase (+18%) in WHC, and
      the combined effect of salt and phosphates was even more pronounced (+29%). The
      positive effect of triphosphate and salt on WHC was also seen after cooking (+36%
      in raw and +41% in cooked cod muscle, relative to control), although NMR analysis
      showed a rapid breakdown of di- and triphosphates.

PMID- 19397706
TI  - Effect of actinidin on the protein solubility, water holding capacity, texture,
      electrophoretic pattern of beef, and on the quality attributes of a sausage
      product.
AB  - The objective of this study was to study the effect of actinidin, a sulfhydryl
      protease from kiwi fruit, on the protein solubility (nitrogen solubility index
      [NSI]), water holding capacity (WHC), texture, and SDS-PAGE pattern of beef and
      to evaluate the effect of pretreatment of beef with actinidin on the quality
      attributes of a sausage product. Actinidin was partially purified by
      precipitation with ammonium sulfate, followed by DEAE-Sephadex column
      chromatography. Actinidin significantly (P < 0.05) increased NSI and WHC of beef;
      the highest NSI and WHC (approximately 20% and 8% increase, respectively) was
      observed when beef was incubated with 0.9 unit enzyme/g beef. Texture analysis
      indicated increased tenderization (10% decrease in shear force) when slices of
      cattle beef were treated with actinidin at 37 degrees C for 2 h. SDS-PAGE results
      indicated appearance of several low molecular weight bands (<10 kDa) after
      treating beef with different levels of actinidin for 30 or 60 min. Slight changes
      in protein band in the range of 100 to 120 kDa and 13 to 25 kDa were also
      observed. Use of actinidin-tenderized beef significantly improved emulsion
      stability, texture, and organoleptic properties of the sausage product.

PMID- 19397707
TI  - Determination of anthocyanins, total phenolic content, and antioxidant activity
      in Andes Berry (Rubus glaucus Benth).
AB  - Anthocyanins, total phenolic content, ascorbic acid content, and the antioxidant
      activity were determined in extracts of Andes berry fruit (Rubus glaucus Benth).
      Anthocyanis (ACNs) were isolated and characterized by means of high-performance
      liquid chromatography (HPLC) with photodiode array detection and electro spray
      ionization/mass spectrometry (PDA-ESI/MS/MS) analysis. The anthocyanin (ACN)
      content was 45 mg/100 g FW. The isolated anthocyanins were characterized as
      cyanidin 3-sambubioside, cyanidin 3-glucoside, cyanidin 3-xylorutinoside,
      cyanidin 3-rutinoside, pelargonidin 3-glucoside, and pelargonidin 3-rutinoside.
      The ascorbic acid content was 10.1 mg/100 g FW. The total phenolic content as
      determined by the Folin-Ciocalteau method was 294 mg GAE/100 g FW while the
      antioxidant activity as measured by ABTS(.) (+) radical scavenging capacity and
      ferric reducing antioxidant power (FRAP) was 2.01 and 4.50 mmol TE/100 g FW or
      8.22 mmoles ferric iron reduced/100 g FW, respectively. The high phenolic content
      and antioxidant capacity of Andes berry suggest that this fruit could be a rich
      source of natural pigments, nutraceuticals, and natural antioxidants.

PMID- 19397708
TI  - Electrospun zein fibers as carriers to stabilize (-)-epigallocatechin gallate.
AB  - In this study, a method was developed for continuous electrospinning of ultrafine
      corn zein protein fibers with diameters ranging from 150 to 600 nm. Fiber-forming
      solutions with various zein concentrations (10% to 30%, w/w) and aqueous ethanol
      concentrations (60% to 90%, w/w) were electrospun at 15 and 20 kV. Scanning
      electron microscopy results showed that the morphology of zein fibers was
      affected by aqueous ethanol concentration, zein concentration, and the applied
      voltage. The optimal condition for forming bead-less fibers was found to be 20%
      protein, 70% alcohol, and 15 kV. The zein fibers resisted solubilization in
      water, although swelling and plasticization were apparent after the water
      treatment. The efficacy of zein fibers was tested for stabilization of a green
      tea polyphenol, (-)-epigallocatechin gallate (EGCG), by incorporating the EGCG in
      zein fiber-forming solutions. Freshly spun fibers were less effective at
      immobilizing the EGCG upon immersion in water (82% recovery) as compared to
      fibers that were aged at 0% relative humidity for at least 1 d (>98% recovery)
      before water immersion. Fourier transform infrared spectroscopy studies
      demonstrated that hydrogen bonding, hydrophobic interactions, and physical
      encapsulation are the major contributors to the stabilization of EGCG in zein
      fibers in water.

PMID- 19397709
TI  - Production and characterization of monoclonal antibodies specific to pangasius
      catfish, basa, and tra.
AB  - Four IgG (subclass IgG1) class monoclonal antibodies (MAbs) strongly reactive to
      Asian farm-raised Pangasius catfish, tra (Pangasius hypophthalmus) and basa
      (Pangasius bocourti), have been developed. These MAbs were raised by immunizing
      an animal with thermal-stable crude sarcoplasmic protein extract of cooked tra.
      The MAbs were selected by screening hybridoma clones against more than 70 common
      fish and meat protein extracts. Two MAbs, T7E10 and T1G11, were found to be
      specific to the Asian Pangasius catfish, tra, and basa, with no cross-reactions
      with any of the common fish and meat species or with the food additive proteins
      (bovine serum albumin, soy proteins, milk proteins, egg proteins, and gelatin)
      tested. MAb T7E10 recognized 2 antigenic proteins (molecular weight approximately
      36 and 75 kDa) in raw and cooked tra and basa extracts, while T1G11 bound to
      several proteins (molecular weight between 13 and 18 kDa) in tra and basa
      extracts. Two other MAbs, F7B8 and F1G11, recognized a common protein (36 KDa)
      and cross-reacted with all the fish extracts tested and with several mammalian
      species. These MAbs can be employed individually or in combination in various
      formats of immunoassays for rapid identification of Pangasius catfish, either raw
      or cooked. They can also be used to study the biological, biochemical, and
      physiological aspects of thermal-stable antigenic proteins. This is the first
      study identifying these thermal-stable antigenic proteins present in Pangasius
      catfish as species-specific biomarkers.

PMID- 19397710
TI  - Stabilizing oils from smoked pink salmon (Oncorhynchus gorbuscha).
AB  - Smoking of meats and fish is one of the earliest preservation technologies
      developed by humans. In this study, the smoking process was evaluated as a method
      for reducing oxidation of pink salmon (Oncorhynchus gorbuscha) oils and also
      maintaining the quality of oil in aged fish prior to oil extraction. Salmon heads
      that were subjected to high temperatures (95 degrees C) during smoking
      unexpectedly produced oils with fewer products of oxidation than their
      unprocessed counterparts, as measured by peroxide value (PV), thiobarbituric acid
      reactive substances (TBARS), and fatty acids (FA). Higher temperatures and longer
      smoking times resulted in correspondingly lower quantities of oxidative products
      in the oils. Fatty acid methyl ester (FAME) analysis of smoke-processed oils
      confirmed that polyunsaturated fatty acids (PUFA) were not being destroyed. Smoke
      processing also imparted antioxidant potential to the extracted oils. Even when
      antioxidants, such as ethoxyquin or butylated hydroxytoluene, were added to raw
      oils, the smoke-processed oils still maintained lower levels of oxidation after
      14 d of storage. However, decreased antioxidant capacity of smoke-processed oils
      was noted when they were heated above 75 degrees C. Vitamin studies supported the
      antioxidant results, with smoke-processed oils displaying higher levels of alpha
      tocopherol than raw oils. Results suggest that smoking salmon prior to oil
      extraction can protect valuable PUFA-rich oils from oxidation. Improved
      preservation methods for marine oils may extend their usefulness when added as a
      supplement to enhance levels of eicosapentaenoic acid (EPA) and docosahexaenoic
      acid (DHA) in foods.

PMID- 19397711
TI  - Phenolic content and antioxidant activity of Primitivo wine: comparison among
      winemaking technologies.
AB  - The aim of this study was to assess the influence of 9 winemaking technologies
      (traditional, delestage, saignee, delayed punching-down, addition of grape seed
      tannins, addition of ellagic-skin-seed tannins, heating of must-wine, cryo
      maceration, and prolonged maceration) on the phenolic content and antioxidant
      activity of Primitivo musts and wines. Three methods for the determination of the
      antioxidant activity were compared: DPPH, beta-carotene bleaching assay, and
      ABTS. Oenological parameters and composition of the phenolic fraction of 1-y-aged
      wines was also determined. The addition of tannins allowed the increase of the
      phenolic content of musts and wines in a greater amount than the other
      technologies. The results concerning the antioxidant activity depended on the
      method applied. Concerning musts, the DPPH assay did not highlight great
      differences among technologies, whereas the addition of tannins allowed the
      obtainment of the highest antioxidant activity according to beta-carotene and
      ABTS assays. The wine aging determined an increase of the antioxidant activity,
      independently on the method applied. Wine obtained through traditional
      technology, saignee, and addition of tannins showed the highest antioxidant
      activities according to DPPH and beta-carotene. The highest correlation
      coefficients (0.961 and 0.932) were calculated between phenolic content and ABTS
      values of musts whereas the lowest values (0.413 and 0.517) were calculated
      between phenolic content and ABTS values of wines. Wines produced through
      traditional technology were the richest in anthocyanins. The addition of tannins
      allowed to obtain high content in monomeric anthocyanins, flavonoids, flavans
      reactive to vanillin, and coumaroylated malvidin and a low content in acetylated
      malvidin. Practical Applications: It is well known that a moderate consumption
      (equivalent to 2 glasses per day) of red wine is actually recommended since it
      appears associated with a decreased incidence of cardiovascular diseases. The
      mechanisms involved in this protective effect are not completely understood
      although they appear related to the presence of phenolic compounds. To increase
      the intake of these compounds without increase of the wine consumption, it is
      necessary to improve their extraction during maceration. This study could
      represent a helpful tool for wineries aimed to know the way to increase the
      antioxidant content of their wines, thus changing them in functional beverages
      and prolonging their shelf life.

PMID- 19397712
TI  - Antioxidant activities of purple rice bran extract and its effect on the quality
      of low-NaCl, phosphate-free patties made from channel catfish (Ictalurus
      punctatus) belly flap meat.
AB  - Purple rice bran contains high amounts of natural antioxidants that consist of
      water- and lipid-soluble compounds. Hexane-insoluble and hexane-soluble fractions
      were separated from 100% methanolic extract from purple rice bran (RBE-HI and RBE
      HS, respectively). Total anthocyanin, tannin, flavonoid, and phenolics contents
      were determined in those fractions, and their antioxidant capacities were
      evaluated by measuring 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging
      capability, oxygen radical absorbance capacity (ORAC), and iron chelating
      capability (ICC). RBE-HI and RBE-HS were also added to restructured patties made
      from minced channel catfish (Ictalurus punctatus) belly flap meat. Lipid
      oxidation, color, and/or textural properties were determined for raw and cooked
      patties during a 12-d storage at 4 degrees C. All antioxidant indices, except for
      ICC, of RBE-HI were significantly higher than those of RBE-HS due probably to its
      higher anthocyanin content (P < 0.05). RBE-HS showed higher ICC (P < 0.05).
      However, both fractions showed similar antioxidant activity in raw and cooked
      patties during storage, resulting from the complexity of antioxidant action in
      food systems. Textural properties (hardness, cohesiveness, chewiness, and
      springiness) in cooked patties with RBE-HS and RBE-HI were well maintained during
      storage, but changed significantly in the control (P < 0.05). Only RBE-HS limited
      microbial growth in raw patties during storage (P < 0.05), but its inhibitory
      effect was marginal because of low-dose and physical interactions with the
      matrix. L* (lightness) and a* (redness) of raw and cooked patties decreased
      significantly by both fractions, whereas b* (yellowness) was significantly
      decreased by RBE-HI and increased by RBE-HS (P < 0.05). In conclusion, we suggest
      that purple rice bran extract is applicable to meat products as a natural
      preservative, but color change in the products may limit its application.

PMID- 19397713
TI  - Using ozonation and amino acids to change pasting properties of rice starch.
AB  - In this study, the effects of ozonation and the addition of amino acids on rice
      starches were determined in terms of pasting properties using a rapid visco
      analyzer. Results from viscosity analysis showed that 30-min ozone treatment on
      commercial rice starch exhibited the greatest swelling extent among the
      treatments and least retrogradation tendency. The control pure oxygen treated
      sample had the best cooking stability. The addition of lysine (6%) to 30-min
      ozonated commercial rice starch significantly reduced peak viscosity (PV),
      minimum viscosity (MV), and final viscosity (FV) by 918, 1024, and 1023 cP,
      respectively. Moreover, it decreased Ptime, resulting in the faster swelling upon
      heating and less rigid gel formation upon cooling. Furthermore, the presence of
      lysine in 30-min ozonated starch isolate (WSI) also significantly reduced PV, MV,
      FV, pasting time, and total setback (TSB) and produced starch gel with the best
      cooking stability and the least retrogradation tendency. Ozonated starch
      exhibited similar pasting properties to those from oxidized starches treated with
      low concentrations of chemical oxidizing agents. The combination of lysine with
      ozonation resulted in pasting properties similar to starches treated with high
      levels of chemical oxidizing agents. The ozonated starch could be used as a
      thickening agent, whereas ozonated starch with lysine might be an alternative for
      a highly chemically oxidized starch. Therefore, ozonation alone or the
      combination of ozonation and addition of lysine might be used to develop new
      starch ingredients with various functionalities without using typical chemical
      modifications.

PMID- 19397714
TI  - Comparative study of washing treatments and alkali extraction on gelation
      characteristics of striped catfish (Pangasius hypophthalmus) muscle protein.
AB  - The effect of washing treatments (water and alkali washing) and alkali
      extraction/acid precipitation on the physicochemical and textural properties of
      striped catfish (Pangasius hypophthalmus) muscle protein was compared. Alkali
      extraction/acid precipitation process resulted in the highest protein recovery of
      98.77% (dry weight basis) and lowest fat content of 0.98% (dry weight basis). The
      extractable proteins of fish protein isolates (FPI) at various ionic strengths (0
      to 0.6 M NaCl) exhibited majority of protein at 38 kDa with trace amount of
      others. Unsaturated fatty acids, namely, oleic, linoleic, and docosahexaenoic
      acid, were greatly reduced in FPI. Water-washed mince (W) exhibited higher
      autolytic activity than mince (M), suggesting the presence of myofibril-bound
      proteinase(s). Autolytic activity was lowest in the FPI. Breaking force of
      striped catfish gels was greatly improved when set at 40 degrees C for 30 min,
      regardless of preparation treatment. The typical water washing process was
      effective to improve gel-forming ability of striped catfish. FPI gels contained
      the lower total sulfhydryl content, indicating the greater extent of disulfide
      bond formation as compared to that of washed mince. The FPI gels showed higher
      breaking force but lower deformation values than W and alkali-washed (AW) gels.
      Addition of NaCl improved deformation, but adversely affected breaking force of
      FPI gel. Whiteness of FPI gel increased with NaCl addition.

PMID- 19397715
TI  - Rapid prediction of composition and flavor quality of cheddar cheese using ATR
      FTIR spectroscopy.
AB  - Multiple methods are required for analysis of cheese flavor quality and
      composition. Chromatography and sensory analyses are accurate but laborious,
      expensive, and time consuming. A rapid and simple instrumental method based on
      Fourier transform infrared (FTIR) spectroscopy was developed for simultaneous
      analysis of Cheddar cheese composition and flavor quality. Twelve different
      Cheddar cheese samples ripened for 67 d were obtained from a commercial cheese
      manufacturer along with their moisture, pH, salt, fat content, and sensory flavor
      quality data. Water-soluble components were extracted from the cheese, dried on
      zinc selenide FTIR crystal and scanned (4000 to 700 cm(-1)). Infrared spectra of
      the samples were correlated with their composition and flavor quality data to
      develop multivariate statistical regression and classification models. The models
      were validated using an independent set of ten 67-d-old test samples. The
      infrared spectra of the samples were well defined, highly consistent within each
      sample and distinct from other samples. The regression models showed excellent
      fit (r > 0.92) and could accurately determine moisture, pH, salt, and fat
      contents as well as the flavor quality rating in less than 20 min. Furthermore,
      cheeses could also be classified based on their flavor quality (slight acid, whey
      taint, good cheddar, and so on). The discrimination of the samples was due to
      organic acids, amino acids, and short chain fatty acids (1800 to 900 cm(-1)),
      which are known to contribute significantly to cheese flavor. The results show
      that this technique can be a rapid, inexpensive, and simple tool for predicting
      composition and flavor quality of cheese.

PMID- 19397716
TI  - Extraction, identification, and quantification of flavonoids and phenolic acids
      in electron beam-irradiated almond skin powder.
AB  - The effect of electron beam irradiation doses from 0 to 30 kGy on extraction
      yield and phenolic compounds was evaluated in almond skin phenolic extracts
      (ASPE). Total soluble phenols and distribution of phenolic compounds from
      acidified methanol ASPE and 52% methanol ASPE were quantified using Folin
      Ciocalteau method, liquid chromatography with diode array and fluorescence
      detection, and negative ion electrospray-mass spectrometry. Electron beam
      irradiation increased extraction yield by as much as 23%, with the greatest
      increase observed in the acidified methanol ASPE. Irradiated samples extracted
      with acidified methanol also exhibited an increase in extractable phenols (Folin
      Ciocalteau) and total HPLC-resolved phenolics at all irradiation doses. Samples
      extracted with 52% methanol exhibited an increase at 10 and 20 kGy, but a 31%
      decrease at 30 kGy. An increase in aglycones respective to their glycosides was
      not observed with irradiation. Therefore, the increase in phenolics was
      attributed to release of phenolics from their cellular matrix.

PMID- 19397717
TI  - Characteristics of bread prepared from wheat flours blended with various kinds of
      newly developed rice flours.
AB  - Characteristics of the bread prepared from wheat flour blended with the flour of
      various kinds of newly developed rice cultivars were investigated. Qualities of
      the bread made from wheat flour blended with rice flour have been reported to be
      inferior to those from 100% wheat flour bread. To improve its qualities, we
      searched for the new-characteristic rice flours among the various kinds of newly
      developed rice cultivars to blend with the wheat flour for the bread preparation.
      The most suitable new characteristic rices are combination of purple waxy rice,
      high-amylose rice, and sugary rice. Specific volume of the bread from the
      combination of wheat and these 3 kinds of rice flours showed higher specific
      volume (3.93) compared with the traditional wheat/rice bread (3.58). We adopted
      the novel method, continuous progressive compression test, to measure the
      physical properties of the dough and the bread in addition to the sensory
      evaluation. As a result of the selection of the most suitable rice cultivars and
      blending ratio with the wheat flour, we could develop the novel wheat/rice bread,
      of which loaf volume, physical properties, and tastes are acceptable and
      resistant to firming on even 4 d after the bread preparation. To increase the
      ratio of rice to wheat, we tried to add a part of rice as cooked rice grains. The
      specific volume and qualities of the bread were maintained well although the rice
      content of total flour increased from 30% to 40%.

PMID- 19397718
TI  - Charged ultrafiltration membranes increase the selectivity of whey protein
      separations.
AB  - Ultrafiltration is widely used to concentrate proteins, but fractionation of one
      protein from another is much less common. This study examined the use of
      positively charged membranes to increase the selectivity of ultrafiltration and
      allow the fractionation of proteins from cheese whey. By adding a positive charge
      to ultrafiltration membranes, and adjusting the solution pH, it was possible to
      permeate proteins having little or no charge, such as glycomacropeptide, and
      retain proteins having a positive charge. Placing a charge on the membrane
      increased the selectivity by over 600% compared to using an uncharged membrane.
      The data were fit using the stagnant film model that relates the observed sieving
      coefficient to membrane parameters such as the flux, mass transfer coefficient,
      and membrane Peclet number. The model was a useful tool for data analysis and for
      the scale up of membrane separations for whey protein fractionation.

PMID- 19397719
TI  - Optimization of gluten-free formulations for French-style breads.
AB  - The formulation of gluten-free bread, which will be suitable for patients with
      coeliac disease, was optimized to provide bread similar to French bread. The
      effects of the presence of hydrocolloids and the substitution of the flour basis
      by flour or proteins from different sources were studied. The added ingredients
      were (1) hydrocolloids (carboxymethylcellulose [CMC], guar gum,
      hydroxypropylmethylcellulose [HPMC], and xanthan gum), and (2) substitutes
      (buckwheat flour, whole egg powder, and whey proteins). The bread quality
      parameters measured were specific volume, dry matter of bread, crust color, crumb
      hardness, and gas cell size distribution. Specific volume was increased by guar
      gum and HPMC. Breads with guar gum had color characteristics similar to French
      bread. Hardness decreased with the addition of hydrocolloids, especially HPMC and
      guar. Breads with guar gum had the most heterogeneous cell size distribution, and
      guar gum was therefore selected for further formulations. Bread prepared with
      buckwheat flour had improved quality: an increased specific volume, a softer
      texture, color characteristics, and gas-cell size distribution similar to French
      bread. Bread with 1.9% guar gum (w/w, total flour basis) and 5% buckwheat flour
      (of all flours and substitutes) mimicked French bread quality attributes.

PMID- 19397720
TI  - Nondestructive analysis of salt, water, and protein in dried salted cod using
      computed tomography.
AB  - Computed X-ray tomography (CT) was used to determine NaCl, water, and protein
      levels in dried salted cod. Cod fillets were salted and dried, and CT was
      conducted several times during the process. Also, homogenized cod samples with a
      chemical composition covering the typical composition of cod during salting and
      drying were produced, and CT scanned. Chemical composition of fillet and model
      samples was predicted from CT images acquired at 80, 110, and 130 kV. The best
      average prediction errors (RMSECV) obtained for homogenized samples were 0.6%
      NaCl, 1.3% water, and 1.5% protein; all explained variances were R2= 0.99 or
      above. The best RMSECVs and explained variances for cod fillet samples were 0.9%
      NaCl (R2= 0.96), 0.8% water (R2= 0.99), and 1.4% protein (R2= 0.79). Combining CT
      values from 2 or 3 voltages gave the best predictions except when predicting salt
      in cod fillet, where 1 voltage was sufficient.

PMID- 19397721
TI  - Detection of fecal residue on poultry carcasses by laser-induced fluorescence
      imaging.
AB  - Feasibility of fluorescence imaging technique for the detection of diluted fecal
      matters from various parts of the digestive tract, including colon, ceca, small
      intestine, and duodenum, on poultry carcasses was investigated. One of the
      challenges for using fluorescence imaging for inspection of agricultural material
      is the low fluorescence yield in that fluorescence can be masked by ambient
      light. A laser-induced fluorescence imaging system (LIFIS) developed by our group
      allowed acquisition of fluorescence from feces-contaminated poultry carcasses in
      ambient light. Fluorescence emission images at 630 nm were captured with 415-nm
      laser excitation. Image processing algorithms including threshold and image
      erosion were used to identify fecal spots diluted up to 1: 10 by weight with
      double distilled water. Feces spots on the carcasses, without dilution and up to
      1: 5 dilutions, could be detected with 100% accuracy regardless of feces type.
      Detection accuracy for fecal matters diluted up to 1: 10 was 96.6%. The results
      demonstrated good potential of the LIFIS for detection of diluted poultry fecal
      matter, which can harbor pathogens, on poultry carcasses.

PMID- 19397722
TI  - Extraction and physicochemical characterization of greater Lizardfish (Saurida
      tumbil) skin and bone gelatin.
AB  - Type A gelatins were extracted from skins and bones of lizardfish and analyzed to
      determine their functional and chemical properties. Lizardfish skin gelatin had
      ash content of 2.2 +/- 0.3% while bone gelatin had ash content of 12.2 +/- 0.2%.
      Gel strength was 159.1 +/- 14 and 135 +/- 7.9 g, respectively, for skin and bone
      gelatins compared to 224.3 +/- 7.7 g for porcine gelatin. Gelatin from skin
      exhibited higher viscosity and lower setting time than bone. Skin gelatin had
      higher imino acid content than bone gelatin. The total imino acid content was
      21.71% and 19.83% for skin and bone, respectively. Both skin and bone gelatins
      contained more alpha chains than beta and gamma components. Both bone and skin
      gelatins also contained low molecular weight (< alpha) peptides. The differences
      in functional properties between the skin and bone gelatins appeared to be
      related to differences in amino acid composition and molecular weight
      distribution of the gelatins.

PMID- 19397724
TI  - Influence of cooking methods on antioxidant activity of vegetables.
AB  - The influence of home cooking methods (boiling, microwaving, pressure-cooking,
      griddling, frying, and baking) on the antioxidant activity of vegetables has been
      evaluated in 20 vegetables, using different antioxidant activity assays
      (lipoperoxyl and hydroxyl radicals scavenging and TEAC). Artichoke was the only
      vegetable that kept its very high scavenging-lipoperoxyl radical capacity in all
      the cooking methods. The highest losses of LOO. scavenging capacity were observed
      in cauliflower after boiling and microwaving, pea after boiling, and zucchini
      after boiling and frying. Beetroot, green bean, and garlic kept their antioxidant
      activity after most cooking treatments. Swiss chard and pepper lost OH.
      scavenging capacity in all the processes. Celery increased its antioxidant
      capacity in all the cooking methods, except boiling when it lost 14%. Analysis of
      the ABTS radical scavenging capacity of the different vegetables showed that the
      highest losses occurred in garlic with all the methods, except microwaving. Among
      the vegetables that increased their TEAC values were green bean, celery, and
      carrot after all cooking methods (except green bean after boiling). These 3 types
      of vegetables showed a low ABTS radical scavenging capacity. According to the
      method of analysis chosen, griddling, microwave cooking, and baking alternately
      produce the lowest losses, while pressure-cooking and boiling lead to the
      greatest losses; frying occupies an intermediate position. In short, water is not
      the cook's best friend when it comes to preparing vegetables.

PMID- 19397723
TI  - High-hydroxypropylated tapioca starch improves insulin resistance in genetically
      diabetic KKAy mice.
AB  - The hypoglycemic and antidiabetic effect of hydroxypropyl tapioca starch (HPTS)
      with a varying degree of substitution (DS: 0.058, 0.091, and 0.180) was
      investigated in rats and KKAy mice, an animal model of type 2 diabetes. The
      positive incremental area under the curve (IAUC) for glucose significantly
      decreased as the DS of HPTS increased. The IAUC after intragastric intubation of
      the highest HPTS (HPTS-III, DS = 0.180) was 55% of the IAUC of tapioca starch
      (TS). After 28 d, fasting blood glucose and insulin concentrations were
      significantly lower in rats fed HPTS-III (50 g/kg diet) than in those fed TS (P <
      0.05). In KKAy mice fed HPTS-III (50 or 100 g/kg diet) for 33 d, as compared with
      TS, there was a delay in the detection of glucose in urine and also a decreased
      incidence of finding glucose in urine on days 7, 21, and 28; in addition, the
      AUCs for glucose in the oral glucose tolerance test on days 14 and 28 were
      significantly lower (P < 0.05 and P < 0.05, respectively). The plasma adiponectin
      concentration and the quantitative insulin sensitivity check index (QUICKI) were
      significantly higher in mice fed HPTS-III than in those fed TS (P < 0.01),
      whereas the homeostasis model assessment of insulin resistance (HOMA-IR) was
      lower (P < 0.01). Energy intake was significantly lower in mice fed HPTS-III than
      in those fed TS. These findings show that HPTS with a high DS resists digestion
      by alpha-amylase and improves insulin resistance in KKAy mice by decreasing
      energy intake. However, the potential mechanism by which HPTS-III decreases
      energy intake is unclear at present.

PMID- 19397725
TI  - Effects of ionizing radiation on microbial decontamination, phenolic contents,
      and antioxidant properties of triphala.
AB  - Triphala, a mixture of Emblica officinalis, Terminalia chebula, and Terminalia
      bellirica, containing ingredients from plant origin, is often prone to microbial
      contamination. A high level of microbial contamination was observed in Triphala
      samples obtained from different sources. On gamma radiation processing, a sharp
      decline in log CFU was observed with increasing radiation dose and a complete
      decontamination at 5 kGy. Average D10 value for total aerobic and fungal counts
      were observed to be 0.55 +/- 0.073 kGy and 0.94 +/- 0.043 kGy, respectively.
      Water extracts of irradiated samples showed linearly increasing concentration of
      gallic acid (3.3 to 4.5 times), total phenolic contents (2.16 to 2.87 times), and
      antioxidant properties with increasing radiation dose up to 25 kGy. The increase
      could be attributed to easy release of active ingredients from their radiation
      degraded complex forms. Aflatoxin B(1) and ochratoxin could not be detected in
      the samples. Gamma-radiation dose up to 5 kGy could be safely used to hygienize
      Triphala.

PMID- 19397726
TI  - Ultraviolet light (254 nm) inactivation of Listeria monocytogenes on frankfurters
      that contain potassium lactate and sodium diacetate.
AB  - Listeria monocytogenes, a psychrotrophic foodborne pathogen, is an occasional
      postprocess contaminant on ready-to-eat meat (RTE) products including
      frankfurters. Ultraviolet C light (UVC) is an FDA-approved technology for the
      decontamination of food surfaces. In this study, the ability of UVC to inactivate
      L. monocytogenes on frankfurters that contained potassium lactate (PL) and sodium
      diacetate (SDA), either before or after packaging, was investigated. UVC
      irradiation of frankfurters that were surface-inoculated with L. monocytogenes
      resulted in a 1.31, 1.49, and 1.93 log reduction at doses of 1, 2, and 4 J/cm(2),
      respectively. UVC treatment had no effect on frankfurter color or texture at UVC
      doses up to 4 J/cm(2). Frankfurter meat treated with UVC doses up to 16 J/cm(2)
      did not increase mutagenesis in bacterial or human cells, either with or without
      exogenous metabolic activation. UVC treatment of single-layer frankfurter packs
      at a dose of 2 J/cm(2) resulted in a 0.97 (+/- 0.14) log reduction of L.
      monocytogenes. Following 8 wk of refrigerated storage L. monocytogenes levels
      decreased by only 0.65 log in non-UVC-treated frankfurter packs compared with 2.5
      log in the UVC-treated packs. Because the numbers of L. monocytogenes associated
      with contaminations of ready-to-eat meats are typically very low, the use of UVC
      in combination with potassium lactate and sodium diacetate has the potential to
      reduce the number of frankfurter recalls and foodborne illness outbreaks.

PMID- 19397727
TI  - Sporulation and germination gene expression analysis of Bacillus anthracis Sterne
      spores in skim milk under heat and different intervention techniques.
AB  - To investigate how B. anthracis Sterne spores survive in milk under heat (80
      degrees C, 10 min), pasteurization (72 degrees C, 15 s), microfiltration, and
      pasteurization and microfiltration, the expression levels of genes related to
      sporulation and germination were tested using real-time PCR assays. Twenty-seven
      sporulation- and germination-related genes were selected for the target genes.
      Our results demonstrated that gene expression levels were altered by heat and
      microfiltration whereas the pasteurization and pasteurization and microfiltration
      resulted in less alteration of gene expression. Heat activated and inhibited both
      sporulation- and germination-related genes, suggesting that bacterial spores
      underwent different molecular mechanism for heat treatments. Our results may
      provide some insight into the molecular mechanisms of spore survival in response
      to heat treatment and different intervention strategies used to treat fluid skim
      milk.

PMID- 19397728
TI  - Modeling the growth characteristics of Listeria monocytogenes and native
      microflora in smoked salmon.
AB  - Smoked salmon contaminated with Listeria monocytogenes has been implicated in
      foodborne listeriosis. The objectives of this study were to model the growth
      characteristics and examine the growth relationship of L. monocytogenes and
      native microflora in smoked salmon. Smoked salmon samples with a native
      microflora count of 2.9 log(10) CFU/g were inoculated with a 6-strain mixture of
      L. monocytogenes to levels of log(10) 1.6 and log(10) 2.8 CFU/g, and stored at 4,
      8, 12, and 16 degrees C. Growth characteristics (lag phase duration [LPD, h],
      growth rate [GR, log(10) CFU/h], and maximum population density [MPD, log(10)
      CFU/g]) of L. monocytogenes and native microflora were determined. At 4 to 16
      degrees C, the LPD, GR, and MPD were 254 to 35 h, 0.0109 to 0.0538 log(10) CFU/h,
      and 4.9 to 6.9 log(10) CFU/g for L. monocytogenes, respectively, and were 257 to
      29 h, 0.0102 to 0.0565 log(10) CFU/h, and 8.5 to 8.8 log(10) CFU/g for native
      microflora. The growth characteristics of L. monocytogenes or the native
      microflora were not significantly different (P > 0.05), regardless the initial
      levels of L. monocytogenes. Mathematical equations were developed to describe the
      LPD, GR, and MPD of L. monocytogenes and native microflora as a function of
      storage temperature. The growth relationship between L. monocytogenes and native
      microflora was modeled and showed that the LPD and GR of L. monocytogenes were
      similar to those of native microflora. These models can be used to estimate the
      growth characteristics of L. monocytogenes in smoked salmon, and thereby enhance
      the microbiological safety of the product.

PMID- 19397729
TI  - Antimicrobial efficiency of essential oil and freeze-thaw treatments against
      Escherichia coli O157:H7 and Salmonella enterica Ser. Enteritidis in strawberry
      juice.
AB  - This study investigated the antimicrobial efficiency of 3 essential oils (EOs),
      lemongrass, cinnamon leaf, and basil, and freeze-thaw treatment, alone or in
      combination, against Escherichia coli O157:H7 and Salmonella enterica Ser.
      Enteritidis inoculated in strawberry juice stored at 7 degrees C. EO of
      lemongrass or cinnamon leaf at 0.1 to 2 microL/mL and freezing at -23 degrees C
      for 24 or 48 h followed by thawing at 7 degrees C for 4 h all showed significant
      antimicrobial activities (P < 0.05) against E. coli O157:H7 and S. Enteritidis in
      strawberry juice. The antimicrobial activity increased with increasing EO
      concentration and storage time, but extending freezing time from 24 to 48 h did
      not enhance the antimicrobial activity of freeze-thaw treatment (P > 0.05). EO of
      lemongrass or cinnamon leaf at 0.1 microL/mL and freeze-thaw treatment alone
      obtained a 5 log(10) reduction in the population of S. Enteritidis, while EOs at
      0.1 to 0.3 microL/mL or freeze-thaw alone could not achieve a satisfactory
      protection against E. coli O157:H7 in strawberry juice. Combined EO and freeze
      thaw treatment enhanced the overall antimicrobial effect against E. coli O157:H7,
      with adding EO before the freeze-thaw treatment showed a faster decontamination
      rate than when added EO after the freeze-thaw. EOs of lemongrass and cinnamon
      leaf at 0.1 or 0.3 microL/mL followed by the freeze-thawing resulted in a 5
      log(10) reduction in E. coli O157:H7 on the 5th and 2nd day of storage,
      respectively. This study suggested that combined EO and freeze-thaw treatment may
      be a suitable and inexpensive method to eliminate microorganisms that can be a
      hazard for the consumers of unpasteurized berry juices.

PMID- 19397730
TI  - Inactivation of Listeria innocua on frankfurters by ultraviolet light and flash
      pasteurization.
AB  - Listeria monocytogenes, a psychrotrophic foodborne pathogen, is a recurring
      postprocess contaminant on ready-to-eat meat (RTE) products including
      frankfurters. Flash (Steam) Pasteurization (FP) and ultraviolet light (254 nm
      UVC) has been shown to reduce levels of L. monocytogenes and L. innocua on
      frankfurters. In this study, the use of UVC light followed by FP to inactivate L.
      innocua, a nonpathogenic surrogate for L.monocytogenes, on frankfurters that
      contained sodium diacetate and potassium lactate (SDA/PL) in a pilot-plant
      setting was investigated. Application of UVC (1.0 J/cm2), followed by FP (0.75 s
      steam/121 degrees C) resulted in inactivation of 3.19 log L. innocua, while
      application of UVC (4.0 J/cm2), followed by FP (3 s steam/121 degrees C) resulted
      in inactivation of 3.89 log of L. innocua. A refrigerated storage study (8
      degrees C) of frankfurters that contained SDA/PL that were treated with UVC
      followed by FP revealed the growth of L. innocua was inhibited for approximately
      8 wk following application of the interventions. The use of UVC in combination
      with FP had little effect on frankfurter color and texture. The combination of
      UVC, FP, and SDA/PL was found to be an effective hurdle process for
      decontamination of frankfurter surfaces.

PMID- 19397732
TI  - Relationship between muscle pH and flesh color of Atlantic halibut.
AB  - After 7 d of ice storage, the muscle pH and flesh color (CIE L*, a*, b*) was
      measured in 118 Atlantic halibut (Hippoglossus hippoglossus) slaughtered at
      different times of the year. All fish originated from the same stock and the fish
      were farmed under natural and continuous light and slaughtered fed or starved,
      representing a wide distribution of fish undergoing different stages of growth,
      maturation, and sizes (1.5 to 5.9 kg). Results show a considerable variation of
      end pH ranging from 5.7 to 6.8. The color correlated significantly with muscle pH
      with R = -0.63, 0.61, and -0.57 for L*, a*, and b*, respectively, while fillet
      weight and sampling position on the fillet had less influence on color. We
      conclude that the end pH of the muscle is an important factor for the visual
      quality of fish, and in particular for Atlantic halibut. Therefore, measures
      should be taken to avoid high glycogen levels at death, as this will have a large
      impact on the muscle pH, with negative consequences for flesh color.

PMID- 19397731
TI  - Factors affecting rheological characteristics of fibril gels: the case of beta
      lactoglobulin and alpha-lactalbumin.
AB  - Some of the factors that affect the rheological characteristics of fibril gels
      are discussed. Fibrils with nanoscale diameters from beta-lactoglobulin (beta-lg)
      and alpha-lactalbumin (alpha-la) have been used to create gels with different
      rheological characteristics. Values of the gelation time, t(c), the critical gel
      concentration, c(0), and the equilibrium value of the storage modulus, G, such as
      at long gelation times, derived from experimental rheological data, are
      discussed. Fibrils created from beta-lg using solvent incubation and heating
      result in gels with different rheological properties, probably because of
      different microstructures and fibril densities. Partial hydrolysis of alpha-la
      with a serine proteinase from Bacillus licheniformis results in fibrils that are
      tubes about 20 nm in diameter. Such a fibril gel from a 10% (w/v) alpha-la
      solution has a higher modulus than a heat-set gel from a 10% (w/w) beta-lg, pH
      2.5 solution; it is suggested that one reason for the higher modulus might be the
      greater stiffness of alpha-la fibrils. However, the gelation times of alpha-la
      fibrils are longer than those of beta-lg fibrils.

PMID- 19397733
TI  - Quality index, consumer acceptability, bioactive compounds, and antioxidant
      activity of fresh-cut "ataulfo" mangoes (mangifera indica L.) as affected by low
      temperature storage.
AB  - To measure bioactive compound losses due to minimal processing, mature green
      fresh-cut mangoes (Mangifera indica L.) cv. "Ataulfo" were subjected to an
      antioxidant treatment and stored at 5 degrees C during 15 d. Quality index, total
      phenols, flavonoids, beta-carotene, ascorbic acid, vitamin E, and antioxidant
      activity were measured during the storage period of fruits. Antioxidant capacity
      was estimated using ORAC(FL), TEAC, and DPPH assays. The dipping treatments with
      ascorbic acid (AA) + citric acid (CA) + CaCl2 affected positively quality
      delaying deterioration of fresh-cut mango as compared with whole fruit. However,
      dipping treatment affected the consumer preferences of fresh-cut mangoes. The
      highest vitamin C, beta-carotene, and vitamin E losses were observed after 10 d,
      being similar in whole and fresh-cut mangoes. The antioxidant activity was not
      significantly affected by storage time. We conclude that fresh-cut mangoes
      retained their bioactive compound content during storage and their antioxidant
      and nutritional properties make them a good source of these compounds.

PMID- 19397734
TI  - Sensory characteristics and consumer acceptability of decaffeinated green teas.
AB  - Green tea has been widely consumed for its mild flavors and its health benefits,
      yet caffeine in green tea has been a limitation for those who want to avoid it.
      The limitation brought increase in need for decaffeinated products in the green
      tea market. Most of the conventional decaffeination techniques applied in food
      use organic solvents. However, supercritical carbon dioxide fluid extraction (SC
      CO2) method is gaining its intension as one of the future decaffeination methods
      that overcomes the problems of conventional methods. The purpose of this study
      was to identify sensory characteristics of decaffeinated green teas applied with
      SC-CO2 method and to observe the relationship with consumer acceptability to
      elucidate the potentiality of applying SC-CO2 technique in decaffeinated green
      tea market. Descriptive analysis was performed on 8 samples: green teas
      containing 4 caffeine levels (10%, 35%, 60%, and 100%) infused at 2 infusing
      periods (1 or 2 min). It was found that the SC-CO2 process not only reduced
      caffeine but also decreased some important features of original tea flavors. Two
      groups were recruited for consumer acceptability test: one (GP I, N = 52),
      consuming all types of green teas including hot/cold canned teas; and the other
      (GP II, N = 40), only consuming the loose type. While GP II liked original green
      tea the most, GP I liked highly decaffeinated green teas. Although the SC-CO2
      method had limitations of losing complex flavors of green teas, it appeared to
      have future potential in the decaffeinated green tea market within or without the
      addition of desirable flavors.

PMID- 19397735
TI  - Color development of squid skin as affected by oxygen concentrations.
AB  - Color development of squid skin was controlled by O2 concentration for storage.
      When stored above 10% O2, the color index (CI) as an index of color development
      of skin increased in 24 h, and decreased gradually with further storage. The CI
      profile at 10% O2 was practically identical to that in air. When stored at 0.1%
      O2, in the presence of N2, the CI increased partly in 6 h and decreased.
      Morphological observation of chromatophore distinguished the CI increase at 0.1%
      and 10% O2 by their shape and size distribution. However, the storage of squid at
      O2 concentration between 2.5% and 7% practically did not change the CI for at
      least 48 h. ATP content of skin was kept unchanged when the storage atmosphere
      contained O2 concentration at 2.5% up to 48 h, while the content decreased
      rapidly with a half decrease in 6 h when stored at 0.1% O2. It was demonstrated
      clearly that ATP is regenerated in the presence of O2, but the ATP concentration
      did not determine the CI change during the storage. Exposure to high
      concentration of O2 might induce a full color development of squid skin.

PMID- 19397738
TI  - Letter to the editor: salt in bread.

PMID- 19397739
TI  - Capsule-supporting ring: a new device for resin embedding of glass-mounted
      specimens.
AB  - The goal of specimen preparation for transmission electron microscopy is to
      obtain high-quality ultra-thin sections with which we can correlate cellular
      structure to physiological function. In this study, we newly developed a capsule
      supporting ring that can be useful for resin embedding of glass-mounted
      specimens. The present device allowed us to re-embed a semi-thin section on a
      microscope slide into a resin block not only for efficient ultra-thin sectioning
      but also for a correlative light and electron microscopy. Similar to epoxy resins
      for morphological observations, semi-thin sections of low-viscosity hydrophilic
      resins, such as Lowicryl series, can be re-embedded into the resin, which can be
      useful for cytochemical gold labelling. A further application of the present
      device improved flat embedding of cultured cells on glass cover slips for
      electron microscopy, preserving in situ sub-cellular structures close to their
      native state. We practically describe the use of capsule-supporting ring and
      demonstrate representative micrographs as results.

PMID- 19397740
TI  - Visualization of BrdU-labelled DNA in cyanobacterial cells by Hilbert
      differential contrast transmission electron microscopy.
AB  - We have attempted to observe the native shape of DNA in rapidly frozen whole
      cyanobacterial cells through 5-bromo-2-deoxyuridine (BrdU) incorporation and
      visualization with a Hilbert differential contrast transmission electron
      microscopy (HDC TEM). The incorporation of BrdU into the DNA of Synechococcus
      elongatus PCC 7942 was confirmed with fluorescently labelled anti-BrdU antibodies
      and through EDX analysis of ultra-thin sections. HDC TEM observed cells that had
      incorporated BrdU into their DNA exhibited electron dense areas at the location
      corresponding to fluorescently labelled BrdU. Since various strings and strands
      were observed in high contrast with the HDC TEM, we conclude that the method
      promises to allow us to identify and understand bulk structural changes of the in
      vivo DNA and the nucleoid through observation at high resolution.

PMID- 19397741
TI  - Assessment of acridine orange and SYTO 16 for in vivo imaging of the peritoneal
      tissues in mice.
AB  - The effect of peritoneal injection of acridine orange and SYTO 16 in mice was
      investigated. Images of peritoneal tissues stained with these dyes and obtained
      through a confocal micro-endoscope are presented. Seventy-five Balb/c mice were
      split into five groups and given peritoneal injections of dye or saline. The
      proportions of negative outcomes in each group were compared using confidence
      intervals and the Fisher's exact statistical test. A statistically significant
      increase in adverse events due to dye injection was not observed. These data
      provide an initial investigation into the safety of acridine orange and SYTO 16
      for in vivo imaging.

PMID- 19397742
TI  - Disassembly of DNA-ligand on mica surface: atomic force microscopy studies.
AB  - Disassembly of DNA-ligands, including DNA-methylene blue (MB) complex and DNA
      Co(phen)(3) (3+) complex on mica surface, were investigated by atomic force
      microscopy (AFM). The disassembly of these complexes occurred after they were
      immersed in ultra-pure water. AFM results showed that the disassembly depended
      strongly on bridge ions that were used to immobilize the complex onto mica
      surface, DNA species and ligands. When Mg(2+) was used as the bridge ion, the DNA
      MB complex was completely disassembled because of the weak interactions between
      Mg(2+) and DNA's bases or mica surface. Although if Co(2+) was used as the bridge
      ion, the disassembly of the DNA-MB complex mainly depended on the species and
      shape of DNA. For plasmid DNA pBR 322, plasmid DNA pUC 18 and the linear DNA pBR
      322/PstI, the degree of disassembly was gradually increased. Whereas if
      Co(phen)(3) (3+) was chosen as the ligand, the disassembly of the DNA-Co(phen)(3)
      (3+) complex was almost blocked because Co(phen)(3) (3+) could hardly diffuse
      into the ultra-pure water. This obtained information may be useful for practical
      application of the AFM imaging of biological molecules, especially in liquid.

PMID- 19397743
TI  - Extending immunofluorescence detection limits in whole paraffin-embedded formalin
      fixed tissues using hyperspectral confocal fluorescence imaging.
AB  - A major problem in microscopic imaging of ex vivo tissue sections stained with
      fluorescent agents (e.g. antibodies, peptides) is the confounding presence of
      background tissue autofluorescence. Autofluorescence limits (1) the accuracy of
      differentiating background signals from single and multiple fluorescence labels
      and (2) reliable quantification of fluorescent signals. Advanced techniques such
      as hyperspectral imaging and spectral unmixing can be applied to essentially
      remove this autofluorescent signal contribution, and this work attempts to
      quantify the effectiveness of autofluorescence spectral unmixing in a tumour
      xenograft model. Whole-specimen single-channel fluorescence images were acquired
      using excitation wavelengths of 488 nm (producing high autofluorescence) and 568
      nm (producing negligible autofluorescence). These single-channel data sets are
      quantified against hyperspectral images acquired at 488 nm using a prototype
      whole-slide hyperspectral fluorescence scanner developed in our facility. The
      development and further refinement of this instrument will improve the
      quantification of weak fluorescent signals in fluorescence microscopy studies of
      ex vivo tissues in both preclinical and clinical applications.

PMID- 19397744
TI  - Fast linear feature detection using multiple directional non-maximum suppression.
AB  - The capacity to detect linear features is central to image analysis, computer
      vision and pattern recognition and has practical applications in areas such as
      neurite outgrowth detection, retinal vessel extraction, skin hair removal, plant
      root analysis and road detection. Linear feature detection often represents the
      starting point for image segmentation and image interpretation. In this paper, we
      present a new algorithm for linear feature detection using multiple directional
      non-maximum suppression with symmetry checking and gap linking. Given its low
      computational complexity, the algorithm is very fast. We show in several examples
      that it performs very well in terms of both sensitivity and continuity of
      detected linear features.

PMID- 19397745
TI  - Geometric quantification of the plant endoplasmic reticulum.
AB  - One of the most difficult obstacles to make biological sciences more quantitative
      is the lack of understanding the interplay of form and function. Each cell is
      full of complex-shaped objects, which moreover change their form over time. To
      tackle this problem, we suggest the use of geometric invariants that are able to
      produce precise reference points to compare a cell's different functional
      elements such as organelles under fixed and varying physiological conditions. In
      this paper, we look at the topology of an almost static sample of the plant
      cortical endoplasmic reticulum (ER) under close-to-normal physiological
      conditions using a multi-disciplinary approach combining confocal microscopy,
      image processing techniques, visualization, computational geometry and graph
      theory. Data collected from a series of optical sections taken at short, regular
      intervals along the optical axis are used to reconstruct the ER in three
      dimensions. A graph structure of the ER network is obtained after thinning the ER
      geometry to its essential features. The graph is the final and most abstract
      quantification of the ER and serves very well as a geometrical invariant, even
      and very importantly, in cases in which the ER sample is moving or slightly
      changing shape during image acquisition. Moreover, graph theoretic features, such
      as the number of nodes and their degrees and the number of edges and their
      lengths, are very robust against different kinds of small perturbations that
      should not change the ER function. We will also attach surface areas and volumes
      estimated for the plant ER network as weights to the graph, allowing an even more
      precise quantitative characterization of this organelle. In total, we have
      compared 28 different samples under similar experimental conditions. The methods
      used in this paper should also be applicable to the quantification of other
      organelles in which geometric abstraction is possible to analyse function.
      Finally, by the use of confocal microscopy, our techniques will be transferable
      to situations in which protein markers can move inside the organelle's lumen
      and/or on the membrane surface to test further aspects of protein distribution.

PMID- 19397746
TI  - Measurements of the diameters of the great arteries and semi-lunar valves of
      chick and mouse embryos.
AB  - The great arteries of embryos are small channels of a complex three-dimensional
      arrangement. Measurements of their diameters, as required for understanding
      cardiovascular morphogenesis and the genesis of malformations, cannot be
      performed in two-dimensional histological sections. We present and evaluate a
      quick and simple method for performing highly significant and objective
      measurements of the diameters of blood vessels in vertebrate embryos and used
      this method for providing statistics of the diameter of the semi-lunar valves and
      the lumina of the great arteries of early chick and mouse foetus. We employed the
      high-resolution episcopic microscopy technique for generating volume data and
      three-dimensional computer models of the arterial trees of 30 chick embryos
      (Hamburger Hamilton stage 34), 30 mouse embryos of the OF1 strain harvested on
      14.5 dpc, 30 embryos of the OF1 strain harvested on 15.5 dpc and 28 mouse embryos
      of the PARKES strain harvested on 14.5 dpc. The three-dimensional models (voxel
      size 2 mum x 2 mum x 2 mum and 3 mum x 3 mum x 3 mum) were used for defining
      virtual resection planes perpendicular to the longitudinal axis of the blood
      vessels at comparable positions. In these planes, we measured the lumen areas and
      the lumen perimeters. We also calculated the lumen diameter and the true lumen
      area from the perimeter and present statistical analysis. Finally, we evaluate
      and discuss the reliability and reproducibility of our method and present all
      measurements in a form that minimizes the influence of specimen size variation,
      specimen processing and data generation methods.

PMID- 19397747
TI  - An improved dynamic model of tuning fork probe for scanning probe microscopy.
AB  - This paper presents a two coupled oscillators model to describe the dynamics of a
      tuning fork with a probe attached. The two coupled oscillators are unbalanced
      only in their effective masses and the damping ratios. By applying a frequency
      domain system identification approach in experimental investigation of various
      probe attachment cases, a good accuracy of the model is demonstrated. The
      effectiveness of the model is further demonstrated in quantitative analysis of
      the noise performance and the sensitivity of force sensing with a tuning fork
      probe. Compared with existing models, the proposed model can more accurately
      characterize the dynamics of a tuning fork probe.

PMID- 19397748
TI  - Preparation of wholemount mouse intestine for high-resolution three-dimensional
      imaging using two-photon microscopy.
AB  - Visualizing overall tissue architecture in three dimensions is fundamental for
      validating and integrating biochemical, cell biological and visual data from less
      complex systems such as cultured cells. Here, we describe a method to generate
      high-resolution three-dimensional image data of intact mouse gut tissue. Regions
      of highest interest lie between 50 and 200 mum within this tissue. The quality
      and usefulness of three-dimensional image data of tissue with such depth is
      limited owing to problems associated with scattered light, photobleaching and
      spherical aberration. Furthermore, the highest-quality oil-immersion lenses are
      designed to work at a maximum distance of </=10-15 mum into the sample, further
      compounding the ability to image at high-resolution deep within tissue. We show
      that manipulating the refractive index of the mounting media and decreasing
      sample opacity greatly improves image quality such that the limiting factor for a
      standard, inverted multi-photon microscope is determined by the working distance
      of the objective as opposed to detectable fluorescence. This method negates the
      need for mechanical sectioning of tissue and enables the routine generation of
      high-quality, quantitative image data that can significantly advance our
      understanding of tissue architecture and physiology.

PMID- 19397749
TI  - Two-colour two-photon confocal microscopy with isotropic three-dimensional
      resolution and parallel excitation.
AB  - We demonstrate a novel design of two-colour two-photon fluorescence microscope in
      which isotropic three-dimensional imaging resolution and high scanning speed can
      be achieved simultaneously. In our scheme, a three-dimensional optical lattice
      constructed by multi-beam interference is used for two-colour two-photon
      fluorescence excitation. Our simulation results show that a resolution of 113.5
      nm can be achieved in both transverse and axial directions with two pump pulses
      at the wavelengths of 400 and 800 nm, respectively; meanwhile, imaging speed can
      be greatly improved compared with that of traditional two-photon scanning
      fluorescence microscopes.

PMID- 19397750
TI  - AKINbeta1 is involved in the regulation of nitrogen metabolism and sugar
      signaling in Arabidopsis.
AB  - Sucrose non-fermenting-1-related protein kinase 1 (SnRK1) has been located at the
      heart of the control of metabolism and development in plants. The active SnRK1
      form is usually a heterotrimeric complex. Subcellular localization and specific
      target of the SnRK1 kinase are regulated by specific beta subunits. In
      Arabidopsis, there are at least seven genes encoding beta subunits, of which the
      regulatory functions are not yet clear. Here, we tried to study the function of
      one beta subunit, AKINbeta1. It showed that AKINbeta1 expression was dramatically
      induced by ammonia nitrate but not potassium nitrate, and the investigation of
      AKINbeta1 transgenic Arabidopsis and T-DNA insertion lines showed that AKINbeta1
      negatively regulated the activity of nitrate ruductase and was positively
      involved in sugar repression in early seedling development. Meanwhile AKINbeta1
      expression was reduced upon sugar treatment (including mannitol) and did not
      affect the activity of sucrose phosphate synthase. The results indicate that
      AKINbeta1 is involved in the regulation of nitrogen metabolism and sugar
      signaling.

PMID- 19397752
TI  - Effect of dexamethasone on respiratory syncytial virus-induced lung inflammation
      in children: results of a randomized, placebo controlled clinical trial.
AB  - Inflammatory mediators play a major role in the pathogenesis of respiratory
      syncytial virus (RSV) infection. The objective of this study was to evaluate the
      effect of i.v. dexamethasone on cytokine concentrations in tracheal aspirates
      (TA) of children with severe RSV disease and to correlate them with disease
      severity. Twenty-five cytokines were measured in TA obtained from children <2 yr
      old intubated for severe RSV disease, and enrolled in a double-blind study of
      i.v. dexamethasone (0.5 mg/kg; n = 22) vs. placebo (n = 19). Cytokine
      concentrations, measured at baseline and days 1 and 5 post-randomization using a
      multiplex assay, were compared within both treatment groups and correlated with:
      (i) tracheal white blood cell counts, (ii) tracheal RSV loads by culture and
      (iii) parameters of disease severity, including number of days of requirement for
      mechanical ventilation, intensive care unit (ICU), and hospitalization. At
      baseline interleukin (IL)-13 and IL-15 concentrations were significantly higher
      in the dexamethasone treatment group. On day 1 post-treatment, only MCP-1,
      eotaxin and IL-6 concentrations were significantly different but higher in the
      placebo group. On day 5: IL-13, IL-7, IL-8 and MIP-1alpha concentrations were
      higher in dexamethasone-treated patients. In both groups MIP-1beta inversely
      correlated with the days of ventilator support; MIP-1alpha, MIP-1beta and eotaxin
      inversely correlated with ICU days; and IL-6 inversely correlated with
      hospitalization regardless of the treatment assigned. Systemic administration of
      dexamethasone did not have a consistent effect on TA concentrations of pro
      inflammatory cytokines. This may help explain, at least in part, the lack of
      clinical benefit of steroid treatment in children with severe RSV bronchiolitis.

PMID- 19397753
TI  - Cow's milk allergy is associated with changes in urinary organic acid
      concentrations.
AB  - Cow's milk allergy (CMA) is the most common form of food allergy affecting 2.5%
      of children, but the diagnosis is often difficult. Both intestinal microbiota and
      barrier function seem to be disturbed in patients with food allergies, and
      administration of probiotics has been shown to normalize intestinal microbiota
      and alleviate symptoms. We hypothesized that the differences in intestinal
      metabolic activity and permeability could lead to detectable changes in the end
      products of metabolism in patients with CMA. This could offer new diagnostic
      possibilities. The urinary concentrations of 37 organic acids were studied by a
      mass spectrometry-based method in 35 infants aged under 1 yr with atopic eczema,
      16 of them having CMA diagnosed with a double-blind placebo-controlled food
      challenge test. The control group consisted of the remaining 19 infants with only
      atopic eczema. In a second study, Lactobacillus rhamnosus GG (LGG) or placebo was
      administered to the infants with CMA for 4 wk and the urinary organic acids were
      analysed again. CMA patients and patients with only atopic eczema had
      statistically significant differences in urinary concentrations of
      hydroxybutyrate (p<0.001); adipate and isocitrate (p<0.01 for both);
      homovanillate, suberate, tartarate, 3-indoleacetate and 5-hydroxyindoleacetate
      (p<0.05 for all). These concentrations did not change significantly following LGG
      administration to the CMA patients, but a trend towards the control group was
      seen. Thus, CMA is associated with changes in some urinary organic acid levels.
      These differences between atopic infants with and without CMA could be
      investigated as a novel approach for CMA diagnosis.

PMID- 19397754
TI  - Time trends of co-existing atopic conditions in Singapore school children:
      prevalence and related factors.
AB  - Atopic diseases are known to co-exist and are interrelated. Their co-existence in
      a patient increases disease burden and morbidity. We sought to study the
      prevalence of co-existing atopic conditions over time and its associated risk
      factors among Singapore children. Data was collected from two respective The
      International Study of Asthma and Allergies in Childhood surveys conducted in
      1994 and 2001. Data on asthma, rhinitis and eczema were obtained from the
      responses to questions about wheezing, exercise-induced wheezing, nocturnal
      cough, rhinitis symptoms, rash, and diagnoses of asthma, rhinitis and eczema in
      the last 12 months. Data on demographic and known risk factors were also
      obtained. The prevalence of children who have had more than one atopic disorder
      increased significantly from 6.0% in 1994 to 10.2% in 2001 (p < 0.001). Parental
      history of atopic disease, maternal educational level, male gender and smoke
      exposure were significantly associated with co-existent atopic symptoms in the
      child. Among Singapore schoolchildren, there was a significant prevalence of co
      existent atopic disease and this prevalence was rising. The influences of both
      genetic and environmental factors were likely to have contributed to these
      observations.

PMID- 19397755
TI  - Maturation of cytokine-producing capacity from birth to 1 yr of age.
AB  - Little is known about the immunologic maturation in the early stages of life. The
      aim of this study was to investigate maturation of immune system from birth to 1
      yr of age and to compare immune functions between mothers and their children.
      Also the effect of atopy to the immune responses of children was examined. Cord
      blood samples (n = 228) and peripheral blood samples of children (n = 200) and
      their mothers (n = 208) 1 yr after birth were collected. Whole blood samples were
      stimulated for 24 and 48 h with Staphylococcal enterotoxin B (SEB),
      lipopolysaccharide (LPS) and the combination of phorbol ester and ionomycin
      (P/I). Production of TNF-alpha, IFN-gamma, IL-5, IL-8 and IL-10 was determined
      using ELISA. Significant mother-to-child correlation was detected in cytokine
      producing capacity at the age of 1 yr. TNF-alpha (P/I, SEB and LPS stimulation),
      IFN-gamma (P/I and SEB), IL-5 (P/I and SEB) and IL-10 (P/I, SEB and LPS)
      producing capacity increased from birth to 1 yr of age. In general, stimulated
      cytokine responses were higher in mothers' than in children's blood samples,
      except in the case of P/I and LPS-stimulated IL-8, which were highest at birth.
      Maternal inhalation atopy was associated with increased cord blood IL-5 (24 and
      48 h) and IL-10 (48 h) production following P/I stimulation. Also children of
      food atopic mothers expressed elevated cord blood IL-10 (48 h, P/I) responses and
      decreased IFN-gamma/IL-5 ratio (24 h, P/I). In addition, the production of IFN
      gamma (24 and 48 h, P/I) and the IFN-gamma/IL-5 ratio (24 h and 48 h, P/I) at the
      age of 1 yr was lower among children with food atopic mothers. In conclusion, our
      results suggest that both adaptive and innate immune responses increase from
      birth to 1 yr of age, but are still weak in comparison to adult responses.
      Cytokine responses of children begin to correlate with those of their mothers
      during the first year of life. Although only few associations were observed
      between atopy and cytokine-producing capacity, our results suggest that children
      of atopic mothers express T(h)2-polarized cytokine pattern.

PMID- 19397756
TI  - Increased rate and greater severity of allergic reactions to insect sting among
      schoolchildren with atopic diseases.
AB  - The question of whether atopic diseases are a risk factor for allergic reactions
      to insect sting is still unresolved. The aim of this study was to evaluate the
      association between atopic diseases (asthma, allergic rhinitis, atopic eczema)
      and allergic reactions to insect stings among schoolchildren in Israel. A self
      report questionnaire of the International Study of Asthma and Allergies in
      Childhood was administered to a national sample of 13-14-yr-old schoolchildren.
      Questions regarding reactions to insect stings were added. A total of 10,021
      questionnaires were available for analysis. Among the children who reported
      insect stings (56.3%), the prevalence of current asthma was 6.0%, of allergic
      rhinitis, 10.5%, and of atopic eczema, 8.7%, with no significant differences from
      the whole study population. Among children with any of the atopic diseases, 36.9%
      reported an allergic reaction to insect sting compared to 24.8% of the non-atopic
      children (p < 0.0001). On multivariate analysis, asthma, allergic rhinitis, and
      atopic eczema were found to be significant risk factors for allergic reactions of
      any severity. Children in the atopic group had a significantly higher rate of
      severe allergic reactions than the non-atopic children, and relatively higher
      rates of milder ones (p < 0.0001). Asthmatic patients with severe allergic
      reactions had more parameters of severe asthma than asthmatic patients with mild
      or no reactions. In conclusions, allergic diseases are associated with a higher
      rate and greater severity of allergic reactions to insect sting in children. The
      severity of the allergic reaction is related to the severity of the asthma
      symptoms.

PMID- 19397757
TI  - A splice site mutation is the cause of the high prevalence of oculocutaneous
      albinism type 2 in the Kuna population.

PMID- 19397758
TI  - Building the perfect beast: complex mouse models teach surprisingly simple
      melanoma lessons.

PMID- 19397759
TI  - Wild-type versus mutant MMP-8 in melanoma: 'when you come to a fork in the road,
      take it'.

PMID- 19397760
TI  - How did uncommon disorders become 'rare diseases'? History of a boundary object.
AB  - The category of 'rare diseases' has been in growing use in the fields of public
      health and patient advocacy for the past 15 years in Europe. In this socio
      historical inquiry, I argue that this category, which appeared initially as a by
      product of the orphan drug issue in the United States of America, is a boundary
      object. As such, it has different specific local uses: a meaningless category for
      physicians, it relates to the patients' experience of illness, whereas the
      pharmaceutical industry first considered it as being synonymous with small
      markets and then with innovation. Public bodies contributed to framing a common
      and blurred use, based on a statistical definition whose purpose was to foster co
      operation between the four groups involved in the issue. In the definition
      process of the category of rare diseases, the key actors were the patients and
      public bodies, not medical professionals or the pharmaceutical industry.

PMID- 19397761
TI  - Securitising health: Australian newspaper coverage of pandemic influenza.
AB  - This paper analyses contemporary Australian newspaper coverage of the threat of
      pandemic influenza in humans, specifically in the light of recent transformations
      in biomedical and public health understandings of infectious disease as
      continuously emerging. Our analysis suggests that the spectre of pandemic
      influenza is characterised, in newspaper accounts, as invoking a specific form of
      nation building. The Australian nation is depicted as successfully securing
      itself in the face of a threat from Asia (and in the absence of an effective
      international health body). What is described in newspaper accounts reflects a
      shift in the public health response to infectious disease. This response does not
      entail a direct focus on protecting either the population or national territory.
      Instead, it involves the continuous rehearsal of readiness to react to disasters
      through the networking of government and private agencies responsible for
      maintaining critical infrastructure. In this way, coverage of pandemic influenza
      positions health as central to national security, with little reporting of the
      reasons for or the potential implications of this alliance. Thus, the imperative
      to 'be prepared' is presented as self-evident.

PMID- 19397762
TI  - Understanding the social patterning of smoking practices: a dynamic typology.
AB  - In many countries, cigarette consumption has been on a declining trend for over
      20 years. However, different patterns of smoking practices have emerged. Our goal
      is to explore how the patterning of smoking practices occurs and persists over
      time, and to investigate the factors that could help interpret these patterns.
      Data were derived from the National Population Health Surveys and comprise a
      large representative sample of the population. Dynamic Typology methods reveal
      two main classes of typology: monothetic groups with stable patterns of behaviour
      over time (never-smokers, chronically addicted smokers, long-term ex-smokers);
      and polythetic groups with substantial behavioural variations. Moreover,
      socioeconomic inequalities are found among all groups, and gender-specific
      clusters of behaviour become apparent, with specific risk groups, such as the
      group of young women aged 20-24 at risk of becoming highly addicted. Our results
      also show that the effects of socioeconomic position on smoking practices are not
      significantly mediated by psychosocial variables such as self-esteem and personal
      control in both females and males. However, these variables still exert
      independent and differential effects on smoking practices in both genders. Our
      findings indicate that analysis of temporal patterns of smoking is crucial for
      tailoring type and timing of health-promoting interventions.

PMID- 19397763
TI  - Eugenic utopias/dystopias, reprogenetics, and community genetics.
AB  - The impetus for this review is the intriguing realisation that eugenics, viewed
      as dystopian and authoritarian in most of the 20th century, is in the process of
      being reinterpreted today--in the context of reproductive genetics--as utopian
      and liberal. This review offers an analytical framework for mapping the growing
      literature on this subject in order to provide a summary for both teaching and
      research in medical sociology. Recent works are subsumed and explored in three
      areas: historical criticism of the 'old eugenics'; the continuation of this
      stream in the form of criticism of reprogenetics as a new, 'backdoor' eugenic
      regime of bio-governmentality--an area which also includes the application of
      Foucauldian and feminist perspectives; and the recent enthusiasm regarding
      'liberal eugenics,' claiming that reprogenetic decisions should be left to
      individual consumers thus enhancing their options in the health market. The
      review concludes by discussing and illustrating potential research directions in
      this field, with a focus on the social and ethical aspects of 'community
      genetics' and its emerging networks of individuals genetically at risk.

PMID- 19397771
TI  - Comparison between lithium dilution and pulse contour analysis techniques for
      cardiac output measurement in isoflurane anaesthetized ponies: influence of
      different inotropic drugs.
AB  - OBJECTIVE: To compare cardiac output () measurements using lithium dilution
      (LiDCO) and pulse contour analysis (PulseCO) techniques in isoflurane
      anaesthetized ponies before and during the administration of different
      inotropic/vasoactive drugs. STUDY DESIGN: Prospective randomized experimental
      cross-over trial. ANIMALS: Six ponies aged 5.0 +/- 1.6 (4-6.5) years and weighing
      286 +/- 53 (212-368) kg. METHODS: After sedation (romifidine) and induction
      (midazolam + ketamine), anaesthesia was maintained with isoflurane in oxygen.
      After 90 minutes (= T0), one of four treatments was administered: saline 0.1 mL
      kg(-1) (S), enoximone 0.5 mg kg(-1) IV (E), enoximone followed by dobutamine (0.5
      microg kg(-1) minute(-1) for 120 minutes) (ED) or enoximone followed by a calcium
      chloride infusion (0.5 mg kg(-1) minute(-1) for 10 minutes) (EC). Data were
      recorded for 120 minutes after T0. The PulseCO (recorded from carotid artery) was
      calibrated before T0, no further recalibrations were performed. was determined
      with LiDCO ((LiDCO)) and PulseCO ((PulseCO)) simultaneously at T5, T10, T20, T40,
      T60, T80, T100 and T120. Systemic vascular resistances (SVR(LiDCO) and
      SVR(PulseCO)) were calculated. RESULTS: In the saline group, (PulseCO) was 4.9 +/
      12.3% lower than LiDCO (p < 0.01), whereas SVR(PulseCO) was 6.9 +/- 14.4% higher
      than SVR(LiDCO) (p < 0.01). These differences increased over time (mean +/- SEM),
      by 0.06 +/- 0.03% minute(-1) (p = 0.042) and SVR by 0.08 +/- 0.03% minute(-1) (p
      = 0.018). (PulseCO) was higher than (LiDCO) in the EC group (1.8 +/- 23.3%), but
      lower than (LiDCO) in groups E (-11.7 +/- 20.4%) and ED (-10.0 +/- 25.9%)
      (significant difference between treatments, p < 0.01). The differences in SVR in
      groups E (20.4 +/- 32.0%) and ED (20.7 +/- 35.3%) were significantly higher than
      in groups S (6.9 +/- 14.4%) and EC (3.1 +/- 22.2%) (p < 0.01). CONCLUSIONS AND
      CLINICAL RELEVANCE: Pulse contour analysis values deviated significantly from
      LiDCO measurements in isoflurane-anaesthetized ponies. This difference was
      influenced by inotropic/vasoactive drugs.

PMID- 19397772
TI  - In vitro validation of a Pitot-based flow meter for the measurement of
      respiratory volume and flow in large animal anaesthesia.
AB  - OBJECTIVE: To remodel and validate commercially available monitors and their
      Pitot tube-based flow sensors for use in large animals, using in vitro
      techniques. STUDY DESIGN: Prospective, in vitro experiment. METHODS: Both the
      original and the remodelled sensor were studied with a reference flow generator.
      Measurements were taken of the static flow-pressure relationship and linearity of
      the flow signal. Sensor airway resistance was calculated. Following recalibration
      of the host monitor, volumes ranging from 1 to 7 L were generated by a
      calibration syringe, and bias and precision of spirometric volume was determined.
      Where manual recalibration was not available, a conversion factor for volume
      measurement was determined. The influence of gas composition mixture and peak
      flow on the conversion factor was studied. RESULTS: Both the original and the
      remodelled sensor showed similar static flow-pressure relationships and linearity
      of the flow signal. Mean bias (%) of displayed values compared with the reference
      volume of 3, 5 and 7 L varied between -0.4% and +2.4%, and this was significantly
      smaller than that for 1 L (4.8% to +5.0%). Conversion factors for 3, 5 and 7 L
      were very similar (mean 6.00 +/- 0.2, range 5.91-6.06) and were not significantly
      influenced by the gas mixture used. Increasing peak flow caused a small decrease
      in the conversion factor. Volume measurement error and conversion factors for
      inspiration and expiration were close to identity. CONCLUSION: The combination of
      the host monitor with the remodelled flow sensor allowed accurate in vitro
      measurement of flows and volumes in a range expected during large animal
      anaesthesia. CLINICAL RELEVANCE: This combination has potential as a reliable
      spirometric monitor for use during large animal anaesthesia.

PMID- 19397773
TI  - A comparison of the duration and quality of recovery from isoflurane, sevoflurane
      and desflurane anaesthesia in dogs undergoing magnetic resonance imaging.
AB  - OBJECTIVE: To compare the recovery after anaesthesia with isoflurane, sevoflurane
      and desflurane in dogs undergoing magnetic resonance imaging (MRI) of the brain.
      STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: Thirty-eight dogs
      weighing 23.7 +/- 12.6 kg. METHODS: Following pre-medication with meperidine, 3
      mg kg(-1) administered intramuscularly, anaesthesia was induced intravenously
      with propofol (mean dose 4.26 +/- 1.3 mg kg(-1)), the trachea was intubated, and
      an inhalational anaesthetic agent was administered in oxygen. The dogs were
      randomly allocated to one of three groups: group I (n = 13) received isoflurane,
      group S (n = 12) received sevoflurane and group D (n = 13) received desflurane.
      Parameters recorded included cardiopulmonary data, body temperature, end-tidal
      anaesthetic concentration, duration of anaesthesia, and recovery times and
      quality. Qualitative data were compared using chi-squared and Fisher's exact
      tests and quantitative data with anova and Kruskal-Wallis test. Post-hoc
      comparisons for quantitative data were undertaken with the Mann-Whitney U-test.
      RESULTS: The duration of anaesthesia [mean and standard deviation (SD)] in group
      I was: 105.3 (27.48) minutes, group S: 120.67 (19.4) minutes, and group D: 113.69
      (26.68) minutes (p = 0.32). Times to extubation [group I: 8 minutes,
      (interquartile range 6-9.5), group S: 7 minutes (IQR 5-7), group D: 5 minutes
      (IQR 3.5-7), p = 0.017] and to sternal recumbency [group I: 11 minutes (IQR 9.5
      13.5), group S: 9.5 minutes (IQR 7.25-11.75), group D: 7 minutes (range 3.5
      11.5), p = 0.048] were significantly different, as were times to standing. One
      dog, following sevoflurane, had an unacceptable quality of recovery, but most
      other recoveries were calm, with no significant difference between groups.
      CONCLUSIONS AND CLINICAL RELEVANCE: All three agents appeared suitable for use.
      Dogs' tracheas were extubated and the dogs recovered to sternal recumbency most
      rapidly after desflurane. This may be advantageous for animals with some
      neurological diseases and for day case procedures.

PMID- 19397774
TI  - Influence of two different ventilation modes on the function of an anaesthetic
      conserving device in sevoflurane anaesthetized piglets.
AB  - OBJECTIVE: To investigate the influence of two ventilation modes on the
      performance of an anaesthetic conserving device (AnaConDa) in piglets. STUDY
      DESIGN: Prospective randomized experimental trial. ANIMALS: Eight female piglets
      weighing 24.7 +/- 2.2 kg. METHODS: Anaesthesia was maintained with sevoflurane
      (in 60% oxygen) delivered from the AnaConDa placed between endotracheal tube
      (ETT) and Y-piece. Anaesthetic depth was guided using standard clinical
      parameters. Ventilation mode was volume controlled (VC) during the first and
      pressure support (PS) during the second period of anaesthesia in four piglets
      (group 1); the order was reversed in group 2. Anaesthetic gases were sampled
      before (at the proximal end of the ETT) and after the AnaConDa (Y-piece). Data
      were analysed using a model I anova, with treatment and group as fixed
      categorical effects. Using a paired t-test, partial pressures of carbon dioxide
      (Pe'CO(2)) on both sides of the device were compared. RESULTS: Although the mean
      administration rate of sevoflurane was comparable in both groups (3.8 +/- 1.8 mL
      hour(-1)), E'Sevo was higher in group 1, more specifically during the first
      period (p = 0.035). Less sevoflurane escaped during VC (14.0 +/- 3.4%) compared
      with PS ventilation (17.2 +/- 5.7%) (p = 0.001). Pe'CO(2) was lower at the Y
      piece (6.4 +/- 0.8 kPa, 48 +/- 6 mmHg) compared with the ETT (9.3 +/- 1.4 kPa, 70
      +/- 11 mmHg) in both groups and ventilation modes. On average, inspiratory CO(2)
      tension was 2.0 +/-1.0 kPa (15 +/- 8 mmHg). Respiration rate was comparable in
      all piglets while tidal volume () and peak inspiratory pressure were lower during
      VC compared with PS (p < 0.001, p = 0.015 respectively). CONCLUSIONS AND CLINICAL
      RELEVANCE: The observed differences in E'Sevo concentration and sevoflurane
      breakthrough were probably related to differences in . The observed high FiCO(2)
      indicated an excessive dead space with the AnaConDa for these piglets.

PMID- 19397775
TI  - Effects of propofol administration rates on cardiopulmonary function and
      anaesthetic depth during anaesthetic induction in rats.
AB  - OBJECTIVE: To compare the effect of three different administration rates of one
      dose of propofol on the depth and duration of anaesthesia and cardiopulmonary
      function during induction of anaesthesia in rats using electroencephalogram (EEG)
      and clinical signs. STUDY DESIGN: Prospective, randomized experimental trial.
      Animals Twenty-one, adult, male Sprague-Dawley rats weighing 341 +/- 26 g (mean
      +/- SD) (325 to 480 g). METHODS:  ANIMALS: were randomly divided into three
      groups to receive 20 mg kg(-1) propofol as a bolus injection over 1, 2 or 3
      minutes (groups P1, P2 and P3 respectively) intravenously (IV). The total
      duration and number of burst suppression (BS) episodes in the EEG, the time to
      loss of righting reflex, reflex score from electrical stimulation, respiratory
      rate, mean arterial pressure and pulse rate were measured from the beginning of
      propofol injection. RESULTS: While loss of reflex to electrical stimulus and time
      to loss of righting reflex in group P3 were slower than in other groups, the
      total duration and number of BS episodes in group P3 were significantly higher
      than in groups P1 and P2 and cardiopulmonary depression was less prominent in
      group P3 than in groups P1 and P2 up to 2 minutes after the start of
      administration. CONCLUSIONS: Twenty milligram per kg propofol administration IV
      for 3 minutes increased the duration of anaesthesia and decreased cardiopulmonary
      depression in rats. CLINICAL RELEVANCE: Slower infusion of propofol produced
      surgical anaesthesia with less cardiopulmonary depression in rats.

PMID- 19397776
TI  - The post-tetanic count during vecuronium-induced neuromuscular blockade in
      halothane-anaesthetized dogs.
AB  - OBJECTIVE: To evaluate the post-tetanic count (PTC) for predicting the return of
      reversible neuromuscular blockade at the n. facialis-m. nasolabialis (nF-mNL) and
      n. ulnaris-mm. carpi flexorii (nU-mCF) nerve-muscle units (NMUs) during profound
      vecuronium neuromuscular blockade in halothane-anaesthetized dogs. STUDY DESIGN:
      Randomized, prospective, experimental study. ANIMALS: Twenty-five dogs (seven
      male 18 female) undergoing surgery; mean age: 4.8 years; mean body weight 22 kg.
      METHODS: Thirty minutes after acepromazine (0.05 mg kg(-1)) and morphine (0.5 mg
      kg(-1)) pre-medication, anaesthesia was induced with intravenous (IV) thiopental
      and maintained with halothane, N(2)O and O(2). The lungs were mechanically
      ventilated and end-tidal halothane concentration (Fe'(HAL)) maintained at 1.04%.
      Neuromuscular transmission was monitored using the train-of-four count (TOFC) at
      one nF-mNL and both nU-mCF units. Vecuronium (50 microg kg(-1) IV) was injected
      after 15 minutes constant Fe'(HAL). When the first twitch (T1) at both nU-mCF
      units had disappeared (t = 0) one (randomly allocated) ulnar nerve was stimulated
      every 5 minutes using PTC; TOF stimulation continued at the other sites. The PTC
      was plotted against the interval between recording time and T1's reappearance at
      the other NMUs. RESULTS: At t = 0, the mean PTC in the contralateral nU-mCF unit
      was 18 (range 0-20). Mean PTC was a minimum at t = 5, rising to the maximum (20)
      at 25 minutes. Six dogs were vecuronium-resistant as monitored by PTC. Excluding
      data from these revealed a strong negative relationship between ulnar PTC and the
      time taken for T1's return at the facial (r = -0.7018; p < 0.00001) and
      contralateral ulnar (r = -0.8409; p < 0.00001) NMUs. CONCLUSION AND CLINICAL
      RELEVANCE: Post-tetanic count monitoring beginning >5 minutes after the TOFC at
      nU-mCF = 0 provided a reliable estimate of T1's return at ulnar and facial NMUs.

PMID- 19397777
TI  - Metabolic changes associated with anaesthesia and cherry poisoning in a pony.
AB  - OBSERVATIONS: A case of a pony with severe cyanide intoxication as a result of
      cherry ingestion is presented. General anaesthesia was performed for colic
      surgery. Severe metabolic lactate acidosis in combination with a high arterial
      oxygen partial pressure and clinically good peripheral perfusion parameters were
      the remarkable signs during anaesthesia. Severe hypothermia was obvious during
      recovery. Ten hours post-surgery the pony was euthanized as a result of
      neurological signs. The diagnosis of cyanide intoxication was made post-mortem.
      CONCLUSION: Cherry ingestion can lead to lethal cyanide intoxication in horses
      indicated by severe nonhypoxic lactic acidosis during anaesthesia.

PMID- 19397778
TI  - Modulation of nociceptive withdrawal reflexes evoked by single and repeated
      nociceptive stimuli in conscious dogs by low-dose acepromazine.
AB  - OBJECTIVES: To investigate the modulation of the nociceptive withdrawal reflex
      (NWR) and temporal summation (TS) by low-dose acepromazine (ACP) in conscious
      dogs. To assess the short- and long-term stability of the reflex thresholds.
      STUDY DESIGN: Randomized, blinded, placebo-controlled cross-over experimental
      study. ANIMALS: Eight adult male Beagles. METHODS: The NWR was elicited using
      single transcutaneous electrical stimulation of the ulnar nerve. Repeated stimuli
      (10 pulses, 5 Hz) were applied to evoke TS. The responses of the deltoideus
      muscle were recorded and quantified by surface electromyography and the
      behavioural reactions were scored. Each dog received 0.01 mg kg(-1) ACP or an
      equal volume saline intravenously (IV) at 1 week intervals. Measurements were
      performed before (baseline) and 20, 60 and 100 minutes after drug administration.
      Sedation was scored before drug administration and then at 10 minutes intervals.
      Data were analyzed with Friedman repeated measures analysis of variance on ranks
      and Wilcoxon signed rank tests. RESULTS: Acepromazine resulted in a mild
      tranquilization becoming obvious at 20 minutes and peaking 30 minutes after
      injection. Single (I(t)) and repeated stimuli (TS(t)) threshold intensities, NWR
      and TS characteristics and behavioural responses were not affected by the ACP at
      any time point. Both I(t) and TS(t) were stable over time. CONCLUSIONS AND
      CLINICAL RELEVANCE: In dogs, 0.01 mg kg(-1) ACP IV had no modulatory action on
      the NWR evoked by single or repeated stimuli, suggesting no antinociceptive
      activity on phasic nociceptive stimuli. The evidence of the stability of the NWR
      thresholds supports the use of the model as an objective tool to investigate
      nociception in conscious dogs. A low dose of ACP administered as the sole drug,
      can be used to facilitate the recordings in anxious subjects without altering the
      validity of this model.

PMID- 19397779
TI  - Effects of age on the electroencephalographic response to castration in lambs
      anaesthetized with halothane in oxygen from birth to 6 weeks old.
AB  - OBJECTIVES: To characterize changes in the cerebro-cortical response of lambs to
      rubber-ring castration during the first 6 weeks of postnatal life. ANIMALS:
      Coopworth-Texel cross ram lambs between 3 hours and 44 days of age. METHODS: The
      electroencephalogram (EEG) and heart rate responses to rubber ring castration
      were compared. Anaesthesia was induced via a face mask and maintained with
      halothane in oxygen (e'(Hal) = 1.2%). Once a stable plane of anaesthesia had been
      achieved, data collection of EEG and electrocardiogram (ECG) commenced, and the
      lambs were castrated 15 minutes later, using rubber rings. Heart rate was derived
      from the ECG and the median frequency (F(50)), spectral edge frequency (F(95))
      and total power (p(tot)) were derived from the EEG. RESULTS: Castration-induced
      changes in F(50) increased from 2 +/- 1.8% in the youngest lambs to a maximum of
      33 +/- 8.9% in the 36 +/- 0.5 day-old lambs. Changes in F(95) increased from -7
      +/- 3% in the youngest lambs to a maximum of 16 +/- 11% in the 36 +/- 0.5 day-old
      lambs. Linear regression analysis in lambs up to 10 days of age demonstrated a
      change in the response with age that was significantly different from zero for
      F(50) (r(2) = 0.28, p = 0.007) and F(95) (r(2) = 0.38, p = 0.001), but not for
      p(tot) or heart rate. CONCLUSION: This study identified significant changes in
      the responsiveness of the lambs' cerebral cortex to the noxious stimulation of
      castration over the first 7-10 days of postnatal life. The results suggest that
      mechanisms that suppress responses of the fetus to noxious stimulation may still
      be active in the first few days after birth. CLINICAL RELEVANCE: This study
      documents changes in central nociceptive processing which may reflect the ability
      of neonatal animals to perceive pain.

PMID- 19397780
TI  - Effects of intraarticular ropivacaine and morphine on lipopolysaccharide-induced
      synovitis in horses.
AB  - OBJECTIVE: To compare the intraarticular (IA) analgesic effects of ropivacaine
      and morphine in horses with experimentally induced synovitis. STUDY DESIGN:
      Randomized, blinded cross-over design. ANIMALS: Twelve healthy mixed breed horses
      between 8-15 years old. METHODS: Synovitis was induced in the left radio-carpal
      joint with an injection of lipopolysaccharide (Escherichia coli 055:B5). Six
      hours later, the horses were treated with an IA injection of 40 mg of ropivacaine
      (ROPI), 40 mg of morphine (MOR), 20 mg of ropivacaine added to 20 mg of morphine
      in saline (RM) or 4 mL of saline (SAL), as control. Analgesia was measured
      subjectively using a numerical rating scale, a simple descriptive scale, pain
      upon maximal flexion of the carpus and by the range of motion exhibited by the
      affected joint. Data are reported as mean +/- SD and were analyzed using anova.
      Blood and synovial data were analyzed by split plots in time with units
      (treatments: SAL, ROPI, MOR and RM) and subunits (times: T0-24), in a completely
      randomized design with six replicates. Mean comparisons were made by Tukey's
      test; differences were considered significant at p < 0.05. RESULTS: Ropivacaine
      had a clinical analgesic effect with a relative short duration ( approximately
      2.5 to 3.5 hours). Morphine had a slower onset of action than ROPI, but a
      stronger analgesic effect of longer duration. The RM showed an earlier onset of
      action than MOR and had a strong analgesic effect for the 24-hour post-injection
      period. All treatments caused a significant decrease in total nucleated cells
      compared with the control, 24 hours after administration. CONCLUSIONS AND
      CLINICAL RELEVANCE: Morphine alone or in combination with ropivacaine produced a
      strong analgesic effect of prolonged duration, which may offer pain relief for
      acute synovitis for at least 24 hours.

PMID- 19397781
TI  - Integrin alpha1beta1 is involved in the differentiation into myofibroblasts in
      adult reactive tissues in vivo.
AB  - Connective tissue cell activation is of importance during reactive conditions
      such as solid tumour growth, wound healing and pannus formation in rheumatoid
      arthritis. Here, we have compared connective tissue cells of mesenchymal origin
      in human tissues from these conditions and their normal counterparts using a
      panel of cell-type-specific markers. In particular, we investigated variations of
      integrin expression among connective tissue cell phenotypes. Connective tissue
      cell populations were defined based on their association with the
      microvasculature and their expression of activation markers. The phenotype of
      these cells varied according to the type of pathological connective tissue
      examined. Our morphological data from human tissues suggested that the
      alpha(1)beta(1) integrin, a collagen/laminin receptor, is involved in the
      differentiation of precursor cells into myofibroblasts. To mechanistically
      investigate this hypothesis, we employed experimental models for carcinoma growth
      and wound healing utilizing alpha(1) integrin-deficient mice. The data confirmed
      that the alpha(1)beta(1) integrin is of importance not only for the
      differentiation of mesenchymal cells into myofibroblasts but also for the
      neovascularization and connective tissue organization and emphasize the
      importance of myofibroblasts in the pathophysiology of tissue repair,
      inflammation and tumour growth.

PMID- 19397782
TI  - MMPs/TIMPs and inflammatory signalling de-regulation in human incisional hernia
      tissues.
AB  - BACKGROUND: Incisional hernia is a common and important complication of
      laparotomies. Epidemiological studies allude to an underlying biological cause,
      at least in a subset of population. Interest has mainly focused on abnormal
      collagen metabolism. However, the role played by other determinants of
      extracellular matrix (ECM) composition is unknown. To date, there are few
      laboratory studies investigating the importance of biological factors
      contributing to incisional hernia development. We performed a descriptive tissue
      based analysis to elucidate the possible relevance of matrix metalloproteinases
      (MMPs) and their tissue inhibitors (TIMPs) in association with local cytokine
      induction in human incisional hernia tissues. The expression profiles of MMPs,
      TIMPs and pro-inflammatory cytokine signalling were investigated in aponeurosis
      and skeletal muscle specimens taken intraoperatively from incisional hernia (n=
      10) and control (n= 10) patients. Semiquantitative RT-PCR, zymography and
      immunoblotting analyses were done. Incisional hernia samples displayed
      alterations in the microstructure and loss of ECM, as assessed by histological
      analyses. Moreover, incisional hernia tissues showed increased MMP/TIMP ratios
      and de-regulated inflammatory signalling (tumor necrosis factor [TNFA] and
      interleukin [IL]-6 tended to increase, whereas aponeurosis TNFA receptors
      decreased). The changes were tissue-specific and were detectable at the mRNA
      and/or protein level. Statistical analyses showed several associations between
      individual MMPs, TIMPs, interstitial collagens and inflammatory markers. The
      increment of MMPs in the absence of a counterbalance by TIMPs, together with an
      ongoing de-regulated inflammatory signalling, may contribute in inducing a
      functional defect of the ECM network by post-translational mechanisms, which may
      trigger abdominal wall tissue loss and eventual rupture. The notable TIMP3
      protein down-regulation in incisional hernia fascia may be of pathophysiological
      significance. We conclude that this study may help to pinpoint novel hypotheses
      of pathogenesis that can lead to a better understanding of the disease and
      ultimately to improvement in current therapeutic approaches.

PMID- 19397783
TI  - VEGF is a mediator of the renoprotective effects of multipotent marrow stromal
      cells in acute kidney injury.
AB  - Adult stem cell treatment of complex disorders is a promising therapeutic
      approach and multipotent marrow stromal cells (MSCs) have been shown to be
      effective in various animal models of diseases. Acute kidney injury (AKI) is a
      common and serious problem in hospitalized patients and bone marrow derived
      multipotent MSCs have been shown to be effective in different models of AKI. The
      mechanism of action of MSCs is complex but involves paracrine actions including
      growth factor secretion. Knockdown of vascular enthothelial growth factor (VEGF)
      by siRNA reduced effectiveness of MSCs in the treatment of ischemic AKI in a rat
      model. Animals treated with MSCs had increased renal microvessel density compared
      to VEGF knockdown MSC-treated and vehicle-treated animals. These results show
      that VEGF is an important mediator of the early and late phase of renoprotective
      action after AKI in the context of stem cell treatment.

PMID- 19397784
TI  - Splenic natural killer cell activity in two models of experimental
      neurodegenerative diseases.
AB  - Natural killer (NK) cells are antitumour/anti-viral effectors and play important
      roles in shaping the immune system, but their role in neurodegenerative diseases
      is not clear. Here, we investigated the fate of these cells in two
      neurodegenerative diseases. In the first model, the activity of NK cells was
      examined in mice with experimental autoimmune encephalomyelitis (EAE) treated
      with glatiramer acetate (GA or Copaxone), a drug used to treat EAE in animals and
      multiple sclerosis in human. The second disease model is twitcher
      (Galc(twi)/Galc(twi)) mice, which represents an authentic model of human Krabbe's
      disease. Administration of GA ameliorated EAE in SJL mice corroborated with
      isolating NK cells that expressed higher killing than cells isolated from vehicle
      dosed animals against immature or mature dendritic cells (DCs). However, this
      drug showed no effect on the numbers of NK cells or the expression of CD69
      molecule. On the other hand, NK cells either disappeared from the spleens or were
      present in low numbers in the white pulp areas of Galc(twi)/Galc(twi) mice, which
      have increased D-galactosyl-beta1-1'-sphingosine (GalSph) levels. Analysis by
      confocal microscopy shows that NK cells found in the spleens of
      Galc(twi)/Galc(twi) mice were apoptotic. Incubating NK cells in vitro with GalSph
      induced the apoptosis in these cells, confirming the results of twitcher mice.
      Our results provide the first evidence showing that amelioration of EAE in mice
      is corroborated with NK cell lysis of antigen-presenting DCs, whereas NK cell
      distribution into the spleen is altered in a devastating lipid disorder
      corroborated with induction of their apoptosis.

PMID- 19397785
TI  - Laminin isoforms in human embryonic stem cells: synthesis, receptor usage and
      growth support.
AB  - To reveal the functional intrinsic niche of human embryonic stem cells (hESC) we
      examined the production of basement membrane (BM) proteins and the presence of
      their receptors in feeder-free cell culture conditions. In addition, we
      investigated binding of hESCs to purified human BM proteins and identified the
      receptors mediating these contacts. Also, we tested whether purified human
      laminin (Lm) isoforms have a role in hESC self-renewal and growth in short-term
      cultures. The results show that hESCs synthesize Lm alpha(1) and Lm alpha(5)
      chains together with Lm beta(1) and gamma(1) chains suggesting the production of
      Lms-111 and -511 into the culture medium and deposits on cells. hESCs contain
      functionally important integrin (Int) subunits, Int beta(1), alpha(3), alpha(6),
      alpha(5), beta(5) and alpha(V), as well as the Lm alpha(5) receptor, Lutheran
      (Lu) glycoprotein and its truncated form, basal cell adhesion molecule (B-CAM).
      In cell adhesion experiments, Int beta(1) was crucial for adhesion to most of the
      purified human BM proteins. Lu/B-CAM mediated adhesion to Lm-511 together with
      Int alpha(3)beta(1), and was essential for the adhesion of hESCs to embryonic
      feeder cells. Adhesion to Lm-411 was mediated by Int alpha(6)beta(1). Lm-511
      supported hESC growth in defined medium equally well as Matrigel. These results
      provide consequential information of the biological role of BM in hESCs,
      warranting further investigation of BM biology of human pluripotent stem cells.

PMID- 19397786
TI  - The calcium-sensing receptor regulates parathyroid hormone gene expression in
      transfected HEK293 cells.
AB  - BACKGROUND: The parathyroid calcium receptor determines parathyroid hormone
      secretion and the response of parathyroid hormone gene expression to serum Ca2+
      in the parathyroid gland. Serum Ca2+ regulates parathyroid hormone gene
      expression in vivo post-transcriptionally affecting parathyroid hormone mRNA
      stability through the interaction of trans-acting proteins to a defined cis
      element in the parathyroid hormone mRNA 3'-untranslated region. These parathyroid
      hormone mRNA binding proteins include AUF1 which stabilizes and KSRP which
      destabilizes the parathyroid hormone mRNA. There is no parathyroid cell line;
      therefore, we developed a parathyroid engineered cell using expression vectors
      for the full-length human parathyroid hormone gene and the human calcium
      receptor. RESULTS: Co-transfection of the human calcium receptor and the human
      parathyroid hormone plasmid into HEK293 cells decreased parathyroid hormone mRNA
      levels and secreted parathyroid hormone compared with cells that do not express
      the calcium receptor. The decreased parathyroid hormone mRNA correlated with
      decreased parathyroid hormone mRNA stability in vitro, which was dependent upon
      the 3'-UTR cis element. Moreover, parathyroid hormone gene expression was
      regulated by Ca2+ and the calcimimetic R568, in cells co-transfected with the
      calcium receptor but not in cells without the calcium receptor. RNA
      immunoprecipitation analysis in calcium receptor-transfected cells showed
      increased KSRP-parathyroid hormone mRNA binding and decreased binding to AUF1.
      The calcium receptor led to post-translational modifications in AUF1 as occurs in
      the parathyroid in vivo after activation of the calcium receptor. CONCLUSION: The
      expression of the calcium receptor is sufficient to confer the regulation of
      parathyroid hormone gene expression to these heterologous cells. The calcium
      receptor decreases parathyroid hormone gene expression in these engineered cells
      through the parathyroid hormone mRNA 3'-UTR cis element and the balanced
      interactions of the trans-acting factors KSRP and AUF1 with parathyroid hormone
      mRNA, as in vivo in the parathyroid. This is the first demonstration that the
      calcium receptor can regulate parathyroid hormone gene expression in heterologous
      cells.

PMID- 19397787
TI  - Lactobacillus delbrueckii ssp. bulgaricus B-30892 can inhibit cytotoxic effects
      and adhesion of pathogenic Clostridium difficile to Caco-2 cells.
AB  - BACKGROUND: Probiotic microorganisms are receiving increasing interest for use in
      the prevention, treatment, or dietary management of certain diseases, including
      antibiotic-associated diarrhea (AAD). Clostridium difficile is the most common
      cause of AAD and the resulting C. difficile - mediated infection (CDI), is
      potentially deadly. C. difficile associated diarrhea (CDAD) is manifested by
      severe inflammation and colitis, mostly due to the release of two exotoxins by C.
      difficile causing destruction of epithelial cells in the intestine. The aim of
      this study was to determine the effect of probiotic bacteria Lactobacillus
      delbrueckii ssp. bulgaricus B-30892 (LDB B-30892) on C. difficile-mediated
      cytotoxicity using Caco-2 cells as a model. METHODS: Experiments were carried out
      to test if the cytotoxicity induced by C. difficile-conditioned-medium on Caco-2
      cells can be altered by cell-free supernatant (CFS) from LDB B-30892 in different
      dilutions (1:2 to 1:2048). In a similar experimental setup, comparative
      evaluations of other probiotic strains were made by contrasting the results from
      these strains with the results from LDB B-30892, specifically the ability to
      affect C. difficile induced cytotoxicity on Caco-2 monolayers. Adhesion assays
      followed by quantitative analysis by Giemsa staining were conducted to test if
      the CFSs from LDB B-30892 and other probiotic test strains have the capability to
      alter the adhesion of C. difficile to the Caco-2 monolayer. Experiments were also
      performed to evaluate if LDB B-30892 or its released components have any
      bactericidal effect on C. difficile. RESULTS AND DISCUSSION: Co-culturing of LDB
      B-30892 with C. difficile inhibited the C. difficile-mediated cytotoxicity on
      Caco-2 cells. When CFS from LDB B-30892-C. difficile co-culture was administered
      (up to a dilution of 1:16) on Caco-2 monolayer, there were no signs of
      cytotoxicity. When CFS from separately grown LDB B-30892 was mixed with the cell
      free toxin preparation (CFT) of separately cultured C. difficile, the LDB B-30892
      CFS was inhibitory to C. difficile CFT-mediated cytotoxicity at a ratio of 1:8
      (LDB B-30892 CFS:C. difficile CFT). We failed to find any similar inhibition of
      C. difficile-mediated cytotoxicity when other probiotic organisms were tested in
      parallel to LDB B-30892. Our data of cytotoxicity experiments suggest that LDB B
      30892 releases one or more bioactive component(s) into the CFS, which neutralizes
      the cytotoxicity induced by C. difficile, probably by inactivating its toxin(s).
      Our data also indicate that CFS from LDB B-30892 reduced the adhesion of C.
      difficile by 81%, which is significantly (P <0.01) higher than all other
      probiotic organisms tested in this study. CONCLUSION: This study reveals the very
      first findings that Lactobacillus delbrueckii ssp. bulgaricus B-30892 (LDB B
      30892) can eliminate C. difficile-mediated cytotoxicity, using Caco-2 cells as a
      model. The study also demonstrates that LDB B-30892 can reduce the colonization
      of C. difficile cells in colorectal cells. More study is warranted to elucidate
      the specific mechanism of action of such reduction of cytotoxicity and
      colonization.

PMID- 19397788
TI  - Ankle-brachial index in HIV infection.
AB  - Prognosis for patients with the human immunodeficiency virus (HIV) has improved
      with the introduction of highly active antiretroviral therapy (HAART). Evidence
      over recent years suggests that the incidence of cardiovascular disease is
      increasing in HIV patients. The ankle-brachial index (ABI) is a cheap and easy
      test that has been validated in the general population. Abnormal ABI values are
      associated with increased cardiovascular mortality. To date, six series of ABI
      values in persons with HIV have been published, but none was a prospective study.
      No agreement exists concerning the risk factors for an abnormal ABI, though its
      prevalence is clearly higher in these patients than in the general population.
      Whether this higher prevalence of an abnormal ABI is associated with a higher
      incidence of vascular events remains to be determined.

PMID- 19397789
TI  - Marker-free image registration of electron tomography tilt-series.
AB  - BACKGROUND: Tilt series are commonly used in electron tomography as a means of
      collecting three-dimensional information from two-dimensional projections. A
      common problem encountered is the projection alignment prior to 3D
      reconstruction. Current alignment techniques usually employ gold particles or
      image derived markers to correctly align the images. When these markers are not
      present, correlation between adjacent views is used to align them. However,
      sequential pairwise correlation is prone to bias and the resulting alignment is
      not always optimal. RESULTS: In this paper we introduce an algorithm to find
      regions of the tilt series which can be tracked within a subseries of the tilt
      series. These regions act as landmarks allowing the determination of the
      alignment parameters. We show our results with synthetic data as well as
      experimental cryo electron tomography. CONCLUSION: Our algorithm is able to
      correctly align a single-tilt tomographic series without the help of fiducial
      markers thanks to the detection of thousands of small image patches that can be
      tracked over a short number of images in the series.

PMID- 19397790
TI  - Propofol: neuroprotection in an in vitro model of traumatic brain injury.
AB  - INTRODUCTION: The anaesthetic agent propofol (2,6-diisopropylphenol) has been
      shown to be an effective neuroprotective agent in different in vitro models of
      brain injury induced by oxygen and glucose deprivation. We examined its
      neuroprotective properties in an in vitro model of traumatic brain injury.
      METHODS: In this controlled laboratory study organotypic hippocampal brain-slice
      cultures were gained from six- to eight-day-old mice pups. After 14 days in
      culture, hippocampal brain slices were subjected to a focal mechanical trauma and
      subsequently treated with different molar concentrations of propofol under both
      normo- and hypothermic conditions. After 72 hours of incubation, tissue injury
      assessment was performed using propidium iodide (PI), a staining agent that
      becomes fluorescent only when it enters damaged cells via perforated cell
      membranes. Inside the cell, PI forms a fluorescent complex with nuclear DNA.
      RESULTS: A dose-dependent reduction of both total and secondary tissue injury
      could be observed in the presence of propofol under both normo- and hypothermic
      conditions. This effect was further amplified when the slices were incubated at
      32 degrees C after trauma. CONCLUSIONS: When used in combination, the dose
      dependent neuroprotective effect of propofol is additive to the neuroprotective
      effect of hypothermia in an in vitro model of traumatic brain injury.

PMID- 19397792
TI  - Decytabine enhances cytotoxicity induced by oxaliplatin and 5-fluorouracil in the
      colorectal cancer cell line Colo-205.
AB  - BACKGROUND: DNA methylation is an epigenetic phenomenon known to play an
      important role in the development of cancers, including colorectal cancer (CRC).
      Aberrant methylation of promoter regions of genes is potentially reversible, and
      if methylation is important for cancer survival, demethylation should do the
      opposite. To test this we have addressed the hypothesis that DNA
      methyltransferase inhibitors (DNMTi), decytabine and zebularine, potentiate
      inhibitory effects of classical anti-CRC cytostatics, oxaliplatin and 5
      fluorouracil (5-FU), on survival of CRC cells in vitro. RESULTS: Isobole and
      median effect analysis revealed that decytabine shows potent synergistic
      interaction with oxaliplatin and 5-FU and that this is probably not the class
      effect of DNMTi as zebularine shows strong antagonistic interaction with
      oxaliplatin. The synergistic combination treatment was also applied to the
      cultures to investigate their mechanisms of action. We have shown that
      combinations of decytabine with cytostatics produced dose-dependent growth
      inhibition and treatment-induced apoptosis. CONCLUSION: The observed synergism
      between decytabine and cytostatics is most probably related to the augmented
      apoptotic signal and allowed for significant (both biologically and
      statistically) reduction of the cytotoxic doses of cytostatics used.

PMID- 19397791
TI  - Identification of genes differentially expressed in dorsal and ventral chick
      midbrain during early development.
AB  - BACKGROUND: During the development of the central nervous system (CNS),
      patterning processes along the dorsoventral (DV) axis of the neural tube generate
      different neuronal subtypes. As development progresses these neurons are arranged
      into functional units with varying cytoarchitecture, such as laminae or nuclei
      for efficient relaying of information. Early in development ventral and dorsal
      regions are similar in size and structure. Different proliferation rates and cell
      migration patterns are likely to result in the formation of laminae or nuclei,
      eventually. However, the underlying molecular mechanisms that establish these
      different structural arrangements are not well understood.We undertook a
      differential display polymerase chain reaction (DD-PCR) screen to identify genes
      with distinct expression patterns between dorsal and ventral regions of the chick
      midbrain in order to identify genes which regulate the sculpturing of such
      divergent neuronal organisation. We focused on the DV axis of the early chick
      midbrain since mesencephalic alar plate and basal plate develop into laminae and
      nuclei, respectively. RESULTS: We identified 53 differentially expressed bands in
      our initial screen. Twenty-six of these could be assigned to specific genes and
      we could unambiguously show the differential expression of five of the isolated
      cDNAs in vivo by in situ mRNA expression analysis. Additionally, we verified
      differential levels of expression of a selected number of genes by using reverse
      transcriptase (RT) PCR method with gene-specific primers.One of these genes, QR1,
      has been previously cloned and we present here a detailed study of its early
      developmental time course and pattern of expression providing some insights into
      its possible function. Our phylogenetic analysis of QR1 shows that it is the
      chick orthologue of Sparc-like 1/Hevin/Mast9 gene in mice, rats, dogs and humans,
      a protein involved in cell adhesion. CONCLUSION: This study reveals some possible
      networks, which might be involved in directing the difference in neuronal
      specification and cytoarchitecture observed in the brain.

PMID- 19397793
TI  - Short hairpin-loop-structured oligodeoxynucleotides reduce HSV-1 replication.
AB  - The Herpes simplex virus (HSV) is known as an infectious agent and widespread in
      the human population. The symptoms of HSV infections can range from mild to life
      threatening, especially in immune-compromised individuals. HSV infections are
      commonly treated with the guanosine analogue Aciclovir, but reports of resistance
      are increasing. Efforts are made to establish single-stranded antisense
      oligodeoxynucleotides (as) and small interfering ribonucleic acids (siRNAs) for
      antiviral treatment. Recently, another class of short interfering nucleic acids,
      partially double-stranded hairpin loop-structured 54 mer oligodeoxynucleotides
      (ODNs), was shown to allow hydrolysis of HIV RNA by binding to the viral RNA.
      This leads to a substrate for the viral RNase H. To assess the potential of such
      ODNs for inhibition of HSV-1 replication, five partially double-stranded ODNs
      were designed based on the sequences of known siRNAs against HSV-1 with antiviral
      activity. Three of them are directed against early and two against leaky late
      genes. Primary human lung fibroblasts, MRC-5, and African green monkey kidney
      cells, Vero, were transfected with ODNs and subsequently infected. The effect on
      HSV-1 replication was determined by analyzing the virus titer in cell culture
      supernatants by quantitative PCR and plaque assays. An inhibitory effect was
      observed with all five selected ODNs, with two cases showing statistical
      significance in both cell types. The observed effect was sequence-specific and
      dose dependent. In one case the ODN was more efficient than a previously
      described siRNA directed against the same target site in the mRNA of UL5, a
      component of the helicase/primase complex. HSV-1 virions and ODNs can be applied
      simultaneously without transfection reagent, but at a 50-fold higher
      concentration to Vero cells with similar efficiencies. The results underline the
      potential of partially double-stranded hairpin loop-structured ODNs as antiviral
      agents.

PMID- 19397794
TI  - Survey-based naming conventions for use in OBO Foundry ontology development.
AB  - BACKGROUND: A wide variety of ontologies relevant to the biological and medical
      domains are available through the OBO Foundry portal, and their number is growing
      rapidly. Integration of these ontologies, while requiring considerable effort, is
      extremely desirable. However, heterogeneities in format and style pose serious
      obstacles to such integration. In particular, inconsistencies in naming
      conventions can impair the readability and navigability of ontology class
      hierarchies, and hinder their alignment and integration. While other sources of
      diversity are tremendously complex and challenging, agreeing a set of common
      naming conventions is an achievable goal, particularly if those conventions are
      based on lessons drawn from pooled practical experience and surveys of community
      opinion. RESULTS: We summarize a review of existing naming conventions and
      highlight certain disadvantages with respect to general applicability in the
      biological domain. We also present the results of a survey carried out to
      establish which naming conventions are currently employed by OBO Foundry
      ontologies and to determine what their special requirements regarding the naming
      of entities might be. Lastly, we propose an initial set of typographic, syntactic
      and semantic conventions for labelling classes in OBO Foundry ontologies.
      CONCLUSION: Adherence to common naming conventions is more than just a matter of
      aesthetics. Such conventions provide guidance to ontology creators, help
      developers avoid flaws and inaccuracies when editing, and especially when
      interlinking, ontologies. Common naming conventions will also assist consumers of
      ontologies to more readily understand what meanings were intended by the authors
      of ontologies used in annotating bodies of data.

PMID- 19397795
TI  - Effects of self-monitoring of glucose in non-insulin treated patients with type 2
      diabetes: design of the IN CONTROL-trial.
AB  - BACKGROUND: Diabetes specific emotional problems interfere with the demanding
      daily management of living with type 2 diabetes mellitus (T2DM). Possibly,
      offering direct feedback on diabetes management may diminish the presence of
      diabetes specific emotional problems and might enhance the patients' belief they
      are able to manage their illness. It is hypothesized that self-monitoring of
      glucose in combination with an algorithm how and when to act will motivate T2DM
      patients to become more active participants in their own care leading to a
      decrease in diabetes related distress and an increased self-efficacy. METHODS AND
      DESIGN: Six hundred patients with T2DM (45 < or = 75 years) who receive care in a
      structured diabetes care system, HbA1c > or = 7.0%, and not using insulin will be
      recruited and randomized into 3 groups; Self-monitoring of Blood Glucose (SMBG),
      Self-monitoring of Urine Glucose (SMUG) and usual care (n = 200 per group).
      Participants are eligible if they have a known disease duration of over 1 year
      and have used SMBG or SMUG less than 3 times in the previous year. All 3 groups
      will receive standardized diabetes care. The intervention groups will receive
      additional instructions on how to perform self-monitoring of glucose and how to
      interpret the results. Main outcome measures are changes in diabetes specific
      emotional distress and self-efficacy. Secondary outcome measures include
      difference in HbA1c, patient satisfaction, occurrence of hypoglycaemia, physical
      activity, costs of direct and indirect healthcare and changes in illness beliefs.
      DISCUSSION: The IN CONTROL-trial is designed to explore whether feedback from
      self-monitoring of glucose in T2DM patients who do not require insulin can affect
      diabetes specific emotional distress and increase self-efficacy. Based on the
      self-regulation model it is hypothesized that glucose self-monitoring feedback
      changes illness perceptions, guiding the patient to reduce emotional responses to
      experienced threats, and influences the patients ability to perform and maintain
      self-management skills.

PMID- 19397796
TI  - Improving the delivery of care for patients with diabetes through understanding
      optimised team work and organisation in primary care.
AB  - BACKGROUND: Type 2 diabetes is an increasingly prevalent chronic illness and is
      an important cause of avoidable mortality. Patients are managed by the integrated
      activities of clinical and non-clinical members of the primary care team. Studies
      of the quality of care for patients with diabetes suggest less than optimum care
      in a number of areas. AIM: The aim of this study is to improve the quality of
      care for patients with diabetes cared for in primary care in the UK by
      identifying individual, team, and organisational factors that predict the
      implementation of best practice. DESIGN: Participants will be clinical and non
      clinical staff within 100 general practices sampled from practices who are
      members of the MRC General Practice Research Framework. Self-completion
      questionnaires will be developed to measure the attributes of individual health
      care professionals, primary care teams (including both clinical and non-clinical
      staff), and their organisation in primary care. Questionnaires will be
      administered using postal survey methods. A range of validated theories will be
      used as a framework for the questionnaire instruments. Data relating to a range
      of dimensions of the organisational structure of primary care will be collected
      via a telephone interview at each practice using a structured interview schedule.
      We will also collect data relating to the processes of care, markers of
      biochemical control, and relevant indicator scores from the quality and outcomes
      framework (QOF). Process data (as a proxy indicator of clinical behaviours) will
      be collected from practice databases and via a postal questionnaire survey of a
      random selection of patients from each practice. Levels of biochemical control
      will be extracted from practice databases. A series of analyses will be conducted
      to relate the individual, team, and organisational data to the process, control,
      and QOF data to identify configurations associated with high quality care. STUDY
      REGISTRATION: UKCRN ref:DRN120 (ICPD).

PMID- 19397797
TI  - Anti-malarial prescriptions in three health care facilities after the emergence
      of chloroquine resistance in Niakhar, Senegal (1992-2004).
AB  - BACKGROUND: In the rural zone of Niakhar in Senegal, the first therapeutic
      failures for chloroquine (CQ) were observed in 1992. In 2003, the national policy
      regarding first-line treatment of uncomplicated malaria was modified, replacing
      CQ by a transitory bi-therapy amodiaquine/sulphadoxine-pyrimethamine (AQ/SP),
      before the implementation of artemisinin-based combination therapy (ACT) in 2006.
      The aims of the study were to assess the evolution of anti-malarial prescriptions
      in three health care facilities between 1992 and 2004, in parallel with
      increasing CQ resistance in the region. METHODS: The study was conducted in the
      area of Niakhar, a demographic surveillance site located in a sahelo-sudanese
      region of Senegal, with mesoendemic and seasonal malaria transmission. Health
      records of two public health centres and a private catholic dispensary were
      collected retrospectively to cover the period 1992-2004. RESULTS: Records
      included 110,093 consultations and 292,965 prescribed treatments. Twenty-five
      percent of treatments were anti-malarials, prescribed to 49% of patients. They
      were delivered all year long, but especially during the rainy season, and 20% of
      patients with no clinical malaria diagnosis received anti-malarials. Chloroquine
      and quinine represented respectively 55.7% and 34.6% of prescribed anti
      malarials. Overall, chloroquine prescriptions rose from 1992 to 2000, in parallel
      with clinical malaria; then the CQ prescription rate decreased from 2000 and was
      concomitant with the rise of SP and the persistence of quinine use. AQ and SP
      were mainly used as bi-therapy after 2003, at the time of national treatment
      policy change. CONCLUSION: The results show the overall level of anti-malarial
      prescription in the study area for a considerable number of patients over a large
      period of time. Even though resistance to CQ rapidly increased from 1992 to 2001,
      no change in CQ prescription was observed until the early 2000s, possibly due to
      the absence of an obvious decrease in CQ effectiveness, a lack of therapeutic
      options or a blind follow-up of national guidelines.

PMID- 19397799
TI  - An analysis of trends and determinants of health insurance and healthcare
      utilisation in the Russian population between 2000 and 2004: the 'inverse care
      law' in action.
AB  - BACKGROUND: The break-up of the USSR brought considerable disruption to health
      services in Russia. The uptake of compulsory health insurance rose rapidly after
      its introduction in 1993. However, by 2000 coverage was still incomplete,
      especially amongst the disadvantaged. By this time, however, the state health
      service had become more stable, and the private sector was growing. This paper
      describes subsequent trends and determinants of healthcare insurance coverage in
      Russia, and its relationship with health service utilisation, as well as the role
      of the private sector. METHODS: Data were from the Russia Longitudinal Monitoring
      Survey, an annual household panel survey (2000-4) from 38 centres across the
      Russian Federation. Annual trends in insurance coverage were measured (2000-4).
      Cross-sectional multivariate analyses of the determinants of health insurance and
      its relationship with health care utilisation were performed in working-age
      people (18-59 years) using 2004 data. RESULTS: Between 2000 and 2004, coverage by
      the compulsory insurance scheme increased from 88% to 94% of adults; however 10%
      of working-age men remained uninsured. Compulsory health insurance coverage was
      lower amongst the poor, unemployed, unhealthy and people outside the main cities.
      The uninsured were less likely to seek medical help for new health problems. 3%
      of respondents had supplementary (private) insurance, and rising utilisation of
      private healthcare was greatest amongst the more educated and wealthy.
      CONCLUSION: Despite high population insurance coverage, a multiply disadvantaged
      uninsured minority remains, with low utilisation of health services. Universal
      insurance could therefore increase access, and potentially contribute to reducing
      avoidable healthcare-related mortality. Meanwhile, the socioeconomically
      advantaged are turning increasingly to a growing private sector.

PMID- 19397798
TI  - Hip fractures and area level socioeconomic conditions: a population-based study.
AB  - BACKGROUND: Only a limited number of studies have analyzed the association
      between hip fracture incidence and socioeconomic conditions. Most, but not all
      found an association, and results are in part conflicting. The aim of our study
      was to evaluate the association between hip fractures and socioeconomic
      conditions in Germany, from 1995 to 2004, on a census tract area level. METHODS:
      We used data from the national hospital discharge diagnosis register and data on
      socioeconomic and demographic characteristics of 131 census tracts from official
      statistics. Associations between the hip fracture incidence and socioeconomic
      conditions were analyzed by multiple Poisson regression models, taking
      overdispersion into account. RESULTS: The risk of hip fracture decreased by 4%
      with a 7% increase (about one interquartile range) of non-German nationals. It
      decreased by 10% with a 6% increased rate of unemployment, increased by 7% with a
      2% increase of the proportion of welfare recipients, and also increased by 3%
      with an increase of the proportion of single parent families of 1.9%. CONCLUSION:
      Our results showed weak associations between indicators of socioeconomic
      conditions at area level and hip fracture risk; the varied by type of indicator.
      We conclude that hip fracture incidence might be influenced by the socioeconomic
      context of a region, but further analysis using more specific markers for
      deprivation on a smaller scale and individual-level data are needed.

PMID- 19397800
TI  - Validation of an abbreviated Treatment Satisfaction Questionnaire for Medication
      (TSQM-9) among patients on antihypertensive medications.
AB  - BACKGROUND: The 14-item Treatment Satisfaction Questionnaire for Medication
      (TSQM) Version 1.4 is a reliable and valid instrument to assess patients'
      satisfaction with medication, providing scores on four scales--side effects,
      effectiveness, convenience and global satisfaction. In naturalistic studies,
      administering the TSQM with the side effects domain could provoke the physician
      to assess the presence or absence of adverse events in a way that is clinically
      atypical, carrying the potential to interfere with routine medical care. As a
      result, an abbreviated 9-item TSQM (TSQM-9), derived from the TSQM Version 1.4
      but without the five items of the side effects domain was created. In this study,
      an interactive voice response system (IVRS)-administered TSQM-9 was
      psychometrically evaluated among patients taking antihypertensive medication.
      METHODS: A total of 3,387 subjects were invited to participate in the study from
      an online panel who self-reported taking a prescribed antihypertensive
      medication. The subjects were asked to complete the IVRS-administered TSQM-9 at
      the start of the study, along with the modified Morisky scale, and again within 7
      to 14 days. Standard psychometric analyses were conducted; including Cronbach's
      alpha, intraclass correlation coefficients, structural equation modeling,
      Spearman correlation coefficients and analysis of covariance (ANCOVA). RESULTS: A
      total of 396 subjects completed all the study procedures. Approximately 50%
      subjects were male with a good racial/ethnic mix: 58.3% white, 18.9% black, 17.7%
      Hispanic and 5.1% either Asian or other. There was evidence of construct validity
      of the TSQM-9 based on the structural equation modeling findings of the observed
      data fitting the Decisional Balance Model of Treatment Satisfaction even without
      the side effects domain. TSQM-9 domains had high internal consistency as evident
      from Cronbach's alpha values of 0.84 and greater. TSQM-9 domains also
      demonstrated good test-retest reliability with high intraclass correlation
      coefficients exceeding 0.70. As expected, the TSQM-9 domains were able to
      differentiate between individuals who were low, medium and high compliers of
      medication, with moderate to high effect sizes. There was evidence of convergent
      validity with significant correlations with the medication adherence scale.
      CONCLUSION: The IVRS-administered TSQM-9 was found to be a reliable and valid
      measure to assess treatment satisfaction in naturalistic study designs, in which
      there is potential that the administration of the side effects domain of the TSQM
      would interfere with routine clinical care.

PMID- 19397801
TI  - The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a
      genotype-phenotype association study.
AB  - BACKGROUND: The mitochondrial DNA (mtDNA) T16189C polymorphism, with a
      homopolymeric C-tract of 10-12 cytosines, is a putative genetic risk factor for
      idiopathic dilated cardiomyopathy in the African and British populations. We
      hypothesized that this variant may predispose to dilated cardiomyopathy in people
      who are infected with the human immunodeficiency virus (HIV). METHODS: A case
      control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV
      positive controls without dilated cardiomyopathy was conducted. The study was
      confined to persons of black African ancestry to minimize confounding of results
      by population admixture. HIV-positive patients with an echocardiographically
      confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with
      echocardiographically normal hearts were studied. Patients with secondary causes
      of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism,
      valvular heart disease, and opportunistic infection) were excluded from the
      study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a
      homopolymeric C-tract in the forward and reverse directions on an ABI3100
      sequencer. RESULTS: The cases and controls were well matched for age (median 35
      years versus 34 years, P = 0.93), gender (males 60% vs 53%, P = 0.54), and stage
      of HIV disease (mean CD4 T cell count 260.7/microL vs. 176/microL, P = 0.21). The
      mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of
      26.7% (8/30) in the HIV-associated cardiomyopathy cases and 13.5% (5/37) in the
      HIV-positive controls. There was no significant difference between cases and
      controls (Odds Ratio 2.33, 95% Confidence Interval 0.67-8.06, p = 0.11).
      CONCLUSION: The mtDNA T16189C variant with a homopolymeric C-tract is not
      associated with dilated cardiomyopathy in black African people infected with HIV.

PMID- 19397802
TI  - Inhibitors of apoptosis proteins (IAPs) expression and their prognostic
      significance in hepatocellular carcinoma.
AB  - BACKGROUND: Similarly to other tumor types, an imbalance between unrestrained
      cell proliferation and impaired apoptosis appears to be a major unfavorable
      feature of hepatocellular carcinoma (HCC). The members of IAP family are key
      regulators of apoptosis, cytokinesis and signal transduction. IAP survival action
      is antagonized by specific binding of Smac/DIABLO and XAF1. This study aimed to
      investigate the gene and protein expression pattern of IAP family members and
      their antagonists in a series of human HCCs and to assess their clinical
      significance. METHODS: Relative quantification of IAPs and their antagonist genes
      was assessed by quantitative Real Time RT-PCR (qPCR) in 80 patients who underwent
      surgical resection for HCC. The expression ratios of XIAP/XAF1 and of XIAP/Smac
      were also evaluated. Survivin, XIAP and XAF1 protein expression were investigated
      by immunohistochemistry. Correlations between mRNA levels, protein expression and
      clinicopathological features were assessed. Follow-up data were available for 69
      HCC patients. The overall survival analysis was estimated according to the Kaplan
      Meier method. RESULTS: Survivin and Livin/ML-IAP mRNAs were significantly over
      expressed in cancer tissues compared to non-neoplastic counterparts. Although
      Survivin immunoreactivity did not correlate with qPCR data, a significant
      relation was found between higher Survivin mRNA level and tumor stage, tumor
      grade and vascular invasion.The mRNA ratio XIAP/XAF1 was significantly higher in
      HCCs than in cirrhotic tissues. Moreover, high XIAP/XAF1 ratio was an indicator
      of poor prognosis when overall survival was estimated and elevated XIAP
      immunoreactivity was significantly associated with shorter survival. CONCLUSION:
      Our study demonstrates that alterations in the expression of IAP family members,
      including Survivin and Livin/ML-IAP, are frequent in HCCs. Of interest, we could
      determine that an imbalance in XIAP/XAF1 mRNA expression levels correlated to
      overall patient survival, and that high XIAP immunoreactivity was a poor
      prognostic factor.

PMID- 19397803
TI  - Identifying recombinants in human and primate immunodeficiency virus sequence
      alignments using quartet scanning.
AB  - BACKGROUND: Recombination has a profound impact on the evolution of viruses, but
      characterizing recombination patterns in molecular sequences remains a
      challenging endeavor. Despite its importance in molecular evolutionary studies,
      identifying the sequences that exhibit such patterns has received comparatively
      less attention in the recombination detection framework. Here, we extend a
      quartet-mapping based recombination detection method to enable identification of
      recombinant sequences without prior specifications of either query and reference
      sequences. Through simulations we evaluate different recombinant identification
      statistics and significance tests. We compare the quartet approach with triplet
      based methods that employ additional heuristic tests to identify parental and
      recombinant sequences. RESULTS: Analysis of phylogenetic simulations reveal that
      identifying the descendents of relatively old recombination events is a
      challenging task for all methods available, and that quartet scanning performs
      relatively well compared to the triplet based methods. The use of quartet
      scanning is further demonstrated by analyzing both well-established and putative
      HIV-1 recombinant strains. In agreement with recent findings, we provide evidence
      that the presumed circulating recombinant CRF02_AG is a 'pure' lineage, whereas
      the presumed parental lineage subtype G has a recombinant origin. We also
      demonstrate HIV-1 intrasubtype recombination, confirm the hybrid origin of SIV in
      chimpanzees and further disentangle the recombinant history of SIV lineages in a
      primate immunodeficiency virus data set. CONCLUSION: Quartet scanning makes a
      valuable addition to triplet-based methods for identifying recombinant sequences
      without prior specifications of either query and reference sequences. The new
      method is available in the VisRD v.3.0 package
      http://www.cmp.uea.ac.uk/~vlm/visrd.

PMID- 19397804
TI  - Communities of gastrointestinal helminths of fish in historically connected
      habitats: habitat fragmentation effect in a carnivorous catfish Pelteobagrus
      fulvidraco from seven lakes in flood plain of the Yangtze River, China.
AB  - BACKGROUND: Habitat fragmentation may result in the reduction of diversity of
      parasite communities by affecting population size and dispersal pattern of
      species. In the flood plain of the Yangtze River in China, many lakes, which were
      once connected with the river, have become isolated since the 1950s from the
      river by the construction of dams and sluices, with many larger lakes subdivided
      into smaller ones by road embankments. These artificial barriers have inevitably
      obstructed the migration of fish between the river and lakes and also among
      lakes. In this study, the gastrointestinal helminth communities were investigated
      in a carnivorous fish, the yellowhead catfish Pelteobagrus fulvidraco, from two
      connected and five isolated lakes in the flood plain in order to detect the
      effect of lake fragmentation on the parasite communities. RESULTS: A total of 11
      species of helminths were recorded in the stomach and intestine of P. fulvidraco
      from seven lakes, including two lakes connected with the Yangtze River, i.e.
      Poyang and Dongting lakes, and five isolated lakes, i.e. Honghu, Liangzi,
      Tangxun, Niushan and Baoan lakes. Mean helminth individuals and diversity of
      helminth communities in Honghu and Dongting lakes was lower than in the other
      five lakes. The nematode Procamallanus fulvidraconis was the dominant species of
      communities in all the seven lakes. No significant difference in the Shannon
      Wiener index was detected between connected lakes (0.48) and isolated lakes
      (0.50). The similarity of helminth communities between Niushan and Baoan lakes
      was the highest (0.6708), and the lowest was between Tangxun and Dongting lakes
      (0.1807). The similarity was low between Dongting and the other lakes, and the
      similarity decreased with the geographic distance among these lakes. The helminth
      community in one connected lake, Poyang Lake was clustered with isolated lakes,
      but the community in Dongting Lake was separated in the tree. CONCLUSION: The
      similarity in the helminth communities of this fish in the flood-plain lakes may
      be attributed to the historical connection of these habitats and to the
      completion of the life-cycles of this fish as well as the helminth species within
      the investigated habitats. The diversity and the digenean majority in the
      helminth communities can be related to the diet of this fish, and to the
      lacustrine and macrophytic characters of the habitats. The lake isolation from
      the river had little detectable effect on the helminth communities of the catfish
      in flood-plain lakes of the Yangtze River. The low similarities in helminth
      communities between the Dongting Lake and others may just be a reflection of its
      unique water environment and anthropogenic alterations or fragmentation in this
      lake.

PMID- 19397805
TI  - Fatal drug poisonings in a Swedish general population.
AB  - BACKGROUND: Pharmaceutical drug poisonings have previously been reported using
      single sources of information, either hospital data or forensic data, which might
      not reveal the true incidence. We therefore aimed to estimate the incidence of
      suspected fatal drug poisonings, defined as poisonings by pharmaceutical agents,
      by using all relevant case records from various sources in a Swedish population.
      METHODS: Every seventh randomly selected deceased in three counties in
      southeastern Sweden during a one-year period was identified in the Cause of Death
      Register. Relevant case records (death certificates, files from hospitals and/or
      primary care centres and medico-legal files) were reviewed for all study
      subjects. RESULTS: Of 1574 deceased study subjects, 12 cases were classified as
      pharmaceutical drug poisonings according to the death certificates and 10
      according to the medico-legal files. When reviewing all available data sources, 9
      subjects (0.57%; 95% confidence interval: 0.20-0.94%) were classified as drug
      poisonings, corresponding to an incidence of 6.5 (95% confidence interval: 2.3
      10.7) per 100,000 person-years in the general population. The drug groups most
      often implicated were benzodiazepines (33%), antihistamines (33%) and analgesics
      (22%). CONCLUSION: Fatal drug poisonings is a relatively common cause of death in
      Sweden. By using multiple sources of information when investigating the
      proportion of fatal poisonings in a population, more accurate estimates may be
      obtained.

PMID- 19397806
TI  - A typhoid fever outbreak in a slum of South Dumdum municipality, West Bengal,
      India, 2007: evidence for foodborne and waterborne transmission.
AB  - BACKGROUND: In April 2007, a slum of South Dumdum municipality, West Bengal
      reported an increase in fever cases. We investigated to identify the agent, the
      source and to propose recommendations. METHODS: We defined a suspected case of
      typhoid fever as occurrence of fever for > or = one week among residents of ward
      1 of South Dumdum during February - May 2007. We searched for suspected cases in
      health care facilities and collected blood specimens. We described the outbreak
      by time, place and person. We compared probable cases (Widal positive > or =
      1:80) with neighbourhood-matched controls. We assessed the environment and
      collected water specimens. RESULTS: We identified 103 suspected cases (Attack
      rate: 74/10,000, highest among 5-14 years old group, no deaths). Salmonella
      (enterica) Typhi was isolated from one of four blood specimens and 65 of 103 sera
      were > or = 1:80 Widal positive. The outbreak started on 13 February, peaked
      twice during the last week of March and second week of April and lasted till 27
      April. Suspected cases clustered around three public taps. Among 65 probable
      cases and 65 controls, eating milk products from a sweet shop (Matched odds ratio
      [MOR]: 6.2, 95% confidence interval [CI]: 2.4-16, population attributable
      fraction [PAF]: 53%) and drinking piped water (MOR: 7.3, 95% CI: 2.5-21, PAF-52%)
      were associated with illness. The sweet shop food handler suffered from typhoid
      in January. The pipelines of intermittent non-chlorinated water supply ran next
      to an open drain connected with sewerage system and water specimens showed faecal
      contamination. CONCLUSION: The investigation suggested that an initial foodborne
      outbreak of typhoid led to the contamination of the water supply resulting in a
      secondary, waterborne wave. We educated the food handler, repaired the pipelines
      and ensured chlorination of the water.

PMID- 19397807
TI  - Generation of Phaseolus vulgaris ESTs and investigation of their regulation upon
      Uromyces appendiculatus infection.
AB  - BACKGROUND: Phaseolus vulgaris (common bean) is the second most important legume
      crop in the world after soybean. Consequently, yield losses due to fungal
      infection, like Uromyces appendiculatus (bean rust), have strong consequences.
      Several resistant genes were identified that confer resistance to bean rust
      infection. However, the downstream genes and mechanisms involved in bean
      resistance to infection are poorly characterized. RESULTS: A subtractive bean
      cDNA library composed of 10,581 unisequences was constructed and enriched in
      sequences regulated by either bean rust race 41, a virulent strain, or race 49,
      an avirulent strain on cultivar Early Gallatin carrying the resistance gene Ur-4.
      The construction of this library allowed the identification of 6,202 new bean
      ESTs, significantly adding to the available sequences for this plant. Regulation
      of selected bean genes in response to bean rust infection was confirmed by qRT
      PCR. Plant gene expression was similar for both race 41 and 49 during the first
      48 hours of the infection process but varied significantly at the later time
      points (72-96 hours after inoculation) mainly due to the presence of the Avr4
      gene in the race 49 leading to a hypersensitive response in the bean plants. A
      biphasic pattern of gene expression was observed for several genes regulated in
      response to fungal infection. CONCLUSION: The enrichment of the public database
      with over 6,000 bean ESTs significantly adds to the genomic resources available
      for this important crop plant. The analysis of these genes in response to bean
      rust infection provides a foundation for further studies of the mechanism of
      fungal disease resistance. The expression pattern of 90 bean genes upon rust
      infection shares several features with other legumes infected by biotrophic
      fungi. This finding suggests that the P. vulgaris-U. appendiculatus pathosystem
      could serve as a model to explore legume-rust interaction.

PMID- 19397808
TI  - The limits of testing particle-mediated oxidative stress in vitro in predicting
      diverse pathologies; relevance for testing of nanoparticles.
AB  - In vitro studies with particles are a major staple of particle toxicology,
      generally used to investigate mechanisms and better understand the molecular
      events underlying cellular effects. However, there is ethical and financial
      pressure in nanotoxicology, the new sub-specialty of particle toxicology, to
      avoid using animals. Therefore an increasing amount of studies are being
      published using in vitro approaches and such studies require careful
      interpretation. We point out here that 3 different conventional pathogenic
      particle types, PM10, asbestos and quartz, which cause diverse pathological
      effects, have been reported to cause very similar oxidative stress effects in
      cells in culture. We discuss the likely explanation and implications of this
      apparent paradox, and its relevance for testing in nanotoxicology.

PMID- 19397809
TI  - Cell tracking and therapy evaluation of bone marrow monocytes and stromal cells
      using SPECT and CMR in a canine model of myocardial infarction.
AB  - BACKGROUND: The clinical application of stem cell therapy for myocardial
      infarction will require the development of methods to monitor treatment and pre
      clinical assessment in a large animal model, to determine its effectiveness and
      the optimum cell population, route of delivery, timing, and flow milieu.
      OBJECTIVES: To establish a model for a) in vivo tracking to monitor cell
      engraftment after autologous transplantation and b) concurrent measurement of
      infarct evolution and remodeling. METHODS: We evaluated 22 dogs (8 sham controls,
      7 treated with autologous bone marrow monocytes, and 7 with stromal cells) using
      both imaging of 111Indium-tropolone labeled cells and late gadolinium enhancement
      CMR for up to12 weeks after a 3 hour coronary occlusion. Hearts were also
      examined using immunohistochemistry for capillary density and presence of PKH26
      labeled cells. RESULTS: In vivo Indium imaging demonstrated an effective
      biological clearance half-life from the injection site of ~5 days. CMR
      demonstrated a pattern of progressive infarct shrinkage over 12 weeks, ranging
      from 67-88% of baseline values with monocytes producing a significant treatment
      effect. Relative infarct shrinkage was similar through to 6 weeks in all groups,
      following which the treatment effect was manifest. There was a trend towards an
      increase in capillary density with cell treatment. CONCLUSION: This multi
      modality approach will allow determination of the success and persistence of
      engraftment, and a correlation of this with infarct size shrinkage, regional
      function, and left ventricular remodeling. There were overall no major treatment
      effects with this particular model of transplantation immediately post-infarct.

PMID- 19397810
TI  - Undiagnosed osteoid osteoma of the spine presenting as painful scoliosis from
      adolescence to adulthood: a case report.
AB  - Presented here is a case of a young woman, with an undiagnosed osteoid osteoma of
      the spine, which presented with painful scoliosis in adolescence and was treated
      by bracing until her accession to adulthood. A more thorough investigation, years
      after the initial one, revealed the tumor. Surgical excision and stabilization
      offered the long-awaited cure. Misdiagnosis resulted in intractable pain for
      years, deformity, the discomfort of brace therapy, and the frustration of a
      prolonged yet ineffective treatment.

PMID- 19397811
TI  - Overdose beliefs and management practices among ethnic Vietnamese heroin users in
      Sydney, Australia.
AB  - BACKGROUND: Ethnic Vietnamese injecting drug users (IDUs) in Australia draw on a
      range of beliefs and etiologic models, sometimes simultaneously, in order to make
      sense of health and illness. These include understandings of illness as the
      result of internal imbalances and Western concepts of disease causation including
      germ/pollution theory. METHODS: Observational fieldwork and in-depth interviews
      were conducted between 2001 and 2006 in neighbourhoods characterised by high
      proportions of Asian background IDUs and street-based drug markets. Eligibility
      criteria for the study were: 1) ethnic Vietnamese cultural background; 2) aged 16
      years and over and; 3) injected drugs in the last 6 months. RESULTS: Participants
      commonly attempted to treat heroin overdose by withdrawing blood (rut mau) from
      the body. Central to this practice are cultural beliefs about the role and
      function of blood in the body and its relationship to illness and health.
      Participants' beliefs in blood were strongly influenced by understandings of
      blood expressed in traditional Chinese and Vietnamese medicine. Many participants
      perceived Western drugs, particularly heroin, as "hot" and "strong". In overdose
      situations, it was commonly believed that an excessive amount of drugs
      (particularly heroin) entered the bloodstream and traveled to the heart, making
      the heart work too hard. Withdrawing blood was understood to reduce the amount of
      drugs in the body which in turn reduced the effects of drugs on the blood and the
      heart. CONCLUSION: The explanatory model of overdose employed by ethnic
      Vietnamese IDUs privileges traditional beliefs about the circulatory, rather than
      the respiratory, system. This paper explores participants' beliefs about blood,
      the effects of drugs on blood and the causes of heroin overdose in order to
      document the explanatory model of overdose used by ethnic Vietnamese IDUs.
      Implications for overdose prevention, treatment and management are identified and
      discussed.

PMID- 19397812
TI  - Soluble aggregates of the amyloid-beta peptide are trapped by serum albumin to
      enhance amyloid-beta activation of endothelial cells.
AB  - BACKGROUND: Self-assembly of the amyloid-beta peptide (Abeta) has been implicated
      in the pathogenesis of Alzheimer's disease (AD). As a result, synthetic molecules
      capable of inhibiting Abeta self-assembly could serve as therapeutic agents and
      endogenous molecules that modulate Abeta self-assembly may influence disease
      progression. However, increasing evidence implicating a principal pathogenic role
      for small soluble Abeta aggregates warns that inhibition at intermediate stages
      of Abeta self-assembly may prove detrimental. Here, we explore the inhibition of
      Abeta1-40 self-assembly by serum albumin, the most abundant plasma protein, and
      the influence of this inhibition on Abeta1-40 activation of endothelial cells for
      monocyte adhesion. RESULTS: It is demonstrated that serum albumin is capable of
      inhibiting in a dose-dependent manner both the formation of Abeta1-40 aggregates
      from monomeric peptide and the ongoing growth of Abeta1-40 fibrils. Inhibition of
      fibrillar Abeta1-40 aggregate growth is observed at substoichiometric
      concentrations, suggesting that serum albumin recognizes aggregated forms of the
      peptide to prevent monomer addition. Inhibition of Abeta1-40 monomer aggregation
      is observed down to stoichiometric ratios with partial inhibition leading to an
      increase in the population of small soluble aggregates. Such partial inhibition
      of Abeta1-40 aggregation leads to an increase in the ability of resulting
      aggregates to activate endothelial cells for adhesion of monocytes. In contrast,
      Abeta1-40 activation of endothelial cells for monocyte adhesion is reduced when
      more complete inhibition is observed. CONCLUSION: These results demonstrate that
      inhibitors of Abeta self-assembly have the potential to trap small soluble
      aggregates resulting in an elevation rather than a reduction of cellular
      responses. These findings provide further support that small soluble aggregates
      possess high levels of physiological activity and underscore the importance of
      resolving the effect of Abeta aggregation inhibitors on aggregate size.

PMID- 19397813
TI  - Familial history of diabetes and clinical characteristics in Greek subjects with
      type 2 diabetes.
AB  - BACKGROUND: A lot of studies have showed an excess maternal transmission of type
      2 diabetes (T2D). The aim, therefore, of the present study was to estimate the
      prevalence of familial history of T2D in Greek patients, and to evaluate its
      potential effect on the patient's metabolic control and the presence of diabetic
      complications. METHODS: A total of 1,473 T2D patients were recruited. Those with
      diabetic mothers, diabetic fathers, diabetic relatives other than parents and no
      known diabetic relatives, were considered separately. RESULTS: The prevalence of
      diabetes in the mother, the father and relatives other than parents, was 27.7,
      11.0 and 10.7%, respectively. Patients with paternal diabetes had a higher
      prevalence of hypertension (64.8 vs. 57.1%, P = 0.05) and lower LDL-cholesterol
      levels (115.12 +/- 39.76 vs. 127.13 +/- 46.53 mg/dl, P = 0.006) than patients
      with diabetes in the mother. Patients with familial diabetes were significantly
      younger (P < 0.001), with lower age at diabetes diagnosis (P < 0.001) than those
      without diabetic relatives. Patients with a diabetic parent had higher body mass
      index (BMI) (31.22 +/- 5.87 vs. 30.67 +/- 5.35 Kg/m2, P = 0.08), higher
      prevalence of dyslipidemia (49.8 vs. 44.6%, P = 0.06) and retinopathy (17.9 vs.
      14.5%, P = 0.08) compared with patients with no diabetic relatives. No difference
      in the degree of metabolic control and the prevalence of chronic complications
      were observed. CONCLUSION: The present study showed an excess maternal
      transmission of T2D in a sample of Greek diabetic patients. However, no different
      influence was found between maternal and paternal diabetes on the clinical
      characteristics of diabetic patients except for LDL-cholesterol levels and
      presence of hypertension. The presence of a family history of diabetes resulted
      to an early onset of the disease to the offspring.

PMID- 19397814
TI  - Tumor-directed gene therapy in mice using a composite nonviral gene delivery
      system consisting of the piggyBac transposon and polyethylenimine.
AB  - BACKGROUND: Compared with viral vectors, nonviral vectors are less immunogenic,
      more stable, safer and easier to replication for application in cancer gene
      therapy. However, nonviral gene delivery system has not been extensively used
      because of the low transfection efficiency and the short transgene expression,
      especially in vivo. It is desirable to develop a nonviral gene delivery system
      that can support stable genomic integration and persistent gene expression in
      vivo. Here, we used a composite nonviral gene delivery system consisting of the
      piggyBac (PB) transposon and polyethylenimine (PEI) for long-term transgene
      expression in mouse ovarian tumors. METHODS: A recombinant plasmid PB [Act-RFP,
      HSV-tk] encoding both the herpes simplex thymidine kinase (HSV-tk) and the
      monomeric red fluorescent protein (mRFP1) under PB transposon elements was
      constructed. This plasmid and the PBase plasmid were injected into ovarian cancer
      tumor xenografts in mice by in vivo PEI system. The antitumor effects of HSV
      tk/ganciclovir (GCV) system were observed after intraperitoneal injection of GCV.
      Histological analysis and TUNEL assay were performed on the cryostat sections of
      the tumor tissue. RESULTS: Plasmid construction was confirmed by PCR analysis
      combined with restrictive enzyme digestion. mRFP1 expression could be visualized
      three weeks after the last transfection of pPB/TK under fluorescence microscopy.
      After GCV admission, the tumor volume of PB/TK group was significantly reduced
      and the tumor inhibitory rate was 81.96% contrasted against the 43.07% in the TK
      group. Histological analysis showed that there were extensive necrosis and
      lymphocytes infiltration in the tumor tissue of the PB/TK group but limited in
      the tissue of control group. TUNEL assays suggested that the transfected cells
      were undergoing apoptosis after GCV admission in vivo. CONCLUSION: Our results
      show that the nonviral gene delivery system coupling PB transposon with PEI can
      be used as an efficient tool for gene therapy in ovarian cancer.

PMID- 19397815
TI  - Differential orientation effect in the neural response to interacting biological
      motion of two agents.
AB  - BACKGROUND: A recent behavioral study demonstrated that the meaningful
      interaction of two agents enhances the detection sensitivity of biological motion
      (BM), however, it remains unclear when and how the 'interaction' information of
      two agents is represented in our neural system. To clarify this point, we used
      magnetoencephalography and introduced a novel experimental technique to extract a
      neuromagnetic response relating to two-agent BM perception. We then investigated
      how this response was modulated by the interaction of two agents. In the present
      experiment, we presented two kinds of visual stimuli (interacting and non
      interacting BM) with two orientations (upright and inverted). RESULTS: We found a
      neuromagnetic response in the bilateral occipitotemporal region, on average 300 -
      400 ms after the onset of a two-agent BM stimulus. This result showed that
      interhemispheric differences were apparent for the peak amplitudes. For the left
      hemisphere, the orientation effect was manifest when the two agents were made to
      interact, and the interaction effect was manifest when the stimulus was inverted.
      In the right hemisphere, the main effects of both orientation and interaction
      were significant, suggesting that the peak amplitude was attenuated when the
      visual stimulus was inverted or made to interact. CONCLUSION: These results
      demonstrate that the 'interaction' information of two agents can affect the
      neural activities in the bilateral occipitotemporal region, on average 300 - 400
      ms after the onset of a two-agent BM stimulus, however, the modulation was
      different between hemispheres: the left hemisphere is more concerned with
      dynamics, whereas the right hemisphere is more concerned with form information.

PMID- 19397816
TI  - Recruitment to a physical activity intervention study in women at increased risk
      of breast cancer.
AB  - BACKGROUND: Physical activity is being studied as a breast cancer prevention
      strategy. Women at risk of breast cancer report interest in lifestyle
      modification, but recruitment to randomized physical activity intervention
      studies is challenging. METHODS: We conducted an analysis of recruitment
      techniques used for a prospective, randomized pilot study of physical activity in
      women at risk of breast cancer. We evaluated differences in proportion of
      eligible patients, enrolled patients, and successful patients identified by each
      individual recruitment method. The Fisher-Freeman-Halton test (an extension of
      Fisher's exact test from 2 x 2 tables to general row by column tables) was used
      to compare the success of different recruitment strategies. RESULTS: We received
      352 inquiries from women interested in participating, of whom 171 (54%) were
      eligible. Ninety-nine women completed a baseline activity evaluation, and 58 (34%
      of eligible; 16% of total inquiries) were randomized. Recruitment methods fell
      into three broad categories: media techniques, direct contact with potential
      participants, and contacts with health care providers. Recruitment strategies
      differed significantly in their ability to identify eligible women (p = 0.01),
      and women who subsequently enrolled in the study (p = 0.02). CONCLUSION:
      Recruitment techniques had varying success. Our data illustrate the challenges in
      recruiting to behavior modification studies, and provide useful information for
      tailoring future recruitment efforts for lifestyle intervention trials. TRIAL
      REGISTRATION NO(S): CDR0000393790, NCI-04-C-0276, NCI-NAVY-B05-001.

PMID- 19397817
TI  - Parallel DNA pyrosequencing unveils new zebrafish microRNAs.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a new class of small RNAs of approximately 22
      nucleotides in length that control eukaryotic gene expression by fine tuning mRNA
      translation. They regulate a wide variety of biological processes, namely
      developmental timing, cell differentiation, cell proliferation, immune response
      and infection. For this reason, their identification is essential to understand
      eukaryotic biology. Their small size, low abundance and high instability
      complicated early identification, however cloning/Sanger sequencing and new
      generation genome sequencing approaches overcame most technical hurdles and are
      being used for rapid miRNA identification in many eukaryotes. RESULTS: We have
      applied 454 DNA pyrosequencing technology to miRNA discovery in zebrafish (Danio
      rerio). For this, a series of cDNA libraries were prepared from miRNAs isolated
      at different embryonic time points and from fully developed organs. Each cDNA
      library was tagged with specific sequences and was sequenced using the Roche FLX
      genome sequencer. This approach retrieved 90% of the 192 miRNAs previously
      identified by cloning/Sanger sequencing and bioinformatics. Twenty five novel
      miRNAs were predicted, 107 miRNA star sequences and also 41 candidate miRNA
      targets were identified. A miRNA expression profile built on the basis of
      pyrosequencing read numbers showed high expression of most miRNAs throughout
      zebrafish development and identified tissue specific miRNAs. CONCLUSION: This
      study increases the number of zebrafish miRNAs from 192 to 217 and demonstrates
      that a single DNA mini-chip pyrosequencing run is effective in miRNA
      identification in zebrafish. This methodology also produced sufficient
      information to elucidate miRNA expression patterns during development and in
      differentiated organs. Moreover, some zebrafish miRNA star sequences were more
      abundant than their corresponding miRNAs, suggesting a functional role for the
      former in gene expression control in this vertebrate model organism.

PMID- 19397818
TI  - Molecular profiles of Quadriceps muscle in myostatin-null mice reveal PI3K and
      apoptotic pathways as myostatin targets.
AB  - BACKGROUND: Myostatin (MSTN), a member of the TGF-beta superfamily, has been
      identified as a negative regulator of skeletal muscle mass. Inactivating
      mutations in the MSTN gene are responsible for the development of a hypermuscular
      phenotype. In this study, we performed transcriptomic and proteomic analyses to
      detect altered expression/abundance of genes and proteins. These differentially
      expressed genes and proteins may represent new molecular targets of MSTN and
      could be involved in the regulation of skeletal muscle mass. RESULTS:
      Transcriptomic analysis of the Quadriceps muscles of 5-week-old MSTN-null mice (n
      = 4) and their controls (n = 4) was carried out using microarray (human and
      murine oligonucleotide sequences) of 6,473 genes expressed in muscle. Proteomic
      profiles were analysed using two-dimensional gel electrophoresis coupled with
      mass spectrometry. Comparison of the transcriptomic profiles revealed 192 up- and
      245 down- regulated genes. Genes involved in the PI3K pathway, insulin/IGF
      pathway, carbohydrate metabolism and apoptosis regulation were up-regulated.
      Genes belonging to canonical Wnt, calcium signalling pathways and cytokine
      receptor cytokine interaction were down-regulated. Comparison of the protein
      profiles revealed 20 up- and 18 down-regulated proteins spots. Knockout of the
      MSTN gene was associated with up-regulation of proteins involved in glycolytic
      shift of the muscles and down-regulation of proteins involved in oxidative energy
      metabolism. In addition, an increased abundance of survival/anti-apoptotic
      factors were observed. CONCLUSION: All together, these results showed a
      differential expression of genes and proteins related to the muscle energy
      metabolism and cell survival/anti-apoptotic pathway (e.g. DJ-1, PINK1, 14-3
      3epsilon protein, TCTP/GSK-3beta). They revealed the PI3K and apoptotic pathways
      as MSTN targets and are in favour of a role of MSTN as a modulator of cell
      survival in vivo.

PMID- 19397819
TI  - Gene set internal coherence in the context of functional profiling.
AB  - BACKGROUND: Functional profiling methods have been extensively used in the
      context of high-throughput experiments and, in particular, in microarray data
      analysis. Such methods use available biological information to define different
      types of functional gene modules (e.g. gene ontology -GO-, KEGG pathways, etc.)
      whose representation in a pre-defined list of genes is further studied. In the
      most popular type of microarray experimental designs (e.g. up- or down-regulated
      genes, clusters of co-expressing genes, etc.) or in other genomic experiments
      (e.g. Chip-on-chip, epigenomics, etc.) these lists are composed by genes with a
      high degree of co-expression. Therefore, an implicit assumption in the
      application of functional profiling methods within this context is that the genes
      corresponding to the modules tested are effectively defining sets of co
      expressing genes. Nevertheless not all the functional modules are biologically
      coherent entities in terms of co-expression, which will eventually hinder its
      detection with conventional methods of functional enrichment. RESULTS: Using a
      large collection of microarray data we have carried out a detailed survey of
      internal correlation in GO terms and KEGG pathways, providing a coherence index
      to be used for measuring functional module co-regulation. An unexpected low level
      of internal correlation was found among the modules studied. Only around 30% of
      the modules defined by GO terms and 57% of the modules defined by KEGG pathways
      display an internal correlation higher than the expected by chance.This
      information on the internal correlation of the genes within the functional
      modules can be used in the context of a logistic regression model in a simple way
      to improve their detection in gene expression experiments. CONCLUSION: For the
      first time, an exhaustive study on the internal co-expression of the most popular
      functional categories has been carried out. Interestingly, the real level of
      coexpression within many of them is lower than expected (or even inexistent),
      which will preclude its detection by means of most conventional functional
      profiling methods. If the gene-to-function correlation information is used in
      functional profiling methods, the results obtained improve the ones obtained by
      conventional enrichment methods.

PMID- 19397820
TI  - A description of a knowledge broker role implemented as part of a randomized
      controlled trial evaluating three knowledge translation strategies.
AB  - BACKGROUND: A knowledge broker (KB) is a popular knowledge translation and
      exchange (KTE) strategy emerging in Canada to promote interaction between
      researchers and end users, as well as to develop capacity for evidence-informed
      decision making. A KB provides a link between research producers and end users by
      developing a mutual understanding of goals and cultures, collaborates with end
      users to identify issues and problems for which solutions are required, and
      facilitates the identification, access, assessment, interpretation, and
      translation of research evidence into local policy and practice. Knowledge
      brokering can be carried out by individuals, groups and/or organizations, as well
      as entire countries. In each case, the KB is linked with a group of end users and
      focuses on promoting the integration of the best available evidence into policy
      and practice-related decisions. METHODS: A KB intervention comprised one of three
      KTE interventions evaluated in a randomized controlled trial. RESULTS: KB
      activities were classified into the following categories: initial and ongoing
      needs assessments; scanning the horizon; knowledge management; KTE; network
      development, maintenance, and facilitation; facilitation of individual capacity
      development in evidence informed decision making; and g) facilitation of and
      support for organizational change. CONCLUSION: As the KB role developed during
      this study, central themes that emerged as particularly important included
      relationship development, ongoing support, customized approaches, and
      opportunities for individual and organizational capacity development. The novelty
      of the KB role in public health provides a unique opportunity to assess the need
      for and reaction to the role and its associated activities. Future research
      should include studies to evaluate the effectiveness of KBs in different settings
      and among different health care professionals, and to explore the optimal
      preparation and training of KBs, as well as the identification of the personality
      characteristics most closely associated with KB effectiveness. Studies should
      also seek to better understand which combination of KB activities are associated
      with optimal evidence-informed decision making outcomes, and whether the
      combination changes in different settings and among different health care
      decision makers.

PMID- 19397821
TI  - Context dependent reference states of solvent accessibility derived from native
      protein structures and assessed by predictability analysis.
AB  - BACKGROUND: Solvent accessibility (ASA) of amino acid residues is often
      transformed from absolute values of exposed surface area to their normalized
      relative values. This normalization is typically attained by assuming a highest
      exposure conformation based on extended state of that residue when it is
      surrounded by Ala or Gly on both sides i.e. Ala-X-Ala or Gly-X-Gly solvent
      exposed area. Exact sequence context, the folding state of the residues, and the
      actual environment of a folded protein, which do impose additional constraints on
      the highest possible (or highest observed) values of ASA, are currently ignored.
      Here, we analyze the statistics of these constraints and examine how the
      normalization of absolute ASA values using context-dependent Highest Observed ASA
      (HOA) instead of context-free extended state ASA (ESA) of residues can influence
      the performance of sequence-based prediction of solvent accessibility.
      Characterization of burial and exposed states of residues based on this
      normalization has also been shown to provide better enrichment of DNA-binding
      sites in exposed residues. RESULTS: We compiled the statistics of highest
      observed ASA (HOA) of residues in their different contexts and analyzed their
      distribution in all 400 possible combinations for each residue type. We observe
      that many trippetides are more exposed than ESA and that HOA residues are often
      found in turn, coil and bend conformations. On the other hand several residues
      are never observed in an exposure state close to ESA values. A neural networks
      trained with HOA-normalized data outperforms the one trained with ESA-normalized
      values. However, the improvements are subtle in some residues, while they are
      more significant in others. CONCLUSION: HOA based normalization of solvent
      accessibility from native structures is proposed and it shows improvement in
      sequence-based predictability, as well as enrichment in interface residues on
      surface. There may still be some difference between the highest possible ASA and
      highest observed ASA due to an insufficiently covered space of ASA distribution
      in the PDB, which limit the overall improvement in prediction to a relatively
      modest degree.

PMID- 19397822
TI  - Differential intracellular fate of Burkholderia pseudomallei 844 and Burkholderia
      thailandensis UE5 in human monocyte-derived dendritic cells and macrophages.
AB  - BACKGROUND: Burkholderia pseudomallei (Bp) is a category B biothreat organism
      that causes a potentially fatal disease in humans and animals, namely
      melioidosis. Burkholderia thailandensis (Bt) is another naturally occurring
      species that is very closely related to Bp. However, despite this closely related
      genotype, Bt is considered avirulent as it does not cause the disease. In the
      present study, we compared the growth kinetics of B. pseudomallei strain 844 (Bp
      844) in human monocyte-derived dendritic cells (MoDCs) and macrophages (Mphis),
      as well as its ability to stimulate host cell responses with those of B.
      thailandensis strain UE5 (Bt-UE5). RESULTS: Primary human MoDCs and Mphis were
      infected with Bp-844 and its intracellular growth kinetics and ability to induce
      host cell responses were evaluated. The results were compared with those obtained
      using the Bt-UE5. In human MoDCs, both bacteria were similar in respect to their
      ability to survive and replicate intracellularly, induce upregulation of
      costimulatory molecules and cytokines and bias T helper cell differentiation
      toward a Th1 phenotype. By contrast, the two bacteria exhibited different growth
      kinetics in human Mphis, where the intracellular growth of Bt-UE5, but not Bp
      844, was significantly suppressed. Moreover, the ability of Mphis to kill Bp-844
      was markedly enhanced following stimulation with IFN-gamma. CONCLUSION: The data
      presented showed that while both strains were similar in their ability to survive
      and replicate in human MoDCs, only Bp-844 could readily replicate in human Mphis.
      Both bacteria induced similar host cellular responses, particularly with regard
      to their ability to bias T cell differentiation toward a Th1 phenotype.

PMID- 19397823
TI  - Genetic dissection of MHC-associated susceptibility to Lepeophtheirus salmonis in
      Atlantic salmon.
AB  - BACKGROUND: Genetic variation has been shown to play a significant role in
      determining susceptibility to the salmon louse, Lepeophtheirus salmonis. However,
      the mechanisms involved in differential response to infection remain poorly
      understood. Recent findings in Atlantic salmon (Salmo salar) have provided
      evidence for a potential link between marker variation at the major
      histocompatibility complex (MHC) and differences in lice abundance among infected
      siblings, suggesting that MHC genes can modulate susceptibility to the parasite.
      In this study, we used quantitative trait locus (QTL) analysis to test the effect
      of genomic regions linked to MHC class I and II on linkage groups (LG) 15 and 6,
      respectively. RESULTS: Significant QTL effects were detected on both LG 6 and LG
      15 in sire-based analysis but the QTL regions remained unresolved due to a lack
      of recombination between markers. In dam-based analysis, a significant QTL was
      identified on LG 6, which accounted for 12.9% of within-family variance in lice
      abundance. However, the QTL was located at the opposite end of DAA, with no
      significant overlap with the MHC class II region. Interestingly, QTL modelling
      also revealed evidence of sex-linked differences in lice abundance, indicating
      that males and females may have different susceptibility to infection.
      CONCLUSION: Overall, QTL analysis provided relatively weak support for a proximal
      effect of classical MHC regions on lice abundance, which can partly be explained
      by linkage to other genes controlling susceptibility to L. salmonis on the same
      chromosome.

PMID- 19397824
TI  - Potentials of on-line repositioning based on implanted fiducial markers and
      electronic portal imaging in prostate cancer radiotherapy.
AB  - BACKGROUND: To evaluate the benefit of an on-line correction protocol based on
      implanted markers and weekly portal imaging in external beam radiotherapy of
      prostate cancer. To compare the use of bony anatomy versus implanted markers for
      calculation of setup-error plus/minus prostate movement. To estimate the error
      reduction (and the corresponding margin reduction) by reducing the total error to
      3 mm once a week, three times per week or every treatment day. METHODS: 23
      patients had three to five, 2.5 mm O spherical gold markers transrectally
      inserted into the prostate before radiotherapy. Verification and correction of
      treatment position by analysis of orthogonal portal images was performed on a
      weekly basis. We registered with respect to the bony contours (setup error) and
      to the marker position (prostate motion) and determined the total error. The
      systematic and random errors are specified. Positioning correction was applied
      with a threshold of 5 mm displacement. RESULTS: The systematic error (1 standard
      deviation [SD]) in left-right (LR), superior-inferior (SI) and anterior-posterior
      (AP) direction contributes for the setup 1.6 mm, 2.1 mm and 2.4 mm and for
      prostate motion 1.1 mm, 1.9 mm and 2.3 mm. The random error (1 SD) in LR, SI and
      AP direction amounts for the setup 2.3 mm, 2.7 mm and 2.7 mm and for motion 1.4
      mm, 2.3 mm and 2.7 mm. The resulting total error suggests margins of 7.0 mm (LR),
      9.5 mm (SI) and 9.5 mm (AP) between clinical target volume (CTV) and planning
      target volume (PTV). After correction once a week the margins were lowered to
      6.7, 8.2 and 8.7 mm and furthermore down to 4.9, 5.1 and 4.8 mm after correcting
      every treatment day. CONCLUSION: Prostate movement relative to adjacent bony
      anatomy is significant and contributes substantially to the target position
      variability. Performing on-line setup correction using implanted radioopaque
      markers and megavoltage radiography results in reduced treatment margins
      depending on the online imaging protocol (once a week or more frequently).

PMID- 19397825
TI  - Identification of potentially safe promising fungal cell factories for the
      production of polyketide natural food colorants using chemotaxonomic rationale.
AB  - BACKGROUND: Colorants derived from natural sources look set to overtake synthetic
      colorants in market value as manufacturers continue to meet the rising demand for
      clean label ingredients - particularly in food applications. Many ascomycetous
      fungi naturally synthesize and secrete pigments and thus provide readily
      available additional and/or alternative sources of natural colorants that are
      independent of agro-climatic conditions. With an appropriately selected fungus;
      using in particular chemotaxonomy as a guide, the fungal natural colorants could
      be produced in high yields by using the optimized cultivation technology. This
      approach could secure efficient production of pigments avoiding use of genetic
      manipulation. RESULTS: Polyketide pigment producing ascomycetous fungi were
      evaluated for their potential as production organisms based on a priori knowledge
      on species-specific pigment and potential mycotoxin production and BioSafety
      level (BSL) classification. Based on taxonomic knowledge, we pre-selected
      ascomycetous fungi belonging to Penicillium subgenus Biverticillium that produced
      yellow, orange or red pigments while deselecting Penicillium marneffei; a well
      known human pathogen in addition to other mycotoxigenic fungi belonging to the
      same group. We identified 10 strains belonging to 4 species; viz. P.
      purpurogenum, P. aculeatum, P. funiculosum, and P. pinophilum as potential
      pigment producers that produced Monascus-like pigments but no known mycotoxins.
      The selection/deselection protocol was illustrated in the pigment extracts of P.
      aculeatum IBT 14259 and P. crateriforme IBT 5015 analysed by HPLC-DAD-MS. In
      addition, extracellular pigment producing ability of some of the potential
      pigment producers was evaluated in liquid media with a solid support and N
      glutarylmonascorubramine was discovered in the partially purified pigment extract
      of P. purpurogenum IBT 11181 and IBT 3645. CONCLUSION: The present work brought
      out that the use of chemotaxonomic tools and a priori knowledge of fungal
      extrolites is a rational approach towards selection of fungal polyketide pigment
      producers considering the enormous chemical diversity and biodiversity of
      ascomycetous fungi. This rationale could be very handy for the selection of
      potentially safe fungal cell factories not only for polyketide pigments but also
      for the other industrially important polyketides; the molecular and genetic basis
      for the biosynthesis of which has not yet been examined in detail. In addition, 4
      out of the 10 chemotaxonomically selected promising Penicillium strains were
      shown to produce extracellular pigments in the liquid media using a solid support
      indicating future cell factory possibilities for polyketide natural food
      colorants.

PMID- 19397826
TI  - M-protein and other intrinsic virulence factors of Streptococcus pyogenes are
      encoded on an ancient pathogenicity island.
AB  - BACKGROUND: The increasing number of completely sequenced bacterial genomes
      allows comparing their architecture and genetic makeup. Such new information
      highlights the crucial role of lateral genetic exchanges in bacterial evolution
      and speciation. RESULTS: Here we analyzed the twelve sequenced genomes of
      Streptococcus pyogenes by a naive approach that examines the preferential
      nucleotide usage along the chromosome, namely the usage of G versus C (GC-skew)
      and T versus A (TA-skew). The cumulative GC-skew plot presented an inverted V
      shape composed of two symmetrical linear segments, where the minimum and maximum
      corresponded to the origin and terminus of DNA replication. In contrast, the
      cumulative TA-skew presented a V-shape, which segments were interrupted by
      several steep slopes regions (SSRs), indicative of a different nucleotide
      composition bias. Each S. pyogenes genome contained up to nine individual SSRs,
      encompassing all described strain-specific prophages. In addition, each genome
      contained a similar unique non-phage SSR, the core of which consisted of 31
      highly homologous genes. This core includes the M-protein, other mga-related
      factors and other virulence genes, totaling ten intrinsic virulence genes. In
      addition to a high content in virulence-related genes and to a peculiar
      nucleotide bias, this SSR, which is 47 kb-long in a M1GAS strain, harbors direct
      repeats and a tRNA gene, suggesting a mobile element. Moreover, its complete
      absence in a M-protein negative group A Streptococcus natural isolate
      demonstrates that it could be spontaneously lost, but in vitro deletion
      experiments indicates that its excision occurred at very low rate. The stability
      of this SSR, combined to its presence in all sequenced S. pyogenes sequenced
      genome, suggests that it results from an ancient acquisition. CONCLUSION: Thus,
      this non-phagic SSR is compatible with a pathogenicity island, acquired before S.
      pyogenes speciation. Its potential excision might bear relevance for vaccine
      development, because vaccines targeting M-protein might select for M-protein
      negative variants that still carry other virulence determinants.

PMID- 19397828
TI  - Altered gene expression and miRNA expression associated with cancerous IEC-6 cell
      transformed by MNNG.
AB  - BACKGROUND: Tumorigenesis is thought to be the consequence of gene mutation and
      disordered gene expression. However, the detailed molecular mechanism underlying
      the development and progress of colon cancer have not been elucidate completely.
      This study aimed to find out the genes associated with cancer biological pathways
      involved in transformation and tumorigenesis. METHODS: Normal intestinal cell
      line 6 (IEC-6) cells were transformed to cancer cells by treatment with
      cancerogenic agent of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and Phorbol 12
      myristate 13 acetate (PMA). Then we investigated the altered gene expression of
      transformed IEC-6 cells by the microarray containing 113 genes associated with
      cancer pathway. Also the altered miRNAs of transformed IEC-6 cells were analyzed
      by array hybridization (miRCURY Array v9.2, Exiqon). The levels of acetylated
      histone H3 in transformed IEC-6 cells was evaluated by western blot. RESULTS:
      Cell proliferation was significantly increased as IEC-6 cells were transformed
      and tumor xenografts could be detected in animals as transformed IEC-6 cells were
      inoculated subcutaneously in nude mice. Result of microarray showed nine genes
      were increased and two decreased, as well as 13 miRNA were increased and 97
      decreased. Verification by real-time PCR implies that the data obtained from
      microarray analysis were reliable. Western blot showed the levels of acetylated
      histone H3 were increased dramatically after MNNG/PMA treatment. CONCLUSION: Our
      results showed many important biological pathways and miRNAs were involved in
      transformation and tumorigenesis of IEC-6 cells, which suggested the
      transformation of normal cells was involved with large mount of genetic and
      epigenetic variation.

PMID- 19397827
TI  - The Ontario Mother and Infant Study (TOMIS) III: a multi-site cohort study of the
      impact of delivery method on health, service use, and costs of care in the first
      postpartum year.
AB  - BACKGROUND: The caesarean section rate continues to rise globally. A caesarean
      section is inarguably the preferred method of delivery when there is good
      evidence that a vaginal delivery may unduly risk the health of a woman or her
      infant. Any decisions about delivery method in the absence of clear medical
      indication should be based on knowledge of outcomes associated with different
      childbirth methods. However, there is lack of sold evidence of the short-term and
      long-term risks and benefits of a planned caesarean delivery compared to a
      planned vaginal delivery. It also is important to consider the economic aspects
      of caesarean sections, but very little attention has been given to health care
      system costs that take into account services used by women for themselves and
      their infants following hospital discharge. METHODS AND DESIGN: The Ontario
      Mother and Infant Study III is a prospective cohort study to examine
      relationships between method of delivery and maternal and infant health, service
      utilization, and cost of care at three time points during the year following
      postpartum hospital discharge. Over 2500 women were recruited from 11 hospitals
      across the province of Ontario, Canada, with data collection occurring between
      April 2006 and October 2008. Participants completed a self-report questionnaire
      in hospital and structured telephone interviews at 6 weeks, 6 months, and 12
      months after discharge. Data will be analyzed using generalized estimating
      equation, a special generalized linear models technique. A qualitative
      descriptive component supplements the survey approach, with the goal of assisting
      in interpretation of data and providing explanations for trends in the findings.
      DISCUSSION: The findings can be incorporated into patient counselling and
      discussions about the advantages and disadvantages of different delivery methods,
      potentially leading to changes in preferences and practices. In addition, the
      findings will be useful to hospital- and community-based postpartum care
      providers, managers, and administrators in guiding risk assessment and early
      intervention strategies. Finally, the research findings can provide the basis for
      policy modification and implementation strategies to improve outcomes and reduce
      costs of care.

PMID- 19397829
TI  - Proteins of the origin recognition complex (ORC) and DNA topoisomerases on
      mammalian chromatin.
AB  - BACKGROUND: The process of DNA replication requires the separation of
      complementary DNA strands. In this process, the unwinding of circularly closed or
      long DNA duplices leads to torsional tensions which must be released by
      topoisomerases. So topoisomerases play an important role in DNA replication. In
      order to provide more information about topoisomerases in the initiation of
      mammalian replication, we investigated whether topoisomerases occur close to ORC
      in the chromatin of cultured human HeLa cells. RESULTS: We have used different
      cell fractionation procedures, namely salt and nuclease treatment of isolated
      nuclei as well as formaldehyde-mediated cross-linking of chromatin, to
      investigate the distribution of topoisomerases and proteins of the origin
      recognition complex (ORC) in the chromatin of human HeLa cells. First we obtained
      no evidence for a physical interaction of either topoisomerase I or topoisomerase
      II with ORC. Then we found, however, that (Orc1-5) and topo II occurred together
      on chromatin fragments of 600 and more bp lengths. At last we showed that both
      topo II and Orc2 protein are enriched near the origin at the human MCM4 gene, and
      at least some of the topo II at the origin is active in proliferating HeLa cells.
      So taken together, topoisomerase II, but not topoisomerase I, is located close to
      ORC on chromatin. CONCLUSION: Topoisomerase II is more highly expressed than ORC
      proteins in mammalian cells, so only a small fraction of total chromatin-bound
      topoisomerase II was found in the vicinity of ORC. The precise position of topo
      II relative to ORC may differ among origins.

PMID- 19397830
TI  - Flow cytometric analysis of CK19 expression in the peripheral blood of breast
      carcinoma patients: relevance for circulating tumor cell detection.
AB  - BACKGROUND: Immunocytochemistry and RT-PCR have been widely used for the
      detection of circulating tumor cells in patients with breast cancer but their
      specificity is limited. Our purpose is to utilize a convenient and specific
      technology to detect circulating tumor cells in breast cancer patients. METHODS:
      To determine the sensitivity and specificity of our method, A431 cells were
      serially diluted with human peripheral blood leukocytes and stained with CK19. A
      total of 73 blood specimens including 25 healthy volunteers and 48 patients with
      breast carcinoma and benign tumor were tested by flow cytometry to quantify the
      expression of CK19. RESULTS: The detectable upper limit of A431 cells was 1
      cancer cell among 104 human white blood cells. CK19 was detected in 27% of breast
      cancer patients but none control gives positive result. The number of cancer
      cells increased gradually along with the disease stages for it was the least in
      stage I (0%) and the most in stage IV (1.29%). Fifteen patients were observed
      during three month chemotherapy after surgery, and most of their CK19 expression
      levels declined after treatment. CONCLUSION: Our research convinces that the
      detection of CK19 in peripheral blood by flow cytometry is also a specific and
      feasible method to monitor circulating tumor cells in breast cancer.

PMID- 19397831
TI  - Bipolar disorder and dopamine dysfunction: an indirect approach focusing on
      tardive movement syndromes in a naturalistic setting.
AB  - BACKGROUND: It has been suggested that dopamine dysfunction may play a role in
      bipolar disorder (BD). An indirect approach to examine this issue was developed,
      focusing on associations between dopamine proxy measures observed in BD (dopamine
      related clinical traits using tardive movement syndromes as dopamine proxy
      measure of reference). METHODS: 3459 eligible bipolar patients were enrolled in
      an observational study. Incidence rates of tardive movement syndromes (tardive
      dyskinesia and tardive dystonia; TDD) were examined. A priori hypothesized
      associations between incident TDD and other dopamine proxies (e.g. prolactin
      related adverse effects, bipolar symptoms) were tested over a 2 year follow-up
      period. RESULTS: The incidence rate of tardive syndromes was 4.1 %. Incident TDD
      was independently associated not only with use of antipsychotics, but also with
      more severe bipolar symptoms, other extrapyramidal symptoms and prolactin-related
      adverse effects of medication. CONCLUSION: Apart from the well-known association
      with antipsychotics, development of TDD was associated with various other
      dopamine proxy measures, indirectly supporting the notion of generalised dopamine
      dysregulation in BD.

PMID- 19397832
TI  - Host immune responses to chlamydial inclusion membrane proteins B and C in
      Chlamydia trachomatis infected women with or without fertility disorders.
AB  - BACKGROUND: With an increase in the number of putative inclusion membrane
      proteins (incs) in chlamydial genomes, there is a need for understanding their
      contribution in host-pathogen interactions. Thus in this study we determined the
      host mucosal and peripheral immune responses to incs (IncB and IncC) of Chlamydia
      trachomatis (CT). METHODS: Female patients (n = 296) attending the gynaecology
      out patient department of Safdarjung hospital, New Delhi were enrolled for the
      study and were clinically characterized into two groups; CT-positive fertile
      women (n = 38) and CT-positive women with fertility disorders (n = 29).
      Uninfected healthy fertile women were enrolled as controls (n = 31). Gene
      specific PCRs were used for detection of incB and incC genes in endocervical
      samples of CT-positive patients. ELISA and Western blot assay were used for
      detection of IgA and IgG antibodies to IncB and IncC in cervical washes and sera.
      Effect of IncB and IncC stimulation of cervical cells and PBMCs on cellular
      proliferation and cytotoxity was determined using MTT assay and Lactate
      dehydrogenase (LDH)-cytotoxicity assay respectively. Modulation of cytokines
      (Interleukin (IL)-1 Beta, IL-4, IL-5, IL-6, IL-10, Interferon-gamma, IL-12, Tumor
      Necrosis Factor-alpha and Granulocyte macrophage colony-stimulating factor (GM
      CSF)) in cervical cells and PBMCs upon stimulation with IncB and IncC was
      determined by real-time reverse-transcriptase (RT)-PCR and ELISA. Further, CD4
      positive T cells were purified from cervical cells and peripheral blood
      mononuclear cells (PBMCs) and secreted cytokines (Interferon-gamma and IL-4) were
      evaluated by ELISPOT and real-time RT-PCR. RESULTS: Using MTT assay,
      significantly high proliferative responses (P < 0.05) were observed in inc
      stimulated cervical cells and PBMCs from CT-positive fertile women compared to CT
      positive women with fertility disorders and controls. Interferon-gamma, IL-12 and
      GM-CSF were found to be elevated in inc-stimulated cervical cells and PBMCs of CT
      positive fertile women compared to CT-positive women with fertility disorders and
      controls (P < 0.05). In contrast, IL-1 Beta, IL-4, IL-5, IL-6 and IL-10 levels
      were found to be higher in CT-positive women with fertility disorders compared to
      CT-positive fertile women and controls (P < 0.05). Interferon-gamma secreting
      cells and mRNA expression in inc-stimulated cervical and peripheral CD4 positive
      T cells were significantly higher (P < 0.05) in CT positive fertile women
      compared to CT-positive women with fertility disorders. CONCLUSION: Our data
      overall suggests that CT incs, IncB and IncC modulate host immune responses and
      may have a role in protection/pathogenesis of genital chlamydial infection in
      women.

PMID- 19397833
TI  - Clinical relevance of heparin-PF4 complex antibody in DVT after total joint
      replacement.
AB  - BACKGROUND: Antibodies to the heparin-platelet factor-4 (HPF-4) complex (HIT
      antibodies) have been observed in patients with heparin-induced thrombocytopenia
      (HIT). These antibodies are thought to be involved in thrombosis through
      activation of platelet/endothelial cells. This prospective study was conducted to
      determine the incidence of post-operative HIT antibodies to assess the associated
      risk of deep vein thrombosis (DVT) in patients undergoing total knee arthroplasty
      (TKA) or total hip arthroplasty (THA). METHODS: We studied 104 patients who
      underwent unilateral primary TKA (n = 44) and primary THA (n = 60) with short
      duration prophylaxis (1-2 days of a fixed dose of unfractionated heparin). HIT
      antibodies were assayed using a sandwich-type ELISA before the operation and
      after heparin treatment (post-operative day 7). RESULTS: In the clinical outcome,
      the incidence of symptomatic DVT was 15.4% (16/104, TKA; 10, THA 6) and pulmonary
      embolism (PE) was not observed. The total seroconversion rate of HIT antibodies
      at post-operative day 7 was 34.6% (36/104). Among 36 seroconverted patients, 11
      (30.6%) developed symptomatic DVT and 5 out of 68 of the non-seroconverted
      patients (7.4%) developed symptomatic DVT. The incidence for DVT was
      significantly higher in the seroconverted patients compared with that of the non
      seroconverted patients (odds ratio 5.5, 95%CI: 1.7-17.6 p = 0.0028). Furthermore,
      in the patients with symptomatic DVT, the titer of HIT antibodies at post
      operative day 7 was significantly higher compared with those without symptomatic
      DVT. CONCLUSION: Our data therefore suggest that seroconversion for HIT
      antibodies generated by heparin is associated with a risk of DVT in patients
      undergoing total joint replacement.

PMID- 19397834
TI  - Intimate partner violence and depression among women in rural Ethiopia: a cross
      sectional study.
AB  - BACKGROUND: Studies from high-income countries have shown intimate partner
      violence to be associated with depression among women. The present paper examines
      whether this finding can be confirmed in a very different cultural setting in
      rural Ethiopia. METHOD: A community-based cross-sectional study was undertaken in
      Ethiopia among 1994 currently married women. Using the Composite International
      Diagnostic Interview (CIDI), cases of depressive episode were identified
      according to the ICD-10 diagnosis. Using a standardized questionnaire, women who
      experienced violence by an intimate partner were identified. A multivariate
      analysis was conducted between the explanatory variables and depressive status of
      the women, after adjusting for possible confounders. RESULTS: The 12-month
      prevalence of depressive episode among the women was 4.8% (95% CI, 3.9% and
      5.8%), while the lifetime prevalence of any form of intimate partner violence was
      72.0% (95% CI, 70.0% and 73.9%). Physical violence (OR = 2.56, 95% CI, 1.61,
      4.06), childhood sexual abuse (OR = 2.00, 95% CI, 1.13, 3.56), mild emotional
      violence (OR = 3.19, 95% CI, 1.98, 5.14), severe emotional violence (OR = 3.90,
      95% CI, 2.20, 6.93) and high spousal control of women (OR = 3.30, 95% CI, 1.58,
      6.90) by their partners were independently associated with depressive episode,
      even after adjusting for socioeconomic factors. CONCLUSION: The high prevalence
      of intimate partner violence, a factor often obscured within general life event
      categories, requires attention to consider it as an independent factor for
      depression, and thus to find new possibilities of prevention and treatment in
      terms of public health strategies, interventions and service provision.

PMID- 19397835
TI  - Evaluation of Gram-positive rod surveillance for early anthrax detection.
AB  - Since 2003, Connecticut laboratories have reported Gram-positive rod (GPR)
      isolates detected within 32 h of inoculation from blood or cerebrospinal fluid.
      The objectives were to rapidly identify inhalational anthrax and unusual
      Clostridium spp. infections, and to establish round-the-clock laboratory
      reporting of potential indicators of bioterrorism. From 2003 to 2006,
      Connecticut's GPR surveillance system identified 1134 isolates, including 657
      Bacillus spp. (none B. anthracis) and 241 Clostridium spp. Reporting completeness
      and timeliness improved to 93% and 92%, respectively. Baseline rates of Bacillus
      spp., Clostridium spp. and other GPR findings have been established and are
      stable. Thus far, no cases of anthrax and no unusual clusters of Clostridium spp.
      have been detected by the GPR surveillance system. This system would probably
      have confirmed the inhalational anthrax case in Pennsylvania in 2006 3 days
      sooner than traditional reporting. Using audits and ongoing evaluation, the
      system has evolved into a highly functional 24/7 laboratory telephone reporting
      system with almost complete reporting.

PMID- 19397836
TI  - Marine n-3 fatty acids promote size reduction of visceral adipose depots, without
      altering body weight and composition, in male Wistar rats fed a high-fat diet.
AB  - We evaluated the effects of partly substituting lard with marine n-3 fatty acids
      (FA) on body composition and weight, adipose tissue distribution and gene
      expression in five adipose depots of male Wistar rats fed a high-fat diet. Rats
      were fed diets including lard (19.5 % lard) or n-3 FA (9.1 % lard and 10.4 %
      Triomar) for 7 weeks. Feed consumption and weight gain were similar, whereas
      plasma lipid concentrations were lower in the n-3 FA group. Magnetic resonance
      imaging revealed smaller visceral (mesenteric, perirenal and epididymal) adipose
      depots in the n-3 FA-fed animals (35, 44 and 32 % reductions, respectively). n-3
      FA feeding increased mRNA expression of cytokines as well as chemokines in
      several adipose depots. Expression of Adipoq and Pparg was enhanced in the
      mesenteric adipose depots of the n-3 FA-fed rats, and fasting plasma insulin
      levels were lowered. Expression of the lipogenic enzymes Acaca and Fasn was
      increased in the visceral adipose depots, whereas Dgat1 was reduced in the
      perirenal and epididymal depots. Cpt2 mRNA expression was almost doubled in the
      mesenteric depot and liver. Carcass analyses showed similar body fat (%) in the
      two feeding groups, indicating that n-3 FA feeding led to redistribution of fat
      away from the visceral compartment.

PMID- 19397837
TI  - Dietary diacylglycerol oil has no effect on hypertriacylglycerolaemia in
      lipoprotein lipase-deficient cats.
AB  - A commercially available vegetable oil containing a high concentration (87 %,
      w/w) of diacylglycerol (DAG) has been investigated in humans and animals for
      potential beneficial effects in reducing serum TAG concentrations in fasting and
      postprandial states. Effects of DAG oil as a sole dietary fat source (25 %
      metabolisable energy) were evaluated in a feline model of
      hypertriacylglycerolaemia. Eleven adult (1.5 (sem 0.1) years) male cats deficient
      of lipoprotein lipase (LPL) catalytic activity from a heritable point mutation of
      the LPL gene were acclimatised to a semi-purified diet containing TAG oil for 21
      d. After assignment into two groups, pair-matched by serum TAG concentrations
      (range 6.1-31.6 mmol/l), the cats were fed the diet with either TAG or DAG oil
      for 8 d. The dietary fat source was crossed-over and presented for 8 d more. Non
      fasting serum concentrations of TAG, cholesterol and NEFA were measured on days 6
      8 and days 14-16. Dietary fat source (DAG v. TAG) did not significantly affect
      food intake (491 (sem 16) v. 486 (sem 14) kJ/kg0.67), body weight or serum
      concentrations (mmol/l) of TAG (37.1 (sem 4.5) v. 33.9 (sem 3.4)), cholesterol
      (4.8 (sem 0.3) v. 4.8 (sem 0.2)) and NEFA (1.4 (sem 0.2) v. 1.4 (sem 0.2)). The
      results show that for a feeding trial of 8 d, DAG oil was well accepted and
      tolerated by cats but did not reduce hypertriacylglycerolaemia resulting from a
      deficiency of LPL catalytic activity.

PMID- 19397838
TI  - Transcription factors in the pathogenesis of diabetic nephropathy.
AB  - Approximately a third of patients with diabetes develop diabetic kidney disease,
      and diabetes is the leading cause of end-stage renal disease in most developed
      countries. Hyperglycaemia is known to activate genes that ultimately lead to
      extracellular matrix accumulation, the hallmark of diabetic nephropathy. Several
      transcription factors have been implicated in glucose-mediated expression of
      genes involved in diabetic nephropathy. This review focuses on the transcription
      factors upstream stimulatory factors 1 and 2 (USF1 and 2), activator protein 1
      (AP-1), nuclear factor (NF)-kappaB, cAMP-response-element-binding protein (CREB),
      nuclear factor of activated T cells (NFAT), and stimulating protein 1 (Sp1). In
      response to high glucose, several of these transcription factors regulate the
      gene encoding the profibrotic cytokine transforming growth factor beta, as well
      as genes for a range of other proteins implicated in inflammation and
      extracellular matrix turnover, including thrombospondin 1, the chemokine CCL2,
      osteopontin, fibronectin, decorin, plasminogen activator inhibitor 1 and aldose
      reductase. Identifying the molecular mechanisms by which diabetic nephropathy
      occurs has important clinical implications as therapies can then be tailored to
      target those at risk. Strategies to specifically target transcription factor
      activation and function may be employed to halt the progression of diabetic
      nephropathy.

PMID- 19397839
TI  - In vitro fertilization efficiency in coral Acropora digitifera.
AB  - We performed fertilization experiments with Acropora digitifera, which is one of
      the dominant scleractinian corals in the Ryukyu Archipelago, Japan, to determine
      optimal conditions for in vitro manipulations. Our result suggests that
      conspecific fertilization is essentially complete within 30 min under the
      experimental conditions used in usual fertilization experiments in corals.
      Previous in vitro experiments (1 x 10(5)-10(6) sperm/ml, 4-8 h) are likely to
      have overestimated the efficiency of fertilization of Acropora spp. in the field.
      Therefore, we suggest that incubation periods shorter than those used to date
      (i.e. complete exclusion of sperm 1 h after their addition) would be more
      appropriate for the estimation of fertilization rates in corals.

PMID- 19397840
TI  - Subcellular localization of calcium and Ca-ATPase activity during nuclear
      maturation in Bufo arenarum oocytes.
AB  - The localization of calcium and Ca-ATPase activity in Bufo arenarum oocytes was
      investigated by ultracytochemical techniques during progesterone-induced nuclear
      maturation, under in vitro conditions. No Ca2+ deposits were detected in either
      control oocytes or progesterone-treated ones for 1-2 h. At the time when nuclear
      migration started, electron dense deposits of Ca2+ were visible in vesicles,
      endoplasmic reticulum cisternae and in the space between the annulate lamellae
      membranes. Furthermore, Ca-ATPase activity was also detected in these membrane
      structures. As maturation progressed, the cation deposits were observed in the
      cytomembrane structures, which underwent an important reorganization and
      redistribution. Thus, they moved from the subcortex and became located
      predominantly in the oocyte cortex area when nuclear maturation ended. Ca2+
      stores were observed in vesicles surrounding or between the cortical granules,
      which are aligned close to the plasma membrane. The positive Ca-ATPase reaction
      in these membrane structures could indicate that the calcium deposit is an ATP
      dependent process. Our results suggest that during oocyte maturation calcium
      would be stored in membrane structures where it remains available for release at
      the time of fertilization. Data obtained under our experimental conditions
      indicate that calcium from the extracellular medium would be important for the
      oocyte maturation process.

PMID- 19397841
TI  - Modifications of chemically induced-enucleated nuclear transfer technique by
      reverse-order nuclear transfer in mouse.
AB  - To improve the developmental potential of somatic cell cloned embryos derived
      from demecolcine (DC) induced-enucleated nuclear transfer (INT), we modified the
      INT procedures by transferring donor nuclei into recipient cytoplasts prior to
      the induced enucleation of the recipient cytoplasts, and we called this modified
      INT technique as reverse-order and induced-enucleated nuclear transfer (RINT).
      Standard nuclear transfer (SNT) and INT were performed as controls. The dynamic
      changes of maternal and transferred donor nuclei in the RINT oocytes were
      monitored to evaluate the feasibility of this new nuclear transfer (NT) technique
      by timed immunofluorescence. Timed immunofluorescence showed that RINT is
      feasible because none of the transferred donor nuclei were expelled with the
      second polar body (Pb) in the RINT oocytes, while 42.2% of the oocytes showed
      extrusion of all maternal chromosome and spindles with the second Pb at 60 min
      after activation and DC treatment. Although there was no difference in cleavage
      rate (86.6% vs. 82.1%), the rates of successful enucleation and blastocyst
      formation were significantly increased in RINT compared with INT (44.1% vs. 27.5%
      and 43.3% vs. 12.8%, respectively; p < 0.01). Compared with SNT, there was no
      difference in cleavage rate (86.6% vs. 78.4%), but the blastocyst developmental
      rate was significantly increased in the RINT group (43.3% vs. 25.3%; p < 0.01).
      Blastocysts derived from RINT had a higher total cell number than those from SNT
      (45.1 +/- 3 vs. 37.6 +/- 4; p < 0.05). Our results provide evidence that RINT is
      feasible and may provide a more efficient and simple method for NT than INT.

PMID- 19397842
TI  - Apoptotic processes and DNA cytosine methylation in mouse embryos arrested at the
      2-cell stage.
AB  - The present study evaluates the role of apoptotic cell death and DNA methylation
      reprogramming in early developmental failures occurring in embryos at the 2-cell
      stage. Mouse 2-cell embryos were cultured in vitro and treated with chemicals
      that cause developmental arrest and apoptosis (alpha-amanitin, actinomycin D, TNF
      alpha). After 24 h, 48 h and 72 h culture, embryos were analysed using cell-death
      assays (annexin V staining, TUNEL labelling and immunodetection of active caspase
      3) and genome methylation assay (immunodetection of 5-methylcytosine). The
      ability of embryos at the 2-cell stage to undergo apoptotic processes was very
      low. In arrested embryos, the presence of all evaluated features of apoptosis was
      recorded only after 72 h culture and their incidence was sporadical.
      Interestingly, the most frequently observed apoptotic sign was nuclear
      condensation and the timing of its appearance preceded even the
      phosphatidylserine flip. Both normally developing and arrested embryos displayed
      reduction in DNA cytosine methylation. In arrested embryos, this process was
      independent of cellular cleavage, was more pronounced and finished in almost
      complete demethylation of the embryonic genome. The timing of the demethylation
      overlapped with the onset of major apoptotic events. Although observed apoptotic
      cells showed either demethylated or methylated DNA cytosine in their nuclei, at
      blastocyst stage the demethylated status appeared more frequently in them.

PMID- 19397843
TI  - Being there with others: how people make environments norm-relevant.
AB  - In two studies we show that people make environments norm-relevant and this
      increases the likelihood that environments influence norm-relevant judgments.
      When people see environments without having people on their mind, this effect
      does not occur. Specifically, when exposed to an environment (a library),
      people's perceived importance of environment-relevant norms (be silent in
      libraries) increases, when the concept of 'people' is primed compared to when
      this is not the case. The impact on normative judgments of priming significant
      others (Study 1) is stronger than priming people in general (Study 2). Additional
      effects on conformism and public self-consciousness are discussed, as well as
      implications for future studies.

PMID- 19397844
TI  - Different meanings of the social dominance orientation concept: predicting
      political attitudes over time.
AB  - We examined predictors of political attitude change by assessing the independent
      and interactive effect of social dominance orientation (SDO) as a context
      dependent versus an individual difference construct. In a longitudinal study,
      British students' political orientation was assessed before entering university
      (T1) and after being at university for 2 months (T2) and 6 months (T3; N=109).
      Results showed that initial SDO (T1) did not predict political attitudes change
      nor did it predict self-selected entry into course with hierarchy enhancing or
      hierarchy-attenuating ideologies. More support was obtained for a contextually
      determined model whereby SDO (T2) mediated the relationship between social class
      (T1) and political attitude change (T3). We also found support for mediated
      moderation in accounting for effects of initial SDO on political attitude change.
      Findings suggest that SDO as a concept that is sensitive to group dynamics is
      best suited to explain shifts in political attitudes.

PMID- 19397845
TI  - Altruism as a courtship display: some effects of third-party generosity on
      audience perceptions.
AB  - Public generosity may be a means to convincingly advertise one's good character.
      This hypothesis suggests that altruistic individuals will be desirable as
      romantic partners. Few studies have tested this prediction, and these showed
      mixed results. Some studies have found that altruism is not particularly
      attractive; other studies showed that altruism is attractive by contrasting
      descriptions of 'nice guys' with 'jerks'. The present study sought to resolve
      this debate by having participants read a series of experimentally manipulated
      vignettes of persons with corresponding photographs, such that altruistic
      vignettes were compared with control descriptions that differed only in the
      presence or absence of small hints of altruistic tendencies. Altruists were more
      desirable for long-term relationships than neutral individuals. Women also
      preferred altruists for single dates whereas men had no such preference. These
      results are discussed with regard to the idea that people (males in particular)
      signal their good character via generosity.

PMID- 19397846
TI  - A method of bias correction for maximal reliability with dichotomous measures.
AB  - This paper is concerned with the reliability of weighted combinations of a given
      set of dichotomous measures. Maximal reliability for such measures has been
      discussed in the past, but the pertinent estimator exhibits a considerable bias
      and mean squared error for moderate sample sizes. We examine this bias, propose a
      procedure for bias correction, and develop a more accurate asymptotic confidence
      interval for the resulting estimator. In most empirically relevant cases, the
      bias correction and mean squared error correction can be performed
      simultaneously. We propose an approximate (asymptotic) confidence interval for
      the maximal reliability coefficient, discuss the implementation of this
      estimator, and investigate the mean squared error of the associated asymptotic
      approximation. We illustrate the proposed methods using a numerical example.

PMID- 19397847
TI  - In-task and post-task affective response to exercise: translating exercise
      intentions into behaviour.
AB  - OBJECTIVES: To test whether affective response to an acute bout of exercise can
      predict regular voluntary exercise, and specifically whether a positive affective
      response helps translate intentions into behaviour. DESIGN: A prospective
      correlational design. METHODS: Participants (N=127) recruited from the community
      reported intentions to engage in voluntary exercise and frequency of
      participation in voluntary exercise both at baseline and at a 3-month follow-up.
      Self-reported positive affect, negative affect, tranquillity, and fatigue were
      assessed during a bout of moderate intensity exercise. RESULTS: Within subject
      slopes for increases in positive affect and decreases in fatigue during exercise,
      and increased tranquillity and decreased fatigue post-exercise were associated
      with more frequent participation in exercise at follow-up. Changes in negative
      affect did not predict exercise at follow-up; however, this was likely due to
      floor effects leading to lack of baseline variability in negative affect.
      Importantly, a positive affective response to exercise moderated the intention
      behaviour relationship, such that those who responded to exercise more favourably
      exhibited stronger relationships between intentions and future exercise behaviour
      Conclusions: We conclude that exercise-related increases in positive affect and
      tranquillity and decreases in feelings of fatigue can aid in the successful
      translation of exercise intentions into behaviour.

PMID- 19397848
TI  - Social-cognitive difficulties in former users of methamphetamine.
AB  - OBJECTIVES: Methamphetamine (MA) abuse is associated with neurocognitive
      impairment. We investigated whether important aspects of social-cognitive
      function are similarly disrupted. METHODS: A total of 12 adults with a history of
      MA dependence (average duration of use, 3.9 years), currently engaged in
      rehabilitation and abstinent for an average period of 6 months, and 12 MA naive
      participants completed measures of facial affect recognition, theory of mind,
      executive function and memory. RESULTS: MA users were impaired on the measures of
      facial affect recognition and theory of mind (ds = 1.75 and 2.32, respectively),
      with the magnitude of these deficits comparable or larger to those observed on
      the cognitive measures. CONCLUSIONS: Social-cognitive difficulties are associated
      with MA use and have potentially important implications for rehabilitative
      practice.

PMID- 19397849
TI  - Neuroleptics in the treatment of aggressive challenging behaviour for people with
      intellectual disabilities: a randomised controlled trial (NACHBID).
AB  - OBJECTIVE(S): To assess the effects and cost-effectiveness of haloperidol,
      risperidone and placebo on aggressive challenging behaviour in adults with
      intellectual disability. DESIGN: A double-blind randomised controlled trial of
      two drugs and placebo administered in flexible dosage, with full, independent
      assessments of aggressive and aberrant behaviour, global improvement, carer
      burden, quality of life and adverse drug effects at baseline, 4, 12 and 26 weeks,
      and comparison of total care costs in the 6 months before and after
      randomisation. At 12 weeks, patients were given the option of leaving the trial
      or continuing until 26 weeks. Assessments of observed aggression were also
      carried out with key workers at weekly intervals throughout the trial. SETTING:
      Patients were recruited from all those being treated by intellectual disability
      services in eight sites in England, one in Wales and one in Queensland,
      Australia. PARTICIPANTS: Patients from all severity levels of intellectual
      disability; recruitment was extended to include those who may have been treated
      with neuroleptic drugs in the past. EXCLUSION CRITERIA: treatment with depot
      neuroleptics/another form of injected neuroleptic medication within the last 3
      months; continuous oral neuroleptic medication within the last week; those under
      a section of the Mental Health Act 1983 or Queensland Mental Health Act 2000.
      INTERVENTIONS: Randomisation to treatment with haloperidol (a typical neuroleptic
      drug), risperidone (an atypical neuroleptic drug) or placebo using a permuted
      blocks procedure. Dosages were: haloperidol 1.25-5.0 mg daily; risperidone 0.5
      2.0 mg daily. MAIN OUTCOME MEASURES: Primary: reduction in aggressive episodes
      between baseline and 4 weeks using Modified Overt Aggression Scale. Secondary:
      Aberrant Behaviour Checklist; Uplift/Burden Scale; 40-item Quality of Life
      Questionnaire; Udvalg for Kliniske Undersogelser scale; Clinical Global
      Impressions scale. Economic costs recorded using a modified version of Client
      Service Receipt Inventory for 6 months before and after randomisation. RESULTS:
      There were considerable difficulties in recruitment because of ethical and
      consent doubts. Twenty-two clinicians recruited a total of 86 patients. Mean
      daily dosages were 1.07 mg rising to 1.78 mg for risperidone and 2.54 mg rising
      to 2.94 mg for haloperidol. Aggression declined dramatically with all three
      treatments by 4 weeks, with placebo showing the greatest reduction (79%, versus
      57% for combined drugs) (p = 0.06). Placebo-treated patients showed no evidence
      of inferior response in comparison to patients receiving neuroleptic drugs. An
      additional study found that clinicians who had not participated in clinical
      trials before were less likely to recruit. Mean total cost of accommodation,
      services, informal care and treatment over the 6 months of the trial was 16,336
      pounds for placebo, 17,626 pounds for haloperidol and 18,954 pounds for
      risperidone. CONCLUSIONS: There were no significant important benefits conferred
      by treatment with risperidone or haloperidol, and treatment with these drugs was
      not cost-effective. While neuroleptic drugs may be of value in the treatment of
      aggressive behaviour in some patients with intellectual disability, the
      underlying pathology needs to be evaluated before these are given. The specific
      diagnostic indications for such treatment require further investigation.
      Prescription of low doses of neuroleptic drugs in intellectual disability on the
      grounds of greater responsiveness and greater liability to adverse effects also
      needs to be re-examined.

PMID- 19397850
TI  - Introduction to special issue.

PMID- 19397852
TI  - RGD-human serum albumin conjugates as efficient tumor targeting probes.
AB  - Cyclic arginine-glycine-aspartate (RGD) peptides and their derivatives have been
      intensively studied as tumor targeting probes. One major drawback, however, is
      their short blood circulation half-lives, which greatly compromises their
      targeting efficacy. To address this issue, a cyclic peptide, c(RGDyK), and an
      organic dye (IRDye800 or Cy5.5) were covalently conjugated onto human serum
      albumin (HSA). The conjugates were subjected to in vitro cell staining, in vivo
      near-infrared fluorescence (NIRF) imaging, ex vivo NIRF imaging, and histologic
      studies to evaluate their feasibility as tumor imaging probes. As a control, RAD
      peptide was also coupled with HSA and labeled with IRDye800 for in vivo imaging.
      The HSA-RGD-IRDye800 exhibited integrin alpha(v)beta(3)-specific binding in cell
      staining experiment. In vivo NIRF imaging showed higher tumor accumulation and
      tumor to background contrast of HSA-RGD-IRDye800 over RGD-IRDye800. The integrin
      specificity of HSA-RGD-IRDye800 is confirmed by both successful inhibition of
      tumor uptake in the presence of c(RGDyK) and the inability to accumulate in
      integrin-positive tumors by RAD-HSA-IRDye800. Histologic examination revealed
      initial tumor vascular binding and eventually both tumor vasculature and tumor
      cell integrin binding in vivo. In summary, we successfully developed an RGD-based
      protein conjugate with prolonged circulation half-life for NIRF imaging of tumor
      integrin alpha(v)beta(3) expression. The success of this study may be
      generalizable for other peptide-based probes to be conjugated with HSA for
      prolonged tumor contrast and improved pharmacokinetics.

PMID- 19397851
TI  - Molecular imaging of prostate cancer: a concise synopsis.
AB  - Prostate cancer is the most common malignancy in men and continues to be a major
      public health problem. Imaging of prostate cancer remains particularly
      challenging owing to disease heterogeneity. Molecular imaging can provide
      unprecedented opportunities for deciphering the molecular mechanisms that are
      involved in the development and natural progression of prostate cancer from a
      localized process to the hormone-refractory metastatic disease. Such
      understanding will be the key for targeted imaging and therapy and for predicting
      and evaluating treatment response and prognosis. In this article, we review
      briefly the contribution of multimodality molecular imaging methods for the in
      vivo characterization of the pathophysiology of prostate cancer.

PMID- 19397853
TI  - Novel electro-optical coupling technique for magnetic resonance-compatible
      positron emission tomography detectors.
AB  - A new magnetic resonance imaging (MRI)-compatible positron emission tomography
      (PET) detector design is being developed that uses electro-optical coupling to
      bring the amplitude and arrival time information of high-speed PET detector
      scintillation pulses out of an MRI system. The electro-optical coupling
      technology consists of a magnetically insensitive photodetector output signal
      connected to a nonmagnetic vertical cavity surface emitting laser (VCSEL) diode
      that is coupled to a multimode optical fiber. This scheme essentially acts as an
      optical wire with no influence on the MRI system. To test the feasibility of this
      approach, a lutetium-yttrium oxyorthosilicate crystal coupled to a single pixel
      of a solid-state photomultiplier array was placed in coincidence with a lutetium
      oxyorthosilicate crystal coupled to a fast photomultiplier tube with both the new
      nonmagnetic VCSEL coupling and the standard coaxial cable signal transmission
      scheme. No significant change was observed in 511 keV photopeak energy resolution
      and coincidence time resolution. This electro-optical coupling technology enables
      an MRI-compatible PET block detector to have a reduced electromagnetic footprint
      compared with the signal transmission schemes deployed in the current MRI/PET
      designs.

PMID- 19397854
TI  - Dual-modality probes for in vivo molecular imaging.
AB  - Various imaging modalities have been exploited and are successfully employed to
      investigate the anatomic or functional dissemination of tissues in the body.
      However, no single imaging modality allows overall structural, functional, and
      molecular information as each imaging modality has its own unique strengths and
      weaknesses. The combination of two popular imaging modalities that investigates
      the strengths of different methods might offer the prospect of improved
      diagnostic and therapeutic monitoring abilities. To date, only a few hybrid
      systems have become clinically adopted, but there are encouraging signs that the
      new generation of multimodality systems will be undergoing evaluation in the near
      future. On the other hand, significant progress has been made toward the creation
      of dual-modality imaging probes, which can be used as novel tools for future
      multimodality systems. The interdisciplinary research that couples molecular
      imaging science to nanotechnology has generated synergistically integrated novel
      dual-modality imaging probes. These all-in-one probes take full advantage of two
      different imaging modalities and could provide unique information that impacts
      preclinical and, eventually, clinical diagnostics. This review discusses the
      advantages and challenges in developing dual-modality imaging probes and
      summarizes the current state-of-the-art systems with respect to their unique
      design strategies and applications.

PMID- 19397855
TI  - Multimodal imaging of integrin receptor-positive tumors by bioluminescence,
      fluorescence, gamma scintigraphy, and single-photon emission computed tomography
      using a cyclic RGD peptide labeled with a near-infrared fluorescent dye and a
      radionuclide.
AB  - Integrins, particularly the alpha(v)beta(3) heterodimers, play important roles in
      tumor-induced angiogenesis and invasiveness. To image the expression pattern of
      the alpha(v)beta(3) integrin in tumors through a multimodality imaging paradigm,
      we prepared a cyclic RGDyK peptide analogue (LS308) bearing a tetraazamacrocycle
      1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) and a
      lipophilic near-infrared (NIR) fluorescent dye cypate. The alpha(v)beta(3)
      integrin binding affinity and the internalization properties of LS308 mediated by
      the alpha(v)beta(3) integrin in 4t1luc cells were investigated by receptor
      binding assay and fluorescence microscopy, respectively. The in vivo distribution
      of (111)In-labeled LS308 in a 4t1luc tumor-bearing mouse model was studied by
      fluorescence, bioluminescence, planar gamma, and single-photon emission computed
      tomography (SPECT). The results show that LS308 has high affinity for
      alpha(v)beta(3) integrin and internalized preferentially via the alpha(v)beta(3)
      integrin-mediated endocytosis in 4t1luc cells. We also found that LS308
      selectively accumulated in alpha(v)beta(3)-positve tumors in a receptor-specific
      manner and was visualized by the four imaging methods. Whereas the endogenous
      bioluminescence imaging identified the ensemble of the tumor tissue, the
      fluorescence and SPECT methods with the exogenous contrast agent LS308 reported
      the local expression of alpha(v)beta(3) integrin. Thus, the multimodal imaging
      approach could provide important complementary diagnostic information for
      monitoring the efficacy of new antiangiogenic drugs.

PMID- 19397856
TI  - Evaluation of [64Cu]Cu-DOTA and [64Cu]Cu-CB-TE2A chelates for targeted positron
      emission tomography with an alphavbeta6-specific peptide.
AB  - Significant upregulation of the integrin alpha(v)beta(6) has been described as a
      prognostic indicator in several cancers, making it an attractive target for tumor
      imaging. This study compares variants of a PEGylated alpha(v)beta(6)-targeting
      peptide, bearing either an [(18)F]fluorobenzoyl prosthetic group ([(18)F]FBA-PEG
      A20FMDV2) or different [(64)Cu]copper chelators (DOTA-PEG-A20FMDV2, CB-TE2A-PEG
      A20FMDV2). The compounds were evaluated in vitro by enzyme-linked immunosorbent
      assay (against the integrin alpha(v)beta(6) and the closely related integrin
      alpha(v)beta(3)) and by cell labeling (alpha(v)beta(6)-positive
      DX3purobeta6/alpha(v)beta(6)-negative DX3puro) and in vivo using micro-positron
      emission tomography in a mouse model bearing paired DX3purobeta6/Dx3puro
      xenografts. In vitro, all three compounds showed excellent alpha(v)beta(6)
      specific binding (50% inhibitory concentration [IC(50)](alpha(v)beta(6)) = 3 to 6
      nmol/L; IC(50)(alpha(v)beta(3)) > 10 micromol/L). In vivo, they displayed
      comparable, preferential uptake for the alpha(v)beta(6)-expressing xenograft over
      the alpha(v)beta(6)-negative control (> 4:1 ratio at 4 hours postinjection).
      Whereas [(64)Cu]Cu-DOTA-PEG-A20FMDV2 resulted in increased levels of
      radioactivity in the liver, [(64)Cu]Cu-CB-TE2A-PEG-A20FMDV2 did not.
      Significantly, both (64)Cu-labeled tracers showed unexpectedly high and
      persistent levels of radioactivity in the kidneys (> 40% injected dose/g at 4 and
      12 hours postinjection). The findings underscore the potential influence of the
      prosthetic group on targeted in vivo imaging of clinically relevant markers such
      as alpha(v)beta(6). Despite identical targeting peptide moiety and largely equal
      in vitro behavior, both (64)Cu-labeled tracers displayed inferior
      pharmacokinetics, making them in their present form less suitable candidates than
      the (18)F-labeled tracer for in vivo imaging of alpha(v)beta(6).

PMID- 19397857
TI  - Obesity phenotype and intra-abdominal fat responses to regular aerobic exercise.
AB  - AIM: To examine the effects of obesity phenotype on abdominal fat responses to
      regular aerobic exercise. METHOD: Fifty-seven obese men aged 34-70 years were
      divided into two groups based on baseline intra-abdominal fat (IF) area measured
      by computerized tomography: moderate (<200 cm(2)) IF (MIF; n=33, age: 52.9+/-10.6
      [SD] yr, body mass index [BMI]: 29.2+/-3.1 kg/m(2)) or high (>or=200 cm(2)) IF
      (HIF; n=24, age: 53.5+/-9.5 yr, BMI: 30.3+/-3.1 kg/m(2)). The 12-week exercise
      program consisted primarily of aerobic exercise and met 3 days per week for 90
      min per session. Weight, BMI, body composition (by dual-energy X-ray
      absorptiometry), IF and subcutaneous fat (SF) areas were measured before and
      after the program. RESULTS: Regular aerobic exercise reduced weight by 2.3+/-2.2
      kg in MIF and 3.2+/-3.0 kg in HIF. HIF reduced significantly more IF area than
      MIF (15.1+/-26.0 cm(2) in MIF and 43.3+/-41.9 cm(2) in HIF), and the difference
      remained significant after adjusting for baseline fat mass, weight change and
      total energy intake during the 12-week aerobic exercise. CONCLUSION: Exercise
      induced IF reduction may be remarkably influenced by obesity phenotype.

PMID- 19397859
TI  - Control of visually guided saccades in multiple sclerosis: Disruption to higher
      order processes.
AB  - Ocular motor abnormalities are a common feature of multiple sclerosis (MS), with
      more salient deficits reflecting tissue damage within brainstem and cerebellar
      circuits. However, MS may also result in disruption to higher level or cognitive
      control processes governing eye movement, including attentional processes that
      enhance the neural processing of behaviourally relevant information. The
      attentional control of eye movement was investigated in 25 individuals with MS
      and a comparable number of neurologically healthy individuals matched for age and
      IQ. This entailed an evaluation of distractor-related effects on the generation
      of both unpredictable and predictable visually guided saccades, as well as an
      evaluation of the effects of presenting endogenous cues prior to target onset.
      For unpredictable saccades, we revealed an exaggerated distractor effect in MS,
      with saccade latencies prolonged and endpoints less accurate in the presence of a
      visual distractor. Predictable saccades tended to be hypometric for MS patients,
      although we found no significant distractor effects. For endogenously cued
      saccades, we found no group differences in latency following a valid cue, but an
      exaggerated increase in latency following invalid cues for MS patients. MS
      patients also generated a significantly greater proportion of erroneous responses
      to cue stimuli. These ocular motor characteristics demonstrate considerable
      sensitivity with respect to evaluating attentional deficits in MS, evident even
      in the absence of clinical signs of disease.

PMID- 19397858
TI  - The effect of non-visual working memory load on top-down modulation of visual
      processing.
AB  - While a core function of the working memory (WM) system is the active maintenance
      of behaviorally relevant sensory representations, it is also critical that
      distracting stimuli are appropriately ignored. We used functional magnetic
      resonance imaging to examine the role of domain-general WM resources in the top
      down attentional modulation of task-relevant and irrelevant visual
      representations. In our dual-task paradigm, each trial began with the auditory
      presentation of six random (high load) or sequentially ordered (low load) digits.
      Next, two relevant visual stimuli (e.g., faces), presented amongst two temporally
      interspersed visual distractors (e.g., scenes), were to be encoded and maintained
      across a 7-s delay interval, after which memory for the relevant images and
      digits was probed. When taxed by high load digit maintenance, participants
      exhibited impaired performance on the visual WM task and a selective failure to
      attenuate the neural processing of task-irrelevant scene stimuli. The over
      processing of distractor scenes under high load was indexed by elevated encoding
      activity in a scene-selective region-of-interest relative to low load and passive
      viewing control conditions, as well as by improved long-term recognition memory
      for these items. In contrast, the load manipulation did not affect participants'
      ability to upregulate activity in this region when scenes were task-relevant.
      These results highlight the critical role of domain-general WM resources in the
      goal-directed regulation of distractor processing. Moreover, the consequences of
      increased WM load in young adults closely resemble the effects of cognitive aging
      on distractor filtering [Gazzaley, A., Cooney, J. W., Rissman, J., & D'Esposito,
      M. (2005). Top-down suppression deficit underlies working memory impairment in
      normal aging. Nature Neuroscience 8, 1298-1300], suggesting the possibility of a
      common underlying mechanism.

PMID- 19397860
TI  - Cognitive and emotional processing in high novelty seeking associated with the L
      DRD4 genotype.
AB  - The personality trait of novelty seeking (NS) has been associated with the long
      variant of the dopamine D4 receptor (L-DRD4) VNTR polymorphism. This is the first
      study to examine the influence of L-DRD4 polymorphism on some of the cognitive
      (i.e. decision making) and emotional underpinnings of the NS phenotype. One
      hundred and eighteen healthy males grouped in a L-DRD4 (n=24) and a S-DRD4 (n=94)
      group, completed multimodal assessment for personality, planning for problem
      solving and decision making. Two age-matched L-DRD4 and S-DRD4 sub-samples (n=17
      each) entered and completed emotional processing using startle modulation by
      affective pictures. ANOVAs showed that L-DRD4 individuals had higher NS, made
      more risky choices and won less money in the decision making task, but had intact
      planning for problem solving. They also had reduced startle reactivity and late
      startle modulation by both pleasant and unpleasant pictures. Early, attentional
      startle modulation by the affective pictures was intact. NS correlated negatively
      with startle reactivity and performance in the emotional decision task. These
      results suggest that the L-DRD4 polymorphism is associated with high NS and risk
      taking, under-reactivity to unconditioned aversive stimuli, constricted emotional
      responses but preserved attentional processing of emotional stimuli and efficient
      problem solving. These results extend animal evidence on DRD4-mediated control of
      decision making and emotional processing to humans. The proposed role of the NS
      phenotype in human evolution and in disorders of impulsivity is discussed under
      the light of the present findings.

PMID- 19397861
TI  - Frontal lobe involvement in a task of time-based prospective memory.
AB  - Time-based prospective memory (PM) has been found to be negatively affected by
      aging, possibly as a result of declining frontal lobe (FL) function. Despite a
      clear retrospective component to PM tasks, the medial temporal lobes (MTL) are
      thought to play only a secondary role in successful task completion. The present
      study investigated the role of the FLs and MTLs in time-based PM, as well as
      their involvement in clock monitoring, plan generation, and time estimation, each
      of which may play a role in the execution of time-based PM tasks. Based upon
      their scores on composite measures of FL and MTL function, 32 older adults were
      divided into four groups, and were then tested on a time-based laboratory PM
      task. Overall age effects were also assessed and each of the four groups was
      compared to a group of 32 younger adults. High-frontal functioning participants
      demonstrated better prospective memory than low-frontal functioning participants,
      and were not distinguishable from younger adults. Older adults with high-MTL
      scores performed significantly better than those with low-MTL scores, but only if
      they were also high in FL function. FL function, but not MTL function, predicted
      patterns of clock monitoring, quality of plans generated to assist in time-based
      PM performance, and the accuracy of time estimation. Again, on each of these
      measures the performance of the high-frontal group was equivalent to that of the
      younger adults. The results of this study suggest that it is not aging per se
      that disrupts PM performance, but it is instead primarily the diminished frontal
      function seen in a subset of older adults.

PMID- 19397862
TI  - Attention, intention, and strategy in preparatory control.
AB  - The neural mechanisms underlying different forms of preparatory control were
      examined using event-related fMRI. Preparatory brain activation was monitored in
      relation to different types of advance information: (1) random task cues
      indicating which of two possible tasks to perform upon subsequent target
      presentation; (2) task-ambiguous target stimuli; or (3) targets for which the
      correct response could be pre-determined. Three types of activation pattern were
      observed in different brain regions. First, more posterior regions of lateral
      prefrontal cortex (LPFC) and parietal cortex were activated by both advance task
      cues and advance targets, but with increased and more sustained activation for
      the latter. Second, more anterior regions of LPFC and parietal cortex were
      selectively activated by advance targets. Importantly, in these regions
      preparatory activation was not further modulated by the availability of advance
      response information. In contrast, preparatory activation in a third set of brain
      regions, including medial frontal cortex, reflected the utilization of advance
      response information, but by only a subset of participants. These results suggest
      three types of preparatory control: attentional (stimulus-oriented), intentional
      (action-oriented), and a possibly strategic component that might determine inter
      individual differences in response readiness. Notably, the absence of regions
      selectively or even preferentially activated during cue-based preparation argues
      against certain conceptualizations of task-selective attention under cued task
      switching conditions.

PMID- 19397863
TI  - Declarative memory is critical for sustained advantageous complex decision
      making.
AB  - Previous studies have reported conflicting evidence concerning the contribution
      of declarative memory to advantageous decision-making on the Iowa Gambling Task
      (IGT). One study, in which the measurement of psychophysiology during the task
      necessitated a 10-s delay between card selections, found that six participants
      with amnesia due to hippocampal damage failed to develop a preference for
      advantageous decks over disadvantageous decks [Gutbrod, K., Krouzel, C., Hofer,
      H., Muri, R., Perrig, W., & Ptak, R. (2006). Decision-making in amnesia: Do
      advantageous decisions require conscious knowledge of previous behavioural
      choices? Neuropsychologia, 44(8), 1315-1324]. However, a single-case study (where
      psychophysiology was not measured and no delay between card selections occurred)
      showed that an amnesic patient developed normal preference for advantageous decks
      [Turnbull, O. H., & Evans, C. E. (2006). Preserved complex emotion-based learning
      in amnesia. Neuropsychologia, 44(2), 300-306]. We sought to resolve these
      discrepant findings by examining IGT performances in five patients with profound
      amnesia (WMS-III General Memory Index M=63) and bilateral hippocampal damage
      caused by anoxia (n=4) or herpes simplex encephalitis (n=1). In one
      administration of the IGT, psychophysiology measurements were utilized and a 6-s
      delay was interposed between card selections. In a second administration, no
      delay between card selections was interposed. While age-, sex-, and education
      matched healthy comparison participants showed significant learning with a
      gradual preference for advantageous decks in both conditions, amnesic patients,
      irrespective of IGT administration condition and extent of medial temporal lobe
      damage, failed to develop this preference. These findings strongly discount the
      possibility that the delay between card selections explains why amnesic
      participants fail to learn in the IGT, and suggest instead a significant role for
      medial temporal lobe declarative memory systems in the type of complex decision
      making tapped by the IGT.

PMID- 19397865
TI  - Unilateral damage to the right cerebral hemisphere disrupts the apprehension of
      whole faces and their component parts.
AB  - Although most cases of acquired prosopagnosia are accompanied by bilateral brain
      lesions, a number also arise following right unilateral lesions. The prevailing
      consensus is that right hemisphere damage disrupts the configural apprehension of
      faces, which in turn forces a reliance on part-based processing. Here we describe
      a patient who following right hemisphere damage is not only unable to apprehend
      the configural aspects of faces, but is also unable to apprehend their component
      parts when these are presented within a whole, upright face. Intriguingly, the
      patient is able to apprehend face parts when these are presented in isolation,
      within inverted faces, or in unfamiliar, scrambled arrangements. Furthermore, the
      patient can make use of configural information to detect local changes in non
      face stimuli. The findings uncover a hitherto unreported form of impairment
      following right unilateral damage, and raise questions about the role of the left
      hemisphere in processing local information.

PMID- 19397864
TI  - Space-based but not object-based inhibition of return is impaired in Parkinson's
      disease.
AB  - Impairments in certain aspects of attention have frequently been reported in
      Parkinson's disease (PD), including reduced inhibition of return (IOR). Recent
      evidence suggests that IOR can occur when attention is directed at objects or
      locations, but previous investigations of IOR in PD have not systematically
      compared these two frames of reference. The present study compared the
      performance of 18 nondemented patients with PD and 18 normal controls on an IOR
      task with two conditions. In the "object-present" condition, objects surrounded
      the cues and targets so that attention was cued to both a spatial location and to
      a specific object. In the "object-absent" condition, surrounding objects were not
      presented so that attention was cued only to a spatial location. When
      participants had to rely on space-based cues, PD patients demonstrated reduced
      IOR compared to controls. In contrast, when objects were present in the display
      and participants could use object-based cues, PD patients exhibited normal IOR.
      These results suggest that PD patients are impaired in inhibitory aspects of
      space-based attention, but are able to overcome this impairment when their
      attention can be directed at object-based frames of reference. This dissociation
      supports the view that space-based and object-based components of attention
      involve distinct neurocognitive processes.

PMID- 19397866
TI  - Adaptation of eye-movements to simulated hemianopia in reading and visual
      exploration: Transfer or specificity?
AB  - Reading and visual exploration impairments in unilateral homonymous hemianopia
      are well-established clinical phenomena. Spontaneous adaptation of eye-movements
      to the visual field defect leads to improved reading and visual exploration
      performance. Yet, it is still unclear whether oculomotor adaptation to visual
      field loss is task-specific or whether there is a transfer of adaptation-related
      improvements between reading and visual exploration. We therefore simulated
      unilateral homonymous hemianopia in healthy participants and explored the
      specificity with which oculomotor adaptation to this pure visual-sensory
      dysfunction during uninstructed reading or visual exploration practice leads to
      improvements in both abilities. Our findings demonstrate that there is no
      transfer of adaptation-related changes of eye-movements and performance
      improvements between reading and visual exploration. Efficient oculomotor
      adaptation to visual field loss is highly specific and task-dependent.

PMID- 19397867
TI  - Evidence for long-range feedback in target detection: Detection of semantic
      targets modulates activity in early visual areas.
AB  - In a variety of attention and search tasks, single-cell recordings of the primate
      brain have frequently shown an enhancement of responses in early visual areas to
      selected target stimuli. This enhancement is observed only at longer latencies,
      suggesting the possibility that it reflects the action of feedback or return
      signals from upstream processing areas. However, in typical studies, targets are
      specified on the basis of elementary visual features; as these are coded at
      multiple levels of the visual system, it is impossible to determine where
      enhanced target processing begins. Using human functional magnetic resonance
      imaging (fMRI), we demonstrate enhancement of activity in early visual areas even
      when low-level visual information is insufficient for target detection to occur.
      We found enhanced activity in early visual areas to targets defined purely by
      semantic category, suggesting that feedback signals returning from at least as
      far forward as temporal lobe semantic processing can influence visual responses.
      These findings also suggest feedback signaling as a mechanism by which early and
      late brain systems coding for different properties of a target object can
      integrate their activity, allowing for the target object to dominate overall
      processing.

PMID- 19397868
TI  - Cross-sensory gating in schizophrenia and autism spectrum disorder: EEG evidence
      for impaired brain connectivity?
AB  - Autism spectrum disorders (ASD) and schizophrenia are both neurodevelopmental
      disorders that have extensively been associated with impairments in functional
      brain connectivity. Using a cross-sensory P50 suppression paradigm, this study
      investigated low-level audiovisual interactions on cortical EEG activation, which
      provides crucial information about functional integrity of connections between
      brain areas involved in cross-sensory processing in both disorders. Thirteen high
      functioning adult males with ASD, 13 high functioning adult males with
      schizophrenia, and 16 healthy adult males participated in the study. No
      differences in neither auditory nor cross-sensory P50 suppression were found
      between healthy controls and individuals with ASD. In schizophrenia, attenuated
      P50 responses to the first auditory stimulus indicated early auditory processing
      deficits. These results are in accordance with the notion that filtering deficits
      may be secondary to earlier sensory dysfunction. Also, atypical cross-sensory
      suppression was found, which implies that the cognitive impairments seen in
      schizophrenia may be due to deficits in the integrity of connections between
      brain areas involved in low-level cross-sensory processing.

PMID- 19397869
TI  - Visuoperceptual deficits in letter-by-letter reading?
AB  - A longstanding and controversial issue concerns the underlying mechanisms that
      give rise to letter-by-letter (LBL) reading: while some researchers propose a
      prelexical, perceptual basis for the disorder, others postulate a postlexical,
      linguistic source for the problem. To examine the nature of the deficit
      underlying LBL reading, in three experiments, we compare the performance of seven
      LBL readers, matched control participants and one brain-damaged patient, OL, with
      no reading impairment. Experiment 1 revealed that the LBL patients were impaired,
      relative to the controls and to OL, on a same/different matching task using
      checkerboards of black and white squares. Given that the perceptual impairment
      extends beyond abnormalities with alphanumeric stimuli, the findings are
      suggestive of a more general visual processing deficit. This interpretation was
      confirmed in Experiments 2 (matching words and symbol strings) and 3 (visual
      search of letter and symbol targets), which compared the processing of linguistic
      and non-linguistic written stimuli, matched for visual complexity. In both
      experiments, the LBL patients displayed qualitatively similar effects of length
      and left-to-right sequential ordering on linguistic and non-linguistic stimuli.
      Moreover, there was a clear association between the perceptual impairments on
      these tasks and the slope of the reading latency function for the LBL patients.
      Taken together, these findings are consistent with a significant visuoperceptual
      impairment in LBL that adversely affects reading performance as well as
      performance on other non-reading tasks.

PMID- 19397870
TI  - Heterotopagnosia: When I point at parts of your body.
AB  - Heterotopagnosia is the acquired inability of brain-lesioned patients to point at
      someone else's body parts when prompted. The cognitive basis of this disorder is
      unclear. It might result from a biological function deficit critical for
      communication in human beings; alternatively, it could result from the disruption
      of a body representation. Here, we report three patients with heterotopagnosia
      following a recent left parieto-occipital stroke and a previous insular lesion.
      The patients were tested on their ability to name, point out and grasp several
      targets including body parts (own, real others' and figurative others').
      Language, visuo-spatial deficits or any confounding neuropsychological disorders
      were controlled for. We found that the patients erroneously pointed to their own
      body parts when asked to point at someone else's. Strikingly, their ability to
      grasp someone else's body parts was largely unimpaired. The dissociation between
      their grasping and communicative pointing abilities supports the hypothesis that
      heterotopagnosia is a disorder of communicative function conveyed by pointing but
      not by grasping. In addition, pointing performance in our patients varied
      according to the target: the more similar the target was to a real person, the
      worse the patients' pointing performance. We suggest that communicative pointing
      might require a specific representation of the addressee's body and point of
      view, a heterocentric representation. In the patients described here this
      phenomenon resulted from a combined insulo-parietal lesion, which may explain
      why, in contrast to other patients described previously, the heterotopagnosia was
      long-lasting.

PMID- 19397871
TI  - Distractibility with advancing age and Parkinson's disease.
AB  - Focused attention can be compromised by the neurodegenerative processes
      associated with both healthy aging and Parkinson's disease (PD). Deficits in
      ignoring distractors with reflexive or overlearned response links have been
      attributed to impaired inhibition. The current research assessed whether similar
      deficits occur for distractors with recently learned arbitrary response
      associations, for which sensorimotor transformations are far less automatic and
      therefore considerably easier to resist. We used a selective attention task that
      evaluated distractibility and the use of distractor inhibition within the same
      context. The task involved stimuli that were arbitrarily assigned to responses
      based on a rule learned during the testing session. Performance showed that
      distraction increased with both healthy aging and PD. Moreover, these increases
      in distraction were accompanied by decreases in overt evidence of distractor
      inhibition, which appear to reflect at least in part a failure of reactive
      inhibition. Comparison of the deficits in the two groups indicates that the key
      difference reflects severity, rather than distinct symptoms, suggesting that they
      stem from neural changes associated with both aging and PD. These results
      demonstrate that aging- and PD-related hyper-distractibility and impaired
      inhibition during focused attention affect stimuli without prepotent response
      links, which implicates dopaminergic networks in the strategic control of
      arbitrary visuomotor transformations.

PMID- 19397873
TI  - Smooth Brucella strains invade and replicate in human lung  epithelial cells
      without inducing cell death.
AB  - Inhalation is a common route for Brucella infection. We investigated whether
      Brucella species can invade and replicate within alveolar(A549) and bronchial
      (Calu-6 and 16HBE14o-) human epithelial cells. The number of adherent and
      intracellular bacteria was higher for rough strains (Brucella canis and Brucella
      abortus RB51) than for smooth strains (B. abortus 2308 and Brucella suis 1330).
      Only smooth strains exhibited efficient intracellular replication (1.5-3.5 log
      increase at 24 h p.i.). A B. abortus mutant with defective expression of the type
      IV secretion system did not replicate. B. abortus internalization was inhibited
      by specific inhibitors of microfilaments, microtubules and PI3-kinase activity.
      As assessed with fluorescent probes, B. abortus infection did not affect the
      viability of A549 and 16HBE14o- cells, but increased the percentage of injured
      cells (both strains) and dead cells (RB51) in Calu-6 cultures. LDH levels were
      increased in supernatants of Calu-6 and 16HBE14o- cells infected with B. abortus
      RB51, and to a lower extent in Calu-6 infected with B. abortus 2308. No apoptosis
      was detected by TUNEL upon infection with smooth or rough B. abortus. This study
      shows that smooth brucellae can infect and replicate in human respiratory
      epithelial cells inducing minimal or null cytotoxicity.

PMID- 19397874
TI  - Single-point mutations of the M protein of a measles virus variant obtained  from
      a patient with subacute sclerosing panencephalitis critically affect  solubility
      and subcellular localization of the M protein and cell-free virus  production.
AB  - Subacute sclerosing panencephalitis (SSPE) is caused by variants of wild-type
      measles virus (MV). Such MV variants lack almost completely the ability to
      produce cell-free progeny virus. We recently isolated an MV variant that has only
      three amino acid mutations (L165P,L250P and Y282H) in the M protein compared with
      MV field isolates of the same genotype. In the present study, we analyzed the
      significance of these mutations with regard to the characteristics of the M
      protein and progeny virus production. We found that each of the three mutations
      rendered the M protein insoluble in 0.5% Triton X-100 and altered its subcellular
      localization, either when ectopically expressed alone using a plasmid-based
      expression system or when expressed in the context of viral replication.
      Moreover, each of the three mutations markedly, but not completely, impaired the
      ability of MV to produce cell-free progeny virus, with the degree of impairment
      being the same as for all three mutations together. These results suggest the
      possibility that the changes in the solubility and subcellular localization of
      the M protein determine the ability to produce cell-free progeny virus, at least
      to some extent, and play a role in the pathogenicity of variants causing SSPE.

PMID- 19397875
TI  - The hantaviral load in tissues of naturally infected rodents.
AB  - Hantaviruses cause a lifelong and asymptomatic infection in naturally infected
      hosts as well as in experimentally infected rodents. Understanding the ecology
      and pathogenesis of hantaviruses requires an interdisciplinary research approach,
      which links laboratory experiments with results gained from field studies.
      Although several studies report hantavirus persistence and tissue infection
      patterns for experimentally infected rodents, field data is very limited. For
      this reason, the aim of our study was to investigate Puumala, Dobrava and
      Saaremaa virus RNA loads and tissue infection patterns in their natural
      reservoirs. Hantavirus RNA was demonstrated in all tested internal organs and
      blood samples of 14 naturally infected rodent hosts. However, the concentration
      of a specific virus differs depending on the virus, the host and the organ
      tested. Above all, the Dobrava virus showed a considerably higher viral load in
      all internal organs and blood samples of infected Apodemus flavicollis hosts.
      Results obtained in the study support the thesis that virus RNA load reaches its
      peak in the first month after infection, presumably after the virus has spread
      throughout all internal organs. This also implies that recently infected rodents
      are more important for transmission of the virus in the community.

PMID- 19397876
TI  - A rapid and simple method for identifying Mycobacterium tuberculosis W-Beijing
      strains based on detection of a unique mutation in Rv0927c by PCR-SSCP.
AB  - Recently we have found that W-Beijing Mycobacterium tuberculosis strains have a
      unique in-frame trinucleotide (AGC) deletion at position 421 of Rv0927c and a 
      127G-->A mutation in Rv0927c-pstS3 intergenic region. Based on detecting the 421
      trinucleotide deletion of these two mutations which can alter the ssDNA
      conformation more extensively than the other, we developed a PCR-SSCP method for
      rapid identification of W-Beijing strains among non-Beijing strains. Altogether,
      104 clinical isolates were analyzed, including 68 W-Beijing strains and 36 non
      Beijing strains. We found that PCR-SSCP successfully differentiated all the W
      Beijing strains from the non-Beijing strains. In addition, we unexpectedly
      discovered that SDS-PAGE protein gels had better resolving power than
      conventional TBE polyacrylamide gel in detecting the AGC deletion mutation in the
      SSCP analysis.

PMID- 19397877
TI  - Characterization of the serological response to phospholipase D protein of
      Chlamydophila pneumoniae in patients with acute coronary syndromes.
AB  - The purpose of this study was to evaluate the serological response to the
      recombinant phospholipase D protein of Chlamydophila pneumoniae (CpPLD) in
      patients with acute coronary syndromes (ACS) and infected by C. pneumoniae. We
      assessed 100 serum samples from ACS patients and 100 sera from healthy blood
      donors, all categorized by microimmunefluorescence (MIF) into subjects with
      presumptive C. pneumoniae infection or past exposure (only specific IgG), chronic
      infection (presence of specific IgG and IgA), and uninfected, unexposed subjects
      (MIF titer <1:32). None of the MIF-negative sera showed antibodies against CpPLD.
      Among MIF-positive subjects, antibodies to CpPLD were consistently found in sera
      of ACS patients but not in those of healthy subjects, and their titers in ACS
      patients were higher in subjects with both MIF IgG and IgA than in those with MIF
      IgG only. Additionally, we recognized an immunodominant P5 epitope in position
      233-252 aa of the CpPLD protein which strongly reacted with ACS sera. These data
      suggest that CpPLD is a protein potentially implicated in the pathogenesis of C.
      pneumoniae infection. The CpPLD protein and its P5 peptide could be plausible
      antigens for the diagnosis of C. pneumoniae chronic infections in ACS patients.

PMID- 19397878
TI  - CD40 signaling activated by Epstein-Barr virus promotes cell survival and
      proliferation in gastric carcinoma-derived human epithelial cells.
AB  - CD40 signaling plays a critical role in the survival and proliferation of EBV
      infected lymphocytes. Here we show that CD40 is constitutively expressed in the
      human gastric carcinoma-derived cell lines AGS, MKN28, and MKN74, and expression
      of CD40L is induced by in vitro infection with EBV. Blocking the interaction
      between CD40 and CD40L with CD40Ig, a fusion protein of CD40 and IgG, impaired
      proliferation of EBV-infected AGS cells and enhanced their calcium ionophore
      induced apoptosis. These results suggest that CD40 signaling plays a critical
      role in the survival and proliferation of EBV-infected epithelial cells, as well
      as in the virus-infected lymphocytes.

PMID- 19397879
TI  - Heat shock cognate protein 70 controls Borna disease virus replication via
      interaction with the viral non-structural protein X.
AB  - Borna disease virus (BDV) is a non-segmented, negative-sense RNA virus and has
      the property of persistently infecting the cell nucleus. BDV encodes a 10-kDa non
      structural protein, X, which is a negative regulator of viral polymerase activity
      but is essential for virus propagation. Recently, we have demonstrated that
      interaction of X with the viral polymerase cofactor, phosphoprotein (P),
      facilitates translocation of P from the nucleus to the cytoplasm. However, the
      mechanism by which the intracellular localization of X is controlled remains
      unclear. In this report, we demonstrate that BDV X interacts with the 71kDa
      molecular chaperon protein, Hsc70. Immunoprecipitation assays revealed that Hsc70
      associates with the same region of X as P and, interestingly, that expression of
      P interferes competitively with the interaction between X and Hsc70. A heat shock
      experiment revealed that BDV X translocates into the nucleus, dependent upon the
      nuclear accumulation of Hsc70. Furthermore, we show that knockdown of Hsc70 by
      short interfering RNA decreases the nuclear localization of both X and P and
      markedly reduces the expression of viral genomic RNA in persistently infected
      cells. These data indicate that Hsc70 may be involved in viral replication by
      regulating the intracellular distribution of X.

PMID- 19397881
TI  - Simultaneous expression of homologous and heterologous antigens in rough,
      attenuated Brucella melitensis.
AB  - The possibility of expressing a homologous antigen and a heterologous antigen
      simultaneously in an attenuated Brucella melitensis strain was investigated. The
      Brucella wboA gene encoding a mannosyltransferase involved in biosynthesis of
      lipopolysaccharide O-antigen, and the Bacillus anthracis pag gene encoding the
      protective antigen (PA) were cloned into plasmid pBBR4MCS. The resulting plasmid
      was introduced into O-antigen deficient B. melitensis strain WRRP1 to produce
      strain WRSPA. Strain WRSPA produced O-antigen and a series of PA products,
      induced protection in BALB/c mice against challenge with B. melitensis strain
      16M, but failed to protect A/J mice against challenge with B. anthracis Sterne
      strain.

PMID- 19397882
TI  - Immunological's host profile for HPV and Chlamydia trachomatis, a cervical cancer
      cofactor.
AB  - Over 100 different genotypes of human papillomavirus (HPV) have been isolated to
      date, while Chlamydia trachomatis is the most common bacterial sexually
      transmitted pathogen. This review considers evidence that C. trachomatis
      infection became a cofactor for HPV establishment and the development of cervical
      intraepithelial neoplasia.

PMID- 19397883
TI  - Antibacterial activity of human defensins on anaerobic intestinal bacterial
      species: a major role of HBD-3.
AB  - Defensins are natural mucosal antimicrobial peptides and their broad spectrum
      activity against aerobic or facultative anaerobic bacteria has been well
      investigated. The aim of this study was to systematically examine the
      antibacterial activity of the small intestinal Paneth cell derived alpha-defensin
      HD5 and the major colonic beta-defensins HBD-1-3 against strict anaerobic
      intestinal bacteria. The antibacterial activity was assessed with a flow
      cytometric assay employing a membrane potential sensitive dye as marker for loss
      of cell viability. The majority of the tested strains belonging to the dominant
      anaerobe genera of the gut, Bacteroides and Parabacteroides, were only minimally
      affected by the constitutively expressed defensins HD5 and HBD-1. The inducible
      defensin HBD-2 had a limited antibacterial effect, whereas the inducible HBD-3
      exhibited potent activity against most strains. The effect of HBD-3 on
      Bacteroides sp. appeared to be dependent on the presence of oxygen. Bacteroides
      fragilis strains isolated from blood during bacteremia or from extraintestinal
      infections were more resistant to HBD-3 than strains from the physiological gut
      flora. Thus, defensin resistance is not only species- but also strain-specific
      and may be clinically relevant in the host-bacteria interaction influencing
      mucosal translocation and systemic infection.

PMID- 19397884
TI  - Immunogenic and adjuvant properties of Haemophilus ducreyi lipooligosaccharides.
AB  - Haemophilus ducreyi, the chancroid-causing bacterium, produces
      lipooligosaccharides (HdLOS) that comprise 5-11 partially sialylated
      monosaccharides. Subcutaneous immunisation of mice with 5 microg of HdLOS
      purified from H. ducreyi strains 4438 and 7470 induced high levels of anti-HdLOS
      IgG. The antibody responses displayed T-cell-independent features, and were
      dependent upon Toll-like receptor 4/MyD88 signalling pathways as demonstrated
      using knockout mice. The immunogenicity of HdLOS was found to require the intact
      lipid A moiety. The specificity studies of the anti-HdLOS antibodies, as revealed
      by absorption studies, antibody detection in ELISA, and immune thin-layer
      chromatography, indicated that the majority of the anti-LOS antibodies were
      specific for the inner core of the HdLOS. Antibodies to HdLOS failed to inhibit
      LOS induction of TNF-alpha release from human mononuclear cells. The
      adjuvanticity of HdLOS7470 was assessed in BALB/c mice that were immunised with
      bovine serum albumin (BSA) with or without the addition of HdLOS. The addition of
      5 microg HdLOS resulted in a 10-fold increase in the total anti-BSA IgG antibody
      level as estimated by ELISA. The highest increase was noted for IgG2b, which
      contrasted with the predominantly IgG1 subclass response to immunisation with BSA
      alone, indicating an immunomodulatory activity of the HdLOS.

PMID- 19397885
TI  - Marine mammal Brucella isolates with different genomic characteristics display a
      differential response when infecting human macrophages in culture.
AB  - Marine mammal Brucella strains with different genomic characteristics according
      to distribution of IS711 elements in their genomes were analysed for their
      intracellular behaviour in human THP-1 macrophage-like cells. Seven different
      groups of marine mammal strains were identified including a human isolate from
      New Zealand presumably from marine origin. Entry and intracellular survival of
      strains representative of these groups in THP-1 human macrophage-like cells were
      analysed at several times of infection. Three patterns of infection were
      identified. The Brucella strain isolated from the human case from New Zealand,
      and two other groups of strains belonging to B. ceti or B. pinnipedialis were
      able to infect THP-1 macrophage cells to the same extent as the virulent strains
      B. suis 1330 or B. melitensis 16M. Three other groups of strains belonging to B.
      ceti or B. pinnipedialis were able to enter the cells as classical virulent
      strains but were eliminated after 48h. The last group was composed only of
      strains isolated from hooded seals (Cystophora cristata) and was even unable to
      enter and infect THP-1 macrophage cells. Thus, several groups of marine mammal
      Brucella strains appear to be non-infectious for human macrophages.

PMID- 19397886
TI  - Mucosal gene expression profiles following the colonization of immunocompetent
      defined-flora C3H mice with Helicobacter bilis: a prelude to typhlocolitis.
AB  - An aberrant immune response to the commensal microbiota is widely hypothesized to
      contribute to the development of inflammatory bowel disease. Helicobacter bilis
      colonization of defined-flora mice has been shown to trigger host immune
      responses to the commensal flora. However, the magnitude of the effects on
      mucosal homeostasis following colonization with H. bilis has not been determined.
      Using microarray analysis, differential gene expression within the cecal mucosa
      was assessed at 15, 30, or 45 days following H. bilis colonization using
      Affymetrix Genechips. H. bilis colonization induced marked upregulation of genes
      associated with protein metabolism, immune responses, and downregulation of genes
      associated with fatty acid metabolism and detoxification which peaked at 15 days
      postinfection. A set of genes associated with glycoprotein synthesis and
      detoxification including Fut2, B3galt5, Ceacam12, Cyp4b1, and Ugt8a were uniquely
      identified and found to be similarly expressed following the induction of
      typhlocolitis by dextran sodium sulfate or Brachyspira hyodysenteriae. This study
      provides preliminary evidence as to the types of factors or changes in the
      intestinal mucosa that potentially predispose the host to the development of
      typhlocolitis.

PMID- 19397887
TI  - A rapid microwave-assisted derivatization of bacterial metabolome samples for gas
      chromatography/mass spectrometry analysis.
AB  - Analysis of metabolome samples by gas chromatography/mass spectrometry requires a
      comprehensive derivatization method to afford quantitative and qualitative
      information of a complex biological sample. Here we describe an extremely time
      effective microwave-assisted protocol for the commonly used methoxyamine and N
      methyl-N-trimethylsilylfluoracetamide silylation method of primary metabolites.
      Our studies show that microwave irradiation can decrease the sample preparation
      time from approximately 120 min to 6 min without loss of either qualitative or
      quantitative information for the tested synthetic metabolite mixtures and
      microbial-derived metabolome samples collected from Bacillus subtilis and
      Staphylococcus aureus. Comparisons of metabolic fingerprints and selected
      metabolites show no noticeable differences compared with the commonly used
      heating block methods.

PMID- 19397888
TI  - Conjugated eicosapentaenoic acid inhibits human topoisomerase IB with a mechanism
      different from camptothecin.
AB  - Conjugated eicosapentaenoic acid (cEPA) has been found to have antitumor effects
      which has been ascribed to their ability to inhibit DNA topoisomerases and DNA
      polymerases. We here show that cEPA inhibits the catalytic activity of human
      topoisomerase I, but unlike camptothecin it does not stabilize the cleavable
      complex, indicating a different mechanism of action. cEPA inhibits topoisomerase
      by impeding the catalytic cleavage of the DNA substrate as demonstrated using
      specific oligonucleotide substrates, and prevents the stabilization of the
      cleavable complex by camptothecin. Preincubation of the inhibitor with the enzyme
      is required to obtain complete inhibition. Molecular docking simulations indicate
      that the preferred cEPA binding site is proximal to the active site with the
      carboxylic group strongly interacting with the positively charged K443 and K587.
      Taken together the results indicate that cEPA inhibitor does not prevent DNA
      binding but inhibits DNA cleavage, binding in a region close to the topoisomerase
      active site.

PMID- 19397889
TI  - Identification of a specific fucoxanthin-chlorophyll protein in the light
      harvesting complex of photosystem I in the diatom Cyclotella meneghiniana.
AB  - Thylakoids of the diatom Cyclotella meneghiniana were separated by discontinuous
      gradient centrifugation into photosystem (PS) I, PSII, and fucoxanthin
      chlorophyll protein (FCP) fractions. FCPs are homologue to light harvesting
      complexes of higher plants with similar function in e.g. brown algae and diatoms.
      Still, it is unclear if FCP complexes are specifically associated with either PSI
      or PSII, or if FCP complexes function as one antenna for both photosystems.
      However, a trimeric FCP complex, FCPa, and a higher FCP oligomer, FCPb, have been
      described for C. meneghiniana, already. In this study, biochemical and
      spectroscopical evidences are provided that reveal a different subset of
      associated Fcp polypeptides within the isolated photosystem complexes. Whereas
      the PSII associated Fcp antenna resembles FCPa since it contains Fcp2 and Fcp6,
      at least three different Fcp polypeptides are associated with PSI. By re
      solubilisation and a further purification step Fcp polypeptides were partially
      removed from PSI and both fractions were analysed again by biochemical and
      spectroscopical means, as well as by HPLC. Thereby a protein related to Fcp4 and
      a so far undescribed 17 kDa Fcp were found to be strongly coupled to PSI, whereas
      presumably Fcp5, a subunit of the FCPb complex, is only loosely bound to the PSI
      core. Thus, an association of FCPb and PSI is assumed.

PMID- 19397890
TI  - ApcD is necessary for efficient energy transfer from phycobilisomes to
      photosystem I and helps to prevent photoinhibition in the cyanobacterium
      Synechococcus sp. PCC 7002.
AB  - Phycobilisomes (PBS) are the major light-harvesting, protein-pigment complexes in
      cyanobacteria and red algae. PBS absorb and transfer light energy to photosystem
      (PS) II as well as PS I, and the distribution of light energy from PBS to the two
      photosystems is regulated by light conditions through a mechanism known as state
      transitions. In this study the quantum efficiency of excitation energy transfer
      from PBS to PS I in the cyanobacterium Synechococcus sp. PCC 7002 was determined,
      and the results showed that energy transfer from PBS to PS I is extremely
      efficient. The results further demonstrated that energy transfer from PBS to PS I
      occurred directly and that efficient energy transfer was dependent upon the
      allophycocyanin-B alpha subunit, ApcD. In the absence of ApcD, cells were unable
      to perform state transitions and were trapped in state 1. Action spectra showed
      that light energy transfer from PBS to PS I was severely impaired in the absence
      of ApcD. An apcD mutant grew more slowly than the wild type in light
      preferentially absorbed by phycobiliproteins and was more sensitive to high light
      intensity. On the other hand, a mutant lacking ApcF, which is required for
      efficient energy transfer from PBS to PS II, showed greater resistance to high
      light treatment. Therefore, state transitions in cyanobacteria have two roles:
      (1) they regulate light energy distribution between the two photosystems; and (2)
      they help to protect cells from the effects of light energy excess at high light
      intensities.

PMID- 19397891
TI  - Role of acetylcholine receptor domains in ion selectivity.
AB  - The nicotinic acetylcholine receptor (nAChR) is a ligand gated ion channel
      protein, composed of three domains: a transmembrane domain (TM-domain),
      extracellular domain (EC-domain), and intracellular domain (IC-domain). Due to
      its biological importance, much experimental and theoretical research has been
      carried out to explore its mechanisms of gating and selectivity, but there are
      still many unresolved issues, especially on the ion selectivity. Moreover, most
      of the previous theoretical work has concentrated on the TM-domain or EC-domain
      of nAChR, which may be insufficient to understand the entire structure-function
      relation. In this work, we perform molecular dynamics, Brownian dynamics
      simulations and continuum electrostatic calculations to investigate the role of
      different nAChR domains in ion conduction and selectivity. The results show that
      although both the EC and IC domains contain strong negative charges that create
      large cation concentrations at either end of the pore, this alone is not
      sufficient to create the observed cation selectivity and may play a greater role
      in determining the channel conductance. The presence of cations in the wide
      regions of the pore can screen out the protein charge allowing anions to enter,
      meaning that local regions of the TM-domain are most likely responsible for
      discriminating between ions. These new results complement our understanding about
      the ion conduction and selectivity mechanism of nAChR.

PMID- 19397892
TI  - Search for novel neuraminidase inhibitors: Design, synthesis and interaction of
      oseltamivir derivatives with model membrane using docking, NMR and DSC methods.
AB  - As a part of our ongoing program of developing novel influenza virus inhibitors,
      some new derivatives of oseltamivir were prepared by modifying the amino group
      with glycyl, acetyl, benzyl and prolyl moieties. The interactions of these
      derivatives with neuraminidase have been probed by molecular modeling techniques.
      Further, the interaction of these derivatives with model membranes prepared from
      DPPC and the effect on the thermotropic behavior and polymorphism of the bilayers
      have been investigated by multinuclear NMR and DSC methods. Results indicate that
      the glycyl derivative of oseltamivir has the most profound effects on the
      membrane, compared to other derivatives and seems to be the most promising
      derivative for further pharmacological evaluation as a neuraminidase inhibitor.

PMID- 19397893
TI  - Membrane perturbation by the antimicrobial peptide PMAP-23: a fluorescence and
      molecular dynamics study.
AB  - Several bioactive peptides exert their biological function by interacting with
      cellular membranes. Structural data on their location inside lipid bilayers are
      thus essential for a detailed understanding of their mechanism of action. We
      propose here a combined approach in which fluorescence spectroscopy and molecular
      dynamics (MD) simulations were applied to investigate the mechanism of membrane
      perturbation by the antimicrobial peptide PMAP-23. Fluorescence spectra, depth
      dependent quenching experiments, and peptide-translocation assays were employed
      to determine the location of the peptide inside the membrane. MD simulations were
      performed starting from a random mixture of water, lipids and peptide, and
      following the spontaneous self-assembly of the bilayer. Both experimental and
      theoretical data indicated a peptide location just below the polar headgroups of
      the membrane, with an orientation essentially parallel to the bilayer plane.
      These findings, together with experimental results on peptide-induced leakage
      from large and giant vesicles, lipid flip-flop and peptide exchange between
      vesicles, support a mechanism of action consistent with the "carpet" model.
      Furthermore, the atomic detail provided by the simulations suggested the
      occurrence of an additional, more specific and novel mechanism of bilayer
      destabilization by PMAP-23, involving the unusual insertion of charged side
      chains into the hydrophobic core of the membrane.

PMID- 19397894
TI  - Leucine-rich repeat kinase 2 mutants I2020T and G2019S exhibit altered kinase
      inhibitor sensitivity.
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2) are a frequent cause of late
      onset autosomal dominant Parkinson's disease (PD). Some disease-associated
      mutations directly affect LRRK2 kinase activity and inhibition of LRRK2 is viewed
      as a potential therapeutic treatment for PD. We demonstrate by both binding and
      enzymatic assays that alterations in the kinase activity of the PD-associated
      mutants I2020T and G2019S are due in part to altered ATP affinity. In binding
      assays, G2019S and I2020T have approximately 2-fold lower and 6-fold higher ATP
      affinity, respectively, than wild-type LRRK2. Furthermore, using an in vitro
      kinase activity assay, we demonstrate that at ATP concentrations close to
      cellular levels (1 mM) I2020T is approximately 10-fold more resistant to ATP
      competitive kinase inhibitors than wild-type whereas G2019S is 1.6-fold more
      sensitive. These results predict that LRRK2 status may impact kinase inhibitor
      potencies in vivo or in cellular models.

PMID- 19397895
TI  - Resveratrol enhances ultraviolet B-induced cell death through nuclear factor
      kappaB pathway in human epidermoid carcinoma A431 cells.
AB  - Resveratrol has been reported to suppress cancer progression in several in vivo
      and in vitro models, whereas ultraviolet B (UVB), a major risk for skin cancer,
      is known to induce cell death in cancerous cells. Here, we investigated whether
      resveratrol can sensitize A431 human epidermoid carcinoma cells to UVB-induced
      cell death. We examined the combined effect of UVB (30 mJ/cm(2)) and resveratrol
      (60 microM) on A431 cells. Exposure of A431 carcinoma cells to UVB radiation or
      resveratrol can inhibit cell proliferation and induce apoptosis. However, the
      combination of resveratrol and UVB exposure was associated with increased
      proliferation inhibition of A431 cells compared with either agent alone.
      Furthermore, results showed that resveratrol and UVB treatment of A431 cells
      disrupted the nuclear factor-kappaB (NF-kappaB) pathway by blocking
      phosphorylation of serine 536 and inactivating NF-kappaB and subsequent
      degradation of IkappaBalpha, which regulates the expression of survivin.
      Resveratrol and UVB treatment also decreased the phosphorylation of tyrosine 701
      of the important transcription factor signal transducer activator of
      transcription (STAT1), which in turn inhibited translocation of phospho-STAT1 to
      the nucleus. Moreover, resveratrol/UVB also inhibited the metastatic protein
      LIMK1, which reduced the motility of A431 cells. In conclusion, our study
      demonstrates that the combination of resveratrol and UVB act synergistically
      against skin cancer cells. Thus, resveratrol is a potential chemotherapeutic
      agent against skin carcinogenesis.

PMID- 19397896
TI  - Structural biology of human cannabinoid receptor-2 helix 6 in membrane-mimetic
      environments.
AB  - We detail the structure and dynamics of a synthetic peptide corresponding to
      transmembrane helix 6 (TMH6) of human cannabinoid receptor-2 (hCB2) in
      biomembrane-mimetic environments. The peptide's NMR structural biology is
      characterized by two alpha-helical domains bridged by a flexible, nonhelical
      hinge region containing a highly-conserved CWFP motif with an environmentally
      sensitive, Pro-based conformational switch. Buried within the peptide's flexible
      region, W(258) may hydrogen-bond with L(255) to help stabilize the Pro-kinked
      hCB2 TMH6 structure and position C(257) advantageously for interaction with
      agonist ligands. These characteristics of hCB2 TMH6 are potential structural
      features of ligand-induced hCB2 activation in vivo.

PMID- 19397897
TI  - Ascorbic acid conversion to erythroascorbic acid, mediated by ubiquitin.
AB  - We recently identified a microbial conversion of L-ascorbic acid (AsA) to L
      erythroascorbic acid (eAsA), a five-carbon analog of AsA. In this paper, we show
      that ubiquitin plays a crucial role in this process. Based on an assay that
      determined AsA decomposition, we purified proteins that had N-terminal amino acid
      sequences identical to that of yeast ubiquitin. Purified ubiquitin facilitated
      decompositions of AsA and dehydro-AsA, accompanying a partial conversion to eAsA
      through C1-elimination. Acetylation or limited hydrolysis of ubiquitin abolished
      its activity. A mutant ubiquitin, with Lys6 replaced by Arg, completely lost
      activity, whereas a mutant, with six other Lys residues (positions at 11, 27, 29,
      33, 48 and 63) substituted by Arg, retained activity. Thus, Lys6, which locates
      in close proximity to His68, is crucial for ubiquitin activity in the AsA
      conversion to eAsA.

PMID- 19397898
TI  - A morphologic study of Fluorogold labeled tensor tympani motoneurons in mice.
AB  - The tensor tympani is one of two middle ear muscles that regulates the
      transmission of sound through the middle ear. Contraction of the tensor tympani
      in response to both auditory and non-auditory stimulation is mediated by the
      tensor tympani motoneurons (TTMNs). There are interesting differences among
      species in the acoustic thresholds for contraction of the middle ear muscles,
      which may be a reflection of underlying anatomical differences such as the number
      of TTMNs. However anatomical data for mice are lacking, even though the mouse is
      becoming the most common animal model for auditory and neuroscience research. We
      investigated the number and morphology of TTMNs in mice using Fluorogold, a
      retrograde neuronal tracer. After injections of Fluorogold into the tensor
      tympani muscle, a column of labeled TTMNs was identified ventro-lateral to the
      ipsilateral trigeminal nucleus. The labeled TTMNs were classified according to
      their morphological characteristics into three subtypes: "octopus-like",
      "fusiform" and "stellate", suggesting underlying differences in function. All
      three subtypes formed sparsely branched and radiating dendrites, some longer than
      600 microm. Dendrites were longest and most numerous in the dorso-medial
      direction. In 18 cases, the mean number of mouse TTMNs was 51; the largest
      numbers were 70, 74 and 90 (n=3 injections). The mean size of mouse TTMNs was
      13.0 microm (minor axis) and 23.5 microm (major axis). Compared with studies of
      TTMNs in larger species (cats and rats), mouse TTMNs are both fewer in number and
      smaller in size.

PMID- 19397899
TI  - New ectopic vestibular hair cell-like cells induced by Math1 gene transfer in
      postnatal rats.
AB  - Overexpression of Math1 has been demonstrated to induce robust ectopic new hair
      cells in greater epithelial ridge (GER) and lesser epithelial ridge (LER) of the
      postnatal rats' cochlear in vitro. In spite of the similarities between cochlear
      and vestibular epithelia in origin and structure, no similar results have been
      reported in the non-sensory region of vestibular epithelia in vitro. In the
      study, the adenoviral vectors inserted with Math1 gene were constructed to
      examine their effect on vestibular epithelia in postnatal rats. In vivo, the
      adenovirus vectors administered in vestibular perilymphatic or endolymphatic
      space, their transduction efficiency and other indexes are different. We set up a
      culture construction to simulate and show the differences. In the study, we also
      developed a new dissection protocol to be quick to harvest the whole maculae and
      cristae. The new ectopic vestibular hair cell-like cells induced by
      overexpression of Math1, were found to appear in the non-sensory region of the
      postnatal rats' vestibular epithelia as observed in the cochlear, and the number
      of the new cells was different when a different virus administration was
      simulated in vestibular perilymphatic or endolymphatic space, suggesting that the
      cells found could have the capability to differentiate into new hair cells. Our
      study might pave the way for further in vivo studies on vestibular Math1
      adenoviral vector gene transfer.

PMID- 19397900
TI  - Distinguishing the processing of gestures from signs in deaf individuals: an fMRI
      study.
AB  - Manual gestures occur on a continuum from co-speech gesticulations to
      conventionalized emblems to language signs. Our goal in the present study was to
      understand the neural bases of the processing of gestures along such a continuum.
      We studied four types of gestures, varying along linguistic and semantic
      dimensions: linguistic and meaningful American Sign Language (ASL), non
      meaningful pseudo-ASL, meaningful emblematic, and nonlinguistic, non-meaningful
      made-up gestures. Pre-lingually deaf, native signers of ASL participated in the
      fMRI study and performed two tasks while viewing videos of the gestures: a visuo
      spatial (identity) discrimination task and a category discrimination task. We
      found that the categorization task activated left ventral middle and inferior
      frontal gyrus, among other regions, to a greater extent compared to the visual
      discrimination task, supporting the idea of semantic-level processing of the
      gestures. The reverse contrast resulted in enhanced activity of bilateral
      intraparietal sulcus, supporting the idea of featural-level processing (analogous
      to phonological-level processing of speech sounds) of the gestures. Regardless of
      the task, we found that brain activation patterns for the nonlinguistic, non
      meaningful gestures were the most different compared to the ASL gestures. The
      activation patterns for the emblems were most similar to those of the ASL
      gestures and those of the pseudo-ASL were most similar to the nonlinguistic, non
      meaningful gestures. The fMRI results provide partial support for the
      conceptualization of different gestures as belonging to a continuum and the
      variance in the fMRI results was best explained by differences in the processing
      of gestures along the semantic dimension.

PMID- 19397901
TI  - Glycolaldehyde induces fibrinogen post-translational modification, delay in
      clotting and resistance to enzymatic digestion.
AB  - Glycolaldehyde (GA) is a highly reactive aldehyde that can be generated during
      inflammation and hyperglycemia. It can react with arginine and lysine residues
      impairing protein function. As inflammation and diabetes present haemostatic
      dysfunction, we hypothesized that GA could participate in this process. The aim
      of this study was to investigate if plasma incubated in the presence of GA
      presents alteration in the coagulation process. We also aimed to evaluate the
      role of fibrinogen in GA-induced haemostatic dysfunction. For this purpose,
      plasma and fibrinogen were each incubated separately, either in the presence or
      absence of 1 mM GA for 8 and 4 h, respectively. After that, plasma coagulation
      and fibrin polymerization kinetics were recorded, as well as the kinetic of
      plasma clot digestion and fibrinolysis protein carbonylation was quantified. An
      SDS-PAGE was run to check the presence of cross-linking between fibrinogen
      chains. GA induced a delay in plasma coagulation and in fibrin polymerization.
      Maximum absorbance decreased after GA treatment, indicating the generation of
      thinner fibers. Fibrin generated after complete coagulation showed resistance to
      enzymatic digestion, which could be related to the generation of thinner fibers.
      Protein carbonylation also increased after GA treatment. All parameters could be
      reversed with AMG (a carbonyl trap) co-treatment. The data presented herein
      indicate that GA causes post-translational modification of lysine and arginine
      residues, which are central to many events involving fibrinogen to fibrin
      conversion, as well as to fibrinolysis. These modifications lead to the
      generation of persistent clots and may contribute to mortality seen in
      pathologies such diabetes and sepsis.

PMID- 19397902
TI  - Effects of frequency and power of ultrasound on the size reduction of liposome.
AB  - The solutions of liposome made of l-alpha-dilauroyl phosphatidylcholine are
      sonicated at various powers and frequencies (43-480kHz), and the resultant change
      in the size of liposome is measured by the dynamic light scattering method. The
      ultrasonic power dissipated into the solution is determined by the calorimetric
      method in order to compare the effects of ultrasound of different frequencies.
      The faster reduction of the mean size of liposome is achieved at the lower
      frequency. Comparing at the same frequency and total energy, short-time
      irradiation of strong ultrasound is more efficient than long-time irradiation of
      weak ultrasound. These results indicate that the small number of cavitation
      events with stronger physical disturbance on liposome can reduce the size of the
      liposome more efficiently than the large number of cavitation events with weaker
      disturbance.

PMID- 19397903
TI  - Decreased ratio of high-molecular-weight to total adiponectin is associated with
      angiographic coronary atherosclerosis severity but not restenosis.
AB  - BACKGROUND: Adiponectin is thought to protect against atherosclerosis and its
      expression is decreased in metabolic syndrome and diabetes mellitus. Adiponectin
      has a high-molecular-weight (HMW) multimer structure in the blood. We determined
      whether circulating HMW adiponectin, total adiponectin, or their ratio predicts
      baseline angiographic coronary artery disease (CAD) severity and restenosis after
      percutaneous coronary intervention (PCI). METHODS: Patients with stable angina
      pectoris who underwent PCI for a de novo lesion and had angiographic follow-up at
      our hospital were retrospectively enrolled. The study patients were grouped as
      moderate (N=68) or severe (N=63) coronary atherosclerosis by the baseline median
      Gensini severity score (moderate<22, severe> or =22). RESULTS: Univariate
      analysis showed that subjects in the severe CAD group had a lower HMW/total
      adiponectin ratio (0.32+/-0.19 vs. 0.37+/-0.16, p=0.024) while the absolute value
      of HMW adiponectin (2.17+/-2.05 vs. 2.27+/-2.07 microg/ml, p=0.389) and total
      adiponectin (5.97+/-3.12 vs. 5.76+/-2.91 microg/ml, p=0.807) were similar between
      the severe and moderate CAD groups. In a multivariate binary logistic regression
      model, a higher serum HMW/total adiponectin ratio (odds ratio 0.058, p=0.018) was
      negatively, while hypercholesterolemia (OR 2.475, p=0.029) was positively
      associated with coronary atherosclerosis disease severity. In terms of restenosis
      after PCI (mean follow-up at 12+/-13 months), HMW adiponectin, total adiponectin
      and their ratio were similar between restenotic (N=91) and non-restenotic groups
      (N=40). CONCLUSIONS: A decreased ratio of circulating HMW adiponectin to total
      adiponectin is associated with angiographic disease severity but not restenosis
      in CAD patients undergoing PCI.

PMID- 19397904
TI  - Effect of chilling and cryopreservation on expression of Pax genes in zebrafish
      (Danio rerio) embryos and blastomeres.
AB  - Cryopreservation is now common practice in the fields of aquaculture,
      conservation and biomedicine. However, there is a lack of information on the
      effect of chilling and cryopreservation at the molecular level. In the present
      study, we used real-time RT-PCR analysis to determine the effect of chilling and
      cryopreservation on expression of Pax2a, Pax2b, Pax5 and Pax8 which constitute
      one subgroup of the Pax gene family. As intact embryos of zebrafish have not yet
      been successfully cryopreserved, we have used two alternatives: chilling of
      intact embryos and cryopreservation of isolated blastomeres. Cryopreservation was
      found to affect the normal pattern of gene expression in zebrafish embryonic
      blastomeres. The trends, profile changes, in expression of Pax2a and Pax5
      occurred to a lesser extent in frozen-thawed blastomeres than in fresh
      blastomeres whilst the opposite was true for Pax8. The trends in expression of
      Pax2b were delayed in frozen-thawed blastomeres compared to fresh blastomeres.
      Cryopreservation can therefore disrupt normal gene expression patterns in
      zebrafish embryonic blastomeres which could have a detrimental effect on embryo
      development.

PMID- 19397905
TI  - Apc1 is required for maintenance of local brain organizers and dorsal midbrain
      survival.
AB  - The tumor suppressor Apc1 is an intracellular antagonist of the Wnt/beta-catenin
      pathway, which is vital for induction and patterning of the early vertebrate
      brain. However, its role in later brain development is less clear. Here, we
      examined the mechanisms underlying effects of an Apc1 zygotic-effect mutation on
      late brain development in zebrafish. Apc1 is required for maintenance of
      established brain subdivisions and control of local organizers such as the
      isthmic organizer (IsO). Caudal expansion of Fgf8 from IsO into the cerebellum is
      accompanied by hyperproliferation and abnormal cerebellar morphogenesis. Loss of
      apc1 results in reduced proliferation and apoptosis in the dorsal midbrain.
      Mosaic analysis shows that Apc is required cell-autonomously for maintenance of
      dorsal midbrain cell fate. The tectal phenotype occurs independently of Fgf8
      mediated IsO function and is predominantly caused by stabilization of beta
      catenin and subsequent hyperactivation of Wnt/beta-catenin signalling, which is
      mainly mediated through LEF1 activity. Chemical activation of the Wnt/beta
      catenin in wild-type embryos during late brain maintenance stages phenocopies the
      IsO and tectal phenotypes of the apc mutants. These data demonstrate that Apc1
      mediated restriction of Wnt/beta-catenin signalling is required for maintenance
      of local organizers and tectal integrity.

PMID- 19397906
TI  - Intrathecal administration of clonidine attenuates spinal neuroimmune activation
      in a rat model of neuropathic pain with existing hyperalgesia.
AB  - Central neuroimmune activation contributes to the initiation and maintenance of
      neuropathic pain after nerve injury. The current study was aimed to examine the
      modulation of neuroimmune activation in the spinal cord by the alpha(2)
      adrenoceptor agonist, clonidine, in a rat model of neuropathic pain induced by
      partial sciatic nerve ligation (PSNL). Animals were randomly assigned into 6
      groups: sham-operation with 20 microg clonidine or saline; and PSNL with
      clonidine (5, 10, and 20 microg) or saline. Fourteen days post-operation, various
      doses of clonidine or saline were injected intrathecally. The paw pressure
      threshold and paw withdrawal latencies were measured before and at 30, 60, 90,
      and 120 min after the injection of clonidine. Glial activation markers such as
      macrophage antigen complex-1 (mac-1) and glial fibrillary acidic protein (GFAP),
      interleukin (IL)-1beta and IL-6, nuclear factor-kappa B (NF-kappaB) activation,
      and p-p38 mitogen-activated protein kinase (MAPK) activation in the lumbar spinal
      cord were determined as well. Administration of clonidine resulted in a dose
      dependent attenuation in PSNL-induced mechanical and thermal hyperalgesia.
      Furthermore, clonidine could markedly inhibit neuroimmune activation
      characterized by glial activation, production of cytokines, NF-kappaB activation
      as well as p38 activation. The antihyperalgesic effect of intrathecal clonidine
      in rats receiving PSNL might partly attribute to the inhibition of neuroimmune
      activation associated with the maintenance of neuropathic pain.

PMID- 19397908
TI  - Clinical issues in considering vagus nerve stimulation for treatment-resistant
      depression.
AB  - This review briefly discusses the clinical and basic science rationale for vagus
      nerve stimulation (VNS) in treatment-resistant depression (TRD). As the number of
      treatment failures for depression increases, the likelihood of achieving
      remission during acute treatment decreases, and the risk of relapse increases
      with the number of treatment failures. Two open trials of adjunctive VNS for TRD
      showed positive acute results and a growing benefit over time. The results of the
      acute randomized controlled trial were not significant for the primary outcome
      (response by HRSD-24), but the secondary measure (IDS-SR-30) was significant for
      VNS. A 12-month nonrandomized comparative analysis of patients receiving
      adjunctive VNS with TRD patients receiving treatment as usual showed significant
      results favoring VNS. Post hoc analyses found that this difference was not
      accounted for baseline differences nor by intercurrent treatment. While VNS is
      well tolerated, the optimal dosing strategies have not been determined nor have
      clinically useful predictors of who will respond to the treatment. Given the
      profound effects of TRD upon the daily lives of patients and that a substantial
      number of VNS patients receive benefit, VNS is a useful option for managing
      patients with TRD.

PMID- 19397907
TI  - (1R, 3S)-(-)-trans-PAT: a novel full-efficacy serotonin 5-HT2C receptor agonist
      with 5-HT2A and 5-HT2B receptor inverse agonist/antagonist activity.
AB  - The serotonin 5-HT(2A), 5-HT(2B), and 5-HT(2C) G protein-coupled receptors signal
      primarily through G alpha(q) to activate phospholipase C (PLC) and formation of
      inositol phosphates (IP) and diacylglycerol. The human 5-HT(2C) receptor,
      expressed exclusively in the central nervous system, is involved in several
      physiological and psychological processes. Development of 5-HT(2C) agonists that
      do not also activate 5-HT(2A) or 5-HT(2B) receptors is challenging because
      transmembrane domain identity is about 75% among 5-HT(2) subtypes. This paper
      reports 5-HT(2) receptor affinity and function of (1R,3S)-(-)-trans-1-phenyl-3
      dimethylamino-1,2,3,4-tetrahydronaphthalene (PAT), a small molecule that produces
      anorexia and weight-loss after peripheral administration to mice. (-)-Trans-PAT
      is a stereoselective full-efficacy agonist at human 5-HT(2C) receptors, plus, it
      is a 5-HT(2A)/5-HT(2B) inverse agonist and competitive antagonist. The K(i) of (
      )-trans-PAT at 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptors is 410, 1200, and 37
      nM, respectively. Functional studies measured activation of PLC/[(3)H]-IP
      formation in clonal cells expressing human 5-HT(2) receptors. At 5-HT(2C)
      receptors, (-)-trans-PAT is an agonist (EC(50) = 20 nM) comparable to serotonin
      in potency and efficacy. At 5-HT(2A) and 5-HT(2B) receptors, (-)-trans-PAT is an
      inverse agonist (IC(50) = 490 and 1,000 nM, respectively) and competitive
      antagonist (K(B) = 460 and 1400 nM, respectively) of serotonin. Experimental
      results are interpreted in light of molecular modeling studies indicating the (-)
      trans-PAT protonated amine can form an ionic bond with D3.32 of 5-HT(2A) and 5
      HT(2C) receptors, but, not with 5-HT(2B) receptors. In addition to probing 5
      HT(2) receptor structure and function, (-)-trans-PAT is a novel lead regarding 5
      HT(2C) agonist/5-HT(2A) inverse agonist drug development for obesity and
      neuropsychiatric disorders.

PMID- 19397909
TI  - Transient receptor potential vanilloid-1 signaling inhibits differentiation and
      activation of human dendritic cells.
AB  - The goal of the current study was to investigate the expression of transient
      receptor potential vanilloid-1 (TRPV1) on human in vitro differentiated monocyte
      derived dendritic cells (DCs) and to dissect the corresponding role of TRPV1
      signaling in DC-specific functions. TRPV1 expression was identified both at the
      protein and gene levels in human DCs. Moreover, the prototypic TRPV1 agonist
      capsaicin specifically (i.e. via TRPV1) and dose-dependently inhibited cytokine
      induced DC differentiation, phagocytosis of bacteria, activation of DCs, and pro
      inflammatory cytokine secretion. These data introduce TRPV1-coupled signaling as
      a novel player in human monocyte-derived DC biology with anti-inflammatory
      actions.

PMID- 19397910
TI  - The impact of PEPC phosphorylation on growth and development of Arabidopsis
      thaliana: molecular and physiological characterization of PEPC kinase mutants.
AB  - Two phosphoenolpyruvate carboxylase (PEPC) kinase genes (PPCk1 and PPCk2) are
      present in the Arabidopsis genome; only PPCk1 is expressed in rosette leaves.
      Homozygous lines of two independent PPCk1 T-DNA-insertional mutants showed very
      little (dln1), or no (csi8) light-induced PEPC phosphorylation and a clear retard
      in growth under our greenhouse conditions. A mass-spectrometry-based analysis
      revealed significant changes in metabolite profiles. However, the anaplerotic
      pathway initiated by PEPC was only moderately altered. These data establish the
      PPCk1 gene product as responsible for leaf PEPC phosphorylation in planta and
      show that the absence of PEPC phosphorylation has pleiotropic consequences on
      plant metabolism.

PMID- 19397911
TI  - Male hosts are responsible for the transmission of a trophically transmitted
      parasite, Pterygodermatites peromysci, to the intermediate host in the absence of
      sex-biased infection.
AB  - Field studies have identified that male-biased infection can lead to increased
      rates of transmission, so we examined the relative importance of host sex on the
      transmission of a trophically transmitted parasite (Pterygodermatites peromysci)
      where there is no sex-biased infection. We experimentally reduced infection
      levels in either male or female white-footed mice (Peromyscus leucopus) on
      independent trapping grids with an anthelmintic and recorded subsequent infection
      levels in the intermediate host, the camel cricket (Ceuthophilus pallidipes). We
      found that anthelmintic treatment significantly reduced the prevalence of
      infection among crickets in both treatment groups compared with the control, and
      at a rate proportional to the number of mice de-wormed, indicating prevalence was
      not affected by the sex of the shedding definitive host. In contrast, parasite
      abundance in crickets was higher on the grids where females were treated compared
      with the grids where males were treated. These findings indicate that male hosts
      contribute disproportionately more infective stages to the environment and may
      therefore be responsible for the majority of parasite transmission even when
      there is no discernable sex-biased infection. We also investigated whether
      variation in nematode length between male and female hosts could account for this
      male-biased infectivity, but found no evidence to support that hypothesis.

PMID- 19397912
TI  - ZZ polyester beads: an efficient and simple method for purifying IgG from mouse
      hybridoma supernatants.
AB  - ZZ polyester beads are polyhydroxyalkanoate granules which display, at high
      density, the ZZ domain of protein A as a fusion protein covalently linked to the
      polyester core. These granules are produced directly, in one step, by recombinant
      E. coli. We have used these granules produced in a one step process to purify
      mouse IgG1, IgG2a and IgG2b from mouse hybridoma supernatants. Purified
      immunoglobulins were analysed by enzyme-linked immonosorbent assay, agarose gel
      electrophoresis and SDS-PAGE. The results showed that the recovery of IgG is 70%
      or greater with a significant degree of purity. ZZ polyester beads hence offer a
      rapid and novel method to purify IgG from mouse hybridoma culture supernatants.
      As a negative control we used culture supernatant from an IgM secreting hybridoma
      and showed that it did not bind to ZZ polyester beads.

PMID- 19397913
TI  - Rosiglitazone-induced heart remodelling is associated with enhanced turnover of
      myofibrillar protein and mTOR activation.
AB  - We investigated cardiac hypertrophy elicited by rosiglitazone treatment at the
      level of protein synthesis/degradation, mTOR, MAPK and AMPK signalling pathways,
      cardiac function and aspects of carbohydrate/lipid metabolism. Hearts of rats
      treated or not with rosiglitazone (15 mg/kg day) for 21 days were evaluated for
      gene expression, protein synthesis, proteasome and calpain activities, signalling
      pathways, and function by echocardiography. Rosiglitazone induced eccentric heart
      hypertrophy associated with increased expression of ANP, BNP, collagen I and III
      and fibronectin, reduced heart rate and increased stroke volume. Rosiglitazone
      robustly increased heart glycogen content ( approximately 400%), an effect
      associated with increases in glycogenin and UDPG-PPL mRNA levels and glucose
      uptake, and a reduction in glycogen phosphorylase expression and activity.
      Cardiac triglyceride content, lipoprotein lipase activity and mRNA levels of
      enzymes involved in fatty acid oxidation were also reduced by the agonist.
      Rosiglitazone-induced cardiac hypertrophy was associated with an increase in
      myofibrillar protein content and turnover (increased synthesis and an enhancement
      of calpain-mediated myofibrillar degradation). In contrast, 26S beta5
      chymotryptic proteasome activity and mRNA levels of 20S beta2 and beta5 and 19S
      RPN 2 proteasome subunits along with the ubiquitin ligases atrogin and CHIP were
      all reduced by rosiglitazone. These morphological and biochemical changes were
      associated with marked activation of the key growth-promoting mTOR signalling
      pathway, whose pharmacological inhibition with rapamycin completely blocked
      cardiac hypertrophy induced by rosiglitazone. The study demonstrates that both
      arms of protein balance are involved in rosiglitazone-induced cardiac
      hypertrophy, and establishes the mTOR pathway as a novel important mediator
      therein.

PMID- 19397914
TI  - Gingival fibroblast inhibits MMP-7: evaluation in an ex vivo aorta model.
AB  - Matrix metalloproteinases (MMP) play a deleterious role in numerous vascular
      diseases. In contrast, gingival matrix remodelling is adequately regulated by the
      gingival fibroblast (GF). Here, we aimed to evaluate the GF activity on MMP-7
      expression and secretion in coculture with aorta rings. We evaluated MMP-7
      transcription and secretion in rabbit aorta rings cultured or not with gingival
      fibroblasts in collagen gels. GF induced an increase of TIMP-1 transcription and
      secretion, followed, similarly to other MMPs, by the formation of TIMP-1/MMP-7
      complexes. There was also a decrease of MMP-7 mRNA by RT-PCR in aorta rings
      cocultured with gingival fibroblasts. Interestingly, in contrast with other MMPs
      (which were not influenced at a transcription level), GF stimulated the release
      of TGF-beta1, which in turn inhibited the transcription and synthesis of MMP-7,
      as shown by neutralizing MMP-7 inhibition due to gingival fibroblast by
      overexpressing decorin (a TGF beta 1 inhibitor) or by silencing TGF beta 1 using
      siRNA. We showed that healing properties of the GF could be transposed to another
      organ, i.e., ex vivo aneurism model, implicating a down-regulation of MMP-7.

PMID- 19397916
TI  - Enhanced detection of visual targets on the hand and familiar tools.
AB  - This study investigated whether or not the simple detection of visual stimuli is
      better when those stimuli are presented on the hand than on other objects, and
      whether or not detection on other objects improves when people are trained to use
      them as tools. Participants performed a speeded visual detection task to targets
      presented on either side of their own left hand, a fake left hand, and a small
      garden rake. They were then trained to use either the fake hand or the rake as a
      tool with their left hand. Participants initially responded faster to stimuli
      projected onto their real hand than to stimuli presented on the fake hand or the
      tool, but they did not respond faster to stimuli on one side of the hand than on
      the other. After training, participants showed better detection of the visual
      stimuli presented on the object that they had been trained to use than they did
      for stimuli presented on the other object. Moreover, participants responded
      faster to stimuli presented on the upper side of the object that they had been
      trained to use than they did to stimuli on the other side. These findings
      demonstrate that an enhanced visual detection can be induced for stimuli
      presented on tools and other inanimate objects with training, suggesting that
      these objects have been incorporated into the body schema.

PMID- 19397915
TI  - Secondary structures for 5' regions of R2 retrotransposon RNAs reveal a novel
      conserved pseudoknot and regions that evolve under different constraints.
AB  - Sequences from the 5' region of R2 retrotransposons of four species of silk moth
      are reported. In Bombyx mori, this region of the R2 messenger RNA contains a
      binding site for R2 protein and mediates interactions critical to R2 element
      insertion into the host genome. A model of secondary structure for a segment of
      this RNA is proposed on the basis of binding to oligonucleotide microarrays,
      chemical mapping, and comparative sequence analysis. Five conserved secondary
      structures are identified, including a novel pseudoknot. There is an apparent
      transition from an entirely RNA structure coding function in most of the 5'
      segment to a protein coding function near the 3' end. This suggests that local
      regions evolved under separate functional constraints (structural, coding, or
      both).

PMID- 19397917
TI  - Analysis of anabolic steroids in hair: time courses in guinea pigs.
AB  - Sensitive, specific, and reproducible methods for the quantitative determination
      of eight anabolic steroids in guinea pig hair have been developed using LC/MS/MS
      and GC/MS/MS. Methyltestosterone, stanozolol, methandienone, nandrolone,
      trenbolone, boldenone, methenolone and DHEA were administered intraperitoneally
      in guinea pigs. After the first injection, black hair segments were collected on
      shaved areas of skin. The analysis of these segments revealed the distribution of
      anabolic steroids in the guinea pig hair. The major components in hair are the
      parent anabolic steroids. The time courses of the concentrations of the steroids
      in hair (except methenolone, which does not deposit in hair) demonstrated that
      the peak concentrations were reached on days 2-4, except stanozolol, which peaked
      on day 10 after administration. The concentrations in hair appeared to be related
      to the physicochemical properties of the drug compound and to the dosage. These
      studies on the distribution of drugs in the hair shaft and on the time course of
      their concentration changes provide information relevant to the optimal time and
      method of collecting hair samples. Such studies also provide basic data that will
      be useful in the application of hair analysis in the control of doping and in the
      interpretation of results.

PMID- 19397919
TI  - Development of an analytical method for the unambiguous structure elucidation of
      cyclic peptides with special appliance for hepatotoxic desmethylated
      microcystins.
AB  - The periodical occurrence of harmful algal blooms (HABs) in freshwater lakes
      requires the determination of potential cyanobacterial toxins, especially
      microcystins (MCs). On demand of an adequate risk assessment, the high diversity
      of these hepatotoxic cyclic heptapeptides implicates the need of an unambiguous
      detection of their specific structural variants. Therefore, LC-MS and LC-MS/MS
      methods are the approaches of choice for determination of MCs. In contrast, even
      tandem mass spectromic fragmentation patterns are not even sufficient in any kind
      of structural determination requirements, whereas NMR methods require very high
      amounts of MCs. In this study, we present a novel method for chromatographic
      separation of desmethylated microcystins (dm-MCs). Based on the isolation of the
      specific structural variants using semi-preparative HPLC, a method was developed
      for the structure elucidation of cyclic peptides with special appliance for the
      determination of dm-MCs via analysis of the specific amino acid composition after
      peptide hydrolysis followed by stereospecific detection of the amino acids and
      resulting keto acids. On the basis of this method it is demonstrated that dm-MC
      RR with the structure [Dha(7)]MC-RR represented the major compound in the
      microcystin pattern of Microcystis aeruginosa bloom events in 2005 and 2006 in
      Lake Senftenberg, Germany.

PMID- 19397920
TI  - The effects of iodine on kidney bean starch: films and pasting properties.
AB  - In the present study the effect of iodine on the structural characteristics (by
      infrared spectroscopy and X-ray) of films made from kidney bean starch was
      evaluated. The pasting properties as affected by iodine and glycerol were also
      evaluated. Kidney bean starch showed C-type (mixture of A- and B-type)
      crystalline structure, the conversion of starch into films resulted into
      reduction in intensity of diffractograms. The starch powder FTIR spectra had
      peaks centered at 1020 and 995 cm(-1) with a higher intensity at 1020 cm(-1),
      which is consistent with a partially crystalline material since fully crystalline
      material show similar intensity peaks centered around 1020 and 1006 cm(-1). Films
      without iodine showed one main peak centered around 1000 cm(-1) consistent with a
      disordered state similar to that in gelatinized starch. Iodine addition gradually
      increased the intensity of the bands around 1020 cm(-1) consistent with the
      formation of more ordered conformation similar to that in the crystalline
      material. Iodine encourages the formation of helical structures, however, the
      formation of crystalline material cannot be inferred. The increasing amounts of
      iodine up to 0.33% level progressively increased the peak-, through- and
      breakdown-viscosity. Iodine beyond 0.33% level gradually decreased peak-, trough
      , breakdown- and setback-viscosity. Pasting temperature gradually increased with
      the increase in iodine.

PMID- 19397918
TI  - Prostaglandin E2 released from activated microglia enhances astrocyte
      proliferation in vitro.
AB  - Microglial activation has been implicated in many astrogliosis-related
      pathological conditions including astroglioma; however, the detailed mechanism is
      not clear. In this study, we used primary enriched microglia and astrocyte
      cultures to determine the role of microglial prostaglandin E(2) (PGE(2)) in the
      proliferation of astrocytes. The proliferation of astrocytes was measured by BrdU
      incorporation. The level of PGE(2) was measured by ELISA method. Pharmacological
      inhibition or genetic ablation of COX-2 in microglia were also applied in this
      study. We found that proliferation of astrocytes increased following
      lipopolysaccharide (LPS) treatment in the presence of microglia. Furthermore,
      increased proliferation of astrocytes was observed in the presence of conditioned
      media from LPS-treated microglia. The potential involvement of microglial PGE(2)
      in enhanced astrocyte proliferation was suggested by the findings that PGE(2)
      production and COX-2 expression in microglia were increased by LPS treatment. In
      addition, activated microglia-induced increases in astrocyte proliferation were
      blocked by the PGE(2) antagonist AH6809, COX-2 selective inhibitor DuP-697 or by
      genetic knockout of microglial COX-2. These findings were further supported by
      the finding that addition of PGE(2) to the media significantly induced astrocyte
      proliferation. These results indicate that microglial PGE(2) plays an important
      role in astrocyte proliferation, identifying PGE(2) as a key neuroinflammatory
      molecule that triggers the pathological response related to uncontrollable
      astrocyte proliferation. These findings are important in elucidating the role of
      activated microglia and PGE(2) in astrocyte proliferation and in suggesting a
      potential avenue in the use of anti-inflammatory agents for the therapy of
      astroglioma.

PMID- 19397921
TI  - Effects of immobilization onto aluminum hydroxide particles on the thermally
      induced conformational behavior of three model proteins.
AB  - Although the thermal unfolding/aggregation behavior of proteins in solution has
      been extensively studied, little is known about proteins immobilized on the
      surface of nanoparticles and other solid-phase materials. In this study we
      carefully monitor and analyze the thermal denaturation process of three model
      proteins adsorbed onto aluminum hydroxide as a function of temperature by FT-IR
      spectroscopy. The results reveal that the proteins immobilized onto aluminum
      hydroxide retain their native conformation at lower temperatures (<45 degrees C).
      Upon thermal denaturation, the structural transition between the native and
      denatured states is very similar, in terms of disappearance of the major native
      secondary structural elements, between the proteins adsorbed onto aluminum
      hydroxide adjuvant and in solution. This result suggests that the thermal
      stability of proteins is not significantly affected, or marginally affected at
      most, by the adsorption onto aluminum hydroxide adjuvant, considering a 5 degrees
      C temperature interval used for data collection. However, the adsorption rate and
      crowding of proteins on aluminum hydroxide particles have a profound effect on
      the aggregation behavior of the proteins, hydrogen bonding strength of
      intermolecular beta-sheet aggregates and conformation of intermediate states.

PMID- 19397922
TI  - Structure of amyloid fibrils of hen egg white lysozyme studied by microbeam X-ray
      diffraction.
AB  - Structure of spherical aggregates formed by hen egg white lysozyme (HEWL) was
      studied with microbeam X-ray diffraction. Aggregates with a diameter of 50-100
      microm were formed after incubation of HEWL at pH 1.6 and 60 degrees C up to 60
      days. The scattering from the aggregate in solution showed a marked symmetry
      demonstrating it as a spherulite. A reflection at 1/0.46 nm(-1) along the fiber
      axis showed the presence of beta-sheets along the fiber. There were strong
      equatorial reflections at 1/2.4 and 1/1.2 nm(-1). The similarities to other
      amyloid fibers suggest that molecules are planar in the direction perpendicular
      to the fiber axis and beta-strands are making hydrogen bonds to neighboring
      molecules.

PMID- 19397923
TI  - Chemical modification and antitumor activities of two polysaccharide-protein
      complexes from Pleurotus tuber-regium.
AB  - Two water-soluble polysaccharide-protein complexes, extracted from Pleurotus
      tuber-regium sclerotia, were modified chemically to obtain their sulfated and
      carboxymethylated derivatives. While C6 position of glucan was fully substituted,
      C2, C3, and C4 were only partially substituted by sulfate groups. C3, C4, and C6
      position of glucan were partially substituted during the carboxymethylation.
      Chain conformation and antitumor activity of the native samples and their
      derivatives were studied. The native samples and derivatives existed in sphere
      conformation, and showed potent in vitro antitumor activities. Water-solubility
      and introduction of ionic groups played important roles in enhancing the
      antitumor activities of the polysaccharide-protein complexes.

PMID- 19397924
TI  - Interaction and complex formation between catalase and cationic polyelectrolytes:
      chitosan and Eudragit E100.
AB  - Interactions between catalase and the cationic polyelectrolytes: chitosan and
      Eudragit E100 have been investigated owing to their scientific and technological
      importance. These interactions have been characterized by turbidimetry, circular
      dichroism and fluorescence spectroscopy. It was found that the catalase
      conformation does not change significantly during the chain entanglements between
      the protein and the polyelectrolytes. The effects of pH, ionic strength and
      anions which modify the water structure were evaluated on the polymer-protein
      complex formation. A net coulombic interaction force between them was found since
      the insoluble complex formation decreased after the NaCl addition. Both polymers
      were found to precipitate around 80% of the protein in solution. No modification
      of the tertiary and secondary protein structure or the enzymatic activity was
      observed when the precipitate was dissolved by changing the pH of the medium.
      Chitosan and Eudragit E100 proved to be a useful framework to isolate catalase or
      proteins with a slightly acid isoelectrical pH by means of precipitation.

PMID- 19397925
TI  - Binding and inhibition in episodic memory-cognitive, emotional, and neural
      processes.
AB  - The goal-directed use of human memory requires that irrelevant or unpleasant
      memories are, at least temporarily, reduced in their accessibility and memory for
      more relevant or pleasant information is enhanced, thus making memory more
      efficient. There is evidence that, in memory, inhibitory processes operate to
      serve this function. Results from three experimental paradigms are reviewed in
      which the action of intentionally and unintentionally recruited inhibitory
      processes has been suggested. The findings provide evidence on representational
      preconditions for the action of inhibitory processes, specifying binding
      structures in which inhibitory processes may be triggered and binding structures
      in which inhibitory processes are generally not observed. The findings also
      provide evidence on how inhibition affects memory representations, including
      changes at the memory unit level and changes in the binding between single units.
      Finally, current knowledge on the interplay between inhibition and emotion and on
      possible neural correlates of inhibitory processes is reviewed.

PMID- 19397927
TI  - PCR-based amplification and analysis of specific viral sequences from individual
      plant cells.
AB  - Plant virus diversity and the spatial distribution of viral strains or isolates
      are studied at many different scales: global, regional, local, and even within a
      single host in different organs or tissues. However, one level that has been
      totally lacking at the extremity of this scale is that of the single cell. The
      technical difficulties involved in isolating individual cells from infected
      plants, and the lack of an efficient diagnostic procedure allowing the specific
      detection of viral sequences with no major contamination from other cells, have
      precluded such single cell analysis to date. This paper describes the preparation
      of protoplasts from plants infected with Cauliflower mosaic virus (CaMV), and
      their decontamination and separation using a technique requiring no specialised
      equipment. Efficient single-cell nested-PCR procedures (both standard and high
      resolution-melting) were developed to allow efficient amplification and analysis
      of viral sequences from isolated single cells. Moreover, the specific
      identification of two CaMV variants in different cells demonstrated a very low
      level of cross-contamination. This technique paves the way for the future
      development of numerous applications of broad interest in the study of viral
      diversity and population genetics of plant viruses at the cellular level.

PMID- 19397926
TI  - Ketamine and the next generation of antidepressants with a rapid onset of action.
AB  - Existing treatments for major depressive disorder (MDD) usually take weeks to
      months to achieve their antidepressant effects, and a significant number of
      patients do not have adequate improvement even after months of treatment. In
      addition, increased risk of suicide attempts is a major public health concern
      during the first month of standard antidepressant therapy. Thus, improved
      therapeutics that can exert their antidepressant effects within hours or a few
      days of their administration are urgently needed, as is a better understanding of
      the presumed mechanisms associated with these rapid antidepressant effects. In
      this context, the N-methyl-D-aspartate (NMDA) antagonist ketamine has
      consistently shown antidepressant effects within a few hours of its
      administration. This makes it a valuable research tool to identify biomarkers of
      response in order to develop the next generation of fast-acting antidepressants.
      In this review, we describe clinical, electrophysiological, biochemical, and
      imaging correlates as relevant targets in the study of the antidepressant
      response associated with ketamine, and their implications for the development of
      novel, fast-acting antidepressants. We also review evidence that alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to NMDA throughput may
      represent a convergent mechanism for the rapid antidepressant actions of
      ketamine. Overall, understanding the molecular basis of this work will likely
      lead to the ultimate development of improved therapeutics for MDD.

PMID- 19397928
TI  - Production of polyclonal antibodies against Pelargonium zonate spot virus coat
      protein expressed in Escherichia coli and application for immunodiagnosis.
AB  - Pelargonium zonate spot virus (PZSV) is identified recently in tomato plants in
      the United States. To develop serological diagnostic tools for the detection of
      this virus, the production of good quality antibodies is a necessity. The coat
      protein (CP) gene of a California isolate of PZSV was cloned into a bacterial
      expression vector (pTriEX-4 Ek/LIC). The plasmid pTriEX-4-PZSV-CP was transformed
      into Escherichia coli Rosetta 2(DE3)pLacI and the recombinant PZSV-CP was
      expressed as a fusion protein containing N-terminal hexa-histidine and S tags.
      Expressed PZSV-CP was purified under denaturing conditions by affinity
      chromatography yielding 3mg refolded protein per 200mL of bacterial culture, and
      used as an antigen for raising PZSV-CP antiserum in rabbits. Specificity of the
      antiserum to PZSV was shown by Western blot and ELISA. When used in Western blot
      analysis, the antiserum was able to detect the recombinant protein, the PZSV coat
      protein and PZSV infected plant samples. The antiserum was successfully used in
      indirect-ELISA at dilutions of up to 1:16,000 to detect PZSV in infected leaf
      samples. Direct ELISA was successful only with denatured antigens. This is the
      first report on production of polyclonal antiserum against recombinant coat
      protein of PZSV and its use for detection and diagnosis of virus using
      serological methods.

PMID- 19397929
TI  - Inhibition of HIV-1 replication by long-term treatment with a chimeric RNA
      containing shRNA and TAR decoy RNA.
AB  - Combinatorial therapies for the treatment of HIV-1 infection are effective for
      reducing patient viral loads and slowing the progression to AIDS. Our strategy
      was based on an anti-HIV-1 shRNA vector system in which HIV-1 vif-shRNA was fused
      to a decoy TAR RNA (mini-TAR RNA) to generate vif-shRNA-decoy TAR RNA under the
      control of the human U6 Pol III promoter. Upon expression in human cells, the RNA
      molecule was cleaved into its component parts, which inhibited HIV-1 replication
      in a synergistic manner. This chimeric RNA expressed a dual RNA moiety and
      greatly enhanced the inhibition of HIV-1 replication under the production of
      resistant virus by short interference RNA (siRNA) in long-term culture assays. We
      suggest that this technique provides a practical basis for the application of
      siRNA-based gene therapy in the treatment of HIV/AIDS.

PMID- 19397930
TI  - A reporter cell line for rapid and sensitive evaluation of hepatitis C virus
      infectivity and replication.
AB  - The human pathogen hepatitis C virus (HCV) is associated with chronic liver
      disease. The recent development of the cell culture infectious HCV (HCVcc) system
      has opened up avenues for detailed studies on the life cycle of the virus and its
      interaction with the host cell. Current methods to quantitate virus infectivity
      in cell culture are time-consuming and labor-intensive. This study describes the
      generation of a cell-based secreted alkaline phosphatase (SEAP) reporter assay to
      facilitate in vitro studies of HCV infection and replication. This assay is based
      on a novel reporter cell line stably expressing the enhanced green fluorescent
      protein (EGFP) fused in-frame to the secreted alkaline phosphatase via a
      recognition sequence of the viral NS3/4A serine protease. The SEAP reporter from
      a similar construct has previously been shown to be released from the fusion
      protein and be secreted into the extracellular culture medium following cleavage
      by the viral NS3/4A protease. The reporter cell line enabled rapid and sensitive
      quantification of HCV infection and viral replication in cell culture. The
      utility of this system for investigating virus entry, and for high throughput
      screening of entry inhibitors and other antiviral compounds was demonstrated
      using several inter- and intra-genotypic chimeras of HCV.

PMID- 19397932
TI  - Anxiolytic effects of rapid amygdala kindling, and the influence of early life
      experience in rats.
AB  - The incidence of psychiatric disturbances is elevated in temporal lobe epilepsy
      (TLE) patients. Early life stressful events are believed to have a major impact
      on mental health later in life, and increasing evidence suggests that such
      stresses may also promote a vulnerability to TLE. This study investigated whether
      subjecting rats to early life stress exacerbated mood and cognitive disturbances
      associated with the development of epilepsy. On postnatal days 2-14, rat pups
      were separated from their dams for either 180 min/day (handling and maternal
      separation--HMS180, modelling early life stress) or 15 min/day (control handling
      and maternal separation--HMS15). At 7 weeks, rats were implanted with a bipolar
      electrode into the left amygdala. Following recovery, one group of rats from each
      litter underwent rapid amygdala kindling (RAK) epileptogenesis, while another
      underwent sham kindling. One week following this, rats were subjected to
      behavioural tests assessing anxiety and cognition. HMS180-exposed rats kindled
      faster than HMS15 rats (p<0.0001). RAK induced a potent anxiolytic effect as
      evidenced by increased % time spent in the open arms of the elevated plus maze,
      compared with sham kindled rats (p<0.0001). This anxiolytic effect was also
      observed in the open field task, as evidenced by increased time spent in the
      inner area (p=0.010). Neither RAK nor maternal separation had any effect on
      cognitive function in the Morris water maze. We conclude that maternal separation
      stress accelerates limbic epileptogenesis in adult rats, and that RAK induces
      potent anxiolytic effects that are not influenced by such early life stressful
      events.

PMID- 19397933
TI  - Effects of bilateral lesions in thalamic reticular nucleus and orbitofrontal
      cortex in a T-maze perseverative model produced by 8-OH-DPAT in rats.
AB  - OBJECTIVE: Stereotaxic lesions of the orbitofrontal-thalamic system, specifically
      the thalamic reticular nucleus (TRN), could be helpful to prevent perseverative
      behavior in rats produced by 8-OH-DPAT. METHODS: Fifty rats were conditioned in a
      T-maze to measure the number of perseverations. Habituation was performed on days
      1 and 2, baseline scores were obtained on day 3 and the final test was done on
      day 4 (chemical induction). Group I only received saline solution injection;
      group II was only submitted to 8-OH-DPAT; group III received pharmacological
      treatment with chlorimipramine (CMI) before 8-OH-DPAT administration; group IV
      and group V were submitted to stereotaxic bilateral lesions, one week before T
      maze evaluation, in the TRN and orbitofrontal cortex (OFC), respectively and
      received 8-OH-DPAT administration. RESULTS: No differences between groups were
      found at baseline on day 3 (p<0.05). Significant differences were found between
      days 3 and 4 of evaluation only in group II (p<0.01) and group V (p<0.001).
      Differences between groups on day 4 were significant (p<0.01). CONCLUSIONS: TRN
      lesions were as effective as CMI administration to prevent the 8-OH-DPAT action.
      OFC lesions failed to prevent the perseverative behavior.

PMID- 19397934
TI  - Chronic stress induces dendritic atrophy in the rat medial geniculate nucleus:
      effects on auditory conditioning.
AB  - Chronic stress induces dendritic atrophy in the inferior colliculus (IC, auditory
      mesencephalon) and impairs auditory avoidance conditioning. The aim of this study
      was to determine in Golgi preparations and in cued fear conditioning whether
      stress affects other auditory components, like the thalamic medial geniculate
      nucleus (MG) or the posterior thalamic nucleus (PO), in Sprague-Dawley rats.
      Chronic restraint stress produced a significant dendritic atrophy in the MG
      (stress: 407+/-55 microm; control: 808+/-120 microm; p<0.01) but did not affect
      auditory fear conditioning. The last result was in apparent contrast with the
      fact that stress impairs both the acquisition of auditory avoidance conditioned
      responses and the dendritic structure in two major nuclei of the auditory system.
      In order to analyze this disagreement, we investigated whether the stress-related
      freezing to tone occurring in the fear conditioning protocol corresponded to a
      conditioned or an unconditioned fear response, using changes in tone instead of
      light throughout conditioning trials. Chronic stress significantly enhanced
      visual fear conditioning in stressed animals compared to controls (stress: 58.9+/
      8.42%, control: 23.31+/-8.01%; p<0.05), but this fear enhancement was related to
      unconditioned fear. Conversely, chronic stress did not affect the morphology of
      the PO (subserving both auditory and somatosensory information) or the
      corresponding auditory and somatosensory unconditioned responses (acoustic
      startle response and escape behavior). Our results suggest that the auditory
      conditioned stimulus can be processed in part independently of the IC and MG in
      the stressed animals, and sent to the amygdala via the PO inducing unconditioned
      fear. Comparable alterations could be produced in major depression.

PMID- 19397931
TI  - Prepulse inhibition and genetic mouse models of schizophrenia.
AB  - Mutant mouse models related to schizophrenia have been based primarily on the
      pathophysiology of schizophrenia, the known effects of antipsychotic drugs, and
      candidate genes for schizophrenia. Sensorimotor gating deficits in schizophrenia
      patients, as indexed by measures of prepulse inhibition of startle (PPI), have
      been well characterized and suggested to meet the criteria as a useful
      endophenotype in human genetic studies. PPI refers to the ability of a non
      startling "prepulse" to inhibit responding to the subsequent startling stimulus
      or "pulse." Because of the cross-species nature of PPI, it has been used
      primarily in pharmacological animal models to screen putative antipsychotic
      medications. As techniques in molecular genetics have progressed over the past 15
      years, PPI has emerged as a phenotype used in assessing genetic mouse models of
      relevance to schizophrenia. In this review, we provide a selected overview of the
      use of PPI in mouse models of schizophrenia and discuss the contribution and
      usefulness of PPI as a phenotype in the context of genetic mouse models. To that
      end, we discuss mutant mice generated to address hypotheses regarding the
      pathophysiology of schizophrenia and candidate genes (i.e., hypothesis driven).
      We also briefly discuss the usefulness of PPI in phenotype-driven approaches in
      which a PPI phenotype could lead to "bottom up" approaches of identifying novel
      genes of relevance to PPI (i.e., hypothesis generating).

PMID- 19397935
TI  - Evidence from knockout mice that peptide YY and neuropeptide Y enforce murine
      locomotion, exploration and ingestive behaviour in a circadian cycle- and gender
      dependent manner.
AB  - Peptide YY (PYY) and neuropeptide Y (NPY) have been proposed to participate in
      the control of energy homeostasis. Since these activities show circadian
      variations, we explored the circadian pattern of locomotor, exploratory and
      ingestive behaviour in male and/or female mice with disrupted genes for PYY (PYY
      /-), NPY (NPY-/-) as well as PYY plus NPY (PYY+NPY-/-). The effect of bacterial
      lipopolysaccharide (LPS, 0.1 mg/kg intraperitoneally) on these behaviours was
      also examined. The animals were housed singly in cages fitted with sensors for
      water and food intake and two infrared frames for recording ambulation and
      rearing under a 12 h light/dark cycle for 4 days. Locomotor and exploratory
      behaviour was decreased in female NPY-/- as well as male and female PYY+NPY-/-
      mice during the photo- and scotophase, and in male PYY-/- mice during the
      scotophase. Significant decreases in water and food intake were seen in female
      NPY-/- as well as male and female PYY+NPY-/- mice during the photophase. The
      effect of LPS to attenuate ingestive behaviour during the light and/or dark phase
      was most pronounced in PYY-/- and NPY-/- mice. These findings attest to a
      circadian cycle- and gender-related role of NPY and PYY in the control of
      behaviours that balance energy intake and energy expenditure. Both peptides
      stimulate feeding and drinking to balance the energy demand that they generate by
      enforcing the circadian pattern of locomotion and exploration. In addition, they
      counteract the anorectic and antidipsogenic effects of immune challenge.

PMID- 19397936
TI  - Effects of voluntary running on spatial memory and mature brain-derived
      neurotrophic factor expression in mice hippocampus after status epilepticus.
AB  - Voluntary physical activity improves memory and learning ability in rodents,
      whereas status epilepticus has been associated with memory impairment. Physical
      activity and seizures have been associated with enhanced hippocampal expression
      of BDNF, indicating that this protein may have a dual role in epilepsy. The
      influence of voluntary physical activity on memory and BDNF expression has been
      poorly studied in experimental models of epilepsy. In this paper, we have
      investigated the effect of voluntary physical activity on memory and BDNF
      expression in mice with pilocarpine-induced epilepsy. Male Swiss mice were
      assigned to four experimental groups: pilocarpine sedentary (PS), pilocarpine
      runners (PRs), saline sedentary (SS) and saline runners (SRs). Two days after
      pilocarpine-induced status epilepticus, the affected mice (PR) and their running
      controls (SR) were housed with access to a running wheel for 28 days. After that,
      the spatial memory and the expression of the precursor and mature forms of
      hippocampal BDNF were assessed. PR mice performed better than PS mice in the
      water maze test. In addition, PR mice had a higher amount of mature BDNF (14kDa)
      relative to the total BDNF (14kDa+28kDa+32kDa forms) content when compared with
      PS mice. These results show that voluntary physical activity improved the spatial
      memory and increased the hippocampal content of mature BDNF of mice with
      pilocarpine-induced status epilepticus.

PMID- 19397937
TI  - Bilateral vestibular deafferentation causes deficits in a 5-choice serial
      reaction time task in rats.
AB  - Peripheral lesions of the vestibular system have been associated with spatial
      memory deficits in animals and humans; however, no study to date has investigated
      the effects of such lesions on attention. In this study, we used a 5-choice
      serial reaction time task (5-CSRTT) to determine whether rats with bilateral
      vestibular deafferentation (BVD) had attention deficits at 5 months post-op.
      compared to sham controls. We found that BVD rats took longer than sham animals
      to reach the designated criterion of >70% correct responses (P=0.006), they made
      significantly fewer correct responses (P=0.005), and significantly more incorrect
      responses (P=0.000), while showing no difference in omissions and premature
      responses and a significant decrease in perseverative responses (P=0.03). BVD
      rats also responded with a significantly shorter response latency, whether their
      response was correct (P=0.001) or incorrect (P=0.002), and obtained their reward
      for a correct response more quickly (P=0.000). These results suggest that rats
      with bilateral vestibular loss exhibit deficits on a 5-CSRTT that cannot be
      explained by an inability to respond and that their speed of response is altered.

PMID- 19397939
TI  - Cortical oscillatory activity associated with the perception of illusory and real
      visual contours.
AB  - We used magnetoencephalography (MEG) to examine the nature of oscillatory brain
      rhythms when passively viewing both illusory and real visual contours. Three
      stimuli were employed: a Kanizsa triangle; a Kanizsa triangle with a real
      triangular contour superimposed; and a control figure in which the corner
      elements used to form the Kanizsa triangle were rotated to negate the formation
      of illusory contours. The MEG data were analysed using synthetic aperture
      magnetometry (SAM) to enable the spatial localisation of task-related oscillatory
      power changes within specific frequency bands, and the time-course of activity
      within given locations-of-interest was determined by calculating time-frequency
      plots using a Morlet wavelet transform. In contrast to earlier studies, we did
      not find increases in gamma activity (>30 Hz) to illusory shapes, but instead a
      decrease in 10-30 Hz activity approximately 200 ms after stimulus presentation.
      The reduction in oscillatory activity was primarily evident within extrastriate
      areas, including the lateral occipital complex (LOC). Importantly, this same
      pattern of results was evident for each stimulus type. Our results further
      highlight the importance of the LOC and a network of posterior brain regions in
      processing visual contours, be they illusory or real in nature. The similarity of
      the results for both real and illusory contours, however, leads us to conclude
      that the broadband (<30 Hz) decrease in power we observed is more likely to
      reflect general changes in visual attention than neural computations specific to
      processing visual contours.

PMID- 19397938
TI  - Haemodynamic reactions to acute psychological stress and smoking status in a
      large community sample.
AB  - Exaggerated haemodynamic reactions to acute psychological stress have been
      implicated in a number of adverse health outcomes. This study examined, in a
      large community sample, the cross-sectional associations between haemodynamic
      reactivity and self-reported smoking status. Blood pressure and heart rate were
      measured at rest and in response to a 3-minute arithmetic stress task.
      Participants were classified as current, ex-, or non-smokers by their response to
      a simple prompt. Smokers had significantly smaller SBP and DBP reactions to acute
      stress than ex- and non-smokers; current and ex-smokers had lower HR reactivity.
      These effects remained significant following adjustment for a host of variables
      likely to be associated with reactivity and/or smoking. Although the act of
      smoking acutely increases haemodynamic activity, the present findings contribute
      to a growing body of literature showing that smokers have blunted reactivity to
      mental stress. They also support the hypothesis that blunted reactivity may be
      characteristic of a range of dependencies. The present results also suggest that
      smoking status needs to be considered in the design and analysis of stress
      reactivity studies.

PMID- 19397940
TI  - Productivity of cyclohexanone oxidation of the recombinant Corynebacterium
      glutamicum expressing chnB of Acinetobacter calcoaceticus.
AB  - The biocatalytic efficiency of recombinant Corynebacterium glutamicum expressing
      the chnB gene encoding cyclohexanone monooxygenase (CHMO) of Acinetobacter
      calcoaceticus NCIMB 9871 was investigated. Optimization of an expression system
      and induction conditions enabled the recombinant biocatalyst to produce CHMO to a
      specific activity of ca. 0.5 U mg(-1) protein. Tight control of feeding of an
      energy source (i.e., glucose) and dissolved oxygen tension during fed-batch
      culture-based biotransformation allowed the cells to produce epsilon-caprolactone
      to a concentration of 16.0 g l(-1). The specific and volumetric productivity for
      cyclohexanone oxidation were 0.12 g g drycells(-1)h(-1) (17.5 U g(-1) of dry
      cells) and 2.3 g l(-1)h(-1) (330 U l(-1)), respectively. These values correspond
      to over 5.4- and 2.7-fold of recombinant Escherichia coli expressing the same
      gene under similar reaction conditions. It could be concluded that the
      recombinant C. glutamicum is a promising biocatalyst for Baeyer-Villiger
      oxidations.

PMID- 19397941
TI  - Effects of obestatin on feeding and body weight after standard or cafeteria diet
      in the rat.
AB  - Obestatin is a gastric derived 23 amino acid peptide, which has shown anorectic
      effects in a number of experimental paradigms after both peripheral and central
      administration. On the other hand, several researchers were not able to confirm
      these data. Since all previous experiments have been performed in animals fed a
      standard laboratory diet, we studied obestatin effects in male Wistar rats fed
      both a standard laboratory chow (STD) diet (3.5% fat, 63% carbohydrate, 14%
      protein, 19.5% other components without caloric value; 3.20 kcal/g) and a highly
      palatable cafeteria-style (CAF) diet (30% fat, 56% carbohydrate, 14% protein;
      4.20 kcal/g). Vehicle or obestatin (10, 50 or 100 nmol/kg) was injected
      intraperitoneally daily for 12 days. In STD diet rats, obestatin decreased daily
      caloric intake and body weight gain compared to vehicle treated rats. The
      anorectic and weight reducing effects of obestatin treatment were evidenced since
      day 6 and day 8 of treatment, respectively, and were consistent through the end
      of treatment. On the other hand, in CAF diet rats, obestatin treatment did not
      modify either daily caloric intake or body weight gain. In CAF diet rats, the
      percentage intake from standard food was decreased, balanced by an increase in
      cafeteria food intake. Obestatin treatment affected neither water consumption nor
      the intake of any specific food within the cafeteria diet. In conclusion,
      obestatin decreases caloric intake and body weight gain, but only in rats fed a
      STD diet.

PMID- 19397942
TI  - Hybrid peptides attenuate cytotoxicity of beta-amyloid by inhibiting its
      oligomerization: implication from solvent effects.
AB  - Abnormal assembly of monomeric beta-amyloid (Abeta) in Alzheimer's disease leads
      to the formation of most neurotoxic oligomers in vivo. In this study, we explored
      a linking strategy to design hybrid peptides, by combining the Abeta recognition
      motif and the solvent disruptive sequences. We found that in vitro all synthetic
      peptides with the recognition motif can affect Abeta fibrillization and alter the
      morphology of Abeta aggregates variously, different from those without the
      recognition motif. The effects of peptides containing recognition motif on Abeta
      aggregation correlate with their abilities to change the surface tension of
      solutions. In addition, compounds with the recognition motif, not those without
      such motif, can inhibit cytotoxicity of Abeta in cell culture probably by
      decreasing the amount of toxic Abeta oligomers. These results indicate that
      recognition domain and solvent effect should be considered as important factors
      when designing molecules to target Abeta aggregation.

PMID- 19397943
TI  - Molecular cloning and expression of two melanin-concentrating hormone receptors
      in goldfish.
AB  - Melanin-concentrating hormone (MCH) is a neurohypophysial hormone and induces
      melanin aggregation in the skin in teleosts. MCH also has multiple roles in the
      central regulation of food intake in teleosts and mammals. MCH receptors (MCH-R)
      are among type I G-protein-coupled receptors. Here, we cloned two MCH receptors
      from goldfish, Carassius auratus. The amino acid sequence of goldfish MCH-R1 had
      57-88% homology with fish MCH-R1 and 49-50% homology with mammalian MCH-R1, while
      the amino acid sequence of goldfish MCH-R2 had 72-92% homology with fish MCH-R2
      and 32% homology with human MCH-R2. Phylogenetic analysis showed that these two
      MCH-Rs are orthologous to the respective mammalian MCH-Rs. The common amino acid
      residues for ligand binding, signal transduction, and receptor conformation were
      well conserved in these receptors, although some intracellular basic-amino-acid
      rich domains, which have been shown to exist in human MCH-R1 and MCH-R2, were
      absent in goldfish MCH-R2. When stably expressed in HEK293 cells, both goldfish
      MCH-R1 and MCH-R2 displayed a strong, dose-dependent, transient elevation of
      intracellular calcium in response to salmon MCH (EC(50)=0.8nM and 31.8nM,
      respectively). In contrast to goldfish MCH-R2, goldfish MCH-R1 signaling is not
      sensitive to pertussis toxin, suggesting an exclusive Galphaq coupling of
      goldfish MCH-R1 in the mammalian cell-based assay. Reverse transcriptase PCR
      revealed that both MCH-R1 and MCH-R2 mRNA are distributed in various tissues in
      goldfish. The various tissues including the brain and skin express both MCH-R1
      and MCH-R2. These results suggest that these functional receptors mediate
      multiple effects of MCH in goldfish.

PMID- 19397944
TI  - MCH receptor peptide agonists and antagonists.
AB  - Melanin-concentrating hormone (MCH) is an important neuropeptide hormone involved
      in multiple physiological processes. Peptide derivatives of MCH have been
      developed as tools to aid research including potent radioligands, receptor
      selective agonists, and potent antagonists. These tools have been used to further
      understand the role of MCH in physiology, primarily in rodents. However, the
      tools could also help elucidate the role for MCHR1 and MCHR2 in mediating MCH
      signaling in higher species.

PMID- 19397946
TI  - NOD2/CARD15 polymorphisms impair innate immunity and increase susceptibility to
      gastric cancer in an Italian population.
AB  - In the present case-control study we investigated the potential role of CARD15
      R702W, G908R, and 1007fs polymorphisms in Italian gastric cancer patients. The
      study population consisted of 170 gastric cancer patients and 156 controls.
      Unconditional regression (odds ratios and 95% confidence interval) was used to
      investigate the association of the studied polymorphisms with gastric cancer.
      Higher allele frequencies of R702W and 1007fs polymorphisms were observed in
      patients with gastric cancer compared with controls (8.53 vs 2.3 and 9.4 vs 0.7,
      respectively). CARD15 R702W and 1007fs polymorphisms were significantly
      correlated with gastric cancer incidence (p < 0.0001, p < 0.0001, respectively).
      No correlation was found upon analyzing the G908R single nucleotide polymorphism
      (SNP). Our study reports an increased susceptibility to gastric cancer in Italian
      populations when R702W and 1007fs polymorphisms in the coding region of CARD15
      are present. The interaction between NOD-induced proinflammatory cytokines on
      gastric mucosa and environmental carcinogens could represent one of the
      mechanisms by which CARD15 polymorphisms increase the susceptibility to gastric
      cancer. Meta-analyses of these SNPs and further analyses of additional
      polymorphisms/haplotypes in NOD genes will help determine their role in
      carcinogenesis.

PMID- 19397945
TI  - Brain regional distribution of GABA(A) receptors exhibiting atypical GABA
      agonism: roles of receptor subunits.
AB  - The major inhibitory neurotransmitter in the brain, gamma-aminobutyric acid
      (GABA), has only partial efficacy at certain subtypes of GABA(A) receptors. To
      characterize these minor receptor populations in rat and mouse brains, we used
      autoradiographic imaging of t-butylbicyclophosphoro[(35)S]thionate ([(35)S]TBPS)
      binding to GABA(A) receptors in brain sections and compared the displacing
      capacities of 10mM GABA and 1mM 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol
      (THIP), a competitive GABA-site agonist. Brains from GABA(A) receptor alpha1,
      alpha4, delta, and alpha4+delta subunit knockout (KO) mouse lines were used to
      understand the contribution of these particular receptor subunits to "GABA
      insensitive" (GIS) [(35)S]TBPS binding. THIP displaced more [(35)S]TBPS binding
      than GABA in several brain regions, indicating that THIP also inhibited GIS
      binding. In these regions, GABA prevented the effect of THIP on GIS-binding. GIS
      binding was increased in the cerebellar granule cell layer of delta KO and
      alpha4+delta KO mice, being only slightly diminished in that of alpha1 KO mice.
      In the thalamus and some other forebrain regions of wild-type mice, a significant
      amount of GIS-binding was detected. This GIS-binding was higher in alpha4 KO
      mice. However, it was fully abolished in alpha1 KO mice, indicating that the
      alpha1 subunit was obligatory for the GIS-binding in the forebrain. Our results
      suggest that native GABA(A) receptors in brain sections showing reduced
      displacing capacity of [(35)S]TBPS binding by GABA (partial agonism) minimally
      require the assembly of alpha1 and beta subunits in the forebrain and of alpha6
      and beta subunits in the cerebellar granule cell layer. These receptors may
      function as extrasynaptic GABA(A) receptors.

PMID- 19397947
TI  - Effects of co-administration of dietary sodium arsenite and an NADPH oxidase
      inhibitor on the rat bladder epithelium.
AB  - Arsenite (As(III)), an inorganic arsenical, is a known human carcinogen, inducing
      tumors of the skin, urinary bladder and lung. It is metabolized to organic
      methylated arsenicals. Oxidative stress has been suggested as a mechanism for
      arsenic-induced carcinogenesis. Reactive oxygen species (ROS) can be important
      factors for carcinogenesis and tumor progression. Nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase is known to produce intracellular ROS,
      therefore, we investigated the ability of apocynin (acetovanillone), an NADPH
      oxidase inhibitor, to inhibit the cytotoxicity and regenerative cell
      proliferation of arsenic in vitro and in vivo. Apocynin had similar effects in
      reducing the cytotoxicity of As(III) and dimethylarsinous acid (DMA(III)) in rat
      urothelial cells in vitro. When tested at the same concentrations as apocynin,
      other antioxidants, such as l-ascorbate and N-acetylcysteine, did not inhibit
      As(III)-induced cytotoxicity but they were more effective at inhibiting DMA(III)
      induced cytotoxicity compared with apocynin. In vivo, female rats were treated
      for 3 weeks with 100ppm As(III). Immunohistochemical staining for 8-hydroxy-2'
      deoxyguanosine (8-OHdG) showed that apocynin reduced oxidative stress partially
      induced by As(III) treatment on rat urothelium, and significantly reduced the
      cytotoxicity of superficial cells detected by scanning electron microscopy (SEM).
      However, based on the incidence of simple hyperplasia and the bromodeoxyuridine
      (BrdU) labeling index, apocynin did not inhibit As(III)-induced urothelial cell
      proliferation. These data suggest that the NADPH oxidase inhibitor, apocynin, may
      have the ability to partially inhibit arsenic-induced oxidative stress and
      cytotoxicity of the rat bladder epithelium in vitro and in vivo. However,
      apocynin did not inhibit the regenerative cell proliferation induced by arsenite
      in a short-term study.

PMID- 19397948
TI  - Comparative chlorpyrifos pharmacokinetics via multiple routes of exposure and
      vehicles of administration in the adult rat.
AB  - Chlorpyrifos (CPF) is a commonly used organophosphorus pesticide. A number of
      toxicity and mechanistic studies have been conducted in animals, where CPF has
      been administered via a variety of different exposure routes and dosing vehicles.
      This study compared chlorpyrifos (CPF) pharmacokinetics using oral, intravenous
      (IV), and subcutaneous (SC) exposure routes and corn oil, saline/Tween 20, and
      dimethyl sulfoxide (DMSO) as dosing vehicles. Two groups of rats were co
      administered target doses (5 mg/kg) of CPF and isotopically labeled CPF (L-CPF).
      One group was exposed by both oral (CPF) and IV (L-CPF) routes using saline/Tween
      20 vehicle; whereas, the second group was exposed by the SC route using two
      vehicles, corn oil (CPF) and DMSO (L-CPF). A third group was only administered
      CPF by the oral route in corn oil. For all treatments, blood and urine time
      course samples were collected and analyzed for 3,5,6-trichloro-2-pyridinol
      (TCPy), and isotopically labeled 3,5,6-trichloro-2-pyridinol (L-TCPy). Peak
      TCPy/L-TCPy concentrations in blood (20.2 micromol/l), TCPy/L-TCPy blood AUC
      (94.9 micromol/lh), and percent of dose excreted in urine (100%) were all highest
      in rats dosed orally with CPF in saline/Tween 20 and second highest in rats dosed
      orally with CPF in corn oil. Peak TCPy concentrations in blood were more rapidly
      obtained after oral administration of CPF in saline/Tween 20 compared to all
      other dosing scenarios (>1.5 h). These results indicate that orally administered
      CPF is more extensively metabolized than systemic exposures of CPF (SC and IV),
      and vehicle of administration also has an effect on absorption rates. Thus,
      equivalent doses via different routes and/or vehicles of administration could
      potentially lead to different body burdens of CPF, different rates of
      bioactivation to CPF-oxon, and different toxic responses. Simulations using a
      physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF
      are consistent with these possibilities. These results suggest that exposure
      route and dosing vehicle can substantially impact target tissue dosimetry. This
      is of particular importance when comparing studies that use varying exposure
      paradigms, which are then used for extrapolation of risk to humans.

PMID- 19397949
TI  - Habituation and sensitization of protective reflexes: dissociation between
      cardiac defense and eye-blink startle.
AB  - We examined the habituation and recovery of two protective reflexes, cardiac
      defense and eye-blink startle, simultaneously elicited by a white noise of 500ms
      as a function of the time interval between stimulus presentations. Participants
      were 90 volunteers (54 women) randomly distributed into 6 inter-trial interval
      (ITI) conditions. They all received three presentations of the stimulus with a
      time interval of 30min between the first and third noise. The timing of the
      second noise was manipulated in six steps, using a between-group design, in order
      to increase the ITI between Trials 1 and 2 and symmetrically decrease the ITI
      between Trials 2 and 3. Cardiac defense showed fast habituation at the shortest
      ITI (2.5min), but reduced habituation and increased recovery at the longest ITI
      (27.5min). In contrast, eye-blink startle showed sensitization irrespective of
      the ITI. This pattern of findings highlights dissociations between protective
      reflexes when simultaneously examined. The results are discussed in the context
      of the cascade model of defense reactions.

PMID- 19397950
TI  - Energy efficiency of information transmission by electrically coupled neurons.
AB  - The generation of spikes by neurons is energetically a costly process. This paper
      studies the consumption of energy and the information entropy in the signalling
      activity of a model neuron both when it is supposed isolated and when it is
      coupled to another neuron by an electrical synapse. The neuron has been modelled
      by a four-dimensional Hindmarsh-Rose type kinetic model for which an energy
      function has been deduced. For the isolated neuron values of energy consumption
      and information entropy at different signalling regimes have been computed. For
      two neurons coupled by a gap junction we have analyzed the roles of the membrane
      and synapse in the contribution of the energy that is required for their
      organized signalling. Computational results are provided for cases of identical
      and nonidentical neurons coupled by unidirectional and bidirectional gap
      junctions. One relevant result is that there are values of the coupling strength
      at which the organized signalling of two neurons induced by the gap junction
      takes place at relatively low values of energy consumption and the ratio of
      mutual information to energy consumption is relatively high. Therefore,
      communicating at these coupling values could be energetically the most efficient
      option.

PMID- 19397951
TI  - Association of KIBRA and memory.
AB  - We report on the association of KIBRA with memory in two samples of older
      individuals assessed on either memory for semantically unrelated word stimuli
      (Rey Auditory Verbal Learning Test, n=2091), or a measure of semantically related
      material (the WAIS Logical Memory Test of prose-passage recall, n=542). SNP
      rs17070145 was associated with delayed recall of semantically unrelated items,
      but not with immediate recall for these stimuli, nor with either immediate or
      delayed recall for semantically related material. The pattern of results suggests
      a role for the T-->C substitution in intron 9 of KIBRA in a component of episodic
      memory involved in long-term storage but independent of processes shared with
      immediate recall such as rehearsal involved in acquisition and rehearsal or
      processes.

PMID- 19397952
TI  - Response to the increase of oxidative stress and mutation of mitochondrial DNA in
      aging.
AB  - In the aging process, mitochondrial function gradually declines with an increase
      of mutations in mitochondrial DNA (mtDNA) in tissue cells. Some of the aging
      associated mtDNA mutations have been shown to result in not only inefficient
      generation of ATP but also increased production of reactive oxygen species (ROS)
      such as superoxide anions (O2-) and hydrogen peroxide (H2O2) in the mitochondria
      of aging tissues. Extensive studies have revealed that such an increase of
      oxidative stress is a contributory factor for alterations in the expression and
      activities of antioxidant enzymes and increased oxidative damage to DNA, RNA,
      proteins, and lipids in tissues and cultured cells from elderly subjects.
      Recently, we observed that gene expression of several proteins and enzymes
      related to iron metabolism is altered and that aconitase is extremely susceptible
      to oxidative damage in senescent skin fibroblasts and in cybrids harboring aging
      associated A8344G mutation of mtDNA. Of great importance is the perturbation at
      the protein and activity levels of several enzymes containing iron-sulfur
      clusters in skin fibroblasts of elderly subjects. Taken together, these findings
      suggest that cellular response to oxidative stress and oxidative damage elicited
      by mitochondrial dysfunction and/or mtDNA mutations plays an important role in
      human aging.

PMID- 19397953
TI  - Morphine induces DNA damage and P53 activation in CD3+ T cells.
AB  - BACKGROUND: Morphine has been shown to affect the function of immune system, but
      the precise mechanism remains to be elucidated. The present study was aimed to
      clarify the mechanism for the morphine-induced immune suppression by analyzing
      the direct effect of morphine on human CD3+ T cells. METHODS: To identify genes
      up-regulated by action of morphine on the opioid receptor expressed in CD3+ T
      cells, PCR-select cDNA subtraction was performed by the use of total RNA from
      human CD3+ T cells treated with morphine in the presence and absence of naloxone.
      RESULTS: We show that p53 and damage-specific DNA binding protein 2 (ddb2) genes
      are up-regulated by morphine in a naloxone-sensitive manner. Furthermore, the
      results indicate that DNA damage, quantified by apurinic-apyrimidinic site
      counting assay and phosphorylation of Ser-15 in P53 protein, is induced in CD3+ T
      cells by morphine in a naloxone-sensitive manner. GENERAL SIGNIFICANCE: Because
      it was shown that only the kappa opioid receptor gene is expressed in CD3+ T
      cells in the opioid receptor family, the present study suggests that morphine
      induces DNA damage through the action on the kappa opioid receptor, which leads
      to immune suppression by activation of P53-mediated signal transduction.

PMID- 19397954
TI  - Anti-cariogenic effects of polyphenols from plant stimulant beverages (cocoa,
      coffee, tea).
AB  - Polyphenols occurring in cocoa, coffee and tea can have a role in the prevention
      of cariogenic processes, due to their antibacterial action. Cocoa polyphenol
      pentamers significantly reduce biofilm formation and acid production by
      Streptococcus mutans and S. sanguinis. In the same way, trigonelline, caffeine
      and chlorogenic acid occurring in green and roasted coffee interfere with S.
      mutans adsorption to saliva-coated hydroxyapatite beads. Studies carried out on
      green, oolong and black tea indicate that tea polyphenols exert an anti-caries
      effect via an anti-microbial mode-of-action, and galloyl esters of (-)
      epicatechin, (-)-epigallocatechin and (-)-gallocatechin show increasing
      antibacterial activities. The anti-cariogenic effects against alpha-haemolytic
      streptococci showed by polyphenols from cocoa, coffee, and tea suggest further
      studies to a possible application of these beverages in the prevention of
      pathogenesis of dental caries.

PMID- 19397955
TI  - DNA methylation analysis of the mammalian PEG3 imprinted domain.
AB  - In this study, we performed the first systematic survey of DNA methylation status
      of the CpG islands of the PEG3 (Paternally expressed gene 3) imprinted domain in
      the mouse, cow, and human genomes. Previous studies have shown that the region
      surrounding the first exon of PEG3 contains a differentially methylated CpG
      island. In addition, we have discovered two previously unreported differentially
      methylated regions (DMR): one in the promoter region of mouse Zim3 and another in
      the promoter region of human USP29. In the cow, the Peg3-CpG island was the only
      area that showed DMR status. We have also examined the methylation status of
      several CpG islands in this region using human tumor-derived DNA. The CpG islands
      near PEG3 and USP29 both showed hypermethylation in DNA derived from breast and
      ovarian tumors. Overall, this study shows that the PEG3 imprinted domain of
      humans, cows, and mice contains differing numbers of DMRs, but the PEG3-CpG
      island is the only DMR that is conserved among these three species.

PMID- 19397957
TI  - The complete mitochondrial genome of Cephalothrix simula (Iwata) (Nemertea:
      Palaeonemertea).
AB  - The first complete mitochondrial genome sequence for a nemertean, Cephalothrix
      simula, was determined by conventional and long PCR and sequencing with primer
      walking methods. This circular genome is 16,296 bp in size and encodes 37 genes
      (13 protein-coding genes, 2 ribosomal RNAs, and 22 transfer RNAs) typically found
      in metazoans. All genes are encoded on H-strand except two tRNAs (trnT and trnP).
      It differs from those reported for other metazoans, but some gene junctions are
      shared with those of other protostomes. Structure of the mitochondrial genome of
      C. simula is mostly concordant with the partial mitochondrial genome known for
      Cephalothrix rufifrons, but notable differences include three large indel events
      and transposition of 2 tRNAs. Nucleotide composition of the mitochondrial genome
      of C. simula is highly A+T biased. The compositional skew is strongly reflected
      in the codon-usage patterns and the amino acid compositions of the mitochondrial
      proteins. An AT-rich noncoding region with potential to form stem-loop structures
      may be involved in the initiation of replication or transcription. Gene
      adjacencies and phylogenetic analysis based on the 12 concatenated amino acid
      sequences (except atp8) of mitochondrial protein-coding genes show that the
      nemertean is close to the coelomate lophotrochozoans, rather than the acoelomate
      platyhelminths.

PMID- 19397956
TI  - Genetic differentiation among local populations of medaka fish (Oryzias latipes)
      evaluated through grid- and deme-based sampling.
AB  - The medaka (Oryzias latipes), a tiny fish, has been an excellent experimental
      model for molecular and developmental genetics, and is expected for being a
      "vertebrate" model animal for population genetics, because 1) there is abundant
      within-species variation, and 2) the whole genome sequence has been determined
      for one of the inbred strains. In spite of its potential usefulness, there is no
      comprehensive study on quantifying between- and within-population genetic
      diversity of wild medaka. To investigate population structure, we examine
      nucleotide sequences of the non-coding D-loop region and the cytochrome b gene of
      the mitochondrial (mt) genome for medaka individuals collected with distinct two
      sampling-methods. Using deme-based sampling, out of 373 total individuals from
      three local (two wild and one biotope) populations only 16 distinct sequence
      types of mt D-loop are found. However, we find 26 D-loop types in 35 individuals
      collected with grid-based sampling from various geographical regions in East
      Asia. We carry out statistical tests to evaluate the distribution pattern of
      nucleotide frequencies among segregating sites under the standard neutral model,
      and we show that the deme-sampled populations might have experienced population
      size reduction and/or sub-structuring caused by natural or artificial migration.
      The reduction of genetic variation has been driven more markedly in the
      populations from the biotope, suggesting that human activities can pose an impact
      on the demographic history of medaka. Nevertheless, our results suggest that the
      grid-based sampling gives more abundant variations than the deme-based sampling,
      while the deme-based sampling gives more information about the local-wild
      characteristics of allele frequency spectrum than grid-based sampling. This could
      be a basis of strategy to use medaka as a vertebrate model animal for comparative
      population genomics.

PMID- 19397958
TI  - The complete mitochondrial genome of the large-headed frog, Limnonectes
      bannaensis (Amphibia: Anura), and a novel gene organization in the vertebrate
      mtDNA.
AB  - We determined the complete nucleotide sequence of the mitochondrial (mt) genome
      of the large-headed frog, Limnonectes bannaensis (Amphibia, Anura) by using
      polymerase chain reaction (PCR). The entire mtDNA sequence is 16,867 bp in length
      with a novel case of tRNAs in vertebrates. This mt genome is characterized by
      three distinctive features: (1) a tandem duplication of tRNA(Met) gene is
      observed, (2) the tRNA(Ala), tRNA(Asn), tRNA(Cys) and tRNA(Glu) genes coded on
      the L-strand are absent from the L. bannaensis mtDNA, the tRNA(Cys) and tRNA(Glu)
      genes change into tRNA pseudogenes by reason of degenerative anticodon, and a
      noncoding sequence of 206 nt long (NC1) has replaced the original position of
      other two tRNAs, (3) besides NC1, another three noncoding spacers (NC2-4) longer
      than 50 bp are found in the broken WANCY region and the region NC3-ND5-NC4-ND6
      PsiE-Cytb-CR of the new sequence. These features could be explained by a model of
      gene duplication and deletion. The new sequence data was used to assess the
      phylogenetic relationships among 25 species of Anura using neighbor-joining,
      Bayesian, and maximum likelihood methods, and the phylogenetic tree shows the
      rice frog Fejervarya limnocharis is closest to L. bannaensis in the study.

PMID- 19397959
TI  - Global transcription profiling and virulence potential of Streptococcus
      pneumoniae after serial passage.
AB  - Streptococcus pneumoniae, a facultative human pathogen associated with wide
      variety of diseases, such as pneumonia, meningitis, sepsis and otitis media.
      Factors involved in the initial colonization, survival and etiology of this
      commensal bacteria in the human host from the ex vivo environment is still not
      clearly understood. Here, we report alterations in global transcriptional
      profiles of S. pneumoniae 6304 serotype 4 after 50 passages (50P) and 100
      passages (100P) on laboratory media to better understand gene expression
      strategies employed by the bacterium during progression from the nasopharynx to
      the blood. The results show that six-fold more genes were differentially
      expressed after 100P as compared to 50P. After 100P on blood agar plates, 726
      genes (33%) of 2192 genes in the S. pneumoniae genome were differentially
      expressed. Moreover, the majority of these genes (68%) were expressed at higher
      levels with increasing passage number and from different functional groups.
      Significantly, all the genes present in Region of Diversity 10 (RD10) are
      required for virulence during blood stream infection showed enhanced expression
      after passage. However, there was no significant decrease in the LD(50) of serial
      passage strains compare to single passage strain in a mouse challenge model.
      Overall, our data suggest that bacteria adapt to extended laboratory passage by
      substantially altering gene expression. Furthermore, extended passage on blood
      agar plates reduces the expression of genes associated with initial colonization
      and adherence but enhances the expression of genes needed for systemic infection.

PMID- 19397960
TI  - DRDE-07 and its analogues as promising cytoprotectants to nitrogen mustard (HN-2)
      -an alkylating anticancer and chemical warfare agent.
AB  - Nitrogen mustard (HN-2), also known as mechlorethamine, is an alkylating
      anticancer agent as well as blister inducing chemical warfare agent. We evaluated
      the cytoprotective efficacy of amifostine, DRDE-07 and their analogues, and other
      antidotes of mustard agents against HN-2. Administration of 1 LD(50) of HN-2
      (20mg/kg) percutaneously, decreased WBC count from 24h onwards. Liver glutathione
      (GSH) level decreased prominently and the maximum depletion was observed on 7th
      day post-HN-2 administration. Oxidised glutathione (GSSG) level increased
      significantly at 24h post-administration and subsequently showed a progressive
      decrease. Hepatic malondialdehyde (MDA) level and percent DNA damage increased
      progressively following HN-2 administration. The spleen weight decreased
      progressively and reached a minimum on 3-4 days with subsequent increase. The
      antidotes were administered repeatedly for 4 and 8 days after percutaneous
      administration of single sublethal dose (0.5 and 0.25 LD(50)) of HN-2. Treatment
      with DRDE-07, DRDE-30 and DRDE-35 significantly protected the changes in spleen
      weight, WBC count, GSH, GSSG, MDA and DNA damage following HN-2 administration
      (0.5 and 0.25 LD(50)). There was no alteration in the transaminases (AST and
      ALT), and alkaline phosphatase (ALP) activities, neither with HN-2 nor with
      antidotes. The present study shows that HN-2 is highly toxic by percutaneous
      route and DRDE-07, DRDE-30 and DRDE-35 can partially protect it.

PMID- 19397961
TI  - Sulphur mustard induces time- and concentration-dependent regulation of NO
      synthesizing enzymes.
AB  - Sulphur mustard (SM) is a chemical warfare agent that causes erythema and
      blistering of the skin with a latency of several hours. Although SM is known for
      almost 200 years the cellular mechanisms involved in the damaging process are not
      fully understood. There is evidence that changes in nitric oxide (*NO), reactive
      oxygen species (ROS) and reactive nitrogen species (RNS) might be involved in the
      damaging process. AIM: To find out more about the pathophysiology of SM, we
      investigated the initial formation of biochemical markers of nitrosative and
      oxidative stress as well as activation (translocation from plasma-membrane) and
      upregulation of eNOS and iNOS, respectively. METHODS: Human immortalized
      keratinocytes (HaCaT cell line) were exposed to SM (100 microM or 300 microM) for
      30 min. Cells were fixed after 1h, 3h or 6h of incubation in SM-free medium and
      immunostained. Live cell experiments were performed using the NO-sensitive dye
      DAF2-DA. In order to assess cell viability after BH(4) supplementation, we
      analyzed apoptosis using CDD-ELISA. RESULTS: SM significantly increased
      biochemical markers of nitrosative and oxidative stress already 1h after
      exposure. Moreover, the NO producing enzymes eNOS and iNOS showed concentration-
      and time-dependent changes in their activation or expression levels. Initially,
      live cell imaging experiments could not confirm NO production after SM exposure.
      Only when cells were supplemented with tetrahydrobiopterine, stable NO production
      was detectable. Apoptotic activity was increased due to SM exposure and could be
      reduced after BH(4) treatment. CONCLUSION: Our data point towards concentration-
      and time-dependent formation of iNOS and activation of eNOS due to translocation
      from plasma-membrane. Live cell experiments yielded first indications of
      catalytic decoupling of NOS that could be reversed by supplementation with
      tetrahydrobiopterin (BH(4)). Addition of BH(4) 1h after SM exposure significantly
      decreased apoptosis compared to the unsupplemented control.

PMID- 19397962
TI  - Chronic exposure to perfluorododecanoic acid disrupts testicular steroidogenesis
      and the expression of related genes in male rats.
AB  - Perfluorododecanoic acid (PFDoA), a synthetic perfluorinated chemical, has been
      detected in environmental matrices, wildlife, and human serum. Its potential
      health risk for humans and animals has raised public concern. However, the
      effects of chronic PFDoA exposure on male reproduction remain unknown. The aim of
      this study was to determine the effects of chronic PFDoA exposure (110 days) on
      testosterone biosynthesis and the expression of genes related to steroidogenesis
      in male rats. In this study, we examined the serum levels of sex hormones, growth
      hormone, and insulin in male rats. Testicular morphology and the expression of
      key genes and proteins in testosterone biosynthesis were also analyzed. Markedly
      decreased serum testosterone levels were recorded after 110 days of PFDoA
      exposure at 0.2mg PFDoA/kg/day and 0.5mg PFDoA/kg/day, and cast-off cells were
      observed in some seminiferous tubules in testes exposed to 0.5mg PFDoA/kg/day.
      PFDoA exposure resulted in significantly decreased protein levels of
      steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage
      enzyme (P450scc), along with significantly reduced mRNA levels of insulin-like
      growth factor I (IGF-I), insulin-like growth factor I receptor (IGF-IR), and
      interleukin 1alpha (IL-1alpha) in rat testes at 0.2mg/kg/day and 0.5mg/kg/day. In
      addition, PFDoA exposure also affected the expression of some genes in the
      hypothalamo-neurohypophyseal system. However, PFDoA did not affect the expression
      of 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase, or aromatase in testis
      and liver. These findings demonstrate that chronic PFDoA exposure disrupts
      testicular steroidogenesis and expression of related genes in male rats. Multiple
      factors may be involved in the inhibition of testosterone by PFDoA.

PMID- 19397963
TI  - A simple and fast method for the determination of selected organohalogenated
      compounds in serum samples from the general population.
AB  - Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) have been
      widely used in industry and agriculture. Due to their persistence and
      bioaccumulation, they were globally spread in the environment and may still be
      found in environmental and biological media, despite the international
      restrictions on production and use. The main aim of our study was to develop a
      simple and fast method suitable for the establishment of the reference values for
      15 PCB congeners and 16 OCPs in general population subgroups. A cost- and time
      saving screening procedure using gas chromatography coupled with low-resolution
      mass spectrometry, was improved and validated before application to the analysis
      of real samples. The overall method was validated including uncertainty
      measurement. Preliminary field data were collected from 95 volunteers living in
      two Italian areas. HCB, p,p'-DDE, PCB 153, PCB 138 and PCB 180 were the most
      frequently detected compounds. Age and residence area were found to be
      significant variables for the most abundant compounds, while no correlation
      between serum concentrations and gender was observed. Our results suggest that
      long-banned substances, including PCBs and the pesticides HCB and DDT's breakdown
      product, are still detectable in the general population.

PMID- 19397964
TI  - The impact of size on tissue distribution and elimination by single intravenous
      injection of silica nanoparticles.
AB  - Many approaches for the application of nano-sized particles to the human body as
      nanotechnology have been recently developed. The size of nanoparticles is related
      to their useful character and also plays a key role in toxicity. Since this
      surface area can interact with biological components of cells, nanoparticles can
      be more reactive in than larger particles. In the present study, a fluorescence
      dye-labeled 50, 100 and 200 nm-sized silica particle suspension was intravenously
      injected into mice to identify the toxicity, tissue distribution and excretion of
      silica nanoparticles in vivo. Incidence and severity of inflammatory response was
      transiently increased with injection of 200 and 100 nm silica nanoparticles
      within 12h. But there was no significant response related to injection of 50 nm
      particles. The silica particles of 50, 100 and 200 nm were cleared via urine and
      bile. The 50 nm silica nanoparticles cleared to urine and bile than 100 nm and
      particles of 200 nm existed at lower concentration than other two smaller
      particles in urine and feces. Silica nanoparticles were trapped by macrophages in
      the spleen and liver and remained there until 4 weeks after the single injection.

PMID- 19397965
TI  - Hepatocyte growth factor, vascular endothelial growth factor, glial cell-derived
      neurotrophic factor and nerve growth factor are differentially affected by early
      chronic ethanol or red wine intake.
AB  - Ethanol intake during pregnancy and lactation induces severe changes in brain and
      liver throughout mechanisms involving growth factors. These are signaling
      molecules regulating survival, differentiation, maintenance and connectivity of
      brain and liver cells. Ethanol is an element of red wine which contains also
      compounds with antioxidant properties. Aim of the study was to investigate
      differences in hepatocyte growth factor (HGF), vascular endothelial growth factor
      (VEGF), glial cell-derived neurotrophic factor (GDNF) and nerve growth factor
      (NGF) in brain areas and liver by ELISA of 1-month-old male mice exposed
      perinatally to ethanol at 11 vol.% or to red wine at same ethanol concentration.
      Ethanol was administered before and during pregnancy up to pups' weaning. Ethanol
      per se elevated HGF in liver and cortex, potentiated liver VEGF, reduced GDNF in
      the liver and decreased NGF content in hippocampus and cortex in the offspring.
      We did not find changes in HGF or NGF due to red wine exposure. However, we
      revealed elevation in VEGF levels in liver and reduced GDNF in the cortex of
      animals exposed to red wine but the VEGF liver increase was more marked in
      animals exposed to ethanol only compared to the red wine group. In conclusion the
      present findings in the mouse show differences in ethanol-induced toxicity when
      ethanol is administered alone or in red wine that may be related to compounds
      with antioxidant properties present in the red wine.

PMID- 19397966
TI  - Induction of PUMA-alpha and down-regulation of PUMA-beta expression is associated
      with benzo(a)pyrene-induced apoptosis in MCF-7 cells.
AB  - Benzo(a)pyrene (BP) forms benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA
      adducts in human breast adenocarcinoma MCF-7 cells, leading to p53 protein
      induction and phosphorylation. Although BP-induced apoptosis in rodent cells is
      known, it is still unclear in human cells. Here we have analyzed the effects of
      BP on p53 related apoptotic proteins, cell cycle and cell death in MCF-7 cells.
      PUMA-protein (p53 up-regulated modulator of apoptosis) levels were changed after
      BP exposure so that PUMA-alpha protein was statistically significantly increased
      whereas PUMA-beta protein was statistically significantly decreased. PUMA-protein
      levels were also investigated in ZR-75-1 cells, where PUMA-alpha protein was
      statistically significantly increased. Cytochrome c, which is released from
      mitochondria during apoptosis to form the apoptosome, was increased in
      cytoplasmic fraction after BP exposure in MCF-7 cells. Increased apoptosis was
      also seen after 48 and 72 h BP exposure (2.5 and 5 microM). In addition, BP
      decreased dose dependently cell viability (2.5 and 5 microM) and increased ROS
      formation (1 and 10 microM). Our results suggest that PUMA-alpha protein is
      involved in BP-induced cell death most likely through a p53 dependent apoptotic
      pathway.

PMID- 19397967
TI  - Presence of aromatase and estrogen receptor alpha in the inner ear of zebra
      finches.
AB  - Sex differences in song behavior and in the neural system controlling song in
      songbirds are well documented but relatively little is known about sex
      differences in hearing. We recently demonstrated the existence of sex differences
      in auditory brainstem responses in a songbird species, the zebra finch
      (Taeniopygia guttata). Many sex differences are regulated by sex steroid hormone
      action either during ontogeny or in adulthood. As a first step to test the
      possible implication of sex steroids in the control of sex differences in the
      zebra finch auditory system, we evaluated via immunocytochemistry whether
      estrogens are produced and act in the zebra finch inner ear. Specifically we
      examined the distribution of aromatase, the enzyme converting testosterone into
      an estrogen, and of estrogen receptors of the alpha subtype (ERalpha) in adult
      zebra finch inner ears. The anatomy of the basilar papillae was visualized by
      fluorescein-phalloidin, which delineated the actin structure of hair cells and
      supporting cells at their apical surface. Whole mount preparations of basilar
      papillae stained by immunocytochemistry revealed in both males and females an
      abundant aromatase distribution in the cytoplasm of hair cells, while ERalpha was
      identified in the nuclei of hair cells and of underlying supporting cells. Double
      labeled preparations confirmed the extensive co-localization of aromatase and
      ERalpha in the vast majority of the hair cells. These results are consistent with
      studies on non-avian species, suggesting a role for estrogens in auditory
      function. These findings are also consistent with the notion that estrogens may
      contribute to a sex difference in hearing. To our knowledge, this is the first
      demonstration of the presence of aromatase and of the co-localization of
      aromatase and ERalpha in the sensory epithelium of the inner ear in any animal
      model.

PMID- 19397968
TI  - Hepatitis from Greater celandine (Chelidonium majus L.): review of literature and
      report of a new case.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Folk medicine is a rich source of useful
      therapeutic tools. Nevertheless, use of medicinal plants can have unwanted,
      negative effects. By means of the description of an adverse reaction to a herbal
      remedy, we highlight the need for better efficacy-toxicity studies on these
      products. AIM OF THE STUDY: To report a case of possible Chelidonium majus L.
      (Greater celandine)-induced hepatitis and evaluate the past published cases.
      MATERIALS AND METHODS: We outlined the main features of hepatitis associated with
      use of Chelidonium majus by providing a review of cases reported and analysing in
      detail a new one. RESULTS: Several cases of acute hepatitis related to Greater
      celandine consumption were found in the literature. The assessment for causality
      using Naranjo probability scale showed a probable relationship between the liver
      injury and the consumption of Chelidonium majus in the case we described.
      CONCLUSIONS: Our case, along with the other ones reported in the literature,
      increases the concern about the safety of oral use of Chelidonium majus. Plants
      used in traditional medicine are not necessarily harmless. Customers and
      prescribers should be aware of this, especially when a herbal drug is used with
      therapeutic purposes in absence of reliable studies of clinical efficacy and
      benefit-risk assessment.

PMID- 19397969
TI  - Subchronic toxicity and plasma pharmacokinetic studies on wogonin, a natural
      flavonoid, in Beagle dogs.
AB  - AIM OF THE STUDY: To investigate subchronic toxicity and pharmacokinetic of
      wogonin using Beagle dog and to provide foundation for clinical applications of
      this promising anticancer agent. MATERIALS AND METHODS: Wogonin was administered
      via intravenous infusion at dosages of 60, 30 and 15 mg/kg per day for 90 days
      followed by subchronic toxicity studies including general body parameters,
      hematological, plasma biochemical, histopathological, and viscera examinations.
      Dogs were given single intravenous injection of 20mg/kg wogonin followed by
      pharmacokinetic parameters estimating. RESULTS: Dogs treated with wogonin showed
      no significant changes in organs compared with controls in the toxicological
      study. An innocuous dose was established to be 60 mg/kg, which was approximately
      38.5 (body surface area) times higher than the dose (50mg/60 kg) used for human
      trials. The area under concentration-time curve (AUC(infinity)) was estimated to
      be 2137.9+/-231.4 ngh/ml, while the elimination half-life (t(1/2)) was 1.51+/
      0.43 h in dogs treated with 20mg/kg wogonin. CONCLUSIONS: Wogonin offered a wide
      margin of safety and had no organ toxicity for a long time intravenous
      administration in dogs.

PMID- 19397970
TI  - Beneficial effects of Chinese prescription Kangen-karyu on diabetes associated
      with hyperlipidemia, advanced glycation endproducts, and oxidative stress in
      streptozotocin-induced diabetic rats.
AB  - AIM OF THE STUDY: In the present study, we investigated the effects of Kangen
      karyu, a traditional Chinese prescription comprising six herbs, on diabetes.
      MATERIALS AND METHODS: Kangen-karyu extract (50, 100, or 200mg/kg body weight)
      was administered to streptozotocin (STZ)-induced diabetic rats and serum and
      hepatic biochemical factors, and protein expressions associated with oxidative
      stress and advanced glycation endproduct (AGE) formation were measured. RESULTS:
      The oral administration of Kangen-karyu significantly ameliorated
      hypertriglyceridemia induced by STZ injection, while serum levels of glucose and
      total cholesterol were mildly affected. Kangen-karyu also markedly reduced the
      levels of AGEs and malondialdehyde (MDA), a lipid peroxide product used as an
      indicator of oxidative stress in both serum and hepatic tissue. In addition,
      Kangen-karyu dose-dependently lowered the expression levels of N(epsilon)
      (carboxymethyl) lysine, one of the major component of AGEs closely associated
      with the pathogenesis of diabetes and liver cirrhosis, and receptor for AGEs, as
      well as the expression levels of nuclear factor-kappaB, inducible nitric oxide
      synthase, and cyclooxygenase-2 (COX-2) associated with oxidative stress.
      Especially, MDA levels in both serum and hepatic tissue and COX-2 expression
      increased by STZ were recovered by Kangen-karyu (200mg/kg body weight) to normal
      levels. CONCLUSIONS: Kangen-karyu showed favorable effects on hypertriglycemia,
      AGE formation, and oxidative stress in STZ-treated rats, suggesting beneficial
      effects on diabetes, diabetic hepatopathy, and liver diseases such as cirrhosis,
      as well as cardiovascular and cerebrovascular diseases.

PMID- 19397971
TI  - The amelioration of streptozotocin diabetes-induced renal damage by Wu-Ling-San
      (Hoelen Five Herb Formula), a traditional Chinese prescription.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Wu-Ling-San (Hoelen Five Herb Formula) is a
      Chinese prescription used to promote water metabolism. AIM OF THE STUDY: The
      present study was undertaken to characterize the effects of Wu-Ling-San on
      diabetic nephropathy. MATERIALS AND METHODS: Streptozotocin (STZ)-diabetic rats
      were orally administrated with Wu-Ling-San (0.5, 1.5, 2.5 g/(kgday)) once a day
      for 10 weeks. Changes in the renal function related parameters in plasma and
      urine were analyzed at the end of 10-week administration. Kidney was isolated for
      pathology histology, immunohistochemistry staining and Western blot analyses.
      RESULTS: Wu-Ling-San (2.5 g/(kgday)) partially decreased the high plasma glucose
      level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-h
      urinary albumin excretion rate, creatinine clearance, and glomerular mesangial
      matrix expansion were ameliorated by Wu-Ling-San. The increased expression of
      nuclear factor-kB as well as transforming growth factor-beta(1) and the
      progressive accumulation of fibronectin in kidney of diabetic rats were
      attenuated by Wu-Ling-San. Not only the elevated levels of advanced glycation end
      products (AGEs) and mitochondrial thiobarbituric acid-reactive substance, but
      also the higher levels of N(epsilon)-(carboxymethyl)lysine and receptor for AGEs
      in kidney of diabetic rats were ameliorated by Wu-Ling-San. CONCLUSIONS: : Wu
      Ling-San possess an anti-diabetic property with plasma glucose lowering action
      accompanied with amelioration of glycation-mediated renal damage.

PMID- 19397972
TI  - Antibacterial and anticandidal screening of Tunisian Citrullus colocynthis
      Schrad. from Medenine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Resistance to current antibacterial drugs and the
      rise of opportunistic fungal infections are growing global concerns. Traditional
      medicine is a potential source of new antibacterials and antifungals. Citrullus
      colocynthis Schrad. (Cucurbitaceae) endemic in Southern Tunisia, is used in folk
      medicine against dermatological, gynaecological and pulmonary infections. AIM OF
      STUDY: To assess in vitro antibacterial and anticandidal activity of aqueous and
      diluted acetone extracts of Citrullus colocynthis Schrad. MIC and MBC/MFC were
      determined for plant organs at different maturation stages. MATERIALS AND
      METHODS: Citrullus colocynthis Schrad. was harvested and its identification was
      verified. Aqueous and diluted acetone extracts (from the plant's roots, stems,
      leaves and three maturation stages of its fruit and seeds) were screened for
      activity against Gram-negative and Gram-positive bacteria (Escherichia coli,
      Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis)-and
      various Candida spp. (Candida glabrata, Candida albicans, Candida parapsilosis
      and Candida kreusei). RESULTS: All extracts showed activity against all strains.
      The highest MICs and MBCs/MFCs were obtained from the fruit aqueous extracts (MIC
      0.10mg/ml against Candida albicans and Candida glabrata, 0.20mg/ml against
      Escherichia coli and Pseudomonas aeruginosa), lowest activity from the root
      extracts. CONCLUSIONS: Citrullus colocynthis Schrad. shows antibacterial and
      anticandidal properties. The folk medicinal use as a broad-spectrum antimicrobial
      agent is validated.

PMID- 19397973
TI  - Water extract of Rheum officinale Baill. induces apoptosis in human lung
      adenocarcinoma A549 and human breast cancer MCF-7 cell lines.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rheum officinale Baill. (Da Huang) is one of the
      herbs commonly used in traditional Chinese medicine formulae against cancer. The
      traditional decoction is similar to the water extract used in the present study.
      AIM OF THE STUDY: The water extract of Da Huang was investigated to see if it
      possesses anticancer effects through apoptotic pathways. MATERIALS AND METHODS:
      Human lung adenocarcinoma A549 and human breast cancer MCF-7 cell lines were
      treated with different concentrations of Da Huang water extract at different time
      intervals. Growth inhibition was detected by MTS [3-(4,5-dimethylthiazol-2-yl)-5
      (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] and colony formation
      assays; apoptosis was detected by cell morphologic analysis, DNA fragmentation
      analysis and COMET assay. RESULTS: Da Huang water extract was found to have
      significant growth inhibitory effects on both A549 and MCF-7 cell lines with
      IC(50) values 620+/-12.7 and 515+/-10.1 microg/ml, respectively. Growth
      inhibitory effects were dose- and time-dependent. A significant decrease in cell
      number, DNA fragmentation and single DNA strand breakages were observed in the Da
      Huang water extract treated A549 and MCF-7 cells. CONCLUSIONS: This suggests that
      the water extract of Da Huang exerts potential anticancer activity through growth
      inhibition and apoptosis on MCF-7 and A549 cells lines.

PMID- 19397974
TI  - Evaluation of the antinociceptive activity of extracts of Sonchus oleraceus L. in
      mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Sonchus oleraceus L. has been used to relieve
      pain in Brazilian folk medicine. AIM OF THE STUDY: Sonchus oleraceus L. has been
      used to relieve pain in Brazilian folk medicine. This study was conducted to
      establish the antinociceptive properties of hydroethanolic and dichloromethane
      extracts from aerial parts of Sonchus oleraceus in mice using chemical and
      thermal models of nociception. MATERIALS AND METHODS: The formalin, hot plate,
      and tail immersion tests as well as acetic acid-induced writhing were used to
      investigate the antinociceptive activity in mice. RESULTS: Given orally, the
      extracts at test doses of 30-300 mg/kg, produced significant inhibitions on
      chemical nociception induced by intraperitoneal acetic acid and subplantar
      formalin since decreased the number of writhing episodes and the time licking.
      Treatment with the extracts in the same doses produced a significant increase of
      the reaction time in tail immersion and in the hot plate test. The extracts
      administered at 300 mg/kg, p.o. had a stronger antinociceptive effect than
      indomethacin (5mg/kg, p.o.) and morphine (10mg/kg, p.o.). CONCLUSION: The
      extracts of Sonchus oleraceus markedly demonstrated antinociceptive action in
      mice, which supports previous claims of its traditional use.

PMID- 19397975
TI  - Assessing medicinal plants from South-Eastern Spain for potential anti
      inflammatory effects targeting nuclear factor-Kappa B and other pro-inflammatory
      mediators.
AB  - AIM OF THE STUDY: Identification of plants with anti-inflammatory activity can be
      successfully based on information gained through knowledge on their traditional
      use. This is particularly true for biodiversity-rich regions of the world such as
      the Mediterranean. While such approaches are often single target based, here we
      used a multitarget, cell-based approach focusing on the pro-inflammatory
      signaling cascade and especially the NF-kappaB (NF-kappaB) pathway. MATERIALS AND
      METHODS: The plants from South-Eastern Spain were chosen on the basis that they
      were recorded as having a traditional use against an indication related to
      inflammation. The primary target was the transcription factor NF-kappaB (using a
      luciferase-based assay in HeLa cells). In addition extracts were tested in vitro
      for effects on cytokines (IL-6, IL-8, TNF-alpha) or PGE(2) in monocytes and for
      potential cytotoxic/pro-apoptotic action as well as for their influence on the
      cell cycle. RESULTS: Overall, 64 medicinal plant drugs from 61 species were
      assessed as potential inhibitors of inflammatory mediators to levels of 100-10
      microg/ml. Three plants showed the highest level of activity (50 microg/ml) in
      inhibiting the activation of NF-kappaB in 5.1 cells: Helichrysum stoechas
      (Asteraceae), Dorycnium pentaphyllum (Fabaceae, s.l.) and Phlomis almeriensis
      (Lamiaceae). In the tests against the cytokines it was particularly striking to
      find that a number of species, Bupleurum fruticosum, Chamaespartium tridentatum,
      Genista ramosissima, Helichrysum stoechas, Mercurialis tomentosa, Ononis
      ramosissima, Peganum harmala, Picnomon acarna, Retama sphaerocarpa and Santolina
      viscosa showed extracts that were active at inhibiting TNF-alpha (10 microg/ml).
      CONCLUSIONS: Overall, this project has identified a series of species with an
      activity profile which merits further phytochemical-pharmacological
      investigation.

PMID- 19397976
TI  - Antihyperlipidemic effect of the methanolic extract from Lagenaria siceraria
      Stand. fruit in hyperlipidemic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lagenaria siceraria Stand. (Cucurbitaceae) fruits
      have been used, traditionally, in the treatment of hyperlipidemia and
      atherosclerotic impasse and considered as cardioprotective and cardiotonic drug.
      AIM OF THE STUDY: The present work was undertaken to investigate the effects of
      methanolic extract from Lagenaria siceraria in experimentally induced
      hyperlipidemia in rats. MATERIALS AND METHODS: Methanolic extract of Lagenaria
      siceraria fruits (LSFE) (100, 200 and 300 mg/kg; p.o.) was administered to the
      high fat-diet-induced hyperlipidemic rats for 30 days to evaluate its
      antihyperlipidemic activity. Atorvastatin (10mg/kg; p.o.) was used as a standard
      drug. RESULTS: At the 30 th day, most significant reduction in lipid levels in
      the LSFE treated rats as compared to the rats fed with high-fat diet at the 0th
      day were: total cholesterol 290.14+/-18.42 mg/dl vs. 228.58+/-16.38 mg/dl, low
      density lipoprotein cholesterol 195.14+/-8.86 mg/dl vs. 120.57+/-8.11 mg/dl,
      triglyceride 232.41+/-15.22 mg/dl vs. 181.79+/-15.68 mg/dl, very low-density
      lipoprotein cholesterol 46.48+/-3.04 mg/dl vs. 36.35+/-3.13 mg/dl (P<0.0001).
      Conversely, high-density lipoprotein cholesterol levels were significantly
      (P<0.0001) increased from 48.52+/-6.52 to 71.66+/-5.14 mg/dl. The increase in
      weight in rats administered with LSFE was less when compared to rats fed with
      high-fat diet. Moreover, LSFE also exhibited significant increase in excretion of
      bile acids. CONCLUSION: The results demonstrate that the LSFE has a definite
      antihyperlipidemic potential. There is also a valid scientific basis for
      consuming it in the treatment of coronary artery diseases in India.

PMID- 19397977
TI  - Antinociceptive and anti-inflammatory kaempferol glycosides from Sedum
      dendroideum.
AB  - AIM OF THE STUDY: To identify the compounds responsible for the antinociceptive
      and anti-inflammatory effects previously described for Sedum dendroideum, through
      bioassay-guided fractionation procedures. MATERIALS AND METHODS: Antinociceptive
      activity was evaluated through mouse acetic acid-induced writhing model. The anti
      inflammatory activity was assessed through croton oil-induced mouse ear oedema
      and carrageenan-induced peritonitis. RESULTS: The Sedum dendroideum juice
      afforded seven known flavonoids identified with basis on NMR data. The oral
      administration of the major kaempferol glycosides kaempferitrin [1] (17.29
      micromol/kg), kaempferol 3-O-beta-glucopyranoside-7-O-alpha-rhamnopyranoside [2]
      (16.82 micromol/kg), kaempferol 3-O-neohesperidoside-7-O-alpha-rhamnopyranoside
      [3] (13.50 micromol/kg) or alpha-rhamnoisorobin [5] (23.13 micromol/kg) inhibited
      by 47.3%, 25.7%, 60.2% and 58.0%, respectively, the acetic acid-induced
      nociception (indomethacin: 27.95 micromol/kg, p.o.; 68.9%). Flavonoids 1, 2, 3 or
      5, at the same doses, reduced by 39.5%, 46.5%, 35.6% and 33.3%, respectively, the
      croton oil-induced oedema (dexamethasone: 5.09 micromol/kg, s.c.; 83.7%) and
      impaired leukocyte migration by 42.9%, 46.3%, 50.4% and 49.6%, respectively
      (dexamethasone: 5.09 micromol/kg, s.c.; 66.1%). CONCLUSIONS: Our findings show
      that the major kaempferol glycosides may account for the renowned medicinal use
      of Sedum dendroideum against pain and inflammatory troubles.

PMID- 19397978
TI  - Anti-hypoxic activity of the ethanol extract from Portulaca oleracea in mice.
AB  - AIM OF THE STUDY: To investigate the effects of the ethanol extract from
      Portulaca oleracea (EEPO) on hypoxia models mice and to find the possible
      mechanism of its anti-hypoxic actions so as to elucidate the anti-hypoxia
      activity and provide scientific basis for the clinical use of Portulaca oleracea.
      MATERIALS AND METHODS: EEPO was evaluated on anti-hypoxic activity in several
      hypoxia mice models, including closed normobaric hypoxia and sodium nitrite or
      potassium cyanide toxicosis. To verify the possible mechanism(s), we detected the
      activities of pyruvate kinase (PK), phosphofructokinase (PFK), lactate
      dehydrogenase (LDH) and the level of adenosine triphosphate (ATP) in mice
      cortices. RESULTS: Given orally, the EEPO at doses of 100, 200, 400 mg/kg could
      dose-dependently enhance the survival time of mice in both of the normobaric and
      chemical hypoxia models. The activity of the glycolysis enzymes and the level of
      ATP were higher than those of the control. In the pentobarbital sodium-induced
      sleeping time test and the open-field test, EEPO neither significantly enhanced
      the pentobarbital sodium-induced sleeping time nor impaired the motor
      performance, indicating that the observed anti-hypoxic activity was unlikely due
      to sedation or motor abnormality. CONCLUSIONS: These results demonstrated that
      the EEPO possessed notable anti-hypoxic activity, which might be related to
      promoting the activity of the key enzymes in glycolysis and improving the level
      of ATP in hypoxic mice.

PMID- 19397979
TI  - Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan
      constituents.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus niruri Linn. (Euphorbiaceae) is used
      as folk medicine in South America to treat excess uric acid. Our initial study
      showed that the methanol extract of Phyllanthus niruri and its lignans were able
      to reverse the plasma uric acid of hyperuricemic animals. AIM OF THE STUDY: The
      study was undertaken to investigate the mechanisms of antihyperuricemic effect of
      Phyllanthus niruri and its lignan constituents. MATERIAL AND METHODS: The
      mechanisms were investigated using xanthine oxidase assay and uricosuric studies
      in potassium oxonate- and uric acid-induced hyperuricemic rats. RESULTS:
      Phyllanthus niruri methanol extract exhibited in vitro xanthine oxidase
      inhibition with an IC50 of 39.39 microg/mL and a moderate in vivo xanthine
      oxidase inhibitory activity. However, the lignans display poor xanthine oxidase
      inhibition in vitro and a relatively weak in vivo inhibitory activity at 10mg/kg.
      On the other hand, intraperitoneal treatment with Phyllanthus niruri methanol
      extract showed 1.69 folds increase in urinary uric acid excretion when compared
      to the hyperuricemic control animals. Likewise, the lignans, phyllanthin,
      hypophyllanthin and phyltetralin exhibited up to 2.51 and 11.0 folds higher in
      urinary uric acid excretion and clearance, respectively. The co-administration of
      pyrazinamide with phyllanthin exhibited a significant suppression of
      phyllanthin's uricosuric activity resembling that of pyrazinamide with
      benzbromarone. CONCLUSIONS: The present study showed that the antihyperuricemic
      effect of Phyllanthus niruri methanol extract may be mainly due to its uricosuric
      action and partly through xanthine oxidase inhibition, whereas the
      antihyperuricemic effect of the lignans was attributed to their uricosuric
      action.

PMID- 19397980
TI  - Antidiabetic activities of Tecoma stans (L.) Juss. ex Kunth.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tecoma stans aqueous extract (TAE) is widely used
      as a traditional antidiabetic remedy in Mexico; its rational use is
      controversial. We provide evidence of its main antidiabetic activities. AIM OF
      THE STUDY: To evaluate in vivo and in vitro intestinal alpha-glucosidases
      inhibition as the possible mode of action of TAE on type 2 diabetes mellitus
      (DM2) animal models, and to test the effects of its sub-chronic administration on
      lipids and glucose blood levels. MATERIALS AND METHODS: In healthy and
      streptozotocin (STZ)-induced diabetic male Sprague-Dawley rats, glucose or
      cornstarch was administered after an oral dose of TAE, acarbose, tolbutamide or
      vehicle, in order to build starch and glucose tolerance curves (STC and GTC). An
      intestinal brush border preparation was used to evaluate the TAE alpha
      glucosidases inhibitory activity. Moreover, in STZ-induced diabetic rats TAE,
      tolbutamide or vehicle was administered for 21 days for evaluate their effects on
      fasting glucose cholesterol and triglycerides. Also, TAE total phenolic compounds
      were quantified. RESULTS: In STC, TAE decreased hyperglycemic peak values in both
      healthy and STZ-treated rats, in a magnitude similar to that of acarbose. The in
      vitro preparation showed a dose-dependent inhibition of glucose release from
      starch. Sub-chronic administration of TAE significantly reduced cholesterol and
      triglycerides levels. Moreover, we confirmed that acute and sub-chronic
      administration of TAE (500mg/kg) in both rat models did not diminish fasting
      glucose and did not modify the GTC. CONCLUSIONS: The study present evidence that
      the main antidiabetic effect of TAE is due to intestinal alpha-glucosidase
      inhibition by decreasing the postprandial hyper-glycaemia peak; in addition, TAE
      sub-chronic administration reduces triglycerides and cholesterol, without
      modifying fasting glucose.

PMID- 19397981
TI  - Cinchonain Ib isolated from Eriobotrya japonica induces insulin secretion in
      vitro and in vivo.
AB  - AIMS OF THE STUDY: Eriobotrya japonica leaves had been used traditionally for the
      treatment of diabetes mellitus by immersing the dried leaves in a hot water
      drink. Few studies have shown the hypoglycemic effect of Eriobotrya japonica
      using crude alcoholic extract and isolated methanolic compounds. These studies
      proposed that the mechanism of action could be by stimulating the beta-islets of
      Langerhans to secrete insulin, however with no scientific evidence. METHODS:
      Eriobotrya japonica water extract (EJWE) and the compounds derived from it:
      cinchonain Ib, procyanidin B-2, chlorogenic acid and epicatechin, were tested for
      their effects on insulin secretion from INS-1 cells and following oral
      administration in rats. RESULTS: The present study showed that EJWE increased
      significantly (p<0.05) insulin secretion from INS-1 cells in dose-dependent
      manner. Oral administration of EJWE at 230 mg/kg to rats, however, decreased
      plasma insulin level for as long as 240 min post-administration and caused a
      transient drop of blood glucose at 15 and 30 min post-administration. On the
      other hand, cinchonain Ib enhanced significantly (p<0.05) insulin secretion from
      INS-1 cells, whereas epicatechin inhibited significantly (p<0.05) insulin
      secretion from INS-1 cells. In addition, cinchonain Ib enhanced significantly
      (150%: p<0.05) plasma insulin level in rats for as long as 240 min after 108
      mg/kg oral administration but did not induce any change in blood glucose level.
      CONCLUSION: These data indicate that cinchonain Ib has an insulinotropic effect
      and suggest the possible use of cinchonain Ib for managing type 2 diabetes.

PMID- 19397982
TI  - Mutagenic and genotoxic effects of Baccharis dracunculifolia (D.C.).
AB  - Baccharis dracunculifolia (D.C.) (Asteraceae), a native plant to Brazil known as
      "vassourinha" or "alecrim-do-campo", is the most important botanical source of a
      Brazilian propolis called green propolis. The leaf extracts of this plant have
      been used to treat liver and digestive disorders. It has been recognized that
      green propolis can induce mutagenic effects at high doses, but no study reporting
      possible mutagenic effects by Baccharis dracunculifolia extracts in the maximum
      tolerated dose has been conducted. The aim of the present study was to
      investigate the genotoxic and mutagenic effects of this plant in vivo. Adult CF-1
      mice were treated with 0.5g/kg, 1.0g/kg or 2.0g/kg of an aqueous extract of
      Baccharis dracunculifolia by gavage for 3 consecutive days. Blood and liver
      samples were collected to detect DNA damage using the comet assay, while bone
      marrow samples were used to assess chromosome mutations by the micronucleus test.
      The extract increased the DNA damage in blood and liver tissues and the frequency
      of micronucleus in bone marrow. These findings suggest genotoxic and mutagenic
      effects of Baccharis dracunculifolia comparable to green propolis in mice.

PMID- 19397983
TI  - Anxiolytic-like effect of Sonchus oleraceus L. in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Sonchus oleraceus L. has been used as a general
      tonic in Brazilian folk medicine. Nevertheless, available scientific information
      regarding this species is scarce; there are no reports related to its possible
      effect on the central nervous system. AIM OF THE STUDY: This study was conducted
      to establish the anxiolytic effect of extracts from the aerial parts of Sonchus
      oleraceus. MATERIALS AND METHODS: This study evaluated the effect of
      hydroethanolic and dichloromethane extracts of Sonchus oleraceus in mice
      submitted to the elevated plus-maze and open-field tests. Clonazepam was used as
      the standard drug. RESULTS: In the elevated plus-maze test, the Sonchus oleraceus
      extracts increased the percentage of open arm entries (P<0.05) and time spent in
      the open-arm portions of the maze (P<0.05). The extracts induce an anti
      thigmotactic effect, evidenced by increased locomotor activity into the central
      part of the open field set-up (P<0.05). The extracts administered at 30-300
      mg/kg, p.o. had a similar anxiolytic effect to clonazepam (0.5 mg/kg, p.o.).
      CONCLUSION: These data indicate that Sonchus oleraceus extract exerts an
      anxiolytic-like effect on mice.

PMID- 19397985
TI  - Protein tyrosine phosphatase 1B inhibitory by dammaranes from Vietnamese Giao-Co
      Lam tea.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gynostemma pentaphyllum (Thunb.) tea was used in
      Vietnamese folk medicine as anti-diabetic agent. AIM OF THE STUDY: This study was
      aimed to investigate the inhibitory activities of fractions and constituents
      isolated from Gynostemma pentaphyllum on protein tyrosine phosphatase 1B (PTP1B)
      since it has been proposed as a treatment therapy for type 2 diabetes and
      obesity. MATERIALS AND METHODS: The 70% EtOH extract, CHCl3 fraction, EtOAc
      fraction, BuOH fraction, and seven isolated dammarane triterpenes were evaluated
      for their inhibitory activity in protein phosphatase enzymes (PTP1B and VHR).
      RESULTS: CHCl3-soluble fraction showed a dose-dependent inhibitory activity of
      the PTP1B enzyme with the IC50 value of 30.5 microg/mL. Among seven tested
      compounds, compounds 6 showed the most potent PTP1B inhibitory activity with IC50
      value of 5.3+/-0.4 microM compared to a range 15.7-28.5 microM for the other six
      compounds. The inhibition mode of 6 was competitive toward p-NPP with a K(i)
      value of 2.8 microM. CONCLUSION: These study results suggested that the PTP1B
      inhibitory activity of these dammaranes may enable this plant to play an
      important role in the treatment of diabetes.

PMID- 19397984
TI  - Evaluation of wound healing activity of root of Mimosa pudica.
AB  - ETHNO PHARMACOLOGICAL RELEVANCE: Mimosa pudica, commonly known as touch-me-not,
      is used in folklore medicine in arresting bleeding and in skin diseases. AIM:
      There was no scientific evidence justifying the use of Mimosa pudica, therefore
      the present study was aimed at evaluation of wound healing activity of the plant.
      MATERIALS AND METHODS: In the present study the roots of Mimosa pudica were
      studied for wound healing activity by incorporating the methanolic and the total
      aqueous extract in simple ointment base B.P. in concentration of 0.5% (w/w), 1%
      (w/w) and 2% (w/w). Wound healing activity was studied in three types of model in
      rats viz. excision, incision and estimation of biochemical parameter. In case of
      the excision wound model wound contraction and period of epithelization was
      studied while in incision wound model was evaluated by determining tensile
      strength and hydroxyproline content in the scab. RESULTS: Treatment of wound with
      ointment containing 2% (w/w) the methanolic and 2% (w/w) the total aqueous
      extract exhibited significant (P<0.001) wound healing activity. The methanolic
      and total aqueous extracts were analyzed for total phenols content equivalent to
      Gallic acid. The content of total phenols was 11% (w/w) and 17% (w/w) in
      methanolic and total aqueous extract respectively. CONCLUSION: The methanolic
      extract exhibited good wound healing activity probably due to phenols
      constituents.

PMID- 19397986
TI  - In vitro antimicrobial activity of Caesalpinia ferrea Martius fruits against oral
      pathogens.
AB  - AIM: In the Amazon region of Brazil, the fruits of Caesalpinia ferrea Martius
      (Brazilian ironwood) are widely used as an antimicrobial and healing medicine in
      many situations including oral infections. This study aimed to evaluate the
      antimicrobial activity of Caesalpinia ferrea Martius fruit extract against oral
      pathogens. MATERIALS AND METHODS: Polyphenols estimation and spectral analysis
      ((1)H NMR) of the methanol extract were carried out. The microorganisms Candida
      albicans, Streptococcus mutans, Streptococcus salivarius, Streptococcus oralis
      and Lactobacillus casei were tested using the microdilution method for planktonic
      cells (MIC) and a multispecies biofilm model. Chlorhexidine was used as positive
      control. RESULTS: Polyphenols in the extract were estimated at 7.3% and (1)H NMR
      analysis revealed hydroxy phenols and methoxilated compounds. MIC values for
      Candida albicans, Streptococcus mutans, Streptococcus salivarius, Streptococcus
      oralis and Lactobacillus casei were 25.0, 40.0, 66.0, 100.0, 66.0 microg/mL,
      respectively. For the biofilm assay, chlorhexidine and plant extract showed no
      growth at 10(-4) and 10(-5) microbial dilution, respectively. At 10(-4) and 10(
      5) the growth values (mean+/-SD) of the negative controls (DMSO and saline
      solution) for Streptococcus mutans, Streptococcus sp. and Candida albicans were
      8.1+/-0.7, 7.0+/-0.6 and 5.9+/-0.9 x 10(6)CFU, respectively. CONCLUSION:
      Caesalpinia ferrea fruit extract can inhibit in vitro growth of oral pathogens in
      planktonic and biofilm models supporting its use for oral infections.

PMID- 19397987
TI  - Gastric antisecretory and antiulcer activities of Cyclea peltata (Lam.) Hook. f.
      & Thoms. in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cyclea peltata (Lam.) Hook. f. & Thoms.
      (Menispermaceae), locally called 'Padathaali/Padakizhangu' is used in Ayurvedic
      medicine to treat peptic ulcer. AIM OF THE STUDY: To evaluate the gastric
      antisecretory and antiulcer activity of Cyclea peltata. MATERIALS AND METHODS:
      The ethanolic extract of Cyclea peltata root was used to evaluate its gastric
      antisecretory and antiulcer effect in the pylorus-ligated rat model and gastric
      lesions induced by ethanol or ethanol and indomethacin respectively in rats. The
      levels of gastric wall mucus, non-protein sulfhydryl groups (NP-SH),
      malondialdehyde, protein and catalase activity in the stomach samples of Cyclea
      peltata treated and control groups of rats were also quantified. RESULTS: The
      ethanolic extract of Cyclea peltata roots showed significant antisecretory
      activity as evidenced by decreased pepsin secretion, gastric juice volume and
      acid output in pylorus-ligated rats. Pretreatment with Cyclea peltata extract
      provided significant protection against the peptic ulceration caused by ethanol
      administered individually, or in combination with indomethacin. Our studies also
      revealed that pretreatment with Cyclea peltata significantly increased the
      gastric protein and catalase concentration of ethanol treated rats. Further, it
      showed significant gastroprotective effects on the stomach wall of ethanol or
      ethanol and indomethacin treated rats by decreasing malondialdehyde level,
      increasing the gastric wall mucus and non-protein sulfhydryl groups. CONCLUSION:
      The present findings demonstrate that Cyclea peltata ethanolic extract has potent
      antisecretory and antiulcer effects and justify the traditional/ethnic usage of
      this herb to treat peptic ulcers and consequent stomach ache.

PMID- 19397988
TI  - Operational characteristics of a 1.2-MW biomass gasification and power generation
      plant.
AB  - In this study, we analyzed the operational characteristics of a 1.2-MW rice husk
      gasification and power generation plant located in Changxing, Zhejiang province,
      China. The influences of gasification temperature, equivalence ratio (ER),
      feeding rate and rice husk water content on the gasification characteristics in a
      fluidized bed gasifier were investigated. The axial temperature profile in the
      dense phase of the gasifier showed that inadequate fluidization occurred inside
      the bed, and that the temperature was closely related to changes in ER and
      feeding rate. The bed temperature increased linearly with increasing ER when the
      feeding rate was kept constant, while a higher feeding rate corresponded to a
      lower bed temperature at fixed ER. The gas heating value decreased with
      increasing temperature, while the feeding rate had little effect. When the
      gasification temperature was 700-800 degrees C, the gas heating value ranged from
      5450-6400 kJ/Nm(3). The water content of the rice husk had an obvious influence
      on the operation of the gasifier: increases in water content up to 15% resulted
      in increasing ER and gas yield, while water contents above 15% caused aberrant
      temperature fluctuations. The problems in this plant are discussed in the light
      of operational experience of MW-scale biomass gasification and power generation
      plants.

PMID- 19397989
TI  - Kinetic study of hydrolysis of xylan and agricultural wastes with hot liquid
      water.
AB  - We investigated the kinetics of hot liquid water (HLW) hydrolysis over a 60-min
      period using a self-designed setup. The reaction was performed within the range
      160-220 degrees C, under reaction conditions of 4.0 MPa, a 1:20 solid:liquid
      ratio (g/mL), at 500 rpm stirring speed. Xylan was chosen as a model compound for
      hemicelluloses, and two kinds of agricultural wastes-rice straw and palm shell
      were used as typical feedstocks representative of herbaceous and woody biomasses,
      respectively. The hydrolysis reactions for the three kinds of materials followed
      a first-order sequential kinetic model, and the hydrolysis activation energies
      were 65.58 kJ/mol for xylan, 68.76 kJ/mol for rice straw, and 95.19 kJ/mol for
      palm shell. The activation energies of sugar degradation were 147.21 kJ/mol for
      xylan, 47.08 kJ/mol for rice straw and 79.74 kJ/mol for palm shell. These
      differences may be due to differences in the composition and construction of the
      three kinds of materials. In order to reduce the decomposition of sugars, the
      hydrolysis time of biomasses such as rice straw and palm shell should be strictly
      controlled.

PMID- 19397990
TI  - Bioenergy research and development in China. Guest editorial.

PMID- 19397991
TI  - Systemic dissemination and cutaneous damage in a mouse model of staphylococcal
      skin infections.
AB  - Serious staphylococcal infections frequently begin in the skin. The present study
      used a mouse model of such infections to evaluate the ability of Staphylococcus
      aureus to disseminate from the skin and to determine if cutaneous damage from the
      infections was required for dissemination. The mice were inoculated with S.
      aureus onto flank skin prepared by a tape-stripping method that caused minimal
      disruption of the epidermal keratinocyte layers. After these inoculations the
      staphylococci were found to disseminate to the spleen and kidneys of almost all
      animals within 6h. Induction of leucopenia did not affect this process. Cutaneous
      damage was prominent in these experimental infections and included loss of the
      epidermis, neutrophil infiltration into the epidermis, and complete necrosis of
      the dermis. The latter also occurred in cyclophosphamide-treated animals,
      indicating that the organisms themselves and not the host inflammatory responses
      were responsible. Dermal necrosis did not develop until 48h after inoculation, a
      time by which dissemination had already occurred. Therefore, in this mouse model
      system S. aureus is capable of penetrating the epidermal keratinocyte layers and
      disseminating rapidly after inoculation; the experimental infections do produce
      significant dermal damage, but the latter develops after dissemination has
      already taken place.

PMID- 19397992
TI  - The Yersinia pseudotuberculosis YplA phospholipase differs in its activity,
      regulation and secretion from that of the Yersinia enterocolitica YplA.
AB  - Analysis of the Yersinia pseudotuberculosis and Yersinia pestis genomes indicates
      that both species carry an identical copy of a gene that is predicted to encode a
      protein which shares 80% similarity to the Yersinia enterocolitica YplA, a
      secreted phospholipase that has been shown to contribute to virulence. In
      contrast to well tolerated production of the Y. enterocolitica YplA in
      Escherichia coli, Y. pseudotuberculosis YplA expression was found to be toxic;
      however, cell viability could be restored if the Y. pseudotuberculosis YplA was
      expressed in the presence of its accessory protein YplB. In vitro, Y.
      pseudotuberculosis YplB was shown to reduce the activity of its cognate
      phospholipase in a dose-dependent manner. To determine whether the Y.
      pseudotuberculosis and Y. enterocolitica YplAs were secreted and regulated in a
      similar manner, secretion and promoter activity assays were performed. Unlike the
      situation apparent in Y. enterocolitica, expression of the Y. pseudotuberculosis
      yplA gene did not appear to be controlled by the flagellar regulon, nor did the
      phospholipase appear to be efficiently exported through the flagellar apparatus.
      These results indicate that the Yersinia YplAs vary in many of their attributes
      despite their high degree of amino acid homology.

PMID- 19397993
TI  - The role of respiratory donor enzymes in Campylobacter jejuni host colonization
      and physiology.
AB  - The human pathogen Campylobacter jejuni utilizes oxidative phosphorylation to
      meet all of its energy demands. The genome sequence of this bacterium encodes a
      number of respiratory enzymes in a branched electron transport chain that
      predicts the utilization of a number of electron transport chain donor and
      acceptor molecules. Three of these electron donor enzymes: hydrogenase, formate
      dehydrogenase, and 2-oxoglutarate:acceptor oxidoreductase (OOR), oxidize
      hydrogen, formate and alpha-ketoglutarate as electron donors, respectively.
      Mutations were created in these donor enzymes to isolate mutants in hydrogenase
      (HydB::CM), formate dehydrogenase (Fdh::CM), and OOR (OorB::CM), as well as a
      strain with insertions in both hydrogenase and formate dehydrogenase (Hyd::Fdh).
      These mutants are deficient in their respective enzyme activities and do not
      reduce the components of the electron transport chain when provided with their
      respective substrates. The presence of either hydrogen or formate in the media
      stimulated the growth of wild type (WT) C. jejuni (but not the associated mutant
      strains) and at least one of these alternative substrates is required for growth
      of the OOR mutant strain OorB::CM. Finally, the importance of hydrogenase,
      formate dehydrogenase and OOR as well as the complex I of C. jejuni are
      elucidated by chicken colonization assays, where the double mutant Hyd::Fdh,
      OorB::CM and nuo mutants are severely impaired in host colonization.

PMID- 19397994
TI  - Cytotoxicity of flavones and flavonols to a human esophageal squamous cell
      carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis.
AB  - In this study, cytotoxic effects of structurally related flavones and flavonols
      on a human esophageal squamous cell carcinoma cell line (KYSE-510) were
      determined, and the molecular mechanisms responsible for their cytotoxic effects
      were studied. The results of MTT assay showed that flavones (luteolin, apigenin,
      chrysin) and flavonols (quercetin, kaempferol, myricetin) were able to induce
      cytotoxicity in KYSE-510 cells in a dose- and time-dependent manner, and the
      cytotoxic potency of these compounds was in the order of:
      luteolin>quercetin>chrysin>kaempferol>apigenin>myricetin. Flow cytometry and DNA
      fragmentation analysis indicated that the cytotoxicity induced by flavones and
      flavonols was mediated by G(2)/M cell cycle arrest and apoptosis. Furthermore,
      the expression of genes related to cell cycle arrest and apoptosis was assessed
      by oligonucleotide microarray, real-time RT-PCR and Western blot. It was shown
      that the treatment of KYSE-510 cells with these compounds caused G(2)/M arrest
      through up-regulation of p21(waf1) and down-regulation of cyclin B1 at the mRNA
      and protein levels, and induced p53-independent mitochondrial-mediated apoptosis
      through up-regulation of PIG3 and cleavage of caspase-9 and caspase-3. The
      results of western blot analysis further showed that increases of p63 and p73
      protein translation or stability might be contributed to the regulation of
      p21(waf1), cyclin B1 and PIG3.

PMID- 19397995
TI  - Reliable size determination of nanoparticles using dynamic light scattering
      method for in vitro toxicology assessment.
AB  - Dynamic light scattering (DLS) is widely used for the evaluation of the particle
      size in the toxicity assessment of nanoparticles. However, the many types of DLS
      instruments and analytical procedures sometimes give different apparent sizes of
      particles and make it complicated to understand the size dependence on particles
      for the toxicity assay. In this study, we established an evaluation method of
      secondary nanoparticle sizes using a DLS analysis. First, we established a
      practical method for determining size with an appropriate evaluation of
      uncertainties. This proposed method could be a universal protocol for toxicity
      assessment that would allow researchers to achieve some degree of concordance on
      the size of nanoparticles for an assessment. Second, we investigated the
      processes associated with particles in suspension by examining the changes in the
      size and the light scattering intensity of secondary nanoparticles during an in
      vitro toxicity assessment, since the transport mode of particles to cells is
      significant in understanding in vitro nano-toxicity. In this study, these two
      points were investigated on TiO(2) nanoparticles suspension as an example. The
      secondary particles of TiO(2) with a light scattering intensity-averaged diameter
      (d(l)) of 150-250 nm were characterized with appropriate uncertainties. The sizes
      were found to be comparable with values determined using other analytical
      procedures and other instruments. It is suggested that d(l) could be an effective
      size parameter for toxicity assessments. Furthermore, TiO(2) secondary
      nanoparticle suspensions are well dispersed with slow gravity settling, no
      agglomeration, with the diffusion process as the primary transport mode of
      particles to cells.

PMID- 19397996
TI  - Use of IL-18 production in a human keratinocyte cell line to discriminate contact
      sensitizers from irritants and low molecular weight respiratory allergens.
AB  - Assessment of allergenic potential of chemicals is performed using animal models,
      such as the murine local lymph node assay, which does not distinguish between
      respiratory and contact allergens. Progress in understanding the mechanisms of
      skin sensitization, provides us with the opportunity to develop in vitro tests as
      an alternative to in vivo sensitization testing. The aim of the present study was
      to evaluate the possibility to use intracellular interleukin-18 (IL-18)
      production to assess in vitro the contact sensitization potential of low
      molecular weight chemicals. The human keratinocyte cell line NCTC2455 was used.
      Cells were exposed to contact allergens (cinnamaldehyde, dinitrochlorobenzene,
      glyoxal, isoeugenol, p-phenylediamine, resorcinol, tetramethylthiuram disulfide,
      2-mercaptobenzothiazole, 4-nitrobenzylbromide), to proaptens (cinnamyl alcohol,
      eugenol), to respiratory allergens (diphenylmethane diisocyanate, trimellitic
      anhydride, ammonium hexachloroplatinate) and to irritants (sodium lauryl
      sulphate, salicylic acid, phenol). Cell associated IL-18 were evaluated 24 later.
      At not cytotoxic concentrations (cell viability higher of 75%, as assessed by MTT
      reduction assay), all contact sensitizers, including proaptens, induced a dose
      related increase in IL-18, whereas both irritants and respiratory failed. Similar
      results were also obtained using primary human keratinocytes. Results were
      reproducible, and the method could be transferred to another laboratory,
      suggesting the potential use of the test in immunotoxicity testing strategies.
      Overall, results obtained indicated that cell-associated IL-18 may provide an in
      vitro tool for identification and discrimination of contact versus respiratory
      allergens and/or irritants.

PMID- 19397997
TI  - Juvenile toxicity of cyclosporin in the rat.
AB  - The pups from 32 litters of SD rats were given 0, 1, 3 or 10mg/kg-d of
      cyclosporin by oral gavage from 4 to 28 days of age. 10mg/kg-d resulted in a
      persistent impairment of the primary antibody response at 10 weeks of age.
      Indications of systemic toxicity, including the death of 10/64 pups and severely
      depressed weight gain, were also observed at this dose level. Arteriopathy of the
      heart and tubular basophilia and edema in the cortico-medullary region of the
      kidney were observed at 3 and 10mg/kg-d. In conclusion, while pharmacological
      effects were seen at all dose levels, the adverse effects of cyclosporin on the
      development of the immune system in the rat only occurred at a dose level that
      also induced systemic toxicity.

PMID- 19397998
TI  - Assessment of developmental effects of hypothyroidism in rats from in utero and
      lactation exposure to anti-thyroid agents.
AB  - To clarify the developmental effects of hypothyroidism and to establish a
      detection system of resultant brain retardation, pregnant rats were administered
      3 or 12 ppm of 6-propyl-2-thiouracil (PTU) or 200 ppm of methimazole (MMI) in the
      drinking water from gestation day 10 to postnatal day 20 and maintained after
      weaning until 11 weeks of age (adult stage). Offspring displayed evidence of
      growth retardation lasting into the adult stage, which was particularly prominent
      in males. Except for hypothyroidism-related thyroid follicular cell hypertrophy,
      most histopathological changes that appeared at the end of chemical exposure were
      related to growth retardation and reversed by the adult stage. A delayed onset of
      puberty and an adult stage gonadal enlargement occurred by exposure to anti
      thyroid agents, both being especially evident in males, and this effect might be
      related to gonadal growth suppression during exposure. At the adult stage, the
      distribution variability of hippocampal CA1 pyramidal neurons reflecting
      mismigration could be detected in animals receiving both thyrotoxins, with a dose
      dependent effect by PTU. Similarly, a reduction in the area of the corpus
      callosum and oligodendroglial cell numbers in the cerebral deep cortex, both
      reflecting impaired oligodendroglial development, were detected in rats
      administered both chemicals. Thus, all effects, except for impaired brain
      development, might be linked to systemic growth retardation, and the brain
      morphometric methods employed in this study may be useful to evaluate the potency
      of chemicals to induce hypothyroidism-related brain retardation.

PMID- 19398000
TI  - Matrix metalloproteinase-1 cleavage site recognition and binding in full-length
      human type III collagen.
AB  - Matrix metalloproteinases (MMPs) are essential for normal collagen turnover,
      recovery from fibrosis, and vascular permeability. In fibrillar collagens, MMP-1,
      MMP-8, and MMP-13 cleave a specific glycine-isoleucine or glycine-leucine bond,
      despite the presence of this sequence in other parts of the protein. This cut
      site specificity has been hypothesized to arise from a unique, relaxed super
      secondary structure in this area due to local hydroxyproline poor character. In
      this study we examined the mechanism of interaction and cleavage of human type
      III collagen by fibroblast MMP-1 by using a panel of recombinant human type III
      collagens (rhCIIIs) containing engineered sequences in the vicinity of the
      cleavage site. Native and recombinant type III collagens had similar biochemical
      and structural characteristics, as indicated by transmission electron microscopy,
      circular dichroism spectropolarimetry, melting temperature and hydroxyproline
      analysis. A single amino acid change at the I785 cleavage site to proline
      resulted in partial MMP-1 resistance, but cuts were found in novel sites in the
      original cleavage region. However, the replacement of five Y-position residues by
      proline in this region, regardless of I785 variation, conferred complete
      resistance to MMP-1, MMP-8, MMP-13, trypsin, and elastase. MMP-1 had a decreased
      specific activity towards and reduced cleavage rate of rhCIII I785P but a K(m)
      similar to wild-type. Despite the reductions in protease sensitivity, MMP-1 bound
      to all of the engineered rhCIIIs with comparable affinity, indicating that MMP-1
      binding is not sufficient for cleavage. The relaxed tertiary structure in the MMP
      cleavage region may permit local collagen unwinding by MMP-1 that enables site
      specific proteolysis.

PMID- 19397999
TI  - Increase in thiol oxidative stress via glutathione reductase inhibition as a
      novel approach to enhance cancer sensitivity to X-ray irradiation.
AB  - Depletion of the reduced form of glutathione (GSH) has been extensively studied
      for its effect on sensitizing cancer to radiation. However, little is known about
      the effects of thiol oxidative stress created through an increase in glutathione
      disulfide (GSSG) on cancer sensitivity to radiation. In this study, an increase
      in GSSG was effectively created using 2-acetylamino-3-[4-(2-acetylamino-2
      carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid
      (2-AAPA), an irreversible glutathione reductase (GR) inhibitor. Our results
      demonstrate that the GSSG increase significantly enhanced cancer sensitivity to X
      ray irradiation in four human cancer cell lines (A431, MCF7, NCI-H226, and OVCAR
      3). When cells were pretreated with 2-AAPA followed by X-ray irradiation, the
      IC(50) values for X-ray irradiation of A431, MCF7, NCI-H226, and OVCAR-3 cells
      were reduced, from 24.2 +/- 2.8, 42.5 +/- 3.0, 43.0 +/- 3.6, and 27.8+/-3.5 Gy to
      6.75 +/- 0.9, 8.1 +/- 1.1, 6.75 +/- 1.0, and 12.1 +/- 1.7 Gy, respectively. The
      synergistic effects observed from the combination of X-rays plus 2-AAPA were
      comparable to those from the combination of X-rays plus buthionine sulfoximine, a
      reference compound known to increase cancer sensitivity to radiation. The
      synergistic effect was correlated with an increase in cell thiol oxidative
      stress, which was reflected by a five-to sixfold increase in GSSG and 25%
      increase in total disulfides. No change in GSH or total thiols was observed as a
      result of GR inhibition.

PMID- 19398001
TI  - Clinical rejection and persistent immune regulation in kidney transplant
      patients.
AB  - We evaluated whether the regulatory function of CD4(+)CD25(high+)FoxP3(+) T-cells
      from patients on tacrolimus and mycophenolate mofetil (MMF) is affected by
      preceding steroid and anti-CD25 mAb induction therapy and whether this function
      is associated with rejection after kidney transplantation. Kidney recipients
      (N=15) were randomized to receive either anti-CD25 mAb induction (i.e.,
      daclizumab) or steroids for 4 months. We analyzed the presence and suppressive
      activity of CD4(+)CD25(high+)FoxP3(+) peripheral T-cells in samples obtained at
      pre and 4-6 months after transplantation. Anti-CD25 mAb therapy and treatment
      with steroids did not significantly affect protein expression of FoxP3. However,
      at the functional level, significant differences were found in the regulatory
      activities of CD4(+)CD25(high+) T-cells from the anti-CD25 group vs those from
      the steroid group. At 4-6 months after transplantation, the regulatory activities
      of CD4(+)CD25(high+) T-cells were comparable to those before anti-CD25 mAb
      therapy; 49+/-13% (mean+/-SEM) vs 40+/-14% at a 1:20 ratio (CD25(high+):CD25(
      /dim)), respectively. In contrast, the regulatory capacities of CD(+)D25(bright+)
      T-cells from the steroid patient group became significantly impaired. The
      percentage inhibition of the anti-donor response decreased from 57+/-12% before
      transplantation to 12+/-7% after transplantation (p<0.01). Five out of 15
      patients experienced a rejection episode. At 4-6 months after transplantation,
      the CD25(high+) cells from these rejectors (who all received daclizumab induction
      therapy) had clear regulatory function, while suppression by CD25(high+) cells
      from non-rejectors (N=10) was significantly lower. The percentage inhibition of
      the anti-donor response was 48+/-14% (mean+/-SEM) vs 10+/-7%, respectively,
      p=0.02. Anti-CD25 mAb induction therapy does not negatively influence the
      regulatory function of CD4(+)CD25(high+)FoxP3(+) T-cells from kidney transplant
      recipients on tacrolimus and MMF. The majority of these patients experienced an
      acute rejection episode, which suggests that immune activation is required for
      persistent immunoregulatory function.

PMID- 19398002
TI  - Endocytosis controls glutamate-induced nuclear accumulation of ERK.
AB  - Nuclear translocation of activated extracellular signal-regulated kinases (ERK)
      in neurons is critical for gene regulations underlying long-term neuronal
      adaptation and memory formation. However, it is unknown how activated ERK travel
      from the post-synaptic elements where their activation occurs, to the nucleus
      where they translocate to exert their transcriptional roles. In cultured neurons,
      we identified endocytosis as a prime event in glutamate-induced nuclear
      trafficking of ERK2. We show that glutamate triggers a rapid recruitment of ERK2
      to a protein complex comprising markers of the clathrin-dependent endocytotic and
      AMPA/glutamate receptor subtype. Inhibition of endocytosis results in a neuritic
      withholding of activated ERK2 without modification of ERK2 activity. As a
      consequence, endocytosis blockade alters ERK-dependent nuclear events, such as
      mitogen and stressed-activated kinase-1 (MSK-1) activation, histone H3
      phosphorylation and gene regulations. Our data provide the first evidence that
      the endocytic pathway controls ERK nuclear translocation and ERK-dependent gene
      regulations induced by glutamate.

PMID- 19398003
TI  - Targeted gene disruption in Francisella tularensis by group II introns.
AB  - Francisella tularensis is a highly infectious Gram-negative bacterium that is the
      causative agent of tularemia. Very little is known about the molecular mechanisms
      responsible for F. tularensis virulence, in part due to the paucity of genetic
      tools available for the study of F. tularensis. We have developed a gene knockout
      system for F. tularensis that utilizes retargeted mobile group II introns, or
      "targetrons". These targetrons disrupt both single and duplicated target genes at
      high efficiency in three different F. tularensis subspecies. Here we describe in
      detail the targetron-based method for insertional mutagenesis of F. tularensis
      genes, which should facilitate a better understanding of F. tularensis
      pathogenesis. Group II introns can be adapted to inactivate genes in bacteria for
      which few genetic tools exist, thus providing a powerful tool to study the
      genetic basis of bacterial pathogenesis.

PMID- 19398004
TI  - Genetic analysis of P-TEFb function via heterologous nucleic acid tethering
      systems.
AB  - Recent global genetic analyses demonstrated that the regulation of gene
      expression at the level of transcription elongation is a common feature in
      eukaryotes. The positive transcription elongation factor P-TEFb plays a critical
      role in this process. P-TEFb is a cyclin-dependent kinase, which controls the
      fraction of RNA polymerase II (RNAP II) that can enter productive elongation.
      While the biochemical properties of P-TEFb and its associated factors have been
      characterized extensively in vitro, its function in vivo remains less well
      understood. In this paper, we describe various heterologous nucleic acid
      tethering systems that can be used to examine transcription factors that function
      via P-TEFb.

PMID- 19398005
TI  - Millisecond phase kinetic analysis of elongation catalyzed by human, yeast, and
      Escherichia coli RNA polymerase.
AB  - Strategies for assembly and analysis of human, yeast, and bacterial RNA
      polymerase elongation complexes are described, and methods are shown for
      millisecond phase kinetic analyses of elongation using rapid chemical quench
      flow. Human, yeast, and bacterial RNA polymerases function very similarly in NTP
      Mg2+ commitment and phosphodiester bond formation. A "running start, two-bond,
      double-quench" protocol is described and its advantages discussed. These studies
      provide information about stable NTP-Mg2+ loading, phosphodiester bond synthesis,
      the processive transition between bonds, and sequence-specific effects on
      transcription elongation dynamics.

PMID- 19398006
TI  - Affinity purification of ribosomes to access the translatome.
AB  - We describe ribosome affinity purification (RAP), a method that allows rapid
      purification of ribosomes and associated messages from the yeast Saccharomyces
      cerevisiae. The method relies on the expression of protein A tagged versions of
      the ribosomal protein Rpl16, which is used to efficiently recover endogenously
      formed ribosomes and polysomes from cellular extracts with IgG-coupled spherical
      microbeads. This approach can be applied to profile reactions of the translatome,
      which refers to all messages associated with ribosomes, with those of the
      transcriptome using DNA microarrays. In addition, ribosomal proteins, their
      modifications, and/or other associated proteins can be mapped with mass
      spectrometry. Finally, application of this method in other organisms provides a
      valuable tool to decipher cell-type specific gene expression patterns.

PMID- 19398007
TI  - Generating mutant rats using the Sleeping Beauty transposon system.
AB  - The laboratory rat is an invaluable animal model for biomedical research.
      However, mutant rat resource is still limited, and development of methods for
      large-scale generation of mutants is anticipated. We recently utilized the
      Sleeping Beauty (SB) transposon system to develop a rapid method for generating
      insertional mutant rats. Firstly, transgenic rats carrying single transgenes,
      namely the SB transposon vector and SB transposase, were generated. Secondly,
      these single transgenic rats were interbred to obtain doubly-transgenic rats
      carrying both transgenes. The SB transposon was mobilized in the germline of
      these doubly-transgenic rats, reinserted into another location in the genome and
      heterozygous mutant rats were obtained in the progeny. Gene insertion events were
      rapidly and non-invasively identified by the green fluorescence protein (GFP)
      reporter incorporated in the transposon vector, which utilizes a polyA-trap
      approach. Mutated genes were confirmed by either linker ligation-mediated PCR or
      3'-rapid amplification of cDNA ends (3'RACE). Endogenous expression profile of
      the mutated gene can also be visualized using the LacZ gene incorporated as a
      promoter-trap unit in the transposon vector. This method is straightforward,
      readily applicable to other transposon systems, and will be a valuable mutant rat
      resource to the biomedical research community.

PMID- 19398009
TI  - Constraint counting on RNA structures: linking flexibility and function.
AB  - RNA structures are highly flexible biomolecules that can undergo dramatic
      conformational changes required to fulfill their diverse functional roles.
      Constraint counting on a topological network representation of an RNA structure
      can provide very efficiently detailed insights into the intrinsic flexibility
      characteristics of the biomolecule. In the network, vertices represent atoms and
      edges represent covalent and strong non-covalent bonds and angle constraints.
      Initially, the method has been successfully applied to identify rigid and
      flexible regions in proteins. Here, we present recent progress in extending the
      approach to RNA structures. As a case study, we analyze stability characteristics
      of the ribosomal exit tunnel and relate these findings to the tunnel's active
      role in co-translational processes.

PMID- 19398008
TI  - Theoretical studies of RNA catalysis: hybrid QM/MM methods and their comparison
      with MD and QM.
AB  - Hybrid QM/MM methods combine the rigor of quantum mechanical (QM) calculations
      with the low computational cost of empirical molecular mechanical (MM) treatment
      allowing to capture dynamic properties to probe critical atomistic details of
      enzyme reactions. Catalysis by RNA enzymes (ribozymes) has only recently begun to
      be addressed with QM/MM approaches and is thus still a field under development.
      This review surveys methodology as well as recent advances in QM/MM applications
      to RNA mechanisms, including those of the HDV, hairpin, and hammerhead ribozymes,
      as well as the ribosome. We compare and correlate QM/MM results with those from
      QM and/or molecular dynamics (MD) simulations, and discuss scope and limitations
      with a critical eye on current shortcomings in available methodologies and
      computer resources. We thus hope to foster mutual appreciation and facilitate
      collaboration between experimentalists and theorists to jointly advance our
      understanding of RNA catalysis at an atomistic level.

PMID- 19398010
TI  - Molecular dynamics flexible fitting: a practical guide to combine cryo-electron
      microscopy and X-ray crystallography.
AB  - Hybrid computational methods for combining structural data from different sources
      and resolutions are becoming an essential part of structural biology, especially
      as the field moves toward the study of large macromolecular assemblies. We have
      developed the molecular dynamics flexible fitting (MDFF) method for combining
      high-resolution atomic structures with cryo-electron microscopy (cryo-EM) maps,
      that results in atomic models representing the conformational state captured by
      cryo-EM. The method has been applied successfully to the ribosome, a
      ribonucleoprotein complex responsible for protein synthesis. MDFF involves a
      molecular dynamics simulation in which a guiding potential, based on the cryo-EM
      map, is added to the standard force field. Forces proportional to the gradient of
      the density map guide an atomic structure, available from X-ray crystallography,
      into high-density regions of a cryo-EM map. In this paper we describe the
      necessary steps to set up, run, and analyze MDFF simulations and the software
      packages that implement the corresponding functionalities.

PMID- 19398012
TI  - Peptide receptor imaging of prostate cancer with radiolabelled bombesin
      analogues.
AB  - Prostate Cancer (PC) is a type of cancer that is often diagnosed at very early
      stages due to improved detection among man in the Western world. Current imaging
      techniques are not optimal to determine extent of minimal early stage PC even
      though this is of great clinical importance. Human PC and high-grade PIN have
      shown high Gastrin-Releasing Peptide Receptor (GRPR) expression, while normal
      prostate tissue and BPH revealed to be predominantly GRPR-negative. Radiolabelled
      Gastrin-Releasing Peptide (GRP) or bombesin (BN) analogues targeting the GRPR can
      be used as non-invasive tools to diagnose, monitor and potentially treat PC.
      These BN analogues have already proven to be able to image PC in both tumour
      bearing mice and clinical patients showing no important side effects. It's
      desirable that new peptides require fast-track standardised comparative testing
      in relevant PC models to select the best performing BN analogues for further
      evaluation in patients. Although knowledge about GRPR expression and development
      of new BN analogues can be extended, it is time to study performance of BN
      analogues for peptide receptor based imaging in patients validating results of PC
      imaging using histopathology as a golden standard.

PMID- 19398011
TI  - The L1 retrotransposition assay: a retrospective and toolkit.
AB  - LINE1s (L1s) are a class of mammalian non-LTR (long terminal repeat)
      retroelements that make up nearly 20% of the human genome. Because of the
      difficulty of studying the mobilization of endogenous L1s, an exogenous cell
      culture retrotransposition assay has become integral to research in L1 biology.
      This assay has allowed for investigation of the mechanism and consequences of
      mobilization of this retroelement, both in cell lines and in whole animal models.
      In this paper, we outline the genesis of in vitro retrotransposition systems
      which led to the development of the L1 retrotransposition assay in the mid-1990s.
      We then provide a retrospective, describing the many uses and variations of this
      assay, ending with caveats and predictions for future developments. Finally, we
      provide detailed protocols on the application of the retrotransposition assay,
      including lists of constructs available in the L1 research community and cell
      lines in which this assay has been applied.

PMID- 19398013
TI  - Using co-variations in the Hb signal to detect visual activation: a near infrared
      spectroscopic imaging study.
AB  - The premise of this report is that functional Near Infrared Spectroscopy (fNIRS)
      imaging data contain valuable physiological information that can be extracted by
      using analysis techniques that simultaneously consider the components of the
      measured hemodynamic response [i.e., levels of oxygenated, deoxygenated and total
      hemoglobin (oxyHb, deoxyHb and totalHb, respectively)]. We present an algorithm
      for examining the spatiotemporal co-variations among the Hb components, and apply
      it to the data obtained from a demonstrational study that employed a well
      established visual stimulation paradigm: a contrast-reversing checkerboard. Our
      results indicate that the proposed method can identify regions of tissue that
      participate in the hemodynamic response to neuronal activation, but are distinct
      from the areas identified by conventional analyses of the oxyHb, deoxyHb and
      totalHb data. A discussion is provided that compares these findings to other
      recent studies using fNIRS techniques.

PMID- 19398014
TI  - Different roles of the parahippocampal place area (PPA) and retrosplenial cortex
      (RSC) in panoramic scene perception.
AB  - Constructing a rich and continuous visual experience requires computing specific
      details across views as well as integrating similarities across views. In this
      paper, we report functional magnetic resonance imaging (fMRI) evidence that these
      distinct computations may occur in two scene-sensitive regions in the brain, the
      parahippocampal place area (PPA) and retrosplenial cortex (RSC). Participants saw
      different snapshot views from panoramic scenes, which represented clearly
      different views, but appeared to come from the same scene. Using fMRI adaptation,
      we tested whether the PPA and RSC treated these panoramic views as the same or
      different. In the panoramic condition, three different views from a single
      panoramic scene were presented. We did not find any attenuation for panoramic
      repeats in the PPA, showing viewpoint-specificity. In contrast, RSC showed
      significant attenuation for the panoramic condition, showing viewpoint
      integration. However, when the panoramic views were not presented in a continuous
      way, both the specificity in the PPA and the integration in RSC were lost. These
      results demonstrate that the PPA and RSC compute different properties of scenes:
      the PPA focuses on selective discrimination of different views while RSC focuses
      on the integration of scenes under the same visual context. These complementary
      functions of the PPA and RSC enable both specific and integrative representations
      of scenes across several viewpoints.

PMID- 19398015
TI  - Dynamic causal modelling of distributed electromagnetic responses.
AB  - In this note, we describe a variant of dynamic causal modelling for evoked
      responses as measured with electroencephalography or magnetoencephalography (EEG
      and MEG). We depart from equivalent current dipole formulations of DCM, and
      extend it to provide spatiotemporal source estimates that are spatially
      distributed. The spatial model is based upon neural-field equations that model
      neuronal activity on the cortical manifold. We approximate this description of
      electrocortical activity with a set of local standing-waves that are coupled
      though their temporal dynamics. The ensuing distributed DCM models source as a
      mixture of overlapping patches on the cortical mesh. Time-varying activity in
      this mixture, caused by activity in other sources and exogenous inputs, is
      propagated through appropriate lead-field or gain-matrices to generate observed
      sensor data. This spatial model has three key advantages. First, it is more
      appropriate than equivalent current dipole models, when real source activity is
      distributed locally within a cortical area. Second, the spatial degrees of
      freedom of the model can be specified and therefore optimised using model
      selection. Finally, the model is linear in the spatial parameters, which finesses
      model inversion. Here, we describe the distributed spatial model and present a
      comparative evaluation with conventional equivalent current dipole (ECD) models
      of auditory processing, as measured with EEG.

PMID- 19398016
TI  - Multi-contrast large deformation diffeomorphic metric mapping for diffusion
      tensor imaging.
AB  - Diffusion tensor imaging (DTI) can reveal detailed white matter anatomy and has
      the potential to detect abnormalities in specific white matter structures. Such
      detection and quantification are, however, not straightforward. The voxel-based
      analysis after image normalization is one of the most widely used methods for
      quantitative image analyses. To apply this approach to DTI, it is important to
      examine if structures in the white matter are well registered among subjects,
      which would be highly dependent on employed algorithms for normalization. In this
      paper, we evaluate the accuracy of normalization of DTI data using a highly
      elastic transformation algorithm, called large deformation diffeomorphic metric
      mapping. After simulation-based validation of the algorithm, DTI data from normal
      subjects were used to measure the registration accuracy. To examine the impact of
      morphological abnormalities on the accuracy, the algorithm was also tested using
      data from Alzheimer's disease (AD) patients with severe brain atrophy. The
      accuracy level was measured by using manual landmark-based white matter matching
      and surface-based brain and ventricle matching as gold standard. To improve the
      accuracy level, cascading and multi-contrast approaches were developed. The
      accuracy level for the white matter was 1.88+/-0.55 and 2.19+/-0.84 mm for the
      measured locations in the controls and patients, respectively.

PMID- 19398017
TI  - Effects of timing and movement uncertainty implicate the temporo-parietal
      junction in the prediction of forthcoming motor actions.
AB  - The concept of predictive coding supposes the brain to build predictions of
      forthcoming events in order to decrease the computational load, thereby
      facilitating efficient reactions. In contrast, increasing uncertainty, i.e.,
      lower predictability, should increase reaction time and neural activity due to
      reactive processing and believe updating. We used functional magnetic resonance
      imaging (fMRI) to scan subjects reacting to briefly presented arrows pointing to
      either side by pressing a button with the corresponding index finger.
      Predictability of these stimuli was manipulated along the independently varied
      factors "response type" (known hand or random, i.e., unknown order) and "timing"
      (fixed or variable intervals between stimuli). Behavioural data showed a
      significant reaction-time advantage when either factor was predictable,
      confirming the hypothesised reduction in computational load. On the neural level,
      only the right temporo-parietal junction showed enhanced activation upon both
      increased task and timing uncertainty. Moreover, activity in this region also
      positively correlated with reaction time. There was, however, a dissociation
      between both factors in the frontal lobe, as increased timing uncertainty
      recruited right BA 44, whereas increased response uncertainty activated the right
      ventral premotor cortex, the pre-SMA and the DLPFC. In line with the theoretical
      framework of predictive coding as a load-saving mechanism no brain region showed
      significantly increased activity in the lower uncertainty conditions or
      correlated negatively with reaction times. This study hence provided behavioural
      and neuroimaging evidence for predictive motor coding and points to a key role of
      the right temporo-parietal junction in its implementation.

PMID- 19398018
TI  - Quantitative fMRI using hyperoxia calibration: reproducibility during a cognitive
      Stroop task.
AB  - Arterial spin labelling allows simultaneous measurement of both the blood
      oxygenation-level-dependent (BOLD) and the cerebral blood flow (CBF) response to
      changes in neural activity. The addition of a hypercapnia or hyperoxia
      calibration allows additional quantification of changes in the cerebral metabolic
      rate of oxygen (CMRO(2)). In this study we test the reproducibility of
      measurements derived using the hyperoxia approach, during a cognitive Stroop
      task. A QUIPSSII sequence is used at 3 T to collect simultaneous CBF and BOLD
      signal during two 3 min periods of hyperoxia and an 8 min Stroop task. Hyperoxia
      was administered via an open system and end-tidal values were sampled via a nasal
      cannula; average end-tidal values of 60% were reached. This procedure is repeated
      to allow the reproducibility of the estimated parameters to be tested. The use of
      a cognitive Stroop task allows testing of the measurements in frontal and
      parietal regions as well as sensorimotor areas in which previous studies have
      been focussed. We find reduced reproducibility of the calculated parameters
      compared to the hypercapnia approach, thought to be attributable to lower
      absolute BOLD and CBF responses. In particular we do not find 'n' to have
      improved reproducibility compared to other parameters, as has been found in
      previous work using the hypercapnia approach. Across all brain areas we report a
      value of DeltaCMRO(2) of 12% and neurovascular coupling constant n of 2.5.
      Interestingly we find n to be higher in parietal and frontal areas in comparison
      to the primary motor cortex.

PMID- 19398020
TI  - Depression in Parkinson's disease: convergence from voxel-based morphometry and
      functional magnetic resonance imaging in the limbic thalamus.
AB  - Depression is the most frequent psychiatric disorder in Parkinson's disease (PD).
      Although evidence suggests that depression in PD is related to the degenerative
      process that underlies the disease, further studies are necessary to better
      understand the neural basis of depression in this population of patients. In
      order to investigate neuronal alterations underlying the depression in PD, we
      studied thirty-six patients with idiopathic PD. Twenty of these patients had the
      diagnosis of major depression disorder and sixteen did not. The two groups were
      matched for PD motor severity according to Unified Parkinson Disease Rating Scale
      (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using
      an event-related parametric emotional perception paradigm with test retest
      design. Our results showed decreased activation in the left mediodorsal (MD)
      thalamus and in medial prefrontal cortex in PD patients with depression compared
      to those without depression. Based upon these results and the increased neuron
      count in MD thalamus found in previous studies, we conducted a region of interest
      (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume.
      Our results showed an increased volume in mediodorsal thalamic nuclei
      bilaterally. Converging morphological changes and functional emotional processing
      in mediodorsal thalamus highlight the importance of limbic thalamus in PD
      depression. In addition this data supports the link between neurodegenerative
      alterations and mood regulation.

PMID- 19398019
TI  - DTI abnormalities in anterior corpus callosum of rats with spike-wave epilepsy.
AB  - OBJECTIVE: Absence epilepsy is a common seizure disorder in children which can
      produce chronic psychosocial sequelae. Human patients and rat absence models show
      bilateral spike-wave discharges (SWD) in cortical regions. We employed diffusion
      tensor imaging (DTI) in rat absence models to detect abnormalities in white
      matter pathways connecting regions of seizure activity. METHODS: We studied
      Wistar albino Glaxo rats of Rijswijk (WAG/Rij), genetic absence epilepsy rats of
      Strasbourg (GAERS), and corresponding nonepileptic control strains. Ex vivo DTI
      was performed at 9.4 T with diffusion gradients applied in 16 orientations. We
      compared fractional anisotropy (FA), perpendicular (lambda(perpendicular)) and
      parallel (lambda(||)) diffusivity between groups using t-maps and region of
      interest (ROI) measurements. RESULTS: Adult epileptic WAG/Rij rats exhibited a
      localized decrease in FA in the anterior corpus callosum. This area was confirmed
      by tractography to interconnect somatosensory cortex regions most intensely
      involved in seizures. This FA decrease was not present in young WAG/Rij rats
      before onset of SWD. GAERS, which have more severe SWD than WAG/Rij, exhibited
      even more pronounced callosal FA decreases. Reduced FA in the epileptic animals
      originated from an increased lambda(perpendicular) with no significant changes in
      lambda(||). INTERPRETATION: Reduced FA with increased lambda(perpendicular)
      suggests that chronic seizures cause reduction in myelin or decreased axon fiber
      density in white matter pathways connecting regions of seizure activity. These
      DTI abnormalities may improve the understanding of chronic neurological
      difficulties in children suffering with absence epilepsy, and may also serve as a
      noninvasive biomarker for monitoring beneficial effects of treatment.

PMID- 19398021
TI  - Optimization of cortical hierarchies with continuous scales and ranges.
AB  - Although information flow in the neocortex has an apparent hierarchical
      organization, there is much ambiguity with respect to the definition of such a
      hierarchy, particularly in higher cortical regions. This ambiguity has been
      addressed by utilizing observable anatomical criteria, based upon tract tracing
      experiments, to constrain the definition of hierarchy [Felleman D.J. and van
      Essen D.C., 1991. Distributed hierarchical processing in the primate. Cereb.
      Cortex. 1(1), 1-47.]. There are, however, a high number of equally optimal
      hierarchies that fit these constraints [Hilgetag C.C., O'Neill M.A., Young M.P.,
      1996. Indeterminate organization of the visual system. Science. 271(5250), 776
      777.]. Here, we propose a refined constraint set for optimization which utilizes
      continuous, rather than discrete, hierarchical levels, and permits a range of
      acceptable values rather than attempting to fit fixed hierarchical distances.
      Using linear programming to obtain hierarchies across a number of range sizes, we
      find a clear hierarchical pattern for both the original and refined versions of
      the Felleman and Van Essen [Felleman D.J. and van Essen D.C., 1991. Distributed
      hierarchical processing in the primate. Cereb. Cortex. 1(1), 1-47.] visual
      network. We also obtain an optimal hierarchy from a refined set of anatomical
      criteria which allows for the direct specification of hierarchical distance from
      the laminar distribution of labelled cells (Barone P., Batardiere A., Knoblauch
      K., Kennedy H., 2000. Laminar distribution of neurons in extrastriate areas
      projecting to visual areas V1 and V4 correlates with the hierarchical rank and
      indicates the operation of a distance rule. J. Neurosci. 20(9), 3263-3281.), and
      discuss the limitations and further possible refinements of such an approach.

PMID- 19398022
TI  - TIMER: tensor image morphing for elastic registration.
AB  - We propose a novel diffusion tensor imaging (DTI) registration algorithm, called
      Tensor Image Morphing for Elastic Registration (TIMER), which leverages the
      hierarchical guidance of regional distributions and local boundaries, both
      extracted directly from the tensors. Currently available DTI registration methods
      generally extract tensor scalar features from each tensor to construct scalar
      maps. Subsequently, regional integration and other operations such as edge
      detection are performed to extract more features to guide the registration.
      However, there are two major limitations with these approaches. First, the
      computed regional features might not reflect the actual regional tensor
      distributions. Second, by the same token, gradient maps calculated from the
      tensor-derived scalar feature maps might not represent the actual tissue tensor
      boundaries. To overcome these limitations, we propose a new approach which
      extracts regional and edge information directly from a tensor neighborhood.
      Regional tensor distribution information, such as mean and variance, is computed
      in a multiscale fashion directly from the tensors by taking into account the
      voxel neighborhood of different sizes, and hence capturing tensor information at
      different scales, which in turn can be employed to hierarchically guide the
      registration. Such multiscale scheme can help alleviate the problem of local
      minimum and is also more robust to noise since one can better determine the
      statistical properties of each voxel by taking into account the properties of its
      surrounding. Also incorporated in our method is edge information extracted
      directly from the tensors, which is crucial to facilitate registration of tissue
      boundaries. Experiments involving real subjects, simulated subjects, fiber
      tracking, and atrophy detection indicate that TIMER performs better than the
      other methods (Yang et al., 2008; Zhang et al., 2006).

PMID- 19398023
TI  - MEG and EEG data fusion: simultaneous localisation of face-evoked responses.
AB  - We present an empirical Bayesian scheme for distributed multimodal inversion of
      electromagnetic forward models of EEG and MEG signals. We used a generative model
      with common source activity and separate error components for each modality.
      Under this scheme, the weightings of error for each modality, relative to source
      components, are estimated automatically from the data, by optimising the model
      evidence. This obviates the need for arbitrary user-defined weightings. To
      evaluate the scheme, we acquired three types of data simultaneously from twelve
      participants: total magnetic flux (as recorded by 102 magnetometers), orthogonal
      in-plane gradients of the magnetic field (as recorded by 204 planar gradiometers)
      and voltage differences in the electrical field (recorded by 70 electrodes). We
      assessed the relative precision of each sensor-type in terms of signal-to-noise
      ratio (SNR); using empirical sample variances and optimised estimators from the
      generative model. We then compared the localisation of face-evoked responses,
      using each modality separately, with that obtained by their "fusion" under the
      common generative model. Finally, we quantified the conditional precisions of the
      source estimates using their posterior covariance, confirming that EEG can
      improve MEG-based source reconstructions.

PMID- 19398024
TI  - Rapid radiation of Impatiens (Balsaminaceae) during Pliocene and Pleistocene:
      result of a global climate change.
AB  - Impatiens comprises more than 1000 species and is one of the largest genera of
      flowering plants. The genus has a subcosmopolitan distribution, yet most of its
      evolutionary history is unknown. Diversification analyses, divergence time
      estimates and historical biogeography, illustrated that the extant species of
      Impatiens originated in Southwest China and started to diversify in the Early
      Miocene. Until the Early Pliocene, the net diversification rate within the genus
      was fairly slow. Since that time, however, approximately 80% of all Impatiens
      lineages have originated. This period of rapid diversification coincides with the
      global cooling of the Earth's climate and subsequent glacial oscillations.
      Without this accelerated diversification rate, Impatiens would only have
      contained 1/5th of its current number of species, thereby indicating the rapid
      radiation of the genus.

PMID- 19398025
TI  - Interrelationships of chromalveolates within a broadly sampled tree of
      photosynthetic protists.
AB  - The Chromalveolata "supergroup" is a massive assemblage of single-celled and
      multicellular protists such as ciliates and kelps that remains to be
      substantiated in molecular trees. Recent multigene analyses place chromalveolates
      into two major clades, the SAR (Stramenopiles, Alveolata, and Rhizaria) and the
      Cryptophyta+Haptophyta. Here we determined 69 new sequences from different
      chromalveolates to study the interrelationships of its constituent phyla. We
      included in our trees, the novel groups Telonemia and Katablepharidophyta that
      have previously been described as chromalvoleate allies. The best phylogenetic
      resolution resulted from a 6-protein (actin, alpha-tubulin, beta-tubulin,
      cytosolic HSP70, BIP HSP70, HSP90) and a 5-protein (lacking HSP90) alignment that
      validated the SAR and cryptophyte+haptophyte clades with the inclusion of
      telonemids in the former and katablepharids in the latter. We assessed the
      Plastidophila hypothesis that is based on EF2 data and suggest this grouping may
      be explained by horizontal gene transfers involving the EF2 gene rather than
      indicating host relationships.

PMID- 19398026
TI  - Extreme levels of hidden diversity in microscopic animals (Rotifera) revealed by
      DNA taxonomy.
AB  - Knowledge and estimates of species richness at all scales are biased both by our
      understanding of the evolutionary processes shaping diversity and by the methods
      used to delineate the basic units of diversity. DNA taxonomy shows that diversity
      may be underestimated by traditional taxonomy, especially for microscopic
      animals. The effects of such hidden diversity are usually overlooked in
      ecological studies. Here, we estimate hidden diversity in bdelloid rotifers, a
      group of microscopic animals. We analyse cryptic diversity using a coalescent
      approach to infer taxonomical units from phylogenetic trees. Cryptic diversity
      was measured for eight traditional species of bdelloid rotifers and the results
      compared to that of the monogonont rotifer Brachionus plicatilis species complex,
      which is well studied and for which cross-mating experiments have been performed
      to explicitly define some of the species boundaries. A taxonomic inflation of up
      to 34 potential cryptic taxa was found in bdelloids. Cryptic taxa within each
      traditional species may be spatially isolated, but do not have narrower
      ecological niches. The species deemed as generalists exhibit the highest cryptic
      diversity. Cryptic diversity based on molecular characterization is commonly
      found in animals; nevertheless, the amount of cryptic diversity in bdelloids is
      much higher than in other groups analysed so far, maybe because of their peculiar
      parthenogenetic reproduction, other than microscopic size. We discuss this
      hypothesis in the light of the available empirical evidence from other groups of
      microscopic invertebrates, such as tardigrades and mites, which share size,
      habitat heterogeneity, potential for dispersal, and/or parthenogenetic
      reproduction.

PMID- 19398027
TI  - Delta6-desaturase sequence evidence for explosive Pliocene radiations within the
      adaptive radiation of Macaronesian Echium (Boraginaceae).
AB  - The oceanic islands of Macaronesia provide an ideal temporal and spatial context
      to test hypotheses of plant evolution using a novel set of phylogenetic markers,
      Delta(6)-desaturase sequences. In contrast to the limited resolution of standard
      molecular markers (nrDNA and plastid sequences), the Delta(6)-desaturase sequence
      phylogeny of Echium unequivocally reconstructs its active colonization across
      islands and archipelagos (Madeira, the Canary Islands, and Cape Verde), as well
      as its subsequent geographical and ecological speciation. Molecular-clock
      estimates using penalized likelihood and Bayesian inference reveal two radiation
      processes coincident with two dramatic climatic changes recorded in the region:
      the advent of the cold Canarian sea current (ca. 4 Ma) and the establishment of a
      strong seasonality in the Pleistocene (1.8 Ma). Though Echium had available all
      the diversity of present-day Macaronesian environments (xeric and mesic scrub,
      laurisilva, pine forest, and subalpine habitats) in the Miocene, evolutionary
      divergence appears to have been triggered by an extension of fluctuating xeric
      and mesic habitats with the advent of Pliocene conditions. These Echium
      radiations not only fulfill traditional predictions of adaptive radiation (i.e.,
      common ancestry, rapid speciation, and phenotype-environment correlation), but
      also, uniquely among Macaronesian species, trait utility of woodiness. A Pliocene
      transition from annuality to a bush or tree-like condition occurred in early
      Echium lineages. Maintenance of woodiness in major lineages, and reversal to an
      herbaceous condition by three independent events, is reported for the first time
      in plants of oceanic islands.

PMID- 19398028
TI  - Incomplete sampling, outgroups, and phylogenetic inaccuracy: a case study of the
      Greenside Darter complex (Percidae: Etheostomablennioides).

PMID- 19398029
TI  - Physical exercise can reverse the deficit in fear memory induced by maternal
      deprivation.
AB  - Maternal deprivation during the first 10 days of life induces significant
      behavioral alterations in rodents which persist through adulthood. Physical
      exercise reduces the cognitive deficits associated with pharmacologic and
      pathological conditions. Here we investigated whether forced physical exercise
      alters memory deficits caused by postnatal maternal deprivation. Male rats were
      divided into four groups: (1) control, (2) deprived, (3) exercised, and (4)
      deprived+exercised. In groups 2 and 4, pups were deprived from their mothers for
      3h/day during the first 10 days post-birth. In groups 3 and 4, from postnatal day
      45 (PND-45) on, animals were submitted to forced treadmill exercise. At
      adulthood, animals were submitted to four different behavioral tasks: open field,
      Morris water maze (MWM), object recognition (OR) and inhibitory avoidance (IA).
      Maternal deprivation had no effect on open field behavior, but disrupted memory
      in the three other tasks. Physical exercise alone had no effect, except for a
      slight enhancement of MWM learning. Importantly, physical exercise reversed the
      deficit of IA and reduced the deficit of spatial memory but not that of OR seen
      in deprived animals. It is possible that physical exercise may counteract the
      influence of maternal deprivation on neurohumoral or hormonal memory modulatory
      systems related to stress. Indeed, the decreasing order of the effect of exercise
      on the memory disturbances induced by deprivation roughly follows the descending
      degree of stress associated with each task (IA>MWM>OR). Maternal deprivation is
      known to hinder hormonal mechanisms involved in coping with stress.

PMID- 19398030
TI  - Development of strain-specific PCR primers for the identification of
      Fusobacterium nucleatum subsp. fusiforme ATCC 51190(T) and subsp. vincentii ATCC
      49256(T).
AB  - The objective of this study was to develop the strain-specific PCR primers for
      Fusobacterium nucleatum subsp. fusiforme ATCC 51190(T) and F. nucleatum subsp.
      vincentii ATCC 49256(T) based on the nucleotide sequence of the Fs17 and Fv35 DNA
      probes, respectively. The strain specificity was tested against 10 type strains
      of Fusobacterium spp. or subsp., 21 clinical isolates of F. nucleatum from
      Koreans, and five type strains of distinct Fusobacterium species. Primer
      sensitivity was determined by testing serial dilutions (4 ng-4 fg) of the
      purified genomic DNA from each of the type strains. PCR showed that two pairs of
      PCR primers, Fs17-F14/Fs17-R14 and Fv35-F1/Fv35-R1 primers, could produce strain
      specific amplicons from F. nucleatum subsp. fusiforme ATCC 51190(T) and F.
      nucleatum subsp. vincentii ATCC 49256(T), respectively. The two PCR primer sets
      could detect as little as 0.4 pg or 4 pg of the genomic DNA of each target
      strain. These results suggest that the two sets of PCR primers could be used to
      identify F. nucleatum subsp. fusiforme ATCC 51190(T) and F. nucleatum subsp.
      vincentii ATCC 49256(T), particularly for ascertaining the authenticity of the
      strain.

PMID- 19398031
TI  - In the trenches of plant pathogen recognition: Role of NB-LRR proteins.
AB  - As in nearly every discipline of plant biology, new insights are constantly
      changing our understanding of plant immunity. It is now clear that plant immunity
      is controlled by two layers of inducible responses: basal responses triggered by
      conserved microbial features and specific responses triggered by gene-for-gene
      recognition of pathogen effector proteins by host resistance (R) proteins. The
      nucleotide-binding domain leucine-rich repeat (NB-LRR) class of R proteins plays
      a major role in the combat against a wide range of plant pathogens. The variation
      that has been generated and is maintained within these conserved proteins has
      diversified their specificity, subcellular localisations, activation and
      recognition mechanisms, allowing them to specifically adapt to different plant
      pathogen interaction systems. This review addresses recent advances in the
      molecular role of NB-LRR proteins in pathogen recognition and activation of plant
      defence responses.

PMID- 19398032
TI  - Regeneration: Recent advances, major puzzles, and biomedical opportunities.

PMID- 19398033
TI  - Evaluation of candidate reference genes for QPCR during ontogenesis and of immune
      relevant tissues of European seabass (Dicentrarchus labrax).
AB  - The expression level of mRNA can vary significantly in different experimental
      conditions, such as stress, infection, developmental stage or tissue. Suitable
      reference genes are expected to exhibit constant expression levels. However no
      single gene is constitutively expressed in all cell types and under all
      experimental conditions. It has become clear that expression stability of the
      intended reference gene has to be examined before each experiment. For expression
      studies using quantitative real-time PCR (qPCR) at least two reference genes have
      to be applied. So far expression studies in the European seabass (Dicentrarchus
      labrax) as well as in the Gilthead seabream (Sparus aurata) have been performed
      with only one reference gene (S18, Ef-1 alpha or Gapdh). Though significant
      variations showed up in other teleost species such as the Atlantic halibut and
      the zebrafish affirming the need for proper normalization strategies, the present
      study aims at identifying suitable reference genes among nine candidates
      [glyceraldehyde-phosphate-dehydrogenase (Gapdh), beta-actin (two regions of beta
      actin), 40S ribosomal protein S30 (Fau), ribosomal protein L13 a (L13a), beta2
      tubulin (Tubb2) and tyrosine 3 monooxygenase/tryptophan 5-monooxygenase
      activation protein (Tyr)] for expression analysis of 8 developmental stages and a
      tissue panel (spleen, liver, kidney and brain) with samples infected with
      Nodavirus and Vibrio anguillarum in D. labrax. Besides the analysis of raw Ct
      values, the gene expression stability was determined using two different software
      applications BestKeeper and NormFinder. According to both algorithms the best two
      reference genes for an appropriate normalization approach during D. labrax
      development are Ef-1 alpha and L13a whereas in the tissue panel Fau and L13a are
      recommended for qPCR normalization.

PMID- 19398035
TI  - The ion channel activity of the SARS-coronavirus 3a protein is linked to its pro
      apoptotic function.
AB  - The severe acute respiratory syndrome-coronavirus (SARS-CoV) caused an outbreak
      of atypical pneumonia in 2003. The SARS-CoV viral genome encodes several proteins
      which have no homology to proteins in any other coronaviruses, and a number of
      these proteins have been implicated in viral cytopathies. One such protein is 3a,
      which is also known as X1, ORF3 and U274. 3a expression is detected in both SARS
      CoV infected cultured cells and patients. Among the different functions
      identified, 3a is a capable of inducing apoptosis. We previously showed that
      caspase pathways are involved in 3a-induced apoptosis. In this study, we
      attempted to find out protein domains on 3a that are essential for its pro
      apoptotic function. Protein sequence analysis reveals that 3a possesses three
      major protein signatures, the cysteine-rich, Yxx phi and diacidic domains. We
      showed that 3a proteins carrying respective mutations in these protein domains
      exhibit reduced pro-apoptotic activities, indicating the importance of these
      domains on 3a's pro-apoptotic function. It was previously reported that 3a
      possesses potassium ion channel activity. We further demonstrated that the
      blockade of 3a's potassium channel activity abolished caspase-dependent
      apoptosis. This report provides the first evidence that ion channel activity of
      3a is required for its pro-apoptotic function. As ion channel activity has been
      reported to regulate apoptosis in different pathologic conditions, finding ways
      to modulate the ion channel activity may offer a new direction toward the
      inhibition of apoptosis triggered by SARS-CoV.

PMID- 19398036
TI  - Real-time functional imaging for monitoring miR-133 during myogenic
      differentiation.
AB  - MicroRNAs (miRNAs) are a class of non-coding small RNAs that act as negative
      regulators of gene expression through sequence-specific interactions with the 3'
      untranslated regions (UTRs) of target mRNA and play various biological roles. miR
      133 was identified as a muscle-specific miRNA that enhanced the proliferation of
      myoblasts during myogenic differentiation, although its activity in myogenesis
      has not been fully characterized. Here, we developed a novel retroviral vector
      system for monitoring muscle-specific miRNA in living cells by using a green
      fluorescent protein (GFP) that is connected to the target sequence of miR-133 via
      the UTR and a red fluorescent protein for normalization. We demonstrated that the
      functional promotion of miR-133 during myogenesis is visualized by the reduction
      of GFP carrying the miR-133 target sequence, suggesting that miR-133 specifically
      down-regulates its targets during myogenesis in accordance with its expression.
      Our cell-based miRNA functional assay monitoring miR-133 activity should be a
      useful tool in elucidating the role of miRNAs in various biological events.

PMID- 19398034
TI  - Functional roles of bestrophins in ocular epithelia.
AB  - There are four members of the bestrophin family of proteins in the human genome,
      of which two are known to be expressed in the eye. The gene BEST1 (formerly VMD2)
      which encodes the protein bestrophin-1 (Best1) was first identified in 1998.
      Mutations in this gene have now been associated with four clinically
      distinguishable human eye diseases, collectively referred to as
      "bestrophinopathies". Over the last decade, laboratories have sought to
      understand how Best1 mutations could result in eye diseases that range in
      presentation from macular degeneration to nanophthalmos. The majority of our
      knowledge comes from studies that have sought to understand how Best1 mutations
      or dysfunction could induce the classical symptoms of the most common of these
      diseases: Best vitelliform macular dystrophy (BVMD). BVMD is a dominant trait
      that is characterized electrophysiologically by a diminished electrooculogram
      light peak with a normal clinical electroretinogram. This together with the
      localization of Best1 to the retinal pigment epithelium (RPE) basolateral plasma
      membrane and data from heterologous expression studies, have led to the proposal
      that Best1 generates the light peak, and that bestrophins are a family of Ca(2+)
      activated Cl(-) channels (CaCCs). However, data from Best1 knock-out and knock-in
      mice, coupled with the recent discovery of a recessive bestrophinopathy suggest
      that Best1 does not generate the light peak. Recently Best2 was found to be
      expressed in non-pigmented epithelia in the ciliary body. However, aqueous
      dynamics in Best2 knock-out mice do not support a role for Best2 as a Cl(-)
      channel. Thus, the purported CaCC function of the bestrophins and how loss of
      this function relates to clinical disease needs to be reassessed. In this
      article, we examine data obtained from tissue-type and animal models and discuss
      the current state of bestrophin research, what roles Best1 and Best2 may play in
      ocular epithelia and ocular electrophysiology, and how perturbation of these
      functions may result in disease.

PMID- 19398038
TI  - 3-aminobenzanthrone, a human metabolite of the carcinogenic environmental
      pollutant 3-nitrobenzanthrone, induces biotransformation enzymes in rat kidney
      and lung.
AB  - 3-aminobenzanthrone (3-ABA) is the metabolite of the carcinogenic air pollutant 3
      nitrobenzanthrone (3-NBA). 3-ABA was investigated for its ability to induce
      cytochrome P450 1A1 (CYP1A1) and NAD(P)H:quinone oxidoreductase (NQO1) in kidney
      and lung of rats, and for the influence of such induction on DNA adduct formation
      by 3-ABA and 3-NBA. NQO1 is the enzyme that reduces 3-NBA to N-hydroxy-3
      aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize 3-ABA to the same
      intermediate. When activated by cytosolic and and/or microsomal fractions
      isolated from rat lung, the target organ for 3-NBA carcinogenicity, and kidney,
      both compounds generated the same DNA-adduct pattern, consisting of five adducts.
      When pulmonary cytosols isolated from rats that had been treated i.p. with 40
      mg/kg bw of 3-ABA were incubated with 3-NBA, DNA adduct formation was up to 1.7
      fold higher than in incubations with cytosols from control animals. This increase
      corresponded to an increase in protein level and enzymatic activity of NQO1. In
      contrast, no induction of NQO1 expression by 3-ABA treatment was found in the
      kidney. Incubations of 3-ABA with renal and pulmonary microsomes of 3-ABA-treated
      rats led to an increase of up to a 4.5-fold in DNA-adduct formation relative to
      controls. The stimulation of DNA-adduct formation correlated with a higher
      protein expression and activity of CYP1A1 induced by 3-ABA. These results show
      that by inducing lung and kidney CYP1A1 and NQO1, 3-ABA increases its own
      enzymatic activation as well as that of the environmental pollutant, 3-NBA,
      thereby enhancing the genotoxic and carcinogenic potential of both compounds.

PMID- 19398037
TI  - Junctin and triadin each activate skeletal ryanodine receptors but junctin alone
      mediates functional interactions with calsequestrin.
AB  - Normal Ca(2+) signalling in skeletal muscle depends on the membrane associated
      proteins triadin and junctin and their ability to mediate functional interactions
      between the Ca(2+) binding protein calsequestrin and the type 1 ryanodine
      receptor in the lumen of the sarcoplasmic reticulum. This important mechanism
      conserves intracellular Ca(2+) stores, but is poorly understood. Triadin and
      junctin share similar structures and are lumped together in models of
      interactions between skeletal muscle calsequestrin and ryanodine receptors,
      however their individual roles have not been examined at a molecular level. We
      show here that purified skeletal ryanodine receptors are similarly activated by
      purified triadin or purified junctin added to their luminal side, although a lack
      of competition indicated that the proteins act at independent sites.
      Surprisingly, triadin and junctin differed markedly in their ability to transmit
      information between skeletal calsequestrin and ryanodine receptors. Purified
      calsequestrin inhibited junctin/triadin-associated, or junctin-associated,
      ryanodine receptors and the calsequestrin re-associated channel complexes were
      further inhibited when luminal Ca(2+) fell from 1mM to <or=100 microM, as seen
      with native channels (containing endogenous calsequestrin/triadin/junctin). In
      contrast, skeletal calsequestrin had no effect on the triadin/ryanodine receptor
      complex and the channel activity of this complex increased when luminal Ca(2+)
      fell, as seen with purified channels prior to triadin/calsequestrin re
      association. Therefore in this cell free system, junctin alone mediates signals
      between luminal Ca(2+), skeletal calsequestrin and skeletal ryanodine receptors
      and may curtail resting Ca(2+) leak from the sarcoplasmic reticulum. We suggest
      that triadin serves a different function which may dominate during excitation
      contraction coupling.

PMID- 19398040
TI  - Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the
      inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation
      of NF-kappaB pathway in LPS-stimulated murine macrophages.
AB  - Several sesquiterpene lactones that have been isolated from medicinal plants are
      known to have many pharmacological activities. In this study, we investigated the
      anti-inflammatory effects of zedoarondiol, a sesquiterpene lactone isolated from
      the rhizoma of Curcuma heyneana, in lipopolysaccharide (LPS)-stimulated
      macrophage cells. Zedoarondiol dose-dependently inhibited LPS-stimulated nitric
      oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), and interleukin-1beta (IL-1beta) productions in RAW 264.7
      macrophage and in mouse peritoneal macrophage cells. Consistent with these
      findings, in RAW 264.7 cells, zedoarondiol suppressed the LPS-stimulated protein
      levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and
      the mRNA expressions of iNOS, COX-2, TNF-alpha, IL-6, and IL-1beta in a
      concentration-dependent manner. Moreover, molecular data revealed that
      zedoarondiol inhibited LPS-stimulated DNA binding activity and the transcription
      activity of nuclear factor-kappa B (NF-kappaB), and this effect was accompanied
      by decreases in the degradation and phosphorylation of inhibitory kappaB
      (IkappaB)-alpha, and in the subsequent blocking of NF-kappaB translocations to
      the nucleus. Furthermore, zedoarondiol attenuated the phosphorylations of IkappaB
      kinase (IKK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated
      protein kinase (p38), and c-Jun N-terminal kinase (JNK) in LPS-stimulated RAW
      264.7 cells. Taken together, the findings of the present study indicate that
      zedoarondiol inhibits iNOS, COX-2, and pro-inflammatory cytokine expressions by
      suppressing the phosphorylations of IKK and MAPKs, and by subsequently
      inactivating the NF-kappaB pathway. These relations reveal, in part, the
      mechanism underlying the anti-inflammatory properties of zedoarondiol.

PMID- 19398039
TI  - Genetic structure of Plasmodium falciparum populations between lowland and
      highland sites and antimalarial drug resistance in Western Kenya.
AB  - Human travel to malaria endemic lowlands from epidemic highlands has been shown
      to increase the risk of malaria infections in the highlands. In order to gain
      insight on the impact of human travel, we examined prevalence, genetic
      variability and population genetic structure of Plasmodium falciparum in
      asymptomatic children from one highland site and three surrounding malaria
      endemic lowland sites in Western Kenya, using multilocus microsatellite
      genotyping. We further analyzed the frequencies of mutations at the genes
      conferring resistance to chloroquine and sulfadoxine-pyrimethamine. We found a
      significant decrease in malaria prevalence in the highland site from 2006 to
      2007, 1 year after the introduction of the artemisinin-based combination therapy
      as first-line treatment for uncomplicated malaria and the scale-up of insecticide
      treated bed nets. Population genetic diversity, measured by the number of
      observed and effective microsatellite alleles and Nei's unbiased genetic
      diversity, was high and comparable for both highland and lowland populations.
      Analysis of molecular variance did not detect a significant genetic structure
      across highland and lowland regions. Similarly, mutations at key antimalarial
      resistance codons of the pfcrt, pfmdr1, pfdhfr and pfdhps genes were found at
      comparable high frequencies in all four sites. High level of gene flow and lack
      of significant genetic structure in malaria parasites between highland and
      lowland areas suggest the importance of human travel in shaping parasite
      population structure.

PMID- 19398041
TI  - Mitochondria: one of the origins for autophagosomal membranes?
AB  - Macroautophagy is a transport pathway to the lysosome/vacuole that contributes to
      the degradation of numerous intracellular components. Despite the recent advances
      achieved in the understanding of the molecular mechanism underlying
      macroautophagy, the membrane origin of autophagosomes, the hallmark of this
      process is still a mystery. It has been suggested that mitochondria may be one of
      the lipid sources for autophagosome formation and that possibly this organelle
      provides the phosphatidylethanolamine (PE) that covalently links to the members
      of the ubiquitin-like Atg8/microtubule-associated protein 1 light chain 3 (LC3)
      protein family. These lipidated proteins are inserted into the outer and inner
      surface of autophagosomes and are essential for the biogenesis of these large
      double-membrane vesicles. However, because PE is an integral component of all
      cellular membranes, designing appropriate experiments to determine the origin of
      the autophagosomal PE is not easy. In this review, we discuss the idea that
      mitochondria provide the pool of PE necessary for the autophagosome biogenesis
      and we propose some possible experimental approaches aimed to explore this
      possibility.

PMID- 19398042
TI  - Is research ethics committee approval necessary for publication of prospective
      surgical research studies?

PMID- 19398043
TI  - Prediction of proximal femur strength using a CT-based nonlinear finite element
      method: differences in predicted fracture load and site with changing load and
      boundary conditions.
AB  - The annual occurrence of hip fracture due to osteoporosis as of 2002 had reached
      120,000 in Japan. The increase has been very rapid. From a biomechanical
      perspective, hip fractures are thought to be caused in real settings by different
      directions of loading. Thus, clarification of the loading directions under which
      the proximal femur is most vulnerable to fracture would be helpful for
      elucidating fracture mechanics and establishing preventive interventions. The
      purpose of the current study was to clarify the influence of loading direction on
      strength and fracture site of the proximal femur using the CT-based nonlinear FE
      method to determine loading directions under which the proximal femur is most
      vulnerable to fracture. Contralateral femora were analyzed in 42 women with hip
      fracture (mean age, 82.4 years), comprising 20 neck fractures and 22 trochanteric
      fractures. Within 1 week after fracture, quantitative CT of the contralateral
      femur was performed in each patient and 3-dimensional FE models were created. One
      stance loading configuration (SC) and four different fall loading configurations
      (FC) were assigned. Nonlinear FE analysis was performed. Differences in fracture
      loads depending on differences in loading direction were analyzed and
      correlations among fracture loads in different loading directions were assessed.
      Next, fracture sites were also analyzed. Mean predicted fracture load in the SC
      was 3150 N. Mean fracture loads were 2270 N in FC1, 1060 N in FC2, 980 N in FC3,
      and 710 N in FC4. The correlation between predicted fracture loads in SC and
      those in each FC was significant with a correlation coefficient of 0.467-0.631.
      Predicted fracture sites in the SC appeared at the subcapital region in all
      patients and were categorized as neck fracture. However, trochanteric fractures
      occurred in all fall configurations except FC1. In FC1, a significant correlation
      was seen between real fracture type and predicted type. The current investigation
      could contribute to the acquisition of useful knowledge allowing the
      establishment of more efficacious means of preventing hip fractures.

PMID- 19398044
TI  - Differences in early osteogenesis and bone micro-architecture in anterior lumbar
      interbody fusion with rhBMP-2, equine bone protein extract, and autograft.
AB  - PURPOSE: To investigate the microstructural differences and responsible
      mechanisms in early bone formation in anterior lumbar interbody fusion (ALIF) in
      the spine using rhBMP-2 (INFUSE), equine bone protein extract (COLLOSS E) or
      autograft. METHODS: Twelve Danish female landrace pigs underwent a 3-level ALIF
      procedure at L3-6. PEEK interbody cages packed with rhBMP-2, COLLOSS E, or
      autograft were inserted. The animals were divided into two groups of six, and
      observed for four and eight weeks postoperatively. MicroCT was performed for
      evaluation of microstructure of the bone within the cage. A mathematical finite
      element model was developed to investigate the aqueous behavior within the cages
      when exposed to external compressive forces. RESULTS: At 4 weeks postoperative
      bone surface volume fraction (BS/TV) using rhBMP-2 was higher than with use of
      COLLOSS E and autograft, while trabecular thickness (Tb.Th.) was lower using
      rhBMP-2 at this time-point. At eight weeks BS/TV and trabecular number (Tb.N.)
      were still higher using rhBMP-2 than autograft and COLLOSS E. Connectivity
      density was significantly higher using rhBMP-2 than using autograft or COLLOSS E
      at both time-points. Between four- and eight-week time-points BV/TV and Tb.Th.
      rose while Tb.N. declined using rhBMP-2. The degree of anisotropy and the
      calculated amount of trabeculae with main direction along the spinal axis, were
      higher at four weeks using COLLOSS E. rhBMP-2 had the highest amount of
      trabeculae directed along the spinal axis at eight weeks. A change in main
      direction between four and eight weeks was observed for both autograft and rhBMP
      2. The numerical results from the finite element model verify that significantly
      different flow pattern emerges as the boundary conditions are altered. At four
      weeks there was an evident correlation between trabecular orientation and flow
      pattern using rhBMP-2. CONCLUSION: This study reveals large differences in
      microstructure in the early osteogenesis and explains important mechanisms of
      early bone formation using rhBMP-2, COLLOSS E or autograft treatment. These
      differences might explain some of the unfortunate events reported such as edema,
      swelling, and excessive bone formation using different bone graft substitutes in
      spinal fusion procedures.

PMID- 19398046
TI  - Osteocyte morphology in human tibiae of different bone pathologies with different
      bone mineral density--is there a role for mechanosensing?
AB  - Matrix strains due to external loading are different in bones of different
      pathologies with different bone mineral density (BMD), and are likely sensed by
      the osteocytes, the putative bone mechanosensors. The mechanosensitivity of
      osteocytes appears to be strongly influenced by their morphology. In this study,
      we explored the possibility that osteocyte morphology might play a role in
      various bone pathologies with different BMD. Confocal laser scanning microscopy
      and nano-CT were used to quantitatively determine 3D morphology and alignment of
      osteocytes and osteocyte lacunae in human proximal tibial bone with relatively
      low (osteopenic), medium (osteoarthritic), and high (osteopetrotic) BMD.
      Osteopenic osteocytes were relatively large and round (lengths 8.9:15.6:13.4
      microm), osteopetrotic osteocytes were small and discoid shaped (lengths
      5.5:11.1:10.8 microm), and osteoarthritic osteocytes were large and elongated
      (lengths 8.4:17.3:12.2 microm). Osteopenic osteocyte lacunae showed 3.5 fold
      larger volume and 2.2 fold larger surface area than osteoarthritic lacunae,
      whereas osteopetrotic lacunae were 1.9 fold larger and showed 1.5 fold larger
      surface area than osteoarthritic lacunae. Osteopetrotic osteocyte lacunae had
      lower alignment than osteopenic and osteoarthritic lacunae as indicated by their
      lower degree of anisotropy. The differences in 3D morphology of osteocytes and
      their lacunae in long bones of different pathologies with different BMD might
      reflect an adaptation to matrix strain due to different external loading
      conditions. Moreover, since direct mechanosensing of matrix strain likely occurs
      by the cell bodies, the differences in osteocyte morphology and their lacunae
      might indicate differences in osteocyte mechanosensitivity. The exact
      relationship between osteocyte morphology and bone architecture, however, is
      complex and deserves further study.

PMID- 19398045
TI  - BMP2 is essential for post natal osteogenesis but not for recruitment of
      osteogenic stem cells.
AB  - The effects of BMP2 on bone marrow stromal cell differentiation and bone
      formation after bone marrow ablation were determined using C57 BL/6J (B6) mice.
      Inhibition of BMP2 expression with lentiviral BMP2 shRNA prevented both
      mineralized nodule formation in vitro and bone formation in vivo, and blocked the
      expression of Runx2 and osterix, transcriptional determinants of terminal
      osteogenic differentiation. No effect was observed on the expression of Sox9, a
      transcription factor, which is the one of the first transcriptional determinant
      to be expressed in committed chondroprogenitor and osteoprogenitor cells. In
      vitro studies showed that exogenously added BMP7 rescued the expression of
      osterix and enhanced the expression of Sox9, but had no effect on the expression
      of Runx2, while it only partially recovered the development of mineral deposition
      in the cultures. On the other hand, the exogenous addition of BMP2 rescued both
      Runx2 and osterix expression, did not enhance the expression of Sox9, but fully
      recovered the inhibition of mineral deposition in the cultures. Using antibodies
      against CD146 and Sox9, immunohistological examination of the cell populations
      found in the medullary space three days after bone marrow ablation, showed
      qualitatively equal numbers of cells expressing these skeletal progenitor and
      stem cell markers in control and BMP2 shRNA treated animals. Fluorescence
      Activated Cell Sorting (FACS) analysis of the cells found with the marrow
      cavities at three days after marrow ablation using CD146 antibody showed near
      equal numbers of immunopositive cells in both control and shRNA treated animals.
      In summary, the differences observed in vitro for BMP2 and BMP7 on osteogenic
      gene expression and mineralization suggest that they have differing effects on
      bone cell differentiation. These results further demonstrate that in vivo BMP2 is
      a central morphogenetic regulator of post natal osteoprogenitor differentiation,
      but does not affect recruitment of progenitors to the osteoblastic lineage.

PMID- 19398047
TI  - Incentive motivation, conditioning, stress, and neuropsychiatric disorders: a
      tribute to Jane Stewart.

PMID- 19398048
TI  - The International Society of Electrocardiology.

PMID- 19398049
TI  - Interview with Peter W. Macfarlane by Ljuba Bacharova.

PMID- 19398050
TI  - Diagnosis of acute right ventricular infarction.

PMID- 19398051
TI  - Electrocardiographic diagnosis of left ventricular hypertrophy: depolarization
      changes.
AB  - Electrocardiographic signs of left ventricular hypertrophy (LVH) are on one hand
      accepted as independent cardiovascular risk factors and indicators of target
      organ damage in hypertensive patients, but, on the other hand they are strongly
      criticized for their low sensitivity. In this paper, a historic perspective on
      the ECG diagnosis of LVH is presented, showing the development of current views
      on the role of ECG in LVH detection. Based on the fact that ECG provides
      information on the electrical properties of myocardium and on new knowledge about
      electrical remodeling in LVH, a shift of paradigm in our consideration of the
      diagnosis of left ventricular hypertrophy is proposed, based on changes in the
      electrical properties of hypertrophied myocardium. This new paradigm could
      explain the broad spectrum of QRS patterns seen in LVH, including increased QRS
      voltage, prolonged duration of QRS complex, left axis deviation, prolonged
      intrinsicoid deflection, LBBB and LAFB patterns, as well as pseudo-normal ECG
      findings.

PMID- 19398052
TI  - Atrial fibrillation detected by dual-chamber pacemakers and structural heart
      disease.

PMID- 19398053
TI  - Selenium and thyroid hormone axis in critical ill states: an overview of
      conflicting view points.
AB  - In critical ill states the plasma selenium levels are low and inversely
      correlated with the severity and outcome of the disease. The plasma selenium
      levels indicate the amount of circulating selenoproteins and selenoenzymes. These
      are important for the maintenance of the redox system, modulating the immune
      system and also for thyroid hormone metabolism. Not only all three deiodinases
      (D1-3) are selenoenzymes, but within the thyroid gland there are several other
      selenoenzymes, which are important for the maintenance of normal thyroid
      function. In critical ill states also triodothyronine (T3) is low and reverse T3
      elevated, and also TSH and thyroxin (T4) are low, correlating like low plasma
      selenium with the severity of the disease. Subsequently, several intervention
      trials had been performed to evaluate whether an adjuvant selenium
      supplementation might attenuate the course of the disease and improve outcome.
      The selenium supplementation improved outcome and even reduced mortality in some
      but not all prospective randomized trials. A few prospective randomized
      intervention trials with selenium supplementation had also been performed to
      evaluate the hypothesis, whether low selenium is the cause of low-T3-syndrome,
      however, with conflicting results and no clear evidence that low D1 activity is
      due to the selenium deficiency in critical illness. Because D1 catalyses the
      conversion of T4 to T3 and also the clearance of reverse T3, low D1 activity
      would sufficiently explain low plasma T3 and elevated reverse T3. It had been,
      however, clearly shown that cytokines are responsible for the inhibition of D1
      activity, but D2 and D3 are even higher during acute inflammation in critically
      ill patients. One of the most important effects of selenium on the immune system
      seems to be the reduction of cytokine release and therefore an indirect
      connection between low selenium and low D1 activity has to be postulated and not
      a lower D1 activity due to lower availability of selenium for the D1 expression.

PMID- 19398054
TI  - Influence of exogenous iron, calcium, protein and common salt on the
      bioaccessibility of zinc from cereals and legumes.
AB  - We have earlier reported the zinc bioaccessibility from cereals and pulses and
      documented the influence of heat processing, germination and fermentation on the
      same. In the present study, we have assessed the influence of exogenous iron and
      calcium equivalent to their supplemental levels on the bioaccessibility of zinc
      from food grains that generally are the major components of meal in India.
      Bioaccessibility measurement was made by a procedure involving equilibrium
      dialysis during simulated gastrointestinal digestion. Exogenous iron equivalent
      to therapeutic levels (5mg per 10g of cereal-legume combination) significantly
      reduced the bioaccessibility of zinc from the food grains tested, the percent
      reduction being 32.4. Exogenous calcium equivalent to therapeutic levels (83mg
      per 10g of the cereal-legume combination) also significantly reduced (by 27.4%)
      the bioaccessibility of zinc from the tested food grains. The negative influence
      of exogenous iron and calcium was similar in both raw and cooked grains. Such
      negative influences on the bioaccessibility of zinc were however not seen when
      exogenous iron and calcium were only moderate (up to four times the intrinsic
      level). A study of the influence of exogenous protein on the bioaccessibility of
      zinc from food grains revealed that soy protein isolate added at amounts to
      result in a total protein content of 20% produced contrasting effects on zinc and
      iron bioaccessibility from cereals - rice and sorghum. While soy protein had a
      negative effect on iron bioaccessibility from these food grains, the same
      produced an enhancing effect on zinc bioaccessibility (an increase of 50% and 90%
      increase) from raw and cooked grain, respectively). Exogenous sodium chloride (at
      5% level) potentiated the positive effect of soy protein on zinc
      bioaccessibility, and effectively countered its negative effect on iron
      bioaccessibility. The observed negative influence of supplemental iron and
      calcium on zinc bioaccessibility suggests that zinc supplementation may be
      necessary in the Indian context, whenever iron and calcium supplements are taken,
      to compensate for the reduction in zinc bioaccessibility.

PMID- 19398055
TI  - Iodine concentration of milk in a dose-response study with dairy cows and
      implications for consumer iodine intake.
AB  - Most feed is poor in iodine and iodine supplementation of cow's diets must
      guarantee milk iodine concentrations for humans that contribute to prevention of
      the deficiency and minimize the risk of exceeding an upper limit of iodine
      intake. Five Holstein cows were fed four iodine doses (via Ca(Iota
      O(3))(2).6H(2)O). In four sequential 14-d periods, doses of 0.2 (basal diet),
      1.3, 5.1, and 10.1 mg iodine kg(-1) diet dry matter (DM) were administered.
      Samples of milk were collected during each period; blood was also sampled from
      each cow for each iodine dosage. In an 18-d depletion period, a non-supplemented
      diet was provided. Iodine was determined by inductively coupled plasma-mass
      spectrometry. The iodine content of milk and serum reflected the iodine dosages
      in feed significantly. The levels for the four doses tested in milk were 101+/
      32, 343+/-109, 1215+/-222, and 2762+/-852 microg iodine kg(-1). The total amount
      of iodine in milk per day was 30-40% of ingested supplemental iodine. Omitting
      additional iodine resulted in a short-term reduction of serum and milk iodine
      following an exponential decay function. The iodine supplementation of 0.5-1.5 mg
      kg(-1) diet DM represents the requirement of the cow, resulting in 100-300 microg
      iodine L(-1) milk, which optimally contributes to human supply. The maximum
      dietary levels of former and present EU legislations (10 and 5 mg iodine kg(-1)
      cow feed) increase the risk of iodine excess in humans.

PMID- 19398056
TI  - Mn and Cu concentrations in mixed saliva of elementary school children in
      relation to sex, age, and dental caries.
AB  - To examine the standard Mn and Cu concentrations in mixed saliva from children
      and the relationship between these levels and dental caries, resting mixed saliva
      samples obtained from 527 children of an elementary school in Kitakyushu City
      were collected at 10:00-11:30 a.m. during December 2004. The Mn and Cu
      concentrations were determined using simultaneous multi-element atomic absorption
      spectrometry. The standard Mn and Cu levels were 22.0+/-15.2 and 3.8+/-4.1ng/mL,
      respectively, in the sound teeth group. Mn levels were significantly higher in
      boys (25.4+/-17.4ng/mL) than girls (19.1+/-12.3ng/mL) and also higher in upper
      (25.5+/-16.4ng/mL) than lower (19.0+/-13.5ng/mL) grades. The Cu level was
      unaffected by sex and age in the sound teeth group. The Cu level in children with
      caries experience (5.7+/-5.3ng/mL) was significantly higher than that of the
      sound teeth group. Moreover, the Cu levels in children with untreated caries were
      significantly higher than that of the sound teeth group, and increased with the
      number of untreated teeth. No significant difference was found in the Cu
      concentrations between the group in which all decayed teeth were treated and the
      sound teeth group. The Mn levels were similar with or without caries and
      treatment. These findings indicate that the Mn level in mixed saliva depended on
      sex and age, and suggest the possibility of Cu dissolving into mixed saliva by
      demineralization due to dental caries.

PMID- 19398057
TI  - Thoracic aortic aneurysm patients with Chlamydophila pneumoniae infection showed
      a shift in trace element levels in serum and diseased aortic tissue.
AB  - Few studies have been performed on trace elements in tissues and serum in
      cardiovascular disease and none in aortic aneurysm. In this study the
      concentrations of 10 trace elements were determined in serum and aneurysmatic
      aortic tissue from 23 patients undergoing thoracic surgery. Macroscopically,
      normal thoracic aortic tissue specimens from 10 forensic autopsies and serum from
      23 healthy blood donors served as controls. DNA from the intracellular
      respiratory pathogen Chlamydophila pneumoniae (C. pneumoniae), which may be
      involved in the pathogenesis of atherosclerosis, was found in 26% (6/23) of the
      patients but in none of the controls. The serum copper/zinc ratio, a well-known
      marker of ongoing infection and/or inflammation, was higher (26%, p<0.001) in
      aneurysm patients. C. pneumoniae requires iron for its growth. In our aneurysm
      patients iron was higher in serum (by 54%, p<0.001) and aneurysmal tissue (by
      60%, p<0.001). Although calcium was lower in patient sera (by 8%, p<0.001), it
      tended to be higher (by 20%, ns) in aneurysmatic tissue. In addition, mercury
      concentrations in serum and aneurysmatic tissue were positively correlated
      (r=0.51, p<0.05). Moreover, C. pneumoniae-positive aneurysmatic tissues had lower
      concentrations of manganese (46%, p<0.05) and zinc (26%, ns) but a higher
      concentration of mercury (50%, p<0.05) than C. pneumoniae-negative aneurysmatic
      tissues. In conclusion, aneurysm patients showed a shift in trace element levels
      in serum and in the diseased part of the aorta, the pattern being partly
      different in C. pneumoniae-positive compared with C. pneumoniae-negative
      patients. The results are compatible with active infection and/or inflammation,
      possibly initiated by C. pneumoniae.

PMID- 19398058
TI  - The time-trend and the relation between smoking and circulating selenium
      concentrations in Norway.
AB  - OBJECTIVES: The objectives of this study were to investigate biomarkers of
      selenium status in relation to smoking habits and to analyze the time-trend of
      selenium in serum (S-Se) in Norway during the time period 1995-2006. METHODS: The
      impact of smoking habits was investigated in a population recruited to a cross
      sectional study of blue-collar workers in the southern part of the country
      (n=98). The time-trend was studied in all subjects who delivered blood samples
      for the determination of S-Se to a large commercial clinical chemistry laboratory
      in Norway. RESULTS: Smokers had 0.14 and 0.20 micromol/L lower concentrations of
      selenium in whole blood (B-Se) and serum, respectively, than non-smokers. The
      amount of smoking, as assessed by the serum cotinine concentration, was
      negatively associated with the B-Se concentration (Pearson's r=-0.43). The 1/3 of
      the blue-collar workers with the lowest concentrations of B-Se or S-Se had lower
      activity of glutathione peroxidase in serum (S-GSHpx) than the remaining
      subjects. Snuff users had about the same levels of B-Se and S-Se as the non
      smokers, although they had about the same amount of nicotine metabolites in urine
      and serum as the smokers. A decreasing trend of S-Se was observed during the
      observation period from 1995 to 2006. The mean concentration was 1.26 micromol/L
      in 1995, while the lowest mean concentration was measured in 2003 (1.01
      micromol/L). CONCLUSION: Smoking, but not snuffing, is associated with lower
      concentrations of B-Se and S-Se. The reduction of B-Se is negatively associated
      with the nicotine biomarker cotinine in serum. A substantial proportion of blue
      collar workers had not maximized the activity of S-GSHpx. Selenium status may
      have become poorer since 1995.

PMID- 19398059
TI  - Epidemiology of trace elements deficiencies in Belgian beef and dairy cattle
      herds.
AB  - Selenium (Se), iodine (I), zinc (Zn) and copper (Cu) deficiencies in cattle have
      been reported in Europe. These deficiencies are often associated with diseases.
      The aim of the study was to assess trace element status in Belgian cattle herds
      showing pathologies and to compare them to healthy cattle herds. Eighty-two beef
      herds with pathologies, 11 healthy beef herds, 65 dairy herds with pathologies
      and 20 healthy dairy herds were studied during barn period. Blood and/or milk
      samples were taken in healthy animals. Plasma Zn, Cu, inorganic I (PII) and
      activity of glutathione peroxidase in erythrocytes (GPX) were assayed. In milk, I
      concentration was measured. Data about pathologies and nutrition in the herds
      were collected. According to defined thresholds, it appeared that a large
      proportion of deficient herds belonged to "sick" group of herds. This conclusion
      was supported by the mean value of trace elements and by the fact that a majority
      of individual values of trace elements was below the threshold. Dairy herds had
      mean values of trace elements higher than beef herds. More concentrates and
      minerals were used in healthy herds versus "sick" herds. These feed supplements
      were also used more often in dairy herds, compared to beef herds. Trace elements
      deficiencies are present in cattle herds in Belgium and are linked to diseases.
      Nutrition plays a major role in the trace elements status.

PMID- 19398060
TI  - Differential quantitative zinc-induced expression of human metallothionein
      isogenes in haematopoietic precursor cell lines.
AB  - The expression pattern of functional members of the metallothionein (MT) gene
      family was studied in the haematopoietic precursor cell lines, K562, DAMI, MEG
      01, and ELF-153 in order to strengthen the proposed function of MT in
      differentiation. Cells were cultured in RPMI 1640 with 10% (v/v) foetal calf
      serum, with or without different zinc supplements. Expression of MT isogenes was
      analysed by quantitative real-time PCR (RT-PCR) using mRNA extracted from
      cultured cells. The more mature K562, DAMI, and MEG-01 cell lines exhibited
      transcription of all MT isogenes, except MT-3 and MT-4. Relative quantitative
      expression of MT isogenes in the mature cell lines such as K562, DAMI, and MEG-01
      was higher than in the immature ELF-153 cell line. Immunohistochemical staining
      (IHC) reveals an increased MT protein biosynthesis in more mature cell lines such
      as K562, DAMI and MEG-01 greater than in the immature ELF-153 cell line. Real
      time PCR and immunohistochemical staining for investigating the effect of phorbol
      ester and hemin (haematopoietic differentiation stimuli) on expression of MT
      isogenes in K562 cells reveals that phorbol ester induces increased MT
      transcription and biosynthesis. Therefore, to our knowledge, the role of MT in
      differentiation in human haematopoietic precursor cell lines is here reported for
      the first time.

PMID- 19398061
TI  - Dietary selenium requirements based on tissue selenium concentration and
      glutathione peroxidase activities in old female rats.
AB  - Dietary nutrient requirements for older animals have been studied far less than
      have requirements for young growing animals. To determine dietary selenium (Se)
      requirements in old rats, we fed female weanling rats a Se-deficient diet (0.007
      microg Se/g) or supplemented rats with graded levels of dietary Se (0-0.3 microg
      Se/g) as Na(2)SeO(3) for 52 weeks. At no point did Se deficiency or level of Se
      supplementation have a significant effect (P>0.05) on growth. To determine Se
      requirements, Se response curves were determined for 7 Se-dependent parameters.
      We found that minimum dietary Se requirements in year-old female rats were at or
      below 0.05 microg Se/g diet based on liver Se, red blood cell glutathione
      peroxidase (Gpx1) activity, plasma Gpx3 activity, liver and kidney Gpx1 activity,
      and liver and kidney Gpx4 activity. In conclusion, this study found that dietary
      Se requirements in old female rats were decreased at least 50% relative to
      requirements found in young, rapidly growing female rats. Collectively, this
      indicates that the homeostatic mechanisms related to retention and maintenance of
      Se status are still fully functional in old female rats.

PMID- 19398062
TI  - Acute high-dose sodium selenite administration improves intestinal
      microcirculation without affecting cytokine release in experimental endotoxemia.
AB  - We evaluated the effects of acute high-dose sodium selenite (SEL) administration
      on the intestinal microcirculation and the release of the cytokines TNF-alpha, IL
      1beta, IL-6 and IL-10 in experimental endotoxemia (induced by lipopolysaccharide
      LPS). Three groups of animals (n=30) were studied: control group, endotoxemic
      group (15 mg kg(-1) i.v. LPS from E. coli) and SEL-treated LPS group (100 microg
      kg(-1) SEL i.v.). SEL treatment resulted in a significant reduced number of
      firmly adhering leukocytes in intestinal submucosal venules and reduced
      significantly the impairment of the intestinal functional capillary density.
      Despite of the improvement of microcirculatory parameters, we did not detect any
      changes in the pattern of cytokine release. In conclusion, administration of high
      dose sodium SEL attenuates leukocyte adhesion and improves capillary perfusion
      within the intestinal microcirculation without affecting release of the cytokines
      TNF-alpha, IL-1beta, IL-6 and IL-10 in experimental endotoxemia.

PMID- 19398063
TI  - Antioxidants activities and concentration of selenium, zinc and copper in preterm
      and IUGR human placentas.
AB  - The aim of this study was to examine changes in activities of cytochrome c
      oxidase (CCO), glucose-6-phosphate dehydrogenase (G6PDH), Cu-Zn superoxide
      dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), glutathione (GSH) levels
      and copper (Cu), zinc (Zn) and selenium (Se) concentrations, and to assess the
      possible differences between preterm placentas, placentas from term pregnancies
      complicated by intrauterine growth restriction (IUGR) and full-term control
      placentas. The enzyme activities and the level of GSH decreased in IUGR and
      preterm placentas in comparison with the control group. CCO activity and GSH
      level in preterm placentas were markedly lower compared with the IUGR (P<0.01;
      P<0.05) and control (P<0.01; P<0.05) placentas, respectively. In IUGR placentas
      the level of Cu was reduced by 23% (P<0.05) and Zn by 37%. In preterm placentas
      the level of Cu was reduced by 19% and Zn by 42%. Se level in IUGR and preterm
      placentas was higher (P<0.05) by 28% and 32% than in control group, respectively.
      The strong relation was observed between birth weight and CCO activity, birth
      weight and Cu-Zn SOD activity, and a low level of Zn and Cu influenced the birth
      weight especially in IUGR cases. Moreover, the strong inverse correlation between
      Se level and birth weight, Se level and placental weight and Se level and CCO
      activity are new findings.

PMID- 19398064
TI  - Time for a reassessment of the use of Kava in anxiety?

PMID- 19398065
TI  - Therapeutic effects of Chiljehyangbuhwan on primary dysmenorrhea: a randomized,
      double blind, placebo-controlled study.
AB  - OBJECTIVE: This clinical study was conducted to investigate the efficacy and
      safety of an oriental herbal medicine native to Korea, Chiljehyangbuhwan, in
      treating primary dysmenorrhea. DESIGN AND SETTING: A total of 100 primary
      dysmenorrhea patients who visited Kyung Hee University Korean Oriental Medicine
      Hospital between July 19 2004 and August 27 2004 were recruited. Secondary or
      drug-related dysmenorrhea was screened out through interviews and examination.
      The patients were grouped by fixed blocked randomization and administered either
      Chiljehyangbuhwan or placebo for one menstrual period in a double blind model.
      Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), and Multidimensional
      Verbal Rating Scale (MVRS) were used to evaluate dysmenorrhea severity. A total
      of 71 patients who passed the screening test and remained to the last were
      divided into either placebo or Chiljehyangbuhwan group, and each were further
      split into smaller subsets (indication, non-indication, and unspecified group)
      according to Korean Oriental medical diagnosis. RESULTS: In the non-indication
      group, the placebo and Chiljehyangbuhwan group did not show significant
      difference in VAS, VRS, and MVRS scores before medication (1st VAS, 1st VRS, 1st
      MVRS), after medication (2nd VAS, 2nd VRS, 2nd MVRS), and in changes in scores
      before and after (DeltaVAS, DeltaVRS, DeltaMVRS). In the indication group, the
      placebo and Chiljehyangbuhwan group showed significant difference in change in
      VAS and MVRS scores (DeltaVAS and DeltaMVRS). No evidence of toxicity could be
      found, and no serious adverse reactions to Chiljehyangbuhwan were reported.
      CONCLUSION: The results suggest that Chiljehyangbuhwan is effective and safe in
      treating primary dysmenorrhea when prescribed appropriately under Korean Oriental
      medical diagnosis.

PMID- 19398066
TI  - Different frequencies of acupuncture treatment for chronic low back pain: an
      assessor-blinded pilot randomised controlled trial.
AB  - OBJECTIVES: To examine the feasibility of a main RCT to compare the effectiveness
      of two frequencies (2 versus 5 times/week) of acupuncture treatment for chronic
      low back pain (LBP). METHODS: Participants (n=30) with chronic LBP were
      randomised into two groups to receive 10 acupuncture treatments: Low Frequency
      Group, 2 times/week for five weeks (n=15); High Frequency Group, 5 times/week for
      two weeks (n=15). The following outcomes were measured blindly at baseline, 2
      weeks, 5 weeks, 3 months and 1 year: pain on a VAS, functional disability using
      the RMDQ, quality of life using the Measure Yourself Medical Outcome Profile
      (MYMOP-2), psychological impact with the Coping Strategies Questionnaire (CSQ)
      and Pain Locus of Control (PLC) questionnaire. Two objective outcomes, the
      Shuttle Walk Test (SWT) and Lateral Trunk Flexibility (LTF), were also measured.
      RESULTS: The compliance rate was 100% for each group. Some of the measurements
      were shown to be sensitive (VAS, RMDQ, MYMOP-2 Wellbeing). 66-330 participants
      would be required for a fully powered non-inferiority trial. The groups were
      balanced at baseline for LBP and demographic characteristics. There were no
      significant differences between the groups in terms of any of the outcomes, at
      each follow-up time point. It was notable however that the clinically important
      improvement in terms of pain, functional disability, quality of life, and SWT in
      both groups was achieved within the first two weeks, which was maintained at one
      year follow-up. CONCLUSIONS: It is feasible to conduct a main RCT, to compare
      different frequencies of acupuncture for LBP, using sensitive measurements. Also
      the trend for early clinically important improvement within a minimum of four
      measurements is worthy of further study.

PMID- 19398067
TI  - Myelophil, an extract mix of Astragali Radix and Salviae Radix, ameliorates
      chronic fatigue: a randomised, double-blind, controlled pilot study.
AB  - OBJECTIVES: To investigate the anti-fatigue effects of Myelophil, an extract of a
      mix of Astragali Radix and Salviae Radix, which has been used to treat patients
      with chronic fatigue. SUBJECTS AND DESIGN: A randomised, double-blind, controlled
      clinical trial was performed with 36 adults who complained of chronic fatigue.
      The subjects were divided among a control group and low- and high-dose groups (3
      or 6g of oral Myelophil per day, respectively) and were monitored for 4 weeks.
      Fatigue severity was subjectively characterised, and the expression of 42
      cytokines was evaluated using an antibody array. RESULTS: Myelophil
      administration (3g per day) significantly decreased the fatigue severity score
      compared with the control (p<0.05). No changes were noted in cytokine expression.
      CONCLUSIONS: Myelophil appears to have a pharmacological effect against fatigue,
      suggesting the clinical relevance of the traditional medicinal plants, Astragalus
      membranaceus and Salvia miltiorrhiza.

PMID- 19398068
TI  - Current status of Kampo (Japanese herbal) medicines in Japanese clinical practice
      guidelines.
AB  - BACKGROUND AND AIMS: Kampo (Japanese herbal) medicines are often used in clinical
      practice in Japan. However, it is unclear how Kampo medicines are quoted and
      evaluated in current clinical practice guidelines (CPGs). Here, we systematically
      reviewed Japanese CPGs, and aimed to reveal how Kampo medicines are described in
      the CPGs. MATERIALS AND METHODS: We reviewed the quasi-comprehensive list of
      Japanese CPGs available from the Toho University Medical Media Center (TUMMC)
      having the largest data base on Japanese CPGs, and also used a hand search. CPGs
      containing Kampo products were classified into three types based on how Kampo was
      handled. CPGs that provided recommendations based on evidence were classified as
      "type A". Those which cited references but did not provide any recommendations
      were classified as "type B". Those which described the Kampo practice or Kampo
      related terms without providing any relevant references were classified as "type
      C". RESULTS: By the end of March of 2007, 35 (10.1%) of 346 CPGs listed by TUMMC
      contained descriptions of Kampo products. We discovered one Kampo-related CPGs in
      a hand search process. Of these 36 CPGs, 6 were "type A", 13 were "type B", and
      17 were "type C". Although results from pertinent randomized controlled trials
      (RCTs) were available, we noticed that some well-known RCTs studying Kampo
      medicines are missing in corresponding CPGs. CONCLUSIONS: We revealed that the
      citation rate of Kampo medicines in CPGs was approximately 10% and that some
      pivotal trials for Kampo medicines were not quoted in CPGs. Kampo medicines in
      CPGs should be assessed more comprehensively and scientifically.

PMID- 19398069
TI  - Primary dysmenorrhoea: a comparative study on Australian and Chinese women.
AB  - OBJECTIVE: To explore the extent to which traditional Chinese medicine (TCM)
      diagnostic categories for primary dysmenorrhoea are useful in describing the
      clinical presentation of this condition in Australian women in comparison with
      Chinese women, and therefore the potential usefulness of these categories in
      guiding TCM treatment of Australian women. DESIGN AND SETTING: A comparative
      study of 120 Australian and 122 Chinese women aged from 18 to 45 years with
      primary dysmenorrhoea. MAIN OUTCOME MEASURES: Modified valid TCM diagnostic
      protocol. RESULTS: Difference in menstruation and menstrual pain profiles between
      the two groups of women found in the same study did not translate into
      differences in the underlying syndrome according to TCM diagnostic categories.
      The study found that Australian and Chinese women were represented in broadly
      similar proportions across the defined five diagnostic categories. CONCLUSION:
      Some evidence suggests that although the clinical presentation of symptoms in
      Australian and Chinese women is different, the distribution of women across the
      diagnostic categories in TCM is similar. Therefore, the TCM protocol used to
      diagnose primary dysmenorrhoea and guide treatment is unlikely to require
      adaptation for use with Australian women.

PMID- 19398070
TI  - Effects of complementary eurythmy therapy on heart rate variability.
AB  - BACKGROUND: The importance of mind-body oriented therapies in oncology has
      increased in recent years. Eurythmy therapy (EYT, Greek: eurythmy=harmonious
      rhythm) is a mind-body oriented therapy used in Anthroposophic Medicine. EYT can
      lead to long-term alleviation of chronic disease symptoms and improve patient
      quality of life. Yet, little is known about underlying physiological mechanisms.
      OBJECTIVE: This study aims to compare the effects of EYT and conventional
      ergometer training (CET) on heart rate variability (HRV). DESIGN: In a cross-over
      design, 20 healthy subjects performed two different EYT exercises and two
      sessions of CET. ECGs were recorded throughout these procedures. HRV was
      quantified by the extent of very low (VLF), low (LF) and high frequency (HF)
      oscillations of heart rate. RESULTS: VLF and LF oscillations increased during one
      EYT exercises when compared to rest after EYT ('B exercise', VLF: 7.65 vs. 6.57
      log ms(2); LF: 8.06 vs. 6.15 log ms(2)) whereas during the other EYT exercise
      only LF increased ('L exercise', LF: 7.19 vs. 6.25 log ms(2)). HF was not
      affected. During CET VLF, LF and HF decreased compared to rest (VLF: 5.4 log
      ms(2), LF: 4.5 log ms(2), HF: 3.2 log ms(2)). During rest after both EYT
      exercises LF/HF decreased when compared to rest after CET (0.4 and 0.5 vs. 1.4).
      CONCLUSION: At comparable workloads, EYT stimulated HRV whereas CET attenuated
      HRV. The decrease of LF/HF during rest after EYT indicates an improved
      relaxation. These results suggest that patients may benefit from EYT in terms of
      HRV improvement.

PMID- 19398071
TI  - A typology of negative responses: a case study of shiatsu.
AB  - OBJECTIVE: To develop and apply a client-centred typology for classifying
      negative responses to a CAM therapy. DESIGN: Prospective, 6 months cohort,
      pragmatic study of the effects and experience of shiatsu within three countries
      (Austria, Spain and the UK). Data collected via postal questionnaires, including
      on client-perceived negative responses. Classification of negative responses
      situated within a theoretical framework of Zen or Masunaga model of shiatsu.
      INTERVENTIONS: Shiatsu as delivered by the practitioner in routine practice. MAIN
      OUTCOME MEASURES: Prevalence of negative responses and response types. RESULTS:
      633 clients provided full follow-up data, a response rate of 67%. A prevalence
      rate of 12-22 per 100 of client-perceived 'negative responses' was found across
      the three countries. Transitional effects accounted for 82% of all the client
      described 'negative' responses. Nine clients (1.4% of the total), relating to 10
      sets of written comments, reported a negative response that was classified as 'a
      potentially adverse event or effect' that might represent a risk to client
      safety. None of these clients ceased shiatsu. CONCLUSIONS: A typology of negative
      responses has an important role for practitioners, clients and researchers in
      drawing up evidence on the safety of a therapy. For researchers and policy
      makers, use of such a typology informs insight into what might cause harm (that
      is, 'definite' adverse events). For clients, the typology takes seriously the
      clients' own view. For practitioners, the typology draws on the modality's
      guiding theory and suggests ways to improve the delivery of treatments. Applying
      the typology to a cross-European prospective study of shiatsu supports the
      argument of shiatsu being inherently a safe modality.

PMID- 19398072
TI  - Kava Anxiety Depression Spectrum Study (KADSS): a mixed methods RCT using an
      aqueous extract of Piper methysticum.
AB  - OBJECTIVES: To report on the design, significance and potential impacts of the
      first documented human clinical trial assessing the anxiolytic and thymoleptic
      efficacy of an aqueous mono-extract of Piper methysticum (kava). The significance
      of the qualitative element of our clinical trial is also explored. The Kava
      Anxiety Depression Spectrum Study (KADSS) is a 3-week placebo-controlled, double
      blind, cross-over trial involving 60 adult participants (18-65) with elevated
      stable anxiety and varying levels of depressive symptoms. AIMS: The aims of KADSS
      are: (1) to determine whether an aqueous standardised extract of kava is
      effective for the treatment of anxiety; (2) to assess the effects of kava on
      differing levels of depression; and (3) to explore participants' experience of
      taking kava via qualitative research. The study also provides preliminary
      assessment of the safety of an aqueous extract of kava in humans. CONCLUSION: If
      results reveal that the aqueous kava preparation exerts significant anxiolytic
      effects and appears safe, potentially beneficial impacts may occur. Data
      supporting a safe and effective kava extract may encourage a re-introduction of
      kava to Europe, UK and Canada. This may provide a major socioeconomic benefit to
      Pacific Island nations, and to sufferers of anxiety disorders.

PMID- 19398073
TI  - Integrated medicine: the best of both worlds or the worst for our patients?

PMID- 19398075
TI  - Depression and disease severity as predictors of health-related quality of life
      in patients with chronic heart failure--a structural equation modeling approach.
AB  - BACKGROUND: To examine whether depression and heart failure severity are
      independent predictors of both the physical and psychologic domains of health
      related quality of life (HRQoL) in patients with chronic heart failure. METHODS
      AND RESULTS: A sample of 206 outpatients with chronic heart failure (mean age 64
      years, 69% male) was evaluated. Depression was measured with the Patient Health
      Questionnaire and disease-specific HRQoL with the Kansas City Cardiomyopathy
      Questionnaire. Heart failure severity was assessed with physician ratings of the
      New York Heart Association (NYHA) functional class. The simultaneous effects of
      predictor variables on outcomes were estimated using structural equation
      modeling. Both depression and NYHA functional class independently predicted the
      physical domain of HRQoL. By contrast, the psychologic domain was only predicted
      by depression, but not by NYHA functional class. CONCLUSIONS: Our results suggest
      that comorbid depression has an independent impact on both physical and
      psychologic HRQoL in patients with chronic heart failure after controlling for
      the severity of heart failure symptoms, while heart failure severity only impacts
      physical HRQoL. Thus, assessment of comorbid depression may help interpreting
      reduced HRQoL in heart failure patients. Research seems warranted evaluating
      whether the amelioration of depression may enhance patients' HRQoL in chronic
      heart failure.

PMID- 19398074
TI  - Prevalence and physiological predictors of sleep apnea in patients with heart
      failure and systolic dysfunction.
AB  - BACKGROUND: Previous studies reported high prevalences of obstructive and central
      sleep apnea (OSA and CSA, respectively) in patients with heart failure (HF).
      However, these preceded widespread use of beta-blockers and spironolactone that
      might have reduced their prevalences. We therefore determined, in patients with
      HF, prevalences and predictors of OSA and CSA and the influence of changes in HF
      therapy on prevalences. METHODS AND RESULTS: A total of 218 HF patients with left
      ventricular ejection fraction (LVEF) <or=45% underwent sleep studies between 1997
      and 2004 and were classified as having moderate to severe sleep apnea (apnea
      hypopnea index >or=15 hours of sleep, either OSA or CSA), or mild to no sleep
      apnea. The prevalence of moderate to severe OSA was 26% and of CSA was 21%.
      Predictors of OSA were older age, male sex, and greater body mass index, and of
      CSA were older age, male sex, atrial fibrillation, hypocapnia, and diuretic use.
      Between 1997 and 2004, the prevalences of OSA and CSA did not change
      significantly (P(trend) =.460, P(trend) =.211, respectively) despite increased
      use of beta-blockers and spironolactone (P(trend) < .001, P(trend) < .001,
      respectively), and an increase in LVEF (P(trend)=.005). CONCLUSIONS: OSA and CSA
      remain common in patients with HF, despite increases in beta-blocker and
      spironolactone use.

PMID- 19398076
TI  - Reduction in BNP levels with treatment of decompensated heart failure and future
      clinical events.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) levels correlate with outcomes in
      patients with heart failure (HF). We sought to compare the relationship between
      absolute and relative changes in BNP with future clinical events, and whether
      serial BNP measurements add prognostic information in patients treated for
      decompensated HF. METHODS AND RESULTS: In 203 patients treated for HF, increasing
      tertiles of BNP levels after treatment had a hazard ratio of 1.4 (1.1-1.7, P <
      .01) and increasing tertiles of percent reduction in BNP, had a hazard ratio of
      0.7 (0.6-0.9, P = .005), respectively, for the combined end point of total
      mortality or readmission for HF. Higher baseline BNP levels did not decrease to
      lower BNP levels as often as lower BNP levels (P < .001). Follow-up BNP performed
      better in a model, incorporating age, ejection fraction, prior HF
      hospitalization, New York Heart Association Class, race, use of beta-blockers and
      renin-angiotensin axis inhibitors and renal insufficiency, than did baseline BNP
      or percent reduction in BNP. More BNP measurements other than the follow-up BNP
      did not improve the fit of the model further. CONCLUSIONS: These results suggest
      that both lower absolute BNP levels and greater percentage reduction in BNP with
      treatment of decompensated HF are associated with better event-free survival.
      Advocating a threshold BNP to which patients should be treated may not be
      possible given that high BNP levels tend not to decrease to levels associated
      with better outcomes during the short period of treatment. More BNP measurements
      do not add prognostic information beyond that provided by a single BNP level
      after treatment.

PMID- 19398077
TI  - Clinical characteristics of acute decompensated heart failure with rapid onset of
      symptoms.
AB  - BACKGROUND: Few reports regarding the definition, epidemiology, and
      pathophysiology of acute decompensated heart failure (ADHF) are available. The
      clinical characteristics of 194 consecutive ADHF patients with abrupt onset of
      symptoms were investigated. METHODS AND RESULTS: Patients with acute coronary
      syndromes including acute myocardial infarction, acute pneumonia, severe valvular
      disease, and end-stage renal disease that required dialysis therapy were
      excluded. Patients were divided into 2 groups: rapid-progression group, onset
      within 24 hours before admission (n = 78); and gradual-progression group, onset
      more than 24 hours before admission (n = 52). No significant differences were
      observed in the age, gender, prescriptions, and hematological data between the 2
      groups. The proportion of patients who drank excessive water was higher in the
      rapid-progression group. Systolic blood pressure, diastolic blood pressure, heart
      rate, left ventricular ejection fraction, and left ventricular wall thickness
      were greater in patients in the rapid-progression group. Indexes indicating left
      ventricular diastolic function were significantly deteriorated in the rapid
      progression group. CONCLUSION: Excessive water intake, acute hypertension, and
      diastolic dysfunction are associated with the pathophysiology of abrupt-onset
      ADHF. Hypertensive patients with diastolic dysfunction should be treated
      cautiously to prevent the occurrence of ADHF.

PMID- 19398078
TI  - Heart failure due to systolic dysfunction and mortality in diabetes: pooled
      analysis of 39,505 subjects.
AB  - BACKGROUND: Despite recent successes in improving mortality from congestive heart
      failure (CHF) with drugs and devices, several reports suggest increased mortality
      among CHF subjects with diabetes. Our objective was to conduct a meta-analysis to
      determine aggregate risk of mortality and hospitalization in CHF from systolic
      dysfunction and diabetes. METHODS AND RESULTS: Observational and randomized
      trials reporting on CHF and mortality in diabetes since 2001 were identified
      through MEDLINE and Cochrane database searches and hand searching of cross
      references. Minimum follow-up of the study cohort should have been at least 6
      months. Studies with very small sample size (n < 200) were excluded. Major
      outcome measure of mortality and secondary outcome measure of CHF hospitalization
      were extracted from published results. Analysis was done for composite mortality
      and hospitalization risk, heterogeneity, robustness, and publication bias. A
      total of 17 trials (n = 39,505 subjects) were eligible. There were a total of
      10,068 deaths, with 3615 among diabetics, from available data. The relative risk
      was significantly higher for diabetics by 28% (95% CI 1.22-1.34, P < .0001).
      Similarly pooled relative risk for hospitalization was significantly higher for
      diabetics by 36% (95% CI 1.26-1.48, P < .0001). Heterogeneity was present (P <
      .01) and accounted for by observational studies. There was no significant
      publication bias and lack of robustness was not obvious. CONCLUSIONS: Aggregate
      mortality and recurrent hospitalization risk for diabetic subjects with CHF is
      28% and 36% higher than for nondiabetic subjects. Future trials should
      specifically focus on improving survival in these subjects.

PMID- 19398079
TI  - The influence of renal function on clinical outcome and response to beta-blockade
      in systolic heart failure: insights from Metoprolol CR/XL Randomized Intervention
      Trial in Chronic HF (MERIT-HF).
AB  - BACKGROUND: Limited information is available on the risk and impact of renal
      dysfunction on the response to beta-blockade and mode of death in systolic heart
      failure (HF). METHODS AND RESULTS: Renal function was estimated with glomerular
      filtration rate (eGFR) using the simplified Modification of Diet in Renal Disease
      (MDRD) equation. Patients from the Metoprolol CR/XL Controlled Randomized
      Intervention Trial in Chronic HF (MERIT-HF) were divided into 3 renal function
      subgroups (MDRD formula): eGFR(MDRD) > 60 (n = 2496), eGFR(MDRD) 45 to 60 (n =
      976), and eGFR(MDRD) < 45 mL/min per 1.73 m(2) body surface area (n = 493).
      Hazard ratio (HR) was estimated with Cox proportional hazards models adjusted for
      prespecified risk factors. Placebo patients with eGFR < 45 had significantly
      higher risk than those with eGFR > 60: HR for all-cause mortality, 1.90 (95%
      confidence interval [CI], 1.28 to 2.81) comparing placebo patients with eGFR < 45
      and eGFR > 60, and for the combined end point of all-cause
      mortality/hospitalization for worsening HF (time to first event): HR, 1.91 (95%
      CI, 1.44 to 2.53). No significant increase in risk with deceased renal function
      was observed for those randomized to metoprolol controlled release (CR)/extended
      release (XL) due to a highly significant decrease in risk on metoprolol CR/XL in
      those with eGFR < 45. For total mortality, metoprolol CR/XL vs placebo: HR, 0.41
      (95% CI. 0.25 to 0.68; P < .001) in those with eGFR < 45 compared with HR, 0.71
      (95% CI, 0.54 to 0.95; P < .021) for those with eGFR > 60; corresponding data for
      the combined end point was HR, 0.44 (95% CI, 0.31 to 0.63; P < .0001) and HR,
      0.75 (0.62 to 0.92; P = .005, respectively; P = .095 for interaction by treatment
      for total mortality; P = .011 for combined end point). Metoprolol CR/XL was well
      tolerated in all 3 renal function subgroups. CONCLUSIONS: Renal function as
      estimated by eGFR was a powerful predictor of death and hospitalizations from
      worsening HF. Metoprolol CR/XL was at least as effective in reducing death and
      hospitalizations for worsening HF in patients with eGFR < 45 as in those with
      eGFR > 60.

PMID- 19398080
TI  - Prolonged electrical muscle stimulation exercise improves strength, peak VO2, and
      exercise capacity in patients with stable chronic heart failure.
AB  - BACKGROUND: Exercise training can help patients with chronic heart failure but
      may be limited in its applicability due to age and other comorbidities. This
      investigation evaluated training responses to prolonged electrical muscle
      stimulation (EMS) in patients with stable chronic heart failure. METHODS AND
      RESULTS: In a crossover designed study, 10 patients (age 66 +/- 6.5 years, 9
      male) were randomized to 8 weeks of training or habitual activity before crossing
      over to the other limb after a washout period of 2 weeks. Training consisted of
      electrical muscle stimulation of the major leg muscles for a minimum of 1 hour, 5
      days a week. Peak oxygen consumption, 6-minute walking distance test, body mass
      index, and quadriceps muscle strength were the end points. At baseline the mean
      values for peak oxygen consumption (VO(2)), 6-minute walking distance, quadriceps
      strength, and body mass index were 19.5 +/- 3.5 mL x kg x min, 415.1 +/- 56.6m,
      377.9 +/- 110.4N, and 27.9 +/- 3.1 kg/m(2), respectively. After training, peak
      VO(2) increased to 21.2 +/- 5.1 mL x kg x min (P < .05), walking distance
      increased to 454.9 +/- 54.5M (P < .005), quadriceps strength increased to 404.9
      +/- 108.6N (P < .005), whereas we did not observe a significant effect on body
      mass index (P > .05). CONCLUSIONS: EMS can be used in sedentary adults with
      stable chronic heart failure to improve physical fitness and functional capacity.
      It may provide a viable alternative for patients unable to undertake more
      conventional forms of exercise.

PMID- 19398081
TI  - Improvement in left ventricular diastolic stiffness induced by physical training
      in patients with dilated cardiomyopathy.
AB  - BACKGROUND: Diastolic dysfunction in long-term heart failure is accompanied by
      abnormal neurohormonal control and ventricular stiffness. The diastolic phase is
      determined by a balance between pressure gradients and intrinsic ventricular wall
      properties: according to a mathematical model, the latter (ie, left ventricular
      [LV] elastance, K(LV)) may be calculated by the formula: K(LV) = (70/[DT-20])(2)
      mm Hg/mL, where DT is the transmitral Doppler deceleration time. METHODS AND
      RESULTS: In 54 patients with chronic systolic heart failure (39 men, 15 women;
      age 65 +/- 10 years; New York Heart Association [NYHA], 2.3 +/- 0.9; ejection
      fraction [EF], 32% +/- 5%), we analyzed the relationship between K(LV) and an
      index of neurohormonal derangement (levels of brain natriuretic peptide [BNP]),
      and investigated whether 3 months of physical training could modulate diastolic
      operating stiffness. Patients were randomized to physical training (n = 27) or to
      a control group (n = 27). Before and after training, patients underwent Doppler
      echocardiogram and cardiopulmonary stress test. At baseline, ventricular
      stiffness was related to BNP levels (P < .01). Training improved NYHA class,
      exercise performance, and estimated pulmonary pressure. BNP was reduced.
      Ventricular volumes, mean blood pressure, and EF remained unchanged. A 27%
      reduction of elastance was observed (K(LV), 0.111 +/- 0.044 from 0.195 +/- 0.089
      mm Hg/mL; P < .01), whose magnitude was related to changes in BNP (P < .05) and
      to K(LV) at baseline (P < .01). No changes in K(LV) were observed in controls
      after 3 months (0.192 +/- 0.115 from 0.195 +/- 0.121 mm Hg/mL). CONCLUSIONS: In
      heart failure, left ventricular diastolic stiffness is related to neurohormonal
      derangement and is modified by physical training. This improvement in LV
      compliance could result from a combination of hemodynamic improvement and
      regression of the fibrotic process.

PMID- 19398082
TI  - Accelerometer-based quantification of 6-minute walk test performance in patients
      with chronic heart failure: applicability in telemedicine.
AB  - BACKGROUND: Distance walked in the 6-minute walk test (6MWT) is an important
      prognostic parameter used clinically to assess functional status in patients with
      chronic heart failure (CHF). In this study, we investigated if alternative
      performance parameters with similar prognostic value can be gained from
      accelerometers. METHODS AND RESULTS: Fifty CHF patients (age, 60.9 +/- 14.0
      years) were asked to perform a 6MWT while wearing 2 accelerometers and 1
      pedometer. Total 6MWT step frequency (SF) and activity counts (VMU) were
      correlated to 6MWT distance. The accelerometer was highly accurate at quantifying
      SF (detected vs. observed: r = 0.99; P < .001), whereas the pedometer was
      unreliable below 50 m/min. VMU increased linearly with walking speed (r = 0.99),
      and both SF and VMU correlated strongly with 6MWT distance (VMU: r = 0.91; SF: r
      = 0.87, respectively; P < .001) and each other (r = 0.80, P < .001). CONCLUSIONS:
      Accelerometers are reliable in measuring physical performance during the 6MWT in
      CHF patients. Besides the simple acquisition of 6MWT distance currently used for
      patient assessment, accelerometers provide new data that might be useful to
      evaluate exercise performance during the 6MWT. This allows for routine assessment
      of exercise capacity in a home-based setting in the context of telemedicine.

PMID- 19398083
TI  - Selective treatment algorithm for mitral valve annuloplasty in nonischemic
      functional mitral regurgitation.
AB  - BACKGROUND: The success rate of mitral annuloplasty (MA) for functional mitral
      regurgitation (FMR) varies. This study evaluated the effectiveness of this
      procedure in nonischemic dilated cardiomyopathy (DCM) patients after a selective
      treatment protocol was followed. METHODS AND RESULTS: This study analyzed 42
      patients with nonischemic DCM and FMR (mean regurgitation grade, 3.6 +/- 0.3),
      aged a mean 56.5 +/- 15 years (range, 25 to 78 years), who underwent MA from
      April 2003 to December 2007. The analysis excluded patients with coronary artery
      disease, or mitral leaflets or subvalvular pathologies. All patients had taken
      maximal medications for at least 3 months and were still in New York Heart
      Association (NYHA) functional class III to IV (mean, 3.2 +/- 0.4). Mean ejection
      fraction (EF) was 31.4% +/- 12.9% (range, 8% to 58%), and left ventricular end
      diastolic diameter (LVEDD) was 66.0 +/- 8.3 mm (range, 55 to 85 mm). Downsized
      Carpentier Physio ring (Carpentier-Edwards, Irvine, California) annuloplasty,
      mean size 26.3 +/- 2.3 (range, 24 to 30), was the preferred procedure.
      Concomitant procedures included 23 tricuspid valve repairs and 10 Maze operations
      for atrial fibrillation. Echocardiography was performed at early (<or=3 months;
      mean 1.6 +/- 1.5), short-term (6 to 12 months; mean 6.9 +/- 3.4), and midterm
      (>12 months; mean 29.5 +/- 13.4 months) follow-up. All late deaths and
      readmissions were recorded. One (2.4%) in-hospital death occurred due to low
      cardiac output. Follow-up was completed in 40 of 41 (97.6%) patients (mean
      duration, 31.9 +/- 16.1; range, 3.9 to 59.2 months). Eight (19.5%) patients were
      readmitted for heart failure, including 2 late MRs due to ring dehiscence and
      infective endocarditis. Three of 5 deaths during the follow-up period were
      attributed to cardiac death. Actuarial survival after 1 and 3 years was 88.9% and
      79.2%, respectively. The number of patients treated with beta-blockers increased
      after operation, from 52.4% to 75.6% (P = .028). NYHA class decreased from 3.2 +/
      0.4 to 1.3 +/- 0.6 (P < .0001). Echo examination revealed left heart reverse
      remodeling and improved performance in all follow-up time frames. CONCLUSION:
      This study shows that MA in patients with non-ischemic DCM and FMR is feasible
      and associated with reasonable short and long term outcomes.

PMID- 19398084
TI  - Value of the paced QRS duration.
AB  - BACKGROUND: The value for paced QRS duration (pQRSd) to detect left ventricular
      (LV) dysfunction in right ventricular apex (RVA)-paced patients has not been
      evaluated. METHODS AND RESULTS: A total of 272 RVA-paced patients, including 99
      with LV systolic dysfunction (LVSD) and 173 without LVSD, were enrolled in this
      study. The pQRSd, echocardiographic variables, and plasma N-terminal pro-brain
      natriuretic peptide (NT-proBNP) levels were measured. Relationships between pQRSd
      and echocardiographic variables, NT-proBNP levels, and New York Heart Association
      (NYHA) functional classification were analyzed. pQRSd was correlated with LV end
      diastolic and end-systolic dimensions (beta = 1.59 and 1.54, respectively; all P
      < .001), NT-proBNP levels (beta = 12.98, P < .001) and LV ejection fraction (beta
      = -109.25, P < .001). There was a stepwise increase in pQRSd with increasing NYHA
      Class (all P < .001). The pQRSd cutoff value of 200 ms, derived from the receiver
      operator characteristic curve, had sensitivity of 71.72% and specificity of
      86.71% to detect LVSD. pQRSd >or= 240 ms gave a positive predictive value of
      100%, whereas <180 ms excluded >97.3% of patients with LVSD. CONCLUSIONS: In RVA
      paced patients, pQRSd is correlated with left ventricular structures and function
      and pQRSd of 200 ms is a satisfactory cutoff value in terms of sensitivity and
      specificity for detecting LVSD.

PMID- 19398085
TI  - The potential role of erythropoietin in chronic heart failure: from the
      correction of anemia to improved perfusion and reduced apoptosis?
AB  - Besides stimulating erythropoiesis, erythropoietin (EPO) exerts powerful
      proangiogenic and antiapoptotic effects. These erythropoiesis-independent effects
      are potentially useful as a supplement for the treatment of chronic heart failure
      (CHF). EPO may improve microvascular capacity of ischemic myocardial tissue and
      could thereby (partially) restore myocardial function. In addition, EPO could
      protect cardiomyocytes from hypoxic damage and prevent them from apoptosis.
      However, the clinical value of these erythropoiesis-independent effects for the
      treatment of CHF remains to be elucidated. Small-sized trials evaluating the
      effects of EPO treatment on surrogate endpoints in patients with CHF showed
      positive effects in general; however, their mutual results are not always
      unambiguous. Moreover, increasing hematocrit levels with EPO has been associated
      with increased blood viscosity and an inherent risk of thromboembolic events. A
      currently running multicenter phase III trial is designed to provide clarity
      concerning the effects of EPO on outcome and safety in patients with CHF.
      Focusing primarily on outcome, however, does not provide insight into the mode of
      action and isolated benefits of the erythropoiesis-independent effects of EPO.
      Further exploration of these effects is a key issue to gain knowledge of the full
      potential of EPO for the treatment of CHF.

PMID- 19398086
TI  - Increased high mobility group box-1 protein levels are associated with impaired
      cardiopulmonary and echocardiographic findings after acute myocardial infarction.
AB  - BACKGROUND: Several markers of systemic inflammation seem to play an active role
      in the pathophysiology of acute coronary syndrome and its evolution. High
      mobility group box-1 (HMGB-1), a ubiquitous nuclear protein constitutively
      expressed in quiescent cells, was recently recognized as a newer critical
      mediator of inflammatory diseases. The present study aimed to evaluate the
      possible association between HMGB-1 levels and structural and functional indices
      of cardiovascular performance such as cardiopulmonary and Doppler
      echocardiography indices in patients after acute myocardial infarction (MI).
      METHODS AND RESULTS: Fifty-four consecutive patients (mean age 58.3 years, 83%
      males) recovering from acute MI were included in the study protocol. All patients
      underwent Doppler-echocardiography, cardiopulmonary exercise, and HMGB-1 assay.
      HMGB-1 levels in acute MI patients were significantly higher compared with age-
      and body mass index-matched controls (14.8 +/- 6.8 vs. 2.3 +/- 1.0 ng/mL, P <
      .0001, respectively). Postinfarction patients showed oxygen consumption at peak
      exercise (VO(2 peak)) = 14.4 +/- 4.2 mL x kg x min and a slope of increase in
      ventilation over carbon dioxide output (VE/VCO(2 slope)) = 32.1 +/- 6.2, whereas
      Doppler-echocardiography values were: left ventricular end-diastolic volume
      (LVEDV) = 53.4 +/- 8.2 mL/m(2); left ventricular ejection fraction (LVEF) = 41.7
      +/- 7.0%. Multiple linear regression analysis (stepwise method) showed that VO(2
      peak) (beta = -0.276, P = .012), VE/VCO(2 slope) (beta = 0.244, P = .005), LVEDV
      (beta = 0.267, P = .018), peak creatine kinase-MB (beta = 0.339, P = .004), peak
      Troponin I (beta = 0.244, P = .002), and LVEF (beta = -0.312, P = .021) were
      significantly associated with HMGB-1 levels. CONCLUSIONS: The present study
      demonstrated that in postinfarction patients, HMGB-1 levels were significantly
      higher compared with controls, and significantly correlated with cardiopulmonary
      and Doppler-echocardiography parameters.

PMID- 19398088
TI  - Standardized clinical data collection and agreed outcome measurement.

PMID- 19398087
TI  - Decreased immune responses to influenza vaccination in patients with heart
      failure.
AB  - BACKGROUND: Heart failure (HF) patients are at risk for influenza despite
      widespread vaccination. Both humoral (antibody) and cytotoxic T-lymphocyte (CTL)
      responses are important for protection. We explored antibody- and CTL-mediated
      responses to the influenza vaccine in HF patients compared with healthy controls.
      METHODS AND RESULTS: We studied 29 HF patients (9 ischemic, 20 nonischemic)
      stable on HF therapies and 17 healthy controls. Participants had phlebotomy
      before and after influenza vaccination. Antibody production was measured in serum
      by hemagglutination inhibition assay and CTL responses (via interferon [IFN]
      gamma and interleukin [IL]-10 production) were measured in isolated peripheral
      blood mononuclear cells with enzyme-linked immunosorbent assay. CTL responses
      demonstrated increased IL-10 production in HF patients after vaccination (P =
      .002), but similar IFN-gamma responses to healthy controls. All participants
      demonstrated antibody seroprotection; groups had similar rates of seroconversion
      (P = NS). Antibody-mediated response to the newest vaccine antigen, H3N2, was
      reduced in HF (P = .009). CONCLUSIONS: Patients with HF had higher vaccine
      induced IL-10 concentrations, suggesting a different CTL phenotype for vaccine
      responses. HF patients did not mount as vigorous of an antibody immune response
      to the newest vaccine viral strain compared with healthy individuals. These data
      suggest that immunologic memory may be important for vaccine protection in HF
      patients.

PMID- 19398089
TI  - Diagnostic accuracy of transvaginal sonography for the diagnosis of adenomyosis:
      systematic review and metaanalysis.
AB  - OBJECTIVE: The purpose of this study was to critically appraise the diagnostic
      accuracy of transvaginal sonography for diagnosing adenomyosis. STUDY DESIGN:
      Computerized databases were used to identify relevant reports published between
      1966 and 2007 reporting data on the accuracy of transvaginal sonography for
      diagnosing adenomyosis in women having hysterectomy. The presence or absence of
      adenomyosis was confirmed by histopathologic analysis of hysterectomy specimens.
      The total analysis included 14 trials with 1895 aggregate participants. Two
      authors independently assessed methodological quality and constructed tables for
      the assessment of diagnostic measures. RESULTS: Transvaginal ultrasound predicted
      adenomyosis with a likelihood ratio of 4.67 (95% confidence interval [CI], 3.13
      6.17). The overall prevalence of adenomyosis was 27.9% (95% CI, 25.5-30.3). The
      probability of adenomyosis with an abnormal transvaginal ultrasound was 66.2%
      (95% CI, 61.6- 70.6). The probability of adenomyosis with a normal transvaginal
      ultrasound was 9.1% (95% CI, 7.3-11.1). CONCLUSION: Transvaginal sonography
      appears to be an accurate diagnostic test for adenomyosis.

PMID- 19398090
TI  - Herceptin (trastuzumab) therapy in a twin pregnancy with associated
      oligohydramnios.
AB  - Herceptin (trastuzumab) is an adjuvant chemotherapy agent used in treatment of
      certain breast cancers. Limited information is available on the use of herceptin
      in pregnancy. This case is a twin pregnancy exposed to herceptin until 23 weeks'
      gestation. One twin had chronic renal failure develop, whereas the other twin did
      not.

PMID- 19398091
TI  - Unexpected finding in a pelvic mass: imaging suggested an ovarian malignancy.

PMID- 19398092
TI  - Evaluation of different add-back estradiol and progesterone treatments to
      gonadotropin-releasing hormone agonist treatment in patients with premenstrual
      dysphoric disorder.
AB  - OBJECTIVE: The aim of this study was to investigate which add-back hormone
      replacement therapy would be most beneficial in terms of mood effects for
      patients with premenstrual dysphoric disorder who are receiving gonadotropin
      releasing hormone agonist therapy. STUDY DESIGN: Three different add-back hormone
      replacement treatments were evaluated in a randomized, double-blinded, cross-over
      clinical trial in 27 patients premenstrual dysphoric disorder. The add-back
      treatments consisted of 1.5 mg estradiol and 400 mg progesterone, 1.5 mg
      estradiol and placebo, and 0.5 mg estradiol and 400 mg progesterone. The primary
      outcome measure was daily symptom ratings for mood and physical symptoms.
      RESULTS: The highest dose of estradiol in combination with progesterone was
      associated with the most pronounced symptom recurrence, both in comparison with a
      lower dose of estradiol together with progesterone and estradiol-only treatment.
      CONCLUSION: Based on the findings of the present study, long-cycle add-back
      treatment to avoid frequent progestagen use appears to be most beneficial for
      patients with premenstrual dysphoric disorder.

PMID- 19398093
TI  - Intramembranous solute and water fluxes during high intramembranous absorption
      rates in fetal sheep with and without lung liquid diversion.
AB  - OBJECTIVE: To examine mechanisms that mediate increased intramembranous solute
      and water absorption. STUDY DESIGN: Intramembranous solute and water fluxes were
      measured in fetal sheep under basal conditions and after intraamniotic infusion
      of lactated Ringer's solution of 4 L/d for 3 days with and without lung liquid
      diversion. RESULTS: Intramembranous sodium, potassium, chloride, calcium,
      glucose, and lactate fluxes increased 2.5- to 7.9-fold, were linearly related to
      volume fluxes (r = 0.83-0.99), and were unaffected by lung liquid. All clearance
      rates, except that of lactate, increased to equal the intramembranous volume
      absorption rate during infusion. CONCLUSION: Under basal conditions, passive
      diffusion makes a minor and bulk flow a major contribution to intramembranous
      solute absorption. During high absorption rates, the increase in solute
      absorption above basal levels appears to be due entirely to bulk flow and is
      unaffected by lung liquid. The increased bulk flow is consistent with vesicular
      transcytosis.

PMID- 19398094
TI  - Rapid human immunodeficiency virus testing in obstetric outpatient settings: the
      MIRIAD study.
AB  - OBJECTIVE: To evaluate the acceptability and feasibility of rapid human
      immunodeficiency virus testing in obstetric outpatient settings. STUDY DESIGN:
      The Mother-Infant Rapid Intervention at Delivery (MIRIAD) study was a
      prospective, multicenter study. Women were offered rapid and conventional human
      immunodeficiency virus testing if they presented to outpatient settings late in
      pregnancy with undocumented human immunodeficiency virus status. We compared
      median times between conventional and rapid testing and between rapid point-of
      care and rapid laboratory-based testing. RESULTS: Among eligible women who were
      offered participation, 90% accepted testing. The median time from blood draw to
      result available was faster for rapid testing (25 minutes) than conventional
      testing (23 hours; P < .0001). For rapid tests, point-of-care testing was faster
      than laboratory-based testing (24 minutes vs 35 minutes; P < .0001). Almost 96%
      of rapid test results were available within 1 hour. CONCLUSION: Rapid human
      immunodeficiency virus testing is acceptable, feasible, and provides results far
      sooner than conventional testing in obstetric outpatient settings.

PMID- 19398095
TI  - Extended-field radiation therapy with whole pelvis radiotherapy and cisplatin
      chemosensitization in the treatment of IB2-IIIB cervical carcinoma: a
      retrospective review.
AB  - OBJECTIVE: This retrospective study evaluated the toxicity of extended-field
      radiation therapy (EFRT), whole pelvis radiotherapy, and concurrent chemotherapy
      in patients treated with IB2-IIIB cervical carcinoma. STUDY DESIGN: Patients
      treated with EFRT, whole pelvis radiotherapy, and concurrent chemotherapy were
      analyzed for toxicity. Median prescribed dose to the whole pelvis was 45 Gy (45
      50 Gy). Median prescribed dose to the paraaortic lymph nodes was 45 Gy (36-50).
      Thirty-five patients received cisplatin chemosensitization at a median dose of 40
      mg/m(2) (40-51), with a median of 5 cycles (2-6). RESULTS: Thirty-six patients
      were treated, 3 with positive paraaortic lymph nodes. The median follow-up
      interval was 32 months. Twenty-four patients (66.7%) had no evidence of disease
      at last follow-up. Thirteen patients (36.1%) had recurrence. Fifteen patients
      (41.7%) experienced acute grade 3 toxicity. CONCLUSION: Increased toxicity in
      patients warrants careful patient selection.

PMID- 19398096
TI  - Sour grapes: ultrasound abnormalities spurred delivery and neonatal surgery.

PMID- 19398097
TI  - Low-energy collision-activated dissociation electrospray ionization tandem mass
      spectrometric analysis of Sinorhizobial succinoglycan monomers.
AB  - Succinoglycan monomers (M1, M2, and M3) are octasaccharides with acetyl, pyruvyl,
      and/or succinyl groups as substituents derived from Sinorhizobium meliloti 1021.
      The dissociation patterns of the octasaccharides caused by low-energy collision
      activated dissociation (CAD) were investigated using triple quadrupole tandem
      mass spectrometry (MS) equipped with an electrospray ionization (ESI) source with
      increasing collision energy (CE) in negative ion mode. None of the succinoglycan
      monomers were fragmented at a CE of -25eV. When the CE was applied to -50 or 
      70eV, the loss of the terminal Gal residue and/or the succinyl group of the
      monomers was observed in the product ion scan mode. Interestingly, the acetyl and
      the pyruvyl groups in the succinoglycan monomers were not lost even when a CE of 
      70eV was applied, indicating that the substituents are more stable than the
      succinyl group in the octasaccharides.

PMID- 19398098
TI  - Effects of Lactobacillus plant arum on genes expression pattern in mice jejunal
      Peyer's patches.
AB  - Jejunal Peyer's patches contain specialized epithelial M cells that take up
      ingested microorganisms from the lumen of the gut by transcytosis. Using DNA
      micro array, we analyzed the gene expression patterns of jejunal Peyer's patches
      in order to gain insight into the molecular mechanism by which Lp6 interacted
      with the host organism in a gnotobiotic environment v. in the gut normal
      microflora. The micro array data revealed that, among approximately 14,000 genes,
      420 were expressed in Lp6 administration group at twofold or higher levels
      compared to the control group. These included genes involved in immune response,
      and cell differentiation, cell-cell signaling, cell adhesion, signal
      transcription, and transduction. Real-time PCR confirmed the reliability of the
      analysis. These data indicated that administration of Lactobacillus Lp6 was
      associated with a complex genetic response in the jejunal Peyer's patches.

PMID- 19398099
TI  - Speech errors reflect the phonotactic constraints in recently spoken syllables,
      but not in recently heard syllables.
AB  - Adults rapidly learn phonotactic constraints from brief production or perception
      experience. Three experiments asked whether this learning is modality-specific,
      occurring separately in production and perception, or whether perception
      transfers to production. Participant pairs took turns repeating syllables in
      which particular consonants were restricted to particular syllable positions.
      Speakers' errors reflected learning of the constraints present in the sequences
      they produced, regardless of whether their partner produced syllables with the
      same constraints, or opposing constraints. Although partial transfer could be
      induced (Experiment 3), simply hearing and encoding syllables produced by others
      did not affect speech production to the extent that error patterns were altered.
      Learning of new phonotactic constraints was predominantly restricted to the
      modality in which those constraints were experienced.

PMID- 19398100
TI  - Columnar organization in the motor cortex.

PMID- 19398101
TI  - Modeling and control of a pneumatically actuated inverted pendulum.
AB  - This paper presents the results of modeling of an inverted pendulum system driven
      by a linear pneumatic motor and equipped with relatively low-cost potentiometer
      based position measurement system. Based on the nonlinear model of the overall
      pendulum system, which also includes notable friction effects, a linearized model
      is derived. The linearized model is used as a basis for the design of state
      feedback controller based on LQ and LQG optimization procedures. The linear state
      feedback controllers are augmented by a compensator of nonlinear friction effects
      whose design is based on the results of experimental identification of an
      appropriate static friction model. The proposed pendulum controller structures
      have been verified by means of computer simulations and experimentally on the
      experimental setup of a pneumatically actuated inverted pendulum.

PMID- 19398102
TI  - Comprehensive two-dimensional liquid chromatography to quantify polyphenols in
      red wines.
AB  - A comprehensive two-dimensional liquid chromatography method has been applied for
      the quantification of polyphenols in red wines and compared to the most commonly
      employed conventional LC approach. Such methodology comprised the use of a
      microbore conventional HPLC column packed with totally porous particles in the
      first dimension and a partially porous column of conventional diameter in the
      second dimension. Even though a good number of applications in comprehensive LC
      have been reported, quantification experiments have been rarely described. To
      this regard, the advantages of comprehensive LC together with the employment of
      dedicated software capable of detecting and quantifying each peak from the 2D
      plot, have been taken into account for quantifying the most representative
      polyphenols in three different commercial Sicilian red wine samples. The
      optimized method has been validated in terms of linearity, sensitivity, detection
      and quantification limits. LODs as low as 0.02 ppm were obtained using the one
      dimensional HPLC-DAD method, whereas values lower than 0.10 ppm were obtained by
      comprehensive LC. However, comprehensive LC allowed the quantification of a
      higher number of compounds with RSD lower than 10% thanks to its improved
      resolving power. The separation capabilities of comprehensive LC allowed the
      analysis of complex natural samples without any pre-treatment to effectively
      reduce the interferences coming from the matrix.

PMID- 19398103
TI  - Functionalization of ceramic tile surface by sol-gel technique.
AB  - The aim of this investigation was the surface functionalization of industrial
      ceramic tiles by sol-gel technique to improve at the same time the cleanability
      of unglazed surfaces. This objective was pursued through the design and
      preparation of nanostructured coating that was deposited on polished unglazed
      tiles by air-brushing. In particular TiO(2)-SiO(2) binary film with 1, 2 or 5wt%
      of titania were prepared by using tetraethoxysilane and titania nanoparticles as
      precursors. The obtained films were characterized by scratch tests to verify the
      adhesion of the coatings to the polished tiles. To mainly evaluate the effect of
      the thermal treatment (temperature range 100-600 degrees C) on the
      photocatalicity of the coatings, the films were studied under UV exposure by
      contact angle measurements and cleanability test. Particular attention has been
      paid to preserve the aesthetical aspect of the final product and the obtained hue
      variation was evaluated by means of UV-visible spectroscopy and colorimetric
      analysis.

PMID- 19398104
TI  - PTFE/polyamide thin-film composite membranes using PTFE films modified with
      ethylene diamine polymer and interfacial polymerization: preparation and
      pervaporation application.
AB  - Plasma polymerization of ethylene diamine (EDA) on PTFE film surfaces is applied
      to modify PTFE surfaces to become hydrophilic and to incorporate amino groups
      onto PTFE surfaces. The surface-modified PTFE films are utilized as substrates
      for interfacial polymerization of EDA and trimesoyl chloride to prepare
      PTFE/polyamide thin-film composite (TFC) membranes. The effect of plasma power
      for plasma polymerization on the morphology and performances of the PTFE/PA TFC
      membranes are examined and discussed. The presence of amino groups on the PTFE
      substrates provides chemical linkages between PTFE and PA layers in interfacial
      polymerization to make the PTFE/PA TFC membranes are stable for pervaporation
      separations. A high permeation flux of 1910 g/hm(2) and a separation factor of
      290 are observed with the PTFE/PA TFC membranes for pervaporation dehydration on
      a 70 wt% isopropanol aqueous solution at 70 degrees C. This approach explores a
      new method to prepare PTFE-based TFC membranes via interfacial polymerizations.
      The prepared TFC membranes could be potentially utilized in pervaporation and
      nanofiltration separations.

PMID- 19398105
TI  - Synthesis of highly-monodisperse spherical titania particles with diameters in
      the submicron range.
AB  - Monodisperse titania spheres with particle diameters in the range 380-960 nm were
      successfully synthesized by hydrolysis and condensation of titanium
      tetraisopropoxide. The preparation was performed using ammonia or dodecylamine
      (DDA) as a catalyst in methanol/acetonitrile co-solvent at room temperature. The
      samples were characterized by powder X-ray diffraction, scanning electron
      microscopy, transmission electron microscopy, dynamic light scattering, and
      nitrogen sorption measurement. The use of DDA was effective for the synthesis of
      monodisperse titania spheres with low coefficient of variation. When the titania
      spherical particles with coefficient of variation less than 4% were obtained, the
      colloidal crystallization easily occurred simply by centrifugation. The
      monodispersity was maintained even after crystallization of the particles by high
      temperature annealing. The titania particles prepared using DDA had mesopores
      near the surface of the spheres, providing high pore accessibility to the sphere
      from the surface-air interface. The particle size uniformity and photocatalytic
      reactivity of the titania prepared using DDA were higher than those of the
      titania prepared using ammonia.

PMID- 19398106
TI  - Evaluating the hydrophilic-lipophilic nature of asphaltenic oils and naphthenic
      amphiphiles using microemulsion models.
AB  - Asphaltenes and naphthenic acid derivatives, which are polar and surface-active
      species, are known to interfere with the recovery of heavy crude oil by promoting
      the formation of stable emulsions. In this study, previously established
      microemulsion phase behavior models were applied to quantify the hydrophilic
      lipophilic nature of asphaltenic oils (bitumen, deasphalted bitumen, asphalt,
      naphthalene) and surface-active species found in heavy oils (naphthenic compounds
      and asphaltenes). For the test oils, the equivalent alkane carbon number (EACN)
      was determined by evaluating the "salinity shifts" of microemulsions formulated
      with a reference surfactant (sodium dihexyl sulfosuccinate--SDHS) and a reference
      oil (toluene) as a function of test oil volume fraction. Similarly, the
      characteristic curvature (C(C)) of surface-active species was determined by
      evaluating the salinity shifts as a function of the molar fraction of the surface
      active species in mixture with SDHS. As a part of the oil phase, asphaltenes and
      asphaltene-like species are highly hydrophilic, which lead to low EACN values
      despite their large molecular weight. As a surface-active material, asphaltenes
      are hydrophobic species that lead to the formation of water-in-oil emulsions.
      Naphthenates, particularly sodium naphthenates, are highly hydrophilic compounds
      that lead to the formation of oil-in-water emulsions. These hydrophilic
      lipophilic characterization parameters, and the methods used to determine them,
      can be used in the future to understand the phase behavior of complex oil-water
      systems.

PMID- 19398107
TI  - Lattice Boltzmann simulations of droplet formation during microchannel
      emulsification.
AB  - In this study, we compared microchannel droplet formation in a microfluidics
      device with a two phase lattice Boltzmann simulation. The droplet formation was
      found to be qualitatively described, with a slightly smaller droplet in the
      simulation. This was due to the finite thickness of the interface in the
      simulations. Dependence on dispersed flow rate could be very nicely predicted by
      the model, while a better insight was obtained on the internal pressures and flow
      velocities during droplet formation. These were found to be well described by
      simple relations; (1) the pressure inside the dispersed phase was predicted very
      well by the Laplace pressure while (2) the flow rate through the neck could be
      estimated by the flow through an orifice. These insights simplify the development
      of design rules for new microchannel devices.

PMID- 19398108
TI  - Physico-chemical investigation of nanostructures in liquid phases: nickel
      chloride ionic clusters confined in sodium bis(2-ethylhexyl) sulfosuccinate
      reverse micelles.
AB  - The confinement of finite amounts of nickel chloride in the hydrophilic core of
      sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse micelles dispersed in n
      heptane has been investigated by FT-IR, UV-vis-NIR and fluorescence
      spectroscopies. The analysis of experimental data consistently leads to
      hypothesize that NiCl(2) forms small size ionic clusters stabilized by a
      monolayer of oriented surfactant molecules. Due to confinement and interfacial
      effects, these ionic clusters show peculiar photophysical properties, which are
      different from those possessed by the bulk material. From NiCl(2)/AOT/n-heptane
      solutions, by evaporation of the organic solvent, interesting salt/surfactant
      nanocomposites at various salt concentrations have been prepared and
      characterised by WAXS. On the other hand, after mix with Na(2)S-containing dry
      micellar systems, the formation of NiS nanoparticles have been ascertained by UV
      vis spectroscopy.

PMID- 19398109
TI  - Temperature and pH-responsive properties of poly(styrene-co-maleic anhydride)
      grafting poly(oxypropylene)-amines.
AB  - A series of temperature- and pH-responsive copolymers were prepared by grafting
      poly(oxypropylene)-diamines (POP-amine) onto poly(styrene-co-maleic anhydride)
      (SMA) copolymers. Owing to the presence of poly(oxypropylene)-segments in the
      pendants and their expressive hydrogen bonding properties, the copolymers
      exhibited lower critical solution temperature (LCST) behavior in water with a
      range of 11-49 degrees C depending on the POP-segmental weight and the SMA
      backbone structure. Furthermore, the co-existence of -NH(2) termini in the
      pendants and amidoacids in the linking sites in the structures rendered the
      copolymers also responsive to environmental pH changes. Structural variations in
      the SMA backbones, particularly the ratio of styrene/maleic anhydride monomers,
      POP lengths, and amine functionalities largely influenced the copolymer
      aggregation in the medium with different pH or thermal conditions. The
      responsiveness was correlated to the surface morphologies observed by
      tapping/phase mode atomic force microscopy (TM-AFM) on Mica film surface and also
      fluorescent properties in aqueous solution.

PMID- 19398110
TI  - Numerical models for the evaluation of the contact angle from axisymmetric drop
      profiles: a statistical comparison.
AB  - Axisymmetric drop shape analysis (ADSA) is a well-established methodology for
      estimating the contact angle value and the surface tension of liquids starting
      from sessile drops images. It consists of an iterative procedure in which a best
      fit between a theoretical axisymmetric Laplacian curve and an experimental drop
      profile is performed. When only an evaluation of the geometric contact angle
      value is needed, a similar numerical approach can be adopted by using simpler
      algebraic models in place of a Laplace profile, thus allowing more
      straightforward implementations and shorter computation times. In this work the
      relative merits of the different methodologies are compared. Beside the standard
      ADSA procedure, four different mathematical models are examined, namely the
      circular and elliptical models, the first-order perturbative solution of the
      Laplace equation, and a cubic spline model. Their relative statistical
      performances are tested on both calculated and experimental drop profiles. For
      simulated drops, the actual capability of the models to predict the correct
      contact angle is also investigated.

PMID- 19398111
TI  - Room temperature fabrication of single crystal nanotubes of CaSn(OH)6 through
      sonochemical precipitation.
AB  - CaSn(OH)(6) nanotubes were fabricated by sonochemical precipitation method at
      room temperature. A direct rolling process from nanosheets to nanotubes was
      expected for the synthesis of CaSn(OH)(6) nanotubes. The transient CaSn(OH)(6)
      nanosheets are formed as intermediates produced by the spontaneous self-assembly
      and transformation of amorphous colloid clusters. During the crystallization
      process of intermediate nanosheets, the relaxation of surface strain in the
      nanosheet interfaces can induce the nanosheets to roll up to form nanotubes under
      ultrasonic conditions. In this synthesis, the addition of Na(2)CO(3) seems to
      play an important role in the formation, size, and shape control of the
      nanotubes. Investigations into the stability performance of the nanotubes
      indicate that the morphologies are very sensitive to pH and temperature. The
      method suggests a general strategy for the design and fabrication of functional
      single-crystalline nanotubes through an intermediate nanosheet rolling process.
      The in vitro fabrication of such single crystal nanotubes could shed light on
      fundamental mechanisms for closed hollow nanostructures. Furthermore, nanotubes
      produced in high yield and at low cost are envisioned to have applications in
      areas ranging from medicine to pharmaceuticals through to materials science.

PMID- 19398112
TI  - Dyslexia and dyscalculia: two learning disorders with different cognitive
      profiles.
AB  - This study tests the hypothesis that dyslexia and dyscalculia are associated with
      two largely independent cognitive deficits, namely a phonological deficit in the
      case of dyslexia and a deficit in the number module in the case of dyscalculia.
      In four groups of 8- to 10-year-olds (42 control, 21 dyslexic, 20 dyscalculic,
      and 26 dyslexic/dyscalculic), phonological awareness, phonological and visual
      spatial short-term and working memory, naming speed, and basic number processing
      skills were assessed. A phonological deficit was found for both dyslexic groups,
      irrespective of additional arithmetic deficits, but not for the dyscalculia-only
      group. In contrast, deficits in processing of symbolic and nonsymbolic magnitudes
      were observed in both groups of dyscalculic children, irrespective of additional
      reading difficulties, but not in the dyslexia-only group. Cognitive deficits in
      the comorbid dyslexia/dyscalculia group were additive; that is, they resulted
      from the combination of two learning disorders. These findings suggest that
      dyslexia and dyscalculia have separable cognitive profiles, namely a phonological
      deficit in the case of dyslexia and a deficient number module in the case of
      dyscalculia.

PMID- 19398113
TI  - The incidence of metabolic syndrome and its reversal in a cohort of schizophrenic
      patients followed for one year.
AB  - Cross-sectional studies showed a high prevalence of metabolic syndrome in
      patients with schizophrenia.This study aimed to identify the incidence of
      metabolic syndrome and its reversal in a non-preselected cohort of chronic
      psychotic patients in routine practice in one year follow-up and to find
      variables to describe development and reversal of metabolic syndrome. This cohort
      study was conducted as part of a disease management program and patients were
      included if they had two complete assessments in a one year follow-up. We
      conducted two logistic regressions to find variables to describe the development
      of metabolic syndrome and the reversal of metabolic syndrome. At the time of the
      first assessment 35% (n=92) of the 260 included patients had metabolic syndrome.
      Within one year 21 patients developed metabolic syndrome and 30 patients had it
      reversed. This was an incidence of 13% (21/168) and a reversal of 33% (30/92).
      Smoking, family history of cardiovascular diseases, and duration of disease >6
      years was associated with a higher risk of developing metabolic syndrome as well
      as abdominal obesity and dyslipidemia. Patients with abdominal obesity had a
      smaller chance of reversing metabolic syndrome. Other variables included in the
      logistic regression such as receiving cardiovascular/antidiabetic drug treatment
      or duration of disease >6 years did not alter the risk of reversing the metabolic
      syndrome. Our study showed that the natural course of metabolic syndrome is
      dynamic. A considerable number of patients developed or reversed the metabolic
      syndrome in one year follow-up.

PMID- 19398114
TI  - Impact of metabolic syndrome on distribution of cervicocephalic atherosclerosis:
      data from a diverse race-ethnic group.
AB  - BACKGROUND: Vascular localization of symptomatic large artery atherosclerotic
      (LAA) stroke differs for unknown reasons by race-ethnicity. The metabolic
      syndrome (MetSD) is associated with higher atherosclerotic stroke risk and
      comprises abnormal risk factors that can vary by race. Thus, we investigated
      whether MetSD may contribute to race-ethnic differences in LAA stroke by
      examining the association of MetSD with symptomatic intra- and extracranial
      atherosclerosis among a diverse race-ethnic group. METHOD: We analyzed data
      prospectively collected over a 4-year period on subjects with ischemic
      stroke/TIA. Independent vascular risk factor associations with intracranial and
      extracranial LAA vs. non-LAA mechanism were evaluated in two groups stratified by
      race-ethnicity; whites and non-whites (Hispanics, African-American, and Asian
      American). RESULTS: 1167 patients met study criteria. Intracranial LAA was more
      prevalent in non-whites vs. whites (20.4% vs. 9.6%, P<0.001), while extracranial
      LAA had a more frequent point value in whites compared to non-whites (10.7% vs.
      7.5%, P=0.267). The presence of MetSD was more prevalent in both intracranial and
      extracranial LAA group than in non-LAA group: no significant differences were
      observed in the prevalence of MetSD between intra vs. extracranial LAA or whites
      vs. non-whites. However, with increasing numbers of abnormal metabolic
      components, whites were more likely to have experienced extracranial LAA, whereas
      non-whites were more likely to have experienced intracranial LAA. After adjusting
      for covariates, MetSD was associated with extracranial LAA in whites (OR, 1.98;
      95% CI, 1.13-3.45), while there was a tendency that intracranial LAA was
      associated with MetSD in non-whites (OR, 1.80; 95% CI, 0.97-3.32). No association
      was found between MetSD and extracranial LAA in non-whites and between this
      syndrome with intracranial LAA in whites. CONCLUSIONS: Our results showed that
      the impact of MetSD on the distribution of cervicocephalic atherosclerosis
      differed by race-ethnicity. This finding may in part explain the well-known
      differences in race-ethnic predilection to intracranial or extracranial
      atherosclerosis.

PMID- 19398115
TI  - Association of plasma homocysteine concentration with cerebral white matter
      hyperintensity on magnetic resonance images in stroke patients.
AB  - BACKGROUND: Homocysteine (Hcy) has been recognized as a risk factor for
      atherosclerosis. White matter hyperintensity (WMH) on MRI has been regarded as a
      hallmark for cerebral small vascular disease. The study is to investigate the
      relationship between plasma Hcy level and WMH on a hospital-based cohort of
      Taiwanese stroke patients. METHODS AND RESULTS: A total of 352 consecutive stroke
      patients (64.7+/-11.2 years) were included. Severity of WMH was semi
      quantitatively evaluated with a scoring system. The top WMH score tertile was
      defined as severe white matter change (sv-WMH). Associations between Hcy tertile
      levels and sv-WMH were examined, adjusting for demographics and atherosclerosis
      risk factors. Subjects in the top Hcy tertile (>10.25 micromol/L) had higher WMH
      scores and prevalence of sv-WMH than those in the middle and in the bottom
      tertile. The adjusted odds ratio of having sv-WMH was 2.04 (95% confidence
      interval 1.20-3.47, p=0.008) for the top Hcy level tertile than for the lower two
      tertiles combined. CONCLUSION: Hcy is a risk factor for cerebral white matter
      lesion in stroke patients. Even mild hyperhomocysteinemia can significantly
      increase severity of cerebral microangiopathy.

PMID- 19398116
TI  - Evolution of aromatic prenyltransferases in the biosynthesis of indole
      derivatives.
AB  - A series of putative indole prenyltransferase genes could be identified in the
      genome sequences of different fungal strains including Aspergillus fumigatus and
      Neosartorya fischeri. The gene products show significant sequence similarities to
      dimethylallyltryptophan synthases from different fungi. We have cloned and
      overexpressed seven of these genes, fgaPT1, fgaPT2, ftmPT1, ftmPT2, 7-dmats,
      cdpNPT and anaPT in Escherichia coli and Saccharomyces cerevisiae. The
      overproduced enzymes were characterised biochemically. Three additional indole
      prenyltransferases, DmaW-Cs, TdiB and MaPT were also identified and characterised
      in the last years. Sequence analysis and comparison with known aromatic
      prenyltransferases as well as biochemical investigation revealed that these
      enzymes belong to a group of aromatic prenyltransferases. The characterised
      prenyltransferases are soluble proteins, catalyse different prenyl transfer
      reactions on indole moieties of various substrates and do not require divalent
      metal ions for their prenyl transfer reactions. In addition, indole
      prenyltransferases carry tryptophan aminopeptidase activity, which strengths
      their relationship in the evolution. These properties differ clearly from
      membrane-bound aromatic prenyltransferases from different sources and soluble
      prenyltransferases from bacteria. All of the indole prenyltransferases accepted
      only dimethylallyl diphosphate as prenyl donor. On the other hand, they showed
      broad substrate specificity towards their aromatic substrates. Diverse simple
      tryptophan derivatives and tryptophan-containing cyclic dipeptides were accepted
      by these enzymes, providing a strategy for convenient production of biologically
      active substances, e.g. by chemoenzymatic synthesis.

PMID- 19398117
TI  - The epithelial-mesenchymal transition induced by keratinocyte growth conditions
      is overcome by E6 and E7 from HPV16, but not HPV8 and HPV38: characterization of
      global transcription profiles.
AB  - The aim of this study was to evaluate the growth properties of primary human
      keratinocytes expressing E6 and E7 proteins, which are from either the beta- or
      alpha-genotypes, under different culture conditions. We demonstrated that
      keratinocytes expressing E6 and E7, from both HPV8 and 38, irreversibly underwent
      the epithelial-mesenchymal transition (EMT) when grown on plastic with FAD medium
      (F12/DMEM/5%FBS). Expression of E6/E7 from HPV16 was capable of fully overcoming
      the FAD-induced EMT. Immortalization was only observed in HPV16-transduced cell
      lines, while the more proliferating phenotype of both KerHPV8 and 38 was mainly
      related to FAD-induced EMT. Microarray analysis of exponentially growing cells
      identified 146 cellular genes that were differentially regulated in HPV16
      compared to HPV8- and 38-transduced cells. A large accumulation of transcripts
      associated with epidermal development and differentiation was observed in HPV16
      transduced cells, whereas transcripts of genes involved in the extracellular
      matrix, multicellular organismal processes, and inflammatory response were
      affected in HPV8 and 38-transduced cells.

PMID- 19398118
TI  - The comparative toxicity to soil invertebrates of natural chemicals and their
      synthetic analogues.
AB  - The introduction of Registration, Evaluation and Authorisation of Chemicals
      (REACH), requires companies to register and risk assess all substances produced
      or imported in volumes of >1 tonne per year. Extrapolation methods which use
      existing data for estimating the effects of chemicals are attractive to industry,
      and comparative data are therefore increasingly in demand. Data on natural toxic
      chemicals could be used for extrapolation methods such as read-across. To test
      this hypothesis, the toxicity of natural chemicals and their synthetic analogues
      were compared using standardised toxicity tests. Two chemical pairs: the
      napthoquinones, juglone (natural) and 1,4-naphthoquinone (synthetic); and
      anthraquinones, emodin (natural) and quinizarin (synthetic) were chosen, and
      their comparative effects on the survival and reproduction of collembolans,
      earthworms, enchytraeids and predatory mites were assessed. Differences in
      sensitivity between the species were observed with the predatory mite (Hypoaspis
      aculeifer) showing the least sensitivity. Within the chemical pairs, toxicity to
      lethal and sub-lethal endpoints was very similar for the four invertebrate
      species. The exception was earthworm reproduction, which showed differential
      sensitivity to the chemicals in both naphthoquinone and anthraquinone pairs.
      Differences in toxicity identified in the present study may be related to degree
      of exposure and/or subtle differences in the mode of toxic action for the
      chemicals and species tested. It may be possible to predict differences by
      identifying functional groups which infer increased or decreased toxicity in one
      or other chemical. The development of such techniques would enable the use of
      read-across from natural to synthetic chemicals for a wider group of compounds.

PMID- 19398119
TI  - Influence of experimental conditions on the formation of PCDD/Fs during the
      thermal reactions of 2,4,6-trichlorophenol.
AB  - In order to obtain information on thermochemical reactions of chlorophenols,
      which are well known as dioxin precursors, occurring during the combustion of
      municipal solid wastes, the combustion of 2,4,6-trichlorophenol (2,4,6-T(3)CP) in
      an air stream was investigated over a temperature range of 500-800 degrees C for
      a residence time of 1-20s using a quartz flow reactor. Gas chromatographic/mass
      spectrometric (GC/MS) analysis of the gaseous products and residues showed that
      2,4,6-T(3)CP began to decompose at 500 degrees C and produced several compounds,
      with 1,3,6,8- and 1,3,7,9-tetrachlorodibenzo-p-dioxins (T(4)CDD) as the major
      products. In addition, more than fifty organic products were observed in our
      experimental conditions. The yields of polychlorinated benzenes, phenols,
      dibenzofurans, and dibenzo-p-dioxins formed during the combustion of 2,4,6-T(3)CP
      were plotted as a function of temperature and residence time. Furthermore, it was
      found that the yields and the compositions of these gaseous products were
      strongly dependent on the residence time in the flow reactor.

PMID- 19398120
TI  - Combined scanning electron microscopy and image analysis to investigate airborne
      submicron particles: a comparison between personal samplers.
AB  - The main objectives of this study were: (i) to compare commonly used personal
      samplers and verify their collection efficiency with regards to submicron
      particles; (ii) to investigate how the submicron particles deposit onto the
      filter surface in order to assess the homogeneity of the deposition; (iii) to
      estimate the biases which could affect results when number concentration values
      have to be determined by particle counting. A method based on image analysis (IA)
      and scanning electron microscopy (SEM) is developed and adopted to investigate a
      large numbers of particles. Four different personal samplers were tested: the IOM
      sampler, the Button sampler and the German GSP for the inhalable aerosol
      fraction; the PEM sampler for the thoracic aerosol fraction. In order to
      investigate how particles distribute on the filters surface, the area of each
      filter was virtually divided into circular concentric areas or deposition zones
      (DZ). Results from different DZ of the same filter were compared. Uniformity of
      deposition was mostly observed for three of the four tested samplers. A
      significant radial distribution was observed only for the GSP sampler. The major
      homogeneity was found for the Button sampler. In order to estimate the relative
      collection efficiency between samplers, particles number concentrations
      determined by particle counting were compared. The GSP sampler provided the
      greatest concentrations but also the greatest variability. The PEM sampler
      provided the lowest concentrations. The homogeneity of particle deposition on the
      filter surface mostly affected results when counting is performed on localized
      areas of the filter.

PMID- 19398121
TI  - DDT and metabolites in fish from Lake Edward, Uganda.
AB  - This paper presents results based on determination of residue levels of 1,1,1
      trichloro-2,2-bis[p-chlorophenyl]ethane (DDT) and its metabolites in five fish
      species from Rwenshama landing site on Lake Edward, Uganda. The residue levels
      were analysed by using a GC-ECD and confirmed by GC-MS. The DDT residues detected
      in fish samples from Lake Edward were p,p'-DDT, o,p'-DDT, p,p'-DDE, o,p'-DDE,
      p,p'-DDD and o,p'-DDD. All the analysed samples of fish presented mean DDT
      residues ranging from non-detectable levels to 68 microg kg(-1) fresh weight.
      High levels of p,p'-DDT were detected in comparison to the metabolites (p,p'-DDE
      and p,p'-DDD). The detection of higher levels of p,p'-DDT than p,p'-DDE and p,p'
      DDD, in most fish samples, suggests recent exposure of fish to DDT. Generally,
      most of the fish samples had residue levels below the maximum residue limits
      (MRL) recommended by FAO/WHO Codex Alimentarius Commission.

PMID- 19398122
TI  - Finding environmental factors for respiratory diseases by nonparametric variable
      selection.
AB  - It is well known that the exposure to ambient air pollution might cause serious
      respiratory illnesses and that the weather conditions may also contribute to the
      seriousness. However, quantifying the effects of pollution and the weather
      condition is a difficult task due to the nonlinear nature of these impacts. The
      problem is further complicated by the possibly cumulative effects of these
      impacts. In this paper, the nonparametric additive (NPA) models, which have the
      advantage of ease in interpretation and forecasting, are employed for modeling
      the effects of pollution and weather. All models are derived by the local linear
      method. The variables in the final selected NPA model are chosen by cross
      validation method together with bootstrap test for the data of Hong Kong. For
      comparison the final selected linear regression (LR) model by the backward
      elimination method is also considered. It is found, interestingly, that the
      variables selected by nonparametric method and the usual backward elimination
      method for linear models are different. Furthermore, by comparing forecasted
      values obtained from the NPA and LR models and true values the final selected NPA
      model is shown to outperform the LR model.

PMID- 19398123
TI  - Murine strain differences in hemostasis and thrombosis and tissue factor pathway
      inhibitor.
AB  - INTRODUCTION: Differences among murine strains often lead to differential
      responses in models of human disease. The aim of the current study was to
      investigate whether differences exist among strains in models of hemostasis and
      thrombosis and whether these differences are reflected in differences in the
      tissue factor (TF) pathway. METHODS: We examined baseline hemostatic parameters
      and the response to FeCl3-induced arterial thrombosis and a tail vein bleeding
      model in C57BL/6J (C57), 129S1/SvImJ (129S), and Balb/cJ (BalbC) mice. Finally,
      we examined TF and tissue factor pathway inhibitor (TFPI) activities in blood and
      expression in vascular tissue to determine whether these factors covary with a
      thrombotic phenotype. RESULTS: No differences were observed in PT or aPTT among
      strains. 129S mice had lower platelet counts (p<0.001). BalbC had an increased
      rate of occlusion (mean occlusion time of 330+/-45 sec) in a FeCl(3)-induced
      model of thrombosis when compared to C57 (1182+/-349 sec) or 129 S (1442+/-281
      sec) (p<0.05). Similarly, BalbC demonstrated reduced blood loss in tail bleeding
      experiments when compared to C57 and 129S. Vascular expression of TF and TFPI
      content did not correlate with the thrombotic phenotype of BalbC. However,
      circulating TFPI activities were lower in BalbC compared to both C57 and 129S
      mice. When normalized to circulating TF activities, BalbC had lower circulating
      TFPI activity than C57 and 129S, and there was a significant correlation between
      tail bleeding and normalized TFPI activity (r=0.67). CONCLUSIONS: These data
      suggest that there are significant differences among strains in thrombosis and
      hemostasis and that circulating TFPI activity correlates with these differences.

PMID- 19398124
TI  - Intraperitoneal access via direct puncture is an alternative way to deliver
      intraperitoneal chemotherapy in ovarian, fallopian tube and primary peritoneal
      cancer.
AB  - OBJECTIVES: Intraperitoneal (IP) chemotherapy has not been widely accepted in the
      treatment of ovarian cancer. One of the main reasons is the lack of a convenient
      and safe way to deliver IP therapy. The objective of this study was to
      investigate the feasibility of delivering IP chemotherapy via direct puncture
      using a peripheral venous needle, as well as evaluating the associated risk
      factors and complications in the primary treatment of ovarian, fallopian tube,
      and primary peritoneal cancer. METHODS: The clinical records of all patients with
      stage II-IV epithelial ovarian, fallopian tube, and primary peritoneal cancer at
      Sun Yat-sen University Cancer Center from 01/1995 to 11/2006 were reviewed
      retrospectively to identify patients who had received IP therapy via direct
      puncture after primary cytoreduction. RESULTS: We identified 194 patients, and
      121 (62.4%) of them successfully completed six or more cycles of IP chemotherapy,
      whereas 73 (37.6%) failed. Two (1%) patients ceased IP therapy directly due to IP
      access related complications and 35 (18.1%) discontinued IP therapy for reasons
      unrelated to IP access. Old age might be a potential risk factor for IP therapy
      failure. The IP therapy failure rate in patients over 60 years old was higher
      than that in patients under or at 60 (57.1% versus 34.3%, P=0.021). Body mass
      index were not associated with IP therapy failure. CONCLUSIONS: IP access via
      direct puncture using a peripheral venous needle could be an alternative and safe
      way to deliver IP chemotherapy in the primary treatment of ovarian cancer.

PMID- 19398126
TI  - Radical hysterectomy for FIGO stage IIB cervical cancer: clinicopathological
      characteristics and prognostic evaluation.
AB  - OBJECTIVE: To clarify the clinicopathological features and prognostic factors of
      patients with FIGO stage IIB cervical cancer who were treated with radical
      hysterectomy. METHODS: One hundred thirty-nine FIGO stage IIB patients with
      squamous or adenosquamous cell carcinoma (median age, 51 years) who were treated
      with primary radical hysterectomy were examined retrospectively. Sixty-six FIGO
      stage IIB patients who were treated with primary radiotherapy (median age, 70
      years) were included for comparison of survival. RESULTS: Fifty percent (70/139)
      of the patients had pathological parametrial involvement. Among them, the
      positive rate of pelvic lymph nodes was 71% (50/70). Ninety-nine percent
      (138/139) of the tumors were completely removed, and the pelvic control rate was
      88%. Major complications requiring surgery were found in 2.9% (4/139).
      Significant differences in survival were found among patients in subgroups
      according to pathological parametrial involvement, pelvic lymph node status,
      tumor size, lymph-vascular space invasion, and depth of myometrial invasion (log
      rank test, P<0.05). Of these, the Cox proportional-hazard model revealed that
      parametrial involvement (P=0.001, 95% CI 1.992-6.297) and lymph node metastasis
      (P=0.042, 95% CI 1.023-3.298) were independent prognostic factors. The 5-year
      survival rate and relapse-free survival at 36 months were 69% and 72% among the
      radical hysterectomy group, and 69% and 75% among the radiotherapy group. The Cox
      model adjusted for age showed no significant differences in survival and relapse
      free survival between these two groups. CONCLUSION: Pathological parametrial
      involvement and positive nodes were prognostic factors for surgically treated
      patients with FIGO stage IIB cervical cancer.

PMID- 19398127
TI  - Residual tumor after neoadjuvant chemotherapy and interval debulking surgery for
      advanced endometrial cancer.

PMID- 19398128
TI  - p53 autoantibodies, cytokine levels and ovarian carcinogenesis.
AB  - OBJECTIVE: To address the hypothesis that type II ovarian carcinoma, mutation of
      p53 and plasma levels of particular cytokines are associated with the generation
      of p53-specific serum autoantibody (AAb) responses in patients. METHODS: Levels
      of CA125, 17 cytokines and AAbs to tumor-associated antigens including p53 were
      measured in plasma of 130 gynecologic tumor patients and 84 healthy controls.
      TP53 exons 4-9 were sequenced in tumor specimens. RESULTS: p53 AAbs are
      associated with high grade, but not low grade ovarian carcinoma. Seropositivity
      for p53 AAb occurred only in those ovarian carcinoma patients whose tumors
      contained mutated TP53, regardless of the exon targeted. Higher p53 AAb levels
      were detected in ovarian carcinoma patients who had higher stage disease, but p53
      AAb levels were not correlated with CA125 levels. Among high-grade carcinoma
      patients, there was no relationship between p53 AAb seropositivity and
      seropositivity to other tumor-associated antigens tested, CA125 level or survival
      outcome. Both high and low grade ovarian carcinoma patients exhibited elevated
      levels of IL6, IL8 and IL10 as compared to healthy volunteers, although increased
      levels of IL5, MCP1, MIP1 and TNFalpha were associated only with high grade and
      advanced disease. Higher levels of p53AAb responses were correlated with elevated
      circulating IL4 and IL12, but reduced IL8 levels. CONCLUSION: Type II, but not
      type I, ovarian carcinoma patients had elevated serum levels of p53 AAb. P53 AAb
      is associated with mutation of TP53, higher plasma IL4 and IL12 but lower plasma
      IL8 levels and no survival advantage.

PMID- 19398129
TI  - Acute lymphoblastic leukemia following severe congenital neutropenia or de novo
      ALL?
AB  - Acute lymphoblastic leukemia (ALL) presenting with neutropenia alone is very
      rare. We describe a newborn with an early life-threatening infection, severe
      neutropenia and bone marrow findings compatible with severe congenital
      neutropenia (SCN). She was treated with granulocyte colony-stimulating factor (G
      CSF) with complete neutrophil recovery. Three months later she developed a pro-B
      ALL. We identified a rare loss of 5'-MLL present at the diagnosis of SCN and ALL
      by FISH analysis using two different MLL (11q23) probes. Molecular analyses for
      SCN causing mutations (ELA-2, HAX-1 and G6PC3) and for somatic mutations of the
      CSF3R gene were negative. The early presence of 5'-MLL loss in bone marrow
      samples may favor the diagnosis of de novo ALL. Nevertheless, the genetic
      background for SCN is heterogeneous and a non-described mutation for SCN followed
      by a secondary ALL cannot be excluded. Further genetic investigation may be
      useful to gain insight into this rare condition in children.

PMID- 19398130
TI  - Characterization of decidual leukocyte populations in cynomolgus and vervet
      monkeys.
AB  - The objective of this study was the phenotypic and functional evaluation of
      decidual immune cells in the cynomolgus and vervet monkeys. Early pregnancy (days
      36-42) deciduas were obtained by fetectomy for histological evaluation and
      decidual mononuclear leukocyte (MNL) isolation. While peripheral NK (pNK) cells
      in these species do not express CD56, CD56(+) NK cells were abundant in decidual
      samples. The majority of decidual NK (dNK) cells (>80%) had high light-scatter
      characteristics and were CD56(bright)CD16(+) cells with no or very low levels of
      natural cytotoxicity receptors (NKp46, NKp30) and NKG2A, while a minor population
      were small CD56(dim)CD16(-) lymphocytes also expressing less NKp46, NKp30 and
      NKG2A than pNK cells. All dNK cells were found to be perforin(+); however, their
      cytotoxic potential was low and cynomolgus dNK cells showed strongly reduced
      cytotoxicity against target cells compared with pNK cells. Macrophages and T
      cells together comprised approximately 25-30% of decidual MNL. Decidual T cells
      contained a higher proportion of the minor T cell subtypes (gammadeltaT cells,
      CD56(+) T cells) compared with peripheral blood. A subset of DC-SIGN(+)
      macrophages, with a distribution adjacent to areas of placental attachment in
      contrast to the widespread setting of general CD68(+) cells, was identified in
      both species. Together, these results demonstrate that the maternal-fetal
      interface in both cynomolgus and vervet monkeys is very rich in immune cells that
      have similar phenotypes to those seen in humans, indicating that both species are
      excellent models to study the contributions of distinct immune cell populations
      to pregnancy support.

PMID- 19398131
TI  - Chronic propranolol treatment affects expression of adrenoceptors on peritoneal
      macrophages and their ability to produce hydrogen peroxide and nitric oxide.
AB  - Using both immunocytochemical and flow cytometric analyses of rat peritoneal
      exudate cells constitutive expression of tyrosine hydroxylase and both beta(2)-
      and alpha(1)- adrenoceptors on macrophages was revealed. Furthermore, according
      to the characteristic assemblage of tyrosine hydroxylase and adrenoceptor subtype
      expression different macrophage subsets were identified. In vitro treatment of
      macrophages with the non-selective alpha,beta-adrenoceptor agonist arterenol
      and/or the beta-adrenoceptor antagonist propranolol indicated that beta
      adrenoceptors potentiated nitric oxide (NO) production and suggested alpha
      adrenoceptor-mediated suppression of hydrogen peroxide (H(2)O(2)) production. An
      increase in H(2)O(2) production in the presence of the alpha(1)-adrenoceptor
      antagonist ebrantil provided support for this. Chronic propranolol treatment in
      vivo led to increased NO and H(2)O(2) production by peritoneal macrophages.
      Furthermore, this treatment resulted in opposing effects on the expression of
      beta(2)- and alpha(1)-adrenoceptors on peritoneal macrophages (a stimulatory
      effect on beta(2)-adrenoceptors and a suppressive effect on alpha(1)
      adrenoceptors). In conclusion, a subset of resident peritoneal macrophages
      synthesizes catecholamines, which may exert differential effects on H(2)O(2) and
      NO production via distinct adrenoceptors. Finally, chronic propranolol treatment
      affected adrenoceptor expression on peritoneal macrophages and altered their
      capacity to generate NO and H(2)O(2).

PMID- 19398133
TI  - The associations of gender, depression and elder mistreatment in a community
      dwelling Chinese population: the modifying effect of social support.
AB  - The aims of this study are to: (1) examine the gender differences in the
      association of depression and elder mistreatment (EM) in a community-dwelling
      Chinese population; and (2) examine the potential differential modifying effect
      of greater social support on these associations. We conducted a cross-sectional
      study of 141 women and 270 men aged 60 years or greater who presented to an urban
      medical center. EM was assessed using the modified Vulnerability to Abuse
      Screening Scale (VASS) and depression was assessed using the Geriatric Depression
      Scale (GDS) and overall social support was measured using the Social Support
      Index (SSI). After adjusting for potential confounders, depression was associated
      with 447% increased risk for EM among men (odds ratio, OR = 4.47; 95% confidence
      intervals (CI) = 1.52-13.13) and 854% increased risk for EM among women (OR =
      8.54; 95% CI = 2.85-25.57). After examining the effect of greater social support
      on depression (social support x depression), depression was no longer associated
      with increased risk for EM in men (parameter estimate = PE = 0.62 + or - 0.82 (+
      or - S.E.M.) = 0.82, p = 0.454). However, among women, depression remained as a
      significant risk factor for EM (PE = 1.49 + or - 0.68, p = 0.029). Depression is
      significant risk factor for EM for both men and women. However, effect of greater
      overall social support may have higher protective effect in men than in women.

PMID- 19398132
TI  - Common astrocytic programs during brain development, injury and cancer.
AB  - In addition to radial glial cells of neurohistogenesis, immature astrocytes with
      stem-cell-like properties cordon off emerging functional patterns in the
      developing brain. Astrocytes also can be stem cells during adult neurogenesis,
      and a proposed potency of injury-associated reactive astrocytes has recently been
      substantiated. Astrocytic cells might additionally be involved in cancer stem
      cell-associated gliomagenesis. Thus, there are distinguishing roles for stem-cell
      like astrocytes during brain development, in neurogenic niches in the adult,
      during attempted reactive neurogenesis after brain injury or disease and during
      brain tumorigenesis.

PMID- 19398134
TI  - The short-term effect of acetylcholinesterase inhibitor on the regional cerebral
      blood flow of Alzheimer's disease.
AB  - This study is to investigate changes in regional cerebral blood flow (rCBF) of
      Alzheimer's disease (AD) in short-term treatment with acetylcholinesterase
      inhibitor (ChEI). rCBF was measured by single photon emission computed tomography
      (SPECT). CBF measurements were performed in 13 AD patients before treatment and 4
      months later, while the control group with syncope or headache consisted of 17
      patients. The clinical diagnosis of AD was based on the NINCDS-ADRDA criteria.
      Significant increases in rCBF were noted in the left angular, the right superior
      frontal gyrus, the right occipital, the left temporal lobe and the left orbital
      gyrus at the end of short-term therapy. Reduction in the rCBF before treatment is
      more profound in the left superior temporal, the right precentral and the both
      inferior frontal gyri compared with the control group. It achieved increase of
      rCBF after ChEI treatment. Also it overall increased in global cognitive
      functions including Korean Version Mini Mental State Examination (K-MMSE) and
      Clinical Dementia Rating (CDR). Treatment with ChEI for 4 months could increase
      rCBF and improve cognitive function of patients with AD.

PMID- 19398135
TI  - The impact of chronic diseases on the health and well-being of South Africans in
      early and later old age.
AB  - This paper examines the impact of chronic disease status on health and well-being
      of South Africans in early and later old age. A structured questionnaire,
      comprising demographic characteristics, self-reported chronic disease status, an
      18-item health problems scale and the health and well-being sub-scales from the
      SF-12 was used to collect data from 400 black, 101 Indian, 107 white and 102
      colored residents of Greater Pretoria, South Africa. One hundred and ninety (27%)
      reported no chronic disease, 181 (25%) had hypertension alone, 179 (25%) had
      hypertension combined with one or more other chronic diseases and 160 (23%) had
      other chronic diseases without hypertension. There were no significant
      differences on health and well-being by race, language, gender or marital status.
      However, there were significant race, age group and gender effects on chronic
      disease status. Controlling for these factors, the no chronic disease group had
      significantly better health and well-being than the other three groups; the group
      with hypertension alone also had better health and well-being than the chronic
      disease groups with and without hypertension. It was concluded that chronic
      diseases combined with and without hypertension were more detrimental to health
      and well-being than no chronic disease or hypertension alone.

PMID- 19398136
TI  - The effect of functional balance training in frail nursing home residents.
AB  - The purpose of this study was to design and evaluate the specifically targeted
      functional balance training for a group of frail nursing home residents. Fifty
      residents of two nursing homes were assigned to an exercise and control group.
      Thirty-three participants (age 75.7 + or - 6.7 years) in the balance training
      group finished 12 weeks of training protocol that consisted of 14 activities that
      challenged different balance subsystems. The results showed that the participants
      in the training group reached higher score on Berg Balance Scale (BBS) (p <
      0.001), were able to stand longer on a compliant surface with eyes opened and
      closed (p < 0.01 and p < 0.02, respectively), and were faster at both, the four
      square and ten meter walk tests (p < 0.001), whereas there were no changes for
      the control group during the same time period. Anyhow, functional improvement of
      balance did not reflect in the parameters of postural sway. In conclusion our
      results suggest that the specifically targeted functional balance training is
      effective as far as functional activities are concerned while this kind of
      training does not reflect as a change in the steadiness of the center of pressure
      (CoP).

PMID- 19398137
TI  - Obesity and cardiovascular disease: from pathophysiology to risk stratification.
AB  - Obesity is associated with numerous co-morbidities such as cardiovascular
      diseases (CVD), type 2 diabetes, hypertension and others. As obesity is
      considered to be a major risk factor for atherosclerosis, understanding of the
      underlying mechanisms leading to obesity and linking obesity with atherogenesis
      is necessary, for the development of therapeutic strategies against
      atherosclerosis. The pathophysiology of CVD linked to obesity is an area of
      intensive research. In this review we examine the role of obesity on CVD, and we
      focus on specific mechanisms of major importance in atherogenesis, such as the
      role of adipokines, insulin resistance, endothelial function and cardiac
      structure with emphasis on the effects of obesity on vascular endothelium and
      atherosclerosis. We then proceed from the pathophysiology of obesity to clinical
      practice, and we discuss clinical studies linking obesity with subclinical or
      overt CVD. We highlight that obesity is an easily assessed cardiovascular risk
      factor in the clinical setting and strategies to promote optimal body weight
      should be encouraged.

PMID- 19398138
TI  - Different subpopulations of endothelial progenitor cells and circulating
      apoptotic progenitor cells in patients with vascular disease and diabetes.
AB  - AIMS: Endothelial progenitor cells (EPCs) represent a repair mechanism involving
      reendothelialization and neoangiogenesis. Patients with both diabetes and known
      vascular disease have low numbers of circulating EPCs. To assess the role of
      diabetes in vascular disease we investigated the number and viability of
      circulating EPCs and related this to endothelial function. METHODS: Different EPC
      subpopulations were enumerated by flow cytometry using triple staining (CD34,
      CD133, KDR). Viability was assessed by 7AAD and Annexin-V-staining. Endothelial
      function was evaluated by Endo-PAT2000 in 19 patients with known vascular disease
      without diabetes and 20 patients with vascular disease and diabetes mellitus.
      RESULTS: CD34+, CD133+, CD34+/CD133+, CD34+/KDR+, CD34+/CD133+/KDR+ cell counts
      did not differ between patients with and without diabetes. CD34-/CD133+/KDR+
      cells were lower, whereas staining for apoptosis in progenitor cells was higher
      in patients with diabetes. Progenitor cell counts did not correlate to peripheral
      arterial function test. DISCUSSION: Patients having diabetes and vascular disease
      have lower CD34-/CD133+/KDR+ EPC counts, a recently discovered subpopulation of
      EPCs, and larger proportion of apoptotic EPCs. Higher apoptotic rates of
      progenitor cells in diabetes could represent an important mechanism explaining
      lower functional capability of these cells. These observations may be of
      importance for the complications associated with diabetes mellitus.

PMID- 19398139
TI  - The effects of drug-eluting stent polymer on measurement of strut thickness by
      optical coherence tomography: in-vitro comparison with bare-metal stent.
AB  - BACKGROUND: Although measurement of stent strut by optical coherence tomography
      (OCT) is important as an index for evaluating incomplete stent apposition, the
      effects of drug-eluting stents (DES) polymer on it are unknown. METHODS AND
      RESULTS: DES and bare-metal stents (BMS) as platforms of DES were implanted in an
      artificial artery. Thickness of stent strut, defined as a distance from inner
      surface of the strut to the adjacent surface of the tube, and thickness of high
      signal band were measured by OCT. Each measurement of DES was significantly
      larger comparing with BMS. CONCLUSION: This in-vitro study demonstrates that DES
      polymer may influence OCT measurement for the stent strut.

PMID- 19398141
TI  - Usefulness of brachial-ankle pulse wave velocity as a predictive marker of
      multiple coronary artery occlusive disease in Korean type 2 diabetes patients.
AB  - Multiple coronary artery occlusive disease (multiple CAOD) is the most fatal and
      frequently observed coronary artery disease in type 2 diabetes patients, but no
      simple, non-invasive screening tool is available yet. The aim of this study is to
      evaluate the arterial stiffness in type 2 diabetes patients using brachial-ankle
      pulse wave velocity (baPWV), to demonstrate the correlation between arterial
      stiffness and multiple CAOD, and to suggest the cutoff point of baPWV for
      predicting multiple CAOD in Korean type 2 diabetes patients. One hundred and
      eighty-one diabetes and 262 non-diabetes patients were enrolled in the study.
      Routine anthropometric and serologic data were collected. baPWV was measured the
      day before coronary angiography, and the severity of CAOD was assessed with
      Gensini score after angiography. baPWV and Gensini score were significantly
      increased in diabetes patients and Gensini score had a positive correlation with
      baPWV. Subjects in the highest tertile of baPWV showed odds ratio of 3.06 for
      multiple CAOD compared to the lowest tertile. In ROC curve, baPWV at 1635 cm/s
      showed 73% sensitivity and 75% specificity with AUC 0.76 in diabetes patients in
      detecting multiple CAOD. Therefore, baPWV may be utilized a screening tool for
      predicting multiple CAOD, especially in type 2 diabetes patients.

PMID- 19398140
TI  - High-throughput cellular microarray platforms: applications in drug discovery,
      toxicology and stem cell research.
AB  - Cellular microarrays are powerful experimental tools for high-throughput
      screening of large numbers of test samples. Miniaturization increases assay
      throughput while reducing reagent consumption and the number of cells required,
      making these systems attractive for a wide range of assays in drug discovery,
      toxicology, stem cell research and potentially therapy. Here, we provide an
      overview of the emerging technologies that can be used to generate cellular
      microarrays, and we highlight recent significant advances in the field. This
      emerging and multidisciplinary approach offers new opportunities for the design
      and control of stem cells in tissue engineering and cellular therapies and
      promises to expedite drug discovery in the biotechnology and pharmaceutical
      industries.

PMID- 19398142
TI  - Does the workplace-smoking ban eliminate differences in risk for environmental
      tobacco smoke exposure at work?
AB  - OBJECTIVES: A workplace-smoking ban in the Netherlands was introduced on January
      1, 2004. Before the ban male and low educated employees were at higher risk for
      exposure to environmental tobacco smoke (ETS). Effective implementation of the
      ban should result not only in an overall decline of exposure, but also in the
      disappearance of systematic differences in exposure between subgroups of
      employees. METHODS: Data from a Dutch continuous Internet survey were used. From
      July 2003 through June 2005, 200 respondents were randomly selected each week.
      The sample consisted of 11,291 non-smoking, working respondents, aged 16-65
      years. RESULTS: ETS exposure decreased among all employees and among subgroups at
      higher risk before the ban. However, also after the ban, males and low educated
      employees were still most likely to be exposed to ETS. CONCLUSIONS: The workplace
      smoking ban was effective in reducing ETS exposure among employees. However,
      after the ban still 52.2% of non-smoking workers reported to be exposed. We did
      not find the expected stronger effect among employees who were at higher risk.
      Both before and after implementation of the ban, males and lower educated
      employees were about two times more likely to be exposed to ETS.

PMID- 19398143
TI  - Evolution education in natural history museums.

PMID- 19398144
TI  - The significance of reflectance confocal microscopy in the assessment of solitary
      pink skin lesions.
AB  - BACKGROUND: Solitary pink lesions often manifest nondescript clinical and
      dermatoscopic primary morphologic features. The differential diagnosis for pink
      lesions tends, therefore, to be broad, ranging from inflammatory processes to
      malignancy. In vivo reflectance confocal microscopy (RCM) may help in the
      evaluation of pink lesions. OBJECTIVE: We sought to demonstrate the use of RCM as
      an adjunct to the bedside diagnosis of pink lesions. METHODS: We describe a
      series of patients with clinically and dermatoscopically equivocal pink lesions
      for which RCM examination allowed for a rapid and accurate diagnosis. All lesions
      were excised for histopathologic evaluation. Integrating the findings in the case
      series with a literature review, we present RCM diagnostic criteria for pink
      lesions. RESULTS: Lesions included basal cell carcinoma, squamous cell carcinoma,
      amelanotic melanoma, and inflamed seborrheic keratosis. RCM shows distinctive
      findings for each diagnostic entity when stratified by anatomic level into
      suprabasal epidermis, dermoepidermal junction, and papillary dermis. In the cases
      presented RCM allowed for a rapid and accurate noninvasive diagnosis.
      LIMITATIONS: The study is descriptive and does not test accuracy of RCM criteria
      in a prospective series of pink lesions. CONCLUSION: RCM may add useful
      diagnostic features to the clinical evaluation of solitary pink lesions.

PMID- 19398146
TI  - Synthesis and anti-tumor activities of some new pyridines and pyrazolo[1,5
      a]pyrimidines.
AB  - Cyclocondensation of cyanoacetamide, cyanothioacetamide and 3-aminopyrazols with
      sodium salt of 3-hydroxy-1-(2-naphthyl)prop-2-en-1-one gives pyridin-2-one,
      pyridin-2(1H)-thione, and pyrazolo[1,5-a]pyrimidine derivatives. These
      derivatives showed potent anti-tumor cytotoxic activity in vitro using different
      human cancer cell lines.

PMID- 19398145
TI  - Quality of life in the actinic neoplasia syndrome: The VA Topical Tretinoin
      Chemoprevention (VATTC) Trial.
AB  - BACKGROUND: Keratinocyte carcinomas (KCs) are the most common malignancies of the
      skin. As lesions have a low mortality rate, understanding quality-of-life (QoL)
      factors is necessary in their management. OBJECTIVE: To assess QoL and associated
      patient characteristics in those with a history of keratinocyte carcinomas.
      METHODS: We conducted a cross-sectional study of veterans with a history of KCs
      enrolled in a randomized controlled trial for chemoprevention of keratinocyte
      carcinomas. Study dermatologists counted actinic keratoses (AKs) and assessed for
      skin photodamage. QoL was assessed using Skindex-29 and KC-specific questions.
      Demographics were self-reported. RESULTS: Participants (n = 931) enrolled at 5
      clinical sites had worse QoL on all subscales (emotions, functioning, and
      symptoms) compared to a reference group of patients without skin disease.
      Univariate analysis demonstrated worse QoL associated with higher AK count, past
      5-fluorouracil (5-FU) use, and greater sun sensitivity. Multivariate analysis
      demonstrated that higher AK count and past 5-FU use were independently related to
      diminished QoL. Higher comorbidities showed modest associations on the symptoms
      and functioning subscales. Number of previous KCs was not independently
      associated with any QoL differences. LIMITATIONS: Study population may not be
      generalizable to the general population. Counting of AKs is of limited
      reliability. Previous 5-FU use is self reported. CONCLUSIONS: A history of ever
      use of 5-FU and present AKs was strongly associated with worse QoL. We find it
      more useful to consider these patients as having the chronic condition "actinic
      neoplasia syndrome," whose burden may be best measured by factors other than
      their history of KCs.

PMID- 19398147
TI  - Structural and functional responses of benthic invertebrates to imidacloprid in
      outdoor stream mesocosms.
AB  - Structural and functional responses of a benthic macroinvertebrate assemblage to
      pulses of the insecticide imidacloprid were assessed in outdoor stream mesocosms.
      Imidacloprid pulses reduced invertebrate abundance and community diversity in
      imidacloprid-dosed streams compared to control streams. These results correlated
      well with effects of imidacloprid on leaf litter decomposition and feeding rates
      of Pteronarcys comstocki, a stonefly, in artificial streams. Reductions in oxygen
      consumption of stoneflies exposed to imidacloprid were also observed in
      laboratory experiments. Our findings suggest that leaf litter degradation and
      single species responses can be sensitive ecotoxicological endpoints that can be
      used as early warning indicators and biomonitoring tools for pesticide
      contamination. The data generated illustrates the value of mesocosm experiments
      in environmental assessment and how the consideration of functional and
      structural endpoints of natural communities together with in situ single species
      bioassays can improve the evaluation and prediction of pesticide effects on
      stream ecosystems.

PMID- 19398148
TI  - Musical and verbal memory in Alzheimer's disease: a study of long-term and short
      term memory.
AB  - Musical memory was tested in Alzheimer patients and in healthy older adults using
      long-term and short-term memory tasks. Long-term memory (LTM) was tested with a
      recognition procedure using unfamiliar melodies. Short-term memory (STM) was
      evaluated with same/different judgment tasks on short series of notes. Musical
      memory was compared to verbal memory using a task that used pseudowords (LTM) or
      syllables (STM). Results indicated impaired musical memory in AD patients
      relative to healthy controls. The deficit was found for both long-term and short
      term memory. Furthermore, it was of the same magnitude for both musical and
      verbal domains whether tested with short-term or long-term memory tasks. No
      correlation was found between musical and verbal LTM. However, there was a
      significant correlation between verbal and musical STM in AD participants and
      healthy older adults, which suggests that the two domains may share common
      mechanisms.

PMID- 19398149
TI  - Myricetin sensitizes malignant glioma cells to TRAIL-mediated apoptosis by down
      regulation of the short isoform of FLIP and bcl-2.
AB  - The flavonoid Myricetin has been reported to exhibit therapeutic activity in
      cancer. In this study glioblastoma cells and human astrocytes were treated with
      Myricetin, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) or
      the combination of both. Treatment with subtoxic doses of Myricetin in
      combination with TRAIL induces rapid apoptosis in glioma cells. Notably, human
      astrocytes were not affected by the combined treatment consisting of Myricetin
      and TRAIL. Combined treatment with Myricetin and TRAIL augmented the activation
      of initiator caspases-8/-9 and effector caspases-3/-7. Furthermore, Myricetin
      down regulated the expression of the long and short isoform of c-FLIP and bcl-2
      and over-expression of the short isoform of c-FLIP (S) and bcl-2 attenuated
      apoptosis induced by the combination of Myricetin and TRAIL. Furthermore,
      Myricetin did not modulate the mRNA levels of c-FLIP, suggesting that Myricetin
      modulates the expression of c-FLIP in a posttranscriptional manner. In summary,
      the short isoform of c-FLIP and bcl-2 are key regulators in TRAIL-Myricetin
      mediated cell death in malignant glioma.

PMID- 19398150
TI  - Src inhibitor dasatinib inhibits growth of breast cancer cells by modulating EGFR
      signaling.
AB  - EGF-receptor family members (EGFRs) as well as c-Src are over expressed in
      approximately 70% of breast cancer, and in most of the tumors c-Src is co-over
      expressed with at least one of the EGFRs, suggesting that they may interact
      functionally and play a role in the development and progression of the
      malignancy. We hypothesize that a small molecule inhibitor of c-Src dasatinib
      (BMS-354825; Bristol Myers Squibb), exerts its effects on breast cancer cells by
      modulating EGFR signaling. Indeed, we found that dasatinib causes inhibition of
      breast cancer cells overexpressing EGFR, HER-2 and HER-3 (MDA-MB-468, SKBR3, MDA
      MB-453, and MDA-MB-231) in a dose and time-dependent manner. Dasatinib also
      stimulated apoptosis in MDA-MB-468 cells, which could be attributed to activation
      of both caspase-9 and -8 and arrest of the cell cycle at G0/G1 cycle.
      Furthermore, dasatinib markedly inhibited colony formation, cell invasion,
      migration and angiogenesis, accompanied by decreased phosphorylation of EGFR and
      c-Src and their downstream effector molecules Akt and Erks. Our data suggest that
      dasatinib mediates its action in part through EGFR signaling and could be a
      potential therapeutic agent for breast cancer.

PMID- 19398151
TI  - Mechanism and kinetic considerations of TOC removal from the powdered activated
      carbon ozonation of diclofenac aqueous solutions.
AB  - Ozonation of DCF in aqueous solution in the presence of powdered activated carbon
      (PAC) has been studied for mechanistic and kinetic purposes. The effects of gas
      flow rate, ozone gas concentration and initial TOC on the TOC elimination rate
      were then investigated. The use of PAC allows liquid-solid and internal diffusion
      mass transfer resistances being eliminated. Gas-liquid mass transfer resistance
      is also eliminated when ozonation is applied to DCF preozonated solutions. In the
      absence of mass transfer resistances a mechanism of reactions involving
      homogeneous and heterogeneous steps for TOC removal was proposed. From this
      mechanism a mathematical model constituted by mass balances of main species in
      water was established. Considerations about the changing nature of ozonation
      intermediates, as being promoters or inhibitors of ozone decomposition, is a key
      point to better predict the experimental concentrations of species present in
      this system.

PMID- 19398152
TI  - Cadmium biosorption by polyvinyl alcohol immobilized recombinant Escherichia
      coli.
AB  - Recombinant Escherichia coli expressing human metallothionein protein was
      immobilized with polyvinyl alcohol (PVA) for the removal of cadmium from
      solution. The adsorption ability was strongly affected by pH with optimal
      performance at pH 5.0, while it was less sensitive to temperature over the range
      of 20-42 degrees C. The adsorption kinetics and equilibrium of PVA-immobilized
      cells was best described by pseudo-second order model and Langmuir isotherm,
      respectively. Over the Cd concentrations range of 10-150 mg/l, PVA-cells had the
      highest Cd removal percentage (82.7%) at 10mg Cd/l and a biomass loading of 15.4
      wt.%. Better adsorption ability was obtained when biomass loading was increased,
      as the highest adsorption capacity of 4.29 mg/g was achieved at 33.0 wt.% of
      biomass (initial Cd concentration=100mg/l). An aqueous solution of 0.01 M
      Na(3)NTA displayed the best desorption efficiency (57-89%) for four A/D cycles,
      while 51-61% of the original adsorption capacity was retained after regeneration.

PMID- 19398153
TI  - Evaluation of polymer inclusion membranes containing crown ethers for selective
      cesium separation from nuclear waste solution.
AB  - Transport behaviour of (137)Cs from nitric acid feed was investigated using
      cellulose triacetate plasticized polymer inclusion membrane (PIM) containing
      several crown ether carriers viz. di-benzo-18-crown-6 (DB18C6), di-benzo-21-crown
      7 (DB21C7) and di-tert-butylbenzo-18-crown-6 (DTBB18C6). The PIM was prepared
      from cellulose triacetate (CTA) with various crown ethers and plasticizers.
      DTBB18C6 and tri-n-butyl phosphate (TBP) were found to give higher transport rate
      for (137)Cs as compared to other carriers and plasticizers. Effect of crown ether
      concentration, nitric acid concentration, plasticizer and CTA concentration on
      the transport rate of Cs was also studied. The Cs selectivity with respect to
      various fission products obtained from an irradiated natural uranium target was
      found to be heavily dependent on the nature of the plasticizer. The present work
      shows that by choosing a proper plasticizer, one can get either good transport
      efficiency or selectivity. Though TBP plasticized membranes showed good transport
      efficiency, it displayed poor selectivities. On the other hand, an entirely
      opposite separation behaviour was observed with 2-nitrophenyloctylether (NPOE)
      plasticized membranes suggesting the possible application of the later membranes
      for the removal of bulk (137)Cs from the nuclear waste. The stability of the
      membrane was tested by carrying out transport runs for nearly 25 days.

PMID- 19398154
TI  - Contemplation on spark sensitivity of certain nitramine type explosives.
AB  - Spark sensitivity of explosives is an important subject. Presently, some
      correlations are sought between the spark sensitivity and certain molecular
      orbital characteristics of some nitramine type explosives. For that purpose
      certain semi-empirical and DFT calculations have been carried out. Investigations
      have revealed that the nitramines considered undergo decomposition in the
      electric field mainly via their anionic states.

PMID- 19398155
TI  - Characterization, ecological risk assessment and source diagnostics of polycyclic
      aromatic hydrocarbons in water column of the Yellow River Delta, one of the most
      plenty biodiversity zones in the world.
AB  - As one of the most active regions of land-ocean interaction among the large river
      deltas in the world, the Yellow River Delta (YRD) gains increasing concern on its
      ecological and environmental conditions. However, few studies on polycyclic
      aromatic hydrocarbons (PAHs) have been reported for this area. In this study, the
      distribution characteristics, probabilistic risk and possible sources of PAHs
      were investigated in the water column of the YRD. The PAH concentrations were
      found to be at relatively low or medium levels (121.3 ng L(-1) in water and
      209.1n g g(-1) in suspended particulate matter (SPM) on average), and the result
      of probability risk assessment additionally elucidated low PAH ecological risk in
      the YRD. The PAH composition showed that low and moderate molecular PAHs were the
      major species in water phase, whereas the SPM showed a different proportion of
      each PAH composition. An interesting result was found that low-ring PAHs and
      salinity in this land-ocean interaction area had a positive relationship
      (R=0.609). For PAH source identification, both diagnostic ratios of selected PAHs
      and principal component analysis (PCA) with multiple linear regression (MLR)
      analysis were studied, suggesting mixed sources of pyrogenic and petrogenic
      deriving PAHs in the YRD.

PMID- 19398156
TI  - Production of activated carbon by waste tire thermochemical degradation with CO2.
AB  - The thermochemical degradation of waste tires in a CO(2) atmosphere without
      previous treatment of devolatilization (pyrolysis) in order to obtain activated
      carbons with good textural properties such as surface area and porosity was
      studied. The operating variables studied were CO(2) flow rate (50 and 150
      mL/min), temperature (800 and 900 degrees C) and reaction time (1, 1.5, 2, 2.5
      and 3h). Results show a considerable effect of the temperature and the reaction
      time in the porosity development. Kinetic measurements showed that the reactions
      involved in the thermochemical degradation of waste tire with CO(2), are similar
      to those developed in the pyrolysis process carried out under N(2) atmosphere and
      temperatures below 760 degrees C, for particles sizes of 500 microm and heating
      rate of 5 degrees C/min. For temperatures higher than 760 degrees C the CO(2)
      starts to oxidize the remaining carbon black. Activated carbon with a 414-m(2)/g
      surface area at 900 degrees C of temperature, 150 mL/min of CO(2) volumetric flow
      and 180 min of reaction time was obtained. In this work it is considering the no
      reactivity of CO(2) for devolatilization of the tires (up to 760 degrees C), and
      also the partial oxidation of residual char at high temperature for activation
      (>760 degrees C). It is confirmed that there are two consecutive stages
      (devolatilization and activation) developed from the same process.

PMID- 19398157
TI  - Preparation and application of sustained release microcapsules of potassium
      ferrate(VI) for dinitro butyl phenol (DNBP) wastewater treatment.
AB  - The encapsulated potassium ferrate(VI) (K(2)FeO(4)) samples were successfully
      prepared by phase separation method in organic solvents. The ethyl cellulose and
      paraffin were selected for the microcapsule wall materials (WM). The as prepared
      microcapsules were characterized by X-ray diffraction (XRD) and Fourier transform
      infrared spectroscopy (FT-IR). The stability can be enhanced greatly when
      ferrate(VI) was encapsulated in the microcapsules with a mass ratio of Fe(VI):WM
      in the range of 1:1-1:3 for the same conserved time in air compared for pure
      K(2)FeO(4). The sustained release behavior of the microcapsules with different
      Fe(VI):WM mass ratios in 8.0M KOH solution was also investigated. The results
      indicated that the Fe(VI) release was reduced with increase of Fe(VI):WM mass
      ratios from 1:1 to 1:3. The release kinetics of the microcapsules is found to
      obey Ritger-Peppas equation. The prepared Fe(VI) microcapsules has been used for
      the removal of a typical alkyl dinitro phenol compound, 2-sec-butyl-4,6
      dinitrophenol (DNBP), from aqueous solution. The effect of pH, microcapsule
      concentration and reaction time was studied thoroughly. The optimal pH for DNBP
      degradation was 6.5, and at this pH and a microcapsule concentration of 1.2g/L,
      approximately 93% of the DNBP was degraded after 80 min. The encapsulated
      ferrate(VI) samples were found to be very effective in the decolorization and COD
      reduction of real wastewater from DNBP manufacturing. Thus, this study showed the
      feasible and potential use of encapsulated Fe(VI) samples in degradation of
      various toxic organic contaminants and industrial effluents.

PMID- 19398158
TI  - The impact of age on emotional and cognitive behaviours triggered by experimental
      neuropathy in rats.
AB  - Chronic pain syndromes encompass several clinical entities that frequently affect
      the individuals' emotional and cognitive behaviours which, in turn, can also
      alter pain perception. Additionally, both pain perception and motivational
      affective behaviours change with increasing age. In order to evaluate the
      influence of age upon the interaction between chronic pain and
      affective/cognitive behaviours, 3-, 10- and 22-month-old rats with 1 month
      neuropathy (spared nerve injury, SNI model) were compared with age-matched sham
      operated controls in the open field (OF; locomotor and exploratory behaviours),
      elevated plus-maze (EPM; anxiety-like behaviour), forced swimming (FST;
      depressive-like behaviour), working memory water maze (WM; spatial short-term
      memory), Morris water maze (MWM; spatial reference memory) and spatial reversal
      (behavioural flexibility) tests. Locomotor and exploratory activities decreased
      steadily with age and were further reduced by SNI. Aging was associated with
      increased anxiety-like behaviour, which was potentiated by SNI in both 3- and 22
      month-old rats. The performance in the FST was affected by SNI but only in mid
      aged animals. Cognitive performances in the MWM and spatial reversal tests
      deteriorated with age; however, the SNI lesion was only detrimental in the
      reversal task to mid-aged animals. Our data demonstrate that the influence of
      neuropathic pain on affective and cognitive behaviours is age dependent and
      varies with the behavioural domain that is tested. Importantly, mid-aged animals
      seem to be more susceptible to depression and cognitive deterioration associated
      to chronic pain than young and old groups.

PMID- 19398159
TI  - Climate and Dirofilaria infection in Europe.
AB  - Climatic changes, together with an increase in the movement of cats and dogs
      across Europe, have caused an increase in the geographical range of several
      vector borne parasites like Dirofilaria, and in the risk of infection for animals
      and humans. The present paper reviews the effects of climate and other global
      drivers on Dirofilaria immitis and Dirofilaria repens infections in Europe and
      the possible implications on the transmission and control of these mosquito-borne
      nematodes. In the last several years, growing degree day (GDD)-based forecast
      models, which use wide or local scale temperature data, have been developed to
      predict the occurrence and seasonality of Dirofilaria in different parts of the
      world. All these models are based on the fact that: there is a threshold of 14
      degrees C below which Dirofilaria development will not proceed; and there is a
      requirement of 130 GDD for larvae to reach infectivity and a maximum life
      expectancy of 30 days for a vector mosquito. The output of these models predicts
      that the summer temperatures (with peaks in July) are sufficient to facilitate
      extrinsic incubation of Dirofilaria even at high latitudes. The global warming
      projected by the Intergovernmental Panel on Climate Change suggests that warm
      summers suitable for Dirofilaria transmission in Europe will be the rule in the
      future decades and if the actual trend of temperature increase continues,
      filarial infection should spread into previously infection-free areas. These
      factors not only favour incubation of Dirofilaria, but also impact on mosquito
      species. Recent findings have also demonstrated that Aedes albopictus is now
      considered to be an important, competent vector of Dirofilaria infections. This
      mosquito species could spread from southern to northern European countries in the
      near future, changing the epidemiological patterns of dirofilariosis both in
      humans and animals.

PMID- 19398160
TI  - Efficacy of alphacypermethrin applied to cattle and sheep against the biting
      midge Culicoides nubeculosus.
AB  - The recent emergence of bluetongue virus (BTV) in northern Europe, has led to an
      urgent need to identify methods to control the Culicoides biting midges that
      transmit it. Here, an in vitro assay was used to assess the effects of the
      proprietary pyrethroid insecticide alphacypermethrin applied to cattle and sheep
      (Dysect Cattle Pour-On, Dysect Sheep Pour-On; Ford Dodge Animal Health) against
      the biting midge Culicoides nubeculosus (Meigen) (Diptera: Ceratopogonidae). Hair
      or wool was collected from the back, belly and legs of animals immediately prior
      to treatment and 7, 14, 21, 28 and 35 days after treatment, and also from
      untreated controls. In the laboratory assay groups of 10 adult females C.
      nubeculosus were exposed to 0.5 g of hair or wool for 3 min. In all cases, no
      mortality was observed in the pre-treatment sample or the untreated controls. In
      the post-treatment samples, for both cattle and sheep mortality was close to 100%
      7 days after treatment. For cattle, treatment effect persisted for up to 21 days
      post-treatment, following which the mortality rate following exposure to hair
      samples declined. In contrast, for sheep, mortality levels declined more slowly,
      and approximately 50% mortality was still observed 35 days after treatment. There
      was no significant difference in the kill rate for wool collected from the back,
      belly or legs of either sheep or cattle. The results demonstrate the potential
      for pour-on insecticide treatment to offer a degree of mitigation to livestock
      against onward transmission from infected animals--and in particular demonstrate
      that sufficient compound is able to reach the lower legs to kill in contact
      midges. The practical issues associated with achieving adequate protection are
      discussed.

PMID- 19398161
TI  - Brief screens for detecting alcohol use disorder among 18-20 year old young
      adults in emergency departments: Comparing AUDIT-C, CRAFFT, RAPS4-QF, FAST, RUFT
      Cut, and DSM-IV 2-Item Scale.
AB  - BACKGROUND: This study compared six of the briefest screening instruments for
      detecting DSM-IV-defined Alcohol Use Disorder (AUD) among older adolescents
      treated in Emergency Departments (ED). METHODS: The AUDIT-C, the RAPS4-QF, the
      FAST, the CRAFFT, the RUFT-Cut, and 2-Items from the Diagnostic and Statistical
      Manual IV of the American Psychiatric Association [American Psychiatric
      Association (1994). Diagnostic and Statistical Manual of Psychiatric Disorders,
      (1994) (DSM-IV). 4th ed. Washington D.C.: American Psychiatric Association]
      criteria for AUD (heretofore referred to as the DSM-IV 2-Item Scale) were
      evaluated against the criterion of a current DSM-IV diagnosis of either alcohol
      abuse or dependence. The instruments were administered to 181 alcohol-using older
      adolescents (57% males; age range 18-20 years) in an ED and compared using
      Receiver Operator Characteristic (ROC) analyses against the criterion of a
      current DSM-IV diagnosis of alcohol abuse or dependence. RESULTS: Of these
      instruments, the DSM-IV 2-Item Scale performed best for identifying AUD (88%
      sensitivity and 90% specificity), followed by the FAST and the AUDIT-C.
      CONCLUSIONS: Two items from the DSM-IV criteria for AUD performed best for
      identifying ED-treated older adolescents with alcohol use disorders. The FAST and
      AUDIT-C performed well, but are longer and more difficult to score in the hectic
      environment of the Emergency Department.

PMID- 19398162
TI  - Victimization from mental and physical bullying and substance use in early
      adolescence.
AB  - Logistic regression analyses were used to assess the association between
      victimization from mental and physical bullying and use of alcohol, cigarettes,
      marijuana, and inhalants among middle school students. Self-report data were
      analyzed from 926 ethnically diverse sixth through eighth grade students (43%
      White, 26% Latino, 7% Asian American/Pacific Islander, 3% African American, 14%
      mixed ethnic origin, and 5% "other") ages 11-14 years from southern California.
      Substance use was collected at two time points (fall 2004 and spring 2005) during
      an academic year. Models were run for each substance separately. Results
      supported an association between victimization from bullying and substance use.
      Youths who experienced each type of bullying (mental or physical) separately or
      in combination were more likely to report use of each substance in spring 2005.
      This finding held after controlling for gender, grade level, ethnicity and
      substance use in fall 2004.

PMID- 19398163
TI  - Neurocognitive profiles of people with comorbid depression and alcohol use:
      implications for psychological interventions.
AB  - Depression and alcohol use disorders frequently co-occur and are highly
      prevalent. Both conditions are known to impair cognitive functioning, yet
      research into the role of these impairments in response to Cognitive Behaviour
      Therapy (CBT) is limited. The purpose of the present study was to examine the
      relationship between baseline neuropsychological performance, severity of
      depressive symptoms and alcohol use disorders. Participants with current
      depression and hazardous alcohol use were functioning in the average range on all
      neuropsychological measures prior to treatment entry. Baseline measures of
      drinking severity and a range of cognitive functions were inversely correlated.
      After controlling for other baseline variables, superior baseline cognitive
      functioning predicted greater reductions in depression severity after 17 weeks.
      These predictive effects occurred across both brief and extended interventions.
      Findings suggest that improvement in depression following psychological treatment
      is enhanced by greater fluid reasoning ability and is predicted by executive
      functioning, regardless of the treatment length or problem focus.

PMID- 19398165
TI  - Emerging adult outcomes of adolescent psychiatric and substance use disorders.
AB  - This study investigates the age 25 outcomes of late adolescent mental health and
      substance use disorders. A hierarchical cluster analysis of age 19 DSM-III-R
      mental health and substance diagnoses placed participants into one of 9 clusters:
      Anxious, Depressed, Antisocial, Drug Abuser, Problem Drinker, Anxious Drinker,
      Depressed Drug Abuser and Antisocial Drinker, and No Diagnosis. Diagnoses were
      generated from the University of Michigan Composite International Diagnostic
      Interview. Repeated measures multivariate analyses of variance revealed distinct
      trajectories of improvement and decline among the 9 clusters. Clusters with co
      occurring substance and mental health disorders improved over adolescent levels,
      but continued to have higher levels of depression symptoms, poorer global
      functioning, and higher levels of substance use than the No Diagnosis cluster.
      Members of the The Problem Drinkers cluster, who tended to have alcohol use
      disorders only at age 19, did not differ from their peers with no diagnoses. Drug
      use disorders in adolescence, with or without a co-occurring mental health
      disorders, were associated with a poor prognosis in emerging adulthood. Clinical
      interventions should distinguish among these diverse clinical presentations.

PMID- 19398164
TI  - Illicit use of pharmaceutical opioids among young polydrug users in Ohio.
AB  - This study, conducted in Columbus, Ohio, identified the predictors of current
      (past 30 day) illicit use of pharmaceutical opioids among young individuals
      (n=402) with a history of MDMA/ecstasy use who were recruited in 2002-2003 using
      respondent-driven sampling. To be eligible, participants had to be 18-30 years
      old, not involved in a drug abuse treatment, and report MDMA/ecstasy use at least
      once in the past 6 months. About 81% reported lifetime, and more than 31%
      reported current illicit use of pharmaceutical opioids. Logistic regression
      analysis revealed that illicit use of pharmaceutical tranquilizers and
      pharmaceutical stimulants were the strongest predictors of illicit use of
      pharmaceutical opioids. Risk of pharmaceutical opioid use was also greater among
      those who had higher levels of depressive symptoms and reported current use of
      hallucinogens and inhalants. Our findings suggest that the non-medical use of
      pharmaceutical opioids is a part of polydrug use practices that often incorporate
      illicit use of other prescription drugs. The observed relationship between
      depressive symptoms and illicit use of pharmaceutical opioids may have important
      implications for prevention programming and should be examined in future
      research.

PMID- 19398167
TI  - Schizophrenia, cancer and the "Red Queen" co-evolutionary dynamics.

PMID- 19398166
TI  - Nicotine withdrawal and craving in adolescents: effects of sex and hormonal
      contraceptive use.
AB  - While sex differences in the nicotine withdrawal (NW) symptoms and craving (NC)
      have been extensively described in adult cigarette smokers, few studies have
      investigated these phenomena in adolescents. We investigated the effect of gender
      and hormonal contraception (HC) on NW and NC during the first 14 days of
      cessation in adolescent smokers using data from a randomized, placebo-controlled,
      double-blind trial of the transdermal nicotine replacement therapy for smoking
      cessation. Analyses showed similar levels of NW severity in males and females,
      regardless of HC use. However, significantly higher NC was observed in females
      compared to males, (2.22+/-0.12 vs. 1.65+/-1.14; p=0.003). Further, females not
      using HC reported the highest level of NC (2.38+/-0.16) followed by females using
      HC (2.08+/-0.25) and males (1.71+/-0.16; p=0.007). The current findings suggest
      that adolescent females experience similar NW severity to males, but have
      stronger NC. Further, the use of hormonal contraceptives may impact the severity
      of craving. Addressing these different symptoms in adolescents may be useful in
      increasing smoking cessation rates in this special population of smokers.

PMID- 19398168
TI  - Therapy with noninvasive ventilation in patients with obstructive sleep apnoea:
      effects on atherogenic lipoprotein phenotype.
AB  - Patients with obstructive sleep apnoea are at increased risk of atherosclerotic
      morbidity and mortality. Abnormalities in lipid metabolism that occur in response
      to chronic intermittent hypoxia in patients with sleep-disordered breathing may
      increase the cardiovascular risk in an already susceptible population.
      Atherogenic lipoprotein phenotype and small, dense LDL have an independent
      predictive role for future cardio- and cerebro-vascular events in patients with
      the metabolic syndrome. Therefore, testing the hypothesis that therapy of
      obstructive sleep apnoea may reduce atherogenic lipoprotein phenotype might have
      significant clinical implications. We suggest that abolition of obstructive sleep
      apnoea by continuous positive airway pressure results in reductions in
      circulatory levels of small, dense LDL by improvements in oxygen saturation,
      reductions in oxidative stress, improvements in insulin sensitivity, and
      reductions in triglyceride biosynthesis. Testing the proposed hypothesis may
      contribute to improvements in clinical management of patients with obstructive
      sleep apnoea by early recognition of atherogenic dyslipidaemia followed by both,
      vigorous treatment of the underlying sleep-disordered breathing by noninvasive
      ventilation and targeted therapeutic modulation of hypertriglyceridaemia, low HDL
      cholesterol and increased levels of small, dense LDL. Implementing this strategy
      to patients with obstructive sleep apnoea may potentially contribute to
      substantial reduction of their high cardiovascular risk.

PMID- 19398169
TI  - PI-PLC signal pathway: a possible pathogenesis link post-myocardial infarction to
      depression.
AB  - Depressive disorder in the post-myocardial infarction (MI) period has been
      associated with increased cardiac morbidity and mortality. The most prominent
      findings are the increased mortality in patients with depression after myocardial
      infarction. Despite the extensive studies, the possible pathophysiologic
      mechanisms behind this association have not been clear. More recently, the data
      have suggested that both depression and post-MI have been associated with an
      increased activation status of the platelet. And increased sensitivity to
      platelet activation has been postulated as one of the mechanisms that may
      underlie increased vulnerability of depressed post-MI patients to cardiac events,
      suggesting a pathophysiologic cross-talk between the heart and the brain.
      Considering the similar changes in serotonin(5-HT) and platelet activation
      through phosphoinositide (PI)-phospholipase C(PLC) pathway, we guess that PI-PLC
      signal transduction pathway is a common pathogenesis between depression and post
      MI, which mediated by 5-HT resulting in the platelet activation. The article
      introduces the hypothesis that proposes one possibility. This common mechanism of
      signal pathway may develop other current theories which are beneficial to future
      therapies to reduce post-MI depression.

PMID- 19398170
TI  - Prevention of orthogonal array of particles formation as a treatment approach for
      neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is an uncommon, life-threatening demyelinating disease
      that produces transverse myelitis and optic neuritis. An important pathogenetic
      mechanism belongs to NMO-IgG autoantibodies directed against the ultrastructure
      of the water channel aquaporin-4 (AQP4), the so-called orthogonal arrays of
      particles (OAPs). With respect to the yet known data about OAP formation it is
      suggested to modulate the AQP4-M23 isoform to prevent the aggregation of AQP4
      tetramers into higher organized structures. Without specific target for the NMO
      IgGs the inflammation and thus the resulting demyelination may be stopped without
      the need for immunosuppressive agents with severe side-effects.

PMID- 19398171
TI  - Novel swine influenza virus subtype H3N1 in Italy.
AB  - To date, three subtypes of swine influenza viruses, H1N1, H1N2, and H3N2 have
      been isolated in Italy. In 2006, a novel swine influenza virus subtype (H3N1) was
      isolated from coughing pigs. RT-PCR performed on lung tissues, experimental
      infection in pigs with the novel isolate, and cloning the virus by plaque assay
      confirmed this unique H and N combination. The novel isolate was also
      antigenically and genetically characterized. Genetic and phylogenetic analysis
      showed that the complete HA gene of the H3N1 strain has the highest nucleotide
      identity to three Italian H3N2 strains, one isolated in 2001 and two in 2004,
      whereas the full length NA sequence is closely related to three H1N1 subtype
      viruses isolated in Italy in 2004. The remaining genes are also closely related
      to respective genes found in H1N1 and H3N2 SIVs currently circulating in Italy.
      This suggests that the novel SIV could be a reassortant between the H3N2 and H1N1
      SIVs circulating in Italy.

PMID- 19398173
TI  - "Orthograde entrance technique" to recover DNA from ancient teeth preserving the
      physical structure.
AB  - Milling methods utilized by molecular researchers destruct the morphological
      structure of ancient teeth, crucial in anthropological evaluation. This causes
      researchers to be reluctant to try DNA analyses. Retrograde, reverse root canal
      technique, which is from root apex to the tooth crown, provides both a dentine
      rich sample and a procedure that overcomes this problem. However, this technique
      has some disadvantages due to the relatively fragile, permeable and weak nature
      of the tooth root. On the other hand, "orthograde entrance technique", straight
      from tooth crown to the root apex, both preserves the morphological structure and
      deals with the problems related to the root structure by providing an entrance
      from the enamel surface. Moreover comparable amplification results to prior
      studies in the literature were also achieved.

PMID- 19398172
TI  - Bone mineral density in healthy Tunisian women.
AB  - Interpretation of densitometric results requires a comparison with reference bone
      mineral density (BMD) values of normal age and sex-matched persons. Thus the aim
      of this study was to determine these values for healthy Tunisian women, to
      estimate the prevalence of osteoporosis and to compare our findings with other
      populations. A cross-sectional study of 1378 Tunisian women aged between 20 and
      96 years was carried out using DXA (GE-Lunar Prodigy). Subjects with suspected
      conditions affecting bone metabolism were excluded. Measurements were taken at
      the lumbar spine and femoral neck. These values were expressed at T-scores, with
      reference to the mean BMD values of the group aged 20-40 years. The peak bone
      mass, estimated in this age group was 1.174+0.127 g/cm(2) at the lumbar spine and
      1.016+/-0.118 g/cm(2) at the femoral site. It was attained respectively within
      the age of 25 years and 36 years. For both sites, the expected decline in BMD was
      shown when the successive age groups [40-49 years] and [50-59 years] were
      compared. Bone loss was rapid during the first 5 years after menopause.
      Thereafter BMD declined slowly but continually. The prevalence of osteoporosis in
      the women over 50 years of age, taking account of peak bone mass observed in our
      cohort, was 23.3% at the spine and 17.3% at the femoral neck with a combined
      prevalence of 23.4%. These rates attained respectively 30.4%, 11.8% and 32.9%
      when we considered the Italian values, which demonstrate the variability of
      osteodensitometric depending to the reference population adopted.

PMID- 19398174
TI  - Frequency of osteoporosis in 46 men with methamphetamine abuse hospitalized in a
      National Hospital.
AB  - BACKGROUND: Methamphetamine, a derivative of amphetamine, has been well known to
      cause mental problems in humans; however, its physical effects are little known.
      Despite relevant information on the effect of methamphetamine abuse on bone
      quality being available, data regarding the frequency of osteoporosis in
      methamphetamine abusers are limited. METHODS: We selected 46 hospitalized male
      methamphetamine abusers and 188 reference male controls in whom any conditions
      affecting bone metabolism were ruled out. Bone mineral density (BMD) in the
      lumbar spine was measured by dual energy X-ray absorptiometry (DXA). We compared
      the BMD between methamphetamine abusers and controls and evaluated the frequency
      of osteoporosis in both groups. RESULTS: The mean BMD value was lower in
      methamphetamine abusers (mean+/-SD, 0.71+/-0.07 g/cm(2)) than in the controls
      (mean+/-SD, 0.98+/-0.14 g/cm(2)). The frequency of osteoporosis was 22% according
      to WHO diagnostic guidelines, and osteopenia at the lumbar spine was 76%. The
      correlation between the extent of methamphetamine abuse and BMD was very clear.
      CONCLUSION: There was considerable loss of bone mineral in a high percentage of
      methamphetamine abusers. Our study is the first clinical study to determine the
      frequency of osteoporosis in male methamphetamine abusers.

PMID- 19398175
TI  - Localization and infliction pattern of iatrogenic skull base defects following
      endoscopic sinus surgery at a teaching hospital.
AB  - OBJECTIVE: Aim of this study is to evaluate the incidence, infliction patterns
      and management of dural injuries with cerebrospinal fluid (CSF) rhinorrhea
      following endoscopic sinus surgery at a teaching hospital. We present our results
      of over 14 years of experience from endoscopic repair of CSF rhinorrhea with long
      term follow-up. METHODS: A retrospective study was performed by screening 14
      years of sinus surgeries for iatrogenically inflicted CSF leaks of the anterior
      skull base. Obtained data were analyzed to determine the infliction pattern and
      location of CSF leaks, surgical closure techniques and outcomes. All incidences
      were further evaluated with regards to the surgeons training status. RESULTS: 144
      patients out of 6908 sinus surgeries were diagnosed with CSF rhinorrhea and
      underwent subsequent surgical repair. 52 patients had iatrogenic CSF leaks with
      32 of the defects inflicted by the department's physician personnel. Average
      follow-up was 62 months, with a range of 10-168 months. The side distribution was
      56.3% to the patient's right side and in 40.6% to the patient's left side. 68.7%
      became apparent during the initial surgery whereas 31.3% only after surgery. The
      most common defect location was the anterior ethmoid at the attachment of the
      medial concha base with 43.7%, followed by the junction between the ethmoid and
      sphenoid sinus with 21.9%, the frontal sinus aditus with 18.7% and the medial
      ethmoid region with 9.4%. With increasing training status, surgeons were more
      prone to cause defects at the frontal sinus aditus whereas surgeons with lesser
      training status caused more defects at the anterior ethmoid at the medial concha
      base. The posterior ethmoid and sphenoid sinus was equally prone to defects over
      all stages of surgical training. Initial endoscopic repair was successful in
      87.5% of patients and 95% after revision surgery. CONCLUSION: The obtained data
      confirm the safety of the endonasal sinus surgery according to Wigand's
      technique. The incidence of iatrogenic CSF leaks at a teaching hospital is not
      higher than at specialized rhinology departments. We observed a distinct pattern
      of inflicted skull base defects with different hot-spot areas, prone to damage in
      various stages of the surgeon's status of expertise.

PMID- 19398176
TI  - Multiple system atrophy manifesting as complex sleep-disordered breathing.
AB  - A 56-year-old female presented with multiple system atrophy (MSA) and pure
      obstructive sleep-disordered breathing (SDB) with an apnea hypopnea index of
      29.6/h. However, after the elimination of obstructive events, central apneas
      emerged with a central apnea index (CAI) of 45.3/h as determined by continuous
      positive airway pressure titration. Adaptive servoventilation titration decreased
      the CAI; however, it remained at 14.2/h. There are two different underlying
      causes of SDB in MSA patients, one is upper airway obstruction at the glottic
      level, and the other is central components owing to the degeneration of the
      pontomedullary respiratory centers. Clinicians should recognize that whether a
      patient has central apnea cannot be determined by diagnostic polysomnography but
      only after the elimination of upper airway obstruction in MSA patients.

PMID- 19398177
TI  - Evaluation of the polymorphism in the Toll-like receptor 4 (TLR4) genes of
      tympanosclerosis patients.
AB  - OBJECTIVE: Although eardrum perforations which endure etiopathogenesis for a long
      time and middle ear infections are proposed for causing the tympanosclerosis
      (TS), tympanosclerosis emerges in some chronic otitis media (COM), some of them
      do not appear although a continuing COM and enduring perforation last. In this
      study, the effect of the molecular reasons which display genetic differences in
      TS formation is evaluated; our aim is to determine the Asp299Gly polymorphism
      frequencies in the TLR4 gene of patients with TS who have COM, and patients who
      do not. MATERIALS AND METHODS: Patients who have undergone COM surgery, were
      divided into two groups of 50 persons who were selected in accordance with the
      fact, whether they had TS in their middle ear cavity or not during operation. 100
      healthy persons who had similar demographic data, were evaluated as the control
      group. The DNA isolation was executed by using standard methods with peripheric
      blood specimen of the diseased group and control group. The Restriction Fragment
      Length Polymorphism method was used in determining the Asp299Gly allel in the
      TLR4 gene. Items of 249 bc for the wild tip (Asp) post-restriction enzyme segment
      wild tip (Asp) allel, and 23 bc and 196 bc post-restriction enzyme segment
      polymorphic allel (Gly) were obtained. RESULTS: TLR4 Asp299Gly polymorphism (10%)
      was asserted in a total of five specimens in the diseased group with TS. TLR4
      Asp299Gly polymorphism was found positive in only one (2%) of the 50 phenomenons
      in the group without TS. TLR4 Asp299Gly polymorphism was found positive in six
      (6%) of the 100 phenomenons in the control group. The positive polymorphism in
      phenomenons with TS was significant in accordance with statistics, when compared
      with the group without TS (p<0.05). However, although the polymorphism rates were
      higher than the rates of the control group, it was not statistically significant
      (p>0.05). CONCLUSION: TS may not appear in many patients who had undergone middle
      ear infection, and had perforation for many years. The polymorphism in
      arteriosclerosis in the TLR4 gene which caused the inflammatory cytokines
      oscillation recognize the bacterial LPS, was also accused. It is engrossing to
      find out from the results of our study on a restricted number of patients, and on
      only one gene, that molecular reasons which display genetic differences can also
      be effective in forming TS. Serial researches of greater dimensions are required.

PMID- 19398178
TI  - Positional and positioning down-beating nystagmus without central nervous system
      findings.
AB  - We report the clinical features of 4 cases with positional or positioning down
      beating nystagmus in a head-hanging or supine position without any obvious
      central nervous system disorder. The 4 cases had some findings in common. There
      were no abnormal findings on neurological tests or brain MRI. They did not have
      gaze nystagmus. Their nystagmus was observed only in a supine or head-hanging
      position and it was never observed upon returning to a sitting position and never
      reversed. The nystagmus had no or little torsional component, had latency and
      tended to decrease with time. The positional DBN (p-DBN) is known to be
      indicative of a central nervous system disorder. Recently there were some reports
      that canalithiasis of the anterior semicircular canal (ASC) causes p-DBN and that
      patients who have p-DBN without obvious CNS dysfunction are dealt with anterior
      semicircular canal (ASC) benign paroxysmal positional vertigo (BPPV). There are
      some doubts as to the validity of making a diagnosis of ASC-BPPV in a case of p
      DBN without CNS findings. It is hard to determine the cause of p-DBN in these
      cases.

PMID- 19398179
TI  - Revision surgery for chronic otitis media: characteristics and outcomes in
      comparison with primary surgery.
AB  - OBJECTIVES: To analyze the characteristics and outcomes of revision surgery for
      chronic otitis media (COM) with or without cholesteatoma, and to compare with
      those of primary surgery. METHODS: A retrospective chart review was performed on
      208 patients who underwent revision surgery for COM over an 8-year period (1997
      2004) and 51 patients who underwent a primary canal wall down mastoidectomy
      (CWDM), and were followed for more than 12 months. RESULTS: Recurrent or residual
      cholesteatoma was found in 49.5% of cases. The mastoid tip and perisinal air
      cells were the most frequent sites of residual air cells. As a result of revision
      surgery, a dry and safe ear was achieved in 88.5% of patients. A residual air
      bone gap (ABG) of <or=30 dB was achieved in 70.1% of cases with a revision CWDM
      with ossiculoplasty. In comparison with 51 patients who underwent primary CWDM,
      the disease control rate was not different. However, postoperative hearing result
      after ossiculoplasty was worse and longer healing time was required after
      revision surgery. CONCLUSION: The characteristics and surgical outcome of
      recurrent COM must be fully understood for complete control of the disease.

PMID- 19398180
TI  - The role of hypoxia-inducible transcription factors in the hypoxic neonatal
      brain.
AB  - Hypoxia-inducible transcription factors (HIF)-1 and HIF-2, composed of an oxygen
      dependent alpha-subunit and a constitutive beta-subunit, have been characterized
      as the most important regulators of oxygen homeostasis during physiological and
      pathological conditions. During embryonic, fetal and postnatal brain development,
      HIFs and specific HIF target genes are involved in early and highly active
      maturational processes by modulating cell differentiation, vascular development,
      angiogenesis and metabolic homeostasis. Under hypoxic conditions, activation of
      the HIF system reflects an immediate and cell-specific response to acute brain
      hypoxia. In a complementary fashion, both HIF-1 and HIF-2 modulate cerebral
      hypoxic stress responses and activate endogenous neuroprotective systems during
      acute and late stages of hypoxic/ischemic (HI) damage of the developing brain.
      Therefore, HIFs and their specific target genes that are expressed during brain
      injury are of particular interest for future diagnostic and therapeutic options
      in HI injury of the developing nervous system.

PMID- 19398181
TI  - Sonic hedgehog (SHH) mutation in patients within the spectrum of
      holoprosencephaly.
AB  - Holoprosencephaly (HPE) is a malformation sequence where the cerebral hemispheres
      fail to separate into distinct left and right halves. It can be associated with
      midline structural anomalies of the central nervous system and/or face. SHH is
      the major gene implicated in HPE and it plays a critical role in early forebrain
      and central nervous system development. SHH is expressed in the human embryo in
      the notochord, the floorplate of the neural tube, and the posterior limb buds. In
      the present study we performed mutational analysis of the entire coding region of
      the SHH gene in 37 unrelated individuals with the HPE spectrum. Three different
      variants were found throughout the extent of the gene. No genotype-phenotype
      correlation is evident based on the type or position of the mutations. This study
      confirms the great genetic heterogeneity of the disease and the difficulty to
      establish genotype-phenotype correlations.

PMID- 19398182
TI  - Superior cerebellar artery infarction in endovascular treatment for tentorial
      dural arteriovenous fistulas.
AB  - BACKGROUND: Superior cerebellar artery (SCA) syndrome shows ipsilateral
      cerebellar ataxia and Horner's syndrome, contralateral superficial sensory
      disturbance, as well as nystagmus toward the impaired side, vertigo, and nausea.
      Occasionally, unilateral lesions may produce bilateral hypogeusia and
      contralateral hypoacusia. OBJECTIVE: To report 2 patients with unilateral lower
      midbrain ischemic lesions of the inferior colliculus level caused by
      transarterial embolization for tentorial dural arteriovenous fistulas (TDAVFs).
      METHODS: Hospital records for 21 patients with TDAVFs mainly treated by
      endovascular techniques between 2005 and 2008 were reviewed. Two patients with
      MRI evidence of unilateral SCA territory infarction were investigated. RESULTS:
      Of 21 patients, 2 treated transarterially with Onyx-18 (a nonahesive liquid
      embolic agent) developed infarctions in the territory of SCA. One patient had
      lateral SCA infarction characterized by ipsilateral gait ataxia, contralateral
      hemihypoesthesia, with additional ipsilateral ocular motor palsy and bilateral
      gustatory loss. And the other patient had medial SCA infarction characterized by
      ipsilateral ataxia contralateral hemihypoesthesia with additional contralateral
      hypoacusia. CONCLUSION: SCA infarction can be caused by transarterial injection
      of Onyx-18 via SCA or the posterior cerebral artery (PCA) for TDAVFs and
      additionally presented with gustatory loss and deafness, which is generally not a
      feature of the SCA syndrome.

PMID- 19398183
TI  - PROTECT carotid artery stenting study.

PMID- 19398184
TI  - Regarding "National outcomes for the treatment of ruptured abdominal aortic
      aneurysm: comparison of open versus endovascular repairs".

PMID- 19398185
TI  - Credentialing and training of CREST stentors.

PMID- 19398186
TI  - Trends in workforce diversity in vascular surgery programs in the United States.
AB  - BACKGROUND: U.S. black and Hispanic populations are growing at a steady pace. In
      contrast, the medical profession lacks the same minority growth and
      representation. Women are also under-represented in many surgical disciplines.
      The purpose of this study was to assess trends in the proportion of women,
      blacks, and Hispanics admitted to vascular surgery (VS) and related specialties,
      and to compare them with each other and with a surgical specialty, orthopedic
      surgery (OS), with a formal diversity initiative. METHODS: Data on the fellowship
      pool of VS, interventional radiology (IR), and interventional cardiology (IC), as
      well as the resident pools of general surgery (GS) and orthopedic surgery (OS),
      were obtained from U.S. graduate medical education reports for 1999 through 2005.
      Cochrane-Armitage trend tests were used to assess trends in the proportion of
      females, blacks, and Hispanics in relation to the total physician workforce for
      each subspecialty. RESULTS: No significant trends in the proportion of females,
      blacks, or Hispanics accepted into VS and IC fellowship programs occurred during
      the study period. In contrast, IR, GS, and OS programs revealed significant
      trends for increasing proportions of at least one of the underrepresented study
      groups. In particular, OS, which has implemented a diversity awareness program,
      showed a positive trend in female and Hispanic trainees (P < .04 and P < .02,
      respectively). Blacks showed a significant increasing trend only in IR (P = .05).
      Conversely, a positive trend toward continued growth in the Hispanic group was
      seen in GS (P < .001), IR, and OS (P = .04 and P = .02, respectively).
      CONCLUSIONS: The racial/ethnic and gender composition of the physician trainee
      pool in vascular specialties, particularly VS, has not matched the increasing
      growth of underrepresented groups in the US population of patients with vascular
      disease. Formal programs to recruit qualified women and minorities appear
      successful in increasing workforce diversity.

PMID- 19398187
TI  - Two-year follow-up results of the SPACE study.

PMID- 19398188
TI  - Surgical resection of the primary tumour is associated with improved survival in
      patients with distant metastatic breast cancer at diagnosis.
AB  - OBJECTIVE: Recent studies indicate that removal of the primary tumour may have a
      beneficial effect on mortality risk of patients with primary distant metastatic
      breast cancer (stage IV), although most of them did not rule out confounding by
      the presence of co-morbidity. In this retrospective study the impact of surgical
      resection of the primary tumour on the survival of patients with primary distant
      metastatic disease is investigated, taking into account the presence of co
      morbidity and other potential confounders. METHODS: Between 1993 and 2004, 15 769
      patients with breast cancer were diagnosed in the south of the Netherlands. This
      study included the 728 patients with distant metastatic disease at initial
      presentation, which was 5% of all patients. Of them, 40% had surgery of the
      primary tumour. Follow-up was carried out until 1 July 2006. RESULTS: Median
      survival of the patients who had surgery of their primary tumour was
      significantly longer than for the patients who did not have surgery (31 vs. 14
      months). The 5-year survival rates were 24.5% and 13.1%, respectively (p <
      0.0001). In a multivariable Cox regression analysis, adjusting for age, period of
      diagnosis, T-classification, number of metastatic sites, co-morbidity, use of
      loco-regional radiotherapy and use of systemic therapy, surgery appeared to be an
      independent prognostic factor for overall survival (HR = 0.62; 95% CI 0.51-0.76).
      CONCLUSION: Removal of the primary tumour in patients with primary distant
      metastatic disease was associated with a reduction of the mortality risk of
      around 40%. The association was independent of age, presence of co-morbidity and
      other potential confounders, but a randomized controlled trial will be needed to
      rule out residual confounding.

PMID- 19398189
TI  - Congenital subclavian arteriovenous malformation causing cardiac failure in an
      adult.
AB  - Congenital arteriovenous malformations (AVMs) of the thoracic region are rarely
      reported in adults. The authors report an unusual case of a 30-year-old man who
      presented with a large congenital AVM and heart failure. The diagnosis was made
      using transthoracic Doppler echocardiography and computed tomography.
      Embolization followed by surgical resection of the AVM resulted in the prompt
      relief of heart failure.

PMID- 19398191
TI  - Intraoral removal of proximal submandibular stones--an alternative to
      sialadenectomy?
AB  - Submandibular salivary stones account for most symptomatic sialoliths and most
      are treated by adenectomy. Transoral removal of proximal or hilar stones is an
      alternative approach that preserves the functioning gland. Between 1999 and 2006,
      186 consecutive patients had transoral removal of 186 stones in the proximal
      third or hilum of the submandibular gland. Both patient and treatment details
      were recorded prospectively and outcome assessed by a structured questionnaire.
      Stone removal was achieved in 99% (185/186) of cases treated. Morbidity was low
      and there were no intra-operative complications. At median follow up of 28 months
      (range 4-62 months) 4% (7/186) had subsequently undergone sialadenectomy for
      persisting symptoms. 105/186 responded to a questionnaire, 76% (80/105) were
      symptom-free and in a further 17% (18/105) symptoms were mild. No patient had
      lingual nerve anaesthesia but 6% (6/105) reported a mild tingling. 93% (97/105)
      were pleased to have had the operation. Submandibular stones can be reliably
      retrieved from the proximal portion of the duct or hilum with minimal morbidity.
      Evolving review data suggests that the incidence of recurrent disease is low at 2
      years, suggesting that this technique may be a viable alternative to adenectomy.

PMID- 19398190
TI  - Polyreactive autoantibodies in systemic lupus erythematosus have pathogenic
      potential.
AB  - The present study was undertaken to determine whether germline encoded and
      polyreactive antibodies might be pathogenic and whether the breach of early
      tolerance checkpoints in systemic lupus erythematosus (SLE) might lead to a
      population of B cells expressing germline encoded antibodies that become
      pathogenic merely by class switching to IgG in a pro-inflammatory milieu. We
      demonstrate here that IgM, DNA-reactive antibodies obtained from lupus patients
      that are unmutated and display polyreactivity can bind to isolated glomeruli and
      exhibit neurotoxic potential. Thus, the IgM polyreactive repertoire in SLE
      includes antibodies that may acquire pathogenic function merely by undergoing
      class-switch recombination to become IgG antibodies.

PMID- 19398192
TI  - Metabolic profiles of second-generation antipsychotics in early psychosis:
      findings from the CAFE study.
AB  - OBJECTIVE: To further define the metabolic profiles of second-generation
      antipsychotics during the treatment of young patients with early psychosis, with
      a view to better inform prescribing clinicians. METHOD: Weight, body mass index
      (BMI), glucose, and serum lipids were measured in the 52-week Comparison of
      Atypicals for First Episode (CAFE) study, in which olanzapine, quetiapine, and
      risperidone were evaluated, and whose primary outcomes have been reported
      elsewhere. These metabolic data were analyzed using a mixed random coefficients
      model for continuous longitudinal measures and a logistic regression model for
      categorical responses. RESULTS: Of the 400 patients recruited, 31% were
      overweight and 18% were obese at baseline, and 17 (4.3%) patients met criteria
      for metabolic syndrome. After 12 and 52 weeks of treatment, weight gain >or=7%
      from baseline was reported in 29.2% and 50.0% of quetiapine-treated patients,
      59.8% and 80.0% of olanzapine-treated patients, and 32.5% and 57.6% of
      risperidone-treated patients, respectively. Weight gain after 12 and 52 weeks of
      treatment was estimated as [Least Squares Mean (SE)] 15.6 (+/-1.1) and 24.2 (+/
      1.9) lb for olanzapine, 8.6 (+/-1.1) and 14.0 (+/-1.9) lb with risperidone and
      7.9 (+/-1.1) and 12.1 (+/-1.8) lb for quetiapine respectively. In women, greater
      weight gain occurred during risperidone treatment compared with quetiapine
      treatment. By week 52, increases in BMI >or=1 unit occurred with significantly
      higher frequency in olanzapine-treated patients compared with quetiapine- or
      risperidone-treated patients. By 52 weeks, treatment-emergent metabolic syndrome
      was reported in 51 individuals (13.4% of the total population), of whom 22 were
      receiving olanzapine, 18 quetiapine, and 11 risperidone. Risperidone was
      associated with the smallest elevations in triglyceride and total cholesterol
      levels. CONCLUSION: Weight gain and metabolic syndrome occur commonly even in
      young patients receiving antipsychotic treatment for early psychosis. Targeted
      interventions are therefore warranted from the onset of antipsychotic therapy.

PMID- 19398193
TI  - Carboxylated magnetic microbead-assisted fluoroimmunoassay for early biomarkers
      of acute myocardial infarction.
AB  - A carboxylated superparamagnetic microbead-assisted sandwich fluoroimmunoassay
      was successfully demonstrated for the analysis of the early protein markers,
      myoglobin and human heart-type fatty acid-binding protein (H-FABP), associated
      with acute myocardial infarction. This assay approach consisted of the
      preparation of superparamagnetic polymer microbeads using a dispersion
      polymerization, followed by grafting of capture antibodies (monoclonal anti-H
      FABP 10E1 and anti-myoglobin 7C3) onto the polymer microbeads using EDC-NHS
      protocol, and then a sequential sandwich fluoroimmunoassay using detection
      antibodies (FITC-labeled anti-H-FABP 9F3 and FITC-labeled anti-myoglobin 4E2).
      The Fe(3)O(4) nanoparticles and carboxylated Fe(3)O(4)-polymer microbeads were
      characterized by scanning electron microscopy, transmission electron microscopy,
      Fourier transform infrared spectrophotometry, vibrating sample magnetometry, and
      X-ray diffraction. The fluoroimmunoassay images were recorded using a confocal
      laser-scanning microscope, and the average fluorescence intensity of the
      microbeads was found to correspond to the concentration of each cardiac marker,
      in agreement with the results obtained by a spectrofluorophotometer. The
      carboxylated magnetic microbead-assisted protocol could be utilized to semi
      quantitatively detect both myoglobin and H-FABP.

PMID- 19398194
TI  - Effect of saturation degree on the interactions between fatty acids and
      phosphatidylcholines in binary and ternary Langmuir monolayers.
AB  - Fatty acids molecules have strong influence on membrane properties. In this work
      the interactions between fatty acids and phosphatidylcholines were studied in
      mixed binary and ternary Langmuir monolayers. The compounds investigated, both
      fatty acids and phospholipids were of the same hydrocarbon chain length and
      differed in their saturation degree (stearic acid (C18:0)), oleic acid (C18:1)),
      linoleic acid (C18:2) and distearoylphosphatidylcholine-DSPC and
      dioleoylphosphatidylcholine-DOPC). It was found that the investigated fatty acids
      interact more strongly with saturated phospholipid (DSPC) and more strongly
      affect the molecular organization of DSPC films as compared to DOPC monolayer.
      The saturated fatty acid (stearic acid) makes the phospholipid monolayers more
      rigid, while unsaturated fatty acids decrease the condensation of phospholipid
      films. The differences in the effect of the respective fatty acids on
      phosphatidylcholines monolayers were thoroughly analyzed from the point of view
      of geometry of the lipids molecules, which is determined by the saturation of the
      hydrocarbon chain.

PMID- 19398196
TI  - Properties of concrete blocks prepared with low grade recycled aggregates.
AB  - Low grade recycled aggregates obtained from a construction waste sorting facility
      were tested to assess the feasibility of using these in the production of
      concrete blocks. The characteristics of the sorted construction waste are
      significantly different from that of crushed concrete rubbles that are mostly
      derived from demolition waste streams. This is due to the presence of higher
      percentages of non-concrete components (e.g. >10% soil, brick, tiles etc.) in the
      sorted construction waste. In the study reported in this paper, three series of
      concrete block mixtures were prepared by using the low grade recycled aggregates
      to replace (i) natural coarse granite (10mm), and (ii) 0, 25, 50, 75 and 100%
      replacement levels of crushed stone fine (crushed natural granite <5mm) in the
      concrete blocks. Test results on properties such as density, compressive
      strength, transverse strength and drying shrinkage as well as strength reduction
      after exposure to 800 degrees C are presented below. The results show that the
      soil content in the recycled fine aggregate was an important factor in affecting
      the properties of the blocks produced and the mechanical strength deceased with
      increasing low grade recycled fine aggregate content. But the higher soil content
      in the recycled aggregates reduced the reduction of compressive strength of the
      blocks after exposure to high temperature due probably to the formation of a new
      crystalline phase. The results show that the low grade recycled aggregates
      obtained from the construction waste sorting facility has potential to be used as
      aggregates for making non-structural pre-cast concrete blocks.

PMID- 19398195
TI  - Indicators for steroid response in biopsy proven acute graft rejection after lung
      transplantation.
AB  - OBJECTIVE: Acute rejection (AR) after lung transplantation (LTx) requires prompt
      intervention. Most episodes respond to steroid pulse therapy. The aim of this
      study was to evaluate clinical indicators for non-response to steroid treatment
      in biopsy proven AR after the early postoperative period. METHODS: We
      prospectively analysed 85 patients more than 6 months after LTx with symptomatic
      biopsy proven AR (>or=grade A1) from Jan. 2005 until Nov. 2007 in a single
      centre. In 47 patients, AR was steroid-sensitive (group 1), 38 patients did not
      respond to steroid pulse therapy (group 2). All AR episodes were associated with
      clinical symptoms. Fifty-seven (67%) were low-grade rejections (ISHLT A1).
      RESULTS: Independent clinical predictors for steroid response vs. non-steroid
      response in biopsy proven AR were "days after transplantation" (p=0.01, adjusted
      hazard ratio (HR) 1.2), "decline in home spirometry slope" (p=0.03, HR 0.97),
      "adherence to home spirometry" (p=0.05, HR 0.98) and "serum CRP" (p=0.02, HR
      0.87). Eight patients (21%) of group 2 developed BOS during the following 6
      months. CONCLUSIONS: Early detection of deterioration in graft function seems to
      be crucial for effective treatment of AR. Home spirometry seems to be useful in
      detecting early changes in graft function and surveillance protocols could be
      potentially helpful in predicting patients likely to demonstrate a steroid
      response.

PMID- 19398197
TI  - Electrochemical sensor based on molecular imprinting by photo-sensitive polymers.
AB  - A novel voltammetric sensor based on molecularly imprinted polymers (MIPs) by a
      kind of photo-sensitive functional polymer was developed for determination of
      glucose in this work. Without the cross-linker and the initiator, a MIPs film on
      the surface of a gold electrode was easily formed by in-situ cross-link within 10
      min under UV light irradiation. In alkaline medium, electrochemical oxidation
      behaviors of glucose on the MIPs sensor, as well as on a bare gold electrode have
      been investigated with square wave voltammetry. At oxidation potential of -0.50 V
      (vs. SCE), the peak currents on the MIPs sensor were proportional to the
      concentration of glucose in the range of 5.0-120 microM with the detection limit
      of 0.2 microg ml(-1) (S/N=3), whereas the extremely small responses of the
      control electrode were observed and independent of the analyte concentration.
      MIPs sensor displayed specific selectivity toward glucose in comparison to
      structurally similar analogues. The selective coefficient of glucose MIPs sensor
      with respect to maltose, arabinose and mannose was 9.17, 1.51 and 1.25,
      respectively. Fructose and inositol would not interfere with the determination of
      glucose because they could not be electrochemically oxidized at the potential of 
      0.50 V. Relative rapid response of the MIPs sensor was obtained within 7 min, and
      the RSD of peak currents was 5.0% (n=5). MIPs sensor was applied to determine
      glucose in the simulative blood serum samples, the average recoveries was 92.6%.
      The experimental results showed that the sensor for glucose, based on MIPs by
      photo-sensitive polymers, was simpler to construct and operate, and provided an
      adequate sensitivity, good repeatability and accuracy and acceptable selectivity.

PMID- 19398198
TI  - Autotrophic denitrification using hydrogen generated from metallic iron
      corrosion.
AB  - Hydrogenotrophic denitrification was demonstrated using hydrogen generated from
      anoxic corrosion of metallic iron. For this purpose, a mixture of hydrogenated
      water and nitrate solution was used as reactor feed. A semi-batch reactor with
      nitrate loading of 2000 mg m(-3) d(-1) and hydraulic retention time (HRT) of 50
      days produced effluent with nitrate concentration of 0.27 mg N L(-1) (99% nitrate
      removal). A continuous flow reactor with nitrate loading of 28.9 mg m(-3) d(-1)
      and HRT of 15.6 days produced effluent with nitrate concentration of
      approximately 0.025 mg N L(-1) (95% nitrate removal). In both cases, the
      concentration of nitrate degradation by-products, viz., ammonia and nitrite, were
      below detection limits. The rate of denitrification in the reactors was
      controlled by hydrogen availability, and hence to operate such reactors at higher
      nitrate loading rates and/or lower HRT than reported in the present study,
      hydrogen concentration in the hydrogenated water must be significantly increased.

PMID- 19398199
TI  - Aryl sulfonamido tetralin inhibitors of the Kv1.5 ion channel.
AB  - Aryl sulfonamido tetralins based on lead compound 2a were synthesized and
      evaluated for Kv1.5 inhibitory activity. Several compounds having IC(50) values
      less then 0.1 microM were identified. Kv1.5 inhibitors have the potential to be
      atrium-selective agents for the treatment of atrial fibrillation.

PMID- 19398200
TI  - Optimization of benzimidazole series as opioid receptor-like 1 (ORL1)
      antagonists: SAR study directed toward improvement of selectivity over hERG
      activity.
AB  - A structure-activity relationship (SAR) study on the benzimidazole series of
      opioid receptor-like 1 (ORL1) antagonists related to 1 is described. Optimization
      of 1 by introduction of a hydrophilic substituent into the thioether part
      resulted in identification of potent ORL1 antagonists with high selectivity over
      binding affinity for hERG and other opioid receptors.

PMID- 19398201
TI  - One plasmid selection system for the rapid evolution of aminoacyl-tRNA
      synthetases.
AB  - We have developed a rapid, straightforward, one plasmid dual positive/negative
      selection system for the evolution of aminoacyl-tRNA synthetases with altered
      specificities in Escherichia coli. This system utilizes an amber stop codon
      containing chloramphenicol acetyltransferase/uracil phosphoribosyltransferase
      fusion gene. We demonstrate the utility of the system by identifying a variant of
      the Methanococcus jannaschii tyrosyl synthetase from a library of 10(9) variants
      that selectively incorporates para-iodophenylalanine in response to an amber stop
      codon.

PMID- 19398202
TI  - Asymmetric synthesis of beta,gamma-unsaturated alpha-amino acids via efficient
      kinetic resolution with cinchona alkaloids.
AB  - The beta,gamma-unsaturated amino acids are versatile chiral building blocks and
      biologically interesting compounds. The asymmetric synthesis of beta,gamma
      unsaturated amino acids presents a challenging task as these compounds are labile
      toward racemization as well as the undesirable double bond isomerization. An
      efficient, general and mild kinetic resolution with readily accessible and fully
      recyclable cinchona alkaloid catalysts has been developed to provide a reliably
      useful approach toward optically active beta,gamma-unsaturated amino acids.

PMID- 19398203
TI  - Evaluation of an electrolyte replacement protocol in an adult intensive care
      unit: a retrospective before and after analysis.
AB  - BACKGROUND: Electrolyte imbalances are frequently encountered in the Intensive
      Care Unit (ICU) and protocol-driven interventions may facilitate more timely and
      uniform care. OBJECTIVE: To compare the effectiveness and timeliness of
      electrolyte replacement in an adult ICU before and after implementation of an
      Electrolyte Replacement Protocol (ERP) and to assess nurse and physician
      satisfaction with the ERP. METHODS: Health records of adult patients who
      experienced hypokalaemia, hypomagnesaemia, or hypophosphataemia in the ICU during
      the study periods were retrospectively reviewed. Effectiveness of the ERP was
      assessed by the number of replacement doses indicated but not given and the
      number of doses and total dose required to normalise the low electrolyte level.
      Timeliness was evaluated by the time between the laboratory reporting the low
      electrolyte level and administration of the replacement dose. Nurse and physician
      satisfaction with the ERP was assessed through a written survey. RESULTS: After
      implementation of the ERP, the number of replacement doses indicated but not
      given was reduced for magnesium from 60% to 35% (p=0.18) and for phosphate from
      100% to 64% (p=0.04). The time to replacement was reduced for potassium from 79
      to 60 min (p=0.066) and for magnesium from 307 to 151 min (p=0.15). Nurses and
      physicians were satisfied with the ERP. CONCLUSIONS: Implementation of an ERP
      resulted in improvements in the effectiveness and timeliness of electrolyte
      replacement and nurses and physicians were satisfied with the ERP.

PMID- 19398204
TI  - Synthesis and evaluation of pharmacological profile of 1-aryl-6,7-dimethoxy-3,4
      dihydroisoquinoline-2(1H)-sulfonamides.
AB  - In previous studies we identified several 1-aryl-6,7-dimethoxy-1,2,3,4
      tetrahydroisoquinoline derivatives displaying potent anticonvulsant effects in
      different animal models of epilepsy. With the aim to deepen the structure
      activity relationships (SAR) for this class of compounds and identify novel
      anticonvulsant agents we synthesized a series of 1-aryl-6,7-dimethoxy-3,4
      dihydroisoquinoline-2(1H)-sulfonamides. The new compounds incorporate the main
      features of the above-mentioned anticonvulsants and a sulfonamide function
      capable to inhibit the enzyme carbonic anhydrase (CA, EC 4.2.1.1), which
      represents an attractive target in epilepsy. Pharmacological effects were
      evaluated in vivo against audiogenic seizures in DBA/2 mice and in vitro against
      several CA isoforms. Some of the new molecules showed anticonvulsant properties
      better than topiramate, but weak inhibitory activity and low selectivity in
      enzymatic assay.

PMID- 19398205
TI  - Design, synthesis, and biological evaluation of novel diarylalkyl amides as TRPV1
      antagonists.
AB  - We have developed a new class of diarylalkyl amides as novel TRPV1 antagonists.
      They exhibited potent (45)Ca(2+) uptake inhibitions in rat DRG neuron. In
      particular, the amide 59 was identified as a potent antagonist with IC(50) of 57
      nM. The synthesis and structure-activity relationship of the diarylalkyl amides
      are also described.

PMID- 19398206
TI  - Mechanism of action of N-phenyl-N'-(2-chloroethyl)ureas in the colchicine-binding
      site at the interface between alpha- and beta-tubulin.
AB  - Computational tools such as CoMSIA and CoMFA models reported in a recent study
      revealed the structure-activity relationships ruling the interactions occurring
      between hydrophobic N-phenyl-N'-(2-chloroethyl)ureas (CEU) and the colchicine
      binding site (C-BS) on beta(II)-tubulin. Here, we describe the mechanisms
      involved in the covalent binding of three subsets of CEU derivatives to the C-BS.
      The FlexiDock experiments confirmed that the interaction of non-covalent portions
      of the CEU auxophore moiety of CEU is involved in the binding of the drug to the
      C-BS facilitate the nucleophilic attack of Glu-beta198 rather than Cys-beta239.
      In addition, these studies suggest that Cys-beta239 together with Asn-alpha99,
      Ser-alpha176, Thr-alpha177, Leu-beta246, Asn-beta247, Ala-beta248, Lys-beta252
      and Asn-beta256 are implicated in the stabilization of a C-BS-CEU complex prior
      to the acylation of Glu-beta198 by CEU. Our molecular models propose the
      formation of a stabilized C-BS-CEU complex before the completion of the Glu
      beta198 acylation; acylation triggering conformational changes of beta-tubulin,
      microtubule depolymerization and anoikis. The computational models presented here
      might be useful to the design of selective and more potent C-BS inhibitors. Of
      interest, in vivo acylation of acidic amino acid residues by xenobiotics is an
      unusual reaction and may open new approaches for the design of irreversible
      protein inhibitors such as tubulin.

PMID- 19398207
TI  - QSAR models for predicting enzymatic hydrolysis of new chemical entities in 'soft
      drug' design.
AB  - The work described here is aimed at developing QSAR models capable of predicting
      in vitro human plasma lability/stability. They were built based on a dataset
      comprising about 200 known compounds. 3D structures of the molecules were drawn,
      optimized and submitted to the calculation of molecular descriptors that enabled
      selecting different TR/TS set pairs, subsequently exploited to develop QSAR
      models. Several 'machine learning' algorithms were explored in order to obtain
      suitable classification models, which were then validated on the relevant TS
      sets. Moreover the predictive ability of the best performing models was assessed
      on a Prediction set (PS) comprising about 40 molecules, not strictly related,
      from a structural point of view, to the initial dataset, but (obviously)
      comprised within the validity domain of the QSAR models obtained. The study
      allowed selecting predictive models enabling the classification of New Chemical
      Entities with regard to hydrolysis rate, that may be exploited for soft-drug
      design.

PMID- 19398208
TI  - Up-regulation of TNF-alpha in neurons of dorsal root ganglia and spinal cord
      during coronary artery occlusion in rats.
AB  - Knowledge about the physiologic and pathophysiologic roles of tumor necrosis
      factor-alpha (TNF-alpha) in acute myocardial ischemia/infarction is still very
      limited. Evidence implies that TNF-alpha is involved in neural activity including
      nociception in peripheral and central nervous system. Current study was designed
      to examine the association of change in TNF-alpha and its mRNA in upper thoracic
      dorsal root ganglia and spinal cord (T1-T5) during acute myocardial
      ischemia/infarction induced by coronary artery occlusion (CAO) in rats. The
      experiment was performed using immunohistochemistry, enzyme immunoassay, in situ
      hybridization and real time reverse transcription-polymerase chain reaction
      techniques. At 0.5h, 1h, 3h and 6h of acute myocardial ischemia/infarction, TNF
      alpha was mainly up-regulated in a sub-population of small and medium neurons and
      satellite cells in the dorsal root ganglia (DRG) and spinal neurons, mainly in
      laminae I, II and V, VI of the spinal dorsal horn of upper thoracic segments. The
      up-regulation of TNF-alpha mRNA was observed at 30min of CAO, which was
      statistically significant, compared with the control and the sham surgery groups
      (P<0.01). The TNF-alpha mRNA was located in the satellite cells and afferent
      neurons of the DRG and spinal neurons, located mainly in laminae II-VI. The
      findings indicate an association of up-regulation of TNF-alpha in DRG and spinal
      cord with acute myocardial ischemia/infarction, suggesting that TNF-alpha may be
      associated with the nociception initiated by acute myocardial
      ischemia/infarction, while the pathophysiological role needs to be studied.

PMID- 19398209
TI  - Tail biting induces a strong acute phase response and tail-end inflammation in
      finishing pigs.
AB  - The extent of inflammation associated with tail biting in finishing pigs was
      evaluated. Tail histopathology, carcass condemnation and the concentration of
      three acute phase proteins (APPs), C-reactive protein (CRP), serum amyloid-A
      (SAA) and haptoglobin (Hp), were examined in 12 tail-bitten and 13 control pigs.
      The median concentrations of APPs were higher (P<0.01) in bitten (CRP 617.5mg/L,
      range 80.5-969.9; SAA 128.0mg/L, 6.2-774.4; Hp 2.8g/L, 1.6-3.5) than in control
      pigs (CRP 65.7mg/L, 28.4-180.4; SAA 6.2mg/L, 6.2-21.4; Hp 1.2g/L, 0.9-1.5). There
      was a tendency for APP concentrations to rise with the histopathological score
      but the differences were only statistically significant between some of the
      scores. Five (42%) bitten cases and one (8%) control pig had partial carcass
      condemnations owing to abscesses (P=0.07). The results show that tail biting
      induces an inflammatory response in the tail end leading to an acute phase
      response and formation of carcass abscesses.

PMID- 19398210
TI  - Compartment shape anisotropy (CSA) revealed by double pulsed field gradient MR.
AB  - The multiple scattering extensions of the pulsed field gradient (PFG) experiments
      can be used to characterize restriction-induced anisotropy at different length
      scales. In double-PFG acquisitions that involve two pairs of diffusion gradient
      pulses, the dependence of the MR signal attenuation on the angle between the two
      gradients is a signature of restriction that can be observed even at low gradient
      strengths. In this article, a comprehensive theoretical treatment of the double
      PFG observation of restricted diffusion is presented. In the first part of the
      article, the problem is treated for arbitrarily shaped pores under idealized
      experimental conditions, comprising infinitesimally narrow gradient pulses with
      long separation times and long or vanishing mixing times. New insights are
      obtained when the treatment is applied to simple pore shapes of spheres,
      ellipsoids, and capped cylinders. The capped cylinder geometry is considered in
      the second part of the article where the solution for a double-PFG experiment
      with arbitrary experimental parameters is introduced. Although compartment shape
      anisotropy (CSA) is emphasized here, the findings of this article can be used in
      gleaning the volume, eccentricity, and orientation distribution function
      associated with ensembles of anisotropic compartments using double-PFG
      acquisitions with arbitrary experimental parameters.

PMID- 19398211
TI  - Plasma insulin-like growth factor I as predictor of progression and all cause
      mortality in chronic heart failure.
AB  - OBJECTIVES: Insulin-like growth factor I (IGF-I) is an anabolic growth factor
      that seems to increase cardiac contractility. Reduced levels of IGF-I may be
      implicated in progression of CHF. The objective was to compare plasma IGF-I in
      CHF patients with healthy controls, and to examine the associations between
      baseline IGF-I levels, cardiac contractility and the prognosis as judged by all
      cause mortality and progression of CHF requiring admission to hospital. METHODS:
      A prospective study comprising 194 CHF outpatients, and 169 matched controls. All
      patients and controls underwent echocardiographic examination at baseline.
      Patients were followed for a median of 30 months. RESULTS: There was no
      difference in IGF-I levels between patients and controls (median and
      interquartile range), 78 (58-91) vs. 77 (57-94)ng/mL (P=0.92). Age-adjusted IGF-I
      levels were not related to left ventricular ejection fraction (LVEF) (P=0.58) or
      levels of N-terminal B-Type natriuretic peptide (NT-proBNP) (P=0.42). During
      follow-up 44 patients died and 94 were admitted to hospital due to worsening of
      CHF. Adjusted for cardiovascular risk factors (age, gender, NT-proBNP, lipids,
      diabetes mellitus, blood pressure, renal function and LVEF) IGF-I levels did not
      influence the overall mortality risk or the admission rate to hospital, hazard
      ratio (HR) (95% confidence intervals) 1.05 (0.75-1.47) (P=0.77) and 1.00 (0.80
      1.26) (P=0.96), respectively per each SD increase in log IGF-I levels.
      CONCLUSIONS: IGF-I levels were not reduced in patients with CHF and did not
      influence cardiac status at baseline or the prognosis.

PMID- 19398213
TI  - Bacteremia due to Clostridium difficile--review of the literature.
AB  - Extracolonic Clostridium difficile infections have been infrequently reported.
      Extracolonic manifestations of C. difficile include bacteremia, intra-abdominal
      abscess, osteomyelitis, visceral abscess, empyema, reactive arthritis, and small
      bowel disease with formation of pseudomembranes on ileal mucosa. Most cases of
      extracolonic C. difficile have been preceded by gastrointestinal disease, either
      C. difficile colitis or surgical and anatomical disruption of the colon.
      Bacteremia due to C. difficile has previously been described in 14 patients with
      underlying gastrointestinal processes. We report a unique case of monomicrobial
      C. difficile bacteremia in a young woman with an underlying hematologic
      malignancy. The patient lacked gastrointestinal symptoms or radiologic findings
      suggestive of colitis or ongoing gastrointestinal pathology.

PMID- 19398214
TI  - Facial bullous cellulitis caused by acute sinusitis.

PMID- 19398212
TI  - Hermansky-Pudlak syndrome type 1 in patients of Indian descent.
AB  - Hermansky-Pudlak syndrome (HPS) develops from defects in the biogenesis and/or
      function of lysosome-related organelles essential to membrane and protein
      trafficking. Of the eight known human subtypes, only HPS-1 and HPS-4 develop
      pulmonary fibrosis in addition to the general clinical manifestations of
      oculocutaneous albinism and bleeding diathesis. We identified HPS-1 in three
      unrelated patients from different regions of India, who presented with iris
      transillumination, pale fundi, hypopigmentation, nystagmus, decreased visual
      acuity, and a bleeding diathesis. Two of these patients carried the homozygous
      mutation c.398+5G>A (IVS5+5G>A) in HPS1, resulting in skipping of exon 5 in HPS1
      mRNA. The third patient carried a novel homozygous c.988-1G>T mutation that
      resulted in in-frame skipping of HPS1 exon 12 and removes 56 amino acids from the
      HPS1 protein. Given the discovery of HPS-1 in an ethnic group where
      oculocutaneous albinism (OCA) is highly prevalent, it is possible that HPS in
      India is under-diagnosed. We recommend that unconfirmed OCA patients in this
      ethic group be considered for mutational screening of known HPS genes, in
      particular c.398+5G>A and c.980-1G>T, to ensure that patients can be monitored
      and treated for clinical complications unique to HPS.

PMID- 19398215
TI  - The role of rehabilitation in deep brain stimulation of the subthalamic nucleus
      for Parkinson's disease: a pilot study.
AB  - Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an
      efficacious therapeutic option in the treatment of advanced Parkinson's disease
      (PD). The procedure may be however associated with functional impairment of
      different types and intensity. In this paper we describe the functional
      impairments detected in a group of 34 subjects with PD who were submitted to DBS.
      These patients belonged to a cohort of 75 consecutive PD patients who underwent
      the surgical procedure. The rehabilitation program included physiotherapy
      exercises for recovery/maintenance of the range of motion, active exercises,
      exercises for coordination and proprioception, and walking training based on the
      use of sensory cues, with daily sessions for a period of 4-8 weeks. The motor
      examination section of unified Parkinson's disease rating scale (UPDRS-ME) and
      the functional independence measure (FIM) scores showed a consistent and
      significant improvement in the patients' motor performances. The reported
      findings suggest that rehabilitation may play an important role in the correction
      of specific functional impairments caused by or associated with DBS in PD.

PMID- 19398216
TI  - Low-risk human papillomavirus type 6 DNA load and integration in cervical samples
      from women with squamous intraepithelial lesions.
AB  - BACKGROUND: The association between human papillomavirus (HPV) viral load and
      high-grade squamous intraepithelial lesion (HSIL) of the uterine cervix has been
      demonstrated for high-risk HPV-16 but has not been investigated for low-risk HPV
      types. OBJECTIVE: To determine the association between the presence of low-grade
      SIL (LSIL) and viral load of low-risk HPV type 6. STUDY DESIGN: 107 HPV-6
      positive cytobrush samples collected from 90 women (67 without SIL, 11 with LSIL,
      5 with HSIL, 6 with SIL of unknown grade and 1 with a smear with LSIL and a
      normal colposcopy) were analyzed for their content of HPV-6 DNA. METHODS: HPV-6
      E6 and E2 DNA loads were measured in the cytobrush samples with two real-time PCR
      assays. HPV-6 integration was confirmed with restriction-site PCR. RESULTS: HPV-6
      DNA in cervical samples ranged from 1.8 x 10(2) to 4.25 x 10(8) copies per microg
      of cellular DNA. HPV-6 E6 DNA loads were higher in women with LSIL, with or
      without co-infection with high-risk HPV types, than in women without SIL
      (p=0.03). HPV-6 loads greater than 8.76 x 10(6)copies per microgDNA,
      corresponding to the mean HPV-6 load measured in women with LSIL, were more
      frequently detected in these women with LSIL than in women without LSIL,
      controlling for age (odds ratio 13.5, 95% confidence interval 1.1-172.4).
      Although 10 samples generated HPV-6 E6/E2 ratios above 2, there was no evidence
      of integration of HPV-6 by restriction-site PCR. CONCLUSION: Samples from women
      with LSIL contained higher HPV-6 loads than women without SIL. HPV-6 DNA was not
      integrated into cellular DNA in these samples.

PMID- 19398217
TI  - Development, validity, and reliability of The Assessment of Pain and Occupational
      Performance (POP): a new instrument using two dimensions in the investigation of
      disability in back pain.
AB  - BACKGROUND CONTENT: Questionnaires for measuring the functional status of
      patients with low back pain (LBP) focus on disability and present responses for
      each question in a predetermined, fixed relationship between "can do/difficulties
      and pain." Their design does not permit a separation of the two. PURPOSE: To
      present the development of The Assessment of Pain and Occupational Performance
      (POP) and to evaluate validity and reliability. STUDY DESIGN: A prospective,
      consecutive study of patients investigated by use of the POP. PATIENT SAMPLE: A
      total of 220 patients participated in the study. METHODS: In a cross-sectional
      study including 53 patients with chronic musculoskeletal pain, empirical tests of
      content and construct validity established the definitive version of the POP. The
      POP focuses on performance of activities. It is a disease-specific,
      discriminative assessment instrument designed for patients with back pain (BP)
      and LBP. Based on a semi-structured interview the POP investigates each of 36
      activities in two dimensions, with separate, defined scales from "normally
      healthy" to "extremes" for level of activity (x-scale) and pain intensity (y
      scale). The final scores are expressed in percent, 0% to 100%. Patients with
      chronic LBP (CLBP) (n=142) were allocated to the specific (S) group, that is,
      patients with specific LBP problems (n=97) or to the nonspecific (NS) group, that
      is, those with NS BP (n=45). The ability of the POP to differentiate between the
      two known groups was evaluated. Construct-convergent validity between the POP and
      the Oswestry Disability Index (ODI) was carried out for the S group. Inter-rater
      reliability was established between six pairs of raters who examined 25 patients
      recruited from primary health care, the P-LBP group. RESULTS: In construct known
      group validity, the median, the interquartile range, and the Mann-Whitney U test
      showed that the S group had a significantly higher level of activity (p<.001)
      combined with worse pain (p=.001) compared with the NS group. There were
      significant differences between the two groups in performing activities in the
      forward bending position (10 items) and in the upright standing position (9
      items). The result of Spearman rank order correlation showed a strong
      relationship between the ODI and the POP for level of activity (r=0.70,
      p<or=.001). The multiple correlation coefficient between the total score of the
      ODI (10 items) and the total score of the POP (36 items) was r=0.72 and
      p<or=.001. Inter-rater reliability-the standard deviation of the differences was
      less than 1 point (scale 0-5). A Bland-Altman plot showed the mean differences
      for the level of activity of the dressing/undressing item. The average percentage
      agreement was 80% on the x- and y-scales. In POP 36, the average Kappa for level
      of activity was 0.79, which is good agreement, and for pain 0.84, which is very
      good agreement. CONCLUSION: The construction of the POP allows the patient to
      count, and the occupational therapist to investigate, from full level of activity
      to avoidance and from no pain to worst imaginable pain for each physically loaded
      task in personal activities of daily living (ADL), transfer/transport,
      instrumental ADL, and social activities. The POP can differentiate between groups
      concerning level of activity and pain, and appears to be a valid and reliable
      instrument for evaluating LBP. The POP should be considered for use in both
      clinical and research applications.

PMID- 19398218
TI  - Elimination of diastereomer interference to determine Telcagepant (MK-0974) in
      human plasma using on-line turbulent-flow technology and off-line solid-phase
      extraction coupled with liquid chromatography/tandem mass spectrometry.
AB  - To eliminate the diastereomer interference on Telcagepant (MK-0974) determination
      during clinical study support, on-line high turbulent-flow liquid chromatography
      (HTLC) methods, HTLC-A and HTLC-B that covered dynamic range of 0.5-500 nM and 5
      5000 nM, respectively, were developed. To meet the requirement of rapid assay
      transfer among multiple laboratories and analysts, a solid-phase extraction (SPE)
      assay was derived from the existing HTLC-B assay under the same dynamic range.
      The on-line HTLC assays were achieved through direct injection of plasma samples,
      extraction of analyte with a Cohesive C18 column (50 mm x 0.5 mm, 50 microm),
      followed by HPLC separation on a FluoPhase RP column (100 mm x 2.1 mm, 5 microm)
      and MS/MS detection. The off-line SPE assay used Waters Oasis HLB microElution
      plate to extract the analytes from plasma matrix before injecting on a FluoPhase
      RP column (150 mm x 2.1 mm, 5 microm) for LC-MS/MS analysis. Under both on-line
      and off-line assay conditions, the diastereomer 1c was chromatographically
      separated from MK-0974. Cross-validation with the pooled samples demonstrated
      that both on-line and off-line assays provided comparable data with a difference
      of < 2.6%. The assays were proved to be specific, accurate and reliable, and have
      been used to support multiple clinical studies. The pros and cons of on-line and
      off-line assays with regard to man power involved in sample preparation, total
      analysis time, carryover, cost efficiency, and the requirement for assay transfer
      are discussed.

PMID- 19398219
TI  - Expression and purification of soluble E-Syt2: low protein stability impedes tag
      removal.
AB  - Affinity tags are valuable tools for high-throughput protein isolation in
      automated screenings or downstream processing approaches and are also widely used
      in laboratory applications for quick and easy access to many proteins. Here, we
      describe the preparative purification of soluble extended synaptotagmin 2 (rE
      Syt2) at bench scale for basic structural and functional studies. Due to the low
      protein stability, a classical purification procedure without affinity tag was
      more powerful than isolation of His((6))-tagged rE-Syt2 and subsequent
      proteolytic tag-removal. Furthermore, expression analysis of truncated rE-Syt2
      variants suggested a concept of interdependent-domain organization in proteins
      containing multiple C2 domains.

PMID- 19398220
TI  - An interview with Alexander Eggermont.

PMID- 19398221
TI  - Laser-assisted Zr/ZrO(2) coating on Ti for load-bearing implants.
AB  - Oxidized Zr alloys have been shown to exhibit lower friction and superior wear
      properties, suggesting that they could be used in hip and knee implants. However,
      conventional oxidation of Zr alloys above 500 degrees C, in dry air, for several
      hours has been shown to have detrimental effects on the substrate's properties.
      In this work, we deposited pure Zr on Ti, then oxidized the coating using a
      continuous-wave Nd:YAG laser, which facilitated localized heating to elevated
      temperatures without affecting the substrate. Laser-assisted oxidation resulted
      in a 7microm thick fully dense ZrO(2) layer on Zr in which an increase in
      oxidation kinetics was evident due to an increase in the laser power and/or the
      oxygen partial pressure. Due to its high surface energy and wettability, the wear
      rate of laser-oxidized Zr was two orders of magnitude less compared to that of as
      deposited Zr. The oxidized coatings showed comparable in vitro biocompatibility
      to that of pure Ti and excellent in vitro cell-material interactions. This
      article reports the processing of Zr/ZrO(2) coatings on Ti using lasers, and the
      influence of laser parameters and oxygen partial pressure on the coating's
      mechanical, microstructural, wear and in vitro biological properties using human
      osteoblast cells.

PMID- 19398222
TI  - Treatment of giant congenital melanocytic nevi with enzymatically separated
      epidermal sheet grafting.
AB  - Treatment of giant congenital melanocytic nevi (GCMNs) must be considered from
      both a cosmetic and a medical aspect of reducing the risk of a growing
      malignancy. We treated five patients who had a GCMN on the trunk with an
      enzymatically separated epidermal sheet taken from their excised GCMN skin. All
      patients underwent enzymatically separated epidermal sheet grafting at the age of
      2 months. With the patient under general anaesthesia, we removed the affected
      area with an electric dermatome until the brown colour had almost completely
      disappeared. The removed skin was immersed in dispase I solution (1000Uml(-1))
      dissolved in Ringer's solution at 37 degrees C for 75-105min until the epidermal
      sheet separated from the dermis without tension. Three back lesions and two
      abdominal lesions were treated. In all cases, the enzymatically separated
      epidermis grafted well, without infection. The amount of discharge that
      accumulated from immediately after the operation until the first dressing change
      (performed at 3 days after the operation) was reduced compared with that from
      curettage. The skin colour was light brown at first and gradually became lighter
      within a few months. The grafted areas were soft and did not show significant re
      pigmentation. In most cases, hard hair did not grow on the treated area.
      Histological samples taken 1 year after the operation showed that the dermal
      layer was reconstituted without pigmented nevus cells. Enzymatically separated
      epidermal grafting is a useful method for the treatment of GCMN, is easy to
      perform and leaves cosmetically satisfactory results.

PMID- 19398223
TI  - Surgical management of hidradenitis suppurativa in the sub-mammary area.

PMID- 19398224
TI  - Post-traumatic fronto-ethmoid osteomyelitis treated with free muscle transfer.
AB  - Intractable frontal sinus infection after obliteration of the injured sinus and
      nasofrontal duct has become a less common injury nowadays. Adequate debridement
      complemented with a viable peri-cranial flap would usually prevent the
      troublesome frontal sinusitis. Nonetheless if recurrent infection involves both
      the frontal and ethmoid sinuses, local tissues may not suffice for obliteration
      of the dead space. We developed the use of a free vascularised muscle flap that
      may be the best option in treating osteomyelitic sinusitis. Three cases of
      intractable fronto-ethmoid osteomyeltic sinusitis treated by free vascularised
      tissue transfer are reported in this article. The use of free muscle flaps not
      only sealed the dead spaces with sufficient volume of viable tissue but also
      introduced vascularity into a relatively avascular zone. Furthermore, the
      advantages of microsurgical transfer allowed, without limiting the size of the
      free flap, a more extensive debridement which was the prerequisite for successful
      control of an infection.

PMID- 19398225
TI  - Plasma concentrations of natriuretic peptides in normal cats and normotensive and
      hypertensive cats with chronic kidney disease.
AB  - OBJECTIVES: To determine if natriuretic peptide concentrations are increased in
      cats with systemic hypertension and/or chronic kidney disease (CKD). ANIMALS: 22
      normal cats, 13 normotensive cats with mild-moderate CKD (NT-CKD), 15
      hypertensive cats with mild-moderate CKD (HT-CKD) and 8 normotensive cats with
      severe CKD (NT-CKD-severe). METHODS: N-terminal pro-B-type (NT-proBNP) and pro-A
      type (NT-proANP) natriuretic peptides were measured in plasma samples from all
      cats using commercially available assays and concentrations in the normal and
      diseased groups compared using non-parametric statistical tests. Spearman's rank
      correlation was used to test for an association between natriuretic peptide and
      creatinine concentrations. RESULTS: NT-proANP was significantly higher in the NT
      CKD-severe than the normal group of cats (P=0.006) but there were no other
      differences between groups. NT-proBNP concentrations were significantly higher in
      the HT-CKD group than both the normal (P<0.001) and the NT-CKD (P<0.001) groups.
      NT-proBNP concentrations were also higher in the NT-CKD-severe (P<0.001) and the
      NT-CKD (P=0.005) groups than the normal group. NT-proANP but not NT-proBNP was
      significantly and positively associated with plasma creatinine concentration.
      CONCLUSIONS: Measurement of NT-proBNP shows promise as a diagnostic marker for
      systemic hypertension in the cat. Its concentration is not significantly
      increased in cats with mild-moderate normotensive CKD.

PMID- 19398226
TI  - Surface marker antigens in the characterization of human embryonic stem cells.
AB  - The use of cell surface antigens to characterise embryonic stem (ES) cells, and
      to monitor their differentiation, has had a long history, stretching back to the
      early studies of differentiation antigens in the haematopoietic system, and their
      application to teratocarcinomas and embryonal carcinoma (EC) cells in the
      laboratory mouse. A wide series of such antigens, which include both glycolipids
      and glycoproteins are now extensively used in studies of human ES cells. Many of
      these were first identified using both mouse and human EC cells, although the
      cell surface antigen phenotype of human EC and ES cells has proved to be
      significantly different from that of murine EC and ES cells.

PMID- 19398227
TI  - PPARdelta agonist attenuates alcohol-induced hepatic insulin resistance and
      improves liver injury and repair.
AB  - BACKGROUND/AIMS: Chronic ethanol exposure impairs liver regeneration due to
      inhibition of insulin signaling and oxidative injury. PPAR agonists function as
      insulin sensitizers and anti-inflammatory agents. We investigated whether
      treatment with a PPARdelta agonist could restore hepatic insulin sensitivity,
      survival signaling, and regenerative responses vis-a-vis chronic ethanol feeding.
      METHODS: Adult rats were fed isocaloric liquid diets containing 0% or 37%
      ethanol, and administered a PPARdelta agonist by i.p. injection. We used liver
      tissue to examine histopathology, gene expression, oxidative stress, insulin
      signaling, and regenerative responses to 2/3 hepatectomy. RESULTS: Chronic
      ethanol feeding caused insulin resistance, increased oxidative stress, lipid
      peroxidation, DNA damage, and hepatocellular injury in liver. These effects were
      associated with reduced insulin receptor binding and affinity, impaired survival
      signaling through PI3K/Akt/GSK3beta, and reduced expression of insulin responsive
      genes mediating energy metabolism and tissue remodeling. PPARdelta agonist
      treatment reduced ethanol-mediated hepatic injury, oxidative stress, lipid
      peroxidation, and insulin resistance, increased signaling through
      PI3K/Akt/GSK3beta, and enhanced the regenerative response to partial hepatectomy.
      CONCLUSIONS: PPARdelta agonist administration may attenuate the severity of
      chronic ethanol-induced liver injury and ethanol's adverse effects on the hepatic
      repair by restoring insulin responsiveness, even in the context of continued high
      level ethanol consumption.

PMID- 19398229
TI  - HALT-C in the final analysis: a molehill out of a mountain.

PMID- 19398228
TI  - Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic
      effects on human hepatic stellate cells.
AB  - BACKGROUND/AIMS: Hepatic fibrogenesis, a consequence of chronic liver tissue
      damage, is characterized by activation of the hepatic stellate cells (HSC).
      Silybin has been shown to exert anti-fibrogenic effects in animal models.
      However, scant information is available on the fine cellular and molecular events
      responsible for this effect. The aim of this study was to assess the mechanisms
      regulating the anti-fibrogenic and anti-inflammatory activity of Silybin.
      METHODS: Experiments were performed on HSC isolated from human liver and
      activated by culture on plastic. RESULTS: Silybin was able to inhibit dose
      dependently (25-50 microM) growth factor-induced pro-fibrogenic actions of
      activated human HSC, including cell proliferation (P < 0.001), cell motility (P <
      0.001), and de novo synthesis of extracellular matrix components (P < 0.05).
      Silybin (25-50 microM), inhibited the IL-1-induced synthesis of MCP-1 (P < 0.01)
      and IL-8 (P < 0.01) showing a potent anti-inflammatory activity. Silybin exerts
      its effects by directly inhibiting the ERK, MEK and Raf phosphorylation, reducing
      the activation of NHE1 (Na+/H+ exchanger, P < 0.05) and the IkBalpha
      phosphorylation. In addition, Silybin was confirmed to act as a potent anti
      oxidant agent. CONCLUSION: The results of the study provide molecular insights
      into the potential therapeutic action of Silybin in chronic liver disease. This
      action seems to be mostly related to a marked inhibition of the production of pro
      inflammatory cytokines, a clear anti-oxidant effect and a reduction of the direct
      and indirect pro-fibrogenic potential of HSC.

PMID- 19398230
TI  - Unsaturated fatty acids promote hepatoma proliferation and progression through
      downregulation of the tumor suppressor PTEN.
AB  - BACKGROUND/AIMS: The impact of dietary fatty acids on the development of cancers
      is highly controversial. We recently demonstrated that unsaturated fatty acids
      trigger the downregulation of the tumor suppressor PTEN through an mTOR/NF-kappaB
      dependent mechanism in hepatocytes. In this study, we investigated whether
      unsaturated fatty acids promote hepatoma progression by downregulating PTEN
      expression. METHODS: The effects of fatty acids and PTEN-specific siRNAs on
      proliferation, invasiveness and gene expression were assessed using HepG2
      hepatoma cells. The tumor promoting activity of unsaturated fatty acids was
      evaluated in vivo using HepG2 xenografts in nude mice. RESULTS: Incubation of
      HepG2 cells with unsaturated fatty acids, or PTEN-specific siRNAs, increased cell
      proliferation, cell migration and invasiveness, and altered the expression of
      genes involved in inflammation, epithelial-to-mesenchymal transition and
      carcinogenesis. These effects were dependent on PTEN expression levels and were
      prevented by mTOR and NF-kappaB inhibitors. Consistent with these data, the
      development and size of subcutaneous HepG2-derived tumors in nude mice xenografts
      were dramatically increased when mice were fed with an oleic acid-enriched diet,
      even in the absence of weight gain. CONCLUSIONS: These data demonstrate that
      dietary unsaturated fatty acids promote hepatoma progression by reducing the
      expression of the tumor suppressor PTEN.

PMID- 19398231
TI  - Ethanol-induced liver injury and changes in sulfur amino acid metabolomics in
      glutathione peroxidase and catalase double knockout mice.
AB  - BACKGROUND/AIMS: Oxidative stress via generation of reactive oxygen species is
      suggested to be the major mechanism of alcohol-induced liver injury. We
      investigated the effects of glutathione peroxidase-1 and catalase double
      deficiency (Gpx-1(-/-)/Cat(-/-)) on liver injury and changes in the sulfur amino
      acid metabolism induced by binge ethanol administration. METHODS: Ethanol (5
      g/kg) was administered orally to the wild-type and the Gpx-1(-/-)/Cat(-/-) mice
      every 12 h for a total of three doses. Mice were sacrificed 6 h after the final
      dose. RESULTS: The Gpx-1/Cat deficiency alone increased malondialdehyde levels in
      liver significantly. Hepatic methionine adenosyltransferase (MAT) activity and S
      adenosylmethionine levels were decreased, however, glutathione contents were not
      changed. Ethanol administration to the Gpx-1(-/-)/Cat(-/-) mice increased the
      elevation of serum alanine aminotransferase activity, plasma homocysteine levels,
      hepatic fat accumulation and lipid peroxidation compared with the wild-type
      animals challenged with ethanol. Also the reduction of MAT activity and S
      adenosylmethionine levels was enhanced, but MATI/III expression was increased
      significantly. CONCLUSIONS: The results indicate that Gpx-1 and Cat have critical
      roles in the protection of liver against binge ethanol exposure. Augmentation of
      ethanol-induced oxidative stress may be responsible for the impairment of the
      transsulfuration reactions and the aggravation of acute liver injury in the Gpx
      1(-/-)/Cat(-/-) mice.

PMID- 19398232
TI  - Vitamin D receptor polymorphisms in primary biliary cirrhosis: a functional
      connection?

PMID- 19398233
TI  - Polyenephosphatidylcholine prevents alcoholic liver disease in PPARalpha-null
      mice through attenuation of increases in oxidative stress.
AB  - BACKGROUND/AIMS: Alcoholic liver disease (ALD) is one of the leading causes of
      cirrhosis and yet efficient therapeutic strategies are lacking.
      Polyenephosphatidylcholine (PPC), a major component of essential phospholipids,
      prevented alcoholic liver fibrosis in baboons, but its precise mechanism remains
      uncertain. We aimed to explore the effects of PPC on ALD using ethanol-fed
      peroxisome proliferator-activated receptor alpha (Ppara)-null mice, showing
      several similarities to human ALD. METHODS: Male wild-type and Ppara-null mice
      were pair-fed a Lieber-DeCarli control or 4% ethanol-containing diet with or
      without PPC (30 mg/kg/day) for 6 months. RESULTS: PPC significantly ameliorated
      ethanol-induced hepatocyte damage and hepatitis in Ppara-null mice. These effects
      were likely a consequence of decreased oxidative stress through down-regulation
      of reactive oxygen species (ROS)-generating enzymes, including cytochrome P450
      2E1, acyl-CoA oxidase, and NADPH oxidases, in addition to restoration of
      increases in Toll-like receptor 4 and CD14. PPC also decreased Bax and truncated
      Bid, thus inhibiting apoptosis. Furthermore, PPC suppressed increases in
      transforming growth factor-beta1 expression and hepatic stellate cell activation,
      which retarded hepatic fibrogenesis. CONCLUSIONS: PPC exhibited anti
      inflammatory, anti-apoptotic, and anti-fibrotic effects on ALD as a result of
      inhibition of the overexpression of ROS-generating enzymes. Our results
      demonstrate detailed molecular mechanisms of the anti-oxidant action of PPC.

PMID- 19398234
TI  - Performance of 11 biomarkers for liver fibrosis assessment in HIV/HBV co-infected
      patients.
AB  - BACKGROUND/AIMS: The aim of this study was to compare the performance of 11
      biochemical scores to estimate liver fibrosis in HIV/HBV co-infection. METHODS:
      Performance was evaluated using the Receiver Operating Characteristics (ROC)
      curve method. The Kappa index was used to study overall agreement with liver
      biopsy results. Interpretative algorithms were established by optimizing
      sensitivity and specificity and the percentage of correctly classified patients.
      RESULTS: One hundred and eight patients (F0-F1, n = 47; F2, n = 28; F3, n = 17;
      F4, n = 16) were considered for the evaluation of serum biomarker performance.
      The AUROCs of the Fibrotest, Hepascore, Fibrometer, and Zeng's scores ranged from
      0.74 to 0.77 for significant fibrosis (> or = F2), from 0.79 to 0.84 for advanced
      fibrosis (> or = F3) and from 0.87 to 0.92 for cirrhosis (F4). Thresholds defined
      for each stage of fibrosis were close to those previously published for the
      Fibrotest and Hepascore. Strict concordance with biopsies correctly classified
      50% of the patients. CONCLUSIONS: Fibrotest, Fibrometer, Hepascore, and Zeng's
      score were the most accurate non-invasive biochemical scores for liver fibrosis
      assessment in HIV/HBV co-infection. Global performance of biomarkers was not
      significantly improved by a decision tree combining the results of two
      biochemical scores.

PMID- 19398235
TI  - Clinical features and effect of antiviral therapy on anti-liver/kidney microsomal
      antibody type 1 positive chronic hepatitis C.
AB  - BACKGROUND/AIMS: Anti-liver/kidney microsomal antibody type 1 (anti-LKM1), a
      serological marker of type 2 autoimmune hepatitis, is also detected in a small
      proportion of patients with hepatitis C. This study aimed to evaluate clinical
      features and effect of antiviral therapy in patients with hepatitis C who are
      anti-LKM1 positive. METHODS: Sixty consecutive anti-LKM1 positive and 120 age and
      sex-matched anti-LKM1 negative chronic hepatitis C patients were assessed at
      diagnosis and during follow-up. Of these, 26 anti-LKM1 positive and 72 anti-LKM1
      negative received antiviral therapy. Anti-LKM1 was detected by indirect
      immunofluorescence and immunoblot. Number of HCV-infected hepatocytes and
      intrahepatic CD8+ lymphocytes was determined by immunohistochemistry. RESULTS: At
      diagnosis anti-LKM1 positive patients had higher IgG levels and more intrahepatic
      CD8+ lymphocytes (p 0.022 and 0.046, respectively). Viral genotypes distribution
      and response to therapy were identical. Hepatic flares during antiviral treatment
      only occurred in a minority of patients in concomitance with anti-LKM1
      positivity. CONCLUSIONS: Immune system activation is more pronounced in anti-LKM1
      positive patients with hepatitis C, possibly representing the expression of
      autoimmune mechanisms of liver damage. Antiviral treatment is as beneficial in
      these patients as in anti-LKM1 negative patients, and the rare necroinflammatory
      flares are effectively controlled by corticosteroids, allowing subsequent
      resumption of antiviral therapy.

PMID- 19398236
TI  - Signalling pathways in alcohol-induced liver inflammation.
AB  - The pathogenesis of alcoholic liver injury involves interactions of several
      intracellular signalling pathways in different cell types of the liver. Alcohol
      induced sensitization of liver macrophages to portal endotoxin/lipopolysaccharide
      (LPS) is considered a hallmark of alcoholic liver disease (ALD). Intracellular
      mechanisms associated with LPS-induced signalling play a crucial role in the
      initiation and progression of alcoholic liver injury, and are being extensively
      explored. LPS recognition by Toll-like receptor 4 (TLR4) on macrophages and other
      cell types in the liver, activation of downstream signalling pathways culminating
      in activation of transcription factors such as NFkappaB, AP-1 leads to increased
      inflammatory cytokine production in ALD. In addition, LPS-induced MAPK such as
      ERK and p38 also contribute to liver injury. The importance of alcohol-induced
      reactive oxygen species and interactions with TLR pathways in macrophages leading
      to inflammation is becoming increasingly evident. Collectively, these signalling
      pathways induce pro- and anti-inflammatory cytokines that play an important role
      in ALD. In this review we describe the key signalling intermediates leading to
      alcohol-induced inflammation in alcoholic liver disease.

PMID- 19398237
TI  - Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate
      contributes to liver fibrosis.
AB  - BACKGROUND/AIMS: Myofibroblasts play a central role in the pathogenesis of liver
      fibrosis. Myofibroblasts of bone marrow (BM) origin have recently been identified
      in fibrotic liver. However, little is known about the mechanism that controls
      their mobilization in vivo. Here we confirmed that BM mesenchymal stem cells
      (BMSCs) can migrate to the damaged liver and differentiate into myofibroblasts.
      We also investigated the mechanism underlying the homing of BMSCs after liver
      injury. METHODS: ICR mice were lethally irradiated and received BM transplants
      from enhanced green fluorescent protein transgenic mice. Carbon tetrachloride or
      bile duct ligation was used to induce liver fibrosis. The fibrotic liver tissue
      was examined by immunofluorescent staining to identify BM-derived myofibroblasts.
      RESULTS: BMSCs contributed significantly to myofibroblast population in fibrotic
      liver. Moreover, analysis in vivo and in vitro suggested that homing of BMSCs to
      the damaged liver was in response to sphingosine 1-phosphate (S1P) gradient
      between liver and BM. Furthermore, S1P receptor type 3 (S1P3) was required for
      migration of BMSCs triggered by S1P. CONCLUSIONS: S1P mediates liver fibrogenesis
      through homing of BMSCs via S1P3 receptor, which may represent a novel
      therapeutic target in liver fibrosis through inhibiting S1P formation and/or
      receptor activation.

PMID- 19398238
TI  - Iron absorption in dysmetabolic iron overload syndrome is decreased and
      correlates with increased plasma hepcidin.
AB  - BACKGROUND/AIMS: The dysmetabolic iron overload syndrome (DIOS) is a common
      disorder but its origin remains unclear. METHODS: A case-control study was
      conducted to compare intestinal absorption of iron in 16 men with DIOS (age 53 +/
      11 years, serum ferritin 750 +/- 372 microg/l, hepatic iron 78 +/- 25
      micromol/g) and in 32 age-matched controls with normal body iron stores (16
      overweight subjects and 16 lean subjects). Intestinal absorption was calculated
      as the area under the curve (AUC) of 58Fe administered orally and correlated with
      plasma hepcidin and with insulin resistance parameters including HOMA. RESULTS:
      Intestinal iron absorption was lower in DIOS (AUC = 22.4 +/- 15.9 microg/l/h)
      compared to both overweight controls (AUC = 40.5 +/- 29.4 microg/l/h, p=0.04) and
      to lean controls (AUC = 102.5 +/- 113.5 microg/l/h, p < 0.01). There was an
      inverse correlation between intestinal iron absorption and plasma hepcidin (r = 
      0.61, p < 0.001), HOMA (r = -0.35, p = 0.01) and C reactive protein (r = -0.52, p
      < 0.001). CONCLUSIONS: In overweight subjects with normal iron stores, iron
      absorption is decreased through hepcidin upregulation. In patients with DIOS,
      this decrease is more pronounced due to an additional effect of iron excess on
      circulating hepcidin levels.

PMID- 19398239
TI  - Acute hepatitis caused by a natural lipid-lowering product: when "alternative"
      medicine is no "alternative" at all.
AB  - BACKGROUND/AIMS: The general public's growing mistrust of the pharmaceutical
      industry and its perception of the lack of adverse effects of "natural" therapy
      have lead to the increasing use of "alternative drugs" for hypercholesterolemia.
      METHODS: A sixty-three year old woman presented with severe hypertransaminasemia
      that had developed progressively over a few weeks. For six months she had been
      taking Equisterol, an over-the-counter lipid-lowering product containing
      guggulsterol and red yeast rice extract. The product had been prescribed for
      hypercholesterolemia because the patient had developed hepatotoxicity while on
      lovastatin. RESULTS: Liver biopsy revealed severe lobular necroinflammatory
      changes with an eosinophilic infiltrate. The episode was regarded as an adverse
      drug reaction after exclusion of other possible causes of acute liver disease and
      the prompt normalization of liver function tests after Equisterol had been
      discontinued. Red yeast rice extract's cholesterol-lowering properties are
      largely due to fungal metabolites known as monacolins, one of which--monacolin K-
      is identical to lovastatin. CONCLUSIONS: The choice of an alternative medicine
      approach in this case subjected the patient to "re-challenge" with the official
      medicine agent that had previously caused mild hepatotoxicity. Physicians should
      keep in mind that "alternative" medicine is not always the safest alternative and
      sometimes it is not even "alternative."

PMID- 19398240
TI  - Serum vascular endothelial growth factor is related to systemic oxidative stress
      in patients with lung cancer.

PMID- 19398241
TI  - Emergency department-based HIV testing: too little, but not too late.

PMID- 19398242
TI  - National study of the emergency physician workforce, 2008.
AB  - STUDY OBJECTIVE: We describe the characteristics of the US emergency physician
      workforce. METHODS: We performed a cross-sectional analysis of the 2008 American
      Medical Association Physician Masterfile, which includes data on all physicians
      who have ever obtained a medical license in at least 1 US state. We included all
      physicians who designated emergency medicine as their primary or secondary
      specialty. RESULTS: There were 39,061 clinically active emergency physicians, of
      which 57% were emergency medicine board certified and 69% were emergency medicine
      trained or emergency medicine board certified. Family medicine (31%) and internal
      medicine (23%) were the most common backgrounds for non-emergency medicine
      trained/emergency medicine board certified emergency physicians, and most (75%)
      graduated from residency greater than or equal to 20 years ago. Nearly all (98%)
      emergency physicians who graduated within the past 5 years were emergency
      medicine trained or emergency medicine board certified. Rural emergency
      physicians were much less likely than urban emergency physicians to have
      emergency medicine training (31% versus 57%), emergency medicine board certified
      (43% versus 59%), and to have graduated in the past 5 years (8% versus 19%). The
      density of all emergency physicians per 100,000 population was highest in New
      England (16.0) and in urban areas (14.5). The lowest emergency physician
      densities were in West South Central (10.2) and rural areas (10.3). Density of
      emergency medicine-trained or emergency medicine board certified emergency
      physicians was 10.3 in urban, 5.3 in large rural, and 2.5 in small rural areas.
      CONCLUSION: Although newer emergency physicians are almost all emergency medicine
      trained or emergency medicine board certified, many non-emergency medicine
      trained/emergency medicine board certified emergency physicians still provide
      clinical coverage of EDs. Demand for all emergency physicians will likely
      continue for several decades and the shortage may even increase in rural areas.

PMID- 19398243
TI  - The association between roofing material and head injuries during the 2008
      Wenchuan earthquake in China.
AB  - STUDY OBJECTIVE: We analyze the spectrum of earthquake-related head injuries
      resulting in hospitalization and arising from the 2008 Wenchuan Earthquake in
      China. An additional objective is to assess injury patterns associated with 2
      types of roofing structures found in this region of China. METHODS: This
      descriptive study included data on trauma patients at 8 hospitals in Jiangyou for
      the 14 days immediately after the earthquake. The patients were either from
      Jiangyou County, which experienced a modified Mercalli intensity level of VIII,
      or from Beichuan County (Mercalli intensity level of X). Of the 5,775 earthquake
      related injuries, 1,484 (25.7%) involved the head and were classified into 4
      categories. Seven injury mechanisms were also analyzed to determine the
      association with the 4 types of head injuries. RESULTS: Scalp injuries (43%) were
      the most common type of head injuries, followed by facial injuries, 482 (32%),
      intracranial injuries, 218 (15%), and skull fractures, 117 (8%). Differences in
      injury type and cause were apparent, with scalp injuries being more common (49%)
      in Jiangyou than in Beichuan (30%) and falling clay tiles contributing more (40%)
      to this injury in the former city than the latter (6%). In contrast, precast
      concrete plank roofing caused 20% of scalp injuries in Beichuan compared with 3%
      in Jiangyou. CONCLUSION: Scalp injuries were the most common head injury type.
      Falling clay roofing tiles and precast concrete plank roofs are important injury
      mechanisms, and their contribution may reflect differences in building
      construction.

PMID- 19398244
TI  - E-learning may improve adherence to alcohol-based hand rubbing: a cohort study.
AB  - BACKGROUND: Since 2004, we have promoted alcohol-based hand rubbing (HR) with an
      e-learning program (ELP) among hospital staff. This study sought to determine
      whether an ELP improves adherence to correct HR. METHODS: This was a cohort study
      of staff members at Aarhus University Hospital, Skejby, Denmark who completed the
      ELP and were repeatedly observed for correct HR before and after clinical
      procedures in 2006 and/or 2007. RESULTS: Of the 496 participants, 13% completed
      the ELP in both 2006 and 2007, 29% completed the ELP only in 2006, 15% completed
      the ELP only in 2007, and 43% never completed the ELP. Compared with
      noncompleters, completers of the 2006 and 2007 ELP had a significantly higher
      adherence to correct HR both before clinical procedures (odds ratio [OR] = 1.54;
      95% confidence interval [CI] = 1.11 to 2.13) and after clinical procedures (OR =
      1.40; 95% CI = 1.03 to 1.89). Time since completing the ELP seemed to be
      inversely associated with adherence to correct HR. CONCLUSION: Completion of an
      ELP may have a positive impact on the performance of correct HR. The demands of
      lifelong education and training of hospital staff may call for the use of an ELP
      as a supplement to existing efforts aimed at improving HR to help prevent health
      care-related infections.

PMID- 19398245
TI  - Inactivation of chlorhexidine gluconate on skin by incompatible alcohol hand
      sanitizing gels.
AB  - Incompatibility of leave-on products with an antimicrobial residual can negate
      the efficacy benefits of chlorhexidine gluconate (CHG) persistence. Two marketed
      alcohol products containing Carbomer were tested using a pigskin substrate model
      against Staphylococcus aureus. The CHG residual achieved a 4.22 log(10) reduction
      (standard deviation [SD] = 0.32) in this study, which was dramatically reduced to
      a 0.54 (SD = 0.50) and 0.46 (SD = 0.56) after subsequent treatment with
      incompatible alcohol gel products. A marketed alcohol product containing a
      nonionic thickener maintained the efficacy of the CHG chemical reservoir (log(10)
      reduction = 4.26, SD = 0.00). Similar findings were demonstrated when alcohol
      solutions containing the individual thickening agents were tested as simple
      formulations. An in vivo test using human forearms and Serratia marcescens
      similarly demonstrated that the activity of a CHG reservoir (log(10) reduction =
      3.73, SD = 0.86) was not reduced by a nonionic thickened product (log(10)
      reduction = 3.98, SD = 0.72) but was significantly reduced by treatment with
      alcohol products containing anionic thickeners carbomer (log(10) reduction = 
      0.32, SD = 0.34) or acrylates/C10-30 alkyl acrylate crosspolymer (log(10)
      reduction = -0.20, SD = 0.32). The use of anionic thickeners or emulsifiers in
      leave-on products, including alcohol hand sanitizers, may inactivate the
      persistent antibacterial activity of CHG.

PMID- 19398246
TI  - Surgical site infection: incidence and impact on hospital utilization and
      treatment costs.
AB  - BACKGROUND: Surgical site infections (SSIs) are serious operative complications
      that occur in approximately 2% of surgical procedures and account for some 20% of
      health care-associated infections. METHODS: SSI was identified based on the
      presence of ICD-9-CM diagnosis code 998.59 in hospital discharge records for 7
      categories of surgical procedures: neurological; cardiovascular; colorectal;
      skin, subcutaneous tissue, and breast; gastrointestinal; orthopedic; and
      obstetric and gynecologic. Source of data was the 2005 Healthcare Cost and
      Utilization Project National Inpatient Sample (HCUP NIS). Primary study outcomes
      were rate of SSI by surgical category and impact of SSI on length of stay and
      cost. Results were projected to the national level. RESULTS: Among 723,490
      surgical hospitalizations in the sample, 6891 cases of SSI were identified (1%).
      On average, SSI extended length of stay by 9.7 days while increasing cost by
      $20,842 per admission. From the national perspective, these cases of SSI were
      associated with an additional 406,730 hospital-days and hospital costs exceeding
      $900 million. An additional 91,613 readmissions for treatment of SSI accounted
      for a further 521,933 days of care at a cost of nearly $700 million. CONCLUSION:
      SSI is associated with a significant economic burden in terms of extended length
      of stay and increased costs of treatment. Our analysis documented nearly 1
      million additional inpatient-days and $1.6 billion in excess costs.

PMID- 19398247
TI  - Impaired neurogenesis, neuronal loss, and brain functional deficits in the
      APPxPS1-Ki mouse model of Alzheimer's disease.
AB  - Amyloid-beta peptide species accumulating in the brain of patients with
      Alzheimer's disease are assumed to have a neurotoxic action and hence to be key
      actors in the physiopathology of this neurodegenerative disease. We have studied
      a new mouse mutant (APPxPS1-Ki) line developing both early-onset brain amyloid
      beta deposition and, in contrast to most of transgenic models, subsequent
      neuronal loss. In 6-month-old mice, we observed cell layer atrophies in the
      hippocampus, together with a dramatic decrease in neurogenesis and a reduced
      brain blood perfusion as measured in vivo by magnetic resonance imaging. In these
      mice, neurological impairments and spatial hippocampal dependent memory deficits
      were also substantiated and worsened with aging. We described here a phenotype of
      APPxPS1-Ki mice that summarizes several neuroanatomical alterations and
      functional deficits evocative of the human pathology. Such a transgenic model
      that displays strong face validity might be highly beneficial to future research
      on AD physiopathogeny and therapeutics.

PMID- 19398248
TI  - Attention and memory in aged rats: Impact of lifelong environmental enrichment.
AB  - Aged rodents exhibit memory and attention dysfunctions. Environmental enrichment
      (EE) attenuates memory impairments. Whether it may reduce attention deficits is
      not known. At the age of 1 month, Long-Evans female rats were placed in standard
      or EE conditions and tested after 3 (young), 12 (middle-aged) or 24 (aged) months
      of differential housing. Spatial reference memory was assessed in a water-maze
      task. Attention performance was evaluated in the five-choice serial reaction time
      (5-CSRT) task. EE improved spatial memory at all ages, but did not ameliorate 5
      CSRT performance in young and middle-aged rats; it prevented, however, the
      degradation of attention performances detected in aged rats. The number of ChAT
      (+30 to +64%)- and p75(NTR)-positive (+35 to +44%) neurons was higher in the
      basal forebrain of aged enriched vs. standard rats, suggesting their EE-mediated
      protection. The weaker deficit of attention found in aged EE rats might be linked
      to a better survival in the very long term of neurons in the basalo-cortical
      system.

PMID- 19398250
TI  - Assessement of resting energy expenditure of obese patients: comparison of
      indirect calorimetry with formulae.
AB  - BACKGROUND & AIMS: Determining the caloric expenditure of overweight (Body mass
      index - BMI from 25-29.9 kg/m(2)) or obese (BMI> or =30 kg/m(2)) patients is a
      difficult task. The importance of the measurement using indirect calorimetry (IC)
      is to avoid the administration of an inadequate caloric load, which can increase
      clinical morbidity. The aim of this study was to compare the resting energy
      expenditure (REE) obtained by IC with that estimated by the Harris-Benedict (HB)
      and the Ireton-Jones (IJ) equations and a fixed amount of 21 kcal/kg of body
      weight, using actual, average and adjusted weights. METHODS: A total of 71 IC
      measurements were prospectively performed in 44 patients using the "DELTATRAC II"
      calorimeter. In 53 of the measurements the patients were on mechanical
      ventilation and 18 were performed using the canopy, in the fasting state and 24h
      after achieving calculated caloric requirements. RESULTS: The best REE prediction
      value in the fasting state was obtained with the HB equation using the actual
      body weight (HB/ABW), 1873+/-484 kcal/day (p=0.49) when compared to the REE of
      1798+/-495 kcal/day measured by IC. After achieving caloric needs, the best REE
      prediction values were using the HB/ABW equation, 1873+/-484 kcal/day (p=0.56)
      and the IJ equation with the adjusted body weight, 2103+/-580 kcal/day (p=0.19)
      when compared to 1948+/-507 kcal/day measured by IC. Although, when the above
      results were plotted on the Bland and Altman limits of agreement test their
      average bias were low, but the ranges of their absolute values from the observed
      average agreement were large, > or =531 kcal. CONCLUSION: From these data we can
      conclude that even though the average values obtained with the equations utilized
      to predict the REE for this population, showed good correlation with those by IC,
      as they had the best comparative absolute results, however they demonstrated an
      unacceptable variability when matched to the measured REE values.

PMID- 19398249
TI  - Neurotrophic signaling molecules associated with cholinergic damage in young and
      aged rats: environmental enrichment as potential therapeutic agent.
AB  - The aim of this study was to determine the neurobiological bases of behavioral
      deficits associated with cholinergic damage and the potential of long-term
      environmental enrichment as a therapeutic agent. Rats were submitted to intra
      structures injection of 192 IgG-saporin and then behaviorally tested 1 month and
      1 year post-lesion in a nonmatching-to-position task. The gene expression changes
      were assessed by cDNA macroarray technology using the GE array Q series designed
      to profile the expression of neurotrophic signaling molecules. Results showed
      that (1) cholinergic injury modulated the expression of genes such as brain
      derived neurotrophin factor but also genes associated with inflammatory response,
      neuron apoptosis, regulation of angiogenesis, and synaptic plasticity, (2) aging
      is associated with regulation of glial proliferation and apoptosis, and (3) long
      term enriched environment housing enhanced behavioral performance in lesioned and
      non-lesioned rats and upregulated gene expression. This therapeutic role of the
      enriched environment seemed to be associated with a suppression of expression of
      genes involved in apoptosis, glial cell differentiation, and cell cycle, but also
      with an enhanced expression of a subset of genes involved in signal transduction.

PMID- 19398251
TI  - Natural radioactivity in refractory manufacturing plants and exposure of workers
      to ionising radiation.
AB  - This paper shows the results of a survey carried out at some refractory
      manufacturing plants. During the first part of the survey, the concentration of
      natural radioactivity in raw materials and end-products, coming from four plants,
      was assessed. Several raw materials and, as a consequence, some end-products as
      well have shown activity concentrations exceeding a few hundreds of Bq kg(-1) of
      (238)U and (232)Th. In some important raw materials, such as bauxite and
      corundums, a remarkable radioactive disequilibrium was observed; this is probably
      due to the high temperature processes undergone by these materials. The second
      part of the survey focussed on the measurements of ambient equivalent dose rates,
      airborne dust concentrations and radon indoor. On the basis of results obtained,
      the effective dose for the standard worker was estimated. Two different types of
      refractory plants were investigated. Effective doses for both plants were lower
      than 1 mSv y(-1).

PMID- 19398252
TI  - Downregulation of Notch1 and its potential correlation with epidermal growth
      factor receptor signalling in tongue squamous cell carcinoma.
AB  - We investigated the expression of Notch1 in human oral squamous cell carcinoma
      (SCC) and explored its potential correlation with epidermal growth factor
      receptor (EGFR) signalling in oral SCC. Paraffin sections of primary SCC of the
      tongue and normal mucosa were screened immunohistochemically for Notch1 and EGFR
      proteins. Human SCC of the tongue Tca8113 cells were treated with AG1478 to block
      EGFR signalling, and were transfected with the vector that encodes the specific
      short hairpin RNA (shRNA) that targets EGFR. In SCC of the tongue expression of
      Notch1 was cancelled except in sites of squamous metaplasia where it was raised,
      while expression of EGFR was found in the peripheral cells of carcinomas, but not
      in sites of squamous metaplasia. In normal tongue mucosa, Notch1 was expressed
      mainly in the stratum corneum, but not in the stratum basale, while EGFR was
      expressed mainly in the stratum basale, but not in the stratum granulosum or
      stratum corneum. The blocking of EGFR signalling or the silencing of the EGFR
      gene resulted in upregulation of Notch1 at mRNA and protein levels in Tca8113
      cells. These observations suggest that downregulation of Notch1 in oral SCC may
      be associated with upregulation of EGFR signalling.

PMID- 19398253
TI  - Evaluation of oral vascular anomalies using optical coherence tomography.
AB  - Optical coherence tomography (OCT) is a new method of biomedical imaging that can
      generate high-resolution, cross-sectional images of microstructures. The purpose
      of this study was to present the first OCT images of oral vascular anomalies
      using a new advanced OCT scanner that we have developed, and to discuss the
      application of our system for oral soft tissues. Knowledge of the size and area
      of the vascular structures can be useful for the diagnosis and choice of the best
      treatment. Before excision, oral vascular malformations were assessed by OCT in
      vivo. Histopathological sections were taken and compared with the OCT images to
      make clinicopathological correlations. OCT provided clear images of all the
      vascular lesions examined. Oval to roundish, signal-poor areas sharply demarcated
      by a surrounding signal-rich layer correlated well with the histopathological
      diagnosis. OCT images provide information about subsurface structure non
      invasively that is otherwise obtainable only by examination of a biopsy specimen.
      The analysis of oral vascular lesions by OCT provides new insights into non
      invasive diagnosis and can be helpful in the selection of the most appropriate
      treatment.

PMID- 19398254
TI  - Menstrual cycle variations in oestradiol and progesterone have no impact on in
      vivo medial gastrocnemius tendon mechanical properties.
AB  - BACKGROUND: Tendon tissue contains oestrogen receptors and is therefore likely to
      be responsive to female sex hormones. Here we examine any effect of levels of
      female sex hormones associated with the menstrual cycle phase on corresponding
      tendon mechanical properties. METHODS: Fifteen healthy females aged 23 (SEM 1.0
      years) underwent three assessments of medial gastrocnemius tendon mechanical
      properties. Assessments were carried out once during days 1-4, 12-14 and 20-23
      (with day 1 being the first day of menstruation). Venous blood samples were taken
      on the same days as tendon properties assessments to quantify serum levels of
      oestradiol and progesterone. FINDINGS: There was no significant difference in the
      stiffness of the medial gastrocnemius tendon over the course of the menstrual
      cycle (days 1-4, 65.08 (SEM 5.16 Nm m(-1)), days 12-14, 62.73 (SEM 5.82 Nm m(
      1)), days 20-23, 66.74 (SEM 7.14 Nm m(-1))). There were also no significant
      differences in tendon length and cross-sectional area which led to no significant
      differences in Young's modulus values. No correlations were found between serum
      levels of oestradiol and/or progesterone and tendon stiffness and/or Young's
      modulus. INTERPRETATION: Acute fluctuations in female sex hormones have no
      significant effect on medial gastrocnemius tendon mechanical properties. In a
      context where studies are often limited to selecting only oral contraceptive
      users as participants in order to minimise potential noise related to the
      anticipated effects of menstrual cycle hormones on physical performance, our
      findings provide the basis for enabling the pooling of female tendon data,
      regardless of the phase of the menstrual cycle of individual participant.

PMID- 19398255
TI  - Mercury bioaccumulation and risk to three waterbird foraging guilds is influenced
      by foraging ecology and breeding stage.
AB  - We evaluated mercury (Hg) in five waterbird species representing three foraging
      guilds in San Francisco Bay, CA. Fish-eating birds (Forster's and Caspian terns)
      had the highest Hg concentrations in their tissues, but concentrations in an
      invertebrate-foraging shorebird (black-necked stilt) were also elevated. Foraging
      habitat was important for Hg exposure as illustrated by within-guild differences,
      where species more associated with marshes and salt ponds had higher
      concentrations than those more associated with open-bay and tidal mudflats.
      Importantly, Hg concentrations increased with time spent in the estuary. Surf
      scoter concentrations tripled over six months, whereas Forster's terns showed an
      up to 5-fold increase between estuary arrival and breeding. Breeding waterbirds
      were at elevated risk of Hg-induced reproductive impairment, particularly
      Forster's terns, in which 48% of breeding birds were at high risk due to their Hg
      levels. Our results highlight the importance of habitat and exposure timing, in
      addition to trophic position, on waterbird Hg bioaccumulation and risk.

PMID- 19398256
TI  - [Lung disease secondary to morphea en coup de sabre, a form of localized
      scleroderma].

PMID- 19398257
TI  - The effect of thermal cycling on metal-ceramic bond strength.
AB  - OBJECTIVES: The aim was to evaluate the effect of thermal cycling on the metal
      ceramic bond strength. METHODS: Four different noble metal alloys were used.
      Specimens for the crack initiation test according to ISO 9693 were prepared to
      assess metal-ceramic bond strength (n=10). The metal substrates were either air
      borne particle abraded or polished prior to veneering. Bond strength was measured
      after veneering or after 6000 thermal cycles. With one alloy in addition long
      term thermal cycling with 15,000 and 50,000 cycles was carried out. Statistical
      analysis was performed with one-way ANOVA followed by a post hoc Bonferroni test.
      RESULTS: Polished metal substrates showed a significantly lower bond strength
      compared to the air-borne particle abraded substrates. Treatment with 6000
      thermal cycles did not significantly reduce the bond strength. Long-term thermal
      cycling resulted in an exponential decrease of bond strength for both polished
      and air-borne particle abraded specimens. CONCLUSIONS: Air-borne particle
      abrasion significantly increases metal-ceramic bond strength. Thermal cycling of
      metal-ceramic composites results in an exponential decrease of bond strength. The
      crack initiation test is a sensitive method for assessing the metal-ceramic bond
      strength.

PMID- 19398258
TI  - Influence of power density on the setting behaviour of light-cured glass-ionomer
      cements monitored by ultrasound measurements.
AB  - OBJECTIVES: To monitor the influence of the power density of the curing unit on
      the setting behaviour of light-cured glass-ionomer cements (LCGICs) using
      ultrasound measurements. METHODS: The ultrasound equipment comprised a pulser
      receiver, transducers and an oscilloscope. The LCGICs used were Fuji II LC, Fuji
      II LC EM and Fuji Filling LC. The cements were mixed according to the
      manufacturer's instructions and then inserted into a transparent mould. The
      specimens were placed on the sample stage and cured with power densities of 0 (no
      irradiation), 200 or 600 mW/cm(2). The transit time through the cement disk was
      divided by the specimen thickness and then the longitudinal ultrasound velocity
      (V) within the material was obtained. Analysis of variance and Tukey's Honestly
      Significantly Different test were used to compare the V values between the set
      cements. RESULTS: When the LCGICs were light-irradiated, each curve displayed an
      initial plateau at approximately 1500 m/s and then rapidly increased to a second
      plateau at approximately 2600 m/s. The rate of increase of V was retarded when
      the cements were light-irradiated with a power density of 200 mW/cm(2) than with
      a power density of 600 mW/cm(2). Although sonic echoes were detected from the
      beginning of the measurements, the rates of increase of the sonic velocity were
      relatively slow when the cement was not light-irradiated. CONCLUSIONS: The
      ultrasound device monitored the setting processes of LCGICs accurately based on
      the longitudinal V. The polymerization behaviour of LCGICs was shown to be
      affected by the power density of the curing unit.

PMID- 19398259
TI  - Obstetrical prognosis and pregnancy outcome following pelvic arterial
      embolisation for post-partum hemorrhage.
AB  - Post-partum hemorrhage is an obstetrical emergency. Pelvic artery embolisation
      offers an alternative to surgical intervention and increases the rate of
      conservative treatment. The objective of this review was to study the scientific
      literature on obstetrical outcomes following uterine-sparing arterial
      embolisation performed for post-partum hemorrhage in a prior pregnancy. A Medline
      and Sciencedirect search were performed in order to review all the French and
      English reports about pregnancy following pelvic arteries embolisation for post
      partum hemorrhage. Nineteen articles were identified and 13 were selected for
      inclusion. We have included the fertility follow-up of a total of 168 women who
      underwent pelvic arteries embolisation for post-partum hemorrhage. We highlight
      the clinical success of embolisation in 154 of the 168 patients (92%). Following
      the embolisation procedures, 7 hysterectomies were required and 4 patients died.
      Two of the 4 deaths occurred in women who were transferred from an outlying
      institution to a tertiary referral center. In this population, 45 pregnancies
      were described. Among these pregnancies, 32 resulted in live births (71%), 8 were
      miscarriages (18%) and 5 patients carried out voluntary termination of pregnancy
      (11%). The cesarean section rate was 62%. Post-partum hemorrhage occurred in 6
      cases leading to 2 hysterectomies. In conclusion, pelvic arterial embolisation
      offers a safe and conservative alternative to surgical interventions for post
      partum hemorrhage in well-selected patients desiring to preserve future
      fertility.

PMID- 19398260
TI  - Laparoscopic versus open myomectomy--a meta-analysis of randomized controlled
      trials.
AB  - The objective of this study was to determine the better method of myomectomy by
      comparing laparoscopic and open myomectomy for patients with fibroids with regard
      to operative parameters and outcomes. A systematic review was performed on
      published studies identified by the databases PubMed, EMBASE, the China
      Biological Medicine Datadase (CBMdisc), Ovid and the Cochrane Library, as well as
      cross-references. Randomized controlled trials on laparoscopic versus open
      myomectomy were assessed on operative parameters and outcomes. Six studies and
      576 patients were studied. Analysis was performed using the statistical software
      Review Manager Version 4.2. The data available show that laparoscopic myomectomy
      was associated with less hemoglobin drop, reduced operative blood loss, more
      patients fully recuperated at day 15, diminished postoperative pain, and fewer
      overall complications but longer operation time. However, major complications,
      pregnancy and recurrence were comparable in the two groups. The data show that if
      performed by suitably specialized surgeons in selected patients, laparoscopic
      myomectomy is a better choice than open surgery.

PMID- 19398261
TI  - Molecular dynamics simulation study of valyl-tRNA synthetase with its pre- and
      post-transfer editing substrates.
AB  - The main role of aminoacyl-tRNA synthetases (aaRSs) is to transfer the cognate
      amino acids to the 3'-end of their tRNA by strictly discriminating from non
      cognate amino acids. Some aaRSs accomplish this via proofreading and editing
      mechanisms, among which valyl-tRNA synthetase (ValRS) hydrolyses the non-cognate
      amino acid, threonine. In ValRS, existence of pre-transfer editing process is
      still unclear, although crystal structure of editing site with pre-transfer
      substrate analog (Thr-AMS) was released. In the case of isoleucyl-tRNA synthetase
      (IleRS), editing mechanism is well studied and mutational analyses revealed the
      existence of post- and pre-transfer editing mechanisms. Our aim is to investigate
      the possibility of pre-transfer editing process by performing molecular dynamics
      (MD) simulation studies. Simulations were carried out for ValRS with pre-transfer
      substrates (Thr-AMP/Val-AMP) and post-transfer substrates (Thr-A76/Val-A76) to
      understand their binding pattern. Two important point mutation studies were
      performed to observe their effect on editing process. This study also intends to
      compare and contrast the pre-transfer editing with post-transfer editing of
      ValRS. Interestingly, the MD simulation results revealed that non-cognate
      substrates (Thr-AMP/Thr-A76) bind more strongly than the cognate substrates (Val
      AMP/Val-A76) in both pre- and post-transfer editing respectively. The editing
      site mutations (Lys270Ala and Asp279Ala) severely affected the binding ability of
      pre-transfer substrate (Thr-AMP) by different ways. Even though pre- and post
      transfer substrates bind to the same site, specific differences were observed
      which has led us to believe the existence of the pre-transfer editing process in
      ValRS.

PMID- 19398262
TI  - Gene expression profiles of human inner cell mass cells and embryonic stem cells.
AB  - Human embryonic stem cell (hESC) lines are derived from the inner cell mass (ICM)
      of preimplantation human blastocysts obtained on days 5-6 following
      fertilization. Based on their derivation, they were once thought to be the
      equivalent of the ICM. Recently, however, studies in mice reported the derivation
      of mouse embryonic stem cell lines from the epiblast; these epiblast lines bear
      significant resemblance to human embryonic stem cell lines in terms of culture,
      differentiation potential and gene expression. In this study, we compared gene
      expression in human ICM cells isolated from the blastocyst and embryonic stem
      cells. We demonstrate that expression profiles of ICM clusters from single
      embryos and hESC populations were highly reproducible. Moreover, comparison of
      global gene expression between individual ICM clusters and human embryonic stem
      cells indicated that these two cell types are significantly different in regards
      to gene expression, with fewer than one half of all genes expressed in both cell
      types. Genes of the isolated human inner cell mass that are upregulated and
      downregulated are involved in numerous cellular pathways and processes; a subset
      of these genes may impart unique characteristics to hESCs such as proliferative
      and self-renewal properties.

PMID- 19398263
TI  - TWEAK promotes ovarian cancer cell metastasis via NF-kappaB pathway activation
      and VEGF expression.
AB  - The poor prognosis of human ovarian cancer is partly due to its metastasis and
      recurrence. It has been demonstrated that tumor necrosis factor (TNF)-like weak
      inducer of apoptosis (TWEAK)-fibroblast growth factor inducible-14 (Fn14)
      signaling system may be a potential regulator of human tumorigenesis. The
      objective of this study was to understand the effect of TWEAK on ovarian cancer
      metastasis. We recently showed that activation of Fn14 signaling by TWEAK
      promoted cell migration and invasion in human HO-8910PM cells. Treating HO-8910PM
      cells with TWEAK resulted in the activation of nuclear factor-kappa B (NF-kappaB)
      and subsequently the translocation of NF-kappaB from cytoplasm to nucleus. In
      addition, TWEAK promoted vascular endothelial growth factor (VEGF) protein
      expression, and this effect was dependent upon NF-kappaB transcriptional
      activity. Blocking the NF-kappaB pathway with PDTC suppressed TWEAK-induced up
      regulation of VEGF protein expression and cell metastasis. Our results suggest
      that TWEAK-Fn14 functions, in part, through the NF-kappaB signaling pathway to up
      regulate VEGF expression to foster ovarian cancer cell metastasis. Targeted
      therapy against TWEAK-Fn14 signaling system as an adjuvant to surgery may improve
      clinical management of invasive ovarian cancer cells and advance the outcome of
      this devastating cancer.

PMID- 19398264
TI  - Effect of particle size on thermal decomposition of nitrocellulose.
AB  - Data on the thermal stability of energetic materials such as nitrocellulose were
      required in order to obtain safety information for handling, storage and usage.
      In present study, the thermal stability of micron and nano-sized nitrocellulose
      samples was determined by differential scanning calorimetry (DSC) and
      simultaneous thermogravimetry-differential thermal analysis (TG/DTA) techniques.
      The results of TG analysis revealed that the main thermal degradation of
      nitrocellulose occurs in the temperature range of 190-210 degrees C. On the other
      hand, the TG-DTA analysis of samples indicated that particle size of
      nitrocellulose could affect on its thermal stability and its decomposition
      temperature decreases by decreasing its particle size. The influence of the
      heating rate (5, 10, 15 and 20 degrees C/min) on the DSC behaviour of the
      nitrocellulose with two particle sizes was verified. The results showed that, as
      the heating rate was increased, decomposition temperature of the micron and nano
      sized compound was increased. Also, the kinetic parameters such as activation
      energy and frequency factor for the micron and nano-sized nitrocellulose were
      obtained from the DSC data by non-isothermal methods proposed by ASTM E696 and
      Ozawa.

PMID- 19398265
TI  - Biomolecule-controlled hydrothermal synthesis of C-N-S-tridoped TiO2
      nanocrystalline photocatalysts for NO removal under simulated solar light
      irradiation.
AB  - In this study, C-N-S-tridoped titanium dioxide (TiO(2)) nanocrystals were
      synthesized by using a facile hydrothermal method in the presence of a
      biomolecule l-cysteine. This biomolecule could not only serve as the common
      source for the carbon, sulfur and nitrogen tridoping, but also could control the
      final crystal phases and morphology. The resulting materials were characterized
      by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), nitrogen
      adsorption and UV-vis diffuse reflectance spectroscopy. XPS analysis revealed
      that S was incorporated into the lattice of TiO(2) through substituting oxygen
      atoms, N might coexist in the forms of N-Ti-O and Ti-O-N in tridoped TiO(2) and
      most C could form a mixed layer of carbonate species deposited on the surface of
      TiO(2) nanoparticles. The photocatalytic activities of the samples were tested on
      the removal of NO at typical indoor air level in a flow system under simulated
      solar light irradiation. The tridoped TiO(2) samples showed much higher removal
      efficiency than commercial P25 and the undoped counterpart photocatalyst. The
      enhanced visible light photocatalytic activity of C-N-S-tridoped TiO(2)
      nanocrystals was explained on the basis of characterizations. The possible
      formation process of the monodispersed C-N-S-tridoped anatase TiO(2) nanocrystals
      was also proposed. This study provides a new method to prepare visible light
      active TiO(2) photocatalyst.

PMID- 19398266
TI  - Interior microelectrolysis oxidation of polyester wastewater and its treatment
      technology.
AB  - This paper has investigated the effects of interior microelectrolysis
      pretreatment on polyester wastewater treatment and analyzed its mechanism on COD
      and surfactant removal. The efficiency of interior microelectrolysis is mainly
      influenced by solution pH, aeration and reaction time. Contaminants can be
      removed not only by redox reaction and flocculation in the result of ferrous and
      ferric hydroxides but also by electrophoresis under electric fields created by
      electron flow. pH confirms the chemical states of surfactants, Fe(II)/Fe(III)
      ratio and the redox potential, and thus influences the effects of
      electrophoresis, flocculation and redox action on contaminant removal. Anaerobic
      and aerobic batch tests were performed to study the degradation of polyester
      wastewater. The results imply that interior microelectrolysis and anaerobic
      pretreatment are lacking of effectiveness if applied individually in treating
      polyester wastewater in spite of their individual advantages. The interior
      microelectrolysis-anaerobic-aerobic process was investigated to treat polyester
      wastewater with comparison with interior microelectrolysis-aerobic process and
      anaerobic-aerobic process. High COD removal efficiencies have been gotten by the
      combination of interior microelectrolysis with anaerobic technology and aerobic
      technology. The results also imply that only biological treatment was less
      effective in polyester wastewater treatment.

PMID- 19398267
TI  - Preconcentration of some trace elements via using multiwalled carbon nanotubes as
      solid phase extraction adsorbent.
AB  - In present study preconcentration followed by solid phase extraction of heavy
      metal ions, Cu(II), Co(II), Ni(II) and Pb(II) using a multiwalled carbon
      nanotubes (MWNTs) and complexing reagent o-cresolphthalein complexone were
      investigated. The effects of parameters, including pH of the solutions, amounts
      of complexing reagent, eluent type, sample volume, flow rates of solution, and
      matrix ions, were examined for the optimum recoveries of the analyte ions. The
      preconcentration factor was 40. Detection limit (3s) obtained for the
      investigated metals in the optimal conditions were observed in the range of 1.64
      5.68 microg l(-1). The validation of the presented method was obtained by the
      analysis of certified reference material HR 1 (Humber river sediment), the
      obtained results were agreed with certified values. The optimum experimental
      conditions that ensure the efficiency of the procedure have been investigated and
      have been successfully applied to the determination of trace elements in
      environmental samples with satisfactory results.

PMID- 19398268
TI  - Simultaneous determination of zinc, cadmium and lead in environmental water
      samples by potentiometric stripping analysis (PSA) using multiwalled carbon
      nanotube electrode.
AB  - The present paper has focused on the potential application of multiwalled carbon
      nanotube for the development of a new, simple and highly selective
      electrochemical method for simultaneous Zn (II), Cd (II) and Pb (II) monitoring
      in water samples (lake and effluent waters), by using potentiometric stripping
      analysis (PSA). The electrochemical method is based on simultaneous
      preconcentration/reduction of metal ions onto a multiwall carbon nanotube
      electrode at -1.3V (versus Ag/AgCl(sat)) in 0.3 mol L(-1) acetate solution
      containing 15 mg L(-1) Hg (II) ions during 180s, followed by subsequent chemical
      stripping. The analytical curve for all analytes covered the linear range varying
      from 58.4 up to 646.2 microg L(-1) with correlation coefficients higher than
      0.981. The limits of detection for Zn (II), Cd (II) and Pb (II) were found to be
      28.0, 8.4 and 6.6 microg L(-1), while the relative standard deviation (RSD) at
      352 microg L(-1) was 5.6, 7.1 and 5.6% (n=5), respectively. The behavior of the
      simultaneous determination in the presence of following ions Co (II), Cr (III)
      and Cu (II) was affected by using the analyte:interferent ratio 1:10. Therefore,
      by using standard addition method, Zn (II), Cd (II) and Pb (II) ions in lake and
      effluent water samples were determined after the spiking procedure and the
      results were successfully compared with those obtained by atomic absorption
      spectrometry (AAS). The obtained results suggest that the proposed method can be
      applied as a simple and efficient alternative for the simultaneous monitoring of
      heavy metals in water samples, according to those established requirements from
      environmental organizations. In addition, this method demonstrates the powerful
      application of carbon nanotubes in the field of potentiometric stripping
      analysis.

PMID- 19398269
TI  - Preparation of p-tert[(dimethylamino)methyl]-calix[4]arene functionalized
      aminopropylpolysiloxane resin for selective solid-phase extraction and
      preconcentration of metal ions.
AB  - A new p-tert-[(dimethylamino)methyl]-1,3-bisglyciyl-calix[4]arene functionalized
      aminopropylpolysiloxane resin (APPS-CA) has been prepared and investigated for
      selective solid-phase extraction (SPE) of trace Cr (III), Cu (II), Ni (II), Co
      (II) and Zn (II) prior to their determination by inductively coupled plasma
      optical emission spectrometry (ICP-OES). The characterization of the surface
      modification was performed on the basis of FT-IR spectroscopy, elemental analysis
      and thermal gravimetric analysis. The separation/preconcentration conditions of
      analytes were investigated, including effect of pH, the shaking time, the sample
      flow rate and volume, the elution condition, the interfering ions and stability
      test. At pH 4.0, the maximum adsorption capacity of Cr (III), Cu (II), Ni (II),
      Co (II) and Zn (II) were 47.2, 34.3, 52.8, 29.8 and 36.4 mg g(-1), respectively.
      The adsorbed metal ions were quantitatively eluted by 2.0 mL of 0.5 mol L(-1)
      HCl. Common coexisting ions did not interfere with the separation. According to
      the definition of International Union of Pure and Applied Chemistry, the
      detection limits (3 sigma) of this method were found to be 0.58, 0.33, 0.47, 0.61
      and 0.14 ng mL(-1) for Cr (III), Cu (II), Ni (II), Co (II) and Zn (II),
      respectively. The relative standard deviation under optimum conditions is less
      than 4.0%. The application of this new adsorbent to preconcentration trace Cr
      (III), Cu (II), Ni (II), Co (II) and Zn (II) of two water samples gave high
      accurate and precise results.

PMID- 19398270
TI  - Start-up of simultaneous removal of ammonium and sulfate from an anaerobic
      ammonium oxidation (anammox) process in an anaerobic up-flow bioreactor.
AB  - A laboratory testing of simultaneous removal of ammonium and sulfate (SRAS) was
      studied from an anammox process in an anaerobic bioreactor filled with granular
      activated carbon. Two different phases of experiment were investigated to start
      up the SRAS process, and final batch tests were performed to analyze the SRAS
      process. The experiment included an anammox process and an SRAS process. During
      the anammox process, the highest removal efficiency of ammonium and nitrite was
      up to 97 and 98%, respectively. After 160 days in the stationary phase of anammox
      process, the ratio of ammonium to nitrite consumption was approximately 1:1.15,
      which is much higher than 1:1.32 in the traditional anammox process. The extra
      electron acceptor, such as sulfate, was thought to react with ammonium by
      bacteria. Synthetic wastewater containing ammonium chlorine and sodium sulfate
      was used as the feed for the bioreactor in the second phase of experiment. During
      the SRAS process, the influent concentrations of ammonium and sulfate were
      controlled to be 50-60 and 210-240 mg L(-1) respectively. After start-up and
      acclimatization of this process for 60 days, the average effluent concentrations
      of ammonium and sulfate were 30 and 160 mg L(-1), respectively. The simultaneous
      ammonium and sulfate removal was detected in the reactor. In order to further
      validate the biochemical interaction between ammonium and sulfate, batch tests
      was carried out. Abiotic tests were carried out to demonstrate that the pure
      chemical action between ammonium and sulfate without microorganism was not
      possible. Biotic assays with different ammonium and sulfate concentrations were
      further investigated that high concentrations of ammonium and sulfate could
      promote simultaneous removal of ammonium and sulfate. And elemental sulfur and
      nitrogen gas as the products measured in the SRAS process helped to demonstrate
      the occurrence of new interaction between nitrogen and sulfur. The new process of
      SRAS in the inorganic condition, including simultaneous removal of ammonium and
      sulfate, and the appearance of elemental sulfur and nitrogen gas as the terminal
      products, widened the cycle approach between nitrogen and sulfur.

PMID- 19398271
TI  - Activation of Firmiana Simplex leaf and the enhanced Pb(II) adsorption
      performance: equilibrium and kinetic studies.
AB  - Although various biosorbents have been reported effective to purify wastewaters
      containing heavy metals, the high tendency to decomposition in the environment
      makes them unsuitable for long-term persistent utilization. In this paper, a
      simple and new activation method was proposed to mineralize the Firmiana Simplex
      leaf (FSL) into an enhanced adsorbent for Pb(II) removal from aqueous solution.
      The leaves activated at various temperatures were characterized with BET N(2)
      adsorption test, FT-IR test and XRD test. After activation, the mass percent of
      inorganic components (including whewellite, quartz, phosphate and calcite)
      increased and the specific surface area increased from 0.08283 to 9.32 m(2)g(-1)
      with the increasing activation temperature (AT) from 100 to 400 degrees C. Proper
      activation temperature (200 degrees C) helps to preserve the beneficial groups
      (amine and carboxyl). The affinities of the adsorbents towards Pb(II) were
      increased with increasing AT from 300, 100, 200 to 400 degrees C according to the
      adsorption isotherms. The adsorbent activated at 200 degrees C (AL2) was found
      most suitable for Pb(II) adsorption regarding the high yield efficiency (36.52%),
      high Pb(II) adsorption capacity (136.7 mg g(-1) by Langmuir model), high
      adsorption affinity (H type isotherm) and rapid adsorption rate (within 20 min by
      kinetic study). The Pb(II) removal efficiency of AL2 was obviously affected by
      the solution pH rather than by the adsorbent dosage. The adsorption was viewed as
      a chemical process based on IR spectra along with a physical process based on the
      correlation between the average pore size of the adsorbent and the adsorption
      capacity. The activation method proposed in this paper was proved effective and
      potentially applicable in the treatment of Pb(II) polluted wastewaters.

PMID- 19398272
TI  - Exploring relationships for visceral and somatic pain with autonomic control and
      personality.
AB  - The autonomic nervous system (ANS) integrates afferent and motor activity for
      homeostatic processes including pain. The aim of the study was to compare
      hitherto poorly characterised relations between brainstem autonomic control and
      personality in response to visceral and somatic pain. Eighteen healthy subjects
      (16 females, mean age 34) had recordings during rest and pain of heart rate (HR),
      cardiac vagal tone (CVT), cardiac sensitivity to baroreflex (CSB), skin
      conductance level (SC), cardiac sympathetic index (CSI) and mean blood pressure
      (MBP). Visceral pain was induced by balloon distension in proximal (PB) and
      distal (DB) oesophagus and somatic pain by nail-bed pressure (NBP). Eight painful
      stimuli were delivered at each site and unpleasantness and intensity measured.
      Personality was profiled with the Big Five inventory. (1) Oesophageal intubation
      evoked "fight-flight" responses: HR and sympathetic (CSI, SC, MBP) elevation with
      parasympathetic (CVT) withdrawal (p<0.05). (2) Pain at all sites evoked novel
      parasympathetic/sympathetic co-activation with elevated HR but vasodepression
      (all p<0.05). (3) Personality traits correlated with slope of distal oesophageal
      pain-related CVT changes wherein more neurotic-introvert subjects had greater
      positive pain-related CVT slope change (neuroticism r 0.8, p<0.05; extroversion r
      -0.5, p<0.05). Pain-evoked heart rate increases were mediated by parasympathetic
      and sympathetic co-activation - a novel finding in humans but recently described
      in mammals too. Visceral pain-related parasympathetic change correlated with
      personality. ANS defence responses are nuanced and may relate to personality type
      for visceral pain. Clinical relevance of these findings warrants further
      exploration.

PMID- 19398273
TI  - Effect of SP-C on surface potential distribution in pulmonary surfactant: Atomic
      force microscopy and Kelvin probe force microscopy study.
AB  - The air-lung interface is covered by a molecular film of pulmonary surfactant
      (PS). The major function of the film is to reduce the surface tension of the
      lung's air-liquid interface, providing stability to the alveolar structure and
      reducing the work of breathing. Earlier we have shown that function of bovine
      lipid extract surfactant (BLES) is related to the specific molecular architecture
      of surfactant films. Defined molecular arrangement of the lipids and proteins of
      the surfactant film also give rise to a local highly variable electrical surface
      potential of the interface. In this work we investigated a simple model of
      artificial lung surfactant consisting of DPPC, eggPG, and surfactant protein C
      (SP-C). Effects of surface compression and the presence of SP-C on the monolayer
      structure and surface potential distribution were investigated using atomic force
      microscopy (AFM) and Kelvin probe force microscopy (KPFM). We show that
      topography and locally variable surface potential of DPPC-eggPG lipid mixture are
      similar to those of pulmonary surfactant BLES in the presence of SP-C and differ
      in surface potential when SP-C is absent.

PMID- 19398274
TI  - Spin-charge separation and electron pairing instabilities in Hubbard
      nanoclusters.
AB  - Electron charge and spin pairing instabilities in various cluster geometries for
      attractive and repulsive electrons are studied exactly under variation of
      interaction strength, electron doping and temperature. The exact diagonalization,
      level crossing degeneracies, spin-charge separation and separate condensation of
      paired electron charge and opposite spins yield intriguing insights into the
      origin of magnetism, ferroelectricity and superconductivity seen in inhomogeneous
      bulk nanomaterials and various phenomena in cold fermionic atoms in optical
      lattices. Phase diagrams resemble a number of inhomogeneous, coherent and
      incoherent nanoscale phases found recently in high-T(c) cuprates, manganites and
      multiferroic nanomaterials probed by scanning tunneling microscopy. Separate
      condensation of electron charge and spin degrees at various crossover
      temperatures offers a new route for superconductivity, different from the BCS
      scenario. The calculated phase diagrams resemble a number of inhomogeneous paired
      phases, superconductivity, ferromagnetism and ferroelectricity found in Nb and Co
      nanoparticles. The phase separation and electron pairing, monitored by electron
      doping and magnetic field surprisingly resemble incoherent electron pairing in
      the family of doped high-T(c) cuprates, ruthenocuprates, iron pnictides and
      spontaneous ferroelectricity in multiferroic materials.

PMID- 19398275
TI  - Zoonotic parasites in fecal samples and fur from dogs and cats in The
      Netherlands.
AB  - Pets may carry zoonotic pathogens for which owners are at risk. The aim of the
      study is to investigate whether healthy pets harbour zoonotic parasitic
      infections and to make an inventory of the interactions between pet-owners and
      their companion animals in The Netherlands. Fecal and hair samples were collected
      from healthy household dogs and cats in Dutch veterinary practices. Owners were
      interviewed about interaction with their pets. The samples were investigated by
      microscopy, ELISA, and PCR. From 159 households, 152 dogs (D) and 60 cats (C),
      information and samples were collected and examination for several zoonotic
      parasites was performed. Toxocara eggs were found in 4.4% (D) and 4.6% (C) of the
      fecal samples and in 12.2% (D) and 3.4% (C) of the fur samples. The median epg in
      the fur was 17 (D) and 28 (C) and none of these eggs were viable. From 15.2% of
      the dog and 13.6% of the cat feces Giardia was isolated. One canine and one
      feline Giardia isolate was a zoonotic assemblage A (12%). Cryptosporidium sp.
      were present in 8.7% (D) and 4.6% (C) of the feces. Fifty percent of the owners
      allow the pet to lick their faces. Sixty percent of the pets visit the bedroom;
      45-60% (D-C) are allowed on the bed, and 18-30% (D-C) sleep with the owner in
      bed. Six percent of the pets always sleep in the bedroom. Of the cats, 45% are
      allowed to jump onto the kitchen sink. Nearly 39% of the dog owners never clean
      up the feces of their dog. Fifteen percent of the dog owners and 8% of the cat
      owners always wash their hands after contact with the animals. Close physical
      contact between owners and their pets is common and poses an increased risk of
      transmission of zoonotic pathogens. Education of owners by the vet, specifically
      about hygiene and potential risks, is required.

PMID- 19398276
TI  - Pathophysiology in Teladorsagia (Ostertagia) circumcincta-infected sheep selected
      for high fleece weight.
AB  - Resilience to parasitism is considered to be the maintenance of growth and
      production during infection, probably associated with an immune response with
      lesser detrimental effects on the host relative to adverse effects on the
      parasite. Resilience to infection with Teladorsagia circumcincta was investigated
      in lambs from a flock selected for forty generations for high fleece weight
      (HFW), but with higher FEC and worm burdens than their unselected control (C)
      flock run in parallel. After recovery from surgery to implant abomasal cannulae,
      four parasite-naive lambs from each flock were infected intraruminally at 6.5
      months-of-age with 50,000 T. circumcincta L3, then from Day 35 to 70 post
      infection with 10,000 larvae at weekly intervals. Blood, abomasal fluid and
      faecal samples were collected daily to Day 35 and thence twice weekly for
      measurement of serum gastrin and pepsinogen concentrations, blood eosinophils,
      abomasal pH and FEC. Abomasal worm counts were made after necropsy on Day 94.
      Skin biopsies were collected weekly for estimation of the percentage of wool
      follicles containing paracortical cells. Total serum immunoglobulin and IgG1,
      IgG2, IgA and IgM titres specific for T. circumcincta antigens were estimated
      twice weekly to Day 42 p.i., then weekly. After the primary challenge, FEC were
      higher in the HFW lambs, whereas neither group shed many eggs during the 5-week
      trickle infection; worm burdens were small at post mortem. Resilient HFW lambs
      showed a lesser inflammatory response, but relatively small differences in
      abomasal secretion. Circulating eosinophil counts increased moderately in both
      groups, less in the HFW lambs, during the primary infection and more markedly
      during the subsequent trickle infection, when the increase in the C lambs became
      significantly greater. All measured serum antibody titres were low in both groups
      throughout. Selection for HFW altered the wool characteristics of parasite-naive
      lambs (fewer follicles containing paracortical cells). There was a slower
      increase in the percentage of follicles containing these cells after primary
      infection. Abomasal function was similar in the two groups, both exhibiting
      typical increases in abomasal pH and serum gastrin and pepsinogen concentrations.
      The most marked differences in the HFW lambs were a greater rise in serum
      pepsinogen during the primary infection and the 2-day delay in onset of
      hypoacidity. Resilience to parasitism in this flock is consistent with
      maintenance of wool quality and small differences in abomasal secretion resulting
      from an attenuated immune response causing fewer detrimental effects on host
      tissues.

PMID- 19398277
TI  - Hydrocortisone reduces emotional distracter interference in working memory.
AB  - Several studies have shown that stress and glucocorticoids can impair prefrontal
      dependent working memory (WM) performance. WM is the ability to attend to the
      task at hand, and to maintain relevant information in mind during a delay while
      ignoring irrelevant stimuli. Here, it is investigated whether stress hormones
      impair WM by reducing the ability to suppress distracting, irrelevant neutral and
      emotional stimuli. Hydrocortisone (35 mg) (n=23) or placebo (n=21) was
      administered to young, healthy men, who performed a Sternberg WM task with
      neutral and emotional irrelevant distracters shown in the delay-phase of the
      task, between encoding and recognition of the relevant stimuli for WM. Contrary
      to expectations, enhanced WM performance with higher processing speed and a
      reduction of errors was found in the hydrocortisone group compared to placebo.
      Moreover, hydrocortisone significantly reduced the distraction by emotional
      stimuli. These findings show that cortisol effects on WM are not unambiguous and
      contrast with previous findings on the impairing effects of cortisol on WM. Dose
      response studies could give more insight into the specific modulating effects of
      glucocorticoids on suppression of irrelevant emotional distraction.

PMID- 19398278
TI  - The impact of parental modeling and permissibility on alcohol use and experienced
      negative drinking consequences in college.
AB  - This study examined the impact of parental modeled behavior and permissibility of
      alcohol use in late high school on the alcohol use and experienced negative
      drinking consequences of college students. Two-hundred ninety college freshmen at
      a large university were assessed for perceptions of their parents' permissibility
      of alcohol use, parents' alcohol-related behavior, and own experienced negative
      consequences associated with alcohol use. Results indicate that parental
      permissibility of alcohol use is a consistent predictor of teen drinking
      behaviors, which was strongly associated with experienced negative consequences.
      Parental modeled use of alcohol was also found to be a risk factor, with
      significant differences being seen across the gender of the parents and teens.
      Discussion focuses on risk factors and avenues for prevention research.

PMID- 19398280
TI  - Host melatonin secretion is a timing signal for the release of W. bancrofti
      microfilaria into the circulation.
AB  - Infection of the lymphatic system by Wuchereria bancrofti microfilaria is the
      most common cause of elephantiasis, a disease that affects over 100 million
      people. The nightly release of microfilaria into the circulation coincides with
      the feeding activity of its mosquito vector, a synchronization that is presumably
      an evolutionary adaptation favoring survival and transmission of the parasite.
      During the daytime hours, the microfilaria are thought to be sequestered in the
      lungs, and because they are not exposed to the solar light/dark cycle, there must
      be some other cue that entrains their nightly release into the periphery. I
      hypothesize that the host's secretion of melatonin synchronizes the nocturnal
      release of the microfilaria. It follows that exogenous melatonin administration
      during the day would also trigger release of microfilaria in the blood and could
      be used as a provocative diagnostic test for filariasis.

PMID- 19398279
TI  - Gender moderation and social developmental mediation of the effect of a family
      focused substance use preventive intervention on young adult alcohol abuse.
AB  - This study examined the long-term impact of Preparing for the Drug Free Years
      (PDFY) on young adult alcohol abuse disorder, addressing theory-based questions
      about how, and for whom, the program had its effects on the outcomes.
      Participants were 429 families of 6th graders enrolled in 33 rural schools
      located in the Midwestern United States. Schools were randomly assigned to
      conditions. Target adolescents (52% female) were interviewed periodically from
      age 11 to age 22; throughout adolescence, information was collected also from the
      youths' parents. Moderation and mediation analyses were conducted using
      regression analysis and structural equation modeling with covariates measured at
      baseline (age 11), mediators measured at posttest (age 12), and the outcome
      measured at the young adult follow-up (age 22). Results showed that PDFY reduced
      the rate of alcohol abuse among target young women, with evidence that this
      effect was mediated by increased prosocial skills. The rate of alcohol abuse
      among PDFY group men was not significantly different from that of control group
      men. Findings have implications for reducing the public health burden of alcohol
      abuse among young women.

PMID- 19398281
TI  - Surgical site marking will not affect sterility of the surgical field.
AB  - Surgical site marking has been recommended to prevent wrong site surgery (WSS).
      According to the Universal Protocol promulgated by the Joint Commission on
      Accreditation of Healthcare Organizations (JCAHO), the mark must be made using an
      indelible marker that is sufficiently permanent to remain visible after
      completion of the skin preparation. However, in clinical practice, one skin
      marker always is non-sterile and used on several patients. Therefore, in theory,
      there is a risk of contamination of the surgical site from a surgical marker. We
      hypothesize that the surgical site marking used by the marker which is non
      sterile and reused on multiple patients, may affect the surgical preparation and
      potentially contaminate the surgical field. After a review of the available
      evidences, we conclude that surgical site marking does not affect the sterility
      of the surgical field. Surgeons should be more confident in confirming
      preoperative marking as an effective component in preventing WSS.

PMID- 19398282
TI  - Alzheimer's disease and atherosclerosis: passers-by or brothers?
AB  - There seems to be little relationship between Alzheimer's disease and
      atherosclerotic disease for quite a long time. But current evidence from
      epidemiological, pathological, and clinical studies indicate an association of
      them both. We speculate that Alzheimer's disease and atherosclerosis are brothers
      but not passers-by, in molecule, especially in the light of interaction between
      reticulon 3(RTN3) and reticulon 4(RTN4B).

PMID- 19398284
TI  - Differences in preovulatory follicle dynamics and timing of preovulatory LH surge
      affect fertility of maiden sheep reared in semi-arid extensive conditions.
AB  - In the current study follicular dynamics, pituitary function, ovulatory response
      and luteal activity of 30 maiden Barbarine sheep were analyzed according to
      oestrus occurrence and lambing outcome after oestrus synchronisation with
      cloprostenol. Animals were retrospectively classified in three groups named as O-
      (n=7, ewes not displaying oestrus), O+L- (n=7, ewes showing oestrus but failing
      to lamb) and O+L+ (n=16; ewes showing oestrus and lambing thereafter). All the
      sheep ovulated and daily transrectal ultrasonographies revealed that preovulatory
      follicles were present at cloprostenol injection in all the animals. In sheep
      O+L+ and O+L-, 50% and 57% of the ovulatory follicles were the largest follicles
      at cloprostenol treatment (mean size of 4.1+/-0.26 mm and 4.3+/-0.74 mm,
      respectively). In O- ewes, the same percentage was higher (86%, P<0.05 when
      compared to group O+L+; mean size of 4.0+/-0.46 mm). The number of large
      follicles and the final diameter of the ovulatory follicles at oestrous tended
      thereafter to be higher in group O+L+ (1.4+/-0.1 and 6.4+/-0.2) than in groups
      O+L- (1+/-0.2 and 5.7+/-0.36) and O- (0.9+/-0.2 and 5.9+/-0.5, respectively).
      Conversely, the number of medium follicles at oestrus detection was higher in the
      group O+L- (2.1+/-0.3, P<0.05) than in the other two groups (1+/-0.2 and 1+/-0.3
      for O+L+ and O- respectively). Timing of preovulatory LH surge was earlier for
      ewes O- (24.0+/-4.75, P<0.05) than for sheep O+L+ and O+L- (37.9+/-2.45 h and
      38.0+/-4.75 h, respectively) and 94% of O+L+ ewes had a LH surge between 16 h and
      64 h after cloprostenol injection compared to 57% in O+L- and O- groups (P<0.05).
      Thus, maiden Barbarine sheep failing to display oestrus or conceive showed
      alterations in their follicular dynamics and, thereafter, pituitary function and
      ovulatory response.

PMID- 19398285
TI  - [Deficits in reading acquisition in primary school: cognitive, social and
      behavioral factors studied in a sample of 1062 children].
AB  - BACKGROUND: Reading impairment is the major learning disability in children.
      While research on illiteracy has mainly been conducted from a sociological
      perspective, research on dyslexia has typically been studied from a cognitive
      linguistic perspective. Studies that jointly investigate sociological, behavioral
      and cognitive factors in predicting reading outcome are rare and limited to
      English-speaking populations. The goal of the present study was to screen second
      grade children with reading impairment in French urban elementary schools and to
      pin down the factors that explain the various facets of reading failure and
      success. METHODS: A total of 1062 children from 20 different schools in the city
      of Paris participated in the study. Different aspects of reading were assessed
      individually for children with a suspected impairment in reading acquisition.
      Subsequently, 131 poor readers and 50 typically developing readers were matched
      for sex, age, and school. For these children, medical, cognitive, behavioral and
      individual socioeconomic data were obtained. Group differences were examined and
      multiple regression analyses were conducted to examine how much variance in
      reading was explained by the various variables. RESULTS: The prevalence of poor
      reading skills in grade 2 was highly influenced by neighborhood socioeconomic
      status (SES) (ranging from 3.3% in high SES to 20.5% in low SES areas). Among the
      SES variables, employment of the father was a significant predictor of poor
      reading. Among the cognitive variables, phonological awareness and rapid naming
      were the most significant factors, much more than verbal or nonverbal
      intelligence. Among the behavioral variables, attention was an important factor
      but not externalized symptoms. Multiple regression analyses showed that reading
      outcome was best predicted by phonological awareness skills and attention
      deficits. CONCLUSION: The majority of children with reading disability come from
      low SES areas. As in the English literature, the most robust predictor for
      reading impairment is phonological awareness, even when SES is taken into
      account. In addition, attention deficits seemed to aggravate reading impairments
      for children with weak phonological awareness skills. Successful early prevention
      should focus on reinforcing phonological awareness, recoding and attention
      skills.

PMID- 19398283
TI  - The GABA B agonist baclofen reduces cigarette consumption in a preliminary double
      blind placebo-controlled smoking reduction study.
AB  - The surge in dopamine in ventral striatal regions in response to drugs of abuse
      and drug-associated stimuli is a final common pathway of addiction processes.
      GABA B agonists exert their effects indirectly, by quieting dopaminergic
      afferents. The ability of the GABA B agonist, baclofen to ameliorate nicotine and
      drug motivated behavior is established within the animal literature, however its
      potential to do so in humans is understudied, particularly with respect to its
      possible utility as a smoking cessation agent. We conducted a nine-week double
      blind placebo-controlled pilot trial of baclofen for smoking reduction
      (N=30/group) in smokers contemplating, but not quite ready to quit. Baclofen was
      titrated upwards to 20mg q.i.d. over a period of twelve days. The primary outcome
      measure was the number of cigarettes smoked per day (CPD). A significant group by
      time effect of medication was observed. Baclofen was superior to placebo in
      reducing CPD (beta=0.01, t=1.97, p<0.05). The most common side effect reported
      during baclofen treatment is transient drowsiness, however there were no
      differences between groups in mild, moderate, or severe sedation. Craving was
      significantly lowered at end of treatment in all smokers (p<0.02). Retention did
      not differ between groups. In line with a multitude of preclinical studies
      examining the effects of baclofen on drug-motivated behavior, baclofen reduced
      CPD. In agreement with other studies examining craving and drug use, reductions
      in CPD were accompanied by a reduction in craving, a major motivator underlying
      continued smoking and relapse. These preliminary results demonstrate provisional
      evidence of the utility of baclofen to aid in smoking cessation and indicate
      further investigation.

PMID- 19398286
TI  - [Laboratory diagnosis of bacterial meningitis: usefulness of various tests for
      the determination of the etiological agent].
AB  - Despite breakthroughs in the diagnosis and treatment of infectious diseases,
      meningitis still remains an important cause of mortality and morbidity. An
      accurate and rapid diagnosis of acute bacterial meningitis is essential for a
      good outcome. The gold-standard test for diagnosis is CSF analysis. Gram staining
      of CSF reveals bacteria in about 50 to 80 % of cases and cultures are positive in
      at best 80 % of cases. However, the sensitivity of both tests is less than 50 %
      in patients who are already on antibiotic treatment. CSF leukocyte count and
      concentration of protein and glucose lack specificity and sensitivity for the
      diagnosis of meningitis. Other biological tests are available for the diagnosis.
      Latex agglutination test were adapted for rapid and direct detection of soluble
      bacterial antigens in CSF of patients suspected with bacterial meningitis. This
      test is efficient in detecting antigens of most common central nervous system
      bateria but lacks sensibility. Furthermore, in the early phases of acute
      bacterial and viral meningitis, signs and symptoms are often non specific and it
      is not always possible to make a differential diagnosis. Markers like CRP,
      procalcitonin, or sTREM-1 may be very useful for the diagnosis and to
      differentiate between viral and bacterial meningitis. Bacterial meningitis
      diagnosis and management require various biological tests and a multidisciplinary
      approach.

PMID- 19398287
TI  - [Antibiotic management of presumptive bacterial meningitis in adults (rational,
      methods, course, and follow-up)].
AB  - The annual incidence of community acquired meningitis ranges between 0.6 and four
      per 100,000 adults in industrialized countries. The most common causative
      bacteria are Streptococcus pneumoniae, Neisseria meningitidis, Listeria
      monocytogenes. The emergence of resistance to antibiotics, especially for S.
      pneumoniae, could explain the clinical failure of third generation cephalosporins
      used to treat adults with S. pneumoniae meningitis. The present therapeutic
      suggestions are more based on the extrapolation of an experimental model than on
      relevant clinical trials.

PMID- 19398288
TI  - [Indication of neuro-imaging for the initial management and the follow-up of
      acute community-acquired bacterial meningitis].
AB  - Lumbar puncture is the best way to prove bacterial meningitis. It should be
      performed without any delay if the diagnosis is suspected. Herniation is a rare
      complication of LP. CT is normal in most cases of purulent meningitis, including
      those complicated by a subsequent herniation; normal CT results does not mean
      that performing a LP is safe. Three main clinical features can help determine
      which patient is at risk of herniation and should have a CT before LP. This risk
      has to be determined rapidly in the emergency ward while assessing anamnestic
      data, localization signs or symptoms, and level of consciousness. Cranial imaging
      (mainly MRI) is useful in the course of bacterial meningitis. Patients who do not
      respond well to treatment or with atypical presentation, persistence of fever, or
      new neurological signs should undergo brain imaging; MRI and CT may identify
      subdural effusions, brain abscesses, empyemas, hydrocephaly, or brain parenchymal
      changes (cerebritis, infarction, hemorrhage). CT and MRI are useful to screen for
      an ENT cause of bacterial meningitis, and mandatory in case of pneumococcal
      meningitis. Numerous MRI sequences are useful to identify bacterial meningitis
      complications: SE T1 without and with gadolinium injection, SE T2, FLAIR,
      gradient-echo T2, diffusion weighted imaging, MR angiography.

PMID- 19398289
TI  - Natural history and therapeutic management of recurrent hepatocellular carcinoma
      after liver transplantation.
AB  - While the natural history and appropriate diagnostic and management practices are
      relatively well defined for hepatocellular carcinoma (HCC), data are scarce
      concerning the characteristic features and treatment modalities for recurrent HCC
      after liver transplantation. The time of recurrence appears to impact survival
      more significantly than localization, but to date, guidelines for therapeutic
      management of recurrent HCC have not been established. Data in the literature
      shows that late and unifocal recurrence has a better prognosis when treated by
      surgery or radiofrequency. In the event of early recurrence, surgery cannot be
      recommended due to the lack of evidence and the high risk of advanced disease.
      Systemic therapy can be discussed in a situation of multifocal recurrence.
      Proliferative signal inhibitors exhibit both immunosuppressive and
      antiproliferative properties and liver transplantation teams tend to introduce
      such treatment despite the lack of extensive data.

PMID- 19398290
TI  - The efficacy of intraperitoneal saline infusion for percutaneous radiofrequency
      ablation for hepatocellular carcinoma.
AB  - OBJECTIVE: To evaluated the efficacy and safety of radiofrequency ablation (RFA)
      with intraperitoneal saline infusion. BACKGROUND: Ultrasound-guided RFA is not
      always feasible due to the tumor location, possible adjacent tissue damage or
      poor sonographic identification. PATIENTS AND METHODS: Ultrasound-guided RFA with
      intraperitoneal saline infusion was performed in 116 patients between June 2001
      and March 2008. RESULTS: The overall technical feasibility of the intraperitoneal
      saline infusions was 90.5% (105 patients). The purposes of the intraperitoneal
      saline infusion were achieved in 100 patients (86.2%) by visualizing the tumor
      located in hepatic dome (47 patients), prevent adjacent organ damage (42
      patients) and withdrawing overlying omentum (10 patients). Complete ablation of
      tumor was accomplished in 102 patients (87.9%). Complications associated with the
      treatment occurred in seven patients (6.0%). There was no case of adverse event
      directly related to intraperitoneal saline infusion. CONCLUSIONS: Intraperitoneal
      saline infusion is an effective and safe procedure that can be used to overcome
      the current limitations of ultrasound-guided RFA.

PMID- 19398291
TI  - Integrated FDG-PET/CT vs. standard radiological examinations: comparison of
      capability for assessment of postoperative recurrence in non-small cell lung
      cancer patients.
AB  - PURPOSE: The purpose of this study was to prospectively and directly compare
      diagnostic capabilities of whole-body integrated FDG-PET/CT and standard
      radiologic examination for assessment of recurrence in postoperative non-small
      cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: A total of 92
      consecutive pathologically diagnosed NSCLC patients (65 males, 27 females; mean
      age, 71 years) underwent pathologically and surgically proven complete resection,
      followed by prospective whole-body FDG-PET/CT and standard radiological
      examinations. Final diagnosis of recurrence was based on the results of more than
      1 year of follow-up and/or pathological examinations. On both methods, the
      probability of recurrence was assessed in each patient by using a five-point
      visual scoring system, and the each final diagnosis was made by consensus between
      two readers. Kappa analyses were performed to determine inter-observer agreement
      for both methods, and ROC analyses were used to compare capability of the two
      methods for assessment of postoperative recurrence on a per-patient basis.
      Sensitivity, specificity and accuracy were also compared between PET/CT and
      standard radiological examination by means of McNemar's test. RESULTS: All inter
      observer agreements were almost perfect (integrated PET/CT: kappa=0.89; standard
      radiological examination: kappa=0.81). There were no statistically significant
      differences in area under the curve, sensitivity, specificity and accuracy
      between integrated FDG-PET/CT and standard radiologic examinations (p>0.05).
      CONCLUSION: Integrated FDG-PET/CT can be used for assessment of postoperative
      recurrence in NSCLC patients with accuracy as good as that of standard
      radiological examinations.

PMID- 19398292
TI  - HPLC-MS/MS method for the intracellular determination of ribavirin monophosphate
      and ribavirin triphosphate in CEM ss cells.
AB  - A sensitive and specific method using high performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS) for the determination of ribavirin
      monophosphate (RBV-MP) and ribavirin triphosphate (RBV-TP) in cells has been
      developed and validated. In this method, ribavirin phosphorylated metabolites
      were extracted and separated by anion exchange solid phase extraction (SPE). The
      RBV-MP and RBV-TP fractions were dephosphorylated using acid phosphatase and
      further purified by phenyl boronate SPE prior to HPLC-MS/MS analysis. (13)C(5)
      uridine was added as internal standard to obtain better accuracy and precision of
      the analysis. The MS/MS detector was optimized at multiple reaction monitoring
      (MRM) using positive electrospray ionization to detect 245-->113 and 250-->133
      transitions for ribavirin and internal standard, respectively. The calibration
      curve was linear over a concentration range of 0.01-10 microg/mL with a limit of
      quantitation of 0.01 microg/mL. Mean inter-assay accuracy and precision for RBV
      MP and RBV-TP quality control samples at 0.03, 0.3 and 8 microg/mL were 5% and
      10%, respectively. This method was successfully used for the in vitro
      determination of RBV-MP and RBV-TP in CEM(ss) cells cultured with RBV.

PMID- 19398293
TI  - Community mental healthcare providers' attitudes and practices related to smoking
      cessation interventions for people living with severe mental illness.
AB  - OBJECTIVE: This study aimed to describe mental healthcare providers' attitudes
      about tobacco use, their personal smoking status, their confidence in offering
      smoking cessation support to clients living with severe mental illness, and the
      extent to which they incorporated smoking cessation interventions into their
      practice. The study also aimed to determine whether the providers' attitudes,
      smoking status, and confidence were associated with offering smoking cessation
      support to clients. METHODS: Self-administered questionnaires were distributed
      within community-based mental health agencies to those who provide care and
      support to adults living with severe mental illness. Outcomes measured included
      respondents' smoking status, attitudes related to the provision of smoking
      cessation support, confidence in providing smoking cessation intervention, and
      smoking cessation practices. We conducted multivariate analyses using logistic
      regression analyses to examine the factors associated with the providers' tobacco
      related practices. RESULTS: In total 282 of 871 care providers responded to the
      survey, 22% of whom were current smokers. The providers who held sympathetic
      attitudes about their role and their clients' role in smoking cessation, who were
      never or former smokers, who were healthcare professionals rather than
      paraprofessionals, who had relatively more confidence, and who had more
      experience working in the mental health field were more likely to engage their
      clients in tobacco-related interventions. CONCLUSIONS: In this study the
      healthcare providers working in community-based mental health have a smoking
      prevalence rate that exceeds that of the region's general population and did not
      provide optimal smoking cessation support to their clients. PRACTICE
      IMPLICATIONS: Interventions that bolster the confidence of providers to engage is
      smoking cessation activities and that support a shift in attitudes about the role
      of tobacco use in mental health are required.

PMID- 19398294
TI  - [Essential thrombocythemia presenting as spinal cord infarction].

PMID- 19398295
TI  - The Bayesian interpretation of a P-value depends only weakly on statistical power
      in realistic situations.
AB  - OBJECTIVE: It is often repeated that a low P-value provides more persuasive
      evidence for a genuine effect if the power of the test is high. However, this is
      based on an argument which ignores the precise P-value in favor of simply
      observing whether P is less than some cut-off, and which oversimplifies the
      possible effect sizes. In a non-Bayesian framework, there are good reasons to
      think that power does not affect the evidence of a given P-value. Here I
      illustrate the relationship between pre-study power and the Bayesian
      interpretation of a P-value in realistic situations. STUDY DESIGN AND SETTING: A
      Bayesian calculation, using a conventional prior distribution for the effect size
      and a normal approximation to the sampling distribution of the sample estimate,
      where the datum is the precise P-value. RESULTS: Over the range of pre-study
      powers typical in published research, the Bayesian interpretation of a given P
      value varies little with power. CONCLUSION: A Bayesian analysis with reasonable
      assumptions produces results remarkably in line with a more simple, non-Bayesian
      intuition-that the evidence against the null hypothesis provided by a precise P
      value should not depend on power.

PMID- 19398296
TI  - The STRATIFY tool and clinical judgment were poor predictors of falling in an
      acute hospital setting.
AB  - OBJECTIVE: To compare the effectiveness of the STRATIFY falls tool with nurses'
      clinical judgments in predicting patient falls. STUDY DESIGN AND SETTING: A
      prospective cohort study was conducted among the inpatients of an acute tertiary
      hospital. Participants were patients over 65 years of age admitted to any
      hospital unit. Sensitivity, specificity, and positive predictive value (PPV) and
      negative predictive values (NPV) of the instrument and nurses' clinical judgments
      in predicting falls were calculated. RESULTS: Seven hundred and eighty-eight
      patients were screened and followed up during the study period. The fall
      prevalence was 9.2%. Of the 335 patients classified as being "at risk" for
      falling using the STRATIFY tool, 59 (17.6%) did sustain a fall (sensitivity=0.82,
      specificity=0.61, PPV=0.18, NPV=0.97). Nurses judged that 501 patients were at
      risk of falling and, of these, 60 (12.0%) fell (sensitivity=0.84,
      specificity=0.38, PPV=0.12, NPV=0.96). The STRATIFY tool correctly identified
      significantly more patients as either fallers or nonfallers than the nurses
      (P=0.027). CONCLUSION: Considering the poor specificity and high rates of false
      positive results for both the STRATIFY tool and nurses' clinical judgments, we
      conclude that neither of these approaches are useful for screening of falls in
      acute hospital settings.

PMID- 19398297
TI  - Associating explanatory variables with summary receiver operating characteristic
      curves in diagnostic meta-analysis.
AB  - OBJECTIVE: To show how the bivariate random effects meta-analysis model can be
      used to study the relation between the explanatory variables and the performance
      of diagnostic tests as characterized by a summary receiver operating
      characteristic curve (SROCC). STUDY DESIGN AND SETTING: The subject is discussed
      by means of a data example in which sensitivity and specificity are available for
      149 studies on one of three tests for the diagnosis of coronary artery disease.
      The focus is on comparing SROCCs between different tests adjusted for potential
      confounders, but the methods can be applied much more generally. RESULTS:
      Different types of SROCCs can be calculated. The influence of explanatory
      variables on an SROCC is an ensemble of sensitivity and specificity regression
      coefficients and covariance parameters. The regression coefficients of the SROCC
      are estimated and tested, and the percentage explained variability is determined.
      Under certain assumptions, the SROCCs of different covariate values do not cross.
      If these are fulfilled, it is much easier to describe the influence of
      explanatory variables. Conclusions can depend on the type of SROCC. CONCLUSION:
      The bivariate random effects meta-analysis model is an appropriate and convenient
      framework to investigate the effect of covariates on the performance of
      diagnostic tests as measured by SROCCs.

PMID- 19398298
TI  - Adjusting weighted kappa for severity of mistriage decreases reported reliability
      of emergency department triage systems: a comparative study.
AB  - OBJECTIVE: Mistriage can have serious consequences for patients with urgent
      complaints. We therefore reviewed the assessment of triage-reliability, and
      propose an alternative weighted kappa that accounts for severity of mistriage.
      STUDY DESIGN AND SETTING: A systematic literature search was performed in three
      online databases and a search engine. An alternative kappa weighting scheme was
      developed (triage-weighted kappa), and kappas of previous conducted reliability
      studies were recalculated. RESULTS: Kappa is the most frequently used statistic
      in triage-reliability studies (n=33). More than half of the studies did not
      report the type of kappa that was used. Linear and quadratically weighted kappa
      values do not reflect the seriousness of mistriage. Several studies reported
      almost perfect agreement, whereas percentages of mistriage ranged between 11.1%
      and 43.4%. In all studies, triage-weighted kappa was lower than reported kappas
      with a mean difference of 0.17 (range: 0.04-0.32). CONCLUSION: No existing
      studies on reliability of triage systems account for mistriage. Using triage
      weighted kappa, which reflects severity of mistriage, shows that the reliability
      of triage systems is lower than reported.

PMID- 19398300
TI  - Effects of curcuminoid supplement on cardiac autonomic status in high-fat-induced
      obese rats.
AB  - OBJECTIVE: Sudden cardiac death in obesity is frequently associated with
      sympathetic activation due to an elevated plasma free-fatty acid (FFA) level.
      Curcuminoids, the phenolic yellowish pigments of turmeric, display antioxidative
      and lipid-lowering activities. We hypothesized that curcuminoids ameliorate
      cardiac sympathovagal disturbance in high-fat-induced obese rats. METHODS: Male
      Wistar rats were divided into five groups. A normal-diet control (NDC) group
      received a normal-fat diet (12% calories as fat) and a high-fat-diet control
      (HDC) group received a high-fat diet (60% calories as fat) for 12 wk. Three other
      groups received high-fat diets with curcuminoid supplement at concentrations of
      30mg (HD(30)), 60mg (HD(60)), and 90mg (HD(90)) per kilogram of body weight every
      day for 12 wk. Heart rate variability was determined to assess cardiac autonomic
      status at weeks 0 and 12. RESULTS: Body weight, visceral fat mass, plasma FFA,
      and glucose levels increased significantly in the HDC group compared with the NDC
      group. Low frequency power in normalized units (LFnu) and the ratio of LF to high
      frequency power (HF) in the HDC group were significantly higher, whereas HFnu in
      the HDC group was significantly lower than in the NDC group. Plasma FFA levels
      correlated significantly with LFnu and LF/HF ratio. Compared with the HDC group,
      plasma FFA, glucose levels, LFnu, and LF/HF ratio were significantly decreased in
      the HF(30), HF(60), and HF(90) groups. CONCLUSION: Elevated plasma FFA in high
      fat-induced obese rats is associated with an increased LF/HF ratio, an expression
      of sympathovagal disturbance. Curcuminoid supplementation ameliorates cardiac
      autonomic imbalance in high-fat-fed rats, probably due to its lipid-lowering
      effect.

PMID- 19398299
TI  - Synergistic interactions of antioxidant nutrients in a biological model system.
AB  - OBJECTIVE: The antioxidant activity of fat- and water-soluble antioxidant
      nutrients and their interactions in physiologic concentrations were determined in
      an in vitro biological model system. METHODS: Reconstituted human serum
      consisting of delipidized human serum (DHS) combined with phosphatidylcholine
      liposomes (PCL) was used to determine antioxidant activities of physiologic
      concentrations of antioxidant nutrients. Radicals were initiated with 2,2'
      azobis(4-methoxy-2,4-dimethylvaleronitrile) (2mmol/L), and oxidation was
      monitored by 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s
      indacene-3-undecanoic acid. Fat-soluble antioxidant nutrients were incorporated
      into the PCL prepared by sonication and suspended in DHS to avoid any
      interference by the endogenous fat-soluble antioxidants. Water-soluble
      antioxidants were added directly into the DHS. The oxidation kinetics were
      monitored every 5 min up to 210 min using a microplate reader (excitation
      wavelength 500 nm, emission wavelength 520 nm). RESULTS: We confirmed the
      synergistic protective effect of the combination of ascorbic acid (1-5 microM)
      and alpha-tocopherol (1-5 mircoM) against the oxidation of DHS with PCL.
      Furthermore, physiologic concentrations of 1) beta-carotene (0.1, 0.5 microM) and
      alpha-tocopherol (2.5, 5.0 microM), 2) beta-carotene (0.1, 0.5 microM) and
      ascorbic acid (2.5 microM), and 3) uric acid (10 uM) and alpha-tocopherol (2.5,
      5.0 microM) synergistically protected oxidation of reconstituted human serum.
      CONCLUSION: The present study results suggest a wide antioxidant network between
      water- and fat-soluble antioxidant nutrients in a biological system, although
      their actions in vivo warrant further study.

PMID- 19398302
TI  - Validity of the Spanish version of the Personal and Social Performance scale in
      schizophrenia.
AB  - BACKGROUND: The Personal and Social Performance (PSP) scale is a reliable and
      valid instrument that utilizes objective parameters for the assessment of social
      functioning in patients with schizophrenia. OBJECTIVE: The aim of this study was
      to determine the validity and reliability of the Spanish version of the PSP
      scale. METHOD: In total, 100 patients with DSM-IV diagnoses of schizophrenia and
      schizoaffective disorder were recruited and assessed with the PSP, the GAF, the
      PANSS, and the CGI. Internal consistency for the PSP was obtained and
      discriminant validity was assessed by comparing PSP scores between inpatients and
      outpatients; correlations between PSP scores, the GAF, and the five factors of
      the PANSS were used to evaluate the convergent validity of the scale; reliability
      was evaluated with intra-class correlation coefficients and temporal stability
      was obtained using correlation coefficients between the PSP and CGI scores on a
      follow up assessment. RESULTS: The Cronbach's alpha coefficient of the PSP was
      0.843. Inpatients showed lower scores on the PSP than did outpatients. Patients
      with low scores on the PSP reported fewer years of education, were more
      frequently unemployed, had a longer duration of illness, and had a shorter
      duration of antipsychotic treatment. The PSP scores showed a positive correlation
      with the GAF and a negative correlation with the cognitive, negative, and
      positive factors derived from the PANSS. The PSP scores showed significant
      correlations with the severity and improvement CGI scores at follow-up. Good
      inter-rater reliability was obtained. CONCLUSION: These findings support the
      Spanish version of PSP to be a reliable and valid instrument for the assessment
      of social functioning in patients with schizophrenia.

PMID- 19398301
TI  - Unaffected motor cortex remodeling after hemispherectomy in an epileptic cerebral
      palsy patient. A TMS and fMRI study.
AB  - PURPOSE: Here we describe pre- and post-operative neurophysiological and
      functional magnetic resonance imaging (fMRI) findings in a young epileptic girl
      with right hemiplegic cerebral palsy. Our findings demonstrate the feasibility of
      transcranial magnetic stimulation (TMS) and fMRI for predicting a post-surgical
      outcome and for evaluating functional cortical reorganization. METHODS: We used
      TMS and fMRI to evaluate the excitability of the human motor cortex and cortical
      map representation before and after functional hemispherectomy. TMS was performed
      using single- and paired-pulse stimulation protocol. Cortical silent periods
      (CSPs), short interval intra-cortical inhibition (SICI), volume, area and center
      of gravity (CoG) of cortical map representation were studied before and after
      surgery. fMRI was done using the blood oxygenation level dependent (BOLD)
      technique with block-designed protocols. RESULTS: After surgery the patient
      showed an improvement of her clinical status and TMS and fMRI demonstrated a
      reshaping of cortical representation of motor cortex and a significant reduction
      of cortical silent periods. DISCUSSION: Before surgery, the combination of a
      clinical, neurophysiological and neuro-radiological approach may be predictable
      of the neurological outcome in epileptic patients. Moreover, the patient we
      describe provides new pieces of information in the mechanisms of plasticity
      underlying motor recovery after epilepsy surgery.

PMID- 19398303
TI  - Impact of changing the Japanese term for "schizophrenia" for reasons of
      stereotypical beliefs of schizophrenia in Japanese youth.
AB  - The old term for schizophrenia, "Seishin-Bunretsu-Byo" (Mind-Split Disease), has
      been replaced by "Togo-Shitcho-Sho" (Integration Disorder) in Japan. Stigma
      research requiring individuals to report personal beliefs is useful but is
      subject to social desirability bias. Using the Implicit Association Test, a
      measurement designed to minimize this bias, we assessed the impact of this
      renaming on the stereotype of schizophrenia held by a younger generation. The old
      term was strongly associated with "criminal", and this association became
      significantly weaker with the new term. The strategy of renaming holds
      considerable promise for tempering negative bias toward this disorder in Japan.

PMID- 19398305
TI  - Greeting from the President of the Japanese Society for Investigative Dermatology
      (JSID): on achieving internationalization and educating young researchers.

PMID- 19398304
TI  - Familial aggregation of clinical and neurocognitive features in sibling pairs
      with and without schizophrenia.
AB  - OBJECTIVE: Neurocognitive impairment was found to be heritable in individuals
      with schizophrenia and their relatives. However, the heritability of
      neurocognitive measures in families with and without schizophrenia has not been
      directly compared. In this study, we examined the genetic structure of clinical
      and neurocognitive measures in sibling pairs with and without schizophrenia to
      test the hypothesis that the familial aggregation of such measures may be altered
      by having schizophrenia. METHOD: A total of 278 subjects including patients with
      schizophrenia and their non-psychotic full siblings, healthy controls, and their
      full siblings were recruited. Heritability was estimated for working memory,
      episodic memory, executive function and attention, as well as clinical features,
      such as positive, negative and disorganization symptoms. RESULTS: Many clinical
      and cognitive domains were impaired in subjects with schizophrenia and their non
      psychotic siblings. Negative symptoms, working memory, episodic memory and
      executive function, but not positive, disorganization symptoms and attention,
      were found to be significantly heritable in all sibling pairs. However, the
      heritability of working memory function was significantly (chi(2)((d.f.=6))=13.9,
      p=.031) decreased in proband sibling pairs (h(2)=.38) as compared to control
      sibling pairs (h(2)=.95). Significant genetic correlations were observed between
      negative symptoms and the cluster of working memory, episodic memory and
      executive function. CONCLUSIONS: Several neurocognitive measures were heritable
      in sibling pairs with and without schizophrenia. However, schizophrenia reduced
      the heritability of working memory, perhaps due to disease-related environmental
      or genetic factors. Evidence for potential pleiotropy will inform future
      phenotypic studies.

PMID- 19398306
TI  - Photodynamic therapy using a novel photosensitizer, EC036, is more effective
      compared with ATX-S10(Na) photodynamic therapy.

PMID- 19398307
TI  - Structural development of the basal ganglia in attention deficit hyperactivity
      disorder: a diffusion tensor imaging study.
AB  - One of the most consistently reported brain regions of structural and functional
      difference in attention deficit hyperactivity disorder (ADHD) is the basal
      ganglia, particularly the caudate nucleus. Examining the structural organization
      of the basal ganglia in ADHD is important because it is the center of wider
      fronto-striatal networks, reported to be dysfunctional in ADHD. Fifteen right
      handed 8- to 18-year-old males with ADHD-combined type and 15 right-handed, age-
      and performance IQ-matched healthy males underwent diffusion tensor imaging.
      Caudate, putamen and thalamus were manually identified as regions of interest
      (ROIs) and tested for differences in fractional anisotropy and mean diffusivity.
      Measures of fractional anisotropy (FA) showed the expected increase with age
      within the whole-brain volume and within putamen and thalamus ROIs for both ADHD
      and control groups. In the caudate nucleus, however, developmental changes in FA
      with age were significantly different between ADHD and control groups. This study
      shows that the developmental trajectory of micro-structural organization within
      the caudate nucleus is different in children with ADHD compared with controls
      over ages 8-18 years. We suggest that the difference in developmental
      trajectories arises predominantly during mid-late adolescence and may reflect a
      developmental delay that begins to normalise over this critical late adolescent
      age.

PMID- 19398308
TI  - Functional connectivity reveals inefficient working memory systems in post
      traumatic stress disorder.
AB  - We applied a covariance-based multivariate analysis to functional magnetic
      resonance imaging (fMRI) data to investigate abnormalities in working memory (WM)
      systems in patients with post-traumatic stress disorder (PTSD). Patients (n=13)
      and matched controls (n=12) were scanned with fMRI while updating or maintaining
      trauma-neutral verbal stimuli in WM. A multivariate statistical analysis was used
      to investigate large-scale brain networks associated with these experimental
      tasks. For the control group, the first network reflected brain activity
      associated with WM updating and principally involved bilateral prefrontal and
      bilateral parietal cortex. Controls' second network was associated with WM
      maintenance and involved regions typically activated during storage and rehearsal
      of verbal material, including lateral premotor and inferior parietal cortex. In
      contrast, PTSD patients appeared to activate a single fronto-parietal network for
      both updating and maintenance tasks. This is indicative of abnormally elevated
      activity during WM maintenance and suggests inefficient allocation of resources
      for differential task demands. A second network in PTSD, which was not activated
      in controls, showed regions differentially activated between WM tasks, including
      the anterior cingulate, medial prefrontal cortex, fusiform and supplementary
      motor area. These activations may be linked to hyperarousal and abnormal
      reactivity, which are characteristic of PTSD.

PMID- 19398310
TI  - Disturbance of the immune system by electromagnetic fields-A potentially
      underlying cause for cellular damage and tissue repair reduction which could lead
      to disease and impairment.
AB  - A number of papers dealing with the effects of modern, man-made electromagnetic
      fields (EMFs) on the immune system are summarized in the present review. EMFs
      disturb immune function through stimulation of various allergic and inflammatory
      responses, as well as effects on tissue repair processes. Such disturbances
      increase the risks for various diseases, including cancer. These and the EMF
      effects on other biological processes (e.g. DNA damage, neurological effects,
      etc.) are now widely reported to occur at exposure levels significantly below
      most current national and international safety limits. Obviously, biologically
      based exposure standards are needed to prevent disruption of normal body
      processes and potential adverse health effects of chronic exposure. Based on this
      review, as well as the reviews in the recent Bioinitiative Report
      [http://www.bioinitiative.org/] [C.F. Blackman, M. Blank, M. Kundi, C. Sage, D.O.
      Carpenter, Z. Davanipour, D. Gee, L. Hardell, O. Johansson, H. Lai, K.H. Mild, A.
      Sage, E.L. Sobel, Z. Xu, G. Chen, The Bioinitiative Report-A Rationale for a
      Biologically-based Public Exposure Standard for Electromagnetic Fields (ELF and
      RF), 2007)], it must be concluded that the existing public safety limits are
      inadequate to protect public health, and that new public safety limits, as well
      as limits on further deployment of untested technologies, are warranted.

PMID- 19398309
TI  - Encoding deficit during face processing within the right fusiform face area in
      schizophrenia.
AB  - Face processing is crucial to social interaction, but is impaired in
      schizophrenia patients, who experience delays in face recognition, difficulties
      identifying others, and misperceptions of affective content. The right fusiform
      face area plays an important role in the early stages of human face processing
      and thus may be affected in schizophrenia. The aim of the study was therefore to
      investigate whether face processing deficits are related to dysfunctions of the
      right fusiform face area in schizophrenia patients compared with controls. In a
      rapid, event-related functional magnetic resonance imaging (fMRI) design, we
      investigated the encoding of new faces, as well as the recognition of newly
      learned, famous, and unfamiliar faces, in 13 schizophrenia patients and 21
      healthy controls. We applied region of interest analysis to each individual's
      right fusiform face area and tested for group differences. Controls displayed
      higher blood oxygenation level dependent (BOLD) activation during the
      memorization of faces that were later successfully recognized. In schizophrenia
      patients, this effect was not observed. During the recognition task,
      schizophrenia patients exhibited lower BOLD responses, less accuracy, and longer
      reaction times to famous and unfamiliar faces. Our results support the hypothesis
      that impaired face processing in schizophrenia is related to early-stage deficits
      during the encoding and recognition of faces.

PMID- 19398311
TI  - [Soft tissue tumors in neonates].
AB  - Soft tissue tumors account for approximately 25% of neonatal tumors and are most
      often benign (more than 2/3 of cases). Vascular tumors are the most frequent
      benign tumors and infantile hemangioma accounts for 32% of these tumors,
      affecting 1 out of 200 children at birth. Kaposiform hemangioendothelioma (KH) is
      a rare vascular tumor with locally aggressive behavior. More than 50% of KH are
      associated with the Kasabach-Merritt phenomenon, a condition characterized by
      thrombocytopenia and consumptive coagulopathy. Malignant soft tissue tumors are,
      after neuroblastoma, the second cause of cancer in neonates. Infantile
      fibrosarcoma (IF) is a rare tumor that most often affects the extremities of
      children aged 4 years or younger. A recurrent t(12;15) (p13;q25) rearrangement
      fusing the ETV6 gene with the NTRK3 neurotrophin-3 receptor gene has been
      identified in IF. Complete conservative surgical resection is usually curative.
      Chemotherapy is indicated when initial surgical removal cannot be accomplished
      without unacceptable morbidity. Prognosis of IF is excellent, with reported
      overall survival rates ranging from 80 to 100%. Neonatal rhabdomyosarcoma (RMS)
      is a rare tumor (0.5-1% of RMS). The primary tumor predominantly involves the
      limbs and the genitourinary tract. Treatment is based on age-adapted chemotherapy
      and surgery. Prognosis of RMS in children less than 1 year old appears to be
      comparable with that of older children.

PMID- 19398312
TI  - Efficacy of photodynamic therapy as a treatment for Gorlin syndrome-related basal
      cell carcinomas.
AB  - AIMS: The management of the multiple basal cell carcinomas (BCCs) that develop
      throughout life of patients with Gorlin syndrome can be challenging. Surgical
      excision can result in significant disfigurement from scarring and tissue
      defects. Radiotherapy is contraindicated because of enhanced radiation
      tumourigenesis in these patients. Photodynamic therapy (PDT) is a simple,
      repeatable out-patient procedure, which is associated with minimal skin
      deterioration. It is now routinely used to treat superficial sporadic BCCs, using
      a topically-applied photosensitiser and external light, but its role in the
      management of Gorlin syndrome-related BCCs has yet to be established. In
      particular, Gorlin syndrome is often associated thick, nodular lesions which can
      be resistant to treatment with topical PDT. MATERIALS AND METHODS: We report our
      outcome data for 33 Gorlin patients (138 lesions) treated with PDT. Lesion
      thicknesses were assessed using ultrasound, both prior to treatment and during
      follow-up, to quantify treatment response and to guide the choice of treatment
      methods. Topical PDT was used to treat superficial lesions (<2 mm thick) and a
      systemic photosensitiser +/- light delivered by interstitially-placed optical
      fibres was employed for thicker lesions (>2 mm). RESULTS AND CONCLUSIONS: Local
      control rates of 56.3% at 12 months were achieved overall. The use of a systemic
      photosensitiser +/- interstitial light delivery extended the remit of PDT,
      allowing thicker lesions (>2 mm) to be treated, resulting in local control rates
      of 59.3% in this group. PDT can be considered as a treatment option for patients
      with multiple BCCs as a result of Gorlin syndrome. The use of ultrasound to
      accurately assess lesion thickness helps to select the optimum treatment method.
      Systemic photosensitisers and interstitial optical fibres can be used to treat
      thicker lesions, offering a treatment option for patients with thick nodular
      tumours who wish to avoid surgery.

PMID- 19398313
TI  - Protective effects of nigella sativa against gentamicin-induced nephrotoxicity in
      rats.
AB  - The aim of this study was focused on investigating the possible protective effect
      of NS against GS-induced nephrotoxicity. Twenty four Wistar-albino rats were
      divided into four equal groups as follows: control group, GS group (100mg/kg
      intraperitoneal - i.p.), NSL+GS group (0.2 ml/kg+100mg/kg i.p.) and NSH+GS group
      (0.4 ml/kg+100mg/kg i.p.). Plasma creatinine and urea levels significantly
      increased as a result of nephrotoxicity in the GS group. Also, creatinine and
      urea levels significantly decreased in NSL+GS and NSH+GS groups. In the GS group,
      plasma MDA and NO levels increased significantly (p<0.05) and erythrocyte SOD and
      GSH-Px activities decreased significantly (p<0.05) when compared with control
      group. NS administration with GS injection resulted in significantly decreased
      MDA and NO generation and increased SOD and GSH-Px activities when compared with
      GS group. Proximal tubular necrosis, vacuolation, desquamation and degeneration
      in epithelial cells of the proximal tubules, hyaline casts in tubular lumen,
      mononuclear cell infiltration, glomerular and basement membrane alterations were
      histopathologically detected in the kidneys of the GS group. Co-treatments with
      NS (low and high dose) considerably decreased the renal damage when compared with
      the GS group. In conclusion, NS acts in the kidney as a potent scavenger of free
      radicals to prevent the toxic effects of GS both in the biochemical and
      histopathological parameters.

PMID- 19398314
TI  - WITHDRAWN: A publisher's note to "Novel cyclin-dependent kinase (CDK1/2)
      inhibitor induced retinopathy in CD1 and B6C3F1 mice"
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- 19398315
TI  - Potential of nitrogen gas (N2) to control psychrotrophs and mesophiles in raw
      milk.
AB  - Pure N(2) gas was introduced in the headspace of test bottles containing raw milk
      that were then stored at either 6.0, 7.0, or 12.0 degrees C. Treatment with N(2)
      significantly reduced the growth of total bacteria, and the growth of bacterial
      subgroups such as psychrotrophs, enterobacteria, protease- and lipase-producing
      bacteria, and Listeria spp, and completely excluded Bacillus cereus growth on MYP
      plates. The inhibitory effect was maximal at 6.0 degrees C, and bacterial growth
      could be halted at this temperature for 11 days. At 12.0 degrees C, N(2) was able
      to inhibit growth during the first 48 h. No alarming or undesirable effects, such
      as the excessive growth of anaerobes or lactobacilli, were observed during the
      course of the study. The same treatments also halted the growth of one bacterial
      isolate in pure culture that expressed multiresistance to antibiotics. The
      continuous flushing of raw milk with pure N(2) gas in a so-called open system
      that allows gas exchanges with the environment positively impacted the
      microbiological quality of the raw milk at a temperature range of 6.0-12.0
      degrees C. This procedure should therefore be considered as a possible
      complementary method to refrigeration in controlling bacterial growth and the
      spoilage potential of both psychrotrophs and mesophiles in raw milk.

PMID- 19398316
TI  - Asthma patients' self-reported behaviours toward inhaled corticosteroids.
AB  - BACKGROUND: Patient adherence to recommended use of ICS is questionable in
      asthma, with irregular use or interruptions occurring frequently. Factors
      explaining discontinuation of controller therapy could orientate interventions.
      The characteristics of patients with interruptions of inhaled corticosteroids
      (ICSs), intentional or accidental, were investigated. METHODS: Asthma patients
      regularly prescribed ICS by GPs (Cegedim network) were included. Patients'
      characteristics and behaviours toward ICS (accidental/intentional interruptions,
      less frequent use of ICS and change in dosing) were identified from self-report
      questionnaires, and linked to data prescription database. Interrelations between
      declared behaviours toward ICS were studied with a Multiple Component Analysis
      (MCA) and the correlates of ICS interruptions were identified. RESULTS: During
      the past 3 months, 31.6% of 204 patients (mean age: 53.8 years, females: 59.3%)
      intentionally interrupted ICS when feeling better, 25.4% forgot ICS and 18.3%
      deliberately changed the doses. A quarter of patients considered constant use of
      respiratory medicines as unhealthy. MCA revealed that intentional, accidental
      interruptions and less frequent use of ICS were closely correlated. Risk of
      intentional interruption was increased when patients considered constant use of
      respiratory therapy to be unhealthy (OR=3.36, 95%CI=[1.47-7.66]). Conversely,
      risk was significantly lower when ICS was associated or combined with another
      controller (OR=0.24, 95%CI=[0.08-0.73]), compared to ICS in monotherapy. Less
      frequent interruptions were observed in patients older than 65 (OR=0.35,
      95%CI=[0.13-0.89]). CONCLUSIONS: Our study suggests that discontinuation of use
      of controllers is associated with other inadequate behaviours or beliefs about
      inhaled controllers. Efforts should be targeted at patients' perceptions and
      behaviours toward controller therapy.

PMID- 19398317
TI  - Solid health care waste management status at health care centers in the West Bank
      -Palestinian Territory.
AB  - Health care waste is considered a major public health hazard. The objective of
      this study was to assess health care waste management (HCWM) practices currently
      employed at health care centers (HCCs) in the West Bank--Palestinian Territory.
      Survey data on solid health care waste (SHCW) were analyzed for generated
      quantities, collection, separation, treatment, transportation, and final
      disposal. Estimated 4720.7 m(3) (288.1 tons) of SHCW are generated monthly by the
      HCCs in the West Bank. This study concluded that: (i) current HCWM practices do
      not meet HCWM standards recommended by the World Health Organization (WHO) or
      adapted by developed countries, and (ii) immediate attention should be directed
      towards improvement of HCWM facilities and development of effective legislation.
      To improve the HCWM in the West Bank, a national policy should be implemented,
      comprising a comprehensive plan of action and providing environmentally sound and
      reliable technological measures.

PMID- 19398318
TI  - Thermogravimetric analysis and kinetic study on large particles of printed
      circuit board wastes.
AB  - Pyrolysis of large printed circuit board (PCB) waste particle was conducted on a
      specially designed laboratory-scale thermobalance (Macro-TG) with sample loading
      of 30 g under dynamic nitrogen atmosphere. The effects of heating rate (10, 15,
      20 and 25 degrees C min(-1)) and particle size (1 mm x 1 mm, 5 mm x 5 mm, 10 mm x
      10 mm and 10 mm x 20 mm) were examined. To compare the different decomposition
      behavior of fine and large one, the thermal decomposition of PCB waste powder
      (approximately 5mg) was also performed on a thermogravimetric analyzer (common
      TG) under various heating rates (10, 15, 20 and 40 degrees C min(-1)) and
      particle size ranges (0.198-0.165 mm, 0.165-0.074 mm, 0.074-0.055 mm and 0.055
      0.047mm). Experimental results show that large particle has a pyrolysis reaction
      retardancy compared to fine one. The distributed activation energy model was used
      to study the pyrolysis kinetics. It was found that during pyrolysis process,
      values of frequency factor (k(0)) changed with different activation energy (E)
      values. On common TG, the E values range from 156.95 to 319.37 kJ mol(-1) and
      k(0) values range from 2.67 x 10(13) to 2.24 x 10(27)s(-1). While, on Macro-TG,
      the range of E was 31.48-41.26 kJ mol(-1) and of the frequency factor was 19.80
      202.67s(-1).

PMID- 19398319
TI  - Review of recycling performance indicators: a study on collection rate in Taiwan.
AB  - The Taiwan Environmental Protection Administration (Taiwan EPA) launched a
      national Extended Producer Responsibility (EPR) system after integrating eight
      private recycling organizations in 1998. After that, the environmental
      performance of the EPR system brought a lot of attention to policy makers. Many
      studies show positive environmental effects of the EPR system in Taiwan. However,
      there are controversial questions remained, such as whether the performance
      indicators used are the right choice to estimate the environmental effects of the
      recycling policy? Can those estimated results really reflect the performance of
      the system? This paper would therefore like to more accurately evaluate the
      performance indicators of the EPR system based on data observed over the past
      decade in Taiwan. In the process of evaluating the performance indicators, we
      have found that the collection rates for durable goods are often ignored in
      countries that pursue a zero waste policy. This may affect the actual recycling
      outcome and resource direction targeted by producers. However, in order for the
      collection rate to be adopted as a policy indicator, how to estimate the amounts
      of retired or waste products during a period is critical. In this paper, we
      estimate the collection rate for electrical and electronic waste by using the
      survival analysis and ownership data analysis approaches. We also provide a
      comparison of both approaches and put forward suggestions for directions in the
      future in solid waste management.

PMID- 19398320
TI  - Microbial oxygen uptake in sludge as influenced by compost physical parameters.
AB  - The wide range of optimal values reported for the physical parameters of compost
      mixtures suggest that their interactive relationships should be investigated. The
      objective of this study was to examine the microbial O(2) uptake rate (OUR) in 16
      sludge waste recipes, offering a range of moisture content (MC), waste/bulking
      agent (W/BA) ratio and BA particle size levels determined using a central
      composite experimental design. The 3 kg samples were maintained at a constant
      temperature and aeration rate for 28 days, during which a respirometer recorded
      O(2) uptake to provide a measure of microbial activity and biodegradability. The
      cumulative O(2) consumption after 14 and 28 days was found to be significantly
      influenced by MC, W/BA ratio, BA particle size and the interaction between MC and
      W/BA ratio (p<0.05). Using multivariate regression analysis, the experimental
      data was used to generate a model with good predictive ability for cumulative
      O(2) consumption after 28 days as a function of the significant physical
      variables (R(2)=0.84). The prediction of O(2) uptake by the model depended highly
      on the interaction between MC and W/BA ratio. A MC outside of the traditional 50
      60% (wet basis) range still resulted in a high level of microbial O(2) uptake as
      long as the W/BA ratio was adjusted to maintain a suitable O(2) exchange in the
      sample. The evolution of OUR in the samples was also investigated, uncovering
      strong associations between short and long-term respirometric indices, such as
      peak OUR and cumulative O(2) consumption (p<0.005). Combining peak OUR data with
      cumulative O(2) consumption after 14 days allowed for accurate predictions of
      cumulative O(2) after 28 days of aeration (R(2)=0.96), implying that future
      studies need only run trials up to 14 days to evaluate the overall O(2)
      consumption or biodegradability of similar sludge mixtures.

PMID- 19398321
TI  - Changes in cadmium mobility during composting and after soil application.
AB  - The effect of twelve weeks of composting on the mobility and bioavailability of
      cadmium in six composts containing sewage sludge, wood chips and grass was
      studied, along with the cadmium immobilization capacity of compost. Two different
      soils were used and Cd accumulation measured in above-ground oat biomass (Avena
      sativa L.). Increasing pH appears to be an important cause of the observed
      decreases in available cadmium through the composting process. A pot experiment
      was performed with two different amounts of compost (9.6 and 28.8 g per kg of
      soil) added into Fluvisol with total Cd 0.255 mg kg(-1), and contaminated
      Cambisol with total Cd 6.16 mg kg(-1). Decrease of extractable Cd (0.01 mol l(-1)
      CaCl(2)) was found in both soils after compost application. The higher amount of
      compost immobilized an exchangeable portion of Cd (0.11 mol l(-1) CH(3)COOH
      extractable) in contaminated Cambisol unlike in light Fluvisol. The addition of a
      low amount of compost decreased the content of Cd in associated above-ground oat
      biomass grown in both soils, while a high amount of compost decreased the Cd
      content in oats only in the Cambisol.

PMID- 19398322
TI  - Protein chips and nanomaterials for application in tumor marker immunoassays.
AB  - Recent advances in molecular biology elucidate that tumor markers play an
      important role in diagnosis, prognosis and providing insights into the etiology
      of cancer. Widespread use of tumor markers in healthcare will ultimately depend
      upon the detection of many tumor markers with high selectivity and sensitivity.
      This goal has not been obtained with conventional methods which are time
      consuming, have poor precision, or experience difficulty in realizing automation.
      Recently, much attention has been paid to the use of electrochemical
      immunosensors for the detection of tumor markers due to their high sensitivity,
      easy miniaturization and automation. This brief review focuses on the current
      developments, challenges, and trends of electrochemical immunosensors for tumor
      markers based on protein chips. Whereafter, the recent applications of
      nanomaterials in tumor marker immunoassays are reviewed. We also introduce some
      of our group's research works of novel electrochemical immunosensors for the
      determination of tumor markers.

PMID- 19398324
TI  - Accumulation of regulatory T cells in sentinel lymph nodes is a prognostic
      predictor in patients with node-negative breast cancer.
AB  - It has been revealed that sentinel lymph nodes (SLNs) from patients with node
      negative breast cancer involve RT-PCR detected micrometastases and isolated
      tumour cells. However, the prognostic significance of the pathologically
      undetectable micrometastases is still controversial. In this study, we evaluated
      Foxp3 positive regulatory T cells (Treg) in SLNs as host-side immune marker that
      has the potential to detect these micrometastases. In the analyses of training
      set (n=30), elevated Treg was strongly associated with the pathologically
      undetectable micrometastases. In the analyses of validation set (n=129) in
      patients with node-negative, relapse-free survival in patients with elevated Treg
      was significantly shorter than those with lower Treg (p=0.005). Furthermore, in
      multivariate analyses, elevated Treg was correlated with relapse-free survival
      (p=0.012). Our data indicate that Treg may increase in the microenvironment of
      SLNs along with pathologically undetectable micrometastases and is a prognostic
      predictor in patients with node-negative breast cancer.

PMID- 19398323
TI  - Exploiting structural classifications for function prediction: towards a domain
      grammar for protein function.
AB  - The ability to assign function to proteins has become a major bottleneck for
      comprehensively understanding cellular mechanisms at the molecular level. Here we
      discuss the extent to which structural domain classifications can help in
      deciphering the complex relationship between the functions of proteins and their
      sequences and structures. Structural classifications are particularly helpful in
      understanding the mosaic manner in which new proteins and functions emerge
      through evolution. This is partly because they provide reliable and concrete
      domain definitions and enable the detection of very remote structural
      similarities and homologies. It is also because structural data can illuminate
      more clearly the mechanisms by which a broader functional repertoire can emerge
      during evolution.

PMID- 19398325
TI  - Cost comparison study of two different follow-up protocols after surgery for
      oesophageal cancer.
AB  - BACKGROUND AND AIM: Costs of follow-up strategies in patients after surgery for
      oesophageal cancer have not been evaluated. We therefore randomised 109 patients
      to standard outpatient clinic follow-up by a surgeon (n=55) or home visits by a
      specialist nurse (n=54) and compared costs between these two strategies. METHOD:
      Cost comparisons included comprehensive data on hospital costs, diagnostic
      interventions and extramural care. Detailed information on health care
      consumption was obtained from a case record form at 6 weeks, and 3, 6, 9 and 12
      months after randomisation. RESULTS: Total medical costs were lower for nurse-led
      follow-up (euro 2592 versus euro 3798) than standard follow-up, although this
      difference was not statistically significant (p=0.11). This advantage in the
      nurse-led follow-up group was mainly due to lower costs for follow-up visits
      (euro 234 versus euro 503; p<0.001), and a trend towards lower costs for total
      intramural care (euro 1477 versus euro 2277; p=0.19). CONCLUSION: Nurse-led
      follow-up of patients after oesophageal cancer surgery is likely to be cost
      effective and may even generate cost savings. The results of this study further
      support a specific role of nurses in the medical care of patients with malignant
      diseases.

PMID- 19398326
TI  - Health care costs for treatment of disseminated breast cancer.
AB  - The rapid development of the care makes it important to have relevant cost
      information for cost-effectiveness assessments. The aim of this study is to
      estimate the health care cost of a disseminated breast cancer relapse in Sweden.
      A retrospective cohort study of women with disseminated breast cancer in Sweden
      was done. The individual case records were reviewed and all data concerning
      treatments, hospitalisation, examinations and palliative care were collected. The
      study included 53 patients with a total mean cost of 93,700 euros (95% Confidence
      Interval (CI): 78,500 euros - euro109,600 euros ). Drugs and hospitalisations
      were the largest single cost sources. HER2-positive patients had slightly higher
      mean costs (euro123,300), while triple negative patients had slightly lower mean
      costs (70,600 euros). The current costs for patients with disseminated breast
      cancer are considerably higher than those previously shown, which may have
      important consequences for economic evaluations of interventions aimed at
      reducing the risk of disseminated breast cancer.

PMID- 19398327
TI  - How effective are breast cancer screening programmes by mammography? Review of
      the current evidence.
AB  - Randomised controlled trials showed that breast cancer screening by mammography
      reduces breast cancer mortality in women over age 50 by 25-30%. However, it was
      not clear if this effect would persist outside the controlled trial environment
      or even could be enhanced. We review the current evidence of the impact of long
      standing breast cancer screening programmes (Australia, Canada, Denmark, Finland,
      Iceland, Italy, the Netherlands, Spain, Sweden and the United Kingdom) on breast
      cancer mortality. The decrease observed in women invited to screening ranges from
      16% to 36%. Breast cancer mortality reductions range from 24% to 48% in women
      having attended at least one screen after correcting for selection bias. Although
      evaluation design, time period studied, participation rates achieved differ, the
      trend in mortality reduction is consistent. Adjuvant therapy is estimated to
      contribute about one third to this decrease. We conclude that mammography
      screening programmes implemented for at least 10 years achieve a similar, but not
      greater mortality reduction as the randomised controlled trials. However, it may
      take some more years before the full impact of these mammography screening
      programmes can be assessed.

PMID- 19398328
TI  - The clinical significance and therapeutic implications of extraprostatic
      invasion.
AB  - Invasion of the prostatic margin by cancer establishes a higher risk of disease
      progression and treatment failure depending upon its extent and other clinical
      factors. Pathological stage is the most important single prognostic indicator,
      but determined reliably only in patients having radical prostatectomy. Tumour
      beyond the prostatic margin or its invasion into the seminal vesicle defines the
      local stage category as T3, and when confirmed by pathological examination the
      extent of prostatic margin involvement has prognostic significance. Prediction of
      extraprostatic invasion may influence therapeutic decisions, but can be difficult
      to determine for the individual patient prior to treatment. In some individuals
      having radical prostatectomy, the finding of extraprostatic invasion is
      unsuspected, and fortunately for the majority of these men the treatment remains
      curative. On the other hand, when extraprostatic invasion is suspected prior to
      or at surgery, wide excision may be necessary to achieve negative surgical
      margins, with other factors contributing independently to the likelihood of
      subsequent progression. Radiotherapy is an effective alternative treatment for
      clinical stage T3 and high-risk clinically localized cancer. Recent technological
      advances and use of combination modality treatment with radiation and hormone
      manipulation have improved survival outcomes and reduced side-effects. Radiation
      also has its place as adjuvant treatment following radical prostatectomy in high
      risk disease, or as salvage following PSA recurrence, with ongoing trials
      evaluating potential benefit and toxicity. For clinically localised stage T3
      prostate cancer, treatment with surgery or radiotherapy may be highly effective,
      but multimodality interventions are increasingly being used for primary treatment
      where clinical assessment indicates that there would otherwise be a high risk for
      disease progression and therapeutic failure.

PMID- 19398329
TI  - Does change in accessibility with conversion depend on both the substrate and
      pretreatment technology?
AB  - The accessibility of cellulase and xylanase enzymes to glucan and xylan,
      respectively, and its change with conversion were measured for pure Avicel glucan
      and poplar solids that had been pretreated by ammonia fiber expansion (AFEX),
      ammonia recycled percolation (ARP), dilute acid, and lime. Avicel and pretreated
      solids were digested to various degrees by cellulase together with beta
      glucosidase enzymes and then cleaned of residual protein via a biological method
      using Protease. Glucan accessibility was determined by purified CBHI (Cel7A)
      adsorption at 4 degrees C, and 4 and 24 h hydrolysis yields were determined for
      solids loading containing equal amounts of glucan (1.0% w/v) and lignin (1.0%
      w/v), in two separate sets of experiments. Consistent with our previous study and
      in contrast to some in the literature, little change in glucan accessibility was
      observed with conversion for Avicel, but glucan and xylan accessibility for real
      biomass varied with the type of pretreatment. For example, AFEX pretreated solids
      showed a negligible change in glucan accessibility for conversion up to 90%,
      although xylan accessibility seemed to decline first and then remained constant.
      On the other hand, a substantial decline in glucan and xylan accessibility with
      conversion was observed for lime pretreated poplar solids, as shown by initial
      hydrolysis rates. Yet, an increase in CBHI adsorption with conversion for lime
      pretreated poplar solids suggested the opposite trend, possibly due to increased
      lignin exposure and/or reduced effectiveness of adsorbed enzyme.

PMID- 19398330
TI  - Synthesis and evaluation of 1-(quinoliloxypropyl)-4-aryl piperazines for atypical
      antipsychotic effect.
AB  - A series of 1-(quinoliloxypropyl)-4-aryl-piperazines has been synthesized and the
      target compounds evaluated for atypical antipsychotic activity in apomorphine
      induced mesh climbing and stereotypic behaviour in mice. The 8-hydroxyquinoline
      ether derivative 14 has emerged as an important lead compound showing a potential
      atypical antipsychotic profile. Employing appropriate physicochemical properties,
      the similarity of the compounds was assessed with respect to some atypical
      antipsychotic drugs as clozapine, ketanserine, ziprasidone and risperidone.

PMID- 19398331
TI  - The application of the phosphoramidate ProTide approach confers micromolar
      potency against hepatitis C virus on inactive agent 4'-azidoinosine: kinase
      bypass on a dual base/sugar modified nucleoside.
AB  - Novel phosphoramidate ProTides derived from 4'-azidoinosine have been prepared
      and evaluated in the replicon assay against hepatitis C Virus (HCV). The parent
      nucleoside analogue is inactive in this assay, while the ProTides are active at
      low microM levels in some cases. This is a rare example of an inosine nucleoside
      analogue with potent antiviral activity and further supports the notion of
      ProTides as a drug discovery motif.

PMID- 19398332
TI  - (S)-Camphorsulfonic acid catalyzed highly stereoselective synthesis of
      pseudoglycosides.
AB  - A mild and efficient synthesis of pseudoglycosides has been developed using metal
      free (S)-camphorsulfonic acid. (S)-CSA acts as an excellent catalyst for
      conversion of 2,4,6-tri-O-acetyl-D-glucal to 2,3-unsaturated O-glycosides. A wide
      range of biologically active natural products, alcohols and thiols could be
      coupled with glucal to give the desired pseudoglycosides in good to excellent
      yields with exclusive alpha-stereoselectivity.

PMID- 19398333
TI  - Chloro-oxime derivatives as novel small molecule chaperone amplifiers.
AB  - Chloro-oxime derivatives were investigated as novel small molecule chaperone
      amplifiers. Lead optimization led to the discovery of compounds that displayed
      potent HSF1 activation activity, significant cytoprotection in MG-132 stress, ER
      stress and PolyQ stress cell models (EC(50)<10 microM).

PMID- 19398334
TI  - Design, synthesis and anticancer activities of hybrids of indole and barbituric
      acids--identification of highly promising leads.
AB  - By combining the structural features of indole and barbituric acid, new hybrid
      molecules were designed and synthesized. Evaluations of these molecules over 60
      cell line panel of human cancer cells have identified two molecules with
      significant anticancer activities. Dockings of two active molecules in the active
      sites of COX-2, thymidylate synthase and ribonucleotide reductase indicate their
      strong interactions with these enzymes.

PMID- 19398335
TI  - Immobilization impairs tactile perception and shrinks somatosensory cortical
      maps.
AB  - Use is a major factor driving plasticity of cortical processing and cortical
      maps. As demonstrated of blind Braille readers and musicians, long-lasting and
      exceptional usage of the fingers results in the development of outstanding
      sensorimotor skills and in expansions of the cortical finger representations.
      However, how periods of disuse affect cortical representations and perception in
      humans remains elusive. Here, we report that a few weeks of hand and arm
      immobilization by cast wearing significantly reduced hand use and impaired
      tactile acuity, associated with reduced activation of the respective finger
      representations in the somatosensory cortex (SI), measured by functional magnetic
      resonance imaging. Hemodynamic responses in the SI correlated positively with
      hand-use frequency and negatively with discrimination thresholds, indicating that
      reduced activation was most prominent in subjects with severe perceptual
      impairment. We found, strikingly, compensatory effects on the contralateral,
      healthy hand consisting of improved perceptual performance compared to healthy
      controls. Two to three weeks after cast removal, perceptual and cortical changes
      recovered, whereas tactile acuity on the healthy side remained superior to that
      on the formerly immobilized side. These findings suggest that brief periods of
      reduced use of a limb have overt consequences and thus constitute a significant
      driving force of brain organization equivalent to enhanced use.

PMID- 19398336
TI  - The signaling peptide EPF2 controls asymmetric cell divisions during stomatal
      development.
AB  - Stomata are pores in the plant epidermis that control carbon dioxide uptake and
      water loss. They are major regulators of global carbon and water cycles [1].
      Several signaling components that regulate stomatal development have been
      characterized. These include a putative secretory peptide EPF1, LRR receptor
      components TMM and ER, and a peptidase SDD1 [2-4]. We have identified EPF2, a
      peptide related to EPF1 that is expressed in proliferating cells of the stomatal
      lineage, known as meristemoids, and in guard mother cells, the progenitors of
      stomata. EPF2 expression during leaf development affects stomatal density on the
      mature leaf. In the absence of EPF2, excessive numbers of cells enter the
      stomatal lineage and produce numerous small epidermal cells that express stomatal
      lineage reporter genes, whereas plants overexpressing EPF2 produce virtually no
      stomata. Results from genetic experiments indicate that EPF2 regulates a
      different aspect of stomatal development to EPF1 and are consistent with EPF2
      acting in a pathway to regulate stomatal density that involves ER and TMM, but
      not SDD1. We propose that EPF2 is expressed earlier in leaf development than EPF1
      and is involved in determining the number of cells that enter, and remain in, the
      stomatal lineage.

PMID- 19398337
TI  - A signaling module controlling the stem cell niche in Arabidopsis root meristems.
AB  - The niches of the Arabidopsis shoot and root meristems, the organizing center
      (OC) and the quiescent center (QC), orchestrate the fine balance of stem cell
      maintenance and the provision of differentiating descendants. They express the
      functionally related homeobox genes WUSCHEL (WUS) and WOX5, respectively, that
      promote stem cell fate in adjacent cells. Shoot stem cells signal back to the OC
      by secreting the CLAVATA3 (CLV3) dodecapeptide, which represses WUS expression.
      However, the signals controlling homeostasis of the root stem cell system are not
      identified to date. Here we show that the differentiating descendants of distal
      root stem cells express CLE40, a peptide closely related to CLV3. Reducing CLE40
      levels delays differentiation and allows stem cell proliferation. Conversely,
      increased CLE40 levels drastically alter the expression domain of WOX5 and
      promote stem cell differentiation. We report that the receptor kinase ACR4,
      previously shown to control cell proliferation, is an essential component, and
      also a target, of CLE40 signaling. Our results reveal how, in contrast to the
      shoot system, signals originating from differentiated cells, but not the stem
      cells, determine the size and position of the root niche.

PMID- 19398338
TI  - A novel form of motility in filopodia revealed by imaging myosin-X at the single
      molecule level.
AB  - Although many proteins, receptors, and viruses are transported rearward along
      filopodia by retrograde actin flow, it is less clear how molecules move forward
      in filopodia. Myosin-X (Myo10) is an actin-based motor hypothesized to use its
      motor activity to move forward along actin filaments to the tips of filopodia.
      Here we use a sensitive total internal reflection fluorescence (TIRF) microscopy
      system to directly visualize the movements of GFP-Myo10. This reveals a novel
      form of motility at or near the single-molecule level in living cells wherein
      extremely faint particles of Myo10 move in a rapid and directed fashion toward
      the filopodial tip. These fast forward movements occur at approximately 600 nm/s
      over distances of up to approximately 10 microm and require Myo10 motor activity
      and actin filaments. As expected for imaging at the single-molecule level, the
      faint particles of GFP-Myo10 are diffraction limited, have an intensity range
      similar to single GFP molecules, and exhibit stepwise bleaching. Faint particles
      of GFP-Myo5a can also move toward the filopodial tip, but at a slower
      characteristic velocity of approximately 250 nm/s. Similar movements were not
      detected with GFP-Myo1a, indicating that not all myosins are capable of
      intrafilopodial motility. These data indicate the existence of a novel system of
      long-range transport based on the rapid movement of myosin molecules along
      filopodial actin filaments.

PMID- 19398339
TI  - Adaptive sugar provisioning controls survival of C. elegans embryos in adverse
      environments.
AB  - The ability to adapt to changing environmental conditions is essential to the
      fitness of organisms. In some cases, adaptation of the parent alters the
      offspring's phenotype [1-10]. Such parental effects are adaptive for the
      offspring if the future environment is similar to the current one but can be
      maladaptive otherwise [11]. One mechanism by which adaptation occurs is altered
      provisioning of embryos by the parent [12-16]. Here we show that exposing adult
      Caenorhabditis elegans to hyperosmotic conditions protects their offspring from
      these conditions but causes sensitivity to anoxia exposure. We show that this
      alteration of survival is correlated with changes in the sugar content of adults
      and embryos. In addition, mutations in gene products that alter sugar homeostasis
      also alter the ability of embryos to survive in hyperosmotic and anoxic
      conditions and engage in the adaptive parental effect. Our results indicate that
      there is a physiological trade-off between the presence of glycerol, which
      protects animals from hyperosmotic conditions, and glycogen, which is consumed
      during anoxia. These two metabolites play an essential role in the survival of
      worms in these adverse environments, and the adaptive parental effect we describe
      is mediated by the provisioning of these metabolites to the embryo.

PMID- 19398340
TI  - Differences between body movement adaptation to calf and neck muscle vibratory
      proprioceptive stimulation.
AB  - Adaptation is essential in maintaining stability during balance-challenging
      situations. We studied, in standing subjects with eyes open and closed, adaptive
      responses of the anteroposterior head, shoulder, hip and knee movements;
      gastrocnemius and tibialis anterior EMG activity and anteroposterior body posture
      when proprioceptive information from the neck or calf muscles underwent vibratory
      perturbations. After 30s of quiet stance, vibratory stimuli were applied
      repeatedly for 200s, and adaption to stimulation was analyzed in four successive
      50s periods. Repeated neck and calf vibration significantly increased linear body
      movement variance at all recorded sites (p<0.001, except neck stimulation with
      eyes closed, EC-neck), increased tibialis anterior (p<0.001, except EC-neck) and
      gastrocnemious muscle activity (p<0.001). Most body movement variances and
      tibialis anterior EMG activity decreased significantly over time (most p
      values<0.01 or lower) and overall, the body leaning forward increased from 5.5
      degrees to 6.5 degrees (p<0.01). The characteristics of the responses were
      influenced by vision and site of vibration, e.g., neck vibration affected body
      posture more rapidly than calf vibration. Our findings support the notion that
      proprioceptive perturbations have different effects in terms of nature, degree
      and adaptive response depending on site of vibratory proprioceptive stimulation,
      a factor that needs consideration in clinical investigations and design of
      rehabilitation programs.

PMID- 19398341
TI  - A systematic review of the efficacy of globus pallidus stimulation in the
      treatment of Parkinson's disease.
AB  - The aim of this study was to systematically review the data published on deep
      brain stimulation (DBS) of the globus pallidus internus (GPi) in Parkinson's
      disease (PD), and to determine its efficacy and optimal stimulation parameters.
      Only 22 of 4,648 articles fulfilled the inclusion and exclusion criteria of the
      study. The data were analysed using the Wilcoxon test. For 327 patients who
      underwent GPi-DBS, the preoperative baseline Unified Parkinson's Disease Rating
      Scale (UPDRS) score, off-medication, mean was 52.7 (range 26.5-77.2). The
      postoperative UPDRS score, off-medication/on-stimulation, mean was 33.7 (range
      18.7-46.2). The delta mean (the difference in mean UPDRS score between baseline
      and maximum follow-up) was 19.1 (range -2.2 to 36.5) (p<0.001). When the
      electrical parameters were compared against the delta UPDRS score, the analysis
      showed that only frequency was correlated with motor improvement (R(2)=0.42,
      p<0.05). Thus, GPi-DBS is a highly effective target for neuromodulation in PD.
      However, we found that significant clinical improvement (>50% delta UPDRS score)
      in PD is achieved at an amplitude of between 2.0V and 3.5V, a pulse-width between
      75 micros and 300 micros and a frequency between 100Hz and 190Hz.

PMID- 19398342
TI  - Deep brain stimulation for cluster headache.
AB  - Cluster headache is a severely debilitating disorder that can remain unrelieved
      by current pharmacotherapy. Alongside ablative neurosurgical procedures,
      neuromodulatory treatments of deep brain stimulation (DBS) and occipital nerve
      simulation have emerged in the last few years as effective treatments for
      medically refractory cluster headaches. Pioneers in the field have sought to
      publish guidelines for neurosurgical treatment; however, only small case series
      with limited long-term follow-up have been published. Controversy remains over
      which surgical treatments are best and in which circumstances to intervene. Here
      we review current data on neurosurgical interventions for chronic cluster
      headache focusing upon DBS and occipital nerve stimulation, and discuss the
      indications for and putative mechanisms of DBS including translational insights
      from functional neuroimaging, diffusion weighted tractography,
      magnetoencephalography and invasive neurophysiology.

PMID- 19398343
TI  - 1,3-dialkyl-8-N-substituted benzyloxycarbonylamino-9-deazaxanthines as potent
      adenosine receptor ligands: Design, synthesis, structure-affinity and structure
      selectivity relationships.
AB  - A number of 1,3-dialkyl-9-deazaxanthines (9-dAXs), bearing a variety of N
      substituted benzyloxycarbonylamino substituents at position 8, were prepared and
      evaluated for their binding affinity to the recombinant human adenosine receptors
      (hARs), chiefly to the hA(2B) and hA(2A) AR subtypes. Several ligands endowed
      with excellent binding affinity to the hA(2B) receptors, but low selectivity
      versus hA(2A) and hA(1) were identified. Among these, 1,3-dimethyl-N-3'-thienyl
      carbamate 15 resulted as the most potent ligand at hA(2B) (K(i)=0.8 nM), with a
      low selectivity versus hA(2A) (hA(2A)/hA(2B)=12.6) and hA(1) (hA(1)/hA(2B)=12.5)
      and a higher selectivity versus hA(3) (hA(3)/hA(2B)=454). When tested in
      functional assays in vitro, compound 15 exhibited high antagonist activities and
      efficacies versus both the A(2A) and A(2B) receptor subtypes, with pA(2) values
      close to the corresponding pK(i)s. A comparative analysis of structure-affinity
      and structure-selectivity relationships of the similar analogues 8-N-substituted
      benzyloxycarbonylamino- and 8-N-substituted phenoxyacetamido-9-dAXs suggested
      that their binding modes at the hA(2B) and hA(2A) ARs may strongly differ.
      Computational studies help to clarify this striking difference arising from a
      simple, albeit crucial, structural change, from CH(2)OCON to OCH(2)CON, in the
      para-position of the 8-phenyl ring.

PMID- 19398344
TI  - Synthesis and antirhinovirus activity of new 3-benzyl chromene and chroman
      derivatives.
AB  - A series of 3-benzyl chromenes and chromans were synthesized and tested in vitro
      against human rhinovirus (HRV) 1B and 14, two representative serotypes for
      rhinovirus group B and A, respectively. All the new compounds, with the exception
      of 3-benzyl-2H-chromene (3a), showed a potent activity against HRV serotype 1B
      within micro or submicromolar range (IC(50)s from 0.11 to 6.62 microM). The low
      cytotoxicity of all the derivatives resulted in compounds with high therapeutic
      index (TI). On the contrary, HRV 14 infection was only weakly inhibited by the
      majority of these compounds. The 3-benzylidenechromans 2b and 2c showed the
      highest anti-HRV 1B activity (IC(50) 0.12 and 0.11 microM, respectively) coupled
      with remarkable TI (625.00 and 340.91, respectively). Mechanism of action studies
      on (Z)-3-(4-chlorobenzylidene)chroman (2b) suggest that the new compounds behave
      as capsid binders and interfere with very early stages of HRV 1B replication,
      similarly to related flavanoids.

PMID- 19398345
TI  - Chlorzoxazone esters of some non-steroidal anti-inflammatory (NSAI) carboxylic
      acids as mutual prodrugs: design, synthesis, pharmacological investigations and
      docking studies.
AB  - The discovery of the inducible isoform of cyclooxygenase enzyme (COX-2) spurred
      the search for anti-inflammatory agents devoid of the undesirable effects
      associated with classical NSAIDs. New chlorzoxazone ester prodrugs (6-8) of some
      acidic NSAIDs (1-3) were designed, synthesized and evaluated as mutual prodrugs
      with the aim of improving the therapeutic potency and retard the adverse effects
      of gastrointestinal origin. The structure of the synthesized mutual ester
      prodrugs (6-8) were confirmed by IR, (1)H NMR, mass spectroscopy (MS) and their
      purity was ascertained by TLC and elemental analyses. In vitro chemical stability
      revealed that the synthesized ester prodrugs (6-8) are chemically stable in
      hydrochloric acid buffer pH 1.2 as a non-enzymatic simulated gastric fluid (SGF)
      and in phosphate buffer pH 7.4 as non-enzymatic simulated intestinal fluid (SIF).
      In 80% human plasma, the mutual prodrugs were found to be susceptible to
      enzymatic hydrolysis at relatively faster rate (t(1/2) approximately 37 and 34
      min for prodrugs 6 and 7, respectively). Mutual ester prodrugs (6-8) were
      evaluated for their anti-inflammatory and muscle relaxation activities. Scanning
      electromicrographs of the stomach showed that the ester prodrugs induced very
      little irritancy in the gastric mucosa of rats after oral administration for
      4days. In addition, docking of the mutual ester prodrugs (6-8) into COX-2 active
      site was conducted in order to predict the affinity and orientation of these
      prodrugs at the enzyme active site.

PMID- 19398347
TI  - Performance measurement of the scintillator with optical fiber detector for boron
      neutron capture therapy.
AB  - The thermal neutron flux can be easily measured in real time by using the
      scintillator with optical fiber (SOF) detector. However the irradiation damage
      under high-intensity neutron flux causes deterioration of the SOF detector due to
      radiation damage to the plastic scintillator in which (6)LiF is blended. After
      irradiating the SOF detector for 4 h (thermal neutron fluence is approximately
      2.0 x 10(13)neutrons/cm(2)), the sensitivity of the SOF detector decreased by
      3.0%. After irradiating the SOF detector for 2 months (thermal neutron fluence
      approximately 6.4 x 10(14)neutrons/cm(2)), the sensitivity was reduced to 42% of
      baseline. Supposing that the thermal neutron fluence is 2 x 10(12)neutrons/cm(2)
      on the surface of a patient in a BNCT treatment, the sensitivity of the SOF
      detector is reduced by approximately 0.3%. This report presents investigations on
      the deterioration of the SOF detector in irradiation experiments.

PMID- 19398346
TI  - Biological evaluation of boronated unnatural amino acids as new boron carriers.
AB  - There is a pressing need for new and more efficient boron delivery agents to
      tumor cells for use in boron neutron capture therapy (BNCT). A class of boronated
      unnatural cyclic amino acids has demonstrated a remarkable selectivity toward
      tumors in animal and cell culture models, far superior to currently used agents
      in clinical BNCT. One of these amino acids, 1-amino-3
      boronocyclopentanecarboxylic acid (ABCPC), has shown a tumor to blood ratio of 8
      and a tumor to normal brain ratio of nearly 21 in a melanoma bearing mouse model.
      This work represents further biological characterization of this compound for
      tumor targeting in an EMT6 murine mammary carcinoma mouse model and a T98G human
      glioblastoma cell line. Female BALB/c mice bearing EMT6 tumors were injected with
      the fructose complex form of racemic mixtures of cis and trans isomers of ABCPC
      in identical concentrations. Boron concentrations were measured in the tumor,
      blood, brain, skin, and liver tissues at 1, 3, and 5 h post-injection. These
      observations revealed a remarkable difference in racemic mixtures of cis and
      trans isomers in tumor targeting by boron. This implies that further separation
      of the L and D forms of this compound may enhance tumor targeting to an even
      higher degree than that provided by the racemic mixtures. Since the uptake
      measurements were made in homogenized tumor and normal tissues, little is known
      about the subcellular location of the boron arising from the various isomeric
      forms of the amino acid. To study subcellular delivery of boron from ABCPC in
      T98G human glioblastoma cells, we employed secondary ion mass spectrometry (SIMS)
      based technique of ion microscopy, which is capable of quantitatively imaging
      isotopic (elemental) gradients in cells and tissues at 500 nm spatial resolution.
      The T98G cells were exposed to the nutrient medium containing 100 ppm boron
      equivalent of a mixture of both L and D isomers of ABCPC in the form of a
      fructose complex for 1 h. Following this treatment, the cells were fast frozen,
      freeze-fractured, and freeze-dried for SIMS analysis. Within an hour of exposure,
      ABCPC provided partitioning of intracellular to extracellular boron of 3/1. SIMS
      imaging revealed that boron from ABCPC was distributed throughout the cell,
      including the nucleus. This level of boron delivery within an hour of exposure is
      superior to p-boronophenylalanine (BPA) and sodium borocaptate (BSH), which have
      been previously studied by SIMS in the same cell line. These encouraging
      observations provide compelling support for further isomeric separations of ABCPC
      into the D and L forms for enhanced tumor targeting and continued testing of
      these compounds as new boron carriers in BNCT.

PMID- 19398348
TI  - Survival benefit from boron neutron capture therapy for the newly diagnosed
      glioblastoma patients.
AB  - OBJECTIVE: Since 2002-2007, we applied boron neutron capture therapy (BNCT) to
      >50 cases of malignant gliomas (MGs) with epithermal neutron irradiations.
      Recently, we showed the early radiographical improvement of malignant glioma
      patients by our modified BNCT, with simultaneous use of BPA (borono
      phenylalanine) and BSH (sodium borocaptate). In this time, we focused on the
      survival benefit from BNCT for the newly diagnosed glioblastoma patients.
      METHODS: BNCT group including 21 newly histological confirmed glioblastoma
      patients treated with surgical removal followed by BNCT in Osaka Medical College
      during 2002-2006 period. Ten patients were treated with BNCT only, and in the
      other 11 patients, 20-30 Gy fractionated external beam X-ray irradiation therapy
      (XRT) was performed after BNCT. No chemotherapy was administered until tumor
      progression was observed. RESULTS: Treatments were well tolerated. Any kind of
      acute systemic or local severe toxicity were not demonstrated. Mean over all
      survival of the patients treated by BNCT was 20.7 and the median was 15.6 months
      with 2-years survival of 25%. Stratification by RPA criteria showed 6, 6, 8 and 1
      patients, respectively, in classes III-VI. Three patients out of six in class III
      and one out of eight in class V are alive at the end point of this study. All the
      patients in classes IV and VI died. Median survival time for the BNCT group
      compared to the RTOG database was as follows: 20.6 months vs. 17.9 months for
      class III; 16.9 months vs. 11.1 months for class IV; 13.2 months vs. 8.9 months
      for class V. CONCLUSION: The RTOG RPA prognostic criteria were helpful in
      establishing which class of glioma patients could potentially benefit from BNCT.
      BNCT showed a survival benefit in all of the RPA classes of the RTOG database not
      only for the good prognosis group.

PMID- 19398349
TI  - A diurnally regulated dehydrin from Avicennia marina that shows nucleo
      cytoplasmic localization and is phosphorylated by Casein kinase II in vitro.
AB  - Dehydrins have a key role in protecting plants from dehydration stress. We report
      here the isolation of two cDNAs coding for the same dehydrin, AmDHN1 and AmDHN1a
      from salt stressed leaves of Avicennia marina (Forsk.) Vierh. by EST library
      screening. AmDHN1 was found to contain a retained intron that was absent in
      AmDHN1a. AmDHN1 expression in the context of various environmental stresses was
      investigated. In leaves, AmDHN1 shows a diurnal pattern of regulation and is
      induced only by mannitol application. In roots, AmDHN1 is rapidly induced by
      salinity (NaCl) and dehydration stress (PEG and mannitol). A fragment of 795 bp
      corresponding to the 5' upstream region of AmDHN1 was isolated by TAIL-PCR. In
      silico analysis of this sequence reveals the presence of putative stress
      regulatory elements (ABRE, DRE, MYB and MYC binding sequences). Putative
      phosphorylation sites for Casein kinase II were identified in the AmDHN1a ORF. In
      vitro phosphorylation of Escherichia coli expressed Trx-AmDHN1a by Casein kinase
      II was observed that was reversed by Shrimp Alkaline Phosphatase treatment. A
      putative nuclear targeting domain was identified in the translated AmDHN1a ORF
      and stably transformed AmDHNIa-GFP was found to show nucleo-cytoplasmic
      localization in tobacco guard cells. As observed for maize Rab 17, the
      phosphorylation of AmDHN1a may contribute to its nuclear localization.

PMID- 19398350
TI  - Non-invasive assessment of muscle fiber conduction velocity during an incremental
      maximal cycling test.
AB  - Muscle fiber conduction velocity (MFCV) gives critical information on
      neuromuscular control and can be considered a size principle parameter, being
      suggestive of motor unit recruitment strategies. MFCV has been recently measured
      during constant-load sub-maximal cycling exercise and was found to correlate
      positively with percentage of type I myosin heavy chain. The aim of this study
      was to test the hypothesis that MFCV measured during an incremental cycling test
      using surface electromyography (sEMG), can be sensitive to the different
      metabolic requests elicited by the exercise. In particular, the relationship
      between ventilatory threshold (T-vent), V(')O(2max) and MFCV was explored. Eleven
      male physically active subjects (age 30+/-9 years) undertook a 1-min incremental
      cycling test to exhaustion. T-vent and V(')O(2max) were measured using an open
      circuit breath by breath gas analyzer. The sEMG was recorded from the vastus
      lateralis muscle with an adhesive 4-electrodes array, and the MFCV was computed
      on each sEMG burst over the last 30-s of each step. The mean V(')O(2max) obtained
      during the maximal test was 53.32+/-2.33 ml kg(-1) min(-1), and the T-vent was
      reached at 80.77+/-3.49% of V(')O(2max). In all subjects reliable measures of
      MFCV were obtained at every exercise intensity (cross correlation values >0.8).
      MFCV increased linearly with the mechanical load, reaching a maximum value of
      4.28+/-0.67 ms(-1) at an intensity corresponding to the T-vent. Thereafter, MFCV
      declined until maximal work intensities. This study demonstrates that MFCV can be
      used as non-invasive tool to infer MUs recruitment/derecruitment strategies even
      during dynamic exercise from low to maximal intensities.

PMID- 19398351
TI  - Endovascular stent-graft management of aortic intramural hematomas.
AB  - PURPOSE: To report initial experience with endovascular stent-grafting in aortic
      intramural hematoma (IMH). MATERIALS AND METHODS: From 2000 to 2006, 15 patients
      (mean age, 67 years; range, 54-83 y) underwent endovascular treatment of aortic
      IMH. Thirteen patients were admitted for acute aortic syndrome and two for
      traumatic aortic injury. An endovascular procedure was performed as primary
      treatment for four patients (type A IMH, n = 3; type B IMH, n = 1) and as a
      second-line therapy in 11 patients because of unfavorable evolution (type A IMH,
      n = 1; type B IMH, n = 10). All stent-grafts were placed in the descending aorta,
      even for type A IMH. The mean follow-up was 21 months (range, 6-72 months).
      RESULTS: The primary success rate was 93%, with complete exclusion of the lesion
      (n = 14). Exclusion was partial for one patient with a type I endoleak (7%). The
      30-day mortality rate was zero. IMH evolution was favorable in all cases, with
      decreased aortic wall thickening (n = 8) or complete regression (n = 7).
      Complications associated with endovascular repair were mainly related to aneurysm
      formation (20%). The late death rate was 7%. CONCLUSIONS: Endovascular stent
      graft treatment can be performed in the management of complicated IMH, even in
      some cases of type A IMH, when an intimal lesion is located in the isthmus or
      descending aorta with contraindications to surgery. This procedure offers low
      morbidity and mortality rates, representing a feasible therapeutic option
      especially for elderly patients with comorbidities. Further studies are necessary
      to confirm these preliminary results.

PMID- 19398352
TI  - An emergency visceral hybrid procedure for ruptured thoraco-abdominal aortic
      aneurysms.
AB  - Rupture of a thoraco-abdominal aortic aneurysm (TAAA) is usually lethal. Patients
      with contained ruptures, who reach the hospital, have traditionally been
      subjected to open reconstructive surgery. However, especially in older patients,
      open surgery has a high mortality and morbidity rate. Visceral hybrid procedures
      (VHPs) can provide an alternative in this high-risk patient group. We present a
      literature review of VHPs with a focus on acute TAAAs.

PMID- 19398353
TI  - The circadian rhythm and its interaction with human epilepsy: a review of
      literature.
AB  - Knowledge on the interaction between circadian rhythm and human epilepsy is
      relatively poor, although if it exists, this interaction may be of value for
      better knowledge of pathophysiology and for timing of diagnostic procedures and
      therapy. It appears that human seizure occurrence may have 24-h rhythmicity,
      depending on the origin. These findings are endorsed by animal studies. Rats
      placed in constant darkness showed spontaneous limbic seizures occurring in an
      endogenously mediated circadian pattern. More studies are available on the
      influence of epilepsy on circadian rhythms. Significant differences in
      chronotypes between patients with different epilepsy syndromes have been found
      and numerous studies have described influences of epilepsy and seizures on sleep.
      In contrast, knowledge on (core) body temperature and clock genes in patients is
      minimal. Reduced heart rate variability and changed hormone levels, which are
      under the influence of the biological clock, have been observed in people with
      epilepsy. In short, large gaps in the knowledge about the interaction of
      circadian rhythm and human epilepsy still remain. Proposals for studies in this
      borderline area between the biological clock and epilepsy will be discussed.

PMID- 19398354
TI  - Sleep problems in autism spectrum disorders: prevalence, nature, & possible
      biopsychosocial aetiologies.
AB  - As considerably more people are diagnosed with an autism spectrum disorder (ASD),
      interest in the associated behaviours, including sleep problems has increased.
      This has resulted in a subsequent increase in the research related to the sleep
      problems occurring in people with an ASD. This article summarizes and evaluates
      the current literature related to a) the higher prevalence of a sleep problem
      compared to typically developing children, b) the specific types of sleep
      problems for people with an ASD, and c) the possible aetiology of sleep problems
      in the ASDs within a biopsychosocial framework. It is concluded that recent
      studies confirm that the majority of this population are likely to experience
      sleep difficulties, with settling issues in children with an ASD the most
      commonly reported. However, exploration of the types of sleep difficulties and
      associated aetiological factors in the ASDs is still in its infancy.

PMID- 19398355
TI  - Assessing equine prospective memory in a Y-maze apparatus.
AB  - Eight horses were tested in a Y-maze to see if they would approach the side on
      which they had seen and heard food being delivered into a food trough. The horses
      were tested in five experimental contexts: immediate release (IR), delayed
      release 3s (3DR), 6s (6DR), 9s (9DR) and 12s (12DR) after food delivery.
      Individual subjects performed five IR trials, followed by five each of 3DR, 6DR,
      9DR and 12DR trials. A re-rest was performed 1 week later. Data were analysed by
      log-linear analysis of frequencies. The results showed that the horses were
      capable of achieving the correct choice during IR trials, were successful during
      the DR trials and improved marginally during the re-test. The findings suggest
      that horses could have a trainable form of prospective memory and benefit from
      incremental memory-training exercises. However, there is a risk of overestimating
      equine cognitive ability and unnecessary reinforcement delays are likely to lead
      to welfare and training setbacks within equitation.

PMID- 19398356
TI  - Pressure on the horse's withers with three styles of blanket.
AB  - The objective of this study was to compare total force and localised pressure on
      horses' withers with three blanket styles (straight cut, V-shaped insert, cutback
      withers). Three pressure recordings, each of 5s duration, were taken in order to
      determine blanket pressure on the withers during standing and walking in 12
      horses. Means+/-SD were calculated for the following variables and compared
      across blankets: total force, mean pressure, maximal pressure, and area with
      pressure >4 kPa. For standing trials, the blanket with the V-shaped insert had
      the lowest total force and smallest area with pressure >4 kPa (P<0.05). For
      walking trials, the straight cut blanket had the highest total force, maximal
      pressure, mean pressure, and largest area with pressure >4 kPa (P<0.05). The
      results indicate that blanket style affects force and pressure on the horse's
      withers and that blankets may exert sufficient pressure on the withers to induce
      the formation of pressure sores.

PMID- 19398357
TI  - Detection of Francisella piscicida in Atlantic cod (Gadus morhua L) by the loop
      mediated isothermal amplification (LAMP) reaction.
AB  - The loop-mediated isothermal amplification (LAMP) reaction was evaluated for its
      speed and sensitivity in detecting the presence of Francisella piscicida, the
      causative agent of francisellosis in Atlantic cod (Gadus morhua). Four primer
      sets, consisting of two outer and two inner, were designed from the groEL gene of
      the pathogen. The LAMP reaction was optimised at 63 degrees C for 1h using
      bacterial genomic DNA as the template and the products were visualised under
      ultra-violet light and analysed by agarose gel electrophoresis. A ladder-like
      pattern of bands, specific for F. piscicida, was amplified from positive samples.
      The method was highly specific for the detection of F. piscicida and was 100
      times more sensitive than conventional PCR. In addition, the LAMP assay was able
      to detect the pathogen in kidney and splenic samples of naturally-infected
      Atlantic cod.

PMID- 19398358
TI  - Improvements to selective refocusing phased (SERFph) experiments.
AB  - Selective refocusing experiments are very powerful for extracting proton-proton
      couplings one by one. However we demonstrate in the present work that various
      spectral artefacts are produced by the initial sequence and we show that the
      combined addition of a refocusing pi pulse and a zero-quantum filter greatly
      improves the experimental sensitivity, and moreover leads to observation of pure
      absorption lineshapes in the resulting phased 2D spectrum. These developments are
      applied to the differentiation of enantiomers dissolved in a chiral liquid
      crystal.

PMID- 19398359
TI  - RF pulses for in vivo spectroscopy at high field designed under conditions of
      limited power using optimal control.
AB  - Localized in vivo spectroscopy at high magnetic field strength (>3T) is
      susceptible to localization artifacts such as the chemical shift artifact and the
      spatial interference artifact for J-coupled spins. This latter artifact results
      in regions of anomalous phase for J-coupled spins. These artifacts are
      exacerbated at high magnetic field due to the increased frequency dispersion,
      coupled with the limited RF pulse bandwidths used for localization. Approaches to
      minimize these artifacts include increasing the bandwidth of the frequency
      selective excitation pulses, and the use of frequency selective saturation pulses
      to suppress the signals in the regions with anomalous phase. The goal of this
      article is to demonstrate the efficacy of optimal control methods to provide
      broader bandwidth frequency selective pulses for in vivo spectroscopy in the
      presence of limited RF power. It is demonstrated by examples that the use of
      optimal control methods enable the generation of (i) improved bandwidth selective
      excitation pulses, (ii) more efficient selective inversion pulses to be used for
      generation of spin echoes, and (iii) improved frequency selective saturation
      pulses. While optimal control also allows for the generation of frequency
      selective spin echo pulses, it is argued that it is more efficient to use dual
      inversion pulses for broadband generation of spin echoes. Finally, the optimal
      control routines and example RF pulses are made available for downloading.

PMID- 19398360
TI  - A case of brucellosis with abscess of the iliacus muscle, olecranon bursitis, and
      sacroiliitis.
AB  - Brucellosis is a systemic infection involving many organs and tissues. The
      musculoskeletal system is one of the most commonly affected. The disease can
      present with sacroiliitis, peripheral arthritis, spondylitis, paraspinal abscess,
      bursitis, and osteomyelitis. A 25-year-old male patient was admitted with fever
      of 20-day duration, right-sided hip pain, and night sweating. A Brucella standard
      tube agglutination test was positive at a titer of 1/160. Magnetic resonance
      imaging (MRI) of the hip joint showed right sacroiliitis and a hyperintense,
      nodular, lobulated mass within the right iliacus muscle, consistent with abscess.
      The patient was started on intramuscular streptomycin at a dose of 1 g/day, oral
      rifampin 600 mg/day, and doxycycline 200 mg/day. On day 20 of treatment, the
      patient was admitted with swelling and pain over the left elbow for the past
      week. MRI of the left elbow was performed, which showed fluid edema suggestive of
      olecranon bursitis. Taking the patient's complaints into consideration, rifampin
      and doxycycline treatment were maintained for a year. Pain at the hip joint and
      elbow resolved and MRI findings disappeared. Abscess of the iliacus muscle, which
      has not been reported before, and the olecranon bursitis that developed during
      treatment make this case worth presenting.

PMID- 19398362
TI  - Thrombosis associated with varicella zoster in an adult.
AB  - The incidence of varicella zoster in adults is increasing, and may be associated
      with a number of significant complications. An adult male presented with
      varicella zoster complicated by pneumonitis and thrombosis, leading to a below
      knee amputation. Thrombosis with varicella zoster has been associated with
      vasculitis and free protein S deficiency. Other microthrombotic complications,
      such as purpura fulminans, are more common in children. Current treatment
      recommendations include acetaminophen (paracetamol) and lotions for symptomatic
      treatment. Intravenous acyclovir is recommended in the treatment of complicated
      varicella zoster, although it has not been shown to reduce the incidence of
      complications.

PMID- 19398361
TI  - A multi-level analysis of risk factors for Schistosoma japonicum infection in
      China.
AB  - OBJECTIVE: The aim of this study was to explore the risk factors of
      schistosomiasis japonica in China, using a hierarchical multi-level model with
      individuals nested within villages. METHODS: A cross-sectional survey of
      schistosomiasis japonica was conducted in 16 villages in the Chinese province of
      Hunan. A multi-level modeling technique (HLM version 6.04) was used to assess
      risk factors of schistosomiasis. The results from this multi-level model were
      compared with those from a conventional single-level logistic regression model.
      RESULTS: A total of 10,245 individuals were enrolled in this study, of whom about
      4.1% were infected with Schistosoma japonicum. In the multi-level model analysis,
      individual level variables such as gender, age, and occupation, and village level
      variables such as type of S. japonicum endemic area, drinking water source,
      sewage treatment, June temperature, and April rainfall were associated with
      schistosomiasis japonica infection. Conventional single-level logistic regression
      analysis selected more independent variables, and had narrower confidence
      intervals around the corresponding regression coefficients. In particular, per
      capita income, precipitation in October, and density of infected snails were
      statistically significant in the conventional single-level logistic regression
      analysis but not in the multi-level model. CONCLUSIONS: Multi-level modeling is a
      useful tool in the analysis of risk factors of schistosomiasis japonica. Because
      the multi-level model captures the hierarchical structure of the data, it may be
      considered a more appropriate analytical tool for data of this type. This
      technique may also be useful in the analysis of other infectious diseases with a
      similar hierarchical structure.

PMID- 19398363
TI  - [Robotic assistance in gynaecological surgery: State-of-the-art].
AB  - From the Automated Endoscopic System for Optimal Positioning (AESOP), a robotic
      arm which operates the laparoscope, to the robots Zeus and da Vinci, robotic
      assistance in gynaecological endoscopic surgery has continuously evolved for the
      last fifteen years or so. It has brought about new technical advancements: the
      last generation robots offer a steady three-dimensional image, improved
      instrument dexterity and precision, higher ergonomics and comfort for the
      surgeon. The da Vinci robotic system has been used without evincing any specific
      morbidity in various cases, notably for tubal reanastomosis, myomectomy,
      hysterectomy, pelvic and para-aortic lymphadenectomy or sacrocolpopexy amongst
      others. Robotic assistance in gynaecology is thus feasible. Like conventional
      laparoscopic surgery, it allows decreased blood loss and morbidity as well as
      shorter hospital stay, as compared to laparotomy. It might indeed allow many
      surgical teams to perform minimally invasive surgical procedures which they were
      not used to performing by laparoscopy. Randomized prospective studies are needed
      to define its indications more precisely. Besides, its medico-financial impact
      should be evaluated too.

PMID- 19398364
TI  - [Use of enfurvitide in pregnancy in HIV positive women in seven cases].
AB  - OBJECTIVE: With a panel of more than 22 drugs, the treatment of HIV subjects is
      nowadays quite easier. But due to the number of multiparus women often harbouring
      a multidrug resistant virus, or seen late in pregnancy or inobservant, taking
      care of these pregnancies remains difficult. The use of enfuvirtide seems quite
      interesting for these situations. PATIENTS AND METHODS: In a retrospective study,
      we have focused our work on the consequences of enfuvirtide used in seven
      pregnancies, paying particular attention to efficacy, pharmacokinetics and
      tolerance. RESULTS: The use of enfuvirtide during 30 days in average seems safe
      and the tolerance was satisfactory in all seven cases. All infants are
      seronegative without abnormalities. The dosages in umbilical cord were negative.
      Five women experienced an elective caesarean, one had caesarean section in
      emergency, and one had a vaginal delivery. DISCUSSION AND CONCLUSION: The 23
      cases published in the English literature indicate the interest of enfuvirtide
      use in these difficult situations. Indeed, enfuvirtide is injectable, favouring
      the adherence; it has a good tolerance, a quick efficacy and no placental
      transfer. Evidently, enfuvirtide is always prescribed in association.

PMID- 19398365
TI  - Extreme violence--homicide; an analysis of 265 cases from the offices of JMO
      Colombo and Ragama--a study from Sri Lanka.
AB  - Violence in a society can be categorized into many areas such as interpersonal
      violence, domestic violence, violence against children, violence of human rights,
      violence due to wars etc. The most extreme form of violence is killing of another
      human. To study whether the underlying reasons (motives) for killing has a
      relationship to the methods employed for killing. A retrospective descriptive
      study based on autopsy reports, magistrate orders and case notes attached was
      carried out on all the cases examined at the office of the JMO Colombo and Ragama
      from July 2005 to June 2006. The data were analyzed using SPSS statistical
      package. Out of 265 autopsy examinations alleged to be homicides, 39% of deaths
      were related to terrorist acts while previous enmity was recorded in 35% of
      cases. The commonest method of homicide was firearms (31%) while explosives
      recorded the second highest (28%). Blunt force and sharp force trauma were the
      reasons for 23% and 14% of homicides respectively. Almost all the deaths related
      to war was caused by firearms and bombs (96%) where as 47% of previous enmity
      deaths were caused by firearms. Firearms were never used in homicides of sudden
      provocation or drunken brawls. The increased use of firearms was not only seen in
      terrorism related homicides, but also in homicides related to previous enmity.
      Further research is needed in this area as to why it occurs despite having a
      tight firearm policy in Sri Lanka.

PMID- 19398366
TI  - Characterization of pediatric wheelchair kinematics and wheelchair tiedown and
      occupant restraint system loading during rear impact.
AB  - This study characterizes pediatric wheelchair kinematic responses and wheelchair
      tiedown and occupant restraint system (WTORS) loading during rear impact. It also
      examines the kinematic and loading effects of wheelchair headrest inclusion in
      rear impact. In two separate rear-impact test scenarios, identical WC19-compliant
      manual pediatric wheelchairs were tested using a seated Hybrid III 6-year-old
      anthropomorphic test device (ATD) to evaluate wheelchair kinematics and WTORS
      loading. Three wheelchairs included no headrests, and three were equipped with
      slightly modified wheelchair-mounted headrests. Surrogate WTORS properly secured
      the wheelchairs; three-point occupant restraints properly restrained the ATD. All
      tests used a 26km/h, 11g rear-impact test pulse. Headrest presence affected
      wheelchair kinematics and WTORS loading; headrest-equipped wheelchairs had
      greater mean seatback deflections, mean peak front and rear tiedown loads and
      decreased mean lap belt loads. Rear-impact tiedown loads differed from previously
      measured loads in frontal impact, with comparable tiedown load levels reversed in
      frontal and rear impacts. The front tiedowns in rear impact had the highest mean
      peak loads despite lower rear-impact severity. These outcomes have implications
      for wheelchair and tiedown design, highlighting the need for all four tiedowns to
      have an equally robust design, and have implications in the development of rear
      impact wheelchair transportation safety standards.

PMID- 19398367
TI  - Techniques.

PMID- 19398368
TI  - A study of conformational stability and vibrational assignments of 1
      aminocyclopropanecarboxylic acid c-C3H4(NH2)-COOH.
AB  - The structural stability of 1-aminocyclopropanecarboxylic acid was investigated
      at DFT-BLYP, DFT-B3LYP and ab initio MP2 levels of theory with 6-311G(**) basis
      set. The molecule was predicted at the three levels of calculation to exist in
      cis-syn<-->trans-syn conformational equilibrium. The equilibrium constants for
      the conformational interconversion were calculated and found to correspond to an
      equilibrium mixture of about 35% cis-syn and 65% trans-syn conformations at
      298.15 K. The cis-trans rotational barrier and the NH(2)syn-anti inversion
      barrier were estimated to be about 6 and 7 kcal/mol, respectively. The O-H
      rotational barrier was calculated to be of the order 12-14 kcal/mol. The
      vibrational frequencies of the two stable conformers of the acid were computed at
      the BLYP and the B3LYP levels of theory. Only vibrational assignments were
      provided for the low energy trans-syn conformer on the basis of normal coordinate
      analysis and experimental data. No clear evidence was found for the presence of
      the second high energy cis-syn structure in the spectra of the molecule.

PMID- 19398369
TI  - A ratiometric fluorescent sensor for zinc ions based on covalently immobilized
      derivative of benzoxazole.
AB  - In the present paper, we describe the fabrication and analytical characteristics
      of fluorescence-based zinc ion-sensing glass slides. To construct the sensor, a
      benzoxazole derivative 4-benzoxazol-2'-yl-3-hydroxyphenyl allyl ether (1) with a
      terminal double bond was synthesized and copolymerized with 2-hydroxyethyl
      methacrylate (HEMA) on the activated surface of glass slides by UV irradiation.
      In the absence of Zn(2+) at pH 7.24, the resulting optical sensor emitted
      fluorescence at 450 nm via excited-state intramolecular proton transfer (ESIPT).
      Upon binding with Zn(2+), the ESIPT process was inhibited resulting in a 46 nm
      blue-shift of fluorescence emission. Thus, the proposed sensor can behave as a
      ratiometric fluorescent sensor for the selective detection of Zn(2+). In
      addition, the sensor shows nice selectivity, good reproducibility and fast
      response time. Cd(2+) did not interfere with Zn(2+) sensing. The sensing membrane
      demonstrates a good stability with a lifetime of at least 3 months. The linear
      response range covers a concentration range of Zn(2+) from 8.0x10(-5) to 4.0x10(
      3) mol/L and the detection limit is 4.0x10(-5) mol/L. The determination of Zn(2+)
      in both tap and river water samples shows satisfactory results.

PMID- 19398370
TI  - Learning ontological rules to extract multiple relations of genic interactions
      from text.
AB  - INTRODUCTION: Information extraction (IE) systems have been proposed in recent
      years to extract genic interactions from bibliographical resources. They are
      limited to single interaction relations, and have to face a trade-off between
      recall and precision, by focusing either on specific interactions (for
      precision), or general and unspecified interactions of biological entities (for
      recall). Yet, biologists need to process more complex data from literature, in
      order to study biological pathways. An ontology is an adequate formal
      representation to model this sophisticated knowledge. However, the tight
      integration of IE systems and ontologies is still a current research issue, a
      fortiori with complex ones that go beyond hierarchies. METHOD: We propose a rich
      modeling of genic interactions with an ontology, and show how it can be used
      within an IE system. The ontology is seen as a language specifying a normalized
      representation of text. First, IE is performed by extracting instances from
      natural language processing (NLP) modules. Then, deductive inferences on the
      ontology language are completed, and new instances are derived from previously
      extracted ones. Inference rules are learnt with an inductive logic programming
      (ILP) algorithm, using the ontology as the hypothesis language, and its
      instantiation on an annotated corpus as the example language. Learning is set in
      a multi-class setting to deal with the multiple ontological relations. RESULTS:
      We validated our approach on an annotated corpus of gene transcription
      regulations in the Bacillus subtilis bacterium. We reach a global recall of 89.3%
      and a precision of 89.6%, with high scores for the ten semantic relations defined
      in the ontology.

PMID- 19398371
TI  - Delta-alpha ratio correlates with level of recovery after neurorehabilitation in
      patients with acquired brain injury.
AB  - OBJECTIVE: To explore the relationship between three QEEG global indexes and
      their association with functional outcome after neurorehabilitation in non-acute
      acquired brain injury (ABI) patients (traumatic brain injury and stroke).
      METHODS: Twenty-one adult ABI patients in post-acute phase were studied. Delta
      alpha ratio (DAR), Power Ratio Index (PRI) and Mean Brain Symmetry Index (mBSI)
      were calculated from resting-state EEG taken at admission. These indexes and
      other clinical variables were correlated with functional recovery achieved after
      six months of neurorehabilitation. RESULTS: DAR showed the highest strength of
      association with the functional outcome measure (rho=-0.65, P=0.002). The other
      QEEG indexes and clinical variables showed modest non-significant correlations. A
      posteriori group analysis showed higher DAR in patients with poor recovery as
      compared to good recovery patients. CONCLUSIONS: Functional recovery after
      neurorehabilitation appears to be associated with a number of clinical and
      neurophysiological variables. Among the latter, the ratio between delta and alpha
      may play a significant role in predicting and monitoring functional
      rehabilitation outcome. SIGNIFICANCE: Neurophysiological assessment of ABI
      patients may be an important tool in monitoring and predicting outcomes after
      neurorehabilitation.

PMID- 19398372
TI  - The influence of air pollution during intrauterine development and early
      childhood on respiratory functions at later age.
AB  - AIM: The aim of this study is to estimate the influence of high levels of air
      pollution during intrauterine development and early childhood on the respiratory
      functions at a later stage in life. MATERIAL AND METHODS: The subjects were
      children from Dimitrovgrad - one of the most industrialized areas in Bulgaria.
      The transition to market economy (after 1989) was accompanied by a great drop in
      industrial production and levels of air pollutants respectively. A complete
      functional respiratory test of 122 clinically healthy ten-year-old children (48
      boys and 74 girls) from Dimitrovgrad was carried out (MasterScreen Diffusion,
      Jaeger, Wuerzburg, Germany). The participants were distributed in 3 groups: First
      group (I), n=60 - born and lived to their fifth year of age under conditions of
      heavy air pollution, and whose mothers had their pregnancies in the same
      environment; Second group (II), n=39 - born and lived after the abrupt production
      drop, under considerably lower level of pollution, but whose mothers had their
      pregnancies prior to that; Third group (III), n=23 - born after the abrupt
      production drop, lived in conditions of considerably lower level of pollution,
      and whose mothers had their pregnancies in this more favorable environment.
      RESULTS: The lowest functional indicators of external breathing in the children
      from the first group were found. FEV(1%pred) - 100.41+/-12.05 (I), 107.38+/-12.55
      (II), 111.56+/-11.08 (III), P(IvsII)=0.017, P(IvsIII)=0.001, P(IIvsIII)=0.57;
      TLC(%pred) - 89.85+/-8.54 (I), 102.76+/-11.57 (II), 102.83+/-11.47 (III),
      P(IvsII)<0.0001, P(IvsIII)<0.0001, P(IIvsIII)=1. CONCLUSION: The research makes
      an attempt to provide evidence for the negative influence of high levels of air
      pollution during the intrauterine development and during early childhood,
      manifested by respiratory limitations at a later stage of childhood. It is known
      that the influence of air pollution with TSPM and SO(2) during the first 5 years
      of life is more important than that in intrauterine development for the
      respiratory functions. Data is lacking with concern to intrauterine programing of
      respiratory function. Further research is necessary for a detailed elucidation of
      the problem.

PMID- 19398373
TI  - Reticulated platelet monitoring after autologous peripheral haematopoietic
      progenitor cell transplantation.
AB  - Reticulated platelets are the youngest marker of megakaryopoiesis. We monitored
      13 haematological patients undergoing autologous peripheral haematopoietic
      progenitor cell transplantation. We used a flow cytometric method based on
      thiazole orange platelet staining. Patients showed a fall in reticulated platelet
      percentage at a mean of 5 days before a nadir of the platelet count. In all
      cases, platelet recovery is preceded by a rise of reticulated platelets; in 10
      cases patients received platelet prophylactic transfusions after RP rise. The
      rise in reticulated platelets is an early sign of engraftment and may represent
      an easy parameter for transfusion management of transplanted patients.

PMID- 19398374
TI  - A longitudinal study of quality of life in patients with chronic heart failure
      following an exercise training program.
AB  - BACKGROUND: Chronic heart failure (CHF) will become one of the greatest medical
      challenges during the next decades. This is especially true with regard to
      elderly patients. Besides medical diagnostics and drug therapy, efficient
      treatment of CHF must also include exercise training. AIMS: The purpose of our
      study was 1) to record health-related quality of life (QOL) in elderly patients
      with CHF and 2) to assess the efficacy of a training program, as well as to
      evaluate any changes detected during a six month follow-up. METHODS: In our non
      randomized study, 116 patients, divided according to age into Group 1 (>70 years)
      and Group 2 (<70 years), took part in a 4-week training program. RESULTS: There
      were differences in the clinical parameters and the QOL between the older and the
      younger patients both after 4 weeks and at the follow-up. After six months,
      however, the older patients again recorded having an inferior QOL to that of the
      younger patients. CONCLUSION: Elderly patients can also benefit from physical
      exercise training, with improvement in clinical parameters and QOL. In order to
      maintain the subjectively improved QOL in the long term, however, continued
      special heart failure education and support is required.

PMID- 19398375
TI  - Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have
      normal invariant natural killer T-cell populations.
AB  - Human invariant natural killer T cells (iNKT cells) are a unique population of T
      cells that express an invariantly rearranged T-cell receptor (TCR) composed of
      TCRValpha24 and TCRVbeta11 chains which recognize glycosphingolipid antigens
      presented by the CD1d molecule. iNKT cells are absent in patients with X-linked
      lymphoproliferative disease (XLP) due to SH2D1A mutation, and are reported to be
      decreased in patients with XLP due to BIRC4 mutations. However, mice deficient in
      the BIRC4 gene product, X-linked Inhibitor of Apoptosis (XIAP), have normal iNKT
      cell populations. Because of this, we studied iNKT cell populations in 6 patients
      with XLP due to BIRC4 mutations, with comparison to 103 pediatric and adult
      normal control samples. We found that iNKT cells constitute 0.008%-1.176% of
      normal peripheral blood T cells, and that iNKT cell populations were normal or
      increased in patients with BIRC4 mutations. We conclude that XLP due to BIRC4
      mutation is not associated with decreased populations of iNKT cells, and that
      XIAP is likely not a requirement for iNKT cell development.

PMID- 19398376
TI  - Monitoring immunosuppression with measures of NFAT decreases cancer incidence.
AB  - Long-term immunosuppression causes a significantly increased risk for the
      development of malignancies in transplanted patients. A link between
      immunosuppression and incidence of cancer is well documented and involves the
      effect of immunosuppression on anti-tumor surveillance and antiviral adaptive
      immune responses. We present a 67-year-old patient with a history of recurrent
      non-melanoma skin cancer. After adjustment of immunosuppressive therapy under
      close pharmacodynamic control, the development of new malignant lesions could be
      prevented. The availability of a quantitative, quick laboratory test for an
      assessment of the individual functional activity of immunocompetent cells that
      are crucial for transplant rejection, defense against viral infection, and tumor
      surveillance along with the ability to adjust doses of immunosuppressive agents
      such that patients are largely protected against malignant disease and/or viral
      infection are important. NFAT-regulated gene expression measured in peripheral
      blood allowed us to predict "safe" immunosuppression. Thus patients could
      maintain a stable allograft function. This represents a breakthrough in
      transplantation medicine and advances our attempts to individualize treatment in
      transplanted patients.

PMID- 19398377
TI  - Changes in gray matter density in fibromyalgia: correlation with dopamine
      metabolism.
AB  - Fibromyalgia (FM) has been associated with alterations in brain morphometry and
      abnormal dopaminergic neurotransmission. Evidence from preclinical models has
      demonstrated that dopamine plays a role in promoting neuronal integrity. We
      therefore sought to confirm previous findings of reduced gray matter density in
      subjects with FM and to determine whether variations in dopamine metabolism might
      affect gray matter density. Voxel-based morphometry was used to evaluate
      anatomical magnetic resonance imaging data from 30 female FM subjects in
      comparison with 20 age- and gender-matched healthy control subjects. In addition,
      data from a subset of subjects from both groups who had previously participated
      in our positron emission tomography study using radiolabeled DOPA (n = 14; 6 FM
      subjects and 8 control subjects) was used to determine whether correlation might
      exist between gray matter density and dopamine metabolism. We found a significant
      reduction in gray matter density within the bilateral parahippocampal gyri, right
      posterior cingulate cortex, and left anterior cingulate cortex. In addition, a
      positive correlation was demonstrated between an index of dopamine metabolism
      from the ventral tegmental area wherein cell bodies of corticolimbic projection
      neurons originate and gray matter density, specifically in the bilateral
      parahippocampal gyri and left pregenual cortex. The current results confirm our
      previous findings that FM is associated with altered brain morphometry.
      Alterations in dopamine metabolism might contribute to the associated changes in
      gray matter density. PERSPECTIVE: Fibromyalgia is associated with reductions in
      gray matter density within brain regions ostensibly involved in phenomena related
      to the disorder, including enhanced pain perception, cognitive dysfunction, and
      abnormal stress reactivity. Given mounting evidence of abnormal dopaminergic
      neurotransmission associated with the disorder, the strong correlation between
      dopamine metabolism and gray matter density provides insight as to the
      pathophysiology that might contribute to these changes.

PMID- 19398378
TI  - An investigation of the hypoalgesic effects of TENS delivered by a glove
      electrode.
AB  - This randomized, placebo-controlled, blinded study investigated the hypoalgesic
      effects of high-frequency transcutaneous electrical nerve stimulation (TENS)
      delivered via a glove electrode compared with standard self-adhesive electrodes.
      Fifty-six TENS-naive, healthy individuals (18 to 50 years old; 28 men, 28 women)
      were randomly allocated to 1 of 4 groups (n = 14 per group): glove electrode;
      placebo TENS using a glove electrode; standard electrode; and no treatment
      control. Active TENS (continuous stimulus, 100 Hz, strong but comfortable
      intensity) was applied to the dominant forearm/hand for 30 minutes. Placebo TENS
      was applied using a burst stimulus, 100-Hz frequency, 5-second cycle time for 42
      seconds, after which the current amplitude was automatically reset to 0 mA.
      Pressure pain thresholds (PPTs) were recorded from 3 points on the dominant and
      nondominant upper limbs before and after TENS. Statistical analyses of dominant
      PPT data using between-within groups ANOVA showed significant differences between
      groups at all 3 recording points (P = .01). Post hoc Scheffe tests indicated no
      significant difference between the standard electrode and glove electrode groups.
      There was a significant hypoalgesic effect in the standard electrode group
      compared with the control group and between the glove electrode group and both
      the control and placebo TENS groups. There was no significant interactive effect
      between time and group at any of the recording points (P > .05). PERSPECTIVE:
      This study presents a comparison of the hypoalgesic effects of 2 different types
      of TENS electrode, a novel glove electrode and standard self-adhesive rectangular
      electrodes. The glove electrode provides a larger contact area with the skin,
      thereby stimulating a greater number of nerve fibers. The results show that both
      electrodes have similar hypoalgesic effects and therefore give the clinician
      another choice in electrode.

PMID- 19398379
TI  - Analgesics administered during minor painful procedures in a cohort of
      hospitalized infants: a prospective clinical audit.
AB  - A number of evidence-based consensus statements relating to pain in infants
      include recommendations concerning effective pain management during painful
      procedures. Yet numerous studies have shown that procedural pain remains poorly
      managed in neonatal intensive care units. The aim of this prospective clinical
      audit was to ascertain analgesics administered during skin-breaking, minor
      painful procedures occurring over the entire course of a hospitalization in a
      cohort of infants with a length of stay of 28 days or more. Data were collected
      on aspects relating to utilization of oral sucrose specifically for minor painful
      procedures as well as administration of opioid analgesics or other strong
      analgesics on the day the procedures were performed. A total of 3605 minor
      painful procedures were recorded for 55 infants during the study period, a mean
      of 65 minor procedures per infant. The majority of procedures recorded were heel
      lance (71%), followed by intravenous catheter insertion or venepuncture (14%).
      Either oral sucrose was specifically administered or background opioid analgesics
      were being administered during 85% of all minor painful procedures. These results
      show considerably higher frequency of analgesic use during acute minor painful
      procedures compared with similar studies of pain management practices in neonatal
      intensive care units. PERSPECTIVE: This study ascertained analgesics administered
      to sick infants during minor painful procedures during a prolonged
      hospitalization. Oral sucrose or morphine was administered during the most
      painful procedures, whereas 15% of procedures were performed with no analgesics.
      This illustrates a vast improvement compared with similar studies.

PMID- 19398380
TI  - Increased phosphorylation of extracellular signal-regulated kinase in trigeminal
      nociceptive neurons following propofol administration in rats.
AB  - Although propofol (PRO) is widely used in clinic as a hypnotic agent, the
      underlying mechanisms of its action on pain pathways is still unknown. Sprague
      Dawley rats were assigned to receive PRO or pentobarbital (PEN) and were divided
      into 2 groups as LIGHT and DEEP hypnotic levels based on the EEG analysis. Rats
      in each hypnotic level received capsaicin injection into the face and
      phosphorylated extracellular signal-regulated kinase (pERK) immunohistochemistry
      was performed in subnucleus caudalis (Vc) and upper cervical spinal cord. In the
      rats with PEN or PRO administration, a large number of pERK-like immunoreactive
      (LI) cells was observed in the trigeminal spinal subnuclei interpolaris and
      caudalis transition zone (Vi/Vc), middle Vc, and transition zone between Vc and
      upper cervical spinal cord (Vc/C2) following capsaicin injection into the whisker
      pad region. The number of pERK-LI cells in Vi/Vc, middle Vc, and Vc/C2 was
      significantly larger in rats with PRO infusion than those with PEN infusion. The
      number of pERK-LI cells was increased following an increase in the dose of PRO
      but not in PEN. The pERK-LI cells were mainly distributed in the Vi/Vc, middle
      Vc, and Vc/C2 after the bolus infusion of PRO. The expression of pERK-LI cells
      was depressed after the intravenous lidocaine application before bolus PRO
      infusion. The present findings suggest that PRO induced an enhancement of the
      activity of trigeminal nociceptive pathways through nociceptors innervating the
      venous structure, as indicated by a lidocaine-sensitive increase in pERK. This
      may explain deep pain around the injection regions during intravenous bolus
      infusion of PRO. PERSPECTIVE: The effect of propofol administration on ERK
      phosphorylation in the subregions of the spinal trigeminal complex and upper
      cervical spinal cord neurons were precisely analyzed in rats with PRO infusion. A
      large number of pERK-LI cells was observed following intravenous PRO
      administration, suggesting an enhancement of trigeminal nociceptive activity and
      that PRO may produce pain through nociceptors innervating the venous structures
      during infusion.

PMID- 19398381
TI  - Long-term benefits of an educational and physical program on headache, and neck
      and shoulder pain, in a working community.
AB  - We previously published the results of a controlled trial that showed the
      efficacy of a workplace educational and physical program in reducing headache,
      and neck and shoulder pain. Participants recorded daily pain episodes in diaries;
      after 2 months of baseline observation, the program was administered to the
      intervention arm only, and comparison with the control arm was performed at month
      8. The objective of the present study was to confirm the long-term (14 months
      from the beginning of the study) benefit of the program in the intervention arm
      of the study (192 office employees). Outcome measures of the present analyses
      were: 1) the number of days/month with headache, and neck and shoulder pain; 2)
      the frequency of days with analgesic drug consumption; 3) the proportion of
      subjects with 4 or more days/month with headache or neck and shoulder pain at
      baseline who achieved a > or =50% reduction in pain (responder rate). Days/month
      with headache decreased from 5.50 at baseline (months 1-2) to 3.11 at months 13
      14 (P < .001); from 6.79 to 3.88 (P < .001) for neck and shoulder pain; and from
      1.72 to 0.86 (P < .001) for analgesic consumption. Responder rates were 58.8%
      (95%CI = 47.1-70.5) for headache, 60.9% (49.4-72.4) for neck and shoulder pain,
      and 68.2 % (48.7-87.6) for drug consumption. These results confirm that the
      program may be effective at long term. PERSPECTIVE: This article presents the
      results at long term of an educational and physical program in reducing headache,
      and neck and shoulder pain, in a working community. Since the benefits remained
      stable for a considerable period of time, a randomized trial is ongoing to
      confirm these results on a larger, less-selected working population.

PMID- 19398382
TI  - Enhanced presurgical pain temporal summation response predicts post-thoracotomy
      pain intensity during the acute postoperative phase.
AB  - Recent evidence points to an association between experimental pain measures
      obtained preoperatively and acute postoperative pain (POP). We hypothesized that
      pain temporal summation (TS) might be an additional predictor for POP insofar as
      it represents the neuroplastic changes that occur in the central nervous system
      following surgery. Therefore, a wide range of psychophysical tests (TS to heat
      and mechanical repetitive stimuli, pain threshold, and suprathreshold pain
      estimation) and personality tests (pain catastrophizing and anxiety levels) were
      administered prior to thoracotomy in 84 patients. POP ratings were evaluated on
      the 2nd and 5th days after surgery at rest (spontaneous pain) and in response to
      activity (provoked pain). Linear regression models revealed that among all
      assessed variables, enhanced TS and higher pain scores for mechanical stimulation
      were significantly associated with greater provoked POP intensity (overall r2 =
      0.225, P = .008). Patients who did not demonstrate TS to both modalities reported
      lower scores of provoked POP as compared with patients who demonstrated TS in
      response to at least 1 modality (F = 4.59 P = .013). Despite the moderate
      association between pain catastrophizing and rest POP, none of the variables
      predicted the spontaneous POP intensity. These findings suggest that individual
      susceptibility toward a greater summation response may characterize patients who
      are potentially vulnerable to augmented POP. PERSPECTIVE: This study proposed the
      role of pain temporal summation assessed preoperatively as a significant
      psychophysical predictor for acute postoperative pain intensity. The individual
      profile of enhanced pain summation is associated with the greater likelihood of
      higher postoperative pain scores.

PMID- 19398383
TI  - Comorbid chronic pain and depression: who is at risk?
AB  - The purpose of this study was to investigate the prevalence and demographic risk
      factors of chronic pain and its comorbidity with depression. Computer-assisted
      telephone interviewing was utilized to obtain a representative community sample
      in the state of Michigan (n = 1,179). The prevalence of chronic pain due to any
      cause was 21.9%. Approximately 35% of participants with chronic pain also had
      comorbid depression (7.7% of the entire sample). Depression was not associated
      with pain types or sites. A multinomial-regression analysis revealed several
      demographic correlates of chronic pain and depression. Participants with chronic
      pain or comorbid pain and depression were more likely to be older, female,
      employed less than full-time, and have less education than persons without either
      condition. Logistic regression analyses showed that younger participants were
      more likely to have comorbid pain and depression than chronic pain only. A
      similar but marginally significant effect was found for African American
      participants. Compared to the depression-only group, those in the comorbid group
      were more likely to be women and middle-aged. These findings provide additional
      evidence on the prevalence of comorbid pain and depression in the community and
      suggest that certain demographic groups with chronic pain may especially benefit
      from depression screenings. PERSPECTIVE: This article reports on the prevalence
      of chronic pain and co-occurring depression in a representative community sample.
      The high prevalence rates of pain and comorbid depression point to the clinical
      importance of assessing depression in chronic pain samples.

PMID- 19398384
TI  - Personal values and pain tolerance: does a values intervention add to acceptance?
AB  - Previous research suggests that acceptance is a promising alternative to
      distraction and control techniques in successfully coping with pain. Acceptance
      interventions based upon Acceptance and Commitment Therapy (ACT) have been shown
      to lead to greater tolerance of acute pain as well as increased adjustment and
      less disability among individuals with chronic pain. However, in these previous
      intervention studies, the ACT component of values has either not been included or
      not specifically evaluated. The current study compares the effects of an ACT
      based acceptance intervention with and without the values component among
      individuals completing the cold-pressor task. Results indicate that inclusion of
      the values component (n = 34) of ACT leads to significantly greater pain
      tolerance than acceptance alone (n = 30). Consistent with previous research, both
      conditions were associated with greater pain tolerance than control (n = 35).
      Despite the difference in tolerance, pain threshold did not differ, and
      participants in the control condition provided lower ratings of pain severity.
      The findings from this study support the important role of values and values
      clarification in acceptance-based interventions such as ACT, and provide
      direction for clinicians working with individuals with chronic pain conditions.
      PERSPECTIVE: This article evaluates the additive effect of including a
      personalized-values exercise in an acceptance-based treatment for pain. Results
      indicate that values interventions make a significant contribution and
      improvement to acceptance interventions, which may be of interest to clinicians
      who provide psychological treatment to individuals with chronic pain.

PMID- 19398385
TI  - Surgical management of superficial siderosis.
AB  - BACKGROUND CONTEXT: Superficial siderosis is a rare condition resulting from the
      presence of chronic bleeding into the subarachnoid space usually causing gait
      instability and deafness. The surgical management of superficial siderosis
      depends on localizing the source of hemorrhage. PURPOSE: The surgical treatment
      of this rare condition has not been well described in the literature. We present
      a case illustrating the surgical treatment for superficial siderosis. STUDY
      DESIGN: Case report. PATIENT SAMPLE: The authors describe the case report of a 70
      year-old gentleman with gait instability and deafness found to have an abnormal
      communication between the spinal epidural venous plexus and the subarachnoid
      space. METHODS: The source of hemorrhage into the subarachnoid space was
      identified to be a fistula in the ventral thoracic dural. A costotransversectomy
      approach was undertaken at the T4-T5 level to expose the fistula. The abnormal
      communication was patched and sealed. RESULTS: The patient's symptoms remained
      stable on follow-up at 15 months with no worsening of his symptoms. CONCLUSIONS:
      Superficial siderosis is a neurologic disorder that arises from chronic
      hemosiderin deposition into the subarachnoid space. The progressive nature of the
      disease can be halted if a source of hemorrhage can be found and treated
      surgically.

PMID- 19398386
TI  - Spinal stenosis prevalence and association with symptoms: the Framingham Study.
AB  - BACKGROUND CONTEXT: The prevalence of lumbar spinal stenosis (LSS) in the general
      population and association with low back pain (LBP) remain unclear. PURPOSE: To
      evaluate the prevalence of congenital and acquired LSS observed on computed
      tomography in a community-based sample; and to evaluate the association between
      LSS and LBP. STUDY DESIGN/SETTING: Cross-sectional observational study. This
      study was an ancillary project to the Framingham Heart Study. PATIENT SAMPLE: A
      total of 3,529 participants underwent multidetector computed tomography; 191 were
      enrolled in this study. OUTCOME MEASURES: Self-report measures: LBP in the
      preceding 12 months was evaluated using a self-report questionnaire. Physiologic
      measures: LSS (congenital and acquired) was characterized using two cut-points:
      12mm for relative LSS and 10mm for absolute LSS. METHODS: Using multiple logistic
      regression, we examined the association between LSS and LBP, adjusting for sex,
      age, and body mass index. RESULTS: In the congenital group, relative LSS was
      found in 4.7% and absolute LSS in 2.6% of patients. Acquired LSS was found in
      22.5% and in 7.3%, respectively. Acquired LSS showed increasing prevalence with
      age less than 40 years, the prevalence of relative and absolute LSS was 20.0% and
      4.0%, respectively, and in those 60 to 69 years the prevalence was 47.2% and
      19.4%, respectively. The presence of absolute LSS was associated with LBP with an
      odds ratio of 3.16 (95% confidence interval [CI]: 1.05-9.53). CONCLUSIONS: The
      prevalence of congenital and acquired LSS in a community-based sample was
      characterized. The prevalence of acquired stenosis increased with age. LSS is
      associated with a threefold higher risk of experiencing LBP.

PMID- 19398387
TI  - Influence of lumbar epidural injection volume on pain relief for radicular leg
      pain and/or low back pain.
AB  - BACKGROUND CONTEXT: Epidural injections are commonly used to treat low back
      disorders. It has been proposed that in addition to the anti-inflammatory
      effects, injected material displaces the dura forward and inward, producing a
      stretch of the nerve roots that leads to lysis of neural adhesions. Despite this,
      there are no controlled trials investigating the effect of volume injected with
      pain as an independent outcome. PURPOSE: Review the existing literature to assess
      the effect of epidural injection volume on relief of radicular leg and low back
      pain. STUDY DESIGN: A systematic review of published clinical trials to assess
      the correlation between volume of epidural injection and relief of radicular leg
      and low back pain. METHODS: We searched MEDLINE (1966 to January 2009), EMBASE
      (1980 to January 2009), The Cochrane Library, and the reference lists of
      retrieved articles. The literature search was limited to English and Human
      subjects. Studies were included if they involved the following: 1) a controlled
      clinical trial; 2) epidural injections in treatment groups compared with control
      injections; 3) the same approach to epidural space in both groups; and 4) pain
      relief as an independent outcome. Trials that measured pain relief for radicular
      leg and low back pain, before and after epidural injections were included. Using
      the Cochrane Back Review Group recommendations, pain relief data were extracted
      independently by two reviewers into four categories: immediate (<or=6 weeks);
      short-term (>6 weeks-3 months); intermediate (>or=3 months-1 year); and long-term
      (>or=1 year). Common effect sizes were calculated for each data point. Quality of
      the trials was assessed (two independent authors) using the 11-item criteria list
      recommended in the method guidelines for systematic reviews for the Cochrane Back
      Review Group. The data were analyzed by calculating the following: correlations
      between volume difference and effect size at each data point; and comparing the
      average effect sizes in the studies with same volume in both groups to ones with
      different volumes. RESULTS: Fifteen studies fulfilled the inclusion/exclusion
      criteria. The correlation between volume difference and pain relief was 0.8027
      (p=.002) for the immediate category, 0.5019 (p=.168) for the short-term category,
      and 0.9470 (p=.014) for the intermediate category. Insufficient data were
      available to calculate the correlation coefficient in the long-term category.
      There was a statistically significant difference when comparing the mean effect
      size where the volume injected was the same between the two groups (mean,
      standard deviation [SD]: 0.07, -0.26) with those where the volumes were different
      between comparison groups (mean, SD: 0.81, -0.6), irrespective of the medications
      injected. CONCLUSIONS: These preliminary results suggest a positive correlation
      between larger volumes of fluid injected in the epidural space and greater relief
      of radicular leg pain and/or low back pain. Clinicians should not change their
      practice, until further high-quality clinical studies confirm these findings.

PMID- 19398388
TI  - Estimation of allele frequency in pooled DNA by using PCR-RFLP combined with
      microchip electrophoresis.
AB  - Biallelic marker, most commonly single nucleotide polymorphism (SNP), is widely
      utilized in genetic association analysis, which can be speeded up by estimating
      allele frequency in pooled DNA instead of individual genotyping. Several methods
      have shown high accuracy and precision for allele frequency estimation in pools.
      Here, we explored PCR restriction fragment length polymorphism (PCR-RFLP)
      combined with microchip electrophoresis as a possible strategy for allele
      frequency estimation in DNA pools. We have used the commercial available Agilent
      2100 microchip electrophoresis analysis system for quantifying the enzymatically
      digested DNA fragments and the fluorescence intensities to estimate the allele
      frequencies in the DNA pools. In this study, we have estimated the allele
      frequencies of five SNPs in a DNA pool composed of 141 previously genotyped
      health controls and a DNA pool composed of 96 previously genotyped gastric cancer
      patients with a frequency representation of 10-90% for the variant allele. Our
      studies show that accurate, quantitative data on allele frequencies, suitable for
      investigating the association of SNPs with complex disorders, can be estimated
      from pooled DNA samples by using this assay. This approach, being independent of
      the number of samples, promises to drastically reduce the labor and cost of
      genotyping in the initial association analysis.

PMID- 19398389
TI  - Simultaneous drug release at different rates from biodegradable polyurethane
      foams.
AB  - In this study, we present an approach for the simultaneous release of multiple
      drug compounds at different rates from single-phase polyurethane foams
      constructed from lysine diisocyanate (LDI) and glycerol. The anti-cancer
      compounds DB-67 and doxorubicin were covalently incorporated into polyurethane
      foams, whereby drug release can then occur in concert with material degradation.
      To begin, the reactions of DB-67 and doxorubicin with LDI in the presence of a
      tertiary amine catalyst were monitored with infrared spectroscopy; each compound
      formed urethane linkages with LDI. Fluorescent spectra of DB-67 and doxorubicin
      were then recorded in phosphate-buffered saline, pH 7.4 (PBS), to ensure that
      each anti-cancer compound could be quantitatively detected alone and in
      combination. Doxorubicin and DB-67 were then incorporated into a series of
      degradable LDI-glycerol polyurethane foams alone and in combination with one
      another. The sol content, average porosity and drug distribution throughout each
      foam sample was measured and found to be similar amongst all foam samples. The
      stability of DB-67 and doxorubicin's fluorescent signal was then assessed over a
      2-week period at 70 degrees C. Release rates of the compounds from the foams were
      assessed over a 10-week period at 4, 22, 37 and 70 degrees C by way of
      fluorescence spectroscopy. Release was found to be temperature-dependent, with
      rates related to the chemical structure of the incorporated drug. This study
      demonstrates that differential release of covalently bound drugs is possible from
      simple single-phase, degradable polyurethane foams.

PMID- 19398390
TI  - Inhibition of LPS-induced proinflammatory responses of J774.2 macrophages by
      immobilized enzymatically tailored pectins.
AB  - The surface of an implant device can be modified by immobilizing biological
      molecules on it to improve its integration into the host tissue. We have
      previously demonstrated that enzymatically tailored plant pectins are promising
      nanocoatings for biomaterials. This study investigates whether a coating of
      modified hairy region (rhamnogalacturonan-I) from apple pectin (MHR-alpha) which
      has anti-adhesive properties can inhibit the generation of inflammatory mediators
      by lipopolysaccharide (LPS)-activated macrophages. For that purpose, J774.2
      murine macrophages were cultured for 24h on MHR-alpha-coated Petri dishes and
      tissue culture polystyrene controls, with and without LPS. Cell morphology, cell
      growth, nitrite and TNF-alpha secretion were studied. The results indicate that
      MHR-alpha coating inhibits the LPS-induced activation of macrophages.

PMID- 19398391
TI  - Patterned and switchable surfaces for biomolecular manipulation.
AB  - The interactions of biomolecules and cells with solid interfaces play a pivotal
      role in a range of biomedical applications and have therefore been studied in
      great detail. An improved understanding of these interactions results in the
      ability to manipulate DNA, proteins and other biomolecules, as well as cells,
      spatially and temporally at surfaces with high precision. This in turn engenders
      the development of advanced devices, such as biosensors, bioelectronic
      components, smart biomaterials and microarrays. Spatial control can be achieved
      by the production of patterned surface chemistries using modern high-resolution
      patterning technologies based on lithography, microprinting or microfluidics,
      whilst temporal control is accessible through the application of switchable
      surface architectures. The combination of these two surface properties offers
      unprecedented control over the behaviour of biomolecules and cells at the solid
      liquid interface. This review discusses the behaviour of biomolecules and cells
      at solid interfaces and highlights fundamental and applied research exploring
      patterned and switchable surfaces.

PMID- 19398392
TI  - Novel silk sericin/gelatin 3-D scaffolds and 2-D films: fabrication and
      characterization for potential tissue engineering applications.
AB  - In this study, we report for the first time the fabrication of novel 3-D
      sericin/gelatin scaffolds and 2-D films using non-mulberry Antheraea mylitta silk
      cocoon sericin protein. The matrices were fabricated, biophysically characterized
      and optimized for cell culture applications. Blended sericin/gelatin 3-D
      scaffolds were highly porous with an optimum pore size of 170+/-20 microm. The
      scaffolds were robust with enhanced mechanical strength and showed high
      compressibility. Swelling studies showed high swellability along with complete
      degradation in the presence of phosphate-buffered saline. Cytocompatibility of
      the matrices was evaluated using feline fibroblasts showing normal spreading and
      proliferation as assessed by fluorescence microscopy. Cell cycle analysis showed
      cytocompatibility without any cell cycle arrests. Low immunogenicity of the
      matrices as observed through tumor necrosis factor alpha release reveal its
      potential as future biopolymeric graft material. The results of this novel study
      lay the foundation for the use of the silk cocoon protein sericin as a
      biocompatible biopolymer for tissue engineering applications.

PMID- 19398393
TI  - In vitro bioactivity of bioresorbable porous polymeric scaffolds incorporating
      hydroxyapatite microspheres.
AB  - Biomimetic composites consisting of polymer and mineral components, resembling
      bone in structure and composition, were produced using a rapid prototyping
      technique for bone tissue engineering applications. Solid freeform fabrication,
      known as rapid prototyping (RP) technology, allows scaffolds to be designed with
      pre-defined and controlled external and internal architecture. Using the indirect
      RP technique, a three-component scaffold with a woodpile structure, consisting of
      poly-L-lactic acid (PLLA), chitosan and hydroxyapatite (HA) microspheres, was
      produced that had a macroporosity of more than 50% together with micropores
      induced by lyophilization. X-ray diffraction analysis indicated that the
      preparation and construction of the composite scaffold did not affect the phase
      composition of the HA. The compressive strength and elastic modulus (E) for the
      PLLA composites are 0.42 and 1.46 MPa, respectively, which are much higher than
      those of chitosan/HA composites and resemble the properties of cellular
      structure. These scaffolds showed excellent biocompatibility and ability for
      three-dimensional tissue growth of MC3T3-E1 pre-osteoblastic cells. The pre
      osteoblastic cells cultured on these scaffolds formed a network on the HA
      microspheres and proliferated not only in the macropore channels but also in the
      micropores, as seen from the histological analysis and electron microscopy. The
      proliferating cells formed an extracellular matrix network and also
      differentiated into mature osteoblasts, as indicated by alkaline phosphatase
      enzyme activity. The properties of these scaffolds indicate that they can be used
      for non-load-bearing applications.

PMID- 19398394
TI  - Evaluation of appearance transfer and persistence in central face
      transplantation: a computer simulation analysis.
AB  - BACKGROUND: Partial facial allotransplantation is an emerging option in
      reconstruction of central facial defects, providing function and aesthetic
      appearance. Ethical debate partly stems from uncertainty surrounding identity
      aspects of the procedure. There is no objective evidence regarding the effect of
      donors' transplanted facial structures on appearance change of the recipients and
      its influence on facial recognition of donors and recipients. METHODS: Full-face
      frontal view color photographs of 100 volunteers were taken at a distance of 150
      cm with a digital camera (Nikon/DX80). Photographs were taken in front of a blue
      background, and with a neutral facial expression. Using image-editing software
      (Adobe-Photoshop-CS3), central facial transplantation was performed between
      participants. Twenty observers performed a familiar 'facial recognition task', to
      identify 40 post-transplant composite faces presented individually on the screen
      at a viewing distance of 60 cm, with an exposure time of 5s. Each composite face
      comprised of a familiar and an unfamiliar face to the observers. Trials were done
      with and without external facial features (head contour, hair and ears). Two
      variables were defined: 'Appearance Transfer' refers to transfer of donor's
      appearance to the recipient. 'Appearance Persistence' deals with the extent of
      recipient's appearance change post-transplantation. A t-test was run to determine
      if the rates of Appearance Transfer differed from Appearance Persistence.
      RESULTS: Average Appearance Transfer rate (2.6%) was significantly lower than
      Appearance Persistence rate (66%) (P<0.001), indicating that donor's appearance
      transfer to the recipient is negligible, whereas recipients will be identified
      the majority of the time. External facial features were important in facial
      recognition of recipients, evidenced by a significant rise in Appearance
      Persistence from 19% in the absence of external features to 66% when those
      features were present (P<0.01). CONCLUSION: This study may be helpful in the
      informed consent process of prospective recipients. It is beneficial for
      education of donors families and is expected to positively affect their decision
      to consent for facial tissue donation.

PMID- 19398395
TI  - Topical herbal remedies: research opportunities for plastic surgeons.
AB  - The use of topical herbal remedies (THRs) among plastic surgery patients is
      rampant, sometimes indiscriminately, and expanding rapidly. Supporting scientific
      evidence is low, and most patients who use THRs believe firmly that being
      'natural', these agents are 'safe'. The federal regulation of THRs is not
      uniform. The research potential of these remedies is underexplored, creating a
      vast opportunity for plastic surgeons to harvest its clinical benefits and help
      create a regulatory structure that promotes patient safety. This article
      delineates the critical aspects: essential steps in starting research in THRs,
      organisational structure to support this work including funding sources,
      intellectual property and patent protection, federal regulation and patient
      education and advocacy. These steps create a platform for plastic surgeons to
      pursue this research work and translate it into the clinical setting effectively.

PMID- 19398397
TI  - B-type natriuretic peptides.

PMID- 19398398
TI  - Rehabilitation of arm function after stroke. Literature review.
AB  - INTRODUCTION: In the recent literature we can find many articles dealing with
      upper extremity rehabilitation in stroke patients. New techniques, still under
      evaluation, are becoming the practical applications for the concept of post
      stroke brain plasticity. METHODS: This literature review focuses on controlled
      randomized studies, reviews and meta-analyses published in the English language
      from 2004 to 2008. The research was conducted in MEDLINE with the following
      keywords: "upper limb", "stroke", "rehabilitation". RESULTS: We reviewed 66
      studies. The main therapeutic strategies are: activation of the ipsilesional
      motor cortex, inhibition of the contralesional motor cortex and modulation of the
      sensory afferents. Keeping a cortical representation of the upper limb distal
      extremity could prevent the learned non-use phenomenon. The modulation of sensory
      afferents is then proposed: distal cutaneous electrostimulation, anesthesia of
      the healthy limb, mirror therapy, virtual reality. Intensifying the
      rehabilitation care means increasing the total hours of rehabilitation dedicated
      to the paretic limb (proprioceptive stimulation and repetitive movements). This
      specific rehabilitation is facilitated by robot-aided therapy in the active
      assisted mode, neuromuscular electrostimulation and bilateral task training.
      Intensifying the rehabilitation training program significantly improves the arm
      function outcome when performed during subacute stroke rehabilitation (< six
      months). Ipsilesional neurostimulation as well as mental practice optimize the
      effect of repetitive gestures for slight motor impairments. Contralesional
      neurostimulation or anesthesia of the healthy hand both improve the paretic
      hand's dexterity via a decrease of the transcallosal inhibition. This
      pathophysiological mechanism could also explain the positive impact of constraint
      induced movement therapy (CI therapy) in an environmental setting for chronic
      stroke patients. CONCLUSION: To ensure a positive functional outcome, stroke
      rehabilitation programs are based on task-oriented repetitive training. This
      literature review shows that exercising the hemiparetic hand and wrist is
      essential in all stages of a stroke rehabilitation program. New data stemming
      from neurosciences suggest that ipsilesional corticospinal excitability should be
      a priority.

PMID- 19398399
TI  - Generation of induced pluripotent stem cells using recombinant proteins.

PMID- 19398400
TI  - Comparison of conventional filtering and independent component analysis for
      artifact reduction in simultaneous gastric EMG and magnetogastrography from
      porcines.
AB  - In this study, we perform a comparative study of independent component analysis
      (ICA) and conventional filtering (CF) for the purpose of artifact reduction from
      simultaneous gastric EMG and magnetogastrography (MGG). EMG/MGG data were
      acquired from ten anesthetized pigs by obtaining simultaneous recordings using
      serosal electrodes (EMG) as well as with a superconducting quantum interference
      device biomagnetometer (MGG). The analysis of MGG waveforms using ICA and CF
      indicates that ICA is superior to the CF method in its ability to extract
      respiration and cardiac artifacts from MGG recordings. A signal frequency
      analysis of ICA- and CF-processed data was also undertaken using waterfall plots,
      and it was determined that the two methods produce qualitatively comparable
      results. Through the use of simultaneous EMG/MGG, we were able to demonstrate the
      accuracy and trustworthiness of our results by comparison and cross-validation
      within the framework of a porcine model.

PMID- 19398401
TI  - A neural network model to minimize the connected dominating set for self
      configuration of wireless sensor networks.
AB  - A wireless ad hoc sensor network consists of a number of sensors spreading across
      a geographical area. The performance of the network suffers as the number of
      nodes grows, and a large sensor network quickly becomes difficult to manage.
      Thus, it is essential that the network be able to self-organize. Clustering is an
      efficient approach to simplify the network structure and to alleviate the
      scalability problem. One method to create clusters is to use weakly connected
      dominating sets (WCDSs). Finding the minimum WCDS in an arbitrary graph is an NP
      complete problem. We propose a neural network model to find the minimum WCDS in a
      wireless sensor network. We present a directed convergence algorithm. The new
      algorithm outperforms the normal convergence algorithm both in efficiency and in
      the quality of solutions. Moreover, it is shown that the neural network is
      robust. We investigate the scalability of the neural network model by testing it
      on a range of sized graphs and on a range of transmission radii. Compared with
      Guha and Khuller's centralized algorithm, the proposed neural network with
      directed convergency achieves better results when the transmission radius is
      short, and equal performance when the transmission radius becomes larger. The
      parallel version of the neural network model takes time O(d), where d is the
      maximal degree in the graph corresponding to the sensor network, while the
      centralized algorithm takes O(n2). We also investigate the effect of the
      transmission radius on the size of WCDS. The results show that it is important to
      select a suitable transmission radius to make the network stable and to extend
      the lifespan of the network. The proposed model can be used on sink nodes in
      sensor networks, so that a sink node can inform the nodes to be a coordinator
      (clusterhead) in the WCDS obtained by the algorithm. Thus, the message overhead
      is O(M), where M is the size of the WCDS.

PMID- 19398402
TI  - Associative memory for online learning in noisy environments using self
      organizing incremental neural network.
AB  - Associative memory operating in a real environment must perform well in online
      incremental learning and be robust to noisy data because noisy associative
      patterns are presented sequentially in a real environment. We propose a novel
      associative memory that satisfies these requirements. Using the proposed method,
      new associative pairs that are presented sequentially can be learned accurately
      without forgetting previously learned patterns. The memory size of the proposed
      method increases adaptively with learning patterns. Therefore, it suffers neither
      redundancy nor insufficiency of memory size, even in an environment in which the
      maximum number of associative pairs to be presented is unknown before learning.
      Noisy inputs in real environments are classifiable into two types: noise-added
      original patterns and faultily presented random patterns. The proposed method
      deals with two types of noise. To our knowledge, no conventional associative
      memory addresses noise of both types. The proposed associative memory performs as
      a bidirectional one-to-many or many-to-one associative memory and deals not only
      with bipolar data, but also with real-valued data. Results demonstrate that the
      proposed method's features are important for application to an intelligent robot
      operating in a real environment. The originality of our work consists of two
      points: employing a growing self-organizing network for an associative memory,
      and discussing what features are necessary for an associative memory for an
      intelligent robot and proposing an associative memory that satisfies those
      requirements.

PMID- 19398403
TI  - Probabilistic classification vector machines.
AB  - In this paper, a sparse learning algorithm, probabilistic classification vector
      machines (PCVMs), is proposed. We analyze relevance vector machines (RVMs) for
      classification problems and observe that adopting the same prior for different
      classes may lead to unstable solutions. In order to tackle this problem, a signed
      and truncated Gaussian prior is adopted over every weight in PCVMs, where the
      sign of prior is determined by the class label, i.e., +1 or -1. The truncated
      Gaussian prior not only restricts the sign of weights but also leads to a sparse
      estimation of weight vectors, and thus controls the complexity of the model. In
      PCVMs, the kernel parameters can be optimized simultaneously within the training
      algorithm. The performance of PCVMs is extensively evaluated on four synthetic
      data sets and 13 benchmark data sets using three performance metrics, error rate
      (ERR), area under the curve of receiver operating characteristic (AUC), and root
      mean squared error (RMSE). We compare PCVMs with soft-margin support vector
      machines (SVM(Soft)), hard-margin support vector machines (SVM(Hard)), SVM with
      the kernel parameters optimized by PCVMs (SVM(PCVM)), relevance vector machines
      (RVMs), and some other baseline classifiers. Through five replications of twofold
      cross-validation F test, i.e., 5 x 2 cross-validation F test, over single data
      sets and Friedman test with the corresponding post-hoc test to compare these
      algorithms over multiple data sets, we notice that PCVMs outperform other
      algorithms, including SVM(Soft), SVM(Hard), RVM, and SVM(PCVM), on most of the
      data sets under the three metrics, especially under AUC. Our results also reveal
      that the performance of SVM(PCVM) is slightly better than SVM(Soft), implying
      that the parameter optimization algorithm in PCVMs is better than cross
      validation in terms of performance and computational complexity. In this paper,
      we also discuss the superiority of PCVMs' formulation using maximum a posteriori
      (MAP) analysis and margin analysis, which explain the empirical success of PCVMs.

PMID- 19398404
TI  - Self-organizing CMAC control for a class of MIMO uncertain nonlinear systems.
AB  - This paper presents a self-organizing control system based on cerebellar model
      articulation controller (CMAC) for a class of multiple-input-multiple-output
      (MIMO) uncertain nonlinear systems. The proposed control system merges a CMAC and
      sliding-mode control (SMC), so the input space dimension of CMAC can be
      simplified. The structure of CMAC will be self-organized; that is, the layers of
      CMAC will grow or prune systematically and their receptive functions can be
      automatically adjusted. The control system consists of a self-organizing CMAC
      (SOCM) and a robust controller. SOCM containing a CMAC uncertainty observer is
      used as the principal controller and the robust controller is designed to dispel
      the effect of approximation error. The gradient-descent method is used to online
      tune the parameters of CMAC and the Lyapunov function is applied to guarantee the
      stability of the system. A simulation study of inverted double pendulums system
      and an experimental result of linear ultrasonic motor motion control show that
      favorable tracking performance can be achieved by using the proposed control
      system.

PMID- 19398405
TI  - A high-capacity steganography scheme for JPEG2000 baseline system.
AB  - Hiding capacity is very important for efficient covert communications. For
      JPEG2000 compressed images, it is necessary to enlarge the hiding capacity
      because the available redundancy is very limited. In addition, the bitstream
      truncation makes it difficult to hide information. In this paper, a high-capacity
      steganography scheme is proposed for the JPEG2000 baseline system, which uses bit
      plane encoding procedure twice to solve the problem due to bitstream truncation.
      Moreover, embedding points and their intensity are determined in a well defined
      quantitative manner via redundancy evaluation to increase hiding capacity. The
      redundancy is measured by bit, which is different from conventional methods which
      adjust the embedding intensity by multiplying a visual masking factor. High
      volumetric data is embedded into bit-planes as low as possible to keep message
      integrality, but at the cost of an extra bit-plane encoding procedure and
      slightly changed compression ratio. The proposed method can be easily integrated
      into the JPEG2000 image coder, and the produced stego-bitstream can be decoded
      normally. Simulation shows that the proposed method is feasible, effective, and
      secure.

PMID- 19398406
TI  - Semi-automatically labeling objects in images.
AB  - Labeling objects in images plays a crucial role in many visual learning and
      recognition applications that need training data, such as image retrieval, object
      detection and recognition. Manually creating object labels in images is time
      consuming and, thus, becomes impossible for labeling a large image dataset. In
      this paper, we present a family of semi-automatic methods based on a graph-based
      semi-supervised learning algorithm for labeling objects in images. We first
      present SmartLabel that proposes to label images with reduced human input by
      iteratively computing the harmonic solutions to minimize a quadratic energy
      function on the Gaussian fields. SmartLabel tackles the problem of lacking
      negative data in the learning by embedding relevance feedback after the first
      iteration, which also leads to one limitation of SmartLabel-needing additional
      human supervision. To overcome the limitation and enhance SmartLabel, we propose
      SmartLabel-2 that utilizes a novel scheme to sample negative examples
      automatically, replace regular patch partitioning in SmartLabel by quadtree
      partitioning and applies image over-segmentation (superpixels) to extract smooth
      object contours. Evaluation on six diverse object categories have indicated that
      SmartLabel-2 can achieve promising results with a small amount of labeled data
      (e.g., 1%-5% of image size) and obtain close-to-fine extraction of object
      contours on different kinds of objects.

PMID- 19398407
TI  - Hierarchical segmentation-based image coding using hybrid quad-binary trees.
AB  - A novel segmentation-based image approximation and coding technique is proposed.
      A hybrid quad-binary (QB) tree structure is utilized to efficiently model and
      code geometrical information within images. Compared to other tree-based
      representation such as wedgelets, the proposed QB-tree based method is more
      efficient for a wide range of contour features such as junctions, corners and
      ridges, especially at low bit rates.

PMID- 19398408
TI  - Removal of correlated noise by modeling the signal of interest in the wavelet
      domain.
AB  - Images, captured with digital imaging devices, often contain noise. In
      literature, many algorithms exist for the removal of white uncorrelated noise,
      but they usually fail when applied to images with correlated noise. In this
      paper, we design a new denoising method for the removal of correlated noise, by
      modeling the significance of the noise-free wavelet coefficients in a local
      window using a new significance measure that defines the "signal of interest" and
      that is applicable to correlated noise. We combine the intrascale model with a
      hidden Markov tree model to capture the interscale dependencies between the
      wavelet coefficients. We propose a denoising method based on the combined model
      and a less redundant wavelet transform. We present results that show that the new
      method performs as well as the state-of-the-art wavelet-based methods, while
      having a lower computational complexity.

PMID- 19398409
TI  - Rate-invariant recognition of humans and their activities.
AB  - Pattern recognition in video is a challenging task because of the multitude of
      spatio-temporal variations that occur in different videos capturing the exact
      same event. While traditional pattern-theoretic approaches account for the
      spatial changes that occur due to lighting and pose, very little has been done to
      address the effect of temporal rate changes in the executions of an event. In
      this paper, we provide a systematic model-based approach to learn the nature of
      such temporal variations (time warps) while simultaneously allowing for the
      spatial variations in the descriptors. We illustrate our approach for the problem
      of action recognition and provide experimental justification for the importance
      of accounting for rate variations in action recognition. The model is composed of
      a nominal activity trajectory and a function space capturing the probability
      distribution of activity-specific time warping transformations. We use the square
      root parameterization of time warps to derive geodesics, distance measures, and
      probability distributions on the space of time warping functions. We then design
      a Bayesian algorithm which treats the execution rate function as a nuisance
      variable and integrates it out using Monte Carlo sampling, to generate estimates
      of class posteriors. This approach allows us to learn the space of time warps for
      each activity while simultaneously capturing other intra- and interclass
      variations. Next, we discuss a special case of this approach which assumes a
      uniform distribution on the space of time warping functions and show how
      computationally efficient inference algorithms may be derived for this special
      case. We discuss the relative advantages and disadvantages of both approaches and
      show their efficacy using experiments on gait-based person identification and
      activity recognition.

PMID- 19398410
TI  - Electronic noise modeling in statistical iterative reconstruction.
AB  - We consider electronic noise modeling in tomographic image reconstruction when
      the measured signal is the sum of a Gaussian distributed electronic noise
      component and another random variable whose log-likelihood function satisfies a
      certain linearity condition. Examples of such likelihood functions include the
      Poisson distribution and an exponential dispersion (ED) model that can
      approximate the signal statistics in integration mode X-ray detectors. We
      formulate the image reconstruction problem as a maximum-likelihood estimation
      problem. Using an expectation-maximization approach, we demonstrate that a
      reconstruction algorithm can be obtained following a simple substitution rule
      from the one previously derived without electronic noise considerations. To
      illustrate the applicability of the substitution rule, we present examples of a
      fully iterative reconstruction algorithm and a sinogram smoothing algorithm both
      in transmission CT reconstruction when the measured signal contains additive
      electronic noise. Our simulation studies show the potential usefulness of
      accurate electronic noise modeling in low-dose CT applications.

PMID- 19398411
TI  - A novel evolutionary approach to image enhancement filter design: method and
      applications.
AB  - Image enhancement is an important issue in digital image processing. Various
      approaches have been developed to solve image enhancement problems, but most of
      them require deep expert knowledge to design appropriate image filters. To
      automatically design a filter, we propose a novel approach based on the genetic
      algorithm that optimizes a set of standard filters by determining their types and
      order. Moreover, the proposed method is able to manage various types of noise
      factors. We applied the proposed method to local and global image enhancement
      problems such as impulsive noise reduction, interpolation, and orientation
      enhancement. In terms of subjective and objective evaluations, the results show
      the superiority of the proposed method.

PMID- 19398412
TI  - The influence of ambient temperature on power at anaerobic threshold determined
      based on blood lactate concentration and myoelectric signals.
AB  - OBJECTIVES: To compare the mechanical power and physiological parameters in males
      at the lactate (LAAT) and integrated electromyographic (IEMGAT) anaerobic
      thresholds during exercise testing at 23 degrees C, 31 degrees C and 37 degrees
      C. MATERIALS AND METHODS: Fifteen men aged 21.9+/-1.80 years performed an
      incremental exercise test on a cycle ergometer at pedal frequency of 60 rpm. The
      test began at the power output of 120 W which was increased by 30 W every 3 min.
      Heart rate, oxygen uptake, carbon dioxide in expired air and minute ventilation
      were monitored. Venous blood samples were collected at 30 s before termination of
      each 3-min stage of test to determine the lactate anaerobic threshold. IEMGAT for
      vastus lateralis (VL) and rectus femoris (RF) muscles were regarded as the
      inflection point at which a non-linear increase in IEMGAT occurred. RESULTS:
      IEMGAT for VL and RF were similar for all the three temperatures. IEMGAT (VL and
      RF) correlated closely with LAAT at ambient temperatures of 23 degrees C (r =
      0.91), 31 degrees C (r = 0.96) and 37 degrees C (r = 0.97). Repeated measures
      analysis of variance (ANOVA) revealed that the mechanical power at LAAT and
      IEMGAT was higher at 23 degrees C (202+/-26.5 W vs. 205+/-22.9 W) than at 31
      degrees C (186+/-20.2 W vs. 186.2+/-20.2 W) and 37 degrees C (175.5+/-25.2 W vs.
      175.3+/-20.0 W) for LAAT and IEMGAT respectively (p < 0.01). CONCLUSIONS: Higher
      ambient temperature induced a decrease in the mechanical power at which the
      anaerobic threshold occurred. The high correlation between LAAT and IEMGAT (r =
      0.91-0.97) indicated that IEMGAT can be used as a practical and reliable, non
      invasive method for assessment of the anaerobic threshold.

PMID- 19398413
TI  - Assessing the coagulation factor levels, inherited thrombophilia, and ABO blood
      group on the risk for venous thrombosis among Brazilians.
AB  - Increased coagulation factor levels have been demonstrated to be a risk factor
      for venous thromboembolism in patients of Caucasian origin. Coagulation factors,
      hereditary thrombophilia, and ABO blood group were evaluated for venous
      thrombosis risk in a heterogeneous Brazilian population consisting of 122 women
      and 53 men, with a median age of 36 years (range 13-63), matched to a control
      group by age, sex, and ethnicity. Increased levels of factor VIII (odds ratio
      [OR], 3.1; 95% confidence interval [CI], 1.6-6.0), von Willebrand factor (OR,
      2.8; 95% CI, 1.4-5.4), non-O blood group (OR, 2.1; 95% CI, 1.3-3.4), and
      thrombophilia (OR, 3.4; 95% CI, 1.6-7.1) emerged as independent risk factors for
      venous thromboembolism. The interaction of high levels of factor IX and factor XI
      with other independent variables increased the potential for thrombosis
      synergistically. Therefore, the ability of identifying underlying thrombophilia
      risk factors in our population was enhanced by the inclusion of these factors in
      the prothrombotic laboratory workup.

PMID- 19398414
TI  - Genome-wide screen identifies drug-induced regulation of the gene giant axonal
      neuropathy (Gan) in a mouse model of antiretroviral-induced painful peripheral
      neuropathy.
AB  - Painful peripheral neuropathy is a debilitating complication of the treatment of
      HIV with nucleoside reverse transcriptase inhibitors (NRTIs). Patients are living
      longer with these drugs; however many develop excruciating, unremitting, and
      often treatment-limiting neuropathy that is resistant to conventional pain
      management therapies. Improving patient comfort and quality of life is paramount
      and depends on a clearer understanding of this devastating side effect. The
      mechanisms underlying the development of NRTI-induced neuropathy, however, remain
      unclear. Using a mouse model of NRTI-induced neuropathy, the authors conducted an
      unbiased whole-genome microarray screen to identify molecular targets in the
      spinal dorsal horn, which is the location where integration of ascending sensory
      transmission and descending modulatory effects occur. Analysis of the microarray
      data identified a change in the gene giant axonal neuropathy 1 (Gan1). Mutation
      of this gene has been linked to the development of giant axonal neuropathy (GAN),
      a rare autosomal recessive condition characterized by a progressive sensorimotor
      neuropathy. Gan1 has not been previously linked to nerve pathologies in other
      populations. In this study, downregulation of the Gan1 gene and the gene protein
      product, gigaxonin, was validated via quantitative polymerase chain reaction
      ([qPCR] gene expression) and Western blot analyses (protein level). Our report is
      the first to suggest that Gan1 might be a novel molecular target in the
      development of NRTI-induced peripheral neuropathy with implications for new
      therapeutic approaches to preventing or reducing a significant side effect of HIV
      treatment.

PMID- 19398415
TI  - Gene therapy and informed consent decision making: nursing research directions.
AB  - Recent gene therapy clinical trials have demonstrated significant promise for
      treating a number of genetic neuromuscular disorders. Although nurses are
      experienced in educating patients and families about the benefits and risks of
      conventional therapeutics, there are significant challenges for guiding patients
      through the decision-making phase of gene therapy clinical trial participation.
      The first part of this review provides an overview and update on neuromuscular
      gene therapy, including viral delivery principles and historical progress. The
      second part discusses risk/benefit perception of gene therapy and factors
      affecting the decision making for patients interested in participating in a
      trial. Future challenges for gene therapy are targeted high-efficiency delivery,
      and additional research on developing patient-centered decision support
      interventions.

PMID- 19398416
TI  - Intracranial pressure waveform analysis during rest and suctioning.
AB  - Cerebral compliance is a measure of cerebral adaptability to increases in volume
      within the intracranial space and an indicator of risk for neurological
      deterioration. However, no direct measurement of compliance exists in clinical
      practice to guide nursing care or treatment decisions. Current use of mean
      intracranial pressure (MICP) and gross morphological intracranial pressure
      waveform (ICPW) analysis have great variability in predicting outcomes. The
      purpose of this review and pilot study was to evaluate the effects of suctioning
      on MICP and other measures estimating cerebral compliance derived from analysis
      of ICPW on patient outcome. We analyzed arterial blood pressure waveforms
      (ABPWs), ICPWs, and respiratory cycle variations using Fourier Transform
      analysis, to explore the potential benefits of studying ICPWs across single
      cardiac and respiratory cycles using linear modeling and calculation of
      correlation coefficients. ABPWs, ICPWs, and MICP were measured over individual
      cardiac cycles across multiple respiratory phases in five critically ill
      neurological patients. Both direct and derived ICP measures, including Fourier
      analysis of ABP and ICP and the cross-transform between ABP and ICP, were
      correlated with patient outcome. This more complex waveform analysis of
      individual ABPW and ICPW together, and derived measures during both single
      cardiac and respiratory cycles, may provide information relevant to cerebral
      compliance and patient outcomes. Pending confirmation with additional data sets,
      this technique may be a useful real-time clinical tool to provide a measure of
      compliance and risk of neurological deterioration for clinicians.

PMID- 19398417
TI  - Genetic characterization of familial CPVT after 30 years.
AB  - INTRODUCTION: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a
      stress-related, bidirectional ventricular tachycardia and atrial tachyarrhythmia
      in the absence of either structural heart disease or prolonged QT interval.
      Autosomal dominant and recessive forms of CPVT because of mutations in the
      cardiac ryanodine receptor (RyR2) or calsequestrin 2 (CASQ2) have been reported.
      The objective of this study was the clinical and genetic characterization of the
      family of an individual initially diagnosed as a child in 1978. METHOD: We
      collected family medical history and recorded a four-generation pedigree. We
      performed mutation analysis of RyR2 "critical regions'' in the N-terminus,
      FKBP12.6 binding domain, Ca2+ binding domain, and transmembrane domains of the C
      terminus by direct sequencing. RESULTS: CPVT was diagnosed in two of the nine
      family members evaluated. Pedigree analysis suggested autosomal dominant disease
      transmission. There were no additional reports of seizures, pregnancy loss,
      neonatal death, or sudden cardiac death in family members. A novel RyR2 gene
      variant (W4645R) was found in four family members including two without symptoms.
      RyR2-W4645R segregates with disease in this family with incomplete penetrance.
      The W4645 residue is evolutionarily conserved in the transmembrane region
      adjacent to previously reported disease-causing mutations. Based on sorting
      intolerant from tolerant analysis of protein structure, RyR2-W4645R is predicted
      to be deleterious. CONCLUSIONS: All current evidence supports RyR2-W4645R as a
      disease-causing variant, which was silent in persons for two generations before
      causing symptoms in persons for the next two generations, beginning in 1978.

PMID- 19398418
TI  - Peripheral arterial disease and clinical risks in Taiwanese hemodialysis
      patients.
AB  - Peripheral arterial disease (PAD) is associated with significant morbidity and
      mortality and is an important marker of systemic atherosclerosis. However, little
      is known about the associated risk factors for PAD in patients on maintenance
      hemodialysis (HD). We collected the basic data and possible risk factors
      associated with PAD for 277 patients on maintenance HD. Furthermore, we measured
      ankle-brachial blood pressure index (ABI) in these patients. PAD was defined as
      an ABI value less than 0.90. The prevalence of PAD in our HD center was 22.8%
      (61/268). Advanced age (P = 0.006), longer history of HD (P < 0.001), diabetes (P
      = 0.002) and presence of PAD symptoms (P < 0.001) were independent predictors of
      PAD. PAD patients with diabetes had shorter history of HD (P = 0.001). 2-vessel
      PAD had higher serum cholesterol in HD patients (>or= 200 vs < 200 mg/dL; Odds
      ratio, 12.12, 95% confidence interval, 2.199-67.79; P < 0.004).

PMID- 19398419
TI  - Percutaneous revascularization of unprotected left main: results of PCI using
      drug-eluting stent in ostial versus distal bifurcation disease.
AB  - BACKGROUND: Coronary artery bypass graft surgery is standard treatment for
      unprotected left main coronary artery disease. Recently, drug-eluting stents have
      been used to treat unprotected left main coronary artery disease. OBJECTIVE: To
      analyze data for consecutive patients treated at a single center with drug
      eluting stents for unprotected left main coronary artery disease. RESULTS:
      Seventy-three patients underwent elective percutaneous coronary intervention of
      unprotected left main coronary artery disease. Twenty-one (30%) of the patients
      had disease involving the ostium or midshaft of the left main, while the
      remaining 52 (70%) patients had distal bifurcation disease. The group consisted
      of high-risk patients with an average European System for Cardiac Operative Risk
      Evaluation of 9% (range 0.9%-54%). After 1 year follow-up, 3 (4%) patients died;
      8 patients (11%) had target vessel revascularization; 4 with repeat percutaneous
      coronary intervention; and 4 with coronary artery bypass graft surgery. All the
      events occurred in the distal bifurcation group. CONCLUSION: These results from a
      single-center registry suggest the safety of performing percutaneous coronary
      intervention with drug-eluting stents in unprotected left main coronary artery
      disease with low major adverse cardiac events (MACE) rates at 1 year.

PMID- 19398420
TI  - The difficult venous ulcer: case series of 177 ulcers referred for vascular
      surgical opinion following failure of conservative management.
AB  - Venous leg ulcers are common, chronic, debilitating, and expensive. Evidence
      supports use of compression bandaging, with superficial venous surgery in
      selected cases, but these interventions frequently fail to achieve healing. We
      describe a series of 152 consecutive referrals from a nurse-led specialist
      dermatology clinic to a vascular surgical service; a group posing particularly
      challenging problems. This observational study, with median follow-up of 18
      months, describes outcomes in a number of important clinically identifiable
      subgroups. Its findings may assist service planning and discussion of the
      surgical role within multidisciplinary ulcer management.

PMID- 19398421
TI  - Is inflammatory bowel disease a risk factor for early atherosclerosis?
AB  - OBJECTIVES: Chronic inflammatory diseases are associated with an accelerated
      atherosclerotic process. Recent studies have discussed whether inflammatory bowel
      diseases (IBDs) can predict early atherosclerosis. We investigated this
      possibility. METHODS: The study consisted of IBD cases (group 1, n = 40) and
      healthy persons (group 2, n = 40). The IBD group was selected so as not to have
      vascular disease or the presence of established major cardiovascular risk
      factors. RESULTS: Group 1 cases showed a significant increase in carotid intima
      media thickness (cIMT; P = .01). Carotid artery stiffness was impaired in group 1
      (P = .03) and high-sensitivity C-reactive protein (hsCRP), homeostasis model
      assessment of insulin resistance (HOMA-IR), and homocysteine (Hyc) were higher in
      group 1 patients (P = .02, P = .03, P = .05). CONCLUSIONS: Inflammatory bowel
      disease patients have an increased risk of early atherosclerosis as shown by
      greater values of cIMT, carotid artery stiffness, Hyc, hsCRP, and insulin
      resistance.

PMID- 19398422
TI  - Do not forget the distal lower limb veins in screening patients with spinal cord
      injuries for deep venous thromboses.
AB  - In this prospective study, we aimed to document the rate and localization of deep
      venous thromboses in patients with spinal cord injuries. Patients with paraplegia
      or tetraplegia were screened by a serial color duplex sonography protocol for
      deep venous thrombosis within the first 36 hours after admission, at day 7, and
      at day 21. Sonography was performed by a complete scan including the veins below
      the knee. A total of 139 patients were included (19-90 years, 63.5% male).
      Cumulative rate of deep venous thrombosis after 3 duplex scans was 45.3% (n =
      63). In 71.4% (n = 45), thromboses were localized below the knee. Because of the
      relevant number of distal vein thromboses, inclusion of the calf veins during
      screening scans is suggested. Further studies are needed to analyze the clinical
      benefit of diagnosing and treating distal vein thromboses.

PMID- 19398423
TI  - Consequence and factors related to not offering reperfusion therapy in STEMI.
AB  - INTRODUCTION: Varied reasons existed for not offering reperfusion therapy in ST
      elevation myocardial infarction and results in poor outcomes, and if related
      factors could be delineated, corrective measures can be attempted. METHOD: We
      compared variables between participants not receiving reperfusion therapy and
      those receiving single reperfusion therapy. Multivariate analysis examined the
      contribution of non-reperfusion therapy to death and factors related to it.
      RESULTS: Non-reperfusion therapy was older and had a lower frequency of typical
      chest pain, but more dyspnea, and post cardiac resuscitation. They had more heart
      failure and death. Non-reperfusion therapy was an independent factor related to
      cardiac death, and factors related to non-reperfusion therapy were age, type of
      hospital, presenting features on admission (dyspnea and post cardiac
      resuscitation), lack of typical chest pain, and not being referred to.
      CONCLUSION: Non-reperfusion therapy had 2 to 3 times higher in-hospital
      mortality. Factors related to not offering reperfusion therapy, aside from age,
      appeared to be amendable to better management.

PMID- 19398424
TI  - Prevalence of overweight, obesity, and metabolic syndrome among adult Kuwaitis:
      results from community-based national survey.
AB  - BACKGROUND: Although, metabolic syndrome and obesity are cardiovascular risk
      factors, little systematically collected community-based data are available from
      the Arabian Gulf region. METHODS: We report a nationwide cross-sectional study
      from Kuwait. A random sample was selected. Demographic and clinical data were
      collected. Blood tests including fasting blood glucose, high-density lipoprotein
      cholesterol, and triglycerides were collected. Metabolic syndrome was defined
      according to International Diabetes Federation criteria. Overweight and obesity
      were defined as body mass index >or=25, and body mass index >or=30, respectively.
      RESULTS: Prevalence of overweight, obesity, and metabolic syndrome in adult
      Kuwaiti population were 80.4%, 47.5%, and 36.2%, respectively. Overweight and
      obesity rates were higher in women 81.9% and 53% compared to men 78% and 39.2%,
      respectively (P = .02, P > .001). MetS was equally distributed between men and
      women at 36.2% and 36.1%. CONCLUSIONS: Prevalence of overweight, obesity, and
      metabolic syndrome is alarmingly high in Kuwait. This requires urgent and active
      community-based public health intervention.

PMID- 19398425
TI  - Evidence for telomerase activation in VSMCs exposed to hyperglycemic and
      hyperhomocysteinemic conditions.
AB  - PURPOSE: While diabetes and homocysteinemia have been demonstrated to be
      independent risk factors for progression of vascular disease, the activation of
      telomerase has not been linked to the potent effects of high levels of
      homocysteine (Hcy) and glucose on vascular smooth muscle cells (VSMC). We
      examined the proliferative response of VSMCs, resulting from hyperglycemia and
      hyperhomocysteinemia and their effects on telomerase activity. METHODS: Primary
      cultures of VSMC from human aorta and arteries were used in this experiment from
      3rd -5th passages. Hcy or/and glucose were added to the cell culture media in
      doses equivalent to plasma levels of Hcy in patients with moderate, high
      homocysteinemia, or physiologically high concentrations of glucose as seen in
      diabetics. The modified telomeric repeat amplification protocol was used for
      telomerase activity assay. Cytotoxicity, viability, proliferation, protein
      phosphorylation, were determined in cultures treated and not treated with Hcy and
      glucose. RESULTS: The mitogenic effect of Hcy and glucose on VSMC, independently
      and together, was observed at 48 hours after treatment. The viable cell numbers
      were significantly increased at doses comparable to plasma levels of Hcy in
      hyperhomocysteinemia, as compared to untreated cultures (p < 0.01). Cells exposed
      to high levels of glucose also exhibited an increased proliferation response (p =
      0.01). Telomerase activity was detected in all sets of VSMC cultures exposed to
      high levels of glucose or/and Hcy (p < 0.01). However, a significant difference
      was not observed in telomerase activity, when high Hcy or high glucose was used
      alone or in concert. Significant dual phosphorylation of p38 MAPK was observed in
      treated cultures but it did not correlate with the telomerase activity detected.
      CONCLUSION: These data establish a link with telomerase activation and the
      mitogenic effect of hyperhomocysteinemia and hyperglycemia.

PMID- 19398426
TI  - Determination of prooxidant--antioxidant balance after acute coronary syndrome
      using a rapid assay: a pilot study.
AB  - The purpose of the current study was to investigate a novel measure of oxidative
      stress in patients with acute coronary syndrome (ACS) using a pro-oxidant
      antioxidant balance (PAB) assay, which is simple and rapid. Blood samples were
      taken from 94 patients admitted with ACS. Pro-oxidant-antioxidant balance values
      were determined in the first and second 12 hours after the onset of symptoms and
      compared with values for 81 age- and sex-matched controls. The mean PAB values in
      the first and second 12-hour samples of patients were both significantly higher
      than that of controls (P < .001). Among patients, PAB values were also
      significantly higher in the second samples compared with the first samples (P <
      .001). These findings indicate a heightened state of oxidative stress following
      ACS and suggest that the PAB value may be considered as a cardiovascular risk
      predictor to estimate the extent of oxidative stress.

PMID- 19398427
TI  - Platelet function following acute cerebral ischemia.
AB  - BACKGROUND: Studies have previously identified increased levels of platelet
      activation following acute ischemic stroke. In order to evaluate new antiplatelet
      agents and their combinations, there is a need for accurate measures of platelet
      activation. METHODS: Blood was taken from 17 patients within 24 hours of an acute
      ischemic stroke, and then at 3, 7, 14 and 42 days. For comparison, a group of 18
      stable arteriopaths had identical tests performed. Platelet aggregation was
      measured using a free platelet counting technique, and platelet surface P
      selectin and monocyte platelet aggregates (MPAs) were measured using flow
      cytometry. Soluble P-selectin and D-dimers were measured by an enzyme linked
      immune assay. RESULTS: The initial level of MPAs was significantly raised in the
      stroke patients compared with the stable patients (p = 0.04, 14.2% vs. 9.3%);
      however, this difference was not significantly higher than later study points
      (14.2%, 10.1%, 9.3%, 11.9%, 11.3%; days 1, 3, 7, 14 and 42 respectively. Day 1
      vs. day 7 p = 0.07 ANOVA). No changes in P-selectin or platelet aggregation were
      identified. D-dimer levels were significantly higher on day 7 than day 42 (p <
      0.01), and fibrinogen levels were elevated on both days 3 and 14 compared with
      day 42. Fibrinogen levels were not elevated compared with stable patients.
      CONCLUSIONS: MPA levels are elevated following an acute ischemic stroke compared
      to stable patients, but no significant change was seen with other platelet
      markers. This study suggests MPAs are a more sensitive marker of platelet
      activation than either P-selectin or aggregation.

PMID- 19398428
TI  - Evaluation of point-of-care activated partial thromboplastin time testing by
      comparison to laboratory-based assay for control of intravenous heparin.
AB  - INTRODUCTION: Patients on intravenous heparin require regular activated partial
      thromboplastin time monitoring. Laboratory-based activated partial thromboplastin
      time assays necessitate a delay between blood sampling and dose adjustment. Point
      of-care testing could permit immediate dose adjustments, potentially enabling
      tighter control of anticoagulation. AIM: To assess equivalence of activated
      partial thromboplastin time measured by conventional laboratory assay and by a
      novel proprietary point-of-care testing system (Hemochron Response, ITC, Thoratec
      Corporation, Edison, NJ) among surgical ward patients on intravenous heparin.
      METHODS: A total of 39 blood samples from patients on intravenous heparin were
      tested with both laboratory and point-of-care assays. Assay equivalence was
      assessed by Bland-Altman analysis. Results. Point-of-care measurements exceeded
      laboratory activated partial thromboplastin time by a mean of 15 seconds
      (standard deviation 19). In 19 cases (49%), the point-of-care measurement would
      have resulted in different heparin dosing from the laboratory activated partial
      thromboplastin time. CONCLUSIONS: The Hemochron Response system is not
      sufficiently accurate for routine ward use compared with laboratory activated
      partial thromboplastin time assays.

PMID- 19398429
TI  - CVTree update: a newly designed phylogenetic study platform using composition
      vectors and whole genomes.
AB  - The CVTree web server (http://tlife.fudan.edu.cn/cvtree) presented here is a new
      implementation of the whole genome-based, alignment-free composition vector (CV)
      method for phylogenetic analysis. It is more efficient and user-friendly than the
      previously published version in the 2004 web server issue of Nucleic Acids
      Research. The development of whole genome-based alignment-free CV method has
      provided an independent verification to the traditional phylogenetic analysis
      based on a single gene or a few genes. This new implementation attempts to meet
      the challenge of ever increasing amount of genome data and includes in its
      database more than 850 prokaryotic genomes which will be updated monthly from
      NCBI, and more than 80 fungal genomes collected manually from several sequencing
      centers. This new CVTree web server provides a faster and stable research
      platform. Users can upload their own sequences to find their phylogenetic
      position among genomes selected from the server's; inbuilt database. All sequence
      data used in a session may be downloaded as a compressed file. In addition to
      standard phylogenetic trees, users can also choose to output trees whose
      monophyletic branches are collapsed to various taxonomic levels. This feature is
      particularly useful for comparing phylogeny with taxonomy when dealing with
      thousands of genomes.

PMID- 19398430
TI  - SITEHOUND-web: a server for ligand binding site identification in protein
      structures.
AB  - SITEHOUND-web (http://sitehound.sanchezlab.org) is a binding-site identification
      server powered by the SITEHOUND program. Given a protein structure in PDB format
      SITEHOUND-web will identify regions of the protein characterized by favorable
      interactions with a probe molecule. These regions correspond to putative ligand
      binding sites. Depending on the probe used in the calculation, sites with
      preference for different ligands will be identified. Currently, a carbon probe
      for identification of binding sites for drug-like molecules, and a phosphate
      probe for phosphorylated ligands (ATP, phoshopeptides, etc.) have been
      implemented. SITEHOUND-web will display the results in HTML pages including an
      interactive 3D representation of the protein structure and the putative sites
      using the Jmol java applet. Various downloadable data files are also provided for
      offline data analysis.

PMID- 19398431
TI  - Should we aspire to screen preschool children for conduct disorder?
AB  - Life-course persistent conduct disorder is a major public health problem with
      implications for individual health and for society at large. Recent evidence has
      shown that treatment can be cost-effective, and early symptom detection is
      improving. We weigh the evidence for and against the introduction of population
      screening for conduct disorder in early childhood using Wilson and Jungner's
      criteria.

PMID- 19398432
TI  - Ian Prior and epidemiology in New Zealand.
AB  - Ian Prior was born in Masterton, New Zealand, in 1923, and died in Wellington,
      New Zealand, in 2009. In 1959 Ian became the Director of the Medical Unit at
      Wellington Hospital, and in the early 1960s he established the Epidemiology Unit.
      Without doubt he is the founder of epidemiology in New Zealand, and has also had
      a major influence in Australia and further afield. I was delighted to be invited
      to write this piece about Ian for the Journal of Epidemiology and Community
      Health, not as an obituary but as an essay on an epidemiologist who inspired many
      of us in New Zealand, and whose example will continue to inspire many around the
      world. Ian Prior's work represents not only an important historical legacy but
      also an important guide to the future of epidemiology. This includes his work on
      the effects of social and environmental changes and the wider social context on
      individual "lifestyle", his willingness to work collaboratively with researchers
      from other disciplines including social scientists, his insistence on seeing
      quantitative biomedical phenomena (such as blood pressure) in the wider social
      context, and perhaps most of all his insistence that epidemiologists cannot hide
      from the wider realities of the world in which they live.

PMID- 19398433
TI  - The highs and lows of opportunistic Chlamydia testing: uptake and detection in
      Waikato, New Zealand.
AB  - OBJECTIVE: The uptake rate of Chlamydia trachomatis (Chlamydia) testing among
      young New Zealanders is unknown. The aim was to ascertain age-group Chlamydia
      testing and detection rates within the Waikato area. METHODS: A retrospective
      study was undertaken of all Chlamydia tests within Waikato District Health Board
      during February to October 2008. Non-genital samples and duplicates for any
      individual were excluded. New Zealand 2006 census population data served as
      denominator data. RESULTS: There were 21 104 Chlamydia tests carried out on
      Waikato residents during February to October 2008; of these, 10 847 (51.4%) tests
      were from 15-24-year-olds, and 82.3% were female. Based on tests, uptake among 15
      24-year-olds was 22.2%, 36.9% among females and 7.7% among males, compared with
      9.3% among 25-44-year-olds. Based on individuals, uptake among 15-24-year-olds
      was 17.4%: 28.4% for females and 6.7% for males, with similar rates for Maori
      (13.5%) and non-Maori (15%). Overall 15.8% of tests from 15-24-year-olds were
      positive, 14.4% in females and 23.0% in males (p<0.001), with positivity double
      among Maori (24.2% vs 12.5%; p<0.001). CONCLUSIONS: High rates of Chlamydia
      testing and uptake, particularly among local 15-24-year-old women, may explain
      the high Chlamydia surveillance rates in the Waikato district. While a high
      testing rate among young women is encouraging, lower testing among men is
      notable. This better understanding of existing Waikato testing and detection
      patterns helps prioritise local efforts during planned implementation of
      Chlamydia primary care guidelines, particularly around targeting testing,
      optimising case management and emphasising effective partner notification.

PMID- 19398434
TI  - Pitfalls of internet-accessible diagnostic tests: inadequate performance of a CE
      marked Chlamydia test for home use.
AB  - OBJECTIVES: To evaluate the performance of a Conformitee Europeenne (CE)-marked
      home test for Chlamydia trachomatis (CT) that is available over the internet.
      METHODS: A total of 231 eligible women attending the Social Hygiene Clinic (SHC)
      or Obstetrics-Gynecology (OB-GYN) Clinic in Iloilo City, Philippines were
      recruited to an evaluation of the HandiLab-C Chlamydia home test (HandiLab-C).
      One vaginal swab was tested with HandiLab-C on-site and the second in Cambridge,
      UK with two nucleic acid amplification tests (NAAT), the Roche Amplicor and
      Abbott m2000. The organism load of NAAT-positive swabs was quantified. RESULTS:
      Concordance between the NAATs was high (kappa agreement: 0.984). Using the Abbott
      assay as the gold standard, the sensitivity and specificity of the Roche assay
      were 97.4% and 100%, respectively. CT prevalence by Abbott was 8.0% (8/100) in
      the OB-GYN Clinic and 23.7% (31/131) at SHC. The sensitivity of HandiLab-C was
      12.5% (1/8) and 19.4% (6/31) in OB-GYN and SHC respectively, with specificities
      of 93.5% (86/92) and 88% (88/100) respectively. Overall positive and negative
      predictive values of HandiLab-C were 28% and 84.5% respectively. No correlation
      between HandiLab-C performance and organism load (range: 1.3 x 10(2) to 1.4 x
      10(7) bacteria/swab) was observed. CONCLUSIONS: The performance of HandiLab-C is
      very poor, with the test yielding more false-positive (18/193) than true-positive
      (7/38) results. It remains accessible via the internet under various brand names
      and has retained its CE mark. This situation raises serious concerns about the
      regulation of diagnostic products available via the internet and the standards of
      certain Notified Bodies that issue the CE mark.

PMID- 19398435
TI  - Aspirin resistance testing not ready for "prime time".

PMID- 19398436
TI  - Strain rate evaluation of phasic atrial function in hypertension.
AB  - BACKGROUND: Strain (SI) and strain rate (SR) measure regional myocardial
      deformation and may be a new technique to assess phasic atrial function.
      OBJECTIVE: To examine the feasibility of using SI and SR to evaluate phasic
      atrial function in patients with mild hypertension (HT). PATIENTS AND METHODS:
      The study group comprised 54 patients with mild essential HT (29 women) and 80
      age-matched normal controls (47 women). Standard two-dimensional and Doppler
      echocardiography was performed as well as Doppler tissue imaging. The following
      left atrial (LA) volumes were measured: (a) maximal LA volume or Vol(max); (b)
      minimal LA volume or Vol(min); (c) just before the "p" wave on ECG (Vol(p)).
      Phasic LA volumes were also calculated. Systolic (S-Sr), early diastolic (E-Sr),
      late diastolic (A-Sr) strain rate and SI were measured. RESULTS: Despite no
      differences in indexed maximal LA volume with only mild increases in left
      ventricular mass in the HT cohort compared with normal subjects (mean (SD) 86
      (18) g/m(2) vs 67 (14) g/m(2); p = 0.001), E-Sr was significantly lower in the HT
      cohort. There was a corresponding reduction in indexed conduit volume in the HT
      cohort compared with normal subjects (10.5 (7.5) ml/m(2) vs 13.8 (6.1) ml/m(2); p
      = 0.006). Global E-Sr showed modest negative correlations with LA Vol(max) and LA
      ejection fraction. No significant difference was present in S-Sr, A-Sr or global
      atrial strain between the normal and HT cohorts. CONCLUSION: Mild HT results in a
      reduction in LA conduit volume, although maximal LA volume is unchanged. This is
      reflected by a reduction in E-Sr with preserved S-Sr and A-Sr.

PMID- 19398437
TI  - Aspirin "resistance" and its impact on cardiovascular morbidity and mortality: it
      is real, clinically relevant and should be measured.

PMID- 19398438
TI  - Cardiologists and abdominal obesity: lost in translation?

PMID- 19398439
TI  - A new animal model of postsurgical bowel inflammation and fibrosis: the effect of
      commensal microflora.
AB  - OBJECTIVE: Ileocaecal resection (ICR) is common in Crohn's disease. Inflammation
      and fibrosis frequently recur at the site of anastomosis or in the small
      intestine (SI). No animal models of postsurgical inflammation and fibrosis exist.
      A model of ICR was developed in interleukin 10 (IL10) null and wild-type (WT)
      mice to test the hypothesis that ICR promotes postsurgical inflammation and
      fibrosis in the SI or anastomosis of genetically susceptible IL10 null, but not
      WT or germ-free (GF)-IL10 null mice. METHODS: GF-IL10 null mice were
      conventionalised (CONV) and 3 weeks later randomised to ICR, transection (T) or
      no treatment (NoTx). Age-matched conventionally raised (CONV) WT and GF-IL10 null
      mice received ICR, T or NoTx. Animals were killed 28 days later. Histological
      scoring, real-time PCR for tumour necrosis factor alpha and collagen, and
      immunostaining for CD3(+) T cells assessed inflammation and fibrosis. RESULTS:
      After ICR, CONV-IL10 null, but not CONV-WT mice, developed significant
      inflammation and fibrosis in the SI and inflammation in anastomosis compared with
      NoTx or T controls. Fibrosis occurred in the anastomosis of both CONV-IL10 null
      and CONV-WT mice following ICR. GF-IL10 null mice developed little or no
      inflammation or fibrosis in the SI or anastomosis after ICR. CONCLUSIONS: ICR in
      CONV-IL10 null mice provides a new animal model of postsurgical inflammation and
      fibrosis in the SI and anastomosis. Absence of inflammation and fibrosis in the
      SI of CONV-WT and GF-IL10 null mice following ICR indicates that postsurgical
      small bowel disease occurs only in genetically susceptible IL10 null mice and is
      bacteria dependent.

PMID- 19398440
TI  - Standard steroid treatment for autoimmune pancreatitis.
AB  - OBJECTIVE: To establish an appropriate steroid treatment regimen for autoimmune
      pancreatitis (AIP). METHODS: A retrospective survey of AIP treatment was
      conducted in 17 centres in Japan. The main outcome measures were rate of
      remission and relapse. RESULTS: Of 563 patients with AIP, 459 (82%) received
      steroid treatment. The remission rate of steroid-treated AIP was 98%, which was
      significantly higher than that of patients without steroid treatment (74%,
      77/104; p<0.001). Steroid treatment was given for obstructive jaundice (60%),
      abdominal pain (11%), associated extrapancreatic lesions except the biliary duct
      (11%), and diffuse enlargement of the pancreas (10%). There was no relationship
      between the period necessary to achieve remission and the initial dose (30 mg/day
      vs 40 mg/day) of prednisolone. Maintenance steroid treatment was given in 377
      (82%) of 459 steroid-treated patients, and steroid treatment was stopped in 104
      patients. The relapse rate of patients with AIP on maintenance treatment was 23%
      (63/273), which was significantly lower than that of patients who stopped
      maintenance treatment (34%, 35/104; p = 0.048). From the start of steroid
      treatment, 56% (55/99) relapsed within 1 year and 92% (91/99) relapsed within 3
      years. Of the 89 relapsed patients, 83 (93%) received steroid re-treatment, and
      steroid re-treatment was effective in 97% of them. CONCLUSIONS: The major
      indication for steroid treatment in AIP is the presence of symptoms. An initial
      prednisolone dose of 0.6 mg/kg/day, is recommend, which is then reduced to a
      maintenance dose over a period of 3-6 months. Maintenance treatment with low-dose
      steroid reduces but dose not eliminate relapses.

PMID- 19398441
TI  - Polymorphisms in E-cadherin (CDH1) result in a mis-localised cytoplasmic protein
      that is associated with Crohn's disease.
AB  - BACKGROUND: Patients with Crohn's disease have defects in intestinal epithelial
      permeability that are inadequately explained by known inflammatory bowel disease
      (IBD) susceptibility genes. E-cadherin (CDH1) plays a vital role in maintaining
      the integrity of the intestinal barrier and its cellular localisation is
      disrupted in patients with Crohn's disease. AIM: To determine if polymorphisms in
      the CDH1 gene are associated with Crohn's disease and to determine the function
      associated with these polymorphisms. METHODS: The hypothesis was tested using a
      candidate gene approach using 20 Tag SNPs derived from the HapMap and Crohn's
      disease trios. Functional studies were carried out using HapMap cell lines and
      polarised epithelial cell lines (MDCK-1 and Caco2). RESULTS: Here we show that
      CDH1 is associated with Crohn's disease in 327 trios (rs10431923 excess
      transmission of "TT" genotype; p = 0.0020) and is replicated in the Wellcome
      Trust Case Control Consortium CD data set (TT risk allele; OR 1.2, p = 0.005).
      Patients with the Crohn's disease risk haplotype (rs12597188, rs10431923 and
      rs9935563; GTC allelic frequency 21%; p = 0.000016) exhibited increased E
      cadherin cytoplasmic accumulation in their intestinal epithelium which may be
      explained by the presence of a novel truncated form of E-cadherin. Accordingly,
      expression of this truncated E-cadherin in cultured polarised epithelial cells
      resulted in abnormal intracellular accumulation and impaired plasma membrane
      localisation of both E-cadherin and beta-catenin. CONCLUSION: The mis
      localisation of E-cadherin and beta-catenin may explain the increased
      permeability seen in some patients with Crohn's disease. Thus, the polymorphisms
      identified in CDH1 are important for understanding the pathogenesis of Crohn's
      disease and point to a defect in barrier defence.

PMID- 19398442
TI  - Collagen type III alpha I is a gastro-oesophageal reflux disease susceptibility
      gene and a male risk factor for hiatus hernia.
AB  - BACKGROUND AND OBJECTIVES: Gastro-oesophageal reflux disease (GORD) is a common
      gastrointestinal disorder with a genetic component. Our aim was to identify
      genetic factors associated with GORD. PATIENTS AND METHODS: Four separate patient
      cohorts were analysed using a step-wise approach. (1) Whole genome linkage
      analysis was performed in 36 families. (2) Candidate genes were tested for GORD
      association in a trio cohort. (3) Genetic association was replicated in a case
      control cohort. We also investigated genetic association to hiatus hernia (HH).
      (4) Protein expression was analysed in oesophageal biopsies. RESULTS: A region on
      chromosome 2, containing collagen type III alpha 1 (COL3A1), was identified (LOD
      = 3.3) in families with dominant transmission of GORD, stratified for hiatus
      hernia (HH). COL3A1 showed significant association with GORD in an independent
      paediatric trio cohort (p(corr) = 0.003). The association was male specific
      (p(corr) = 0.018). The COL3A1 association was replicated in an independent adult
      case control cohort (p(corr) = 0.022). Moreover, male specific association to HH
      (p(corr) = 0.019) was found for a SNP not associated to GORD. Collagen type III
      protein was more abundant in oesophageal biopsies from male patients with GORD (p
      = 0.03). CONCLUSION: COL3A1 is a disease-associated gene in both paediatric and
      adult GORD. Furthermore, we show that COL3A1 is genetically associated with HH in
      adult males. The GORD- and HH-associated alleles are different, indicating two
      separate mechanisms leading to disease. Our data provides new insight into GORD
      aetiology, identifying a connective tissue component and indicating a tissue
      remodelling mechanism in GORD. Our results implicate gender differences in the
      genetic risk for both for GORD and HH.

PMID- 19398443
TI  - Activation of a membrane-bound serine protease matriptase on the cell surface.
AB  - Matriptase is a type II transmembrane serine protease. The activation (i.e.
      conversion of the single-chain pro-form to the disulphide-linked-two-chain active
      form) of this enzyme is known to occur via a mechanism requiring its catalytic
      triad. We reported previously that the activated enzyme was produced in the
      conditioned medium when full-length rat matriptase was expressed in monkey kidney
      COS-1 cells. The present study aimed to address when and where the matriptase
      activation occurs. COS-1 cells expressing matriptase were labelled with a
      membrane-impermeable biotin derivative and then solubilized with Triton. Both
      activated and non-activated matriptase molecules were detected in the avidin
      precipitants of Triton extracts, whereas only the non-activated molecules were
      detected in the flow-through fraction of avidin-precipitation procedure. Single
      chain matriptase has been thought to have an inherent activity. Indeed, a
      secreted single-chain variant of recombinant matriptase bearing mutation at the
      activation-cleavage site was found to exhibit the activity in hydrolyzing a
      synthetic peptide substrate at pH 7.5. However, the variant had little activity
      at pH 5.5, as found in the lumen of post-Golgi secretory vesicles. Altogether, it
      is concluded that the activation of matriptase may occur when the enzyme reaches
      the cell surface.

PMID- 19398444
TI  - Lead toxicity, vulnerable subpopulations and emergency preparedness.
AB  - This paper reviews some evidence of the toxic effects of lead (Pb) in the context
      of vulnerable subpopulations and emergency preparedness. Pb is ubiquitous in the
      environment and is used in many building materials. Environmental Pb
      concentrations and body burdens of Pb have been shown to increase following
      disasters. Pb is a systemic toxicant with no known beneficial biological function
      and, for several endpoints, no identified threshold of toxicity. The fetus,
      children, pregnant and elderly are particularly susceptible to some of the toxic
      effects of Pb. Pb exposures in infancy have been shown in vivo to produce an
      equal degree of neurobehavioural impairment as exposures of much longer duration
      at equivalent doses during adolescence. Evidence from animal bioassays indicates
      that the carcinogenic potency of perinatal Pb exposure may be about 3-fold higher
      than adult lifetime exposure at an equivalent dose. Animal assays show up to a 12
      fold difference between fetal, neonatal and adult life stages in sensitivity to
      the immunological effects of Pb. Pb exposure is associated with increased risk of
      cardiovascular and cerebrovascular morbidity and mortality--health endpoints for
      which the elderly are at increased risk. Finally, endogenous and exogenous
      variables, such as psychological and physiological stress, dietary deficiencies
      and concomitant exposure to other chemical, biological and radiological hazards,
      can also potentially modify or potentiate the toxic effects of Pb. Because of the
      potential for concurrent influence of these modifying variables in a post
      disaster environment, emergency response planners are encouraged to consider
      disaster victims and responders, as a whole, as a potentially vulnerable
      subpopulation.

PMID- 19398445
TI  - Taxonomic turmoil down-under: recent developments in Australian orchid
      systematics.
AB  - BACKGROUND: The issue of determining the most appropriate rank for each accepted
      taxon fuels ongoing controversy throughout systematics. The particularly marked
      escalation of such issues in modern Australian orchid systematics merits
      examination, not only because of wider implications in taxonomy but also because
      of direct effects on studies of comparative biology and conservation management.
      SCOPE: This paper briefly reviews the causes of recent taxonomic turmoil for
      Australian orchids and outlines new research opportunities and conservation
      implications arising from an improved understanding of their molecular
      phylogenetics. CONCLUSIONS: DNA sequencing and intensified field work have
      contributed towards a much improved understanding of Australian orchid
      systematics. Great progress has been made in discerning monophyletic groups or
      clades. Fresh interpretations of morphological evolution have been made possible
      by comparisons with the results of DNA analyses. Significant conceptual shifts
      from polymorphic species concepts to biological and phylogenetic concepts have
      also elevated the discovery and description of new species. Consequently, over
      the past decade, the number of Australian orchid species recognized by
      taxonomists has risen from approx. 900 to 1200. Similarly, the number of genera
      recognized by some taxonomists has increased from 110 to 192, resulting in 45% of
      Australian species/subspecies being assigned a new generic epithet since 2000. At
      higher taxonomic levels, much of the recent controversy in Australian orchid
      systematics reflects a divergence in views about where to split and assign formal
      names within unequivocally monophyletic groups. Differences regarding
      typification in the case of Caladenia have added additional confusion and
      complexity. However, new insights into and research opportunities concerning
      speciation processes in orchids have arisen from the wealth of new data and
      discrimination of species. Robustly supported molecular analyses of most clades
      enable comparative biological studies of Australian orchids to be conducted as
      never before. Outstanding subjects exist for exploring pollination by sexual
      deception and understanding the intricacies of mycorrhizal relationships and
      orchid conservation biology.

PMID- 19398446
TI  - Trapline foraging by pollinators: its ontogeny, economics and possible
      consequences for plants.
AB  - BACKGROUND: Trapline foraging (repeated sequential visits to a series of feeding
      locations) has been often observed in pollinators collecting nectar or pollen
      from flowers. Although field studies on bumble-bees and hummingbirds have
      clarified fundamental aspects of this behaviour, trapline foraging still poses
      several difficult questions from the perspectives of both animals and plants.
      These questions include whether and how traplining improves foraging performance,
      how animals develop traplines with accumulating foraging experience, and how
      traplining affects pollen flow or plant reproduction. SCOPE: First, we review our
      previous work performed by using computer simulations and indoor flight-cage
      experiments with bumble-bees foraging from arrays of automated feeders. Our
      findings include the following: (1) traplining benefits foragers that are
      competing for resources that replenish in a decelerating way, (2) traplining is a
      learned behaviour that develops over a period of hours and (3) the establishment
      of traplines could be hampered by spatial configuration of plants such as
      zigzags. Second, using a simulation model linking pollinator movement and pollen
      transfer, we consider how service by pollinators with different foraging patterns
      (searchers or trapliners) would affect pollen flow. Traplining increases mating
      distance and mate diversity, and reduces 'iterogamy' (self-pollination caused by
      return visits) at the population level. Furthermore, increased visitation rates
      can have opposite effects on the reproductive success of a plant, depending on
      whether the visitors are traplining or searching. Finally, we discuss possible
      consequences of traplining for plants in the light of new experimental work and
      modelling. CONCLUSIONS: We suggest that trapline foraging by pollinators
      increases variation among plant populations in genetic diversity, inbreeding
      depression and contributions of floral traits to plant fitness, which should in
      turn affect the rates and directions of floral evolution. More theoretical and
      empirical studies are needed to clarify possible outcomes of such a neglected
      side of pollination.

PMID- 19398447
TI  - GeneRegionScan: a Bioconductor package for probe-level analysis of specific,
      small regions of the genome.
AB  - SUMMARY: Whole-genome microarrays allow us to interrogate the entire
      transcriptome of a cell. Affymetrix microarrays are constructed using several
      probes that match to different regions of a gene and a summarization step reduces
      this complexity into a single value, representing the expression level of the
      gene or the expression level of an exon in the case of exon arrays. However, this
      simplification eliminates information that might be useful when focusing on
      specific genes of interest. To address these limitations, we present a software
      package for the R platform that allows detailed analysis of expression at the
      probe level. The package matches the probe sequences against a target gene
      sequence (either mRNA or DNA) and shows the expression levels of each probe along
      the gene. It also features functions to fit a linear regression based on several
      genetic models that enables study of the relationship between gene expression and
      genotype. AVAILABILITY AND IMPLEMENTATION: The software is implemented as a
      platform-independent R package available through the Bioconductor repository at
      http://www.bioconductor.org/. It is licensed as GPL 2.0. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 19398448
TI  - VARNA: Interactive drawing and editing of the RNA secondary structure.
AB  - DESCRIPTION: VARNA is a tool for the automated drawing, visualization and
      annotation of the secondary structure of RNA, designed as a companion software
      for web servers and databases. FEATURES: VARNA implements four drawing
      algorithms, supports input/output using the classic formats dbn, ct, bpseq and
      RNAML and exports the drawing as five picture formats, either pixel-based (JPEG,
      PNG) or vector-based (SVG, EPS and XFIG). It also allows manual modification and
      structural annotation of the resulting drawing using either an interactive point
      and click approach, within a web server or through command-line arguments.
      AVAILABILITY: VARNA is a free software, released under the terms of the GPLv3.0
      license and available at http://varna.lri.fr. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 19398449
TI  - Optimizing static thermodynamic models of transcriptional regulation.
AB  - MOTIVATION: Modeling transcriptional regulation using thermo-dynamic modeling
      approaches has become increasingly relevant as a way to gain a detailed
      understanding of transcriptional regulation. Thermodynamic models are able to
      model the interactions between transcription factors (TFs) and DNA that lead to a
      specific transcriptional output of the target gene. Such models can be 'trained'
      by fitting their free parameters to data on the transcription rate of a gene and
      the concentrations of its regulating factors. However, the parameter fitting
      process is computationally very expensive and this limits the number of
      alternative types of model that can be explored. RESULTS: In this study, we
      evaluate the 'optimization landscape' of a class of static, quantitative models
      of regulation and explore the efficiency of a range of optimization methods. We
      evaluate eight optimization methods: two variants of simulated annealing (SA),
      four variants of gradient descent (GD), a hybrid SA/GD algorithm and a genetic
      algorithm. We show that the optimization landscape has numerous local optima,
      resulting in poor performance for the GD methods. SA with a simple geometric
      cooling schedule performs best among all tested methods. In particular, we see no
      advantage to using the more sophisticated 'LAM' cooling schedule. Overall, a good
      approximate solution is achievable in minutes using SA with a simple cooling
      schedule.

PMID- 19398450
TI  - Rahnuma: hypergraph-based tool for metabolic pathway prediction and network
      comparison.
AB  - SUMMARY: We present a tool called Rahnuma for prediction and analysis of
      metabolic pathways and comparison of metabolic networks. Rahnuma represents
      metabolic networks as hypergraphs and computes all possible pathways between two
      or more metabolites. It provides an intuitive way to answer biological ques-
      tions focusing on differences between organisms or the evolution of different
      species by allowing pathway-based metabolic network comparisons at an organism as
      well as at a phylogenetic level. AVAILABILITY: Rahnuma is available online at
      http://portal.stats.ox.ac.uk:8080/rahnuma/.

PMID- 19398451
TI  - penalizedSVM: a R-package for feature selection SVM classification.
AB  - SUMMARY: Support vector machine (SVMs) classification is a widely used and one of
      the most powerful classification techniques. However, a major limitation is that
      SVM cannot perform automatic gene selection. To overcome this restriction, a
      number of penalized feature selection methods have been proposed. In the R
      package 'penalizedSVM' implemented penalization functions L(1) norm and Smoothly
      Clipped Absolute Deviation (SCAD) provide automatic feature selection for SVM
      classification tasks. AVAILABILITY: The R package 'penalizedSVM' is available
      from the Comprehensive R Archive Network (http://cran.r-project.org/) under GPL-2
      or later.

PMID- 19398452
TI  - Orthostatic intolerance and the cardiovascular response to early postoperative
      mobilization.
AB  - BACKGROUND: A key element in enhanced postoperative recovery is early
      mobilization which, however, may be hindered by orthostatic intolerance, that is,
      an inability to sit or stand because of symptoms of cerebral hypoperfusion as
      intolerable dizziness, nausea and vomiting, feeling of heat, or blurred vision.
      We assessed orthostatic tolerance in relation to the postural cardiovascular
      responses before and shortly after open radical prostatectomy. METHODS:
      Orthostatic tolerance and the cardiovascular response to sitting and standing
      were evaluated on the day before surgery and 6 and 22 h after operation in 16
      patients. Non-invasive systolic (SAP) and diastolic arterial pressure (DAP)
      (Finometer), heart rate, cardiac output (CO, Modelflow), total peripheral
      resistance (TPR), and central venous oxygen saturation (Scv(O2)) were monitored.
      RESULTS: Before surgery, no patients had symptoms of orthostatic intolerance. In
      contrast, 8 (50%) and 2 (12%) patients were orthostatic intolerant at 6 and
      approximately 22 h after surgery, respectively. Before surgery, SAP, DAP, and TPR
      increased (P<0.05), whereas CO did not change (P>0.05) and Scv(O2) decreased
      (P<0.05) upon mobilization. At 6 h after operation, SAP and DAP declined with
      mobilization (P<0.05) and the arterial pressure response differed from the
      preoperative response both upon sitting (P<0.05) and standing (P<0.05) due to
      both impaired TPR and CO. At approximately 22 h, the SAP and DAP responses to
      mobilization did not differ from the preoperative evaluation (P>0.05).
      CONCLUSIONS: The early postoperative postural cardiovascular response is impaired
      after radical prostatectomy with a risk of orthostatic intolerance, limiting
      early postoperative mobilization. The pathogenic mechanisms include both impaired
      TPR and CO responses.

PMID- 19398453
TI  - Motivational influences on anaesthetists' use of practice guidelines.
AB  - BACKGROUND: With the proliferation of practice guidelines in anaesthesia comes
      the possibility that anaesthetists may, during the course of their work, commit
      'violations' (actions that are not intended to cause harm to patients, but that
      deviate from guidelines). These may have a long-term impact on patient safety,
      and so there is a need to understand what makes anaesthetists decide to follow or
      deviate from guidelines. METHODS: A questionnaire on the use of guidelines was
      completed by 629 College Fellows. This presented three anaesthetic scenarios,
      each of which involved a deviation from a guideline, and asked respondents to
      rate their beliefs about the likely outcome of the violation, the level of social
      approval they would have for violating, the amount of control they would have
      over violating, and the practice of their peers with regard to violating.
      RESULTS: In all three scenarios, beliefs about the outcome of violating and the
      amount of control over violating predicted respondents' self-reported likelihood
      that they would commit the violation. In two scenarios, beliefs about the
      practice of peers predicted violating. Level of social approval predicted
      violating in one scenario only. CONCLUSIONS: Anaesthetists' decisions to follow
      or deviate from guidelines are influenced by the beliefs they hold about the
      consequences of their actions, the direct or indirect influence of others, and
      the presence of factors that encourage or facilitate particular courses of
      action.

PMID- 19398454
TI  - Real-time ultrasound-guided paramedian epidural access: evaluation of a novel in
      plane technique.
AB  - BACKGROUND: Current methods of locating the epidural space rely on surface
      anatomical landmarks and loss-of-resistance (LOR). We are not aware of any data
      describing real-time ultrasound (US)-guided epidural access in adults. METHODS:
      We evaluated the feasibility of performing real-time US-guided paramedian
      epidural access with the epidural needle inserted in the plane of the US beam in
      15 adults who were undergoing groin or lower limb surgery under an epidural or
      combined spinal-epidural anaesthesia. RESULTS: The epidural space was
      successfully identified in 14 of 15 (93.3%) patients in 1 (1-3) attempt using the
      technique described. There was a failure to locate the epidural space in one
      elderly man. In 8 of 15 (53.3%) patients, studied neuraxial changes, that is,
      anterior displacement of the posterior dura and widening of the posterior
      epidural space, were seen immediately after entry of the Tuohy needle and
      expulsion of the pressurized saline from the LOR syringe into the epidural space
      at the level of needle insertion. Compression of the thecal sac was also seen in
      two of these patients. There were no inadvertent dural punctures or complications
      directly related to the technique described. Anaesthesia adequate for surgery
      developed in all patients after the initial spinal or epidural injection and
      recovery from the epidural or spinal anaesthesia was also uneventful.
      CONCLUSIONS: We have demonstrated the successful use of real-time US guidance in
      combination with LOR to saline for paramedian epidural access with the epidural
      needle inserted in the plane of the US beam.

PMID- 19398455
TI  - Lysostaphin eradicates established Staphylococcus aureus biofilms in jugular vein
      catheterized mice.
AB  - OBJECTIVES: Staphylococcus aureus infections associated with indwelling devices
      can be very difficult to treat due to the recalcitrant nature of bacterial
      biofilms to conventional antibiotics. Lysostaphin has been shown to clear S.
      aureus biofilms in vitro, and in this study we determined whether lysostaphin
      could also eradicate established S. aureus biofilms on implanted jugular vein
      catheters in mice. METHODS: Jugular vein catheterized mice (four to six per
      group) challenged with S. aureus developed multiorgan infection and biofilm
      infections on the catheters. The infected mice with established biofilms received
      various doses of recombinant lysostaphin through the catheters, administered up
      to three times daily for up to 4 days. Some mice also received lysostaphin
      combined with nafcillin. Following treatment, mice were sacrificed and cfu on the
      catheter and in the liver and heart were determined. In another set of
      experiments, implanted jugular vein catheters in mice were pre-instilled with
      lysostaphin to determine whether this pre-treatment would protect the mice from
      biofilm infection. RESULTS AND CONCLUSIONS: Lysostaphin administered at 15 mg/kg
      in combination with 50 mg/kg nafcillin three times per day for 4 days eradicated
      established S. aureus, including methicillin-resistant S. aureus, biofilms from
      implanted catheters and sterilized heart and liver infections of S. aureus
      infected mice. Furthermore, a single pre-instillation of 10 mg/kg lysostaphin in
      catheters completely protected catheterized mice from a subsequent biofilm
      infection. These results demonstrate that lysostaphin is an effective treatment
      as well as prophylaxis for S. aureus biofilms on indwelling catheters.

PMID- 19398456
TI  - Increased prevalence and clonal dissemination of multidrug-resistant Pseudomonas
      aeruginosa with the blaIMP-1 gene cassette in Hiroshima.
AB  - OBJECTIVES: The aim of this study was to evaluate the dissemination of metallo
      beta-lactamase (MBL)-encoding genes among multidrug-resistant (MDR) Pseudomonas
      aeruginosa isolates recovered from major hospitals in the Hiroshima region.
      METHODS: During July to December from 2004 to 2006, a surveillance of eight major
      hospitals in the Hiroshima region identified 387 non-duplicate isolates resistant
      to imipenem (MIC >or= 16 mg/L). They were screened for resistance to amikacin
      (MIC >or= 64 mg/L) and ciprofloxacin (MIC >or= 4 mg/L) and MBL-encoding genes.
      The structure of the variable regions of the integrons was determined using PCR
      mapping. Clonality was assessed using PFGE and multilocus sequence typing (MLST).
      RESULTS: The frequency of MBL-positive isolates in MDR P. aeruginosa isolates
      significantly increased from 42.3% in 2004 to 81.4% in 2006. Most of the MBL
      positive isolates produced IMP-1 followed by VIM-2. The bla(IMP-1) and bla(VIM-2)
      genes were present in class 1 integrons. Characterization of the variable regions
      of the integron showed the presence of six different gene cassette arrays in
      bla(IMP-1) cassettes and a single array in bla(VIM-2) cassettes. The IMP-1
      producers belonged to two clonal lineages using PFGE and MLST analyses and the
      integron variations correlated well with the clonal complexes. Among them,
      strains positive for a newly identified In113-derived bla(IMP-1) gene cassette
      array were most widely distributed in Hiroshima. CONCLUSIONS: This study shows a
      dramatic increase in MBL genes, primarily bla(IMP-1), in MDR P. aeruginosa
      isolates in Hiroshima during these 3 years. In addition, MDR P. aeruginosa with
      the newly discovered In113-derived bla(IMP-1) gene cassette array appears to be
      clonally expanding.

PMID- 19398457
TI  - Antiretroviral drug interactions: often unrecognized, frequently unavoidable,
      sometimes unmanageable.
AB  - Patients with HIV who are receiving antiretroviral (ARV) therapy are at high risk
      for drug-drug interactions (DDIs), which can significantly impact patient care
      and represent a substantial opportunity cost for healthcare systems. DDIs are
      prevalent in the developed world and in resource-poor settings, with the cost
      being potentially greater in the latter. Although practically unavoidable in HIV
      care, many DDIs can be better managed, reducing the risks to patients and the
      burden on resources. The scope for DDI management is likely to be greater in the
      developed world, due to the availability of new agents and second-line drugs,
      which allow greater flexibility of ARV regimens and co-administered drug choice.
      The advent of electronic prescribing and patient medication records represents an
      opportunity to aid the identification and management of DDIs. Searchable
      electronic databases of HIV drug interactions are available, which are a useful
      tool for HIV healthcare professionals and non-specialists for managing DDIs
      involving ARVs. Although general active systems that alert prescribers to DDIs
      currently exist, there is an indication for the development of specialist active
      databases to be incorporated into electronic prescribing or dispensing systems,
      with the aim of improving the quality of prescribing and the safe dispensing of
      the therapeutically risky drugs and complicated regimens used in HIV management.

PMID- 19398458
TI  - Comparative in vitro activities of nemonoxacin, doripenem, tigecycline and 16
      other antimicrobials against Nocardia brasiliensis, Nocardia asteroides and
      unusual Nocardia species.
AB  - OBJECTIVES: The aim of this study was to assess the in vitro activities of
      nemonoxacin (a novel non-fluorinated quinolone), doripenem, tigecycline and 16
      other antimicrobial agents against the Nocardia species. METHODS: MICs of 19
      antimicrobial agents for 125 clinical isolates of the Nocardia species were
      determined by the broth microdilution method. RESULTS: Nocardia brasiliensis (n =
      61), Nocardia asteroides (n = 45), Nocardia flavorosea (n = 5), Nocardia
      otitidiscaviarum (n = 4), Nocardia farcinica (n = 3), Nocardia beijingensis (n =
      2), Nocardia puris (n = 2) and one each of Nocardia nova, Nocardia jinanensis and
      Nocardia takedensis were identified based on a 16S rRNA gene sequencing analysis.
      For N. brasiliensis isolates, the MIC(90)s of the tested quinolones were in the
      order nemonoxacin < gemifloxacin = moxifloxacin < levofloxacin = ciprofloxacin,
      and the MIC(90)s of the tested carbapenems were in the order doripenem =
      meropenem < ertapenem < imipenem. Tigecycline had a lower MIC(90) (1 mg/L) than
      linezolid (8 mg/L). For N. asteroides isolates, the MIC(90)s of the tested
      quinolones were in the order nemonoxacin < gemifloxacin = moxifloxacin <
      levofloxacin < ciprofloxacin, and the MIC(90)s of the tested carbapenems were in
      the order doripenem = meropenem = imipenem < ertapenem. For the other 19 Nocardia
      species isolates, nemonoxacin showed good activity with the lowest MIC(90) of the
      tested quinolones. Among the four tested carbapenems, doripenem and meropenem had
      comparatively lower MIC(90)s. CONCLUSIONS: The results of this in vitro study
      suggest that nemonoxacin, linezolid and tigecycline show promise as treatment
      options for nocardiosis. Further investigation of their clinical role is
      warranted.

PMID- 19398459
TI  - Pharmacokinetics and biodistribution of amphotericin B in rats following oral
      administration in a novel lipid-based formulation.
AB  - OBJECTIVES: To assess the pharmacokinetics and biodistribution of amphotericin B
      (AmB) following oral administration in a novel mono/diglyceride-phospholipid
      formulation and to compare with intravenous (iv) administrations using commercial
      formulations. METHODS: Rats were allocated into the following treatment groups:
      oral gavage of AmB dispersed in mono/diglyceride-phospholipid formulation at
      doses of 4.5 and 10 mg/kg; iv bolus administration of 0.8 mg/kg Fungizone; iv
      bolus of 5 mg/kg Abelcet and iv bolus of 5 mg/kg AmBisome. Blood was sampled from
      jugular vein cannula at certain time points. The animals were sacrificed 72 h
      following administration of AmB and multiple tissues were harvested. The
      concentration of AmB in plasma and tissues was determined by means of HPLC. The
      plasma creatinine concentrations were determined using an enzymatic kit. RESULTS:
      The pharmacokinetics and tissue distribution of AmB following iv administrations
      of the commercial formulations were found to be highly formulation dependent. The
      terminal half-life and biodistribution of orally administered AmB in a
      mono/diglyceride-phospholipid formulation resembled those of Fungizone. The
      larger volume of the co-administered lipid-based formulation in the case of the
      higher dose of orally administered AmB resulted in flip-flop kinetics and in
      preferential distribution into the kidneys. No nephrotoxicity was detected for
      any formulation and route of administration. CONCLUSIONS: Oral administration of
      AmB in a mono/diglyceride-phospholipid formulation to rats resulted in
      significant intestinal absorption into the systemic circulation with
      pharmacokinetic and biodistribution properties similar to a micellar iv
      preparation.

PMID- 19398460
TI  - Meropenem dosing in critically ill patients with sepsis and without renal
      dysfunction: intermittent bolus versus continuous administration? Monte Carlo
      dosing simulations and subcutaneous tissue distribution.
AB  - OBJECTIVES: To compare the plasma and subcutaneous tissue concentration-time
      profiles of meropenem administered by intermittent bolus dosing or continuous
      infusion to critically ill patients with sepsis and without renal dysfunction,
      and to use population pharmacokinetic modelling and Monte Carlo simulations to
      assess the cumulative fraction of response (CFR) against Gram-negative pathogens
      likely to be encountered in critical care units. PATIENTS AND METHODS: We
      randomized 10 patients with sepsis to receive meropenem by intermittent bolus
      administration (n = 5; 1 g 8 hourly) or an equal dose administered by continuous
      infusion (n = 5). Serial subcutaneous tissue concentrations were determined using
      microdialysis and compared with plasma data for first-dose and steady-state
      pharmacokinetics. Population pharmacokinetic modelling of plasma data and Monte
      Carlo simulations were then undertaken with NONMEM. RESULTS: It was found that
      continuous infusion maintains higher median trough concentrations, in both plasma
      (intermittent bolus 0 versus infusion 7 mg/L) and subcutaneous tissue (0 versus 4
      mg/L). All simulated intermittent bolus, extended and continuous infusion dosing
      achieved 100% of pharmacodynamic targets against most Gram-negative pathogens.
      Superior obtainment of pharmacodynamic targets was achieved using administration
      by extended or continuous infusion against less susceptible Pseudomonas
      aeruginosa and Acinetobacter species. CONCLUSIONS: This is the first study to
      compare the relative concentration-time data of bolus and continuous
      administration of meropenem at the subcutaneous tissue and plasma levels. We
      found that the administration of meropenem by continuous infusion maintains
      higher concentrations in subcutaneous tissue and plasma than by intermittent
      bolus dosing. Administration by extended or continuous infusion will achieve
      superior CFR against less-susceptible organisms in patients without renal
      dysfunction.

PMID- 19398461
TI  - Pharmacokinetic variability of antiretroviral drugs and correlation with
      virological outcome: 2 years of experience in routine clinical practice.
AB  - OBJECTIVES: To assess the inter-individual and intra-individual plasma
      concentration variabilities of non-nucleoside reverse transcriptase inhibitors
      (NNRTIs) and protease inhibitors (PIs) in routine clinical practice and to
      investigate their relationships with virological failure. METHODS: We
      retrospectively enrolled HIV-infected patients undergoing therapeutic drug
      monitoring (TDM) of NNRTIs and PIs during routine outpatient visits. Plasma drug
      concentrations were measured by HPLC-UV and were considered therapeutic if above
      the proposed minimum efficacy trough concentration. Inter-individual and intra
      individual variabilities were evaluated through the coefficient of variation
      (CV). RESULTS: A total of 457 PI and 172 NNRTI plasma concentrations were
      measured from 363 patients (HIV-RNA <50 copies/mL in 70.8%, median CD4 count 434
      cells/mm(3)). NNRTIs showed less inter-individual (CV(inter) 54.8% versus 84.3%)
      and intra-individual (CV(intra) 19.0% versus 38.1%) pharmacokinetic variabilities
      than PIs. Intra-individual variability was constantly lower than inter-individual
      variability for each drug. Subtherapeutic drug concentrations were observed in
      106 samples (16.9%). Older age (P = 0.020) and higher viral load (P = 0.013) were
      associated with subtherapeutic levels. Patients with therapeutic levels had a
      viral load of <50 copies/mL more frequently than those with subtherapeutic levels
      (74.8% versus 63.2%, P = 0.020). The estimated proportion with virological
      failure at 24 weeks was 0.21 in patients with suboptimal baseline drug levels and
      0.08 in those with optimal levels (P < 0.001). In the multivariate analysis,
      therapeutic drug levels showed an independent negative association with
      virological failure (P = 0.004). CONCLUSIONS: A wide inter-individual and limited
      intra-individual pharmacokinetic variabilities, together with the demonstration
      of a concentration-response relationship, suggest that TDM is a useful tool for
      the clinical management of patients treated with NNRTIs or PIs.

PMID- 19398462
TI  - KORRIGAN1 and its aspen homolog PttCel9A1 decrease cellulose crystallinity in
      Arabidopsis stems.
AB  - KORRIGAN1 (KOR1) is a membrane-bound cellulase implicated in cellulose
      biosynthesis. PttCel9A1 from hybrid aspen (Populus tremula L. x tremuloides
      Michx.) has high sequence similarity to KOR1 and we demonstrate here that it
      complements kor1-1 mutants, indicating that it is a KOR1 ortholog. We
      investigated the function of PttCel9A1/KOR1 in Arabidopsis secondary growth using
      transgenic lines expressing 35S::PttCel9A1 and the KOR1 mutant line irx2-2. The
      presence of elevated levels of PttCel9A1/KOR1 in secondary walls of
      35S::PttCel9A1 lines was confirmed by in muro visualization of cellulase
      activity. Compared with the wild type, 35S::PttCel9A1 lines had higher
      trifluoroacetic acid (TFA)-hydrolyzable glucan contents, similar Updegraff
      cellulose contents and lower cellulose crystallinity indices, as determined by
      (13)C solid-state nuclear magnetic resonance (NMR) spectroscopy. irx2-2 mutants
      had wild-type TFA-hydrolyzable glucan contents, but reduced Updegraff cellulose
      contents and higher than wild-type cellulose crystallinity indices. The data
      support the hypothesis that PttCel9A1/KOR1 activity is present in cell walls,
      where it facilitates cellulose biosynthesis in a way that increases the amount of
      non-crystalline cellulose.

PMID- 19398464
TI  - The use of computed radiography for routine linear accelerator and simulator
      quality control.
AB  - Computed radiography (CR) systems were originally developed for the purpose of
      clinical imaging, and there has been much work published on its effectiveness as
      a film replacement for this end. However, there has been little published on its
      use for routine linear accelerator and simulator quality control, and therefore
      we have evaluated the use of the Kodak 2000RT system with large Agfa CR plates as
      a replacement for film for this function. A prerequisite for any such use is a
      detailed understanding of the system behaviour, hence characteristics such as
      spatial uniformity of response, reproducibility of spatial accuracy, plate signal
      decay with time and the dose-response of plates were investigated. Finally, a
      comparison of results obtained using CR for the measurement of radiation field
      dimensions was made against those from radiographic film, and found to be in
      agreement within 0.1 mm (mean difference for high-resolution images, 0.3 mm root
      mean square difference) for megavoltage images and 0.3 mm (maximum difference)
      for simulator images. In conclusion, the CR system has been shown to be a good
      alternative to radiographic film for routine quality control of linear
      accelerators and simulators.

PMID- 19398463
TI  - Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a
      randomized, controlled trial.
AB  - OBJECTIVE: To determine if oral clonidine would reduce the duration of opioid
      detoxification for neonatal abstinence syndrome. METHODS: Infants with
      intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2
      consecutive modified Finnegan scores of > or =9) were enrolled at 2 hospitals
      during 2002-2005 and followed until final hospital discharge. All enrolled
      infants (80) received oral diluted tincture of opium according to a standardized
      algorithm and were randomly assigned to receive oral clonidine (1 microg/kg every
      4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of
      opioid therapy. Secondary outcomes included the amount of opium required to
      control symptoms, number of treatment failures, and differences in blood
      pressure, heart rate, and oxygen saturation. RESULTS: The median length of
      therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8-15
      days]) than in the placebo group (15 days [95% confidence interval: 12-17 days]).
      In the clonidine group, 7 infants required restarting opium after initial
      discontinuation versus none in the placebo group, with the total length of
      treatment/observation remaining significantly less in the clonidine group. Higher
      dosages of opium were required by 40% of the infants in the placebo group versus
      20% in the clonidine group. Treatment failures occurred in 12.5% of the infants
      in the placebo group versus none in the clonidine group. Hypertension,
      hypotension, bradycardia, or desaturations did not occur in either group. Three
      infants in the clonidine group died as a result of myocarditis, sudden infant
      death syndrome, and homicide, all after hospital discharge and before 6 months of
      age. CONCLUSIONS: In this randomized, double-blind trial, adding clonidine to
      standard opioid therapy for detoxification from in utero exposure to methadone or
      heroin reduced the duration of pharmacotherapy for neonatal abstinence without
      causing short-term adverse cardiovascular outcomes. A larger trial is indicated
      to determine long-term safety.

PMID- 19398465
TI  - Isolated cerebral cortical tears in children: aetiology, characterisation and
      differentiation from non-accidental head injury.
AB  - A wide spectrum of intracranial injuries has been described as complicating
      difficult birth, particularly following instrumental delivery. We describe five
      children in whom isolated cortical tears were observed on MRI. Four cases were
      characterised by a difficult instrumental delivery. None of the children
      developed long-term neurological sequelae. As far as we are aware, isolated
      cerebral cortical tears have not been reported previously although recognition of
      this injury pattern is important because of its possible misinterpretation as a
      marker of a non-accidental head injury. Other differential diagnoses that should
      be considered include cerebral infarcts, schizencephaly and accidental head
      injury. The importance of high-quality cross-sectional brain imaging in newborn
      infants with seizures is emphasised.

PMID- 19398466
TI  - Myocardial delayed enhancement in patients with pulmonary hypertension and right
      ventricular failure: evaluation by cardiac MRI.
AB  - In this study, we evaluated patients with pulmonary arterial hypertension (PAH)
      and impaired right ventricular function. We used cardiac MRI for the detection of
      myocardial delayed enhancement (MDE) and its possible association with other
      clinical variables. 20 patients (6 males and 14 females, aged 44.5+/-11 years; 15
      New York Heart Association class III, 5 class IV) with known PAH (13 idiopathic,
      7 resulting from chronic pulmonary embolism) were evaluated for the detection of
      MDE. Short-axis cine images of the heart were made for ventricular function
      assessment using a steady-state free precession sequence. For MDE evaluation, a
      short-axis phase-sensitive inversion recovery sequence was performed 10 min after
      intravenous administration of 0.2 mmol kg(-1) gadodiamide. Right ventricle (RV)
      systolic dysfunction, RV enlargement and RV hypertrophy were present in 20
      patients (RV ejection fraction, 21.5+/-7.2%; RV diastolic diameter, 5.97+/-0.79
      cm; RV wall thickness, 0.73+/-0.10 cm). 13 of the 20 patients (65%) were positive
      for MDE (10 anterior, 12 inferior). All 13 positive patients with MDE
      demonstrated small hyperintense areas at the insertion points of the RV free wall
      in the interventricular septum. We found no significant correlation between MDE
      and ejection fraction or other haemodynamic variables. In this study, MDE
      correlated positively only with the duration of disease. We found that septal MDE
      can be present in patients with PAH and impaired ventricular function. However,
      further studies are necessary to investigate this possible association and its
      prognostic implication.

PMID- 19398467
TI  - Gene expression profiling of preplate neurons destined for the subplate: genes
      involved in transcription, axon extension, neurotransmitter regulation, steroid
      hormone signaling, and neuronal survival.
AB  - During mammalian corticogenesis a series of transient cell layers establish
      laminar architectonics. The preplate, which forms from the earliest-generated
      neurons, separates into the marginal zone and subplate layer. To provide a
      systematic screen for genes involved in subplate development and function, we
      screened lines of transgenic mice, generated using bacterial artificial
      chromosome methodology (GENSAT Project), to identify transgenic lines of mice
      that express the enhanced green fluorescent protein (EGFP) reporter in preplate
      neurons destined for the subplate. Gene expression profiling of RNA purified from
      EGFP-positive neurons identified over 200 genes with enriched expression in
      future subplate neurons. Major classes of subplate-enriched genes included genes
      involved in transcriptional processes, cortical development, cell and axon
      motility, protein trafficking and steroid hormone signaling. Additionally, we
      identified 10 genes related to degenerative diseases of the cerebral and
      cerebellar cortex. Cre recombinase-based fate mapping of cells expressing
      Phosphodiesterase 1c (Pde1c) revealed beta-galactosidase positive cells in the
      ventricular zone, as well as the subplate, suggesting that subplate neurons and
      cortical projection neurons may be derived from common progenitors. These
      experiments therefore reveal genetic markers, which identify subplate neurons
      from the earliest stages of their development, and genes with enriched expression
      in subplate neurons during early stages of corticogenesis.

PMID- 19398468
TI  - Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial
      remodelling in canines.
AB  - AIMS: The present study was designed to decipher molecular mechanisms underlying
      nicotine's promoting atrial fibrillation (AF) by inducing atrial structural
      remodelling. METHODS AND RESULTS: The canine model of AF was successfully
      established by nicotine administration and rapid pacing. The atrial fibroblasts
      isolated from healthy dogs were treated with nicotine. The role of microRNAs
      (miRNAs) on the expression and regulation of transforming growth factor-beta1
      (TGF-beta1), TGF-beta receptor type II (TGF-betaRII), and collagen production was
      evaluated in vivo and in vitro. Administration of nicotine for 30 days increased
      AF vulnerability by approximately eight- to 15-fold in dogs. Nicotine stimulated
      remarkable collagen production and atrial fibrosis both in vitro in cultured
      canine atrial fibroblasts and in vivo in atrial tissues. Nicotine produced
      significant upregulation of expression of TGF-beta1 and TGF-betaRII at the
      protein level, and a 60-70% decrease in the levels of miRNAs miR-133 and miR-590.
      This downregulation of miR-133 and miR-590 partly accounts for the upregulation
      of TGF-beta1 and TGF-betaRII, because our data established TGF-beta1 and TGF
      betaRII as targets for miR-133 and miR-590 repression. Transfection of miR-133 or
      miR-590 into cultured atrial fibroblasts decreased TGF-beta1 and TGF-betaRII
      levels and collagen content. These effects were abolished by the antisense
      oligonucleotides against miR-133 or miR-590. The effects of nicotine were
      prevented by an alpha7 nicotinic acetylcholine receptor antagonist. CONCLUSION:
      We conclude that the profibrotic response to nicotine in canine atrium is
      critically dependent upon downregulation of miR-133 and miR-590.

PMID- 19398469
TI  - Cardiac peroxisome proliferator-activated receptor-alpha activation causes
      increased fatty acid oxidation, reducing efficiency and post-ischaemic functional
      loss.
AB  - AIMS: Myocardial fatty acid (FA) oxidation is regulated acutely by the FA supply
      and chronically at the transcriptional level owing to FA activation of peroxisome
      proliferator-activated receptor-alpha (PPARalpha). However, in vivo
      administration of PPARalpha ligands has not been shown to increase cardiac FA
      oxidation. In this study we have examined the cardiac response to in vivo
      administration of tetradecylthioacetic acid (TTA, 0.5% w/w added to the diet for
      8 days), a PPAR agonist with primarily PPARalpha activity. METHODS AND RESULTS:
      Despite the fact that TTA treatment decreased plasma concentrations of lipids [FA
      and triacylglycerols (TG)], hearts from TTA-treated mice showed increased mRNA
      expression of PPARalpha target genes. Cardiac substrate utilization, ventricular
      function, cardiac efficiency, and susceptibility to ischaemia-reperfusion were
      examined in isolated perfused hearts. In accordance with the mRNA changes,
      myocardial FA oxidation was increased 2.5-fold with a concomitant reduction in
      glucose oxidation. This increase in FA oxidation was abolished in PPARalpha-null
      mice. Thus, it appears that the metabolic effects of TTA on the heart must be
      owing to a direct stimulatory effect on cardiac PPARalpha. Hearts from TTA
      treated mice also showed a marked reduction in cardiac efficiency (because of a
      two-fold increase in unloaded myocardial oxygen consumption) and decreased
      recovery of ventricular contractile function following low-flow ischaemia.
      CONCLUSION: This study for the first time observed that in vivo administration of
      a synthetic PPARalpha ligand elevated FA oxidation, an effect that was also
      associated with decreased cardiac efficiency and reduced post-ischaemic
      functional recovery.

PMID- 19398472
TI  - UN warns that swine flu outbreak could turn into pandemic.

PMID- 19398473
TI  - New German law bans genetic tests of fetuses for adult illnesses.

PMID- 19398471
TI  - Effect of guideline based computerised decision support on decision making of
      multidisciplinary teams: cluster randomised trial in cardiac rehabilitation.
AB  - OBJECTIVE: To determine the extent to which computerised decision support can
      improve concordance of multidisciplinary teams with therapeutic decisions
      recommended by guidelines. DESIGN: Multicentre cluster randomised trial.
      PARTICIPANTS: Multidisciplinary cardiac rehabilitation teams in Dutch centres and
      their cardiac rehabilitation patients. INTERVENTIONS: Teams received an
      electronic patient record system with or without additional guideline based
      decision support. MAIN OUTCOME MEASURES: Concordance with guideline
      recommendations assessed for two standard rehabilitation treatments-exercise and
      education therapy-and for two new but evidence based rehabilitation treatments
      relaxation and lifestyle change therapy; generalised estimating equations were
      used to account for intra-cluster correlation and were adjusted for patient's
      age, sex, and indication for cardiac rehabilitation and for type and volume of
      centre. RESULTS: Data from 21 centres, including 2787 patients, were analysed.
      Computerised decision support increased concordance with guideline recommended
      therapeutic decisions for exercise therapy by 7.9% (control 84.7%; adjusted
      difference 3.5%, 95% confidence 0.1% to 5.2%), for education therapy by 25.7%
      (control 63.9%; adjusted difference 23.7%, 15.5% to 29.4%), and for relaxation
      therapy by 25.5% (control 34.1%; adjusted difference 41.6%, 25.2% to 51.3%). The
      concordance for lifestyle change therapy increased by 3.2% (control 54.1%;
      adjusted difference 7.1%, -2.9% to 18.3%). Computerised decision support reduced
      cases of both overtreatment and undertreatment. CONCLUSIONS: In a
      multidisciplinary team motivated to adopt a computerised decision support aid
      that assists in formulating guideline based care plans, computerised decision
      support can be effective in improving the team's concordance with guidelines.
      Therefore, computerised decision support may also be considered to improve
      implementation of guidelines in such settings. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN36656997.

PMID- 19398470
TI  - Protective ischaemia in patients: preconditioning and postconditioning.
AB  - Infarct size can be limited by reducing the determinants of infarct size or
      increasing collateral blood flow by treatment initiated before the ischaemic
      event. Reperfusion is the definitive treatment for permanently reducing infarct
      size and restoring some degree of contractile function to the affected
      myocardium. Innate survival mechanisms in the heart can be stimulated by short,
      non-lethal periods of ischaemia and reperfusion, applied either before or after
      the ischaemic event. Preconditioning, a series of transient intervals of
      ischaemia and reperfusion applied before the lethal 'index' ischaemic event, sets
      in motion molecular and cellular mechanisms that increase cardiomyocyte survival
      to a degree that had not hitherto been seen before. The cardioprotective
      ischaemic-reperfusion protocol applied at onset of reperfusion, termed
      'postconditioning' (Postcon), is also associated with significant
      cardioprotection that can be applied at the point of reperfusion treatment in the
      catheterization laboratory or operating room. Both preconditioning and Postcon
      have been successfully applied to the clinical setting and have been found to
      reduce infarct size and other attributes of post-ischaemic injury. This review
      will summarize the physiological preclinical data on preconditioning and Postcon
      that are relevant to their translation to clinical therapeutics and treatment.

PMID- 19398475
TI  - Arterial load reduction after cardiac resynchronization therapy: why does it
      change?

PMID- 19398476
TI  - How to handle stress and look after your mental health.

PMID- 19398477
TI  - Judith Mackay: brandishing a sword for health.

PMID- 19398478
TI  - Germany reviews its policy on HPV vaccination for 12-17 year olds.

PMID- 19398479
TI  - Alcohol linked deaths three times higher than official figures, MPs hear.

PMID- 19398482
TI  - Rwanda launches vaccination drive against pneumococcal disease in under 5s.

PMID- 19398483
TI  - Estrogen regulation of vascular endothelial growth factor in breast cancer in
      vitro and in vivo: the role of estrogen receptor alpha and c-Myc.
AB  - The role of c-Myc in estrogen regulation of vascular endothelial growth factor
      (VEGF) and of the vasculature function has been investigated in breast cancer
      cells and tumors. The studies were performed on MCF7 wild-type cells and MCF7
      35im clone, stably transfected with an inducible c-Myc gene. In vitro and ex vivo
      methods for investigating molecular events were integrated with in vivo magnetic
      resonance imaging of the vascular function. The results showed that the c-Myc
      upregulation by estrogen is necessary for the transient induction of VEGF
      transcription; however, overexpression of c-Myc alone is not sufficient for this
      induction. Furthermore, both c-Myc and the activated estrogen receptor alpha
      (ERalpha) were shown to co-bind the VEGF promoter in close proximity, indicating
      a novel mechanism for estrogen regulation of VEGF. Studies of long-term estrogen
      treatment and overexpression of c-Myc alone demonstrated regulation of stable
      VEGF expression levels in vitro and in vivo, maintaining steady vascular
      permeability in tumors. However, withdrawal of estrogen from the tumors resulted
      in increased VEGF and elevated vascular permeability, presumably due to hypoxic
      conditions that were found to dominate VEGF overexpression in cultured cells.
      This work revealed a cooperative role for ERalpha and c-Myc in estrogen
      regulation of VEGF and the ability of c-Myc to partially mimic estrogen
      regulation of angiogenesis. It also illuminated the differences in estrogen
      regulation of VEGF during transient and long-term sustained treatments and under
      different microenvironmental conditions, providing a complementary picture of the
      in vitro and in vivo results.

PMID- 19398484
TI  - Haemo-pneumothorax and haemoptysis in a patient with suspected Ehlers-Danlos
      syndrome.
AB  - We present a case of recurrent haemo-pneumothorax in a young female patient with
      previously undiagnosed Ehlers-Danlos syndrome (EDS). The patient presented with a
      spontaneous haemo-pneumothorax not associated with menstruation. Following
      further subsequent episodes, left lower lobectomy was performed. In the past, the
      patient had suffered recurrent atraumatic bilateral patella dislocations which
      were never fully investigated. Histology of the lung tissue revealed features
      suggestive of EDS. Haemothorax is a rare complication of type IV EDS. There are
      very few reported cases of pulmonary presentation of EDS type IV.

PMID- 19398485
TI  - Equivalent osteoblastic differentiation function of human mesenchymal stem cells
      from rheumatoid arthritis in comparison with osteoarthritis.
AB  - OBJECTIVE: To evaluate the osteoblastic differentiation of human mesenchymal stem
      cells (hMSCs) in patients with RA. METHODS: Heparinized bone marrow aspirate was
      obtained from patients with OA and RA. Mononuclear cells were cultured for 2
      weeks and a colony-forming assay was performed. The phenotype of cells was
      analysed by flow cytometry. Passage 2 cells were cultured with beta
      glycerophosphate (bGP) in the control group and bGP, ascorbic acid and
      dexamethasone in the differentiation group. After 2 weeks, ALP staining and
      activity were performed. After 3 weeks, Alizarin Red S assay was performed. Total
      RNA was extracted from cells cultured for 2 and 3 weeks. Gene expression of bone
      formation factor was examined by real-time PCR. RESULTS: The phenotype of cells
      was identical in both OA and RA and the content was thought to be hMSCs. The
      results of ALP activity and Alizarin Red S assay showed higher levels in the
      differentiation group for both OA and RA samples compared with the control group.
      The results of a colony-forming assay were identical in both OA and RA samples.
      Gene expression in the differentiation group was higher than in the control group
      in both OA and RA samples. There was no significant difference between OA and RA
      samples in all experiments. CONCLUSION: The function of osteoblastic
      differentiation of hMSCs is similar between OA and RA.

PMID- 19398487
TI  - Monozygotic twins with distinct forms of idiopathic inflammatory myositis.

PMID- 19398486
TI  - An update on the epidemiology of calcium pyrophosphate dihydrate crystal
      deposition disease.
AB  - The aim of this review is to summarize recent research relating to the
      epidemiology of chondrocalcinosis (CC), including prevalence of CC, the
      association between CC and OA, familial forms of CC and diseases associated with
      CC. We searched MEDLINE for articles published in English from 1998 to 2008 using
      MEsH terms covering all aspects of the epidemiology of CC. Aging is the main risk
      factor for the occurrence of sporadic CC. Prevalence of CC varies from 7 to 10%
      in people aged approximately 60 years and shows equal sex distribution. There is
      a positive association between CC and OA, but CC does not appear to be a risk
      factor for subsequent structural progression in terms of cartilage loss.
      Mutations in the ankylosis human (ANKH) gene have been identified as a cause of
      familial CC in some kindreds. There is good evidence that hereditary
      haemochromatosis, hyperparathyroidism and hypomagnesaemia are metabolic disorders
      that predispose to secondary CC. In conclusion, sporadic CC is a common condition
      in the elderly and frequently associates with OA. Primary metabolic disorders or
      familial predisposition are uncommon but should be considered if CC occurs before
      55 years of age or if there is florid polyarticular CC. After the age of 55
      years, hyperparathyroidism should be considered in all patients.

PMID- 19398488
TI  - Long-term prognosis of medically treated patients with functional mitral
      regurgitation and left ventricular dysfunction.
AB  - AIMS: To assess long-term prognosis in patients with functional mitral
      regurgitation (FMR) and left ventricular (LV) dysfunction, receiving current
      standard pharmacological therapy. METHODS AND RESULTS: We prospectively enrolled
      404 consecutive patients (mean age 70.2 +/- 10 years) with ischaemic (76.5%) and
      non-ischaemic (23.5%) LV dysfunction (ejection fraction 34.4 +/- 10.8%) and at
      least mild MR. Results are reported at 4 years' follow-up. Survival free of all
      cause mortality was 53% and cardiac death was 74%. Survival free of all-cause
      mortality was 50% (95% CI 35-72) for patients with moderate MR, 49% (95% CI 27
      65) for severe MR, and 64% (95% CI 47-78) for mild MR (P = 0.03). Survival free
      of cardiac death was 57% (95% CI 38-74) for patients with moderate MR, 55% (95%
      CI 30-77) for severe MR, and 94% (95% CI 59-98) for mild MR (P = 0.003). Moderate
      to-severe MR [relative risk (RR) 2.7, 95% CI 1.2-6.1, P = 0.003] was an
      independent predictor of cardiac death but not of all-cause mortality. Survival
      free of heart failure (HF) was 32%. Survival free of HF was 20% (95% CI 17-35)
      for patients with moderate MR, 18% (95% CI 15-32) for severe MR, and 62% (95% CI
      45-72) for mild MR (P = 0.0001). Moderate-to-severe MR (RR 3.2, 95% CI 1.9-5.2, P
      = 0.0001) was an independent predictor of HF. CONCLUSION: The mortality and
      morbidity of patients with LV dysfunction and FMR remain high despite current
      standard pharmacological therapy. Moderate-to-severe MR is an independent
      predictor of cardiac death and HF.

PMID- 19398490
TI  - Influence of gender of physicians and patients on guideline-recommended treatment
      of chronic heart failure in a cross-sectional study.

PMID- 19398491
TI  - Mapping of the domestic cat "SILVER" coat color locus identifies a unique genomic
      location for silver in mammals.
AB  - The SILVER locus has been mapped in the domestic cat, identifying a unique
      genomic location distinct from that of any known reported gene associated with
      silver or hypopigmentation in mammals. A demonstrated lack of linkage to SILV,
      the strong candidate gene for silver, led to the initiation of a genome scan
      utilizing 2 pedigrees segregating for silver coat color. Linkage mapping defined
      a genomic region for SILVER as a 3.3-Mb region, (95.87-99.21 Mb) on chromosome
      D2, (peak logarithm of the odds = 10.5, = 0), which displays conserved synteny to
      a genomic interval between 118.58 and 121.85 Mb on chromosome 10 in the human
      genome. In the domestic cat, mutations at the SILVER locus suppress the
      development of pigment in the hair, but in contrast to other mammalian silver
      variants, there is an apparently greater influence on the production of
      pheomelanin than eumelanin pigment. The mapping of a novel locus for SILVER
      offers much promise in identifying a gene that may help elucidate aspects of
      pheomelanogenesis, a pathway that has been very elusive, and illustrates the
      promise of the cat genome project in increasing our understanding of basic
      biological processes of general relevance for mammals.

PMID- 19398492
TI  - Positive selection has driven the evolution of the Drosophila insulin-like
      receptor (InR) at different timescales.
AB  - The highly conserved insulin-signaling pathway influences very diverse processes
      including intermediary metabolism, reproduction, aging, and growth. The first
      pathway component is the insulin receptor that upon insulin binding triggers the
      signal-transduction cascade. Its variation, like that of other pathway
      components, might therefore affect many organismal traits. Variation at the
      "Insulin-like" receptor (InR) gene was surveyed both within Drosophila
      melanogaster and between species across the Drosophila phylogeny. In D.
      melanogaster, the level and pattern of variation at the approximately 8-kb region
      surveyed did not provide any indication of a recent selective event in this
      region. Maximum likelihood (ML) analyses revealed the past action of purifying
      selection acting differentially both across the phylogeny and along the studied
      gene. Moreover, the ML analyses and the McDonald and Kreitman test revealed the
      footprint of positive selection driving amino acid changes to fixation in the
      branch separating the Sophophora and the Drosophila subgenera, and in the D.
      melanogaster lineage, respectively. The oldest selective events could have
      affected either the insulin binding or the signal-transduction capacities of the
      receptor, whereas mutations affecting signal transduction would seem to underlie
      the more recent events.

PMID- 19398493
TI  - Adaptive gene loss reflects differences in the visual ecology of basal
      vertebrates.
AB  - The agnathans (lampreys and hagfishes) are representatives of the jawless fishes
      and constitute the first lineage of extant vertebrates to evolve within chordate
      phylogenetic history. Previously, we showed that the southern hemisphere pouched
      lamprey Geotria australis has the potential for pentachromacy with the expression
      of five visual pigment (opsin) genes (LWS, SWS1, SWS2, RhA, and RhB) in five
      different cone-like photoreceptors for life in a brightly lit environment exposed
      to a broad spectrum of light. In contrast, the northern hemisphere sea lamprey
      Petromyzon marinus dwells in a wide range of depths that are relatively deeper
      than the epipelagic waters inhabited by G. australis. Thus, the light levels of
      the habitat in which the sea lamprey resides are greatly diminished and different
      regions of the light spectrum are differentially absorbed. Therefore, the visual
      systems of these two species of lamprey constitute a natural experiment in which
      to study the selection pressures underlying opsin gene expression and the
      evolution of color discrimination. By analyzing the opsin genes of P. marinus, we
      show the expression of two intact retinal opsins, RhA and LWS, which, when
      regenerated with 11-cis retinal, give peak spectral sensitivities (lambda(max)
      values) of 501 and 536 nm, respectively. In contrast to G. australis, the genome
      of P. marinus possesses remnants of SWS1 and SWS2 pseudogenes, which with the
      loss of RhB, suggests that P. marinus is a dichromat. Using site-directed
      mutagenesis, we show that a single amino acid substitution (Ser to Pro) at site
      164 is responsible for a blue shift of 19 nm of the LWS visual pigment of P.
      marinus compared with G. australis, which may reflect habitat differences between
      the two species. Based on these studies, we propose that gene loss (or
      duplication) and subsequent mutation plays an important role in the evolution of
      color vision and that the complement and tuning of these visual pigments reflect
      the ecology and light environment of these phylogenetically basal vertebrates.

PMID- 19398494
TI  - Cold-inducible RNA binding protein (CIRP) expression is modulated by alternative
      mRNAs.
AB  - Cold-inducible RNA binding protein (CIRP) is a mammalian protein whose expression
      is up-regulated in response to mild hypothermia. Although the exact function of
      this protein is currently unknown, it is thought to function as an RNA chaperone,
      facilitating mRNA translation upon the perception of cold stress. In this study
      we have identified and characterized the major CIRP 5'-untranslated region (5'
      UTR) transcripts in mouse embryonic fibroblast NIH-3T3 cells. We show that the 5'
      UTR of CIRP, a protein highly homologous to the cold-shock protein Rbm3, is much
      shorter than the previously published 5' leader sequence of Rbm3. In addition,
      three major CIRP transcripts with different transcription start sites are
      generated, with the levels of each of these transcripts being regulated in
      response to time and temperature. The major transcript generated at 37 degrees C
      does not encode for the full-length CIRP open reading frame, while the two major
      transcripts at 32 degrees C do. Further, the longest transcript detected at 32
      degrees C shows a discrete expression and stability profile under mild
      hypothermic conditions and exhibits internal ribosome entry segment (IRES)-like
      activity. The IRES-like activity is not responsive to conditions of mild
      hypothermia or hypoxia, but the levels and stability of the transcript harboring
      the putative IRES are increased at 32 degrees C. We discuss the emerging
      transcriptional and translational mechanisms by which CIRP expression appears to
      be controlled and the role that the 5'-UTR plays in the modulation of CIRP
      expression.

PMID- 19398496
TI  - Preliminary evidence of immune function modulation by thyroid hormones in healthy
      men and women aged 55-70 years.
AB  - A reciprocal relationship between the endocrine and immune system has been
      demonstrated under pathophysiological conditions. However, few studies have
      assessed the relationship between thyroid hormones and immune function in
      apparently healthy individuals. Therefore, to clarify our understanding of normal
      physiological endocrine-immune interactions this study aimed to examine the
      interrelationships between thyroid hormones and immunity in healthy individuals.
      Total triiodothyronine (T(3)), total thyroxine (T(4)) and markers of immune
      status were assessed in 93 free-living and apparently healthy individuals aged 55
      70 years. T(3) and T(4) concentrations were determined by commercially available
      kits. Immune status was assessed using flow cytometry and biochemical markers.
      Statistical analysis was performed by partial correlation, controlling for age.
      Thyroid hormone concentration was positively associated with markers of
      inflammation (P<or=0.05), natural killer-like T cells (P<or=0.001), expression of
      interleukin-6 (IL6) by activated monocytes (P<or=0.05); percentage expression of
      memory T-lymphocytes (P<or=0.01), memory T-helper lymphocytes (P<or=0.05) and
      memory T-cytotoxic lymphocytes (P<or=0.05), and higher IL2 receptor density on
      CD3+T-lymphocytes (P<or=0.05). Thyroid hormone concentration was inversely
      associated with early lymphocyte apoptosis (P<or=0.05) and the ratio of naive- to
      memory T-cytotoxic lymphocytes (P<or=0.05). The current study provides
      preliminary evidence of a role for T(3) and T(4), within normal physiological
      ranges, in the maintenance of lymphocyte subpopulations, and in mediating the
      inflammatory response. In conclusion, these findings highlight the potential
      implications of altered thyroid function in older individuals and the importance
      of future research examining thyroid-immune interactions.

PMID- 19398495
TI  - Mammalian GW182 contains multiple Argonaute-binding sites and functions in
      microRNA-mediated translational repression.
AB  - In mammalian cells, microRNAs (miRNAs) are incorporated into miRNA-induced
      silencing complexes (miRISCs), which regulate protein expression post
      transcriptionally through binding to 3'-untranslated regions of target mRNAs.
      Argonaute2 (Ago2), a key component of the miRISC, recruits GW182, a component of
      the processing body (GW/P-body), to the target mRNAs. To elucidate the function
      of GW182 in an miRNA-mediated translational repression, we analyzed Argonaute
      binding sites in GW182. We found that human GW182 contains three binding sites
      for Ago2, within the amino-terminal glycine tryptophan (GW/WG)-repeated region
      that is characteristic of the GW182 family proteins. We also found that the first
      and second Ago2-binding site is conserved within the amino-terminal half of
      TNRC6B, which is a paralog of GW182. Each of the Ago-binding sites is alone
      sufficient to bind Ago2. Furthermore, we demonstrated that multiple Argonaute
      proteins were connected via the GW182 protein. A GW182 fragment containing the
      Ago2-binding region partially relieved let-7-mediated repression of protein
      synthesis in a mammalian cell-free system. Coincidentally, let-7-directed target
      mRNA deadenylation was delayed. Together, these results strongly suggested that
      the interactions of GW182 with Argonautes may induce the formation of large
      complexes containing miRNA target mRNAs, and may be critical for miRNA-mediated
      translational repression.

PMID- 19398497
TI  - Exendin-4 inhibits interleukin-1beta-induced iNOS expression at the protein
      level, but not at the transcriptional and posttranscriptional levels, in RINm5F
      beta-cells.
AB  - Cytokines such as interleukin-1beta (IL-1beta) stimulate inducible nitric oxide
      synthase (iNOS) expression and nitric oxide overproduction leading to beta-cell
      damage. Meanwhile, glucagon-like peptide-1 (GLP-1) and its potent analog exendin
      4 (EX-4) were well known for beta-cell proliferation. However, the protective
      mechanisms of GLP-1 in beta-cells exposed to cytokines were not fully elucidated.
      Therefore, the effects of EX-4 on the IL-1beta-induced iNOS gene expression were
      investigated employing RINm5F beta-cells. EX-4 inhibited IL-1beta-induced iNOS
      protein expression and nitrite production. However, northern blot and promoter
      analyses showed that EX-4 failed to inhibit IL-1beta-induced iNOS mRNA expression
      and iNOS promoter activity. By electrophoretic mobility shift assay (EMSA), EX-4
      did not alter the binding activity of NF-kappaB to the iNOS promoter. Consistent
      with the EMSA result, EX-4 did not inhibit nuclear translocation of p65. We also
      tested the effect of EX-4 on iNOS mRNA stability. Actinomycin D chase experiments
      showed that EX-4 did not affect the decay rate of iNOS mRNA and the promoter
      assay using the construct containing 3'-untranslated region of iNOS showed that
      EX-4 did not alter the stability of iNOS mRNA. Meanwhile, forskolin significantly
      inhibited IL-1beta-induced iNOS protein, which was reversed by H-89, a protein
      kinase A (PKA) inhibitor. Moreover, EX-4 pretreatment restored IL-1beta-induced
      decrease in cAMP toward control level. Additionally, the cycloheximide chase
      study demonstrated that EX-4 significantly accelerated iNOS protein degradation.
      We therefore concluded that EX-4 inhibited IL-1beta-induced iNOS protein and
      nitrite production via cAMP/PKA system irrespective of both transcriptional and
      posttranscriptional mechanisms of iNOS gene, and this inhibitory effect of EX-4
      appears to be regulated at posttranslational level.

PMID- 19398498
TI  - A new mouse model of metabolic syndrome and associated complications.
AB  - Metabolic syndrome (MS) encompasses a clustering of risk factors for
      cardiovascular disease, including obesity, insulin resistance, and dyslipidemia.
      We characterized a new mouse model carrying a dominant mutation, C57BL/6J-Nmf15/+
      (B6-Nmf15/+), which develops additional complications of MS such as adipose
      tissue inflammation and cardiomyopathy. A backcross was used to genetically map
      the Nmf15 locus. Mice were examined in the comprehensive laboratory animal
      monitoring system, and dual energy X-ray absorptiometry and blood chemistry
      analyses were performed. Hypothalamic LEPR, SOCS1, and STAT3 phosphorylation were
      examined. Cardiac function was assessed by echo- and electrocardiography. Adipose
      tissue inflammation was characterized by in situ hybridization and measurement of
      Jun kinase activity. The Nmf15 locus mapped to distal mouse chromosome 5 with an
      LOD (logarithm of odds) score of 13.8. Nmf15 mice developed obesity by 12 weeks
      of age. Plasma leptin levels were significantly elevated in pre-obese Nmf15 mice
      at 8 weeks of age and an attenuated STAT3 phosphorylation in the hypothalamus
      suggests a primary leptin resistance. Adipose tissue from Nmf15 mice showed a
      remarkable degree of inflammation and macrophage infiltration as indicated by
      expression of the F4/80 marker and increased phosphorylation of JUN N-terminal
      kinase 1/2. Lipidosis was observed in tubular epithelial cells and glomeruli of
      the kidney. Nmf15 mice demonstrate both histological and pathophysiological
      evidence of cardiomyopathy. The Nmf15 mouse model provides a new entry point into
      pathways mediating leptin resistance and obesity. It is one of few models that
      combine many aspects of MS and can be useful for testing new therapeutic
      approaches for combating obesity complications, particularly cardiomyopathy.

PMID- 19398499
TI  - Initial evidence of a failure to activate right anterior insula during affective
      set shifting in posttraumatic stress disorder.
AB  - OBJECTIVE: Interoception is the sense of one's internal physiological, sensory,
      and emotional status. Extensive evidence supports a link between interoception
      and subjective experience. An altered ability to monitor or modulate
      interoception as it relates to subjective experience may provide a mechanistic
      explanation for the development of some forms of psychiatric illness. METHODS: We
      investigated which neural networks are activated when anticipating a change in
      affective (and thus interoceptive) state, which we term "affective set-shifting,"
      in 15 women with posttraumatic stress disorder (PTSD) related to intimate partner
      violence, and in 15 nontraumatized healthy volunteers. RESULTS: Although both
      groups activated the dorsolateral prefrontal cortex during affective set
      shifting, the PTSD group showed significantly less activation in the right
      anterior insula than did the controls. CONCLUSIONS: These findings may suggest
      that although individuals with PTSD are cognitively aware of the impending shift
      in interoceptive state, they fail to appropriately activate neural circuitry
      involved in modulating interoceptive responses.

PMID- 19398500
TI  - Reverse causation in the association between C-reactive protein and fibrinogen
      levels and cognitive abilities in an aging sample.
AB  - OBJECTIVE: To test the hypothesis that increased levels of inflammatory and
      hemostatic markers are associated with poorer cognitive performance and to assess
      the influence of childhood intelligence quotient (IQ) and current cardiovascular
      disease (CVD) risk factors on this relationship. Blood inflammatory markers have
      been shown to predict late-life cognition, although the mechanism through which
      this occurs is unknown. METHODS: Levels of the biomarkers C-reactive protein and
      fibrinogen were measured in 1053 Scottish participants (50.2% female) from the
      Lothian Birth Cohort 1936 ranging in age from 67 to 71 years. Biomarker levels
      were tested for their association with diverse cognitive abilities. RESULTS:
      Significant cross-sectional associations were found between the biomarkers and
      various cognitive abilities: their effect size was around 1% of the variance and
      was in the direction of higher marker levels conferring poorer cognitive
      performance. With the exception of the reaction time measures (and fibrinogen),
      these associations could be explained by childhood IQ, CVD risk factors, or both.
      Importantly, both the inflammatory markers at age 70 years were associated (p <
      .001) with childhood IQ. CONCLUSIONS: Whereas inflammatory marker levels predict
      contemporaneous general cognitive ability, the results support a model of reverse
      causation because childhood IQ predicts late-life inflammation. This might be
      through its association with later life CVD risk factors or because it is a
      measure of system integrity. Unlike general cognitive ability, the association
      between inflammatory markers (particularly fibrinogen) and processing speed was
      maintained in the presence of childhood IQ and/or CVD risk factor adjustments.
      This might also reflect variation in physiological integrity.

PMID- 19398502
TI  - Characterization of the binding of drugs to human intestinal fatty acid binding
      protein (IFABP): potential role of IFABP as an alternative to albumin for in
      vitro-in vivo extrapolation of drug kinetic parameters.
AB  - This work characterized for the first time the binding of acidic, neutral, and
      basic drugs to human intestinal fatty acid binding protein (IFABP) and, for
      comparison, to bovine serum albumin (BSA). In addition, the study investigated
      whether IFABP can substitute for BSA as a constituent in incubations of human
      liver microsomes (HLMs) in in vitro-in vivo extrapolation (IV-IVE) studies. Each
      molecule of purified IFABP bound a single molecule of the fluorescent probe 1
      anilino-8-naphthalene sulfonate or arachidonic acid with K(d) values similar to
      those reported for rat IFABP. Basic drugs bound negligibly to IFABP. Based on
      fraction unbound (f(u)) at a protein concentration of 0.5% (w/v), binding of
      acidic and neutral drugs ranged from minor (f(u) > 0.8) to moderate (f(u) 0.5
      0.8). Of the compounds screened, highest binding to IFABP was observed for
      sulfinpyrazone (an acid) and beta-estradiol (a neutral compound). However,
      binding to IFABP was lower than to BSA for all the drugs investigated. To
      determine the potential suitability of IFABP as an alternative to BSA for
      enhancing the prediction accuracy of IV-IVE based on human liver microsomal
      kinetic data, the kinetics of zidovudine (AZT) glucuronidation by HLM were
      characterized in the absence and presence of BSA and IFABP (0.5-2.5%, w/v). Each
      protein reduced the K(m) for AZT glucuronidation in a concentration-dependent
      manner, although a higher content of IFABP in incubations (2.5 versus 1-1.5% for
      BSA) was necessary for a 10-fold reduction in this parameter. The results
      indicate that IFABP is likely to have advantages over BSA in microsomal kinetic
      studies with drugs that bind extensively to albumin.

PMID- 19398501
TI  - Depressive symptoms and increased visceral fat in middle-aged women.
AB  - OBJECTIVE: To examine whether depressive symptoms are differentially associated
      with visceral adipose tissue (VAT), which is more metabolically active and
      confers greater cardiovascular risk than subcutaneous fat (SAT). Prior research
      has shown an association between depression and central adiposity. Mechanisms
      underlying the association between depression and increased cardiovascular risk
      remain poorly understood. Central adiposity is one potential pathway. METHODS: We
      investigated the cross-sectional association between depressive symptoms,
      assessed by the Center for Epidemiological Studies Depression Scale (CES-D), and
      VAT and SAT, assessed by computed tomography, in a sample of 409 middle-aged
      women (44.7% African-Americans, 55.3% Whites; mean age = 50.4 years)
      participating in the Chicago site of the Study of Women's Health Across the
      Nation (SWAN). RESULTS: With adjustments for age, race, total percent fat, and
      sex hormone binding globulin (SHBG), each 1-point higher score on the CES-D was
      associated with 1.03-cm(2) greater VAT (p < .001). Women with a CES-D score of
      >or=16, indicative of clinically relevant depressive symptomatology, had 24.5%
      more VAT than women with lower CES-D scores (p < .001). Further adjustment for
      Framingham Risk Score and physical activity did not alter the findings, and
      associations did not vary by race. Associations were strongest in obese and
      overweight women. Depressive symptoms were unrelated to SAT. CONCLUSIONS:
      Increased visceral fat may be one pathway by which depression contributes to
      excess risk for cardiovascular disease and diabetes. Further research is needed
      to examine whether depressive symptoms influence accumulation of VAT over time.

PMID- 19398503
TI  - Molecular basis for reduced estrone sulfate transport and altered modulator
      sensitivity of transmembrane helix (TM) 6 and TM17 mutants of multidrug
      resistance protein 1 (ABCC1).
AB  - Multidrug resistance protein 1 (MRP1) confers drug resistance and also mediates
      cellular efflux of many organic anions. MRP1 also transports glutathione (GSH);
      furthermore, this tripeptide stimulates transport of several substrates,
      including estrone 3-sulfate. We have previously shown that mutations of Lys(332)
      in transmembrane helix (TM) 6 and Trp(1246) in TM17 cause different substrate
      selective losses in MRP1 transport activity. Here we have extended our
      characterization of mutants K332L and W1246C to further define the different
      roles these two residues play in determining the substrate and inhibitor
      specificity of MRP1. Thus, we have shown that TM17-Trp(1246) is crucial for
      conferring drug resistance and for binding and transport of methotrexate,
      estradiol glucuronide, and estrone 3-sulfate, as well as for binding of the
      tricyclic isoxazole inhibitor N-[3-(9-chloro-3-methyl-4-oxo-4H-isoxazolo-[4,3
      c]quinolin-5-yl)-cyclohexylmethyl]-benzamide (LY465803). In contrast, TM6
      Lys(332) is important for enabling GSH and GSH-containing compounds to serve as
      substrates (e.g., leukotriene C(4)) or modulators (e.g., S-decyl-GSH, GSH
      disulfide) of MRP1 and, further, for enabling GSH (or S-methyl-GSH) to enhance
      the transport of estrone 3-sulfate and increase the inhibitory potency of
      LY465803. On the other hand, both mutants are as sensitive as wild-type MRP1 to
      the non-GSH-containing inhibitors (E)-3-[[[3-[2-(7-chloro-2
      quinolinyl)ethenyl]phenyl][[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]
      propanoic acid (MK571), 1-[2-hydroxy-3-propyl-4-[4-(1H-tetrazol-5
      yl)butoxy]phenyl]-ethanone (LY171883), and highly potent 6-[4'-carboxyphenylthio]
      5[S]-hydroxy-7[E], 11[Z]14[Z]-eicosatetrenoic acid (BAY u9773). Finally, the
      differing abilities of the cysteinyl leukotriene derivatives leukotriene C(4),
      D(4), and F(4) to inhibit estradiol glucuronide transport by wild-type and K332L
      mutant MRP1 provide further evidence that TM6-Lys(332) is involved in the
      recognition of the gamma-Glu portion of substrates and modulators containing GSH
      or GSH-like moieties.

PMID- 19398504
TI  - Quantitative proteomics: the next logical step in molecular phenotyping.

PMID- 19398505
TI  - Quantitative strategies to fuel the merger of discovery and hypothesis-driven
      shotgun proteomics.
AB  - The ultimate goal of most shotgun proteomic pipelines is the discovery of novel
      biomarkers to direct the development of quantitative diagnostics for the
      detection and treatment of disease. Differential comparisons of biological
      samples identify candidate peptides that can serve as proxys of candidate
      proteins. While these discovery approaches are robust and fairly comprehensive,
      they have relatively low throughput. When merged with targeted mass spectrometry,
      this pipeline can fuel hypothesis-driven studies and the development of novel
      diagnostics and therapeutics.

PMID- 19398506
TI  - Flow and performance of an air-curtain biological safety cabinet.
AB  - Using laser-assisted smoke flow visualization and tracer gas concentration
      detection techniques, this study examines aerodynamic flow properties and the
      characteristics of escape from containment, inward dispersion, and cross-cabinet
      contamination of a biological safety cabinet installed with an air curtain across
      the front aperture. The experimental method partially simulates the NSF/ANSI 49
      standards with the difference that the biological tracer recommended by these
      standards is replaced by a mixture of 10% SF(6) in N(2). The air curtain is set
      up across the cabinet aperture plane by means of a narrow planar jet issued from
      the lower edge of the sash and a suction flow going through a suction slot
      installed at the front edge of the work surface. Varying the combination of jet
      velocity, suction flow velocity, and descending flow velocity reveals three types
      of characteristic flow modes: 'straight curtain', 'slightly concave curtain', and
      'severely concave curtain'. Operating the cabinet in the straight curtain mode
      causes the air curtain to impinge on the doorsill and therefore induces serious
      escape from containment. In the severely concave curtain mode, drastically large
      inward dispersion and cross-cabinet contamination were observed because
      environmental air entered into the cabinet and a three-dimensional vortical flow
      structure formed in the cabinet. The slightly concave curtain mode presents a
      smooth and two-dimensional flow pattern with an air curtain separating the
      outside atmosphere from the inside space of the cabinet, and therefore exhibited
      negligibly small escape from containment, inward dispersion, and cross-cabinet
      contamination.

PMID- 19398507
TI  - Fate and transport of antibiotic residues and antibiotic resistance genes
      following land application of manure waste.
AB  - Antibiotics are used in animal livestock production for therapeutic treatment of
      disease and at subtherapeutic levels for growth promotion and improvement of feed
      efficiency. It is estimated that approximately 75% of antibiotics are not
      absorbed by animals and are excreted in waste. Antibiotic resistance selection
      occurs among gastrointestinal bacteria, which are also excreted in manure and
      stored in waste holding systems. Land application of animal waste is a common
      disposal method used in the United States and is a means for environmental entry
      of both antibiotics and genetic resistance determinants. Concerns for bacterial
      resistance gene selection and dissemination of resistance genes have prompted
      interest about the concentrations and biological activity of drug residues and
      break-down metabolites, and their fate and transport. Fecal bacteria can survive
      for weeks to months in the environment, depending on species and temperature,
      however, genetic elements can persist regardless of cell viability. Phylogenetic
      analyses indicate antibiotic resistance genes have evolved, although some genes
      have been maintained in bacteria before the modern antibiotic era. Quantitative
      measurements of drug residues and levels of resistance genes are needed, in
      addition to understanding the environmental mechanisms of genetic selection, gene
      acquisition, and the spatiotemporal dynamics of these resistance genes and their
      bacterial hosts. This review article discusses an accumulation of findings that
      address aspects of the fate, transport, and persistence of antibiotics and
      antibiotic resistance genes in natural environments, with emphasis on mechanisms
      pertaining to soil environments following land application of animal waste
      effluent.

PMID- 19398508
TI  - Content and binding forms of heavy metals, aluminium and phosphorus in bog iron
      ores from Poland.
AB  - Bog iron ores are widespread in Polish wetland soils used as meadows or pastures.
      They are suspected to contain high concentrations of heavy metals, which are
      precipitated together with Fe along a redox gradient. Therefore, soils with bog
      iron ore might be important sources for a heavy metal transfer from meadow plants
      into the food chain. However, this transfer depends on the different binding
      forms of heavy metals. The binding forms were quantified by sequential extraction
      analysis of heavy metals (Fe, Mn, Cr, Co, Ni, Cd, Pb) as well as Al and P on 13
      representative samples of bog iron ores from central and southwestern Poland. Our
      results showed total contents of Cr, Co, Ni, Zn, Cd, and Pb not to exceed the
      natural values for sandy soils from Poland. Only the total Mn was slightly
      higher. The highest contents of all heavy metals have been obtained in iron oxide
      fractions V (occluded in noncrystalline and poorly crystalline Fe oxides) and VI
      (occluded in crystalline Fe oxides). The results show a distinct relationship
      between the content of Fe and the quantity of Zn and Pb as well P. Water soluble
      as well as plant available fractions were below the detection limit in most
      cases. From this we concluded bog iron ores not to be an actual, important source
      of heavy metals in the food chain. However, a remobilization of heavy metals
      might occur due to any reduction of iron oxides in bog iron ores, for example, by
      rising groundwater levels.

PMID- 19398509
TI  - Use of ochre from an abandoned metal mine in the south east of Ireland for
      phosphorus sequestration from dairy dirty water.
AB  - Ochre found at coal mine drainage sites in the United Kingdom shows a high
      phosphorus (P) retention capacity with little mobilization of metals. This
      indicates that ochre has the potential to adsorb P from agricultural wastewaters
      for possible use as a fertilizer. Little research has focused on the ability of
      metal mine ochre to sequester P in an environmentally sustainable way. Untreated
      acid mine drainage from an abandoned copper-sulfur mine in the Avoca-Avonmore
      catchment in the south east of Ireland results in extensive low-value ochre
      deposition. In this study, P-amended water (50 mL) was mixed with this ochre (2.5
      g) in batch experiments, and a maximum P adsorption capacity, calculated from the
      Langmuir equation, of between 16 and 21 g P kg(-1) was calculated. However,
      mobilization of heavy metals from Avoca ochre in distilled, surface, and dirty
      water batch experiments was observed. This mobilization may inhibit ochre's use
      in P removal from wastewaters.

PMID- 19398510
TI  - Predictions of spatially averaged cadmium contents in rice grains in the Fuyang
      Valley, P.R. China.
AB  - Soils in the Fuyang valley (Zhejiang province, southeast China) have been
      contaminated by heavy metals. Since rice (Oryza sativa L.) is the dominant crop
      in the valley and because of its tendency to accumulate Cd in its grains,
      assessment of the human health risk resulting from consumption of locally
      produced rice is needed. In this study, we used a regression model to predict the
      average Cd content in rice grains for paddy fields. The multiple linear model for
      log(Cd) content in rice grains with log(HNO(3)-Cd), pH, log(clay), and log(soil
      organic matter, SOM) as predictors performed much better (R(2)(adj) = 66.1%) than
      the model with log(CaCl(2)-Cd) as a single predictor (R(2)(adj) = 28.1%). This
      can be explained by the sensitivity of CaCl(2)-extracted Cd for changes in redox
      potential and as a result of the drying of the soil samples in the laboratory.
      Consequently, the multiple linear model was used to predict the average Cd
      contents in rice grains for paddy fields, and to estimate the probability that
      the FAO/WHO standard of 0.2 mg kg(-1) will be exceeded. Eleven blocks had a
      probability smaller than 10% of exceeding this standard (safe blocks). If a
      lognormal distribution is assumed, 35 blocks had a probability larger than 90%
      (blocks at risk). Hence, risk reduction measures should be undertaken for the
      blocks at risk. For 27 blocks the probability was between 10 and 90%. For these
      blocks the uncertainty should be reduced via improvement of the regression model
      and/or increasing the number of sample locations within blocks.

PMID- 19398511
TI  - Uncertainties in data and models to describe event dynamics of agricultural
      sediment and phosphorus transfer.
AB  - Mathematical models help to quantify agricultural sediment and phosphorus
      transfers and to simulate mitigation of pollution. This paper develops empirical
      models of the dominant sediment and phosphorus event dynamics observed at high
      resolution in a drained and undrained, intensive grassland field-scale lysimeter
      (1 ha) experiment. The uncertainties in model development and simulation are
      addressed using Generalized Likelihood Uncertainty Estimation. A comparison of
      suspended solids (SS) and total phosphorus (TP) samples with a limited number of
      manual repeats indicates larger data variability at low flows. Quantitative
      uncertainty estimates for discharge (Q) are available from another study.
      Suspended solids-discharge (SS-Q) hysteresis is analyzed for four events and two
      drained and two undrained fields. Hysteresis loops differ spatially and
      temporally, and exhaustion is apparent between sequential hydrograph peaks. A
      coherent empirical model framework for hysteresis, where SS is a function of Q
      and rate of change of Q, is proposed. This is evaluated taking the Q uncertainty
      into account, which can contribute substantially to the overall uncertainty of
      model simulations. The model simulates small hysteresis loops well but fails to
      simulate exhaustion of SS sources and flushing at the onset of events. Analysis
      of the TP-SS relationship reveals that most of the variability occurs at low
      flows, and a power-law relationship can explain the dominant behavior at higher
      flows, which is consistent across events, fields, and pathways. The need for
      further field experiments to test hypotheses of sediment mobilization and to
      quantify data uncertainties is identified.

PMID- 19398512
TI  - Sources and transformations of nitrate from streams draining varying land uses:
      evidence from dual isotope analysis.
AB  - Knowledge of key sources and biogeochemical processes that affect the transport
      of nitrate (NO(3)(-)) in streams can inform watershed management strategies for
      controlling downstream eutrophication. We applied dual isotope analysis of NO(3)(
      ) to determine the dominant sources and processes that affect NO(3)(-)
      concentrations in six stream/river watersheds of different land uses. Samples
      were collected monthly at a range of flow conditions for 15 mo during 2004-05 and
      analyzed for NO(3)(-) concentrations, delta(15)N(NO3), and delta(18)O(NO3).
      Samples from two forested watersheds indicated that NO(3)(-) derived from
      nitrification was dominant at baseflow. A watershed dominated by suburban land
      use had three delta(18)O(NO3) values greater than +25 per thousand, indicating a
      large direct contribution of atmospheric NO(3)(-) transported to the stream
      during some high flows. Two watersheds with large proportions of agricultural
      land use had many delta(15)N(NO3) values greater than +9 per thousand, suggesting
      an animal waste source consistent with regional dairy farming practices. These
      data showed a linear seasonal pattern with a delta(18)O(NO3):delta (15)N(NO3) of
      1:2, consistent with seasonally varying denitrification that peaked in late
      summer to early fall with the warmest temperatures and lowest annual streamflow.
      The large range of delta (15)N(NO3) values (10 per thousand) indicates that
      NO(3)(-) supply was likely not limiting the rate of denitrification, consistent
      with ground water and/or in-stream denitrification. Mixing of two or more
      distinct sources may have affected the seasonal isotope patterns observed in
      these two agricultural streams. In a mixed land use watershed of large drainage
      area, none of the source and process patterns observed in the small streams were
      evident. These results emphasize that observations at watersheds of a few to a
      few hundred km(2) may be necessary to adequately quantify the relative roles of
      various NO(3)(-) transport and process patterns that contribute to streamflow in
      large basins.

PMID- 19398513
TI  - Dissipation and leaching of acephate, chlorpyrifos, and their main metabolites in
      field soils of Malaysia.
AB  - Preventive treatment with insecticides at high dosing rates before planting of a
      new crop- soil drenching- is a common practice in some tropical intensive
      cropping systems, which may increase the risk of leaching, soil functioning, and
      pesticide uptake in the next crop. The degradation rates and migration of
      acephate and chlorpyrifos and their primary metabolites, methamidophos and 3,5,6
      trichloropyridinol (TCP), have been studied in clayey red yellow podzolic (Typic
      Paleudults), alluvial (Typic Udorthents), and red yellow podzolic soils (Typic
      Kandiudults) of Malaysia under field conditions. The initial concentrations of
      acephate and chlorpyrifos in topsoils were found to strongly depend on solar
      radiation. Both pesticides and their metabolites were detected in subsoils at the
      deepest sampling depth monitored (50 cm) and with maximum concentrations up to
      2.3 mg kg(-1) at soil depths of 10 to 20 cm. Extraordinary high dissipation rates
      for weakly sorbed acephate was in part attributed to preferential flow which was
      activated due to the high moisture content of the soils, high precipitation and
      the presence of conducting macropores running from below the A horizons to at
      least 1 m, as seen from a dye tracer experiment. Transport of chlorpyrifos and
      TCP which both sorb strongly to soil organic matter was attributed to macropore
      transport with soil particles. The half-lives for acephate in topsoils were 0.4
      to 2.6 d while substantially longer half-lives of between 12.6 and 19.8 d were
      observed for chlorpyrifos. The transport through preferential flow of strongly
      sorbed pesticides is of concern in the tropics.

PMID- 19398514
TI  - Use of mixed solvent systems to eliminate sorption of strongly hydrophobic
      organic chemicals on container walls.
AB  - Strongly hydrophobic organic chemicals (SHOCs) can be defined as neutral organic
      chemicals that have soil organic carbon (OC) normalized sorption coefficient
      (K(OC)) >10,000. Sorption isotherms of SHOCs are normally measured in aqueous
      systems to determine K(OC). Since SHOCs can adsorb on container walls leading to
      overestimation of K(OC), we used mixed solvent systems to characterize this
      potential error. Sorption coefficient (K(M)) and percent recovery (%R(M)) of
      anthracene, DDT, and dieldrin during sorption on centrifuge tubes made of
      polytetrafluoroethylene (PTFE), polycarbonate (PC), polypropylene copolymer
      (PPCO), and glass high pressure liquid chromatography vials (HPLCV) were measured
      in volume ratio-varied methanol-water mixtures until 100% recovery of the sorbate
      was achieved. The data were evaluated using the Solvophobic theory. The K(M)
      values of the entire test SHOCs decreased exponentially with increasing fraction
      of methanol (f(c)). For sorption on PTFE, 100% recovery of the three chemicals
      was at f(c) > 0.45. However, 100% recovery of DDT and anthracene from PC and PPCO
      was at f(c) > 0.90. The 100% recovery of dieldrin from HPLC vials was at f(c) >
      0.70. In water the calculated recoveries of DDT, dieldrin, and anthracene from
      PTFE were 32, 43, and 48%, respectively. However, the recoveries of dieldrin from
      HPLC vials and DDT and anthracene from PC and PPCO ranged from 2 to 14%. The data
      demonstrate that sorption on container walls is a source of error that can reduce
      the integrity of the analyte and might be one of the causes for the large
      variability in literature K(OC) values for SHOCs.

PMID- 19398515
TI  - Adsorption and degradation of ketoprofen in soils.
AB  - Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID), was commonly found in
      treated wastewater due to its incomplete removal during sewage treatment plant
      processes. As treated wastewater is increasingly used for landscape irrigation,
      it is imperative to understand the leaching potential for ketoprofen in receiving
      soils. In this study, adsorption and degradation experiments were conducted in
      four U.S. soils with different physicochemical characteristics. Ketoprofen was
      not strongly adsorbed to the four soils with K(d) values ranging from 1.26 to
      8.24 L kg(-1), suggesting its potential to move downward with percolating water.
      The adsorption was positively related to the soil organic matter (OM) content
      (R(2) = 0.890). Degradation experiment showed that half-lives (t(1/2)) of
      ketoprofen were 4.58 d in Arlington sandy loam (ASL, coarse-loamy, mixed, active,
      thermic Haplic Durixeralfs), 8.04 d in Hanford loamy sand (HLS, coarse-loamy,
      mixed, superactive, nonacid, thermic Typic Xerorthents), 15.37 d in Imperial
      silty clay (ISC, fine, semectitc, calcareous, hyperthermic Vertic Torrifluvents),
      and 27.61 d in Palouse silt loam (PSL) soil (fine-silty, mixed, superactive,
      mesic Pachic Ultic Haploxerolls), respectively. Degradation of ketoprofen in
      soils appeared to be influenced by the soil OM content. The prolonged t(1/2) by
      sterilization indicated that microbial degradation was the dominant pathway for
      ketoprofen degradation in soils, while photodegradation only contributed a small
      portion to the ketoprofen degradation. The t(1/2) and K(oc) values were fitted to
      screening models to predict the leaching potential of ketoprofen in soils. It
      appeared that relatively high leaching potential of ketoprofen existed in ISC and
      PSL soils.

PMID- 19398516
TI  - Impact of elevated copper on the rate and gaseous products of denitrification in
      freshwater sediments.
AB  - Application of Cu-containing algicides to water reservoirs for algal control
      leads to sediment Cu enrichment, but the impact of Cu accumulation on the NO(3)(
      )-attenuation capacity of these ecosystems is uncertain. With the knowledge that
      the reduction of N(2)O to N(2) is mediated by a Cu-dependent enzyme, it is
      hypothesized that an inverse variation exists between Cu availability and the
      mole fraction of N(2)O (F(N2O)) in denitrification products. A study was
      conducted to test this hypothesis and also to assess the impact of elevated Cu on
      nitrification and denitrification. Sediments were collected from areas untreated
      (NCT) and treated (CT) with the algicide cutrine (Cu ethanolamine) in three
      central Indiana reservoirs, and were assayed at both in situ Cu content and after
      amendment with CuSO(4). Results showed that Cu addition had a depressive, but
      short-lived effect on the processes investigated, with nitrification being most
      sensitive. Past cutrine treatments did not significantly affect either
      denitrification or F(N2O). However, a significant difference (P < 0.04) among
      reservoirs was found with respect to denitrification (Eagle Creek: 3.2; Geist:
      1.6 and Morse: 4.2 mg N kg(-1) h(-1)) and F(N2O) (0.51, 0.24, and 0.31,
      respectively). Negative relationships (r(2): 0.30-0.64) between F(N2O) and water
      extractable Cu were found only when the analysis was conducted separately for
      each reservoir, suggesting that Cu solubility is controlled by sediment
      properties specific to each reservoir. Overall, results of this study indicate
      that neither the NO(3)(-)-removal capacity of sediments nor the composition of
      denitrification N gases is affected by past treatments with cutrine.

PMID- 19398517
TI  - Managing tile drainage, subirrigation, and nitrogen fertilization to enhance crop
      yields and reduce nitrate loss.
AB  - Improving field-crop use of fertilizer nitrogen is essential for protecting water
      quality and increasing crop yields. The objective of this study was to determine
      the effectiveness of controlled tile drainage (CD) and controlled tile drainage
      with subsurface irrigation (CDS) for mitigating off-field nitrate losses and
      enhancing crop yields. The CD and CDS systems were compared on a clay loam soil
      to traditional unrestricted tile drainage (UTD) under a corn (Zea Mays L.)
      soybean (Glycine Max. (L.) Merr.) rotation at two nitrogen (N) fertilization
      rates (N1: 150 kg N ha(-1) applied to corn, no N applied to soybean; N2: 200 kg N
      ha(-1) applied to corn, 50 kg N ha(-1) applied to soybean). The N concentrations
      in tile flow events with the UTD treatment exceeded the provisional long-term
      aquatic life limit (LT-ALL) for freshwater (4.7 mg N L(-1)) 72% of the time at
      the N1 rate and 78% at the N2 rate, whereas only 24% of tile flow events at N1
      and 40% at N2 exceeded the LT-ALL for the CDS treatment. Exceedances in N
      concentration for surface runoff and tile drainage were greater during the
      growing season than the non-growing season. At the N1 rate, CD and CDS reduced
      average annual N losses via tile drainage by 44 and 66%, respectively, relative
      to UTD. At the N2 rate, the average annual decreases in N loss were 31 and 68%,
      respectively. Crop yields from CDS were increased by an average of 2.8% relative
      to UTD at the N2 rate but were reduced by an average of 6.5% at the N1 rate.
      Hence, CD and CDS were effective for reducing average nitrate losses in tile
      drainage, but CDS increased average crop yields only when additional N fertilizer
      was applied.

PMID- 19398518
TI  - Dissolved organic carbon losses from tile drained agroecosystems.
AB  - Artificial subsurface drainage is commonly used in midwestern agriculture and
      drainage losses of dissolved organic carbon (DOC) from such systems are an under
      quantified portion of the terrestrial carbon (C) cycle. The objectives of this
      study were to determine the effect of common agricultural management practices on
      DOC losses from subsurface tile drains and to assess patterns of loss as a
      function of year, time of year, and drainflow. Daily drainflow was collected
      across six water years (1999-2004) from a restored prairie grass system and
      cropping systems which include continuous corn (Zea mays L.) and corn-soybean
      [Glycine max (L.) Merr.] rotations fertilized with urea-ammonium-nitrate (UAN) or
      swine (Sus scrofa) manure lagoon effluent. The DOC concentrations in tile
      drainflow were low, typically <2 mg L(-1). Yearly DOC losses, which ranged from
      1.78 to 8.61 kg ha(-1), were not affected by management practices and were small
      compared to organic C inputs. Spring application of lagoon effluent increased
      yearly flow-weighted (FW)-DOC concentrations relative to other cropping systems
      in three of the years and increased monthly FW-DOC concentrations when drainflow
      occurred within 1 mo of application. Drainflow was significantly and positively
      correlated with DOC loss. Drainflow also affected DOC concentrations as greater 6
      yr cumulative drainflow was associated with lower 6-yr FW-DOC concentrations and
      greater daily drainflow was associated with higher daily DOC concentrations. Our
      results indicate that lagoon effluent application and fertilizer N rates do not
      affect long-term losses of DOC from tile drains and that drainflow is the main
      driver of DOC losses.

PMID- 19398519
TI  - Broiler litter application method and runoff timing effects on nutrient and
      Escherichia coli losses from tall fescue pasture.
AB  - The inability to incorporate manure into permanent pasture leads to the
      concentration of nutrients near the soil surface with the potential to be
      transported off site by runoff water. In this study, we used rainfall simulations
      to examine the effect of broiler chicken (Gallus gallus domesticus) litter
      application method and the runoff timing on nutrient and E. coli losses from tall
      fescue (Festuca arundinacea Schreb.) pasture on a Hartsells sandy loam soil (fine
      loamy, siliceous, subactive, thermic Typic Hapludults)) in Crossville, AL.
      Treatments included two methods of litter application (surface broadcast and
      subsurface banding), commercial fertilizer, and control. Litter was applied at a
      rate of 8.97 Mg ha(-1). Treatments were assigned to 48 plots with four blocks (12
      plots each) arranged in a randomized complete block design to include three
      replications in each block. Simulated rainfall was applied to treatments as
      follows: Day 1, block 1 (runoff 1); Day 8, block 2 (runoff 2); Day 15, block 3
      (runoff 3); and Day 22, block 4 (runoff 4). Total phosphorus (TP), inorganic N,
      and Escherichia coli concentrations in runoff from broadcast litter application
      were all significantly greater than from subsurface litter banding. The TP losses
      from broadcast litter applications averaged 6.8 times greater than those from
      subsurface litter applications. About 81% of the runoff TP was in the form of
      dissolved reactive phosphorus (DRP) for both litter-application methods. The
      average losses of NO(3)-N and total suspended solids (TSS) from subsurface
      banding plots were 160 g ha(-1) and 22 kg ha(-1) compared to 445 g ha(-1) and 69
      kg ha(-1) for the broadcast method, respectively. Increasing the time between
      litter application and the first runoff event helped decrease nutrient and E.
      coli losses from surface broadcast litter, but those losses generally remained
      significantly greater than controls and subsurface banded, regardless of runoff
      timing. This study shows that subsurface litter banding into perennial grassland
      can substantially reduce nutrient and pathogen losses in runoff compared to the
      traditional surface-broadcast practice.

PMID- 19398520
TI  - Factors influencing the persistence of fecal Bacteroides in stream water.
AB  - Laboratory microcosm experiments were used to assess the effects of environmental
      parameters on the persistence of the Bacteroides 16S rRNA genes derived from
      equine fecal samples in stream water to investigate the utility of Bacteroides
      spp. as fecal indicator organisms. Quantitative real-time polymerase chain
      reaction (qPCR) was used to measure gene concentrations over time with treatments
      designed to compare filtered vs. unfiltered stream water, fecal aggregate size,
      initial fecal concentrations, and water temperatures. Comparison of
      Bacteroides16S rRNA genes/mL in microcosms constructed with unfiltered stream
      water and filtered stream water indicated that stream water filtration to remove
      indigenous microorganisms followed by temperature had the largest effects on gene
      persistence. First-order exponential decay functions were fitted to the data from
      each microcosm constructed using unfiltered stream water, and the decay constants
      (k) ranged from 0.0071 h(-1) in the microcosms incubated at 5 degrees C to 0.0336
      h(-1) in a set of microcosms incubated at 25 degrees C. Analysis of k calculated
      from the 10 experimental treatments indicated that k is more highly correlated to
      temperature than initial Bacteroides 16S rRNA gene starting concentrations. The
      equation resulting from graphing k (as the dependent variable) vs. temperature
      (as the independent variable) best fit a peak, Gaussian, 3 parameter function
      with a maximum decay at 30 degrees C, a r(2) of 0.83 and all parameters were
      significant (P < 0.0015). Thus this data suggest that factors that reduce
      biological activity, such as physical removal of stream microorganisms by
      filtration and low temperature, result in slower Bacteroides 16S rRNA gene decay.

PMID- 19398521
TI  - Storm water pollutant removal performance of compost filter socks.
AB  - In 2005, the U.S. Environmental Protection Agency (USEPA) National Menu of Best
      Management Practices (BMPs) listed compost filter socks (FS) as an approved BMP
      for controlling sediment in storm runoff on construction sites. The objectives of
      this study were to determine if FS with or without the addition of a flocculation
      agent to the FS system can significantly remove (i) suspended clay and silt
      particulates, (ii) ammonium nitrogen (NH(4)-N) and nitrate-nitrite nitrogen
      (NO(3)-N), (iii) fecal bacteria, (iv) heavy metals, and (v) petroleum
      hydrocarbons from storm water runoff. Five separate (I-V) 30-min simulated
      rainfall-runoff events were applied to soil chambers packed with Hartboro silt
      loam (fine-loamy, mixed, active, nonacid, mesic fluvaquentic Endoaquepts) or a 6
      mm concrete veneer on a 10% slope, and all runoff was collected and analyzed for
      hydraulic flow rate, volume, pollutant concentrations, pollutant loads, and
      removal efficiencies. In corresponding experiments, runoff was analyzed for (i)
      size of sediment particles, (ii) NH(4)-N and NO(3)-N, (iii) total coliforms (TC)
      and Escherichia coli, (iv) Cd, Cr, Cu, Ni, Pb and Zn, and (v) gasoline, diesel,
      and motor oil, respectively. Results showed that: (i) FS removed 65% and 66% of
      clay (<0.002 mm) and silt (0.002-0.05 mm), respectively; (ii) FS removed 17%, and
      11% of NH(4)-N and NO(3)-N, respectively and when NitroLoxx was added to the FS,
      removal of NH(4)-N load increased to 27%; (iii) total coliform and E. coli
      removal efficiencies were 74 and 75%, respectively, however, when BactoLoxx was
      added, removal efficiency increased to 87 and 99% for TC and 89 and 99% for E.
      coli, respectively; (iv) FS removal efficiency for Cd, Cr, Cu, Ni, Pb, and Zn
      ranged from 37 to 72%, and, when MetalLoxx was added, removal efficiency ranged
      from 47 to 74%; and (v) FS removal efficiency for the three petroleum
      hydrocarbons ranged from 43 to 99% and the addition of PetroLoxx increased motor
      oil and gasoline removal efficiency in the FS system.

PMID- 19398522
TI  - Interactions of tillage and cover crop on water, sediment, and pre-emergence
      herbicide loss in glyphosate-resistant cotton: implications for the control of
      glyphosate-resistant weed biotypes.
AB  - The need to control glyphosate [N-(phosphonomethyl)glycine]-resistant weed
      biotypes with tillage and preemergence herbicides in glyphosate-resistant crops
      (GRCs) is causing a reduction in no-tillage hectarage thereby threatening the
      advances made in water quality over the past decade. Consequently, if
      environmental gains afforded by GRCs are to be maintained, then an in-field best
      management practice (BMP) compatible with tillage is required for hectarage
      infested with glyphosate-resistant weed biotypes. Thus, 1 d after a preemergent
      application of fluometuron [N,N-dimethyl-N'-(3-(trifluoromethyl)phenyl)urea]
      (1.02 kg ha(-1)) and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2
      methoxy-1-methylethyl)acetamide] (1.18 kg ha(-1)) to a Dundee silt loam (fine
      silty, mixed, active, thermic Typic Endoaqualf), simulated rainfall (60 mm h(-1))
      was applied to 0.0002-ha microplots for approximately 1.25 h to elucidate tillage
      (no tillage [NT] and reduced tillage [RT])and cover crop (no cover [NC] and rye
      cover [RC]) effects on water, sediment, and herbicide loss in surface runoff.
      Regardless of tillage, RC delayed time-to-runoff 1.3-fold, reduced cumulative
      runoff volume 1.4-fold, and decreased cumulative sediment loss 4.7-fold.
      Cumulative fluometuron loss was not affected by tillage or cover crop.
      Conversely, total metolachlor loss was 1.3-fold lower in NT than RT and 1.4-fold
      lower in RC than NC. These data indicate that RC can be established in hectarage
      requiring tillage and potentially curtail water, sediment, and preemergence
      herbicide losses in the spring to levels equivalent to or better than that of NT,
      thereby protecting environmental gains provided by GRCs.

PMID- 19398523
TI  - Large-scale performance and design for construction activity erosion control best
      management practices.
AB  - The National Pollutant Discharge Elimination System (NPDES) Phase II requires
      construction activities to have erosion and sediment control best management
      practices (BMPs) designed and installed for site storm water management. Although
      BMPs are specified on storm water pollution prevention plans (SWPPPs) as part of
      the construction general permit (GP), there is little evidence in the research
      literature as to how BMPs perform or should be designed. The objectives of this
      study were to: (i) comparatively evaluate the performance of common construction
      activity erosion control BMPs under a standardized test method, (ii) evaluate the
      performance of compost erosion control blanket thickness, (iii) evaluate the
      performance of compost erosion control blankets (CECBs) on a variety of slope
      angles, and (iv) determine Universal Soil Loss Equation (USLE) cover management
      factors (C factors) for these BMPs to assist site designers and engineers. Twenty
      three erosion control BMPs were evaluated using American Society of Testing and
      Materials (ASTM) D-6459, standard test method for determination of ECB
      performance in protecting hill slopes from rainfall induced erosion, on 4:1
      (H:V), 3:1, and 2:1 slopes. Soil loss reduction for treatments exposed to 5 cm of
      rainfall on a 2:1 slope ranged from-7 to 99%. For rainfall exposure of 10 cm,
      treatment soil loss reduction ranged from 8 to 99%. The 2.5 and 5 cm CECBs
      significantly reduced erosion on slopes up to 2:1, while CECBs < 2.5 cm are not
      recommended on slopes >or= 4:1 when rainfall totals reach 5 cm. Based on the soil
      loss results, USLE C factors ranged from 0.01 to 0.9. These performance and
      design criteria should aid site planners and designers in decision-making
      processes.

PMID- 19398524
TI  - Sediment contamination and faunal communities in two subwatersheds of Mona Lake,
      Michigan.
AB  - Urbanization of watersheds can impose multiple stressors on stream, wetland, and
      lake ecosystems. Sediment contamination, alterations to the natural hydrologic
      regime, and nutrient loading are examples of these stressors which often occur
      simultaneously. As a consequence, restoration is challenged by the multi-stressor
      reality of most urban watersheds. The goal of this study was to compare two
      watersheds in western Michigan, both with substantial urban development, but with
      different levels of sediment contamination resulting from historic industrial
      activities, to determine the effects of contamination on invertebrate and fish
      community structure. The study included multiple sites on both streams, two
      wetlands adjacent to each stream, and the embayments where each stream emptied
      into Mona Lake. We compared a suite of abiotic parameters including sediment
      contamination, sediment toxicity, and water column chemical/physical conditions
      as well as fish and invertebrate community structure. Sediment contaminants,
      including heavy metals and polycyclic aromatic hydrocarbons, were found in higher
      concentrations and survival of test organisms in toxicity bioassays was reduced
      in the more industrialized watershed. Fewer insect taxa, especially the sensitive
      Ephemeroptera, Plecoptera, and Trichoptera, were found in the more industrialized
      system. Fish taxa richness and catch per unit effort were reduced in the wetlands
      of the more industrialized watershed as well and both invertebrate and fish index
      of biotic integrity scores were also lower in the more industrialized system. Our
      study demonstrates that contamination due to historic industrial activities can
      have substantial and lasting effects on biotic communities of multiple habitat
      types well downstream of where the activities occurred.

PMID- 19398525
TI  - Salinity and sodicity of weathered minesoils in northwestern new Mexico and
      northeastern Arizona.
AB  - Evolving relationships between electrical conductivity (EC) and sodium adsorption
      ratio (SAR) in reconstructed soils at surface mines have been insufficiently
      documented in the literature. Some minesoils (i.e., rootzone material) are
      classified as saline, sodic, or saline-sodic and are considered unsuitable for
      revegetation. Weatherable minerals such as calcite and gypsum are common in
      alkaline minesoils and on dissolution tend to mitigate elevated SAR levels by
      maintaining or increasing electrolytes in the soil and providing sources of
      exchangeable calcium and magnesium. Topsoils (i.e., coversoils) contribute to
      mitigation of sodic conditions when soluble cations are translocated from
      coversoils into the underlying minesoils. This study evaluated the weathering
      characteristics of minesoils sites from three surface coal mines in northwestern
      New Mexico and northeastern Arizona. Minesoils were grouped into 11 classes based
      on EC and SAR. After 6 to 14 yr, differences between upper and lower halves of
      the coversoils suggest general increases occurred with EC, SAR, chloride (Cl(-)),
      and sulfate (SO(4)(2-)) with depth. Within the reclaimed minesoils, there were
      several significant (P < 0.05 or < 0.10) relationships among EC and SAR that
      related to Minesoil Class. Lower SAR levels with corresponding increases in EC
      compared to baseline minesoils were more apparent in upper minesoil depths (0-5
      and 5-15 cm). Minesoil anion concentrations suggested coversoil leachates and
      gypsum dissolution influenced EC and SAR chemistry. Over time, chemical changes
      have increased the apparent stability of the saline and sodic reclaimed minesoils
      studied thereby reducing risks associated with potential aggregate slaking and
      clay particle dispersion.

PMID- 19398526
TI  - Simulation of pharmaceutical and personal care product transport to tile drains
      after biosolids application.
AB  - Pharmaceuticals and personal care products (PPCPs) carried in biosolids may reach
      surface waters or ground water when these materials are applied as fertilizer to
      agricultural land. During preferential flow conditions created by land
      application of liquid municipal biosolids (LMB), the residence time of solutes in
      the macropores may be too short for sorption equilibration. The physically based
      dual-permeability model MACRO is used in environmental risk assessments for
      pesticides and may have potential as an environmental risk assessment tool for
      PPCPs. The objective of this study was to evaluate MACRO and an updated version
      of MACRO that included non-equilibrium sorption in macropores using data from
      experiments conducted in eastern Ontario, Canada on the transport of three PPCPs
      (atenolol, carbamazepine, and triclosan), the nicotine metabolite cotinine, and
      the strongly sorbing dye rhodamine WT applied in LMB. Results showed that the
      MACRO model could not reproduce the measured rhodamine WT concentrations (Nash
      Sutcliffe coefficient [NS] for the best simulation = -0.057) in drain discharge.
      The updated version resulted in better fits to measured data for PPCP (average NS
      = 0.97) and rhodamine WT (NS = 0.84) concentrations. However, it was not possible
      to simulate all compounds using the same set of hydraulic parameters, which
      indicates that the model does not fully account for all relevant processes. The
      results presented herein show that non-equilibrium sorption in macropores has a
      large impact on simulated solute transport for reactive compounds contained in
      LMB. This process should be considered in solute transport models that are used
      for environmental risk assessments for such compounds.

PMID- 19398527
TI  - Soil nitrogen balance under wastewater management: field measurements and
      simulation results.
AB  - The use of treated wastewater for irrigation of crops could result in high
      nitrate-nitrogen (NO(3)-N) concentrations in the vadose zone and ground water.
      The goal of this 2-yr field-monitoring study in the deep silty clay loam soils
      south of Dodge City, Kansas, was to assess how and under what circumstances N
      from the secondary-treated, wastewater-irrigated corn reached the deep (20-45 m)
      water table of the underlying High Plains aquifer and what could be done to
      minimize this problem. We collected 15.2-m-deep soil cores for characterization
      of physical and chemical properties; installed neutron probe access tubes to
      measure soil-water content and suction lysimeters to sample soil water
      periodically; sampled monitoring, irrigation, and domestic wells in the area; and
      obtained climatic, crop, irrigation, and N application rate records for two
      wastewater-irrigated study sites. These data and additional information were used
      to run the Root Zone Water Quality Model to identify key parameters and processes
      that influence N losses in the study area. We demonstrated that NO(3)-N transport
      processes result in significant accumulations of N in the vadose zone and that
      NO(3)-N in the underlying ground water is increasing with time. Root Zone Water
      Quality Model simulations for two wastewater-irrigated study sites indicated that
      reducing levels of corn N fertilization by more than half to 170 kg ha(-1)
      substantially increases N-use efficiency and achieves near-maximum crop yield.
      Combining such measures with a crop rotation that includes alfalfa should further
      reduce the accumulation and downward movement of NO(3)-N in the soil profile.

PMID- 19398528
TI  - On the adsorption of tetracycline by calcined magnesium-aluminum hydrotalcites.
AB  - Exploiting effective sorbents for antibiotic adsorption is highly desirable for
      the elimination of ecological risks from antibiotic contamination. In this study,
      MgAl-CO(3)(2-) hydrotalcites with different Mg/Al molar ratios were prepared and
      tetracycline (TC) adsorption to the hydrotalcites and calcined hydrotalcites was
      investigated by batch experiments. Calcined hydrotalcites had higher adsorption
      capacities compared to MgAl-CO(3)(2-) hydrotalcites. At low TC equilibrium
      concentrations, calcined hydrotalcites with differing Mg/Al ratios showed
      approximately identical TC uptakes. However, at high tetracycline concentration,
      greater TC adsorption capacity was observed for calcined hydrotalcite having a
      high Mg/Al ratio (i.e., 4.4). X-ray diffraction (XRD) characterization showed the
      presence of Mg-Al oxide solid solution in TC -loaded calcined hydrotalcite,
      suggesting that suspension of the calcined product in water and adsorption of TC
      had led to only partial reconstruction of the layered structure. We hypothesize
      that TC was adsorbed on the MgO surface at high equilibrium concentrations. The
      behavior of TC adsorption on the calcined hydrotalcite was well described by a
      dual adsorption model. Kinetic analysis suggested that at low adsorption levels,
      TC adsorption by calcined hydrotalcite could be modeled by both a pseudo second
      order kinetics model and a nucleation-growth model. The present work demonstrates
      that calcined hydrotalcites may be promising adsorbents for effective removal of
      TC from water resources.

PMID- 19398530
TI  - Exporting large volumes of municipal sewage sludge through turfgrass sod
      production.
AB  - The nutrient content of sludge produced by municipal water treatment works often
      far exceeds the requirements of nearby crops. Transporting sludge further afield
      is not always economically viable. This study reports on the potential to export
      large volumes of anaerobically digested municipal sewage sludge through turfgrass
      sod production. Hypotheses examined are that sludge loading rates far above
      recommendations based on crop nutrient removal (i) are possible without reducing
      turf growth and quality, (ii) do not cause an accumulation of N and P below the
      active root zone, (iii) can minimize soil loss through sod harvesting, and (iv)
      do not cause unacceptably high nitrate and salt leaching. An 8 Mg ha(-1) sludge
      control (the recommended limit) was compared with sludge rates of 0, 33, 67, and
      100 Mg ha(-1) on a loamy, kaolinitic, mesic, Typic Eutrustox soil near
      Johannesburg, South Africa. Sludge application rates up to 67 Mg ha(-1)
      significantly improved turfgrass establishment rate and color. The ability of
      sods to remain intact during handling and transport improved as the sludge
      application rate increased to 33 Mg ha(-1) but deteriorated at higher rates. A
      sludge application rate of 100 Mg ha(-1) was needed to eliminate soil loss, but
      this rate was associated with unacceptably high N leaching losses. All our
      hypotheses were accepted for application rates not exceeding 33 Mg ha(-1) on the
      proviso that some soil loss was acceptable and that the leaching fraction was
      carefully managed during the first 2 mo after sludge application.

PMID- 19398529
TI  - Greenhouse gas microbiology in wet and dry straw crust covering pig slurry.
AB  - Liquid manure (slurry) storages are sources of gases such as ammonia (NH(3)) and
      methane (CH(4)). Danish slurry storages are required to be covered to reduce
      NH(3) emissions and often a floating crust of straw is applied. This study
      investigated whether physical properties of the crust or crust microbiology had
      an effect on the emission of the potent greenhouse gases CH(4) and nitrous oxide
      (N(2)O) when crust moisture was manipulated ("dry", "moderate", and "wet"). The
      dry crust had the deepest oxygen penetration (45 mm as compared to 20 mm in the
      wet treatment) as measured with microsensors, the highest amounts of nitrogen
      oxides (NO(2)(-) and NO(3)(-)) (up to 36 mumol g(-1) wet weight) and the highest
      emissions of N(2)O and CH(4). Fluorescent in situ hybridization and gene-specific
      polymerase chain reaction (PCR) were used to detect occurrence of bacterial
      groups. Ammonia-oxidizing bacteria (AOB) were abundant in all three crust types,
      whereas nitrite-oxidizing bacteria (NOB) were undetectable and methane-oxidizing
      bacteria (MOB) were only sparsely present in the wet treatment. A change to
      anoxia did not affect the CH(4) emission indicating the virtual absence of
      aerobic methane oxidation in the investigated 2-mo old crusts. However, an
      increase in N(2)O emission was observed in all crusted treatments exposed to
      anoxia, and this was probably a result of denitrification based on NO(x)(-) that
      had accumulated in the crust during oxic conditions. To reduce overall greenhouse
      gas emissions, floating crust should be managed to optimize conditions for
      methanotrophs.

PMID- 19398533
TI  - Auditory, visual, and auditory-visual perception of emotions by individuals with
      cochlear implants, hearing AIDS, and normal hearing.
AB  - This study evaluated the benefits of cochlear implant (CI) with regard to emotion
      perception of participants differing in their age of implantation, in comparison
      to hearing aid users and adolescents with normal hearing (NH). Emotion perception
      was examined by having the participants identify happiness, anger, surprise,
      sadness, fear, and disgust. The emotional content was placed upon the same
      neutral sentence. The stimuli were presented in auditory, visual, and combined
      auditory-visual modes. The results revealed better auditory identification by the
      participants with NH in comparison to all groups of participants with hearing
      loss (HL). No differences were found among the groups with HL in each of the 3
      modes. Although auditory-visual perception was better than visual-only perception
      for the participants with NH, no such differentiation was found among the
      participants with HL. The results question the efficiency of some currently used
      CIs in providing the acoustic cues required to identify the speaker's emotional
      state.

PMID- 19398534
TI  - Telehealth and the deaf: a comparison study.
AB  - Within the deaf population, an extreme mental health professional shortage exists
      that may be alleviated with videoconferencing technology-also known as
      telehealth. Moreover, much needed mental health education within the deaf
      population remains largely inaccessible. Researchers have warned that the deaf
      population may remain underserved if significant changes do not take place with
      traditional service delivery methods. This article evaluated the efficacy of
      telehealth in teaching psychoeducational objectives, with special emphasis given
      to its application to the deaf population. Results indicate that telehealth can
      be regarded as an efficacious and cost-effective option in delivering health care
      to the deaf population. Participants also indicated satisfaction with the
      telehealth technology. The use of printed transcripts for educational purposes is
      encouraged given the significant findings in this article. The findings also have
      implications for the literature on single-session interventions.

PMID- 19398535
TI  - Activation switch in the transmembrane domain of metabotropic glutamate receptor.
AB  - Metabotropic glutamate receptors (mGluRs), members of family 3 G protein-coupled
      receptors, play pivotal roles in the modulation of synaptic transmission and are
      important drug targets for various neurological diseases. The structures of the
      extracellular ligand-binding domain (ECD) of mGluRs and its changes upon ligand
      binding have been well studied by various techniques, including X-ray
      crystallography. In contrast, little is known about the structure and structural
      changes of the seven-transmembrane domain (TMD). Here we searched for
      constitutively active mutation (CAM) sites in the TMD of mGluR8 to get insight
      into the epicenter of the structural changes in TMD, a potential target for
      allosteric ligands. Mutational analyses based on the knowledge of activating
      mutations of calcium-sensing receptor showed the presence of several CAM sites in
      the TMD of mGluR8. Among them, the site at position 764 in helix V, where
      threonine is present, is unique in that any substitution resulted in elevation of
      the basal activity, and some substitutions caused a loss of responsiveness to
      agonist. Further comprehensive mutational analyses indicated that the additional
      mutation of the CAM site at position 663 in helix III, where a tyrosine residue
      is present, generated a revertant phenotype. Mutations at these sites also
      increased the agonist binding affinity, although these sites are far from the
      ECD. These results indicated that the specific pair of amino acids at these CAM
      sites forms an activation switch that stabilizes the inactive state of mGluR8 and
      mediates the signal flow from the ECD to the cytoplasmic G protein-interacting
      site.

PMID- 19398536
TI  - Maternal responses to adolescent positive affect are associated with adolescents'
      reward neuroanatomy.
AB  - The development of reward-based learning and decision-making, and the neural
      circuitry underlying these processes, appears to be influenced negatively by
      adverse child-rearing environments characterized by abuse and other forms of
      maltreatment. No research to-date has investigated whether normative variations
      in the child-rearing environment have effects on adolescent brain structure. We
      examined whether normative variations in maternal responses to adolescents'
      positive affective behavior were associated with morphometric measures of the
      adolescents' affective neural circuitry, namely the amygdala, orbitofrontal
      cortex (OFC), and anterior cingulate cortex (ACC). Healthy adolescents (N = 113)
      participated in laboratory-based interaction tasks with their mothers, and
      underwent high-resolution (3T) structural magnetic resonance imaging (MRI). The
      mother-adolescent interactions included a pleasant event-planning interaction
      (EPI) and a conflictual problem-solving interaction (PSI). Adolescents, whose
      mothers displayed more punishing responses to their positive affective behavior
      during both tasks, and only during the PSI, had larger left dorsal ACC and
      bilateral OFC volumes, respectively. In addition, boys whose mothers evidenced
      this pattern of behavior during the EPI had larger right amygdala volumes. These
      results suggest that normative variations in maternal responses to affective
      behavior are associated with the structural characteristics of adolescents'
      affective neural circuitry, which may have implications for the development of
      their social, cognitive and affective functioning.

PMID- 19398537
TI  - Emotion regulation in spider phobia: role of the medial prefrontal cortex.
AB  - Phobic responses are strong emotional reactions towards phobic objects, which can
      be described as a deficit in the automatic regulation of emotions. Difficulties
      in the voluntary cognitive control of these emotions suggest a further phobia
      specific deficit in effortful emotion regulation mechanisms. The actual study is
      based on this emotion regulation conceptualization of specific phobias. The aim
      is to investigate the neural correlates of these two emotion regulation deficits
      in spider phobics. Sixteen spider phobic females participated in a functional
      magnetic resonance imaging (fMRI) study in which they were asked to voluntarily
      up- and down-regulate their emotions elicited by spider and generally aversive
      pictures with a reappraisal strategy. In line with the hypothesis concerning an
      automatic emotion regulation deficit, increased activity in the insula and
      reduced activity in the ventromedial prefrontal cortex was observed. Furthermore,
      phobia-specific effortful regulation within phobics was associated with altered
      activity in medial prefrontal cortex areas. Altogether, these results suggest
      that spider phobic subjects are indeed characterized by a deficit in the
      automatic as well as the effortful regulation of emotions elicited by phobic
      compared with aversive stimuli. These two forms of phobic emotion regulation
      deficits are associated with altered activity in different medial prefrontal
      cortex subregions.

PMID- 19398538
TI  - OspC-independent infection and dissemination by host-adapted Borrelia
      burgdorferi.
AB  - Borrelia burgdorferi OspC is required for the spirochete to establish infection
      in a mammal by tick transmission or needle inoculation. After a brief essential
      period, the protein no longer is required and the gene can be shut off. Using a
      system in which spirochetes contain only an unstable wild-type copy of the ospC
      gene, we can obtain mice persistently infected with bacteria lacking OspC. We
      implanted pieces of infected mouse skin subcutaneously in naive mice, using
      donors carrying wild-type or ospC mutant spirochetes, and found that both could
      infect mice by this method, with similar numbers of wild-type or ospC mutant
      spirochetes disseminated throughout the tissues of recipient mice. Recipient
      mouse immune responses to tissue transfer-mediated infection with wild-type or
      ospC mutant spirochetes were similar. These experiments demonstrate that
      mammalian host-adapted spirochetes can infect and disseminate in mice in the
      absence of OspC, thereby circumventing this hallmark of tick-derived or in vitro
      grown spirochetes. We propose a model in which OspC is one of a succession of
      functionally equivalent, essential proteins that are synthesized at different
      stages of mammalian infection. In this model, another protein uniquely present on
      host-adapted spirochetes performs the same essential function initially fulfilled
      by OspC. The strict temporal control of B. burgdorferi outer surface protein gene
      expression may reflect immunological constraints rather than distinct functions.

PMID- 19398539
TI  - Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein
      activates dendritic cells and induces a Th1 polarization.
AB  - Paratuberculosis is a chronic infectious disorder and a major problem in farmed
      ruminants. This disease is caused by Mycobacterium avium subsp. paratuberculosis.
      M. avium subsp. paratuberculosis is an important pathogen that causes Johne's
      disease in animals and also has been implicated as a possible cause of Crohn's
      disease in humans, but little is known about the protective immune responses to
      this microorganism. Fibronectin attachment protein (FAP) is a member of a family
      of fibronectin-binding proteins produced by several species of mycobacteria which
      is important in the pathogenesis of M. avium. Addition of recombinant FAP to
      human respiratory tract organ cultures inhibits M. avium binding to areas where
      there is epithelial damage. We characterized the role of FAP in promoting
      adaptive and innate immune responses. FAP functionally activated dendritic cells
      by augmenting the expression of CD80, CD86, major histocompatibility complex
      class I, and major histocompatibility complex class II. Moreover, FAP induced the
      allogeneic immunostimulatory capacity of dendritic cells by stimulating dendritic
      cell production of Th1-promoting interleukin-12. FAP also increased the
      production of gamma interferon by T cells in mixed-lymphocyte reactions, which
      would be expected to contribute to the Th1 polarization of the immune response.
      The expression of surface markers and cytokine production in dendritic cells was
      mediated by both mitogen-activated protein kinases and NF-kappaB pathways. These
      results show that FAP modulates the adaptive immune responses to M. avium subsp.
      paratuberculosis by inducing maturation and activation of dendritic cells, which
      drives Th1 polarization.

PMID- 19398541
TI  - Complementation of the fadA mutation in Fusobacterium nucleatum demonstrates that
      the surface-exposed adhesin promotes cellular invasion and placental
      colonization.
AB  - Fusobacterium nucleatum is a gram-negative oral anaerobe implicated in
      periodontal disease and adverse pregnancy outcome. The organism colonizes the
      mouse placenta, causing localized infection and inflammation. The mechanism of
      placental colonization has not been elucidated. Previous studies identified a
      novel adhesin from F. nucleatum, FadA, as being involved in the attachment and
      invasion of host cells. The fadA deletion mutant F. nucleatum 12230 US1 was
      defective in host cell attachment and invasion in vitro, but it also exhibited
      pleiotropic effects with altered cell morphology and growth rate. In this study,
      a fadA-complementing clone, F. nucleatum 12230 USF81, was constructed. The
      expression of FadA on USF81 was confirmed by Western blotting and
      immunofluorescent labeling. USF81 restored host cell attachment and invasion
      activities. The ability of F. nucleatum 12230, US1, and USF81 to colonize the
      mouse placenta was examined. US1 was severely defective in placental colonization
      compared to the wild type and USF81. Thus, FadA plays an important role in F.
      nucleatum colonization in vivo. These results also represent the first
      complementation studies for F. nucleatum. FadA may be a therapeutic target for
      preventing F. nucleatum colonization of the host.

PMID- 19398540
TI  - Borrelia burgdorferi RevA antigen binds host fibronectin.
AB  - Borrelia burgdorferi, the Lyme disease-causing spirochete, can persistently
      infect its vertebrate hosts for years. B. burgdorferi is often found associated
      with host connective tissue, where it interacts with components of the
      extracellular matrix, including fibronectin. Some years ago, a borrelial surface
      protein, named BBK32, was identified as a fibronectin-binding protein. However,
      B. burgdorferi BBK32 mutants are still able to bind fibronectin, indicating that
      the spirochete possesses additional mechanisms for adherence to fibronectin. We
      now demonstrate that RevA, an unrelated B. burgdorferi outer surface protein,
      binds mammalian fibronectin in a saturable manner. Site-directed mutagenesis
      studies identified the amino terminus of the RevA protein as being required for
      adhesion to fibronectin. RevA bound to the amino-terminal region of fibronectin.
      RevA binding to fibronectin was not inhibited by salt or heparin, suggesting that
      adhesin-ligand interactions are primarily nonionic and occur through the non
      heparin-binding regions of the fibronectin amino-terminal domains. revA genes are
      widely distributed among Lyme disease spirochetes, and the present studies
      determined that all RevA alleles tested bound fibronectin. In addition, RevB, a
      paralogous protein found in a subset of B. burgdorferi strains, also bound
      fibronectin. We also confirmed that RevA is produced during mammalian infection
      but not during colonization of vector ticks and determined that revA
      transcription is controlled through a mechanism distinct from that of BBK32.

PMID- 19398542
TI  - Distinct roles of CD28- and CD40 ligand-mediated costimulation in the development
      of protective immunity and pathology during Chlamydia muridarum urogenital
      infection in mice.
AB  - Infection with Chlamydia muridarum in the mouse urogenital tract can induce both
      protective immunity and inflammatory pathologies, which has been used as a model
      for understanding the immune and pathogenic mechanisms of C. trachomatis
      infection. We compared the roles of CD28- and CD40 ligand (CD40L)-mediated
      costimulation in C. muridarum infection. Mice with CD28 or CD80/CD86 gene
      knockout (KO) displayed an infection course similar to that of wild-type mice
      during both primary and secondary infection, suggesting that CD28-mediated
      costimulation is not required for protection against C. muridarum infection.
      However, mice deficient in CD40L or CD40 displayed a prolonged infection course
      after primary or secondary infection, suggesting that CD40-CD40L costimulation
      plays an essential role in the development of anti-C. muridarum immunity.
      Interestingly, the CD28- or CD80/CD86-deficient mice displayed significantly
      lower levels of inflammatory pathologies in the upper genital tracts after
      primary infection, although the attenuation in inflammation was no longer
      significant during secondary infection. However, the CD40L or CD40 KO mice
      developed inflammatory pathologies as severe as those in wild-type mice following
      either primary or secondary infection despite the obvious deficits in adaptive
      immunity in these KO mice. The resistance of CD28 or CD80/CD86 KO mice to
      chlamydial infection correlated with production of gamma interferon, while the
      development of inflammatory pathologies in CD40L or CD40 KO mice correlated with
      the production of other proinflammatory cytokines in mouse urogenital tracts
      during the early stages of the infection. These observations together suggest
      that C. muridarum-induced protective immunity and inflammatory pathologies can be
      mediated by distinct costimulatory signals.

PMID- 19398543
TI  - Chlamydial heat shock protein 60 induces acute pulmonary inflammation in mice via
      the Toll-like receptor 4- and MyD88-dependent pathway.
AB  - Heat shock protein 60 derived from Chlamydia pneumoniae (cHSP60) activates Toll
      like receptor 4 (TLR4) signaling through the MyD88 pathway in vitro, but it is
      not known how cHSP60 contributes to C. pneumoniae-induced lung inflammation. We
      treated wild-type (WT), TLR2(-/-), TLR4(-/-), or MyD88(-/-) mice intratracheally
      (i.t.) with recombinant cHSP60 (50 microg), UV-killed C. pneumoniae (UVCP; 5 x
      10(6) inclusion-forming units/mouse), lipopolysaccharide (2 microg), or phosphate
      buffered saline (PBS) and sacrificed mice 24 h later. Bronchoalveolar lavage
      (BAL) was obtained to measure cell counts and cytokine levels, lungs were
      analyzed for histopathology, and lung homogenate chemokine concentrations were
      determined. Bone marrow-derived dendritic cells (BMDDCs) were generated and
      stimulated with live C. pneumoniae (multiplicity of infection [MOI], 5), UVCP
      (MOI, 5), or cHSP60 for 24 h, and the expression of costimulatory molecules (CD80
      and CD86) was measured by fluorescence-activated cell sorting. cHSP60 induced
      acute lung inflammation with the same intensity as that of UVCP-induced
      inflammation in WT mice but not in TLR4(-/-) or MyD88(-/-) mice. cHSP60- and UVCP
      induced lung inflammation was associated with increased numbers of cells in BAL,
      increased neutrophil recruitment, and elevated BAL interleukin-6 (IL-6) levels.
      Both cHSP60 and UVCP induced IL-6 release and CD80 and CD86 expression in WT
      cells but not in MyD88(-/-) BMDDCs. cHSP60 stimulated DC activation in a TLR4-
      and MyD88-dependent manner with an intensity similar to that induced by UVCP.
      These data suggest that cHSP60 promotes lung inflammation and DC activation via
      TLR4 and MyD88 and therefore may play a significant role in the pathogenesis of
      C. pneumoniae-induced chronic inflammatory lung diseases.

PMID- 19398544
TI  - Bivalent recombinant vaccine for botulinum neurotoxin types A and B based on a
      polypeptide comprising their effector and translocation domains that is
      protective against the predominant A and B subtypes.
AB  - The botulinum neurotoxins (BoNTs) are a large family of extremely potent,
      neuroparalytic, dichain proteins which act at the peripheral nervous system. The
      wide genetic diversity observed with this neurotoxin family poses a significant
      challenge for the development of an effective botulinum vaccine. The present
      study describes a vaccine development platform based on protein fragments
      representing the N-terminal two-thirds of each toxin molecule. These fragments,
      designated LH(N), comprise the light chain and translocation domains of each
      neurotoxin and are devoid of any neuron-binding activity. Using codon-optimized
      genes, LH(N) fragments derived from BoNT serotypes A and B were expressed in
      Escherichia coli in high yield with >1 g of purified, soluble fragment
      recoverable from 4.5 liter-scale fermentations. The protective efficacy of
      LH(N)/A was significantly enhanced by treatment with formaldehyde, which induced
      intramolecular cross-linking but virtually no aggregation of the fragment. A
      single immunization of the modified fragment protected mice from challenge with a
      10(3) 50% lethal dose (LD(50)) of BoNT/A(1) with an 50% effective dose (ED(50))
      of 50 ng of the vaccine. In similar experiments, the LH(N)/A vaccine was shown to
      protect mice against challenge with BoNT/A subtypes A(1), A(2), and A(3), which
      is the first demonstration of single-dose protection by a vaccine against the
      principal toxin subtypes of BoNT/A. The LH(N)/B vaccine was also highly
      efficacious, giving an ED(50) of approximately 140 ng to a challenge of 10(3)
      LD(50) of BoNT/B(1). In addition, LH(N)/B provided single-dose protection in mice
      against BoNT/B(4) (nonproteolytic toxin subtype).

PMID- 19398545
TI  - Nonhematopoietic cells control the outcome of infection with Listeria
      monocytogenes in a nucleotide oligomerization domain 1-dependent manner.
AB  - We analyzed the defensive role of the cytosolic innate recognition receptor
      nucleotide oligomerization domain 1 (NOD1) during infection with Listeria
      monocytogenes. Mice lacking NOD1 showed increased susceptibility to systemic
      intraperitoneal and intravenous infection with high or low doses of L.
      monocytogenes, as measured by the bacterial load and survival. NOD1 also
      controlled dissemination of L. monocytogenes into the brain. The increased
      susceptibility to reinfection of NOD1(-/-) mice was not associated with impaired
      triggering of listeria-specific T cells, and similar levels of costimulatory
      molecules or activation of dendritic cells was observed. Higher numbers of
      F480(+) Gr1(+) inflammatory monocytes and lower numbers of F480(-) Gr1(+)
      neutrophils were recruited into the peritoneum of infected WT mice than into the
      peritoneum of infected NOD1(-/-) mice. We determined that nonhematopoietic cells
      accounted for NOD1-mediated resistance to L. monocytogenes in bone marrow
      radiation chimeras. The levels of NOD1 mRNA in fibroblasts and bone marrow
      derived macrophages (BMM) were upregulated after infection with L. monocytogenes
      or stimulation with different Toll-like receptor ligands. NOD1(-/-) BMM,
      astrocytes, and fibroblasts all showed enhanced intracellular growth of L
      monocytogenes compared to WT controls. Gamma interferon-mediated nitric oxide
      production and inhibition of L. monocytogenes growth were hampered in NOD1(-/-)
      BMM. Thus, NOD1 confers nonhematopoietic cell-mediated resistance to infection
      with L. monocytogenes and controls intracellular bacterial growth in different
      cell populations in vitro.

PMID- 19398546
TI  - The metal homeostasis protein, Lsp, of Streptococcus pyogenes is necessary for
      acquisition of zinc and virulence.
AB  - "Cluster 9" family lipoproteins function as ligand-binding subunits of ABC-type
      transporters in maintaining transition metal homeostasis and have been implicated
      in the virulence of several bacteria. While these proteins share high similarity,
      the specific metal that they recognize and whether their role in virulence
      directly involves metal homeostasis cannot be reliably predicted. We examined the
      cluster 9 protein Lsp of Streptococcus pyogenes and found that specific deletion
      of lsp produced mutants highly attenuated in a murine model of soft tissue
      infection. Under standard in vitro conditions, growth of the Lsp(-) mutant was
      indistinguishable from that of the wild type, but growth was defective under zinc
      limited conditions. The growth defect could be complemented by plasmids
      expressing wild-type Lsp but not Lsp engineered to lack its putative lipidation
      residue. Furthermore, Zn(2+) but not Mn(2+) rescued Lsp(-) growth, implicating
      Zn(2+) as the physiological ligand for Lsp. Mutation of residues in the putative
      Zn(2+)-binding pocket generated variants both hypo- and hyper-resistant to zinc
      starvation, and both mutant classes displayed attenuated virulence. Together,
      these data suggest that Lsp is a ligand-binding component of an ABC-type zinc
      permease and that perturbation of zinc homeostasis inhibits the ability of S.
      pyogenes to cause disease in a zinc-limited host milieu.

PMID- 19398547
TI  - Listeria monocytogenes 6-Phosphogluconolactonase mutants induce increased
      activation of a host cytosolic surveillance pathway.
AB  - Infection with wild-type Listeria monocytogenes activates a host cytosolic
      surveillance response characterized by the expression of beta interferon (IFN
      beta). We performed a genetic screen to identify L. monocytogenes transposon
      insertion mutants that induced altered levels of host IFN-beta expression. One
      mutant from this screen induced elevated levels of IFN-beta and harbored a Tn917
      insertion upstream of lmo0558. This study identified lmo0558 as the 6
      phosphogluconolactonase gene (pgl), which encodes the second enzyme in the
      pentose phosphate pathway. pgl mutant L. monocytogenes accumulated and secreted
      large amounts of gluconate, likely derived from labile 6-phosphogluconolactone,
      the substrate of Pgl. The pgl deletion mutant had decreased growth in glucose
      limiting minimal medium but grew normally when excess glucose was added.
      Microarray analysis revealed that the pgl deletion mutant had increased
      expression of several beta-glucosidases, consistent with known inhibition of beta
      glucosidases by 6-phosphogluconolactone. While growth in macrophages was
      indistinguishable from that of wild-type bacteria, pgl mutant L. monocytogenes
      exhibited a 15- to 30-fold defect in growth in vivo. In addition, L.
      monocytogenes harboring an in-frame deletion of pgl was more sensitive to
      oxidative stress. This study identified L. monocytogenes pgl and provided the
      first link between the bacterial pentose phosphate pathway and activation of host
      IFN-beta expression.

PMID- 19398548
TI  - Subcellular localization of the Staphylococcus aureus heme iron transport
      components IsdA and IsdB.
AB  - Staphylococcus aureus is a human pathogen that represents a tremendous threat to
      global public health. An important aspect of S. aureus pathogenicity is the
      ability to acquire iron from its host during infection. In vertebrates, iron is
      sequestered predominantly within heme, the majority of which is bound by
      hemoglobin. To acquire iron, S. aureus binds hemoglobin, removes heme, and
      transports it into the cytoplasm, where heme is degraded. This process is carried
      out by the iron-regulated surface determinant system (Isd); however, the
      mechanism by which hemoglobin recognition occurs is not completely understood.
      Here we report that the surface receptor components of the Isd system, IsdA and
      IsdB, physically interact with each other and are anchored to a discrete location
      within the cell wall. This organized localization pattern is dependent upon the
      iron status of the bacterium. Furthermore, we have found that hemoglobin
      colocalizes with IsdB at discrete sites within the cell wall. Virulence studies
      revealed that IsdB is required for the efficient colonization of the heart and
      that IsdB is differentially expressed within infected organs, suggesting that S.
      aureus experiences various degrees of iron starvation depending on the site of
      infection. These findings significantly expand our understanding of hemoglobin
      iron acquisition and demonstrate an orchestrated pattern of regulation and
      localization for the S. aureus heme iron acquisition system.

PMID- 19398549
TI  - Purification of Legiobactin and importance of this siderophore in lung infection
      by Legionella pneumophila.
AB  - When cultured in a low-iron medium, Legionella pneumophila secretes a siderophore
      (legiobactin) that is both reactive in the chrome azurol S (CAS) assay and
      capable of stimulating the growth of iron-starved legionellae. Using anion
      exchange high-pressure liquid chromatography (HPLC), we purified legiobactin from
      culture supernatants of a virulent strain of L. pneumophila. In the process, we
      detected the ferrated form of legiobactin as well as other CAS-reactive
      substances. Purified legiobactin had a yellow-gold color and absorbed primarily
      from 220 nm and below. In accordance, nuclear magnetic resonance spectroscopy
      revealed that legiobactin lacks aromatic carbons, and among the 13 aliphatics
      present, there were 3 carbonyls. When examined by HPLC, supernatants from L.
      pneumophila mutants inactivated for lbtA and lbtB completely lacked legiobactin,
      indicating that the LbtA and LbtB proteins are absolutely required for
      siderophore activity. Independently derived lbtA mutants, but not a complemented
      derivative, displayed a reduced ability to infect the lungs of A/J mice after
      intratracheal inoculation, indicating that legiobactin is required for optimal
      intrapulmonary survival by L. pneumophila. This defect, however, was not evident
      when the lbtA mutant and its parental strain were coinoculated into the lung,
      indicating that legiobactin secreted by the wild type can promote growth of the
      mutant in trans. Legiobactin mutants grew normally in murine lung macrophages and
      alveolar epithelial cells, suggesting that legiobactin promotes something other
      than intracellular infection of resident lung cells. Overall, these data
      represent the first documentation of a role for siderophore expression in the
      virulence of L. pneumophila.

PMID- 19398550
TI  - Boosting antimicrobial peptides by hydrophobic oligopeptide end tags.
AB  - A novel approach for boosting antimicrobial peptides through end tagging with
      hydrophobic oligopeptide stretches is demonstrated. Focusing on two peptides
      derived from kininogen, GKHKNKGKKNGKHNGWK (GKH17) and HKHGHGHGKHKNKGKKN (HKH17),
      tagging resulted in enhanced killing of Gram-positive Staphylococcus aureus, Gram
      negative Escherichia coli, and fungal Candida albicans. Microbicidal potency
      increased with tag length, also in plasma, and was larger for Trp and Phe
      stretches than for aliphatic ones. The enhanced microbicidal effects correlated
      to a higher degree of bacterial wall rupture. Analogously, tagging promoted
      peptide binding to model phospholipid membranes and liposome rupture,
      particularly for anionic and cholesterol-void membranes. Tagged peptides
      displayed low toxicity, particularly in the presence of serum, and resisted
      degradation by human leukocyte elastase and by staphylococcal aureolysin and V8
      proteinase. The biological relevance of these findings was demonstrated ex vivo
      and in vivo in porcine S. aureus skin infection models. The generality of end
      tagging for facile boosting of antimicrobial peptides without the need for post
      synthesis modification was also demonstrated.

PMID- 19398551
TI  - Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1
      antitrypsin deficiency.
AB  - Z alpha(1)-antitrypsin (ZAAT) deficiency is a disease associated with
      emphysematous lung disease and also with liver disease. The liver disease of AAT
      deficiency is associated with endoplasmic reticulum (ER) stress. SEPS1 is a
      selenoprotein that, through a chaperone activity, decreases ER stress. To
      determine the effect of SEPS1 on ER stress in ZAAT deficiency, we measured
      activity of the grp78 promoter and levels of active ATF6 as markers of the
      unfolded protein response in HepG2 cells transfected with the mutant form of AAT,
      a ZAAT transgene. We evaluated levels of NFkappaB activity as a marker of the ER
      overload response. To determine the effect of selenium supplementation on the
      function of SEPS1, we investigated glutathione peroxidase activity, grp78
      promoter activity, and NFkappaB activity in the presence or absence of selenium.
      SEPS1 reduced levels of active ATF6. Overexpression of SEPS1 also inhibited grp78
      promoter and NFkappaB activity, and this effect was enhanced in the presence of
      selenium supplementation. This finding demonstrates a role for SEPS1 in ZAAT
      deficiency and suggests a possible therapeutic potential for selenium
      supplementation.

PMID- 19398552
TI  - Autoprocessing of the Escherichia coli AIDA-I autotransporter: a new mechanism
      involving acidic residues in the junction region.
AB  - The cleavage of the autotransporter adhesin involved in diffuse adherence (AIDA
      I) of Escherichia coli yields a membrane-embedded fragment, AIDAc, and an
      extracellular fragment, the mature AIDA-I adhesin. The latter remains
      noncovalently associated with AIDAc but can be released by heat treatment. In
      this study we determined the mechanism of AIDA-I cleavage. We showed that AIDA-I
      processing is an autocatalytic event by monitoring the in vitro cleavage of an
      uncleaved mutant protein isolated from inclusion bodies. Furthermore, by
      following changes in circular dichroism spectra and protease resistance of the
      renaturated protein, we showed that the cleavage of the protein is correlated
      with folding. With site-directed deletions, we showed that the catalytic activity
      of the protein lies in a region encompassing amino acids between Ala-667 and Thr
      953, which includes the conserved junction domain of some autotransporters. With
      site-directed point mutations, we also found that Asp-878 and Glu-897 are
      involved in the processing of AIDA-I and that a mutation preserving the acidic
      side chain of Asp-878 was tolerated, giving evidence that this carboxylic acid
      group is directly involved in catalysis. Last, we confirmed that cleavage of AIDA
      I is intramolecular. Our results unveil a new mechanism of auto-processing in the
      autotransporter family.

PMID- 19398553
TI  - ARR19 (androgen receptor corepressor of 19 kDa), an antisteroidogenic factor, is
      regulated by GATA-1 in testicular Leydig cells.
AB  - ARR19 (androgen receptor corepressor of 19 kDa), which encodes for a leucine-rich
      protein, is expressed abundantly in the testis. Further analyses revealed that
      ARR19 was expressed in Leydig cells, and its expression was differentially
      regulated during Leydig cell development. Adenovirus-mediated overexpression of
      ARR19 in Leydig cells inhibited testicular steroidogenesis, down-regulating the
      expression of steroidogenic enzymes, which suggests that ARR19 is an
      antisteroidogenic factor. Interestingly, cAMP/luteinizing hormone attenuated
      ARR19 expression in a fashion similar to that of GATA-1, which was previously
      reported to be down-regulated by cAMP. Sequence analysis of the Arr19 promoter
      revealed the presence of two putative GATA-1 binding motifs. Further analyses
      with 5' deletion and point mutants of putative GATA-1 binding motifs showed that
      these GATA-1 binding sites were critical for high promoter activity. CREB-binding
      protein coactivated GATA-1 and markedly increased the activity of the Arr19
      promoter. Both GATA-1 and CREB-binding proteins occupied the GATA-1 motifs within
      the Arr19 promoter, which was repressed by cAMP treatment. Altogether, these
      findings demonstrate that ARR19 is the target gene of GATA-1 and suggest that
      ARR19 gene expression in testicular Leydig cells is regulated by luteinizing
      hormone/cAMP signaling via the control of GATA-1 expression, resulting in the
      control of testicular steroidogenesis.

PMID- 19398554
TI  - Multimerization and DNA binding properties of INI1/hSNF5 and its functional
      significance.
AB  - INI1/hSNF5/BAF47/SMARCB1 is an HIV-1 integrase (IN)-binding protein that
      modulates viral replication in multiple ways. A minimal IN-binding domain of
      INI1, S6 (amino acids 183-294), transdominantly inhibits late events, and down
      modulation of INI1 stimulates early events of HIV-1 replication. INI1 both
      stimulates and inhibits in vitro integration depending on IN concentration. To
      gain further insight into its role in HIV-1 replication, we purified and
      biochemically characterized INI1. We found that INI1 forms multimeric structures.
      Deletion analysis indicated that the Rpt1 and Rpt2 motifs form the minimal
      multimerization domain. We isolated mutants of INI1 that are defective for
      multimerization using a reverse yeast two-hybrid system. Our results revealed
      that INI1 residues involved in multimerization overlap with IN-binding and
      nuclear export domains and are required for nuclear retention and co-localization
      with IN. Multimerization-defective mutants are also defective for mediating the
      transdominant effect of INI1-S6-(183-294). Furthermore, we found that INI1 is a
      minor groove DNA-binding protein. Although IN binding and multimerization are
      required for INI1-mediated inhibition, the acceptor DNA binding property of INI1
      may be required for stimulation of in vitro strand transfer activities of IN.
      Binding of INI1 to IN results in the formation of presumably inactive high
      molecular weight IN-INI1 complexes, and the multimerization-defective mutant was
      unable to form these complexes. These results indicate that the multimerization
      and IN binding properties of INI1 are necessary for its ability to both inhibit
      integration and influence assembly and particle production, providing insights
      into the mechanism of INI1-mediated effects in HIV-1 replication.

PMID- 19398555
TI  - The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of cystic
      fibrosis transmembrane conductance regulator in airway epithelial cells.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR), a member of the
      ABC transporter superfamily, is a cyclic AMP-regulated chloride channel and a
      regulator of other ion channels and transporters. In epithelial cells CFTR is
      rapidly endocytosed from the apical plasma membrane and efficiently recycles back
      to the plasma membrane. Because ubiquitination targets endocytosed CFTR for
      degradation in the lysosome, deubiquitinating enzymes (DUBs) are likely to
      facilitate CFTR recycling. Accordingly, the aim of this study was to identify
      DUBs that regulate the post-endocytic sorting of CFTR. Using an activity-based
      chemical screen to identify active DUBs in human airway epithelial cells, we
      demonstrated that Ubiquitin Specific Protease-10 (USP10) is located in early
      endosomes and regulates the deubiquitination of CFTR and its trafficking in the
      post-endocytic compartment. small interference RNA-mediated knockdown of USP10
      increased the amount of ubiquitinated CFTR and its degradation in lysosomes, and
      reduced both apical membrane CFTR and CFTR-mediated chloride secretion. Moreover,
      a dominant negative USP10 (USP10-C424A) increased the amount of ubiquitinated
      CFTR and its degradation, whereas overexpression of wt-USP10 decreased the amount
      of ubiquitinated CFTR and increased the abundance of CFTR. These studies
      demonstrate a novel function for USP10 in facilitating the deubiquitination of
      CFTR in early endosomes and thereby enhancing the endocytic recycling of CFTR.

PMID- 19398556
TI  - Distinct biological roles for the notch ligands Jagged-1 and Jagged-2.
AB  - Notch signaling is activated in a subset of non-small cell lung cancer cells
      because of overexpression of Notch3, but the role of Notch ligands has not been
      fully defined. On the basis of gene expression profiling of a panel of non-small
      cell lung cancer cell lines, we found that the predominant Notch ligands were
      JAG1, JAG2, DLL1, and DLL3. Given that Notch ligands reportedly have overlapping
      receptor binding specificities, we postulated that they have redundant biological
      roles. Arguing against this hypothesis, we found that JAG1 and JAG2 were
      differentially regulated; JAG1 expression was dependent upon epidermal growth
      factor receptor (EGFR) activation in HCC827 cells, which require EGFR for
      survival, whereas JAG2 expression was EGFR-independent in these cells.
      Furthermore, HCC827 cells underwent apoptosis following depletion of JAG1 but not
      JAG2, whereas co-culture experiments revealed that depletion of JAG2, but not
      JAG1, enhanced the ability of HCC827 cells to chemoattract THP-1 human monocytes.
      JAG2-depleted HCC827 cells expressed high levels of inflammation-related genes,
      including interleukin 1 (IL1) and a broad range of IL1-regulated cytokines, which
      was attenuated by inhibition of IL1 receptor (IL1R). Our findings suggest that
      JAG1 and JAG2 have distinct biological roles including a previously undiscovered
      role for JAG2 in regulating the expression of cytokines that can promote
      antitumor immunity.

PMID- 19398557
TI  - Protein association and dissociation regulated by ferric ion: a novel pathway for
      oxidative deposition of iron in pea seed ferritin.
AB  - Iron stored in phytoferritin plays an important role in the germination and early
      growth of seedlings. The protein is located in the amyloplast where it stores
      large amounts of iron as a hydrated ferric oxide mineral core within its shell
      like structure. The present work was undertaken to study alternate mechanisms of
      core formation in pea seed ferritin (PSF). The data reveal a new mechanism for
      mineral core formation in PSF involving the binding and oxidation of iron at the
      extension peptide (EP) located on the outer surface of the protein shell. This
      binding induces aggregation of the protein into large assemblies of approximately
      400 monomers. The bound iron is gradually translocated to the mineral core during
      which time the protein dissociates back into its monomeric state. Either the
      oxidative addition of Fe(2+) to the apoprotein to form Fe(3+) or the direct
      addition of Fe(3+) to apoPSF causes protein aggregation once the binding capacity
      of the 24 ferroxidase centers (48 Fe(3+)/shell) is exceeded. When the EP is
      enzymatically deleted from PSF, aggregation is not observed, and the rate of iron
      oxidation is significantly reduced, demonstrating that the EP is a critical
      structural component for iron binding, oxidation, and protein aggregation. These
      data point to a functional role for the extension peptide as an iron binding and
      ferroxidase center that contributes to mineralization of the iron core. As the
      iron core grows larger, the new pathway becomes less important, and Fe(2+)
      oxidation and deposition occurs directly on the surface of the iron core.

PMID- 19398558
TI  - Sgt1 dimerization is negatively regulated by protein kinase CK2-mediated
      phosphorylation at Ser361.
AB  - The kinetochore, which consists of centromere DNA and structural proteins, is
      essential for proper chromosome segregation in eukaryotes. In budding yeast, Sgt1
      and Hsp90 are required for the binding of Skp1 to Ctf13 (a component of the core
      kinetochore complex CBF3) and therefore for the assembly of CBF3. We have
      previously shown that Sgt1 dimerization is important for this kinetochore
      assembly mechanism. In this study, we report that protein kinase CK2
      phosphorylates Ser(361) on Sgt1, and this phosphorylation inhibits Sgt1
      dimerization.

PMID- 19398559
TI  - Contribution of flavin covalent linkage with histidine 99 to the reaction
      catalyzed by choline oxidase.
AB  - The FAD-dependent choline oxidase has a flavin cofactor covalently attached to
      the protein via histidine 99 through an 8alpha-N(3)-histidyl linkage. The enzyme
      catalyzes the four-electron oxidation of choline to glycine betaine, forming
      betaine aldehyde as an enzyme-bound intermediate. The variant form of choline
      oxidase in which the histidine residue has been replaced with asparagine was used
      to investigate the contribution of the 8alpha-N(3)-histidyl linkage of FAD to the
      protein toward the reaction catalyzed by the enzyme. Decreases of 10-fold and 30
      fold in the k(cat)/K(m) and k(cat) values were observed as compared with wild
      type choline oxidase at pH 10 and 25 degrees C, with no significant effect on
      k(cat)/K(O) using choline as substrate. Both the k(cat)/K(m) and k(cat) values
      increased with increasing pH to limiting values at high pH consistent with the
      participation of an unprotonated group in the reductive half-reaction and the
      overall turnover of the enzyme. The pH independence of both (D)(k(cat)/K(m)) and
      (D)k(cat), with average values of 9.2 +/- 3.3 and 7.4 +/- 0.5, respectively, is
      consistent with absence of external forward and reverse commitments to catalysis,
      and the chemical step of CH bond cleavage being rate-limiting for both the
      reductive half-reaction and the overall enzyme turnover. The temperature
      dependence of the (D)k(red) values suggests disruption of the preorganization in
      the asparagine variant enzyme. Altogether, the data presented in this study are
      consistent with the FAD-histidyl covalent linkage being important for the optimal
      positioning of the hydride ion donor and acceptor in the tunneling reaction
      catalyzed by choline oxidase.

PMID- 19398560
TI  - The action and mode of binding of thiazolidinedione ligands at free fatty acid
      receptor 1.
AB  - The endogenous ligands for free fatty acid receptor 1 (FFA1) are medium and
      longer chain free fatty acids. However, a range of selective, small molecule
      ligands have recently been developed as tool compounds to explore the therapeutic
      potential of this receptor, whereas clinically employed thiazolidinedione
      "glitazone" drugs are also agonists at FFA1. Each of these classes of agonist was
      able to promote phosphorylation of the ERK1/2 mitogen-activated protein (MAP)
      kinases in cells able to express human FFA1 on demand. However, although both
      lauric acid and the synthetic agonist GW9508X produced rapid and transient ERK1/2
      MAP kinase phosphorylation, the thiazolidinedione rosiglitazone produced
      responses that were sustained for a substantially longer period. Despite this
      difference, the effects of each ligand required FFA1 and were transduced in each
      case predominantly via G proteins of the Galphaq/Galpha11 family. Different
      glitazone drugs also displayed markedly different efficacy and kinetics of
      sustainability of ERK1/2 MAP kinase phosphorylation. A number of orthosteric
      binding site mutants of FFA1 were generated, and despite variations in the
      changes of potency and efficacy of the three ligand classes in different
      functional end point assays, these were consistent with rosiglitazone also
      binding at the orthosteric site. Four distinct polymorphic variants of human FFA1
      have been described. Despite previous indications that these display differences
      in function and pharmacology, they all responded in entirely equivalent ways to
      lauric acid, rosiglitazone, and GW9508X in measures of ERK1/2 MAP kinase
      phosphorylation, enhancement of binding of [35S]GTPgammaS (guanosine 5'-O-(3
      [35S]thio)triphosphate) to Galphaq, and elevation of intracellular [Ca2+],
      suggesting that individuals expressing each variant are likely to respond
      equivalently to orthosteric agonists of FFA1.

PMID- 19398561
TI  - A professional and personal odyssey.

PMID- 19398563
TI  - The Amiens Strategy: small phase III trials for clinically relevant progress in
      the war against cancer.

PMID- 19398565
TI  - Development and application of a real-time on-line blinded independent central
      review of interim PET scans to determine treatment allocation in lymphoma trials.

PMID- 19398567
TI  - Immediate or delayed docetaxel: does progression-free survival really reflect two
      strategies?

PMID- 19398568
TI  - Androgen deprivation therapy for node-positive prostate cancer: adjuvant does not
      mean salvage.

PMID- 19398570
TI  - Chemotherapy and radiation resistance: version 2.0.

PMID- 19398571
TI  - Symptomatic neurocutaneous melanosis and Dandy-Walker malformation in an adult.

PMID- 19398572
TI  - Margin clearance and outcome in resected pancreatic cancer.
AB  - PURPOSE: Current adjuvant therapies for pancreatic cancer (PC) are inconsistently
      used and only modestly effective. Because a high proportion of patients who
      undergo resection for PC likely harbor occult metastatic disease, any adjuvant
      trials assessing therapies such as radiotherapy directed at locoregional disease
      are significantly underpowered. Stratification based on the probability (and
      volume) of residual locoregional disease could play an important role in the
      design of future clinical trials assessing adjuvant radiotherapy. PATIENTS AND
      METHODS: We assessed the relationships between margin involvement, the proximity
      to operative resection margins and outcome in a cohort of 365 patients who
      underwent operative resection for PC. RESULTS: Microscopic involvement of a
      resection margin by tumor was associated with a poor prognosis. Stratifying the
      minimum clearance of resection margins by 0.5-mm increments demonstrated that
      although median survival was no different to clear margins based on these
      definitions, it was not until the resection margin was clear by more than 1.5 mm
      that optimal long-term survival was achieved. CONCLUSION: These data demonstrate
      that a margin clearance of more than 1.5 mm is important for long-term survival
      in a subgroup of patients. More aggressive therapeutic approaches that target
      locoregional disease such as radiotherapy may be beneficial in patients with
      close surgical margins. Stratification of patients for entry onto future clinical
      trials based on this criterion may identify those patients who benefit from
      adjuvant radiotherapy.

PMID- 19398573
TI  - PTEN expression and KRAS mutations on primary tumors and metastases in the
      prediction of benefit from cetuximab plus irinotecan for patients with metastatic
      colorectal cancer.
AB  - PURPOSE: PTEN, AKT, and KRAS are epidermal growth factor receptor (EGFR)
      downstream regulators. KRAS mutations confer resistance to cetuximab. This
      retrospective study investigated the role of PTEN loss, AKT phosphorylation, and
      KRAS mutations on the activity of cetuximab plus irinotecan in patients with
      metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: A cohort of patients
      with irinotecan-refractory mCRC who were treated with cetuximab plus irinotecan
      was tested for PTEN immunoreactivity (ie, immunohistochemistry; IHC), pAKT IHC,
      and KRAS mutations. Analyses were performed both on primary tumors and on related
      metastases, and the association among IHC, mutational results, and treatment
      outcomes was investigated. RESULTS: One-hundred two patients were eligible.
      Ninety-six primary tumors, 59 metastases, and 53 paired samples were available.
      Forty-nine primary tumors (58% of assessable samples) had a preserved PTEN
      expression (PTEN-positive), whereas 35 (40% of assessable samples) were pAKT
      positive. Levels of concordance between primary tumors and metastases were 60%,
      68%, and 95% for PTEN, pAKT, and KRAS, respectively. PTEN status on primary
      tumors and pAKT status both on primary tumors and on metastases did not predict
      response or progression-free survival (PFS). On metastases, 12 (36%) of 33
      patients with PTEN-positive tumors were responders compared with one (5%) of 22
      who had PTEN-negative tumors (P = .007). The median PFS of patients with PTEN
      positive metastases was 4.7 months compared with 3.3 months for those with PTEN
      negative metastases (hazard ratio [HR], 0.49; P = .005). Patients with PTEN
      positive metastases and KRAS wild type had longer PFS compared with other
      patients (5.5 months v 3.8 months; HR, 0.42; P = .001). CONCLUSION: PTEN loss in
      metastases may be predictive of resistance to cetuximab plus irinotecan. The
      combination of PTEN IHC and KRAS mutational analyses could help to identify a
      subgroup of patients with mCRC who have higher chances of benefiting from EGFR
      inhibition.

PMID- 19398574
TI  - Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology
      and end results program, 1973 to 2005: an analysis of 2,600 patients.
AB  - PURPOSE: To compare clinical features and outcomes of adults and children
      reported to have rhabdomyosarcoma. PATIENTS AND METHODS: We analyzed data from
      1,071 adults (age > 19 years) and 1,529 children (age < or = 19 years) reported
      in the public-access Surveillance, Epidemiology and End Results database as
      having rhabdomyosarcoma, diagnosed from 1973 to 2005. Survival estimates were
      determined using survival time with the end point being death from any cause.
      RESULTS: Adults with rhabdomyosarcoma had significantly worse outcome than
      children (5-year overall survival rates, 27% +/- 1.4% and 61% +/- 1.4%,
      respectively; P < .0001). Tumors in adults were more likely to be at an
      unfavorable site (65% v 55%; P < .0001) and to have histologies that are unusual
      during childhood, particularly the pleomorphic subtype (19%) and not otherwise
      specified (43%). Regional and distant spread was not more frequent in adults.
      Adults had significantly worse outcome than children with similar tumors. The
      most significant difference was in localized disease; 5-year survival estimates
      were 82% +/- 2.0% for children and 47% +/- 2.9% for adults (P < .0001).
      Multivariate analysis showed that age, histologic subtype, primary site location,
      stage, and local control with surgery and/or radiation were significant
      predictors of survival. However, alveolar subtype and unfavorable primary site
      lost significance when analysis was restricted to adults. CONCLUSION: Adults
      reported to have rhabdomyosarcoma had worse survival than children with similar
      tumors. Predictors of poor outcome in children were valid in adults except for
      alveolar histology and unfavorable tumor site.

PMID- 19398575
TI  - Thromboembolism in patients with advanced gastroesophageal cancer treated with
      anthracycline, platinum, and fluoropyrimidine combination chemotherapy: a report
      from the UK National Cancer Research Institute Upper Gastrointestinal Clinical
      Studies Group.
AB  - PURPOSE: Data concerning the prevalence of and outcomes related to thromboembolic
      events (TEs) in patients with advanced gastroesophageal cancer who are undergoing
      chemotherapy are limited. PATIENTS AND METHODS: This was a prospective,
      exploratory analysis of TEs in a randomized, controlled trial of 964 patients
      recruited between 2000 and 2005 and treated with
      epirubicin/platinum/fluoropyrimidine combination chemotherapy for
      advanced/locally advanced gastroesophageal cancer. Regimens were epirubicin (E),
      cisplatin (C), fluorouracil (F; ECF); E, C, capecitabine (X; ECX); E, F,
      oxaliplatin (O; EOF); and EOX. Continuously infused F was administered via a
      central venous access device (CVAD) with 1 mg of warfarin for thromboprophylaxis.
      The principal outcome was the incidence of TEs (venous and arterial) in the whole
      treated patient cohort, according to chemotherapy, associated with CVADs and TE
      related prognoses. RESULTS: The incidences of any, of venous, and of arterial TEs
      among 964 treated patients were 12.1% (95% CI, 10.7 to 14.3), 10.1% (95% CI, 8.3
      to 12.3), and 2.2% (95% CI, 1.4 to 3.4) respectively. There were fewer TEs in the
      O compared with the cisplatin groups (EOF/EOX v ECF/ECX: 7.6% v 15.1%; P =
      .0003). C was identified as a risk factor for TE in multivariate analysis (hazard
      ratio [HR], 0.51; 95% CI, 0.34 to 0.76; P = .001). There was no difference in the
      incidence of TEs for the F group compared with the capecitabine groups. The
      incidence of CVAD-related thrombosis was 7.0% (ECF/EOF arms). Overall survival
      was worse for patients who experienced TEs versus no TEs (median survival, 7.4 v
      10.5 months; HR, 0.8; 95% CI, 0.64 to 0.99; P = .043). CONCLUSION: This analysis
      has prospectively quantified the incidence/pattern of TEs among patients with
      advanced gastroesophageal cancer who were treated with four triplet regimens, has
      demonstrated a differential thrombogenic effect according to platinum use, and
      has noted a poorer outcome associated with TE during treatment. Chemotherapy
      related TE should contribute to the risk/benefit assessment of treatment.

PMID- 19398576
TI  - Knockdown of human N alpha-terminal acetyltransferase complex C leads to p53
      dependent apoptosis and aberrant human Arl8b localization.
AB  - Protein N(alpha)-terminal acetylation is one of the most common protein
      modifications in eukaryotic cells. In yeast, three major complexes, NatA, NatB,
      and NatC, catalyze nearly all N-terminal acetylation, acetylating specific
      subsets of protein N termini. In human cells, only the NatA and NatB complexes
      have been described. We here identify and characterize the human NatC (hNatC)
      complex, containing the catalytic subunit hMak3 and the auxiliary subunits hMak10
      and hMak31. This complex associates with ribosomes, and hMak3 acetylates Met-Leu
      protein N termini in vitro, suggesting a model in which the human NatC complex
      functions in cotranslational N-terminal acetylation. Small interfering RNA
      mediated knockdown of NatC subunits results in p53-dependent cell death and
      reduced growth of human cell lines. As a consequence of hMAK3 knockdown, p53 is
      stabilized and phosphorylated and there is a significant transcriptional
      activation of proapoptotic genes downstream of p53. Knockdown of hMAK3 alters the
      subcellular localization of the Arf-like GTPase hArl8b, supporting that hArl8b is
      a hMak3 substrate in vivo. Taken together, hNatC-mediated N-terminal acetylation
      is important for maintenance of protein function and cell viability in human
      cells.

PMID- 19398577
TI  - Organization of F-actin via concerted regulation of Kette by PTP61F and dAbl.
AB  - We identify Kette, a key regulator of actin polymerization, as a substrate for
      Drosophila protein tyrosine phosphatase PTP61F, as well as for dAbl tyrosine
      kinase. We further show that dAbl is a direct substrate for PTP61F. Therefore,
      Kette phosphotyrosine levels are regulated both directly and indirectly by
      PTP61F. Kette and PTP61F genetically interact in the regulation of F-actin
      organization in pupal eye discs, suggesting that tyrosine phosphorylation is
      essential for the proper regulation of Kette-mediated actin dynamics. This
      hypothesis was confirmed by demonstrating the loss of Kette-mediated F-actin
      organization and lamella formation in S2 cells in a Kette Y482F mutant in which
      the dAbl phosphorylation site was eliminated. Our results establish for the first
      time that PTP61F and dAbl ensure proper actin organization through the
      coordinated and reversible tyrosine phosphorylation of Kette.

PMID- 19398578
TI  - The NF90-NF45 complex functions as a negative regulator in the microRNA
      processing pathway.
AB  - The positive regulatory machinery in the microRNA (miRNA) processing pathway is
      relatively well characterized, but negative regulation of the pathway is largely
      unknown. Here we show that a complex of nuclear factor 90 (NF90) and NF45
      proteins functions as a negative regulator in miRNA biogenesis. Primary miRNA
      (pri-miRNA) processing into precursor miRNA (pre-miRNA) was inhibited by
      overexpression of the NF90 and NF45 proteins, and considerable amounts of pri
      miRNAs accumulated in cells coexpressing NF90 and NF45. Treatment of cells
      overexpressing NF90 and NF45 with an RNA polymerase II inhibitor, alpha-amanitin,
      did not reduce the amounts of pri-miRNAs, suggesting that the accumulation of pri
      miRNAs is not due to transcriptional activation. In addition, the NF90 and NF45
      complex was not found to interact with the Microprocessor complex, which is a
      processing factor of pri-miRNAs, but was found to bind endogenous pri-miRNAs.
      NF90-NF45 exhibited higher binding activity for pri-let-7a than pri-miR-21. Of
      note, depletion of NF90 caused a reduction of pri-let-7a and an increase of
      mature let-7a miRNA, which has a potent antiproliferative activity, and caused
      growth suppression of transformed cells. These findings suggest that the
      association of the NF90-NF45 complex with pri-miRNAs impairs access of the
      Microprocessor complex to the pri-miRNAs, resulting in a reduction of mature
      miRNA production.

PMID- 19398579
TI  - The age-associated decline of glycogen synthase kinase 3beta plays a critical
      role in the inhibition of liver regeneration.
AB  - Aging reduces the regenerative capacities of many tissues. In this paper, we show
      a critical role of the glycogen synthase kinase 3beta (GSK3beta)-cyclin D3
      pathway in the loss of the regenerative capacity of the liver. In young animals,
      high levels of growth hormone (GH) increase expression of GSK3beta, which
      associates with cyclin D3 and triggers degradation of cyclin D3. In livers of old
      mice, the GSK3beta promoter is repressed by C/EBPbeta-histone deacetylase 1
      (HDAC1) complexes, leading to the reduction of GSK3beta. The treatment of old
      mice with GH increases expression of GSK3beta via removal of the C/EBPbeta-HDAC1
      complexes from the GSK3beta promoter. We found that the GSK3beta-cyclin D3
      pathway is also altered in young GH-deficient Little mice and that treatment of
      Little mice with GH corrects the GSK3beta-cyclin D3 pathway. We present evidence
      that GSK3beta regulates liver proliferation by controlling growth-inhibitory
      activity of C/EBPalpha. The downregulation of GSK3beta in young mice inhibits
      liver proliferation after partial hepatectomy via the cyclin D3-C/EBPalpha
      pathway, while the elevation of GSK3beta in old mice accelerates liver
      proliferation. Thus, this paper shows that GSK3beta is a critical regulator of
      liver proliferation and that the reduction of GSK3beta with age causes the loss
      of regenerative capacities of the liver.

PMID- 19398580
TI  - ZNF536, a novel zinc finger protein specifically expressed in the brain,
      negatively regulates neuron differentiation by repressing retinoic acid-induced
      gene transcription.
AB  - Neuronal differentiation is tightly regulated by a variety of factors. In a
      search for neuron-specific genes, we identified a highly conserved novel zinc
      finger protein, ZNF536. We observed that ZNF536 is most abundant in the brain
      and, in particular, is expressed in the developing central nervous system and
      dorsal root ganglia and localized in the cerebral cortex, hippocampus, and
      hypothalamic area. During neuronal differentiation of P19 cells induced by
      retinoic acid (RA), ZNF536 expression is increased at an early stage, and it is
      maintained at a constant level in later stages. Overexpression of ZNF536 results
      in an inhibition of RA-induced neuronal differentiation, while depletion or
      mutation of the ZNF536 gene results in an enhancement of differentiation. We
      further demonstrated that ZNF536 inhibits expression of neuron-specific marker
      genes, possibly through the inhibition of RA response element-mediated
      transcriptional activity, as overexpression of RA receptor alpha can rescue the
      inhibitory role of ZNF536 in neuronal differentiation and neuron-specific gene
      expression. Our studies have identified a novel zinc finger protein that
      negatively regulates neuron differentiation.

PMID- 19398581
TI  - Fbxo45 forms a novel ubiquitin ligase complex and is required for neuronal
      development.
AB  - Fbxo45 is an F-box protein that is restricted to the nervous system. Unlike other
      F-box proteins, Fbxo45 was found not to form an SCF complex as a result of an
      amino acid substitution in the consensus sequence for Cul1 binding. Proteomics
      analysis revealed that Fbxo45 specifically associates with PAM (protein
      associated with Myc), a RING finger-type ubiquitin ligase. Mice deficient in
      Fbxo45 were generated and found to die soon after birth as a result of
      respiratory distress. Fbxo45(-)(/)(-) embryos show abnormal innervation of the
      diaphragm, impaired synapse formation at neuromuscular junctions, and aberrant
      development of axon fiber tracts in the brain. Similar defects are also observed
      in mice lacking Phr1 (mouse ortholog of PAM), suggesting that Fbxo45 and Phr1
      function in the same pathway. In addition, neuronal migration was impaired in
      Fbxo45(-)(/)(-) mice. These results suggest that Fbxo45 forms a novel Fbxo45-PAM
      ubiquitin ligase complex that plays an important role in neural development.

PMID- 19398583
TI  - The yeast AAA+ chaperone Hsp104 is part of a network that links the actin
      cytoskeleton with the inheritance of damaged proteins.
AB  - The yeast AAA(+) chaperone Hsp104 is essential for the development of
      thermotolerance and for the inheritance of prions. Recently, Hsp104, together
      with the actin cytoskeleton, has been implicated in the asymmetric distribution
      of carbonylated proteins. Here, we investigated the interplay between Hsp104 and
      actin by using a dominant-negative variant of Hsp104 (HAP/ClpP) that degrades
      substrate proteins instead of remodeling them. Coexpression of HAP/ClpP causes
      defects in morphology and the actin cytoskeleton. Taking a candidate approach, we
      identified Spa2, a member of the polarisome complex, as an Hsp104 substrate.
      Furthermore, we provided genetic evidence that links Spa2 and Hsp104 to Hof1, a
      member of the cytokinesis machinery. Spa2 and Hof1 knockout cells are affected in
      the asymmetric distribution of damaged proteins, suggesting that Hsp104, Spa2,
      and Hof1 are members of a network controlling the inheritance of carbonylated
      proteins.

PMID- 19398582
TI  - Adiponectin promotes revascularization of ischemic muscle through a
      cyclooxygenase 2-dependent mechanism.
AB  - Adiponectin is a fat-derived plasma protein that has cardioprotective roles in
      obesity-linked diseases. Because cyclooxygenase 2 (COX-2) is an important
      modulator of endothelial function, we investigated the possible contribution of
      COX-2 to adiponectin-mediated vascular responses in a mouse hind limb model of
      vascular insufficiency. Ischemic insult increased COX-2 expression in endothelial
      cells of wild-type mice, but this induction was attenuated in adiponectin
      knockout mice. Ischemia-induced revascularization was impaired in mice in which
      the Cox-2 gene is deleted in Tie2-Cre-expressing cells. Adenovirus-mediated
      overexpression of adiponectin enhanced COX-2 expression and revascularization of
      ischemic limbs in control mice, but not in targeted Cox-2-deficient mice. In
      cultured endothelial cells, adiponectin protein increased COX-2 expression, and
      ablation of COX-2 abrogated the adiponectin-stimulated increases in endothelial
      cell migration, differentiation, and survival. Ablation of calreticulin (CRT) or
      its adaptor protein CD91 diminished adiponectin-stimulated COX-2 expression and
      endothelial cell responses. These observations provide evidence that adiponectin
      promotes endothelial cell function through CRT/CD91-mediated increases in COX-2
      signaling. Thus, disruption of the adiponectin-COX-2 regulatory axis in
      endothelial cells could participate in the pathogenesis of obesity-related
      vascular diseases.

PMID- 19398584
TI  - DNA damage-induced phosphorylation of TRF2 is required for the fast pathway of
      DNA double-strand break repair.
AB  - Protein kinases of the phosphatidylinositol 3-kinase-like kinase family,
      originally known to act in maintaining genomic integrity via DNA repair pathways,
      have been shown to also function in telomere maintenance. Here we focus on the
      functional role of DNA damage-induced phosphorylation of the essential mammalian
      telomeric DNA binding protein TRF2, which coordinates the assembly of the
      proteinaceous cap to disguise the chromosome end from being recognized as a
      double-stand break (DSB). Previous results suggested a link between the transient
      induction of human TRF2 phosphorylation at threonine 188 (T188) by the ataxia
      telangiectasia mutated protein kinase (ATM) and the DNA damage response. Here, we
      report evidence that X-ray-induced phosphorylation of TRF2 at T188 plays a role
      in the fast pathway of DNA DSB repair. These results connect the highly transient
      induction of human TRF2 phosphorylation to the DNA damage response machinery.
      Thus, we find that a protein known to function in telomere maintenance, TRF2,
      also plays a functional role in DNA DSB repair.

PMID- 19398585
TI  - Regulation of H3K4 trimethylation via Cps40 (Spp1) of COMPASS is
      monoubiquitination independent: implication for a Phe/Tyr switch by the catalytic
      domain of Set1.
AB  - The multiprotein complex Set1/COMPASS is the founding member of the histone H3
      lysine 4 (H3K4) methyltransferases, whose human homologs include the MLL and
      hSet1 complexes. COMPASS can mono-, di-, and trimethylate H3K4, but transitioning
      to di- and trimethylation requires prior H2B monoubiquitination followed by
      recruitment of the Cps35 (Swd2) subunit of COMPASS. Another subunit, Cps40
      (Spp1), interacts directly with Set1 and is only required for transitioning to
      trimethylation. To investigate how the Set1 and COMPASS subunits establish the
      methylation states of H3K4, we generated a homology model of the catalytic domain
      of Saccharomyces cerevisiae yeast Set1 and identified several key residues within
      the Set1 catalytic pocket that are capable of regulating COMPASS's activity. We
      show that Tyr1052, a putative Phe/Tyr switch of Set1, plays an essential role in
      the regulation of H3K4 trimethylation by COMPASS and that the mutation to
      phenylalanine (Y1052F) suppresses the loss of Cps40 in H3K4 trimethylation
      levels, suggesting that Tyr1052 functions together with Cps40. However, the loss
      of H2B monoubiquitination is not suppressed by this mutation, while Cps40 is
      stably assembled in COMPASS on chromatin, demonstrating that Tyr1052- and Cps40
      mediated H3K4 trimethylation takes place following and independently of H2B
      monoubiquitination. Our studies provide a molecular basis for the way in which
      H3K4 trimethylation is regulated by Tyr1052 and the Cps40 subunit of COMPASS.

PMID- 19398587
TI  - Intra- and extra-familial child molestation as pathways building on parental and
      relational deficits and personality disorders.
AB  - This article addresses the intra- and extra-familial pathways of child
      molestation. The data presented show preliminary evidence that the difference
      between the intra- and extra-familial routes can be explained by schizoid and
      avoidant (intra-familial) and antisocial and passive-aggressive (extra-familial)
      personality structures. This study also reveals that the amount of warmth and
      autonomy received during childhood is associated with both intra- and extra
      familial child-molesting behaviour. These findings contribute to a further
      explanation of this deviant sexual conduct and to the development and
      differentiation of the treatment of child molesters.

PMID- 19398588
TI  - Individual and institutional characteristics related to inmate victimization.
AB  - This study examines the effect of inmate and institutional characteristics on
      inmate victimization during incarceration. In addition, it examines whether
      factors related to inmate victimization varies by perpetrator type, specifically
      inmate versus staff victimizer. Self-reported data from 247 male and female
      inmates confined to eight correctional institutions are collected, including
      questions regarding their experiences of staff-on-inmate and inmate-on-inmate
      victimization. Results show that similar institutional-level variables predict
      both types of inmate victimization; however, there are some differences between
      outcomes based on inmate-level characteristics. The authors address possible
      explanations for the results and suggest several policy implications to reduce
      the incidence of prison violence.

PMID- 19398586
TI  - Targeted knock-in mice expressing mutations of CD28 reveal an essential pathway
      for costimulation.
AB  - Despite extensive study, the role of phosphatidylinositol 3-kinase (PI3-kinase)
      activation in CD28 function has been highly contentious. To definitively address
      this question, we generated knock-in mice expressing mutations in two critical
      domains of the cytoplasmic tail of CD28. Mutation of the proximal tyrosine motif
      interrupted PI3-kinase binding and prevented CD28-dependent phosphorylation of
      protein kinase B (PKB)/Akt; however, there was no detectable effect on
      interleukin-2 (IL-2) secretion, expression of Bcl-X(L), or on T-cell function in
      vivo. Furthermore, we demonstrate that signaling initiated by the C-terminal
      proline motif is directly responsible for tyrosine phosphorylation of
      phosphoinosotide-dependent kinase 1, protein kinase C theta, and glycogen
      synthase kinase 3beta, as well as contributing to threonine phosphorylation of
      PKB. T cells mutated in this domain were profoundly impaired in IL-2 secretion,
      and the mice had marked impairment of humoral responses as well as less severe
      disease manifestations in experimental allergic encephalomyelitis. These data
      demonstrate that the distal proline motif initiates a critical nonredundant
      signaling pathway, whereas direct activation of PI3-kinase by the proximal
      tyrosine motif of CD28 is not required for normal T-cell function.

PMID- 19398589
TI  - Persistent dispositionalism in interactionist clothing: fundamental attribution
      error in explaining prison abuse.
AB  - The Stanford Prison Experiment demonstrated some important lessons about the
      power of social situations, settings, and structures to shape and transform
      behavior. At the time the study was done, the authors scrupulously addressed the
      issue of whether and how the dispositions or personality traits of the
      participants might have affected the results. Here the authors renew and reaffirm
      their original interpretation of the results and apply this perspective to some
      recent socially and politically significant events.

PMID- 19398590
TI  - Social class differences in self, attribution, and attention: socially expansive
      individualism of middle-class Americans.
AB  - Although U.S. culture strongly sanctions the ideal of independence, the specific
      ways in which independence is realized may be variable depending, among other
      factors, on social class. Characterized by relative scarcity of social and
      material resources, working-class (WC) Americans were expected to strongly value
      self-reliance. In contrast, with choices among abundant resources, middle-class
      (MC) Americans were expected to value personal control and social expansiveness.
      In support of this analysis, relative to their WC counterparts, MC Americans
      reported more support from friends and greater likelihood of giving and receiving
      advice but less self-reliance (Study 1). Furthermore, we found evidence that this
      social difference has cognitive consequences: College students with MC
      backgrounds were more likely than their WC counterparts were to endorse
      situational attributions for others' behavior (Studies 2a and 2b) as well as to
      show holistic visual attention (Study 3).

PMID- 19398591
TI  - Do the RCPath-published workload guidelines underestimate the work rate
      achievable in subspecialty practice in cellular pathology?

PMID- 19398592
TI  - My approach to interstitial lung disease using clinical, radiological and
      histopathological patterns.
AB  - The complex world of interstitial lung disease presents nearly insurmountable
      challenges to the general surgical pathologist faced with a lung biopsy in this
      setting. The pathology is often inflammatory and always requires clinical and
      radiological context for a relevant and clinically useful histopathological
      diagnosis. A pattern-based histopathological approach to interstitial lung
      disease provides a "map" for the general pathologist to navigate this area
      successfully, especially so when used with aid of the clinical and radiological
      patterns of presentation.

PMID- 19398593
TI  - Laboratory services for thyroglobulin and implications for monitoring of
      differentiated thyroid cancer.
AB  - Serum thyroglobulin is used as a marker for monitoring differentiated thyroid
      cancer. There are a number of analytical challenges: the need for stability of
      the assay over decades, differences in assay bias, and interference in
      immunoassays by endogenous thyroglobulin antibodies. Improved precision at low
      analyte concentrations is desirable. Approaches to identifying assay interference
      are discussed. No single approach is likely to be successful on all occasions.
      Decision limits should be assay-specific, and clinicians should be aware of the
      limitations of current immunoassays.

PMID- 19398594
TI  - MicroRNA involvement in the pathogenesis and management of breast cancer.
AB  - MicroRNAs (miRNAs) are a highly abundant class of endogenous small non-coding
      RNAs (18-25 nucleotides in length) that regulate gene expression by targeting
      protein-coding mRNAs post-transcriptionally. miRNAs have been implicated in
      cancer development and progression. As miRNAs and their regulatory functions are
      further revealed, the more the importance of miRNA-directed gene regulation is
      emphasised. In the human genome, 695 mature miRNAs have been identified, although
      computational calculation predicts that this may increase to >1000. Deregulation
      of miRNA expression profiles is thought to be implicated in the pathogenesis of
      many human cancers including breast tumours. Breast cancer subtypes are observed
      to have deranged miRNA expression signatures, which makes miRNAs important
      targets for developing a novel molecular classification of breast cancer and
      opening avenues for more individualised treatment strategies for patients with
      breast cancer.

PMID- 19398595
TI  - Limited value of testing for intrinsic factor antibodies with negative gastric
      parietal cell antibodies in pernicious anaemia.
AB  - BACKGROUND: The appropriate testing strategy for diagnosing pernicious anaemia
      using gastric parietal cell (GPC) and/or intrinsic factor antibodies (IFA) is
      controversial. Intrinsic factor antibodies are found in only about 70% of cases.
      Indirect immunofluorescence screening for gastric parietal cell antibodies is
      more sensitive, labour intensive, and less specific. METHODS: The frequency of
      antibody positivity (IFA and/or GPC) was retrospectively examined in patients
      tested for both autoantibodies over a three-year period. It was investigated
      whether B12 levels were related to antibody status. These findings were validated
      in a prospective study of IFA in 91 GPC negative patients with low B12 levels.
      RESULTS: Of 847 samples identified in the retrospective study, 4 (0.47%) were
      positive for only intrinsic factor antibodies, 731 (86.3%) positive for GPC
      alone, and 112 (13.2%) for both. Student t test on log-transformed data showed
      B12 levels had no bearing on autoantibody status. 91 consecutive patients with
      low B12 levels were tested for both autoantibodies; all were negative for gastric
      parietal cell antibodies. Only one sample was positive for intrinsic factor
      antibody using the porcine intrinsic factor assay, but was negative by a human
      recombinant intrinsic factor-based ELISA. CONCLUSIONS: This study provides
      evidence that testing for gastric parietal cell antibodies is an appropriate
      screening test for pernicious anaemia, with intrinsic factor antibodies reserved
      for confirmatory testing or in patients with other autoantibodies that mask the
      GPC pattern; B12 levels are not related to autoantibody status.

PMID- 19398596
TI  - Autoimmune pancytopenia following combination chemotherapy for chronic
      lymphocytic leukaemia.
AB  - Autoimmune haemolysis or thrombocytopenia can complicate purine nucleoside
      monotherapy for chronic lymphocytic leukaemia (CLL), but Evans syndrome is rare.
      This is a report of the occurrence of pancytopenia secondary to a unique
      combination of red cell aplasia with autoimmune thrombocytopenia and neutropenia
      in a patient with CLL following treatment with fludarabine and cyclophosphamide.
      This case is unusual for the simultaneous targeting of three haemopoietic
      lineages by immune dysfunction following fludarabine and cyclophosphamide, which
      is a treatment regimen believed to reduce autoimmune haematological toxicity in
      CLL.

PMID- 19398597
TI  - Synchronous lung tumours in a patient with metachronous colorectal carcinoma and
      a germline MSH2 mutation.
AB  - Mutations of DNA mismatch repair genes are characterised by microsatellite
      instability and are implicated in carcinogenesis. This mutation susceptible
      phenotype has been extensively studied in patients with hereditary non-polyposis
      colon carcinoma, but little is known of the contribution of such mutations in
      other tumour types, particularly non-small-cell lung carcinoma. This report
      describes the occurrence of two synchronous lung tumours, one mimicking a
      metastatic colon carcinoma, in a male patient with a history of metachronous
      colonic carcinoma. Immunohistochemistry supported a pulmonary origin for both
      lesions. Mismatch repair protein immunohistochemistry showed loss of MSH2 and
      MSH6 expression in both colonic tumours and in one lung tumour showing enteric
      differentiation. Subsequent mutational analysis demonstrated a deleterious
      germline mutation of the MSH2 mismatch repair gene. The significance of these
      findings and the practical diagnostic difficulties encountered in this case are
      discussed.

PMID- 19398600
TI  - Peritoneal lymphomatosis, a morphological look alike to peritoneal
      carcinomatosis: an autopsy report.

PMID- 19398598
TI  - Vascular endothelial growth factor activity after switching of bisphosphonate
      treatment for metastatic breast cancer.
AB  - BACKGROUND: Recent data have shown a fall in vascular endothelial growth factor
      (VEGF) concentrations after bisphosphonate (BP) treatment in BP-naive patients.
      It has therefore been proposed that BPs may have in vivo anti-VEGF effects. AIMS:
      To explore whether VEGF concentrations change after administration of a more
      potent BP in patients receiving long-term BP treatment. METHODS: 31 patients with
      breast cancer who had progressive metastatic bone disease despite treatment with
      early-generation BPs were switched to zoledronic acid. Serum VEGF concentrations
      were measured at baseline, and weeks 1, 2, 3, 4, 8 and 12. RESULTS: VEGF
      concentration per platelet count did not change significantly at any time during
      the 12 weeks after treatment with zoledronic acid. CONCLUSIONS: Switching to
      zoledronic acid did not suppress circulating serum VEGF concentrations in BP
      pretreated patients. Novel approaches to assess the effect of BPs on the bone
      milieu may provide further insight into the possible antiangiogenic properties of
      BPs.

PMID- 19398601
TI  - Statin effects on LDL and HDL cholesterol in South Asian and white populations.
AB  - Inasmuch as statins appear to exhibit altered efficacy in some Asian populations
      (predominantly East Asian), current lipid guidelines recommend the use of lower
      statin doses in all Asians. Whether this should also apply to South Asians, a
      population at high risk for coronary heart disease, remains unclear. The authors
      evaluated the lipid-modifying effects of statins in South Asian and white
      patients with established coronary heart disease. Atorvastatin (median dose=20
      mg/d in both groups) produced similar decreases in low-density lipoprotein
      cholesterol (LDL-c) in South Asian (43%) and white (41%) patients and raised high
      density lipoprotein cholesterol (HDL-c) by 19% in South Asians and by 12% in
      whites. Simvastatin (median dose=20 mg/d in both groups) reduced LDL-c by 35% in
      South Asians and by 37% in whites while raising HDL-c by 12% in both groups.
      Using a multiple linear regression model (atorvastatin equivalent), the expected
      decrease in LDL-c for 10 mg atorvastatin and 20 mg atorvastatin was similar
      between the groups. Results indicate that atorvastatin and simvastatin, at
      commonly prescribed doses, modulate LDL-c and HDL-c levels to a similar degree in
      both South Asians and whites with documented coronary heart disease. These
      findings suggest that South Asian patients may be treated with atorvastatin and
      simvastatin at doses typically applied to white patients.

PMID- 19398602
TI  - Safety, pharmacokinetics, and pharmacodynamics of single doses of LXR-623, a
      novel liver X-receptor agonist, in healthy participants.
AB  - Liver X-receptor (LXR) agonists have been postulated to enhance reverse
      cholesterol transport (RCT), a process believed to shuttle cholesterol from the
      periphery back to the liver. Enhancing RCT via the upregulation of cholesterol
      transporters such as the adenosine triphosphate-binding cassettes ABCA1 and ABCG1
      could therefore inhibit the progression of atherosclerosis. LXR-623 is a
      synthetic ligand for LXRs alpha and beta that has shown promise in animal models
      of atherosclerosis. The authors present results from a single ascending-dose
      study of the safety, pharmacokinetics, and pharmacodynamics of LXR-623 in healthy
      participants. LXR-623 was absorbed rapidly with peak concentrations (C(max))
      achieved at approximately 2 hours. The C(max) and area under the concentration
      time curve increased in a dose-proportional manner. The mean terminal disposition
      half-life was between 41 and 43 hours independently of dose. LXR activation
      resulted in a dose-dependent increase in ABCA1 and ABCG1 expression. The effect
      of LXR-623 concentration on ABCA1 and ABCG1 expression was further characterized
      via a population pharmacokinetic-pharmacodynamic analysis, yielding EC(50)
      estimates of 526 ng/mL and 729 ng/mL, respectively. Central nervous system
      related adverse events were observed at the 2 top doses tested. The
      pharmacodynamic effects described here are the first demonstration of "target
      engagement" by an LXR agonist in humans.

PMID- 19398603
TI  - Effects of statins on the pharmacokinetics of midazolam in healthy volunteers.
AB  - Lipid-lowering agents, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors
      (statins), are widely used to prevent coronary artery disease and often
      coadministered with other drugs, but there is a possibility that they induce
      pharmacological interactions with concomitant drugs. The authors aimed to
      investigate whether statins have any influence on cytochrome P450 (CYP) 3A4
      enzyme activity. Eleven healthy volunteers were enrolled and evaluated for the
      effects of statins on the pharmacokinetics of midazolam in an open-label,
      randomized, 3-way crossover trial with simvastatin 10 mg, atorvastatin 10 mg, and
      pitavastatin 2 mg. The statins had no effects on the pharmacokinetics of
      midazolam and its metabolite, 1'-hydroxymidazolam. Furthermore, the area under
      the concentration-time curve ratios for 1'-hydroxymidazolam/midazolam from 0 to
      10 hours showed no significant differences among 3 statins (simvastatin: 0.32 +/-
      0.09, atorvastatin: 0.31 +/- 0.09, and pitavastatin: 0.31 +/- 0.12). These data
      suggest that statins, at least at low doses used in the present study, do not
      affect CYP3A4 and can be used safely without influencing CAP3A4 enzyme activity.

PMID- 19398604
TI  - Clopidogrel inhibits CYP2C19-dependent hydroxylation of omeprazole related to
      CYP2C19 genetic polymorphisms.
AB  - This study explores the impact of clopidogrel on the pharmacokinetics of
      omeprazole related to CYP2C19 genetic polymorphisms. Twelve healthy volunteers (6
      CYP2C19*1/*1, 5 CYP2C19*2/*2, and 1 CYP2C19*2/*3) are enrolled in a 2-phase
      randomized crossover trial. In each phase, the volunteers are administered a
      single oral dose of omeprazole 40 mg after pretreatment of either placebo or
      clopidogrel (300 mg on the first day and then 75 mg once daily for 3 consecutive
      days). Plasma concentrations of omeprazole and its metabolites are quantified by
      high-performance liquid chromatography with UV detection. After clopidogrel
      treatment, the AUC(0-infinity) of omeprazole increases by 30.02% +/- 18.03% (P =
      .004) and that of 5-hydroxyomeprazole decreases by 24.30% +/- 11.66% (P = .032)
      in CYP2C19*1/*1. The AUC(0-infinity) ratios of omeprazole to 5-hydroxyomeprazole
      increase by 74.98% +/- 35.48% (P = .001) and those of omeprazole to omeprazole
      sulfone do not change significantly (P = .832) in CYP2C19*1/*1. No significant
      alteration is observed in CYP2C19*2/*2 or *3. Clopidogrel inhibits CYP2C19
      dependent hydroxylation of omeprazole in CYP2C19*1/*1 and has no impact on CYP3A4
      catalyzed sulfoxidation of omeprazole.

PMID- 19398605
TI  - Inflammatory mediators in Chinese patients with congestive heart failure.
AB  - In this study, circulating levels of proinflammatory and anti-inflammatory
      mediators are studied in patients with chronic heart failure (CHF) in China.
      Sixty-five patients with CHF and 32 control subjects are studied. The
      proinflammatory and anti-inflammatory cytokines interleukin (IL)-6, IL-10, tumor
      necrosis factor (TNF)-alpha, atrial natriuretic peptide (ANP), and brain
      natriuretic peptide (BNP) in plasma are determined by immunoradiometric assay
      kits. Catecholamine (CA) in plasma is evaluated by high-performance liquid
      chromatography. Plasma levels of IL-6, IL-10, TNF-alpha, ANP, BNP, and CA in CHF
      patients are significantly higher than those in control subjects. Patients in a
      higher New York Heart Association (NYHA) class show higher concentrations of
      inflammatory mediators than those in a lower NYHA class, although the ratio of
      plasma IL-10 to TNF-alpha in patients with CHF is significantly lower than in the
      control group. It is concluded that proinflammatory and anti-inflammatory
      cytokine levels are increased and IL-10/TNF-alpha is decreased in Chinese
      patients with CHF.

PMID- 19398606
TI  - Effects of prolonged formalin fixation on diagnostic immunohistochemistry in
      domestic animals.
AB  - Immunohistochemistry (IHC) is routinely used in diagnostic pathology to detect
      infectious agents, to immunophenotype neoplastic cells, and to prognosticate
      neoplastic diseases. Formalin fixation is considered a limiting factor for IHC
      because formalin can cross-link antigens and mask epitopes. Prolonged formalin
      fixation is presumed to result in decreased antigen detection; however, this
      effect has only been evaluated with a few antibodies. The goal of this study was
      to evaluate the effect of prolonged formalin fixation on the immunohistochemical
      detection of 61 different antigens. Approximately 5-mm-thick tissue slices were
      fixed in 10% neutral-buffered formalin. Tissue slices were removed from formalin,
      processed, and paraffin-embedded at 1-day, 3-day, and then at approximately 1
      week intervals. IHC was performed on all sections in tandem after all tissues
      were processed. Immunoreactions were evaluated by three pathologists according to
      a four-tier grading system. Immunoreactivity of cytokeratin 7, high-molecular
      weight cytokeratin, and laminin was diminished by prolonged formalin fixation.
      However, immunohistochemical reactivity remained moderate to strong with up to 7
      weeks of fixation for all other antibodies. These results suggest that prolonged
      formalin fixation has minimal effects on antigen detection for most commonly used
      antibodies. These results further validate the use of IHC in diagnostic
      pathology.

PMID- 19398607
TI  - Immunohistochemical analysis of laryngeal muscles in normal horses and horses
      with subclinical recurrent laryngeal neuropathy.
AB  - We used immunohistochemistry to examine myosin heavy-chain (MyHC)-based fiber
      type profiles of the right and left cricoarytenoideus dorsalis (CAD) and
      arytenoideus transversus (TrA) muscles of six horses without laryngoscopic
      evidence of recurrent laryngeal neuropathy (RLN). Results showed that CAD and TrA
      muscles have the same slow, 2a, and 2x fibers as equine limb muscles, but not the
      faster contracting fibers expressing extraocular and 2B MyHCs found in laryngeal
      muscles of small mammals. Muscles from three horses showed fiber-type grouping
      bilaterally in the TrA muscles, but only in the left CAD. Fiber-type grouping
      suggests that denervation and reinnervation of fibers had occurred, and that
      these horses had subclinical RLN. There was a virtual elimination of 2x fibers in
      these muscles, accompanied by a significant increase in the percentage of 2a and
      slow fibers, and hypertrophy of these fiber types. The results suggest that
      multiple pathophysiological mechanisms are at work in early RLN, including
      selective denervation and reinnervation of 2x muscle fibers, corruption of neural
      impulse traffic that regulates 2x and slow muscle fiber types, and compensatory
      hypertrophy of remaining fibers. We conclude that horses afflicted with mild RLN
      are able to remain subclinical by compensatory hypertrophy of surviving muscle
      fibers.

PMID- 19398608
TI  - Epstein-Barr virus-associated gastric carcinoma: a distinct carcinoma of gastric
      phenotype by claudin expression profiling.
AB  - Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) is a distinct subtype
      with characteristic clinicopathological features. To better characterize its
      cellular characteristics, 43 cases of EBV-associated GC, 68 cases of EBV-negative
      GC, and non-neoplastic gastric mucosa in adults and fetuses were examined
      immunohistochemically. We quantified the expression of the major tight-junction
      protein claudin (CLDN) -1, -3, -4, -7, and -18 together with gastric mucins
      (MUC5AC and MUC6), intestinal mucin (MUC2), and CD10. EBV-associated GC showed a
      high frequency of CLDN18 expression (84%) and a low frequency of CLDN3 expression
      (5%). This expression profile corresponded to that of normal gastric epithelium
      in adults and fetuses. Almost half of the EBV-associated GC cases demonstrated
      gastric mucin expression, whereas the other half lacked mucin or CD10 expression.
      In contrast, as demonstrated by the expression profiles of CLDN3 and CLDN18, EBV
      negative GC comprised a heterogeneous group of four different CLDN phenotypes:
      gastric, intestinal, mixed, and an undifferentiated type with variable expression
      patterns of mucins. These results indicate that EBV-associated GC is considerably
      homogenous with regard to cellular differentiation and that it preserves well the
      nature of the cells of origin. EBV-associated GC may undergo distinct
      carcinogenic processes, which differ from those of EBV-negative GC.

PMID- 19398609
TI  - Mechanical strain induces expression of C-reactive protein in human blood
      vessels.
AB  - C-reactive protein (CRP) is a powerful independent risk factor for cardiovascular
      diseases. Elevated mechanical strain on vessels induces the local expression of
      proinflammatory cytokines. We hypothesized that mechanical strain on vessels may
      induce local CRP expression. Human saphenous vein and internal mammary artery
      (IMA) rings were stretched in vitro with a mechanical strength of 1, 3, or 5 g.
      Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent
      assay results showed that mechanical stretching significantly induced CRP mRNA
      and protein expression in the saphenous vein and IMA rings in a strength
      dependent manner reaching a maximum at a mechanical strength of 3 g, but CRP
      expression returned at strengths of >5 g. In vessels, mechanical strain-induced
      CRP expression was blocked by two stretch-activated ion channel (SAC) blockers:
      GdCl(3) and streptomycin. Mechanical strain also increased activation of nuclear
      factor kappaB (NF-kappaB), which was detected with a nonradioactive NF-kappaB
      p50/p65 EZ-TFA transcription factor assay. Mechanical strain-induced NF-kappaB
      activation was blocked by SAC blockers and the NF-kappaB inhibitor (SN50, H-Ala
      Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Val-Gln-Arg-Lys-Arg
      Gln-Lys-Leu-Met-Pro-OH). SN50 also blocked mechanical strain-induced CRP
      expression in vessels. In conclusion, mechanical strain induces CRP expression in
      IMAs and saphenous veins by activating the SAC-induced NF-kappaB pathway.

PMID- 19398610
TI  - When family means more (or less) than genetics: the intersection of culture,
      family and genomics.
AB  - There is renewed interest in the use of family history to predict individual
      disease susceptibility, and as a result, standardized online family history tools
      are being developed and marketed as a "new genetic test." It is not known how
      cultural variations in definitions of family influence collection of these data
      or what is the best format to use. This is significant given that the populations
      who carry the greatest burden of the target diseases have not been considered in
      efforts to test these tools. A qualitative study with a convenience sample of 19
      Japanese Americans and Samoan Americans, two groups at high risk for type 2
      diabetes, was conducted to explore the process of collecting family history. A
      particularly strong finding was the high degree of acceptance experienced by the
      participants with the process and their pride in visualizing their family
      graphically displayed in pedigrees. It was also found that Samoans included those
      linked by nonbiological ties in their families, which reflects their cultural
      practices. Further research is needed to assess the most effective and efficient
      way to gather family history given the complexities surrounding the deceptively
      simple concept of family.

PMID- 19398611
TI  - Clinical Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and
      Pediatric Patients, 2009.

PMID- 19398612
TI  - A.S.P.E.N. Clinical Guidelines: nutrition support of the critically ill child.

PMID- 19398614
TI  - Emergent literacy intervention for prekindergarteners at risk for reading
      failure.
AB  - This study examined the effectiveness of an assessment and intervention study
      targeting prekindergarten children at risk for reading failure. Across 38 child
      care sites, 220 children were identified as "at risk" for reading failure due to
      their performance on a screening measure of early literacy skills and randomly
      assigned to receive immediate or delayed intervention. The intervention consisted
      of eighteen 30-minute lessons delivered twice weekly for 9 weeks and focused on
      teaching critical emergent literacy skills within small groups. Hierarchical
      linear models were used to nest children within center and measure treatment and
      dosage effects for students' residualized gains in rhyming, alliteration, picture
      naming, and print and letter knowledge skills. Results indicated significant
      treatment effects on two of four outcome variables (rhyming and alliteration) and
      significant dosage effects on all four variables. The study demonstrated a
      significant positive impact of this intervention for prekindergartners at risk
      for reading failure.

PMID- 19398613
TI  - Guidelines for the Provision and Assessment of Nutrition Support Therapy in the
      Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and
      American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).

PMID- 19398615
TI  - Leadership in academic psychiatry: the vision, the "givens," and the nature of
      leaders.

PMID- 19398616
TI  - Promoting the teaching of psychiatric ethics.

PMID- 19398617
TI  - Memoirs of a triple board pioneer.

PMID- 19398619
TI  - A personal perspective on triple board certification.

PMID- 19398620
TI  - Innovative training in pediatrics, general psychiatry, and child psychiatry:
      background, outcomes, and experiences.
AB  - OBJECTIVES: The authors describe the history, rationale, and outcomes of combined
      training programs in pediatrics, psychiatry, and child psychiatry ("triple
      board"), including narrative feedback from graduates and reflections upon the
      important components of the program. METHODS: This article reviews the background
      and experiences of triple board graduates and programs using published data
      regarding triple board history and outcomes, reflections and follow-up
      information collected from triple board graduates as part of a national triple
      board network development, and direct experiences with triple board training
      programs. RESULTS: The triple board training program provides a unique training
      background for physicians who serve children and their families. The programs
      train physicians who seek out additional training opportunities, succeed in
      passing board certification examinations, and earn national recognition.
      Additionally, feedback from graduates reflects satisfaction with training
      experiences. CONCLUSION: The outcomes from this experiment in integrated training
      in child psychiatry support the consideration of expanding triple board training
      programs and introducing new innovations in training.

PMID- 19398622
TI  - The effect of psychiatric third-year rotation setting on academic performance,
      student attitudes, and specialty choice.
AB  - OBJECTIVE: Few studies have directly compared the effects of third-year clerkship
      rotation type on measures of academic performance, student attitudes about
      psychiatry and psychiatric patients, and level of interest in psychiatry as a
      career. The goal of this study was to assess the extent to which rotation type
      influenced these outcome variables among third-year medical students. METHODS:
      The authors conducted a prospective study of 647 third-year medical students
      administratively assigned to one of three clinical settings: an acute inpatient
      ward, a hospital-based consultation-liaison service, and an outpatient mental
      health care clinic. Academic performance was estimated using scores from a
      nationally standardized examination provided by the National Board of Medical
      Examiners (NBME), while responses to an anonymous survey developed by the
      investigators were used as indicators of student attitudes about and interest in
      psychiatry as a potential career field. Administrative residency match data were
      collected on all participants. RESULTS: Rotation type had no effect on NBME exam
      scores after controlling for grade point average, age, gender, rotation order,
      and rotation year. Although individuals who rotated on the inpatient service
      scored an average of 1.8 points higher on the examination relative to individuals
      who rotated on the consultation service, this small difference was not considered
      academically meaningful. Similarly, there were no statistically meaningful
      patterns that emerged between survey responses and rotation type. Approximately
      4% of our sample matched into psychiatric residencies after graduating from
      medical school. Rotation type and survey responses were not statistically
      correlated with specialty choice. CONCLUSION: Rotation type does not appear to
      affect acquisition of psychiatric knowledge as estimated by standardized
      examination scores, nor does it appear to influence students' perceptions of
      psychiatry or specialty choice.

PMID- 19398623
TI  - Uses and limitations of simulated patients in psychiatric education.
AB  - OBJECTIVES: The use of standardized patients (SPs) is becoming prominent as a
      learning and evaluation tool in both undergraduate and graduate medical
      education. As increasing attempts are made to extend this tool to psychiatric
      training and education, it has been suggested that SPs can be useful not only to
      expose students to the variety of psychopathologic states, but also to teach and
      assess complex interpersonal processes such as empathic engagement and
      psychodynamic psychotherapy. The author argues that current enthusiasm for this
      modality should be tempered with caution about its limitations. METHODS: Current
      uses of SPs in psychiatry as described in the psychiatric education and general
      medical education literature are critically reviewed. RESULTS: Inherent problems
      in the use of SPs in psychiatry are described as they relate to the nature of
      empathy and the uniquely interpersonal nature of psychiatry. CONCLUSION: SPs are
      useful additions to our educational toolbox but have intrinsic limitations for
      our field due to psychiatry's roots in the nature of empathy and the patient
      psychiatrist relationship. Standardized patients are most appropriate for
      exposing trainees to a variety of psychopathologies and testing very discrete
      skills; the use of SPs is most problematic for teaching psychotherapy and
      assessing complex interpersonal skills, such as empathic responsiveness.

PMID- 19398624
TI  - Psychiatry clerkship students' preparation, reflection, and results on the NBME
      Psychiatry Subject Exam.
AB  - OBJECTIVE: Psychiatry clerkship training involves many learning components, one
      of which is acquisition of scholarly knowledge. The authors investigate the
      reading materials and learning methods used by clinical clerks in their
      preparation for the National Board of Medical Examiners (NBME) Psychiatry Subject
      Exam (PSE). METHODS: Clerkship students from six U.S. medical schools who had
      recently completed their psychiatry clerkship and PSE were surveyed regarding
      reading material use, teaching methods encountered, and other relevant resources
      which may have influenced their PSE scores. RESULTS: The most frequently used PSE
      preparation material was a "step-or-prep" book, followed by practice questions,
      handouts, and assigned texts. No single preparation material type or combination
      proved significantly different in influencing PSE scores. The didactic methods
      used in clerkships did differ significantly in their influence on PSE scores.
      Students in the top quartile used slightly more books and different combinations
      of books than students in the bottom quartile. CONCLUSION: Students exhibited
      several trends in their preparation for the PSE. The most striking findings were
      the heavy student reliance on step-or-prep books over other learning resources
      and that step-or-prep books did not demonstrate significance as a superior
      preparation resource for the PSE. These trends in third-year psychiatric
      rotations have important implications for medical student education.

PMID- 19398625
TI  - Teaching the physician-manager role to psychiatric residents: development and
      implementation of a pilot curriculum.
AB  - OBJECTIVE: The authors describe a pilot physician-manager curriculum designed to
      address the learning needs of psychiatric residents in administrative psychiatry
      and health systems. METHODS: The pilot curriculum includes a junior and a senior
      toolkit of four workshops each. The junior toolkit introduces postgraduate-year
      two (PGY-2) residents to the principles of teamwork, conflict resolution, quality
      improvement, and program planning and evaluation. The senior toolkit exposes PGY
      4 residents to leadership and change management, organizational structures,
      mental health and addictions reform, and self and career development. Following
      curriculum implementation at the University of Toronto, residents rated the
      importance and clinical relevance of curriculum objectives and commented on the
      strengths and weaknesses of the workshops and areas needing improvement. RESULTS:
      The pilot curriculum was successfully introduced at the University of Toronto in
      2006. Residents rated the curriculum very highly and commented that interactive
      learning and contextually relevant topics are essential in meeting their needs.
      CONCLUSION: It is possible to successfully introduce a physician-manager
      curriculum early during psychiatric residency training, to match the specific
      needs of clinical rotations. Interactive techniques and clinical illustrations
      may be crucial in facilitating teaching and learning the physician-manager role.
      The authors discuss barriers, facilitators, and critical success factors in
      implementing such a curriculum.

PMID- 19398626
TI  - Preparing psychiatric residents for the "real world": a practice management
      curriculum.
AB  - OBJECTIVE: The authors describe a course designed for residents to develop the
      knowledge and skills necessary to collaborate and successfully compete in today's
      complex health care environment and to achieve competency in systems-based
      practice. METHODS: Postgraduation surveys demonstrated a need for improvement in
      preparing residents for practice management issues. The authors outline a 32-week
      practice management curriculum for postgraduate-year 3 (PGY 3) psychiatric
      residents. RESULTS: The course was rated highly by residents in terms of topics
      covered, faculty involvement, and overall expectations. The project assignments
      completed by the residents were effective in creating objective change in the
      resident outpatient practice. CONCLUSION: Practice management is an essential
      part of residency training and can be successfully integrated into the residents'
      clinical practice experience. Future steps include assessment of the graduates at
      1 and 5 years postgraduation to evaluate the long-term efficacy of the course.

PMID- 19398627
TI  - Teaching residents practice-management knowledge and skills: an in vivo
      experience.
AB  - OBJECTIVE: This article explores the relevant data regarding teaching psychiatric
      residents practice management knowledge and skills. This article also introduces
      a unique program for teaching practice management to residents. METHODS: A
      literature search was conducted through PubMed and Academic Psychiatry.
      Additionally residents involved in the training program for practice management
      were given an anonymous survey to complete. RESULTS: There were no randomized,
      controlled trials in the academic psychiatric field concerning the topic of
      practice management. The responses to the resident survey (n=10) indicated a
      modest improvement in residents' perception of receiving adequate training and
      exposure to practice management knowledge and skills. CONCLUSIONS: The available
      research suggests that many residents and faculty believe that practice
      management knowledge and skills are still not adequately addressed. The Baylor
      Clinic practice management program may be one possible solution for integrating
      the teaching of practice management knowledge and skills. More research on this
      topic is needed.

PMID- 19398628
TI  - What do psychiatric residents think of addiction psychiatry as a career?
AB  - OBJECTIVE: The authors attempt to better understand the recent decline in the
      number of applicants to addiction psychiatry training. METHODS: The Corresponding
      Committee on Training and Education in Addiction Psychiatry of APA's Council on
      Addiction Psychiatry sent out a 14-question anonymous e-mail survey to all
      postgraduate-year 2 (PGY-2) through PGY-4 APA Members-in-Training. The questions
      explored residents' beliefs and attitudes toward addiction psychiatry and sought
      their opinion on how training in addiction psychiatry can be made more attractive
      to them. RESULTS: Of 2,511 eligible psychiatric residents surveyed nationally,
      276 (10.6%) residents responded to the survey. Residents who responded had a
      generally positive impression of addiction psychiatrists but expressed much less
      favorable attitudes toward the practice of addiction psychiatry. Respondents
      provided three major subsets of suggestions: employment security and
      compensation, optimize PGY-1-4 addiction training, and fellowship training
      issues. CONCLUSION: These findings may be used to improve addiction psychiatry
      training and recruitment.

PMID- 19398629
TI  - Integrating case topics in medical school curriculum to enhance multiple skill
      learning: using fetal alcohol spectrum disorders as an exemplary case.
AB  - OBJECTIVES: This article describes the use of fetal alcohol spectrum disorders
      (FASDs) as a theme to connect the learning of basic neurosciences with clinical
      applications across the age span within a systems-based, integrated curricular
      structure that emphasizes problem-based learning. METHODS: In collaboration with
      the Centers for Disease Control and Prevention (CDC) and the National
      Organization on Fetal Alcohol Syndrome, the Western Regional Training Center for
      Fetal Alcohol Exposure at UCLA developed and integrated educational materials on
      FASDs into the curriculum for first-year medical students. RESULTS: Quantitative
      and qualitative evaluations suggested materials were effective in enhancing
      student knowledge and skills related to FASDs, as well as embryology, brain
      development, substance abuse, developmental psychopathology, and medical ethics.
      CONCLUSION: The use of a unifying theme integrating basic science and clinical
      information and skills is effective for medical student training in the
      prevention and treatment of common medical problems.

PMID- 19398630
TI  - Usefulness of psychiatric grand rounds for medical student education.
AB  - OBJECTIVE: The author studies medical students' perception of the educational
      value of weekly psychiatric grand rounds and attempts to clarify whether their
      specific needs should be considered in planning the program. METHODS: Student and
      non-student responses to four relevant items on a 16-item questionnaire were
      compared to identify differences in the perceptions of educational quality,
      degree to which objectives were met, current relevance, and future usefulness of
      content as reference tool. RESULTS: The author compared approximately 270 general
      audience responses and 83 student responses to the selected items for 19 grand
      round presentations in the last academic year. Overall, both groups rated the
      educational quality of the presentations and the degree to which the speakers
      achieved their stated objectives equally. The two groups differed, however, on
      the relevance of the topics and the potential value of the content for future
      use. CONCLUSION: The two groups rated the educational quality of the
      presentations equally favorably despite differences in the perceived current
      relevance and future value, which suggests that there is no significant need for
      program change.

PMID- 19398631
TI  - Impact on psychiatric interns of watching live electroconvulsive treatment.
AB  - OBJECTIVE: Watching a live electroconvulsive treatment (ECT) has both positive
      and negative effects on spectators. The authors aim to survey the attitude change
      towards ECT in interns after watching a live ECT session. METHODS: A 23-item
      questionnaire was administered to 66 interns before and after watching ECT.
      RESULTS: In five statements, the number of answers indicating negative attitudes
      decreased significantly after viewing ECT. A general change in attitude towards
      ECT depended on the interns' knowledge about the treatment. In the group of
      interns claiming minimal knowledge about ECT, a positive attitude change toward
      ECT and an increase in the acceptance of ECT were found, while in the group with
      moderate self-rated knowledge no significant attitude change, but a decrease in
      acceptance, were detected. CONCLUSION: The visual information on ECT reduced the
      interns' negative attitudes, in general; however, acceptance of the treatment
      decreased in a subgroup of interns.

PMID- 19398633
TI  - M.D. faculty salaries in psychiatry and all clinical science departments, 1980
      2006.
AB  - OBJECTIVE: The authors compare trends in the salaries of physician faculty in
      academic departments of psychiatry with those of physician faculty in all
      academic clinical science departments from 1980-2006. METHODS: The authors
      compared trend lines for psychiatry and all faculty by academic rank, including
      those for department chairs, by graphing inflation-adjusted (2006 dollars)
      Association of American Medical Colleges Faculty Survey data over the 27-year
      span and computing compound annual growth rates. RESULTS: Physician faculty
      salaries in both psychiatry and all departments increased between 1980 and 2006.
      Compared with salaries for physician faculty in all specialties, those for
      psychiatrists were lower and the trend lines were flatter. Salary gaps between
      chairs and professors increased considerably in all faculty and psychiatry
      departments. CONCLUSION: Salaries for academic physicians are rising, and they
      are keeping pace with inflation. Relatively large and growing gaps exist between
      psychiatry and all faculty and between chairs and professors in both psychiatry
      and all clinical sciences departments.

PMID- 19398634
TI  - Three-session psychiatric malpractice curriculum for senior psychiatry residents.

PMID- 19398635
TI  - The Chief Resident for Education: description of a novel academic teaching
      position.

PMID- 19398636
TI  - Speaking out for mental health: collaboration of future journalists and
      psychiatrists.
AB  - OBJECTIVES: The authors assess the effects of an educational intervention on the
      attitudes and understanding of psychiatric residents and journalism students,
      review how collaboration between these disciplines affects these attitudes, and
      propose the development of similar programs within residency to enhance systems
      based learning. METHODS: A collaborative curriculum involving a workshop,
      didactics, and team projects was conducted over 6 months among journalism
      students and psychiatric residents. Attitude assessments were obtained before and
      at the conclusion. RESULTS: Data support that a brief interdisciplinary
      curriculum can affect the attitudes of both psychiatric residents and journalism
      students regarding mental illness and the media. Attitudinal changes and areas of
      focus for the future are identified. CONCLUSION: Psychiatrists should be familiar
      with the relationship between media and stigma. Focusing on psychiatrists and
      journalists in training may change attitudes between disciplines to promote
      future collaboration, and innovative curricula within residency training may
      increase the comfort level between physicians and the media.

PMID- 19398637
TI  - Factors determining satisfaction in psychiatry training in Israel.
AB  - OBJECTIVES: The authors aim to identify the most important factors for Israeli
      residents in determining their satisfaction with psychiatric training programs
      and to compare the findings with similar U.S. data. METHODS: One hundred sixty
      Israeli psychiatric residents were asked to complete a 40-item questionnaire
      indicating the relative importance of these items in determining their
      satisfaction with training on a five-point Likert scale. RESULTS: A total of 100
      residents from 15 programs completed the survey. The authors composed a list of
      the 10 most important items in determining Israeli residents' satisfaction with
      psychiatric training. "Quality of supervision" and "respect of faculty for
      residents" were the most important items on this list. These items were ranked
      significantly higher than all the rest of the items. The authors identified some
      significant differences between subgroups of the Israeli residents, namely the
      Israeli and international medical graduates. The list of the most important items
      for Israeli residents was found to be very similar to published findings for U.S.
      residents. CONCLUSION: Program directors should consider this list of most
      important items in determining resident satisfaction, especially the domains of
      educational opportunities and educational ambiance, when attempting to improve
      training programs.

PMID- 19398638
TI  - Facing wolves.

PMID- 19398640
TI  - Pharmacological exploitation of an off-target antibacterial effect of the
      cyclooxygenase-2 inhibitor celecoxib against Francisella tularensis.
AB  - Francisella tularensis, a bacterium which causes tularemia in humans, is
      classified as a CDC category A bioterrorism agent. In this study, we demonstrate
      that celecoxib, an anti-inflammatory cyclooxygenase-2 inhibitor in clinical use,
      exhibits activity against a type A strain of F. tularensis (Schu S4), the live
      vaccine strain of F. tularensis (a type B strain), and F. novicida ("F.
      tularensis subsp. novicida") directly in growth medium. This bacterial killing,
      however, was not noted with rofecoxib, despite its higher potency than that of
      celecoxib in inhibiting cyclooxygenase-2. The unique ability of celecoxib to
      inhibit the proliferation of F. tularensis could be pharmacologically exploited
      to develop novel anti-Francisella therapeutic agents, of which the proof of
      principle is demonstrated by compound 20, a celecoxib derivative identified
      through the screening of a celecoxib-based focused compound library. Compound 20
      inhibited the intracellular proliferation of Francisella in macrophages without
      causing appreciable toxicity to these host cells. Together, these data support
      the translational potential of compound 20 for the further development of novel,
      potent anti-Francisella agents.

PMID- 19398641
TI  - Nine-hospital study comparing broth microdilution and Etest method results for
      vancomycin and daptomycin against methicillin-resistant Staphylococcus aureus.
AB  - Vancomycin and daptomycin MIC results for 1,800 randomly selected oxacillin
      (methicillin [meticillin])-resistant Staphylococcus aureus (MRSA) bloodstream
      isolates from nine U.S. hospitals (collected from 2002 to 2006) were determined
      by a reference broth microdilution (BMD) method using frozen-form panels with
      precise incremental dilutions and by the Etest technique. The Etest provided
      vancomycin and daptomycin MIC results that were consistently higher (0.5 to 1.5
      log(2) dilution steps) than those provided by the reference BMD method. The
      dominant MRSA population (91.2% of MRSA isolates) would be categorized as
      vancomycin nonsusceptible by the MIC results from the Etest method if the
      susceptibility breakpoint was adjusted downward to < or =1 microg/ml, as
      suggested by clinical outcome studies.

PMID- 19398642
TI  - GS-9191 is a novel topical prodrug of the nucleotide analog 9-(2
      phosphonylmethoxyethyl)guanine with antiproliferative activity and possible
      utility in the treatment of human papillomavirus lesions.
AB  - GS-9191 is a novel double prodrug of the nucleotide analog 9-(2
      phosphonylmethoxyethyl)guanine (PMEG) designed as a topical agent to permeate
      skin and be metabolized to the active nucleoside triphosphate analog in the
      epithelial layer. The prodrug was shown to be metabolized intracellularly to 9-(2
      phosphonylmethoxyethyl)-N(6)-cyclopropyl-2,6,diaminopurine (cPrPMEDAP) and
      subsequently deaminated to PMEG. The active form, PMEG diphosphate, was shown to
      be a potent inhibitor of DNA polymerase alpha and beta while showing weaker
      activity against mitochondrial DNA polymerase gamma (50% enzyme inhibition
      observed at 2.5, 1.6, and 59.4 microM, respectively). GS-9191 was markedly more
      potent than PMEG or cPrPMEDAP in a series of human papillomavirus (HPV)-positive
      cell lines, with effective concentrations to inhibit 50% cell growth (EC(50)) as
      low as 0.03, 207, and 284 nM, respectively. In contrast, GS-9191 was generally
      less potent in non-HPV-infected cells and primary cells (EC(50)s between 1 and 15
      nM). DNA synthesis was inhibited by GS-9191 within 24 h of treatment; cells were
      observed to be arrested in S phase by 48 h and to subsequently undergo apoptosis
      (between 3 and 7 days). In an animal model (cottontail rabbit papillomavirus),
      topical GS-9191 was shown to decrease the size of papillomas in a dose-related
      manner. At the highest dose (0.1%), cures were evident at the end of 5 weeks, and
      lesions did not recur in a 30-day follow-up period. These data suggest that GS
      9191 may have utility in the treatment of HPV-induced lesions.

PMID- 19398643
TI  - Effect of tipranavir-ritonavir on pharmacokinetics of raltegravir.
AB  - Raltegravir (RAL) is a novel and potent human immunodeficiency virus type 1
      integrase inhibitor that is predominantly metabolized via glucuronidation. The
      protease inhibitor combination tipranavir (TPV) at 500 mg and ritonavir (RTV) at
      200 mg (TPV-RTV) has inhibitory and inductive effects on metabolic enzymes, which
      includes the potential to induce glucuronosyltransferase. Because RAL may be
      coadministered with TPV-RTV, there is the potential for the induction of RAL
      metabolism. Consequently, we assessed the effect of TPV-RTV on the
      pharmacokinetics of RAL and the safety and tolerability of this combination.
      Eighteen healthy adults were enrolled in this open-label study. The participants
      received RAL at 400 mg twice daily for 4 days (period 1) and TPV-RTV twice daily
      for 7 days (period 2), followed immediately by 400 mg RAL with TPV-RTV twice
      daily for 4 days (period 3). Under steady-state conditions, the RAL concentration
      at 12 h (C(12)) was decreased when RAL was administered with TPV-RTV (geometric
      mean ratio [GMR], 0.45; 90% confidence interval [CI] 0.31, 0.66; P = 0.0021);
      however, the area under the concentration-time curve from time zero to 12 h (GMR,
      0.76; 90% CI, 0.49, 1.19; P = 0.2997) and the maximum concentration in serum
      (GMR, 0.82; 90% CI, 0.46, 1.46; P = 0.5506) were not substantially affected.
      There were no serious adverse experiences or discontinuations due to study drug
      related adverse experiences, and RAL coadministered with TPV-RTV was generally
      well tolerated. Although the RAL C(12) was decreased with TPV-RTV in this study,
      favorable efficacy data collected in phase III studies substantiate that TPV-RTV
      may be coadministered with RAL without dose adjustment.

PMID- 19398644
TI  - Integration of pharmacokinetic and pharmacodynamic indices of orbifloxacin in
      beagle dogs after a single intravenous and intramuscular administration.
AB  - The pharmacokinetics (PK) and pharmacodynamics (PD) of orbifloxacin were studied
      in beagle dogs after intravenous (i.v.) and intramuscular (i.m.) administration
      at a dose of 2.5 mg/kg body weight. An absolute bioavailability of 100.1% +/-
      4.76%, a terminal half-life of 4.23 +/- 0.2 h and 3.95 +/- 0.15 h after i.v. and
      i.m. administration, a steady-state volume of distribution of 1.61 +/- 0.13
      liters/kg, and clearance of 0.31 +/- 0.03 liters/h/kg were observed. Orbifloxacin
      showed rapid, concentration-dependent killing against the Escherichia coli,
      Staphylococcus aureus, Staphylococcus intermedius, and Proteus mirabilis clinical
      isolates. Computations based on PK-PD analysis indicated that the recommended
      dose is unlikely to be clinically effective against some strains like S.
      intermedius. Therefore, a higher dose of orbifloxacin would be worthy of
      consideration for treatment of certain bacterial infections in dogs.

PMID- 19398645
TI  - Effects of cranberry juice on pharmacokinetics of beta-lactam antibiotics
      following oral administration.
AB  - Cranberry juice consumption is often recommended along with low-dose oral
      antibiotics for prophylaxis for recurrent urinary tract infection (UTI). Because
      multiple membrane transporters are involved in the intestinal absorption and
      renal excretion of beta-lactam antibiotics, we evaluated the potential risk of
      pharmacokinetic interactions between cranberry juice and the beta-lactams
      amoxicillin (amoxicilline) and cefaclor. The amoxicillin-cranberry juice
      interaction was investigated in 18 healthy women who received on four separate
      occasions a single oral test dose of amoxicillin at 500 mg and 2 g with or
      without cranberry juice cocktail (8 oz) according to a crossover design. A
      parallel cefaclor-cranberry juice interaction study was also conducted in which
      500 mg cefaclor was administered with or without cranberry juice cocktail (12
      oz). Data were analyzed by noncompartmental methods and nonlinear mixed-effects
      compartmental modeling. We conclude that the concurrent use of cranberry juice
      has no significant effect on the extent of oral absorption or the renal clearance
      of amoxicillin and cefaclor. However, delays in the absorption of amoxicillin and
      cefaclor were observed. These results suggest that the use of cranberry juice at
      usual quantities as prophylaxis for UTI is not likely to alter the
      pharmacokinetics of these two oral antibiotics.

PMID- 19398646
TI  - In vitro elution of daptomycin by a synthetic crystallic semihydrate form of
      calcium sulfate, stimulan.
AB  - A synthetic crystallic semihydrate form of calcium sulfate, Stimulan, was
      evaluated as a biodegradable carrier for the daily in vitro elution of
      daptomycin. Daptomycin and Stimulan were admixed at a ratio of 95:5. Elution
      lasted for 28 days. Eluted concentrations peaked on days 1 and 11, when the mean
      values were 1,320.1 and 949.2 microg/ml, respectively. The lowest eluted
      concentration was detected on day 28. These results support the application of
      the system described in experimental models of osteomyelitis.

PMID- 19398647
TI  - Characterization of cefoxitin-resistant Escherichia coli isolates from
      recreational beaches and private drinking water in Canada between 2004 and 2006.
AB  - A total of 142 cefoxitin-resistant Escherichia coli isolates from water sources
      were collected across Canada. Multidrug resistance was observed in 65/142 (45.8%)
      isolates. The bla(CMY-2) gene was identified in 110/142 (77.5%) isolates.
      Sequencing of the chromosomal ampC promoter region showed mutations from the wild
      type, previously shown to hyperproduce AmpC. CMY-2-producing plasmids
      predominantly belonged to replicon groups I1-Igamma, A/C, and K/B. The majority
      of the E. coli isolates belonged to the nonvirulent phylogenetic groups A and B1.

PMID- 19398648
TI  - Alkoxyalkyl esters of 9-(s)-(3-hydroxy-2-phosphonomethoxypropyl) adenine are
      potent and selective inhibitors of hepatitis B virus (HBV) replication in vitro
      and in HBV transgenic mice in vivo.
AB  - Alkoxyalkyl esters of acyclic nucleoside phosphonates have previously been shown
      to have increased antiviral activity when they are administered orally in animal
      models of viral diseases, including lethal infections with vaccinia virus, cowpox
      virus, ectromelia virus, murine cytomegalovirus, and adenovirus. 9-(S)-(3-Hydroxy
      2-phosphonomethoxypropyl)adenine [(S)-HPMPA] was previously shown to have
      activity against hepatitis B virus (HBV) in vitro. To assess the effect of
      alkoxyalkyl esterification of (S)-HPMPA, we prepared the hexadecyloxypropyl
      (HDP), 15-methyl-hexadecyloxypropyl (15M-HDP), and octadecyloxyethyl (ODE) esters
      and compared their activities with the activity of adefovir dipivoxil in vitro
      and in vivo. Alkoxyalkyl esters of (S)-HPMPA were 6 to 20 times more active than
      unmodified (S)-HPMPA on the basis of their 50% effective concentrations in 2.2.15
      cells. The increased antiviral activity appeared to be due in part to the
      increased uptake and conversion of HDP-(S)-HPMPA to HPMPA diphosphate observed in
      HepG2 cells in vitro. HDP-(S)-HPMPA retained full activity against HBV mutants
      resistant to lamivudine (L180M, M204V), but cross-resistance to a mutant
      resistant to adefovir (N236T) was detected. HDP-(S)-HPMPA is orally bioavailable
      and provides excellent liver exposure to the drug. Oral treatment of HBV
      transgenic mice with HDP-(S)-HPMPA, 15M-HDP-(S)-HPMPA, and ODE-(S)-HPMPA for 14
      days reduced liver HBV DNA levels by roughly 1.5 log units, a response equivalent
      to that of adefovir dipivoxil.

PMID- 19398649
TI  - Epidemic clonal groups of Escherichia coli as a cause of antimicrobial-resistant
      urinary tract infections in Canada, 2002 to 2004.
AB  - The extent to which clonal spread contributes to emerging antimicrobial
      resistance in Escherichia coli is incompletely defined. To address this question
      within a recent, nationally representative strain collection, three established
      drug-resistant E. coli clonal groups (i.e., clonal group A, E. coli O15:K52:H1,
      and sequence type 131 [ST131]) were sought among 199 E. coli urine isolates
      recovered from across Canada from 2002 to 2004, with stratification by resistance
      to trimethoprim-sulfamethoxazole (TS) and fluoroquinolones (FQs). The isolates'
      clonal backgrounds, virulence genotypes, and macrorestriction profiles were
      assessed. The three clonal groups were found to account for 37.2% of isolates
      overall, but accounted for 0% of TS-susceptible (TS-S) and FQ-susceptible (FQ-S)
      isolates, 20% of TS-resistant (TS-R) and FQ-S isolates, 60% of TS-S and FQ-R
      isolates, and 68% of TS-R and FQ-R isolates (P < 0.001). E. coli ST131, the most
      prevalent clonal group, accounted for 23.1% of isolates overall and for 44% of
      the FQ-R isolates. Nearly all ST131 isolates were FQ-R (96%) but, notably,
      cephalosporin susceptible (98%). Although the distinctive virulence profiles of
      the FQ-R clonal group isolates were less extensive than those of the susceptible
      isolates, they were significantly more extensive than those of the other FQ-R
      isolates. These findings indicate that among the E. coli urine isolates studied,
      resistance to TS and FQs has a prominent clonal component, with the O15:K52:H1
      clonal group and especially E. coli ST131 being the major contributors. These
      clonal groups appear to be more virulent than comparably resistant isolates,
      possibly contributing to their success as emerging multi-drug-resistant
      pathogens.

PMID- 19398650
TI  - Metabolic dysfunction in primary aldosteronism.

PMID- 19398651
TI  - Blood pressure lowering effects of a new long-acting inhibitor of
      phosphodiesterase 5 in patients with mild to moderate hypertension.
AB  - Inhibition of phosphodiesterase 5 is an attractive candidate mechanism for blood
      pressure (BP) lowering. In this study, a novel long-acting phosphodiesterase 5
      inhibitor, PF-00489791, was evaluated in 133 patients with mild to moderate
      hypertension, randomized into 1 of 4 groups: placebo, 4 mg, 10 mg, and 20 mg
      titrated after 14 days of dosing to 40 mg. Study medication was administered once
      daily for 28 days. Ambulatory BP monitoring was used. There was a statistically
      significant decrease (compared with placebo) in mean daytime systolic BP on day
      28 at the 10 and 20/40 mg doses (by approximately 5 and approximately 7 mm Hg,
      respectively). Changes in mean daytime diastolic BP corresponded with those in
      systolic BP. The magnitude of BP lowering was greater on day 1 than on days 14
      and 28, but the response was sustained between days 14 and 28. PF-00489791 also
      exerted BP lowering effects on mean 24-hour ambulatory BP. There was a dose
      related increase in plasma cGMP concentration (statistically significant at the
      20/40 mg dose). There was an increased incidence of headaches at the 10 and 20/40
      mg doses (22% and 21%, respectively, compared with 12% with placebo) and an
      increased incidence of dyspepsia/gastroesophageal reflux disease and
      musculoskeletal adverse events at the 20/40 mg dose. In conclusion, PF-00489791
      causes a clinically meaningful and sustained BP lowering in patients with
      hypertension. It is generally safe and well tolerated at the clinically
      efficacious doses.

PMID- 19398652
TI  - Influence of the menstrual cycle, pregnancy, and preeclampsia on arterial
      stiffness.
AB  - Arterial stiffness and compliance are major predictors of adverse cardiovascular
      events and are influenced by female sex hormones, including estrogen and
      progesterone. The aim of this longitudinal study was to evaluate the effect of
      the menstrual cycle, normal pregnancy, and preeclampsia on central and systemic
      arterial stiffness. Ten healthy nulliparous women with regular menses were
      studied in the early and midfollicular, periovulatory, and luteal phases of a
      single menstrual cycle. Twenty-two primigravida pregnant women were studied
      throughout pregnancy at 16, 24, 32, and 37 weeks gestation and at 7 weeks
      postpartum. Fifteen primigravida women with preeclampsia were studied at
      diagnosis and 7 weeks postpartum. Augmentation index and carotid-radial and
      carotid-femoral pulse wave velocities were measured using applanation tonometry.
      Augmentation index fell during the luteal phase of the menstrual cycle (luteal
      phase versus periovulatory phase; P<0.05). In normal pregnancy, pulse wave
      velocity and augmentation index increased from 24 weeks over the third trimester
      (P<or=0.01 for both). All of the measures were increased in women with
      preeclampsia (P<or=0.01), with augmentation index and carotid-femoral pulse wave
      velocity remaining elevated 7 weeks postpartum (P<or=0.02). We conclude that
      systemic arterial stiffness undergoes major changes during the menstrual cycle
      and pregnancy and that preeclampsia is associated with greater and more prolonged
      increases in arterial stiffness. These effects may contribute to adverse
      cardiovascular outcomes of pregnancy and preeclampsia.

PMID- 19398653
TI  - Tetrahydrobiopterin, endothelial nitric oxide synthase, and mitochondrial
      function in the heart.

PMID- 19398654
TI  - Taurine: red bull or red herring?

PMID- 19398656
TI  - High dietary taurine reduces apoptosis and atherosclerosis in the left main
      coronary artery: association with reduced CCAAT/enhancer binding protein
      homologous protein and total plasma homocysteine but not lipidemia.
AB  - We sought to determine whether taurine could specifically protect against
      coronary artery disease during an atherogenic diet and whether taurine affects
      the lipid profile, metabolites of methionine, and endothelial atherogenic
      systems. Rabbits were fed one of the following diets for 4 weeks: (1) control
      diet; (2) 0.5% cholesterol+1.0% methionine; or (3) 0.5% cholesterol+1.0%
      methionine+2.5% taurine. Endothelial function was examined, and the left main
      coronary artery atherosclerosis was quantified by stereology and semiquantitative
      immunohistochemistry to determine the endothelial expression of proteins related
      to the NO, renin-angiotensin, endoplasmic reticulum, and oxidative stress
      systems, as well as apoptosis. Taurine normalized hyperhomocysteinemia (P<0.05)
      and significantly reduced hypermethioninemia (P<0.05) but not lipidemia. The
      intima:media ratio was reduced by 28% (P=0.034), and atherosclerosis was reduced
      by 64% (P=0.012) and endothelial cell apoptosis by 30% (P<0.01). Endothelial cell
      CCAAT/enhancer binding protein homologous protein was normalized (P<0.05).
      Taurine failed to improve hyperlipidemia, endothelial function, or endothelial
      proteins related to the NO, renin-angiotensin, and oxidative stress systems.
      Taurine reduces left main coronary artery wall pathology associated with
      decreased plasma total homocysteine, methionine, apoptosis, and normalization of
      CCAAT/enhancer binding protein homologous protein. These results elucidate the
      antiapoptotic and antiatherogenic properties of taurine, possibly via
      normalization of endoplasmic reticulum stress.

PMID- 19398655
TI  - Mitochondria and reactive oxygen species.

PMID- 19398657
TI  - The (F)low down on the endothelial epithelial sodium channel: epithelial sodium
      channel as a brake on flow-mediated vasodilation.

PMID- 19398658
TI  - Mitochondrial transfer RNAMet 4435A>G mutation is associated with maternally
      inherited hypertension in a Chinese pedigree.
AB  - Mitochondrial DNA mutations have been associated with cardiovascular disease. We
      report here the clinical, genetic, and molecular characterization of 1 Han
      Chinese family with suggestively maternally transmitted hypertension. Matrilineal
      relatives in this family exhibited the variable degree of hypertension at the age
      at onset of 44 to 55 years old. Sequence analysis of entire mitochondrial DNA in
      this pedigree identified the known homoplasmic 4435A>G mutation, which is located
      immediately at the 3 prime end to the anticodon, corresponding with the
      conventional position 37 of tRNA(Met), and 35 other variants belonging to the
      Asian haplogroup B5a. The adenine (A37) at this position of tRNA(Met) is
      extraordinarily conserved from bacteria to human mitochondria. This modified A37
      was shown to contribute to the high fidelity of codon recognition, the structural
      formation, and stabilization of functional tRNAs. In fact, a 40% reduction in the
      levels of tRNA(Met) was observed in cells carrying the 4435A>G mutation. As a
      result, a failure in mitochondrial tRNA metabolism, caused by the 4435A>G
      mutation, led to approximately 30% reduction in the rate of mitochondrial
      translation. However, the homoplasmic form, mild biochemical defect, and late
      onset of hypertension in subjects carrying the 4435A>G mutation suggest that the
      4435A>G mutation itself is insufficient to produce a clinical phenotype. The
      other modifier factors, such as nuclear modifier genes, environmental, and
      personal factors may also contribute to the development of hypertension in the
      subjects carrying this mutation. Our findings imply that the 4435A>G mutation may
      act as an inherited risk factor for the development of hypertension in this
      Chinese pedigree.

PMID- 19398659
TI  - Endothelial epithelial sodium channel inhibition activates endothelial nitric
      oxide synthase via phosphoinositide 3-kinase/Akt in small-diameter mesenteric
      arteries.
AB  - Recent studies have shown that the epithelial sodium channel (ENaC) is expressed
      in vascular tissue. However, the role that ENaC may play in the responses to
      vasoconstrictors and NO production has yet to be addressed. In this study, the
      contractile responses of perfused pressurized small-diameter rat mesenteric
      arteries to phenylephrine and serotonin were reduced by ENaC blockade with
      amiloride (75.1+/-3.2% and 16.9+/-2.3% of control values, respectively; P<0.01)
      that was dose dependent (EC(50)=88.9+/-1.6 nmol/L). Incubation with benzamil,
      another ENaC blocker, had similar effects. alpha, beta, and gamma ENaC were
      identified in small-diameter rat mesenteric arteries using RT-PCR and Western
      blot with specific antibodies. In situ hybridization and immunohistochemistry
      localized ENaC expression to the tunica media and endothelium of small-diameter
      rat mesenteric arteries. Patch-clamp experiments demonstrated that primary
      cultures of mesenteric artery endothelial cells expressed amiloride-sensitive
      sodium currents. Mechanical ablation of the endothelium or inhibition of eNOS
      with N(omega)-nitro-L-arginine inhibited the reduction in contractility caused by
      ENaC blockers. ENaC inhibitors increased eNOS phosphorylation (Ser 1177) and Akt
      phosphorylation (Ser 473). The presence of the phosphoinositide 3-kinase
      inhibitor LY294002 blunted Akt phosphorylation and eNOS phosphorylation and the
      decrease in the response to phenylephrine caused by blockers of ENaC, indicating
      that the phosphoinositide 3-kinase/Akt pathway was activated after ENaC
      inhibition. Finally, we observed that the effects of blockers of ENaC were flow
      dependent and that the vasodilatory response to shear stress was enhanced by ENaC
      blockade. Our results identify a previously unappreciated role for ENaC as a
      negative modulator of eNOS and NO production in resistance arteries.

PMID- 19398660
TI  - Free leptin is associated with masked hypertension in nonobese subjects: a cross
      sectional study.
AB  - The aim of the study was to investigate whether diverse clinical blood pressure
      phenotypes are associated with free leptin surrogates, as reflected by plasma
      leptin, human soluble leptin receptor, and their ratio (ie, free leptin index) in
      nonobese normoglycemic subjects. Three separate clinic blood pressure
      measurements and ambulatory blood pressure monitoring were implemented to divide
      494 subjects (aged 44+/-5 years; 272 men; body mass index: <30 kg/m(2)) into
      hypertensives (n=166), white-coat hypertensives (n=82), masked hypertensives
      (n=66), and normotensives (n=180). Participants underwent echocardiography,
      while, from fasting venous blood samples, metabolic profile, plasma leptin, and
      its receptor levels were assessed. Hypertensives and masked hypertensives
      demonstrated higher levels of log (10)(leptin) and log (10)(free leptin index),
      as well as lower levels of log (10)(human soluble leptin receptor) with respect
      to normotensives. White-coat hypertensives had similar free leptin surrogates
      compared with normotensives. Younger age, 24-hour systolic and diastolic blood
      pressures, 24-hour heart rate, and left ventricle mass index were common
      correlates of free leptin surrogates. After adjustment for confounders, masked
      hypertensive and hypertensive with respect to normotensive phenotype were
      associated with log (10)(leptin) with odds ratios (95% CIs) of 1.31 (1.12 to
      3.80) and 1.26 (1.09 to 2.24), respectively, log (10)(human soluble leptin
      receptor) with 0.65 (0.53 to 0.78) and 0.69 (0.57 to 0.84), respectively, and log
      (10)(free leptin index) with 2.46 (1.32 to 7.23) and 1.84 (1.26 to 3.73),
      respectively (P<0.05 for all of the cases). Free leptin surrogates are associated
      with masked hypertension in nonobese normoglycemic subjects. Free leptin is
      almost equally increased in masked and sustained hypertension, suggesting a
      similar leptin-related vascular impairment.

PMID- 19398661
TI  - Metallothionein abrogates GTP cyclohydrolase I inhibition-induced cardiac
      contractile and morphological defects: role of mitochondrial biogenesis.
AB  - One key mechanism for endothelial dysfunction is endothelial NO synthase (eNOS)
      uncoupling, whereby eNOS generates O(2)(*-) rather than NO because of deficient
      eNOS cofactor tetrahydrobiopterin (BH4). This study was designed to examine the
      effect of BH4 deficiency on cardiac morphology and function, as well as the
      impact of metallothionein (MT) on BH4 deficiency-induced abnormalities, if any.
      Friend virus B (FVB) and cardiac-specific MT transgenic mice were exposed to 2,4
      diamino-6-hydroxy-pyrimidine (DAHP; 10 mmol/L, 3 weeks), an inhibitor of the BH4
      synthetic enzyme GTP cyclohydrolase I. DAHP reduced plasma BH4 levels by 85% and
      elevated blood pressure in both FVB and MT mice. Echocardiography found decreased
      fractional shortening and increased end-systolic diameter in DAHP-treated FVB
      mice. Cardiomyocytes from DAHP-treated FVB mice displayed enhanced O(2)(*-)
      production, contractile and intracellular Ca(2+) defects including depressed peak
      shortening and maximal velocity of shortening/relengthening, prolonged duration
      of relengthening, reduced intracellular Ca(2+) rise, and clearance. DAHP
      triggered mitochondrial swelling/myocardial filament aberrations and
      mitochondrial O(2)(*-) accumulation, assessed by transmission electron microscopy
      and MitoSOX Red fluorescence, respectively. DAHP also promoted the N(G)-nitro-l
      arginine methyl ester-inhibitable O(2)(*-) production and eNOS phosphorylation at
      Thr497. Although MT had little effect on cardiac mechanics and ultrastructure, it
      attenuated DAHP-induced defects in cardiac function, morphology, O(2)(*-)
      production, and eNOS phosphorylation (Thr497). The DAHP-induced cardiomyocyte
      mechanical responses were alleviated by in vitro BH4 treatment. DAHP inhibited
      mitochondrial biogenesis, mitochondrial uncoupling protein 2, and chaperone heat
      shock protein 90, and all but uncoupling protein 2 were rescued by MT. Our data
      suggest a role for BH4 deficiency in cardiac dysfunction and the therapeutic
      potential of antioxidants against eNOS uncoupling in the heart.

PMID- 19398662
TI  - Cardiac mast cells mediate left ventricular fibrosis in the hypertensive rat
      heart.
AB  - Correlative data suggest that cardiac mast cells are a component of the
      inflammatory response that is important to hypertension-induced adverse
      myocardial remodeling. However, a causal relationship has not been established.
      We hypothesized that adverse myocardial remodeling would be inhibited by
      preventing the release of mast cell products that may interact with fibroblasts
      and other inflammatory cells. Eight-week-old male spontaneously hypertensive rats
      were treated for 12 weeks with the mast cell stabilizing compound nedocromil (30
      mg/kg per day). Age-matched Wistar-Kyoto rats served as controls. Nedocromil
      prevented left ventricular fibrosis in the spontaneously hypertensive rat
      independent of hypertrophy and blood pressure, despite cardiac mast cell density
      being elevated. The mast cell protease tryptase was elevated in the spontaneously
      hypertensive rat myocardium and was normalized by nedocromil. Treatment of
      isolated adult spontaneously hypertensive rat cardiac fibroblasts with tryptase
      induced collagen synthesis and proliferation, suggesting this as a possible
      mechanism of mast cell-mediated fibrosis. In addition, nedocromil prevented
      macrophage infiltration into the ventricle. The inflammatory cytokines interferon
      gamma and interleukin (IL)-4 were increased in the spontaneously hypertensive rat
      and normalized by nedocromil, whereas IL-6 and IL-10 were decreased in the
      spontaneously hypertensive rat, with nedocromil treatment normalizing IL-6 and
      increasing IL-10 above the control. These results demonstrate for the first time
      a causal relationship between mast cell activation and fibrosis in the
      hypertensive heart. Furthermore, these results identify several mechanisms,
      including tryptase, inflammatory cell recruitment, and cytokine regulation, by
      which mast cells may mediate hypertension-induced left ventricular fibrosis.

PMID- 19398663
TI  - Matrix metalloproteinase-7 and ADAM-12 (a disintegrin and metalloproteinase-12)
      define a signaling axis in agonist-induced hypertension and cardiac hypertrophy.
AB  - BACKGROUND: Excessive stimulation of Gq protein-coupled receptors by cognate
      vasoconstrictor agonists induces a variety of cardiovascular processes, including
      hypertension and hypertrophy. Here, we report that matrix metalloproteinase-7
      (MMP-7) and a disintegrin and metalloproteinase-12 (ADAM-12) form a novel
      signaling axis in these processes. METHODS AND RESULTS: In functional studies, we
      targeted MMP-7 in rodent models of acute, long-term, and spontaneous hypertension
      by 3 complementary approaches: (1) Pharmacological inhibition of activity, (2)
      expression knockdown (by antisense oligodeoxynucleotides and RNA interference),
      and (3) gene knockout. We observed that induction of acute hypertension by
      vasoconstrictors (ie, catecholamines, angiotensin II, and the nitric oxide
      synthase inhibitor N(G)-nitro-l-arginine methyl ester) required the
      posttranscriptional activation of vascular MMP-7. In spontaneously hypertensive
      rats, knockdown of MMP-7 (by RNA interference) resulted in attenuation of
      hypertension and stopped development of cardiac hypertrophy. Quantitative reverse
      transcription polymerase chain reaction studies in mouse models of MMP-7
      knockdown (by RNA interference) and gene knockout revealed that MMP-7 controlled
      the transcription of ADAM-12, the major metalloproteinase implicated in cardiac
      hypertrophy. In mice with angiotensin II-induced hypertension and cardiac
      hypertrophy, myocardial ADAM-12 and downstream hypertrophy marker genes were
      overexpressed. Knockdown of MMP-7 attenuated hypertension, inhibited ADAM-12
      overexpression, and prevented cardiac hypertrophy. CONCLUSIONS: Agonist signaling
      of both hypertension and hypertrophy depends on posttranscriptional and
      transcriptional mechanisms that involve MMP-7, which is transcriptionally
      connected with ADAM-12. Approaches targeting this novel MMP-7/ADAM-12 signaling
      axis could have generic therapeutic potential in hypertensive disorders caused by
      multiple or unknown agonists.

PMID- 19398664
TI  - Regulation of the human cardiac mitochondrial Ca2+ uptake by 2 different voltage
      gated Ca2+ channels.
AB  - BACKGROUND: Impairment of intracellular Ca(2+) homeostasis and mitochondrial
      function has been implicated in the development of cardiomyopathy. Mitochondrial
      Ca(2+) uptake is thought to be mediated by the Ca(2+) uniporter (MCU) and a thus
      far speculative non-MCU pathway. However, the identity and properties of these
      pathways are a matter of intense debate, and possible functional alterations in
      diseased states have remained elusive. METHODS AND RESULTS: By patch clamping the
      inner membrane of mitochondria from nonfailing and failing human hearts, we have
      identified 2 previously unknown Ca(2+)-selective channels, referred to as mCa1
      and mCa2. Both channels are voltage dependent but differ significantly in gating
      parameters. Compared with mCa2 channels, mCa1 channels exhibit a higher single
      channel amplitude, shorter openings, a lower open probability, and 3 to 5
      subconductance states. Similar to the MCU, mCa1 is inhibited by 200 nmol/L
      ruthenium 360, whereas mCa2 is insensitive to 200 nmol/L ruthenium 360 and
      reduced only by very high concentrations (10 micromol/L). Both mitochondrial
      Ca(2+) channels are unaffected by blockers of other possibly Ca(2+)-conducting
      mitochondrial pores but were activated by spermine (1 mmol/L). Notably, activity
      of mCa1 and mCa2 channels is decreased in failing compared with nonfailing heart
      conditions, making them less effective for Ca(2+) uptake and likely Ca(2+)
      induced metabolism. CONCLUSIONS: Thus, we conclude that the human mitochondrial
      Ca(2+) uptake is mediated by these 2 distinct Ca(2+) channels, which are
      functionally impaired in heart failure. Current properties reveal that the mCa1
      channel underlies the human MCU and that the mCa2 channel is responsible for the
      ruthenium red-insensitive/low-sensitivity non-MCU-type mitochondrial Ca(2+)
      uptake.

PMID- 19398665
TI  - Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic
      ventricular tachycardia.
AB  - BACKGROUND: The pathophysiological background of catecholaminergic polymorphic
      ventricular tachycardia is well understood, but the clinical features of this
      stress-induced arrhythmic disorder, especially the incidence and risk factors of
      arrhythmic events, have not been fully ascertained. METHODS AND RESULTS: The
      outcome in 101 catecholaminergic polymorphic ventricular tachycardia patients,
      including 50 probands, was analyzed. During a mean follow-up of 7.9 years,
      cardiac events defined as syncope, aborted cardiac arrest, including appropriate
      discharges from implantable defibrillators, or sudden cardiac death occurred in
      27 patients, including 2 mutation carriers with normal exercise tests. The
      estimated 8-year event rate was 32% in the total population and 27% and 58% in
      the patients with and without beta-blockers, respectively. Absence of beta
      blockers (hazard ratio [HR], 5.48; 95% CI, 1.80 to 16.68) and younger age at
      diagnosis (HR, 0.54 per decade; 95% CI, 0.33 to 0.89) were independent
      predictors. Fatal or near-fatal events defined as aborted cardiac arrest or
      sudden cardiac death occurred in 13 patients, resulting in an estimated 8-year
      event rate of 13%. Absence of beta-blockers (HR, 5.54; 95% CI, 1.17 to 26.15) and
      history of aborted cardiac arrest (HR, 13.01; 95% CI, 2.48 to 68.21) were
      independent predictors. No difference was observed in cardiac and fatal or near
      fatal event rates between probands and family members. CONCLUSIONS: Cardiac and
      fatal or near-fatal events were not rare in both catecholaminergic polymorphic
      ventricular tachycardia probands and affected family members during the long-term
      follow-up, even while taking beta-blockers, which was associated with a lower
      event rate. Further studies evaluating concomitant therapies are necessary to
      improve outcome in these patients.

PMID- 19398666
TI  - Incidence and prognostic significance of thrombocytopenia developed during acute
      coronary syndrome in contemporary clinical practice.
AB  - BACKGROUND: Prior studies examining thrombocytopenia among patients with acute
      coronary syndromes (ACS) evaluated highly selected patients in a clinical trial
      setting using varying definitions of thrombocytopenia. The incidence, severity,
      and prognostic significance of acquired thrombocytopenia during ACS in community
      practice have not been well defined. METHODS AND RESULTS: We examined 36 182
      patients with non-ST-segment elevation ACS enrolled at 379 US hospitals
      participating in the Can Rapid Risk Stratification of Unstable Angina Patients
      Suppress Adverse Outcomes With Early Implementation of the American College of
      Cardiology/American Heart Association Guidelines (CRUSADE) quality improvement
      initiative between June 2004 and December 2006. Patients with baseline platelet
      counts <150x10(9)/L were excluded. Overall, 4697 patients (13%) developed new
      thrombocytopenia, defined as nadir platelet count <150x10(9)/L (referenced lower
      limit of normal), during their ACS hospitalization. Risks of in-hospital
      mortality and bleeding correlated directly with severity of thrombocytopenia;
      even mild thrombocytopenia (nadir 100 to 149x10(9)/L) was associated with
      increased risks of mortality (adjusted odds ratio [OR], 2.01; 95% CI, 1.69 to
      2.38) and bleeding (adjusted OR, 3.76; 95% CI, 3.43 to 4.12). Each 10% drop in
      platelet count was associated with increased mortality and bleeding risks
      (adjusted ORs, 1.39 [95% CI, 1.33 to 1.46] and 1.89 [95% CI, 1.83 to 1.95],
      respectively). A >/=50% drop in platelet count was associated with higher risk of
      adverse outcomes regardless of the nadir count. A novel combined definition of
      acquired thrombocytopenia-nadir <150x10(9)/L or platelet count drop >or=50%
      identifies a population of ACS patients at higher risk of mortality and major
      bleeding (adjusted ORs, 2.58 [95% CI, 2.23 to 2.98] and 4.32 [95% CI, 3.97 to
      4.70], respectively). CONCLUSIONS: Thrombocytopenia, a common complication of
      ACS, is associated with increased mortality and bleeding risks. Even mild
      thrombocytopenia or a platelet count drop >/=50% in the setting of normal nadir
      values is clinically significant. Application of a combined definition for
      thrombocytopenia using both absolute and relative thresholds permits increased
      sensitivity for patients at high risk of adverse outcomes.

PMID- 19398667
TI  - Differences in specialist consultations for cardiovascular disease by race,
      ethnicity, gender, insurance status, and site of primary care.
AB  - BACKGROUND: Consultation with cardiologists may improve the quality of ambulatory
      care and reduce disparities for patients with heart disease. We assessed the use
      of cardiology consultations and the associated quality by race/ethnicity, gender,
      insurance status, and site of care. METHODS AND RESULTS: In a retrospective
      cohort, we examined electronic records of 9761 adults with coronary artery
      disease or congestive heart failure (CHF) receiving primary care at practices
      affiliated with 2 academic medical centers during 2000 to 2005. During this
      period, 79.6% of patients with coronary artery disease and 90.3% of patients with
      CHF had a cardiology consultation. In multivariate analyses, women were less
      likely to receive a consultation than men for both conditions (coronary artery
      disease: hazard ratio, 0.89; 95% CI, 0.85 to 0.93; CHF: hazard ratio, 0.93; 95%
      CI, 0.87 to 0.99). Women also had 15% fewer follow-up consultations than men
      (P<0.001). Similarly, patients at community health centers were less likely to
      receive a consultation (coronary artery disease: hazard ratio, 0.79; 95% CI, 0.74
      to 0.84; CHF: hazard ratio, 0.77; 95% CI: 0.71 to 0.84) and had 20% fewer follow
      up consultations (P<0.001) relative to those at hospital-based practices. Black
      and Hispanic patients with CHF had 13% fewer follow-up consultations than white
      patients (P=0.01 and P=0.04, respectively). In adjusted analyses, consultation
      was associated with better processes of care compared with no consultation
      (P<0.001), particularly for women (P<0.001 for interaction between consultation
      and gender). CONCLUSIONS: Among ambulatory patients with coronary artery disease
      or CHF, women and those at community health centers have less access to
      cardiologists. Consultation is associated with better quality of care and narrows
      the gender gap in quality.

PMID- 19398668
TI  - Extracellular cardiac matrix biomarkers in patients with acute myocardial
      infarction complicated by left ventricular dysfunction and heart failure:
      insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure
      Efficacy and Survival Study (EPHESUS) study.
AB  - BACKGROUND: Aldosterone stimulates cardiac collagen synthesis. Circulating
      biomarkers of collagen turnover provide a useful tool for the assessment of
      cardiac remodeling in patients with congestive heart failure and left ventricular
      systolic dysfunction after acute myocardial infarction. METHODS AND RESULTS: In a
      substudy of the Eplerenone Post-Acute Myocardial Infarction Heart Failure
      Efficacy and Survival Study (EPHESUS), which evaluated the effects of the
      selective aldosterone receptor antagonist eplerenone versus placebo, serum levels
      of collagen biomarkers were measured in 476 patients with congestive heart
      failure after acute myocardial infarction complicated with left ventricular
      systolic dysfunction. The combination of the type I collagen telopeptide and
      brain natriuretic peptide levels above median at baseline was associated with all
      cause mortality and the composite end point of cardiovascular death or heart
      failure hospitalization, with hazard ratios of 2.49 (P=0.039) and 3.03 (P=0.002),
      respectively. During follow-up, levels of aminoterminal propeptide of type I and
      type III procollagen were found to be consistently lower in the eplerenone group
      and significantly lower beginning at 6 months. CONCLUSIONS: Changes in biomarkers
      of collagen synthesis and degradation suggest that extracellular matrix
      remodeling is an active process in patients with congestive heart failure and
      left ventricular systolic dysfunction after acute myocardial infarction. High
      type I collagen telopeptide and high brain natriuretic peptide serum levels are
      associated with the highest event rate. Eplerenone suppresses post-acute
      myocardial infarction collagen turnover changes.

PMID- 19398669
TI  - MTHFR 677 C>T Polymorphism reveals functional importance for 5
      methyltetrahydrofolate, not homocysteine, in regulation of vascular redox state
      and endothelial function in human atherosclerosis.
AB  - BACKGROUND: The role of circulating homocysteine as an atherosclerosis risk
      factor has recently been questioned. However, 5-methyl-tetrahydrofolate (5-MTHF),
      the circulating metabolite of folic acid participating in homocysteine
      metabolism, has direct effects on vascular function. We sought to distinguish the
      effects of plasma versus vascular tissue 5-MTHF and homocysteine on vascular
      redox and endothelial nitric oxide bioavailability in human vessels. METHODS AND
      RESULTS: We used the methyl tetrahydrofolate reductase (MTHFR) gene polymorphism
      677C>T as a model of chronic exposure of the vascular wall to varying 5-MTHF
      levels in 218 patients undergoing coronary artery bypass graft surgery. Vascular
      superoxide, vascular 5-MTHF, and total homocysteine were determined in saphenous
      veins and internal mammary arteries obtained during surgery. Nitric oxide
      bioavailability was evaluated by organ bath studies on saphenous vein rings.
      MTHFR genotype was a determinant of vascular 5-MTHF (not vascular homocysteine).
      Both MTHFR genotype and vascular 5-MTHF were associated with vascular nitric
      oxide bioavailability and superoxide generated by uncoupled endothelial nitric
      oxide synthase. In contrast, vascular homocysteine was associated only with NADPH
      stimulated superoxide. CONCLUSIONS: Genetic polymorphism 677 C>T on MTHFR affects
      vascular 5-MTHF (but not homocysteine) and can be used as a model to distinguish
      the chronic effects of vascular 5-MTHF from homocysteine on vascular wall.
      Vascular 5-MTHF, rather than plasma or vascular homocysteine, is a key regulator
      of endothelial nitric oxide synthase coupling and nitric oxide bioavailability in
      human vessels, suggesting that plasma homocysteine is an indirect marker of 5
      MTHF rather than a primary regulator of endothelial function.

PMID- 19398670
TI  - Acute kidney injury is associated with increased long-term mortality after
      cardiothoracic surgery.
AB  - BACKGROUND: Long-term survival after acute kidney injury (AKI) is poorly studied.
      We report the relationship between long-term mortality and AKI with small changes
      in serum creatinine during hospitalization after various cardiothoracic surgery
      procedures. METHODS AND RESULTS: This was a retrospective study of 2973 patients
      with no history of chronic kidney disease who were discharged from the hospital
      after cardiothoracic surgery between 1992 and 2002. AKI was defined by the RIFLE
      classification (Risk, Injury, Failure, Loss, and End stage), which requires at
      least a 50% increase in serum creatinine and stratifies patients into 3 grades of
      AKI: Risk, injury, and failure. Patient survival was determined through the
      National Social Security Death Index. Long-term survival was analyzed with a risk
      adjusted Cox proportional hazards regression model. Survival was worse among
      patients with AKI and was proportional to its severity, with an adjusted hazard
      ratio of 1.23 (95% CI 1.06 to 1.42) for the least severe RIFLE risk class and
      2.14 (95% CI 1.73 to 2.66) for the RIFLE failure class compared with patients
      without AKI. Survival was worse among all subgroups of cardiothoracic surgery
      with AKI except for valve surgery. Patients with complete renal recovery after
      AKI still had an increased adjusted hazard ratio for death of 1.28 (95% CI 1.11
      to 1.48) compared with patients without AKI. CONCLUSIONS: The risk of death
      associated with AKI after cardiothoracic surgery remains high for 10 years
      regardless of other risk factors, even for those patients with complete renal
      recovery. Improved renal protection and closer postdischarge follow-up of renal
      function may be warranted.

PMID- 19398671
TI  - Basal and oxidative stress-induced expression of metallothionein is decreased in
      ascending aortic aneurysms of bicuspid aortic valve patients.
AB  - BACKGROUND: Bicuspid aortic valve (BAV) is a heritable condition that has been
      linked by an unknown mechanism to a predisposition for ascending aortic aneurysm.
      Matrix metalloproteinases have been implicated in this predisposition.
      Metallothionein is a poorly characterized, metal-binding protein that regulates
      matrix metalloproteinases and is an antioxidant known to be upregulated under
      oxidative stress. METHODS AND RESULTS: To determine putative factors involved in
      the pathogenesis of aortic aneurysm in BAV patients, our first goal was to
      identify genes that are dysregulated in ascending aortic aneurysms of BAV
      patients compared with tricuspid aortic valve patients and nondiseased (control)
      donors. By microarray analysis (22,000 probe sets), 110 dysregulated genes were
      identified in BAV compared with tricuspid aortic valve patients and control
      donors; 8 were genes of the metallothionein family. Metallothionein gene
      expression and protein expression were significantly lower in aortic tissue and
      cultured aortic smooth muscle cells from BAV patients compared with control
      subjects. Matrix metalloproteinase-9 expression was increased in BAV aortic
      samples relative to controls. BAV aorta was more susceptible to oxidative stress,
      and induction of metallothionein under oxidative stress was reduced in BAV
      patients compared with control subjects. CONCLUSIONS: These results demonstrate
      dysregulated metallothionein expression in ascending aortic smooth muscle cells
      of BAV patients that may contribute to an inadequate response to oxidative stress
      and provoke aneurysm formation. We hypothesize that metallothionein plays a
      pivotal role in the response of ascending aortic smooth muscle cells to oxidative
      stress cues normally involved in the maintenance of the extracellular matrix,
      including the regulation of matrix metalloproteinase expression.

PMID- 19398672
TI  - Images in cardiovascular medicine. Rare case of an unroofed coronary sinus:
      diagnosis by multidetector computed tomography.

PMID- 19398674
TI  - Clopidogrel and the concept of high-risk pharmacokinetics.

PMID- 19398675
TI  - The complex relationship between cholesterol and brain hemorrhage.

PMID- 19398676
TI  - Determinants of aneurysmal aortic disease.

PMID- 19398678
TI  - Evaluation for a ventricular assist device: selecting the appropriate candidate.

PMID- 19398677
TI  - MicroRNAs: regulating a change of heart.

PMID- 19398679
TI  - Images in cardiovascular medicine. Rapid progression of coronary atherosclerosis
      by coronary artery spasm leading to acute coronary syndrome.

PMID- 19398680
TI  - Practice parameter update: management issues for women with epilepsy--focus on
      pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and
      breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and
      Technology Assessment Subcommittee of the American Academy of Neurology and
      American Epilepsy Society.
AB  - OBJECTIVE: To reassess the evidence for management issues related to the care of
      women with epilepsy (WWE) during pregnancy, including preconceptional folic acid
      use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical
      implications of placental and breast milk transfer of antiepileptic drugs (AEDs),
      risks of breastfeeding, and change in AED levels during pregnancy. METHODS: A 20
      member committee evaluated the available evidence based on a structured
      literature review and classification of relevant articles published between 1985
      and October 2007. RESULTS: Preconceptional folic acid supplementation is possibly
      effective in preventing major congenital malformations in the newborns of WWE
      taking AEDs. There is inadequate evidence to determine if the newborns of WWE
      taking AEDs have a substantially increased risk of hemorrhagic complications.
      Primidone and levetiracetam probably transfer into breast milk in amounts that
      may be clinically important. Valproate, phenobarbital, phenytoin, and
      carbamazepine probably are not transferred into breast milk in clinically
      important amounts. Pregnancy probably causes an increase in the clearance and a
      decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent
      carbamazepine, and possibly decreases the level of levetiracetam and the active
      oxcarbazepine metabolite, the monohydroxy derivative. RECOMMENDATIONS:
      Supplementing women with epilepsy with at least 0.4 mg of folic acid before they
      become pregnant may be considered (Level C). Monitoring of lamotrigine,
      carbamazepine, and phenytoin levels during pregnancy should be considered (Level
      B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative)
      levels may be considered (Level C). A paucity of evidence limited the strength of
      many recommendations.

PMID- 19398681
TI  - Practice parameter update: management issues for women with epilepsy--focus on
      pregnancy (an evidence-based review): teratogenesis and perinatal outcomes:
      report of the Quality Standards Subcommittee and Therapeutics and Technology
      Assessment Subcommittee of the American Academy of Neurology and American
      Epilepsy Society.
AB  - OBJECTIVE: To reassess the evidence for management issues related to the care of
      women with epilepsy (WWE) during pregnancy. METHODS: Systematic review of
      relevant articles published between January 1985 and June 2007. RESULTS: It is
      highly probable that intrauterine first-trimester valproate (VPA) exposure has
      higher risk of major congenital malformations (MCMs) compared to carbamazepine
      and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it
      is probable that VPA as part of polytherapy and possible that VPA as monotherapy
      contribute to the development of MCMs. It is probable that antiepileptic drug
      (AED) polytherapy as compared to monotherapy regimens contributes to the
      development of MCMs and to reduced cognitive outcomes. For monotherapy,
      intrauterine exposure to VPA probably reduces cognitive outcomes. Further,
      monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive
      outcomes. Neonates of WWE taking AEDs probably have an increased risk of being
      small for gestational age and possibly have an increased risk of a 1-minute Apgar
      score of <7. RECOMMENDATIONS: If possible, avoidance of valproate (VPA) and
      antiepileptic drug (AED) polytherapy during the first trimester of pregnancy
      should be considered to decrease the risk of major congenital malformations
      (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy
      should be considered to prevent reduced cognitive outcomes (Level B). If
      possible, avoidance of phenytoin and phenobarbital during pregnancy may be
      considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk
      stratification should reflect that the offspring of women with epilepsy taking
      AEDs are probably at increased risk for being small for gestational age (Level B)
      and possibly at increased risk of 1-minute Apgar scores of <7 (Level C).

PMID- 19398683
TI  - The change we need in health care.

PMID- 19398682
TI  - Practice parameter update: management issues for women with epilepsy--focus on
      pregnancy (an evidence-based review): obstetrical complications and change in
      seizure frequency: report of the Quality Standards Subcommittee and Therapeutics
      and Technology Assessment Subcommittee of the American Academy of Neurology and
      American Epilepsy Society.
AB  - OBJECTIVE: To reassess the evidence for management issues related to the care of
      women with epilepsy (WWE) during pregnancy, including the risk of pregnancy
      complications or other medical problems during pregnancy in WWE compared to other
      women, change in seizure frequency, the risk of status epilepticus, and the rate
      of remaining seizure-free during pregnancy. METHODS: A 20-member committee
      including general neurologists, epileptologists, and doctors in pharmacy
      evaluated the available evidence based on a structured literature review and
      classification of relevant articles published between 1985 and February 2008.
      RESULTS: For WWE taking antiepileptic drugs, there is probably no substantially
      increased risk (greater than two times expected) of cesarean delivery or late
      pregnancy bleeding, and probably no moderately increased risk (greater than 1.5
      times expected) of premature contractions or premature labor and delivery. There
      is possibly a substantially increased risk of premature contractions and
      premature labor and delivery during pregnancy for WWE who smoke. Seizure freedom
      for at least 9 months prior to pregnancy is probably associated with a high
      likelihood (84%-92%) of remaining seizure-free during pregnancy. RECOMMENDATIONS:
      Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9
      months prior to pregnancy is probably associated with a high rate (84%-92%) of
      remaining seizure-free during pregnancy (Level B). However, WWE who smoke should
      be counseled that they possibly have a substantially increased risk of premature
      contractions and premature labor and delivery during pregnancy (Level C).

PMID- 19398684
TI  - Cost sharing and the initiation of drug therapy for the chronically ill.
AB  - BACKGROUND: Increased cost sharing reduces utilization of prescription drugs, but
      little evidence demonstrates how this reduction occurs or the factors associated
      with price sensitivity. METHODS: We conducted a retrospective cohort study of
      older adults with employer-provided drug coverage from 1997 to 2002 from 31
      different health plans. We measured the time until initiation of medical therapy
      for 17 183 patients with newly diagnosed hypertension, diabetes, or
      hypercholesterolemia. RESULTS: For all study conditions, higher copayments were
      associated with delayed initiation of therapy. In survival models, doubling
      copayments resulted in large reductions in the predicted proportion of patients
      initiating pharmacotherapy at 1 and 5 years after diagnosis: for hypertension,
      54.8% vs 39.9% at 1 year and 81.6% vs 66.2% at 5 years (P < .001); for
      hypercholesterolemia, 40.2% vs 31.1% at 1 year and 64.3% vs 53.8% at 5 years (P <
      .002); and for diabetes, 45.8% vs 40.0% at 1 year and 69.3% vs 62.9% at 5 years
      (P < .04). However, patients' rate of initiation and sensitivity to copayments
      strongly depended on their prior experience with prescription drugs. Those
      without prior drug use (26.1%, 10.4%, and 12.9%) initiated later (833, >1170, and
      >1402 days later in median time until initiation) and were far more price
      sensitive (increase of 34.5%, 20.1%, and 27.2% remaining untreated after 5 years
      when copayments doubled) than those with a history of drug use among patients
      with newly diagnosed hypertension, hypercholesterolemia, and diabetes,
      respectively. These results were robust to a wide range of sensitivity analyses.
      CONCLUSIONS: High cost sharing delays the initiation of drug therapy for patients
      newly diagnosed with chronic disease. This effect is greater among patients who
      lack experience with prescription drugs. Policy makers and physicians should
      consider the effects of benefits design on patient behavior to encourage the
      adoption of necessary care.

PMID- 19398686
TI  - Prior authorization for antidepressants in Medicaid: effects among disabled dual
      enrollees.
AB  - BACKGROUND: Prior authorization is a popular, but understudied, strategy for
      reducing medication costs. We evaluated the impact of a controversial prior
      authorization policy in Michigan Medicaid on antidepressant use and health
      outcomes among dual Medicaid and Medicare enrollees with a Social Security
      Disability Insurance designation of permanent disability. METHODS: We linked
      Medicaid and Medicare (2000-2003) claims for dual enrollees in Michigan and a
      comparison state, Indiana. Using interrupted time-series and longitudinal data
      analysis, we estimated the impact of the policy on antidepressant medication use,
      treatment initiation, disruptions in therapy, and adverse health events among
      continuously enrolled (Michigan, n = 28 798; Indiana, n = 21 769) and newly
      treated (Michigan, n = 3671; Indiana, n = 2400) patients. RESULTS: In Michigan,
      the proportion of patients starting nonpreferred agents declined from 53%
      prepolicy to 20% postpolicy. The prior authorization policy was associated with a
      small sustained decrease in therapy initiation overall (9 per 10,000 population;
      P = .007). We also observed a short-term increase in switching among established
      users of nonpreferred agents overall (risk ratio, 2.88; 95% confidence interval,
      1.87-4.42) and among those with depression (2.04; 1.22-3.42). However, we found
      no evidence of increased disruptions in treatment or adverse events (ie,
      hospitalization, emergency department use) among newly treated patients.
      CONCLUSIONS: Prior authorization was associated with increased use of preferred
      agents with no evidence of disruptions in therapy or adverse health events among
      new users. However, unintended effects on treatment initiation and switching
      among patients already taking the drug were also observed, lending support to the
      state's previous decision to discontinue prior approval for antidepressants in
      2003.

PMID- 19398687
TI  - Effect of a pharmacist on adverse drug events and medication errors in
      outpatients with cardiovascular disease.
AB  - BACKGROUND: Adverse drug events and medication errors are threats to quality
      care. Inpatient studies suggest that a pharmacist may reduce these events, but
      outpatient studies have not been forthcoming. METHODS: We conducted a pooled
      analysis of 2 randomized controlled trials to determine the effect of pharmacist
      intervention on adverse drug events and medication errors. We studied 800
      outpatient cases of hypertension stratified into complicated (n = 535) and
      uncomplicated (n = 265). Patients in the complicated stratum had heart failure or
      other cardiovascular complication. Computer programs examined 1-year electronic
      record data to identify events classified as adverse drug events and preventable
      or potential adverse drug events. Medication errors included preventable and
      potential adverse drug events. RESULTS: Of the 800 participants (mean [SD] age,
      59 [10] years), 484 (90.5%) and 258 (97.4%) participants remained in the
      complicated and uncomplicated strata, respectively, at 12 months. Compared with
      the control group, the risk of any event was 34% lower in the intervention group
      (risk ratio, 0.66; 95% confidence interval [CI], 0.50-0.88), including a lower
      risk of adverse drug events (risk ratio, 0.65; 95% CI, 0.47-0.90), preventable
      adverse drug events (risk ratio, 0.52; 95% CI, 0.25-1.09), potential adverse drug
      events (risk ratio, 0.70; 95% CI, 0.40-1.22), and medication errors (risk ratio,
      0.63; 95% CI, 0.40-0.98). CONCLUSIONS: This post hoc analysis suggests that
      pharmacist intervention to improve medication use in outpatients with
      cardiovascular disease decreases the risk of adverse drug events and medication
      errors. Further studies are needed to confirm this finding.

PMID- 19398688
TI  - A combined healthy lifestyle score and risk of pancreatic cancer in a large
      cohort study.
AB  - BACKGROUND: Smoking, alcohol use, diet, body mass index (calculated as weight in
      kilograms divided by height in meters squared), and physical activity have been
      studied independently in relation to pancreatic cancer. We generated a healthy
      lifestyle score to investigate their joint effect on risk of pancreatic cancer.
      METHODS: In the prospective National Institutes of Health-AARP Diet and Health
      Study, a total of 450 416 participants aged 50 to 71 years completed the baseline
      food frequency questionnaire (1995-1996) eliciting diet and lifestyle information
      and were followed up through December 31, 2003. We identified 1057 eligible
      incident pancreatic cancer cases. Participants were scored on 5 modifiable
      lifestyle factors as unhealthy (0 points) or healthy (1 point) on the basis of
      current epidemiologic evidence. Participants received 1 point for each respective
      lifestyle factor: nonsmoking, limited alcohol use, adherence to the Mediterranean
      dietary pattern, body mass index (> or =18 and <25), or regular physical
      activity. A combined score (0-5 points) was calculated by summing the scores of
      the 5 factors. Cox proportional hazards regression models were used to estimate
      relative risk (95% confidence interval) for pancreatic cancer. RESULTS: Compared
      with the lowest combined score (0 points), the highest score (5 points) was
      associated with a 58% reduction in risk of developing pancreatic cancer in all
      participants (relative risk, 0.42; 95% confidence interval, 0.26-0.66; P(trend)
      <.001). Scores of less than 5 points were associated with 27% of pancreatic
      cancer cases in our population. CONCLUSION: Findings from this large study
      suggest that having a high score, as opposed to a low score, on an index
      combining 5 modifiable lifestyle factors substantially reduces the risk of
      developing pancreatic cancer.

PMID- 19398689
TI  - Effect of an electronic medication reconciliation application and process
      redesign on potential adverse drug events: a cluster-randomized trial.
AB  - BACKGROUND: Medication reconciliation at transitions in care is a national
      patient safety goal, but its effects on important patient outcomes require
      further evaluation. We sought to measure the impact of an information technology
      based medication reconciliation intervention on medication discrepancies with
      potential for harm (potential adverse drug events [PADEs]). METHODS: We performed
      a controlled trial, randomized by medical team, on general medical inpatient
      units at 2 academic hospitals from May to June 2006. We enrolled 322 patients
      admitted to 14 medical teams, for whom a medication history could be obtained
      before discharge. The intervention was a computerized medication reconciliation
      tool and process redesign involving physicians, nurses, and pharmacists. The main
      outcome was unintentional discrepancies between preadmission medications and
      admission or discharge medications that had potential for harm (PADEs). RESULTS:
      Among 160 control patients, there were 230 PADEs (1.44 per patient), while among
      162 intervention patients there were 170 PADEs (1.05 per patient) (adjusted
      relative risk [ARR], 0.72; 95% confidence interval [CI], 0.52-0.99). A
      significant benefit was found at hospital 1 (ARR, 0.60; 95% CI, 0.38-0.97) but
      not at hospital 2 (ARR, 0.87; 95% CI, 0.57-1.32) (P = .32 for test of effect
      modification). Hospitals differed in the extent of integration of the medication
      reconciliation tool into computerized provider order entry applications at
      discharge. CONCLUSIONS: A computerized medication reconciliation tool and process
      redesign were associated with a decrease in unintentional medication
      discrepancies with potential for patient harm. Software integration issues are
      likely important for successful implementation of computerized medication
      reconciliation tools.

PMID- 19398690
TI  - An electronic health record-based intervention to improve tobacco treatment in
      primary care: a cluster-randomized controlled trial.
AB  - BACKGROUND: To improve the documentation and treatment of tobacco use in primary
      care, we developed and implemented a 3-part electronic health record enhancement:
      (1)smoking status icons, (2) tobacco treatment reminders, and (3) a Tobacco Smart
      Form that facilitated the ordering of medication and fax and e-mail counseling
      referrals. METHODS: We performed a cluster-randomized controlled trial of the
      enhancement in 26 primary care practices between December 19, 2006, and September
      30, 2007. The primary outcome was the proportion of documented smokers who made
      contact with a smoking cessation counselor. Secondary outcomes included coded
      smoking status documentation and medication prescribing. RESULTS: During the 9
      month study period, 132 630 patients made 315 962 visits to study practices.
      Coded documentation of smoking status increased from 37% of patients to 54%
      (+17%) in intervention practices and from 35% of patients to 46% (+11%) in
      control practices (P < .001 for the difference in differences). Among the 9589
      patients who were documented smokers at the start of the study, more patients in
      the intervention practices were recorded as nonsmokers by the end of the study
      (5.3% vs 1.9% in control practices; P < .001). Among 12 207 documented smokers,
      more patients in the intervention practices made contact with a cessation
      counselor (3.9% vs 0.3% in control practices; P < .001). Smokers in the
      intervention practices were no more likely to be prescribed smoking cessation
      medication (2% vs 2% in control practices; P = .40). CONCLUSION: This electronic
      health record-based intervention improved smoking status documentation and
      increased counseling assistance to smokers but not the prescription of cessation
      medication.

PMID- 19398691
TI  - Aspirin plus clopidogrel and risk of infection after coronary artery bypass
      surgery.
AB  - BACKGROUND: The risks associated with the use of the combination of aspirin and
      clopidogrel before surgery are incompletely understood. Pharmacologic suppression
      of platelet function may increase the risk of postoperative infection by
      inhibiting hemostasis, immunity, or both. METHODS: We performed a retrospective
      cohort study of 1677 patients undergoing coronary artery bypass surgery to
      determine the relationship of the preoperative use of aspirin plus clopidogrel vs
      aspirin alone to the 30-day incidence of postoperative surgical site infection
      and bacteremia. RESULTS: The cumulative incidence of infection at 30 days was
      23.1% and 16.1% in patients who were receiving dual antiplatelet therapy and
      aspirin monotherapy, respectively (unadjusted hazard ratio [HR], 1.51; 95%
      confidence interval [CI], 1.09-2.08). The risk of infection remained higher among
      patients who were receiving dual antiplatelet therapy after adjustment for
      demographic, socioeconomic, preoperative, and intraoperative risk factors (HR,
      1.42; 95% CI, 1.01-2.00) and propensity score (HR, 1.43; 95% CI, 1.01-2.01]).
      Transfusion rates were also higher among patients who were receiving dual
      antiplatelet therapy than among patients who were receiving aspirin monotherapy
      (68.4% vs 60.4%, P = .04), but transfusion played a modest role in mediating the
      risk of infection (adjusted HR, 1.37; 95% CI, 0.96-1.93]). Mortality rates at 30
      days were 5.2% and 3.1% in patients who were receiving dual antiplatelet and
      aspirin monotherapy, respectively (adjusted HR, 1.44; 95% CI, 0.70-2.99]).
      CONCLUSIONS: Preoperative use of aspirin plus clopidogrel is associated with an
      increased risk of infection after coronary artery bypass surgery. These findings
      merit additional work to clarify the risks and benefits of uninterrupted dual
      antiplatelet therapy in surgical patients and the impact of platelet inhibition
      on infectious outcomes in populations that are at heightened infectious risk.

PMID- 19398693
TI  - More data needed regarding physician empathy and patient outcome.

PMID- 19398692
TI  - Lifestyle risk factors and new-onset diabetes mellitus in older adults: the
      cardiovascular health study.
AB  - BACKGROUND: The combined impact of lifestyle factors on incidence of diabetes
      mellitus later in life is not well established. The objective of this study was
      to determine how lifestyle factors, assessed in combination, relate to new-onset
      diabetes in a broad and relatively unselected population of older adults.
      METHODS: We prospectively examined associations of lifestyle factors, measured
      using repeated assessments later in life, with incident diabetes mellitus during
      a 10-year period (1989-1998) among 4883 men and women 65 years or older (mean
      [SD] age at baseline, 73 [6] years) enrolled in the Cardiovascular Health Study.
      Low-risk lifestyle groups were defined by physical activity level (leisure-time
      activity and walking pace) above the median; dietary score (higher fiber intake
      and polyunsaturated to saturated fat ratio, lower trans-fat intake and lower mean
      glycemic index) in the top 2 quintiles; never smoked or former smoker more than
      20 years ago or for fewer than 5 pack-years; alcohol use (predominantly light or
      moderate); body mass index less than 25 (calculated as weight in kilograms
      divided by height in meters squared); and waist circumference of 88 cm for women
      or 92 cm for men. The main outcome measure was incident diabetes defined annually
      by new use of insulin or oral hypoglycemic medications. We also evaluated fasting
      and 2-hour postchallenge glucose levels. RESULTS: During 34,539 person-years, 337
      new cases of drug-treated diabetes mellitus occurred (9.8 per 1000 person-years).
      After adjustment for age, sex, race, educational level, and annual income, each
      lifestyle factor was independently associated with incident diabetes. Overall,
      the rate of incident diabetes was 35% lower (relative risk, 0.65; 95% confidence
      interval, 0.59-0.71) for each 1 additional lifestyle factor in the low-risk
      group. Participants whose physical activity level and dietary, smoking, and
      alcohol habits were all in the low-risk group had an 82% lower incidence of
      diabetes (relative risk, 0.18; 95% confidence interval, 0.06-0.56) compared with
      all other participants. When absence of adiposity (either body mass index <25 or
      waist circumference < or =88/92 cm for women/men) was added to the other 4 low
      risk lifestyle factors, incidence of diabetes was 89% lower (relative risk, 0.11;
      95% confidence interval, 0.01-0.76). Overall, 9 of 10 new cases of diabetes
      appeared to be attributable to these 5 lifestyle factors. Associations were
      slightly attenuated, but still highly significant, for incident diabetes defined
      by medication use or glucose level. CONCLUSION: Even later in life, combined
      lifestyle factors are associated with a markedly lower incidence of new-onset
      diabetes mellitus.

PMID- 19398694
TI  - Hospital admissions related to medications and implementing guidelines.

PMID- 19398695
TI  - Adverse events related to medications leading to hospitalization.

PMID- 19398696
TI  - Risk factors for community-acquired infections caused by extended-spectrum beta
      lactamase-producing Escherichia coli.

PMID- 19398697
TI  - Regarding consequences of inadequate sign-out for patient care.

PMID- 19398698
TI  - Teaching NeuroImages: focal ischemia of the spinal micturition center and
      detrusor-external sphincter dyssynergia.

PMID- 19398699
TI  - Teaching NeuroImages: "Penguin" or "hummingbird" sign and midbrain atrophy in
      progressive supranuclear palsy.

PMID- 19398700
TI  - Using botulinum toxin to treat diabetic foot pain.

PMID- 19398702
TI  - Changes in MRS neuronal markers and T cell phenotypes observed during early HIV
      infection.
AB  - OBJECTIVE: To determine if changes in brain metabolites are observed during early
      HIV infection and correlate these changes with immunologic alterations. METHODS:
      Eight subjects with early HIV infection, 9 HIV-seronegative controls, and 10
      chronically HIV-infected subjects without neurologic impairment underwent 1H
      magnetic resonance spectroscopy. Subjects with early stage infection were
      identified near the time of HIV seroconversion and imaged within 60 days of an
      evolving Western blot, while still having detectable plasma virus. Subjects had
      blood drawn for viral RNA and T cell quantification. RESULTS: Both N
      acetylaspartate (NAA) and Glx (glutamate + glutamine) were decreased in the
      frontal cortical gray matter of seropositive subjects. NAA levels were found to
      be decreased in the centrum semiovale white matter of chronically HIV-infected
      subjects, but not in those with early infection. Both HIV-infected cohorts
      demonstrated a lower number of CD4+ T lymphocytes and a higher number of CD8+ T
      lymphocytes in their blood. Lower NAA levels in the frontal cortex of subjects
      with early infection were associated with an expansion of CD8+ T cells,
      especially effector CD8+ T cells. CONCLUSIONS: These results verify metabolism
      changes occurring in the brain early during HIV infection. Lower NAA and Glx
      levels in the cortical gray matter suggests that HIV causes neuronal dysfunction
      soon after infection, which correlates to the expansion of CD8+ T cells,
      specifically to an activated phenotype. Utilizing magnetic resonance spectroscopy
      to track NAA levels may provide important information on brain metabolic health
      while allowing better understanding of the virus-host interactions involved in
      CNS functional deficits.

PMID- 19398703
TI  - Quantification of sweat gland innervation: a clinical-pathologic correlation.
AB  - OBJECTIVE: To evaluate a novel method to quantify the density of nerve fibers
      innervating sweat glands in healthy control and diabetic subjects, to compare the
      results to an unbiased stereologic technique, and to identify the relationship to
      standardized physical examination and patient-reported symptom scores. METHODS:
      Thirty diabetic and 64 healthy subjects had skin biopsies performed at the distal
      leg and distal and proximal thigh. Nerve fibers innervating sweat glands, stained
      with PGP 9.5, were imaged by light microscopy. Sweat gland nerve fiber density
      (SGNFD) was quantified by manual morphometry. As a gold standard, three
      additional subjects had biopsies analyzed by confocal microscopy using unbiased
      stereologic quantification. Severity of neuropathy was measured by standardized
      instruments including the Neuropathy Impairment Score in the Lower Limb (NIS-LL)
      while symptoms were measured by the Michigan Neuropathy Screening Instrument.
      RESULTS: Manual morphometry increased with unbiased stereology (r = 0.93, p <
      0.01). Diabetic subjects had reduced SGNFD compared to controls at the distal leg
      (p < 0.001), distal thigh (p < 0.01), and proximal thigh (p < 0.05). The SGNFD at
      the distal leg of diabetic subjects decreased as the NIS-LL worsened (r = -0.89,
      p < 0.001) and was concordant with symptoms of reduced sweat production (p <
      0.01). CONCLUSIONS: We describe a novel method to quantify the density of nerve
      fibers innervating sweat glands. The technique differentiates groups of patients
      with mild diabetic neuropathy from healthy control subjects and correlates with
      both physical examination scores and symptoms relevant to sudomotor dysfunction.
      This method provides a reliable structural measure of sweat gland innervation
      that complements the investigation of small fiber neuropathies.

PMID- 19398705
TI  - In vivo mapping of amyloid toxicity in Alzheimer disease.
AB  - OBJECTIVE: To study the relationship between gray matter atrophy and amyloid
      deposition in Alzheimer disease (AD). METHODS: Volumetric magnetic resonance (MR)
      and [11C]-PIB PET were acquired from 23 patients with AD and 17 healthy older
      persons. Standardized [11C]-PIB uptake values were coregistered to MR scans in a
      standard space. Decreased density of and increased [11C]-PIB uptake in the gray
      matter of patients with AD vs controls were assessed with both voxel-based (p <
      0.05 corrected) and region-of-interest (ROI) analyses. The relationship between
      decreased density of and increased [11C]-PIB uptake in the gray matter was
      investigated with voxel-based Pearson r maps (thresholded at p < 0.05) and ROI
      linear regression plots. RESULTS: Atrophy mapped to the hippocampus and increased
      [11C]-PIB uptake to large frontal, parietal, and posterior cingulate cortical
      areas. ROI analysis showed the largest effect size for atrophy in the hippocampus
      (2.01) and amygdala (1.27) and the highest effect size for [11C]-PIB uptake in
      frontal (2.66), posterior cingulate/retrosplenial (2.43), insular (2.41), and
      temporal (2.23) regions. In the hippocampus, [11C]-PIB uptake was significantly
      increased, but effect size was milder (1.72). Significant correlations between
      atrophy and increased [11C]-PIB uptake were found in the hippocampal (r = -0.54)
      and amygdalar ROIs (r = -0.40) but not in the frontal, temporal, posterior
      cingulate/retrosplenial, insular, and caudate ROIs (r between 0.04 and 0.25).
      CONCLUSION: The medial temporal lobe might be highly susceptible to amyloid
      toxicity, whereas neocortical areas might be more resilient.

PMID- 19398704
TI  - Neuropathologic intermediate phenotypes enhance association to Alzheimer
      susceptibility alleles.
AB  - OBJECTIVE: The identification of susceptibility alleles to risk of Alzheimer
      disease (AD) is a major public health priority. Using apolipoprotein E genotype
      (APOE), we examined whether neuropathologic intermediate phenotypes, the
      pathology underlying clinical AD that presumably lies intermediate in the causal
      chain, would increase power for genetic associations. METHODS: More than 700
      older persons underwent annual evaluation and organ donation as part of the
      Religious Orders Study or Rush Memory and Aging Project. A total of 536 autopsied
      persons with clinical AD or without dementia with APOE genotyping and a
      quantitative measure of AD pathology were analyzed. Regression analyses were used
      to examine the relation of APOE to clinical AD, to the level of cognitive
      function proximate to death, and to measures of AD neuropathology. RESULTS: APOE
      epsilon4 was associated with increased odds of clinical AD (p = 3 x 10(-7)), and
      its association with level of cognition was stronger (p = 8 x 10(-12)). However,
      the use of quantitative measures of AD pathology markedly enhanced the
      association (p = 9 x 10(-24)). The APOE epsilon2 was not associated with either
      AD (p = 0.69) or level of cognition (p = 0.82). However, its association with AD
      pathology (p = 1 x 10(-5)) was sufficiently strong that it would have warranted
      follow-up if discovered in a genome-wide association study. Power calculations
      demonstrate that a sample size of 625 subjects with our measure of AD pathology
      would be required to meet genome-wide significance of p = 5 x 10(-8) for
      epsilon2. CONCLUSION: Discovery efforts for susceptibility loci for Alzheimer
      disease could benefit from the use of neuropathologic intermediate phenotypes as
      a complement to other approaches.

PMID- 19398706
TI  - Near-infrared spectroscopy in carotid artery stenting predicts cerebral
      hyperperfusion syndrome.
AB  - OBJECTIVE: Cerebral hyperperfusion syndrome (CHS) following carotid artery
      stenting (CAS) or carotid endarterectomy (CEA) is rare but often fatal once
      intracranial hemorrhage has occurred. In particular, CHS occurs significantly
      earlier after CAS than after CEA. Thus a monitoring method for early detection of
      CHS is required. Near-infrared spectroscopy (NIRS) provides a noninvasive
      monitoring technique for assessing regional cerebral oxygen saturation (rSO2).
      This study evaluated the usefulness of transcranial NIRS during CAS for
      prediction of CHS. METHODS: Periprocedural rSO2 was monitored in 64 cases of CAS
      (52 men, 12 women; 71 +/- 6.6 years). The average degree of carotid stenosis was
      76.8 +/- 11.3% by North American Symptomatic Carotid Endarterectomy Trial
      criteria. Bifrontal rSO2 was monitored during the procedure using NIRS. Seventeen
      patients were symptomatic and 47 were asymptomatic. CHS was diagnosed by
      increased cerebral blood flow by SPECT performed on the day after treatment with
      deterioration of neurologic symptoms. RESULTS: CHS was observed in two cases
      (3.1%). In the CHS group, post-reperfusion rSO2 values increased >24% from
      baseline until 3 minutes after reperfusion. In the non-CHS group, the normal
      upper limit (NUL) of the rSO2 change was set at 10.0% at 3 minutes after
      reperfusion. In the CHS group, rSO2 at 3 minutes after reperfusion was markedly
      higher than the NUL. In patients showing an rSO2 at 3 minutes after reperfusion
      increased by more than 10.0%, CHS following CAS could be predicted. CONCLUSION:
      Periprocedural increases in regional cerebral oxygen saturation measured by near-
      infrared spectroscopy can be an excellent predictor of cerebral hyperperfusion
      syndrome after carotid artery stenting.

PMID- 19398707
TI  - Risk of dementia in MCI: combined effect of cerebrovascular disease, volumetric
      MRI, and 1H MRS.
AB  - OBJECTIVE: To investigate the combined ability of hippocampal volumes, 1H
      magnetic resonance spectroscopy (MRS) metabolites, and cerebrovascular disease to
      predict the risk of progression to dementia in mild cognitive impairment (MCI).
      METHODS: We identified 151 consecutively recruited subjects with MCI from the
      Mayo Clinic Alzheimer's Disease Research Center and Patient Registry who
      underwent MRI and 1H MRS studies at baseline and were followed up with
      approximately annual clinical examinations. A multivariable proportional hazards
      model that considered all imaging predictors simultaneously was used to determine
      whether hippocampal volumes, posterior cingulate gyrus 1H MRS metabolites, white
      matter hyperintensity load, and presence of cortical and subcortical infarctions
      are complementary in predicting the risk of progression from MCI to dementia.
      RESULTS: Seventy-five subjects with MCI progressed to dementia by last follow-up.
      The model that best predicted progression to dementia included age, sex,
      hippocampal volumes, N-acetylaspartate (NAA)/creatine (Cr) on 1H MRS, and
      cortical infarctions. Based on age- and sex-adjusted Kaplan-Meier plots, we
      estimated that by 3 years, 26% of the MCI patients with normal hippocampal
      volumes, NAA/Cr ratios >1 SD, and no cortical infarctions will progress to
      dementia, compared with 78% of the MCI patients with hippocampal atrophy, low
      NAA/Cr (< or =1 SD), and cortical infarction. CONCLUSIONS: Multiple magnetic
      resonance (MR) markers of underlying dementia pathologies improve the ability to
      identify patients with prodromal dementia over a single MR marker, supporting the
      concept that individuals with multiple brain pathologies have increased odds of
      dementia compared with individuals with a single pathology.

PMID- 19398708
TI  - Altered anandamide degradation in attention-deficit/hyperactivity disorder.

PMID- 19398709
TI  - Abnormal eye movements in Kennedy disease.

PMID- 19398710
TI  - Nail in the midbrain.

PMID- 19398711
TI  - Phenomenology of prolonged febrile seizures: results of the FEBSTAT study.

PMID- 19398712
TI  - Phenomenology of prolonged febrile seizures: results of the FEBSTAT study.

PMID- 19398713
TI  - Qualitative analysis of the role of culture in coping themes of Latina and
      European American mothers of children with cancer.
AB  - It has been well established that mothers of children diagnosed with cancer
      experience high levels of distress. Latina mothers may be at risk for higher
      levels of distress related to language barriers, cultural factors, and economic,
      immigration, and acculturation stressors. Despite the increasing US Latino
      population, few studies have examined the role of culture within pediatric
      oncology, including how mothers cope with their child's cancer. This study used
      qualitative analysis of 24 sessions from 3 Latina and 3 European American mothers
      of children recently diagnosed with cancer. The session transcripts were divided
      into a total of 2328 thought segments that were then analyzed for themes using a
      collaborative iterative process. Analysis identified 9 shared coping themes that
      included, with some variations: gathering information, professional help-seeking,
      activities, problem solving, positive thinking, present orientation, reframing,
      avoidance, and religion. Three themes were culture specific: only European
      American mothers discussed compromise, whereas normalization and perspective
      taking were unique to the Latina mothers and suggest that the cultural value of
      simpatia influences coping. Clinical and research recommendations are discussed.

PMID- 19398714
TI  - Diagnostic dilemma: solitary fibrous tumor or hemangiopericytoma of the
      submandibular region in a patient with multiple odontogenic keratocysts.
AB  - Solitary fibrous tumors (SFTs) are rare spindle cell neoplasms that originate
      from mesothelial-lined surfaces, mainly the pleura and peritoneum. SFT is a
      distinctive mesenchymal neoplasm of the pleura but can be found in extrapleural
      sites. The treatment of SFT is simple excision or wide local resection. This is
      the case study of a 14-year-old girl who presented with a large diffuse swelling
      in the left submandibular region, ultimately diagnosed with SFT and surgically
      excised.

PMID- 19398715
TI  - Behavioral inhibition and its relation to anxiety and depression symptoms in
      adolescents with sickle cell disease: a preliminary study.
AB  - Several investigations have found support for the role of behavioral inhibition
      in the etiology of childhood anxiety and depression disorders. However, nothing
      is known about how this relation extends to children with a chronic, life
      threatening illness. The purpose of the current study was to examine behavioral
      inhibition and its relation to anxiety and depression symptoms among 30
      adolescents with sickle cell disease (SCD). Adolescents with SCD and their
      primary caregivers completed instruments assessing demographic information,
      behavioral inhibition, and anxiety and depression symptoms. A majority of
      adolescents with SCD classified themselves as middle or low on behavioral
      inhibition. Adolescents with SCD who classified themselves as high on behavioral
      inhibition displayed higher levels of anxiety and depression than adolescents
      with SCD who classified themselves as low on behavioral inhibition; adolescents
      with SCD endorsing the middle behavioral inhibition category generally scored in
      between. These data extend previous work with healthy children and adolescents
      and suggest that early and continued assessment of behavioral inhibition may be
      important in preventing adverse psychological outcomes among a group that is
      already at risk for internalizing disorders.

PMID- 19398716
TI  - Phase 1 multicenter dose-escalation study of ezatiostat hydrochloride (TLK199
      tablets), a novel glutathione analog prodrug, in patients with myelodysplastic
      syndrome.
AB  - Phase 1 testing of ezatiostat, a glutathione S-transferase P1-1 inhibitor, for
      the treatment of myelodysplastic syndrome was conducted in a multidose-escalation
      study. Patients received 10 dose levels (200, 400, 1000, 1400, 2000, 2400, 3000,
      4000, 5000, and 6000 mg) of ezatiostat tablets in divided doses on days 1 to 7 of
      a 21-day cycle for a maximum of 8 cycles. The safety and pharmacokinetics of
      ezatiostat were evaluated. Forty-five patients with low to intermediate-2
      International Prognostic Scoring System risk myelodysplastic syndrome were
      enrolled. No dose-limiting toxicities were observed. The most common grade 1 or
      2, respectively, treatment-related adverse events were nonhematologic: nausea
      (56%, 9%), diarrhea (36%, 7%), vomiting (24%, 7%), abdominal pain (9%, 0%),
      constipation (4%, 9%), anorexia (3%, 7%), and dyspepsia (3%, 7%). Concentration
      of the primary active metabolite, TLK236, increased proportionate to ezatiostat
      dosage. Seventeen hematologic improvement (HI) responses by International Working
      Group criteria were observed at dose levels of 200 to 6000 mg/day with 11 HI
      responses at doses of 4000 to 6000 mg/day. HI responses occurred in all lineages
      including 3 bilineage and 1 complete cytogenetic response. Decreased number of
      red blood cell and platelet transfusions and in some cases transfusion
      independence were attained. Extended dose schedules of ezatiostat tablets are
      under investigation.

PMID- 19398717
TI  - MSCs inhibit monocyte-derived DC maturation and function by selectively
      interfering with the generation of immature DCs: central role of MSC-derived
      prostaglandin E2.
AB  - Various studies analyzed the inhibitory effect exerted by mesenchymal stem cells
      (MSCs) on cells of the innate or acquired immunity. Myeloid dendritic cells (DCs)
      are also susceptible to such inhibition. In this study, we show that MSCs
      strongly inhibit DC generation from peripheral blood monocytes. In the presence
      of MSCs, monocytes supplemented with granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and interleukin-4 (IL-4) did not acquire the surface phenotype
      typical of immature (CD14(-), CD1a(+)) or mature (CD80(+), CD86(+), CD83(+)) DCs,
      failed to produce IL-12, and did not induce T-cell activation or proliferation.
      Analysis of the molecular mechanism(s) responsible for the inhibitory effect
      revealed a major role of prostaglandin E(2) (PGE(2)). Thus, addition of the
      PGE(2) inhibitor NS-398 restored DC differentiation and function. Moreover,
      PGE(2) directly added to cultures of monocytes blocked their differentiation
      toward DCs in a manner similar to MSCs. Although IL-6 has been proposed to play a
      role in MSC-mediated inhibition of DC differentiation, our data indicate that
      PGE(2) and not IL-6 represents the key inhibitory mediator. Indeed, NS-398
      inhibited PGE(2) production and restored DC differentiation with no effect on IL
      6 production. These data emphasize the role of MSCs in inhibiting early DC
      maturation and identifying the molecular mechanisms responsible for the
      inhibitory effect.

PMID- 19398718
TI  - Peripheral mural cell recruitment requires cell-autonomous heparan sulfate.
AB  - Blood vessel maturation and stability require recruitment of mural cells (MCs) to
      the nascent vessel. Loss or detachment of MCs causes vascular dysfunction in
      diseases. N-sulfation of heparan sulfate (HS) is required for platelet-derived
      growth factor B (PDGF-B) retention and platelet-derived growth factor receptor
      beta (PDGFR-beta) signaling during MC recruitment. To analyze the specific role
      of MC-derived HS in this process, we inactivated HS synthesis in MCs. MC-specific
      loss of HS causes embryonic lethality associated with vascular patterning
      defects, edema, and hemorrhages during late gestation. MC recruitment in the skin
      is impaired, correlating with defective PDGFR-beta and transforming growth factor
      beta (TGF-beta)-SMAD signaling. Accumulation of rounded cells positive for MC
      markers close to the vessels indicates defective polarization and migration of
      local MC progenitors. In contrast, MC recruitment and signaling in the central
      nervous system (CNS) are unaffected by MC HS loss. Our results suggest that HS is
      selectively required in a cell-autonomous manner, acting in cis with PDGFR-beta
      and TGF-beta receptors during induction/polarization and migration of local
      progenitor cells to the nascent vessel. Once MCs are in contact with the vessel,
      as during CNS vascularization, endothelial HS appears sufficient to facilitate
      PDGFR-beta activation in trans.

PMID- 19398719
TI  - Molecular stratification model for prognosis in cytogenetically normal acute
      myeloid leukemia.
AB  - We have evaluated 9 new molecular markers (ERG, EVI1, MLL-PTD, MN1, PRAME, RHAMM,
      and WT1 gene-expression levels plus FLT3 and NPM1 mutations) in 121 de novo
      cytogenetically normal acute myeloblastic leukemias. In the multivariate
      analysis, high ERG or EVI1 and low PRAME expressions were associated with a
      shorter relapse-free survival (RFS) and overall survival (OS). A 0 to 3 score was
      given by assigning a value of 0 to favorable parameters (low ERG, low EVI1, and
      high PRAME) and 1 to adverse parameters. This model distinguished 4 subsets of
      patients with different OS (2-year OS of 79%, 65%, 46%, and 27%; P = .001) and
      RFS (2-year RFS of 92%, 65%, 49%, and 43%; P = .005). Furthermore, this score
      identified patients with different OS (P = .001) and RFS (P = .013), even within
      the FLT3/NPM1 intermediate-risk/high-risk subgroups. Here we propose a new
      molecular score for cytogenetically normal acute myeloblastic leukemias, which
      could improve patient risk-stratification.

PMID- 19398720
TI  - Participation of the urokinase receptor in neutrophil efferocytosis.
AB  - The urokinase receptor (uPAR) plays an important role in regulation of
      fibronolysis, cell migration, and adhesion. In this study, we examined whether
      uPAR plays a role in modulating efferocytosis of neutrophils. Macrophages from
      uPAR(-/-) mice demonstrated enhanced ability to engulf viable wild-type (WT)
      neutrophils in vitro and in vivo in the lungs. The increased phagocytic activity
      of uPAR(-/-) macrophages was abrogated by incubation with soluble uPAR (suPAR),
      arginine-glycine-aspartic acid (RGD)-containing peptides, or anti-integrin
      antibodies. There was increased uptake of viable uPAR(-/-) neutrophils by WT
      macrophages. Incubation of uPAR(-/-) neutrophils with suPAR or anti-integrin
      antibodies diminished uptake by WT macrophages to baseline. Uptake of uPAR(-/-)
      neutrophils by uPAR(-/-) macrophages was not enhanced. However, incubation of
      uPAR(-/-) neutrophils or uPAR(-/-) macrophages, but not both, with suPAR enhanced
      the uptake of viable uPAR(-/-) neutrophils by uPAR(-/-) macrophages. The adhesion
      of WT neutrophils to uPAR(-/-) macrophages was higher than to WT macrophages.
      uPAR(-/-) neutrophils demonstrated increased adhesion to suPAR, which was
      abrogated by blocking of low-density lipoprotein related protein and integrins.
      Expression of uPAR on the surface of apoptotic neutrophils was reduced compared
      with levels on viable neutrophils. These results demonstrate a novel role for
      uPAR in modulating recognition and clearance of neutrophils.

PMID- 19398722
TI  - Understanding the safety net: inpatient quality of care varies based on how one
      defines safety-net hospitals.
AB  - A challenge to investigating quality of care at safety-net hospitals is the
      absence of a standard method for identifying these hospitals. The authors
      identified three different, commonly used approaches for classifying hospitals as
      safety-net providers. Analyzing national data on hospital demographics and
      quality of care, they found little overlap among these three sets of hospitals.
      Under two definitions, safety-net providers clearly underperformed on quality
      compared with non-safety-net providers; under a third definition, results were
      mixed. How one defines safety-net providers can affect health services research
      outcomes and policy recommendations.

PMID- 19398721
TI  - MicroRNA profiling identifies miR-34a and miR-21 and their target genes JAG1 and
      WNT1 in the coordinate regulation of dendritic cell differentiation.
AB  - MicroRNAs (miRNAs, miRs) modulate a multitude of cellular events. Here, we
      identify functional miRNA-protein networks that regulate human monocyte-derived
      dendritic cell (MDDC) differentiation. miRNA profiling revealed stage-specific
      differential expression of 20 miRNAs during days 1, 3, and 5 of MDDC
      differentiation. To identify and prioritize miRNA-protein networks for functional
      validation, we developed a target ranking algorithm that incorporates many
      features of miRNA regulatory networks. This system prioritized miR-21, miR-34a,
      and their cognate targets WNT1 and JAG1 for functional validation. Inhibition of
      both miR-21 and miR-34a stalled MDDC differentiation, as quantified by DC
      SIGN/CD14 expression ratios, showing cooperative involvement of these miRNAs in
      MDDC differentiation. We confirmed that the 3' untranslated regions of WNT1 and
      JAG1 were functional targets of these miRNAs and provide evidence that these
      targets were translationally suppressed. Significantly, exogenously added Wnt-1
      and Jagged-1 also stalled MDDC differentiation, suggesting that miRNA-mediated
      inhibition of endogenous WNT1 and JAG1 expression was important for proper MDDC
      differentiation. Finally, inhibition of miR-21 and miR-34a, or addition of Wnt-1
      and Jagged-1, led to a decrease in endocytic capacity, a key function of immature
      DCs. Thus, our novel approach identified and validated some miRNA-protein
      networks involved in phenotypic and functional MDDC differentiation.

PMID- 19398725
TI  - High-profile death throws spotlight on error reports.

PMID- 19398726
TI  - Radiologists virtually unwrap mummy's secrets.

PMID- 19398727
TI  - Canada lags US in adoption of e-prescribing.

PMID- 19398728
TI  - The routine of death.

PMID- 19398730
TI  - An open letter to the minister of health.

PMID- 19398731
TI  - Cardiovascular risk and glycemic control.

PMID- 19398732
TI  - Can anticoagulation care be improved with technology?

PMID- 19398733
TI  - Personalized medicine: a transformative approach is needed.

PMID- 19398735
TI  - Tainted weight-loss products.

PMID- 19398737
TI  - Residents claim 24-hour call violates Charter rights.

PMID- 19398738
TI  - Effect of interactions between C peptide levels and insulin treatment on clinical
      outcomes among patients with type 2 diabetes mellitus.
AB  - BACKGROUND: A recently halted clinical trial showed that intensive treatment of
      type 2 diabetes mellitus was associated with increased mortality. Given the
      phenotypic heterogeneity of diabetes, therapy targeted at insulin status may
      maximize benefits and minimize harm. METHODS: In this longitudinal cohort study,
      we followed 503 patients with type 2 diabetes who were free of cardiovascular
      disease from 1996 until data on mortality and cardiovascular outcomes were
      censored in 2005. Phenotype-targeted therapy was defined as use of insulin
      therapy in patients with a fasting plasma C peptide level of 0.2 nmol/L or less
      and no insulin therapy in patients with higher C peptide levels. RESULTS: The
      mean age of the cohort was 54.4 (standard deviation 13.1) years, and 56% were
      women. The mean duration of diabetes was 4.6 years (range 0-35.9 years). Of the
      503 patients, 110 (21.9%) had a low C peptide level and 111 (22.1%) were given
      insulin. Based on their C peptide status, 338 patients (67.2%) received phenotype
      targeted therapy (non-insulin-treated, high C peptide level [n = 310] or insulin
      treated, low C peptide level [n = 28]), and 165 patients (32.8%) received non
      phenotype-targeted therapy (non-insulin-treated, low C peptide level [n = 82] or
      insulin-treated, high C peptide level [n = 83]). Compared with the insulin
      treated, low-C-peptide referent group, the insulin-treated, high-C-peptide group
      was at a significantly higher risk of cardiovascular events (hazard ratio [HR]
      2.85, p = 0.049) and death (HR 3.43, p = 0.043); the risk was not significantly
      higher in the other 2 groups. These differences were no longer significant after
      adjusting for age, sex and diabetes duration. INTERPRETATION: Patients with low C
      peptide levels who received insulin had the best clinical outcomes. Patients with
      normal to high C peptide levels who received insulin had the worst clinical
      outcomes. The results suggest that phenotype-targeted insulin therapy may be
      important in treating diabetes.

PMID- 19398739
TI  - Effect of an interactive voice response system on oral anticoagulant management.
AB  - BACKGROUND: Monitoring oral anticoagulants is logistically challenging for both
      patients and medical staff. We evaluated the effect of adding an interactive
      voice response system to computerized decision support for oral anticoagulant
      management. METHODS: We developed an interactive voice response system to
      communicate to patients the results of international normalized ratio testing and
      their dosage schedules for anticoagulation therapy. The system also reminded
      patients of upcoming and missed appointments for blood tests. We recruited
      patients whose anticoagulation control was stable after at least 3 months of
      warfarin therapy. We prospectively examined clinical data and outcomes for these
      patients for an intervention period of at least 3 months. We also collected
      retrospective data for each patient for the 3 months before study enrolment.
      RESULTS: We recruited 226 patients between Nov. 23, 2006, and Aug. 1, 2007. The
      mean duration of the intervention period (prospective data collection) was 4.2
      months. Anticoagulation control was similar for the periods during and preceding
      the intervention (mean time within the therapeutic range 80.3%, 95% confidence
      interval [CI] 77.5% to 83.1% v. 79.9%, 95% CI 77.3% to 82.6%). The interactive
      voice response system delivered 1211 (77.8%) of 1557 scheduled dosage messages,
      with no further input required from clinic staff. The most common reason for
      clinic staff having to deliver the remaining messages (accounting for 143 [9.2%]
      of all messages) was an international normalized ratio that was excessively high
      or low, (i.e., 0.5 or more outside the therapeutic range). When given the option,
      76.6% of patients (164/214) chose to continue with the interactive voice response
      system for management of their anticoagulation after the study was completed. The
      system reduced staff workload for monitoring anticoagulation therapy by 48
      min/wk, a 33% reduction from the baseline of 2.4 hours. INTERPRETATION:
      Interactive voice response systems have a potential role in improving the
      monitoring of patients taking oral anticoagulants. Further work is required to
      determine the generalizability and cost-effectiveness of these results.

PMID- 19398741
TI  - Managing evidence-based knowledge: the need for reliable, relevant and readable
      resources.

PMID- 19398740
TI  - Medication errors in critical care: risk factors, prevention and disclosure.

PMID- 19398742
TI  - The toddler with 1 striped leg: a linear papular rash.

PMID- 19398743
TI  - Pancreas divisum: a cause of idiopathic acute pancreatitis.

PMID- 19398744
TI  - Diastolic heart failure.

PMID- 19398745
TI  - A picture of global health.

PMID- 19398749
TI  - Tension gastrothorax: a life-threatening cause of acute abdominal pain.

PMID- 19398750
TI  - Scrubs: what you don't see is what you get.

PMID- 19398753
TI  - A challenge to Goliath.
AB  - Megapublishers obligate librarians to buy hundreds of journals they do not need
      in order to access the journals their constituents actually read. The time has
      come to challenge this business model, which is unsustainable for the libraries.

PMID- 19398754
TI  - Myeloid heme oxygenase-1 regulates innate immunity and autoimmunity by modulating
      IFN-beta production.
AB  - Heme oxygenase-1 (HO-1) is a key cytoprotective, antioxidant, and
      antiinflammatory molecule. The pathophysiological functions of HO-1 have been
      associated with its enzymatic activities in heme catabolism. We have examined the
      immune functions of HO-1 by its conditional ablation in myeloid cells (HO-1(M-KO)
      mice). We demonstrate that myeloid HO-1 is required for the activation of
      interferon (IFN) regulatory factor (IRF) 3 after Toll-like receptor 3 or 4
      stimulation, or viral infection. HO-1-deficient macrophages show reduced
      expression of IFN-beta and of primary IRF3 target genes encoding RANTES, IP-10
      and MCP-1. In the presence of polyI:C, myeloid HO-1 knockout mice infected with
      Listeria monocytogenes, a model dependent on IFN-beta production, showed enhanced
      bacterial clearance and survival, whereas control mice succumbed to infection.
      Moreover, after induction of experimental autoimmune encephalomyelitis, mice with
      myeloid-specific HO-1 deficiency developed a higher incidence and an exacerbated,
      nonremitting clinical disease correlating with persistent activation of antigen
      presenting cells, enhanced infiltration of Th17 cells, and a nonregressing myelin
      specific T cell reactivity. Notably, these defects were rectified by exogenous
      administration of IFN-beta, confirming that HO-1 functions directly upstream of
      this critical immune pathway. These results uncover a novel direct function for
      myeloid HO-1 in the regulation of IFN-beta production, establishing HO-1 as a
      critical early mediator of the innate immune response.

PMID- 19398755
TI  - M-CSF inhibition selectively targets pathological angiogenesis and
      lymphangiogenesis.
AB  - Antiangiogenic therapy for the treatment of cancer and other neovascular diseases
      is desired to be selective for pathological angiogenesis and lymphangiogenesis.
      Macrophage colony-stimulating factor (M-CSF), a cytokine required for the
      differentiation of monocyte lineage cells, promotes the formation of high-density
      vessel networks in tumors and therefore possesses therapeutic potential as an M
      CSF inhibitor. However, the physiological role of M-CSF in vascular and lymphatic
      development, as well as the precise mechanisms underlying the antiangiogenic
      effects of M-CSF inhibition, remains unclear. Moreover, therapeutic potential of
      M-CSF inhibition in other neovascular diseases has not yet been evaluated. We
      used osteopetrotic (op/op) mice to demonstrate that M-CSF deficiency reduces the
      abundance of LYVE-1(+) and LYVE1(-) macrophages, resulting in defects in vascular
      and lymphatic development. In ischemic retinopathy, M-CSF was required for
      pathological neovascularization but was not required for the recovery of normal
      vasculature. In mouse osteosarcoma, M-CSF inhibition effectively suppressed tumor
      angiogenesis and lymphangiogenesis, and it disorganized extracellular matrices.
      In contrast to VEGF blockade, interruption of M-CSF inhibition did not promote
      rapid vascular regrowth. Continuous M-CSF inhibition did not affect healthy
      vascular and lymphatic systems outside tumors. These results suggest that M-CSF
      targeted therapy is an ideal strategy for treating ocular neovascular diseases
      and cancer.

PMID- 19398756
TI  - A challenge to Goliath.
AB  - Megapublishers obligate librarians to buy hundreds of journals they do not need
      in order to access the journals their constituents actually read. The time has
      come to challenge this business model, which is unsustainable for the libraries.

PMID- 19398758
TI  - The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T
      cells.
AB  - The interaction between a T cell and an antigen-presenting cell (APC) can trigger
      a signaling response that leads to T cell activation. Prior studies have shown
      that ligation of the T cell receptor (TCR) triggers a signaling cascade that
      proceeds through the coalescence of TCR and various signaling molecules (e.g.,
      the kinase Lck and adaptor protein LAT [linker for T cell activation]) into
      microdomains on the plasma membrane. In this study, we investigated another
      ligand-receptor interaction (CD58-CD2) that facilities T cell activation using a
      model system consisting of Jurkat T cells interacting with a planar lipid bilayer
      that mimics an APC. We show that the binding of CD58 to CD2, in the absence of
      TCR activation, also induces signaling through the actin-dependent coalescence of
      signaling molecules (including TCR-zeta chain, Lck, and LAT) into microdomains.
      When simultaneously activated, TCR and CD2 initially colocalize in small
      microdomains but then partition into separate zones; this spatial segregation may
      enable the two receptors to enhance signaling synergistically. Our results show
      that two structurally distinct receptors both induce a rapid spatial
      reorganization of molecules in the plasma membrane, suggesting a model for how
      local increases in the concentration of signaling molecules can trigger T cell
      signaling.

PMID- 19398759
TI  - Active establishment of centromeric CENP-A chromatin by RSF complex.
AB  - Centromeres are chromosomal structures required for equal DNA segregation to
      daughter cells, comprising specialized nucleosomes containing centromere protein
      A (CENP-A) histone, which provide the basis for centromeric chromatin assembly.
      Discovery of centromere protein components is progressing, but knowledge related
      to their establishment and maintenance remains limited. Previously, using anti
      CENP-A native chromatin immunoprecipitation, we isolated the interphase
      centromere complex (ICEN). Among ICEN components, subunits of the remodeling and
      spacing factor (RSF) complex, Rsf-1 and SNF2h proteins, were found. This paper
      describes the relationship of the RSF complex to centromere structure and
      function, demonstrating its requirement for maintenance of CENP-A at the
      centromeric core chromatin in HeLa cells. The RSF complex interacted with CENP-A
      chromatin in mid-G1. Rsf-1 depletion induced loss of centromeric CENP-A, and
      purified RSF complex reconstituted and spaced CENP-A nucleosomes in vitro. From
      these data, we propose the RSF complex as a new factor actively supporting the
      assembly of CENP-A chromatin.

PMID- 19398760
TI  - Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae.
AB  - We studied the function of the cyclin-dependent kinase Cdc28 (Cdk1) in the DNA
      damage response and maintenance of genome stability using Saccharomyces
      cerevisiae. Reduced Cdc28 activity sensitizes cells to chronic DNA damage, but
      Cdc28 is not required for cell viability upon acute exposure to DNA-damaging
      agents. Cdc28 is also not required for activation of the DNA damage and
      replication checkpoints. Chemical-genetic analysis reveals that CDC28 functions
      in an extensive network of pathways involved in maintenance of genome stability,
      including homologous recombination, sister chromatid cohesion, the spindle
      checkpoint, postreplication repair, and telomere maintenance. In addition, Cdc28
      and Mre11 appear to cooperate to prevent mitotic catastrophe after DNA
      replication arrest. We show that reduced Cdc28 activity results in suppression of
      gross chromosomal rearrangements (GCRs), indicating that Cdc28 is required for
      formation or recovery of GCRs. Thus, we conclude that Cdc28 functions in a
      genetic network that supports cell viability during DNA damage while promoting
      the formation of GCRs.

PMID- 19398761
TI  - FOXC2 controls formation and maturation of lymphatic collecting vessels through
      cooperation with NFATc1.
AB  - The mechanisms of blood vessel maturation into distinct parts of the blood
      vasculature such as arteries, veins, and capillaries have been the subject of
      intense investigation over recent years. In contrast, our knowledge of lymphatic
      vessel maturation is still fragmentary. In this study, we provide a molecular and
      morphological characterization of the major steps in the maturation of the
      primary lymphatic capillary plexus into collecting lymphatic vessels during
      development and show that forkhead transcription factor Foxc2 controls this
      process. We further identify transcription factor NFATc1 as a novel regulator of
      lymphatic development and describe a previously unsuspected link between NFATc1
      and Foxc2 in the regulation of lymphatic maturation. We also provide a genome
      wide map of FOXC2-binding sites in lymphatic endothelial cells, identify a novel
      consensus FOXC2 sequence, and show that NFATc1 physically interacts with FOXC2
      binding enhancers. As damage to collecting vessels is a major cause of lymphatic
      dysfunction in humans, our results suggest that FOXC2 and NFATc1 are potential
      targets for therapeutic intervention.

PMID- 19398762
TI  - Lattices, rafts, and scaffolds: domain regulation of receptor signaling at the
      plasma membrane.
AB  - The plasma membrane is organized into various subdomains of clustered
      macromolecules. Such domains include adhesive structures (cellular synapses,
      substrate adhesions, and cell-cell junctions) and membrane invaginations
      (clathrin-coated pits and caveolae), as well as less well-defined domains such as
      lipid rafts and lectin-glycoprotein lattices. Domains are organized by
      specialized scaffold proteins including the intramembranous caveolins, which
      stabilize lipid raft domains, and the galectins, a family of animal lectins that
      cross-link glycoproteins forming molecular lattices. We review evidence that
      these heterogeneous microdomains interact to regulate substratum adhesion and
      cytokine receptor dynamics at the cell surface.

PMID- 19398763
TI  - K63-linked ubiquitin chains as a specific signal for protein sorting into the
      multivesicular body pathway.
AB  - A growing number of yeast and mammalian plasma membrane proteins are reported to
      be modified with K63-linked ubiquitin (Ub) chains. However, the relative
      importance of this modification versus monoubiquitylation in endocytosis, Golgi
      to endosome traffic, and sorting into the multivesicular body (MVB) pathway
      remains unclear. In this study, we show that K63-linked ubiquitylation of the
      Gap1 permease is essential for its entry into the MVB pathway. Carboxypeptidase S
      also requires modification with a K63-Ub chain for correct MVB sorting. In
      contrast, monoubiquitylation of a single target lysine of Gap1 is a sufficient
      signal for its internalization from the cell surface, and Golgi to endosome
      transport of the permease requires neither its ubiquitylation nor the Ub-binding
      GAT (Gga and Tom1) domain of Gga (Golgi localizing, gamma-ear containing, ARF
      binding) adapter proteins, the latter being crucial for subsequent MVB sorting of
      the permease. Our data reveal that K63-linked Ub chains act as a specific signal
      for MVB sorting, providing further insight into the Ub code of membrane protein
      trafficking.

PMID- 19398765
TI  - Advances in interventional neuroradiology.
AB  - In 2008 we witnessed a rapid advancement in stent technology, which is reflected
      in the high number of case reports, publications of case series, and randomized
      trials. Stents not only served for a combined intrasaccular and extrasaccular
      treatment of challenging aneurysms but also assisted the revascularization in
      acute and chronic ischemic conditions of the neurovascular system. Although a
      self-expanding nitinol semiopen cell stent is currently used for intracranial
      occlusive disease, a new retrievable closed-cell designed stent is widely used
      for aneurysms because of its easy delivery through a microcatheter in frequently
      tortuous head and neck as well as cerebrovascular circulation (Figure 1).
      However, despite numerous publications in the field, the widespread acceptance of
      the use of stents to routinely treat carotid stenosis awaits the results of the
      multicenter randomized clinical trials that should be available in 2009. The role
      of interventional neuroradiology in the treatment of acute ischemic stroke
      continues to expand and excite interest.

PMID- 19398766
TI  - The experiences of adolescents and adults conceived by sperm donation:
      comparisons by age of disclosure and family type.
AB  - BACKGROUND: This study presents findings from a large sample of donor offspring
      who are aware of the nature of their conception. Importantly, this is one of the
      first studies to compare the views of offspring told of their origins during
      childhood to those who found out during adulthood. METHODS: Online questionnaires
      were completed anonymously by donor offspring who were members of the Donor
      Sibling Registry, a US-based worldwide registry that helps donor-conceived
      individuals search for and contact their donor and donor siblings (i.e. half
      siblings). Data were obtained on offspring's feelings about being donor conceived
      and their feelings towards their parents. RESULTS: Offspring of single mothers
      and lesbian couples learnt of their donor origins earlier than offspring of
      heterosexual couples. Those told later in life reported more negative feelings
      regarding their donor conception than those told earlier. Offspring's feelings
      towards their parents were less clear, with some of those told later reporting
      more positive feelings and others reporting more negative feelings. Offspring
      from heterosexual-couple families were more likely to feel angry at being lied to
      by their mothers than by their fathers. The most common feeling towards fathers
      was 'sympathetic'. CONCLUSIONS: Age of disclosure is important in determining
      donor offspring's feelings about their donor conception. It appears it is less
      detrimental for children to be told about their donor conception at an early age.

PMID- 19398767
TI  - Transcriptome changes in renal allograft protocol biopsies at 3 months precede
      the onset of interstitial fibrosis/tubular atrophy (IF/TA) at 6 months.
AB  - BACKGROUND: Interstitial fibrosis and tubular atrophy (IF/TA) in renal
      transplants are the major morphological correlates of progressive graft
      deterioration. Early diagnosis of IF/TA is a pre-requisite for a timely
      therapeutic intervention in patients at risk. To evaluate events occurring before
      the overt onset of IF/TA, gene expression profiling of 3-month protocol biopsies
      from patients with IF/TA was performed in a patient group (n = 8) who developed
      mild IF/TA [chronic allograft nephropathy (CAN) grade I, by the Banff scoring
      system] in the subsequent 6-month protocol biopsy ('progressors'), and in 12
      patients without IF/TA at 6 months ('non-progressors'). METHODS: RNA was
      extracted, labelled and hybridized to human specific genome wide DNA microarrays.
      Normalized data were subjected to gene-centric and pathway-centric statistical
      methods. RESULTS: Compared to the non-progressors, the 3-month biopsies of the
      progressor group showed overexpression of several genes that are important in the
      T- and B-cell activation and immune response. Genes involved in pro-fibrotic
      processes were identified in the biopsies of the progressors that preceded the
      observed IF/TA at 6 months. Furthermore, several genes with transporter and
      metabolic functions were underrepresented in the progressors in the 3-month
      biopsies. CONCLUSION: Gene expression profiling of early protocol biopsies
      identified changes in the transcriptome of grafts, which may be important for the
      development of IF/TA. Such early detection of transcriptome changes can
      facilitate the identification of patients at risk shifting the intervention time
      point well before the histological diagnosis of irreversible IF/TA.

PMID- 19398768
TI  - Evidence that msh1p plays multiple roles in mitochondrial base excision repair.
AB  - Mitochondrial DNA is thought to be especially prone to oxidative damage by
      reactive oxygen species generated through electron transport during cellular
      respiration. This damage is mitigated primarily by the base excision repair (BER)
      pathway, one of the few DNA repair pathways with confirmed activity on
      mitochondrial DNA. Through genetic epistasis analysis of the yeast Saccharomyces
      cerevisiae, we examined the genetic interaction between each of the BER proteins
      previously shown to localize to the mitochondria. In addition, we describe a
      series of genetic interactions between BER components and the MutS homolog MSH1,
      a respiration-essential gene. We show that, in addition to their variable effects
      on mitochondrial function, mutant msh1 alleles conferring partial function
      interact genetically at different points in mitochondrial BER. In addition to
      this separation of function, we also found that the role of Msh1p in BER is
      unlikely to be involved in the avoidance of large-scale deletions and
      rearrangements.

PMID- 19398769
TI  - Large-scale functional annotation and expanded implementations of the P{wHy}
      hybrid transposon in the Drosophila melanogaster genome.
AB  - Whole genome sequencing of the model organisms has created increased demand for
      efficient tools to facilitate the genome annotation efforts. Accordingly, we
      report the further implementations and analyses stemming from our publicly
      available P{wHy} library for Drosophila melanogaster. A two-step regime-large
      scale transposon mutagenesis followed by hobo-induced nested deletions-allows
      mutation saturation and provides significant enhancements to existing genomic
      coverage. We previously showed that, for a given starting insert, deletion
      saturation is readily obtained over a 60-kb interval; here, we perform a
      breakdown analysis of efficiency to identify rate-limiting steps in the process.
      Transrecombination, the hobo-induced recombination between two P{wHy} half
      molecules, was shown to further expand the P{wHy} mutational range, pointing to a
      potent, iterative process of transrecombination-reconstitution-transrecombination
      for alternating between very large and very fine-grained deletions in a self
      contained manner. A number of strains also showed partial or complete repression
      of P{wHy} markers, depending on chromosome location, whereby asymmetric marker
      silencing allowed continuous phenotypic detection, indicating that P{wHy}-based
      saturational mutagenesis should be useful for the study of
      heterochromatin/positional effects.

PMID- 19398771
TI  - Mutation in bovine beta-carotene oxygenase 2 affects milk color.
AB  - beta-Carotene biochemistry is a fundamental process in mammalian biology.
      Aberrations either through malnutrition or potentially through genetic variation
      may lead to vitamin A deficiency, which is a substantial public health burden. In
      addition, understanding the genetic regulation of this process may enable bovine
      improvement. While many bovine QTL have been reported, few of the causative genes
      and mutations have been identified. We discovered a QTL for milk beta-carotene
      and subsequently identified a premature stop codon in bovine beta-carotene
      oxygenase 2 (BCO2), which also affects serum beta-carotene content. The BCO2
      enzyme is thereby identified as a key regulator of beta-carotene metabolism.

PMID- 19398772
TI  - Cell-to-cell transport through plasmodesmata in tree callus cultures.
AB  - One factor that contributes to a successful fruit tree grafting is the
      establishment of symplasmic contacts in the graft interface to facilitate the
      transfer of compounds between scion and stock. Using novel experimental and
      theoretical approaches we investigated whether the localized incompatibility,
      experienced in some Prunus grafts, could be related to insufficient plasmodesmal
      coupling at an early stage of development within one of the partners. Dye
      coupling analysis using fluorescent tracers combined with confocal laser scanning
      microscopy were performed in cultured callus from either the plum rootstock
      (Prunus cerasifera Ehrh. x Prunus munsoniana W. Wight et Hedr.) cv. 'Marianna
      2624' or from the apricot (Prunus armeniaca L.) cv. 'Moniqui' growing in vitro.
      Fluorescein was loaded into callus cells in a caged form. Following
      photoactivation of fluorescence within single cells, the uncaged fluorescein
      could be traced as it was spreading cell-to-cell revealing the existence of
      functional plasmodesmata. This set of experiments was performed within the
      'stock' partner in callus fusions ('callus grafts') as well as in ungrafted
      callus. The results indicated species-related as well as developmental-related
      differences in plasmodesmal conductivity. The results further pointed to a novel
      control factor of connectivity that reaches the graft partner and changes its
      innate rate of communication: when combining the poorly transporting apricot
      cultivar with the well-transporting plum cultivar, communication between plum
      callus cells was much reduced, compared to that in plum homografts. For further
      support of the hypothesis, we carried out a quantitative analysis in which
      fluorescein was esterloaded into the callus. Fluorescence redistribution after
      photobleaching of fluorescein in individual cells gave a measure for the
      plasmodesmal contact between the cells. We found significant differences between
      the species with regard to mobile fraction and halftime of redistribution, which
      confirmed that callus cells are not interconnected to the same extent in Marianna
      2624 and Moniqui.

PMID- 19398770
TI  - Snf1 controls the activity of adr1 through dephosphorylation of Ser230.
AB  - The transcription factors Adr1 and Cat8 act in concert to regulate the expression
      of numerous yeast genes after the diauxic shift. Their activities are regulated
      by Snf1, the yeast homolog of the AMP-activated protein kinase of higher
      eukaryotes. Cat8 is regulated directly by Snf1, but how Snf1 regulates Adr1 is
      unknown. Mutations in Adr1 that alleviate glucose repression are clustered
      between amino acids 227 and 239. This region contains a consensus sequence for
      protein kinase A, RRAS(230)F, and Ser230 is phosphorylated in vitro by both
      protein kinase A and Ca(++) calmodulin-dependent protein kinase. Using an
      antiphosphopeptide antibody, we found that the level of Adr1 phosphorylated on
      Ser230 was highest in glucose-grown cells and decreased in a Snf1-dependent
      manner when glucose was depleted. A nonphosphorylatable Ser230Ala mutant was no
      longer Snf1 dependent for activation of Adr1-dependent genes and could suppress
      Cat8 dependence at genes coregulated by Adr1 and Cat8. Contrary to expectation,
      neither protein kinase A (PKA) nor Ca(++) calmodulin-dependent protein kinase
      appeared to have an important role in Ser230 phosphorylation in vivo, and a
      screen of 102 viable kinase deletion strains failed to identify a candidate
      kinase. We conclude that either Ser230 is phosphorylated by multiple protein
      kinases or its kinase is encoded by an essential gene. Using the Ser230Ala
      mutant, we explain a long-standing observation of synergy between Adr1
      constitutive mutants and Snf1 activation and conclude that dephosphorylation of
      Ser230 via a Snf1-dependent pathway appears to be a major component of Adr1
      regulation.

PMID- 19398774
TI  - Uncooperative voltage sensors.

PMID- 19398775
TI  - A single charged voltage sensor is capable of gating the Shaker K+ channel.
AB  - We sought to determine the contribution of an individual voltage sensor to
      Shaker's function. Concatenated heterotetramers of Shaker zH4 Delta(6-46) wild
      type (wt) in combination with a neutral S4 segment Shaker mutant (mut) with
      stoichiometries 2wt/2mut and 1wt/3mut were studied and compared with the 4wt
      concatenated homotetramer. A single charged voltage sensor is sufficient to open
      Shaker conductance with reduced delay (<1 ms) and at more hyperpolarized voltages
      compared with 4wt. In addition, the wt-like slow inactivation of 1wt/3mut was
      almost completely eliminated by mutations T449V-I470C in its single wt subunit,
      indicating that the subunits bearing a neutral S4 were unable to trigger slow
      inactivation. Our results strongly suggest that a neutral S4 segment of Shaker's
      subunit is voltage insensitive and its voltage sensor is in the activated
      position (i.e., ready for pore opening), and provide experimental support to the
      proposed model of independent voltage sensors with a final, almost voltage
      independent concerted step.

PMID- 19398776
TI  - Ionic selectivity in L-type calcium channels by electrostatics and hard-core
      repulsion.
AB  - A physical model of selective "ion binding" in the L-type calcium channel is
      constructed, and consequences of the model are compared with experimental data.
      This reduced model treats only ions and the carboxylate oxygens of the EEEE locus
      explicitly and restricts interactions to hard-core repulsion and ion-ion and ion
      dielectric electrostatic forces. The structural atoms provide a flexible
      environment for passing cations, thus resulting in a self-organized induced-fit
      model of the selectivity filter. Experimental conditions involving binary
      mixtures of alkali and/or alkaline earth metal ions are computed using
      equilibrium Monte Carlo simulations in the grand canonical ensemble. The model
      pore rejects alkali metal ions in the presence of biological concentrations of
      Ca(2+) and predicts the blockade of alkali metal ion currents by micromolar
      Ca(2+). Conductance patterns observed in varied mixtures containing Na(+) and
      Li(+), or Ba(2+) and Ca(2+), are predicted. Ca(2+) is substantially more potent
      in blocking Na(+) current than Ba(2+). In apparent contrast to experiments using
      buffered Ca(2+) solutions, the predicted potency of Ca(2+) in blocking alkali
      metal ion currents depends on the species and concentration of the alkali metal
      ion, as is expected if these ions compete with Ca(2+) for the pore. These
      experiments depend on the problematic estimation of Ca(2+) activity in solutions
      buffered for Ca(2+) and pH in a varying background of bulk salt. Simulations of
      Ca(2+) distribution with the model pore bathed in solutions containing a varied
      amount of Li(+) reveal a "barrier and well" pattern. The entry/exit barrier for
      Ca(2+) is strongly modulated by the Li(+) concentration of the bath, suggesting a
      physical explanation for observed kinetic phenomena. Our simulations show that
      the selectivity of L-type calcium channels can arise from an interplay of
      electrostatic and hard-core repulsion forces among ions and a few crucial channel
      atoms. The reduced system selects for the cation that delivers the largest charge
      in the smallest ion volume.

PMID- 19398779
TI  - A challenge to Goliath.
AB  - Megapublishers obligate librarians to buy hundreds of journals they do not need
      in order to access the journals their constituents actually read. The time has
      come to challenge this business model, which is unsustainable for the libraries.

PMID- 19398777
TI  - DHPR activation underlies SR Ca2+ release induced by osmotic stress in isolated
      rat skeletal muscle fibers.
AB  - Changes in skeletal muscle volume induce localized sarcoplasmic reticulum (SR)
      Ca(2+) release (LCR) events, which are sustained for many minutes, suggesting a
      possible signaling role in plasticity or pathology. However, the mechanism by
      which cell volume influences SR Ca(2+) release is uncertain. In the present
      study, rat flexor digitorum brevis fibers were superfused with isoosmotic
      Tyrode's solution before exposure to either hyperosmotic (404 mOsm) or
      hypoosmotic (254 mOsm) solutions, and the effects on cell volume, membrane
      potential (E(m)), and intracellular Ca(2+) ([Ca(2+)](i)) were determined. To
      allow comparison with previous studies, solutions were made hyperosmotic by the
      addition of sugars or divalent cations, or they were made hypoosmotic by reducing
      [NaCl](o). All hyperosmotic solutions induced a sustained decrease in cell
      volume, which was accompanied by membrane depolarization (by 14-18 mV; n = 40)
      and SR Ca(2+) release. However, sugar solutions caused a global increase in
      [Ca(2+)](i), whereas solutions made hyperosmotic by the addition of divalent
      cations only induced LCR. Decreasing osmolarity induced an increase in cell
      volume and a negative shift in E(m) (by 15.04 +/- 1.85 mV; n = 8), whereas
      [Ca(2+)](i) was unaffected. However, on return to the isoosmotic solution,
      restoration of cell volume and E(m) was associated with LCR. Both global and
      localized SR Ca(2+) release were abolished by the dihydropyridine receptor
      inhibitor nifedipine by sustained depolarization of the sarcolemmal or by the
      addition of the ryanodine receptor 1 inhibitor tetracaine. Inhibitors of the Na-K
      2Cl (NKCC) cotransporter markedly inhibited the depolarization associated with
      hyperosmotic shrinkage and the associated SR Ca(2+) release. These findings
      suggest (1) that the depolarization that accompanies a decrease in cell volume is
      the primary event leading to SR Ca(2+) release, and (2) that volume-dependent
      regulation of the NKCC cotransporter contributes to the observed changes in E(m).
      The differing effects of the osmotic agents can be explained by the screening of
      fixed charges by divalent ions.

PMID- 19398780
TI  - Review of recent advances in spectrum imaging and its extension to reciprocal
      space.
AB  - Using examples from various domains of science, this review covers some recent
      developments in spectrum imaging (SI) using scanning transmission electron
      microscopy (STEM) and electron energy loss spectroscopy (EELS). Advanced multi
      dimensional acquisition methods allow the acquisition of STEM-EELS data with
      other complementary data such as energy dispersive X-ray spectroscopy (EDS),
      cathodoluminescence and even combining them with reciprocal space analysis
      through a new method called diffraction imaging. This method allows real and
      reciprocal space information to be mixed to get a more complete description of
      the electron-sample interaction. The developments in SI data analysis such as
      multiple linear least-squares fitting, non-linear least-squares fitting and
      multivariate analysis allow for a robust extraction not only of each elemental
      distribution but also of each chemical phase in a sample through an intuitive
      computer-assisted method.

PMID- 19398778
TI  - Intracellular calcium strongly potentiates agonist-activated TRPC5 channels.
AB  - TRPC5 is a calcium (Ca(2+))-permeable nonselective cation channel expressed in
      several brain regions, including the hippocampus, cerebellum, and amygdala.
      Although TRPC5 is activated by receptors coupled to phospholipase C, the precise
      signaling pathway and modulatory signals remain poorly defined. We find that
      during continuous agonist activation, heterologously expressed TRPC5 currents are
      potentiated in a voltage-dependent manner ( approximately 5-fold at positive
      potentials and approximately 25-fold at negative potentials). The reversal
      potential, doubly rectifying current-voltage relation, and permeability to large
      cations such as N-methyl-d-glucamine remain unchanged during this potentiation.
      The TRPC5 current potentiation depends on extracellular Ca(2+): replacement by
      Ba(2+) or Mg(2+) abolishes it, whereas the addition of 10 mM Ca(2+) accelerates
      it. The site of action for Ca(2+) is intracellular, as simultaneous fura-2
      imaging and patch clamp recordings indicate that potentiation is triggered at
      approximately 1 microM [Ca(2+)]. This potentiation is prevented when
      intracellular Ca(2+) is tightly buffered, but it is promoted when recording with
      internal solutions containing elevated [Ca(2+)]. In cell-attached and excised
      inside-out single-channel recordings, increases in internal [Ca(2+)] led to an
      approximately 10-20-fold increase in channel open probability, whereas single
      channel conductance was unchanged. Ca(2+)-dependent potentiation should result in
      TRPC5 channel activation preferentially during periods of repetitive firing or
      coincident neurotransmitter receptor activation.

PMID- 19398781
TI  - First application of Cc-corrected imaging for high-resolution and energy-filtered
      TEM.
AB  - Contrast-transfer calculations indicate that C(c) correction should be highly
      beneficial for high-resolution and energy-filtered transmission electron
      microscopy. A prototype of an electron optical system capable of correcting
      spherical and chromatic aberration has been used to verify these calculations. A
      strong improvement in resolution at an acceleration voltage of 80 kV has been
      measured. Our first C(c)-corrected energy-filtered experiments examining a
      (LaAlO(3))(0.3)(Sr(2)AlTaO(6))(0.7)/LaCoO(3) interface demonstrated a significant
      gain for the spatial resolution in elemental maps of La.

PMID- 19398783
TI  - Thromboembolic prophylaxis for total knee arthroplasty in Asian patients: a
      randomised controlled trial.
AB  - PURPOSE: To compare the efficacy and safety of different modes of thromboembolic
      prophylaxis for elective total knee arthroplasty (TKA) in Asian patients.
      METHODS: 440 low-risk patients undergoing TKA were randomised into 4 equal
      groups: (1) no prophylaxis (control), (2) graduated compression stockings (GCS),
      (3) intermittent pneumatic compression (IPC), and (4) low-molecular-weight
      heparin (enoxaparin). Duplex ultrasonography was used as an assessment tool.
      RESULTS: The deep vein thrombosis point prevalence was highest in the control
      group (22%), which was significantly higher than in patients receiving IPC (8%,
      p=0.032) or enoxaparin (6%, p=0.001). One patient each in the control and GCS
      groups developed a non-fatal pulmonary embolism. Patients on enoxaparin received
      more blood transfusions and 2 of them had major bleeding complications.
      CONCLUSION: IPC is the preferred method of thromboprophylaxis for TKA in Asian
      patients.

PMID- 19398782
TI  - Heparan sulfate proteoglycans are receptors for the cell-surface trafficking and
      biological activity of transglutaminase-2.
AB  - Transglutaminase type 2 (TG2) is both a protein cross-linking enzyme and a cell
      adhesion molecule with an elusive unconventional secretion pathway. In normal
      conditions, TG2-mediated modification of the extracellular matrix modulates cell
      motility, proliferation and tissue repair, but under continuous cell insult,
      higher expression and elevated extracellular trafficking of TG2 contribute to the
      pathogenesis of tissue scarring. In search of TG2 ligands that could contribute
      to its regulation, we characterized the affinity of TG2 for heparan sulfate (HS)
      and heparin, an analogue of the chains of HS proteoglycans (HSPGs). By using
      heparin/HS solid-binding assays and surface plasmon resonance we showed that
      purified TG2 has high affinity for heparin/HS, comparable to that for
      fibronectin, and that cell-surface TG2 interacts with heparin/HS. We demonstrated
      that cell-surface TG2 directly associates with the HS chains of syndecan-4
      without the mediation of fibronectin, which has affinity for both syndecan-4 and
      TG2. Functional inhibition of the cell-surface HS chains of wild-type and
      syndecan-4-null fibroblasts revealed that the extracellular cross-linking
      activity of TG2 depends on the HS of HSPG and that syndecan-4 plays a major but
      not exclusive role. We found that heparin binding did not alter TG2 activity per
      se. Conversely, fibroblasts deprived of syndecan-4 were unable to effectively
      externalize TG2, resulting in its cytosolic accumulation. We propose that the
      membrane trafficking of TG2, and hence its extracellular activity, is linked to
      TG2 binding to cell-surface HSPG.

PMID- 19398784
TI  - Heparin versus danaproid for prevention of venous thromboembolism after hip
      surgery.
AB  - PURPOSE: To compare the prevalence of deep vein thrombosis (DVT), pulmonary
      thromboembolism (PTE), and bleeding complications in patients receiving heparin
      or danaproid after hemiarthroplasty or osteosynthesis for hip fractures. METHODS:
      37 men and 138 women aged 47 to 100 (mean, 80) years underwent either
      hemiarthroplasty or osteosynthesis for hip fractures; 5 patients with dementia
      were excluded. All patients received preoperative elastic stocking and
      postoperative intermittent pneumatic compression. They were divided into 3 groups
      based on their admission period: controls (n=71), unfractionated heparin (n=44),
      and danaproid sodium (n=55). Drugs were administered from postoperative day 1 to
      7. At day 7, all patients undertook radioisotope venography of the legs and lung
      perfusion scintigraphy. RESULTS: In the control, heparin, and danaproid groups
      respectively, the DVT rates were 31%, 9.1%, and 5.5%, and the PTE rates were
      5.6%, 4.5%, and 1.8%. Only the DVT rate in the control group was significantly
      higher than that in the heparin and danaproid groups. In the heparin group, one
      patient had gastrointestinal bleeding, 5 developed wound haematomas, and one had
      leakage from the drain site for 2 weeks. CONCLUSION: Danaproid sodium appeared
      more effective and safer than heparin, with no bleeding complications occurred.

PMID- 19398785
TI  - Philos plate fixation for proximal humeral fractures.
AB  - PURPOSE: To evaluate the efficacy of Philos plate fixation for proximal humerus
      fractures. METHODS: Functional outcomes of 31 men and 27 women aged 36 to 73
      (mean, 61) years who underwent Philos plate fixation for proximal humeral
      fractures were retrospectively reviewed. Indications for surgery were 3-part
      (n=33) or 4-part (n=25) closed proximal humeral fractures with angulation of more
      than 45 degrees or displacement of more than 1 cm. Functional outcomes and
      shoulder range of movement were assessed based on the Constant scoring system.
      RESULTS: Patients were followed up for 12 to 18 (mean, 15) months. All fractures
      healed satisfactorily, except in one patient with a valgus 4-part fracture who
      had malunion. No wound infections, vascular injuries, avascular necrosis, or loss
      of fixation ensued. Two patients with axillary nerve palsy recovered
      spontaneously within 3 months. Functional outcome was excellent in 13 patients,
      good in 36, moderate in 8, and poor in 1. The mean Constant score was 80 (range,
      40-100). CONCLUSION: The Philos plate fixation is appropriate treatment for
      proximal humeral fractures.

PMID- 19398786
TI  - Philos plate fixation for displaced proximal humeral fractures.
AB  - PURPOSE: To evaluate the treatment outcome of Philos plate fixation for displaced
      proximal humeral fractures in 27 consecutive patients. METHODS: 6 men and 21
      women aged 22 to 85 (mean, 56) years underwent Philos plate fixation for
      displaced proximal humeral fractures. 11 patients were aged 60 years or younger
      and 16 older than 60 years. All fractures were closed with no associated injuries
      and classified as 2-part (n=13), 3-part (n=12), and 4-part (n=2), according to
      the Neer classification. Patients were assessed radiologically and functionally
      using the Constant shoulder score. RESULTS: Patients were followed up for 6 to 24
      (mean, 13) months. All the fractures united except in a 76- year-old woman with a
      3-part fracture in whom there was fracture collapse and screw penetration of the
      humeral head at 6 weeks. She subsequently developed non-union and avascular
      necrosis. The mean Constant shoulder score was 70 (range, 28-88). 11 patients had
      a score exceeding 75, 13 were scored between 50 and 75, and 3 were below 50.
      CONCLUSION: Philos plate fixation provided stable fixation, minimal metal work
      problems and enabled early range-of-motion exercises to achieve acceptable
      functional results.

PMID- 19398787
TI  - Diluted povidone-iodine versus saline for dressing metal-skin interfaces in
      external fixation.
AB  - PURPOSE: To compare infection rates associated with 2 dressing solutions for
      metal-skin interfaces. METHODS: 60 patients who underwent distraction
      osteogenesis with external fixators were equally randomised into 2 dressing
      solution groups (diluted povidone-iodine vs. saline). Fixations were attained
      using either rigid stainless steel 5-mm diameter half pins or smooth stainless
      steel 1.8-mm diameter wires. Half-pin fixation had one metal-skin interface,
      whereas wire fixation had 2 interfaces. Patients were followed up every 2 weeks
      for 6 months. RESULTS: Of all 788 metal-skin interfaces, 143 (18%) were infected:
      72 (19%) of 371 in the diluted povidone-iodine group and 71 (17%) of 417 in the
      saline group. Dressing solution and patient age did not significantly affect
      infection rates. Half-pin fixation was more likely to become infected than wire
      fixation (25% vs 15%). CONCLUSION: Saline is as effective as diluted povidone
      iodine as a dressing solution for metal-skin interfaces of external fixators.
      Saline is recommended in view of its easy availability and lower costs.

PMID- 19398788
TI  - Unreamed intramedullary nailing with oblique proximal and biplanar distal
      interlocking screws for proximal third tibial fractures.
AB  - PURPOSE: To assess the outcome of unreamed intramedullary nailing through the
      lateralised entry point using oblique proximal and biplanar distal interlocking
      screws. METHODS: 15 men and 3 women aged 25 to 58 (mean, 37) years underwent
      unreamed intramedullary nailing with oblique proximal and biplanar distal
      interlocking screws for proximal third metaphyseal tibial fractures. The entry
      point was kept proximal to the tibial tuberosity and slightly lateral to midline.
      Proximal locking was at 45 degrees to the coronal and sagittal planes. Biplanar
      distal locking was in the coronal and sagittal planes. RESULTS: 16 patients had
      bone union within 20 (mean, 17; range, 14-27) weeks; 2 underwent dynamisation for
      delayed union. Three patients had valgus angulation of less than 5 degrees; 2 had
      a loss of terminal knee flexion; 3 had a loss of ankle dorsiflexion; and 3 had
      shortening of more than 0.5 cm. Functional outcomes were excellent in 13, good in
      4, and fair in one patient. No patient endured neurovascular injury, compartment
      syndrome or implant failure. CONCLUSION: Unreamed intramedullary nailing with
      oblique proximal and biplanar distal interlocking screws for proximal third
      tibial fractures was effective in preventing malalignment.

PMID- 19398789
TI  - Ligamentotaxis for Barton's and paediatric distal radial fractures.
AB  - PURPOSE: To establish a consensus regarding immobilisation of the wrist following
      reduction of Barton's and paediatric distal radial fractures. METHODS:
      Questionnaires were distributed to orthopaedic surgeons at the European
      Federation of National Associations of Orthopaedics and Traumatology meeting in
      Lisbon in 2005. Questions included the surgeon's country of practice, hospital,
      professional grade, years of experience, sub-specialty, and preferred position of
      wrist immobilisation after (1) a volar Barton's fracture, (2) a dorsal Barton's
      fracture, (3) a paediatric Salter-Harris type-II injury to the distal radius with
      volar displacement, and (4) the same injury but with dorsal displacement.
      RESULTS: Of 148 questionnaires distributed, 118 were returned. The specialist-to
      trainee ratio was 45:73. In volar Barton's fractures, only 20% (29% specialists
      and 15% trainees) would immobilize the wrist in palmar flexion, as per
      recommendations. In dorsal Barton's fractures, only 25% (33% specialists and 21%
      trainees) would immobilize the wrist in dorsiflexion, as per recommendation. In
      paediatric Salter Harris type-II injury to the distal radius with volar
      displacement, 87% (100% specialists and 79% trainees) would immobilize the wrist
      in dorsiflexion or in a neutral position, as per recommendation. In the same
      injury but with dorsal displacement, 84% (89% specialists and 81% trainees) would
      immobilize the wrist in palmar flexion or in a neutral position, as per
      recommendation. In all 4 types of fractures, 26% to 30% of respondents would
      immobilize the wrist in a neutral position. CONCLUSION: Most respondents deviate
      from the recommended immobilisation positions in treating Barton's fractures.
      Understanding of the anatomy or biomechanics of ligamentotaxis are crucial for
      conservative treatments.

PMID- 19398790
TI  - Use of suture anchors for coronoid fractures in the terrible triad of the elbow.
AB  - PURPOSE: To report outcomes in 6 patients with the terrible triad of the elbow
      treated with our modified protocol. METHODS: 6 men aged 26 to 54 years underwent
      surgery for the terrible triad of the elbow by a single surgeon. All the patients
      had a displaced comminuted fracture of the radius, posterior dislocation of the
      elbow, and Morrey type-I fracture of the coronoid. They all underwent replacement
      of the radial head and repair of the lateral collateral ligament to the isometric
      part of the lateral condyle using suture anchors. Five had an additional capsular
      fixation to the anterior coronoid using suture anchors; in patient 6 the coronoid
      was not repaired because it was stable. Functional outcomes were evaluated using
      the Hospital for Special Surgery (HSS) elbow assessment score. Bone union,
      implant loosening, heterotopic ossification, and degenerative changes were
      assessed using anteroposterior and lateral radiographs. RESULTS: After a mean
      follow-up of 2.2 (range, 1-3) years, the mean arc of flexion-extension was 116
      degrees and the mean flexion contracture was 15 degrees. All patients maintained
      a concentric reduction of both the ulnotrochlear and the radiocapitellar
      articulation, with isometric fixation of the lateral collateral ligament. No
      patient had dislocation of the radial-head prosthesis. All had good-to-excellent
      HSS elbow scores, and none required re-operation. Patient 2 had neuropraxia of
      the radial nerve, which recovered within 3 months. Patient 4 had a range of
      movement of only 20 to 100 degrees, but was satisfied with the outcome.
      CONCLUSION: Repair of the articular capsule using suture anchors in addition to
      replacement of the radial head and repair of the lateral collateral ligament
      achieves favourable outcome in patients with the terrible triad of the elbow.

PMID- 19398791
TI  - Total hip arthroplasty using proximal porous coating stem with distal sleeve: mid
      term outcome.
AB  - PURPOSE: To report mid-term results of total hip arthroplasty (THA) using the
      Opti-Fix Plus Hip System (Opti-Fix Hip), and to assess the correlations between
      peri-implant bone changes and the distal medullary occupancy rate. METHODS: 11
      men (13 hips) and 53 women (58 hips) aged 24 to 87 (mean, 61) years underwent THA
      using the Opti-Fix Hip, with a modular stem and a distal sleeve, and were
      followed up for a mean of 6.5 (range, 4.8-9.6) years. Clinical outcomes were
      evaluated using the Japanese Orthopaedic Association (JOA) hip score. Implant
      stability, bone changes around the implant, and the occupancy rate of the stem in
      the medullary space were examined radiologically. Bone changes around the implant
      were assessed based on the radiological evidence of a pedestal, osteolysis,
      stress shielding, and radiolucent lines. RESULTS: The mean JOA score increased
      significantly after surgery and was maintained at the latest follow-up. Around
      the acetabular and femoral components respectively, 38 and 58 hips had
      radiolucent lines, whereas one and 54 hips developed osteolysis. A pedestal
      appeared in 21 hips and grade-III or higher stress shielding in 30 hips. Two hips
      showed loosening of the acetabular components, but none in the femoral
      components. Osteolysis around the stem was frequently observed in hips with poor
      distal medullary occupancy. CONCLUSION: Clinical and radiological outcomes of the
      Opti-Fix Hip were favourable. The low incidence of osteolysis in the distal stem
      suggests that the proximal circumferential porous coating was effective. Minor
      osteolysis around the proximal stem was frequently observed, indicating early
      excessive wear of the polyethylene liner. Its high distal medullary occupancy
      rate could inhibit stem micromotion and aseptic loosening.

PMID- 19398792
TI  - Comparison of acetabular reamings during hip resurfacing versus uncemented total
      hip arthroplasty.
AB  - PURPOSE: To compare the quantity of bone removed from the acetabulum during
      resurfacing hip arthroplasty versus uncemented total hip arthroplasty (THA).
      METHODS: 62 consecutive patients with osteoarthritis of the hip were
      prospectively studied. 24 men and 7 women aged 40 to 86 (mean, 59) years
      underwent Birmingham hip resurfacing. 13 men and 18 women aged 34 to 88 (mean,
      61) years underwent uncemented THA using the trident acetabular cup. Obese
      elderly women at risk of femoral neck fracture and patients with large
      subchondral pseudocysts or a history of avascular necrosis of the femoral head
      were assigned to uncemented THA. Acetabular reamings were collected; marginal
      osteophytes were not included. The reamings were dehydrated, defatted, and
      weighed. RESULTS: The mean weight of acetabular reamings was not significantly
      different between patients undergoing hip resurfacing and uncemented THA
      (p=0.57). CONCLUSION: In hip resurfacing, the use of an appropriately small
      femoral component avoids oversizing the acetabular component and removal of
      excessive bone stock.

PMID- 19398793
TI  - Effects of positioning and notching of resurfaced femurs on femoral neck
      strength: a biomechanical test.
AB  - PURPOSE: To assess the effects of positioning and notching of resurfaced femurs
      on the mechanical strength of third-generation saw bone (TGSB) femurs using an in
      vitro analogue bone model. METHODS: 30 TGSB femurs were equally divided into 6
      resurfaced femur groups (intact, anatomic, varus, valgus, anatomically notched,
      and valgus notched) for testing the load to failure, stiffness, and total energy.
      RESULTS: Compared to the intact femurs, the load to failure in all resurfaced
      femurs was significantly decreased by 29 to 57%. Among the resurfaced femurs,
      valgus and anatomic femurs had the highest load to failure, followed by valgus
      notched, varus, and anatomically notched femurs. Notching weakened the construct
      by a further 24 to 30%. CONCLUSION: To minimise the risk of femoral neck
      fracture, resurfaced femoral heads should be placed in an anatomic or valgus
      orientation, and the superior cortex of the femoral neck should remain intact.

PMID- 19398794
TI  - Arthroscopy-assisted computer navigation in high tibial osteotomy for varus knee
      deformity.
AB  - PURPOSE: To assess the accuracy of knee alignment after high tibial osteotomy
      (HTO) for varus knee deformity using arthroscopy-assisted computer navigation.
      METHODS: Six men and 4 women aged 47 to 53 (mean, 49) years underwent medial open
      wedge HTO for varus knee deformity and medial unicompartmental osteoarthritis
      using arthroscopy-assisted computer navigation with fluoroscopy. Patients were
      followed up for a mean of 23 (range, 11-32) months. Intra- and post-operative leg
      alignments were compared. RESULTS: The mean postoperative coronal plane alignment
      was 2.7 (range,1-4) degree valgus; the mean deviation from intra-operative
      computer images was one (range, 0.1-1.9) degree; 5 knees had less valgus in the
      postoperative radiographs than the intra-operative computer images. CONCLUSION:
      Despite being more technically demanding, time consuming, and costly, arthroscopy
      assisted computer navigation is safe, accurate, and reliable for HTO.

PMID- 19398795
TI  - Cytokine synthesis by chondroblastoma: relation to local inflammation.
AB  - PURPOSE: To investigate cytokine production by chondroblastoma in inducing local
      inflammation and adjacent-joint arthritis. METHODS: Immunohistochemical analyses
      of curetted tissues using anti-human interleukin (IL)-1 beta, IL- 6, IL-8, and
      tumour necrosis factor (TNF)-alpha were performed for 6 patients with
      chondroblastoma and 3 patients with giant cell tumour (GCT) of bone. In addition,
      prostaglandin E2, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, and TNF-alpha in the
      cyst fluid of one of the patients with chondroblastoma and 2 with GCT of bone
      were measured using immunoassay kits. RESULTS: More positive staining for IL-1
      beta, IL-8, IL- 6, and TNF-alpha was shown in chondroblastoma than GCT of bone
      samples. Osteoclast-like giant cells in chondroblastomas showed positive staining
      for IL- 6 only. In addition, concentrations of IL-4, IL-6, and IL-8 in the cyst
      fluid were higher in the one patient with chondroblastoma than the 2 patients
      with GCT of bone. CONCLUSION: Cytokines such as IL-1 beta, IL-8, TNF-alpha, and
      particularly IL-6 play an important role in local inflammation in patients with
      chondroblastoma.

PMID- 19398796
TI  - Continuous decompression using a cannulated ceramic pin for simple bone cysts.
AB  - PURPOSE: To report the outcomes of continuous decompression using a cannulated
      ceramic pin for simple bone cysts (SBCs). METHODS: Seven boys and 3 girls aged 7
      to 16 (mean, 11) years with SBCs underwent curettage and continuous decompression
      using a cannulated ceramic pin. The pin was made of hydroxyapatite and tricalcium
      phosphate. The clinical course, radiological findings, and complications were
      retrospectively assessed. RESULTS: The mean follow-up duration was 41 (range, 12
      84) months. Five patients were evaluated as 'healed', 2 as 'healing with defect',
      one as 'persistent cyst', and 2 as 'recurrent cysts'. No peri-operative
      complications were encountered. One patient had a postoperative fracture at the
      pin insertion site. Seven patients had pain relief and good outcomes; 2 had a
      thin cortical rim and complained of occasional pain and their sports activities
      were restricted. CONCLUSION: Decompression using a cannulated ceramic pin for
      SBCs is minimally invasive, highly osteoconductive, and does not require bone
      grafting or a second operation to remove the device.

PMID- 19398797
TI  - Conservative management of idiopathic clubfoot: Kite versus Ponseti method.
AB  - PURPOSE: To compare the long-term results of the Kite and Ponseti methods of
      manipulation and casting for clubfoot. METHODS: 42 patients (with 64 idiopathic
      clubfeet) were equally randomised to Kite or Ponseti treatments in the early
      weeks of life. 14 males and 7 females (34 clubfeet) were treated by the Kite
      method, whereas 13 males and 8 females (30 clubfeet) were treated by the Ponseti
      method. All the clubfeet were manipulated, casted, and followed up (for a mean of
      3 years) by one experienced orthopaedic surgeon. The final results were compared.
      RESULTS: The success rates for the Kite and Ponseti treatments were similar (79%
      vs 87%). With the Ponseti method, the number of casts was significantly fewer (7
      vs 10); the duration of casting required to achieve full correction was
      significantly shorter (10 vs 13 weeks); the maximum ankle dorsiflexion achieved
      was significantly greater (12 vs 6 degrees); and the incidence of residual
      deformity and recurrence was slightly lower. CONCLUSION: The Ponseti method can
      achieve more rapid correction and ankle dorsiflexion with fewer casts, without
      weakening the Achilles tendon.

PMID- 19398798
TI  - Review article: Glucosamine.
AB  - It has been claimed that glucosamine is able to alleviate pain, slow down losses
      of, and even restore articular cartilage in patients with damaged or
      osteoarthritic joints. It is classified as a food additive or nutraceutical;
      therefore manufacturers do not need to comply with the same regulations that
      apply for quality assurance within the pharmaceutical industry. Osteoarthritis
      can be managed by pharmacological and non-pharmacological methods. It is
      controversial whether glucosamine sulphate is the first structure-modifying drug
      commercially available. Little evidence suggests that glucosamine is superior to
      a placebo treatment in restoring articular cartilage.

PMID- 19398799
TI  - Review article: Validity of the KT-1000 knee ligament arthrometer.
AB  - The KT-1000 knee arthrometer (KT-1000) is an objective instrument to measure
      anterior tibial motion relative to the femur for anterior cruciate ligament (ACL)
      reconstruction. Four studies between 1950 and 2007 regarding validity of the KT
      1000 were identified using a Medline search. One had interpretable information on
      sensitivities, specificities, and predictive values to validate the instrument as
      a diagnostic tool in patients with acute or chronic ACL injuries. Three had
      limitations in methodology. We suggest that the KT-1000 should be used with
      caution as an objective instrument. Rather, using a KT-1000 score derived by
      subtracting the anterior tibial motion relative to the femur of the injured knee
      to that of the uninjured knee may be more appropriate as a dichotomous diagnostic
      test with a threshold of 2 or 3 mm.

PMID- 19398800
TI  - Facet cyst haematoma in the lumbar spine: a report of four cases.
AB  - We present 4 cases of facet cyst haematoma in the ligamentum flavum of the lumbar
      spine. All patients presented with a one-to-3-month history of back pain or
      numbness in the legs, and sudden neurological deterioration. One also developed
      cauda equina syndrome and another developed radiculopathy. In all cases, magnetic
      resonance imaging showed a mass with high signal intensity on both T1- and T2
      weighted images. Facet arthrography and computed tomography revealed
      communication between the mass and the neighbouring facet joint. The haematomas
      were removed en bloc with the ligamentum flavum. They were surrounded by the
      ligament and contained degenerated and lacerated elastic fibres but no synovial
      lining cells. Facet cyst haematoma is so-named because of bleeding from tissue
      adjacent to the facet joint into a pre-existing facet cyst.

PMID- 19398801
TI  - Posterior lumbar apophyseal ring fractures in adolescents: a report of four
      cases.
AB  - Posterior lumbar apophyseal ring fractures are rare in adolescents. We report 4
      such cases in Chinese adolescents. Two of the patients had a slipped capital
      femoral epiphysis; 3 of them were overweight/obese. All presented with low back
      pain and radicular pain. Apophyseal fractures of the upper lumbar spine usually
      involve the lower end plate, whereas those of the lumbar sacral spine usually
      involve the upper end plate. The radiological features and pathophysiology are
      discussed. Two of the patients were treated with laminotomy and diskectomy after
      conservative treatment failed. All patients had complete resolution of their
      neurological deficits at a mean follow-up of 2 years. Despite its benign nature,
      long-term follow-up is necessary to define the natural course and prognosis of
      the disease. A high index of suspicion is needed to diagnose these fractures in
      adolescents.

PMID- 19398802
TI  - Spinal cord compression secondary to brown tumour in a patient on long-term
      haemodialysis: a case report.
AB  - Brown tumours may occur secondary to hyperparathyroidism in patients with chronic
      renal failure (CRF). Diagnosing a spinal brown tumour causing cord compression
      requires a high index of suspicion. We report a 65-year-old woman, who had been
      on haemodialysis for CRF for over 10 years, who presented with leg weakness and
      back pain over the thoracolumbar junction. She had a brown tumour at T8 causing
      subacute spinal cord compression. Ambulation was regained after surgical
      decompression and stabilisation. Adherence to the National Kidney Foundation
      guidelines in the management of patients with CRF may prevent renal
      osteodystrophy. Treatment of spinal brown tumour depends on the severity of the
      neurological deficit. Remineralization is expected after correction of the
      parathyroid level, thus negating the need for total excision of the parathyroid
      glands.

PMID- 19398803
TI  - Botulinum toxin type A for rehabilitation after a spinal cord injury: a case
      report.
AB  - A 56-year-old man became quadriplegic, bed bound, and carer-dependent secondary
      to cervical osteomyelitis. Three years later, he presented with generalised
      spasticity, crouched posture, and a large sacral pressure sore. The severe
      spasticity in his hips and knees prevented ischial sitting. Injections of
      botulinum toxin type A to both hamstrings and gastrosoleuii controlled the flexor
      spasticity of his lower limbs and facilitated rehabilitation and wound healing
      through proper positioning, wound care, stretching, and weight-bearing exercises.
      A few weeks later, the patient could better position himself in bed (prone lying)
      and on his wheelchair (ischial sitting). His spasm-related pain lessened and his
      mobility and activities of daily living improved. The sacral pressure sore healed
      completely a few months later. The patient could sleep better, feed with set-up
      and adaptive aids, groom, dress, and transfer himself with minimal assistance.
      The effects of botulinum toxin extended beyond just spasticity reduction. His
      upper extremity function, mobility, and social well-being were all improved
      through better positioning.

PMID- 19398804
TI  - Haemodynamic instability secondary to minimally displaced pubic rami fractures: a
      report of two cases.
AB  - We report 2 patients with haemodynamic instability secondary to minimally
      displaced pubic rami fractures following a fall. Both complained of pain and
      swelling in the abdomen and groin, and had abdominal distension and bruising in
      the abdomen, groin, and perineum. All these may be early signs of severe vascular
      injury and should be treated promptly. Both patients were treated with
      embolisation of the injured vessels using emergency angiography.

PMID- 19398805
TI  - Infectious arthritis of the knee caused by Mycobacterium terrae: a case report.
AB  - Mycobacterium terrae is ubiquitous in our environment. M terrae infections most
      commonly involve tendon sheaths, bones, bursae, and joints. We report a case of
      infectious arthritis of the knee caused by M terrae in a 21-year-old man who had
      non-specific chronic synovitis. No organism was seen on microscopy or isolated
      from cultures until months later. Initially the M terrae culture was considered a
      contaminant and specific anti-mycobacterial treatment was not advised. The
      patient was commenced on suppressive therapy for persistent effusion and
      discomfort. Eventually, the M terrae infection was confirmed and he was commenced
      on clarithromycin, ciprofloxacin, and ethambutol. The triple antibiotic regimen
      was continued for 2 years. The knee improved but never completely settled. The
      patient chose to cease all antibiotic medication. The knee remained swollen and
      irritable, with little chance of eradicating the organism.

PMID- 19398806
TI  - Traumatic dislocations of the proximal tibiofibular joint: a report of two cases.
AB  - Traumatic dislocations of the proximal tibiofibular joint are rare and difficult
      to diagnose. They can present as an isolated case or in association with multiple
      injuries. They are typically classified into subluxation, anterolateral,
      posteromedial, and superior dislocations. We report 2 unusual dislocations
      (posterolateral and inferior) of the proximal tibiofibular joint, both associated
      with floating knee injuries. Their diagnoses are mainly based on the presence of
      neurovascular injuries.

PMID- 19398807
TI  - Open reduction and internal fixation for concomitant talar neck, talar body, and
      medial malleolar fractures: a case report.
AB  - Fractures of the talus are rare and generally associated with severe trauma. The
      mechanism of injury is usually forced dorsiflexion or a fall from a height.
      Severe talar fractures pose a challenge for surgeons as they are often associated
      with complications such as avascular necrosis, collapse, malunion, secondary
      osteoarthritis and pain. This has led some institutions to advocate primary
      arthrodesis for these injuries. We report an unusual complex fracture of the
      talus that was successfully managed with open reduction and internal fixation. By
      restoring a near-normal range of motion and function to a fit, young male, the
      severely limiting effects of arthrodesis were avoided or at least delayed. We use
      this case to highlight that primary arthrodesis should only be reserved for cases
      that fail to respond to open reduction and internal fixation or deteriorate to
      the point where it is the only reasonable and justifiable alternative.

PMID- 19398808
TI  - Reconstruction of the Achilles tendon and overlying soft tissue using an
      anteromedial thigh flap for a post-burn pes equinus deformity: a case report.
AB  - We present a 36-year-old man with a severe pes equinus deformity of the ankle and
      an intractable ulcer over the Achilles tendon after a 4th-degree burn. He
      underwent a one-stage reconstructive surgical procedure using an anteromedial
      thigh flap with its vascularised fascia. After lengthening of the Achilles tendon
      and posterior release of the ankle, the anteromedial thigh fasciocutaneous flap
      was transferred. The ischaemic Achilles tendon was wrapped with the vascularised
      femoral fascia for vascularisation and reinforcement. The skin defect was covered
      with the skin paddle of the combined flap. There were no postoperative
      complications. At the 3-year follow up, the range of movement of the ankle was
      almost normal. The patient was able to walk and climb stairs without support, and
      the ulcer was cured.

PMID- 19398809
TI  - Chronic recurrent multifocal osteomyelitis of the first metatarsal bone: a case
      report.
AB  - We report a case of chronic recurrent multifocal osteomyelitis in a 9-year-old
      girl. She presented with a 9-month history of gradually worsening pain and
      swelling in her left foot. Non-steroidal anti-inflammatory drugs were prescribed
      but the symptoms persisted. She underwent curettage through a small oval
      corticotomy window on the first metatarsal bone. The pain and swelling improved
      promptly and she was able to walk without pain 2 weeks later. Curettage enabled
      rapid symptomatic relief and induced remission, with little risk of
      complications.

PMID- 19398810
TI  - Tubercular osteomyelitis of the clavicle: a report of four cases.
AB  - We report the clinicoradiological features of tuberculosis in the clavicle in 4
      patients. The patients' ages ranged from 9 months to 29 years. All patients were
      managed with antitubercular drug therapy for one year and one underwent surgical
      debridement and curettage as well. Clinicians should be aware of the varied
      presentation (pain, non-healing ulcer, abscess, multifocal osteoarticular
      tuberculosis) of this condition. With the worldwide resurgence of tuberculosis,
      clinicians should maintain a high index of suspicion. The diagnosis of
      osteoarticular tuberculosis is usually made on clinico-radiological features.

PMID- 19398811
TI  - Pigmented villonodular synovitis of the elbow with a fenestrated fossa: a case
      report.
AB  - We report a case of pigmented villonodular synovitis of the elbow in a 55-year
      old woman. Its radiological feature, the fenestrated fossa, may be characteristic
      of the advanced stage of this disorder.

PMID- 19398813
TI  - Comment on 'Non-invasive monitoring of chewing and swallowing for objective
      quantification of ingestive behavior'.
AB  - The paper of Sazonov et al (2008 Physiol. Meas. 29 525-41) addresses the topic of
      on-body sensor-based measurement and analysis of food intake and eating
      behaviour. The authors rightly pinpoint a lack of solutions to estimate eating
      behaviour and energy intake in contrast to the active development of energy
      expenditure prediction tools. Unfortunately, Sazonov and colleagues have missed
      reviewing a considerable amount of published research in the field of ubiquitous
      and wearable computing. Moreover, it should be noted that objective measurement
      techniques exist for laboratory studies of chewing and swallowing that could have
      served for the validation of their work. This letter summarizes relevant related
      works and identifies refinements of the study methodology suggested by Sazonov et
      al. Food intake behaviour is very variable and hard to capture. Nevertheless, the
      approaches towards automatic dietary monitoring (ADM) cited in this letter
      confirm the broad potential for sensing and pattern recognition techniques. ADM
      could eventually supplement or replace intake diaries.

PMID- 19398814
TI  - Electrical impedance spectroscopy as a potential tool for recovering bone
      porosity.
AB  - This paper deals with the recovery of porosity of bone from measurements of its
      effective electrical properties. The microstructural information is contained in
      the spectral measure in the Stieltjes representation of the bone effective
      complex permittivity or complex conductivity and can be recovered from the
      measurements over a range of frequencies. The problem of reconstruction of the
      spectral measure is very ill-posed and requires the use of regularization
      techniques. We apply the method to the effective electrical properties of
      cancellous bone numerically calculated using micro-CT images of human vertebrae.
      The presented method is based on an analytical approach and does not rely on
      correlation analysis nor on any a priori model of the bone micro-architecture.
      However the method requires a priori knowledge of the properties of the bone
      constituents (trabecular tissue and bone marrow). These properties vary from
      patient to patient. To address this issue, a sensitivity analysis of the
      technique was performed. Normally distributed random noise was added to the data
      to simulate uncertainty in the properties of the constituents and possible
      experimental errors in measurements of the effective properties. The values of
      porosity calculated from effective complex conductivity are in good agreement
      with the true values of bone porosity even assuming high level errors in the
      estimation of the bone components. These results prove the future potential of
      electrical impedance spectroscopy for in vivo monitoring of level and treatment
      of osteoporosis.

PMID- 19398815
TI  - Optimizing leaf widths for a multileaf collimator.
AB  - The multileaf collimator (MLC) is becoming a standard accessory of modern linac
      in shaping radiation fields. However, for a given target (projection), the
      radiation field shaped by an MLC has a stepwise boundary and is not identical to
      the desired field that exactly conforms to the target. That means there are
      always under-blocked and/or over-blocked areas. The total area of discrepancy
      depends on MLC leaf widths. The purpose of this study is to develop an
      optimization model for determining leaf widths so that the total area of
      discrepancy between MLC-shaped fields and the desired ones can be minimized. The
      optimization model regards leaf widths as variables, the total area of
      discrepancy between MLC-shaped fields and the desired fields as an objective
      function, and the total width of all leaves as a constraint. A problem described
      by the model is solved with the hybrid of a simulated annealing technique (ASA,
      Lester Ingber, 1993) and a gradient technique (DONLP2, P Spellucci, 2001). The
      performance of the optimization model was evaluated on 634 target fields
      continuously selected from the patient database of a treatment planning system.
      The lengths of these fields ranged from 3.9 to 38.7 cm and had an average of 15.3
      cm. The total area of discrepancy was compared between an MLC with optimal leaf
      widths and a conventional MLC with the same number of leaf pairs. Optimal leaf
      widths were obtained for an MLC with total leaf pairs of 28, 40 and 60,
      respectively, which corresponded to three types of conventional MLCs. The optimal
      leaf width first decreases slightly and then nonlinearly increases with the
      distance away from the central line. Compared with the MLC with conventional leaf
      width arrangement, the MLCs with optimal leaf width arrangement reduced the total
      area of discrepancy by 11.1%, 28.6% and 25.0%, respectively. Optimizing leaf
      widths can either improve the conformity of MLC-shaped fields to the treatment
      targets when the number of leaf pairs does not change, or reduce the number of
      leaf pairs without sacrifice of field conformity.

PMID- 19398816
TI  - Development of a remanence measurement-based SQUID system with in-depth
      resolution for nanoparticle imaging.
AB  - We present a remanence measurement method using a superconducting quantum
      interference device (SQUID) to detect trace amounts of magnetic nanoparticles
      (MNPs). Based on this method, a one-dimensional scanning system was established
      for imaging. The system was calibrated with 25 nm diameter Fe2O3 nanoparticles
      (NPs), and the sensitivity of the NPs was found to be 10 ng at a distance of 1.7
      cm and the spatial resolution was approximately 1 cm. A theoretical model of this
      system was developed and applied to the deconvolution of scanned images of
      phantoms with two NP injection spots. Using the developed SQUID system, we were
      able to determine not only the amount and horizontal positions of the injections,
      but also their depths in the phantoms.

PMID- 19398817
TI  - Beam hardening correction in CT myocardial perfusion measurement.
AB  - This paper presents a method for correcting beam hardening (BH) in cardiac CT
      perfusion imaging. The proposed algorithm works with reconstructed images instead
      of projection data. It applies thresholds to separate low (soft tissue) and high
      (bone and contrast) attenuating material in a CT image. The BH error in each
      projection is estimated by a polynomial function of the forward projection of the
      segmented image. The error image is reconstructed by back-projection of the
      estimated errors. A BH-corrected image is then obtained by subtracting a scaled
      error image from the original image. Phantoms were designed to simulate the BH
      artifacts encountered in cardiac CT perfusion studies of humans and animals that
      are most commonly used in cardiac research. These phantoms were used to
      investigate whether BH artifacts can be reduced with our approach and to
      determine the optimal settings, which depend upon the anatomy of the scanned
      subject, of the correction algorithm for patient and animal studies. The
      correction algorithm was also applied to correct BH in a clinical study to
      further demonstrate the effectiveness of our technique.

PMID- 19398818
TI  - Obsessive-compulsive disorder.

PMID- 19398819
TI  - Clinical screening for obsessive-compulsive and related disorders.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD)
      and other OCD-related disorders (OCDs) are frequently overlooked during medical
      or even psychiatric evaluation. Individuals with affective disorders, anxiety
      disorders, eating disorders, alcohol abuse and schizophrenia are commonly
      affected. Increased prevalence of OCDs is also reported to occur in certain
      secondary health-care settings. Better identification and treatment of OCDs are
      increasingly recognized as important public health priorities. METHOD: In this
      narrative review we consider the arguments for the use of screening strategies
      for OCD in clinical practice, paying particular attention to pragmatic issues
      such as the shortage of suitable screening instruments and areas of medical
      practice where screening might most profitably be exercised. RESULTS: Arguments
      for screening in fields where affected individuals congregate appear persuasive,
      although evidence that screening produces clinical and social benefits by
      reducing morbidity is still lacking. CONCLUSION: Confirmation of health-care
      settings attracting high concentrations of OCD and BDD and evaluation of specific
      screening instruments and their utility in reducing the burden of disease are
      important areas for future research. Further evaluation of the validity and
      reliability of specific screening tools across different clinical populations is
      required.

PMID- 19398820
TI  - Cluster analysis of obsessive-compulsive symptomatology: identifying obsessive
      compulsive disorder subtypes.
AB  - BACKGROUND: There is increasing evidence that obsessive-compulsive disorder (OCD)
      is a heterogeneous disorder. Different clinical subtypes may be characterized by
      differing pathophysiological mechanisms and treatment outcomes. METHODS: A
      cluster analysis was performed on 45 items of the Yale-Brown Obsessive-Compulsive
      Symptoms Checklist (YBOCS-CL) for 261 patients with OCD. Cluster solutions
      emerging at different linkage distance levels, and the associations of identified
      clusters with demographic, clinical and relevant genetic variables, were
      investigated. RESULTS: A 6-cluster solution emerged at a linkage distance level
      of 1.5, and a 3-cluster solution emerged at a linkage distance level of 2.1. The
      3 clusters in the latter solution were labeled I) Contamination / washing, II)
      Hoarding / symmetry / ordering, and III) Obsessional / checking. Increased
      Cluster III scores were associated with earlier age of OCD onset and the Met/Met
      (L/L) genotype of the COMT Val158Met polymorphism. CONCLUSION: The data here are
      consistent with previous work delineating the different symptom subtypes of OCD,
      also with previous work suggesting that the Met/Met (L/L) genotype of the COMT
      Val158Met polymorphism may be associated with anxiety symptoms, as well as with
      previous work suggesting that dopaminergic genes may be particularly important in
      early-onset OCD.

PMID- 19398821
TI  - Relationship between childhood sexual abuse and obsessive-compulsive disorder:
      case control study.
AB  - BACKGROUND: The psychiatric sequelae of childhood sexual abuse (CSA) is
      associated with a variety of psychiatric disorders, such as eating disorders,
      depression, posttraumatic-stress disorder and borderline personality disorder.
      This study examined the association of CSA and obsessive-compulsive disorder
      (OCD) in adults. METHODS: Frequency of CSA was examined among 30 OCD patients and
      in two control groups: 17 patients with panic disorder (PD) and 26 non
      psychiatric rheumatic patients (NPRP). Study tool was a semi-structured
      interview. RESULTS: A significantly higher frequency of CSA involving physical
      contact was found among the OCD (53.3%) and PD patients (52.9%) as compared to
      NPRP (23.1%). No significant differences were found in the frequencies of non
      contact CSA. LIMITATIONS: Differences could partially be attributed to the
      tendency of psychiatric patients to provide personal information, especially when
      motivated to pinpoint an external factor for their illness. CONCLUSIONS: A
      positive association was found between contact-CSA and OCD as well as PD.While it
      is not definitely clear whether CSA is a unique entity or has influence similar
      to any other stressful life event, the findings of this study support further
      investigation of the role of contact CSA in OCD and PD, as well as in other
      psychiatric disorders.

PMID- 19398822
TI  - Ultra-orthodox rabbinic responses to religious obsessive- compulsive disorder.
AB  - This presentation deals with the response of rabbis to ultra-orthodox people
      suffering from religious symptoms of obsessive-compulsive disorder. The symptoms
      are consistent with religious practice and patients justify their compulsive
      behaviors by the dictates of the codes of law.Will rabbis see their primary role
      as protection of the codes of law rather than alleviation of the suffering of the
      faithful? Will they see the person as someone who is meritoriously meticulous or
      in need of help? The writings of two eminent rabbis, and advice related by
      contemporary patients in Jerusalem, Israel are presented. The most arresting
      example of guidance is provided by Rabbi Nahman of Bratslav (1772-1810) who
      declared that he himself suffered from excessive religious practices typical of
      religious OCD until he overcame them. The accounts of rabbis and patients have
      features similar to the cognitive-behavioral treatment of choice for this
      disorder. The guidance of a rabbi is based on authority, and detailed knowledge
      of religious law, while a mental health therapist is an expert on OCD. The latter
      cannot give religious guidance, and has no authority within the ultra-orthodox
      community, and is only afforded a role with the rabbi's acquiescence. The role of
      the patient's rabbi is likely to be crucial in management. Religious guidance
      without professional help may often only have short-term benefit in this
      generally chronic condition, although studies have not been carried out.

PMID- 19398823
TI  - Intensive outpatient treatment for obsessive-compulsive spectrum disorders.
AB  - Exposure and response prevention (ERP) is the most effective treatment for
      obsessive-compulsive disorder (OCD), yet the intensive treatment schedule often
      described and recommended is not readily accessible to many populations. In the
      present article, the authors describe a time-limited, outpatient, intensive
      treatment for Obsessive Compulsive Spectrum Disorders in Israel. Working in the
      client's natural environment and making use of technology are particularly
      highlighted.

PMID- 19398824
TI  - Relative perceptions of the needs of inpatients with schizophrenia and
      schizoaffective disorders.
AB  - BACKGROUND: Although there is a consensus that mental health services should be
      provided on the basis of need, the concept of client needs differs substantially
      among professionals, patients and involved family members. The aim of the present
      study was to identify the needs of patients repeatedly hospitalized with
      schizophrenia and schizoaffective disorders and to compare them with the needs
      rated by their nursing staff and relatives. METHOD: Using the Camber well
      Assessment of Need (CAN), we surveyed 52 consecutive voluntarily re-admitted
      inpatients aged 18- 65 fulfilling the ICD-10 criteria for schizophrenia and
      schizoaffective disorders. Analysis of variance and post-hoc t-test single
      comparisons were performed to examine the between-groups differences in the
      number of unmet needs rated by patients, clinical staff and family members.
      RESULTS: Significant differences in the perceptions of the patients and staff
      occurred in only 6 of the 22 CAN domains, with the patients rating higher the
      needs for "information on condition and treatment" and "benefits," and the staff
      member rating higher the patients' needs for "intimate relationships,"; "safety
      for others," "self-care" and "daytime activities." The analogical differences
      occurred between the patients and their relatives in the same need areas.
      CONCLUSIONS: Comparing the needs assessments from different perspectives provides
      a powerful means of patient evaluation and is potentially valuable information
      for care planning.

PMID- 19398825
TI  - Stigma experienced by persons under psychiatric care.
AB  - Mental health-related stigma causes suffering and interferes with care and social
      inclusion. This study explored stigma as experienced by mental health service
      users. Particular attention is given to their use of coping mechanisms.
      Interviews were held with 167 adults undergoing outpatient psychiatric treatment;
      two-thirds of them had previously been hospitalized. Examples of frequency of
      stigma-related situations included the following: Over half of service users
      expect people to refuse to have a person with a mental disorder as a co-worker or
      neighbor, or to engage in other types of social contact. A sizeable group
      acknowledged that they feared or had experienced rejection. A third of
      respondents reported they feared or had experienced inappropriate treatment by
      their doctor. Service users utilize several coping mechanisms to deal with
      stigma, among them: education, withdrawal, secrecy, and positive distinctiveness.
      Although we studied a convenience sample of service users, our findings provide
      sufficient basis to suggest different types of intervention, i.e., to address
      stigma in the course of treatment in the specialist settings, to promote the
      establishment of mutual support groups, and to raise family physicians' awareness
      with regard to the stigma that may be present when caring for persons with mental
      disorders.

PMID- 19398826
TI  - Clozapine in treatment-refractory obsessive-compulsive disorder with comorbid
      schizotypal personality disorder.

PMID- 19398827
TI  - [Bone fracture and the healing mechanisms. Pathophysiology and classification of
      osteoporotic fractures].
AB  - Bone provides momentary strength and fatigue strength, and bone strength
      decreases with age. In elderly men and women with fragile bones osteoporotic
      fractures frequently occur. Fragility fracture occurs as a consequence of the
      decrease in momentary strength, and fragility fracture is one of the pathological
      fractures. In patients with the decrease in fatigue strength, insufficiency
      fractures frequently occurs. Insufficiency fracture is the same term as stress or
      fatigue fracture.

PMID- 19398829
TI  - [Bone fracture and the healing mechanisms. Molecular bases of fracture healing].
AB  - Fracture healing is a process comprising of a local bleeding followed by
      inflammation and differentiation of mesenchymal cells that lead to formation of
      soft extracellular matrix tissue, cartilage and bone. This pathway includes endo
      chondral bone formation and in part intra-membranous bone formation. During this
      process several sets of cytokines are involved in the regulation of the progress
      in fracture healing. This paper reviews the molecules involved in fracture
      healing.

PMID- 19398828
TI  - [Bone fracture and the healing mechanisms. Histological aspect of fracture
      healing. Primary and secondary healing].
AB  - It is quite important to understand the histological aspect of fracture healing.
      It is helpful in the clinical practice to recognize how fracture management
      induces biological reaction. Repair process is classified into primary and
      secondary fracture healing. Primary healing is direct bone repair without
      endochondral ossification, which includes cartilaginous callus formation. This
      pattern does not usually happen in the natural process of fracture healing. Bone
      remodeling initially occurs under the stable condition of fracture with rigid
      fixation and no gap formation. The key of this process is Haversian canal
      remodeling and reestablishment of blood vessels. Secondary healing is typically
      characterized by three overlapping stages: the initial inflammatory response,
      callus formation (soft and hard callus), initial bony union and bone remodeling.
      Most of fracture repair in the clinic follow this process, and callus formation
      is confirmed with X-ray. The key of this process is the appropriate stability of
      the fracture site to maintain biological healing response.

PMID- 19398830
TI  - [Bone fracture and the healing mechanisms. The mechanical stress for fracture
      healing in view of distraction osteogenesis].
AB  - It is generally accepted that moderate mechanical stress influences the course of
      fracture healing. A flexible fixation of the fractured site can induce fracture
      callus formation, whereas an unstable fixation can lead to a nonunion. The
      relationship between mechanical stress and the process of bone regeneration or
      healing remains incompletely understood. Distraction osteogenesis is a surgical
      technique that, using appropriate mechanical tension-stress, does not break the
      callus but rather it stimulates and maintains osteogenesis. The common principles
      of distraction osteogenesis are osteotomy and slow progressive distraction by an
      external fixation device. Interest in bone regeneration associated with
      mechanical stress might lead to better understanding of the fracture healing
      process.

PMID- 19398831
TI  - [Bone fracture and the healing mechanisms. Metabolic bone disease and skeletal
      healing].
AB  - We described about skeletal healing in metabolic bone diseases. Fracture healing
      in osteoporosis was not well investigated basically and clinically. Clinical
      research is difficult because fracture healing is affected by underlined disease
      causing osteoporosis and medication for osteoporosis. Recent basic research using
      ovariectomized model revealed delayed callus formation and decreased callus
      strength. As for osteomalacia, callus formation was delayed, and to correct the
      calcium and phosphate balance using vitamin D or phosphate improve the fracture
      healing and mineralization. As for osteopetrosis, fracture healing was delayed,
      but in most cases healing could be achieved finally non-operatively. Femoral neck
      fracture and coxa vara deformity should be considered to treat operatively.

PMID- 19398832
TI  - [Bone fracture and the healing mechanisms. Fibroblast growth factor-2 and
      fracture healing].
AB  - Fibroblast growth factor-2 (FGF-2) is a crucial regulator of bone metabolism with
      strong stimulatory effects on both bone formation and resorption. The potent bone
      anabolic action of FGF-2 has been demonstrated in several animal models including
      rodents and non-human primates. Our recent clinical trial has revealed that
      recombinant human (rh) FGF-2 in gelatin hydrogel dose dependently accelerated
      bone union of a surgical osteotomy with an excellent safety profile, suggesting
      the efficacy of this agent for bone repair.

PMID- 19398833
TI  - [Bone fracture and the healing mechanisms. The effect of human parathyroid
      hormone on fracture healing].
AB  - We reviewed the effect of human parathyroid hormone (hPTH) on fracture healing.
      In rodent fracture model, intermittent treatment of PTH accelerated the healing
      process as evidenced by earlier replacement of woven bone to lamellar bone,
      increased new cortical shell formation, and increased the ultimate load. In
      cynomolgus monkey fracture model, PTH accelerates the natural fracture healing
      process by shrinking callus size and increasing degree of mineralization of the
      fracture callus, thereby restoring intrinsic material properties.

PMID- 19398834
TI  - [Bone fracture and the healing mechanisms. The role of BMP signaling in fracture
      healing].
AB  - When bone tissue, which plays a central role in locomotive organs, is broken by
      trauma and decreased in its own function of support, it is lead to be remarkable
      decline in the activity of daily life (ADL). Recently, in a clinical situation,
      various treatments have been tried for prophylaxis of fractures, and these
      treatments have been rewarded with good results. However, fractures would be
      occurred in a certain amount and there would be serious problems in ADL if the
      treatment fails to repair fractures. Furthermore, fractures could spontaneously
      heal in several weeks, it can be achieved in early rehabilitation and improvement
      of ADL, if we can accelerate fracture healing. Bone morphogenetic proteins, which
      were advocated by Dr. Urist, would be expected to be a key to establish much
      better society especially for the old.

PMID- 19398835
TI  - [Bone fracture and the healing mechanisms. The effects of anti-resorptive agents
      on fracture healing].
AB  - The effects of anti-resorptive agents on fracture healing were reviewed based on
      the results of our studies using rats and cynomolugus monkeys. Anti-resorptive
      agents delay natural fracture healing process due to suppressed callus remodeling
      in response to the extent of remodeling suppression although they never interfere
      bone union or strength of fracture site. Bisphosphonates can increase the
      strength of fracture site by dramatically increasing callus volume, however they
      delay callus remodeling of woven bone into lamellar bone, which is structurally
      and mechanically superior to woven bone. This suggests that delayed natural
      fracture healing process caused by bisphosphonates was compensated by increased
      callus volume of immature bone.

PMID- 19398836
TI  - [Bone fracture and the healing mechanisms. A new method for evaluation of
      fracture healing by echo tracking].
AB  - Assessment of bone healing on radiographs is not necessarily objective. A
      clinical system was developed to quantify the stiffness of healing fractures of
      the tibia in patients by the echo tracking (ET) method in a manner similar to a
      three-point bending test. The lower leg was supported. An ultrasound probe was
      placed on the proximal and distal fragments and a load of 25 N was applied. With
      a multiple ET system, two probes measured the displacement of five tracking
      points on each of the proximal and distal fragments of the tibia, thereby
      detecting the bending of the two fragments generated by the load. ET angle was
      defined as the sum of the inclinations of the proximal and distal fragments.
      Patients with tibial fracture treated by a cast or internal fixation were
      measured over time. In patients with radiographically normal healing, the bending
      angle decreased exponentially over time. However, in patients with nonunion, the
      angle remained the same over time. It was demonstrated that the ET method could
      be clinically applicable to evaluate fracture healing as a versatile,
      quantitative and noninvasive technique.

PMID- 19398837
TI  - [Bone fracture and the healing mechanisms. Fragility fracture and bone quality].
AB  - Fracture occurs in bone having less than normal elastic resistance without any
      violence. Numerous terms have been used to classify various types of fractures
      from low trauma events; "fragility fracture", "stress fracture", "insufficiency
      fracture", "fatigue fracture", "pathologic fracture", etc. The definitions of
      these terms and clinical characteristics of these fractures are discussed. Also
      state-of-the-art bone quality assessments; Finite element analysis of clinical CT
      scans, assessments of the Microdamage, and the Cross-links of Collagen are
      introduced in this review.

PMID- 19398838
TI  - [Bone fracture and the healing mechanisms. Microdamage and Microfracture].
AB  - Although both microfracture and microdamage are the damages caused by bone
      fatigue, microfracture shows micro-callus formed during trabecular fracture
      healing. Microdamage shows microcracking in the bone matrix, which is detected by
      osteocyte network then repaired by bone remodeling. Imbalance between generation
      and repair of bone fatigue causes accumulation of microdamage.

PMID- 19398839
TI  - [Bone fracture and the healing mechanisms. Fracture treatment by low-intensity
      pulsed ultrasound].
AB  - The principles of fracture treatment are the reduction and fixation of the
      fracture site, while the subsequent biological healing process is expected.
      Currently, some treatment options that actively stimulate the repair reaction at
      the fracture site are either available, or they are soon going to become
      available for clinical use. Low-intensity pulsed ultrasound (LIPUS) or local
      growth factors are examples of these modalities. They are non-invasive or less
      invasive than the previous stimulating options such as bone grafting at the
      fracture site. These treatment modalities are not only used to heal delayed union
      or non-union but they also have the potential to shorten the repair period until
      union is achieved while also reducing complications, including deformity or non
      union.

PMID- 19398840
TI  - [Bone fracture and the healing mechanisms. Fracture treatment using electrical
      stimulation].
AB  - In 1953, Iwao Yasuda reported on the piezoelectricity of bone and the electrical
      stimulation of callus formation. Subsequently, various methods of electrical
      stimulation have been investigated, and the enhancement of callus formation by
      electrical stimulation is likely to have broad clinical applications for not only
      the repair of fractures, but also for nonunion and pseudoarthrosis. Recently,
      these outcomes have been validated by significant double blind clinical trials,
      and the electrical currents in bone were investigated at the molecular level.
      Moreover, the application of impedance measurements obtained upon electrical
      stimulation as a means to evaluate bone maturation was examined. This paper
      reports on the current methods of electrical stimulation, the fundamental effects
      on bone formation, and further clinical applications.

PMID- 19398841
TI  - [Bone fracture and the healing mechanisms. Application of the extracorporeal
      shock wave on treatment of fracture].
AB  - We developed a new and unique extracorporeal shock waves (ESW) generator for bone
      application in 1992. ESW was applied to the canine's femurs. Gross fracture was
      not seen in any of the dogs. Detachment of the periosteum and subperiosteal
      bleeding were seen. Callus formation was seen beneath the periosteum at the
      focusing surface of the cortex and inner surface of the cortex. We applied ESW to
      eight patients with delayed union of the fracture. The sites of the ESW
      application were 4 tibiae, 2 humerus, one radius, one femur. ESW was applied to
      the delayed union site avoiding a metal plate, major vessels, and peripheral
      nerves. Five out of 8 cases achieved bone union. Average period until fusion
      achieved after ESW was 4.3 months. There was no complication except mild
      subcutaneous hemorrhage that disappeared within a week. We conclude that ESW is a
      safe and effective procedure for the treatment of delayed union of the fracture.

PMID- 19398842
TI  - Hemodynamic and echocardiographic evaluation of orthotopic heart transplantation
      with the modified bicaval anastomosis technique.
AB  - BACKGROUND: The purpose of this study was to evaluate the hemodynamic and
      echocardiographic function of hearts transplanted with the modified bicaval
      anastomosis technique (mBCAT). METHODS AND RESULTS: Twenty consecutive patients
      (14 males, 6 females, age range 14-61 [41.3 +/-11.5 years]) were evaluated 3.4 +/
      2.2 years after heart transplantation using the mBCAT. All patients were in
      status I on the waiting list, and 18 (90%) had had a left ventricular assist
      device. The donor age was 39 +/-12 years. Triple immunosuppressive regimen and
      cardiac biopsy were routinely performed. There was no hospital mortality. One
      death occurred 4.2 years after the operation because of bone marrow dysplasia and
      infection. The 8-year survival was 89% (95% confidence interval: 0.43-0.98). All
      the hemodynamic variables returned to the normal range. Low right atrial pressure
      (3.2 +/-1.5 mmHg) and low pulmonary wedge pressure (6.7 +/-2.1 mmHg) were
      associated with an excellent cardiac index (3.9 +/-0.7 L . min(-1) . m(-2)).
      Echocardiography revealed an excellent late peak velocity (52 +/-19 cm/s) and an
      E/A ratio (1.4 +/-0.6) of tricuspid flow. The grade (0-4) of tricuspid
      regurgitation averaged 1.5 +/-0.8. CONCLUSIONS: Hemodynamic and echocardiographic
      results for mBCAT were excellent. The 8-year survival was 89% with all surviving
      patients in New York Heart Association class I. The mBCAT is easy to perform and
      further facilitates cardiac transplantation.

PMID- 19398843
TI  - Left ventricular torsion in patients with secundum atrial septal defect.
AB  - BACKGROUND: Recently, assessment of left ventricular (LV) torsional deformation
      has become an important approach for quantifying LV function. This study sought
      to evaluate LV torsion using speckle tracking imaging in patients with atrial
      septal defect (ASD). METHODS AND RESULTS: Basal and apical LV short-axis images
      were analyzed in 45 asymptomatic adults with isolated secundum ASD and 45 matched
      normal subjects. The apical rotation parameters were similar between 2 groups;
      however, the peak basal clockwise rotation was significantly depressed (-5.4 +/
      2.8 degrees vs -6.9 +/-2.6 degrees , P<0.001) and time to the peak was
      significantly delayed (118.3 +/-18.8% vs 96.1 +/-12.6% of systolic period,
      P<0.001) in patients with ASD. The peak basal initial counterclockwise rotation
      in the ASD group was significantly higher (5.1 +/-3.3 degrees vs 1.8 +/-1.4
      degrees , P<0.001) and longer (75.4 +/-26.7% vs 42.5 +/-24.4% of systolic period,
      P<0.001) than that in the control group. LV peak twist was also reduced
      significantly in patients with ASD (11.9 +/-5.9 degrees vs 14.6 +/-3.5 degrees ,
      P<0.05) in comparison with the controls. CONCLUSIONS: LV systolic twist was
      significantly reduced in patients with ASD mainly because of the heterogeneous
      basal rotation.

PMID- 19398844
TI  - Diabetes mellitus as a predictor of retinopathy associated with acute myocardial
      infarction.
AB  - BACKGROUND: A unique transient retinopathy characterized by soft exudates around
      the optic disc after percutaneous coronary intervention (PCI) for acute
      myocardial infarction (AMI) has been reported, so in the present study the risk
      factors for retinopathy associated with AMI (RAMI) were investigated. METHODS AND
      RESULTS: The study group comprised 62 patients with their first AMI who underwent
      successful PCI within 24 h of onset (48 men, 14 women; age 63 +/-10 years). The
      fundus of each eye was assessed on days 3-5, and again at 4 weeks after AMI
      onset. New soft exudates developed in 29 patients (47%) at 4 weeks. The frequency
      of diabetes mellitus (DM), and the hemoglobin A(1c) and peak creatine kinase
      concentrations were higher in patients with than in those without RAMI (55% vs
      21%, P=0.008; 7.0 +/-2.0% vs 5.9 +/-1.4%, P=0.013; and 3,428 +/-2,210 IU/L vs
      2,352 +/-1,652 IU/L, P=0.036, respectively). Multivariate analysis identified DM
      as an independent predictive factor for the occurrence of RAMI (odds ratio, 6.60;
      95% confidence interval, 1.68-25.90; P=0.007). CONCLUSIONS: DM might be a risk
      factor for RAMI.

PMID- 19398845
TI  - Improved long-term prognosis of elderly women in the era of sirolimus-eluting
      stents.
AB  - BACKGROUND: The angiographic characteristics and prognosis in elderly women in
      relation to the therapeutic impact of sirolimus-eluting stents (SES) need to be
      clarified. METHODS AND RESULTS: Quantitative coronary angiography analysis was
      performed in 1,374 patients with coronary artery disease: 670 patients were
      treated with a bare metal stent (BMS) and the remaining 704 were treated with
      SES. Patients were divided into 4 groups according to gender and age (<75 years
      M/F, > or =75 years M/F), and major adverse cardiovascular events (MACE) were
      compared among them. Women > or =75 years old tended to have 3-vessel disease
      with small vessel size and the incidence of MACE in this group was high in the
      BMS era. However, in the SES era, this prognosis improved by reducing all-cause
      death and target vessel revascularization. CONCLUSIONS: Using SES has a
      therapeutic advantage for the high-risk population of elderly women with
      angiographically unsuitable lesions for percutaneous coronary intervention.

PMID- 19398846
TI  - Modifying effect of age on the association between ambient ozone and nighttime
      primary care visits due to asthma attack.
AB  - BACKGROUND: We examined the association between short-term exposure to outdoor
      air pollution and nighttime primary care visits due to asthma attack. We also
      investigated the modifying effects of age on this association. METHODS: A case
      crossover study was conducted at a primary care clinic in metropolitan Tokyo. The
      subjects were 308 children aged 0-14 years and 95 adolescents and adults aged 15
      64 years. All subjects made visits to the clinic for an asthma attack at between
      7 PM and 12 AM. Data on hourly concentrations of particulate matter with a 50%
      cut-off aerodynamic diameter < OR =2.5 microm (PM(2.5)), ozone, and nitrogen
      dioxide (NO(2)) were obtained. A conditional logistic regression model was used
      to estimate odds ratios (ORs) of primary care visits per unit increment of each
      air pollutant. RESULTS: Among children, the ORs in warmer months per 10 ppb
      increment of the 24-hour mean concentration of ozone were 1.16 (95% confidential
      interval [CI], 1.00-1.33) adjusted for temperature, and 1.29 (95% CI, 1.08-1.55)
      adjusted for PM(2.5), NO(2), and temperature. With respect to modification of the
      association by age, the ORs for 24-hour mean concentration of ozone--after
      adjustment for PM(2.5), NO(2) and temperature in warmer months--in children aged
      0-1 years, 2-5 years, and 6-14 years were 1.06 (95% CI, 0.63-1.78), 1.37 (95% CI,
      1.05-1.71), and 1.25 (95% CI, 0.87-1.82), respectively. There was no association
      between ozone and primary care visits among adults. CONCLUSIONS: An association
      was found between ozone and nighttime primary care visits for asthma attack in
      warmer months; the association was greater among preschool children.

PMID- 19398847
TI  - Association between Interleukin-1B C-31T polymorphism and obesity in Japanese.
AB  - BACKGROUND: Recent studies have revealed a close relationship between obesity and
      polymorphism in the inflammation gene. However, the association between
      interleukin-1beta (IL-1beta) and obesity remains controversial. We therefore
      investigated the association between IL-1B C-31T polymorphism and obesity in
      Japanese. METHODS: The participants were 802 inhabitants (281 men and 521 women)
      of Japan, aged 39 to 88 years, who attended a health examination in 2003. Body
      height, weight, waist and hip circumferences, and body fat percentage were
      measured. The IL-1B C-31T polymorphism was genotyped by polymerase chain reaction
      with confronting 2-pair primers. The association between IL-1B C-31T genotypes
      and various indices of obesity was then investigated. The confounding factor
      adjusted odds ratios (OR) and 95% confidence intervals (CI) for obesity were
      calculated for each IL-1B C-31T genotype by using unconditional logistic
      regression analysis. RESULTS: Among male carriers of the CT and TT genotypes, the
      ORs for high body fat percentage were 2.58 (95% CI, 1.17-6.34) and 2.81 (1.17
      7.33), respectively, as compared to carriers of the CC genotype (P for trend =
      0.037). Among women, carriers of the TT genotype had significantly higher ORs for
      high BMI (OR, 2.13; 95% CI, 1.25-3.67) and large waist circumference (2.49; 1.37
      4.66), as compared to women with the CC genotype (P for trend = 0.005 and 0.004,
      respectively). CONCLUSIONS: The IL-1B C-31T polymorphism is associated with
      obesity in Japanese. Men and women with the TT genotype of IL-1B C-31T had a
      higher risk for obesity than those with the CC genotype.

PMID- 19398848
TI  - The association between maternal smoking during pregnancy and childhood obesity
      persists to the age of 9-10 years.
AB  - BACKGROUND: We previously reported that a number of factors related to maternal
      lifestyle during early pregnancy, including smoking, are associated with
      childhood obesity at 5 years of age. In the present study, we investigated
      whether the association with maternal smoking persisted to the age of 9-10 years.
      METHODS: The study population comprised children born between April 1, 1991 and
      March 31, 1999, and their mothers. The dependent variables--childhood overweight
      and obesity at 5 and 9-10 years of age--were defined according to internationally
      acknowledged cut-off values. Maternal smoking during early pregnancy was used as
      the independent variable. RESULTS: Mothers who completed a specifically designed
      questionnaire gave birth to a total of 1644 infants during the study period.
      Anthropometric data were collected from 1302 of these children during medical
      checkups at 9-10 years of age (follow-up rate: 79.2%). Maternal smoking during
      early pregnancy was associated with obesity in 9- to 10-year-old children
      (adjusted odds ratio, 1.91; 95% confidence interval, 1.03-3.53). However, the
      point estimates at the age of 9-10 years were considerably lower than those at
      the age of 5 years. CONCLUSIONS: Our results suggest that fetal environment,
      including exposure to maternal smoking, continues to be associated with childhood
      obesity at the age of 9-10 years.

PMID- 19398849
TI  - Amount and frequency of alcohol consumption and all-cause mortality in a Japanese
      population: the JMS Cohort Study.
AB  - BACKGROUND: Lower mortality has been reported in light-to-moderate alcohol
      drinkers. We examined the association between the amount and frequency of alcohol
      consumption and all-cause mortality in a Japanese population. METHODS: We
      conducted a prospective cohort study among 8934 Japanese people (3444 men and
      5490 women) who completed a baseline survey between 1992 and 1995. We confirmed
      the date and cause of death by referring to death certificates. The Cox
      proportional hazards model was used to evaluate the effect of alcohol consumption
      on risk for all-cause mortality, after adjustment for potential confounding
      factors. RESULTS: We identified 637 (397 men and 240 women) deaths during the
      12.0 years of mean follow-up. Among men, as compared with non-drinkers, the
      relative risk was higher in ex-drinkers (hazard ratio [HR], 1.18), lower in light
      drinkers (HR, 0.95) and moderate drinkers (HR, 0.91), and significantly higher in
      heavy drinkers (HR, 1.67; 95% confidence interval, 1.10-2.55). Among women,
      light, moderate, and heavy drinkers were grouped into current drinkers. The
      relative risk was slightly higher in current drinkers (HR, 1.23), and that in ex
      drinkers was near 1.0 (HR, 0.97). In stratified analysis, the harmful effects of
      heavy drinking were more severe among male smokers and younger men. In terms of
      frequency, men who drank only on special occasions had the highest mortality (HR,
      1.28), regardless of alcohol intake per drinking session. CONCLUSIONS: In men, a
      near J-shaped association was identified between alcohol consumption and all
      cause mortality. Both the amount and frequency of alcohol consumption were
      related to mortality.

PMID- 19398850
TI  - Birth weight among singletons born to foreign-born mothers in Taiwan: a
      population-based birth register study.
AB  - BACKGROUND: We compared the birth weight of newborns born to foreign-born mothers
      (FBMs) and Taiwan-born mothers (TBMs), using data from the 2005-2006 Taiwan Birth
      Registry of singleton live births. METHODS: The Wilcox-Russell method, data
      restriction, and multiple linear regression were used to analyze the data. The
      rates of low birth weight (<2500 g) with 95% confidence intervals were computed
      for TBMs, and for each of the nationalities of FBMs. RESULTS: The mean birth
      weight of newborns of FBMs was 3157 g, which was higher than that of newborns of
      TBMs (3109 g). On analysis using the Wilcox-Russell method, both the rate and
      residual proportion of low-birth-weight (LBW) births were lower among newborns of
      FBMs (4.1% and 1.1%, respectively) than among newborns of TBMs (5.9% and 1.7%,
      respectively). After adjusting for sex, mode of delivery, maternal age, smoking
      status, predisposing maternal risk factors, and condition during pregnancy, the
      newborns of FBMs weighed 72.9 g (95% CI, 68.8 g to 77.0 g) more than the newborns
      of TBMs. When data were restricted to mothers without any adverse conditions and
      adjusted for maternal age, the differences in birth weight between the 2 groups
      remained unchanged. The rates of LBW deliveries among FBMs in Taiwan were
      significantly lower than those in their respective countries of origin.
      CONCLUSIONS: In Taiwan, newborns of FBMs had a higher birth weight than those of
      TBMs, even after accounting for potential confounding factors, and had lower
      rates of LBW deliveries than did mothers in their respective countries of origin.

PMID- 19398851
TI  - Environmental risk factors for congenital heart disease in the Shandong
      Peninsula, China: a hospital-based case-control study.
AB  - BACKGROUND: In China, and in Shandong province, the proportionate contribution of
      birth defects to infant mortality has increased, and congenital heart disease
      (CHD) is now the most common cause of birth defects. The cause of approximately
      90% of cases of congenital heart disease is multifactorial. Little is known about
      modifiable environmental risk factors or regional differences. We investigated
      putative environmental risk factors for congenital heart disease in the Shandong
      province of China in order to improve prevention of CHD. METHODS: We conducted a
      hospital-based 1:2 matched case-control study of 164 patients with congenital
      heart diseases and 328 controls, all of whom were retrospectively interviewed.
      Univariate and multivariate analyses were conducted to identify environmental
      risk factors for CHD. RESULTS: The environmental risk factors associated with CHD
      were mother's education level (odds ratio [OR], 0.31; 95% confidence interval
      [CI], 0.15-0.67), neonatal asphyxia or hypoxia (OR, 3.74; 95% CI, 1.25-11.18),
      number of previous pregnancies (OR, 2.68; 95% CI, 1.44-4.97), maternal upper
      respiratory tract infection (OR, 4.12; 95% CI, 1.56-10.85), maternal infection
      (OR, 7.98; 95% CI, 2.14-29.72), maternal B-mode ultrasound examination (OR, 4.05;
      95% CI, 1.48-11.08), and maternal mental stress (OR, 3.93; 95% CI, 1.94-7.94)
      during early pregnancy. No significant interactions were observed among these
      factors. CONCLUSIONS: Augmenting maternal mental healthcare, obtaining regular
      health counseling and testing during pregnancy, preventing upper respiratory
      tract infections, limiting medication during early pregnancy, offering health
      promotion and health education to women of childbearing age (especially those
      with less formal education), and improving obstetric procedures and techniques
      may lower the occurrence of congenital heart disease.

PMID- 19398852
TI  - Risk factors for gallstone disease in a Thai population.
AB  - BACKGROUND: Gallstone disease (GSD) is a major public health problem that is
      associated with a number of risk factors. METHODS: We conducted a case-control
      study of 407 participants comprising 207 cases with GSD and 200 controls without
      GSD, as confirmed by ultrasonography. The participants completed a questionnaire
      and underwent physical and ultrasonographic examination. The risk factors
      examined were age, sex, BMI, use of oral contraceptives, diabetes mellitus,
      cirrhosis, thalassemia, dyspepsia, family history of gallstone disease, smoking
      status, alcohol consumption, and dietary history. RESULTS: BMI, fat content of
      dietary meat, and smoking were associated with GSD. When compared to participants
      with a BMI below 25, participants with a BMI of 25 or higher had a multivariate
      relative risk of 4.1 (95% CI, 2.5-6.7). Participants who consumed meat with
      moderate fat content or high fat content had respective relative risks of 2.5 and
      2.9 (95% CI, 1.5-4.2 and 1.5-5.6), when compared to those who consumed meat with
      a low fat content. Also, the multivariate relative risk for former smokers, as
      compared to never smokers, was 2.4 (95% CI, 1.1-5.2). CONCLUSIONS: High BMI,
      consumption of high-fat meat, and smoking were associated with gallstone disease.

PMID- 19398853
TI  - Differential effects of irradiation with carbon ions and x-rays on macrophage
      function.
AB  - Macrophages are potent elicitors of inflammatory reactions that can play both
      positive and negative roles in radiotherapy. While several studies have
      investigated the effects of X-rays or gamma-rays on macrophages, virtually no
      work has been done on the responses of these cells to irradiation with carbon
      ions. Investigations into the effects of carbon ion irradiation are of particular
      interest in light of the fact that this type of radiation is being used
      increasingly for cancer therapy. In the present investigation we compared the
      effects of 250 kV X-rays with those of 9.8 MeV/u carbon ions on RAW 264.7
      macrophages over a wide range of radiation doses. Macrophage functions including
      vitality, phagocytic activity, production of the proinflammatory cytokines IL
      1beta and TNFalpha and production of nitric oxide (NO) were measured. In
      comparison to lymphocytes and fibroblasts, macrophages showed only a small
      decrease in vitality after irradiation with either X-rays or carbon ions.
      Proinflammatory cytokines and NO were induced in macrophages by LPS but not by
      irradiation alone. X-rays or carbon ions had little modulating effect on LPS
      induced TNFalpha production. However, LPS-induced NO increased in a dose
      dependent manner up to 6-fold after carbon ion irradiation, while X-ray
      irradiation did not have this effect. Carbon ion irradiation mediated a
      concomitant decrease in IL-1beta production. Carbon ions also had a greater
      effect than X-rays in enhancing the phagocytic activity of macrophages. These
      results underscore the greater potential of carbon ion irradiation with regard to
      radiobiological effectiveness.

PMID- 19398854
TI  - Microarray analysis of differentially expressed genes in the kidneys and testes
      of mice after long-term irradiation with low-dose-rate gamma-rays.
AB  - Measuring global gene expression using cDNA or oligonucleotide microarrays is an
      effective approach to understanding the complex mechanisms of the effects of
      radiation. However, few studies have been carried out that investigate gene
      expression in vivo after prolonged exposure to low-dose-rate radiation. In this
      study, C57BL/6J mice were continuously irradiated with gamma-rays for 485 days at
      dose-rates of 0.032-13 microGy/min. Gene expression profiles in the kidney and
      testis from irradiated and unirradiated mice were analyzed, and differentially
      expressed genes were identified. A combination of pathway analysis and
      hierarchical clustering of differentially expressed genes revealed that
      expression of genes involved in mitochondrial oxidative phosphorylation was
      elevated in the kidney after irradiation at the dose-rates of 0.65 microGy/min
      and 13 microGy/min. Expression of cell cycle-associated genes was not profoundly
      modulated in the kidney, in contrast to the response to acute irradiation,
      suggesting a threshold in the dose-rate for modulation of the expression of cell
      cycle-related genes in vivo following exposure to radiation. We demonstrated that
      changes to the gene expression profile in the testis were largely different from
      those in the kidney. The Gene Ontology categories "DNA metabolism", "response to
      DNA damage" and "DNA replication" overlapped significantly with the clusters of
      genes whose expression decreased with an increase in the dose-rate to the testis.
      These observations provide a fundamental insight into the organ-specific
      responses to low-dose-rate radiation.

PMID- 19398855
TI  - Introduction of a normal human chromosome 8 corrects abnormal phenotypes of
      Werner syndrome cells immortalized by expressing an hTERT gene.
AB  - Werner syndrome (WS) is an autosomal recessive disease characterized by premature
      aging and caused by mutations of the WRN gene mapped at 8p12. To examine
      functional complementation of WS phenotypes, we introduced a normal human
      chromosome 8 into a strain of WS fibroblasts (WS3RGB) immortalized by expressing
      a human telomerase reverse transcriptase subunit (hTERT) gene. Here, we
      demonstrate that the abnormal WS phenotypes including cellular sensitivities to 4
      nitroquinoline-1-oxide (4NQO) and hydroxy urea (HU), and chromosomal
      radiosensitivity at G(2) phase are corrected by expression of the WRN gene
      mediated by introducing a chromosome 8. This indicates that those multiple
      abnormal WS phenotypes are derived from a primary, but not secondary, defect in
      the WRN gene.

PMID- 19398856
TI  - Initial clinical experience of vasodilatory effect of intra-cisternal infusion of
      magnesium sulfate for the treatment of cerebral vasospasm after aneurysmal
      subarachnoid hemorrhage.
AB  - The vasodilatory effect of intra-cisternal infusion of magnesium sulfate solution
      was evaluated in 10 patients with symptomatic vasospasm after aneurysmal
      subarachnoid hemorrhage (SAH) who underwent early clipping surgery. Cisternal
      drainage was installed in the prepontine and/or sylvian fissures. Carotid
      angiography was performed immediately after the onset of symptomatic vasospasm,
      then intra-cisternal infusion of 15 mmol/l magnesium sulfate in Ringer solution
      was started at 20 ml/hr and continued until day 14. Irrigation was performed from
      the cisternal tube (inlet) to the spinal drainage (outlet). The cerebrospinal
      fluid magnesium ion concentration (1.2 +/- 0.2 mEq/l) significantly increased
      after the infusion therapy (6.0 +/- 1.7 mEq/l, p < 0.001). Repeat angiography
      showed vasodilatory effect on the spastic cerebral arteries at 3 hours after the
      infusion, especially in the arteries near to the site of cisternal drainage
      placement. The magnesium infusion also caused decreased mean arterial blood
      velocity in the spastic arteries in 6 of the 7 measured patients (162 +/- 38
      cm/sec to 114 +/- 42 cm/sec, p < 0.001). Finally, 5 of the 10 patients achieved
      good recovery, 1 patient had moderate disability, 1 patient became severely
      disabled due to meningitis, and 3 patients were vegetative or dead, due to
      failure of magnesium irrigation in 1 patient and advanced age in the other 2
      (more than 80 years old). This preliminary study indicates that intra-cisternal
      infusion of magnesium sulfate solution has vasodilatory effect on the spastic
      cerebral arteries after aneurysmal SAH.

PMID- 19398857
TI  - Brain tumor stem cells from an adenoid glioblastoma multiforme.
AB  - Brain tumors may arise from and contain cancer stem cells (CSCs) capable of self
      renewal, proliferation, and differentiation that recapitulate the parent tumor.
      These CSCs are thought to be important in gliomagenesis. Detection of CSCs
      invading the adjacent brain regions is important for the diagnosis and effective
      treatment of glioblastoma multiforme (GBM). A 57-year-old man presented with an
      adenoid GBM, and underwent resection of the tumor. Multipotent, self-renewing
      cells derived from the human adenoid GBM were isolated and identified with the
      tumor-derived stem cell surface antigen CD133 from whole autopsied patient's
      brain. Tumorsphere culture and flow cytometric analysis revealed that 1.02-2.32%
      of the cells were positive for CD133. Transplantation of cultured tumorspheres
      into the mice brain resulted in the formation of well-defined tumor masses after
      12 weeks. The histological and immunohistochemical characteristics of the
      xenograft were identical to those of the parent tumor. Examination of the
      patient's brain at autopsy showed CD133-positive cells were identified in the
      brain regions adjacent to the tumor, suggesting that CD133-positive CSCs might be
      localized to the vascular niche. Methods to localize CSCs may open new approaches
      for the treatment of brain tumors.

PMID- 19398858
TI  - Bilateral acute subdural hematomas with intracerebral hemorrhage without
      subarachnoid hemorrhage, caused by rupture of an internal carotid artery dorsal
      wall aneurysm. Case report.
AB  - A 45-year-old man presented with bilateral acute subdural hematomas (ASDHs)
      without subarachnoid hemorrhage (SAH). He was found comatose in a parked car.
      Computed tomography showed left frontal intracerebral hemorrhage (ICH) and
      bilateral ASDHs but no signs of SAH. Magnetic resonance angiography demonstrated
      an internal carotid artery dorsal wall aneurysm. Emergent surgical intervention
      was performed. However, he died of cerebral herniation 6 days later. We inferred
      that massive intracranial bleeding might have ruptured through the cortex and
      lacerated the arachnoid membrane. Aneurysm rupture generally results in
      unilateral SDH, whereas trauma is the usual cause of bilateral ASDHs with ICH.
      Our case suggests that ruptured aneurysm should be considered in patients with
      non-traumatic bilateral ASDHs without SAH.

PMID- 19398859
TI  - Intracerebral hemorrhage caused by ruptured intracavernous carotid artery
      aneurysm. Case report.
AB  - A 76-year-old woman presented with an enlarged right intracavernous carotid
      artery aneurysm first identified incidentally when she was hospitalized for
      thalamic hemorrhage. She was managed conservatively for 1 year, then suffered
      right total ophthalmoplegia associated with enlargement of the aneurysm. Two
      months later, she became comatose due to intracerebral hemorrhage in the right
      temporal lobe. Magnetic resonance imaging demonstrated further enlargement of the
      aneurysm. Emergency craniotomy found the lateral dural wall of the cavernous
      sinus was markedly expanded and torn by compression from the aneurysm. Rupture of
      the aneurysm into the intradural space through this dural defect was confirmed.
      The aneurysm was trapped after high-flow bypass, but the patient did not recover
      and died. Symptomatic enlarged intracavernous carotid artery aneurysm is
      potentially fatal and may indicate prompt surgical management.

PMID- 19398860
TI  - Photophobia as the visual manifestation of chiasmal compression by unruptured
      anterior communicating artery aneurysm. Case report.
AB  - A 37-year-old woman presented with photophobia without visual loss associated
      with chiasmal compression by an unruptured anterior communicating artery (AcomA)
      aneurysm. She had suffered progressive photophobia for one year. Neuroimaging
      indicated an AcomA aneurysm attached to the chiasm. Photophobia was resolved
      following clipping of the aneurysm. AcomA aneurysm should be considered in
      patients who experience photophobia without visual loss.

PMID- 19398861
TI  - Multiple cavernous hemangiomas of the skull associated with hepatic lesions. Case
      report.
AB  - A 55-year-old woman presented with multiple calvarial cavernous hemangiomas
      manifesting as right frontal swelling. Craniography and computed tomography
      showed an osteolytic lesion. Magnetic resonance imaging demonstrated multiple
      intraosseous lesions, and radioisotope bone scintigraphy identified even more
      numerous lesions. Total resection of the right frontal lesion and cranioplasty
      was performed. Histological examination confirmed the lesion as a cavernous
      hemangioma. Computed tomography of the abdomen revealed multiple hepatic lesions,
      which might be cavernous hemangiomas. Cavernous hemangioma is a rare bony tumor
      that should be considered in the differential diagnosis of skull tumors. A
      patient with multiple cavernous hemangiomas should undergo systemic examination
      to look for latent lesions, and regular follow-up examinations.

PMID- 19398862
TI  - Pleural malignant mesothelioma causing cord infiltration through the nerve root.
      Case report.
AB  - A 61-year-old man presented with a rare pleural malignant mesothelioma of the
      spine manifesting as progressive weakness of the bilateral lower extremities,
      numbness in the body and both legs, and dysfunction of the bladder and bowel. He
      had previous occupational exposure to asbestos while working at a car repair shop
      and had undergone right panpleuropneumonectomy under a diagnosis of sarcomatous
      type mesothelioma in the right pleural space. Magnetic resonance imaging of the
      spine with gadolinium showed an enhanced intramedullary tumor at the T4 level.
      Operative findings disclosed the clouded and swollen right posterior nerve root,
      and the pial surface was covered by clouded arachnoid-like membrane. The removed
      part of the T4 posterior nerve root and intramedullary tumor revealed malignant
      mesothelioma with invasion spreading along the posterior nerve root. He died of
      respiratory failure 3 months after the diagnosis. This case shows that spinal
      metastasis must be considered if a patient with pleural malignant mesothelioma
      shows neurological worsening and neuroimaging shows an abnormal lesion in the
      thoracic spinal cord. However, the patient's neurological condition is very
      difficult to improve in the presence of spinal cord infiltration.

PMID- 19398863
TI  - Non-traumatic atlanto-axial subluxation: Grisel's syndrome. Two case reports.
AB  - Two 8-year-old boys presented with complaints of torticollis and pain on neck
      turning. Both patients had a history of throat infection. Radiography and
      computed tomography demonstrated atlanto-axial subluxation. The patients were
      treated under diagnoses of Grisel's syndrome, unilateral or bilateral subluxation
      of the atlas on the axis associated with infection in the head or neck. Both
      patients were treated conservatively with bed rest, muscle relaxants, non-steroid
      anti-inflammatory agents, and immobilization with a soft cervical collar and
      cervical halter traction. The torticollis had resolved and reduction of atlanto
      axial subluxation was confirmed within 2 weeks in both patients. Early diagnosis
      of Grisel's syndrome with appropriate antibiotics and a cervical collar, with
      halter traction if necessary, can achieve good outcome. Surgical treatment for
      the reduction of atlanto-axial subluxation should be reserved for persistent or
      recurrent cases.

PMID- 19398864
TI  - Change of patient position using a transportation board during lumboperitoneal
      shunting. Technical note.
AB  - Lumboperitoneal shunt placement requires access to the lumbar theca in the
      lateral position, followed by subsequent laparotomy in the supine position. This
      position change and repeat draping are bothersome, especially in heavy patients,
      so we developed a method that facilitates changing the patient position while
      keeping the surgical drapes in place. An oblong plastic board covered with Teflon
      coated glassfiber cloth and surrounded by a nylon-cloth sleeve is used. The
      sleeve can be easily moved over the board, so patients can be moved in the
      transverse direction with minimal pushing force. The patient is placed in the
      lateral position on the board on the operating table and draped from the back to
      the abdomen. After catheter insertion into the lumbar theca and introduction of a
      subcutaneous tunnel to the flank, the patient is pushed in the ventral direction,
      moved to the opposite edge of the operating table, and the position is changed
      from lateral to supine, leaving the original drape intact. Finally, a catheter is
      placed by laparotomy. We were able to change position easily in 20 patients
      weighing 47-85 kg (mean 69.6 kg). This technique reduces the labor required for
      position change and preserves sterility.

PMID- 19398865
TI  - Percutaneous vertebroplasty under three-dimensional radiography guidance.
      Technical note.
AB  - An accurate, safe, and convenient method for performing percutaneous
      vertebroplasty (PVP) under three-dimensional (3D) radiography guidance has been
      developed. Six PVP procedures were performed in 5 elderly stroke patients
      complaining of back pain caused by compressive fracture which interfered with
      further rehabilitation. T(1)-weighted magnetic resonance imaging showed low
      intensity and T(2)-weighted imaging showed high intensity in the fractured
      vertebral body. The most suitable trajectory for passing the lateral mass of the
      lamina and pedicle, and reaching the vertebral body was identified on the axial
      view of 3D radiography. A 13-gauge needle was advanced appropriately in all
      patients, and improvement of back pain was obtained after injection of
      polymethylmethacrylate. No major complications occurred in any patient. PVP under
      3D radiography guidance is an accurate, safe, and convenient method.

PMID- 19398866
TI  - A mutation in the IL-2 receptor gamma chain gene associated with X-linked severe
      combined immunodeficiency accompanying opisthotonus.
AB  - Severe combined immunodeficiency (SCID) is an inherited disease with profoundly
      defective T cells, B cells, and NK cells. X-linked severe combined
      immunodeficiency (X-SCID) is its most common form. In this report, we describe a
      4-month old male with X-SCID who also showed opisthotonic posturing. Opisthotonus
      represents abnormal motor posturing and is defined as the posturing, in which the
      neck and back are arched posteriorly. The patient was referred to our hospital
      with liver dysfunction, respiratory distress, anal abscess, poor feeding and
      wasting; the patient appeared to suffer from severe and persistent infections. In
      fact, circulating T cells were not detectable, despite that the number of B cells
      was maintained in the normal ranges. Diagnosis of X-SCID was established by DNA
      analysis of the interleukin (IL)-2 receptor gamma chain gene; namely, we detected
      the novel mutation within exon 2 (221 C-->A), which leads to the substitution of
      tyrosine codon for stop codon (Y69stop). Computed tomography of the brain
      revealed mild atrophy, but no hemorrhage and no malformation. There were no
      pathological findings in the cerebrospinal fluid. Thus, the cause of opisthotonic
      posturing remains unknown. The patient died due to severe infection at the age of
      7 months. It remains to be investigated to clarify the relationship between the
      mutation and clinical manifestations. In conclusion, we have identified the novel
      mutation in the IL-2 receptor gamma chain gene, which is associated with X-SCID.
      Furthermore, this is the first report that describes the patient with X-SCID
      accompanying opisthotonus.

PMID- 19398867
TI  - Systematic lymphadenectomy improves survival in patients with advanced-stage
      primary fallopian tube cancer.
AB  - Primary fallopian tube cancer (PFTC) is a rare tumor (< 1% of all female genital
      tract cancers) and remains poorly characterized. Histologically and clinically,
      PFTC resembles epithelial ovarian cancer (EOC). The similarities in pathological
      features and patterns of spread between EOC and PFTC have led clinicians to treat
      these two malignancies in a similar manner. However, these malignancies may be
      biologically distinct and may follow different clinical courses. Lymphadenectomy
      is of crucial importance in patients with EOC, because it improves disease-free
      survival even in advanced stages. The lymph node metastasis is relatively
      frequent even in early-stage PFTC. We therefore hypothesized that lymphadenectomy
      could improve the prognosis in PFTC, as observed in EOC. The purpose of this
      study is to evaluate the prognostic role of lymphadenectomy in PFTC with a
      special focus on advanced-stage PFTC. The medical records of 18 patients treated
      in a single institute from April 1997 to August 2004 were reviewed
      retrospectively. For advanced stages (III and IV, 10 patients), mean overall
      survival for patients with positive lymph node involvement is 62.00 +/- 4.00
      months, while the patients with negative lymph node involvement were alive at
      last follow-up performed in July 2008 (log-rank; P < 0.05). Furthermore, the mean
      disease-free survival for patients with positive lymph node involvement is 46.67
      +/- 5.14 months. Based on our analysis, lymphadenectomy could improve overall
      survival and disease-free survival in patients with advanced-stage PFTC.

PMID- 19398868
TI  - Tonsillectomy with methylprednisolone pulse therapy as rescue treatment for
      steroid-resistant IgA nephropathy in children.
AB  - Primary immunoglobulin A (IgA) nephropathy is characterized by microhematuria and
      proteinuria and by the deposition of IgA in the glomerular mesangium. Steroid was
      a main drug for treatment of IgA nephropathy. However, some of children with IgA
      nephropathy are resistance to steroid treatment, but the therapy for steroid
      resistant IgA nephropathy was not established. There have been reports on the
      efficacy of tonsillectomy as an initial treatment for IgA nephropathy in adults
      and children. We examined whether tonsillectomy with methylprednisolone pulse
      therapy (tonsillectomy pulse therapy) was effective as rescue treatment for
      steroid-resistant pediatric IgA nephropathy. We studied 11 patients (age at onset
      and duration of follow-up, 11.7 +/- 2.0 and 6.2 +/- 1.1 years) who had been
      diagnosed with steroid-resistant IgA nephropathy. Clinical features, laboratory
      data, and pathological findings were retrospectively compared between before and
      after tonsillectomy pulse therapy. Urinary protein excretion was significantly
      decreased at 24.7 +/- 7.3 months after tonsillectomy pulse therapy. On renal
      pathologic examination of 6 patients who underwent renal biopsy at 17.1 +/- 6.9
      months after tonsillectomy pulse therapy, the activity index, an index of
      inflammation, was lower compared to the index evaluated before the therapy, but
      the chronic index, an index of renal sclerosis, remained unchanged. At 24.7 +/-
      7.3 months after tonsillectomy pulse therapy, seven patients had normal urine and
      four had minor urinary abnormalities; namely, none had active renal disease or
      renal insufficiency. Our findings suggest that tonsillectomy pulse therapy may be
      effective as rescue treatment for steroid-resistant IgA nephropathy in childhood.

PMID- 19398869
TI  - Factors determining cardiovascular and renal outcomes after adrenalectomy in
      patients with aldosterone-producing adrenal adenoma.
AB  - Primary aldosteronism is an important cause of secondary hypertension, because it
      is potentially curable, especially in case of unilateral aldosterone-producing
      adrenal adenoma (APA). However, the information is limited concerning the
      cardiovascular and renal outcomes in this patient population. We studied 52
      patients with APA in order to determine the pre-operative and post-operative
      factors predicting cardiovascular and renal outcomes. All 52 patients were
      hypertensive before the operation. Among 35 patients who underwent pre-operative
      electrocardiogram, 23 patients had left ventricular hypertrophy (LVH). Patients
      with LVH had lower estimated glomerular filtration rate (eGFR). Adrenalectomy
      successfully normalized or improved hypertension, hypokalemia, and aldosterone
      excess. One month after the adrenalectomy, 32 patients (62%) became normotensive,
      but 20 patients (38%) remained hypertensive. However, after an average follow-up
      period of 51 months, only 18 patients remained normotensive, while 34 patients
      were hypertensive. Thus, the rate of recurrent hypertension after adrenalectomy
      was high (14/32, 43%). Pre-operative systolic blood pressure (BP), diastolic BP,
      and post-operative plasma aldosterone concentrations were the only variables
      significantly different between the hypertensive and normotensive patients. Using
      pre-operative BP 165/110 mmHg as a cutoff has good positive predictive values (73
      92%) for post-operative long-term hypertension. Patients whose renal function
      worsened after adrenalectomy had significantly higher pre-operative plasma active
      renin levels. Thus, in patients with APA, the presence of LVH is correlated with
      impaired renal function (lower eGFR). In conclusion, pre-operative BP and post
      operative plasma aldosterone are important in predicting post-adrenalectomy
      hypertension, and a lower pre-operative plasma renin predicts the improvement in
      renal function after adrenalectomy.

PMID- 19398870
TI  - Endothelial cell apoptosis is responsible for the formation of coronary
      thrombotic atherosclerotic plaques.
AB  - Ischemic manifestations of atherosclerosis are mainly due to thrombus formation
      upon superficially eroded (denudation of luminal endothelium) plaques or deeply
      ruptured (fibrous cap rupture) plaques. Eroded plaques, atherosclerotic plaques
      without rupture, are found common in young patients of sudden death with coronary
      thrombosis. Our study aimed to investigate the role of endothelial cell (EC)
      apoptosis in eroded plaque with thrombosis using an atherosclerotic rabbit model.
      Atherosclerotic plaques were established by post-balloon-injury high-cholesterol
      feeding in 33 rabbits. After three-month feeding, a 2-cm segment of plaque-rich
      abdominal aorta for each animal was clamped in vivo and filled with
      staurosporine, which induces endothelial apoptosis, or saline for 20 minutes.
      Three days later, serum lipids and high sensitive C-reactive protein (hs-CRP), a
      valuable inflammatory parameter, were quantified, and abdominal aorta angiography
      was conducted. In addition, immunohistochemistry staining was performed for all
      processed aortae. In the staurosporine-treated aorta, endothelium integrity of
      plaques was disrupted partially or in large areas, but fibrous cap rupture was
      not observed, the findings of which were similar to eroded plaques detected in
      human subjects. As compared to saline controls, staurosporine-treated rabbits
      showed higher apoptosis scores and thrombotic scores, and more angiographic overt
      thrombosis and histological thrombosis (P < 0.01, respectively), despite the
      similar serum levels of lipids and hs-CRP. We further confirmed that apoptosis
      score was linearly associated with thrombotic score. These results suggest that
      endothelial apoptosis may be an independent risk factor for thrombosis. In
      conclusion, the increase in endothelial apoptosis is involved in the formation of
      thrombotic eroded plaques.

PMID- 19398871
TI  - D-ribose attenuates ischemia/reperfusion-induced renal injury by reducing
      neutrophil activation in rats.
AB  - The ischemia/reperfusion (I/R) represents a common pathological mechanism that
      causes renal injuries. A monosaccharide D-allose has been shown to inhibit
      neutrophil activation, which is involved in the I/R-induced organ injuries. We
      therefore examined the role of D-ribose in the I/R-induced renal injury using a
      rat model. D-ribose, a monosaccharide found in all living cells, serves as a key
      component of adenosine-5'-triphosphate and nicotinamide adenine dinucleotide.
      Male Wistar rats were divided into the sham, control and D-ribose groups. In the
      control and D-ribose groups, rats were subjected to 45 min of left renal
      ischemia, followed by 24 h of reperfusion, while the I/R procedure was not
      performed in the sham group. Rats were intravenously administered D-ribose (sham
      group and D-ribose group, 400 mg/kg) or saline (control group) 30 min before
      ischemia. Blood urea nitrogen (BUN), serum creatinine and urinary N-acetyl beta-D
      glucosaminidase (NAG) were measured as indicators of glomerular function and
      proximal tubular function. We also measured cytokine-induced neutrophil
      chemoattractant-1 (CINC-1) and myeloperoxidase concentrations to assess
      neutrophil activation and infiltration, respectively. The tissue sections were
      scored to evaluate the tubular injury. In the control group, BUN, creatinine,
      NAG, CINC-1, myeloperoxidase, histological severity score, and number of
      infiltrating neutrophils were increased following I/R insult, as compared with
      the sham group. Such increases in biochemical markers, severity score, and
      infiltrating neutrophils were significantly inhibited in the D-ribose group.
      Thus, D-ribose ameliorates the I/R-induced renal injury probably by inhibiting
      neutrophil activation, and may be useful in attenuating the renal injury
      associated with renal ischemia.

PMID- 19398872
TI  - L-type voltage-gated calcium channel is involved in the pathogenesis of acoustic
      injury in the cochlea.
AB  - Excessive calcium entry into cells leads to cell death, and voltage-gated calcium
      channels (VGCCs) are responsible for the calcium entry in the central nervous
      system. VGCC blockers inhibit excessive calcium entry and protect the central
      nervous system against various types of injury. The purpose of the present study
      was to identify the type of calcium channels that is responsible for acoustic
      injury of the cochlea. The effects of L- and T-type VGCC blockers on acoustic
      injury were examined. Female ddY mice, at 8 weeks of age, were used in this
      study. The animals were subjected to a 4-kHz pure tone of 128-dB sound pressure
      level (SPL) for 4 hours through an open field system inside a sound-exposure box.
      A L-type or T-type VGCC blocker was administered immediately before acoustic
      overexposure. The hearing ability was evaluated using the auditory brainstem
      response (ABR). ABR is an electrical signal evoked from the brainstem by the
      sound. After the final ABR measurement at two weeks after acoustic overexposure,
      cell nuclei in the organ of Corti were stained with propidium iodide, and hair
      cell loss was calculated in a region 3.66 mm from the apex. Each of four L-type
      VGCC blockers tested, i.e. diltiazem, verapamil, nicardipine and nimodipine,
      significantly improved shifts of the ABR threshold from the pre-exposure levels.
      In addition, each L-type VGCC blocker consistently decreased hair cell loss, but
      not a given T-type calcium blocker. The present findings suggest that the L-type
      VGCC is involved in the pathogenesis of acoustic injury in the cochlea.

PMID- 19398873
TI  - Accumulation of macrophages expressing myeloid-related protein 8 associated with
      the progression of sclerotic changes in children with IgA nephropathy.
AB  - Myeloid-related protein (MRP) 8 is a calcium-binding protein of the S100 family.
      The renal accumulation of macrophages expressing MRP8 is associated with the
      inflammatory activity of glomerulonephritis. We evaluated the renal accumulation
      of macrophages expressing MRP8 in children with IgA nephropathy (IgAN). We
      collected data on 25 IgAN children who had been treated with prednisolone and
      divided these patients into two groups: Favorable group, consisting of 11
      patients with normal urine and 6 with minor urinary abnormalities at 4.3 +/- 1.3
      years after initial treatment; and Unfavorable group, consisting of 8 patients
      with persistent nephropathy. The pathological renal findings were compared
      between both groups. The second biopsy was performed at two years after first
      biopsy at 5.5 +/- 4.9 months from onset. In Favorable group, the glomerular
      accumulation of macrophages expressing MRP8, and mesangial cells expressing alpha
      smooth muscle actin (alpha-SMA) were lower in the second biopsy specimens than
      those of the first biopsy specimens. In Unfavorable group, the glomerular
      accumulation of macrophages expressing MRP8 detected in the second biopsy
      specimens was similar to that of the first biopsy, while the number of mesangial
      cells expressing alpha-SMA and the index of renal sclerosis were higher in the
      second biopsy than in the first biopsy. The indexes of renal sclerosis were
      higher in children with more macrophages expressing MRP8 than in children with
      less macrophages expressing MRP8. Our results suggest that renal macrophages
      expressing MRP8 may be involved in the progression of sclerotic changes in
      children with IgAN.

PMID- 19398874
TI  - Plasma urotensin II as a marker for severity of rheumatic valve disease.
AB  - In developing countries, rheumatic valve disease (RVD) is still prevalent.
      Management of RVD depends on symptomatology, physical examination and
      echocardiographic evaluation, all of which, however, might be inadequate.
      Reliable biomarkers to establish severity of RVD and predict complications would
      be highly beneficial. Urotensin II is regarded as a cardiovascular
      autacoid/hormone, and its role in cardiovascular diseases is emerging. We
      hypothesized urotensin II might have pathophysiological roles in RVD. We
      investigated 71 patients with RVD (mean age 40 +/- 12 years, 17 female patients)
      and 25 normal subjects (mean age 40 +/- 7 years, 8 female patients). We assessed
      their New York Heart Association (NYHA) functional class, RVD severity and
      pulmonary artery pressure (PAP), and measured plasma urotensin II levels. Mitral
      regurgitation (r = 0.226, p = 0.02), tricuspid regurgitation (r = 0.238, p =
      0.02), PAP (r = 0.320, p = 0.01), and NYHA class (r = 0.213, p = 0.03) correlated
      positively with urotensin II levels. There was positive correlation between
      urotensin II levels and severity of mitral regurgitation (r = 0.248, p = 0.01)
      and tricuspid regurgitation (r = 0.326, p = 0.001). In linear regression
      analysis, only PAP was predictive of urotensin II (beta = 0.3; p = 0.02). In
      conclusion, this is the first study showing that plasma urotensin II is elevated
      in chronic RVD, associated with severe mitral and tricuspid valve regurgitation.
      Furthermore, urotensin II level is correlated with NYHA functional class, and the
      increase in PAP is predictive of plasma urotensin II.

PMID- 19398875
TI  - TGF-beta inhibits vascular sprouting through TGF-beta type I receptor in the
      mouse embryonic aorta.
AB  - Organogenesis accompanies the establishment of the vascular system which begins
      with sprouting angiogenesis. Vascular endothelial growth factor (VEGF) provides
      the primary stimulation in the vascular sprouting process but the negative
      regulation of this process remains unclear. This study examined the role of the
      transforming growth factor-beta (TGF-beta) superfamily in vascular sprouting
      using a three-dimensional dorsal aorta culture system, in which the dissected
      tissue was embedded in type I collagen gel. The cultures were maintained under
      hypoxic conditions to enhance the expression of Flk-1, a receptor for VEGF,
      thereby ensuring the responsibility to VEGF. Under the culture conditions
      employed, the dorsal aorta formed many cord-like structures in response to VEGF.
      To examine the role of TGF-beta in vascular sprouting, each member of the TGF
      beta superfamily was applied to this culture system. TGF-beta1, as well as TGF
      beta2 and TGF-beta 3, inhibited capillary formation. Likewise, activin A, another
      member of TGF-beta superfamily, also abolished vascular sprouting, but bone
      morphogenetic protein 2 did not noticeably change the morphology. Both
      neutralizing anti-TGF-beta1 antibody and TGF-beta type I receptor (ALK5)
      inhibitor partially reversed the inhibitory effect of TGF-beta1. Furthermore,
      down-regulation of ALK5 with small interfering RNA rather than activin receptor
      like kinase-1 (ALK1) reversed the effect of TGF-beta1. These data suggest that
      TGF-beta superfamily may act as an inhibitor of vascular sprouting mainly through
      ALK5 signaling pathway. We propose that VEGF may antagonize the TGF-beta
      autoregulatory action to initiate vascular sprouting.

PMID- 19398876
TI  - Lack of modulation of gastric emptying by dietary nitrate in healthy volunteers.
AB  - Nitric oxide produced endogenously in vagal neurons modulates gastrointestinal
      motor activity as an important non-adrenergic and non-cholinergic
      neurotransmitter. Other than through endogenous biosynthesis, a high
      concentration of nitric oxide also occurs by chemical reactions within the
      stomach in the presence of gastric acid through the entero-salivary re
      circulation of dietary nitrate. Although dietary nitrate can be a potential
      source of nitric oxide in the human stomach, there has been no report on the
      effect of dietary nitrate on gastric motor function. The aim of this study is to
      investigate the effect of dietary nitrate on gastric emptying, one of the major
      parameters for the gastric motor function. Fifteen healthy volunteers underwent a
      placebo-controlled (310 mg sodium nitrate or placebo), double-blind, crossover
      trial. Since a sufficient amount of gastric acid is essential for dietary nitrate
      derived nitric oxide generation in the stomach, the same protocol was repeated
      after 1-week treatment with a proton pump inhibitor, rabeprazole. Gastric
      emptying was evaluated by (13)C-octanoate breath test. The sodium nitrate
      ingestion did not affect gastric emptying either prior to or during rabeprazole
      treatment, although rabeprazole treatment itself significantly delayed gastric
      emptying, being independent of the dietary nitrate load. Confirmation of the
      delayed gastric emptying with rabeprazole indicates the sensitivity of the breath
      test employed in the present study. In conclusion, despite the potential nitrogen
      source of exogenous nitric oxide, the ingestion of 310 mg sodium nitrate, which
      is equivalent to the average daily intake of Japanese adults, does not affect
      gastric emptying in healthy volunteers.

PMID- 19398877
TI  - Spontaneous pregnancy and delivery by a mother who was born via in vitro
      fertilization/embryo transfer (IVF/ET).

PMID- 19398878
TI  - Renal cell carcinoma: biological features and rationale for molecular-targeted
      therapy.
AB  - Cancer cells are characterized by indefinite proliferation, invasiveness and
      metastases. These characteristics are usually related to one another. Namely,
      cancer cells that proliferate rapidly tend to invade and metastasize. Renal cell
      carcinoma (RCC) typically does not proliferate rapidly nor does it invade the
      surrounding tissues, but it does metastasize. RCC has several peculiar
      characteristics that are not observed in other cancers: a relatively late
      recurrence, a high frequency of paraneoplastic syndrome, hypervascularity and the
      spontaneous regression of metastatic lesions after the excision of the primary
      tumor. These clinical observations suggest that cytokines or growth factors are
      important contributors to microenvironments favoring the growth of cancer cells.
      Thus, the blockade of cell-to-cell communication might have some therapeutic
      potential. Accordingly, a popular strategy for molecular-targeted therapy for RCC
      targets the vasculization of RCC induced by vascular endothelial growth factor
      (VEGF). This review highlights the biological features of RCC that are relevant
      to molecular-targeted therapy.

PMID- 19398879
TI  - Surveillance in Barrett's esophagus: a failed premise.
AB  - BACKGROUND: It is recommended that patients in whom Barrett's esophagus is
      diagnosed undergo surveillance endoscopy. However, multiple issues regarding the
      efficacy and feasibility of surveillance remain. METHODS: Quantitative techniques
      were used to examine surveillance in patients with Barrett's esophagus. A
      retrospective case-control study was performed to determine whether surveillance
      endoscopy prolonged survival in a cohort of U.S. veterans diagnosed with
      esophageal adenocarcinoma. Cost-effectiveness analysis was employed to compare
      competing strategies of management for patients with Barrett's esophagus to
      determine whether surveillance strategies using alternative biomarkers could out
      perform dysplasia based surveillance, and whether new techniques for eradicating
      Barrett's metaplasia would constitute cost-effective strategies. RESULTS:
      Surveillance did not improve long-term survival among veterans diagnosed with
      esophageal adenocarcinoma. Lead-time bias has confounded previous reports
      claiming the efficacy of endoscopic surveillance. Cost-effectiveness analysis
      revealed that while screening 50-year old Caucasian males with heartburn may be
      cost-effective, surveillance even at 5 year intervals among patients with
      Barrett's esophagus without dysplasia exceeded the threshold of cost-effective
      care. If a biomarker were developed whose sensitivity and specificity to predict
      cancer development exceeded 80%, this could represent a more viable strategy than
      dysplasia-based surveillance and overcome the inherent inter- and intra-observer
      variations in dysplasia diagnosis that currently limit the effectiveness of
      surveillance programs. Finally, techniques that reduce cancer incidence such as
      endoscopic mucosal resection or ablation will likely be more cost-effective than
      current surveillance strategies that rely on early detection of cancer.
      CONCLUSIONS: Current recommendations for the management of patients with
      Barrett's esophagus are flawed. Future guidelines should include alternative
      markers of cancer risk and focus on strategies that reduce cancer incidence
      instead of cancer detection.

PMID- 19398880
TI  - Asymptomatically elevated blood pressure in the emergency department: a finding
      deserving of attention by emergency physicians?
AB  - The Emergency Department (ED) may be an ideal place to screen and refer patients
      for blood pressure monitoring in the outpatient setting. Yet, little is known
      about the public health significance of asymptomatically elevated blood pressure
      measurements in the ED and what to tell patients when these abnormal vital signs
      are recorded. Since the prevalence of hypertension and inadequately treated
      hypertension is so high, the incidental finding of elevated blood pressure in a
      previously undiagnosed patient may be a pivotal moment in that patient's life.
      For those patients carrying the diagnosis of hypertension, it is the author's
      opinion that the observation of elevated blood pressures should trigger advice to
      see their physicians to consider medication adjustments or changes. Emergency
      Physicians and their staff are in a unique position to screen and refer large
      populations of patients to their community physicians and help abort the long
      term sequelae of unidentified or inadequately managed hypertension. How best to
      advise physicians and their patients requires research and innovative methods for
      transmitting important information to patients that may be unrelated to their
      primary complaint in the ED.

PMID- 19398881
TI  - Local intraoral autologous bone harvesting for dental implant treatment:
      alternative sources and criteria of choice.
AB  - Dental implants are established alternatives for replacing missing teeth. In case
      of alveolar bone resorption, implant placement may be prevented unless the volume
      of hard tissues is increased before or during implantation. Autologous bone graft
      is still regarded as the "gold standard" in alveolar reconstruction., but many
      factors may influence the final outcome. The success of intraoral bone grafts, in
      fact, depends, among other factors, on the choice of donor graft material as well
      as on how the material is handled. The evidence supporting the use of autogenous
      intramembranous bone with or without the use of barrier membranes is briefly
      reviewed. The rational of donor site choice is also presented. Advantages and
      disadvantages of different harvesting site are discussed.

PMID- 19398882
TI  - New perspective in osteoarthritis: the OPG and RANKL system as a potential
      therapeutic target?
AB  - Bone remodelling is tightly regulated by a molecular triad composed of
      OPG/RANK/RANKL. The receptor activator of NF-kappaB ligand (RANKL) (localized on
      osteoblasts) enhances osteoclastogenesis via interaction with its receptor RANK
      (localized on osteoclasts), whereas osteoprotegerin (OPG) (produced by
      osteoblasts) inhibits this osteoclastogenesis by binding to RANKL. The
      equilibrium between OPG and RANKL plays a crucial role in the pathophysiology of
      bone. Although some studies have shown the efficacy of OPG as a therapeutic agent
      against bone resorption, its bioavailability and mechanism of action after
      binding to RANKL have only recently been studied. A mechanistic investigation
      based on what becomes of OPG after binding to cells expressing membranous RANKL
      demonstrated an internalization process of OPG through the clathrin pathway prior
      to proteasomal and/or lysosomal degradation. Interestingly, the OPG
      internalization process reduced the half-life of RANKL. Recent evidence has shown
      that subchondral bone alterations in osteoarthritis (OA) are intimately involved
      in cartilage degradation, and that OPG/RANKL may be implicated. Data show that
      human OA subchondral bone osteoblasts have abnormal OPG and RANKL levels and
      consequently an altered OPG and RANKL ratio. Further data also reveal the
      involvement of some osteotropic factors in these altered levels and that some of
      these factors generally target RANKL with a differential modulation of the RANKL
      isoforms. Altogether, data suggest that this system could be targeted as a new
      strategy for the treatment of OA.

PMID- 19398883
TI  - Radiosurgical treatment planning for intracranial AVM based on images generated
      by principal component analysis--a simulation study.
AB  - BACKGROUND: One of the most important factors in stereotactic radiosurgery (SRS)
      for intracranial arteriovenous malformation (AVM) is to determine accurate target
      delineation of the nidus. However, since intracranial AVMs are complicated in
      structure, it is often difficult to clearly determine the target delineation.
      PURPOSE: To investigate the usefulness of principal component analysis (PCA) on
      intra-arterial contrast enhanced dynamic CT (IADCT) images as a tool for
      delineating accurate target volumes for stereotactic radiosurgery of AVMs.
      MATERIALS AND METHODS: IADCT and intravenous contrast-enhanced CT (IVCT) were
      used to examine 4 randomly selected cases of AVM. PCA images were generated from
      the IADCT data. The first component images were considered feeding artery
      predominant, the second component images were considered draining vein
      predominant, and the third component images were considered background. Target
      delineations were first carried out from IVCT, and then again while referring to
      the first and second components of the PCA images. Dose calculation simulations
      for radiosurgical treatment plans with IVCT and PCA images were performed. Dose
      volume histograms of the vein areas as well as the target volumes were compared.
      RESULTS: In all cases, the calculated target volumes based on IVCT images were
      larger than those based on PCA images, and the irradiation doses for the vein
      areas were reduced. CONCLUSION: In this study, we simulated radiosurgical
      treatment planning for intracranial AVM based on PCA images. By using PCA images,
      the irradiation doses for the vein areas were substantially reduced.

PMID- 19398884
TI  - Radiographic abnormalities of the inferior pole of the patella in juvenile
      athletes.
AB  - We examined radiographs of the inferior pole of the patella in seven juvenile
      athletes diagnosed as having Sinding-Larsen-Johansson disease (SLJD) and
      discussed the etiology of the syndrome. Eight knees had tenderness at the
      inferior pole of the patella accompanied by radiographic abnormalities. A regular
      or irregular calcification was found at the inferior pole of the patella in three
      knees; coalescence of the calcification was found in two knees; incorporation of
      the calcification into the patella to yield a normal radiographic configuration
      of the area was found in two knees; and a small calcification separated from the
      patella was found in one knee. All of these findings varied and did not always
      correspond to the radiographic stages of the disease process identified by
      Medlar. One case was not clearly distinguished from either osteochondritis or
      stress fracture, and one case had a similar symptom to tendinitis. Thus, the
      etiology of the syndrome seems not to be unified, and the differential diagnosis
      between SLJD and osteochondritis, stress fracture, or tendinitis was difficult to
      arrive at. We were only able to conclude that the radiographic abnormalities and
      consequently the etiology of the syndrome vary, and therefore there is a
      limitation to call the syndrome accompanied by abnormal findings of the inferior
      pole of the patella under the umbrella term of SLJD.

PMID- 19398885
TI  - Retinopathy: an overlooked adverse effect of interferon-beta treatment of
      multiple sclerosis.
AB  - Interferon (IFN), which is an established maintaining therapy for multiple
      sclerosis (MS), has been reported various adverse effects. This paper describes a
      case of IFN-associated retinopathy, representing an overlooked adverse effect in
      MS. A 46-year-old woman with diabetes mellitus was diagnosed with MS and treated
      with IFNbeta-1b for three years. She displayed sudden defect of the visual field
      and ocular fundi showed retinal cotton wool spots indicating IFN-retinopathy,
      which resolved rapidly after IFN was discontinued. To evaluate the prevalence of
      retinopathy in MS, we performed fundoscopic examination on twenty MS patients
      treated with IFNbeta-1b in our hospital. However, none of the patients displayed
      retinopathy. Only four other cases of IFN- retinopathy in MS have been reported
      in the literature. Therefore, IFN-retinopathy may be uncommon in MS, but
      neurologist should be mindful of this adverse effect and regularly check the
      fundus, particularly in patients with possible risk factor, diabetes mellitus.

PMID- 19398886
TI  - Autophagy:   not good OR bad, but good AND bad.
AB  - Autophagy is a well-established mechanism to degrade intracellular components and
      provide a nutrient source to promote survival of cells in metabolic distress.
      Such stress can be caused by a lack of available nutrients or by insufficient
      rates of nutrient uptake. Indeed, growth factor deprivation leads to
      internalization and degradation of nutrient transporters, leaving cells with
      limited means to access extracellular nutrients even when plentiful.This loss of
      growth factor signaling and extracellular nutrients ultimately leads to
      apoptosis, but also activates autophagy, which may degrade intracellular
      components and provide fuel for mitochondrial bioenergetics. The precise
      metabolic role of autophagy and how it intersects with the apoptotic pathways in
      growth factor withdrawal, however, has been uncertain. Our recent findings
      ingrowth factor-deprived hematopoietic cells show that autophagy can
      simultaneously contribute to cell metabolism and initiate a pathway to sensitize
      cells to apoptotic death. This pathway may promote tissue homeostasis by ensuring
      that only cells with high resistance to apoptosis may utilize autophagy as a
      survival mechanism when growth factors are limiting and nutrient uptake
      decreases.

PMID- 19398888
TI  - A human bone NOD/SCID mouse model to distinguish metastatic potential in primary
      breast cancers.
AB  - In this study, we created a clinically relevant model using NOD/SCID mice
      engrafted with human bone fragments in both right and left flanks, and show that
      the human bone implants are viable and functional for more than 6 mo. To
      investigate the growth and metastatic behavior of breast cancer, human primary
      breast tumor specimens were transplanted into human bone grafts under only the
      right flanks of the human-bone NOD/SCID mice. Some of the engrafted tumors
      proliferated extensively with massive neo-vascularization and also metastasized
      to the initially tumor-free left flank bone grafts. We show for the first time
      that this mouse model can be used to distinguish between primary breast tumors
      that do or do not proliferate and metastasize to contralateral human bone
      implants that were initially tumor-free.

PMID- 19398887
TI  - Bidirectional control of the inner dynamics of focal adhesions promotes cell
      migration.
AB  - Focal adhesions (FA) are bidirectional mechanical biosensors that allow cells to
      integrate intracellular and extracellular cues. Their function is tightly
      regulated by changes in molecular composition and also by variation in the spatio
      temporal dynamics of FA components within this structure. A closely regulated
      turnover of FA proteins within FA sites allows cells to respond appropriately to
      their environment, thereby impacting on cell shape and function. FA protein
      dynamics are linked to FA maturation and rates of assembly and disassembly, and
      have a significant influence on tumor cell migration. Using the FRAP technique to
      investigate the hidden internal dynamics of FA, we identified two new regulators
      of FA dynamics and cell migration: the Mgat5/galectin-3 lattice and tyrosine
      phosphorylated caveolin-1 (pY14Cav1). In this short review we first introduce FA
      and their complex dynamic behavior. We then present the Mgat5/galectin-3 lattice
      and caveolin-1 and discuss their concerted role in FA dynamics, which defines
      previously unknown, interdependent roles in tumor cell migration. We conclude
      with a discussion of interesting unexplored avenues that might lead to a better
      understanding of the complex mechanism of FA dynamics.

PMID- 19398889
TI  - Mitophagy in the little lymphocytes: an essential role for autophagy in
      mitochondrial clearance in T lymphocytes.

PMID- 19398890
TI  - Mutation at the cargo-receptor binding site of Atg8 also affects its  general
      autophagy regulation function.
AB  - Autophagy is a highly conserved degradation pathway for intracellular
      macromolecules and organelles. Among those characterized autophagy regulators,
      the ubiquitin-like protein Atg8 is found to be a membrane modifier that both
      regulates biogenesis of transport vesicles and interacts with the cargo receptor
      Atg19 for selective autophagic transport of the vacuolar enzyme prApe1 in budding
      yeast. The role of Atg8 in the enlargement of vesicle membrane during
      autophagosome biogenesis has been well documented,but how Atg8 coordinates
      vesicle formation and sorting of selective cargo is largely unknown.
      Identification of the cargo-receptor binding site of Atg8 would provide
      information to solve this issue.Here we characterized Atg8 mutants that were
      defective in interaction with the prApe1 receptor Atg19 and found that the
      vesicle formation function of these Atg8 mutants was also compromised to
      different extents. Atg8 mutants with single-residue substitution at the Atg19
      binding site were defective in lipid conjugation and/or subcellular localization.
      Additional Atg8 mutants were found defective in autophagosome formation without
      affecting their interaction with Atg19, suggesting partially overlapping of the
      cargo-sorting site and its domains critical for autophagy control. Our
      observation paves the road for a more comprehensive understanding on how Atg8
      coordinates cargo sorting and vesicle formation in selective autophagic pathways.

PMID- 19398891
TI  - Macroautophagy of the GPR37 orphan receptor and Parkinson disease-associated
      neurodegeneration.

PMID- 19398892
TI  - NBR1 cooperates with p62 in selective autophagy of ubiquitinated targets.
AB  - Selective degradation of intracellular targets, such as misfolded proteins and
      damaged organelles, is an important homeostatic function that autophagy has
      acquired in addition to its more general role in restoring the nutrient balance
      during stress and starvation. Although the exact mechanism underlying selection
      of autophagic substrates is not known, ubiquitination is a candidate signal for
      autophagic degradation of misfolded and aggregated proteins. p62/SQSTM1 was the
      first protein shown to bind both target-associated ubiquitin (Ub) and LC3
      conjugated to the phagophore membrane, thereby effectively acting as an
      autophagic receptor for ubiquitinated targets. Importantly, p62 not only mediates
      selective degradation but also promotes aggregation of ubiquitinated proteins
      that can be harmful in some cell types. Is p62 the only autophagic receptor for
      selective autophagy? Looking for proteins that interact with ATG8 family
      proteins, we identified NBR1 (neighbor of BRCA1 gene 1) as an additional LC3- and
      Ub-binding protein. NBR1 is degraded by autophagy depending on its LC3
      interacting region (LIR) but does not strictly require p62 for this process. Like
      p62, NBR1 accumulates and aggregates when autophagy is inhibited and is a part of
      pathological inclusions. We propose that NBR1 together with p62 promotes
      autophagic degradation of ubiquitinated targets and simultaneously regulates
      their aggregation when autophagy becomes limited.

PMID- 19398893
TI  - Autophagy induced by 2-deoxy-D-glucose suppresses intracellular  multiplication
      of Legionella pneumophila in A/J mouse macrophages.
AB  - Legionella pneumophila Philadelphia-1 (Lp-1) can grow intracellularly in A/J
      mouse peritoneal macrophages (A/J Mphi). We previously reported that 2-deoxy-D
      glucose (2dG), when added in macrophage culture medium, inhibited the
      intracellular multiplication of Lp-1 in A/J Mphi. We found that 1 mM of 2dG
      causes LC3-II-conversion that reflects an induction of autophagy and that 1 and
      10 mM of 2dG induced apoptosis associated with caspase-4 activation. We therefore
      investigated whether 2dG-induced autophagy or apoptosis suppresses the
      replication ofLp-1 in 2dG-treated A/J Mphi. When the autophagy-related (Atg)gene
      Atg5 was knocked down by RNA interference, the Atg5-siRNA-transfected cells
      revealed an enhanced replication of Lp-1 in A/J Mphi compared with the non
      targetting siRNA-transfected cells. However, caspase-4 inhibitor did not affect
      the 2dG-induced inhibition of intracellular multiplication of Lp-1 in A/J Mphi.
      These findings suggested that autophagy, not apoptosis, suppressed the
      intracellular growth of Lp-1 in A/J Mphi when 1 or 10 mM of 2dG were added to the
      culture media.

PMID- 19398894
TI  - Letter from the guest editor. Angiogenesis in the central nervous system.

PMID- 19398895
TI  - Autophagy in ischemic preconditioning and hibernating myocardium.
AB  - Autophagy is a major protective mechanism and has been identified in response to
      hypoxia and more recently, myocardial ischemia, but it is not known whether it is
      involved in mediating ischemic preconditioning, the most powerful intervention
      known to protect myocardium against lethal ischemic injury. We examined autophagy
      in several models of preconditioning induced by six repetitive episodes of
      ischemia every 12 hours versus classical first or second-window preconditioning
      in swine. The results indicated that autophagy is an important mechanism
      mediating cardioprotection following repetitive episodes of coronary stenosis or
      coronary occlusion, but less for traditional first or second window
      preconditioning.

PMID- 19398896
TI  - Ubiquilins accelerate autophagosome maturation and promote cell  survival during
      nutrient starvation.
AB  - Ubiquilins (UBQLN), a family of adaptor proteins with partial homology with
      ubiquitin, are proposed to facilitate proteasomal degradation of ubiquitinated
      substrates. We now demonstrate a novel role for UBQLN in promoting autophagosome
      maturation during nutrient deprivation. Ectopic expression of UBQLN protects
      cells against starvation-induced cell death, while depletion renders cells more
      susceptible. This protective function requires the essential autophagy
      regulators, Atg5 and Atg7. The ubiquitin-associated (UBA) domain of UBQLN is
      required for its association with autophagosomes as well as for its prosurvival
      functions.Remarkably, during starvation-induced autophagy, UBQLN promotes the
      fusion of early autophagosomes with lysosomes.Overall, this work illustrates an
      important function for UBQLN in cell survival during nutrient starvation, which
      requires a newly recognized function for UBQLN in autophagosome maturation.

PMID- 19398898
TI  - Molecular mechanisms of maculopapular exanthema.
AB  - PURPOSE OF REVIEW: Maculopapular exanthema is a common cutaneous manifestation of
      many diseases produced by several agents able to activate the immune system, the
      most common of which are drugs and viruses. In spite of its high frequency,
      knowledge of the molecular mechanisms involved remains scarce. RECENT FINDINGS:
      The cytokine patterns in maculopapular exanthema have a Th1 or Th0 pattern,
      according to whether the reaction is induced by a drug or a virus, respectively.
      Additionally, the involvement of CD4 T-lymphocytes with cytotoxic capabilities
      has been shown in the former. Different chemokines and their receptors are also
      involved in skin homing, such as CCL20, CCL27, CXCL9 or CXCL10, and oxidative
      stress can help exacerbate the symptoms. SUMMARY: These findings may be very
      important for the diagnostic evaluation of these entities and for the development
      of new tools for diagnosis and treatment.

PMID- 19398899
TI  - Bibliography. Current world literature. Paediatric and neonatal infections.

PMID- 19398900
TI  - Squamous cell carcinoma of the external auditory canal: long-term clinical
      outcomes using surgery and external-beam radiotherapy.
AB  - OBJECTIVE: Squamous cell carcinoma (SCCA) of the external auditory canal (EAC) is
      often treated with a combination of surgery and radiotherapy (RT) to optimize the
      chance of achieving locoregional control. This retrospective review describes a
      27-year experience of treating these tumors at the University of Florida.
      METHODS: Thirty patients with histologically confirmed SCCA of the EAC received
      external-beam radiation (RT) alone or combined with surgical resection between
      1976 and 2003. Seven patients were treated with RT alone, 22 with postoperative
      RT, and 1with preoperative RT. Patients were grouped according to nodal status
      (N0/N1) and the Stell staging system for tumors of the EAC and middle ear. Early
      stage was defined as T1/T2 (n = 12) and advanced stage as T3 (n = 18). Median
      follow-up was 2 years (range, 0.1-19.4 years) with no patients lost to follow-up.
      RESULTS: The 5-year actuarial probabilities for local control, locoregional
      control, and cause-specific survival for patients with early stage (T1/T2) versus
      advanced-stage (T3) tumors were 74% and 55% (P = 0.27), 63% and 38% (P = 0.16),
      and 70% and 41% (P = 0.04), respectively. The regional control rate was 83% (P =
      0.6). There were 12 local recurrences and 4 neck recurrences as the first site of
      failure. One failure was successfully salvaged with surgery. Five of 23 (21%)
      patients undergoing surgery had significant complications (grade 3 or 4), whereas
      2 of 30 (7%) patients receiving RT experienced grade 3 complications. CONCLUSION:
      Patients with early stage disease achieved better local control, locoregional
      control, and cause-specific survival than those with advanced tumors. Less than
      half of the patients (13 of 30; 43%) were cured without significant
      complications, suggesting a suboptimal therapeutic ratio, using current treatment
      methods.

PMID- 19398901
TI  - Pancreatic tumor motion on a single planning 4D-CT does not correlate with
      intrafraction tumor motion during treatment.
AB  - PURPOSE: To quantify pancreas tumor motion on both a planning 4D-CT and during a
      single fraction treatment using the CyberKnife linear accelerator and Synchrony
      respiratory tracking software, and to investigate whether a single 4D-CT study is
      reliable for determining radiation treatment margins for patients with locally
      advanced pancreas cancer. METHODS AND MATERIALS: Twenty patients underwent
      fiducial placement, biphasic pancreatic protocol CT scan and 4D-CT scan in the
      treatment position while free-breathing. Patients were then treated with a single
      25 Gy fraction of stereotactic body radiotherapy. Predicted pancreas motion in
      the superior-inferior (SI), left-right (LR), and anterior-posterior (AP)
      directions was calculated from the maximum inspiration and maximum expiration 4D
      CT scan. For CyberKnife treatments, mean respiratory cycle motion and maximum
      respiratory cycle motion was determined in the SI, LR, and AP directions.
      RESULTS: The range of centroid movement based on 4D-CT in the SI, LR, and AP
      directions were 0.9 to 28.8 mm, 0.1 to 13.7 mm, and 0.2 to 7.6 mm, respectively.
      During CyberKnife treatment, in the SI direction, the mean motion of the centroid
      ranged from 0.5 to 12.7 mm. In the LR direction, the mean motion range was 0.4 to
      9.4 mm. In the AP direction, the mean motion range was 0.6 to 5.5 mm. The maximum
      range of movement (mean) during CyberKnife treatment in the SI, LR, and AP
      directions were 4.5 to 48.8 mm (mean 20.8 mm), 1.5 to 41.3 mm (mean 11.3 mm), and
      1.6 to 68.1 mm (mean 13.4 mm), respectively. Neither the maximum or mean motion
      correlated with the 4D-CT movement. CONCLUSIONS: There is substantial respiratory
      associated motion of pancreatic tumors. The 4D-CT planning scans cannot
      accurately predict the movement of pancreatic tumors during actual treatment on
      CyberKnife.

PMID- 19398902
TI  - Excellent results from high dose rate brachytherapy and external beam for
      prostate cancer are not improved by androgen deprivation.
AB  - PURPOSE: Prostate cancer patients treated with high dose rate brachytherapy and
      external beam radiation therapy were stratified by risk group for analysis to
      determine whether androgen deprivation therapy (ADT) affected outcome. METHODS:
      From 1991 through 1998, 411 patients were treated with 4 fractions of 5.5 to 6.0
      Gy high dose rate brachytherapy and a total of 36.0 to 39.6 Gy external beam
      radiation therapy (dose escalation over time). The dataset was prospective.
      Administration of ADT was not randomized, but it was the primary study variable.
      During this period, ADT was administered across all risk groups for various
      indications. It did not necessarily reflect advanced disease or large prostate
      size. There were 200 patients in the "ADT Group" (20% low, 48% intermediate, and
      32% high risk) and 211 in the "No ADT Group" (33% low, 44% intermediate, 23% high
      risk). The median follow-up was 6.4 years. Cases were grouped according to low,
      intermediate, and high risk groups to reduce the effects of unrecognized
      selection bias for or against the ADT group. The prostate specific antigen (PSA)
      nadir plus 2.0 ng/ml (nadir + 2) was used as the biochemical control end point.
      Local control, PSA progression-free survival, distant metastasis free survival,
      and cause-specific survival were compared. RESULTS: The 10 year PSA-PFS (nadir +
      2) for all 411 patients was 81%. The results stratified by risk group were: low
      92%, intermediate 87%, and high 63%. The low and intermediate risk groups were
      not statistically different from one another but they were both significantly
      better than the high risk group. ADT versus No ADT 10-year survival showed no
      significant differences for any outcome variable: PSA-PFS (83% vs. 81% ns), local
      control (97% vs. 99%), distant metastasis free survival (94% vs. 97%), and cause
      specific survival (97% vs. 97%). A subset analysis of PSA-PFS (nadir + 2)
      stratified by risk group revealed no difference between the ADT and No ADT
      groups. CONCLUSIONS: high dose rate brachytherapy and external beam radiation
      therapy resulted in high rates of local control, PSA progression-free survival,
      distant metastasis free survival, and cause-specific survival in all risk groups.
      Improved outcome from the use of androgen deprivation was not observed.

PMID- 19398903
TI  - ABT-751, a novel tubulin-binding agent, decreases tumor perfusion and disrupts
      tumor vasculature.
AB  - ABT-751 is an orally bioavailable tubulin-binding agent that is currently under
      clinical development for cancer treatment. In preclinical studies, ABT-751 showed
      antitumor activity against a broad spectrum of tumor lines including those
      resistant to conventional chemotherapies. In this study, we investigated the
      antivascular properties of ABT-751 in a rat subcutaneous tumor model using
      dynamic contrast-enhanced magnetic resonance imaging. A single dose of ABT-751
      (30 mg/kg, intravenously) induced a rapid, transient reduction in tumor
      perfusion. After 1 h, tumor perfusion decreased by 57% before recovering to near
      pretreatment levels within 6 h. In contrast, ABT-751 produced little change in
      muscle perfusion at either time point. To further elucidate mechanisms of drug
      action at the cellular level, we examined the effects of ABT-751 on endothelial
      cells using an in-vitro assay. ABT-751, at concentrations corresponding to plasma
      levels achieved in vivo, caused endothelial cell retraction and significant loss
      of microtubules within 1 h. The severity of these morphological changes was dose
      dependent but reversible within 6 h after the discontinuation of the drug. Taken
      together, these results show that ABT-751 is a tubulin-binding agent with
      antivascular properties. Microtubule disruption and morphological changes in
      vascular endothelial cells may be responsible, at least in part, for the
      dysfunction of tumor blood vessels after ABT-751 treatment.

PMID- 19398904
TI  - Chemoprevention of metaplasia initiation and carcinogenic progression to
      esophageal adenocarcinoma by resveratrol supplementation.
AB  - Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol found in the skin of
      the grape and red wine, has been found to have chemopreventitive effects in some
      carcinogenic models. The effects of resveratrol on the initiation of Barrett's
      metaplasia and the carcinogenic progression to esophageal adenocarcinoma have not
      been evaluated. The aim of this study was to evaluate the effects of resveratrol
      on the transition from reflux esophagitis to Barrett's metaplasia to dysplasia to
      esophageal adenocarcinoma in an established rat model. Male Sprague-Dawley rats
      underwent esophagoduodenal anastomosis as per institutional approved protocol.
      They were then treated twice weekly with intraperitoneal injection of 7 mg/kg of
      resveratrol or saline. Additional nonoperated rats served as controls. The rats
      in each group were assigned to 1, 3, or 5-month subgroups. The distal esophagus
      was preserved for blinded histopathological examination at the time of harvest.
      Thirty-one animals in the 5-month resveratrol group showed a decreased severity
      of esophagitis (P<0.0001), incidence of intestinal metaplasia (P = 0.3567), and
      incidence of carcinoma (P = 0.4590) as compared with both the saline and
      nonoperated control groups. In conclusion, morphological characteristics
      consistent with decreased esophagitis and incidences of metaplasia and esophageal
      adenocarcinoma were seen on histopathology in the resveratrol group. Resveratrol
      resulted in a small diminution of the carcinogenic effects and progression to
      metaplasia, and further human studies are designed to explore the potential
      anticarcinogenic mechanism.

PMID- 19398905
TI  - The long-term health effects of neonatal microbial flora.
AB  - PURPOSE OF REVIEW: Colonization of the newborn intestine is a complex process
      evolving over the first year of life. It is partly responsible for guiding
      immunologic development within the infant. Given the sharp escalation in
      immunologic diseases such as allergy and inflammatory bowel disease (IBD), this
      microbial-host interaction has become the focus of intense interest. DNA-based
      detection techniques have allowed increased identification of specific microbes
      involved in this symbiosis. RECENT FINDINGS: Epidemiologic studies have
      demonstrated a link between allergic diseases and alterations in the colonizing
      flora of infants. Concurrently, other work has demonstrated that interactions
      between gut flora and the intestinal epithelium seem to be central to the
      pathogenesis of IBD. In both allergy and IBD, certain bacteria seem to provide
      beneficial, protective effects via immune modulation. SUMMARY: There is a complex
      interaction between the bacteria within the developing gut and the immune system
      of the host. Colonization of the neonatal gut represents a critical window in
      this process. It appears clear that disruption within this flora has long-term
      health consequences as diverse as eczema, allergic rhinitis, and IBD. Guided
      establishment of specific species within the flora may reduce the incidence of
      these diseases.

PMID- 19398906
TI  - New insights into seafood allergy.
AB  - PURPOSE OF REVIEW: Seafood plays an important role in human nutrition worldwide,
      sustained by international trade of a variety of new seafood products. Increased
      production and consumption have resulted in more frequent reports of adverse
      reactions, highlighting the need for more specific diagnosis and treatment of
      seafood allergy. This review discusses recent literature in this field. RECENT
      FINDINGS: The most recent prevalence data from Asia highlight seafood as a
      significant sensitizer in up to 40% of children and 33% of adults. Furthermore,
      the demonstration of species-specific sensitization to salt-water and fresh-water
      prawns and processed prawn extract should improve diagnosis. Studies on humans
      demonstrated for the first time that biologically active fish allergens can be
      detected in serum samples as early as 10 min after ingestion. These studies
      highlight that minute amounts of ingested seafood allergens can quickly trigger
      allergic symptoms; also, inhaled airborne allergens seem to induce sensitization
      and reactions. In the past 2 years, over 10 additional seafood allergens have
      been characterized. Allergen-specific detection assays in food products are
      available for crustacean tropomyosin; however, many specific mollusk and some
      fish allergens are not readily identified. SUMMARY: Although cross-reactivity
      between crustacean and mollusks as well as mites is demonstrated, the often poor
      correlation of IgE reactivity and clinical symptoms calls for more detailed
      investigations. The recent development of hypoallergenic parvalbumin from carp
      could form the basis for safer vaccination products for treatment of fish
      allergy. Molecular characterization of more universal marker allergens for the
      three major seafood groups will improve current component-resolved clinical
      diagnosis and have a significant impact on the management of allergic patients,
      on food labeling and on future immunotherapy for seafood allergy.

PMID- 19398907
TI  - Disease outcomes as a consequence of environmental influences on the development
      of the immune system.
AB  - PURPOSE OF REVIEW: To review recent studies on disease outcomes as a consequence
      of environmental influences on the developing immune system early in life. RECENT
      FINDINGS: The increasing incidence of 'immunologically mediated disease of
      affluence', such as allergies, type I diabetes and inflammatory bowel disease
      (IBD), suggests that they are consequences of common environmental factors. No
      such factors have been identified, however, and prospective studies fail to
      support commonly given advice. Interest has, therefore, switched towards factors
      that could induce and maintain tolerance to allergens and autoantigens. A
      unifying link between Th1-dependent autoimmune disease and Th2-linked atopic
      allergy would be a disturbed immune regulation involving T regulatory cells.
      Microbial colonization of the gastrointestinal tract, linked with lifestyle, may
      be an important determinant. Several prospective, controlled studies, in which
      different strains of Lactobacillus were given to pregnant mothers and then to
      their newborn babies for 6-12 months, have shown a modest reduction of
      immunoglobulin E (IgE)-mediated eczema in infants. SUMMARY: Currently, there is
      poor support for giving any particular allergy-preventive advice. Novel potential
      strategies to enhance immune regulation and tolerance induction include
      modulation of gut microbiota, for example, by probiotics and prebiotics. Although
      the results are somewhat encouraging, they are insufficient to base general
      recommendations on, however.

PMID- 19398908
TI  - Wavefront-guided refractive surgery after multifocal lens implantation.
AB  - PURPOSE OF REVIEW: To examine whether wavefront-guided refractive surgery has a
      role in correcting ametropia after implantation of multifocal intraocular lenses
      (IOLs). RECENT FINDINGS: This review begins with an oversight of various
      multifocal IOLs to help understand how a wavefront might return from the IOL and
      be captured by an aberrometer. The accuracy of the wavefront may be compromised
      in eyes with multifocal IOLs by the fact that such lenses provide simultaneous
      vision--that is, a simultaneous projection of in-focus and out-of-focus images of
      an object on the retina--and hence returning wavefronts theoretically could be
      captured in a similar manner by an aberrometer. However, in isolated small
      series, reproducible wavefront refractions--in which the manifest refraction
      closely approximates the wavefront refraction and good results after refractive
      surgery--are attained in eyes with diffractive multifocal IOLs. SUMMARY: Small
      studies suggest that it is possible to perform wavefront-guided excimer light
      amplification by stimulated emission of radiation (LASER) to correct ametropia
      following multifocal lens implantation. Larger studies with longer follow-up are
      needed to determine whether eyes with multifocal lenses derive an added benefit
      from wavefront-guided refractive surgery over conventional surgery. These studies
      may help determine whether some IOLs are better suited for subsequent refractive
      surgery. The age of the patient may affect the outcome of refractive surgery
      after multifocal IOL implantation.

PMID- 19398909
TI  - Microkeratome complications.
AB  - PURPOSE OF REVIEW: Complications from laser in-situ keratomileusis surgery are
      extremely rare. However, most of the complications involve construction of the
      corneal flap, which is fashioned using various mechanical or femtosecond laser
      microkeratomes. Here, we review and discuss complications of microkeratome flaps.
      RECENT FINDINGS: Several large studies of microkeratome laser in-situ
      keratomileusis cases report a similar set of complications: partial or irregular
      flaps, buttonholes, and free flaps. Risk factors for these complications include
      increased age, preoperative hyperopia, and years of contact lens wear. Numerous
      animal and clinical studies have shown that the femtosecond platform produces
      flaps with greater stability with more consistent and accurate dimensions than
      the mechanical microkeratome. However, there is no significant difference in
      final visual outcome. SUMMARY: The aim of this review is to report complications
      associated with mechanical microkeratomes in the construction of laser in-situ
      keratomileusis flaps and to see whether there is a significant disadvantage
      compared with the femtosecond laser.

PMID- 19398910
TI  - Dry eye in 2008.
AB  - PURPOSE OF REVIEW: Although researchers continue to investigate the multifarious
      etiologic, anatomical, physiological, and pathological factors of dry eye,
      successful treatment remains a challenge. RECENT FINDINGS: Dry eye prevalence is
      substantial across populations and the term 'dry eye' is used to describe
      numerous causes and varied pathophysiologies. Advanced study of the physiological
      aspects of the ocular anatomy (e.g. cornea and conjunctiva, tear film, eyelids)
      allows improved understanding of the mechanisms involved in dry eye and the
      impact of different causes on these entities. Sophisticated diagnostics are being
      developed to efficiently identify dry eye. Management options include a variety
      of novel agents in the pipeline. SUMMARY: The development of improved etiological
      understanding and diagnostics for dry eye, as well as emerging therapeutics, will
      likely allow targeted therapy in the future.

PMID- 19398911
TI  - Schnyder corneal dystrophy.
AB  - PURPOSE OF REVIEW: The present review of Schnyder corneal dystrophy (SCD)
      corrects the misconceptions in the published literature about this disease.
      Understanding the clinical findings facilitates diagnosis of the dystrophy.
      RECENT FINDINGS: Retrospective case series of 115 affected individuals from 34
      SCD families identified since 1989 reports the clinical findings in a large
      cohort and the long-term visual morbidity of SCD. The configuration of the
      progressive corneal clouding is predictable on the basis of age and, contrary to
      many older publications, only 54% of affected patients were found to have corneal
      crystals. Penetrating keratoplasty was reported in 20 of 37 (54%) patients of at
      least 50 years and 10 of 13 (77%) patients of at least 70 years. Best corrected
      visual acuity 1 year prior to penetrating keratoplasty in 15 eyes (nine patients)
      ranged from 20/25 to 20/400 including seven eyes with other ocular disorders.
      Best corrected visual acuity in the remaining eight eyes was 20/25 to 20/70.
      These patients often complained of glare preoperatively, which most likely
      resulted from light scattering from the corneal cholesterol. CONCLUSION: The
      literature on SCD must be changed to reflect new information about the disease.
      When present, corneal crystals facilitate disease diagnosis but the examiner must
      be aware that they are only present 54% of the time. Although scotopic vision
      remains good until old age, disproportionate loss of photopic vision with
      frequent complaints of glare necessitates penetrating keratoplasty in the
      majority of patients over 50 years of age.

PMID- 19398912
TI  - Refractive surgery in the United States Air Force.
AB  - PURPOSE OF REVIEW: Laser refractive surgery in the United States Air Force has
      developed into a robust program since its inception in 2001. The goal of this
      study is to summarize recent developments in the program. Presentations at
      national meetings, recently published articles, and unpublished data from ongoing
      studies in the area of photorefractive keratectomy and laser-assisted in-situ
      keratomileusis are discussed. RECENT FINDINGS: Photorefractive keratectomy
      continues to be the most commonly performed corneal refractive surgery procedure
      in the United States Air Force. However, as the overall superiority of
      femtosecond laser-assisted in-situ keratomileusis flaps compared with
      microkeratome-assisted flaps continues to be established, there is an increasing
      trend towards this procedure. With a recent change in Air Force policy,
      photorefractive keratectomy and laser-assisted in-situ keratomileusis are now
      both approved for nonaviators and aviators, with the aviators undergoing contrast
      sensitivity and other additional testing to ensure readiness. SUMMARY: As members
      of the United States Air Force have stringent visual demands in carrying out
      their duties, the quality and safety of any refractive procedure are of the
      utmost importance. Thorough evaluation of ongoing advances in refractive surgery
      will help ensure that our airmen continue to meet the visual demands placed on
      them.

PMID- 19398913
TI  - Prevalence of cardiovascular risk factors in the Middle East: a systematic
      review.
AB  - The aim of this study was to determine the prevalence of key cardiovascular risk
      factors in the Middle East region. We conducted a systematic review of the
      literature through searches in the MEDLINE/PubMed and PARLINE databases between
      January 1980 and April 2005. Cohort studies published from 1980, in English,
      which included at least 1000 participants that reported the prevalence of at
      least one of the following; diabetes mellitus, obesity (body mass index > or =30
      kg/m(2)), hypertension, hyperlipidemia, and smoking in the Middle East region.
      Data were abstracted using standardized data abstraction forms. Studies were
      combined using random-effect models. In total, 51 studies (267 537 participants)
      were included. On the basis of a random-effect model, the overall prevalence of
      obesity was 24.5% [95% confidence interval (CI): 21.8-27.5; I(2): 99.3%; 24
      studies], diabetes mellitus was 10.5% (95% CI: 8.6-12.7%; I(2): 99.4%; 24
      studies), hypertension was 21.7% (95% CI: 18.7-24.9; I(2): 99.5%; 24 studies),
      smoking was 15.6% (95% CI: 12.3-19.6%; I(2): 99.7%; 21 studies). Smoking was more
      common in men than women, whereas obesity and hypertension were more common in
      women. The overall prevalence was not calculated because of marked variations in
      the definition of dyslipidemia among studies. There is a high prevalence of
      diabetes mellitus, obesity, hypertension, and smoking in the Middle East. The
      prevalence of obesity and hypertension was higher in women, whereas prevalence of
      smoking was higher in men. These data suggest that cardiovascular disease will be
      a major health problem in the Middle East.

PMID- 19398914
TI  - TNRC9/LOC643714 polymorphisms are not associated with breast cancer risk in
      Chinese women.
AB  - Variants in several genes are known to confer increased susceptibility to breast
      cancer, but the frequencies of these mutations in the population are very rare
      and different between race or ethnic groups. Genetic variation in trinucleotide
      repeat containing 9 (TNRC9) and the hypothetical gene LOC643714 (TNRC9/LOC643714)
      is a newly described risk factor for breast cancer. Here, we investigated the
      association among the three single nucleotide polymorphisms (SNPs) in
      TNRC9/LOC643714 and breast cancer risk and clinico-pathological parameters in a
      hospital-based Chinese population. Genomic DNA was extracted from peripheral
      blood lymphocytes. Polymerase chain reaction-ligation detection reaction was used
      to genotype 321 breast cancer cases and 330 controls. In addition, the
      representative polymerase chain reaction products were subjected to direct DNA
      sequencing to confirm the accuracy of this method. The odds ratios and 95%
      confidence intervals were calculated by an unconditional logistic regression
      model. There was no significant association between the risk of breast cancer and
      three SNPs of TNRC9/LOC643714 gene polymorphisms and their haplotypes. No
      significant correlation was found between the TNRC9/LOC643714 polymorphisms and
      age at diagnosis, lymph node metastases, estrogen receptor status, or
      progesterone receptor status, respectively. None of these three SNPs of
      TNRC9/LOC643714 gene is associated with individual susceptibility to breast
      cancer in Chinese women.

PMID- 19398915
TI  - An uncommon cause of headache after headbanging at a party.
AB  - Subdural haematomas can result from bridging vein rupture. Rotational
      acceleration in the sagittal plane and in a forward direction, as in falls, is
      very likely the 'mechanical' cause of subdural haematoma, as shown in cadaveric
      studies. Some recreational activities, for example roller-coaster rides and
      bungee jumping, have been associated with subdural haematoma, owing to
      acceleration/deceleration or repetitive head movements. We report a case of
      chronic subdural haemorrhage in a male teenager without precipitating factors and
      no history of head trauma. This case shows the value of good history-taking in
      medical diagnosis and that one should be aware of the risks of violent sports or
      dancing and the minimal clinical signs encountered.

PMID- 19398916
TI  - Association of collagenous colitis with prurigo nodularis.
AB  - The etiology and pathogenesis of collagenous colitis (CC) is poorly understood
      and probably multifactorial; many potential pathophysiological mechanisms have
      been described, although none have been conclusively proved. Circumstantial
      evidence suggests that CC appears as an autoimmune response to a luminal or
      epithelial antigen of unknown origin. Infections and certain drugs (e.g. NSAID,
      lansoprazole) may act as triggers for an immune-mediated process. CC is
      characterized clinically by chronic watery, nonbloody diarrhea with normal
      endoscopic appearance and without radiological abnormalities, but specific
      microscopic changes in the colon. Histopathology is featured by the presence of a
      thickened subepithelial collagen band adjacent to the basal membrane. Up to 40%
      of patients with CC have associated diseases of autoimmune or inflammatory
      origin, such as thyroid disease, coeliac disease, rheumatoid arthritis, diabetes
      mellitus, Sjogren's syndrome, CREST syndrome, scleroderma, pernicious anemia, and
      sarcoidosis. Prurigo nodularis is a chronic condition characterized by intensely
      pruritic, lichenified, or excoriated papules and nodules of unknown etiology. It
      is assumed to represent a cutaneous reaction pattern to repeated scrubbing or
      scratching caused by pruritus. We report a case of CC and prurigo nodularis. To
      our knowledge, this association has not been reported earlier.

PMID- 19398917
TI  - N-acetylcysteine prevents carbon tetrachloride-induced liver cirrhosis: role of
      liver transforming growth factor-beta and oxidative stress.
AB  - OBJECTIVES: N-acetylcysteine (NAC) is an antioxidant, a precursor of reduced
      glutathione, and an inhibitor of the profibrotic cytokine liver transforming
      growth factor-beta (TGF-beta). Carbon tetrachloride (CCl4) cirrhosis is
      characterized by oxidative stress and fibrosis. Therefore, the aim of this work
      was to study the effect of NAC on experimental cirrhosis. METHODS: CCl4 was
      chronically administered for 8 weeks along with 300 mg/kg of NAC orally once a
      day. Alkaline phosphatase, alanine aminotransferase, and gamma
      glutamyltranspeptidase were measured in plasma. Hydroxyproline, glycogen, lipid
      peroxidation, glutathione were determined in liver samples by colorimetric
      methods. TGF-beta was evaluated by western blotting, and a histopathological
      analysis was performed. RESULTS: Serum markers of liver damage increased by CCl4
      intoxication (P<0.05), whereas cotreatment with NAC prevented these increases
      (P<0.05); glycogen was depleted in the cirrhotic group (P<0.05), but preserved by
      NAC (P<0.05). Lipid peroxidation increased and glutathione decreased by the
      administration of CCl4 (P<0.05), again NAC prevented both effects (P<0.05).
      Importantly, collagen increased by about seven-fold in the CCl4 group (P<0.05);
      administration of NAC preserved the normal levels of collagen (P<0.05).
      Biochemical determinations were corroborated by hematoxylin and eosin, and
      trichromic stains. Western blots revealed a four-fold increase in TGF-beta in the
      group receiving CCl4, NAC cotreatment abolished TGF-beta signal (P<0.05).
      CONCLUSION: Our results strongly suggest that NAC prevents experimental cirrhosis
      by two mechanisms: by preventing oxidative stress and by downregulating the
      profibrogenic cytokine TGF-beta. As NAC is currently used in humans intoxicated
      with paracetamol, it can be tested in fibrotic or cirrhotic patients under
      controlled trials.

PMID- 19398918
TI  - Prevalence and treatment of hyperlipidemia in patients with chronic hepatitis C
      infection.
AB  - BACKGROUND: Patients with chronic hepatitis C (HCV) infection can also have
      hyperlipidemia. Glucose intolerance has been associated with HCV infection and
      treating hyperlipidemia in this and other high-risk groups is warranted. We
      hypothesized that hyperlipidemia is common in patients with hepatitis C and that
      it is under-treated for fear of worsening liver function. DESIGN: From the
      Stratton Veterans Affairs Medical Center computerized database, we collected
      information on patients with HCV infection enrolled in hepatology clinic. We
      collected information on age, sex, duration of HCV infection, concomitant
      diagnoses, medications they were on, laboratory values including hepatic
      function, glucose, and lipid levels. We collected information on the lipid levels
      and various cardiovascular risk factors. METHODS: This is a retrospective study
      involving record review. We analyzed the data collected from the records for
      prevalence of high cholesterol (as defined by the National Cholesterol Education
      Program) and for prevalence of various cardiovascular risk factors. We analyzed
      prevalence of treatment of hyperlipidemia in various risk groups. In the patients
      who were treated for hyperlipidemia, we collected information on any worsening
      hepatic function that led to treatment discontinuation. RESULTS: Six hundred and
      twenty-eight (70.5%) out of 891 patients with hepatitis C had hyperlipidemia. Of
      the 628 patients who had hyperlipidemia, 81 (12.7%) had positive antibody and RNA
      not tested; 162 (25.4%) had positive antibody but negative RNA testing; and 385
      (61.3%) had positive testing for viral RNA. Two hundred and eighty-four (45.2%)
      of 628 patients with hyperlipidemia were eligible for treatment to lower it. Of
      146 patients with hyperlipidemia and diabetes mellitus or arterial disease who
      were qualified for treatment (LDL >99), 95 (65.1%) were treated with lipid
      lowering medication. Of 148 patients with hyperlipidemia and without diabetes or
      arterial disease who were qualified for treatment, 64 (43.3%) were treated with
      lipid-lowering medication. CONCLUSION: A high prevalence of hyperlipidemia in
      patients infected with HCV is observed. Prevalence is highest among those who are
      positive for viral RNA. About half the patients with hyperlipidemia were eligible
      for treatment with drugs to lower it. Treatment of hyperlipidemia with medication
      though surprisingly common could improve.

PMID- 19398919
TI  - Infliximab-associated alveolitis after treatment for severe left-sided ulcerative
      colitis.
AB  - Here we describe a patient with ulcerative colitis who developed alveolitis after
      infliximab therapy. With earlier case reports of development of alveolitis in
      rheumatoid arthritis patients after infliximab infusion, the temporal
      relationship between the infliximab therapy and the development of alveolitis in
      this case, raises the possibility that the two might be causally related. With an
      increasing trend towards treating moderate to severely active ulcerative colitis
      patients with infliximab as a rescue therapy, clinicians should be aware of this
      potentially serious complication.

PMID- 19398920
TI  - Interinstrument reliability of the RT3 accelerometer.
AB  - The objective of this study was to assess the interinstrument reliability of six
      RT3 accelerometers for measuring physical activities. Each of the six healthy
      participants, mean age 36.1 years (SD 9.4), carried six RT3 accelerometers (same
      type and same producer) simultaneously placed ventrally at the waist belt. The
      participants performed three standardized activities: walking on a treadmill at
      3.0 km/h and 5.0 km/h, and sitting on a chair. Each activity lasted 5 min. The
      recordings of the accelerometers were compared with each other to assess
      interinstrument reliability. A correlation of 0.75 or higher was interpreted as
      sufficient. The mean Pearson correlation between the six accelerometers was r =
      0.78 (0.46-0.97). The intraclass correlation between the accelerometers was 0.75
      (95% confidence interval: 0.46-0.95, P <0.01). In conclusion, the interinstrument
      reliability of the RT3 accelerometer is sufficient. However, the lower limit of
      the confidence interval is low, indicating a challenge to the reliability.

PMID- 19398922
TI  - Increased detection of HIV-1 drug resistance at time of diagnosis by testing
      viral DNA with a sensitive assay.
AB  - OBJECTIVE: HIV-1 drug resistance has been detected in 8%-24% of recently infected
      North Americans when assessed by consensus sequencing of plasma. We hypothesized
      that rates were likely higher but not detected because drug-resistant mutants are
      transmitted or regressed to levels below the limit of detection by consensus
      sequencing of HIV-1 RNA. METHODS: Specimens from antiretroviral-naive individuals
      recently diagnosed with HIV-1 infection were compared at 15 codons to determine
      if testing of DNA using a sensitive oligonucleotide ligation assay (OLA) would
      detect drug resistance mutants not evident by consensus sequencing of serum.
      RESULTS: HIV-1 drug resistance at 15 major resistance codons was greater by OLA
      compared with consensus sequencing: 18 of 104 vs. 12 of 104 individuals (P < or =
      0.008) and 33 vs. 18 total mutations (P < or = 0.001); increasing the rate of
      detection at these 15 codons by 83%. Additional mutations were detected by
      consensus sequencing at L33, M46, D67, V108, and K219 that were not assessed by
      OLA. CONCLUSIONS: The increased detection of drug-resistant HIV-1 by testing
      peripheral blood cells with a sensitive assay implies that both low and high
      levels of drug-resistant mutants are transmitted or persist in antiretroviral
      naive individuals, suggesting that the clinical relevance of mutants persisting
      at both levels should be evaluated.

PMID- 19398921
TI  - A simplification trial switching from nucleoside reverse transcriptase inhibitors
      to once-daily fixed-dose abacavir/lamivudine or tenofovir/emtricitabine in HIV-1
      infected patients with virological suppression.
AB  - BACKGROUND: Data comparing abacavir/lamivudine versus tenofovir/emtricitabine in
      antiretroviral-naive patients are controversial. We compared 48-week efficacy and
      safety of these combinations as substitutes of nucleosides in patients with
      virological suppression. METHODS: We randomly assigned 333 HIV-1-infected
      patients on lamivudine-containing triple regimens with <200 copies per milliliter
      for at least 6 months to switch their nucleosides to either abacavir/lamivudine
      (n = 167) or tenofovir/emtricitabine (n = 166). The primary outcome was treatment
      failure ["switching = failure" intention to treat (ITT) analysis, noninferiority
      margin 12.5%]. Secondary outcomes were time to treatment failure, virological
      failure, adverse events, and changes in CD4 count, fasting plasma lipids,
      lipodystrophy, body fat, bone mineral density, and renal function. RESULTS:
      Treatment failure occurred in 32 patients (19%) on abacavir/lamivudine and 22
      patients (13%) on tenofovir/emtricitabine [difference 5.9%; (95% confidence
      interval -2.1% to 14.0%), P = 0.06]. Four patients in the abacavir/lamivudine
      group versus none in the tenofovir/emtricitabine group developed virological
      failure [difference 2.4; (95% confidence interval 0.05 to 6.0), P = 0.04]. Twenty
      three patients (14%) assigned to abacavir/lamivudine and 10 (6%) to
      tenofovir/lamivudine experienced grade 3 or 4 adverse effects (P = 0.03). CD4
      counts and plasma lipids showed higher increments in the abacavir/lamivudine
      group than in the tenofovir/emtricitabine group. CONCLUSIONS: In HIV-1-infected
      patients with virological suppression, abacavir/lamivudine did not meet the
      noninferiority outcome for treatment efficacy compared with
      tenofovir/emtricitabine.

PMID- 19398923
TI  - Serum leptin levels and irritable bowel syndrome: a new hypothesis.
AB  - GOALS: This study was undertaken to investigate the relationship between serum
      leptin levels and the development irritable bowel syndrome (IBS). BACKGROUND:
      Stress has been known as an important causative factor in IBS. Various studies
      have indicated the relationship between serum leptin levels and stress levels. So
      searching the relationship between the production and level of this hormone and
      development of IBS may help to understand the pathophysiology of the disease.
      STUDY: This was a case-control study. Eighty IBS patient and 80 controls were
      recruited. All participants were asked to fill in a questionnaire included
      demographic information and medical history and also a stress questionnaire.
      Serum leptin level was measured by enzyme-linked immunosorbent assay method. Chi
      square, Student t test, Pearson correlation and logistic regression were used for
      investigating the relationships between variables. RESULTS: Mean serum leptin
      levels were 7.41 and 19.33 ng/mL in IBS and control groups, respectively
      (P<0.001). Participants in IBS group had significantly higher stress levels than
      controls (P<0.001). Multivariate logistic regression analysis showed that
      adjusted odds ratios (ORs) for serum leptin level (OR: 0.9; 95% confidence
      interval: 0.85-0.94) and stress level (OR: 1.15; 95% confidence interval: 1.09
      1.23) were nearly the same as crude ones. CONCLUSIONS: This study indicated the
      relationship between leptin and IBS for the first time. Our results show that
      serum leptin level is significantly lower in IBS group than controls and this
      relationship is independent of other variables such as stress levels, body mass
      index, etc. This may help in better understanding of the pathogenesis of IBS and
      consequently lead to the development of more effective treatments.

PMID- 19398924
TI  - Increased body mass index after H. pylori eradication for duodenal ulcer
      predisposes to erosive reflux esophagitis.
AB  - BACKGROUND: A higher body mass index (BMI) may lead to a more adverse outcome of
      reflux esophagitis. The study aimed to determine whether increased BMI after H.
      pylori eradication in duodenal ulcer patients predisposes to erosive reflux
      esophagitis. METHODS: Four hundred fifty-nine patients with Helicobacter pylori
      positive duodenal ulcers but without reflux esophagitis were evaluated. Serial
      BMIs were collected before therapy and on the 2nd, 6th, and 12th months after H.
      pylori eradication. New-onset reflux esophagitis was recorded. RESULTS: In 350
      patients with complete follow-up, mean BMI increased from the second month after
      H. pylori eradication (P<0.001). H. pylori eradication also led to a net increase
      of BMI >1.5 kg/m in nearly 20% of patients in the 12-month follow-up, whereas new
      onset of reflux esophagitis was noted in 16.3% (57/350). Baseline BMI, prevalence
      rate of hiatus hernia, and net increase of BMI were higher in patients with new
      onset reflux than in those without (P<0.05). Multiple logistic regression
      confirmed higher baseline BMI, hiatus hernia, and net BMI increase >1.5 kg/m
      after H. pylori eradication were independently associated with new-onset reflux
      esophagitis (P<0.05). CONCLUSIONS: Eradication of H. pylori may lead to a
      significant net increase of BMI in patients with duodenal ulcers. Such BMI gain,
      as well as higher baseline BMI and hiatus hernia, predisposes to new-onset reflux
      esophagitis after H. pylori eradication.

PMID- 19398925
TI  - Functional dyspepsia: Validation and results of a novel survey instrument to
      evaluate patient knowledge and perceptions.
AB  - BACKGROUND: Patients' knowledge and perceptions of functional dyspepsia (FD) may
      affect illness behavior and healthcare utilization. AIMS: To develop, validate,
      and administer a survey instrument to assess symptoms, knowledge, and fears in FD
      patients. METHODS: A 66-item questionnaire was generated. Items assessed domains
      of etiology, diagnosis, natural history, and fears. Face and content validity
      were established through expert review and a patient focus group. After
      validation, questionnaires were mailed to a separate group of FD patients.
      Responses were analyzed using scales and means. RESULTS: For survey validation,
      66 of 80 patients (83%) returned both surveys. Internal consistency was good for
      most scale level measures (alpha=0.50 to 0.90). Reliability coefficients were
      good for measures of symptom assessment (intraclass correlation coefficient=0.75
      to 0.89) and consulting behaviors (intraclass correlation coefficient=0.76 to
      0.89). After survey validation, an additional 223 (62.8%) questionnaires were
      returned. Misperceptions were noted in the domains of etiology, diagnosis,
      treatment and risks of FD. Forty-eight percent of the respondents believed FD
      increases the risk of developing an ulcer and 32% believed there was an increased
      risk of developing stomach or colon cancer. CONCLUSIONS: This novel questionnaire
      demonstrated good validity and reliability in FD patients, and identified
      significant misperceptions about the etiology, evaluation, treatment, and natural
      history of FD.

PMID- 19398926
TI  - Body mass index and serum aminotransferase levels in Korean men and women.
AB  - BACKGROUND AND AIMS: Obesity has been postulated as contributing to the risk of
      nonalcoholic steatohepatitis. With the surging obesity epidemic, an ensuing
      epidemic of nonalcoholic steatohepatitis and its sequelae is of concern. The
      objectives of this clinical research study were to examine the association
      between body mass index (BMI) and serum aminotransferase levels. METHOD: A study
      was carried out on 1,166,847 Koreans (731,560 men and 435,287 women), 30 to 95
      years of age, who received health insurance from the National Health Insurance
      Corp and had a biennial medical evaluation from 1992 to 1995. RESULTS: Across the
      range of BMI values (<18.5 to >or=32 kg/m) in men, alanine aminotransferase (ALT)
      was estimated to increase by 18.8 U/L and aspartate aminotransferase (AST)
      increased by 7.1 U/L. In women, ALT increased by 9.9 U/L, whereas AST increased
      by 4.5 U/L. In men, interactions between BMI and alcohol consumption were
      significant (P<0.001) for ALT and AST, but the degree of effect modification was
      quantitatively minor. However, ALT and AST levels were somewhat higher in heavy
      alcohol drinkers than in nondrinkers. For women, the relationship of
      aminotransferase levels with BMI did not vary by alcohol consumption. The
      relationship of BMI with aminotransferase weakened with increasing age.
      CONCLUSIONS: In Korea, ALT and AST are strongly associated with BMI and increased
      progressively from the lowest to the highest strata of BMI. The association of
      BMI with aminotransferase levels was modified by age and sex.

PMID- 19398927
TI  - Comparison of reflux frequency during prolonged multichannel intraluminal
      impedance and pH monitoring on and off acid suppression therapy.
AB  - BACKGROUND: The aim of this study was to assess and compare reflux frequency
      during prolonged multichannel intraluminal impedance and pH monitoring with
      special attention to the 2-hour postprandial interval after the major meal in
      patients on or off proton pump inhibitor (PPI) therapy. MATERIALS AND METHODS: We
      retrospectively analyzed multichannel intraluminal impedance and pH studies
      performed in 110 patients monitored on (n=70) or off PPI (n=40) to assess number
      of acid and nonacid reflux episodes per hour (RE/h). RESULTS: Patients on PPI had
      significantly higher mean number of nonacid than acid RE/h during the total
      monitoring and 2-hour postprandially (pp). The mean number of nonacid RE/h was
      significantly higher during 2-hour pp than the total monitoring period (4.5 vs.
      1.7). Patients off PPI had significantly higher mean number of acid than nonacid
      RE/h only during the total monitoring. The total number of RE/h was significantly
      higher during 2-hour pp than the total monitoring (5.1 vs. 2.3). Patients on PPI
      had significantly higher mean number of nonacid RE/h whereas patients off PPI had
      significantly higher mean number of acid RE/h throughout total monitoring and 2
      hour pp. Number of RE/h was numerically (2.3 vs. 1.7) but not statistically
      greater off PPI than on PPI during total monitoring. CONCLUSIONS: The total
      number of reflux episodes increases during the postprandial period irrespective
      of PPI therapy. Maximal rate of reflux episodes occurs during the postprandial
      period and is the same whether taking PPI or not.

PMID- 19398928
TI  - Accuracy of urea breath tests tablets after 10 minutes compared with standard 30
      minutes to diagnose and monitoring Helicobacter pylori infection: a randomized
      controlled trial.

PMID- 19398929
TI  - Can the growth rate of a gallbladder polyp predict a neoplastic polyp?
AB  - GOALS: The aim of this study was to evaluate whether the growth rate of a
      gallbladder (GB) polyp is a predictive indicator for neoplastic polyps.
      BACKGROUND: Cholecystectomy for GB polyps that are larger than 10 mm is generally
      recommended because of the high probability of neoplasm. In contrast, a follow-up
      strategy is preferred for GB polyps smaller than 10 mm. However, there are no
      treatment guidelines for polyps that grow in size during the follow-up period.
      STUDY: We retrospectively investigated 145 patients with GB polyps who underwent
      at least 1 ultrasonographic follow-up examination over an interval greater than 6
      months, before cholecystectomy at Samsung medical center, South Korea, from 1994
      to 2007. The growth rate was determined based on the change in size per time
      interval between 2 ultrasonographic examinations (mm/mo). RESULTS: The median age
      of the patients was 48 years (range: 25 to 75). One hundred twenty-five non
      neoplastic polyps and 20 neoplastic polyps were found. Neoplastic polyps were
      more frequently found in patients older than 60 years, those with hypertension, a
      polyp size greater than 10 mm, and a rapid growth rate greater than 0.6 mm/mo. On
      multivariate analysis, however, the growth rate was not related to the neoplastic
      nature of a polyp, but older age (>60 y) and large size (>10 mm) were
      significantly associated with neoplastic polyps. CONCLUSIONS: Patient's age (>60
      y) and large polyp size (>10 mm) were significant predictive factors for
      neoplastic GB polyps. GB polyps less than 10 mm in diameter do not require
      surgical intervention simply because they grow.

PMID- 19398930
TI  - Effects of probiotics for the prevention and treatment of radiation-induced
      diarrhea.
AB  - BACKGROUND AND AIMS: Probiotic supplementation seems to provide beneficial
      effects in the prevention and treatment of radiation-induced diarrhea. We
      performed a systematic review and meta-analysis to estimate the efficacy of
      probiotic supplementation for prevention and treatment of radiation-induced
      diarrhea. METHODS: Two reviewers independently searched PubMed, EMBASE, Cochrane
      Library, Google Scholar and on-line clinical trials registers (up to January
      2009) for randomized controlled trials that evaluated the efficacy of probiotic
      supplementation for the prevention and treatment of radiation-induced diarrhea.
      Each clinical trial was separately evaluated for study characteristics,
      methodologic quality and outcomes. Results of the randomized controlled trials
      were pooled in a meta-analysis. RESULTS: Four randomized controlled trials were
      included. Three clinical trials, with a total of 632 subjects, evaluated the
      preventive effects of probiotic supplementation and 1 study evaluated the
      therapeutic role. Random effects meta-analysis of the preventive trials did not
      show significant differences between probiotic supplementation and control groups
      (odds ratio 0.47; 95% confidence interval: 0.13-1.67). However, the few available
      trials and the presence of significant clinical and statistical heterogeneity
      limited the analysis. Similarly, the therapeutic clinical trial did not show
      significant differences between active and placebo groups. No major adverse
      events owing to probiotic supplementation were reported in any study.
      CONCLUSIONS: Probiotic supplementation showed beneficial effect in the prevention
      and treatment of radiation-induced diarrhea in experimental animal studies.
      Encouraging results have been observed in humans; however, the few available
      clinical studies do not allow firm conclusions. More well-performed, randomized
      placebo-controlled studies are needed.

PMID- 19398931
TI  - A too-long anterior process of the calcaneus: a report of 31 operated cases.
AB  - A too-long anterior process of the calcaneus is one of the causes of repeated
      sprained ankles or painful feet in the child or adolescent that is often ignored
      and misdiagnosed. Among 31 cases of adolescents having consulted for these
      symptoms, a too-long anterior process of the calcaneus was discovered on
      radiographs, and explored in detail with a computed tomography scan or an MRI.
      The decision for surgical resection was taken considering the discomfort
      expressed by these children. The intraoperative observation corroborated the
      radiological findings and permitted a better understanding of the mechanisms
      responsible for the pain, the repeated sprained ankles and other instabilities.
      The surgical resection, which is a simple procedure, gave very good results. One
      must nevertheless be aware of the possible secondary lesions because of repeated
      sprained ankles: breakage of the lateral ligaments of the ankle and external
      malleolus nonunion or talus osteochondritis, which can compromise the operation's
      result, if they are not treated simultaneously.

PMID- 19398932
TI  - Investigating the association between autistic-like and internalizing traits in a
      community-based twin sample.
AB  - OBJECTIVES: Recent research has suggested that children with autistic spectrum
      disorders often experience comorbid symptoms of anxiety and depression. However,
      despite this overlap, no quantitative genetic studies have addressed the
      phenotypic overlap and the etiologic association between internalizing and
      autistic-like traits within the general population. This study aimed to
      investigate the phenotypic and etiologic relation between internalizing and
      autistic-like traits using a community-based twin sample. METHOD: We investigated
      the co-occurrence of these traits in a population-based sample of 3,233 twin
      pairs aged 8 to 9 years, using both parent- and teacher-report questionnaires.
      Bivariate structural equation modeling techniques were used to determine the
      extent to which internalizing and autistic-like traits shared common genetic and
      environmental influences. RESULTS: Our results showed that there was a modest
      phenotypic correlation (r = 0.26-0.29) between autistic-like and internalizing
      traits. The traits were both substantially heritable but were largely independent
      with regard to their genetic influences (r(G) = 0.12-0.19). Shared environmental
      influences were modest but were largely common to both traits. Similar results
      were found using both parent- and teacher-reported data. CONCLUSIONS:
      Internalizing and autistic-like traits showed moderate phenotypic overlap within
      the general population. This association was explained in small part by shared
      genetic factors, but the results suggested that most genetic influences were
      specific to either internalizing traits or autistic traits. Given these findings,
      we discuss the potential mechanisms that may underlie the relation between these
      traits.

PMID- 19398933
TI  - Entrainment of Drosophila circadian clock to green and yellow light by Rh1, Rh5,
      Rh6 and CRY.
AB  - Light is one of the most important time cues for entrainment of the circadian
      clock. Drosophila circadian photoreception is mediated by cryptochrome in clock
      neurons and by rhodopsins in photic organs. We generated Rh5 mutants to elucidate
      circadian photoreception by rhodopsins. The Rh1, Rh5 and Rh6 mutants were
      combined with cry, and entrained to a 6-h delayed photoperiod. The cry, Rh1, Rh5
      and Rh6 quadruple mutant became entrained by white light. In contrast,
      reentrainment to green and yellow light was abolished in the cry, Rh1, Rh5 and
      Rh6 quadruple mutant, and remarkably slowed in the cry, Rh1 and Rh6 triple
      mutant. These results suggest that cry, Rh1, Rh5 and Rh6 are essential for
      circadian photoentrainment to green and yellow light.

PMID- 19398934
TI  - Facilitation of visual processing by masked presentation of a conditioned facial
      stimulus.
AB  - We tested whether a conditioned emotional stimulus could facilitate visual
      processing when presented subliminally. Participants received Pavlovian
      conditioning in which a fearful expression (conditioned stimulus) was paired with
      electric finger shock (unconditioned stimulus). In a subsequent session, they
      were subject to a simple perceptual task involving subliminal presentation of
      facial expressions followed by a simple color patch. Although none of the
      participants reported conscious detection of the facial stimuli, early posterior
      negativity was significantly enhanced to the conditioned fear face and the
      neutral face of the same identity. Paralleling the brain activity, reaction times
      to the conditioned stimulus faces were also facilitated. These results suggest
      that conditioned threat stimuli can facilitate perceptual processing even when
      they are processed unconsciously.

PMID- 19398935
TI  - Interstitial injection of (32)P-chromic phosphate during lung cancer resection to
      treat occult lymphatic metastasis.
AB  - OBJECTIVE: We aimed to study the interstitial injection of (32)P-chromic
      phosphate colloids ((32)P-CP) during lung cancer resection to treat occult
      lymphatic metastasis, and to observe its medium-term and long-term effects.
      METHODS: Seventy-three patients underwent surgery combined with injection of
      (32)P-CP with the dosage of 296-370 MBq/10 ml to the adipose and connective
      tissues neighboring pulmonary hilum, superior mediastinum, carina of trachea, and
      suspicious invaded pleura. Fifty-eight patients underwent only tumor resections
      served as control group. A monofactorial analysis by a chi test was conducted to
      determine the differences in positive rates of lymph nodes, the incidence of
      complications after the operation, the rate of supraclavicular lymph node
      metastasis, and the survival rate between the two groups. The survival curves
      were obtained using the Kaplan-Meier method and were compared by a log-rank test.
      The Cox's multivariate analysis was performed to identify the prognostic factors.
      RESULTS: There was no significant difference between lymph node-positive rates
      and the incidences of major complications (P>0.05). The rate of supraclavicular
      lymph node metastasis in surgery plus (32)P-CP group was prominently lower than
      that in the control group (P<0.05). Three-year and 5-year survival rates of the
      two groups showed significant difference (P<0.05). A Kaplan-Meier analysis
      revealed prominent statistical differences between the two groups (P<0.05). The
      Cox's multivariate analysis showed that the injection of (32)P-CP is one of the
      independent predictors of survival rates. CONCLUSION: Interstitial mediation with
      (32)P-CP during the resection of lung cancer is effective in inhibiting
      postoperative occult lymphatic metastasis, and showed satisfactory effects in
      improving patients' medium-term and long-term survival rates.

PMID- 19398936
TI  - High activity of monoamine oxidase A is associated with externalizing behaviour
      in maltreated and nonmaltreated adoptees.
AB  - Individual differences in a functional polymorphism of the promoter of the
      Monoamine oxidase A (MAO-A) gene might partly explain the increased vulnerability
      of maltreated children for externalizing behaviour. A sample of 239
      internationally adopted boys was studied. Adoptive parents provided the
      information about abuse and neglect before the adoption and rated externalizing
      behaviour of their adopted children, using the Child Behaviour Checklist. MAO-A
      alleles were classified in high and low activity. We found that individuals with
      high MAO-A activity had more externalizing behaviour than those with low MAO-A
      activity. No modifying effect of MAO-A on the relationship between early
      maltreatment on externalizing behaviour was observed. Our results suggest that in
      severely maltreated children, high MAO-A activity may not protect against the
      effects of maltreatment but may convey an increased risk for externalizing
      behaviour.

PMID- 19398937
TI  - The role of vaccination in prevention of VZV disease in the immunocompromised
      child.

PMID- 19398938
TI  - The evolving role of axillary dissection.

PMID- 19398939
TI  - Update of FDA's Critical Path Initiative.

PMID- 19398940
TI  - New drugs in multiple myeloma and the significance of autologous stem cell
      transplants.

PMID- 19398941
TI  - Transverse myelitis: amphiphysin autoimmunity paraneoplastic syndrome in a woman
      with breast cancer.

PMID- 19398942
TI  - Amphiphysin autoimmunity in paraneoplastic neurologic disease.

PMID- 19398943
TI  - Tamoxifen metabolism and its effect on endocrine treatment of breast cancer.
AB  - Tamoxifen is the most common endocrine therapy administered worldwide to women
      with hormone receptor-positive metastatic breast cancer or as adjuvant therapy
      for early stages of the disease. Tamoxifen may also be prescribed to women with
      ductal carcinoma in situ or to decrease the risk of breast cancer in women at
      high risk of developing the disease. While the use of aromatase inhibitors is
      increasing in the postmenopausal treatment setting, tamoxifen remains the drug of
      choice for premenopausal women. Several factors may contribute to reduced benefit
      from tamoxifen. It has been increasingly recognized in recent years that
      pharmacogenetics may play a role in tamoxifen's metabolism, efficacy, and safety.
      Cytochrome P450 (CYP) 2D6 encodes for a liver enzyme that is responsible for the
      conversion of tamoxifen into its active metabolite, endoxifen. Variant alleles in
      CYP2D6 or the use of medications that inhibit the enzyme clearly influence
      tamoxifen's metabolism into endoxifen. In addition, several retrospective studies
      suggest that variants in CYP2D6 may influence long term outcomes. In this review,
      we will summarize recent data that examined associations between CYP2D6 activity
      and effects on tamoxifen's metabolism and efficacy.

PMID- 19398944
TI  - The role of MRI and MRSI in diagnosis, treatment selection, and post-treatment
      follow-up for prostate cancer.
AB  - Magnetic resonance imaging (MRI) is increasingly being recognized as a valuable
      tool for the assessment of prostate cancer. In recent years, MRI technology has
      matured, image acquisition and interpretation have improved, and a multitude of
      clinical studies have demonstrated the potential of MRI techniques for
      contributing to prostate cancer care. This review will provide a brief overview
      of MRI techniques relevant to prostate cancer, including MR spectroscopic
      imaging, and discuss the ways that they can aid in diagnosis, treatment
      selection, and post-treatment follow-up.

PMID- 19398947
TI  - A video demonstration of preserved piloting by scent tracking but impaired dead
      reckoning after fimbria-fornix lesions in the rat.
AB  - Piloting and dead reckoning navigation strategies use very different cue
      constellations and computational processes (Darwin, 1873; Barlow, 1964; O'Keefe
      and Nadel, 1978; Mittelstaedt and Mittelstaedt, 1980; Landeau et al., 1984;
      Etienne, 1987; Gallistel, 1990; Maurer and Se guinot, 1995). Piloting requires
      the use of the relationships between relatively stable external (visual,
      olfactory, auditory) cues, whereas dead reckoning requires the integration of
      cues generated by self-movement. Animals obtain self-movement information from
      vestibular receptors, and possibly muscle and joint receptors, and efference copy
      of commands that generate movement. An animal may also use the flows of visual,
      auditory, and olfactory stimuli caused by its movements. Using a piloting
      strategy an animal can use geometrical calculations to determine directions and
      distances to places in its environment, whereas using an dead reckoning strategy
      it can integrate cues generated by its previous movements to return to a just
      left location. Dead reckoning is colloquially called "sense of direction" and
      "sense of distance." Although there is considerable evidence that the hippocampus
      is involved in piloting (O'Keefe and Nadel, 1978; O'Keefe and Speakman, 1987),
      there is also evidence from behavioral (Whishaw et al., 1997; Whishaw and
      Maaswinkel, 1998; Maaswinkel and Whishaw, 1999), modeling (Samsonovich and
      McNaughton, 1997), and electrophysiological (O'Mare et al., 1994; Sharp et al.,
      1995; Taube and Burton, 1995; Blair and Sharp, 1996; McNaughton et al., 1996;
      Wiener, 1996; Golob and Taube, 1997) studies that the hippocampal formation is
      involved in dead reckoning. The relative contribution of the hippocampus to the
      two forms of navigation is still uncertain, however. Ordinarily, it is difficult
      to be certain that an animal is using a piloting versus a dead reckoning strategy
      because animals are very flexible in their use of strategies and cues (Etienne et
      al., 1996; Dudchenko et al., 1997; Martin et al., 1997; Maaswinkel and Whishaw,
      1999). The objective of the present video demonstrations was to solve the problem
      of cue specification in order to examine the relative contribution of the
      hippocampus in the use of these strategies. The rats were trained in a new task
      in which they followed linear or polygon scented trails to obtain a large food
      pellet hidden on an open field. Because rats have a proclivity to carry the food
      back to the refuge, accuracy and the cues used to return to the home base were
      dependent variables (Whishaw and Tomie, 1997). To force an animal to use a a dead
      reckoning strategy to reach its refuge with the food, the rats were tested when
      blindfolded or under infrared light, a spectral wavelength in which they cannot
      see, and in some experiments the scent trail was additionally removed once an
      animal reached the food. To examine the relative contribution of the hippocampus,
      fimbria-fornix (FF) lesions, which disrupt information flow in the hippocampal
      formation (Bland, 1986), impair memory (Gaffan and Gaffan, 1991), and produce
      spatial deficits (Whishaw and Jarrard, 1995), were used.

PMID- 19398948
TI  - AKT1 represses gene conversion induced by different genotoxic stresses and
      induces supernumerary centrosomes and aneuploidy in hamster ovary cells.
AB  - The oncogenic kinase AKT1 is frequently overexpressed or activated in sporadic
      breast and ovarian cancers. In human breast tumors, we have previously shown that
      AKT1 represses homologous recombination (HR) induced by one double-strand break
      (DSB). To further analyze the impact of AKT1 on HR, we ectopically expressed wild
      type or mutant forms of AKT1 in a hamster ovary cell line containing an
      intrachromosomal substrate for monitoring HR. In this cell line, AKT1 repressed
      HR induced by different genotoxic stresses including ionizing radiation, UV-C and
      one single DSB introduced into the intrachromosomal substrate. Consistently, AKT1
      disrupted RAD51 foci formation, showing that AKT1 specifically affects gene
      conversion. Concomitantly, AKT1 represses both BRCA1 foci formation and HR
      stimulation resulting from BRCA1 overexpression, showing that AKT1 affects BRCA1
      mediated HR functions, also in another species (hamster) and in another type of
      cell tissue (ovary cells). Finally, consistent with the HR defects, active AKT1
      expression induces supernumerary centrosomes and aneuploidy. In addition to its
      impact on cell proliferation and apoptosis, the present data propose a novel
      oncogenic function for AKT1, by producing genomic instability as a consequence of
      HR repression.

PMID- 19398949
TI  - Ribonucleotide reductase small subunit p53R2 suppresses MEK-ERK activity by
      binding to ERK kinase 2.
AB  - The p53-dependent RR small subunit (p53R2) protein, a newly identified member of
      the ribonucleotide reductase family, plays a key role in the p53-dependent
      cellular response to DNA. Several recent studies have suggested that p53R2 also
      plays an important role in suppressing the invasive potential of human cancer
      cells. However, the cellular mechanism that regulates invasiveness remains
      largely unknown. In this study, we show that p53R2 interacts with MEK2
      (extracellular signal-regulated kinase (ERK) kinase 2-mitogen-activated protein
      kinase (MAPK) kinase 2), the molecule immediately upstream of ERK in the Ras-Raf
      MAPK signaling cascade. In co-immunoprecipitation and immunofluorescence
      analyses, we found that p53R2 and MEK2 interact physically in cultured mammalian
      cells, and that the p53R2 segment comprising amino acids 161-206 is critical for
      this interaction. Moreover, serum-induced phosphorylation of MEK1/2 and ERK1/2
      was greatly augmented in human cancer cells expressing small-interfering RNA
      against p53R2. On the other hand, phosphorylation of MEK1/2 and ERK1/2 in human
      cancer cells was markedly attenuated by overexpression of p53R2. Furthermore,
      MEK2 was required for p53R2 knockdown-induced enhancement of the invasive ability
      and anchorage-independent growth of human lung cancer H1299 cells. Taken
      together, these findings show that p53R2 negatively modulates serum-induced MEK
      ERK activity and inhibits the MEK-ERK-mediated malignancy potential of human
      cancer cells.

PMID- 19398950
TI  - Artemis is a negative regulator of p53 in response to oxidative stress.
AB  - Artemis is a multifunctional phospho-protein with roles in V(D)J recombination,
      repair of double-strand breaks by nonhomologous end-joining and regulation of
      cell-cycle checkpoints after DNA damage. Here, we describe a new function of
      Artemis as a negative regulator of p53 in response to oxidative stress in both
      primary cells and cancer cell lines. We show that depletion of Artemis under
      typical culture conditions (21% oxygen) leads to a spontaneous phosphorylation
      and stabilization of p53, and resulting cellular G1 arrest and apoptosis. These
      effects are suppressed by co-depletion of DNA-PKcs, but not ATM, indicating that
      Artemis is an inhibitor of DNA-PKcs-mediated stabilization of p53. Culturing of
      cellsat 3% oxygen or treatment with an antioxidant abrogated p53 stabilization,
      indicating that oxidative stress is the responsible cellular stimulus. Treatment
      with ionizing radiation or hydrogen peroxide did not cause activation of this
      signaling pathway, whereas inhibitors of mitochondrial electron transport were
      effective in reducing its activation. In addition, we show that p53-inducible
      genes involved in reducing reactive oxygen species are upregulated by Artemis
      depletion. These findings indicate that Artemis and DNA-PKcs participate in a
      new, signaling pathway to modulate p53 function in response to oxidative stress
      produced by mitochondrial respiration.

PMID- 19398951
TI  - Beclin 1: a BH3-only protein that fails to induce apoptosis.
AB  - Beclin 1 has been recently shown to possess a Bcl-2 homology-3 (BH3) domain that
      mediates its interaction with antiapoptotic multidomain proteins. Unlike other
      BH3-only proteins, Beclin 1 fails to stimulate apoptosis when it is
      overexpressed. In this issue of Oncogene, Ciechomska et al. report the intriguing
      finding that Bcl-2, as it interacts with Beclin 1, does not lose its anti
      apoptotic potential. This finding may have far-reaching implications for the
      comprehension of the cross-talk between apoptosis and autophagy.

PMID- 19398952
TI  - Suppression of the DNA damage response in acute myeloid leukemia versus
      myelodysplastic syndrome.
AB  - The molecular mechanisms responsible for the evolution from the preleukemic
      entities of low-risk myelodysplastic syndrome (MDS) to the less favorable forms
      of high-risk MDS, as well as those enabling transformation to acute myeloid
      leukemia (AML), are still incompletely understood. Abundant evidence from solid
      tumors demonstrates that preneoplastic lesions activate signaling pathways of a
      DNA damage response (DDR), which functions as an 'anticancer barrier' hindering
      tumorigenesis. Testing the hypothesis that subgroups of MDS and AML differ with
      respect to DDR, we first assessed markers of DDR (phosphorylation of ATM, Chk-1,
      Chk-2 and H2AX) in cell lines representing different entities of MDS (P39, MOLM
      13) and AML (MV4-11, KG-1) before and after gamma-irradiation. Although gamma
      irradiation induced apoptosis and G(2)/M arrest and a concomitant increase in the
      phosphorylation of ATM, Chk-1 and H2AX in MDS-derived cell lines, this radiation
      response was attenuated in the AML-derived cell lines. It is noteworthy that KG
      1, but not P39 cells exhibit signs of an endogenous activation of the DDR.
      Similarly, we found that the frequency of P-ATM(+) cells detectable in bone
      marrow (BM) biopsies increased in samples from patients with AML as compared with
      high-risk MDS samples and significantly correlated with the percentage of BM
      blasts. In contrast, the frequency of gamma-H2AX(+) cells was heterogeneous in
      all subgroups of AML and MDS. Whereas intermediate-1 MDS samples contained as
      little P-Chk-1 and P-Chk-2 as healthy controls, staining for both checkpoint
      kinases increased in intermediate-2 and high-risk MDS, yet declined to near-to
      background levels in AML samples. Thus the activation of Chk-1 and Chk-2 behaves
      in accord with the paradigm established for solid tumors, whereas ATM is
      activated during and beyond transformation. In conclusion, we demonstrate the
      heterogeneity of the DDR response in MDS and AML and provide evidence for its
      selective suppression in AML because of the uncoupling between activated ATM and
      inactive checkpoint kinases.

PMID- 19398953
TI  - DDX1 is required for testicular tumorigenesis, partially through the
      transcriptional activation of 12p stem cell genes.
AB  - Cytogenetic analysis has identified 12p gain as the most frequent abnormality in
      human testicular germ cell tumors (TGCTs). It has been suggested that
      amplification and overexpression of stem cell-associated genes, including cyclin
      D2, on the human chromosome 12p region are involved in germ cell tumorigenesis.
      By subtractive cDNA analysis, we identified Ddx1, a member of the DEAD-box
      protein family, as a gene predominantly expressed in the primordial germ cells of
      mouse embryos. Knockdown of Ddx1 in a mouse spermatogonia-derived cell line, GC
      1spg, by short interference RNA repressed the expression of cyclin-D2, CD9 and
      GDF3 genes. In the mouse cyclin-D2 gene, a genomic DNA region between -348 and 
      329 was responsible for transcriptional activation by DDX1 based on reporter and
      gel shift assays. Similarly, DDX1 knockdown in the human TGCT cell line NEC8
      repressed the expression of stem cell-associated genes localized on chromosome
      12p13.3, including cyclin-D2, CD9 and NANOG. DDX1-knocked-down TGCT cells could
      not form solid tumors in nude mice. Furthermore, in situ hybridization revealed
      that DDX1 mRNA was produced in both seminoma and nonseminoma types of human TGCT
      samples. We conclude that DDX1 is a critical factor for testicular tumorigenesis.

PMID- 19398954
TI  - Hematopoietic stem cell ageing is uncoupled from p16 INK4A-mediated senescence.
AB  - Somatic stem cells are ultimately responsible for mediating appropriate organ
      homeostasis and have therefore been proposed to represent a cellular origin of
      the ageing process-a state often characterized by inappropriate homeostasis.
      Specifically, it has been suggested that ageing stem cells might succumb to
      replicative senescence by a mechanism involving the cyclin-dependent kinase
      inhibitor p16(INK4A). Here, we tested multiple functional and molecular
      parameters indicative of p16(INK4A) activity in primary aged murine hematopoietic
      stem cells (HSCs). We found no evidence that replicative senescence accompanies
      stem cell ageing in vivo, and in line with p16(INK4A) being a critical
      determinant of such processes, most aged HSCs (>99%) failed to express p16(INK4A)
      at the mRNA level. Moreover, whereas loss of epigenetically guided repression of
      the INK4A/ARF locus accompanied replicative senescent murine embryonic
      fibroblasts, such repression was maintained in aged stem cells. Taken together,
      these studies indicate that increased senescence as mediated by the p16(INK4A)
      tumor suppressor has only a minor function as an intrinsic regulator of steady
      state HSC ageing in vivo.

PMID- 19398955
TI  - Melanocytic nevus-like hyperplasia and melanoma in transgenic BRAFV600E mice.
AB  - BRAF, a cellular oncogene and effector of RAS-mediated signaling, is activated by
      mutation in approximately 60% of melanomas. Most of these mutations consist of a
      V600E substitution resulting in constitutive kinase activation. Mutant BRAF thus
      represents an important therapeutic target in melanoma. In an effort to produce a
      pre-clinical model of mutant BRAF function in melanoma, we have generated a mouse
      expressing BRAF V600E targeted to melanocytes. We show that in these transgenic
      mice, widespread benign melanocytic hyperplasia with histological features of
      nevi occurs, with biochemical evidence of senescence. Melanocytic hyperplasia
      progresses to overt melanoma with an incidence dependent on BRAF expression
      levels. Melanomas show CDKN2A loss, and genetic disruption of the CDKN2A locus
      greatly enhances melanoma formation, consistent with collaboration between BRAF
      activation and CDKN2A loss suggested from studies of human melanoma. The
      development of melanoma also involves activation of the Mapk and Akt signaling
      pathways and loss of senescence, findings that faithfully recapitulate those seen
      in human melanomas. This murine model of mutant BRAF-induced melanoma formation
      thus provides an important tool for identifying further genetic alterations that
      cooperates with BRAF and that may be useful in enhancing susceptibility to BRAF
      targeted therapeutics in melanoma.

PMID- 19398956
TI  - Early and delayed castrations confer a similar survival advantage in TRAMP mice.
AB  - The most appropriate time to introduce androgen deprivation therapy for prostate
      cancer remains controversial. Our aim was to evaluate the effects of early versus
      delayed surgical castration on prostate cancer progression and survival in the
      transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice were
      randomly divided into three groups: the early castration group (on which
      castration was performed at the age of 4 weeks), the delayed castration group (on
      which castration was performed when abdominal tumours could be palpated), and the
      sham-castrated group. Mice were monitored daily throughout their lives until
      cancer-related death or the development of an obviously moribund appearance, at
      which time the individual mouse was killed. Androgen receptor expression in
      prostate tumours was also evaluated. The results shows that the average lifespan
      in early castration, delayed castration and sham-castrated groups were 54.1
      weeks, 59.9 weeks and 39.1 weeks, respectively. Both early castration and delayed
      castration conferred a statistically significant survival advantage when compared
      with the sham-castrated group (P<0.001). However, the difference in lifespan
      between the early castration group and the delayed castration group was not
      statistically significant (P=0.85). The increase in lifespan in the TRAMP mice
      that received either early or delayed castration correlated with lower G/B value
      (genitourinary tract weight/body weight) at death than the sham-castrated mice.
      In conclusion, early and delayed castrations in TRAMP mice prolonged survival to
      a similar extent. This finding may provide a guide for clinical practice in
      prostate cancer therapy.

PMID- 19398957
TI  - Two-micron (thulium) laser resection of the prostate-tangerine technique: a new
      method for BPH treatment.
AB  - Two-micron (thulium) laser resection of the prostate-tangerine technique (TmLRP
      TT) is a transurethral procedure that uses a thulium laser fiber to dissect whole
      prostatic lobes off the surgical capsule, similar to peeling a tangerine. We
      recently reported the primary results. Here we introduce this procedure in
      detail. A 70-W, 2-microm (thulium) laser was used in continuous-wave mode. We
      joined the incision by making a transverse cut from the level of the verumontanum
      to the bladder neck, making the resection sufficiently deep to reach the surgical
      capsule, and resected the prostate into small pieces, just like peeling a
      tangerine. As we resected the prostate, the pieces were vaporized, sufficiently
      small to be evacuated through the resectoscope sheath, and the use of the
      mechanical tissue morcellator was not required. The excellent hemostasis of the
      thulium laser ensured the safety of TmLRP-TT. No patient required blood
      transfusion. Saline irrigation was used intraoperatively, and no case of
      transurethral resection syndrome was observed. The bladder outlet obstruction had
      clearly resolved after catheter removal in all cases. We designed the tangerine
      technique and proved it to be the most suitable procedure for the use of thulium
      laser in the treatment of benign prostatic hyperplasia (BPH). This procedure,
      which takes less operative time than standard techniques, is safe and combines
      efficient cutting and rapid organic vaporization, thereby showing the great
      superiority of the thulium fiber laser in the treatment of BPH. It has been
      proven to be as safe and efficient as transurethral resection of the prostate
      (TURP) during the 1-year follow-up.

PMID- 19398958
TI  - Vesicle-mediated secretion of human eosinophil granule-derived major basic
      protein.
AB  - Major basic protein (MBP), the predominant cationic protein of human eosinophil
      specific granules, is stored within crystalloid cores of these granules.
      Secretion of MBP contributes to the immunopathogenesis of varied diseases. Prior
      electron microscopy (EM) of eosinophils in sites of inflammation noted losses of
      granule cores in the absence of granule exocytosis and suggested that eosinophil
      granule proteins might be released through piecemeal degranulation (PMD), a
      secretory process mediated by transport vesicles. Because release of eosinophil
      granule-derived MBP through PMD has not been studied, we evaluated secretion of
      this cationic protein by human eosinophils. Intracellular localizations of MBP
      were studied within nonstimulated and eotaxin-stimulated human eosinophils by
      both immunofluorescence and a pre-embedding immunonanogold EM method that enables
      optimal epitope preservation and antigen access to membrane microdomains. In
      parallel, quantification of transport vesicles was assessed in eosinophils from a
      patient with hypereosinophilic syndrome (HES). Our data demonstrate vesicular
      trafficking of MBP within eotaxin-stimulated eosinophils. Vesicular compartments,
      previously implicated in transport from granules to the plasma membrane,
      including large vesiculotubular carriers termed eosinophil sombrero vesicles
      (EoSVs), were found to contain MBP. These secretory compartments were
      significantly increased in numbers within HES eosinophils. Moreover, in addition
      to granule-stored MBP, even unstimulated eosinophils contained appreciable
      amounts of MBP within secretory vesicles, as evidenced by immunonanogold EM and
      immunofluorescent colocalizations of MBP and CD63. These data suggest that
      eosinophil MBP, with its multiple extracellular activities, can be mobilized from
      granules by PMD into secretory vesicles and both granule- and secretory vesicle
      stored pools of MBP are available for agonist-elicited secretion of MBP from
      human eosinophils. The recognition of PMD as a secretory process to release MBP
      is important to understand the pathological basis of allergic and other
      eosinophil-associated inflammatory diseases.

PMID- 19398959
TI  - Transgenic mitochondrial superoxide dismutase and mitochondrially targeted
      catalase prevent antiretroviral-induced oxidative stress and cardiomyopathy.
AB  - Transgenic mice (TG) were used to define mitochondrial oxidative stress and
      cardiomyopathy (CM) induced by zidovudine (AZT), an antiretroviral used to treat
      HIV/AIDS. Genetically engineered mice either depleted or overexpressed
      mitochondrial superoxide dismutase (SOD2(+/-) KOs and SOD2-OX, respectively) or
      expressed mitochondrially targeted catalase (mCAT). TGs and wild-type (WT)
      littermates were treated (oral AZT, 35 days). Cardiac mitochondrial H(2)O(2),
      aconitase activity, histology and ultrastructure were analyzed. Left ventricle
      (LV) mass and LV end-diastolic dimension were determined echocardiographically.
      AZT induced cardiac oxidative stress and LV dysfunction in WTs. Cardiac
      mitochondrial H(2)O(2) increased and aconitase was inactivated in SOD2(+/-) KOs,
      and cardiac dysfunction was worsened by AZT. Conversely, the cardiac function in
      SOD2-OX and mCAT hearts was protected. In SOD2-OX and mCAT TG hearts,
      mitochondrial H(2)O(2), LV mass and LV cavity volume resembled corresponding
      values from vehicle-treated WTs. AZT worsens cardiac dysfunction and increases
      mitochondrial H(2)O(2) in SOD2(+/-) KO. Conversely, both SOD2-OX and mCAT TGs
      prevent or attenuate AZT-induced cardiac oxidative stress and LV dysfunction. As
      dysfunctional changes are ameliorated by decreasing and worsened by increasing
      H(2)O(2) abundance, oxidative stress from H(2)O(2) is crucial pathogenetically in
      AZT-induced mitochondrial CM.

PMID- 19398960
TI  - Poor vessel formation in embryos from knock-in mice expressing ALK5 with L45 loop
      mutation defective in Smad activation.
AB  - Transforming growth factor (TGF)-beta regulates vascular development through two
      type I receptors: activin receptor-like kinase (ALK) 1 and ALK5, each of which
      activates a different downstream Smad pathway. The endothelial cell (EC)-specific
      ALK1 increases EC proliferation and migration, whereas the ubiquitously expressed
      ALK5 inhibits both of these processes. As ALK1 requires the kinase activity of
      ALK5 for optimal activation, the lack of ALK5 in ECs results in defective
      phosphorylation of both Smad pathways on TGF-beta stimulation. To understand why
      TGF-beta signaling through ALK1 and ALK5 has opposing effects on ECs and whether
      this takes place in vivo, we carefully compared the phenotype of ALK5 knock-in
      (ALK5(KI/KI)) mice, in which the aspartic acid residue 266 in the L45 loop of
      ALK5 was replaced by an alanine residue, with the phenotypes of ALK5 knock-out
      (ALK5(-/-)) and wild-type mice. The ALK5(KI/KI) mice showed angiogenic defects
      with embryonic lethality at E10.5-11.5. Although the phenotype of the ALK5(KI/KI)
      mice was quite similar to that of the ALK5(-/-) mice, the hierarchical structure
      of blood vessels formed in the ALK5(KI/KI) embryos was more developed than that
      in the ALK5(-/-) mutants. Thus, the L45 loop mutation in ALK5 partially rescued
      the earliest vascular defects in the ALK5(-/-) embryos. This study supports our
      earlier observation that vascular maturation in vivo requires both TGF
      beta/ALK1/BMP-Smad and TGF-beta/ALK5/activin-Smad pathways for normal vascular
      development.

PMID- 19398962
TI  - Urinary trypsin inhibitor protects against liver injury and coagulation pathway
      dysregulation induced by lipopolysaccharide/D-galactosamine in mice.
AB  - Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely
      used for patients with inflammatory disorders including disseminated
      intravascular coagulation, shock, and pancreatitis in Japan. Our recent studies
      using UTI-null (-/-) mice have shown that UTI protects against systemic
      inflammatory responses and acute lung injury. However, the role of UTI in liver
      injury has not been elucidated. This study determined the contribution of UTI to
      liver injury and coagulatory disturbance induced by lipopolysaccharide and D
      galactosamine (LPS/D-GalN) using UTI (-/-) and wild-type (WT) mice. LPS/D-GalN
      treatment caused severe liver injury characterized by neutrophilic inflammation,
      hemorrhagic change, necrosis, and apoptosis, which was more prominent in UTI (-/
      ) than in WT mice. In both genotypes of mice, LPS/D-GalN challenge caused
      elevations of aspartate amino-transferase and alanine amino-transferase,
      prolongation of the prothrombin and activated partial thromboplastin time, and
      decreases in fibrinogen and platelet counts, as compared with vehicle challenge.
      These changes, however, were significantly greater in UTI (-/-) than in WT mice.
      Circulatory levels of tumor necrosis factor (TNF)-alpha (P<0.05) and interferon
      (IFN)-gamma were also greater in UTI (-/-) than in WT mice after LPS/D-GalN
      challenge. These results suggest that UTI protects against severe liver injury
      and subsequent coagulatory disturbance induced by LPS/D-GalN, which was mediated,
      at least partly, through the suppression of TNF-alpha production along with its
      antiprotease activity.

PMID- 19398963
TI  - Lower respiratory tract respiratory virus infections increase the risk of
      invasive aspergillosis after a reduced-intensity allogeneic hematopoietic SCT.
AB  - We have analyzed the incidence and risk factors for the occurrence of invasive
      aspergillosis (IA) among 219 consecutive recipients of an allogeneic
      hematopoietic SCT after a reduced-intensity conditioning regimen (Allo-RIC).
      Twenty-seven patients developed an IA at a median of 218 days (range 24-2051)
      post-Allo-RIC, for a 4-year incidence of 13% (95% confidence interval 4-24%). In
      multivariate analysis, risk factors for developing IA were steroid therapy for
      moderate-to-severe graft vs host disease (GVHD) (Hazard Ratio (HR) 2.9, P=0.03),
      occurrence of a lower respiratory tract infection (LRTI) by a respiratory virus
      (RV) (HR 4.3, P<0.01) and CMV disease (HR 2.8, P=0.03). Variables that decreased
      survival after Allo-RIC were advanced disease phase (HR 1.9, P=0.02), steroid
      therapy for moderate-to-severe GVHD (HR 2.2, P<0.01), not developing chronic GVHD
      (HR 4.3, P<0.01), occurrence of LRTI by an RV (HR 3.4, P<0.01) and CMV disease
      (HR 2, P=0.01), whereas occurrence of IA had no effect on survival (P=0.5). Our
      results show that IA is a common infectious complication after an Allo-RIC, which
      occurs late post-transplant and may not have a strong effect on survival. An
      important observation is the possible role of LRTI by conventional RVs as risk
      factors for IA.

PMID- 19398961
TI  - Macrophages of multiple sclerosis patients display deficient SHP-1 expression and
      enhanced inflammatory phenotype.
AB  - Recent studies in mice have demonstrated that the protein tyrosine phosphatase
      SHP-1 is a crucial negative regulator of proinflammatory cytokine signaling, TLR
      signaling, and inflammatory gene expression. Furthermore, mice genetically
      lacking SHP-1 (me/me) display a profound susceptibility to inflammatory CNS
      demyelination relative to wild-type mice. In particular, SHP-1 deficiency may act
      predominantly in inflammatory macrophages to increase CNS demyelination as SHP-1
      deficient macrophages display coexpression of inflammatory effector molecules and
      increased demyelinating activity in me/me mice. Recently, we reported that PBMCs
      of multiple sclerosis (MS) patients have a deficiency in SHP-1 expression
      relative to normal control subjects indicating that SHP-1 deficiency may play a
      similar role in MS as to that seen in mice. Therefore, it became essential to
      examine the specific expression and function of SHP-1 in macrophages from MS
      patients. Herein, we document that macrophages of MS patients have deficient SHP
      1 protein and mRNA expression relative to those of normal control subjects. To
      examine functional consequences of the lower SHP-1, the activation of STAT6,
      STAT1, and NF-kappaB was quantified and macrophages of MS patients showed
      increased activation of these transcription factors. In accordance with this
      observation, several STAT6-, STAT1-, and NF-kappaB-responsive genes that mediate
      inflammatory demyelination were increased in macrophages of MS patients following
      cytokine and TLR agonist stimulation. Supporting a direct role of SHP-1
      deficiency in altered macrophage function, experimental depletion of SHP-1 in
      normal subject macrophages resulted in an increased STAT/NF-kappaB activation and
      increased inflammatory gene expression to levels seen in macrophages of MS
      patients. In conclusion, macrophages of MS patients display a deficiency of SHP-1
      expression, heightened activation of STAT6, STAT1, and NF-kappaB and a
      corresponding inflammatory profile that may be important in controlling
      macrophage-mediated demyelination in MS.

PMID- 19398964
TI  - Successful engraftment following umbilical cord blood transplantation for
      patients with HLA antibody with or without corresponding HLA in the transplanted
      cord blood.

PMID- 19398965
TI  - Kinetics of Th1/Th2 cytokines and lymphocyte subsets to predict chronic GVHD
      after allo-SCT: results of a prospective study.
AB  - The role of different cytokines and cells of immune system in the pathogenesis of
      chronic GVHD (cGVHD) is still controversial. Earlier studies, which were either
      retrospective or analysed one or a few factors, did not show unequivocal results.
      We prospectively evaluated cytokine levels and lymphocyte subsets in 30 patients
      who underwent Allo-SCT to investigate their possible correlation with cGVHD.
      Levels of IL-4, IL-6, IL-10, IFN-gamma, tumour necrosis factor-alpha (TNF-alpha)
      and its soluble receptors were assessed by ELISA in 30 patients at different
      times after SCT. Lymphocyte subsets were evaluated by flow cytometry in
      peripheral blood at the same times as cytokines. A multivariate analysis was
      performed using principal component analysis and multi-factor ANOVA (analysis of
      variance). Eighteen patients developed cGVHD at a median time of 6 months (range,
      5-9) after SCT. In multivariate analysis, we observed a correlation between cGVHD
      and clusters of cytokines and lymphocyte subsets from the third to the sixth
      month after SCT. These clusters changed their composition over time, but they
      constantly included natural killer (NK) and CD152+ T cells as negative predictors
      of cGVHD. TNF-alpha prevailed among other cytokines before the onset of cGVHD.
      This prevalence could be related partly to the defect of immunoregulatory cells.

PMID- 19398966
TI  - Effect of iron overload and iron-chelating therapy on allogeneic hematopoietic
      SCT in children.
AB  - Iron overload is known to increase complications of hematopoietic SCT (HSCT). We
      investigated the association of pre-transplant ferritin level with complications
      and survival after allogeneic HSCT, and evaluated the efficacy of iron-chelating
      therapy before HSCT. We retrospectively reviewed 101 patients who underwent
      allogeneic HSCT and divided these patients into three groups: F>1000, patients
      with ferritin level above 1000 ng/ml at the time of HSCT; F<1000, patients whose
      ferritin levels were maintained below 1000 ng/ml before HSCT without iron
      chelating therapy; IC, patients with ferritin level decreased to less than 1000
      ng/ml after iron-chelating therapy before HSCT. In the comparison between the
      F>1000 group and the F<1000 group, hyperbilirubinemia and treatment-related
      mortality (TRM) were significantly higher in the F>1000 group. The F>1000 group
      also showed decreased OS and EFS. In the comparison of the F<1000 and IC groups,
      there was no significant difference in complications and survival. When compared
      with the F>1000 group, the IC group showed lower TRM and higher survival.
      Elevated serum ferritin level was associated with increased TRM and decreased
      survival, and the analysis of the IC group suggested the benefit of iron
      chelating therapy to improve the outcome of HSCT.

PMID- 19398998
TI  - Ovarian hyperstimulation syndrome associated with fetal trisomy 21.
AB  - We report a case of ovarian hyperstimulation syndrome associated with fetal
      trisomy 21. A primigravida presented at 17 1/7 weeks of gestation with abdominal
      pain because of enlarged ovaries. Multiple fetal abnormalities were seen on
      pregnancy ultrasound. Fetal trisomy 21 was diagnosed by amniocentesis. The
      patient's human chorionic gonadotropin level was markedly elevated, as often
      occurs with fetal trisomy 21, and was likely associated with the ovarian
      hyperstimulation. Ovarian hyperstimulation syndrome associated with fetal
      aneuploidy has not been previously described.

PMID- 19398967
TI  - Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell
      niche.
AB  - The in vitro analysis of intestinal epithelium has been hampered by a lack of
      suitable culture systems. Here we describe robust long-term methodology for small
      and large intestinal culture, incorporating an air-liquid interface and
      underlying stromal elements. These cultures showed prolonged intestinal
      epithelial expansion as sphere-like organoids with proliferation and multilineage
      differentiation. The Wnt growth factor family positively regulates proliferation
      of the intestinal epithelium in vivo. Accordingly, culture growth was inhibited
      by the Wnt antagonist Dickkopf-1 (Dkk1) and markedly stimulated by a fusion
      protein between the Wnt agonist R-spondin-1 and immunoglobulin Fc (RSpo1-Fc).
      Furthermore, treatment with the gamma-secretase inhibitor dibenzazepine and
      neurogenin-3 overexpression induced goblet cell and enteroendocrine cell
      differentiation, respectively, consistent with endogenous Notch signaling and
      lineage plasticity. Epithelial cells derived from both leucine-rich repeat
      containing G protein-coupled receptor-5-positive (Lgr5(+)) and B lymphoma moloney
      murine leukemia virus insertion region homolog-1-positive (Bmi1(+)) lineages,
      representing putative intestinal stem cell (ISC) populations, were present in
      vitro and were expanded by treatment with RSpo1-Fc; this increased number of
      Lgr5(+) cells upon RSpo1-Fc treatment was subsequently confirmed in vivo. Our
      results indicate successful long-term intestinal culture within a
      microenvironment accurately recapitulating the Wnt- and Notch-dependent ISC
      niche.

PMID- 19399000
TI  - H-type tracheoesophageal fistula in an extremely low birth weight premature
      neonate: appearance on magnetic resonance imaging.
AB  - Many diagnostic methods have been used to establish the diagnosis for a suspected
      H-type tracheoesophageal fistula (TEF). In case of a strong assumption of an H
      type fistula, besides all standard diagnostic work-up tools a more aggressive
      combined approach is advisable. However, in a critically ill premature infant,
      conventional invasive investigations could not be performed as being potentially
      hazardous and not always easy to achieve. We describe the unique imaging features
      of an H-type TEF on magnetic resonance imaging (MRI). Our case demonstrates that
      MR images could be used for diagnosis, and localization of an H-type TEF could be
      detected safely and accurately in a sick preterm infant.

PMID- 19398999
TI  - Galactorrhea with metoclopramide use in the neonatal unit.
AB  - We report a 3(1/2)-month-old infant with trisomy 21 presenting with galactorrhea
      in the neonatal intensive care unit (NICU). Endocrine work-up showed a high
      prolactin level (64.4 ng ml(-1)--normal: 0.5 to 30 ng ml(-1)). Cessation of
      therapy with metoclopramide (0.2 mg kg(-1) per dose q 6 h) resulted in the
      resolution of galactorrhea with a decrease in serum prolactin level (20.1 ng ml(
      1)). We present this case to highlight this uncommon side effect of a commonly
      used medication in the NICU.

PMID- 19399001
TI  - Massive congenital orbital teratoma.

PMID- 19399002
TI  - Proceedings of the 5th Annual Conference on Evidence vs Experience in Neonatal
      Practices, June 2008, Chicago, Illinois, USA.

PMID- 19399003
TI  - Late preterm infants: severe hyperbilirubinemia and postnatal glucose
      homeostasis.
AB  - The identification of late preterm infants as a high-risk group of infants has
      been an important public health breakthrough. These infants have suffered a
      relative 'silent morbidity and mortality' before the recognition that they have
      unique physiology and risks. These infants represent almost three-fourths of all
      premature births in the United States. Many of these infants, because of their
      birthweight and appearance, have been treated in Well Baby Nurseries and even
      discharged by 48 h of birth despite specific unidentified or unappreciated risks
      that have led to their readmission and possible severe morbidities or even death.
      Two common problems for these infants include neonatal hypoglycemia and severe
      hyperbilirubinemia. The definition of hypoglycemia remains controversial but is
      nonetheless a problem of increasing frequency in these infants.

PMID- 19399004
TI  - The role of surfactant treatment in preterm infants and term newborns with acute
      respiratory distress syndrome.
AB  - Surfactant treatment in preterm infants and term newborns with (acute respiratory
      distress syndrome) ARDS-like severe respiratory failure has become part of an
      individualized treatment strategy in many intensive care units around the world.
      These babies constitute heterogeneous groups of gestational ages, lung maturity,
      as well as of the underlying disease processes and postnatal interventions. The
      pathophysiology of respiratory failure in preterm infants is characterized by a
      combination of primary surfactant deficiency and surfactant inactivation as a
      result of plasma proteins leaking into the airways from areas of epithelial
      disruption and injury. Various pre- and postnatal factors, such as exposure to
      chorioamnionitis, pneumonia, sepsis and asphyxia, induce an injurious
      inflammatory response in the lungs of preterm infants, which may subsequently
      affect surfactant function, synthesis and alveolar stability. Surfactant
      inactivation--and dysfunction--is also a hallmark in newborns with meconium
      aspiration syndrome (MAS), pneumonia and other disorders affecting the pulmonary
      function. Although for the majority of suggested indications no data from
      randomized controlled trials exist, a surfactant replacement that counterbalances
      surfactant inactivation seems to improve oxygenation and lung function in many
      babies with ARDS without any apparent negative side effects. Newborns with MAS
      will definitely benefit from a reduced need for extracorporeal membrane
      oxygenation (ECMO). Clinical experience seems to justify surfactant treatment in
      neonates with ARDS.

PMID- 19399005
TI  - Probiotic and prebiotic supplementation for the prevention of neonatal
      necrotizing enterocolitis.
AB  - The pathophysiology of necrotizing enterocolitis (NEC) has not been clearly
      elucidated, but recent studies support the role of unbalanced pro-inflammatory
      signaling, leading to intestinal necrosis in premature infants. Although breast
      milk feeding is thought to reduce the risk of this condition, there are no
      preventive or therapeutic approaches that have consistently shown to be effective
      for this common and devastating disease. Recent studies show that probiotic
      colonization is abnormal in preterm neonates, and enteral supplementation with a
      variety of probiotic organisms can reduce the risk of disease. This chapter
      summarizes the current state-of-the-art regarding probiotics and NEC, but
      suggests caution until appropriately regulated products are available for use in
      this high-risk population.

PMID- 19399006
TI  - Synthetic surfactants: where are we? Evidence from randomized, controlled
      clinical trials.
AB  - The benefits of exogenous synthetic or animal-derived surfactants for prevention
      or treatment of respiratory distress syndrome (RDS) are well established. Data
      from head-to-head trials comparing animal-derived surfactants primarily with the
      synthetic surfactant colfosceril suggest that the major clinical advantages
      afforded by the presence of surfactant protein (SP)-B and SP-C in animal-derived
      preparations relate to faster onset of action, a reduction in the incidence of
      RDS when used prophylactically, and a lower incidence of air leaks and RDS
      related deaths. However, no benefits in terms of overall mortality or BPD have
      been shown in these head-to-head comparisons. Findings from trials of a new
      generation synthetic surfactant containing a peptide that mimics SP-B, as well as
      their follow-up study suggest that its administration improves short-term
      clinical outcomes compared with colfosceril and results in survival through 1
      year of age, which is at least comparable, if not perhaps superior, to that seen
      with animal-derived surfactants.

PMID- 19399007
TI  - Pulmonary surfactant kinetics of the newborn infant: novel insights from studies
      with stable isotopes.
AB  - Deficiency or dysfunction of the pulmonary surfactant plays a critical role in
      the pathogenesis of respiratory diseases of the newborn. After a short review of
      the pulmonary surfactant, including its role in selected neonatal respiratory
      conditions, we describe a series of studies conducted by applying two recently
      developed methods to measure surfactant kinetics. In the first set of studies,
      namely 'endogenous studies', which used stable isotope-labeled intravenous
      surfactant precursors, we have shown the feasibility of measuring surfactant
      synthesis and kinetics in infants using several metabolic precursors, including
      plasma glucose, plasma fatty acids and body water. In the second set of studies,
      namely 'exogenous studies', which used a stable isotope-labeled
      phosphatidylcholine (PC) tracer given endotracheally, we estimated the surfactant
      disaturated phosphatidylcholine (DSPC) pool size and half-life. The major
      findings of our studies are presented here and can be summarized as follows: (a)
      the de novo synthesis and turnover rates of the surfactant (DSPC) in preterm
      infants with respiratory distress syndrome (RDS) are very low with either
      precursor; (b) in preterm infants with RDS, pool size is very small and half-life
      much longer than what has been reported in animal studies; (c) patients
      recovering from RDS who required higher continuous positive airway pressure
      pressure after extubation or reintubation have a lower level of intrapulmonary
      surfactant than those who did well after extubation; (d) term newborn infants
      with pneumonia have greatly accelerated surfactant catabolism; and (e) infants
      with uncomplicated congenital diaphragmatic hernia (CDH) and on conventional
      mechanical ventilation have normal surfactant synthesis, but those requiring
      extracorporeal membrane oxygenated (ECMO) do not. Information obtained from these
      studies in infants will help to better tailor exogenous surfactant treatment in
      neonatal lung diseases.

PMID- 19399008
TI  - Animal-derived surfactants: where are we? The evidence from randomized,
      controlled clinical trials.
AB  - Animal-derived surfactants, as well as synthetic surfactants, have been
      extensively evaluated in the treatment of respiratory distress syndrome (RDS) in
      preterm infants. Three commonly available animal-derived surfactants in the
      United States include beractant (BE), calfactant (CA) and poractant alfa (PA).
      Multiple comparative studies have been performed using these three surfactants.
      Prospective as well as retrospective studies comparing BE and CA have shown no
      significant differences in clinical or economic outcomes. Randomized, controlled
      clinical trials have shown that treatment with PA is associated with rapid
      weaning of oxygen and ventilatory pressures, fewer additional doses, cost
      benefits and survival advantage when compared with BE or CA. Recently, a study
      using an administrative database that included over 20,000 preterm infants has
      shown a significant decrease in mortality and cost benefits in favor of PA, when
      compared with BE or CA. Differences in outcomes between these animal-derived
      surfactants may be related to a higher amount of phospholipids and plasmalogens
      in PA. To date, animal-derived surfactants seem to be better than synthetic
      surfactants during the acute phase of RDS and in decreasing neonatal mortality.
      Further studies are needed comparing animal-derived surfactants with the newer
      generation of synthetic surfactants.

PMID- 19399009
TI  - Relative adrenal insufficiency in the preterm and term infant.
AB  - Cortisol release in the face of illness or stress is vital for survival. Relative
      adrenal insufficiency occurs when a patient's cortisol response is inadequate for
      the degree of illness or stress. Numerous studies have documented the existence
      of relative adrenal insufficiency in critically ill adults, and its association
      with increased morbidity and mortality. There is increasing evidence that
      relative adrenal insufficiency may be an etiology for hemodynamic instability and
      hypotension in the critically ill newborn, but compared with the adult
      population, there is still a paucity of data in this population. Randomized
      controlled trials are needed to evaluate the efficacy and safety of
      glucocorticoids for the treatment of cardiovascular insufficiency due to relative
      adrenal insufficiency in ill preterm and term newborn infants.

PMID- 19399010
TI  - Support of the preterm circulation: keynote address to the Fifth Evidence vs
      Experience Conference, Chicago, June 2008.
AB  - Hemodynamics is an area of neonatology that is marked more by what we do not know
      than what we do. What is clear is that it is much more complex than just
      measuring blood pressure (BP). Early postnatal preterm hemodynamic
      pathophysiology is characterized by low systemic blood flow (SBF), possibly
      relating to a mix of afterload compromise, left-to-right shunting through the
      unconstricted ductus and to the circulatory effects of ventilation. After
      approximately 24 h of age, vasodilatation seems to be the dominant pathology. In
      the face of this complexity, a one-size-fits-all approach to treatment that will
      be applicable in a large clinical trial may prove elusive. The possibility of
      using a measure of both BP and SBF to target an appropriate treatment needs to be
      explored.

PMID- 19399011
TI  - Definition of hypotension and assessment of hemodynamics in the preterm neonate.
AB  - The complexity of postnatal cardiovascular transition has only recently been
      better appreciated in the very low birth weight neonate. As blood pressure in
      itself poorly represents systemic blood flow, especially when the fetal channels
      are open and the developmentally regulated vital organ assignment may not have
      been completed, efforts to measure systemic blood flow have resulted in a novel,
      yet incomplete, understanding of the principles and clinical relevance of
      cardiovascular adaptation during postnatal transition in this patient population.
      This article describes the definition of hypotension based on the principles of
      cardiovascular physiology, and reviews the tools available to the clinician and
      researcher at the bedside to examine the complex relationship among blood
      pressure, systemic and organ blood flow, and tissue oxygen delivery and oxygen
      demand in vital and non-vital organs in the very low birth weight neonate. Only
      after gaining an insight into these complex relationships and processes will we
      be able to design clinical trials of selected treatment modalities targeting
      relevant patient sub-populations for the management of neonatal cardiovascular
      compromise. Only clinical trials based on a solid understanding of developmental
      cardiovascular physiology tailored to the appropriate patient sub-population hold
      the promise of being effective and practical, and can lead to improvements in
      both hemodynamic parameters and clinically relevant outcome measures.

PMID- 19399012
TI  - Inhaled nitric oxide in the neonate.
AB  - Inhaled nitric oxide (iNO) has been used to treat both term and preterm infants
      with respiratory failure. Term infants with persistent pulmonary hypertension,
      either as a primary cause or secondary to other disease processes, respond to iNO
      with improvement in oxygenation indices and a decreased need for extracorporeal
      membrane oxygenation. Infants with congenital diaphragmatic hernia are the
      exception to this finding, with little clinical benefit observed with iNO
      treatment. Although respiratory disease in preterm infants has a component of
      increased pulmonary vascular resistance, little benefit of iNO administration has
      been observed in premature infants either early in their course or later as a
      treatment to prevent the evolution of chronic lung disease.

PMID- 19399013
TI  - To tube or not to tube babies with respiratory distress syndrome.
AB  - The use of mechanical ventilation in premature infants with respiratory distress
      syndrome (RDS) and respiratory failure often results in barotrauma, volutrauma
      and chronic lung disease (CLD). Research indicates that early surfactant therapy
      and initiation of nasal continuous positive airway pressure (CPAP) for these
      infants significantly reduces the need for mechanical ventilation and the
      incidence of CLD. Different CPAP delivery systems exist, each with some practical
      and clinical advantages and disadvantages. Clinical trials indicate that optimal
      management of neonatal RDS could be improved by early surfactant treatment
      followed immediately by extubation and stabilization on CPAP. Evidence suggests a
      synergistic effect between early surfactant administration (within 2 h of birth)
      and rapid extubation to nasal CPAP with a significant reduction in the need for
      mechanical ventilation and its associated morbidities.

PMID- 19399014
TI  - GERD or not GERD: the fussy infant.
AB  - A global evidence-based consensus has defined gastroesophageal reflux disease
      (GERD) as 'a condition, which develops when the reflux of stomach contents causes
      troublesome symptoms and/or complications.' The manifestations of GERD can be
      divided into esophageal and extraesophageal syndromes, and include vomiting, poor
      weight gain, dysphagia, abdominal or substernal/retrosternal pain, esophagitis
      and respiratory disorders. The extraesophageal syndromes have been divided into
      established and proposed associations: established would include cough,
      laryngitis, asthma and dental erosion ascribable to reflux, whereas proposed
      associations would include pharyngitis, sinusitis, idiopathic pulmonary fibrosis
      and recurrent otitis media. Uninvestigated patients with esophageal symptoms
      without evidence of esophageal injury would be considered to have asymptomatic
      esophageal syndromes, whereas those with demonstrable injury are considered to
      have esophageal syndromes with esophageal injury. Therefore, this allows symptoms
      to define the disease but permits further characterization if mucosal injury is
      found. Within the syndromes with associated injury are reflux esophagitis,
      stricture, Barrett's esophagitis and adenocarcinoma. This review will address
      definitions of GER and GERD-associated symptoms and treatment options.

PMID- 19399015
TI  - Neonatal ventilators: how do they differ?
AB  - Remarkable technological advances over the past two decades have brought dramatic
      changes to the neonatal intensive care unit. Microprocessor-based mechanical
      ventilation has replaced time-cycled, pressure-limited, intermittent mandatory
      ventilation with almost limitless options for the management of respiratory
      failure in the prematurely born infant. Unfortunately, much of the infusion of
      technology occurred before the establishment of a convincing evidence base. This
      review focuses on the basic principles of mechanical ventilation, nomenclature
      and the characteristics of both conventional and high-frequency devices.

PMID- 19399016
TI  - Trans fatty acids: effects on metabolic syndrome, heart disease and diabetes.
AB  - The major dietary sources of trans fatty acids (TFAs) in most countries are
      partially hydrogenated vegetable oils. TFA consumption is a modifiable dietary
      risk factor for metabolic syndrome, diabetes mellitus, and coronary heart
      disease. Here, we review the available data on various effects of TFAs, including
      metabolic and signaling pathways that mediate these effects, affected tissues,
      and relationships with clinical end points. TFA consumption causes metabolic
      dysfunction: it adversely affects circulating lipid levels, triggers systemic
      inflammation, induces endothelial dysfunction, and, according to some studies,
      increases visceral adiposity, body weight, and insulin resistance. Dietary TFAs
      influence the function of multiple cell types, including hepatocytes, adipocytes,
      macrophages and endothelial cells. Among dietary fats and nutrients, TFAs seem to
      have a unique cardiometabolic imprint that is linked to insulin-resistance and
      metabolic-syndrome pathways. Consistent with these adverse physiological effects,
      consumption of even small amounts of TFAs (2% of total energy intake) is
      consistently associated with a markedly increased incidence of coronary heart
      disease. Relationships between TFA consumption and diabetes mellitus have been
      less consistent, possibly owing to differences in study designs. Nevertheless,
      the documented adverse effects of TFAs underscore their potential to cause harm
      and the importance of policy measures to minimize consumption of industrially
      produced TFAs.

PMID- 19399017
TI  - The role of interleukins in insulin resistance and type 2 diabetes mellitus.
AB  - In the past few years, several interleukins (ILs) attracted considerable
      attention as potential effectors in the pathology and physiology of insulin
      resistance associated with type 2 diabetes mellitus (T2DM) and obesity. IL-1, a
      major proinflammatory cytokine, is present at increased levels in patients with
      diabetes mellitus, and could promote beta-cell destruction and alter insulin
      sensitivity. The effects of IL-1 are likely to be counteracted by IL-1 receptor
      antagonist protein (IL-1ra), as suggested by interventional studies in patients
      with T2DM who were treated with a recombinant form of this protein. However,
      studies in IL-1ra-deficient mice provided controversial results on the exact
      effect of the IL-1 signaling pathway on insulin secretion, insulin sensitivity
      and accumulation of adipose tissue. Likewise, IL-6 has been suggested to be
      involved in the development of obesity-related and T2DM-related insulin
      resistance. The action of IL-6 on glucose homeostasis is also complex and
      integrates central and peripheral mechanisms. Both experimental and clinical
      studies now converge to show that several ILs contribute to the pathology and
      physiology of T2DM through their interaction with insulin signaling pathways and
      beta-cell function.

PMID- 19399018
TI  - Unusual renal presentation of Fabry disease in a female patient.
AB  - BACKGROUND: A 29-year-old white woman with a family history of Fabry disease was
      referred to a nephrology clinic with hypertension and nephropathy. Her renal
      function was below normal (serum creatinine level 141 micromol/l; estimated
      glomerular filtration rate 41 ml/min/1.73 m2) with no proteinuria or albuminuria.
      INVESTIGATIONS: Medical history, physical examination, leukocyte alpha
      galactosidase A assay, laboratory tests (for antinuclear antibodies,
      antineutrophil cytoplasmic antibodies, lupus anticoagulant, anticardiolipin
      antibodies, complement and cryoglobulin), ophthalmological examination,
      echocardiography, brain magnetic resonance angiography, renal ultrasonography,
      renal color echo-Doppler scan, renal magnetic resonance angiography, renal
      angiography and renal biopsy. DIAGNOSIS: Diffuse sclero-atrophic renal tissue
      changes and widespread renal arterio-arteriolosclerotic changes secondary to
      Fabry disease. TREATMENT: Angiotensin-converting-enzyme inhibitors and
      maintenance treatment with agalsidase-beta, 1 mg/kg body weight, every 2 weeks.

PMID- 19399019
TI  - ANCA-negative pauci-immune crescentic glomerulonephritis.
AB  - Crescentic glomerulonephritis is a severe form of glomerular injury that is
      characterized by disruption of the glomerular basement membrane, cellular
      proliferation within Bowman space, and (often) fibrinoid necrosis. Pauci-immune
      crescentic glomerulonephritis, so called because it involves little or no
      glomerular immunoglobulin deposition, is one of the most common causes of rapidly
      progressive glomerulonephritis. In the majority of patients, pauci-immune
      crescentic glomerulonephritis is a manifestation of antineutrophil cytoplasmic
      antibody (ANCA)-associated vasculitis. However, some patients with pauci-immune
      crescentic glomerulonephritis lack ANCAs. This Review compares the prevalence,
      clinical manifestations, histopathology, and outcomes of ANCA-negative pauci
      immune crescentic glomerulonephritis with those of ANCA-positive disease. We also
      discuss the possible pathogenesis of ANCA-negative pauci-immune crescentic
      glomerulonephritis, paying particular attention to the mechanisms and role of
      neutrophil activation.

PMID- 19399021
TI  - Psychometric analysis of the Three-Factor Eating Questionnaire-R21: results from
      a large diverse sample of obese and non-obese participants.
AB  - BACKGROUND: The 21-item Three-Factor Eating Questionnaire (TFEQ-R21) is a scale
      that measures three domains of eating behavior: cognitive restraint (CR),
      uncontrolled eating (UE) and emotional eating (EE). OBJECTIVES: To assess the
      factor structure and reliability of TFEQ-R21 (and if necessary, refine the
      structure) in diverse populations of obese and non-obese individuals. DESIGN:
      Data were obtained from obese adults in a United States/Canadian clinical trial
      (n=1741), and overweight, obese and normal weight adults in a US web-based survey
      (n=1275). Confirmatory factor analyses were employed to investigate the structure
      of TFEQ-R21 using baseline data from the clinical trial. The model was refined to
      obtain adequate fit and internal consistency. The refined model was then tested
      using the web-based data. Relationships between TFEQ domains and body mass index
      (BMI) were examined in both populations. RESULTS: Clinical data indicated that
      TFEQ-R21 needed refinement. Three items were removed from the CR domain,
      producing the revised version TFEQ-R18V2 (Comparative Fit Index (CFI)=0.91).
      Testing TFEQ-R18V2 in the web-based sample supported the revised structure
      (CFI=0.96; Cronbach's coefficient alpha of 0.78-0.94). Associations with BMI were
      small. In the clinical study, the CR domain showed a significant and negative
      association with BMI. On the basis of the web-based survey, it was shown that the
      relationship between BMI and CR is population-dependent (obese versus non-obese,
      healthy versus diabetics). CONCLUSIONS: In two independent datasets, the TFEQ
      R18V2 showed robust factor structure and good reliability. It may provide a
      useful tool for characterizing UE, CR and EE.

PMID- 19399020
TI  - Modifiable risk factors in relation to changes in BMI and fatness: what have we
      learned from prospective studies of school-aged children?
AB  - Considerable interest and resources are currently being directed to primary and
      secondary prevention of childhood obesity among school-aged children.
      Intervention studies in this age group have yielded mixed results, begging the
      question as to whether the correct targets for intervention have been identified.
      To evaluate the evidence base, we reviewed prospective observational studies
      published in English between 1990-2007 that reported weight or fatness changes in
      relation to diet, physical activity, and sedentary behavior. Sugar-sweetened
      beverage consumption emerged as the most consistent dietary factor in association
      with subsequent increases in weight status or fatness. Other foods and eating
      patterns showed less consistent associations and when associations were present,
      magnitudes were generally small. This may reflect the known limitations of
      standard dietary methodology to assess meal patterns and dietary intake. Findings
      for physical activity showed more consistent inverse associations with fatness
      outcomes than for weight status, and as was found for dietary factors, magnitudes
      of association were modest. Sedentary behavior effects on weight status differ by
      gender in many studies, with many, but not all, showing greater positive
      associations among girls. The lack of consistency observed in the studies of
      sedentary behaviors may reflect the range of variable definitions, measurement
      challenges, and the changing nature of electronic media. The intrinsic interplay
      among eating patterns, activity and sedentary behavior adds further complexity to
      the interpretation of the results of these studies. More sophisticated approaches
      to the analysis of these complex data in future studies may maximize what is
      learned. Although the classic obesity risk factors seem to play a role in the
      development of excess weight and fatness, some more recently identified potential
      factors, such as sleep, warrant further investigation in prospective studies
      before they are ready for evaluation using more controlled study designs.

PMID- 19399022
TI  - Several obesity- and nutrient-related gene polymorphisms but not FTO and UCP
      variants modulate postabsorptive resting energy expenditure and fat-induced
      thermogenesis in obese individuals: the NUGENOB study.
AB  - BACKGROUND: Part of the heterogeneity of the obesity phenotype may originate from
      genetic differences between obese individuals that may influence energy
      expenditure (EE). OBJECTIVE: To examine if common single-nucleotide polymorphisms
      (SNPs) in genes related to obesity-associated phenotypes are associated with
      postabsorptive resting energy expenditure (REE) and postprandial REE in obese
      individuals. DESIGN AND METHODS: Postabsorptive REE and 3-h postprandial REE
      (liquid test meal containing 95% fat, energy content 50% of estimated REE) were
      measured in 743 obese individuals from eight clinical centres in seven European
      countries. The analysis assessed the association of genotypes of 44 SNPs in 28
      obesity-related candidate genes with postabsorptive REE and postprandial REE
      taking into consideration the influence of body composition, habitual physical
      activity, insulin sensitivity, circulating thermogenic hormones and metabolites.
      RESULTS: After adjustment for fat-free mass (FFM), age, sex and research centre,
      SNPs in CART, GAD2, PCSK1, PPARG3, HSD11B1 and LIPC were significantly associated
      with postabsorptive REE. SNPs in GAD2, HSD11B1 and LIPC remained significantly
      associated with postabsorptive REE after further adjustment for fat mass (FM).
      SNPs in CART, PPARG2 and IGF2 were significantly associated with postprandial REE
      after similar adjustments. These associations with postprandial REE remained
      significant after further adjustment for FM. FTO, UCP2 and UCP3 variants were not
      associated with postabsorptive or postprandial REE. CONCLUSIONS: Several gene
      polymorphisms associated with obesity-related phenotypes but not FTO and UCP
      variants may be responsible for some of the inter-individual variability in
      postabsorptive REE and fat-induced thermogenesis unaccounted for by FFM, FM, age
      and sex. The association between FTO and obesity that has been reported earlier
      may not be mediated directly through modulation of EE in obese individuals.

PMID- 19399024
TI  - Comparison of depression, anxiety and stress in persons with traumatic and non
      traumatic post-acute spinal cord injury.
AB  - STUDY DESIGN: Community cross-sectional self-report survey of adults with spinal
      cord injury (SCI). OBJECTIVES: The aim of this study was to examine the
      likelihood of depression, anxiety and stress in adults with non-traumatic SCI (NT
      SCI) compared with adults with traumatic SCI (T-SCI). SETTING: Victoria,
      Australia. Adults (N=443; NT-SCI n=62) living in the community and attending
      specialist SCI rehabilitation clinics. METHODS: Participants completed a self
      report survey by internet, telephone or hard copy. Items included demographic and
      injury-related characteristics and the short form Depression, Anxiety and Stress
      Scale (DASS-21). RESULTS: Persons with NT-SCI were significantly more likely to
      be female (P<0.05), older (P<0.001) and have lower-level incomplete injuries
      (P<0.001). The probability of depression, anxiety or stress in respondents with
      NT-SCI did not differ from persons with T-SCI (P>0.05). Overall, the prevalence
      of adverse mental health problems defined by scoring above DASS-21 cutoffs, were
      depression 37%, anxiety 30%, and clinically significant stress 25%. CONCLUSIONS:
      This study examined multiple mental health outcomes after NT-SCI in Australia.
      This study provides some evidence that the results of studies of depression,
      anxiety or stress in persons with T-SCI can be generalised to those with NT-SCI
      in the post-acute phase. NT-SCI patients are also at substantial risk of poor
      mental health outcomes. General demographic and injury-related characteristics do
      not seem to be important factors associated with the mental health of adults with
      SCI whether the SCI is traumatic or non-traumatic in origin.

PMID- 19399026
TI  - IL-21 comes of age.

PMID- 19399025
TI  - Sonographic measurement of diaphragm movement in patients with tetraplegia.
AB  - STUDY DESIGN: This was an observational, descriptive case-series study. The
      magnitude and direction of diaphragm movement during tidal and maximal
      inspiratory breaths in tetraplegic subjects were measured using B-mode sonography
      on a single occasion. Data were tabulated for descriptive analysis. OBJECTIVE:
      There is a paucity of literature reporting dynamic movements of the paralyzed
      diaphragm. The aim of this pilot study was to investigate and record diaphragm
      movement in subjects with a cervical spinal cord injury (C1-C5), which had
      resulted in tetraplegia with partial or complete diaphragm paralysis. Subjects
      were patients of the Royal Adelaide Hospital in South Australia. RESULTS: Three
      subjects participated in the study. The magnitude of diaphragm movement was small
      in two subjects and approached normal in one subject. During tidal inspiratory
      and maximal inspiratory breaths, the diaphragm moved in a caudal direction in two
      subjects. In the other subject, the diaphragm moved in a cephalad direction
      during a maximal inspiratory breath. CONCLUSION: Imaging of diaphragm movement
      was well tolerated by three subjects with cervical spinal cord injury. The
      difference in magnitude of diaphragm movement was not fully explained by the
      level of injury and the American Spinal Injury Association classification.

PMID- 19399023
TI  - Cancer micrometastases.
AB  - Early spread of tumor cells is usually undetected by current imaging
      technologies. In patients with cancer and no signs of overt metastases sensitive
      methods have been developed to detect circulating tumor cells (CTCs) in the
      peripheral blood and disseminated tumor cells (DTCs) in the bone marrow. These
      technologies can be classified into cytometric and/or immunological and molecular
      approaches. Interestingly, the bone marrow seems to be a common homing tissue for
      cells derived from various epithelial tumors, and level 1a data from European and
      US groups have confirmed the prognostic impact of DTCs in the bone marrow of
      patients with breast cancer. Sequential peripheral blood analyses, however, are
      more convenient than bone marrow analyses for patients with solid tumors, and
      many research groups are currently assessing the clinical use of CTCs for
      assessment of prognosis and monitoring of systemic therapy. Molecular
      characterization of DTCs and CTCs opens a new avenue for understanding cancer
      dormancy, and might contribute to the identification of metastatic stem cells
      with important implications for future therapies. This Review focuses on the
      clinical relevance of the latest research results on blood-borne cancer
      micrometastases in patients with cancer.

PMID- 19399027
TI  - Short-circuiting regulatory T-cell proliferation during chronic infection.

PMID- 19399029
TI  - Temporal and spatial profiling of nuclei-associated proteins upon TNF-alpha/NF
      kappaB signaling.
AB  - The tumor necrosis factor (TNF)-alpha/NF-kappaB-signaling pathway plays a pivotal
      role in various processes including apoptosis, cellular differentiation, host
      defense, inflammation, autoimmunity and organogenesis. The complexity of the TNF
      alpha/NF-kappaB signaling is in part due to the dynamic protein behaviors of key
      players in this pathway. In this present work, a dynamic and global view of the
      signaling components in the nucleus at the early stages of TNF-alpha/NF-kappaB
      signaling was obtained in HEK293 cells, by a combination of subcellular
      fractionation and stable isotope labeling by amino acids in cell culture (SILAC).
      The dynamic profile patterns of 547 TNF-alpha-induced nuclei-associated proteins
      were quantified in our studies. The functional characters of all the profiles
      were further analyzed using that Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathway annotation. Additionally, many previously unknown effectors of TNF
      alpha/NF-kappaB signaling were identified, quantified and clustered into
      differential activation profiles. Interestingly, levels of Fanconi anemia group
      D2 protein (FANCD2), one of the Fanconi anemia family proteins, was found to be
      increased in the nucleus by SILAC quantitation upon TNF-alpha stimulation, which
      was further verified by western blotting and immunofluorescence analysis. This
      indicates that FANCD2 might be involved in TNF-alpha/NF-kappaB signaling through
      its accumulation in the nucleus. In summary, the combination of subcellular
      proteomics with quantitative analysis not only allowed for a dissection of the
      nuclear TNF-alpha/NF-kappaB-signaling pathway, but also provided a systematic
      strategy for monitoring temporal and spatial changes in cell signaling.

PMID- 19399028
TI  - Obesity, inflammation, and atherosclerosis.
AB  - Understanding of the pathophysiology of atherogenesis has evolved substantially
      during the last few decades. Atherosclerosis was once identified as a lipid
      storage disease, but is now recognized as a subacute inflammatory condition of
      the vessel wall, characterized by infiltration of macrophages and T cells, which
      interact with one another and with cells of the arterial wall. The pathological
      mechanisms of obesity recapitulate many features of the inflammatory processes at
      work in atherosclerosis. Our current appreciation of the similarities between
      obesity and atherosclerosis has already fostered innovations for the diagnosis,
      prognosis, and prevention of these two conditions.

PMID- 19399030
TI  - Systems biology unlimited.

PMID- 19399032
TI  - TMPRSS2-ERG and PTEN loss in prostate cancer.
AB  - Two studies show that the common recurrent gene fusion between TMPRSS2 and ERG
      promotes prostate cancer in both mouse and humans when PTEN is concurrently lost.
      In human prostate cancer, the presence of both these aberrations may be
      indicative of poor prognosis, suggesting that preclinical therapeutic research
      should target both of these pathways.

PMID- 19399033
TI  - X-cess of variants in XLMR.
AB  - A new study reports large-scale systematic resequencing of the coding exons of
      the X chromosome in males with X-linked mental retardation (XLMR), illustrating
      the challenge of sorting through large amounts of benign variation in order to
      identify disease-causing sequence changes.

PMID- 19399036
TI  - Editorial.
AB  - With this issue Optics Express begins Volume 5 of publication, and continues to
      set international standards for electronic publishing.

PMID- 19399034
TI  - Of flaky tails and itchy skin.
AB  - A new study defines the flaky tail mouse as a model for human atopic dermatitis
      caused by a null mutation in the gene encoding filaggrin, a key component of the
      epidermal barrier. Research in these mice will help explain how a disrupted
      barrier contributes to the pathogenesis of atopic dermatitis and to asthma
      arising in the context of atopic skin disease.

PMID- 19399037
TI  - Discussion to the angular aperture narrowing behavior inside AOTF crystal.
AB  - An off-perpendicular incident arrangement is suggested and tested in AOTF system
      design to improve the spectrum resolution and angular aperture. A special
      discussion is given to the "equivalent point design" of Si=56o where the optimum
      design parameters are reached.

PMID- 19399038
TI  - Observer performance for JPEG vs. Wavelet image compression of x-ray coronary
      angiograms.
AB  - Development of "filmless" cardiac catheterization laboratories is eminent. The
      problems of implementing a digital catheterization laboratory involve archiving
      large amounts of data per procedure and high transfer rates to retrieve previous
      procedures. Lossy compression can ccommodate these changes, but at the cost of
      possibly impairing detection of clinically important angiographic features. Our
      study involves the observer detection and classification of features in clinical
      images and the effects that JPEG and wavelet compression have on the
      detectability of these features. We found no significant degradation in human
      observer performance with 7:1 and 15:1 JPEG compressed images in 6 clinically
      relevant visual tasks. Human observer performance for wavelet compression
      degraded significantly for 2 out of 6 tasks at 7:1 compression and 4 out of 6
      tasks at 19:1 compression.

PMID- 19399039
TI  - Editorial.
AB  - Focus Issues: a Second Anniversary Note: Two years ago, in August 1997, we
      published 5 articles grouped under the heading "Mid-IR Laser Materials." These
      articles introduced Focus Issues into peer-reviewed science publishing. It seems
      to me that the Second Anniversary of that event merits notice and maybe a small
      celebration. Steven Bowman coordinated the first one, and since then we have
      published 25 other Focus Issues with 4-10 articles each, and other journals are
      beginning to try them. Focus Coordinators of future issues are certainly among
      the readers of this short note. I'll say more about that at the end, so read on.

PMID- 19399040
TI  - Interferometric nonlinear mixing in multiple-pass femtosecond optical parametric
      amplification.
AB  - We demonstrate that in multi-stage optical parametric amplifiers, spatial and
      temporal overlap of all products and pump on subsequent passes lead to strongly
      phase-dependent conversion, which has important consequences for output noise and
      beam profile characteristics. We verify a simple method to avoid this
      interferometric process.

PMID- 19399041
TI  - Introduction.
AB  - Several recent developments have resulted in considerable progress in the study
      of transverse effects and spatial mode dynamics in semiconductor lasers. Demands
      on higher and higher output powers have led to the development of wide-stripe
      lasers, coupled laser arrays, integrated master-oscillator power amplifiers
      (MOPAs), and other more complex laser structures for which spatial dependence of
      the laser mode becomes important. This is especially true for the vertical-cavity
      surface-emitting lasers (VCSELs), devices that have recently become commercially
      available and are being proposed for a multitude of interesting applications. In
      the case of a VCSEL, the transverse-mode behavior is inherently more complex
      compared with the traditional edge-emitting lasers because of a large Fresnel
      number associated with VCSELs. The recent interest in spatio-temporal dynamics of
      such lasers as an example of well-controlled, spatially extended, self-organizing
      systems has led to new understanding about patterns, defects, and other coherent
      and incoherent structures, all being important to large-aperture diode lasers.

PMID- 19399042
TI  - Journal of the Optical Society of America B Line-up.
AB  - Journal of the Optical Society of America B Line-up.

PMID- 19399043
TI  - Fourier-optical selection of higher order transverse modes in broad area lasers.
AB  - A partially and a highly antire ection coated broad area laser are operated in an
      external cavity Fourier-optical 4f set-up to experimentally investigate
      transverse mode selection. The external cavity consists of a lens and a spatial
      frequency filter. Running freely the lasers show non-stationary filamentation.
      Placing the spatial filter unit directly onto the optical axis gives cw
      fundamental mode operation and a transverse shift of the spatial filter in the
      plane of the active region allows for selective excitation of higher order modes.

PMID- 19399044
TI  - Transverse modes in oxide confined VCSELs: Influence of pump profile, spatial
      hole burning, and thermal effects.
AB  - We present experimental studies on the transverse mode emission behaviour of
      oxide-confined Vertical Cavity Surface Emitting Lasers (VCSELs). VCSELs with
      aperture diameters of 6um and 11um exhibit a wide variety of emission patterns
      from low order Hermite- Gaussian modes to high order Laguerre-Gaussian modes. We
      obtain detailed information about the spatial gain distribution by recording
      spontaneous emission intensity profiles during lasing operation. We conclude from
      these profiles, that the spatial carrier distribution is primarily governed by
      the in uence of pump induced current spreading and is only secondarily in uenced
      by further effects such as spatial hole burning, and thermal gradients in the
      laser. The combination of these mechanisms causes a strong tendency towards the
      emission of high order transverse modes.

PMID- 19399045
TI  - Stabilization of chaotic spatiotemporal filamentation in large broad area lasers
      by spatially structured optical feedback.
AB  - In large high-power broad-area lasers the spatiotemporal filamentation processes
      and instabilities occur macroscopic as well as on microscopic scales. Numerical
      simulations on the basis of Maxwell- Bloch equations for large longitudinally and
      transversely extended semiconductor lasers reveal the internal spatial and
      temporal processes, providing the relevant scales on which control for
      stabilization consequently has to occur. It is demonstrated that the combined
      longitudinal instabilities, filamentation, and propagation effects may be
      controlled by suitable spatially structured delayed optical feedback allowing, in
      particular, the control of coherent regimes in originally temporally and
      spatially chaotic states.

PMID- 19399046
TI  - Transverse mode dynamics of VCSELs through space-time domain simulation.
AB  - An approximation to the Maxwell-Semiconductor Bloch equations is used to model
      transverse mode dynamics of vertical-cavity surface-emitting lasers (VCSELs). The
      time-evolution of the spatial profiles of the laser field and carrier density is
      solved by a finite-difference algorithm. The algorithm is fairly general; it can
      handle devices of any shape, which are either gain or index guided or both. Also
      there is no a priori assumption about the type or number of modes. The physical
      modeling includes the nonlinear carrier dependence of the optical gain and
      refractive index and dispersion effects on the gain and the refractive index are
      also included.

PMID- 19399047
TI  - Editorial.
AB  - This issue of Optics Express takes advantage of the typical late summer slowdown
      in submissions. We are using the opportunity and the color graphics capabilities
      of Optics Express to announce and pre-publish three articles that are included in
      a forthcoming release in OSA's Classic Reprints on CD-ROM Series.

PMID- 19399048
TI  - Simulation of inferior mirages observed at the Halligen Sea.
AB  - Two unusual forms of inferior mirage are observed and photographed at the
      Halligen Sea. With heuristic analytic functions for the temperature profiles,
      numerical integration of the refraction differ-ential equation on a flat earth is
      performed. The simulation shows that a double inferior mirage can appear if a
      light wind carries hot air from above dry sandbanks in the mud flats. Horizontal
      stripes can appear in the mirage image if a water channel crosses the line of
      sight between the observer and the object.

PMID- 19399049
TI  - Laboratory experiments in atmospheric optics.
AB  - Old and new laboratory experiments on atmospheric optics with a focus on mirages,
      rainbows, and halos are presented. Some qualitative demonstrations serve
      primarily didactical purposes, e.g., by proving the existence of curved light
      rays in media with a gradient of the index of refraction, by directly visualizing
      the minimum-deviation curve for rainbow paths in water droplets, or by helping to
      elucidate the ray classes in hexagons that contribute to a specific halo. In
      addition, quantitative experiments allow a direct comparison of angular positions
      and intensities with analytical computations or Monte Carlo simulations of light
      scattering from small water droplets or ice hexagons. In particular, the latter
      can help us to understand complex halo phenomena.

PMID- 19399050
TI  - Effects of a butterfly scale microstructure on the iridescent color observed at
      different angles.
AB  - Multilayer thin-film structures in butterfly wing scales produce a colorful
      iridescence from reflected sunlight. Because of optical phenomena, changes in the
      angle of incidence of light and the viewing angle of an observer result in shifts
      in the color of butterfly wings. Colors ranging from green to purple, which are
      due to nonplanar specular reflection, can be observed on Papilio blumei
      iridescent scales. This refers to a phenomenon in which the curved surface
      patterns in the thin-film structure cause the specular component of the reflected
      light to be directed at various angles while affecting the spectral reflectivity
      at the same time by changing the optical path length through the structure. We
      determined the spectral reflectivities of P. blumei iridescent scales numerically
      by using models of a butterfly scale microstructure and experimentally by using a
      microscale-reflectance spectrometer. The numerical models accurately predict the
      shifts in spectral reflectivity observed experimentally.

PMID- 19399051
TI  - Coherence-manipulation of an atomic wave packet via electron-electron
      correlations.
AB  - An electronic wave packet is excited in the Rydberg states of atomic calcium. The
      strong excitation of the remaining valence electron modifies the particular
      coherent superposition state associated with this Rydberg wave packet due to the
      electron-electron correlation. This modification is observed by a coherent pump
      probe measurement in which the change of the global phase of the wave packet with
      respect to a local oscillator is found. The magnitude of the electron-electron
      correlation is varied experimentally and leads to sharp resonances in the phase.
      The coherence is maintained despite the open autoionization channel. The process
      also allows the manipulation of individual states within the wave packet.

PMID- 19399052
TI  - Analysis of imperfect polarizer effects in magnetic rotation spectroscopy.
AB  - Small amounts of ellipticity in the nominally linearly polarized light used in
      magnetic rotation spectroscopy play an important role in determining the
      character of the signals developed in these experiments. For example, ellipticity
      introduced by stress-induced birefringence can easily influence such signals more
      than does a nonzero polarizer extinction ratio. In addition, for nearly-crossed
      polarizers, an initial ellipticity allows one to probe magnetic circular
      dichroism instead of the more commonly investigated magnetic circular
      birefringence. A general expression for the magnetic rotation spectroscopy signal
      is derived and compared to experimental results. An expression for the detection
      sensitivity is developed by taking shot noise and rms laser power uctuations to
      be the dominant noise sources.

PMID- 19399053
TI  - Self-injection-locking of a CW-OPO by intracavity frequency-doubling the idler
      wave.
AB  - We report on the observation of self-injection-locking of the signal wave of an
      optical parametric oscillator (OPO) with the intracavity frequency doubled idler
      wave. The two-mirror OPO is based on a periodically poled LiNbO3 (PPLN) crystal
      and pumped with a grating stabilized, continuous-wave (CW) single-frequency diode
      master-oscillator power-amplifier (MOPA) system. Simultaneous quasi-phase
      matching (QPM) of OPO and second harmonic generation (SHG) is provided in the
      same crystal which carries two different domain gratings. The beat of the signal
      wave and the frequency-doubled idler wave is suppressed within a 500-kHz wide
      frequency range centered around zero as expected for self-injection- locking. The
      measurements prove the feasibility of optically phase-stabilized by-three
      division of an optical frequency with CW-OPOs using cascaded nonlinearities.

PMID- 19399054
TI  - Asymptotic light field in the presence of a bubble-layer.
AB  - We report that the submerged microbubbles are an efficient source of diffuse
      radiance and may contribute to a rapid transition to the diffuse asymptotic
      regime. In this asymptotic regime an average cosine is easily predictable and
      measurable.

PMID- 19399055
TI  - A new approach to compute overlap efficiency in axially pumped solid state
      lasers.
AB  - In this work, we are reporting a new approach to compute the overlap efficiency
      of end pumped solid-state laser systems. Unlike existing methods in which the
      overlap integral is computed with a linearize approximation near the threshold,
      in this method the inverse of the overlap integral is computed numerically in the
      above threshold regime for several values of circulating fields. Now by fitting a
      linear curve to this data the overlap efficiency is obtained. The effect of the
      beam quality factor is also taken into account. It is demonstrated that the
      linearized approximation near the threshold can give rise to 50% error in overlap
      efficiency. The method was used to estimate the overlap efficiency in different
      types of axially pumped lasers.

PMID- 19399056
TI  - Real-time SPIDER: ultrashort pulse characterization at 20 Hz.
AB  - We present an implementation of spectral phase interferometry for direct electric
      field reconstruction (SPIDER) which characterizes ultrashort optical pulses in
      the spectral or temporal domain at a rate of 20 Hz. This apparatus was used in
      real-time as a diagnostic tool to optimize our 1 kHz regeneratively amplified
      laser system for the shortest duration pulses.

PMID- 19399057
TI  - Magnetic-field effect in atomic ionization by intense laser fields.
AB  - Numerical integrations of the two-dimensional Schr"dinger equation that describes
      a flat atom interacting with an intense and linearly polarized laser field are
      presented. Simulations show the influence of the drift that is due to the
      magnetic field in situations in which a strong dichotomy of the wave function
      would otherwise have been expected.

PMID- 19399058
TI  - Pulse train characterisitcs of a passively Q-switched microchip laser.
AB  - A study of passively Q-switched microchip laser pulse trains yields approximate,
      yet reliable, formulae for the peak power, pulse energy, half-width, period, and
      the pulse shape in time. The pulse gain differential equation is made integrable
      by assuming that the laser absorption cross sections for the gain and saturable
      absorber are equal. We compare our predictions with an experiment which uses
      Nd:YAG as a gain medium and Cr:YAG as a saturable absorber. The agreement between
      theory and experiment for the period, pulse width, and the pulse energy is within
      10%.

PMID- 19399059
TI  - Cross-wavelength all-optical switching using nonlinearity of liquefying gallium.
AB  - The gallium/silica interface optical nonlinearity associated with a light-induced
      structural phase transition from a-gallium to a more reflective, more metallic
      phase shows an exceptionally broadband spectral response. It allows 40% deep
      nanosecond/microsecond cross-wavelength intensity modulation between signals at
      1.3 and 1.55aem.

PMID- 19399060
TI  - Broadband form birefringent quarter-wave plate for the mid-infrared wavelength
      region.
AB  - We discuss the design, fabrication and optical performance of a broadband form
      birefringent quarter-wave plate for the 3.5 to 5 aem wave-length region. Rigorous
      coupled wave analysis (RCWA) was used to design the requisite subwavelength
      grating for silicon substrates in ambient air. Fabricated samples yield a
      measured phase retardation of 89o to 102o over the desired wavelength range.

PMID- 19399061
TI  - Laser scanning third-harmonic-generation microscopy in biology.
AB  - A laser scanning microscope using third-harmonic generation as a probe is shown
      to produce high-resolution images of transparent biological specimens. Third
      harmonic light is generated by a tightly focused short-pulse laser beam and
      collected point-by-point to form a digital image. Demonstrations with two
      biological samples are presented. Live neurons in a cell culture are imaged with
      clear and detailed images, including organelles at the threshold of optical
      resolution. Internal organelles of yeast cells are also imaged, demonstrating the
      ability of the technique for cellular and intracellular imaging.

PMID- 19399062
TI  - Pulse simulations of a mirrored counterpropagating-QPM device.
AB  - A basic mirrored counterpropagating quasi-phase-matched device is studied with a
      pulsed input fundamental plane wave using the method of lines and the relaxation
      method. Several examples are given under varying spatial pulse length to device
      length ratios. An approximate upper bound on the device length is established
      from this study for practical pulsed applications; the largest usable length is
      approximately the same as the spatial length of the pulse.

PMID- 19399063
TI  - Instability of a mixed atom-molecule condensate under photoassociation.
AB  - Using the counterpart of the Gross-Pitaevskii equation, we study a system of
      atomic and molecular condensates in equilibrium in the presence of
      photoassociating light. All equilibria except a special case with only molecules
      are prone to an analog of the modulational instability in second-harmonic
      generation. The nature of the instability is such that the atoms and molecules
      aggregate in dense clumps.

PMID- 19399064
TI  - Enhanced optical transmission at the cutoff transition.
AB  - The phenomenon of extraordinary transmission in the optical regime for circular
      hole arrays in optically thick metal films is studied as a function of hole size
      and depth. In the limit of small holes compared to the depth, the transmission
      properties follow a waveguide type behavior. By describing the transmission
      process as resulting from the interference between a resonant and a non-resonant
      contribution, a transition is clearly revealed through the specific spectral
      variations of the resonance at a given hole depth. This transition is associated
      to a change in the attenuation through the hole as its size increases, and
      corresponds to the optimal condition for surface plasmon excitation.

PMID- 19399065
TI  - Waveguiding properties of a photonic crystal fiber with a solid core surrounded
      by four large air holes.
AB  - The polarization-dependent guiding properties of a hexagonal-lattice photonic
      crystal fiber with a solid-core surrounded by four large air holes are
      investigated. The appearance of a polarization dependent cutoff frequency,
      together with several parameters as the birefringence, the modal effective area,
      the group velocity dispersion and the polarization dependent loss are analyzed. A
      collection of fibers with different structural parameters were fabricated and
      characterized. An effective anti-guide structure from at least 450 nm to 1750 nm,
      a polarizing fiber with a polarization dependent loss of 16 dB/m at 1550 nm, and
      an endlessly singlemode polarization-maintaining fiber with group birefringence
      of 2.1x10(-3) at 1550 nm are reported. Experimental results are compared with
      accurate numerical modeling of the fibers.

PMID- 19399066
TI  - Enhanced light coupling in sub-wavelength single-mode silicon on insulator
      waveguides.
AB  - We report on NIR efficient end-coupling in single-mode silicon on insulator
      waveguides. Efficient coupling has been achieved using Polymer-Tipped Optical
      Fibers (PTOF) of adaptable radius of curvature (ROC). When compared with
      commercial micro lenses, systematic studies as a function of PTOF ROC, lead for
      subwavelength PTOF to a coupling factor enhancement as high as 2.5. This
      experimental behavior is clearly corroborated by radial FDTD simulations and an
      absolute coupling efficiency of about 50% is also estimated.

PMID- 19399067
TI  - Diode-pumped passively Q-switched Nd:Gd0.5Y0.5VO4 laser at 1.34 microm with
      V3+:YAG as the saturable absorber.
AB  - The performance of a diode-pumped passively Q-switched Nd:Gd(0.5)Y(0.5)VO(4)
      laser at 1.34 microm with V(3+):YAG as the saturable absorber was demonstrated
      for the first time to the best of our knowledge. The focal lengths of thermal
      lens in the diode-end-pumped Nd:Gd(0.5)Y(0.5)VO(4) laser for the 1.34 microm
      transition was experimentally investigated, with the corresponding proportion
      constant estimated to be approximately1.5x10(4) W/mm. For the passive Q-switching
      operation, the maximum average output power of 0.96 W was achieved under the pump
      power of 7.28 W, corresponding to optical-to-optical conversion and slope
      efficiency of 13.2% and 17.6%, respectively. The minimum pulse width attained was
      47.8 ns with the pulse repetition frequency of 76 kHz, with the single pulse
      energy and peak power estimated to be 8.7 microJ and 182 W, respectively.

PMID- 19399068
TI  - Comparing photonic band structure calculation methods for diamond and pyrochlore
      crystals.
AB  - The photonic band diagrams of close-packed colloidal diamond and pyrochlore
      structures, have been studied using Korringa-Kohn-Rostoker (KKR) and plane-wave
      calculations. In addition, the occurrence of a band gap has been investigated for
      the binary Laves structures and their constituent large- and small-sphere
      substructures. It was recently shown that these Laves structures give the
      possibility to fabricate the diamond and pyrochlore structures by self
      organization. The comparison of the two calculation methods opens the possibility
      to study the validity and the convergence of the results, which have been an
      issue for diamond-related structures in the past. The KKR calculations
      systematically give a lower value for the gap width than the plane-wave
      calculations. This difference can partly be ascribed to a convergence issue in
      the plane-wave code when a contact point of two spheres coincides with the grid.

PMID- 19399069
TI  - Polarization insensitive all-optical up-conversion for ROF systems based on
      parallel pump FWM in a SOA.
AB  - We have proposed and experimentally investigated polarization insensitive all
      optical up-conversion for ROF system based on FWM in a semiconductor optical
      amplifier (SOA). The parallel pump is generated based on odd-order optical
      sidebands and carrier suppression using an external intensity modulator and a
      cascaded optical filter. Therefore, the two pumps are always parallel and phase
      locked, which makes system polarization insensitive. After FWM in a SOA and
      optical filtering, similar to single sideband (SSB) 40 GHz optical millimeter
      wave is generated only using 10 GHz RF as local oscillator (LO). The receiver
      sensitivity at a BER of 10(-9) for the up-converted signals is -28.4 dBm. The
      power penalty for the up-converted downstream signals is smaller than 1 dBm after
      20 km SSMF-28 transmission.

PMID- 19399070
TI  - A diode side-pumped KTiOAsO4 Raman laser.
AB  - A KTiOAsO(4) Raman laser is realized within a diode side-pumped acousto-optically
      Q-switched Nd:YAG laser. Efficient nanosecond first-Stokes generations at 1091.4
      nm are obtained with three 30-mm-long KTA crystals. Under an incident diode power
      of 60.9 W and a pulse repetition rate of 4 kHz, a first-Stokes power of 4.55 W is
      obtained, corresponding to a diode-to-Stokes conversion efficiency of 7.5%. The
      single pulse energy is up to 1.14 mJ and the peak power is 18.0 kW.

PMID- 19399071
TI  - Controllable transport mean free path of light in xerogel matrixes embedded with
      polystyrene spheres.
AB  - Xerogel matrices, made by sol-gel techniques, are embedded with polystyrene
      spheres to promote multiple scattering of light. Varying the concentration of the
      spheres inside the matrix allows one to adjust the transport mean free path of
      light inside the material. Coherent backscattering measurements show that a range
      of transport mean free paths from 90 to 600 nm is easily achieved. The
      determination of the matrix refractive index permits a direct comparison to
      multiple scattering and Mie theory. Such tunable diffusive sol-gel derived
      samples can be further optimized as random laser materials.

PMID- 19399072
TI  - Novel grating design approach by radiation modes coupling in nonlinear optical
      waveguides.
AB  - In integrated optics the radiation modes represent a negative aspect regarding
      the propagation of guided modes. They characterize the losses of the substrate
      region but can contribute to enhance the guided modes by considering the coupling
      through properly designed gratings arranged at the core/substrate interface. By
      tailored gratings, the radiation modes become propagating modes and increase the
      guided power inside the waveguide guiding region. This enhancement is useful
      especially in low intensity processes such as second harmonic chi(2) conversion
      process. For this purpose, we analyze accurately the radiation modes contribution
      in a chi(2) GaAs/AlGaAs nonlinear waveguide where second harmonic signal is
      characterized by a low power intensity. This analysis considers a new design
      approach of multiple grating which enhances a fundamental guided mode at
      lambda(FU) =1.55 microm and a codirectional second harmonic guided mode at
      lambda(SH) =0.775 microm. In particular we analyze the second harmonic conversion
      efficiency by studying the coupling effect of three gratings. The combined
      effects of the gratings provide an efficient second harmonic field conversion.
      Design considerations, based on the coupled mode equations analysis, are
      theoretically discussed. A good agreement between analytical and numerical
      results is observed.

PMID- 19399073
TI  - Reduction of double Rayleigh scattering noise in distributed Raman amplifiers
      employing higher-order pumping.
AB  - We present a theoretical study of the performance of distributed Raman amplifiers
      with higher order pumping schemes, focusing in particular on double Rayleigh
      scattering (DRS) noise. Results show an unexpected significant DRS noise
      reduction for pumping order higher than third, allowing for an overall
      performance improvement of carefully designed distributed amplifiers, ensuring a
      large optical signal-to-noise ratio improvement together with reduced DRS-induced
      penalties.

PMID- 19399074
TI  - 1 micros tunable delay using parametric mixing and optical phase conjugation in
      Si waveguides.
AB  - We demonstrate continuously tunable optical delays as large as 1.1 micros range
      for 10 Gb/s NRZ optical signals based on four-wave mixing (FWM) process in
      silicon waveguide. The large delay range is made possible by a novel wavelength
      optimized optical phase conjugation scheme, which allows for tunable dispersion
      compensation to minimize the residual group-velocity dispersion (GVD) for the
      entire tuning range.

PMID- 19399075
TI  - Analysis of the temporal coherence function of a femtosecond optical frequency
      comb.
AB  - The temporal coherence function of the femtosecond pulse train from femtosecond
      optical frequency comb (FOFC) has been studied. The theoretical derivation, which
      is based on the electric field equations of a pulse train, has been used to model
      the temporal coherence function of the FOFC and shows good agreement with
      experimental measurements which are taken with a modified Michelson
      interferometer. The theoretical and experimental points of view provide useful
      information for applications of FOFC in imaging and metrology.

PMID- 19399076
TI  - Active control and spatial mapping of mid-infrared propagating surface plasmons.
AB  - Periodic arrays of subwavelength apertures in metal films have been shown to
      exhibit strongly enhanced transmission at wavelengths determined by the
      periodicity of the film as well as the optical properties of the metal and
      surrounding dielectric material. Here we investigate the coupling between such a
      grating and a Quantum Cascade Laser. By actively tuning the optical properties of
      our grating, we control the coupling of laser light to the plasmonic structure,
      switching our grating from a predominantly transmitting state to a state that
      allows coupling to propagating surface waves, which can then be imaged on the
      metallic surface.

PMID- 19399077
TI  - Practical methods for retrace error correction in nonnull aspheric testing.
AB  - Nonnull test is often adopted for aspheric testing. But due to its violation of
      null condition, the testing rays will follow different paths from the reference
      and aberrations from the interferometer will not cancel out, leading to widely
      difference between the obtained surface figure and that of the real, which is
      called the Retrace-error accordingly. In this paper, retrace error of nonnull
      aspheric testing is analyzed in detail with conclusions that retrace error has
      much to do with the aperture, F number and surface shape error of the aspheric
      under test. Correcting methods are proposed according to the manner of the
      retrace errors. Both computer simulation and experimental results show that the
      proposed methods can correct the retrace error effectively. The analysis and
      proposed correction methods bring much to the application of nonnull aspheric
      testing.

PMID- 19399078
TI  - Room temperature continuous wave operation of InAs/GaAs quantum dot photonic
      crystal nanocavity laser on silicon substrate.
AB  - Room temperature, continuous-wave lasing in a quantum dot photonic crystal
      nanocavity on a Si substrate has been demonstrated by optical pumping. The laser
      was an air-bridge structure of a two-dimensional photonic crystal GaAs slab with
      InAs quantum dots inside on a Si substrate fabricated through wafer bonding and
      layer transfer. This surface-emitting laser exhibited emission at 1.3 microm with
      a threshold absorbed power of 2 microW, the lowest out of any type of lasers on
      silicon.

PMID- 19399079
TI  - Performance influence of carrier absorption to the Mach-Zehnder-interference
      based silicon optical switches.
AB  - The free carrier absorption effect in silicon modulation is a detrimental
      behavior that can influence the crosstalk of interference-based optical switches.
      Based on the experimental analysis of a 2x2 p-i-n silicon switch, we give a
      conservative estimate of the crosstalk ability of Mach-Zehnder optical switches.
      Experimental result shows that, while using a 1475 microm-long phase shifter, the
      loss penalty almost reaches 1.45 dB/pi, which deteriorates the most ideal
      crosstalk to just 30 dB. The possible solutions to overcome this limitation are
      also discussed at the cost of the other device performance.

PMID- 19399080
TI  - Spatiotemporal pulse-train solitons.
AB  - We propose spatiotemporal solitons that consist of trains of short pulses. The
      pulses are collectively trapped in the transverse directions by a slow
      nonlinearity and each pulse is self-trapped in the longitudinal direction by a
      fast nonlinearity. We demonstrate numerically spatiotemporal bright pulse-train
      solitons (trains of light bullets) and temporally-dark spatiotemporal pulse-train
      solitons in an experimentally feasible scheme.

PMID- 19399081
TI  - Polarized micro-cavity organic light-emitting devices.
AB  - We present the results of a study of light emissions from a polarized micro
      cavity Organic Light-Emitting Device (OLED), which consisted of a flexible,
      anisotropic one-dimensional (1-D) photonic crystal (PC) film substrate. It is
      shown that luminous Electroluminescent (EL) emissions from the polarized micro
      cavity OLED were produced at relatively low operating voltages. It was also found
      that the peak wavelengths of the emitted EL light corresponded to the two split
      eigen modes of the high-energy band edges of the anisotropic PC film, with a
      strong dependence on the polarization state of the emitting light. For
      polarization along the ordinary axis of the anisotropic PC film, the optical
      split micro-cavity modes occurred at the longer high-energy photonic band gap
      (PBG) edge, while for polarization along the extraordinary axis, the split micro
      cavity modes occurred at the shorter high-energy PBG edge, with narrow
      bandwidths. We demonstrated that the polarization and emission mode of the micro
      cavity OLED may be selected by choosing the appropriate optical axis of the
      anisotropic 1-D PC film.

PMID- 19399082
TI  - Rainbow-like radiation from an omni-directional source placed in a uniaxial
      metamaterial slab.
AB  - In this paper, the radiation of an omni-directional line source placed in a
      uniaxial metamaterial slab is experimentally presented. The anisotropic slab made
      of metallic symmetrical rings with dispersive permeability is investigated both
      theoretically and experimentally. For low value of the permeability, a directive
      radiation at the broadside of the slab can be obtained. Due to the excitation of
      the leaky wave mode supported by this structure, the emitted electromagnetic wave
      transmits at a greater angle from the normal of the slab as the value of
      permeability increases along with the frequency. Thus a rainbow-like radiation
      will be formed since waves of different frequencies will deflect into different
      directions.

PMID- 19399083
TI  - Nonlinear pulse compression of picosecond parabolic-like pulses synthesized with
      a long period fiber grating filter.
AB  - tract: We demonstrate high quality pulse compression at high repetition rates by
      use of spectral broadening of short parabolic-like pulses in a normally
      dispersive highly nonlinear fiber (HNLF) followed by linear dispersion
      compensation with a conventional SMF-28 fiber. The key contribution of this work
      is on the use of a simple and efficient long-period fiber grating (LPFG) filter
      for synthesizing the desired parabolic-like pulses from sech(2)-like input
      optical pulses; this all-fiber low-loss filter enables reducing significantly the
      required input pulse power as compared with the use of previous all-fiber pulse
      re-shaping solutions (e.g. fiber Bragg gratings). A detailed numerical analysis
      has been performed in order to optimize the system's performance, including
      investigation of the optimal initial pulse shape to be launched into the HNLF
      fiber. We found that the pulse shape launched into the HNLF is critically
      important for suppressing the undesired wave breaking in the nonlinear spectral
      broadening process. The optimal shape is found to be independent on the
      parameters of normally dispersive HNLFs. In our experiments, 1.5-ps pulses
      emitted by a 10-GHz mode-locked laser are first reshaped into 3.2-ps parabolic
      like pulses using our LPFG-based pulse reshaper. Flat spectrum broadening of the
      amplified initial parabolic-like pulses has been generated using propagation
      through a commercially-available HNLF. Pulses of 260 fs duration with satellite
      peak and pedestal suppression greater than 17 dB have been obtained after the
      linear dispersion compensation fiber. The generated pulses exhibit a 20-nm wide
      supercontinuum energy spectrum that has almost a square-like spectral profile
      with >85% of the pulse energy contained in its FWHM spectral bandwidth.

PMID- 19399084
TI  - Polarizer-free, electrically switchable and optically rewritable displays based
      on dye-doped polymer-dispersed liquid crystals.
AB  - This work demonstrates the feasibility of a polarizer-free, electrically
      switchable and optically rewritable display based on dye-doped polymer-dispersed
      liquid crystals (DD-PDLCs). Experimental results indicate that the doped dyes are
      homeotropically adsorbed onto the polymer film when an appropriate AC voltage is
      applied during patterning. The adsorbed dyes in the illuminated region then align
      the liquid crystals homeotropically, and produce a transparent pattern in the
      scattering background without any polarizer. Notably, the adsorbed dyes can be
      erased and readsorbed using thermal and optical treatments, respectively. The
      switching time of the fabricated display is of the order of milliseconds, and the
      contrast ratio is approximately 30.

PMID- 19399085
TI  - Highly dispersive slot waveguides.
AB  - We propose a slot-waveguide with high dispersion, in which a slot waveguide is
      coupled to a strip waveguide. A negative dispersion of up to -181520 ps/nm/km is
      obtained due to a strong interaction of the slot and strip modes. A flat and
      large dispersion is achievable by cascading the dispersive slot-waveguides with
      varied waveguide thickness or width for dispersion compensation and signal
      processing applications. We show - 31300 ps/nm/km dispersion over 147-nm
      bandwidth with <1% variance.

PMID- 19399086
TI  - Cherenkov phase matched THz-wave generation with surfing configuration for bulk
      lithium nobate crystal.
AB  - We demonstrated a Cherenkov phase matched THz-wave generation with surfing
      configuration for bulk lithium niobate crystal. THz-wave output was enhanced
      about 50 times by suppressing phase mismatching for THz-wave propagation
      direction. The suppression was achieved by combining two pumping waves with dual
      wavelength with finite angle, and THz-frequency was controllable by changing the
      angle within 2.5 degrees range. Higher frequency THz-wave generation at around
      4.0 THz was successfully obtained by the method.

PMID- 19399087
TI  - Time-resolved pump-probe technology with phase object for measurements of optical
      nonlinearities.
AB  - A new time-resolved pump-probe system with phase object, which is based on the PO
      Z-scan technique and the standard pump-probe system, is presented. This new
      method can simultaneously investigate the dynamic of nonlinear absorption and
      refraction conveniently. On the other hand, both degenerate and nondegenerate
      pump and probe beams in any polarization states can be used in this system. The
      nonlinear optical properties of tetrasulfonated copper phthalocyanine dissolved
      in dimethyl sulfoxide solution are investigated by using this system.

PMID- 19399088
TI  - Active plasmonic devices via electron spin.
AB  - A class of active terahertz devices that operate via particle plasmon
      oscillations is introduced for ensembles consisting of ferromagnetic and
      dielectric micro-particles. By utilizing an interplay between spin-orbit
      interaction manifesting as anisotropic magnetoresistance and the optical distance
      between ferromagnetic particles, a multifaceted paradigm for device design is
      demonstrated. Here, the phase accumulation of terahertz radiation across the
      device is actively modulated via the application of an external magnetic field.
      An active plasmonic directional router and an active plasmonic cylindrical lens
      are theoretically explored using both an empirical approach and finite-difference
      time-domain calculations. These findings are experimentally supported.

PMID- 19399089
TI  - High speed liquid crystal over silicon display based on the flexoelectro-optic
      effect.
AB  - One of the key technologies to evolve in the displays market in recent years is
      liquid crystal over silicon (LCOS) microdisplays. Traditional LCOS devices and
      applications such as rear projection televisions, have been based on intensity
      modulation electro-optical effects, however, recent developments have shown that
      multi-level phase modulation from these devices is extremely sought after for
      applications such as holographic projectors, optical correlators and adaptive
      optics. Here, we propose alternative device geometry based on the flexoelectric
      optic effect in a chiral nematic liquid crystal. This device is capable of
      delivering a multilevel phase shift at response times less than 100 microsec
      which has been verified by phase shift interferometry using an LCOS test device.
      The flexoelectric on silicon device, due to its remarkable characteristics,
      enables the next generation of holographic devices to be realized.

PMID- 19399090
TI  - Intense red light emission of Eu3+-doped LiGd(PO3)4 for mercury-free lamps and
      plasma display panels application.
AB  - In order to obtain a suitable red phosphor for mercury-free lamps and plasma
      display panels (PDPs), samples of trivalent europium-activated polyphosphate
      LiGd(PO(3))(4):Eu(3+) (LGP:Eu(3+)) were prepared by a solid-state reaction
      technique at high temperature. The vacuum ultraviolet (VUV)-visible spectroscopic
      properties were investigated. Because the phosphor LiGd(1-x)Eu(x)(PO(3))(4) for x
      = 0.50 shows broad and strong absorption in VUV region and exhibits intensive
      emission under 147/172 nm excitation in comparison with the PDP commercial red
      phosphor (Y, Gd)BO(3):Eu(3+), it is considered to be a promising red phosphor for
      mercury-free lamps and plasma display panels application.

PMID- 19399091
TI  - Ultra-compact photonic crystal based polarization rotator.
AB  - An asymmetrically loaded photonic crystal based polarization rotator has been
      introduced, designed and simulated. The polarization rotator structure consists
      of a single defect line photonic crystal slab waveguide with asymmetrically
      etched upper layer. To continue the rotation from a given input polarization to
      the desired output polarization the upper layer is alternated on either side of
      the defect line, periodically. Coupled mode theory based on semi-vectorial modes
      and plane wave expansion methods are employed to design the polarization rotator
      structure around a particular frequency band of interest. The 3D-FDTD simulation
      results agree with the coupled mode analysis around the region of interest
      specified during the design. Complete polarization rotation is achieved over the
      propagation length of 12lambda. For this length, the coupling efficiency higher
      than 90% is achieved within the normalized frequency band of 0.258-0.262.

PMID- 19399092
TI  - Temperature dependence of a diode-pumped cryogenic Er:YAG laser.
AB  - We report the laser performance of resonantly diode-pumped Er:YAG from liquid
      nitrogen temperature to above room temperature. Relative to incident pump power,
      the best performance was observed at approximately 160 K. Spectroscopy and
      modeling show that this is due primarily to the changing efficiency of diode pump
      absorption as the absorption lines broaden with temperature. However, the physics
      of the Er:YAG system indicates that even with arbitrarily narrow pump linewidth
      the most efficient laser performance should occur at a temperature somewhat above
      77 K. The causes of the temperature dependence are at least qualitatively
      understood.

PMID- 19399093
TI  - Evanescent modes in out-of-plane band structure for two-dimensional photonic
      crystals.
AB  - Reflection, diffraction and transmission of optical waves at the interface
      between a photonic crystal and the surrounding air can be described by
      propagating and evanescent Bloch modes. We have found such modes for one of the
      canonical two-dimensional photonic crystals, identical circular cylinders in a
      square pattern. We present computed out-of-plane band diagrams for propagating as
      well as evanescent modes, obtained with a numerical method based on Fourier
      Bessel expansions. For a given frequency, all the modes are evanescent, except
      for a few low-order propagating modes. We find that most of the evanescent modes
      have a purely imaginary z-component of the Bloch wave vector, but many of the
      modes have a complex z-component.

PMID- 19399094
TI  - Calibration and testing with real turbulence of a pyramid sensor employing static
      modulation.
AB  - The pyramid sensor (PS) is an interesting alternative to the Shack-Hartmann
      wavefront sensor (SH WFS) for astronomical Adaptive Optics (AO) because of its
      potential advantages in sensitivity and applicability to novel wavefront sensing
      schemes. The PS uses a pyramidal prism to perform a knife-edge test in two
      dimensions simultaneously and relies on modulating the position of the prism to
      increase the linear dynamic range. It has been suggested that this could also be
      accomplished by a static diffusing element. We test this idea and show that the
      diffuser produces a modulation effect. We compare the results of our PS to a SH
      WFS measuring spatial and temporal properties of real turbulence produced in the
      lab with a hot-air turbulence generator.

PMID- 19399095
TI  - Optical microfiber coil delay line.
AB  - The feasibility of a broadband, miniature, and low loss optical delay line
      composed of a coiled microfiber with several-micron radius is demonstrated
      theoretically. Under the introduced low-loss condition, the fundamental mode of
      the microfiber is shifted away and does not scatter from the interfaces with the
      central rod and adjacent turns. Dimensions of the designed 100 ns feedforward
      microfiber delay line containing 20 m of microfiber are 5 mm x 5 mm x 20 mm at
      the radiation wavelength 1.5 microm and can be much smaller for the recirculating
      loop delay line. These dimensions can be further optimized by varying the radii
      of the microfiber and coil. The predicted insertion loss of this device is
      approximately 0.004 dB/ns, which is two orders of magnitude smaller than the loss
      achieved presently for the miniature delay lines. A curved microfiber taper is
      proposed as a compact, low-loss, and broadband connection to this optical delay
      line. The taper adiabatically converts the input fundamental mode of a straight
      microfiber into the shifted mode of the coiled microfiber.

PMID- 19399096
TI  - Enhanced third-order nonlinear effects in slow-light photonic-crystal slab
      waveguides of line-defect.
AB  - We experimentally studied enhancement of the third-order nonlinear optical
      phenomena, i.e., self-phase modulation due to optical Kerr effect and two-photon
      absorption (TPA) in a small group-velocity (V(g)) line-defect guided-mode of
      AlGaAs-based photonic-crystal slab waveguide. We found that the phase shift
      Deltaphi or nominal Kerr constant n'(2) and TPA coefficient beta were strikingly
      enhanced due to small V(g) as the band edge was approached, such that they were
      proportional to (V(g))(-2); the nonlinear refractive index n(2) is enhanced
      proportional to V(g)(-1). We also observed that owing to this enhancement as well
      as an extremely small cross-section area, the energy required for inducing pi
      phase shift was very small, being of an order of a few pJ for 5 ps optical pulse
      and for a 0.5-mm long sample. Based on those results, we discuss the possibility
      of developing ultra-fast and ultra-small all-optical switches that operate due to
      cross-phase modulation.

PMID- 19399097
TI  - Photonic measurement of microwave frequency based on phase modulation.
AB  - A photonic approach for microwave frequency measurement is proposed. In this
      approach, an optical carrier is modulated by an unknown microwave signal through
      a phase modulator. The modulated optical signal is then split into two parts; one
      part passes through a spool of polarization maintaining fiber (PMF) and the other
      one, through a dispersion compensation fiber (DCF), to introduce different
      microwave power penalties. After the microwave powers of the two parts are
      measured by two photodetectors, a fixed frequency-to-power mapping is established
      by obtaining an amplitude comparison function (ACF). A proof-of-concept
      experiment demonstrates frequency measurement over a range of 10.5 GHz, with
      measurement error less than +/-0.07 GHz.

PMID- 19399098
TI  - High-energy wave-breaking-free pulse from all-fiber mode-locked laser system.
AB  - We demonstrated an all-fiber mode-locked laser system which generated high-energy
      wave-breaking-free pulses with low repetition rate. The system included a
      passively mode-locked fiber laser which acted as a master oscillator and an Yb
      doped fiber amplifier. By increasing the cavity length of the laser, pulse energy
      could be significantly increased. According to different cavity length, wave
      breaking-free pulse with 2.9 nJ-6.9 nJ pulse energy and 870 kHz-187 kHz
      repetition rate has been achieved from the master oscillator. Over 4 microJ pulse
      can be obtained after amplification.

PMID- 19399099
TI  - Efficient unidirectional ridge excitation of surface plasmons.
AB  - Using leakage-radiation microscopy, we characterize the efficiency of
      unidirectional surface-plasmon excitation with periodic (800 nm) arrays of 130-nm
      high and 330-nm-wide gold ridges on a thin gold film illuminated with a focused
      (5-microm-wide) laser beam. We demonstrate that, at the resonant wavelength of
      816 nm, the excitation efficiency of > 0.4 can be obtained with >or= 5 ridges by
      adjusting the beam position. Conducting numerical simulations, we account for the
      experimental results and calculate the electric-field enhancement achieved near
      the gold surface.

PMID- 19399100
TI  - Multiplexed broadband beam steering system utilizing high speed MEMS mirrors.
AB  - We present a beam steering system based on micro-electromechanical systems
      technology that features high speed steering of multiple laser beams over a broad
      wavelength range. By utilizing high speed micromirrors with a broadband metallic
      coating, our system has the flexibility to simultaneously incorporate a wide
      range of wavelengths and multiple beams. We demonstrate reconfiguration of two
      independent beams at different wavelengths (780 and 635 nm) across a common 5x5
      array with 4 micros settling time. Full simulation of the optical system provides
      insights on the scalability of the system. Such a system can provide a versatile
      tool for applications where fast laser multiplexing is necessary.

PMID- 19399101
TI  - A prototype hybrid intraoperative probe for ovarian cancer detection.
AB  - A novel prototype intraoperative system combining positron detection and optical
      coherence tomography (OCT) imaging has been developed for early ovarian cancer
      detection. The probe employs eight plastic scintillating fiber tips for
      preferential detection of local positron activity surrounding a central scanning
      OCT fiber providing volumetric imaging of tissue structure in regions of high
      radiotracer uptake. Characterization measurements of positron sensitivity,
      spatial response, and position mapping are presented for Tl(204)/Cs(137) sources
      as well as 18F-FDG. In conjunction with co-registered frequency domain OCT
      measurements the results demonstrate the potential for a miniaturized
      laparoscopic probe offering simultaneous functional localization and structural
      imaging for improved early cancer detection.

PMID- 19399102
TI  - Real-time liquid-crystal atmosphere turbulence simulator with graphic processing
      unit.
AB  - To generate time-evolving atmosphere turbulence in real time, a phase-generating
      method for our liquid-crystal (LC) atmosphere turbulence simulator (ATS) is
      derived based on the Fourier series (FS) method. A real matrix expression for
      generating turbulence phases is given and calculated with a graphic processing
      unit (GPU), the GeForce 8800 Ultra. A liquid crystal on silicon (LCOS) with
      256x256 pixels is used as the turbulence simulator. The total time to generate a
      turbulence phase is about 7.8 ms for calculation and readout with the GPU. A
      parallel processing method of calculating and sending a picture to the LCOS is
      used to improve the simulating speed of our LC ATS. Therefore, the real-time
      turbulence phase-generation frequency of our LC ATS is up to 128 Hz. To our
      knowledge, it is the highest speed used to generate a turbulence phase in real
      time.

PMID- 19399103
TI  - Fourier factorization with complex polarization bases in modeling optics of
      discontinuous bi-periodic structures.
AB  - The coupled wave theory dealing with optics of discontinuous two-dimensional (2D)
      periodic structures is reformulated by using Fourier factorization with complex
      polarization bases, which is a generalized implementation of the fast Fourier
      factorization rules. The modified approach yields considerably improved
      convergence properties, as shown on an example of a 2D quartz grating. The method
      can also be applied to the calculation of 2D photonic band structures or
      nonperiodic cylindrical devices, and can be generalized to elements with
      arbitrary cross-sections.

PMID- 19399104
TI  - Lasing from dye-doped icosahedral quasicrystals in dichromate gelatin emulsions.
AB  - Lasing requires an active gain medium and a feedback mechanism. In conventional
      lasers the feedback is provided externally, e.g. by mirrors. An alternate
      approach is through Bloch waves in photonic crystals composed of periodic
      dielectric materials in which propagation of light in certain frequency ranges,
      known as photonic bandgaps, is forbidden. Compared to periodic crystals,
      quasicrystals have higher symmetry and are more favorable for the formation of
      photonic bandgaps. Hence quasicrystals are more efficient in providing the
      feedback mechanism for lasing. Here we report observation of lasing at visible
      wavelengths from dye-doped three-dimensional icosahedral quasicrystals fabricated
      in dichromate gelatin emulsions using a novel seven-beam optical interference
      holographic method. Multi-directional lasing exhibiting the icosahedral symmetry
      was observed. The lasing modes and pattern were explained by using the lasing
      condition expressed in the reciprocal lattice space of the icosahedral
      quasicrystal.

PMID- 19399105
TI  - Noninvasive monitoring of cerebral blood oxygenation in ovine superior sagittal
      sinus with novel multi-wavelength optoacoustic system.
AB  - Noninvasive monitoring of cerebral blood oxygenation with an optoacoustic
      technique offers advantages over current invasive and noninvasive methods. We
      report the results of in vivo studies in the sheep superior sagittal sinus (SSS),
      a large central cerebral vein. We changed blood oxygenation by increasing and
      decreasing the inspired fraction of oxygen (FiO(2)). Optoacoustic measurements
      from the SSS were performed at wavelengths of 700, 800, and 1064 nm using an
      optical parametric oscillator as a source of pulsed near-infrared light. Actual
      oxygenation of SSS blood was measured with a CO-Oximeter in blood samples drawn
      from the SSS through a small craniotomy. The amplitude of the optoacoustic signal
      induced in the SSS blood at lambda = 1064 nm closely followed the changes in
      blood oxygenation, at lambda = 800 nm was almost constant, and at lambda = 700 nm
      was changing in the opposite direction, all in accordance with the absorption
      spectra of oxy- and deoxyhemoglobin. The optoacoustically predicted oxygenation
      correlated well with actual blood oxygenation in sheep SSS (R(2) = 0.965 to
      0.990). The accuracy was excellent, with a mean difference of 4.8% to 9.3% and a
      standard deviation of 2.8% to 4.2%. To the best of our knowledge, this paper
      reports for the first time accurate measurements of cerebral venous blood
      oxygenation validated against the "gold standard" CO-Oximetry method.

PMID- 19399106
TI  - Slot-waveguide cavities for optical quantum information applications.
AB  - To take existing quantum optical experiments and devices into a more practical
      regimes requires the construction of robust, solid-state implementations. In
      particular, to observe the strong-coupling regime of tom-photon interactions
      requires very small cavities and large quality factors. Here we show that the
      slot-waveguide geometry recently introduced for photonic applications is also
      promising for quantum optical applications in the visible regime. We study
      diamond- and GaP-based slot-waveguide cavities (SWCs) compatible with diamond
      colour centres e.g. nitrogen-vacancy (NV) defect. We show that one can achieve
      increased single-photon Rabi frequencies of order O(10(11)) rad s(-1) in ultra
      small cavity modal volumes, nearly 2 orders of magnitude smaller than previously
      studied diamond-based photonic crystal cavities.

PMID- 19399107
TI  - Broadband tunable optical parametric amplification from a single 50 MHz ultrafast
      fiber laser.
AB  - We have demonstrated a 0.7 microm - 1.9 microm wavelength-tunable light source
      based on a single-pass optical parametric amplification (OPA) in a multiperiod
      magnesium oxide-doped periodically poled lithium niobate crystal. The OPA pump
      was a frequency-doubled ultrafast ytterbium-doped fiber oscillator, and the
      residual 1040 nm laser power after frequency doubling was recycled to generate a
      supercontinuum seeding source. Compared with conventional OPAs, this system is
      free from timing jitter between the pump laser and the seeding source. Over 50%
      conversion efficiency was obtained with 10 nJ pump energy. Combined with a 50 MHz
      repetition rate, this versatile source is ideal for biomedical and spectroscopic
      applications.

PMID- 19399108
TI  - Effects of astigmatism on spectra, coherence and polarization of stochastic
      electromagnetic beams passing through an astigmatic optical system.
AB  - Analytical formulas for the cross-spectral density matrix of stochastic
      electromagnetic Gaussian Schell-model (EGSM) beams passing through an astigmatic
      optical system are derived. We show both analytically and by numerical examples
      the effects of astigmatism on spectra, coherence and polarization of stochastic
      electromagnetic EGSM beams propagating through an astigmatic lens. A comparison
      with the aberration-free case is made, and shows that the astigmatism has
      significant effect on the spectra, coherence and polarization.

PMID- 19399109
TI  - Correct definition of the Poynting vector in electrically and magnetically
      polarizable medium reveals that negative refraction is impossible: comment.
AB  - It is shown that, when all macroscopic currents associated with the electric and
      magnetic polarizability are properly accounted for, the standard expression for
      the Poynting vector and the average work exerted by the electric field on the
      electric charges provide exactly the same value for the heating rate. Therefore,
      there is no contradiction between negative refraction and thermodynamics.

PMID- 19399111
TI  - The use of pulse synthesis for optimization of photoacoustic measurements.
AB  - In this paper the use of pulse shaping in photoacoustic (PA) measurements is
      presented. The benefits of this approach are demonstrated by utilizing it for
      optimization of either the responsivity or the sensitivity of PA measurements.
      The optimization is based on the observation that the temporal properties of the
      PA effect can be represented as a linear system which can be fully characterized
      by its impulse response. Accordingly, the response of the PA system to an input
      optical pulse, whose instantaneous power is arbitrarily shaped, can be
      analytically predicted via a convolution between the pulse envelope and the PA
      impulse response. Additionally, the same formalism can be used to show that the
      response of the PA system to a pulse whose instantaneous power is a reversed
      version of the impulse response, i.e. a matched pulse, would exhibit optimal peak
      amplitude when compared with all other pulses with the same energy. Pulses can
      also be designed to optimize the sensitivity of the measurement to a variation in
      a specific system parameter. The use of the matched pulses can improve SNR and
      enable a reduction in the total optical energy required for obtaining a
      detectable signal. This may be important for applications where the optical power
      is restricted or for dynamical measurements where long integration times are
      prohibited. To implement this new approach, a novel PA optical setup which
      enabled synthesis of excitation waveforms with arbitrary temporal envelopes was
      constructed. The setup was based on a tunable laser source, operating in the near
      IR range, and an external electro-optic modulator. Using this setup, our approach
      for system characterization and response prediction was tested and the
      superiority of the matched pulses over other common types of pulses of equal
      energy was demonstrated.

PMID- 19399112
TI  - On illumination schemes for wide-field CARS microscopy.
AB  - New system for a wide-field CARS microscopy is demonstrated, including two
      schemes of non-phase-matching illumination. Several advantages including high
      Stokes pulse energy, pulse-to-pulse stability and inherent synchronization
      between pump and Stokes pulses were brought by use of methane-filled Raman
      converter. Spatial resolution of the system with axially symmetric illumination,
      0.5 microm, was found to correspond to diffraction limit of the imaging
      objective. Selective sensitivity to lipid-rich myelin sheaths in the nerve tissue
      has been demonstrated and confirmed by comparison with histological samples
      stained with myelin-specific dye. Single-shot imaging capability of the system
      has been demonstrated with a speckling-free illumination on a monolayer of 3
      microm polystyrene beads.

PMID- 19399113
TI  - Improved first Rayleigh-Sommerfeld method applied to metallic cylindrical
      focusing micro mirrors.
AB  - An improved first Rayleigh-Sommerfeld method (IRSM1) is intensively applied to
      analyzing the focal properties of metallic cylindrical focusing micro mirrors. A
      variety of metallic cylindrical focusing mirrors with different f-numbers,
      different polarization of incidence, or different types of profiles are
      investigated. The focal properties include the focal spot size, the diffraction
      efficiency, the real focal length, the total reflected power, and the normalized
      sidelobe power. Numerical results calculated by the IRSM1, the original first
      Rayleigh-Sommerfeld method (ORSM1), and the rigorous boundary element method
      (BEM) are presented for quantitative comparison. It is found that the IRSM1 is
      much more accurate than the ORSM1 in performance analysis of metallic cylindrical
      focusing mirrors, especially for cylindrical refractive focusing mirrors with
      small f-numbers. Moreover, the IRSM1 saves great amounts of computational time
      and computer memory in calculations, in comparison with the vectorial BEM.

PMID- 19399114
TI  - Tunable and polarization-selective THz range transmission properties of metallic
      rectangular array with a varying hole channel shape.
AB  - This paper proposes a metallic hole array of a rectangular converging-diverging
      channel (RCDC) shape with extraordinary transmission. We use a three-dimensional
      (3D) finite element method to analyze the transmission characteristics of two
      dimensional metallic hole arrays (2D-MHA) with RCDC. For a straight channel MHA,
      when the aperture size is reduced, the transmission peaks have a blue-shift. The
      same result is observed for a smaller gap throat for the RCDC structure. For the
      rectangular holes with a high length-width ratio, a similar blue-shift in the
      transmission peaks as well as a narrower full width at half maximum (FWHM) are
      observed. The asymmetry from the rectangular shape gives this structure high
      selectivity for light with different polarizations. Furthermore, the RCDC shape
      gives extra degrees of geometrical variables to 2D-MHA for tuning the location of
      the transmission peak and the FWHM. The tunable transmission property of this
      structure shows promise for applications in tunable filters, photonic circuits,
      and biosensors.

PMID- 19399115
TI  - Nonlinear optical properties of phosphorous-doped Si nanocrystals embedded in
      phosphosilicate glass thin films.
AB  - Nonlinear optical properties of phosphorus (P)-doped silicon (Si) nanocrystals
      are studied by z-scan technique in femtosecond regime at around 1.6 eV. The
      nonlinear refractive index (n(2)) and nonlinear absorption coefficient (beta) of
      Si-ncs are significantly enhanced by P-doping. The enhancement of n(2) is
      accompanied by the increase of the linear absorption in the same energy region,
      suggesting that impurity-related energy states are responsible for the
      enhancement of the nonlinear optical response.

PMID- 19399116
TI  - Liquid crystal based electrically switchable Bragg structure for THz waves.
AB  - We demonstrate the first electronically switchable Bragg structure for THz
      frequencies. The structure works as stop-band filter and as mirror. It exhibits
      the 60 GHz broad stop-band around 300 GHz which can be removed by reorienting
      liquid crystal molecules in an external electric field. Our first proof-of
      principle experiments agree very well with transfer matrix calculations.

PMID- 19399117
TI  - Design, optimization and fabrication of an optical mode filter for integrated
      optics.
AB  - We present the design, optimization, fabrication and characterization of an
      optical mode filter, which attenuates the snaking behavior of light caused by a
      lateral misalignment of the input optical fiber relative to an optical circuit.
      The mode filter is realized as a bottleneck section inserted in an optical
      waveguide in front of a branching element. It is designed with Bezier curves. Its
      effect, which depends on the optical state of polarization, is experimentally
      demonstrated by investigating the equilibrium of an optical splitter, which is
      greatly improved however only in TM mode. The measured optical losses induced by
      the filter are 0.28 dB.

PMID- 19399118
TI  - Experimental signature of optical wave thermalization through supercontinuum
      generation in photonic crystal fiber.
AB  - We report an experimental, numerical and theoretical study of the incoherent
      regime of supercontinuum generation in a two zero-dispersion wavelengths fiber.
      By using a simple experimental setup, we show that the phenomenon of spectral
      broadening inherent to supercontinuum generation can be described as a
      thermalization process, which is characterized by an irreversible evolution of
      the optical field towards a thermal equilibrium state. In particular, the
      thermodynamic equilibrium spectrum predicted by the kinetic wave theory is
      characterized by a double peak structure, which has been found in quantitative
      agreement with the numerical simulations without adjustable parameters. We also
      confirm that stimulated Raman scattering leads to the generation of an incoherent
      structure in the normal dispersion regime which is reminiscent of a spectral
      incoherent soliton.

PMID- 19399119
TI  - The effectiveness of detector combinations.
AB  - In this paper, the performance improvement benefiting from the combination of
      local feature detectors for image matching and registration is evaluated.
      Possible combinations of five types of representative interest point detectors
      and region detectors are integrated into the testing framework. The performance
      is compared using the number of correspondences and the repeatability rate, as
      well as an original evaluation criterion named the Reconstruction Similarity
      (RS), which reflects not only the number of matches, but also the degree of
      matching error. It is observed that the combination of DoG extremum and MSCR
      outperforms any single detectors and other detector combinations in most cases.
      Furthermore, MDSS, a hybrid algorithm for accurate image matching, is proposed.
      Compared with standard SIFT and GLOH, its average RS rate exceeds more than
      3.56%, and takes up even less computational time.

PMID- 19399120
TI  - An integral equation based numerical solution for nanoparticles illuminated with
      collimated and focused light.
AB  - To address the large number of parameters involved in nano-optical problems, a
      more efficient computational method is necessary. An integral equation based
      numerical solution is developed when the particles are illuminated with
      collimated and focused incident beams. The solution procedure uses the method of
      weighted residuals, in which the integral equation is reduced to a matrix
      equation and then solved for the unknown electric field distribution. In the
      solution procedure, the effects of the surrounding medium and boundaries are
      taken into account using a Green's function formulation. Therefore, there is no
      additional error due to artificial boundary conditions unlike differential
      equation based techniques, such as finite difference time domain and finite
      element method. In this formulation, only the scattering nano-particle is
      discretized. Such an approach results in a lesser number of unknowns in the
      resulting matrix equation. The results are compared to the analytical Mie series
      solution for spherical particles, as well as to the finite element method for
      rectangular metallic particles. The Richards-Wolf vector field equations are
      combined with the integral equation based formulation to model the interaction of
      nanoparticles with linearly and radially polarized incident focused beams.

PMID- 19399121
TI  - Circularly polarized light in the single-cycle limit: The nature of highly
      polychromatic radiation of defined polarization.
AB  - We have developed a general analytic description of polarized light pulses and
      explored the properties of circularly polarized single-cycle pulses. The temporal
      evolution of the electric-field vector of such spectrally broad pulses, which may
      be described in terms of a Hilbert transform relationship, differs significantly
      from the well-known behavior of quasi-monochromatic radiation. Single-cycle
      circularly polarized pulses are produced and characterized experimentally in the
      terahertz spectral region.

PMID- 19399122
TI  - Doppler-free polarization spectroscopy with a quantum cascade laser at 4.3
      microm.
AB  - We report on what we believe to be the first Doppler-free polarization
      spectroscopy with a quantum cascade laser. A hot-band CO(2) transition around 4.3
      microm wavelength has been used to test the potential of the technique for high
      resolution spectroscopy and wide-bandwidth quantum cascade laser frequency
      stabilization.

PMID- 19399123
TI  - Enhanced forward efficiency of Y3Al5O12:Ce3+ phosphor from white light-emitting
      diodes using blue-pass yellow-reflection filter.
AB  - This paper reports a simple approach for the design of blue-excitation-light
      passing and phosphor-yellow-emission-light reflecting dielectric multilayers to
      recycle the backward emission of Y(3)Al(5)O(12):Ce(3+) (YAG:Ce) yellow phosphors
      on top of a blue InGaN light-emitting diode (LED) cup. The insertion of modified
      quarter-wave films of alternate high- and low-refractive index dielectric films
      (TiO(2)/SiO(2)) into the interface between a YAG:Ce phosphor layer and glass
      substrate resulted in 1.64 and 1.95 fold increase in efficiency and luminous
      efficacy of the forward white emission compared with that of a conventional
      phosphor on top of a blue LED cup with a lower correlated color temperature (<
      4000 K).

PMID- 19399124
TI  - Enhanced quantum efficiency of the visible light photon counter in the
      ultraviolet wavelengths.
AB  - The visible light photon counter (VLPC) is a very high quantum efficiency (QE,
      88% at 694 nm) single photon detector in the visible wavelengths. The QE in the
      ultraviolet (UV) wavelenghths is poor in these devices due to absorption in the
      degenerate front contact. We introduce the ultraviolet photon counter (UVPC),
      where the QE in the near UV wavelength range (300-400 nm) is dramatically
      enhanced. The degenerate Si front contact of the VLPC is replaced with a Ti
      Schottky contact, which reduces the absorption of incident photons within the
      contact layer. We demonstrate a system QE of 5.3% at 300 nm and 11% at 370 nm for
      a UVPC with a Ti Schottky contact and a single layer MgF(2) antireflection
      coating.

PMID- 19399125
TI  - Programmable ultrashort-pulsed flying images.
AB  - We report the generation of programmable two-dimensional arrangements of
      ultrashort-pulsed fringe-less Bessel-like beams of extended depth of focus
      (referred to as needle beams) without truncating apertures. A sub-20-fs
      Ti:sapphire laser and a liquid-crystal-on-silicon spatial light modulator (LCoS
      SLM) of high-fidelity temporal transfer in phase-only operation mode were used in
      the experiments. Axicon profiles with ultrasmall conical angles were approximated
      by adapted gray scale distributions. It was demonstrated that digitized image
      information encoded in amplitudephase maps of the needle beams is propagated over
      considerably large distances at minimal cross talk without the need for
      additional relay optics. This experiment represents a physical realization of
      Saari's proposal of spatio-temporally nondiffracting "flying images" on a few
      femtosecond time scale.

PMID- 19399126
TI  - Broadband enhancement of light emission in silicon slot waveguides.
AB  - We investigate the light emission properties of electrical dipole emitters inside
      2-dimensional (2D) and 3-dimensional (3D) silicon slot waveguides and evaluate
      the spontaneous emission enhancement (F(p)) and waveguide coupling ratio (beta).
      Under realistic conditions, we find that greater than 10-fold enhancement in F(p)
      can be achieved, together with a beta as large as 0.95. In contrast to the case
      of high Q optical resonators, such performance enhancements are obtained over a
      broad wavelength region, which can cover the entire emission spectrum of popular
      optical dopants such as Er. The enhanced luminescence efficiency and the strong
      coupling into a limited set of well-defined waveguide modes enables a new class
      of power-efficient, CMOS-compatible, waveguide-based light sources.

PMID- 19399127
TI  - Using chaos for remote sensing of laser radiation.
AB  - An idea is proposed for detecting a weak laser signal from a remote source in the
      presence of strong background noise. The scheme exploits dynamical nonlinearities
      arising from heterodyning signal and reference fields inside an active reference
      laser cavity. This paper shows that for certain reference laser configurations,
      the resulting bifurcations in the reference laser may be used as warning of
      irradiation by a laser source.

PMID- 19399128
TI  - Global optimization of silicon photovoltaic cell front coatings.
AB  - The front-coating (FC) of a solar cell controls its efficiency, determining
      admission of light into the absorbing material and potentially trapping light to
      enhance thin absorbers. Single-layer FC designs are well known, especially for
      thick absorbers where their only purpose is to reduce reflections. Multilayer FCs
      could improve performance, but require global optimization to design. For narrow
      bandwidths, one can always achieve nearly 100% absorption. For the entire solar
      bandwidth, however, a second FC layer improves performance by 6.1% for 256 microm
      wafer-based cells, or by 3.6% for 2 microm thin-film cells, while additional
      layers yield rapidly diminishing returns.

PMID- 19399129
TI  - Compressing surface plasmons for nano-scale optical focusing.
AB  - A major challenge in optics is how to deliver and concentrate light from the
      micron-scale into the nano-scale. Light can not be guided, by conventional
      mechanisms, with optical beam sizes significantly smaller than its wavelength due
      to the diffraction limit. On the other hand, focusing of light into very small
      volumes beyond the diffraction limit can be achieved by exploiting the wavelength
      scalability of surface plasmon polaritons. By slowing down an optical wave and
      shrinking its wavelength during its propagation, optical energy can be compressed
      and concentrated down to nanometer scale, namely, nanofocusing. Here, we
      experimentally demonstrate and quantitatively measure the nanofocusing of surface
      plasmon polaritons in tapered metallic V-grooves down to the deep subwavelength
      scale - approximately lambda/40 at wavelength of 1.5 micron - with almost 50%
      power efficiency.

PMID- 19399130
TI  - Frequency stabilization of a single mode terahertz quantum cascade laser to the
      kilohertz level.
AB  - A simple analog locking circuit was shown to stabilize the beat signal between a
      2.408 THz quantum cascade laser and a CH(2)DOH THz CO(2) optically pumped
      molecular laser to 3-4 kHz (FWHM). This is approximately a tenth of the observed
      long-term (t approximately sec) linewidth of the optically pumped laser showing
      that the feedback loop corrects for much of the mechanical and acoustic-induced
      frequency jitter of the gas laser. The achieved stability should be sufficient to
      enable the use of THz quantum cascade lasers as transmitters in short-range
      coherent transceivers.

PMID- 19399131
TI  - High-resolution time-of-flight terahertz tomography using a femtosecond fiber
      laser.
AB  - High-resolution tomographic imaging is demonstrated using a reflection-type
      terahertz time-domain spectroscopy. To realize a practical system for general
      use, a robust all-fiber laser was used as the pump light source. Broadband
      terahertz waves were generated with the combination of optical pulses compressed
      to 17 fs using optical fibers and a DAST crystal. Using deconvolution signal
      processing, the wideband spectrum of the generated terahertz waves provided high
      axial resolution leading to successful imaging of a multilayered structure
      containing a 2-microm-thin GaAs layer. To our knowledge, this is the first
      demonstration of terahertz tomographic imaging of such a thin layer.

PMID- 19399133
TI  - A subwavelength coupler-type MIM optical filter.
AB  - A novel subwavelength surface plasmon polaritons optical filter based on an
      incompletely directional coupler is proposed and numerically simulated by using
      the finite difference time domain method with perfectly matched layer absorbing
      boundary condition. An analytical solution for the resonant condition of the
      structure is derived by means of the cavity theory. Both analytical and
      simulative results reveal that the resonant wavelengths are proportional to the
      length of the slit segment, inversely proportional to the antinode number of a
      standing wave in the segment, and are related to the slit width and the gap
      between the two slits. The analytical solution being consistent with the
      numerical simulation verifies the feasibility of the concept of the new filter
      structure.

PMID- 19399132
TI  - Fiber Bragg gratings inscribed using 800nm femtosecond laser and a phase mask in
      single- and multi-core mid-IR glass fibers.
AB  - For the first time, Fiber Bragg grating (FBG) structures have been inscribed in
      single-core passive germanate and three-core passive and active tellurite glass
      fibers using 800 nm femtosecond (fs) laser and phase mask technique. With fs peak
      power intensity in the order of 10(11)W/cm(2), the FBG spectra with 2nd and 3rd
      order resonances at 1540 and 1033 nm in the germanate glass fiber and 2nd order
      resonances at approximately 1694 and approximately 1677 nm with strengths up to
      14 dB in all three cores in the tellurite fiber were observed. Thermal
      responsivities of the FBGs made in these mid-IR glass fibers were characterized,
      showing average temperature responsivity approximately 20 pm/ degrees C. Strain
      responsivities of the FBGs in germanate glass fiber were measured to be 1.219
      pm/microepsilon.

PMID- 19399134
TI  - Hybrid electronic/optical synchronized chaos communication system.
AB  - A hybrid electronic/optical system for synchronizing a chaotic receiver to a
      chaotic transmitter has been demonstrated. The chaotic signal is generated
      electronically and injected, in addition to a constant bias current, to a
      semiconductor laser to produce an optical carrier for transmission. The optical
      chaotic carrier is photodetected to regenerate an electronic signal for
      synchronization in a matched electronic receiver The system has been successfully
      used for the transmission and recovery of a chaos masked message that is added to
      the chaotic optical carrier. Past demonstrations of synchronized chaos based,
      secure communication systems have used either an electronic chaotic carrier or an
      optical chaotic carrier (such as the chaotic output of various nonlinear laser
      systems). This is the first electronic/optical hybrid system to be demonstrated.
      We call this generation of a chaotic optical carrier by electronic injection.

PMID- 19399135
TI  - Exceptionally efficient organic light emitting devices using high refractive
      index substrates.
AB  - Organic light emitting devices (OLEDs) are now used in commercial cell phones and
      flat screen displays, but may become even more successful in lighting
      applications, in which large area, high efficiency, long lifetime and low cost
      are essential. Due to the relatively high refractive index of the organic layers,
      conventional planar bottom emitting OLEDs have a low outcoupling efficiency.
      Various approaches for enhancing the optical outcoupling efficiency of bottom
      emitting OLEDs have been introduced in the literature. In this paper we
      demonstrate a green bottom emitting OLED with a record external quantum
      efficiency (42%) and luminous efficacy (183 lm/W). This OLED is based on a high
      index substrate and a thick electron transport layer (ETL) which uses electrical
      doping. The efficient light outcoupling is modeled by optical simulations.

PMID- 19399137
TI  - Pulse broadening cancellation in cascaded slow-light delays.
AB  - This article describes a new approach to cancel the pulse broadening in a
      cascaded slow-light system. With the help of a simple experimental setup a method
      with significant potential to achieve a high pulse delay at almost zero pulse
      broadening is shown. Since the pulse reshaping is done inside a single delaying
      segment, this method can be used in connection with any other Brillouin based
      slow-light system.

PMID- 19399136
TI  - A three-dimensional multispectral fluorescence optical tomography imaging system
      for small animals based on a conical mirror design.
AB  - We have developed a three dimensional (3D) multispectral fluorescence optical
      tomography small animal imaging system with an innovative geometry using a
      truncated conical mirror, allowing simultaneous viewing of the entire surface of
      the animal by an EMCCD camera. A conical mirror collects photons approximately
      three times more efficiently than a flat mirror. An x-y mirror scanning system
      makes it possible to scan a collimated excitation laser beam to any location on
      the mouse surface. A pattern of structured light incident on the small animal
      surface is used to extract the surface geometry for reconstruction. A finite
      element based algorithm is applied to model photon propagation in the turbid
      media and a preconditioned conjugate gradient (PCG) method is used to solve the
      large linear system matrix. The reconstruction algorithm and the system
      feasibility are evaluated by phantom experiments. These experiments show that
      multispectral measurements improve the spatial resolution of reconstructed
      images. Finally, an in vivo imaging study of a xenograft tumor in a mouse shows
      good correlation of the reconstructed image with the location of the fluorescence
      probe as determined by subsequent optical imaging of cryosections of the mouse.

PMID- 19399138
TI  - Automated correlation dimension analysis of optically injected solid state
      lasers.
AB  - Nonlinear lasers are excellent systems from which to obtain high signal-to-noise
      experimental data of nonlinear dynamical variables to be used to develop and
      demonstrate robust nonlinear dynamics analysis techniques. Here we investigate
      the dynamical complexity of such a system: an optically injected Nd:YVO(4) solid
      state laser. We show that a map of the correlation dimension as a function of the
      injection strength and frequency detuning, extracted from the laser output power
      time-series data, is an excellent mirror of the dynamics map generated from a
      theoretical model of the system. An automated computational protocol has been
      designed and implemented to achieve this. The correlation dimension map is also
      contrasted with prior research that mapped the peak intensity of the output power
      as an experimentally accessible measurand reflecting the dynamical state of the
      system [Valling et al., Phys. Rev. A 72, 033810 (2005)].

PMID- 19399139
TI  - RF phase shifter using a distributed feedback laser in microwave transport
      systems.
AB  - This work experimentally demonstrates the efficacy of a radio-frequency phase
      shifter using a distributed feedback laser in a microwave transport system. Phase
      shifts of about 101 degrees are obtained at 8.75 GHz. The proposed phase shifter
      can amplify microwave signals and thereby improve transmission performance.
      Additionally, a similar single sideband modulation can be generated by the phase
      shifter. Experimental results indicate that the proposed phase shifter can be
      used in future long-distance microwave transport systems and all optical
      inverters.

PMID- 19399140
TI  - Detailed theoretical investigation of bending properties in solid-core photonic
      bandgap fibers.
AB  - In this paper, detailed properties of bent solid-core photonic bandgap fibers (SC
      PBGFs) are investigated. We propose an approximate equivalent straight waveguide
      (ESW) formulation for photonic bandgap (PBG) edges, which is convenient to see
      qualitatively which radiation (centripetal or centrifugal radiation) mainly
      occurs and the impact of bend losses for an operating wavelength. In particular,
      we show that cladding modes induced by bending cause several complete or
      incomplete leaky mode couplings with the core mode and the resultant loss peaks.
      Moreover, we show that the field distributions of the cladding modes are
      characterized by three distinct types for blue-edge, mid-gap, and red-edge
      wavelengths in the PBG, which is explained by considering the cladding Bloch
      states or resonant conditions without bending. Next, we investigate the
      structural dependence of the bend losses. In particular, we demonstrate the bend
      loss dependence on the number of the cladding rings. Finally, by investigating
      the impacts of the order of PBG and the core structure on the bend losses, we
      discuss a tight-bending structure.

PMID- 19399141
TI  - Insights into tunnelling rays: outperforming guided rays in fiber-optic sensing
      device.
AB  - We report that, for an evanescent-wave (EW) based fiber-optic sensor, the less
      skewed tunnelling rays and a small number of very steep guided rays experience
      total internal reflection (TIR) at one end-face of the air-clad fiber segment. As
      a result, they demonstrate nine times greater efficiency in collecting EW-power
      than rays that do not exhibit end-face- TIR. This tunneling ray group originates
      from a launching ring that is seven times wider than that of end-face-TIR capable
      guided rays, enabling it to dominate the overall detected EW-power level.
      Strongly supporting this conclusion is the counter-intuitive experimental
      observation that the detected power at one end of the fiber abruptly drops 91%
      when the back reflection at the opposite end is eliminated, while an isotropic
      light source is placed at the core-cladding interface between these two ends. The
      mechanism of non-propagating ray excitation accounts for this high efficiency. We
      also indicate that many highly skewed tunnelling rays are naturally isolated from
      the external world because, outside the fiber core, they are accessible only via
      their EW fields even at the fiber end-faces. The findings reported here have
      significant implications for the design of future high-performance EW-based fiber
      sensing devices for the analysis of surface-event.

PMID- 19399142
TI  - An efficient broadband metamaterial wave retarder.
AB  - Metamaterials with anisotropic electromagnetic properties have the capability to
      manipulate the polarization states of electromagnetic waves. We describe a method
      to design a broadband, low-loss wave retarder with graded constitutive parameter
      distributions based on non-resonant metamaterial elements. A structured
      metamaterial half-wave retarder that converts one linear polarization to its
      cross polarization is designed and its performance is characterized
      experimentally.

PMID- 19399143
TI  - Strong-field two-photon absorption in atomic cesium: an analytical control
      approach.
AB  - We have considered an analytical control of two-photon absorption process of
      atoms in the strong-field interaction regime. The experiment was performed on
      gaseous cesium atoms strongly interacting with a shaped laser-pulse from a
      femtosecond laser amplifier and a programmable pulse-shaper. When this shaped
      laser-pulse transfers the atomic population from the 6s ground state to the 8s
      excited state, we have found that both positively- and negatively-chirped laser
      pulses, compared with a Gaussian pulse, enhance this excitation in the strong
      field regime of laser-atom interaction. This unusual phenomena is explained
      because the temporal shape of the laser intensity compensates the effect of
      dynamic Stark shift for the two-photon resonant condition to be optimally
      maintained. We provide analytic calculations using the strong-field phase
      matching, which show good agreement with the experiment.

PMID- 19399144
TI  - Efficient sub-wavelength light confinement using surface plasmon polaritons in
      tapered fibers.
AB  - Light confinement to sub-wavelength spot sizes is proposed and realized in
      tapered optical fibers. To achieve high transmission efficiencies, light
      propagating along the taper is combined with the excitation of surface plasmon
      polaritons (SPP) at its tip.

PMID- 19399145
TI  - A widely tunable wavelength converter based on nonlinear polarization rotation in
      a carbon-nanotube-deposited D-shaped fiber.
AB  - We demonstrate widely tunable wavelength conversion based on cross-phase
      modulation induced nonlinear polarization rotation in a carbon nanotubes (CNTs)
      deposited D-shaped fiber. A 5-centimeter-long CNT-deposited D-shaped fiber is
      used as the nonlinear medium for wavelength conversion of a 10 Gb/s non-return-to
      zero signal. Wavelength tunable converted signal over 40 nm is obtained with
      around 2.5-dB power penalty in the bit-error-rate measurements.

PMID- 19399146
TI  - Absorption and quasiguided mode analysis of organic solar cells with photonic
      crystal photoactive layers.
AB  - We analyze optical absorption enhancements and quasiguided mode properties of
      organic solar cells with highly ordered nanostructured photoactive layers
      comprised of the bulk heterojunction blend, poly-3-hexylthiophene/[6,6]-phenyl
      C61-butyric acid methyl ester (P3HT:PCBM) and a low index of refraction
      conducting material (LICM). This photonic crystal geometry is capable of
      enhancing spectral absorption by approximately 17% in part due to the excitation
      of quasiguided modes near the band edge of P3HT:PCBM. A nanostructure thickness
      between 200 nm and 300 nm is determined to be optimal, while the LICM must have
      an index of refraction approximately 0.3 lower than P3HT:PCBM to produce
      absorption enhancements. Quasiguided modes that differ in lifetime by an order of
      magnitude are also identified and yield absorption that is concentrated in the
      P3HT:PCBM flash layer.

PMID- 19399147
TI  - Metastable Magnesium fluorescence spectroscopy using a frequency-stabilized 517
      nm laser.
AB  - We present a laser operating at 517 nm for our Magnesium laser-cooling and atomic
      clock project. A two-stage Yb-doped fiber amplifier (YDFA) system generates more
      than 1.5 W of 1034 nm light when seeded with a 15 mW diode laser. Using a
      periodically poled lithium niobate (PPLN) waveguide, we obtained more than 40 mW
      of 517 nm output power by single pass frequency doubling. In addition,
      fluorescence spectroscopy of metastable magnesium atoms could be used to
      stabilize the 517 nm laser to an absolute frequency within 1 MHz.

PMID- 19399148
TI  - Noninvasive label-free imaging of microhemodynamics by optical-resolution
      photoacoustic microscopy.
AB  - In vivo microcirculatory imaging facilitates the fundamental understanding of
      many major diseases. However, existing techniques generally require invasive
      procedures or exogenous contrast agents, which perturb the intrinsic physiology
      of the microcirculation. Here, we report on optical-resolution photoacoustic
      microscopy (OR-PAM) for noninvasive label-free microcirculatory imaging at
      cellular levels. For the first time, OR-PAM demonstrates quantification of
      hemoglobin concentration and oxygenation in single microvessels down to
      capillaries. Using this technique, we imaged several important yet elusive
      microhemodynamic activities-including vasomotion and vasodilation-in small
      animals in vivo. OR-PAM enables functional volumetric imaging of the intact
      microcirculation, thereby providing greatly improved accuracy and versatility for
      broad biological and clinical applications.

PMID- 19399149
TI  - Self-organization of arrays of two mutually-injected fiber lasers: theoretical
      investigation.
AB  - The array of two mutually-injected fiber lasers is theoretically studied. It is
      found that the self-organization mechanism of this array is virtually the
      longitudinal-mode competition in the compound laser cavity. Two phase-locked
      states of this array are predicted. The performance of this array is also
      investigated, and the theoretical result agrees well with the experimental
      observation. Based on the theoretical analysis, some advices for building this
      array are also given.

PMID- 19399150
TI  - Continuous-wave optical parametric oscillator tuned by a diffraction grating.
AB  - A new continuous-wave singly resonant optical parametric oscillator is described.
      It is capable of stable, widely tunable single-frequency output in the mid
      infrared region. A magnesium oxide doped periodically poled LiNbO(3) crystal
      provides the parametric amplification. The signal beam is in resonance with a 4
      mirror linear cavity, where a diffraction grating in the Littrow configuration
      replaces one end mirror. The output frequency is tunable by rotating the grating.
      No additional components are needed inside the resonator.

PMID- 19399151
TI  - Fano-resonance-based Mach-Zehnder optical switch employing dual-bus coupled ring
      resonator as two-beam interferometer.
AB  - A kind of Mach-Zehnder optical switch with a dual-bus coupled ring resonator as a
      two-beam interferometer is proposed and investigated. The analysis based on the
      transfer matrix method shows that a sharp asymmetric Fano line shape can be
      generated in the transmission spectra of such a configuration, which can be used
      to significantly reduce the phase change required for switching. Meanwhile, it
      can also be found that complete extinctions can be achieved in both switching
      states if the structural parameters are carefully chosen and the phase bias is
      properly set. Through tuning the phase difference between the arms of the Mach
      Zehnder interferometer, complete extinction can be easily kept within a large
      range of the ring-bus coupling ratios in the OFF state. By properly modulating
      the phase change in the ring waveguide, the shift of the resonant frequency and
      the asymmetry of the transmission spectra can be controlled to finally enable
      optical switching with a high extinction ratio, even complete extinction, in the
      ON state. The switching functionality is verified by the finite-difference time
      domain simulation.

PMID- 19399152
TI  - Crosstalk-free design for the intersection of two dielectric waveguides.
AB  - We propose an efficient method to reduce the crosstalk, reflection and radiation
      at the crossing of two dielectric waveguides in a on-chip optical interconnect
      network. By increasing the vertical thickness of the guides locally in the
      crossing region, we create better mode-matching interfaces that dramatically
      reduce losses. The idea is demonstrated using numerical simulations. More than
      95% crosstalk power reduction and 90% reflection power reduction are observed,
      while the radiation power can be reduced by 40%. The method is compatible with
      the planar integrated circuit technique.

PMID- 19399153
TI  - Abstracts of the Combined Annual Scientific Meeting of the Trauma Association of
      Canada and the Australasian Trauma Society 2008. April 3-5, 2008. Whistler,
      British Columbia, Canada.

PMID- 19399154
TI  - Rapid scale-up of antiretroviral treatment in Ethiopia: successes and system-wide
      effects.

PMID- 19399155
TI  - The Millennium Development Goals fail poor children: the case for equity-adjusted
      measures.

PMID- 19399156
TI  - Influence of rapid malaria diagnostic tests on treatment and health outcome in
      fever patients, Zanzibar: a crossover validation study.
AB  - BACKGROUND: The use of rapid diagnostic tests (RDTs) for Plasmodium falciparum
      malaria is being suggested to improve diagnostic efficiency in peripheral health
      care settings in Africa. Such improved diagnostics are critical to minimize
      overuse and thereby delay development of resistance to artemisinin-based
      combination therapies (ACTs). Our objective was to study the influence of RDT
      aided malaria diagnosis on drug prescriptions, health outcomes, and costs in
      primary health care settings. METHODS AND FINDINGS: We conducted a cross-over
      validation clinical trial in four primary health care units in Zanzibar. Patients
      of all ages with reported fever in the previous 48 hours were eligible and
      allocated alternate weeks to RDT-aided malaria diagnosis or symptom-based
      clinical diagnosis (CD) alone. Follow-up was 14 days. ACT was to be prescribed to
      patients diagnosed with malaria in both groups. Statistical analyses with
      multilevel modelling were performed. A total of 1,887 patients were enrolled
      February through August 2005. RDT was associated with lower prescription rates of
      antimalarial treatment than CD alone, 361/1005 (36%) compared with 752/882 (85%)
      (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.03-0.05, p<0.001).
      Prescriptions of antibiotics were higher after RDT than CD alone, i.e., 372/1005
      (37%) and 235/882 (27%) (OR 1.8, 95%CI 1.5-2.2, p<0.001), respectively.
      Reattendance due to perceived unsuccessful clinical cure was lower after RDT
      25/1005 (2.5%), than CD alone 43/882 (4.9%) (OR 0.5, 95% CI 0.3-0.9, p = 0.005).
      Total average cost per patient was similar: USD 2.47 and 2.37 after RDT and CD
      alone, respectively. CONCLUSIONS: RDTs resulted in improved adequate treatment
      and health outcomes without increased cost per patient. RDTs may represent a tool
      for improved management of patients with fever in peripheral health care
      settings. TRIAL REGISTRATION: (Clinicaltrials.gov) NCT00549003.

PMID- 19399157
TI  - Mortality of HIV-infected patients starting antiretroviral therapy in sub-Saharan
      Africa: comparison with HIV-unrelated mortality.
AB  - BACKGROUND: Mortality in HIV-infected patients who have access to highly active
      antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is
      unclear how mortality compares to the non-HIV-infected population. We compared
      mortality rates observed in HIV-1-infected patients starting ART with non-HIV
      related background mortality in four countries in sub-Saharan Africa. METHODS AND
      FINDINGS: Patients enrolled in antiretroviral treatment programmes in Cote
      d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess
      mortality rates and standardised mortality ratios (SMRs) with 95% confidence
      intervals (CIs). Expected numbers of deaths were obtained using estimates of age
      , sex-, and country-specific, HIV-unrelated, mortality rates from the Global
      Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were
      recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831
      (67%) patients were female, and 10,811 of 12,720 patients (85%) with information
      on clinical stage had advanced disease when starting ART. The excess mortality
      rate was 17.5 (95% CI 14.5-21.1) per 100 person-years SMR in patients who started
      ART with a CD4 cell count of less than 25 cells/microl and World Health
      Organization (WHO) stage III/IV, compared to 1.00 (0.55-1.81) per 100 person
      years in patients who started with 200 cells/microl or above with WHO stage I/II.
      The corresponding SMRs were 47.1 (39.1-56.6) and 3.44 (1.91-6.17). Among patients
      who started ART with 200 cells/microl or above in WHO stage I/II and survived the
      first year of ART, the excess mortality rate was 0.27 (0.08-0.94) per 100 person
      years and the SMR was 1.14 (0.47-2.77). CONCLUSIONS: Mortality of HIV-infected
      patients treated with combination ART in sub-Saharan Africa continues to be
      higher than in the general population, but for some patients excess mortality is
      moderate and reaches that of the general population in the second year of ART.
      Much of the excess mortality might be prevented by timely initiation of ART.

PMID- 19399158
TI  - Global health actors claim to support health system strengthening: is this
      reality or rhetoric?

PMID- 19399159
TI  - A medical journal for the world's health priorities.

PMID- 19399160
TI  - The role of rapid diagnostic tests in managing malaria.

PMID- 19399162
TI  - Echinococcus granulosus infection and options for control of cystic
      echinococcosis in Tibetan communities of Western Sichuan Province, China.
AB  - BACKGROUND: Human cystic echinococcosis (CE) is highly endemic in the Tibetan
      regions of Sichuan where most families keep guard dogs and where there are
      considerable numbers of ownerless/stray dogs. Strong Buddhist beliefs do not
      allow for elimination of stray dogs, and many strays are actually fed and adopted
      by households or monasteries. On account of the high altitude (3900-5000 m),
      pasturage is the major agricultural activity in this area. The harsh mountainous
      climate often leads to many grazing animals dying on the pasture at the end of a
      hard winter. The skin and some meat are taken, and the rest of the animal is left
      for scavenging birds and animals. The poor sanitation and hygiene, the Buddhist
      doctrine of allowing old livestock to die naturally, plus the unrestricted
      disposal of animal viscera post-slaughter may be responsible for the high
      prevalence of human CE in this setting. METHODS AND FINDINGS: As part of a large
      collaborative control program for CE in Ganzi County, situated in the west of
      Sichuan Province, surveillance for Echinococcus infection in domestic dogs using
      a coproantigen method and necropsy of unwanted dogs was carried out prior to (in
      2000) and after (in 2005) dog anthelminthic treatment (5 mg/kg oral praziquantal
      at 6 month intervals) to determine the efficacy of the treatment for control. The
      prevalence of E. granulosus only in dogs by necropsy was 27% and 22%, and
      prevalence of both Echinococcus spp. by necropsy was 63% and 38%; prevalence of
      both Echinococcus spp. by coproantigen analysis was 50% and 17%. Necropsy of
      sheep/goats (age <1 to 12 years) (prevalence of E. granulosus in 1-6-year-old
      animals was 38% and in 10-12-year-old animals was 70%) and yaks (age 4 years)
      (prevalence of E. granulosus was 38%) was undertaken to determine the baseline
      transmission pressure. Protoscoleces were only found in very old sheep/goats and
      yaks. Necropsy of dogs in the Datangma district indicated that there was no
      apparent significant change in the overall prevalence of E. granulosus in
      unwanted dogs after 5 years of 6-month praziquantel treatment. However, this was
      likely due to the number of dogs available for necropsy being too small to
      reflect the real situation prevailing. There was a highly significant decrease in
      Echinococcus prevalence after the 5-year treatment program shown by coproantigen
      ELISA. This indicated a decreasing but continuing risk for re-infection of
      domestic and stray dogs. Genotyping of E. granulosus samples obtained from
      necropsied sheep/goats and yaks and from locally infected humans at surgery was
      carried out to determine the strain of parasite responsible for human infection.
      DNA genotyping indicated that only the sheep strain (G1) of E. granulosus was
      present in the study area. CONCLUSIONS: Considerable re-infection rates of E.
      granulosus among dogs indicated a high infection pressure from infected livestock
      in this region, most likely from older animals dying on the pasture. A
      combination of livestock vaccination with the Eg95 vaccine, which is effective
      against the sheep strain of E. granulosus, and dog anthelmintic treatment, thus
      targeting two critical points of the parasite life-cycle, would avoid the
      conflicts of religion or local culture and could achieve the goal of hydatid
      control in the long term.

PMID- 19399161
TI  - The preventable causes of death in the United States: comparative risk assessment
      of dietary, lifestyle, and metabolic risk factors.
AB  - BACKGROUND: Knowledge of the number of deaths caused by risk factors is needed
      for health policy and priority setting. Our aim was to estimate the mortality
      effects of the following 12 modifiable dietary, lifestyle, and metabolic risk
      factors in the United States (US) using consistent and comparable methods: high
      blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure;
      overweight-obesity; high dietary trans fatty acids and salt; low dietary
      polyunsaturated fatty acids, omega-3 fatty acids (seafood), and fruits and
      vegetables; physical inactivity; alcohol use; and tobacco smoking. METHODS AND
      FINDINGS: We used data on risk factor exposures in the US population from
      nationally representative health surveys and disease-specific mortality
      statistics from the National Center for Health Statistics. We obtained the
      etiological effects of risk factors on disease-specific mortality, by age, from
      systematic reviews and meta-analyses of epidemiological studies that had adjusted
      (i) for major potential confounders, and (ii) where possible for regression
      dilution bias. We estimated the number of disease-specific deaths attributable to
      all non-optimal levels of each risk factor exposure, by age and sex. In 2005,
      tobacco smoking and high blood pressure were responsible for an estimated 467,000
      (95% confidence interval [CI] 436,000-500,000) and 395,000 (372,000-414,000)
      deaths, accounting for about one in five or six deaths in US adults. Overweight
      obesity (216,000; 188,000-237,000) and physical inactivity (191,000; 164,000
      222,000) were each responsible for nearly 1 in 10 deaths. High dietary salt
      (102,000; 97,000-107,000), low dietary omega-3 fatty acids (84,000; 72,000
      96,000), and high dietary trans fatty acids (82,000; 63,000-97,000) were the
      dietary risks with the largest mortality effects. Although 26,000 (23,000-40,000)
      deaths from ischemic heart disease, ischemic stroke, and diabetes were averted by
      current alcohol use, they were outweighed by 90,000 (88,000-94,000) deaths from
      other cardiovascular diseases, cancers, liver cirrhosis, pancreatitis, alcohol
      use disorders, road traffic and other injuries, and violence. CONCLUSIONS:
      Smoking and high blood pressure, which both have effective interventions, are
      responsible for the largest number of deaths in the US. Other dietary, lifestyle,
      and metabolic risk factors for chronic diseases also cause a substantial number
      of deaths in the US.

PMID- 19399163
TI  - Use of mapping and spatial and space-time modeling approaches in operational
      control of Aedes aegypti and dengue.
AB  - The aims of this review paper are to 1) provide an overview of how mapping and
      spatial and space-time modeling approaches have been used to date to visualize
      and analyze mosquito vector and epidemiologic data for dengue; and 2) discuss the
      potential for these approaches to be included as routine activities in
      operational vector and dengue control programs. Geographical information system
      (GIS) software are becoming more user-friendly and now are complemented by free
      mapping software that provide access to satellite imagery and basic feature
      making tools and have the capacity to generate static maps as well as dynamic
      time-series maps. Our challenge is now to move beyond the research arena by
      transferring mapping and GIS technologies and spatial statistical analysis
      techniques in user-friendly packages to operational vector and dengue control
      programs. This will enable control programs to, for example, generate risk maps
      for exposure to dengue virus, develop Priority Area Classifications for vector
      control, and explore socioeconomic associations with dengue risk.

PMID- 19399164
TI  - Development and evaluation of two simple, rapid immunochromatographic tests for
      the detection of Yersinia pestis antibodies in humans and reservoirs.
AB  - BACKGROUND: Tools for plague diagnosis and surveillance are not always available
      and affordable in most of the countries affected by the disease. Yersinia pestis
      isolation for confirmation is time-consuming and difficult to perform under field
      conditions. Serologic tests like ELISA require specific equipments not always
      available in developing countries. In addition to the existing rapid test for
      antigen detection, a rapid serodiagnostic assay may be useful for plague control.
      METHODS/PRINCIPAL FINDINGS: We developed two rapid immunochromatography-based
      tests for the detection of antibodies directed against F1 antigen of Y. pestis.
      The first test, SIgT, which detects total Ig (IgT) anti-F1 in several species (S)
      (human and reservoirs), was developed in order to have for the field use an
      alternative method to ELISA. The performance of the SIgT test was evaluated with
      samples from humans and animals for which ELISA was used to determine the
      presumptive diagnosis of plague. SIgT test detected anti-F1 Ig antibodies in
      humans with a sensitivity of 84.6% (95% CI: 0.76-0.94) and a specificity of 98%
      (95% CI: 0.96-1). In evaluation of samples from rodents and other small mammals,
      the SlgT test had a sensitivity of 87.8% (95% CI: 0.80-0.94) and a specificity of
      90.3% (95% CI: 0.86-0.93). Improved performance was obtained with samples from
      dogs, a sentinel animal, with a sensitivity of 93% (95% CI: 0.82-1) and a
      specificity of 98% (95% CI: 0.95-1.01). The second test, HIgM, which detects
      human (H) IgM anti-F1, was developed in order to have another method for plague
      diagnosis. Its sensitivity was 83% (95% CI: 0.75-0.90) and its specificity about
      100%. CONCLUSION/SIGNIFICANCE: The SIgT test is of importance for surveillance
      because it can detect Ig antibodies in a range of reservoir species. The HIgM
      test could facilitate the diagnosis of plague during outbreaks, particularly when
      only a single serum sample is available.

PMID- 19399165
TI  - One world health: neglected tropical diseases in a flat world.

PMID- 19399167
TI  - Conducting research in disease outbreaks.

PMID- 19399166
TI  - Dengue virus serotype 2 from a sylvatic lineage isolated from a patient with
      dengue hemorrhagic fever.
AB  - Dengue viruses circulate in both human and sylvatic cycles. Although dengue
      viruses (DENV) infecting humans can cause major epidemics and severe disease,
      relatively little is known about the epidemiology and etiology of sylvatic dengue
      viruses. A 20-year-old male developed dengue hemorrhagic fever (DHF) with
      thrombocytopenia (12,000/ul) and a raised hematocrit (29.5% above baseline) in
      January 2008 in Malaysia. Dengue virus serotype 2 was isolated from his blood on
      day 4 of fever. A phylogenetic analysis of the complete genome sequence revealed
      that this virus was a member of a sylvatic lineage of DENV-2 and most closely
      related to a virus isolated from a sentinel monkey in Malaysia in 1970. This is
      the first identification of a sylvatic DENV circulating in Asia since 1975.

PMID- 19399168
TI  - Effects of a five-year citywide intervention program to control Aedes aegypti and
      prevent dengue outbreaks in northern Argentina.
AB  - BACKGROUND: Dengue has propagated widely through the Americas. Most countries
      have not been able to maintain permanent larval mosquito control programs, and
      the long-term effects of control actions have rarely been documented.
      METHODOLOGY: The study design was based on a before-and-after citywide assessment
      of Aedes aegypti larval indices and the reported incidence of dengue in Clorinda,
      northeastern Argentina, over 2003-2007. Interventions were mainly based on focal
      treatment with larvicides of every mosquito developmental site every four months
      (14 cycles), combined with limited source reduction efforts and ultra-low-volume
      insecticide spraying during emergency operations. The program conducted 120,000
      house searches for mosquito developmental sites and 37,000 larvicide
      applications. PRINCIPAL FINDINGS: Random-effects regression models showed that
      Breteau indices declined significantly in nearly all focal cycles compared to pre
      intervention indices clustered by neighborhood, after allowing for lagged effects
      of temperature and rainfall, baseline Breteau index, and surveillance coverage.
      Significant heterogeneity between neighborhoods was revealed. Larval indices
      seldom fell to 0 shortly after interventions at the same blocks. Large water
      storage containers were the most abundant and likely to be infested. The reported
      incidence of dengue cases declined from 10.4 per 10,000 in 2000 (by DEN-1) to 0
      from 2001 to 2006, and then rose to 4.5 cases per 10,000 in 2007 (by DEN-3). In
      neighboring Paraguay, the reported incidence of dengue in 2007 was 30.6 times
      higher than that in Clorinda. CONCLUSIONS: Control interventions exerted
      significant impacts on larval indices but failed to keep them below target levels
      during every summer, achieved sustained community acceptance, most likely
      prevented new dengue outbreaks over 2003-2006, and limited to a large degree the
      2007 outbreak. For further improvement, a shift is needed towards a multifaceted
      program with intensified coverage and source reduction efforts, lids or
      insecticide-treated covers to water-storage containers, and a broad social
      participation aiming at long-term sustainability.

PMID- 19399169
TI  - Introduction of dengue virus 4 (DENV-4) genotype I into Brazil from Asia?

PMID- 19399170
TI  - Identifying hubs in protein interaction networks.
AB  - BACKGROUND: In spite of the scale-free degree distribution that characterizes
      most protein interaction networks (PINs), it is common to define an ad hoc degree
      scale that defines "hub" proteins having special topological and functional
      significance. This raises the concern that some conclusions on the functional
      significance of proteins based on network properties may not be robust.
      METHODOLOGY: In this paper we present three objective methods to define hub
      proteins in PINs: one is a purely topological method and two others are based on
      gene expression and function. By applying these methods to four distinct PINs, we
      examine the extent of agreement among these methods and implications of these
      results on network construction. CONCLUSIONS: We find that the methods agree well
      for networks that contain a balance between error-free and unbiased interactions,
      indicating that the hub concept is meaningful for such networks.

PMID- 19399171
TI  - Extraction and inhibition of enzymatic activity of botulinum neurotoxins/A1, /A2,
      and /A3 by a panel of monoclonal anti-BoNT/A antibodies.
AB  - Botulinum neurotoxins (BoNTs) are extremely potent toxins that are capable of
      causing death or respiratory failure leading to long-term intensive care.
      Treatment includes serotype-specific antitoxins, which must be administered early
      in the course of the intoxication. Rapidly determining human exposure to BoNT is
      an important public health goal. In previous work, our laboratory focused on
      developing Endopep-MS, a mass spectrometry-based endopeptidase method for
      detecting and differentiating BoNT/A-G serotypes in buffer and BoNT/A, /B, /E,
      and /F in clinical samples. We have previously reported the effectiveness of
      antibody-capture to purify and concentrate BoNTs from complex matrices, such as
      clinical samples. Because some antibodies inhibit or neutralize the activity of
      BoNT, the choice of antibody with which to extract the toxin is critical. In this
      work, we evaluated a panel of 16 anti-BoNT/A monoclonal antibodies (mAbs) for
      their ability to inhibit the in vitro activity of BoNT/A1, /A2, and /A3 complex
      as well as the recombinant LC of A1. We also evaluated the same antibody panel
      for the ability to extract BoNT/A1, /A2, and /A3. Among the mAbs, there were
      significant differences in extraction efficiency, ability to extract BoNT/A
      subtypes, and inhibitory effect on BoNT catalytic activity. The mAbs binding the
      C-terminal portion of the BoNT/A heavy chain had optimal properties for use in
      the Endopep-MS assay.

PMID- 19399172
TI  - Indirect recruitment of a CD40 signaling pathway in dendritic cells by B7-DC
      cross-linking antibody modulates T cell functions.
AB  - The human IgM B7-DC XAb protects mice from tumors in both therapeutic and
      prophylactic settings. Its mechanism of action is mediated by its binding to B7
      DC/PD-L2 molecules on the surface of dendritic cells (DCs) to induce a
      multimolecular cap and subsequent activation of signaling cascades that determine
      a unique combination of DC phenotypes. One such phenotype, the B7-DC XAb-induced
      antigen accumulation in mTLR-matured DCs, has been linked to signaling through
      TREM-2, but the signals required for other DC phenotypes critical for the
      therapeutic effects in animal models remain unclear. Here, FRET and co
      immunoprecipitation studies show that CD40 is recruited to the multi-molecular
      complex by B7-DC XAb. Signals emanating from CD40 are important, as CD40(-/-) DCs
      treated with B7-DC XAb (DC(XAb)) activated DAP12, but failed to activate
      NFkappaB, and were not protected from cell death upon cytokine withdrawal or
      treatment with Vitamin D(3). CD40(-/-) DC(XAb) also failed to secrete IL-6 and
      were unable to support the conversion of T regulatory cells into IL-17+ effector
      T cells in vitro. Importantly, the expression of CD40 was required for the
      overall ability of B7-DC XAb to induce anti-tumor CTL, to provide protection from
      a number of tumor types, and for DC(XAb) to be effective anti-tumor vaccines in
      vivo. These results indicate that B7-DC XAb modulation of DC phenotypes is
      through its ability to indirectly recruit common signaling molecules and elements
      of their endogenous signaling pathways through targeted binding to a cell
      specific surface determinant.

PMID- 19399173
TI  - Reliable activation of immature neurons in the adult hippocampus.
AB  - Neurons born in the adult dentate gyrus develop, mature, and connect over a long
      interval that can last from six to eight weeks. It has been proposed that, during
      this period, developing neurons play a relevant role in hippocampal signal
      processing owing to their distinctive electrical properties. However, it has
      remained unknown whether immature neurons can be recruited into a network before
      synaptic and functional maturity have been achieved. To address this question, we
      used retroviral expression of green fluorescent protein to identify developing
      granule cells of the adult mouse hippocampus and investigate the balance of
      afferent excitation, intrinsic excitability, and firing behavior by patch clamp
      recordings in acute slices. We found that glutamatergic inputs onto young neurons
      are significantly weaker than those of mature cells, yet stimulation of cortical
      excitatory axons elicits a similar spiking probability in neurons at either
      developmental stage. Young neurons are highly efficient in transducing ionic
      currents into membrane depolarization due to their high input resistance, which
      decreases substantially in mature neurons as the inward rectifier potassium (Kir)
      conductance increases. Pharmacological blockade of Kir channels in mature neurons
      mimics the high excitability characteristic of young neurons. Conversely, Kir
      overexpression induces mature-like firing properties in young neurons. Therefore,
      the differences in excitatory drive of young and mature neurons are compensated
      by changes in membrane excitability that render an equalized firing activity.
      These observations demonstrate that the adult hippocampus continuously generates
      a population of highly excitable young neurons capable of information processing.

PMID- 19399174
TI  - Fault tolerance in protein interaction networks: stable bipartite subgraphs and
      redundant pathways.
AB  - As increasing amounts of high-throughput data for the yeast interactome become
      available, more system-wide properties are uncovered. One interesting question
      concerns the fault tolerance of protein interaction networks: whether there exist
      alternative pathways that can perform some required function if a gene essential
      to the main mechanism is defective, absent or suppressed. A signature pattern for
      redundant pathways is the BPM (between-pathway model) motif, introduced by Kelley
      and Ideker. Past methods proposed to search the yeast interactome for BPM motifs
      have had several important limitations. First, they have been driven
      heuristically by local greedy searches, which can lead to the inclusion of extra
      genes that may not belong in the motif; second, they have been validated solely
      by functional coherence of the putative pathways using GO enrichment, making it
      difficult to evaluate putative BPMs in the absence of already known biological
      annotation. We introduce stable bipartite subgraphs, and show they form a clean
      and efficient way of generating meaningful BPMs which naturally discard extra
      genes included by local greedy methods. We show by GO enrichment measures that
      our BPM set outperforms previous work, covering more known complexes and
      functional pathways. Perhaps most importantly, since our BPMs are initially
      generated by examining the genetic-interaction network only, the location of
      edges in the protein-protein physical interaction network can then be used to
      statistically validate each candidate BPM, even with sparse GO annotation (or
      none at all). We uncover some interesting biological examples of previously
      unknown putative redundant pathways in such areas as vesicle-mediated transport
      and DNA repair.

PMID- 19399175
TI  - Differential stress-induced neuronal activation patterns in mouse lines
      selectively bred for high, normal or low anxiety.
AB  - There is evidence for a disturbed perception and processing of emotional
      information in pathological anxiety. Using a rat model of trait anxiety generated
      by selective breeding, we previously revealed differences in challenge-induced
      neuronal activation in fear/anxiety-related brain areas between high (HAB) and
      low (LAB) anxiety rats. To confirm whether findings generalize to other species,
      we used the corresponding HAB/LAB mouse model and investigated c-Fos responses to
      elevated open arm exposure. Moreover, for the first time we included normal
      anxiety mice (NAB) for comparison. The results confirm that HAB mice show
      hyperanxious behavior compared to their LAB counterparts, with NAB mice
      displaying an intermediate anxiety phenotype. Open arm challenge revealed altered
      c-Fos response in prefrontal-cortical, limbic and hypothalamic areas in HAB mice
      as compared to LAB mice, and this was similar to the differences observed
      previously in the HAB/LAB rat lines. In mice, however, additional differential c
      Fos response was observed in subregions of the amygdala, hypothalamus, nucleus
      accumbens, midbrain and pons. Most of these differences were also seen between
      HAB and NAB mice, indicating that it is predominately the HAB line showing
      altered neuronal processing. Hypothalamic hypoactivation detected in LAB versus
      NAB mice may be associated with their low-anxiety/high-novelty-seeking phenotype.
      The detection of similarly disturbed activation patterns in a key set of anxiety
      related brain areas in two independent models reflecting psychopathological
      states of trait anxiety confirms the notion that the altered brain activation in
      HAB animals is indeed characteristic of enhanced (pathological) anxiety,
      providing information for potential targets of therapeutic intervention.

PMID- 19399176
TI  - Application of homozygosity haplotype analysis to genetic mapping with high
      density SNP genotype data.
AB  - BACKGROUND: In families segregating a monogenic genetic disorder with a single
      disease gene introduction, patients share a mutation-carrying chromosomal
      interval with identity-by-descent (IBD). Such a shared chromosomal interval or
      haplotype, surrounding the actual pathogenic mutation, is typically detected and
      defined by multipoint linkage and phased haplotype analysis using microsatellite
      or SNP genotype data. High-density SNP genotype data presents a computational
      challenge for conventional genetic analyses. A novel non-parametric method termed
      Homozygosity Haplotype (HH) was recently proposed for the genome-wide search of
      the autosomal segments shared among patients using high density SNP genotype
      data. METHODOLOGY/PRINCIPAL FINDINGS: The applicability and the effectiveness of
      HH in identifying the potential linkage of disease causative gene with high
      density SNP genotype data were studied with a series of monogenic disorders
      ascertained in eastern Canadian populations. The HH approach was validated using
      the genotypes of patients from a family affected with a rare autosomal dominant
      disease Schnyder crystalline corneal dystrophy. HH accurately detected the
      approximately 1 Mb genomic interval encompassing the causative gene UBIAD1 using
      the genotypes of only four affected subjects. The successful application of HH to
      identify the potential linkage for a family with pericentral retinal disorder
      indicates that HH can be applied to perform family-based association analysis by
      treating affected and unaffected family members as cases and controls
      respectively. A new strategy for the genome-wide screening of known causative
      genes or loci with HH was proposed, as shown the applications to a myoclonus
      dystonia and a renal failure cohort. CONCLUSIONS/SIGNIFICANCE: Our study of the
      HH approach demonstrates that HH is very efficient and effective in identifying
      potential disease linked region. HH has the potential to be used as an efficient
      alternative approach to sequencing or microsatellite-based fine mapping for
      screening the known causative genes in genetic disease study.

PMID- 19399177
TI  - The chromodomain of LIKE HETEROCHROMATIN PROTEIN 1 is essential for H3K27me3
      binding and function during Arabidopsis development.
AB  - Polycomb group (PcG) proteins are essential to maintain gene expression patterns
      during development. Transcriptional repression by PcG proteins involves
      trimethylation of H3K27 (H3K27me3) by Polycomb Repressive Complex 2 (PRC2) in
      animals and plants. PRC1 binds to H3K27me3 and is required for transcriptional
      repression in animals, but in plants PRC1-like activities have remained elusive.
      One candidate protein that could be involved in PRC1-like functions in plants is
      LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), because LHP1 associates with genes marked
      by H3K27me3 in vivo and has a chromodomain that binds H3K27me3 in vitro. Here, we
      show that disruption of the chromodomain of Arabidopsis thaliana LHP1 abolishes
      H3K27me3 recognition, releases gene silencing and causes similar phenotypic
      alterations as transcriptional lhp1 null mutants. Therefore, binding to H3K27me3
      is essential for LHP1 protein function.

PMID- 19399178
TI  - Efficient second strand cleavage during Holliday junction resolution by RuvC
      requires both increased junction flexibility and an exposed 5' phosphate.
AB  - BACKGROUND: Holliday junction (HJ) resolution is a critical step during
      homologous recombination. In Escherichia coli this job is performed by a member
      of the RNase H/Integrase superfamily called RuvC, whereas in Schizosaccharomyces
      pombe it has been attributed to the XPF family member Mus81-Eme1. HJ resolution
      is achieved through the sequential cleavage of two strands of like polarity at or
      close to the junction crossover point. RuvC functions as a dimer, whereas Mus81
      Eme1 is thought to function as a dimer of heterodimers. However, in both cases
      the multimer contains two catalytic sites, which act independently and
      sequentially during the resolution reaction. To ensure that both strands are
      cleaved before the nuclease dissociates from the junction, the rate of second
      strand cleavage is greatly enhanced compared to that of the first. The
      enhancement of second strand cleavage has been attributed to the increased
      flexibility of the nicked HJ, which would facilitate rapid engagement of the
      second active site and scissile bond. Here we have investigated whether other
      properties of the nicked HJ are important for enhancing second strand cleavage.
      PRINCIPAL FINDINGS: A comparison of the efficiency of cleavage of nicked HJs with
      and without a 5' phosphate at the nick site shows that a 5' phosphate is required
      for most of the enhancement of second strand cleavage by RuvC. In contrast Mus81
      Eme1 cleaves nicked HJs with and without a 5' phosphate with equal efficiency,
      albeit there are differences in cleavage site selection. CONCLUSIONS: Our data
      show that efficient HJ resolution by RuvC depends on the 5' phosphate revealed by
      incision of the first strand. This is a hitherto unappreciated factor in
      promoting accelerated second strand cleavage. However, a 5' phosphate is not a
      universal requirement since efficient cleavage by Mus81-Eme1 appears to depend
      solely on the increased junction flexibility that is developed by the first
      incision.

PMID- 19399179
TI  - Protective effect of geranylgeranylacetone via enhancement of HSPB8 induction in
      desmin-related cardiomyopathy.
AB  - BACKGROUND: An arg120gly (R120G) missense mutation in HSPB5 (alpha-beta
      crystallin ), which belongs to the small heat shock protein (HSP) family, causes
      desmin-related cardiomyopathy (DRM), a muscle disease that is characterized by
      the formation of inclusion bodies, which can contain pre-amyloid oligomer
      intermediates (amyloid oligomer). While we have shown that small HSPs can
      directly interrupt amyloid oligomer formation, the in vivo protective effects of
      the small HSPs on the development of DRM is still uncertain.
      METHODOLOGY/PRINCIPAL FINDINGS: In order to extend the previous in vitro findings
      to in vivo, we used geranylgeranylacetone (GGA), a potent HSP inducer. Oral
      administration of GGA resulted not only in up-regulation of the expression level
      of HSPB8 and HSPB1 in the heart of HSPB5 R120G transgenic (R120G TG) mice, but
      also reduced amyloid oligomer levels and aggregates. Furthermore, R120G TG mice
      treated with GGA exhibited decreased heart size and less interstitial fibrosis,
      as well as improved cardiac function and survival compared to untreated R120G TG
      mice. To address possible mechanism(s) for these beneficial effects, cardiac
      specific transgenic mice expressing HSPB8 were generated. Overexpression of HSPB8
      led to a reduction in amyloid oligomer and aggregate formation, resulting in
      improved cardiac function and survival. Treatment with GGA as well as the
      overexpression of HSPB8 also inhibited cytochrome c release from mitochondria,
      activation of caspase-3 and TUNEL-positive cardiomyocyte death in the R120G TG
      mice. CONCLUSIONS/SIGNIFICANCE: Expression of small HSPs such as HSPB8 and HSPB1
      by GGA may be a new therapeutic strategy for patients with DRM.

PMID- 19399180
TI  - BNP signaling is crucial for embryonic stem cell proliferation.
AB  - BACKGROUND: Embryonic stem (ES) cells have unlimited proliferation potential, and
      can differentiate into several cell types, which represent ideal sources for cell
      based therapy. This high-level proliferative ability is attributed to an unusual
      type of cell cycle. The Signaling pathways that regulate the proliferation of ES
      cells are of great interest. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we
      show that murine ES cells specifically express brain natriuretic peptide (BNP),
      and its signaling is essential for ES cell proliferation. We found that BNP and
      its receptor (NPR-A, natriuretic peptide receptor-A) were highly expressed in
      self-renewing murine ES cells, whereas the levels were markedly reduced after ES
      cell differentiation by the withdrawal of LIF. Targeting of BNP with short
      interfering RNA (siRNA) resulted in the inhibition of ES cell proliferation, as
      indicated by a marked reduction in the cell number and colony size, a significant
      reduction in DNA synthesis, and decreased numbers of cells in S phase. BNP
      knockdown in ES cells led to the up-regulation of gamma-aminobutyric acid
      receptor A (GABA(A)R) genes, and activation of phosphorylated histone (gamma
      H2AX), which negatively affects ES cell proliferation. In addition, knockdown of
      BNP increased the rate of apoptosis and reduced the expression of the
      transcription factor Ets-1. CONCLUSIONS/SIGNIFICANCE: Appropriate BNP expression
      is essential for the maintenance of ES cell propagation. These findings establish
      BNP as a novel endogenous regulator of ES cell proliferation.

PMID- 19399181
TI  - Wnt5a exhibits layer-specific expression in adult skin, is upregulated in
      psoriasis, and synergizes with type 1 interferon.
AB  - BACKGROUND: Wnt5a is a member of the wingless-type patterning regulators
      important in pre-natal development. The expression and distribution of Wnt5a and
      its receptors frizzled (fzd) 3 and fzd 5 in adult human skin have not been
      comprehensively studied to date. METHODOLOGY/PRINCIPAL FINDINGS: We here show
      that Wnt5a, fzd3, fzd5, as well as fzd6 are restricted to specific layers in
      normal epidermis, analogous to their zonal distribution in hair follicles,
      suggesting a role in adult skin differentiation. In line, Wnt5a and fzd5 are both
      overexpressed and re-distributed in the epidermis of psoriasis which involves
      disturbed keratinocyte differentiation. Functionally, Wnt5a lowers the
      concentration of IFN required to induce target genes, and increases the magnitude
      of IFN target gene induction, suggesting a molecular mechanism underlying IFN
      hypersensitivity in psoriasis. Finally, we identify nedd8 and the amyloid
      precursor APP, previously shown to be upregulated in psoriasis, as targets of
      synergistic IFNalpha/Wnt5a induction. CONCLUSIONS/SIGNIFICANCE: The present data
      (i) suggest that Wnt5a regulates epidermal differentiation even in adult skin and
      (ii) identify synergistic induction of type 1 IFN target genes as a novel mode of
      Wnt5a action. Targeting Wnt5a in the skin may reduce IFN hypersensitivity and be
      of therapeutical value.

PMID- 19399182
TI  - New microbicidal functions of tracheal glands: defective anti-infectious response
      to Pseudomonas aeruginosa in cystic fibrosis.
AB  - Tracheal glands (TG) may play a specific role in the pathogenesis of cystic
      fibrosis (CF), a disease due to mutations in the cftr gene and characterized by
      airway inflammation and Pseudomonas aeruginosa infection. We compared the gene
      expression of wild-type TG cells and TG cells with the cftr DeltaF508 mutation
      (CF-TG cells) using microarrays covering the whole human genome. In the absence
      of infection, CF-TG cells constitutively exhibited an inflammatory signature,
      including genes that encode molecules such as IL-1alpha, IL-beta, IL-32, TNFSF14,
      LIF, CXCL1 and PLAU. In response to P. aeruginosa, genes associated with IFN
      gamma response to infection (CXCL10, IL-24, IFNgammaR2) and other mediators of
      anti-infectious responses (CSF2, MMP1, MMP3, TLR2, S100 calcium-binding proteins
      A) were markedly up-regulated in wild-type TG cells. This microbicidal signature
      was silent in CF-TG cells. The deficiency of genes associated with IFN-gamma
      response was accompanied by the defective membrane expression of IFNgammaR2 and
      altered response of CF-TG cells to exogenous IFN-gamma. In addition, CF-TG cells
      were unable to secrete CXCL10, IL-24 and S100A8/S100A9 in response to P.
      aeruginosa. The differences between wild-type TG and CF-TG cells were due to the
      cftr mutation since gene expression was similar in wild-type TG cells and CF-TG
      cells transfected with a plasmid containing a functional cftr gene. Finally, we
      reported an altered sphingolipid metabolism in CF-TG cells, which may account for
      their inflammatory signature. This first comprehensive analysis of gene
      expression in TG cells proposes a protective role of wild-type TG against
      airborne pathogens and reveals an original program in which anti-infectious
      response was deficient in TG cells with a cftr mutation. This defective response
      may explain why host response does not contribute to protection against P.
      aeruginosa in CF.

PMID- 19399183
TI  - Protection by anti-beta-glucan antibodies is associated with restricted beta-1,3
      glucan binding specificity and inhibition of fungal growth and adherence.
AB  - Anti-beta-glucan antibodies elicited by a laminarin-conjugate vaccine confer
      cross-protection to mice challenged with major fungal pathogens such as Candida
      albicans, Aspergillus fumigatus and Cryptococcus neoformans. To gain insights
      into protective beta-glucan epitope(s) and protection mechanisms, we studied two
      anti-beta-glucan monoclonal antibodies (mAb) with identical complementarity
      determining regions but different isotypes (mAb 2G8, IgG2b and mAb 1E12, IgM). C.
      albicans, the most relevant fungal pathogen for humans, was used as a model.Both
      mAbs bound to fungal cell surface and to the beta1,3-beta1,6 glucan of the fungal
      cell wall skeleton, as shown by immunofluorescence, electron-microscopy and
      ELISA. They were also equally unable to opsonize fungal cells in a J774
      macrophage phagocytosis and killing assay. However, only the IgG2b conferred
      substantial protection against mucosal and systemic candidiasis in passive
      vaccination experiments in rodents. Competition ELISA and microarray analyses
      using sequence-defined glucan oligosaccharides showed that the protective IgG2b
      selectively bound to beta1,3-linked (laminarin-like) glucose sequences whereas
      the non-protective IgM bound to beta1,6- and beta1,4-linked glucose sequences in
      addition to beta1,3-linked ones. Only the protective IgG2b recognized
      heterogeneous, polydisperse high molecular weight cell wall and secretory
      components of the fungus, two of which were identified as the GPI-anchored cell
      wall proteins Als3 and Hyr1. In addition, only the IgG2b inhibited in vitro two
      critical virulence attributes of the fungus, hyphal growth and adherence to human
      epithelial cells.Our study demonstrates that the isotype of anti-beta-glucan
      antibodies may affect details of the beta-glucan epitopes recognized, and this
      may be associated with a differing ability to inhibit virulence attributes of the
      fungus and confer protection in vivo. Our data also suggest that the anti
      virulence properties of the IgG2b mAb may be linked to its capacity to recognize
      beta-glucan epitope(s) on some cell wall components that exert critical functions
      in fungal cell wall structure and adherence to host cells.

PMID- 19399184
TI  - t10c12 conjugated linoleic acid suppresses HER2 protein and enhances apoptosis in
      SKBr3 breast cancer cells: possible role of COX2.
AB  - BACKGROUND: HER2-targeted therapy with the monoclonal antibody trastuzumab
      (Herceptin) has improved disease-free survival for women diagnosed with HER2
      positive breast cancers; however, treatment resistance and disease progression
      are not uncommon. Current data suggest that resistance to treatment in HER2
      cancers may be a consequence of NF-kappaB overexpression and increased COX2
      derived prostaglandin E2 (PGE(2)). Conjugated linoleic acid (CLA) has been shown
      to have anti-tumor properties and to inhibit NF-kappaB activity and COX2.
      METHODS: In this study, HER2-overexpressing SKBr3 breast cancer cells were
      treated with t10c12 CLA. Protein expression of the HER2 receptor, nuclear NF
      kappaB p65, and total and phosphorylated IkappaB were examined by western blot
      and immunofluorescence. PGE(2) levels were determined by ELISA. Proliferation was
      measured by metabolism of 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium
      bromide (MTT), and apoptosis was measured by FITC-conjugated Annexin V staining
      and flow cytometry. RESULTS/CONCLUSIONS: We observed a significant decrease in
      HER2 protein expression on western blot following treatment with 40 and 80 microM
      t10c12 CLA (p<0.01 and 0.001, respectively) and loss of HER2 protein in cells
      using immunoflourescence that was most pronounced at 80 microM. Protein levels of
      nuclear NF-kappaB p65 were also significantly reduced at the 80 microM dose. This
      was accompanied by a significant decrease in PGE(2) levels (p = 0.05).
      Pretreatment with t10c12 CLA significantly enhanced TNFalpha-induced apoptosis
      and the anti-proliferative action of trastuzumab (p = 0.05 and 0.001,
      respectively). These data add to previous reports of an anti-tumor effect of
      t10c12 CLA and suggest an effect on the HER2 oncogene that may be through CLA
      mediated downregulation of COX2-derived PGE(2).

PMID- 19399185
TI  - Messina: a novel analysis tool to identify biologically relevant molecules in
      disease.
AB  - BACKGROUND: Morphologically similar cancers display heterogeneous patterns of
      molecular aberrations and follow substantially different clinical courses. This
      diversity has become the basis for the definition of molecular phenotypes, with
      significant implications for therapy. Microarray or proteomic expression
      profiling is conventionally employed to identify disease-associated genes,
      however, traditional approaches for the analysis of profiling experiments may
      miss molecular aberrations which define biologically relevant subtypes.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can
      identify those genes that only sometimes show aberrant expression in cancer. We
      demonstrate with simulated data that Messina is highly sensitive and specific
      when used to identify genes which are aberrantly expressed in only a proportion
      of cancers, and compare Messina to contemporary analysis techniques. We
      illustrate Messina by using it to detect the aberrant expression of a gene that
      may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE:
      Messina allows the detection of genes with profiles typical of markers of
      molecular subtype, and complements existing methods to assist the identification
      of such markers. Messina is applicable to any global expression profiling data,
      and to allow its easy application has been packaged into a freely-available stand
      alone software package.

PMID- 19399186
TI  - Betulin is a potent anti-tumor agent that is enhanced by cholesterol.
AB  - Betulinic Acid (BetA) and its derivatives have been extensively studied in the
      past for their anti-tumor effects, but relatively little is known about its
      precursor Betulin (BE). We found that BE induces apoptosis utilizing a similar
      mechanism as BetA and is prevented by cyclosporin A (CsA). BE induces cell death
      more rapidly as compared to BetA, but to achieve similar amounts of cell death a
      considerably higher concentration of BE is needed. Interestingly, we observed
      that cholesterol sensitized cells to BE-induced apoptosis, while there was no
      effect of cholesterol when combined with BetA. Despite the significantly enhanced
      cytotoxicity, the mode of cell death was not changed as CsA completely abrogated
      cell death. These results indicate that BE has potent anti-tumor activity
      especially in combination with cholesterol.

PMID- 19399187
TI  - Neurodevelopment genes in lampreys reveal trends for forebrain evolution in
      craniates.
AB  - The forebrain is the brain region which has undergone the most dramatic changes
      through vertebrate evolution. Analyses conducted in lampreys are essential to
      gain insight into the broad ancestral characteristics of the forebrain at the
      dawn of vertebrates, and to understand the molecular basis for the
      diversifications that have taken place in cyclostomes and gnathostomes following
      their splitting. Here, we report the embryonic expression patterns of 43 lamprey
      genes, coding for transcription factors or signaling molecules known to be
      involved in cell proliferation, stemcellness, neurogenesis, patterning and
      regionalization in the developing forebrain. Systematic expression patterns
      comparisons with model organisms highlight conservations likely to reflect shared
      features present in the vertebrate ancestors. They also point to changes in
      signaling systems -pathways which control the growth and patterning of the
      neuroepithelium-, which may have been crucial in the evolution of forebrain
      anatomy at the origin of vertebrates.

PMID- 19399188
TI  - A novel triterpenoid isolated from the root bark of Ailanthus excelsa Roxb (Tree
      of Heaven), AECHL-1 as a potential anti-cancer agent.
AB  - BACKGROUND: We report here the isolation and characterization of a new compound
      Ailanthus excelsa chloroform extract-1 (AECHL-1) (C(29)H(36)O(10); molecular
      weight 543.8) from the root bark of Ailanthus excelsa Roxb. The compound
      possesses anti-cancer activity against a variety of cancer cell lines of
      different origin. PRINCIPAL FINDINGS: AECHL-1 treatment for 12 to 48 hr inhibited
      cell proliferation and induced death in B16F10, MDA-MB-231, MCF-7, and PC3 cells
      with minimum growth inhibition in normal HEK 293. The antitumor effect of AECHL-1
      was comparable with that of the conventional antitumor drugs paclitaxel and
      cisplatin. AECHL-1-induced growth inhibition was associated with S/G(2)-M arrests
      in MDA-MB-231, MCF-7, and PC3 cells and a G(1) arrest in B16F10 cells. We
      observed microtubule disruption in MCF-7 cells treated with AECHL-1 in vitro.
      Compared with control, subcutaneous injection of AECHL-1 to the sites of tumor of
      mouse melanoma B16F10 implanted in C57BL/6 mice and human breast cancer MCF-7
      cells in athymic nude mice resulted in significant decrease in tumor volume. In
      B16F10 tumors, AECHL-1 at 50 microg/mouse/day dose for 15 days resulted in
      increased expression of tumor suppressor proteins P53/p21, reduction in the
      expression of the oncogene c-Myc, and downregulation of cyclin D1 and cdk4.
      Additionally, AECHL-1 treatment resulted in the phosphorylation of p53 at serine
      15 in B16F10 tumors, which seems to exhibit p53-dependent growth inhibitory
      responses. CONCLUSIONS: The present data demonstrate the activity of a
      triterpenoid AECHL-1 which possess a broad spectrum of activity against cancer
      cells. We propose here that AECHL-1 is a futuristic anti-cancer drug whose
      therapeutic potential needs to be widely explored for chemotherapy against
      cancer.

PMID- 19399189
TI  - CTIP2 expression in human head and neck squamous cell carcinoma is linked to
      poorly differentiated tumor status.
AB  - BACKGROUND: We have demonstrated earlier that CTIP2 is highly expressed in mouse
      skin during embryogenesis and in adulthood. CTIP2 mutant mice die at birth with
      epidermal differentiation defects and a compromised epidermal permeability
      barrier suggesting its role in skin development and/or homeostasis. CTIP2 has
      also been suggested to function as tumor suppressor in cells, and several reports
      have described a link between chromosomal rearrangements of CTIP2 and human T
      cell acute lymphoblast leukemia (T-ALL). The aim of the present study was to look
      into the pattern of CTIP2 expression in Head and Neck Squamous Cell Carcinoma
      (HNSCC). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we analyzed CTIP2
      expression in human HNSCC cell lines by western blotting, in paraffin embedded
      archival specimens by immunohistochemistry (IHC), and in cDNA samples of human
      HNSCC by qRT-PCR. Elevated levels of CTIP2 protein was detected in several HNSCC
      cell lines. CTIP2 staining was mainly detected in the basal layer of the head and
      neck normal epithelium. CTIP2 expression was found to be significantly elevated
      in HNSCC (p<0.01), and increase in CTIP2 expression was associated with poorly
      differentiated tumor status. Nuclear co-localization of CTIP2 protein and cancer
      stem cell (CSC) marker BMI1 was observed in most, if not all of the cells
      expressing BMI1 in moderately and poorly differentiated tumors.
      CONCLUSIONS/SIGNIFICANCE: We report for the first time expression of
      transcriptional regulator CTIP2 in normal human head and neck epithelia. A
      statistically significant increase in the expression of CTIP2 was detected in the
      poorly differentiated samples of the human head and neck tumors. Actual CTIP2,
      rather than the long form of CTIP2 (CTIP2(L)) was found to be more relevant to
      the differentiation state of the tumors. Results demonstrated existence of
      distinct subsets of cancer cells, which express CTIP2 and underscores the use of
      CTIP2 and BMI1 co-labeling to distinguish tumor initiating cells or cancer stem
      cells (CSCs) from surrounding cancer cells.

PMID- 19399190
TI  - A single nucleotide change affects fur-dependent regulation of sodB in H. pylori.
AB  - Helicobacter pylori is a significant human pathogen that has adapted to survive
      the many stresses found within the gastric environment. Superoxide Dismutase
      (SodB) is an important factor that helps H. pylori combat oxidative stress. sodB
      was previously shown to be repressed by the Ferric Uptake Regulator (Fur) in the
      absence of iron (apo-Fur regulation) [1]. Herein, we show that apo regulation is
      not fully conserved among all strains of H. pylori. apo-Fur dependent changes in
      sodB expression are not observed under iron deplete conditions in H. pylori
      strains G27, HPAG1, or J99. However, Fur regulation of pfr and amiE occurs as
      expected. Comparative analysis of the Fur coding sequence between G27 and 26695
      revealed a single amino acid difference, which was not responsible for the
      altered sodB regulation. Comparison of the sodB promoters from G27 and 26695 also
      revealed a single nucleotide difference within the predicted Fur binding site.
      Alteration of this nucleotide in G27 to that of 26695 restored apo-Fur dependent
      sodB regulation, indicating that a single base difference is at least partially
      responsible for the difference in sodB regulation observed among these H. pylori
      strains. Fur binding studies revealed that alteration of this single nucleotide
      in G27 increased the affinity of Fur for the sodB promoter. Additionally, the
      single base change in G27 enabled the sodB promoter to bind to apo-Fur with
      affinities similar to the 26695 sodB promoter. Taken together these data indicate
      that this nucleotide residue is important for direct apo-Fur binding to the sodB
      promoter.

PMID- 19399192
TI  - Forming an intracorporeal slip-knot in laparoscopic suturing.

PMID- 19399193
TI  - Giant symptomatic adrenal cyst in a patient with an ectopic kidney.

PMID- 19399191
TI  - In vitro germ cell differentiation from cynomolgus monkey embryonic stem cells.
AB  - BACKGROUND: Mouse embryonic stem (ES) cells can differentiate into female and
      male germ cells in vitro. Primate ES cells can also differentiate into immature
      germ cells in vitro. However, little is known about the differentiation markers
      and culture conditions for in vitro germ cell differentiation from ES cells in
      primates. Monkey ES cells are thus considered to be a useful model to study
      primate gametogenesis in vitro. Therefore, in order to obtain further information
      on germ cell differentiation from primate ES cells, this study examined the
      ability of cynomolgus monkey ES cells to differentiate into germ cells in vitro.
      METHODS AND FINDINGS: To explore the differentiation markers for detecting germ
      cells differentiated from ES cells, the expression of various germ cell marker
      genes was examined in tissues and ES cells of the cynomolgus monkey (Macaca
      fascicularis). VASA is a valuable gene for the detection of germ cells
      differentiated from ES cells. An increase of VASA expression was observed when
      differentiation was induced in ES cells via embryoid body (EB) formation. In
      addition, the expression of other germ cell markers, such as NANOS and PIWIL1
      genes, was also up-regulated as the EB differentiation progressed.
      Immunocytochemistry identified the cells expressing stage-specific embryonic
      antigen (SSEA) 1, OCT-4, and VASA proteins in the EBs. These cells were detected
      in the peripheral region of the EBs as specific cell populations, such as SSEA1
      positive, OCT-4-positive cells, OCT-4-positive, VASA-positive cells, and OCT-4
      negative, VASA-positive cells. Thereafter, the effect of mouse gonadal cell
      conditioned medium and growth factors on germ cell differentiation from monkey ES
      cells was examined, and this revealed that the addition of BMP4 to
      differentiating ES cells increased the expression of SCP1, a meiotic marker gene.
      CONCLUSION: VASA is a valuable gene for the detection of germ cells
      differentiated from ES cells in monkeys, and the identification and
      characterization of germ cells derived from ES cells are possible by using
      reported germ cell markers in vivo, including SSEA1, OCT-4, and VASA, in vitro as
      well as in vivo. These findings are thus considered to help elucidate the germ
      cell developmental process in primates.

PMID- 19399194
TI  - Duodenal gangliocytic paraganglioma.

PMID- 19399195
TI  - Inguinoscrotal extraperitoneal herniation of a ureter.

PMID- 19399196
TI  - Carcinoma of the sigmoid colon in an incarcerated inguinal hernia.

PMID- 19399197
TI  - Myositis ossificans traumatica of the abdominal wall.

PMID- 19399198
TI  - Protein C deficiency and mesenteric venous thrombosis.

PMID- 19399199
TI  - Pigmented villonodular synovitis in both hindfeet.

PMID- 19399201
TI  - Dedicated orthopedic trauma theatres: effect on morbidity and mortality in a
      single trauma centre.
AB  - BACKGROUND: A general trend in orthopedic traumatology is the advent of daily,
      dedicated orthopedic trauma theatres. Availability of trauma theatres is believed
      to decrease morbidity and mortality, but this remains unproven. We performed a
      retrospective review comparing morbidity and mortality outcomes at a single
      institution before and after the establishment of a dedicated trauma room. The
      purpose was to determine whether a change in outcomes occurred for a single
      routine procedure with known outcome expectations (hemiarthroplasty of the hip
      after femoral neck fracture) with the implementation of a designated trauma
      theatre. METHODS: We examined a cohort of 457 elderly patients (245 before and
      212 after trauma theatre implementation) who underwent hemiarthroplasty for
      displaced low-energy subcapital hip fractures. RESULTS: Patients in both groups
      were similar in terms of age, sex ratio and ASA classification. We found
      statistically significant differences favouring the dedicated trauma room system
      for postoperative morbidity. Despite this outcome, the average time to surgery
      for these patients significantly increased. We noted no difference in mortality
      between the 2 groups. CONCLUSION: The hip fracture population can be treated
      safely in the context of dedicated trauma room time; however, there needs to be
      prioritization of hip fractures in a tertiary care centre or other trauma cases
      will tend to take precedence.

PMID- 19399202
TI  - Concordance with clinical practice guidelines for adjuvant chemotherapy in
      patients with stage I-III colon cancer: experience in 2 Canadian provinces.
AB  - BACKGROUND: Clinical practice guidelines (CPGs) for the adjuvant treatment of
      colorectal cancer were published by the National Institutes of Health in 1991.
      The American Society of Clinical Oncology and Cancer Care Ontario have
      recommended adjuvant chemotherapy for patients with high-risk stage II colon
      cancer. We evaluated differences in concordance with guidelines in the treatment
      of patients with stage I-III colon cancer in the Canadian provinces of
      Newfoundland and Labrador and Ontario. METHODS: We assessed clinical data and
      treatment from January 1999 to December 2000 for 130 patients from Newfoundland
      and Labrador and 315 patients from Ontario who had stage I-III colon cancer. The
      primary outcome was concordance with guidelines for adjuvant treatment. We
      evaluated factors affecting the use of chemotherapy in patients with stage II
      disease. RESULTS: No patients received adjuvant therapy for stage I disease.
      Forty-five of 52 patients (87%) in Newfoundland and Labrador and 108 of 115
      patients (94%) in Ontario received adjuvant chemotherapy for stage III colon
      cancer. Twenty of 55 patients (36%) in Newfoundland and Labrador and 44 of 116
      patients (38%) in Ontario received adjuvant therapy for stage II disease.
      Eighteen of 41 patients (44%) in Newfoundland and Labrador and 30 of 53 patients
      (57%) in Ontario with high-risk features received adjuvant treatment, which was
      significantly higher than patients without high-risk features. There was a strong
      trend toward using chemotherapy in patients with stage II disease who were 50
      years or younger, independent of high-risk status. CONCLUSION: Concordance with
      CPGs for adjuvant chemotherapy in patients with stage II colon cancer was not
      optimal. This may reflect selection bias among referring surgeons, a paucity of
      level-I evidence and the belief that other factors such as age may play a role in
      predicting outcome.

PMID- 19399203
TI  - Outcome errors are not necessary for learning orthopedic bone drilling.
AB  - BACKGROUND: When learning orthopedic bone drilling, a surgical trainee relies on
      internally generated and externally provided feedback. The quality and type of
      feedback often varies in the clinical environment, thus affecting skill
      acquisition. We investigated the effect of feedback on technical error (plunging)
      when novice surgical trainees learned bone drilling. METHODS: Medical students (n
      = 22) and experienced postgraduate surgical residents (n = 4) drilled bicortical
      holes in a lamb femur under 1 of 3 feedback conditions: no feedback, self
      generated feedback and externally generated feedback. Novices performed a
      retention test (10 bicortical holes) 1 week after the initial training. We
      measured plunge depth, the clinically relevant outcome, using computer-assisted
      methods. RESULTS: During the initial experiment, the plunges of novices who were
      exposed to external feedback were similar to those of residents in the
      experienced group. Novices in the self-generated feedback group plunged more than
      those in the external feedback group or those in the experienced group (p =
      0.002). All novices plunged similarly on the retention test, a measure of true
      skill learning. CONCLUSION: When learning bicortical bone drilling, feedback
      related to plunging is not necessary to achieve a competent level of performance.
      In addition, although external feedback facilitates the achievement of better
      outcomes, it does not improve learning. It is suggested that to minimize
      plunging, trainees should learn how to optimize their drilling through the bone
      rather than how to prevent the plunge.

PMID- 19399204
TI  - Distraction osteogenesis technique using an intramedullary nail and a monolateral
      external fixator in the reconstruction of massive postosteomyelitis skeletal
      defects of the femur.
AB  - BACKGROUND: Large skeletal defects due to postosteomyelitis are uncommon, and
      they present a challenging reconstructive problem. The aim of our study was to
      summarize our experience performing a distraction osteogenesis technique using an
      intramedullary nail and a monolateral external fixator in the reconstruction of
      massive postosteomyelitis skeletal defects of the femur. METHODS: Between January
      1998 and October 2004, 17 patients with massive postosteomyelitis skeletal
      defects of the femur (11 men and 6 women), underwent the reconstruction
      procedure. After osteotomy of diaphysis of the femur, we inserted an
      intramedullary nail into the femur, and we placed a monolateral external fixator
      with half-pins lateral to the nail. Lengthening was started on the seventh
      postoperative day at a rate of 1 mm/d. Once we achieved solid bone union, we
      removed the monolateral external fixator; the intramedullary nail remained for
      bone consolidation until reconsruction was complete. We assessed the outcomes
      clinically and radiographically at a mean of 70.3 months postoperatively.
      RESULTS: At follow-up (mean 70.3, range 14.0-96.0 mo), all the skeletal defects
      were filled, bone union at docking sites was achieved without bone graft and leg
      length discrepancies were less than 2.5 cm in all patients. The mean gain in
      length was 12.9 (range 10.2-18.4) cm. According to Paley and Maar's evaluation
      criteria, we graded the bone results as excellent for 10 patients, good for 5,
      fair for 1 and poor for 1. We graded the functional results as excellent for 12
      patients, good for 4 and fair for 1. The mean external fixator index was 18.1
      d/cm; the consolidation index was 35.7 d/cm. Ten patients experienced pin
      infection, and 1 patient experienced a recurrence of deep infection. There were
      no neurologic or vascular injuries. CONCLUSION: Our study demonstrates that a
      distraction osteogenesis technique using an intramedullary nail and a monolateral
      external fixator is a reliable method for the reconstruction of massive
      postosteomyelitis skeletal defects.

PMID- 19399205
TI  - Chronic volar distal radioulnar joint instability: joint capsular plication to
      restore function.
AB  - BACKGROUND: Volar instability of the distal radioulnar joint (DRUJ) is uncommon,
      and there is little written about it. The purpose of this study is to describe a
      new procedure to treat volar DRUJ instability and to present the outcomes of
      patients who received this unique surgical repair at a minimum of 1 year follow
      up. METHODS: We performed a retrospective case series of 6 consecutive patients
      treated with a volar and dorsal capsular plication procedure by an upper
      extremity specialist surgeon at a teaching hospital between April 1999 and
      October 2004. We evaluated measures, including wrist range of motion, grip
      strength, radiographs, Disabilities of the Arm, Shoulder and Hand (DASH)
      questionnaire and Patient-Rated Wrist Evaluation (PRWE), at final follow-up.
      RESULTS: Five of 6 patients had resolution of pain and instability symptoms. The
      average difference in range of motion between operative and contralateral sides
      was -7 degrees flexion, 2 degrees extension, 4 degrees radial deviation, 2
      degrees ulnar deviation, -17 degrees supination and -2 degrees pronation. Average
      grip strength measured 83% of the uninjured side. The average DASH score was 13.5
      (range 0-46.7), and the average PRWE score was 26.7 (range 0-70). One patient had
      a low ulnar neuropathy, which resolved. One patient fractured the temporary DRUJ
      stabilization screw and had radiographic evidence of nonbridging heterotopic
      ossification. CONCLUSION: Joint capsular plication for DRUJ has not yet been
      described in the literature. It is less elaborate in that it does not require a
      tendon graft with bone tunnels. The results at an average 16.5 months
      postoperatively are promising.

PMID- 19399206
TI  - Incidence and impact of dysphagia in patients receiving prolonged endotracheal
      intubation after cardiac surgery.
AB  - BACKGROUND: Cardiac surgery is frequently associated with prolonged endotracheal
      intubation. Because oral feeding is an important component of patient recovery
      after high-risk surgery, we sought to examine the contribution of dysphagia in
      the recuperation process after prolonged endotracheal intubation. METHODS: All
      254 adult patients who survived cardiac surgery between 2001 and 2004 at the
      Toronto General Hospital and in whom endotracheal intubation lasted for 48 hours
      or longer were eligible for our retrospective review. We used multivariate
      regression analysis and parametric modelling to identify patient-specific
      characteristics associated with postextubation dysphagia and the subsequent
      resumption of normal oral feeding. RESULTS: Dysphagia was diagnosed in 130 (51%)
      patients. Incremental factors associated with an increased risk for
      postextubation dysphagia included duration of endotracheal intubation (p <
      0.001), the occurrence of a perioperative cerebrovascular event (p = 0.014) and
      the presence of perioperative sepsis (p = 0.016). Neither preoperative patient
      risks nor index procedural characteristics were influential factors. The
      occurrence of dysphagia (p < 0.001) and the duration of endotracheal intubation
      (p < 0.001) were the only independent factors associated with a delayed return to
      normal oral feeding. In contrast, several independent factors were associated
      with a delay to hospital discharge, including the presence of dysphagia (p <
      0.001), occurrence of perioperative stroke (p < 0.001), duration of endotracheal
      intubation (p < 0.001) and number of endotracheal intubation events (p < 0.006).
      CONCLUSION: Dysphagia is more common in patients with prolonged endotracheal
      intubation after cardiac surgery than has previously been reported. The duration
      of postoperative endotracheal intubation is a strong predictor of subsequent
      dysphagia that both prolongs the return to normal oral feeding and delays
      subsequent hospital discharge. Patient-or procedure-specific factors are not good
      predictors. To accelerate discharge of high-risk patients, aggressive nutritional
      supplementation should pre-empt extubation and swallowing surveillance should
      follow.

PMID- 19399207
TI  - Comparison of gastrointestinal complications in on-pump versus off-pump coronary
      artery bypass grafting.
AB  - BACKGROUND: Gastrointestinal (GI) complications following coronary artery bypass
      grafting (CABG), although infrequent, are associated with significant morbidity
      and mortality. It has been suggested that systemic inflammatory response plays an
      important role in these complications. Cardiopulmonary bypass (CPB) is well known
      to cause increased systemic inflammation, and therefore it has been proposed that
      performing CABG using an off-pump technique could substantially minimize the risk
      of GI complications. Prolonged CPB duration has been shown to be an independent
      predictor of GI complications; however, the effect of avoiding CPB altogether
      through off-pump procedures has not been thoroughly examined. We sought to
      compare the incidence of GI complications in patients undergoing on-pump and off
      pump CABG. METHODS: We analyzed prospectively entered data on 2451 patients who
      underwent isolated CABG between January 2000 and October 2004. We compared GI
      complication rates in 5 predetermined areas (GI bleed, ileus, pancreatitis,
      ischemic bowel and cholecystitis) among patients who had on-pump CABG with those
      of patients who had off-pump CABG. We also compared in-hospital mortality due to
      these complications between the 2 groups. RESULTS: We compared data for a total
      of 2010 patients in the on-pump group and 441 in the off-pump group. In the on
      pump group, 30 (1.49%) patients experienced GI complications compared with 4
      (0.91%) in the off-pump group (p = 0.34). Gastrointestinal bleed was the most
      common complication in the off-pump group. Eight patients in the on-pump group
      experienced ischemic bowels compared with no patients in the off-pump group. Six
      patients (0.3%) in the on-pump group died from GI complications, whereas no
      patients in the off-pump group died from such complications (p = 0.25).
      CONCLUSION: We found no significant difference in the total number of GI
      complications between the off-pump and on-pump groups; however, trends could be
      seen in the types of GI complications that occurred in the 2 groups. Owing to the
      relatively infrequent occurrence of GI complications, a larger scale study would
      be beneficial to determine whether the differences observed would be significant.

PMID- 19399208
TI  - Needlescopic versus laparoscopic appendectomy: a systematic review.
AB  - BACKGROUND: Needlescopic appendectomies (NA) have been performed since the 1990s.
      We sought to systematically analyze trials comparing NA with laparoscopic
      appendectomies (LA) in the management of appendicitis. METHODS: We performed a
      systematic review of the literature. We compared and analyzed clinical trials on
      NA and LA to generate summative data expressed as standardized mean differences
      (SMD). RESULTS: Of 5 retrieved trials from the electronic database 2 trials
      involving 412 patients met our inclusion criteria. In the fixed-effects models,
      NA took longer than LA, and this time difference was statistically significant:
      SMD 0.20 min, 95% confidence interval 0.01-0.40, p = 0.030, z(1) = 2.09. In both
      fixed-and random-effects models, the difference in total hospital stay and in
      perioperative complications between the NA and LA groups were nonsignificant.
      Furthermore, in both fixed-and random-effects models, NA was associated with a
      higher conversion rate to open appendectomy than LA. There was no heterogeneity
      between the trials (Q = 0.34, p = 0.55). CONCLUSION: Needlescopic appendectomy
      can be a safe and effective procedure for the management of appendicitis. It is
      comparable to LA in terms of hospital stay and perioperative complications.
      However, NA is associated with a longer duration of surgery and a higher
      conversion rate, indicating technical challenges of the procedure. Before
      recommending routine use of the needlescopic technique for appendectomy, a major
      multicentre randomized controlled trial is necessary.

PMID- 19399209
TI  - Surgical cytoreduction and intraperitoneal chemotherapy for peritoneal
      carcinomatosis arising from the appendix.
AB  - BACKGROUND: Peritoneal carcinomatosis (PC) originating in the appendix is a rare
      disease for which the long-term prognosis is poor. The aim of our study was to
      evaluate the results of an aggressive treatment approach used in our institution
      in the last decade. METHODS: We prospectively collected and analyzed data from
      all patients with PC. Treatment consisted of complete surgical cytoreduction of
      the tumour followed by intraperitoneal chemotherapy. Chemotherapy was either
      early postoperative intraperitoneal chemotherapy (EPIC) or hyperthermic
      intraperitoneal chemotherapy (HIPEC). We used Ronnett's classification for tumour
      grading (disseminated peritoneal adenomucinosis = grade 0, peritoneal mucinous
      carcinomatosis with intermediate features = grade 1 and peritoneal mucinous
      carcinomatosis = grade 2). RESULTS: From September 1997 to June 2005, 37 patients
      underwent laparotomy with curative intent; 13 received EPIC and 11 HIPEC.
      Thirteen patients could not have complete cytoreductive surgery and received no
      intraperitoneal chemotherapy. The estimated 5-year overall survival was 56% (95%
      confidence interval [CI] 34%-77%) for all patients, 58% (95% CI 30%-86%) for
      patients who underwent EPIC and 60% (95% CI 10%-100%) for patients who underwent
      HIPEC (p = 0.97). Histologic grade was an important prognostic indicator as all
      patients with grade 0 tumours survived whereas no patients with grade 2 tumours
      survived (p < 0.001). Patients with grade 1 tumours had an estimated 87% (95% CI
      64%-100%) 5-year overall survival. There was no mortality attributed to surgery.
      The overall complication rate was 36%, including fistulas (16%), intra-abdominal
      abscesses (12%) and hemorrhage (9%). CONCLUSION: This therapeutic approach seems
      both feasible and safe in select patients. Patients with high-grade tumours are
      poor candidates for this treatment.

PMID- 19399210
TI  - Employment status and personal characteristics in patients awaiting hip
      replacement surgery.
AB  - BACKGROUND: Total hip arthroplasty (THA) is a cost-effective surgical
      intervention that substantially improves quality of life. Recent advances have
      broadened the indications to include younger, working-age patients. Despite these
      benefits, there are often long waits for this procedure in Canada. Furthermore,
      there exists little documentation of the ability of patients waiting for THA to
      maintain employment or perform their occupational duties. METHODS: I
      prospectively identified patients younger than 65 years from a primary hip
      replacement surgery waiting list. The study coordinator contacted patients by
      phone and asked them to participate; if they agreed, we mailed them a validated
      questionnaire. To compare working with nonworking patients, I used univariate
      analysis and logistic regression modeling. RESULTS: A total of 84 of the 100
      patients who agreed to participate returned the questionnaire. While awaiting
      THA, 20% of patients who considered themselves to be in the workforce were off
      work owing to their hip conditions. Work cessation resulted in a median drop in
      income of $15,000 CDN and forgone tax revenues of $3800. Poor hip function was
      related to both lowered productivity and work cessation before surgery. Patients
      with an Oxford 12 hip score of 50 or worse appeared to have about a 50% chance of
      stopping work before THA, whereas those with a score of 40 or better appeared to
      have only a 10% chance of stopping work. CONCLUSION: About 20% of patients in the
      workforce who are awaiting THA are off work owing to their hip conditions while
      on the waiting list. Poor hip function is associated with work cessation and
      decreased productivity.

PMID- 19399211
TI  - Radiation dose from initial trauma assessment and resuscitation: review of the
      literature.
AB  - BACKGROUND: Trauma care benefits from the use of imaging technologies. Trauma
      patients and trauma team members are exposed to radiation during the continuum of
      care. Knowledge of exposure amounts and effects are important for trauma team
      members. METHODS: We performed a review of the published literature; keywords
      included "trauma," "patients," "trauma team members," "wounds," "injuries,"
      "radiation," "exposure," "dose" and "computed tomography" (CT). We also reviewed
      the Board on Radiation Effects Research (BEIR VII) report, published in 2005 and
      2006. RESULTS: We found no randomized controlled trials or studies. Relevant
      studies demonstrated that CT accounts for the single largest radiation exposure
      in trauma patients. Exposure to 100 mSv could result in a solid organ cancer or
      leukemia in 1 of 100 people. Trauma team members do not exceed the acceptable
      occupation radiation exposure determined by the National Council of Radiation
      Protection and Management. Modern imaging technologies such as 16- and 64-slice
      CT scanners may decrease radiation exposure. CONCLUSION: Multiple injured trauma
      patients receive a substantial dose of radiation. Radiation exposure is
      cumulative. The low individual risk of cancer becomes a greater public health
      issue when multiplied by a large number of examinations. Though CT scans are an
      invaluable resource and are becoming more easily accessible, they should not
      replace careful clinical examination and should be used only in appropriate
      patients.

PMID- 19399212
TI  - Pharmacological management of postoperative ileus.
AB  - The duration of postoperative ileus following abdominal surgery is quite
      variable, and prolonged postoperative ileus is an iatrogenic phenomenon with
      important influence on patient morbidity, hospital costs and length of stay in
      hospital. Adequate treatment for prolonged postoperative ileus is important to
      improve patient morbidity and clinical efficiency. Both clinical and
      pharmacological management strategies have improved rapidly over the last decade,
      and appropriate and timely management using multimodal techniques should be used
      for optimal care. In this review, we define postoperative ileus, describe the
      pathogenesis and briefly discuss clinical management before detailing potential
      pharmacologic management options.

PMID- 19399213
TI  - Mucinous cystadenoma of the appendix.

PMID- 19399214
TI  - Dermatoses of the nipple.

PMID- 19399217
TI  - Preoperative and perioperative management of patients with suspected lung cancer.

PMID- 19399219
TI  - Formation versus hydrolysis of the peptide bond from a quantum-mechanical
      viewpoint: The role of mineral surfaces and implications for the origin of life.
AB  - The condensation (polymerization by water elimination) of molecular building
      blocks to yield the first active biopolymers (e.g. of amino acids to form
      peptides) during primitive Earth is an intriguing question that nowadays still
      remains open since these processes are thermodynamically disfavoured in highly
      dilute water solutions. In the present contribution, formation and hydrolysis of
      glycine oligopeptides occurring on a cluster model of sanidine feldspar (001)
      surface have been simulated by quantum mechanical methods. Results indicate that
      the catalytic interplay between Lewis and Bronsted sites both present at the
      sanidine surface, in cooperation with the London forces acting between the
      biomolecules and the inorganic surface, plays a crucial role to: i) favour the
      condensation of glycine to yield oligopeptides as reaction products; ii) inhibit
      the hydrolysis of the newly formed oligopeptides. Both facts suggest that mineral
      surfaces may have helped in catalyzing, stabilizing and protecting from hydration
      the oligopeptides formed in the prebiotic era.

PMID- 19399218
TI  - Molecular pathology of Lewy body diseases.
AB  - Lewy body diseases are characterized by the presence of Lewy bodies, alpha
      synuclein(AS)-positive inclusions in the brain. Since their main component is
      conformationally modified AS, aggregation of the latter is thought to be a key
      pathogenic event in these diseases. The analysis of inclusion body constituents
      gives additional information about pathways also involved in the pathology of
      synucleinopathies. Widespread mitochondrial dysfunction is very closely related
      to disease development. The impairment of protein degradation pathways, including
      both the ubiquitin-proteasome system and the autophagy-lysosome pathway also play
      an important role during the development of Lewy body diseases. Finally,
      differential expression changes of isoforms corresponding to genes primarily
      involved in Lewy body formation point to alternative splicing as another
      important mechanism in the development of Parkinson's disease, as well as
      dementia with Lewy bodies. The present paper attempts to give an overview of
      recent molecular findings related to the pathogenesis of Lewy body diseases.

PMID- 19399220
TI  - An algorithm for emulsion stability simulations: account of flocculation,
      coalescence, surfactant adsorption and the process of Ostwald ripening.
AB  - The first algorithm for Emulsion Stability Simulations (ESS) was presented at the
      V Conferencia Iberoamericana sobre Equilibrio de Fases y Diseno de Procesos
      [Luis, J.; Garcia-Sucre, M.; Urbina-Villalba, G. Brownian Dynamics Simulation of
      Emulsion Stability In: Equifase 99. Libro de Actas, 1(st) Ed., Tojo J., Arce, A.,
      Eds.; Solucion's: Vigo, Spain, 1999; Volume 2, pp. 364-369]. The former version
      of the program consisted on a minor modification of the Brownian Dynamics
      algorithm to account for the coalescence of drops. The present version of the
      program contains elaborate routines for time-dependent surfactant adsorption,
      average diffusion constants, and Ostwald ripening.

PMID- 19399221
TI  - Ordering and reverse ordering mechanisms of triblock copolymers in the presence
      of solvent.
AB  - Self-consistent field theory is used to study the self-assembly of a triblock
      copolymer melt. Two different external factors (temperature and solvent) are
      shown to affect the self-assembly. Either one or two-step self-assembly can be
      found as a function of temperature in the case of a neat triblock melt, or as a
      function of increasing solvent content (for non-selective solvents) in the case
      of a triblock-solvent mixture. For selective solvents, it is shown that
      increasing the solvent content leads to more complicated self-assembly
      mechanisms, including a reversed transition where order is found to increase
      instead of decreasing as expected, and re-entrant behavior where order is found
      to increase at first, and then decrease to a previous state of disorder.

PMID- 19399222
TI  - The role of disordered ribosomal protein extensions in the early steps of
      eubacterial 50 S ribosomal subunit assembly.
AB  - Although during the past decade research has shown the functional importance of
      disorder in proteins, many of the structural and dynamics properties of
      intrinsically unstructured proteins (IUPs) remain to be elucidated. This review
      is focused on the role of the extensions of the ribosomal proteins in the early
      steps of the assembly of the eubacterial 50 S subunit. The recent
      crystallographic structures of the ribosomal particles have revealed the picture
      of a complex assembly pathway that condenses the rRNA and the ribosomal proteins
      into active ribosomes. However, little is know about the molecular mechanisms of
      this process. It is thought that the long basic r-protein extensions that
      penetrate deeply into the subunit cores play a key role through disorder-order
      transitions and/or co-folding mechanisms. A current view is that such structural
      transitions may facilitate the proper rRNA folding. In this paper, the structures
      of the proteins L3, L4, L13, L20, L22 and L24 that have been experimentally found
      to be essential for the first steps of ribosome assembly have been compared. On
      the basis of their structural and dynamics properties, three categories of
      extensions have been identified. Each of them seems to play a distinct function.
      Among them, only the coil-helix transition that occurs in a phylogenetically
      conserved cluster of basic residues of the L20 extension appears to be strictly
      required for the large subunit assembly in eubacteria. The role of alpha helix
      coil transitions in 23 S RNA folding is discussed in the light of the calcium
      binding protein calmodulin that shares many structural and dynamics properties
      with L20.

PMID- 19399223
TI  - Model protocells from single-chain lipids.
AB  - Significant progress has been made in the construction of laboratory models of
      protocells. Most frequently the developed vesicle systems utilize single-chain
      lipids rather than the double-chain lipids typically found in biological
      membranes. Although single-chain lipids yield less robust vesicles, their dynamic
      characteristics are highly exploitable for protocellular functions. Herein the
      advantages of using single-chain lipids in the construction of protocells are
      discussed.

PMID- 19399224
TI  - Chaperonin structure: the large multi-subunit protein complex.
AB  - The multi sub-unit protein structure representing the chaperonins group is
      analyzed with respect to its hydrophobicity distribution. The proteins of this
      group assist protein folding supported by ATP. The specific axial symmetry GroEL
      structure (two rings of seven units stacked back to back - 524 aa each) and the
      GroES (single ring of seven units - 97 aa each) polypeptide chains are analyzed
      using the hydrophobicity distribution expressed as excess/deficiency all over the
      molecule to search for structure-to-function relationships. The empirically
      observed distribution of hydrophobic residues is confronted with the theoretical
      one representing the idealized hydrophobic core with hydrophilic residues
      exposure on the surface. The observed discrepancy between these two distributions
      seems to be aim-oriented, determining the structure-to-function relation. The
      hydrophobic force field structure generated by the chaperonin capsule is
      presented. Its possible influence on substrate folding is suggested.

PMID- 19399225
TI  - Grunwald-Winstein analysis: isopropyl chloroformate solvolysis revisited.
AB  - Specific rates of solvolysis at 25 degrees C for isopropyl chloroformate (1) in
      24 solvents of widely varying nucleophilicity and ionizing power, plus literature
      values for studies in water and formic acid, are reported. Previously published
      solvolytic rate constants at 40.0 degrees C are supplemented with two additional
      values in the highly ionizing fluoroalcohols. These rates are now are analyzed
      using the one and two-term Grunwald-Winstein Equations. In the more ionizing
      solvents including ten fluoroalcohols negligible sensitivities towards changes in
      solvent nucleophilicity (l) and very low sensitivities towards changes in solvent
      ionizing power (m) values are obtained, evocative to those previously observed
      for 1-adamantyl and 2-adamantyl chloroformates 2 and 3. These observations are
      rationalized in terms of a dominant solvolysis-decomposition with loss of the
      CO(2) molecule. In nine of the more nucleophilic pure alchohols and aqueous
      solutions an association-dissociation mechanism is believed to be operative.
      Deficiencies in the acid production indicate 2-33% isopropyl chloride formation,
      with the higher values in less nucleophilic solvents.

PMID- 19399226
TI  - Hypoglycemic effects of crude polysaccharide from Purslane.
AB  - The effects of crude polysaccharide from Purslane (CPP) on body weight (bw),
      blood glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL
      c), triglyceride (TG) and serum insulin levels were studied in diabetes mellitus
      mice. CPP treatment (200, 400 mg/kg bw) for 28 days resulted in a significant
      decrease in the concentrations of fasting blood glucose (FBG), TC and TG.
      Furthermore, CPP significantly increased the concentration of HDL-c, body weight
      and serum insulin level in the mice. In addition, according to acute toxicity
      studies and single cell gel electrophoresis analysis, CPP did not produce any
      physical or behavioral signs of toxicity. More significantly, our data
      demonstrated CPP exhibited the best effects at the dose of 400 mg/kg bw. The
      above results suggest that CPP can control blood glucose and modulate the
      metabolism of glucose and blood lipids in diabetes mellitus mice, so we conclude
      that CPP should be evaluated as a candidate for future studies on diabetes
      mellitus.

PMID- 19399227
TI  - Insights from coarse-grained Go models for protein folding and dynamics.
AB  - Exploring the landscape of large scale conformational changes such as protein
      folding at atomistic detail poses a considerable computational challenge. Coarse
      grained representations of the peptide chain have therefore been developed and
      over the last decade have proved extremely valuable. These include topology-based
      Go models, which constitute a smooth and funnel-like approximation to the folding
      landscape. We review the many variations of the Go model that have been employed
      to yield insight into folding mechanisms. Their success has been interpreted as a
      consequence of the dominant role of the native topology in folding. The role of
      local contact density in determining protein dynamics is also discussed and is
      used to explain the ability of Go-like models to capture sequence effects in
      folding and elucidate conformational transitions.

PMID- 19399228
TI  - Multiple, but concerted cellular activities of the human protein Hap46/BAG-1M and
      isoforms.
AB  - The closely related human and murine proteins Hap46/BAG-1M and BAG-1,
      respectively, were discovered more than a decade ago by molecular cloning
      techniques. These and the larger isoform Hap50/BAG-1L, as well as shorter
      isoforms, have the ability to interact with a seemingly unlimited array of
      proteins of completely unrelated structures. This problem was partially resolved
      when it was realized that molecular chaperones of the hsp70 heat shock protein
      family are major primary association partners, binding being mediated by the
      carboxy terminal BAG-domain and the ATP-binding domain of hsp70 chaperones. The
      latter, in turn, can associate with an almost unlimited variety of proteins
      through their substrate-binding domains, so that ternary complexes may result.
      The protein folding activity of hsp70 chaperones is affected by interactions with
      Hap46/BAG-1M or isoforms. However, there also exist several proteins which bind
      to Hap46/BAG-1M and isoforms independent of hsp70 mediation. Moreover, Hap46/BAG
      1M and Hap50/BAG-1L, but not the shorter isoforms, can bind to DNA in a sequence
      independent manner by making use of positively charged regions close to their
      amino terminal ends. This is the molecular basis for their effects on
      transcription which are of major physiological relevance, as discussed here in
      terms of a model. The related proteins Hap50/BAG-1L and Hap46/BAG-1M may thus
      serve as molecular links between such diverse bioactivities as regulation of gene
      expression and protein quality control. These activities are coordinated and
      synergize in helping cells to cope with conditions of external stress. Moreover,
      they recently became markers for the aggressiveness of several cancer types.

PMID- 19399229
TI  - Corrrelation of the specific rates of solvolysis of ethyl fluoroformate using the
      extended Grunwald-Winstein equation.
AB  - The specific rates of solvolysis of ethyl fluoroformate have been measured at
      24.2 degrees C in 21 pure and binary solvents. These give a satisfactory
      correlation over the full range of solvents when the extended Grunwald-Winstein
      equation is applied. The sensitivities to changes in the N(T) solvent
      nucleophilicity scale and the Y(Cl) solvent ionizing power scale, and the
      k(F)/k(Cl) values are very similar to those for solvolyses of n-octyl
      fluoroformate, consistent with the addition step of an addition-elimination
      pathway being rate-determining. For methanolysis, a solvent deuterium isotope
      effect of 3.10 is compatible with the incorporation of general-base catalysis
      into the substitution process. For five representative solvents, studies were
      made at several temperatures and activation parameters determined. The results
      are also compared with those reported earlier for ethyl chloroformate and
      mechanistic conclusions are drawn.

PMID- 19399230
TI  - The contribution of the elastic reaction is severely underestimated in studies on
      myofibril contraction.
AB  - We have considered the Huxley-Simmons manoeuvre. On the assumption that the quick
      release is an elastic process and on the basis of the isometric tension and of
      the stiffness of the muscle fibre we calculated that the spontaneous release of
      the fibre requires approximately 43 micros, which is much faster than the
      observed release, approximately 180 micros. We concluded that the observed quick
      release is a guided process. After proper selection of the mass and of the
      stiffness of the system we mimicked the early recovery and noticed that most of
      the energy required to accomplish the early recovery is supplied by the kinetic
      energy accumulated during the course of the quick release. We computed that the
      frequency of the working strokes in the half sarcomere was between 4x10(6) and
      40x10(6) s(-1). This is not to say that the ATPase rate constants are
      accumulative but only that the overall frequency of the working strokes in the
      half saromere is many orders of magnitude faster than the average ATPase rate
      constant. With this frequency no part of the Huxley-Simmons manoeuvre, quick
      release included, escapes the control of the working stroke. This means also that
      there is no reason to take the early recovery as an indication of the length of
      the working stroke.

PMID- 19399231
TI  - Improvement of morphine-mediated analgesia by inhibition of beta-arrestin2
      expression in mice periaqueductal gray matter.
AB  - Morphine is a well-known mu-opioid receptor (MOR) agonist and an efficient
      analgesic, but its long-term use inevitably leads to drug addiction and
      tolerance. Here, we show that specific inhibition of beta-arrestin2 with its
      siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG)
      significantly improved both acute and chronic morphine analgesia and delayed the
      tolerance in the hotplate test. The specific effect of beta-arrestin2 was proven
      by overexpression or knockdown of its homology beta-arrestin1 in PAG, which
      showed no significant effects on morphine analgesia. These findings suggest that
      specific siRNA targeting beta-arrestin2 may constitute a new approach to morphine
      therapy and other MOR agonist-mediated analgesia and tolerance.

PMID- 19399232
TI  - Kinetics of chromium(III) transport through a liquid membrane containing DNNSA as
      a carrier.
AB  - Kinetics of Cr(III) ions transport through a bulk liquid membrane containing
      dinonylnaphthalenesulfonic acid (DNNSA) as a carrier, flowing over aqueous
      phases, has been examined. Special attention has been paid to the effect of the
      membrane's velocity flow on the chromium concentration decrease in a feed phase.
      For the description of relationships of chromium(III) concentration in particular
      phases with the time, a model based on the assumption of consecutive first-order
      reactions was proposed. Satisfactory compatibility of experiments and model
      results have been obtained both for the membrane flow velocities below 0.0034
      m.s(-1) when the interfaces begin to fluctuate slightly and for low initial
      Cr(III) concentration in the feed phase.

PMID- 19399233
TI  - Molecular pathology of human prion diseases.
AB  - Prion diseases are fatal neurodegenerative conditions in humans and animals. In
      this review, we summarize the molecular background of phenotypic variability,
      relation of prion protein (PrP) to other proteins associated with
      neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP
      exists in different forms that may be present in both diseased and non-diseased
      brain, however, abundant disease-associated PrP together with tissue pathology
      characterizes prion diseases and associates with transmissibility. Prion diseases
      have different etiological background with distinct pathogenesis and phenotype.
      Mutations of the prion protein gene are associated with genetic forms. The codon
      129 polymorphism in combination with the Western blot pattern of PrP after
      proteinase K digestion serves as a basis for molecular subtyping of sporadic
      Creutzfeldt-Jakob disease. Tissue damage may result from several parallel,
      interacting or subsequent pathways that involve cellular systems associated with
      synapses, protein processing, oxidative stress, autophagy, and apoptosis.

PMID- 19399235
TI  - Probing the nanosecond dynamics of a designed three-stranded beta-sheet with a
      massively parallel molecular dynamics simulation.
AB  - Recently a temperature-jump FTIR study of a designed three-stranded sheet showing
      a fast relaxation time of approximately 140 +/- 20 ns was published. We performed
      massively parallel molecular dynamics simulations in explicit solvent to probe
      the structural events involved in this relaxation. While our simulations produce
      similar relaxation rates, the structural ensemble is broad. We observe the
      formation of turn structure, but only very weak interaction in the strand
      regions, which is consistent with the lack of strong backbone-backbone NOEs in
      previous structural NMR studies. These results suggest that either (D)P(D)P-II
      folds at time scales longer than 240 ns, or that (D)P(D)P-II is not a well
      defined three-stranded beta-sheet. This work also provides an opportunity to
      compare the performance of several popular forcefield models against one another.

PMID- 19399234
TI  - Neuropathology and therapeutic intervention in spinal and bulbar muscular
      atrophy.
AB  - Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease
      caused by the expansion of a polyglutamine tract in the androgen receptor (AR).
      The histopathological finding in SBMA is loss of lower motor neurons in the
      anterior horn of the spinal cord as well as in the brainstem motor nuclei. Animal
      studies have revealed that the pathogenesis of SBMA depends on the level of serum
      testosterone, and that androgen deprivation mitigates neurodegeneration through
      inhibition of nuclear accumulation of the pathogenic AR. Heat shock proteins,
      ubiquitin-proteasome system and transcriptional regulation are also potential
      targets of therapy development for SBMA.

PMID- 19399236
TI  - Quantitative prediction of solvation free energy in octanol of organic compounds.
AB  - The free energy of solvation, DeltaGS0, in octanol of organic compounds is
      quantitatively predicted from the molecular structure. The model, involving only
      three molecular descriptors, is obtained by multiple linear regression analysis
      from a data set of 147 compounds containing diverse organic functions, namely,
      halogenated and non-halogenated alkanes, alkenes, alkynes, aromatics, alcohols,
      aldehydes, ketones, amines, ethers and esters; covering a DeltaGS0 range from
      about -50 to 0 kJ.mol(-1). The model predicts the free energy of solvation with a
      squared correlation coefficient of 0.93 and a standard deviation, 2.4 kJ.mol(-1),
      just marginally larger than the generally accepted value of experimental
      uncertainty. The involved molecular descriptors have definite physical meaning
      corresponding to the different intermolecular interactions occurring in the bulk
      liquid phase. The model is validated with an external set of 36 compounds not
      included in the training set.

PMID- 19399238
TI  - Importance of translational entropy of water in biological self-assembly
      processes like protein folding.
AB  - We briefly review our studies on the folding/unfolding mechanisms of proteins. In
      biological self-assembly processes such as protein folding, the number of
      accessible translational configurations of water in the system increases greatly,
      leading to a large gain in the water entropy. The usual view looking at only the
      water in the close vicinity of the protein surface is capable of elucidating
      neither the large entropic gain upon apoplastocyanin folding, which has recently
      been found in a novel experimental study, nor the pressure and cold denaturation.
      With the emphasis on the translational entropy of water, we are presently
      constructing a reliable method for predicting the native structure of a protein
      from its amino-acid sequence.

PMID- 19399237
TI  - Molecular pathology of neuro-AIDS (CNS-HIV).
AB  - The cognitive deficits in patients with HIV profoundly affect the quality of life
      of people living with this disease and have often been linked to the neuro
      inflammatory condition known as HIV encephalitis (HIVE). With the advent of more
      effective anti-retroviral therapies, HIVE has shifted from a sub-acute to a
      chronic condition. The neurodegenerative process in patients with HIVE is
      characterized by synaptic and dendritic damage to pyramidal neurons, loss of
      calbindin-immunoreactive interneurons and myelin loss. The mechanisms leading to
      neurodegeneration in HIVE might involve a variety of pathways, and several lines
      of investigation have found that interference with signaling factors mediating
      neuroprotection might play an important role. These signaling pathways include,
      among others, the GSK3beta, CDK5, ERK, Pyk2, p38 and JNK cascades. Of these,
      GSK3beta has been a primary focus of many previous studies showing that in
      infected patients, HIV proteins and neurotoxins secreted by immune-activated
      cells in the brain abnormally activate this pathway, which is otherwise regulated
      by growth factors such as FGF. Interestingly, modulation of the GSK3beta
      signaling pathway by FGF1 or GSK3beta inhibitors (lithium, valproic acid) is
      protective against HIV neurotoxicity, and several pilot clinical trials have
      demonstrated cognitive improvements in HIV patients treated with GSK3beta
      inhibitors. In addition to the GSK3beta pathway, the CDK5 pathway has recently
      been implicated as a mediator of neurotoxicity in HIV, and HIV proteins might
      activate this pathway and subsequently disrupt the diverse processes that CDK5
      regulates, including synapse formation and plasticity and neurogenesis. Taken
      together, the GSK3beta and CDK5 signaling pathways are important regulators of
      neurotoxicity in HIV, and modulation of these factors might have therapeutic
      potential in the treatment of patients suffering from HIVE. In this context, the
      subsequent sections will focus on reviewing the involvement of the GSK3beta and
      CDK5 pathways in neurodegeneration in HIV.

PMID- 19399239
TI  - Dietary protection against free radicals: a case for multiple testing to
      establish structure-activity relationships for antioxidant potential of
      anthocyanic plant species.
AB  - DNA damage by reactive species is associated with susceptibility to chronic human
      degenerative disorders. Anthocyanins are naturally occurring antioxidants, that
      may prevent or reverse such damage. There is considerable interest in anthocyanic
      food plants as good dietary sources, with the potential for reducing
      susceptibility to chronic disease. While structure-activity relationships have
      provided guidelines on molecular structure in relation to free hydroxyl-radical
      scavenging, this may not cover the situation in food plants where the
      anthocyanins are part of a complex mixture, and may be part of complex
      structures, including anthocyanic vacuolar inclusions (AVIs). Additionally, new
      analytical methods have revealed new structures in previously-studied materials.
      We have compared the antioxidant activities of extracts from six anthocyanin-rich
      edible plants (red cabbage, red lettuce, blueberries, pansies, purple sweetpotato
      skin, purple sweetpotato flesh and Maori potato flesh) using three chemical
      assays (DPPH, TRAP and ORAC), and the in vitro Comet assay. Extracts from the
      flowering plant, lisianthus, were used for comparison. The extracts showed
      differential effects in the chemical assays, suggesting that closely related
      structures have different affinities to scavenge different reactive species.
      Integration of anthocyanins to an AVI led to more sustained radical scavenging
      activity as compared with the free anthocyanin. All but the red lettuce extract
      could reduce endogenous DNA damage in HT-29 colon cancer cells. However, while
      extracts from purple sweetpotato skin and flesh, Maori potato and pansies,
      protected cells against subsequent challenge by hydrogen peroxide at 0 degrees C,
      red cabbage extracts were pro-oxidant, while other extracts had no effect. When
      the peroxide challenge was at 37 degrees C, all of the extracts appeared pro
      oxidant. Maori potato extract, consistently the weakest antioxidant in all the
      chemical assays, was more effective in the Comet assays. These results highlight
      the dangers of generalising to potential health benefits, based solely on
      identification of high anthocyanic content in plants, results of a single
      antioxidant assay and traditional approaches to structure activity relationships.
      Subsequent studies might usefully consider complex mixtures and a battery of
      assays.

PMID- 19399240
TI  - Calcium ions regulate K+ uptake into brain mitochondria: the evidence for a novel
      potassium channel.
AB  - The mitochondrial response to changes of cytosolic calcium concentration has a
      strong impact on neuronal cell metabolism and viability. We observed that Ca(2+)
      additions to isolated rat brain mitochondria induced in potassium ion containing
      media a mitochondrial membrane potential depolarization and an accompanying
      increase of mitochondrial respiration. These Ca(2+) effects can be blocked by
      iberiotoxin and charybdotoxin, well known inhibitors of large conductance
      potassium channel (BK(Ca) channel). Furthermore, NS1619 - a BK(Ca) channel opener
      - induced potassium ion-specific effects on brain mitochondria similar to those
      induced by Ca(2+). These findings suggest the presence of a calcium-activated,
      large conductance potassium channel (sensitive to charybdotoxin and NS1619),
      which was confirmed by reconstitution of the mitochondrial inner membrane into
      planar lipid bilayers. The conductance of the reconstituted channel was 265 pS
      under gradient (50/450 mM KCl) conditions. Its reversal potential was equal to 50
      mV, which proved that the examined channel was cation-selective. We also observed
      immunoreactivity of anti-beta(4) subunit (of the BK(Ca) channel) antibodies with
      ~26 kDa proteins of rat brain mitochondria. Immunohistochemical analysis
      confirmed the predominant occurrence of beta(4) subunit in neuronal mitochondria.
      We hypothesize that the mitochondrial BK(Ca) channel represents a calcium sensor,
      which can contribute to neuronal signal transduction and survival.

PMID- 19399241
TI  - Folding of Trp-cage mini protein using temperature and biasing potential replica
      exchange molecular dynamics simulations.
AB  - The folding process of the 20 residue Trp-cage mini-protein was investigated
      using standard temperature replica exchange molecular dynamics (T-RexMD)
      simulation and a biasing potential RexMD (BP-RexMD) method. In contrast to
      several conventional molecular dynamics simulations, both RexMD methods sampled
      conformations close to the native structure after 10-20 ns simulation time as the
      dominant conformational states. In contrast, to T-RexMD involving 16 replicas the
      BP-RexMD method achieved very similar sampling results with only five replicas.
      The result indicates that the BP-RexMD method is well suited to study folding
      processes of proteins at a significantly smaller computational cost, compared to
      T-RexMD. Both RexMD methods sampled not only similar final states but also agreed
      on the sampling of intermediate conformations during Trp-cage folding. The
      analysis of the sampled potential energy contributions indicated that Trp-cage
      folding is favored by both van der Waals and to a lesser degree electrostatic
      contributions. Folding does not introduce any significant sterical strain as
      reflected by similar energy distributions of bonded energy terms (bond length,
      bond angle and dihedral angle) of folded and unfolded Trp-cage structures.

PMID- 19399242
TI  - Changes in metallothionein level in rat hepatic tissue after administration of
      natural mouldy wheat.
AB  - Mycotoxins are secondary metabolites produced by microfungi that are capable of
      causing disease and death in humans and other animals. This work was aimed at
      investigation of influence of mouldy wheat contaminated by pathogenic fungi
      producing mycotoxins on metallothionein levels in hepatic tissue of rats. The
      rats were administrating feed mixtures with different contents of vitamins or
      naturally mouldy wheat for 28 days. It was found that the wheat contained
      deoxynivalenol (80 +/- 5 microg per kg of mouldy wheat), zearalenone (56 +/- 3
      microg/kg), T2-toxin (20 +/- 2 microg/kg) and aflatoxins as a sum of B1, B2, G1
      and G2 (3.9 +/- 0.2 microg/kg). Rats were fed diets containing 0, 33, 66 and 100%
      naturally moulded wheat. Control group 0, 33, 66 and 100% contained vitamins
      according to Nutrient Requirements of Rats (NRC). Other four groups (control
      group with vitamins, vit33, vit66 and vit100%) were fed on the same levels of
      mouldy wheat, also vitamins at levels 100% higher than the previous mixtures. We
      determined weight, feed conversion and performed dissection to observe
      pathological processes. Changes between control group and experimental groups
      exposed to influence of mouldy wheat and experimental groups supplemented by
      higher concentration of vitamins and mouldy wheat were not observed. Livers were
      sampled and did not demonstrate significant changes in morphology compared to
      control either. In the following experiments the levels of metallothionein as a
      marker of oxidative stress was determined. We observed a quite surprising trend
      in metallothionein levels in animals supplemented with increased concentration of
      vitamins. Its level enhanced with increasing content of mouldy wheat. It was
      possible to determine a statistically significant decline (p<0.05) between
      control group and groups of animals fed with 33, 66 and 100% mouldy wheat. It is
      likely that some mycotoxins presented in mouldy wheat are able to block the
      mechanism of metallothionein synthesis.

PMID- 19399244
TI  - Quantum-SAR extension of the spectral-SAR algorithm: application to polyphenolic
      anticancer bioactivity.
AB  - Aiming to assess the role of individual molecular structures in the molecular
      mechanism of ligand-receptor interaction correlation analysis, the recent
      Spectral-SAR approach is employed to introduce the Quantum-SAR (QuaSAR) "wave"
      and "conversion factor" in terms of difference between inter-endpoint inter
      molecular activities for a given set of compounds; this may account for inter
      conversion (metabolization) of molecular (concentration) effects while indicating
      the structural (quantum) based influential/detrimental role on bio-/eco- effect
      in a causal manner rather than by simple inspection of measured values; the
      introduced QuaSAR method is then illustrated for a study of the activity of a
      series of flavonoids on breast cancer resistance protein.

PMID- 19399243
TI  - Philosophical basis and some historical aspects of systems biology: from Hegel to
      Noble - applications for bioenergetic research.
AB  - We live in times of paradigmatic changes for the biological sciences.
      Reductionism, that for the last six decades has been the philosophical basis of
      biochemistry and molecular biology, is being displaced by Systems Biology, which
      favors the study of integrated systems. Historically, Systems Biology - defined
      as the higher level analysis of complex biological systems - was pioneered by
      Claude Bernard in physiology, Norbert Wiener with the development of cybernetics,
      and Erwin Schrodinger in his thermodynamic approach to the living. Systems
      Biology applies methods inspired by cybernetics, network analysis, and non
      equilibrium dynamics of open systems. These developments follow very precisely
      the dialectical principles of development from thesis to antithesis to synthesis
      discovered by Hegel. Systems Biology opens new perspectives for studies of the
      integrated processes of energy metabolism in different cells. These integrated
      systems acquire new, system-level properties due to interaction of cellular
      components, such as metabolic compartmentation, channeling and functional
      coupling mechanisms, which are central for regulation of the energy fluxes. State
      of the art of these studies in the new area of Molecular System Bioenergetics is
      analyzed.

PMID- 19399245
TI  - Ultra low-dose radiation: stress responses and impacts using rice as a grass
      model.
AB  - We report molecular changes in leaves of rice plants (Oryza sativa L. - reference
      crop plant and grass model) exposed to ultra low-dose ionizing radiation, first
      using contaminated soil from the exclusion zone around Chernobyl reactor site.
      Results revealed induction of stress-related marker genes (Northern blot) and
      secondary metabolites (LC-MS/MS) in irradiated leaf segments over appropriate
      control. Second, employing the same in vitro model system, we replicated results
      of the first experiment using in-house fabricated sources of ultra low-dose gamma
      (gamma) rays and selected marker genes by RT-PCR. Results suggest the usefulness
      of the rice model in studying ultra low-dose radiation response/s.

PMID- 19399247
TI  - Dielectric properties of binary solvent mixtures of dimethyl sulfoxide with
      water.
AB  - In this paper, the dielectric properties of water-dimethylsulfoxide (DMSO)
      mixtures with different mole ratios have been investigated in the range of 1 GHz
      to 40 GHz at 298 K by using a molecular dynamics (MD) simulation. Only one
      dielectric loss peak was observed in the frequency range and the relaxation in
      these mixtures can be described by a single relaxation time of the Davidson-Cole.
      It was observed that within experimental error the dielectric relaxation can be
      described by the Debye-like model (beta approximately 1, S.M. Puranik, et al. J.
      Chem. Soc. Faraday Trans.1992, 88, 433 - 435). In general, the results are very
      consistent with the experimental measurements.

PMID- 19399248
TI  - Explaining ionic liquid water solubility in terms of cation and anion
      hydrophobicity.
AB  - The water solubility of salts is ordinarily dictated by lattice energy and ion
      solvation. However, in the case of low melting salts also known as ionic liquids,
      lattice energy is immaterial and differences in hydrophobicity largely account
      for differences in their water solubility. In this contribution, the activity
      coefficients of ionic liquids in water are split into cation and anion
      contributions by regression against cation hydrophobicity parameters that are
      experimentally determined by reversed phase liquid chromatography. In this way,
      anion hydrophobicity parameters are derived, as well as an equation to estimate
      water solubilities for cation-anion combinations for which the water solubility
      has not been measured. Thus, a new pathway to the quantification of aqueous ion
      solvation is shown, making use of the relative weakness of interactions between
      ionic liquid ions as compared to their hydrophobicities.

PMID- 19399249
TI  - Origin of homochirality in biosystems.
AB  - Experimental data for a series of central and simple molecules in biosystems show
      that some amino acids and a simple sugar molecule have a chiral discrimination in
      favor of homochirality. Models for segregation of racemic mixtures of chiral
      amphiphiles and lipophiles in aqueous solutions show that the amphiphiles with an
      active isomerization kinetics can perform a spontaneous break of symmetry during
      the segregation and self-assembly to homochiral matter. Based on this observation
      it is argued that biomolecules with a sufficiently strong chiral discrimination
      could be the origin of homochirality in biological systems.

PMID- 19399246
TI  - Physiological and pathological role of alpha-synuclein in Parkinson's disease
      through iron mediated oxidative stress; the role of a putative iron-responsive
      element.
AB  - Parkinson's disease (PD) is the second most common progressive neurodegenerative
      disorder after Alzheimer's disease (AD) and represents a large health burden to
      society. Genetic and oxidative risk factors have been proposed as possible
      causes, but their relative contribution remains unclear. Dysfunction of alpha
      synuclein (alpha-syn) has been associated with PD due to its increased presence,
      together with iron, in Lewy bodies. Brain oxidative damage caused by iron may be
      partly mediated by alpha-syn oligomerization during PD pathology. Also, alpha-syn
      gene dosage can cause familial PD and inhibition of its gene expression by
      blocking translation via a newly identified Iron Responsive Element-like RNA
      sequence in its 5'-untranslated region may provide a new PD drug target.

PMID- 19399250
TI  - In vitro models in biocompatibility assessment for biomedical-grade chitosan
      derivatives in wound management.
AB  - One of the ultimate goals of wound healing research is to find effective healing
      techniques that utilize the regeneration of similar tissues. This involves the
      modification of various wound dressing biomaterials for proper wound management.
      The biopolymer chitosan (beta-1,4-D-glucosamine) has natural biocompatibility and
      biodegradability that render it suitable for wound management. By definition, a
      biocompatible biomaterial does not have toxic or injurious effects on biological
      systems. Chemical and physical modifications of chitosan influence its
      biocompatibility and biodegradability to an uncertain degree. Hence, the modified
      biomedical-grade of chitosan derivatives should be pre-examined in vitro in order
      to produce high-quality, biocompatible dressings. In vitro toxicity examinations
      are more favorable than those performed in vivo, as the results are more
      reproducible and predictive. In this paper, basic in vitro tools were used to
      evaluate cellular and molecular responses with regard to the biocompatibility of
      biomedical-grade chitosan. Three paramount experimental parameters of
      biocompatibility in vitro namely cytocompatibility, genotoxicity and skin pro
      inflammatory cytokine expression, were generally reviewed for biomedical-grade
      chitosan as wound dressing.

PMID- 19399252
TI  - Participation of low molecular weight electron carriers in oxidative protein
      folding.
AB  - Oxidative protein folding is mediated by a proteinaceous electron relay system,
      in which the concerted action of protein disulfide isomerase and Ero1 delivers
      the electrons from thiol groups to the final acceptor. Oxygen appears to be the
      final oxidant in aerobic living organisms, although the existence of alternative
      electron acceptors, e.g. fumarate or nitrate, cannot be excluded. Whilst the
      protein components of the system are well-known, less attention has been turned
      to the role of low molecular weight electron carriers in the process. The
      function of ascorbate, tocopherol and vitamin K has been raised recently. In
      vitro and in vivo evidence suggests that these redox-active compounds can
      contribute to the functioning of oxidative folding. This review focuses on the
      participation of small molecular weight redox compounds in oxidative protein
      folding.

PMID- 19399251
TI  - Mechanism of suppression of protein aggregation by alpha-crystallin.
AB  - This review summarizes experimental data illuminating the mechanism of
      suppression of heat-induced protein aggregation by alpha-crystallin, one of the
      small heat shock proteins. The dynamic light scattering data show that the
      initial stage of thermal aggregation of proteins is the formation of the initial
      aggregates involving hundreds of molecules of the denatured protein. Further
      sticking of the starting aggregates proceeds in a regime of diffusion-limited
      cluster-cluster aggregation. The protective effect of alpha-crystallin is due to
      transition of the aggregation process to the regime of reaction-limited cluster
      cluster aggregation, wherein the sticking probability for the colliding particles
      becomes lower than unity.

PMID- 19399253
TI  - Protein dynamics: from molecules, to interactions, to biology.
AB  - Proteins have a remarkably rich diversity of dynamical behaviors, and the
      articles in this issue of the International Journal of Molecular Sciences are a
      testament to that fact. From the picosecond motions of single sidechains probed
      by NMR or fluorescence spectroscopy, to aggregation processes at interfaces that
      take months, all time scales play a role. Proteins are functional molecules, so
      by their nature they always interact with their environment. This environment
      includes water, other biomolecules, or larger cellular structures. In a sense, it
      also includes the protein molecule itself: proteins are large enough to fold and
      interact with themselves. These interactions have been honed by evolution to
      produce behaviors completely different from those of random polymers.

PMID- 19399254
TI  - Slow unfolding of monomeric proteins from hyperthermophiles with reversible
      unfolding.
AB  - Based on the differences in their optimal growth temperatures microorganisms can
      be classified into psychrophiles, mesophiles, thermophiles, and
      hyperthermophiles. Proteins from hyperthermophiles generally exhibit greater
      stability than those from other organisms. In this review, we collect data about
      the stability and folding of monomeric proteins from hyperthermophilies with
      reversible unfolding, from the equilibrium and kinetic aspects. The results
      indicate that slow unfolding is a general strategy by which proteins from
      hyperthermophiles adapt to higher temperatures. Hydrophobic interaction is one of
      the factors in the molecular mechanism of the slow unfolding of proteins from
      hyperthermophiles.

PMID- 19399256
TI  - AFM and multiple transmission-reflection infrared spectroscopy (MTR-IR) studies
      on formation of air-stable supported lipid bilayers.
AB  - Supported lipid bilayers (SLBs) were prepared by deposition of unilamellar
      vesicles on a silicon substrate. Atomic force microscopy (AFM) and a new Multiple
      Transmission-Reflection Infrared Spectroscopy (MTR-IR) developed by us were used
      to trace the dynamic formation of lipid bilayers on the silicon surfaces. The
      evolution from deformation of vesicles to formation of bilayers can be
      distinguished clearly by AFM imaging. MTR-IR provided high quality infrared
      spectra of ultrathin lipid bilayers with high sensitivity and high signal to
      noise ratio (SNR). The structural and orientational changes during vesicle's
      fusion were monitored with MTR-IR. MTR-IR shows superiority over other infrared
      approaches for ultrathin films on standard silicon wafers in view of its economy
      and high sensitivity. Both MTR-IR and AFM results were consistent with each other
      and they provided more information for understanding the self-assembling
      procedure of SLBs.

PMID- 19399257
TI  - DNA microarray-based gene expression profiling in porcine keratocytes and corneal
      endothelial cells and comparative analysis associated with xeno-related
      rejection.
AB  - Porcine to rat corneal xenotransplantation resulted in severe inflammation and
      rejection of the corneal stroma, whereas an allograft showed mainly endothelial
      cell-associated rejection. We, therefore, investigated and compared the gene
      expression between porcine keratocytes and corneal endothelial cells. RNA was
      isolated from primary cultured porcine or human keratocytes and porcine corneal
      endothelial cells. Gene expression was comparatively analyzed after normalization
      with microarray method using Platinum pig 13 K oligo chip (GenoCheck Co., Ltd.,
      Ansan, Korea). Real-time polymerase chain reaction (PCR) was performed for C1R,
      CCL2, CXCL6, and HLA-A in porcine keratocytes and corneal endothelial cells. As a
      result, upregulated expression more than 2 folds was observed in 1,162 genes of
      porcine keratocytes versus porcine endothelial cells. Among the immune-regulatory
      genes, SEMA3C, CCL2, CXCL6, F3, HLA-A, CD97, IFI30, C1R, and G1P3 were highly
      expressed in porcine keratocytes, compared to porcine corneal endothelial cells
      or human keratocytes. When measured by real-time PCR, the expression of C1R,
      CCL2, and HLA-A was higher in porcine keratocytes compared to that in porcine
      corneal endothelial cells. In conclusion, the increased expression of C1R, CCL2,
      and HLA-A genes in porcine keratocytes might be responsible for the stromal
      rejection observed in a porcine to rat corneal xenotransplantation.

PMID- 19399255
TI  - Molecular pathogenesis of Alzheimer's disease: reductionist versus expansionist
      approaches.
AB  - Alzheimer's disease (AD) is characterized clinically by dementia and
      pathologically by two hallmark lesions, senile plaques and neurofibrillary
      tangles. About a quarter century ago these hallmark lesions were purified and
      their protein constituents identified, precipitating an avalanche of molecular
      studies as well as substantial optimism about successful therapeutic
      intervention. In 2009, we now have copious knowledge on the biochemical cascades
      that produce these proteins, the different modifications and forms in which these
      proteins exist, and the ability to selectively target these proteins for
      therapeutic intervention on an experimental basis. At the same time, there has
      been no discernible alteration in the natural course of AD in humans. While it
      may be that the complexity of AD will exceed our capacity to make significant
      treatment progress for decades or more, a paradigm shift from the reductionism
      that defines amyloid-beta and tau hypotheses, to one that more accurately
      reflects the meaning of neuropathological changes, may be warranted. We and
      others have demonstrated that AD pathology is a manifestation of cellular
      adaptation, specifically as a defense against oxidative injury. As such, AD
      pathology is therefore a host response rather than a manifestation of cytotoxic
      protein injury, and is unlikely to be a fruitful target for therapeutic
      intervention. An "expansionist" view of the disease, we believe, with oxidative
      stress as a pleiotropic and upstream process, more aptly describes the
      relationship between various and numerous molecular alterations and clinical
      disease.

PMID- 19399258
TI  - The prevalence and clinical characteristics of reflux esophagitis in koreans and
      its possible relation to metabolic syndrome.
AB  - The prevalence of reflux esophagitis is increasing in Korea. To estimate the
      prevalence and clinical characteristics of reflux esophagitis in healthy
      subjects, we retrospectively examined the medical records of healthy subjects
      undergoing a routine check-up from October 2004 to September 2005. A total of
      6,082 (3,590 men, mean age 44+/-10 yr) subjects were enrolled in this study. The
      prevalence of reflux esophagitis in healthy subjects was 10.5%. According to the
      univariate analysis, male sex (odds ratio [OR] 3.49, 95% confidence interval [CI]
      2.84-4.30), smoking history (OR 1.91, 95% CI 1.60-2.28), body mass index (BMI)
      >30 kg/m(2) (OR 2.13, 95% CI 1.37-3.33), total cholesterol >250 mg/dL (OR 1.50,
      95% CI 1.05-2.14), low-density lipoprotein (LDL) cholesterol >/=160 mg/dL (OR
      1.52, 95% CI 1.08-2.14), triglyceride >/=150 mg/dL (OR 1.92, 95% CI 1.61-2.30),
      high blood pressure (BP) (OR 1.46, 95% CI 1.20-1.76), and fasting glucose >/=110
      mg/dL (OR 1.45, 95% CI 1.13-1.86) were significantly associated with reflux
      esophagitis (all p<0.05). However, age, alcohol drinking and Helicobacter pylori
      infection were not associated with reflux esophagitis. In conclusion, significant
      relationships of reflux esophagitis with obesity, low high-density lipoprotein
      (HDL) cholesterol, high triglyceride, high BP, and elevated fasting glucose
      suggested that reflux esophagitis might represent the disease spectrum of the
      metabolic syndrome.

PMID- 19399259
TI  - Does the mitral annulus shrink or enlarge during systole? A real-time 3D
      echocardiography study.
AB  - This study was conducted to explore the geometrical changes of the mitral annulus
      during systole. The 3D shape of the mitral annulus was reconstructed in 13 normal
      subjects who had normal structure of the mitral apparatus using real-time 3D
      echocardiography (RT3DE) and 3D computer software. The two orthogonal (antero
      posterior and commissure-commissure) dimensions, the areas (2D projected and 3D
      surface) and the non-planarity of the mitral annulus were estimated during early,
      mid and late systole. We demonstrated that the MA had a "saddle shape" appearance
      and it consistently enlarged mainly in the antero-posterior direction from early
      to late systole with lessening of its non-planarity, as was determined by 3D
      reconstruction using RT3DE and 3D computer software.

PMID- 19399260
TI  - The impact of smoking on clinical and therapeutic effects in asthmatics.
AB  - Smoking is associated with poor symptom control and impaired therapeutic
      responses in asthma. A total of 843 patients with asthma were recruited. The
      patients received treatment for 1 yr according to the severity of their asthma.
      We compared the forced expiratory volume in 1 sec (FEV1), the ratio of FEV1 to
      forced vital capaity (FVC), atopy, total IgE, emphysema on high-resolution
      computed tomography (HRCT), the number of near-fatal asthma attacks, and
      physiological fixed airway obstruction between the smoking and nonsmoking groups.
      The study population consisted of 159 (18.8%) current smokers, 157 (18.7%) ex
      smokers, and 525 (62.5%) nonsmokers. Although the prevalence of atopy was not
      different between the smoking and nonsmoking groups, the total IgE was higher
      among the smokers than the nonsmokers. Compared with the nonsmoking group, the
      smokers had a lower FEV1 % predicted and forced expiratory flow between 25 and
      75% of FVC. A greater prevalence of emphysema and a significantly higher number
      of asthmatic patients with fixed airway obstruction were detected in the smoking
      versus nonsmoking group. The 37.5% of asthmatic patients who were former or
      current smokers showed decreased pulmonary function and increased IgE, emphysema
      on HRCT, and fixed airway obstruction, indicating that smoking can modulate the
      clinical and therapeutic responses in asthma.

PMID- 19399261
TI  - Childhood predictors of deliberate self-harm behavior and suicide ideation in
      korean adolescents: a prospective population-based follow-up study.
AB  - The aim of this study was to investigate predictors of adolescence suicidality in
      a longitudinal study. Additionally, the prevalence of deliberate self-harm
      behavior and suicide ideation at age 7 and during middle school were examined.
      Initial assessment data was obtained from 1998 to 2000, and a follow-up
      assessment was performed in 2006 when the original subjects became middle school
      students. The addresses and names of 1,857 subjects were located from the
      original data; they were 910 boys and 947 girls. The subjects were evaluated with
      the Korean version of the Child Behavior Checklist (K-CBCL), which was
      administered by the parents of the children, and by various demographic and
      psychosocial factors. They were reassessed using self reports on the Korea Youth
      Self Report (K-YSR); in particular, replies to items related to self-harm
      behavior and suicide ideation were recorded. A logistic regression analysis
      showed that the factors of gender, economic status, the overall amount of
      behavior problems, the tendency to internalizing and externalizing problems,
      somatic problems, thought problems, delinquent behavior, and aggressive behavior
      were independent predictors of adolescent suicide ideation and self-harm
      behavior. The importance of total behavior problems suggested that adolescent
      difficulty is a consequence of an accumulation of various risk factors.
      Accordingly, clinicians must consider a range of internalizing and externalizing
      issues, especially overall adaptation, for suicide intervention.

PMID- 19399262
TI  - Clinical effects of calcium channel blocker and Angiotensin converting enzyme
      inhibitor on endothelial function and arterial stiffness in patients with angina
      pectoris.
AB  - To evaluate the effects of calcium channel blocker (CCB) and angiotensin
      converting enzyme inhibitor (ACEI) on endothelial function and arterial stiffness
      in stable angina pectoris (SAP), 87 patients with SAP (57.6+/-10.0 yr, 52 males)
      were divided into two groups; CCB group (group I: n=44, 57.9+/-9.7 yr, 23 males)
      vs. CCB plus ACEI group (group II: n=43, 57.2+/-10.5 yr, 29 males). Flow mediated
      vasodilation (FMD) of the brachial artery, pulse wave velocity (PWV), urinary
      albumin excretion (UAE), and high sensitivity C-reactive protein (hsCRP) were
      compared. FMD, PWV, UAE, and hsCRP were not different between the groups at
      baseline. After 6 months of treatment, FMD were significantly improved in group
      II (7.5+/-3.7 to 8.8+/-2.7%, p<0.001), but not in group I (7.9+/-2.7 to 8.2+/
      2.8%, p=0.535). Brachial-ankle PWV were significantly improved in both groups
      (1,621.3+/-279.4 to 1,512.1+/-225.0 cm/sec in group I, p<0.001, 1,586.8+/-278.5
      to 1,434.5+/-200.5 cm/sec in group II, p<0.001). However, heart-femoral PWV were
      significantly improved (1,025.7+/-145.1 to 946.2+/-112.2 cm/sec, p<0.001) and UAE
      were significantly decreased (20.19+/-29.92 to 13.03+/-16.42 mg/g Cr, p=0.019) in
      group II only. In conclusion, combination therapy with CCB and ACEI improves
      endothelial function, arterial stiffness, and UAE than CCB mono-therapy more
      effectively in patients with SAP.

PMID- 19399263
TI  - Modifications of T-scores by quantitative ultrasonography for the diagnosis of
      osteoporosis in koreans.
AB  - To identify a proper T-score threshold for the diagnosis of osteoporosis in
      Koreans using quantitative ultrasonography (QUS), normative data from 240 females
      and 238 males (ages 20-29 yr) were newly generated. Then, the osteoporosis
      prevalence estimate for men and women over 50 yr of age was analyzed using
      previous World Health Organization (WHO) methods and heel QUS. T-scores were
      calculated from the normative data. There were definite negative correlations
      between age and all of the QUS parameters, such as speed of sound (SOS),
      broadband ultrasound attenuation (BUA), and estimated heel bone mineral density
      (BMD) (p<0.0001). After applying the recently determined prevalence of incident
      vertebral fracture in Koreans over 50 yr of age (11.6% and 9.1%, female vs male,
      respectively) to the diagnosis of osteoporosis by T-scores from heel BMD as
      measured by QUS, it was revealed that applicable T-scores for women and men were 
      2.25 and -1.85, respectively. These data suggest that simply using a T-score of 
      2.5, the classical WHO threshold for osteoporosis, underestimates the true
      prevalence when using peripheral QUS. Further prospective study of the power of
      QUS in predicting the absolute risk of fracture is needed.

PMID- 19399264
TI  - Prevalence and its predictors of extrapulmonary involvement in patients with
      pulmonary tuberculosis.
AB  - Extrapulmonary organ involvement in human immunodefiaency virus (HIV)-infected
      patients with pulmonary tuberculosis (TB) is reported to be 26%, however, the
      clinical predictors of extrapulmonary involvement in pulmonary TB patients has
      not been reported yet. We tried to determine the clinical predictors of presence
      of extrapulmonary involvement in patients with pulmonary TB. Cross-sectional
      study was performed including all adult patients with culture-proven pulmonary TB
      diagnosed between January 1, 2004 and July 30, 2006, at a tertiary referral
      hospital in South Korea. The presence of extra-pulmonary TB involvement was
      diagnosed based on bacteriological, pathological, or clinical evidence. Among 320
      patients with a culture-proven pulmonary TB, 40 had extrapulmonary involvement.
      Patients with bilateral lung involvement were more likely to have extrapulmonary
      involvement, with an adjusted odds ratio (OR) of 4.21 (95% confidence interval
      [CI], 1.82-9.72), while patients older than 60 yr (adjusted OR, 0.27; 95% CI,
      0.08-0.89), patients with cavitary lesions (adjusted OR, 0.37; 95% CI, 0.16
      0.84), and with higher levels of serum albumin (adjusted OR, 0.45; 95% CI, 0.25
      0.78) had less frequent involvement. Clinicians should be aware of the
      possibility of extrapulmonary involvement in TB patients with bilateral lung
      involvement without cavity formation or lower levels of serum albumin.

PMID- 19399265
TI  - The efficacy of hepatic resection after neoadjuvant transarterial
      chemoembolization (TACE) and radiation therapy in hepatocellular carcinoma
      greater than 5 cm in size.
AB  - In cases of large hepatocellular carcinoma (HCC), neoadjuvant treatment such as
      transarterial chemoembolization (TACE) and radiation therapy can be performed.
      The aim of this study was to evaluate the outcome of these treatments prior to
      hepatic resection. Between January 1994 and May 2007, 16 patients with HCC
      greater than 5 cm in size were treated with TACE and radiation therapy prior to
      hepatic resection. The clinicopathologic factors were reviewed retrospectively.
      Of the 16 patients, there were 14 men and two women, and the median age was 52.5
      yr. TACE was performed three times in average, and the median radiation dosage
      was 45 Gy. The median diameter of tumor on specimen was 9.0 cm. The degree of
      tumor necrosis was more than 90% in 14 patients. The median survival time was
      13.3 months. Five patients had survived more than 2 yr and there were two
      patients who had survived more than 5 yr. Although the prognosis of large HCC
      treated with neoadjuvant therapy is not satisfactory, some showed long-term
      survival loger than 5 yr. Further research will be required to examine the
      survival and disease control effect in a prospective randomized study.

PMID- 19399266
TI  - Multi-institutional comparison of intensity modulated radiation therapy (IMRT)
      planning strategies and planning results for nasopharyngeal cancer.
AB  - The intensity-modulated radiation therapy (IMRT) planning strategies for
      nasopharyngeal cancer among Korean radiation oncology facilities were
      investigated. Five institutions with IMRT planning capacity using the same
      planning system were invited to participate in this study. The institutions were
      requested to produce the best plan possible for 2 cases that would deliver 70 Gy
      to the planning target volume of gross tumor (PTV1), 59.4 Gy to the PTV2, and
      51.5 Gy to the PTV3 in which elective irradiation was required. The advised
      fractionation number was 33. The planning parameters, resultant dose
      distributions, and biological indices were compared. We found 2-3-fold variations
      in the volume of treatment targets. Similar degree of variation was found in the
      delineation of normal tissue. The physician-related factors in IMRT planning had
      more influence on the plan quality. The inhomogeneity index of PTV dose ranged
      from 4 to 49% in Case 1, and from 5 to 46% in Case 2. Variation in tumor control
      probabilities for the primary lesion and involved LNs was less marked. Normal
      tissue complication probabilities for parotid glands and skin showed marked
      variation. Results from this study suggest that greater efforts in providing
      training and continuing education in terms of IMRT planning parameters usually
      set by physician are necessary for the successful implementation of IMRT.

PMID- 19399267
TI  - Type VII collagen gene mutations (c.8569G>T and c.4879G>A) result in the
      moderately severe phenotype of recessive dystrophic epidermolysis bullosa in a
      Korean patient.
AB  - Dystrophic epidermolysis bullosa (DEB) are caused by mutations in the COL7A1
      gene, which encodes type VII collagen. Even though more than 500 different COL7A1
      mutations have been identified in DEB, it still remains to be under-investigated.
      To investigate the mutation of COL7A1 in moderately severe phenotype of recessive
      DEB (RDEB) in a Korean patient, the mutation detection strategy was consisted of
      polymerase chain reaction (PCR) amplification of genomic DNA, followed by
      heteroduplex analysis, nucleotide sequencing of the PCR products demonstrating
      altered mobility. In this study, we found that one mutation (c.8569G>T) was
      detected within exon 116. The mutation of c.8569G>T in exon 116 changed the GAG
      (Glu) to TAG, eventually resulted in premature termination of type VII collagen
      polypeptide. Furthermore the mother did not have the mutation c.8569G>T in exon
      116. The other novel mutation (c.4879G>A) was detected within exon 51 of both
      patient and mother, thereby resulting in changing valine (Val) to isoleucine
      (Ile) in type VII collagen polypeptide. Taken together, in this study we
      identified compound heterozygosity for COL7A1 mutations (c.8569G>T and c.4879G>A)
      in moderately severe RDEB in a Korean patient. We hope that this data contribute
      to the expanding database on COL7A1 mutations in DEB.

PMID- 19399268
TI  - Cessation of gonadotropin-releasing hormone antagonist on triggering day: an
      alternative method for flexible multiple-dose protocol.
AB  - This study was performed to analyze retrospectively outcomes of stimulated in
      vitro fertilization (IVF) cycles where the gonadotropin-releasing hormone (GnRH)
      antagonist was omitted on ovulation triggering day. A total of 92 consecutive IVF
      cycles were included in 65 women who are undergoing ovarian stimulation with
      recombinant FSH. A GnRH antagonist, cetrorelix 0.25 mg/day, was started when
      leading follicle reached 14 mm in diameter until the day of hCG administration
      (Group A, 66 cycles) or until the day before hCG administration (Group B, 26
      cycles). The duration of ovarian stimulation, total dose of gonadotropins, serum
      estradiol levels on hCG administration day, and the number of oocytes retrieved
      were not significantly different between the two groups. The total dose of GnRH
      antagonist was significantly lower in Group B compared to Group A (2.7+/-0.8 vs.
      3.2+/-0.9 ampoules). There was no premature luteinization in the subjects. The
      proportion of mature oocytes (71.4% vs. 61.7%) and fertilization rate of mature
      (86.3+/-19.7% vs. 71.8+/-31.7%) was significantly higher in Group B. There were
      no significant differences in embryo quality and clinical pregnancy rates. Our
      results suggest that cessation of the GnRH antagonist on the day of hCG
      administration during a flexible multiple-dose protocol could reduce the total
      dose of GnRH antagonist without compromising IVF results.

PMID- 19399269
TI  - Clinical features and outcomes of microscopic polyangiitis in Korea.
AB  - Microscopic polyangiitis (MPA) is a systemic vasculitis affecting small vessels.
      To determine the clinical features and outcomes of MPA in Korean patients, we
      retrospectively reviewed the medical records of patients diagnosed with MPA at a
      single medical center in Korea between 1989 and 2006. The 18 patients who met the
      Chapel Hill criteria for MPA had a mean (+/-SD) age at the time of diagnosis of
      62.4+/-12.7 yr. Renal manifestations and general symptoms were the most common
      features of MPA, with lung involvement also very common. Antineutrophil
      cytoplasmic antibodies (ANCA) were present in 17 of the 18 patients (94%). Of 17
      patients treated with steroids and cyclophosphamide, 11 (65%) had stable or
      improved course. One patient treated with steroids without cyclophosphamide
      showed disease progression. Ten of the 18 patients (56%) died at a median follow
      up of 8 months. MPA in Korean patients was distinguished by a higher rate of lung
      involvement, especially alveolar hemorrhage, which was the leading cause of death
      in our patients. Korean patients were also older at MPA onset and were more
      likely positive for ANCA. Other overall clinical manifestations did not differ
      significantly.

PMID- 19399270
TI  - The role of whole-body FDG PET/CT, Tc 99m MDP bone scintigraphy, and serum
      alkaline phosphatase in detecting bone metastasis in patients with newly
      diagnosed lung cancer.
AB  - Bone scan (BS) and serum alkaline phosphatase (ALP) concentration are used to
      detect bone metastasis in malignancy, although whole-body fluoro-D-glucose
      positron emission tomography computed tomography (FDG PET/CT) is being used
      increasingly. But BS is still used for the detection of metastatic bone lesion.
      So we compared the usefulness of PET/CT, BS, and serum ALP in detecting bone
      metastases in patients with newly diagnosed lung cancer. The medical record
      database was queried to identify all patients with a new diagnosis of lung cancer
      between January 2004 and December 2005, who had a PET/CT, BS, and serum ALP
      before treatment. We retrospectively reviewed all patients' records and
      radiological reports. One hundred eighty-two patients met the inclusion criteria.
      Bone metastases were confirmed in 30 patients. The sensitivity values were 93.3%
      for PET/CT, 93.3% for BS, 26.7% for serum ALP concentration, and 26.7% for BS
      complemented with serum ALP concentration. The respective specificity values were
      94.1%, 44.1%, 94.1%, and 97.3%. The kappa statistic suggested a poor agreement
      among the three modalities. FDG PET/CT and BS had similar sensitivity, but PET/CT
      had better specificity and accuracy than BS. PET/CT is more useful than BS for
      evaluating bone metastasis. However, in the advanced stage, because of its high
      specificity, BS complemented with serum ALP is a cost-effective modality to avoid
      having to use PET/CT.

PMID- 19399271
TI  - Improvement of induction remission rate by modifying the dose of idarubicin for
      relapsed childhood acute lymphoblastic leukemia.
AB  - Relapse is the major cause of treatment failure in acute lymphoblastic leukemia
      (ALL), yet there is no established treatment for relapsed ALL. To improve the
      induction remission rate, we modified the dose of idarubicin in the original
      Children's Cancer Group (CCG)-1884 protocol, and retrospectively compared the
      results. Twenty-eight patients diagnosed with relapsed ALL received induction
      chemotherapy according to the CCG-1884 protocol. Complete remission (CR) rate in
      all patients after induction chemotherapy was 57%. The idarubicin 10 mg/m(2)/week
      group showed CR rate of 74%, compared with the 22% CR rate of the idarubicin 12.5
      mg/m(2)/week group (p=0.010). Remission failure due to treatment-related
      mortality (TRM) was 44% and 5.2% in the idarubicin 12.5 mg/m(2)/week and 10
      mg/m(2)/week groups, respectively (p=0.011). Overall survival (OS) and 4-yr event
      free survival (EFS) were 12.8% and 10.3%, respectively. OS and 4-yr EFS were
      higher in the idarubicin 10 mg/m(2)/week group (19.3% and 15.6%) than in the 12.5
      mg/m(2)/week group (0% and 0%). In conclusion, a modified dose of idarubicin from
      12.5 mg/m(2)/week to 10 mg/m(2)/week resulted in an improved CR rate in the
      treatment of relapsed ALL, which was due to lower TRM. However, despite improved
      CR rate with modified dose of idarubicin, survival rates were unsatisfactory.

PMID- 19399272
TI  - Effect of iron-chelator deferiprone on the in vitro growth of staphylococci.
AB  - The standard iron-chelator deferoxamine is known to prevent the growth of
      coagulase-negative staphylococci (CoNS) which are major pathogens in iron
      overloaded patients. However, we found that deferoxamine rather promotes the
      growth of coagulase-positive Staphylococcus aureus. Accordingly, we tested
      whether deferiprone, a new clinically-available iron-chelator, can prevent the
      growth of S. aureus strains as well as CoNS. Deferiprone did not at least promote
      the growth of all S. aureus strains (n=26) and CoNS (n=27) at relatively low
      doses; moreover, it could significantly inhibit the growth of all staphylococci
      on non-transferrin-bound-iron and the growth of all CoNS on transferrin-bound
      iron at relatively high doses. At the same doses, it did not at least promote the
      growth of all S. aureus strains on transferrin-bound-iron. These findings
      indicate that deferiprone can be useful to prevent staphylococcal infections, as
      well as to improve iron overload, in iron-overloaded patients.

PMID- 19399273
TI  - Acute pyelonephritis: clinical characteristics and the role of the surgical
      treatment.
AB  - The epidemiology of acute pyelonephritis (APN) has changed with time. Therefore
      we investigated the current clinical characteristics of APN and the significance
      of proper surgical management for treatment of 1,026 APN patients in South Korea
      for the past 5 yr. The male-to-female ratio was about 1:8. The peak ages of
      female patients were 20s (21.3%) and over 60s (23.7%), while that of male was
      over 60s (38.1%). The occurrence of sepsis was 10.1%. Complicated APN patients
      were 35.4%. Ninety-four patients (9.2%) needed urological procedures. The
      duration of the flank pain and of the costovertebral angle tenderness in
      complicated APN patients was statistically significantly longer than that with
      simple APN patients (4.3 vs. 3.4 days, 4.4 vs. 4.0 days). If flank pain and
      costovertebral angle tenderness sustain over 4 days, proper radiologic studies
      should be performed immediately with the consideration of surgical procedure.
      Also the resistance to antibiotics was increasing. As the sensitivities to
      ampicillin (27.2%) and trimethoprim/sulfamethoxazole (44.7%) of Escherichia coli
      and Klebsiella pneumoniae were very low, it is necessary to take the careful
      choice of antibiotics into consideration.

PMID- 19399274
TI  - Early outcome of posterior cervical endoscopic discectomy: an alternative
      treatment choice for physically/socially active patients.
AB  - Anterior cervical discectomy and fusion (ACDF) is currently the standard
      treatment for cervical disc disease. Some patients wish to be treated with a less
      invasive method, because of their social/physical situations. Here we present one
      method of treatments for socially/physically active patients. Three patients had
      triceps weakness and mild posterior neck pain. The offending lesions were at the
      C6-7 level. All were middle-aged soldiers with families. If conventional ACDF
      were performed, they would have to retire from the military according to the
      regulation. They had to be able to perform military drills after the treatment if
      they were going to be able to keep their jobs. Because of their social/physical
      situations, all wanted to choose method with that they could treat the disease
      and keep their jobs. For these reasons, the posterior cervical endoscopic
      discectomies were performed. Ruptured fragments were successfully removed in all.
      The arm pain improved by more than 90% in two patients by 7 days and in the other
      patient by 2 months, respectively (excellent outcome by Macnab's criteria). None
      of the operations caused instability. All of the patients are currently able to
      successfully perform their military drills without difficulty. The posterior
      cervical endoscopic discectomy may be a promising alternative for the
      physically/socially active patients.

PMID- 19399275
TI  - Phosphodiesterase 4D gene and risk of noncardiogenic ischemic stroke in a Korean
      population.
AB  - Recently published studies from different populations provide apparently
      conflicting evidence on the association between the phosphodiesterase 4D (PDE4D)
      gene and ischemic stroke. The relationship between a representative PDE4D
      genotype and ischemic stroke was explored in a case-control study of 205
      consecutive Korean patients with noncardiogenic ischemic stroke and 103 healthy
      controls who were neurologically and radiologically proven to be stroke-free. We
      selected and genotyped a PDE4D single nucleotide polymorphism (SNP 41, rs152312)
      as a candidate marker for susceptibility to ischemic stroke because SNP 41 has
      shown the most significant association with stroke in both a meta-analysis and
      the original Icelandic study of the PDE4D gene. No significant difference was
      observed between the cases and controls in the distribution of the PDE4D SNP 41
      genotypes. The results from the adjusted conditional logistic regression analysis
      (adjusted for age, hypertension, diabetes and smoking status) showed no
      significant association between PDE4D SNP 41 genotypes and an increased risk of
      noncardiogenic ischemic stroke. The PDE4D gene is not a major risk factor for
      noncardiogenic ischemic stroke in a Korean population, which supports the recent
      evidence suggesting that the causative genetic variants of ischemic stroke may
      differ across populations.

PMID- 19399276
TI  - Non-motor off symptoms in Parkinson's disease.
AB  - The aim of this study is to elucidate the clinical spectrum and frequency of non
      motor symptoms during off periods (NMOS) in Parkinson's disease (PD) patients
      with motor fluctuation. We compared clinical characteristics between PD patients
      with motor symptoms only (M-off) and those with both motor and non-motor symptoms
      (NM-off) during off periods. The association of NMOS with parkinsonian clinical
      characteristics was also investigated. Sixty-seven consecutive PD patients of
      both M-off and NM-off groups were included in this study. We reviewed medical
      records, interviewed the patients, and administered a structured questionnaire.
      NMOS is classified into three categories: autonomic, neuropsychiatric and
      sensory. The frequency of NMOS and their individual manifestations were assessed.
      Of 67 patients with off symptoms, 20 were M-off group and 47 NM-off group. Among
      NMOS, diffuse pain was the most common manifestation, followed by anxiety and
      sweating. There were no significant differences between M-off and NM-off groups
      with regard to age, duration of disease and treatment, interval between onset of
      parkinsonian symptoms and off symptoms and off periods. Patients taking higher
      dosage of levodopa had fewer NMOS. NMOS is frequent in PD. Comprehensive
      recognition of NMOS can avoid unnecessary tests and is important for optimal
      treatment in PD.

PMID- 19399277
TI  - Are portable imaging intraoperative radiographs helpful for assessing adequate
      acetabular cup positioning in total hip arthroplasty?
AB  - Despite advances in surgical techniques and instrumentation, current intra
      operative estimations of acetabular version in total hip arthroplasty are of
      limited accuracy. In the present study, two experienced orthopedic surgeons
      compared intra-operatively measured (using portable imaging) anteversions and
      vertical inclinations of acetabular components with those measured using
      standardized radiographs post-operatively in 40 patients. Of the all vertical
      inclinations measured from intra-operative radiographs, 72.5% (n=29) were within
      +/-2 degrees , and 97.5% (n=39) were within +/-5 degrees of those determined
      using post-operative radiographs, and for anteversion, 52.5% (n=21) were within
      +/-2 degrees , and 97.5% (n=39) were within +/-5 degrees . Post-operative
      radiographs demonstrated that 90.0% (n=36) of vertical inclinations and
      anteversions were within the adequate zone. Obviously, our method has its
      limitations, but the authors conclude that the method described in this article
      better allows surgeons to verify acetabular version intra-operatively. In
      particular, the described method is suitable in cases with a deformed acetabular
      anatomy and difficult revision surgery.

PMID- 19399278
TI  - Men's lower urinary tract symptoms are also mental and physical sufferings for
      their spouses.
AB  - Lower urinary tract symptoms (LUTS) in men may have an adverse effect on spouse
      health-related quality of life (HRQL), and these effects are probably influenced
      by cultural and perceptional differences. This study was conducted to explore the
      impact of LUTS in Korean men on their spousal HRQL in relation to symptom
      severities and other demographic parameters. A total of 130 spouses, whose
      husbands had a nocturia, frequency of greater than once per night, who shared a
      bed with their husbands, and accompanied husbands at consultation, were
      subsequently enrolled and asked to complete a structured questionnaire. Almost
      all spouses (98%) suffered one or more inconveniences that affected HRQL to some
      degree. Sleep disturbance was rated to be most inconvenient. The sleep
      disturbances were significantly correlated with nocturia frequency and husband co
      morbidity. Husband's LUTS caused partners to feel fatigued (62%), embarrassed
      (79%), concerned about the possibilities of cancer (69%) and surgery (81%),
      sexual life deteriorated (58%), and dissatisfied, unhappy, or terrible (36%).
      Spouse's perception on HRQL was found to be well correlated with husband's
      quality of life. Men with LUTS need to understand that their LUTS is also mental
      and physical sufferings for their spouses.

PMID- 19399279
TI  - Erosive arthropathy with osteolysis as a typical feature in polyfibromatosis
      syndrome: a case report and a review of the literature.
AB  - Polyfibromatosis syndrome is a rare disease entity that is characterized by
      various clinical features such as palmar, plantar, and penile fibromatoses,
      keloid formations of the skin, and erosive arthropathy. Its precise
      pathophysiology or etiology remains unclear. In addition to distinctive diverse
      skin manifestations, patients with polyfibromatosis have been previously reported
      to show erosive arthropathy with significant limitation of movement at affected
      joints. However, the presence of erosive polyarthropathy in polyfibromatosis has
      not emphasized in previous cases. Here, we report a case of polyfibromatosis
      syndrome combined with painless massive structural destruction of hand and foot
      joints, and review the characteristics of erosive arthropathy in previous cases.

PMID- 19399280
TI  - A case of successful surgical treatment of migraine headaches in a patient with
      sporadic pulmonary arteriovenous malformations.
AB  - Pulmonary arteriovenous malformations (PAVMs) are thin-walled aneurysms caused by
      abnormal communication between the pulmonary arteries and veins. Migraine
      headaches are sometimes the presenting clinical manifestation of PAVMs. Although
      embolotherapy, using detachable balloons or stainless steel coils, is generally
      accepted as the best choice for the treatment of multiple PAVMs, the mode of
      intervention for solitary PAVMs remains a subject of debate. We present a 43-yr
      old woman with a 10-yr history of chronic migraines and dyspnea on exertion. She
      was discovered to have a large solitary centrally located PAVM, placing her at
      high risk of complications if she were to undergo percutaneous transcatheter
      embolization. She underwent successful surgical resection of her right middle
      lobe without complications, resulting in subsequent symptomatic improvement.

PMID- 19399281
TI  - Giant mesenteric lipoma as an unusual cause of abdominal pain: a case report and
      a review of the literature.
AB  - We report a rare case of giant mesenteric lipoma presenting with colicky
      abdominal pain. A 29-yr-old woman underwent laparoscopic resection for a giant
      mesenteric lipoma causing compression of the ileal loop. The resected ileal
      segment was encased by a giant fatty tissue, and normal mucosal fold patterns of
      the resected ileum were effaced by the mass. Microscopically, the mass was
      characterized by homogenous mature adipose tissue without cellular atypia, which
      was compatible with the diagnosis of a mesenteric lipoma. Despite the benign
      nature of this tumor, total excision with or without the affected intestinal loop
      should be considered if intestinal symptoms such as abdominal pain are present.

PMID- 19399282
TI  - Granular cell tumor of the descending colon treated by endoscopic mucosal
      resection: a case report and review of the literature.
AB  - Although colorectal granular cell tumors (GCTs) are rare, their incidental
      finding has increased as the use of diagnostic colonoscopy has become more
      common. Here we describe the case of a 41-yr-old man with a GCT in the descending
      colon that was detected after a screening colonoscopy. Endoscopic examination
      revealed a yellowish submucosal tumor, 13x12 mm in diameter, in the descending
      colon. Endoscopic mucosal resection (EMR) followed by histological examination
      revealed that the tumor was composed of plump histiocyte-like cells with an
      abundant granular eosinophilic cytoplasm and small round nuclei. The tumor cells
      expressed S-100 protein and stained with periodic acid-Schiff, but were negative
      for desmin and cytokeratin. The resected tumor was diagnosed as a GCT.
      Colonoscopists should consider the possibility of GCT in the differential
      diagnosis of yellowish submucosal tumors of the colon. In such patients, EMR
      seems to be a feasible and safe approach for diagnosis and treatment.

PMID- 19399283
TI  - Cecal polypoid arteriovenous malformations removed by endoscopic biopsy.
AB  - Colonic arteriovenous malformation (AVM) is one of the causes of lower
      gastrointestinal bleeding. Unlike small vascular ectasia or angiodysplasia,
      colonic AVM tends to be solitary, large in size, and identified endoscopically as
      flat or elevated bright red lesion. Herein, we report a case of non-solitary and
      small cecal AVMs which were removed by endoscopic biopsy. A 66-yr-old woman was
      referred for routine gastrointestinal cancer screening. She was suffering from
      diabetes, hypertension, end-stage renal disease, and anemia of chronic disease.
      On colonoscopic finding, three semi-pedunculated polyps, less than 5 mm in size,
      were noticed near to the appendiceal orifice. Since the lesions revealed normal
      looking epithelium with converging folds on the cecal base, lesions were
      diagnosed as inflammatory polyps on gross finding. Three biopsies were taken from
      each lesion. Bleeding from the biopsied site ceased spontaneously.
      Histopathologic evaluation demonstrated intramucosal hemorrhage and dilated
      submucosal vessels which were consistent with polypoid colonic AVMs.

PMID- 19399284
TI  - Perivascular epithelioid cell tumor (PEComa) of abdominal cavity from falciform
      ligament: a case report.
AB  - We present a case of perivascular epithelioid cell tumors (PEComas) in the
      abdominal cavity at the falciform ligament. A 30-yr-old Korean man visited to
      hospital for the evaluation of a growing, palpable abdominal mass. He had felt
      the mass growing over 6 months. There was no family or personal history of
      tuberous sclerosis. The resected specimen showed a mass of 8.0x7.0x5.5 cm in
      size. Histological examination showed sheets of spindle-to-epithelioid cells with
      clear-to-eosinophilic cytoplasm. Immunohistochemically, tumor cells were positive
      for HMB-4 (gp100) and smooth muscle actin. They were also positive for the S-100,
      which is a marker of neurogenic and melanocytic tumors. Patient was treated with
      radical resection of tumor without any adjuvant therapy. He is well and on follow
      up visits without tumor recurrence.

PMID- 19399285
TI  - Loss of distal femur combined with popliteal artery occlusion: reconstructive
      arthroplasty using modular segmental endoprosthesis: a case report.
AB  - Severe injury to the knee and the surrounding area is frequently associated with
      injury to ligaments of the knee joint and structures in the popliteal fossa. This
      case involved a popliteal artery occlusion, severe bone loss of distal femur,
      loss of collateral ligaments, and extensor mechanism destruction of the knee.
      Initially, prompt recognition and correction of associated popliteal artery
      injury are important for good results after treatment. After successful
      revascularization, treatment for severe bone loss of distal femur and injury of
      the knee joint must be followed. We treated this case by delayed reconstruction
      using modular segmental endoprosthesis after revascularization of the popliteal
      artery. This allowed early ambulation. At 36 months after surgery, the patient
      had good circulation of the lower limb and was ambulating independently.

PMID- 19399286
TI  - A case of cardiac dysfunction associated with monoclonal gammopathy of
      undetermined significance.
AB  - The monoclonal gammopathies (MG) are monoclonal neoplasms related to each other
      by virtue of their development from common progenitors in the B lymphocyte
      lineage. Cardiac dysfunction in patients with MG is not well established. We
      experienced a case of cardiac dysfunction associated with MG identified by
      echocardiography and biopsy. Fifty nine year-old man was admitted because of
      dyspnea for several months. Echocardiography revealed diastolic dysfunction
      showing restrictive physiology with elevated left ventricular filling pressure.
      Bone marrow (BM) studies and immunoelectrophoresis were compatible with
      monoclonal gammopathy of undetermined significance. Endomyocardial, BM, and
      enteral biopsies for ruling out for amyloidosis (Congo-red stain) were negative.
      This is the case of non-amyloidotic light chain deposition cardiomyopathy.

PMID- 19399288
TI  - Zero tolerance policies toward adverse outcomes during labor and delivery: don't
      forget about the pilot.

PMID- 19399287
TI  - Massive empyema associated with transient hypogammaglobulinemia of infancy and
      IgA deficiency.
AB  - Transient hypogammaglobulinemia of infancy (THI) is originally defined as a
      physiological maturation defect of immunoglobulin G (IgG) production that occurs
      at 3-6 months of age and lasts until 18 to 36 months of age. We report here on a
      22-month-old child with THI and IgA deficiency, who had massive pneumococcal
      empyema. Her depressed IgG level returned to normal within 6 months, but IgA
      level was still low at 6 yr of age. Although THI is an age-dependent and self
      limiting disorder, severe infection that includes an atypical presentation of an
      infection may occur in some patients and this requires evaluation with
      immunologic study.

PMID- 19399289
TI  - Hyperreactio luteinalis with clitoromegaly in a twin pregnancy.

PMID- 19399291
TI  - InterStim Therapy: A Contemporary Approach to Overactive Bladder.
AB  - Overactive bladder is a common and challenging condition for the practicing
      obstetrician-gynecologist. The prevalence of the condition is increasing with our
      aging population. Although some patients respond to first-line therapy, a
      significant number will require sacral nerve stimulation to address the
      underlying neurologic condition that causes overactive bladder as well as other
      pelvic floor conditions. This article summarizes the epidemiology and
      symptomatology, office evaluation, and treatment of overactive bladder with
      particular emphasis on sacral nerve stimulation (SNS). SNS technique, results,
      and future applications are also reviewed.

PMID- 19399290
TI  - Vacuum-assisted vaginal delivery.
AB  - Approximately 5% (1 in 20) of all deliveries in the United States are operative
      vaginal deliveries. The past 20 years have seen a progressive shift away from the
      use of forceps in favor of the vacuum extractor as the instrument of choice. This
      article reviews in detail the indications, contraindications, patient selection
      criteria, choice of instrument, and technique for vacuum-assisted vaginal
      delivery. The use of vacuum extraction at the time of cesarean delivery will also
      be discussed. With vacuum extraction becoming increasingly popular, it is
      important that obstetric care providers are aware of the maternal and neonatal
      risks associated with such deliveries and of the options available to effect a
      safe and expedient delivery.

PMID- 19399292
TI  - Bacterial vaginosis: an overview for 2009.
AB  - Bacterial vaginosis has been appreciated as a unique clinical entity for well
      over 50 years. Its essential manifestations are well established: a loss of the
      normal bacterial population of the vagina and their replacement by other species.
      Investigations into this condition have led to a better understanding of its
      prevalence and epidemiology. Microbiologic and biochemical studies have exposed
      the remarkably complex pathophysiologic events that occur with bacterial
      vaginosis. Several major morbidities accompany this condition. Advances have been
      made in treatment, including the recent availability of a new therapeutic agent,
      tinidazole. However, the root cause of the condition is elusive, and as a result
      managing bacterial vaginosis and its complications is unsatisfactory; moreover,
      data suggest that therapy now is less successful than in the past. This article
      brings together the current fund of knowledge about bacterial vaginosis in a way
      that offers clinicians a realistic view of our capabilities and concerns.

PMID- 19399293
TI  - Preventing adhesions in obstetric and gynecologic surgical procedures.
AB  - Adhesive disease represents a significant cause of morbidity for postoperative
      patients. Most surgical procedures performed by obstetrician-gynecologists are
      associated with pelvic adhesions that cause subsequent serious sequelae,
      including small bowel obstruction, infertility, chronic pelvic pain, and
      difficulty in postoperative treatment, including complexity during subsequent
      surgical procedures. The technology of adhesion prevention has significantly
      progressed. There are 3 methods approved by the US Food and Drug Administration
      for the prevention of postoperative adhesions, including Adept((R)),
      Interceed((R)), and Seprafilm((R)). The latter barrier is the most widely
      studied. This article reviews the current choices available for adhesion
      prevention barriers as well as surgical adjuncts that traditionally have been
      studied for that purpose.

PMID- 19399294
TI  - Recent advances in tape slings for female urinary stress incontinence.
AB  - Sling therapy is the enhanced surgical support of the urethra. In this article,
      the history of the use of slings for the surgical treatment of female urinary
      stress incontinence is reviewed, and the usual surgical routes for retropubic
      (transvaginal) or transobturator tape passage are described. The latest
      innovation in sling therapy is the use of minislings, which are short tape mesh
      implants inserted through a single vaginal incision; these slings may be placed
      in an office setting. Outcomes data are either lacking or suggest a considerable
      decrement of effectiveness of unstabilized minislings over full-length slings;
      however, the short-term efficacy of a stabilized, adjustable minisling is 97%.
      These results suggest benchmark effectiveness associated with full-length slings
      in a less invasive device that also has the capability of short-term
      adjustability.

PMID- 19399295
TI  - Child marriage: a silent health and human rights issue.
AB  - Marriages in which a child under the age of 18 years is involved occur worldwide,
      but are mainly seen in South Asia, Africa, and Latin America. A human rights
      violation, child marriage directly impacts girls' education, health, psychologic
      well-being, and the health of their offspring. It increases the risk for
      depression, sexually transmitted infection, cervical cancer, malaria, obstetric
      fistulas, and maternal mortality. Their offspring are at an increased risk for
      premature birth and, subsequently, neonatal or infant death. The tradition,
      driven by poverty, is perpetuated to ensure girls' financial futures and to
      reinforce social ties. One of the most effective methods of reducing child
      marriage and its health consequences is mandating that girls stay in school.

PMID- 19399296
TI  - Total laparoscopic hysterectomy: 10 steps toward a successful procedure.
AB  - Vaginal and laparoscopic hysterectomies have been clearly associated with
      decreased blood loss, shorter hospital stay, speedier return to normal
      activities, and fewer abdominal wall infections when compared with abdominal
      hysterectomies. In this review, the authors outline the 10 steps to a successful
      laparoscopic hysterectomy.

PMID- 19399297
TI  - Testosterone and sexual desire.

PMID- 19399298
TI  - Hormonal contraception and bone mineral density.

PMID- 19399299
TI  - The effects of hormonal contraception.

PMID- 19399300
TI  - Why Doesn't a Mother Reject Her Fetus?

PMID- 19399301
TI  - Acne and new regimens.

PMID- 19399302
TI  - Snippets.

PMID- 19399303
TI  - Chyloptysis with right middle lobe syndrome complicated postoperatively by
      chylothorax: an unusual cause of right middle lobe syndrome.
AB  - Chyloptysis, in the context of middle lobe syndrome, and chylothorax are rare
      clinical entities. They are reported in the medical literature mostly as case
      reports, but never together in the same patient. The present report describes the
      case of a 34-year-old woman who presented with chyloptysis associated with
      recurrent right middle lobe syndrome since she was 20 years of age, and
      eventually underwent right middle lobectomy. A few weeks postoperatively, she
      developed a right-sided chylothorax, which was refractory to medical therapy, and
      was successfully treated with thoracic duct ligation. She has been symptom-free
      for two years postsurgery.

PMID- 19399304
TI  - Acute lung injury during antithymocyte globulin therapy for aplastic anemia.
AB  - The case of a 33-year-old man with aplastic anemia who experienced recurrent
      episodes of hypoxemia and pulmonary infiltrates during infusions of antithymocyte
      globulin (ATG) is described. With the use of high-dose corticosteroids, the
      patient's original episodes resolved, and were subsequently prevented before
      additional administrations of ATG. Rare reports of an association between ATG and
      acute lung injury are found in the literature, but this is the first report of
      successful steroid-supported re-exposure. Although the mechanism of ATG-related
      acute lung injury remains uncertain, it may be parallel to the mechanism of
      transfusion-related acute lung injury because the pathogenesis of the latter
      relies, in part, on antileukocyte antibodies. ATG-related toxicity should be
      included in the differential diagnosis of new, infusion-associated pulmonary
      infiltrates, and corticosteroids may be a useful therapeutic consideration in the
      management.

PMID- 19399306
TI  - Efficient management of cough.

PMID- 19399307
TI  - Amiodarone pulmonary toxicity.
AB  - Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and
      ventricular arrhythmias. This drug is an iodinecontaining compound that tends to
      accumulate in several organs, including the lungs. It has been associated with a
      variety of adverse events. Of these events, the most serious is amiodarone
      pulmonary toxicity. Although the incidence of this complication has decreased
      with the use of lower doses of amiodarone, it can occur with any dose. Because
      amiodarone is widely used, all clinicians should be vigilant of this possibility.
      Pulmonary toxicity usually manifests as an acute or subacute pneumonitis,
      typically with diffuse infiltrates on chest x-ray and high-resolution computed
      tomography. Other, more localized, forms of pulmonary toxicity may occur,
      including pleural disease, migratory infiltrates, and single or multiple nodules.
      With early detection, the prognosis is good. Most patients diagnosed promptly
      respond well to the withdrawal of amiodarone and the administration of
      corticosteroids, which are usually given for four to 12 months. It is important
      that physicians be familiar with amiodarone treatment guidelines and follow
      published recommendations for the monitoring of pulmonary as well as
      extrapulmonary adverse effects.

PMID- 19399308
TI  - Assessment and management of patients with chronic cough by Certified Respiratory
      Educators: a randomized controlled trial.
AB  - BACKGROUND: The value of other health care professionals is increasingly being
      recognized to compensate for the shortage of physicians in Canada. Chronic cough
      is one of the most common reasons for consultation with a respirologist. In the
      present study, a prospective, randomized, controlled study was undertaken to
      determine whether Certified Respiratory Educators (CREs) could manage screened
      patients with chronic cough as effectively as respirologists. METHODS: An eight
      week, prospective, parallel-design, randomized, controlled trial of the
      management of chronic cough patients was conducted. Patients were screened to
      exclude those with potentially life-threatening conditions. The primary outcome
      was the number of patients whose cough resolved or subjectively improved.
      RESULTS: A total of 198 patients were randomly assigned, and eight-week data were
      available on 151 patients. Mean age of the patients was 49.8+/-13.4 years, 70.2%
      were female and median cough duration was 16 months. The screening process was
      effective and referral wait times decreased from a median of two months to less
      than four weeks (P<0.0001). The educators averaged 4.9 contacts per patient
      compared with 2.7 by the physicians over the eight-week study period (P<0.0001).
      Most patients had had multiple therapeutic trials before referral. Cough resolved
      or improved in two-thirds of the patients at eight weeks; however, more patients
      showed improvement in the educator arm than in the physician arm, P<0.02. Cough
      specific quality of life improved similarly in the two study arms at eight weeks
      (physician arm: 61.5+/-14.1 to 52.6+/-14.4, P<0.0001; CRE arm: 58.1+/-14.9 to
      50.0+/-15.8, P=0.0003). CONCLUSIONS: CREs can safely and effectively assess, as
      well as appropriately treat, screened patients with chronic cough with a
      resultant reduction in wait times.

PMID- 19399309
TI  - An evaluation of procedural training in Canadian respirology fellowship programs:
      program directors' and fellows' perspectives.
AB  - BACKGROUND: In recent years, there has been a rapid growth in diagnostic and
      therapeutic procedures performed by respirologists. OBJECTIVES: To assess the
      number and type of procedures performed in Canadian respirology training
      programs, for comparison with the American College of Chest Physicians minimum
      competency guidelines, and to assess fellow satisfaction with procedural training
      during their fellowships. METHODS: Internet-based surveys of Canadian respirology
      fellows and respirology fellowship program directors were conducted. RESULTS:
      Response rates for program director and respirology fellow surveys were 71% (10
      of 14) and 62% (41 of 66), respectively. Thirty-eight per cent of respirology
      fellows reported the presence of an interventional pulmonologist at their
      institution. Flexible bronchoscopy was the only procedure reported by a large
      majority of respirology fellows (79.5%) to meet American College of Chest
      Physicians recommendations (100 procedures). As reported by respirology fellows,
      recommended numbers of procedures were met by 59.5% of fellows for tube
      thoracostomy, 21% for transbronchial needle aspiration and 5.4% for closed
      pleural biopsy. Respirology fellows in programs with an interventional
      pulmonologist were more likely to have completed some form of additional
      interventional bronchoscopy training (80% versus 32%; P=0.003), had increased
      exposure to and expressed improved satisfaction with training in advanced
      diagnostic and therapeutic procedures, but did not increase their likelihood of
      achieving recommended numbers for any procedures. CONCLUSIONS: Canadian
      respirology fellows perform lower numbers of basic respiratory procedures, other
      than flexible bronchoscopy, than that suggested by the American College of Chest
      Physicians guidelines. Exposure and training in advanced diagnostic and
      therapeutic procedures is minimal. A concerted effort to improve procedural
      training is required to improve these results.

PMID- 19399310
TI  - HIV/AIDS and Indian youth--a review of the literature (1980-2008).
AB  - The main objective of this article is to provide a comprehensive overview of the
      situation regarding HIV/AIDS among youth in India, and explore the possible
      strategies that could be effective in combating the spread of this disease. India
      is in the grip of the HIV/AIDS epidemic, with an increasing number of infections
      being reported among youth, who comprise a quarter of the population but account
      for almost one-third of the HIV/AIDS burden. The prevalence in young women
      appears to be on the rise. Although the majority of youth are aware of the
      disease, a number of myths and misconceptions still prevail. Furthermore, or as a
      consequence, a higher percentage of young males report engaging in premarital
      sexual activity compared with females. Even though condom awareness is fairly
      high, condom usage is low. Of late, sex tourism and its implications for the
      HIV/AIDS epidemic present an increasing concern. Indian youth appear to hold
      negative attitudes towards HIV testing and people living with HIV/AIDS. Although
      a number of preventive and control programmes and policies exist, these need
      further strengthening and evaluation.

PMID- 19399311
TI  - Correlates of condom use among sexually experienced secondary-school male
      students in Nairobi, Kenya.
AB  - This study aimed to examine perceptual factors associated with condom use, and
      the relationship between condom use and the timing of sexual debut among male
      secondary school students in Nairobi, Kenya. Data are from the TeenWeb study, a
      school-based project that used the World Wide Web to assess the health needs of
      secondary school students, and tested the web's utility as a teaching and
      research modality. Analyses are based on 214 sexually experienced males aged 14 -
      20 years who completed web-based questionnaires about their sexual attitudes and
      behaviour. Results indicate that students did not see themselves as susceptible
      to HIV/AIDS and believed condom effectiveness in preventing HIV to be low.
      Consequently, only a marginal association was found between agreeing that buying
      condoms is embarrassing and condom use at first sexual intercourse. However,
      contrary to expectation, agreeing that condoms often break (almost half of
      participants) was associated with a higher likelihood of condom use at first sex.
      Each year of delay in sexual debut increased the likelihood of using a condom at
      first sex by 1.44 times. In turn, having used a condom at first sex increased the
      likelihood of using one at the most recent sex by 4.81 times, and elevated
      general condom use ('most or all the time') by 8.76 times. Interventions to
      increase awareness about the role of condoms in preventing HIV, delay sexual
      initiation, and teach proper condom use among secondary-school students in
      Nairobi are needed.

PMID- 19399312
TI  - Attitude of health care workers to patients and colleagues infected with human
      immunodeficiency virus.
AB  - Discrimination against persons living with HIV/AIDS in hospital settings has been
      documented. This study examined the attitude of health care workers (HCWs) to
      nurses, doctors and patients infected with HIV. A total of 345 respondents
      selected by multistage sampling techniques were surveyed, using a semi-structured
      questionnaire, which explored respondents' attitude to HIV-infected patients and
      colleagues with HIV/AIDS. HCWs were unwilling to accept that medical procedures
      be carried out on them by HIV-infected doctors and nurses, with almost 80%
      refusing surgery or assistance at surgery on them by an HIV-infected doctor or
      nurse. They were also significantly more unwilling to accept that medical
      procedures be carried out on them by an infected colleague, compared with their
      carrying out the same procedure on an HIV-infected patient. Thus, HCWs seemed to
      believe that the risk of contracting HIV was higher if an infected HCW were to
      perform medical procedures on them, and fear of contracting HIV seemed to be the
      driving force for their negative attitudes. Education on occupational risks of
      HIV, provision of a safe working environment with enforcement of universal
      precautions, as well as provision of post-exposure prophylaxis are suggested as
      ways to enable HCWs to change their attitudes.

PMID- 19399313
TI  - Challenges impacting on the quality of care to persons living with HIV/AIDS and
      other terminal illnesses with reference to Kanye community home-based care
      programme.
AB  - HIV/AIDS has been found to be a challenging disease to humanity, its challenge
      spin-offs falling especially on to the caregivers of those infected and affected
      by the virus. This paper aims to discuss the challenges influencing the state of
      caregiving in the Kanye community home-based care (CHBC) programme in Botswana.
      The study was qualitative in design and explorative in nature, involving 82
      primary caregivers in focus group discussions, and 5 CHBC nurses in individual
      interviews. Caregivers were found challenged by lack of community networks
      support, inadequate sanitary and care packages, poor shelter compromising
      privacy, inadequate income and food for their clients, inadequate care motivation
      as their volunteerism does not attract any payment, inadequate health personnel
      to offer psychosocial support like counselling, and an unconducive caring
      environment generally. Putting in place policies to redress caregivers' poverty,
      helping caregivers start income-generating projects, increasing community
      assistance and caregiving facilities are recommended as factors to address
      caregiver challenges.

PMID- 19399315
TI  - [Plagiarism in scientific publications].
AB  - Similar to what occurs in literature, art and other human endeavours, every
      scientific report is based in previous work done by others. The new paper should
      add something original but a basic law of scientific honesty demands that any
      mention ideas, observations or thinking that has been previously proposed or
      published by others, should be acknowledged properly in the text and in the
      references. Plagiarism is identified when the authors of a scientific report use
      ideas or text that belong to others and present them as original, the previous
      source is concealed or it is referred to in a different context. The authors of a
      paper that contains plagiarism have the intention to mislead the readers,
      pretending to be the original authors of an idea that was expressed previously by
      others, or to be the owners of results shown by them. Plagiarism is a dishonest
      behaviour and, when discovered, may have dangerous consequences because the
      editors of the journal may publish a notice of retraction that will be inserted
      by Medline in both papers: the plagiarized and the plagiarizer, to be noticed by
      everyone who accesses to either of them in the Internet.

PMID- 19399314
TI  - Military men and sexual practices: discourses of 'othering' in safer sex in the
      light of HIV/AIDS.
AB  - Despite recent reports that there is increasing condom use, generally resistance
      to condom use is still high. This paper focuses on factors inhibiting condom use
      and explores issues of responsibility for safe sex practices to prevent infection
      among a group of 14 South African male soldiers. Military men are particularly
      vulnerable to HIV because of their working conditions; for example, working far
      from home and being among communities where they have greater economic and
      political power, as well as in relation to their identities and sexualities as
      men, and how that is exaggerated by the institutional framework of the military.
      The data in this paper were drawn from a larger qualitative study exploring a
      group of military men's narratives on their masculinity, sexuality, sexual
      relationships and HIV/AIDS. Semi-structured interviews were the main data
      collection method, and the interview transcripts were analysed primarily through
      interpretive discourse analysis. Findings of this study show that most
      participants used the socially desirable discourse that safe sex practices
      (specifically condom use) should be everybody's responsibility. However, there
      was also the discourse of the 'other' responsible person, which was linked to
      gender, race, ethnicity, education and rank. The paper concludes with a
      recommendation that tackling HIV in the military needs to involve the rigorous
      examination of social factors such as gender, race and ethnicity.

PMID- 19399316
TI  - [Adverse reactions to diphtheria-pertussis-tetanus vaccine in the Chilean
      Immunization Program].
AB  - BACKGROUND: During 2005, the surveillance system of the Chilean Immunization
      Program detected an increased number of adverse reaction notifications associated
      to diphtheria, pertussis and tetanus whole-cell vaccine (DPT), coincidently with
      a change in the vaccine manufacturer. AIM: To compare the reactogenicity of two
      DPT formulations (vaccines 1 and 2) in 18-month-old infants and 4-year-old
      children. MATERIAL AND METHODS: Severe adverse reactions to DPT were studied at
      the emergency room of two hospitals of Santiago in a case-control study (110
      cases and 171 controls, who consulted for other causes). Simultaneously the
      incidence of total adverse reactions (mild and severe) for vaccine 1 and 2 was
      estimated in a cohort of 1,017 children vaccinated in an ambulatory health center
      of the same area. The formulation of DPT received by all participants was
      verified, as well as the temporal relation with consultation or symptoms referred
      by their caregivers. RESULTS: There was a greater probability of consulting at
      the emergency rooms for severe adverse reactions among children who received
      vaccine 1 (odds ratio (OR) =7.1; p <0.001), being greater among 4-year-old
      children (OR =18.9; p <0.001). Coincidently, in the cohort of vaccinated
      children, those who received vaccine 1 had a higher risk of presenting adverse
      reactions (RR =2.9; p <0.001), being high fever the commonest. CONCLUSIONS: We
      confirmed that vaccine 1 was associated to a higher risk of adverse reactions,
      especially among 4-year-old children. These results allowed the sanitary
      authority to adopt an informed decision. The usefulness of observational studies
      in vaccine adverse reactions is confirmed.

PMID- 19399317
TI  - [Beating heart anterior descending coronary artery grafting with left internal
      mammary artery: a long term follow up experience].
AB  - BACKGROUND: In recent years the use of left internal mammary artery (LIMA) as a
      gran to anterior descending artery (DA) with the off pump technique has been
      associated with similar good long term results as with the on pump technique.
      AIM: To report the results of LIMA to DA bypass grafting without extracorporeal
      circulation (EC) for isolated DA lesions. PATIENTS AND METHODS: Descriptive study
      of 80 patients subjected to coronary surgery between 1999 and 2007. RESULTS: Mean
      age of patients was 63 + 10 years and 60 were male. There was no operative
      mortality or stroke. One patient with a myocardial infarction required a
      reoperation. Actuarial survival was 98% at 97 months. CONCLUSIONS: In this group
      of patients the use of LIMA as a coronary bypass gran to DA with the off pump
      technique is a safe surgical procedure, providing a prolonged cardiac event free
      survival (mortality, angina, myocardial infarction, and need for a new coronary
      procedure).

PMID- 19399318
TI  - [Surgery of post myocardial infarction papillary muscle rupture].
AB  - BACKGROUND: Papillary muscle rupture is a serious complication of myocardial
      infarction whose only treatment is surgery. AIM: To analyze our most recent
      surgical experience with papillary muscle rupture. PATIENTS AND METHODS: The
      database of our Service was reviewed for the period 1995-2005, to identify
      patients with papillary muscle rupture. Then, the clinical records and operating
      protocols were analyzed. Survival and functional class of patients were assessed.
      RESULTS: Twelve patients (7 men), aged 52 to 89 years, had papillary muscle
      rupture. They represented 2.2% of all mitral procedures for mitral insufficiency
      and 8.8% of mitral surgeries for ischemic mitral regurgitation, during the study
      period. In eight cases myocardial infarction was inferior, in three lateral and
      in one, anterior. In 10 patients, a mitral replacement was carried-out and in two
      the mitral valve was repaired. In seven patients, myocardial revascularization
      was performed. Mean lapse between infarction and surgery was 13.5 days (1 to 85).
      Two patients died in the perioperative period. Follow-up ranged from 1.7 to 120.4
      months. Four patients died during follow-up, 2 due to a cardiovascular cause.
      Thus, at the end of follow-up 6 patients were alive. All were in functional class
      I-II. CONCLUSIONS: Papillary muscle rupture is an uncommon complication of
      myocardial infarction, with considerable operative and long-term mortality.
      However, survivors have good quality of life.

PMID- 19399319
TI  - [Precocious pubarche: experience in 173 cases ].
AB  - BACKGROUND: Precocious pubarche (PP), defined as the development of sexual pubic
      hair before 8 years of age in females and before 9 years in males, is usually a
      benign condition but it can also be the first sign of an underlying disease. AIM:
      To analyze the etiology and perform a short term follow up in a cohort of
      patients with PP. MATERIAL AND METHODS: A group of 173 patients (158 females)
      consulted for PP with a mean age of 7.4+/-0.1 years. These patients were followed
      between 15 to 60 months. Anthropometric measurements, bone age, serum levels of
      total testosterone, 17 OH progesterone (17 OHP) and dehydroepiandrosterone
      sulphate (DHEAS) were evaluated. RESULTS: Mean birth weight and length was
      3024.1+/-50.5 g and 48.5+/-0.3 cm, respectively. Ten percent of children were
      small for gestational age at birth. Bone age was accelerated by 1.1+/-0.01 years.
      One hundred and twelve patients were classified as having idiopathic PP (64.7%;
      105 females), 29 as central precocious puberty (16.8%; only females), 16 as
      exaggerated adrenarche (EA 9.2%; 13 females) and 16 as non classical adrenal
      hyperplasia (9.2%; 11 females). CONCLUSIONS: PP represents a common and usually
      benign sign. However, 26% of cases had a pathologic underlying condition.
      Therefore, all children with PP should be evaluated by a pediatric
      endocrinologist. Low birth weight was not frequent in this cohort and these
      patients did not show EA .

PMID- 19399320
TI  - [Blood pressure and family history of hypertension in children from Santiago,
      Chile].
AB  - BACKGROUND: The prevalence of pediatric arterial hypertension (AHT) is
      approximately 1% to 2%. In the last tenyears, mean blood pressure levels (BP)
      have raised due to obesity and changes in lifestyles. Family history (FH) of AHT
      is a risk factor to develop AHT in children. AIM: To assess blood pressure,
      cardiovascular risk factors and family history in healthy children of Santiago.
      MATERIAL AND METHODS: Blood pressure, family history of AHT, birth weight (BW),
      gestational age, puberal stage, blood glucose, serum lipids and ultrasensitive
      Reactive C Protein (usCRP) were analyzed, using data from a study of early
      markers of atherosclerosis in children. RESULTS: Data of 112 children aged
      between 6-12 years was analyzed. Hypertension (BP >percentile 95) was detected in
      2.7% and pre hypertension (BP in percentiles 90-95) in 3.6% of the sample.
      Children with abnormal BP had higher levels of usCRP (p <0.05) and a non
      significant tendency towards a higher body mass index. All hypertensive and one
      pre hypertensive children had FH of AHT. Eleven percent of parents, had high
      blood pressure. In no children, both parents were hypertensive. Children with a
      family history of hypertension had higher concentrations of total serum
      cholesterol (p <0.05). CONCLUSIONS: The abnormal prevalence of AHT found in this
      study is comparable to other studies. FH associated to higher levels of BP in
      children. Children with abnormal BP had a higher subclinical level of
      inflammation .

PMID- 19399321
TI  - [Unwanted pregnancy and access to printed media in Peruvian women].
AB  - BACKGROUND: It is possible that there is a relationship between reading
      newspapers and magazines, watching television and inverted exclamation listening
      to the radio and unwanted pregnancies. AIM: To assess the relationship between
      the access to printed and audiovisual information resources and unwanted
      pregnancy in Peruvian women. MATERIAL AND METHODS: A sample of 5,071 women, aged
      between 18 and 30 years was selected from a database of a Demographics and Health
      survey performed between 2004 and 2005. Using the information obtained in the
      survey, the association between unwanted pregnancies and reading newspapers and
      magazines, was analyzed. RESULTS: Twenty six percent of women had at least an
      unwanted child (n =1,327). Radio and television were the media mostly used by
      these women. Seventy five percent of women almost never read newspapers and
      magazines. The lack of reading and the reliance in television and radio as
      sources of information were all associated with unwanted pregnancy (p < 0.001).
      CONCLUSIONS: In this sample of women, there is a negligible interest for reading
      and a high preference for radio and television. This explains the poor knowledge
      on sexual and reproductive health and the lack of impact of printed materials
      used in educational campaigns.

PMID- 19399322
TI  - [Possible role of psychological and environmental factors in the genesis of
      childhood vitiligo].
AB  - BACKGROUND: The exposure to stressing situations may play a role in the
      appearance of vitiligo. Patients with the disease have a greater sensitivity to
      environmental stress and a lower threshold to generate catecholamine mediated
      responses. AIM: To evaluate the temperament and character of patients with
      vitiligo and explore the relationship of the disease with negative life events
      and life quality impairment. MATERIAL AND METHODS: The study population were 21
      patients with vitiligo aged 5 to 12 years, and two control groups (Gl and G2). Gl
      was composed by 14 healthy siblings of vitiligo patients. G2 was composed by 21
      age and gender matched healthy students from two schools in Santiago, Chile. The
      Junior Temperament and Character Inventory (JTCI), the Qualitative Psychosocial
      Development Survey (QPDS), the Life Event Checklist (LEC) and the Children's Life
      Quality index (CDLQI) were applied (LEC only to vitiligo patients). RESULT: On
      the temperament dimensions, vitiligo patients scored high on the "harm avoidance"
      scale in comparison to G2 (13.7 v/s 10.6). Compared with Gl, QPDS showed in
      vitiligo patients a higher frequency of fear to strangers (71% and 36%,
      respectively) and a predominant feeling of fear and shyness in response to
      changes in a close relative (80% and 8%, respectively). There was a negative
      correlation (protective factor) between the character dimension "self
      directedness" and CDLQI score (r =-0.703). CONCLUSIONS: In this group of
      patients, we found a possible relationship between a specific temperament
      dimension, vitiligo and its impact on life quality.

PMID- 19399324
TI  - [Molecular subtyping of Salmonella enterica serotype Enteritidis in a post
      epidemic period].
AB  - BACKGROUND: In the last two decades, Salmonella enterica serotype Enteritidis has
      become one of the main agents causing food borne diseases worldwide. This agent
      is transmitted mainly by contaminated meat and poultry. AIM: To determine the
      genetic subtypes of Salmonella enterica serotype Enteritidis, circulating in
      Chile between 2001 and 2003, a post epidemic period. MATERIAL AND METHODS: One
      hundred ninety three isolates coming from human samples, prepared foods and
      animal products for human consumption, were analyzed by pulsed field
      electrophoresis, using PulseNet standardized protocol. RESULTS: Thirteen subtypes
      of Salmonella enterica serotype Enteritidis were identified, that had between 0
      and 13 bands. A predominant subtype was identified in 172 strains (88%) that came
      from human isolates, prepared foods and animal products for human consumption.
      Other four subtypes, found in prepared foods and animal products for human
      consumption, were also found in human isolates. Most subtypes were tightly
      interrelated Subtypes II, VIII and XI were also found in the 1994 epidemic.
      CONCLUSIONS: Subtyping of bacterial strains by pulsed field electrophoresis is
      useful for the surveillance of food borne diseases.

PMID- 19399323
TI  - [Interleukin-1 genetic polymorphism: association with gastric cancer in the high
      risk Central-Western population of Venezuela].
AB  - BACKGROUND: Genetic predisposition may play a role in the prevalence of gastric
      cancer (GC). AIM: To investigate the relationship between selected interleukin-1
      (IL-1) loci polymorphisms and gastric cancer risk in the Central-Western region
      of Venezuela, where gastric cancer represents the first cause of cancer-related
      deaths. MATERIAL AND METHODS: In a case-control study we compared the frequencies
      of IL-1B-511 and IL-1B+3954 biallelic polymorphism, and the pentallelic VNTR of
      IL-IRN in 84 gastric adenocarcinoma paraffin-embedded biopsies and 84 endoscopic
      biopsies from cancer-free controls. RESULTS: No significant increase in genotypic
      frequencies in gastric cancer was observed for any of the IL-1B-511 allelic
      combinations. However, in a logistic regression analysis, a significant
      association emerged for the IL-1B+3954C carrier genotype (odds ratio (OR): 6.2;
      95% confidence intervals (CI) 1.3-28.8). On the other hand, a significantly
      higher risk was evidenced for the IL-IRN*2/*2 genotype (OR: 7.0; 95% CI2.3-21.5).
      Only patients with a well/moderately-differentiated adenocarcinoma that were
      homozygotes for the E-IRN*2/*2 genotype, had a higher risk than the complete
      gastric cancer group (OR: 8.1, 95% CI 2.5-26.8). Some genotype combinations among
      IL-1B-511, IL-1B+3954 and IL-IRN showed an increased risk for developing gastric
      cancer and well/moderate differentiated adenocarcinoma, that was dependent of the
      presence of IL-IRN*2/*2 genotype. CONCLUSIONS: IL-IRN*2/*2 genotype is associated
      with increased risk of gastric cancer in the Venezuelan population.

PMID- 19399325
TI  - [Discordance between nutritional status and self perception of weight among
      adults from Talca, Chile].
AB  - BACKGROUND: Obesity is related to underestimation of one's own weight. AIM: To
      determine the agreement between nutritional status and self perception of weight
      status in apparently healthy adults from Talca. SUBJECTS AND METHODS: Data were
      obtained from a survey applied at 1007 randomly selected subjects, aged 18-74
      years old (66% women). The survey identified age, gender, educational level and
      socioeconomic status. Self-perception of weight was estimated with pictures
      representing the four nutritional status categories: underweight, normal,
      overweight and obese. Body Mass index (BMI, kg/m(2)) was calculated to determine
      nutritional status. Statistical analysis included kappa index, Bowman s symmetry
      test and a logistic regression model to calculate the odds ratio in different
      variables related to underestimation of weight. RESULTS: Seventy three percent of
      subjects were overweight or obese and 44% underestimated their nutritional
      status. Sixty percent of subjects with a BMI between 25 and 26 kg/m(2), perceived
      themselves as normal. A higher underestimation was observed in obese subjects
      (odds ratio (OR) 17.2 95% confidence intervals (CI) 10.9-27.1), in overweight
      individuals (OR 3.5 95% CI 2.3-5.3), in men (OR 1.5 95% CI 1.1-2.1) and in people
      aged from 45 to 59 years (OR 1.7 95% CI 1.0-2.7). CONCLUSION: Almost half of
      studied population had an erroneous self-perception of weight, mainly due to
      underestimation. Obese subjects, males and people older than 45 years were those
      with the higher degree of underestimation.

PMID- 19399326
TI  - [Collision tumor consisting in a metastatic adenocarcinoma and follicular
      lymphoma in the same lymph node. Report of one case].
AB  - Collision tumors are defined as the simultaneous presence of two adjacent but
      histologically distinct tumor types arising in the same organ or site. The
      occurrence of these tumors is rare. We report a 52 year-old woman with a
      collision tumor consisting of metastatic adenocarcinoma and follicular lymphoma
      present in the same lymph node, excised from the left supraclavicular space. The
      patient died four weeks after the diagnosis was made.

PMID- 19399328
TI  - Down-Syndrome associated with MBL-deficiency, IgG-deficiency, vasculitis and
      mutated prothrombin.
AB  - The association of Down syndrome with mannose-binding lectin (MBL)-deficiency,
      recurrent infections and vasculitis has not been reported. We report a 30 year
      old female with Down-syndrome associated with MBL-deficiency with the genotype
      LXA/HYD, IgG-deficiency, recurrent uro-genital infections, cutaneous vasculitis,
      G20.210A prothrombin mutation, deep venous thrombosis, and pulmonary embolism.
      MBL-deficiency in combination with IgG deficiency might have favored the
      development of recurrent uro-genital infections. Immunodeficiency might be also
      involved in the pathogenesis of cutaneous vasculitis. Deep venous thrombosis and
      pulmonary embolism were attributed to the genetically determined prothrombotic
      state and intake of oral contraceptives.

PMID- 19399327
TI  - [Refractory dermatomyositis associated with chronic organizing pneumonia treated
      with rituximab: report of one case].
AB  - Chronic organizing pneumonia (COP) has often been reported as a pulmonary
      manifestation of collagen vascular diseases, mainly rheumatoid arthritis, but the
      association of COP and dermatomyositis (DM) has rarely been documented. We report
      a 55 year-old woman with well-documented DM and a COP. She was refractory to
      steroids and two other immunosuppressive agents therapy (cyclophosphamide and
      azathioprine). Therefore, rituximab (2 x 1 g infusions) was used for treatment.
      During the following weeks her strength gradually increased while creatine kinase
      (CK), C reactive protein and erythrocyte sedimentation rate normalized. After 6
      months, she had a relapse with increased muscle enzymes, fever and moderate
      muscle weakness. After a second course of rituximab (2 x 1 g infusions), the
      patient demonstrated a remarkable clinical response as indicated by an increase
      in muscle strength and moderate decline in creatine kinase levels. Lung
      abnormalities resolved significantly on high resolution chest CT scan. Thus, B
      cell depletion therapy with rituximab used alone or in combination with other
      immunosuppressants may be a viable option in patients with polymyositis
      dermatomyositis and pneumonia refractory to current therapies.

PMID- 19399330
TI  - [The relevance of environmental health and the scope of pediatric environmental
      health specialty units].
AB  - In the last decades there has been an important decrease in infant mobidity and
      mortality, but these achievements are not equally distributed across the whole
      population. Children are one of the most susceptible groups due to their unique
      vulnerabilities to environmental factors. Unhealthy environments, indoor
      pollution, poor drainage, inadequate waste disposal, and many others, are
      significant environmental risk factors to children. Currently, Chile is
      experiencing an advanced demographical transition, a situation that requires a
      precise approach to guarantee that the population has an adequate health status.
      It is important to take care of children, since their present health status will
      condition their health as adults. Pediatric Environmental Health Specialty Units
      are structures specialized in pediatric conditions related to the environment,
      formed by an interdisciplinary and highly specialized team. These centers provide
      assistance, information and treatment, promote research, educate health care
      providers or the public, and report problems to authorities. Health authorities
      should emphasize the importance of having a safe environment for children and
      encourage efforts to reduce exposure to environmental hazards promoting healthy
      behaviors, education and awareness at all levels of society .

PMID- 19399329
TI  - [Acute type A aortic dissection in pregnant patient with Marfan syndrome. Report
      of one case].
AB  - Aortic dissection is a life-threatening disease that requires immediate surgical
      intervention. Marfan syndrome is a hereditary disease with an autosomal dominant
      transmission, which affects the connective tissue, with skeletal, cardiovascular
      and ocular involvement. It is one of the most prevalent connective tissue
      disorders, presenting a risk of aortic dissection of approximately 1% even
      without dilatation of the aorta. When dissection occurs during pregnancy and
      requires surgical intervention (type A dissection), maternal mortality is high
      (2096-30%). We report a 38 year-old woman with Marfan syndrome that had an acute
      type A aortic dissection and severe aortic regurgitation at 37 weeks of
      gestation. The patient underwent a cesarean section and delivered a healthy baby.
      Afterwards, aortic valve repair and ascending aortic replacement was successfully
      performed under circulatory arrest with deep hypothermia. Additionally mitral
      valve repair for degenerative disease with posterior, autologous pericardium
      mitral valve ring was performed.

PMID- 19399331
TI  - [Atypical antipsychotic induced weight gain and metabolic disorders].
AB  - The advent of new antipsychotic drugs has improved the treatment of schizophrenic
      patients as well as those suffering from other severe psychiatric disorders. Its
      widespread use, however, has been associated to the development of obesity and
      metabolic disturbances such as diabetes mellitus, dyslipidemia and increased
      coronary risk. This has caused a serious concern, due to the high cardiovascular
      mortality that prematurely affects these patients. The etiology of these
      abnormalities is still a matter of debate, although it is generally believed that
      the new antipsychotic drugs have a control stimulating effect on appetite, and
      their use is associated to an increased level of cortisol and to an insulin
      resistance state. In addition, there is an increase in inflammatory mediator and
      cytokine production, induced by the pathophysiology of the schizophrenic process
      itself and also caused by the direct action of the antipsychotic drugs. In spite
      of the mounting evidence, the metabolic management of these patients is still
      deficient. A close follow-up in the initial stages of the antipsychotic treatment
      is recommended, as well as giving advice about diet and physical exercise.
      Finally, when obesity or other conditions associated to metabolic syndrome
      appear, the recommendation is to switch to drugs with less secondary effects or
      to add adjuvant medications to improve the overall evolution of these patients.

PMID- 19399332
TI  - [General aspects of homeopathy].
AB  - Homeopathic medicine is a type of therapy that appeared in Europe at the end of
      the eighteenth century. At the present time, it is widely accepted in developed
      countries as a form of alternative medicine. In Chile, health regulation includes
      homeopathy as pharmaceutical products and homeopathy is also considered a form of
      complementary medicine, that is well accepted by the public. The scientific
      rationale of homeopathy is based on an empiric type of thought that goes from the
      general to the particular. The symptoms that are valued are those that are
      particular to each sick individual. It uses diluted solutions of plants,
      minerals, animals and even venoms. There are basically two hypotheses to explain
      its mechanisms of action: The "immunological memory" and the "memory of water" or
      the transmission of electromagnetic information of the water. There still is
      needed to perform new studies to scientifically assess homeopathy and its
      usefulness, as an accepted alternative therapy.

PMID- 19399333
TI  - [Create or copy... Which is the difference?].
AB  - Creating and copying are two different processes; we must not confuse creativity
      with plagiarism. However, this distinction is problematic, because there is no
      possibility of creating from scratch, this implies that any creative act
      necessarily arises from accumulative experience, inevitably producing a
      continuity between old and new. Even so it is necessary to establish clearly the
      difference between creating and copying. It is not desirable that a matter of
      such importance remains in the nebula or that the relationship between creativity
      and ethics is kept unaware. There are many cases of plagiarism, but this cannot
      be a consolation. There is no gain when the existence of a plagiarism is ignored
      or concealed and less when it is unjustified.

PMID- 19399336
TI  - [Liaison psychiatry: referrals in a University Clinic in Colombia].

PMID- 19399335
TI  - [Liver transplantation in pediatric candidates].

PMID- 19399337
TI  - Microtubule proteins and their post-translational forms in the cerebrospinal
      fluid of patients with paraparesis associated with HTLV-I infection and in SH
      SY5Y cells: an in vitro model of HTLV-I-induced disease.
AB  - HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is
      characterized by axonal degeneration of the corticospinal tracts. The specific
      requirements for transport of proteins and organelles to the distal part of the
      long axon are crucial in the corticospinal tracts. Microtubule dysfunction could
      be involved in this disease, configuring an axonal transport disease. We measured
      tubulin and its post-translational modified forms (acetylated and tyrosinated) in
      CSF of patients and controls, as well as tau and its phosphorylated forms. There
      were no significant differences in the contents of tubulin and acetyl-tubulin
      between patients and controls; tyrosyl-tubulin was not detected. In HAM/TSP, tau
      levels were significantly reduced, while the ratio of pT181/total tau was higher
      in patients than in controls, this being completely different from what is
      reported in other neurodegenerative diseases. Phosphorylation at T181 was also
      confirmed by Mass Spectrometry analysis. Western Blotting with monospecific
      polyclonal antibodies against pS199, pT205, pT231, pS262, pS356, pS396, pS404 and
      pS422 did not show differences in phosphorylation in these residues between
      patients and controls. Treating human SH-SY5Y neuroblastoma cells, a well-known
      in vitro neurite retraction model, with culture supernatant of MT-2 cells (HTLV-I
      infected cell line that secretes the viral Tax protein) we observed neurite
      retraction and an increase in tau phosphorylation at T181. A disruption of normal
      phosphorylation of tau protein in T181 could result in its dysfunction,
      contributing to axonal damage.

PMID- 19399338
TI  - Misclassification probability as obese or lean in hypercaloric and normocaloric
      diet.
AB  - The aim of the present study was to determine the classification error
      probabilities, as lean or obese, in hypercaloric diet-induced obesity, which
      depends on the variable used to characterize animal obesity. In addition, the
      misclassification probabilities in animals submitted to normocaloric diet were
      also evaluated. Male Wistar rats were randomly distributed into two groups:
      normal diet (ND; n=31; 3.5 Kcal/g) and hypercaloric diet (HD; n=31; 4.6 Kcal/g).
      The ND group received commercial Labina rat feed and HD animals a cycle of five
      hypercaloric diets for a 14-week period. The variables analysed were body weight,
      body composition, body weight to length ratio, Lee Index, body mass Index and
      misclassification probability. A 5% significance level was used. The hypercaloric
      pellet-diet cycle promoted increase of body weight, carcass fat, body weight to
      length ratio and Lee Index. The total misclassification probabilities ranged from
      19.21% to 40.91%. In conclusion, the results of this experiment show that
      misclassification probabilities occur when dietary manipulation is used to
      promote obesity in animals. This misjudgement ranges from 19.49% to 40.52% in
      hypercaloric diet and 18.94% to 41.30% in normocaloric diet.

PMID- 19399339
TI  - Hematopoietic potential of mouse placenta with the application of placenta
      flushing.
AB  - Several major vascular tissues, such as the aorta-gonad-mesonephros region (AGM),
      yolk sac, and fetal liver have been confirmed to possess hematopoietic function.
      Recently, the placenta has been demonstrated as another hematopoietic organ.
      However, it is not conclusive whether the placenta possesses hematopoietic
      ability. Therefore, we undertook a series of experiments to study the
      hematopoietic functions of placenta. Fetal blood circulation in the placenta is
      difficult to be eliminated and its interference in the study of placental
      hematopoiesis is inevitable. With the application of placental flushing, fetal
      blood contained in the placenta was eliminated. We then made the further study of
      placental hematopoiesis after the E12.5 placenta was flushed. Our studies showed
      that placental cells expressing Sca-1, CD117 and CD34 were mainly restricted to
      the embryonic vessels of E12.5 placenta. The results of fluorescence activated
      cell sorter (FACs) analysis and colony forming cells (CFC) assay demonstrated
      that both placenta and placental blood contained hematopoietic stem/progenitor
      cells (HS/PCs), including CFU-GMs, CFU-GEMMs, BFU-Es, and HPP-CFCs. The frequency
      of HS/PCs in the placenta was 2-3 times that of placental blood. Therefore, it is
      necessary to clear placental blood out of the placenta in the studies of the
      hematopoietic potential of placenta. The placenta still possessed the
      hematopoietic potential after the fetal blood is flushed out. These observations
      provide further evidences that the placenta is a hematopoietic organ, as has been
      proposed for other embryonic hematopoietic sites.

PMID- 19399340
TI  - Methodological considerations related to sleep paradigm using event related
      potentials.
AB  - In the last few decades, several works on event related potentials (ERPs
      hereafter) during sleep have been reported. In spite of numerous studies, clear
      methodological rules for this kind of study are often missing, making it
      difficult to valorize the scope of these results. We propose here a description
      of methodological aspects to be considered when evaluating ERPs during sleep. The
      use of Rechtschaffen and Kales rules versus automatic methods is assessed, plus
      the additional use of certain quantitative measures. Additionally, two topics are
      discussed which must be controlled in ERPs sleep studies: the First Night Effect,
      and sleep disturbances. Better control of experimental paradigms is relevant for
      the growth of the neuroscience of sleep.

PMID- 19399341
TI  - Biocidal activity of partially purified fractions from methanolic extract of
      Garcinia kola (Heckel) seeds on bacterial isolates.
AB  - The in vitro antibacterial activity of crude methanolic extract of the seeds of
      Garcinia kola was investigated. The extracts exhibited antibacterial activities
      with zones of inhibition ranging from 10 mm to 25 mm. The minimum inhibitory
      concentration of the diethyl ether fraction was between 0.313 and 5.0 mg/ml,
      while that of butanol fraction varied from 0.157 to 5.0 mg/ml. The butanol
      fraction killed about 77% of Bacillus anthracis and 79% of Escherichia coli cells
      within 120 min at a concentration of 5.0 mg/ml. Protein leakage from the B.
      anthracis and E. coli cells when exposed to the butanol and diethyl ether
      fractions was observed. We conclude that Garcinia kola seed extract has a broad
      spectrum antibacterial activity, with the butanol and diethyl ether fractions
      being bactericidal as exemplified by the killing rate and protein leakage
      regimes, which suggest cell membrane disruption as a mechanism of action of the
      extract.

PMID- 19399342
TI  - Daucus carota as a novel model to evaluate the effect of light on carotenogenic
      gene expression.
AB  - Carotenoids are synthesized in prokaryotic and eukaryotic organisms. In plants
      and algae, these lipophilic molecules possess antioxidant properties acting as
      reactive oxygen species scavengers and exert functional roles in hormone
      synthesis, photosynthesis, photomorphogenesis and in photoprotection. During the
      past decade almost all carotenogenic genes have been identified as a result of
      molecular, genetic and biochemical approaches utilizing Arabidopsis thaliana as
      the model system. Studies carried out in leaves and fruits of A. thaliana and
      tomato determined that light regulates carotenoid biosynthesis preferentially
      through the modulation of carotenogenic gene transcription. In this work we
      showed for the first time that light induces accumulation of psy1, pds and zds2
      transcripts in leaves of Daucus carota (carrot), a novel plant model. In
      addition, modified roots of carrots exposed to light accumulate zds1, whereas the
      pds gene is highly repressed, suggesting that some carotenogenic genes, which are
      expressed in roots, are regulated by light. Additionally, light negatively
      regulates the development of the modified carrot root in a reversible manner.
      Therefore, this suggests that light affects normal growth and carotenogenic gene
      expression in the modified root of carrot plants. The molecular insight gained
      into the light-regulated expression of carotenoid genes in this and other model
      systems will facilitate our understanding of the regulation of carotenoid
      biosynthesis to improve the prospects for the metabolic engineering of carotenoid
      production in plants.

PMID- 19399343
TI  - DNA methylation profile in diffuse type gastric cancer: evidence for
      hypermethylation of the BRCA1 promoter region in early-onset gastric
      carcinogenesis.
AB  - Diffuse type gastric carcinoma is the most aggressive type of gastric cancer.
      This type of tumor is not preceded by precancerous changes and is associated with
      early-onset and hereditary syndromes. To test the hypothesis that DNA methylation
      profile would be useful for molecular classification of the diffuse type gastric
      carcinoma, DNA methylation patterns of the CpG Island of 17 genes were studied in
      104 cases and 47 normal adjacent gastric mucosa by Methylation-specific PCR,
      Immunohistochemistry and Hierarchical clustering analysis. The most frequent
      methylated genes were FHIT, E-cadherin, BRCA1 and APC (>50%), followed by p14,
      p16, p15, p73, MGMT and SEMA3B (20-49%). Hierarchical clustering analysis reveals
      four groups with different clinical features. The first was characterized by
      hypermethylation of BRCA1 and younger age (<45 years old), and the second by
      hypermethylation of p14 and p16 genes, male predominance and Epstein-Barr virus
      infection. The third group was characterized by hypermethylation of FHIT and
      antrum located tumors and the fourth was not associated with any clinical
      variables. In normal adjacent mucosa only the p73 gene was significantly less
      methylated in comparison to tumor mucosa. DNA methylation identified subgroups of
      diffuse type gastric cancer. Hypermethylation of BRCA1 associated with young age
      suggests a role in early-onset gastric carcinoma.

PMID- 19399344
TI  - Ethanol intake during lactation alters milk nutrient composition and growth and
      mineral status of rat pups.
AB  - Lactating Wistar rats were fed a liquid diet containing either ethanol [ethanol
      fed group (EFG)] or an isocaloric amount of carbohydrate [pair-fed group (PFG)]
      from day 1 postpartum up to day 14 of lactation, to investigate
      micro/macronutrient milk composition and the mineral status of pups. EFG
      presented a reduction of daily milk production and milk composition was
      significantly higher in protein and lower in carbohydrate, while the lipid
      content was similar to that of PFG. When compared to PFG, the milk of EFG had a
      decreased proportion of C22:6 n-3 fatty acid and an increase in medium-chain
      fatty acids and of several minerals. Pups of EFG showed reduced growth and a
      lower concentration of Cu and Sr in plasma and lower concentrations of Ca, P and
      Cl, and higher concentrations of Cd in the brain. We conclude that maternal EtOH
      intake greatly impairs lactational performance and modifies the mineral status of
      pups.

PMID- 19399345
TI  - Positive effects of green tea on hepatic dysfunction, lipid peroxidation and
      antioxidant defence depletion induced by cadmium.
AB  - Cadmium (Cd) is a highly toxic environmental and industrial cumulative pollutant
      that affects many organs, especially the liver. The present study was designed to
      evaluate the antioxidant effect of green tea on cadmium-induced hepatic
      dysfunction and oxidative stress in rats. Adult male Wistar rats were
      administered cadmium by injection of 20 micromoles/kg bw/every 3 days for six
      months. This study revealed significant (p < 0.05) liver dysfunction, lipid
      peroxidation and a decline in antioxidant enzyme activities in the liver of
      cadmium-treated rats compared to control animals. Compared to control rats, the
      activities of lactate dehydrogenase (LDH), gammaglutamyl transferase (GGT), acid
      phosphatase (PAC), phosphatase alkaline (PAL), as well as bilirubin and
      thiobarbituric acid-reactive substances (TBARs), were significantly (p < 0.05)
      increased in Cd-treated rats. Moreover, antioxidant enzyme activities, such as
      superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase, were
      significantly (p < 0.05) decreased in the liver of cadmium-treated rats. The oral
      administration of 5% aqueous green tea extract, along with cadmium treatment for
      six months, caused a significant (p < 0.05) improvement in cadmium-induced
      toxicity by significantly decreasing (p < 0.05) the activities of enzymatic
      markers of liver dysfunction (LDH, GGT, PAC, PAL activities, as well as the
      bilirubin rate). Indeed, green tea extract significantly increased (p < 0.05)
      antioxidant enzymatic activities (SOD, Catalase, GPX) in rat liver, compared to
      those given cadmium alone. Thus, the oral administration of green tea, along with
      cadmium significantly (p < 0.05) improves cadmium-induced liver dysfunction and
      stress oxidant in rats' liver.

PMID- 19399346
TI  - Chlorpheniramine impairs spatial choice learning in telencephalon-ablated fish.
AB  - This work investigated the effect of the H1 receptor blockade in the forebrain of
      ablated Carassius auratus in a simple stimulus-response learning task using a T
      maze test with positive reinforcement. The goldfish were submitted to surgery for
      removal of both telencephalic lobes five days before beginning the experiment. A
      T-shaped glass aquarium was employed, with two feeders located at the extremities
      of the long arm. One of the two feeders was blocked. The experimental trials were
      performed in nine consecutive days. Each fish was individually placed in the
      short arm and confined there for thirty seconds, then it was allowed to swim
      through the aquarium to search for food for ten minutes (maximum period). Time to
      find food was analysed in seconds. Animals were injected intraperitoneally with
      chlorpheniramine (CPA) at 16 mg/kg of body weight or saline after every trial,
      ten minutes after being placed back in the home aquarium. The results show that
      all the training latencies of the A-SAL group were higher than the latencies of
      the S-SAL group. The S-SAL group had decreased latencies from the second trial
      on, while the S-CPA group showed decreased latencies after the fourth trial. The
      A-SAL group showed reduced latencies after the fifth trial, but the A-CPA group
      maintained the latencies throughout the experiment. This suggests that CPA
      impairs the consolidation of learning both on telencephalon ablated animals and
      in sham-operated ones through its action on mesencephalic structures of the brain
      and/or on the cerebellum in teleost fish.

PMID- 19399347
TI  - Gluconate as suitable potential reduction supplier in Corynebacterium glutamicum:
      cloning and expression of gntP and gntK in Escherichia coli.
AB  - Corynebacterium glutamicum is widely used in the industrial production of amino
      acids. We have found that this bacterium grows exponentially on a mineral medium
      supplemented with gluconate. Gluconate permease and Gluconokinase are expressed
      in an inducible form and, 6-phosphogluconate dehydrogenase, although
      constitutively expressed, shows a 3-fold higher specific level in gluconate grown
      cells than those grown in fructose under similar conditions. Interestingly, these
      activities are lower than those detected in the strain Escherichia coli M1-8,
      cultivated under similar conditions. Additionally, here we also confirmed that
      this bacterium lacks 6-phosphogluconate dehydratase activity. Thus, gluconate
      must be metabolized through the pentose phosphate pathway. Genes encoding
      gluconate transport and its phosphorylation were cloned from C. glutamicum, and
      expressed in suitable E. coli mutants. Sequence analysis revealed that the amino
      acid sequences obtained from these genes, denoted as gntP and gntK, were similar
      to those found in other bacteria. Analysis of both genes by RT-PCR suggested
      constitutive expression, in disagreement with the inducible character of their
      corresponding activities. The results suggest that gluconate might be a suitable
      source of reduction potential for improving the efficiency in cultures engaged in
      amino acids production. This is the first time that gluconate specific enzymatic
      activities are reported in C. glutamicum.

PMID- 19399350
TI  - Work characteristics as predictors of physiological recovery on weekends.
AB  - OBJECTIVES: This study investigated whether work characteristics predict
      physiological recovery on a rest day. Specifically, we aimed to show that high
      demands and low control at work would lead to higher cortisol values and thus
      poor recovery on a rest day. METHODS: A total of 69 individuals participated in
      this study. In addition to analyzing questionnaire responses, we measured
      salivary cortisol on two workdays and on a subsequent rest day (a Sunday). We
      used multiple regression analysis. We controlled for the workday cortisol level;
      results reflect the relative change in cortisol from workday to rest day. In
      addition, we controlled for gender, since this relates to cortisol levels at
      work. RESULTS: We found that control at the workplace predicted cortisol levels
      on a rest day. Specifically, individuals with less job control had higher
      cortisol levels, and consequently poorer recovery on the rest day than those with
      more control. Neither job demands nor the interaction of demands and control
      predicted a change in cortisol levels from workday to rest day. CONCLUSIONS: The
      results indicated that a lack of control at work impairs physiological recovery
      on the weekend, one of the central recuperation periods. In light of the
      potential importance of incomplete recovery with respect to long-term ill health,
      it should be considered crucial to ensure job control at the workplace.

PMID- 19399352
TI  - Adult rats exposed to low-doses of di-n-butyl phthalate during gestation exhibit
      decreased grooming behavior.
AB  - Developmental neurotoxicity of low-dose di-n-butyl phthalate (DBP) to rats was
      studied. Pregnant rats were orally given DBP at doses less than 1.0 mg/kg/day
      during gestation period. The body weight of all dams and their offspring as well
      as the offspring's motor function showed no significant adverse effect. At 21
      weeks, behaviors of male rats were examined by placing into a test cage. The rats
      born from dams exposed to 10 microg DBP/kg/day exhibited a significant decrease
      of grooming. This indicates low-dose DBP adversely affects emotional stability in
      a novel environment.

PMID- 19399351
TI  - Determinants of mental well-being in medical students.
AB  - INTRODUCTION: Mental disorders constitute an increasingly important public health
      problem in the general population. Therefore, investigation of the determinants
      and state of mental health of those who will be treating patients, that is,
      future medical doctors, is justified. The paper gives an account of a mental
      health survey of medical students at a university in Hungary. METHODS: A
      representative sample of year I-V students (N = 100) filled an anonymous
      standardized self-administered questionnaire that included demographic and
      socioeconomic items, mental well-being characterized by a sense of coherence
      (SOC) and psychological distress, as well as health behaviour. SOC was measured
      by the 13-item Antonovsky questionnaire and psychological distress was measured
      by the 12-item general health questionnaire (GHQ). Models for estimating mental
      well-being in relation to various determinants were built by backward stepwise
      regression. RESULTS: Almost one-fifth of the students scored above the strict
      threshold on the GHQ indicating notable psychological distress. SOC showed
      significant positive correlation with perceived health and significant negative
      correlation with psychological distress. SOC and psychological distress were
      determined by different sets of explanatory variables in the regression models.
      Psychological distress and the use of sedative without medical prescription are
      inversely related to SOC; whereas social support and female gender show positive
      correlation to SOC according to our estimation. SOC, as expected, was a strong
      explanatory variable for psychological distress, forecasting an improvement in
      the GHQ score. CONCLUSION: Psychological distress was significantly greater in
      our sample of Hungarian medical students than in the same age group of the
      general population. Psychological distress is strongly related to SOC and can be
      estimated by our proposed models. Both SOC and psychological distress can be used
      to characterize the mental health of future medical doctors, the improvement of
      which needs attention even during their training.

PMID- 19399353
TI  - Etiology of post-uterosacral suspension neuropathies.
AB  - INTRODUCTION AND HYPOTHESIS: The goal of our investigation was to find a
      neurological explanation for neuropathies reported following some uterosacral
      ligament suspension (USLS) [2-3]. METHODS: We dissected the neural structures
      beneath the USL in seven female, adult, embalmed cadavers. We made a literature
      review to determine the spinal nerve sensory fiber composition of each exposed
      neural structure and the dermatome(s) that it innervates. We then compared
      anticipated sensory neuropathies for each neural structure with neuropathies
      following USLS to determine which neural structure entrapment could explain the
      reported symptoms. RESULTS: Several neural structures located beneath the
      uterosacral ligament (USL) are vulnerable to suture entrapment during USLS.
      Anticipated clinical outcomes of entrapments are discussed. CONCLUSIONS:
      Entrapment of S2 sensory fibers in the second trunk of the sacral plexus or in
      the intrapelvic portion of the sciatic nerve is the most plausible etiology for
      reported neuropathies following USLS.

PMID- 19399354
TI  - Minimizing the risk of childbirth-induced pelvic floor dysfunctions in the
      developing world: "preventive" urogynecology.

PMID- 19399355
TI  - Does avulsion of the puborectalis muscle affect bladder function?
AB  - INTRODUCTION AND HYPOTHESIS: The levator ani muscle is generally thought to play
      a role in urinary continence, with incontinence assumed to be due to abnormal
      muscle function or morphology. This study examined whether avulsion of the
      puborectalis muscle is associated with symptoms or signs of bladder dysfunction.
      METHODS: In a retrospective observational study, we reviewed the records of 425
      women who had attended a urogynecological unit for independent flowmetry,
      multichannel urodynamic testing, and 4D pelvic floor ultrasound. RESULTS: Mean
      age was 55 years (range, 17-87 years). Of 420 women with complete datasets, 104
      (25%) were diagnosed with a puborectalis muscle avulsion. These women were less
      likely to suffer from stress urinary incontinence (SUI; P < 0.001) and urodynamic
      stress incontinence (USI; P = 0.065) and more likely to present with symptoms of
      prolapse (P < 0.001) and show signs of voiding dysfunction (P = 0.005). The
      negative association between avulsion and SUI persisted in multivariate models.
      CONCLUSION: Puborectalis muscle trauma is not associated with an increased risk
      of SUI or USI in a urogynecological population, even when controlling for
      symptoms or signs of prolapse and previous surgery.

PMID- 19399356
TI  - Effect of low-level laser therapy on the fracture healing process.
AB  - Low-level laser therapy (LLLT) is a biophysical form of intervention in the
      fracture-repair process, which, through several mechanisms, accelerates the
      healing of fractures and enhances callus formation. The effect of laser on
      fracture healing is controversial. Some authors affirm that LLLT can accelerate
      bone formation by increasing osteoblastic activity. The objective of our study
      was to evaluate the effect of laser therapy on fracture healing. Thirty rabbits
      were subjected to tibial bone open osteotomies that were stabilized with external
      fixators. The animals were divided into two study groups: laser group and control
      group. Callus development and bone mineral density were quantitatively evaluated
      by CT; the animals were then killed and the fractures were assessed for
      biomechanical properties. The results demonstrated that the increasing rate of
      bone mineral density was higher in the laser (L) group than in the control (C)
      group. CT at 5 weeks revealed a mean callus density of 297 Hounsfield units (HU)
      for the control group and 691 HU for the L group, which was statistically
      significant (P = 0.001). In the L group, the mean recorded fracture tension was
      190.5 N and 359.3 N for healed and intact bones, respectively, which was
      statistically significant (P < 0.001). The result of the study showed that the
      use of laser could enhance callus development in the early stage of the healing
      process, with doubtful improvement in biomechanical properties of the healing
      bone; therefore, laser therapy may be recommended as an additional treatment in
      non-union fractures in humans.

PMID- 19399357
TI  - Metabolic syndrome: a follow-up study of acute depressive inpatients.
AB  - Previous studies pointed out the high prevalence of the metabolic syndrome among
      patients with bipolar disorder and major depression. A link between depression
      and a metabolic syndrome remains in dispute despite these studies. This study was
      conducted to evaluate the occurrence of the metabolic syndrome in depressive
      inpatients, to analyze the association between the severity of depression and the
      metabolic syndrome and to screen specific laboratory values in the course of
      depressive illness. 60 acute depressive patients were recruited for the study and
      underwent psychometric testing [21-item Hamilton Depression Rating Scale (HAMD),
      Beck Depression Inventory (BDI), Clinical Global Impression Scale (CGI) and
      Global Assessment of Functioning Scale (GAF)] and a metabolic syndrome screening
      using the modified criteria of the American National Cholesterol Education
      Program (NCEP) Treatment Panel III (ATP III). Moreover, CRP, cholesterol, HDL
      cholesterol, fasting glucose, triglyceride and leptin levels were measured. 42
      patients were reexamined in state of (partial) remission. Depression was
      reassessed using the 21-item HAMD, and laboratory values were analyzed a second
      time. 25% of the depressive patients fulfilled the criteria of metabolic syndrome
      (MS+). Only in the MS+ group, a positive correlation between triglyceride blood
      levels and severity of depression became evident as well in the state of acute
      depression as in the state of remission. In the group of patients without
      metabolic syndrome, laboratory values were not associated with severity of
      depression. An association between metabolic parameters and the course of
      depression could only be detected in the group of patients with metabolic
      syndrome. These findings suggest that, in these patients, a beneficial outcome of
      depressive illness may improve the metabolic situation.

PMID- 19399358
TI  - Heritability of Trail Making Test performance in multiplex schizophrenia
      families: implications for the search for an endophenotype.
AB  - The impairment of the Trail Making Test (TMT) performance as a measure of
      executive function deficits has been found both in patients with schizophrenia
      and in their unaffected first-degree relatives, suggesting that it might be
      considered as a familial vulnerability marker, but its heritability estimates are
      not well known. This study investigated the genetic heritability of impairments
      in TMT performance using a sample of 80 schizophrenia patients, 145 unaffected
      first-degree relatives and 127 healthy controls from families with multiple
      members with schizophrenia. Consistent with previous reports in the literature,
      relatives performed in between healthy controls and schizophrenia patients. Based
      on these results, a variance component-analysis provided small, but significant
      additive heritability estimates for performance indices relating performance in
      TMT-version A to TMT-version B. These results showed that this significant but
      small evidence of heritability on the one hand suggests an association with
      genetic predisposition to schizophrenia, but that TMT performance is also
      associated with epigenetic or environmental factors.

PMID- 19399359
TI  - Incidence, clinical presentation and pathological features of benign sclerosing
      cholangitis of unknown origin masquerading as biliary carcinoma.
AB  - BACKGROUND: Benign obstructions of the liver hilum are occasionally encountered
      in surgically resected cases. Some of these cases are pathologically classified
      as benign sclerosing cholangitis and are not clearly categorized. This study aims
      to elucidate the clinicopathological features of benign sclerosing cholangitis of
      unknown origin. METHODS: Patients who had undergone surgery of the proximal bile
      duct from 1993 to 2008 on suspicion of proximal bile carcinoma were evaluated,
      then their clinical presentation, histopathological and immunohistochemical
      findings were retrospectively analyzed. RESULTS: One hundred seventy-six patients
      underwent surgery during this period. Of these, five patients were diagnosed with
      benign sclerosing cholangitis of unknown origin. All five patients were middle
      aged with no history of autoimmune disease. One patient died of recurrent
      cholangitis after surgery. Histopathologically, lymphoplasmacytic infiltrations
      were observed in all five cases. Among them, the clinicopathological findings of
      one patient were compatible with IgG4-related sclerosing cholangitis, and the
      other two patients had unusual histopathological findings with prominent lymph
      follicular formation. CONCLUSIONS: Although patients with benign sclerosing
      cholangitis of unknown origin comprise a heterogeneous population, they can be
      further classified into subgroups. The response to immunosuppressive therapy,
      long-term prognosis and histological morphology of the disease should be
      considered in order to classify these cases of sclerosing cholangitis.

PMID- 19399361
TI  - Treatment of pancreatic fistula after pancreatoduodenectomy using a hand-made T
      tube.
AB  - BACKGROUND/PURPOSE: To describe a technique for the treatment of postoperative
      pancreatic fistula (POPF) after pancreatoduodenectomy (PD) using a hand-made T
      tube. METHODS: Reconstruction after PD was performed by a modified Child's
      method. A 3-mm tube and a 2-mm tube were connected in a 'T' shape. This hand-made
      T-tube was inserted into both the pancreatic duct and the jejunal limb, using two
      guidewires through a sinus tract of POPF. After a few days, the external end of
      the T-tube was closed with a metallic tip, and the internal pancreatic drainage
      was completed. RESULTS: The indication criteria for the T-tube treatment are as
      follows: (1) the pancreatic drainage tube inserted during operation has been
      dislodged; and (2) either the main pancreatic duct or the jejunal limb can be
      demonstrated on fistulograms. In the 30 years between 1978 and 2007, 642 patients
      underwent PD (pylorus-preserving, n = 210; Whipple, n = 302; and
      hepatopancreatoduodenectomy, n = 130). The T-tube treatment was performed in 9
      patients (pylorus-preserving, n = 5; Whipple, n = 1; and
      hepatopancreatoduodenectomy, n = 3). The median duration between surgery and the
      T-tube placement was 64 days (range, 22-107 days). The median hospital stay after
      the T-tube placement was 12 days (range, 7-54 days). Neither major nor minor
      complications associated with the T-tube treatment occurred. The T-tube was
      removed in 5 patients after a median of 2 months (range, 2-24 months). Of these
      patients, 4 are alive without recurrence of carcinoma, and 1 patient died of
      recurrence 56 months after surgery. The other 4 patients died of recurrence
      before removal of the T-tube, at 11 months after placement of the tube (range, 7
      15 months) without any complications associated with the T-tube treatment.
      CONCLUSIONS: T-tube treatment is a minimally invasive, simple, safe, and reliable
      technique that can dramatically improve grade C POPF. This procedure should be
      considered as a first-line treatment of choice in selected patients with
      refractory grade C POPF.

PMID- 19399360
TI  - A comparative study of pathological staging systems in predicting recurrent
      hepatocellular carcinoma after liver transplantation.
AB  - BACKGROUND/PURPOSE: The applicability of the staging systems of hepatocellular
      carcinoma (HCC) to liver transplantation (LT) has not been fully evaluated.
      Therefore, we compared the HCC recurrence after LT as predicted by various
      staging systems, including the American Joint Committee on Cancer (AJCC) system
      5th edition, the AJCC system 6th edition, the American Liver Tumor Study Group
      (ALTSG) system, and the Liver Cancer Study Group of Japan (LCSGJ) system.
      METHODS: A total of 108 patients who had HCC were classified according to these
      systems. We compared cumulative recurrence curves, recurrence-free survival
      curves, and overall survival curves of the systems estimated by Kaplan-Meier
      method. We compared cumulative event rates among different stages with the log
      rank test for each staging system. RESULTS: The log-rank test showed that the
      cumulative recurrence rates were different among different stages with a
      statistical significance for the staging systems except for the AJCC 5th edition
      system. Cumulative recurrence curves by the AJCC 6th edition system and the LCSGJ
      system showed better visual separation than the other two systems. With respect
      to recurrence-free survival and overall survival, no staging systems showed
      significant discriminative power. CONCLUSIONS: The current AJCC tumor-node
      metastasis staging and the LCSGJ system are superior in predicting HCC recurrence
      after LT.

PMID- 19399362
TI  - Transjugular extension of meningioma into the mediastinum-a case report.
AB  - A case of a tentorial meningioma with atypical histological features invading the
      transverse sinus and extending along the internal jugular vein up to the superior
      mediastinum is described. This report illustrates one of the many ways
      meningiomas spread beyond the cranial cavity and the difficulty in managing such
      a problem.

PMID- 19399363
TI  - Pseudomeningeal syndrome of Dupre associated with cervical discopathy--case
      report.
AB  - BACKGROUND AND PURPOSE: The below publication presents a case of a 51-year-old
      patient with cervical discopathy of unusual clinical course. CASE REPORT: The
      symptoms of the disease suddenly became aggravated and took a form of meningeal
      syndrome without inflammation of cerebrospinal fluid. The authors emphasize the
      symptomatology and diagnostic difficulties connected to unusual clinical course
      of cervical discopathy at the level of VC3/VC4. DISCUSSION: Both medical and
      neurosurgical approaches to clinical history of cervical discopathic patient were
      presented in details. The patient underwent anterior cervical interbody fusion
      and the operative procedure was very effective for a few years up till now.

PMID- 19399364
TI  - Iatrogenic tension pneumothorax resulting in pneumocephalus after insertion of a
      ventriculoperitoneal shunt: an unusual complication.
AB  - We report the case of an iatrogenic tension pneumothorax related to the placement
      of a ventriculoperitoneal shunt, followed by pneumocephalus. The patient was
      pending cranioplasty and shunt placement after decompressive craniectomy for
      acute subdural hematoma and posttraumatic hydrocephalus. Facilitating the severe
      and potential life-threatening complication was a severe obesity of the patient
      as well as incorrect surgical technique.

PMID- 19399365
TI  - Gliosarcoma with osteosarcomatous features: a short illustrated review.
AB  - INTRODUCTION: Gliosarcoma is a rare, malignant, biphasic brain tumor formed by
      both glioblastoma and sarcomatous components. Various lines of differentiation
      are described in the latter component, but most commonly fibrosarcomatous and
      pleomorphic sarcoma are present. Osteosarcomatous features are exceedingly rare.
      OBJECTIVE: We report a case of gliosarcoma with osteosarcomatous features in a 33
      year-old woman. METHODS: Histologically, the sarcomatous portion displayed a
      typical pattern of fibrosarcoma associated with areas of osteoid formation.
      RESULTS AND CONCLUSION: Immunohistochemical glial fibrillary acid protein (GFAP)
      expression was seen only in the glioblastoma portion. Clinicopathological
      characteristics and radiological data of this rare condition were reviewed.
      Possible differential diagnoses and potential histogenesis were also discussed.

PMID- 19399366
TI  - Combined trans-sphenoidal and simultaneous trans-ventricular-endoscopic
      decompression of a giant pituitary adenoma: case report.
AB  - OBJECTIVE: This is the first report of the simultaneous combined use of trans
      sphenoidal and trans-ventricular-endoscopic route for decompression of a giant
      pituitary adenoma. METHOD: A 38 year old man presented to us with symptoms of
      raised intracranial pressure along with visual and hypothalamic disturbances. The
      CT scan revealed destruction of the sella by a large (5 x 3.5 x 2.5 cm) well
      defined enhancing mass in the sella and suprasellar region extending laterally up
      to the cavernous sinuses and both carotid arteries and superiorly into the lumen
      of the 3rd ventricle producing obstructive hydrocephalus. On T2WI of the non
      contrast MRI scan the mass was iso-intense to grey matter suggesting the
      possibility of a firm nature of the adenoma. The tumour was first approached by
      the standard trans-sphenoidal route and as predicted from the pre-operative MRI,
      the tumour was found to be firm and not amenable to suction. After decompression
      of the intra-sellar part of the tumour, the intracranial pressure was raised in
      an attempt to make the remainder of the tumour descend into the sella but without
      success. The suprasellar part of the tumour was then simultaneously addressed via
      a trans-ventricular-endoscopic route but the firm tumour did not yield to
      endoscopic instruments viz. biopsy forceps, angiographic catheter and
      electrosurgical probes. It was then gently pushed down towards the sella and
      decompressed piecemeal by using trans-sphenoidal instruments. The sellar cavity
      was reconstructed using fat, fascia lata graft and a piece of septal bone.
      RESULTS: Post-operatively, the patient showed a remarkable improvement of his
      symptoms of raised intracranial pressure, hypothalamic dysfunction and visual
      disturbances. Follow-up imaging at 2 months and 1 year, did not show any residual
      or recurrent tumour. CONCLUSIONS: This novel technique of the combined trans
      sphenoidal and simultaneous trans-ventricular-endoscopic approach is a viable
      option for patients with giant fibrous pituitary adenoma when the tumour is not
      yielding to the trans-sphenoidal route alone.

PMID- 19399367
TI  - Techniques of reoperation for a giant regrown anterior communicating artery
      aneurysm harboring long-implanted clips and compacted coil mesh.
AB  - A 57-year-old woman presented with a progressive deterioration of vision. She had
      previously undergone clipping for a ruptured small anterior communicating artery
      (Acom) aneurysm 7 years prior to admission and additional coiling for recurrence
      2 years prior to admission. Angiography showed regrown out-pouching of the sac,
      which measured 27 x 18 mm. A decision was made to perform surgical treatment to
      alleviate the mass effect of the aneurysm. Unique techniques for revision of the
      scarred surgical corridor, removal of old clips, resection of the coiled mass,
      thrombectomy, and intra-aneurysmal endarterectomy were required to allow
      placement of the final clips. The patient recovered uneventfully, and her vision
      was satisfactorily restored.

PMID- 19399369
TI  - Stroke in cancer patients: a risk factor analysis.

PMID- 19399368
TI  - Differentiating attention-deficit/hyperactivity disorder inattentive and combined
      types: a (1)H-magnetic resonance spectroscopy study of fronto-striato-thalamic
      regions.
AB  - Despite the implication of fronto-striatal circuits in attention
      deficit/hyperactivity disorder (ADHD), there is a lack of information on the role
      of these regions, especially the thalamus, in the heterogeneity of ADHD. We
      assessed the (1)H-magnetic resonance spectroscopy profile in ventromedial
      prefrontal cortex (VMPFC)-thalamic-striatal regions bilaterally in three groups
      of subjects (age range 18-24 years old): ADHD inattentive type (ADHD-I; n = 9),
      ADHD combined type (ADHD-C; n = 10) and non-ADHD controls (n = 12). The peaks of
      N-acetylaspartate, Choline (Cho), myo-inositol (mI), creatine (Cr) and glutamate
      glutamine-GABA (Glx) to Cr were calculated. Subjects with ADHD-C showed lower
      mI/Cr ratio in the right VMPFC than controls, higher Cho/Cr ratio in the left
      thalamus-pulvinar than the ADHD-I group and higher Glx/Cr ratio in left putamen
      than individuals with ADHD-I and controls. This metabolic profile suggests a
      disruption of fronto-striato-thalamic structures in the ADHD-C as a result of
      lower neuronal energetic metabolism.

PMID- 19399370
TI  - M118, a novel low-molecular weight heparin with decreased polydispersity leads to
      enhanced anticoagulant activity and thrombotic occlusion in ApoE knockout mice.
AB  - Heparin and low-molecular weight heparin (LMWH) are complex, heterogeneous
      polysaccharides used in the treatment of arterial and venous thrombosis. M118 is
      a novel LMWH with low polydispersity and pronounced anti-Xa and anti-thrombin
      (IIa) activity as compared to current LMWHs. To determine if M118 is effective in
      preventing thrombosis in the setting of a vascular plaque, apolipoprotein E
      knockout mice fed a high fat diet were injected with M118, enoxaparin,
      unfractionated heparin, or saline control and examined for arterial thrombosis
      using a rose bengal laser induced carotid artery injury model. M118 significantly
      increased the time to occlusion as compared to control and unfractionated heparin
      but not compared to enoxaparin although fewer M118 treated animals had any
      vascular occlusion present at the time of protocol completion. Platelet
      neutrophil aggregates were studied by flow cytometry and were found to be
      decreased with M118 as compared to enoxaparin. This is the first published report
      examining M118, a novel LMWH designed to have low polydispersity and enhanced
      anticoagulant activity. In an animal model of vascular plaque, M118 is a potent
      inhibitor of arterial thrombosis and, despite lower in vivo anti-Xa and anti-IIa
      activity levels, M118 was superior to UFH in the prevention of arterial
      thrombosis.

PMID- 19399371
TI  - Optimized bacterial expression and purification of the c-Src catalytic domain for
      solution NMR studies.
AB  - Progression of a host of human cancers is associated with elevated levels of
      expression and catalytic activity of the Src family of tyrosine kinases (SFKs),
      making them key therapeutic targets. Even with the availability of multiple
      crystal structures of active and inactive forms of the SFK catalytic domain (CD),
      a complete understanding of its catalytic regulation is unavailable. Also
      unavailable are atomic or near-atomic resolution information about their
      interactions, often weak or transient, with regulating phosphatases and
      downstream targets. Solution NMR, the biophysical method best suited to tackle
      this problem, was previously hindered by difficulties in bacterial expression and
      purification of sufficient quantities of soluble, properly folded protein for
      economically viable labeling with NMR-active isotopes. Through a choice of
      optimal constructs, co-expression with chaperones and optimization of the
      purification protocol, we have achieved the ability to bacterially produce large
      quantities of the isotopically-labeled CD of c-Src, the prototypical SFK, and of
      its activating Tyr-phosphorylated form. All constructs produce excellent spectra
      allowing solution NMR studies of this family in an efficient manner.

PMID- 19399372
TI  - Glutarate and N-acetyl-L-glutamate buffers for cell-free synthesis of selectively
      15N-labelled proteins.
AB  - Cell-free protein synthesis provides rapid and economical access to selectively
      15N-labelled proteins, greatly facilitating the assignment of 15N-HSQC spectra.
      While the best yields are usually obtained with buffers containing high
      concentrations of potassium L-glutamate, preparation of selectively 15N-Glu
      labelled samples requires non-standard conditions. Among many compounds tested to
      replace the L-Glu buffer, potassium N-acetyl-L-glutamate and potassium glutarate
      were found to perform best, delivering high yields for all proteins tested, with
      preserved selectivity of 15N-Glu labelling. Assessment of amino-transferase
      activity by combinatorial 15N-labelling revealed that glutarate and N-acetyl-L
      glutamate suppress the transfer of the 15N-alpha-amino groups between amino acids
      less well than the conventional L-Glu buffer. On balance, the glutarate buffer
      appears most suitable for the preparation of samples containing 15N-L-Glu while
      the conventional L-Glu buffer is advantageous for all other samples.

PMID- 19399373
TI  - Dietary exposure to metals by individuals living near a hazardous waste
      incinerator in Catalonia, Spain: temporal trend.
AB  - The concentrations of arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr),
      mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn), thallium (Tl),
      and vanadium (V) were determined in a number of foodstuffs purchased during 2006
      in various localities of Tarragona County (Catalonia, Spain), near a hazardous
      waste incinerator, which has been operating since 1999. The dietary intake of the
      above elements by the population of the area was subsequently estimated. The
      results were compared with those obtained in previous surveys (baseline 1997 and
      2002) performed in the same area. The levels of Be, Tl, and V were under their
      respective limits of detection in all samples. The estimated dietary intakes of
      the elements analyzed in the current survey by an adult man of 70 kg were the
      following: 351 microg/day for As, 4.6 microg/day for Cd, 57.5 microg/day for Cr,
      7.1 microg/day for Hg, 2,229 microg/day for Mn, 78.0 microg/day for Ni, 39.9
      microg/day for Pb, and 37.9 microg/day for Sn. On average, fish and seafood were
      the main contributor to the total dietary intake of As, Cd, and Hg and one of the
      most important for Pb. In general terms, the differences on metal exposure
      through dietary intake between the present and our two previous surveys were not
      particularly relevant. The current intake of the most toxic elements (As, Cd, Hg,
      and Pb) remains under the respective Provisional Tolerable Weekly Intakes
      established by the Food and Agriculture Organization/World Health Organization.

PMID- 19399374
TI  - [Relevancy and binding character of standards for the safety of medical devices].
AB  - Medical devices are essential for diagnosis and therapy of diseases. To ensure
      that this large and heterogeneous product group is safe and fulfills the expected
      performance, there are national and international laws and directives which
      define essential requirements for medical devices. Since it is not possible on
      the level of a law to demand concrete specifications for completely different
      products which in addition are subject to technical improvement, there are
      references to the relevant standards in the legal regulations. When writing a
      technical standard, the experts of the particular standard committee incorporate
      the current state of technology. It is important to the standard committees that
      as many as possible of all groups who are interested in a specific subject
      actively participate in the development of the standard. Hence, standards
      guarantee safety for patients and user, while also supporting the manufacturer in
      fulfilling the various international requirements and regulations.

PMID- 19399375
TI  - [Methodical reflections on epidemiological methods to measure adverse medical
      device events].
AB  - Drugs and medical devices are common remedies in patient care. Concerning patient
      safety, much research has been undertaken to study medication-related events,
      such as adverse drug events or medication errors; however, only little is known
      about device-related events and patient safety. Until now, only one survey on the
      epidemiology of adverse medical device events has been published. Estimates
      amount to 8.4 adverse medical device events/100 hospitalizations. As this
      indicates, further research is needed on epidemiological methodology to
      investigate the frequency, distribution, causes and results of medical device
      related events. Only profound knowledge will constitute a resilient base for the
      development of safety strategies which can be then implemented and evaluated.
      Also in the German health care system, the special challenges described for data
      collection have to be mastered.

PMID- 19399376
TI  - [Evaluation of PET-CT : product safety, clinical usefulness, reimbursement in
      Germany and the USA].
AB  - Since 1994, PET - and later PET-CT - have gained significant clinical importance.
      Since 2002, PET-CT systems (PET + multislice CT) are available. The combination
      of high sensitivity PET images fused with high resolution CT images has gained
      widespread clinical acceptance for diagnosis, staging and re-staging as well as
      prediction of response to chemotherapy in oncology. Besides oncology, there are
      clear indications in diseases of the heart and the brain. The development of new
      systems in mainly based on multislice CT (64 slice). Radiopharmacology is
      advancing quickly, especially in the fields of oncology and neurological
      disorders. However, the limited reimbursement in Germany hampers this
      development.

PMID- 19399377
TI  - [Patient safety in medical technology research].
AB  - The message of this article is that patient safety must be an essential part of
      thinking and planning in research for medical technology. Which aspects must be
      considered already in an early phase of any project are presented. The most
      important standards are listed briefly. Then the topics technical safety and
      electromagnetic compatibility (EMC), clinical evaluation, risk analysis,
      biological evaluation of materials, ergonomics, the special aspects of medical
      devices that include pharmacological components, and the requirements of software
      packages and implemented algorithms are discussed.

PMID- 19399378
TI  - [Cutaneous marginal zone lymphoma (SALT) and infection with Borrelia
      burgdorferi].
AB  - A relationship between Borrelia burgdorferi and the development of cutaneous B
      cell lymphoma (CBCL) has been long discussed. B. burgdorferi DNA has been
      detected in patients with CBCL and a response of CBCL to antibiotics has been
      observed. In our patient with a Borrelia infection, a marginal zone lymphoma
      (SALT) regressed after ceftriaxone therapy. This further case of a combined
      appearance of CBCL and B. burgdorferi underlines a possible relationship as an
      example of an infectious trigger in tumorigenesis.

PMID- 19399379
TI  - [Suicidal ideation, anxiety and depression in adult patients with atopic
      dermatitis].
AB  - BACKGROUND: Atopic dermatitis is a chronic skin disease which is increasing in
      incidence and prevalence. An understanding of the mental burden patients carry is
      essential for successful psychodermatological treatment. PATIENTS AND METHODS: 62
      adult atopic dermatitis patients were tested with a questionnaire and compared
      with a matched group of 62 healthy persons. Using the questionnaire for assessing
      suicide risk of Poldinger, suicidal ideations were assessed. Anxiety and
      depression were detected by using HADS-D; the severity of symptoms by patients'
      self-evaluation based on SCORAD index. Finally, the onset of atopic dermatitis
      was established. RESULTS: A significantly higher level of suicidal ideation,
      anxiety and depression was shown among patients with atopic dermatitis. All three
      aspects showed a medium effect size. Strong correlations between severity of
      symptoms and psychological burden were observed. 16.1% of patients with atopic
      dermatitis suffered from suicidal ideation, while only 1.6% in control group did,
      producing an odds ratio of 11.73 (95%CI 1.45-94.71). CONCLUSION: Suicidal
      ideation, anxiety and depression are important factors, which should be addressed
      when treating atopic dermatitis.

PMID- 19399380
TI  - [Linear IgA disease with ocular involvement associated with ulcerative colitis].
AB  - The association of linear IgA disease (LAD), ulcerative colitis and scarring
      ocular involvement is very rare and represents a considerable therapeutic
      challenge. We report a 48-year-old male diagnosed with ulcerative colitis in
      1995, who received long-term methylprednisolone therapy. Later, he developed
      ocular inflammation with conjunctival scarring and synechiae formation as well as
      episodes of vesicles. Although azathioprine was added to his regimen, the disease
      was not controlled. After the diagnosis of LAD was established, dapsone was
      added. With this therapy, the ocular inflammation decreased significantly and the
      methylprednisolone dose could be successfully tapered slowly without reappearance
      of vesicles.

PMID- 19399381
TI  - Reducing the risk of stroke in type 2 diabetes: pathophysiological and
      therapeutic perspectives.
AB  - Reducing the excess cerebrovascular burden in patients with type 2 diabetes
      remains a major therapeutic challenge, especially with respect to the high risk
      of recurrent events. Targeting the traditional metabolic risk factors of
      hypertension, dyslipidemia, and hyperglycemia has failed to remove this excess
      risk, and agents targeting thrombotic risk (i.e., antiplatelet and anticoagulant
      drugs) remain poorly studied in the context of stroke in diabetes. This may
      relate to the accumulation of risk factors in type 2 diabetes as well as to
      diabetes-specific pathophysiologic factors. Regrettably, there is a lack of
      prospective evidence to support the efficacy of interventions in the secondary
      prevention of cerebrovascular events in type 2 diabetes, particularly recurrent
      stroke events. Overall, there is a need for rigorous evaluations of new
      therapeutic approaches in both primary and secondary prevention of stroke and
      management of acute stroke in patients with type 2 diabetes. This systematic
      review of the published literature summarizes the evidence regarding current
      therapeutic interventions and their impact on the risk of stroke in people with
      type 2 diabetes, and highlights potential strategies for improving outcomes.

PMID- 19399383
TI  - Concomitant spinal cord and vertebral body infarction is highly associated with
      aortic pathology: a clinical and magnetic resonance imaging study.
AB  - The purpose of this article is to investigate the relationship between clinical
      features and imaging characteristics of spinal cord infarction (SCI). Twenty
      patients (11 women/9 men) were diagnosed at the Chang Gung Memorial Hospital
      between March 1993 and March 2007. Data of clinical features, possible causes and
      imaging findings were collected and analyzed retrospectively. Their average age
      was 56.6 +/- 15.5 years. Possible causes of SCI were found in 16 patients (80%),
      including 8 (40%) who had a high risk of atherosclerosis, 5 (25%) who had aortic
      diseases, and 3 (15%) who had adjacent spinal diseases; the other 4 (20%) were
      cryptogenic. Seven patients had concomitant SCI and vertebral body infarctions,
      and four of them had aortic diseases. Most of the vertebral body infarctions were
      seen in the thoracolumbar regions (p = 0.008, chi(2) test) and were adjacent to
      their cord lesions. Twelve patients (60%) had poor outcomes (mortality, unable to
      walk, or able to walk with two aids). Younger patients (<or=55 year-old) with
      long cord lesions (greater than or equal to three vertebral segments) had poorer
      outcomes than older patients with short cord lesions. Vertebral abnormalities are
      not uncommon, but easily overlooked in SCI. Furthermore, concomitant SCI and
      vertebral body infarctions were usually located at the thoracolumbar regions, and
      highly associated with patients with aortic diseases (p = 0.03, chi(2) test). An
      understanding of the spinal cord and vertebral vascular supply greatly benefits
      in early diagnosis, etiological illumination, and prognostic prediction of SCI.

PMID- 19399382
TI  - Clinical implications of a possible role of vitamin D in multiple sclerosis.
AB  - Hypovitaminosis D is currently one of the most studied environmental risk factors
      for multiple sclerosis (MS) and is potentially the most promising in terms of new
      clinical implications. These practical consequences, which could be applied to MS
      patients without further delay, constitute the main purpose of this review.
      Vitamin D is involved in a number of important general actions, which were not
      even suspected until quite recently. In particular, this vitamin could play an
      immunomodulatory role in the central nervous system. Many and varied arguments
      support a significant role for vitamin D in MS. In animal studies, vitamin D
      prevents and improves experimental autoimmune encephalomyelitis.
      Epidemiologically, latitude, past exposure to sun and the serum level of vitamin
      D influence the risk of MS, with, furthermore, significant links existing between
      these different factors. Clinically, most MS patients have low serum levels of
      vitamin D and are in a state of insufficiency or even deficiency compared to the
      international norm, which has been established on a metabolic basis. Large
      therapeutic trials using vitamin D are still lacking but the first results of
      phase I/II studies are promising. In the meantime, while awaiting the results of
      future therapeutic trials, it can no longer be ignored that many MS patients have
      a lack of vitamin D, which could be detected by a serum titration and corrected
      using an appropriate vitamin D supplementation in order to restore their serum
      level to within the normal range. From a purely medical point of view, vitamin D
      supplementation appears in this light to be unavoidable in order to improve the
      general state of these patients. Furthermore, it cannot currently be ruled out
      that this supplementation could also be neurologically beneficial.

PMID- 19399384
TI  - Should lung scan be abandoned for pulmonary embolism diagnosis in the age of
      multislice spiral CT? No.

PMID- 19399385
TI  - Update on smoking cessation therapies.
AB  - As a reflection of an exponential increase in smoking rates throughout the world
      during the last century, the economic and human burden of mortality and morbidity
      related to smoking is now clearly defined. Smoking cessation is associated with
      health benefits for people of all ages. In this paper we provide a comprehensive
      review of current licensed pharmacological smoking cessation agents including
      efficacy and safety profiles, with comparisons of individual therapies available.
      Furthermore, we offer a prospective on the need for further testing of other
      agents including novel avenues of therapy.

PMID- 19399386
TI  - [Prevention and regenerative mechanisms in internal diseases].

PMID- 19399387
TI  - [Perspectives of regenerative mechanisms in cardiovascular disease spotlighting
      endothelial progenitor cells].
AB  - Cardiovascular diseases are the most common cause of death in the Western world.
      In general, the underlying disease is atherosclerosis, which is hallmarked by
      deterioration of the endothelial monolayer. Restoration of an intact endothelial
      monolayer for prevention and therapy of cardiovascular diseases is one key
      concept of regenerative medicine. This article offers a review of state-of-the
      art regenerative mechanisms in cardiovascular disease spotlighting endothelial
      progenitor cells, and further features the perspectives of regenerative medicine
      in vascular biology.

PMID- 19399388
TI  - [Physical activity for prevention and therapy of internal diseases in the
      elderly].
AB  - There is a growing number of elderly people in Western societies. Therefore, the
      prevalence of age-associated diseases increases. For most of these conditions,
      exercise and physical activity play a major role in the prevention and therapy.
      However, it is well established that the level of physical activity is lowest in
      elderly people. Physical fitness continues to be the most important protective
      health factor and should be improved in the elderly population. Many exercise
      recommendations include only endurance programs, but strength and coordination
      also deliver positive therapeutic effects in cardiovascular and metabolic
      diseases, lung diseases, neoplasms, and many other pathologic conditions
      including dementia. Age-specific recommendations should be included in exercise
      programs for health.

PMID- 19399389
TI  - [Measurement of physical activity in patients with chronic obstructive pulmonary
      disease].
AB  - Physical activity is an important parameter related to morbidity and mortality in
      cardiovascular disease, metabolic syndrome/diabetes, mental disorders, cancer,
      and chronic obstructive pulmonary disease (COPD). In COPD, lower levels of
      physical activity as reported by the patients are associated with a faster annual
      lung function decline, increased number of hospitalizations, and higher risk of
      mortality. Self-reported physical activity, however, correlates only poorly with
      objectively quantified physical activity in patients with COPD. Recent data show
      that physical activity can reliably be measured in a substantial number of
      patients with COPD. Extrapulmonary effects of COPD are associated with reduced
      physical activity. Clinical characteristics commonly used to assess disease
      severity like the forced expiratory volume in 1 s or the 6-min walk distance only
      incompletely reflect the physical activity of patients with COPD.

PMID- 19399390
TI  - [Erectile dysfunction: indicator of end-organ damage in cardiovascular patients].
AB  - Prevalence of erectile dysfunction (ED) amounts to 20-30% in a general population
      and increases to 50-70% in cardiovascular high-risk patients. Association of ED
      with known cardiovascular risk factors is causal with endothelial function of
      penile vessels and corpora cavernosa playing a crucial role in physiology of
      erection. Moreover, severity of ED correlates with cardiovascular risk of
      patients and represents an early symptom of generalized atherosclerosis. Hence,
      cardiovascular risk factors and diseases are sooner diagnosed in patients with ED
      with the opportunity of risk-adjusted prevention. Furthermore, different trials
      suggest erectile function as a strong predictor of cardiovascular events like
      myocardial infarction or stroke.

PMID- 19399392
TI  - [Making internal medicine attractive. 115th Internal Medicine Congress confronts
      young physicians].

PMID- 19399391
TI  - [Possibilities of telemedicine in arterial hypertension].
AB  - Telemetric blood pressure measurement opens a new dimension of cooperation
      between physician and patient. It requires clearly defined therapeutic target
      values. Telemonitoring is judged positively by 93% of patients treated this way
      for its exact and long-lasting observation mode by the treating physician. A
      better control of hypertension is possible due to adaption of therapy over a long
      observation period and exact blood pressure data by the treating physician and a
      better adherence to therapy by the patients. Besides good technical and logistic
      feasibility, published studies show a high acceptance both on the part of
      patients and treating physicians. Randomized, controlled and prospective studies
      showed significantly better blood pressure control of telemetrically observed
      patients compared to standard care. Telemedicine was exceptionally effective when
      combined with regular individualized interventions like phone calls. These data
      have to be confirmed by large prospective studies including "hard" endpoints and
      economic aspects. Of special interest is the telemetric observation in high-risk
      hypertensive patients like those with coronary artery disease, heart failure,
      cerebrovascular complications, or hypertension in pregnancy.

PMID- 19399393
TI  - The effect of brain-derived neurotrophic factor on angiogenesis.
AB  - To investigate the in vitro and in vivo proangiogenic effects of brain-derived
      neurotrophic factor (BDNF), human umbilical vein endothelial cells (HUVECs) were
      isolated and cultured in primary culture. The effect of BDNF on the proliferation
      of HUVECs was examined by MTT assay. The effects of BDNF on HUVEC migration and
      tube formation were studied by modified Boyden chamber assay and tube formation
      assay, respectively. Matrigel plug assay and chorioallantoic membrane assay were
      used to evaluate the effects of BDNF on angiogenesis in vivo. Our results showed
      that BDNF substantially stimulated the migration and tube formation of HUVECs in
      vitro, although it did not induce HUVEC proliferation. BDNF also induced
      angiogenesis both in matrigel plug of mouse model and in chick chorioallantoic
      membrane. In conclusion, BDNF can promote angiogenesis both in vitro and in vivo,
      and may be a proangiogenic factor.

PMID- 19399394
TI  - Influence of osteopontin short hairpin RNA on the proliferation and activity of
      rat vascular smooth muscle cells.
AB  - To investigate the influence of osteopontin (OPN) short hairpin RNA (shRNA) on
      the proliferation and activity of rat vascular smooth muscle cells (VSMCs), the
      expressing vector of shRNA targeting OPN was constructed and transferred into the
      rat VSMCs. After amplification and purification, pGenesil-1/OPNshRNA1 (PG1),
      pGenesil-1/OPNshRNA2 (PG2) and pGenesil-1/OPNshRNAHK (PGH) were transfected into
      the cultured rat VSMC by Lipofectamine 2000. Transfected cells were visualized by
      using an inverted fluorescent microscope. VSMCs transfected by optimal recombined
      plasmid was selected by culturing in G418 48 h later. Nude cells and cells
      transfected by PGH were used as control. The expression levels of OPN mRNA and
      protein were assayed by RT-PCR and Western blotting. The OPN of VSMCs was
      suppressed by transfection of optimal recombined plasmid, and the changes in cell
      proliferation, adhesion and motility were evaluated by MTT, adhesion test and
      transwell chamber test. Levels of type I and III collagen were measured with
      ELISA kit. Our results showed that VSMCs stably transfected by OPN shRNA
      accounted for over 50% of total cells. OPN mRNA and protein were reduced by 81%
      and 67% (P<0.01) by PG1, 73% and 52% (P<0.01) by PG2, respectively while no
      change was found in PGH and non-treated VSMCs. PG1 significantly suppressed the
      proliferation, adhesion, mobility of VSMCs and reduced the amount of type I and
      III collagen. It is concluded that recombinant plasmid can be successfully
      transfected into VSMCs by Lipofectamine 2000 and inhibit the expression of OPN.
      The proliferation, adhesion and mobility of VSMCs can be inhibited by knocking
      down OPN expression. Moreover, the transferring capability of cells is
      attenuated, and the secretion of type I and III collagen is inhibited after
      knocking-down of OPN expression. The study provides experimental evidence for
      clinical prevention of restenosis after percutaneous coronary intervention (PCI)
      by RNA interference (RNAi) technology.

PMID- 19399395
TI  - Enhanced expression of aquaporin-9 in rat brain edema induced by bacterial
      lipopolysaccharides.
AB  - To investigate the role of AQP9 in brain edema, the expression of AQP9 in an
      infectious rat brain edema model induced by the injection of lipopolysaccharide
      (LPS) was examined. Immunohistochemistry and reverse transcription-polymerase
      chain reaction (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA
      and protein at all observed intervals were significantly increased in LPS-treated
      animals in comparison with the control animals. Time-course analysis showed that
      the first signs of blood-brain barrier disruption and the increase of brain water
      content in LPS-treated animals were evident 6 h after LPS injection, with maximum
      value appearing at 12 h, which coincided with the expression profiles of AQP9
      mRNA and protein in LPS-treated animals. The further correlation analysis
      revealed strong positive correlations among the brain water content, the
      disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA
      and protein in LPS-treated animals. These results suggested that the regulation
      of AQP9 expression may play important roles in water movement and in brain
      metabolic homeostasis associated with the pathophysiology of brain edema induced
      by LPS injection.

PMID- 19399396
TI  - Quantitative autoradiographic study on receptor regulation in the basal ganglia
      in rat model of levodopa-induced motor complications.
AB  - In order to study neurotransmitter receptor regulation in the basal ganglia
      involved in the functional changes underlying levodopa-induced motor
      complications, quantitative autoradiography was used to observe receptor bindings
      of dopamine D1 and D2, N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5
      methylisoxazole propionic acid (AMPA) and amino butyric acid (GABA) in the basal
      ganglia of rats that had unilateral nigrostriatal lesions and had been
      chronically treated with levodopa until motor complications developed. The rats
      were randomly assigned to three groups: normal, denervated and treatment
      complicated groups. The results showed that response duration to levodopa became
      progressively shorter and abnormal involuntary movement (AIM) score was
      progressively increased during the course of levodopa treatment. Chronic
      treatment augmented D1 receptors more than denervation, and reduced D2 receptors
      that were also increased by dopamine denervation. Striatal NMDA receptors were
      substantially up-regulated in the treatment-complicated group. Levodopa treatment
      did not change receptors of nigral AMPA, pallidal GABA, and subthalamic GABA,
      which remained the same as that in denervation group. However, chronic treatment
      reversed the increase of nigral GABA receptors caused by the lesion. It was
      concluded that a shortening of response duration and AIM mimicked levodopa
      induced motor complications of Parkinson's patients. These data suggested that up
      regulation of dopamine D1 and NMDA receptors in the striatum leads to an
      imbalance of stimulation through the striatal output pathways, which is
      associated with levodopa-induced motor complications.

PMID- 19399397
TI  - Destruction of gastric cancer cells to mesothelial cells by apoptosis in the
      early peritoneal metastasis.
AB  - This study examined the mechanism by which the gastric cancer cells lead to early
      peritoneal metastasis. HMrSV5 cells, a human peritoneal mesothelial cell line,
      were co-incubated with the supernatants of gastric cancer cells. Morphological
      changes of HMrSV5 cells were observed. The cell damage was quantitatively
      determined by MTT assay. The apoptosis of HMrSV5 cells was observed under
      transmission electron microscope. Acridine orange/ethidium bromide-stained
      condensed nuclei was detected by fluorescent microscopy and flow cytometry. The
      expressions of Bcl-2 and Bax was immunochemically evaluated. The results showed
      that conspicuous morphological changes of apoptosis were observed in HMrSV5 cells
      24 h after treatment with the supernatants of gastric cancer cells. The
      supernatants could induce apoptosis of HMrSV5 cells in a time-dependent manner.
      The supernatants could up-regulate the expression of Bax and suppress that of Bcl
      2 in HMrSV5 cells. These findings demonstrated that gastric cancer cells can
      induce the apoptosis of HPMCs through supernatants in the early peritoneal
      metastasis. The abnormal expressions of Bcl-2 and Bax may contribute to the
      apoptosis. Anti-apoptosis drugs promise to be adjuvant chemotherapeutic agents in
      the treatment of peritoneal metastasis of gastric cancer.

PMID- 19399399
TI  - Circulating adhesion molecules in patients with Keshan disease and their
      relationship with Coxsackie B virus infection.
AB  - This study determined the levels of serum soluble intercellular adhesion molecule
      1 (sICAM-1) and soluble vascular cell adhesion molecular-1 (sVCAM-1) in patients
      with different types of Keshan disease (KD), examined the relationship between
      Coxsackie B virus-specific IgM antibody (CBV-IgM) and sICAM-1 or sVCAM-1 in KD
      patients, and investigated the role of these adhesion molecules in the
      pathogenesis of KD and their clinical implications. The levels of serum sICAM-1,
      sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in
      22 patients with chronic Keshan disease (CKD), 27 with latent Keshan disease
      (LKD) and 28 healthy controls. The subjects in different groups were adjusted for
      sex and age. Echocardiography was adopted to determine left ventricular ejection
      fraction (LVEF) in 22 patients with CKD. The results showed that CKD patients had
      significantly higher levels of sICAM-1 and sVCAM-1 than LKD patients and healthy
      controls (P<0.01 for all). And there was significant difference in the levels of
      the 2 adhesion molecules between LKD patients and healthy controls (P<0.05). A
      negative correlation was found between LVEF and sICAM-1 or sVCAM-1 in CKD
      patients. The percentage of CBV-specific IgM positive individuals in KD patients
      was significantly higher than that of healthy controls. In CVB-specific IgM
      positive patients, the levels of serum sICAM-1 and sVCAM-1 were significantly
      greater than those in CBV-specific IgM negative counterpart. It was concluded
      that the increase in the levels of sICAM-1 and sVCAM-1 suggests the progression
      of inflammation in KD. sICAM-1 and sVCAM-1 can promote the development of
      myocardial pathology and lead to poor myocardial function. The increased serum
      sICAM-1 and sVCAM-1 in KD patients may be related to CBV infection.

PMID- 19399398
TI  - Tea polyphenols exerts anti-hepatitis B virus effects in a stably HBV-transfected
      cell line.
AB  - In this study, the anti-HBV effects of tea polyphenols (TP) were examined. After
      cells were exposed to TP for 3, 6, 9 days, amounts of HBsAg, HBeAg and HBV-DNA
      released into the supernatant of the cultured HepG2 2.2.15 cells were detected.
      TP, to some extent, inhibited the secretion of HBsAg and strongly suppressed the
      secretion of HBeAg in a dose-dependent (P<0.01) and time-dependent manner, with
      50% maximal inhibitory concentration (IC50) value being 7.34 microg/mL on the 9th
      day, but the time-dependence was not significant (P=0.051). Expression of HBV-DNA
      in the supernatant of the cell culture also was significantly decreased in a dose
      dependent fashion (P<0.01). The IC50 of TP in inhibiting HBV DNA was 2.54
      microg/mL. It concluded that TP possessed potential anti-HBV effects and may be
      used as a treatment alternative for HBV infection.

PMID- 19399400
TI  - ANG II-AT1 receptor pathway is involved in the anti-fibrotic effect of beta
      elemene.
AB  - To investigate the effects of beta-elemene on the ANG II-AT1 receptor pathway in
      rats with liver fibrosis, a model of hepatic fibrosis was induced by hypodermical
      injection of carbon tetrachloride (CCl4) into Wistar male rats. beta-elemene was
      intraperitonealy administered into the rats for 8 weeks (0.1 mL/100 g body weight
      per day). Masson staining was used to observe the liver fibrosis of rats and
      liver functions were measured by enzymatic kinetic analysis. The content of
      hydroxyproline in liver tissues was detected by specimen alkaline hydrolysis. The
      level of plasma ANG in blood II plasma was detected by radioimmunoassay. The
      expression of AT1R in rat liver were measured using reverse transcriptional
      polymerase chain reaction and immunohistochemistry respectively. The results
      showed that beta-elemene could reduce the collagen disposition in liver and
      inhibit the progression of liver fibrosis. In addition, the levels of plasma ANG
      II and the expression of hepatic AT1R in rats with liver fibrosis were also
      suppressed by beta-elemene. It is concluded that the ANG II-AT1 receptor pathway
      plays an important role in the development of hepatic fibrosis and beta-elemene
      could down-regulate the levels of plasma ANG II and the expression of hepatic
      AT1R in rats with liver fibrosis.

PMID- 19399401
TI  - Endocannabinoids anandamide and its cannabinoid receptors in liver fibrosis after
      murine schistosomiasis.
AB  - This study examined endogenous cannabinoid (ECB)-anandamide (AEA) and its
      cannabinoid receptors (CBR) in mice liver with the development of schistosoma
      japonicum. Mice were infected with schistosoma by means of pasting the cercaria
      onto their abdomens. Liver fibrosis was pathologically confirmed nine weeks after
      the infection. High performance liquid chromatography (HPLC) was employed to
      determine the concentration of AEA in the plasma of mice. Immunofluorescence was
      used to detect the expression of CBR1 and CBR2 in liver tissue. Morphological
      examination showed typical pathological changes, with worm tubercles of
      schistosoma deposited in the liver tissue, fibrosis around the worm tubercles and
      infiltration or soakage of inflammatory cells. Also, CBR1 and CBR2 were present
      in hepatocytes and hepatic sinusoids of the two groups, but they were obviously
      enhanced in the schistosoma-infected mice. However, the average optical density
      of CBR1 in the negative control and fibrosis group was 13.28+/-7.32 and 30.55+/
      7.78, and CBR2 were 28.13+/-6.42 and 52.29+/-4.24 (P<0.05). The levels of AEA in
      the fibrosis group were significantly increased as compared with those of the
      control group. The concentrations of AEA were (0.37+/-0.07) and (5.67+/-1.34)
      ng/mL (P<0.05). It is concluded that the expression of endocannabinoids AEA and
      its cannabinoid receptor CBR were significantly increased in schistosoma-infected
      mice. Endogenous endocannabinoids may be involved in the development of
      schistosoma-induced liver fibrosis.

PMID- 19399402
TI  - The effects of HBx gene on the expression of DNA repair enzymes hOGG1 and
      hMYHalpha mRNA in HepG2 cells.
AB  - To observe the alteration in the expression of DNA repair enzymes hOGG1 and
      hMYHalpha and the change in 8-OHdG levels in the HBx gene-transfected cells
      HepG2/HBx and to explore the mechanisms of the HBV-associated hepatocellular
      carcinoma, the gene-transfected cells HepG2/HBx which stably expressed HBx was
      established, and the effect of HBx on the cell cycle and proliferation of HepG2
      was examined. By using the beta-actin as the interior control, real-time
      polymerase chain reaction (Real-time qPCR) was employed to quantitatively detect
      the expression of DNA repair enzymes hOGG1 and hMYHalpha in the HepG2/HBx, the
      control cells HepG2 and HepG2 transfected with pcDNA3.1 vector (HepG2/pDNA3.1).
      The 8-OHdG levels were determined by HPLC/ECD in the established gene-transfected
      cells HepG2/HBx and the control cells HepG2 and HepG2/pcDNA3.1. Our results
      showed that the expression of DNA repair enzyme hMYHalpha in the HepG2/HBx
      (0.021+/-0.007) was significantly lower than that of HepG2 (0.099+/-0.041)
      (P<0.05) and HepG2/pDNA3.1 (0.121+/-0.005) (P<0.05). However, the no significant
      differences existed in the expression of DNA repair enzyme hOGG1 among the three
      cell strains (P>0.05). The 8-OHdG level in the HepG2/HBx was significantly higher
      than that in HepG2 and HepG2/pcDNA3.1 (P<0.05). It is concluded that HBx gene may
      inhibit the expression of DNA repair enzyme hMYHalpha mRNA to impair the ability
      to repair the intracellular DNA oxidative damage, to increase the oxidative DNA
      adduct 8-OHdG and to affect the nucleotide excision repair function, thus
      participate in the occurrence and development of hepatocellular carcinoma.

PMID- 19399403
TI  - Dynamic expressions of liver tissue apoptosis-related genes of Vibrio vulnificus
      sepsis rats and the effects of antibacterial agents.
AB  - Dynamic changes in mRNA expressions of liver tissue apoptosis-promoting genes Fas
      and Bax and apoptosis-inhibiting gene Bcl-2 of vibrio vulnificus sepsis rats were
      detected and the effects of antibacterial agents were examined. The rat model
      with Vibrio vulnificus sepsis (VV group) was established and some of the Vibrio
      vulnificus sepsis rats were treated with antibacterial agents (AA group). The
      mRNA expressions of Fas, Bax and Bcl-2 were measured by reverse transcription
      polymerase chain reaction (RT-PCR). As compared with normal control group (NC
      group), the expressions of Fas and Bax mRNA in liver tissue at all different time
      points in VV group were increased significantly (P<0.05), and the highest levels
      of Fas and Bax mRNA expressions were 6 and 12 h after the infection,
      respectively. At the same time, the expression of Bcl-2 mRNA in liver tissue at
      all different time points in VV group were decreased significantly (P<0.05), and
      the lowest level of Bcl-2 mRNA expression appeared 2 h after the infection. The
      mRNA expressions of Bcl-2 in liver tissue 9 and 12 h after the infection in AA
      group were increased significantly (P<0.05) compared with NC group, while the
      expressions of Fas and Bax mRNA were not significantly different from those of NC
      group. Compared with VV group, the expression of Fas mRNA in AA group was
      decreased (P<0.05) and Bax mRNA was decreased significantly 12 and 16 h after the
      infection (P<0.05), while the expressions of Bcl-2 mRNA were increased
      significantly 9, 12 and 16 h after the infection (P<0.05). It is concluded that
      the mRNA expressions of liver tissue apoptosis-promoting genes Fas and Bax were
      increased remarkably in vibrio vulnificus sepsis rats, whereas the expression of
      apoptosis-inhibiting gene Bcl-2 mRNA was decreased obviously in sepsis rats in
      early stage. The treatment with cefoperazone sodium and levofloxacin lactate
      could inhibit the expression of Fas mRNA and Bax mRNA and enhance the expression
      of Bcl-2 mRNA at the same time.

PMID- 19399404
TI  - Inhibitory effect of extract of fungi of Huaier on hepatocellular carcinoma
      cells.
AB  - This study investigated the inhibitory effect of the extract of fungi of Huaier
      (EFH) on the growth of hepatocellular carcinoma (HCC) cells. Hep-G2 cells, a
      human HCC cell line, were cultured in DMEM containing 10% fetal bovine serum and
      treated with EFH of different concentrations (1, 2, 4, 8 mg/mL) for 24, 48 and 72
      h respectively. The apoptosis rate of the cells was flow cytometrically measured.
      Thirty-six tumor-bearing New Zealand rabbits were randomly divided into 3 groups:
      group A (control group), in which the rabbits were infused with 0.2 mL/kg normal
      saline via the hepatic artery; group B (transhepatic artery chemoembolization
      [TACE] group), in which the rabbits were given lipiodol at 0.2 mL/kg plus MMC at
      0.5 mg/kg via the hepatic artery; group C (TACE+EFH group), in which EFH (500
      mg/kg) were orally administered after TACE. Two weeks after TACE, the rabbits
      were sacrificed and the implanted tumors were sampled. The tumor volume and the
      necrosis rate were determined. The tumor tissues were immunohistochemically
      detected for the expressions of factor VIII, VEGF, P53, Bax and Bcl-2. The
      microvessel density (MVD) was calculated by counting the factor VIII-positive
      endothelial cells. Our results showed that after treatment with EFH, the
      apoptosis rate of Hep-G2 cells was enhanced in a concentration- and time
      dependent manner. Two weeks after the treatment, the average tumor volume, the
      necrosis rate and the growth rate of the implanted tumor in group C were
      significantly different from those in groups A and B (P<0.05). MVD and VEGF
      expressions were significantly decreased in the group C when compared with those
      in groups B (P<0.05 for all). The Bax expression was weakest in group A and
      strongest in group C. The expressions of P53 and Bcl-2 were minimal in group C
      and maximal in group A. There were significant differences in the expressions of
      P53, Bax and Bcl-2 among the 3 groups (P<0.05 for all) and there was significant
      difference between group B and group C (P<0.05). It was concluded that EFH could
      suppress not only the growth of HCC cells but also tumor angiogenesis and it can
      induce the apoptosis of HCC cells. EFH serves as an alternative for the treatment
      of HCC.

PMID- 19399405
TI  - The effects of PDTC plus leflunomide and cyclosporine on the NF-kappaB signaling
      pathway in mouse-to-rat cardiac xenografts.
AB  - In this study, the effects of pirrolidine dithiocarbamate (PDTC) plus leflunomide
      (Lef) and cyclosporine (CsA) on the NF-kappaB signaling pathway in mouse-to-rat
      cardiac xeno-transplantation models were investigated. NIH mice and Wistar rats
      served as donors and recipients respectively. Mouse-to-rat cardiac
      xenotransplantation was performed. The recipients were divided into 5 groups:
      group A (the control group), group B (PDTC group), group C (PDTC plus CsA group),
      group D (PDTC plus Lef group) and group E (PDTC plus Lef and CsA group). The
      expressions of IKKalpha/beta, NF-kappaB-P65, IkappaBalpha, ICAM-1 and NF-kappaB
      DNA binding activity in xenograft tissues were determined by immunohistochemistry
      and Western blot as well as electrophoretic mobility shift assay (EMSA). The
      median survival time of cardiac xenografts in the control group, PDTC group, PDTC
      plus CsA group, PDTC plus Lef group and PDTC plus Lef and CsA group was (2.17+/
      0.41), (2.33+/-0.52), (4.67+/-1.21), (7.00+/-1.79) and (9.00+/-1.41) days
      respectively. The survival time of xenografts in the PDTC plus Lef and CsA group
      was significantly longer than that in other four groups (P<0.05 for all), that in
      the PDTC plus Lef group longer than that in the control group, PDTC group and
      PDTC plus CsA group (P<0.05 for all), that in PDTC plus CsA group longer than the
      control group and PDTC group (P<0.05 for all). The expressions of IKKalpha/beta,
      NF-kappaB-P65, IkappaBalpha and ICAM-1 and NF-kappaB DNA binding activity were
      notably increased in mouse-to-rat cardiac xenografts. The expressions were
      decreased in the control group, PDTC group, PDTC plus CsA group, PDTC plus Lef
      and PDTC plus Lef and CsA group in turn. It was concluded that PDTC plus Lef and
      CsA can significantly suppress the expressions of IKKalpha/beta, NF-kappaB-P65,
      IkappaBalpha, ICAM-1 and NF-kappaB DNA binding activity, thereby prolonging the
      survival of the cardiac xenografts.

PMID- 19399406
TI  - Surgical treatment of aortic aneurysm and aortic dissection: a retrospective
      analysis of 122 cases.
AB  - The study summarizes the clinical experience of surgical treatments of various
      types of thoracic aneurysm and aortic dissection. Clinical data of 122 patients
      with thoracic aneurysm and aortic dissection during July 2005 to July 2008 were
      retrospectively analyzed. The elective operations were performed in 107 patients
      while emergency surgery was done in 15 cases. Different surgical strategies were
      employed on the basis of diseased region, including simple ascending aortic
      replacement (n=3), aortic root replacement (n=43), hemi-arch replacement /total
      arch replacement+elephant trunk technique (n=32), thoracic/thoracoabdominal
      aortic replacement (n=8) and endovascular repair (n=36). In this series, there is
      4 cases of perioperative death due to massive cerebral hemorrhage (n=1),
      respiratory failure (n=1) and multiple organ dysfunction syndrome (MODS) (n=2).
      Three cases developed post-operative massive cerebral infarction and the
      relatives of the patients abandoned treatment. Instant success rate of
      endovascular repair was 100%. The intimal rupture was sealed. Blood flow was
      unobstructed in true lumen and no false lumen was visualized. It was concluded
      that aggressive surgery should be considered in the patients with thoracic
      aneurysm and aortic dissection. Surgical procedures should vary with the location
      and the nature of the lesions.

PMID- 19399407
TI  - The inhibitory effect of astilbin on the arteriosclerosis of murine thoracic
      aorta transplant.
AB  - The inhibitory effect of astilbin on transplant arteriosclerosis in murine model
      of thoracic aorta transplantation was examined. Model of rat thoracic aorta
      transplantation was established. Ninety rats were divided into three groups. In
      isograft group, the thoracic aorta of Brown Norway (BN) rat was anastomosed with
      the abdominal aorta of another BN rat. In allograft group, the thoracic aorta of
      BN rat was anastomosed with the abdominal aorta of Lewis rat. In astilbin group,
      the rats receiving allo-transplantation were given astilbin 5 mg/kg per day for a
      time of 28 days. The donor thoracic aorta and the recipient abdominal aorta were
      anastomosed by means of a polyethylene cannula (inner diameter: 1.5 mm, length: 3
      mm length). The grafts were histologically examined for structural changes. The
      areas of arterial lumen and endatrium were calculated. Our results showed that,
      in the allograft group, 28 days after allografting, conspicuous proliferation of
      smooth muscles and infiltration with a great number of inflammatory cells were
      found in the tunica intima and tunica media. Astilbin significantly inhibited the
      proliferation of smooth muscles and ameliorated the infiltration of inflammatory
      cells thereby prevent against the development of transplant arteriosclerosis. It
      is concluded that asltilbin can effectively prevent the development of
      arteriosclerosis in allotransplant by inhibiting the proliferation of smooth
      muscles and inhibit the proliferation of smooth muscles in tunica of intima and
      media and reducing infiltration of the inflammatory cells.

PMID- 19399408
TI  - Effects on biological behavior of bladder carcinoma T24 cells via silencing DNMT1
      and/or DNMT3b with shRNA in vitro.
AB  - In this study, RNA interference technique was employed to silence the expression
      of DNMT1 and/or DNMT3b in human bladder cancer T24 cells. The expression levels
      of their mRNA and protein were greatly decreased by up to 75% and 65%
      respectively after T24 cells were transfected with lipofectamine2000 for 72 h,
      indicating RNA interference is an effective tool in gene knockdown. Proliferation
      and apoptosis of T24 cells were detected by MTT, and annexin-V-FITC and propidium
      iodide staining flow cytometry, respectively. It was found that loss of the DNMT1
      or DNMT3b expression could inhibit the cell growth and promote the cell apoptosis
      to some extent. However, combined treatment with shRNA targeting both DNMT1 and
      DNMT3b mRNA could obviously enhance the above effects. It was concluded that
      simultaneously silencing both genes could result in strong suppressing effect on
      tumor proliferation and promoting cell apoptosis than separate use, suggesting
      combined use of DNMT1 and DNMT3b can achieve a synergistic effect in the CpG
      island methylation in human bladder tumorigenesis.

PMID- 19399409
TI  - Identification of differently expressed genes in chemical carcinogen-induced rat
      bladder cancers.
AB  - Possible altered gene expression patterns in bladder tumour carcinogenesis in rat
      bladder cancers induced by BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] was
      examined by cDNA microarray analysis of gene expression profiles. Thirty Sprague
      Dawley rats were given drinking water containing 0.05% BBN ad libitum for 24 to
      28 weeks. Equal numbers of control rats were given tap water without BBN. After
      treatment, the rat bladders were excised for RNA extraction and histopathological
      examinations. Total RNAs were extracted from rat transitional cell carcinoma
      (TCC) tissues and micro-dissected normal rat bladder epithelia. The atlas glass
      rat microarray was used, which included oligonucleotides of 1081 rat genes. Some
      of the up-regulated genes in rat bladder TCCs were further confirmed by Northern
      blotting. Our results showed that the transcriptions of 30 genes were
      significantly elevated in the rat bladder TCCs, and these included fly proto
      oncogene, Lipocortin 2, COX IV, COX V a, and cathepsin D. Also, 15 genes were
      significantly down-regulated in the rat bladder TCCs and they included B7.1,
      TNFr1, APOA1 and VHL. The results of cDNA microarray analysis demonstrated that
      normal rat bladder epithelia and bladder TCC exhibited different and specific
      gene statement profiles. The increased expressions of the identified genes may
      play an important role in the chemically induced bladder carcinogenesis.

PMID- 19399410
TI  - Effects of ghrelin on the proliferation and differentiation of 3T3-L1
      preadipocytes.
AB  - The effects of ghrelin on the proliferation and differentiation of 3T3-L1
      preadipocytes and the possible mechanisms were investigated in this study. 3T3-L1
      preadipocytes were cultured in vitro and treated with different concentrations of
      ghrelin. Proliferation of 3T3-L1 preadipocytes was evaluated by MTT method and
      mRNA levels of c-myc and thymidine kinase were detected by RT-PCR. Morphological
      changes of 3T3-L1 preadipocytes were observed and cell differentiation was
      measured by oil red O staining. The mRNA levels of peroxisome proliferator
      activated receptor gamma (PPARgamma) and CAAT/enhancer binding protein
      (C/EBPalpha) in the cells at different differentiation stages were detected by RT
      PCR. The results showed that ghrelin at concentrations of 10(-7) to 10(-15) mol/L
      could significantly promote preadipocyte proliferation (P<0.05), with the most
      pronounced effect observed at 10(-11) mol/L (P<0.01). Treatment of 3T3-L1
      preadipocytes with ghrelin significantly increased the mRNA levels of c-myc and
      thymidine kinase (P<0.01). Morphological findings demonstrated that the great
      amount of lipid droplets appeared in the 3T3-L1 preadipocytes treated with
      ghrelin. Ghrelin could morphologically induce the differentiation of 3T3-L1
      preadipocytes into mature adipocytes. Ghrelin significantly increased the mRNA
      levels of PPARgamma and C/EBPalpha during the differentiation, when compared with
      control group (P<0.05). The mRNA levels of PPARgamma and C/EBPalpha were
      obviously up-regulated with the differentiation of preadipocytes after the
      treatment of ghrelin. There were significant difference in the mRNA levels of
      PPARgamma and C/EBPalpha on day 2 and day 8 of the differentiation of 3T3-L1
      preadipocytes (P<0.01). In conclusion, ghrelin could promote the proliferation
      and differentiation of 3T3-L1 preadipocytes by increasing the mRNA levels of
      PPARgamma and C/EBPalpha and therefore enhance the sensitivity of adipocytes
      against insulin.

PMID- 19399412
TI  - Superparamagnetic iron oxide labeling of spinal cord neural stem cells
      genetically modified by nerve growth factor-beta.
AB  - This study established superparamagnetic iron oxide (SPIO)-labeled nerve growth
      factor-beta (NGF-beta) gene-modified spinal cord-derived neural stem cells
      (NSCs). The E14 rat embryonic spinal cord-derived NSCs were isolated and
      cultured. The cells of the third passage were transfected with plasmid pcDNA3
      hNGFbeta by using FuGENE HD transfection reagent. The expression of NGF-beta was
      measured by immunocytochemistry and Western blotting. The positive clones were
      selected, allowed to proliferate and then labeled with SPIO, which was mediated
      by FuGENE HD transfection reagent. Prussian blue staining and transmission
      electron microscopy (TEM) were used to identify the SPIO particles in the cells.
      The distinctive markers for stem cells (nestin), neuron (beta-III-tubulin),
      oligodendrocyte (CNPase) and astrocyte (GFAP) were employed to evaluate the
      differentiation ability of the labeled cells. The immunocytochemistry and western
      blotting showed that NGF-beta was expressed in spinal cord-derived NSCs. Prussian
      blue staining indicated that numerous blue-stained particles appeared in the
      cytoplasma of the labeled cells. TEM showed that SPIO particles were found in
      vacuolar structures of different sizes and the cytoplasma. The
      immunocytochemistry demonstrated that the labeled cells were nestin-positive.
      After differentiation, the cells expressed beta-III-tubulin, CNPase and GFAP. It
      was concluded that the SPIO-labeled NGF-beta gene-modified spinal cord-derived
      NSC were successfully established, which are multipotent and capable of self
      renewal.

PMID- 19399411
TI  - Immortalization of human precartilaginous stem cells by transfecting SV40Tag.
AB  - Immortalized human precartilaginous stem cells (IPSCs) were established to
      provide stable cell resource for the study of the molecular mechanism of gene
      targeting on the differentiation of PSCs. Plasmid pCMVSV40T/PUR containing simian
      virus 40 large T antigen gene (SV40Tag) was transfected into human PSCs by using
      lipofectin transfection. Colonies were isolated by puromycin selection and
      expanded by multiple passages. Immunohistochemistry, RT-PCR and Southern blotting
      were used to identify the transfected cells and to detect the expression and
      integration of SV40Tag in expanded cell lines. The positive colonies were
      isolated and subcultured, designated immortalized precartilaginous stem cells
      (IPSCs), which were confirmed as fibroblast growth factor receptor-3 (FGFR-3)
      positive cells by immunohistochemistry and RT-PCR. SV40Tag cDNA was found in
      cultured IPSCs of passage 8 by Southern blotting, and the expressions of SV40Tag
      mRNA and protein were confirmed by RT-PCR. These findings suggested that IPSCs
      strain with SV40Tag was constructed successfully.

PMID- 19399413
TI  - Chitosan/pshRNA plasmid nanoparticles targeting MDR1 gene reverse paclitaxel
      resistance in ovarian cancer cells.
AB  - In order to investigate the effect of chitosan/pshRNA plasmid nanoparticles
      targeting MDR1 genes on the resistance of A2780/TS cells to paclitaxel,
      chitosan/pshRNA plasmid nanoparticles were synthesized by means of a complex
      coacervation technique and transfected into A2780/TS cells. The cells transfected
      with MDR1-targeted chitosan/pshRNA plasmid nanoparticles were experimental cells
      and the cells transfected with chitosan/pGPU6/GFP/Neo no-load plasmid
      nanoparticles served as negative control cells. Morphological features of the
      nanoparticles were observed under transmission electron microscope (TEM). MDR1
      mRNA expression was assessed by RT-PCR. Half-inhibitory concentration (IC50) of
      paclitaxel for A2780/TS cells was determined by MTT method. TEM showed that the
      nanoparticles were round-shaped, smooth in surface and the diameters varied from
      80 to 120 nm. The MDR1 mRNA in the transfected cells was significantly decreased
      by 17.6%, 27.8% and 52.6% on the post-transfection day 2, 4 and 7 when compared
      with that in A2780/TS cells control (P<0.05). MTT assay revealed that the
      relative reversal efficiency was increased over time and was 29.6%, 51.2% and
      61.3% respectively in the transfected cells 2, 4, 7 days after transfection and
      IC50 (0.197+/-0.003, 0.144+/-0.001, 0.120+/-0.004) were decreased with difference
      being significant when compared with that in A2780/TS (0.269+/-0.003) cells
      control (P<0.05). It was concluded that chitosan/pshRNA plasmid nanoparticles
      targeting MDR1 can effectively reverse the paclitaxel resistance in A2780/TS
      cells in a time-dependent manner.

PMID- 19399414
TI  - Endothelial nitric oxide synthase traffic inducer in the umbilical vessels of the
      patients with pre-eclampsia.
AB  - The expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) was
      examined in the umbilical vessels of the patients with pre-eclampsia (PE) to
      explore its possible role in the pathogenesis of PE. The NOSTRIN mRNA in
      umbilical tissues was determined by RT-PCR. The eNOS activity in umbilical
      vessels was spectrophotometrically detected. NO2-/NO3-, the stable metabolic end
      products of NO, was measured by using nitrate reductase. RT-PCR showed that the
      expression level of NOSTRIN was significantly higher in women with PE than in the
      normal group (P<0.01). The activity of eNOS was significantly decreased in PE
      group [(12.83+/-3.61) U/mg] than in normal group [(21.72+/-3.83) U/mg] (P<0.01).
      The level of NO2-/NO3- in PE patients (27.53+/-7.48) micromol/mg was
      significantly lower than that of normal group (54.27+/-9.53) micromol/mg
      (P<0.01). The significant negative correlation existed between the expression of
      NOSTRIN and the activity of eNOS in umbilical vessels of women with PE (r=-0.58,
      P<0.01). It was concluded that the level of NOSTRIN expression was increased in
      umbilical vessel of women with PE, indicating that it may be involved in the
      pathogenesis of PE.

PMID- 19399415
TI  - Expression of phosphorylated-STAT3 and osteopontin and their correlation in
      melanoma.
AB  - The expressions of p-STAT3 and osteopontin in 22 cases of normal nevi and 43
      cases of malignant melanoma were immunohistochemically detected, and the
      correlation between p-STAT3 and osteopontin in malignant melanoma and the
      correlations of p-STAT3 (or osteopontin) with invasion, metastasis and thickness
      of malignant melanoma were examined. The results showed p-STAT3 was expressed in
      2 of 22 cases of normal nevi and 30 of 43 cases of malignant melanoma, while
      osteopontin was expressed in 3 cases of normal nevi and 29 cases of malignant
      melanoma. The expressions of p-STAT3 and osteopontin in melanoma were
      significantly higher than that in benign nevi. There existed significant
      correlations between the expression of p-STAT3 and that of osteopontin in
      melanoma. Furthermore, the expression rates of p-STAT3 were significantly higher
      in invasive or metastatic melanomas than that their non-invasive or non
      metastatic counterparts, and the expression rates of osteopontin were
      significantly higher in invasive melanomas than that in non-invasive ones. It is
      concluded that p-STAT3 and osteopontin may play important roles in the
      pathogenesis of malignant melanoma.

PMID- 19399416
TI  - The longitudinal sagittal growth changes of maxilla and mandible according to
      quantitative cervical vertebral maturation.
AB  - To investigate the longitudinal sagittal growth changes of maxilla and mandible
      according to the quantitative cervical vertebral maturation (QCVM) for
      adolescents with normal occlusion, mixed longitudinal data were used. The samples
      included 87 adolescents aged from 8 to 18 y old with normal occlusion (32 males,
      55 females) selected from 901 candidates. Sequential lateral cephalograms and
      hand-wrist films were taken once a year, lasting for 6 y. The longitudinal
      sagittal growth changes of maxilla and mandible according to QCVM were measured.
      There were some significant differences between maxilla and mandible according to
      QCVM. The sagittal growth change of maxilla showed a trend towards high velocity-
      >decelerating velocity-->completing velocity from QCVM stage I to stage IV. The
      sagittal growth change of mandible showed a trend towards accelerating velocity-
      >high velocity-->decelerating velocity-->completing velocity from QCVM stage I to
      stage IV. With sagittal relationship, growth magnitude was almost the same
      between maxilla and mandible at QCVM stage I. At stage II the growth of mandible
      exceeded that of maxilla and growth in mandible continued at stages III and IV,
      while the maxilla ceased to grow. Growth magnitude was greater and the growth
      duration was longer with male mandible. It is concluded that the longitudinal
      sagittal growth changes of maxilla and mandible on the basis of QCVM is of value
      in the orthodontic practice.

PMID- 19399417
TI  - Evaluation of atrial septal defect using real-time three-dimensional
      echocardiography: comparison with surgical findings.
AB  - The present study evaluated the application of three dimensional echocardigraphy
      (3DE) in the diagnosis of atrial septal defect (ASD) and the measurement of its
      size by 3DE and compared the size with surgical findings. Two-dimensional and
      real-time three dimensional echocardiography (RT3DE) was performed in 26 patients
      with atrial septal defect, and the echocardiographic data were compared with the
      surgical findings. Significant correlation was found between defect diameter by
      RT3DE and that measured during surgery (r=0.77, P<0.001). The defect area changed
      significantly during cardiac cycle. Percentage change in defect size during
      cardiac cycle ranged from 6%-70%. Our study showed that the size and morphology
      of atrial septal defect obtained with RT3DE correlate well with surgical
      findings. Therefore, RT3DE is a feasible and accurate non-invasive imaging tool
      for assessment of atrial septal size and dynamic changes.

PMID- 19399418
TI  - The univariate and bivariate impact of HIV/AIDS on the quality of life: a cross
      sectional study in the Hubei Province-Central China.
AB  - This study is aimed to evaluate the quality of life (QOL) for individuals living
      with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
      in Hubei province-central China by using WHOQOL-BREF instrument (Chinese
      version). One hundred and thirty six respondents (HIV/AIDS individuals) attending
      out-patient department of Chinese Center for Disease Control and Prevention
      (Chinese CDC) were administered a structured questionnaire developed by
      investigators. QOL was evaluated by using WHOQOL-BREF instrument (Chinese
      version). The results showed that the mean score of overall QOL on a scale of 0
      100 was 25.8. The mean scores in 4 domains of QOL on a scale of 0-100 were 82.9
      (social domain), 27.5 (psychological domain), 17.7 (physical domain) and 11.65
      (environmental domain). The significant difference of QOL was noted in the score
      of physical domain between asymptomatic (14.6) and early symptomatic individuals
      (12) (P=0.014), and between patients with early symptoms (12) and those with AIDS
      (10.43) (P<0.001). QOL in psychological domain was significantly lower in early
      symptomatic (12.1) (P<0.05) and AIDS patients (12.4) (P<0.006) than in
      asymptomatic individuals (14.2). The difference in QOL scores in the
      psychological domain was significant with respect to the income of patients
      (P<0.048) and educational status (P<0.037). Significantly better QOL scores in
      the physical domain (P<0.040) and environmental domain (P<0.017) were noted with
      respect to the occupation of the patients. Patients with family support had
      better QOL scores in environmental domain. In our research, QOL for HIV/AIDS
      individuals was associated with education, occupation, income, family support and
      clinical categories of the patients. It was concluded that WHOQOL-BREF Chinese
      version was successfully used in the evaluation of QOL of HIV/AIDS individuals in
      Chinese population and proved to be a reliable and useful tool.

PMID- 19399419
TI  - Nursing-related patient safety events in hospitals.
AB  - To explore the method of identifying nursing-related patient safety events,
      types, contributing factors and evaluate consequences of these events in
      hospitals of China, incident report program was established and implemented in 15
      patient units in two teaching hospitals of China to get the relevant information.
      Among 2935 hospitalized patients, 141 nursing-related patient safety events were
      reported by nurses. Theses events were categorized into 15 types. Various factors
      contributed to the events and the consequence varied from no harm to patient
      death. Most of the events were preventable. It is concluded that incident
      reporting can provide more information about patient safety, and establishment of
      a program of voluntary incident reporting in hospitals of China is not only
      urgent but also feasible.

PMID- 19399426
TI  - Rapid creation, Monte Carlo simulation, and visualization of realistic 3D cell
      models.
AB  - Spatially realistic diffusion-reaction simulations supplement traditional
      experiments and provide testable hypotheses for complex physiological systems. To
      date, however, the creation of realistic 3D cell models has been difficult and
      time-consuming, typically involving hand reconstruction from electron microscopic
      images. Here, we present a complementary approach that is much simpler and
      faster, because the cell architecture (geometry) is created directly in silico
      using 3D modeling software like that used for commercial film animations. We show
      how a freely available open source program (Blender) can be used to create the
      model geometry, which then can be read by our Monte Carlo simulation and
      visualization softwares (MCell and DReAMM, respectively). This new workflow
      allows rapid prototyping and development of realistic computational models, and
      thus should dramatically accelerate their use by a wide variety of computational
      and experimental investigators. Using two self-contained examples based on
      synaptic transmission, we illustrate the creation of 3D cellular geometry with
      Blender, addition of molecules, reactions, and other run-time conditions using
      MCell's Model Description Language (MDL), and subsequent MCell simulations and
      DReAMM visualizations. In the first example, we simulate calcium influx through
      voltage-gated channels localized on a presynaptic bouton, with subsequent
      intracellular calcium diffusion and binding to sites on synaptic vesicles. In the
      second example, we simulate neurotransmitter release from synaptic vesicles as
      they fuse with the presynaptic membrane, subsequent transmitter diffusion into
      the synaptic cleft, and binding to postsynaptic receptors on a dendritic spine.

PMID- 19399427
TI  - Systems approach to therapeutics design.
AB  - A general methodology is described for improving the therapeutic properties of
      protein drugs by engineering novel intracellular trafficking pathways. Procedures
      for cellular trafficking experiments and mathematical modeling of trafficking
      pathways are presented. Previous work on the engineering of the transferrin
      trafficking pathway will be used to illustrate how each step of the methodology
      can be applied.

PMID- 19399428
TI  - Microfluidics technology for systems biology research.
AB  - Systems biology is a discipline seeking to understand the emergent behavior of a
      biological system by integrative modeling of the interactions of the molecular
      elements. The success of the approach relies on the quality of the biological
      data. In this chapter, we discuss how a systems biology laboratory can apply
      microfluidics technology to acquire comprehensive, systematic, and quantitative
      data for their modeling needs.

PMID- 19399429
TI  - Ingeneue: a software tool to simulate and explore genetic regulatory networks.
AB  - Here I describe how to use Ingeneue, a software tool for constructing,
      simulating, and exploring models of gene regulatory networks. Ingeneue is an open
      source, extensible Java application that allows users to rapidly build ordinary
      differential equation models of a gene regulatory network without requiring
      extensive programming or mathematical skills. Models can be in a single cell or
      2D sheet of cells, and Ingeneue is well suited for simulating both oscillatory
      and pattern forming networks. Ingeneue provides features to allow rapid model
      construction and debugging, sophisticated visualization and statistical tools for
      model exploration, and a powerful framework for searching parameter space for
      desired behavior. This chapter provides an overview of the mathematical theory
      and operation of Ingeneue, and detailed walkthroughs demonstrating how to use the
      main features and how to construct networks in Ingeneue.

PMID- 19399430
TI  - Rule-based modeling of biochemical systems with BioNetGen.
AB  - Rule-based modeling involves the representation of molecules as structured
      objects and molecular interactions as rules for transforming the attributes of
      these objects. The approach is notable in that it allows one to systematically
      incorporate site-specific details about protein-protein interactions into a model
      for the dynamics of a signal-transduction system, but the method has other
      applications as well, such as following the fates of individual carbon atoms in
      metabolic reactions. The consequences of protein-protein interactions are
      difficult to specify and track with a conventional modeling approach because of
      the large number of protein phosphoforms and protein complexes that these
      interactions potentially generate. Here, we focus on how a rule-based model is
      specified in the BioNetGen language (BNGL) and how a model specification is
      analyzed using the BioNetGen software tool. We also discuss new developments in
      rule-based modeling that should enable the construction and analyses of
      comprehensive models for signal transduction pathways and similarly large-scale
      models for other biochemical systems.

PMID- 19399431
TI  - Modeling molecular regulatory networks with JigCell and PET.
AB  - We demonstrate how to model macromolecular regulatory networks with JigCell and
      the Parameter Estimation Toolkit (PET). These software tools are designed
      specifically to support the process typically used by systems biologists to model
      complex regulatory circuits. A detailed example illustrates how a model of the
      cell cycle in frog eggs is created and then refined through comparison of
      simulation output with experimental data. We show how parameter estimation tools
      automatically generate rate constants that fit a model to experimental data.

PMID- 19399432
TI  - Flux balance analysis: interrogating genome-scale metabolic networks.
AB  - Flux balance analysis (FBA) is a computational method to analyze reconstructions
      of biochemical networks. FBA requires the formulation of a biochemical network in
      a precise mathematical framework called a stoichiometric matrix. An objective
      function is defined (e.g., growth rate) toward which the system is assumed to be
      optimized. In this chapter, we present the methodology, theory, and common
      pitfalls of the application of FBA.

PMID- 19399433
TI  - Computational modeling of biochemical networks using COPASI.
AB  - Computational modeling and simulation of biochemical networks is at the core of
      systems biology and this includes many types of analyses that can aid
      understanding of how these systems work. COPASI is a generic software package for
      modeling and simulation of biochemical networks which provides many of these
      analyses in convenient ways that do not require the user to program or to have
      deep knowledge of the numerical algorithms. Here we provide a description of how
      these modeling techniques can be applied to biochemical models using COPASI. The
      focus is both on practical aspects of software usage as well as on the utility of
      these analyses in aiding biological understanding. Practical examples are
      described for steady-state and time-course simulations, stoichiometric analyses,
      parameter scanning, sensitivity analysis (including metabolic control analysis),
      global optimization, parameter estimation, and stochastic simulation. The
      examples used are all published models that are available in the BioModels
      database in SBML format.

PMID- 19399434
TI  - Systems biology of microbial communities.
AB  - Microbes exist naturally in a wide range of environments in communities where
      their interactions are significant, spanning the extremes of high acidity and
      high temperature environments to soil and the ocean. We present a practical
      discussion of three different approaches for modeling microbial communities: rate
      equations, individual-based modeling, and population dynamics. We illustrate the
      approaches with detailed examples. Each approach is best fit to different levels
      of system representation, and they have different needs for detailed biological
      input. Thus, this set of approaches is able to address the operation and function
      of microbial communities on a wide range of organizational levels.

PMID- 19399435
TI  - Dynamic knowledge representation using agent-based modeling: ontology
      instantiation and verification of conceptual models.
AB  - The sheer volume of biomedical research threatens to overwhelm the capacity of
      individuals to effectively process this information. Adding to this challenge is
      the multiscale nature of both biological systems and the research community as a
      whole. Given this volume and rate of generation of biomedical information, the
      research community must develop methods for robust representation of knowledge in
      order for individuals, and the community as a whole, to "know what they know."
      Despite increasing emphasis on "data-driven" research, the fact remains that
      researchers guide their research using intuitively constructed conceptual models
      derived from knowledge extracted from publications, knowledge that is generally
      qualitatively expressed using natural language. Agent-based modeling (ABM) is a
      computational modeling method that is suited to translating the knowledge
      expressed in biomedical texts into dynamic representations of the conceptual
      models generated by researchers. The hierarchical object-class orientation of ABM
      maps well to biomedical ontological structures, facilitating the translation of
      ontologies into instantiated models. Furthermore, ABM is suited to producing the
      nonintuitive behaviors that often "break" conceptual models. Verification in this
      context is focused at determining the plausibility of a particular conceptual
      model, and qualitative knowledge representation is often sufficient for this
      goal. Thus, utilized in this fashion, ABM can provide a powerful adjunct to other
      computational methods within the research process, as well as providing a
      metamodeling framework to enhance the evolution of biomedical ontologies.

PMID- 19399436
TI  - BioLogic: A mathematical modeling framework for immunologists.
AB  - The immune response to pathogens is a result of complex interactions among many
      cell types and a large number of molecular processes. As such it poses numerous
      challenges for modeling, simulation, and analysis. In this work we aim at
      addressing major issues regarding modeling of large biological systems with a
      special focus on the immune system. We address (1) the hierarchy in the system,
      from genes to organelles to cells to organs to organism, (2) the high variability
      due to experimentation, (3) the high variability among organisms, and (4) the
      need to bridge between immunologists/experimentalists and
      mathematicians/modelers. We provide an intuitive syntax to describe biological
      knowledge in terms of interactions (reactions) and objects (cells, organs, etc.)
      and illustrate how to use it in describing very complex systems. We describe the
      main elements of a simulation program that use that syntax to define models and
      to automatically simulate them. We restrict our discussion to modeling using
      logical network, although other modeling techniques, for example, differential
      equations and probabilistic/stochastic modeling, are also possible. Examples
      demonstrating the different features of the framework are given throughout the
      chapter.

PMID- 19399437
TI  - Multicell simulations of development and disease using the CompuCell3D simulation
      environment.
AB  - Mathematical modeling and computer simulation have become crucial to biological
      fields from genomics to ecology. However, multicell, tissue-level simulations of
      development and disease have lagged behind other areas because they are
      mathematically more complex and lack easy-to-use software tools that allow
      building and running in silico experiments without requiring in-depth knowledge
      of programming. This tutorial introduces Glazier-Graner-Hogeweg (GGH) multicell
      simulations and CompuCell3D, a simulation framework that allows users to build,
      test, and run GGH simulations.

PMID- 19399438
TI  - Model-based global analysis of heterogeneous experimental data using gfit.
AB  - Regression analysis is indispensible for quantitative understanding of biological
      systems and for developing accurate computational models. By applying regression
      analysis, one can validate models and quantify components of the system,
      including ones that cannot be observed directly. Global (simultaneous) analysis
      of all experimental data available for the system produces the most informative
      results. To quantify components of a complex system, the dataset needs to contain
      experiments of different types performed under a broad range of conditions.
      However, heterogeneity of such datasets complicates implementation of the global
      analysis. Computational models continuously evolve to include new knowledge and
      to account for novel experimental data, creating the demand for flexible and
      efficient analysis procedures. To address these problems, we have developed gfit
      software to globally analyze many types of experiments, to validate computational
      models, and to extract maximum information from the available experimental data.

PMID- 19399439
TI  - Location proteomics: systematic determination of protein subcellular location.
AB  - Proteomics seeks the systematic and comprehensive understanding of all aspects of
      proteins, and location proteomics is the relatively new subfield of proteomics
      concerned with the location of proteins within cells. This review provides a
      guide to the widening selection of methods for studying location proteomics and
      integrating the results into systems biology. Automated and objective methods for
      determining protein subcellular location have been described based on extracting
      numerical features from fluorescence microscope images and applying machine
      learning approaches to them. Systems to recognize all major protein subcellular
      location patterns in both two-dimensional and three-dimensional HeLa cell images
      with high accuracy (over 95% and 98%, respectively) have been built. The
      feasibility of objectively grouping proteins into subcellular location families,
      and in the process of discovering new subcellular patterns, has been demonstrated
      using cluster analysis of images from a library of randomly tagged protein
      clones. Generative models can be built to effectively capture and communicate the
      patterns in these families. While automated methods for high-resolution
      determination of subcellular location are now available, the task of applying
      these methods to all expressed proteins in many different cell types under many
      conditions represents a very significant challenge.

PMID- 19399440
TI  - A cell architecture modeling system based on quantitative ultrastructural
      characteristics.
AB  - The architecture of living cells is difficult to describe and communicate;
      therefore, realistic computer models may help their understanding. 3D models
      should correspond both to qualitative and quantitative experimental data and
      therefore should include specific authoring tools such as appropriate
      visualization and stereological measures. For this purpose we have developed a
      problem solving environment for stereology-based modeling (PSE-SBM), which is an
      automated system for quantitative modeling of cell architecture. The PSE-SBM
      meets the requirement to produce models that correspond in stereological and
      morphologic terms to real cells and their organelles. Instead of using standard
      interactive graphing tools, our approach relies on functional modeling. We have
      built a system of implicit functions and set operations, organized in a
      hierarchical tree structure, which describes individual cell organelles and their
      3D relations. Natural variability of size, shape, and position of organelles is
      achieved by random variation of the specific parameters within given limits. The
      resulting model is materialized by evaluation of these functions and is adjusted
      for a given set of specific parameters defined by the user. These principles are
      explained in detail, and modeling of segments of a muscle cell is used as an
      example to demonstrate the potential of the PSE-SBM for communication of
      architectural concepts and testing of structural hypotheses.

PMID- 19399441
TI  - Introduction: a practical guide to the systems approach in biology.
AB  - This essay provides an informal review of the modern systems-centric biological
      methodology for the practical researcher. The systems approach is defined, and a
      generic recipe for employing it in biomedical research is offered. General
      caveats are discussed that pertain to biological complexity, to explanation in
      molecular terms, and to bottom-up investigation. An outlook on the development of
      systems biology is also given.

PMID- 19399470
TI  - Potent anti-inflammatory effects of low-dose proteasome inhibition in the
      vascular system.
AB  - Proteasome inhibitors are considered to have anti-inflammatory therapeutic
      potential. However, recent reports addressing proteasome inhibition in the
      vascular system are controversial, ranging from beneficial anti-inflammatory and
      anti-oxidative effects to potentiation of inflammation and oxidative stress. This
      study was based on the hypothesis that the divergent effects might be a result of
      a differential and dose-dependent responsiveness of vascular cells to proteasome
      inhibitors. We tested whether low doses of proteasome inhibitors would favor anti
      inflammatory effects in vascular cells in vitro and in vivo. Human umbilical vein
      endothelial cells (HUVEC) were preincubated with proteasome inhibitors MG132 and
      MG262 at concentrations that did not affect cell viability during a 24-h
      treatment. Upon addition of tumor necrosis factor alpha (TNF-alpha) the induced
      expression of adhesion molecules and the adhesion of monocytic THP-1 cells to
      HUVECs was significantly lowered. However, nuclear translocation of NF-kappaB was
      only slightly diminished. Low-dose pretreatment with proteasome inhibitors
      decreased TNF-alpha-induced generation of reactive oxygen species in HUVEC.
      Bortezomib was administered at a dose of 50 microg/kg body weight to Dahl salt
      sensitive rats (DSSR) on high-salt diet. This low-dose proteasome inhibition led
      to decreased hypertension-induced oxidative stress and reduced expression of
      vascular cell adhesion molecule 1 (VCAM-1) in the aortae.

PMID- 19399471
TI  - An expression module of WIPF1-coexpressed genes identifies patients with
      favorable prognosis in three tumor types.
AB  - Wiskott-Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS
      is caused by mutations in the protein WASP which impair its interaction with the
      WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and
      to assess its use as a prognostic signature for colorectal cancer, glioma, and
      breast cancer patients. Two public colorectal cancer microarray data sets were
      used for discovery and validation of the WIPF1 co-expression module. Based on
      expression of the WIPF1 signature, we classified more than 400 additional tumors
      with microarray data from our own experiments or from publicly available data
      sets according to their WIPF1 signature expression. This allowed us to separate
      patient populations for colorectal cancers, breast cancers, and gliomas for which
      clinical characteristics like survival times and times to relapse were analyzed.
      Groups of colorectal cancer, breast cancer, and glioma patients with low
      expression of the WIPF1 co-expression module generally had a favorable prognosis.
      In addition, the majority of WIPF1 signature genes are individually correlated
      with disease outcome in different studies. Literature gene network analysis
      revealed that among WIPF1 co-expressed genes known direct transcriptional targets
      of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1
      signature genes is correlated with the profile of a proliferation signature. The
      WIPF1 signature is the first microarray-based prognostic expression signature
      primarily developed for colorectal cancer that is instrumental in other tumor
      types: low expression of the WIPF1 module is associated with better prognosis.

PMID- 19399472
TI  - Mapping of loci from Solanum lycopersicoides conferring resistance or
      susceptibility to Botrytis cinerea in tomato.
AB  - Cultivated tomato (Solanum lycopersicum, syn. Lycopersicon esculentum) is
      susceptible to the necrotrophic ascomycete and causal agent of gray mold,
      Botrytis cinerea. Resistance to this fungal pathogen is elevated in wild
      relatives of tomato, including Solanum lycopersicoides. An introgression line
      population (IL) containing chromosomal segments of S. lycopersicoides within the
      background of tomato cv. VF36 was used to screen the genome for foliar resistance
      and susceptibility to B. cinerea. Based on this screen, putative quantitative
      trait loci (QTL) were identified, five for resistance and two for susceptibility.
      Four resistance QTL decreased infection frequency while the fifth reduced lesion
      diameter. One susceptibility QTL increased infection frequency whereas the other
      increased lesion diameter. Overlapping chromosomal segments provided strong
      evidence for partial resistance on chromosomes 1 and 9 and for elevated
      susceptibility on chromosome 11. Segregation analysis confirmed the major
      resistance QTL on the long arm of chromosome 1 and susceptibility on chromosome
      11. Linkage of partial resistance to chromosome 9 could not be confirmed. The
      usefulness of these data for resistance breeding and for map-based cloning of
      foliar resistance to B. cinerea is discussed.

PMID- 19399473
TI  - Predictors of depressive symptoms in persons with diabetic peripheral neuropathy:
      a longitudinal study.
AB  - AIMS/HYPOTHESIS: The aim of the study was to determine whether diabetic
      peripheral neuropathy (DPN) is a risk factor for depressive symptoms and examine
      the potential mechanisms for this relationship. METHODS: This longitudinal study
      (9 and 18 month follow-up) of 338 DPN patients (mean age 61 years; 71% male; 73%
      type 2 diabetes) examined the temporal relationships between DPN severity (mean
      +/- SD; neuropathy disability score [NDS], 7.4 +/- 2.2; mean vibration perception
      threshold, 41.5 +/- 9.5 V), DPN somatic experiences (symptoms and foot
      ulceration), DPN psychosocial consequences (restrictions in activities of daily
      living [ADL] and social self-perception) and the Hospital Anxiety and Depression
      subscale measuring depressive symptoms (HADS-D; mean 4.9 +/- 3.7). RESULTS:
      Controlling for baseline HADS-D and demographic/disease variables, NDS at
      baseline significantly predicted increased HADS-D over 18 months. This
      association was mediated by baseline unsteadiness, which was significantly
      associated with increased HADS-D. Baseline ADL restrictions significantly
      predicted increased HADS-D and partly mediated the association between baseline
      unsteadiness and change in HADS-D. Increased pain, unsteadiness and ADL
      restrictions from baseline to 9 months each significantly predicted increased
      HADS-D over 18 months. Change in social self-perception from baseline to 9 months
      significantly predicted increased HADS-D and partly mediated the relationships of
      change in unsteadiness and ADL restrictions with change in HADS-D.
      CONCLUSIONS/INTERPRETATION: These results confirm that neuropathy is a risk
      factor for depressive symptoms because it generates pain and unsteadiness.
      Unsteadiness is the symptom with the strongest association with depression, and
      is linked to depressive symptoms by perceptions of diminished self-worth as a
      result of inability to perform social roles.

PMID- 19399474
TI  - Cuff-leak test for the diagnosis of upper airway obstruction in adults: a
      systematic review and meta-analysis.
AB  - PURPOSE: To evaluate, in adults, the diagnostic accuracy of the cuff-leak test
      for the diagnosis of upper airway obstruction secondary to laryngeal edema and
      for reintubation secondary to upper airway obstruction. METHODS: Systematic
      review without language restrictions based on electronic databases and manual
      review of the literature up to December 2008. When appropriate, a random-effects
      meta-analysis and meta-regression (Moses' method) were performed. RESULTS: Upper
      airway obstruction was the outcome in nine studies with an overall incidence of
      6.9%. There was significant heterogeneity among studies. The pooled sensitivity
      was 0.56 (95% confidence interval: 0.48-0.63), the specificity was 0.92 (95% CI:
      0.90-0.93), the positive likelihood ratio was 5.90 (95% CI: 4.00-8.69), the
      negative likelihood ratio was 0.48 (95% CI: 0.33-0.72), and the diagnostic odds
      ratio was 18.78 (95% CI: 7.36-47.92). The area under the curve of the summary
      receiver-operator characteristic (SROC) was 0.92 (95% CI: 0.89-0.94). Only three
      studies have evaluated the accuracy of the cuff-leak test for reintubation
      secondary to upper airway obstruction. Overall incidence was 7%. The pooled
      sensitivity was 0.63 (95% CI: 0.38-0.84), the specificity was 0.86 (95% CI: 0.81
      0.90), the positive likelihood ratio was 4.04 (95% CI: 2.21-7.40), the negative
      likelihood ratio was 0.46 (95% CI: 0.26-0.82), and the diagnostic odds ratio was
      10.37 (95% CI: 3.70-29.13). CONCLUSIONS: A positive cuff-leak test (absence of
      leak) should alert the clinician of a high risk of upper airway obstruction.

PMID- 19399475
TI  - Double-bundle PCL reconstruction using tibial double cross-pin fixation.
AB  - The purpose of this study was to assess the clinical results of arthroscopic
      double-bundle posterior cruciate ligament (PCL) reconstruction using double cross
      pin fixation on the tibial side. Twenty-two patients who underwent PCL
      reconstruction using an Achilles tendon allograft with double cross-pins for
      tibial fixation were evaluated. There were 19 men and 3 women with mean age 36
      years (range 18-59), and the average follow-up period was 33 months (range 24
      60). Preoperative and postoperative knee functions were evaluated in all patients
      using Lysholm knee scores, the 2000 International Knee Documentation Committee
      (IKDC) grades, and Tegner activity scores. Median Lysholm knee scores were 64 (50
      75) preoperatively and 88 (82-96), 89.9 +/- 6.5 postoperatively (P < 0.001).
      Median side-to-side differences, determined using Telos stress radiographs, were
      11 mm (8-14) preoperatively, and 3 mm (1-7) at final follow-up visits (P < 0.01).
      According to KT-2000 arthrometer measurements, mean side-to-side differences were
      11 mm (8-13) preoperatively and 3 mm (1-6, P < 0.01) at final follow-up visits (P
      < 0.01). Preoperatively the 2000 IKDC evaluation system rated all patients as
      abnormal or severely abnormal (C or D), and at final follow-up visits, 20
      patients (88%) were rated as normal or nearly normal (A or B) and 2 patients
      (12%) were rated as abnormal (C). Median preinjury and preoperative Tegner scores
      were 7 (range 5-9) and 3 (range 2-5), respectively, and the mean postoperative
      Tegner score was 6 (range 3-9). There were no intraoperative or postoperative
      complications. Our study shows that arthroscopic double-bundle PCL reconstruction
      using an Achilles allograft with double cross-pins for tibial fixation provides
      satisfactory clinical results given a mean follow-up of 33 months. We believe
      that this method provides a reliable alternative technique of PCL reconstruction.

PMID- 19399476
TI  - Avoiding pitfalls in anatomic ACL reconstruction.
AB  - As interest in double-bundle anterior cruciate ligament (ACL) reconstruction
      grows, we continue to refine our technique to perform the most anatomic
      reconstruction possible. Our experience has brought to our attention the
      potential mistakes that should be avoided when performing an anatomic double
      bundle ACL reconstruction. These mistakes include (1) failure to visualize the
      femoral insertion completely, (2) use of the clock face to reference femoral
      tunnel positioning, (3) nonanatomic tunnel placement leading to graft
      impingement, (4) mismatching tibial and femoral tunnels, and (5) failure to
      restore the native tension pattern of the ACL. It is also important to recognize
      that a double-bundle ACL reconstruction is not necessarily equivalent to an
      anatomic double-bundle reconstruction. This article reviews potential mistakes in
      DB ACL reconstruction and describes our way of avoiding them.

PMID- 19399477
TI  - Do physical diagnostic tests accurately detect meniscal tears?
AB  - Numerous physical tests have been described but their diagnostic accuracy is
      often questioned. Karachalios et al. described the new 'Thessaly test' and
      concluded that it could be safely used as a first line screening test for the
      selection of patients who need arthroscopic meniscal surgery. Our objective was
      to study the role of physical diagnostic tests in screening for meniscal tears
      and to validate the diagnostic accuracy of the Thessaly test. We examined 109
      patients (80 male, 29 female; average age: 39 years; range: 16-56) who were
      presented with a history suggestive of a meniscal tear. Joint line tenderness,
      McMurray's test, and the Thessaly test were assessed by an independent
      investigator blinded to any imaging data in all patients. MRI and subsequent
      arthroscopy results were then collated. Our study showed a much lower diagnostic
      accuracy for the Thessaly test (61% for medial meniscus and 80% for lateral
      meniscus). It is comparable to McMurray's test (57% for medial meniscus and 77%
      for lateral meniscus). The Joint line tenderness test has a far superior
      diagnostic accuracy (81% for medial meniscus and 90% for lateral meniscus).
      However, combining the joint line tenderness test with McMurray's test or the
      joint line tenderness test with Thessaly test further increased the accuracy of
      physical diagnosis of meniscal tears. Magnetic resonance imaging (MRI) detected
      96% of meniscal tears. Physical tests may not always be diagnostic of meniscal
      tears. MRI and arthroscopy may be essential in dubious clinical presentations and
      especially where more than one pathology is suspected. Our study showed that the
      Thessaly test in isolation was not useful for the detection of meniscal tears but
      it helps to increase diagnostic certainty when combined with other standard
      tests.

PMID- 19399478
TI  - One-stage anatomic double-bundle anterior and posterior cruciate ligament
      reconstruction using the autogenous hamstring tendons.
AB  - This is the first report of an anatomic double-bundle ACL and PCL reconstruction
      procedure with the autogenous hamstring tendons. We prepare two pairs of the
      doubled tendon grafts, to which a polyester tape and an Endobutton-CL are
      attached using our original technique at the tibial and femoral ends,
      respectively. Under arthroscopic and fluoroscopic observations, two tibial
      tunnels for PCL reconstruction are created so that they pass through the
      posteromedial and anterolateral bundle attachments, respectively. Then, we create
      two tibial tunnels for anatomic double-bundle ACL reconstruction so that each
      tunnel axis is aimed at a targeted point on the femoral condyle. Using the
      outside-in technique, two femoral tunnels for PCL reconstruction are created so
      that the tunnel outlets are located at the center of the anterolateral and
      posteromedial bundle attachments. Then, two femoral tunnels for anatomic double
      bundle ACL reconstruction are created with the trans-tibial tunnel technique.
      After the two grafts have been placed for PCL reconstruction, the two grafts are
      placed for ACL reconstruction. After all the femoral graft ends are fixed, the
      knee joint is reduced to the full extension position, and then, the four tibial
      tape portions are simultaneously fixed with the turn-buckle stapling technique.

PMID- 19399479
TI  - Cartilage defects of the femoral trochlea.
AB  - Despite improvements in the ability to detect articular cartilage defects of the
      trochlea, determining the significance of these lesions remains difficult.
      Physical examination and history taking remain the best way to estimate the
      clinical impact of these lesions. Debridement and/or microfracture are often
      initial surgical interventions; these procedures can be expected to provide
      functional improvement in over 50%, but studies suggest that the amount of
      improvement deteriorates within 3 years. While initial reports on ACI and
      osteochondral allografts in the treatment of trochlear defects appear to be more
      promising solutions, long-term follow-up studies are lacking. Similarly, the
      effect of tibial tubercle osteotomy combined with cartilage restoration
      techniques remains unresolved. Nonetheless, based on the limited available
      evidence, ACI or osteochondral allografts combined with a tibial tubercle
      osteotomy when appropriate have provided the most durable treatment for these
      difficult-to-treat lesions.

PMID- 19399480
TI  - Arthroscopic fixation for a malunited greater tuberosity fracture using the
      suture-bridge technique: technical report and literature review.
AB  - Greater tuberosity of the humerus malunion is relatively uncommon, and open
      techniques are the treatment of choice in most cases. Recent advances in
      arthroscopic techniques for treatment of greater tuberosity fractures have
      produced promising results. The use of arthroscopic techniques for the treatment
      of proximal humerus malunion, however, has been reported only rarely in the
      literature. This case report describes the malunited greater tuberosity fracture
      treated arthroscopically using the suture-bridge technique.

PMID- 19399481
TI  - Involvement of sensory nerves and TRPV1 receptors in the rat airway inflammatory
      response to two environment pollutants: diesel exhaust particles (DEP) and 1,2
      naphthoquinone (1,2-NQ).
AB  - The environmental chemical 1,2-naphthoquinone (1,2-NQ) is implicated in the
      exacerbation of airways diseases induced by exposure to diesel exhaust particles
      (DEP), which involves a neurogenic-mediated mechanism. Plasma extravasation in
      trachea, main bronchus and lung was measured as the local (125)I-bovine albumin
      accumulation. RT-PCR quantification of TRPV1 and tachykinin (NK(1) and NK(2))
      receptor gene expression were investigated in main bronchus. Intratracheal
      injection of DEP (1 and 5 mg/kg) or 1,2-NQ (35 and 100 nmol/kg) caused oedema in
      trachea and bronchus. 1,2-NQ markedly increased the DEP-induced responses in the
      rat airways in an additive rather than synergistic manner. This effect that was
      significantly reduced by L-732,138, an NK(1) receptor antagonist, and in a lesser
      extent by SR48968, an NK(2) antagonist. Neonatal capsaicin treatment also
      markedly reduced DEP and 1,2-NQ-induced oedema. Exposure to pollutants increased
      the TRPV1, NK(1) and NK(2) receptors gene expression in bronchus, an effect was
      partially suppressed by capsaicin treatment. In conclusion, our results are
      consistent with the hypothesis that DEP-induced airways oedema is highly
      influenced by increased ambient levels of 1,2-NQ and takes place by neurogenic
      mechanisms involving up-regulation of TRPV1 and tachykinin receptors.

PMID- 19399482
TI  - Rapid amplification of genetically modified organisms using a circular ferrofluid
      driven PCR microchip.
AB  - The use of genetically modified organisms (GMOs) as food and in food products is
      becoming more and more widespread. Polymerase chain reaction (PCR) technology is
      extensively used for the detection of GMOs in food products in order to verify
      compliance with labeling requirements. In this paper, we present a novel close
      loop ferrofluid-driven PCR microchip for rapid amplification of GMOs. The
      microchip was fabricated in polymethyl methacrylate by CO2 laser ablation and was
      integrated with three temperature zones. PCR solution was contained in a circular
      closed microchannel and was driven by magnetic force generated by an external
      magnet through a small oil-based ferrofluid plug. Successful amplification of
      genetically modified soya and maize were achieved in less than 13 min. This PCR
      microchip combines advantages of cycling flexibility and quick temperature
      transitions associated with two existing microchip PCR techniques, and it
      provides a cost saving and less time-consuming way to conduct preliminary
      screening of GMOs.

PMID- 19399483
TI  - Novel approach for interlaboratory transfer of real-time PCR methods: detecting
      bovine meat and bone meal in feed.
AB  - The availability of robust methods for the species-specific detection of meat and
      bone meal (MBM) in compound feedingstuffs is an important prerequisite to enforce
      current and upcoming European legislation on the use of processed animal proteins
      in animal nutrition. Among possible methods, those based on DNA turned out to be
      a reliable tool for this aim, since DNA is a quite thermostable molecule able to
      resist severe heat treatments applied in the manufacturing of animal meals. The
      application of such methods by control laboratories implies that the method has
      been validated including an assessment of its robustness. Successful
      transferability between laboratories is considered an important robustness
      criterion of the method. However, corresponding guidelines regarding the design
      of such a study relevant to this field are missing. Here, we demonstrate the
      feasibility of an alternative concept that was applied to check for the
      transferability of a qualitative assay for the detection of banned MBM in
      feedingstuffs at trace level based on real-time PCR. The concept was based on an
      experimental nested design applying analysis of variance (ANOVA) that was
      conducted independently in two laboratories and which allows for establishing
      major factors influencing the result of analysis. Statistical assessment of the
      results confirmed the importance of the DNA extraction/purification step
      utilised, whereas the PCR step turned out to be a minor factor regarding the
      overall variability of the results. Furthermore, blind samples comprised of
      compound feed adulterated with MBM at 0.1% and blank compound feed were correctly
      classified as "positive" or "negative" samples, thus confirming fitness of
      purpose for the method. This approach can be of interest for other research
      groups working in the development of real-time PCR methods and in their use by
      control laboratories.

PMID- 19399485
TI  - Drug interactions between inhaled corticosteroids and enzymatic inhibitors.

PMID- 19399484
TI  - Converting cold into pain.
AB  - Cold temperature can evoke a wide spectrum of perceptual sensations that range
      from freshness to unpleasant cold or overt pain. In mammals, the detection of
      cold temperature is accomplished by the activation of different subsets of
      sensory terminals innervating the skin and mucosae. Direct recordings of corneal
      nerve endings, combined with studies of thermoreceptive neurons in culture, have
      allowed the characterization of ionic mechanisms involved in cold temperature
      sensing. In recent years, major progress has also taken place in the
      identification and operation of thermally gated ion channels, especially of the
      transient receptor potential (TRP) family. However, it is still uncertain how
      individual sensory endings can be activated with different thermal thresholds. In
      this review, we have considered the known properties of cold-sensitive receptors
      and their transduction mechanisms and related them to the sensations they evoke.
      We analyzed the evidence linking specific ion channels to the activation of
      particular sets of afferent fibers. In our view, cold thermotransduction is
      complex and involves the concerted operation of several ion channels. Excitatory
      effects of cationic channels (e.g., TRPs) balance their activity with several
      excitability brakes (e.g., potassium channels), leading to tunable levels of
      sensory thresholds and activity. Alteration in this fine balance may result in
      altered cold sensitivity, a frequent symptom in patients with peripheral nerve
      injury.

PMID- 19399486
TI  - UEMS Division of Neuroradiology--a new development for European neuroradiology.

PMID- 19399488
TI  - Comparing three-dimensional volume-rendered CT images with fibreoptic
      tracheobronchoscopy in the evaluation of airway compression caused by tuberculous
      lymphadenopathy in children.
AB  - BACKGROUND: Lymphobronchial tuberculosis (TB) causes airway compression in 38% of
      patients. The airway obstruction is conventionally assessed with fibreoptic
      tracheobronchoscopy (FTB). Multidetector-row spiral computed tomography (MDCT)
      with three-dimensional volume rendering (3-D VR) has significantly improved the
      imaging of the airways. No previous studies have assessed the accuracy of 3-D VR
      in determining the degree of airway compression in children due to TB
      lymphadenopathy. OBJECTIVE: To compare 3-D VR CT to FTB for the assessment of
      airway compression due to TB lymphadenopathy in children. MATERIALS AND METHODS:
      Included in the study were 26 children presenting with symptoms of airway
      compression caused by pulmonary TB. MDCT of the chest and FTB were performed in
      all patients. Retrospective 3-D VR reconstruction of the major airways was
      performed from the original CT raw data and used to evaluate the tracheobronchial
      tree for site and degree of airway compression and then compared to the FTB
      findings. FTB was used as the reference standard RESULTS: By FTB 87 sites of
      airway compression were identified. Using the 3-D VR technique, 138 sites of
      airway compression were identified, of which 78 (90%) matched with the sites
      identified by FTB. The sensitivity and specificity of 3-D VR when compared with
      that of FTB was 92% and 85%, respectively. In four patients (15%), severe
      narrowing of the bronchus intermedius made FTB evaluation of the right middle and
      right lower lobe bronchi impossible. VR demonstrated significant distal
      obstruction in three of these four patients CONCLUSION: 3-D VR demonstrates a
      very good correlation with FTB in determining airway compression caused by TB
      lymphadenopathy in children. In combination with FTB, 3-D VR adds confidence to
      the bronchoscopy findings and complements FTB by adding additional information on
      the status of the airway distal to severe obstructions unreachable by FTB.

PMID- 19399489
TI  - Accidental aspiration of barium sulphate in an infant.

PMID- 19399490
TI  - Nonaccidental trauma: clinical aspects and epidemiology of child abuse.

PMID- 19399491
TI  - Nonaccidental trauma: clinical aspects and epidemiology of child abuse.

PMID- 19399492
TI  - Erythrocyte orientational and cell volume effects on NMR q-space analysis:
      simulations of restricted diffusion.
AB  - Pulsed field-gradient spin echo nuclear magnetic resonance spectroscopy of water
      diffusing in erythrocytes leads to diffusion interference and diffraction
      effects, which are visualised in q-space plots of signal intensity versus the
      magnitude of the spatial wave-number vector q. Interpretation of the features of
      these q-space plots has been aided by Monte Carlo random walk simulations of
      diffusion in lattices of virtual erythrocytes. Here, the effect of varying the
      orientation of the cells with respect to the direction in which diffusion is
      measured, on the appearance of q-space plots, was investigated, together with the
      effect of changing the cell volume. We show that these changes are reflected in
      the appearance of the plots in a way that is diagnostic of the microscopic
      geometry of the sample.

PMID- 19399494
TI  - Optimization of enzymatic hydrolysis and ethanol fermentation from AFEX-treated
      rice straw.
AB  - An abundant agricultural residue, rice straw (RS) was pretreated using ammonia
      fiber expansion (AFEX) process with less than 3% sugar loss. Along with
      commercial cellulase (Spezyme CP) at 15 filter paper unit/g of glucan, the
      addition of Multifect Xylanase at 2.67 mg protein/g glucan and Multifect
      Pectinase at 3.65 mg protein/g glucan was optimized to greatly increase sugar
      conversion of AFEX-treated RS. During enzymatic hydrolysis even at 6% glucan
      loading (equivalent to 17.8% solid loading), about 80.6% of glucan and 89.6% of
      xylan conversions (including monomeric and oligomeric sugars) were achieved.
      However, oligomeric glucose and xylose accounted for 12.3% of the total glucose
      and 37.0% of the total xylose, respectively. Comparison among the three
      ethanologenic strains revealed Saccharomyces cerevisiae 424A(LNH-ST) to be a
      promising candidate for RS hydrolysate with maximum ethanol metabolic yield of
      95.3% and ethanol volumetric productivity of 0.26 g/L/h. The final concentration
      of ethanol at 37.0 g/L was obtained by S. cerevisiae 424A(LNH-ST) even with low
      cell density inoculum. A biorefinery combining AFEX pretreatment with S.
      cerevisiae 424A(LNH-ST) in separate hydrolysis and fermentation could achieve
      175.6 g EtOH/kg untreated rice straw at low initial cell density (0.28 g dw/L)
      without washing pretreated biomass, detoxification, or nutrient supplementation.

PMID- 19399493
TI  - Ubiquitous SPRY domains and their role in the skeletal type ryanodine receptor.
AB  - We recently identified the second of three SPRY domains in the skeletal muscle
      ryanodine receptor type 1 (RyR1) as a potential binding partner in the RyR1 ion
      channel for the recombinant II-III loop of the skeletal muscle dihydropyridine
      receptor, for a scorpion toxin, Imperatoxin A and for an interdomain interaction
      within RyR1. SPRY domains are structural domains that were first described in the
      fungal Dictyostelium discoideum tyrosine kinase spore lysis A and all three
      isoforms of the mammalian ryanodine receptor (RyR). Our studies are the first to
      assign a function to any of the three SPRY domains in the RyR. However, in other
      systems SPRY domains provide binding sites for regulatory proteins or
      intramolecular binding sites that maintain the structural integrity of a protein.
      In this article, we review the general characteristics of a range of SPRY domains
      and discuss evidence that the SPRY2 domain in RyR1 supports interactions with
      binding partners that contain a structural surface of aligned basic residues.

PMID- 19399495
TI  - Citric acid wastewater as electron donor for biological sulfate reduction.
AB  - Citrate-containing wastewater is used as electron donor for sulfate reduction in
      a biological treatment plant for the removal of sulfate. The pathway of citrate
      conversion coupled to sulfate reduction and the microorganisms involved were
      investigated. Citrate was not a direct electron donor for the sulfate-reducing
      bacteria. Instead, citrate was fermented to mainly acetate and formate. These
      fermentation products served as electron donors for the sulfate-reducing
      bacteria. Sulfate reduction activities of the reactor biomass with acetate and
      formate were sufficiently high to explain the sulfate reduction rates that are
      required for the process. Two citrate-fermenting bacteria were isolated. Strain
      R210 was closest related to Trichococcus pasteurii (99.5% ribosomal RNA (rRNA)
      gene sequence similarity). The closest relative of strain S101 was Veillonella
      montepellierensis with an rRNA gene sequence similarity of 96.7%. Both strains
      had a complementary substrate range.

PMID- 19399496
TI  - Characterization of a novel cry8 gene specific to Melolonthidae pests:
      Holotrichia oblita and Holotrichia parallela.
AB  - A new polymerase chain reaction-restriction fragment length polymorphism method
      for the identification of cry8-type genes from Bacillus thuringiensis has been
      established by designing a pair of new universal primers. By this method, a novel
      gene, cry8Ga1, encoding a polypeptide of 1,157 amino acids with a deduced
      molecular mass of 131.2 kDa was identified and cloned from B. thuringiensis HBF
      18. Recombinant B. thuringiensis strain HD8G, harboring cry8Ga1, has insecticidal
      activity against larvae of Melolonthidae pests: Holotrichia oblita and
      Holotrichia parallela. This is the first report of a Cry toxin that has
      insecticidal activity to Melolonthidae pest H. oblita.

PMID- 19399497
TI  - Use of cyclodextrin and its derivatives for increased transformation efficiency
      of competent bacterial cells.
AB  - Methodologies for introduction of DNA into cells are essential in molecular
      genetics and vital for applications such as genetic engineering and gene therapy.
      The use of cyclodextrins (CyDs) for increased efficiency of introducing DNA into
      eukaryotic cells (transfection) has been reported, but CyDs' effect on the
      introduction of DNA into bacterial cells (transformation) is unknown. Here, we
      have investigated the potential of using CyDs in the transformation of chemically
      competent in-house, commercially available, and, on non-competent bacterial
      cells, with plasmid DNA of two different sizes. Possible interactions between
      CyDs and DNA were studied with nuclear magnetic resonance (NMR) spectroscopy. The
      presence of CyDs resulted in an up to fourfold increment of the transformation
      rate for in-house cells, with beta-CyD and derivates giving the strongest effect.
      For commercial cells and transformation with megaplasmids, a more moderate effect
      around 1.4-fold was obtained. However, CyDs have little or no effect on DNA
      uptake by noncompetent cells. Results obtained from NMR spectroscopy show no
      interactions between CyDs and DNA-like molecules, which indicated that the CyDs'
      effect is related to the bacterial cell wall.

PMID- 19399498
TI  - Reply to: Determinants of (131)I radiation dose to thyroid follicular cells.

PMID- 19399499
TI  - Relationship between joint gap difference and range of motion in total knee
      arthroplasty: a prospective randomised study between different platforms.
AB  - The objective of this study was to investigate the range of motion (ROM) of the
      knee before and four years after total knee arthroplasty (TKA) with a mobile or
      fixed type of platform and to prospectively evaluate whether there was a
      difference in ligament balance between the platform types. The subjects were 68
      patients involving 76 joints. The mobile type was used in 31 joints and fixed
      type in 45 joints by employing a prospective randomised method. The passive
      maximum ROM was measured using a goniometer before and four years after surgery.
      Also, the intraoperative knee ligament balance was measured. The postoperative
      extension ROM was significantly improved after TKA using a mobile bearing type
      compared with that employing a fixed bearing type. In TKA using the former, the
      intraoperative gap difference was not related to the postoperative flexion angle
      of the knee. However, they were related in TKA using a fixed bearing type, with a
      positive correlation regarding the flexion gap.

PMID- 19399500
TI  - Durable response to a single dose of Anti D in immune thrombocytopenic purpura in
      an adult with underlying human immunodeficiency viral infection.

PMID- 19399501
TI  - Biological reactive intermediates that mediate dacarbazine cytotoxicity.
AB  - PURPOSE: In the following, the cellular and molecular mechanism of cytotoxicity
      induced by prodrug dacarbazine toward the isolated rat hepatocytes was studied.
      METHOD: Accelerated cytotoxicity screening technique (ACMS) was used to perform
      this study. RESULT: Addition of dacarbazine to isolated rat hepatocytes resulted
      in reactive oxygen species (ROS) formation, and lysosomal membrane leakiness
      before hepatocyte lysis occurred. Hepatocyte ROS generation was inhibited by
      desferoxamine (a ferric chelator). Cytotoxicity was prevented by antioxidants or
      ROS scavengers (mannitol or dimethylsulfoxide), cytochorome P450 inhibitors
      (phenylimidazole, diphenyliodonium chloride, 4-methylpyrazole, and
      benzylimidazole). In addition to lysosomal damage, dacarbazine caused hepatocyte
      protease activation and cell proteolysis. CONCLUSION: Dacarbazine cytotoxicity is
      associated with ROS (H(2)O(2), O(2)(*-) ) generation. It is suggested that
      H(2)O(2) could cross the lysosomal membrane, react with lysosomal Fe(2+) to form
      hydroxyl radical (Haber-Weiss reaction) which is the major cause of lysosomal
      membrane leakiness, proteases, and other digestive enzymes' release and finally
      the cell death.

PMID- 19399502
TI  - Phase II and pharmacokinetic trial of rebeccamycin analog in advanced biliary
      cancers.
AB  - PURPOSE: Advanced cancers of the bile duct and gallbladder carry an ominous
      prognosis. Rebeccamycin analogue (RA) is a novel antitumor antibiotic where phase
      I trials suggested clinical efficacy in patients with biliary cancers. METHODS:
      The primary objective was to determine the response rate to RA in patients with
      advanced gallbladder and bile duct tumors. Secondary endpoints were survival and
      pharmacokinetic characterization. RA was given at a dose 165 mg/(m(2) day) x 5
      days every 3 weeks. RESULTS: Forty-six patients were enrolled. Nine patients were
      removed from study before their first planned imaging study for response. Two
      patients had partial responses and 16 had stable disease. On an intent-to-treat
      analysis the median survival was 6.3 months. A >20% drop in CA19.9 was seen in
      43% of patients with initial high levels. Grade 4 neutropenia and
      thrombocytopenia were seen in 35 and 5% of patients, respectively. Febrile
      neutropenia occurred in 16% of patients. The pharmacokinetic profile of this
      trial closely resembles those of prior phase I trials. Measured biliary
      concentrations of RA were as much as 100x greater than simultaneous plasma
      concentration. CONCLUSION: Although RA has a response rate of 5% in advanced
      biliary cancers, it is associated with significant numbers of patients
      experiencing prolonged stable disease. Biliary concentrations of RA are
      significantly greater than plasma concentrations.

PMID- 19399503
TI  - Higher genetic susceptibility to inflammation in mild disease activity of
      systemic lupus erythematosus.
AB  - In order to test the hypothesis that stratification of Mexican Modification of
      the Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI) simplifies
      the genetic study of SLE, we evaluated the genetic susceptibility to inflammation
      and defects in clearance of immune complexes among SLE patients in Taiwan. SLE
      phenotypes were stratified according to the MEX-SLEDAI scores into two subgroups
      (<or=10 and >10), and then according to renal disorder and neurological disorder,
      aiming to minimize any loss of power associated with disease heterogeneity. Upon
      stratification, IL1-beta polymorphism and LTA were significantly associated with
      SLE within the MEX-SLEDAI <or=10 subgroup. When SLE patients were classified into
      two subgroups with or without renal disorder to stratify the genetic study, we
      could find that the stratification with renal disorder could partially confirm
      the hypothesis that stratification of MEX-SLEDAI score simplifies the genetic
      study of complex diseases such as SLE. So we concluded that in the mild disease
      state of SLE, stratification of disease phenotypes, especially IL1-beta and LTA,
      according to MEX-SLEDAI scores could reveal new associations between candidate
      genes and disease activity index of SLE.

PMID- 19399504
TI  - MR imaging of the posterior hypophysis in children with tuberculous meningitis.
AB  - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) contributes
      to the morbidity and mortality in children with tuberculous meningitis (TBM). MRI
      assists in the early diagnosis of TBM and absence of the normal posterior
      pituitary bright spot (PPS) on T1-weighted MRI in TBM may indicate the functional
      integrity of the posterior hypophysis. The objective of this retrospective
      descriptive study of 22 children with TBM was to determine the prevalence of an
      absent PPS on T1-weighted MRI in children with TBM and its correlation with serum
      sodium levels (hyponatremia), severity of disease at presentation, and
      developmental outcome after 6 months. The prevalence of absent PPS in children
      with TBM was 55%. No significant correlation was found between the PPS and serum
      sodium status (p = 0.41) or severity of disease at presentation (p = 0.104).
      There was however a correlation between absent PPS and poorer developmental
      outcome at 6-month follow-up (p = 0.027).

PMID- 19399505
TI  - Diagnostic accuracy of contrast-enhanced MR angiography in severe carotid
      stenosis: meta-analysis with metaregression of different techniques.
AB  - Contrast-enhanced magnetic resonance angiography (CE-MRA) has become a well
      established noninvasive imaging method for the assessment of severe carotid
      stenosis (70-99% by NASCET criteria). However, CE-MRA is not a standardised
      technique, but encompasses different concurrent techniques. This review analyses
      possible differences. A bivariate random effects meta-analysis of 17 primary
      diagnostic accuracy studies confirmed a high pooled sensitivity of 94.3% and
      specificity of 93.0% for carotid CE-MRA in severe carotid stenosis. Sensitivity
      was fairly uniform among the studies, while specificity showed significant
      variation (I (2) = 73%). Metaregressions found significant differences for
      specificity with two covariates: specificity was higher when using not only
      maximum intensity projection (MIP) images, but also three-dimensional (3D) images
      (P = 0.01). Specificity was also higher with electronic images than with
      hardcopies (P = 0.02). The timing technique (bolus-timed, fluoroscopically
      triggered or time-resolved) did not result in any significant differences in
      diagnostic accuracy. Some nonsignificant trends were found for the percentages of
      severe carotid disease, acquisition time and voxel size. In conclusion, in CE-MRA
      of severe carotid stenosis the three major timing techniques yield comparably
      high diagnostic accuracy, electronic images are more specific than hardcopies,
      and 3D images should be used in addition to MIP images to increase the
      specificity.

PMID- 19399506
TI  - Ultrasound-guided percutaneous release of the annular pulley in trigger digit.
AB  - The purpose of this study was to describe and evaluate a new technique for
      ultrasound-guided percutaneous release of the annular pulley in trigger digit
      using a modified hypodermic needle. A total of 35 ultrasound-guided percutaneous
      releases were performed on 25 patients diagnosed and referred by hand surgeons in
      our institution over 16 months from October 2006. Inclusion criteria were as
      follows: adulthood, triggering present for at least 4 months, failure to respond
      to conservative management or steroid injections, no previous history of pulley
      release in the affected digit. Under ultrasound guidance, the affected pulley was
      released using a standard 19-gauge hypodermic needle bent at two points as the
      cutting device. Follow-up took place at 12 weeks and 6 months with improvement in
      triggering and clinically graded pain. At follow-up, no complications had
      occurred and all patients demonstrated improvement in their triggering, with
      complete resolution in 32 digits (91%), good improvement in 2 digits (6%) and
      some improvement in 1 digit (3%). This new technique uses a widely available and
      safe cutting device and is safe and can be used to provide definitive management
      for trigger finger, allowing the procedure to be performed in a variety of
      clinical settings.

PMID- 19399507
TI  - Consecutive cecum perforation due to incarcerated diaphragmatic hernia after
      liver surgery.

PMID- 19399509
TI  - [Stem cell therapy in multiple sclerosis: a clinical update].
AB  - Promising results in an animal model of multiple sclerosis (MS; experimental
      autoimmune encephalomyelitis, EAE) have shown that immunosuppression followed by
      allogeneic bone marrow transplantation has the potential to significantly
      ameliorate the spontaneous course of the disease. Since 1995, emerging data on
      autologous hematopoietic stem cell transplantation (AHSCT) has supported a
      benefit also in patients with multiple sclerosis. To date, results on
      approximately 500 cases have been consecutively reported by the European Group
      for Blood and Marrow Transplantation (EBMT). These reports have not only proved a
      favourable outcome for many patients but also provided the rationale for the
      currently ongoing controlled trials on AHSCT in MS. At present, results from the
      ASTIMS study in particular, a multicenter active-controlled phase II study, are
      awaited. However, a number of critical issues remain unresolved. Furthermore,
      with upcoming new treatment compounds that to some extent act via lymphoablative
      properties, it remains essential to better select those patients who might profit
      most from stem cell therapy based on a justifiable benefit-to-risk ratio.
      Although transplant related mortality has dropped to 1%, mortality combined with
      concerns about long-term safety remain critical issues in a primarily non-life
      threatening disease like MS.

PMID- 19399510
TI  - [Immunoablation followed by autologous stem cell transplantation in lupus: a
      clinical update].
AB  - Systemic lupus erythematosus (SLE) is a classic systemic autoimmune disease.
      Standard treatment consists of chronic therapy with antimalarials,
      glucocorticoids and immunosuppressive/cytotoxic drugs, which is associated with
      considerable side effects. In contrast, immunoablation of autoreactive
      immunologic memory followed by autologous stem cell transplantation (ASCT) has
      been the only regimen capable of inducing long-term remission of up to 10 years
      after cessation of immunosuppressive therapy, even in severely affected patients.
      Introduced in 1996, the procedure has since been performed in 147 patients with
      severe SLE refractory to standard treatment in clinical studies worldwide. Most
      of these patients achieved clinical long-term remission. However, SLE relapses
      and secondary autoimmune disorders have been reported. Transplant-related
      mortality occurred in 6% of the 147 cases, with a wide center effect (2-13%).
      Here we summarise the results published in the literature on immunoablation
      followed by ASCT in SLE and discuss future perspectives for optimising this
      therapeutic approach. It may be possible to improve the outcome and reduce the
      risks of treatment by identifying patients with a poor prognosis at an early
      stage, before irreversible organ damage has taken place.

PMID- 19399511
TI  - [Introduction to the topic: Stem cells and cell therapy].

PMID- 19399512
TI  - Unified staging system for Lewy body disorders: correlation with nigrostriatal
      degeneration, cognitive impairment and motor dysfunction.
AB  - The two current major staging systems in use for Lewy body disorders fail to
      classify up to 50% of subjects. Both systems do not allow for large numbers of
      subjects who have Lewy-type alpha-synucleinopathy (LTS) confined to the olfactory
      bulb or who pass through a limbic-predominant pathway that at least initially
      bypasses the brainstem. The results of the current study, based on examination of
      a standard set of ten brain regions from 417 subjects stained
      immunohistochemically for alpha-synuclein, suggest a new staging system that, in
      this study, allows for the classification of all subjects with Lewy body
      disorders. The autopsied subjects included elderly subjects with Parkinson's
      disease, dementia with Lewy bodies, incidental Lewy body disease and Alzheimer's
      disease with Lewy bodies, as well as comparison groups without Lewy bodies. All
      subjects were classifiable into one of the following stages: I. Olfactory Bulb
      Only; IIa Brainstem Predominant; IIb Limbic Predominant; III Brainstem and
      Limbic; IV Neocortical. Progression of subjects through these stages was
      accompanied by a generally stepwise worsening in terms of striatal tyrosine
      hydroxylase concentration, substantia nigra pigmented neuron loss score, Mini
      Mental State Examination score and score on the Unified Parkinson's Disease
      Rating Scale Part 3. Additionally, there were significant correlations between
      these measures and LTS density scores. It is suggested that the proposed staging
      system would improve on its predecessors by allowing classification of a much
      greater proportion of cases.

PMID- 19399513
TI  - Violence against children: further evidence suggesting a relationship between
      burns, scalds, and the additional injuries.
AB  - Up to 22 % of all child maltreatment cases involve non-accidental burns or
      scalds. In the time period of 2000 until 2007, 20 children with non-accidental
      burns and scalds in conjunction with other mechanisms of injury were examined at
      children's hospitals in Hamburg and at the Institute of Legal Medicine,
      University Medical Center Hamburg-Eppendorf, by experts in forensic medicine. The
      fact that these children presented with additional injuries due to blunt and
      sharp force and sometimes had signs of neglect emphasize the urgent need for a
      multidisciplinary cooperation between pediatricians and forensic medical experts
      to ensure the early identification and prevention of child maltreatment. A new
      approach for Germany, enforcing mandatory child well-being examinations is
      discussed.

PMID- 19399515
TI  - Activity-based differentiation of pathologists' workload in surgical pathology.
AB  - Adequate budget control in pathology practice requires accurate allocation of
      resources. Any changes in types and numbers of specimens handled or protocols
      used will directly affect the pathologists' workload and consequently the
      allocation of resources. The aim of the present study was to develop a model for
      measuring the pathologists' workload that can take into account the changes
      mentioned above. The diagnostic process was analyzed and broken up into separate
      activities. The time needed to perform these activities was measured. Based on
      linear regression analysis, for each activity, the time needed was calculated as
      a function of the number of slides or blocks involved. The total pathologists'
      time required for a range of specimens was calculated based on standard protocols
      and validated by comparing to actually measured workload. Cutting up, microscopic
      procedures and dictating turned out to be highly correlated to number of blocks
      and/or slides per specimen. Calculated workload per type of specimen was
      significantly correlated to the actually measured workload. Modeling
      pathologists' workload based on formulas that calculate workload per type of
      specimen as a function of the number of blocks and slides provides a basis for a
      comprehensive, yet flexible, activity-based costing system for pathology.

PMID- 19399514
TI  - The mammalian family of sterile 20p-like protein kinases.
AB  - Twenty-eight kinases found in mammalian genomes share similarity to the budding
      yeast kinase Ste20p. This review article examines the biological function of
      these mammalian Ste20 kinases. Some of them have conserved the Ste20p function of
      transducing extracellular signals to mitogen-activated kinases. Others affect ion
      transport, cell cycle, cytoskeleton organization, and program cell death. A
      number of molecular details involved in the activation of the kinases are
      discussed including autophosphorylation, substrate recognition, autoinhibition,
      dimerization, and substrate binding.

PMID- 19399517
TI  - The antiangiogenic effects of tyroservatide on animal models of hepatocellular
      carcinoma.
AB  - PURPOSE: To investigate the tumor inhibition and antiangiogenic effects of
      Tyroservatide (YSV, a small polypeptide composed of 3 amino acids. The chemical
      structure of YSV is l-tyrosine-l-serine-l-valine, molecular structure is
      C(17)H(25)N(3)O(6), and molecular weight is 367.40 Da) on human hepatocarcinoma
      SMMC-7721 transplanted tumors in nude mice. METHODS: The nude mice bearing
      xenografts of human hepatocarcinoma SMMC-7721 tumors were daily given
      intraperitoneal injection of YSV or saline as a control group after the tumor was
      implanted, total four groups with six mice in each. Calculating tumor volume and
      measuring tumor weight determined the extent of inhibition of xenografts. The
      microvessel density (MVD) of tumor tissue was measured by immunohistochemistry.
      Angiogenesis-related gene expression profile in tumor tissue was assayed by Oligo
      gene chip and checked by real-time PCR. The Serum concentration of selected
      factors was measured by ELISA. RESULT: YSV at 160, 320, or 640 microg/kg/day
      inhibited tumor growth in nude mice by 42.62, 60.66, and 27.59%, respectively,
      which were lower than that of control (P < 0.05). Immunohistochemical staining of
      the tumor tissue showed the decrease in MVD of tumor tissue after YSV injection.
      Comparing the 113 genes related with angiogenesis, we found that 18 genes showed
      the significant difference between the YSV groups and the control; vascular
      endothelial growth factor (VEGF) and interleukin-8 (IL-8) were the leading ones.
      The mRNA level as well as ELISA of VEGF and IL-8 in YSV group (320 microg/kg/day)
      were significantly decreased compared with the control (P < 0.05). CONCLUSION:
      YSV could inhibit the growth of human hepatocarcinoma SMMC-7721 tumor in nude
      mice, which might attribute to the inhibition of expression of angiogenesis
      related factors in mRNA and protein level.

PMID- 19399516
TI  - Experimental models of hepatocellular carcinoma: developments and evolution.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies in the
      world. The biological mechanisms of hepatocarcinogenesis and progression are
      poorly understood. Experimental models of HCC provide valuable tools to evaluate
      the risk factors, new treatment modalities and biologic characteristics. Under
      the constant evolution in model design and technology development, new
      experimental models continue to emerge, including spontaneous models, induced
      models, viral models, transplantable models, and genetically engineered models.
      These models are used as tools to investigate basic biological mechanisms of
      growth and differentiation, oncogene function, and as systems to test new
      diagnostic and therapeutic approaches. Each model has its own advantages and
      disadvantages. The progress in HCC model construction and studies are summarized
      in this review.

PMID- 19399518
TI  - Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1
      receptor blockers on survival in patients with advanced non-small-cell lung
      cancer undergoing first-line platinum-based chemotherapy.
AB  - PURPOSE: The renin-angiotensin system plays a crucial role in maintaining
      vascular homeostasis. Stimulation of angiotensin II type 1 receptors (AT1R) acts
      proangiogenically by increasing levels of vascular endothelial growth factor
      (VEGF). Consequently, cell culture experiments and animal studies have shown
      antiproliferative effects of AT1R blockers (ARB) and angiotensin I converting
      enzyme inhibitors (ACEI) in several malignancies. Until now, very limited
      clinical data for this antiangiogenic effect exists for combinations with
      antineoplastic chemotherapy. METHODS: A total of 287 patients with advanced non
      small-cell lung cancer undergoing first-line platinum-based chemotherapy were
      retrospectively analysed regarding long-term medication with ACEI and ARB as well
      as histological type, stage, performance status, gender, age, dose-intensity of
      chemotherapy and survival. RESULTS: Patients receiving either ACEI or ARB had a
      3.1 months longer median survival than non-recipients (11.7 vs. 8.6 months, HR
      0.56, P = 0.03). This survival advantage could not be attributed to other
      established risk-factors or dose intensity of chemotherapy. CONCLUSIONS: Addition
      of ACEI or ARB to platinum-based first-line chemotherapy may contribute to
      prolonged survival in patients with advanced lung cancer.

PMID- 19399519
TI  - Two new Isospora species from Brazilian tanager (Ramphocelus bresilius dorsalis)
      of South America.
AB  - Two new coccidian (Protozoa: Apicomplexa: Eimeriidae) species from the Brazilian
      tanager Ramphocelus bresilius dorsalis are reported in the current study.
      Isospora cadimi n. sp. oocysts are spheroidal to sub-spheroidal, 24.2 x 22.9
      microm, with a smooth and bi-layered wall, approximately 1.1 microm. Micropyle,
      oocyst residuum, and polar granule are absent. Sporocysts are broadly ovoidal,
      16.9 x 11.6 microm. Stieda and substieda bodies are present. Sporocyst residuum
      is present and sporozoites have refractile body and nucleus. Isospora navarroi n.
      sp. oocysts are spheroidal to sub-spheroidal, 21.4 x 20.6 microm, with a smooth
      and bi-layered wall, approximately 1.1 microm. Micropyle, oocyst residuum, and
      polar granule are absent. Sporocysts are ellipsoidal, 16.1 x 10.2 microm. Stieda
      and substieda bodies are present. Sporocyst residuum is present and sporozoites
      have a robust posterior refractile body.

PMID- 19399520
TI  - Experimental confirmation of multiple community states in a marine ecosystem.
AB  - Small changes in environmental conditions can unexpectedly tip an ecosystem from
      one community type to another, and these often irreversible shifts have been
      observed in semi-arid grasslands, freshwater lakes and ponds, coral reefs, and
      kelp forests. A commonly accepted explanation is that these ecosystems contain
      multiple stable points, but experimental tests confirming multiple stable states
      have proven elusive. Here we present a novel approach and show that mussel beds
      and rockweed stands are multiple stable states on intertidal shores in the Gulf
      of Maine, USA. Using broad-scale observational data and long-term data from
      experimental clearings, we show that the removal of rockweed by winter ice scour
      can tip persistent rockweed stands to mussel beds. The observational data were
      analyzed with Anderson's discriminant analysis of principal coordinates, which
      provided an objective function to separate mussel beds from rockweed stands. The
      function was then applied to 55 experimental plots, which had been established in
      rockweed stands in 1996. Based on 2005 data, all uncleared controls and all but
      one of the small clearings were classified as rockweed stands; 37% of the large
      clearings were classified as mussel beds. Our results address the establishment
      of mussels versus rockweeds and complement rather than refute the current
      paradigm that mussel beds and rockweed stands, once established, are maintained
      by site-specific differences in strong consumer control.

PMID- 19399521
TI  - The relevance of ants as seed rescuers of a primarily bird-dispersed tree in the
      Neotropical cerrado savanna.
AB  - The scale at which seed dispersal operates has many implications for the spatial
      patterns of plant recruitment and diversity. We investigated the effect of short-
      (ants) and long-distance (birds) seed dispersal of the fleshy-fruited melastome,
      Miconia rubiginosa, in the Brazilian savanna. We estimated the contribution of
      dispersal vectors to the removal of the fruit crop from the canopy (birds), and
      once seeds have reached the cerrado floor (ants) over two fruiting seasons. Birds
      (13 species) removed up to 23.7% of the fruit crop from the crown, but dropped a
      substantial proportion of fruits beneath the parent plant. Birds removed a
      greater proportion of fruits from trees producing large fruit crops, as predicted
      by the fruit crop size hypothesis. However, up to 18.9% of the fruit crop fell
      beneath the parent plant as ripe fruit. Most fallen fruits were removed by ants
      (seven genera), which are likely to play a relatively important role in terms of
      the quantity of seeds dispersed, especially for plants producing small fruit
      crops (a conceptual model is presented). Birds and ants did not influence seed
      germination, but they differ in terms of the spatial scale of dispersal and
      deposition patterns. Ants probably play an important role in the local population
      dynamics of Miconia, whereas birds are responsible for long-distance dispersal
      associated with the colonization of new patches and metapopulation dynamics. By
      removing seeds from bird droppings, ants may also reshape at a finer scale the
      seed rain generated by primary dispersers. Indeed, seedlings and saplings of
      Miconia are more frequently found around leaf-cutter ant nests than in control
      areas away from ant nests or around large Miconia trees. The quantitative
      component of dispersal effectiveness by ants acting as "rescuers" of seeds that
      fail to be dispersed, or fall under parent trees, is probably more important than
      currently recognized in other systems.

PMID- 19399522
TI  - Rituximab therapy in two children with autoimmune thrombotic thrombocytopenic
      purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare disease among pediatric
      patients, in whom it may be mistaken for hemolytic uremic syndrome (HUS) and
      idiopathic thrombocytopenic purpura (ITP). Familial forms are caused by mutations
      in the ADAMTS13 gene, whereas acquired forms may result from an inhibitory
      antibody directed against ADAMTS13, a metalloprotease that cleaves very large
      multimers of Von Willebrand factor (VWF), thereby preventing platelet aggregation
      in blood vessels. We report two cases of TTP. The first was a 15-year-old girl
      with her first episode of TTP that failed to respond after 10 days of
      plasmapheresis and was treated with rituximab; she has remained in remission at
      12 months of follow-up. The second was a 6-year-old boy with acquired relapsing
      TTP previously managed with plasmapheresis and prednisolone, who presented with a
      third relapse that was treated with plasmapheresis and rituximab; he remains in
      remission 17 months after treatment. Rituximab has been used by pediatricians for
      treating B cell malignancy, autoimmune diseases and antibody-mediated diseases,
      such as the Factor VIII inhibitors in hemophilia A, and may also have a promising
      role in children with acute refractory or chronic relapsing TTP.

PMID- 19399524
TI  - [What is the difference between patients with and without complex postoperative
      acute pain therapy?: An analysis of medical and economic characteristics].
AB  - BACKGROUND: Appropriate postoperative pain therapy is essential for an
      accelerated recovery. However, coding complex acute pain therapy (OPS 8-919) does
      not have any impact on hospital revenues. As medical and economic primary data
      related to this therapy are scarce, hospital data were analysed to identify
      differences between patients with and without acute pain therapy. MATERIAL AND
      METHODS: Two patient groups were generated out of an anonymized data set from 372
      acute care hospitals in 2005: The case group (G1) included 4,197 patients (OPS 8
      919 coded). The control group (G2) contained 61,181 patients (neither OPS 8-919
      nor 8-910 nor 8-911 coded). RESULTS: The analysis revealed that patients in G1
      had a prolonged mean length of hospital stay (2.5 days). The mean number of
      diagnoses per case was similar in both groups (G1:6.9, G2:6.6), whereas the mean
      number of procedures was higher in G1 (G1:8.2, G2:6.2). The difference in mean
      diagnosis-related group (DRG) revenue per case was about EUR 200 (G1:EUR 9,233,
      G2:EUR 9,030). CONCLUSION: To validate the results found in this analysis,
      further evaluations of these patient groups are essential. High-quality
      documentation and coding in hospitals are required for future studies.

PMID- 19399523
TI  - Non-drug-induced nephrotoxicity.
AB  - Several drugs and other compounds can induce acute and/or chronic nephrotoxicity.
      The goal of this study was to review clinical features of nephrotoxicity induced
      by 'atypical' or 'unconventional' agents, such as environmental agents (metals,
      minerals, animals), food agents (mushrooms, aristolochic acid, medicinal
      traditional herbals, dietary supplements, melamine), drugs, and other products
      (ethylene glycol). Nephrotoxicity varies according to local background, dependent
      on different food and cultural customs, as well as to differences in local fauna
      and flora. The incidence of such a phenomenon is not well known. Many different
      pathophysiological pathways are involved, and the spectrum of renal lesions is
      rather wide. 'Epidemic nephrotoxicity' may occur, as recently illustrated by the
      melamine epidemics in Chinese infants receiving powdered milk formulas; a rapid
      reaction to unusual increased frequency of acute kidney injury and
      nephrolithiasis in young children has led to a rapid analysis from international
      experts, with subsequent recommendations for diagnosis and care. Nephrotoxicity
      should be considered when there is any unexplained renal impairment, especially
      in children.

PMID- 19399525
TI  - [From wheelchair dependency to the ability to walk: lumbar sympathectomy as a
      treatment for complex regional pain syndrome].
AB  - A 34-year-old woman developed walking disability with wheelchair dependency for
      more than 2 years due to chronic regional pain syndrome type II (CRPS II) in the
      feet. After excluding neurological and vascular disease, lumbar sympathectomy was
      performed on both sides. Surgical treatment was uneventful, and the patient's
      symptoms dramatically improved after 2 months. She is now able to walk some 500
      m. This case illustrates the fact that surgical lumbar sympathectomy is an
      effective alternative or adjunct treatment even in fixed CRPS II.

PMID- 19399526
TI  - [Gender-specific risk factors for acute low back pain: starting points for target
      group-specific prevention].
AB  - BACKGROUND: Women complain about back pain more often than men, giving rise to
      the question of whether gender-specific risk profiles could be identified.
      METHODS: Secondary data analysis was done of the telephone health survey
      conducted by the Robert Koch Institute in 2003 (n=7,829). Bivariate (chi(2)) and
      gender-stratified multivariate tests were conducted (odds ratio, 95% confidence
      intervals). RESULTS: Women (28.5%) complained about acute low back pain
      significantly more often than men did (18%; p<0.001). The multivariate analysis
      found gender-specific risk estimates for the following factors: age, degenerative
      diseases of the joints, osteoporosis, depression, smoking, employment,
      municipality size, and impairment of daily work because of physical impairment.
      CONCLUSION: The present examination is an attempt to deduce factors to be taken
      into account for gender-specific care of patients with acute low back pain.
      Preventive measures and therapy approaches could be influenced by these findings.
      To adequately address the problem, future analyses should specifically include
      psychosocial factors.

PMID- 19399527
TI  - The life-sustaining treatments among cancer patients at end of life and the
      caregiver's experience and perspectives.
AB  - GOALS OF WORK: The goal of this study was to investigate the utilization of and
      attitudes toward life-sustaining treatments (LSTs) at the end of life. MATERIALS
      AND METHODS: We identified 4,042 families of cancer patients who had died at any
      of 17 hospitals in Korea during 2004. Among those, we analyzed the interviews
      provided by 1,592 (39.4%) primary caregivers. Only women who provided information
      in baseline and follow-up point could be included for internal comparison. MAIN
      RESULTS: Most caregivers did not discuss with their patient the option of
      utilizing the intensive care unit (ICU; 92.7%) or cardiopulmonary resuscitation
      (CPR; 93.7%) to prolong an ending life. Logistic regressions indicated that the
      ICU was more likely to be utilized when patients experienced an unexpected
      medical problem before dying, discussed the ICU with the family caregiver, or
      were low-educated. CPR was more likely to be used if the patient died within 6
      months of diagnosis or the family caregiver was <65 years old. Family caregivers
      more likely to use the ICU if placed in the same situation again were those whose
      patients had a higher monthly income or died within 6 months of diagnosis, low
      educated, or had utilized the ICU. CONCLUSIONS: Our findings underscore the
      importance of discussing LST with terminally ill patients based on adequate
      information.

PMID- 19399528
TI  - Evaluating beauty care provided by the hospital to women suffering from breast
      cancer: qualitative aspects.
AB  - GOALS OF WORK: Cancer patients are offered more and more access to beauty care
      during their stay in the hospital. This kind of intervention has not been
      evaluated yet. Primary objective of our research was to determine what type of
      evaluation strategy to be implemented (as a supportive care with quality of life
      and/or medical benefits; as a service providing immediate comfort); intermediate
      objective was to investigate in scientific terms (psychological, sociological)
      the experience of beauty care by patients. PATIENTS AND METHODS: Sixty patients
      (all users of beauty care provided by hospital, 58 female, most of them treated
      for breast cancer, two male, mean age 53 years) and 11 nurses and physicians,
      from four French cancer centres were included. We used direct observation and
      semi-structured interviews, conducted by a sociologist and a psychologist;
      different types of beauty care were concerned. RESULTS: All the interviewed
      patients were satisfied. Patients appreciated acquiring savoir-faire on how to
      use make-up and on personal image enhancement. Psychological and social well
      being benefits were mentioned. The beauty care was not alleged to be reducing the
      side effects of the treatments, but it had helped patients to accept or bear the
      burden of them. Providing care beyond that which is directly curative was
      appreciated by the patients as a sign that they were treated as a "whole" person.
      CONCLUSION: The survey brings valuable clues concerning beauty care experience by
      cancer patients; it suggests the relevance of quantitative evaluation of the
      immediate and long-term effects on the quality of life.

PMID- 19399529
TI  - Ostryopsis davidiana seedlings inoculated with ectomycorrhizal fungi facilitate
      formation of mycorrhizae on Pinus tabulaeformis seedlings.
AB  - Reforestation in China is important for reversing anthropogenic activities that
      degrade the environment. Pinus tabulaeformis is desired for these activities, but
      survival and growth of seedlings can be hampered by lack of ectomycorrhizae. When
      outplanted in association with Ostryopsis davidiana plants on reforestation
      sites, P. tabulaeformis seedlings become mycorrhizal and survival and growth are
      enhanced; without O. davidiana, pines often remain without mycorrhizae and
      performance is poorer. To better understand this relationship, we initiated an
      experiment using rhizoboxes that restricted root and tested the hypothesis that
      O. davidiana seedlings facilitated ectomycorrhizae formation on P. tabulaeformis
      seedlings through hyphal contact. We found that without O. davidiana seedlings,
      inocula of five indigenous ectomycorrhizal fungi were unable to grow and
      associate with P. tabulaeformis seedlings. Inocula placed alongside O. davidiana
      seedlings, however, resulted in enhanced growth and nutritional status of O.
      davidiana and P. tabulaeformis seedlings, and also altered rhizosphere pH and
      phosphatase activity. We speculate that these species form a common mycorrhizal
      network and this association enhances outplanting performance of P. tabulaeformis
      seedlings used for forest restoration.

PMID- 19399530
TI  - Minimally invasive spine stabilisation with long implants.
AB  - Originally aimed at treating degenerative syndromes of the lumbar spine,
      percutaneous minimally invasive posterior fixation is nowadays even more
      frequently used to treat some thoracolumbar fractures. According to the modern
      principles of saving segment of motion, a short implant (one level above and one
      level below the injured vertebra) is generally used to stabilise the injured
      spine. Although the authors generally use a short percutaneous fixation in
      treating thoracolumbar fractures with good results, they observed some cases in
      which the high fragmentation of the vertebral body and the presence of other
      associated diseases (co-morbidities) did not recommend the use of a short
      construct. The authors identified nine cases, in which a long implant (two levels
      above and two levels below the injured vertebra) was performed by a percutaneous
      minimally invasive approach. Seven patients (five males/two females) were
      affected by thoracolumbar fractures. T12 vertebra was involved in three cases, L1
      in two cases, T10 and L2 in one case, respectively. Two fractures were classified
      as type A 3.1, two as A 3.2, two as A 3.3 and one as B 2.3, according to Magerl.
      In the present series, there were also two patients affected by a severe
      osteolysis of the spine (T9 and T12) due to tumoral localisation. All patients
      operated on with long instrumentation had a good outcome with prompt and
      uneventful clinical recovery. At the 1-year follow-up, all patients except one,
      who died 11 months after the operation, did not show any radiologic signs of
      mobilisation or failure of the implant. Based on the results of the present
      series, the long percutaneous fixation seems to represent an effective and safe
      system to treat particular cases of vertebral lesions. In conclusion, the authors
      believe that a long implant might be an alternative surgical method compared to
      more aggressive or demanding procedures, which in a few patients could represent
      an overtreatment.

PMID- 19399531
TI  - Presence of NGF and its receptor TrkA in degenerative lumbar facet joint
      specimens.
AB  - In a preliminary study, the recurrent presence of nervous terminations was
      demonstrated with optical microscopy in several slides of degenerative lumbar
      facet joints and surrounding soft tissues. The purpose of this study was to prove
      the presence of NGF (nerve growth factor) and its receptor TrkA (tyrosine kinase
      receptor) with immunofluorescence. The peri/articular tissues were harvested from
      the lumbar facet joints of ten patients surgically treated for degenerative
      diseases. There were seven females (one bilateral) and two males whose mean age
      at surgery was 72 years (range, 67-80 years). The affected levels were L3-L4 in
      two cases and L4-L5 in seven cases (one bilateral). All specimens were fixed in
      formalin, dehydrated and enclosed in paraffin. From each specimen, four slides
      were obtained. Two slides were employed for the search of NGF: one was treated
      with specific antibodies and marked with FITC (fluorescein isothiocyanate
      conjugated), and the second slide was for control purposes. It was exposed to
      FITC, but without prior exposure to the specific antibody. The same procedure was
      repeated to obtain on two more slides, to repeat the search for Trka with
      specific antibodies. All the slides were finally studied on a fluoromicroscope.
      The analysis of these specimens revealed the presence of the neurotrophin (NGF)
      and its own receptor (TrkA) in all cases: the immunohistochemical reaction
      between the specimens and the specific antibodies marked with FITC was seen under
      fluoromicroscopy, but in none of the control cases treated with FITC only. NGF is
      released by mastocytes, fibroblasts and other cell types involved in the
      inflammatory processes. The level of peripheral NGF is increased in inflammatory
      processes, while the administration of exogenous NGF has a hyperalgesic effect on
      rats and produces muscular pain in humans. Furthermore, NGF produces
      hypersensitization to heat stimulation in humans and mammals in general. There is
      considerable evidence showing that the system constituted by the NGF and its high
      affinity receptor TrkA plays a fundamental role in the molecular processes
      underlying the main forms of "persistent" pain. This indicates a possible
      therapeutic area for the antibodies that could block the NGF/TrkA system, in
      order to modulate the frequency and the duration of the action potential of
      nociceptive neurons during chronic inflammation. This study demonstrated the
      presence of NGF and TrkA in specimens collected from degenerative facet joints,
      suggesting that specific molecules could be used in order to modulate chronic
      pain in patients with degenerative lumbar spine.

PMID- 19399532
TI  - Selective thoracic surgery in the Lenke type 1A: King III and King IV type
      curves.
AB  - Pedicle screw fixation enables enhanced three-dimensional correction of spinal
      deformities and effectively shortens the distal fusion level. However, the choice
      of distal fusion level is still controversial in single thoracic idiopathic
      scoliosis with the lumbar compensatory curve not crossing the middle line (Lenke
      type 1 with modifier A or King type III and IV curves).The authors
      retrospectively analyzed 31 patients treated by segmental pedicular
      instrumentation alone, affected by a single thoracic adolescent idiopathic
      scoliosis with a compensatory lumbar curve not crossing the midline (Lenke 1A),
      with an average age of 16.3 years (range 10-22 years). The patients with regard
      to the King classification were also assessed. A statistical analysis was
      performed to determine whether the two groups (King III, King IV) presented
      differences concerning the level of the stable vertebra (SV), end vertebra (EV),
      and neutral vertebra (NV) and were also analyzed the results at follow-up
      regarding the relationships between the SV, EV, and lowest instrumented vertebra
      (LIV). The statistical analysis showed a significant difference between the two
      curve types. In the King III type curve the SV, EV, and NV appeared to be more
      proximal than those of the King IV type curve and the segments between the SV,
      EV, and NV appeared to be reduced in King III curves compared with King IV
      curves. At a follow-up of 3.2 years (range 2.2-5) the thoracic curve showed a
      correction of 58.4% (from 62.3 degrees to 26.6 degrees ) and compensatory lumbar
      curve an average spontaneous correction of 52.4% (from 38.1 degrees to 18.1
      degrees ).The position of the LIV was shorter than the position of the SV in 30
      patients (97%) with an average "salvage" of 2.1 (from 1 to 4) distal fusion
      levels. Four cases (13%), all affected by a King IV type curve, presented at
      follow-up an unsatisfactory results due to an "adding on" phenomenon. The
      statistical analysis confirmed that this phenomenon was correlated with The King
      IV curve (P = 0.043; Chi-square test) and that the only predictive parameter for
      its onset was the LIV-SV difference (odds ratio = 0.093; with a confidence
      interval of 0.008-1): every time that in King IV curve type the LIV was three or
      more levels shorter than the stable vertebra at follow-up the "adding on"
      phenomenon was present. The authors conclude that Lenke's type 1 with modifier A
      includes two kinds of curves, King III and King IV and that the Lenke's type 2
      curves and King V with the lumbar curve not crossing the middle line have a
      similar behavior. Therefore, it is of authors' opinion that "the adding on
      phenomenon" could be prevented by more rigidly defining K. IV versus K. III
      curves. In Lenke's 1/2 A-K. IV/V type with the rotation of the first vertebra
      just below the thoracic lower EV in the same direction as the thoracic curve, and
      when SV and EV show more than two levels of difference, it is necessary to extend
      the lower fusion down to L2 or L3 (not more than two levels shorter than the SV).
      Whereas in Lenke's 1/2 A-K. III/V with the rotation of the first proximal
      vertebra of lumbar curve in the opposite direction to the thoracic apex and when
      SV and EV show not more than two level gap differences, the position of the
      lowest instrumented vertebra can be two or three levels shorter than the stable
      vertebra with satisfactory postoperative spinal balance. Therefore, the stable
      vertebra and the rotation of lumbar curve are considered to be a reliable guide
      for selecting the lower level of fusion.

PMID- 19399533
TI  - Minimally invasive percutaneous fixation in the treatment of thoracic and lumbar
      spine fractures.
AB  - We studied 51 patients with 64 fractures of the thoracolumbar and lumbar spine
      undergoing the surgical treatment by percutaneous trans-pedicular fixation and
      stabilization with minimally invasive technique. Patient follow-up ranged from 6
      to 28 months (mean 14.2 months) and the patients were assessed by clinical and
      radiographic evaluation. The results show that percutaneous trans-pedicular
      fixation and stabilization with minimally invasive technique is an adequate and
      satisfactory procedure to be used in specific type of the thoracolumbar and
      lumbar spine fractures.

PMID- 19399534
TI  - Relevance of the cranioaxial angle in the occipitocervical stabilization using an
      original construct: a retrospective study on 50 patients.
AB  - We present a retrospective study on a series composed of 50 patients, treated
      between 1992 and 2006, affected by pathologies of the craniocervical junction.
      All the patients were treated using an innovative procedure based on a cranial
      claw made up of low profile hooks, conceived by one of the authors. Advantages of
      this technique are, to our point of view, a higher resistance to cranial hooks
      dislodgment, when compared with screw fixation instrumentation, especially in
      pathological conditions, such as rheumatoid arthritis that leads to a qualitative
      deterioration of the bone stock and to the reduction of the occipital wall
      thickness. Occipitoaxial alignment was assessed radiographically using the
      McGregor line. We observed an improvement in the subjective evaluation of pain in
      all treated patients with a 46% improvement from the initial values. Moreover,
      patient stabilized with an occipitoaxial angle included in the physiological
      range showed better results either for the survival of the instrumentation or the
      onset of junctional pathology. Patients have been followed up afterwards and
      evaluated by the visual analogue scale for the assessment of pain and by the
      Nurick scale for the cases associated with myelopathy. We believe that cranial
      anchorage with a hook claw allows for an instrumentation provided with high
      stability, particularly useful in revision surgery and major instabilities. The
      study of the occipitoaxial angles showed that the better results and the long
      lasting stability of the implant are correlated to a fusion angle included in the
      physiological range.

PMID- 19399535
TI  - Novel concepts in the evaluation and treatment of high-dysplastic
      spondylolisthesis.
AB  - The classification system of spondylolisthesis proposed by Marchetti and
      Bartolozzi is the most practical regarding prognosis and treatment and includes
      the description of both low- and high-dysplastic developmental spondylolisthesis
      (HDDS). Unfortunately, it does not provide strict criteria on how to
      differentiate between these two subtypes. The accepted treatment for HDDS is
      surgical. However, there is no consensus on how to surgically stabilize this
      subtype of spondylolisthesis, and although the concept of reducing spinal
      deformity before fusion is attractive, the issue of surgical reduction versus in
      situ fusion remains controversial, especially for HDDS (Meyerding Grades III and
      IV). The purpose of this study was (1) to describe the severity index (SI) as a
      simple method that can be used in the identification of low-dysplastic
      developmental spondylolisthesis from HDDS allowing earlier surgical stabilization
      to prevent slip progression, (2) to provide guidelines for using the unstable
      zone for the inclusion of L4 in stabilization, and (3) to describe a surgical
      technique in the reduction and stabilization of this challenging surgical entity
      in an attempt to decrease the risk of iatrogenic L5 neurologic injury. The
      concepts of SI and unstable zone in the evaluation and treatment of HDDS are
      relatively new. In our study, patients with an SI value >20% were classified as
      having HDDS and surgical stabilization was offered. In addition, all vertebrae
      that were contained in the defined unstable zone were surgically instrumented and
      fused with attempts at anatomic reduction. This case series involved the
      retrospective radiological review of 25 consecutive patients surgically treated
      for HDDS between April 2000 and September 2004 by two senior surgeons. All 25
      patients had a minimum 3-year follow-up. Reduction of slip, lumbosacral kyphosis,
      sacral inclination, fusion rate, maintenance of reduction, and iatrogenic L5
      neurologic injury were evaluated. Twenty-two patients underwent a single-level L5
      S1 fusion. Three patients had extension of the L5-S1 fusion to include L4 because
      it fell into the unstable zone. Slip improved from 67.2 to 13.6%, focal L5-S1
      kyphosis improved from +17.5 degrees to -6.4 degrees . There were no
      pseudoarthroses and all patients had radiographic evidence of solid bony fusion
      at latest follow-up. To date, there have been no re-operations secondary to
      progression of deformity or loss of fixation. Two re-operations were performed,
      one for a superficial wound infection, the other for further laparoscopic
      decompression for continued L5 nerve root symptoms after the index surgery. One
      patient developed an iatrogenic L5 radiculopathy with dysaesthesiae 3 days
      postoperatively which completely resolved over 6 weeks. HDDS is best treated
      surgically. Early identification and stabilization of this challenging surgical
      entity could prevent the progression of slip and deformity making the index
      surgery less technically demanding. Vertebrae that are contained in the unstable
      zone can be instrumented and stabilized so that progression of the deformity and
      re-operation might be avoided. The authors suggested surgical technique can
      provide a way to restore sagittal balance, provide an environment for successful
      fusion, and decrease the risk of iatrogenic L5 neurologic injury.

PMID- 19399537
TI  - Individual, physical and psychological risk factors for neck pain in Australian
      office workers: a 1-year longitudinal study.
AB  - Neck pain is more prevalent in office workers than in the general community. To
      date, findings from prospective studies that investigated causal relationships
      between putative risk factors and the onset of neck pain in this population have
      been limited by high loss to follow-up. The aim of this research was to
      prospectively evaluate a range of risk factors for neck pain in office workers,
      using validated and reliable objective measures as well as attain an estimate of
      1-year incidence. We assembled a cohort of 53 office workers without neck pain
      and measured individual, physical, workplace and psychological factors at
      baseline. We followed participants for 1 year to measure the incidence of neck
      pain. We achieved 100% participant follow-up. Cox regression analysis was applied
      to examine the relationship between the putative risk factors and the cumulative
      incidence of neck pain. The 1-year incidence proportion of neck pain in
      Australian office workers was estimated in this study to be 0.49 (95% CI 0.36
      0.62). Predictors of neck pain with moderate to large effect sizes were female
      gender (HR: 3.07; 95% CI: 1.18-7.99) and high psychological stress (HR: 1.64; 95%
      CI: 0.66-4.07). Protective factors included increased mobility of the cervical
      spine (HR: 0.44; 95% CI: 0.19-1.05) and frequent exercise (HR: 0.64; 95% CI: 0.27
      1.51). These results reveal that neck pain is common in Australian office workers
      and that there are risk factors that are potentially modifiable.

PMID- 19399536
TI  - Two-level total lumbar disc replacement.
AB  - Total lumbar disc replacement (TDR) has been widely used as a treatment option
      for 2-level symptomatic degenerative disc disease. However, recent studies have
      presented conflicting results and some authors concluded that outcome
      deteriorated when disc replacement was performed bisegmentally, with an increase
      of complications for bisegmental replacements in comparison with monosegmental
      disc arthroplasty. The goal of the present retrospective study is to investigate
      results in a group of patients who have received bisegmental TDR with SB Charite
      III artificial disc for degenerative disc disease with a minimum follow-up of 3
      years, and to compare the results of 2-level disc replacement versus 1-level
      patients treated with the same prosthesis. A total of 32 patients had at least 3
      years follow-up and were reviewed. The average age of the patients was 38.5
      years. There were 11 males and 21 females. About 16 patients received 2-level TDR
      (SB Charite III) and 16 received 1-level TDR (SB Charite III). Both radiographic
      and functional outcome analysis, including patient's satisfaction, was performed.
      There were no signs of degenerative changes of the adjacent segments in any case
      of the 2- or 1-level TDR. There was no statistically significant difference
      between 2- and 1-level TDR both at 12 months and at 3-years follow-up on
      functional outcome scores. There was a statistically insignificant difference
      concerning the patients satisfaction between 1- and 2-level surgeries at the last
      follow-up (P = 0.46). In the 2-level TDR patients, there were 5 minor
      complications (31.25%), whereas major complications occurred in 4 more patients
      (25%) and required a new surgery in 2 cases (12.5%). In the 1-level cases there
      were 2 minor complications (12.5%) and 2 major complications (12.5%) and a new
      revision surgery was required in 1 patient (6.25%). In conclusion, the use of 2
      level disc replacement at last follow-up presented a higher incidence of
      complications than in cases with 1-level replacement. At the same time it was
      impossible to delineate a clear difference in evaluating the questionnaires
      between the follow-up results of patients receiving 2- and 1-level TDR: the 2
      level group presented slightly lower scores at follow-up, but none was
      statistically significant.

PMID- 19399538
TI  - Perioperative and short-term advantages of mini-open approach for lumbar spinal
      fusion.
AB  - It has been widely reported a vascular and neurologic damage of the lumbar
      muscles produced in the classic posterior approach for lumbar spinal fusions. The
      purpose of this study is to demonstrate a better clinical and functional outcome
      in the postoperative and short term in patients undergoing minimal invasive
      surgery ("mini-open") for this lumbar spinal arthrodesis. We designed a
      prospective study with a 30 individuals cohort randomized in two groups,
      depending on the approach performed to get a instrumented lumbar circumferential
      arthrodesis: "classic posterior" (CL group) or "mini-open" approach (MO group).
      Several clinical and functional parameters were assessed, including blood loss,
      postoperative pain, analgesic requirements and daily life activities during
      hospital stay and at the 3-month follow-up. Patients of the "mini-open approach"
      group had a significant lower blood loss and hospital stay during admission. They
      also had significant lower analgesic requirements and faster recovery of daily
      life activities (specially moderate efforts) when compared to the patients of the
      "classic posterior approach" group. No significant differences were found between
      two groups in surgery timing, X-rays exposure or sciatic postoperative pain. This
      study, inline with previous investigations, reinforces the concept of minimizing
      the muscular lumbar damage with a mini-open approach for a faster and better
      recovery of patients' disability in the short term. Further investigations are
      necessary to confirm these findings in the long term, and to verify the
      achievement of a stable lumbar spinal fusion.

PMID- 19399539
TI  - Three-dimensional localization of impacted teeth using magnetic resonance
      imaging.
AB  - Impacted teeth remain embedded in the jawbone beyond the normal eruption time
      with completed root growth. They can often get infected or damage neighboring
      teeth. Information about the three-dimensional position of impacted teeth is
      invaluable in orthodontic diagnosis and treatment planning. The purpose of this
      prospective study was to assess the feasibility of using magnetic resonance
      imaging (MRI) for the three-dimensional localization of impacted teeth in
      children and adults. The study included 39 patients from the pediatric age group
      with different tooth impactions and seven adults with impacted wisdom teeth. MRI
      yielded a clear separation between impacted teeth and the surrounding tissue, and
      the position and angulation of impacted teeth in all three spatial dimensions
      could be assessed. Compared to conventional radiography, dental MRI provides the
      advantage of full volumetric morphology accompanied by complete elimination of
      ionizing radiation, which is particularly relevant for repeated examinations of
      the pediatric group.

PMID- 19399540
TI  - The anti-inflammatory non-antibiotic helper compound diclofenac: an antibacterial
      drug target.
AB  - Diclofenac sodium (Dc) was found to possess antibacterial activity against both
      drug-sensitive and drug-resistant clinical isolates of Staphylococcus aureus,
      Listeria monocytogenes, Escherichia coli, and Mycobacterium spp., in addition to
      its potent anti-inflammatory activity. The time-kill curve study indicates that
      this non-steroidal drug exhibits bactericidal activity against Listeria, E. coli,
      and M. tuberculosis. The antibacterial activity of Dc comes, in part, from its
      ability to inhibit the DNA synthesis of E. coli and L. monocytogenes. Dc could
      protect murine listeriosis, salmonellosis, and tuberculosis at doses ranged
      within its maximum recommended human or non-toxic ex-vivo dose. Dc possesses anti
      plasmid activity and acts as a 'helper compound' in synergistic combination with
      streptomycin against E. coli and Mycobacterium or gentamicin against Listeria.
      This review focuses on the possible use of Dc, a non-antibiotic helper compound,
      in infections and inflammatory conditions, rationalized on the basis of the
      activities of the compounds.

PMID- 19399541
TI  - Comprehensive reviews of the interfascial plane of the retroperitoneum: normal
      anatomy and pathologic entities.
AB  - The retroperitoneum is conventionally divided into three distinct compartments:
      posterior pararenal space, anterior pararenal space, and perirenal space, bounded
      by the posterior parietal peritoneum, transversalis fascia, and perirenal fascia.
      But more recent work has demonstrated that the perirenal fascia is not made up of
      distinct unilaminated fascia, but a single multilaminated structure with
      potential space. These potential spaces are represented by retromesenteric plane,
      retrorenal plane, lateral conal plane, and combined fascial plane. The purpose of
      this review was to demonstrate embryogenesis, anatomy of interfascial plane, and
      spreading pathways of various pathologic entities with computed tomography
      imaging.

PMID- 19399542
TI  - Self-organizing map-based multi-thresholding on neural stem cells images.
AB  - Automatic segmentation and tracking systems can be useful tools for biologists to
      monitor and understand the proliferation and the differentiation of neural stem
      cells. This paper applied the self-organizing map-based multi-thresholding on the
      neural stem cells images. Using local variance as the local spatial feature and
      quadtree decomposition as the sub-sampling method, inner-cell regions, cell
      borders and background can be roughly classified. Based on these results, proper
      foreground and background seeds were constructed for the seeded watershed
      segmentation and every single cell in a cell cluster can be segmented correctly.
      The results were also compared to the seeded watershed segmentation based on
      regional maxima method.

PMID- 19399543
TI  - The effect of elbow joint centre displacement on force generation and neural
      excitation.
AB  - Joint centre displacement may occur following total elbow replacement due to
      aseptic loosening or surgical misalignment, and has been linked to implant
      failure. In this study, the effects of joint centre displacement were examined
      using a neuromusculoskeletal model of the elbow joint. Isometric contractions
      were simulated at a range of joint angles during elbow flexion and extension.
      Displacement of the joint centre affected the force-generating capacity about the
      joint, due to changes in both muscle lengths and moment arms. The magnitude and
      direction of the maximum joint reaction force were also altered, potentially
      contributing to aseptic loosening and compromising joint stability. The
      relationship between force generated and the level of neural excitation to the
      elbow flexor and extensor muscles was also affected, suggesting that altered
      neural control patterns could be required following joint centre displacement.

PMID- 19399544
TI  - Symbiogenesis, natural selection, and the dynamic Earth.
AB  - One century ago, Constantin S. Mereschkowsky introduced the symbiogenesis theory
      for the origin of chloroplasts from ancient cyanobacteria which was later
      supplemented by Ivan E. Wallin's proposal that mitochondria evolved from once
      free-living bacteria. Today, this Mereschkowsky-Wallin principle of
      symbiogenesis, which is also known as the serial primary endosymbiosis theory,
      explains the evolutionary origin of eukaryotic cells and hence the emergence of
      all eukaryotes (protists, fungi, animals and plants). In 1858, the concept of
      natural selection was described independently by Charles Darwin and Alfred R.
      Wallace. In the same year, Antonio Snider-Pellegrini proposed the idea of
      shifting continents, which was later expanded by Alfred Wegener, who published
      his theory of continental drift eight decades ago. Today, directional selection
      is accepted as the major cause of adaptive evolution within natural populations
      of micro- and macro-organisms and the theory of the dynamic Earth (plate
      tectonics) is well supported. In this article, I combine the processes and
      principles of symbiogenesis, natural selection and the dynamic Earth and propose
      an integrative 'synade-model' of macroevolution which takes into account
      organisms from all five Kingdoms of life.

PMID- 19399545
TI  - Short-term outcome of anorexia nervosa in adolescents after inpatient treatment:
      a prospective study.
AB  - The current study describes the short-term outcome of adolescent inpatient
      population suffering from anorexia nervosa (AN) and analyzes the clinical
      predictors of poor outcome in these patients. Fifty-seven female AN patients
      (mean = 15.8, SD = 1.3) admitted for inpatient treatment to a specialized eating
      disorder unit at a university medical center were reassessed 1 year after being
      discharged. Assessments were made at the beginning and at the end of the
      inpatient treatment as well as at the 1-year follow-up. Self-rating data and
      expert-rating interview data were obtained. Adequate data for 55 (96.5%) cases
      allowed for the assignment of an outcome category. A total of 28.1% of the
      patients' cases showed a good outcome, meaning the patients fully recovered, and
      8.8% had an intermediate outcome, and 59.6% of the patients' cases had a poor
      outcome. Significant predictors of poor outcome included the patient's BMI at the
      beginning of the treatment as well as psychiatric comorbidity, and purging
      behavior. Adolescent AN is a severe disorder with a poor outcome in a substantial
      amount of adolescents.

PMID- 19399546
TI  - Impact of life events on child mental health before school entry at age six.
AB  - The study examined the association between life events and early child mental
      health prior to school entry. The impact of single life events and the cumulative
      effect of multiple life events on child mental health were examined. In a
      northern German city, the complete 1-year intake of preschool children at the
      primary school entry assessment was included. In 1,887 children, life events and
      psychiatric symptoms were recorded by means of standardized parent
      questionnaires. Included were all life events between child's birth and school
      entry. For more than 80 percent of all children, at least one life event was
      reported. The number of life events was independent of any demographic variable;
      the mean was 2.2. The number of life events had a highly significant effect on
      the prevalence of child mental health problems. Six family-change-factors,
      especially coherent in content, could be identified by factor analysis. The study
      provides important data on the epidemiology and clinical impact of life events
      and psychopathology in early childhood. For child mental health, the cumulative
      effect of multiple life events was found to be much more important than the
      effect of specific single life events.

PMID- 19399547
TI  - Autoimmune autonomic ganglionopathy: treatment by plasma exchanges and rituximab.
AB  - This case report describes successful treatment of autoimmune autonomic
      ganglionopathy (AAG) in a 74-year-old woman by total plasma exchanges (PLEX) and
      rituximab. Two series of PLEX temporarily, but dramatically improved orthostatic
      intolerance and hypotension and baroreflex function, in a manner inversely
      related to ganglionic neuronal nicotinic receptor antibody titer. After rituximab
      treatment, the antibody titer was decreased modestly but persistently, and the
      patient had symptomatic and clinical laboratory evidence of continued benefit for
      at least 10 months, supporting the autoimmune pathogenesis of AAG.

PMID- 19399548
TI  - Agricultural pesticides in Mississippi Delta oxbow lake sediments during autumn
      and their effects on Hyalella azteca.
AB  - Agricultural pesticide contamination of sediments from five Mississippi Delta
      oxbow lakes and their effects and bioavailablity to Hyalella azteca were assessed
      during a low-application season-autumn. Three reference oxbow lakes were located
      in the White River National Wildlife Refuge (WRNWR), Arkansas and two impaired
      lakes, according to the US Environmental Agency Sect. 303 (d) Clean Water Act,
      were located in Mississippi. Surface sediment (top 5 cm) was collected at three
      sites within each lake and analyzed for 17 current and historic-use pesticides
      and metabolites. Chronic 28-day H. azteca sediment bioassays and pesticide body
      residue analyses were completed to determine the degree of biological responses
      and bioavailability. The greatest number of detectable pesticides in WRNWR and
      303 (d) sediment samples was 9 and 12, respectively, with historic-use pesticide
      metabolite, p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] ubiquitous.
      No significant (p > 0.05) differences in animal survival were observed among
      sites. Animal growth was significantly (p < 0.05) less at only one site in a 303
      (d)-listed lake (Macon Lake). Only six pesticides were observed in H. azteca with
      current-use pesticides detected at three sites; historic-use pesticides and
      metabolites detected at 11 sites. Animal body residues of a historic-use
      pesticide (dieldrin) and metabolite (p,p'-DDE) were associated with observed
      growth responses. Results show limited current-use pesticide contamination of
      sediments and H. azteca body tissues during autumn and that historic-use
      pesticides and metabolites are the primary contributors to observed biological
      responses.

PMID- 19399549
TI  - Acrosome reaction of sperm in the mud crab Scylla serrata as a sensitive toxicity
      test for metal exposures.
AB  - In order to test the sensitivity of the sperm cell of the mud crab Scylla serrata
      to heavy metals, the toxic effects of Ag+, Cd2+, Cu2+, and Zn2+ on the acrosome
      reaction (AR) were studied by artificially inducing the AR of sperm exposed to
      heavy metals, counting the AR rates by light microscopy, and observing structural
      changes in sperm by transmission electron microscopy. The AR in S. serrata occurs
      at two stages. The first stage (ARI) is the eversion of the subacrosomal
      material. The second stage (ARII) is the ejection of the acrosomal filament. The
      results showed the EC50 values of the AR based on (ARI + ARII)% for Ag+, Cd2+,
      Cu2+, and Zn2+ were 10.02, 2.14, 13.69, and 2.21 microg/L, and the EC50 values
      based on ARII % of Ag+, Cd2+, Cu2+, and Zn2+ were 1.96, 0.20, 1.46, and 0.34
      microg/L. The order of toxicity is Cd2+ > Zn2+ > Cu2+ > Ag+ based on the
      percentage of reacted sperm at the second stage. Sperm cells exposed to heavy
      metals showed an increased rate of swelling, shape irregularities, and the
      acrosomal filament of some sperm cells was, crooked, ruptured, and even
      dissolved. The AR of the sperm cell from S. serrata is more sensitive to the
      tested heavy metals compared to sea urchin sperm cell toxicity tests.

PMID- 19399550
TI  - Effects of early oral feeding on surgical outcomes and recovery after curative
      surgery for gastric cancer: pilot study results.
AB  - BACKGROUND: The aim of the present study was to determine whether early oral
      feeding after curative resection for gastric cancer can be tolerated and whether
      it has an effect on recovery. METHODS: From September 2007 to January 2008, we
      provided early postoperative oral feeding for 35 patients who underwent curative
      distal gastrectomy for gastric cancer. These patients began a liquid diet on the
      second postoperative day (POD), followed by a soft diet beginning on the third
      POD until they were discharged. From April to August 2007, we enrolled 31
      patients with a conventional diet schedule as a control group. We compared the
      clinicopathologic features and surgical outcomes, including morbidity, laboratory
      results, and hospitalized days between the two groups. RESULTS: There were no
      significant differences in the clinical and operative factors between the two
      groups. Although there was no difference in the morbidity rate (P = 0.331), the
      early group was hospitalized for fewer days (8.03 +/- 1.43 vs. 9.97 +/- 2.07
      days; P < 0.001) and had a faster onset of flatus (1.96 +/- 0.58 vs. 2.97 +/-
      0.66 day; P < 0.001) than the control group. The laboratory findings showed that
      the early feeding group tended to have a lymphocyte count that recovered faster
      than the control group, although the difference was not statistically
      significant. CONCLUSIONS: Early oral feeding following a gastrectomy for gastric
      cancer is feasible and can result in faster recovery of bowel function and a
      shorter hospitalization.

PMID- 19399551
TI  - Evidence of maternal QTL affecting growth and obesity in adult mice.
AB  - Most quantitative trait loci (QTL) studies fail to account for the effect that
      the maternal genotype may have on an individual's phenotypes, even though
      maternal effect QTL have been shown to account for considerable variation in
      growth and obesity traits in mouse models. Moreover, the fetal programming theory
      suggests that maternal effects influence an offspring's adult fitness, although
      the genetic nature of fetal programming remains unclear. Within this context, our
      study focused on mapping genomic regions associated with maternal effect QTL by
      analyzing the phenotypes of chromosomes 2 and 7 subcongenic mice from genetically
      distinct dams. We analyzed 12 chromosome 2 subcongenic strains that spanned from
      70 to 180 Mb with CAST/EiJ donor regions on the background of C57BL/6 J, and 14
      chromosome 7 subcongenic strains that spanned from 81 to 111 Mb with BALB/cByJ
      donor regions on C57BL/6ByJ background. Maternal QTL analyses were performed on
      the basis of overlapping donor regions between subcongenic strains. We identified
      several highly significant (P < 5 x 10(-4)) maternal QTL influencing total body
      weight, organ weight, and fat pad weights in both sets of subcongenics. These QTL
      accounted for 1.9-11.7% of the phenotypic variance for growth and obesity and
      greatly narrowed the genomic regions associated with the maternal genetic
      effects. These maternal effect QTL controlled phenotypic traits in adult mice,
      suggesting that maternal influences at early stages of development may
      permanently affect offspring performance. Identification of maternal effects in
      our survey of two sets of subcongenic strains, representing approximately 5% of
      the mouse genome, supports the hypothesis that maternal effects represent
      significant sources of genetic variation that are largely ignored in genetic
      studies.

PMID- 19399552
TI  - Normal spirometric reference values for Omani adults.
AB  - International guidelines recommend the use of population-specific reference
      values to eliminate the well-recognized influence of ethnic variation on lung
      function. This study was designed to derive spirometric prediction equations for
      healthy Omani adults. Forced vital capacity (FVC), forced expiratory volume in
      one second (FEV(1)), peak expiratory flow rate (PEFR), and forced expiratory flow
      at 25% to 75% of FVC (FEF(25-75%)) were measured in 419 "healthy" nonsmoking
      Omani adults (256 men, 163 women), aged 18-65 years. Multiple linear regression
      analysis was performed for each spirometric parameter against age, height, and
      weight for men and women separately, and prediction equations for all the above
      parameters were derived and compared with values derived using equations
      published from other populations. All measured spirometric parameters increased
      with height and decreased with age, and they were all significantly higher in
      men. In contrast, FEV(1)/FVC% values decreased with height and increased with age
      and were higher in women. The predicted normal values of FVC and FEV(1) for our
      subjects using the derived equations were lower by 7-17% compared with respective
      Caucasian values, with smaller difference in the predicted values of PEFR,
      FEV(1)/FVC%, and FEF(25-75%). This report presents previously unavailable
      spirometric reference equations for the Omani adults. Our findings highlight the
      need to use reference values based on updated data derived from relevant
      populations.

PMID- 19399553
TI  - Impaired sleep reduces quality of life in chronic obstructive pulmonary disease.
AB  - Disturbed sleep is reportedly common in chronic obstructive pulmonary disease
      (COPD), but the impact of quality of sleep on health-related quality of life
      (HRQL) has not been previously investigated in these individuals. The purpose of
      this study was to assess the impact of quality of sleep on HRQL in patients with
      COPD. In 30 clinically stable patients with moderate to very severe COPD, we
      evaluated subjective sleep quality using the Pittsburgh Sleep Quality Index
      (PSQI) and HRQL using the Saint George's Respiratory Questionnaire. Additionally,
      lung function was assessed by spirometry, severity of dyspnea by the Modified
      Medical Research Council scale, and functional exercise capacity by the Six
      Minute Walk Test. Twenty-one (70%) patients showed poor quality of sleep (PSQI >
      5). HRQL was significantly correlated with quality of sleep (P = 0.02), post
      bronchodilator FEV1 (P = 0.04), and severity of dyspnea (P < 0.01). Multiple
      regression analysis showed that quality of sleep was the best predictor of
      quality of life in our subjects. Our data suggest that quality of sleep is major
      determinant of HRQL in COPD. Increased efforts to diagnose and treat sleep
      problems, including measures to improve factors that adversely affect sleep
      should receive great attention in the daily management of these patients.

PMID- 19399554
TI  - Validation of ICD-9 Code 787.2 for identification of individuals with dysphagia
      from administrative databases.
AB  - The aim of this study was to determine the accuracy of dysphagia coding using the
      International Classification of Diseases version 9 (ICD-9) code 787.2. We used
      the administrative database of a tertiary hospital and sequential
      videofluorographic swallowing study (VFSS) reports for patients admitted to the
      same hospital from January to June 2007. The VFSS reports were abstracted and the
      hospital's database was queried to abstract the coding associated with the
      admission during which the VFSS was performed. The VFSS and administrative data
      were merged for data analysis. Dysphagia was coded (using code 787.2) in 36 of
      168 cases that had a VFSS. Of these, 34 had dysphagia diagnosed by VFSS (our gold
      standard) and one had a prior history of dysphagia. Code 787.2 had sensitivity of
      22.8, specificity of 89.5, and positive and negative predictive values of 94.4
      and 12.9, respectively. Dysphagia was largely undercoded in this database, but
      when the code was present those individuals were very likely to be dysphagic.
      Selection of dysphagic cases using the ICD-9 code is appropriate for within-group
      comparisons. Absence of the code, however, is not a good predictor of the absence
      of dysphagia.

PMID- 19399555
TI  - Brain stem control of the phases of swallowing.
AB  - The phases of swallowing are controlled by central pattern-generating circuitry
      of the brain stem and peripheral reflexes. The oral, pharyngeal, and esophageal
      phases of swallowing are independent of each other. Although central pattern
      generators of the brain stem control the timing of these phases, the peripheral
      manifestation of these phases depends on sensory feedback through reflexes of the
      pharynx and esophagus. The dependence of the esophageal phase of swallowing on
      peripheral feedback explains its absence during failed swallows. Reflexes that
      initiate the pharyngeal phase of swallowing also inhibit the esophageal phase
      which ensures the appropriate timing of its occurrence to provide efficient bolus
      transport and which prevents the occurrence of multiple esophageal peristaltic
      events. These inhibitory reflexes are probably partly responsible for deglutitive
      inhibition. Three separate sets of brain stem nuclei mediate the oral,
      pharyngeal, and esophageal phases of swallowing. The trigeminal nucleus and
      reticular formation probably contain the oral phase pattern-generating neural
      circuitry. The nucleus tractus solitarius (NTS) probably contains the second
      order sensory neurons as well as the pattern-generating circuitry of both the
      pharyngeal and esophageal phases of swallowing, whereas the nucleus ambiguus and
      dorsal motor nucleus contain the motor neurons of the pharyngeal and esophageal
      phases of swallowing. The ventromedial nucleus of the NTS may govern the coupling
      of the pharyngeal phase to the esophageal phase of swallowing.

PMID- 19399556
TI  - Gustatory responsiveness to six bitter tastants in three species of nonhuman
      primates.
AB  - Gustatory responsiveness of six adult squirrel monkeys, four spider monkeys, and
      five pigtail macaques to six bitter tastants was assessed in two-bottle
      preference tests of brief duration (2 min). Animals were given the choice between
      a 30-mM sucrose solution and defined concentrations of a bitter tastant dissolved
      in a 30-mM sucrose solution. With this procedure, Saimiri sciureus, Ateles
      geoffroyi, and Macaca nemestrina were found to significantly discriminate
      concentrations as low as 0.2, 0.05, and 0.1 mM quinine hydrochloride; 1, 1, and
      0.05 mM caffeine; 20, 5, and 1 mM naringin; 5, 2, and 1 mM salicin; 0.01, 0.001,
      and 0.02 mM sucrose octaacetate; and 0.05, 0.01, and 0.5 mM denatonium benzoate,
      from the alternative stimulus. With the exception of naringin in the pigtail
      macaques, all three species rejected all suprathreshold concentrations of all
      bitter tastants tested. The spider monkeys and the pigtail macaques displayed the
      lowest taste avoidance thresholds with three of the six tastants each; in
      contrast, the squirrel monkeys displayed the highest taste avoidance thresholds
      with four of the six tastants. The across-tastant patterns of taste avoidance
      thresholds were identical in spider monkeys and squirrel monkeys; both species
      displayed the following order of sensitivity: sucrose octaacetate > denatonium
      benzoate > quinine hydrochloride > caffeine > salicin > naringin. All three
      primate species were more sensitive to the two artificial tastants (sucrose
      octaacetate and denatonium benzoate) compared to the four naturally occurring
      tastants. However, the concentrations detected by all three primate species with
      the four naturally occurring tastants are well below those reported in plants or
      arthropods consumed by these species suggesting that they may use bitterness as a
      criterion for food selection.

PMID- 19399557
TI  - Cuticular hydrocarbon phenotypes do not indicate cryptic species in fungus
      growing termites (Isoptera: Macrotermitinae).
AB  - In several termite species, distinct differences in the composition of cuticular
      hydrocarbons among colonies correspond to high genetic divergence of
      mitochondrial DNA sequences. These observations suggest that hydrocarbon
      phenotypes represent cryptic species. Different cuticular hydrocarbon phenotypes
      also are found among colonies of fungus-growing termites of the genus
      Macrotermes. To determine if these hydrocarbon differences in Macrotermes also
      indicate cryptic species, we sequenced the mitochondrial CO I gene from species
      in West and East Africa. Among individuals of a supposed species but belonging to
      different cuticular hydrocarbon phenotypes, the genetic distances are much
      smaller than distances between species. Unlike what has been observed in other
      termites, Macrotermes hydrocarbon phenotypes do not represent cryptic species.
      Our findings suggest fundamental differences in the evolution and/or function of
      cuticular hydrocarbons among different termite lineages.

PMID- 19399558
TI  - Consensus science and the peer review.

PMID- 19399559
TI  - Type IV FDP avulsion: lessons learned clinically and through review of the
      literature.
AB  - The type IV flexor digitorum profundus avulsion is a rare injury involving
      fracture of the volar base of the distal phalanx and separation of the tendon
      from the fracture fragment. Recommendations for management are sparse and are
      substantiated only by a few isolated case reports. We recently encountered two of
      these injuries, both of which proved challenging, particularly with regard to
      joint incongruity and tendon adhesions. In reviewing the literature, it is
      apparent that no consensus exists regarding surgical strategies. However, based
      on our experience and that of other authors, we can suggest the following: (1)
      high index of suspicion of this potentially deceptive injury, with use of
      magnetic resonance imaging or ultrasound if preoperative confirmation is needed;
      (2) rigid bony fixation that prevents dorsal subluxation of the distal phalanx;
      (3) tendon repair that is independent of the bony fixation; and (4) early range
      of motion therapy.

PMID- 19399560
TI  - Reconstructing the rheumatoid wrist: a utility analysis comparing total wrist
      fusion and total wrist arthroplasty from the perspectives of rheumatologists and
      hand surgeons.
AB  - Rheumatologists and hand surgeons have historically demonstrated strikingly
      divergent attitudes toward the benefits of surgical intervention, either total
      wrist fusion or total wrist arthroplasty, for the rheumatoid wrist. A utility
      analysis was conducted to compare a national random sample of hand surgeons and
      rheumatologists regarding their opinions about surgical management of severe
      rheumatoid wrist disease. A web-based trade-off utility survey was developed, and
      participants were presented with survey scenarios comparing well-controlled
      rheumatoid arthritis with operative and non-operative management. Utility values
      were calculated for each scenario, and a decision analytic model was constructed.
      Utility values for rheumatologists and hand surgeons did not differ significantly
      for any scenario. Total wrist arthroplasty was associated with the highest
      expected gain in quality-adjusted life-years for each subgroup. This decision
      analytic model demonstrates similar opinions between two subspecialties that have
      historically demonstrated divergent attitudes towards rheumatoid hand surgery.

PMID- 19399561
TI  - Risk factors for morbidity and mortality following gastroenterostomy.
AB  - BACKGROUND: Morbidity and mortality following traditional surgical treatment of
      gastric outlet obstruction is high. The aim of this work was to identify risk
      factors predictive of postoperative complications and mortality following
      gastroenterostomy. METHODS: One-hundred sixty-five consecutive patients subjected
      to open gastroenterostomy from January 1996 through July 2003 were included. Data
      on vital signs and operative variables were retrieved from medical records and
      recorded retrospectively. Risk factors for postoperative complications and
      mortality within 30 days after operation were analyzed with multiple logistic
      regression. RESULTS: The 30-day complication and death rates were higher after
      emergency operations (80% and 60%) than after elective operations (32% and 25%).
      A multivariate analysis disclosed that hypoalbuminemia (< or = 32 g/l),
      comorbidity, high age, and hyponatremia (< 135 micromol/l) were significantly
      associated with postoperative death, whereas hypoalbuminemia, comorbidity, high
      age, and emergency operation were predictors of postoperative complications.
      CONCLUSIONS: Complications and mortality after gastroenterostomy due to gastric
      outlet obstruction are associated with modifiable and non-modifiable risk
      factors. Prior to surgery means should be taken to correct low albumin and sodium
      levels to prevent complications. In addition, the surgeon should consider
      alternative treatment modalities including laparoscopic gastroenterostomy, self
      expanding metallic stents, or tube gastrostomy to relieve or palliate gastric
      outlet obstruction.

PMID- 19399562
TI  - Stents, glue, etc.: is anything proven to help prevent pancreatic leaks/fistulae?

PMID- 19399563
TI  - Energy expenditure and weight regain in patients submitted to Roux-en-Y gastric
      bypass.
AB  - BACKGROUND: Although Roux-en-Y gastric bypass (RYGBP) is a highly effective
      treatment for clinically severe obesity, not all patients achieve desirable
      weight loss and maintenance. There is some evidence that weight loss can induce a
      disproportionate reduction in resting metabolic rate (RMR). This reduction in RMR
      can be related to fat-free mass (FFM) loss, as FFM is the greatest responsible
      for variations in energy expenditure at rest. Abnormally low basal metabolic rate
      may predispose surgical patients to weight regain. METHOD: Thirty-six individuals
      were divided into two groups: patients who have kept a healthy weight 2 years
      after surgery and patients who showed weight regain of at least 2 kg 2 years
      after the surgery. Selected patients have signed a consent form. Body mass index
      and excess weight loss were evaluated. RMR and body fat percentage were measured.
      FFM is a heterogeneous component that can be partitioned into muscle mass and no
      muscle mass. The FFM was calculated as the result of subtracting total fat weight
      from total body weight in kilogram. We also wanted to know if the predictive
      formulas to assess RMR overestimate energy expenditure in these patients.
      Statistical tests were used to analyze the two groups. RESULTS: We found out that
      the RMR of the weight regain group was statistically inferior to the mean of the
      healthy weight group-the difference between the two groups was about 260
      kcal/day. We also found out that the predictive formulas overestimate the RMR in
      the weight regain group. CONCLUSION: This study suggests that a lower RMR may
      contribute to weight regain in patients who undergo RYGBP. It is important to
      ensure ways to elevate energy expenditure in the patient, such as increasing the
      percentage of fat-free mass in the body and the practice of physical activities.

PMID- 19399564
TI  - An 11-year-old boy with a patella fracture.

PMID- 19399565
TI  - 2009 Nicolas Andry Award: clinical biomechanics of third body acceleration of
      total hip wear.
AB  - Aseptic loosening attributable to wear-related osteolysis historically has been
      the predominant cause of failure in THA. Advances in low-wear bearing couples
      show great promise to substantially reduce this long-standing problem. However,
      there always has been striking variability in wear rate in any given cohort of
      patients who are similarly implanted, with some individuals typically
      experiencing near order-of-magnitude elevations above group mean. Third-body wear
      is likely a major contributor to many of these most osteolysis-prone outliers.
      For the patients affected, third-body effects may obviate many of the gains
      otherwise achieved by contemporary bearing surface improvements. Toward
      heightening visibility in terms of consequences for patients, this review paper
      summarizes an interrelated series of investigations quantifying construct level
      manifestations of third-body wear. Long-term followup of a unique group of
      patients with elevated third-body challenge shows statistically significant and
      clinically important wear-rate increases. A series of finite element models,
      validated physically, shows the linkage of location of third-body damage with
      variability of volumetric wear-rate acceleration and shows the effects of various
      implant factors, surgeon factors, and patient factors in the presence of third
      body challenge. Finally, a mechanism for third-body debris access to wear
      critical locations on the bearing surface is identified analytically and
      corroborated in laboratory experiments and implant retrievals.

PMID- 19399566
TI  - Coronary CT angiography (CCTA) and advances in CT plaque imaging.
AB  - The goal of this review is to highlight current advances in the non-invasive
      detection of clinically significant atherosclerotic disease including the so
      called vulnerable plaque with computed tomography. Atherosclerotic disease
      encompasses stages of plaque progression, stabilization, and even regression.
      Traditionally, the focus of diagnostic imaging has been the detection of lumen
      occluding atheroma. However, advances in our understanding of the pathophysiology
      of atherosclerotic plaque have shown that, in certain stages of plaque
      progression, plaque is "vulnerable" and able to cause acute coronary syndromes
      despite "non-significant" vascular occlusion at baseline. This provides a
      rationale to improve our non-invasive imaging technology. Presented here are
      improvements in soft-tissue resolution with technical advancements as well as
      contrast-enhancement and lately even nanotechnology-based technology which are
      geared to detect the clinically elusive vulnerable plaque and provide an
      opportunity for preventative therapy.

PMID- 19399567
TI  - Chronic kidney disease, SPECT, and coronary angiography: "head of gold and feet
      of clay?".

PMID- 19399568
TI  - New software methods to cope with reduced counting statistics: shorter SPECT
      acquisitions and many more possibilities.

PMID- 19399569
TI  - Molecular imaging of ventricular remodeling.

PMID- 19399570
TI  - Ultrasound guidance to facilitate low interscalene brachial plexus block in a
      patient with indwelling hemodialysis catheter.

PMID- 19399571
TI  - Preparation of the Drager Fabius GS workstation for malignant hyperthermia
      susceptible patients.
AB  - PURPOSE: In order to establish guidelines for the preparation of the Drager
      Fabius GS premium anesthetic workstation for malignant hyperthermia-susceptible
      patients, the authors evaluated the effect of the workstation's exchangeable and
      autoclavable components on the washout of isoflurane. METHODS: A Drager Fabius GS
      workstation was primed with 1.5% isoflurane, and exchangeable components were
      replaced as follows: Group 1: no replacement (control); Group 2: autoclaved
      ventilator diaphragm and ventilator hose; Group 3: flushed ventilator diaphragm
      and ventilator hose; Group 4: autoclaved compact breathing system. The fresh gas
      flow (FGF) was set at 10 L . min(-1), and the concentration of isoflurane in the
      inspiratory limb of the circle breathing circuit was recorded every minute until
      an endpoint of 5.0 parts per million (ppm) was achieved, at which time the FGF
      was reduced to 3 L . min(-1). Six experiments were conducted in each of the four
      groups. RESULTS: The time to achieve an isoflurane concentration of 5.0 ppm
      decreased in the following order: Group 1 (151 +/- 17 min) > Group 3 (137 +/- 7
      min) > Group 4 (122 +/- 11 min) > Group 2 (42 +/- 6 min) (P < 0.01 vs control).
      Isoflurane concentration increased approximately fivefold when the FGF was
      reduced to 3 L . min(-1). CONCLUSION: Anesthetic washout from the Drager Fabius
      GS is relatively slow. Although washout was accelerated when the Drager Fabius GS
      was equipped with autoclaved components, the reduction in washout time may be
      less than that required for this technique to be accepted into clinical practice.
      A dedicated vapor-free workstation may be preferable for rapid turnover between
      cases.

PMID- 19399572
TI  - Nasogastric tube insertion assisted with the AirwayScope in a patient with
      cervical spine instability.

PMID- 19399573
TI  - Stress-induced cardiomyopathy in the perioperative setting.

PMID- 19399574
TI  - Optimizing preoxygenation in adults.
AB  - PURPOSE: Preoxygenation increases oxygen reserves and duration of apnea without
      desaturation (DAWD), thus it provides valuable additional time to secure the
      airway. The purpose of this Continuing Professional Development (CPD) module is
      to examine the various preoxygenation techniques that have been proposed and to
      assess their effectiveness in healthy adults and in obese, pregnant, and elderly
      patients. PRINCIPAL FINDINGS: The effectiveness of preoxygenation techniques can
      be evaluated by measuring DAWD, i.e., the time for oxygen saturation to decrease
      to <90%. Clinically, preoxygenation is considered adequate when end-tidal oxygen
      fraction is >90%. This is usually achieved with a 3-min tidal volume breathing
      (TVB) technique. As a rule, asking the patient to take four deep breaths in 30
      sec (4 DB 30 sec) yields poorer results. Eight deep breaths in 60 sec (8 DB 60
      sec) is equivalent to TVB 3 min. The DAWD is decreased in obese patients,
      pregnant women, and patients with increased metabolism. Obese patients may
      benefit from the head-up position and positive pressure breathing. A TVB
      technique is preferable in the elderly. Failure to preoxygenate is often due to
      leaks, which commonly occur in edentulous or bearded patients. In cases of
      difficult preoxygenation, directly applying the circuit to the mouth might be a
      useful alternative. Supplying extra oxygen in the nasopharynx during apnea might
      increase DAWD. CONCLUSION: Since ventilation and tracheal intubation difficulties
      are unpredictable, this CPD module recommends that all patients be preoxygenated.
      The TVB 3 min and the 8 DB 60 sec techniques are suitable for most patients;
      however, the 4 DB 30 sec is inadequate.

PMID- 19399575
TI  - Pericardial tamponade.

PMID- 19399576
TI  - Comparative phylogeography of two closely related Viola species occurring in
      contrasting habitats in the Japanese archipelago.
AB  - Similar distribution ranges shared by closely related plant species may have been
      shaped through different migration histories if those species have differing
      habitat preference. To test this hypothesis, phylogeographical patterns and
      population genetic structures were compared between two sister Viola species:
      Viola eizanensis preferring woodland and V. chaerophylloides var. sieboldiana
      preferring grassland, both being native to the Japanese Archipelago. Amplified
      fragment length polymorphism (AFLP) was used for phylogenetic reconstruction,
      together with Bayesian ancestry analysis, AMOVA, analysis of genetic diversity
      statistics, and analysis of the relative contribution of each population to total
      diversity. The results indicated that V. eizanensis had two distinct lineages
      occurring in the western and eastern part of Japan, but such lineages are not
      distinct in V. chaerophylloides var. sieboldiana. Both species exhibited the low
      genetic diversity and high between-population differentiation typical of selfing
      plants. In V. chaerophylloides var. sieboldiana, one particular population made a
      significantly higher contribution to the total heterozygosity (H (T)), whereas in
      V. eizanensis, no population was identified as making a particularly higher
      contribution to H (T). These findings suggest that V. eizanensis had been
      isolated in two large glacial refugia, whereas populations of V. chaerophylloides
      var. sieboldiana were restricted to a single small refuge. Different light
      requirements between these two closely related species probably caused these
      differing responses to climatic change during the last ice age.

PMID- 19399577
TI  - Extract from Calotropis procera latex activates murine macrophages.
AB  - Calotropis procera latex has long been used in traditional medicines. Extracts
      from C. procera latex have been reported to have various pharmacological actions,
      including protection from myocardial infarction, hepatoprotective action,
      antitumor activity, antinociceptive, and pro- and anti-inflammatory actions. To
      evaluate the immunomodulatory functions of the water-soluble C. procera extract
      (CPE), we investigated its ability to activate macrophages-effector cells in
      inflammatory and immune responses. Intraperitoneal injection of CPE in mice (2
      mg/mouse) induced migration of macrophages to the intraperitoneal cavity,
      confirming the proinflammatory effects of water-soluble CPE. The direct effects
      of CPE on macrophages were then assessed by measuring the production of nitric
      oxide (NO) as an indicator for macrophage activation. Addition of CPE (1-10
      microg/ml) to the culture medium of the murine monocyte/macrophage cell line
      RAW264.7 caused an increase in NO production in a time- and dose-dependent
      manner. CPE-elicited NO production was blocked by application of an inhibitor of
      inducible nitric oxide synthase (iNOS). Expression of iNOS mRNA was induced by
      treatment of cultured macrophages with CPE. Injection of CPE in mice also
      resulted in an increase in plasma NO level. The results suggest that CPE
      activates macrophages and facilitates NO production via up-regulation of iNOS
      gene expression.

PMID- 19399578
TI  - Kopsiyunnanines F and isocondylocarpines: new tubotaiwine-type alkaloids from
      Yunnan Kopsia arborea.
AB  - Five new alkaloids, including three 19,20-epoxytubotaiwine stereoisomers, viz.
      kopsiyunnanines F1 (1), F2 (2), and F3 (3), (Z)-isocondylocarpine (4), and (Z)
      isocondylocarpine N-oxide (5), along with five known tubotaiwine-type indole
      alkaloids were isolated from the aerial part of Yunnan Kopsia arborea Blume
      (Apocynaceae). Their structures including absolute configurations were elucidated
      by spectroscopic and chemical means.

PMID- 19399579
TI  - Significance of (18)F-2-deoxy-2-fluoro-glucose accumulation in the stomach on
      positron emission tomography.
AB  - OBJECTIVE: To explain the accumulation of (18)F-2-deoxy-2-fluoro-glucose
      ((18)FDG) on positron emission tomography (PET) in the stomach and differences in
      its pattern, we focus on the accumulation pattern in association with endoscopic
      findings of the gastric mucosa and Helicobacter pylori (Hp) infection. METHODS:
      Of 599 cases undergoing (18)FDG-PET examinations, we retrospectively analyzed the
      pattern of (18)FDG accumulation in the stomach, findings of upper
      gastrointestinal endoscopy, and Hp infection. The pattern of (18)FDG accumulation
      was classified into three groups: localized accumulation only in the fornix
      (Group A, 32 patients), diffuse accumulation throughout the entire stomach (Group
      B, 49 patients), and no accumulation (Group C, 191 patients). RESULTS: Regarding
      the relation between Hp infection and (18)FDG accumulation, Hp infection was
      positive in 56.3% of Group A, 73.5% of Group B, and 24.1% of Group C, with
      significant differences (p < 0.001). Regarding the relation between (18)FDG
      accumulation and gastric mucosal inflammation, when Groups A and B were compared
      with Group C, nearly half of the cases in the former groups had papular redness
      with a significantly higher frequency of redness and erosion. Three cases found
      to have malignant tumor were limited to the former groups. One MALT lymphoma case
      was also found in the same group. Accumulation of (18)FDG largely corresponded to
      mucosal inflammation including superficial gastritis and erosive gastritis, and
      therefore the main cause of non-specific (18)FDG accumulation was considered to
      be inflammatory mucosa (mainly redness). The accumulation pattern was not
      associated with atrophic changes of the gastric mucosa or with Hp infection, but
      with mucosal inflammatory changes, including redness and erosion localized to the
      fornix. CONCLUSIONS: Accumulation of (18)FDG in the stomach suggests a high
      probability of the presence of inflammatory change in the gastric mucosa forming
      a background for the development of cancer or malignant lymphoma, and thus
      requires further endoscopic examinations.

PMID- 19399580
TI  - Metallic artifacts caused by dental metal prostheses on PET images: a PET/CT
      phantom study using different PET/CT scanners.
AB  - OBJECTIVE: The objective of this study was to investigate the effects of computed
      tomography (CT) artifacts caused by dental metal prostheses on positron emission
      tomography (PET) images. METHODS: A dental arch cast was fixed in a cylindrical
      water-bath phantom. A spherical phantom positioned in the vicinity of the dental
      arch cast was used to simulate a tumor. To simulate the tumor imaging, the ratio
      of the (18)F-fluoro-deoxy-glucose radioactivity concentration of the spherical
      phantom to that of the water-bath phantom was set at 2.5. A dental bridge
      composed of a gold-silver-palladium alloy on the right mandibular side was
      prepared. A spherical phantom was set in the white artifact area on the CT images
      (site A), in a slightly remote area from the white artifact (site B), and in a
      black artifact area (site C). A PET/CT scan was performed with and without the
      metal bridge at each simulated tumor site, and the artifactual influence was
      evaluated on the axial attenuation-corrected (AC) PET images, in which the
      simulated tumor produced the strongest accumulation. Measurements were performed
      using three types of PET/CT scanners (scanners 1 and 2 with CT-based attenuation
      correction, and 3 with Cesium-137 ((137)Cs)-based attenuation correction). The
      influence of the metal bridge was evaluated using the change rate of the SUVmean
      with and without the metal bridge. RESULTS: At site A, an overestimation was
      shown (scanner 1: +5.0% and scanner 2: +2.5%), while scanner 3 showed an
      underestimation of -31.8%. At site B, an overestimation was shown (scanner 1:
      +2.1% and scanner 2: +2.0%), while scanner 3 showed an underestimation of -2.6%.
      However, at site C, an underestimation was shown (scanner 1: -25.0%, scanner 2: 
      32.4%, and scanner 3: -8.4%). CONCLUSIONS: When CT is used for attenuation
      correction in patients with dental metal prostheses, an underestimation of
      radioactivity of accumulated tracer is anticipated in the dark streak artifact
      area on the CT images. In this study, the dark streak artifacts of the CT caused
      by metallic dental prostheses may cause false negative finding of PET/CT in
      detecting small and/or low uptake tumor in the oral cavity.

PMID- 19399581
TI  - Pneumocystis jiroveci pneumonia as an atypical presentation of X-linked
      agammaglobulinemia.

PMID- 19399582
TI  - Phase II and pharmacokinetic study of thalidomide in Japanese patients with
      relapsed/refractory multiple myeloma.
AB  - To obtain approval from the Ministry of Health, Labor and Welfare of Japan, a
      phase II study was conducted to assess the pharmacokinetics and pharmacodynamics
      of thalidomide along with its efficacy and safety in Japanese patients with
      multiple myeloma. Between 2005 and 2006, 42 patients were enrolled, and 37
      patients met eligibility criteria. Of the 37 patients, 3 were excluded from
      efficacy analysis because of short duration of thalidomide administration (<4
      weeks). The overall response rate was 35.3% (12/34), including partial response
      of 14.7% (5/34) and minimal response of 20.6% (7/34). The adverse events observed
      in high frequency (>40%) were leukopenia, neutropenia, drowsiness, dry mouth, and
      constipation. Grade 3 neutropenia was observed in nine cases. Peripheral
      neuropathy and eruption were observed in about one-quarter of the patients. Deep
      vein thrombosis was not observed. At a single oral dose of thalidomide (100 mg),
      the C (max) was 1.68 +/- 0.41 microg/ml, T (max) was 4.54 +/- 1.71 h, T (1/2) was
      4.86 +/- 0.44 h, and AUC was 15.87 +/- 3.05 microg h/ml. Low-dose thalidomide was
      an effective and tolerable treatment for Japanese patients with
      relapsed/refractory myeloma. Leukopenia and neutropenia were the most serious
      adverse events. The pharmacokinetics was similar to those observed in Caucasian
      patients.

PMID- 19399583
TI  - Preoperative oral supplementation with carbohydrate and branched-chain amino acid
      enriched nutrient improves insulin resistance in patients undergoing a
      hepatectomy: a randomized clinical trial using an artificial pancreas.
AB  - Glucose metabolism is adversely affected in patients following major surgery.
      Patients may develop hyperglycemia due to a combination of surgical stress and
      postoperative insulin resistance. A randomized trial was conducted to elucidate
      the effect of preoperative supplementation with carbohydrates and branched-chain
      amino acids on postoperative insulin resistance in patients undergoing hepatic
      resection. A total of 26 patients undergoing a hepatectomy for the treatment of a
      hepatic neoplasm were randomly assigned to receive a preoperative supplement of
      carbohydrate and branched-chain amino acid-enriched nutrient mixture or not. The
      postoperative blood glucose level and the total insulin requirement for
      normoglycemic control during the 16 h following hepatic resection were determined
      using the artificial pancreas STG-22. Postoperative insulin requirements for
      normoglycemic control in the group with preoperative nutritional support was
      significantly lower than that in the control group (P = 0.039). There was no
      incidence of hypoglycemia (<40 mg/dL) observed in patients, including those with
      diabetes mellitus, when the STG-22 was used to control blood glucose levels. STG
      22 is a safe and reliable tool to control postoperative glucose metabolism and
      evaluate insulin resistance. The preoperative oral administration of carbohydrate
      and branched-chain amino acid-enriched nutrient is of clinical benefit and
      reduces postoperative insulin resistance in patients undergoing hepatic
      resection.

PMID- 19399584
TI  - Antizyme and antizyme inhibitor, a regulatory tango.
AB  - The polyamines are small basic molecules essential for cellular proliferation and
      viability. An autoregulatory circuit that responds to the intracellular level of
      polyamines regulates their production. In the center of this circuit is a family
      of small proteins termed antizymes. Antizymes are themselves regulated at the
      translational level by the level of polyamines. Antizymes bind ornithine
      decarboxylase (ODC) subunits and target them to ubiquitin-independent degradation
      by the 26S proteasome. In addition, antizymes inhibit polyamine transport across
      the plasma membrane via an as yet unresolved mechanism. Antizymes may also
      interact with and target degradation of other growth-regulating proteins. An
      inactive ODC-related protein termed antizyme inhibitor regulates polyamine
      metabolism by negating antizyme functions. The ability of antizymes to degrade
      ODC, inhibit polyamine uptake and consequently suppress cellular proliferation
      suggests that they act as tumor suppressors, while the ability of antizyme
      inhibitors to negate antizyme function indicates their growth-promoting and
      oncogenic potential.

PMID- 19399586
TI  - Intracellular protein degradation in mammalian cells: recent developments.
AB  - In higher organisms, dietary proteins are broken down into amino acids within the
      digestive tract but outside the cells, which incorporate the resulting amino
      acids into their metabolism. However, under certain conditions, an organism loses
      more nitrogen than is assimilated in the diet. This additional loss was found in
      the past century to come from intracellular proteins and started an intensive
      research that produced an enormous expansion of the field and a dispersed
      literature. Therefore, our purpose is to provide an updated summary of the
      current knowledge on the proteolytic machinery involved in intracellular protein
      degradation and its physiological and pathological relevance, especially
      addressed to newcomers in the field who may find further details in more
      specialized reviews. However, even providing a general overview, this is an
      extremely wide field and, therefore, we mainly focus on mammalian cells, while
      other cells will be mentioned only for comparison purposes.

PMID- 19399588
TI  - COX-1 is coupled with mPGES-1 and ABCC4 in human cervix cancer cells.
AB  - Cyclooxygenases are key enzymes in the arachidonic acid metabolism. Their
      unstable intermediate, prostaglandin H(2), is further metabolized to bioactive
      lipids by various downstream enzymes. In this study, utilizing short hairpin
      RNAs, we prepared a cell line of human cervix carcinoma with stable down
      regulated cyclooxygenase-1 (COX-1) to assess the impact of COX-1 reduction on the
      downstream enzymes. We found a significant microsomal prostaglandin E synthase-1
      (mPGES-1) suppression. In addition, mRNA expression of multidrug resistance
      protein 4 (MRP4, ABCC4), supposed to take part in antiviral and anticancer drug
      transport from cells, was up-regulated after COX-1 down-regulation. Our findings
      indicate that mPGES-1, believed to be coexpressed preferentially with
      cyclooxygenase-2, may be coupled to COX-1. ABCC4 up-regulation further supports
      the assumption of its involvement in prostanoid transport.

PMID- 19399587
TI  - Biogenesis of beta-barrel membrane proteins in bacteria and eukaryotes:
      evolutionary conservation and divergence.
AB  - Membrane-embedded beta-barrel proteins span the membrane via multiple amphipathic
      beta-strands arranged in a cylindrical shape. These proteins are found in the
      outer membranes of Gram-negative bacteria, mitochondria and chloroplasts. This
      situation is thought to reflect the evolutionary origin of mitochondria and
      chloroplasts from Gram-negative bacterial endosymbionts. beta-barrel proteins
      fulfil a variety of functions; among them are pore-forming proteins that allow
      the flux of metabolites across the membrane by passive diffusion, active
      transporters of siderophores, enzymes, structural proteins, and proteins that
      mediate protein translocation across or insertion into membranes. The biogenesis
      process of these proteins combines evolutionary conservation of the central
      elements with some noticeable differences in signals and machineries. This review
      summarizes our current knowledge of the functions and biogenesis of this special
      family of proteins.

PMID- 19399585
TI  - The human selenoproteome: recent insights into functions and regulation.
AB  - Selenium (Se) is a nutritional trace mineral essential for various aspects of
      human health that exerts its effects mainly through its incorporation into
      selenoproteins as the amino acid, selenocysteine. Twenty-five selenoprotein genes
      have been identified in humans and several selenoproteins are broadly classified
      as antioxidant enzymes. As progress is made on characterizing the individual
      members of this protein family, however, it is becoming clear that their
      properties and functions are quite diverse. This review summarizes recent
      insights into properties of individual selenoproteins such as tissue
      distribution, subcellular localization, and regulation of expression. Also
      discussed are potential roles the different selenoproteins play in human health
      and disease.

PMID- 19399590
TI  - A gel-forming poly-L: -guluronic acid produced from no guluronate-rich marine
      algae using new hydrolysis method: test for endovascular embolization.
AB  - To prepare a gel-forming poly-L-guluronic acid (Poly-G) from no guluronate-rich
      Laminaria japonica, a new hydrolysis method was employed with a lower HCl
      concentration (0.025-0.15 M) and a shorter treatment time (5 min). The Poly-Gs
      were set to measure purity, presence of poly-L-guluronic block, molecular weight
      distribution, polymer yield, viscosity, and compressive gel strength. Finally,
      the Poly-G was tested to embolize the renal vascular system by using a rabbit
      model and angiography. Optimized Poly-G could be selected with respect to wt%
      concentration, polymer yield, gel-forming stability, viscosity, and gel strength
      as an endovascular embolizing agent. Overall, 0.4-0.6% of 0.03 M-Poly-G obtained
      from acid treatment with 0.03 M of HCl had molecular weights greater than 80 kDa,
      and the best gelling capacity with an injectable viscosity (30-120 cP). It was
      successfully delivered into the vascular bed of a rabbit kidney and was shown
      angiographically to embolize the renal vascular system.

PMID- 19399589
TI  - The phosphorylation status of membrane-bound nucleoside diphosphate kinase in
      epithelia and the role of AMP.
AB  - Nucleoside diphosphate kinase (NDPK) has many roles and is present in different
      locations in the cell. Membrane-bound NDPK is present in epithelial fractions
      enriched for the apical membrane. Here, we show in human, mouse and sheep airway
      membranes, that the phosphorylation state of membrane-bound NDPK on histidine and
      serine residues differs dependent on many regulatory factors. GTP (but not ATP)
      promotes serine phosphorylation (pSer) of NDPK. Further we find that rising [AMP]
      promotes pSer (only with GTP) but inhibits histidine phosphorylation (pHis) of
      NDPK from both donors. We find that NDPK co-immunoprecipitates reciprocally with
      AMP-activated kinase and that these two proteins can co-localise in human
      airways. AMP concentrations rise rapidly when ATP is depleted or during hypoxia.
      We find that, in human airway cells exposed to hypoxia (3% oxygen), membrane
      bound NDPK is inhibited. Although histidine phosphorylation should in principle
      be independent of the nucleotide triphosphates used, we speculate that this
      membrane pool of NDPK may be able to switch function dependent on nucleotide
      species.

PMID- 19399591
TI  - Synthesis and characterisation of enhanced barrier polyurethane for encapsulation
      of implantable medical devices.
AB  - Polymeric membranes have been used as interfaces between implantable devices and
      biological tissues to operate as a protective barrier from water exchanging and
      to enhance biocompatibility. Polyurethanes have been used as biocompatible
      membranes for decades. In this study, copolymers of polyether urethane (PEU) with
      polydimethylsiloxane (PDMS) were synthesised with the goal of creating materials
      with low water permeability and high elasticity. PDMS was incorporated into
      polymer backbone as a part of the soft segment during polyurethane synthesis and
      physical properties as well as water permeability of resulting copolymer were
      studied in regard to PDMS content. Increase in PDMS content led to increase of
      microphase separation of the copolymer and corresponding increase in elastic
      modulus. Surface energy of the polymer was decreased by incorporating PDMS
      compared to unmodified PEU. PDMS in copolymer formed a hydrophobic surface which
      caused reduction in water permeability and water uptake of the membranes. Thus,
      PDMS containing polyurethane with its potent water resistant properties
      demonstrated a great promise for use as an implantable encapsulation material.

PMID- 19399592
TI  - Histopathologic study of rat connective tissue responses to maxillofacial
      silicone elastomers.
AB  - The aim of this histopathologic study was to assess and compare the subcutaneous
      connective tissue reaction to three different maxillofacial silicone elastomers
      (Cosmesil, Multisil, Episil). The test materials were directly inserted
      subcutaneously into the dorsal subcutaneous tissue of Wistar albino rats.
      Histopathological examinations were done at 7, 30, and 90 days after the
      implantation procedure. The presence of inflammation, presence of inflammatory
      giant cells, and the thickness of fibrous connective tissue adjacent to each
      inserted sample were recorded. Data was evaluated by analysis of variance,
      Wilcoxon signed ranks test and Kruskal Wallis test. Cosmesil, Multisil and Episil
      silicone elastomers at 7 days elicited a severe inflammatory reaction. However,
      these reactions decreased by the 30 and 90 days. All silicone elastomers elicited
      a moderate inflammatory reaction at 30 and 90 days. There were no significant
      differences in tissue reaction between the materials at 7, 30, and 90 days (P >
      0.05). All the maxillofacial silicone elastomers evaluated can not be assigned a
      favorable biocompatibility level based on this study's histologic findings.

PMID- 19399593
TI  - Multifunctional implant coatings providing possibilities for fast antibiotics
      loading with subsequent slow release.
AB  - The possibility to fast-load biomimetic hydroxyapatite coatings on surgical
      implant with the antibiotics Amoxicillin, Gentamicin sulfate, Tobramycin and
      Cephalothin has been investigated in order to develop a multifunctional implant
      device offering sustained local anti-bacterial treatment and giving the surgeon
      the possibility to choose which antibiotics to incorporate in the implant at the
      site of surgery. Physical vapor deposition was used to coat titanium surfaces
      with an adhesion enhancing gradient layer of titanium oxide having an amorphous
      oxygen poor composition at the interface and a crystalline bioactive anatase
      TiO(2) composition at the surface. Hydroxyapatite (HA) was biomimetically grown
      on the bioactive TiO(2) to serve as a combined bone in-growth promoter and drug
      delivery vehicle. The coating was characterized using scanning and transmission
      electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The
      antibiotics were loaded into the HA coatings via soaking and the subsequent
      release and antibacterial effect were analyzed using UV spectroscopy and
      examination of inhibition zones in a Staphylococcus aureus containing agar. It
      was found that a short drug loading time of 15 min ensured antibacterial effects
      after 24 h for all antibiotics under study. It was further found that the release
      processes of Cephalothin and Amoxicillin consisted of an initial rapid drug
      release that varied unpredictably in amount followed by a reproducible and
      sustained release process with a release rate independent of the drug loading
      times under study. Thus, implants that have been fast-loaded with drugs could be
      stored for ~10 min in a simulated body fluid after loading to ensure
      reproducibility in the subsequent release process. Calculated release rates and
      measurements of drug amounts remaining in the samples after 22 h of release
      indicated that a therapeutically relevant dose could be achieved close to the
      implant surface for about 2 days. Concluding, the present study provides an
      outline for the development of a fast-loading slow-release surgical implant kit
      where the implant and the drug are separated when delivered to the surgeon, thus
      constituting a flexible solution for the surgeon by offering the choice of quick
      addition of antibiotics to the implant coating based on the patient need.

PMID- 19399594
TI  - Growth of outgrowth endothelial cells on aligned PLLA nanofibrous scaffolds.
AB  - Tissue engineering holds great promise in providing vascular grafts as
      substitutes for damaged small-diameter blood vessels. Two of the key factors in
      vascular tissue engineering are biocompatible scaffolds that mimic the effects of
      extracellular matrix and the source of seeding cells. Synthetic poly-L-lactic
      acid (PLLA) nanofibers has been shown to be excellent scaffolds for tissue
      engineering. Outgrowth endothelial cells (OECs) isolated from human peripheral
      blood could also be expanded in vitro and stably maintain the differentiated
      phenotypes and could be used as the seeding cells for engineering autologous
      vascular crafts. Here we tested the possibility of combining these two together.
      We found that PLLA nanofibers are not only biocompatible with OECs originally
      isolated from rabbit peripheral blood, the aligned PLLA fibers actually promoted
      and guided their sustained proliferation. These results suggest that aligned PLLA
      could be excellent both as the scaffolds and as a promoter of cell growth during
      vascular tissue engineering.

PMID- 19399596
TI  - The Fluorescence Study of Interaction Between Bovine Serum Albumin and
      Polyacrylic Acid.
AB  - The complex formation of Bovine Serum Albumin (BSA) with anionic polyelectrolyte
      (polyacrylic acid, PAA) in aqueous solution was studied by a fluorescence
      technique, pH titration and HPLC analysis. The character of the interactions and
      solubility of the polycomplex particles depends on the BSA/PAA ratios and the pH
      of solution. The interaction at pH > pI (isoelectric point of BSA) (pH 6.0-7.0)
      is negligible weak and at pH 5.0 results with the formation of stable water
      soluble polycomplexes at a wide range of protein/polymer ratios. The fluorescence
      intensity of BSA sharply decreased when an different amount of PAA was added and
      its maximum wavelength shifts towards the blue region. The protein molecules in
      the structure of soluble polycomplex particles are densely covered by the shelf
      of a polymer coil and practically "fenced off" from the water environment. This
      effect was reinforced by the increase of protein components. Existence of soluble
      and insoluble PAA-BSA complexes have been observed at pH < pI (pH 4.0-4.3). These
      soluble complexes characterized by the structure of particles in which protein
      molecules are densely covered by the shelf of a polymer coil. By the increase in
      the protein concentration, these complexes aggregate to an interpolymer species.

PMID- 19399595
TI  - Luminescent donor-acceptor beta-diketones: modulation of emission by solvent
      polarity and group II metal binding.
AB  - A class of aryl trifluoromethyl-containing beta-diketones were synthesized via
      one step Claisen condensation. These pi-conjugated diketones exhibit strong
      solvatochromism from intramolecular donor-acceptor charge transfer (CT). In
      addition, fluorescence quantum yields (phi(f)) and lifetimes (tau(f)) were
      measured in different solvents. Diketones exhibit bathochromic shifts in emission
      spectra with increasing solvent polarity. Fluorescence changes upon Group II
      metal binding were also studied. Despite the relatively simple structure, the
      anthracene-CF(3) diketone, atm, has strong binding affinity for Mg2+. A 70 nm
      blue shift and sixfold increase in intensity were observed upon addition of only
      one equivalent MgCl2 in ethanol solution. It also shows selectivity for Mg2+
      binding even in the presence of excess Ca2+. Association constant (Ka)
      calculations suggest atm has two orders of magnitude stronger chelation for
      divalent magnesium than for calcium. These findings make atm an attractive
      starting point for molecular probe and light emitting material design.

PMID- 19399599
TI  - A time series modeling approach in risk appraisal of violent and sexual
      recidivism.
AB  - For over half a century, various clinical and actuarial methods have been
      employed to assess the likelihood of violent recidivism. Yet there is a need for
      new methods that can improve the accuracy of recidivism predictions. This study
      proposes a new time series modeling approach that generates high levels of
      predictive accuracy over short and long periods of time. The proposed approach
      outperformed two widely used actuarial instruments (i.e., the Violence Risk
      Appraisal Guide and the Sex Offender Risk Appraisal Guide). Furthermore, analysis
      of temporal risk variations based on specific time series models can add valuable
      information into risk assessment and management of violent offenders.

PMID- 19399597
TI  - Post-translational modifications of ATP synthase in the heart: biology and
      function.
AB  - The ATP synthase complex is a critical enzyme in the energetic pathways of cells
      because it is the enzyme complex that produces the majority of cellular ATP. It
      has been shown to be involved in several cardiac phenotypes including heart
      failure and preconditioning, a cellular protective mechanism. Understanding the
      regulation of this enzyme is important in understanding the mechanisms behind
      these important phenomena. Recently there have been several post-translational
      modifications (PTM) reported for various subunits of this enzyme complex, opening
      up the possibility of differential regulation by these PTMs. Here we discuss the
      known PTMs in the heart and other mammalian tissues and their implication to
      function and regulation of the ATP synthase.

PMID- 19399600
TI  - Is manipulative intent necessary to mitigate the eyewitness post-identification
      feedback effect?
AB  - Feedback suggestive of mistaken eyewitnesses claiming that they identified the
      correct person leads to distorted retrospective judgments of certainty, view, and
      other testimony-relevant measures. This feedback effect can be significantly
      mitigated if witnesses later learn that the feedback source did not know which
      lineup member was the correct person and had a manipulative intent (post-feedback
      suspicion manipulation). We replicated the post-feedback suspicion effect and
      used a mistake condition showing that the manipulative intent is not a necessary
      component, thereby ruling out reactance-type interpretations of the post-feedback
      suspicion effect. Some conditions included instructions to ensure relevant
      processing of the feedback before the post-feedback suspicion manipulations, but
      these processing instructions did not mitigate the effect. The results suggest
      that these retrospective judgments (e.g., certainty, attention, view) remain
      malleable as new information unfolds.

PMID- 19399598
TI  - Mitochondrial dynamics in heart cells: very low amplitude high frequency
      fluctuations in adult cardiomyocytes and flow motion in non beating Hl-1 cells.
AB  - The arrangement and movement of mitochondria were quantitatively studied in adult
      rat cardiomyocytes and in cultured continuously dividing non beating (NB) HL-1
      cells with differentiated cardiac phenotype. Mitochondria were stained with
      MitoTracker Green and studied by fluorescent confocal microscopy. High speed
      scanning (one image every 400 ms) revealed very rapid fluctuation of positions of
      fluorescence centers of mitochondria in adult cardiomyocytes. These fluctuations
      followed the pattern of random walk movement within the limits of the internal
      space of mitochondria, probably due to transitions between condensed and orthodox
      configurational states of matrix and inner membrane. Mitochondrial fusion or
      fission was seen only in NB HL-1 cells but not in adult cardiomyocytes. In NB HL
      1 cells, mitochondria were arranged as a dense tubular network, in permanent
      fusion, fission and high velocity displacements of approximately 90 nm/s. The
      differences observed in mitochondrial dynamics are related to specific structural
      organization and mitochondria-cytoskeleton interactions in these cells.

PMID- 19399601
TI  - The profile of prostate epithelial cytokines and its impact on sera prostate
      specific antigen levels.
AB  - The aim of this study was determined the expression of pro inflammatory cytokines
      in prostate epithelial cells. Furthermore, we analysed the relation between these
      cytokines and sera PSA levels according the three groups: 0-4, 4-20 and >20
      ng/mL. The study was carried out in five normal prostate (NP), 27 benign prostate
      hyperplastic (BPH) and 18 prostate cancer (PC). Immunohistochemical and Western
      blot analysis was performed. Serum levels of PSA were assayed by Immulite
      autoanalyser. The western Blotting analysis revealed an immunoexpression of IL
      1alpha, IL-6 and TNFalpha in BPH and PC. IL-1alpha, was absent in NP.
      Immunohistochemical analysis showed significant high optical density to IL-1alpha
      and IL-6 in cancer epithelial cells (19.45 +/- 3.25 and 26.2 +/- 3.19) compared
      to normal cells (1.73 +/- 1.51 and 4.83 +/- 2.65). While, TNFalpha optical
      densities were not significant in NP (12.03 +/- 2.9), BPH (9.87 +/- 3.85) and PC
      (13.34 +/- 2.34). The different profiles of cytokines according sera PSA levels
      showed a high immunoexpression of the profile (IL-6+, IL-1alpha+) in BPH patients
      with PSA between 0-4 and 4-20 ng/mL. However, PC patients with sera PSA between 4
      and 20 ng/mL, showed a significant high immunoexpression of the profile (IL-6+,
      IL-1alpha-). This data demonstrate a locally production of pro-inflammatory
      cytokines by prostate epithelial cells and a cross talk between PSA and these
      cytokines in prostate pathologies.

PMID- 19399602
TI  - Electrophysiology of papillary muscle in SAH: changes and N-acetylcysteine
      protection.
AB  - BACKGROUND: Although subarachnoid hemorrhage (SAH) serves as a good model to
      study heart-brain interactions, neither the changes on the single ventricular
      action potential (SVAP) and contraction nor the effects of possible
      cardioprotective agents have been investigated. MATERIALS AND METHODS: A total of
      18 male rabbits were used for the three experimental groups. SAH was induced by
      replacing the cerebrospinal fluid (CSF) with fresh autologous blood at the ratio
      of 1 mL to the 1-kg body mass (N = 6). In the control (CON; N = 6) group, the CSF
      was replaced with serum physiologic at the same ratio. The treated SAH group
      (SAH+NAC) received daily intraperitoneal N-acetylcysteine (NAC; 150 mg/kg for 3
      days) starting from just before SAH was induced by CSF replacement. On the fourth
      day, animals were examined for the single action potential and contraction
      recordings from the left ventricular papillary muscle. RESULTS: At the end of 3
      days, the overshoot decreased together with increased time to reach the peak
      potential. Additionally, the resting membrane potential was depressed and
      repolarization was slowed during SVAPs. On the other hand, peak tension depressed
      and time to peak increased. NAC treatment, which protects infarction in the
      brain, prevented these pathological changes in the cardiac muscle. CONCLUSION:
      SAH-induced cardiac changes can be attributed to adenosine triphosphate depletion
      through mitochondrial dysfunction. Pretreatment of NAC to SAH on the other hand
      had a positive effect on these cardiac changes. But the exact mechanism by which
      NAC treatment protects the cardiac muscle needs further investigation.

PMID- 19399603
TI  - Efficient computation of the maximum a posteriori path and parameter estimation
      in integrate-and-fire and more general state-space models.
AB  - A number of important data analysis problems in neuroscience can be solved using
      state-space models. In this article, we describe fast methods for computing the
      exact maximum a posteriori (MAP) path of the hidden state variable in these
      models, given spike train observations. If the state transition density is log
      concave and the observation model satisfies certain standard assumptions, then
      the optimization problem is strictly concave and can be solved rapidly with
      Newton-Raphson methods, because the Hessian of the loglikelihood is block
      tridiagonal. We can further exploit this block-tridiagonal structure to develop
      efficient parameter estimation methods for these models. We describe applications
      of this approach to neural decoding problems, with a focus on the classic
      integrate-and-fire model as a key example.

PMID- 19399604
TI  - Brief report: Visual processing of faces in individuals with fragile X syndrome:
      an eye tracking study.
AB  - Gaze avoidance is a hallmark behavioral feature of fragile X syndrome (FXS), but
      little is known about whether abnormalities in the visual processing of faces,
      including disrupted autonomic reactivity, may underlie this behavior. Eye
      tracking was used to record fixations and pupil diameter while adolescents and
      young adults with FXS and sex- and age-matched typically developing controls
      passively viewed photographs of faces containing either a calm, happy, or fearful
      expression, preceded by a scrambled face matched on luminance. Results provide
      quantitative evidence for significant differences in gaze patterns and increased
      pupillary reactivity when individuals with FXS passively view static faces. Such
      abnormalities have significant implications in terms of understanding causes of
      gaze avoidance observed in individuals with FXS.

PMID- 19399605
TI  - Latina mother-daughter dyads: relations between attachment and sexual behavior
      under the influence of alcohol or drugs.
AB  - Associations among mother-daughter attachment, mother and daughter substance
      abuse, and daughter's sexual behavior under the influence of drugs and alcohol
      were investigated among 158 adult U.S. Latina daughters. Latina daughters were
      sampled from four mother-daughter dyad types: substance abusing mother and
      daughter, substance abusing mother only, substance abusing daughter only, and non
      substance-abusing mother and daughter. Substance abusing daughters with substance
      abusing mothers, and daughters who were less strongly attached to their mothers,
      reported more sex under the influence of drugs. Age, marital status, substance
      abuse, and mother's substance abuse all influenced the daughter's sex under the
      influence of alcohol. An unexpected positive association between attachment and
      sex under the influence of alcohol was found for daughters who were more closely
      attached to a substance abusing mother. Implications for future research, and
      HIV/AIDS and drug prevention and treatment programs for Latinas are discussed.

PMID- 19399606
TI  - Revisiting practice-based research networks as a platform for mental health
      services research.
AB  - Practice-based research networks (PBRNs)-collaborations of practice settings that
      work together to generate research knowledge-are underused in mental health
      services research. This article proposes an agenda for mental health services
      research that uses a variety of PBRN structures and that focuses on what really
      happens in practice, the effectiveness of practice innovations in real world
      care, the challenges of implementing evidence supported interventions,
      modification of clinician behavior, and assessment of the effect of mental health
      policy changes on practice. The challenges of conducting research within PBRNs
      are substantial, including difficulties in maintaining positive member relations,
      securing ongoing funding, sustaining productivity, overcoming IRB entanglements
      and achieving both scientific excellence in recruitment and measurement validity
      and utility for practitioner members. However, the awareness of these challenges
      allows researchers and practitioners to build networks that creatively overcome
      them and that infuse mental health services research with heavy doses of the
      realities of everyday clinical practice.

PMID- 19399607
TI  - Chemical characterization of Pax6-immunoreactive periglomerular neurons in the
      mouse olfactory bulb.
AB  - The Pax6 transcription factor is a key element along brain development in both
      the visual and olfactory systems. The involvement of Pax6 in neural fate is well
      documented in the visual system, whereas in the olfactory system, and in
      particular in the olfactory bulb (OB), its expression during adulthood has only
      begun to be elucidated. In the OB, the modulation of primary sensory information
      is first performed by periglomerular cells (PG). A considerable body of
      information has unveiled the neurochemical heterogeneity of these neurons. Thus
      it is well known that Pax6 coexists with dopaminergic/GABAergic mouse PG.
      However, the presence of this transcription factor in other mouse PG
      subpopulations has not been studied. Here, we analyzed whether Pax6 is expressed
      in PG containing the calcium-binding proteins neurocalcin and parvalbumin, and
      the neuropeptide cholecystokinin. Our results show that Pax6 is not expressed by
      these PG subpopulations, suggesting that it is mainly restricted to GABAergic PG
      populations. These findings provide new data in the chemical characterization of
      mouse Pax6-positive PG.

PMID- 19399608
TI  - Soft budget constraints in China: evidence from the Guangdong hospital industry.
AB  - Using data from 276 general acute hospitals in the Pearl River Delta region of
      Guangdong Province from 2002 and 2004, we construct a preliminary metric of
      budget constraint softness. We find that, controlling for hospital size,
      ownership, and other factors, a Chinese hospital's probability of receiving
      government financial support is inversely associated with the hospital's previous
      net revenue, an association consistent with soft budget constraints.

PMID- 19399609
TI  - Development of resistance to cyfluthrin and naphthalene among Daphnia magna.
AB  - In this study, Daphnia magna were exposed to a pyrethroid insecticide
      (cyfluthrin) or a polycyclic aromatic hydrocarbon (naphthalene) for 12
      generations to evaluate development of resistance followed by a 12 generation
      recovery period. Twenty-four hour old D. magna were exposed to concentrations of
      each chemical resulting in 50-70% mortality to select for the least sensitive
      individuals. LC50 values, survival, reproductive output, and time to first brood
      in stressor-exposed and control D. magna were recorded for each generation.
      Significant changes in LC50 values were observed after 4 generations and then
      declined after 6-10 generations post-exposure. D. magna were 5 times less
      sensitive to cyfluthrin and 3 times less sensitive to naphthalene as compared to
      controls after 12 generations of exposure. There were no differences in survival,
      time to first brood, or total number of offspring produced between control and
      either of the resistant F13 D. magna. Cyfluthrin exposed D. magna exhibited cross
      resistance to DDT and methyl parathion, and naphthalene resistant D. magna were
      less sensitive than controls to both pyrene and benz(a)anthracene. When the
      cytochrome P450 inhibitor piperonyl butoxide was used in conjunction with
      cyfluthrin and naphthalene the sensitivity of resistant and control D. magna were
      equal, suggesting P450s were responsible for conveying resistance. This study
      demonstrates that life history and organisms' capacity to develop resistance is
      important to consider ensuring accuracy of ecological risk assessments.

PMID- 19399610
TI  - Sensitivity of preparasitic stages of Chordodes nobilii (Gordiida, Nematomorpha)
      to malathion.
AB  - The largest part of the life cycle of Gordiida, known as horsehair worms, occurs
      in aquatic environments usually affected by agricultural activities. The free
      living adults reproduce in freshwater environments, where preparasitic larvae
      undergo development. Since malathion is an insecticide used in the distribution
      area of Chordodes nobilii, the aim of this study is to evaluate the effect of
      malathion concentrations which might be expected in the environment on
      preparasitic stages of this species. The embryonic development and the viability
      of larvae were analyzed after a short-term exposure to malathion concentrations
      ranging between 36 and 220 microg a.i./l. Embryo development was inhibited at 220
      microg a.i./l and the infective capacity of larvae derived from malathion-exposed
      eggs was significantly decreased starting from the lowest concentration. Larvae
      developed from malathion-exposed eggs exhibited malformations. Directly exposed
      larvae also showed decreased infectivity since the lowest assayed concentration.
      Our results indicate that a short-term exposure to malathion at levels
      potentially present in the surface water in environments inhabited by Chordodes
      nobilii affects significantly its preparasitic stages and the infective capacity
      of parasitic larvae.

PMID- 19399611
TI  - The human G93A-superoxide dismutase-1 mutation, mitochondrial glutathione and
      apoptotic cell death.
AB  - Mutations in Cu/Zn superoxide dismutase are a cause of motor neuron death in
      about 20% of cases of familial amyotrophic lateral sclerosis (ALS). Although the
      molecular mechanism of which these mutations induce motor neuron cell death is to
      a large extent unknown, there is significant evidence that effects on
      mitochondrial function and development of oxidative stress make a major
      contribution to the selective death of motor neurons in this disease. In this
      overview article we review the current understanding of mutant SOD1-mediated
      motor neuron degeneration in ALS with focus on oxidative damage and mitochondrial
      dysfunction. We also present novel information on the role of mitochondrial
      glutathione for the survival of NSC-34 cells stably transfected with the human
      SOD1(G93A) mutation, putting forward the hypothesis that this antioxidant pool
      provides a potentially useful target for therapeutic intervention.

PMID- 19399612
TI  - Proteasome inhibitor MG132 inhibits angiogenesis in pancreatic cancer by blocking
      NF-kappaB activity.
AB  - Since angiogenesis enables solid tumors, including pancreatic cancer (PaCa), to
      grow and metastasize, the development of anti-angiogenic agents is currently one
      of the urgent issues. Proteasome inhibitors are well known for inhibiting nuclear
      factor-kappa B (NF-kappaB) activity in various cancer cells, but little is known
      about their biologic mechanisms against angiogenesis in PaCa. We divided human
      PaCa cell lines into high-angiogenic (BxPC-3 and SW 1990) and low-angiogenic (MIA
      PaCa-2 and Capan-2) groups. The high-angiogenic PaCa cell lines constitutively
      expressed high NF-kappaB activity and produced high levels of vascular
      endothelial growth factor (VEGF) and interleukin 8 (IL-8). The conditioned media
      from BxPC-3 significantly enhanced both proliferation of and tube formation by
      human umbilical vein endothelial cells (HUVECs) and these enhancements were
      significantly inhibited by the proteasome inhibitor MG132 treatment.
      Collectively, MG132 blocked PaCa-derived VEGF and IL-8 production through
      inhibition of NF-kappaB activity. Thus, proteasome inhibitors may prove
      beneficial as anti-angiogenic therapy for PaCa. Our studies show that MG132, a
      proteasome inhibitor, significantly blocked pancreatic-cancer-associated
      angiogenesis through inhibition of NF-kappaB and NF-kappaB-dependent
      proangiogenic gene products VEGF and IL-8.

PMID- 19399613
TI  - A comparison of antibody testing, permeability testing, and zonulin levels with
      small-bowel biopsy in celiac disease patients on a gluten-free diet.
AB  - Active celiac disease is associated with positive endomysial (EMA) and tissue
      transglutaminase (TTG) antibodies, elevated zonulin levels, and increased
      intestinal permeability. There is little known about what happens to these
      immunologic and structural abnormalities in patients on a gluten-free diet and
      their correlation with small-bowel biopsy changes. Adult patients previously
      diagnosed with celiac disease and on a gluten-free diet for greater than 1 year
      were considered for the study. All patients underwent the following: measurement
      of EMA and TTG antibodies, serum zonulin levels, intestinal permeability (IP)
      testing with lactulose/mannitol ratios, food diary analysis for gluten ingestion
      and small- bowel biopsy. A total of 21 patients on a gluten-free diet for a mean
      of 9.7 years completed the study. There were ten patients who had normalization
      of intestinal biopsies, IP and TTG, and EM antibodies. Six patients had Marsh
      type 2 or 3 lesions and all had either abnormal IP (5/6) or TTG antibody (4/6).
      In patients with Marsh type 3 lesions, there was a correlation between IP and
      zonulin levels. A subgroup of patients with celiac disease on a gluten-free diet
      has complete normalization of intestinal biopsies, intestinal permeability
      defects, and antibody levels. Patients with Marsh type 3 lesions have abnormal
      TTG antibodies and intestinal permeability with zonulin levels that correlate
      with IP. These abnormalities may be due to continued gluten ingestion. Further
      study is needed to determine the clinical utility of TTG antibodies and IP
      testing in following patients with celiac disease.

PMID- 19399614
TI  - Molecular biomarkers correlate with disease-free survival in patients with anal
      canal carcinoma treated with chemoradiation.
AB  - Large primary tumor and clinical nodal involvement in patients with anal
      carcinoma treated with chemoradiation are associated with poor disease-free
      survival (DFS). However, the outcome in individual patient is unpredictable. We
      hypothesized that biomarkers related to chemotherapy and/or radiation resistance
      would be associated with DFS. We analyzed clinical and biomarker data in 30
      patients with anal carcinoma who had chemoradiation. Patient selection was based
      on the availability of untreated cancer for biomarkers, completion of prescribed
      chemoradiation, and patient outcomes (~50% disease-free) nonrepresentative of
      published cohorts but conducive to biomarker discovery. Ten biomarkers, Ki67,
      human telomerase (hTERT), epidermal growth factor receptor (EGFR), p53, p16, Bcl
      2, vascular endothelial growth factor (VEGF), nuclear factor kappa-B (NF-kappaB),
      SHH, and Gli-1, were studied. Raw data as continuous variable (only EGFR was
      trichotomized) were analyzed. Univariate and multivariate Cox models were
      utilized to assess relationship between DFS and biomarkers. Twenty-three of 30
      patients were women, tumor diameter was >5 cm in 30, and 37% had clinically
      positive nodes. Fourteen (30%) patients had a DFS event after chemoradiation. In
      univariate analysis, NF-kappaB (P = 0.01), SHH (P = 0.02), Gli-1 (P = 0.02), and
      tumor diameter (P = 0.03) were significantly associated with DFS, and Ki67 (P =
      0.07) was marginally significant. In multivariate analysis, tumor diameter (P =
      0.003), Ki67 (P = 0.005), NF-kappaB (P = 0.002), SHH (P = 0.02), and Gli-1 (P =
      0.02) were significantly associated with DFS. Our data, albeit preliminary,
      suggest that several biomarkers (Ki67, NF-kappaB, SHH, and Gli-1) are associated
      with DFS. Upon further expansion and validation, these results may provide a
      biomarker-based understanding of heterogeneous clinical biology of patients with
      anal carcinoma.

PMID- 19399615
TI  - Obesity is associated with an increased prevalence of advanced adenomatous colon
      polyps in a male veteran population.
AB  - Obesity has been associated with an increased risk for colonic adenomatous polyps
      (APs) and colorectal cancers, but the influence of obesity on the development of
      advanced APs is not clear. The purpose of this study is to determine the
      influence of obesity on the prevalence of advanced APs in a male veteran
      population. We performed a retrospective study of patients (n = 2,903) with
      histologically confirmed APs on an index colonoscopy. APs were evaluated for
      advanced features (size > or = 1 cm in diameter and/or a villous component and/or
      high grade dysplasia). Patients were categorized as: normal weight (BMI > 18.5
      and < 25), overweight (BMI > or = 25 and < 30), and obese (BMI > or = 30). An
      association between clinical factors and advanced APs was sought by Kruskal
      Wallis test and Pearson Chi-square. Multiple logistic regression analysis was
      used to determine independent predictors for advanced APs. We identified 2,903
      male patients with APs (mean age 64 + 1.1(SE) years; 770 (27%) normal weight,
      1,029 (35%) overweight, 1,104 (38%) obese. By univariate analysis, obese patients
      had a greater prevalence of advanced APs than the overweight and normal weight
      patients (28 vs. 23 vs. 24%, p = 0.025). Multiple logistic regression analysis
      confirmed the association of obesity and advanced APs (OR = 1.01, CI = 1-1.02, p
      = 0.04). For every one-unit increase in BMI above 30, there was a corresponding
      1% increase in the frequency of finding advanced APs. Obesity in male veteran
      patients is associated with the finding of advanced APs on colonoscopy. We
      speculate that obesity may increase the risk for CRC by promoting the development
      of advanced APs.

PMID- 19399616
TI  - Upregulation and CpG island hypomethylation of the TRF2 gene in human gastric
      cancer.
AB  - The telomere-binding protein TRF2 regulates both telomere protection and telomere
      length. The fact that TRF2 is up-regulated in some tumors indicates that TRF2
      plays a role in cancer. However, the role of TRF2 in gastric cancer has not been
      fully understood. The aim of this study is to evaluate the expression pattern of
      TRF2 in gastric cancer and examine the potential mechanism of TRF2 regulation.
      Our study revealed that the expression of TRF2 analyzed by immunohistochemistry
      was significantly higher in gastric cancers compared to noncancerous tissues.
      Moreover, TRF2 methylation was detected in six of 30 (20%) primary gastric
      cancers and 18 of 30 (60%) paired normal tissues, and the downregulation of TRF2
      was strongly correlated with the methylation status (P < 0.001). Our results
      suggest that hypomethylation might contribute to the upregulation of TRF2 in
      gastric cancers and this overexpression may play a role in the pathogenesis of
      gastric cancers.

PMID- 19399617
TI  - Melatonin modulates the severity of taurocholate-induced acute pancreatitis in
      the rat.
AB  - The aim of this study was to investigate the effects of melatonin on serum
      amylase, tumor necrosis factor-alpha (TNF-alpha) and histological changes in rats
      with taurocholate-induced acute pancreatitis. Thirty male Wistar rats were
      randomly divided into three groups; group 1, group 2 and group 3 were enrolled as
      melatonin, control and sham groups, respectively (n = 10 per group). Acute
      pancreatitis was induced by 1 ml/kg body weight using 5% taurocholate injection
      into the biliopancreatic duct in groups 1 and 2 after clamping the hepatic duct.
      Those in group 1 received 50 mg/kg body weight melatonin by intraperitoneal
      (i.p.) injection. Group 2 received physiological saline i.p. at the same dose.
      Group 3 solely underwent laparotomy with cannulation of the biliopancreatic duct.
      Twenty-four hours after the intervention, the rats were killed, and serum samples
      were collected to measure amylase and TNF-alpha levels. Simultaneously,
      pancreatic tissues were removed, stained with hematoxylin-eosin and examined
      under a light microscope. Serum amylase and TNF-alpha levels were significantly
      lower in the melatonin group compared to the controls (P < 0.001). The total
      histological score, including edema, inflammation, perivascular infiltrate,
      acinar necrosis, fat necrosis and hemorrhage, was also significantly lower in the
      melatonin group as compared to the control (P < 0.0001). In conclusion, melatonin
      is potentially capable of reducing pancreatic damage by decreasing serum TNF
      alpha levels in taurocholate-induced acute pancreatitis in rats. This result
      supports the idea that melatonin might be beneficial in ameliorating the severity
      of acute pancreatitis.

PMID- 19399618
TI  - Secular trends in hospitalization for IBD: the ecological niche.

PMID- 19399619
TI  - African Americans may differ in their reasons for declining hepatitis C therapy
      compared to non-African Americans.

PMID- 19399620
TI  - Meloxicam as a cause of drug-induced autoimmune hepatitis.

PMID- 19399621
TI  - Pneumonitis as a consequence of (peg)interferon-ribavirin combination therapy for
      hepatitis C: a review of the literature.
AB  - Combination of peginterferon and ribavirin is the current therapy for chronic
      hepatitis C infection (HCV). Interstitial pneumonitis is a rare side-effect of
      HCV therapy and is an important cause of dose reduction or discontinuation,
      impairing success of antiviral therapy. We performed a review of the literature
      in order to present diagnostic modalities and possible treatments for pneumonitis
      and to offer guidelines. We searched for cases where pneumonitis as a side-effect
      of HCV treatment was documented. First we performed a literature search via
      PubMed and Web of Science interface and second we searched three drug toxicity
      databases. We systematically analyzed all case reports with respect to clinical
      manifestations, type of treatment, and outcome. A literature search revealed 19
      articles, containing 25 case descriptions, while we traced 33 cases from the drug
      toxicity databases. Pneumonitis presented with any of the combination of fever,
      dyspnea, and cough and can arise with any type of (conventional or pegylated)
      interferon. Mortality secondary to pneumonitis was seen in 7% of cases,
      exclusively with peginterferon alpha-2b. In most cases therapy was discontinued
      and steroids were started. Interferon-induced pneumonitis during HCV treatment is
      a severe complication and should be recognized in order to prevent further
      pulmonary damage and/or death.

PMID- 19399622
TI  - Acculturation, familism and mother-daughter relations among suicidal and non
      suicidal adolescent Latinas.
AB  - We examined the role of acculturation, familism and Latina mother-daughter
      relations in suicide attempts by comparing 65 adolescents with recent suicide
      attempts and their mothers to 75 teens without any attempts and their mothers.
      Attempters and non-attempters were similar in acculturation and familistic
      attitudes but attempters report significantly less mutuality and communication
      with their mothers than non-attempters. Mothers of attempters reported lower
      mutuality and communication with their daughters than mothers of non-attempters.
      Small increments in mutuality decreased the probability of a suicide attempt by
      57%. Acculturation and familism do not appear to play major roles in suicide
      attempts but relational factors may. Instituting school-based psychoeducational
      groups for young Latinas, particularly in middle school, and their parents,
      separately and jointly, and focusing on raising effective communication and
      mutuality between parents and adolescent daughters are important primary
      prevention strategies.

PMID- 19399623
TI  - Syllabic effects in Italian lexical access.
AB  - Two cross-modal priming experiments tested whether lexical access is constrained
      by syllabic structure in Italian. Results extend the available Italian data on
      the processing of stressed syllables showing that syllabic information restricts
      the set of candidates to those structurally consistent with the intended word
      (Experiment 1). Lexical access, however, takes place as soon as possible and it
      is not delayed till the incoming input corresponds to the first syllable of the
      word. And, the initial activated set includes candidates whose syllabic structure
      does not match the intended word (Experiment 2). The present data challenge the
      early hypothesis that in Romance languages syllables are the units for lexical
      access during spoken word recognition. The implications of the results for our
      understanding of the role of syllabic information in language processing are
      discussed.

PMID- 19399624
TI  - Nietzche's echo--a dialogue with Thomas Altizer.
AB  - Prophets provoke psychological unrest, especially when exposing accepted beliefs
      as profound deceptions. The biblical prophets exemplify such confrontation as do
      certain atheists ardently opposed to the images of God created by those seers.
      The German philosopher Friedrich Nietzsche dramatically illustrates this type of
      counterforce to the Judeo-Christian tradition. His prophet Zarathustra is
      intended to be a model for the modern mind, one free of superstitions inflicted
      by antiquated religious dogma. Nietzsche's credo "God is dead" served as a
      declaration for the nineteenth century. In the twentieth century, it became a
      theological diagnosis. As a "movement," or "tenor," the death of God or radical
      theology was spearheaded by Thomas Altizer, a well-published young professor
      center-staged during the turbulent 1960s. His work foreshadows a new strain of
      atheism currently represented by biologist Richard Dawkins (2006, The God
      delusion. New York: Houghton Mifflin), philosopher Daniel Dennett (2006, Breaking
      the spell. New York: Penquin), neuroscientist Sam Harris (2004, The end of faith.
      New York: W.W. Norton; 2008, Letter to a Christian nation. New York: Vintage),
      journalist Christopher Hitchens (2007, God is not great. New York: Twelve), and
      mathematician John Allen Paulos (Paulos 2008, Irreligion. New York: Hill & Wang).
      This twenty-first century crusade against belief in God is best understood as a
      psychodynamic ignited by Altizer's Christian atheism. The present dialogue
      reflects that dynamic while the prologue and epilogue reveal evidence of
      Providence amidst claims of God's demise in contemporary history.

PMID- 19399625
TI  - An automated micro-solid phase extraction device involving integrated ?high
      pressure microvalves for genetic sample preparation.
AB  - This paper presents an automated micro-SPE device for DNA extraction using
      monolithically integrated high-pressure microvalves. The automated micro-SPE
      device was fabricated through glass-to-glass thermal bonding and microfluidic
      system interface technologies. To increase the DNA extraction efficiency, silica
      beads were packed in the extraction microchannel involving two weir structures.
      Experimental results show that the DNA extraction efficiency using the automated
      micro-SPE device containing bare silica beads was 75.87% in the first 8 microl of
      solution eluted by automated SPE procedure. In addition, the reproducibility of
      the DNA extraction was evaluated by ten successive measurements. Genomic DNA
      extracted from human WBCs had an absorbance ratio of DNA to protein
      (A(260)/A(280)) of 1.56. The applicability of this automated micro-SPE device to
      genetic sample preparation was verified by PCR amplification of a beta-globulin
      gene using the genomic DNA extracted from WBCs. Consequently, we demonstrated
      that the proposed automatic micro-SPE device can extract nucleic acids from
      biological samples, thereby facilitating its integration with downstream genetic
      analyses in a micro format.

PMID- 19399627
TI  - Optimization of hydrogels for transdermal delivery of lisinopril by Box-Behnken
      statistical design.
AB  - The aim of this study was to investigate the combined influence of three
      independent variables on the permeation kinetics of lisinopril from hydrogels for
      transdermal delivery. A three-factor, three-level Box-Behnken design was used to
      optimize the independent variables, Carbopol 971 P (X(1)), menthol (X(2)), and
      propylene glycol (X(3)). Fifteen batches were prepared and evaluated for
      responses as dependent variables. The dependent variables selected were
      cumulative amount permeated across rat abdominal skin in 24 h (Q (24); Y(1)),
      flux (Y(2)), and lag time (Y(3)). Aloe juice has been first time investigated as
      vehicle for hydrogel preparation. The ex vivo permeation study was conducted
      using Franz diffusion cells. Mathematical equations and response surface plots
      were used to relate the dependent and independent variables. The regression
      equation generated for the cumulative permeation of LSP in 24 h (Q(24)) was Y(1)
      = 1,443.3-602.59X(1) + 93.24X(2) + 91.75X(3) - 18.95X(1)X(2) - 140.93X(1)X(3) -
      4.43X(2)X(3) - 152.63X(1)(2) - 150.03X(2)(2) - 213.9X(3)(2). The statistical
      validity of the polynomials was established, and optimized formulation factors
      were selected by feasibility and grid search. Validation of the optimization
      study with 15 confirmatory runs indicated high degree of prognostic ability of
      response surface methodology. The use of Box-Behnken design approach helped in
      identifying the critical formulation parameters in the transdermal delivery of
      lisinopril from hydrogels.

PMID- 19399626
TI  - Metabolomics: moving to the clinic.
AB  - Assessment of a biological system by means of global and non-targeted metabolite
      profiling--metabolomics or metabonomics--provides the investigator with molecular
      information that is close to the phenotype in question in the sense that
      metabolites are an ultimate product of gene, mRNA, and protein activity. Over the
      last few years, there has been a rapidly growing number of metabolomics
      applications aimed at finding biomarkers which could assist diagnosis, provide
      therapy guidance, and evaluate response to therapy for particular diseases. Also,
      within the fields of drug discovery, drug toxicology, and personalized
      pharmacology, metabolomics is emerging as a powerful tool. This review seeks to
      update the reader on analytical strategies, biomarker findings, and implications
      of metabolomics for the clinic. Particular attention is paid to recent biomarkers
      found related to neurological, cardiovascular, and cancer diseases. Moreover, the
      impact of metabolomics in the drug discovery and development process is examined.

PMID- 19399629
TI  - Duality of effect of La3+ on mitochondrial permeability transition pore depending
      on the concentration.
AB  - In order to explore the role of mitochondria in proliferation promotion and/or
      apoptosis induction of lanthanum, the mutual influences between La3+ and Ca2+ on
      mitochondrial permeability transition pore (PTP) opening were investigated with
      isolated mitochondria from rat liver. The experimental results revealed that La3+
      influence the state of mitochondria in a concentration-dependent biphasic manner.
      La3+ in nanomolar concentrations, acting as a Ca2+ analog, entered mitochondrial
      matrix via the RuR sensitive Ca2+ channel and elevated ROS level, leading to
      opening of PTP indicated by mitochondrial swelling, reduction of DeltaPsim and
      cytochrome c release. Inhibition of PTP with 10 MUM CsA attenuated the effects of
      La3+. However, micromolar concentrations La3+ acted mainly as a Ca2+ antagonist,
      inhibiting PTP opening induced by Ca2+. We postulated that this action of La3+ on
      mitochondria through interaction with Ca2+ might be involved in the proliferation
      promoting and apoptosis induction by La3?.

PMID- 19399628
TI  - Effects of drug transporters on volume of distribution.
AB  - Recently, drug transporters have emerged as significant modifiers of a patient's
      pharmacokinetics. In cases where the functioning of drug transporters is altered,
      such as by drug-drug interactions, by genetic polymorphisms, or as evidenced in
      knockout animals, the resulting change in volume of distribution can lead to a
      significant change in drug effect or likelihood of toxicity, as well as a change
      in half life independent of a change in clearance. Here, we review
      pharmacokinetic interactions at the transporter level that have been investigated
      in animals and humans and reported in literature, with a focus on the changes in
      distribution volume. We pay particular attention to the differing effects of
      changes in transporter function on the three measures of volume. Further, trends
      are discussed as they may be used to predict volume changes given the function of
      a transporter and the primary location of the interaction. Because the liver and
      kidneys express the greatest level and variety of transporters, we denote these
      organs as the primary location of transporter-based interactions. We conclude
      that the liver is a larger contributor to distribution volume than the kidneys,
      in consideration of both uptake and efflux transporters. Further, while altered
      distribution due to secondary interactions at tissues other than the liver and
      kidneys may have a pharmacodynamic effect, these interactions, at least at the
      blood-brain barrier, do not appear to significantly influence overall
      distribution volume. The analysis provides a framework for understanding
      potential pharmacokinetic interactions rooted in drug transporters as they modify
      drug distribution.

PMID- 19399631
TI  - The endothelial cell tube formation assay on basement membrane turns 20: state of
      the science and the art.
AB  - It has been more than 20 years since it was first demonstrated that endothelial
      cells will rapidly form capillary-like structures in vitro when plated on top of
      a reconstituted basement membrane extracellular matrix (BME, Matrigel, EHS
      matrix, etc.). Subsequently, this morphological differentiation has been
      demonstrated with a variety of endothelial cells; with endothelial progenitor
      cells; and with transformed/immortalized endothelial cells. The differentiation
      process involves several steps in blood vessel formation, including cell
      adhesion, migration, alignment, protease secretion, and tubule formation. Because
      the formation of vessel structures is rapid and quantifiable, endothelial cell
      differentiation on basement membrane has found numerous applications in assays.
      Such differentiation has been used (1) to study angiogenic and antiangiogenic
      factors, (2) to define mechanisms and pathways involved in angiogenesis, and (3)
      to define endothelial cell populations. Further, the endothelial cell
      differentiation assay has been successfully used to study processes ranging from
      wound repair and reproduction to development and tumor growth. The assay is easy
      to perform and is the most widely used in vitro angiogenesis assay.

PMID- 19399632
TI  - Recent landscape change at the ecoregion scale in Southern Quebec (Canada), 1993
      2001.
AB  - Landsat images covering the St. Lawrence Lowlands (30,000 km(2)) and Appalachians
      (33,000 km(2)) ecoregions of southern Quebec, Canada, have been classified for
      the years 1993 and 2001 to (1) quantify land use/land cover (LULC) changes and
      changes to agricultural landscapes and (2) relate LULC changes to changes of farm
      related descriptors of economic and farming activities. Over 25 LULC classes were
      identified on each classification which were merged into 5 LULC classes
      (anthropogenic, annual crop, perennial crop, forest, water/wetlands) used to
      delineate a gradient of five types of agricultural landscapes. Transition
      matrices reveal a shift in major agricultural classes in the St. Lawrence
      Lowlands where perennial crops have been converted into annual crops.
      Furthermore, suburban sprawl was observed adjacent to major cities whereas
      overall forest cover was reduced. Changes in agricultural land classes were few
      in the agroforested landscapes of the Appalachian ecoregion. Landscapes dominated
      by intensive agriculture expanded onto adjacent regions previously under
      extensive agriculture. Most farm-related variables extracted from agriculture
      censuses showed an increase, reflecting an intensification of agriculture in both
      ecoregions though no clear association with LULC changes were revealed. Increase
      in annual crops may be related to intensive corn production associated with pig
      farming. Differences in landscape changes between the two ecoregions may be
      related to proximal causal factors such as soil topography and suitability for
      high-quality crops. Our analysis will provide baseline information to implement a
      monitoring program of habitat dynamics in this vast region.

PMID- 19399630
TI  - Physical activity in adolescence and testicular germ cell cancer risk.
AB  - OBJECTIVE: Several, but not all, studies have observed increased risks of
      testicular germ cell cancer (TGCC) associated with bicycling and other
      recreational activities. To further examine whether physical activity (PA) in
      adolescence is associated with TGCC risk, the authors conducted a case-control
      study in western Washington State. METHODS: Cases (n = 391) were men diagnosed
      with TGCC, who were identified through a population-based cancer registry.
      Controls (n = 1,023) were men identified from the general population in western
      Washington State by using random digit telephone dialing. Participants were
      queried about various specific PA in grades 7-12 including bicycling, horseback
      riding, competitive sports, physical education class, as well as moderate,
      vigorous, and sedentary activities in general. RESULTS: In multivariate analyses,
      bicycling, vigorous-intensity activities, and sedentary activities were not
      associated with TGCC risk, while horseback riding and wrestling were associated
      with decreased risks, and moderate-intensity activities, soccer, basketball, and
      intermediate duration of competitive activities were associated with increased
      risks. CONCLUSIONS: The lack of internal consistency of the findings within the
      current study and of findings among prior studies suggests that PA contributes
      little, if any, to the risk of TGCC.

PMID- 19399633
TI  - The changes of densities and patterns of roads and rural buildings: a case study
      on Dongzhi Yuan of the Loess Plateau, China.
AB  - Roads and buildings are considered as primary causes of rural landscape changes.
      In this study, linear regression models were used to analyze the dynamic
      influences of environmental factors and variables on roads and rural buildings
      from 1979 to 2005 in Dongzhi Yuan (tableland) of the Loess Plateau, China. The
      relationship between roads and rural buildings and their effects on Dongzhi Yuan
      are discussed also. The results showed that three environmental factors
      (topography, land cover, and development level) explained roads better than rural
      buildings referring densities and patterns. The environmental variables
      significantly related to roads have decreased, whereas those related to rural
      buildings have increased over time. Among these significant variables, percent of
      farmland mostly determined the densities and patterns of both roads and rural
      buildings. There was significant correlation between roads and rural buildings in
      terms of density and pattern. In addition, roads and rural buildings have
      increased greatly in gully areas of this region. Therefore, more attention should
      be paid to planning of roads and rural buildings in Dongzhi Yuan.

PMID- 19399634
TI  - Biological community structure on patch reefs in Biscayne National Park, FL, USA.
AB  - Coral reef ecosystem management benefits from continual quantitative assessment
      of the resources being managed, plus assessment of factors that affect
      distribution patterns of organisms in the ecosystem. In this study, we
      investigate the relationships among physical, benthic, and fish variables in an
      effort to help explain the distribution patterns of organisms on patch reefs
      within Biscayne National Park, FL, USA. We visited a total of 196 randomly
      selected sampling stations on 12 shallow (<10 m) patch reefs and measured
      physical variables (e.g., substratum rugosity, substratum type) and benthic and
      fish community variables. We also incorporated data on substratum rugosity
      collected remotely via airborne laser surveying (Experimental Advanced Airborne
      Research Lidar-EAARL). Across all stations, only weak relationships were found
      between physical, benthic cover, and fish assemblage variables. Much of the
      variance was attributable to a "reef effect," meaning that community structure
      and organism abundances were more variable at stations among reefs than within
      reefs. However, when the reef effect was accounted for and removed statistically,
      patterns were detected. Within reefs, juvenile scarids were most abundant at
      stations with high coverage of the fleshy macroalgae Dictyota spp., and the
      calcified alga Halimeda tuna was most abundant at stations with low EAARL
      rugosity. Explanations for the overwhelming importance of "reef" in explaining
      variance in our dataset could include the stochastic arrangement of organisms on
      patch reefs related to variable larval recruitment in space and time and/or
      strong historical effects due to patchy disturbances (e.g., hurricanes, fishing),
      as well as legacy effects of prior residents ("priority" effects).

PMID- 19399635
TI  - Coastline change assessment on water reservoirs located in the Konya Basin Area,
      Turkey, using multitemporal landsat imagery.
AB  - This paper focuses mainly on the coastline change assessment on water reservoirs
      located in the Konya Basin Area, Turkey. The Konya Closed Basin exists at the
      Central Anatolia Region and covers a region of 50,000 km(2) area corresponding to
      the 7% cumulative area of Turkey in which three million people live, 45% in rural
      areas and 55% in urban areas. The basin is surrounded with the city centers of
      Konya, Aksaray, Karaman, Isparta, Nigde, Ankara, Nevsehir, and Antalya cities. In
      this study, these changes were examined using Landsat TM and ETM+ 1987-2006 and
      1990-2000. In the image processing step, image and vectorization of the satellite
      images were carried out to monitor coastline changes over the lakes located in
      the Konya Closed Basin Area. At the end of the study, significant coastline
      movements were detected for a 19-year period due to drought effects, agricultural
      watering, and planning mistakes experienced in the basin.

PMID- 19399636
TI  - Attending to audience: comparing optometry student talk with and about patients.
AB  - We explored mediating concepts that affect clinical novices shifting between
      their talk with patients in eye examinations and their talk about patients in
      case presentations (nCPs). In a Canadian optometry teaching clinic, patient
      'chief concern or request', 'illness experience', and 'management' utterances
      were observed in ten eye examinations and nCPs. Twenty-three participants (8
      students, 5 instructors, and 10 patients) were observed; 22 were subsequently
      interviewed. Of 10 nCPs, the 'chief concern or request' was absent in four, the
      'illness experience' was incomplete or absent in 9 and 5 of 19 (35.7%)
      'management' topics were not discussed with patients. During eye exams, 17 of 31
      (54.8%) 'management' discussions with patients were not discussed with
      instructors during nCPs. Instructional 'scaffolding' (Bruner and Sherwood in
      Play: its role in development and evolution, p. 280, 1976) appeared limited
      regarding talk with and about patients. The limited and recontextualized
      reporting of patient concerns and experiences in nCPs represented lost
      opportunities to provide and learn patient-centered care. While Goffman's (The
      presentation of the self in everyday life, p. 114, 1969) 'front stage'
      performances and Mishler's (The discourse of medicine: dialectics of medical
      interviews, p. 14, 1984) healthcare 'voices' suggest separate worlds of talk
      before patients and instructors, we found these worlds were not wholly separate
      for neophyte speakers. Mediating concepts that influence clinical novices
      shifting their performances before their audiences, included: (1) pedagogical
      inconsistencies, (2) incompatible values associated with talk, (3) discordance
      between patient care and student education, (4) time limitations for teaching,
      and (5) insufficient instructional 'scaffolding' about talk.

PMID- 19399637
TI  - Salmonella Umbadah: a new Salmonella serovar isolated from cattle in Sudan.

PMID- 19399638
TI  - Management and outcome in 75 individuals with long-chain fatty acid oxidation
      defects: results from a workshop.
AB  - At present, long-chain fatty acid oxidation (FAO) defects are diagnosed in a
      number of countries by newborn screening using tandem mass spectrometry. In the
      majority of cases, affected newborns are asymptomatic at time of diagnosis and
      acute clinical presentations can be avoided by early preventive measures. Because
      evidence-based studies on management of long-chain FAO defects are lacking, we
      carried out a retrospective analysis of 75 patients from 18 metabolic centres in
      Germany, Switzerland, Austria and the Netherlands with special regard to
      treatment and disease outcome. Dietary treatment is effective in many patients
      and can prevent acute metabolic derangements and prevent or reverse severe long
      term complications such as cardiomyopathy. However, 38% of patients with very
      long-chain acyl-CoA dehydrogenase (VLCAD) deficiency had intermittent muscle
      weakness and pain despite adhering to therapy. Seventy-six per cent of patients
      with disorders of the mitochondrial trifunctional protein (TFP)-complex including
      long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, had long-term
      myopathic symptoms. Of these, 21% had irreversible peripheral neuropathy and 43%
      had retinopathy. The main principle of treatment was a fat-reduced and fat
      modified diet. Fat restriction differed among patients with different enzyme
      defects and was strictest in disorders of the TFP-complex. Patients with a medium
      chain fat-based diet received supplementation of essential long-chain fatty
      acids. l-Carnitine was supplemented in about half of the patients, but in none of
      the patients with VLCAD deficiency identified by newborn screening. In summary,
      in this cohort the treatment regimen was adapted to the severity of the
      underlying enzyme defect and thus differed among the group of long-chain FAO
      defects.

PMID- 19399639
TI  - CHEK2*1100delC does not contribute to risk to breast cancer among Malay, Chinese
      and Indians in Malaysia.
AB  - A truncating mutation (1100delC) in the cell cycle checkpoint kinase-2 gene,
      CHEK2, has been identified as a risk factor for familial and sporadic breast
      cancer in some Northern and Western European populations. However, the prevalence
      of CHEK2*1100delC in breast cancer appears to be population dependent. We
      analysed the prevalence of CHEK2*1100delC in 668 breast cancer cases, of which
      542 were invasive breast cancers, from a hospital-based cohort of breast cancer
      patients from Kuala Lumpur, Malaysia. The variant was not found in any patients
      in this cohort, suggesting that CHEK2*1100delC is rare in our population, and
      unlikely to contribute significantly to risk to breast cancer among the Malay,
      Chinese and Indian ethnic groups in Malaysia. This suggests that screening for
      this allele should not be routinely conducted in Malaysia.

PMID- 19399640
TI  - P2X(7) receptor expression is decreased in epithelial cancer cells of ectodermal,
      uro-genital sinus, and distal paramesonephric duct origin.
AB  - The P2X(7) receptor is an important regulator of epithelial cell growth. The aim
      of the present study was to better understand the biological significance of
      P2X(7) receptor expression in normal and cancer human epithelial tissues. P2X(7)
      receptor and messenger RNA (mRNA) levels were determined in human tissues
      containing epithelial dysplastic, pre- or early cancerous, and cancer cells, and
      the levels were compared to those in the corresponding normal epithelial cells
      within the same tissue of the same case. P2X(7) receptor levels were determined
      by quantification of immunoreactivity specific to the functional (full-length)
      P2X(7) receptor, and P2X(7) mRNA levels were determined by real-time polymerase
      chain reaction. P2X(7) receptor levels in cancer cells were similar (colon
      adenocarcinoma) or greater (thyroid papillary carcinoma) than those in the
      corresponding normal cells. In contrast, in cancer cells of the ectocervix
      (squamous), endocervix and endometrium (adenocarcinoma), urinary bladder
      (transitional cell carcinoma), and breast (ductal and lobular adenocarcinomas),
      P2X(7) receptor levels were lower by about twofold than those in the
      corresponding normal epithelial cells. Similarly, P2X(7) mRNA levels were lower
      in uterine, bladder, and breast cancer epithelial tissues by about fourfold than
      those in the corresponding normal tissues. In addition, P2X(7) receptor levels
      were decreased already in dysplastic ectocervical cells and pre- or early
      cancerous endometrial and bladder cells. The data suggest that in epithelia
      originating from the ectoderm, the uro-genital sinus, and the distal
      paramesonephric duct, decreased expression of the P2X(7) receptor precedes or
      coincides with neoplastic changes in those tissues.

PMID- 19399641
TI  - Rich can get poor: conversion of hub to non-hub proteins.
AB  - Hubs are ubiquitous network elements with high connectivity. One of the common
      observations about hub proteins is their preferential attachment leading to scale
      free network topology. Here we examine the question: does rich protein always get
      richer, or can it get poor too? To answer this question, we compared similar and
      well-annotated hub proteins in six organisms, from prokaryotes to eukaryotes. Our
      findings indicate that hub proteins retain, gain or lose connectivity based on
      the context. Furthermore, the loss or gain of connectivity appears to correlate
      with the functional role of the protein in a given system.

PMID- 19399642
TI  - Science and socially responsible freedom: commentary on "Cognitive enhancement:
      methods, ethics, regulatory challenges".

PMID- 19399643
TI  - Alternative splicing of CCN mRNAs .... it has been upon us.
AB  - Variant CCN proteins have been identified over the past decade in several normal
      and pathological situations. The production of CCN truncated proteins have been
      reported in the case of CCN2(ctgf), CCN3(nov), CCN4(wisp-1) and CCN6(wisp-3).
      Furthermore, the natural CCN5 is known to miss the C-terminal domain that is
      present in all other members of the CCN family of proteins. In spite of
      compelling evidence that assign important biological activities to these
      truncated CCN variants, their potential regulatory functions have only recently
      begun to be widely accepted. The report of CCN1(cyr61) intron 3 retention in
      breast cancer cells now confirms that, in addition to well documented post
      translational processing of full length CCN proteins, alternative splicing is to
      be regarded as another effective way to generate CCN variants. These observations
      add to a previous bulk of evidence that support the existence of alternative
      splicing for other CCN genes. It has become clearly evident that we need to
      recognize these mechanisms as a means to increase the biological diversity of CCN
      proteins.

PMID- 19399644
TI  - The cardiac effects of prolonged vitamin B12 and folate deficiency in rats.
AB  - In the recent past, hyperhomocysteinemia (HHCY) has been linked to chronic heart
      failure. Folate and vitamin B12 deficiencies are the common causes of HHCY. The
      impact of these vitamins on cardiac function and morphology has scarcely been
      investigated. The aim of this study was to conduct an analysis of the cardiac
      effect of folate and vitamin B12 deficiency in vivo. Two groups of rats, a
      control (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10), were fed for
      12 weeks with a folate and vitamin B12-free diet or an equicaloric control diet.
      Plasma and tissue concentrations of HCY, S-adenosyl-homocysteine (SAH), S
      adenosyl-methionine (SAM), and brain natriuretic peptide (BNP) were measured.
      Moreover, echocardiographic and histomorphometric analyses were performed. VitDef
      animals developed a significant HHCY (Co vs VitDef: 6.8 +/- 2.7 vs 61.1 +/- 12.8
      micromol/l, P < 0.001). Fractional shortening, left ventricular dimension at end
      diastole and end-systole, posterior wall thickness, perivascular collagen, mast
      cell number, and BNP tissue levels were comparable in VitDef and Co animals.
      Interstitial collagen (Co vs VitDef: 6.8 +/- 3.0 vs 4.5 +/- 2.1%, P < 0.05),
      plasma BNP (Co vs VitDef: 180 +/- 80 vs 70 +/- 60 ng/l, P < 0.05), and tissue HCY
      (Co vs VitDef: 0.13 +/- 0.07 vs 0.07 +/- 0.04 micromol/g protein, P < 0.05) were
      lower in VitDef animals. Folate and vitamin B12 deficiency do not affect cardiac
      function and morphology.

PMID- 19399645
TI  - The surgical treatment and outcome for primary duodenal adenocarcinoma.
AB  - BACKGROUND: Primary duodenal adenocarcinomas (PDAC) are uncommon tumors
      characterized by non-specific symptoms and late diagnosis, and treatments of PDAC
      have some controversies. METHOD: To investigate the early diagnosis and outcomes
      of surgical treatment of PDAC, 32 patients who were treated surgically between
      February 1990 and September 2006 were analyzed retrospectively. RESULTS: All 32
      patients underwent laparotomy, including 18 patients (56.3%) with
      pancreaticoduodenectomy (PD), six patients (18.7%) with segmental resection (SR),
      and eight patients with bypass procedures. And, R0 resections were obtained in 22
      patients; the other ten procedures were palliative. The total 1-, 3-, and 5-year
      survival rates in this study were 86.2% (25 of 29), 48.3% (14 of 29), and 20.7%
      (six of 29), respectively. Moreover, the 1-, 3-, and 5-year survival rates in
      patients with R0 resection were 100.0% (19 of 19), 73.7% (14 of 19), and 31.6%
      (six of 19), which were significantly higher than those (50.0% = 5/10, 0% and 0%)
      in patients with palliative operation (P < 0.05), respectively. Furthermore, the
      5-year survival rate was 27.8% (five of 18) in pancreaticoduodenectomy patients
      and 16.7% (one of six) in segmental resection patients, and there was no
      significant difference between the above two procedures (P > 0.05). CONCLUSION:
      PD is suggested for the tumor located at the first and second portion of the
      duodenum, and SR may be appropriate for the selected patients, especially for
      tumors of the distal duodenum.

PMID- 19399648
TI  - Possible role for ENPP1 polymorphism in obesity but not for INSIG2 and PLIN
      variants.
AB  - Previous studies have suggested that ENPP1, INSIG2, and PLIN may be linked with a
      higher risk for obesity or with increased phenotypic measures of obesity. We
      selected polymorphisms in these candidate genes based on their prior associations
      with obesity risk or obesity parameters. K121Q (rs1044498) in ENPP1, rs7566605 in
      INSIG2, and rs894160 in PLIN were genotyped by Taqman assays in a Belgian sample
      of 1,078 obese subjects (body mass index (BMI) > 30 kg/m(2)) and 323 lean
      controls (18.5 < BMI < 25 kg/m(2)). BMI, waist circumference, and waist-to-hip
      ratio (WHR) were assessed by standard methods while a computerized tomography
      scan was used to measure visceral (VFA), subcutaneous (SFA), and total (TFA)
      abdominal fat areas. Presence of the rare allele was not significantly different
      between cases and controls for the three variants that were tested, while only
      WHR was associated with ENPP1 in obese subjects. Our data thus indicate that
      K121Q, rs7566605, and rs894160 are not major contributing factors for obesity.

PMID- 19399647
TI  - GnRH receptor expression in human prostate cancer cells is affected by hormones
      and growth factors.
AB  - GnRH receptors (GnRH-R) have been found in various malignancies, including
      prostate cancer (PCa). They mediate the direct antitumor effects of GnRH analogs.
      Nevertheless, few reports concern drug-induced modulation of GnRH-R levels. In
      this study, we investigated GnRH-R expression in androgen-sensitive (LNCaP) and 
      insensitive (PC-3) PCa cells treated for 4 and 6 days with a GnRH agonist
      (Leuprorelin acetate, LA, 10(-11) or 10(-6) M), Dihydrotestosterone (DHT, 10(-9)
      M), Cyproterone acetate (CA, 10(-7) M), and Epidermal growth factor (EGF, 10
      ng/ml), either alone or combined. The RT-PCR analysis showed no variation in GnRH
      R mRNA levels of both treated LNCaP and PC-3 cells. On the contrary,
      immunoblotting indicated that in LNCaP and PC-3 cells, LA upregulated membrane
      GnRH-R expression (up to 92%). In androgen-sensitive cells, DHT induced a GnRH-R
      increase (up to 119%) always comparable to that occurring in the presence of CA.
      GnRH-R upregulation by LA/DHT or CA/DHT association was similar to that promoted
      by the single agents. In PC-3 cells, EGF upregulated GnRH-R (up to 110%). A
      prolonged treatment (for 12 days) determined a greater EGF-induced increase in
      GnRH-R levels (142%). Lower (or no) receptor enhancement occurred when LA and EGF
      were associated. Our findings indicate that LA post-transcriptionally upregulates
      its own membrane receptor in androgen-sensitive and -insensitive PCa cells,
      counteracting the receptor enhancement produced by DHT and EGF. The effects,
      obtained with a relatively long and continuous treatment, may have implications
      in the choice of therapy modality with GnRH analogs and may render the receptor a
      novel therapeutic target, particularly in hormone-refractory PCa.

PMID- 19399650
TI  - Mutations and polymorphisms in the SDHB, SDHD, VHL, and RET genes in sporadic and
      familial pheochromocytomas.
AB  - The prevalence of germ line mutations within the RET-protooncogene and the tumor
      suppressor genes SDHB, SDHD, and VHL in pheochromocytomas (PC) varies in recent
      studies from 12 to 24%, if one look at them collectively. DNA was extracted from
      frozen tumor tissue as well as from blood leukocytes of 36 PC (26 sporadic/10
      MEN2). Exons 1-8 of the SDHB-gene, 1-4 of the SDHD-gene, 1-3 of the VHL-gene, and
      exons 10, 11, 13, 14, 16 of the RET-gene were amplified by PCR and analyzed by
      DHPLC with the Transgenomic WAVE-System. Samples with aberrant wave profiles were
      subjected to direct sequencing. Genetic aberrations were correlated to clinical
      characteristics. Germ line mutations in sporadic PC were identified in four
      patients (11%) whereas somatic mutations were observed in two (5%) patients. Nine
      coding polymorphisms (PM) were identified in seven (19%) patients. Intronic
      variants were observed in six (17%) patients and were all located in the SHDB
      gene. Patients with wild type alleles in all assessed genes were older (53 vs. 37
      years, P = 0.007) and presented with an increased tumor size (49 vs. 32 mm, P =
      0.003) compared to patients with mutations. Malignant PC revealed multiple (>2)
      genetic alterations more frequently than benign PC (4/7 vs. 4/29, P = 0.03).
      Interestingly intronic variants of the SDHB gene occur more frequently in
      malignant than in benign PC (3/7 vs. 2/29, P = 0.04). The frequency of germ line
      mutations in sporadic pheochromocytomas was lower in our cohort than previously
      reported. Polymorphisms of the RET gene are common (17%) and occur in familial
      and sporadic PC. Multiple genetic alterations including mutations, polymorphisms
      and intronic variants are more frequently observed in malignant PC.

PMID- 19399649
TI  - A reverse postural test as a screening tool for aldosterone-producing adenoma: a
      pilot study.
AB  - The aldosterone-to-renin ratio (ARR) is an accepted screening tool for primary
      hyperaldosteronism (PA). An ambulatory case finding test to separate surgically
      remediable aldosterone-producing adenoma (APA) from other forms of PA, however,
      is currently not available. The aim of this study was to evaluate a reverse
      postural test (RPT) as a novel tool for identifying APA. We investigated 6
      healthy controls, 19 primary hypertensive patients, and a prospective cohort of
      32 patients clinically suspicious for primary hyperaldosteronism. We diagnosed
      seven patients with surgically proven APA, and three patients with idiopathic
      hyperaldosteronism. Serum aldosterone was measured after 30-min of moderate
      exercise (Aldo-1) and after a subsequent 2-h supine resting period (Aldo-2) with
      calculation of the ratio Aldo-2/Aldo-1. Aldosterone significantly decreased after
      supine resting in both healthy controls and primary hypertensives, but not in
      patients with APA. Receiver-operating-curve analysis revealed that the RPT was
      suitable for the screening of APA. A combination of the ratio Aldo-2/Aldo-1 >0.59
      and Aldo-2 >160 pg/ml correctly identified all the patients with APA, with no
      false positives. Although the high sensitivity of the RPT here observed needs to
      be confirmed in larger studies, the high positive predictive value of RPT could
      be useful for the identification of APA in outpatients.

PMID- 19399651
TI  - Feasibility of sequential use of sunitinib and temsirolimus in advanced renal
      cell carcinoma.
AB  - Targeted agents sunitinib and temsirolimus are effective in advanced renal cell
      carcinoma. Treatment algorithms for single-agent use have been proposed in order
      to optimize timing and type of therapy. The aim of this study was to investigate
      the tolerability and adverse event profile of patients who received sunitinib and
      temsirolimus in sequence. We performed a retrospective analysis of patients with
      advanced renal cell carcinoma who received temsirolimus after disease progression
      under sunitinib therapy. Dosages of both drugs were in accordance with the
      recommendations given by the respective manufacturers. Temsirolimus was provided
      before its official approval within a compassionate use program. Adverse event
      assessment followed the National Cancer Institute Common Toxicity Criteria.
      Thirteen patients receiving temsirolimus after progression under sunitinib were
      identified. Overall treatment time with targeted drugs (sunitinib/temsirolimus)
      was 34.8 (17-78) weeks, treatment with sunitinib was 28.6 (12-72), and with
      temsirolimus 6.2 (2-16) weeks, respectively, whereas mean therapy interruption
      time between both approaches was 4.4 (2-12) weeks. Under sunitinib, we observed
      52 transient adverse events, 49 (94.2%) were of grade I/II, whereas 3 (5.8%) were
      of grade III. Under temsirolimus 36 adverse events, only grade I/II in nature
      were remarked. Sequential use of temsirolimus after progression under sunitinib
      seems to be feasible and results in a predictable, medically manageable side
      effect profile. Further evaluation is necessary to define the oncological
      validity of this sequencing approach.

PMID- 19399652
TI  - GP73, a resident Golgi glycoprotein, is sensibility and specificity for
      hepatocellular carcinoma of diagnosis in a hepatitis B-endemic Asian population.
AB  - Golgi protein-73 (GP73) is a newly identified candidate serum marker for HCC, but
      GP73 study now is lesser in Asian population. The aims of this study were to
      determine how GP73 is detected in the serum of healthy, hepatitis B, cirrhosis
      and HCC by western blotting and RT-PCR, and to establish the sensitivity and
      specificity of serum GP73 protein and RNA for diagnosing HCC. Serum GP73 was
      detected by western blotting and RT-PCR, and quantified by densitometric
      analysis. GP73 was measured in serum from 124 patients with various forms of
      liver. AFP was tested using commercially available electrochemiluminescence
      immunoassay. The median sGP73 in patients with HBV-related HCC was significantly
      higher (P < 0.001) than in healthy individuals and in patients with other
      diseases. When sGP73 protein was used to detect HBV-related HCC, it had a
      sensitivity of 77.4% and a specificity of 83.9%, at the optimal cut-off value of
      7.4 relative units. The area under the receiver-operating characteristic curve
      was 0.89. GP73 RNA in patients with HBV-related HCC had a sensitivity of 87.1%
      and a specificity of 83.9% and AUROC of 0.92. AFP in patients with HCC had a
      sensitivity of 48.4% and a specificity of 96.8% and AUROC of 0.77. GP73 protein
      and RNA can be found in the serum of patients with HBV-related HCC obviously
      higher than of other liver diseases in Asian. GP73 was better than AFP for the
      diagnosis of HBV-related HCC. RT-PCR is a more sensitive and superior method of
      quantification than Western blot. Furthermore, our data need to be confirmed in
      larger cohorts of patients.

PMID- 19399654
TI  - Response to low level DNA profiling.

PMID- 19399653
TI  - Prognostic factors in patients with small cell lung carcinoma.
AB  - BACKGROUND: The current prognosis in patients with small cell lung cancer (SCLC)
      is unsatisfactory, even though there have been considerable improvements in
      diagnosis and treatment. METHODS: We retrospectively analyzed all consecutive
      patients with small cell lung carcinoma between 1995 and 2007 in a Turkish chest
      hospital. A total of 116 SCLC patients initially presented with limited disease,
      while 92 small cell lung carcinoma patients were found to be extensive. RESULTS:
      The mean age of the patients (18 women and 190 men) was 56 years. The median
      survival was 74 weeks. Performance status, superior vena cava syndrome (SVCS),
      stage, elevated white blood cell count, elevated lactate dehidrogenase levels,
      short symptom duration (<or=4 weeks) response to chemotherapy and bone metastasis
      were significant prognostic factors in univariate analysis. It was necessary for
      patients to receive at least three cycles of chemotherapy for a survival benefit.
      Cox proportional hazards model identified only stage, performance status and SVCS
      as independent prognostic factors. CONCLUSIONS: Stage, performance status and
      SVCS were determined to be the most important prognostic factors for SCLC
      patients.

PMID- 19399657
TI  - Abstracts of the Royal Australian and New Zealand College of Psychiatrists 44th
      Congress. May 24-28, 2009. Adelaide, South Australia, Australia.

PMID- 19399659
TI  - Analysis of dialkyl phosphate metabolites in hair using gas chromatography-mass
      spectrometry: a biomarker of chronic exposure to organophosphate pesticides.
AB  - The aim of our study was to develop and validate an analytical approach for the
      quantitative determination of three dialkyl phosphate (DAP) metabolites, dimethyl
      phosphate (DMP), dimethyl thiophosphate (DMTP) and diethyl phosphate (DEP), of
      organophosphate pesticides (OPs) in hair samples. The proposed methodology
      comprises a decontamination step, solid-liquid extraction, followed by liquid
      liquid extraction, pentafluorobenzyl bromide derivatization, clean-up on
      Florisil/PSA column and analysis by gas chromatography-mass spectrometry (GC-MS).
      Extraction recovery, obtained from 50 mg hair samples spiked at two concentration
      levels, ranged from 56.1 to 107.9% and the within-day precision ranged from 13.5
      to 17.5%. Limits of detection (LODs) ranged from 0.02 to 0.10 ng mg(-1). The
      results obtained from the analysis of hair samples of 30 agricultural workers
      show the suitability of the proposed method for monitoring people occupationally
      exposed to OPs. The most frequently detected compound was DEP followed by DMP.
      This is the first report on the detection of dialkyl phosphates in human hair
      which reflects the ability of hair testing to assess chronic exposure to OPs.

PMID- 19399661
TI  - Multiplication of neutrophil and monocyte counts (MNM) as an easily obtainable
      tumour marker for cervical cancer.
AB  - Simple, non-aversive methods to identify cervical neoplasia are needed. The
      purpose of this study was to investigate the clinical value of differential white
      blood cell (WBC) counts as a biomarker for cervical neoplasia. We performed a
      retrospective review of laboratory results in 407 cervical cancers, 495 cervical
      intraepithelial neoplasias (CIN) and 916 healthy controls. Because pretreatment
      neutrophil and monocyte counts showed the potential as a biomarker, we combined
      these parameters and designated this combined marker MNM (multiplication of
      neutrophil and monocyte counts). MNM showed a sensitivity of 53.1% and a
      specificity of 78.1%, which are much higher than those of SCC-Ag. On Cox
      multivariate analysis, MNM positivity (hazard ratio = 2.82, p = 0.042), stage and
      tumour size were independent predictors of poor prognosis. Our findings suggest
      that pretreatment MNM could be a candidate as a simple and cost-effective
      biomarker in cervical cancer.

PMID- 19399660
TI  - Plasma levels of S100A4 in portopulmonary hypertension.
AB  - We previously showed that a single nucleotide polymorphism in S100A4 was
      associated with portopulmonary hypertension (PPHTN) in patients with advanced
      liver disease. We aimed to determine the association between plasma levels of
      S100A4 and PPHTN. We performed a case-control study of patients with advanced
      liver disease. Cases with PPHTN had mean pulmonary artery pressure >25 mmHg,
      pulmonary vascular resistance >240 dynes s cm(-5) and pulmonary capillary wedge
      pressure </=15 mmHg. Controls with liver disease had right ventricular systolic
      pressure <40 mmHg and normal right atrial and ventricular morphology by
      echocardiography. Plasma samples were assayed for S100A4. The study sample
      included 14 cases with PPHTN and 32 controls with liver disease. There was no
      difference in mean age between cases and controls (p = 0.52). Seventy-nine
      percent of cases were female compared with 44% of controls (p = 0.03). There was
      no difference in S100A4 levels between cases and controls (p = 0.58). Both groups
      had significantly higher S100A4 levels than healthy volunteers (p <0.05). There
      was no significant difference in plasma levels of S100A4 between PPHTN patients
      and controls with liver disease, although liver disease itself was associated
      with increased S100A4 levels.

PMID- 19399662
TI  - Biochemical markers and the FDA Critical Path: how biomarkers may contribute to
      the understanding of pathophysiology and provide unique and necessary tools for
      drug development.
AB  - The aim of this review is to discuss the potential usefulness of a novel class of
      biochemical markers, neoepitopes, in the context of the US Food and Drug
      Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of
      safety and efficacy as areas of pivotal interest. Examples of protein degradation
      fragments--neoepitopes--that have proven useful for research on bone and
      cartilage are collagen type I and collagen type II degradation products,
      respectively. These markers have utility in the translational approach, as they
      can be used to estimate safety and efficacy in both preclinical models and
      clinical settings. Biochemical markers of tissue degradation may provide optimal
      tools, which in combination with other techniques, prove essential to drug
      discovery and development.

PMID- 19399664
TI  - Effect of listener training on perceptual judgement of hypernasality.
AB  - Reliable perceptual judgement is important for documenting the severity of
      hypernasality, but high reliability can be difficult to obtain. This study
      investigated the effect of practice and feedback on intra-judge and inter-judge
      reliability of hypernasality judgements. The judges were 36 speech-language
      therapy students, who were randomly assigned to three groups for training: (1)
      Exposure (simple exposure to hypernasal speech samples), (2) Practice-only
      (practice with hypernasality judgements without feedback), and (3) Practice
      Feedback (practice with hypernasality judgements with feedback). After training,
      the judges rated hypernasality in non-nasal sentences produced by 20 speakers
      with hypernasality and two normal speakers, using direct magnitude estimation.
      Both practice groups showed fair-to-good inter-judge reliability for rating the
      female samples: had more listeners who showed significant intra-judge
      reliability, and had significantly larger range of hypernasality ratings than the
      exposure group. To conclude, practice (with or without feedback) is useful for
      improving the reliability of hypernasality ratings.

PMID- 19399665
TI  - Hesitation patterns in third grade children's derived word productions.
AB  - Hesitations have been considered to serve both cognitive and linguistic
      functions. This study presents analyses of children's hesitations while producing
      English derived words with the suffix -ity. Two questions were considered: Do
      children's linguistic skills influence their use and frequency of hesitations
      when producing derived words, and do children's use of hesitations vary as a
      function of word frequency. Eight real words derived with the suffix -ity were
      produced by 20 third grade children and analysed for different hesitation types.
      Four of the target words were high in lexical frequency, and four were low in
      lexical frequency. Results indicated varying hesitation patterns based upon
      stress accuracy skill. Children with good stress accuracy skills tended to
      produce false starts, whereas children with poor stress accuracy skills tended to
      produce glottal stops and intra-word pauses. Word frequency had a specific effect
      only for children with good stress accuracy skills.

PMID- 19399666
TI  - Acoustic analysis of voice in dysarthria following stroke.
AB  - Although perceptual studies indicate the likelihood of voice disorders in persons
      with stroke, there have been few objective instrumental studies of voice
      dysfunction in dysarthria following stroke. This study reports automatic analysis
      of sustained vowel phonation for 61 speakers with stroke. The results show: (1)
      men with stroke and healthy elderly men exhibited an identical voice profile, and
      men with stroke had only one significantly larger noise parameter (SPI--soft
      phonation index) than young healthy men; and (2) women with stroke and healthy
      elderly women exhibited an identical voice profile, except that women with stroke
      exhibited a significantly higher SPI than healthy elderly women. Although there
      were no significant differences in smoothed pitch perturbation quotient (sPPQ)
      and SPI between healthy elderly women and healthy young women, women with stroke
      exhibited significantly larger sPPQ and SPI than healthy young women. It is
      suggested that studies on sub-groups of the stroke population that use a
      combination of perceptual and acoustic analyses will better illuminate the voice
      dysfunction in dysarthria following stroke.

PMID- 19399667
TI  - Comprehension and production of noun compounds by Estonian children with specific
      language impairment.
AB  - The authors examined how 12 Estonian-speaking children with specific language
      impairment (SLI) and 60 children with normal speech development (ND) comprehended
      compound nouns with differing sequence of the components (first task) and how
      they produced compound nouns to label genuine and accidental categories by using
      analogy (second task) and sentence transformation (third task). The results
      demonstrated that children with SLI were capable of producing compound nouns for
      genuine categories, but avoided production of compounds to label objects in
      temporary juxtapositions. However, by comparison with the control group, SLI
      children differed statistically significantly in terms of both the number of
      correct answers and the pattern of mistakes. In the cases when compound nouns
      were expected to be produced by transforming sentences, the results of SLI
      children were considerably lower than those of their peers. The results of this
      study support the idea that children with SLI experience difficulties related to
      processing linguistic information.

PMID- 19399668
TI  - A thought on the biological activities of black tea.
AB  - Tea is the most widely used ancient beverage in the world and black tea possesses
      many biological effects on the organisms. It acts as an effective antioxidant
      because of its free radical-scavenging and metal-chelating ability. Due to this,
      it is active against inflammation, clastogenesis, and several types of cancer.
      Tea reduces DNA damage and mutagenesis due to oxidative stress or the presence of
      pro-mutagens through antioxidant function, blocking activation pathways of
      mutagens, suppressing transcription of enzymes involved etc. Inhibition of low
      density lipoprotein (LDL) peroxidation, suppression of fatty acid synthase etc.,
      suggest that tea may have a role in preventing cardiovascular diseases. Some
      epidemiological studies support the protective role of black tea against
      cardiovascular diseases but some do not. Besides, black tea has beneficial
      effects on the gastrointestinal tract; it affects motility, absorption,
      microflora etc., by influencing the hormonal balance and antioxidant function
      black tea improves bone mineral density. It is also antiviral due to its enzyme
      inhibiting and receptor-blocking properties. Although its role in cancers of the
      gastrointestinal tract, liver, and prostate is confirmed, its effect against
      urinary tract cancer is uncertain and further studies are required. Apart from
      these, excess consumption may lead to the formation of a stained pellicle layer
      on teeth, which is difficult to eliminate, inhibits trypsin, influences mineral
      absorption, causes convulsions etc. Excess caffeine intake may have adverse
      effects on selected organs as reported in studies on some organisms. These
      reports indicate that there is a wide scope of further research for the efficient
      use of black tea active conserves/isolates to reap health benefits.

PMID- 19399669
TI  - Shelf life of packaged bakery goods--a review.
AB  - Packaging requirements for fresh bakery goods are often minimal as many of the
      products are for immediate consumption. However, packaging can be an important
      factor in extending the shelf life of other cereal-based goods (toast, frozen
      products, biscuits, cakes, pastas). Some amount of the texture changes and flavor
      loss manifest over the shelf life of a soft-baked good can usually be minimized
      or delayed by effective use of packaging materials. The gains in the extension of
      shelf life will be application specific. It is recognized that defining the shelf
      life of a food is a difficult task and is an area of intense research for food
      product development scientists (food technologists, microbiologists, packaging
      experts). Proper application of chemical kinetic principles to food quality loss
      allows for efficiently designing appropriate shelf-life tests and maximizing the
      useful information that can be obtained from the resulting data. In the
      development of any new food product including reformulating, change of packaging,
      or storage/distribution condition (to penetrate into a new market), one important
      aspect is the knowledge of shelf life.

PMID- 19399670
TI  - Irradiation applications in vegetables and fruits: a review.
AB  - There is an increasing trend both in advanced countries and many developing
      countries to centrally process fresh fruits and vegetables, properly packaged,
      for distribution and marketing. Irradiation technology proved to be effective in
      reducing post-harvest losses, and controlling the stored product insects and the
      microorganisms. Gamma irradiation was employed to restrain potato sprouting and
      kill pests in grain. Irradiation proved to be extremely beneficial in terms of
      prolonging the fruit and vegetable shelf life by 3-5 times. In order not to
      expose fruits and vegetables to high irradiation doses another approach is to use
      the "hurdle technology," that is to apply more than one technology toward better
      quality and longer shelf life. This review summarizes a) all the obtained results
      in this field (either irradiation on its own or in conjunction with other
      technologies) on fruits and vegetables in 11 figures and eight (8) very
      comprehensive tables, and b) provides an insight in the various methods (EPR, TL,
      Comet assay among others) for detection of irradiated foods.

PMID- 19399671
TI  - Green tea: nature's defense against malignancies.
AB  - The current practice of introducing phytochemicals to support the immune system
      or fight against diseases is based on centuries old traditions. Nutritional
      support is a recent advancement in the domain of diet-based therapies; green tea
      and its constituents are one of the important components of these strategies to
      prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic
      activities of green tea were highlighted some years ago suggesting that it could
      reduce the prevalence of cancer and even provide protection. The pharmacological
      actions of green tea are mainly attributed to polyphenols that includes
      epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate,
      epigallocatechin. Green tea and its components effectively mitigate cellular
      damage arising due to oxidative stress. Green tea is supposed to enhance humoral
      and cell-mediated immunity, decreasing the risk of certain cancers, and may have
      certain advantage in treating inflammatory disorders. Much of the cancer
      chemopreventive properties of green tea are mediated by EGCG that induces
      apoptosis and promotes cell growth arrest, by altering the expression of cell
      cycle regulatory proteins, activating killer caspases, and suppressing nuclear
      factor kappa-B activation. Besides, it regulates and promotes IL-23 dependent DNA
      repair and stimulates cytotoxic T cells activities in a tumor microenvironment.
      It also blocks carcinogenesis by modulating the signal transduction pathways
      involved in cell proliferation, transformation, inflammation and metastasis. The
      review is intended to highlight the chemistry of green tea, its antioxidant
      potential, its immunopotentiating properties and mode of action against various
      cancer cell lines that showed its potential as a chemopreventive agent against
      colon, skin, lung, prostate, and breast cancer.

PMID- 19399672
TI  - Edible moisture barriers: how to assess of their potential and limits in food
      products shelf-life extension?
AB  - Control of moisture transfer inside composite food products or between food and
      its environment remains today a major challenge in food preservation. A wide rage
      of film-forming compounds is now available and facilitates tailoring moisture
      barriers with optimized functional properties. Despite these huge potentials, a
      realistic assessment of the film or coating efficacy is still critical. Due to
      nonlinear water sorption isotherms, water-dependent diffusivities, and variations
      of physical state, modelling transport phenomena through edible barriers is
      complex. Water vapor permeability can hardly be considered as an inherent
      property of films and only gives a relative indication of the barrier efficacy.
      The formal or mechanistic models reported in literature that describe the
      influence of testing conditions on the barrier properties of edible films are
      reviewed and discussed. Most of these models have been validated on a narrow
      range of conditions. Conversely, few original predictive models based on Fick's
      Second Law have been developed to assess shelf-life extension of food products
      including barriers. These models, assuming complex and realistic hypothesis, have
      been validated in various model foods. The development of nondestructive methods
      of moisture content measurement should speed up model validation and allow a
      better comprehension of moisture transfer through edible films.

PMID- 19399673
TI  - Physico-chemical quality and homogeneity of folic acid and iron in enriched flour
      using principal component analysis.
AB  - The aim of the present work was to determine parameters of the corn and wheat
      flour matrix, such as protein, lipid, moisture, ash and carbohydrates, folic acid
      and iron contents. Three principal components explained 91% of the total
      variance. Wheat flours were characterized by high protein and moisture content.
      On the other hand, the corn flours had the greater carbohydrates, lipids and
      folic acid levels. The concentrations of folic acid were lower than the issued
      value for wheat flours. Nevertheless, corn flours presented extremely high
      values. The iron concentration was higher than that recommended in Brazilian
      legislation. Poor homogenization of folic acid and iron was observed in enriched
      flours. This study could be useful to help the governmental authorities in the
      enriched food programs evaluation.

PMID- 19399674
TI  - Obituary: Professor Gunnar Ahnstrom (1929-2008).

PMID- 19399675
TI  - Cellular effects of extremely low frequency (ELF) electromagnetic fields.
AB  - PURPOSE: The major areas of research that have characterised investigation of the
      impact of extremely low frequency (ELF) electromagnetic fields on living systems
      in the past 50 years are discussed. In particular, selected studies examining the
      role of these fields in cancer, their effects on immune and nerve cells, and the
      positive influence of these ELF fields on bone and nerve cells, wound healing and
      ischemia/reperfusion injury are explored. CONCLUSIONS: The literature indicates
      that there is still no general agreement on the exact biological detrimental
      effects of ELF fields, on the physical mechanisms that may be behind these
      effects or on the extent to which these effects may be harmful to humans.
      Nonetheless, the majority of the in vitro experimental results indicate that ELF
      fields induce numerous types of changes in cells. Whether or not the
      perturbations observed at the cellular level can be directly extrapolated to
      negative effects in humans is still unknown. However, the myriad of effects that
      ELF fields have on biological systems should not be ignored when evaluating risk
      to humans from these fields and, consequently, in passing appropriate legislation
      to safeguard both the general public and professionally-exposed workers. With
      regard to the positive effects of these fields, the possibility of testing
      further their efficacy in therapeutic protocols should also not be overlooked.

PMID- 19399676
TI  - Static electric fields interfere in the viability of cells exposed to ionising
      radiation.
AB  - PURPOSE: The interference of electric fields (EF) with biological processes is an
      issue of considerable interest. No studies have as yet been reported on the
      combined effect of EF plus ionising radiation. Here we report studies on this
      combined effect using the prokaryote Microcystis panniformis, the eukaryote
      Candida albicans and human cells. MATERIALS AND METHODS: Cultures of Microcystis
      panniformis (Cyanobacteria) in glass tubes were irradiated with doses in the
      interval 0.5-5 kGy, using a (60)Co gamma source facility. Samples irradiated with
      3 kGy were exposed for 2 h to a 20 V . cm(-1) static electric field and viable
      cells were enumerated. Cultures of Candida albicans were incubated at 36 degrees
      C for 20 h, gamma-irradiated with doses from 1-4 kGy, and submitted to an
      electric field of 180 V . cm(-1). Samples were examined under a fluorescence
      microscope and the number of unviable (red) and viable (apple green fluorescence)
      cells was determined. For crossing-check purposes, MRC5 strain of lung cells were
      irradiated with 2 Gy, exposed to an electric field of 1250 V/cm, incubated
      overnight with the anti-body anti-phospho-histone H2AX and examined under a
      fluorescence microscope to quantify nuclei with gamma-H2AX foci. RESULTS: In
      cells exposed to EF, death increased substantially compared to irradiation alone.
      In C. albicans we observed suppression of the DNA repair shoulder. The effect of
      EF in growth of M. panniformis was substantial; the number of surviving cells on
      day-2 after irradiation was 12 times greater than when an EF was applied. By the
      action of a static electric field on the irradiated MRC5 cells the number of
      nuclei with gamma-H2AX foci increased 40%, approximately. CONCLUSIONS:
      Application of an EF following irradiation greatly increases cell death. The
      observation that the DNA repair shoulder in the survival curve of C. albicans is
      suppressed when cells are exposed to irradiation + EF suggests that EF likely
      inactivate cellular recovering processes. The result for the number of nuclei
      with gamma-H2AX foci in MRC5 cells indicates that an EF interferes mostly in the
      DNA repair mechanisms. A molecular ad-hoc model is proposed.

PMID- 19399677
TI  - The influence of differently polarised microwave radiation on chromatin in human
      cells.
AB  - PURPOSE: To determine the possible biological effects of differently polarised
      microwave radiation on the chromatin state in human cells. MATERIALS AND METHODS:
      Isolated human buccal epithelium cells were irradiated by microwaves of frequency
      f = 35 GHz and surface power density E = 30 microW/cm(2). The state of chromatin
      in human cells was determined by methods of light and electron microscopy. The
      state of cell membranes was evaluated by the method of vital indigo carmine
      staining. RESULTS: The microwave-induced condensation of chromatin in human cells
      is revealed. Degree of microwave-induced condensation depends on the state of
      polarisation of electromagnetic wave: In some cases left circularly polarised
      waves induce less effect than linearly polarised radiation. The linearly
      polarised electromagnetic waves induce cell membrane damage revealed by increase
      of cell staining. The data obtained are discussed in connection with mechanisms
      of biological effects of electromagnetic fields. CONCLUSION: The data obtained in
      this work demonstrate important biological effects of monochromatic microwave
      irradiation at 35 GHz. Low-level microwave irradiation induces chromatin
      condensation in human cells and damages of cell membranes.

PMID- 19399678
TI  - High dose rate radiation treatment of experimental intramuscular prostate
      carcinoma.
AB  - PURPOSE: The Dunning R3327-MLL is a well established transplanted tumour line,
      and as such it makes a desirable model for evaluative studies of therapy. In the
      current study, the interstitial growth characteristics as well as the response of
      this tumour to a single fraction of high dose rate radiation is investigated.
      MATERIALS AND METHODS: The in vitro response to radiation of the Dunning R3327
      MLL was studied via a colony forming assay using a Cs-137 irradiator. In vitro
      radiosensitivity was determined on tumours implanted intramuscularly in the left
      gastrocnemius muscle of the rat and irradiated using an Ir-192 afterloader.
      RESULTS: The results demonstrate a faster growth rate when compared to the
      reported subcutaneous growth rates. The Dunning R3327-MLL's radiosensitivity is
      comparable to that of late response tissues. The dose required to achieve a
      specific radiobiological response (the alpha:beta ratio) of the in vitro cell
      line is 2.4 Gy, whereas the ratio for the intramuscularly growing tumour was 0.99
      Gy. CONCLUSIONS: These findings signify the intramuscularly implanted Dunning
      R3327-MLL tumour model as a desirable model for the study of single fraction high
      dose rate radiation treatments.

PMID- 19399679
TI  - Thorium-induced neurobehavioural and neurochemical alterations in Swiss mice.
AB  - PURPOSE: Thorium ((232)Th), a heavy metal radionuclide that targets the liver and
      skeleton, has been shown to accumulate in the central nervous system at low
      levels. The present study was aimed to investigate neurobehavioural and
      neurochemical changes in mice treated with (232)Th at sub-lethal doses. MATERIALS
      AND METHODS: Swiss albino mice were administered intraperitoneally with thorium
      nitrate. The chelation-based therapeutic effect of calcium diethylenetriamine
      pentaacetate (Ca-DTPA) was tested on the (232)Th-treated mice. (232)Th
      localisation was determined in brain regions by the Inductively Coupled Plasma
      Atomic Emission Spectroscopy (ICP-AES) method. Achetylcholine esterase (AChE)
      activity in different brain regions was evaluated to assess the cholinergic
      function of mice CNS. Oxidative damage was evaluated by assessing the activities
      of antioxidant enzymes (i.e., superoxide dismutase and catalase) and the level of
      lipid peroxidation. The neurobehavioural alteration in the treated mice was
      studied by the shuttle box method. RESULTS: (232)Th accumulation found in
      different brain regions followed the order: Cerebellum (Cbl) > cortex (Ctx) >
      hippocampus (Hp) > striatum (Str). However, removal of (232)Th by Ca-DTPA was
      significant from brain regions like Cbl, Ctx and Str but not from Hp. A
      significant increase in lipid peroxidation and acetylcholine esterase (AChE)
      activity was observed in the treated mice but activities of superoxide dismutase
      and catalase was found substantially decreased. (232)Th treatment impaired the
      learning and memory-based neurobehaviour of the mice. Furthermore, our data
      suggest that Ca-DTPA injection in (232)Th-treated animals failed to improve the
      neurobehaviour of the treated mice, perhaps because Ca-DTPA could not decorporate
      (232)Th or mitigate (232)Th-mediated neurochemical changes effectively from/in
      hippocampus, a brain region implicated in learning and memory response.
      CONCLUSION: Administration of (232)Th in mice caused neurobehavioural alteration
      and impairment of cholinergic function, which might be the consequence(s) of
      oxidative stress induction in different brain regions.

PMID- 19399680
TI  - Desferrithiocin analogue uranium decorporation agents.
AB  - PURPOSE: Previous systematic structure-activity studies of the desferrithiocin
      (DFT) platform have allowed the design and synthesis of analogues and derivatives
      of DFT that retain the exceptional iron-clearing activity of the parent, while
      eliminating its adverse effects. We hypothesized that a similar approach could be
      adopted to identify DFT-related analogues that could effectively decorporate
      uranium. MATERIALS AND METHODS: The decorporation properties of nine DFT-related
      analogues were determined in a bile duct-cannulated rat model.
      Diethylenetriaminepentaacetic acid (DTPA) served as a positive control. Selected
      ligands also underwent multiple and delayed dosing regimens. Uranium excretion in
      urine and bile or stool was determined by inductively coupled plasma mass
      spectroscopy (ICP-MS); tissue levels of uranium were also assessed. RESULTS: The
      two best clinical candidates are (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9
      trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE
      (9)], with a 57% reduction in kidney uranium levels on oral (p.o.) administration
      and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4
      thiazolecarboxylic acid [(S)-3'-(HO)-DADFT-PE (10)], with a 62% renal reduction
      on p.o. administration. The majority of the metal excretion promoted by these
      analogues is in the bile, thus further reducing kidney actinide exposure.
      CONCLUSIONS: While 9 administered p.o. or subcutaneously (s.c.) immediately post
      metal is an effective decorporation agent, withholding the dose (s.c.) until 4 h
      reduced the activity of the compound. Conversion of 9 to its isopropyl ester may
      circumvent this issue.

PMID- 19399681
TI  - Inactivation of bacteria by a mixed argon and oxygen micro-plasma as a function
      of exposure time.
AB  - PURPOSE: A radio-frequency dielectric barrier discharge (DBD) was applied as a
      micro-plasma device for the inactivation of bacteria, e.g., Escherichia coli.
      MATERIALS AND METHODS: The cultured bacteria were placed on a polydimethyl
      siloxane (PDMS) film and placed inside the DBD cavity. The bacteria were exposed
      to micro-plasmas of varying oxygen/argon ratios for different exposure times. The
      survival of the bacteria was measured by determining bacterial growth using
      optical methods. RESULTS: The excited oxygen species increased with the increase
      in the oxygen to argon ratio as measured by optical emission spectroscopy (OES),
      but the increase of excited oxygen species in argon micro-plasma did not enhance
      the inactivation of bacteria. In contrast, increases in the time the bacteria
      were exposed to the micro-plasma were of importance. The results show that a
      continuous plasma flow containing energetic and reactive species may result in
      electro-physical interactions with bacteria exposed to the plasma leading to
      their inactivation. CONCLUSION: For currently-employed DBD device, addition of
      0.5% oxygen to the argon micro-plasma for an exposure time of 30 sec was optimum
      for the inactivation of E. coli.

PMID- 19399682
TI  - The response of gamma-H2AX in human lymphocytes and lymphocytes subsets measured
      in whole blood cultures.
AB  - PURPOSE: To assess the use of phosphorylated histone H2AX protein (gamma-H2AX) in
      human blood leukocytes as a rapid screening tool for radiation biodosimetry using
      a method that examines the characteristics of gamma-H2AX phosphorylation in a
      variety of lymphocyte subsets following exposure to radiation. MATERIALS AND
      METHODS: Human peripheral blood exposed to 0-10 Gy of (137)Cs irradiation and
      cultured for 0-48 h was analysed using a rapid whole blood flow cytometry assay
      to measure gamma-H2AX phosphorylation in different lymphocyte subpopulations.
      RESULTS: Lymphocyte subsets displayed a similar linear dose response
      relationship, although cluster of differentiation 4(+) (CD4(+)) and CD8(+)
      lymphocytes were found to express H2AX phosphorylation on the order of 1.5 times
      higher than CD19(+) lymphocytes. Phosphorylation of all lymphocyte subsets
      reached a maximum at 1.5 h and had essentially returned to baseline levels 24 h
      post-exposure. CONCLUSIONS: Differences in the expression level of gamma-H2AX
      between lymphocyte subsets were minimal. The usefulness of this assay for
      radiation biodosimetry is hampered by its relatively quick lifetime kinetics and
      large inter-individual variation. Therefore, it could only be useful if samples
      were obtained within 24 h of exposure. Even in this situation, the assay could
      only be used as an indicator of exposure and not a dosimeter.

PMID- 19399683
TI  - Community health nursing student experience in Nicaragua.
AB  - International clinical experiences can provide excellent opportunities for
      nursing students to practice community health nursing, enhance their global
      perspective, and increase their cultural awareness of vulnerable populations.
      Selected students from the Georgetown University nursing program spent part of
      their winter intercession in Nicaragua, working with a vulnerable population in
      an impoverished community. Students cared for families, worked in clinics,
      conducted health teaching sessions to large groups in the community, and held a
      health fair. A community assessment provided an experience in learning about the
      resources and demographics of the community. The program was feasible through the
      collaboration with the local Nicaraguan university nursing program.

PMID- 19399684
TI  - Collaboration between nurses and professional caregivers to provide medical care
      in Japan.
AB  - In Japan, as more people require medical care, the importance of effective
      collaboration between nurses and professional caregivers, both in the home
      setting and in nursing home facilities, is increasing. The purpose of this study
      was to identify differences in the way professional caregivers in Japan view
      medical care administration in the home and in nursing home facilities. Responses
      to a questionnaire given to in-home and nursing home caregivers demonstrated that
      many professional caregivers, especially nursing home caregivers, desired
      collaboration with nurses to enable them to provide safe medical care. An
      educational system for professional caregivers in Japan is needed.

PMID- 19399685
TI  - The relationship between body mass index (weight status) and hypertension in a
      cohort of elementary school students: a retrospective longitudinal study.
AB  - This study longitudinally investigated the relationship between childhood body
      mass index and hypertension in a cohort of 4th-grade students. Students who were
      overweight or at risk for overweight when in the 1st grade were over 4 times more
      likely to be overweight or at-risk-for overweight in the 4th grade than were
      students who were not overweight or not at risk for overweight when in the 1st
      grade. Students who were overweight or at risk for overweight when in the 1st
      grade were approximately 3 times more likely to be hypertensive or
      prehypertensive in the 4th grade than were students who were not overweight or
      not at risk for overweight when in the 1st grade.

PMID- 19399686
TI  - Associations of various family characteristics and time use with children's body
      mass index.
AB  - This study used multiple regression models to estimate associations of various
      family characteristics and time use with the body mass index (BMI) z-scores of
      734 boys and 725 girls aged 5-18y from the Panel Study of Income Dynamics Child
      Development Supplement 2003. The strongest relationship in the data was between
      the BMI of the head of household and a child's BMI z-score (p < 0.001). Time
      spent sleeping, performing sedentary behaviors, and participating in physical
      activities was not associated with a child's BMI z-score. This suggests that a
      family-oriented approach to prevent and treat childhood and adolescent overweight
      is required.

PMID- 19399687
TI  - Public and community health nursing interventions with vulnerable primary care
      clients: a pilot study.
AB  - The primary aim of this pilot study was to test the effects of public/community
      health nursing (P/CHN) home visitation and a mutual goal-setting intervention on
      the intensity of need for nursing care levels and health behavior of vulnerable
      primary care clients. A secondary aim was to describe the content of client
      health behavior improvement goals. Eighty clients, aged 19-93 years, judged by
      their primary care providers to have unmet health needs were referred for P/CHN
      services. A quasi-experimental design was used, with the intervention group
      receiving the mutual goal-setting intervention. Senior baccalaureate nursing
      students, guided by faculty case managers, provided home visitation nursing care
      and the mutual goal-setting intervention. No significant effects of mutual goal
      setting were found, however the 10-week P/CHN home visitation intervention was
      found to have significant positive effects on intensity of need for nursing care
      levels and health behaviors. Also, preferred client health improvement goals for
      this population are described. Several implications for P/CHN practice and
      research are discussed.

PMID- 19399690
TI  - The late adverse events of rituximab therapy--rare but there!
AB  - Rituximab, an anti CD20 monoclonal antibody, has now become a cornerstone in the
      treatment of many CD20 positive hematological malignancies and a variety of
      autoimmune disorders. In contrast to the acute allergic and cytokine associated
      reactions, late adverse events of rituximab are indeed uncommon but at the same
      time probably under-reported. In this review, we detail late adverse events
      reported since its use in hemato-oncological neoplasias and other disorders.
      These adverse events include the development of late-onset neutropenia, defects
      of immune reconstitution with associated immune compromise, infections,
      progressive multifocal leukoencephalopathy, reactivation of hepatitis, intestinal
      perforation and interstitial pneumonitis. Possible mechanisms involved in
      rituximab-associated complications and the pathogenesis of these adverse effects
      are reviewed and discussed. Evidence based graded recommendations for the
      management of these adverse effects are proposed.

PMID- 19399691
TI  - The Spt-Ada-Gcn5-acetyltransferase complex interaction motif of E2a is essential
      for a subset of transcriptional and oncogenic properties of E2a-Pbx1.
AB  - The oncogene E2a-Pbx1 is formed by the t(1;19) translocation, which joins the N
      terminal transactivation domain of E2a with the C-terminal homeodomain of PBX1.
      The goal of this work was to elucidate the mechanisms by which E2a-Pbx1 can lead
      to deregulated target gene expression. For reporter constructs it was shown that
      E2a-Pbx1 can activate transcription through homodimer elements (TGATTGAT) or
      through heterodimer elements with Hox proteins (e.g. TGATTAAT). We show a novel
      mechanism by which E2a-Pbx1 activates transcription of EF-9 using a promoter in
      intron 1 of the EF-9 gene, resulting in an aminoterminal truncated transcript.
      Our results indicate that the LDFS motif of E2a is essential for the
      transactivation of EF-9, but dispensable for transactivation of fibroblast growth
      factor 15. The E2a LDFS motif was also essential for proliferation of NIH3T3
      fibroblasts but was dispensable for the E2a-Pbx1-induced differentiation arrest
      of myeloid progenitors.

PMID- 19399693
TI  - Implementation of responsiveness to intervention in early education settings.
AB  - This article provides an overview of how response to intervention (RTI) may be
      used effectively within early childhood settings. Discussion is organized to
      address such issues regarding RTI implementation as (1) how to design and
      implement a high-quality Tier 1 learning environment that systematically improves
      children's language and literacy outcomes, (2) how to design and implement a high
      quality Tier 2 supplemental learning intervention that systematically improves
      the language and literacy outcomes of children who are unresponsive to Tier 1,
      and (3) how to design and implement a comprehensive and cohesive assessment
      system that appropriately identifies children who show inadequate response to the
      Tier 1 and Tier 2 learning opportunities. A model for implementing RTI using the
      supplemental curriculum by Justice and McGinty, READ IT AGAIN-PREK! (2008), is
      presented. This tool was developed to meet the needs of early childhood programs
      as they seek to implement RIA in a cost-effective and scalable manner.

PMID- 19399694
TI  - Applications of responsiveness to intervention and the speech-language
      pathologist in elementary school settings.
AB  - This article addresses ways in which speech-language pathologists can play a
      proactive and substantive part in school-wide language and reading disability
      prevention and intervention efforts within the responsiveness to intervention
      framework. Within a collaborative working paradigm, specific student-focused
      instructional targets are presented in the areas of oral language, metacognition,
      and reading comprehension. A discussion of professional development focuses on
      enhancing teacher-student communication interaction, a critical yet often
      undervalued component of teacher training.

PMID- 19399695
TI  - Speech-language pathologists as primary contributors to response to intervention
      at the secondary level.
AB  - Response to intervention (RTI) is currently receiving attention at the middle and
      high school levels. Although many academic and behavioral needs in secondary
      schools may warrant an RTI initiative, lack of literacy skills in adolescents is
      among the most important because language and literacy are foundational to
      curriculum learning. Speech-language pathologists (SLPs) have much to offer
      secondary RTI initiatives, given their expertise in language and literacy.
      Therefore, they need to become primary contributors. This article addresses
      several important conditions necessary to bring SLPs into the forefront with RTI
      at the secondary level by discussing (1) having a common understanding of RTI
      that is being implemented differently across the country; (2) understanding the
      rationale for adopting RTI at the secondary level; (3) defining unique
      contributions of SLPs that add value to RTI initiatives in middle and high
      schools; (4) exploring what it takes for SLPs to become involved, including
      attention to curriculum and literacy, changing the perceptions of others
      regarding the roles of SLPs, restructuring of delivery models, and replacing a
      caseload approach to service delivery with a workload approach; (5) establishing
      productive working relationships among professionals in secondary schools; and
      (6) exerting leadership to move forward in RTI involvement.

PMID- 19399696
TI  - Response to intervention and English-language learners: instructional and
      assessment considerations.
AB  - This article presents issues associated with the implementation of a three-tier
      response to intervention (RTI) approach with English-language learners (ELLs).
      Instructional and assessment considerations are discussed particularly as they
      pertain to issues of language and literacy development. Opportunities for
      collaboration among bilingual education, English as a second language, and
      general education teachers, and speech-language pathologists are identified. In
      addition to effective Tier 1 and Tier 2 interventions, prerequisites to the
      success of RTI approaches for ELLs are discussed, including school climate and
      effective instruction.

PMID- 19399697
TI  - Response to intervention and dynamic assessment: do we just appear to be speaking
      the same language?
AB  - In this article we compare and contrast two frameworks for assessment that appear
      to share the same language yet produce very different approaches and outcomes:
      response to instruction/intervention and dynamic assessment. We explore the
      nature of each, elaborate their similarities and differences, and suggest there
      are sufficient similarities in goals and principles that the two should be melded
      into a single model that promotes development of learning competence in children.
      We specifically consider the relevance of the combined model of response to
      intervention plus dynamic assessment for professionals involved with language
      development and disorders.

PMID- 19399698
TI  - [Gender differences in psychosocial variables in inpatient orthopedic
      rehabilitation of chronic low back pain].
AB  - As females are more often affected by chronic low back pain and psychological
      impairments than males, it can be assumed that females are more prone to develop
      chronic pain and have a special need for psychological treatment in orthopedic
      rehabilitation of chronic low back pain. In realizing a one-factorial design,
      effects of gender on psychosocial measures were examined in a consecutive sample
      of N=431 patients with chronic low back pain prior to rehabilitation. Females
      showed more psychological strain and pain-related impairments than males.
      Furthermore, the development of chronicity was more advanced in women than men.
      Evidence suggests increased needs for psychosocial interventions in females
      compared to males in inpatient orthopedic rehabilitation of chronic low back
      pain. Additionally, the necessity of a tailored allocation to specific
      psychological interventions in the rehabilitation of chronic low back pain is
      emphasized.

PMID- 19399699
TI  - [Students' attitudes towards psychotherapy: changes after a course on psychic
      functions in health and illness].
AB  - OBJECTIVES: Little is known about the attitude of medical students towards
      psychotherapy and the influence of lectures on psychotherapy during the medical
      curriculum on these attitudes. METHODS: 2 years in a row, medical students of the
      Medical University of Vienna in their fourth academic year were asked regarding
      their attitudes, connotations and associations towards psychotherapy before and
      after a 5-week psychotherapeutic course. RESULTS: The attitudes of the medical
      students were predominantly positive, while some prejudices could be found. The
      students' sex and prior experience with psychotherapy influenced their attitudes.
      The attitudes turned out to be relatively resistant to change through teaching.
      CONCLUSIONS: Reasons for the small influence of the training program on the
      students' attitudes and possible improvements of the course (small lecture
      groups) are discussed.

PMID- 19399700
TI  - [Factor structure and psychometric properties of the ICD-10-Symptom-Rating (ISR)
      in samples of psychosomatic patients].
AB  - The ICD-10-Symptom-Rating (ISR) is a self-rating questionnaire for patients.
      According to its conceptualization, the instrument was developed to closely
      represent the syndrome structure of the ICD-10 while assessing the extent of
      psychological distress an individual suffers from. The results of different
      factor analyses testing the postulated syndrome structure as well as item and
      scale characteristics are reported here. Data was collected from a consecutive
      sample of 1 057 psychosomatic patients of the University Hospital Charite Berlin.
      Evaluation of the dimensional structure of the questionnaire included exploratory
      and confirmatory factor analyses each computed with a randomized half of the
      sample. Multi-Sample-Analyses with different subgroups of the sample were
      performed to test the stability of the factor structure. The individual factors
      were constituted by the postulated syndrome units of the ICD-10 involving a high
      and uniform distribution of accounted variance. They also proved themselves
      satisfactorily stable over the different subsamples. The scales showed a high
      degree of internal consistency with relatively small gender and age effects,
      while psychological disorders had a large effect on the means of the scales.
      Taking a perspective of test theory, the ICD-10-Symptom-Rating is in accordance
      with the syndrome structure of the ICD-10 and suitable for the assessment of
      psychological symptoms. Other aspects pertaining to the reliability and validity
      of the ISR remain to be proven in future research.

PMID- 19399701
TI  - [Increased prevalence of problematic alcohol consumption in university students].
AB  - OBJECTIVE: To compare the prevalence rates of problematic alcohol consumption in
      students and in the general population. METHODS: A sample of students (n=1 115)
      and a population sample (n=631) were assessed with the Patient Health
      Questionnaire (PHQ). The PHQ probes for problematic alcohol consumption with five
      questions. An "alcohol syndrome" is suspected if at least one of these indicators
      is present. RESULTS: The alcohol syndrome was present more frequently among
      students than in the population sample (30,1% versus 8,1%). The odds ratio,
      adjusted for age, gender and education, was OR=3,7. However, when the five
      indicators were analysed separately, only two of them were significantly more
      frequent in students than in the comparison sample. Both indicate a neglect of
      duties as a consequence of alcohol consumption. CONCLUSIONS: Intervention
      strategies aimed at students' alcohol consumption should focus on binge drinking
      and the risks associated with this problematic form of alcohol consumption.

PMID- 19399702
TI  - [Who has more anxiety concerning a shortened life span: terminal cancer patients
      or those in curative therapy?].
AB  - The aim of this study is to investigate whether there is a difference in the
      amount of fear of the advancement (progression) and return (relapse) of cancer
      shown by terminal cancer patients and those in curative therapy. The cohort
      consists of 291 rehabilitation patients, main diagnoses were colonic/rectal-,
      breast- and prostate cancer. The patients were questioned using the fear of
      progression questionnaire (PA-F-KF) and a Five-Item Fear of Relapse/Recurrence
      Scale. Patients in palliative care and those in curative therapy are equally
      fearful of the disease progressing. When comparing both groups for fear of
      relapse however, those patients in palliative care are more anxious. This
      apparently paradoxical result can be seen as being an expression of the highly
      debilitating fear experienced by terminally ill cancer patients. Simultaneously,
      patients try to keep up their hope by unconsciously reinterpreting the actual
      progress of the disease as being a potential relapse.

PMID- 19399703
TI  - A neonate with umbilical arteriovenous malformation showing hemorrhagic shock
      from massive umbilical hemorrhage.
AB  - We describe herein the case of a 3-day-old male neonate with umbilical
      arteriovenous malformation showing umbilical hemorrhage. The patient was born
      after 38 weeks and 3 days of gestation with a birth weight of 2784 g. Sudden
      massive umbilical hemorrhage occurred on day 3. Cardiopulmonary arrest developed,
      but the patient was successfully rescued by immediate cardiopulmonary
      resuscitation. An umbilical venous catheter was inserted for blood access.
      However, umbilical hemorrhage continued and hemostasis was difficult. Congenital
      bleeding disorders were excluded based on laboratory findings. Ultrasonography on
      day 15 revealed a mass with rich blood supply directly under the umbilicus.
      Umbilical arteriovenous malformation was suspected from abdominal contrast
      enhanced computed tomography on day 17. Excision of the arteriovenous
      malformation was performed on day 29. The mass was connected to three arteries
      including the umbilical arteries, with the umbilical vein flowing out from the
      mass. Umbilical arteriovenous malformation was diagnosed from evidence during the
      operation and pathological findings. Umbilical arteriovenous malformations are
      rare and often discovered by heart failure symptoms, but rare cases present with
      umbilical bleeding, as in this report. Umbilical arteriovenous malformation must
      be taken into consideration as along with congenital bleeding disorders when
      massive umbilical hemorrhage is identified.

PMID- 19399704
TI  - Increased preeclampsia in mothers delivering very low-birth-weight infants
      between 1994 and 2006.
AB  - We sought to determine if there has been any change in the proportion of mothers
      with preeclampsia in a sample of very low-birth-weight (VLBW) infants over time.
      We performed a retrospective cohort study. Study sample included infants with
      birth weights 1500 g or less cared for from July 1994 to July 2006 ( n = 2045)
      from a single level 3 neonatal intensive care unit in Delaware. The main outcome
      examined was the occurrence of maternal preeclampsia over the study time. The
      proportion of mothers with preeclampsia delivering VLBW infants increased over
      time. After controlling for potential confounding variables, the odds of maternal
      preeclampsia were increased (1.3, 95% confidence interval 1.2 to 1.5) in infants
      born between 2003 and 2006 compared with those born between 1994 and 1997. In our
      population of VLBW infants, the proportion of mothers with the diagnosis of
      preeclampsia increased over time. From our investigation, we cannot determine if
      the increase in the proportion of mothers with preeclampsia is related to a true
      increase in the disease, changes in diagnostic surveillance, or other factors.

PMID- 19399705
TI  - Two dose regimens of nifedipine for management of preterm labor: a randomized
      controlled trial.
AB  - We compared two dose regimens of tocolytic oral nifedipine. Women with singleton
      pregnancies admitted in preterm labor (24 to 34 weeks) were randomized to high
      dose (HD) nifedipine ( N = 49; 20 mg loading dose, repeated in 30 minutes, daily
      120 to 160 mg slow-release nifedipine for 48 hours followed by 80 to 120 mg daily
      until 36 weeks) or low-dose (LD) nifedipine ( N = 53; 10 mg, up to four doses
      every 15 minutes, daily 60 to 80 mg slow-release nifedipine for 48 hours followed
      by 60 mg daily until 36 weeks). Uterine quiescence at 48 hours (primary outcome);
      delivery at 48 hours, 34 and 37 weeks; and recurrent preterm labor were similar.
      Gestational age at delivery was higher in HD (36.0 +/- 2.8 versus 34.7 +/- 3.7
      weeks, P = 0.049). Rescue treatment was needed more in LD (24.5 versus 50.9%,
      odds ratio = 0.3; 95% confidence interval 0.1 to 0.7). Maternal adverse effects,
      birth weight, intensive care nursery admission, and composite neonatal morbidity
      were similar. However, neonatal mechanical ventilation was needed less and
      nursery stay was shorter in HD. HD nifedipine does not seem to have an advantage
      over LD in achieving uterine quiescence at 48 hours. Further studies should
      address the optimal dose and formulation of tocolytic nifedipine.

PMID- 19399706
TI  - Fetal heart rate patterns in neonatal hypoxic-ischemic encephalopathy:
      relationship with early cerebral activity and neurodevelopmental outcome.
AB  - Despite widespread use of fetal heart rate monitoring, the timing of injury in
      hypoxic-ischemic encephalopathy (HIE) remains unclear. Our aim was to examine
      fetal heart rate patterns during labor in infants with clinical and
      electroencephalographic (EEG) evidence of HIE and to relate these findings to
      neurodevelopmental outcome. Timing of onset of pathological cardiotocographs
      (CTGs) was determined in each case by two blinded reviewers and related to EEG
      grade at birth and neurological outcome at 24 months. CTGs were available in 35
      infants with HIE (17 mild, 12 moderate, 6 severe on EEG). Admission CTGs were
      normal in 24/35 (69%), suspicious in 8/35 (23%), and pathological in 3/35 (8%).
      All CTGs developed nonreassuring features prior to delivery. Three patterns of
      fetal heart rate abnormalities were seen: group 1, abnormal CTGs on admission in
      11/35 (31%); group 2, normal CTGs on admission with gradual deterioration to
      pathological in 20/35 cases (57%); and group 3, normal CTGs on admission with
      acute sentinel events in 4/35 (11.5%). The median (interquartile range) duration
      between the development of pathological CTGs and delivery was 145 (81, 221)
      minutes in group 2 and 22 (12, 28) minutes in group 3. There was no correlation
      between duration of pathological CTG trace and grade of encephalopathy (R = 0.09,
      P = 0.63) or neurological outcome (P = 0.75). However, the grade of
      encephalopathy was significantly worse in group 3 (P = 0.001), with a trend to
      worse outcomes. The majority of infants with HIE have normal CTG traces on
      admission but develop pathological CTG patterns within hours of delivery. More
      severe encephalopathy was associated with normal admission CTG and acute sentinel
      events shortly before delivery.

PMID- 19399707
TI  - Prenatal diagnosis of triploidy associated with holoprosencephaly: a case report
      and review of the literature.
AB  - We sought to identify risk factors of prenatal presentation of holoprosencephaly
      associated with triploidy. A case report is presented with review of the
      literature performed using the PubMed database. The latest search was done in
      June 2008. Literature review showed 11 reports with a total of 15 cases of
      holoprosencephaly associated with triploidy. The mean maternal age at diagnosis
      was 27 +/- 4.9 years, and the mean gestational age at diagnosis was 13.6 +/- 3.3
      weeks. Triploidy was mainly associated with the alobar type of holoprosencephaly.
      Only 3 (20%) cases had associated placental abnormalities. In all cases, the
      pregnancy was terminated. The latest gestational age at which termination was
      performed was 23 weeks. Facial abnormalities were the most common associated
      feature (66.6%). The association of triploidy with holoprosencephaly is very
      rare. This association does not seem to be related to maternal age. It is mainly
      associated with alobar holoprosencephaly. Diagnosis is possible during the first
      trimester. Fetuses can survive up to the third trimester.

PMID- 19399708
TI  - Incidental finding of pseudomyxoma peritonei at primary cesarean section.
AB  - Primary appendiceal carcinoma is extremely rare and is found in approximately 1%
      of appendectomy specimens. When cancer is present, the most frequent histology is
      mucinous adenocarcinoma. Neoplasms of the appendix that secrete mucin such as
      adenocarcinoma may rupture, leading to intraperitoneal seeding of the peritoneum
      and producing the clinical picture of pseudomyxoma peritonei (PMP). PMP is
      characterized by mucin-producing neoplastic cells that have seeded the peritoneum
      from the ruptured viscous and continue to secrete copious amounts of gelatinous
      material that accumulates in the abdomen producing the characteristic "jelly
      belly." A review of the medical literature revealed no cases of PMP diagnosed at
      time of cesarean section. A previously healthy gravida 5, para 3 underwent
      cesarean section. Upon opening of the peritoneum, copious amounts of gelatinous,
      yellow-tinged mucoid material was noted. A general surgeon was consulted, and
      grossly necrotic-appearing appendix was noted. The patient underwent appendectomy
      with right hemicolectomy. Pathology showed well-differentiated mucinous
      adenocarcinoma of the appendix. PMP is associated with gastrointestinal and
      ovarian carcinomas. Although somewhat rare, these cancers may occur in pregnancy.
      Because nonspecific abdominal pain and increasing abdominal girth are common in
      pregnancy, patients' complaints may go ignored. Early diagnosis of a potentially
      life-threatening disease requires that clinicians expand the differential
      diagnosis and consider the possibility of a malignant neoplasm presenting in the
      pregnant female.

PMID- 19399709
TI  - [Tumour-like lesions of the orbit - clinical symptoms, difficulties in
      differentiation and options for therapy].
AB  - Tumour-like lesions are very rare entity among orbital diseases. Between 1996 and
      2007, 83 patients with orbital disorders were treated and three of them
      complained about different tumour-like lesions: giant cell granuloma,
      eosinophilic granuloma and fibrous dysplasia. Because of the considerable
      increase of functional disorders and tumour growth, all of the patients underwent
      surgical treatment. In this paper we describe the clinical symptoms, diagnostics
      and the methods of therapy for each of the lesions. The results shows that the
      preoperative neuro-ophthalmological examination as well as radiological imaging
      are necessary to assess the motility, visual field, vision, eye ball dislocation
      and to plan the surgical strategy. In terms of this descriptive character of the
      paper, we hope to submit some relevant information in order to improve the
      diagnostics and therapeutic procedures for tumour-like lesions of the orbit.

PMID- 19399710
TI  - [Selective thrombophilia screening of young patients with retinal vein
      occlusion].
AB  - BACKGROUND: The potential impact of coagulation abnormalities on retinal vascular
      occlusive diseases, individually and in combination with cardiovascular risk
      factors, remains unclear. PATIENTS AND METHODS: In a prospective case-control
      study a cohort of 74 young patients with central, hemicentral or branch retinal
      vein occlusion (RVO) (<or= 45 years at the time of the RVO or a previous
      thromboembolic event) and 74 subjects matched for age and sex were prospectively
      screened for thrombophilic risk factors. RESULTS: Overall, thrombophilic defects
      were found to be present in 38 of the 74 patients (51.4 %) and in 8 of 74 (10.8
      %) controls (p < 0.0001). We found a strong association between the presence of
      thrombophilic disorders and a family history of thromboembolism (p < 0.0001).
      Patients without cardiovascular risk factors had a statistically significant
      higher frequency of coagulation disorders than patients with these risk factors
      (p = 0.0025). CONCLUSIONS: Our results indicate that thrombophilic disorders are
      associated with the development of retinal vein occlusion. Selective screening of
      young patients, patients with a personal or family history of thromboembolism,
      and patients without cardiovascular risk factors may be helpful in identifying
      retinal vein occlusion patients with thrombophilic defects.

PMID- 19399711
TI  - [Results of low-vision rehabilitation in vision impaired patients].
AB  - PURPOSE: Diseases of the retina, the optic nerve and the cornea may lead to a non
      treatable loss of central vision. We report on low vision rehabilitation in 100
      vision impaired patients. METHODS: Low vision rehabilitation was performed in 100
      consecutive patients (61 % AMD, 23 % diabetic retinopathy, 16 % other diseases).
      Most of the patients were between 70 and 90 years old (78 %). In 62 cases we
      fitted optic systems for visual rehabilitation of the far distance (Galilei
      systems 54; Kepler systems 8), in additional 54 of them we fitted optic systems
      for the reading distance (additional lens 40; others 14; e. g. magnifier,
      television reader) and in 38 patients we fitted optic systems for visual
      rehabilitation only of the reading distance (magnifier 21, reading glasses with
      higher refraction and additional prism system 17). RESULTS: In 62 patients with
      low vision fitted with a system for the far distance we reached an increase of
      the visual acuity of more than one line in 95 %. In all 92 patients fitted with a
      system for the reading distance the reading of newspaper letters was possible. In
      8 patients we could not fit a low vision systems due to handling difficulties.
      CONCLUSIONS: We could reach a satisfactory improvement of visual acuity in more
      than 90 % of the patients fitted for the far and the reading distance. Especially
      in elderly, vision impaired patients significant improvements in overall quality
      of life and specific areas of daily living are possible.

PMID- 19399712
TI  - [Pilomatrixoma of the ocular adnexae: clinical and histologic analysis (13
      cases)].
AB  - BACKGROUND: Pilomatrixoma (calcifying epithelioma of Malherbe) is a rare benign
      tumour originating from the matrix of the hair root. In this study, we evaluated
      the clinical and histopathological characteristics of all the respective tumour
      specimens submitted to our laboratory since 1997. PATIENTS/MATERIALS AND METHODS:
      We reviewed the clinical and histologic findings of 13 pilomatrixomas localised
      to the ocular adnexae. Paraffin sections were stained with H&E and PAS and, in
      addition, immunohistochemistry was performed using markers for macrophages
      (CD68), for proliferative activity (Ki67), and for proliferation/apoptosis
      (CAS/CSE1L). RESULTS: All 13 pilomatrixomas were of reddish-livid colour and
      localised on the upper eyelid and/or near the eyebrow. The patients ages ranged
      from 4 to 84 years without preference for either gender. In 3 cases the correct
      diagnosis was made intraoperatively, while no pilomatrixoma was diagnosed prior
      to surgery. The most frequent false diagnoses were retention cyst (n = 3),
      atheroma (n = 2), and abscess (n = 2). There was no tumour recurrence in any of
      the cases within the time period presented. All 13 pilomatrixomas demonstrated
      the characteristic histology with areas of basophilic islands, shadow cells,
      calcification and a chronic granulomatous inflammation with foreign body giant
      cells in varying amounts. Immunhistochemical staining with anti-Ki67 and anti
      CAS/CSE1L indicated a regular cellular maturation of the basophilic cells. No
      correlation was found between any of the histological or immunohistochemical
      markers and clinical parameters such as size, age and gender of the patient and
      duration of tumour presence prior to surgery. CONCLUSIONS: This case series
      represents one of the largest published so far, and underscores that
      pilomatrixoma can appear at any age. While it is usually not recognised
      clinically, it should be considered in the differential diagnosis especially for
      tumours of the upper eyelid. Our immunohistochemical findings support the
      basically benign nature of a pilomatrixoma but also point to the chronic
      inflammatory stimulus that can lead to complications after incomplete removal.

PMID- 19399713
TI  - [Spontaneous improvement of visual acuity in adult amblyopia after functional
      loss in the non-amblyopic eye?].
AB  - BACKGROUND: The prognosis of functional improvement after vision loss in the non
      amblyopic eye in adulthood is important for counselling of the patients, but
      uncertain for a number of reasons. Our study focuses on two aspects. Firstly, a
      questionnaire was developed asking ophthalmologists and orthoptists for their
      opinion about the chances of significant spontaneous improvement; secondly,
      patient data were analysed with respect to acuity data acquisition and
      documentation as reasons for uncertainty concerning the prognosis. MATERIALS AND
      METHODS: In the context of a project about age limits of amblyopia treatment, a
      questionnaire was developed which comprised also an item about the estimation of
      the prognosis after loss of vision in the non-amblyopic eye. It was distributed
      to ophthalmologists and orthoptists, and the answers were analysed in connection
      with two large, published studies about this topic . Furthermore, acuity data of
      three adult amblyopes were analysed after loss of function in the non-amblyopic
      eye. RESULTS: The questionnaire was answered by 109 ophthalmologists and 128
      orthoptists, all working in Germany. Almost 50% of the answers concerning the
      chances of spontaneous improvement were in agreement with the data of the two
      published studies, which stated that the chances of spontaneous improvement were
      10% or 17.4%, respectively. More than 25% of the answers underestimated the
      chances for spontaneous improvement (answer: 0 to 5%). On the other hand, a
      number of orthoptists and ophthalmologists estimated the chances much too
      optimistically, some anticipating more than a 60% chance of spontaneous
      improvement. The analysis of the patient data showed that both acquisition and
      documentation of acuity data gave reasons for uncertainties concerning the
      prognosis for visual acuity. CONCLUSIONS: In addition to new ways of assessing
      treatment compliance and quality of life, knowledge about the opinion of the
      treating personnel concerning various aspects of a disease may lead to more
      evidence-based treatment. In amblyopic patients, the inclusion of certain details
      into the documentation (type and separation of the optotypes, optical correction)
      may be essential.

PMID- 19399714
TI  - [Opinions of German-speaking experts about strabismus surgery].
AB  - BACKGROUND: There is a lack of studies about how to proceed surgically in rare
      strabismus diseases. It was the aim of this study to interview experienced German
      speaking strabismologists about how they perform surgery in rare but also some
      frequent strabismic conditions. The focus was on the choice of the technique, the
      timing, and the dosage. METHOD: A validated questionnaire was sent to 11
      experienced strabismus surgeons. It contained questions about the following
      topics: congenital fibrosis syndrome, Jaentsch-Brown syndrome, intermittent
      exotropia, maximum dosage for rectus muscle surgery, Kestenbaum surgery, sixth
      nerve palsy, heterophorias, myokymia of the superior oblique muscle, thyroid
      endocrine orbitopathy, dissociated vertical deviation, adjustable sutures,
      advancement of previously recessed rectus muscles, retroequatorial myopiexia, and
      congenital esotropia. RESULTS: Ten experts answered the questionnaire (91%).
      There was a large consent for many topics. However, for many procedures there was
      disagreement about the dosage and the timing. Since some questions addressed rare
      diseases and many strabismologists use only certain types of surgical procedures,
      some questions could only be answered by a few surgeons. CONCLUSIONS: German
      speaking strabismologist show a large consensus about the type of surgical
      procedure to use, but often disagree about the dosage and timing of the
      operation.

PMID- 19399715
TI  - [Polymorphisms of complement factor genes and age-related macular degeneration in
      a German population].
AB  - BACKGROUND: An association of the Tyr402His variant of the complement factor H
      (CFH) gene with age-related macular degeneration (AMD) has been shown in several
      Caucasian populations, while studies for an association with other single
      nucleotide polymorphisms (SNP) of complement system genes have produced
      inconsistent results. We examined the distribution of several SNPs of complement
      system genes (CFH, C 2, C 3, factor B) in patients with exsudative AMD and
      healthy controls. PATIENTS/MATERIALS AND METHODS: 226 patients with exsudative
      AMD and 179 controls without AMD were included. Genomic DNA was extracted from
      saliva samples. RESULTS: A significant association with exsudative AMD was found
      only for SNP rs1061170 (Y402 H) in the CFH gene. For rs1047286 (P292L) and
      rs2230199 (R102G) in the C 3 gene, rs547154 (IVS10) and rs9332739 (E318D) in the
      C 2 gene and rs4151667 (L9 H) in CFB gene, no associations with exsudative AMD
      were found. CONCLUSIONS: We have replicated an association of the Y 402 H variant
      with exsudative AMD in our population. Although variants R 102G, IVS10, E 318D
      and L 9 H have been shown to be associated with AMD in earlier studies, we could
      not confirm these findings. The results show that AMD has variable association
      patterns with rare variants in different populations.

PMID- 19399716
TI  - [Cut quality of a new femtosecond laser system].
AB  - OBJECTIVE: The aim of this study was to evaluate the cut quality and the cellular
      damage when using a new 200 kHz femtosecond laser. METHODS: 20 porcine eyes and 3
      human eyes, not suitable for transplantation, were used for this study. The
      WaveLight UltraFlap femtosecond laser was used for flap creation. The surface of
      the cornea, the structure and ultrastructure of the corneal cells and stroma were
      evaluated thoroughly using light microscopy (HE-, PAS- and Picrosirius red
      staining), transmission electron microscopy (TEM), and scanning electron
      microscopy (SEM). RESULTS: In all eyes, the flap could be lifted very easily and
      the flap appeared very smooth. Structural and ultrastructural evaluation with
      light and transmission electron microscopy on epithelium and endothelium showed
      no side effects of the laser application. The area around the flap cut was
      minimally affected and the keratocytes and collagen fibres showed minimal
      alteration due to laser treatment. Scanning electron microscopy revealed in all
      cases smooth surfaces and precise sidecuts. CONCLUSIONS: Precise corneal flaps
      can easily be created with this new femtosecond laser. At the same time, no
      structural and thermal side effects on corneal epithelium, stroma and endothelium
      appeared. Hence with this new femtosecond laser corneal flaps could be created
      easily without noteworthy side effects.

PMID- 19399717
TI  - [Insulation characteristics of transport containers for organ cultured donor
      corneas under different ambient temperatures].
AB  - BACKGROUND: The aim of this study was to evaluate the ability of different
      transport containers to maintain an inside temperature between +10 and +40
      degrees C, which is supposed to be safe for organ cultured donor corneas in
      dextran containing culture media, for a period of 24 hours at ambient
      temperatures of -10, 0, +10 and +50 degrees C. MATERIALS AND METHODS: 3
      containers were tested: 1. Styrofoam box with 2.5 cm thick walls (Graft-tec,
      AL.CHI.MI.A., Padova, Italy). 2. Thermos jug 0.5 litre (Primus, Solna, Sweden), a
      double walled metal jug. 3. ThempShell-22 degrees (VWR International, Darmstadt,
      Germany), a box of gel filled plastic elements. The containers were exposed to 
      10, 0, +10 and +50 degrees C for 24 hours each. A continuous temperature
      recording of the ambient and internal environments was performed using electronic
      thermometers (Mini Intelligent Logger, Escort). RESULTS: The inside temperature
      of the styrofoam box reached the outside temperature level after 80 - 230 min for
      all tested settings. The Thermos jug reached the outside temperature
      approximately after 5 hours. In contrast, the inside temperature of the TempShell
      22 degrees CC was at -10 degrees C outside temperature 21 degrees C after 6
      hours, 19 degrees C after 12 hours and 12 degrees C after 24 hours. At an ambient
      temperature of 0 and +10 degrees C the inside temperature of the TempShell-22
      degrees C was 19.2 and 17.8 degrees C respectively after 24 hours. An ambient
      temperature of + 50 degrees C led to an inside temperature of the TempShell-22
      degrees C of 30.5 degrees C after 6, 38.3 degrees C after 12 hours and 47.0
      degrees C after 24 hours. CONCLUSIONS: A standard Styrofoam box with 2.5 cm thick
      walls and the tested thermos jug are not suitable to assure a safe temperature
      range. The TempShell-22 degrees C assures a safe temperature range for low
      ambient temperatures (-10 to +10 degrees C) for at least 24 hours and for an
      ambient temperature of +50 degrees C for at least 10 hours.

PMID- 19399718
TI  - Pharmacokinetics and tissue distribution of dodeca-2E,4E,8E,10E/Z-tetraenoic acid
      isobutylamides after oral administration in rats.
AB  - The present study investigated the pharmacokinetics and tissue distribution of
      dodeca-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides (tetraenes), the main
      alkamides in ECHINACEA preparations, in rats after a single oral dose
      administration of 2.5 mg/kg. Plasma, liver and 4 different brain regions
      (hippocampus, cerebral cortex, striatum and cerebellum) were collected after 8,
      15, 30 minutes and 1, 2, 3 and 6 hours after oral dosing. Plasma and tissue
      concentrations were determined by a rapid (5 min) liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method with benzanilide as internal standard (IS)
      using the respective [M-H] (+) ions, M/Z = 248/152 for the dodeca-2 E,4 E,8 Z,10
      E/ Z-tetraenoic acid isobutylamides and M/Z = 198/105 for the IS. The lipophilic
      constituents were rapidly absorbed, with a T (max) of 15 minutes, distributed and
      appeared in the brain already within 8 minutes. The total amount of tetraenes in
      different brain parts was calculated as AUC (0-infinity) (range: 1764-6192 min x
      ng/g) and compared to the concentrations found in plasma (794 min x ng/mL) and
      liver tissues (1254 min x ng/g). The C (max) in plasma was 26.4 ng/mL, while the
      C (max) in the different brain regions varied between 33.8 ng/g and 46.0 ng/g. In
      the striatum the highest concentration and the longest elimination half-life of
      253 minutes with a mean residence time of 323 minutes was detected. The results
      demonstrate that the dodeca-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides
      are bioavailable in rats with a rapid passage across the blood-brain barrier.

PMID- 19399719
TI  - A reliable and aesthetic technique for cephalic vein harvest in DIEP flap
      surgery.
AB  - The need for a secondary source of venous drainage in deep inferior epigastric
      artery perforator flaps is common, with the cephalic vein commonly utilized as an
      alternative venous recipient vessel. In using the cephalic vein, previous studies
      have described the deltopectoral groove or the infraclavicular fossa as the site
      for harvest. We describe the use of an anterior axillary skin crease, which can
      improve aesthetic outcome, reduce the time needed for harvest, enable a greater
      length of vein to be transposed, and minimize surgical insult to the upper
      breast/chest wall. An anterior axillary-line skin fold can be used as the site
      for cephalic vein harvest, and using the methodology described, the technique can
      be fast and highly reliable and result in a final scar that is barely visible.

PMID- 19399720
TI  - [GnRH antagonists--a new therapy option for advanced prostate cancer].
AB  - At present medical castration employing luteinising hormone releasing hormone
      (LHRH) agonists is the standard of care for patients with advanced prostate
      cancer. LHRH agonists suppress the synthesis of testosterone to a castration
      level. In contrast to surgical castration, medical castration is reversible.
      However LHRH agonists induce an initial increase of the testosterone level. This
      so-called testosterone surge leads to tumour growth and increases the disease
      specific complaints, known as flare phenomena. It may be possible that the
      overall survival of these patients is deteriorated. In contrast, gonadotrophin
      releasing hormone (GnRH) antagonists do not induce a testosterone surge and the
      level of testosterone decreases as rapidly as that known from a surgical
      castration.

PMID- 19399721
TI  - [Adverse drug effects: involvement of physicians demanded].

PMID- 19399723
TI  - [Effect of tigecycline on selected multiresistant bacteria].
AB  - INTRODUCTION: Currently, one of the most serious problems in medicine is the
      increasing resistance of pathogenic bacteria to antimicrobial drugs. Bacterial
      resistance may potentially be solved in particular by decreasing the consumption
      of antibiotics and increasing the quality of their use. Equally important,
      however, is the development of new antimicrobial drugs and their use in clinical
      practice. One of the new antibiotic agents is tigecycline of the glycylcycline
      group. The presented work aimed at assessing its in vitro effect on selected
      multiresistant bacteria. MATERIAL AND METHODS: Clinical samples were collected
      from patients hospitalized in the University Hospital Olomouc to isolate ESBL-
      and AmpC beta-lactamase-producing enterobacteria, methicillin-resistant
      Staphylococcus aureus (MRSA) strains and vancomycin-resistant enterococci (VRE).
      In the isolates, susceptibility to tigecycline was determined by the standard
      microdilution method. RESULTS: A total of 350 isolates were tested (100 MRSA, 10
      0 VRE, 100 ESBL-positive and 50 AmpC-positive enterobacteria). In the cases of
      VRE and MRSA, no resistance to tigecycline was detected and the minimum
      inhibitory concentrations (MIC) did not exceed 0.25 mg/l and 0.5 mg/l,
      respectively. In ESBL-positive enterobacteria, 97% susceptibility (MIC range = or
      <0.06 to 4 mg/l) was detected; in AmpC-positive enterobacteria, the MIC range was
      = or <0.03-2 mg/l and susceptibility reached 98 %. CONCLUSION: Tigecycline may be
      considered a suitable alternative in the treatment of infections caused by the
      above-mentioned multiresistant strains.

PMID- 19399724
TI  - [Tigecycline: Its position between other antibiotics, features, clinical usage].
AB  - Tigecycline belong to glycylcycline antibiotics. This new group of antibiotics
      was derived from lipophilic tetracyclines but differs from them by higher
      effectivity, lower affinity to bacterial resistance mechanisms, and very long
      half-time. Tigecycline is registered for treatment two groups of infections: skin
      and soft tissue infections and complicated intra-abdominal infections.
      Nevertheless, its therapeutic use probably can be enlarged to pneumonia, STD,
      infections caused by multi-resistant Helicobacter pylori, subacute and chronic
      infections associated with biofilm formation, and serious infections caused by
      intracellular pathogens (serious brucellosis, Q-fever, rickettsial infections).
      By contrast, tigecycline seems not appropriate for treatment sepsis and similar
      acute life-threatening bacterial diseases.

PMID- 19399725
TI  - [Tigecycline for treatment of pneumonia].
AB  - Tigecyclin represents an important contribution for treatment of difficult-to
      treat infections caused by polymicrobial or resistant flora. Its characteristics
      destinate it for use beyond the registered indications. Authors submit two case
      reports documenting its promising effect in patients with complicated pulmonary
      infection in whom standard treatment was not successful.

PMID- 19399726
TI  - [Pharmacokinetics of tetracyclines and glycylcyclines].
AB  - Glycylcyclines were derived from the chemical structure of tetracyclines. After
      they started to be used in clinical practice, tetracycline group came into focus
      as a whole. First-generation tetracyclines feature low lipophilia and they are
      usually available in peroral form only, except rolitetracycline. Moreover, their
      absorption is highly variable and incomplete, ranging usually from 25 % to 60 %
      (absorption of tetracycline ranges from 77 % to 88 %). The majority of first
      generation tetracyclines are not metabolized (though 5 % of tetracycline is
      metabolized to a less active metabolite). Instead, they are most often eliminated
      by renal excretion. Second-generation tetracyclines are 3 to 5 times more
      lipophilic, which enhances their tissue penetration. Doxycycline, the most common
      member of this group, features more than 80 % bioavailability. Bile concentration
      of doxycycline is 10 to 25 times higher as compared with its serum concentration.
      High concentrations of doxycycline are found also in kidneys, liver and bowel.
      Primarily, doxycycline is excreted in bile to feces. Part of doxycycline is
      inactivated in the liver and 40 % of it is excreted by kidneys in urine.
      Tigecycline is administered intravenously and it shows high tissue penetration,
      especially in bones, skin, liver and lungs. Less than 20 % of tigecycline is
      metabolized before it is excreted. Primarily, it is eliminated by biliary/fecal
      excretion in unchanged form. Small part of tigecycline is eliminated as
      metabolites. Secondary routes of elimination are glucuronidation and renal
      excretion.

PMID- 19399727
TI  - [Clostridium difficile as a potential pathogen in preterm neonates].
AB  - OBJECTIVE: To detect the presence of Clostridium difficile toxins A and B in the
      stools of patients hospitalized in the University Hospital Olomouc who developed
      diarrhoea or other abdominal symptoms (abdominal pain, tympanites, indigestion,
      partial intestinal obstruction) related to antibiotic therapy. Given occasional
      dyspepsia and necrotizing enterocolitis in preterm neonates, to consider the
      potential role of these toxins, in addition to that of the immature intestine, in
      the development of the condition. To confirm the hypothesis by stool tests to
      detect the toxins also in normal neonates or those with no gastrointestinal
      symptoms. In selected stool samples, to compare detection of the toxins with C.
      difficile strains confirmed by culture.

PMID- 19399728
TI  - [Foodborne illness caused by bacteria].
AB  - Despite the increasing level of food hygiene in the Czech Republic and other
      European Union member states, agents causing diseases transmitted from animals to
      human remain a serious problem in both human and veterinary medicine of the 21st
      century. The article is concerned with selected bacterial foodborne zoonoses in
      the Czech Republic and EU member states, including antibiotic resistance of the
      pathogens. Some preliminary results on the prevalence of pathogens in the human
      food chain in the Czech region of Moravia in 2007-2008 are presented.

PMID- 19399729
TI  - Konjac glucomannan-based hydrogel with hyaluronic acid as a candidate for a novel
      scaffold for chondrocyte culture.
AB  - Chondrocytes were cultured using konjac glucomannan (KGM) and hyaluronic acid
      (HA) as a scaffold for cartilage regeneration. They were subsequently compared
      with scaffolds produced using agarose hydrogels. Chondrocytes derived from
      Japanese white rabbits were cultured: 2.0 x 10(5) cells were seeded on KGM
      containing hyaluronic acid (KGM/HA) and agarose and cultured for 5 days. Their
      viability was assayed using WST-8 procedures; the ultimate stress and modulus of
      elasticity of each construct was calculated. After 3 days of cultivation, mRNA in
      chondrocytes, such as collagen types I and II and aggrecan, were measured using
      RT-PCR. Both chondrocyte-seeded constructs were stained with safranin O/fast
      green and were evaluated histologically. Chondrocyte viability decreased
      concomitantly with increasing KGM/HA or agarose concentration and with culture
      time. Cell viability in 2% agarose was significantly lower than that in 2% KGM/HA
      on the third and fifth days (p < 0.05). The primary elastic modulus increased
      concomitantly with increasing polysaccharide concentration. Elastic moduli of 2%
      KGM/HA with chondrocytes (0.389 +/- 0.119 N/mm(2)) showed little difference from
      those without chondrocytes (0.283 +/- 0.243 N/mm(2)), although those of 2%
      agarose with chondrocytes (0.403 +/- 0.094 N/mm(2)) were significantly lower than
      those without chondrocytes (0.736 +/- 0.227 N/mm(2); p < 0.05). Collagen type II
      mRNA expression was higher in KGM/HA and agarose than in monolayer cultures,
      although KGM/HA had lower aggrecan mRNA expression levels than did agarose.
      Histological tests of KGM/HA-chondrocyte constructs revealed chondrocyte
      aggregation and proteoglycan production in the pericellular region. The results
      show that KGM/HA might be useful for chondrocyte culture.

PMID- 19399730
TI  - Transmission of human immunodeficiency virus and hepatitis C virus through liver
      transplantation.

PMID- 19399731
TI  - The extent of hepatectomy depends on the preoperative model for end-stage liver
      disease score.

PMID- 19399732
TI  - Improved outcome of adult recipients with a high model for end-stage liver
      disease score and a small-for-size graft.
AB  - Although adult-to-adult living donor liver transplantation (ALDLT) has shown
      comparable outcomes to deceased donor liver transplantation, the outcome of
      patients with a high MELD score (>25) and a small-for-size graft (SFSG<0.8% of
      graft-to-recipient weight ratio) is not known. For 7 years, 167 consecutive
      hepatitis B virus-infected recipients underwent ALDLT at our institution. Based
      on their MELD score without additional score for hepatocellular carcinoma (HCC),
      the recipients were divided into Group L (low MELD score, n = 105) or Group H
      (high MELD score, n = 62). To analyze the risk of the graft size, the patients
      were further stratified as follows: Group Hs (high MELD score and SFSG, n = 11),
      Hn (high MELD score and normal size graft, n = 51), Ls (low MELD score and SFSG,
      n = 18), and Ln (low MELD score and normal size graft, n = 87). The primary
      endpoint was one-year patient survival rate (1-YSR). The mean follow-up period
      was 32.6 months. The mean MELD scores were 17.1 in Group L and 32.6 in Group H.
      Group H had more patients with the complications of cirrhosis but less patients
      with HCC than Group L (p < 0.05). However, major morbidity rates and 1-YSR were
      similar in comparisons between Group L (46.7% and 86.7%) and H (59.7% and 83.8%)
      (p > 0.05). 1-YSR was similar among Group Hs (72.7%), Hn (86.3%), Ls (83.3%), and
      Ln (88.5%) groups (p = 0.278). The multivariate analysis revealed accompanying
      HCC and the year of transplant were risk factors for poor 1-YSR. However, 1-YSR
      without HCC patients was also similar in comparisons between group L (90.2%) and
      H (91.7%) (p = 0.847), and among Group Hs (80.0%), Hn (94.7%), Ls (72.7%), and Ln
      (96.7%) (p = 0.072). In conclusion, high MELD score (>25) didn't predict 1-YSR in
      ALDLT. Improvement of the 1-YSR might be affected by center's experience as well
      as the selection of patients with low risk of recurrence of HCC.

PMID- 19399733
TI  - Transjugular intrahepatic portosystemic shunt to keep vein open.

PMID- 19399734
TI  - Acute kidney injury following liver transplantation: definition and outcome.
AB  - The incidence of acute kidney injury (AKI) has been reported to vary between 17%
      and 95% post-orthotopic liver transplantation. This variability may be related to
      the absence of a uniform definition of AKI in this setting. The purpose of this
      study was to identify the degree of AKI that is associated with long-term adverse
      outcome. Furthermore, to determine the best definition (for use in future
      studies) of AKI not requiring dialysis in post-liver transplant patients, we
      retrospectively reviewed the effect of 3 definitions of AKI post-orthotopic liver
      transplantation on renal and patient outcome between 1997 and 2005. We compared
      patients with AKI to a control group without AKI by each definition. AKI was
      defined in 3 groups as an acute rise in serum creatinine, from the pretransplant
      baseline, of >0.5 mg/dL, >1.0 mg/dL, or >50% above baseline to a value above 2
      mg/dL. In all groups, the glomerular filtration rate was significantly lower at
      both 1 and 2 years post-transplant. Patient survival was worse in all groups.
      Graft survival was worse in all groups. The incidence of AKI was highest in the
      group with a rise in creatinine of >0.5 mg/dL (78%) and lowest in patients with a
      rise in creatinine of >50% above 2.0 mg/dL (14%). Even mild AKI, defined as a
      rise in serum creatinine of >0.5 mg/dL, was associated with reduced patient and
      graft survival. However, in comparison with the other definitions, the definition
      of AKI with the greatest impact on patient's outcome post-liver transplant was a
      rise in serum creatinine of >50% above baseline to >2 mg/dL.

PMID- 19399735
TI  - A single-center experience of 500 liver transplants using the modified piggyback
      technique by Belghiti.
AB  - Over the past 4 decades, the surgical techniques of liver transplantation (LTx)
      have permanently evolved and been modified. Among these, the modified piggyback
      (MPB) technique by Belghiti offers specific advantages. The objective of this
      study was to present our single-center experience with the MPB technique in 500
      cases. Recipients' perioperative data were prospectively collected and evaluated.
      Postoperative and specific complications, stay in the intensive and intermediate
      care unit, and the mortality rate with cause of death were analyzed. Most
      recipients were classified as Child C (49.1%). For the patients who underwent LTx
      for the first time, alcoholic (23.9%) and viral (22.2%) cirrhosis and
      hepatocellular carcinoma (15.1%) were the prevalent indications. The overall
      median warm ischemia time, anastomosis duration, and operative time were 45, 108,
      and 320 minutes, respectively. The median intraoperative blood loss was 1500 mL.
      A venovenous bypass was never needed to maintain hemodynamic stability. Only in a
      few cases was temporary inferior vena cava clamping necessary. Most prominent
      surgical complications were hemorrhage, hematoma, and wound dehiscence. Renal
      failure occurred in 6.2% of patients. The overall median stay in the intensive
      and intermediate care unit was 14 days. The mortality rates within 30 and 90 days
      were 6.3% and 13.3%, respectively. No technique-related death occurred. The MPB
      technique by Belghiti is a feasible and simple LTx technique. The caval flow is
      preserved during the anhepatic phase, and this minimizes the need for venovenous
      bypass or portocaval shunt. This technique requires only 1 caval anastomosis,
      which is easy to perform with a short anhepatic phase. To minimize the risk of
      outflow obstruction, attention should be paid by doing a wide cavocavostomy
      cranially to the donor inferior vena cava in a door-lock manner. This technique
      can be applied in almost all patients undergoing LTx for the first time and liver
      retransplantation as well.

PMID- 19399736
TI  - Postreperfusion syndrome during liver transplantation for cirrhosis: outcome and
      predictors.
AB  - During orthotopic liver transplantation (OLT), a marked decrease in blood
      pressure following unclamping of the portal vein and liver reperfusion is
      frequently observed and is termed postreperfusion syndrome (PRS). The predictive
      factors and clinical consequences of PRS are not fully understood. The goal of
      this study was to identify predictors of PRS and morbidity/mortality associated
      with its occurrence during OLT in patients with cirrhosis. During a 3-year
      period, all consecutive OLT procedures performed in patients with cirrhosis were
      studied. Exclusion criteria were OLT for acute liver failure, early
      retransplantation, combined liver/kidney transplantation, and living-donor
      related transplantation. PRS was defined as a decrease in the mean arterial
      pressure of more than 30% of the value observed in the anhepatic stage, for more
      than 1 minute during the first 5 minutes after reperfusion of the graft.
      Transplantation was performed with preservation of the inferior vena cava with or
      without temporary portocaval shunt. Associations between PRS and donor and
      recipient demographic data, recipient operative and postoperative outcomes were
      tested with bivariate statistics. Independent predictors of PRS were determined
      in multivariable logistic regression analysis. Of the 75 patients included in the
      study, 20 patients (25%) developed PRS. In a multivariable analysis, absence of a
      portocaval shunt [odds ratio (95% confidence interval) = 4.42 (1.18-17.6)] and
      duration of cold ischemia [odds ratio (95% confidence interval) = 1.34 (1.07
      1.72)] were independent predictors of PRS. Patients who experienced PRS displayed
      more postoperative renal failure and lower early (<15 days after OLT) survival
      (80% versus 96%; P = 0.04). In conclusion, the absence of portocaval shunt and
      the duration of cold ischemia were independent predictors of intraoperative PRS.
      PRS was associated with significant adverse postoperative outcome. These results
      provide realistic clinical targets to improve patient outcome after OLT for
      cirrhosis.

PMID- 19399737
TI  - Small size and disease severity in living donation: a difficult match.

PMID- 19399738
TI  - What's in a name, AKI?

PMID- 19399740
TI  - Biliary obstruction as a complication of transjugular intrahepatic portosystemic
      shunt.

PMID- 19399742
TI  - Safety and effectiveness of ezetimibe in liver transplant recipients with
      hypercholesterolemia.
AB  - Hypercholesterolemia is a common problem among transplant recipients. Despite
      package-insert warnings about the potential side effects of the use of statins in
      patients with chronic liver disease, they are often prescribed for liver
      transplant recipients. Unlike statins, ezetimibe acts through inhibition of
      enterohepatic recirculation of lipids. We report the effectiveness and safety of
      ezetimibe among liver transplant recipients because this has been evaluated
      previously only in kidney and heart transplant patients. A consecutive cohort of
      25 liver graft recipients with serum low-density lipoprotein (LDL) levels > 100
      mg/dL (2.5 mmol/L) after a mean (+/-standard deviation) of 55 +/- 21 months
      following liver transplantation received ezetimibe (10 mg orally every day) for
      at least 6 months. Serum lipid profiles, liver and renal function tests, and
      dosages and blood levels of the immunosuppression drugs at baseline, 3 months,
      and 6 months were prospectively collected. The overall mean age was 58 +/- 12
      years, and 56% were males. Statin therapy and fibrates were already being used in
      32% and 20% of recipients for elevated LDL and/or triglycerides, respectively.
      The immunosuppression regimen included cyclosporine in 48% of subjects,
      tacrolimus in 32%, sirolimus in 48%, and mycophenolate mofetil in 44%; only 12%
      were on oral prednisone with a maximum daily dose of 5 mg. After ezetimibe was
      started, an 18% reduction in LDL values was observed [at baseline, 147 +/- 35
      mg/dL (3.8 +/- 0.9 mmol/L), and at 6 months, 120 +/- 31 mg/dL (3.1 +/- 0.8
      mmol/L); P = 0.010]. After 6 months, an additional 32% achieved the target LDL
      level of <100 mg/dL. None of the remaining variables, including immunosuppression
      drug levels, varied significantly during ezetimibe therapy. None of the subjects
      required adjustments in their pharmacological dosages. One discontinued ezetimibe
      3 months later because of cost, 2 subjects had minimal nausea, 1 subject had
      myalgias without a rise in creatine phosphokinase, and 1 subject had a transient
      elevation (3-5 times) in liver enzymes from baseline with increases in the total
      and indirect bilirubin levels. In conclusion, among liver transplant recipients,
      hypercholesterolemia can be effectively treated with ezetimibe with few side
      effects and no interaction with immunosuppressive regimens.

PMID- 19399741
TI  - Gene expression profiling of acute cellular rejection in rat liver
      transplantation using DNA microarrays.
AB  - Acute cellular rejection (ACR) is still a major problem in organ transplantation,
      and its genetic and molecular mechanisms remain poorly understood. We used DNA
      microarrays to investigate the gene expression profiles in ACR. We hypothesized
      that changes of gene expression in grafts could also be detected in peripheral
      blood leukocytes. We first compared the gene expression profiles in liver
      isografts (Lewis to Lewis) and allografts (Dark Agouti to Lewis) harvested from
      rats at days 1, 3, 5, and 7 after transplantation. Hierarchical clustering
      analysis indicated that gene expression started to change on day 3, and 89
      differentially expressed genes were extracted from allografts in comparison with
      isografts at day 3. Most of the up-regulated genes were associated with graft
      infiltrating leukocytes. We then confirmed the similarity of gene expression
      changes in peripheral leukocytes by quantitative real-time polymerase chain
      reaction. We also investigated the gene expression changes in other inflammatory
      and liver dysfunction models. Two interferon-gamma inducible genes, interferon
      regulatory factor 1 and guanylate nucleotide binding protein 2, were
      overexpressed in both the peripheral leukocytes and liver graft during ACR.
      Although further studies are necessary, these 2 genes in peripheral leukocytes
      could be potentially useful markers for rejection or immunosuppression.

PMID- 19399743
TI  - Successful liver transplantation for Budd-Chiari syndrome in a patient with
      paroxysmal nocturnal hemoglobinuria treated with the anti-complement antibody
      eculizumab.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hemolytic anemia
      caused by somatic mutations in the phosphatidylinositol glycan-complementation
      class A gene and the resulting absence of a key complement regulatory protein,
      CD59. Affected red blood cells in patients with PNH undergo intravascular
      complement-mediated lysis with resulting anemia, hemoglobinuria, and venous
      thromboses. Hepatic venous outflow thrombosis [Budd-Chiari syndrome (BCS)] is
      especially common in PNH patients and often fatal. The few case reports of
      outcomes in patients undergoing liver transplant for BCS secondary to PNH detail
      instances of recurrent BCS as well as early thrombotic portal vein occlusion and
      hepatic artery thrombosis requiring retransplantation. PNH is therefore generally
      considered a contraindication to liver transplantation. Here we present the first
      report of a patient with PNH and BCS undergoing successful liver transplantation
      while receiving eculizumab, a humanized monoclonal antibody that blocks the
      activation of the terminal complement at C5.

PMID- 19399744
TI  - The therapeutic potential of human umbilical mesenchymal stem cells from
      Wharton's jelly in the treatment of rat liver fibrosis.
AB  - We investigated the effect of human umbilical mesenchymal stem cells (HUMSCs)
      from Wharton's jelly on carbon tetrachloride (CCl4)-induced liver fibrosis in
      rats. Rats were treated with CCl4 for 4 weeks, and this was followed by a direct
      injection of HUMSCs into their livers. After 4 more weeks of CCl4 treatment (8
      weeks in all), rats with HUMSC transplants [CCl4 (8W)+HUMSC liver] exhibited a
      significant reduction in liver fibrosis, as evidenced by Sirius red staining and
      a collagen content assay, in comparison with rats treated with CCl4 for 8 weeks
      without HUMSC transplants [CCl4 (8W)]. Moreover, rats in the CCl4 (8W)+HUMSC
      (liver) group had significantly lower levels of serum glutamic oxaloacetic
      transaminase, glutamic pyruvate transaminase, alpha-smooth muscle actin, and
      transforming growth factor-beta1 in the liver, whereas the expression of hepatic
      mesenchymal epithelial transition factor-phosphorylated type (Met-P) and
      hepatocyte growth factor was up-regulated, in comparison with the CCl4 (8W)
      group. Notably, engrafted HUMSCs scattered mostly in the hepatic connective
      tissue but did not differentiate into hepatocytes expressing human albumin or
      alpha-fetoprotein. Instead, these engrafted, undifferentiated HUMSCs secreted a
      variety of bioactive cytokines that may restore liver function and promote
      regeneration. Human cytokine assay revealed that the amounts of human cutaneous T
      cell-attracting chemokine, leukemia inhibitory factor, and prolactin were
      substantially greater in the livers of the CCl4 (8W)+HUMSC (liver) group, with
      considerably reduced hepatic inflammation manifested by a micro positron emission
      tomography scan. Our findings suggest that xenogeneic transplantation of HUMSCs
      is a novel approach for treating liver fibrosis and may be a promising
      therapeutic intervention in the future.

PMID- 19399745
TI  - Designated liver transplant anesthesia team reduces blood transfusion, need for
      mechanical ventilation, and duration of intensive care.

PMID- 19399746
TI  - Follow-up of Chinese liver transplant recipients in Hong Kong.
AB  - The outcome of liver transplantation in China remains speculative. From 1998 to
      2007, 177 adult Hong Kong patients underwent liver transplantation in China and
      were subsequently followed up at Queen Mary Hospital, Hong Kong. One hundred six
      (59.9%) patients had hepatocellular carcinoma (HCC). The grafts were probably
      derived from uncontrolled non-heart-beating donors. The 1-month mortality rate
      was 4.0%. The 1-, 3-, and 5-year overall survival rates were 73.9%, 59.0%, and
      53.9%, respectively. The 5-year overall survival rates for non-HCC, HCC, HCC
      (within the Milan criteria), and HCC (beyond the Milan criteria) patients were
      66.3%, 44%, 58%, and 26.2%, respectively. The long-term survival was compromised
      by the high incidence of HCC recurrence and graft failure secondary to diffuse
      intrahepatic biliary strictures. The overall survival rate of the entire group
      was lower than that of the patients receiving deceased donor liver grafts at
      Queen Mary Hospital in the same period. For non-HCC patients, however, the 5-year
      survival rate of 66.3% was comparable to that of recent reports from the Western
      world.

PMID- 19399747
TI  - Risk factors for developing de novo autoimmune hepatitis associated with anti
      glutathione S-transferase T1 antibodies after liver transplantation.
AB  - De novo autoimmune hepatitis (de novo AIH) is a rare form of graft dysfunction
      that develops after liver transplantation (LT) in patients transplanted for
      conditions other than autoimmune disorders. Although characterized by
      biochemical, serological, and histological features of AIH, de novo AIH is
      sometimes associated with atypical serum autoantibodies, many of which are
      directed against glutathione S-transferase T1 (anti-GSTT1). GSTT1 donor/recipient
      genotype mismatch has been suggested as a necessary condition for the appearance
      of autoantibodies and de novo AIH. However, clinically evident disease is not
      observed in all patients with anti-GSTT1 antibodies. We examined the incidence of
      de novo AIH and its conditioning (risk) factors in patients with anti-GSTT1
      antibodies. Anti-GSTT1 autoantibodies were detected in 29 of 419 [6.9%; 95%
      confidence interval (CI), 4.9-9.8] consecutive adult LT recipients with
      donor/recipient GSTT1 mismatch. Twenty of 27 assessable patients (74%) developed
      de novo AIH after a median follow-up of 26 months (95% CI, 19.2-32.8). The
      probability of de novo AIH was 11%, 44%, and 60% 12, 24, and 36 months after LT,
      respectively. No relationship emerged between de novo AIH and recipient gender,
      donor and recipient age, rejection episodes, immunosuppressive regime, allelic
      GSTT1 expression, human leukocyte antigen distribution, or cytomegalovirus
      infection. Multivariate analysis identified male donor [hazard ratio (HR), 3.3;
      95% CI, 1.18-9.26; P = 0.018], nonalcoholic etiology (HR, 4.67; 95% CI, 1.64
      13.3; P = 0.002), and high anti-GSTT1 titer (HR, 2.98; 95% CI, 1.04-8.57; P =
      0.035) as independent predictors of de novo AIH. Most patients with anti-GSTT1
      antibodies and donor/recipient GSTT1 mismatch developed clinically evident de
      novo AIH after LT. The risk of developing the disease was increased by male donor
      gender, nonalcoholic etiology of original liver disease, and a high anti-GSTT1
      titer.

PMID- 19399748
TI  - Review of major adverse effects of androgen-deprivation therapy in men with
      prostate cancer.
AB  - Androgen-deprivation therapy (ADT) is a common treatment for men with prostate
      cancer. Although ADT is effective at suppressing prostate-specific antigen (PSA),
      stabilizing disease, alleviating symptoms in advanced disease, and potentially
      prolonging survival, it is not without serious side effects. However, to the
      authors' knowledge, there is lack of a systematic review of its major adverse
      effects to date. The authors of this report systematically reviewed and
      quantitatively assessed the literature on skeletal and cardiac side effects
      associated with ADT in men with prostate cancer. The PubMed database was searched
      for relevant published articles from 1966 to May 2008, and 683 articles were
      reviewed systematically from an original 20 different Medical Subject Heading
      search combinations. The focus of the review was on bone-related and
      cardiovascular-related outcomes. When appropriate, results were pooled from
      articles on specific adverse outcomes, summary risk estimates were calculated,
      and tests of heterogeneity were performed. Fourteen articles were identified that
      met inclusion criteria from the original 683 studies. Men who underwent ADT for
      prostate cancer had a significantly increased risk of overall fracture of 23%
      (summary relative risk, 1.23; 95% confidence interval [95% CI], 1.10-1.38)
      compared with men who had prostate cancer but who did not undergo ADT.
      Furthermore, men who underwent ADT had a 17% increase in cardiovascular-related
      mortality compared with men who did not undergo with ADT (summary hazards ratio,
      1.17; 95% CI, 1.07-1.29). Significant elevations in the risk of diabetes also
      were observed from 2 large studies. ADT was associated with an increased risk of
      skeletal fracture, incident diabetes, and cardiovascular-related mortality,
      although the absolute risk of these events was low. Preventive measures against
      these adverse effects and careful assessment of patient's baseline health status
      should be considered.

PMID- 19399749
TI  - The prostatic environment suppresses growth of androgen-independent prostate
      cancer xenografts: an effect influenced by testosterone.
AB  - BACKGROUND: Interactions between prostate cancer cells and their surrounding
      stroma play an important role in the growth and maintenance of prostate tumors.
      To elucidate this further, we investigated how growth of androgen-dependent (AD)
      LNCaP and androgen-independent (AI) LNCaP-19 prostate tumors was affected by
      different microenvironments and androgen levels. METHODS: Tumor cells were
      implanted subcutaneously and orthotopically in intact and castrated
      immunodeficient mice. Orthotopic tumor growth was followed by magnetic resonance
      imaging (MRI). Gene expression in the tumors was evaluated by means of microarray
      analysis and microvessel density (MVD) was analyzed using immunohistochemistry.
      RESULTS: The results showed that LNCaP-19 tumors grew more rapidly at the
      subcutaneous site than in the prostate, where tumors were obviously inhibited.
      Castration of the mice did not affect ectopic tumors but did result in increased
      tumor growth in the prostatic environment. This effect was reversed by
      testosterone treatment. In contrast to LNCaP-19, the LNCaP cells grew rapidly in
      the prostate and castration reduced tumor development. Gene expression analysis
      of LNCaP-19 tumors revealed an upregulation of genes, inhibiting tumor growth
      (including ADAMTS1, RGS2 and protocadherin 20) and a downregulation of genes,
      promoting cell adhesion and metastasis (including N-cadherin and NRCAM) in the
      slow-growing orthotopic tumors from intact mice. CONCLUSIONS: The results show
      that the prostatic environment has a varying impact on AD and AI tumor
      xenografts. Data indicate that the androgen-stimulated prostatic environment
      limits growth of orthotopic AI tumors through induction of genes that inhibit
      tumor growth and suppression of genes that promote cell adhesion and metastasis.

PMID- 19399750
TI  - Sequence dependence of cell growth inhibition by EGFR-tyrosine kinase inhibitor
      ZD1839, docetaxel, and cisplatin in head and neck cancer.
AB  - BACKGROUND: This study was to explore whether the efficacy of the epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Z, Iressa,
      gefitinib) plus chemotherapeutic agents docetaxel (D) and cisplatin (P) may
      benefit from sequencing of the combination. METHODS: Three head and neck cancer
      cell lines were used to study the effect of various combinations of and relative
      sequencing of D, P, and Z in cell growth inhibition. A population pharmacokinetic
      stimulation study was conducted on Z in silico and used together with the growth
      inhibition data to derive principles for future in vivo use of this drug
      combination. RESULTS: The inhibitory effects of Z on combinations of D and P were
      sequence dependent. Treatment simultaneously with DPZ or with DP followed by Z
      (DP-->Z) showed synergistic effects in all 3 cell lines. However, sequencing with
      Z followed by DP (Z-->DP), gave an antagonistic effect, suggesting that D and P
      should be administered when the effect of Z is low. The induction of apoptosis
      was also sequence dependent. The in silico pharmacokinetic study suggested the
      feasibility of deriving a 5-day-on/2-day-off regimen for Z, in which D and P
      administration commences when levels of Z are low, allowing levels of Z to
      accumulate sufficiently during the remainder of the cycle. CONCLUSION: These data
      suggests that it is feasible to design clinical trials with these settings to
      maximize the efficacy of this combined drug regimen.

PMID- 19399751
TI  - Accessory nerve function after level 2b-preserving selective neck dissection.
AB  - BACKGROUND: The aim of this prospective study was to evaluate the relationship
      between accessory nerve functions and level 2b-preserving selective neck
      dissection. METHODS: Forty-one necks of 30 patients with laryngeal cancer who
      underwent unilateral or bilateral level 2b-preserving neck dissections, between
      February 2003 and July 2005, were evaluated. Neck and shoulder movements and
      muscle strengths were examined and electroneuromyography (ENMG) was performed
      preoperatively at the postoperative 21st day and 6th month. Pathological
      anatomical findings at the postoperative 6th month were also evaluated. RESULTS:
      All shoulder movements and muscle strengths were preserved. Neck extension,
      rotation movements, and flexion strengths were restricted. ENMG values were
      affected moderately in the early postoperative period and improved slightly in
      the late postoperative period. None of the patients developed shoulder syndrome
      or adhesive capsulitis. CONCLUSION: Preserving level 2b during selective neck
      dissection decreases trauma to the accessory nerve and improves functional
      results.

PMID- 19399752
TI  - Operating on commission: analyzing how physician financial incentives affect
      surgery rates.
AB  - This paper employs a nationally representative, household-based dataset in order
      to test how the compensation method of both the specialists and the primary care
      providers affects surgery rates. After controlling for adverse selection, I find
      that when specialists are paid through a fee-for-system scheme rather than on a
      capitation basis, surgery rates increase 78%. The impact of primary care
      physician compensation on surgery rates depends on whether or not referral
      restrictions are present.

PMID- 19399753
TI  - Optimal clinical trial design using value of information methods with imperfect
      implementation.
AB  - Traditional sample size calculations for randomized clinical trials are based on
      the tests of hypotheses and depend on somewhat arbitrarily chosen factors, such
      as type I and II errors rates and the smallest clinically important difference.
      In response to this, many authors have proposed the use of methods based on the
      value of information as an alternative. Previous attempts have assumed perfect
      implementation, i.e. if current evidence favors the new intervention and no new
      information is sought or expected, all future patients will receive it. A
      framework is proposed to allow for this assumption to be relaxed. The profound
      effect that this can have on the optimal sample size and expected net gain is
      illustrated on two recent examples. In addition, a model for assessing the value
      of implementation strategies is proposed and illustrated.

PMID- 19399754
TI  - The nuchal translucency and the fetal heart: a literature review.
AB  - In this overview the current knowledge of the relationship between an increased
      nuchal translucency (NT) measurement and fetal heart structure and function in
      chromosomally normal fetuses is reviewed. Relevant pathophysiological theories
      behind the increased NT are discussed. Fetuses with an increased NT have an
      increased risk for congenital heart disease (CHD) with no particular bias for one
      form of CHD over another. This risk increases with increasing NT measurement.
      Although the NT measurement is only a modestly effective screening tool for all
      CHD when used alone, it may indeed be effective in identifying specific CHD
      "likely to benefit" from prenatal diagnosis. The combination of an increased NT,
      tricuspid regurgitation and an abnormal ductus venosus (DV) Doppler flow profile,
      is a strong marker for CHD. A fetal echocardiogram should be performed at 20
      weeks' gestation in fetuses with an NT > or = 95th percentile but < 99th
      percentile. When the NT measurement is > or = 99th percentile, or when tricuspid
      regurgitation and/or an abnormal DV flow pattern is found along with the
      increased NT, an earlier echocardiogram is indicated, followed by a repeat scan
      at around 20 weeks' gestation. The resultant increased demand for early fetal
      echocardiography and sonographers with this special expertise needs to be planned
      and provided for.

PMID- 19399755
TI  - Fetal karyotype in feto-fetal transfusion syndrome: a 7-year experience.

PMID- 19399756
TI  - Prenatal diagnosis of achondroplasia: new specific signs.
AB  - BACKGROUND: Achondroplasia is one of the most common forms of short limb
      dwarfism. It is usually suspected on third trimester routine ultrasound because
      of very shortened long bones. We have described two new prenatal sonographic
      signs of achondroplasia visible at the proximal femoral metaphysis. METHODS: Over
      5 years, five fetuses were diagnosed with achondroplasia at the Grenoble Prenatal
      Diagnosis Centre. Ultrasound and tomographic examinations were performed by
      specialists. To study the proximal metaphysis, the ultrasound transducer was
      positioned at a 45 degree angle to the diaphyseal axis. Postnatal diagnosis was
      confirmed. RESULTS: On computed tomography and postnatal X-ray, proximal femoral
      metaphysis appeared rounded, with poor, uneven ossification. Connexion to
      diaphysis was abnormal, with relative overgrowth of the periosteum, creating a
      new diagnostic sign that we called the 'collar hoop' sign. On ultrasound, all
      fetuses had a very rounded metaphyseal-epiphyseal interface, with an angle
      connexion to diaphysis wider than expected. The 'collar hoop' sign was obvious on
      four of the fetuses. During the same period, proximal femoral metaphyses appeared
      normal in 653 healthy fetuses, suggesting high specificity of those two new
      signs. CONCLUSION: Metaphysis examination is recommended if fetal femur length
      measures below the fifth percentile, as normal aspect may rule out
      achondroplasia.

PMID- 19399757
TI  - Reference values for gamma-glutamyl-transferase in amniotic fluid in normal
      pregnancies.
AB  - OBJECTIVE: Nonvisualization of the fetal gallbladder by ultrasound poses a
      diagnostic dilemma. The aim of the study was to establish reference values for
      the hepatobiliary enzyme gamma-glutamyl-transferase (GGT) in amniotic fluid in
      normal pregnancies, and to determine the maximal week of gestation in which
      reference values can be determined. METHOD: A cross-sectional design was used.
      The study group consisted of pregnant women at 16 gestational weeks or more
      referred to our ultrasound unit for amniocentesis. Amniotic fluid was assayed for
      levels of GGT and other hepatobiliary enzymes using the Integra 800 device. The
      5th and 95th percentiles for each gestational week were calculated. RESULTS: A
      total of 263 samples were analyzed. After conversion to log units, enzyme levels
      showed a good correlation with gestational week (Pearson). The mean values and
      the 5th and 95th percentiles were calculated for gestational weeks 16 to 22.
      Beyond 22 weeks, the number of examinations was insufficient for analysis. On
      multiple regression analysis, log values of alkaline phosphatase, maternal age,
      and gestational age independently affected log GGT values. Levels of alkaline
      phosphatase, aspartate aminotransferase, and alanine aminotransferase were too
      low, and their correlation with gestational week too poor for calculation of
      reference values. CONCLUSION: GGT reference values in amniotic fluid in normal
      pregnancies were defined for gestational weeks 16 to 22. These data may be useful
      for differentiating isolated absence of fetal gallbladder from extrahepatic
      biliary atresia.

PMID- 19399758
TI  - Determination of tryptophan in bee pollen and royal jelly by high-performance
      liquid chromatography with fluorescence detection.
AB  - A method for tryptophan analysis in bee pollen and royal jelly was developed
      using HPLC with fluorescence detection. To determine the free tryptophan in bee
      pollen and royal jelly, ultrasonic extraction was performed using water (pH 6.3)
      acetonitrile (10:1, v/v) as extraction solvent. While determining the total
      tryptophan in these bee products, the method involves alkaline hydrolysis of the
      proteins with 4 mol/L sodium hydroxide at 110 degrees C for 20 h under anaerobic
      conditions. The operating conditions for the HPLC analysis were: Symmetry C(18)
      column (4.6 x 250 mm, 5 microm), 0.1% trifluoroacetic acid-methanol (75:25, v/v)
      as the mobile phase at a flow rate of 1.0 mL/min at 30 degrees C. The
      fluorescence detector was operated at an excitation wavelength of 280 nm and an
      emission wavelength of 340 nm. A linear response (r(2 )> 0.9998) was obtained in
      the range 0.0625-5.0 microg/mL. The method was successfully applied to the
      determination of the free and total tryptophan contents in bee pollens, which
      were 0.069 +/- 0.003 and 2.693 +/- 0.476 mg/g, respectively, while only the total
      tryptophan was detected in royal jelly, with a content of 1.743 +/- 0.066 mg/g.

PMID- 19399759
TI  - Enhanced transgene expression in the mouse skeletal muscle infected by the adeno
      associated viral vector with the human elongation factor 1alpha promoter and a
      human chromatin insulator.
AB  - BACKGROUND: Efficient and continuous expression of a therapeutic transgene is a
      key factor for improving the efficacy of gene therapy. Some insulators are known
      to contribute to continuous high-level expression of a therapeutic transgene.
      METHODS: Using the human AAVS1 insulator (DHS) found in the AAVS1 DNase I
      hypersensitive site, chicken beta-globin insulator (cHS4) and sea urchin
      arylsufatase insulator (Ars), we newly constructed three recombinant adeno
      associated virus vectors (rAAV) and examined their capability of transducing the
      mouse quadriceps muscle. RESULTS: DHS increased transgene expression from the
      human elongation factor 1alpha promoter (EF) by 1000-fold, up to the high level
      achieved by the human cytomegalovirus immediate early promoter/enhancer (CMV),
      which comprises an extremely strong promoter for driving a transgene. cHS4
      enhanced the expression by 100-fold, whereas Ars did not. The enhanced expression
      was maintained for at least 24 weeks. Vector copy numbers were similar with and
      without DHS or cHS4; thus, the enhancement is most likely due to up-regulated
      transcription. Neither DHS, nor cHS4 affected transgene expression from CMV. DHS
      enhanced expression from the human muscle creatine kinase promoter/enhancer by
      100-fold in mice, as did DHS from EF. CONCLUSIONS: Although DHS was unable to
      further enhance high expression from the strong viral enhancer/promoter, it
      enhanced low expression from the human promoters by 100- to 1000-fold. Thus, DHS
      may be useful for constructing rAAVs that express a therapeutic transgene from
      less efficient, tissue specific promoters.

PMID- 19399760
TI  - Geometric similarity between protein-RNA interfaces.
AB  - A new method is described to measure the geometric similarity between protein-RNA
      interfaces quantitatively. The method is based on a procedure that dissects the
      interface geometry in terms of the spatial relationships between individual amino
      acid nucleotide pairs. Using this technique, we performed an all-on-all
      comparison of 586 protein-RNA interfaces deposited in the current Protein Data
      Bank, as the result, an interface-interface similarity score matrix was obtained.
      Based upon this matrix, hierarchical clustering was carried out which yielded a
      complete clustering tree for the 586 protein-RNA interfaces. By investigating the
      organizing behavior of the clustering tree and the SCOP classification of protein
      partners in complexes, a geometrically nonredundant, diverse data set
      (representative data set) consisting of 45 distinct protein-RNA interfaces was
      extracted for the purpose of studying protein-RNA interactions, RNA regulations,
      and drug design. We classified protein-RNA interfaces into three types. In type
      I, the families and interface structural classes of the protein partners, as well
      as the interface geometries are all similar. In type II, the interface geometries
      and the interface structural classes are similar, whereas the protein families
      are different. In type III, only the interface geometries are similar but the
      protein families and the interface structural classes are distinct. Furthermore,
      we also show two new RNA recognition themes derived from the representative data
      set.

PMID- 19399761
TI  - Evaluation of the searching abilities of HBOP and HBSITE for binding pocket
      detection.
AB  - We evaluated the pocket-searching abilities of the computer programs HBOP and
      HBSITE, in which hydrophobic potentials calculated on grid points generated
      around a protein function as an indicator of the pocket-like property-using a
      test set of 458 experimentally observed structures of protein-ligand complexes.
      The results were compared with those obtained using the alternative algorithms
      PASS and SiteID, which only consider geometric properties, and Q-SiteFinder,
      which considers not only geometry but also physicochemical properties. The
      comparison revealed that HBOP and HBSITE could detect experimentally observed
      ligand-binding pockets for more test complexes than PASS and SiteID. In addition,
      the success rate of HBOP for detecting binding pockets was higher than that of Q
      SiteFinder, and that of HBSITE was comparable with that of Q-SiteFinder. Results
      of tests for ligand-unbound state proteins indicated that HBSITE was more
      appropriate than Q-SiteFinder for pocket searches of ligand-unbound proteins, and
      HBSITE was more robust than Q-SiteFinder against structural differences between
      ligand-bound and -unbound state proteins.

PMID- 19399762
TI  - Precise and fast secondary ion mass spectrometry depth profiling of polymer
      materials with large Ar cluster ion beams.
AB  - We demonstrate depth profiling of polymer materials by using large argon (Ar)
      cluster ion beams. In general, depth profiling with secondary ion mass
      spectrometry (SIMS) presents serious problems in organic materials, because the
      primary keV atomic ion beams often damage them and the molecular ion yields
      decrease with increasing incident ion fluence. Recently, we have found reduced
      damage of organic materials during sputtering with large gas cluster ions, and
      reported on the unique secondary ion emission of organic materials. Secondary
      ions from the polymer films were measured with a linear type time-of-flight (TOF)
      technique; the films were also etched with large Ar cluster ion beams. The mean
      cluster size of the primary ion beams was Ar(700) and incident energy was 5.5
      keV. Although the primary ion fluence exceeded the static SIMS limit, the
      molecular ion intensities from the polymer films remained constant, indicating
      that irradiation with large Ar cluster ion beams rarely leads to damage
      accumulation on the surface of the films, and this characteristic is excellently
      suitable for SIMS depth profiling of organic materials.

PMID- 19399763
TI  - Structural studies on Helicobacter pylori 3-deoxy-D-manno-2-octulosonate-8
      phosphate synthase using electrospray ionization mass spectrometry: a tetrameric
      complex composed of dimeric dimers.
AB  - Helicobacter pylori 3-deoxy-D-manno-2-octulosonate-8-phosphate (KDO8P) synthase
      catalyzes the conversion of D-arabinose-5-phosphate (A5P) and phosphoenolpyruvate
      (PEP) to produce KDO8P and inorganic phosphate. Since this protein is absent in
      mammals, it might therefore be an attractive target for the development of new
      antibiotics. Unlike E. coli KDO8P synthase (class I), the H. pylori counterpart
      is a class II enzyme, where it requires a divalent transition metal ion for
      catalysis. Although the metal ions have been shown to be important for catalysis,
      their role in the structure is not understood. Using electrospray ionization mass
      spectrometry (ESI-MS), the role of the metal ions in H. pylori KDO8P synthase has
      been investigated. This protein is found to be a tetramer in the gas phase but
      dissociates into the dimer with increasing declustering potential (DP2)
      suggesting an existence of a 'structurally specific' tetramer. An examination of
      mass spectra revealed that the tetrameric state of the Cd(2+)-reconstituted
      enzyme is less stable than those of the Zn(2+)-, Co(2+)- and Cu(2+)-enzymes. The
      stoichiometry of metal binding to the protein depends on the nature of the metal
      ion. Taken together, our data suggest that divalent metal ions play an important
      role in the quaternary structure of the protein and the tetrameric state may be
      primarily responsible for catalysis. This study demonstrates the first structural
      characterization and stoichiometry of metal binding in class II KDO8P synthase
      using electrospray ionization quadrupole time-of-flight mass spectrometry under
      nondenaturing conditions.

PMID- 19399764
TI  - Positive mode electrospray tandem mass spectrometry of poly(methacrylic acid)
      oligomers.
AB  - The dissociation of small poly(methacrylic acid) (PMAA) cations produced by
      electrospray was characterized by tandem mass spectrometry. Similarly to PMAA
      ions produced in the negative ion mode, the two electrosprayed cationic forms,
      namely [PMAA+Na](+) and [PMAA-H+2Na](+), were shown to fragment via a major
      pathway consisting of successive dehydration steps. Elimination of a water
      molecule would occur between two consecutive acid groups in a charged-remote
      mechanism and was shown to proceed as many times as pairs of acidic pendant
      groups were available. As a result, comparing the number of dehydration steps
      observed in the MS/MS spectrum of two consecutive oligomers from the polymeric
      distribution reveals the degree of polymerization of the molecule. Secondary less
      informative reactions were shown to consist of losses of CO and/or CO(2),
      depending on the nature of the precursor ion. These fragmentation rules could be
      used to characterize PMAA-based copolymers, as successfully demonstrated for a
      polymeric impurity in the tested PMAA sample.

PMID- 19399765
TI  - A high-throughput bioanalytical platform using automated infusion for tandem mass
      spectrometric method optimization and its application in a metabolic stability
      screen.
AB  - Liquid chromatography/tandem mass spectrometry (LC/MS/MS) is the bioanalytical
      method of choice to support plate-based, in vitro early ADME (Absorption,
      Distribution, Metabolism and Excretion) screens such as metabolic stability
      (Metstab) assessment. MS/MS method optimization has historically been the
      bottleneck in this environment, where samples from thousands of discrete
      compounds are analyzed on a monthly basis, mainly due to the lack of a high
      quality commercially available platform to handle the necessary MS/MS method
      optimization steps for sample analysis by selected reaction monitoring (SRM) on
      triple quadrupole mass spectrometers. To address this challenge, we recently
      developed a highly automated bioanalytical platform by successfully integrating
      QuickQuan 2.0, a unique high-throughput solution featuring MS/MS method
      optimization by automated infusion, with a customized in-house software tool in
      support of a Metstab screen. In this platform, a dual-column setup running
      parallel chromatography was also implemented to reduce the bioanalytical cycle
      time for LC/MS/MS sample analysis. A set of 45 validation compounds was used to
      demonstrate the speed, quality and reproducibility of MS/MS method optimization,
      sample analysis, and data processing using this automated platform. Metstab
      results for the validation compounds in microsomes from multiple species (human,
      rat, mouse) showed good consistency within each batch, and also between batches
      conducted on different days. We have achieved and maintained a monthly throughput
      of 1300 compound assays representing 500 discrete compounds per instrument per
      month on this platform, and it has been used to generate metabolic stability data
      for more than 25 000 compounds to date with an overall success rate of more than
      95%.

PMID- 19399766
TI  - Complexation of late transition metal(II) ions (M = Co, Ni, Cu, and Zn) by a
      macrocyclic thiacrown ether studied by means of electrospray ionization mass
      spectrometry.
AB  - Electrospray ionization mass spectrometry (ESI-MS) is used to probe the metal
      binding selectivity of a macrocyclic thiacrown ether (C(44)H(32)S(20)) towards
      Co(II), Ni(II), Cu(II), and Zn(II). In homogeneous 1:1 v/v
      methanol/dichloromethane solutions, it is found that the thia ligand very
      selectively binds traces of copper even in the presence of an excess of the other
      metal ions. The large selectivity is ascribed to the redox-active nature of
      copper which enables a reduction from Cu(II) to Cu(I), occurring upon ESI-MS,
      whereas Co(II), Ni(II) and Zn(II) cannot undergo similar redox reactions.

PMID- 19399767
TI  - Analysis of urinary nucleosides as helper tumor markers in hepatocellular
      carcinoma diagnosis.
AB  - Hepatocellular carcinoma (HCC) is a common neoplasm in Taiwan, for which early
      diagnosis is difficult and the prognosis is usually poor. HCC is usually
      diagnosed by abdominal sonography and serum alpha-fetoprotein (AFP) detection.
      Modified nucleosides, regarded as indicators for the whole-body turnover of RNAs,
      are excreted in abnormal amounts in the urine of patients with malignancies and
      can serve as tumor markers. We analyzed the excretion patterns of urinary
      nucleosides from 25 HCC patients and 20 healthy volunteers by high-performance
      liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI
      MS/MS) under optimized conditions. The HPLC/ESI-MS/MS approach with selective
      reaction monitoring (SRM) allowed for the sensitive determination of nucleosides
      in human urine samples. The mean levels of the urinary nucleosides adenosine,
      cytidine, and inosine were significantly higher in HCC patients than healthy
      volunteers (average of 1.78-, 2.26-, and 1.47-fold, respectively). However, the
      mean levels of urinary 1-methyladenosine, 3-methylcytidine, uridine, and 2'
      deoxyguanosine were not significantly different. Combined with the determination
      of serum AFP levels, the higher levels of urinary adenosine, cytidine, and
      inosine may be additional diagnosis markers for HCC in Taiwanese patients.

PMID- 19399768
TI  - Time-dependent density functional theory study on the electronic excited-state
      geometric structure, infrared spectra, and hydrogen bonding of a doubly hydrogen
      bonded complex.
AB  - The geometric structures and infrared (IR) spectra in the electronically excited
      state of a novel doubly hydrogen-bonded complex formed by fluorenone and
      alcohols, which has been observed by IR spectra in experimental study, are
      investigated by the time-dependent density functional theory (TDDFT) method. The
      geometric structures and IR spectra in both ground state and the S(1) state of
      this doubly hydrogen-bonded FN-2MeOH complex are calculated using the DFT and
      TDDFT methods, respectively. Two intermolecular hydrogen bonds are formed between
      FN and methanol molecules in the doubly hydrogen-bonded FN-2MeOH complex.
      Moreover, the formation of the second intermolecular hydrogen bond can make the
      first intermolecular hydrogen bond become slightly weak. Furthermore, it is
      confirmed that the spectral shoulder at around 1700 cm(-1) observed in the IR
      spectra should be assigned as the doubly hydrogen-bonded FN-2MeOH complex from
      our calculated results. The electronic excited-state hydrogen bonding dynamics is
      also studied by monitoring some vibraitonal modes related to the formation of
      hydrogen bonds in different electronic states. As a result, both the two
      intermolecular hydrogen bonds are significantly strengthened in the S(1) state of
      the doubly hydrogen-bonded FN-2MeOH complex. The hydrogen bond strengthening in
      the electronically excited state is similar to the previous study on the singly
      hydrogen-bonded FN-MeOH complex and play important role on the photophysics of
      fluorenone in solutions.

PMID- 19399769
TI  - QSAR of antilipid peroxidative activity of substituted benzodioxoles using
      chemometric tools.
AB  - Search and development of new effective antioxidant molecules with improved
      activity is of both biological and commercial importance. In this background, we
      have modeled antioxidant activities of a series of benzodioxoles for their
      ability to inhibit lipid peroxidation (pC) using quantitative structure activity
      relationship (QSAR) technique. The QSAR models were developed using different
      chemometric tools such as GFA and G/PLS techniques. Two different sets of
      descriptors were used for developing these QSAR models. Molecular shape analysis
      (MSA) and spatial (charged partial surface area and shadow) descriptors were
      included in the one set, whereas quantum chemical (Mulliken charges on common
      atoms of the molecules calculated at the AM1 level) and physicochemical
      (hydrophobic parameter and molar refractivity) descriptors were included in the
      other set. All the models developed were validated internally by leave-one-out
      cross-validation and randomization techniques. The model predictivity was judged
      by their cross-validated squared correlation coefficient (Q(2)) and the modified
      r(2) (r(m(LOO)) (2)) values, whereas the robustness of the models was judged from
      the value of R(p) (2) (Roy and Paul, QSAR Comb Sci DOI:10.1002/qsar.200810130).
      The developed models suggest that the antilipid peroxidative activity of the
      molecules largely depends on the charges of the carbon atoms connected to the
      oxygen atoms of the dioxole ring. Besides this, the activity also depends on the
      charged surface area of the molecules and the dipole moment of the molecules.
      Presence of the methoxy substituents (ortho or meta) on the phenyl ring at the
      R(1) position of the benzodioxoles significantly lowers the antioxidant activity
      of these molecules.

PMID- 19399770
TI  - Increasing the time step with mass scaling in Born-Oppenheimer ab initio QM/MM
      molecular dynamics simulations.
AB  - Born-Oppenheimer ab initio QM/MM molecular dynamics simulation with umbrella
      sampling is a state-of-the-art approach to calculate free energy profiles of
      chemical reactions in complex systems. To further improve its computational
      efficiency, a mass-scaling method with the increased time step in MD simulations
      has been explored and tested. It is found that by increasing the hydrogen mass to
      10 amu, a time step of 3 fs can be employed in ab initio QM/MM MD simulations. In
      all our three test cases, including two solution reactions and one enzyme
      reaction, the resulted reaction free energy profiles with 3 fs time step and mass
      scaling are found to be in excellent agreement with the corresponding simulation
      results using 1 fs time step and the normal mass. These results indicate that for
      Born-Oppenheimer ab initio QM/MM molecular dynamics simulations with umbrella
      sampling, the mass-scaling method can significantly reduce its computational cost
      while has little effect on the calculated free energy profiles.

PMID- 19399771
TI  - Effect of metal ions on radical type and proton-coupled electron transfer
      channel: sigma-radical vs pi-radical and sigma-channel vs pi-channel in the imide
      units.
AB  - The mechanism of proton transfer (PT)/electron transfer (ET) in imide units, and
      its regulation by hydrated metal ions, was explored theoretically using density
      functional theory in a representative model (a nearly planar and cisoid complex
      between uracil and its N(3)-dehydrogenated radical, UU). In UU (sigma-radical),
      PT/ET normally occurs via a seven-center, cyclic proton-coupled sigma-electron
      sigma-channel transfer (PC(sigma)E(sigma)T) mechanism (3.8 kcal/mol barrier
      height) with a N(3)-->N(3') PT and an O(4)-->O(4') ET. Binding of hydrated metal
      ions to the dioxygen sites (O(2)/O(2') or/and O(4)/O(4')) of UU may significantly
      affect its PT/ET cooperative reactivity by changing the radical type (sigma
      radical <--> pi-radical) and ET channel (sigma-channel <--> pi-channel), leading
      to different mechanisms, ranging from PC(sigma)E(sigma)T, to proton-coupled pi
      electron sigma-channel transfer (PC(pi)E(sigma)T) to proton-coupled pi-electron
      pi-channel transfer (PC(pi)E(pi)T). This change originates from an alteration of
      the ordering of the UU moiety SOMO/HDMO (the singly occupied molecular orbital
      and the highest doubly occupied molecular orbital), induced by binding of the
      hydrated metal ions. It is a consequence of three associated factors: the
      asymmetric reactant structure, electron cloud redistribution, and fixing role of
      metal ions to structural backbone. The findings regarding the modulation of the
      PT/ET pathway via hydrated metal ions may provide valuable information for a
      greater understanding of PT/ET cooperative mechanisms, and an alternative way for
      designing imide-based molecular devices, such as molecular switches and molecular
      wires.

PMID- 19399772
TI  - Malpractice litigation and medical costs in the United States.
AB  - This paper examines the relationship of medical malpractice litigation and
      medical costs in the United States. We relate medical malpractice settlements to
      medical costs for 190 metro and non-metro areas in the United States over a 5
      year period and find that litigation is positively and significantly related to
      medical costs. Using a panel data set and a fixed-effects specification, the
      estimates indicate that malpractice litigation accounts for roughly 2-10% of
      medical expenditures, with the impact exceeding the dollar amount of settlements.

PMID- 19399774
TI  - First-principles calculations on the energetics, electronic structures and
      magnetism of SrFeO(2).
AB  - The electronic and magnetic properties of SrFeO(2) with different magnetic
      configurations have been calculated via the plane-wave pseudopotential density
      functional theory method, using the experimental lattice parameters. The results
      give an antiferromagnetic ground state for SrFeO(2) with an absolute magnetic
      moment agreeing very well with the experimental report. In comparison with the
      counterparts whose magnetic moments are parallel to the c axis, the structures
      with spin moments parallel to the a (or b) axis exhibit no observable preference
      in total energy, but show different density distributions of the Fe 3d(x(2)-y(2)
      ) and Fe 3d(z(2) ) states. The square-planar crystal field splits the Fe 3d
      orbitals into a high-level d(x(2)-y(2) ), a low d(z(2) ), and intermediate d(xy)
      and d(xz) or d(yz) components. The exchange splitting is larger than the crystal
      field splitting, resulting in the high-spin Fe 3d states. Referred to the triplet
      O(2), the O-vacancy formation energy from SrFeO(3) to SrFeO(2) has been deduced
      as well, along with its dependence on the temperature and O(2) partial pressure.

PMID- 19399773
TI  - Quality of life of family caregivers at 2 years after a relative's cancer
      diagnosis.
AB  - PURPOSE: Although a growing body of research has documented the quality of life
      (QOL) of cancer survivors beyond the initial phase of the survivorship, similar
      knowledge about family caregivers of cancer survivors remains limited. Thus, the
      current study aimed: (a) to characterize the multidimensional aspects of the QOL
      of family caregivers of cancer survivors at 2 years after the diagnosis and (b)
      to predict certain aspects of caregivers' QOL by their demographic and caregiving
      characteristics. METHODS: A total of 1635 caregivers of cancer survivors
      participated in the nationwide Quality of Life Survey for Caregivers.
      Multidimensional aspects of QOL were assessed, including mental and physical
      health, as well as psychological adjustment and spirituality at 2 years post
      diagnosis of their relatives' cancer. RESULTS: Family caregivers reported normal
      levels of QOL after 2 years post-diagnosis, except that they were more likely to
      experience increased awareness of spirituality than do individuals who personally
      experience a chronic illness. In addition, caregivers' age and income and care
      recipients' poor mental and physical functioning were significant predictors of
      their QOL at 2 years post-diagnosis. CONCLUSIONS: The findings suggest that
      younger, relatively poor caregivers who are providing care to relatives with poor
      mental and physical functioning may benefit from interventions to help in their
      spirituality and psychological and physical adjustment, 2 years after the initial
      cancer diagnosis. In addition, older, relatively poor caregivers may benefit from
      programs to reduce the physical burden of caregiving. These findings have
      implications for advancing public health research and practice.

PMID- 19399775
TI  - Quantification of hepcidin using matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry.
AB  - Hepcidin is known to be a key systemic iron-regulatory hormone which has been
      demonstrated to be associated with a number of iron disorders. Hepcidin
      concentrations are increased in inflammation and suppressed in hemochromatosis.
      In view of the role of hepcidin in disease, its potential as a diagnostic tool in
      a clinical setting is evident. This study describes the development of a matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) assay for the quantitative determination of hepcidin concentrations in
      clinical samples. A stable isotope labeled hepcidin was prepared as an internal
      standard and a standard quantity was added to urine samples. Extraction was
      performed with weak cation-exchange magnetic nanoparticles. The basic peptides
      were eluted from the magnetic nanoparticles using a matrix solution directly onto
      a target plate and analyzed by MALDI-TOF MS to determine the concentration of
      hepcidin. The assay was validated in charcoal stripped urine, and good recovery
      (70-80%) was obtained, as were limit of quantitation data (5 nmol/L), accuracy
      (RE <10%), precision (CV <21%), within -day repeatability (CV <13%) and between
      day repeatability (CV <21%). Urine hepcidin levels were 10 nmol/mmol creatinine
      in healthy controls, with reduced levels in hereditary hemochromatosis (P <
      0.000005) and elevated levels in inflammation (P < 0.0007). In summary a
      validated method has been developed for the determination of hepcidin
      concentrations in clinical samples.

PMID- 19399776
TI  - DFT study of the carbon- and nitrogen-pivot lariat crown ethers and their
      complexes with alkali metal cations: Na(+), K(+).
AB  - In this work, a quantum mechanical research of five lariat crown ethers(LCEs), 2
      methoxy-15-crown-5(A), N-methoxy-4-aza-15-crown-5(B), N-methoxy-4-aza-18-crown
      6(C), N-methoxyethyl-4-aza-18-crown-6(D), N,N'-bis(2-metho xyethyl)-4,13-diaza-18
      crown-6(E), which are based on either 15-crown-5 or 18-crown-6 frameworks and
      contain various pendant arms extending from either carbon or nitrogen atoms on
      the crown frameworks, had been done using density functional theory with B3LYP/6
      31G* method to obtain the electronic and geometrical structures of the LCEs and
      their complexes with alkali metal ions: Na(+) and K(+). The nucleophilicity of
      LCEs had been investigated by the Fukui functions. For complexes, the match
      between the cation and cavity size, the status of interaction between alkali
      metal ions and donor atoms in the LCEs, and the sidearm effect of the LCEs had
      been analyzed through the other calculated parameters, such as, highest occupied
      molecular orbital energy, lowest unoccupied molecular orbital energy, and energy
      gaps. In addition, the enthalpies of complexation reaction had been studied by
      the calculated thermodynamic data (298 K). The calculated results are all in a
      good agreement with the experimental data for the complexes.

PMID- 19399777
TI  - Free energy simulations reveal a double mutant avian H5N1 virus hemagglutinin
      with altered receptor binding specificity.
AB  - Historically, influenza pandemics have been triggered when an avian influenza
      virus or a human/avian reassorted virus acquires the ability to replicate
      efficiently and become transmissible in the human population. Most critically,
      the major surface glycoprotein hemagglutinin (HA) must adapt to the usage of
      human-like (alpha-2,6-linked) sialylated glycan receptors. Therefore,
      identification of mutations that can switch the currently circulating H5N1 HA
      receptor binding specificity from avian to human might provide leads to the
      emergence of pandemic H5N1 viruses. To define such mutations in the H5 subtype,
      here we provide a computational framework that combines molecular modeling with
      extensive free energy simulations. Our results show that the simulated binding
      affinities are in good agreement with currently available experimental data.
      Moreover, we predict that one double mutation (V135S and A138S) in HA
      significantly enhances alpha-2,6-linked receptor recognition by the H5 subtype.
      Our simulations indicate that this double mutation in H5N1 HA increases the
      binding affinity to alpha-2,6-linked sialic acid receptors by 2.6 +/- 0.7
      kcal/mol per HA monomer that primarily arises from the electrostatic
      interactions. Further analyses reveal that introduction of this double mutation
      results in a conformational change in the receptor binding pocket of H5N1 HA. As
      a result, a major rearrangement occurs in the hydrogen-bonding network of HA with
      the human receptor, making the human receptor binding pattern of double mutant
      H5N1 HA surprisingly similar to that observed in human H1N1 HA. These large scale
      molecular simulations on single and double mutants thus provide new insights into
      our understanding toward human adaptation of the avian H5N1 virus.

PMID- 19399778
TI  - Detection of interactions of the beta-amyloid peptide with small molecules
      employing transferred NOEs.
AB  - The interaction of pineal hormone melatonin, the histological dye thioflavin T,
      and the olive tree polyphenol oleuropein, with the 28 amino acid residue N
      terminal fragment of the beta-amyloid peptide (beta-AP) of Alzheimer's disease,
      [beta-AP(1-28)], was detected in solution through the observation of transferred
      NOEs (trNOEs) in 1D and 2D NOE spectroscopy (NOESY) experiments. The trNOE method
      is applied for the first time in the detection of interactions of soluble beta
      AP(1-28) with small molecules and may provide a means of screening for the
      identification of possible inhibitors of the formation of neurotoxic beta-AP
      assemblies.

PMID- 19399779
TI  - Trypsin-ligand binding free energies from explicit and implicit solvent
      simulations with polarizable potential.
AB  - We have calculated the binding free energies of a series of benzamidine-like
      inhibitors to trypsin with a polarizable force field using both explicit and
      implicit solvent approaches. Free energy perturbation has been performed for the
      ligands in bulk water and in protein complex with molecular dynamics simulations.
      The binding free energies calculated from explicit solvent simulations are well
      within the accuracy of experimental measurement and the direction of change is
      predicted correctly in all cases. We analyzed the molecular dipole moments of the
      ligands in gas, water and protein environments. Neither binding affinity nor
      ligand solvation free energy in bulk water shows much dependence on the molecular
      dipole moments of the ligands. Substitution of the aromatic or the charged group
      in the ligand results in considerable change in the solvation energy in bulk
      water and protein whereas the binding affinity varies insignificantly due to
      cancellation. The effect of chemical modification on ligand charge distribution
      is mostly local. Replacing benzene with diazine has minimal impact on the atomic
      multipoles at the amidinium group. We have also utilized an implicit solvent
      based end-state approach to evaluate the binding free energies of these
      inhibitors. In this approach, the polarizable multipole model combined with
      Poisson-Boltzmann/surface area (PMPB/SA) provides the electrostatic interaction
      energy and the polar solvation free energy. Overall the relative binding free
      energies obtained from the MM-PMPB/SA model are in good agreement with the
      experimental data.

PMID- 19399780
TI  - AutoDock4 and AutoDockTools4: Automated docking with selective receptor
      flexibility.
AB  - We describe the testing and release of AutoDock4 and the accompanying graphical
      user interface AutoDockTools. AutoDock4 incorporates limited flexibility in the
      receptor. Several tests are reported here, including a redocking experiment with
      188 diverse ligand-protein complexes and a cross-docking experiment using
      flexible sidechains in 87 HIV protease complexes. We also report its utility in
      analysis of covalently bound ligands, using both a grid-based docking method and
      a modification of the flexible sidechain technique.

PMID- 19399781
TI  - Trichogin GA IV: an antibacterial and protease-resistant peptide.
AB  - The antibacterial and hemolytic activities of the amphiphilic helical, membrane
      active, lipopeptaibol trichogin GA IV and its [Leu(11)-OMe] analogue were
      compared to those of the partially helical or non-helical 8-meric or 4-meric, C
      terminal short sequences, respectively. The study on trichogin GA IV was extended
      to several methicillin-resistant Staphylococcus aureus strains. Using a large set
      of enzymes, we also evaluated the resistance to proteolysis of all of the four
      peptides.

PMID- 19399782
TI  - Physical and psychological impairments of women with upper limb lymphedema
      following breast cancer treatment.
AB  - OBJECTIVE: The aim of the study was to identify factors associated with worse
      physical and emotional functioning of breast cancer survivors with upper
      extremity lymphedema. METHODS: 1250 sets of questionnaires consisting of WHO-DAS
      II, EORTC QLQ-C30, EORTC QLQ-BR23 and GHQ-30 were mailed to women who underwent a
      breast cancer surgery at the Lower Silesian Oncology Center in Poland between
      January 1998 and December 2005. RESULTS AND CONCLUSIONS: The response rate was
      33.47%. 117 women were included into a lymphedema group and 211 into a group
      without this complication. Women with lymphedema were more disabled (overall
      disability (DAS) score 39.78 versus 34.67; p<0.001), reported symptoms from the
      upper extremity (shoulder or arm pain and difficulties in arm movement) and from
      the operated breast (pain and swelling) 2-3 times more often, experienced poorer
      quality of life (global quality of life (QOL) score 0.50 versus 0.57; p=0.005)
      and higher psychological distress (GHQ score 10.61 versus 8.01; p=0.007) in
      comparison to breast cancer survivors without lymphedema. The factors associated
      with higher DAS score, higher GHQ score and lower QOL score in women with
      lymphedema were as following: pain in the upper limb (mainly shoulder and arm),
      pain in operated breast, difficulties with arm movement, localization of
      lymphedema within the hand or in operated breast, a history of
      dermatolymphangitis and of receiving chemotherapy. Severity of lymphedema,
      younger age, BMI and localization of lymphedema within the dominant limb were not
      considerably related to worse outcomes in these women.

PMID- 19399783
TI  - Most Influential Bioelectromagnetics Journal Paper by Citation award.

PMID- 19399784
TI  - Self-report of physical symptoms associated with using mobile phones and other
      electrical devices.
AB  - The aim of our work was to study the working-age population's self-reported
      physical symptoms associated with using mobile phones and other electrical
      devices. A qualitative method was applied using an open-ended question in a
      questionnaire, which included questions about the possible influence of new
      technical equipment on health. We then created subgroups of respondents for
      different self-reported symptoms associated with mobile phones and other
      electrical devices. The research questions were: (1) how the respondents
      described physical symptoms associated with using mobile phones and other
      electrical devices and (2) how the answers can be classified into subgroups based
      on symptoms or devices. We identified the following categories: (1) respondents
      with different self-reported symptoms which they associated with using mobile
      phones (headache, earache, or warmth sensations), (2) respondents who had skin
      symptoms when they stayed in front of a computer screen, (3) respondents who
      mentioned physical symptoms associated with using mobile phones and other
      electrical devices. Total prevalence of self-reported physical symptoms
      associated with using mobile phones and other electrical devices (categories 1
      and 2) was 0.7%. In the future it will be possible to obtain new knowledge of
      these topics by using qualitative methods.

PMID- 19399785
TI  - Surgery does not adversely affect survival in primary gastrointestinal lymphoma.
AB  - OBJECTIVE: To evaluate the impact of surgery on gastrointestinal lymphoma.
      METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was
      queried from 1973 to 2005. RESULTS: A total of 17,222 cases of PGIL were
      identified. The overall incidence of PGIL was approximately 1.505 cases per
      100,000. A significantly increasing incidence for PGIL was observed (APC = +4.67,
      P < 0.05). In the cases for which treatment data was available, resection
      occurred in roughly half of the patients. In univariate analysis, surgical
      extirpation did not improve survival (47 months vs. 76 months, P < 0.001), while
      radiation treatment improved median survival (77 months vs. 59 months, P <
      0.001). Multivariate analysis revealed increasing age and male gender as
      independent predictors of decreased overall survival. Tumor location also was a
      significant predictor of outcome. Large B-cell lymphoma type PGIL had a poorer
      prognosis than marginal zone B-cell lymphoma. By multivariate analysis, surgery
      was not found to increase the risk of death (HR = 0.99). CONCLUSIONS: No
      associated survival benefit for surgery in the treatment in gastrointestinal
      lymphoma was observed. Determination of lymphoma should preclude surgical
      resection. Nonetheless, inadvertent extirpative surgery or in association with
      perforation does not appear to increase mortality.

PMID- 19399786
TI  - Systemic inflammatory response predicts postoperative outcome in patients with
      liver metastases from colorectal cancer.
AB  - BACKGROUND: Few studies have investigated the Glasgow Prognostic Score (GPS) in
      patients with liver metastases from colorectal cancer (LM-CRC). METHODS: The GPS
      was calculated as follows: patients with both an elevated level of CRP (>10 mg/L)
      and hypoalbuminemia (Alb <35 g/L) were allocated a score of 2, and patients
      showing one or neither of these blood chemistry abnormalities were allocated a
      score of 1 or 0, respectively. RESULTS: Ninety-three patients were evaluated
      retrospectively. Kaplan-Meier analysis and log rank test revealed that a higher
      GPS predicted a higher postoperative death (P < 0.0001). Univariate analysis
      revealed that sex, number of hepatectomy, number of tumors, synchronous lung
      metastasis and CRP were associated with postoperative death. Multivariate
      analysis revealed that number of hepatectomy (odds ratio, 3.193; 95% CI, 1.093
      9.330; P = 0.0338), number of tumors (odds ratio, 2.946; 95% CI, 1.094-7.931; P =
      0.0325), synchronous lung metastasis (odds ratio, 3.424; 95% CI, 1.055-11.11; P =
      0.0404) and CRP (odds ratio, 4.509; 95% CI, 1.313-15.49; P = 0.0167) were
      associated with postoperative death. CONCLUSIONS: GPS is able to classify
      patients with LM-CRC into three independent groups. Among the selected factors,
      CRP is considered an important and high sensitive predictor of postoperative
      death in such patients.

PMID- 19399787
TI  - Botulinum toxin type A inhibits the growth of LNCaP human prostate cancer cells
      in vitro and in vivo.
AB  - INTRODUCTION AND OBJECTIVE: Botulinum toxin type A (BTA) intraprostatic injection
      induces an improvement of urinary symptoms related to benign prostatic
      hypertrophy (BPH). Infra-clinical prostate cancer (PCa) foci and pre-neoplasic
      lesions occur concomitantly with BPH in a significant number of patients. The
      objective of this study was to address whether BTA influences the growth of
      prostate tumors. METHODS: Proliferation of PC-3 and LNCaP cell lines exposed or
      not to BTA (Botox) was assessed and compared. Presence of synaptic vesicle 2
      (SV2) protein, the membrane receptor of BTA, was studied in both cell lines.
      After nude mice bearing LNCaP xenografts received intra-tumoral BTA or saline
      injection, tumor volume, serum PSA, histopathology and detection of apoptosis
      were comparatively assessed. RESULTS: BTA significantly reduced LNCaP cell
      proliferation and increased apoptosis in a dose-dependent manner but did not
      affect PC-3. The SV2 receptor was present in both cell lines at a ratio of 4:1
      (LNCaP/PC-3). One unit of BTA resulted in a significantly lower growth rate and
      slower PSA progression over 28 days compare to controls. The tumors were
      morphologically similar. There were significantly more apoptotic cells compared
      to controls. CONCLUSION: BTA inhibits the growth of LNCaP human PCa cells in
      vitro and in vivo. These findings indicate that intra-prostatic BTA injections to
      treat BPH are unlikely to promote the growth of co-existing infra-clinical PCa
      foci in men. A potential inhibitory effect of BTA on the growth of human PCa
      should be further studied.

PMID- 19399788
TI  - Liposomal gemcitabine (GemLip)-efficient drug against hormone-refractory Du145
      and PC-3 prostate cancer xenografts.
AB  - BACKGROUND: Gemcitabine (Gemc) is an efficient chemotherapeutic drug in various
      cancer types (e.g., pancreas) but has only limited effects on hormone-refractory
      prostate cancer (HRPCa). Since HRPCa cells are highly sensitive to even low doses
      of Gemc in vitro, the lack of clinical effects might be due to rapid degradation
      of Gemc by deaminases combined with impaired accumulation in tumor tissue and PCa
      cells. Liposomal formulation (GemLip) is expected to protect the entrapped
      cytotoxic substance from enzymatic degradation and furthermore augment its
      accumulation within tumor tissues due to an enhanced permeability of the tumor
      vessels. METHODS: Anti-tumoral and anti-metastatic activity of GemLip and Gemc
      were investigated in two luciferase-expressing, human hormone-refractory PC-3 and
      Du145 HRPCa xenograft models in immunodeficient mice. Tumor growth was monitored
      by in vivo luminescence imaging (orthotopic) or callipering (subcutaneous). Anti
      metastatic effects of treatment were determined by in vitro luciferase assay of
      the tissues. RESULTS: Tumor growth of subcutaneous Du145 xenografts was
      significantly inhibited only by GemLip (8 mg/kg: P = 0.014 and 6 mg/kg: P =
      0.011) but not by conventional Gemc (360 mg/kg). In contrast, growth of
      orthotopic PC-3 xenografts was significantly inhibited by both, GemLip (P =
      0.041) and Gemc (P = 0.002). The drugs furthermore strongly reduced spleen and
      liver metastases in this model. CONCLUSIONS: As shown by the very low efficient
      concentration of GemLip, liposomal entrapment of Gemc greatly enhances its
      activity. GemLip has, even at very low doses, a significant anti-tumoral and anti
      metastatic therapeutic effect in HRPCa xenografts in vivo and was beneficial even
      when the conventional Gemc failed.

PMID- 19399789
TI  - Social health insurance reexamined.
AB  - Social health insurance (SHI) is enjoying something of a revival in parts of the
      developing world. Many countries that have in the past relied largely on tax
      finance (and out-of-pocket payments) have introduced SHI, or are thinking about
      doing so. And countries with SHI already in place are making vigorous efforts to
      extend coverage to the informal sector. Ironically, this revival is occurring at
      a time when the traditional SHI countries in Europe have either already reduced
      payroll financing in favor of general revenues, or are in the process of doing
      so. This paper examines how SHI fares in health-care delivery, revenue
      collection, covering the formal sector, and its impacts on the labor market. It
      argues that SHI does not necessarily deliver good quality care at a low cost,
      partly because of poor regulation of SHI purchasers. It suggests that the costs
      of collecting revenues can be substantial, even in the formal sector where non
      enrollment and evasion are commonplace, and that while SHI can cover the formal
      sector and the poor relatively easily, it fares badly in terms of covering the
      non-poor informal sector workers until the economy has reached a high level of
      economic development. The paper also argues that SHI can have negative labor
      market effects.

PMID- 19399790
TI  - Doping control analysis for adrafinil and its major metabolites in human urine.
AB  - A new and reliable two-step liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) method in combination with gas chromatography/mass spectrometry
      (GC/MS) for the screening and confirmation of adrafinil and its major
      metabolites, modafinil and modafinil acid, in human urine has been developed and
      validated. The method involved reversed-phase C18 solid-phase extraction (SPE)
      cartridge extraction and MS analysis by means of LC/MS/MS and GC/MS. The study
      illustrated that the ESI capillary temperature played a key role in the formation
      of the protonated molecule. The limits of detection (LODs) of the developed
      method for the three compounds were lower than the minimum required performance
      limit (MRPL) of the World Anti-Doping Agency (WADA). The human urine samples
      obtained after the oral administration of modafinil and from the Beijing 2008
      Olympic Games were analyzed by using the described method, which has also been
      successfully applied to routine analyses and the WADA Proficiency Test.

PMID- 19399791
TI  - Epidemiology of hepatitis B in the United States.
AB  - Hepatitis B virus (HBV) remains an important cause of acute and chronic liver
      disease globally and in the United States. An encouraging trend is that the
      incidence of acute hepatitis B in the United States declined as much as 80%
      between 1987 and 2004, attributable to effective vaccination programs as well as
      universal precautions in needle use and in healthcare in general. Although
      encouraging, these decreases in acute infections have not translated into
      diminished prevalence or burden of chronic HBV infection. The prevalence for HBV
      in the United States has been estimated to be approximately 0.4%. However, these
      estimates have been based on surveys conducted in samples in which population
      groups with high prevalence of HBV infection, namely foreign-born minorities,
      were underrepresented. Voluntary screening data indicate prevalence in excess of
      15% in some of these groups. Recent immigration trends suggest a substantial
      increase in the number of Americans with chronic HBV infection. This trend is
      reflected in the health and economic burden associated with HBV infection. The
      number of outpatient visits and hospitalizations for a HBV-related diagnosis
      increased several-fold during the 1990s. Similarly, the total charges for
      hospitalizations have been estimated to have increased from $357 million in 1990
      to $1.5 billion in 2003. Most recent data indicate that death and liver
      transplant waitlist registration for HBV-related liver disease, which had been
      increasing, have now reached a plateau or started to decline. This encouraging
      trend might be attributable to recent advances in treatment for HBV infection;
      however, to the extent that the number of Americans living with chronic HBV is
      growing, careful clinical monitoring and continued epidemiologic surveillance
      remain important.

PMID- 19399792
TI  - The natural history of chronic hepatitis B virus infection.
AB  - Chronic hepatitis B virus (HBV) infection has a complicated course. Three phases
      are identified: an immune tolerant phase with high HBV DNA and normal alanine
      aminotransferase (ALT) levels associated with minimal liver disease; an immune
      active phase with high HBV DNA and elevated ALT levels with active liver
      inflammation; and an inactive phase with HBV DNA levels < 2000 IU/mL and normal
      ALT levels with minimal inflammation and fibrosis on liver biopsy. Affected
      persons can move progressively from one phase to the next and may revert
      backward. The primary adverse outcomes of chronic HBV infection are
      hepatocellular carcinoma (HCC) and cirrhosis. Published natural history studies
      were reviewed and ranked by the strength of evidence regarding the study design.
      Factors with the highest evidence of risk for development of HCC or cirrhosis
      from population-based prospective cohort studies include male sex, family history
      of HCC, HBV DNA level above 2000 IU/mL in persons above age 40, HBV genotypes C
      and F, and basal core promoter mutation. Those with the next highest level of
      evidence include aflatoxin exposure, and heavy alcohol and tobacco use. Improved
      methods to identify persons at highest risk of developing HCC or cirrhosis are
      needed to allow intervention earlier with antiviral therapy in appropriate
      patients. Future studies should include prospective follow-up of established
      population-based cohorts as well as new cohorts recruited from multiple centers
      stratified by HBV genotypes/subgenotypes and clinical phase to determine the
      incidence of the various HBV phases, HCC, and cirrhosis. Also, nested case
      control studies assessing immunological and host genetic factors among persons
      with active and inactive disease phases, HCC, and cirrhosis could be conducted
      using these types of cohorts.

PMID- 19399793
TI  - Monitoring during and after antiviral therapy for hepatitis B.
AB  - Recent studies suggest that long-term suppression of viral replication is
      critical to reducing the complications of chronic hepatitis B virus (HBV)
      infection. Monitoring for continued virological response during and after
      treatment is essential because current treatment options have limited success in
      achieving durable endpoints, and antiviral resistance may emerge during long-term
      therapy. Methods of monitoring treatment response include tests for serum
      aminotransferase levels, HBV DNA level, hepatitis B e antigen (HBeAg) and
      antibody (anti-HBe), hepatitis B surface antigen (HBsAg) or antibody (anti-HBs),
      and liver histology. Virological suppression and loss of HBeAg or HBsAg with or
      without seroconversion play a prominent role in decision-making regarding the
      success and duration of antiviral therapy. Guidelines recommend that testing for
      serum markers be repeated every 12-24 weeks during antiviral therapy and every 6
      12 months afterward. Recent data also suggest that serum HBV DNA levels should be
      assessed at weeks 12 and 24 of therapy, because early viral response may predict
      the likelihood of sustained response and antiviral resistance. The use of serum
      HBV DNA levels for this purpose requires an assay with a wide range of
      quantification, such as real-time polymerase chain reaction assays, which have a
      7-8 log(10) dynamic range. Newer, investigational methods for monitoring
      treatment response include quantitative measurement of HBsAg, HBeAg, and
      intrahepatic covalently closed circular DNA. CONCLUSIONS: Better methods for
      defining durable treatment endpoints are needed. Other areas requiring further
      research include the optimal treatment duration and the establishment of the
      optimal use of early viral kinetics for decision-making during antiviral therapy.

PMID- 19399795
TI  - Benefits and risks of nucleoside analog therapy for hepatitis B.
AB  - Five oral agents have been approved for the treatment of chronic hepatitis B,
      ranging in virological potency, clinical efficacy, barrier to resistance, and
      side-effect profile. The degree of histological, biochemical, and serological
      improvement with therapy generally corresponds to the degree of suppression of
      serum hepatitis B virus (HBV) DNA achieved with therapy. Conversely, for agents
      with a low barrier to resistance, the profundity of HBV DNA suppression in
      individual patients correlates inversely with the likelihood of resistance. The
      durability of hepatitis B e antigen (HBeAg) responses after a consolidation
      period of an additional 6-12 months of therapy is approximately 80% in western
      populations, lower in Asian populations. Loss of hepatitis B surface antigen
      (HBsAg) during a year of oral-agent therapy is limited, except with the most
      potent agents, but extending therapy for a second year and beyond can yield
      frequencies of HBsAg responses close to those reported in trials of interferon
      based therapy. The oral agents are approved for 1-2 years of therapy, but
      treatment is continued indefinitely in the majority of patients (except for the
      approximately 20% of patients who are HBeAg-reactive who achieve a durable HBeAg
      response). HBeAg responses and virological/biochemical benefit continue to be
      maintained and to increase with continued therapy beyond the first year. Data
      continue to accumulate supporting the link between long-term HBV DNA suppression
      and reduction in hepatic fibrosis, hepatic decompensation, and liver-related
      mortality. All the benefits of a single year of injectable peginterferon therapy
      can be achieved with the newer, low-resistance oral agents continued beyond the
      first year, without interferon side effects. Future studies are needed to develop
      drug regimens that are even more effective in achieving clinical endpoints, that
      are not hampered by resistance, and that are more confined in treatment duration
      but are more durable.

PMID- 19399794
TI  - Antiviral resistance and hepatitis B therapy.
AB  - The management of chronic hepatitis B currently rests with long-term therapy
      using oral nucleoside analogs. The major limitation of long-term therapy is
      antiviral resistance. Antiviral resistance is due to the high rate of mutations
      that can occur during hepatitis B virus (HBV) replication and the selection of
      these mutants due to a replication advantage in the presence of the antiviral
      agent. Indeed, high rates of antiviral resistance have been found with long-term
      use of lamivudine, in up to 76% of patients treated for 5 years or more. Rates of
      antiviral resistance are lower with adefovir therapy, approximately 30% at 5
      years. Newer more potent nucleoside analogs (tenofovir and entecavir) have proven
      to have much lower rates of antiviral resistance (<1% after 2 years in treatment
      naive subjects), but the long-term rates of resistance have yet to be fully
      defined. The appearance of these viral mutations (genotypic resistance) is
      usually followed by rises in HBV DNA levels (virological breakthrough) and then
      by rises in serum aminotransferase levels (biochemical breakthrough). The
      appearance of antiviral resistance can be accompanied by a transient but
      occasionally severe exacerbation of the underlying liver disease which in some
      instances has led to acute liver failure. Combinations of nucleoside analogs may
      offer an approach to preventing antiviral resistance, but the efficacy and safety
      of this approach have yet to be shown. A future research priority is to identify
      new agents active against HBV that target different steps in the viral life-cycle
      and might provide effective means to circumvent the antiviral resistance of
      nucleoside analogs.

PMID- 19399796
TI  - Benefits and risks of combination therapy for hepatitis B.
AB  - In successful antiviral therapy of hepatitis B, drug combinations, particularly
      combinations without cross-resistance, can delay or prevent the emergence of drug
      resistant mutants. Because drug-resistant mutants are archived and may limit
      future therapeutic options, prevention is important for long-term therapeutic
      efficacy. Additionally, combining drugs may achieve synergistic or additive
      antiviral effects compared with single drug therapy. Undesirable aspects of
      combination therapy include higher treatment costs and possibly lower adherence
      rates (due to pill number or complexity of regimen). Potentially harmful effects
      of combination therapy include higher rates of side effects, reduced efficacy due
      to drug competition, and the risk of multidrug-resistant hepatitis B virus (HBV)
      if combination therapy is insufficient to prevent resistance. Combination therapy
      has been shown to reduce the rate of drug resistance in chronic hepatitis B, but
      only when drugs with a low barrier to resistance are used (lamivudine, adefovir).
      Combination therapies may achieve greater degrees of HBV DNA suppression, but
      this has not been associated with higher rates of seroconversion (hepatitis B e
      antigen or hepatitis B surface antigen) compared to single drug therapy. The
      benefit of combination therapy has yet to be demonstrated with agents that are
      associated with a high barrier to resistance (tenofovir, entecavir). The use of
      combination therapy is recommended in specific patient groups: those with
      decompensated cirrhosis, those coinfected with human immunodeficiency virus and
      HBV who are on antiretroviral therapy, those who have undergone liver
      transplantation, and those with drug-resistant HBV infection. There is
      insufficient evidence to recommend combination therapy as first-line therapy for
      all patients with chronic hepatitis B.

PMID- 19399797
TI  - Clinical outcomes in adults with chronic hepatitis B in association with patient
      and viral characteristics: A systematic review of evidence.
AB  - We systematically reviewed the literature on the extent to which population
      characteristics or clinical features predict groups of individuals likely to
      develop advanced liver disease or die from chronic infection with hepatitis B
      virus (HBV). We searched Medline to include studies with reported cirrhosis,
      liver failure, liver cancer, or death outcomes after at least 1 year of follow-up
      from the measurement of predictive factors (age, age at infection, geographic
      location, race/ethnicity, sex, positive family history, presence of coinfections,
      HBV viral level, change in hepatitis B e antigen [HBeAg] status, genotype, HBV
      mutations, nonalcoholic fatty liver disease, alcohol consumption, liver enzymes,
      and liver biopsy finding). Evidence from 41 included articles suggested that
      cirrhosis, higher HBV viral level, and male sex were consistently associated with
      significantly increased risk of death and liver cancer. Evidence about the role
      of HBV genotype, HBeAg status, age and duration of infection, coinfections with
      hepatitis C virus, human immunodeficiency virus, hepatitis delta virus, and
      alanine aminotransferase levels were limited and inconsistent, but were deemed
      promising to identify patients at higher risk of clinical outcomes. Adults with
      chronic hepatitis B had increased risk for poorer health outcomes compared to the
      general population; however, the magnitude of risk varied greatly depending on
      baseline patient and disease characteristics, and typically clinical outcomes
      required many years to become manifest. Many adults with chronic hepatitis B had
      low absolute risks of clinical outcomes and likely would not benefit from
      immediate treatment. Baseline patient and disease characteristics provide
      important information about the risk of clinical outcomes and should be
      incorporated into monitoring or treatment decisions.

PMID- 19399798
TI  - Liver biopsy findings in chronic hepatitis B.
AB  - Liver biopsy plays a central role in treatment algorithms in patients with
      hepatitis B and remains the gold standard for evaluating hepatic pathology. The
      pathology of hepatitis B is diverse and reflects the natural history of
      infection. An acute hepatitic pattern with lobular disarray is seen in acute
      infection, during acute flares of disease, and with acute hepatitis D
      superinfection. In chronic hepatitis B, inflammation is less pronounced in the
      immune-tolerant phase and is prominent during immune-mediated viral clearance.
      Active inflammation appears to be the driving force for development of fibrosis.
      Inflammatory grades and fibrosis stage are assigned as is done for hepatitis C.
      Although current management guidelines recommend liver biopsies only in select
      patients based on age, viral levels, and hepatitis B e antigen status, these
      clinical and biochemical parameters do not show consistent correlations with
      liver histology. Liver biopsy also helps identify preneoplastic lesions including
      large cell and small cell change. Unlike in other causes of chronic hepatitis,
      immunostains are widely used and can help determine the phase of infection. Liver
      biopsies can also identify additional pathology that may contribute to liver
      disease such as steatohepatitis, iron overload, autoimmune hepatitis, and drug
      induced injury. Thus, liver biopsy can play an important role in staging and
      grading chronic hepatitis B and should be more widely used in assessing the need
      for therapy.

PMID- 19399799
TI  - Indications for therapy in hepatitis B.
AB  - Increased treatment options that are more efficacious and safe and new knowledge
      on the natural history of chronic hepatitis B virus (HBV) infection have expanded
      the indications for therapy in hepatitis B. The question is no longer "Who should
      be treated?" but "When should treatment be initiated?" Treatment is clearly
      indicated in patients with life-threatening liver disease (acute liver failure,
      decompensated cirrhosis, or severe hepatitis flare) and in those with compensated
      cirrhosis and high levels of serum HBV DNA. For patients with precirrhotic liver
      disease, treatment indications should be based on clinical, biochemical, or
      histological evidence of liver disease, such as elevated alanine aminotransferase
      (ALT) levels, abnormal histology, and high levels of serum HBV DNA. The cutoff
      for ALT and HBV DNA values are constantly being revised and should be set at a
      lower level for older patients who may have been infected for a longer period of
      time. High serum HBV DNA levels persisting for a few decades are associated with
      increased risk of clinical outcomes, but there is insufficient data to support
      the initiation of treatment based on high serum HBV DNA alone, particularly in
      young patients, those with persistently normal ALT levels, and those with a
      single high HBV DNA level. The decision to initiate treatment at the time of
      assessment or to defer treatment should take into consideration other factors
      such as desire to start a family, occupational requirement, family history of
      hepatocellular carcinoma, access to care and insurance coverage, and commitment
      to long-term treatment and medication compliance. All patients who are not
      initiated on treatment should continue to be monitored so treatment can be
      started if and when the indication arises.

PMID- 19399800
TI  - Endpoints of therapy in chronic hepatitis B.
AB  - Because clearance of hepatitis B virus (HBV) infection is rarely, if ever,
      achievable, the goals of therapy necessarily focus on prevention of bad clinical
      outcomes. Ideally, therapies would be shown to prevent tangible clinical
      endpoints like development of cirrhosis, end-stage liver disease and
      hepatocellular carcinoma. However, these endpoints typically take years or
      decades to occur and are therefore impractical targets for clinical trials which
      last only 1-2 years. As a result, surrogate biomarkers that are believed to
      correlate with long-term outcome are used to evaluate therapy. Of the clinical,
      biochemical, serological, virological, and histological endpoints that have been
      evaluated, none has been shown to be ideal on its own. Symptoms are uncommon and
      aminotransferase levels fluctuate spontaneously. Loss of hepatitis B e antigen
      (HBeAg) has been the traditional therapeutic endpoint; however, the indefinite
      durability off treatment and the emergence of HBeAg-negative disease have made it
      inadequate as the sole goal of therapy. Loss of hepatitis B surface antigen is
      associated with improved clinical outcomes, but it is rarely achieved with
      current therapies. Suppression of viral replication, as measured by serum HBV DNA
      levels, has become the major goal of therapy, particularly if maintained off
      therapy. Although useful, the significance of viral levels depends on the stage
      of disease, degree of liver damage, and the type of therapy. Finally, liver
      biopsy, often considered the gold standard, is invasive, prone to sampling error,
      and may take years to change significantly.At present, there is no ideal
      biomarker for evaluation of therapies for hepatitis B. Future research should be
      directed at development and validation of surrogate markers that accurately
      predict or reflect clinically relevant outcomes of chronic hepatitis B.

PMID- 19399801
TI  - Hepatitis B virus DNA levels and outcomes in chronic hepatitis B.
AB  - Serum hepatitis B virus (HBV) DNA levels can fluctuate markedly during the course
      of chronic HBV infection. Both case-control and cohort studies have shown a
      significant, dose-response association between serum HBV DNA levels measured at
      the time of initial evaluation and the subsequent risk of cirrhosis. A similar
      direct relationship has been shown for the risk of hepatocellular carcinoma (HCC)
      in cross-sectional, case-control, and cohort studies. Interventional studies have
      shown a strong correlation between the indices of disease activity seen on liver
      biopsy and levels of serum HBV DNA. These studies have also shown that reduction
      in HBV DNA levels correlate strongly with improvements in liver histology. For
      patients with HCC, prognosis (including risk of death, metastasis, and recurrence
      following surgery) is worse with higher serum HBV DNA levels. The preponderance
      of the evidence in the published literature demonstrates that serum HBV DNA level
      is an important and independent risk factor for disease progression in chronic
      hepatitis B. The relative importance of serial HBV DNA measurements, the loss of
      hepatitis B e and surface antigens, as well as the emergence of HBV mutants in
      the progression of chronic hepatitis B, especially in young patients, is an
      important need for future research.

PMID- 19399802
TI  - Side effects of long-term oral antiviral therapy for hepatitis B.
AB  - The aim of this review is to summarize the safety profile of the five approved
      oral nucleoside analogs used to treat chronic hepatitis B virus (HBV) infection,
      focusing on both the class adverse effects and those that have been reported with
      individual agents, as well as their safety in pregnancy. All nucleoside analogs
      have a "Black Box" warning because of their potential for inhibition of human DNA
      polymerase gamma involved in mitochondrial DNA replication. A reduction in
      intracellular mitochondrial DNA levels can lead to varying clinical
      manifestations of mitochondrial toxicity (i.e., neuropathy, myopathy, lactic
      acidosis), but these side effects are rarely reported with the oral antiviral
      agents active against HBV. Adefovir and tenofovir are associated with a dose
      dependent but usually reversible proximal renal tubular toxicity. For these
      reasons, patients receiving these agents should be monitored for renal toxicity
      and the dose modified for renal insufficiency. Prolonged use of tenofovir has
      also been reported to lead to reduced bone mineral density in patients with human
      immunodeficiency virus infection, but prospective studies in patients with HBV
      infection are lacking. Telbivudine treatment is associated with moderate serum
      creatine phosphokinase elevations in up to 12% of patients. There have been few
      prospective studies on the safety of nucleoside analogs during pregnancy.
      According to the Antiretroviral Pregnancy Registry, the incidence of birth
      defects associated with lamivudine and tenofovir use during pregnancy is not
      increased. Studies on the safety of long-term therapy with the nucleoside
      analogs, alone and in combination, are needed as are further studies of children,
      the elderly, pregnant women, and patients with renal insufficiency.

PMID- 19399803
TI  - Reactivation of hepatitis B.
AB  - Reactivation of hepatitis B refers to the abrupt increase in hepatitis B virus
      (HBV) replication in a patient with inactive or resolved hepatitis B.
      Reactivation can occur spontaneously, but more typically is triggered by
      immunosuppressive therapy of cancer, autoimmune disease, or organ
      transplantation. Reactivation can be transient and clinically silent, but often
      causes a flare of disease that can be severe resulting in acute hepatic failure.
      Most instances of reactivation resolve spontaneously, but if immune suppression
      is continued, re-establishment of chronic hepatitis occurs which can lead to
      progressive liver injury and cirrhosis. The best-described instances of
      reactivation occur in hepatitis B surface antigen (HBsAg) carriers with inactive
      or minimally active disease who are given cancer chemotherapy for lymphoma or
      leukemia. Typically, serum HBV DNA rises during chemotherapy, followed by a
      disease flare and HBV DNA clearance with immune reconstitution after chemotherapy
      is stopped. Special forms of reactivation occur after solid organ and bone marrow
      transplantation in which chronic infection often results. Several randomized,
      placebo-controlled trials have shown that reactivation can be prevented by
      antiviral prophylaxis. Routine prophylaxis is therefore recommended for persons
      with HBsAg undergoing cancer chemotherapy or transplantation, but major questions
      remain. Which patients should be screened for HBsAg and should all be treated?
      Which antiviral should be used and for how long? Should persons with resolved
      hepatitis B without HBsAg receive prophylaxis? Future research should address the
      underlying molecular mechanisms of reactivation as well as its optimal means of
      diagnosis, treatment, and prevention in different patient populations.

PMID- 19399804
TI  - National Institutes of Health consensus development conference statement:
      management of hepatitis B.

PMID- 19399805
TI  - The hepatitis B research network.

PMID- 19399806
TI  - Benefits and risks of interferon therapy for hepatitis B.
AB  - Alpha interferon is the only licensed drug for hepatitis B with immunomodulatory
      as well as viral inhibitory properties. Potential advantages of interferon
      compared to nucleoside analogs include a lack of drug resistance, a finite and
      defined treatment course, and a higher likelihood for hepatitis B surface antigen
      (HBsAg) clearance. Approximately 30% of hepatitis B e antigen (HBeAg)-positive
      and 40% of HBeAg-negative cases have a sustained virological response (when
      defined as HBeAg seroconversion and/or hepatitis B virus (HBV) DNA levels below
      20,000 copies/mL, respectively) 6 months after completion of a 48-week course of
      peginterferon alfa-2a These responses remain durable in 80% and 50% of cases,
      respectively, when evaluated several years later. Recent studies have shown that
      changes in HBsAg and HBeAg concentration during treatment predict sustained
      virological response and serial monitoring of HBsAg is helpful in predicting
      HBsAg clearance. HBeAg-positive patients with genotype A have higher rates of
      HBeAg and HBsAg clearance, whereas HBeAg-negative patients with genotype D have
      the lowest rate of response to interferon therapy. Long-term follow-up of
      virological responders to either standard alpha interferon or peginterferon has
      demonstrated a progressive increase in the rate of HBsAg clearance, particularly
      in patients who were initially HBeAg-positive. Future studies need to address if
      specific virological benchmarks during therapy can be used to tailor treatment
      duration. CONCLUSION: Peginterferon alfa has a place as first-line therapy of
      hepatitis B in patients who are carefully selected on the basis of pretreatment
      serum HBV DNA and aminotransferase levels, safety considerations, and viral
      genotype.

PMID- 19399807
TI  - Hepatitis B and hepatocellular carcinoma.
AB  - Chronic infection with the hepatitis B virus has been linked epidemiologically to
      the development of hepatocellular carcinoma for more than 30 years. Although the
      mechanisms by which chronic hepatitis B viral infection results in hepatocellular
      carcinoma are unclear, there is good evidence that the virus itself exerts a
      direct hepatocarcinogenic effect, and this has implications for prevention.
      First, programs of universal infant vaccination have been shown to be effective
      in reducing the rate of hepatocellular carcinoma among children. This benefit
      should be translated into adulthood among vaccine recipients. Second, it has been
      suggested that antiviral therapy against hepatitis B may reduce the risk of
      hepatocellular carcinoma. Antiviral therapy against hepatitis B is effective in
      causing prolonged lowering of serum levels of hepatitis B virus DNA. There are
      emerging data showing that prolonged antiviral therapy may reduce the risk of
      hepatocellular carcinoma among certain patients with chronic hepatitis B.

PMID- 19399810
TI  - Special populations with hepatitis B virus infection.
AB  - Treatment of patients with chronic hepatitis B virus (HBV) infection who have
      advanced disease or comorbidities can be challenging, and recommendations may
      differ from standard guidelines. Among the special populations that merit
      specific consideration are patients with compensated or decompensated cirrhosis,
      organ transplantation, acute hepatitis B, pregnancy, coinfection with hepatitis C
      and/or D virus, chronic renal failure, and children. Major advances have been
      made in management of many of these special populations because of recent
      increasing availability of oral nucleosides, which are generally well tolerated
      and highly effective despite presence of other morbidities or viral infections.
      Also important have been changes in the management of hepatitis B during the peri
      liver transplantation period that allows for prevention of reinfection in the
      majority of cases. However, much remains to be done to determine which patients
      should be treated and which should be monitored on no specific therapy. Outcomes
      of chronic HBV infection in persons with coinfection and in children have varied
      from different areas of the world, but it is not clear whether these differences
      are due to host and racial differences or to viral genotypic differences. Further
      studies are particularly needed in assessing the safety and efficacy of therapy
      in pregnant women, in children, and in patients with hepatitis D and C virus
      coinfection.

PMID- 19399811
TI  - Hepatitis B: the virus and disease.
AB  - Hepatitis B virus (HBV) infects more than 300 million people worldwide and is a
      common cause of liver disease and liver cancer. HBV, a member of the
      Hepadnaviridae family, is a small DNA virus with unusual features similar to
      retroviruses. HBV replicates through an RNA intermediate and can integrate into
      the host genome. The unique features of the HBV replication cycle confer a
      distinct ability of the virus to persist in infected cells. Virological and
      serological assays have been developed for diagnosis of various forms of HBV
      associated disease and for treatment of chronic hepatitis B infection. HBV
      infection leads to a wide spectrum of liver disease ranging from acute (including
      fulminant hepatic failure) to chronic hepatitis, cirrhosis, and hepatocellular
      carcinoma. Acute HBV infection can be either asymptomatic or present with
      symptomatic acute hepatitis. Most adults infected with the virus recover, but 5%
      10% are unable to clear the virus and become chronically infected. Many
      chronically infected persons have mild liver disease with little or no long-term
      morbidity or mortality. Other individuals with chronic HBV infection develop
      active disease, which can progress to cirrhosis and liver cancer. These patients
      require careful monitoring and warrant therapeutic intervention. Extrahepatic
      manifestations of HBV infection are rare but can be difficult to diagnose and
      manage. The challenges in the area of HBV-associated disease are the lack of
      knowledge in predicting outcome and progression of HBV infection and an unmet
      need to understand the molecular, cellular, immunological, and genetic basis of
      various disease manifestations associated with HBV infection.

PMID- 19399812
TI  - Recommendations for identification and public health management of persons with
      chronic hepatitis B virus infection.
AB  - Early identification of persons with chronic HBV infection enables infected
      persons to receive necessary care to prevent or delay onset of liver disease, and
      enables the identification and vaccination of susceptible household contacts and
      sex partners, interrupting ongoing transmission. Testing has been recommended
      previously to enable primary prevention of HBV infection among close contacts for
      pregnant women, household contacts and sex partners of HBV-infected persons,
      persons born in countries with hepatitis B surface antigen (HBsAg) prevalence of
      more than 8%, persons who are the source of blood or body fluid exposures that
      might warrant postexposure prophylaxis (e.g., needlestick injury to a healthcare
      worker or sexual assault), and to enable appropriate treatment for infants born
      to HBsAg-positive mothers and persons infected with human immunodeficiency virus.
      Recently, with the increasing availability of efficacious hepatitis B treatment,
      the Centers for Disease Control and Prevention published new recommendations for
      public health evaluation and management for chronically infected persons and
      their contacts and extended testing recommendations to include persons born in
      geographic regions with HBsAg prevalence of greater than 2%, men who have sex
      with men, and injection drug users. Patient and provider education, developing
      partnerships between health departments and community organizations, and other
      resources will be needed to assure appropriate populations are tested and care
      provided for persons newly identified as HBsAg-positive.

PMID- 19399813
TI  - Hepatitis B and human immunodeficiency virus coinfection.
AB  - Coinfection with human immunodeficiency virus-1 (HIV) and hepatitis B virus (HBV)
      is common; worldwide, an estimated 10% of HIV-infected persons have chronic
      hepatitis B. Because the incidence of traditional acquired immunodeficiency
      syndrome-related opportunistic infections has decreased with successful anti-HIV
      therapy, liver disease has emerged as a leading cause of morbidity and mortality
      in HIV-infected individuals. HIV infection negatively impacts all phases of the
      natural history of hepatitis B leading to increased rates of persistent
      infection, higher HBV DNA levels, lower rates of hepatitis B e antigen loss,
      increased cirrhosis and liver-related mortality, and increased risk of
      hepatocellular carcinoma at lower CD4+ T cell counts. The management of hepatitis
      B in HIV infection is complicated by the dual activity of several nucleoside
      analogs, the more rapid development of lamivudine-resistant HBV in patients who
      are HIV-positive, and the paucity of studies in this population. Until further
      research emerges on the optimal treatment for this population, data from HBV
      monoinfected persons will need to be extrapolated to the HIV-HBV coinfected
      population. Further research is also needed to determine the mechanism(s) for the
      increased liver disease progression and optimal treatment goals.

PMID- 19399814
TI  - NIH consensus development conference: management of Hepatitis B. Introduction.

PMID- 19399815
TI  - Evaluation of the patient with hepatitis B.
AB  - The initial evaluation of a patient with hepatitis B virus infection should
      attempt to assess the disease activity and stage in the context of the known
      natural history of this infection and to properly assess the needs for treatment
      and surveillance. In addition to a medical history and focused physical
      examination, the initial evaluation usually requires serological, biochemical,
      and virological tests to confirm the diagnosis as well as an imaging study to
      establish a baseline for future monitoring. A liver biopsy is generally not
      needed but can provide useful information on prognosis, need for surveillance for
      hepatocellular carcinoma (HCC), and whether to recommend therapy. Follow-up
      monitoring is aimed at determining disease progression, development of
      complications, and reassessing the need for treatment. Monitoring frequency
      should be determined based on the activity and stage of disease. Initiation of
      screening for HCC should be based on age, race, sex, family history, and stage
      and duration of disease. The current recommended method of screening and
      surveillance for HCC is by ultrasonography and alpha-fetoprotein measurements
      every 6-12 months. Prospective studies are needed to evaluate the role of
      longitudinal application of noninvasive assays of fibrosis, such as serum
      fibrosis markers and transient elastography. Better biomarkers and imaging
      modalities are needed for early detection of HCC. Finally, studies are needed to
      better refine the indications and to balance the risks and benefits of antiviral
      therapy.

PMID- 19399816
TI  - Cellular mRNA expressions of anti-oxidant factors in the blood of preeclamptic
      women.
AB  - OBJECTIVE: To assess the alterations of mRNA expressions associated with
      oxidative stress in the cellular component of blood from pregnant women with pre
      eclampsia. METHODS: Peripheral blood samples were obtained from pregnant women
      with and without pre-eclampsia. Cellular RNA was subjected to a reverse
      transcription polymerase chain reaction (PCR) assay in order to examine the mRNA
      distribution among women with pre-eclampsia (n = 24) and control subjects (n =
      24) during 35-41 weeks of gestation. The data were analyzed by non-parametric
      statistics. RESULTS: Significant differences between the pre-eclampsia subjects
      and the controls were observed in the gene expressions associated with oxidative
      stress. Lower values in the pre-eclampsia group were found for heme oxygenase
      (HO)-1, HO-2, catalase and superoxide dismutase (SOD). The HO-1, HO-2 and the
      catalase levels significantly correlated with proteinuria, and the HO-2 level
      with systolic blood pressure. CONCLUSION: Significantly lower concentrations of
      HO-1, HO-2, SOD and catalase are found in the cellular component of blood from
      pre-eclamptic patients. The values correlate with the severity of pre-eclampsia.
      These findings indicate that enhanced oxidative stress and a decrease in the
      number of anti-oxidant enzymes may be associated with pre-eclampsia.

PMID- 19399818
TI  - Synthesis of new modified truncated peptides and inhibition of glycogen
      phosphorylase.
AB  - The first solution state structural analysis (NMR) of the C-terminal sequence of
      human G(L) that binds to glycogen phosphorylase a (GPa), PEWPSYLGYEKLGPYY-NH(2)
      (1), showed it to be in a random coil conformation. This was supported by
      molecular dynamics simulation (modelled in solution) using NAMD 2.6. The
      conformational ambiguity of the peptide makes the structural arrangement of the
      peptide (and internal residues) strongly dependent on the environment. Thirteen
      tetra-peptide fragments of the C-terminal sequence, YEKLG-NH(2), and the
      corresponding tri- and di-peptide sequences were used in a fragment screen
      against GPa. Compound 2 (H-GPYY-NH(2)) did not give an IC(50) value, whereas
      PEWPSYLGYEKLGPYY-NH(2) (1) displayed an IC(50) of 34 microM against GPa.
      Truncated peptides derived from 1, (EKL-NH(2), EKLG-NH(2), and AcEKNH(2))
      inhibited GPa (21%, 32%, 63%, respectively at 22 mM). These studies suggest key
      residues within the peptide chain have additional molecular interactions with
      GPa. The interaction of intra-sequence residues in combination with the terminal
      residues of PEWPSYLGYEKLGPYY with GPa may form the basis for the design of new
      inhibitors of GPa.

PMID- 19399820
TI  - Greater leftward lateralization of the inferior frontal gyrus in second language
      learners with higher syntactic abilities.
AB  - There is a great individual variability for acquiring syntactic knowledge in a
      second language (L2). Little is, however, known if there is any anatomical basis
      in the brain for individual differences in syntactic acquisition. Here we
      examined brain structures in 95 nonnative speakers of English, including 78 high
      school students and 17 adult international students. We found a significant
      correlation between the performance of a syntactic task and leftward
      lateralization of a single region in the triangular part (F3t) of the inferior
      frontal gyrus, which has been proposed as the grammar center. Moreover, this
      correlation was independent of the performance of a spelling task, age, gender,
      and handedness. This striking result suggests that the neural basis for syntactic
      abilities in L2 is independent of that for lexical knowledge in L2, further
      indicating that the individual differences in syntactic acquisition are related
      to the lateralization of the grammar center.

PMID- 19399821
TI  - Selectively deposited silver coatings on gold-capped silicon nanowires for
      surface-enhanced Raman spectroscopy.
AB  - Gold caps on silicon nanowires are selectively coated with silver by
      autometallography (electroless deposition). Changing the conditions of silver
      deposition, a variety of different coating morphologies can be produced [figure:
      see text]. The different silver coating morphologies are investigated in terms of
      their capabilities for surface enhanced Raman scattering (SERS) experiments.Gold
      caps on silicon nanowires are hemispherical and only a few tens of nanometers in
      diameter when grown from metal catalysts by the vapor-liquid-solid growth
      mechanism using chemical vapor deposition. These gold caps are capable of
      enhancing Raman signals based on the surface-enhanced Raman scattering effect.
      The Raman signal can be enhanced even further (by at least one order of
      magnitude) when silver is selectively deposited onto these gold caps by
      autometallography (electroless deposition). By changing the silver deposition
      conditions, different coating morphologies can be realized on the gold caps that
      range from very thin, smooth layers to uneven and extremely rough coatings. The
      SERS signal enhancement and the spatial homogeneity of the achievable enhancement
      are compared for the different silver coatings using a model dye molecule.

PMID- 19399822
TI  - Reversible structural modulation of Fe-Pt bimetallic surfaces and its effect on
      reactivity.
AB  - Tunable surface: The surface structure of the Fe-Pt bimetallic catalyst can be
      reversibly modulated between the iron-oxide-rich Pt surface and the Pt-skin
      structure with subsurface Fe via alternating reduction and oxidation treatments
      (see figure). The regenerated active Pt-skin structure is active in reactions
      involving CO and/or O.

PMID- 19399823
TI  - DFT/CCSD(T) investigation of the interaction of molecular hydrogen with carbon
      nanostructures.
AB  - The interaction of molecular hydrogen with carbon nanostructures is investigated
      within the DFT/CC correction scheme. The DFT/CC results are compared with the
      benchmark calculations at the CCSD(T) level of theory for benzene and
      naphthalene, and at the MP2 level for the more extended systems. The DFT/CC
      method offers a reliable alternative to the highly correlated ab initio
      calculations at a cost comparable to the standard DFT method. The results for
      H(2) adsorbed on graphene as well as single-wall carbon nanotubes (SWCNT) are
      presented. The DFT/CC binding energy on graphene of 5.4 kJ mol(-1) is in good
      agreement with experiment (5.00+/-0.05 kJ mol(-1)). For (10,10)-SWCNT, the H(2)
      molecule is mostly stabilized inside the tube with an estimated binding energy of
      7.2 kJ mol(-1).

PMID- 19399824
TI  - Prenatal diagnosis of haemophilia A in China.
AB  - OBJECTIVES: To develop a one-tube fluorescent multiplexed polymerase chain
      reaction (PCR) method to perform prenatal diagnosis of haemophilia A (HA).
      METHODS: Peripheral blood samples were collected from 220 women and from members
      of five families with proven HA. One-tube fluorescent PCR and capillary
      electrophoresis were performed to investigate four short tandem repeats (STRs) in
      intron 1, 13, 22 and 24 (STR1, STR13, STR22 and STR24, respectively) in FVIII.
      RESULTS: Our analysis revealed 7 different alleles for STR1, 10 for STR13, 7 for
      STR22 and 9 for STR24. The heterozygosity rate (HR) for STR1, 13, 22 and 24 was
      34.6%, 49.6%, 43.6% and 38.2%, respectively. The HR was 75.0% (165/220) when
      these four markers were combined. Prenatal diagnosis was made for five male
      foetuses. Four foetuses were identified as affected ones of HA. The STR results
      were consistent with the data we obtained by PCR of St14 VNTR (DXS52) and DNA
      sequencing, which showed that one foetus harbours a mutation in exon12 (1804C >
      T) in FVIII. CONCLUSION: This study demonstrates that multiplex fluorescent
      analysis of four STRs is a rapid and simple method to perform genetic diagnosis
      of HA in families with a history of this disorder.

PMID- 19399825
TI  - Addressing between-study heterogeneity and inconsistency in mixed treatment
      comparisons: Application to stroke prevention treatments in individuals with non
      rheumatic atrial fibrillation.
AB  - Mixed treatment comparison models extend meta-analysis methods to enable
      comparisons to be made between all relevant comparators in the clinical area of
      interest. In such modelling it is imperative that potential sources of
      variability are explored to explain both heterogeneity (variation in treatment
      effects between trials within pairwise contrasts) and inconsistency (variation in
      treatment effects between pairwise contrasts) to ensure the validity of the
      analysis.The objective of this paper is to extend the mixed treatment comparison
      framework to allow for the incorporation of study-level covariates in an attempt
      to explain between-study heterogeneity and reduce inconsistency. Three possible
      model specifications assuming different assumptions are described and applied to
      a 17-treatment network for stroke prevention treatments in individuals with non
      rheumatic atrial fibrillation.The paper demonstrates the feasibility of
      incorporating covariates within a mixed treatment comparison framework and using
      model fit statistics to choose between alternative model specifications. Although
      such an approach may adjust for inconsistencies in networks, as for standard meta
      regression, the analysis will suffer from low power if the number of trials is
      small compared with the number of treatment comparators.

PMID- 19399827
TI  - Characterisation of the thermal, spectroscopic and drug dissolution properties of
      mefenamic acid and polyoxyethylene-polyoxypropylene solid dispersions.
AB  - The aim of this study was to investigate the solubility of mefenamic acid (MA), a
      highly cohesive, poorly water-soluble drug in a copolymer of polyoxyethylene
      polyoxypropylene (Lutrol F68), and to understand the effect drug polymer
      solubility has on in vitro dissolution of MA. Solid dispersions (SD) of MA were
      prepared by a hot melt method, using Lutrol F68 as a thermoplastic polymeric
      platform. High-speed differential scanning calorimetry (Hyper-DSC), Raman
      spectroscopy, powder X-ray diffractometry (PXRD) and hot-stage/fluorescence
      microscopy were used to assess the solubility of the drug in molten and solid
      polymer. Drug dissolution studies were subsequently conducted on single-phase
      solid solutions and biphasic SD using phosphate buffer pH 6.8 as dissolution
      media. Solubility investigations using Hyper-DSC, Raman spectroscopy and hot
      stage microscopy suggested MA was soluble in molten Lutrol F68 up to a
      concentration of 35% (w/w). Conversely, the solubility in the solid-state matrix
      was limited to <15% (w/w); determined by Raman spectroscopy, PXRD and
      fluorescence microscopy. As expected the dissolution properties of MA were
      significantly influenced by the solubility of the drug in the polymer matrix. At
      a concentration of 10% (w/w) MA (a single phase solid solution) dissolution of MA
      in phosphate buffer 6.8 was rapid, whereas at a concentration of 50% (w/w) MA
      (biphasic SD) dissolution was significantly slower. This study has clearly
      demonstrated the complexity of drug-polymer binary blends and in particular
      defining the solubility of a drug within a polymeric platform. Moreover, this
      investigation has demonstrated the significant effect drug solubility within a
      polymeric matrix has upon the in vitro dissolution properties of solid
      polymer/drug binary blends.

PMID- 19399828
TI  - Multiple three-dimensional mammalian cell aggregates formed away from solid
      substrata in ultrasound standing waves.
AB  - Single and multiple three-dimensional cell aggregates of human red blood cells
      (RBCs) and HepG2 cells were formed rapidly in low mega-Hertz ultrasound standing
      wave fields of different geometries. A single discoid aggregate was formed in a
      half-wavelength pathlength resonator at a cell concentration sufficient to
      produce a 3D structure. Multiple cell aggregates were formed on the axis of a
      cylindrical resonator with a plane transducer (discoid aggregates); in a
      resonator with a tubular transducer and in the cross-fields of plane and tubular
      transducers and two plane orthogonal transducers (all cylindrical aggregates).
      Mechanically strong RBC aggregates were obtained by crosslinking with wheat germ
      agglutinin (WGA, a lectin). Scanning electron microscopy showed aggregate surface
      porous structures when RBCs were mixed with WGA before sonication and tighter
      packing when ultrasonically preformed aggregates were subsequently exposed to a
      flow containing WGA. HepG2 cell aggregates showed strong accumulation of F-actin
      at sites of cell-cell contact consistent with increased mechanical stability. The
      aggregates had a porous surface, and yet confocal microscopy revealed a tight
      packing of cells in the aggregate's inner core.

PMID- 19399830
TI  - Glial cell-derived neurotrophic factor increases migration of human
      chondrosarcoma cells via ERK and NF-kappaB pathways.
AB  - Invasion of tumor cells is the primary cause of therapeutic failure in the
      treatment of malignant chondrosarcomas. Glial cell-derived neurotrophic factor
      (GDNF) plays a crucial role in migration and metastasis of human cancer cells.
      Integrins are the major adhesive molecules in mammalian cells. Here we found that
      GDNF directed the migration and increased cell surface expression of alphav and
      beta3 integrin in human chondrosarcoma cells. Pretreated of JJ012 cells with MAPK
      kinase (MEK) inhibitors PD98059 or U0126 inhibited the GDNF-mediated migration
      and integrin expression. Stimulation of cells with GDNF increased the
      phosphorylation of MEK and extracellular signal-regulating kinase (ERK). In
      addition, NF-kappaB inhibitor (PDTC) or IkappaB protease inhibitor (TPCK) also
      inhibited GDNF-mediated cells migration and integrin up-regulation. Stimulation
      of cells with GDNF induced IkappaB kinase (IKKalpha/beta) phosphorylation,
      IkappaB phosphorylation, p65 Ser(536) phosphorylation, and kappaB-luciferase
      activity. Furthermore, the GDNF-mediated increasing of kappaB-luciferase activity
      was inhibited by PD98059, U0126, PDTC and TPCK or MEK, ERK, IKKalpha, and IKKbeta
      mutants. Taken together, these results suggest that the GDNF acts through
      MEK/ERK, which in turn activates IKKalpha/beta and NF-kappaB, resulting in the
      activations of alphavbeta3 integrin and contributing the migration of human
      chondrosarcoma cells.

PMID- 19399829
TI  - Looking toward basic science for potential drug discovery targets against
      community-associated MRSA.
AB  - The difficulties to find a conventional vaccine against Staphylococcus aureus and
      the increasing resistance of S. aureus to many antibiotics demand the exploration
      of novel therapeutic options, such as by targeting virulence determinants and
      using specific antibodies in an antitoxin-like approach. Community-associated
      methicillin-resistant S. aureus (CA-MRSA) strains have recently emerged
      predominantly in the US, causing epidemic outbreaks of mostly skin and soft
      tissue infections, but also more dramatic and sometimes fatal diseases. MRSA is
      now the most frequent cause of death by a single infectious agent in the US. The
      fact that, at least in the US, CA-MRSA infections are almost entirely due to one
      sequence type, USA300, gives researchers a novel, unique chance to focus on one
      clone in their efforts to analyze pathogenesis in a clinically important S.
      aureus. While the molecular underpinnings of the exceptional virulence and
      transmissibility of USA300 are not yet well understood, recent findings indicate
      that increased expression of widespread virulence determinants and acquisition of
      mobile genetic elements have to be considered. Delineating the relative
      importance of virulence determinants in USA300 and other important clinical
      strains is a key endeavor needed to develop a potential antitoxin for CA-MRSA
      disease.

PMID- 19399831
TI  - Medicinal chemistry and therapeutic potential of muscarinic M3 antagonists.
AB  - Muscarinic acetylcholine receptors belong to the G-protein-coupled receptors
      family. Currently five different receptor subtypes have been identified and
      cloned. M3 receptor subtypes are coupled to G(q) family proteins and increase
      phosphatidyl inositol hydrolysis and calcium release from internal stores. They
      are widely distributed both in the central nervous system and in the periphery.
      At the central level, M3 receptor subtypes are involved in modulation of
      neurotransmitter release, temperature homeostasis, and food intake, while in the
      periphery they induce smooth muscle contraction, gland secretion, indirect
      relaxation of vascular smooth muscle, and miosis. The main therapeutic
      applications of M3 antagonists include overactive bladder (OAB), chronic
      obstructive pulmonary disease (COPD), and pain-predominant irritable bowel
      syndrome (IBS). The introduction of selective M3 antagonists has not improved
      clinical efficacy compared with the old non-selective antimuscarinics but has
      reduced the rate of adverse events mediated by the blockade of cardiac M2
      receptors (tachycardia) and central M1 receptors (cognitive impairment). Improved
      tolerability has been obtained also with controlled release or with inhaled
      formulations. However, there is still a need for safer M3 antagonists for the
      treatment of COPD and better-tolerated and more effective compounds for the
      therapy of OAB. New selective muscarinic M3 antagonists currently in early
      discovery and under development have been designed to address these issues.
      However, as M3 receptors are widely located in various tissues including salivary
      glands, gut smooth muscles, iris, and ciliary muscles, further clinical
      improvements may derive from the discovery and the development of new compounds
      with tissue rather than muscarinic receptor subtype selectivity.

PMID- 19399832
TI  - Preparation and recycling of aqueous two-phase systems with pH-sensitive
      amphiphilic terpolymer PADB.
AB  - In this study, a novel pH-sensitive terpolymer PADB was synthesized by random
      terpolymerization of 2-(dimethylamino) ethyl methacrylate, acrylic acid, and
      butyl methacrylate. The terpolymer PADB could form aqueous two-phase systems
      (ATPS) with a light-sensitive terpolymer PNBC, which was synthesized in our
      laboratory, using n-isopropylacrylamide, n-butyl acrylate, chlorophyllin sodium
      copper salt as monomers. More than 97% of the PADB terpolymer could be recovered
      by adjusting the pH to isoelectric point (PI) 4.1. The terpolymer PNBC could be
      recovered by using light radiation at 488 nm, with recovery ratio of 98%. BSA and
      lysozyme were partitioned in the PNBC-PADB ATPS to examine this new system. It
      was found that the partition coefficient of BSA and lysozyme could reach 4.46 and
      0.49 in the systems, respectively.

PMID- 19399834
TI  - Harmonic scalpel in the treatment of Zenker's diverticulum.
AB  - OBJECTIVES/HYPOTHESIS: To describe the transoral treatment of Zenker's
      diverticulum with a harmonic scalpel and review the initial outcomes of patients
      treated with this technique. STUDY DESIGN AND METHODS: Retrospective study of 25
      patients with symptomatic Zenker's diverticula who were treated endoscopically
      with the harmonic scalpel (Ethicon Endo-Surgery, Inc, Cincinnati, OH). Electronic
      medical records were reviewed. Extracted data included outpatient clinic notes,
      operative reports, hospital summaries, and follow-up visits. RESULTS: All
      identified patients (N = 25) were treated successfully and safely with the
      harmonic scalpel. All patients were observed overnight, and 21 (84%) were
      dismissed the day after surgery. One patient with a history of cardiac disease
      had a non-ST-elevation myocardial infarction, one patient had aspiration
      pneumonia, and two patients had chest pain (both stayed for complete evaluations
      with negative findings). One patient had subcutaneous emphysema. No patients had
      hemorrhage, infection, mediastinitis, or death in the postoperative period. The
      average length of follow-up was 10.3 months. One patient had a recurrent
      diverticulum that was treated with an open surgical technique. CONCLUSIONS:
      Various treatment options are available for Zenker's diverticulum. There has been
      a trend toward less invasive techniques, and the harmonic scalpel is one useful
      treatment option. This review demonstrates that the harmonic scalpel is a safe
      and effective alternative. Longer follow-up time is needed to assess long-term
      success and incidence of recurrence with this new technique.

PMID- 19399835
TI  - Long-term great auricular nerve morbidity after sacrifice during parotidectomy.
AB  - OBJECTIVES/HYPOTHESIS: To clarify the extent and patient perspectives of great
      auricular nerve (GAN) morbidity and recovery after nerve sacrifice during
      parotidectomy 4 to 5 years after surgery. STUDY DESIGN: Prospective series.
      METHODS: Twenty-two patients who underwent parotidectomy with GAN sacrifice and
      were previously studied for GAN sensory outcome during the first postoperative
      year. We performed light touch sensation tests on each patient to develop an ink
      map representing anesthesia and paresthesia in the GAN sensory territory;
      patients also completed an outcomes questionnaire. RESULTS: Nineteen (86%) of 22
      patients completed follow-up. One patient completed the questionnaire over the
      phone. The prevalence and average areas of anesthesia and paresthesia decreased
      since the first postoperative year according to sensory testing and patient
      scoring. At 4 to 5 years, 47% (9 of 19) of the patients had anesthesia, 58% (11
      of 19) had paresthesia, and 26% (5 of 19) had neither anesthesia nor paresthesia
      during sensory testing. Patients reported that the GAN dysfunction brought them
      no to mild inference with their daily activities. At a mean point of 2 years, 70%
      (14 of 20) patients felt that their sensory symptoms had either completely abated
      or stabilized. CONCLUSIONS: The posterior branch of the GAN should be preserved
      if it does not compromise tumor resection. If this is not possible, the patient
      and surgeon should be comforted in that only minor, if any, long-term disability
      will ensue. Laryngoscope, 2009.

PMID- 19399836
TI  - Gamma knife radiosurgery for vestibular schwannomas: results of hearing
      preservation in relation to the cochlear radiation dose.
AB  - OBJECTIVES/HYPOTHESIS: This study was designed to evaluate hearing preservation
      after gamma knife radiosurgery (GKRS) and to determine the relation between
      hearing preservation and cochlear radiation dose in patients with a sporadic
      vestibular schwannoma (VS). METHODS: Prospective study involving patients
      suffering from VS who received GKRS from June 2003 until November 2007. Pure tone
      and speech audiometry were conducted before and after GKRS. The thresholds at
      pure tone audiometry were taken as a measure of hearing. Pure tone average (PTA)
      was defined as the mean threshold at 0.5 kHz, 1.0 kHz, 2.0 kHz, and 4.0 kHz.
      Hearing was classified according to the 2003 consensus meeting in Tokyo.
      Stereotactic surgery was performed using a Leksell 4C Gamma Knife (Elekta,
      Stockholm, Sweden). RESULTS: A total of 69 patients were included in the study.
      Mean tumor size was 17 mm. Mean marginal dose at the tumor was 11.0 Gy (range,
      9.3 Gy-12.3 Gy), mean maximal dose was 19.7 Gy (range, 16 Gy-25.5 Gy). Mean
      maximal dose at the cochlea was 10.27 Gy (range, 3.1 Gy-16.1 Gy), and mean
      minimal dose at the cochlea was 2.6 Gy (range, 0.9 Gy-7.4 Gy). Mean PTA before
      GKRS was 43 dB (standard deviation [SD] 20 dB), mean PTA after GKRS was 63 dB (SD
      30 dB). Mean interval between pre-GKRS audiometry and GKRS was 8.0 months.
      Between GKRS and post-GKRS audiometry, mean interval was 14.2 months. Hearing was
      considered to be preserved (max +1 class, Tokyo classification) in 52 (75%) of 69
      patients. However, only 32 patients had class A, B, or C (serviceable hearing)
      before GKRS. Within this group, only 13 patients (41%) had a hearing class A, B,
      or C after GKRS. A significant relation was found between the maximal cochlear
      dose and the difference in PTA before and after GKRS. CONCLUSIONS: Hearing
      preservation is correlated to the maximal radiation dose at the cochlea. The
      purpose of developing GKRS techniques was to avoid collateral damage in healthy
      tissues. This study emphasizes the need for exact radiation planning to reduce
      the cochlear radiation dose if the hearing is to be preserved. Laryngoscope,
      2009.

PMID- 19399838
TI  - Sexual behavior in female western lowland gorillas (Gorilla gorilla gorilla):
      evidence for sexual competition.
AB  - Previous research in gorillas suggests that females engage in post-conception
      mating as a form of sexual competition designed to improve their own reproductive
      success. This study focused on sexual behaviors in a newly formed group of
      western lowland gorillas (Gorilla gorilla gorilla) housed at Zoo Atlanta. All
      females engaged in mating outside their conceptive periods, although there was
      individual variation in the frequency of the behavior. An analysis of the
      presence/absence of sexual behavior found females, regardless of reproductive
      condition, were more likely to engage in sexual behavior on days when other
      females were sexually active. On these "co-occurrence" days, females were
      significantly more likely to solicit the silverback, but copulations did not
      differ from expectation. The results find further evidence for sexual competition
      among female gorillas and suggest that this may occur throughout their
      reproductive cycle rather than only during pregnancy.

PMID- 19399840
TI  - Is prediction of outcome with magnetic resonance imaging in postresuscitation
      coma achievable and accurate?

PMID- 19399839
TI  - Varicella zoster virus is not a disease-relevant antigen in multiple sclerosis.
AB  - Herpesvirions and varicella zoster virus (VZV) DNA were recently reported in all
      15 cerebrospinal fluid (CSF) samples from patients with relapsing-remitting
      multiple sclerosis (MS) obtained within 1 week of exacerbation. Using identical
      electron microscopic and polymerase chain reaction techniques, including
      additional primer sets representing different regions of the VZV genome, we found
      no herpesvirions or VZV DNA in MS CSF or acute MS plaques. Although enzyme-linked
      immunosorbent assay analysis demonstrated a higher titer of VZV antibody in MS
      CSF than in inflammatory control samples, recombinant antibodies prepared from
      clonally expanded MS CSF plasma cells did not bind to VZV. VZV is not a disease
      relevant antigen in MS.

PMID- 19399841
TI  - Opportunistic infections and other risks with newer multiple sclerosis therapies.
AB  - The introduction of newer therapies for the treatment of multiple sclerosis has
      generated considerable optimism. That optimism has been tempered by the potential
      risks of these therapies, such as the risk for progressive multifocal
      leukoencephalopathy. A review of the possible causes of reactivation of JC virus
      in this population has illustrated the need to better understand the untoward
      effects of monoclonal antibody therapies and other immunomodulatory therapies
      currently being contemplated for use in multiple sclerosis. These drugs alter the
      immune response at different sites, and most, if not all, affect more than one
      aspect of host immunity. Drawing from existing experience with the use of these
      immunomodulatory therapies in other conditions and that available from the
      limited experience with multiple sclerosis, we review their potential untoward
      effects. The latter include a predisposition to opportunistic and community
      acquired infections, an altered response to vaccination, the development of
      cancers, and the appearance of autoimmune diseases. The identification of
      progressive multifocal leukoencephalopathy as a risk of therapy is relatively
      straightforward in light of its rarity and high morbidity and mortality, but a
      relatively slight increased risk for more common and less disabling disorders may
      be overlooked. Determining the actual risk frequency for many of these
      complications will likely require careful postmarketing surveillance.

PMID- 19399842
TI  - Use of chitosan membrane associated with polypropylene mesh to prevent peritoneal
      adhesion in rats.
AB  - The correction of wall abdominal defects often requires the use of implants such
      as polypropylene meshes. In spite of presenting good tissue acceptance, these
      biomaterials can migrate to adjacent viscera, promote enterocutaneos fistulas,
      tissue adherence and visceral erosions. In this work, the barrier effect of
      chitosan films associated with polypropylene meshes on adhesion formation
      experimentally induced in Wistar rats was evaluated. The animals were divided
      into two groups with 10 animals each. Animals in the CPP group were implanted
      with chitosan films associated with polypropylene meshes, whereas the ones in the
      PP group received only polypropylene meshes. After 8 days, the animals were
      submitted to euthanasia using CO(2) and a descriptive study focusing adhesion
      formation, visceral involvement with sutures and mesh peritonization was
      performed. Also, subimplanted material was collected for histopathology analysis.
      The results showed that the CPP group presented weak adhesions to the omentum
      over the stitch knots in eight animals. In all animals, the meshes were
      peritonized, not allowing their visualization after removing the chitosan films.
      In the PP group, six animals presented intestinal adhesions to the meshes and, in
      one of them, hepatic adhesion to the mesh was observed, besides omentum adhesion
      on more than 50% of the mesh area. The protective effect of chitosan films when
      sutured over polypropylene meshes, as well as no exacerbation of inflammation
      associated to the peritoneal lesions was statistically demonstrated. Therefore,
      chitosan films can indeed minimize the formation of peritoneal adhesions induced
      by polypropylene meshes in rats.

PMID- 19399843
TI  - Causes of shear sensitivity of the toxic dinoflagellate Protoceratium
      reticulatum.
AB  - Dinoflagellates have proven extremely difficult to culture because they are
      inhibited by low-level shear forces. Specific growth rate of the toxic
      dinoflagellate Protoceratium reticulatum was greatly decreased compared with
      static control culture by intermittent exposure to a turbulent hydrodynamic
      environment with a bulk average shear rate that was as low as 0.3 s(-1).
      Hydrodynamic forces appeared to induce the production of reactive oxygen species
      (ROS) within the cells and this caused peroxidation of cellular lipids and
      ultimately cell damage. Exposure to damaging levels of shear rate correlated with
      the elevated level of lipoperoxides in the cells, but ROS levels measured
      directly by flow cytometry did not correlate with shear induced cell damage. This
      was apparently because the measured level of ROS could not distinguish between
      the ROS that are normally generated by photosynthesis and the additional ROS
      produced as a consequence of hydrodynamic shear forces. Continuously subjecting
      the cells to a bulk average shear rate value of about 0.3 s(-1) for 24-h caused
      an elevation in the levels of chlorophyll a, peridinin and dinoxanthin, as the
      cells apparently attempted to counter the damaging effects of shear fields by
      producing pigments that are potential antioxidants. In static culture, limitation
      of carbon dioxide produced a small but measureable increase in ROS. The addition
      of ascorbic acid (0.1 mM) to the culture medium resulted in a significant
      protective effect on lipid peroxidation, allowing cells to grow under damaging
      levels of shear rates. This confirmed the use of antioxidant additives as an
      efficient strategy to counter the damaging effects of turbulence in
      photobioreactors where shear sensitive dinoflagellates are cultivated.

PMID- 19399844
TI  - Vascular endothelial growth factor gene transfer for diabetic polyneuropathy.

PMID- 19399845
TI  - Amifostine protection against induced DNA damage in gamma-irradiated Escherichia
      coli cells depend on recN DNA repair gene product activity.
AB  - Amifostine is the most effective radioprotector known and the only one accepted
      for clinical use in cancer radiotherapy. In this work, the antigenotoxic effect
      of amifostine against gamma-rays was studied in Escherichia coli cells deficient
      in DNA damage repair activities. Assays of irradiated cells treated with
      amifostine showed that the drug reduced the genotoxicity induced by radiation in
      E. coli wild-type genotypes and in uvr, recF, recB, recB-recC-recF mutant
      strains, but not in recN defective cells. Thus, the mechanism of DNA protection
      by amifostine against gamma-radiation-induced genotoxicity appears to involve
      participation of the RecN protein that facilitates repair of DNA double-strand
      breaks. The results are discussed in relation to amifostine's chemopreventive
      potential.

PMID- 19399846
TI  - Dynamic compression modulates chondrocyte proliferation and matrix biosynthesis
      in chitosan/gelatin scaffolds.
AB  - It is well-documented that dynamical compression stimulates biosynthesis of
      extracellular biomacromolecules in cartilage explant or in chondrocyte/hydrogel
      systems. The object of this study was to apply high-strain dynamic compression to
      cell-seeded elastic scaffolds for articular cartilage tissue engineering. Rabbit
      chondrocytes had been cultured in chitosan/gelatin scaffolds for 3 days before
      dynamic compression. The chondrocyte/scaffold constructs were subjected to short
      term (3 or 9 h) or long-term (6 h/day for 3 weeks) cyclic compression with 40%
      strain and 0.1 Hz. The expression of type II collagen and aggrecan was
      upregulated after 3-h of compression when compared with the free-swelling
      samples. Furthermore, long-term culture under dynamic compression facilitated
      cellular proliferation and deposition of glycosaminoglycan. Our results suggest
      that high-strain dynamic compression combined with elastic scaffolds might
      benefit articular cartilage tissue engineering.

PMID- 19399847
TI  - Evaluation of tooth analogs and type of restoration on the fracture resistance of
      post and core restored incisors.
AB  - OBJECTIVE: In in vitro tests, metals and resins are frequently used as
      substitutes for human teeth. This study aims at determining the suitability of
      various materials for substituting human incisors in load capability tests.
      METHOD: Veneering composite (Adoro; n = 16) and non-precious CoCr-alloy (NPA; n =
      16) were used for manufacturing 32 identical specimens based on the model of a
      maxillary central incisor resin tooth (Morita). Sixteen human incisors served as
      a control group. After root canal treatment, all specimens were restored with
      fiber-reinforced composite posts and core build-ups. For each group, eight
      specimens were chosen randomly and restored either with identical NPA crowns or
      with all-ceramic crowns. Specimens were exposed to thermal cycling and mechanical
      loading (TCML) until failure. Statistical analysis was conducted using the
      Kruskal-Wallis test and the Bonferroni-adjusted Mann Whitney U-test. RESULTS: In
      ceramic crowns, the highest median fracture resistance was found in alloy tooth
      substitutes (430 N) and natural incisors (426 N), which both showed a
      significantly higher fracture resistance than composite tooth substitutes (162
      N). In alloy crowns, alloy tooth substitutes exhibited the highest fracture
      resistance (348 N), but no statistically significant difference could be detected
      between natural incisors (158 N) and composite tooth substitutes (117 N). No
      artificial tooth substitute showed fracture patterns similar to those of natural
      incisors. SIGNIFICANCE: Mechanical parameters are significantly influenced by the
      type of restoration and the restorative material used. In in vitro tests, the
      range of artificial tooth substitutes suitable for the replacement of human
      incisors is limited by load capability.

PMID- 19399848
TI  - Malathion-induced oxidative stress, cytotoxicity, and genotoxicity in human liver
      carcinoma (HepG2) cells.
AB  - Malathion is an organophosphate pesticide that is known for its high toxicity to
      insects and low to moderate potency to humans and other mammals. Its toxicity has
      been associated with the inhibition of acetylcholinesterase activity, leading to
      the interference with the transmission of nerve impulse, accumulation of
      acetylcholine at synaptic junctions, and subsequent induction of adverse health
      effects including headache, dizziness, nausea, vomiting, bradycardia, and miosis.
      Oxidative stress (OS) has been reported as a possible mechanism of malathion
      toxicity in humans. Hence, the aim of this study was to examine the role of OS in
      malathion-induced cytotoxicity and genotoxicity. To achieve this goal, MTT, lipid
      peroxidation, and single cell gel electrophoresis (Comet) assays were performed,
      respectively, to evaluate the levels of cell viability, malondialdehyde (MDA)
      production, and DNA damage in human liver carcinoma (HepG(2)) cells. Study
      results indicated that malathion is mitogenic at lower levels of exposure, and
      cytotoxic at higher levels of exposure. Upon 48 h of exposure, the average
      percentages of cell viability were 100% +/- 11%, 117% +/- 15%, 86% +/- 15%, 35%
      +/- 9%, and 27% +/- 7% for 0, 6, 12, 18, and 24 mM, respectively. In the lipid
      peroxidation assay, the concentrations of MDA produced were 12.55 +/- 0.16, 20.65
      +/- 0.27, 31.1 +/- 0.40, 34.75 +/- 0.45, and 15.1 +/- 0.20 muM in 0, 6, 12, 18,
      and 24 mM malathion, respectively. The Comet assay showed a significant increase
      in DNA damage at the 24 mM malathion exposure. Taken together, our results
      indicate that malathion exposure at higher concentrations induces cytotoxic and
      genotoxic effects in HepG(2) cells, and its toxicity may be mediated through OS
      as evidenced by a significant production of MDA, an end product of lipid
      peroxidation.

PMID- 19399849
TI  - Accumulation of toxic metals (Pb and Cd) in the sea urchin Diadema aff.
      antillarum Philippi, 1845, in an oceanic island (Tenerife, Canary Islands).
AB  - This document shows the results obtained from a study on the concentration of
      toxic heavy metals in the internal tissue and exoskeleton of sea urchins,
      collected from their natural habitat. The levels of lead and cadmium were
      measured by Graphite Furnace Atomic Absorption Spectrometry. The mean
      concentrations of lead and cadmium in the internal tissue were 304.04 and 260.54
      microg/kg respectively, whereas in the shell they were 185.02 and 142.48
      microg/kg. We also performed a statistical analysis of the differences in the
      distribution of metals between their exoskeleton and their internal content, a
      correlation study of the metal content in internal tissue and shell and sampling
      areas, and a correlation study between the metal content and sample size. Since
      the sea urchin Diadema antillarum presents a wide range of variation in metal
      content, this study suggests that this species is an excellent bioindicator of
      heavy metal contamination.

PMID- 19399850
TI  - Regeneration of ischemic heart using hyaluronic acid-based injectable hydrogel.
AB  - An injectable hydrogel was applied to regenerate a myocardial infarction and
      functional recovery of the heart. A myocardial infarction was induced in rat by
      circumflex artery ligation. A hyaluronic acid-based hydrogel was injected into
      the epicardium of the infarcted area. Then, cardiac functions and regeneration of
      the myocardium in sham-operated (SHAM), myocardial infarction (MI), and gel
      injected group (GEL) (n = 6) were evaluated 4 weeks after the injection.
      Measurements of the thickness of the wall showed that the thickness in the GEL
      group increased by up to 200% compared with that in the MI group (p < 0.001). The
      infarcted area of the left ventricular in the GEL group decreased by 53% compared
      with the MI group (p < 0.001). The number of arterioles and capillaries in the
      border zone of the GEL group increased by 152% and 148%, whereas the apoptotic
      index decreased by 42% (p < 0.05). Measurement of the heart functions, such as
      ejection fraction, arterial elastance (Ea), dP/dt max, and dP/dt min, indicated
      that the injection of a hydrogel significantly facilitated the functional
      recovery compared with the MI group. Because of its simplicity, easy
      applicability, and a great regenerating potential, this injectable hydrogel
      promises as a treatment for myocardial infarction.

PMID- 19399851
TI  - A folded and functional synthetic PA1b: an interlocked entomotoxic miniprotein.
AB  - PA1b (Pea Albumin 1, subunit b) is a hydrophobic, 37-amino acid miniprotein
      isolated from pea seeds (Pivum sativum), crosslinked by three interlocked
      disulfide bridges, signature of the ICK (inhibitory cystine-knot) family. It acts
      as an entomotoxic factor against major insect pests in stored crops and
      vegetables, making it a promising bioinsecticide. Here we report an efficient and
      simple protocol for the production of large quantities of highly pure,
      biologically active synthetic PA1b. The features of PA1b oxidative refolding
      revealed the off-pathway products and competitive aggregation processes. The
      efficiency of the oxidative folding can be significantly improved by using
      hydrophobic alcoholic cosolvents and decreasing the temperature. The homogeneity
      of the synthetic oxidized PA1b was established by reversed-phase HPLC. The
      correct pairing of the three disulfide bridges, as well as the three-dimensional
      structure of synthetic PA1b was assessed by NMR. Synthetic PA1b binds to
      microsomal proteins from Sitophilus oryzae with a Kd of 8 nM, a figure quite
      similar to that determined for PA1b extracted from its natural source. Moreover,
      the synthetic miniprotein was as potent as the extracted one towards the
      sensitive strains of weevils. Our findings will open the way to the production of
      PA1b analogues by chemical means to an in-depth understanding of the PA1b
      mechanism of action.

PMID- 19399852
TI  - Specific labeling with potent radiolabels alters the uptake of cell-penetrating
      peptides.
AB  - Radiolabeled peptides play an important role in radiopharmacy not only as tumor
      markers but also as transport vectors. Therefore, cell-penetrating peptides (CPP)
      may serve as very effective delivery tools, as well. Recently, CPP based on the
      human hormone calcitonin (hCT) have been developed. Especially, branched hCT
      peptide sequences turned out to have highly efficient internalization capacities.
      Labeling these peptides with radionuclides would generate promising new tools for
      imaging and therapy applications in radiopharmacy. However, the influence of the
      metal complexation on the internalization capacity of CPP has not been elucidated
      yet in detail. In this study we quantified the uptake of Ga-DOTA modified hCT
      carrier peptides in HeLa cells by using atomic absorption spectroscopy (AAS) and
      compared the results to the uptake of fluorescently-labeled peptides.
      Interestingly, we measured different uptake rates depending on the attached
      label. Unexpectedly, modification with a Ga-DOTA complex can have tremendous
      effects on the uptake efficiency. The results of these studies support the need
      of detailed analysis of each carrier peptide/cargo construct, especially in the
      field of metal complex modified CPP.

PMID- 19399854
TI  - Cigarettes and amyotrophic lateral sclerosis: only smoke or also fire?

PMID- 19399855
TI  - Modification of polyurethane to reduce occlusion of enteral feeding tubes.
AB  - Feeding tubes are used to supply nutritional formula to immobilized patients. The
      most common cause for failure of enteral feeding tubes is their occlusion. The
      purpose of this study was to examine whether occlusion of enteral feeding tubes
      could be minimized using an additive. An open, intermittent enteral feeding
      system was simulated in the laboratory and data were collected over a period
      ranging from 2 to 6 days. Feeding formula was cycled through a feeding tube in
      either the presence or absence of simulated gastric acid in an effort to generate
      a reproducible occlusion. Pressures in the tube were measured frequently
      throughout these cycles. We observed pressure spikes with each cycle, but never a
      complete occlusion. Pressure spikes formed only when simulated gastric acid was
      mixed with the feeding solution. Large amounts of feeding formula adsorbed onto
      polyurethane (PU) surfaces in the presence of gastric acid. Also, this subtle
      change in surface chemistry significantly affected the number of pressure spikes
      observed. The maximum pressure required to maintain flow in the tube was reduced
      by about half from 2.0 psi to 0.8 psi when polyvinyl alcohol (PVA) was added. The
      addition of PVA to PU also reduced the contact angle from 83 degrees (untreated)
      to approximately 64 degrees in the presence of PVA. Furthermore, when formula was
      added to PU in the presence of PVA the thickness of the layer that remained on
      the surface was almost 10 times greater in controls than on PVA-treated surfaces.
      These results suggest that a treatment that increases the hydrophilicity of the
      feeding tube may help minimize clogging.

PMID- 19399856
TI  - Economic over-stimulation?

PMID- 19399857
TI  - Unabated increases in trial costs reflect evolving research milieu.

PMID- 19399858
TI  - Signal processing to evaluate parameters affecting SPE for multi-residue analysis
      of personal care products.
AB  - This paper discusses the development of a comprehensive method for the
      simultaneous analysis of personal care products (PCPs) based on SPE and GC-MS.
      The method was developed on 29 target compounds to represent PCPs belonging to
      different chemical classes: surfactants in detergents (alkyl benzenes),
      fragrances in cosmetics (nitro and polycyclic musks), antioxidants and
      preservatives (phenols), plasticizers (phthalates) displaying a wide range of
      volatility, polarity, water solubility. In addition to the conventional C(18)
      stationary phase, a surface modified styrene divinylbenzene polymeric phase
      (Strata X SPE cartridge) has been investigated as suitable for the simultaneous
      extraction of several PCPs with polar and non-polar characteristics. For both
      sorbents different solvent compositions and eluting conditions were tested and
      compared in order to achieve high extraction efficiency for as many sample
      components as possible. Comparison of the behavior of the two cartridges reveals
      that, overall, Strata-X provides better efficiency with extraction recovery
      higher than 70% for most of the PCPs investigated. The best results were obtained
      under the following operative conditions: an evaporation temperature of 40
      degrees C, elution on Strata-X cartridge using a volume of 15 mL of ethyl acetate
      (EA) as solvent and operating with slow flow rate (-10 KPa). In addition to the
      conventional method based on peak integration, a chemometric approach based on
      the computation of the experimental autocovariance function (EACVF(tot)) was
      applied to the complex GC-MS signal: the percentage recovery and information on
      peak abundance distribution can be evaluated for each procedure step. The PC
      based signal processing proved very helpful in assisting the development of the
      analytical procedure, since it saves labor and time and increases result
      reliability in handling GC complex signals.

PMID- 19399859
TI  - Simultaneous determination of 103 pesticide residues in tea samples by LC-MS/MS.
AB  - A simple and sensitive method was developed and validated for the simultaneous
      determination of 103 pesticide residues in tea by LC-MS/MS. For the analysis of
      the pesticide with polarity, thermal lability or low volatility, this LC-MS/MS
      method has an advantage over GC. In this work, residual pesticides were extracted
      from the tea sample with ACN and then purified using Carb-NH(2) SPE cartridges.
      Using the multiple reaction monitoring mode, the pesticides were quantified and
      identified by the most abundant and characteristic fragment ions. The recoveries
      obtained for each pesticide ranged between 65 and 114% at three spiked
      concentration levels. The intra-day precisions were lower than 19.6%. Good linear
      relationships were observed with the correlation coefficients r(2) >0.996 for all
      analytes. The established method was successfully applied to the determination of
      pesticide residues in real tea samples.

PMID- 19399860
TI  - Removal of endocrine-disrupting compounds from water using macroporous
      molecularly imprinted cryogels in a moving-bed reactor.
AB  - Highly efficient removal of endocrine-disrupting compounds (EDCs) such as 17beta
      estradiol (E2), 4-nonylphenol (NP) and atrazine from water was achieved using a
      novel macroporous adsorption medium. The medium consisted of a macroporous
      poly(vinyl alcohol) (PVA) cryogel with molecularly imprinted polymer (MIP)
      particles embedded in it. The MIP was prepared using E2, NP and atrazine as
      templates. The macroporous composite molecularly imprinted cryogels were formed
      inside the open-ended protective shells, known as Kaldnes carriers. These
      adsorbents (defined as Macroporous Gel Particles, MGPs) were evaluated on the
      removal of E2, NP and atrazine from water using different column configurations,
      namely column filled with the MGPs (packed-bed column) and in moving-bed reactors
      (defined here as moving-bed MGPs reactor). Complete binding (> 99%) of E2 from a
      spiked aqueous solution (1 mg/L) was achieved using E2-MIP/MGPs in a moving-bed
      MGPs reactor at the retention time in the reactor of 4 min, while only 77% was
      bound to the nonimprinted medium (NIP/MGPs). Similar results were also obtained
      for the adsorption medium imprinted with atrazine. All contaminants studied (E2,
      atrazine and NP) were effectively removed from water at low (environmentally
      relevant) concentrations by the respective adsorption medium.

PMID- 19399862
TI  - LC-MS of novel narcoepileptics and related substances.
AB  - Modafinil, adrafinil and their related substances were synthesized and analyzed
      by RP-LC with ESI-MS/MS. The ionization mode, polarity, cone voltage, and
      chromatographic conditions were evaluated. The optimum LC-MS conditions to obtain
      fragment ions indispensable for identification of the structures were described.
      The bulk drugs purity of modafinil and adrafinil was evaluated on Kromasil C(18)
      column with ACN/0.02 M ammonium acetate as mobile phase in gradient elution mode
      at 30 degrees C. The method was found to be suitable not only for monitoring the
      reactions during the process development but also for quality assurance of
      modafinil and adrafinil.

PMID- 19399863
TI  - Comparison of C18 silica bonded phases selectivity in micellar liquid
      chromatography.
AB  - The paper describes a new test designed in micellar LC (MLC) to compare the
      commercial C18 stationary phase properties. This test provides the total
      hydrophobicity, hydrophilicity, steric selectivity, hydrogen bonding, and ion
      exchange capacity properties calculation of the ODS stationary phases. Both the
      test compounds and chromatographic separation conditions choice for column
      characterization in MLC are detailed. The chromatographic performance of several
      stationary phases that are used in MLC was evaluated with specific
      chromatographic test comprising nine test compounds, possessing different physico
      chemical properties, which were injected on different supports with two micellar
      mobile phases: one at pH 7.0 (0.075 mol/L SDS and 1.5% v/v 1-pentanol), and other
      at pH 2.7 (0.075 mol/L SDS and 1.5% v/v 1-pentanol adjusted to pH by TFA).
      Fundamental column chromatographic properties were obtained under these
      conditions and were treated by hierarchical cluster analysis. From the results of
      cluster analysis, two closely related groups of columns are distinguished, and it
      was shown that the chosen column characteristic parameters allow characterizing
      both sorbent and micellar chromatographic system properties. Eleven columns were
      analyzed by this test, which allows a comparison of columns with the aim of the
      selection of suitable and analogous column for the analysis with MLC.

PMID- 19399864
TI  - Quantitation of imidazo[1,2-a]quinoxaline derivatives in human and rat plasma
      using LC/ESI-MS.
AB  - Since several years, our group developed quinoxalinic compounds. Among the
      synthesized compounds, in the imidazo[1,2-a]quinoxaline series, EAPB0203 has
      shown interesting activities both on melanoma and lymphoma. The structure of
      EAPB0203 has been modulated and a new compound, EAPB0503, exhibits an in vitro
      cytotoxic activity on melanoma cancer cell line 7-9 times higher than EAPB0203.
      We validated an LC/ESI-MS method to simultaneously quantify EAPB0503 and its
      metabolite EAPB0603 in human and rat plasma. Chromatography was performed on a C8
      Zorbax eclipse XDB column with a mobile phase consisting of acetronitrile and
      formate buffer gradient elution. LC-MS data were acquired in SIM mode at m/z 305,
      291, and 303 for EAPB0503, EAPB0603, and the internal standard, respectively. The
      drug/internal standard peak area ratios were linked via quadratic relationships
      to concentrations (low range: 5-300 microg/L, high range: 100-1000 microg/L). The
      method is precise (precision, < or = 14%) and accurate (recovery, 92-113%). Mean
      extraction efficiencies, > 72% for each analyte, were obtained. The lower LOQs
      were 5 microg/L. This highly specific and sensitive method was successfully used
      to investigate plasma concentrations of EAPB0503 and EAPB0603 in a
      pharmacokinetic study carried out in rat and would also be useful in clinical
      trials at a later stage.

PMID- 19399865
TI  - Editor Luigi Mondello speaks with Professor Keith Bartle. Interview by Luigi
      Mondello.

PMID- 19399866
TI  - Smoking and risk for amyotrophic lateral sclerosis: analysis of the EPIC cohort.
AB  - OBJECTIVE: Cigarette smoking has been reported as "probable" risk factor for
      Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of
      aetiology. The extensive longitudinal data of the European Prospective
      Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific
      mortality rates from ALS and the role of cigarette smoking on the risk of dying
      from ALS. METHODS: A total of 517,890 healthy subjects were included, resulting
      in 4,591,325 person-years. ALS cases were ascertained through death certificates.
      Cox hazard models were built to investigate the role of smoking on the risk of
      ALS, using packs/years and smoking duration to study dose-response. RESULTS: A
      total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69
      per 100,000/year. Current smokers at recruitment had an almost two-fold increased
      risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14),
      while former smokers at the time of enrollment had a 50% increased risk (HR =
      1.48, 95% C.I. 0.94-2.32). The number of years spent smoking increased the risk
      of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a
      two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I.
      1.33-3.53). Conversely, the number of years since quitting smoking was associated
      with a decreased risk of ALS compared with continuing smoking. INTERPRETATION:
      These results strongly support the hypothesis of a role of cigarette smoking in
      aetiology of ALS. We hypothesize that this could occur through lipid peroxidation
      via formaldehyde exposure.

PMID- 19399867
TI  - Predicting the unpredictable.

PMID- 19399869
TI  - Creatine metabolism in combined methylmalonic aciduria and homocystinuria disease
      revisited.

PMID- 19399871
TI  - To test or not to test children with developmental disorders.

PMID- 19399872
TI  - Metabolic evaluation in neurodevelopmental disabilities.

PMID- 19399873
TI  - Initiating therapy in Parkinson's disease.

PMID- 19399874
TI  - Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models.
AB  - OBJECTIVE: Conventional anticonvulsants reduce neuronal excitability through
      effects on ion channels and synaptic function. Anticonvulsant mechanisms of the
      ketogenic diet remain incompletely understood. Because carbohydrates are
      restricted in patients on the ketogenic diet, we evaluated the effects of
      limiting carbohydrate availability by reducing glycolysis using the glycolytic
      inhibitor 2-deoxy-D-glucose (2DG) in experimental models of seizures and
      epilepsy. METHODS: Acute anticonvulsant actions of 2DG were assessed in vitro in
      rat hippocampal slices perfused with 7.5mM [K(+)](o), 4-aminopyridine, or
      bicuculline, and in vivo against seizures evoked by 6 Hz stimulation in mice,
      audiogenic stimulation in Fring's mice, and maximal electroshock and subcutaneous
      pentylenetetrazol (Metrazol) in rats. Chronic antiepileptic effects of 2DG were
      evaluated in rats kindled from olfactory bulb or perforant path. RESULTS: 2DG
      (10mM) reduced interictal epileptiform bursts induced by 7.5mM [K(+)](o), 4
      aminopyridine, and bicuculline, and electrographic seizures induced by high
      [K(+)](o) in CA3 of hippocampus. 2DG reduced seizures evoked by 6 Hz stimulation
      in mice (effective dose [ED]50 = 79.7 mg/kg) and audiogenic stimulation in
      Fring's mice (ED50 = 206.4 mg/kg). 2DG exerted chronic antiepileptic action by
      increasing afterdischarge thresholds in perforant path (but not olfactory bulb)
      kindling and caused a twofold slowing in progression of kindled seizures at both
      stimulation sites. 2DG did not protect against maximal electroshock or Metrazol
      seizures. INTERPRETATION: The glycolytic inhibitor 2DG exerts acute
      anticonvulsant and chronic antiepileptic actions, and has a novel pattern of
      effectiveness in preclinical screening models. These results identify metabolic
      regulation as a potential therapeutic target for seizure suppression and
      modification of epileptogenesis.

PMID- 19399876
TI  - Mesencephalic astrocyte-derived neurotrophic factor reduces ischemic brain injury
      and promotes behavioral recovery in rats.
AB  - Mesencephalic astrocyte-derived neurotrophic factor (MANF), also known as
      arginine-rich, mutated in early stage of tumors (ARMET), is a secreted protein
      that reduces endoplasmic reticulum (ER) stress. Previous studies have shown that
      MANF mRNA expression and protein levels are increased in the cerebral cortex
      after brain ischemia, a condition that induces ER stress. The function of MANF
      during brain ischemia is still not known. The purpose of this study was to
      examine the protective effect of MANF after ischemic brain injury. Recombinant
      human MANF was administrated locally to the cerebral cortex before a 60-min
      middle cerebral artery occlusion (MCAo) in adult rats. Triphenyltetrazolium
      chloride (TTC) staining indicated that pretreatment with MANF significantly
      reduced the volume of infarction at 2 days after MCAo. MANF also attenuated TUNEL
      labeling, a marker of cell necrosis/apoptosis, in the ischemic cortex. Animals
      receiving MANF pretreatment demonstrated a decrease in body asymmetry and
      neurological score as well as an increase in locomotor activity after MCAo. Taken
      together, these data suggest that MANF has neuroprotective effects against
      cerebral ischemia, possibly through the inhibition of cell necrosis/apoptosis in
      cerebral cortex.

PMID- 19399877
TI  - Effect of levodopa priming on dopamine neuron transplant efficacy and induction
      of abnormal involuntary movements in parkinsonian rats.
AB  - Clinical trials of neural grafting for Parkinson's disease (PD) have produced
      variable, but overall disappointing, results. One particular disappointment has
      been the development of aberrant motor complications following dopamine (DA)
      neuron grafting. Despite a lack of consistent benefit, the utility of dopamine
      neuron replacement remains supported by clinical and basic data. In a continued
      effort to elucidate factors that might improve this therapy, we used a
      parkinsonian rat model to examine whether pregraft chronic levodopa affected
      graft efficacy and/or graft-induced dyskinesia (GID) induction. Indeed, all
      grafted PD patients to date have had a pregraft history of long-term levodopa. It
      is well established that long-term levodopa results in a plethora of long-lasting
      neurochemical alterations and genomic changes indicative of altered structural
      and synaptic plasticity. Thus, therapeutic dopamine terminal replacement in a
      striatal environment complicated by such changes could be expected to lead to
      abnormal or inappropriate connections between graft and host brain and to
      contribute to suboptimal efficacy and/or postgraft GID behaviors. To investigate
      the effect of pregraft levodopa, one group of parkinsonian rats received levodopa
      for 4 weeks prior to grafting. A second levodopa-naive group was grafted, and the
      grafts were allowed to mature for 9 weeks prior to introducing chronic levodopa.
      We report here that, in parkinsonian rats, preexposure to chronic levodopa
      significantly reduces behavioral and neurochemical efficacy of embryonic dopamine
      grafts. Furthermore, dopamine terminal replacement prior to introduction of
      chronic levodopa is highly effective at preventing development of levodopa
      induced dyskinesias, and GID-like behaviors occur regardless of pregraft levodopa
      status.

PMID- 19399878
TI  - Hyperbaric oxygen therapy protects the liver from apoptosis caused by ischemia
      reperfusion injury in rats.
AB  - PURPOSE: : The present paper aimed to investigate the role of hyperbaric oxygen
      treatment (HBO) and the apoptosis in rat liver ischemia-reperfusion injury (IRI).
      METHODS: : Thirty-seven male Wistar rats were subjected to 30 minutes of hepatic
      ischemia and 30 minutes of reperfusion and randomly distributed into six groups:
      G-I/R (n = 8), control without HBO; G-HBO/I (n = 8), HBO only during the ischemia
      period; G-HBO/R (n = 8), HBO only during the reperfusion period; G-HBO-I/R (n =
      8), HBO during both the ischemia and reperfusion periods; G-Sh (n = 3), HBO
      without ischemia or reperfusion as sham group; G-C (n = 2) for control of current
      apoptosis expression on the normal liver tissue. HBO was carried out using a
      transparent, cylindrical acrylic chamber with a pressure of 2.0 ATA. Hepatic
      samples were stained for caspase-3 cleavage. RESULTS: : Apoptotic cells were
      identified in all groups. In the hepatic specimens of animals HBO-treated during
      ischemia (GHBO-I), there was a significant decrease (P < 0.001) in the number of
      cells undergoing apoptosis (1.62 +/- 0.91). The apoptotic index showed no
      significant difference in the animals HBO-treated during ischemia/reperfusion
      (5.75 +/- 1.28) compared with the G-I/R (3.5 +/- 0.75), which had no HBO
      treatment. The apoptosis index (11.25 +/- 1.90) was significantly higher (P <
      0.01) in HBO-treated animals during the reperfusion period when compared with any
      of the other groups. CONCLUSION: : A favorable effect was obtained when
      hyperbaric oxygen was administered early during ischemia. The hyperbaric oxygen
      in later periods of reperfusion was associated with a more severe apoptosis
      index. (c) 2009 Wiley-Liss, Inc. Microsurgery 2009.

PMID- 19399880
TI  - Perineal and posterior vaginal wall reconstruction with superior and inferior
      gluteal artery perforator flaps.
AB  - Perineal and posterior vaginal wall reconstruction following abdominoperineal and
      local cancer resection entails replacement of volume between the perineum and
      sacrum and restoration of a functional vagina. Ideal local reconstructive options
      include those which avoid functional muscle sacrifice, do not interfere with
      colostomy formation, and avoid the use of irradiated tissue. In avoiding the
      donor site morbidity of other options, we describe a fasciocutaneous option for
      the reconstruction of the perineum and posterior vaginal wall. We present our
      technique of superior and inferior gluteal artery perforator (SGAP or IGAP) flaps
      to reconstruct such defects. Fourteen patients between 2004 and 2008 underwent 11
      SGAP and three IGAP flaps. There were no flap failures or partial flap losses and
      no postoperative hernias. All female patients reported resumption of sexual
      intercourse following this procedure. Our experience in both the immediate and
      delayed setting is that this technique produces a good functional outcome with
      low donor-site morbidity.

PMID- 19399881
TI  - Postoperative monitoring of free vascularized bone grafts in reconstruction of
      bone defects.
AB  - Vascularized bone transfer is increasingly recognized as a very useful and
      versatile technique for reconstructing large bone defects. It is especially
      indicated in patients with challenging conditions, such as nonunions,
      postoncologic resections, severe trauma, and congenital defects. With increasing
      experience of reconstructive surgeons, improved microsurgical techniques, and
      more enhanced flaps, the failure rate of free flaps has been reduced in the last
      decades. Especially, the early-postoperative period is decisive in the outcome of
      surgery. Several techniques have been described for monitoring the postoperative
      viability of microsurgical free vascularized graft, and their sensitivity and
      reliability continues to be the object of animal experiments and clinical trials.
      The qualities of an optimal monitoring device should be objective, continuous,
      noninvasive, safe, reproducible, easily managed, and interpretable for the
      nursing staff, inexpensive, and a clear indicator of changes in arterial and
      venous circulation. Presently, no one neither fulfills all of the criteria
      completely nor is uniformly accepted. In this article, relative advantages and
      disadvantages of these various postoperative monitoring techniques are discussed.

PMID- 19399879
TI  - Clinical-neuroimaging characteristics of dysexecutive mild cognitive impairment.
AB  - OBJECTIVE: Subgroups of mild cognitive impairment (MCI) have been proposed, but
      few studies have investigated the nonamnestic, single-domain subgroup of MCI. The
      goal of the study was to compare clinical and neuroimaging characteristics of two
      single-domain MCI subgroups: amnestic MCI and dysexecutive MCI. METHODS: We
      compared the cognitive, functional, behavioral, and brain imaging characteristics
      of patients with amnestic MCI (n = 26), patients with dysexecutive MCI (n = 32),
      and age- and education-matched control subjects (n = 36) using analysis of
      variance and chi(2) tests. We used voxel-based morphometry to examine group
      differences in brain magnetic resonance imaging atrophy patterns. RESULTS:
      Patients with dysexecutive MCI had significantly lower scores on the majority of
      executive function tests, increased behavioral symptoms, and left prefrontal
      cortex atrophy on magnetic resonance imaging when compared with control subjects.
      In contrast, patients with amnestic MCI had significantly lower scores on tests
      of memory and a pattern of atrophy including bilateral hippocampi and entorhinal
      cortex, right inferior parietal cortex, and posterior cingulate gyrus when
      compared with control subjects. INTERPRETATION: Overall, the clinical and
      neuroimaging findings provide support for two distinct single-domain subgroups of
      MCI, one involving executive function and the other involving memory. The brain
      imaging differences suggest that the two MCI subgroups have distinct patterns of
      brain atrophy.

PMID- 19399882
TI  - Is the recipient vein really the main concern? A cohort study of head and neck
      reconstruction.
AB  - The aim of this study was to verify the role of the venous drainage system in the
      pathogenesis of complications in microsurgical head and neck reconstruction. In a
      nonrandomized cohort study, 52 consecutive cases of complex head and neck
      microsurgical reconstruction were evaluated. The patients were divided in two
      groups based on the treatment: the deep (DVDG; n = 30) and superficial (SVDG; n =
      22) venous drainage groups. The complications evaluated included vascular
      obstruction with partial or total loss of the microsurgical flap, inadequate
      healing (fistulas or suture dehiscence), and infections. The arterial anastomotic
      site, neoplastic recurrence, use of medications and neoadjuvant radiotherapy,
      flap selection, tumor histology, smoking/alcoholism, and systemic diseases had no
      effect on postoperative complications, while the venous component influenced the
      overall complication rate (chi-square test, P = 0.006). A protective effect was
      achieved in the DVDG when the overall complication rate was considered--relative
      risk (RR) 0.65, 95% confidence interval (CI) 0.45-0.94. The recipient vein should
      be the surgeon's main concern as it influenced the outcomes of patients
      undergoing complex microsurgical head and neck reconstruction. A protective
      effect was observed when the internal jugular vein drainage system was used for
      this purpose.

PMID- 19399883
TI  - A new protocol for complete phalloplasty with free sensate and prelaminated
      osteofasciocutaneous flaps: experience in 37 patients.
AB  - BACKGROUND: Herein, we present our latest protocol of following three operative
      stages for complete phalloplasty, applied in 37 female-to-male transsexuals:
      first, mastectomy, ovariohysterectomy, urethral lengthening, vaginectomy,
      colpocleisis, and neourethra prelamination; second, neophallus creation with free
      sensate osteofasciocutaneous fibula (n = 31) or radial forearm (n = 6) flap; and
      third, urethral connection, neoscrotum formation, and testicle prosthesis
      implantation. RESULTS: Occasionally, wound healing disturbance and slight
      asymmetry of the breasts was observed, as well as colpocleisis revision needed.
      Partial flap necrosis took place in 6 patients, while 12 presented urethral
      stricture and 6 a fistula. Despite inferior neophallus sensibility, patients
      whose neophallus was created using fibula flap experienced better sexual
      intercourse. However, overall patients' satisfaction was superior. CONCLUSIONS:
      The applied protocol demonstrates the effectiveness of such a multistage and
      interdisciplinary approach for female-to-male transsexuals, offering an essential
      improvement of their quality of life, concerning their successful integration
      into the reassigned gender position in the society.

PMID- 19399884
TI  - Withdrawal of figure 2 from McNaught and Olanow's article, "Proteasome inhibitor
      induced model of Parkinson's disease" (Ann Neurol 2006;60:243-247).

PMID- 19399888
TI  - Preventing infective complications following leech therapy: is practice keeping
      pace with current research?
AB  - BACKGROUND: Despite several publications strongly advocating prophylactic
      antibiotics during leech therapy, and recent primary articles shedding new light
      on the microbiota of leeches, many units either do not use antibiotic
      prophylaxis, or are continuing to use ineffective agents. METHODS: A 5-year
      follow-up of plastic surgery units in the United Kingdom and the Republic of
      Ireland was conducted in 2007 to ascertain current practice regarding the use of
      prophylactic antibiotics with leech therapy. A comprehensive literature search
      investigated primary research articles regarding the microbiota of leeches to
      update the reconstructive surgery community. RESULTS: Despite published evidence
      to support the use of prophylactic antibiotics during leech therapy, 24% of units
      do not use antibiotic prophylaxis and 57% of those using antibiotics are using
      potentially ineffective agents. Advanced molecular genetic techniques, which
      allow accurate characterization of both culturable and non-culturable microbiota
      of the leech digestive tract, show a wider diversity than at first thought, with
      variable antibiotic resistance profiles. CONCLUSIONS: Despite infection due to
      leech therapy being a well known and relatively common complication, many units
      are not using appropriate antibiotic prophylaxis.

PMID- 19399887
TI  - Vascular endothelial growth factor gene transfer for diabetic polyneuropathy: a
      randomized, double-blinded trial.
AB  - OBJECTIVE: Randomized, blinded trial of intramuscular gene transfer using plasmid
      vascular endothelial growth factor (VEGF) to treat diabetic polyneuropathy.
      METHODS: Diabetic patients with polyneuropathy were randomized to receive a VEGF
      to-placebo ratio of 3:1. Three sets of injections were given at eight
      standardized sites adjacent to the sciatic, peroneal, and tibial nerves of one
      leg. Primary outcomes were change in symptom score at 6 months and a prespecified
      overall clinical and electrophysiological improvement score. Secondary outcomes
      were differences in symptoms, examination scores, visual analog pain scale, nerve
      conduction, and quantitative sensory testing. RESULTS: Thirty-nine patients
      received plasmid VEGF and 11 received placebo. Mean symptom score improved in
      both legs at 6 months, favoring VEGF over placebo (-1.2 +/- 0.5 vs -0.9 +/- 0.5;
      p < 0.01 after adjustment for change in the untreated leg) and compared with the
      untreated leg (-0.7 +/- 0.5; p = 0.02). The region of sensory loss and visual
      analog pain scale improved in the treated group (-1.5 vs -0.5; p = 0.01). Twelve
      of 39 VEGF versus 2 of 11 placebo patients met criterion for overall improvement.
      Other measures including nerve conduction potentials did not improve. There were
      84 adverse events in VEGF patients, and 22 were serious; there were 51 events in
      placebo patients, and 2 were serious. INTERPRETATION: Intramuscular plasmid VEGF
      gene transfer improved diabetic neuropathic symptoms, meeting primary end-point
      criteria for efficacy but not affecting most secondary measures. Treatment was
      associated with more serious adverse events that did not reach statistical
      significance. These results are not conclusive but may justify further clinical
      study.

PMID- 19399889
TI  - Prognostic value of brain diffusion-weighted imaging after cardiac arrest.
AB  - OBJECTIVE: Outcome prediction is challenging in comatose postcardiac arrest
      survivors. We assessed the feasibility and prognostic utility of brain diffusion
      weighted magnetic resonance imaging (DWI) during the first week. METHODS:
      Consecutive comatose postcardiac arrest patients were prospectively enrolled. AWI
      data of patients who met predefined specific prognostic criteria were used to
      determine distinguishing apparent diffusion coefficient (ADC) thresholds. Group 1
      criteria were death at 6 months and absent motor response or absent pupillary
      reflexes or bilateral absent cortical responses at 72 hours or vegetative at 1
      month. Group 2 criterion was survival at 6 months with a Glasgow Outcome Scale
      score of 4 or 5 (group 2A) or 3 (group 2B). The percentage of voxels below
      different ADC thresholds was calculated at 50 x 10(-6) mm(2)/sec intervals.
      RESULTS: Overall, 86% of patients underwent DWI. Fifty-one patients with 62 brain
      DWIs were included. Forty patients met the specific prognostic criteria. The
      percentage of brain volume with an ADC value less than 650 to 700 x 10(
      6)mm(2)/sec best differentiated between Group 1 and Groups 2A and 2B combined (p
      < 0.001), whereas the 400 to 450 x 10(-6)mm(2)/sec threshold best differentiated
      between Groups 2A and 2B (p = 0.003). The ideal time window for prognostication
      using DWI was between 49 and 108 hours after the arrest. When comparing DWI in
      this time window with the 72-hour neurological examination, DWI improved the
      sensitivity for predicting poor outcome by 38% while maintaining 100% specificity
      (p = 0.021). INTERPRETATION: Quantitative DWI in comatose postcardiac arrest
      survivors holds promise as a prognostic adjunct.

PMID- 19399890
TI  - Supermicrosurgical lymphaticovenular anastomosis and lymphaticovenous
      implantation for treatment of unilateral lower extremity lymphedema.
AB  - Recent supermicrosurgical techniques have developed the possibility for vascular
      anastomosis of smaller vessels and it is now safe and sound to perform precise
      anastomoses between lymphatics and venules. Reported here is the 2 years
      experience on supermicrosurgical lymphaticovenular anastomosis and/or
      lymphaticovenous implantation combined with a nonoperative physical therapy for
      treatment of lower extremity lymphedema. Microlymphatic surgery was performed in
      42 patients with unilateral lower extremity lymphedema. Thirty patients were
      women and 12 were men with a mean age of 34. Lymphaticovenular anastomoses were
      performed in 37 patients with an average of 2.5 anastomoses per patient, and
      lymphaticovenous implantations were made in 36 patients with an average of 2.4
      implantations per patient. The lymphatics that were larger than 0.3 mm were
      anastomosed to venules with supermicrosurgical technique. Lymphaticovenous
      implantation technique was used for thinner lymphatics in a particular incision.
      Postoperatively, 18 patients used continuous compressive garments, 9 patients
      used garments but discontinued after 6 months, and no compression was used in 9
      patients. The results of surgery were assessed both clinically with volume
      measurements and by lymphoscintigraphy and were classified as good, moderate, or
      ineffective. The mean decrease in the volume of the edema was 59.3% at an average
      follow-up of 11.8 months. Six outcomes were classified as ineffective, eight
      outcomes as moderate, and 28 outcomes as good. Supermicrosurgical
      lymphaticovenular anastomosis and/or lymphaticovenous implantation seems to be
      highly beneficial, especially in the early stages of peripheral lymphedema and
      may be offered as the treatment of choice in selected patients.

PMID- 19399885
TI  - Stem cells for ischemic brain injury: a critical review.
AB  - No effective therapy is currently available to promote recovery following
      ischemic stroke. Stem cells have been proposed as a potential source of new cells
      to replace those lost due to central nervous system injury, as well as a source
      of trophic molecules to minimize damage and promote recovery. We undertook a
      detailed review of data from recent basic science and preclinical studies to
      investigate the potential application of endogenous and exogenous stem cell
      therapies for treatment of cerebral ischemia. To date, spontaneous endogenous
      neurogenesis has been observed in response to ischemic injury, and can be
      enhanced via infusion of appropriate cytokines. Exogenous stem cells from
      multiple sources can generate neural cells that survive and form synaptic
      connections after transplantation in the stroke-injured brain. Stem cells from
      multiple sources cells also exhibit neuroprotective properties that may
      ameliorate stroke deficits. In many cases, functional benefits observed are
      likely independent of neural differentiation, although the exact mechanisms
      remain poorly understood. Future studies of neuroregeneration will require the
      demonstration of function in endogenously born neurons following focal ischemia.
      Further, methods are currently lacking to demonstrate definitively the
      therapeutic effect of newly introduced neural cells. Increased plasticity
      following stroke may facilitate the functional integration of new neurons, but
      the loss of appropriate guidance cues and supporting architecture in the infarct
      cavity will likely impede the restoration of lost circuitry. Thus careful
      investigation of the mechanisms underlying trophic benefits will be essential.
      Evidence to date suggests that continued development of stem cell therapies may
      ultimately lead to viable treatment options for ischemic brain injury.

PMID- 19399891
TI  - Embryonic substantia nigra grafts in the mesencephalon send neurites to the host
      striatum in non-human primate after overexpression of GDNF.
AB  - In spite of partial success in treating Parkinson's disease by using ectopically
      placed grafts of dopamine-producing cells, restoration of the original
      neuroanatomical circuits, if possible, might work better. Previous evidence of
      normal anatomic projections from ventral mesencephalic (VM) grafts placed in the
      substantia nigra (SN) has been limited to neonatal rodents and double grafting or
      bridging procedures. This study attempted to determine whether injection of a
      potent growth-promoting factor, glial cell line-derived neurotrophic factor
      (GDNF), into the target regions or placement of fetal striatal co-grafts in the
      nigrostriatal pathway might elicit neuritic outgrowth to the caudate nucleus.
      Four adult St. Kitts green monkeys received embryonic VM grafts into the rostral
      mesencephalon near the host SN, and injections of adeno-associated virus 2
      (AAV2)/GDNF or equine infectious anemia virus (EIAV)/GDNF into the caudate. Three
      adult monkeys were co-grafted with fetal VM tissue near the SN and fetal striatal
      grafts (STR) 2.5 mm rostral in the nigrostriatal pathway. Before sacrifice, the
      striatal target regions were injected with the retrograde tracer Fluoro-Gold
      (FG). FG label was found in tyrosine hydroxylase-labeled neurons in VM grafts in
      the SN of only those monkeys that received AAV2/GDNF vector injections into the
      ipsilateral striatum. All monkeys showed FG labeling in the host SN when FG
      labeling was injected on the same side. These data show that grafted dopaminergic
      neurons can extend neurites to a distant target releasing an elevated
      concentration of GDNF, and suggest that grafted neurons can be placed into
      appropriate loci for potential tract reconstruction.

PMID- 19399892
TI  - Pattern of long-term sensorimotor recovery following intrastriatal and--accumbens
      DA micrografts in a rat model of Parkinson's disease.
AB  - The functional restorative capacity of fetal dopaminergic (DA) transplants is
      governed by a number of critical parameters including graft location, survival of
      DA neurons, and transplantation technique. In addition, there is an ongoing
      controversy whether "too much" or "too little" survival of DA neurons is
      responsible for the incomplete functional recovery observed in some transplanted
      Parkinson's disease (PD) patients. Here we investigated two implantation sites,
      the nucleus accumbens (NAc) and the caudate-putamen unit (CPU), and two different
      graft distributions within the CPU, i.e., two 0.75 microL deposits (CPU-2) versus
      six 0.25 microL deposits (CPU-6) in a rat model of PD. Grafts were derived from
      E14 rat ventral mesencephalon and the long-term functional outcome was evaluated
      with a wide range of complex-sensorimotor behavioral tests. The data show that
      forelimb stepping, balancing behavior, and skilled forelimb reaching behavior was
      more restored in CPU-6-grafted animals as compared to CPU-2 animals, although the
      number surviving dopaminergic neurons and dopamine release were similar in the
      two groups. Furthermore, a correlation analysis revealed a number of inverse
      relationships between the rate of DA neuron survival and sensorimotor
      performances, e.g., for skilled forelimb use. DA grafts placed into the NAc
      induced a partial recovery in drug-induced rotation tests but failed to restore
      any of the other sensorimotor behaviors tested. Taken together, these data have
      important implications both for a better understanding of the complex functional
      graft-host interactions as well as for the further optimization of clinical
      neural transplantation strategies in neurodegenerative diseases.

PMID- 19399894
TI  - Beneficial effects of antioxidant-enriched diet for tyrosine hydroxylase-positive
      neurons in ventral mesencephalic tissue in oculo grafts.
AB  - Supplementation of antioxidants to the diet has been proved to be beneficial in
      aging and after brain injury. Furthermore, it has been postulated that the locus
      coeruleus promotes survival of dopamine neurons. Thus, this study was performed
      to elucidate the effects of a blueberry-enriched diet on fetal ventral
      mesencephalic tissue in the presence or absence of locus coeruleus utilizing the
      in oculo grafting method. Sprague-Dawley rats were given control diet or diet
      supplemented with 2% blueberries, and solid tissue pieces of fetal locus
      coeruleus and ventral mesencephalon were implanted as single and co-grafts. The
      results revealed that the presence of locus coeruleus tissue or the addition of
      blueberries enhanced the survival of ventral mesencephalic tyrosine hydroxylase
      (TH)-positive neurons, whereas no additive effects were observed for the two
      treatments. The density of TH-positive nerve fibers in ventral mesencephalic
      tissue was significantly elevated when it was attached to the locus coeruleus or
      by blueberry treatment, whereas the innervation of dopamine-beta-hydroxylase
      positive nerve fibers was not altered. The presence of locus coeruleus tissue or
      bluberry supplementation reduced the number of Iba-1-positive microglia in the
      ventral mesencephalic portion of single and co-grafts, respectively, whereas
      almost no OX6 immunoreactivity was found. Furthermore, neither the attachment of
      ventral mesencephalic tissue nor the addition of blueberries improved the
      survival of TH-positive neurons in the locus coerulean grafts. To conclude, locus
      coeruleus and blueberries are beneficial for the survival of fetal ventral
      mesencephalic tissue, findings that could be useful when grafting tissue in
      Parkinson's disease.

PMID- 19399893
TI  - Combined extrinsic and intrinsic manipulations exert complementary neuronal
      enrichment in embryonic rat neural precursor cultures: an in vitro and in vivo
      analysis.
AB  - Numerous central nervous system (CNS) disorders share a common pathology in
      dysregulation of gamma-aminobutyric acid (GABA) inhibitory signaling.
      Transplantation of GABA-releasing cells at the site of disinhibition holds
      promise for alleviating disease symptoms with fewer side effects than traditional
      drug therapies. We manipulated fibroblast growth factor (FGF)-2 deprivation and
      mammalian achaete-scute homolog (MASH)1 transcription factor levels in an attempt
      to amplify the default GABAergic neuronal fate in cultured rat embryonic neural
      precursor cells (NPCs) for use in transplantation studies. Naive and MASH1
      lentivirus-transduced NPCs were maintained in FGF-2 or deprived of FGF-2 for
      varying lengths of time. Immunostaining and quantitative analysis showed that
      GABA- and beta-III-tubulin-immunoreactive cells generally decreased through
      successive passages, suggesting a loss of neurogenic potential in rat
      neurospheres expanded in vitro. However, FGF-2 deprivation resulted in a small,
      but significantly increased population of GABAergic cells derived from passaged
      neurospheres. In contrast to naive and GFP lentivirus-transduced clones, MASH1
      transduction resulted in increased bromodeoxyuridine (BrdU) incorporation and
      clonal colony size. Western blotting showed that MASH1 overexpression and FGF-2
      deprivation additively increased beta-III-tubulin and decreased cyclic nucleotide
      phosphodiesterase (CNPase) expression, whereas FGF-2 deprivation alone attenuated
      glial fibrillary acidic protein (GFAP) expression. These results suggest that low
      FGF-2 signaling and MASH1 activity can operate in concert to enrich NPC cultures
      for a GABA neuronal phenotype. When transplanted into the adult rat spinal cord,
      this combination also yielded GABAergic neurons. These findings indicate that,
      even for successful utilization of the default GABAergic neuronal precursor fate,
      a combination of both extrinsic and intrinsic manipulations will likely be
      necessary to realize the full potential of NSC grafts in restoring function.

PMID- 19399895
TI  - The dynamics of long-term transgene expression in engrafted neural stem cells.
AB  - To assess the dynamics and confounding variables that influence transgene
      expression in neural stem cells (NSCs), we generated distinct NSC clones from the
      same pool of cells, carrying the same reporter gene transcribed from the same
      promoter, transduced by the same retroviral vector, and transplanted similarly at
      the same differentiation state, at the same time and location, into the brains of
      newborn mouse littermates, and monitored in parallel for over a year in vivo
      (without immunosuppression). Therefore, the sole variables were transgene
      chromosomal insertion site and copy number. We then adapted and optimized a
      technique that tests, at the single cell level, persistence of stem cell-mediated
      transgene expression in vivo based on correlating the presence of the transgene
      in a given NSC's nucleus (by fluorescence in situ hybridization [FISH]) with the
      frequency of that transgene's product within the same cell (by combined
      immunohistochemistry [IHC]). Under the above-stated conditions, insertion site is
      likely the most contributory variable dictating transgene downregulation in an
      NSC after 3 months in vivo. We also observed that this obstacle could be
      effectively and safely counteracted by simple serial infections (as few as three)
      inserting redundant copies of the transgene into the prospective donor NSC. (The
      preservation of normal growth control mechanisms and an absence of tumorigenic
      potential can be readily screened and ensured ex vivo prior to transplantation.)
      The combined FISH/IHC strategy employed here for monitoring the dynamics of
      transgene expression at the single cell level in vivo may be used for other types
      of therapeutic and housekeeping genes in endogenous and exogenous stem cells of
      many organs and lineages.

PMID- 19399896
TI  - Intravenous administration of human umbilical cord blood cells in an animal model
      of MPS III B.
AB  - Sanfilippo syndrome type B (MPS III B) is caused by a deficiency of alpha-N
      acetylglucosaminidase enzyme (Naglu), leading to accumulation of heparan sulfate
      (HS), a glycosaminoglycan (GAG), within lysosomes and to eventual progressive
      cerebral and systemic multiple organ abnormalities. Treatment of MPS patients is
      mainly supportive and enzyme replacement cell therapy shows promise for treating
      this disease. One new approach for potential treatment of MPS III B is human
      umbilical cord blood (hUCB) cell transplantation. Recently, we demonstrated that
      administration of hUCB cells into the cerebral ventricle of presymptomatic Naglu
      mice had a beneficial effect, probably due to enzyme delivery into the enzyme
      deficient mutant mice. However, administration of these cells into the systemic
      circulation of mutant mice could be more advantageous and may lead to new
      strategies of enzyme replacement for Sanfilippo. The aim of this study was to
      determine the effect of intravenous administration of hUCB cells into a mouse
      model of Sanfilippo Syndrome type B. The major findings in our study were that
      hUCB cell administration improved behavioral outcomes (decreased
      hyper/stereotypical activity and improved cognitive function). Cells widely
      distribute within and outside the CNS and intraparenchymally migrate.
      Administered cells have an antiinflammatory effect (Th2-associated cytokines) in
      the brain and reduce heparan sulfate accumulation in the liver and spleen. Our
      results demonstrate the advantages of intravenously administering hUCB cells into
      a mouse model of Sanfilippo Syndrome type B, the advantages probably a result of
      Naglu delivery to enzyme-deficient organs.

PMID- 19399898
TI  - Strategic aspects of spermatogenesis and the maturation of spermatozoa.
      Introduction.

PMID- 19399900
TI  - Celebrating neural repair.

PMID- 19399901
TI  - Development of vaccination approaches for the treatment of neurological diseases.
AB  - Several progressive neurodegenerative diseases share a common pathology: the
      accumulation of misfolded proteins within cells or neuropil of the brain.
      Characteristically, these misfolded proteins form organized beta-sheet-containing
      assemblies that have optical and biochemical properties of amyloid. Thus, the
      brain amyloidoses, Alzheimer's disease (AD), Parkinson's disease, and the
      prionoses or transmissible spongioform encelphalopathies (TSEs) all manifest
      putatively pathogenic misfolded proteins, suggesting that these proteins or their
      precursors may be targets for therapeutics development efforts. Two different
      biological approaches, both predicated on vaccination, are discussed in this
      monograph as preclinical approaches for the treatment of AD and a TSE. Herein, I
      first describe an active vaccination approach that exploits immune shaping to
      engender a prophylactic T(H)2 response to Abeta in AD mouse models. Second, I
      describe a passive vaccination strategy whereby recombinant adeno-associated
      virus vectored delivery of anti-prion single-chain fragment variable antibodies
      attenuates disease progression and promotes life extension in a mouse TSE model.

PMID- 19399899
TI  - Transplantation of subventricular zone neural precursors induces an endogenous
      precursor cell response in a rat model of Parkinson's disease.
AB  - Realistically, future stem cell therapies for neurological conditions including
      Parkinson's disease (PD) will most probably entail combination treatment
      strategies, involving both the stimulation of endogenous cells and
      transplantation. Therefore, this study investigates these two modes of neural
      precursor cell (NPC) therapy in concert in order to determine their
      interrelationships in a rat PD model. Human placental alkaline phosphatase (hPAP)
      labeled NPCs were transplanted unilaterally into host rats which were
      subsequently infused ipsilaterally with 6-hydroxydopamine (6-OHDA). The reaction
      of host NPCs to the transplantation and 6-OHDA was tracked by bromodeoxyuridine
      (BrdU) labeling. Two weeks after transplantation, in animals transplanted with
      NPCs we found evidence of elevated host subventricular zone NPC proliferation,
      neurogenesis, and migration to the graft site. In these animals, we also observed
      a significant preservation of striatal tyrosine hydroxylase (TH) expression and
      substantia nigra TH cell number. We have seen no evidence that neuroprotection is
      a product of dopamine neuron replacement by NPC-derived cells. Rather, the NPCs
      expressed glial cell line-derived neurotrophic factor (GDNF), sonic hedgehog
      (Shh), and stromal cell-derived factor 1 alpha (SDF1alpha), providing a molecular
      basis for the observed neuroprotection and endogenous NPC response to
      transplantation. In summary, our data suggests plausible synergy between
      exogenous and endogenous NPC actions, and that NPC implantation before the 6-OHDA
      insult can create a host microenvironment conducive to stimulation of endogenous
      NPCs and protection of mature nigral neurons.

PMID- 19399902
TI  - Windows of operation for bioreactor design for the controlled formation of tissue
      engineered arteries.
AB  - The availability of large numbers of units of artificial arteries would offer
      significant benefits to the clinical management of bypass surgery. Tissue
      engineering offers the potential of providing vessels that can mimic the
      morphology, function, and physiological environment of native vessels. Ideally
      this would involve culturing stem cells in vitro within a biodegradable tubular
      scaffold so as to construct tissue for implantation. Essential to establishing a
      robust process for the production of tissue-engineered arteries is the
      understanding of the impact of changes in the operating conditions and bioreactor
      design on the construct formation. In this article, models of transport phenomena
      were developed to predict the critical flow rates and mass transfer requirements
      of a prototype bioreactor for the formation of tissue-engineered arteries. The
      impact of the cell concentration, tube geometry, oxygen effective diffusivity in
      alginate, substrate and metabolite concentration levels, feed rate, and recycle
      rate on the design of the bioreactor was visualized using windows of operation
      and contour plots. The result of this analysis determined the best configuration
      of the bioreactor that meets the cellular transport requirements as well as being
      reliable in performance while seeking to reduce the amount of nutrients to be
      used.

PMID- 19399903
TI  - Effect of periplasmic nitrate reductase on diauxic lag of Paracoccus
      pantotrophus.
AB  - Paracoccus pantotrophus expresses two nitrate reductases-membrane bound nitrate
      reductase (Nar) and periplasmic nitrate reductase (Nap). In growth experiments
      with two denitrifying species (Paracoccus pantotrophus and Alcaligenes eutrophus)
      that have both Nap and Nar and two species (Pseudomonas denitrificans and
      Pseudomonas fluorescens) with Nar only, it was found that diauxic lag is shorter
      for bacteria that express Nap. In P. pantotrophus, napEDABC encodes the
      periplasmic nitrate reductase. To analyze the effect of Nap on diauxic lag, the
      nap operon was deleted from P. pantotrophus. The growth experiments with nap(-)
      mutant resulted in increased diauxic lag when switched from aerobic to anoxic
      respiration, suggesting Nap is responsible for shorter lags and helps in
      adaptation to anoxic metabolism after transition from aerobic conditions.

PMID- 19399904
TI  - Association test of multiallelic gene copy numbers in family trios.
AB  - While recent genomic surveys reveal growing numbers of di-allelic copy number
      variations, it is genes with multiallelic (>2) copy numbers that have shown
      association with distinct phenotypes. Current high-throughput laboratory methods
      are restricted to enumerating total gene copy numbers (GCNs) per individual and
      not the "genotype," i.e. gene copy per chromosome. Thus, association studies of
      multiallelic GCNs have been limited to comparison of median copies in different
      groups. Our new nonparametric statistical approach is based on GCN information
      within a trio-based study design. We present theoretical derivation of the
      statistics and results of simulation studies that show robustness of our approach
      and power under several genetic models.

PMID- 19399905
TI  - On the use of phylogeny-based tests to detect association between quantitative
      traits and haplotypes.
AB  - With the increasing availability of genetic data, several SNPs in a candidate
      gene can be combined into haplotypes to test for association with a quantitative
      trait. When the number of SNPs increases, the number of haplotypes can become
      very large and there is a need to group them together. The use of the
      phylogenetic relationships between haplotypes provides a natural and efficient
      way of grouping. Moreover, it allows us to identify disease or quantitative trait
      related loci. In this article, we describe ALTree-q, a phylogeny-based approach
      to test for association between quantitative traits and haplotypes and to
      identify putative quantitative trait nucleotides (QTN). This study focuses on
      ALTree-q association test which is based on one-way analyses of variance (ANOVA)
      performed at the different levels of the tree. The statistical properties (type
      one error and power rates) were estimated through simulations under different
      genetic models and were compared to another phylogeny-based test, TreeScan,
      (Templeton, 2005) and to a haplotypic omnibus test consisting in a one-way ANOVA
      between all haplotypes. For dominant and additive models ALTree-q is usually the
      most powerful test whereas TreeScan performs better under a recessive model.
      However, power depends strongly on the recurrence rate of the QTN, on the QTN
      allele frequency, and on the linkage disequilibrium between the QTN and other
      markers. An application of the method on Thrombin Activatable Fibronolysis
      Inhibitor Antigen levels in European and African samples confirms a possible
      association with polymorphisms of the CPB2 gene and identifies several QTNs.

PMID- 19399906
TI  - A single-arm, multicenter, open-label phase 2 study of lapatinib as the second
      line treatment of patients with locally advanced or metastatic transitional cell
      carcinoma.
AB  - BACKGROUND: The treatment of recurrent transitional cell carcinoma (TCC) remains
      an unmet clinical need. This study assessed lapatinib, a dual tyrosine kinase
      inhibitor of epidermal growth factor receptor (EGFR) and HER-2, as second-line
      therapy in patients with locally advanced or metastatic TCC. METHODS: This was a
      single-arm, multicenter, open-label, prospective phase 2 study. Patients with TCC
      whose disease progressed on prior platinum-based chemotherapy received lapatinib
      until disease progression or unacceptable toxicity, with evaluations for response
      by Response Evaluation Criteria In Solid Tumors criteria performed every 8 weeks.
      The primary endpoint of the current study was objective tumor response rate.
      Secondary endpoints included safety, time to disease progression, and overall
      survival. RESULTS: Fifty-nine patients were enrolled in the study, 25 of whom
      (42%) could not be evaluated for response. The primary endpoint of an objective
      response rate (ORR) >10% was observed in 1.7% (95% confidence interval [95% CI],
      0.0%-9.1%) of patients; however, 18 (31%; 95% CI, 19%-44%) patients achieved
      stable disease (SD). The median time to disease progression and overall survival
      (OS) were 8.6 weeks (95% CI, 8.0 weeks-11.3 weeks) and 17.9 weeks (95% CI, 13.1
      weeks-30.3 weeks), respectively. Clinical benefit (ORR and SD) was found to be
      correlated with EGFR overexpression (P = .029), and, to some extent, HER-2
      overexpression. The median OS was significantly prolonged in patients with tumors
      that overexpressed EGFR and/or HER-2 (P = .0001). Lapatinib was well tolerated.
      CONCLUSIONS: The study was considered to be negative because it did not meet its
      primary endpoint; however, further analysis demonstrated an improvement in OS in
      a subset of patients with tumors overexpressing EGFR and/or HER-2, which is
      encouraging and warrants further investigation.

PMID- 19399907
TI  - Expression of GFP using Pichia pastoris vectors with zeocin or G-418 sulphate as
      the primary selectable marker.
AB  - Pichia pastoris is a popular host organism for expressing heterologous proteins,
      and various expression vectors for this yeast are currently available. Recently,
      vectors containing novel dominant antibiotic resistance markers have become a
      strong and developing field of research for this methylotropic yeast strain. We
      have developed new P. pastoris expression vectors, the pPICKanMX6 and
      pPICKanMX6alpha series. These vectors were constructed by replacing the zeocin
      resistance gene of the pPICZA, B, C and pPICZalphaA, B and C vectors with the
      Tn903 kan(R) marker from pFA6a KanMX6, which confers G-418 sulphate resistance in
      P. pastoris. The limits of antibiotic resistance in two transformant yeast
      strains were investigated, and the selection marker was shown to be stably
      retained. To demonstrate their usefulness, a gene encoding hexa-histidine-tagged
      green fluorescent protein (GFPH6) was cloned into one of the new vectors and GFP
      expression examined in P. pastoris cells. The protein expression levels using the
      pPICKanMX6B vector were comparable with that using the original plasmid, based on
      zeocin resistance as seen by yeast cell fluorescence. Moreover, GFPH6 was able to
      be isolated by immobilized metal ion affinity chromatography (IMAC) from lysates
      of both yeast strains. A model reporter construct has been used to demonstrate
      successful recombinant protein expression and its subsequent purification using
      these new vectors. Corresponding vectors can now also be engineered with foreign
      gene expression under the control of various different promoters, to increase the
      flexibility of P. pastoris as a cellular factory for heterologous protein
      production.

PMID- 19399908
TI  - Hepatic progenitor cell-mediated regeneration and fibrosis: chicken or egg?

PMID- 19399909
TI  - The Hsp90/Cdc37p chaperone system is a determinant of molybdate resistance in
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae lacks enzymes that contain the molybdopterin co-factor
      and therefore any requirement for molybdenum as a trace mineral supplement.
      Instead, high molybdate levels are inhibitory to its growth. Low cellular levels
      of heat shock protein 90 (Hsp90), an essential chaperone, were found to enhance
      this sensitivity to molybdate. Certain Hsp90 point mutations and co-chaperone
      protein defects that partially compromise the function of the Hsp90/Cdc37p
      chaperone system also rendered S. cerevisiae hypersensitive to high molybdate
      levels. Sensitivity was especially apparent with mutations close to the Hsp90
      nucleotide binding site, with the loss of the non-essential co-chaperone Sti1p
      (the equivalent of mammalian Hop), and with the abolition of residue Ser14
      phosphorylation on the essential co-chaperone Cdc37p. While it remains to be
      proved that these effects reflect direct inhibition of the Hsp90 of the cell by
      the MoO(4) (2+) oxyanion in vivo; this possibility is suggested by molybdate
      sensitivity arising with a mutation in the Hsp90 nucleotide binding site that
      does not generate stress sensitivity or an impaired stress response. Molybdate
      sensitivity may therefore be a useful phenotype to score when studying mutations
      in this chaperone system.

PMID- 19399910
TI  - Hepatology as a model for health care.

PMID- 19399912
TI  - Vascular disorders of the liver.

PMID- 19399911
TI  - Association between hypothyroidism and hepatocellular carcinoma: a case-control
      study in the United States.
AB  - Thyroid hormones play an essential role in lipid mobilization, lipid degradation,
      and fatty acid oxidation. Hypothyroidism has been associated with nonalcoholic
      steatohepatitis; however, the association between thyroid diseases and
      hepatocellular carcinoma (HCC) in men and women has not been well established. We
      investigated the association between hypothyroidism and HCC risk in men and women
      in a case-control study, which included 420 eligible patients with HCC and 1104
      healthy controls. We used multivariate unconditional logistic regression models
      to control for the confounding effects of established HCC risk factors. A long
      term history of hypothyroidism (>10 years) was associated with a statistically
      significant high risk of HCC in women; after adjusting for demographic factors,
      diabetes, hepatitis, alcohol consumption, cigarette smoking, and family history
      of cancer, the odds ratio (OR) was 2.9 (95% confidence interval [CI], 1.3-6.3).
      Restricted analyses among hepatitis virus-negative subjects, nondrinkers,
      nondiabetics, nonsmokers, and nonobese individuals indicated a significant
      association between hypothyroidism and HCC, with an approximate two-fold to three
      fold increased risk of HCC development. We observed risk modification among women
      with diabetes mellitus (OR = 9.4; 95% CI = 2.7-32.7) and chronic hepatitis virus
      infection (OR = 31.2; 95% CI = 6.3-153.2). A history of hyperthyroidism was not
      significantly related to HCC (OR = 1.7; CI = 0.6-5.1). We noted significant
      elevated risk association between hypothyroidism and HCC in women that was
      independent of established HCC risk factors. Experimental investigations are
      necessary for thorough assessment of the relationship between thyroid disorders
      and HCC.

PMID- 19399913
TI  - Quantitation of NAD+ biosynthesis from the salvage pathway in Saccharomyces
      cerevisiae.
AB  - Nicotinamide adenine dinucleotide (NAD+) is synthesized via two major pathways in
      prokaryotic and eukaryotic systems: the de novo biosynthesis pathway from
      tryptophan precursors, or the salvage biosynthesis pathway from either
      extracellular nicotinic acid or various intracellular NAD+ decomposition
      products. NAD+ biosynthesis via the salvage pathway has been linked to an
      increase in yeast replicative lifespan under calorie restriction (CR). However,
      the relative contribution of each pathway to NAD+ biosynthesis under both normal
      and CR conditions is not known. Here, we have performed lifespan, NAD+ and NADH
      (the reduced form of NAD+) analyses on BY4742 wild-type, NAD+ salvage pathway
      knockout (npt1Delta) and NAD+ de novo pathway knockout (qpt1Delta) yeast strains
      cultured in media containing either 2% glucose (normal growth) or 0.5% glucose
      (CR). We have utilized 14C labelled nicotinic acid in the culture media combined
      with HPLC speciation and both UV and 14C detection to quantitate the total
      amounts of NAD+ and NADH and the amounts derived from the salvage pathway. We
      observed that wild-type and qpt1Delta yeast exclusively utilized extracellular
      nicotinic acid for NAD+ and NADH biosynthesis under both the 2% and 0.5% glucose
      growth conditions, suggesting that the de novo pathway plays little role if a
      functional salvage pathway is present. We also observed that NAD+ concentrations
      decreased in all three strains under CR. However, unlike the wild-type strain,
      NADH concentrations did not decrease and NAD+: NADH ratios did not increase under
      CR for either knockout strain. Lifespan analyses revealed that CR resulted in a
      lifespan increase of approximately 25% for the wild-type and qpt1Delta strains,
      while no increase in lifespan was observed for the npt1Delta strain. In
      combination, these data suggest that having a functional salvage pathway is
      required for lifespan extension under CR.

PMID- 19399914
TI  - Dysregulation of glutathione synthesis during cholestasis in mice: molecular
      mechanisms and therapeutic implications.
AB  - Glutathione (GSH) provides important antioxidant defense and regulates multiple
      critical processes including fibrogenesis. There are conflicting literature
      studies regarding changes in GSH during cholestasis. Here we examined changes in
      the GSH synthetic enzymes during bile duct ligation (BDL) in mice and how
      treatment with ursodeoxycholic acid (UDCA) and/or S-adenosylmethionine (SAMe)
      affects the expression of these enzymes and liver injury. The hepatic expression
      of glutamate-cysteine ligase (GCL) subunits and GSH synthase (GS) increased
      transiently after BDL but fell to 50% of baseline by 2 weeks. Nuclear factor
      erythroid 2-related factor 2 (Nrf2) trans-activates gene expression by way of the
      antioxidant response element (ARE), which controls the expression of all three
      genes. Despite increased Nrf2 nuclear levels, Nrf2 nuclear binding to ARE fell 2
      weeks after BDL. Nuclear levels of c-Maf and MafG, which can negatively regulate
      ARE, were persistently induced during BDL and the dominant proteins bound to ARE
      on day 14. UDCA and SAMe induced the expression of GCL subunits and raised GSH
      levels. They increased nuclear Nrf2 levels, prevented c-Maf and MafG induction,
      and prevented the fall in Nrf2 nuclear binding to ARE. Combined treatment had
      additive effects, reduced liver cell death, and prevented fibrosis. CONCLUSION:
      GSH synthesis falls during later stages of BDL due to lower expression of GSH
      synthetic enzymes. UDCA and SAMe treatment prevented this fall and combined
      therapy was more effective on preserving GSH levels and preventing liver injury.

PMID- 19399915
TI  - Comparative analysis of the performance of commonly available density functionals
      in the determination of geometrical parameters for zinc complexes.
AB  - A set of 44 Zinc-ligand bond-lengths and of 60 ligand-metal-ligand bond angles
      from 10 diverse transition-metal complexes, representative of the coordination
      spheres of typical biological Zn systems, were used to evaluate the performance
      of a total of 18 commonly available density functionals in geometry
      determination. Five different basis sets were considered for each density
      functional, namely two all-electron basis sets (a double-zeta and triple-zeta
      formulation) and three basis sets including popular types of effective-core
      potentials: Los Alamos, Steven-Basch-Krauss, and Stuttgart-Dresden. The results
      show that there are presently several better alternatives to the popular B3LYP
      density functional for the determination of Zn-ligand bond-lengths and angles.
      BB1K, MPWB1K, MPW1K, B97-2 and TPSS are suggested as the strongest alternatives
      for this effect presently available in most computational chemistry software
      packages. In addition, the results show that the use of effective-core potentials
      (in particular Stuttgart-Dresden) has a very limited impact, in terms of
      accuracy, in the determination of metal-ligand bond-lengths and angles in Zinc
      complexes, and is a good and safe alternative to the use of an all-electron basis
      set such as 6-31G(d) or 6-311G(d,p).

PMID- 19399916
TI  - An exploration of reminiscence and post-war European immigrants living in a
      multicultural aged-care setting in Australia.
AB  - This phenomenological study explores the experiences and perceptions of the
      telling of life stories of four post-war immigrants living in a multicultural
      residential aged-care setting in Australia. This study aims to shed light on what
      participants feel about life stories, and the prospect of involvement in the
      documentation of their life story in order to provide insight and understanding
      for optimum programme facilitation and better resident care.Semi-structured
      interviews were conducted with the four participants. Data were audiotaped and
      transcribed. Phenomenological methods were used to explicate data.Three main
      themes emerged: diminution of guilt, social sharing - common bonds and, the urge
      to 'feel' the past to 'fill' the present. It is apparent that aged survivors of
      war, and displacement to a new country, feel residual guilt regarding the leaving
      of their homeland. The prospect of documenting their life stories offers an
      opportunity to provide an explanation for their decision.Immersion in life
      stories allows the re-experiencing and sharing of past emotions and sensations.
      Engagement in occupational reminiscence enhances understanding a person's lived
      life experience, which adds meaning to one's life.

PMID- 19399917
TI  - Respiratory symptoms in young infancy: child, parent and physician related
      determinants of drug prescription in primary care.
AB  - PURPOSE: Respiratory symptoms account for the majority of drug prescriptions in
      the first year of life. We investigated the influence of child, parent and
      physician factors on drug prescriptions for respiratory symptoms in primary care
      in infancy. METHODS: Infants participated in the WHeezing Illnesses STudy
      LEidsche Rijn (WHISTLER), a prospective birth cohort on respiratory illnesses.
      Outcome was defined as having received a prescription of antibiotics or of anti
      asthma medication for respiratory symptoms by a physician. RESULTS: Nearly 60% of
      all children ever visited a physician for respiratory symptoms during the first
      year of life, of which 40% received a prescription. Every extra day with symptoms
      during the month before consultation and each extra visit to a physician were
      associated with a higher chance for prescription (respectively odds ratios (OR)
      1.07/2.63, 95% confidence intervals (CI) 1.02-1.12/1.83-3.76). Further, we found
      a higher chance for drug prescribing for boys (2.7, 2.0-3.7), children attending
      day care (1.17, 1.09-1.25), mothers with higher education (2.3, 1.2-4.6), working
      mothers (4.5, 0.9-22.0) and older mothers (years) (1.09, 1.02-1.16). Furthermore,
      physicians' years of experience was a determinant for receiving a prescription
      (2.5, 1.1-6.0). Accounting for symptoms and visits as strong predictors of
      prescribing, infant gender and day care attendance were still predictors.
      Furthermore, infant gender, day care attendance, family history of asthma and
      physicians' years of experience were independent determinants of the number of
      prescriptions besides symptoms and visits. CONCLUSION: In young infancy, besides
      the severity of symptoms there are child, physician and particularly maternal
      characteristics that influence the decision of general practitioners to prescribe
      drugs for respiratory symptoms.

PMID- 19399918
TI  - Clinical and demographic characteristics of patients receiving different oral
      hypoglycemic agents.
AB  - OBJECTIVE: To characterize the demographic and clinical profiles of older persons
      with diabetes treated with a thiazolidinedione (TZD) in comparison to other
      groups of patients, including all patients with diabetes and those taking other
      oral hypoglycemic agents (OHAs). RESEARCH DESIGN AND METHODS: We studied Ontario
      residents aged 66 and older and alive on 31 March 2008. Five groups were created
      based on diabetes status and history of treatment with OHAs, including patients
      prescribed rosiglitazone, patients prescribed pioglitazone, and a sample of three
      other groups: patients prescribed any other OHA in the preceding year, all
      patients with diabetes, and elderly Ontarians regardless of diabetes status. We
      excluded patients receiving insulin or multiple TZDs from the three OHA groups.
      Study groups were compared based on demographic information, measures of
      comorbidity, history of cardiovascular diseases, and concomitant use of drugs for
      cardiovascular disease. RESULTS: People treated with pioglitazone (n = 16 206)
      were highly similar to those treated with rosiglitazone (n = 16 066). Individuals
      treated with either TZD tended to be younger, less likely to reside in a long
      term care facility, and had similar cardiovascular profiles to samples of
      patients with diabetes (n = 50 000) and those taking other OHAs (n = 50 000).
      CONCLUSIONS: Older patients started on TZDs have cardiovascular risk profiles
      comparable to other individuals with diabetes, including those taking other OHAs,
      suggesting that observational studies of TZD safety are not likely confounded by
      selection bias.

PMID- 19399919
TI  - Estimating ethnic differences in self-reported new use of antidepressant
      medications: results from the Multi-Ethnic Study of Atherosclerosis.
AB  - INTRODUCTION: There is evidence that the utilization of antidepressant
      medications (ADM) may vary between different ethnic groups in the United States
      population. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a
      population-based prospective cohort study of 6814 US adults from 4 different
      ethnic groups. After excluding baseline users of ADM, we examined the relation
      between baseline depression and new use of ADM for 4 different ethnicities:
      African-Americans (n = 1822), Asians (n = 784) Caucasians (n = 2300), and
      Hispanics (n = 1405). Estimates of the association of ethnicity and ADM use were
      adjusted for age, study site, gender, Center for Epidemiologic Studies Depression
      Scale (CES-D), alcohol use, smoking, blood pressure, diabetes, education, and
      exercise. Non-random loss to follow-up was present and estimates were adjusted
      using inverse probability of censoring weighting (IPCW). RESULTS: Of the four
      ethnicities, Caucasian participants had the highest rate of ADM use (12%)
      compared with African-American (4%), Asian (2%), and Hispanic (6%) participants.
      After adjustment, non-Caucasian ethnicity was associated with reduced ADM use:
      African-American (HR: 0.42; 95% Confidence Interval (CI): 0.31-0.58), Asian (HR:
      0.14; 95%CI: 0.08-0.26), and Hispanic (HR: 0.47; 95%CI: 0.31-0.65). Applying IPCW
      to correct for non-random loss to follow-up among the study participants weakened
      but did not eliminate these associations: African-American (HR: 0.48; 95%CI: 0.30
      0.57), Asian (HR: 0.23; 95%CI: 0.13-0.37), and Hispanic (HR: 0.58; 95%CI: 0.47
      0.67). CONCLUSION: Non-Caucasian ethnicity is associated with lower rates of new
      ADM use. After IPCW adjustment, the observed ethnicity differences in ADM use are
      smaller although still statistically significant.

PMID- 19399920
TI  - Involvement of the nucleolus in replication of human viruses.
AB  - Viruses are intracellular pathogens that have to usurp some of the cellular
      machineries to provide an optimal environment for their own replication. An
      increasing number of reports reveal that many viruses induce modifications of
      nuclear substructures including nucleoli, whether they replicate or not in the
      nucleus of infected cells. Indeed, during infection of cells with various types
      of human viruses, nucleoli undergo important morphological modifications. A large
      number of viral components traffic to and from the nucleolus where they interact
      with different cellular and/or viral factors, numerous host nucleolar proteins
      are redistributed in other cell compartments or are modified and some cellular
      proteins are delocalized in the nucleolus of infected cells. Well-documented
      studies have established that several of these nucleolar modifications play a
      role in some steps of the viral cycle, and also in fundamental cellular pathways.
      The nucleolus itself is the place where several essential steps of the viral
      cycle take place. In other cases, viruses divert host nucleolar proteins from
      their known functions in order to exert new unexpected role(s).

PMID- 19399921
TI  - Involvement of histidines 11, 15 and 19 in the binding of zinc to the fusogenic
      H5WYG peptide.
AB  - The histidine-rich GLFHAIAHFIHGGWHGLIHGWYG peptide (H5WYG) coordinates a Zn2+ ion
      and forms a stable peptide-metal complex promoting membrane fusion at physiologic
      pH. In our previous article titled 'Histidine-rich peptide: evidence for a single
      zinc-binding site on H5WYG peptide that promotes membrane fusion at neutral pH'
      in Journal of Mass Spectrometry (2009, 44, 81-89), tandem mass spectrometry
      experiments have provided evidence for the binding of a single Zn2+ ion to H5WYG
      and suggested that this binding is shared between H11, H19 and probably H15
      residues. To clarify the involvement of these histidine residues in the binding
      to the Zn2+ ion and especially to remove the doubt about the implication of the
      H15 residue, here we have used three H5WYG mutants termed H5WYGH11A, H5WYGH15A
      and H5WYGH19A, whose H11, H15 and H19 residues were replaced with an alanine
      residue. The novelty introduced by these new tandem mass spectrometry experiments
      performed with the mutants is the demonstration that H15 is involved in the
      binding of the single Zn2+ ion and that it may even favour the setting of another
      Zn2+ ion. Thus, the three histidines H11, H15 and H19 could lead to a specific
      structuring of H5WYG that can promote membrane fusion upon the binding of zinc.

PMID- 19399922
TI  - Surgical treatment of anal stenosis.
AB  - Anal stenosis is a rare but serious complication of anorectal surgery, most
      commonly seen after hemorrhoidectomy. Anal stenosis represents a technical
      challenge in terms of surgical management. A Medline search of studies relevant
      to the management of anal stenosis was undertaken. The etiology, pathophysiology
      and classification of anal stenosis were reviewed. An overview of surgical and
      non-surgical therapeutic options was developed. Ninety percent of anal stenosis
      is caused by overzealous hemorrhoidectomy. Treatment, both medical and surgical,
      should be modulated based on stenosis severity. Mild stenosis can be managed
      conservatively with stool softeners or fiber supplements. Sphincterotomy may be
      quite adequate for a patient with a mild degree of narrowing. For more severe
      stenosis, a formal anoplasty should be performed to treat the loss of anal canal
      tissue. Anal stenosis may be anatomic or functional. Anal stricture is most often
      a preventable complication. Many techniques have been used for the treatment of
      anal stenosis with variable healing rates. It is extremely difficult to interpret
      the results of the various anaplastic procedures described in the literature as
      prospective trials have not been performed. However, almost any approach will at
      least improve patient symptoms.

PMID- 19399923
TI  - Measurement of serum paraoxonase-1 activity in the evaluation of liver function.
AB  - Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and
      found in the circulation associated with high-density lipoproteins. The
      physiological function of PON1 seems to be to degrade specific oxidized
      cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes.
      PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels
      have been reported in a variety of diseases involving oxidative stress including
      chronic liver diseases. Measurement of serum PON1 activity has been proposed as a
      potential test for the evaluation of liver function. However, this measurement is
      still restricted to research and has not been extensively applied in routine
      clinical chemistry laboratories. The reason for this restriction is due to the
      problem that the substrate commonly used for PON1 measurement, paraoxon, is toxic
      and unstable. The recent development of new assays with non-toxic substrates
      makes this proposal closer to a practical development. The present editorial
      summarizes PON1 biochemistry and function, its involvement with chronic liver
      impairment, and some aspects related to the measurement of PON1 activity in
      circulation.

PMID- 19399924
TI  - Five years' experience with capsule endoscopy in a single center.
AB  - Capsule endoscopy (CE) is a novel technology that facilitates highly effective
      and noninvasive imaging of the small bowel. Although its efficacy in the
      evaluation of obscure gastrointestinal bleeding (OGIB) has been proven in several
      trials, data on uses of CE in different small bowel diseases are rapidly
      accumulating in the literature, and it has been found to be superior to
      alternative diagnostic tools in a range of such diseases. Based on literature
      evidence, CE is recommended as a first-line investigation for OGIB after negative
      bidirectional endoscopy. CE has gained an important role in the diagnosis and
      follow-up of Crohn's disease and celiac disease and in the surveillance of small
      bowel tumors and polyps in selected patients. Capsule retention is the major
      complication, with a frequency of 1%-2%. The purpose of this review was to
      discuss the procedure, indications, contraindications and adverse effects
      associated with CE. We also review and share our five-year experience with CE in
      various small bowel diseases. The recently developed balloon-assisted
      enteroscopies have both diagnostic and therapeutic capability. At the present
      time, CE and balloon-assisted enteroscopies are complementary techniques in the
      diagnosis and management of small bowel diseases.

PMID- 19399926
TI  - Histological and biochemical alterations in early-stage lobar ischemia
      reperfusion in rat liver.
AB  - AIM: To investigate the structural and biochemical changes in the early stage of
      reperfusion in the rat livers exposed to lobar ischemia-reperfusion (IR).
      METHODS: The median and left lobes of the liver were subjected to 60 min ischemia
      followed by 5, 10, 30, 45, 60 and 120 min reperfusion. Blood samples were taken
      at different time intervals to test enzyme activities and biochemical alterations
      induced by reperfusion. At the end of each reperfusion period, the animals were
      killed by euthanasia and tissue samples were taken for histological examination
      and immunohistochemistry. RESULTS: Cell vacuolation, bleb formation and focal
      hepatitis were the most important changes occur during ischemia. While some
      changes including bleb formation were removed during reperfusion, other
      alterations including portal hepatitis, inflammation and the induction of
      apoptosis were seen during this stage. The occurrence of apoptosis, as
      demonstrated by apoptotic cells and bodies, was the most important histological
      change during reperfusion. The severity of apoptosis was dependent on the time of
      reperfusion, and by increasing the time of reperfusion, the numbers of apoptotic
      bodies was significantly enhanced. The amounts of lactate dehydrogenase, alanine
      aminotransferase, aspartate aminotransferase, creatinine and urea were
      significantly increased in serum obtained from animals exposed to hepatic IR.
      CONCLUSION: Inflammation and subsequent apoptotic cell death were the most
      important changes in early-stage hepatic reperfusion injury, and the number of
      apoptotic bodies increased with time of reperfusion.

PMID- 19399925
TI  - Effects and mechanisms of silibinin on human hepatocellular carcinoma xenografts
      in nude mice.
AB  - AIM: To investigate the in vivo effects and mechanisms of silibinin on the growth
      of hepatocellular carcinoma (HCC) xenografts in nude mice. METHODS: Nude mice
      bearing HuH7 xenografts were used to assess the anti-HCC effects and mechanisms
      of silibinin. RESULTS: Silibinin resulted in a potent dose-dependent reduction of
      HuH7 xenografts in association with a significant decrease in Ki-67 and alpha
      fetoprotein production, nuclear NF-kappaB content, polo-like kinase 1, Rb
      phosphorylation, and E2F1/DP1 complex, but increased p27/CDK4 complex and
      checkpoint kinase 1 expression, suggesting that the in vivo effects of silibinin
      are mediated by inhibiting G1-S transition of the cell cycle. Silibinin-induced
      apoptosis of HuH7 xenografts was associated with inhibited survivin
      phosphorylation. Silibinin-reduced growth of HuH7 xenografts was associated with
      decreased p-ERK, increased PTEN expression and the activity of silibinin was
      correlated with decreased p-Akt production, indicating involvement of
      PTEN/PI(3)K/Akt and ERK pathways in its in vivo anti-HCC effects. Silibinin
      reduced growth of HuH7 xenografts was also associated with a significant increase
      in AC-H3 and AC-H4 expression and the production of superoxide dismutase (SOD)-1.
      CONCLUSION: Silibinin reduces HCC xenograft growth through the inhibition of cell
      proliferation, cell cycle progression and PTEN/P-Akt and ERK signaling, inducing
      cell apoptosis, and increasing histone acetylation and SOD-1 expression.

PMID- 19399927
TI  - Rocket "Eruca sativa": a salad herb with potential gastric anti-ulcer activity.
AB  - AIM: To validate gastric anti-ulcer properties of Rocket "Eruca sativa" on
      experimentally-induced gastric secretion and ulceration in albino rats. METHODS:
      Gastric acid secretion studies were undertaken using pylorus-ligated rats.
      Gastric lesions in the rats were induced by noxious chemicals including ethanol,
      strong alkalis, indomethacin and hypothermic restraint stress. The levels of
      gastric wall mucus (GWM), nonprotein sulfhydryls (NP-SH) and malondialdehyde
      (MDA) were also measured in the glandular stomach of rats following ethanol
      administration. The gastric tissue was also examined histologically. The extract
      was used in two doses (250 and 500 mg/kg body weight) in all experiments.
      RESULTS: In pylorus-ligated Shay rats, the ethanolic extract of Rocket "Eruca
      sativa L." (EER) significantly and dose-dependently reduced the basal gastric
      acid secretion, titratable acidity and ruminal ulceration. Rocket extract
      significantly attenuated gastric ulceration induced by necrotizing agents (80%
      ethanol, 0.2 mol/L NaOH, 25% NaCl), indomethacin and hypothermic restraint
      stress. The anti-ulcer effect was further confirmed histologically. On the other
      hand, the extract significantly replenished GWM and NP-SH levels, as well as the
      MDA level significantly reduced by extract pretreatment. CONCLUSION: Rocket
      extract possesses anti-secretory, cytoprotective, and anti-ulcer activities
      against experimentally-induced gastric lesions. The anti-ulcer effect is possibly
      through prostaglandin-mediated activity and/or through its anti-secretory and
      antioxidant properties.

PMID- 19399928
TI  - In vitro and in vivo suppression of hepatocellular carcinoma growth by midkine
      antisense oligonucleotide-loaded nanoparticles.
AB  - AIM: To synthesize antisense oligonucleotides (ASODNs) of midkine (MK), package
      the ASODNs with nanoparticles, and to inhibit hepatocellular carcinoma (HCC)
      growth using these nanoparticles. METHODS: HepG2 cell proliferation was analyzed
      in vitro using the 3-(4,5-dimethythiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2Htetrazolium, inner salt assay. The in vivo activity of
      nanoparticles delivering the MK-ASODNs was analyzed by histopathological and
      immunohistochemical staining and quantitative real time polymerase chain reaction
      (PCR). RESULTS: The in vitro proliferation of HepG2 cells was significantly
      inhibited by the nanoparticles packaged with MK-ASODNs (NANO-ASODNs).
      Furthermore, the NANO-ASODNs significantly inhibited the growth of HCC in the
      mouse model. CONCLUSION: NANO-ASODNs can significantly suppress the growth of HCC
      in vitro and in vivo.

PMID- 19399929
TI  - Colonoscopic polypectomy in anticoagulated patients.
AB  - AIM: To review our experience performing polypectomy in anticoagulated patients
      without interruption of anticoagulation. METHODS: Retrospective chart review at
      the Veterans Affairs Palo Alto Health Care System. Two hundred and twenty five
      polypectomies were performed in 123 patients. Patients followed a standardized
      protocol that included stopping warfarin for 36 h to avoid supratherapeutic
      anticoagulation from the bowel preparation. Patients with lesions larger than 1
      cm were generally rescheduled for polypectomy off warfarin. Endoscopic clips were
      routinely applied prophylactically. RESULTS: One patient (0.8%, 95% CI: 0.1%
      4.5%) developed major post-polypectomy bleeding that required transfusion. Two
      others (1.6%, 95% CI: 0.5%-5.7%) had self-limited hematochezia at home and did
      not seek medical attention. The average polyp size was 5.1 +/- 2.2 mm.
      CONCLUSION: Polypectomy can be performed in therapeutically anticoagulated
      patients with lesions up to 1 cm in size with an acceptable bleeding rate.

PMID- 19399930
TI  - Effect of dephytinization on bioavailability of iron, calcium and zinc from
      infant cereals assessed in the Caco-2 cell model.
AB  - AIM: To test the effect of the dephytinization of three different commercial
      infant cereals on iron, calcium, and zinc bioavailability by estimating the
      uptake, retention, and transport by Caco-2 cells. METHODS: Both dephytinized (by
      adding an exogenous phytase) and non-dephytinized infant cereals were digested
      using an in vitro digestion protocol adapted to the gastrointestinal conditions
      of infants younger than 6 mo. Mineral cell retention, transport, and uptake from
      infant cereals were measured using the soluble fraction of the simulated
      digestion and the Caco-2 cells. RESULTS: Dephytinization of infant cereals
      significantly increased (P < 0.05) the cell uptake efficiency (from 0.66%-6.05%
      to 3.93%-13%), retention (from 6.04%-16.68% to 14.75%-20.14%) and transport
      efficiency (from 0.14%-2.21% to 1.47%-6.02%), of iron, and the uptake efficiency
      (from 5.0%-35.4% to 7.3%-41.6%) and retention (from 4.05%-20.53% to 14.45%-61.3%)
      of zinc, whereas calcium only cell uptake showed a significant increase (P <
      0.05) after removing phytate from most of the samples analyzed. A positive
      relationship (P < 0.05) between mineral solubility and the cell uptake and
      transport efficiencies was observed. CONCLUSION: Removing phytate from infant
      cereals had a beneficial effect on iron and zinc bioavailability when infant
      cereals were reconstituted with water. Since in developing countries cereal-based
      complementary foods for infants are usually consumed mixed with water, exogenous
      phytase additions could improve the nutritional value of this weaning food.

PMID- 19399931
TI  - Intussusception in adults: clinical characteristics, diagnosis and operative
      strategies.
AB  - AIM: To evaluate 20 adults with intussusception and to clarify the cause,
      clinical features, diagnosis, and management of this uncommon entity. METHODS: A
      retrospective review of patients aged > 18 years with a diagnosis of intestinal
      intussusception between 2000 and 2008. Patients with rectal prolapse, prolapse of
      or around an ostomy and gastroenterostomy intussusception were excluded. RESULTS:
      There were 20 cases of adult intussusception. Mean age was 47.7 years. Abdominal
      pain, nausea, and vomiting were the most common symptoms. The majority of
      intussusceptions were in the small intestine (85%). There were three (15%) cases
      of colonic intussusception. Enteric intussusception consisted of five
      jejunojejunal cases, nine ileoileal, and four cases of ileocecal invagination.
      Among enteric intussusceptions, 14 were secondary to a benign process, and in one
      of these, the malignant cause was secondary to metastatic lung adenocarcinoma.
      All colonic lesions were malignant. All cases were treated surgically.
      CONCLUSION: Adult intussusception is an unusual and challenging condition and is
      a preoperative diagnostic problem. Treatment usually requires resection of the
      involved bowel segment. Reduction can be attempted in small-bowel intussusception
      if the segment involved is viable or malignancy is not suspected; however, a more
      careful approach is recommended in colonic intussusception because of a
      significantly higher coexistence of malignancy.

PMID- 19399932
TI  - Computer simulation of flow and mixing at the duodenal stump after gastric
      resection.
AB  - AIM: To investigate the flow and mixing at the duodenal stump after gastric
      resection, a computer simulation was implemented. METHODS: Using the finite
      element method, two different Billroth II procedure cases (A and B) were modeled.
      Case A was defined with a shorter and almost straight duodenal section, while
      case B has a much longer and curved duodenal section. Velocity, pressure and food
      concentration distribution were determined and the numerical results were
      compared with experimental observations. RESULTS: The pressure distribution
      obtained by numerical simulation was in the range of the recorded experimental
      results. Case A had a more favorable pressure distribution in comparison with
      case B. However, case B had better performance in terms of food transport because
      of more continual food distribution, as well as better emptying of the duodenal
      section. CONCLUSION: This study offers insight into the transport process within
      the duodenal stump section after surgical intervention, which can be useful for
      future patient-specific predictions of a surgical outcome.

PMID- 19399933
TI  - Transjugular intrahepatic portosystemic shunt in liver transplant recipients.
AB  - AIM: To evaluate the efficacy of transjugular intrahepatic portosystemic shunts
      (TIPSs) after liver transplantation (LT). METHODS: Between November 1996 and
      December 2005, 10 patients with severe recurrent hepatitis C virus infection (n =
      4), ductopenic rejection (n = 5) or portal vein thrombosis (n = 1) were included
      in this analysis. Eleven TIPSs (one patient underwent two TIPS procedures) were
      placed for management of therapy-refractory ascites (n = 7), hydrothorax (n = 2)
      or bleeding from colonic varices (n = 1). The median time interval between LT and
      TIPS placement was 15 (4-158) mo. RESULTS: TIPS placement was successful in all
      patients. The mean portosystemic pressure gradient was reduced from 12.5 to 8.7
      mmHg. Complete and partial remission could be achieved in 43% and 29% of patients
      with ascites. Both patients with hydrothorax did not respond to TIPS. No
      recurrent bleeding was seen in the patient with colonic varices. Nine of 10
      patients died during the study period. Only one of two patients, who underwent
      retransplantation after the TIPS procedure, survived. The median survival period
      after TIPS placement was 3.3 (range 0.4-20) mo. The majority of patients died
      from sepsis with multiorgan failure. CONCLUSION: Indications for TIPS and
      technical performance in LT patients correspond to those in non-transplanted
      patients. At least partial control of therapy-refractory ascites and variceal
      bleeding could be achieved in most patients. Nevertheless, survival rates were
      disappointing, most probably because of the advanced stages of liver disease at
      the time of TIPS placement and the high risk of sepsis as a consequence of
      immunosuppression.

PMID- 19399934
TI  - Efficacy of perioperative parecoxib injection on postoperative pain relief after
      laparoscopic cholecystectomy: a prospective, randomized study.
AB  - AIM: To determine the efficacy of perioperative parecoxib injection on
      postoperative pain relief after laparoscopic cholecystectomy. METHODS: A
      prospective, double-blind, randomized, placebo-controlled study was conducted on
      70 patients who underwent elective laparoscopic cholecystectomy under general
      anesthesia at Siriraj Hospital, Bangkok, from January 2006 to December 2007.
      Patients were randomized to receive either 20 mg parecoxib infusion 30 min before
      induction of anesthesia and at 12 h after the first dose (treatment group), or
      normal saline infusion, in the same schedule, as a placebo (control group). The
      degree of the postoperative pain was assessed every 3 h in the first 24 h after
      surgery, and then every 12 h the following day, using a visual analog scale. The
      consumption of analgesics was also recorded. RESULTS: There were 40 patients in
      the treatment group, and 30 patients in the control group. The pain scores at
      each time point, and analgesic consumption did not differ between the two groups.
      However, there were fewer patients in the treatment group than placebo group who
      required opioid infusion within the first 24 h (60% vs 37%, P = 0.053).
      CONCLUSION: Perioperative administration of parecoxib provided no significant
      effect on postoperative pain relief after laparoscopic cholecystectomy. However,
      preoperative infusion 20 mg parecoxib could significantly reduce the
      postoperative opioid consumption.

PMID- 19399935
TI  - Effect of Lianshu preparation on lipopolysaccharide-induced diarrhea in rats.
AB  - AIM: To investigate the effect of Lianshu preparation on lipopolysaccharide (LPS)
      induced diarrhea in rats. METHODS: A diarrhea model was established in Sprague
      Dawley rats via injection of 1 mL of 30 mg/kg LPS. A total of 40 rats were
      randomly divided into normal group, LPS group, LPS + Lianshu group, LPS +
      berberine group (n = 10 in each group). Their intestinal mucosal barrier and
      frequency of diarrhea were observed. Levels of glucose, serum Na(+), K(+), Cl(-)
      and hematocrit, plasma nitrogen monoxide (NO), diamine oxidase (DAO), and D (-)
      lactate were measured. The number of IgA+ plasma cells in small intestine was
      detected and SIgA levels in the intestinal fluid were measured. The antipyretic
      activity of Lianshu preparation in rats was evaluated using Brewer's yeast
      induced pyrexia (10 mL/kg of 20% aqueous suspension). Acetaminophen (250 mg/kg,
      intragastric administration, bid) was used as a standard drug for comparison.
      Temperature was recorded 1 h before and 6 h after Brewer's yeast injection.
      Finally, small intestinal transmission in mice treated with Lianshu was detected
      after intraperitoneal injection of methyl prostigmin (2 mg/kg). Atropine (10
      g/kg) was used as a control. The ink content in intestine was determined and the
      total length of intestine was measured. RESULTS: The frequency of diarrhea was
      higher in LPS group than in LPS + Lianshu group and LPS + berberine group (36.70
      +/- 5.23 vs 28.50 +/- 4.06 and 32.70 +/- 9.30 respectively, P < 0.01), and lower
      in LPS + Lianshu group than in LPS + berberine group (P = 0.03). The levels of
      Na(+), glucose, Cl(-), K(+) were significantly lower in LPS + Lianshu group than
      in LPS + berberine group (140.35 +/- 3.19 mmol/L vs 131.99 +/- 4.86 mmol/L, 8.49
      +/- 1.84 mmol/L vs 6.54 +/- 2.30 mmol/L, 106.29 +/- 4.41 mmol/L vs 102.5 +/- 1.39
      mmol/L, 5.08 +/- 0.66 mmol/L vs 4.32 +/- 0.62 mmol/L respectively, P < 0.05). The
      level of hematocrit was lower in LPS + Lianshu group than in LPS + berberine
      group (0.50% +/- 0.07% vs 0.59% +/- 0.10% respectively, P < 0.05). The plasma
      levels of NO, DAO and D (-)-lactate were higher in LPS group than in normal group
      (79.74 +/- 7.39 micromol/L vs 24.94 +/- 3.38 micromol/L, 2.48 +/- 0.42 micro/mL
      vs 0.82 +/- 0.33 micro/mL, 5.63 +/- 0.85 microg/mL vs 2.01 +/- 0.32 microg/mL
      respectively, P < 0.01), and lower in LPS + Lianshu group than in LPS + berberine
      group (48.59 +/- 4.70 micromol/L vs 51.56 +/- 8.38 micromol/L, 1.43 +/- 0.53
      micromol/mL vs 1.81 +/- 0.42 micromol/mL, 4.00 +/- 0.54 microg/mL vs 4.88 +/-
      0.77 microg/mL respectively, P < 0.05). The morphology of the intestinal mucosa
      showed destroyed villi in LPS group and atrophied intestinal mucosa in other
      groups. The pathological intestinal mucosal changes were less in LPS + Lianshu
      group than in LPS group. The number of IgA+ plasma cells and amount of SIgA were
      higher in LPS + Lianshu group than in LPS group (1.16 +/- 0.19/microm(2) vs 1.09
      +/- 0.28/microm(2), P = 0.026; 0.59 +/- 0.12 mg/L vs 0.15 +/- 0.19 mg/L
      respectively, P = 0.000). Lianshu had counteractive effects on yeast-induced
      pyrexia and enterokinesia in rats. CONCLUSION: Lianshu preparation has
      therapeutic effects on LPS-induced diarrhea and enterokinesia in rats.

PMID- 19399936
TI  - High level of ezrin expression in colorectal cancer tissues is closely related to
      tumor malignancy.
AB  - AIM: To investigate the ezrin expression in normal colorectal mucosa and
      colorectal cancer tissues, and study the correlation between ezrin expression in
      colorectal cancer tissues and tumor invasion and metastasis. METHODS: Eighty
      paraffin-embedded cancer tissue samples were selected from primary colorectal
      adenocarcinoma. Twenty-eight patients had well-differentiated, 22 had moderately
      differentiated and 30 had poorly differentiated adenocarcinoma. Forty-five
      patients and 35 patients had lymph node metastasis. Forty-five patients were of
      Dukes A to B stage, and 35 were of C to D stage. Another 22 paraffin-embedded
      tissue blocks of normal colorectal epithelium (> 5 cm away from the edge of the
      tumor) were selected as the control group. All patients with colorectal cancer
      were treated surgically and diagnosed histologically, without preoperative
      chemotherapy or radiotherapy. The immunohistochemistry was used to detect the
      ezrin expression in paraffin-embedded normal colorectal mucosa tissues and
      colorectal cancer tissue samples. RESULTS: Ezrin expression in colorectal cancer
      was significantly higher than in normal colorectal mucosa (75.00% vs 9.09%, P <
      0.01), and there was a close relationship between ezrin expression and the degree
      of tumor differentiation, lymph node metastasis and Dukes stage (88.46% vs
      50.00%, P < 0.01; 94.28% vs 51.11%, P < 0.01; 94.28% vs 51.11%, P < 0.01).
      CONCLUSION: Ezrin expression is obviously higher in colorectal cancer tissues
      than in normal colorectal mucosa tissues, and the high level of ezrin expression
      is closely related to the colorectal cancer invasion and metastasis process.

PMID- 19399937
TI  - Overexpression of DNA methyltransferase 1 and its biological significance in
      primary hepatocellular carcinoma.
AB  - AIM: To explore the relationship between DNA methyltransferase 1 (DNMT1) and
      hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and its biological
      significance in primary HCC. METHODS: We carried out an immunohistochemical
      examination of DNMT1 in both HCC and paired non-neoplastic liver tissues from
      Chinese subjects. DNMT1 mRNA was further examined in HCC cell lines by real-time
      PCR. We inhibited DNMT1 using siRNA and detected the effect of depletion of DNMT1
      on cell proliferation ability and cell apoptosis in the HCC cell line SMMC-7721.
      RESULTS: DNMT1 protein expression was increased in HCCs compared to
      histologically normal non-neoplastic liver tissues and the incidence of DNMT1
      immunoreactivity in HCCs correlated significantly with poor tumor differentiation
      (P = 0.014). There were more cases with DNMT1 overexpression in HCC with HBV
      (42.85%) than in HCC without HBV (28.57%). However, no significant difference in
      DNMT1 expression was found in HBV-positive and HBV-negative cases in the Chinese
      HCC group. There was a trend that DNMT1 RNA expression increased more in HCC cell
      lines than in pericarcinoma cell lines and normal liver cell lines. In addition,
      we inhibited DNMT1 using siRNA in the SMMC-7721 HCC cell line and found depletion
      of DNMT1 suppressed cells growth independent of expression of proliferating cell
      nuclear antigen (PCNA), even in HCC cell lines where DNMT1 was stably decreased.
      CONCLUSION: The findings implied that DNMT1 plays a key role in HBV-related
      hepatocellular tumorigenesis. Depletion of DNMT1 mediates growth suppression in
      SMMC-7721 cells.

PMID- 19399938
TI  - Synchronous incidental gastrointestinal stromal and epithelial malignant tumors.
AB  - AIM: To investigate the incidence of incidental gastrointestinal stromal tumor
      (GIST) and its etiopathogenesis. METHODS: From January 1, 2000 to December 31,
      2007, 13804 cases of gastrointestinal epithelial malignant tumor (EMT) and 521
      cases of pancreatic adenocarcinoma (PAC) were successfully treated with surgery
      at the Department of General Surgery and the Department of Thoracic Surgery, West
      China Hospital, Sichuan University, China. The clinical and pathologic data of
      311 cases of primary GIST, including 257 cases with clinical GIST and 54 cases of
      incidental GIST were analyzed. RESULTS: Of the 311 patients, 54 had incidental
      GIST, accounting for 17.4%. Of these tumors, 27 were found in 1.13% patients with
      esophageal squamous cell carcinoma (ESCC), 22 in 0.53% patients with gastric
      adenocarcinoma (GAC), 2 in 0.38% patients with PAC, 2 in 0.03% patients with
      colorectal adenocarcinoma, and 1 in one patient with GAC accompanying ESCC,
      respectively. Patients with incidental GIST presented symptoms indistinguishable
      from those with EMT. All incidental GIST lesions were small in size, and the
      majority had a low mitotic activity while only 1.9% (5/257) of clinical GIST
      lesions had a high risk. CONCLUSION: Incidental GIST may occur synchronously with
      other tumors and has a high prevalence in males. Surgery is its best treatment
      modality.

PMID- 19399939
TI  - Effect of 5-FU on modulation of disarrangement of immune-associated cytokines in
      experimental acute pancreatitis.
AB  - AIM: To investigate the effects of 5-Fluorouracil (5-FU) on modulation of pro
      inflammatory and anti-inflammatory cytokines in acute pancreatitis and the
      mechanism of it in the treatment of acute pancreatitis. METHODS: Male Sprague
      Dawley rats were assigned to 3 Groups: Group A, sham operated rats as controls (n
      = 7); Group B, acute pancreatitis induced by ductal injection with 5% sodium
      cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the
      pancreatitis was induced as in Group B, the rats were injected intravenously with
      5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after
      operation (n = 7), and blood samples were taken for measurement of tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) (by
      bioassay), and interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta)
      (by ELISA). The wet weight of pancreatic tissue, serum amylase levels and white
      blood cells were also measured. RESULTS: Four rats in Group B and one in Group C
      died after pancreatitis was induced. Both pro-inflammatory cytokines (TNF-alpha,
      IL-1, IL-6) at the 2 and 6 h period and the anti-inflammatory cytokines (IL-10,
      TGF-beta) at 24 h increased significantly (P < 0.05) in rats of Group B. After
      treatment with 5-FU, TNF-alpha, IL-1, and IL-6 in serum of rats of Group C were
      inhibited at 2 and 6 h after operation (P < 0.05), and IL-10, TGF-beta were
      inhibited at 24 h compared to Group B (P < 0.05). Obvious improvements in the
      severity of the acute pancreatitis, including the amylase levels, wet weight of
      pancreatic tissue and neutrophil counts, were also observed after treatment with
      5-FU. CONCLUSION: 5-FU is an anti-metabolic and immunosuppressive agent which can
      minimize the abnormal immune cytokine response and relieve the pathophysiological
      disorders associated with experimental acute pancreatitis.

PMID- 19399940
TI  - Hepatic failure caused by plasma cell infiltration in multiple myeloma.
AB  - Although plasma cell infiltration is not rare in autopsy of patients with
      multiple myeloma (MM), it is very rarely detected in living patients. This is
      because MM rarely causes significant liver dysfunction that requires further
      evaluation. A 49-year-old man presented with acute renal failure and was
      diagnosed with kappa light chain MM stage IIB. Thalidomide and dexamethasone were
      initiated. The patient developed a continuous increase in bilirubin that led to
      severe cholestasis. A liver biopsy revealed plasma cell infiltration. He then
      rapidly progressed to liver failure and died. Treatment options are limited in MM
      with significant liver dysfunction. Despite new drug therapies in MM, those
      patients with rapidly progressive liver failure appear to have a dismal outcome.

PMID- 19399941
TI  - Chemical ablation of the gallbladder using alcohol in cholecystitis after
      palliative biliary stenting.
AB  - Chemical ablation of the gallbladder is effective in patients at high risk of
      complications after surgery. Percutaneous gallbladder drainage is an effective
      treatment for cholecystitis; however, when the drain tube cannot be removed
      because of recurrent symptoms, retaining it can cause problems. An 82-year-old
      woman presented with cholecystitis and cholangitis caused by biliary stent
      occlusion and suspected tumor invasion of the cystic duct. We present successful
      chemical ablation of the gallbladder using pure alcohol, through a percutaneous
      gallbladder drainage tube, in a patient who developed intractable cholecystitis
      with obstruction of the cystic duct after receiving a biliary stent. Our results
      suggest that chemical ablation therapy is an effective alternative to surgical
      therapy for intractable cholecystitis.

PMID- 19399942
TI  - 7th revision of the Declaration of Helsinki: good news for the transparency of
      clinical trials.

PMID- 19399943
TI  - Centralized national ethical review of clinical trials in Croatia.
AB  - AIM: To present the Croatian system of ethical review of clinical trials and
      assessment outcomes of the applications reviewed by the Croatian Central Ethics
      Committee. METHODS: Clinical trial applications reviewed by the Croatian Central
      Ethics Committee, which has the legal mandate to review clinical trials of
      medicinal products and medical devices, were retrospectively analyzed from May
      2004 to the end of 2008 according to the number, research area, and type of
      opinion issued. Applications from 2008 were analyzed separately according to the
      study phase, participants (adult trials vs pediatric trials), and sponsor
      (commercial trials vs academic trials). Data were analyzed by descriptive
      statistics. RESULTS: Since its establishment in 2004, the Croatian Central Ethics
      Committee has reviewed 407 trials. The greatest number of clinical trials was in
      the field of oncology (n = 69), mental and behavioral disorders (n = 52), and
      endocrine, nutritional, and metabolic diseases (n = 50). In the initial
      assessment of clinical trials, 60% applications received a conditionally positive
      opinion. In 28% of applications, the opinion had to be postponed because
      additional documentation or explanations were required. In 2008, the Croatian
      Central Ethics Committee reviewed 99 trials, most of which were phase III trials
      (n = 57). Five clinical trials included pediatric population and 3 were academic
      clinical trials. CONCLUSION: The model of centralized clinical trial review seems
      to be appropriate for the current number of clinical trials conducted in Croatia.
      The efficient and standardized review process of clinical trials by the Central
      Ethics Committee may positively affect the increasing number of clinical trials
      conducted in Croatia. Future development includes the transparency of the
      clinical trials through a publically available database and establishing the
      basis for conducting academic clinical trials.

PMID- 19399944
TI  - Association of estrogen receptor alpha gene polymorphisms with cytokine genes
      expression in systemic lupus erythematosus.
AB  - AIM: To analyze the association of estrogen receptor alpha (OR alpha) gene
      polymorphisms with cytokine genes expression in patients with systemic lupus
      erythematosus (SLE) and controls. METHODS: Genomic DNA was extracted and
      polymorphisms of XbaI, Ukrainian (XX, Xx, or xx genotype) and PvuII (PP, Pp, or
      pp) in intron 1 of OR alpha gene were detected by polymerase chain reaction
      restriction fragment length polymorphisms (PCR-RFLP) method. The messenger RNA
      (mRNA) levels of interleukin (IL)-10, IL-4, interferon (IFN)-gamma, and IL-2 were
      assessed by semiquantitative reverse transcription polymerase chain reaction (RT
      PCR). RESULTS: In patients with SLE with PpXx genotype, IL-10 and IL-4 mRNA
      expression was higher (P < 0.001 and P = 0.013, respectively), while in patients
      with SLE with Ppxx genotype IFN-gamma and IL-2 mRNA expression was lower than in
      controls (P < 0.001). There was no significant difference in mRNA expression of 4
      cytokines among controls with various genotypes. CONCLUSION: OR alpha gene
      polymorphism may be associated with the expression of IL-10, IL-4, IL-2, and IFN
      gamma in patients with SLE.

PMID- 19399945
TI  - Serum antibodies positivity to 12 Helicobacter pylori virulence antigens in
      patients with benign or malignant gastroduodenal diseases--cross-sectional study.
AB  - AIM: To investigate the association of gastric histological and endoscopic
      findings in patients with Helicobacter pylori (H. pylori), according to presence
      of seropositivity to 12 bacterial virulence antigens. METHODS: This is a cross
      sectional single-center study of 360 consecutive outpatients referred in the
      period of one year to upper gastrointestinal endoscopy because of dyspeptic
      complaints. Patients sera were tested by Western blot method to determine the
      presence of serum antibodies to bacterial virulence antigens--p120 (CagA-
      cytotoxin-associated antigen), p95 (VacA - vacuolating cytotoxin), p67 (FSH-
      flagellar sheath protein), p66 (UreB--urease enzyme heavy subunit), p57 (HSP
      homologue--heath shock protein homologue), p54 (flagellin), p33, p30 (OMP--outer
      membrane protein), p29 (UreA--urease enzyme light subunit), p26, p19, and p17.
      Upper gastrointestinal endoscopy was performed, endoscopic diagnosis recorded,
      and 4 mucosal biopsy samples were obtained and assessed according to Updated
      Sydney protocol. RESULTS: The sera of 207 patients were analyzed. Thirty patients
      had gastric adenocarcinoma, 126 peptic ulcers, and 51 normal finding. p120 (CagA)
      seropositivity was significantly more often present in patients with higher
      activity grade in the antrum (P = 0.025), p30 in patients with greater
      inflammation in the antrum (P = 0.025) and the corpus (P = 0.010), p33 in
      patients with greater inflammation in the corpus (P = 0.050), and p19 (OMP) in
      patients with lower intestinal metaplasia grades in the corpus (P = 0.025).
      Seroreactivity to all other bacterial proteins showed no association with the
      histological status of the stomach mucosa. Except for the seropositivity to
      protein p95 (VacA), which was more often present in patients with duodenal ulcer
      (P = 0.006), there was no difference in seroreactivity to other bacterial
      proteins and upper gastrointestinal endoscopic findings. CONCLUSIONS: p120
      (CagA), p33, p30 (OMP), and p19 (OMP) seropositivity was more often present in
      patients with higher grades of the histological parameters of gastritis and
      seropositivity to protein p95 (VacA) with endoscopic presence of duodenal ulcer.
      Histological parameters of gastritis are more associated with bacterial virulence
      than endoscopic findings.

PMID- 19399946
TI  - Combination of quantitative capnometry, N-terminal pro-brain natriuretic peptide,
      and clinical assessment in differentiating acute heart failure from pulmonary
      disease as cause of acute dyspnea in pre-hospital emergency setting: study of
      diagnostic accuracy.
AB  - AIM: To determine the diagnostic accuracy of the combination of quantitative
      capnometry (QC), N-terminal pro-brain natriuretic peptide (NT-proBNP), and
      clinical assessment in differentiating heart failure (HF)-related acute dyspnea
      from pulmonary-related acute dyspnea in a pre-hospital setting. METHODS: This
      prospective study was performed in the Center for Emergency Medicine Maribor,
      Slovenia, January 2005-June 2007. Two groups of patients with acute dyspnea apnea
      were compared: HF-related acute dyspnea group (n = 238) vs pulmonary-related
      acute dyspnea (asthma/COPD) group (n = 203). The primary outcome was the
      comparison of combination of QC, NT-proBNP, and clinical assessment vs NT-proBNP
      alone or NT-proBNP in combination with clinical assessment, in differentiating HF
      related acute dyspnea from pulmonary-related acute dyspnea (asthma/COPD) in pre
      hospital emergency setting, using the area under the receiver operating
      characteristic curve (AUROC). The secondary outcomes end points were
      identification of independent predictors for final diagnosis of acute dyspnea
      (caused by acute HF or pulmonary diseases), and determination of NT-proBNP
      levels, as well as capnometry, in the subgroup of patients with a previous
      history of HF and in the subgroup of patients with a previous history of
      pulmonary disease. RESULTS: In differentiating between cardiac and respiratory
      causes of acute dyspnea in pre-hospital emergency setting, NT-proBNP in
      combination with PetCO2 and clinical assessment (AUROC, 0.97; 95% confidence
      interval [CI], 0.90-0.99) was superior to combination of NT-proBNP and clinical
      assessment (AUROC, 0.94; 95% CI, 0.88-0.96; P = 0.006) or NT-proBNP alone (AUROC,
      0.90; 95% CI, 0.85-0.94; P = 0.005). The values of NT-proBNP> or = 2000 pg/mL and
      PetCO2 < or = 4 kPa were strong independent predictors for acute HF. In the group
      of acute HF dyspneic patients, subgroup of patients with previous COPD/asthma had
      significantly higher PetCO2 (3.8 +/- 1.2 vs 5.8 +/- 1.3 kPa, P = 0.009). In the
      group of COPD/asthma dyspneic patients, NT-proBNP was significantly higher in the
      subgroup of patients with previous HF (1453.3 +/- 552.3 vs 741.5 +/- 435.5 pg/mL,
      P = 0.010). CONCLUSION: In differentiating between cardiac and respiratory causes
      of acute dyspnea in pre-hospital emergency setting, NT-proBNP in combination with
      capnometry and clinical assessment was superior to NT-proBNP alone or NT-proBNP
      in combination with clinical assessment.

PMID- 19399948
TI  - Alcohol intoxication in pediatric age: ten-year retrospective study.
AB  - AIM: To examine the changes in the number of children younger than 18 who were
      hospitalized due to alcohol intoxication at the Department of Pediatrics,
      University Hospital of Split, from November 1, 1997 to October 31, 2007. METHODS:
      Data on children hospitalized due to intoxication were retrieved from hospital
      medical records. Children were classified into 4 age groups: 0-5, 6-9, 10-13, and
      14-18 years, and their sex and type of intoxication were recorded. For children
      with alcohol intoxication, data on time of intoxication, reason for drinking,
      presence of injuries or suspected suicide attempts, and possible presence of
      other drugs in the organism were collected. RESULTS: Out of 29 506 hospitalized
      children, 594 were hospitalized due to intoxications. Out of these, 239 (40.2%)
      were hospitalized due to intoxication by alcohol. More boys than girls were
      hospitalized (71.1%). The proportion of alcohol intoxication cases among all
      types of intoxication cases increased from 16.7% in 1997/98 to 66.3% in 2006/07.
      The proportion of patients hospitalized due to alcohol intoxication increased
      from 0.3% of all hospitalized children in the first year to 1.7% in the last year
      of the study (P = 0.015, z test for comparison of two proportions). Eighty two
      per cent of cases alcohol intoxication were in the 14-18 age-group. The number of
      alcohol intoxication cases increased among girls from 1 case (6.3% of all
      intoxication cases among girls) in 1997/98 to 15 cases (45.5%) in 2006/07, while
      among boys it increased from 6 cases (23.1% of all intoxicated boys) in 1997/98
      to 44 cases (78.6%) in 2006/07. Children usually drank outside their homes
      (79.4%) and mostly on weekends and holidays (73.2%). CONCLUSION: The alarming
      increase in the number of hospitalizations due to alcohol intoxication in
      children, especially among girls and in the adolescent age group, represents a
      serious problem, which requires further attention and research.

PMID- 19399947
TI  - Silencing of heat shock protein 70 expression enhances radiotherapy efficacy and
      inhibits cell invasion in endometrial cancer cell line.
AB  - AIM: To investigate the role of heat shock proteins 70 (HSP70) in
      radiosensitivity and invasiveness of endometrial cancer in vitro. METHODS: HSP70
      expression was silenced in relatively radioresistant, well-differentiated human
      endometrial cancer cell line ISK, using small interference RNA method, or by
      HSP70 overexpression after transfecting a HSP70-expressing vector. The effect of
      HSP70 on ISK cell line response to irradiation was evaluated. The surviving
      fraction was measured using colony-formation assay. Apoptosis was detected by
      flow cytometry and HSP70 expression was determined by quantitative real-time
      polymerase chain reaction, western-blot, and/or immunocytochemistry. Cell
      invasiveness was measured using transwell invasion assay. RESULTS: HSP70
      silencing caused a significant increase in irradiation-induced cell killing in
      comparison with control cells, with an enhancement factor of 1.27, and in the
      percentage of apoptotic cells (14.22% vs 6.74%, P = 0.021). After 4 Gy
      irradiation, mean +/- standard deviation survival fraction in ISK cells was
      reduced to 0.32 +/- 0.04 in comparison with control values but in ISK/siRNA-HSP70
      cells the survival fraction was higher and amounted to 0.51 +/- 0.08 (P = 0.026).
      Silencing HSP70 significantly inhibited cell invasion before and after
      irradiation (106 +/- 19 vs 219 +/- 18 and 119 +/- 16 vs 256 +/- 31, P = 0.007).
      On the contrary, ectopic overexpression of HSP70 attenuated irradiation-induced
      apoptosis (7.15% vs 4.08%, P = 0.043) and induced more ISK/HSP70 cells invaded
      through the filters than mock-infected cells before and after irradiation (274 +/
      21 vs 194 +/- 16 before irradiation, and 298 +/- 24 vs 227 +/- 19 after
      irradiation, respectively, P = 0.032). CONCLUSION: Disruption of HSP70-induced
      cytoprotection during irradiation enhances therapeutic effect of irradiation,
      which makes HSP70 a promising target in the research of endometrial cancer.

PMID- 19399949
TI  - Perceived exposure to substance use and risk-taking behavior in early
      adolescence: cross-sectional study.
AB  - AIM: To examine the relation between perceived exposure to parents, siblings, and
      peers' substance use and self-reported substance consumption among early
      adolescents in Primorsko-goranska county, Croatia, and between perceived exposure
      to substance use and risk-taking behaviors such as going out late at night,
      gathering at secluded places, skipping school, and gambling. METHOD: A self
      reported cross-sectional survey was conducted in 2007 among 2219 eight-grade (14
      year old) pupils in elementary schools in Primorsko-goranska county. Exposure to
      substance use in their immediate social environment, self-reported consumption of
      cigarettes, alcohol, inhalants, and marihuana, ways of spending free time, and
      family and peer relationships were assessed. RESULTS: There was a significant
      association between perceived exposure to substance use and self-reported
      consumption of cigarettes, alcohol, inhalants, and marihuana in both sexes (P <
      0.001). Pupils whose parents, siblings, and peers used substances significantly
      more often developed the same behavioral patterns. Level of exposure to substance
      use in the immediate social environment had the strongest effect on experimenting
      with smoking among girls (from 26.6% in low exposure to 76.2% in high exposure
      group) and among boys (from 15.8% in low exposure to 69.4% in high exposure); on
      regular everyday smoking among girls (from 4.4% in low exposure to 45% in high
      exposure group) and among boys (from 2.7% in low exposure to 36.7% in high
      exposure group); on hard liquor consumption among girls (from 25.1% in low
      exposure to 79.5% in high exposure group) and among boys (from 28.1% in low
      exposure to 78.4% in high exposure group), as well as on binge drinking among
      girls (from 10.9% in low exposure to 56.6% in high exposure group) and among boys
      (from 15.5% in low exposure to 62.4% in high exposure group). Girls and boys
      exposed to substance use engaged more often in risk-taking and potentially
      delinquent behaviors (F(2, 1180) = 166 502; P < 0.001, two-way ANOVA).
      CONCLUSION: High exposure to substance use in immediate social environment and
      its great impact on substance use among early adolescents indicate that there is
      a need for the introduction of preventive programs that would reduce
      inappropriate behavior among adolescents' social models.

PMID- 19399950
TI  - Physical activity of Croatian population: cross-sectional study using
      International Physical Activity Questionnaire.
AB  - AIM: To determine the physical activity level of the Croatian population in
      different domains of everyday life. METHODS: A random stratified sample of 1032
      Croatians aged 15 years and older was interviewed using the official Croatian
      long version of the International Physical Activity Questionnaire (IPAQ). Total
      physical activity and physical activity in each of the 4 life domains--work,
      transport, domestic and garden, and leisure-time--were estimated. Physical
      activity was expressed as metabolic equivalent-hours per week (MET-hour/week).
      RESULTS: Median total physical activity for the whole sample was 58.2 MET
      hour/week. Median physical activity in MET-hour/week was 30.4 for work, 5.0 for
      transportation, 13.1 for domestic and garden, and 6.0 for leisure-time domain.
      The lowest physical activity was found in the 15-24 age group (42.7 MET
      hour/week) and the highest in the 55-64 age group (72.0 MET-hour/week). Multiple
      regression analysis showed a significant relationship of socio-demographic and
      health-related characteristics (size of settlements, household income,
      educational level, age, body mass index, self-rated physical health, and self
      rated mental health) with physical activity in all domains (P < 0.001).
      CONCLUSION: Studies on physical activity in transition countries should include
      the domains of work and domestic and garden, since if only leisure-time domain is
      examined, the total physical activity level could be underestimated. As the
      lowest physical activity was reported by adolescents and young adults, strategies
      for increasing physical activity in this age group should be developed.

PMID- 19399951
TI  - Educating adolescents about healthy sleep: experimental study of effectiveness of
      educational leaflet.
AB  - AIM: To evaluate how exposure to educational leaflet about healthy sleep affects
      knowledge about sleep in adolescents. METHODS: The study included students aged
      15-18 years from 12 high schools (1209 participants; 85% of eligible study
      population). Multistage sampling was used and the selected schools were randomly
      assigned into two intervention groups and two control groups, according to the
      Solomon experimental design. Intervention groups received educational leaflets
      and control groups did not. In one of the intervention groups and one of the
      control groups, pre-testing of knowledge about sleep was performed. Students
      answered the Sleep Knowledge Test, which was constructed in accordance with the
      information on the leaflet. Data were analyzed by four-way ANOVA and additional
      analyses of simple main effects were performed. RESULTS: Positive effect of
      educational leaflet was found in students aged 15 (F = 28.46; P < 0.001), 16 (F =
      5.74; P = 0.017), and 17 (F = 17.17; P < 0.001), but there was no effect in
      students aged 18 (P = 0.467). In male students, positive effect of the leaflet
      was found only in the group that had not been pre-tested (F = 6.29; P = 0.012),
      while in female students, it was found in both pre-tested (F = 26.24; P < 0.001)
      and not pre-tested group (F = 17.36; P < 0.001), with greater effect in pre
      tested group (F = 5.70; P = 0.017). Female students generally showed better
      knowledge about sleep than male students (F = 95.95; P < 0.001). CONCLUSION:
      Educational leaflets can be an effective first step in educating younger high
      school students about healthy sleep, with the method being more effective in
      female adolescents.

PMID- 19399953
TI  - Successes and challenges of Malawi's only medical school.

PMID- 19399952
TI  - Quality of life after stroke in old age: comparison of persons living in nursing
      home and those living in their own home.
AB  - AIM: To determine the differences in subjective quality of life between elderly
      people living in a nursing home and those living in their own homes after brain
      stroke, and to determine the contribution of demographic variables and different
      quality of life domains to the explanation of self-assessed quality of life.
      METHODS: The study included 60 elderly men and women, 30 living in their own
      homes (median age, 81; range, 72-90) and 30 living in a nursing home (median age,
      81; range, 72-86). Both groups received care (stationary or ambulatory) from the
      same nursing home. World Health Organization Quality of Life Questionnaire-short
      version, self-assessed quality of life questionnaire, and demographic
      questionnaire were used to collect data on subjective quality of life. The
      participants completed self-report questionnaires individually. RESULTS: Quality
      of life scores were significantly higher in the elderly living in a nursing home
      than in the elderly living in their own home (mean +/- standard deviation, 78.7
      +/- 12.8 vs 59.3 +/- 17.3 out of maximum 100, P < 0.001). Also, the elderly
      living in the nursing home scored significantly higher than those living in their
      own home on all 4 quality of life domains (maximum 100 for each domain): physical
      (28.5 +/- 3.3 vs 17.2 +/- 5.0), psychological (22.3 +/- 3.7 vs 16.3 +/- 5.0),
      social relationships (11.4 +/- 1.6 vs 8.3 +/- 1.7), and environment (32.8 +/- 4.6
      vs 24.0 +/- 6.1) domain (P < 0.001 for all). All predictive variables together
      explained 51.9% of quality of life variance, with self-assessed health being the
      most significant predictor. CONCLUSION: Quality of life of the elderly in a
      nursing home was significantly higher than that of their peers living in their
      own home, which may be related to better care in specially organized settings.

PMID- 19399954
TI  - If Leonardo was alive today (and looking for a job).

PMID- 19399955
TI  - Revolution or reformation.

PMID- 19399956
TI  - Group-based trust in strangers: the role of stereotypes and expectations.
AB  - Across two studies, we provide evidence for group-based trust in strangers.
      Specifically, when we offered participants a choice between an unknown monetary
      allocation made by an in-group (university or major) or an out-group allocator,
      both of whom had total control over the distribution of an identical sum of
      money, participants strongly preferred the in-group allocator. This preference
      occurred regardless of whether the stereotype of the in-group was relatively more
      positive or more negative than that of the out-group. However, this preference
      did not persist when participants believed that the allocator was unaware of
      their group membership. Measures of expected share of the allocator's funds
      support our hypothesis that differential trust of in-group members results from
      expectations of altruistic and fair behavior toward fellow in-group members
      rather than from positive stereotypes of the in-group.

PMID- 19399957
TI  - Translational cancer research in Europe.

PMID- 19399958
TI  - Translational cancer research in the USA.

PMID- 19399959
TI  - Cancer research funding in USA.

PMID- 19399960
TI  - Cancer research funding in Europe.

PMID- 19399961
TI  - Cancer research funding in Asia.

PMID- 19399962
TI  - Current world literature. Ethics, economics and outcome.

PMID- 19399963
TI  - Current world literature. Trauma and transfusion.

PMID- 19399964
TI  - Mechanisms and results of the antibody-dependent enhancement  of viral infections
      and role in the pathogenesis  of coxsackievirus B-induced diseases.
AB  - The mechanisms of the antibody-dependent enhancement (ADE) of viral infection are
      presented, particularly within the Picornaviridae family. The ADE of infection
      has been described in both human and animal models, worsens viral infections and
      compromises vaccine safety. The ADE of coxsackievirus B infection can also be
      implied in the pathogenesis of diseases like chronic dilated cardiomyopathy or
      insulin-dependent type 1 diabetes.

PMID- 19399965
TI  - Pneumococcal pneumonia: clinical features, diagnosis and  management in HIV
      infected and HIV noninfected patients.
AB  - PURPOSE OF REVIEW: In this review, we focus on the clinical features, diagnosis
      and management of pneumococcal pneumonia in HIV-infected and noninfected
      patients, with particular attention to the most recent advances in this area.
      RECENT FINDINGS: Classical clinical features are found in young adults, whereas
      atypical forms occur in immunocompromised patients including HIV-infected
      individuals. Bacteremic pneumococcal pneumonia is more frequently observed in HIV
      infected and also in low-risk patients, according to the Pneumonia Severity Index
      (PSI). Pneumococcal pneumonia diagnostic process includes physical examination,
      radiologic findings and microbiologic diagnosis. However, etiologic diagnosis
      using traditional culture methods is difficult to obtain. In this setting,
      urinary antigen test, which recognizes Streptococcus pneumoniae cell wall C
      polysaccharide, increases the probability of etiologic diagnosis. A correct
      management approach is crucial in reducing pneumococcal pneumonia mortality. The
      use of the PSI helps clinicians in deciding between inpatient and outpatient
      management in immunocompetent individuals, according to Infectious Diseases
      Society of America (IDSA)-American Thoracic Society (ATS) guidelines. Recent
      findings support PSI utility also in HIV-infected patients. Recently, efficacy of
      pneumococcal vaccine in reducing pneumococcal disease incidence has been
      evidenced in both HIV-infected and noninfected individuals. SUMMARY: Rapid
      diagnosis and correct management together with implementation of preventive
      measures are crucial in order to reduce pneumococcal pneumonia related incidence
      and mortality in HIV-infected and noninfected patients.

PMID- 19399966
TI  - Effectiveness of gerontologically informed nursing assessment and  referral
      interventions for older persons attending the emergency  department: systematic
      review.
AB  - AIM: This paper is a report of a literature review conducted to analyse data from
      published studies reporting nursing interventions targeted at older attendees of
      emergency departments (EDs), and to provide a critical appraisal of the evidence
      concerning their effectiveness. BACKGROUND: Attendance at hospital EDs by older
      persons presents opportunities for targeted interventions to address actual and
      potential problems associated with or in addition to the presenting problem. The
      evidence concerning the effectiveness of such interventions is mixed. DATA
      SOURCES: Studies were retrieved from a systematic search of published works
      indexed in CINAHL, MEDLINE (PubMed), Science Direct and the Cochrane Central
      Register of Controlled Trials (CENTRAL). METHODS: A systematic review of
      effectiveness was conducted using the Cochrane Effective Practice and
      Organisation of Care guidelines and a narrative synthesis approach for data
      handling and presentation. The review period was 1992 to 31 August 2008. RESULTS:
      Nursing assessment and referral interventions have demonstrated effectiveness in
      reducing service use and improving physical function, but have failed to
      demonstrate statistically significant effects on predicted patient and/or health
      systems outcomes. CONCLUSION: The evidence of the effectiveness of
      gerontologically informed nursing assessment and referral interventions in EDs
      must be accepted with caution, as not all studies demonstrated effectiveness in
      predicted patient and/or health systems outcomes, and the testing of complex
      social interventions in randomized clinical trials is inherently problematic.
      Further evidence of the effectiveness of nursing interventions is required, and
      such evidence might be usefully demonstrated using pragmatic, as opposed to
      explanatory, trials.

PMID- 19399967
TI  - Population genetics of Leishmania infantum in Israel and the Palestinian 
      Authority through microsatellite analysis.
AB  - Multilocus microsatellite typing (MLMT) was used to investigate the genetic
      variation among 44 Israeli and Palestinian strains of L. infantum isolated from
      infected dogs and human cases to determine their population structure and to
      compare them with strains isolated from different European countries. Most of the
      Israeli and Palestinian strains had their own individual MLMT profiles; a few
      shared the same profile. A Bayesian model-based approach and phylogenetic
      reconstructions based on genetic distances inferred two main populations that
      were significantly different from the European strains: population A, containing
      16 strains from places in the West Bank and 11 strains from central Israel;and
      population B, containing 7 strains from northern Israel, 9 from central Israel,
      and one Palestinian strain from the Jenin District.Geographically distributed sub
      populations were detected within population B. These results demonstrate similar
      disease dynamics in Israel and the Palestinian Authority. The re-emergence of VL
      in the case of population A is more likely owing to increased dog and human
      contact with sylvatic cycles of parasitic infection rather than to recent
      introduction from the older foci of northern Israel. The latter scenario could be
      true for population B found in few foci of Central Israel.

PMID- 19399968
TI  - Eminence, IQ, physical and mental health, and achievement domain : Cox's 282
      Geniuses revisited.
AB  - Catharine Cox published two studies of highly eminent creators and leaders, the
      first in 1926 as the second volume of Terman's landmark Genetic Studies of Genius
      and the second in 1936 as a coauthored article. The former publication
      concentrated on the relation between IQ and achieved eminence, and the latter
      focused on early physical and mental health. Taking advantage of unpublished data
      from the second study, we examined, for the first time, the relationships among
      achieved eminence, IQ, early physical and mental health, and achievement domain.
      The correlation and regression analyses showed, for these 282 individuals, that
      eminence is a positive function of IQ and that IQ is a positive function of
      mental health and a negative function of physical health, implying an indirect
      effect of physical and mental health on eminence. Furthermore, levels of early
      physical and mental health vary across 10 specific domains of achievement.

PMID- 19399969
TI  - Protocolized vs. non-protocolized weaning for reducing the duration of  
      mechanical ventilation in critically ill adult patients: Cochrane review  
      protocol.
AB  - AIM: This paper is a report of the protocol for a review to identify, critically
      appraise and synthesize the best current evidence supporting the use of weaning
      protocols compared to non-protocolized practice in liberating patients from
      mechanical ventilation. BACKGROUND: Patients experiencing difficulty in weaning
      require a longer hospital stay and have higher morbidity and mortality.
      Consequently, efforts to reduce weaning time are desirable to reduce the duration
      of ventilation and related complications. Standardized weaning protocols are safe
      and effective in reducing the time spent on mechanical
      ventilation.Notwithstanding, the evidence supporting their use in practice is
      inconsistent. The discordant results of studies may reflect the fact that
      protocols vary in composition and are implemented in different environments by
      various healthcare providers. DESIGN: The objectives of this review are to
      compare the total duration of mechanical ventilation between patients weaned
      using protocols vs. non-protocolized practice; to ascertain differences between
      protocolized and non-protocolized weaning with regards to mortality, adverse
      events, quality of life, weaning duration, ICU and hospital stay; and to explore
      variation in outcomes by the type of ICU, the type of protocol and approach to
      delivering the protocol. We will search the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL, ISI
      Web of Science and LILACS. In addition, we will endeavour to identify unpublished
      data and contact first authors of studies included in the review to obtain
      information on unpublished studies or work in progress. CONCLUSION: This review
      will provide much needed direction for healthcare professionals in intensive care
      in terms of both research and practice.

PMID- 19399970
TI  - Predictive eye movements are driven by goals, not by the mirror neuron system.

PMID- 19399971
TI  - Ambiguous group membership is extracted automatically from faces.

PMID- 19399972
TI  - Is multiculturalism or color blindness better for minorities?

PMID- 19399973
TI  - Chronic sorrow in parents of children with type 1 diabetes.
AB  - AIM: This paper reports on a study exploring parents' longer-term experiences of
      having a child with type 1 diabetes. BACKGROUND: Parents of children with type 1
      diabetes may experience a grief reaction at diagnosis similar to that normally
      associated with bereavement, but little is known about their long-term emotional
      adaptation. Chronic sorrow, a sustained but intermittent grief reaction, is
      identified in adults with diabetes but has not previously been explored in
      relation to parents. METHODOLOGY: In-depth interviews were conducted in 2007 with
      a convenience sample of 17 parents of children with type 1 diabetes 7-10 years
      after diagnosis. Data were explored within a theoretical framework of grief,
      loss, adaptation, and change. FINDINGS: Parents had adapted to the needs of
      diabetes management but most had not 'come to terms' with the diagnosis. They
      experienced a resurgence of grief at critical times during their child's
      development and some, particularly mothers, became upset during their interviews,
      even though these took place 7-10 years after their child's diagnosis. Mothers
      elaborated more on their emotions than fathers, but continuing feelings
      associated with grief, such as anger and guilt, were expressed by both fathers
      and mothers. CONCLUSION: Greater understanding of parents' long-term emotional
      responses and recognition that grief may never resolve in these parents may
      enable healthcare professionals to provide appropriate and timely support at
      critical times.

PMID- 19399974
TI  - Not all visual expertise is holistic, but it may be leftist: the case of Chinese
      character recognition.
AB  - We examined whether two purportedly face-specific effects, holistic processing
      and the left-side bias, can also be observed in expert-level processing of
      Chinese characters, which are logographic and share many properties with faces.
      Non-Chinese readers (novices) perceived these characters more holistically than
      Chinese readers (experts). Chinese readers had a better awareness of the
      components of characters, which were not clearly separable to novices. This
      finding suggests that holistic processing is not a marker of general visual
      expertise; rather, holistic processing depends on the features of the stimuli and
      the tasks typically performed on them. In contrast, results for the left-side
      bias were similar to those obtained in studies of face perception. Chinese
      readers exhibited a left-side bias in the perception of mirror-symmetric
      characters, whereas novices did not; this effect was also reflected in eye
      fixations. Thus, the left-side bias may be a marker of visual expertise.

PMID- 19399975
TI  - Providing psychosocial and physical rehabilitation advice for patients   with
      burns.
AB  - AIM: This paper is a report of a study evaluating the perceived skills of nursing
      and allied healthcare professionals in providing psychosocial and physical
      rehabilitation advice, including the effect of years of burn injury experience.
      BACKGROUND: Recovery from burn injuries is a complex mix of physical and
      psychosocial rehabilitation, yet research in the UK has demonstrated that
      healthcare professionals feel more competent at giving advice to patients on
      issues of physical rehabilitation than psychosocial rehabilitation. METHODS: This
      was a replication study with a cross-sectional design. A questionnaire survey was
      conducted with a convenience sample of healthcare professionals in a large urban
      hospital with specialist burn and plastic services in New Zealand. The data were
      collected in 2005. RESULTS: Consistent with the UK results, New Zealand
      healthcare professionals rated their skills in advising patients about physical
      items of burn rehabilitation higher than their skills for psychosocial items.
      Years of experience working with burns was related to greater perceived skill in
      advising patients on physical rehabilitation. In contrast, no relationship
      between years of experience and perceived skill in the provision of psychosocial
      rehabilitation advice was found. CONCLUSION: Strategies to enhance effective
      staff/patient communication should form an integral part of staff education. The
      psychosocial needs of patients must be incorporated as an essential part of such
      strategies.

PMID- 19399976
TI  - The briefest of glances: the time course of natural scene understanding.
AB  - What information is available from a brief glance at a novel scene? Although
      previous efforts to answer this question have focused on scene categorization or
      object detection, real-world scenes contain a wealth of information whose
      perceptual availability has yet to be explored. We compared image exposure
      thresholds in several tasks involving basic-level categorization or global-
      property classification. All thresholds were remarkably short: Observers achieved
      75%-correct performance with presentations ranging from 19 to 67 ms, reaching
      maximum performance at about 100 ms. Global-property categorization was performed
      with significantly less presentation time than basic-level categorization, which
      suggests that there exists a time during early visual processing when a scene may
      be classified as, for example, a large space or navigable, but not yet as a
      mountain or lake. Comparing the relative availability of visual information
      reveals bottlenecks in the accumulation of meaning. Understanding these
      bottlenecks provides critical insight into the computations underlying rapid
      visual understanding.

PMID- 19399977
TI  - Career trajectories of nurses leaving the hospital sector in Ontario,  Canada
      (1993-2004).
AB  - AIM: This paper is a report of an analysis of the career trajectories of nurses 1
      year after leaving hospitals. BACKGROUND: Although hospitals are traditionally
      the largest employers of nurses, technological advances and budgetary constraints
      have resulted in many countries in relative shrinkage of the hospital sector and
      a shift of care (and jobs) into home/community settings. It has been often
      assumed that nurses displaced from hospitals will move to work in the other
      workplaces, especially the community sector. METHOD: Employment patterns were
      tracked by examining a longitudinal database of all 201,463 nurses registered
      with the College of Nurses Ontario (Canada) between 1993 and 2004. Focusing on
      the employment categories Active (Working in nursing), Eligible-Seeking nursing
      employment or Dropout from the nursing labour market, year-to-year transition
      matrixes were generated by sector and sub-sector of employment, nurse type, age
      group and work status. FINDINGS: For every nurse practising nursing in any non
      hospital job or in the community a year after leaving hospitals, an average of
      1.3 and four nurses, respectively, dropped out of Ontario's labour market. The
      proportion of nurses leaving hospitals transitioning to the Dropout category
      ranged from 63.3% (1994-95) to 38.6% (2001-02). The proportion dropping out of
      Ontario's market was higher for Registered Practical Nurses (compared to
      Registered Nurses), increased with age and decreased with degree of casualization
      in nurses' jobs. CONCLUSION: Downsizing hospitals without attention to the
      potentially negative impact on the nursing workforce can lead to retention
      difficulties and adversely affects the overall supply of nurses.

PMID- 19399978
TI  - Are probabilities overweighted or underweighted when rare outcomes are
      experienced (rarely)?
AB  - When making decisions involving risky outcomes on the basis of verbal
      descriptions of the outcomes and their associated probabilities, people behave as
      if they overweight small probabilities. In contrast, when the same outcomes are
      instead experienced in a series of samples, people behave as if they underweight
      small probabilities. We present two experiments showing that the existing
      explanations of the underweighting observed in decisions from experience are not
      sufficient to account for the effect. Underweighting was observed when
      participants experienced representative samples of events, so it cannot be
      attributed to undersampling of the small probabilities. In addition, earlier
      samples predicted decisions just as well as later samples did, so underweighting
      cannot be attributed to recency weighting. Finally, frequency judgments were
      accurate, so underweighting cannot be attributed to judgment error. Furthermore,
      we show that the underweighting of small probabilities is also reflected in the
      bestfitting parameter values obtained when prospect theory, the dominant model of
      risky choice, is applied to the data.

PMID- 19399979
TI  - Developmental "roots" in mature biological knowledge.
AB  - Young children tend to claim that moving artifacts and nonliving natural kinds
      are alive, but neglect to ascribe life to plants. This research tested whether
      adults exhibit similar confusions when verifying life status in a speeded
      classification task. Experiment 1 showed that undergraduates encounter greater
      difficulty (reduced accuracy and increased response times) in determining life
      status for plants, relative to animals, and for natural and moving nonliving
      things, relative to artifacts and non-moving things. Experiment 2 replicated
      these effects in university biology professors. The professors showed a
      significantly reduced effect size for living things, as compared with the
      students, but still showed greater difficulty for plants than animals, even as no
      differences from the students were apparent in their responses to nonliving
      things. These results suggest that mature biological knowledge relies on a
      developmental foundation that is not radically overwritten or erased with the
      profound conceptual changes that accompany mastery of the domain.

PMID- 19399980
TI  - Daily interruption of sedative infusions in an adult medical-surgical  intensive
      care unit: randomized controlled trial.
AB  - AIM: This article is a report of a study conducted to determine if a nursing
      implemented protocol of daily interruption of sedative infusions vs. sedation as
      directed by the intensive care unit team would decrease duration of mechanical
      ventilation. BACKGROUND: Continuous rather than intermittent infusion of sedative
      and analgesic agents leads to greater stability in sedation level, but has been
      correlated with prolongation of mechanical ventilation and hospitalization of
      critical care patients. Daily interruption of sedative infusions in mechanically
      ventilated patients has reduced the duration of mechanical ventilation and length
      of stay in intensive care. METHOD: A randomized controlled trial was carried out
      from November 2004 to March 2006 with 97 patients receiving mechanical
      ventilation and continuous infusion of sedative drugs in an intensive care unit
      in Greece. The primary outcome measure was the duration of mechanical
      ventilation. Secondary outcomes were length of intensive care unit stay, length
      of hospital stay, overall mortality, total doses of sedative and analgesic
      medicines and Ramsay scores and duration of cessation of sedative infusions per
      day. RESULTS: The median duration of mechanical ventilation was 8.7 days vs. 7.7
      days (P = 0.7). Length of intensive care unit stay (median: 14 vs. 12, P = 0.5)
      and in the hospital (median: 31 vs. 21, P = 0.1) was similar between the
      intervention and control groups. The absence of statistically significant
      differences in these variables remained when patients with brain injury were
      examined separately. CONCLUSION: The nursing-implemented protocol of daily
      interruption of sedative infusions was neither beneficial nor harmful compared
      with usual practice, which has as its primary target the earliest possible
      awakening of patients.

PMID- 19399981
TI  - Gaze-triggered orienting as a tool of the belongingness self-regulation system.
AB  - Social-psychological theories of belongingness self-regulation suggest that when
      one's need for interpersonal relationships is not being met, one begins to
      monitor the social environment more closely. Presumably, this serves to increase
      awareness of the likelihood of social acceptance versus rejection and to inform
      later social decision- making processes. The current investigation tested whether
      low belongingness increases a particular form of social monitoring that has
      recently been documented in the cognitive literature: gaze-triggered orienting.
      Low belongingness was operationalized either in terms of low trait self
      esteem(Studies 1a and 1b) or in terms of the priming of rejection-related
      thoughts (Study 2). Across the studies, the normal tendency to orient attention
      in accordance with another individual's eye gaze was augmented under conditions
      of low belongingness. However, belongingness had no influence on a nonsocial form
      of orienting. The results are discussed in terms of their implications for
      theories of belongingness self-regulation and social attention.

PMID- 19399982
TI  - HIV/AIDS knowledge, attitudes, practices and perceptions of rural   nurses in
      South Africa.
AB  - AIM: This paper is a report of a study exploring HIV/AIDS-related knowledge,
      attitudes, practices and perceptions of nurses in the largely black and rural
      Limpopo Province of South Africa. BACKGROUND: Studies of HIV/AIDS knowledge,
      attitudes and practices among healthcare workers in developing countries have
      shown gaps in knowledge and fear of contagion, coupled with ambivalent attitudes
      in caring for patients with HIV/AIDS and inconsistent universal precautions
      adherence. METHOD: A cross-sectional study of a random sample of primary health
      care (PHC) (n = 71) and hospital nurses (n = 69) was carried out in 2005, using a
      questionnaire, focus groups and in-depth interviews. FINDINGS: Hospital nurses
      reported a higher frequency of care for patients with HIV/AIDS (P < 0.05), but
      less HIV/AIDS training when compared to PHC nurses (P < 0.001). HIV/AIDS
      knowledge was moderately adequate and associated with professional rank,
      frequency of care and training (P < 0.001). Attitudes towards patients with
      HIV/AIDS were mainly positive and were statistically significantly correlated
      with HIV/AIDS knowledge (P < 0.01) and training (P < 0.05). Three out of four
      nurses reported that they practised universal precautions (76.1%), but fear of
      occupational HIV transmission and lack of injection safety was found. Seven in 10
      nurses reported previous needlestick injuries, but postexposure prophylaxis was
      not available in all healthcare facilities. Participants reported a higher
      workload because of HIV/AIDS, lack of training impacting negatively on their
      work, and stigma and shared confidentiality affecting them emotionally.
      CONCLUSION: There is a need for accelerated HIV/AIDS training of rural nurses and
      for wider implementation of universal precautions and postexposure prophylaxis
      availability in public health facilities in southern Africa.

PMID- 19399983
TI  - Clinical, salivary, and bacterial markers for caries risk  assessment in
      schoolchildren: a 4-year follow-up.
AB  - BACKGROUND: In Mexico, there is a high prevalence of dental caries and large
      groups of children still show extensive untreated dental damage. AIM: This study
      aims to evaluate, in a cohort of 6-year-old Mexican children, the relationship
      between caries increment at 4 years and the following caries risk markers:
      fissure morphology, caries experience, salivary flow rate, Snyder test results,
      and mutans and lactobacilli counts. DESIGN: To predict new caries lesions in 110
      schoolchildren, clinical, salivary, and bacteriological caries risk markers were
      used, including fissure morphology, caries experience, salivary flow rate, Snyder
      test, and Streptococcus mutans and lactobacilli counts. To determine the validity
      of these markers, the baseline data were compared with the caries increment after
      4 years. RESULTS: The risk model's capacity to predict caries was moderate
      (specificity 79.6% and sensitivity 78.6%). Caries experience (P = 0.0001), Snyder
      test (P = 0.002), and fissure morphology (P = 0.024) had the strongest
      association with caries increment. Salivary flow rate, lactobacilli, and S.
      mutans counts did not contribute significantly to the prediction of caries
      lesions in these children. CONCLUSION: In addition to the initial caries
      experience, tooth morphology and Snyder test proved to be useful predictors for
      caries. These three risk markers may be particularly useful in targeting caries
      prevention efforts in developing countries.

PMID- 19399984
TI  - Telenurses' experiences of working with computerized decision support:
      supporting, inhibiting and quality improving.
AB  - AIM: This paper is a report of a study conducted to describe telenurses'
      experiences of working with computerized decision support systems and how such
      systems could influence their work. BACKGROUND: Telenursing is an expanding
      service in many Western countries, and in recent years centralization of
      telenursing services has occurred in Sweden. In connection with this, the use of
      computerized decision support has increased. METHOD: Eight Registered Nurses from
      three telephone advice call centres in Sweden who were using computerized
      decision support took part in semi-structured interviews in 2006. The data were
      analysed using qualitative content analysis. FINDINGS: The findings are presented
      as one theme and three categories. Telenurses experienced their work with a
      decision support system as supporting, inhibiting and quality improving. Based on
      two of the categories - 'supporting' and 'inhibiting' - a theme was revealed:
      being strengthened, but simultaneously controlled and inhibited. This theme
      represents the individual level. The telenurses found that the decision support
      system simplified their work, complemented their knowledge, gave them security
      and enhanced their credibility. They also described experiencing the system as
      incomplete, sometimes in conflict with their own opinions and controlling. The
      third category referred to the organizational level: the decision support system
      ensured the quality of telenursing. CONCLUSIONS: Although the telenurses
      experienced computerized decision support as both supporting and inhibiting, they
      preferred working with it. They also described how a computerized decision
      support system cannot replace telenurses' knowledge and competence, and that it
      should be considered as complementary.

PMID- 19399985
TI  - Index of sources of stress in nursing students: a confirmatory factor  analysis.
AB  - AIM: This paper is a report of a study to test the proposed factor structure of
      the Index of Sources of Stress in Nursing Students. BACKGROUND: Research across
      many countries has identified a number of sources of distress in nursing students
      but little attempt has been made to understand and measure sources of eustress or
      those stressors likely to enhance performance and well-being. The Index of
      Sources of Stress in Nursing Students was developed to do this. Exploratory
      factor analysis suggested a three-factor structure, the factors being labelled:
      learning and teaching; placement-related and course organization. It is
      important, however, to subject the instrument to confirmatory factor analysis as
      a further test of construct validity. METHOD: A convenience sample of final year
      nursing students (n = 176) was surveyed in one university in Northern Ireland in
      2007. The Index of Sources of Stress in Nursing Students, which measures sources
      of stress likely to contribute to distress and eustress, was completed
      electronically. The LISREL programme was used to carry out the confirmatory
      factor analysis and test the factor structure suggested in the exploratory
      analysis. FINDINGS: The proposed factor structure for the items measuring
      'Uplifts' proved to be a good fit to the data and the proposed factor structure
      for the items measuring 'Hassles' showed adequate fit. CONCLUSION: In nursing
      programmes adopting the academic model and combining university-based learning
      with placement experience, this instrument can be used to help identify the
      sources of stress or course demands that students rate as distressing and those
      that help them to achieve. The validity of the ISSN could be further evaluated in
      other education settings.

PMID- 19399986
TI  - Brain gain: the underground world of neuroenhancing drugs.

PMID- 19399987
TI  - Aquatic Animal Models of Human Disease. Proceedings of the 4th Conference,
      Durham, NC, USA, January 31-February 3, 2008.

PMID- 19399988
TI  - Proceedings of the 4th International Conference on Analysis of Microbial Cells at
      the Single Cell Level, Bad Schandau, Germany, 22-25 May 2008.

PMID- 19399990
TI  - Co-evolution of new immunotherapeutics and   anti-infective strategies.

PMID- 19399989
TI  - Hedgehog signalling: emerging evidence for non-canonical pathways.
AB  - Hedgehog (HH) signalling is involved in the development of numerous embryonic
      tissues. In humans,germline mutations in hedgehog pathway components cause
      congenital malformations and somatic mutations are associated with cancers. The
      basic framework of the HH pathway was elucidated in the fruitfly, Drosophila
      melanogaster, and this pathway is largely conserved in vertebrates, although some
      important differences have been noted. The current paradigm of the "canonical"
      pathway views HH signalling as a series of repressive interactions which
      culminates in GLI-mediated transcriptional regulation of a variety of cellular
      processes. Definitions of "non-canonical" signalling stem from examples where the
      response to HH morphogen deviates from this paradigm and, according to current
      reports, three general scenarios of noncanonical HH signalling can be defined:
      (1) Signalling that involves HH pathway components but which is independent of
      GLI-mediated transcription; (2) Direct interaction of HH signalling components
      with components of other molecular pathways; and (3) "Non-contiguous" or
      "atypical" interaction of core HH pathway components with one another. Currently,
      the evidence supporting non-canonical HH signalling is not conclusive. However,
      Sonic hedgehog (SHH) has been shown to regulate cell migration and axon guidance
      in several contexts, and some of these processes are independent of downstream
      components of the HH pathway, and presumably the transcriptional response to
      morphogen. Furthermore, biochemical studies have shown that the HH receptor,
      PTCH1, can directly interact both with Cyclin B1 and caspases, to inhibit cell
      proliferation and to promote apoptosis, respectively, and that these functions
      are inhibited in the presence of morphogen. Genetic analysis of orthologues of
      the HH pathway in nematode worms further supports the notion that PTCH1-related
      molecules can function independently of other components of the canonical HH
      pathway, and the phenotypes of mice with point mutations in the Ptch1 gene offer
      clues as to the processes that non-canonical HH signalling might regulate. While
      none of these evidences are conclusive,collectively they point to the existence
      of added complexity in the HH pathway in the form of non-canonical pathways. A
      major difficulty in studying this problem is that canonical and non-canonical
      pathways are likely to act in parallel, and so in many situations it will not be
      possible to implicate non-canonical responses in certain cellular processes
      simply by excluding a role for the canonical pathway-directed analyses of non
      canonical HH signalling are therefore necessary. The aim of this review is to
      present the cumulative evidence supporting non-canonical HH signalling, with the
      hope of promoting further enquiry into this area.

PMID- 19399991
TI  - Characterization of a small erythromycin resistance plasmid pLFE1 from the food
      isolate Lactobacillus plantarum M345.
AB  - This paper reports the complete 4031 bp nucleotide sequence of the small
      erythromycin resistance plasmid pLFE1 isolated from the raw-milk cheese isolate
      Lactobacillus plantarum M345. Analysis of the sequence revealed the coding
      regions for the erythromycin resistance determinant Erm(B). A replication
      initiation protein RepB was identified belonging to the RepB proteins of the
      pMV158 family of rolling-circle replicating plasmids. The transcriptional
      repressor protein CopG and a small counter transcribed RNA, two elements
      typically involved in replication control within this family were also found. A
      putative replication initiation site including a single-strand origin (sso) -like
      region succeeded by a characteristic pMV158 family double-strand origin (dso) was
      located upstream of the replication region. An open reading frame following a
      typical origin of transfer (oriT) site and coding for a putative truncated
      mobilization (Mob) protein with a size of 83 aa was detected. The product of the
      putative mob gene showed large similarity to the N-terminal region of the pMV158
      family of Pre/Mob proteins, but was much smaller than other proteins of this
      family. We therefore suggest that the Mob function in pLFE1 is supplied in trans
      from another plasmid present in L. plantarum M345.Filter-mating experiments
      showed that pLFE1 has a broad host-range with transconjugants obtained from
      Lactobacillus rhamnosus, Lactococcus lactis, Listeria innocua, the opportunistic
      pathogen Enterococcus faecalis and the pathogen Listeria monocytogenes.

PMID- 19399992
TI  - Dealing with immunogenicity of biologicals: assessment and   clinical relevance.
AB  - PURPOSE OF REVIEW: In the last decade, biologicals revolutionized rheumatology.
      An increasing number of patients benefit from biotherapeuticals. However, some
      patients do not respond to treatment and others lose their response after a
      certain time. Immunogenicity is one of the factors linked to secondary
      nonresponse but its clinical significance has remained controversial. RECENT
      FINDINGS: In recent years, knowledge of how to assess immunogenicity of
      biologicals has improved. Various reports show an inverse relationship between
      drug levels and antibody formation against the drug. Studies associated
      immunogenicity of therapeutic antibodies with clinically significant nonresponse
      in a subgroup of patients. Clinically relevant immunogenicity is influenced by
      several factors including dosing and concomitant medication. It has been shown
      that immunogenicity against biologicals can be persistent or transient. SUMMARY:
      Immunogenicity affects a significant number of patients treated with biologicals.
      Monitoring of drug levels as well as of antibodies against therapeutic antibodies
      may lead to more rational treatment strategies.

PMID- 19399993
TI  - Improved lux reporters for use in Staphylococcus aureus.
AB  - The use of luxABCDE (lux) offers certain advantages over other reporters, such
      as: lacZ and xylE. It is real time and its signal generation is produced without
      the requirement for any additional substrates. In some bacteria such as
      Staphylococcus spp, light production by luciferase is restricted because of a
      limited availability of endogenous substrates such as fatty acid aldehyde. We
      describe the construction of promoterless-lux cloning vectors, pGYlux and
      pAmilux. S. aureus carrying B. subtilis xyl/tetO promoter fused to the lux genes
      of pGYlux gave up to a 2.5-fold enhancement of luminescence over S. aureus
      carrying the xyl/tetO promoter fused to lux genes of the previously published
      parent vector pAL2. Furthermore, pAmilux showed a 6-fold enhancement of lux
      expression when compared to pGYlux in S. aureus. This was achieved by cloning the
      constitutive ami promoter upstream of the luxCDE genes to increase endogenous
      fatty acid aldehyde production while maintaining its reporter functionality by
      fusing promoters to the luxAB genes.

PMID- 19399994
TI  - A guide and guard: the many faces of T-cadherin.
AB  - Cadherins are a superfamily of transmembrane proteins that mediate calcium
      dependent intercellular adhesion. T-cadherin (T-cad, H-cadherin or cadherin-13)
      is an atypical member, lacking transmembrane and cytosolic domains and possessing
      a glycosylphosphatidylinositol moiety that anchors T-cadherin to the plasma
      membrane. This article reviews current knowledge on the biomolecular
      characteristics of T-cadherin,its expression and function in different tissues in
      health and disease and its mechanisms of signal transduction. The structural
      characteristics of T-cadherin protein predict that it is unlikely to function as
      a"true" adhesion molecule in vivo. Studies from different fields suggest that it
      may act rather as a signalling receptor participating in recognition of the
      environment and regulation of cell motility, proliferation and phenotype.
      Cellular expression levels of T-cadherin in various tissues frequently correlate
      (be it negatively or positively) with the proliferative potential of the cells.
      Loss- and gain-of-function studies demonstrate the ability of T-cadherin to
      modulate cell motility and growth. Gathering evidence suggests that the
      "functional predestination" of T-cadherin is in control of tissue architecture
      through "guiding" navigation of moving structures, segregating functional tissue
      compartments and "guarding" integrity of functionally connected tissue layers.

PMID- 19399995
TI  - What is the value of mycophenolate mofetil as induction and  maintenance therapy
      in lupus nephritis?
AB  - PURPOSE OF REVIEW: Mycophenolate mofetil (MMF) is an alternative to
      cyclophosphamide for the treatment of lupus nephritis. The precise role of MMF is
      under ongoing evaluation. This review provides an up-to-date summary of MMF and
      its use as remission induction and maintenance therapy for lupus nephritis.
      RECENT FINDINGS: For remission induction, recent randomized trial data suggest
      that MMF is at least as good as intravenous cyclophosphamide in terms of efficacy
      and safety. MMF may have superior efficacy to intravenous cyclophosphamide in
      black populations. Preliminary data suggest that MMF with tacrolimus may have
      added benefit over cyclophosphamide. For remission maintenance, limited evidence
      suggests that MMF is superior to quarterly intravenous cyclophosphamide and
      equivalent to azathioprine. SUMMARY: MMF is likely to be noninferior to
      cyclophosphamide for the induction of remission in lupus nephritis. Early results
      suggest that MMF is equivalent to azathioprine for remission maintenance,
      although large randomized trial data are awaited to clarify the role. The optimal
      dosing strategy and duration of MMF treatment have not been established. The
      efficacy and safety of MMF in patients with severe renal impairment requires
      further investigation. Longer follow-up is required to fully assess the impact of
      MMF on renal survival and overall mortality.

PMID- 19399996
TI  - NMR quantitation of natural products at the nanomole scale.
AB  - We describe a simple and accurate method for quantitation by solvent 13C
      satellites (QSCS) of very small amounts of natural products using microprobe NMR
      spectroscopy. The method takes advantage of integration of 13C satellite peaks of
      deuterated solvents, in particular CDCl3, that have favorable intensities for
      measurements of samples in NMR microcoils and microprobe tubes in the 1-200
      nanomole range.

PMID- 19399997
TI  - Italy urged to give end-of-life bill more time for debate.

PMID- 19399998
TI  - Novartis under fire for accepting new reward for old drug.

PMID- 19399999
TI  - Outlook hazy for smoking rates in the USA.

PMID- 19400000
TI  - North Korea halts foreign food-aid programme.

PMID- 19400001
TI  - Human papillomavirus, abstinence, and the other risks.

PMID- 19400002
TI  - Do fast food restaurants contribute to obesity?

PMID- 19400003
TI  - The role of patient amenities in hospital demand.

PMID- 19400004
TI  - More on school nurse workloads.

PMID- 19400005
TI  - "Habitomegaly"? Fat chance!

PMID- 19400006
TI  - Seeing is believing.

PMID- 19400007
TI  - Need feedback on labor encouragement method.

PMID- 19400008
TI  - Are overweight adolescents at higher risk of engaging in unhealthy weight-control
      behaviours?
AB  - AIM: To examine correlates of unhealthy weight-control behaviours (UNWCB), and to
      explore possible associated variables. METHODS: Sample included 3762, 8th and
      10th grade public school Portuguese students who participated in the 2002 Health
      Behaviour in School-Aged Children (HBSC)/World Health Organization (WHO) survey
      of adolescent health. Factor analysis was used, and two scales were identified as
      'healthy weight-control behaviours' (HWCB) and 'UNWCB' through Kaiser criteria
      analysis. Frequency scores were developed and used in analysis of variance
      (ANOVAs) test as dependent variables, according to gender and age. Pearson
      correlations and post-hoc analysis were performed to identify potential
      associations. RESULTS: UNWCB were significantly higher among those who were
      dieting or not dieting, but considering they should, and were significantly and
      progressively increasing from those perceiving themselves as thin, to those
      perceiving themselves as being the right size and those perceiving themselves as
      fat. Overweight reported more frequently than non-overweight, both HWCB and
      UNWCB. Finally, there were significant differences concerning alcohol use, with
      UNWCB increasing progressively from reporting 'drinking rarely or never' to
      'drinking every week' and 'everyday'. CONCLUSION: Because UNWCB are associated
      with both medical and psychological health risks, routine screening is warranted.
      Special attention needs to be directed towards youth at greatest risk for
      disordered eating, including overweight youth.

PMID- 19400009
TI  - Health tips.  Luggage without pain.

PMID- 19400010
TI  - Pneumococcal vaccine may reduce heart attack risk.

PMID- 19400012
TI  - Knee ligament surgery.  Age limits are changing.

PMID- 19400011
TI  - Small intestinal bacterial overgrowth.  Cause of digestive trouble.

PMID- 19400013
TI  - I'm an 82-year-old man, and in the last couple of years I seem to have lost all
      the muscle in my thighs and upper arms.  I walk a lot for my part-time job and at
      home.  None of this seems to help.  Is this just the result of getting older?

PMID- 19400014
TI  - Buruli ulcer: dare we continue to ignore it?

PMID- 19400015
TI  - Mobile phones connecting efforts to tackle infectious disease.

PMID- 19400016
TI  - Assignment of female convicts on the Hunter River, 1831-1840.
AB  - Assignment has been viewed as an instrument of oppression and exploitation of
      female convicts. This local study examines a group of female convicts assigned on
      the Hunter River from the Newcastle Female Factory over a ten-year period. It
      reveals one aspect of the diverse story that was the female convict experience.
      The strategies employed by some of these women demonstrates that they had a
      degree of autonomy not usually conceded.

PMID- 19400017
TI  - "How are the Egyptians behaving?" Herbert Brookes, British-Australian.
AB  - Herbert Brookes was a wealthy businessman, a distinguished patron of high culture
      in Melbourne society, an anti-Labor eminence who moved comfortably in the highest
      of imperial circles. The richness of his papers in the National Library provides
      the opportunity to examine the life of a leading British-Australian, to analyse
      issues of conscience and purpose that do not figure much in current
      historiography and perhaps to throw new light on the concerns of the generation
      that saw its world disrupted after 1914. Using the notion of Protestant
      stewardship, I have suggested that Brookes' life offers one way into the dynamics
      of liberalism before the Great War and of loyalism after it.

PMID- 19400018
TI  - The master potter and the rejected pots: eugenic legislation in Victoria, 1918
      1939.
AB  - In the period since Carol Bacchi introduced eugenics into Australian
      historiography in 1980, much has been written that has increased our
      understanding of the role eugenics played in the development of Australian
      society in the first half of this century. It is now generally recognised that
      eugenics developed after the first world war from a relatively simplistic
      scientific justification of racist and class-biased social Darwinism into a
      movement concerned with using environmental reforms to help a wide range of
      Australians reach their full potential. In the interwar years the reform
      eugenicists (as they have been named) were active in a wide range of
      environmental movements including health reforms, slum clearance and educational
      improvements. The corollary of reform eugenics was based on the belief that
      heredity was an impassable obstacle for some: mental deficients were not
      considered to be racially 'fit' or 'efficient' enough to benefit from the
      reforms. Whilst this side of reform eugenics is well known in other countries
      (sterilisation programmes in Germany, the United States and Scandinavia being
      examples), it is yet to receive much attention so far in the discussion about
      Australia in the interwar years. This article argues that the attempt of a group
      of influential reform eugenicists in Victoria in the interwar years to institute
      legislation aimed at denying a significant proportion of the population the most
      basic rights of citizenship (including the right to reproduce) redresses the
      imbalance in our understanding of reform eugenics in the interwar years.

PMID- 19400019
TI  - Windows on other worlds: the rise and fall of sideshow alley.
AB  - This article explores the world of Sideshow Alley, which emerged from the ancient
      fair culture of Britain and took root in the agricultural show movement of
      Australia by the 1880s. There it flourished until the 1950s, when modernity and
      respectability caused its demise. The article also argues that Sideshow Alley was
      a place of power that helped to shape the identities of many Australians through
      the display of difference and that it also provided a site of agency for those
      displaying themselves.

PMID- 19400020
TI  - Australian surf life-saving and the "forgotten members".
AB  - The history and mythology of Australia's surf life-saving movement portray the
      surf life-saver as an inter and postwar national symbol, an image of manhood
      often regarded as the successor to that of the bushman and the digger. According
      to this viewpoint, women had no place on the beaches, being supportive
      fundraisers and social organisers. In fact, almost from surf life-saving's
      commencement in 1906, many women refused to be confined to these roles; they
      participated in their own competitions, were proficient in rescue techniques and
      were proud to belong to the movement, thus contradicting the widely shared belief
      that their active involvement began only in 1980 when they were granted full
      membership.

PMID- 19400021
TI  - Preserving Sydney's built heritage in the early twentieth century.
AB  - Modernity has been antithetical to heritage conservation in the twentieth
      century. The value of inherited buildings was not widely acknowledged by
      government officials, politicians, architects, planners and the broader community
      until the' 1970s. From the turn of the century, a coalition of pioneering
      preservationists in Sydney confronted a formidable growth mentality, which linked
      preservation with economic and cultural stasis. This article explores the
      objectives, composition, ideology, modus operandi and record of the fledgeling
      preservation movement against the backdrop of modernisation.

PMID- 19400023
TI  - Pain and dorsiflexion range of motion predict short- and medium-term activity
      limitation in people receiving physiotherapy intervention after ankle fracture:
      an observational study.
AB  - QUESTION: What predicts short - and medium term activity limitation in people
      after ankle fracture? DESIGN: Inception cohort observational study. PARTICIPANT:
      Adults with ankle fracture recruited within days following cast removal from
      physiotherapy departments of teaching hospital in Sydney, Australia. OUTCOME
      MEASURES: The predictive value of variables that were injury-related (fracture
      management, fracture severity, angle of the ankle during cast immobilisation, and
      time from cast removal to baseline) and performance-related (activity limitation,
      pain, mobility and dorsiflexion range of motion measured soon after cast removal)
      were examined in one dataset (n = 150) using univariate linear regression.
      Significant variables (p <or = 0.20) were further examined with a multivariate
      linear model. A clinical prediction rule was derived then validated using data
      from an independent dataset (n = 94). RESULTS: Fracture management, fracture
      severity, baseline activity limitation, pain, mobility and dorsiflexion had
      significant but weak univariate associations with activity limitation. Only pain
      and dorsiflexion range of motion contributed independently to the clinical
      prediction rule. When applied to the validation data, the rule explained 12% of
      the short-term and 9% of the medium-term variance in activity limitation.
      CONCLUSION: Performance-related variables were stronger predictors than injury
      related variables. A clinical prediction rule consisting of pain and dorsiflexion
      range of motion explained a small amount of variance in short- and medium-term
      activity limitation, suggesting that it may be appropriate to identify people
      with high levels of pain and restricted dorsiflexion after ankle fracture and
      target intervention accordingly.

PMID- 19400022
TI  - From solitary vice to split mind: psychiatric discourses of male sexuality and
      coming of age, 1918-1938.
AB  - Early in this century, adolescence began to emerge as a discrete, biologically
      based and, therefore, "natural" subject category. The psychiatric profession
      engaged in the discursive production of the adolescent through the
      identification, classification and use of the psychiatric illness of adolescent
      insanity. The mental disease of youth, dementia praecox, drew young men into a
      tutelary relationship with psychiatrists, who were eager to delineate the
      appropriate strategies for avoidance of the age-specific mental disease.

PMID- 19400024
TI  - Changes to recognize--oncology billing and administration.

PMID- 19400025
TI  - Statement on dengue.  An Advisory Committee Statement (ACS).

PMID- 19400026
TI  - An update on the invasive meningococcal disease and meningococcal vaccine
      conjugate recommendations. An Advisory Committee Statement (ACS).

PMID- 19400027
TI  - Case of the month. Foreign body granuloma.

PMID- 19400028
TI  - Bibliography. Current world literature. Pathogenesis and immune response.

PMID- 19400029
TI  - Interaction of beef-heart mitochondrial ATPase, coupling factor F1, with
      aurovertin.
AB  - The antibiotic aurovertin binds to beef-heart mitochondrial ATPase, coupling
      Factor F1, with biphasic fluorescence enhancement. Specific binding effects,
      polarity and viscosity changes may all contribute to the enhancement. Evidence is
      presented that it stems from aurovertin binding followed by a slow conformational
      change in F1. This occurs more rapidly in dissociated F1. The effect of
      substrates of the enzyme on the fluorescence enhancement is examined. Evidence is
      presented that in the absence of added magnesium, F1 can hydrolyse low
      concentrations of added ATP.

PMID- 19400030
TI  - Effects of quercetin and F1 inhibitor on mitochondrial ATPase and energy-linked
      reactions in submitochondrial particles.
AB  - Quercetin (3,3',4',5,7-pentahydroxyflavone) shares certain properties with the
      mitochondrial ATPase inhibitor protein. At low concentrations it inhibits both
      soluble and particulate mitochondrial ATPase and has no effect on oxidative
      phosphorylation in submitochondrial particles. Unlike the mitochondrial inhibitor
      protein quercetin inhibits the ATP-dependent reduction of NAD+ by succinate in
      fully reconstituted submitochondrial particles. A comparison of various flavones
      indicates that the hydroxyl groups at the 3' and perhaps 3 position are important
      for the inhibition of ATPase activity.

PMID- 19400031
TI  - Spegazzinine, a new inhibitor of mitochondrial oxidative phosphorylation.
AB  - The effects of spegazzinine, a dihydroindole alkaloid, on mitochondrial oxidative
      phosphorylation were studied. Spegazzinine inhibited coupled respiration and
      phosphorylation in rat liver mitochondria. The I50 was 120 microM. Uncouplers
      released the inhibition of coupled respiration. Arsenate-stimulated mitochondrial
      respiration was partially inhibited by spegazzinine. The stimulation of
      mitochondrial respiration by Ca2+ and the proton ejection associated with the ATP
      dependent Ca2+ uptake were not affected by the alkaloid. Oxidative
      phosphorylation and the Pi-ATP exchange reaction of phosphorylating beef heart
      submitochondrial particles were strongly inhibited by spegazzinine (I50, 50
      microM) while the ATP-dependent reactions, reduction of NAD+ by succinate and the
      pyridine nucleotides transhydrogenase were less sensitive (I50, 125 microM).
      Oxygen uptake by submitochondrial particles was not affected. The 2,4
      dinitrophenol-stimulated ATPase activity of rat liver mitochondria was not
      affected by 300 microM spegazzinine, a concentration of alkaloid that completely
      inhibited phosphorylation. However, higher concentrations of spegazzinine did
      partially inhibit it. The ATPase activities of submitochondrial particles,
      insoluble and soluble ATPases were also partially inhibited by high
      concentrations of spegazzinine. The inhibitory properties of spegazzinine on
      energy transfer reactions are compared with those of oligomycin, aurovertin and
      dicyclohexylcarbodiimide. It is concluded that spegazzinine effects are very
      similar to the effects of aurovertin and that its site of action may be the same
      or near the site of aurovertin.

PMID- 19400032
TI  - Mechanism of inhibition of the dicarboxylate carrier of mitochondria by thiol
      reagents.
AB  - The nature of the inhibition of the dicarboxylate carrier by compounds reacting
      with SH groups has been investigated. (1) Mersalyl and p-hydroxymercuribenzoate
      increase the Km without changing the V of malonate/Pi exchange, when they are
      added simultaneously with the dicarboxylate. If, on the other hand, the
      mitochondria are preincubated with SH reagents prior to the addition of malonate,
      the mersalyl inhibition of malonate/Pi exchange becomes predominantly non
      competitive with respect to malonate. (2) In the case of Pi/Pi exchange,
      catalyzed by the dicarboxylate carrier, the mersalyl inhibition is competitive
      with respect to Pi (as indicated by Lineweaver-Burk plots), even when mersalyl is
      added before the substrate. Dixon plots of the rate of Pi uptake against mersalyl
      concentration are, however, non-linear, suggesting that the inhibition is
      partially competitive. (3) Dicarboxylates and dicarboxylate analogous protect
      against SH reagent inhibition of both dicarboxylate and Pi uptake via the
      dicarboxylate carrier. The protectors are effective when added before, or
      together with the SH reagents, but do not reverse the inhibition once it has been
      established. Protection by substrate analogues progressively decreases, as the
      time of incubation with the SH reagent increases. (4) The presence of Pi does not
      protect against the SH reagent inhibition of the Pi uptake. (5) The rate of SH
      reagent inhibition of the dicarboxylate carrier is competively inhibited by
      dicarboxylates. (6) It is concluded that SH reagents bind at or near the
      dicarboxylate specific binding site and distant from the Pi binding site. As a
      result of this reaction these inhibitors prevent dicarboxylate binding directly
      and decrease the affinity for Pi by an indirect conformational change.

PMID- 19400033
TI  - Biochemical and biophysical studies on cytochrome c oxidase. XIII. Effect of
      cholate on the enzymic activity.
AB  - (1) Cholate is a mixed-type inhibitor of the enzymic activity of cytochrome c
      oxidase. The rate equations for mixed-type inhibition of the enzyme have been
      derived, based on Minnaert's Mechanism IV (1961, Biochim. Biophys. Acta 50, 23
      34). The Ki of cholate for the free enzyme (E) and for the complexes of the
      enzyme with cytochrome c (ES and EP) was determined, being 125 and 190 microM,
      respectively. (2) Comparison of the properties of cholate and the intrinsic
      inhibitor of cytochrome c oxidase (Van Buuren et al. (1971) Biochim. Biophys.
      Acta 243, 468-480) with respect to their type of inhibition and their affinity
      for enzyme, reveals that they are identical.

PMID- 19400034
TI  - The respiratory chain of Azotobacter vinelandii. III. The effect of cyanide in
      the presence of substrates.
AB  - (1) Cyanide (100 microM) causes a rapid disappearance of the band (648 nm) of
      oxidized cytochrome d in particles of Azotobacter vinelandii oxidizing NADH. The
      rate of disappearance of the band can be related to the rate of inhibition of the
      oxygen consumption. (2) The kinetics of the disappearance of the 648-nm band of
      cytochrome d with excess cyanide in the presence of substrates deviate from first
      order, indicating that at least two conformations of the enzyme are involved. (3)
      The rate of binding of cyanide to cytohrrome d increases the larger the rate of
      turnover of the oxidase. From this it is concluded that cyanide binds
      preferentially to the enzymically active oxidized conformation of cytochrome d.
      (4) The instantaneous inhibition of the oxidation of ascorbate plus N,N,N',N'
      tetramethyl-p-phenylenediamine (TMPD) by cyanide is related neither to the
      binding of cyanide to cytochrome d as determined spectrophotometrically, nor to
      the rate of inhibition of the oxidation of NADH. This indicates that different
      oxidases are involved in the oxidation of NADH and of ascorbate plus N,N,N',N'
      tetramethyl-p-phenylenediamine (TMPD), in line with the conclusion of Jones and
      Redfearn (1967) Biochim. Biophys. Acta 143, 340-353. (5) From experiments in
      which the change in redox states of cytochrome b1 and c-551 were related to the
      rate of binding of cyanide to cytochrome d, it is concluded that the cytochromes
      b1 and d are located in the main pathway to oxygen, whereas cytochrome c-551
      functions in the branch via cytochrome o. (6) After prolonged incubation of
      particles with cyanide in the presence of NADH a residual activity (5%) was found
      in which a b-type cytochrome is involved. This shows the existence of a third but
      minor pathway to oxygen.

PMID- 19400035
TI  - The respiratory system of the marine bacterium Beneckea natriegens. I. Cytochrome
      composition.
AB  - (1) The cytochrome composition of Beneckea natriegens grown under aerobic
      conditions has been examined. (2) Cell-free extracts obtained by sonication were
      separated into particulate and supernatant fractions by centrifugation at 150,000
      x g. (3) The particulate fraction contained cytochromes b562, b557, b or c554,
      c549.5, c547, and low concentrations of cytochromes a1 and a2. (Subscripts refer
      to the wavelength optima of the b and c type cytochrome alpha-peaks in low
      temperature (77 degrees K) difference spectra.) Also present was a second
      cytochrome c549.5 which is capable of binding carbon monoxide (cytochrome
      c549.5(CO)) and which is also found in the supernatant fraction. (4) Reduced plus
      CO minus reduced difference spectra had spectral peaks corresponding to
      cytochrome o and two c type cytochromes, and low concentrations of cytochromes a1
      and a2. (5) Action spectra for the relief of CO inhibition showed that cytochrome
      a2, the CO binding c type cytochrome(s) and possibly cytochrome o, but not
      cytochrome a1, had oxidase activity in intact cells. In cells grown to the late
      stationary phase, when cytochrome a2 and particularly cytochrome a1 were induced,
      the primary functual oxidase was cytochrome a1.

PMID- 19400036
TI  - Comparative studies on nicotinamide nucleotide transhydrogenase from different
      sources.
AB  - (1) Nicotinamide nucleotide transhydrogenases in submitochondrial particles from
      beef heart mitochondria, chromatophores from Rhodospirillum rubrum and membrane
      preparations from Escherichia coli and Pseudomonas aeruginosa have been compared
      with respect to the following properties: stereospecificity for the 4-hydrogen of
      NADH, reactivity with 3'-NADP, inhibition by palmityl-CoA, sensitivity tot
      rypsin, and effects of Ca2+ and 2'-AMP on the reaction rates. (2)
      Transhydrogenases from submitochondrial particles, R. rubrum chromatophores and
      E. coli membrane preparations have A-side stereospecificity for NADH, do not
      react with 3'-NADP, are inhibited by palmityl-CoA and are extremely sensitive to
      trypsin treatment. No effects of Ca2+ or 2'-AMP on the reaction rates were
      observed. In R. rubrum chromatophores trypsin-sensitive sites are present both in
      the soluble transhydrogenase factor and in the membrane preparation devoid of
      transhydrogenase factor. (3) In contrast, P. aeruginosa transhydrogenase is
      allosterically regulated by Ca2+ and 2'-AMP, is reactive with 3'-NADP, has B-side
      stereospecificity for NADH and is insensitive to palmityl-CoA or trypsin
      treatment. (4) It is concluded that the properties characterizing the
      transhydrogenase in E. coli, R. rubrum chromatophores and submitochondrial
      particles are closely connected with the interaction of the enzyme with an energy
      conserving membrane system.

PMID- 19400037
TI  - The absolute quantum efficiency of bacteriochlorophyll photooxidation in reaction
      centres of Rhodopseudomonas spheroides.
AB  - The widely assumed correspondence between fluorescence and photochemistry in
      photosynthetic systems has recently been challenged by observations on the
      triplet state of bacteriochlorophyll in reaction centres of Rhodopseudomonas
      spheroides. In order to check this assumption we have conducted a precise
      determination of the quantum efficiency of bacteriochlorophyll photooxidation in
      reaction centres at room temperature. We find a quantum efficiency of 1.02 +/-
      0.04 in contrast to a value of about 0.7 predicted from the variations in
      fluorescence yield.

PMID- 19400038
TI  - Characterization of primary reactants in bacterial photosynthesis. II. Kinetic
      studies of the light-induced EPR signal (g = 2.0026) and the optical absorbance
      changes at cryogenic temperatures.
AB  - We have shown that the rise and decay kinetics of the light-induced EPR signal
      are identical to the kinetics of the optical changes at 80 degrees K. This
      identity provides independent evidence that the EPR signal is due to the oxidized
      primary electron donor which is bacteriochlorophyll. The EPR and optical changes
      could be described by a model photochemical reaction scheme that takes into
      account spin-lattice relaxation. The optical decay rate was found to be
      temperature independent between 1.5 and 80 degrees K and to obey approximately
      first order kinetics. These results are consistent with the hypothesis that the
      charge recombination occurs via tunneling through a potential barrier. The decay
      constants at these temperatures were found to be the same for different bacterial
      species and strains. No differences were found between purified reaction centers
      of R. spheroides R-26 and whole cells. Reaction centers treated with sodium
      dodecylsulfate or urea were still photochemically active but showed a markedly
      different kinetic behavior. The decay constant may, therefore, serve as a probe
      to investigate the molecular environment of the primary reactants.

PMID- 19400039
TI  - EPR signals of oxidized plastocyanin in intact algae.
AB  - (1) An electron paramagnetic resonance (EPR) signal was observed at g = 2.05 in
      the low temperature spectra of intact cells of green, red and blue-green algae
      and of spinach chloroplasts. The g-value and the shape of the signal were similar
      to that of purified, soluble plastocyanin. (2) The amount of the copper protein,
      determined from the EPR signal height, was estimated to be nearly the same in all
      the studied organisms on the basis of the concentration of chlorophyll.
      Furthermore, it was found that the amount of the copper protein, determined from
      the EPR signal height in spinach chloroplasts corresponds with that of
      plastocyanin as determined chemically by Katoh, S., Suga, I., Shiratori, I. and
      Takamiya, A. (1961) Arch. Biochem. Biophys. 94, 136-141. (3) Experiments with far
      red and red illumination show that the site of the copper protein in vivo is in
      the electron transport pathway between Photosystems 1 and 2. Plastocyanin is not
      oxidized by illumination at 77 degrees K, indicating that no electron transfer
      occurs between the primary electron donor of Photosystem 1, P700, and
      plastocyanin at that temperature. Furthermore, the experiments suggest that in
      the intact cells of the studied algae, plastocyanin is not only reduced by
      Photosystem 2 but also by cyclic electron transport around Photosystem 1.

PMID- 19400040
TI  - [Quenching of chlorophyll in vivo by m-dinitrobenzene].
AB  - The quenching of fluorescence and inhibition of photochemical activities by m
      dinitrobenzene have been studied in unicellular algae and chloroplasts. The
      complementary area [formula: see text] is decreased in the same fashion as the
      maximum amplitude of the variable fluorescence delta phi(M), suggesting the
      invariance of S properly normalized by delta phi(M). A photochemical type
      inhibition for all photochemical activities (oxygen evolution, Photoreaction II
      and I) is observed in a concentration range higher than that required to quench
      delta phi(M). The ratio of the photochemical rate in limiting light to the O2
      burst elicited by a flash is constant whatever the level of inhibition. The
      pattern of oscillation of O2 burst during a sequence of flashes is also
      unmodified, the amplitude only being decreased. In order to explain these
      results, it is assumed that dinitrobenzene (DNB) has a quenching effect both on
      the center-chlorophyll and the collector-chlorophyll of the System II
      photosynthetic units; when the external quencher is only acting on the collector,
      the trapping efficiency for the center is unmodified, but, when the center is
      turned into its inactive form by the photochemical reaction, the fluorescence of
      the collector is quenched. It is shown that the rule of invariance of the
      normalized complementary area applies to this type of quenching; accordingly, the
      zero level of the System II fluorescence, within the constant part, (cf. Lavorel,
      J. et Joliot, P. (1972) Biophys. J. 12, 815-831) should lie close to the 0 level
      (dark-adapted state).

PMID- 19400041
TI  - Changes in chlorophyll fluorescence in relation to light-dependent cation
      transfer across thylakoid membranes.
AB  - Based on cation effects on chlorophyll a fluorescence and the light scattering
      behaviour of chloroplasts, a new interpretation of energy-dependent fluorescence
      quenching in intact leaves and isolated spinach chloroplasts is given. This type
      of fluorescence quenching is suggested to reflect movement of Mg2+ and other
      cations from the thylakoids to the stroma compartment. Cation efflux processes
      are associated with light-dependent proton uptake by thylakoids. Since cations
      strongly increase the fluorescence yield, their efflux leads to fluorescence
      lowering, apparently by means of structural changes of the membrane system.
      Similarly, the light-induced increase of apparent absorbance at 535 nm (caused by
      increased light scattering), which parallels fluorescence quenching, may reflect
      structural changes due to cation efflux from the thylakoids. In the dark these
      processes are reversed. The following results support this view: (1) After the
      envelopes of intact chloroplasts had been ruptured by osmotic shock in a medium
      of low cation content, the fluorescence yield was drastically lowered, and the
      long-term fluorescence quenching, as well as the light-dependent absorbance
      increase were missing. This is understood as being caused by loss of cations,
      which had been retained within the envelope. (2) Addition of certain cations to
      these thylakoid preparations largely restored the fluorescence signal
      characteristic of intact chloroplasts. (3) A dark period of 2-3 min in the
      presence of cations was required to produce the maximum fluorescence response.
      (4) When chloroplasts were ruptured in the presence of 5 mM MgCl2, both the
      signals of fluorescence and apparent absorbance at 535 nm remained very similar
      to those of the intact chloroplasts. (5) The described cation-dependent phenomena
      are sensitive to FCCP and closely correlated with light-induced proton uptake
      into the thylakoids, thus showing a relation to the energy conserving mechanism
      of photosynthesis.

PMID- 19400042
TI  - Restoration by sllicotungstic acid of DCMU-inhibited photoreactions in spinach
      chloroplasts.
AB  - The restoration by silicotungstic acid of the reversible light-induced pH rise
      mediated by pyocyanine in EDTA-treated chloroplasts corresponds to an
      irreversible fixation of the acid. The proton uptake is linearly related to the
      amount of fixed acid (4 protons per molecule of acid) as long as the amount of
      silicotungstic acid does not exceed 200 nmoles/mg of chlorophyll. In the same
      conditions silicotungstic acid partly restores ferricyanide reduction and O2
      evolution in chloroplasts suspensions supplemented with DCMU. These
      photoreactions are observed only with chloroplasts and these chloroplasts must
      have an unimpaired water-splitting mechanism. Silicotungstic acid does not impair
      DCMU fixation on the specific sites. More likely in its presence the properties
      of the membrane change and ferricyanide can accept electrons from a part of the
      electron transport chain, between the Photosystem II reaction center and the
      block of the electron flow by DCMU.

PMID- 19400043
TI  - New results on the properties of photosystem II centers blocked by 3-(3,4
      dichlorophenyl)-1,1-dimethylurea in their different photoactive states.
AB  - We have studied the 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) action on the
      different S states by oxygen, fluorescence and luminescence measurements. We show
      that no oxygen is evolved during a flash following the addition of DCMU to
      centers in their S3 state. This suggests that oxygen inhibition cannot be
      attributed solely to a blocking between Q and A. For all the photoinactive
      states, the only remaining pathway for the quencher reoxidation, in the presence
      of DCMU, appears to proceed through a back reaction. Therefore, the complete
      quencher regeneration still occurring when the fourth positive charge is formed
      in the presence of DCMU is also an indication of an action by DCMU at the donor
      side. The data well fit the model in which the oscillations of the fluorescence
      yield and their damping are attributed to a fast equilibrium between two forms of
      the centers: a photoactive and a photoinactive form, both of which are quenchers.
      The equilibrium constant depends on the number of positive charges stored and
      DCMU changes the characteristics of this equilibrium.

PMID- 19400044
TI  - Site-specific inhibition of photophosphorylation in isolated spinach chloroplasts
      by HgCL2. II. Evidence for three sites of energy conservation associated with non
      cyclic electron transport.
AB  - Energy transfer inhibition by HgCl2 has been demonstrated to be selective for
      certain System I partial reactions. On the basis of different HgCl2 effects on
      the System I reactions, reduced 2,6-dichlorophenolindophenol --> methylviologen,
      diaminodurene --> methylviologen and N-phenazine methosulfate cyclic, two sites
      of energy conservation associated with System I are proposed. Furthermore, these
      sites are in parallel with each other, in series with the site closely associated
      with Photosystem II and are shared between non-cyclic and cyclic electron
      transport.

PMID- 19400045
TI  - Twofold effect of valinomycin on isolated spinach chloroplasts: uncoupling and
      inhibition of electron transport.
AB  - (1) Treatment of isolated chloroplasts with valinomycin above 10(-7) M inhibits
      both photophosphorylation and ms-delayed light emission, with maximum inhibition
      occurring at 10(-5) M. (2) In the same concentration range it stimulates electron
      flow, when the pH of the medium is between 7 and 8, inhibits the extent of the
      light-induced pH change and reverses 2,3,5,6-tetramethyl-p-phenylenediamine
      quenched chlorophyll a fluorescence in the presence of 3-(3,4-dichlorophenyl)-1,1
      dimethyl urea. (3) These effects of valinomycin occur in the absence of added K+
      although the presence of K+ does facilitate its action. (4) It is suggested that
      high concentrations of valinomycin not only induce a change in the K+
      permeability but also in the H+ permeability of the thylakoid membrane and in so
      doing dissipate the high-energy state, i.e. uncouple. (5) However, electron
      transport data do not clearly demonstrate the uncoupling action of valinomycin
      since it also inhibits electron flow. (6) Valinomycin at concentrations above 10(
      6) M inhibits electron flow and stimulates chlorophyll a fluorescence of
      chloroplasts uncoupled by nigericin or NH4Cl. (7) The dual effect of valinomycin
      accounts both for the previous suggestion that this compound inhibits
      photophosphorylation by acting as an energy transfer inhibitor and also explains
      why valinomycin modifies both normal ms-delayed light and KCl-induced ms-delayed
      light transients.

PMID- 19400046
TI  - Photosynthetic regulation by cations in spinach chloroplasts.
AB  - (1) In the presence of > or =3 mM divalent cations or > or =100 mM monovalent
      cations, weak 650-nm light, presumably containing an excess of Photosystem II
      quanta, caused substantial reduction of the electron carrier pool between the two
      photoacts. In low-salt media, most electron carriers were oxidized during red
      light. (2) In the presence of low concentrations of carbonylcyanide m
      chlorophenylhydrazone (CCCP) (0.3 microM) or antimycin A (40 microM) the pool
      remained oxidized even in the presence of adequate cation concentrations. (3) The
      non-linear dependence of the O2-evolution rate upon the concentration of active
      Photosystem II trapping centers, which implies energy transfer between
      Photosystem II units, was observed only in the presence of sufficient cation. (4)
      Enhancement of the rate of methyl viologen reduction in far-red light by red
      light was found to be a weak function of Mg2+ concentration. (5) With ferredoxin
      NADP+ as acceptor, enhancement of the rate of O2 evolution in 650-nm light by far
      red light was obtained only with added Mg2+. Furthermore, Mg2+ addition markedly
      stimulated the quantum yields of NADP+ reduction, independent of wavelength, with
      either water or ascorbate-reduced 2,6-dichlorophenolindophenol (DCIP) as the
      electron donor. A dual effect of cations in the ferredoxin-NADP+ system is
      suggested. (6) With methyl viologen or potassium ferricyanide as acceptor and
      water as donor, Mg2+ did not affect the quantum yield in 650-nm light and
      slightly increased the yield at longer wavelengths. The quantum yield of the
      ascorbate-reduced DCIP-methyl viologen (Photosystem I) reaction was slightly
      decreased in 650-nm light and unaffected at long wavelengths. Our interpretation
      is that cation concentration affects the pigment distribution between
      Photosystems I and II.

PMID- 19400047
TI  - Hexosediphosphatase from spinach chloroplasts: purification, crystallization and
      some properties.
AB  - Hexosediphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11)
      has been isolated, purified, and crystallized, from previously isolated spinach
      chloroplasts. The effects of various anions, cations, and sulfhydryl compounds
      were tested, and activation by Mg2+, glycine, HCO3-, and sulfhydryl compounds is
      described. The purified enzyme is very specific for fructose 1,6-diphosphate and
      does not attack sedoheptulose-1,7-bisphosphate. The S20 value of the enzyme was
      7.7, from which the molecular weight of the enzyme was estimated as 140,000.

PMID- 19400048
TI  - Membrane polypeptides of some higher plant chloroplasts.
AB  - Sodium dodecylsulfate-polyacrylamide gel electrophoresis of membrane polypeptides
      of the mesophyll cell chloroplasts of barley, pea, and maize show similar
      profiles, with the polypeptides falling into two major groups: those associated
      with a membrane fraction enriched in Photosystem I (called Group I polypeptides)
      and those associated with a membrane fraction enriched in Photosystem II (called
      Group II polypeptides a, b, and c). In contrast to these profiles, the
      polypeptides from the extensively unstacked membranes of chloroplasts from the
      chlorophyll-deficient mutant strains of barley and pea as well as those obtained
      from the agranal bundle sheath cell chloroplasts of maize are deficient in the
      Group II polypeptides b and c. It is proposed that these polypeptides are
      required for membrane stacking in higher plant chloroplasts. These Group II
      polypeptides b and c are not required for Photosystem II activity since both the
      barley and pea mutant chloroplasts and the maize bundle sheath chloroplasts
      possess Photosystem II activities.

PMID- 19400049
TI  - On the extent of the electrical potential across the thylakoid membrane induced
      by continuous light in Chlorella cells.
AB  - The extent of the electrical potential delta phi(SS) across the thylakoid
      membrane of Chlorella cells was estimated under steady state conditions. This has
      been achieved by comparing the absorption change which occurs after continuous
      light is switched off with a calibrated field indicating absorption change
      induced by flash light. Under saturating light conditions delta phi(SS) is in the
      order of 100 mV.

PMID- 19400051
TI  - [University and the world of work: problems of interaction].

PMID- 19400050
TI  - Rapid separation of particulate components and soluble cytoplasm of isolated rat
      liver cells.
AB  - A method is described for the rapid separation of mitochondria (plus other
      particulate components) from the soluble cytoplasm of isolated rat-liver cells.
      The cells were incubated briefly with a low concentration of digitonin. After
      rapid centrifugation, the pellet contained more than 90% of the total adenylate
      kinase and glutamate dehydrogenase activities and the supernatant at least 80% of
      the lactate dehydrogenase activity. About 60% of total adenine nucleotides in
      hepatocytes were found in the soluble cytoplasm. The ATP/ADP ratio in the
      particulate fraction 80 s after exposure to digitonin of hepatocytes metabolizing
      alanine was 2.0-2.4, and that in the soluble cytoplasm 6-19. In the presence of
      atractyloside, these values were 3.5-4.4 and 1.3-2.2, respectively.

PMID- 19400052
TI  - [Study of arterial distensibility in man. Modulating mechanisms, pathological
      conditions and effects of treatment].
AB  - The reduction of large arterial distensibility has several adverse consequences
      for the cardiovascular system. This paper reviews the evidence we have obtained
      by measuring distensibility through quantification of changes in arterial
      diameter vs blood pressure changes at large elastic and middle size muscle artery
      sites. Evidence shows that arterial distensibility is reduced in conditions such
      as hypercholesterolemia, hypertension, diabetes, and congestive heart failure. In
      some conditions (e.g. hypertension) the alterations are not uniformly distributed
      in the arteries of different structure and size whereas in others (e.g. diabetes
      and heart failure) they are widespread. In diabetes evidence is available that
      distensibility changes occur early in the course of the disease. Evidence is also
      available that in all above conditions treatment can improve arterial
      distensibility thereby reversing the initial abnormality. This is due to a
      variable combination of structural and functional factors. However, technical
      ability to determine their precise role in distensibility changes in humans is
      limited.

PMID- 19400053
TI  - [Calcium score quantification using new techniques and its prognostic role in
      various subgroups of patients].
AB  - Coronary artery disease is the first cause of mortality in industrialized
      countries notwithstanding the diagnostic and therapeutic progresses. Electron
      beam computed tomography and multislice computed tomography with calcium score
      software seem to have an important role in the early diagnosis of coronary artery
      disease. Coronary calcium is associated with a high probability of subclinical
      atherosclerosis. In particular the area of calcification has a positive
      correlation with the histologically analyzed area of the atheromatous burden
      plaque. The pathophysiological mechanism may be that the calcium adherent to the
      plaque makes unstable the plaque with possible rupture. Several studies have
      analyzed the predictive value of calcium score in various subgroups of patients
      (asymptomatic, with chest pain, with diabetes) and they have confirmed the
      presence of large calcific deposits in subjects with a high cardiovascular risk.
      The correlation of the other risk factors with calcium score is unclear and
      whether this is due to genetic predisposition requires further investigation.

PMID- 19400054
TI  - [The RUTA project (Registro UTIC Triveneto ANMCO). An e-network for the coronary
      care units for acute myocardial infarction].
AB  - In the era of evidence-based medicine, the monitoring of the adherence to the
      guidelines is fundamental, in order to verify the diagnostic and therapeutic
      processes. Informatic paperless databases allow a higher data quality, lower
      costs and timely analysis with overall advantages over the traditional surveys.
      The RUTA project (acronym of Triveneto Registry of ANMCO CCUs) was designed in
      1999, aiming at creating an informatic network among the coronary care units of a
      large Italian region, for a permanent survey of patients admitted for acute
      myocardial infarction. Information ranges from the pre-hospital phase to
      discharge, including all relevant clinical and management variables. The database
      uses DBMS Personal Oracle and Power-Builder as user interface, on Windows
      platform. Anonymous data are sent to a central server.

PMID- 19400055
TI  - [The "Valle Belbo Project" for the prevention of ischemic heart disease: study
      design and correlations between alcohol and cardiovascular risk factors].
AB  - BACKGROUND: The "Valle Belbo Project" is a primary prevention study on ischemic
      heart disease, aiming at identifying cardiovascular risk factors. Detailed data
      about the amount and kind of alcohol beverages used were assessed, too. The aims
      of the present study were to evaluate the prevalence of cardiovascular risk
      factors, and the relationships between alcohol and these factors. METHODS: The
      study enrolled 3123 subjects, aged 20-65 years. Data about consumption of
      alcoholic drinks (amount and kind of beverages), smoking habits, physical
      activity during work, clinical and drug history were collected; height, weight,
      arterial blood pressure, fasting glycemia, and total cholesterol were also
      measured. RESULTS: About 57% of the subjects consumed alcoholic drinks, mostly <
      30 g/day (84%) and red wine only (80%). Prevalence of overweight/obesity,
      hypertension, hyperglycemia, hypercholesterolemia increased with higher amounts
      of alcohol consumed. A > 30 g/day alcohol use was independently associated with
      hypertension (odds ratio-OR 1.48, p = 0.03), hyperglycemia (OR 1.62, p = 0.02)
      overweight/obesity (OR 1.64, p = 0.003), and hypercholesterolemia (OR 1.69, p =
      0.001) in a multiple logistic regression model, after multiple adjustments. A <
      30 g/day red wine use was negatively correlated with hyperglycemia (OR 0.54, p <
      0.0001) and overweight/obesity (OR 0.71, p = 0.002) with respect to consumption
      of higher or other kinds of alcoholic beverages in the same model. CONCLUSIONS:
      Differently from heavy drinkers, < 30 g/day red wine drinkers are less frequently
      affected by overweight/obesity and hyperglycemia. Follow-up of these subjects may
      determine the role of alcohol effects in the incidence of ischemic heart disease.

PMID- 19400056
TI  - [Interhospital transportation for primary angioplasty in acute myocardial
      infarction: not just a simple taxi ride!].

PMID- 19400057
TI  - [An unusual cause of cardiac arrest].
AB  - The long QT syndrome is characterized by the observed association of "torsade de
      pointes" and the prolongation of the QT interval on the electrocardiogram.
      Acquired long QT syndrome typically affects older individuals, being often
      associated with the action of some drugs. Hypokalemia is a frequent cause of QT
      lengthening on the electrocardiogram. Chronic assumption of licorice may be an
      unusual cause of hypokalemia, due to its mineralocorticoid-like action. In this
      paper we describe a case of cardiac arrest due to "torsade de pointes" resulting
      from a marked hypokalemia caused by the patient's habit of eating daily a not
      negligible quantity of licorice.

PMID- 19400058
TI  - [Electrocardiographic artifacts due to the incorrect use of filters].

PMID- 19400059
TI  - Mandibular molar root resection versus implant therapy: a retrospective
      nonrandomized study.
AB  - Success rates for both periodontal and implant therapy are often dependent on
      site and tooth type. For periodontally involved mandibular molars, the decision
      to hemisect or to extract and place an implant is often complicated. The purpose
      of the present study was to evaluate the outcomes of the aforementioned treatment
      modalities for mandibular molars in a private practice setting. A retrospective
      chart review was performed. In one group of patients (n = 32), 56 mandibular
      first or first and second molars were treated by hemisection (Group H). A second
      group (n = 28) received 36 implants in the mandible to replace periodontally
      involved first or first and second molars (Group I). All patients had been in
      maintenance for at least 4 years after treatment. The occurrence and timing of
      posttreatment complications were evaluated. Data were analyzed by parametric and
      nonparametric statistics, as indicated. The majority of hemisected teeth (68% of
      Group H) and implants (89% of Group I) remained free of complications for the
      entire observation period. Group H had a greater incidence of overall
      complications (P = .027) and nonsalvageable complications (P = .013) than Group
      I. For both groups, the percent CAL loss per year was greater for the
      teeth/implants that experienced complications than in the those that remained
      complication free (p < 0.015). Within the limitations of this study, the results
      indicated that, in periodontitis patients, hemisected mandibular molars were more
      prone to complications than implants.

PMID- 19400060
TI  - The effect of fiber dowel heights in resin composite cores on restoration
      failures of endodontically treated teeth.
AB  - In vitro and in vivo testing suggest that fiber posts may reduce the incidence of
      root fractures of endodontically treated teeth. The purpose of this in vitro
      study was to compare the effect of fiber post height in resin composite cores on
      the fracture resistance of endodontically treated teeth. Forty maxillary central
      incisors were randomly divided into 2 control groups (Groups 1 and 2) of 5 teeth
      each, and 3 experimental groups (Groups 3, 4, and 5) of 10 teeth each. The teeth
      in Group 1 had their opening restored with composite resin, the teeth in Group 2
      were restored with quartz fiber posts without resin composite cores, and the
      teeth in Groups 3, 4, and 5 were restored with quartz fiber posts of 2, 4, and 6
      mm high, respectively, in 6-mm resin composite cores. Ceramic crowns were
      fabricated for the specimens. Specimens were positioned in a mounting device and
      aligned at a 130-degree angle to the long axis of each tooth. A universal testing
      machine was used to apply constant load at a crosshead speed of 0.5 mm/min until
      failure occurred. The highest fracture load and mode of failure of each specimen
      was recorded. The highest fracture resistance force was observed in Group 2
      (290.38 +/- 48.45 N) and decreased, respectively, in Group 1 (238.98 +/-26.26 N),
      Group 5 (228.35 +/-58.79 N), Group 4 (221.43 +/-38.74 N), and Group 3 (199.05 +/
      58.00 N). According to one-way analysis of variance (ANOVA) and Duncan's test (P
      < or = .05), there was no statistically significant increase in the force from
      Group 3 to Group 5, and the force in Group 2 was significantly higher than that
      of the experimental groups. There was no statistical significance difference in
      force among the experimental groups, and the amount of residual tooth structure
      was found to be the critical factor in fracture resistance. The results suggest
      that endodontically treated teeth should be restored with the longest possible
      post height while preserving maximum tooth structure.

PMID- 19400061
TI  - A method to retrieve a displaced dental implant from the maxillary sinus.
AB  - Dental implants can be displaced into the maxillary sinus. Retrieval by
      endoscopic or Caldwell-Luc techniques have been previously reported. A modified
      Caldwell-Luc technique is presented here, where a small round lateral osseous
      window is created. A plastic surgical aspirator tip is cut and modified to fit
      tightly into the access window. The sinus is filled with saline, and the patient
      is placed in a lateral recumbent position in the dental chair with the involved
      sinus on the underside. The saline acts as a vehicle to bring out the implant.
      The festooned aspirator is then introduced into the access window, and the errant
      implant can be successfully brought to the window for retrieval.

PMID- 19400062
TI  - Immediate loading: three cases with up to 38 months of clinical follow-up.
AB  - Since the first report describing the placement of dental implants into fresh
      extraction sockets, there has been an increasing interest in this technique. The
      advantages of immediate implant placement have been reported to include a
      reduction in the number of surgical interventions, potentially decreased alveolar
      bone resorption after tooth loss, and shorter treatment time. Appropriate
      indications, good surgical technique, and the use of a prosthetic protocol have
      resulted in success for immediate loading and immediate implantation. Adverse
      patient-related factors, such as systemic health, a smoking habit, poor oral
      hygiene, presence of a thin biotype, or an infection in the region of the
      extraction, are contraindications for this treatment. Patient satisfaction is
      very high, and some difficulties related to the implantation site in late
      implantations may be eliminated. This article reports on three cases of immediate
      loading with up to 30 months of clinical follow-up.

PMID- 19400063
TI  - Suturing for optimal soft-tissue management.
AB  - Establishing nontension primary wound closure of various soft tissue flaps is
      paramount for optimal postsurgical wound healing. Surgical procedures that
      require clinical flap manipulation, such as those used with traditional
      periodontal therapy, periodontal plastic cosmetic surgery, hard and soft tissue
      regeneration, and the excision of pathologic tissue, also require excellence in
      execution. Also paramount to clinical success is a thorough understanding of the
      various techniques of surgery, suturing, and the materials currently available to
      ensure the desired clinical results. This article will discuss the rationale of
      specific suturing techniques and suture materials to help the clinician obtain
      optimal wound closure.

PMID- 19400064
TI  - Portraits of the pioneers of the American Peptide Society.

PMID- 19400065
TI  - Peptides of life teaching peptide science and art in elementary school.

PMID- 19400066
TI  - Meandering through 50 years of peptide folds and twists.

PMID- 19400068
TI  - Dynamic combinatorial assembly of peptide-rhenium coordinates: application to the
      selection of hCyp-18 inhibitors from a library of 12 x 16 components.

PMID- 19400069
TI  - Dynamic combinatorial assembly of peptide-rhenium coordinates: coordination
      chemistry for generating new analogs of hCyp-18 ligands.

PMID- 19400067
TI  - Stronger and (now) longer synthetic collagen.

PMID- 19400070
TI  - Oxorhenium-mediated cyclization and self-assembly of peptides: a combinatorial
      approach for the selection of new ligands of the human cyclophilin hCyp-18.

PMID- 19400071
TI  - Thieno[3,2-e]diazepinediones and 3-thienylimidazolidinediones syntheses: regio
      controlled ring opening of thiaisatoic anhydride by alpha-amino acids.

PMID- 19400072
TI  - Solid-phase synthesis of phosphinic dipepetide isosteres and beta amino acids via
      activated N-terminal acrylamides.

PMID- 19400073
TI  - Parallel solid-phase synthesis of macrocyclic peptidomimetics using Ru-catalyzed
      ring-closing metathesis and a new application of cross metathesis.

PMID- 19400075
TI  - Development of an efficient solid-phase synthetic methodology to construct a
      combinatorial library of a potent HDAC inhibitor.

PMID- 19400074
TI  - High throughput solid phase parallel synthesis of macrocyclic peptidomimetics.

PMID- 19400076
TI  - A novel hydrogel functionalized with specific peptidomimetic ligands for 2-D and
      3-D cell culture.

PMID- 19400077
TI  - Application of the "libraries from libraries" concept to "one-bead one-compound"
      combinatorial chemistry.

PMID- 19400078
TI  - An appreciation of the scientific life and achievements of Bruce Merrifield.

PMID- 19400079
TI  - The "Bip method" for spectroscopic assignment of the absolute configuration of
      the spin-labelled, cyclic beta2'3-amino acids beta-tOAC and POAC.

PMID- 19400080
TI  - Enzyme mechanism and function of a novel plant PDI involved in the oxidative
      folding of cystine knot defense peptides.

PMID- 19400081
TI  - Biosynthesis of siderophore-peptides, a class of potent antimicrobial peptides
      from enterobacteria, of requires two precursors.

PMID- 19400082
TI  - Post-translational modification and folding of a lasso-type gene-encoded
      antimicrobial peptide require two enzymes only in Escherichia coli.

PMID- 19400083
TI  - Synthesis and 3D-structure of conformationally controlled nucleo-peptides.

PMID- 19400084
TI  - Mixing urea and amide bonds: synthesis and self-organization of new hybrid
      oligomers.

PMID- 19400085
TI  - Optimizing the fold stability of miniprotein sequences.

PMID- 19400086
TI  - Antimicrobial peptides chelating lanthanide ions: the case of trichogin GA IV
      analogues and terbium(III).

PMID- 19400087
TI  - Spectroscopic characterization of the fully-extended, planar, peptide 2.0(5)
      helix based on chiral, Calpha-ethylated, alpha-amino acids.

PMID- 19400088
TI  - Monitoring peptide folding by time-resolved spectroscopies: the effect of a
      single Gly to Aib substitution.

PMID- 19400089
TI  - First homo-peptides undergoing a reversible 3(10)-helix to alpha-helix
      transition.

PMID- 19400090
TI  - Molecular modeling approach to achieving erythropoietin mimetic peptides.

PMID- 19400091
TI  - Conformation analysis of parathyroid hormone residues critical for bioactivity.

PMID- 19400092
TI  - Light-switchable folding/unfolding of the collagen triple helix with azobenzene
      containing model peptides.

PMID- 19400093
TI  - Structural studies of parathyroid hormone analogue with C-terminal aldehyde
      function.

PMID- 19400094
TI  - Synthesis and conformational studies of novel, side-chain protected, L
      (alphaMe)Ser homo-peptides.

PMID- 19400095
TI  - Introduction of N-alkyl residues in proline-rich peptides: effect on SH3 binding
      affinity and peptide conformation.

PMID- 19400096
TI  - Thermodynamic stability and native-state dynamics of porcine pancreatic
      phospholipase A2 studied by 1H NMR spectroscopic measurements.

PMID- 19400098
TI  - Quantitating amino acid beta-strand preferences, turn propensities and cross
      strand interactions in a designed hairpin peptide.

PMID- 19400097
TI  - The amyloidogenic domains of the human serum amyloid A protein--new insights.

PMID- 19400100
TI  - Spectroscopic analysis of synthetic PrP helix2-binding peptide constructs.

PMID- 19400099
TI  - Determinants of fold stabilizing aromatic-aromatic interactions in short
      peptides.

PMID- 19400101
TI  - Unique role of clusters of electrostatic attractions in controlling the stability
      of two-stranded alpha-helical coiled-coils.

PMID- 19400102
TI  - The energetics of weakly polar interactions in model tripeptides.

PMID- 19400103
TI  - Peptidomimetic ligands for the tandem SH2 domain of the Syk protein involved in
      signal transduction.

PMID- 19400104
TI  - Subtilisin kexin isozyme-1 (SKI-1): production, purification, inhibitor design
      and biochemical applications.

PMID- 19400105
TI  - Effects of antifreeze protein fragments on the properties of model membranes.

PMID- 19400106
TI  - Fluorogenic cyclooctapeptides and metal ion sensing.

PMID- 19400107
TI  - The impact of aromatic residues on the tertiary fold of avian pancreatic
      polypeptide.

PMID- 19400108
TI  - An efficient protocol for on-resin, vicinal disulfide formation: applications to
      thioredoxin reductase.

PMID- 19400109
TI  - Potent and selective peptide agonists for human melanocortin receptor 5.

PMID- 19400110
TI  - Synthesis of a library of psi-stylostatins with potential antibacterial activity.

PMID- 19400111
TI  - Mimicking natural globular structures with rigid scaffolds based on adamantane.

PMID- 19400112
TI  - Discovery and optimization of a TRAIL R2 agonist for cancer therapy.

PMID- 19400113
TI  - Novel reactive site loop derived mini-serpin inhibitors of recombinant proprotein
      convertase 4.

PMID- 19400114
TI  - Enzymatic ligation of peptides, peptide nucleic acids and proteins by means of
      sortase A.

PMID- 19400115
TI  - N-methylated cyclic pentapeptides as template structures.

PMID- 19400116
TI  - Cyclic dimers of C-terminal gamma2-MSH analogs as selective antagonists of the
      human sensory nerve-specific receptor (SNSR-4).

PMID- 19400117
TI  - Structure-function relationship study of parathyroid hormone (1-11) analogues
      containing D-AA.

PMID- 19400118
TI  - Selective enzymatic hydrolysis of C-terminal tert-butyl esters of peptides.

PMID- 19400119
TI  - Peptide ligation via the in-situ transformation of an amide into a thioester at a
      cysteine residue.

PMID- 19400120
TI  - Facile synthesis of glucagon-like peptide-1 (GLP-1) mimetics.

PMID- 19400121
TI  - Synthetic peptide vaccines: the quest to develop peptide vaccines for influenza,
      HIV and Alzheimer's disease.

PMID- 19400122
TI  - Rational design of peptidomimetics for class B GPCRs: potent non-peptide GLP-1
      receptor agonists.

PMID- 19400123
TI  - The depsipeptide technique for the solid phase peptide synthesis: from stepwise
      assembly to segment condensation.

PMID- 19400124
TI  - A novel method for the preparation of peptide thioester and its application to
      glycoprotein synthesis.

PMID- 19400125
TI  - Synthesis of 4-arylmethyl-L-histidine analogues for structure-activity studies of
      position 10 of CGRP.

PMID- 19400126
TI  - Solid-phase synthesis of dipeptidic and pseudo-dipeptidic potential NOS
      inhibitors through a side-chain anchoring approach.

PMID- 19400127
TI  - Further development of new deprotection chemistry for cysteine and selenocysteine
      side chain protecting groups.

PMID- 19400128
TI  - A new synthesis of (+)-negamycin and its derivatives as a potential therapeutic
      agent for Duchenne muscular dystrophy treatment.

PMID- 19400129
TI  - Design and synthesis of backbone cyclic phosphopeptides: the IkappaB model.

PMID- 19400130
TI  - Synthesis of modified and hybrid protein derived biopolymers.

PMID- 19400131
TI  - SPPS of the natural product chitinase inhibitor argifin: library generation and
      biological evaluation.

PMID- 19400132
TI  - Development of chemokine receptor CXCR4 antagonists using bio-mimetic strategy.

PMID- 19400133
TI  - Chemical synthesis of the N-terminal cysteine-rich domain of human OX40.

PMID- 19400134
TI  - Stereoselective synthesis of peptidomimetics based on acid-catalyzed ring-opening
      of beta-aziridinyl-alpha,beta-enoates.

PMID- 19400135
TI  - Development of a small molecule peptidomimetic affinity ligand for efficient
      purification of the large protein factor VIII.

PMID- 19400136
TI  - Expression and characterization of recombinant S2 subunit of SARS-coronavirus S
      fusion protein.

PMID- 19400137
TI  - Synthesis of biotinyl-TN14003, anti-HIV peptide amide.

PMID- 19400138
TI  - Making double-minded peptides strong-willed? The side chain impact on the
      backbone conformation of N-methylated cyclic pentapeptides.

PMID- 19400139
TI  - Deprotection of N(in)-formyl group on tryptophan by application of new reagent,
      1,2-dimethylethylendiamine in aqueous solution.

PMID- 19400140
TI  - Racemization-free segment condensation based on the O-acyl isopeptide method:
      toward a chemical protein synthesis on solid support.

PMID- 19400141
TI  - Optimized coupling protocols for the incorporation of cys derivatives during Fmoc
      SPPS.

PMID- 19400142
TI  - Further studies on peptide synthesis at high temperature.

PMID- 19400143
TI  - Preparation of C-terminal modified peptides through alcoholysis and thiolysis
      mediated by metal ions.

PMID- 19400144
TI  - Synthesis and biological activity of amino acid esters of acyclovir.

PMID- 19400145
TI  - Poly-(Prophi[Ch(OAc)CH2]Aib)3 a protected trimer of Pro-Aib hydroxyethylene
      isosteres.

PMID- 19400146
TI  - Fast conventional synthesis of human beta-amyloid (1-42) on the Symphony and
      Prelude.

PMID- 19400147
TI  - Side chain-to-side chain cyclization by intramolecular click reaction--building
      blocks, solid phase synthesis and conformational characterization.

PMID- 19400148
TI  - An efficient approach to synthesize multiple peptides with carboxyl C-termini.

PMID- 19400149
TI  - Synthesis and biological activity of novel alpha-conotoxin analogues
      incorporating substituted proline derivatives.

PMID- 19400151
TI  - Synthesis of pyrrolo[3,2-e] [1,4]diazepin-2-ones as potential gamma-turn
      mimetics.

PMID- 19400150
TI  - Application of triethylsilane and palladium-charcoal-induced reductions in the
      synthesis of Fmoc-glutamic acid analogues.

PMID- 19400152
TI  - Improvements in the chemical synthesis of insulin-like peptides.

PMID- 19400153
TI  - Design and parallel synthesis of new bicyclic small molecules for targeting the
      melanocortin receptors.

PMID- 19400154
TI  - Fully automated fast Fmoc synthesis and on-resin disulfide bridge formation with
      pseudoproline dipeptides on the Prelude.

PMID- 19400155
TI  - Efficient synthesis of protected L-phosphonophenylalanine (Ppa) derivatives
      suitable for solid phase synthesis.

PMID- 19400156
TI  - Allessan CAP--a highly versatile and affordable coupling agent.

PMID- 19400157
TI  - Novel analogues of bifunctional ligands for opioid and melanocortin 4 receptor.

PMID- 19400158
TI  - Fmoc as a probe in peptide purification.

PMID- 19400159
TI  - 1,3,5-Triazepan-2,6-diones as conformationally constrained dipeptide mimetics. In
      silico guided identification of sPLA2 inhibitors.

PMID- 19400160
TI  - Proline-based diketopiperazine-scaffolds.

PMID- 19400161
TI  - Concept and synthetic approach for a kilogram scale synthesis of octa-D-arginine
      amide nonahydrochloride salt.

PMID- 19400162
TI  - Stereoselective synthesis of (3S)- and (3R)-3-hydroxy-3-(2,6-dimethyl-4
      hydroxyphenyl)propanoic acid and its incorporation into a cyclic enkephalin
      analogue.

PMID- 19400163
TI  - Highly selective cyclic hexapeptides antagonist of GPIIb-IIIa by multiple N
      methylation.

PMID- 19400165
TI  - Solid-phase synthesis of 1,3,5-trisubstituted 1,4-diazepin-2-one peptide mimic.

PMID- 19400164
TI  - Synthesis of N-Boc protected hydrazine diacids as key structural units for the
      formation of alpha-helix mimics.

PMID- 19400166
TI  - General solid-phase phosphopeptide proteomis with affinity pull-down.

PMID- 19400167
TI  - Synthesis and peptide coupling of protected pyrrolylalanine.

PMID- 19400168
TI  - Synthesis of aryl sulfamate and phenol small peptide derivatives using a
      multidetachable sulfamate linker strategy.

PMID- 19400169
TI  - Phe-Aib hydroxyethylene dipeptide isostere synthesis.

PMID- 19400170
TI  - Poly (vinyl alcohol)-graft-poly (ethylene glycol) supported hydroxyproline:
      synthesis and application in the enantioselective aldol condensation.

PMID- 19400171
TI  - Microwave-assisted synthesis of rhodamine fluorescent tags.

PMID- 19400172
TI  - A novel family of diketopiperazines as a tool for the study of transport across
      the blood-brain barrier (BBB) and their potential use as BBB-shuttles.

PMID- 19400173
TI  - New perspective in peptide chemistry by N-alkylation.

PMID- 19400174
TI  - Interactions of peptides with single-walled carbon nanotubes.

PMID- 19400175
TI  - Stimuli-responsive peptide self-assembly into well-organized nanofibers.

PMID- 19400176
TI  - pH controlled aggregation morphology of Abeta(16-22): formation of peptide
      nanotubes, helical tapes and amyloid fibrils.

PMID- 19400177
TI  - Immobilization of antimicrobial peptides on reverse osmosis polyamide membranes:
      potential biofilm inhibitors?

PMID- 19400178
TI  - Synthesis of polylactides with side chain functionality: ring-opening
      polymerimerization of a homobislactone prepared from lysine.

PMID- 19400179
TI  - New degradable cationic peptides for modulated gene delivery.

PMID- 19400180
TI  - The Dcpm protecting group is a useful alternative to the Hmb residue.

PMID- 19400181
TI  - Development of a RGDS-peptide modified polyurethane for tissue regeneration.

PMID- 19400182
TI  - Modulating collagen triple-helix stability with 4-chloro, 4-fluoro, and 4
      methylprolines.

PMID- 19400183
TI  - Peptide-chitosan matrix: a new multifunctional biomaterial.

PMID- 19400184
TI  - Effect of phosphorylation on tau aggregation using model peptides and circular
      dichroism studies.

PMID- 19400185
TI  - Peptides for prolonging youth.

PMID- 19400186
TI  - The synthesis of DAMGO-based potential affinity labels with high mu opioid
      receptor affinity and the formation of cyclic O-alkyl thiocarbamates.

PMID- 19400187
TI  - Amino acid derivatives of aporphinic alkaloid glaucine and their antioxidant
      activity.

PMID- 19400188
TI  - Synthesis of cyclic tetrapeptide CJ 15,208: a novel kappa opioid receptor
      antagonist.

PMID- 19400189
TI  - Exploring the relationship between turn geometry and allosteric antagonism of
      peptide mimic ligands for the prostaglandin F2alpha receptor.

PMID- 19400190
TI  - Optimization of the bioconvertion of the angiotensin I converting enzyme
      inhibitors IPP and VPP.

PMID- 19400191
TI  - Tailor made pharmacokinetics of peptides by transient PEGylation.

PMID- 19400192
TI  - Design and synthesis of cyclic arodyn analogues by ring-closing metathesis (RCM)
      for kappa opioid receptor (KOP) antagonists.

PMID- 19400193
TI  - Switch-peptides as folding precursors in self-assembling peptides and amyloid
      fibrillogenesis.

PMID- 19400194
TI  - BioShuttle mediated plasmid transfer--a way to new genetic intervention.

PMID- 19400195
TI  - Incorporation of a novel, fluorescent and helicogenic A-amino acid into
      peptaibols: trichogin GA IV.

PMID- 19400196
TI  - Seeking for alpha-helical propensity in a receptor-bound conformation of glucagon
      like peptide-1.

PMID- 19400197
TI  - Conformational analysis and folding of transmembrane and matrix peptide segments
      of the mitochondrial uncoupling proteins: a comparative study.

PMID- 19400198
TI  - Dynamics study on single and multiple beta-sheets.

PMID- 19400199
TI  - Homotrimeric collagen peptides as model systems for cell adhesion studies.

PMID- 19400200
TI  - Cyclic peptide analogs of laminin active sequences enhance the biological
      activity.

PMID- 19400201
TI  - Hydrophobic peptide segments in soluble proteins competent for membrane
      insertion: role in amyloidogenesis.

PMID- 19400202
TI  - Construction and characterization of melanocortin-2 and -4 receptor chimeras.

PMID- 19400203
TI  - Expression of double transmembrane domain GPCR fragments for biophysical
      analysis.

PMID- 19400204
TI  - Peptide and non-peptide mimetics utilize different pathways for signal
      transduction.

PMID- 19400205
TI  - Structural studies on large fragments of G protein coupled receptors.

PMID- 19400206
TI  - Isolation of the influenza A HA2 C-terminal segment by combination of nonionic
      detergents.

PMID- 19400207
TI  - Molecular imaging and orientational changes of antimicrobial peptides in
      membranes.

PMID- 19400208
TI  - Glycated-CD59 antigen: exploration of synthetic approaches.

PMID- 19400209
TI  - A combination of ligand SAR and receptor site-directed mutagenesis reveals
      requirements for antagonist activity at the melanocortin-3 receptor.

PMID- 19400210
TI  - Conformational effects of cyclic hexapeptides for ion channel properties.

PMID- 19400211
TI  - Synthesis and biological activities of cyclic peptide, hymenamide analogs.

PMID- 19400212
TI  - Monitoring glucagon and glucagon antagonist-mediated internalization: a useful
      approach to study glucagon receptor pharmacology.

PMID- 19400213
TI  - Semi-synthetic strategies to obtain glucosylated MOG to identify antibodies as
      biomarkers in multiple sclerosis disease.

PMID- 19400214
TI  - Photoprobe peptides to map the interactions of angiotensin II with its receptor
      AT1.

PMID- 19400215
TI  - Synthesis and biological activity of transmembrane peptides derived from FPR
      family receptors.

PMID- 19400216
TI  - Incorporation of the unnatural amino acid p-benzoyl-L-phenylalanine (Bpa) into a
      G protein-coupled receptor in its native context.

PMID- 19400217
TI  - Ion channel formation of dimeric peptide enhanced by electrostatic inter-helical
      interactions.

PMID- 19400218
TI  - Temperature-induced ligand contact point variations of the hAT1 receptor and of
      the constitutively active mutant N111G-hAT1.

PMID- 19400219
TI  - Structural changes in the binding pocket of the liganded angiotensin II receptor
      AT1 during activation.

PMID- 19400221
TI  - Vaccine delivery: synthesis and investigation of a highly pure, multi-epitopic
      lipopeptide vaccine candidate.

PMID- 19400220
TI  - Vaccine delivery utilizing liposaccharides.

PMID- 19400222
TI  - Synthesis of mannosylated glycopeptides as components for synthetic vaccines.

PMID- 19400223
TI  - Bradykinin analogues acylated on their N-terminus--some recent development.

PMID- 19400224
TI  - Rationally-designed multivalent architectures for mimicking homotrimers of CD40L,
      a member of the TNF superfamily.

PMID- 19400225
TI  - A strategy for selectively shielding portions of a peptide/protein from immune
      response while maintaining immunogenicity of contiguous epitopes.

PMID- 19400226
TI  - Synthesis of peptide-based vaccines.

PMID- 19400227
TI  - A peptide vaccine based on retro-inverso beta-amyloid sequences fails to elicit a
      cross-reactive immune response.

PMID- 19400228
TI  - Synthesis and application of (Z)-alkene- and (E)-fluoroalkene-dipeptide isosteres
      as cis-amide equivalents.

PMID- 19400229
TI  - Gadd45beta dimerization does not affect MKK7 binding.

PMID- 19400231
TI  - C-terminal amidation on aryl hydrazine resin.

PMID- 19400230
TI  - A glycopeptide-based technique for selective antibody purification.

PMID- 19400232
TI  - Synergy between a lead proline-rich antibacterial peptide derivative and small
      molecule antibiotics.

PMID- 19400233
TI  - Natural mutants of HIV CTL epitopes with enhanced immunogenicity as potential
      vaccine candidates.

PMID- 19400234
TI  - Lipodepsipeptide antibiotic fusaricidin and its analogues. Total solid-phase and
      biological activity.

PMID- 19400235
TI  - Progress toward total solid-phase synthesis of depsipeptide antibiotic katanosin
      B.

PMID- 19400236
TI  - Determination of the minimal fusion peptide of HIV, SIV and BLV fusion
      glycoproteins.

PMID- 19400237
TI  - Development of a novel fusion inhibitor against T-20-resistant HIV-1.

PMID- 19400238
TI  - Epsilon-peptide chimeras as novel antimicrobials.

PMID- 19400239
TI  - Chemical modifications of short antimicrobial peptides from insects and
      vertebrates to fight multi-drug resistant bacteria.

PMID- 19400240
TI  - Isolation of peptides from rat tissues: peptidomics vs. degradomics.

PMID- 19400241
TI  - Multivalent peptidomimetics for tumor targeting.

PMID- 19400242
TI  - Comparison of [18F]FBA and [18F]FPyMe as peptide radiolabeling agents of PEPHC1
      for PET imaging of EGFRvIII.

PMID- 19400243
TI  - Carbohydrated [99mTc(CO)3](NalphaHis)Ac-bombesin(7-14) analogs.

PMID- 19400244
TI  - A synthetic peptide approach for elucidating the points of natural auto-antibody
      reactivity to proteolytic fragments of human IgG.

PMID- 19400245
TI  - Heterobivalent ligands crosslink multiple cell-surface receptors--a step towards
      personal medicine.

PMID- 19400246
TI  - Development of polyvalent peptide-conjugated magnetic nanoparticles for targeted
      in-vivo imaging of micro-thrombi.

PMID- 19400247
TI  - Design, selection and binding mechanism of bivalent miniproteins targeting human
      thrombin.

PMID- 19400248
TI  - Quenched fluorescent peptide substrates as tools for the discovery of novel
      cardiovascular disease biomarkers.

PMID- 19400249
TI  - Solid phase synthesis and analysis of Amadori peptides.

PMID- 19400250
TI  - Design of hetero-bivalent polypeptides as kinetics-based sensors for high
      sensitivity detection of weak molecular interactions.

PMID- 19400251
TI  - Monitoring of native chemical ligation by surface plasmon resonance.

PMID- 19400252
TI  - Studies for identification of the minimal epitope(s) mimicked by the synthetic
      glucopeptide CSF114(Glc).

PMID- 19400253
TI  - Synthesis of bivalent MSH ligands and evaluation of their binding to hMC4R using
      MSH lanthaligand.

PMID- 19400254
TI  - Synthesis of organometallic glycopeptides and electrochemical studies to detect
      autoantibodies in multiple sclerosis patients' sera.

PMID- 19400255
TI  - Tumor imaging with tetrabranched neurotensin.

PMID- 19400256
TI  - A new and selective radiolabeled alphavbeta3 peptide antagonist as tracer in
      tumor diagnosis.

PMID- 19400257
TI  - Ribose building block for the synthesis of glycopeptides for fishing out
      antibodies in autoimmune diseases.

PMID- 19400258
TI  - Design, synthesis and pharmacological characterization of fluorescein-derived
      endothelin antagonists Bq-123 and Bq-788.

PMID- 19400259
TI  - Peptide antagonists of the PED-hPLD1 binding.

PMID- 19400260
TI  - In vivo imaging using tissue specific near infrared fluorescent peptide
      conjugate, c[RGDyK(HiLyte Fluor 750].

PMID- 19400261
TI  - Photoinduced intramolecular covalent bond formation in structurally rigid -Bpa
      (spacer)-Met hexapeptides.

PMID- 19400262
TI  - Evaluation of chemically and enzymatically prepared cross-linked BNP fragments.

PMID- 19400263
TI  - Monitoring of MMPs activity in vivo, non-invasively, using solubility switchable
      MRI contrast agent.

PMID- 19400264
TI  - 99mTc-labeled Ac-DEVD peptides as a substrate for measuring caspase activity.

PMID- 19400265
TI  - PepLook: an innovative in silico tool for determination of structure,
      polymorphism and stability of peptides.

PMID- 19400266
TI  - The effects of the EW--peptide optical and chemical isomers on the hemopoietic
      stem cells in intact and irradiated mice.

PMID- 19400267
TI  - N-(Fluorenyl-9-methoxycarbonyl)amino acid amide derivatives as a new class of
      anti-cancer agents.

PMID- 19400268
TI  - Opportunities and challenges of developing peptide drugs in the pharmaceutical
      industry.

PMID- 19400269
TI  - Inhibition of pathogenically-related morphologic transition in Candida albicans
      by disrupting Cdc42 binding to its effectors.

PMID- 19400270
TI  - Synthesis and pharmacological evaluation of highly potent [Dmt1]DALDA analogs.

PMID- 19400271
TI  - Protease-resistant glucagon like peptide-1 analogs with long-term anti-diabetes
      type 2 activity.

PMID- 19400272
TI  - The discovery and development of a natural combinatorial peptide template: the
      cyclotides.

PMID- 19400274
TI  - Facile synthesis of hydrocarbon-stapled peptides.

PMID- 19400273
TI  - Cyclic peptides as VEGF receptor antagonist.

PMID- 19400275
TI  - Isolation of angiotensin I converting enzyme inhibitory peptides from a fish by
      products hydrolysate Tensideal.

PMID- 19400276
TI  - Novel melanocortin-4 receptor agonists that decrease food intake and body weight.

PMID- 19400277
TI  - GHS-1a agonists that effectively stimulate food intake and body weight gain.

PMID- 19400278
TI  - Conformation-activity relationships of cyclo-constrained mu/delta opioid agonists
      derived from the N-terminal tetrapeptide segment of dermorphin/deltorphin.

PMID- 19400279
TI  - Deltorphin analogs restricted via a urea bridge: structure and opioid activity.

PMID- 19400280
TI  - Synthesis and characterization of dimeric venom peptides.

PMID- 19400281
TI  - Glycosyl-enkephalins: synthesis and binding at the mu, delta & kappa opioid
      receptors. Antinociception in mice.

PMID- 19400282
TI  - Agonists and partial antagonists acting on the leptin--leptin receptor interface.

PMID- 19400283
TI  - Effect of 4-fluoro-L-proline on the SH3 binding affinity.

PMID- 19400285
TI  - Analogues of arginine vasopressin modified at position 2 with proline
      derivatives: selective antagonists of oxytocin in vitro.

PMID- 19400284
TI  - Analogues of arginine vasopressin modified in the N-terminal part of the molecule
      with pipecolic acid isomers.

PMID- 19400286
TI  - Multimeric peptides as agonists of the erythropoietin receptor.

PMID- 19400287
TI  - Synthesis and in vitro pharmacological profile of potent and selective peptidic
      V1a receptor agonists.

PMID- 19400288
TI  - Discovery of a ligand that compensates for decreased endogenous agonist potency
      of melanocortin-4 receptor polymorphisms identified in obese humans.

PMID- 19400289
TI  - High-affinity FGFR2 binding peptides derived from the native epitope of the KGF
      ligand.

PMID- 19400290
TI  - Application of intramolecular migration reaction in peptide chemistry to chemical
      biology, chemical pharmaceutics and medicinal chemistry.

PMID- 19400291
TI  - Synthesis & biological evaluation of PYY(3-36) analogs substituted with alanine.

PMID- 19400292
TI  - Development of mu/delta opioid ligands: enkephalin analogues containing 4
      anilidopiperidine moiety.

PMID- 19400293
TI  - Factors that affect dissociation degree of strong aggregated peptide chains when
      bound to a polymer or free in solution.

PMID- 19400294
TI  - Development of AEZS-115 (ZEN-019) by optimization of structurally unique, orally
      active, peptidomimetic GnRH antagonists.

PMID- 19400295
TI  - Synthesis and solid-phase application of suitably protected gamma-hydroxyvaline
      building blocks.

PMID- 19400296
TI  - Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors:
      new leads for antifungal and anti-inflammatory drugs.

PMID- 19400297
TI  - Synthesis of biotin-tagged diketopiperazine-based anti-microtubule agents and
      tubulin photoaffinity labeling.

PMID- 19400298
TI  - Study on interactions of oligo(tyrosine sulfate)s with synthetic heparin-binding
      peptides by affinity chromatography and MALDI-TOF-MS.

PMID- 19400299
TI  - Fallaxin analogues with improved antibacterial activity.

PMID- 19400301
TI  - Peptide-lisinopril conjugates: design, synthesis and biological activities.

PMID- 19400300
TI  - Alkene/alkane-bridged mimics of the lantibiotic nisin: toward novel peptide-based
      antibiotics.

PMID- 19400302
TI  - Novel bifunctional peptides as opioid agonists and NK-1 antagonists.

PMID- 19400303
TI  - Anti-HIV dendrimeric peptides.

PMID- 19400304
TI  - Ago-antagonists for G protein-coupled peptide hormone receptor by modifying the
      agonist's signalling domain.

PMID- 19400305
TI  - Model of intermolecular interactions between high affinity phosphopeptides and
      Stat3.

PMID- 19400306
TI  - Inhibition of Stat3 by cell-permeable peptidomimetic prodrugs targeted to its SH2
      domain.

PMID- 19400307
TI  - Synthesis and biological activity of conformational restricted galanin fragments.

PMID- 19400308
TI  - Interaction of membrane mimetic vesicles with the antimicrobial peptide gomesin
      and its analogues.

PMID- 19400309
TI  - Limited structure-activity relationships for carboxy and aminoterminal
      substitutions of peptide YY 25-36.

PMID- 19400310
TI  - Cysteine based PNA (CPNA): design and synthesis of novel CPNA monomers.

PMID- 19400311
TI  - Synthesis and biological activity of nicotianamine and analogues.

PMID- 19400312
TI  - The active site specificity of angiotensin II converting enzyme 2 investigated
      through single and multiple residue changes and beta-amino acid substrate
      analogs.

PMID- 19400313
TI  - Effects of net charge and the number of positively charged residues on the
      biological activity of amphipathic alpha-helical cationic antimicrobial peptides.

PMID- 19400314
TI  - Action of Bauhinia-derivated compounds on Callosobruchus maculatus development.

PMID- 19400315
TI  - Positively charged gramicidin A based peptides form two types of membrane
      channels.

PMID- 19400316
TI  - Effects of tumor-associated mutations in the p53 tetramerization domain on
      oligomerization state and transcriptional activity.

PMID- 19400317
TI  - Self-association regions in the CARD of Bcl-10.

PMID- 19400318
TI  - GHRP-2 attenuates burn-induced dysfunctions in rodents.

PMID- 19400319
TI  - Peptides binding the type E immunoglobulins.

PMID- 19400320
TI  - Evolution of the synthetic process to prepare the tripeptide segment of ABT-510.

PMID- 19400321
TI  - Retrocyclin-2: a potent anti-HIV theta-defensin that forms a cyclic cystine
      ladder structural motif.

PMID- 19400322
TI  - Isothermal titration calorimetry and inhibition of platelets aggregation by [D
      Phe/(transcinnamoyl)-Pro-D-Arg-P1'-CONH2] peptides inhibitors of thrombin.

PMID- 19400323
TI  - Trypsin stability of lysine-peptoid hybrids.

PMID- 19400324
TI  - A comparative examination of two Fmoc removal reagents for process improvement to
      produce peptide drugs.
AB  - The importance of peptides as therapeutics has been recognized since they were
      found responsible for a wide variety of biological functions. The recent approval
      of peptide drugs such as Byetta (Amylin Pharmaceuticals, Inc.), Fuzeon (Hoffman
      LaRoche Inc.), Integrelin (CDR Therapeutics, Inc.), Natrecor (SCIOS Inc.), Symlin
      (Amylin), Teriparatide, and Ziconotide, etc., which demonstrated applications for
      treatment of such problems as bone metabolism disorders, cardiovascular diseases,
      diabetes, viral infections and severe chronic pain control, has further endorsed
      the growing interest in peptides as a potential drug. This growing trend for
      peptide drugs has drawn our attention for their production in a cost-effective
      manner. To do so, the improvement in the quality of crude peptides during
      synthesis, the most critical parameter in the process, is important to prevent
      yield losses during the more expensive purification step. To accomplish it, we
      decided to examine the efficacy of the commonly used nucleophilic base piperidine
      and non-neucleophilic base DBU (1,8-Diazabicyclo[5.4.0]undec-7-ene) for the
      complete removal of Fmoc group during the synthesis of peptides. According to our
      investigation, application of piperidine was found more effective than DBU in
      solid phase synthesis. Details of the investigation will be discussed.

PMID- 19400325
TI  - Bicyclic organo-peptides as models for carbohydrate binding proteins.

PMID- 19400326
TI  - Impurity rejection in the crystallization of ABT-510 as a method to establish
      starting material specifications.
AB  - Understanding impurity rejection in a drug substance crystallization process is
      valuable for establishing purity specifications for the starting materials used
      in the process. Impurity rejection has been determined for all known ABT-510
      impurities and for many of the reasonable & conceivable impurities. Based on this
      study, a very high purity specification (e.g., > 99.7%) can be set for ABT-510
      with a high level of confidence.

PMID- 19400327
TI  - Spatially defined peptide-polymer biotherapeutic synthesis on novel cross-linked
      beads with 'spatially tunable' and 'isolated' functional sites.

PMID- 19400328
TI  - Supramolecular aggregates derivatized by CCK8 peptide as selective nanocarriers
      for drug delivery.

PMID- 19400329
TI  - The role of cell penetrating peptides (CPPs) in membrane lipid phase behavior: a
      novel aspect elucidating peptide-mediated delivery.

PMID- 19400330
TI  - Factors that influence oral bioavailability; a cathepsin K inhibitor for human
      studies.

PMID- 19400331
TI  - Injectable biodegradable polymer depots for minimally invasive delivery of
      peptides and proteins.

PMID- 19400332
TI  - Nursing applicants to face compassion test.

PMID- 19400333
TI  - First response to PM's review.

PMID- 19400334
TI  - Do we need a national approach to alcohol advice?

PMID- 19400336
TI  - NPSA issues guidance to reduce risks linked to bowel-cleansing solutions.

PMID- 19400335
TI  - Delivering mental health awareness training to police officers.
AB  - Police officers regularly come into contact with people with mental health
      problems but receive relatively little training on the issue. This article
      outlines an initiative to deliver awareness training to officers, and explores
      the benefits of such programmes. It also gives details of the evaluation carried
      out.

PMID- 19400337
TI  - Emergency oxygen delivery in adults 1: updating nursing practice.
AB  - The first in this two-part unit discusses new British Thoracic Society guidance
      on using emergency oxygen in adults. This is the first national guidance on this
      area and the implications for possible changes to practice are highlighted here.
      This part outlines the philosophy behind the guideline, the differences between
      hypoxaemic and hypercapnic patients and essential assessments for critically ill
      patients who need emergency oxygen. It also discusses using this therapy for
      patients with lung cancer in acute situations.

PMID- 19400338
TI  - Does oxygen need to be prescribed?

PMID- 19400339
TI  - New NICE rheumatoid arthritis guideline offers a key role for specialist nurses.

PMID- 19400340
TI  - Are breathing exercises an effective strategy for people with asthma?
AB  - BACKGROUND: The effect of breathing techniques on asthma symptoms and disease
      control is uncertain. AIM: To investigate whether physiotherapist-taught
      breathing exercises can improve asthma control and reduce the condition's impact
      on patients' quality of life. METHOD: A randomised controlled trial comparing
      breathing training with asthma education (control for non-specific effects of
      healthcare professionals' attention) was carried out. RESULTS: One month after
      the intervention, both groups showed similar improvements in asthma quality-of
      life questionnaire scores but, at six months, there was a significant difference
      between groups in favour of breathing training. There was also a significant
      difference in anxiety and depression scores in favour of breathing training at
      six months. DISCUSSION AND CONCLUSION: This study found that adult patients with
      asthma who were taught breathing exercises showed improvements in quality of
      life, symptoms and psychological well-being after six months. Breathing exercises
      may have a role in helping the many people treated for asthma in general practice
      who have symptoms despite inhaled treatment.

PMID- 19400341
TI  - Nursing must make sure it is ready to take on increased control and influence.

PMID- 19400342
TI  - On the Conservatives' vision for health visiting.

PMID- 19400344
TI  - Managers will lead NHS changes.

PMID- 19400345
TI  - Commission aims to put nurses 'at the heart of world-class NHS'.

PMID- 19400347
TI  - Wake-up call for diabetes.

PMID- 19400346
TI  - The commission is a unique opportunity to give nurses the influence they deserve.

PMID- 19400348
TI  - Does new guidance on needle exchange go far enough?

PMID- 19400349
TI  - Setting up mobile clinics to improve young people's sexual health.
AB  - Increasing the amount of outreach work in sexual health is key to tackling the
      rise in sexually transmitted infections in the .K. This article describes some of
      the research on the benefits of outreach work. It then outlines how mobile sexual
      health clinics were set up to help young people engage with services and reduce
      the incidence of STIs.

PMID- 19400350
TI  - Transient loss of consciousness 2: patient pathways and the nurse's role.
AB  - This second article of a two-part unit explores the assessment and treatment of
      patients with transient loss of consciousness. It explains the importance of
      taking a thorough medical history, nurses' role in treating these patients, and
      the various diagnostic tests and management options.

PMID- 19400351
TI  - What action should be taken if a nurse is worried about a deteriorating patient?

PMID- 19400352
TI  - The challenge of care--managing a confused patient in an inpatient setting.
AB  - This article looks at the issues around capacity and consent, focusing
      particularly on how nurses should assess the capacity of confused patients to
      make decisions about their treatments. It covers the legal framework, including
      the Mental Capacity Act, within which nurses must care for patients who, due to
      illness or incapacity, are unable to understand, consent to or cooperate with
      treatment. It emphasises the importance of training to give nurses the knowledge
      to assess risk and document it correctly, and have the confidence to be able to
      justify their actions if necessary.

PMID- 19400353
TI  - On the key role of nurses in incident reporting.

PMID- 19400354
TI  - 'Nursing values make health care meaningful'.

PMID- 19400355
TI  - Welcome to the Nursing Times special supplement on the productive series.

PMID- 19400356
TI  - The productive series will allow staff to revolutionise the NHS.

PMID- 19400357
TI  - 'This is a phenomenon'.

PMID- 19400358
TI  - The six lessons for successful implementation.

PMID- 19400360
TI  - The productive operating theatre.

PMID- 19400359
TI  - Putting it into practice.

PMID- 19400361
TI  - Working with nurses in the community.

PMID- 19400362
TI  - Less talk, more action.

PMID- 19400363
TI  - Timely reminder of care standards--but is the message strong enough? Interview by
      Erin Dean.

PMID- 19400364
TI  - Where is measles likely to strike?

PMID- 19400365
TI  - Life-changing research.
AB  - Landmark nursing research has inspired nurse leaders to take their own pioneering
      steps.

PMID- 19400366
TI  - Delivering spiritual care. Interview by Lynne Pearce.
AB  - Spirituality is often confused with religion but the two are by no means
      interchangeable. For nurses it is about how they talk to patients.

PMID- 19400367
TI  - No victory in death.

PMID- 19400368
TI  - Development of entrepreneurial activity in nurse education.
AB  - The provision of health care and healthcare education in the UK is undergoing
      rapid change and development, and is subject to intense market forces. A
      reduction in the amount of money being spent on nurses' education and training,
      together with changes in working practices in health care, are affecting the
      provision of healthcare education significantly. This article gives an overview
      of the changes influencing providers of pre and post-registration healthcare
      education, and describes how education providers are generating income through
      enterprise activity.

PMID- 19400369
TI  - Brief interventions to reduce tobacco-related diseases.
AB  - Tobacco-related diseases are a major threat to public health in the UK. High
      levels of morbidity and mortality for users of tobacco and those exposed to
      tobacco smoke are associated with such diseases. This article outlines a
      socioeconomic overview of tobacco use in the UK and the associated risk factors.
      A summary of brief interventions is presented, which has the potential to form
      the core elements of a community-based smoking cessation initiative and reduce
      the threat of tobacco-related diseases to public health.

PMID- 19400370
TI  - Pulmonary embolism: identification, clinical features and management.
AB  - Pulmonary embolism commonly results from blood clots in the venous system which
      lodge in and block a pulmonary blood vessel. Typical presenting features include
      chest pain, palpitations, breathing difficulties and haemoptysis. It is a common
      and potentially fatal condition. Timely diagnosis and treatment can significantly
      reduce morbidity and mortality rates and nurses need to be aware of the risk
      factors associated with the condition to identify high-risk patients.

PMID- 19400371
TI  - Bronchiectasis.

PMID- 19400372
TI  - Weighing up research.

PMID- 19400373
TI  - Primary source of support.

PMID- 19400374
TI  - Stand out from the rest.

PMID- 19400375
TI  - Little bodies, big challenges.

PMID- 19400376
TI  - Answers to $64 million question were thought-provoking.

PMID- 19400377
TI  - The power of books.

PMID- 19400378
TI  - Pain reliever.

PMID- 19400379
TI  - Read this and call me in the morning.

PMID- 19400380
TI  - Rx: read to your children.

PMID- 19400381
TI  - Baby monitors.

PMID- 19400383
TI  - Caring for Lucy.

PMID- 19400382
TI  - Living proof.

PMID- 19400384
TI  - Hib returns.

PMID- 19400385
TI  - Ending an epidemic: physicians' role in primary caries prevention.

PMID- 19400386
TI  - Two birds, one stone: cover the uninsured by fixing Medicare.

PMID- 19400387
TI  - Transitioning adolescents to adult care: putting theory into practice.
AB  - Because many children with complex health conditions now live well into
      adulthood, they will reach an age when they can no longer be cared for in a
      pediatric practice. In order to help patients, families, and physicians prepare
      for and make the transition from pediatric to adult care, a group of concerned
      providers and family members met at Children's Hospitals and Clinics of Minnesota
      to discuss the issues involved. They developed a document, the "Roadmap for
      Transitioning Adolescents from a Pediatric to an Adult Practice," to help with
      the process and also identified barriers to accomplishing a smooth transition.
      This article describes the issues addressed by the group, how the Roadmap can be
      applied to children with various health needs, and what still needs to be done to
      help the process go more smoothly for patients and physicians.

PMID- 19400388
TI  - Pediatric depression: issues and treatment recommendations.
AB  - Major depressive disorder in adolescents is associated with severe consequences
      including suicide. Early intervention is crucial for preventing such outcomes.
      Parents may be reluctant to pursue antidepressant therapy for their children
      because of concerns about 1) a potential risk of increased suicidal ideation and
      2) the effect of these medications on brain development. This article discusses
      the current data about potential risks associated with antidepressant use in
      children and adolescents versus the risk of untreated illness on their
      development. It also reviews recent research that suggests combination treatment
      involving antidepressant medications such as fluoxetine and cognitive behavioral
      therapy may be particularly helpful to patients who show poor response to only
      one of these treatments.

PMID- 19400389
TI  - Neurofibromatosis type 1: update on a common genetic condition.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition
      affecting the skin, peripheral nervous system, and skeletal system. Half of all
      cases are inherited from a parent. The disease, which often manifests in
      childhood, affects an estimated 1 in 3,000 people, making it likely that
      physicians in Minnesota will encounter a patient with NF1.This article describes
      the diagnostic criteria for NF1 and the use of genetic testing for diagnosis; it
      also includes information about resources for diagnosing and treating children
      with the condition.

PMID- 19400390
TI  - A call to action.

PMID- 19400391
TI  - Nursing in the garden laboratory and kitchen clinic.

PMID- 19400392
TI  - Holistic nursing in the homecare and hospice setting.

PMID- 19400393
TI  - Bedside music in the hospital.

PMID- 19400394
TI  - Practicing aromatherapy in a busy community hospital.

PMID- 19400395
TI  - A journey across practice settings: following my call.

PMID- 19400396
TI  - Using healing energy in a hospital spa.

PMID- 19400397
TI  - Palliative care enhances quality of life.

PMID- 19400398
TI  - Private practice: the joys and risks.

PMID- 19400399
TI  - Using aromatherapy to reduce nursing students' stress: a pilot study.

PMID- 19400400
TI  - Trusting the process. Holding the vision.

PMID- 19400402
TI  - In gratitude: Charlie.

PMID- 19400401
TI  - Richard Cowling III: 2008 holistic nurse of the year.

PMID- 19400403
TI  - Near-total functional recovery achieved in partial cervical spinal cord injury
      (50% injury) after 3 years of coordination dynamics therapy.
AB  - The present paper explains how an 18 year-old boy, who suffered an incomplete
      spinal cord injury (SCI) at the Cervical 5/6 levels, could achieve a near
      complete recovery within 3 years of coordination dynamics therapy (CDT). The
      anatomically incomplete SCI was evident on MRI (Magnetic Resonance Imaging) which
      showed that 50% of the cord tissue was destroyed at the injury site. The
      administered CDT included the training of crawling, walking, running, jumping,
      and exercising on special CDT devices. Now 21 years old, this chronically injured
      young man cannot only walk independently, but he can also run and jump. He has
      attained full bladder control and is off all medications. The underlying
      mechanism contributing to this excellent recovery will have to be explained in
      the framework of the System Theory of Pattern Formation. In this framework the
      clinical improvement can be quantified in terms of coordination dynamics values,
      behavioural description of movement performance, analysis of motor patterns, and
      surface electromyography (sEMG) recorded during the movements. The impaired
      ability of the injured nervous system to self-organize is evidenced by
      deteriorated motor programs recorded with sEMG, unstable movement performances,
      and asymmetric attractor layouts in coordination dynamics recordings. On the
      other hand, the improvement of motor programs after CDT could also be measured by
      surface EMG, including measurements of antagonistic action of muscles and also by
      the improvement of the mean stability of motor patterns. These indicators of
      improving motor programs could be correlated with clinical improvement in certain
      motor performances like running and jumping. The recovery could mainly be
      achieved through a functional reorganisation as was indicated by the absence of
      significant improvement in the power of the quadriceps femoris muscles. The
      performances of turning on the special CDT device against high loads were
      diagnostic for the extent of repair of the integrative functions of the CNS. The
      cure of urinary bladder function is probably attributable to learning transfer
      from stereotyped, coordinated, integrative movements to the neural networks
      involved in bladder control. Since the patient received sub-optimal CDT, it took
      more than 3 years for the recovery. It appears that the repair of the integrative
      functions of the CNS need longer periods of time. But training such integrative
      movements is pivotal in inducing learning transfer from motor patterns to
      autonomic functions that resulted in the cure of urinary bladder function.

PMID- 19400404
TI  - Leg muscles recruitment pattern in soccer players and active individuals during
      isometric contractions.
AB  - This study aimed to compare the torque, torque ratio (Hamstrings: Quadriceps -
      H:Q), electromyographic (EMG) activity and EMG ratio (knee flexors: knee
      extensors EMG) in soccer players (SG, N = 10) and active subjects (AG, N = 10).
      Subjects performed three maximal voluntary isometric knee extensions and flexions
      at 45 degrees and 90 degrees to determine the peak torque and EMG activity.
      Torque and EMG activity of the knee flexor (biceps femoris [BF] and
      semitendinosus [ST]) were divided by the torque and EMG activity of the knee
      extensor (vastuls lateralis [VL] and rectus femoris [RF]) to calculate torque
      ratios (H:Q) and EMG ratios (BF:VL, BF:RF, ST:VL, ST:RF). The flexion torque was
      significantly higher for SG (p < 0.05) in 45 degrees and 90 degrees. EMG activity
      for SG was significantly higher in agonist contractions for VL, RF and ST and
      significantly lower in antagonist contractions for RF and ST when compared to AG.
      Torque and EMG ratios were similar between groups and there were good
      correlations between torque ratio and BF:VL ratio (r = 0.71, p = 0.02) and BF:RF
      ratio (r = 0.81, p = 0.004) at 45. The EMG results could overestimate the joint
      balance calculated using torque ratios. Differences in recruitment pattern
      between soccer players and non-athletes can be related to the training routines
      and the EMG ratios presents applicable in trained populations.

PMID- 19400405
TI  - A novel signal processing method using system identification for underwater
      surface electromyography.
AB  - PURPOSE: Currently, to record underwater surface electromyography (EMG),
      electrodes are covered with waterproof tape. For short-term measurement,
      waterproof tape prevents electrical leakage. However, during long-term
      measurement, water or sweat can contact the electrodes, changing the measurement
      conditions and gradually affecting the EMG data. The purpose of present study was
      to devise a novel method for prolonged underwater EMG recording, which estimate
      dry-land EMG from underwater EMG recorded by non-waterproofed electrodes using
      system identification techniques. METHOD: One healthy male participated in this
      study. System identification was used to convert underwater EMG signals to the
      estimated dry-land signals. Transfer functions were derived using two pairs of
      surface recording electrodes on the same muscle in parallel. System input was the
      EMG recorded using non-waterproofed electrodes; the output was the signal
      recorded underwater using waterproofed electrodes (supposed to be the same as dry
      land signals). To examine the validity of the present method, three experiments
      were conducted. RESULT: There was a high positive correlation between the
      estimated dry-land EMG based on the non-waterproofed electrodes and the EMG
      obtained using waterproofed electrodes. To test the validity of long-term
      recording using the novel method, the estimated dry-land EMG signals were
      measured during 30 minutes of underwater stepping and were stable. CONCLUSION:
      The novel method using non-waterproofed electrodes with system identification
      techniques eliminated the effect of changes in measurement conditions and appears
      effective for long-term, underwater surface EMG recording.

PMID- 19400406
TI  - A task failure has no effect on the electromechanical delay of the peroneus
      longus.
AB  - OBJECTIVE: Ankle inversion injuries represent the most common trauma sustained by
      athletes. Muscle fatigue from activity may contribute to a delay in the response
      of the ankle proprioceptors and dynamic restraints during unexpected inversion.
      The purpose of this investigation was to determine if the electromechanical delay
      (EMD) of the peroneus longus is influenced by a task failure exercise. SUBJECTS:
      Sixteen subjects (age 20 +/- 1.1 y; mass 71.6 +/- 12.5 kg; height 173.0 +/- 8.7
      cm; 9 male, 1 female) with no lower extremity injuries reported for data
      collection. MEASUREMENTS: Data were collected from each subject's dominant leg
      using surface electromyography (EMG). Electrodes were applied over the peroneus
      longus (PL) using a standard protocol. A stimulating electrode was applied to the
      common peroneal nerve. Subjects were placed in a monopedal stance on a force
      platform. A low amplitude, short duration stimulus was applied to the common
      peroneal nerve. The EMG was used to determine timing of the M wave and the force
      platform was used to determine the onset of foot pronation. Once 6 trials were
      recorded, subjects completed 2 sets of an isotonic activity that isolated the
      peroneals. The task was completed to failure for each set. Immediately following
      the task failure exercise, subjects returned to the force platform for 6
      additional trials recorded as before. Analysis of data was performed by
      determining the onset of the M wave as the beginning of positive EMG activity
      following the end of the imposed stimulus response. This point was superimposed
      on the force platform curve and the point at which a 10 N.m force change occurred
      was used to calculate the EMD (time difference between the force platform
      indicator and the M wave indicator). RESULTS: Average EMD prior to the task
      failure exercise was 13.35 +/- 3.47 ms. Following the task failure exercise, the
      average EMD was 12.67 +/- 3.86 ms. A paired samples t test revealed no
      significant differences with regard to EMD between pre- and post-task failure
      exercise for the PL (p = 0.448). CONCLUSION: We concluded that the task failure
      exercise did not affect the electromechanical delay of the PL.

PMID- 19400408
TI  - Electromyography study of skeletal muscle during locomotion in a treadmill test:
      a case study.
AB  - Recent researches are trying to rebuild an important human history of its posture
      and march from the anatomic function evolutions of the skeletal muscle (10, 11,
      9, 2). The aim of this study is to verify electromyography data of muscles recto
      femoris, iliocostalis, gluteus maximus, erector spinae, semitendinosus during
      human locomotion in two different treadmill protocols (Naughton and Bruce). Data
      analyses, such as mean was calculated on the Word Office Excel. For
      electromyography data Aqdata program was utilized. Muscles rectus femoris,
      iliocostalis, gluteus maximus, erector spinae, semitendinosus were studied using
      electromyography analyses during human locomotion in treadmill. A number of six
      individuals was selected for this research. For the Bruce test all individuals
      ended there participation in the test on the fourth or fifth stage. For the
      Naughton test all individuals completed the 21 minutes walking. For the Bruce
      test all the muscle had higher RMS mean when compared with Naughton test, due the
      effort level for each test.

PMID- 19400407
TI  - Electromyographic activity of knee stabilizer muscles during six different
      balance board stimuli after anterior cruciate ligament surgery.
AB  - The purpose of this study was to compare the electrical activity of the knee
      stabilizers, in patients with ACL (anterior cruciate ligament) reconstructed and
      uninjured individuals during different balance board stimuli. Eleven post-surgery
      individuals and eleven uninjured controls participated in the study. The muscular
      activity of the vastus medialis obliquus, vastus lateralis, semitendinosus,
      biceps femoris and gastrocnemius medial were analyzed by surface electromyography
      during the execution of six different balance board activities. All
      electromyographic data were reported as percentage of RMS mean values obtained in
      maximal voluntary isometric contractions (MVIC) for each muscle. When comparing
      the individuals with ACL reconstructed and uninjured controls, minor
      electromyographic activity was observed (MVIC %) for all the muscles in the
      surgery group (P < 0.05), however, when comparing each exercise between the
      groups, a statistically significant difference for vastus lateralis was
      demonstrated in the floor exercise (P = 0.02) and for gastrocnemius on the round
      board (P = 0.04). Individuals ACL reconstructed presented a decrease in muscular
      activity during different balance board stimuli, which suggests that compensatory
      alterations after ACL may still exist even after a surgery to repair an ACL
      rupture.

PMID- 19400409
TI  - Sex steroidal modulation of collagen metabolism in uterine leiomyomas.
AB  - Uterine leiomyoma is a fibrotic disease that contains abundant extracellular
      matrix (ECM) components, particularly collagen fibrils. Aberrant ECM metabolism
      has been thought to contribute to the pathogenesis of uterine leiomyomas.
      However, it remains poorly understood whether ovarian sex steroid hormones
      modulate collagen metabolism in uterine leiomyomas. More recently, a few articles
      have demonstrated the differential effects of ovarian sex steroids, selective
      estrogen receptor modulators (SERMs), and selective progesterone receptor
      modulators (SPRMs) on the induction of the ECM-remodeling enzymes and collagen
      synthesis in uterine leiomyoma cells. Sex steroids may act to up-regulate
      collagen synthesis, whereas SERMs and SPRMs down-regulate collagen synthesis.
      Further study will be needed to clarify the precise mechanism underlying
      steroidal regulation of collagen synthesis in uterine leiomyomas.

PMID- 19400410
TI  - Septoplasty allows successful delivery in a primary aborter with six previous
      first trimester miscarriages.
AB  - PURPOSE: To demonstrate that septoplasty can correct a problem of recurrent
      miscarriage. METHODS: The patient was a primary aborter with a history of six
      consecutive miscarriages. Septoplasty by hysteroscopy/laparoscopy was performed.
      The septum was diagnosed by 3D sonohysterography. RESULTS: She delivered a
      healthy live baby at 36 weeks. CONCLUSION: This case clearly demonstrates that
      sometimes the uterine septum plays an important role in recurrent miscarriage and
      that septoplasty can improve the chances of successful delivery. The case also
      shows that a definitive diagnosis of a bicornuate uterus by HSG and/or MRI can
      not be made.

PMID- 19400411
TI  - Pregnancy outcome after treatment of cervical intraepithelial neoplasia by the
      loop electrosurgical excision procedure and cold knife conization.
AB  - PURPOSE OF INVESTIGATION: The aim of this study was to evaluate the effect of
      LEEP and cold-knife conization on the outcome of subsequent pregnancy in a
      tertiary public hospital. METHODS: One hundred and ninety-nine patients met the
      inclusion criteria (age between 18 and 45 years old). Cold-knife conization,
      LEEP, and both (conization and LEEP) were performed in 102 (51.3%), 95 (47.7%)
      and two (1%) women, respectively. Average ages were respectively, 33 +/- 7.3; 25
      +/- 6.73 and 30 +/- 2.8. RESULTS: Pregnancies occurred 2.6 and 4.8 years after
      LEEP and conization, respectively. Miscarriages and preterm pregnancies were more
      frequent in conization cases versus LEEP, 26% and 5.2%, 23% and 5.5%,
      respectively. CONCLUSION: If patients express a desire for pregnancy, LEEP should
      be the procedure of choice.

PMID- 19400412
TI  - The possible influence of increased body mass index on the clinical efficacy of
      standard human chorionic gonadotropin dosage.
AB  - OBJECTIVES: To evaluate whether the efficacy of standard (10,000 IU) hCG dosage
      is BMI dependent. PATIENTS & METHODS: During the study period, body mass index
      (BMI) was recorded in 261 consecutive women enrolled in our ICSI program. Women
      in the 90th BMI percentile were compared with those in the 10th percentile. The
      number and percent of mature metaphase-II (M-II) oocytes were considered as the
      outcome measure. RESULTS: Mean BMI of the 10th and 90th percentile groups were
      18.2 +/- 0.7 kg/m2 (n = 26) and 32.8 +/- 2.2 kg/m2 (n = 27), respectively. There
      were no differences between the groups in mean patients age, number of
      gonadotropin ampoules used, mean number of oocytes retrieved or the number and
      percentage of mature M-II oocytes. CONCLUSIONS: Standard (10,000 IU) hCG dosage
      is adequate to induce final oocyte maturation in IVF patients regardless of their
      BMI. This may imply that this hCG dosage is much higher than the dosage that is
      actually required.

PMID- 19400413
TI  - Serological testing for celiac disease in women with endometriosis. A pilot
      study.
AB  - PURPOSE OF INVESTIGATION: Celiac disease (CD) involves immunologically mediated
      intestinal damage with consequent micronutrient malabsorption and varied clinical
      manifestations, and there is a controversial association with infertility. The
      objective of the present study was to determine the presence of CD in a
      population of infertile women with endometriosis. METHODS: A total of 120 women
      with a diagnosis of endometriosis confirmed by laparoscopy (study group) and
      1,500 healthy female donors aged 18 to 45 years were tested for CD by the
      determination of IgA-transglutaminase antibody against human tissue
      transglutaminase (t-TGA) and anti-endomysium (anti-EMA) antibodies. RESULTS: Nine
      of the 120 women in the study group were anti-tTGA positive and five of them were
      also anti-EMA positive. Four of these five patients were submitted to intestinal
      biopsy which revealed CD in three cases (2.5% prevalence). The overall CD
      prevalence among the population control group was 1:136 women (0.66%).
      CONCLUSION: This is the first study reporting the prevalence of CD among women
      with endometriosis, showing that CD is common in this population group (2.5%) and
      may be clinically relevant.

PMID- 19400414
TI  - Microcolposcopy in the diagnostic evaluation of abnormal cervical cytology: when
      and why to do it.
AB  - Microcolposcopy is an in vivo cytological examination of the uterine cervix
      allowing the localization of exoendocervical precancerous lesions. The aim of
      this study was to assess the diagnostic reliability of microcolposcopy by means
      of correlation with histology, colposcopy and Pap test results. For the study,
      256 patients with abnormal Pap test results were selected and subjected to
      colposcopy and microcolposcopy with the aim of evaluating the presence of any
      intraepithelial lesions. One hundred and nine of these patients were subjected to
      a biopsy. Colposcopy, histology and cytology results were compared with those
      obtained by microcolposcopy. In low-grade squamous intraepithelial lesion (LSIL)
      cytology cases, the percentage agreement on lesion grade between Pap test and
      microcolposcopy results was 74%, while in high-grade squamous intraepithelial
      lesion (HSIL) cytology cases, it was equal to 80%. The comparison between
      colposcopy and microcolposcopy showed a level of agreement of 72% for lower
      grades and 68% for higher grades. Finally, histology was in agreement with
      microcolposcopy in 73% of cervical intraepithelial grade 1 neoplasia (CIN 1)
      cases and reached 71% for CIN 2-3. Microcolposcopy proved to be accurate with
      regard to the diagnosis of lesion grade, and showed to be definitive in patients
      where cytology was positive for HPV infection and colposcopy was not able to
      identify any lesions.

PMID- 19400415
TI  - The accuracy of frozen section analysis at hysterectomy in patients with atypical
      endometrial hyperplasia.
AB  - PURPOSE OF INVESTIGATION: To evaluate the accuracy of frozen section analysis in
      patients with atypical endometrial hyperplasia. METHODS: Women who underwent
      hysterectomy with frozen section analysis for atypical endometrial hyperplasia
      were identified. Frozen section evaluation aimed to give information about the
      presence of malignancy. Also, myometrial or cervical involvement was assessed in
      cases with malignancy to reveal the need for staging. Final pathological
      evaluation results were compared with intraoperative frozen section analyses.
      RESULTS: Twelve patients (34.3%) had endometrial cancer on final pathologic
      examination and eight required a staging procedure due to either myometrial
      invasion or cervical involvement; 75% of patients with endometrial cancer were
      successfully detected by frozen section analysis. Moreover, among women with
      cancer, frozen section examination revealed 75% of cases who required surgical
      staging. CONCLUSION: Frozen section analysis of hysterectomy specimens in
      patients with atypical endometrial hyperplasia is necessary to determine the
      presence of cancer and the need for surgical staging.

PMID- 19400416
TI  - Transvaginal sonography of cervical length and Bishop score as predictors of
      successful induction of term labor: the effect of parity.
AB  - OBJECTIVE: To evaluate the predictive value for successful labor induction of
      transvaginal ultrasound (TVS) of cervical length according to parity. METHOD: TVS
      of the cervix was performed before term labor induction. Induction was considered
      successful if vaginal delivery was achieved within 24 hours; 231 women were
      available for final analysis. RESULTS: Analysis of the receiver operator
      characteristics curve showed an optimal cut-off for cervical length of < or = 20
      mm for successful induction. Following multivariate logistic regression analysis,
      a sonographic short cervix (AOR 5.6; p < 0.001) was an independent predictor of
      successful induction but not a favorable Bishop score (p = 0.47). Among
      multiparas with a short cervix, positive and negative predictive values for
      successful induction were 98% (95% CI 90-100%) and 21% (95% CI 13%-32%) and among
      nulliparas, predictive values were 69% (95% CI 53%-82%) and 77% (95% CI 64%-87%)
      respectively. CONCLUSION: In nulliparas, cervical length can usefully predict
      labor induction outcome.

PMID- 19400418
TI  - Complete remission of OC-resistant catamenial shoulder joint pain and inguinal
      pain associated with extraperitoneal endometriosis following personalized GnRH
      agonist therapy.
AB  - BACKGROUND: Patients with severe extraperitoneal endometriosis require rapid
      remission and cannot wait for the effects of oral contraceptive hormones (OCs) to
      appear. CASE: We successfully achieved personalized gonadotropin-releasing
      hormone agonist (GnRHa) therapy for a patient with catamenial right shoulder
      joint pain and right inguinal pain associated with extraperitoneal endometriosis,
      which was completely unable to be suppressed by OCs. A total of 15 subcutaneous
      GnRHa depot injections over a period of 19 months was performed according to the
      serum estradiol and LH levels, in order to maintain long-term amenorrhea without
      any estrogen-deprivation effects. No recurrence of the catamenial symptoms has
      been observed for more than 35 months after the final GnRHa depot injection.
      CONCLUSION: Personalized GnRHa therapy should become the first-choice therapy for
      OC-resistant inoperable extraperitoneal endometriosis.

PMID- 19400417
TI  - Integrating cervical length measurement into routine antenatal screening and only
      emergency cerclage when indicated.
AB  - PURPOSE: To integrate cervical length measurement into antenatal screening and
      apply emergency cerclage when indicated to prevent spontaneous deliveries at < 34
      weeks of gestation. METHODS: Cervical length measurements of 400 pregnant
      volunteers were obtained at gestational weeks 12-14, 18-20 and 28-32. Whenever a
      cervical measurement < 30 mm was observed, vaginal cultures and bacterial
      vaginosis were investigated, and weekly cervical length measurements were
      performed thereafter. Emergency cerclage was performed whenever complete cervical
      effacement and > or = 3 cm cervical dilatation were observed before 32 completed
      weeks of gestation. We adopted and tested a strategy of only emergency cerclage
      application when clinically indicated after ultrasound screening and microbial
      monitoring of short cervices. Patients were given cyclooxygenase-inhibitors,
      progesterone, and antibiotics in the postoperative period. RESULTS: Spontaneous
      preterm births at < 34 weeks of gestation occurred in 15 women (3.8%). We
      performed five emergency cerclages according to the presented screening strategy
      between 20-28 weeks of gestation all of which reached > 34 weeks. We successfully
      postponed 62.5% (5/8) of deliveries before 32 completed weeks and 33.3% (5/15) of
      deliveries before 34 completed weeks. CONCLUSION: Routine cervical length
      measurement combined with serial transvaginal sonograms and vaginal microbial
      monitoring of the short cervices will avoid unnecessary prophylactic cerclages
      while increasing the success of emergency cerclages performed upon solid clinical
      findings.

PMID- 19400419
TI  - Near lethal endometriosis and a massive (64 kg) endometrioma: case report and
      review of the literature.
AB  - A 51-year-old morbidly obese, hypertensive, anemic, and amenorrheic female
      presented with anuria and respiratory symptoms. The patient had a distinctly
      massive abdomen with necrotic anterior abdominal wall, and laboratory findings
      revealed a leukocytosis, profound anemia, coagulopathy and renal failure. An
      abdominal sonogram showed a large, complex intra-abdominopelvic mass and ascites.
      At surgery, a massive, cystic left ovarian mass, 37 1 of ascitic/cyst fluid, and
      several peritoneal nodules were removed--a total of 64 kg of tumorous tissue.
      Histopathological evaluation of the mass revealed an endometrioma. We present
      this rare case of severe endometriosis in a morbidly obese patient who presented
      with an exceptionally large endometrioma (64 kg), multifactorial respiratory and
      renal failure, coagulopathy, and profound anemia.

PMID- 19400420
TI  - The development of placenta increta following pelvic transcatheter artery
      embolization for postpartum hemorrhage.
AB  - OBJECTIVE: Pelvic transcatheter artery embolization (TAE) has been widely used
      for the management of postpartum hemorrhage (PPH). However, the adverse effects
      of TAE on the subsequent pregnancy remain poorly understood. CASE: A 30-year-old
      woman, gravida 2, para 1, developed PPH due to atonic bleeding and underwent TAE.
      Thereafter, her menstrual cycle became irregular with less blood volume. Three
      years later, she became pregnant despite a thin endometrial thickness of 6 mm
      during the ovulatory period. She delivered a healthy baby at 39 weeks of
      gestation. No signs of placental separation were obtained, and an attempt at
      manual extraction of the placenta failed, followed by massive PPH. She underwent
      emergent TAE. The placenta was not spontaneously delivered even on day 8
      postpartum. A supracervical hysterectomy was performed due to a worsening
      intrauterine infection. Pathological examination revealed findings compatible
      with placenta increta. CONCLUSION: A TAE-associated thin endometrium may be
      attributable to the development of placenta increta. Pregnant women undergoing
      TAE should be managed carefully because the information about pregnancy outcomes
      after TAE remains scanty.

PMID- 19400421
TI  - Pregnancy-induced symptomatic pelvic and extra-pelvic cavernous hemangiomatosis.
AB  - BACKGROUND: Pregnancy-induced pelvic and extra-pelvic cavernous hemangiomatosis
      is a serious condition, associated with considerable maternal and fetal risks.
      This report describes the ultrasound (US) features and the clinical management of
      such rare condition in a young caucasian woman. CASE: A 20-year-old woman was
      referred to our department following the occurrence of swelling in her inguinal
      and vulvar area together with lipotimic episodes. Diffuse cavernous
      hemangiomatosis of the pregnant uterus associated with vaginal, inguinal and
      vulvar varicosities was diagnosed clinically and by 2D and 3D US. The patient
      underwent expectant management of the gestation, under close US monitoring of
      both superficial and inner varicosities, careful surveillance of the maternal and
      fetal condition and prophylaxis for thrombotic complications with medical
      therapy. A cesarean section was performed at 37 weeks of gestation because of the
      worsening of her lipotimic episodes and her unfavorable Bishop's score.
      CONCLUSION: This is the first report in which pregnancy-induced varicose disease
      involved contemporarily uterine, vaginal, inguinal, and vulvar veins totally
      sparing the lower extremities. This case suggests that, under close monitoring, a
      conservative approach can be adopted in such conditions. Vaginal delivery is to
      be preferred, but if cesarean section is required, the surgery should be
      performed under general anesthesia and packed red cells and plasma units should
      always be available.

PMID- 19400422
TI  - Serous cystadenoma with massive ovarian edema. A case report and review of the
      literature.
AB  - BACKGROUND: Massive ovarian edema is an usual tumour-like condition. It may be
      confused with an ovarian neoplasm. CASE: A 13-year-old female in premenarchy was
      referred as emergency case to a local hospital due to acute, severe and
      persistent hypogastric pain. She had noticed a gradual abdominal enlargement,
      mainly on the right abdomen during the last months. Ultrasound revealed a mass of
      a non-echogenic cystic compartment of 13 cm maximum diameter, and an area of
      mixed echogenicity of 11 cm maximum diameter at the anatomic site of the right
      ovary. The CA- 125 levels were increased. An unilateral salpingo-oophorectomy was
      performed. The pathology examination revealed serous cystadenoma with massive
      ovarian edema. CONCLUSIONS: Conservative treatment and ovarian suspension may be
      more appropriate, when histology on frozen section suggests a benign lesion.

PMID- 19400423
TI  - Acute urinary retention due to a uterine fibroid in a non-pregnant woman.
AB  - BACKGROUND: Uterine fibroids represent a rare cause of acute urinary retention
      (AUR) and most cases have been reported in pregnant women. CASE: We report the
      case of a non-pregnant woman who presented with AUR due to a uterine fibroid.
      CONCLUSION: When evaluating patients who present with severe oliguria or anuria,
      it is important to rule out urinary tract obstruction. Early identification of
      reversible causes of acute oliguria and institution of appropriate therapy are
      crucial to prevent the development of protracted acute renal failure. Close
      collaboration between gynaecologists, urologists and radiological services is
      required to promptly diagnose and treat uterine fibroid-associated AUR, a rare
      but reversible cause of acute renal failure.

PMID- 19400424
TI  - "Three cheers for retinal images"--a reply.

PMID- 19400425
TI  - On Frisby "three cheers for retinal images".

PMID- 19400426
TI  - Prior beliefs.

PMID- 19400427
TI  - The perceptual contrast of impossible shadow edges.
AB  - Luminance ratios along shadow edges remain the same even when they cross
      reflectance borders. According to Gilchrist (1988, Perception & Psychophysics 43
      415-424) this so-called ratio-invariance property is a crucial factor in the
      perception of shadows. However, Soranzo and Agostini (2004, Perception 33 1359
      1368) suggested that in some conditions (named 'impossible shadows'), a luminance
      pattern might still be perceived as a shadow even if the ratio-invariance
      property along its edge is violated. This can occur when an edge is collinear
      with another edge (contextual edge) which incorporates it, shares the same
      polarity, and generates a larger ratio. The hypothesis that impossible shadows
      are actually perceived as shadows is here tested by comparing the perceptual
      contrast of a luminance edge in the absence of a contextual edge (control
      condition) to that of both possible shadow edges (where the contextual and
      mediating edge share the same ratio) and impossible shadow edges (where the ratio
      of the contextual edge is larger rather than that at the mediating edge). We
      found that the perceived contrast of luminance edges shrinks in both possible and
      impossible shadow conditions rather than in the control condition. This evidence
      supports the hypothesis that a luminance pattern might be perceived as a shadow
      even when the ratio-invariance property is violated.

PMID- 19400428
TI  - The computation of shape orientation in search for Kanizsa figures.
AB  - Previous studies of visual search for illusory figures have provided equivocal
      results, with efficient search for Kanizsa squares (e.g., Davis and Driver, 1994
      Nature 371 291-293) contrasting with inefficient search for Kanizsa triangles
      (e.g., Grabowecky and Treisman, 1989 Investigative Ophthalmology and Visual
      Science 30 457). Here, we investigated whether shape orientation can explain
      these differences. The results from three experiments replicated previous
      findings: Kanizsa squares in experiment 1 could be detected more efficiently than
      Kanizsa triangles in experiment 2. In addition, when controlling for stimulus
      complexity in experiment 3, we found search for Kanizsa diamonds intermediate in
      efficiency. Taken together, these results suggest an oblique effect in search for
      Kanizsa figures with cardinal shape orientations leading to more efficient
      performance than oblique shape orientations. Our findings indicate that both
      shape orientation and stimulus complexity affect search for illusory figures.

PMID- 19400430
TI  - Grasping partly occluded objects: effects of global stimulus information on
      action.
AB  - We investigated here how partly occluded stimuli affect early and late prehension
      kinematics. Stimuli were pictures of partly occluded cylindrical objects with
      indentations or protrusions at regular intervals along the contour. They diverged
      into two plausible completions: a local completion, comprising a linear
      continuation of the contour, and a global completion, revealing a continuation of
      the contour indentations. Convergent stimuli with one plausible completion acted
      as controls. Twenty-eight participants repeatedly performed a grasping movement
      in darkness, as if they grasped the earlier-seen partly occluded cylinder. The
      peak acceleration of the hand opening (occurring at about 20% of the movement
      time) and the maximum hand aperture (at about 60% of the movement time) were
      taken to reflect the representation of the width of the stimuli used for action.
      The results show that the grasping movements were affected not only by local but
      also by global stimulus properties of which the representation remained stable
      over time.

PMID- 19400429
TI  - Normal susceptibility to visual illusions in abnormal development: evidence from
      Williams syndrome.
AB  - The perception of visual illusions is a powerful diagnostic of implicit
      integration of global information. Many illusions occur when length, size,
      orientation, or luminance are misjudged because neighboring visuospatial
      information cannot be ignored. We asked if people with Williams syndrome (WS), a
      rare genetic disorder that results in severely impaired global visuospatial
      construction abilities, are also susceptible to the context of visual illusions.
      Remarkably, we found that illusions influenced WS individuals to the same degree
      as normal adults, although size discrimination was somewhat impaired in WS. Our
      results are evidence that illusions are a consequence of the brain's bias to
      implicitly integrate visual information, even in a population known to have
      difficulty in explicitly representing spatial relationships among objects.
      Moreover, these results suggest that implicit and non-implicit integration of
      spatial information have different vulnerabilities in abnormal development.

PMID- 19400431
TI  - Spatial spread of interocular suppression is guided by stimulus configuration.
AB  - When the two eyes view dissimilar monocular stimuli, the resulting interocular
      suppression can spread beyond the region of explicit stimulus conflict: portions
      of one rival target will disappear even though there is no competing stimulation
      at the corresponding location in the other eye's view. In a series of experiments
      we examined whether this spread of suppression is spatially isotropic or governed
      by the configuration of the stimulus a portion of which is subject to
      suppression. Observers reported the incidence of stimulus disappearance at
      different locations along or nearby the contours of a large figure, part of which
      was suppressed by presentation of a continuous flash-suppression stimulus to a
      restricted region of the other eye. For all observers, suppression spread over
      several degrees along the contours of the figure, but tended not to spread to
      locations nearby but disconnected from the figure. Suppression spread effectively
      over a smoothly curved contour, and it spread around a sharp corner defined by
      two abutting contours, albeit less effectively. Suppression tended not to spread
      to features within the interior of a figure (a face), even if those features
      formed an integral part of the figure. A gap within a spatially extended stimulus
      arrested the spread of suppression, unless that gap appeared to arise from
      occlusion. Spread of suppression was unrelated to sensory eye dominance and was
      found with a more conventional binocular rivalry configuration, too. These
      findings implicate the involvement of neural circuitry in which inhibition
      propagates along paths of excitation beyond spatial regions of explicit
      interocular conflict.

PMID- 19400432
TI  - Race coding and the other-race effect in face recognition.
AB  - Other-race faces are generally recognised more poorly than own-race faces.
      According to Levin's influential race-coding hypothesis, this other-race
      recognition deficit results from spontaneous coding of race-specifying
      information, at the expense of individuating information, in other-race faces.
      Therefore, requiring participants to code race-specifying information for all
      faces should eliminate the other-race effect by reducing recognition of own-race
      faces to the level of other-race faces. We tested this prediction in two
      experiments. Race coding was induced by requiring participants to rate study
      faces on race typicality (experiment 1) or to categorise them by race (experiment
      2). Neither manipulation reduced the other-race effect, providing no support for
      the race-coding hypothesis. Instead, race-coding instructions marginally
      increased the other-race effect in experiment 1 and had no effect in experiment
      2. These results do not support the race-coding hypothesis. Surprisingly, a
      control task of rating the attractiveness of study faces increased the other-race
      effect, indicating that deeper encoding of faces does not necessarily reduce the
      effect (experiment 1). Finally, the normally robust other-race effect was absent
      when participants were instructed to individuate other-race faces (experiment 2).
      We suggest that poorer recognition of other-race faces may reflect reduced
      perceptual expertise with such faces and perhaps reduced motivation to
      individuate them.

PMID- 19400433
TI  - What is meant by impaired configural processing in acquired prosopagnosia?
AB  - Apperceptive prosopagnosia is supposedly characterised by impaired configural
      processing, which could refer to either perception of spatial structure or
      holistic mechanisms. Ten prosopagnosic patients were tested with (i) dot
      patterns, to determine if manipulations of complexity, size, orientation, or the
      regularity of global structure generated effects consistent with the holistic
      hypothesis; and (ii) hierarchical letters, to probe for a global 'whole-object'
      processing deficit. With dot patterns (experiment 1) patients were impaired even
      for simple two-dot stimuli, but did better with more complex patterns, when size
      or orientation varied, or with a regular global structure. In experiment 2, they
      demonstrated normal latency effects of global-level processing. Apperceptive
      prosopagnosia, including that from lesions encompassing the right fusiform gyrus,
      is thus associated with a 'configural deficit' that impairs perception of spatial
      structure, not just for faces but also for non-facial patterns. While it cannot
      be concluded that holistic processing is entirely normal in these subjects, their
      performance shows significant modulation by whole-object structure, indicating
      that some whole-object processing is occurring in these patients.

PMID- 19400434
TI  - Perceptual memory for highly familiar people's body shape: manipulation of images
      of the self and friend.
AB  - Previous studies have shown that people's ability to detect, from memory,
      alterations in highly familiar faces is excellent. Indeed, just noticeable
      differences for the detection of small alterations in a recognition-memory task
      were not significantly different from the corresponding measures in a perceptual
      discrimination task (Bredart and Devue, 2006 Perception 35 101-106; Ge et al,
      2003 Perception 32 601-614). The object of the present study was to evaluate
      whether people's perceptual memory for body shapes of very familiar persons
      reaches the high level of precision that was reported for face memory. For one
      group of participants, the task was to detect body shape alterations (an increase
      or a decrease of 2% to 10% of the waist-to-hip ratio) on photographs depicting
      either themselves or a friend. For another group of participants who did not know
      the target persons, the task was to discriminate whether two photographs
      presented side by side were the same or not. Results showed that the detection of
      alterations was significantly better in the perceptual-discrimination task than
      in the recognition-memory tasks (for the participant's own body as well as for
      the friend's body). In conclusion, the high fidelity of perceptual memory for
      very familiar faces does not extend to familiar body shapes.

PMID- 19400435
TI  - Movement and the rubber hand illusion.
AB  - When a participant views a rubber hand being stroked by a paintbrush while
      his/her real hand is unseen and similarly stroked by another paintbrush, a
      misperception known as the rubber hand illusion occurs whereby tactile sensations
      are falsely referred to the non-body part. The purpose of the current study was
      to further examine the rubber hand illusion with conditions of movement. An
      apparatus was devised that would synchronise visual with felt movement in an
      active condition and a passive condition. An asynchronous condition was included
      as a control in which visual and felt movement were purposely disconnected. The
      three movement conditions (active, passive, and asynchronous) were statistically
      compared in order to assess our prediction that synchronous conditions of
      movement (especially active) would generate more reports of the illusion. The
      performance of the movement conditions was evaluated against a visual-tactile
      condition, which is a known contributor to the rubber hand illusion. Not only
      significantly more robust reports of the illusion were obtained when visual
      movement and felt movement were synchronised but there was also a trend toward
      stronger reports in the active condition rather than the passive condition.
      Interestingly, the pattern of results differed according to the particular
      question on the self-report.

PMID- 19400436
TI  - Perceived self-tilt in dynamic visual stimuli: evidence for suppression by
      vestibulo-tactile inputs.
AB  - Perception of self-tilt is affected by shearing force acting on the otolith
      organs in the ears, by pressure acting on the tactile receptors in the skin, and
      by visual pattern falling on the retinae. We examined how the vestibular,
      somatosensory, and visual inputs interact in judging self-tilt in roll. Each of
      fourteen observers, sitting in a chair and gazing at a rotation pattern in the
      frontal plane, was tilted to various angles and verbally judged to what extent
      his/her body was tilted. The independent variables examined were body tilt (0
      degrees to +/- 108 degrees), and the rate (7.5 degrees s(-1), 15 degrees s(-1),
      and 30 degrees s(-1)) and direction (CW and CCW) of the visual rotating pattern.
      We found that (i) the sensory scale for self-tilt is represented by a third-order
      polynomial lacking the quadratic component, (ii) perceived self-tilt for the CW
      (or CCW) rotation of the visual pattern is displaced CCW (or CW), (iii) the
      linear and cubic components of the equation increase with an increase in the rate
      of rotation of the visual pattern, and (iv) if the body is tilted in concord with
      the direction of vection, the velocity of visual pattern is effective, but when
      the body is tilted in conflict with the direction of vection, it is less
      effective. These findings are interpreted in terms of vestibular and
      somatosensory suppressions exerted on the effects of vection.

PMID- 19400437
TI  - Graded structure in odour categories: a cross-cultural case study.
AB  - The existence of graded structure in fruit and flower odour categories and its
      stability in different cultures is examined. Groups of students from France, the
      United States, and Vietnam performed a typicality rating task, a similarity
      judgment task, a membership verification task, a recognition memory task, a
      familiarity rating task, and a free identification task using a set of 40
      odorants (20 fruit odorants and 20 flower odorants). Overall, our results
      demonstrate that fruit and flower odour categories possess graded structure.
      Moreover, principal component analyses of the data revealed the implication of
      typicality in a variety of cognitive tasks where typical odours receive a
      preferential processing compared to atypical ones. Finally, our results suggest
      that typicality can be predicted to a certain extent by experiential knowledge
      but that other determinants play a role in odour category structure. Altogether,
      this study confirms that graded structure is a universal property of categories
      and suggests that universals and cultural specifics can both constrain the
      emergence of odour category structures.

PMID- 19400438
TI  - How many arms make a pair? Perceptual illusion of having an additional limb.
AB  - What are the natural constraints for the human body representation? Here I report
      a perceptual illusion where healthy individuals experience having two right arms,
      with both sensing touches applied to them. This effect reveals how visual and
      tactile signals from the body are integrated in a probabilistic fashion,
      resulting in a single limb being represented at two locations at the same time,
      giving rise to a perceptual duplication of this limb. This is an important
      observation because it suggests that even the gross morphology that we experience
      of ourselves is a construct resulting from dynamic and integrative processes in
      the perceptual systems.

PMID- 19400439
TI  - Scotopic foveal afterimages.
AB  - If, after being in the dark for many minutes, one views an extended surface under
      dim (scotopic) illumination, one fails to see any hint of the dark spot at the
      center of gaze that might be expected from the absence of rods in the fovea. Here
      we report that, if the surface is suddenly completely darkened, one sees for a
      few seconds a relatively bright spot, about 2 deg in size, at the point of
      fixation. If the surface is now restored to its original brightness, a dark spot
      of similar size appears where one fixates, that again lasts for several seconds.
      All this can be observed with no elaborate apparatus.

PMID- 19400440
TI  - [We only indicate extracorporeal circulation when the thrombus is situated in
      part of the right atrium and is introduced in the right ventricle, in which case
      its use is reduced to a very small proportion of patients].

PMID- 19400441
TI  - [Surgical treatment of renal tumours with venous extension].
AB  - OBJECTIVES: Renal carcinoma accounts for 3% of malignant urological tumors. The
      existence of tumor thrombus in the venous system is more infrequent, and, despite
      it was believed until recently its presence worsened the diagnosis of the
      disease, currently it is accepted that in the absence of metastatic or lymph node
      disease, surgery is the treatment of choice and potentially curative for these
      tumors. METHODS: Between June 2003 and November 2007 eight patients with renal
      disease and venous thrombus underwent surgery; two of them wereT3c and six T3b;
      in five of them surgery was carried out in association with the heart surgery
      team in our centre. Three of them underwent surgery with extracorporeal
      circulation. Mean patient age was 56 years. RESULTS: Tumor thrombus was grade I
      in one patient, grade II in 4 patients, grade III in one patient, and grade IV in
      two patients. In all patients with tumor grade > or = III, as well as two with
      grade II, surgery was performed in conjunction with the department of heart
      surgery. The operation with extracorporeal circulation, deep hypothermia,
      cardioplegia, and antegrade and retrograde brain perfusion was performed in
      grades III and IV. Midline incision was performed, with or without sternotomy,
      depending on the level of the thrombus. Hemorrhage was the most frequent
      perioperative complication. DISCUSSION: It is essential to know the exact level
      of the cephalic extreme of the tumor thrombus to design the proper surgical
      strategy; for that, we can use MRI, CT scan or ultrasound. Therefore, surgical
      approach, multidisciplinary cooperation and use of extracorporeal circulation
      will depend on such extension of the thrombus and concurrent factors of the
      patient. A good surgical strategy, as well as early surgery may avoid the use of
      venous filters preoperatively. CONCLUSIONS: Venous wall invasion seems to be
      related with a greater incidence of lymph node disease, but these patients are
      candidates to intention-to-cure radical surgery. Thrombus level is not a
      prognostic factor per se, but it should be taken into consideration for surgical
      planning. After radical surgery survival rates achieved are similar to those of
      tumors without venous thrombus.

PMID- 19400443
TI  - [Impact of surgical treatment of female stress urinary incontinence on the
      quality of life of patients].
AB  - OBJECTIVES: To evaluate the quality of life of patients with stress urinary
      incontinence (SUI) operated in the Department of Urology at the Complejo
      Hospitalario Universitario in Albacete (CHUA). METHODS: Between November 2001 and
      December 2005, 126 patients with SUI have completed a questionnaire in our
      centre, before and after undergoing surgery with sling techniques. The
      questionnaire was the King's Health Questionnaire (KHQ), which is a specific
      instrument for the measurement of quality of life in patients with urinary
      incontinence. RESULTS: Mean patient's age was 57.09 years (DE: 9.57). Twelve
      women (9.5%) had history of previous urinary incontinence surgery. Mean urinary
      incontinence evolution time was 114.48 months, with a median of 96 months. 38
      patients (30.2%) did not present cystocele, 61 (48.4%) presented grade III
      cystocele, 25 (19.8%) grade II, and 2 (1.6%) grade I. Before surgery, the scale
      with best score was Personal relationships, with a mean score of 26.8, whereas
      the scale with worst scores was Impact of urinary incontinence, with a mean score
      of 82.96. All operations performed consisted in various techniques of
      transvaginal slings, except one case (0.8%) in which the Kelly technique was
      performed. Impact of urinary incontinence was the scale with a greater number of
      patients improving after surgery; 82.9% of the patients (101 cases) gave a better
      score. The scales showing greater differences of the mean value comparing
      before/after surgery were impact of urinary incontinence, limitation on the daily
      life activity, and limitation on social activity. Personal relationships and
      General health were the two with the smallest improvements. CONCLUSIONS: Surgery
      demonstrated to improve the symptoms secondary to this disease, therefore, it
      results in an improvement of the quality of life that is evident in all scales of
      the questionnaire, mainly in the impact of urinary incontinence, limitations on
      physical activity, limitations on daily life, and limitation on social activity
      scales.

PMID- 19400442
TI  - [Survival of patients with advanced renal carcinoma treated with interferon].
AB  - OBJECTIVES: To determine survival of patients with metastatic renal carcinoma
      treated with interferon. METHODS: Retrospective longitudinal study with 18
      patients with the diagnosis of metastatic renal carcinoma treated in the
      University Hospital Manuel Fajardo between July 2002 and September 2007 with
      radical surgery and alpha 2b recombinant interferon, either adjuvant or as
      monotherapy. RESULTS: 74% (14/18) of the patients were males, 26% (5/18) females.
      72% (13/18) underwent radical surgery plus interferon, and 28% (5/18) received
      interferon monotherapy. Complete response was observed in 22% (4/18); 78% (14/18)
      had progression. One, 2, 4 and 5-year survivals were 50%, 33%, 28%, and 22%,
      respectively. CONCLUSIONS: No significant response was found. There was not tumor
      regression in any case using interferon. Survival was better in cases undergoing
      radical nephrectomy plus interferon than cases treated with interferon
      monotherapy.

PMID- 19400444
TI  - [Urachus cystopexy: new technique for bladder suspension associated to the
      Burch's technique in the treatment of cystocele and stress urinary incontinence.
      Long-term follow-up].
AB  - OBJECTIVES: To compare long term efficacy and morbidity in patients with stress
      urinary incontinence treated using Burch's colpopexy versus Burch's colpopexy
      plus urachus-cystopexy. METHODS: Retrospective, longitudinal comparative,
      observational study in 129 patients with stress urinary incontinence (SUI) or
      mixed urinary incontinence (MUI). Fifty four patients underwent Burch's colpopexy
      (group B) and 75 patients underwent Burch's colpopexy and urachus-cystopexy
      (group B U). These patients completed inclusion criteria from January 1994 to
      March 2005. The severity of SUI was evaluated by means of the number of pads used
      in 24 hours. Cure was defined as patients not using any pad for urinary leakage;
      improvement, when the number of pads used decreased to one pad a day; and failure
      when the patients used more than 1 pad in 24 hours. In MUI the urge urinary
      incontinence (UUI) component was evaluated separately. RESULTS: After 12 months
      of follow-up, 47 patients of group B and 67 patients of group BU were evaluated
      analyzing cure/improvement. Either one were observed in 74.4% (29/6) and 97%
      (58/7) respectively (p = 0.001). At 24 months follow up, in 35 patients of group
      B and 42 of group BU, a rate of 65.7% (22/3) and 97.6% (37/4) was observed
      respectively (p = 0.014). MUI was present in 53.7% of group B and 58.6% patients
      of group BU. An independent analysis was made on urge urinary incontinence (UUI)
      in these patients at 12 months; 53.1% of group B and 19.4% of group BU had UUI (p
      = 0.000). At 24 months, 50% of patients of group B and 26.19% of group BU had UUI
      (p = 0.029). De novo UUI was present in 19.4% of group B and 5.97% of group BU (p
      = 0.000) at 12 months follow-up, and in 17.64% of patients of group B and 13.95%
      of group BU (p = 0.005) at 24 months. Complications related to urachus-cystopexy
      presented trans-operatively: vesical injury in 3 of the initial cases, solved
      with bladder closure in two layers and vesical catheter for 7 days approximately.
      CONCLUSIONS: Burch's procedure in addition to urachus-cystopexy was better for
      the treatment of SUI and UUI than Burch's procedure alone in a long term clinical
      follow-up. Surgical fixation of the urachus to the anterior abdominal wall
      provides extra support to the bladder and probably reduces its displacement
      during strength, avoiding tension of urethral and bladder neck fixations and
      increasing the efficacy of Burch's procedure.

PMID- 19400445
TI  - [Percutaneous treatment of calyceal diverticulum associated with lithiasis].
AB  - OBJECTIVES: To report the case of a 47-years-old woman with several small stones
      located inside a calyceal diverticulum of the right kidney and to highlight the
      importance of minimally invasive endourological treatment in these cases.
      METHODS: Owing to the presence of diverticular calculi and clinical symptoms of
      recurrent infection, we decided to perform percutaneous nephrolithotomy (PNL).
      After Holmium-YAG laser calculi fragmentation and removal of all stone material,
      we fulgurated the diverticular lining and infundibulum with a resectoscope and a
      rollerball electrode. RESULTS: The patient is free of symptoms after 6 months
      follow-up. The disappearance of the calculi and diverticulum is confirmed with
      excretory urogram. CONCLUSIONS: Endourological approach for diverticular calculi,
      such as percutaneous nephrolithotomy (PNL), is a minimally invasive treatment
      with excellent results and low morbidity. Using this procedure we are able to
      perform stone removal and cavity fulguration. According to this, we think that
      endourological techniques, and specially PNL could be the first option for
      treatment in selected cases of this pathology.

PMID- 19400446
TI  - [Nephron-sparing surgery for the treatment of small renal tumors. The role of
      radiofrequency].
AB  - OBJECTIVES: Laparoscopically assisted radiofrequency is a minimally invasive
      nephron-sparing treatment option for renal tumors, mainly in patients with high
      comorbidity. We present the short-term results of our series patients treated
      with this novel technique. METHODS: Renal lesions smaller than 4 cm, suspicious
      of malignancy or metastasis on CT scan or MRI are candidates for radiofrequency.
      Under laparoscopic vision the tumor is identified, and percutaneous biopsy is
      performed. Depending on the size of the tumor, a number of punctures with the
      radiofrequency needle are performed with the aim to achieve tumor necrosis during
      at least one cycle of radiofrequency. Follow-up is performed with MRI in the
      first postoperative day and then after CT scan or MRI at 1, 3, 6 and 12 months.
      The persistent absence of contrast or vascular necrosis of the lesion is
      considered a satisfactory ablation without recurrence. RESULTS: 12 patients, two
      with metastasis and ten with primary lesions (mean age 60.8 years), with one or
      more lesions suspicious of malignancy underwent radiofrequency. Mean ASA was 2.4.
      15 tumors were treated, with a mean diameter of 2.8 cm. An average of 2.5
      punctures was performed with the radiofrequency needle. Biopsy results showed:
      one case of thyroid cancer metastasis, one case of melanoma metastasis, and 10
      cases of renal cell carcinoma. Mean hospital stay was 25.8 hours. There were not
      short-term complications. Follow-up time was 8.8 months. Today there is no
      evidence of recurrence in imaging tests. CONCLUSIONS: Radiofrequency is effective
      eradicating small renal lesions, both primary and metastatic; it is especially
      useful in patients with high comorbidity. Despite the number of patients with
      adequate follow-up is not enough, the technology is promising. The approach under
      laparoscopic vision contributes to an effective biopsy, avoiding dissemination
      and enabling a more precise radiofrequency by direct vision control of tumor
      necrosis.

PMID- 19400447
TI  - [Closure of a neobladder-vaginal fistula in a patient with Studer's type
      neobladder using a transvaginal approach with interposition of a Martius' flap].
AB  - OBJECTIVE: We report a case of neobladder-vaginal fistula in a patient, and its
      closure using a Martius flap interposition. METHODS: A 51-year-old patient
      required cystectomy and Studer's neobladder for invasive bladder adenocarcinoma.
      After urethral catheter removal she presented constant leakage and was diagnosed
      by cystoscopy of neobladder-vaginal fistula. RESULTS: This complication was
      successfully treated using a vaginal approach with closure in two layers and
      interposition of a Martius flap. CONCLUSIONS: Neobladder is a rare indication in
      women, as it is the eventuality of presenting this type of fistula. The adequate
      approach to treat it is still controversial. In our experience and after
      reviewing literature we think vaginal closure using a Martius flap interposition
      is a good technique to treat a neobladder-vaginal fistula.

PMID- 19400448
TI  - [Polyorchidism].
AB  - OBJECTIVE: To report one case of supernumerary testicle, a rare entity with
      around 100 cases published. METHODS: 44-year-old male patient consulting for
      incidental discovering of a right scrotal mass. The diagnosis of polyorchidism
      was suspected after physical examination, ultrasound, and CT scan, and confirmed
      subsequently on surgical exploration and biopsy. Due to the absence of pathology
      and complete normal seminal lines decision was taken to not perform orchiectomy
      of the supernumerary testicle. RESULTS: There are classifications for proper
      evaluation of polyorchidism, which state the relation between site of the
      testicle in relation to scrotum, existence or absence of independent epididymis
      and vasa deferentia for both testicles. CONCLUSIONS: Although remotely, there is
      a possibility of malignant degeneration of these testicles, so that surgical
      exploration and excision of the supernumerary testicles when their biopsy is
      doubtful in terms of dysplasia or if they present carcinoma in situ or they are a
      source of pain.

PMID- 19400450
TI  - [Frontal mass simulating lipoma as a clinical presentation of prostatic
      adenocarcinoma].
AB  - OBJECTIVE: To report one case of metastatic prostatic carcinoma with a gaudy
      presentation as a lump which resulted to be a cutaneous metastasis. METHODS: We
      describe the debut in a patient, who thanks to the pathologic analysis of a
      lesion mimicking a lipoma, which was reported as adenocarcinoma, was worked up
      for prostatic adenocarcinoma and diagnosis was reached. We performed a
      bibliographic review using an electronic bibliographic search in PubMed (MEDLINE)
      using the terms "Prostatic Neoplasm" (MesH) AND "Neoplasm Metastasis" (MesH) AND
      "cutaneous" (free text). Most publications are case reports reviewing the
      probable dissemination way and localization. RESULTS: Positive
      immunohistochemical staining for PSA confirmed the origin of the metastasis,
      although PSA value did not offer doubts due to its value over 1100 ng/ml.
      Regarding the bibliographic search we obtained more than 26 papers, and selected
      only 8 that were adjusted to the objectives of our work. Cutaneous metastasis of
      prostatic origin appear in less than 0.3% of the cases, because bone, lymph node,
      and visceral disease are more frequent. Cases appearing during the evolution of
      the disease and metastasis after laparoscopic procedures are described.
      CONCLUSIONS: Cutaneous metastases of prostatic adenocarcinoma are very rare, but
      even rarer is it being the debut of the disease.

PMID- 19400449
TI  - [Multilocular cystic nephroma. Report of three new cases].
AB  - OBJECTIVE: To analyze the presentation of multilocular cystic nephroma and its
      diagnostic-therapy scheme. METHODS: We report the three last new cases presenting
      in our department in a period of three years. RESULTS: Multilocular cystic
      nephroma is a benign lesion, rare that appears both in adult age, generally
      asymptomatic, and in children, frequently as a palpable mass. Differential
      diagnosis with malignant tumours is required. CONCLUSIONS: The great variety of
      clinical presentations, differential diagnosis and places of origin of the cases
      is demonstrated, being this a reflection of our daily medical practice, in which
      we cannot reach definitive diagnosis with imaging tests, being the Bosniak's
      classification very useful for the setting of indication for surgery, which will
      give definitive diagnosis of multilocular cystic nephroma or what is more
      important will rule out malignancy.

PMID- 19400451
TI  - [Spermatic cord leiomyosarcoma. Case report and bibliographic review].
AB  - OBJECTIVE: To report one new case of paratesticular leiomyosarcoma. METHODS: We
      describe the case of a 68-year-old male patient consulting for right groin pain
      over two years with a physical examination corresponding to right inguinal
      hernia. During surgery for hernia correction a paratesticular mass was
      discovered. RESULTS: Right radical orchiectomy was performed. After the operation
      there was a recurrence at the scar which was operated and finally the disease
      progressed both locally and systemically. CONCLUSIONS: We point out the scarce
      frequency of this type of tumours. We believe that orchiectomy and excision of
      the cord is the treatment of choice. The use of adjuvant therapies doesn't
      influence survival significantly.

PMID- 19400452
TI  - [Diagnostic and therapeutic management of renal hydatidosis].
AB  - OBJECTIVE: Renal hydatidosis is caused by Echinococcus granulosus and is
      extremely rare, accounting for 3-4% of the cases of hydatidosis, being the third
      site after liver and lungs. It generally remains asymptomatic for years and the
      most frequent symptoms are pain, feeling of flank heaviness, and dysuria. In
      front of a compatible clinical picture, we studied the diagnostic, therapeutic,
      and follow-up schemes reviewing the literature. METHODS: We performed an
      electronic bibliographic search in PubMed (MEDLINE) which MESH terms
      "Echinococcosis" [MeSH] AND "urinary tract" [MeSH] and bibliographic citations.
      We perform a review on epidemiology, vital cycle of the parasite and management
      of patients with hydatidosis. Most published papers correspond to case reports
      from different localisations, although we found some reviews. RESULTS: We found a
      total of 137 papers, we selected 23 of them because they were related; five were
      reviews, but we only include 10 of them in our references. Although most were
      case reports, the reviews analyse the cycle of the Echinococcus and its various
      host sites (organs) in the human host. The human being may become an intermediary
      host through contact with the definitive host (dogs) or by taking contaminated
      water or vegetables. CONCLUSIONS: Thanks to the combination of history, imaging
      tests and serology we get close to the diagnosis in up to 80%. In many cases
      conservative surgery is possible, but after suspicion we should always sterilise
      with albendazole before surgical treatment, and monitor serum titles of anti
      Echinococcus antibodies.

PMID- 19400453
TI  - [Ocular proptosis in a patient with prostatic adenocarcinoma].
AB  - OBJECTIVE: To reach information on a rare clinical finding secondary to on
      infrequent location of tumour dissemination in prostatic cancer. METHODS: We
      present a case of an adult male with ocular left proptosis and history of
      prostatic cancer. CONCLUSIONS: In adults males, the prostatic cancer should be
      born in mind in the differential diagnosis of the masses in orbital location.

PMID- 19400454
TI  - [Severe renal trauma].

PMID- 19400455
TI  - [Spermatic cord duplication].

PMID- 19400456
TI  - [Giant intra scrotal lipoma].

PMID- 19400457
TI  - [Comments on the article "Renal hematomas following extracorporeal lithotripsy in
      324 sessions...," published in Arch. Esp. Urol. 2008; 61 (8): 889-914].

PMID- 19400458
TI  - Comparison of clinical, radiographic, computed tomographic, and magnetic
      resonance imaging methods for early prediction of canine hip laxity and
      dysplasia.
AB  - The purpose of the study was to use two palpation methods (Bardens and Ortolani),
      a radiographic distraction view, three computed tomography (CT) measurements
      (dorsolateral subluxation score, the lateral center-edge angle, and acetabular
      ventroversion angle) and two magnetic resonance (MR) imaging hip studies
      (synovial fluid and acetabular depth indices) in the early monitoring of hip
      morphology and laxity in 7-9 week old puppies; and in a follow-up study to
      compare their accuracy in predicting later hip laxity and dysplasia. The MR
      imaging study was performed with the dog in dorsal recumbency and the CT study
      with the animal in a weight-bearing position. There was no association between
      clinical laxity with later hip laxity or dysplasia. The dorsolateral subluxation
      score and the lateral center-edge angle were characterized by a weak negative
      correlation with later radiographic passive hip laxity (-0.26 < r < -0.38, P <
      0.05) but its association with hip dysplasia was not significant. There was an
      association between early radiographic passive hip laxity and synovial fluid
      index with later passive hip laxity (0.41 < r < 0.55, P < 0.05) and this was
      significantly different in dysplastic vs. nondysplastic hips (P < 0.05). There
      was no association between the remaining variables and later hip laxity or
      dysplasia. The overlapping ranges of early passive hip laxity and synovial fluid
      index for hip dysplasia grades and the moderate correlations with the later
      passive hip laxity make the results of these variables unreliable for use in
      predicting hip laxity and dysplasia susceptibility.

PMID- 19400459
TI  - Computed tomographic arthrography of the stifle for detection of cranial and
      caudal cruciate ligament and meniscal tears in dogs.
AB  - The purpose of this study was to evaluate the utility of single-detector computed
      tomographic arthrography (CT arthrography) for the diagnosis of cranial and
      caudal cruciate ligament and meniscal lesions in the dog stifle. Four normal and
      25 abnormal stifle joints, determined to have lesions related to intra-articular
      ligamentous insufficiency based on clinical history, orthopedic examination, and
      survey orthogonal radiographs, were imaged using a previously developed CT
      arthrography protocol. Surgery was performed immediately following the CT
      procedure. Three board-certified radiologists inexperienced at interpreting CT
      stifle arthrograms reviewed all CT studies independently, and then as a group,
      without knowledge of surgical or necropsy findings. Sensitivity, specificity,
      positive predictive value, and negative predictive value for determination of
      cranial and caudal cruciate and meniscal tears were calculated for each
      individual reviewer and based on group consensus. All reviewers identified the
      normal canine stifle joints imaged correctly. Reviewers did well in
      discriminating normal from torn cranial cruciate ligaments, with sensitivities of
      96-100% and specificities of 75-100%. No reviewer correctly identified the
      solitary caudal cruciate ligament tear and specificity ranged from 89.3% to 100%.
      Reviewers were less adept at discriminating normal from torn meniscal
      fibrocartilage, with sensitivities of 13.3-73.3% and specificities of 57.1-100%.
      Interpretive accuracy improved slightly when consensus scores were compared with
      surgical findings. Single-detector CT arthrography may be useful for identifying
      pathology of the canine cruciate ligaments but is of limited value for assessing
      the menisci.

PMID- 19400460
TI  - The computed tomographic appearance of equine temporohyoid osteoarthropathy.
AB  - Equine temporohyoid osteoarthropathy is characterized by progressive osseous
      proliferation of the temporohyoid articulation and surrounding structures. The
      diagnosis has generally been made using radiography and endoscopy of the guttural
      pouch. Recently, computed tomography (CT) has been used in the diagnosis of
      temporohyoid osteoarthropathy. This study was performed to determine the CT
      imaging characteristics of temporohyoid osteoarthropathy and to compare these to
      radiographic and endoscopic findings. CT scans from 16 horses with a final
      diagnosis of temporohyoid osteoarthropathy were reviewed. Five horses that had
      undergone CT scan for reasons other than temporohyoid osteoarthropathy were
      included as controls. Qualitative and quantitative data were used to describe the
      magnitude of the CT findings. Osseous proliferation of the stylohyoid bone and
      temporohyoid articulation was found to be a consistent feature of temporohyoid
      osteoarthropathy. Thickening of the ceratohyoid bone and proliferation of its
      articulation with the stylohyoid bone was frequently identified and this finding
      may have surgical implications. Horses with neurologic deficits had increased
      stylohyoid width that was significantly different than the subclinically affected
      side. CT evaluation also allowed the identification of subclinical bilateral
      disease in horses thought to be unilaterally affected based on clinical
      examination.

PMID- 19400461
TI  - Puppy line, metaphyseal sclerosis, and caudolateral curvilinear and
      circumferential femoral head osteophytes in early detection of canine hip
      dysplasia.
AB  - Ventrodorsal extended hip radiographs were analyzed from Foxhounds, Irish
      setters, Greyhounds, and Labrador retrievers radiographed four to seven times
      between 8 and 110 weeks of age. Occurrence in these 91 dogs of a puppy line, an
      ill-defined zone of proximal femoral metaphyseal sclerosis, a femoral neck linear
      sclerosis, or circumferential linear femoral head osteophytosis at 15-17 weeks of
      age were compared with hip joint laxity, as measured by distraction index, and to
      later findings of caudal curvilinear femoral neck osteophytes, circumferential
      femoral head osteophytes, hip incongruity consistent with hip dysplasia and
      degenerative joint disease by 52 weeks of age. A puppy line and/or femoral
      metaphyseal sclerosis was common at 15-17 weeks of age for dogs at mimimal risk
      (Greyhounds) and high risk (Foxhounds) of developing early degenerative joint
      disease associated with canine hip dysplasia. Though 44% of Greyhound hips had
      puppy lines and 28% had femoral metaphyseal sclerosis at 15-17 weeks of age, no
      Greyhound had a caudolateral curvilinear osteophyte or circumferential femoral
      head osteophyte at 24-27 or 52 weeks of age. No significant relationship was
      found between occurrence of a puppy line, a circumferential femoral head
      osteophyte or femoral metaphyseal sclerosis at 15-17 weeks and canine hip
      dysplasia or degenerative joint disease incidence at 42-52 weeks. Presence of a
      caudolateral curvilinear osteophyte in at least one hip at 24-27 weeks was
      significantly related to the diagnosis of canine hip dysplasia by 42-52 weeks.
      When both a caudolateral curvilinear osteophyte and a circumferential femoral
      head osteophyte were present in a hip at 24-27 weeks, degenerative joint disease
      was evident in all such hips by 42-52 weeks of age.

PMID- 19400462
TI  - Relationship between prostatomegaly, prostatic mineralization, and cytologic
      diagnosis.
AB  - Canine prostatic disease is commonly evaluated with abdominal ultrasound and
      radiographs. Mineralization of the prostate is often reported, but the clinical
      relevance of this finding is currently not known. The-purpose of this study was
      to characterize the relationship between ultrasonographic and radiographic
      prostate mineralization and the final diagnosis. Medical records of 55 dogs with
      evidence of prostatomegaly or prostatic mineralization and a cytologic diagnosis
      were evaluated. Radiographs and ultrasound images were assessed for caudal
      retroperitoneal lymphadenopathy, vertebral lesions, or other signs of metastasis,
      and mineralization was assessed semiquantitatively. Twenty-two of 55 (40%) dogs
      had prostatic neoplasia. Regarding neoplasia, mineralization in neutered dogs had
      a positive predictive value (PPV) of 100%, a negative predictive value (NPV) of
      50%, and a sensitivity and specificity of 84% and 100%, respectively.
      Mineralization in intact dogs had a PPV of 22%, an NPV of 96%, and a sensitivity
      and specificity of 67% and 77%, respectively. All neutered dogs with
      prostatomegaly but not prostatic neoplasia had bacterial prostatitis and were
      castrated within the previous 3 months. Intact dogs with prostatomegaly and
      mineralization but not neoplasia had paraprostatic cysts (n = 3), benign
      prostatic hyperplasia (n = 2) or prostatitis (n = 2). Mineralization score was
      not indicative of neoplasia. In conclusion, neutered dogs with prostatic
      mineralization were very likely to have prostatic neoplasia. Intact dogs were
      unlikely to have prostatic neoplasia if no mineralization was found on
      radiographs or ultrasound.

PMID- 19400464
TI  - MR imaging of histiocytic sarcoma of the canine brain.
AB  - Histiocytic sarcomas are characterized by proliferation and/or infiltration of
      neoplastic histiocytes localized to specific organs, unlike malignant
      histiocytosis which involves many organ systems. Only a few cranial histiocytic
      sarcomas have been reported. Here we describe four dogs that presented with
      neurological deficits referable to the forebrain, and were diagnosed
      histologically as having histiocytic sarcoma. Using magnetic resonance (MR)
      imaging, the tumors were characterized by a T2-hyperintense and T1-isointense
      mass in one dog, T2- and T1-isointense extraaxial masses in two dogs, and a
      diffuse T2-hyperintense lesion over the left cerebral cortex in one dog. All
      tumors had contrast enhancement. MRI features in three of the four dogs were
      similar to that of meningioma, supported by the observation of a dural tail in
      two of these three dogs, and a broad base of attachment in the other. In the
      other dog the imaging findings were similar to those of encephalitis.
      Intracranial histiocytic sarcoma does not appear to have specific MR imaging
      features and can be confused with meningioma or encephalitis.

PMID- 19400463
TI  - The effect of manual lung inflation vs. spontaneous inspiration on the cardiac
      silhouette in anesthetized dogs.
AB  - The purpose of this study was to assess radiographic heart size in anesthetized
      dogs, comparing radiographs made with the patient breathing spontaneously to
      radiographs obtained using positive pressure manual lung inflation. The
      hypothesis was that manual inflation would cause reduction in the cardiac size.
      With dogs in right recumbency a radiograph was made at peak spontaneous
      inspiration followed immediately a radiograph made with application of positive
      pressure manual inflation of the thorax. Cardiac size was assessed, both
      subjectively and objectively using the vertebral heart scale (VHS). Two hundred
      and six dogs were studied. Manual inflation resulted in a significantly greater
      degree of lung inflation assessed radiographically (P < 0.0001). The subjectively
      assessed heart size was significantly smaller in radiographs made with manual
      inflation, leading to different subjective categorization of heart size in 67
      (32%) of dogs. The objectively measured VHS was also significantly smaller in the
      radiographs made using manual inflation by a mean of 0.24 of a vertebral length
      (95% CL of mean difference: -0.29, -0.19, P < 0.0001). A statistically
      significant reduction in subjective heart size and in VHS occurred with manual
      inflation of the lungs, and these differences may be clinically significant.
      Thus, if serial radiographs are obtained to assess cardiac size, the radiographic
      technique used should be the same.

PMID- 19400465
TI  - Imaging diagnosis--chronic canine distemper meningoencephalitis.

PMID- 19400466
TI  - Imaging diagnosis--positive contrast peritoneographic features of true
      diaphragmatic hernia.
AB  - A true diaphragmatic hernia is a congenital diaphragmatic malformation that can
      appear identical to a peritoneopericardial diaphragmatic hernia (PPDH). True
      diaphragmatic hernias are rare in dogs. Herein we describe the use of positive
      contrast peritoneography for diagnosis of a true diaphragmatic hernia in two
      dogs.

PMID- 19400467
TI  - Characterization of canine focal liver lesions with contrast-enhanced ultrasound
      using a novel contrast agent-sonazoid.
AB  - Contrast-enhanced ultrasound using Sonazoid, a novel contrast medium with a liver
      specific Kupffer phase, was evaluated in canine focal liver lesions Twenty-five
      dogs with a liver mass were given intravenous Sonazoid, and the enhancement
      pattern in the arterial, portal, and parenchymal phase was characterized. An
      enhancement defect in the lesion in the parenchymal phase was observed in all
      malignant lesions, whereas only one of nine benign lesions had a filling defect.
      The diagnostic value of the presence of a filling defect for malignancy was
      statistically significant (100% sensitivity, 88.9% specificity, 94.1% positive
      predictive value, 100% negative predictive value), and was equal to that of
      hypoenhancement in the portal or delayed phase. The defect pattern (clear or
      irregular defect) was dependent (P < 0.05) on the types of malignancy (i.e.,
      hepatocellular carcinoma and other types of malignancies). In the arterial phase,
      five of the six hepatocellular carcinomas had hypervascularity, whereas no other
      lesion was characterized by hypervascularity. In some dogs, additional lesions
      that could not be observed with conventional B-mode ultrasonography were detected
      in the parenchymal phase. The enhancement pattern of Sonazoid, especially in the
      parenchymal phase, has potential as a diagnostic tool for canine focal liver
      lesions.

PMID- 19400468
TI  - Ultrasonographic appearance of jejunal lymph nodes in dogs without clinical signs
      of gastrointestinal disease.
AB  - The jejunal lymph nodes of 57 dogs without clinical signs of gastrointestinal
      disease were examined to characterize their ultrasonographic appearance on B-mode
      and power Doppler examination, and to obtain ultrasonographic measurements. The
      lymph nodes were mildly hypoechoic to the mesentery in 71% of dogs and isoechoic
      in 29%. All dogs, 6 years of age or older had jejunal lymph nodes of uniform
      echogenicity. In dogs less than 6 years of age, nonuniform lymph nodes with
      different echopatterns were observed. Although most lymph nodes had no blood flow
      based on power Doppler examination, hilar blood flow was detected in 33% of dogs,
      which were generally less than 2 years of age. The median maximum thickness of
      the jejunal lymph nodes was 3.9 mm (range 1.6-8.2 mm), and their median maximum
      width 7.5 mm (range 2.6-14.7 mm). There was a significant correlation between
      larger lymph node diameter and younger age and higher body weight. We concluded
      that patient age should be considered when interpreting the echopattern and
      vascularity of jejunal lymph nodes in dogs, and that the jejunal lymph nodes of
      dogs without clinical signs of gastrointestinal disease may exceed the previously
      stated upper limit of 5-6 mm thickness.

PMID- 19400469
TI  - Ultrasonographic appearance of canine gastric polyps.
AB  - Benign gastric polyps are uncommon in dogs and most are discovered incidentally.
      Polyps protruding into the pyloric antrum can cause gastric outflow obstruction.
      Clinical and ultrasonographic findings in seven dogs with histologically
      confirmed benign mucosal gastric polyps were reviewed. Sonographic findings such
      as shape, size, echogenicity, location, evidence of gastric wall thickening, wall
      layering, and size of regional lymph nodes were recorded. Five sessile and two
      pedunculated masses of different sizes (range 7-60 mm) and echogenicities were
      found. They primarily arose from the mucosal layer and protruded into the gastric
      lumen. Only one dog had a large inhomogeneous mass with a poorly visualized
      gastric wall layering. The polyps were all single, and were located in the
      pyloric antrum in six out of seven dogs. Although the ultrasonographic appearance
      allowed a presumptive diagnosis of mucosal gastric polyp, the final diagnosis was
      determined from histopathologic examination.

PMID- 19400470
TI  - Ultrasonographic features of intestinal entrapment in dogs.
AB  - The clinical and ultrasonographic features of postoperative intestinal entrapment
      were assessed in five dogs. Four had vomiting and lethargy, and one had peracute
      collapse and hematochezia. Ultrasonographic findings in four of five dogs were
      similar, being characterized by focally hyperechoic mesentery and abdominal
      effusion, surrounding a single loop of amotile and dilated intestine. In some
      dogs, the affected intestinal loop had a thickened or corrugated wall, or
      alteration of wall layering. In one dog, the site of entrapment could be directly
      visualized. In the most severely affected dog, a large volume of echogenic
      peritoneal effusion was present, as well as fluid dilation of multiple intestinal
      loops. The ultrasonographic appearance of intestinal entrapment is similar to
      that of intestinal perforation or infarction by other causes.

PMID- 19400471
TI  - Scintigraphic and radiographic appearance of the sacroiliac region in horses with
      gait abnormalities or poor performance.
AB  - Nuclear bone scintigraphy is commonly used in the diagnosis of sacroiliac disease
      in horses. The aim of the present retrospective study was to determine if there
      was an association between radiopharmaceutical uptake pattern and radiographic
      appearance of the sacroiliac region in horses. Seventy-nine horses undergoing
      bone scintigraphy with Tc-99 m-HDP and radiography of the pelvis because of
      lameness or poor performance were studied. Subjective and semiquantitative
      methods were used to characterize and compare radiopharmaceutical uptake between
      horses. Ventrodorsal radiographs of the region were obtained and were evaluated.
      Subjectively, 70 horses (88.6%) had an abnormal uptake pattern. In nine horses,
      the sacroiliac region was normal (11.4%). There was no association between
      subjective evaluation of the scintigraphic images and semiquantitative methods.
      There was a significant association between radiopharmaceutical uptake and
      conformation (T- or Y-like form) and shape (butterfly-, wing-, leaf-, or horn
      like) of the sacrum. The radiopharmaceutical uptake of the tubera sacralia was
      significantly higher in males (left side P = 0.002, right side P = 0.003). In
      conclusion, the conformation of the sacrum may play an important role in the
      scintigraphic appearance and may be the cause of increased radiopharmaceutical
      uptake.

PMID- 19400472
TI  - 18FDG-PET imaging in canine lymphoma and cutaneous mast cell tumor.
AB  - Positron Emission Tomography (PET) using the glucose analog 2-deoxy-2-[18F]fluoro
      D-glucose (18FDG) is a common imaging modality for diagnosis and management of
      many human malignancies. We evaluated 18FDG-PET in dogs with either multicentric
      lymphoma (LSA) or cutaneous mast cell tumor (MCT). A prototype large field-of
      view PET scanner was used to collect whole-body images in nine dogs with LSA or
      MCT. Both tumors were characterized by avidity for 18FDG. In dogs with LSA, 18FDG
      PET correctly identified involvement of superficial and internal lymph nodes,
      liver, and spleen. Repeated PET scans after induction chemotherapy demonstrated
      resolution of abnormal 18FDG uptake within these sites. In dogs with MCT, 18FDG
      PET correctly identified MCT metastasis to regional lymph nodes in all dogs in
      which this was suspected or confirmed with cytology or biopsy before the PET
      scan. In two dogs, additional sites of mast cell disease were identified with
      18FDG-PET that were undetected on physical examination and/or regional lymph node
      cytology. 18FDG-PET holds promise as a whole-body staging method for canine LSA
      and MCT.

PMID- 19400473
TI  - Quantitative thyroid scintigraphy in greyhounds suspected of primary
      hypothyroidism.
AB  - The existence of hypothyroidism in greyhounds remains controversial and its
      investigation is complicated by the low circulating thyroid hormone
      concentrations typically found in healthy dogs of this breed. Quantitative
      measurement of thyroidal technetium-99m pertechnetate ((99m)TcO4-) uptake is
      known to be useful in assessing thyroid function in other breeds. The aim of this
      study was to evaluate thyroid scintigraphy as a method of assessing thyroid
      function in greyhounds suspected of primary hypothyroidism. Twenty greyhounds
      (eight females, 12 males) were studied. Thirteen had bald thigh syndrome and
      seven poor performance and low total T4. Total T4 concentrations were decreased
      in 18 (90%), and free T4 in two (10%) dogs. All canine thyroid stimulating
      hormone concentrations were within the reference interval. Thyroidal (99m)TcO4-
      uptake values (mean +/- SD, 0.76 +/- 0.26%) were within the reference limits
      published for euthyroid dogs (0.39-1.86%) making hypothyroidism highly unlikely.
      There were no significant differences (P < 0.05) when comparing data between dogs
      with bald thigh syndrome (13 dogs) and the remaining dogs (seven dogs). Seventeen
      (85%) dogs had higher uptake in the left thyroid gland than in the right that
      might reflect an anatomic feature of the greyhound breed. Calculation of percent
      thyroidal uptake of (99m)TcO4- is more accurate than thyroid: salivary gland
      ratios because of high variability in salivary gland uptake. Percent thyroidal
      uptake of (99m)TcO4- should be used when assessing thyroid function
      scintigraphically in the greyhound breed.

PMID- 19400474
TI  - Assessment of a radiotherapy patient cranial immobilization device using daily on
      board kilovoltage imaging.
AB  - The purpose of this study was to utilize state-of-the-art on-board digital
      kilovoltage (kV) imaging to determine the systematic and random set-up errors of
      an immobilization device designed for canine and feline cranial radiotherapy
      treatments. The immobilization device is comprised of a custom made support
      bridge, bite block, vacuum-based foam mold and a modified thermoplastic mask
      attached to a commercially available head rest designed for human radiotherapy
      treatments. The immobilization device was indexed to a Varian exact couch-top
      designed for image guided radiation therapy (IGRT). Daily orthogonal kV images
      were compared to Eclipse treatment planning digitally reconstructed radiographs
      (DRRs). The orthogonal kV images and DRRs were directly compared online utilizing
      the Varian on-board imaging (OBI) system with set-up corrections mmediately and
      remotely transferred to the treatment couch prior to treatment delivery. Off-line
      review of 124 patient treatments indicates systematic errors consisting of +0.18
      mm vertical, +0.39mm longitudinal and -0.08 mm lateral. The random errors
      corresponding to 2 standard deviations (95% CI) consist of 4.02 mm vertical, 2.97
      mm longitudinal and 2.53 mm lateral and represent conservative CTV to PTV margins
      if kV OBI is not available. Use of daily kV OBI along with the cranial
      immobilization device permits reduction of the CTV to PTV margins to
      approximately 2.0 mm.

PMID- 19400475
TI  - Use of a petroleum-based bolus for photon radiation therapy of distal extremities
      in dogs.
AB  - While skin sparing is an advantage of megavoltage beams, in certain clinical
      situations the planning target volume includes the skin surface and a skin
      sparing effect is not desirable. A tissue equivalent material, termed build up
      bolus, is used in these situations to provide adequate absorbed dose at the
      surface of the skin. However, an irregular patient contour can lead to air gaps
      between the build up bolus and the skin surface, which may result in variability
      in radiation dose across the target volume. The shape of the canine distal hind
      extremity is irregular, and commercially available bolus materials do not conform
      well to this region. The purpose of this study was to assess the dose homogeneity
      achieved using a petroleum-based bolus material, in combination with a
      commercially available sheet bolus, for radiation treatment of the canine tarsus.
      Repeated setups were performed to mimic daily treatment setups in the clinic
      setting, and computed tomographic scans were performed after each setup. Dose
      distribution achieved with a cobalt therapy machine and a 6 MV linear accelerator
      was assessed using three-dimensional treatment planning software. The dose to the
      clinicaltarget volume fell within 95% and 107% of the prescribed dose for both
      treatment machines, which is considered clinically acceptable by the authors.
      This petroleum-based bolus is equivalent to water in its photon attenuation,
      conforms well to an irregular patient contour, and retains its shape after
      positioning. Applications to other anatomical sites could be considered.

PMID- 19400476
TI  - Statistical briefing: type 1 and type 2 errors.

PMID- 19400477
TI  - Pulmonary ring-down artifacts.

PMID- 19400478
TI  - Magnetic resonance imaging findings in histologically confirmed Pug dog
      encephalitis.

PMID- 19400479
TI  - Blood pressure monitoring--the von Recklinghausen oscillotonometer.

PMID- 19400480
TI  - It's what we do everyday. Why can't we explain how it works?

PMID- 19400481
TI  - Scout's motto.

PMID- 19400483
TI  - Critical care of the patient with acute pancreatitis.
AB  - Acute pancreatitis is an inflammatory process of the pancreas with variable
      involvement of regional tissues and remote organs. This review gives a
      comprehensive overview of the aetiology, pathophysiology, diagnosis and therapy
      of acute pancreatitis relevant to the intensivist. Recent international
      guidelines on the management of acute pancreatitis are summarised. Eighty percent
      of acute pancreatitis episodes are related either to gallstones or to alcohol
      abuse. Independent of its aetiology, the pathophysiologic hallmark of acute
      pancreatitis is the premature activation of trypsin, which leads to massive
      pancreas inflammation, systemic overproduction of pro-inflammatory mediators and
      ultimately remote organ dysfunction. All guidelines agree that the diagnosis of
      acute pancreatitis should include clinical symptoms, increased serum amylase or
      lipase levels and/or characteristic findings on computed tomography. Endoscopic
      retrograde cholangiopancreatography is recommended as a causative therapy in
      patients with acute cholangitis or a strong suspicion of gallstones. All
      guidelines underline the importance of vigorous fluid resuscitation and
      supplemental oxygen therapy and prefer enteral over parenteral nutrition, with
      the majority favouring the nasojejunal route. In view of lacking scientific
      evidence, antibiotic prophylaxis to prevent infection of pancreatic necroses is
      discouraged by most guidelines. Computed tomography-guided fine needle aspiration
      is the technique of choice to differentiate between sterile and infected pancreas
      necrosis. While sterile pancreatic necrosis should be managed conservatively,
      infected pancreatic necrosis requires debridement and drainage supplemented by
      antibiotic therapy. Surgical necrosectomy is the traditional approach, but less
      invasive techniques (retroperitoneal or laparoscopic necrosectomy, computed
      tomography-guided percutaneous catheter drainage) may be equally effective.

PMID- 19400482
TI  - Some scientific reflections on possible mechanisms of general anaesthesia.
AB  - The challenge to achieve a gestalt understanding of general anaesthesia is really
      dependent upon an understanding of the elusive concept of consciousness. Until
      very recently, anaesthesia has been understood to depend fundamentally on the
      lipid solubility of anaesthetic agents, unsurprisingly a misleading view which
      has followed from the greater simplicity of lipid chemistry compared with protein
      chemistry and, it is contended here, from a serious misunderstanding of the older
      experimental data. Nonetheless, because an over-simplistic view of lipids
      pertains in much pharmacological thinking about anaesthesia, this paper devotes
      some attention to potentially relevant aspects of lipid function and also to
      concepts of anaesthesia which are based on the properties of intracellular and
      extracellular water. It is argued that the more correct pharmacological
      explanation is likely to be action at hydrophobic sites of crucial functional
      molecules, most plausibly protein molecules: empirical data which support such
      actions are presented and considered. Anaesthetic actions on a range of such
      proteins are discussed, with the emphasis on general neurophysiological
      principles, with the intent of avoiding the mire into which detailed
      consideration of actions at specific sites of putative function in the central
      nervous system can lead. Those experimentally-documented actions include
      influences on the proteins which constitute the Na(+)-ion conductance channels in
      axonal membranes (which are the basis for action potentials); on the Ca(2+)-ion
      channels which are crucial for neurotransmitter secretion from nerve terminals;
      on the properties of the ion channels in the post-synaptic membranes of the
      neurons which are the targets for transmitter action; on components of the
      "second messenger" systems of target neurons; as well as actions on metabolically
      significant enzymes (notably cytochrome P450). The overall argument is that the
      concept of anaesthetic actions on lipids should be abandoned in favour of one
      which is consistent with the general pharmacological principle of drug action at
      specific receptor sites, i.e. a targeted action at unique loci on relevant
      proteins.

PMID- 19400484
TI  - Patient sex and its influence on general anaesthesia.
AB  - Physiological and pharmacological differences exist between men and women. Women
      wake faster than men following general anaesthesia. Women also differ from men in
      their postoperative recovery as reflected by differences in postoperative pain,
      nausea and vomiting and overall quality of recovery. These gender differences
      seem to be more pronounced in premenopausal women, suggesting hormonal mechanisms
      are a major contributing factor.

PMID- 19400485
TI  - Video and optic laryngoscopy assisted tracheal intubation--the new era.
AB  - With advances in technology, videoscopy and optic intubation have been gaining
      popularity particularly in patients with difficult airways or as rescue devices
      in failed intubation attempts. Their routine use is, however an uncommon
      occurrence. This review paper will summarise some of those newly developed
      devices currently available to assist tracheal intubation, their advantages,
      disadvantages when compared with the conventional laryngoscope and finally,
      evidence to support their use in both elective and emergency airway management.

PMID- 19400486
TI  - An update on C-reactive protein for intensivists.
AB  - This review aims to summarise the physiology of C-reactive protein (CRP), its
      possible roles and limitations as an inflammatory and infective marker in
      intensive care medicine, and also the emerging roles of CRP in the pathogenesis
      of cardiovascular and autoimmune diseases. Observational and animal studies on
      uses of CRP were retrieved from the PubMed database without any language
      restrictions. Quantitative data were not pooled because of the heterogeneity of
      patient characteristics and disparate ways in which CRP was studied. Serum CRP
      concentrations are determined by the synthetic rate of its production in the
      liver regulated predominantly by interleukin-6. It has a half-life of 19 hours
      and is relatively slow in its onset and offset in response to an acute
      inflammatory process when compared to procalcitonin. It has some favourable
      properties and limitations as an inflammatory marker An elevated CRP
      concentration is not specific to infections and the absolute CRP concentrations
      cannot be used to differentiate between bacterial, fungal and severe viral
      infections. The dynamic response of CRP to therapy that aims to modify the
      underlying inflammatory process and the clinical context of a patient are of
      pivotal importance when CRP concentrations are interpreted. CRP is found to be a
      significant partaker and prognostic factor in a wide range of cardiovascular and
      chronic diseases. In summary, CRP concentration is an important prognostic factor
      of many acute and chronic diseases. Serial CRP measurements may be useful to
      reflect a patient's response to therapy that aims to modify the underlying
      inflammatory process.

PMID- 19400487
TI  - A randomised, double-blind comparison of three different volumes of hypobaric
      intrathecal bupivacaine for orthopaedic surgery.
AB  - This study was designed to evaluate different doses of hypobaric 0.15%
      bupivacaine administered to achieve unilateral orthopaedic surgery under
      subarachnoid block. Using a randomised, double-blinded protocol, 150 ASA I to II
      patients scheduled for elective unilateral orthopaedic surgery were allocated to
      received a subarachnoid block with hypobaric bupivacaine 0.15% 4.5 mg (3 ml)
      (Group 1), 6.0 mg (4 ml) (Group 2) or 7.5 mg (5 ml) (Group 3). Measurements
      included cardiovascular and haemodynamic stability, incidence of unilateral
      anaesthesia, time to recover from motor block, postoperative urinary retention,
      transitory neurological symptoms and postdural puncture headache. There was a
      dose-dependent increase in the duration of the block, from 1:55 +/- 00:20 hours
      (4.5 mg) to 2:15 +/- 00:22 hours (6.0 mg) and 3:15 +/- 00:31 hours (7.5 mg). The
      sensory block in the operated limb was significantly higher than that in the non
      operated limb at all times. The increasing dose resulted in an increase of the
      motor block score. Seventy percent of patients had unilateral block. It was
      concluded that the spinal anaesthesia in all groups was suitable for single limb
      orthopaedic surgery. The smallest dose (4.5 mg) of hypobaric 0.15% bupivacaine
      resulted in more unilateral blocks, with narrower distribution and shorter
      duration.

PMID- 19400488
TI  - Intraoperative ketamine may influence persistent pain following knee arthroplasty
      under combined general and spinal anaesthesia: a pilot study.
AB  - We report the findings of a randomised controlled triple-blind pilot study of
      intraoperative ketamine infusion combined with spinal anaesthesia on the
      prevalence of persisting post surgical pain following total knee arthroplasty
      surgery. Twelve patients were randomised to receive either ketamine or placebo in
      association with spinal anaesthesia for total knee arthroplasty. All patients
      also received general anaesthesia. More patients were pain-free at six months in
      the ketamine group (three of five) compared to the control group (two of seven).
      Perioperative data collected during the study suggested that the addition of
      intraoperative ketamine might also improve the quality of recovery. Although no
      statistical analysis was undertaken due to the small numbers, these preliminary
      findings suggest that the use of intraoperative systemic ketamine in association
      with spinal anaesthesia for the reduction of persisting post surgical pain
      deserves further study.

PMID- 19400489
TI  - Prevalence of vitamin deficiencies on admission: relationship to hospital
      mortality in critically ill patients.
AB  - Vitamin deficiency is believed to be common in critical illness. Water soluble
      and antioxidant vitamins are those most frequently used for supplementation in
      these patients. There are no data to confirm the prevalence of vitamin
      deficiencies in high-risk emergently admitted intensive care patients, nor their
      association with hospital mortality. One hundred and twenty-nine consecutive,
      critically ill patients who were emergently admitted to intensive care were
      enrolled in this prospective observational cohort study. Patient data including
      diagnosis, source of admission and severity of illness scores were prospectively
      collected. Within the first 48 hours of admission, concentrations of C-reactive
      protein, Vitamins A, E, B1, B12 and folate were measured on arterial blood.
      Multivariate stepwise logistic regression modelling was performed to examine the
      association of vitamin concentrations with hospital mortality. Fifty-five
      patients (43%) had a biochemical deficiency of one of the five vitamins on
      admission to the intensive care unit. A total of 18 patients died (14%) during
      their hospital stay (15 of those in the intensive care unit). Moderate
      correlations with C-reactive protein concentrations were demonstrated for
      Vitamins B12, A and E (Spearman's r = 0.309, -0.541 and -0.299, P = 0.001, 0.001
      and 0.007 respectively). Hospital mortality was significantly associated with
      age, APACHE II score, admission and maximum Sequential Organ Failure Assessment
      scores and admission source in the univariate analyses. Multivariate analysis did
      not demonstrate an association between biochemical deficiency and mortality.
      Biochemical deficiencies of water-soluble and antioxidant vitamins are common on
      admission in unplanned or emergency admissions to the intensive care unit, but we
      could not demonstrate an independent association with hospital mortality.

PMID- 19400490
TI  - The effect of increasing operating room capacity on day-of-surgery cancellation.
AB  - Several studies have been conducted to evaluate the utilisation of the operating
      room, a fixed resource, in terms of conditions that prevent day-of-surgery
      cancellation due to deficient operative capacity. In this study, we surveyed the
      causes and overall rates of elective surgery cancellation and then compared the
      number of cancellations that occurred before and after the installation of
      additional operating rooms. We surveyed all patients undergoing elective surgery
      for 100 days prior to and after the installation of additional operating rooms.
      The causes for cancellations were divided into six categories: departmental
      issues, abnormal laboratory results, patient denial, inadequate preparation, over
      booking and other issues. The departmental causes were further divided into four
      categories: ward overflow, scheduling date errors, unavailable surgeons and other
      issues. The number of overall cancelled cases and scheduled cases increased
      following the increase in operating room capacity, although this increase was not
      statistically significant. However; the cancellation ratio rose significantly
      after the operating room capacity was increased. The primary reasons for
      cancellation prior to the increase in operating room capacity were departmental
      issues, over-booking and abnormal laboratory data, in that order. After the
      operating room capacity was increased, the primary reasons for cancellation were
      departmental issues, abnormal laboratory data and over-booking, in that order
      Taken together the results of this study indicate that increased operating room
      capacity can prevent cancellation due to over-booking. However; the numbers of
      cancellations due to ward overflow exceeded the numbers of cancellations that
      occurred as a result of over-booking. In conclusion, increasing the operating
      room capacity is not an appropriate option for preventing the cancellation of
      operations.

PMID- 19400491
TI  - Opioid abuse amongst anaesthetists: a system to detect personal usage.
AB  - Substance abuse continues to be a significant problem amongst anaesthetists. We
      have investigated a run chart methodology for tracking opioid use that may be
      used to identify potential personal use by noting a change in usage over time.
      Included in the data set was a record of an anaesthetist who abused opioids.
      Opioids signed out from the controlled drugs safe were converted into generic
      units so that opioid use could be compared. These standardised units of usage
      were plotted against anaesthetists' theatre time. We show, using run charts--a
      method used in industrial quality control--how abnormal usage could have been
      detected. The key to the run chart methodology is detection in a change in
      personal use rather than demonstrating any change compared with departmental
      averages. More time series data from anaesthetists known to have abused opioids
      would be required to validate the system.

PMID- 19400492
TI  - A national survey on the practice and outcomes of mechanical ventilation in
      Korean intensive care units.
AB  - A study was undertaken to describe the practice and outcomes of mechanical
      ventilation throughout Korea. This prospective cohort study was conducted over a
      three-month period enrolling patients (n = 519) who received mechanical
      ventilation for more than 72 hours in 21 university hospital intensive care units
      throughout Korea. The most common indication for mechanical ventilation was acute
      respiratory failure. The most common cause of acute-on-chronic respiratory
      failure was tuberculous lung disease. The most common initial mode for
      ventilation was volume-controlled ventilation. The mean tidal volume of acute
      respiratory distress syndrome patients was 7.6 ml/kg of the predicted body weight
      and the mean positive end-expiratory pressure was 9.4 cmH20. The weaning success
      rate at 28 days was 50.3%. Pressure support and the T-piece were most commonly
      used as initial and final weaning modes respectively. Preventive measures against
      deep vein thrombosis during mechanical ventilation were performed more frequently
      in intensive care units with full-time critical care physicians than those
      without such physicians. Multivariate analysis showed that the APACHE II score,
      indication for mechanical ventilation, respiratory rate at 72 hours, enteral
      feeding and prophylaxis of deep vein thrombosis were prognostic factors for
      survival. In Korean intensive care units, tuberculous lung disease remains an
      important cause for mechanical ventilation. The practice of mechanical
      ventilation in Korean intensive care units in general appeared to comply with the
      current international recommendations with regard to lung protection and weaning.
      However, intensive care units lacking critical care physicians seemed to be
      adopting fewer ancillary measures, such as deep vein thrombosis prophylaxis.

PMID- 19400493
TI  - No elevation of glutathione S-transferase-a1-1 by amiodarone loading in intensive
      care unit patients with atrial fibrillation.
AB  - Hepatocellular toxicity is a putative side-effect of amiodarone. The hepatic
      detoxification enzyme glutathione S-transferase-A1-1 (GSTA1-1) is a sensitive
      indicator of hepatocellular damage. We investigated the occurrence of subclinical
      liver injury, as measured by plasma GSTA1-1 in intensive care unit patients with
      atrial fibrillation receiving amiodarone. Sixteen haemodynamically stable
      intensive care unit patients with atrial fibrillation were treated with
      amiodarone intravenously. Patients were given a loading dose of 150 mg followed
      by another 150 mg followed by a continuous infusion of 1200 mg/hour if atrial
      fibrillation persisted. Blood samples for GSTA1-1 (measured by an enzyme-linked
      immunosorbent assay) were taken at zero, one, three, six, 12 and 24 hours,
      transaminases and bilirubin at zero, six, 12 and 24 hours. Blood pressure and
      heart rate were continuously monitored. Effects were analysed for time-dependent
      changes (one-way analysis of variance for repeated measures). Blood pressure
      increased from 125 +/- 8/60 +/- 3 mmHg at t = 0 to 144 +/- 9/66 +/- 4 mmHg at t =
      24 hours (P < 0.05), heart rate decreased from atrial fibrillation 124 +/- 5 to
      sinus rhythm 86 +/- 6 beats per minute (P < 0.05). There was no significant
      elevation of GSTA1-1, transaminases or bilirubin during the observation period of
      24 hours. Amiodarone does not cause elevation of GSTA1-1 as a marker of
      subclinical liver injury in haemodynamically stable intensive care unit patients
      with atrial fibrillation.

PMID- 19400494
TI  - Outcome of patients receiving high dose vasopressor therapy: a retrospective
      cohort study.
AB  - The aim of this study was to determine the hospital survival of patients
      receiving high doses of catecholamines. A retrospective observational study was
      conducted in a 22-bed multidisciplinary adult intensive care unit of a tertiary
      referral university hospital. All patients (n = 64) receiving > 100 microg/min of
      adrenaline or noradrenaline or adrenaline and noradrenaline combined over a one
      year period were studied to determine survival to intensive care unit and
      hospital discharge. Four patients survived to intensive care unit discharge and
      hospital discharge (6.25%, 95% CI 0.3 to 12.2%). Survival was 3.3% (95% CI 0 to
      7.9%) in the subgroup of 60 patients who received > 100 microg/min noradrenaline
      and 3.6% (95% CI 0 to 8.6%) in the 55 patients who received > 2 microg/kg/min
      noradrenaline. None of the 32 patients who received > 200 microg/min
      noradrenaline survived. We conclude that the survival of patients requiring high
      doses of catecholamines is poor but the use of such doses is probably not futile.
      It remains for individual clinicians, patients and their surrogates to decide
      whether use of high doses of vasopressor is appropriate, given the low
      probability of survival.

PMID- 19400495
TI  - The pulmonary artery catheter sleeve--protective or infective?
AB  - The use of sterile plastic sleeves to protect pulmonary artery catheters (PAC)
      may decrease infection risk. The catheter may require manipulation but
      contamination of the sleeve risks inoculating organisms into the patients. We
      sought to determine whether the sleeve remains sterile and for how long. We
      conducted a prospective observational study to culture the components of the PAC
      in a critically ill population. Upon removal we cultured 1) the PAC tip, 2) the
      PAC introducer exit site, 3) the PAC introducer hub and 4) a sterile irrigant
      solution which ran down the inside of the protective sleeve. Demographic,
      catheter and disease variables were also collected. There were 102 PAC episodes
      amounting to 3952 catheter hours with a mean duration of catheterisation of 39.1
      (24.2) hours. There were 17 positive culture results, of which six were positive
      sleeve fluid cultures. In three of these patients the exit site was culture
      positive, and the same organism was isolated as within the sleeve. No patient had
      a positive blood culture. There was no difference between those with and without
      a positive sleeve culture in terms of demographic or disease variables. The
      protective sleeve of the pulmonary artery catheter does not remain sterile and
      should not be considered as a sterile barrier. We believe that manipulating the
      PAC within the sleeve carries the risk of inoculating the patient with pathogenic
      organisms. The duration of sterility remains to be determined.

PMID- 19400496
TI  - Fibreoptic intubation under general anaesthesia--a simple method using an
      endotracheal tube as a conduit.
AB  - A novel technique for management of the difficult airway is described. The case
      report describes fibreoptic intubation of a patient who refused awake intubation.
      An endotracheal tube was advanced as far as the nasopharynx via the nostril of
      the patient, under anaesthesia. Connection of the anaesthetic circuit allowed
      maintenance of anaesthesia, oxygenation and assisted ventilation while flexible
      bronchoscopy was performed through the tube via a bronchoscopy connector The
      endotracheal tube was subsequently advanced over the bronchoscope into the
      trachea. This technique uses readily available materials and can be used where
      the placement of a laryngeal mask is contraindicated or impossible.

PMID- 19400497
TI  - Magnetic resonance scanning of the upper airway following difficult intubation
      reveals an unexpected lingual tonsil.
AB  - We present a case of a 40-year-old woman requiring elective surgery who had an
      unexpected Grade 4 Cormack and Lehane laryngoscopy view. Both curved and straight
      laryngoscope blades in the sniffing and hyperextended head and neck positions
      were used. Endotracheal intubation was accomplished with some difficulty using a
      No. 3 Macintosh blade and Frova intubating catheter in the sniffing position. The
      cause of the difficult laryngoscopy was a lingual tonsil as shown in
      postoperative magnetic resonance scans. We feel that a comprehensive
      postoperative evaluation should be conducted after every difficult laryngoscopy
      (Cormack and Lehane Grade 3b and 4). The use of magnetic resonance imaging may
      provide important objective information for both the anaesthetist and the
      patient, allowing a better understanding of causes and possible solutions for
      future airway management.

PMID- 19400498
TI  - Labour management of a woman with carnitine palmitoyl transferase type 2
      deficiency.
AB  - Carnitine palmitoyl transferase (CPT) type 2 deficiency is a disorder of
      mitochondrial fatty acid oxidation. In situations where energy stores are
      inadequate, such as may occur during labour women with CPT type 2 deficiency are
      at risk of rhabdomyolysis. There is limited experience in the management of women
      with this condition in labour. We report a case of successful labour management
      of a woman with CPT type 2 deficiency, together with a brief review of the
      published case reports and a discussion of the issues surrounding anaesthetic
      management.

PMID- 19400499
TI  - Airway obstruction due to a pre-vertebral haematoma following difficult central
      line insertion--implications for ultrasound guidance and review of the
      literature.
AB  - We describe a case of airway obstruction secondary to a large pre-vertebral
      cervico-mediastinal haematoma following failed attempts at insertion of an
      internal jugular central venous line. The need for a high index of suspicion to
      diagnose this injury and early aggressive intervention to manage it are outlined.
      The role of ultrasound guidance in preventing such a complication is reviewed, as
      well as other possible mechanisms of haematoma development.

PMID- 19400500
TI  - A patient with intractable posthypoxic myoclonus (Lance-Adams syndrome) treated
      with sodium oxybate.
AB  - Posthypoxic myoclonus is a rare and devastating complication of near-fatal
      cardiopulmonary arrest. Despite treatment with available anti-myoclonic agents,
      some patients may recover cognitively but remain completely disabled by severe
      myoclonus. We report a 16-year-old patient with severe treatment-refractory
      posthypoxic myoclonus, which improved markedly with administration of the drug
      sodium oxybate.

PMID- 19400501
TI  - Diabetes insipidus following overdose of baclofen and quetiapine.
AB  - We report the case of a patient who presented with coma in the context of
      baclofen and quetiapine overdose. While the clinical picture was largely in
      keeping with previous descriptions of baclofen and quetiapine toxicity, the
      patient went on to exhibit clinical and biochemical features of cranial diabetes
      insipidus, a finding which has not previously been described in this context.

PMID- 19400502
TI  - E-letters: a caution.

PMID- 19400503
TI  - Mechanisms, management and measurement in atropine induced hyperthermia.

PMID- 19400504
TI  - The serendipitous origin of ultrasound-guided regional anaesthesia.

PMID- 19400505
TI  - Hazard of using compact dial oxygen regulator/ flowmeter.

PMID- 19400506
TI  - Complication of submental intubation.

PMID- 19400507
TI  - A preliminary evaluation of the Endoflex endotracheal tube as an alternative to a
      rigid styletted tube for Glidescope intubations.

PMID- 19400508
TI  - Persistent low capillary blood glucose estimated by the fingerstick method may be
      an early indicator of limb ischaemia in hypotensive patient requiring high
      inotropic support.

PMID- 19400509
TI  - The Rendell Baker Soucek paediatric mask in adult difficult airways.

PMID- 19400510
TI  - Glucagonoma: anaesthetic management.

PMID- 19400511
TI  - Fibreoptic bronchoscope guided tracheal intubation via facemask in apnoeic
      patients.

PMID- 19400512
TI  - Role reversal during external laryngeal manipulation for tracheal intubation--an
      alternate approach!

PMID- 19400513
TI  - Two cases of Menkes disease: airway management and dental fragility.

PMID- 19400514
TI  - [Screening of metabolic syndrome in the perimenopause].
AB  - BACKGROUND: There are few studies conducted in Mexico on increasing rates of
      cardiovascular diseases in postmenopausal patients with metabolic syndrome.
      OBJECTIVE: To determine frequency of metabolic syndrome in women of 40 to 55
      years old, that are in perimenopause and go to the external consultation of the
      Materno Infantil Inguaran Hospital. MATERIAL AND METHODS: We made transversal,
      observational, and prospective study, including women of 40 to 55 years old, that
      went to external consultation of the Materno Infantil Inguaran Hospital, since
      January to June 2007 (n=60). To all the patients it was taken them blood samples
      in uninformed stop to value glucose, triglycerides, HDL, pressure blood and Body
      Measure Index and wais-to-hip ratio. RESULTS: The patients went to the Hospital
      by gynecologic pathology. We found Metabolic Syndrome frequency and the abnormal
      factors were triglyceride, waist circumference. We found high frequency
      hypertrglyceridemia and central obesity. CONCLUSIONS: In the perimenopause
      patients, to exist high frequency and predominance in the 40 and 50 years old,
      hers were asymptomatic. Before to be important to made screening in this
      patients, be cheap, and we can to prevent chronic disease such as Diabetes
      Mellitus Type 2 and Arterial Hypertension. Increase quality of live in this group
      of patients.

PMID- 19400515
TI  - [Prevalence of chromosomal alterations in infertile patients studied in a clinic
      of assisted reproduction].
AB  - BACKGROUND: Chromosomal abnormalities are a frequent cause of infertility. There
      is not consensus if should be included in the work-up of infertile couple.
      OBJECTIVE: to evaluate the prevalence of chromosomal abnormalities in our
      population of infertile couple and support the cytogenetic exam in the initial
      protocol. PATIENTS AND METHODS: Retrospective study of 787 infertile patients
      divided in five groups, to whom a cytogenetic exam was performed between January
      2004 and April 2007. RESULTS: The prevalence of general chromosomal abnormalities
      was 12.5% (98/787). We found a 14.8% (34/229) with severe male factor, 14.3%
      (2/14) with premature ovarian failure, 12.3% (20/162) with recurrent pregnancy
      loss, 8% (9/112) idiopathic infertility and 12.2% (33/270) associated with other
      causes. The major alterations correspond to trisomies, translocations, and 9
      chromosome markers. CONCLUSIONS: The results of this study are consistent with
      those reported in the literature which are associated with a greater prevalence
      of chromosomal abnormalities in infertile couples compared with the general
      population, this findings show the importance of consider the cytogenetic study
      in the initial diagnosis protocol of infertile couple.

PMID- 19400516
TI  - [Sociodemographic characteristics of users of the contraceptive implant releasing
      etonogestrel].
AB  - BACKGROUND: The search for options for contraception has always led to the
      development of increasingly effective methods and safe and, above all, varied for
      those with any contraindication to always find a viable alternative. OBJECTIVE:
      To know the sociodemography characteristics the users of implants liberating
      contraceptive of etonogestrel and the effects in the 24 following months to its
      application. MATERIAL AND METHODS: A cross-sectional descriptive study was made
      in 207 users of implants liberating of etonogestrel during 24 months in the
      Aguascalientes Delegation of IMSS through a structured questionnaire. The
      Statistic Program v 7 for the capture, data processing and analysis of were used.
      RESULTS: The group of more frequent age was of 25-29 years; the majority had at
      least secondary, lived in the urban middle, were married and catholic; 48.6% were
      dedicated to the home; 1.2% of the pairs did not work; 82.6% had a weekly sex at
      least; 84.3% had 1 to 2 children; 66.3% wished more children; 95.9% of the pairs
      approved the method; 29:6% referred a not planned previous pregnancy ; 72.1% used
      some contraceptive method previously; 36.6% referred bad experience with the
      previous method; 41.9% requested implants by comfort; 90:1% received information
      of the method but only 73.8% knew the indirect effect; 86.6% would recommend it;
      11.6% left the method by undesirable effects of which the main one was the
      irregular bled one, whereas 33.1% did not present/display any indirect effect and
      no patient became pregnant during the time of study. CONCLUSIONS: It subdermal
      implant is a contraceptive alternative adapted by its effectiveness, its
      tolerance and the high rate of continuity, finding like basic characteristics of
      the users: young woman, with acceptable educative and economic level, low parity
      and desires of future fertility.

PMID- 19400517
TI  - [Usefulness of the qualitative detection of hCG in cervicovaginal lavage for the
      diagnosis of premature rupture of membranes].
AB  - BACKGROUND: The detection of human chorionic gonadotropin (hCG) in cervicovaginal
      lavage has proved useful in establishing the diagnosis of premature rupture of
      membranes, but the methods used for determining time-consuming. OBJECTIVE: To
      qualitatively determine the concentration of hCG in cervicovaginal lavage to
      establish the diagnosis of premature rupture of membranes. PATIENTS AND METHODS:
      Prospective observational study conducted in 149 pregnant women divided into
      three groups: group I (n = 50), patients with premature rupture of membranes,
      group II, with suspected ruptured membranes and group III, with premature rupture
      of membranes confirmed. The diagnosis was established by clinical examination and
      testing nitrazina and crystallography. In all patients was conducted and
      cervicovaginal lavage fluid obtained hCG was determined with a rapid qualitative
      test (sensitivity 25 mlU/mL). We calculated the sensitivity, specificity and
      positive and negative predictive value of the method. RESULTS: The mean
      gestational age was 34.6 +/- 5.2 weeks. In 8.7% of the cases were considered
      "inconclusive" qualitative hCG test, so only 136 samples were analyzed. The
      sensitivity was 95.6%, specificity 100%, the positive predictive value of 100%
      and negative 97.8%. CONCLUSION: The qualitative determination of hCG in
      cervicovaginal lavage is useful for establishing the diagnosis of premature
      rupture of membranes.

PMID- 19400519
TI  - [Twin pregnancy with complete mole and coexisting fetus after in vitro
      fertilization and embryo transfer complicated with placenta previa accreta. A
      case report].
AB  - The double twin pregnancy with complete hydatidiform mole and coexistent fetus is
      a rare event and perinatal treatment complex. Presents a significant case of this
      unusual partnership and describes their evolution. Patient of 33 years, secondary
      infertility factor-peritoneal tube and pregnancy achieved by in vitro
      fertilization and embryo transfer. An ultrasound early pregnancy reported twice,
      a sack was a complete mole, another bag was a fetus and placenta previa unchanged
      total. The case is carefully monitored and uterine inhibitors were administered
      at different stages of gestation. It settled the case by caesarean section at 37
      weeks and obstetric hysterectomy for placenta previa percreta molar involution of
      the placenta and newborn health. The evolution of the mother and the child was
      appropriate.

PMID- 19400518
TI  - [Perinatal mortality in multiple pregnancies].
AB  - BACKGROUND: The incidence of multiple pregnancies has increased over the last
      decade and hence the hospital stay and perinatal morbidity and mortality.
      OBJECTIVE: to know the perinatal mortality rate of multiple pregnancies treated
      in a regional hospital. MATERIAL AND METHODS: Retrospective study conducted from
      the hospital records of deaths that occurred from January 2002 to December 2007
      at the Hospital Regional de Especialidades No. 23 IMSS, Monterrey, Nuevo Leon,
      Mexico. RESULTS: during the study period (six years) were 122,822 births and 95
      were multiple pregnancies (0.77/1000 births): 81 (85%) of triplets, 11 (11%) of
      quadruplets, two of quintillizos and one sextillizos with a total of 303
      newborns. 26% (25/95) of multiple pregnancies had one or more deaths. The
      perinatal mortality rate was 165/1000 births (50/303) compared with that of
      pregnancies with one fetus in the same period 14.5/1000 births (p<0.0001). 20.9%
      (17/81) of triplet pregnancies and 54.5% (6/11) of the four had one or more
      deaths (p<0.02), with a perinatal mortality rate of 131/1000 births (32/243) and
      295/1000 births (13/44) (p<0.006), respectively. Only 2/10 (20%) of newborns in
      two pregnancies quintillizos died and 3/6 (50%) of a pregnancy sextillizos. There
      was no difference in the proportion of sexes, but in the average weight of
      newborns: the weight of the triplets was alive vs dead vs 1659 g 713 g (p<0.0001)
      and the quadruplets from 750 g vs 1341 g (p<0.0007), respectively. CONCLUSIONS:
      26% of multiple pregnancies had one or more deaths and 15% of the neonates died
      (165/1000 births). Multiple pregnancies were complicated with one or more deaths
      at 20% of triplets, 54% of quadruplets and 100% of quintillizos. The perinatal
      mortality rate of pregnancies with multiple fetuses 3 and 4 was No. 131/1000 and
      No. 295/1000, respectively.

PMID- 19400520
TI  - [Chorea gravidarum. A case report].
AB  - Chorea gravidarum is an uncommon condition characterized by involuntary
      movements, speaking alterations and in the affective status during first
      trimester pregnancy, the incidence is 1 by each 2275 pregnancies, it is self
      limiting and resolves when the pregnancy ends, most of the cases are idiopathic
      and the rest is associated to the antiphospholipid syndrome, rheumatic fever,
      thyrotoxicosis, systemic lupus erythematosus, syphilis, Huntington disease or
      induced by drugs. The recurrences can occur in the subsequent pregnancies. The
      dopamine antagonists as the haloperidol and the chlorpromazine are useful to
      control the symptoms and are safe at lower doses. A 22 years-old patient, second
      pregnancy, without prenatal care, who was admitted to the labor at 36.1 weeks of
      gestation and psychosis of pregnancy presenting involuntary movements, dysnea and
      behavior disorder of three days evolution. The initial treatment was with
      diazepam, two days after the patient presented amniotic rupture without uterine
      activity, the pregnancy was interrupted by C- section and a male newborn was
      obtained. She had a favorable evolution during puerperium. She was discharged of
      the hospital four days later, having only abnormal movement in the right hand.
      Antistreptolysins antibodies of 333, PCR 1:80 and negative rheumatoid factor. She
      had four normal pregnancies more after, being the last the 10th of February of
      2007.

PMID- 19400521
TI  - [Suburethral cyst. A case report].
AB  - Suburethral cysts are rare, are formed from remnants of embryonic or blockage of
      the paraurethral glands, whose location in more than 85% of cases are found in
      the proximal two thirds and posterior and lateral to the urethra. The diagnosis
      is clinical and radiological studies are needed to demonstrate the absence of
      communication with the urethra. Once the diagnosis of suburethral cyst, surgery
      is the treatment of choice. Before its resection, the presence of a urethral
      diverticulum. Urethral injury is the most common surgical risk, as noted during
      surgery must be repaired immediately. So far it has not been reported urethra
      vaginal fistula as a complication after repair. The present patient had a cyst in
      the distal third of Suburethral 4 x 2 cm, a 6-month follow-up remained
      asymptomatic, with no postoperative complication. The pathology reported wall 3 x
      2.2 cm with a thickness of 0.3 cm, greyish, irregular, soft consistency.
      Microscopically identified transitional epithelium and foci of squamous
      metaplasia and focal chronic inflammation. According to the histopathological
      report, the transitional epithelium indicates the cyst Skene.

PMID- 19400522
TI  - [Varices and gravid puerperal state. 1954].

PMID- 19400523
TI  - [Prenatal monitoring in adolescents: risk maternal-infant].

PMID- 19400524
TI  - Reperfusion therapy in ST-segment elevation myocardial infarction in the Veteran
      Administration Caribbean Healthcare System; search for improvement.
AB  - BACKGROUND: Patients that present with acute STEMI have proven morbidity and
      mortality benefit from early reperfusion therapy. The American College of
      Cardiology/American Heart Association (ACC/AHA) guidelines recommend either
      fibrinolytic therapy within 30 minutes or a primary percutaneous coronary
      intervention (PPCI) within 90 minutes of patients arrival to the Emergency
      Department. Despite these recommendations, some patients do not receive
      reperfusion therapy and less than half receive it on time. OBJECTIVES: Describe
      and analyze our reperfusion therapy performance in patients presenting with acute
      ST segment elevation myocardial infarct (STEMI) in the Veteran Administration
      Caribbean Healthcare System (VACHS), and determine potential causes for
      reperfusion therapy delays and develop strategies and a tailored algorithm
      according to our clinical findings and available institutional resources.
      METHODS: Retrospective analysis of patients admitted to the VACHS with a
      discharge diagnosis of STEMI, from 01/01/2007 until 04/10/2008. RESULTS: A total
      of 55 patients met inclusion criteria for STEMI diagnosis. Of these, only 30
      patients had active indication for reperfusion therapy. Reperfusion therapy was
      given in 97% of the cases, 69% with PPCI and 31% with fibrinolytic therapy
      (tenecteplase). In general the selection of reperfusion therapy seemed adherent
      to ACC/AHA STEMI guidelines. The reperfusion time goal was superior with
      thrombolytic therapy compared to PPCI, with 43% and 15% respectively. PPCI
      performed off regular tour of duty was significantly delayed compared to regular
      day shift, with a mean time of 221 and 113 minutes respectively (p=0.027).
      CONCLUSIONS: Most of the patients presenting with STEMI to the VACHS undergo
      reperfusion therapy. PPCI was the most frequent selected reperfusion approach.
      The PPCI time goal was infrequently met. The most significant cause for PPCI
      delay was related to performance off regular tour of duty. These finding support
      the implementation of a tailored STEMI reperfusion algorithm favoring timely
      reperfusion.

PMID- 19400525
TI  - Quick method for mean frontal QRS axis determination.
AB  - BACKGROUND: ECGs are the recording of the electrical activity of the heart. The
      direction of it's current in the frontal plane can be determined by analyzing the
      QRS direction and magnitude in limb leads. Several methods for determination of
      the QRS frontal axis have been proposed, however most of them require
      memorization of the exact location of the leads in the frontal plane with pen and
      paper calculations. METHODS: a new method of estimating the frontal mean QRS axis
      in the standard 12 lead ECG is proposed. This method consists of assigning pre
      determined values to each frontal lead in ECGs, which have a positive or
      isoelectric QRS complexes in lead, I. The mnemonic "+/- 90, -30, +30, -60, +60,
      and 0" is obtained by plotting only the value of the axis which is perpendicular
      to the each lead on the left side of the hexaxial system. The right-sided
      perpendiculars are not considered since lead I indicates a left sided axis. The
      most isoelectric lead will have only one value plotted and that will be the mean
      QRS axis in the frontal plane. By finding the most equiphasic lead(s) and
      matching the corresponding pre-determined value we can estimate the frontal mean
      QRS axis in most of the cases. Interpolation between two leads is allowed if no
      single isoelectric lead is identified. We reviewed the standard 12 lead
      electrocardiograms of 155 patients who underwent open-heart coronary
      revascularization procedures at the VA Caribbean Health Center from 2003 to 2006.
      Frontal mean QRS axis was determined by the proposed new methodology and the
      results were compared to the QRS axis determined by the GE Marquette 5000
      electrocardiographer utilized in all the reviewed ECG's. Simple regression
      analysis was used to determine the proposed methods predictive accuracy. RESULTS:
      We obtained a high coefficient of determination R2= 0.9505, p<0.001. The derived
      linear equation was obtained as follow: y = 1.0007 + 0.9580x (Where independent
      x= QRS axis estimated by the new method, dependent y = QRS axis estimated by ECG
      machine). CONCLUSION: The proposed new method is simple and is able to estimate
      accurately the ECG frontal axis as compared with the GE Marquette 5000
      electrocardiographer in most of the cases.

PMID- 19400526
TI  - Prevention of infective endocarditis: a review of the American Heart Association
      guidelines.
AB  - Ever since the last American Heart Association (AHA) publication on prevention of
      infective endocarditis (IE) many medical societies and physicians have questioned
      the efficacy of prophylaxis in patients that undergo a dental, genitourinary (GU)
      or gastrointestinal (GI) procedures. In 1997 AHA recognize that most cases of IE
      were not related to invasive procedures but as a result of arbitrarily occurring
      bacteremia from routine daily activities as well as recognition of the
      possibility of IE prophylaxis failure. This assumptions as well as review of
      numerous published studies over the past two decades caused that AHA to revise
      the guidelines of 1997. Based on published series this new guidelines identify
      the following underlying cardiac conditions with an increase risk of IE and are
      the ones in which prophylaxis is recommended. They include (1) prosthetic cardiac
      valve or prosthetic material used for cardiac valve repair, (2) previous IE, (3)
      Congenital Heart Disease (CHD) including unrepaired cyanotic as well as
      palliative shunts and conduits, completely repaired congenital heart defect with
      prosthetic material or device during the first six months after the procedure,
      repaired CHD with residual defects and (4) cardiac transplantation recipients who
      develop cardiac valvulopathy. All dental procedures that involve manipulation of
      gingival tissue or the periapical region of teeth or perforation of the oral
      mucosa will require IE prophylaxis. Patients that undergo respiratory tract
      procedure that involves incision or biopsy of the respiratory mucosa will also
      required IE prophylaxis. In contrast to previous AHA guidelines, antibiotic
      prophylaxis to prevent IE is not recommended for GU or GI procedures. First line
      therapy recommended includes amoxicillin or ampicillin and if allergic to
      penicillin, clindamycin 600 mg or azithromycin 500 mg. Antibiotics should be
      administered in a single dose before the procedure, but the dosage may be
      administered up to two hours after procedure. This new AHA recommendation are
      more clear for healthcare providers regarding to which patient should undergo
      prophylaxis in comparison with previous ones and are expected to reduce
      antibiotic resistance that increased during the past years as a result of
      previous antibiotic prophylaxis for IE.

PMID- 19400527
TI  - Congestive heart failure and renal complications.
AB  - Congestive heart failure is the leading cause of hospital admission among
      patients over the age of 65 years. It affects population within the United
      States, including Puerto Rico, presenting itself as the leading cause of heart
      related deaths worldwide. Its management can include pharmacologic agents which
      will affect neuroendocrine axis mainly but also include novel non-pharmacologic
      approaches such as ultrafiltration. The coexistence of heart failure and renal
      dysfunctions are very common within our medical community, especially within the
      western hemisphere, causing greater concerns amongst the medical field with
      increased research and investigation activity. This clinical review article will
      address the theme of congestive heart failure, highlighting the edema formation
      concept, volume homeostasis, cardio-renal syndrome and neuroendocrine pathways.
      The management of acute decompensated heart failure is discussed, primarily
      focusing with available novel non-pharmacologic approaches.

PMID- 19400528
TI  - Management of chronic stable angina pectoris.
AB  - Agina pectoris is a discomfort in the chest or adjacent areas caused by
      myocardial ischemia. It is most commonly caused by the inability of narrowed
      atherosclerotic coronary arteries to supply adequate oxygen to the heart under
      conditions of increase demand. This review article will focus in the medical
      treatment of chronic stable angina, with a focus in new strategies or
      medications. Treatment by revascularization techniques will not be discussed in
      this article. The goal of treatment is to improve quality of life, decrease
      cardiovascular events and mortality. All patients should be evaluated for
      reversible causes of their angina, such as anemia, hyperthyroidism,
      sympathomimetic drugs and hypertension. Sublingual nitroglycerin should be used
      for immediate relief of symptoms. In general, all patients should be on aspirin
      (ASA) unless they are allergic or other contraindications, if so; clopidogrel
      should be added to the therapy. In addition to the antiplatelet therapy, which
      decreases mortality, patients should be started on beta blockers and nitrates. If
      there is no improvement in symptoms then a calcium channel blockers of the
      dihydropyridine family should be added. Patients with Diabetes Mellitus and/or
      left ventricular systolic dysfunction should be also started on angiotensin
      converting enzyme inhibitors. If the patient continues with limiting angina,
      ranolazine should be started and finally enhanced external counterpulsation
      should be considered in those patients who have not responded to maximal drug
      therapy.

PMID- 19400529
TI  - Primary cardiac and pericardial tumors.
AB  - Primary cardiac tumors are rare, with a reported prevalence of 0.001 to 0.03% at
      autopsy series. Almost 75% of all primary tumors of the heart are benign, with
      primary malignant tumors accounting for the other 25%. Nearly half of the benign
      cardiac tumors are myxomas. Other primary tumors include papillary fibroelastoma,
      rhabdomyoma, fibroma, lipoma and hemangioma. In this review article, the
      clinical, pathologic and diagnostic feature of primary benign cardiac tumors is
      presented. In very rare occasions malignant tumors of the heart could be
      encounter such as primary sarcomas of the heart constituting less than 25% of
      primary cardiac tumors found in clinical practice. Cardiac sarcomas represent the
      commonest histology of primary malignant cardiac tumors, with angiosarcomas
      making up 33% of the cases. Sarcomas are common between the third and fifth
      decades of life and most frequently affect the right atrium.

PMID- 19400530
TI  - Valvular heart disease in pregnancy: a review of the literature.
AB  - The population of pregnant women with valvular heart disease represents a unique
      patient group with increased risk for adverse outcomes. The significant
      hemodynamic changes that occur during pregnancy can mimic symptoms of congestive
      heart failure. Furthermore, many patients with valvular heart disease are first
      recognized during pregnancy. Pre-pregnancy intervention is of utmost importance
      in high-risk women who present for evaluation before a planned pregnancy. This is
      more so if the valvular lesion is amenable for percutaneous intervention or
      repair, without replacement. Besides management during the antepartal period,
      timing and mode of delivery should be decided upon jointly by the obstetrician,
      cardiologist, and obstetric anesthesiologist. Prosthetic mechanical valves which
      require anticoagulation present a high risk subset of patients. The American
      Heart Association/American College of Cardiology Task Force recommends continuous
      therapeutic anticoagulation with frequent monitoring. Warfarin and Heparin have
      been recommended. Low molecular weight heparin is not recommended to be
      administered to pregnant patients with mechanical prosthetic valves unless anti
      Xa levels are monitored 4 to 6 h after administration. Aspirin at low doses, 81
      325 mg has been proposed to reduce the risk of thrombosis. At this moment,
      optimal antithrombotic therapy in pregnant women with mechanical valves cannot be
      definitively recommended due to lack of properly designed studies.

PMID- 19400531
TI  - Cardiac manifestations of amyloid disease.
AB  - Amyloidosis has been defined as an infiltrative disorder primarily caused by
      extracellular tissue deposition of amyloid fibrils. There are at least twenty
      five different human and eight different animal proteins precursors of amyloid
      fibrils. Subtypes are differentiated by means of immunohistochemical and genetic
      testing, with prognosis and therapeutic strategies different from each other.
      There are a total of five types of amyloidosis: (1) Primary systemic amyloidosis,
      (2) secondary systemic amyloidosis, (3) Senile amyloidosis, (4) Hereditary
      amyloidosis, and (5) Hemodialysis-related. Cardiovascular manifestations can be
      fourfold and include congestive heart failure due to restrictive cardiomyopathy,
      vascular abnormalities, autonomic dysfunction, and conduction abnormalities.
      Tissue diagnosis remains the goal standard for diagnosis ofamyloidosis. Non
      invasive evaluation includes echocardiogram, cardiac MRI and Serum amyloid P
      component scintigraphy. These studies will be helpful in the diagnosis as well as
      follow up of patients with cardiac amyloidosis. Cardiac amyloidosis management
      will vary depending on the subtype but consist of supportive treatment of cardiac
      related symptoms and reducing the amyloid fibrils formation attacking the
      underlying disease.

PMID- 19400532
TI  - Benefits of risk factor modification through cardiac rehabilitation.
AB  - In the last few decades cardiac rehabilitation has evolved dramatically. It
      consists of a multidisciplinary approach for secondary prevention and
      rehabilitation treatment after an individual has sustained a cardiac event. A key
      principle for successful cardiac rehabilitation management is the modification of
      risk factors which have been demonstrated to have a significant impact on overall
      mortality and morbidity outcomes. This article summarizes some of the evidence
      that supports modification of risk factors through the use of cardiac
      rehabilitation.

PMID- 19400533
TI  - Left ventricular noncompaction/hypertrabeculation cardiomyopathy.
AB  - Two patients with the fascinating disorder of left ventricular noncompaction
      cardiomyopathy are reported and illustrated echocardiographically. A review of
      this increasingly recognized cardiomyopathy that may be accompanied by
      considerable morbidity and mortality, has been done.

PMID- 19400534
TI  - A case of Brugada syndrome in a 63 y/o man with chest pain.
AB  - Brugada syndrome (BS) is an under recognized condition inherited through
      autosomal dominant transmission that consists mainly of characteristic
      electrocardiogram findings with ST segment elevation, in leads V1 through V3,
      complemented with right bundle-branch block pattern. Patients usually have
      medical history of prior syncopal episodes and are at risk of sudden cardiac
      death; although diagnostic studies reveal structurally normal heart. Adequate
      treatment consists of implantable cardioverter defibrillator which can prevent
      associated lethal arrhythmias that lead to sudden cardiac death. Correct
      diagnosis with medical history and characteristic electrocardiographic findings
      is essential to the physician to prevent unnecessary treatments that can further
      compromise patient's health status.

PMID- 19400535
TI  - Recurrent syncope episodes in a 33-year-old male patient: case report and review
      of literature.
AB  - Case report and review of literature of a 33-year-old-male patient who was
      suffering from recurrent events of loss of consciousness (syncope) found to have
      multiple events of sustained and non sustained left bundle-branch morphology
      ventricular tachycardia during Holter evaluation. Both, the echocardiographic and
      magnetic resonance studies demonstrated morphological changes as seen in
      Arrhythmogenic right ventricular cardiomyopathy. Arrhythmogenic Right Ventricular
      Dysplasia (ARVD) is a rare cardiomyopathy characterized by life-threatening
      ventricular arrhythmias in the absence of apparent structural left heart disease,
      predominantly occurring within the male gender. Though it is mostly a hereditary
      condition, there are some sporadic cases. It is characterized by progressive
      degeneration and fibrous-fatty replacement of the right ventricular myocardium.
      The European Society of Cardiology and the International Society and Federation
      Task force is useful for the diagnosis of the condition because of the
      difficulties in as well as inaccuracies in tissue diagnosis. Patients with a
      diagnosis of ARVD who suffers from recurrent syncope events and ventricular
      arrhythmias an Implantable Cardiovertor-Defibrillator (ICD) is indicated to
      decrease their risk of sudden cardiac death events.

PMID- 19400536
TI  - Hurricanes, climate change and the cholera epidemic in Puerto Rico of 1855-1856.
AB  - Hurricanes and global climate changes may affect the environmental factors of
      cholera dynamics in warm coastal areas, vulnerable to seasonal or sporadic
      outbreaks. The cholera epidemic of Puerto Rico in 1855-1856 had a profound effect
      on the Puerto Rican society; but it was not influenced by any climatic events,
      such as preceding hurricanes or storms based on past documentary sources.
      Particularly, the environmental non-toxigenic strains of Vibrio Cholerae in
      Puerto Rican water sources can maintain their pathogenic potential for sporadic
      or erratic toxigenic cholera outbreaks--if a "perfect storm" ever occurs.

PMID- 19400537
TI  - Pitfalls of mapping a large Turkish consanguineous family with vertical
      monilethrix inheritance.
AB  - Monilethrix, a rare autosomal dominant disease characterized by hair fragility
      and follicular hyperkeratosis, is caused by mutations in three type II hair
      cortex keratins. The human keratin family comprises 54 members, 28 type I and 26
      type II. The phenotype shows variable penetrance and results in hair fragility
      and patchy dystrophic alopecia. In our study, Monilethrix was diagnosed on the
      basis of clinical characteristics and microscopic examination in a family with 11
      affected members. Haplotype analysis was performed by three Simple Tandem Repeat
      markers (STR) and KRT86 gene was sequenced for the identification of the disease
      causing mutation. In the results of this, autosomal dominant mutation (E402K) in
      exon 7 of KRT86 gene was identified as a cause of Moniltherix in the large family
      from Turkey.

PMID- 19400538
TI  - Deletion of Xpter encompassing the SHOX gene and PAR1 region in familial patients
      with Leri-Weill Dyschondrosteosis syndrome.
AB  - Heterozygote deletions or mutations of pseudoautosomal 1 region (PAR1)
      encompassing the short stature homeobox-containing (SHOX) gene cause Leri-Weill
      Dyschondrosteosis (LWD), which is a dominantly inherited osteochondroplasia
      characterized by short stature with mesomelic shortening of the upper and lower
      limbs and Madelung deformity of the wrists. SHOX is expressed by both sex
      chromosomes in males and females and plays an important role in bone growth and
      development. Clinically, the LWD expression is variable and more severe in
      females than males due to sex differences in oestrogen levels. Here, we report
      two familial cases of LWD with a large Xp terminal deletion (approximately 943
      kb) of distal PAR1 encompassing the SHOX gene. In addition, the proband had
      mental retardation which appeared to be from recessive inheritance in the family.

PMID- 19400539
TI  - A case of Bonneau syndrome associated with multiple renal cortical cysts.
AB  - We describe a 2-month-old girl with congenital anomalies including facial
      anomalies, complex cardiac anomalies, polysyndactyly, dysgenesis of distal
      extremities and bilateral multiple renal cysts. The proband was the child of
      first-cousin parents. Clinical synopsis in Bonneau syndrome (OMIM: 263630) is
      polysyndactyly and cardiac malformation. In addition, liver anomalies were
      reported in two patients. We discuss polysyndactyly and cardiac malformation with
      bilateral multiple renal cysts, a combination not reported previously.

PMID- 19400540
TI  - Central ray deficiency with extensive syndactyly: a dilemma for classification.
AB  - Split Hand Foot Malformation (SHFM) (cleft hand/foot, central ray deficiency) is
      a complex, highly variable anomaly involving the hands and/or feet. A clinical
      epidemiologic study of split hand/foot (central ray deficiency) of the Manitoba
      population identified a subset of patients who did not present with either
      typical or atypical split hand. Clinically, some patients presented with "mitten
      hand" syndactyly; the deficiency was not recognized before imaging. In this
      paper, we identify additional similarly affected literature cases, review
      existing classifications of split hand and syndactyly and attempt to classify
      these patients. This group presents a challenge for classification and genetic
      counseling. General classifications permit inclusion of patients with diverse
      phenotypes; however, details are overlooked. Osseous fusions and disorganization
      of osseous components complicate classification. Many of these patients had
      findings that overlapped different subtypes within existing classifications. This
      cohort highlights the importance of imaging patients with distal limb anomalies.
      An effective classification scheme should include relevant clinical and
      radiographic findings in order to assist clinicians following these patients.

PMID- 19400541
TI  - A novel duplication of chromosome (13)(q14.1q21.3) in a patient with mental
      retardation and microcephaly.
AB  - We report on a mentally retarded female with behavioural problems, microcephaly,
      mild facial dysmorphisms, short stature and small hands with thin fingers due to
      a de novo partial duplication within the long arm of chromosome 13(q14.1q21.3).
      She was primarily referred to the outpatient department of neuropsychiatry
      because of short lasting psychotic episodes. No formal psychiatric diagnosis was
      made and the behavioural problems appeared the result of anxieties provoked by
      novel situations, enhanced by the intellectual disability. To the author's
      knowledge, this duplication has not been published previously and it is
      considered causative of the phenotype.

PMID- 19400542
TI  - Mutations of the noggin (NOG) and of the activin A type I receptor (ACVR1) genes
      in a series of twenty-seven French fibrodysplasia ossificans progressiva (FOP)
      patients.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare but very severe disease,
      characterised by congenital malformations of the toes and by progressive
      heterotopic ossification of muscles and joints. Two genes, the noggin (NOG) gene
      and the activin A type I receptor (ACVRI) gene, are involved in FOP. In this
      study we have searched for the NOG and the 617G>A (ACVR1) mutations in a well
      characterized series of twenty-seven French FOP patients. Five NOG mutations
      (delta 42, 274G>C, 275G>A, 276G>A, and 283G>A) have been found in seven (26%) of
      our FOP patients. The 617G>A mutation in the ACVR1 gene is found in fourteen
      (52%) of the patients. With one exception (patient number 22), 617G>A and NOG
      mutations are mutually exclusive in patients. Mutations 274G>C, 283G>A and 617G>A
      segregate with the trait in five different FOP families, some members of them
      being partially affected by the disease.

PMID- 19400543
TI  - Frontonasal dysplasia: a family presenting autosomal dominant inheritance
      pattern.
AB  - Frontonasal dysplasia (FND, also called frontonasal dysostosis or median cleft
      face syndrome) includes a spectrum of abnormalities affecting the eyes, forehead
      and nose, and resulting from midfacial dysraphia. The clinical picture is highly
      variable, but major findings in FND include ocular hypertelorism, a broad nasal
      root, median cleft affecting nose or both the nose and upper lip, and widow's
      peak. It is usually a sporadic disorder, although a few familial cases have been
      reported. We report here a three-generation family with multiple affected members
      with frontonasal dysplasia. This observation suggests autosomal dominant
      inheritance. Furthermore, some of the features e.g. over-riding toes, nail
      changes, vertical crease on plantar region of the feet in the index patient were
      not reported up to now.

PMID- 19400544
TI  - The effect of a de novo pericentric inversion (10)(p11.1;q22.1) on aggressive
      behavior and hyperactivity.

PMID- 19400545
TI  - Intracardiac echogenic focus and cytogenetic abnormalities.

PMID- 19400546
TI  - A predictive method of calculating the dosimetric effect of 1-D motion on narrow
      multileaf collimated segments.
AB  - This study aims to investigate the utility of 1-D convolution as a predictive
      method to quantify the effect of patient movement as a result of respiration on
      segmented dose distributions typically found in IMRT. This is for the restricted
      case of 1-D motion perpendicular to the beam direction. A modified respiratory
      motion phantom was coupled to a solid water phantom and used to measure the dose
      distribution of several narrow MLC segments. The measured data was compared to
      dose distribution calculated by the mathematical convolution of static profiles
      with a probability distribution function (PDF) generated for sinusoidal motion
      and power cosine motion. The MLC segments for an IMRT field were also studied.
      Additionally, the dosimetric effect of intra-fraction patient motion combined
      with that of inter-fraction setup error, modelled using a Gaussian PDF, was
      calculated. Set-up variation and respiratory motion can significantly degrade the
      dose distribution of narrow segments. Our results emphasise the need to maintain
      the smallest feasible amplitude of respiratory motion and minimise set-up
      uncertainties, particularly when narrow segments are used.

PMID- 19400547
TI  - Issues encountered with kilovoltage x-ray reference dosimetry when changing codes
      of practice from TRS 277 to TRS 398.
AB  - A difference of 12% has been observed in the output of an 80 kV, 2.2 mm A1 HVL x
      ray beam when comparing measurements made according to the TRS 398 medium energy
      protocol with measurements made according to the TRS 277 low energy protocol.
      Absorbed dose to water chamber calibration factors used for the TRS 398
      measurements were derived from standards of air kerma with the use of the TRS 277
      medium energy protocol, and given this fact the discrepancy observed can be
      considered in terms of a difference between the TRS 277 low and medium energy
      protocols for this beam. Repeat measurements using the TRS 277 low and medium
      energy protocols have been made to confirm this. The most likely origins for the
      discrepancy observed are the chamber perturbation correction, p(u), obtained from
      TRS 277, and the value of the measured percentage depth dose at a depth of 2
      g.cm(-2) for this beam. Given these findings, reference dosimetry for this beam
      will be performed according to the TRS 398 low energy protocol.

PMID- 19400548
TI  - Energy dependence corrections to MOSFET dosimetric sensitivity.
AB  - Metal Oxide Semiconductor Field Effect Transistors (MOSFET's) are dosimeters
      which are now frequently utilized in radiotherapy treatment applications. An
      improved MOSFET, clinical semiconductor dosimetry system (CSDS) which utilizes
      improved packaging for the MOSFET device has been studied for energy dependence
      of sensitivity to x-ray radiation measurement. Energy dependence from 50 kVp to
      10 MV x-rays has been studied and found to vary by up to a factor of 3.2 with 75
      kVp producing the highest sensitivity response. The detectors average life span
      in high sensitivity mode is energy related and ranges from approximately 100 Gy
      for 75 kVp x-rays to approximately 300 Gy at 6 MV x-ray energy. The MOSFET
      detector has also been studied for sensitivity variations with integrated dose
      history. It was found to become less sensitive to radiation with age and the
      magnitude of this effect is dependant on radiation energy with lower energies
      producing a larger sensitivity reduction with integrated dose. The reduction in
      sensitivity is however approximated reproducibly by a slightly non linear, second
      order polynomial function allowing corrections to be made to readings to account
      for this effect to provide more accurate dose assessments both in phantom and in
      vivo.

PMID- 19400549
TI  - Evaluation of the magnitude of EBT Gafchromic film polarization effects.
AB  - Gafchromic EBT film, has become a main dosimetric tools for quantitative
      evaluation of radiation doses in radiation therapy application. One aspect of
      variability using EBT Gafchromic film is the magnitude of the orientation effect
      when analysing the film in landscape or portrait mode. This work has utilized a >
      99% plane polarized light source and a non-polarized diffuse light source to
      investigate the absolute magnitude of EBT Gafchromic films polarization or
      orientation effects. Results have shown that using a non-polarized light source
      produces a negligible orientation effect for EBT Gafchromic film and thus the
      angle of orientation is not important. However, the film exhibits a significant
      variation in transmitted optical density with angle of orientation to polarized
      light producing more than 100% increase, or over a doubling of measured OD for
      films irradiated with x-rays up to dose levels of 5 Gy. The maximum optical
      density was found to be in a plane at an angle of 14 degrees +/- 7 degrees (2 SD)
      when the polarizing sheet is turned clockwise with respect to the film. As the
      magnitude of the orientation effect follows a sinusoidal shape it becomes more
      critical for alignment accuracy of the film with respect to the polarizing
      direction in the anticlockwise direction as this will place the alignment of the
      polarizing axes on the steeper gradient section of the sinusoidal pattern. An
      average change of 4.5% per 5 degrees is seen for an anticlockwise polarizer
      rotation where as the effect is 1.2% per 5 degrees for an clockwise polarizer
      rotation. This may have consequences to the positional accuracy of placement of
      the EBT Gafchromic film on a scanner as even a 1 degree alignment error can cause
      an approximate 1% error in analysis. The magnitude of the orientation effect is
      therefore dependant on the degree of polarization of the scanning light source
      and can range from negligible (diffuse LED light source) through to more than
      100% or doubling of OD variation with a fully linear polarized light source.

PMID- 19400550
TI  - Evaluation of effective energy for QA and QC: measurement of half-value layer
      using radiochromic film density.
AB  - The effective energy of diagnostic X-rays is important for quality assurance (QA)
      and quality control (QC). However, the half-value layer (HVL), which is necessary
      to evaluate the effective energy, is not ubiquitously monitored because
      ionization-chamber dosimetry is time-consuming and complicated. To verify the
      applicability of GAFCHROMIC XR type R (GAF-R) film for HVL measurement as an
      alternative to monitoring with an ionization chamber, a single-strip method for
      measuring the HVL has been evaluated. Calibration curves of absorbed dose versus
      film density were generated using this single-strip method with GAF-R film, and
      the coefficient of determination (r2) of the straight-line approximation was
      evaluated. The HVLs (effective energies) estimated using the GAF-R film and an
      ionization chamber were compared. The coefficient of determination (r2) of the
      straight-line approximation obtained with the GAF-R film was more than 0.99. The
      effective energies (HVLs) evaluated using the GAF-R film and the ionization
      chamber were 43.25 keV (5.10 mm) and 39.86 keV (4.45 mm), respectively. The
      difference in the effective energies determined by the two methods was thus 8.5%.
      These results suggest that GAF-R might be used to evaluate the effective energy
      from the film-density growth without the need for ionization-chamber
      measurements.

PMID- 19400551
TI  - Neural correlates of alexithymia in response to emotional stimuli: a study of
      anorexia nervosa patients.
AB  - Individuals with alexithymia are typically unable to identify, understand, or
      describe their own emotions. Patients with anorexia nervosa (AN) have been shown
      to have high levels of alexithymia, and the latter trait may play an important
      role over the course of AN. However, relatively little is known about the
      underlying neurobiological relationships between alexithymia and AN. The aim of
      this study was to investigate the relationship between alexithymia level and
      brain activation in patients with AN. Thirty female patients participated in this
      study. Alexithymia was measured using the 20-item Toronto Alexithymia Scale.
      Functional magnetic resonance imaging was used to identify the brain regions that
      display abnormal hemodynamic activity while patients with AN were engaged in an
      emotional decision-making task. There was significant activation in the amygdala
      during the task, but not in the posterior and anterior cingulate cortices (PCC,
      ACC). However, PCC and ACC activation did vary as a function of alexithymia
      level. These results suggest that alexithymia in AN patients is associated with a
      deficit in the cognitive evaluation of negative emotions concerning body image.
      Alexithymia might play a crucial role in the emotional processing impairments
      that are often observed in AN patients, and this trait might ultimately help to
      better account for the psychopathological mechanism that underlies AN.

PMID- 19400552
TI  - Thiamylal and thiopental attenuate beta-adrenergic signaling pathway by
      suppressing adenylyl cyclase in rat ventricular myocytes.
AB  - The effects of intravenous anesthetics on myocytes have not been fully
      elucidated. To investigate the effects of various intravenous anesthetics such as
      fentanyl, morphine, ketamine, diazepam, midazolam, thiamylal, and thiopental on
      the beta-adrenergic signaling pathway, we measured isoproterenol-stimulated
      cyclic adenosine monophosphate (cAMP) production in freshly isolated rat
      ventricular myocytes. Fentanyl, morphine, ketamine, diazepam, and midazolam did
      not significantly affect isoproterenol-stimulated cAMP production. However,
      thiamylal and thiopental dose-dependently decreased cAMP production stimulated by
      isoproterenol or by forskolin, a direct adenylyl cyclase stimulator. In addition,
      we examined the role of protein kinase C (PKC) as a potential mediator of the
      thiamylal- or thiopental-induced effects on cAMP production using
      bisindolylmaleimide I, a non-specific PKC inhibitor. Bisindolylmaleimide I did
      not alter the inhibitory effects of thiamylal or thiopental. Thiamylal and
      thiopental significantly decreased isoproterenol-stimulated cAMP production by
      suppressing the adenylyl cyclase. We conclude that barbiturates such as thiamylal
      and thiopental decrease isoproterenol-stimulated cAMP production by suppressing
      the adenylyl cyclase through PKC-independent mechanisms.

PMID- 19400553
TI  - Differential diagnosis of hepatic tumor-like lesions in dog by using dynamic CT
      scanning.
AB  - Dynamic liver CT scanning is used to observe the hemodynamics of hepatic tumor
      like lesions by taking images sequentially after administration of contrast
      media. In this study in dogs, we compared the hemodynamic patterns of
      hepatocellular carcinoma (HCC), one of the malignant tumors, and nodular
      hyperplasia (NH), a benign tumor that is more common in older dogs. Thirty-six
      dogs with HCC and 40 dogs with NH, which were histopathologically diagnosed at
      Taniura Animal Hospital, were used as subjects. Dynamic CT scanning was performed
      and the data of each scanning phase were collected. Dilated blood vessels, septum
      formation, and capsule formation were noted in the tumors from 25, 17, and 25
      animals with HCC, respectively. In the arterial phase, high density and low
      contrast were noted in 8 and 23 dogs, respectively. Low density was noted in 34
      dogs in the equilibrium phase. In contrast, no dilated blood vessels, septum
      formation, or capsule formation was noted in the dogs with NH. High density, low
      contrast, and low density were noted in 8, 9, and 23 dogs, respectively, in the
      arterial phase. In the equilibrium phase, the enhancement level was equal to the
      surrounding liver tissues in all animals. The CT values of HCC in the plain, the
      arterial phase, portal venous phase and equilibrium phase after the
      administration of contrast media, were significantly (p < 0.05 to 0.001) lower
      than those of the surrounding liver tissues. In the arterial phase, the percent
      incidence of low density was significantly less in HCC than NH, while that of low
      contrast was significantly greater (p < 0.001) in HCC than NH. Dynamic CT
      scanning identified differences between the hemodynamics and internal structures
      of HCC and NH in dogs. Dynamic liver CT scanning can therefore be considered a
      useful technique in the differential diagnosis of hepatic tumor-like lesions in
      dogs.

PMID- 19400554
TI  - A cure Weibull gamma-frailty survival model and its application to exploring the
      prognosis factors of neuroblastoma.
AB  - The log rank test and the Cox regression, or modifications thereof, emphasize the
      effect of covariates on survival rate parameter. In some cases, cured
      individuals, i.e., individuals who may not experience the event of interest may
      exist in the population of interest. In this situation, we may wish to examine
      the effect of covariates on both survival rate and cured fraction parameters.
      Motivated by the Japanese neuroblastoma dataset, we consider a cure model that
      accounted for the effect of covariates on both of the abovementioned parameters.
      To deal with heterogeneity that is not explained by covariates, as well as
      individual random heterogeneity, we perform a frailty variable. Moreover, some
      nested models are fitted to deal with the principle of parsimony. The effect of
      covariates was then evaluated by the best nested model. From a statistical point
      of view, we found that the model of analysis is flexible and adequate to describe
      the abovementioned dataset. From a medical point of view, we confirmed AGE and
      STAGE to be the most dominant prognosis factor of neuroblastoma. We also conclude
      that NMYC and FERRITIN are the other most important prognosis factors. The
      analysis designated that some of the prognosis factors of neuroblastoma probably
      just affected the median life of patients and some others are the fatal prognosis
      factor indicated by their effect which significance on both of survival rate and
      cured fraction parameters. The present model of analysis is also potentially
      extendable to facilitate other aspects of inferences.

PMID- 19400555
TI  - Induction of gamma delta T cells using zoledronate plus interleukin-2 in patients
      with metastatic cancer.
AB  - A loss of human leukocyte antigen (HLA) expression in clinical tumors is one of
      their escape mechanisms from immune attack by HLA-restricted effector cells. In
      this study, the induction of HLA-unrestricted effector cells, gamma delta T
      cells, using zoledronate (ZOL) and interleukin (IL)-2 in vitro was investigated
      in patients with metastatic cancer. Peripheral blood mononuclear cells (PBMCs)
      from 10 cancer patients (8 colorectal and 2 esophageal) with multiple metastases
      and ascites lymphocytes from 3 cancer patients (1 gastric and 2 colorectal) were
      stimulated with varied concentrations of ZOL plus 100 U/ml IL-2 for 48 hr
      followed by culturing with IL-2 alone for 12 days. Lymphocyte proliferative
      responses were determined using 3H-TdR uptakes and interferon (IFN)-gamma
      production was evaluated using enzyme-linked immunosorbent assay. Surface
      phenotyping was performed using flow cytometry. Cytotoxic activity of effector
      cells was determined using 51Cr-releasing assay. It was found that proliferative
      responses of PBMCs were significantly stimulated with ZOL plus IL-2 when compared
      with IL-2 alone, showing 200 to 500-fold expansions for 2 weeks, although ZOL
      alone induced no response. The optimal concentration of ZOL was 1-5 microM.
      Ascites lymphocytes could also be stimulated with ZOL plus IL-2. The
      proliferative responses were remarkable in patients whose PBMCs could produce
      high levels of IFN-gamma during an initial 48-hr stimulation using ZOL plus IL-2.
      Removal of an adherent cell fraction before the induction augmented the
      proliferative responses in patients who otherwise had low-grade proliferative
      responses. Generated cells comprising approximately 90 or 20% in PBMCs from
      healthy donors or cancer patients, respectively, expressed gamma delta-type T
      cell receptor. Gamma delta T cells showed high cytotoxic activity against CD166
      positive TE12 and TE13 cancer cells but not against CD166-negative MKN45 cells.
      The cytotoxic activity against TE13 cells was augmented when target cells were
      pre-treated overnight with ZOL. These results suggest that ZOL in the presence of
      IL-2 can efficiently stimulate the proliferation of gamma delta T cells, which
      have cytotoxic properties against cancer cells. The use of zoledronate-activated
      killer (ZAK) cells should be encouraged in possible adoptive immunotherapy trials
      for patients with incurable cancer.

PMID- 19400556
TI  - Main pancreatic duct obstruction due to a small nonfunctioning endocrine tumor of
      the pancreas.
AB  - A 65-year-old Japanese male was referred to our hospital for evaluation of a main
      pancreatic duct obstruction. Two months previously, he had suffered an attack of
      acute pancreatitis that was resolved with conservative treatment. Dynamic
      contrast-enhanced study by multidetector row computed tomography revealed a well
      enhanced 5 x 5 mm mass in the head of the pancreas with dilatation of the main
      pancreatic duct in the body and tail. On endoscopic retrograde pancreatography,
      obstruction of the main pancreatic duct in the head of the pancreas was noted.
      Pancreatic juice cytology was nondiagnostic. Endoscopic ultrasonography
      demonstrated a well-defined hypoechoic mass, about 5 mm in size, with distal main
      pancreatic duct dilatation. The patient underwent elective pylorus-preserving
      pancreaticoduodenectomy. Pathological examination revealed a well-differentiated
      endocrine tumor of the pancreas of uncertain behavior, 5 mm in size.
      Immunohistochemically, the tumor was diffusely positive for chromogranin A and
      synaptophysin, and focally it was positive for insulin, glucagon, and CA19-9; it
      was negative for gastrin. The final diagnosis was main pancreatic duct
      obstruction secondary to a nonfunctioning endocrine tumor of the pancreas of
      uncertain behavior. Of note, a small nonfunctioning endocrine tumor of the
      pancreas is important in the differential diagnosis of main pancreatic duct
      obstruction demonstrated by radiographic examinations.

PMID- 19400557
TI  - Paramagnetic effects on the NMR spectra of "diamagnetic" ruthenium(bis
      phosphine)(bis-semiquinone) complexes.
AB  - Ligand substitution on cis-Ru(PPh(3))(2)(1,2-O(2)C(6)H(4))(2) gives cis
      RuL(1)L(2)(1,2-O(2)C(6)H(4))(2) (L(1) = PPh(3), L(2) = P(OPh)(3), PBu(3); L(1) =
      L(2) = PBu(3), P(OMe)(3)). Syntheses of cis-Ru(PPh(3))(2)(3,4-O(2)C(6)H(2)(5
      OH)CO(2)Me)(2) and cis-Ru(PPh(3))(2)(AGSQ)(2) (AGSQ = the semiquinone derived
      from 1,2,3-trihydroxyanthracene-9,10-dione) are also reported. The upfield
      chemical shifts and line broadening of the semiquinone 4,5-proton resonances in
      the NMR spectra indicate that these complexes, while having no detectable
      magnetic moments, have a weak, temperature-, ligand- and solvent-variable
      residual paramagnetism, not previously recognized in this series. Density
      functional theory (DFT) calculations predict a low-lying triplet state, about 14
      kJ/mol (0.15 eV) above the singlet ground state. The paramagnetic effects on the
      NMR spectra are attributed to singlet-triplet equilibria. Temperature dependence
      of the proton resonances of the semiquinone rings of cis-Ru(PPh(3))(2)(1,2
      O(2)C(6)H(4))(2) was used to calculate the singlet-triplet free energy difference
      as 17.5-18.0 kJ/mol in toluene.

PMID- 19400558
TI  - Fluxionality in a paramagnetic seven-coordinate iron(II) complex: a variable
      temperature, two-dimensional NMR and DFT study.
AB  - The preparation and detailed characterizations of the high-spin seven-coordinate
      complexes [M(kappa(7)N-L)](ClO(4))(2) (M = Mn(II), Fe(II); L = N,N,N',N'
      tetrakis(2-pyridylmethyl)-2,6-bis(aminomethyl)pyridine) are described. The X-ray
      crystal structures reveal seven-coordinate metal complex ions. Consideration of
      continuous shape measures reveals that the coordination environments about the
      metal ions are better described as having (C(s)) face-capped trigonal prismatic
      symmetry than (C(2)) pentagonal bipyramidal symmetry. The (S = (5)/(2)) Mn(II)
      species shows complicated X-band electron paramagnetic resonance (EPR) spectra
      and broad, unrevealing (1)H NMR spectra. In contrast, the (S = 2) Fe(II) complex
      is EPR-silent and shows completely interpretable (1)H NMR spectra containing the
      requisite number of paramagnetically shifted peaks in the range delta +150 to 
      60. The (13)C NMR spectra are likewise informative. Variable-temperature (1)H NMR
      spectra show coalescences and decoalescences indicative of an intramolecular
      process that pairwise-exchanges the nonequivalent pyridylmethyl "arms" of the two
      bis(pyridylmethyl)amine (bpa) domains. A suite of NMR techniques, including T(1)
      relaxation measurements and variable-temperature (1)H-(1)H correlation
      spectroscopy, (1)H-(1)H total correlation spectroscopy, (1)H-(1)H nuclear
      Overhauser effect spectroscopy/exchange spectroscopy, and (1)H-(13)C
      heteronuclear multiple-quantum coherence experiments, has been used to assign the
      NMR spectra and characterize the exchange process. Analysis of the data from
      these experiments yields the following thermodynamic parameters for the exchange:
      DeltaH++ = 53.6 +/- 2.8 kJ mol(-1), DeltaS++ = -10.0 +/- 9.8 J K(-1) mol(-1), and
      DeltaG++ (298 K) = 50.6 kJ mol(-1). Density functional theory (B3LYP)
      calculations have been used to explore the energetics of possible mechanistic
      pathways for the underlying fluxional process. The most plausible mechanism found
      involves dissociation of a pyridylmethyl arm to afford a strained six-coordinate
      species followed by rebinding of the arm in a different position to afford a new
      seven-coordinate transition state in which the pyridylmethyl arms within each bpa
      domain are essentially equivalent; the calculated energy barrier for this process
      is 53.5 kJ mol(-1), in good agreement with the observations.

PMID- 19400559
TI  - Syntheses and crystal structures of ruthenium and rhodium olefin complexes
      containing GaCp.
AB  - The reactivity of olefin containing complexes of the d(8) metals Ru(0) and Rh(I)
      toward GaCp* and AlCp* is presented. [Ru(eta(4)-butadiene)(PPh(3))(3)] reacts
      with GaCp* to give the substitution product [Ru(eta(4)
      butadiene)(PPh(3))(2)(GaCp*)] (1), which proved to be stable in the presence of
      GaCp* even under hydrogenolytic conditions. In contrast, the bis-styrene complex
      [Ru(PPh(3))(2)(styrene)(2)] undergoes full substitution of the olefin ligands to
      give [Ru(PPh(3))(2)(GaCp*)(3)] (2), whereas reaction of [Ru(eta(2),eta(2)
      COD)(eta(6)-COT)] (COD = 1,5-cyclooctadiene, C(8)H(12), COT = 1,3,5
      cyclooctatriene, C(8)H(10)) and GaCp* leads to [Ru(eta(2),eta(2)-COD)(GaCp*)(3)]
      (3) under mild hydrogenolytic conditions. Analogously, the Rh(I) compounds
      [{Rh(eta(2),eta(2)-NBD)(PCy(3))(2)}{BAr(F)}] (NBD = norbornadiene) and
      [{Rh(eta(2),eta(2)-COD)(2)}{BAr(F)}] ({BAr(F)}= B{[C(6)H(3)(CF(3))(2)](4)) yield
      the complexes [{Rh(eta(2),eta(2)-NBD)(PCy(3))(GaCp*)(2)}{BAr(F)}] (4),
      [{Rh(eta(2),eta(2)-COD)(GaCp*)(3)}{BAr(F)}] (5), and [{Rh(eta(2),eta(2)
      COD)(AlCp*)(3)}{BAr(F)]}] (6) upon reaction with the appropriate ECp* ligand (E =
      Al, Ga). All new complexes have been characterized by means of (1)H and (13)C NMR
      spectroscopy and elemental analysis, as well as X-ray single crystal structure
      analysis in the case of 1-5.

PMID- 19400561
TI  - Synthesis and structural characterization of five-coordinate aluminum complexes
      containing diarylamido diphosphine ligands.
AB  - A series of five-coordinate aluminum complexes supported by o-phenylene-derived
      amido diphosphine ligands, [N(o-C(6)H(4)PR(2))(2)](-) ([R-PNP](-); R = Ph, (i)Pr)
      and [N(o-C(6)H(4)PPh(2))(o-C(6)H(4)P(i)Pr(2))](-) ([Ph-PNP-(i)Pr](-)), have been
      prepared and structurally characterized. Alkane elimination reactions of
      trialkylaluminum with H[Ph-PNP] (1a), H[(i)Pr-PNP] (1b), and H[Ph-PNP-(i)Pr] (1c)
      in toluene at -35 degrees C respectively produced the corresponding dialkyl
      complexes [Ph-PNP]AlR(2), [(i)Pr-PNP]AlR(2), and [Ph-PNP-(i)Pr]AlR(2) (R = Me (2a
      c), Et (3a-c), (i)Bu (4a-c)) in high isolated yield. The dihydride complexes [Ph
      PNP]AlH(2) (6a), [(i)Pr- PNP]AlH(2) (6b), and [Ph-PNP-(i)Pr]AlH(2) (6c) were
      prepared in one-pot reactions of in situ prepared dichloride precursors (5a-c)
      with LiAlH(4) in THF at room temperature. X-ray diffraction studies of 2a-c, 3b
      c, 5b, and 6b revealed a distorted trigonal-bipyramidal structure for these
      molecules in which the two phosphorus donors are mutually trans. The solution
      structures of these organoaluminum complexes were all characterized by (1)H,
      (13)C, and (31)P NMR spectroscopy. The NMR data are indicative of solution C(2)
      symmetry for [Ph-PNP](-) and [(i)Pr-PNP](-) complexes, whereas they are
      indicative of C(1) for [Ph-PNP-(i)Pr](-) derivatives. The (1)H NMR spectra of 3a
      c and 4a-c revealed diastereotopy for the alpha-hydrogen atoms in these
      molecules.

PMID- 19400560
TI  - Blue-, green- and non-luminescent crystals from one reaction. Isolation and
      structural characterization of a series of gold(I)-silver(I) heterometallic
      complexes utilizing a gold carbene metalloligand containing free amino groups.
AB  - The metalloligand [Au{C(NHMe)(NHCH(2)CH(2)NH(2))}(2)]Cl, 1, has been prepared by
      the reaction of ethylenediamine with [Au(CNMe)(2)]Cl. Compound 1 crystallized as
      a luminescent dimer with a Au...Au separation of 3.0224(4) A. It reacted in
      solution with silver hexafluorophosphate to form the coordination polymer,
      {[Au{mu-C(NHMe)(NHCH(2)CH(2)NH(2))}(2)Ag(NCMe)](PF(6))(2)}(n), 2. The structure
      of 2 involves a chain of alternating gold(I) and silver(I) ions with a Au...Ag
      distance of 2.9694(4)A. The reaction of the metalloligand, 1, with silver
      tetrafluoroborate yielded three products: the green luminescent coordination
      polymer, {[Au{mu-C(NHMe)(NHCH(2)CH(2)NH(2))}(2)Ag-(NCMe)](BF(4))(2)}(n), 3, which
      is analogous to 2; the non-luminescent binuclear complex, [Au{mu
      C(NHMe)(NHCH(2)CH(2)NH(2))}(2)Ag](BF(4))(2), 4; and the blue luminescent complex,
      [{mu-C(NHMe)NHCH(2)CH(2)NH(MeHN)C}Au(2){mu
      C(NHMe)(NHCH(2)CH(2)NH(2))}(2)Ag](BF(4))(3-) x 3(MeCN), 5. Compound 5 involves a
      bent Au...Ag...Au cation with two different Au...Ag distances (2.9165(8) A and
      3.1743(8) A). This cation self-associates through a Au...Au interaction of
      3.0275(5) A, which allows the formation of an extended zigzag chain of cations in
      5.

PMID- 19400562
TI  - Hydrothermal syntheses and characterizations of thioarsenates [Fe(phen)3][As3S6]
      x dien x 7 H2O and [Mn2(phen)4(As2S5)] x phen x 2 H2O: a new coordination mode of
      the As2S5(4-) anion.
AB  - Novel hydrogen-bonded supramolecular thioarsenates [Fe(phen)(3)][As(3)S(6)] x
      dien x 7 H(2)O (1) and [Mn(2)(phen)(4)(As(2)S(5))] x phen x 2 H(2)O (2) (dien =
      diethylenetriamine, phen = 1,10-phenanthroline) were hydrothermally synthesized
      and characterized. The structure of 1 consists of [As(3)S(6)](3-)-H(2)O anionic
      layers and [Fe(phen)(3)](3+)-dien cationic layers assembled via O-H...S and O
      H...N hydrogen-bonding interactions. The layers stack alternately and are
      parallel to each other to give a 3D network structure with channels accommodating
      unique branched water chains, which are anchored on the anionic and cationic
      layers via hydrogen bonds. In 2, the [As(2)S(5)](4-) anion acts as a tetradentate
      brigding ligand via four terminal S atoms to link two [Mn(phen)(2)](2+) cations,
      forming the neutral complex [Mn(2)(phen)(4)(As(2)S(5))]. This is a new
      coordination mode for the [As(2)S(5)](4-) ion. [Mn(2)(phen)(4)(As(2)S(5))], phen,
      and H(2)O form a 3D network structure via O-H...S, O-H...O, and pi-pi stacking
      interactions.

PMID- 19400563
TI  - Mixed f-d coordination complexes as dual visible- and near-infrared-emitting
      probes for targeting DNA.
AB  - A new family of mixed-lanthanide (Yb(III) and Nd(III)) transition-metal (f-d)
      cyclen-Ru(II)(phen)(3) (phen = 1,10-phenanthroline) complexes were synthesized as
      dual visible- and near-infrared (NIR)-emitting DNA probes/sensors. Significant
      changes were seen in both the Ru(II) visible and the Yb(III)-centered NIR
      emission, which was switched off upon binding to DNA at pH 7.4. In contrast, no
      changes were seen in the Nd(III) emission of the analogue f-d conjugate.

PMID- 19400564
TI  - Ligand-assisted preparation of palladium supported nanoparticles: a step toward
      size control.
AB  - Supported nanoparticles (SNPs) with narrow size distribution were prepared by
      H(2) reduction of Pd(2+) previously bound to ligand-modified silica surfaces.
      Interestingly, the size of the Pd(0) SNPs was tuned by the ligand grafted on the
      support surface. Amino- and ethylenediamino-functionalized supports formed Pd(0)
      SNPs of ca. 6 and 1 nm, respectively. The catalytic properties of both Pd(0) SNPs
      were investigated.

PMID- 19400565
TI  - Small-molecule diffusion through polycrystalline triglyceride networks quantified
      using fluorescence recovery after photobleaching.
AB  - Fluorescence recovery after photobleaching (FRAP) has been used to quantify Nile
      red diffusion through five different triglyceride crystal networks composed of
      pure peanut oil (PeO), pure chemically interesterified fully hydrogenated palm
      oil (IHPO), two blends of PeO and IHPO blended in different mass ratios (70:30
      and 30:70%, w/w), and pure cocoa butter. Calculated components from FRAP
      experiments (effective diffusion coefficient (D(eff)) and mobile fraction (Mr))
      were correlated with crystal network structural characteristics (crystalline mass
      fraction and permeability coefficient) and illustrated that D(eff) can be
      predicted using this tool. Higher-permeability coefficients found for higher
      fractal dimensions, lower volume fraction of solids, and larger average particle
      sizes were significantly correlated to higher D(eff).

PMID- 19400567
TI  - Determination of the electron escape depth for NEXAFS spectroscopy.
AB  - A novel method was developed to determine carbon atom density as a function of
      depth by analyzing the postedge signal in near-edge X-ray absorption fine
      structure (NEXAFS) spectra. We show that the common assumption in the analysis of
      NEXAFS data from polymer films, namely, that the carbon atom density is constant
      as a function of depth, is not valid. This analysis method is then used to
      calculate the electron escape depth (EED) for NEXAFS in a model bilayer system
      that contains a perfluorinated polyether (PFPE) on top of a highly oriented
      pyrolitic graphite (HOPG) sample. Because the carbon atom densitites of both
      layers are known, in addition to the PFPE surface layer thickness, the EED is
      determined to be 1.95 nm. This EED is then used to measure the thickness of the
      perfluorinated surface layer of poly(4-(1H,1H,2H,2H
      perfluorodecyl)oxymethylstyrene) (PFPS).

PMID- 19400566
TI  - Surface properties and conformation of Nephila clavipes spider recombinant silk
      proteins at the air-water interface.
AB  - The dragline fiber of spiders is composed of two proteins, the major ampullate
      spidroins I and II (MaSpI and MaSpII). To better understand the assembly
      mechanism and the properties of these proteins, the adsorption behavior of the
      recombinant proteins of the spider Nephila clavipes produced by Nexia
      Biotechnologies Inc. has been studied at the air-water interface using
      ellipsometry, surface pressure, rheological, and infrared measurements. The
      results show that the adsorption is more rapid and more molecules are present at
      the interface for MaSpII than for MaSpI. MaSpII has thus a higher affinity for
      the interface than MaSpI, which is consistent with its higher aggregation
      propensity in water. The films formed at the interface consist of networks
      containing a high content of intermolecular beta-sheets as revealed by the in
      situ polarization modulation infrared absorption reflection spectra. The infrared
      results further demonstrate that, for MaSpI, the beta-sheets are formed as soon
      as the proteins adsorb to the interface while for MaSpII the beta-sheet formation
      occurs more slowly. The amount of beta-sheets is lower for MaSpII than for MaSpI,
      most likely due to the presence of proline residues in its sequence. Both
      proteins form elastic films, but they are heterogeneous for MaSpI and homogeneous
      for MaSpII most probably as a result of a more ordered and slower aggregation
      process for MaSpII. This difference in their mechanism of assembly and
      interfacial behaviors does not seem to arise from their overall hydrophobicity or
      from a specific pattern of hydrophobicity, but rather from the longer polyalanine
      motifs, lower glycine content, and higher proline content of MaSpII. The
      propensity of both spidroins to form beta-sheets, especially the polyalanine
      blocks, suggests the participation of both proteins in the silk's beta-sheet
      crystallites.

PMID- 19400568
TI  - Highly sensitive and selective label-free optical detection of DNA hybridization
      based on photon upconverting nanoparticles.
AB  - We report a label-free optical detection scheme for DNA hybridization using
      photon upconverting nanoparticles. On the basis of luminescence resonance energy
      transfer between a donor and an acceptor, the method is highly sensitive and can
      differentiate targets with single base variation. Photon upconverting
      nanoparticles were used as the donor and an intercalating dye as the acceptor.
      The sensor could differentiate the perfectly matched target from the single-base
      mismatched target. The detection limit of this sensor toward perfectly matched
      target was calculated to be 20 fmol, with no photobleaching. Oligonucleotide
      sensors of such design demonstrate high sensitivity and specificity without
      fluorophore labeling.

PMID- 19400570
TI  - Thermodynamic modeling of promoted structure II clathrate hydrates of hydrogen.
AB  - This work presents a thermodynamic model of equilibrium states of binary
      structure II gas hydrates of hydrogen with different promoters based on the van
      der Waals-Platteeuw statistical thermodynamic model. Since the determination of
      the occupancy of the small cavities by hydrogen is still an unresolved question,
      the model allows for multiple occupancy of these cavities. The agreement of the
      predictions of the model with experimental data is satisfactory, with average
      absolute pressure deviations below 10%. Model results indicate that at the
      pressures of hydrogen hydrate formation, the small cavities of the hydrate are
      singly occupied by hydrogen and that at moderate pressures (P<30 MPa), hydrogen
      hardly displaces the promoter from the large cavities, even when the
      concentration of the promoter is reduced below the stoichiometric concentration.
      Model results are also used to optimize the conditions for hydrogen storage in
      the gas hydrates.

PMID- 19400569
TI  - Silver(I)-catalyzed cascade: direct access to furans from alkynyloxiranes.
AB  - Functionalized furans are conveniently formed by a new silver(I)-catalyzed
      reaction of alk-1-ynyl oxiranes in the presence of p-toluenesulfonic acid and
      methanol. Evidence supported a cascade mechanism.

PMID- 19400571
TI  - Conformation-specific pathways of beta-alanine: a vacuum ultraviolet
      photoionization and theoretical study.
AB  - We report a photoionization and dissociative photoionization study of beta
      alanine using IR laser desorption combined with synchrotron vacuum ultraviolet
      (VUV) photoionization mass spectrometry. Fragments at m/z = 45, 44, 43, and 30
      yielded from photoionization are assigned to NH(3)CH(2)CH(2)(+), NH(2)CHCH(3)(+),
      NH(2)CHCH(2)(+), and NH(2)CH(2)(+), respectively. Some new conformation-specific
      dissociation channels and corresponding dissociation energies for the observed
      fragments are established and determined with the help of ab initio G3B3
      calculations and measurements of photoionization efficiency (PIE) spectra. The
      theoretical values are in fair agreement with the experimental results. Three low
      lying conformers of the beta-alanine cation, including two gauche conformers G1+,
      G2+ and one anti conformer A+ are investigated by G3B3 calculations. The
      conformer G1+ (intramolecular hydrogen bonding N-H...OC) is found to be another
      precursor in forming the NH(3)CH(2)CH(2)(+) ion, which is complementary to the
      previously reported formation pathway that only occurs with the conformer G2+
      (intramolecular hydrogen bonding O-H...N). Species NH(2)CHCH(2)(+) may come from
      the contributions of G1+, G2+, and A+ via different dissociation pathways. The
      most abundant fragment ion, NH(2)CH(2)(+), is formed from a direct C-C bond
      cleavage. Intramolecular hydrogen transfer processes dominate most of the
      fragmentation pathways of the beta-alanine cation.

PMID- 19400572
TI  - Blue light emitting Ir(III) compounds for OLEDs - new insights into ancillary
      ligand effects on the emitting triplet state.
AB  - The sky-blue emitting phosphorescent compound Ir(4,6-dFppy)(2)(acac) (FIracac)
      doped into different matrices is studied under ambient conditions and at
      cryogenic temperatures on the basis of broadband and high-resolution emission
      spectra. The emitting triplet state is found to be largely of metal-to-ligand
      charge transfer (MLCT) character. It is observed that different polycrystalline
      and amorphous hosts distinctly affect the properties of the triplet. Moreover, a
      comparison of FIracac with the related Ir(4,6-dFppy)(2)(pic) (FIrpic), differing
      only by the ancillary ligand, reveals obvious changes of properties of the
      emitting state. These observations are explained by different effects of acac and
      pic on the Ir(III) d-orbitals. In particular, the occupied frontier orbitals,
      strongly involving the t(2g)-manifold, and their splitting patterns are modified
      differently. This influences spin-orbit coupling (SOC) of the emitting triplet
      state to higher-lying (1,3)MLCT states. As a consequence, zero-field splittings,
      radiative decay rates, and phosphorescence quantum yields are changed. The
      important effects of SOC are discussed qualitatively and are related to the
      emission properties of the individual triplet substates, as determined from
      highly resolved spectra. The results allow us to gain a better understanding of
      the impact of SOC on the emission properties with the aim to develop more
      efficient triplet emitters for OLEDs.

PMID- 19400573
TI  - Cationic comb polymer superdispersants for colloidal silica suspensions.
AB  - We investigate the ability of a cationic comb polymer composed of a
      poly(trimethylammonium iodide ethyl methacrylate) (PTMAM) backbone and uncharged
      poly(ethylene glycol) (PEG) teeth to stabilize aqueous silica suspensions of
      varying ionic strength and pH. Both PTMAM-g-PEG and its homopolymer backbone,
      PTMAM, are synthesized via reversible addition-fragmentation chain transfer
      followed by quaternization of the pendant amine groups with methyl iodide.
      Through a combination of polymer adsorption, zeta potential, and sedimentation
      measurements as well as confocal imaging of sediment structures, we find that
      PTMAM-g-PEG imparts stability over a broad range of solution conditions, where
      pure PTMAM fails.

PMID- 19400574
TI  - Investigation of low-lying states of oxygen molecule via second-order
      multireference perturbation theory: a state-specific approach.
AB  - The relative performance of four variants of the Moller-Plesset (MP) partitioning
      (using different diagonal one-electron unperturbed Hamiltonian, H0) based state
      specific multireference perturbation theory (SS-MRPT) [termed as SS-MRPT(MP)] has
      been investigated and demonstrated by calculations of the dissociation potential
      energy curves (PECs) of the first three electronic states [ground state X3Sigmag-
      as well as low-lying singlet excited states, a1Deltag and b1Sigmag+] of the
      oxygen molecule using different basis sets. The spectroscopic constants extracted
      from the computed PECs obtained by the SS-MRPT(MP) method are calibrated with
      respect to the corresponding value of the full configuration interaction (FCI)
      and experimental data for the corresponding states. We have also computed
      vertical excitation (or transition) energies and compared those with the
      corresponding FCI values along with the results of other available sophisticated
      methods. Encouraging agreement between SS-MRPT(MP) theory and some benchmark
      calculations has been observed. We have thus assessed the applicability and
      accuracy of the SS-MRPT(MP) method with different diagonal one-electron
      partitioning schemes. The ability of the SS-MRPT(MP) method with different
      partitioning schemes to predict full PECs and spectroscopic constants of the
      ground state and excited states with almost equivalent accuracy is promising.

PMID- 19400577
TI  - Theoretical analysis of bonding in N-heterocyclic carbene-rhodium complexes.
AB  - The natural orbitals for chemical valence and the Ziegler-Rauk bond energy
      decomposition analysis were used to describe the donor/acceptor character of the
      N-heterocyclic carbenes (NHC)-metal bond in two groups of square-planar
      rhodium(I) complexes: (NHC)RhCl(cod) (1-X; cod = 1,5-cyclooctadiene) and
      (NHC)RhCl(CO)(2) (2-X), with a group X = H, Cl, NO(2), or CN located on the NHC
      ligand. The results show that the NHC-metal bond consists of the components
      originating from donation (sigma symmetry) and back-donation (two contributions
      of the pi symmetry, out-of-plane and in-plane, accompanied by one sigma-back
      bonding component). The charge-flow measures from NOCV indicate that the total
      back-bonding contribution is of comparable importance to donation. The out-of
      plane pi component contributes to ca. 50% of the total back-bonding charge-flow.
      The energy measures from the Ziegler-Rauk analysis show that the total back
      bonding energy corresponds to ca. 40% of the orbital interaction energy. The
      ligand trans to NHC (CO or cod) strongly affects the back-bonding component; for
      the complexes 1-X, the back-donation is substantially enhanced compared to 2-X.
      The back-bonding component increases with an increase in the pi-withdrawing
      ability of X for both, 1-X and 2-X. However, this effect is relatively small.
      Back-bonding components of the two bonds involving the metal are strongly
      coupled; an increase in NHC-Rh leads to a decrease in Rh-olefin/CO(trans). The
      changes in the back-bonding are too small to be followed by the trends in bond
      energies, which are finally determined by the electrostatic and Pauli repulsion
      energy.

PMID- 19400575
TI  - Organometallic [Re(CO)3]+ and [Re(CO)2(NO)]2+ labeled substrates for human
      thymidine kinase 1.
AB  - Thymidine was functionalized at position N3 with a tridentate iminodiacetic acid
      chelating system and a potentially tetradentate mercaptoethyliminodiacetic acid
      chelating system. Spacers of different lengths (ethyl and butyl) were introduced
      between the chelators and thymidine. The derivatives were labeled with the
      [Re(CO)(2)(NO)](2+) and [Re(CO)(3)](+) cores to give isostructural complexes with
      different overall charges. All complexes were analyzed by NMR, MS, and IR, and in
      addition, the X-ray structure of a [Re(CO)(2)(NO)](2+) labeled thymidine
      derivative functionalized at the N3 position was solved. The ligands
      incorporating the potentially tetradentate mercaptoethyliminodiacetic acid
      chelating system coordinated tridentately through iminodiacetic acid to both the
      [Re(CO)(2)(NO)](2+) core and the [Re(CO)(3)](+) core. This was surprising given
      that the reaction of [NEt(4)][Re(CO)(2)(NO)Br(3)] with the model ligand
      ethylmercaptoethyliminodiacetic acid led to dissociation of a carbonyl ligand and
      formation of a monocarbonyl-mononitrosyl complex, as confirmed by X-ray structure
      analysis. All of the organometallic thymidine derivatives were substrates for
      human thymidine kinase 1, a key enzyme in (cancer) cell proliferation. Neutral
      [Re(CO)(2)(NO)](2+) labeled thymidine derivatives revealed substrate activity
      ranging from 24 to 40%, and the structurally analogous anionic [Re(CO)(3)](+)
      labeled thymidine derivatives from 20 to 38% compared with the natural substrate
      thymidine.

PMID- 19400576
TI  - Molecular voids formed from effective attraction in submonolayer DNA deposited on
      Au(111).
AB  - The development of DNA-based biosensors requires a deep understanding of how DNA
      molecules adsorb and organize on solid state surfaces as well as the electronic
      properties of individual and aggregates of DNA molecules. Using scanning
      tunneling microscopy (STM) and atomic force microscopy (AFM), we have
      successfully characterized an attractive force driven molecular void formation
      for DNA chemically adsorbed on Au(111) as a function of strand length and
      deposition conditions. Here we report the observation of these void structures
      formed on the Au(111) surface by adsorption of both 45 and 90 base pair long,
      thiolated double-stranded DNA. We found that the average void diameter decreases
      when increasing the number of base pairs exposed to the surface. The critical
      determinant in the molecular void formation is the total charge delivered to the
      surface via the adsorption of the DNA strands and the related counterions, which
      can ultimately be quantified by the number of base pairs in each adsorbed DNA
      molecule. Complementary measurements involving STM and AFM suggest that an intact
      Au(111) surface area is preserved inside the void and is surrounded by a
      submonolayer of DNA molecules adsorbed on the surface. The discussion of the
      possible mechanisms for the void formation implies an effective attraction
      between the DNA molecules.

PMID- 19400579
TI  - Nanoscale reversible mass transport for archival memory.
AB  - We report on a simple electromechanical memory device in which an iron
      nanoparticle shuttle is controllably positioned within a hollow nanotube channel.
      The shuttle can be moved reversibly via an electrical write signal and can be
      positioned with nanoscale precision. The position of the shuttle can be read out
      directly via a blind resistance read measurement, allowing application as a
      nonvolatile memory element with potentially hundreds of memory states per device.
      The shuttle memory has application for archival storage, with information density
      as high as 10(12) bits/in(2), and thermodynamic stability in excess of one
      billion years.

PMID- 19400578
TI  - Protective antigen detection using horizontally stacked hexagonal ZnO platelets.
AB  - Anthrax toxin detection before bacteremia, when toxin concentration is low,
      improves the chances of efficient treatment and cure. We present a novel
      technique for ultrasensitive detection of a protective antigen (PA(83)) of
      anthrax using an array of zinc oxide nanorods in conjunction with a FITC-labeled
      PA affinity peptide. The nanorods are composed of horizontally stacked hexagonal
      platelets which are uniformly spaced and grown unidirectionally upon a glass
      substrate via a new and simple technique. Images taken under UV emission
      demonstrate fluorescence sensitivity to PA as a function of antigen
      concentration, and a negative control using bovine serum albumin produced no
      fluorescence signal. The fluorescence signal of the PA-peptide complex is also
      significantly reduced in the absence of the nanorods, suggesting that the
      presence of ZnO nanorods inhibits the self-quenching properties of the
      fluorophore. A lower limit of detection for the assay system for PA is estimated
      at 150 aM, which demonstrates the possibility of using ZnO nanorods in biological
      sensor systems.

PMID- 19400580
TI  - Gold(I)-catalyzed intermolecular hydroalkoxylation of allenes: a DFT study.
AB  - The mechanistic and regiochemical aspects in the Au(I)-catalyzed intermolecular
      hydroalkoxylation of allenes have been studied computationally. The most
      favorable pathway is nucleophilic attack of an Au(I)-coordinated allene, which
      occurs irreversibly. An Au(I)-catalyzed mechanism is proposed that allows the
      facile interconversion of regioisomeric allylic ether products. The regioisomers
      are connected via a stabilized diether intermediate with a C-Au sigma-bond, which
      successfully explains the observed regioselectivity for the thermodynamic
      product.

PMID- 19400581
TI  - Hierarchically nanostructured rutile arrays: acid vapor oxidation growth and
      tunable morphologies.
AB  - A general acid vapor oxidation (AVO) strategy has been developed to grow highly
      oriented hierarchically structured rutile TiO(2) nanoarrays with tunable
      morphologies from titanium thin films. This is a simple one-pot synthesis
      approach involving the reaction of a titanium surface with the vapor generated
      from a hydrochloric acid solution in a Teflon lined autoclave. To the best of our
      knowledge, this is the first successful attempt to grow ordered tree-like titania
      nanoarrays. A possible formation mechanism for the interesting architectures has
      been proposed based on series of time-dependent experiments. By adjusting the
      initial HCl concentration, films of different rutile structures including
      nanotrees, dendritic nanobundles, and nanorods can be selectively obtained.
      Subsequently, the surface morphologies and wettability can be readily tuned.

PMID- 19400582
TI  - Global quantitative proteomic profiling through 18O-labeling in combination with
      MS/MS spectra analysis.
AB  - Several stable-isotope-based peptide labeling methods have been developed to
      support large-scale relative quantitation, through mass spectrometry, of proteins
      present in two different biological samples. In one of these, trypsin-catalyzed
      18O-based labeling, quantitation is typically performed at the full scan (MS)
      level by comparing the peak intensities of sister precursor ions corresponding to
      the labeled and unlabeled forms of an intact peptide as they co-elute during
      liquid chromatography (LC) separations. We show here that measuring relative
      abundance at the product ion (MS/MS) level after fragmentation provides excellent
      accuracy, sensitivity and signal-to-noise, while combining quantitation with
      global shotgun protein identification. To facilitate routine data analysis using
      this approach, we have developed two specialized software programs, ySelect and
      yRatios, which draw upon database search results for 18O-based data sets and
      combine fragmentation spectra peak lists to (1) accurately determine protein
      ratios between two samples while applying a correction for incomplete labeling
      and (2) tabulate these results in both intuitive summary reports and in formats
      amenable to systematic pathway level analysis. To validate our process, we
      subjected simple and complex test protein mixtures to single-step and multistep
      LC-MS/MS profiling experiments. Ratio distributions approached the expected
      means, allowing empirical derivation of confidence level cutoffs for determining
      statistically significant fold-changes in protein abundance. A set of stringent
      criteria for detecting spurious ratios based on consistency checking between
      unlabeled and labeled y-ion pairs was found to highlight putative false positive
      identifications. In summary, this toolkit facilitates comparative proteomic
      quantitation under conditions that are optimized for making reliable protein
      inferences.

PMID- 19400583
TI  - Cations modulate polysaccharide structure to determine FGF-FGFR signaling: a
      comparison of signaling and inhibitory polysaccharide interactions with FGF-1 in
      solution.
AB  - For heparan sulfate (HS) to bind and regulate the activity of proteins, the
      polysaccharide must present an appropriate sequence and adopt a suitable
      conformation. The conformations of heparin derivatives, as models of HS, are
      altered via a change in the associated cations, and this can drastically modify
      their FGF signaling activities. Here, we report that changing the cations
      associated with an N-acetyl-enriched heparin polysaccharide, from sodium to
      copper(II), converted it from supporting signaling through the fibroblast growth
      factor receptor (FGF-1-FGFR1c) tyrosine kinase signaling system to being
      inhibitory in a cell-based BaF3 assay. Nuclear magnetic resonance and synchrotron
      radiation circular dichroism (SRCD) spectroscopy demonstrated that the
      polysaccharide conformation differed in the presence of sodium or copper(II)
      cations. Electron paramagnetic resonance confirmed the environment of the
      copper(II) ion on the N-acetyl-enriched polysaccharide was distinct from that
      previously observed with intact heparin, which supported signaling. Secondary
      structures in solution complexes of polysaccharides with FGF-1 (which either
      supported signaling through FGFR1c or were inhibitory) were determined by SRCD.
      This allowed direct comparison of the two FGF-1-polysaccharide complexes in
      solution, containing identical molecular components and differing only in their
      cation content. Subtle structural differences were revealed, including a
      reduction in the level of disordered structure in the inhibitory complex.

PMID- 19400584
TI  - Cell-penetrating HIV1 TAT peptides float on model lipid bilayers.
AB  - Cell-penetrating peptides like the cationic HIV1 TAT peptide are able to
      translocate across cell membranes and to carry molecular cargoes into the
      cellular interior. For most of these peptides, the biophysical mechanism of the
      membrane translocation is still quite unknown. We analyzed HIV1 TAT peptide
      binding and mobility within biological model membranes. To this end, we generated
      neutral and anionic giant unilamellar vesicles (GUVs) containing DPPC, DOPC, and
      cholesterol and containing DPPC, DOPC, cholesterol, and DPPS (DOPS),
      respectively. First, we characterized the mobility of fluorescently labeled
      lipids (TR-DHPE) within liquid-ordered and liquid-disordered lipid phases by
      single-molecule tracking, yielding a D(LO) of 0.6 +/- 0.05 microm(2)/s and a
      D(LD) of 2.5 +/- 0.05 microm(2)/s, respectively, as a reference. Fluorescently
      labeled TAT peptides accumulated on neutral GUVs but bound very efficiently to
      anionic GUVs. Single-molecule tracking revealed that HIV1 TAT peptides move on
      neutral and anionic GUV surfaces with a D(N,TAT) of 5.3 +/- 0.2 microm(2)/s and a
      D(A,TAT) of 3.3 +/- 0.2 mum(2)/s, respectively. TAT peptide diffusion was faster
      than fluorescent lipid diffusion, and also independent of the phase state of the
      membrane. We concluded that TAT peptides are not incorporated into but rather
      floating on lipid bilayers, but they immerged deeper into the headgroup domain of
      anionic lipids. The diffusion constants were not dependent on the TAT
      concentration ranging from 150 pM to 2 microM, indicating that the peptides were
      not aggregated on the membrane and not forming any "carpet".

PMID- 19400585
TI  - Identification, expression, and functional characterization of full-length and
      splice variants of murine organic anion transporting polypeptide 1b2.
AB  - The family of organic anion transporting polypeptides (OATPs) plays an important
      role in mediating the cellular uptake of numerous endogenous and exogenous
      compounds. Members of this family include human OATP1B1 and OATP1B3, which have
      been widely studied and shown to be involved in the hepatic uptake of hormones,
      bile acids, and many clinically used drugs. However, little is known about the
      murine orthologue, Oatp1b2. We determined expression of mouse oatp1b2 mRNA and
      protein using real-time PCR and Western blot analysis. Interestingly, mRNA
      transcripts and protein were detectable in a number of tissues including kidney
      and stomach, and, not surprisingly, the highest expression was noted in liver.
      Cloning of the full coding region of oatp1b2 revealed the presence of two novel
      splice variants. Interestingly, these splice variants were significantly
      expressed in organs such as the kidney, but much less in liver. Heterologous
      expression of the full-length Oatp1b2 cDNA revealed that taurocholic acid,
      estrone 3-sulfate, estradiol 17beta-glucuronide and pravastatin are substrates of
      this transporter. The newly identified splice variants were unable to
      significantly transport substrate compounds due to defects in cell surface
      trafficking. Our findings of murine Oatp1b2 expression and function will likely
      aid in better defining species related differences in OATP transporter function
      and the use of mouse models to predict hepatic drug disposition in humans.

PMID- 19400586
TI  - NTA directed protein nanopatterning on DNA Origami nanoconstructs.
AB  - Precisely patterning proteins and other molecules at the nanoscale is crucial to
      future biosensing and optoelectronic applications. One- and two-dimensional DNA
      nanoconstructs have proven to be useful scaffolds for nanopatterning. This paper
      demonstrates the application of nitrilotriacetic acid (NTA) forming chelate
      complexes to localize histidine (His) tagged proteins via Ni(2+) ions onto DNA
      based structures. Particularly, enhanced green fluorescent protein (EGFP) was
      directed to specific surface locations on a designed DNA Origami nanoconstruct,
      and the resulting EGFP nanopattern was visualized using atomic force microscopy
      (AFM).

PMID- 19400587
TI  - Assembly and stability of the shiga toxins investigated by electrospray
      ionization mass spectrometry.
AB  - A systematic investigation into the assembly and stability of native and modified
      subunits of the Shiga toxins (Stx) in vitro is described. Analysis of the
      assembly of native and modified B subunits of Stx1 and Stx2 in solution, carried
      out using electrospray ionization mass spectrometry (ES-MS), suggests that the
      lower thermodynamic stability of the B subunit homopentamer of Stx2, compared to
      that of Stx1, is due to the presence of a repulsive interaction involving Asp70
      of the Stx2 B subunit. In Stx1 B, the corresponding (spatially) residue is Arg.
      Using temperature-controlled ES-MS, it is shown that the Stx1 and Stx2 holotoxins
      exhibit differences in their resistance to temperature- and acid-induced
      dissociation. However, both Stx1 and Stx2 are fully assembled at pH >3.5 and 37
      degrees C. This finding has several important biological implications. First, it
      argues against the likelihood that the difference in Stx1 and Stx2 toxicity
      arises from differential dissociation of the toxins during the intracellular
      trafficking steps of the cellular intoxication process. Second, it implies that
      the activation of the A subunits of Stx1 and Stx2 by enzymatic cleavage must
      occur while the A subunit is assembled with the B subunit homopentamer. It is,
      therefore, proposed that the differential toxicities of Stx1 and Stx2 reflect the
      relative efficiencies of intracellular activation of the A subunits.

PMID- 19400588
TI  - Antipsychotic treatment alters protein expression associated with presynaptic
      function and nervous system development in rat frontal cortex.
AB  - Haloperidol and olanzapine are widely used antipsychotic drugs in the treatment
      of schizophrenia and other psychotic disorders. Despite extensive research
      efforts within the biopharmaceutical industry and academia, the exact molecular
      mechanisms of their action remain largely unknown. Since the response of patients
      to existing medications can be variable and often includes severe side effects,
      it is critical to increase our knowledge on their mechanism of action to guide
      clinical usage and new drug development. In this study, we have employed the
      label-free liquid chromatography tandem mass spectrometry (LC-MSE) to identify
      differentially expressed proteins in rat frontal cortex following subchronic
      treatment with haloperidol or olanzapine. Subcellular fractionation was performed
      to increased proteomic coverage and provided insight into the subcellular
      location involved in the mechanism of drug action. LC-MSE profiling identified
      531 and 741 annotated proteins in fractions I (cytoplasmic-) and II (membrane
      enriched-) in two drug treatments. Fifty-nine of these proteins were altered
      significantly by haloperidol treatment, 74 by olanzapine and 21 were common to
      both treatments. Pathway analysis revealed that both drugs altered similar
      classes of proteins associated with cellular assembly/organization, nervous
      system development/function (particularly presynaptic function) and neurological
      disorders, which indicate a common mechanism of action. The top affected
      canonical signaling pathways differed between the two treatments. The haloperidol
      data set showed a stronger association with Huntington's disease signaling, while
      olanzapine treatment showed stronger effects on glycolysis/gluconeogenesis. This
      could either relate to a difference in clinical efficacy or side effect profile
      of the two compounds. The results were consistent with the findings reported
      previously by targeted studies, demonstrating the validity of this approach.
      However, we have also identified many novel proteins which have not been found
      previously to be associated with these drugs. Further study of these proteins
      could provide new insights into the etiology of the disease or the mechanism of
      antipsychotic medications.

PMID- 19400589
TI  - Dramatic effect of aggregation on rates and thermodynamics of stereoisomerization
      of magnesium enolates.
AB  - Thermodynamic stereocontrol of the (hexamethyldisilazide)magnesium enolates of
      propiophenone in THF is reported. The overall stereoselectivity proves to be very
      sensitive to concentration, since dimeric species with bridging enolates show no
      stereoselectivity while monomeric enolates show a very strong thermodynamic
      preference for the Z enolate. Kinetically, interconversion among aggregates is
      remarkably slow, whereas stereoisomerization of the monomer, even in the absence
      of a proton source such as ketone or amine, is remarkably fast. Furthermore,
      stereoisomerization takes place in the absence of a proton source or excess
      ketone. These observations contrast with accepted views of these fundamentally
      important processes and have implications for understanding the identity and
      reactivity of metal enolates.

PMID- 19400590
TI  - Spatial separation of cavitating bubble populations: the nanodroplet injection
      model.
AB  - Intense Na* emission was observed from 0.1 M Na(2)SO(4) in 95% sulfuric acid
      during multibubble sonoluminescence (MBSL). As a function of acoustic intensity,
      three different morphologies are observed for the cloud of light emitting
      bubbles. Even more strikingly, there is a spatial separation between blue-white
      emitting bubbles and orange emitting bubbles, easily observed by the naked eye.
      Surprisingly, no Na* emission was observed on the top of a bubble cloud (blue
      white emission) while strong Na* emission predominates at the bottom. This
      observation provides the first experimental evidence to distinguish between the
      two types of two-site models of acoustic cavitation and MBSL: spatial separation
      of emission from nonvolatiles (e.g., Na*) ought not to be observed for the heated
      shell model but is predicted from the injected droplet model.

PMID- 19400591
TI  - A direct and nondestructive approach to determine the folding structure of the I
      motif DNA secondary structure by NMR.
AB  - I-motifs are four-stranded DNA secondary structures formed in C-rich DNA
      sequences and consist of parallel-stranded DNA duplexes zipped together in an
      antiparallel orientation by intercalated, hemiprotonated cytosine(+)-cytosine
      base pairs. I-motif structures have been indicated to form in various regions of
      the human genome as well as in nanotechnological applications. While NMR is a
      major tool for structural studies of I-motifs, the determination of the folding
      topologies of unimolecular I-motifs has been a challenging and arduous task using
      conventional NMR spectral assignment strategies, due to the inherent sequence
      redundancy of the C-rich strands in the formation of unimolecular I-motif
      structures. We report here a direct and nondestructive method that can be
      utilized to unambiguously determine the hemiprotonated C(+)-C base pairs and thus
      the folding topology of unimolecular I-motif structures formed from native C-rich
      DNA sequences. The reported approach uses affordable low-enrichment site-specific
      labeling. More significantly, the reported method can directly and unambiguously
      determine the equilibrating multiple conformations coexisting in a single DNA
      sequence, which would be a very difficult task using conventional assignment
      strategies. Additionally, this method can be applied to the direct detection of
      the base-paired thymines that are involved in the capping structures.

PMID- 19400593
TI  - Life-saving treatment for depression in elderly. Always think of
      electroconvulsive therapy (ECT).
AB  - Electroconvulsive therapy (ECT) can be both a life-enhancing and life-saving
      procedure in the elderly. Don't forget to think about recommending ECT in an
      elderly depressed patient who is suicidal or has failed multiple courses of
      antidepressants and is doing poorly.

PMID- 19400592
TI  - Binding of calcium and carbonate to polyacrylates.
AB  - Polyacrylate molecules can be used to slow the growth of calcium carbonate.
      However, little is known about the mechanism by which the molecules impede the
      growth rate. A recent computational study (Bulo et al. Macromolecules 2007, 40,
      3437) used metadynamics to investigate the binding of calcium to polyacrylate
      chains and has thrown some light on the coiling and precipitation of these
      polymers. We extend these simulations to examine the binding of calcium and
      carbonate to polyacrylate chains. We show that calcium complexed with both
      carbonate and polyacrylate is a very stable species. The free energies of calcium
      carbonate-polyacrylate complexes, with different polymer configurations, are
      calculated, and differences in the free energy of the binding of carbonate are
      shown to be due to differences in the amount of steric hindrance about the
      calcium, which prevents the approach of the carbonate ion.

PMID- 19400594
TI  - Electroconvulsive therapy for depressive episodes: A brief review.
AB  - A representative case is presented to provide a forum for a brief review of
      electroconvulsive therapy (ECT), a treatment that remains safe and effective in
      treating several psychiatric and neuropsychiatric conditions. The history,
      indications, efficacy, adverse events, treatment course, and aftercare are
      discussed in order to provide the reader a general introduction to this useful
      procedure.

PMID- 19400595
TI  - The eyelids: some common disorders seen in everyday practice.
AB  - The eyelids, essential to protecting and cleansing the eye, are a common site for
      a range of disorders affecting older adults. Some of these are benign and some
      serious, with the most clinically important being suspicious lid lesions that may
      harbor malignancy and neurologic disorders, as well as structural malpositions
      that cause poor lid function and may lead to globe damage and visual impairment.
      The ability to recognize eyelid problems is important, as they often present
      first to the primary care physician. Some eyelid disorders can be successfully
      treated quickly and easily in the office setting, whereas others may be chronic
      and more difficult to manage, requiring referral to an ophthalmologist or
      oculoplastic specialist.

PMID- 19400596
TI  - Update on neuropsychiatric symptoms of dementia: evaluation and management.
AB  - The neuropsychiatric symptoms of dementia can lead to a decreased quality of
      life, rapid cognitive decline, early patient institutionalization, tremendous
      caregiver burden, and increased cost of care. A thorough assessment to evaluate
      and treat any underlying causes of symptoms is essential. With the lack of an
      approved drug to treat the neuropsychiatric symptoms of dementia,
      nonpharmacologic interventions take on added importance. Behavioral management,
      cognitive stimulation therapy, and caregiver and health care staff education have
      shown the most promise to reduce symptom burden over the long term. The
      antipsychotic drugs have been the traditional choice of medications to treat the
      neuropsychiatric symptoms of dementia, but safety problems emerged with their
      use, leading to the issuance of label changes ("black box" warnings) by the Food
      and Drug Administration. Aside from antipsychotic drugs, multiple classes of
      medications have been tried to treat such symptoms but long-term data showing
      efficacy and safety are often lacking.

PMID- 19400597
TI  - Acute effects of the antibiotic oxytetracycline on the bacterial community of the
      grass shrimp, Palaemonetes pugio.
AB  - The toxicity of oxytetracycline (OTC) was evaluated in adult grass shrimp,
      Palaemonetes pugio. Initially, static acute (96 h) toxicity tests were conducted
      with shrimp exposed from 0 to 1,000 mg/L OTC. A calculated lethal concentration
      50% value of 683.30 mg/L OTC (95% confidence interval 610.85-764.40 mg/L) was
      determined from these tests, along with a lowest-observable-effect concentration
      of 750 mg/L and no-observable-effect concentration of 500 mg/L. Moreover, chronic
      sublethal effects of OTC exposure on grass shrimp intestinal bacterial population
      were assessed using doses from 0 to 32 mg/L OTC. The total viable counts in
      digestive tract content had levels between 5.2 and 1x10(4) colony-forming units
      per gram of tissue at times 0 and 96 h, respectively. Aeromonas hydrophila were
      the most resistant isolates (27.78%) to OTC exposure. Vibrio alginolyticus showed
      significant positive growth following exposure to OTC, whereas other bacterial
      species abundance declined over time. A total of 268 bacterial isolates were
      screened using antibiotic resistance analysis from a library containing 459
      isolates. Among the tested isolates from the OTC treatments, 15.4% were resistant
      to OTC and 84.6% were OTC sensitive. Oxytetracycline was generally not
      consistently quantifiable with liquid chromatography-mass spectroscopy technique
      in shrimp homogenates. The only peak detected was at the 32 mg/L dose of OTC at
      96 h. Nevertheless, OTC had a significant biological effect on the bacterial
      population. Antibiotic resistance to five other antibiotics (penicillin G,
      sulfathiazole, trimethoprim, trimethoprim and sulfamethoxazole, and tetracycline)
      was strongly associated with OTC exposures. The present study indicates that OTC
      toxicity effects in P. pugio and changes in the shrimp microbial community would
      only be expected under special circumstances.

PMID- 19400598
TI  - The prevalence of hepatitis B surface antigen and anti-hepatitis B core antibody
      in Iran: a population-based study.
AB  - BACKGROUND: Hepatitis B virus infection is a very common cause of chronic liver
      disease worldwide. It is estimated that 3% of Iranians are chronically infected
      with hepatitis B virus. Current population-based studies on both rural and urban
      prevalence of hepatitis B virus infection in Iran are sparse with results that do
      not always agree. We performed this study to find the prevalence of hepatitis B
      surface antigen, anti-hepatitis B core antibody, and associated factors in the
      general population of three provinces of Iran. METHODS: We randomly selected
      6,583 subjects from three provinces in Iran, namely Tehran, Golestan, and
      Hormozgan. The subjects were aged between 18 and 65 years. Serum samples were
      tested for hepatitis B surface antigen and anti-hepatitis B core antibody.
      Various risk factors were recorded and multivariate analysis was performed.
      RESULTS: The prevalence of hepatitis B surface antigen and anti-hepatitis B core
      antibody in Iran was 2.6% and 16.4%, respectively. Predictors of hepatitis B
      surface antigen or anti-hepatitis B core antibody in multivariate analysis
      included older age, not having high-school diploma, living in a rural area, and
      liver disease in a family member. We did not find any significant differences
      between males and females. CONCLUSION: In spite of nationwide vaccination of
      newborns against hepatitis B virus since 1992, hepatitis B virus infection
      remains a very common cause of chronic liver disease in Iran which should be
      dealt with for at least the next 30-50 years.

PMID- 19400599
TI  - Water pipe smoking and health-related quality of life: a population-based study.
AB  - BACKGROUND: Water pipe smoking is increasing in Eastern Mediterranean Region. The
      objective of this study was to investigate any relationship between water pipe
      smoking and health-related quality of life in the general population of Bandar
      Abbas, Iran. METHODS: Using a multistage sampling method, a random sample of 1675
      individuals aged 15 years and over was studied from June through July 2007. All
      eligible participants were interviewed using the Short Form Health Survey (SF-36)
      questionnaire and a short questionnaire containing items regarding socio
      demographic characteristics and water pipe smoking status. To compare SF-36
      scores between water pipe smokers and nonsmokers, t-test was performed. In
      addition, multiple logistic regression analysis was used to determine the
      influence of water pipe smoking on SF-36 scores after adjusting for other
      independent variables. RESULTS: In all, 1675 individuals were studied. The mean
      age of the respondents was 42.1 (SD=16.5) years. One hundred and seventy-two
      participants (10.4%) were water pipe smokers. There were statistically
      significant differences between water pipe smokers and nonsmokers on all scales
      except for role emotional (P<0.001). Logistic regression analysis showed that
      using water pipe was a risk factor for decreasing Physical Component Summary and
      Mental Component Summary scores [OR (95% CI): 2.15 (1.56-2.96), P<0.01; and OR
      (95% CI): 1.88 (1.36-2.60), P<0.01, respectively]. CONCLUSION: The study findings
      indicated that people who smoked water pipe carried a higher risk for poorer
      health-related quality of life.

PMID- 19400600
TI  - Genotype analysis of hepatitis delta virus from hepatitis B surface antigen
      positive patients using PCR-RFLP in Tehran, Iran.
AB  - BACKGROUND: Hepatitis delta virus is a unique human pathogen responsible for some
      20 million infections globally. This virus is dependent on hepatitis B virus for
      transmission and propagation. Currently, at least three genotypes of hepatitis
      delta virus with different geographic distribution and clinical manifestations
      are described. METHODS: In this study, hepatitis delta virus RNA of 35 patients'
      sera were analyzed by RT- semi-nested polymerase chain reaction. Based on genomic
      differences of hepatitis delta antigen coding region of hepatitis delta virus RNA
      among hepatitis delta virus RNA-positive sera, the polymerase chain reaction
      products were digested with restriction enzymes and studied by restriction
      fragment length polymorphism. RESULTS: Out of 35 samples, 13 (38.46%) were
      positive for hepatitis delta virus RNA by RT- semi-nested polymerase chain
      reaction. All polymorphisms were shown to be genotype I. Out of 13 hepatitis
      delta virus RNA-positive (13/35), eight were HBeAg negative. CONCLUSION: Our data
      indicated that hepatitis delta virus isolates in Tehran are exclusively genotype
      I.

PMID- 19400601
TI  - Post-traumatic stress disorder in bam-survived students who immigrated to Kerman,
      four months after the earthquake.
AB  - BACKGROUND: The 6.3 Richter earthquake in Bam killed 26,000 and injured 30,000
      people, and destroyed 85% of houses according to the literature. Children are
      affected more than others by disasters. In this study, we assessed the rate of
      post-traumatic stress disorder and psychological problems in survived Bam
      students in Kerman four months after the earthquake and their relations with
      demographic factors, family loss, house destruction, and body injury. METHODS: A
      group of 433 students attended this cross sectional study. Watson post traumatic
      stress disorder questionnaire and Symptom Checklist-90 were applied for students
      older than 15 years of age and Yule post-traumatic stress disorder and Rutter
      (parents' version) questionnaires were used for students younger than 15.
      Multiple regression analysis was used to assess the effects of variables on
      psychopathologies. RESULTS: Post-traumatic stress disorder was detected in 36.3%
      of the students older than 15 years of age and 51.6% of the students younger than
      15. Behavioral problems were present in 31.3% of the children and the mean score
      of Global Symptom Index was 1.13+/-0.59. Body injury and living with family were
      correlated with post-traumatic stress disorder and Symptom Checklist-90 items in
      students older than 15. Female sex was correlated with post-traumatic stress
      disorder and behavioral problems in students younger than 15. CONCLUSION: The
      prevalence of post-disaster post-traumatic stress disorder was high in children.
      Younger age, female gender, living apart from family, geographic living
      conditions, being in the center of stress or not after the earthquake, body
      injury, and loss of family members form the basis for developing post-disaster
      psychopathology. Due to incomplete presence of post-traumatic stress disorder
      criteria or high rate of overlooking post-traumatic stress disorder in children,
      the disorder may be misdiagnosed or remain undiagnosed in them, which warrants
      more consideration.

PMID- 19400602
TI  - Renal artery stenosis in hypertensive patients with or without type 2 diabetes: a
      comparative magnetic resonance angiography study.
AB  - BACKGROUND: Increased prevalence of various vascular diseases is common in type 2
      diabetes mellitus. However, the increased prevalence of renal artery atheroma
      resulting in renal artery stenosis in patients with diabetes mellitus has not
      been fully assessed. We used magnetic resonance angiography to assess the
      prevalence of renal artery stenosis in a group of patients with hypertension and
      type 2 diabetes mellitus and compared them with a group of hypertensive patients
      without diabetes. METHODS: One hundred and seventy-three individuals were
      recruited consecutively in this study. They were divided into two groups: 50
      patients with known type 2 diabetes and coexistent hypertension in group A and
      123 hypertensive patients without diabetes in group B. All the patients underwent
      magnetic resonance angiography of the renal arteries to assess the presence of
      renal artery stenosis. RESULTS: The prevalence of renal artery stenosis in groups
      A and B was 44% and 35.8%, respectively (P=0.402). However, there was a
      significant association between the age and renal artery stenosis (P=0.023).
      CONCLUSION: Diabetes mellitus was not associated with the increased prevalence of
      renal artery stenosis in our study.

PMID- 19400603
TI  - Reference values for lung volumes in an Iranian population: introducing a new
      equation model.
AB  - BACKGROUND: Measurement of lung volumes, especially residual volume and total
      lung capacity are essential for assessment of restrictive lung disorders.
      Information regarding normative prediction values for lung volumes as measured by
      body plethysmography is scarce, and plethysmographic parameters are believed to
      be poorly reproducible. In this study, we report a comprehensive set of
      predictive equations for static lung volumes from a general population sample of
      urban Iranians as measured by body plethysmography. METHODS: Standardized
      measurements were carried out on 1487 healthy nonsmoking volunteers (845 men and
      642 women), aged six to 85 years, living in Isfahan, Iran. Nonlinear multiple
      regression analysis was used to calculate prediction equations based on subjects'
      ages and heights for the subdivisions of lung volumes [total lung capacity,
      functional residual capacity, residual volume, and residual volume/total lung
      capacity (%)], separately for the two genders. The derived equations were used to
      calculate prediction values for the subjects. The two sets of predicted and
      measured values were compared by paired sample t-test. RESULTS: Prediction
      equations based on a new nonlinear model, (alpha(1) x age + alpha(2) x age(n) +
      beta x height + c) which best fitted our data are presented. The measured and
      predicted values closely resemble and there is no significant difference between
      the two sets. Since increments in total lung capacity, functional residual
      capacity, and residual volume disclose air trapping within the lungs, their upper
      limits of normal are as important as the lower limits. So, we have presented both
      for the equations. CONCLUSION: Despite the usual beliefs we found rather
      reproducible prediction equations with high coefficient of determination (r2) and
      low standard error of estimate (SEE) in Iranian population.

PMID- 19400604
TI  - The prevalence of thyroid dysfunction in an iodine-sufficient area in Iran.
AB  - BACKGROUND: The prevalence of hypothyroidism in Iran is unknown. The aims of the
      present study were to estimate the prevalence of overt and subclinical
      hypothyroidism among the adult population of Isfahan, a large metropolitan city
      in Iran, 15 years after universal salt iodization. METHODS: A cross-sectional
      survey was conducted from January 2006 through April 2006. The selection was
      conducted by stratified probability cluster sampling through household family
      members in Isfahan, Iran. Thyroid stimulating hormone (TSH) of 2523 men and women
      aged >20 years (mean: 39.0) was measured. Additional thyroid tests were done and
      serum levels of antithyroid antibodies were evaluated in individuals with
      elevated TSH. Elevated TSH with normal free T4 index (FT4I) at the second
      measurement was considered as subclinical and high TSH with low FT4I as overt
      hypothyroidism. RESULTS: The overall prevalence of hypothyroidism was 4.8% [95%
      confidence interval (CI) 3.7, 6.1] in men and 12.8% (95% CI 10.9, 14.6) in women;
      and 37.6% of hypothyroid men and women had positive antithyroperoxidase
      antibodies and/or antithyroglobulin antibody, while 19.3% of men and women were
      euthyroid. The mean (SE) of urinary iodine was 20.3 (0.55) microg/dL and 20.1
      (1.37) microg/dL for euthyroid and hypothyroid individuals, respectively
      (P=0.65). Older age, female sex, and goiter were strongly associated with both
      overt and subclinical hypothyroidism. CONCLUSION: Hypothyroidism appears to be
      common in Isfahan, Iran. The high prevalence of hypothyroidism in Isfahan may be
      due to autoimmunity with no correlation to iodine intake.

PMID- 19400605
TI  - A survey of the current status of web-based databases indexing Iranian journals.
AB  - BACKGROUND: The scientific output of Iran is increasing rapidly during the recent
      years. Unfortunately, most papers are published in journals which are not indexed
      by popular indexing systems and many of them are in Persian without English
      translation. This makes the results of Iranian scientific research unavailable to
      other researchers, including Iranians. The aim of this study was to evaluate the
      quality of current web-based databases indexing scientific articles published in
      Iran. METHODS: We identified web-based databases which indexed scientific
      journals published in Iran using popular search engines. The sites were then
      subjected to a series of tests to evaluate their coverage, search capabilities,
      stability, accuracy of information, consistency, accessibility, ease of use, and
      other features. Results were compared with each other to identify strengths and
      shortcomings of each site. RESULTS: Five web sites were indentified. None had a
      complete coverage on scientific Iranian journals. The search capabilities were
      less than optimal in most sites. English translations of research titles, author
      names, keywords, and abstracts of Persian-language articles did not follow
      standards. Some sites did not cover abstracts. Numerous typing errors make
      searches ineffective and citation indexing unreliable. CONCLUSION: None of the
      currently available indexing sites are capable of presenting Iranian research to
      the international scientific community. The government should intervene by
      enforcing policies designed to facilitate indexing through a systematic approach.
      The policies should address Iranian journals, authors, and indexing sites.
      Iranian journals should be required to provide their indexing data, including
      references, electronically; authors should provide correct indexing information
      to journals; and indexing sites should improve their software to meet standards
      set by the government.

PMID- 19400606
TI  - Different aspects of psoriasis: analysis of 150 Iranian patients.
AB  - BACKGROUND: Psoriatic arthritis is defined as an inflammatory arthritis
      associated with psoriasis and is classified as a seronegative HLA-B27-associated
      spondyloarthropathy. We aimed to study the clinical and paraclinical
      presentations of psoriatic arthritis in 150 Iranian patients. METHODS:
      Demographic, clinical, and paraclinical data obtained from 150 patients enrolled
      in a retro- and introspective study were analyzed. RESULTS: The female:male ratio
      was 1.11:1. The mean age at the onset of arthritis was 33.3 years. Arthritis
      occurred after psoriasis in 73%, preceded it in 17%, and simultaneously in 10% of
      the patients. The patterns of joint involvement were asymmetric oligoarthritis
      (46%), polyarthritis (5%), axial involvement (16%), distal interphalangeal joint
      involvement (23%), and mutilating arthritis (2.2%). There was no correlation
      between distal interphalangeal joint involvement and nail disease (P=0.33).
      Polyarthritis was more common in women (P=0.03) and axial involvement was more in
      men (P=0.02). Patients with spondylitis were younger at the disease onset
      (P<0.02). Dactylitis was seen in 12% of the patients. Enthesopathy (20.7%) was
      more common in patients with axial involvement (P=0.008) and joint deformity
      (15%) was more common in patients with polyarthritis or distal interphalangeal
      joint involvement (P<0.0002). Four patients had ocular inflammation. Anemia was
      detected in 24%, high erythrocyte sedimentation rate in 79%, and abnormal urinary
      indices in 9% of the patients. There was a significant correlation between HLA
      B27 (16%) and axial involvement (P=0.01) as well as joint erosions (16%) and
      distal interphalangeal joint involvement (P<0.0001). Thirty-four patients (26.8%)
      showed radiographic findings of sacroiliitis, while only 14 of them had axial
      involvement. CONCLUSION: Oligoarthritis was the most common type of joint
      involvement in these Iranian patients. We found no correlation between distal
      interphalangeal joint involvement and nail changes, although it was seen with
      more erosive changes and joint deformity. In comparison with other studies, extra
      articular manifestations were not common in our patients.

PMID- 19400607
TI  - Adverse health outcomes of road traffic injuries in Iran after rapid
      motorization.
AB  - Recent studies have made it clear that Iran has too many road traffic injuries
      (RTI). This paper explains the reasons for high traffic injury rates and points
      to solutions. It also provides detailed data on the burden of traffic injury in
      Iran in 2005. Traffic injury rates have rapidly risen out of control because for
      a variety of possible reasons such as increasing number of non-standard cars and
      motorcycles, low gas price, decreasing ratio of travels via public transportation
      than with private vehicles, and problems with safety design. Besides a high need
      for a system safety approach, Iran needs to deal with the problem of producing a
      high number of cars and motorcycles. Providing safe mobility for the people of
      Iran needs to be a top priority of the government.

PMID- 19400608
TI  - Hydroxyurea therapy in 49 patients with major beta-thalassemia.
AB  - Major thalassemia is one of the most common hemoglobinopathies in many Asian
      countries including Iran. Pharmacologic agents such as hydroxyurea have been
      known to enhance the production of fetal hemoglobin, and also an increase in
      total hemoglobin level has been repeatedly reported during hydroxyurea treatment
      in patients with sickle cell disease and in several patients with intermediate
      beta-thalassemia. We evaluated the long-term efficacy and safety of hydroxyurea
      in major beta-thalassemic patients. Forty-nine beta-thalassemic patients enrolled
      in the study. The mean follow-up time was 60 months. The mean dose of hydroxyurea
      was 10 mg/kg per day (8-15 mg/kg). Before starting hydroxyurea, all patients
      underwent routine biochemical laboratory tests. Patients with low platelet count
      (<100,000/mm3), neutropenia (polymorphonuclear neutrophil<1,200/mm3), pregnancy,
      and on interferon treatment were excluded.Twenty-eight out of 49 enrolled
      patients were females with the mean age of 18.38 years (10-40 years). The mean
      packed red cell transfusions during one year before starting of hydroxyurea was
      22.75 units which decreased to 6.02 units after treatment (P<0.01). The mean
      ferritin level during the first period was 2751.44 ng/mL, but decreased to
      1594.20 ng/mL after one year of hydroxyurea therapy (P<0.001).We observed a
      substantial and persistent increase in hemoglobin level and a significant
      decrease in blood transfusion. Hydroxyurea treatment was well-tolerated and it
      did not cause any hematopoietic suppression except in one patient who developed
      transient thrombocytopenia which resolved after short period of hydroxyurea
      cessation. We did not encounter any malignancies including leukemia in the five
      year follow-up.

PMID- 19400609
TI  - Attitudes of healthcare providers towards patients with HIV/AIDS in Bandar Abbas.
AB  - We aimed to investigate the attitudes of healthcare providers towards patients
      with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS)
      in Bandar Abbas, south of Iran. In this cross-sectional study, a random sample of
      250 healthcare providers completed a 20-item questionnaire from January first
      through February 30th, 2007. There were five domains of attitudes towards
      patients with HIV. The items measured as a five-point Likert scale ranging from
      strongly disagree to strongly agree. The mean age of the healthcare providers was
      31.3 (SD=7.3) years. Of them 24.4% were males, 42.4% had received Bachelor of
      Science degree, 19.2% were physicians, 63.2% were nurses, and 17.6% were
      laboratory technicians. The respondents had fairly positive attitudes towards
      patients with HIV. Men, older age, more educated participants, and laboratory
      technicians had more favorable attitude towards HIV (P<0.05).

PMID- 19400610
TI  - Read the articles; don't count them.

PMID- 19400611
TI  - Desmoplastic ameloblastoma (a hybrid variant): report of a case and review of the
      literature.
AB  - Desmoplastic ameloblastoma is an unusual type of ameloblastoma with special
      histologic and radiographic features and anatomic distribution which differs from
      those in the classic type of ameloblastoma. The purpose of this article is to
      assist the dental community in better understanding of this variation of
      odontogenic tumor. We present a patient with desmoplastic and conventional
      variant of ameloblastoma (hybrid lesion) localized in the anterior portion of the
      mandible. The tumor was expansile and painless. The radiographic finding showed
      an ill-defined mixed (radiopaque/radiolucent) lesion between roots of the lower
      left canine and the lateral incisor. Marginal resection was performed. Follow-up
      examination one year later revealed no recurrence of the tumor. Desmoplastic
      variant of ameloblastoma tends to infiltrate between bone trabeculae. Curettage
      leaves islands of the tumor within bone, which later manifest as recurrences.
      Therefore, for big lesions en bloc excision is the most widely used treatment to
      avoid recurrence.

PMID- 19400612
TI  - Peripheral calcifying odontogenic cyst.
AB  - Calcifying odontogenic cyst is a rare lesion representing about 1% of jaw cysts.
      It may occur in a central (intraosseous) or peripheral (extraosseous) location. A
      case of peripheral calcifying odontogenic cyst located on the gingiva, appearing
      as a painless, circumscribed, sessile, and pink to red nodule has been
      reported.Peripheral, in contrast to central, calcifying odontogenic cyst tends to
      affect older patients. Peripheral calcifying odontogenic cyst is a less
      aggressive lesion than the central counterpart, and a simple excision biopsy is
      curative. The histologic findings of an epithelium rich in ghost cells has helped
      in making the diagnosis.

PMID- 19400613
TI  - Acute myocardial infarction in a patient with Behcet's disease.
AB  - A 37-year-old man, a known case of Behcet's disease with its vascular
      complications such as abdominal and thoracic artery aneurysms, was admitted with
      the diagnosis of acute anterior myocardial infarction and received thrombolytic
      therapy. Coronary angiography and percutaneous coronary intervention via
      transradial approach were performed for the patient on the eighth day of
      admission. The patient did not suffer from any symptoms, myocardial infarction,
      or readmission in the nine-month follow-up. About 25 cases of myocardial
      infarction associated with Behcet's disease have been reported previously.
      Although coronary involvement is rare in Behcet's disease, it is especially
      important because it affects young individuals and often presents as acute
      coronary syndromes.

PMID- 19400614
TI  - Concomitant Hodgkin's lymphoma and atopic dermatitis in a child with Celiac
      disease.
AB  - Celiac disease is an autoimmune disease associated with increased risk of several
      diseases including a variety of malignancies. This is the first report of the
      concomitance of atopic dermatitis and Hodgkin's lymphoma in a child with celiac
      disease. Here, we report an 11-year-old boy with chronic diarrhea, glossitis,
      chronic dermatitis, and megaloblastic anemia who later developed Hodgkin's
      lymphoma.

PMID- 19400615
TI  - Photoclinic: Anthrax.

PMID- 19400616
TI  - In commemoration of Haj Mohammad Nemazee (1895-1972): the founder of Nemazee
      Hospital in Shiraz.
AB  - Nemazee Hospital in Shiraz, Fars Province, in southern Iran is a well-equipped
      modern hospital, which was founded in 1955. It is one of the greatest memorials
      of a Shirazi beneficent merchant, the late Haj Mohammad Nemazee (1895-1972), who
      dedicated much of his wealth to charitable affairs in his birthplace. This paper
      briefly explores the history of the establishment of Nemazee Hospital in Shiraz.

PMID- 19400617
TI  - Tea drinking habits and oesophagial cancer in a high-risk area in northern Iran:
      population based case-control study.
AB  - In a recently published paper in the "British Medical Journal", a joint
      collaboration of well-known international scientists represented by Islami et al.
      has tackled this issue.1 In a well-designed, laborious case-control study in
      Golestan, Iran, they looked at 300 cases of esophageal SCC and 571 age and sex
      matched neighborhood controls, assessed the temperature of the commonly used
      drink "tea" among them and compared it between the two groups. After adjusting
      for several confounders including ethnicity, daily vegetable intake, alcohol
      consumption, tobacco or opium use, duration of residence in rural areas,
      education level and car ownership (the latter two as indices of socio-economic
      status), they found that consuming hot tea is associated with significantly
      increased chance of developing esophageal SCC. The adjusted odds ratio(OR) for
      developing esophageal SCC in those who reported drinking "very hot tea" was 8.16
      (95% CI: 3.93 to 16.91) as compared to those taking warm or lukewarm tea
      (P<0.001) and for those drinking "hot" tea the adjusted OR was 2.07 (95% CI: 1.28
      to 3.35). According to Islami et al., 21.1% and 36.2% of the cases drank their
      tea "very hot" or "hot", respectively. Self-claim of "hot", "very hot", and "warm
      or "lukewarm" tea drinking correlated with the claimed time from pouring tea to
      its drinking by the individual (weighted kappa statistics: 0.69). They did not
      find any correlation between amount of tea consumed and development of esophageal
      SCC. They have also reported limited data of tea temperature measurement in
      addition to the self claims of tea drinking habits (as mentioned for the case
      control study) from a large on-going cohort study in the same region. The authors
      conclude that it is probably the "hotness" rather than the "tea" which is
      responsible for this increased chance of SCC of esophagus. In an accompanying
      editorial, Whiteman suggests that people drink their tea at least 5 minutes after
      pouring it in their cups.

PMID- 19400618
TI  - Concepts and concept formation.

PMID- 19400619
TI  - Judgment and decision: theory and application.

PMID- 19400620
TI  - Life-span development.

PMID- 19400621
TI  - Human learning and memory.

PMID- 19400622
TI  - Attitudes and attitude change.

PMID- 19400623
TI  - Current issues in attribution theory and research.

PMID- 19400624
TI  - Psychological issues in personnel decisions.

PMID- 19400625
TI  - Personnel training.

PMID- 19400626
TI  - Child psychology.

PMID- 19400627
TI  - Organizational behavior: a review and reformulation of the field's outcome
      variables.

PMID- 19400628
TI  - Personality assessment.

PMID- 19400629
TI  - Cell growth characteristics, differentiation frequency, and immunophenotype of
      adult ear mesenchymal stem cells.
AB  - Ear mesenchymal stem cells (EMSCs) represent a readily accessible population of
      stem-like cells that are adherent, clonogenic, and have the ability to self
      renew. Previously, we have demonstrated that they can be induced to differentiate
      into adipocyte, osteocyte, chondrocyte, and myocyte lineages. The purpose of the
      current study was to characterize the growth kinetics of the cells and to
      determine their ability to form colonies of fibroblasts, adipocytes, osteocytes,
      and chondrocytes. In addition, the immunophenotypes of freshly isolated and
      culture-expanded cells were evaluated. From 1 g of tissue, we were able to
      isolate an average of 7.8 x 10(6) cells exhibiting a cell cycle length of
      approximately 2-3 days. Colony-forming unit (CFU) assays indicated high
      proliferation potential, and confirmed previously observed multipotentiality of
      the cells. Fluorescence-activated cell sorting (FACS) showed that EMSCs were
      negative for hematopoietic markers (CD4, CD45), proving that they did not derive
      from circulating hematopoietic cells. The FACS analyses also showed high
      expression of stem cell antigen-1 (Sca-1) with only a minor population of cells
      expressing CD117, thus identifying Sca-1 as the more robust stem cell biomarker.
      Additionally, flow cytometry data revealed that the expression patterns of
      hematopoietic, stromal, and stem cell markers were maintained in the passaged
      EMSCs, consistent with the persistence of an undifferentiated state. This study
      indicates that EMSCs provide an alternative model for in vitro analyses of adult
      mesenchymal stem cells (MSCs). Further studies will be necessary to determine
      their utility for tissue engineering and regenerative medical applications.

PMID- 19400631
TI  - Fungal effector proteins.
AB  - It is accepted that most fungal avirulence genes encode virulence factors that
      are called effectors. Most fungal effectors are secreted, cysteine-rich proteins,
      and a role in virulence has been shown for a few of them, including Avr2 and Avr4
      of Cladosporium fulvum, which inhibit plant cysteine proteases and protect chitin
      in fungal cell walls against plant chitinases, respectively. In resistant plants,
      effectors are directly or indirectly recognized by cognate resistance proteins
      that reside either inside the plant cell or on plasma membranes. Several secreted
      effectors function inside the host cell, but the uptake mechanism is not yet
      known. Variation observed among fungal effectors shows two types of selection
      that appear to relate to whether they interact directly or indirectly with their
      cognate resistance proteins. Direct interactions seem to favor point mutations in
      effector genes, leading to amino acid substitutions, whereas indirect
      interactions seem to favor jettison of effector genes.

PMID- 19400634
TI  - Viruses of plant pathogenic fungi.
AB  - Mycoviruses are widespread in all major groups of plant pathogenic fungi. They
      are transmitted intracellularly during cell division, sporogenesis, and cell
      fusion, but apparently lack an extracellular route for infection. Their natural
      host ranges are limited to individuals within the same or closely related
      vegetative compatibility groups. Recent advances, however, allowed the
      establishment of experimental host ranges for a few mycoviruses. Although the
      majority of known mycoviruses have dsRNA genomes that are packaged in isometric
      particles, an increasing number of usually unencapsidated mycoviruses with
      positive-strand RNA genomes have been reported. We discuss selected mycoviruses
      that cause debilitating diseases and/or reduce the virulence of their
      phytopathogenic fungal hosts. Such fungal-virus systems are valuable for the
      development of novel biocontol strategies and for gaining an insight into the
      molecular basis of fungal virulence. The availability of viral and host genome
      sequences and of transformation and transfection protocols for some plant
      pathogenic fungi will contribute to progress in fungal virology.

PMID- 19400635
TI  - The biology of viroid-host interactions.
AB  - Viroids are single-stranded, circular, and noncoding RNAs that infect plants.
      They replicate in the nucleus or chloroplast and then traffic cell-to-cell
      through plasmodesmata and long distance through the phloem to establish systemic
      infection. They also cause diseases in certain hosts. All functions are mediated
      directly by the viroid RNA genome or genome-derived RNAs. I summarize recent
      advances in the understanding of viroid structures and cellular factors enabling
      these functions, emphasizing conceptual developments, major knowledge gaps, and
      future directions. Newly emerging experimental systems and research tools are
      discussed that are expected to enable significant progress in a number of key
      areas. I highlight examples of groundbreaking contributions of viroid research to
      the development of new biological principles and offer perspectives on using
      viroid models to continue advancing some frontiers of life science.

PMID- 19400636
TI  - Hyaloperonospora Arabidopsidis as a pathogen model.
AB  - Hyaloperonospora arabidopsidis, a downy mildew pathogen of the model plant
      Arabidopsis, has been very useful in the understanding of the relationship
      between oomycetes and their host plants. This naturally coevolving pathosystem
      contains an amazing level of genetic diversity in host resistance and pathogen
      avirulence proteins. Oomycete effectors identified to date contain a targeting
      motif, RXLR, enabling effector entry into the host cell. The availability of the
      H. arabidopsidis genome sequence has enabled bioinformatic analyses to identify
      at least 130 RXLR effectors, potentially used to quell the host's defense
      mechanism and manipulate other host cellular processes. Currently, these
      effectors are being used to reveal their targets in the host cell. Eventually
      this will result in an understanding of the mechanisms used by a pathogen to
      sustain a biotrophic relationship with a plant.

PMID- 19400637
TI  - Pathogen refuge: a key to understanding biological control.
AB  - Pathogen refuge is the idea that some potentially infectious pathogen propagules
      are not susceptible to the influence of an antagonistic microbial agent. The
      existence of a refuge can be attributable to one or more factors, including
      temporal, spatial, structural, and probabilistic, or to the pathogen's evolved
      ability to acquire antagonist-free space prior to ingress into a plant host.
      Within a specific pathosystem, refuge size can be estimated in experiments by
      measuring the proportion of pathogen propagules that remain infective as a
      function of the amount of antagonist introduced to the system. Refuge size is
      influenced by qualities of specific antagonists and by environment but less so by
      the quantity of antagonist. Consequently, most efforts to improve and optimize
      biological control are in essence efforts to reduce refuge size. Antagonist
      mixtures, optimal timing of antagonist introductions, integrated biological and
      chemical control, environmental optimization, and the utilization of disarmed
      pathogens as antagonists are strategies with potential to minimize a pathogen
      refuge.

PMID- 19400638
TI  - Xanthomonas AvrBs3 family-type III effectors: discovery and function.
AB  - Xanthomonads are bacterial plant pathogens that cause diseases on many plant
      species, including important crops. Key to pathogenicity of most Xanthomonas
      pathovars is a Hrp-type III secretion (T3S) system that translocates effector
      proteins into plant cells. Within the eukaryotic cell, the effectors are thought
      to perform a variety of tasks to support bacterial virulence, proliferation, and
      dissemination. We are only beginning to understand the host targets of different
      effectors. The largest effector family found in Xanthomonas spp. is the
      AvrBs3/PthA or TAL (transcription activator-like) family. TAL effectors act as
      transcriptional activators in the plant cell nucleus. Specificity of TAL
      effectors is determined by a novel modular DNA-binding domain. Here, we describe
      the discovery of TAL effectors and their structure, activity, and host targets.

PMID- 19400639
TI  - Hidden fungi, emergent properties: endophytes and microbiomes.
AB  - Endophytes are microorganisms that live within plant tissues without causing
      symptoms of disease. They are important components of plant microbiomes.
      Endophytes interact with, and overlap in function with, other core microbial
      groups that colonize plant tissues, e.g., mycorrhizal fungi, pathogens,
      epiphytes, and saprotrophs. Some fungal endophytes affect plant growth and plant
      responses to pathogens, herbivores, and environmental change; others produce
      useful or interesting secondary metabolites. Here, we focus on new techniques and
      approaches that can provide an integrative understanding of the role of fungal
      endophytes in the plant microbiome. Clavicipitaceous endophytes of grasses are
      not considered because they have unique properties distinct from other
      endophytes. Hidden from view and often overlooked, endophytes are emerging as
      their diversity, importance for plant growth and survival, and interactions with
      other organisms are revealed.

PMID- 19400640
TI  - The genomes of root-knot nematodes.
AB  - Plant-parasitic nematodes are the most destructive group of plant pathogens
      worldwide and are extremely challenging to control. The recent completion of two
      root-knot nematode genomes opens the way for a comparative genomics approach to
      elucidate the success of these parasites. Sequencing revealed that Meloidogyne
      hapla, a diploid that reproduces by facultative, meiotic parthenogenesis, encodes
      approximately 14,200 genes in a compact, 54 Mpb genome. Indeed, this is the
      smallest metazoan genome completed to date. By contrast, the 86 Mbp Meloidogyne
      incognita genome encodes approximately 19,200 genes. This species reproduces by
      obligate mitotic parthenogenesis and exhibits a complex pattern of aneuploidy.
      The genome includes triplicated regions and contains allelic pairs with
      exceptionally high degrees of sequence divergence, presumably reflecting
      adaptations to the strictly asexual reproductive mode. Both root-knot nematode
      genomes have compacted gene families compared with the free-living nematode
      Caenorhabditis elegans, and both encode large suites of enzymes that uniquely
      target the host plant. Acquisition of these genes, apparently via horizontal gene
      transfer, and their subsequent expansion and diversification point to the
      evolutionary history of these parasites. It also suggests new routes to their
      control.

PMID- 19400641
TI  - Ustilago maydis as a Pathogen.
AB  - The Ustilago maydis-maize pathosystem has emerged as the current model for plant
      pathogenic basidiomycetes and as one of the few models for a true biotrophic
      interaction that persists throughout fungal development inside the host plant.
      This is based on the highly advanced genetic system for both the pathogen and its
      host, the ability to propagate U. maydis in axenic culture, and its unique
      capacity to induce prominent disease symptoms (tumors) on all aerial parts of
      maize within less than a week. The corn smut pathogen, though economically not
      threatening, will continue to serve as a model for related obligate biotrophic
      fungi such as the rusts, but also for closely related smut species that induce
      symptoms only in the flower organs of their hosts. In this review we describe the
      most prominent features of the U. maydis-maize pathosystem as well as genes and
      pathways most relevant to disease. We highlight recent developments that place
      this system at the forefront of understanding the function of secreted effectors
      in eukaryotic pathogens and describe the expected spin-offs for closely related
      species exploiting comparative genomics approaches.

PMID- 19400642
TI  - Fatty Acid-derived signals in plant defense.
AB  - Fatty acids (FAs) consist of long hydrophobic, often unbranched chains of
      hydrocarbons, with hydrophilic carboxylic acid groups at one end. They are an
      important source of reserve energy and essential components of membrane lipids in
      all living organisms. In plants, FA metabolic pathways play significant roles in
      pathogen defense. Historically, FAs were only assigned passive roles in plant
      defense such as biosynthetic precursors for cuticular components or the
      phytohormone jasmonic acid. However, recent discoveries demonstrate more direct
      roles for FAs and their breakdown products in inducing various modes of plant
      defenses. Both 16- and 18-carbon FAs participate in defense to modulate basal,
      effector-triggered, and systemic immunity in plants. Studies of FA metabolic
      mutants also reveal an active signaling role for the cuticle in plant defense.
      This review summarizes the current knowledge of the involvement of FAs, FA
      derived oxylipins, and enzymes catalyzing FA metabolism in plant defense.

PMID- 19400643
TI  - Recent evolution of bacterial pathogens: the gall-forming Pantoea agglomerans
      case.
AB  - Pantoea agglomerans, a widespread epiphyte and commensal bacterium, has evolved
      into an Hrp-dependent and host-specific tumorigenic pathogen by acquiring a
      plasmid containing a pathogenicity island (PAI). The PAI was evolved on an iteron
      plasmid of the IncN family, which is distributed among genetically diverse
      populations of P. agglomerans. The structure of the PAI supports the premise of a
      recently evolved pathogen. This review offers insight into a unique model for
      emergence of new bacterial pathogens. It illustrates how horizontal gene transfer
      was the major driving force in the creation of the PAI, although a pathoadaptive
      mechanism might also be involved. It describes the crucial function of plant
      produced indole-3-acetic acid (IAA) and cytokinines (CK) in gall initiation as
      opposed to the significant but secondary role of pathogen-secreted phytohormones.
      It also unveils the role of type III effectors in determination of host
      specificity and evolution of the pathogen into pathovars. Finally, it describes
      how interactions between the quorum sensing system, hrp regulatory genes, and
      bacterially secreted IAA or CKs affect gall formation and epiphytic fitness.

PMID- 19400644
TI  - Durability of resistance in tomato and pepper to xanthomonads causing bacterial
      spot.
AB  - Both hypersensitive and quantitative forms of resistance to the bacterial spot
      pathogens (Xanthomonas spp.) occur in pepper and tomato. Five resistance genes
      involved in hypersensitivity in pepper and four in tomato have been identified so
      far. The corresponding pathogen avirulence genes have been cloned and
      characterized, and features, including a propensity for accumulating mutations
      and at times, loss of plasmid-borne avirulence genes, are known to occur. The
      frequency of these changes affects race composition among pathogen populations
      and determines the durability of the corresponding plant resistance. At least
      four different species of Xanthomonas are known to cause bacterial spot, and
      these can differ in specific avirulence gene content. Quantitative or multigenic
      resistance has also more recently been researched and appears to be more durable
      than the hypersensitive resistance. Two recessive genes have been identified that
      yield a nonhypersensitive form of resistance in pepper and together can provide
      strong resistance. More emphasis is being given to transfer of quantitative trait
      resistance to commercial cultivars of both tomato and pepper.

PMID- 19400645
TI  - Hordeivirus replication, movement, and pathogenesis.
AB  - The last Hordeivirus review appearing in this series 20 years ago focused on the
      comparative biology, relationships, and genome organization of members of the
      genus ( 68 ). Prior to the 1989 review, useful findings about the origin, disease
      occurrence, host ranges, and general biological properties of Barley stripe
      mosaic virus (BSMV) were summarized in three comprehensive reviews ( 26, 67, 107
      ). Several recent reviews emphasizing contemporary molecular genetic findings
      also may be of interest to various readers ( 15, 37, 42, 69, 70, 88, 113 ). In
      the current review, we briefly reiterate the biological properties of the four
      members of the Hordeivirus genus and describe advances in our understanding of
      organization and expression of the viral genomes. We also discuss the infection
      processes and pathogenesis of the most extensively characterized Hordeiviruses
      and frame these advances in the broader context of viruses in other families that
      have encoded triple gene block proteins. In addition, an overview of recent
      advances in the use of BSMV for virus-induced gene silencing is presented.

PMID- 19400646
TI  - Quantitative disease resistance and quantitative resistance Loci in breeding.
AB  - Quantitative disease resistance (QDR) has been observed within many crop plants
      but is not as well understood as qualitative (monogenic) disease resistance and
      has not been used as extensively in breeding. Mapping quantitative trait loci
      (QTLs) is a powerful tool for genetic dissection of QDR. DNA markers tightly
      linked to quantitative resistance loci (QRLs) controlling QDR can be used for
      marker-assisted selection (MAS) to incorporate these valuable traits. QDR confers
      a reduction, rather than lack, of disease and has diverse biological and
      molecular bases as revealed by cloning of QRLs and identification of the
      candidate gene(s) underlying QRLs. Increasing our biological knowledge of QDR and
      QRLs will enhance understanding of how QDR differs from qualitative resistance
      and provide the necessary information to better deploy these resources in
      breeding. Application of MAS for QRLs in breeding for QDR to diverse pathogens is
      illustrated by examples from wheat, barley, common bean, tomato, and pepper.
      Strategies for optimum deployment of QRLs require research to understand effects
      of QDR on pathogen populations over time.

PMID- 19400647
TI  - Migratory plant endoparasitic nematodes: a group rich in contrasts and
      divergence.
AB  - Species of migratory plant endoparasitic nematodes of three nematode families,
      Pratylenchidae, Anguinidae, and Aphelenchoididae, show marked variation in life
      cycles and fascinating contrasts in host-parasite interactions. The necessity for
      survival for periods in the absence of a host has resulted in some remarkable
      behavioral and physiological adaptations, especially in relation to anhydrobiotic
      survival. Many species are of major economic importance, and interactions with
      other pathogens enhance crop damage and yield loss. No single management strategy
      for endoparasitic nematodes is possible because control options have to be
      tailored to the nematode species, crop type, location, and economic returns. In
      this review, we focus on the contrast in life cycles and the wide spectrum of
      adaptations to obligate parasitism of most species of plant endoparasitic
      nematodes and examine how these aspects impinge on management options.

PMID- 19400648
TI  - Seed pathology progress in academia and industry.
AB  - Seed pathology involves the study and management of diseases affecting seed
      production and utilization, as well as disease management practices applied to
      seeds. In this paper, three aspects of seed pathology are discussed: research
      innovations in detection of seedborne pathogens and elucidation of their
      epidemiology; advances in development and use of seed treatments; and progress
      toward standardization of phytosanitary regulations and seed health testing
      methods. The application of nucleic-acid based detection methods in seed health
      testing has been facilitated by integrating conventional or real-time PCR with
      other technologies (e.g., BIO-PCR, IMS-PCR, MCH-PCR). PCR-based methods and
      pathogen marker technologies are being applied to epidemiological research on
      seedborne pathogens, e.g., seed transmission mechanisms, the influence of
      external biotic and abiotic factors on seed transmission, and tracking progress
      of seed-transmitted pathogens. Seed treatment use is discussed in terms of the
      revolutionary expansion in seed-applied insecticide use, impacts of new fungicide
      active ingredients, and the effects of some seed treatments on crop physiology.
      International seed trade has been affected significantly by changing
      phytosanitary regulations, not always based on science. Efforts are underway to
      revise phytosanitary regulations to reflect pest risk analysis outcomes and to
      develop standards for seed health testing methods that facilitate safe and
      efficient international trade in seeds.

PMID- 19400649
TI  - RNAi and functional genomics in plant parasitic nematodes.
AB  - Plant nematology is currently undergoing a revolution with the availability of
      the first genome sequences as well as comprehensive expressed sequence tag (EST)
      libraries from a range of nematode species. Several strategies are being used to
      exploit this wealth of information. Comparative genomics is being used to explore
      the acquisition of novel genes associated with parasitic lifestyles. Functional
      analyses of nematode genes are moving toward larger scale studies including
      global transcriptome profiling. RNA interference (RNAi) has been shown to reduce
      expression of a range of plant parasitic nematode genes and is a powerful tool
      for functional analysis of nematode genes. RNAi-mediated suppression of genes
      essential for nematode development, survival, or parasitism is revealing new
      targets for nematode control. Plant nematology in the genomics era is now facing
      the challenge to develop RNAi screens adequate for high-throughput functional
      analyses.

PMID- 19400650
TI  - Bacterial/Fungal interactions: from pathogens to mutualistic endosymbionts.
AB  - A fundamental issue in biology is the question of how bacteria initiate and
      maintain pathogenic relationships with eukaryotic hosts. Despite billions of
      years of coexistence, far less is known about bacterial/fungal interactions than
      the equivalent associations formed by either of these types of microorganisms
      with higher eukaryotes. This review highlights recent research advances in the
      field of bacterial/fungal interactions, and provides examples of the various
      forms such interactions may assume, ranging from simple antagonism and parasitism
      to more intimate associations of pathogenesis and endosymbiosis. Information
      derived from the associations of bacteria and fungi in the context of natural and
      agronomic ecosystems is emphasized, including interactions observed from
      biological control systems, endosymbiotic relationships, diseases of cultivated
      mushrooms, and model systems that expand our understanding of human disease. The
      benefits of studying these systems at the molecular level are also emphasized.

PMID- 19400651
TI  - Plant pathology: a story about biology.
AB  - Disease is a universal feature of life for multicellular organisms, and the study
      of disease has contributed to the establishment of key concepts in the biological
      sciences. This implies strong connections between plant pathology and basic
      biology, something that could perhaps be made more apparent to undergraduate
      students interested in the life sciences. To that end, we present an
      instructional narrative that begins with a simple question: Why are there
      diseases? Responses and follow-up questions can facilitate exploration of such
      topics as the evolution of parasitism, plant adaptations to parasitism, impacts
      of parasites on native plant communities, and ways in which human intervention
      can foster the emergence of aggressive plant pathogens. This approach may help to
      attract students who would not have found their way to plant pathology through
      traditional pathways. Packaging the narrative as a game may render it more
      interesting and accessible, particularly to a younger audience.

PMID- 19400653
TI  - Salicylic Acid, a multifaceted hormone to combat disease.
AB  - For more than 200 years, the plant hormone salicylic acid (SA) has been studied
      for its medicinal use in humans. However, its extensive signaling role in plants,
      particularly in defense against pathogens, has only become evident during the
      past 20 years. This review surveys how SA in plants regulates both local disease
      resistance mechanisms, including host cell death and defense gene expression, and
      systemic acquired resistance (SAR). Genetic studies reveal an increasingly
      complex network of proteins required for SA-mediated defense signaling, and this
      process is amplified by several regulatory feedback loops. The interaction
      between the SA signaling pathway and those regulated by other plant hormones
      and/or defense signals is also discussed.

PMID- 19400655
TI  - Transport pathways in biological membranes.

PMID- 19400656
TI  - ION transport by mammalian small intestine.

PMID- 19400657
TI  - Reflex and central mechanisms involved in the control of the heart and
      circulation.

PMID- 19400658
TI  - Hemodynamics.

PMID- 19400659
TI  - Heart: electrophysiology.

PMID- 19400660
TI  - Circulation in invertebrates.

PMID- 19400662
TI  - Lung metabolism and biochemistry.

PMID- 19400661
TI  - Fetal and neonatal circulation and respiration.

PMID- 19400663
TI  - Thermoreceptors.

PMID- 19400664
TI  - Inductive functions of the nervous system.

PMID- 19400665
TI  - The male reproductive system.

PMID- 19400666
TI  - Endocrine function of the pancreas.

PMID- 19400667
TI  - Calcium and phosphate metabolism.

PMID- 19400668
TI  - Prostaglandins in reproduction.

PMID- 19400669
TI  - Relationship between carbohydrate and lipid metabolism and the energy balance of
      heart muscle.

PMID- 19400670
TI  - Striated muscle.

PMID- 19400671
TI  - Smooth muscle.

PMID- 19400673
TI  - Detection of a weak somatosensory stimulus: role of the prestimulus mu rhythm and
      its top-down modulation.
AB  - The ongoing neural activity in human primary somatosensory cortex (SI) is
      characterized by field potential oscillations in the 7-13 Hz range known as the
      mu rhythm. Recent work has shown that the magnitude of the mu oscillation
      immediately preceding the onset of a weak stimulus has a significant impact on
      its detection. The neural mechanisms mediating this impact remain not well
      understood. In particular, whether and how somatosensory mu rhythm is modulated
      by executive areas prior to stimulus onset for improved behavioral performance
      has not been investigated. We addressed these issues by recording 128-channel
      scalp electroencephalogram from normal volunteers performing a somatosensory
      perception experiment in which they reported the detection of a near-threshold
      electrical stimulus ( approximately 50% detection rate) delivered to the right
      index finger. Three results were found. First, consistent with numerous previous
      reports, the N1 component ( approximately 140 msec) of the somatosensory-evoked
      potential was significantly enhanced for perceived stimulus compared to
      unperceived stimulus. Second, the prestimulus mu power and the evoked N1
      amplitude exhibited an inverted-U relationship, suggesting that an intermediate
      level of prestimulus mu oscillatory activity is conducive to stimulus processing
      and perception. Third, a Granger causality analysis revealed that the prestimulus
      causal influence in the mu band from prefrontal cortex to SI was significantly
      higher for perceived stimulus than for unperceived stimulus, indicating that
      frontal executive structures, via ongoing mu oscillations, exert cognitive
      control over posterior sensory cortices to facilitate somatosensory processing.

PMID- 19400672
TI  - The role of right and left parietal lobes in the conceptual processing of
      numbers.
AB  - Neuropsychological and functional imaging studies have associated the conceptual
      processing of numbers with bilateral parietal regions (including intraparietal
      sulcus). However, the processes driving these effects remain unclear because both
      left and right posterior parietal regions are activated by many other conceptual,
      perceptual, attention, and response-selection processes. To dissociate parietal
      activation that is number-selective from parietal activation related to other
      stimulus or response-selection processes, we used fMRI to compare numbers and
      object names during exactly the same conceptual and perceptual tasks while
      factoring out activations correlating with response times. We found that right
      parietal activation was higher for conceptual decisions on numbers relative to
      the same tasks on object names, even when response time effects were fully
      factored out. In contrast, left parietal activation for numbers was equally
      involved in conceptual processing of object names. We suggest that left parietal
      activation for numbers reflects a range of processes, including the retrieval of
      learnt facts that are also involved in conceptual decisions on object names. In
      contrast, number selectivity in right parietal cortex reflects processes that are
      more involved in conceptual decisions on numbers than object names. Our results
      generate a new set of hypotheses that have implications for the design of future
      behavioral and functional imaging studies of patients with left and right
      parietal damage.

PMID- 19400674
TI  - Mechanisms and dynamics of cortical motor inhibition in the stop-signal paradigm:
      a TMS study.
AB  - The ability to stop ongoing motor responses in a split-second is a vital element
      of human cognitive control and flexibility that relies in large part on
      prefrontal cortex. We used the stop-signal paradigm to elucidate the engagement
      of primary motor cortex (M1) in inhibiting an ongoing voluntary motor response.
      The stop-signal paradigm taps the ability to flexibly countermand ongoing
      voluntary behavior upon presentation of a stop signal. We applied single-pulse
      TMS to M1 at several intervals following the stop signal to track the time course
      of excitability of the motor system related to generating and stopping a manual
      response. Electromyography recorded from the flexor pollicis brevis allowed
      quantification of the excitability of the corticospinal tract and the involvement
      of intracortical GABA(B)ergic circuits within M1, indexed respectively by the
      amplitude of the motor-evoked potential and the duration of the late part of the
      cortical silent period (SP). The results extend our knowledge of the neural basis
      of inhibitory control in three ways. First, the results revealed a dynamic
      interplay between response activation and stopping processes at M1 level during
      stop-signal inhibition of an ongoing response. Second, increased excitability of
      inhibitory interneurons that drives SP prolongation was evident as early as 134
      msec following the instruction to stop. Third, this pattern was followed by a
      stop-related reduction of corticospinal excitability implemented around 180 after
      the stop signal. These findings point to the recruitment of GABA(B)ergic
      intracortical inhibitory circuits within M1 in stop-signal inhibition and support
      the notion of stopping as an active act of control.

PMID- 19400675
TI  - Individual differences in face cognition: brain-behavior relationships.
AB  - Individual differences in perceiving, learning, and recognizing faces, summarized
      under the term face cognition, have been shown on the behavioral and brain level,
      but connections between these levels have rarely been made. We used ERPs in
      structural equation models to determine the contributions of neurocognitive
      processes to individual differences in the accuracy and speed of face cognition
      as established by Wilhelm, Herzmann, Kunina, Danthiir, Schacht, and Sommer
      [Individual differences in face cognition, in press]. For 85 participants, we
      measured several ERP components and, in independent tasks and sessions, assessed
      face cognition abilities and other cognitive abilities, including immediate and
      delayed memory, mental speed, general cognitive ability, and object cognition.
      Individual differences in face cognition were unrelated to domain-general visual
      processes (P100) and to processes involved with memory encoding (Dm component).
      The ability of face cognition accuracy was moderately related to neurocognitive
      indicators of structural face encoding (latency of the N170) and of activating
      representations of both faces and person-related knowledge (latencies and
      amplitudes of the early and late repetition effects, ERE/N250 and LRE/N400,
      respectively). The ability of face cognition speed was moderately related to the
      amplitudes of the ERE and LRE. Thus, a substantial part of individual differences
      in face cognition is explained by the speed and efficiency of activating memory
      representations of faces and person-related knowledge. These relationships are
      not moderated by individual differences in established cognitive abilities.

PMID- 19400677
TI  - Remember the source: dissociating frontal and parietal contributions to episodic
      memory.
AB  - Event-related fMRI studies reveal that episodic memory retrieval modulates
      lateral and medial parietal cortices, dorsal middle frontal gyrus (MFG), and
      anterior PFC. These regions respond more for recognized old than correctly
      rejected new words, suggesting a neural correlate of retrieval success. Despite
      significant efforts examining retrieval success regions, their role in retrieval
      remains largely unknown. Here we asked the question, to what degree are the
      regions performing memory-specific operations? And if so, are they all equally
      sensitive to successful retrieval, or are other factors such as error detection
      also implicated? We investigated this question by testing whether activity in
      retrieval success regions was associated with task-specific contingencies (i.e.,
      perceived targetness) or mnemonic relevance (e.g., retrieval of source context).
      To do this, we used a source memory task that required discrimination between
      remembered targets and remembered nontargets. For a given region, the modulation
      of neural activity by a situational factor such as target status would suggest a
      more domain-general role; similarly, modulations of activity linked to error
      detection would suggest a role in monitoring and control rather than the
      accumulation of evidence from memory per se. We found that parietal retrieval
      success regions exhibited greater activity for items receiving correct than
      incorrect source responses, whereas frontal retrieval success regions were most
      active on error trials, suggesting that posterior regions signal successful
      retrieval whereas frontal regions monitor retrieval outcome. In addition,
      perceived targetness failed to modulate fMRI activity in any retrieval success
      region, suggesting that these regions are retrieval specific. We discuss the
      different functions that these regions may support and propose an accumulator
      model that captures the different pattern of responses seen in frontal and
      parietal retrieval success regions.

PMID- 19400676
TI  - Neural dynamics associated with semantic and episodic memory for faces: evidence
      from multiple frequency bands.
AB  - Prior semantic knowledge facilitates episodic recognition memory for faces. To
      examine the neural manifestation of the interplay between semantic and episodic
      memory, we investigated neuroelectric dynamics during the creation (study) and
      the retrieval (test) of episodic memories for famous and nonfamous faces.
      Episodic memory effects were evident in several EEG frequency bands: theta (4-8
      Hz), alpha (9-13 Hz), and gamma (40-100 Hz). Activity in these bands was
      differentially modulated by preexisting semantic knowledge and by episodic
      memory, implicating their different functional roles in memory. More
      specifically, theta activity and alpha suppression were larger for old compared
      to new faces at test regardless of fame, but were both larger for famous faces
      during study. This pattern of selective semantic effects suggests that the theta
      and alpha responses, which are primarily associated with episodic memory, reflect
      utilization of semantic information only when it is beneficial for task
      performance. In contrast, gamma activity decreased between the first (study) and
      second (test) presentation of a face, but overall was larger for famous than
      nonfamous faces. Hence, the gamma rhythm seems to be primarily related to
      activation of preexisting neural representations that may contribute to the
      formation of new episodic traces. Taken together, these data provide new insights
      into the complex interaction between semantic and episodic memory for faces and
      the neural dynamics associated with mnemonic processes.

PMID- 19400678
TI  - Prefrontal control of familiarity and recollection in working memory.
AB  - Left inferior frontal gyrus (IFG) is a critical neural substrate for the
      resolution of proactive interference (PI) in working memory. We hypothesized that
      left IFG achieves this by controlling the influence of familiarity- versus
      recollection-based information about memory probes. Consistent with this idea, we
      observed evidence for an early (200 msec)-peaking signal corresponding to memory
      probe familiarity and a late (500 msec)-resolving signal corresponding to full
      accrual of trial-related contextual ("recollection-based") information. Next, we
      applied brief trains of repetitive transcranial magnetic stimulation (rTMS) time
      locked to these mnemonic signals, to left IFG and to a control region. Only early
      rTMS of left IFG produced a modulation of the false alarm rate for high-PI
      probes. Additionally, the magnitude of this effect was predicted by individual
      differences in susceptibility to PI. These results suggest that left IFG-based
      control may bias the influence of familiarity- and recollection-based signals on
      recognition decisions.

PMID- 19400680
TI  - Detecting novelty and significance.
AB  - Studies of cognition often use an "oddball" paradigm to study effects of stimulus
      novelty and significance on information processing. However, an oddball tends to
      be perceptually more novel than the standard, repeated stimulus as well as more
      relevant to the ongoing task, making it difficult to disentangle effects due to
      perceptual novelty and stimulus significance. In the current study, effects of
      perceptual novelty and significance on ERPs were assessed in a passive viewing
      context by presenting repeated and novel pictures (natural scenes) that either
      signaled significant information regarding the current context or not. A fronto
      central N2 component was primarily affected by perceptual novelty, whereas a
      centro-parietal P3 component was modulated by both stimulus significance and
      novelty. The data support an interpretation that the N2 reflects perceptual
      fluency and is attenuated when a current stimulus matches an active memory
      representation and that the amplitude of the P3 reflects stimulus meaning and
      significance.

PMID- 19400679
TI  - The neural bases of distraction and reappraisal.
AB  - Distraction and reappraisal are two commonly used forms of cognitive emotion
      regulation. Functional neuroimaging studies have shown that each one depends upon
      interactions between pFC, interpreted as implementing cognitive control, and
      limbic regions, interpreted as mediating emotional responses. However, no study
      has directly compared distraction with reappraisal, and it remains unclear
      whether they draw upon different neural mechanisms and have different emotional
      consequences. The present fMRI study compared distraction and reappraisal and
      found both similarities and differences between the two forms of emotion
      regulation. Both resulted in decreased negative affect, decreased activation in
      the amygdala, and increased activation in prefrontal and cingulate regions.
      Relative to distraction, reappraisal led to greater decreases in negative affect
      and to greater increases in a network of regions associated with processing
      affective meaning (medial prefrontal and anterior temporal cortices). Relative to
      reappraisal, distraction led to greater decreases in amygdala activation and to
      greater increases in activation in prefrontal and parietal regions. Taken
      together, these data suggest that distraction and reappraisal differentially
      engage neural systems involved in attentional deployment and cognitive reframing
      and have different emotional consequences.

PMID- 19400681
TI  - Specific and nonspecific neural activity during selective processing of visual
      representations in working memory.
AB  - In this fMRI study, we investigated prefrontal cortex (PFC) and visual
      association regions during selective information processing. We recorded
      behavioral responses and neural activity during a delayed recognition task with a
      cue presented during the delay period. A specific cue ("Face" or "Scene") was
      used to indicate which one of the two initially viewed pictures of a face and a
      scene would be tested at the end of a trial, whereas a nonspecific cue ("Both")
      was used as control. As expected, the specific cues facilitated behavioral
      performance (faster response times) compared to the nonspecific cue. A
      postexperiment memory test showed that the items cued to remember were better
      recognized than those not cued. The fMRI results showed largely overlapped
      activations across the three cue conditions in dorsolateral and ventrolateral
      PFC, dorsomedial PFC, posterior parietal cortex, ventral occipito-temporal
      cortex, dorsal striatum, and pulvinar nucleus. Among those regions, dorsomedial
      PFC and inferior occipital gyrus remained active during the entire postcue delay
      period. Differential activity was mainly found in the association cortices. In
      particular, the parahippocampal area and posterior superior parietal lobe showed
      significantly enhanced activity during the postcue period of the scene condition
      relative to the Face and Both conditions. No regions showed differentially
      greater responses to the face cue. Our findings suggest that a better
      representation of visual information in working memory may depend on enhancing
      the more specialized visual association areas or their interaction with PFC.

PMID- 19400682
TI  - Bending the rules: strategic behavioral differences are reflected in the brain.
AB  - The implementation of higher-order conditional motor behavior was investigated in
      the present fMRI study with the objective of answering three questions: (a) what
      happens in situations where one stimulus dimension alone does not sufficiently
      determine the correct response?; (b) does the implementation of second-order
      stimulus-response (S-R) rules on the basis of matching (congruent) or nonmatching
      (incongruent) S-R associations differ from the implementation of congruent and
      incongruent first-order S-R rules?; and (c) is the cerebral implementation of
      second-order rules influenced by interindividual behavioral differences arising
      from the use of different strategies? The findings indicate that several cortical
      areas were more strongly engaged for second-order rules. More specifically, rule
      integration based on a rule match led to enhanced activation in posterior
      parietal cortex, whereas rule integration based on a rule mismatch was associated
      with enhanced activation in dorsal premotor cortex and left rostrolateral
      prefrontal cortex. Interindividual strategy differences were revealed by
      strikingly different behavioral data patterns: One subgroup of participants
      displayed strong congruency effects for second-order rules, whereas another
      subgroup displayed nonsignificant or even reversed congruency effects.
      Importantly, these strategy differences strongly modulated the cerebral
      implementation of second-order rules based on a rule mismatch. Together, the
      present findings reveal differential brain activation patterns for higher-order S
      R rules depending on rule congruency and interindividual strategy differences.
      Moreover, they emphasize the necessity of taking interindividual behavioral
      differences into account when investigating the cerebral implementation of
      cognitive processes even in rather simple and well-controlled experimental
      paradigms.

PMID- 19400683
TI  - Right-lateralized brain oscillations in human spatial navigation.
AB  - During spatial navigation, lesion and functional imaging studies suggest that the
      right hemisphere has a unique functional role. However, studies of direct human
      brain recordings have not reported interhemisphere differences in navigation
      related oscillatory activity. We investigated this apparent discrepancy using
      intracranial electroencephalographic recordings from 24 neurosurgical patients
      playing a virtual taxi driver game. When patients were virtually moving in the
      game, brain oscillations at various frequencies increased in amplitude compared
      with periods of virtual stillness. Using log-linear analysis, we analyzed the
      region and frequency specificities of this pattern and found that neocortical
      movement-related gamma oscillations (34-54 Hz) were significantly lateralized to
      the right hemisphere, especially in posterior neocortex. We also observed a
      similar right lateralization of gamma oscillations related to searching for
      objects at unknown virtual locations. Thus, our results indicate that gamma
      oscillations in the right neocortex play a special role in human spatial
      navigation.

PMID- 19400685
TI  - Availability of HIV postexposure prophylaxis services in Los Angeles County.
AB  - Postexposure prophylaxis after sexual exposure to human immunodeficiency virus
      (HIV) is recommended by state and national agencies. A cross-sectional survey of
      117 Los Angeles County sites found that 17 sites (14.5%) offer postexposure
      prophylaxis. Ten sites (8.5%) offer postexposure prophylaxis to patients who are
      uninsured. General availability of postexposure prophylaxis should be a public
      health priority.

PMID- 19400684
TI  - Spatial attention evokes similar activation patterns for visual and auditory
      stimuli.
AB  - Neuroimaging studies suggest that a fronto-parietal network is activated when we
      expect visual information to appear at a specific spatial location. Here we
      examined whether a similar network is involved for auditory stimuli. We used
      sparse fMRI to infer brain activation while participants performed analogous
      visual and auditory tasks. On some trials, participants were asked to
      discriminate the elevation of a peripheral target. On other trials, participants
      made a nonspatial judgment. We contrasted trials where the participants expected
      a peripheral spatial target to those where they were cued to expect a central
      target. Crucially, our statistical analyses were based on trials where stimuli
      were anticipated but not presented, allowing us to directly infer perceptual
      orienting independent of perceptual processing. This is the first neuroimaging
      study to use an orthogonal-cuing paradigm (with cues predicting azimuth and
      responses involving elevation discrimination). This aspect of our paradigm is
      important, as behavioral cueing effects in audition are classically only observed
      when participants are asked to make spatial judgments. We observed similar fronto
      parietal activation for both vision and audition. In a second experiment that
      controlled for stimulus properties and task difficulty, participants made spatial
      and temporal discriminations about musical instruments. We found that the pattern
      of brain activation for spatial selection of auditory stimuli was remarkably
      similar to what we found in our first experiment. Collectively, these results
      suggest that the neural mechanisms supporting spatial attention are largely
      similar across both visual and auditory modalities.

PMID- 19400686
TI  - Safety of fluoroquinolone use in patients with hepatotoxicity induced by anti
      tuberculosis regimens.
AB  - BACKGROUND: Fluoroquinolones are frequently used to replace agents in first-line
      anti-tuberculosis (anti-TB) regimens in patients with TB who have drug-induced
      hepatic dysfunction. We investigated the safety of using fluoroquinolone in an
      area where TB is endemic and where there is a high incidence of drug-induced
      liver injury. METHODS: From September 2003 through August 2006, patients who had
      aspartate aminotransferase and/or alanine aminotransferase levels >3 times the
      upper limit of normal in the presence of hepatitis symptoms or who had aspartate
      aminotransferase and/or alanine aminotransferase levels >5 times the upper limit
      of normal after receipt of anti-TB treatment were enrolled. The control group
      received ethambutol, with or without streptomycin; study groups received either
      (1) ethambutol plus levofloxacin, with or without streptomycin; or (2) ethambutol
      plus moxifloxacin, with or without streptomycin. The outcome measurement was the
      time from onset of hepatitis to normalization of liver functions. RESULTS: One
      hundred thirty-four (11.3%) of 1191 patients received a diagnosis of
      hepatotoxicity and needed to stop anti-TB treatment. The risk factor was abnormal
      baseline transaminase levels. Twenty-two of the 134 patients received the control
      medication, 40 received levofloxacin, and 45 received moxifloxacin; the remaining
      patients were excluded from the study. There were no significant prestudy
      differences between groups. Time to liver function normalization was almost the
      same for all groups (mean +/- standard deviation, 29.1+/-21.4, 25.5+/-17.6, and
      29.7+/-14.3 days, respectively). CONCLUSIONS: Abnormal baseline transaminase
      levels are the independent risk factors for anti-TB therapy-induced hepatitis.
      Levofloxacin and moxifloxacin caused no additional hepatotoxicity when they were
      used by patients with hepatitis induced by first-line anti-TB drugs.

PMID- 19400687
TI  - Risk factors for mortality among patients with nonperinatal listeriosis in Los
      Angeles County, 1992-2004.
AB  - BACKGROUND: Listeriosis is a relatively rare foodborne disease with significant
      public health implications. The causative pathogen, Listeria monocytogenes, grows
      well in refrigeration, is associated with a case-fatality rate of 20%, and causes
      an estimated 28% of all foodborne disease-related deaths. Nevertheless, data on
      the risk factors for listeriosis mortality are limited. METHODS: Using the
      passive surveillance listeriosis database of the County of Los Angeles Department
      of Public Health, we conducted a 13-year retrospective cohort study to describe
      nonperinatal listeriosis mortality in Los Angeles County during the period 1992
      2004. A nonperinatal listeriosis case was defined as one occurring in a
      nonpregnant person >42 days of age who resided in Los Angeles County and had a
      culture positive for L. monocytogenes. RESULTS: Unconditional multivariable
      logistic regression analysis of 281 nonperinatal listeriosis cases with 29 main
      effects variables resulted in finding nonhematological malignancy (odds ratio
      [OR], 5.92; 95% confidence interval [CI], 1.85-18.9), alcoholism (OR, 4.63; 95%
      CI, 1.36-15.8), age 70 years (OR, 3.44; 95% CI, 1.50-7.87), steroid medication
      (OR, 3.34; 95% CI, 1.38-8.08), and kidney disease (OR, 2.94; 95% CI, 1.18-7.31)
      to be statistically significant risk factors for mortality. Other listeriosis
      mortality risk factors with adjusted odds ratios >1.5 included blood transfusion,
      asthma, black race, Asian race, use of antibiotics, hypertension, receipt of
      chemotherapy, and Hispanic race. Patients admitted to the hospital with a
      diagnosis of sepsis alone had the highest mortality (23.7%), whereas patients
      with cases of meningitis alone had the lowest mortality (3.13%). CONCLUSIONS: The
      findings of this study should be used to help researchers and clinicians focus on
      specific risk factors to prevent nonperinatal listeriosis-related deaths.

PMID- 19400688
TI  - Short-term and medium-term clinical outcomes of quinolone-resistant Campylobacter
      infection.
AB  - BACKGROUND: Campylobacter species is a leading cause of bacterial gastroenteritis
      worldwide. Quinolone resistance has emerged as an increasing problem among
      persons with Campylobacter infection over the past decade, but the clinical
      consequences are unclear. METHODS: A case-comparison study of patients infected
      with ciprofloxacin-resistant or ciprofloxacin-susceptible Campylobacter species
      was conducted in Wales during the period 2003-2004. Campylobacter isolates were
      classified as resistant or susceptible to ciprofloxacin on the basis of
      standardized disk diffusion methods. Participants were interviewed by telephone
      at the time of illness, 3 months later, and 6 months later to compare disease
      severity, duration of illness, and medium-term clinical outcomes. RESULTS: There
      was no difference between 145 persons with ciprofloxacin-resistant infection and
      411 with ciprofloxacin-susceptible infection with regard to the severity or
      duration of acute illness. Mean duration of diarrhea was similar in patients with
      ciprofloxacin-resistant versus ciprofloxacin-susceptible infection (8.2 vs. 8.6
      days; P = .57) and did not alter significantly after adjustment for potential
      covariates, including age, underlying disease, foreign travel, use of
      antidiarrheal medication, and use of antimicrobials in a multiple linear
      regression model. There was no difference between case patients and comparison
      patients in the frequency of reported symptoms or in general practitioner
      consultation rates at either the 3-month or the 6-month follow-up interview.
      CONCLUSIONS: In this study, there was no evidence of more-severe or prolonged
      illness in participants with quinolone-resistant Campylobacter infection, nor was
      there evidence of any adverse medium-term consequences. This suggests that the
      clinical significance of quinolone resistance in Campylobacter infection may have
      been overestimated.

PMID- 19400689
TI  - Bats in the bedroom, bats in the belfry: reanalysis of the rationale for rabies
      postexposure prophylaxis.
AB  - BACKGROUND: We assessed the scientific basis and practical implications of
      recommendations made since the late 1990s to offer rabies postexposure
      prophylaxis (RPEP) for occult bat encounters, including recommendations to offer
      RPEP to persons with bedroom exposure to a bat while sleeping without evidence of
      direct physical contact. METHODS: The number needed to treat after bedroom
      exposure to a bat was calculated as the percentage of population exposed
      multiplied by the inverse of crude rabies incidence. Bedroom exposure was
      estimated in a population survey of 14,453 households. Incidence was based on
      reported human cases in Canada and the United States, 1990-2007. RESULTS: In the
      population surveyed, bedroom bat exposure while sleeping and without known
      physical contact occurred at an annual rate of 0.099%. We estimate that <5% of
      eligible persons with bedroom exposure receive RPEP as recommended. The incidence
      of human rabies due to bedroom bat exposure without recognized contact was 1 case
      per 2.7 billion person-years. The number needed to treat to prevent a single case
      of human rabies in that context ranges from 314,000 to 2.7 million persons. A
      total of 293-2500 health care professionals working full-time for a full year
      would be required to prevent a single human case of bat rabies due to bedroom
      exposure without recognized contact. Amounts of Can $228 million to Can $2.0
      billion are additionally required for associated material costs. CONCLUSIONS:
      Human rabies acquired through bedroom exposure to a bat while sleeping and
      without recognized contact is rare. Conversely, such exposures are not uncommon
      in the population, and the resources required for associated RPEP are orders of
      magnitude higher than those required for most interventions that are considered
      to be reasonable. Current RPEP recommendations related to occult bat contact
      should be reconsidered.

PMID- 19400690
TI  - Implementation of HIV testing at 2 New York City bathhouses: from pilot to
      clinical service.
AB  - BACKGROUND: Commercial sex venues (e.g., bathhouses) that cater to men who have
      sex with men (MSM) continue to function in most urban areas. These venues present
      a challenge to developing strategies to prevent the spread of the human
      immunodeficiency virus (HIV), but they also provide opportunities for
      interventions to reduce the risk and rate of disease transmission. Several cities
      in the United States have developed programs that offer HIV testing in these
      venues. Similar programs have not existed before in New York City. METHODS: A
      pilot HIV testing program was implemented at 2 New York City bathhouses. Testing
      included rapid HIV testing, the use of the serologic testing algorithm for recent
      HIV seroconversion, and pooled plasma HIV viral load to detect and date incident
      and acute HIV infections. In addition to HIV tests, behavioral and demographic
      data were collected from 493 presumed HIV-negative participants. RESULTS: The
      pilot program recruited MSM who were at high risk for HIV infection. Of the 493
      men tested, 20 (4%) were found to be positive for HIV, and 8 (40%) of these 20
      men demonstrated evidence of acute or recent HIV infection. The program tested
      men often not tested in more traditional medical settings. Significant
      disparities were demonstrated in the testing habits of MSM who reported having
      sex with women and had not disclosed same-sex activities to their caregivers.
      CONCLUSIONS: Bathhouse-based testing for HIV infection can be implemented in New
      York City and would include a population of MSM who are at high risk for HIV
      infection. Because of the high rate of recent HIV infection, expanded testing in
      these venues may be a good strategy to reduce the forward transmission of HIV in
      this highly sexually active population.

PMID- 19400691
TI  - Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma.
AB  - Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (HL) and
      lymphocytic and histiocytic (L&H) cells in nodular lymphocyte-predominant HL
      (NLPHL) are derived from germinal-center B cells. HRS cells have, however,
      largely lost their B cell phenotype and aberrantly express markers and
      transcriptional regulators of other hematolymphoid cell types. Deregulation of
      multiple signaling pathways and downstream transcription factors, including
      receptor tyrosine kinases, nuclear factor-kappa B (NF-kappaB), and Janus
      kinase/signal transducer and activator of transcription (JAK/STAT), is a further
      hallmark of HRS cells. These cells harbor genetic lesions that contribute to or
      cause increases in the activity of transcription factors of the NF-kappaB and
      STAT families. HRS cells are found within a mixed reactive cellular infiltrate
      and interact with these nonmalignant cells in a complex fashion that appears to
      be essential for HRS cell survival and proliferation. Less is known about the
      pathogenesis of L&H cells in NLPHL, but increases in the activity of receptor
      tyrosine kinases, NF-kappaB, and JAK/STAT have also been detected.

PMID- 19400692
TI  - The pathogenesis of pituitary tumors.
AB  - Recently there has been significant progress in our understanding of pituitary
      development, physiology, and pathology. New information has helped to clarify the
      classification of pituitary tumors. Epidemiologic analyses have identified a much
      higher incidence of pituitary tumors than previously thought. We review the
      pathogenetic factors that have been implicated in pituitary tumorigenesis and the
      application of novel targeted therapies that underscore the increasingly
      important role of the pathologist in determining accurate diagnoses and
      facilitating appropriate treatment of patients with these disorders.

PMID- 19400693
TI  - Serrated polyps and colorectal cancer: new pathway to malignancy.
AB  - Until recently, two major forms of colorectal epithelial polyp were recognized:
      the adenoma and the hyperplastic polyp. Adenomas were perceived to represent the
      precursor to colorectal cancer, whereas hyperplastic polyps were viewed as
      innocuous lesions with no potential for progression to malignancy. We now
      recognize, however, that the lesions formerly classified as hyperplastic actually
      represent a heterogeneous group of polyps, some of which have a significant risk
      for neoplastic transformation. These serrated polyps include not only
      hyperplastic polyps but also traditional serrated adenomas and sessile serrated
      adenomas. These polyps demonstrate characteristic molecular alterations not
      commonly seen in colorectal adenomas, and they probably progress to colorectal
      cancer by means of a new pathway: the serrated neoplasia pathway. The morphologic
      features of serrated colorectal lesions, the molecular alterations that
      characterize them, and their role in colorectal cancer development are discussed
      herein.

PMID- 19400694
TI  - Regulation of hepcidin and iron-overload disease.
AB  - Hepcidin, a 25-amino-acid antimicrobial peptide, is the central regulator of iron
      homeostasis. Hepcidin transcription is upregulated by inflammatory cytokines,
      iron, and bone morphogenetic proteins and is downregulated by iron deficiency,
      ineffective erythropoiesis, and hypoxia. The iron transporter ferroportin is the
      cognate receptor of hepcidin and is destroyed as a result of interaction with the
      peptide. Except for inherited defects of ferroportin and hepcidin itself, all
      forms of iron-storage disease appear to arise from hepcidin dysregulation.
      Studies using multiple approaches have begun to delineate the molecular
      mechanisms that regulate hepcidin expression, particularly at the transcriptional
      level. Knowledge of the regulation of hepcidin by inflammation, iron,
      erythropoiesis, and hypoxia will lead to an understanding of the pathogenesis of
      primary hemochromatosis, secondary iron overload, and anemia of inflammatory
      disease.

PMID- 19400696
TI  - Molecular pathogenesis of cutaneous melanocytic neoplasms.
AB  - Melanoma is the deadliest form of skin cancer without an effective treatment. An
      understanding of the genetic basis of melanoma has recently shed light on some of
      the mechanisms of melanomagenesis. This review explores the major genes involved
      in familial and sporadic cutaneous melanoma with an emphasis on CDKN2A, CDK4,
      MC1R, and MAPK pathway targets (e.g., RAS and BRAF), apoptosis regulators (e.g.,
      BCL-2, AKT, and APAF-1), and the tumor-suppressor genes TP53 and PTEN. New
      directions for therapeutics based on our current knowledge of the genes
      implicated in melanoma are also discussed.

PMID- 19400697
TI  - The nutritional significance of lipid rafts.
AB  - The structure, size, stability, and functionality of lipid rafts are still in
      debate, but recent techniques allowing direct visualization have characterized
      them in a wide range of cell types. Lipid rafts are potentially modifiable by
      diet, particularly (but not exclusively) by dietary fatty acids. However, it is
      not clear whether dietary polyunsaturated fatty acids (PUFAs) are incorporated
      into raft lipids or whether their low affinity to cholesterol disallows this and
      causes phase separation from rafts and displacement of raft proteins. This review
      examines the potential for dietary modification of raft structure and function in
      the immune system, brain and retinal tissue, the gut, and in cancer cells.
      Although there is increasing evidence to suggest that membrane microdomains, and
      their modulation, have an impact in health and disease, it is too early to judge
      whether modulation of lipid rafts is responsible for the immunomodulatory effects
      of n-3 PUFA. In addition to dietary fatty acids, gangliosides and cholesterol may
      also modulate microdomains in a number of tissues, and recent work has
      highlighted sphingolipids in membrane microdomains as potential targets for
      inhibition of tumor growth by n-3 PUFA. The roles of fatty acids and gangliosides
      in cognitive development, age-related cognitive decline, psychiatric disorders,
      and Alzheimer's disease are poorly understood and require clarification,
      particularly with respect to the contribution of lipid rafts. The roles of lipid
      rafts in cancer, in microbial pathogenesis, and in insulin resistance are only
      just emerging, but compelling evidence indicates the growing importance of
      membrane microdomains in health and disease.

PMID- 19400698
TI  - Use of phosphatide precursors to promote synaptogenesis.
AB  - New brain synapses form when a postsynaptic structure, the dendritic spine,
      interacts with a presynaptic terminal. Brain synapses and dendritic spines,
      membrane-rich structures, are depleted in Alzheimer's disease, as are some
      circulating compounds needed for synthesizing phosphatides, the major
      constituents of synaptic membranes. Animals given three of these compounds, all
      nutrients-uridine, the omega-3 polyunsaturated fatty acid docosahexaenoic acid,
      and choline-develop increased levels of brain phosphatides and of proteins that
      are concentrated within synaptic membranes (e.g., PSD-95, synapsin-1), improved
      cognition, and enhanced neurotransmitter release. The nutrients work by
      increasing the substrate-saturation of low-affinity enzymes that synthesize the
      phosphatides. Moreover, uridine and its nucleotide metabolites activate brain P2Y
      receptors, which control neuronal differentiation and synaptic protein synthesis.
      A preparation containing these compounds is being tested for treating Alzheimer's
      disease.

PMID- 19400699
TI  - Vitamin D gene pathway polymorphisms and risk of colorectal, breast, and prostate
      cancer.
AB  - Higher vitamin D exposure is hypothesized to prevent several cancers, possibly
      through genomic effects modulated by the vitamin D receptor (VDR), and
      autocrine/paracrine metabolism of the VDR's ligand, 1alpha,25-(OH)(2)-vitamin D.
      Herein we review the background and evidence to date on associations between
      polymorphisms in VDR and selected genes in the vitamin D pathway in relation to
      colorectal, breast, and prostate cancer. Although most studies to date have
      examined only a few VDR polymorphisms, more are beginning to comprehensively
      investigate polymorphisms in the VDR as well as in other vitamin D pathway genes,
      such as the vitamin D-binding protein gene (Gc) and CYP27B1 and CYP24A1, which
      code for enzymes that, respectively, synthesize and degrade 1alpha,25-(OH)(2)
      vitamin D. Currently, there is no strong, consistent epidemiologic evidence for
      substantial influences of single variants in vitamin D pathway genes on risk for
      colorectal, breast, or prostate cancer, but promising leads are developing.

PMID- 19400695
TI  - The brainstem and serotonin in the sudden infant death syndrome.
AB  - The sudden infant death syndrome (SIDS) is the sudden death of an infant under
      one year of age that is typically associated with sleep and that remains
      unexplained after a complete autopsy and death scene investigation. A leading
      hypothesis about its pathogenesis is that many cases result from defects in
      brainstem-mediated protective responses to homeostatic stressors occurring during
      sleep in a critical developmental period. Here we review the evidence for the
      brainstem hypothesis in SIDS with a focus upon abnormalities related to the
      neurotransmitter serotonin in the medulla oblongata, as these are the most robust
      pathologic findings to date. In this context, we synthesize the human autopsy
      data with genetic, whole-animal, and cellular data concerning the function and
      development of the medullary serotonergic system. These emerging data suggest an
      important underlying mechanism in SIDS that may help lead to identification of
      infants at risk and specific interventions to prevent death.

PMID- 19400701
TI  - Functional significance of zinc-related signaling pathways in immune cells.
AB  - Recent years have brought a paradigm shift for the role of the essential trace
      element zinc in immunity. Although its function as a structural component of many
      enzymes has been known for decades, current experimental evidence points to an
      additional function of the concentration of free or loosely bound zinc ions as an
      intracellular signal. The activity of virtually all immune cells is modulated by
      zinc in vitro and in vivo. In this review, we discuss the interactions of zinc
      with major signaling pathways that regulate immune cell activity, and the
      implications of zinc deficiency or supplementation on zinc signaling as the
      molecular basis for an effect of zinc on immune cell function.

PMID- 19400702
TI  - From tryptophan to hydroxytryptophan: reflections on a busy life.
AB  - Given the very difficult odyssey of my early years, who could have imagined the
      incredible and successful journey that constituted my life path after age 13? I
      was born into a Jewish family in Breslau, Germany, right before the rise of
      Nazism and Hitler's election. After Kristallnacht, when my father was taken to
      Buchenwald Concentration Camp, we had to leave Germany as soon as possible. The
      first opportunity came in May of 1939, when we boarded the SS St. Louis bound for
      Havana, Cuba. Almost all passengers were denied entrance into Cuba, and the ship
      had to go back to Europe, where I ended up in France. In December of 1939, during
      World War II, I was fortunate to be able to leave France. This time I made it to
      Cuba, where my father was already in residence. A year later, my entire family
      was allowed into the United States. I took advantage of all the educational
      resources in this land of opportunity. I graduated valedictorian of my high
      school class and earned a four-year scholarship to Rutgers University, where I
      obtained a Bachelor of Science degree. I went on to earn a Master's degree from
      the University of Connecticut and finally a PhD from the University of Illinois.
      Within two months after graduating from Illinois, I was hired as an assistant
      professor of nutritional biochemistry at Rutgers, where I enjoyed a most
      productive research and teaching career. My PhD research involved tryptophan and
      niacin metabolism in the chick, and upon arrival at Rutgers I continued amino
      acid studies with the goal of assessing the essential amino acid requirements for
      egg production. This research was crowned with success and was followed with
      amino acid requirement studies for maintenance and for growth in rabbits, and
      ultimately with a reevaluation of requirements in adult humans. An outgrowth of
      the maintenance requirements led to a series of investigations into the
      metabolism of histidine, histamine, and carnosine (a histidine-containing
      dipeptide). Histamine, we found, plays an important role in wound healing and
      stress management. Pyridoxal phosphate is the cofactor for the enzyme histidine
      decarboxylase required for histamine synthesis and similarly serves as a cofactor
      for hydroxytryptophan decarboxylase, the enzyme that is part of the pathway to
      serotonin synthesis. Investigations into these pathways led to interesting
      findings: brain concentrations of serotonin could be increased by supplementing
      the diet of rats with tryptophan and pyridoxine; the elevated brain serotonin
      levels had behavioral consequences. Alcohol craving, addiction, and withdrawal
      symptoms are affected by serotonin concentrations in the brain, and alleviation
      of these conditions can be achieved with simultaneous administration of serotonin
      and dopamine agonists. In the midst of our early amino acid studies, we
      serendipitously also became involved with lipid metabolism in relation to
      atherosclerosis and blood cholesterol in a chicken model. This work led to the
      recognition that soluble fibers, like pectin, had strong cholesterol-lowering
      properties that were beneficial in lowering the incidence of coronary plaque
      formation. The research success that I have enjoyed has been coupled with the
      gift of three accomplished children who are making important contributions as
      professionals in their fields of endeavor. My wife and I are also blessed with 10
      wonderful grandchildren, our pride and joy!

PMID- 19400700
TI  - Is there a fatty acid taste?
AB  - Taste is a chemical sense that aids in the detection of nutrients and guides food
      choice. A limited number of primary qualities comprise taste. Accumulating
      evidence has raised a question about whether fat should be among them. Most
      evidence indicates triacylglycerol is not an effective taste stimulus, though it
      clearly contributes sensory properties to foods by carrying flavor compounds and
      altering texture. However, there is increasing anatomical, electrophysiological,
      animal behavior, imaging, metabolic, and psychophysical evidence that free fatty
      acids are detectable when non-taste cues are minimized. Free fatty acids varying
      in saturation and chain length are detectable, suggesting the presence of
      multiple transduction mechanisms and/or a nonspecific mechanism in the oral
      cavity. However, confirmation of "fatty" as a taste primary will require
      additional studies that verify these observations are taste specific. Oral
      exposure to free fatty acids likely serves as a warning signal to discourage
      intake and influences lipid metabolism.

PMID- 19400703
TI  - Genetic variation and effects on human eating behavior.
AB  - Feeding is a physiological process, influenced by genetic factors and the
      environment. In recent years, many studies have been performed to unravel the
      involvement of genetics in both eating behavior and its pathological forms:
      eating disorders and obesity. In this review, we provide a condensed introduction
      on the neurological aspects of eating and we describe the current status of
      research into the genetics of eating behavior, primarily focused on specific
      traits such as taste, satiation, and hunger. This is followed by an overview on
      the genetic studies done to unravel the heritable background of obesity and
      eating disorders. We examine the discussion currently taking place in the field
      of genetics of complex disorders and phenotypes on how to perform good and
      powerful studies, with the use of large-scale whole-genome association studies as
      one of the possible solutions. In the final part of this review, we give our view
      on the latest developments, including endophenotype approaches and animal
      studies. Studies of endophenotypes of eating behavior may help to identify core
      traits that are genetically influenced. Such studies would yield important
      knowledge on the underlying biological scaffold on which diagnostic criteria for
      eating disorders could be based and would provide information to influence eating
      behavior toward healthier living.

PMID- 19400704
TI  - Roles for vitamin K beyond coagulation.
AB  - Recent interest in vitamin K has been motivated by evidence of physiological
      roles beyond that of coagulation. Vitamin K and vitamin K-dependent (VKD)
      proteins may be involved in regulation of calcification, energy metabolism, and
      inflammation. However, the evidence for many of these proposed roles in the
      maintenance of health is equivocal. There is also an emerging viewpoint that the
      biochemical function of vitamin K may extend beyond that of a cofactor for the
      VKD carboxylation of glutamyl residues (Glus) to carboxylated Glus in VKD
      proteins.

PMID- 19400705
TI  - Proteomics by mass spectrometry: approaches, advances, and applications.
AB  - Mass spectrometry (MS) is the most comprehensive and versatile tool in large
      scale proteomics. In this review, we dissect the overall framework of the MS
      experiment into its key components. We discuss the fundamentals of proteomic
      analyses as well as recent developments in the areas of separation methods,
      instrumentation, and overall experimental design. We highlight both the inherent
      strengths and limitations of protein MS and offer a rough guide for selecting an
      experimental design based on the goals of the analysis. We emphasize the
      versatility of the Orbitrap, a novel mass analyzer that features high resolution
      (up to 150,000), high mass accuracy (2-5 ppm), a mass-to-charge range of 6000,
      and a dynamic range greater than 10(3). High mass accuracy of the Orbitrap
      expands the arsenal of the data acquisition and analysis approaches compared with
      a low-resolution instrument. We discuss various chromatographic techniques,
      including multidimensional separation and ultra-performance liquid
      chromatography. Multidimensional protein identification technology (MudPIT)
      involves a continuum sample preparation, orthogonal separations, and MS and
      software solutions. We discuss several aspects of MudPIT applications to
      quantitative phosphoproteomics. MudPIT application to large-scale analysis of
      phosphoproteins includes (a) a fractionation procedure for motif-specific
      enrichment of phosphopeptides, (b) development of informatics tools for
      interrogation and validation of shotgun phosphopeptide data, and (c) in-depth
      data analysis for simultaneous determination of protein expression and
      phosphorylation levels, analog to western blot measurements. We illustrate MudPIT
      application to quantitative phosphoproteomics of the beta adrenergic pathway. We
      discuss several biological discoveries made via mass spectrometry pipelines with
      a focus on cell signaling proteomics.

PMID- 19400707
TI  - The influence of muscle physiology and advanced technology on sports performance.
AB  - Muscle mechanical output such as force and power are governed by highly nonlinear
      intrinsic muscle properties associated with different muscle fiber types and are
      influenced by training and age. Many of the interactions between these properties
      pose trade-offs such that an individual's anthropometrics and muscle morphology
      may allow an athlete to excel in one sport but not in others. Advanced modeling
      and simulation techniques are powerful tools to gain insight into performance
      limits, optimal equipment designs, and mechanisms that may lead to injury. Recent
      technological innovations have produced faster running tracks, bicycles, speed
      skates, and swimming pools. This review discusses the influence of intrinsic
      muscle properties in sports and how advanced technology can be used to extend the
      limits of human performance.

PMID- 19400706
TI  - Patient-specific modeling of cardiovascular mechanics.
AB  - Advances in numerical methods and three-dimensional imaging techniques have
      enabled the quantification of cardiovascular mechanics in subject-specific
      anatomic and physiologic models. Patient-specific models are being used to guide
      cell culture and animal experiments and test hypotheses related to the role of
      biomechanical factors in vascular diseases. Furthermore, biomechanical models
      based on noninvasive medical imaging could provide invaluable data on the in vivo
      service environment where cardiovascular devices are employed and on the effect
      of the devices on physiologic function. Finally, patient-specific modeling has
      enabled an entirely new application of cardiovascular mechanics, namely
      predicting outcomes of alternate therapeutic interventions for individual
      patients. We review methods to create anatomic and physiologic models, obtain
      properties, assign boundary conditions, and solve the equations governing blood
      flow and vessel wall dynamics. Applications of patient-specific models of
      cardiovascular mechanics are presented, followed by a discussion of the
      challenges and opportunities that lie ahead.

PMID- 19400708
TI  - Microengineered platforms for cell mechanobiology.
AB  - Mechanical forces play important roles in the regulation of various biological
      processes at the molecular and cellular level, such as gene expression, adhesion,
      migration, and cell fate, which are essential to the maintenance of tissue
      homeostasis. In this review, we discuss emerging bioengineered tools enabled by
      microscale technologies for studying the roles of mechanical forces in cell
      biology. In addition to traditional mechanobiology experimental techniques, we
      review recent advances of microelectromechanical systems (MEMS)-based approaches
      for cell mechanobiology and discuss how microengineered platforms can be used to
      generate in vivo-like micromechanical environment in in vitro settings for
      investigating cellular processes in normal and pathophysiological contexts. These
      capabilities also have significant implications for mechanical control of cell
      and tissue development and cell-based regenerative therapies.

PMID- 19400709
TI  - Cell mechanics: dissecting the physical responses of cells to force.
AB  - It is now widely appreciated that normal tissue morphology and function rely upon
      cells' ability to sense and generate forces appropriate to their correct tissue
      context. Although the effects of forces on cells have been studied for decades,
      our understanding of how those forces propagate through and act on different cell
      substructures remains at an early stage. The past decade has seen a resurgence of
      interest, with a variety of different micromechanical methods in current use that
      probe cells' dynamic deformation in response to a time-varying force. The ability
      of researchers to carefully measure the mechanical properties of cells subjected
      to a variety of pharmacological and genetic interventions, however, currently
      outstrips our ability to quantitatively interpret the data in many cases. Despite
      these challenges, the stage is now set for the development of detailed models for
      cell deformability, motility, and mechanosensing that are rooted at the molecular
      level.

PMID- 19400710
TI  - Implanted neural interfaces: biochallenges and engineered solutions.
AB  - Neural interfaces are connections that enable two-way exchange of information
      with the nervous system. These connections can occur at multiple levels,
      including with peripheral nerves, with the spinal cord, or with the brain; in
      many instances, fundamental biophysical and biological challenges are shared
      across these levels. We review these challenges, including selectivity,
      stability, resolution versus invasiveness, implant-induced injury, and the host
      interface response. Subsequently, we review the engineered solutions to these
      challenges, including electrode designs and geometry, stimulation waveforms,
      materials, and surface modifications. Finally, we consider emerging opportunities
      to improve neural interfaces, including cellular-level silicon to neuron
      connections, optical stimulation, and approaches to control inflammation.
      Overcoming the biophysical and biological challenges will enable effective high
      density neural interfaces for stimulation and recording.

PMID- 19400711
TI  - Hypothermia therapy for brain injury.
AB  - Induced hypothermia is an acknowledged useful therapy for treating conditions
      that lead to cell and tissue damage caused by ischemia, including traumatic brain
      injury, stroke, and cardiac arrest. An accumulating body of clinical evidence,
      together with several decades of research, has documented that the efficacy of
      hypothermia is dependent on achieving a reduced temperature in the target tissue
      before or soon following the ischemia-precipitating event. The temperature must
      be lowered to within a rather small range of values to effect therapeutic benefit
      without introducing collateral problems. Rewarming must be much slower than
      cooling. Many different methods and devices have been used for cooling, with
      mixed results. There are existing opportunities for bioengineers to improve our
      understanding of the mechanisms of hypothermia and to develop more effective
      methods of cooling the brain following trauma.

PMID- 19400712
TI  - Fluorescent probes for live-cell RNA detection.
AB  - Commonly used techniques for analyzing gene expression, such as polymerase chain
      reaction (PCR), microarrays, and in situ hybridization, have proven invaluable in
      understanding RNA processing and regulation. However, these techniques rely on
      the use of lysed and/or fixed cells and are therefore limited in their ability to
      provide important spatial-temporal information. This has led to the development
      of numerous techniques for imaging RNA in living cells, some of which have
      already provided important insight into the dynamic role RNA plays in dictating
      cell behavior. Here we review the fluorescent probes that have allowed for RNA
      imaging in living cells and discuss their utility and limitations. Common
      challenges faced by fluorescent probes, such as probe design, delivery, and
      target accessibility, are also discussed. It is expected that continued
      advancements in live cell imaging of RNA will open new and exciting opportunities
      in a wide range of biological and medical applications.

PMID- 19400714
TI  - The influence of stress hormones on fear circuitry.
AB  - Fear arousal, initiated by an environmental threat, leads to activation of the
      stress response, a state of alarm that promotes an array of autonomic and
      endocrine changes designed to aid self-preservation. The stress response includes
      the release of glucocorticoids from the adrenal cortex and catecholamines from
      the adrenal medulla and sympathetic nerves. These stress hormones, in turn,
      provide feedback to the brain and influence neural structures that control
      emotion and cognition. To illustrate this influence, we focus on how it impacts
      fear conditioning, a behavioral paradigm widely used to study the neural
      mechanisms underlying the acquisition, expression, consolidation,
      reconsolidation, and extinction of emotional memories. We also discuss how stress
      and the endocrine mediators of the stress response influence the morphological
      and electrophysiological properties of neurons in brain areas that are crucial
      for fear-conditioning processes, including the amygdala, hippocampus, and
      prefrontal cortex. The information in this review illuminates the behavioral and
      cellular events that underlie the feedforward and feedback networks that mediate
      states of fear and stress and their interaction in the brain.

PMID- 19400713
TI  - The primate cortical auditory system and neural representation of conspecific
      vocalizations.
AB  - Over the past decade, renewed interest in the auditory system has resulted in a
      surge of anatomical and physiological research in the primate auditory cortex and
      its targets. Anatomical studies have delineated multiple areas in and around
      primary auditory cortex and demonstrated connectivity among these areas, as well
      as between these areas and the rest of the cortex, including prefrontal cortex.
      Physiological recordings of auditory neurons have found that species-specific
      vocalizations are useful in probing the selectivity and potential functions of
      acoustic neurons. A number of cortical regions contain neurons that are robustly
      responsive to vocalizations, and some auditory responsive neurons show more
      selectivity for vocalizations than for other complex sounds. Demonstration of
      selectivity for vocalizations has prompted the question of which features are
      encoded by higher-order auditory neurons. Results based on detailed studies of
      the structure of these vocalizations, as well as the tuning and information
      coding properties of neurons sensitive to these vocalizations, have begun to
      provide answers to this question. In future studies, these and other methods may
      help to define the way in which cells, ensembles, and brain regions process
      communication sounds. Moreover, the discovery that several nonprimary auditory
      cortical regions may be multisensory and responsive to vocalizations with
      corresponding facial gestures may change the way in which we view the processing
      of communication information by the auditory system.

PMID- 19400715
TI  - Representation of number in the brain.
AB  - Number symbols have allowed humans to develop superior mathematical skills that
      are a hallmark of technologically advanced cultures. Findings in animal
      cognition, developmental psychology, and anthropology indicate that these
      numerical skills are rooted in nonlinguistic biological primitives. Recent
      studies in human and nonhuman primates using a broad range of methodologies
      provide evidence that numerical information is represented and processed by
      regions of the prefrontal and posterior parietal lobes, with the intraparietal
      sulcus as a key node for the representation of the semantic aspect of numerical
      quantity.

PMID- 19400717
TI  - Physiology and pharmacology of striatal neurons.
AB  - The basal ganglia occupy the core of the forebrain and consist of evolutionarily
      conserved motor nuclei that form recurrent circuits critical for motivation and
      motor planning. The striatum is the main input nucleus of the basal ganglia and a
      key neural substrate for procedural learning and memory. The vast majority of
      striatal neurons are spiny GABAergic projection neurons, which exhibit slow but
      temporally precise spiking in vivo. Contributing to this precision are several
      different types of interneurons that constitute only a small fraction of total
      neuron number but play a critical role in regulating striatal output. This review
      examines the cellular physiology and modulation of striatal neurons that give
      rise to their unique properties and function.

PMID- 19400716
TI  - Axon growth and guidance: receptor regulation and signal transduction.
AB  - The development of precise connectivity patterns during the establishment of the
      nervous system depends on the regulated action of diverse, conserved families of
      guidance cues and their neuronal receptors. Determining how these signaling
      pathways function to regulate axon growth and guidance is fundamentally important
      to understanding wiring specificity in the nervous system and will undoubtedly
      shed light on many neural developmental disorders. Considerable progress has been
      made in defining the mechanisms that regulate the correct spatial and temporal
      distribution of guidance receptors and how these receptors in turn signal to the
      growth cone cytoskeleton to control steering decisions. This review focuses on
      recent advances in our understanding of the mechanisms mediating growth cone
      guidance with a particular emphasis on the control of guidance receptor
      regulation and signaling.

PMID- 19400718
TI  - Using diffusion imaging to study human connectional anatomy.
AB  - Diffusion imaging can be used to estimate the routes taken by fiber pathways
      connecting different regions of the living brain. This approach has already
      supplied novel insights into in vivo human brain anatomy. For example, by
      detecting where connection patterns change, one can define anatomical borders
      between cortical regions or subcortical nuclei in the living human brain for the
      first time. Because diffusion tractography is a relatively new technique,
      however, it is important to assess its validity critically. We discuss the degree
      to which diffusion tractography meets the requirements of a technique to assess
      structural connectivity and how its results compare to those from the gold
      standard tract tracing methods in nonhuman animals. We conclude that although
      tractography offers novel opportunities it also raises significant challenges to
      be addressed by further validation studies to define precisely the limitations
      and scope of this exciting new technique.

PMID- 19400719
TI  - The science of neural interface systems.
AB  - The ultimate goal of neural interface research is to create links between the
      nervous system and the outside world either by stimulating or by recording from
      neural tissue to treat or assist people with sensory, motor, or other
      disabilities of neural function. Although electrical stimulation systems have
      already reached widespread clinical application, neural interfaces that record
      neural signals to decipher movement intentions are only now beginning to develop
      into clinically viable systems to help paralyzed people. We begin by reviewing
      state-of-the-art research and early-stage clinical recording systems and focus on
      systems that record single-unit action potentials. We then address the potential
      for neural interface research to enhance basic scientific understanding of brain
      function by offering unique insights in neural coding and representation,
      plasticity, brain-behavior relations, and the neurobiology of disease. Finally,
      we discuss technical and scientific challenges faced by these systems before they
      are widely adopted by severely motor-disabled patients.

PMID- 19400720
TI  - The neurobiology of individual differences in complex behavioral traits.
AB  - Neuroimaging, especially BOLD fMRI, has begun to identify how variability in
      brain function contributes to individual differences in complex behavioral
      traits. In parallel, pharmacological fMRI and multimodal PET/fMRI are identifying
      how variability in molecular signaling pathways influences individual differences
      in brain function. Against this background, functional genetic polymorphisms are
      being utilized to understand the origins of variability in signaling pathways as
      well as to model efficiently how such emergent variability impacts behaviorally
      relevant brain function. This article provides an overview of a research strategy
      seeking to integrate these complementary technologies and utilizes existing
      empirical data to illustrate its effectiveness in illuminating the neurobiology
      of individual differences in complex behavioral traits. The article also
      discusses how such efforts can contribute to the identification of predictive
      markers that interact with environmental factors to precipitate disease and to
      develop more effective and individually tailored treatment regimes.

PMID- 19400722
TI  - Serotonin in affective control.
AB  - Serotonin is a neuromodulator that is extensively entangled in fundamental
      aspects of brain function and behavior. We present a computational view of its
      involvement in the control of appetitively and aversively motivated actions. We
      first describe a range of its effects in invertebrates, endowing specific
      structurally fixed networks with plasticity at multiple spatial and temporal
      scales. We then consider its rather widespread distribution in the mammalian
      brain. We argue that this is associated with a more unified representational and
      functional role in aversive processing that is amenable to computational analyses
      with the kinds of reinforcement learning techniques that have helped elucidate
      dopamine's role in appetitive behavior. Finally, we suggest that it is only a
      partial reflection of dopamine because of essential asymmetries between the
      natural statistics of rewards and punishments.

PMID- 19400721
TI  - Synaptic mechanisms for plasticity in neocortex.
AB  - Sensory experience and learning alter sensory representations in cerebral cortex.
      The synaptic mechanisms underlying sensory cortical plasticity have long been
      sought. Recent work indicates that long-term cortical plasticity is a complex,
      multicomponent process involving multiple synaptic and cellular mechanisms.
      Sensory use, disuse, and training drive long-term potentiation and depression
      (LTP and LTD), homeostatic synaptic plasticity and plasticity of intrinsic
      excitability, and structural changes including formation, removal, and
      morphological remodeling of cortical synapses and dendritic spines. Both
      excitatory and inhibitory circuits are strongly regulated by experience. This
      review summarizes these findings and proposes that these mechanisms map onto
      specific functional components of plasticity, which occur in common across the
      primary somatosensory, visual, and auditory cortices.

PMID- 19400723
TI  - Neuronal gamma-band synchronization as a fundamental process in cortical
      computation.
AB  - Neuronal gamma-band synchronization is found in many cortical areas, is induced
      by different stimuli or tasks, and is related to several cognitive capacities.
      Thus, it appears as if many different gamma-band synchronization phenomena
      subserve many different functions. I argue that gamma-band synchronization is a
      fundamental process that subserves an elemental operation of cortical
      computation. Cortical computation unfolds in the interplay between neuronal
      dynamics and structural neuronal connectivity. A core motif of neuronal
      connectivity is convergence, which brings about both selectivity and invariance
      of neuronal responses. However, those core functions can be achieved
      simultaneously only if converging neuronal inputs are functionally segmented and
      if only one segment is selected at a time. This segmentation and selection can be
      elegantly achieved if structural connectivity interacts with neuronal
      synchronization. I propose that this process is at least one of the fundamental
      functions of gamma-band synchronization, which then subserves numerous higher
      cognitive functions.

PMID- 19400725
TI  - Neurocognitive mechanisms in depression: implications for treatment.
AB  - Mood disorders collectively account for a substantial proportion of disease
      burden across the globe and have a devastating impact on quality of life and
      occupational function. Here we evaluate recent progress in understanding the
      neurocognitive mechanisms involved in the manifestation of mood disorders. We
      focus on four domains of cognitive function that are altered in patients with
      depression: executive control, memory, affective processing, and feedback
      sensitivity. These alterations implicate a distributed neural circuit composed of
      multiple sectors of the prefrontal cortex in interaction with subcortical regions
      (striatum, thalamus) and temporal lobe structures (amygdala, hippocampus).
      Affective processing and feedback sensitivity are highly sensitive to
      serotonergic manipulation and are targeted by antidepressant treatments. By
      drawing together cognitive, neuroanatomical, and pharmacological tiers of
      research, we identify treatment targets and directions for future investigation
      to identify people at risk, minimize relapse, and maximize long-term beneficial
      outcomes for those suffering from depression.

PMID- 19400724
TI  - Neuropathic pain: a maladaptive response of the nervous system to damage.
AB  - Neuropathic pain is triggered by lesions to the somatosensory nervous system that
      alter its structure and function so that pain occurs spontaneously and responses
      to noxious and innocuous stimuli are pathologically amplified. The pain is an
      expression of maladaptive plasticity within the nociceptive system, a series of
      changes that constitute a neural disease state. Multiple alterations distributed
      widely across the nervous system contribute to complex pain phenotypes. These
      alterations include ectopic generation of action potentials, facilitation and
      disinhibition of synaptic transmission, loss of synaptic connectivity and
      formation of new synaptic circuits, and neuroimmune interactions. Although neural
      lesions are necessary, they are not sufficient to generate neuropathic pain;
      genetic polymorphisms, gender, and age all influence the risk of developing
      persistent pain. Treatment needs to move from merely suppressing symptoms to a
      disease-modifying strategy aimed at both preventing maladaptive plasticity and
      reducing intrinsic risk.

PMID- 19400727
TI  - A renaissance of elicitors: perception of microbe-associated molecular patterns
      and danger signals by pattern-recognition receptors.
AB  - Microbe-associated molecular patterns (MAMPs) are molecular signatures typical of
      whole classes of microbes, and their recognition plays a key role in innate
      immunity. Endogenous elicitors are similarly recognized as damage-associated
      molecular patterns (DAMPs). This review focuses on the diversity of MAMPs/DAMPs
      and on progress to identify the corresponding pattern recognition receptors
      (PRRs) in plants. The two best-characterized MAMP/PRR pairs, flagellin/FLS2 and
      EF-Tu/EFR, are discussed in detail and put into a phylogenetic perspective. Both
      FLS2 and EFR are leucine-rich repeat receptor kinases (LRR-RKs). Upon treatment
      with flagellin, FLS2 forms a heteromeric complex with BAK1, an LRR-RK that also
      acts as coreceptor for the brassinolide receptor BRI1. The importance of MAMP/PRR
      signaling for plant immunity is highlighted by the finding that plant pathogens
      use effectors to inhibit PRR complexes or downstream signaling events. Current
      evidence indicates that MAMPs, DAMPs, and effectors are all perceived as danger
      signals and induce a stereotypic defense response.

PMID- 19400728
TI  - Signal transduction in responses to UV-B radiation.
AB  - UV-B radiation is a key environmental signal that initiates diverse responses in
      plants that affect metabolism, development, and viability. Many effects of UV-B
      involve the differential regulation of gene expression. The response to UV-B
      depends on the nature of the UV-B treatment, the extent of adaptation and
      acclimation to UV-B, and interaction with other environmental factors. Responses
      to UV-B are mediated by both nonspecific signaling pathways, involving DNA
      damage, reactive oxygen species, and wound/defense signaling molecules, and UV-B
      specific pathways that mediate photomorphogenic responses to low levels of UV-B.
      Importantly, photomorphogenic signaling stimulates the expression of genes
      involved in UV-protection and hence promotes plant survival in UV-B.
      Photomorphogenic UV-B signaling is mediated by the UV-B-specific component UV
      RESISTANCE LOCUS8 (UVR8). Both UVR8 and CONSTITUTIVE PHOTOMORPHOGENESIS1 (COP1)
      are required for UV-B-induced expression of the ELONGATED HYPOCOTYL5 (HY5)
      transcription factor, which plays a central role in the regulation of genes
      involved in photomorphogenic UV-B responses.

PMID- 19400729
TI  - Genetically engineered plants and foods: a scientist's analysis of the issues
      (part II).
AB  - Genetic engineering provides a means to introduce genes into plants via
      mechanisms that are different in some respects from classical breeding. A number
      of commercialized, genetically engineered (GE) varieties, most notably canola,
      cotton, maize and soybean, were created using this technology, and at present the
      traits introduced are herbicide and/or pest tolerance. In 2007 these GE crops
      were planted in developed and developing countries on more than 280 million acres
      (113 million hectares) worldwide, representing nearly 10% of rainfed cropland.
      Although the United States leads the world in acres planted with GE crops, the
      majority of this planting is on large acreage farms. In developing countries,
      adopters are mostly small and resource-poor farmers. For farmers and many
      consumers worldwide, planting and eating GE crops and products made from them are
      acceptable and even welcomed; for others GE crops raise food and environmental
      safety questions, as well as economic and social issues. In Part I of this
      review, some general and food issues related to GE crops and foods were
      discussed. In Part II, issues related to certain environmental and socioeconomic
      aspects of GE crops and foods are addressed, with responses linked to the
      scientific literature.

PMID- 19400730
TI  - Technique for ureteral stent placement during robot-assisted radical
      prostatectomy: safety measure during vesicourethral anastomosis when ureteral
      orifices are too close for comfort.

PMID- 19400731
TI  - The effect of lunarlike satellites on the orbital infrared light curves of Earth
      analog planets.
AB  - We have investigated the influence of lunarlike satellites on the infrared
      orbital light curves of Earth-analog extrasolar planets. Such light curves will
      be obtained by NASA's Terrestrial Planet Finder (TPF) and ESA's Darwin missions
      as a consequence of repeat observations to confirm the companion status of a
      putative planet and determine its orbit. We used an energy balance model to
      calculate disk-averaged infrared (bolometric) fluxes from planet-satellite
      systems over a full orbital period (one year). The satellites are assumed to lack
      an atmosphere, have a low thermal inertia like that of the Moon, and span a range
      of plausible radii. The planets are assumed to have thermal and orbital
      properties that mimic those of Earth, while their obliquities and orbital
      longitudes of inferior conjunction remain free parameters. Even if the gross
      thermal properties of the planet can be independently constrained (e.g., via
      spectroscopy or visible-wavelength detection of specular glint from a surface
      ocean), only the largest (approximately Mars-sized) lunarlike satellites can be
      detected by light curve data from a TPF-like instrument (i.e., one that achieves
      a photometric signal-to-noise ratio of 10 to 20 at infrared wavelengths).
      Nondetection of a lunarlike satellite can obfuscate the interpretation of a given
      system's infrared light curve so that it may resemble a single planet with high
      obliquity, different orbital longitude of vernal equinox relative to inferior
      conjunction, and in some cases drastically different thermal characteristics. If
      the thermal properties of the planet are not independently established, then the
      presence of a lunarlike satellite cannot be inferred from infrared data, which
      would thus demonstrate that photometric light curves alone can only be used for
      preliminary study, and the addition of spectroscopic data will be necessary.

PMID- 19400726
TI  - Establishment of axon-dendrite polarity in developing neurons.
AB  - Neurons are among the most highly polarized cell types in the body, and the
      polarization of axon and dendrites underlies the ability of neurons to integrate
      and transmit information in the brain. Significant progress has been made in the
      identification of the cellular and molecular mechanisms underlying the
      establishment of neuronal polarity using primarily in vitro approaches such as
      dissociated culture of rodent hippocampal and cortical neurons. This model has
      led to the predominant view suggesting that neuronal polarization is specified
      largely by stochastic, asymmetric activation of intracellular signaling pathways.
      Recent evidence shows that extracellular cues can play an instructive role during
      neuronal polarization in vitro and in vivo. In this review, we synthesize the
      recent data supporting an integrative model whereby extracellular cues
      orchestrate the intracellular signaling underlying the initial break of neuronal
      symmetry leading to axon-dendrite polarization.

PMID- 19400732
TI  - Key scientific questions and key investigations from the first international
      conference on Martian phyllosilicates.
AB  - Minerals and their occurrences can tell us about the chemistry, pressure, and
      temperatures of past environments on Mars and thus allow inferences about the
      potential for habitability. Thanks to recent space exploration, a new vision is
      emerging wherein Mars hosted environmental conditions of potential
      astrobiological relevance. This epoch is identified by the presence of
      phyllosilicate-bearing deposits, which are generally contained in very ancient
      basement rocks. In October 2008, over 100 planetary scientists representing 11
      countries met in Paris to assess and discuss the relevance of martian
      phyllosilicates. The conference was structured to promote the discussion and
      debate of key scientific questions and key essential investigations. The purpose
      of this report is to document the current state of knowledge related to martian
      phyllosilicates and to ascertain which questions remain to be addressed: What are
      the basic characteristics of the phyllosilicate minerals on Mars? What are the
      genetic mechanisms by which phyllosilicate minerals have formed on Mars? What is
      the relationship between the phyllosilicate minerals observed in martian
      meteorites and those detected from orbit? What are the implications of
      phyllosilicate-bearing rocks for the development of prebiotic chemistry and the
      preservation of biosignatures? The most promising investigations to address these
      questions are presented.

PMID- 19400733
TI  - Isotopic composition of methane and inferred methanogenic substrates along a
      salinity gradient in a hypersaline microbial mat system.
AB  - The importance of hypersaline environments over geological time, the discovery of
      similar habitats on Mars, and the importance of methane as a biosignature gas
      combine to compel an understanding of the factors important in controlling
      methane released from hypersaline microbial mat environments. To further this
      understanding, changes in stable carbon isotopes of methane and possible
      methanogenic substrates in microbial mat communities were investigated as a
      function of salinity here on Earth. Microbial mats were sampled from four
      different field sites located within salterns in Baja California Sur, Mexico.
      Salinities ranged from 50 to 106 parts per thousand (ppt). Pore water and
      microbial mat samples were analyzed for the carbon isotopic composition of
      dissolved methane, dissolved inorganic carbon (DIC), and mat material
      (particulate organic carbon or POC). The POC delta(13)C values ranged from -6.7
      to -13.5 per thousand, and DIC delta(13)C values ranged from -1.4 to -9.6 per
      thousand. These values were similar to previously reported values. The delta(13)C
      values of methane ranged from -49.6 to -74.1 per thousand; the methane most
      enriched in (13)C was obtained from the highest salinity area. The apparent
      fractionation factors between methane and DIC, and between methane and POC,
      within the mats were also determined and were found to change with salinity. The
      apparent fractionation factors ranged from 1.042 to 1.077 when calculated using
      DIC and from 1.038 to 1.068 when calculated using POC. The highest-salinity area
      showed the least fractionation, the moderate-salinity area showed the highest
      fractionation, and the lower-salinity sites showed fractionations that were
      intermediate. These differences in fractionation are most likely due to changes
      in the dominant methanogenic pathways and substrates used at the different sites
      because of salinity differences.

PMID- 19400734
TI  - Analysis of human immunodeficiency virus type 1 nef gene sequences among inmates
      from prisons in China.
AB  - To provide the hard-won information on HIV-1 polymorphism from inmates in prison
      and to study the genetic variation of HIV-1 strains, we analyzed the
      characterization of the nucleotide and corresponding protein sequences of
      naturally occurring nef sequences derived from 16 HIV-1-positive inmates from
      prisons in China. Nested PCR and DNA sequencing were used to determine nef
      sequences in peripheral blood mononuclear cells. Phylogenetic analysis revealed a
      distribution of the viral sequences among subtype B, CRF_BC, and CRF_AE, with
      subtype B accounting for more than half of the genotypes. When compared with the
      consensus sequence, a certain amino acid sequence variability was observed.
      However, most of the described nef functional motifs were relatively well
      conserved in the majority of the sequences analyzed. Our results indicate that
      HIV-1 strains found in our study subjects may have a common origin and the
      description of motifs will produce important information for further studies of
      nef function.

PMID- 19400735
TI  - Human immunodeficiency virus type 1 gp 41 mutations in proviral DNA among
      antiretroviral treatment-naive individuals from India.
AB  - The HIV-1 gp41 has been identified as an important target for the immune
      response, for the development of antiviral and vaccine strategies, and for
      epidemiologic studies. This study describes the HIV-1 env gp41 region mutations,
      associated with enfuvirtide (ENF) resistance, in proviral DNA from PBMCs in
      antiretroviral treatment-naive individuals from Pune, India. Twenty-one
      antiretroviral drug-naive chronically HIV-1-infected individuals were enrolled.
      The study sequences belonged to subtype C (n = 17), subtype A1 (n = 2), and
      CRF_AE (n = 2). In subtype B-infected individuals, the various HR1 region
      substitutions in env gp41 that have been associated with ENF resistance include
      A30V, L33S/T/V, L34M, G36D/E/S/V, I37T/K/V, V38A/M/E/G, Q39R, Q40H, N42T/D,
      N43D/K/S, L44M, L45M, R46M, L54M, and Q56K/R as well as N126K and S138A in the
      HR2 region. The study sequences did not reveal any ENF resistance-associated
      mutations at env gp41 amino acid positions: 36 to 45. The presence of L54M and
      Q56K in combination is associated with 5-fold reduced sensitivity to inhibition
      by ENF. The mutation L54M was seen in seven subtype C and two CRF_AE study
      sequences. Q56K was observed in a subtype A1 sequence. All the study sequences
      harbored N42S, a natural polymorphism associated with increased susceptibility to
      ENF. Of the mutations V38A and N140I, known to provide immunologic gain, the
      latter was observed in four subtype C sequences. This is the first study from
      India highlighting the presence of certain mutations in Indian subtype C env
      gp41, which may play a role in the evolution of subtype-specific variations in
      the resistance to ENF and associated immune response.

PMID- 19400736
TI  - Structural basis of drug resistance by genetic variants of HIV type 1 clade c
      protease from India.
AB  - Using computer modeling of three-dimensional structures and structural
      information available on the crystal structures of HIV-1 protease, we
      investigated the structural effects of mutations, in treatment-naive and
      treatment-exposed individuals from India and postulated mechanisms of resistance
      in clade C variants. A large number of models (14) have been generated by
      computational mutation of the available crystal structures of drug bound
      proteases. Localized energy minimization was carried out in and around the sites
      of mutation in order to optimize the geometry of interactions present. Most of
      the mutations result in structural differences at the flap that favors the
      semiopen state of the enzyme. Some of the mutations were also found to confer
      resistance by affecting the geometry of the active site. The E35D mutation
      affects the flap structure in clade B strains and E35N and E35K mutation, seen in
      our modeled strains, have a more profound effect. Common polymorphisms at
      positions 36 and 63 in clade C also affected flap structure. Apart from a few
      other residues Gln-58, Asn-83, Asn-88, and Gln-92 and their interactions are
      important for the transition from the closed to the open state. Development of
      protease inhibitors by structure-based design requires investigation of
      mechanisms operative for clade C to improve the efficacy of therapy.

PMID- 19400742
TI  - Pathogenesis and management of the dyslipidemia of the metabolic syndrome.
AB  - The metabolic syndrome is a multiplex risk factor for atherosclerotic
      cardiovascular disease. The core components of the dyslipidemia of the metabolic
      syndrome, which most likely initiate atherosclerosis, are the "lipid triad" of
      high plasma triglycerides, low levels of high-density lipoprotein cholesterol
      (HDL-C), and a preponderance of small, dense low-density lipoprotein (LDL)
      particles. Postprandial lipemia is also recognized as an important component.
      Dysregulation of fat metabolism in the liver with overproduction of very-low
      density lipoprotein 1 (VLDL1) particles is considered the hallmark of the
      dyslipidemia of the metabolic syndrome. The cornerstone of therapy is therapeutic
      lifestyle change. If this does not correct the dyslipidemia, drug therapy may be
      required. LDL-C lowering with statins is the first-line treatment; however, there
      is ongoing debate as to whether further aggressive LDL-lowering therapy with
      higher-dose statins as opposed to comprehensive lipid management is the optimal
      therapy to reduce cardiovascular risk in subjects with the metabolic syndrome.
      Combination of a statin with a fibrate and/or nicotinic acid can improve all
      components of the dyslipidemia. However, there are, as yet, no large
      cardiovascular outcome studies that show a reduction in cardiovascular morbidity
      or mortality using combination therapy. The current LDL-C goal in high-risk
      patients with the metabolic syndrome is below 100 mg/dL, with a non-HDL goal of
      below 130 mg/dL. However, in very high-risk patients, such as those with
      established cardiovascular disease, an LDL-C goal of below 70 mg/dL is
      recommended.

PMID- 19400741
TI  - Nogo-66 regulates nanog expression through stat3 pathway in murine embryonic stem
      cells.
AB  - Homeodomain transcription factor Nanog plays a critical role in maintaining
      murine embryonic stem (ES) cells pluripotency. However, its expression regulation
      largely remains unknown. In this study we show that Nogo receptor (NgR)
      participates in the regulation of Nanog expression via Stat3 pathway. Activation
      of NgR results in the phosphorylation of Stat3 and increases expression levels of
      Nanog mRNA and protein, which inhibits differentiation of embryoid bodies. This
      up-regulation of Nanog can be abolished by NgR inhibitor PI-PLC and NEP1-40, or
      phospho-Stat3 inhibitor AG490 and rapamycin. Immunofluorescence assay
      demonstrates that NgR and its ligand Nogo-A/B exist on mouse blastocysts and
      cultured ES cells, suggesting NgR might play a role in early embryo development.

PMID- 19400743
TI  - Differentiation of porcine inner cell mass cells into proliferating neural cells.
AB  - Here we report the culture and differentiation of porcine neural cells derived
      from the inner cell masses (ICMs) of blastocyst-stage embryos. Manually dissected
      ICMs were cultured on feeder layers of inactivated mouse embryonic fibroblasts
      (MEFs). Neural rosette-like structures were selected and passaged mechanically.
      These structures were transient and disappeared after six passages. After
      transfer to Matrigel-coated dishes, the cells proliferated for approximately 2
      months. Expression of neural progenitor cell (NPC)-specific genes NESTIN, SOX1,
      SOX2, and MUSASHI as detected by RT-PCR suggests that the cell culture contained
      neural progenitor-like cells. To further confirm the culture of neural progenitor
      like cells, we analyzed their differentiation potential in vitro. The porcine
      neural cells were able to differentiate into glial fibrillary acidic protein
      (GFAP)-positive astrocytes and O4-positive oligodendrocytes, identified by
      quantitative RT-PCR and immunofluorescence. Differentiated cells expressed
      microtubule-associated protein 2 (MAP2) RNA but were unable to differentiate into
      neurons. It is concluded that porcine blastocysts have the ability to provide an
      expandable source of neural cells that can develop into glial subtypes.

PMID- 19400744
TI  - Rationale for revised penicillin susceptibility breakpoints versus Streptococcus
      pneumoniae: coping with antimicrobial susceptibility in an era of resistance.
AB  - In January 2008, the Clinical and Laboratory Standards Institute published
      revised susceptibility breakpoints for penicillin and Streptococcus pneumoniae,
      and shortly thereafter, the United States Food and Drug Administration similarly
      revised its breakpoints via changes in the package insert for penicillin. The
      revised susceptibility breakpoint is < or =2 microg/mL for nonmeningeal
      infections treated with parenteral penicillin at a dosage of 12 million units-24
      million units per day. The susceptibility breakpoint of < or =0.06 microg/mL
      remains unchanged for pneumococcal meningitis treated with parenteral penicillin
      at a dosage of > or =18 million units per day. Herein, we review the scientific
      basis for the revisions to the breakpoints, which were supported by
      microbiologic, pharmacokinetic and/or pharmacodynamic, and clinical data.
      Clinicians, once again, should feel comfortable prescribing penicillin for
      pneumococcal pneumonia and other pneumococcal infections outside the central
      nervous system.

PMID- 19400745
TI  - Recurrent Burkholderia infection in patients with chronic granulomatous disease:
      11-year experience at a large referral center.
AB  - The epidemiology of Burkholderia infection in persons with chronic granulomatous
      disease is poorly understood. We used species-specific polymerase chain reaction
      based assays and genotyping analyses to identify 32 strains representing 9
      Burkholderia species among 50 isolates recovered from 18 patients with chronic
      granulomatous disease. We found that recurrent pulmonary infection with distinct
      Burkholderia strains is common in chronic granulomatous disease.

PMID- 19400746
TI  - An outbreak of postoperative gram-negative bacterial endophthalmitis associated
      with contaminated trypan blue ophthalmic solution.
AB  - We report 6 cases of postsurgical endophthalmitis due to gram-negative bacteria
      associated with contaminated trypan blue dye from a compounding pharmacy.
      Unopened trypan blue syringes yielded Pseudomonas aeruginosa and Burkholderia
      cepacia complex on culture, with pulsed-field gel electrophoresis patterns
      indistinguishable from patient isolates. Contamination of compounded medications
      should be considered when investigating outbreaks of postoperative
      endophthalmitis.

PMID- 19400747
TI  - Predictors of kidney tubular dysfunction in HIV-infected patients treated with
      tenofovir: a pharmacogenetic study.
AB  - BACKGROUND: Tenofovir is one of the most widely used antiretroviral drugs.
      Tenofovir undergoes renal clearance by a combination of glomerular filtration and
      active tubular secretion. Although rare, the mechanism by which tenofovir causes
      renal damage is not well characterized. We have explored the association between
      kidney tubular dysfunction (KTD) and polymorphisms in genes encoding drug
      transporters. METHODS: All consecutive, human immunodeficiency virus (HIV)
      infected patients receiving tenofovir-containing antiretroviral regimens who were
      seen at a single institution during the first trimester of 2008 were enrolled in
      the study. KTD was defined by the presence of at least 2 of the following
      abnormalities: nondiabetic glucosuria, urine phosphate wasting,
      hyperaminoaciduria, beta2-microglobulinuria, and increased fractional excretion
      of uric acid. Twelve single-nucleotide polymorphisms in the ABCC2, ABCC4,
      SCL22A6, SLC22A11, and ABCB1 genes were analyzed using TaqMan 5'-nuclease assays.
      RESULTS: A total of 115 HIV-infected patients were examined, of whom 19 (16.5%)
      had KTD. The percentage of patients with KTD was higher among those with genotype
      CC at position -24 of ABCC2 than among those with genotypes CT and TT (24% [16 of
      68 patients] vs. 6% [3 of 47 patients]; P = .020). In a multivariate analysis,
      older age (odds ratio [OR], 1.1; 95% confidence interval [CI], 1.0-1.2; P =
      .024), lower body weight (OR, 0.9; 95% CI, 0.8-0.9; P = .048), and genotype CC at
      ABCC2 position -24 (OR, 5; 95% CI, 1.2-21; P = .027) were independently
      associated with KTD. CONCLUSIONS: Approximately 17% of HIV-infected patients
      treated with tenofovir had KTD. Homozygosity for the C allele at position -24 of
      the ABCC2 gene was strongly associated with KTD in this population. This
      polymorphism may help to identify patients at greater risk for developing
      tenofovir-associated tubulopathy, and close monitoring of renal function is
      warranted for these patients.

PMID- 19400748
TI  - Transmission of Trypanosoma cruzi by heart transplantation.
AB  - BACKGROUND: Trypanosoma cruzi infection (i.e., Chagas disease) is an unusual
      complication that can occur after solid-organ transplantation and that can result
      in severe illness or death. In 2006, there were 2 heart transplant recipients in
      Los Angeles, California, reported to have acute trypanosomiasis during the same
      month. We conducted an investigation to determine the source of these infections.
      METHODS: We reviewed the medical, organ procurement, and donor transfusion and
      transplantation records of these 2 heart transplant recipients. The 2 heart
      transplant recipients were interviewed regarding any kind of natural exposure and
      were screened for parasites by obtaining blood and other tissue samples for buffy
      coat, culture, and polymerase chain reaction. Serum samples from the heart
      transplant recipients, organ donors, and blood donors were tested for T. cruzi
      antibodies by use of immunofluorescence assay and radioimmunoprecipitation assay.
      Tissue samples from the organ donors were examined by use of polymerase chain
      reaction and immunohistochemical staining. Other recipients of organs from the
      same donors were monitored for T. cruzi infection by use of polymerase chain
      reaction and immunofluorescence assay. RESULTS: Both heart transplant recipients
      had no apparent risk factors for preexisting T. cruzi infection. Both were
      seronegative but tested positive for the parasite, indicating recent infection.
      Both recipients died despite medical treatment. The organ donors tested positive
      for T. cruzi antibodies by use of radioimmunoprecipitation assay; the blood
      donors were seronegative. Six other patients had received a liver or kidney from
      these organ donors. None showed evidence of T. cruzi infection. CONCLUSIONS: To
      our knowledge, this is the first report of T. cruzi transmission associated with
      heart transplantation. Clinicians and public health authorities should be aware
      that manifestations of Chagas disease can occur after transplantation, requiring
      rapid evaluation, diagnosis, and treatment.

PMID- 19400749
TI  - Lack of evidence for frequent heterosexual transmission of human herpesvirus 8 in
      Zimbabwe.
AB  - BACKGROUND: There is conflicting evidence about the contribution of heterosexual
      transmission to the spread of human herpesvirus 8 (HHV-8) in southern Africa.
      This study evaluated the hypothesis that HHV-8 infection is associated with risk
      factors for human immunodeficiency virus type 1 (HIV-1) and other sexually
      transmitted infections among Zimbabwean men. METHODS: HHV-8 seroprevalence was
      determined for 2750 participants in the Zimbabwe AIDS Prevention Project cohort
      of male factory workers in Harare, Zimbabwe. Potential associations of HHV-8
      antibody detection with risk factors for HIV-1 infection were examined by
      univariate analysis. Variables with P < .1 in the univariate analysis were
      included in a multivariate logistic regression model. HHV-8 seroprevalence was
      also determined among 297 heterosexual couples. RESULTS: Prevalence of HHV-8, HIV
      1, and HHV-8 and HIV-1 coinfection was 28.5% (95% confidence interval [CI], 26.8%
      30.2%), 19.5% (95% CI, 18.0%-20.9%), and 6.5% (95% CI, 5.6%-7.5%), respectively.
      Detection of HHV-8 antibodies was independently associated with older age and HIV
      1 infection but not with number of recent sex partners, marital status,
      education, condom use, prior sexually transmitted infections, payment for sex,
      chronic hepatitis B infection, or incident HIV-1 infection. HHV-8 seroprevalence
      was 31.7% (95% CI, 26.3-37.0) among wives in the couples tested, but HHV-8
      infection of wives was not associated with HHV-8 infection of husbands (odds
      ratio, 1.08; 95% CI, 0.62-1.88; P = .8). CONCLUSIONS: HHV-8 and HIV-1 infection
      did not have common sexual risk factors among urban Zimbabwean men. Sexual
      transmission does not explain the high prevalence of HHV-8 in this population.

PMID- 19400750
TI  - Dietary protein, weight loss, and weight maintenance.
AB  - The role of dietary protein in weight loss and weight maintenance encompasses
      influences on crucial targets for body weight regulation, namely satiety,
      thermogenesis, energy efficiency, and body composition. Protein-induced satiety
      may be mainly due to oxidation of amino acids fed in excess, especially in diets
      with "incomplete" proteins. Protein-induced energy expenditure may be due to
      protein and urea synthesis and to gluconeogenesis; "complete" proteins having all
      essential amino acids show larger increases in energy expenditure than do lower
      quality proteins. With respect to adverse effects, no protein-induced effects are
      observed on net bone balance or on calcium balance in young adults and elderly
      persons. Dietary protein even increases bone mineral mass and reduces incidence
      of osteoporotic fracture. During weight loss, nitrogen intake positively affects
      calcium balance and consequent preservation of bone mineral content. Sulphur
      containing amino acids cause a blood pressure-raising effect by loss of nephron
      mass. Subjects with obesity, metabolic syndrome, and type 2 diabetes are
      particularly susceptible groups. This review provides an overview of how
      sustaining absolute protein intake affects metabolic targets for weight loss and
      weight maintenance during negative energy balance, i.e., sustaining satiety and
      energy expenditure and sparing fat-free mass, resulting in energy inefficiency.
      However, the long-term relationship between net protein synthesis and sparing fat
      free mass remains to be elucidated.

PMID- 19400752
TI  - Mammalian zinc transporters: nutritional and physiologic regulation.
AB  - Research advances defining how zinc is transported into and out of cells and
      organelles have increased exponentially within the past five years. Research has
      progressed through application of molecular techniques including genomic
      analysis, cell transfection, RNA interference, kinetic analysis of ion transport,
      and application of cell and animal models including knockout mice. The knowledge
      base has increased for most of 10 members of the ZnT family and 14 members of the
      Zrt-, Irt-like protein (ZIP) family. Relative to the handling of dietary zinc is
      the involvement of ZnT1, ZIP4, and ZIP5 in intestinal zinc transport, involvement
      of ZIP10 and ZnT1 in renal zinc reabsorption, and the roles of ZIP5, ZnT2, and
      ZnT1 in pancreatic release of endogenous zinc. These events are major factors in
      regulation of zinc homeostasis. Other salient findings are the involvement of
      ZnT2 in lactation, ZIP14 in the hypozincemia of inflammation, ZIP6, ZIP7, and
      ZIP10 in metastatic breast cancer, and ZnT8 in insulin processing and as an
      autoantigen in diabetes.

PMID- 19400753
TI  - Nutrient biofortification of food crops.
AB  - Plant-based foods offer an array of nutrients that are essential for human
      nutrition and promote good health. However, the major staple crops of the world
      are often deficient in some of these nutrients. Traditional agricultural
      approaches can marginally enhance the nutritional value of some foods, but the
      advances in molecular biology are rapidly being exploited to engineer crops with
      enhanced key nutrients. Nutritional targets include elevated mineral content,
      improved fatty acid composition, increased amino acid levels, and heightened
      antioxidant levels. Unfortunately, in many cases the benefits of these
      "biofortified" crops to human nutrition have not been demonstrated.

PMID- 19400754
TI  - Treatment of cryptosporidiosis.

PMID- 19400755
TI  - Promising anti-HIV gel in large-scale study in women.

PMID- 19400756
TI  - No let up in the search for novel antibiotics.

PMID- 19400751
TI  - Management of the metabolic syndrome and type 2 diabetes through lifestyle
      modification.
AB  - Sustainable lifestyle modifications in diet and physical activity are the
      initial, and often the primary, component in the management of diabetes and the
      metabolic syndrome. An energy-prudent diet, coupled with moderate levels of
      physical activity, favorably affects several parameters of the metabolic syndrome
      and delays the onset of diabetic complications. Weight loss, albeit not an
      absolute prerequisite for improvement, is a major determinant and maximizes
      effectiveness. Adopting a healthy lifestyle pattern requires a series of long
      term behavioral changes, but evidence to date indicates low long-term adherence
      to diet and physical activity recommendations. This calls for greater research
      and public health efforts focusing on strategies to facilitate behavior
      modification.

PMID- 19400757
TI  - Selective decontamination of the digestive tract and oropharynx: new findings for
      an old approach still under discussion.

PMID- 19400758
TI  - Aciclovir, herpes viruses and HIV: a never-ending story.

PMID- 19400759
TI  - Ambiguous role of pfcrt K76 in Plasmodium falciparum: a marker of resistance or
      increased susceptibility.

PMID- 19400761
TI  - Linezolid for patients with neutropenia: are bacteriostatic agents appropriate?
AB  - A long-held doctrine is that bactericidal antibiotics are required for infections
      in neutropenic patients. We evaluated the available published evidence regarding
      the role of linezolid, a bacteriostatic antibiotic, in neutropenic patients with
      Gram-positive infection. We retrieved two prospective comparative studies (one of
      them a double-blind, randomized, controlled trial), a prospective cohort study,
      two retrospective studies and eight case reports that focused on the use of
      linezolid for Gram-positive bacterial infections in neutropenic patients.
      Linezolid was administered to 438 neutropenic patients, mainly on a compassionate
      use basis, as other antibiotics failed to cure the infection or were associated
      with significant adverse events. The clinical cure rate ranged between 57 and
      87.3% in the intention-to-treat population of the prospective studies. In total,
      56 out of 438 (12.7%) neutropenic patients that received linezolid died during
      therapy. In the only randomized controlled trial that compared linezolid with
      vancomycin in the treatment of Gram-positive infections in neutropenic patients,
      mortality was 5.6 versus 7.6%, respectively (p = 0.4). In conclusion, the
      available evidence suggests that linezolid may be successful in a significant
      proportion of neutropenic patients with infection, despite the fact that it is a
      bacteriostatic agent. Such data seem to justify further studies regarding the
      role of linezolid in this patient population.

PMID- 19400762
TI  - Fibroblastic reticular cells and their role in viral hemorrhagic fevers.
AB  - Viral hemorrhagic fevers (VHFs) caused by Ebola, Marburg and Lassa viruses often
      manifest as multiple organ dysfunction and hemorrhagic shock with high mortality.
      These viruses target numerous cell types, including monocytes and dendritic
      cells, which are primary early targets that mediate critical pathogenetic
      processes. This review focuses on fibroblastic reticular cells (FRCs), another
      prevalent infected cell type that is known as a key regulator of circulatory and
      immune functions. Viral infection of FRCs could have debilitating effects in
      secondary lymphoid organs and various other tissues. FRCs may also contribute to
      the spread of these deadly viruses throughout the body. Here, we review the
      salient features of these VHFs and the biology of FRCs, emphasizing the potential
      role of these cells in VHFs and the rapid deterioration of immune and
      hemovascular sytems that are characteristic of such acute infections.

PMID- 19400763
TI  - Management of community-acquired pneumonia in HIV-infected children.
AB  - Pneumonia is a major cause of childhood mortality and morbidity worldwide,
      particularly in low-income countries. Often, these are also the countries most
      affected by the HIV epidemic. Pneumonia is the leading cause of death in HIV
      infected children and a major cause of hospitalization and healthcare
      utilization. A broader spectrum of organisms, such as Pneumocystis jiroveci and
      Gram-negative bacteria, cause pneumonia in HIV-infected children compared with
      uninfected children. Etiologic organisms have higher rates of antimicrobial
      resistance in HIV-infected children. Polymicrobial disease is more common in HIV
      infected children and associated with an exponential increase in mortality rate.
      HIV-infected children develop more severe pneumonia and have a worse outcome than
      HIV-uninfected children. HIV-exposed but HIV-negative children are also at higher
      risk of severe pneumonia and death compared with HIV-unexposed children. Although
      case-management guidelines for childhood pneumonia have led to an overall
      decrease in global childhood morbidity and mortality, HIV-infected children
      continue to have unacceptably high treatment failure and case fatality rates
      despite adherence to these guidelines. Standard guidelines require adaptation for
      use in high HIV-prevalence areas. Specific preventive interventions, including
      chemoprophylaxis for P. jiroveci pneumonia or for TB and early initiation of
      highly active antiretroviral therapy, may significantly reduce the burden of
      pneumonia in HIV-infected children.

PMID- 19400764
TI  - Antifungal drug resistance mechanisms.
AB  - Antifungal resistance is a prominent feature in the management of invasive
      mycoses, with important implications for morbidity and mortality. Microbiological
      resistance, the most common cause of refractory infection, is associated with a
      fungal pathogen for which an antifungal MIC is higher than average or within the
      range designated as the resistant breakpoint. Four major mechanisms of resistance
      to azoles have been described in Candida spp.: decreased intracellular drug
      concentration by activation of efflux systems or reduction of drug penetration,
      modification of the target site, upregulation of the target enzyme and
      development of bypass pathways. Conversely, echinocandins are a poor substrate
      for multidrug efflux transporters, and their mechanisms of resistance are
      associated with point mutations and/or overexpression of FKS1 and FKS2 genes.
      Acquired resistance to flucytosine results from defects in its metabolism through
      enzymatic mutations, whereas resistance to amphotericin B may be mediated by
      increased catalase activity or defects in ergosterol biosynthesis.

PMID- 19400765
TI  - Diagnosis and treatment of aspergillosis in children.
AB  - Invasive fungal infections cause significant morbidity and mortality in
      immunocompromised children. The prevalence of invasive aspergillosis (IA) is
      increasing as a reflection of the rising numbers of immunocompromised patients
      and the increasing use of aggressive immunosuppressive treatment regimes for
      hematologic malignancies and transplantation. IA is almost exclusively seen in
      severely immunocompromised or critically ill children, including those with the
      classic risk factors (particularly neutropenia, hematopoietic stem cell
      transplant or solid-organ transplantation, hematological malignancies, use of
      systemic immunosuppressive agents or cytotoxic therapies). Early treatment
      improves survival rates, but the diagnosis of aspergillosis remains difficult
      and, while IA has been relatively well-characterized in adults, far fewer studies
      have described optimal treatment for the pediatric population. This article
      reviews and compares the newer, less-invasive diagnostic techniques that are
      becoming available and focuses on the data specifically from pediatric trials
      regarding efficacy, safety and pharmacokinetics of the antifungals used for IA.

PMID- 19400766
TI  - Conquering 'snail fever': schistosomiasis and its control in China.
AB  - Schistosomiasis japonica is a serious parasitic disease and a major health risk
      for more than 60 million people living in the tropical and subtropical zones of
      south China. The disease is a zoonosis and its cause, the parasitic trematode
      Schistosoma japonicum, has a range of mammalian reservoirs, making control
      efforts difficult. Current control programs are heavily based on community
      chemotherapy with a single dose of the highly effective drug praziquantel.
      However, vaccines (for use in bovines and in humans) in combination with other
      control strategies are needed to eliminate the disease. In this review, we
      provide an overview of the transmission, clinical features, pathogenesis,
      diagnosis, treatment, genetics and susceptibility, epidemiology, and prospects
      for control of schistosomiasis japonica in China. The threat posed by the Three
      Gorges Dam may undermine control efforts because it will change the local ecology
      and associated schistosomiasis transmission risks over the next decade and
      beyond.

PMID- 19400768
TI  - Pseudomonas aeruginosa MurE amide ligase: enzyme kinetics and peptide inhibitor.
AB  - The enzyme kinetics of the amide ligase MurE, a cell wall biosynthesis enzyme,
      from Pseudomonas aeruginosa were determined using the synthesized nucleotide
      substrate UDP-MurNAc-Ala-Glu (uridine 5'-diphosphoryl N-acetylmuramoyl-L-alanyl-D
      glutamate). When coupled to a competitive bio-panning technique using a M13 phage
      display library encoding approximately 2.7 x 10(9) random peptide permutations
      and the specific substrates meso-A2pm (meso-diaminopimelic acid) and ATP, a
      peptide inhibitor of MurE was identified. The MurEp1 dodecamer selected and
      synthesized inhibited MurE ATPase activity with an IC(50) value of 500 microM.
      The inhibition was shown to be time-dependent and was reversed by the addition of
      meso-A2pm or UDP-MurNAc-Ala-Glu during the pre-incubation step. Kinetic analysis
      defined MurEp1 as a mixed inhibitor against both substrates with K(i) values of
      160 and 80 microM respectively. MurEp1 was found to interfere in meso-A2pm and
      UDP-MurNAc-Ala-Glu binding necessary for amide bond formation. Modelling of Ps.
      aeruginosa MurE and docking of MurEp1 on the Ps. aeruginosa MurE surface
      indicated that MurEp1 binds at the juxtaposition of both meso-A2pm- and UDP
      MurNAc-Ala-Glu-binding sites in the closed conformational state of the enzyme.
      Identification of the MurEp1 residues involved in MurE binding and inhibition
      will allow the development of a novel class of inhibitors having a novel mode of
      action against MurE.

PMID- 19400770
TI  - New insights into the protective effect of manganese against oxidative stress.
AB  - Manganese has emerged as an important trace element in bacterial physiology. The
      correlation between manganese accumulation and resistance to oxidative stress has
      led to the suggestion that, in addition to a role as a prosthetic group in
      superoxide dismutase, manganese could exert its antioxidant effect via non
      enzymatic redox reactions. The article by Anjem et al. in the current issue of
      Molecular Microbiology investigates the role of manganese ions in the defence
      against hydrogen peroxide in Escherichia coli. The results indicate that the
      redox activity of manganese is not linked to its protective effect. Instead, it
      is suggested that manganese replaces ferrous iron in enzymes that contain
      divalent cations at their active site. This enables the cell to avoid oxidative
      stress associated with iron release in the presence of hydrogen peroxide.

PMID- 19400769
TI  - Manganese import is a key element of the OxyR response to hydrogen peroxide in
      Escherichia coli.
AB  - Very little manganese is imported into Escherichia coli under routine growth
      conditions: the import system is weakly expressed, the manganese content is low,
      and a manganese-dependent enzyme is not correctly metallated. Mutants that lack
      MntH, the importer, grow at wild-type rates, indicating that manganese plays no
      critical role. However, MntH supports the growth of iron-deficient cells,
      suggesting that manganese can substitute for iron in activating at least some
      metalloenzymes. MntH is also strongly induced when cells are stressed by hydrogen
      peroxide. This adaptation is essential, as E. coli cannot tolerate peroxide
      stress if mntH is deleted. Other workers have observed that manganese improves
      the ability of a variety of microbes to tolerate oxidative stress, and the
      prevailing hypothesis is that manganese does so by chemically scavenging hydrogen
      peroxide and/or superoxide. We found that manganese does not protect peroxide
      stressed cells by scavenging peroxide. Instead, the beneficial effects of
      manganese correlate with its ability to metallate mononuclear enzymes. Because
      iron-loaded enzymes are vulnerable to the Fenton reaction, the substitution of
      manganese may prevent protein damage. Accordingly, during H2O2 stress, mutants
      that cannot import manganese and/or are unable to sequester iron suffer high
      rates of protein oxidation.

PMID- 19400771
TI  - CsiA is a bacterial cell wall synthesis inhibitor contributing to DNA
      translocation through the cell envelope.
AB  - Conjugation is a widely spread mechanism allowing bacteria to adapt and evolve by
      acquiring foreign DNA. The chromosome of Lactococcus lactis MG 1363 contains a 60
      kb conjugative element called the sex factor capable of high-frequency DNA
      transfer. Yet, little is known about the proteins involved in this process.
      Comparative genomics revealed a close relationship between the sex factor and
      elements found in Gram-positive pathogenic cocci. Among the conserved gene
      products, CsiA is a large protein that contains a highly conserved domain (HCD)
      and a C-terminal cysteine, histidine-dependent amidohydrolases/peptidases (CHAP)
      domain in its C-terminal moiety. Here, we show that CsiA is required for DNA
      transfer. Surprisingly, increased expression of CsiA affects cell viability and
      the cells become susceptible to lysis. Point mutagenesis of HCD reveals that this
      domain is responsible for the observed phenotypes. Growth studies and electron
      microscope observations suggest that CsiA is acting as a cell wall synthesis
      inhibitor. In vitro experiments reveal the capacity of CsiA to bind d-Ala-d-Ala
      analogues and to prevent the action of penicillin binding proteins. Our results
      strongly suggest that CsiA sequesters the peptidoglycan precursor and prevents
      the final stage of cell wall biosynthesis to enable the localized assembly of the
      DNA transfer machinery through the cell wall.

PMID- 19400772
TI  - Two small ncRNAs jointly govern virulence and transmission in Legionella
      pneumophila.
AB  - To transit from intra- to extracellular environments, Legionella pneumophila
      differentiates from a replicative/non-virulent to a transmissive/virulent form
      using the two-component system LetA/LetS and the global repressor protein CsrA.
      While investigating how both regulators act co-ordinately we characterized two
      ncRNAs, RsmY and RsmZ, that link the LetA/LetS and CsrA regulatory networks. We
      demonstrate that LetA directly regulates their expression and show that RsmY and
      RsmZ are functional in Escherichia coli and are able to bind CsrA in vitro.
      Single mutants have no (DeltarsmY) or a little (DeltarsmZ) impact on virulence,
      but the DeltarsmYZ strain shows a drastic defect in intracellular growth in
      Acanthamoeba castellanii and THP-1 monocyte-derived macrophages. Analysis of the
      transcriptional programmes of the DeltaletA, DeltaletS and DeltarsmYZ strains
      revealed that the switch to the transmissive phase is partially blocked. One
      major difference between the DeltaletA, DeltaletS and DeltarsmYZ strains was that
      the latter synthesizes flagella. Taken together, LetA activates transcription of
      RsmY and RsmZ, which sequester CsrA and abolish its post-transcriptional
      repressive activity. However, the RsmYZ-CsrA pathway appears not to be the main
      or only regulatory circuit governing flagella synthesis. We suggest that rather
      RpoS and LetA, by influencing LetE and probably cyclic-di-GMP levels, regulate
      motility in L. pneumophila.

PMID- 19400773
TI  - The pleiotropic regulator AdpA-L directly controls the pathway-specific activator
      of nikkomycin biosynthesis in Streptomyces ansochromogenes.
AB  - The nikkomycin-producing strain Streptomyces ansochromogenes has a homologue
      (adpA-L) of the key pleiotropic Streptomyces regulatory gene adpA. Gene
      disruption and genetic complementation revealed that adpA-L was required for both
      nikkomycin biosynthesis and morphological differentiation. Transcriptional
      analysis suggested that the transcription of sanG, the specific activator gene
      for nikkomycin biosynthesis, was dependent on AdpA-L. In gel-shift and DNase 1
      footprinting assays, the purified His(6)-tagged recombinant AdpA-L protein bound
      the upstream region of sanG at five sites, which are spread over more than one
      kilobase of DNA and most of which is inside the transcribed region. A consensus
      AdpA-L-binding sequence, 5'-TGGCNNVWHN-3' (V: C, A or G; W: A or T; H: A, T or C;
      N: any nucleotide) was found in these binding sites. Transcriptional analysis of
      sanG carrying mutated AdpA-L binding sites showed that transcription of sanG was
      eliminated when site I was mutated and its trascription was decreased when site V
      was mutated, whereas it was increased when the binding sites II, III or IV were
      mutated. Meanwhile, nikkomycin production of the mutated site III strain was
      enhanced comparing with the wild-type strain as control. This work highlights a
      new level of complexity in the regulation of nikkomycin biosynthesis.

PMID- 19400774
TI  - Hap2 regulates the pheromone response transcription factor prf1 in Ustilago
      maydis.
AB  - In Ustilago maydis the pheromone signal is transmitted via a mitogen-activated
      protein kinase (MAP kinase) module to the transcription factor Prf1. Prf1
      activates transcription of a and b mating type genes by binding to pheromone
      response elements (PREs) located in regulatory regions of these genes. Here we
      show that the CCAAT-box binding protein Hap2 from U. maydis regulates prf1
      expression. Hap2 was initially identified as a potential interaction partner of
      the MAP kinase Kpp6 in yeast two-hybrid screens and was subsequently also shown
      to interact with the MAPK Kpp2. Deletion of hap2 in haploid cells abolished
      mating, resulting from a defect in pheromone-induced gene expression. Crosses of
      haploid hap2 deletion strains were completely impaired in pathogenicity.
      Constitutive expression of prf1 complemented the pheromone response defect in
      Deltahap2 strains. Chromatin immunoprecipitation assays indicated that Hap2 binds
      directly to CCAAT motifs in the prf1 promoter. Point mutations in two putative
      MAPK phosphorylation sites in Hap2 attenuated the pheromone response. In a
      solopathogenic strain hap2 deletion affected filamentation and the mutants showed
      reduced pathogenicity symptoms. These data suggest that Hap2 is a novel regulator
      of prf1 with additional functions after cell fusion.

PMID- 19400775
TI  - Escherichia coli DnaA forms helical structures along the longitudinal cell axis
      distinct from MreB filaments.
AB  - DnaA initiates chromosomal replication in Escherichia coli at a well-regulated
      time in the cell cycle. To determine how the spatial distribution of DnaA is
      related to the location of chromosomal replication and other cell cycle events,
      the localization of DnaA in living cells was visualized by confocal fluorescence
      microscopy. The gfp gene was randomly inserted into a dnaA-bearing plasmid via in
      vitro transposition to create a library that included internally GFP-tagged DnaA
      proteins. The library was screened for the ability to rescue dnaA(ts) mutants,
      and a candidate gfp-dnaA was used to replace the dnaA gene of wild-type cells.
      The resulting cells produce close to physiological levels of GFP-DnaA from the
      endogenous promoter as their only source of DnaA and somewhat under-initiate
      replication with moderate asynchrony. Visualization of GFP-tagged DnaA in living
      cells revealed that DnaA adopts a helical pattern that spirals along the long
      axis of the cell, a pattern also seen in wild-type cells by immunofluorescence
      with affinity purified anti-DnaA antibody. Although the DnaA helices closely
      resemble the helices of the actin analogue MreB, co-visualization of GFP-tagged
      DnaA and RFP-tagged MreB demonstrates that DnaA and MreB adopt discrete helical
      structures along the length of the longitudinal cell axis.

PMID- 19400776
TI  - Evidence for a dual role of PBP1 in the cell division and cell separation of
      Staphylococcus aureus.
AB  - Penicillin-binding proteins (PBPs) catalyse the synthesis of cell wall
      peptidoglycan. PBP1 of Staphylococcus aureus is a high-molecular-weight
      monofunctional transpeptidase (TPase) and previous studies with a conditional
      mutant showed that this protein was essential for bacterial growth and survival:
      cells in which PBP1 was depleted stopped dividing but continued to enlarge in
      size, accompanied by rapid loss of viability. Also, cell walls produced under
      PBP1 depletion appeared to have normal composition. We describe here construction
      of a second PBP1 mutant in which the active site of the TPase domain was
      inactivated. Cells in which the wild-type PBP1 was replaced by the mutant protein
      were able to initiate and complete septa and undergo at least one or two cell
      divisions after which growth stopped accompanied by inhibition of cell
      separation, downregulation in the transcription of the autolytic system and
      production of cell walls with increased proportion of monomeric and dimeric
      muropeptides and decrease in oligomeric muropeptides. PBP1 seems to perform a
      dual role in the cell cycle of S. aureus: as a protein required for septation and
      also as a transpeptidase that generates a critical signal for cell separation at
      the end of cell division.

PMID- 19400777
TI  - Cooperativity between Plasmodium falciparum adhesive proteins for invasion into
      erythrocytes.
AB  - Plasmodium falciparum is the most virulent of the Plasmodium species infective to
      humans. Different P. falciparum strains vary in their dependence on erythrocyte
      receptors for invasion and their ability to switch in their utilization of
      different receptor repertoires. Members of the reticulocyte-binding protein-like
      (RBL) family of invasion ligands are postulated to play a central role in
      defining ligand-receptor interactions, known as invasion pathways. Here we report
      the targeted gene disruption of PfRh2b and PfRh2a in W2mef, a parasite strain
      that is heavily dependent on sialic-acid receptors for invasion, and show that
      the PfRh2b ligand is functional in this parasite background. Like the parental
      line, parasites lacking either PfRh2a or PfR2b can switch to a sialic acid
      independent invasion pathway. However, both of the switched lines exhibit a
      reduced efficiency for invasion into sialic acid-depleted cells, suggesting a
      role for both PfRh2b and PfRh2a in invasion via sialic acid-independent
      receptors. We also find a strong selective pressure for the reconstitution of
      PfRh2b expression at the expense of PfRh2a. Our results reveal the importance of
      genetic background in ligand-receptor usage by P. falciparum parasites, and
      suggest that the co-ordinate expression of PfRh2a, PfRh2b together mediate
      efficient sialic acid-independent erythrocyte invasion.

PMID- 19400778
TI  - Characterization of staphyloferrin A biosynthetic and transport mutants in
      Staphylococcus aureus.
AB  - Iron is critical for virtually all forms of life. The production of high-affinity
      iron chelators, siderophores, and the subsequent uptake of iron-siderophore
      complexes are a common strategy employed by microorganisms to acquire iron.
      Staphylococcus aureus produces siderophores but genetic information underlying
      their synthesis and transport is limited. Previous work implicated the sbn operon
      in siderophore synthesis and the sirABC operon in uptake. Here we characterize a
      second siderophore biosynthetic locus in S. aureus; the locus consists of four
      genes (in strain Newman these open reading frames are designated NWMN_2079-2082)
      which, together, are responsible for the synthesis and export of staphyloferrin
      A, a polycarboxylate siderophore. While deletion of the NWMN_2079-2082 locus did
      not affect iron-restricted growth of S. aureus, strains bearing combined sbn and
      NWMN_2079-2082 locus deletions produced no detectable siderophore and
      demonstrated severely attenuated iron-restricted growth. Adjacent to NWMN_2079
      2082 resides the htsABC operon, encoding an ABC transporter previously implicated
      in haem acquisition. We provide evidence here that HtsABC, along with the FhuC
      ATPase, is required for the uptake of staphyloferrin A. The crystal structure of
      apo-HtsA was determined and identified a large positively charged region in the
      substrate-binding pocket, in agreement with a role in binding of anionic
      staphyloferrin A.

PMID- 19400779
TI  - Biosynthesis of the red pigment bikaverin in Fusarium fujikuroi: genes, their
      function and regulation.
AB  - Fusarium secondary metabolites are structurally diverse, have a variety of
      activities and are generally poorly understood biosynthetically. The F. fujikuroi
      polyketide synthase gene bik1 was previously shown to be responsible for
      formation of the mycelial pigment bikaverin. Here we present the characterization
      of five genes adjacent to bik1 as encoding a putative FAD-dependent monooxygenase
      (bik2), an O-methyltransferase (bik3), an NmrA-like protein (bik4), a Zn(II)2Cys6
      transcription factor (bik5) and an MFS transporter (bik6). Deletion of each gene
      resulted in total loss or significant reduction of bikaverin synthesis.
      Expression studies revealed that all bik genes are repressed by high amounts of
      nitrogen in an AreA-independent manner and are subject to a time- and pH
      dependent regulation. Deletion of the pH regulatory gene pacC resulted in partial
      derepression while complementation with a dominant active allele resulted in
      repression of bik genes at acidic ambient pH. Transcription of all bik genes in
      strains lacking bik1, bik2 or bik3 was essentially eliminated, while
      transcription of some bik genes was detected in strains lacking bik4, bik5 or
      bik6. Thus, bikaverin synthesis is regulated by a complex regulatory network.
      Understanding how different factors influence the synthesis of this model
      secondary metabolite will aid understanding secondary metabolism in general.

PMID- 19400780
TI  - Ectopic production of VapCs from Enterobacteria inhibits translation and trans
      activates YoeB mRNA interferase.
AB  - Toxin-antitoxin loci have been identified in almost all free-living prokaryotes,
      often in high copy numbers. The biological function and molecular targets of the
      abundant vapBC loci are not yet known. Here we analyse the vapBC loci of
      Salmonella LT2 and Shigella plasmid pMYSH6000. Both loci encode putative PIN
      (PilT N-terminal) domain toxins, and antitoxins that may regulate vapBC
      transcription. We show that vapBC(LT2) and vapBC(pMYSH) are bona fide TA loci:
      (i) both VapCs inhibited cell growth very efficiently and were counteracted by
      the cognate VapBs; (ii) both VapCs inhibited translation; (iii) transcription of
      the vapBC loci was induced by amino acid starvation and chloramphenicol,
      consistent with the proposal that VapB is an unstable inhibitor of vapBC
      transcription; (iv) ectopic expression of both VapCs induced a bacteriostatic
      condition that could be reversed by the cognate antitoxins. Unexpectedly,
      induction of vapC in Escherichia coli resulted in mRNA cleavage at stop-codons.
      Surprisingly, these cleavages depended on the yefM yoeB locus, indicating cross
      activation between different toxins, that is, VapC activated YoeB mRNA
      interferase. Activation of YoeB depended on Lon, indicating that Lon degrades
      YefM antitoxin. Based on these results we present a model that explains
      activation of YoeB.

PMID- 19400781
TI  - Identification of genes involved in the assembly and attachment of a novel
      flagellin N-linked tetrasaccharide important for motility in the archaeon
      Methanococcus maripaludis.
AB  - Recently, the flagellin proteins of Methanococcus maripaludis were found to
      harbour an N-linked tetrasaccharide composed of N-acetylgalactosamine, di
      acetylated glucuronic acid, an acetylated and acetamidino-modified mannuronic
      acid linked to threonine, and a novel terminal sugar [(5S)-2-acetamido-2,4
      dideoxy-5-O-methyl-alpha-L-erythro-hexos-5-ulo-1,5-pyranose]. To identify genes
      involved in the assembly and attachment of this glycan, in-frame deletions were
      constructed in putative glycan assembly genes. Successful deletion of genes
      encoding three glycosyltransferases and an oligosaccharyltransferase (Stt3p
      homologue) resulted in flagellins of decreased molecular masses as evidenced by
      immunoblotting, indicating partial or completely absent glycan structures.
      Deletion of the oligosaccharyltransferase or the glycosyltransferase responsible
      for the transfer of the second sugar in the chain resulted in flagellins that
      were not assembled into flagella filaments, as evidenced by electron microscopy.
      Deletions of the glycosyltransferases responsible for the addition of the third
      and terminal sugars in the glycan were confirmed by mass spectrometry analysis of
      purified flagellins from these mutants. Although flagellated, these mutants had
      decreased motility as evidenced by semi-swarm plate analysis with the presence of
      each additional sugar improving movement capabilities.

PMID- 19400782
TI  - A conserved small RNA promotes silencing of the outer membrane protein YbfM.
AB  - In the past few years an increasing number of small non-coding RNAs (sRNAs) in
      enterobacteria have been found to negatively regulate the expression of outer
      membrane proteins (OMPs) at the post-transcriptional level. These RNAs act under
      various growth and stress conditions, suggesting that one important physiological
      role of regulatory RNA molecules in Gram-negative bacteria is to modulate the
      cell surface and/or to prevent accumulation of OMPs in the envelope. Here, we
      extend the OMP-sRNA network by showing that the expression of the OMP YbfM is
      silenced by a conserved sRNA, designated MicM (also known as RybC/SroB). The
      regulation is strictly dependent on the RNA chaperone Hfq, and mutational
      analysis indicates that MicM sequesters the ribosome binding site of ybfM mRNA by
      an antisense mechanism. Furthermore, we provide evidence that Hfq strongly
      enhances the on-rate of duplex formation between MicM and its target RNA in
      vitro, supporting the idea that a major cellular role of the RNA chaperone is to
      act as a catalyst in RNA-RNA duplex formation.

PMID- 19400783
TI  - Inducer responses of BenM, a LysR-type transcriptional regulator from
      Acinetobacter baylyi ADP1.
AB  - BenM and CatM control transcription of a complex regulon for aromatic compound
      degradation. These Acinetobacter baylyi paralogues belong to the largest family
      of prokaryotic transcriptional regulators, the LysR-type proteins. Whereas BenM
      activates transcription synergistically in response to two effectors, benzoate
      and cis,cis-muconate, CatM responds only to cis,cis-muconate. Here, site-directed
      mutagenesis was used to determine the physiological significance of an unexpected
      benzoate-binding pocket in BenM discovered during structural studies. Residues in
      BenM were changed to match those of CatM in this hydrophobic pocket. Two BenM
      residues, R160 and Y293, were found to mediate the response to benzoate.
      Additionally, alteration of these residues caused benzoate to inhibit activation
      by cis,cis-muconate, positioned in a separate primary effector-binding site of
      BenM. The location of the primary site, in an interdomain cleft, is conserved in
      diverse LysR-type regulators. To improve understanding of this important family,
      additional regulatory mutants were analysed. The atomic-level structures were
      characterized of the effector-binding domains of variants that do not require
      inducers for activation, CatM(R156H) and BenM(R156H,T157S). These structures
      clearly resemble those of the wild-type proteins in their activated muconate
      bound complexes. Amino acid replacements that enable activation without effectors
      reside at protein interfaces that may impact transcription through effects on
      oligomerization.

PMID- 19400784
TI  - Impact of rRNA methylations on ribosome recycling and fidelity of initiation in
      Escherichia coli.
AB  - Ribosomal RNA (rRNA) contains a number of modified nucleosides in functionally
      important regions including the intersubunit bridge regions. As the activity of
      ribosome recycling factor (RRF) in separating the large and the small subunits of
      the ribosome involves disruption of intersubunit bridges, we investigated the
      impact of rRNA methylations on ribosome recycling. We show that deficiency of
      rRNA methylations, especially at positions 1518 and 1519 of 16S rRNA near the
      interface with the 50S subunit and in the vicinity of the IF3 binding site,
      adversely affects the efficiency of RRF-mediated ribosome recycling. In addition,
      we show that a compromise in the RRF activity affords increased initiation with a
      mutant tRNA(fMet) wherein the three consecutive G-C base pairs
      ((29)GGG(31):(39)CCC(41)), a highly conserved feature of the initiator tRNAs,
      were mutated to those found in the elongator tRNA(Met)
      ((29)UCA(31):(39)psiGA(41)). This observation has allowed us to uncover a new
      role of RRF as a factor that contributes to fidelity of initiator tRNA selection
      on the ribosome. We discuss these and earlier findings to propose that RRF plays
      a crucial role during all the steps of protein synthesis.

PMID- 19400785
TI  - Bacillus anthracis HssRS signalling to HrtAB regulates haem resistance during
      infection.
AB  - Bacillus anthracis proliferates to high levels within vertebrate tissues during
      the pathogenesis of anthrax. This growth is facilitated by the acquisition of
      nutrient iron from host haem. However, haem acquisition can lead to the
      accumulation of toxic amounts of haem within B. anthracis. Here, we show that B.
      anthracis resists haem toxicity by sensing haem through the HssRS two-component
      system, which regulates expression of the haem-detoxifying transporter HrtAB. In
      addition, we demonstrate that B. anthracis exhibits elevated HssRS function
      compared with its evolutionary relative Staphylococcus aureus. Elevated haem
      sensing is likely required by B. anthracis due to the significant haem
      sensitivity exhibited by members of the genus Bacilli. We also demonstrate that
      B. anthracis depends on conserved residues within the previously uncharacterized
      sensing domain of the histidine kinase HssS for HssS function. Finally, we show
      that the haem- and HssRS-regulated hrtAB promoter is activated in a murine model
      of anthrax. These results demonstrate the evolutionary conservation of haem
      sensing among multiple Gram-positive bacteria and begin to provide a mechanistic
      explanation for the haem resistance of B. anthracis. Further, these data suggest
      that haem stress is experienced by bacterial pathogens during infection.

PMID- 19400786
TI  - Structural and kinetic analysis of an MsrA-MsrB fusion protein from Streptococcus
      pneumoniae.
AB  - Methionine sulphoxide reductases (Msr) catalyse the reduction of oxidized
      methionine to methionine. These enzymes are divided into two classes, MsrA and
      MsrB, according to substrate specificity. Although most MsrA and MsrB exist as
      separate enzymes, in some bacteria these two enzymes are fused to form a single
      polypeptide (MsrAB). Here, we report the first crystal structure of MsrAB from
      Streptococcus pneumoniae (SpMsrAB) at 2.4 A resolution. SpMsrAB consists of an N
      terminal MsrA domain, a C-terminal MsrB domain and a linker. The linker is
      composed of 13 residues and contains one 3(10)-helix and several hydrogen bonds
      interacting with both MsrA and MsrB domains. Interestingly, our structure
      includes the MsrB domain complexed with an SHMAEI hexa-peptide that is the N
      terminal region of neighbouring MsrA domain. A kinetic analysis showed that the
      apparent K(m) of SpMsrAB for the R-form-substrate was 20-fold lower than that for
      the S-form substrate, indicating that the MsrB domain had a much higher affinity
      for the substrate than the MsrA domain. Our study reveals the first structure of
      the MsrAB by providing insights into the formation of a disulphide bridge in the
      MsrB, the structure of the linker region, and the distinct structural nature of
      active site of each MsrA and MsrB domain.

PMID- 19400787
TI  - BcsQ is an essential component of the Escherichia coli cellulose biosynthesis
      apparatus that localizes at the bacterial cell pole.
AB  - Biofilms are microbial communities characterized by three-dimensional growth
      resulting from the ability of individual cells to adhere to each other as well as
      to produce an extracellular matrix that ensures biofilm physical cohesion.
      Numerous bacteria produce cellulose as a biofilm matrix polymer, a property
      relying on the expression of bacterial cellulose synthesis (Bcs) proteins and
      their post-translational activation upon binding of cyclic di-guanosine mono
      phosphate second messenger (c-di-GMP) produced by diguanylate cyclases. In
      Escherichia coli and other Enterobacteriaceae, two genes of unknown function,
      yhjR and yhjQ, are located upstream of the bcs genes. Here, we show that yhjQ,
      but not yhjR, is essential for cellulose biosynthesis; it has therefore been
      renamed bcsQ. Using a green fluorescent protein (GFP) fusion approach, we
      demonstrate that BcsQ, a MinD homologue, displays a polar localization and that
      cell-to-cell adhesion is initiated through production of cellulose at the BcsQ
      labelled pole. Although we did not detect a similar localization for other Bcs
      proteins, immunogold labelling of cellulose itself at the pole of individual
      bacteria indicates the localized activity of the cellulose biosynthesis
      apparatus. These results therefore suggest that BcsQ could participate in spatial
      restriction of cellulose biosynthesis activity in Enterobacteriaceae.

PMID- 19400788
TI  - AglZ regulates adventurous (A-) motility in Myxococcus xanthus through its
      interaction with the cytoplasmic receptor, FrzCD.
AB  - Myxococcus xanthus moves by gliding motility powered by type IV pili (S-motility)
      and distributed motor complexes (A-motility). The Frz chemosensory pathway
      controls reversals for both motility systems. However, it is unclear how the Frz
      pathway can communicate with these different systems. In this article, we show
      that FrzCD, the Frz pathway receptor, interacts with AglZ, a protein associated
      with A-motility. Affinity chromatography and cross-linking experiments showed
      that the FrzCD-AglZ interaction occurs between the uncharacterized N-terminal
      region of FrzCD and the N-terminal pseudo-receiver domain of AglZ. Fluorescence
      microscopy showed AglZ-mCherry and FrzCD-GFP localized in clusters that occupy
      different positions in cells. To study the role of the Frz system in the
      regulation of A-motility, we constructed aglZ frzCD double mutants and aglZ frzCD
      pilA triple mutants. To our surprise, these mutants, predicted to show no A
      motility (A-S+) or no motility at all (A-S-), respectively, showed restored A
      motility. These results indicate that AglZ modulates a FrzCD activity that
      inhibits A-motility. We hypothesize that AglZ-FrzCD interactions are favoured
      when cells are isolated and moving by A-motility and inhibited when S-motility
      predominates and A-motility is reduced.

PMID- 19400789
TI  - Peptide alarmone signalling triggers an auto-active bacteriocin necessary for
      genetic competence.
AB  - The induction of genetic competence is a strategy used by bacteria to increase
      their genetic repertoire under stressful environmental conditions. Recently,
      Streptococcus pneumoniae has been shown to co-ordinate the uptake of transforming
      DNA with fratricide via increased expression of the peptide pheromone responsible
      for competence induction. Here, we document that environmental stress-induced
      expression of the peptide pheromone competence-stimulating peptide (CSP) in the
      oral pathogen Streptococcus mutans. We showed that CSP is involved in the stress
      response and determined the CSP-induced regulon in S. mutans by microarray
      analysis. Contrary to pneumococcus, S. mutans responds to increased
      concentrations of CSP by cell lysis in only a fraction of the population. We have
      focused on the mechanism of cell lysis and have identified a novel bacteriocin as
      the 'death effector'. Most importantly, we showed that this bacteriocin causes
      cell death via a novel mechanism of action: intracellular action against self. We
      have also identified the cognate bacteriocin immunity protein, which resides in a
      separate unlinked genetic locus to allow its differential regulation. The role of
      the lytic response in S. mutans competence is also discussed. Together, these
      findings reveal a novel autolytic pathway in S. mutans which may be involved in
      the dissemination of fitness-enhancing genes in the oral biofilm.

PMID- 19400790
TI  - Mutational analysis of Escherichia coli sigma28 and its target promoters reveals
      recognition of a composite -10 region, comprised of an 'extended -10' motif and a
      core -10 element.
AB  - Sigma28 controls the expression of flagella-related genes and is the most widely
      distributed alternative sigma factor, present in motile Gram-positive and Gram
      negative bacteria. The distinguishing feature of sigma28 promoters is a long -10
      region (GCCGATAA). Despite the fact that the upstream GC is highly conserved,
      previous studies have not indicated a functional role for this motif. Here we
      examine the functional relevance of the GCCG motif and determine which residues
      in sigma28 participate in its recognition. We find that the GCCG motif is a
      functionally important composite element. The upstream GC constitutes an extended
      -10 motif and is recognized by R91, a residue in Domain 3 of sigma28. The
      downstream CG is the upstream edge of -10 region of the promoter; two residues in
      Region 2.4, D81 and R84, participate in its recognition. Consistent with their
      role in base-specific recognition of the promoter, R91, D81 and D84 are
      universally conserved in sigma28 orthologues. Sigma28 is the second Group 3 sigma
      shown to use an extended -10 region in promoter recognition, raising the
      possibility that other Group 3 sigmas will do so as well.

PMID- 19400792
TI  - Expression of the meningococcal adhesin NadA is controlled by a transcriptional
      regulator of the MarR family.
AB  - Two closely related pathogenic species have evolved in the genus Neisseria: N.
      meningitidis and N. gonorrhoeae, which occupy different host niches and cause
      different clinical entities. In contrast to the pathogen N. gonorrhoeae, N.
      meningitidis is a commensal and only rarely becomes invasive. Little is known
      about the genetic background of the entirely different lifestyles in these
      closely related species. Meningococcal NMB1843 encodes a transcriptional
      regulator of the MarR family. The gonococcal homologue FarR regulates expression
      of farAB, mediating fatty acid resistance. We show that NmFarR also directly
      interacts with NmfarAB. Yet, by contrast to N. gonorrhoeae, no significant
      sensitivity to fatty acids was observed in a DeltafarR mutant due to intrinsic
      resistance of meningococci. Further analyses identified an NmFarR-repressed
      protein absent from N. gonorrhoeae. This protein is the meningococcus-specific
      adhesin and vaccine component NadA that has most likely been acquired by
      horizontal gene transfer. NmFarR binds to a 16 base pair palindromic repeat
      within the nadA promoter. De-repression of nadA resulted in significantly higher
      association of a DeltafarR strain with epithelial cells. Hence NmFarR has gained
      control over a meningococcus-specific gene involved in host colonization and thus
      contributed to divergent niche adaptation in pathogenic Neisseriae.

PMID- 19400791
TI  - Dissection of recognition determinants of Escherichia coli sigma32 suggests a
      composite -10 region with an 'extended -10' motif and a core -10 element.
AB  - Sigma32 controls expression of heat shock genes in Escherichia coli and is widely
      distributed in proteobacteria. The distinguishing feature of sigma32 promoters is
      a long -10 region (CCCCATNT) whose tetra-C motif is important for promoter
      activity. Using alanine-scanning mutagenesis of sigma32 and in vivo and in vitro
      assays, we identified promoter recognition determinants of this motif. The most
      downstream C (-13) is part of the -10 motif; our work confirms and extends
      recognition determinants of -13C. Most importantly, our work suggests that the
      two upstream Cs (-16, -15) constitute an 'extended -10' recognition motif that is
      recognized by K130, a residue universally conserved in beta- and gamma
      proteobacteria. This residue is located in the alpha-helix of sigmaDomain 3 that
      mediates recognition of the extended -10 promoter motif in other sigmas. K130 is
      not conserved in alpha- and delta-/epsilon-proteobacteria and we found that
      sigma32 from the alpha-proteobacterium Caulobacter crescentus does not need the
      extended -10 motif for high promoter activity. This result supports the idea that
      K130 mediates extended -10 recognition. Sigma32 is the first Group 3 sigma shown
      to use the 'extended -10' recognition motif.

PMID- 19400793
TI  - Inhibition of cathelicidin activity by bacterial exopolysaccharides.
AB  - The interaction of bacterial exopolysaccharides, produced by opportunistic lung
      pathogens, with antimicrobial peptides of the innate primate immune system was
      investigated. The exopolysaccharides were produced by Pseudomonas aeruginosa,
      Inquilinus limosus and clinical isolates of the Burkholderia cepacia complex,
      bacteria that are all involved in lung infections of cystic fibrosis patients.
      The effects of the biological activities of three orthologous cathelicidins from
      Homo sapiens sapiens, Pongo pygmaeus (orangutan) and Presbitys obscurus (dusky
      leaf monkey) were examined. Inhibition of the antimicrobial activity of peptides
      was assessed using minimum inhibitory concentration assays on a reference
      Escherichia coli strain in the presence and absence of exopolysaccharides,
      whereas complex formation between peptides and exopolysaccharides was
      investigated by means of circular dichroism, fluorescence spectroscopy and atomic
      force microscopy. Biological assays revealed that the higher the negative charge
      of exopolysaccharides the stronger was their inhibiting effect. Spectroscopic
      studies indicated the formation of molecular complexes of varying stability
      between peptides and exopolysaccharides, explaining the inhibition. Atomic force
      microscopy provided a direct visualization of the molecular complexes. A model is
      proposed where peptides with an alpha-helical conformation interact with
      exopolysaccharides through electrostatic and other non-covalent interactions.

PMID- 19400794
TI  - FtsN-like proteins are conserved components of the cell division machinery in
      proteobacteria.
AB  - In bacteria, cytokinesis is mediated by a ring-shaped multiprotein complex,
      called divisome. While some of its components are widely conserved, others are
      restricted to certain bacterial lineages. FtsN is the last essential cell
      division protein to localize to the division septum in Escherichia coli and is
      poorly conserved outside the enteric bacteria. We have identified a homologue of
      FtsN in the alpha-proteobacterium Caulobacter crescentus and show that it is
      essential for cell division. C. crescentus FtsN is recruited to the divisome
      significantly after cell division initiates and remains associated with the new
      cell poles after cytokinesis is finished. All determinants necessary for
      localization and function are located in a largely unstructured periplasmic
      segment of the protein. Its conserved SPOR-domain, by contrast, is dispensable
      for cytokinesis, although it supports targeting of FtsN to the division site.
      Interestingly, the SPOR-domain is recruited to the division plane when produced
      in isolated form and retains its localization potential in a heterologous host
      background. Searching for proteins that share the characteristic features of FtsN
      from E. coli and C. crescentus, we identified FtsN-like cell division proteins in
      beta- and delta-proteobacteria, suggesting that FtsN is widespread among
      bacteria, albeit highly variable at the sequence level.

PMID- 19400796
TI  - Molecular analysis of restriction endonuclease EcoRII from Escherichia coli
      reveals precise regulation of its enzymatic activity by autoinhibition.
AB  - Bacterial restriction endonuclease EcoRII requires two recognition sites to
      cleave DNA. Proteolysis of EcoRII revealed the existence of two stable domains,
      EcoRII-N and EcoRII-C. Reduction of the enzyme to its C-terminal domain, EcoRII
      C, unleashed the enzyme activity; this truncated form no longer needed two
      recognition sites and cleaved DNA much more efficiently than EcoRII wild-type.
      The crystal structure of EcoRII showed that probably the N-terminal domain
      sterically occludes the catalytic site, thus apparently controlling the cleavage
      activity. Based on these data, EcoRII was the first restriction endonuclease for
      which an autoinhibition mechanism as regulatory strategy was proposed. In this
      study, we probed this assumption and searched for the inhibitory element that
      mediates autoinhibition. Here we show that repression of EcoRII-C is achieved by
      addition of the inhibitory domain EcoRII-N or by single soluble peptides thereof
      in trans. Moreover, we perturbed contacts between the N- and the C-terminal
      domain of EcoRII by site-directed mutagenesis and proved that beta-strand B1 and
      alpha-helix H2 are essential for autoinhibition; deletion of either secondary
      structural element completely relieved EcoRII autoinhibition. This potent
      regulation principle that keeps EcoRII enzyme activity controlled might protect
      bacteria against suicidal restriction of rare unmodified recognition sites in the
      cellular genome.

PMID- 19400795
TI  - A fratricidal mechanism is responsible for eDNA release and contributes to
      biofilm development of Enterococcus faecalis.
AB  - Extracellular DNA (eDNA), a by-product of cell lysis, was recently established as
      a critical structural component of the Enterococcus faecalis biofilm matrix.
      Here, we describe fratricide as the governing principle behind gelatinase (GelE)
      mediated cell death and eDNA release. GFP reporter assays confirmed that GBAP
      (gelatinase biosynthesis-activating pheromone) quorum non-responders (GelE-SprE-)
      were a minority subpopulation of prey cells susceptible to the targeted
      fratricidal action of the quorum responsive predatorial majority (GelE+SprE+).
      The killing action is dependent on GelE, and the GelE producer population is
      protected from self-destruction by the co-production of SprE as an immunity
      protein. Targeted gene inactivation and protein interaction studies demonstrate
      that extracellular proteases execute their characteristic effects following
      downstream interactions with the primary autolysin, AtlA. Finally, we address a
      mechanism by which GelE and SprE may modify the cell wall affinity of
      proteolytically processed AtlA resulting in either a pro- or anti-lytic outcome.

PMID- 19400797
TI  - TagR promotes PpkA-catalysed type VI secretion activation in Pseudomonas
      aeruginosa.
AB  - Type VI secretion systems (T6SSs) contribute to interactions of bacterial
      pathogens and symbionts with their hosts. Previously, we showed that Pseudomonas
      aeruginosa T6S is posttranslationally activated upon phosphorylation of Fha1, an
      FHA domain protein, by PpkA, a membrane-spanning threonine kinase. Herein,
      additional structural, enzymatic and genetic requirements for PpkA-catalysed T6SS
      activation are identified. We found that PpkA plays an essential structural role
      in the T6SS, and that this role is intimately linked to its ability to promote
      secretion and phosphorylate Fha1. Protein localization and protein-protein
      interaction studies show that a complex containing Fha1 and the T6S ATPase, ClpV1
      is recruited to the T6S apparatus in a phosphorylation-dependent manner. The
      mechanism of PpkA activation was also investigated. We identified critical PpkA
      autophosphorylation sites and showed that small molecule-induced dimerization of
      the extracellular domains of PpkA is sufficient to activate the T6SS. Finally, we
      discovered TagR, a component of the T6S posttranslational regulatory pathway that
      functions upstream of PpkA to promote kinase activity. We present a model whereby
      an unknown cue causes dimerization of the extracellular domains of PpkA, leading
      to its autophosphorylation, recruitment of the Fha1-ClpV1 complex,
      phosphorylation of Fha1, and T6SS activation. Our findings should facilitate
      approaches for identifying physiological activators of T6S.

PMID- 19400798
TI  - Mutations in the gene 5 DNA polymerase of bacteriophage T7 suppress the dominant
      lethal phenotype of gene 2.5 ssDNA binding protein lacking the C-terminal
      phenylalanine.
AB  - Gene 2.5 of bacteriophage T7 encodes a ssDNA binding protein (gp2.5) essential
      for DNA replication. The C-terminal phenylalanine of gp2.5 is critical for
      function and mutations in that position are dominant lethal. In order to identify
      gp2.5 interactions we designed a screen for suppressors of gp2.5 lacking the C
      terminal phenylalanine. Screening for suppressors of dominant lethal mutations of
      essential genes is challenging as the phenotype prevents propagation. We select
      for phage encoding a dominant lethal version of gene 2.5, whose viability is
      recovered via second-site suppressor mutation(s). Functional gp2.5 is expressed
      in trans for propagation of the unviable phage and allows suppression to occur
      via natural selection. The isolated intragenic suppressors support the critical
      role of the C-terminal phenylalanine. Extragenic suppressor mutations occur in
      several genes encoding enzymes of DNA metabolism. We have focused on the
      suppressor mutations in gene 5 encoding the T7 DNA polymerase (gp5) as the
      gp5/gp2.5 interaction is well documented. The suppressor mutations in gene 5 are
      necessary and sufficient to suppress the lethal phenotype of gp2.5 lacking the C
      terminal phenylalanine. The affected residues map in proximity to aromatic
      residues and to residues in contact with DNA in the crystal structure of T7 DNA
      polymerase-thioredoxin.

PMID- 19400799
TI  - From alpha to beta: identification of amino acids required for the N
      acetyllactosamine-specific lectin-like activity of bundlin.
AB  - Bundle-forming pili (BFP) promote the adherence of typical enteropathogenic
      Escherichia coli (EPEC) to human intestinal epithelial cells. BFP are polymers of
      bundlin and nine bundlin alleles have been identified in EPEC isolated from
      diverse sources. These alleles are divided into two main groups, alpha and beta,
      based on their amino acid sequences. Alpha bundlins are also N-acetyllactosamine-
      (LacNAc) specific lectins and bind to HEp-2 cells, whereas beta bundlins do not
      display these characteristics. The four surface-exposed regions of amino acid
      sequence heterogeneity between alpha and beta bundlin were therefore investigated
      as potential LacNAc-specific carbohydrate-binding domains in a bundlin. Mutation
      of one of these domains, 137-GENNI-141, in alpha(1) bundlin to that of beta
      bundlin (136-SPDST-140) resulted in BFP that no longer bound to LacNAc or HEp-2
      cells. Conversely, mutating the beta3 bundlin gene to encode the alpha bundlin
      sequence at this domain resulted in the gain of HEp-2 cell adherence. The
      importance of this domain in carbohydrate binding is supported by the finding
      that introducing the mutation GENNI-->GENNT altered the alpha1 bundlin
      carbohydrate-binding specificity from LacNAc to the Lewis X glycan sequence.

PMID- 19400800
TI  - More pieces in the promoter jigsaw: recognition of -10 regions by alternative
      sigma factors.
AB  - Two papers in this issue of Molecular Microbiology from Carol Gross and
      colleagues describe experiments that investigate how two alternative Escherichia
      coli sigma proteins recognize target promoter -10 regions. A combination of
      genetics, biochemistry and bioinformatics is used to show that determinants in
      two adjacent domains of the sigma proteins contact discrete sequence elements in
      the -10 regions.

PMID- 19400801
TI  - Crystal structure of the Vibrio cholerae ferric uptake regulator (Fur) reveals
      insights into metal co-ordination.
AB  - The ferric uptake regulator (Fur) is a metal-dependent DNA-binding protein that
      acts as both a repressor and an activator of numerous genes involved in
      maintaining iron homeostasis in bacteria. It has also been demonstrated in Vibrio
      cholerae that Fur plays an additional role in pathogenesis, opening up the
      potential of Fur as a drug target for cholera. Here we present the crystal
      structure of V. cholerae Fur that reveals a very different orientation of the DNA
      binding domains compared with that observed in Pseudomonas aeruginosa Fur. Each
      monomer of the dimeric Fur protein contains two metal binding sites occupied by
      zinc in the crystal structure. In the P. aeruginosa study these were designated
      as the regulatory site (Zn1) and structural site (Zn2). This V. cholerae Fur
      study, together with studies on Fur homologues and paralogues, suggests that in
      fact the Zn2 site is the regulatory iron binding site and the Zn1 site plays an
      auxiliary role. There is no evidence of metal binding to the cysteines that are
      conserved in many Fur homologues, including Escherichia coli Fur. An analysis of
      the metal binding properties shows that V. cholerae Fur can be activated by a
      range of divalent metals.

PMID- 19400803
TI  - The transcriptional response to cadmium, organic hydroperoxide, singlet oxygen
      and UV-A mediated by the sigmaE-ChrR system in Caulobacter crescentus.
AB  - Caulobacter crescentussigma(E) belongs to the ECF (extracytoplasmic function)
      subfamily of RNA polymerase sigma factors, whose members regulate gene expression
      in response to distinct environmental stresses. During physiological growth
      conditions, data indicate that sigma(E) is maintained in reduced levels due to
      the action of ChrR, a negative regulator of rpoE gene expression and function.
      However, once bacterial cells are exposed to cadmium, organic hydroperoxide,
      singlet oxygen or UV-A irradiation, transcription of rpoE is induced in a
      sigma(E)-dependent manner. Site-directed mutagenesis indicated that residue C188
      in ChrR is critical for the cadmium response while residues H140 and H142 are
      required for the bacterial response to organic hydroperoxide, singlet oxygen and
      UV-A. Global transcriptional analysis showed that sigma(E) regulates genes
      involved in protecting cells against oxidative damages. A combination of
      transcriptional start site identification and promoter prediction revealed that
      some of these genes contain a putative sigma(E)-dependent motif in their upstream
      regions. Furthermore, deletion of rpoE and two sigma(E)-dependent genes (cfaS and
      hsp20) impairs Caulobacter survival when singlet oxygen is constantly generated
      in the cells.

PMID- 19400804
TI  - Perturbation of phosphatidylethanolamine synthesis affects mitochondrial
      morphology and cell-cycle progression in procyclic-form Trypanosoma brucei.
AB  - Phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are the two major
      constituents of eukaryotic cell membranes. In the protist Trypanosoma brucei, PE
      and PC are synthesized exclusively via the Kennedy pathway. To determine which
      organelles or processes are most sensitive to a disruption of normal phospholipid
      levels, the cellular consequences of a decrease in the levels of PE or PC,
      respectively, were studied following RNAi knock-down of four enzymes of the
      Kennedy pathway. RNAi against ethanolamine-phosphate cytidylyltransferase (ET)
      disrupted mitochondrial morphology and ultrastructure. Electron microscopy
      revealed alterations of inner mitochondrial membrane morphology, defined by a
      loss of disk-like cristae. Despite the structural changes in the mitochondrion,
      the cells maintained oxidative phosphorylation. Our results indicate that the
      inner membrane morphology of T. brucei procyclic forms is highly sensitive to a
      decrease of PE levels, as a change in the ultrastructure of the mitochondrion is
      the earliest phenotype observed after RNAi knock-down of ET. Interference with
      phospholipid synthesis also impaired normal cell-cycle progression. ET RNAi led
      to an accumulation of multinucleate cells. In contrast, RNAi against choline
      /ethanolamine phosphotransferase, which affected PC as well as PE levels, caused
      a cell division phenotype characterized by non-division of the nucleus and
      production of zoids.

PMID- 19400805
TI  - YgdE is the 2'-O-ribose methyltransferase RlmM specific for nucleotide C2498 in
      bacterial 23S rRNA.
AB  - The rRNAs of Escherichia coli contain four 2'-O-methylated nucleotides. Similar
      to other bacterial species and in contrast with Archaea and Eukaryota, the E.
      coli rRNA modifications are catalysed by specific methyltransferases that find
      their nucleotide targets without being guided by small complementary RNAs. We
      show here that the ygdE gene encodes the methyltransferase that catalyses 2'-O
      methylation at nucleotide C2498 in the peptidyl transferase loop of E. coli 23S
      rRNA. Analyses of rRNAs using MALDI mass spectrometry showed that inactivation of
      the ygdE gene leads to loss of methylation at nucleotide C2498. The loss of ygdE
      function causes a slight reduction in bacterial fitness. Methylation at C2498 was
      restored by complementing the knock-out strain with a recombinant copy of ygdE.
      The recombinant YgdE methyltransferase modifies C2498 in naked 23S rRNA, but not
      in assembled 50S subunits or ribosomes. Nucleotide C2498 is situated within a
      highly conserved and heavily modified rRNA sequence, and YgdE's activity is
      influenced by other modification enzymes that target this region.
      Phylogenetically, YgdE is placed in the cluster of orthologous groups COG2933
      together with S-adenosylmethionine-dependent, Rossmann-fold methyltransferases
      such as the archaeal and eukaryotic RNA-guided fibrillarins. The ygdE gene has
      been redesignated rlmM for rRNA large subunit methyltransferase M.

PMID- 19400802
TI  - Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus.
AB  - Fungi are a rich source of bioactive secondary metabolites, and mushroom-forming
      fungi (Agaricomycetes) are especially known for the synthesis of numerous
      bioactive and often cytotoxic sesquiterpenoid secondary metabolites. Compared
      with the large number of sesquiterpene synthases identified in plants, less than
      a handful of unique sesquiterpene synthases have been described from fungi. Here
      we describe the functional characterization of six sesquiterpene synthases (Cop1
      to Cop6) and two terpene-oxidizing cytochrome P450 monooxygenases (Cox1 and Cox2)
      from Coprinus cinereus. The genes were cloned and, except for cop5, functionally
      expressed in Escherichia coli and/or Saccharomyces cerevisiae. Cop1 and Cop2 each
      synthesize germacrene A as the major product. Cop3 was identified as an alpha
      muurolene synthase, an enzyme that has not been described previously, while Cop4
      synthesizes delta-cadinene as its major product. Cop6 was originally annotated as
      a trichodiene synthase homologue but instead was found to catalyse the highly
      specific synthesis of alpha-cuprenene. Coexpression of cop6 and the two
      monooxygenase genes next to it yields oxygenated alpha-cuprenene derivatives,
      including cuparophenol, suggesting that these genes encode the enzymes for the
      biosynthesis of antimicrobial quinone sesquiterpenoids (known as lagopodins) that
      were previously isolated from C. cinereus and other Coprinus species.

PMID- 19400806
TI  - Organization of the genes encoding the biosynthesis of actagardine and
      engineering of a variant generation system.
AB  - The biosynthetic pathway of the type B lantibiotic actagardine (formerly
      gardimycin), produced by Actinoplanes garbadinensis ATCC31049, has been cloned,
      sequenced and annotated. The gene cluster contains the gene garA that encodes the
      actagardine prepropeptide, a modification gene garM, involved in the dehydration
      and cyclization of the prepeptide, several putative transporter and regulatory
      genes as well as a novel luciferase-like monooxygenase gene designated garO.
      Expression of these genes in Streptomyces lividans resulted in the production of
      ala(0)-actagardine while deletion of the garA gene from A. garbadinensis
      generated a strain incapable of producing actagardine. Actagardine production was
      successfully restored however, by the delivery of the plasmid pAGvarX. This
      plasmid contains an engineered cassette of the actagardine encoding gene garA and
      offers an alternative route to generating extensive libraries of actagardine
      variants. Using this plasmid, an alanine scanning library has been constructed
      and the mutants analysed. Further modifications include the removal of the novel
      garO gene from A. garbadinensis. Deletion of this gene resulted in the production
      of deoxy variants of actagardine, demonstrating that the formation of the
      sulfoxide group is enzyme catalysed and not a spontaneous chemical modification
      as previously believed.

PMID- 19400807
TI  - The LetA-RsmYZ-CsrA regulatory cascade, together with RpoS and PmrA, post
      transcriptionally regulates stationary phase activation of Legionella pneumophila
      Icm/Dot effectors.
AB  - Legionella pneumophila utilize the Icm/Dot type-IV secretion system to
      translocate effector proteins into host cells. Some of these effectors were shown
      before to be regulated at the transcriptional level by the PmrAB and CpxRA two
      component systems. In addition, the stationary phase-related regulators LetA and
      CsrA, which are both members of the same post-transcriptional regulatory cascade,
      were shown to be involved in L. pneumophila virulence. In this report, we
      identified two small non-coding RNAs which are part of the LetA-CsrA regulatory
      cascade and three effector-encoding genes which are directly controlled by this
      regulatory system. We found that the small non-coding RNAs RsmY and RsmZ, were
      upregulated by LetA at stationary phase, and relieve the repression of CsrA from
      its target genes. The three effector-encoding genes were found to be post
      transcriptionally upregulated at stationary phase and to contain CsrA regulatory
      elements that were found to be essential for their stationary phase activation.
      In addition, rsmY and rsmZ were found to be regulated by the RpoS sigma-factor
      and the csrA encoding gene was found to be regulated by PmrA. Our results
      demonstrate that L. pneumophila effectors are regulated at both the
      transcriptional and the post-transcriptional levels by a complicated regulatory
      network.

PMID- 19400808
TI  - Stimulation of the potassium sensor KdpD kinase activity by interaction with the
      phosphotransferase protein IIA(Ntr) in Escherichia coli.
AB  - Proteins EI(Ntr), NPr and IIA(Ntr) form a phosphoryl group transfer chain (Ntr
      PTS) working in parallel to the phosphoenolpyruvate:carbohydrate
      phosphotransferase system (transport-PTS) in Escherichia coli. Recently, it was
      shown that dephosphorylated IIA(Ntr) binds and inhibits TrkA, a low-affinity
      potassium transporter. Here we report that the Ntr-PTS also regulates expression
      of the high-affinity K+ transporter KdpFABC, which rescues K+ uptake at limiting
      K+ concentrations. Transcription initiation at the kdpFABC promoter is positively
      controlled by the two-component system KdpD/KdpE in response to K+ availability.
      We found that kdp promoter activity is stimulated by the dephosphorylated form of
      IIA(Ntr). Two-hybrid data and biochemical analysis revealed that IIA(Ntr)
      interacts with sensor kinase KdpD and stimulates kinase activity, resulting in
      increased levels of phosphorylated response regulator KdpE. The data suggest that
      exclusively dephosphorylated IIA(Ntr) binds and activates KdpD. As there is cross
      talk between the Ntr-PTS and the transport-PTS, carbon source utilization affects
      kdpFABC expression. Expression is enhanced, when cells utilize preferred
      carbohydrates like glucose, which results in preferential dephosphorylation of
      the transport-PTS and also of IIA(Ntr). Taken together, the data show that the
      Ntr-PTS has an important role in maintaining K+ homeostasis and links K+ uptake
      to carbohydrate metabolism.

PMID- 19400809
TI  - Strongyloides hyperinfection syndrome and transplantation: a preventable,
      frequently fatal infection.

PMID- 19400810
TI  - Septic arthritis and acute hematogenous osteomyelitis in childhood at a tertiary
      hospital in Japan.
AB  - BACKGROUND: The aim of the present study was to describe the clinical features of
      septic arthritis (SA) and acute hematogenous osteomyelitis (AHO) in children and
      to assess the impact of health-care-associated infections and antimicrobial
      resistance. METHODS: A retrospective review of medical records of children
      presenting to Osaka City General Hospital with SA and AHO was undertaken during
      an 85 month period. The following data were assessed: location at onset, age and
      gender, risk factors, involved joints and/or bones, symptoms and time of
      presentation, causative agents and sensitivity to antibiotics, treatments and
      late complications. RESULTS: There were four health-care-associated (HCAI) and 20
      community-acquired infections (CAI). The latency period from initial presentation
      to diagnosis was relatively longer in HCAI than CAI. The most common pathogen was
      methicillin-resistant Staphylococcus aureus (MRSA). Twenty percent of CAI
      patients and half of the HCAI patients were treated empirically for MRSA. All
      patients with complications had MRSA infection. CONCLUSION: Many pediatric
      patients with SA were not treated initially with optimal antibiotics. Although
      surgical intervention was almost inevitably required, selection and
      administration of effective antibiotics was necessary not only to cure the
      current infection but also to prevent metastatic infection. In Japan, empiric
      treatment of SA and AHO should include first-line antibiotics against MRSA.

PMID- 19400811
TI  - Short-term efficacy of tacrolimus ointment and impact on quality of life.
AB  - BACKGROUND: Topical calcineurin inhibitor (TCI) was reported to be an effective
      therapeutic agent for patients with atopic dermatitis (AD), for not only
      improving clinical findings but also for reducing pruritus. Recently in Japan
      tacrolimus ointment (0.03%) as a TCI was approved for use in children aged > or
      =2 years. There have been no reports, however, on the impact of TCI on quality of
      life (QOL) in pediatric AD in Japan. The purpose of the present study was
      therefore to evaluate the efficacy of tacrolimus ointment (0.03%) in the short
      term and the impact on patient QOL. METHODS: A total of 30 pediatric patients
      with AD, whose skin problems were not sufficiently controlled by mid-high potency
      topical glucocorticosteroids, were enrolled. Efficacy was assessed on score of
      cutaneous findings, pruritus, sleeping disorder, and QOL. RESULTS: Three patients
      discontinued because of skin burning (n = 1), generalized herpes infection (n =
      1), and feeling of lack of efficacy (n = 1), leaving a final total of 27 patients
      who were evaluated. Significant improvements in clinical findings, pruritus, and
      sleeplessness were observed within 1 week of treatment and consequently each QOL
      category was also improved. These improvements continued for the duration of the
      study. CONCLUSIONS: Tacrolimus ointment therapy is rapidly effective for not only
      clinical symptoms (cutaneous findings, pruritus and sleeplessness) but also in
      QOL of AD pediatric patients aged > or =2 years.

PMID- 19400812
TI  - Changes in salivary and fecal secretory IgA in infants under different feeding
      regimens.
AB  - BACKGROUND: One of the causes of food allergy in infancy is assumed to be
      immunological immaturity of the intestinal tract. The purpose of the present
      study was to examine changes in salivary and fecal secretory IgA (sIgA) levels in
      infants under different feeding regimens to evaluate the immunological maturity
      of the intestinal tract. METHODS: Thirty-four infants were enrolled at the
      beginning of the study, and 28 of them were followed up to 12 months of age. sIgA
      was measured on enzyme-linked immunosorbent assay. Changes in the levels of
      salivary and fecal sIgA during the first 12 months of life were compared among
      formula-fed infants (F group), breast-formula-fed infants (BF group) and breast
      fed infants (B group). RESULTS: Salivary sIgA was detected in almost all neonates
      on the day of birth. Salivary sIgA was significantly higher in the F group than
      in the BF group at the age of 2 months (P < 0.05). Fecal sIgA appeared from day 2
      and rapidly increased at 1 month of age in all groups. B group infants had
      significantly higher level of fecal sIgA than F group infants at 1 month of age
      (P < 0.05). CONCLUSIONS: The level of salivary sIgA hardly changed, whereas fecal
      sIgA was significantly influenced by intake of breast milk.

PMID- 19400813
TI  - Prevalence and predictors of immunization in a health insurance plan in a
      developing country.
AB  - BACKGROUND: The aim of the present study was to describe rates and predictors of
      compliance with immunization schedule among children enrolled in the Health
      Insurance Plan of the American University of Beirut. METHODS: Charts were
      reviewed for 774 children, and 154 parents underwent a randomly selected sample
      survey of demographic characteristics, parental behavior and attitudes, and
      health-care system variables. RESULTS: The overall compliance rate was 49.9%. By
      age 4 years, 54.6% of children had taken the required vaccines on time. A total
      of 86% of parents whose children were non-compliant had recall bias. Age of the
      child (older), incorrect parental perception of immunization status, mother's low
      education, and use of other health-care facility, were associated with non
      compliance. CONCLUSIONS: Health education about vaccines should be promoted, with
      an emphasis on high-risk groups. Recall systems and other tools to increase
      immunization coverage may have an effective role, but in developing countries,
      aspects such as wide availability of computers and addresses need to be secured
      before such implementation.

PMID- 19400814
TI  - Interferon-alpha for alarming hemangiomas in infants: experience of a single
      institution.
AB  - BACKGROUND: Hemangioma is the most common tumor in infancy. 'Alarming
      hemangiomas' refer to the lesions that potentially impair vital structures or
      cause life-endangering complications, and which warrant vigorous treatment.
      Interferon-alpha has been used for alarming hemangiomas at Mackay Memorial
      Hospital, Taipei, Taiwan, since 1994. METHODS: The records of 21 consecutive
      infants treated between January 1994 and December 2005 were retrospectively
      reviewed. The initial dose of interferon-alpha was 50 000 IU/kg per day, which
      was increased to 100,000 IU/kg per day in the second week of therapy if
      tolerated. It was tapered depending on response, with total treatment lasting no
      longer than 12 months. Treatment response was evaluated depending on the size of
      the lesion and resolution of complications. RESULTS: The duration of therapy
      ranged from 6 to 12 months. Six patients (29%) had a reduction in mass of > or
      =25% after 1 month of therapy. Twenty patients (95%) had achieved a decrease in
      size of 50% by 12 months, and 15 (71%) had total involution of lesions by a
      median age of 13.5 months (range 7-50 months). Only mild and transient adverse
      effects were encountered. No neurologic complications occurred. CONCLUSIONS:
      Interferon-alpha appears to be an effective and well-tolerated treatment for
      alarming hemangiomas in infancy.

PMID- 19400815
TI  - Relationship between body image and lifestyle factors in Japanese adolescent
      girls.
AB  - BACKGROUND: Body image, defined here as an inaccurate perception of personal
      bodyweight, plays a significant role in the development of obesity, eating
      problems and eating disorders. Certain lifestyle factors may influence an
      individual's body image, but current knowledge is based mainly on studies in
      Western populations. METHODS: The associations between body image and lifestyle
      factors were investigated in samples of the Japanese female adolescent
      population. RESULTS: Respondents who reported that they ate meals slowly (odds
      ratio [OR] 1.81, P < 0.001) or only consumed small amounts of food (OR 3.17, P <
      0.001) were more likely to underestimate their body image, as determined by their
      body mass index, than eaters who had average behavior for this age group.
      Individuals who reported eating faster (OR 1.47, P < 0.001) or consuming large
      amounts (OR 1.67, P < 0.001); those who do not eat breakfast on a daily basis (OR
      1.35, P = 0.006); those who go to bed later than the average time for this age
      group (OR 1.38, P < 0.001) or sleep <7 h (OR 1.40, P < 0.001) and those
      individuals who rarely exercise (OR 1.27, P = 0.03) were more likely to
      overestimate their body image, as determined by BMI, compared with those who had
      average eating, sleeping and exercise behaviors for this age group. CONCLUSIONS:
      Variation from the norm in eating, sleeping and exercise behaviors showed a
      relationship with a distorted perception of body image in Japanese adolescent
      girls. These findings are of potential importance in understanding the underlying
      mechanisms involved in the development of body image and for exploring
      interventional approaches.

PMID- 19400816
TI  - Extended-stay hospitalization for childhood asthma in Japan.
AB  - BACKGROUND: While recent advances in asthma management have enabled adequate
      control to be frequently achieved in outpatient settings, children whose asthma
      remains poorly controlled despite outpatient treatment are often referred to
      extended-stay hospitals. The aim of the present study was to examine trends
      concerning extended-stay hospitalization and to evaluate the present status of
      this approach. METHODS: A retrospective study was conducted to assess changes in
      the number of admissions among 408 children with extended stays at Kamiamakusa
      General Hospital between 1989 and 2005. Medical and laboratory data of 236
      patients admitted since 1994 were obtained from clinical records. RESULTS: The
      number of children with extended-stay hospitalizations since 2000 declined
      dramatically compared with the early 1990s, while the percentage of patients with
      complications of childhood asthma, such as severe atopic dermatitis, school
      absenteeism, and obesity, have increased significantly in the recent past.
      Practical benefits of extended-stay hospitalization were demonstrated by
      significant improvement of exercise performance and measurement of pulmonary
      function parameters and serum IgE concentrations by time of discharge. In
      addition to improvement in asthmatic symptoms, maintenance drug requirements and
      frequency of school absenteeism were reduced. CONCLUSIONS: The medical mission of
      extended-stay hospitalizations is currently limited due to the availability of
      improved pharmacotherapy. Some patients, however, with exceptionally severe
      asthma or psychological problems that interact with their medical condition still
      fare poorly under outpatient care and could benefit from group care. Further
      study is needed to identify the components of long-term programs essential to
      produce change.

PMID- 19400817
TI  - Placental findings in malnourished term neonates.
AB  - BACKGROUND: The aim of the present study was to investigate placental pathologies
      in malnourished term neonates. METHODS: A group of term newborns was evaluated at
      birth for fetal malnutrition (FM) using the Clinical Assessment of Nutritional
      Status (CANS) score. The study group consisted of 37 malnourished neonates and 13
      well-nourished newborns, including their placentas. Infants with FM were
      subdivided into two groups: appropriate for gestational age (AGA) and small for
      gestational age (SGA). RESULTS: The proportion of subjects having antepartum
      complications was 18.9% in the FM group, whereas none was found in the control
      group. Similarly, a significant portion, 83.8% of the study group, had gross
      placental abnormalities, while the control group had none. The placental
      microscopic findings in the study group included perivillous fibrin deposition,
      calcification, necrosis, retroplacental hematoma, and infarction. In contrast,
      the control group had only perivillous fibrin deposition and calcification.
      Placental histopathological findings between FM term AGA and SGA neonates were
      also compared, and no statistically significant differences were found (P <
      0.05). CONCLUSIONS: Placental findings in malnourished term AGA neonates are not
      different from findings documented in malnourished SGA cases, but they are
      different from those in well-nourished term AGA newborns.

PMID- 19400818
TI  - Epidural steroid injection--how should the indications for use be derived:
      systematic review or basic science?

PMID- 19400820
TI  - Retraction. Regarding: Walid MS, Donahue SN, Darmohray DM, Hyer LA Jr, Robinson
      JS Jr. The fifth vital sign-what does it mean? Pain Pract. 2008;6:417-422.

PMID- 19400821
TI  - Relationship between maternal and newborn anthropometric measurements in Sudan.
AB  - BACKGROUND: The aim of the present study was to investigate the relationship
      between maternal and newborn anthropometry. METHODS: In 1000 Sudanese mothers and
      newborns anthropometric measurements were taken within 24 h of birth. The
      relationship between maternal characteristics including age, years of education,
      social class and anthropometry, and newborn characteristics including gestational
      age, weight, body length, body circumference and skin-fold thickness, was
      investigated on multiple regression with backward selection, and multivariate
      anova (where appropriate) to identify the most important associations. RESULTS:
      Maternal age and anthropometry were significantly associated with newborn
      anthropometry to a variable extent. The strongest associations (R2 > 5-6%) were
      found for mid-arm circumference, supine length and birthweight. The postpartum
      maternal lean body mass (LBM) was significantly associated with birthweight, body
      length and body circumference (P < 0.001), while skin-fold thickness was mainly
      associated with maternal age and maternal body mass index (BMI). Gestational age
      was only weakly associated with the maternal height (R2 > 1.3%) and the
      association between maternal anthropometry and the ponderal index (PI) of the
      newborn was negligible (R2 < 1%). Maternal education was significantly associated
      with birthweight and body circumference (except the abdominal), and the PI and
      the latter increased significantly with increasing number of years of education.
      No association between social class and newborn anthropometry was obtained.
      CONCLUSION: There was a significant association between maternal LBM and newborn
      size and between maternal BMI and newborn fat stores. Maternal education and not
      social class was associated with newborn size.

PMID- 19400822
TI  - Effect of passive smoking on growth and infection rates of breast-fed and non
      breast-fed infants.
AB  - BACKGROUND: The aim of the present study was to determine the effect of passive
      tobacco smoking on growth and infection rate of infants, and to evaluate whether
      breast-feeding might be protective against harmful effects of cigarette smoke.
      METHODS: A cross-sectional study on 254 6-7-month-old infants was carried out. A
      questionnaire was given to mothers; and infants' head circumference, bodyweight,
      height, and urinary cotinine levels were measured. RESULTS: Multivariate analysis
      of factors influencing lower respiratory tract infections showed that smoking
      mothers increased the rate by 9.1-fold; breast-feeding decreased it by 3.3-fold;
      formula feeding at birth increased it by a factor of 15.2; another smoker at home
      increased it by a factor of 40.1. Multivariate analysis of factors influencing
      upper respiratory tract infections showed that smoking mothers increased the rate
      by a factor of 23; early formula feeding increased it by a factor of 62; breast
      feeding decreased it by a factor of 5; smoking fathers increased it by a factor
      of 15. Multivariate analysis of factors influencing otitis media found that
      smoking mothers and fathers increased it by a factor of 9.4 and 6.15,
      respectively, and breast-feeding decreased it by a factor of 5.4. CONCLUSION:
      Tobacco smoke exposure of infants has negative consequences on growth, otitis
      media, and upper and lower respiratory tract infections. Breast-feeding promoted
      the growth of infants who were passively exposed to tobacco smoke and protected
      them against infections. Smoking should not be permitted in households with
      infants. When this is impossible, breast-feeding should be promoted to protect
      the infants against the health hazards of passive smoking.

PMID- 19400823
TI  - Autoimmune characteristics in Japanese children diagnosed with type 1 diabetes
      before 5 years of age.
AB  - BACKGROUND: Several studies have shown that the autoimmune features in young
      children with type 1 diabetes differ from those in older pediatric patients as
      well as adults. The purpose of the present study was to examine the prevalence of
      beta-cell autoantibodies, glutamic acid decarboxylase antibodies (GADA), and
      antibodies to the protein tyrosine phosphatase-related molecule IA-2 (IA-2A), at
      the time of diagnosis in Japanese children with type 1 diabetes who were younger
      than 5 years at diagnosis. METHODS: Subjects consisted of 23 Japanese children
      (nine boys, 14 girls), 3.1 +/- 1.3 years of age at diagnosis (range, 1.1-4.8
      years). The majority had severe metabolic decompensation accompanied by complete
      absence of beta-cell function at diagnosis. We found 41.7% to have suffered viral
      infections before disease onset. RESULTS: The prevalence of antibodies to GAD and
      IA-2 at diagnosis in these subjects was significantly lower than those in older
      patients diagnosed after 5 years of age (31.6 % vs 86.3% and 47.1% vs 82.5%, P <
      0.0001 and P = 0.0064, respectively). Among 17 patients in whom both antibodies
      were measured, only two (11.8%) had both GADA and IA-2A, three (17.6%) had GADA
      alone, six (35.3%) had IA-2A alone, and six (35.3%) had neither GADA nor IA2-A.
      CONCLUSIONS: Non-autoimmune mechanisms or age-related differences in autoimmunity
      could be involved in the pathogenesis of diabetes in young patients.

PMID- 19400824
TI  - Macrophage inflammatory protein-1beta and interleukin-8 associated with
      idiopathic steroid-sensitive nephrotic syndrome.
AB  - BACKGROUND: The cytokines associated with idiopathic steroid-sensitive nephrotic
      syndrome (ISSNS) have not been identified definitively, because previous studies
      had variable sampling and population heterogeneity. To clarify the cytokines
      involved, serum cytokine levels were measured using uniform sampling in a
      homogeneous population. METHODS: Five children meeting the following criteria
      were included: (i) ISSNS; (ii) selectivity index <0.1; (iii) paired sera obtained
      in the nephrotic phase before steroid treatment (STx; group A) and in the
      remission phase under STx (group B); (iv) no infection; and (v) no
      immunosuppressant. Control groups were as follows: group C, four children with
      ISSNS in the remission phase without STx; group D, five with normal urinalysis;
      group E, five with symptomatic secondary nephrotic syndrome before STx. Cytokine
      levels were measured using bead-based assay. RESULTS: Serum macrophage
      inflammatory protein-1beta (MIP-1beta) levels were higher in group B compared to
      group A, and group C was lower than groups A and B. Serum interleukin-8 (IL-8)
      levels were higher in group A than in groups B and C, and groups B and C did not
      differ. With regard to both cytokine levels, there were no differences between
      groups C and D, and groups A and E. CONCLUSION: Serum MIP-1beta and IL-8 are
      associated with the clinical status of ISSNS in children. A relationship between
      MIP-1beta and ISSNS has not been previously reported. The mechanism by which MIP
      1beta and IL-8 affect ISSNS is unclear. Nevertheless, the present findings are an
      interesting starting point for further investigations into the pathophysiology of
      ISSNS in children.

PMID- 19400825
TI  - Survival and late effects on development of patients with infantile brain tumor.
AB  - BACKGROUND: Most infants with brain tumor may have a poor prognosis. The aim of
      the present study was to retrospectively analyze the survival and outcome with
      regard to mental and physical development in 11 subjects with brain tumor; these
      tumors were diagnosed when the patients were under 1 year of age. METHODS: The
      histological diagnoses of these tumors were astrocytoma, n = 3; pineocytoma, n =
      2; teratoma, n = 1; ependymoma, n = 1; atypical teratoid/rhabdoid tumor, n = 1;
      glioblastoma, n = 1; medulloblastoma, n = 1; and choroid plexus papilloma, n = 1.
      Surgical resection was performed in eight patients, and adjuvant chemotherapy was
      administered to all except one patient with choroid plexus papilloma.
      Radiotherapy was additionally performed for four of the 10 chemotherapy patients.
      RESULTS: Six patients survived. Among the surviving patients, five were under no
      treatment for 50-167 months after the diagnosis (median duration, 89 months),
      while one received chemotherapy for 20 months. Five patients exhibited mental
      retardation, and one patient experienced normal development after surgical
      removal of his choroid plexus papilloma. Diencephalic syndrome developed in one
      patient with pilomyxoid astrocytoma that necessitated hormone replacement
      therapy, and bodyweight over +2 SD was observed in two patients. The remaining
      five patients died 11-111 months after diagnosis (median duration, 24 months).
      CONCLUSION: The prognosis of infantile brain tumor with regard to mortality and
      developmental outcome remains poor. Furthermore, survivors require comprehensive
      medical and social support for an extended period.

PMID- 19400826
TI  - Elevated intracellular calcium in neutrophils in patients with Down syndrome.
AB  - BACKGROUND: Neutrophils of patients with Down syndrome (DS) are known to have
      numerous abnormalities associated with diminished resistance to infection. The
      intracellular calcium (Ca(2+)i) acts as a second messenger and regulates diverse
      functions in many cell types. The purpose of the present study was to compare the
      intracellular calcium concentration ([Ca(2+)]i) at baseline and stimulated
      conditions in DS patients and in normal subjects to investigate [Ca(2+)]i
      regulation in neutrophils. METHODS: The study group consisted of 27 subjects with
      DS (age, 8.6 +/- 4.6 years) and 14 healthy subjects (age, 12.0 +/- 3.9 years).
      Using a fluorescent probe, fura-2, the baseline levels and changes in [Ca(2+)]i
      were examined after stimulation of neutrophils with N-formyl-methionyl-leucyl
      phenylalanine (fMLP). RESULTS: At baseline, the [Ca(2+)]i of neutrophils from DS
      subjects was significantly higher than that of the controls (70.6 +/- 28.0 nmol/L
      vs 44.4 +/- 16.0 nmol/L, P < 0.01). The absolute [Ca(2+)]i after addition of fMLP
      in the DS subjects was also significantly higher than that of the control group
      (250 +/- 91 nmol/L vs 167 +/- 60 nmol/L, respectively: P < 0.01). The neutrophils
      from the DS subjects had a consistently and significantly prolonged response to
      fMLP as compared to the neutrophils of control subjects. CONCLUSIONS: The higher
      [Ca(2+)]i and the prolonged response of [Ca(2+)]i to fMLP appear to be phenotypic
      traits of neutrophils in subjects with DS. This suggests intrinsic cellular
      defects in DS.

PMID- 19400827
TI  - Clinical impact of altered immunoglobulin levels in Henoch-Schonlein purpura.
AB  - BACKGROUND: The aim of the present study was the identification of immunological
      features, present at the time of diagnosis, that would predict the severity of
      Henoch-Schonlein purpura and its outcome. METHODS: A cohort study was carried out
      in a tertiary pediatric hospital of 69 children with Henoch-Schonlein purpura, in
      whom serum complement components C3, C4 and IgA, IgM, IgG were repeatedly
      determined. RESULTS: During the acute phase of the disease in 54/69 patients
      (78.3%) immunological imbalances were observed. In 24/54 cases (44.4%) certain
      complications involving the kidneys and the gastrointestinal tract were noted as
      opposed to in 3/15 children (20%) without immunologic abnormalities. In 50/69
      children (72.5%), elevated serum IgA was detected and 16 of them (32%) developed
      renal involvement while only 1/19 children (5.3%) with normal IgA concentration
      had renal involvement. Considering separately the group of 9/69 children (13%)
      with increased IgM and those with normal IgM levels (53/69; 76.8%), irrespective
      of IgA and IgG concentration, we found a comparable percentage of children who
      had both renal and intestinal involvement without, however, developing severe
      complications, which were exclusively seen in patients with increased IgA (5/7
      children) and reduced IgM levels. Serum C3 fraction was elevated in 26 children
      (37.7%) and in 73% of cases it was associated with increased serum IgA values.
      CONCLUSION: Renal involvement was seen in 32% of children with increased IgA
      values. Most importantly, elevated IgA concentration along with reduced IgM
      levels was associated with higher prevalence of severe complications.

PMID- 19400828
TI  - Dermatological signs in Wilson's disease.
AB  - BACKGROUND: Because no data on skin and mucosal findings of patients with
      Wilson's disease have been published so far, the aim of the present study was to
      investigate the prevalence of mucosal and skin findings in childhood Wilson's
      disease and to determine its specific dermatological findings, if any exist.
      METHODS: Thirty-seven 4-17-year-old children with Wilson's disease were included.
      A complete skin, scalp skin, mucous membrane and nail examination was performed.
      RESULTS: Of the children, 26 (70.3%) had at least one dermatological finding.
      Twenty-five (67.6%), five (13.5%), nine (24.3%) had at least one skin, mucosal
      and nail finding, respectively. The most prevalent dermatological diagnosis of
      the Wilson's disease patients was xerosis (45.7%). The presence of dermatological
      findings was not related to drug usage, severity of the disease, or malnutrition.
      The duration of the disease was not different in patients with or without
      dermatological findings. The frequency of skin findings alone, however, was high
      in relatively newly diagnosed patients (<2 years). CONCLUSION: Dermatologist
      should be aware of the various dermatological manifestations of Wilson's disease,
      because a careful and objective skin, mucosa, nail and hair examination may be
      indicative of a diagnosis of Wilson's disease, particularly in early cases.

PMID- 19400829
TI  - Clinical features of neonatal sepsis caused by resistant Gram-negative bacteria.
AB  - BACKGROUND: Clinical features and outcomes of neonatal sepsis caused by resistant
      Gram-negative bacteria are not well described in Jordan. The aim of the present
      study was therefore to describe microbiology and clinical features, laboratory
      findings and outcomes of early- and late-onset Gram-negative neonatal sepsis.
      METHODS: All patients with Gram-negative bacteremia between July 2003 and June
      2005 were retrospectively included. Resistance profiles, clinical features and
      outcomes of early and late-onset neonatal sepsis were compared. RESULTS: A total
      of 79 patients (after excluding all nine cases of Gram-positive bloodstream
      infection (BSI) were identified as having Gram-negative BSI (25 had early-onset
      and 54 had late-onset neonatal sepsis). Respiratory distress, metabolic acidosis
      and requirement of ventilation were found in 74.7%, 40.5%, and 58.2%,
      respectively. Hypotension was found in 22.9% of patients. Klebsiella pneumoniae
      was responsible for 43 cases (54.4.2%). Klebsiella pneumoniae resistance rates to
      ampicillin and ceftazidime were 100% and 50%, respectively. Mortality rate was
      30.9%. Forty-eight percent of deaths occurred within 3 days of sepsis. Meningitis
      was diagnosed in five cases. Elevated C-reactive protein (CRP) and
      thrombocytopenia were seen in 28% and 24% of infants with early-onset sepsis,
      respectively, and in 79.6%, 59.3% of infants with late-onset sepsis respectively.
      CONCLUSION: Both early- and late-onset neonatal sepsis are caused by highly
      resistant Gram-negative bacteria. Mortality of sepsis is high. Elevated CRP and
      thrombocytopenia is seen more commonly in late-onset neonatal sepsis.

PMID- 19400830
TI  - Molecular pathogenesis of Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer
      which is twice as lethal as melanoma as more than one-third of MCC patients will
      die from this cancer. Although MCC, which primarily affects elderly and immune
      suppressed individuals, is very rare to date, its incidence is rapidly
      increasing. In contrast to the immense progress that has been made in the
      elucidation of the molecular pathogenesis of other cancer entities, until
      recently there were no clear-cut indications which events drive the
      carcinogenesis of MCC. Important findings published last year have changed this
      radically. Hypermethylation of the p14(ARF) promoter and a striking correlation
      between expression of p63 and the clinical course of MCC have been reported. Most
      important, however, is the discovery that MCC development in the majority of
      cases is preceded by the integration of genomic sequences of the hitherto unknown
      Merkel cell polyomavirus (MCPyV). Now a fundamental improvement in the
      understanding of MCC pathogenesis as well as the development of new therapeutic
      approaches based on this knowledge appear to be possible within the near future.

PMID- 19400831
TI  - Extracellular matrix in cutaneous ageing: the effects of 0.1% copper-zinc
      malonate-containing cream on elastin biosynthesis.
AB  - Cutaneous ageing, as visualized at the exposed areas of skin, reflects dramatic
      alterations in the structure and function of the extracellular matrix of
      connective tissues. Among them, the elastic fibre network, which is responsible
      for the physiological elasticity and resilience of normal skin, undergoes
      degradative changes leading to loss of functional elastic fibres. A potential
      strategy to counteract these degenerative changes entails topical application of
      a compound that may lead to regeneration of the elastic fibre network. In this
      study, we have evaluated the effects of a bi-metal, 0.1% copper-zinc malonate
      containing cream that has been shown to efface wrinkles in clinical trials. An
      effect on elastin biosynthesis and elastic tissue accumulation in skin biopsies
      was observed in 21 female patients with photoaged facial skin, as measured at
      baseline and at 6 weeks of treatment. Histopathological evaluation revealed
      evidence of elastic fibre regeneration, including those extending perpendicularly
      towards the dermo-epidermal junction within the papillary dermis. Elastin
      biosynthesis, measured by semi-quantitative immunofluorescence with an antibody
      recognizing only the newly synthesized, uncrosslinked tropoelastin molecules,
      suggested statistically significant enhancement of elastin biosynthesis by the bi
      metal compound when applied twice daily. Accumulation of elastic fibres was
      confirmed by assay of desmosine, an elastin-specific crosslink compound. These
      results suggest that the bi-metal, 0.1% copper-zinc malonate-containing cream has
      the propensity to increase elastin synthesis in human skin in vivo, and that
      regeneration of elastic fibres may contribute to wrinkle effacement in female
      patients with photoaged facial skin.

PMID- 19400835
TI  - Pathogen profile update: Fusarium oxysporum.
AB  - TAXONOMY: Kingdom Fungi; Phylum Ascomycota; Class Sordariomycetes; Order
      Hypocreales; Family Nectriaceae; genus Fusarium. HOST RANGE: Very broad at the
      species level. More than 120 different formae speciales have been identified
      based on specificity to host species belonging to a wide range of plant families.
      DISEASE SYMPTOMS: Initial symptoms of vascular wilt include vein clearing and
      leaf epinasty, followed by stunting, yellowing of the lower leaves, progressive
      wilting, defoliation and, finally, death of the plant. On fungal colonization,
      the vascular tissue turns brown, which is clearly visible in cross-sections of
      the stem. Some formae speciales are not primarily vascular pathogens, but cause
      foot and root rot or bulb rot. ECONOMIC IMPORTANCE: Can cause severe losses in
      many vegetables and flowers, field crops, such as cotton, and plantation crops,
      such as banana, date palm and oil palm. CONTROL: Use of resistant varieties is
      the only practical measure for controlling the disease in the field. In
      glasshouses, soil sterilization can be performed. USEFUL WEBSITES:
      http://www.broad.mit.edu/annotation/genome/fusarium_group/MultiHome.html;
      http://www.fgsc.net/Fusarium/fushome.htm; http://www.phi-base.org/query.php

PMID- 19400836
TI  - Pantoea ananatis: an unconventional plant pathogen.
AB  - Pantoea ananatis causes disease symptoms in a wide range of economically
      important agricultural crops and forest tree species worldwide. It is regarded as
      an emerging pathogen based on the increasing number of reports of diseases
      occurring on previously unrecorded hosts in different parts of the world. Its
      unconventional nature lies in the fact that, unlike the majority of plant
      pathogenic microbes, P. ananatis is capable of infecting humans and occurs in
      diverse ecological niches, such as part of a bacterial community contaminating
      aviation jet fuel tanks and contributing to growth promotion in potato and
      pepper. TAXONOMY: Bacteria; Gammaproteobacteria; family Enterobacteriaceae; genus
      Pantoea. MICROBIOLOGICAL PROPERTIES: Gram-negative; facultatively anaerobic; most
      strains are motile and produce a yellow pigment in culture; indole positive.
      BIOLOGY: Pantoea ananatis is a common epiphyte; it also occurs endophytically in
      hosts where it has been reported to cause disease symptoms and in hosts where no
      such symptoms have been described. Some strains are ice-nucleating, a feature
      which has been used as a biological control mechanism against some insect pests
      of agricultural crops and by the food industry. DISEASE SYMPTOMS: Pantoea
      ananatis infects both monocotyledonous and dicotyledonous plants. The symptoms
      are diverse depending on the host infected, and include leaf blotches and spots,
      die-back, and stalk, fruit and bulb rot. BIOLOGICAL CONTROL AGENT: Pantoea
      ananatis has both antifungal and antibacterial properties. These characteristics
      have the potential of being exploited by biological control specialists.

PMID- 19400837
TI  - Phospholipase C-mediated calcium signalling is required for fungal development
      and pathogenicity in Magnaporthe oryzae.
AB  - Calcium signalling has profound implications in the fungal infection of plants
      and animals, during which a series of physiological and morphological transitions
      are required. In this article, using a model fungal pathogen, Magnaporthe oryzae,
      we demonstrate that the regulation of the intracellular calcium concentration
      ([Ca(2+)](int)) is essential for fungal development and pathogenesis. Imaging of
      [Ca(2+)](int) showed that infection-specific morphogenesis is highly correlated
      with the spatiotemporal regulation of calcium flux. Deletion of the fungal
      phospholipase C gene (M. oryzae phospholipase C 1, MoPLC1) suppressed calcium
      flux, resulting in a fungus defective in developmental steps, including
      appressorium formation and pathogenicity. Surprisingly, the PLC-delta1 gene of
      mouse was able to functionally substitute for MoPLC1 by restoring the calcium
      flux, suggesting the evolutionary conservation of the phospholipase C-mediated
      regulation of calcium flux. Our results reveal that MoPLC1 is a conserved
      modulator of calcium flux that is essential for the regulation of key steps in
      fungal development and pathogenesis.

PMID- 19400838
TI  - Quantitative trait loci meta-analysis of Plum pox virus resistance in apricot
      (Prunus armeniaca L.): new insights on the organization and the identification of
      genomic resistance factors.
AB  - Plum pox virus (PPV) is responsible for sharka disease, one of the most
      detrimental stone fruit diseases affecting Prunus trees worldwide. Only a few
      apricot cultivars have been described as resistant, most originating from North
      American breeding programmes. Several PPV resistance quantitative trait loci
      (QTLs) have been mapped in various progenies, consistently highlighting the
      contribution to the resistance of the upper part of linkage group 1 (LG1).
      However, to date, no consensus has been reached on the precise number of QTLs
      linked to the resistance to PPV in apricot and P. davidiana or on their accurate
      position on the genetic linkage map. In the present study, the quantitative
      resistance of cultivar 'Harlayne' was analysed over five growth periods in a
      large F1 population. Four QTLs were identified, three mapping on LG1, explaining
      between 5% and 39% of the observed phenotypic variance. In an effort to further
      this analysis of PPV resistance in apricot, these results were merged in a single
      QTL meta-analysis with those of five other PPV resistance analyses available in
      the literature. Three consensus QTL regions were identified on LG1 and a putative
      fourth region on LG3. QTL meta-analysis also revealed the contribution of each
      resistant cultivar to metaQTLs, providing interesting comparative data on the
      resistance factors shared between the resistance sources used in the various
      studies. Finally, it was shown that one of the metaQTLs co-localizes with the
      eukaryotic translation initiation factor eIF4E, thus providing new hypotheses on
      the mechanisms of PPV resistance in apricot.

PMID- 19400839
TI  - Molecular cloning and characterization of the AVR-Pia locus from a Japanese field
      isolate of Magnaporthe oryzae.
AB  - In order to clone and analyse the avirulence gene AVR-Pia from Japanese field
      isolates of Magnaporthe oryzae, a mutant of the M. oryzae strain Ina168 was
      isolated. This mutant, which was named Ina168m95-1, gained virulence towards the
      rice cultivar Aichi-asahi, which contains the resistance gene Pia. A DNA fragment
      (named PM01) that was deleted in the mutant and that co-segregated with
      avirulence towards Aichi-asahi was isolated. Three cosmid clones that included
      the regions that flanked PM01 were isolated from a genomic DNA library. One of
      these clones (46F3) complemented the mutant phenotype, which indicated clearly
      that this clone contained the avirulence gene AVR-Pia. Clone 46F3 contained
      insertions of transposable elements. The 46F3 insert was divided into fragments I
      VI, and these were cloned individually into a hygromycin-resistant vector for the
      transformation of the mutant Ina168m95-1. An inoculation assay of the
      transformants revealed that fragment V (3.5 kb) contained AVR-Pia. By deletion
      analysis of fragment V, AVR-Pia was localized to an 1199-bp DNA fragment, which
      included a 255-bp open reading frame with weak homology to a bacterial cytochrome
      c-like protein. Restriction fragment length polymorphism analysis of this region
      revealed that this DNA sequence co-segregated with the AVR-Pia locus in a genetic
      map that was constructed using Chinese isolates.

PMID- 19400840
TI  - Microbe-associated molecular pattern (MAMP) signatures, synergy, size and charge:
      influences on perception or mobility and host defence responses.
AB  - Triggering of defences by microbes has mainly been investigated using single
      elicitors or microbe-associated molecular patterns (MAMPs), but MAMPs are
      released in planta as complex mixtures together with endogenous oligogalacturonan
      (OGA) elicitor. We investigated the early responses in Arabidopsis of calcium
      influx and oxidative burst induced by non-saturating concentrations of bacterial
      MAMPs, used singly and in combination: flagellin peptide (flg22), elongation
      factor peptide (elf18), peptidoglycan (PGN) and component muropeptides, lipo
      oligosaccharide (LOS) and core oligosaccharides. This revealed that some MAMPs
      have additive (e.g. flg22 with elf18) and even synergistic (flg22 and LOS)
      effects, whereas others mutually interfere (flg22 with OGA). OGA suppression of
      flg22-induced defences was not a result of the interference with the binding of
      flg22 to its receptor flagellin-sensitive 2 (FLS2). MAMPs induce different
      calcium influx signatures, but these are concentration dependent and unlikely to
      explain the differential induction of defence genes [pathogenesis-related gene 1
      (PR1), plant defensin gene 1.2 (PDF1.2) and phenylalanine ammonia lyase gene 1
      (PAL1)] by flg22, elf18 and OGA. The peptide MAMPs are potent elicitors at
      subnanomolar levels, whereas PGN and LOS at high concentrations induce low and
      late host responses. This difference might be a result of the restricted access
      by plant cell walls of MAMPs to their putative cellular receptors. flg22 is
      restricted by ionic effects, yet rapidly permeates a cell wall matrix, whereas
      LOS, which forms supramolecular aggregates, is severely constrained, presumably
      by molecular sieving. Thus, MAMPs can interact with each other, whether directly
      or indirectly, and with the host wall matrix. These phenomena, which have not
      been considered in detail previously, are likely to influence the speed,
      magnitude, versatility and composition of plant defences.

PMID- 19400841
TI  - Characterization of a putative endoxylanase in the migratory plant-parasitic
      nematode Radopholus similis.
AB  - Plant-parasitic nematodes have developed an arsenal of enzymes to degrade the
      rigid plant cell wall. In this article, we report the presence of a putative
      endoxylanase in the migratory endoparasitic nematode Radopholus similis. This
      enzyme is thought to facilitate the migration of the nematode, as it breaks down
      xylan, the major component of hemicellulose. The corresponding gene (Rs-xyl1) was
      cloned and the sequence revealed three small introns. Interestingly, the position
      of all three introns was conserved in a putative endoxylanase from Meloidogyne
      hapla, and the position of one intron was conserved in two endoxylanases from
      Meloidogyne incognita, which suggests a common ancestral gene. The spatial and
      temporal expression of the Rs-xyl1 gene was examined by in situ hybridization and
      semi-quantitative reverse transcriptase-polymerase chain reaction. The putative
      protein consists of a signal peptide, a catalytic domain and a carbohydrate
      binding module (CBM). The catalytic domain showed similarity to both glycosyl
      hydrolase family 5 (GHF5) and GHF30 enzymes. Using Hidden Markov Model profiles
      and phylogenetic analysis, we were able to show that Rs-XYL1 and its closest
      homologues are not members of GHF5, as suggested previously, but rather form a
      subclass within GHF30. Silencing the putative endoxylanase by double-stranded RNA
      targeting of the CBM region resulted in an average decrease in infection of 60%,
      indicating that the gene is important for the nematode to complete its life
      cycle.

PMID- 19400842
TI  - Development of taxon-specific sequence characterized amplified region (SCAR)
      markers based on actin sequences and DNA amplification fingerprinting (DAF): a
      case study in the Phoma exigua species complex.
AB  - Phoma exigua is considered to be an assemblage of at least nine varieties that
      are mainly distinguished on the basis of host specificity and pathogenicity.
      However, these varieties are also reported to be weak pathogens and secondary
      invaders on non-host tissue. In practice, it is difficult to distinguish P.
      exigua from its close relatives and to correctly identify isolates up to the
      variety level, because of their low genetic variation and high morphological
      similarity. Because of quarantine issues and phytosanitary measures, a robust DNA
      based tool is required for accurate and rapid identification of the separate taxa
      in this species complex. The present study therefore aims to develop such a tool
      based on unique nucleotide sequence identifiers. More than 60 strains of P.
      exigua and related species were compared in terms of partial actin gene
      sequences, or analysed using DNA amplification fingerprinting (DAF) with short,
      arbitrary, mini-hairpin primers. Fragments in the fingerprint unique to a single
      taxon were identified, purified and sequenced. Alignment of the sequence data and
      subsequent primer trials led to the identification of taxon-specific sequence
      characterized amplified regions (SCARs), and to a set of specific oligonucleotide
      combinations that can be used to identify these organisms in plant quarantine
      inspections.

PMID- 19400843
TI  - A severe symptom phenotype in tomato in Mali is caused by a reassortant between a
      novel recombinant begomovirus (Tomato yellow leaf curl Mali virus) and a
      betasatellite.
AB  - Tomato production in West Africa has been severely affected by begomovirus
      diseases, including yellow leaf curl and a severe symptom phenotype,
      characterized by extremely stunted and distorted growth and small deformed
      leaves. Here, a novel recombinant begomovirus from Mali, Tomato yellow leaf curl
      Mali virus (TYLCMLV), is described that, alone, causes tomato yellow leaf curl
      disease or, in combination with a betasatellite, causes the severe symptom
      phenotype. TYLCMLV is an Old World monopartite begomovirus with a hybrid genome
      composed of sequences from Tomato yellow leaf curl virus-Mild (TYLCV-Mld) and
      Hollyhock leaf crumple virus (HoLCrV). A TYLCMLV infectious clone induced leaf
      curl and yellowing in tomato, leaf curl, crumpling and yellowing in Nicotiana
      benthamiana and common bean, mild symptoms in N. glutinosa, and a symptomless
      infection in Datura stramonium. In a field-collected sample from a tomato plant
      showing the severe symptom phenotype in Mali, TYLCMLV was detected together with
      a betasatellite, identified as Cotton leaf curl Gezira betasatellite (CLCuGB).
      Tomato plants co-agroinoculated with TYLCMLV and CLCuGB developed severely
      stunted and distorted growth and small crumpled leaves. These symptoms were more
      severe than those induced by TYLCMLV alone, and were similar to the severe
      symptom phenotype observed in the field in Mali and in other West African
      countries. TYLCMLV and CLCuGB also induced more severe symptoms than TYLCMLV in
      the other solanaceous hosts, but not in common bean. The increased symptom
      severity was associated with hyperplasia of phloem-associated cells, but
      relatively little increase in TYLCMLV DNA levels. In surveys of tomato virus
      diseases in West Africa, TYLCMLV was commonly detected in plants with leaf curl
      and yellow leaf curl symptoms, whereas CLCuGB was infrequently detected and
      always in association with the severe symptom phenotype. Together, these results
      indicate that TYLCMLV causes tomato yellow leaf curl disease throughout West
      Africa, whereas TYLCMLV and CLCuGB represent a reassortant that causes the severe
      symptom phenotype in tomato.

PMID- 19400844
TI  - Candidate effector gene identification in the ascomycete fungal phytopathogen
      Venturia inaequalis by expressed sequence tag analysis.
AB  - The hemi-biotrophic fungus Venturia inaequalis infects members of the Maloideae,
      causing the economically important apple disease, scab. The plant-pathogen
      interaction of Malus and V. inaequalis follows the gene-for-gene model. cDNA
      libraries were constructed, and bioinformatic analysis of the resulting expressed
      sequence tags (ESTs) was used to characterize potential effector genes. Effectors
      are small proteins, secreted in planta, that are assumed to facilitate infection.
      Therefore, a cDNA library was constructed from a compatible interaction. To
      distinguish pathogen from plant sequences, the library was probed with genomic
      DNA from V. inaequalis to enrich for pathogen genes, and cDNA libraries were
      constructed from in vitro-grown material. A suppression subtractive hybridization
      library enriched for cellophane-induced genes was included, as growth on
      cellophane may mimic that in planta, with the differentiation of structures
      resembling those formed during plant colonization. Clustering of ESTs from the in
      planta and in vitro libraries indicated a fungal origin of the resulting non
      redundant sequence. A total of 937 ESTs was classified as putatively fungal,
      which could be assembled into 633 non-redundant sequences. Sixteen new candidate
      effector genes were identified from V. inaequalis based on features common to
      characterized effector genes from filamentous fungi, i.e. they encode a small,
      novel, cysteine-rich protein, with a putative signal peptide. Three of the 16
      candidates, in particular, conformed to most of the protein structural
      characteristics expected of fungal effectors and showed significant levels of
      transcriptional up-regulation during in planta growth. In addition to candidate
      effector genes, this collection of ESTs represents a valuable genomic resource
      for V. inaequalis.

PMID- 19400846
TI  - Expression and function of ryanodine receptors in rabbit penile corpus cavernosum
      smooth muscle cells.
AB  - This study aimed to investigate the expression and function of ryanodine
      receptors (RyRs) in rabbit penile corpus cavernosum smooth muscle (CCSM) cells.
      New Zealand white rabbit CCSM cells were cultured by primary tissue culture and
      identified by immunofluorescence technique. mRNA of three RyRs subunits in
      cultured CCSM cells was detected by reverse transcription polymerase chain
      reaction (RT-PCR). After excitation by noradrenaline, the concentration of Ca(2+)
      in CCSM cells was detected by laser scanning confocal microscopy. It was found
      that only the RyRs1 subunit is expressed in CCSM by RT-PCR. The CCSM cells were
      divided into two groups: Group A, CCSM cells + 10 micromol l(-1) noradrenaline
      and Group B, CCSM cells + 50 micromol l(-1) procaine 10 micromol l(-1)
      noradrenaline. Compared with the base level and the level after noradrenaline
      excitation, fluorescence intensity improved 44.10 +/- 6.01% in the test group A
      (n = 8) and 32.92 +/- 4.92% (n = 8) in the procaine control group B,
      respectively. There were statistically significant differences between group A
      and group B (P < 0.01). It is concluded that RyRs1 subunit is expressed in CCSM
      cells and may contribute to regulating the cytoplasmic Ca(2+) level.

PMID- 19400847
TI  - Sperm chromatin integrity in young men with no experiences of infertility and men
      from idiopathic infertility couples.
AB  - Damage to the genetic component of spermatozoa seems to play the main role in a
      majority of cases where current approaches fail to reveal the specific cause of
      male infertility. In this study, we compared semen quality in men assigned to two
      defined groups: men from couples with unexplained infertility - idiopathic
      infertility (A) and young men with no experiences of infertility (B). All samples
      were examined by standard ejaculate analysis and sperm chromatin structure assay
      (SCSA). Sperm chromatin damage was significantly higher in men from group A than
      in those from group B. Similar results were obtained by comparison of men from
      group A (all men were normozoospermic) with normozoospermic men from group B.
      According to these results, we can suppose that chromatin disorders may be the
      causal factor of subfertility or infertility in some of these men. No evidence
      for a strong association between chromatin disorders and standard parameters of
      ejaculates was found. We failed to confirm a relationship between smoking and
      sperm quality in men from any of the investigated groups. SCSA is a method that
      facilitates the identification of infertile men who otherwise show normal semen
      variables.

PMID- 19400848
TI  - Relationship between semen quality and seminal plasma components: alpha
      glucosidase, fructose and citrate in infertile men compared with a normospermic
      population of Tunisian men.
AB  - The aim of this study was to evaluate the correlation between the secretory
      function of the male accessory glands and sperm parameters in normospermic
      controls and infertile patients. One hundred and fifty-nine men were
      investigated: they were composed of two groups: normospermic (n = 37) and
      infertile (n = 122) men with altered sperm characteristics. These infertile men
      were divided into the following groups: asthenozoospermia (n = 38),
      teratozoospermia (n = 40) and asthenoteratozoospermia (n = 44). The patients
      underwent semen analysis and measurements of fructose, neutral alpha-glucosidase
      and citric acid. The level of fructose was significantly decreased in
      asthenozoospermic and increased in asthenoteratozoospermic men. It was
      significantly correlated with semen volume, sperm count, motility and morphology.
      The seminal alpha-glucosidase levels were significantly correlated with semen
      volume and pH and citric acid was significantly correlated with pH. Thus, alpha
      glucosidase and citric acid levels were associated with semen pH. The significant
      correlation between semen parameters, accessory glands and epididymal functions
      highlights the relationship between semen and normal genital tract function.

PMID- 19400849
TI  - Comparison of semen profile and frequency of chromosome aneuploidies in sperm
      nuclei of patients with varicocele before and after varicocelectomy.
AB  - Semen profile and meiotic segregation products are important for assessing
      aneuploidy risk and risk of resulting infertility. To determine the effect of
      varicocelectomy on semen profile and aneuploidy frequency, we investigated semen
      profile and aneuploidy frequency of selected chromosomes in patients with
      varicocele before and after varicocelectomy. Chromosomal aneuploidy for selected
      chromosomes was evaluated using chromosome-specific DNA fluorescence in situ
      hybridisation (FISH) probes. There was a significant difference in the level of
      normal sperm morphology before and after varicocelectomy (P > 0.007). There were
      no significant differences in aneuploidy frequency of chromosomes 1, 16, 17 and
      18 in sperm nuclei obtained from patients before varicocelectomy compared with 6
      7 months after varicocelectomy (P > 0.05), although FISH analysis with
      chromosomes 17 and 18 combination showed a higher aneuploidy frequency before
      varicocelectomy than after varicocelectomy (7.81 +/- 9.67 versus 4.03 +/- 1.46
      respectively). In conclusion, varicocele seems to affect the semen profile but
      minimally affects aneuploidy frequency. Varicocelectomy demonstrates a repairing
      effect on the semen profile and contributes to a slight decrease in aneuploidy
      frequency in some but not all chromosomes.

PMID- 19400850
TI  - Effects of indoor air purification by an air cleaning system (Koala technology)
      on semen parameters in male factor infertility: results of a pilot study.
AB  - A number of studies indicated a clear decline in semen quality in the past 30-50
      years and there is accumulating evidence that this decline might result from
      exposure to high levels of air pollution. To examine the impact of environment on
      male reproductive ability, we undertook for the first time a pilot study on semen
      quality of infertile men exposed to purification of indoor air. Ten subjects with
      a history of unexplained male infertility and poor semen quality were exposed for
      at least 1 year to a cleaning indoor air system (Koala technology). The key
      feature of this air purifier is the unique innovative multiple filtering system.
      The treatment of total purification of indoor air showed neither improvements in
      semen parameters nor variation in reproductive hormones (P = N.S.), but induced
      an evident increase (P < 0.03 and more) in seminal leucocytic concentrations.
      Within the limits due to the small sample of subjects recruited, the sole
      purification of indoor air does not seem enough to improve semen quality,
      although the increase in leucocytic concentrations could indicate an activation
      of the role of immunosurveillance in a purified indoor air environment.

PMID- 19400851
TI  - Safety and efficacy of vardenafil versus sertraline in the treatment of premature
      ejaculation: a randomised, prospective and crossover study.
AB  - We investigated safety and efficacy of vardenafil and sertraline in premature
      ejaculation (PE). Seventy-two men graded their primary PE on a scale of 0-8 (0 =
      almost never, 8 = almost always). Intravaginal ejaculatory latency time (IELT)
      was measured. Patients were included if they scored their PE as 4 or greater and
      their IELTs were less than 1.30 min. After 6 weeks of behavioural psychosexual
      therapy, 49 patients still had a PE of 4 or greater and an IELT less than 1.30
      min and they were randomised: 6 weeks vardenafil (10 mg) or sertraline (50 mg).
      After a wash-out phase for 1 week, medication was changed in a cross-over design.
      Initially, all 72 men with PE received behavioural therapy. Twenty-three men were
      satisfied with treatment and excluded. The remaining 49 men graded their PE as
      5.94 +/- 1.6 and IELT was 0.59 min and patients were randomised. Four men
      discontinued the study. Vardenafil improved PE grading: 2.7 +/- 2.1 (P < 0.01)
      and IELT increased to 5.01 +/- 3.69 (P < 0.001). PE grading improved 1.92 +/-
      1.32, (P < 0.01) and IELT 3.12 +/- 1.89 (P < 0.001) with sertraline. It is
      concluded that vardenafil and sertraline are useful agents in the pharmacological
      treatment of PE.

PMID- 19400852
TI  - Effect of HO-1 cDNA-liposome complex transfer on erectile signalling of aged
      rats.
AB  - This work aimed to assess the efficacy of haeme oxygenase-1 (HO-1) cDNA-liposome
      complex transfer as a mediator of erectile signalling in aged rats. One hundred
      and fifty aged white albino rats were equally divided into five groups: controls,
      rats receiving lipofectamine, rats receiving intracorporeal HO-1 cDNA-lipsome
      complex, rats receiving HO-1 cDNA-liposome complex plus nitric oxide synthase
      (NOS) inhibitor, and rats receiving HO-1 cDNA-liposome complex plus HO inhibitor.
      Six rats were killed from each group after 12, 24 and 48 h, and after1 and 2
      weeks. In dissected cavernous tissues, the following were assessed: HO-1 gene
      expression, Western blot for HO-1, HO enzyme activity, cGMP and histopathology.
      The results showed that HO-1 cDNA-liposome complex transfer led to a significant
      increase in cavernous tissue HO-1 protein, HO-1 gene expression, HO enzyme
      activity and cGMP up to 1 week. NOS inhibition exhibited no effect on HO-1 gene
      enhancement of cavernous tissue HO enzyme activity or cGMP, whereas inhibition of
      HO significantly decreased these parameters. Histopathology of cavernous tissue
      demonstrated a significant dilatation of helicine arteries in HO-1 cDNA-liposome
      complex treated group after 48 h compared with the controls. It is concluded that
      HO-1 cDNA-liposome complex transfer augments cavernous tissue cGMP with
      subsequent sinusoidal relaxation.

PMID- 19400853
TI  - Protein tyrosine phosphorylation under capacitating conditions in porcine fresh
      spermatozoa and sperm cryopreserved with and without alpha tocopherol.
AB  - The aim of this study was to evaluate the capacitation behaviour of fresh and
      alpha-tocopherol frozen spermatozoa. Spermatozoa frozen with or without alpha
      tocopherol and fresh semen were incubated under capacitating conditions. Aliquots
      were collected at 0, 15, 30, 45, 60, 90, 120 and 180 min of incubation time.
      Parameters of semen quality were evaluated by optical microscopy and capacitation
      was determined by the epifluorescence chlortetracycline technique. Protein
      tyrosine phosphorylation was examined by Western immunoblotting. Motility,
      viability and intact spermatozoa were higher (P < 0.05) in fresh semen compared
      with frozen samples. These parameters significantly decreased, in every
      treatment, throughout the incubation time. Fresh semen showed a progressive
      increase in capacitated spermatozoa, reaching 25 +/- 3% at 180 min. Cryopreserved
      semen had a fast increase at the beginning of incubation time (28 +/- 5% at 45
      min and 28 +/- 3% at 30 min for samples with or without alpha-tocopherol,
      respectively). The amount of an MW 32 kDa tyrosine-phosphorilated protein,
      associated with capacitation, increased throughout incubation for fresh semen and
      spermatozoa cryopreserved with alpha-tocopherol. The supplementation with alpha
      tocopherol preserved sperm plasma membrane, reflected not only in the acrosome
      integrity but also in a greater efficiency of energy production.

PMID- 19400854
TI  - Sexual functions of men with obstructive sleep apnoea syndrome and hypogonadism
      may improve upon testosterone administration: a pilot study.
AB  - This study examined 72 patients with obstructive sleep apnoea syndrome (OSAS),
      confirmed by polysomnography. Thirty-two patients were suffering from erectile
      dysfunction (ED) assessed by IIEF-5 questionnaires and confirmed by nocturnal
      penile tumescence examination. Their testosterone levels were measured. Eight
      patients had normal testosterone levels and were treated with a PDE-5 inhibitor
      (vardenafil) only; after 6 months of treatment, 6 of these patients (75%) showed
      significant improvement in erectile function. The remaining 24 patients with
      OSAS, ED and hypogonadism (total testosterone <12 nmol l(-1)), were divided into
      two groups based on the indication for continuous positive airway pressure (CPAP)
      therapy: five patients received CPAP therapy (group 1) and 19 patients did not
      (group 2). The patients of group 2 received only a PDE-5 inhibitor (vardenafil 20
      mg) for ED; and eight patients (42%) showed an improvement after 3 months of
      treatment. The five patients receiving CPAP therapy were treated with a
      combination of parenteral testosterone undecanoate and a PDE-5 inhibitor
      (vardenafil) and all had normal erectile function after 3 months of therapy. The
      results suggest positive effects of addition of testosterone to treatment with
      PDE-5 inhibitors in hypogonadal men with OSAS, which should be confirmed in
      larger controlled studies.

PMID- 19400855
TI  - Protective effect of fallopian tubal fluid against activated leucocyte-induced
      sperm DNA fragmentation: preliminary results.
AB  - The integrity of the paternal genome is of paramount importance in the initiation
      and maintenance of a viable pregnancy. Oxygen radicals (ROS) have been identified
      as one of the main factors responsible for the induction of sperm DNA damage.
      Spermatozoa are mainly protected against ROS-induced damage by seminal plasma.
      However, this protective effect disappears once spermatozoa enter the female
      genital tract. The fallopian tube mucosa may play a protective role against ROS
      induced sperm damage. The main objective of this study was to determine whether
      human tubal explants and tubal fluid exert a protective effect on ROS-induced
      sperm DNA damage. Spermatozoa were exposed to tubal explants and/or tubal fluid
      in the presence of phorbol myristate acetate (PMA)-activated polymorphonuclear
      leucocytes or control medium and sperm DNA fragmentation was measured using the
      TdT-mediated dUTP-biotin nick end labelling (TUNEL) test. Exposure of human
      spermatozoa to PMA-activated leucocytes resulted in a 2-fold increase in sperm
      DNA fragmentation. Co-incubation of spermatozoa with tubal explants did not
      reduce this damage. However, pre-incubation of spermatozoa with tubal fluid
      resulted in a statistically significant reduction in sperm DNA fragmentation
      levels, comparable to those observed in control. In conclusion, tubal fluid
      appears to protect against activated leucocyte-induced sperm DNA fragmentation,
      thus preserving the integrity of the paternal genome.

PMID- 19400856
TI  - Partial priapism secondary to tamsulosin: a case report and review of the
      literature.
AB  - Partial priapism is also called partial segmental thrombosis of the corpus
      cavernosum. It is a rare pathology, and its aetiology, physiopathology and
      treatment are still not completely understood. To our knowledge, partial priapism
      due to alpha blockers has not been reported previously in the literature. In this
      study, a successfully treated case of partial priapism occurring after the usage
      of alpha blocker is presented and discussed in light of the related literature.

PMID- 19400858
TI  - Host-microbe relations.

PMID- 19400859
TI  - Cooperation and conflict in host-microbe relations.
AB  - Hosts and microbes associate in a variety of relations along a continuum ranging
      from symbiotic to pathogenic. Defence mechanisms have been evolutionarily
      selected in both hosts and microbes to protect the organism's integrity. Such
      defences have to be utilized with caution. They must be adapted to the tasks at
      hand; otherwise any symbiotic relation would be impossible. To explain this
      cautionary use of defences we need to understand how life on Earth evolved into
      cooperative and competing entities at various levels of organization. The purpose
      of this article is to review theory and selected mechanisms relating to the
      evolution and development of host-microbe interactions, with special emphasis on
      host responses. The rationale is that without theory, extrapolations from
      misleading observations can dominate and distort, for a significant time, the
      course of a scientific field. The argument is set forth that social evolution
      theory provides a conceptual framework for addressing questions relating to
      interaction between hosts and microbes. The article is a partial summary of
      arguments presented in my book Defending life - the nature of host-parasite
      relations.

PMID- 19400860
TI  - Innate recognition of intracellular pathogens: detection and activation of the
      first line of defense.
AB  - The innate immune system constitutes the first line of defense against infections
      and is also important for initiating the development of an adaptive immune
      response. The innate immune system recognizes microbial infection through
      germline-encoded pattern recognition receptors, which are responsible for
      decoding the microbial fingerprint and activating an appropriate response against
      the invading pathogen. In this review, we present and discuss current knowledge
      on how the innate immune system recognizes intracellular pathogens, activates
      intracellular signaling, induces gene expression, and orchestrates the
      microbicidal response against pathogens with a habitat within host cells.

PMID- 19400861
TI  - Co-ordinating innate and adaptive immunity to viral infection: mobility is the
      key.
AB  - The host counters a viral infection through a complex response made up of
      components belonging to both the innate and the adaptive immune system. In this
      report, we review the mechanisms underlying this response, how it is induced and
      how it is co-ordinated. As cell-cell communication represents the very essence of
      immune system physiology, a key to a rapid, efficient and optimally regulated
      immune response is the ability of the involved cells to rapidly shift between a
      stationary and a mobile state, combined with stringent regulation of cell
      migration during the mobile state. Through the co-ordinated recruitment of
      different cell types intended to work in concert, cellular co-operation is
      optimized particularly under conditions that may involve rare cells.
      Consequently, a major focus is placed on presenting an overview of the co
      operative events and the associated cell migration, which is essential in
      mounting an efficient host response and co-ordinating innate and adaptive
      immunity during a primary viral infection.

PMID- 19400862
TI  - Virus-specific CD8 T cells: activation, differentiation and memory formation.
AB  - CD8 T cells are pivotal for the control of many intracellular pathogens, and
      besides their role in immediate control of infections, CD8 T cells have the
      capacity to differentiate into long-lived antigen-independent memory CD8 T cells,
      at least in situations of acute and resolved infections. The population of memory
      cells is heterogeneous with respect to their phenotype, their anatomical
      localization and their functional capacities in order to afford optimal
      protection against secondary infections. In the past years, it has become clear
      that multiple in vivo parameters are involved in shaping the composition of the
      memory CD8 T cell population, including antigen load, duration and strength of
      CD8 T cell stimulation, the level of inflammation, availability of CD4 T cell
      help and CD8 T cell precursor frequencies. With respect to the timing when CD8 T
      cells are committed to become memory cells, several models have been proposed. In
      contrast to acute, resolved infection, the continued in vivo exposure to high
      levels of antigen during persistent chronic viral infection precludes the
      development of long-lived antigen-independent memory CD8 T cells and might even
      result in severe dysfunction of virus-specific CD8 T cells.

PMID- 19400863
TI  - Tumour virology--history, status and future challenges.
AB  - Viruses enter host cells in order to complete their life cycles and have evolved
      to exploit host cell structures, regulatory factors and mechanisms. The virus and
      host cell interactions have consequences at multiple levels, spanning from
      evolution through disease to models and tools for scientific discovery and
      treatment. Virus-induced human cancers arise after a long duration of time and
      are monoclonal or oligoclonal in origin. Cancer is therefore a side effect rather
      than an essential part of viral infections in humans. Still, 15-20% of all human
      cancers are caused by viruses. A review of tumour virology shows its close
      integration in cancer research. Viral tools and experimental models have been
      indispensible for the progress of molecular biology. In particular, retroviruses
      and DNA tumour viruses have played major roles in our present understanding of
      the molecular biology of both viruses and the host. Recently, additional complex
      relationships due to virus and host co-evolution have appeared and may lead to a
      further understanding of the overall regulation of gene expression programmes in
      cancer.

PMID- 19400865
TI  - Dendritic cells in cytomegalovirus infection: viral evasion and host
      countermeasures.
AB  - Human cytomegalovirus (HCMV) is a beta-herpesvirus that infects the majority of
      the population during early childhood and thereafter establishes life-long
      latency. Primary infection as well as spontaneous reactivation usually remains
      asymptomatic in healthy hosts but can, in the context of systemic
      immunosuppression, result in substantial morbidity and mortality. HCMV
      counteracts the host immune response by interfering with the recognition of
      infected cells. A growing body of literature has also suggested that the virus
      evades the immune system by paralyzing the initiators of antiviral immune
      responses--the dendritic cells (DCs). In the current review, we discuss the
      effects of CMV (HCMV and murine CMV) on various DC subsets and the ensuing innate
      and adaptive immune responses. The impact of HCMV on DCs has mainly been
      investigated using monocyte-derived DCs, which are rendered functionally impaired
      by infection. In mouse models, DCs are targets of viral evasion as well, but the
      complex cross-talk between DCs and natural killer cells has, however,
      demonstrated an instrumental role for DCs in the control and clearance of viral
      infection. Fewer studies address the role of peripheral blood DC subsets,
      plasmacytoid DCs and CD11c+ myeloid DCs in the response against HCMV. These DCs,
      rather than being paralyzed by HCMV, are largely resistant to infection, mount a
      vigorous first-line defense and induce T-cell responses to the virus. This
      possibly provides a partial explanation for an intriguing conundrum: the highly
      efficient control of viral infection and reactivation in immunocompetent hosts in
      spite of multi-layered viral evasion mechanisms.

PMID- 19400866
TI  - The hepatitis C virus enigma.
AB  - Hepatitis C virus (HCV) has a high propensity to establish chronic infection with
      end-stage liver disease. The high turnover of virus particles and high
      transcription error rates due to lack of proof-reading function of the viral
      polymerase imply that HCV exists as quasispecies, thus enabling the virus to
      evade the host immune response. Clearance of the virus is characterized by a
      multispecific, vigorous and persistent T-cell response, whereas T-cell responses
      are weak, narrow and transient in patients who develop chronic infection. At
      present, standard treatment is a combination of pegylated interferon-alpha and
      ribavirin, with a sustained viral response rate of 40-80%, depending on genotype.
      The mechanisms for the observed synergistic effects of the two drugs are still
      not known in detail, but in addition to direct antiviral mechanisms, the
      immunomodulatory effects of both drugs seem to be important, with a shift from
      Th2- to Th1-cytokine profiles in successfully treated patients. This article
      describes virus-host relations in the natural course of HCV infection and during
      treatment.

PMID- 19400867
TI  - Interaction of Mycobacterium tuberculosis with the host: consequences for vaccine
      development.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains a
      major worldwide health problem that causes more than 2 million deaths annually.
      In addition, an estimated 2 billion people are latently infected with M.
      tuberculosis. The bacterium is one of the oldest human pathogens and has evolved
      complex strategies for survival. Therefore, to be successful in the high endemic
      regions, any future TB vaccine strategy will have to be tailored in accordance
      with the resulting complexity of the TB infection and anti-mycobacterial immune
      response. In this review, we will discuss what is presently known about the
      interaction of M. tuberculosis with the immune system, and how this knowledge is
      used in new and more advanced vaccine strategies.

PMID- 19400864
TI  - HIV and SIV infection: the role of cellular restriction and immune responses in
      viral replication and pathogenesis.
AB  - The human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV)
      have a long biological history. Both viruses evolved from Africa and remnants of
      them can be found in the 'fossil record' of several species in which they are not
      endemic. SIV remains endemic in several species of monkeys in Africa where it
      does not cause immune deficiency. HIV and SIV actively replicate within humans
      and Asian non-human primates, despite cellular and genetic viral restriction
      factors and genes, and at times robust innate and adaptive immune responses.
      While Lentiviruses are considered 'slow viruses' it is clear in humans and
      susceptible Asian monkeys that virus production is rapid and highly active. This
      results in a massive loss of CD4+ memory effector T cells early after infection
      and a continued race between viral evolution, cytotoxic lymphocytes, and failed
      neutralizing antibody responses. Concurrently, HIV and SIV can infect
      monocyte/macrophage populations in blood and more importantly in tissues,
      including the central nervous system, where the virus can remain sequestered and
      not cleared by anti-retroviral therapy, and hide for years. This review will
      discuss species and cellular barriers to infection, and the role of innate and
      acquired immunity with infection and pathogenesis of HIV and SIV in select
      species.

PMID- 19400869
TI  - Startle epilepsy associated with gait-induced seizures: Pathomechanism analysis
      using EEG, MEG, and PET studies.
AB  - We describe herein a girl who has had startle-induced seizures since she was 3
      years old. These seizures were refractory to antiepileptic medications and
      worsened when the patient was 9 years old, following termination of phenytoin
      administration because of adverse effects. During this period she could walk only
      a few steps with support, and sudden drop attacks inevitably occurred. Interictal
      electroencephalography (EEG) revealed abundant spike-wave activity at the
      centroparietal midline areas, and ictal EEG of poststartle and gait-induced
      seizures revealed initial voltage attenuation followed by recruitment of vertex
      activity, which preceded a tonic or myoclonic-atonic phase. Magnetic resonance
      imaging (MRI) results were unremarkable, but magnetoencephalography (MEG) and
      positron emission tomography (PET) suggested the presence of an extensive
      epileptogenic zone in the bilateral pericentral gyri, and the bilateral
      paracentral and left precuneus lobules, including the primary motor,
      supplementary motor, and supplementary sensory areas. The pathophysiologic
      significance of these structures is discussed.

PMID- 19400870
TI  - Susceptibility weighted imaging in the diagnostic evaluation of patients with
      intractable epilepsy.
AB  - AIM: Dedicated magnetic resonance imaging (MRI) protocol can diagnose
      epileptogenic abnormalities in patients with intractable epilepsy. However, it is
      not sufficiently sensitive to detect small calcified lesions that may result from
      infections, tumors, or vascular malformations. This study aims to study the
      impact of the addition of T2*gradient echo/susceptibility weighted imaging
      (T2*GRE/SWI) sequence to a dedicated MRI protocol. METHOD: One hundred thirty
      seven patients with intractable epilepsy underwent MRI using conventional
      epilepsy protocol with addition of T2*GRE/SWI sequence. Comparison of the images
      with and without these sequences was done for detection of calcified
      abnormalities/vascular abnormalities. In patients with calcified lesions, MRI
      findings were correlated either with histopathology or computerized tomography
      (CT) to confirm the presence of calcification. RESULTS: In 16 patients the
      sequence gave additional information compared to conventional imaging protocol.
      The sequence helped in better characterization of lesions in all patients. In
      three patients it helped in detecting the lesion and in another three it appeared
      useful as it best characterized the lesions. Additional lesions were detected in
      two patients with old calcified granulomas. Important additional information was
      supplied in four patients, whereas in the remaining patients lesion conspicuity
      was increased. CONCLUSION: T2*GRE/SWI sequence should form part of routine
      epilepsy protocol as it increases sensitivity by detecting occult calcified
      lesions or vascular malformations that may be responsible for the patient's
      seizures. This is especially important in patients from developing countries who
      have post-infective calcified lesions responsible for seizures and who undergo
      only MRI as the imaging modality for intractable seizures.

PMID- 19400868
TI  - Communication between Toxoplasma gondii and its host: impact on parasite growth,
      development, immune evasion, and virulence.
AB  - Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect
      most warm-blooded animals and cause severe and life-threatening disease in
      developing fetuses and in immune-compromised patients. Although Toxoplasma was
      discovered over 100 years ago, we are only now beginning to appreciate the
      importance of the role that parasite modulation of its host has on parasite
      growth, bradyzoite development, immune evasion, and virulence. The goal of this
      review is to highlight these findings, to develop an integrated model for
      communication between Toxoplasma and its host, and to discuss new questions that
      arise out of these studies.

PMID- 19400872
TI  - The use of radiosurgery for the treatment of mesial temporal lobe epilepsy and
      long-term results.
AB  - PURPOSE: To determine the efficacy of gamma knife radiosurgery in the treatment
      of mesial temporal lobe epilepsy due to mesial temporal sclerosis. METHODS:
      Between November 1995 and May 1999, 14 patients underwent radiosurgical
      entorhinoamygdalohippocampectomy with a marginal dose of 18, 20, or 25 Gy to the
      50% isodose following a standard preoperative epilepsy evaluation. RESULTS: One
      patient was classified as Engel Class Ib, three were Engel Class IIc, one was
      Engel Class IIIa, and two were Engel Class IVb in a subgroup of seven patients
      who were unoperated 2 years prior to the last visit and at least 8 years after
      irradiation (average 116 months). The insufficient effect of irradiation led us
      to perform epilepsy surgery on another seven patients an average of 63.5 months
      after radiosurgery. The average follow-up period was 43.5 months after the
      operation. Four patients are seizure-free; one is Engel Class IIb and one is
      Engel Class IId. One patient cannot be classified due to the short period of
      follow-up. The frequency of seizures tended to rise after irradiation in some
      patients. Collateral edema was observed in nine patients, which started earlier
      and was more frequent in those irradiated with higher doses. It had a marked
      expansive character in three cases and clinical signs of intracranial
      hypertension were present in three cases. We found partial upper lateral quadrant
      anopia as a permanent side effect in two patients. Repeated psychotic episodes
      (two patients) and status epilepticus (two patients) were also seen after
      treatment. No significant memory changes occurred in the group as a whole.
      DISCUSSION: Radiosurgery with 25, 20, or 18-Gy marginal dose levels did not lead
      to seizure control in our patient series, although subsequent epilepsy surgery
      could stop seizures. Higher doses were associated with the risk of brain edema,
      intracranial hypertension, and a temporary increase in seizure frequency.

PMID- 19400871
TI  - High frequency oscillations (80-500 Hz) in the preictal period in patients with
      focal seizures.
AB  - PURPOSE: Intracranial depth macroelectrode recordings from patients with focal
      seizures demonstrate interictal and ictal high frequency oscillations (HFOs, 80
      500 Hz). These HFOs are more frequent in the seizure-onset zone (SOZ) and
      reported to be linked to seizure genesis. We evaluated whether HFO activity
      changes in a systematic way during the preictal period. METHODS: Fifteen minutes
      of preictal intracranial electroencephalography (EEG) recordings were evaluated
      in seven consecutive patients with well-defined SOZ. EEG was filtered at 500 Hz
      and sampled at 2,000 Hz. Ripples (80-250 Hz) and fast ripples (250-500 Hz) were
      visually marked, and spectral analysis was performed in seizure-onset as well as
      nonseizure-onset channels. Linear regressions fitted to the power trends
      corresponding to intervals of 1, 5, and 15 min before the seizure onset was
      calculated. RESULTS: Total rates of HFOs were significantly higher in the SOZ
      than outside. Preictal increases and decreases in HFO rates and band power could
      be detected in all patients, and they were not limited to the SOZs. These
      measures were very variable, and no systematic trends were observed when
      comparing patients or seizures in the same patient. DISCUSSION: High frequencies
      in the range of 80-500 Hz are present during the preictal period and are more
      prominent in the SOZ. They do not change in a systematic way before seizure onset
      for the horizons we tested. The 80-500 Hz band may be used for the localization
      of seizure-onset areas but may be more difficult to use for seizure prediction
      purposes.

PMID- 19400873
TI  - A longitudinal study of surgical outcome and its determinants following posterior
      cortex epilepsy surgery.
AB  - PURPOSE: To investigate the longitudinal seizure outcome and identify potential
      prognostic indicators following posterior cortex epilepsy (PCE) surgery. METHODS:
      We reviewed patients who underwent a parietal, occipital, or parietooccipital
      resections between 1994 and 2006, using survival analysis and multivariate
      regression with Cox proportional hazard modeling. A favorable outcome was defined
      as Engel Class I at last follow-up. RESULTS: Fifty-seven patients were identified
      with a mean follow-up of 3.3 years (range 1-12 years). The estimated chance of
      seizure freedom (SF) was 73.1% at 6 postoperative months, 68.5% at 1 year, 65.8%
      at between 2 and 5 years, and 54.8% at 6 years and beyond. Most recurrences (75%)
      occurred within the first 6 postoperative months. Parietal resections had a worse
      outcome than occipital or parietooccipital resections (52% SF vs. 89% and 93%,
      respectively, at 5 years). Independent predictors of recurrence included an
      epilepsy etiology other than tumor or dysplasia [risk ratio (RR) 2.29], limiting
      resection to a lesionectomy (RR 2.10), having ipsilateral temporal spiking on
      preoperative scalp electroencephalography (EEG) (RR 2.06), or any ipsilateral
      spiking on postoperative EEG (RR 2.70) (Log likelihood-ratio test p < 0.0001).
      Only 40-50% of patients with a poor outcome predictor were SF at 5 postoperative
      years as opposed to about 80% otherwise. In surgical failures, recurrent seizure
      frequency was related directly to baseline seizure frequency and to the presence
      of ipsilateral spiking on postoperative EEG. DISCUSSION: These data highlight
      favorable long-term outcomes following PCE surgery. Limited surgical resection
      and diffuse baseline epileptogenicity may be important predictors of seizure
      recurrence.

PMID- 19400875
TI  - Asymmetric seizure termination in primary and secondary generalized tonic-clonic
      seizures.
AB  - PURPOSE: In temporal lobe epilepsies an asymmetric termination (AST) of the
      clonic phase of secondary generalized tonic-clonic seizures (sGTCS) reliably
      lateralizes the side of seizure onset. The last clonic activity occurs
      ipsilateral to the side of the seizure onset zone. We compared the prevalence and
      lateralizing value of AST in sGTCS of frontal and temporal lobe origin as well as
      in primary generalized tonic-clonic seizures (pGTCS). METHODS: We analyzed 177
      seizures in 84 consecutive patients. Forty-one patients had temporal lobe
      epilepsy (TLE), 24 frontal lobe epilepsy (FLE), and 19 had nonfocal (primary)
      generalized epilepsies (GE). All patients underwent intensive video-EEG
      (electroencephalography) monitoring, high-resolution magnetic resonance imaging
      (MRI), neuropsychological testing, and single photon emission computed
      tomography/positron emission tomography (SPECT/PET) when feasible. Two
      investigators blinded for diagnosis, EEG, and imaging data assessed frequency and
      side of the last clonic jerk. RESULTS: AST occurred in 63% of patients with TLE
      (47% of seizures), in 71% with FLE (60% of seizures), and in 42% with GE (21% of
      seizures). These results were not significant for patients, but significant for
      seizures in TLE versus GE and in FLE versus GE (p < 0.001). The positive
      predictive value (PPV) for the side of seizure onset was 74% (p = 0.003) in TLE
      and 75% (p = 0.008) in FLE. DISCUSSION: AST in sGTCS lateralizes the side of
      seizure onset in TLE and in FLE to the ipsilateral hemisphere with a high PPV.
      However, AST was also observed in GE. Therefore, asymmetric clinical signs should
      not inevitably lead to the assumption of focal epilepsy syndromes.

PMID- 19400874
TI  - Cardiac function and antiepileptic drug treatment in the elderly: a comparison
      between lamotrigine and sustained-release carbamazepine.
AB  - PURPOSE: To investigate the comparative effects of carbamazepine (CBZ) and
      lamotrigine (LTG) on electrocardiography (ECG) parameters in elderly patients
      with newly diagnosed epilepsy. METHODS: The study was conducted in the Norwegian
      subcohort (n = 108) of an international randomized double-blind 40-week trial,
      which compared the efficacy and tolerability of LTG and sustained-release CBZ in
      patients aged 65 and older with newly diagnosed epilepsy. Target maintenance
      doses were 400 mg/day for CBZ and 100 mg/day for LTG, with adjustments based on
      clinical response. Patients with significant unpaced atrioventricular (AV)
      conduction defect were excluded. Resting 12-lead ECG recordings were made under
      standardized conditions at pretreatment (baseline) and at the 40-week study visit
      (treatment visit). Changes in QRS interval (primary endpoint), heart rate (HR),
      PQ, and QTc (HR-corrected QT) intervals were assessed and compared between
      groups. RESULTS: Of the 108 patients randomized, 33 discontinued prematurely
      because of adverse events (n = 24, none of which was cardiac) or other reasons (n
      = 9), and 15 were nonevaluable due to incomplete ECG data. None of the assessed
      ECG parameters differed significantly between groups at baseline. No significant
      ECG changes were recorded between baseline and treatment visit for QRS duration
      and QTc intervals, whereas HR fell and PQ intervals increased slightly on both
      treatments. However, there were no differences between groups in changes from
      baseline to treatment visit. There were no significant relationships between
      individual ECG changes and serum drug concentrations, except for QTc intervals,
      which decreased slightly with increasing CBZ concentrations. The proportion of
      patients with ECG parameters outside the normal range at treatment visit was
      similar to that recorded at baseline. DISCUSSION: Clinically significant ECG
      changes are not common during treatment with CBZ or LTG in elderly patients with
      no preexisting significant AV conduction defects.

PMID- 19400876
TI  - Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32.
AB  - PURPOSE: The restricted genetic diversity and homogeneous molecular basis of
      Mendelian disorders in isolated founder populations have rarely been explored in
      epilepsy research. Our long-term goal is to explore the genetic basis of
      epilepsies in one such population, the Gypsies. The aim of this report is the
      clinical and genetic characterization of a Gypsy family with a partial epilepsy
      syndrome. METHODS: Clinical information was collected using semistructured
      interviews with affected subjects and informants. At least one interictal
      electroencephalography (EEG) recording was performed for each patient and
      previous data obtained from records. Neuroimaging included structural magnetic
      resonance imaging (MRI). Linkage and haplotype analysis was performed using the
      Illumina IVb Linkage Panel, supplemented with highly informative microsatellites
      in linked regions and Affymetrix SNP 5.0 array data. RESULTS: We observed an
      early-onset partial epilepsy syndrome with seizure semiology strongly suggestive
      of temporal lobe epilepsy (TLE), with mild intellectual deficit co-occurring in a
      large proportion of the patients. Psychiatric morbidity was common in the
      extended pedigree but did not cosegregate with epilepsy. Linkage analysis
      definitively excluded previously reported loci, and identified a novel locus on
      5q31.3-q32 with an logarithm of the odds (LOD) score of 3 corresponding to the
      expected maximum in this family. DISCUSSION: The syndrome can be classified as
      familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild
      intellectual deficit. The linked 5q region does not contain any ion channel
      encoding genes and is thus likely to contribute new knowledge about epilepsy
      pathogenesis. Identification of the mutation in this family and in additional
      patients will define the full phenotypic spectrum.

PMID- 19400877
TI  - Are personality traits of juvenile myoclonic epilepsy related to frontal lobe
      dysfunctions? A proton MRS study.
AB  - PURPOSE: Personality traits characterized by emotional instability and
      immaturity, unsteadiness, lack of discipline, hedonism, frequent and rapid mood
      changes, and indifference toward one's disease have been associated with patients
      who have juvenile myoclonic epilepsy (JME). Literature data demonstrate worse
      seizure control and more psychosocial dysfunctions among patients with JME who
      have those traits. In this controlled study we performed a correlation analysis
      of psychiatric scores with magnetic resonance spectroscopy (MRS) values across
      JME patients, aiming to verify the existence of a possible relation between
      frontal lobe dysfunction and the prevalence of personality disorders (PDs) in
      JME. METHODS: Sixteen JME patients with cluster B PDs, 41 JME patients without
      any psychiatric disorder, and 30 healthy controls were submitted to a psychiatric
      evaluation and to a quantitative multivoxel MRS of thalamus; insula; cingulate
      gyrus; striatum; and frontal, parietal, and occipital lobes. Groups were
      homogeneous according to age, gender, and manual dominance. Psychiatric
      evaluation was performed through the Scheduled Clinical Interview for DSM-IV,
      Axis I and II (SCID I and II, respectively). RESULTS: A significant reduction of
      N-acetyl-aspartate over creatinine (NAA/Cr) ratio was observed mainly in the left
      frontal lobe in the JME and PD group. In addition, a significant increase in the
      glutamate-glutamine over creatinine GLX/Cr ratio was also observed in this
      referred region in the same group. DISCUSSION: These data support the hypothesis
      that PDs in JME could represent neuronal dysfunction and possibly a more severe
      form of this epileptic syndrome.

PMID- 19400878
TI  - SCN1A duplications and deletions detected in Dravet syndrome: implications for
      molecular diagnosis.
AB  - OBJECTIVE: We aimed to determine the type, frequency, and size of
      microchromosomal copy number variations (CNVs) affecting the neuronal sodium
      channel alpha 1 subunit gene (SCN1A) in Dravet syndrome (DS), other epileptic
      encephalopathies, and generalized epilepsy with febrile seizures plus (GEFS+).
      METHODS: Multiplex ligation-dependent probe amplification (MLPA) was applied to
      detect SCN1A CNVs among 289 cases (126 DS, 97 GEFS+, and 66 with other
      phenotypes). CNVs extending beyond SCN1A were further characterized by
      comparative genome hybridization (array CGH). RESULTS: Novel SCN1A CNVs were
      found in 12.5% of DS patients where sequence-based mutations had been excluded.
      We identified the first partial SCN1A duplications in two siblings with typical
      DS and in a patient with early-onset symptomatic generalized epilepsy. In
      addition, a patient with DS had a partial SCN1A amplification of 5-6 copies. The
      remaining CNVs abnormalities were four partial and nine whole SCN1A deletions
      involving contiguous genes. Two CNVs (a partial SCN1A deletion and a duplication)
      were inherited from a parent, in whom there was mosaicism. Array CGH showed
      intragenic deletions of 90 kb and larger, with the largest of 9.3 Mb deleting 49
      contiguous genes and extending beyond SCN1A. DISCUSSION: Duplication and
      amplification involving SCN1A are now added to molecular mechanisms of DS
      patients. Our findings showed that 12.5% of DS patients who are mutation negative
      have MLPA-detected SCN1A CNVs with an overall frequency of about 2-3%. MLPA is
      the established second-line testing strategy to reliably detect all CNVs of SCN1A
      from the megabase range down to one exon. Large CNVs extending outside SCN1A and
      involving contiguous genes can be precisely characterized by array CGH.

PMID- 19400879
TI  - Mapping brain activity on the verge of a photically induced generalized tonic
      clonic seizure.
AB  - In a photosensitive patient intermittent photic stimulation (IPS) accidentally
      provoked a generalized tonic-clonic seizure during simultaneous recordings of
      electroencephalography (EEG) and functional magnetic resonance imaging (fMRI).
      Before seizure onset, IPS consistently induced generalized photoparoxysmal
      responses (PPRs). These PPRs were associated with increases in blood oxygen level
      dependent (BOLD) signal in the visual cortex, the thalamus, and both superior
      colliculi, and a decrease in BOLD signal in the frontoparietal areas. The BOLD
      signal in the visual cortex increased in magnitude during consecutive epochs of
      IPS associated with PPRs. We propose that repeated IPS led to an excessive amount
      of neuronal activity in the visual cortex that evoked PPRs and finally exceeded a
      critical threshold and triggered a generalized seizure.

PMID- 19400880
TI  - Subfield atrophy pattern in temporal lobe epilepsy with and without mesial
      sclerosis detected by high-resolution MRI at 4 Tesla: preliminary results.
AB  - PURPOSE: High-resolution magnetic resonance imaging (MRI) at 4 Tesla depicts
      details of the internal structure of the hippocampus not visible at 1.5 Tesla,
      and so allows for in vivo parcellation of different hippocampal subfields. The
      aim of this study was to test if distinct subfield atrophy patterns can be
      detected in temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE-MTS)
      and without (TLE-no) hippocampal sclerosis. METHODS: High-resolution T(2)
      weighted hippocampal images were acquired in 34 controls: 15 TLE-MTS and 18 TLE
      no. Entorhinal cortex (ERC), subiculum (SUB), CA1, CA2, and CA3, and dentate
      (CA3&DG) volumes were determined using a manual parcellation scheme. RESULTS: TLE
      MTS had significantly smaller ipsilateral CA1, CA2, CA3&DG, and total hippocampal
      volume than controls or TLE-no. Mean ipsilateral CA1 and CA3&DG z-scores were
      significantly lower than ipsilateral CA2, ERC, and SUB z-scores. There were no
      significant differences between the various subfield or hippocampal z-scores on
      either the ipsi- or the contralateral side in TLE-no. Using a z-score <or=-2.0 to
      identify severe volume loss, the following atrophy patterns were found in TLE
      MTS: CA1 atrophy, CA3&DG atrophy, CA1 and CA3&DG atrophy, and global hippocampal
      atrophy. Significant subfield atrophy was found in three TLE-no: contralateral
      SUB atrophy, bilateral CA3&DG atrophy, and ipsilateral ERC and SUB atrophy.
      DISCUSSION: Using a manual parcellation scheme on 4 Tesla high-resolution MRI, we
      found the characteristic ipsilateral CA1 and CA3&DG atrophy described in TLE-MTS.
      Seventeen percent of the TLE-no had subfield atrophy despite normal total
      hippocampal volume. These findings indicate that high-resolution MRI and subfield
      volumetry provide superior information compared to standard hippocampal
      volumetry.

PMID- 19400881
TI  - Striae distensae (stretch marks) and different modalities of therapy: an update.
AB  - BACKGROUND: Striae distensea (SD; stretch marks) are a well-recognized, common
      skin condition that rarely causes any significant medical problems but are often
      a significant source of distress to those affected. The origins of SD are poorly
      understood, and a number of treatment modalities are available for their
      treatment, yet none of them is consistently effective, and no single therapy is
      considered to be pivotal for this problem. With a high incidence and
      unsatisfactory treatments, stretch marks remain an important target of research
      for an optimum consensus of treatment. OBJECTIVE: To identify the current
      treatment modalities and their effectiveness in the treatment of stretch marks.
      MATERIALS AND METHODS: Review of the recent literature regarding clinical
      treatment of stretch marks with emphasis on the safety and efficacy of the newer
      optical devices and laser applications. RESULTS: No current therapeutic option
      offers complete treatment, although there are a number of emerging new modalities
      that are encouraging. CONCLUSION: The therapeutic strategies are numerous, and no
      single modality has been far more consistent than the rest. The long-term future
      of treatment strategies is encouraging with the advance in laser technologies.

PMID- 19400882
TI  - Suction blister epidermal grafts combined with CO2 laser superficial ablation as
      a good method for treating small-sized vitiligo.
AB  - BACKGROUND: Despite the availability of various new methods to treat vitiligo,
      surgical methods offer rapid, simple, and safe ways for treating small-sized
      vitiligo. OBJECTIVE: To evaluate the feasibility and efficacy in treating
      vitiligo using suction blister epidermal grafting (SBEG) combined with CO2 laser
      epidermal ablation. METHODS: Forty patients with small, stable vitiligo were
      treated using SBEG combined with CO2 laser epidermal ablation and followed up for
      at least 6 months and up to 10 years. RESULTS: Treatment outcomes were excellent
      for 32 patients (80%), good for four patients (10%), fair for three patients
      (7.5%), and poor for one patient (2.5%). No scar formation was observed in any
      patients. Location of the lesions was probably the most important factor in
      determining the outcomes of transplantation. CONCLUSION: This study suggests that
      SBEG combined with CO2 laser ablation is a rapid, simple, and safe method to
      treat vitiligo, especially for patients with small and stable vitiliginous
      lesions.

PMID- 19400883
TI  - The tissue efficiency of common reconstructive design and modification.
AB  - BACKGROUND: Facial reconstructive techniques are capable of restoring a normal
      anatomic appearance despite the tissue loss resulting from skin cancer removal.
      Because none of these techniques recreate the lost tissue, most of these
      techniques require the removal of additional normal tissue in the form of Burow's
      triangles to achieve this goal. OBJECTIVE: To analyze the quantity and potential
      variability of redundant tissue loss encountered during the use of conventional
      reconstructive techniques through the calculation of tissue efficiency. METHODS:
      Conventional reconstructive designs were applied to a standard circular defect
      using computer-aided design software to determine the surface area of each
      closure design. Tissue efficiency was defined as the surface area of the defect
      divided by the total surface area of tissue loss after reconstruction. RESULTS:
      Island pedicle flaps (78.5%) and rhombic flaps (68.0%) offer the highest degree
      of tissue conservation among conventional flap designs. CONCLUSIONS: The majority
      of flap designs offer a significant improvement in tissue efficiency over the
      standard linear closure; they simply result in less overall tissue loss. A number
      of design modifications can limit or even reduce additional tissue loss while
      gaining significant advantages in flap mobility or tissue recruitment.

PMID- 19400884
TI  - Randomized nonblinded comparison of convalescence for 2 and 7 days after split
      thickness skin grafting to the lower legs.
AB  - BACKGROUND: There is an increasing expectation of shortened postoperative
      recovery times and a suggestion that shorter convalescence times may not
      compromise lower leg split-thickness skin graft results. OBJECTIVE: To determine
      whether mobilization after 2 days of convalescence compromises graft survival or
      patient morbidity. METHODS AND MATERIALS: A pilot study was initiated in which
      patients undergoing split-thickness skin grafting to the lower legs were
      randomized to 2 or the routine 7 days of convalescence. Baseline characteristics
      were determined, and patients were followed up in dressing clinics and with a
      standardized telephone interview. RESULTS: There was no difference in baseline
      patient comorbidities and no significant difference in the number of grafts lost,
      the number of dressing clinics, bleeding, or wound infections. CONCLUSION: The
      results suggest that 2 days of convalescence after split-thickness skin grafting
      to the lower legs may not compromise graft survival or increase patient
      morbidity. Further study with larger numbers is required to confirm this finding.

PMID- 19400885
TI  - Effectiveness, safety, and effect on quality of life of topical salicylic acid
      peels for treatment of postinflammatory hyperpigmentation in dark skin.
AB  - BACKGROUND: There are no randomized split-face model studies investigating
      treatments for postinflammatory hyperpigmentation (PIH) in dark skin. OBJECTIVE:
      To assess the efficacy, safety, and effect on quality of life of salicylic acid
      peels for PIH in dark skin. METHODS: Ten subjects with Fitzpatrick skin
      phototypes IV to VI were randomized to receive two 20% salicylic acid peels
      followed by three 30% salicylic acid peels to half of the face. The contralateral
      half remained untreated. Response was evaluated by photography reviewed by three
      blinded dermatologists. The Visual Analog Scale, Dermatology Life Quality Index
      (DLQI), and treatment quality questionnaire were administered. RESULTS:
      Improvement of PIH on the treatment side according to each rater (p=.81, p=.81,
      p=.42) and according to the raters combined (p=.11) approached but did not reach
      statistical significance. Subjects' Visual Analog Scale scores indicated
      significantly greater improvement of PIH on the treatment side than in the
      control (p=.004). Quality of life measured according to the DLQI improved after
      treatment but not statistically significantly so (p=.13). Treatment had no
      significant adverse effects. CONCLUSIONS: Salicylic acid peels are safe in this
      population. Although patients rated them as clinically effective, blinded raters
      found a brief series of peels to have less efficacy. Measured quality of life
      improved nominally.

PMID- 19400886
TI  - Use of the TrichoScan to assess female pattern hair loss.
AB  - BACKGROUND: TrichoScan is a method of hair growth measurement that combines
      epiluminescence microscopy with automatic digital image analysis. Miniaturization
      is considered a cornerstone of androgenetic alopecia (AGA) and is requisite for
      establishing the diagnosis. OBJECTIVE: To examine miniaturization in women with
      AGA. METHODS AND PATIENTS: Twenty-eight women with Ludwig pattern (aged 21-68,
      mean 46) were included. Miniaturization was estimated using the TrichoScan
      method. RESULTS: Almost one-quarter (21.4%) of the women had miniaturized hair
      only on the top of the head (the crown), 28.6% had miniaturized hair throughout
      the scalp, and 50.0% showed no miniaturization but a preponderance of thinning in
      the crown area. In all patients, a comparative study of hair diameter revealed
      significant differences between the crown and the occipital region. CONCLUSIONS:
      Our results imply that, in female hair loss, miniaturization might be a relative
      and not an absolute measurement, and AGA in women could be diagnosed also in the
      presence of a difference in hair shaft diameter.

PMID- 19400887
TI  - The interpolated paranasal flap: a novel and advantageous option for nasal-alar
      reconstruction.

PMID- 19400888
TI  - Treatment of the patient with nevoid basal cell carcinoma syndrome in a
      megasession.

PMID- 19400889
TI  - Euthyroid nodular pretibial mucinosis: palliative treatment with carbon dioxide
      laser.

PMID- 19400890
TI  - Regarding complete spontaneous regression of Merkel cell carcinoma.

PMID- 19400891
TI  - Infrared irradiation as an adjuvant therapy in recalcitrant alopecia areata.

PMID- 19400893
TI  - Safety of hookworm infection in individuals with measurable airway
      responsiveness: a randomized placebo-controlled feasibility study.
AB  - BACKGROUND: Epidemiological evidence suggests that hookworm infection protects
      against asthma. However, for ethical and safety reasons, before testing this
      hypothesis in a clinical trial in asthma it is necessary to establish whether
      experimental hookworm infection might exacerbate airway responsiveness during
      larval lung migration. OBJECTIVE: To determine whether hookworm larval migration
      through the lungs increases airway responsiveness in allergic individuals with
      measurable airway responsiveness but not clinical asthma, and investigate the
      general tolerability of infection and effect on allergic symptoms. METHODS:
      Thirty individuals with allergic rhinoconjunctivitis and measurable airway
      responsiveness to adenosine monophosphate (AMP) but not clinically diagnosed
      asthma were randomized, double-blind to cutaneous administration of either 10
      hookworm larvae or histamine placebo, and followed for 12 weeks. The primary
      outcome was the maximum fall from baseline in provocative dose of inhaled AMP
      required to reduce 1-s forced expiratory volume by 10% (PD(10)AMP) measured at
      any time over the 4 weeks after active or placebo infection. Secondary outcomes
      included peak flow variability in the 4 weeks after infection,
      rhinoconjunctivitis symptom severity and adverse effect diary scores over the 12
      week study period, and change in allergen skin test responses between baseline
      and 12 weeks. RESULTS: Mean maximum change in PD(10)AMP from baseline was
      slightly but not significantly greater in the hookworm than the placebo group (
      1.67 and -1.16 doubling doses; mean difference -0.51, 95% confidence interval 
      1.80 to 0.78, P=0.42). Symptom scores of potential adverse effects were more
      commonly reported in the hookworm group, but infection was generally well
      tolerated. There were no significant differences in peak-flow variability,
      rhinoconjunctivitis symptoms or skin test responses between groups. CONCLUSION:
      Hookworm infection did not cause clinically significant exacerbation of airway
      responsiveness and was well tolerated. Suitably powered trials are now indicated
      to determine the clinical effectiveness of hookworm infection in allergic
      rhinoconjunctivitis and asthma.

PMID- 19400894
TI  - Prevalence of immunoglobulin E-mediated food allergy in 6-9-year-old urban
      schoolchildren in the eastern Black Sea region of Turkey.
AB  - BACKGROUND: The prevalence of adverse reactions to food in childhood in Turkey is
      not known. OBJECTIVE: We aimed to investigate the prevalence and characteristics
      of IgE-mediated food allergies (FAs) in 6-9-year-old urban schoolchildren.
      METHODS: This cross-sectional study recruited 3500 of the randomly selected 6-9
      year-old urban schoolchildren from the eastern Black Sea region of Turkey during
      2006. Following a self-administered questionnaire completed by the parents and
      the child, consenting children were invited for skin prick tests (SPTs) and oral
      food challenges. Children with suspected IgE-mediated FA were skin prick tested
      with a predefined panel of food allergens (milk, hen's egg, soy, wheat, peanut,
      fish, and hazelnut), aeroallergens (Dermatophagoides pteronyssinus,
      Dermatophagoides farinae, cat, dog, Alternaria, grass pollen mix, weed pollen
      mix, and tree pollen mix), and food allergens reported in the questionnaire. All
      children with a positive SPT to any food were invited for a double-blind, placebo
      controlled food challenge (DBPCFC). The prevalence of IgE-mediated FA was
      established using DBPCFCs. RESULTS: The response rate to the questionnaire was
      78.2% (2739/3500). The estimated prevalence of parental-reported IgE-mediated FA
      was 5.7% (156/2739) [95% confidence interval (CI), 4.83-6.57%]. The rate of
      sensitization to the food allergens was 33.1% (48/145) in the parental-reported
      group. The confirmed prevalence of IgE-mediated FA by means of DBPCFC in 6-9-year
      old urban schoolchildren living in the eastern Black Sea region of Turkey was
      0.80% (22/2739) (95% CI, 0.47-1.13%). The most common allergenic foods were beef
      (31.8%), cow's milk (18.1%), cocoa (18.1%), hen's egg (13.6%), and kiwi (13.6%).
      CONCLUSIONS: The rate of reported IgE-mediated FA was significantly higher than
      clinically confirmed FA by means of DBPCFC (odds ratio, 7.46; 95% CI, 4.67-12.01;
      P<0.0001). The order of allergenic foods was different and somewhat unique to the
      eastern Black Sea region of Turkey when compared with western countries.

PMID- 19400895
TI  - T cells and eosinophils in bronchial smooth muscle cell death in asthma.
AB  - BACKGROUND: Bronchial smooth muscle cells (SMC) proliferate, express adhesion
      molecules, secrete cytokines and thus efficiently contribute to the pathogenesis
      of asthma. OBJECTIVE: The aim of the study was to investigate whether, and by
      which mechanism, T cells and eosinophils can cause death of airway SMC. METHODS:
      The T cell- and eosinophil-induced cell death was analysed in primary human
      bronchial SMC cultures as well as in bronchial biopsy specimens from non
      asthmatic and asthmatic individuals. RESULTS: Bronchial SMC death showed
      characteristic morphological features of apoptosis in 3-6 days cultures with
      inflammatory cytokines (IFN-gamma, TNF-alpha), soluble death ligands [sFasL, TNF
      related apoptosis-inducing ligand (TRAIL)] and activated T-helper type 1 (Th1)
      and Th2 cell supernatants. The recombinant eosinophil cationic protein induced
      SMC necrosis within 1 h. Resting SMC expressed the death receptors TNFR1, TNFR2,
      Fas, TRAILR1, TRAILR2 and membrane FasL as a death-inducing ligand. IFN-gamma and
      TNF-alpha up-regulated TNFR1, TNFR2, Fas and membrane FasL on SMC. TNF-alpha up
      regulated TRAILR1 and TRAILR2; sFasL up-regulated TNFR2. The intracellular
      caspase-3 activation in SMC was significantly increased by IFN-gamma, sFasL,
      TRAIL, Th1 and Th2 cell supernatants. Increased expression of TRAIL in
      asthmatics, but not in non-asthmatic individuals was demonstrated in situ. The
      apoptosis receptors TRAILR1 and TRAILR2 were expressed in SMC and epithelial
      cells both in healthy and asthmatic biopsies. Prominent apoptosis of SMC was
      observed in fatal asthma, but not intermittent asthma biopsies. CONCLUSION: The
      demonstration of bronchial SMC death both by apoptosis and necrosis indicates the
      essential role of T cells and eosinophils in the bronchial tissue injury
      particularly in the severe asthma.

PMID- 19400897
TI  - Anti-bacterial IgE in the antibody responses of house dust mite allergic children
      convalescent from asthma exacerbation.
AB  - BACKGROUND: Atopic sensitization to the house dust mite (HDM) is associated with
      altered antibody responses to the nasopharyngeal colonizing bacterium Haemophilus
      influenzae and children admitted to the emergency department for asthma
      exacerbation have reduced IgG responses to HDM allergens. OBJECTIVE: To
      investigate anti-bacterial and anti-allergen antibody responses during
      convalescence from asthma exacerbation and differences found in exacerbations
      associated with and without viral infection. RESULTS: IgE antibodies to the P6
      bacterial antigen increased in 60% of sera during convalescence and for many
      children achieved titres as high as IgE titres to allergens. In contrast IgE anti
      HDM titres declined during convalescence. The anti-bacterial IgE titres were the
      same in subjects with and without virus infection while the anti-HDM IgE declined
      more rapidly in virus-infected subjects. IgG titres to the major HDM allergens
      showed no consistent increase and the overall IgG anti-HDM titres even declined
      in subjects without a virus infection. Anti-bacterial IgG antibodies in contrast
      to IgE did not change. Patients with frequent episodic or persistent asthma had
      similar IgE anti-bacterial titres to patients with infrequent asthma during the
      acute phase, although they had reduced IgG titres to both the bacteria and the
      HDM. CONCLUSIONS: During the period following an acute exacerbation of asthma
      there was a marked and specific increase in anti-bacterial IgE compared with a
      reduced IgE response to HDM. This provides further support for the concept of T
      helper type 2 responses to bacterial antigens playing a role in asthma
      pathogenesis.

PMID- 19400896
TI  - Cleaved secretory leucocyte protease inhibitor as a biomarker of chymase activity
      in allergic airway disease.
AB  - BACKGROUND: Secretory leucocyte protease inhibitor (SLPI), which is present in
      many physiological fluids including saliva, sputum and nasal discharge, is the
      most effective inhibitor of chymase. Previously, we demonstrated that chymase is
      able to cleave SLPI and that the cleaved portion, cSLPI, is a biomarker of
      chymase activity. OBJECTIVE: We investigated the potential of cSLPI as a
      biomarker of chymase activity in subjects with allergic rhinitis (AR) and
      asthmatic airway disease. METHODS: Baseline sputum samples were collected from
      atopic asthmatics and healthy controls (HC). Nasal lavages (NAL) were performed
      in subjects with AR both at baseline and following a nasal challenge with
      allergen or placebo. Levels of cSLPI and chymase were determined by Western
      analysis, and tryptase and alpha-2 macroglobulin were measured by immunoassay.
      RESULTS: As compared with HC, asthmatics showed a significant increase in
      baseline cSLPI/total SLPI ratios and an increase in chymase levels. There was a
      high correlation of cSLPI/SLPI ratios to chymase levels in normal individuals and
      untreated asthmatics. In the NAL of patients with AR, as compared with placebo,
      allergen challenge increased inflammatory biomarkers, including cSLPI/SLPI
      ratios, chymase levels, tryptase levels and alpha2-macroglobulin levels.
      Correlations were observed between cSLPI/SLPI ratios and chymase levels and
      cSLPI/SLPI ratios and alpha2-macroglobulin levels; no correlation was seen
      between cSLPI/SLPI ratios and tryptase levels. CONCLUSION: Our data indicate that
      cSLPI reflects chymase activity in AR and asthma. Hence, cSLPI may serve as a
      biomarker for disease activity and for monitoring the efficacy of novel anti
      inflammatory treatments in chymase-mediated diseases.

PMID- 19400898
TI  - Predicting the outcome of oral food challenges with hen's egg through skin test
      end-point titration.
AB  - BACKGROUND: Oral food challenge (OFC) is the diagnostic 'gold standard' of food
      allergies but it is laborious and time consuming. Attempts to predict a positive
      OFC through specific IgE assays or conventional skin tests so far gave suboptimal
      results. OBJECTIVE: To test whether skin test with titration curves predict with
      enough confidence the outcome of an oral food challenge. METHODS: Children (n=47;
      mean age 6.2 +/- 4.2 years) with suspected and diagnosed allergic reactions to
      hen's egg (HE) were examined through clinical history, physical examination, oral
      food challenge, conventional and end-point titrated skin tests with HE white
      extract and determination of serum specific IgE against HE white. Predictive
      decision points for a positive outcome of food challenges were calculated through
      receiver operating characteristic (ROC) analysis for HE white using IgE
      concentration, weal size and end-point titration (EPT). RESULTS: OFC was positive
      (Sampson's score >or=3) in 20/47 children (42.5%). The area under the ROC curve
      obtained with the EPT method was significantly bigger than the one obtained by
      measuring IgE-specific antibodies (0.99 vs. 0.83, P<0.05) and weal size (0.99 vs.
      0.88, P<0.05). The extract's dilution that successfully discriminated a positive
      from a negative OFC (sensitivity 95%, specificity 100%) was 1 : 256,
      corresponding to a concentration of 5.9 microg/mL of ovotransferrin, 22.2
      microg/mL of ovalbumin, and 1.4 microg/mL of lysozyme. CONCLUSION: EPT is a
      promising approach to optimize the use of skin prick tests and to predict the
      outcome of OFC with HE in children. Further studies are needed to test whether
      this encouraging finding can be extended to other populations and food allergens.

PMID- 19400899
TI  - Establishing the incidence and prevalence of clinician-diagnosed allergic
      conditions in children and adolescents using routinely collected data from
      general practices.
AB  - BACKGROUND: There remains a need to better characterize the epidemiology of
      allergic disorders, particularly in relation to describing the incidence, natural
      history and co-morbidity of allergic conditions. OBJECTIVES: To estimate the
      incidence and prevalence of clinician-diagnosed eczema, asthma and rhinitis,
      alone and in combination, in children and adolescents in the United Kingdom.
      METHODS: Using the national General Practice Research Database (GPRD) - one of
      the largest validated databases of routinely collected healthcare data in the
      world aggregating 3.6 million individuals - we constructed a retrospective birth
      cohort of 43,473 children born in the year 1990 and registered with a UK general
      practice within a year of birth. The cohort was followed until 2008 or the
      longest available follow-up period to determine the cumulative and age-specific
      incidence and prevalence rates of clinician-diagnosed eczema, asthma and
      rhinitis, and an 18-year prevalence of these conditions, alone and in
      combination. RESULTS: Eczema had the highest incidence density of 226.9 per
      10,000 person-years [95% confidence interval (CI): 225.8-228.0] followed by
      asthma [136.6;(95% CI: 135.7-137.5)] and rhinitis [61.4;(95% CI: 60.8-62.0)], by
      the age of 18 years. The incidence densities of suffering from one, two or all
      three allergic conditions were 323.2 (95% CI: 322.0-324.4), 206.4 (95% CI: 205.7
      207.1) and 141.9 (95% CI: 141.4-142.4) per 10,000 person-years, respectively.
      Among the 24 112 children with a complete 18-year follow-up, eczema had the
      highest 18-year prevalence of clinician-diagnosed condition at 36.5% (95% CI:
      35.9-37.2%) followed by asthma [22.9;(95% CI: 22.3-23.4%)] and rhinitis[11.4;(95%
      CI: 11.0-11.8%)]. The 18-year prevalence of more than one and all three
      conditions was 16.1% (95% CI: 15.6-16.6%) and 2.5% (95% CI: 2.4-2.8%),
      respectively. CONCLUSIONS: This is one of the first studies to provide national
      estimates on the age-specific incidence and age-specific prevalence of the major
      allergic disorders showing clinician-diagnosed eczema, asthma and rhinitis to
      have high incidence rates in early childhood. A significant proportion of
      children experience and are diagnosed with multiple allergic conditions in early
      childhood.

PMID- 19400900
TI  - Chitinases and chitinase-like proteins: potential therapeutic targets for the
      treatment of T-helper type 2 allergies.
AB  - Mammalian chitinase and chitinase-like proteins (CLPs) are a family of mediators
      increasingly associated with infection, T cell-mediated inflammation, wound
      healing, allergy and asthma. Although our current knowledge of the function of
      mammalian chitinases and CLPs is very limited, important information can be
      deduced from research carried out in lower organisms, and in different
      immunopathological conditions. Enzymatically active mammalian chitinase proteins
      may have evolved to degrade the copious amounts of chitin mammals are exposed to
      on a daily basis, and to form an innate barrier to chitin-containing organisms.
      CLPs are homologous to chitinases but lack the ability to degrade chitin. It is
      most striking that both chitinases and CLPs are up-regulated in T-helper type 2
      (Th2)-driven conditions, and the first evidence is now emerging that these
      proteins may accentuate Th2 reactivity, and possibly contribute to the repair
      process that follows inflammation. Following studies demonstrating that chitinase
      inhibition leads to an attenuated allergic response, several strategies are being
      used to develop enzyme inhibitors for therapeutic use in human diseases. In this
      review, we will summarize recent insights into the effects of chitinases and CLPs
      in the context of Th2-dominated pathology with particular focus on allergy and
      asthma, discussing whether chitinase enzyme inhibitors may be of therapeutic
      value.

PMID- 19400901
TI  - Engineering of major house dust mite allergens Der p 1 and Der p 2 for allergen
      specific immunotherapy.
AB  - BACKGROUND: Specifically designed recombinant allergens with reduced IgE
      reactivity are promising candidates for a more defined, effective, and safer
      specific immunotherapy (SIT). OBJECTIVE: We sought to obtain hypoallergenic
      hybrid molecules which could potentially be applied to house dust mite (HDM)
      allergy treatment. METHODS: Two hybrid molecules (QM1 and QM2) derived from the
      two major Dermatophagoides pteronyssinus allergens, Der p 1 and Der p 2, were
      engineered by PCR, produced in Escherichia coli, and purified. The overall IgE
      binding capacity of the hybrids was compared with their single components by
      Western blot, specific IgE, skin prick test (SPT), and IgE-inhibition assays. T
      cell proliferation assay were performed to confirm their retention of T cell
      reactivity. Immune responses to the hybrid molecules were studied in BALB/c mice.
      RESULTS: The IgE reactivity of both hybrid proteins was strongly reduced as
      evaluated by in vitro methods. Furthermore, in vivo SPTs performed on 106 HDM
      allergic patients showed that the hybrid proteins had a significantly lower
      potency to induce cutaneous reactions than the individual components. Hybrid
      molecules induced higher T cell proliferation responses than those produced by an
      equimolecular mixture of Der p 1 and Der p 2. Immunization of mice with the
      hybrid proteins induced Der p 1- and Der p 2-specific IgG, which inhibited the
      binding of allergic patients' IgE to these natural allergens. CONCLUSION: QM1 and
      QM2 hybrids exhibited less IgE-binding activity but preserved immunogenicity and
      fulfilled the basic requirements for hypoallergenic molecules suitable for a
      future SIT of HDM allergy.

PMID- 19400902
TI  - Non-atopic intrinsic asthma and the 'family tree' of chronic respiratory disease
      syndromes.
AB  - We present a scheme below in which the most common forms of inflammatory diseases
      of the respiratory tract, notably atopic and non-atopic asthma and COPD, are
      depicted as separate offshoots from a common 'at-risk' pathway underpinned by
      genotypes related to aberrations in control of host defence and tissue repair
      mechanisms. We propose that entrance into this pathway is initially programmed by
      environmental experience during infancy and early childhood, in particular by
      severe lower respiratory tract infection, and that further progression towards
      expression of specific disease phenotype(s) is determined by the nature, timing
      and frequency of additional environmental insults subsequently encountered. At
      the one extreme, early sensitization of at-risk subjects to aeroallergens can
      potentially drive rapid progression towards expression of the atopic asthmatic
      phenotype under the dual onslaught of inflammatory responses to
      allergens/pathogens. At the opposite end of the spectrum the drip-feed effects of
      occasional infections on respiratory function(s) are amplified over a longer time
      frame by inflammation resulting from exposure to tobacco smoke and/or related
      chemical pollutants. Non-atopic asthma is envisaged to fit between these two
      extremes, being driven essentially by the downstream effects of respiratory
      infections alone in at-risk subjects. An important common factor in all three
      disease phenotypes is that acute exacerbations are typically driven by
      infections, the host responses to which display a characteristic T-helper type 2
      like footprint, which in our view points to underlying genotype(s) which result
      in unbalanced host responses to respiratory pathogens.

PMID- 19400903
TI  - Transforming growth factor-beta in allergic inflammatory disease of the upper
      airways: friend or foe?
AB  - TGF-beta is a multi-functional cytokine with a huge array of effects on a variety
      of cell types. It is rapidly emerging as a key major player in the way the airway
      epithelium behaves and its ability to repair itself. This is not only of
      relevance to allergic airway diseases such as asthma and allergic rhinitis, which
      are increasing in prevalence worldwide, but in many other diseases. The full
      impact any disruption of TGF-beta signalling may have in the development and
      persistence of allergic inflammatory airway diseases is yet to be fully realized
      and remains the subject of ongoing research. There has been a recent revival of
      interest in the role of regulatory T cells in controlling allergic inflammation.
      Evidence is emerging of a significant contribution by TGF-beta to this regulatory
      process. This review aims to summarize current knowledge relating to TGF-beta in
      relation to allergic inflammatory upper airways disease, and attempts to clarify
      some of the discrepancies and inconsistencies in this area. It also considers the
      therapeutic implications of novel TGF-beta therapy, including potential future
      applications in the treatment of nasal polyposis and reduction of post-operative
      scar tissue formation following endoscopic sinus surgery.

PMID- 19400904
TI  - Gamma-aminobutyric acid nurtures allergic asthma.
AB  - Asthma often occurs as a result of immune-based inflammatory responses, which
      consequently cause pathological changes in airway structural cells. However, the
      underlying mechanisms of airway pathology in asthma are still not fully
      understood. Our recent studies revealed a critical role of gamma-aminobutyric
      acid (GABA) signalling pathway in the airway epithelium of allergic asthma
      through its ability to stimulate mucus production. This review briefly describes
      the GABAergic signalling system and its role in the regulation of mucus protein
      production in bronchial airway epithelial cells.

PMID- 19400905
TI  - Pathogenesis of chronic urticaria.
AB  - Chronic urticaria is defined as the presence of urticaria (hives) for at least 6
      weeks with the assumption that it occurs daily or close to it. If we eliminate
      physical urticarias and urticarial vasculitis from consideration, the remainder
      can be divided into autoimmune chronic urticaria (45%) and idiopathic chronic
      urticaria (55%). The autoimmune subgroup is associated with the IgG anti-IgE
      receptor alpha subunit in 35-40% of patients and IgG anti-IgE in an additional 5
      10%. These autoantibodies have been shown to activate blood basophils and
      cutaneous mast cells in vitro with augmentation of basophil activation by
      complement and release of C5a, in particular. Binding methods (immunoblot and
      ELISA) yield positives in many autoimmune diseases as well as occasional normal
      subjects or patients with other forms of urticaria but most such sera are non
      functional. Activation of basophils or mast cells causing histamine release is
      quite specific for chronic urticaria and defines the autoimmune subgroup.
      Although pathogenicity is not formally proven, the antibodies cause wealing upon
      intradermal injection, and removal of the autoantibody leads to remission. A
      cellular infiltrate is seen to be characterized by mast cell degranulation and
      infiltration of CD4+ T lymphocytes, monocytes, neutrophils, eosinophils, and
      basophils. The intensity of the infiltrate and clinical severity of the disease
      (including accompanying angio-oedema) is more severe in the autoimmune
      subpopulation. This latter group also has a higher evidence of human leucocyte
      antigen DR alleles associated with autoimmunity and a 25% incidence of
      antithyroid antibodies with diagnosed hypothyroidism in some. Hypo-responsiveness
      of patients' basophils to anti-IgE and hyperresponsiveness to serum defines
      another subpopulation (at least 50%) that overlaps the idiopathic and autoimmune
      subgroups. Hypo-responsiveness to anti-IgE has been shown to be associated with
      elevated levels of cytoplasmic phosphatases that inhibit degranulation. Reversal
      of the abnormality is seen with disease remission. Further work will be needed to
      distinguish whether this is a cause or a consequence of persistent urticaria and
      to further assess the relationship (or lack thereof) of altered responsiveness
      (decreased or increased) with the presence or absence of activating
      autoantibodies.

PMID- 19400906
TI  - Osteopontin is involved in migration of eosinophils in asthma.
AB  - BACKGROUND: Osteopontin (OPN) is an extracellular matrix protein with a wide
      range of functions, and is involved in various inflammatory diseases. However,
      the role of OPN in eosinophilic airway inflammation is unclear. OBJECTIVE: To
      elucidate the role of OPN in eosinophilic airway inflammation. METHODS: OPN
      protein levels in induced sputum from asthmatic patients and healthy controls
      were measured. Eosinophil migration assays were performed in the presence or
      absence of OPN, a blocking antibody (Ab) recognizing its integrin-binding domain
      (2K1) and an anti-integrin alpha 4 Ab (P1H4). In the mouse asthma model, the
      levels of eosinophilia were examined in bronchoalveolar lavage fluids (BALFs)
      from ovalbumin (OVA)-sensitized and -challenged mice with or without
      administration of an Ab (M5) corresponding to human 2K1. RESULTS: Levels of OPN
      in induced sputum were significantly higher in asthmatic patients when compared
      with healthy controls. In addition, levels of OPN were correlated with the
      percentage of sputum eosinophils. OPN induced significant migration of human
      eosinophils and this effect was inhibited by 2K1 and P1H4. M5 significantly
      attenuated OVA-induced eosinophilia in BALFs. CONCLUSION: These results indicate
      that OPN plays a role in the migration of eosinophils into the airways and may be
      involved in the pathogenesis of asthma.

PMID- 19400907
TI  - Elevated baseline serum tryptase, mastocytosis and anaphylaxis.

PMID- 19400909
TI  - Allergen dose dependency of the early- and late-phase cutaneous response in the
      cynomolgus monkey.
AB  - BACKGROUND: Cutaneous administration of allergen provides a means to confirm an
      allergic status, investigate the pathogenesis of allergic diseases, and/or
      provide a mechanism to evaluate the benefit of new potential therapeutics.
      OBJECTIVE: Studies were performed to characterize the allergen-induced cutaneous
      early- and late-phase response (EPR and LPR) in the cynomolgus monkey. METHODS:
      Following intradermal injections of Ascaris suum allergen, the cutaneous weal and
      flare EPR was measured 15 min post-injection, and skin biopsies were collected at
      8-24 h to determine the optimal time of LPR occurrence. Biopsies were analysed
      for epidermal and dermal inflammatory changes. RESULTS: The EPR was dose related
      with a reproducible, measurable response at 1 : 10 000 and maximal at a 1 : 100
      allergen dilution. In contrast, the threshold dose required for a reproducible
      LPR was much greater requiring a dilution of 6 : 100, suggesting independent
      mechanisms for the EPR and LPR. The LPR 20 h post-allergen injection induced an
      inflammatory response in the upper and deep dermis. The response was
      characterized by a moderate perivascular to diffuse inflammation consisting of
      mononuclear cells, neutrophils and eosinophils. Dexamethasone, while having no
      effect on the EPR, reduced dermal inflammation (upper dermis, P=0.004; deep
      dermis, P=0.03). Similarly, dermal eosinophilia was also reduced (upper dermis,
      P<0.001; deep dermis, P=0.02). CONCLUSION: Collectively, the results indicate the
      dose dependency of the EPR and LPR. Furthermore, our observations indicate the
      value of the LPR response in the cynomolgus monkey to evaluate new therapeutics
      for the treatment of allergic diseases such as atopic dermatitis.

PMID- 19400908
TI  - Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic
      responses.
AB  - Allergic diseases are often triggered by environmental allergens that induce
      dominant type 2 immune responses, characterized by the infiltrated T-helper type
      2 (TH2) lymphocytes, eosinophils, and elevated TH2 cytokines. In addition to TH2
      type immune responses, epithelial stress and injury linked to tissue remodelling
      are often observed, suggesting that epithelial cells may play important role in
      regulating allergic responses. Dendritic cells (DCs), the professional antigen
      presenting cells with the capabilities of sampling allergens, are considered as
      the key player on instructing TH2 immune responses. Whether inflamed epithelium
      can regulate innate immunity, such as macrophages and DCs, which in turn
      instructs adaptive immunity has long been hypothesized. Studies of thymic stromal
      lymphopoietin (TSLP), an epithelial cells-derived cytokine, that can strongly
      activate DCs, provide important evidences that the epithelial barrier can trigger
      allergic diseases by regulating immune responses. The finding that
      OX40/OX40Ligand (OX40L) interactions are the molecular trigger responsible for
      the induction and maintenance of TH2 responses by TSLP-activated DCs provides a
      plausible molecular explanation for TSLP-mediated allergy. Recent progresses in
      characterizing the pro-inflammatory IL-17 cytokine family have added an
      additional layer of complexity on the regulation of allergic inflammation. TSLP
      DCs can induce a robust expansion of TH2 memory cells and strengthen functional
      attributes by up-regulating their surface expression of IL-17RB (IL-25R), the
      receptor for cytokine IL-17E (IL-25), a distinct member of IL-17 cytokine family.
      IL-17E (also known as IL-25) produced by epithelial cells, and other innate
      cells, such as eosinphils, basophils, and mast cells, are shown to regulate
      adaptive immunity by enhancing TH2 cytokine productions. These exciting findings
      expand our knowledge of the complex immunological cascades that result in
      allergic inflammation and may provide novel therapeutic approaches for the
      treatment of allergic diseases.

PMID- 19400910
TI  - Immunoglobulin E-mediated immediate allergic reactions to dipyrone: value of
      basophil activation test in the identification of patients.
AB  - BACKGROUND: Pyrazolones are a major cause of immediate IgE-mediated reactions to
      drugs in many countries. OBJECTIVE: The aim of the study was to evaluate a group
      of patients with this type of reaction by basophil activation test (BAT),
      focusing on the influence on positivity of the time between the reaction and this
      study. METHODS: The study included 51 patients with selective immediate allergic
      reactions to pyrazolones and 56 controls. Patients were defined by skin testing
      or a drug provocation test and BATs with pyrazolones were carried out in all
      cases. Patients who were BAT positive were followed-up for 30 months to establish
      the rate of decline in positive tests. RESULTS: BAT was positive in 28 (54.9%)
      cases. BAT sensitivity was higher in those who were skin-test positive (85.7%)
      compared with those who were skin-test negative (33.3%). The time between the
      initial reaction and this study was significantly shorter in those who were skin
      test positive (P=0.005) and those who were BAT positive (P=0.017). Follow-up of
      the BAT-positive patients showed a decrease over time, with 60% of these patients
      becoming negative after 6 months. CONCLUSIONS: BAT is a useful complement to skin
      testing for the evaluation of immediate allergic reactions to pyrazolones.
      Although not optimal, BAT sensitivity was also positive in patients with a
      negative skin test and it is a reasonable alternative in patients with severe
      reactions who may develop symptoms after skin testing. The time of performance of
      the test is critical to obtain a positive response.

PMID- 19400911
TI  - Influence of total serum IgE levels on the in vitro detection of beta-lactams
      specific IgE antibodies.
AB  - BACKGROUND: Allergic reactions to beta-lactams are a frequent cause of adverse
      drug reactions; the diagnosis is based on history, clinical examination, skin
      testing (prick and intradermal) and demonstration of serum-specific IgE
      antibodies (Abs). OBJECTIVE: We compared the diagnostic performance of the Phadia
      CAP system for the detection of IgE to beta-lactams carried out using the new
      test with cut-off limits of 0.10 kUA/L and the old test with cut-off limits of
      0.35 kUA/L for positive results; subsequently, we analysed the effect of total
      serum IgE values and of atopic phenotype on the diagnostic performance of the
      tests. METHODS: The study comprised a total of 34 patients with a history of
      immediate adverse reactions to beta-lactams, which were confirmed by positive
      skin testing, and 115 control subjects with tolerance to beta-lactams over the
      last year. The Phadia CAP System was used for the determination of serum total
      and specific IgE Abs towards penicilloyl G (c1), penicilloyl V (c2), ampicilloyl
      (c5) and amoxicilloyl (c6). The overall diagnostic performance was assessed as a
      diagnostic odds ratio (DOR). RESULTS: The new test showed a higher sensitivity
      (85% vs. 44%) than the old test and a lower specificity (54% vs. 80%) but the
      overall diagnostic performance was poor (DOR 6.78 vs. 3.16, P = 0.333) in both
      tests. The total IgE value influences the DOR of both tests; DOR was better for
      values under 200 kU/L [DOR = 66; 95% confidence interval (CI): 11.3-384.1] or 500
      kU/L (DOR = 45.7; 95% CI: 5.3-394.4) for the new and old tests, respectively.
      CONCLUSIONS: The reduction in the positive cut off value has not significantly
      improved the overall diagnostic performance of the beta-lactams-specific IgE
      assay. Because of the influence of serum total IgE on the detection of beta
      lactam-specific IgE Abs, the combination of both tests is mandatory in the in
      vitro diagnostic approach of beta-lactam allergy.

PMID- 19400912
TI  - Maternal smoking during pregnancy and offspring obesity: meta-analysis.
AB  - BACKGROUND: Recent reports have suggested that maternal smoking may increase the
      risk of development of obesity in the unborn child in later life, but relatively
      few cohort studies have been done on the relationship between maternal smoking
      during pregnancy and future development of metabolic syndrome. METHODS: A
      systematic review and meta-analysis of observational studies reporting effect
      estimates and 95% confidence intervals (95%CI) was conducted on the association
      between maternal smoking during pregnancy and obesity of future offspring.
      RESULTS: Seventeen papers were identified from 444 English-language papers (key
      word search: maternal smoking and obesity) in PubMed. All papers showed a
      positive association between maternal smoking during pregnancy and childhood
      obesity. The meta-analysis, using the DerSimonian-Laird method, found the
      association to be statistically significant. In association with maternal smoking
      during pregnancy and body mass index with more than 95%CI in the offspring aged 3
      33 years, the pooled odds ratio calculated from 16 of these 17 studies was 1.64
      (95%CI: 1.42-1.90). After adjustment for publication bias, the pooled adjusted
      odds ratio was 1.52 (95%CI: 1.36-1.70). In addition, confounders of maternal
      obesity, low social status, low birthweight and not being breast-fed seemed to be
      risk factors for offspring obesity. CONCLUSION: Maternal smoking during pregnancy
      may cause future obesity and metabolic syndrome.

PMID- 19400913
TI  - Prediction for developmental delay on Neonatal Oral Motor Assessment Scale in
      preterm infants without brain lesion.
AB  - BACKGROUND: Preterm infants often have difficulty in achieving a coordinated
      sucking pattern. To analyze the correlation between preterm infants with
      disorganized sucking and future development, weekly studies were performed of 27
      preterm infants from initiation of bottle feeding until a normal sucking pattern
      was recognized. METHODS: A total of 27 preterm infants without brain lesion
      participated in the present study. Neonatal Oral Motor Assessment Scale (NOMAS)
      was utilized to evaluate the sucking pattern. Infants who were initially assessed
      as having disorganized sucking on NOMAS and regained a normal sucking pattern by
      37 weeks old were assigned to group I; infants with a persistent disorganized
      sucking pattern after 37 weeks were assigned to group II. The mental (MDI) and
      psychomotor (PDI) developmental indices of Bayley Scales of Infant Development,
      second edition were used for follow-up tests to demonstrate neurodevelopment at 6
      months and 12 months of corrected age. RESULTS: At 6 months follow up, subjects
      in group I had a significantly higher PDI score than group II infants (P= 0.04).
      At 12 months follow up, group I subjects had a significantly higher score on MDI
      (P= 0.03) and PDI (P= 0.04). There was also a higher rate for development delay
      in group II at 6 months (P= 0.05). CONCLUSION: NOMAS-based assessment for
      neonatal feeding performance could be a helpful tool to predict
      neurodevelopmental outcome at 6 and 12 months. Close follow up and early
      intervention may be necessary for infants who present with a disorganized sucking
      pattern after 37 weeks post-conceptional age.

PMID- 19400925
TI  - Colonic movements in healthy subjects as monitored by a Magnet Tracking System.
AB  - The Magnet Tracking System (MTS) is a minimally-invasive technique of continuous
      evaluation of gastrointestinal motility. In this study, MTS was used to analyse
      colonic propulsive dynamics and compare the transit of a magnetic pill with that
      of standard radio-opaque markers. MTS monitors the progress in real time of a
      magnetic pill through the gut. Ten men and 10 women with regular daily bowel
      movements swallowed this pill and 10 radio-opaque markers at 8 pm. Five hours of
      recordings were conducted during 2 following mornings. Origin, direction,
      amplitude and velocity of movements were analysed relative to space-time plots of
      the pill trajectory. Abdominal radiographs were taken to compare the progress of
      both pill and markers. The magnetic pill lay idle for 90% of its sojourn in the
      colon; its total retrograde displacement accounted for only 20% of its overall
      movement. Analysis of these movements showed a bimodal distribution of
      velocities: around 1.5 and 50 cm min(-1), the latter being responsible for 2/3 of
      distance traversed. There were more movements overall and more mass movements in
      males. Net hourly forward progress was greater in the left than right colon, and
      greater in males. The position of the magnetic pill correlated well with the
      advancement of markers. MTS showed patterns and propulsion dynamics of colonic
      segments with as yet unmet precision. Detailed analysis of slow and fast patterns
      of colonic progress makes it possible to specify the motility of colonic
      segments, and any variability in gender. Such analysis opens up promising avenues
      in studies of motility disorders.

PMID- 19400926
TI  - Inhibition of cell death results in hyperganglionosis: implications for enteric
      nervous system development.
AB  - The enteric nervous system (ENS) is derived from vagal and sacral neural crest
      cells (NCC) that delaminate from the neural tube and undergo extensive migration
      and proliferation in order to colonize the entire length of the gut and
      differentiate into many millions of neurons and glial cells. Although apoptotic
      programmed cell death is an essential physiological process during development of
      the majority of the vertebrate nervous system, apoptosis within early ENS
      development has not been comprehensively investigated. The aim of this study was
      to determine the presence and extent of apoptosis within the vagal NCC population
      that gives rise to most of the ENS in the chick embryo. We demonstrated that
      apoptotic cells, as shown by terminal deoxynucleotidyl transferase biotin-dUTP
      nick end labelling and active caspase-3 immunoreactivity, are present within an
      electroporated green fluorescent protein (GFP) and human natural killer-1 (HNK-1)
      immunopositive NCC population migrating from the vagal region of the neural tube
      to the developing foregut. Inhibition of caspase activity in vagal NCC, by
      electroporation with a dominant-negative form of caspase-9, increased the number
      of vagal NCC available for ENS formation, as shown by 3-dimensional
      reconstruction of serial GFP or HNK-1 labelled sections, and resulted in
      hyperganglionosis within the proximal foregut, as shown by NADPH-diaphorase whole
      gut staining. These findings suggest that apoptotic cell death may be a normal
      process within the precursor pool of pre-enteric NCC that migrates to the gut,
      and as such it may play a role in the control of ENS formation.

PMID- 19400927
TI  - Abstracts of the 23rd European Immunogenetics and Histocompatibility Conference.
      Ulm, Germany. May 9-12, 2009.

PMID- 19400928
TI  - Gene expression profile of bladder tissue of patients with ulcerative
      interstitial cystitis.
AB  - BACKGROUND: Interstitial cystitis (IC), a chronic bladder disease with an
      increasing incidence, is diagnosed using subjective symptoms in combination with
      cystoscopic and histological evidence. By cystoscopic examination, IC can be
      classified into an ulcerative and a non-ulcerative subtype. To better understand
      this debilitating disease on a molecular level, a comparative gene expression
      profile of bladder biopsies from patients with ulcerative IC and control patients
      has been performed. RESULTS: Gene expression profiles from bladder biopsies of
      five patients with ulcerative IC and six control patients were generated using
      Affymetrix GeneChip expression arrays (Affymetrix--GeneChip Human Genome U133
      Plus 2.0). More than 31,000 of > 54,000 tested probe sets were present (detection
      p-value < 0.05). The difference between the two groups was significant for over
      3,500 signals (t-test p-value < 0.01), and approximately 2,000 of the signals
      (corresponding to approximately 1,000 genes) showed an IC-to-healthy expression
      ratio greater than two. The IC pattern had similarities to patterns from immune
      system, lymphatic, and autoimmune diseases. The dominant biological processes
      were the immune and inflammatory responses. Many of the up-regulated genes were
      expressed in leukocytes, suggesting that leukocyte invasion into the bladder wall
      is a dominant feature of ulcerative IC. Histopathological data supported these
      findings. CONCLUSION: GeneChip expression arrays present a global picture of
      ulcerative IC and provide us with a series of marker genes characteristic for
      this subtype of the disease. Evaluation of biopsies from other bladder patients
      with similar symptoms (e.g. patients with non-ulcerative IC) will further
      indicate whether the data presented here will be valuable for the diagnosis of
      IC.

PMID- 19400929
TI  - Adherence to anti-retroviral therapy among HIV patients in Bangalore, India.
AB  - INTRODUCTION: Human Immunodeficiency Virus (HIV) has an estimated prevalence of
      0.9% in India (5.2 million). Anti-retroviral drugs (ARV) are the treatments of
      choice and non-adherence is an important factor in treatment failure and
      development of resistance, as well as being a powerful predictor of survival.
      This study assesses adherence to ARV in HIV positive patients in Bangalore,
      India, a country where only 10% of those who need therapy are receiving it.
      METHODS: A cross-sectional anonymous questionnaire survey of 60 HIV antibody
      positive patients was carried out with patients attending HIV outpatient services
      at two centres: The Chest and Maternity Centre, Rajajinagar, and Wockhardt
      Hospital and Heart Institute, Bangalore. Consent was obtained. Translation was
      done by a translator and doctors where required. Data was analysed using SPSS
      statistical analysis. RESULTS: A response rate of 88% (53/60) was achieved. The
      mean patient age was 39.98 years, with 50% aged 30-40, and 73.6% of participants
      being male. Mean family size was 4.8 (1-13). 21% lived less than 50 kms and 21%
      greater than 400 kms from clinic.60% reported they were fully adherent. Adherence
      was statistically significantly linked to regular follow-up attendance (70.5%, p
      = 0.002). No other results were statistically significant but trends were found.
      "100% adherence" trends were seen in older patients, male gender, those from
      larger families, those who had a previous AIDS defining illness, those taking
      fewer tablets, and without food restrictions. Commonest side-effects causing non
      adherence were metabolic reasons (66%) and GI symptoms (50%). No trends were seen
      for education level, family income, distance travelled to clinic, time since
      diagnosis, or time on ART. CONCLUSION: Regular attendance for follow up was
      statistically significant for 100% lifetime adherence. Positive trends were seen
      in those in larger families, older, those who had AIDS defining illness, simple
      regimes, and without side-effects. Education, income, distance travelled and
      length of time diagnosed or treated had no effect on adherence.

PMID- 19400930
TI  - Induction of mast cell accumulation, histamine release and skin edema by N49
      phospholipase A2.
AB  - BACKGROUND: It has been recognized that phospholipase A2 (PLA2) is a crucial
      component of snake venom, which contributes greatly to snake venom induced
      inflammation in man. However, the mechanisms through which N49 PLA2 provoke
      inflammation remain unclear. Recently, a N49 PLA2, TM-N49 from Protobothrops
      mucrosquamatus crude venom was characterized in our laboratory. Since the
      purification procedure developed is able to supply us with relatively large
      quantity of highly purified TM-N49, we investigated the ability of TM-N49 in
      induction of inflammation. RESULTS: The results showed that TM-N49 provoked a
      dose dependent increase in microvascular leakage in the skin of rats. The potency
      of TM-N49 in induction of skin edema appeared similar potency of bradykinin and
      histamine. Pretreatment of rats with compound 48/80 diminished TM-N49 induced
      skin reaction and reduced mast cell numbers in rats. Ginkgolide B and
      cyproheptadine, but not terfenadine and quinacrine, inhibited TM-N49 elicited
      microvascular leakage when they were co-injected with the stimulus to rat skin.
      Moreover, TM-N49 was found to induce histamine release from human colon, lung and
      tonsil mast cells, and both metabolic inhibitors and pertussis toxin were capable
      of inhibiting TM-N49 elicited histamine release. TM-N49 induced mast cell
      accumulation in the peritoneum of mice, which was inhibited by co-injection of
      ginkgolide B, cyproheptadine and terfenadine. Intravenous injection of monoclonal
      antibodies against CD18, ICAM-1 and CD11a also blocked TM-N49 induced mast cell
      accumulation. CONCLUSION: TM-N49 is a potent stimulus for skin edema, mast cell
      activation and accumulation.

PMID- 19400932
TI  - Contextual adaptation of the Personnel Evaluation Standards for assessing faculty
      evaluation systems in developing countries: the case of Iran.
AB  - BACKGROUND: Faculty evaluations can identify needs to be addressed in effective
      development programs. Generic evaluation models exist, but these require
      adaptation to a particular context of interest. We report on one approach to such
      adaptation in the context of medical education in Iran, which is integrated into
      the delivery and management of healthcare services nationwide. METHODS: Using a
      triangulation design, interviews with senior faculty leaders were conducted to
      identify relevant areas for faculty evaluation. We then adapted the published
      checklist of the Personnel Evaluation Standards to fit the Iranian medical
      universities' context by considering faculty members' diverse roles. Then the
      adapted instrument was administered to faculty at twelve medical schools in Iran.
      RESULTS: The interviews revealed poor linkages between existing forms of
      development and evaluation, imbalance between the faculty work components and
      evaluated areas, inappropriate feedback and use of information in decision
      making. The principles of Personnel Evaluation Standards addressed almost all of
      these concerns and were used to assess the existing faculty evaluation system and
      also adapted to evaluate the core faculty roles. The survey response rate was
      74%. Responses showed that the four principles in all faculty members' roles were
      met occasionally to frequently. Evaluation of teaching and research had the
      highest mean scores, while clinical and healthcare services, institutional
      administration, and self-development had the lowest mean scores. There were
      statistically significant differences between small medium and large medical
      schools (p < 0.000). CONCLUSION: The adapted Personnel Evaluation Standards
      appears to be valid and applicable for monitoring and continuous improvement of a
      faculty evaluation system in the context of medical universities in Iran. The
      approach developed here provides a more balanced assessment of multiple faculty
      roles, including educational, clinical and healthcare services. In order to
      address identified deficiencies, the evaluation system should recognize,
      document, and uniformly reward those activities that are vital to the academic
      mission. Inclusion of personal developmental concerns in the evaluation
      discussion is essential for evaluation systems.

PMID- 19400931
TI  - Admission C-reactive protein after acute ischemic stroke is associated with
      stroke severity and mortality: the 'Bergen stroke study'.
AB  - BACKGROUND: There is growing evidence that inflammation plays an important role
      in atherogenesis. Previous studies show that C-reactive protein (CRP), an
      inflammatory marker, is associated with stroke outcomes and future vascular
      events. It is not clear whether this is due a direct dose-response effect or
      rather an epiphenomenon. We studied the effect of CRP measured within 24 hours
      after stroke onset on functional outcome, mortality and future vascular events.
      METHODS: We prospectively studied 498 patients with ischemic stroke who were
      admitted within 24 hours after the onset of symptoms. CRP and NIH stroke scale
      (NIHSS) were measured at the time of admission. Short-term functional outcome was
      measured by modified Rankin scale (mRS) and Barthel ADL index (BI) 7 days after
      admission. Patients were followed for up to 2.5 years for long-term mortality and
      future vascular events data. RESULTS: The median CRP at admission was 3 mg/L.
      High CRP was associated with high NIHSS (p = 0.01) and high long-term mortality
      (p < 0.0001). After adjusting for confounding variables, high CRP remained to be
      associated with high NIHSS (p = 0.02) and high long-term mortality (p = 0.002).
      High CRP was associated with poor short-term functional outcomes (mRS > 3; BI <
      95) (p = 0.01; p = 0.03). However, the association was not significant after
      adjusting for confounding variables including stroke severity (p = 0.98; p =
      0.88). High CRP was not associated with future vascular events (p = 0.98).
      CONCLUSION: Admission CRP is associated with stroke severity and long-term
      mortality when measured at least 24 hours after onset. There is a crude
      association between high CRP and short-term functional outcome which is likely
      secondary to stroke severity. CRP is an independent predictor of long-term
      mortality after ischemic stroke.

PMID- 19400933
TI  - Pattern of benzodiazepine use in psychiatric outpatients in Pakistan: a cross
      sectional survey.
AB  - BACKGROUND: Benzodiazepines (BDZ) are the largest-selling drug group in the
      world. The potential of dependence with BDZ has been known for almost three
      decades now. In countries like Pakistan where laws against unlicensed sale of BDZ
      are not implemented vigorously the risk of misuse of and dependence on these
      drugs is even higher. Previous studies have shown that BDZ prevalence among
      patients/visitors to general outpatient clinics in Pakistan may be as high as
      30%. However, no research has been carried out on the prevalence of BDZ use in
      psychiatric patients in Pakistan. METHODS: We carried out a cross-sectional
      survey over 3 months in psychiatry outpatient clinics of two tertiary care
      hospitals in Karachi and Lahore. Besides basic socio-demographic data the
      participants were asked if they were taking a BDZ at present and if yes, the
      frequency, route and dosage of the drug, who had initiated the drug and why it
      had been prescribed. We used chi-square test and t-test to find out which socio
      demographic or clinical factors were associated with an increased risk of BDZ
      use. We used Logistic Regression to find out which variable(s) best predicted the
      increased likelihood of BDZ use. RESULTS: Out of a total of 419 participants 187
      (45%) of the participants had been currently using at least one BDZ. Seventy
      three percent of the users had been using the drug for 4 weeks or longer and 87%
      were taking it every day. In 90% of cases the BDZ had been initiated by a doctor,
      who was a psychiatrist in 70% of the cases. Female gender, increasing age, living
      in Lahore, and having seen a psychiatrist before, were associated with an
      increased likelihood of using BDZ. CONCLUSION: The study shows how high BDZ use
      is in psychiatric outpatients in Pakistan. Most of the users were taking it for a
      duration and with a frequency which puts them at risk of becoming dependent on
      BDZ. In most of the cases it had been initiated by a doctor. Both patients and
      doctors need to be made aware of the risk of dependence associated with the use
      of BDZ.

PMID- 19400934
TI  - Long-term recurrence and complication rates after incisional hernia repair with
      the open onlay technique.
AB  - BACKGROUND: Incisional hernia after abdominal surgery is a well-known
      complication. Controversy still exists with respect to the choice of hernia
      repair technique. The objective of this study was to evaluate the long-term
      recurrence rate as well as surgical complications in a consecutive group of
      patients undergoing open repair using an onlay mesh technique. METHODS:
      Consecutive patients undergoing open incisional hernia repair with onlay
      technique between 01/05/1995 and 01/09/2007 at a single institution were included
      in the study. For follow-up patients were contacted by telephone, and answered a
      questionnaire containing questions related to the primary operation, the hernia
      and general risk factors. Patients were examined by a consultant surgeon in the
      outpatient clinic or in the patient's home if there was suspicion of an
      incisional hernia recurrence. RESULTS: The study included 56 patients with 100%
      follow-up. The median follow-up was 35 months (range 4-151). Recurrent incisional
      hernia was found in 8 of 56 patients (15%, 95% CI: 6-24). The overall
      complication rate was 13% (95% CI, 4-22). All complications were minor and needed
      no hospital admission. CONCLUSION: This study with a long follow-up showed low
      recurrence and complication rates in patients undergoing incisional hernia repair
      with the open onlay technique.

PMID- 19400935
TI  - Treatment of multicentric Castleman's Disease accompanying multiple myeloma with
      bortezomib: a case report.
AB  - Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder of
      unknown etiology and characterized by various clinical manifestations and
      multiple organ involvement. It has been reported in association with POEMS
      syndrome and can progress to Kaposi's sarcoma or malignant lymphoma. The disease
      runs a more aggressive course and a poor prognosis. Optimal therapies have not
      been well established up to now. We here reported a case of rare MCD complicated
      with multiple myeloma who received bortezomib and achieved very good remission.
      To our knowledge, this is the first report on MCD in the setting of multiple
      myeloma with good response to bortezomib.

PMID- 19400936
TI  - Origin and evolution of the RIG-I like RNA helicase gene family.
AB  - BACKGROUND: The DExD/H domain containing RNA helicases such as retinoic acid
      inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5)
      are key cytosolic pattern recognition receptors (PRRs) for detecting nucleotide
      pathogen associated molecular patterns (PAMPs) of invading viruses. The RIG-I and
      MDA5 proteins differentially recognise conserved PAMPs in double stranded or
      single stranded viral RNA molecules, leading to activation of the interferon
      system in vertebrates. They share three core protein domains including a RNA
      helicase domain near the C terminus (HELICc), one or more caspase activation and
      recruitment domains (CARDs) and an ATP dependent DExD/H domain. The RIG-I/MDA5
      directed interferon response is negatively regulated by laboratory of genetics
      and physiology 2 (LGP2) and is believed to be controlled by the mitochondria
      antiviral signalling protein (MAVS), a CARD containing protein associated with
      mitochondria. RESULTS: The DExD/H containing RNA helicases including RIG-I, MDA5
      and LGP2 were analysed in silico in a wide spectrum of invertebrate and
      vertebrate genomes. The gene synteny of MDA5 and LGP2 is well conserved among
      vertebrates whilst conservation of the gene synteny of RIG-I is less apparent.
      Invertebrate homologues had a closer phylogenetic relationship with the
      vertebrate RIG-Is than the MDA5/LGP2 molecules, suggesting the RIG-I homologues
      may have emerged earlier in evolution, possibly prior to the appearance of
      vertebrates. Our data suggest that the RIG-I like helicases possibly originated
      from three distinct genes coding for the core domains including the HELICc, CARD
      and ATP dependent DExD/H domains through gene fusion and gene/domain duplication.
      Furthermore, presence of domains similar to a prokaryotic DNA restriction enzyme
      III domain (Res III), and a zinc finger domain of transcription factor (TF) IIS
      have been detected by bioinformatic analysis. CONCLUSION: The RIG-I/MDA5 viral
      surveillance system is conserved in vertebrates. The RIG-I like helicase family
      appears to have evolved from a common ancestor that originated from genes
      encoding different core functional domains. Diversification of core functional
      domains might be fundamental to their functional divergence in terms of
      recognition of different viral PAMPs.

PMID- 19400937
TI  - NuMA is required for proper spindle assembly and chromosome alignment in
      prometaphase.
AB  - BACKGROUND: NuMA is a protein that has been previously shown to play a role in
      focusing microtubules at the mitotic spindle poles. However, most previous work
      relies on experimental methods that might cause dominant side effects on spindle
      formation, such as microinjection of antibodies, overexpression of mutant
      protein, or immunodepletion of NuMA-containing protein complexes. FINDINGS: To
      circumvent these technical problems, we performed siRNA experiments in which we
      depleted the majority of NuMA in human cultured cells. Depleted mitotic cells
      show a prolonged duration of prometaphase, with spindle pole defects and with
      unattached, unaligned chromosomes. CONCLUSION: Our data confirm that NuMA is
      important for spindle pole formation, and for cohesion of centrosome-derived
      microtubules with the bulk of spindle microtubules. Our findings of NuMA
      dependent defects in chromosome alignment suggest that NuMA is involved in
      stabilizing kinetochore fibres.

PMID- 19400938
TI  - Oncologist use of the Adjuvant! model for risk communication: a pilot study
      examining patient knowledge of 10-year prognosis.
AB  - BACKGROUND: Our purpose was to collect preliminary data on newly diagnosed breast
      cancer patient knowledge of prognosis before and after oncology visits. Many
      oncologists use a validated prognostic software model, Adjuvant!, to estimate 10
      year recurrence and mortality outcomes for breast cancer local and adjuvant
      therapy. Some oncologists are printing Adjuvant! screens to use as visual aids
      during consultations. No study has reported how such use of Adjuvant! printouts
      affects patient knowledge of prognosis. We hypothesized that Adjuvant! printouts
      would be associated with significant changes in the proportion of patients with
      accurate understanding of local therapy prognosis. METHODS: We recruited a
      convenience sample of 20 patients seen by 2 senior oncologists using Adjuvant!
      printouts of recurrence and mortality screens in our academic medical center. We
      asked patients for their estimates of local therapy recurrence and mortality
      risks and counted the number of patients whose estimates were within +/- 5% of
      Adjuvant! before and after the oncology visit, testing whether pre/post changes
      were significant using McNemar's two-sided test at a significance level of 5%.
      RESULTS: Two patients (10%) accurately estimated local therapy recurrence and
      mortality risks before the oncology visit, while seven out of twenty (35%) were
      accurate afterwards (p = 0.125). CONCLUSION: A majority of patients in our sample
      were inaccurate in estimating their local therapy recurrence and mortality risks,
      even after being shown printouts summarizing these risks during their oncology
      visits. Larger studies are needed to replicate or repudiate these preliminary
      findings, and test alternative methods of presenting risk estimates. Meanwhile,
      oncologists should be wary of relying exclusively on Adjuvant! printouts to
      communicate local therapy recurrence and mortality estimates to patients, as they
      may leave a majority of patients misinformed.

PMID- 19400939
TI  - Household catastrophic health expenditure: evidence from Georgia and its policy
      implications.
AB  - BACKGROUND: To quantify extent of catastrophic household health expenditures,
      determine factors influencing it and estimate Fairness in Financial Contribution
      (FFC) index in Georgia to establish the baseline for expected reforms and
      contribute to the design and fine-tuning of the major reforms in health care
      financing initiated by the government mid-2007. METHODS: The research is based on
      the nationally representative Health Care Utilization and Expenditure survey
      conducted during May-June 2007, prior to preparing for new phase of
      implementation for the health care financing reforms. Households' catastrophic
      health expenditures were estimated according to the methodology proposed by WHO-
      Ke Xu. A logistic regression (logit) model was used to predict probability of
      catastrophic health expenditure occurrence. RESULTS: In Georgia between 2000 and
      2007 access to care for poor has improved slightly and the share of households
      facing catastrophic health expenditures have seemingly increased from 2.8% in
      1999 to 11.7% in 2007. However, this variance may be associated with the
      methodological differences of the respective surveys from which the analysis were
      derived. The high level of the catastrophic health expenditure may be associated
      with the low share of prepayment in national health expenditure, adequate
      availability of services and a high level of poverty in the country. Major
      factors determining the financial catastrophe related to ill health were
      hospitalization, household members with chronic illness and poverty status of the
      household. The FFC for Georgia appears to have improved since 2004. CONCLUSION:
      Reducing the prevalence of catastrophic health expenditure is a policy objective
      of the government, which can be achieved by focusing on increased financial
      protection offered to poor and expanding government financed benefits for poor
      and chronically ill by including and expanding inpatient coverage and adding drug
      benefits. This policy recommendation may also be relevant for other Low and
      Middle Income countries with similar levels of out of pocket payments and
      catastrophic health expenditures.

PMID- 19400940
TI  - A combinatorial approach to determine the context-dependent role in
      transcriptional and posttranscriptional regulation in Arabidopsis thaliana.
AB  - BACKGROUND: While progresses have been made in mapping transcriptional regulatory
      networks, posttranscriptional regulatory roles just begin to be uncovered, which
      has arrested much attention due to the discovery of miRNAs. Here we demonstrated
      a combinatorial approach to incorporate transcriptional and posttranscriptional
      regulatory sequences with gene expression profiles to determine their
      probabilistic dependencies. RESULTS: We applied the proposed method to microarray
      time course gene expression profiles and could correctly predict expression
      patterns for more than 50% of 1,132 genes, based on the sequence motifs adopted
      in the network models, which was statistically significant. Our study suggested
      that the contribution of miRNA regulation towards gene expression in plants may
      be more restricted than that of transcription factors; however, miRNAs might
      confer additional layers of robustness on gene regulation networks. The programs
      written in C++ and PERL implementing methods in this work are available for
      download from our supplemental data web page. CONCLUSION: In this study we
      demonstrated a combinatorial approach to incorporate miRNA target motifs (miRNA
      mediated posttranscriptional regulatory sites) and TFBSs (transcription factor
      binding sites) with gene expression profiles to reconstruct the regulatory
      networks. The proposed approach may facilitate the incorporation of diverse
      sources with limited prior knowledge.

PMID- 19400941
TI  - A translational framework for public health research.
AB  - BACKGROUND: The paradigm of translational medicine that underpins frameworks such
      as the Cooksey report on the funding of health research does not adequately
      reflect the complex reality of the public health environment. We therefore
      outline a translational framework for public health research. DISCUSSION: Our
      framework redefines the objective of translation from that of institutionalising
      effective interventions to that of improving population health by influencing
      both individual and collective determinants of health. It incorporates
      epidemiological perspectives with those of the social sciences, recognising that
      many types of research may contribute to the shaping of policy, practice and
      future research. It also identifies a pivotal role for evidence synthesis and the
      importance of non-linear and intersectoral interfaces with the public realm.
      SUMMARY: We propose a research agenda to advance the field and argue that
      resources for 'applied' or 'translational' public health research should be
      deployed across the framework, not reserved for 'dissemination' or
      'implementation'.

PMID- 19400942
TI  - Src, PKCalpha, and PKCdelta are required for alphavbeta3 integrin-mediated
      metastatic melanoma invasion.
AB  - BACKGROUND: Integrins, cell-surface receptors that mediate adhesive interactions
      between cells and the extracellular matrix (ECM), play an important role in
      cancer progression. Expression of the vitronectin receptor alphavbeta3 integrin
      correlates with increased invasive and metastatic capacity of malignant
      melanomas, yet it remains unclear how expression of this integrin triggers
      melanoma invasion and metastasis. RESULTS: Two melanoma cell lines C8161.9 and
      M14 both express high levels of alphavbeta3 integrin and adhere to vitronectin.
      However, only the highly metastatic C8161.9 cells are capable of invading
      vitronectin-enriched Matrigel in an alphavbeta3-depenent manner. Elevated levels
      of PKCalpha and PKCdelta, and activated Src were detected specifically in the
      highly metastatic melanoma cells, but not in the low metastatic M14 cells.
      Inhibition of Src or PKC activity suppressed alphavbeta3-dependent invasion.
      Furthermore, over expression of Src or PKCalpha and PKCdelta was sufficient to
      confer alphavbeta3-dependent invasiveness to M14 cells. Stress fiber formation
      and focal adhesion formation were almost completely absent in C8161.9 cells
      compared to M14 cells. Inhibition of Src signaling was sufficient to restore
      normal actin architecture, and resulted in decreased p190RhoGAP phosphorylation
      and enhanced RhoA activity. Src had no effect on Rac activity. Loss of PKCalpha
      expression, but not PKCdelta, by siRNA inhibited Rac and PAK activity as well as
      invasiveness. Loss of PKCalpha restored focal adhesion formation and partially
      restored stress fiber formation, while loss of PKCdelta primarily restored stress
      fibers. CONCLUSION: The misregulated expression of PKCalpha and PKCdelta and
      elevated Src activity in metastatic melanoma cells is required for efficient
      alphavbeta3-mediated invasion. PKCalpha and Src enhance alphavbeta3-mediated
      invasion in part by increasing the GTPase activity of Rac relative to RhoA.
      PKCalpha influences focal adhesion formation, while PKCdelta controls stress
      fibers.

PMID- 19400943
TI  - Absence of knockdown resistance suggests metabolic resistance in the main malaria
      vectors of the Mekong region.
AB  - BACKGROUND: As insecticide resistance may jeopardize the successful malaria
      control programmes in the Mekong region, a large investigation was previously
      conducted in the Mekong countries to assess the susceptibility of the main
      malaria vectors against DDT and pyrethroid insecticides. It showed that the main
      vector, Anopheles epiroticus, was highly pyrethroid-resistant in the Mekong
      delta, whereas Anopheles minimus sensu lato was pyrethroid-resistant in northern
      Vietnam. Anopheles dirus sensu stricto showed possible resistance to type II
      pyrethroids in central Vietnam. Anopheles subpictus was DDT- and pyrethroid
      resistant in the Mekong Delta. The present study intends to explore the
      resistance mechanisms involved. METHODS: By use of molecular assays and
      biochemical assays the presence of the two major insecticide resistance
      mechanisms, knockdown and metabolic resistance, were assessed in the main malaria
      vectors of the Mekong region. RESULTS: Two FRET/MCA assays and one PCR-RFLP were
      developed to screen a large number of Anopheles populations from the Mekong
      region for the presence of knockdown resistance (kdr), but no kdr mutation was
      observed in any of the study species. Biochemical assays suggest an esterase
      mediated pyrethroid detoxification in An. epiroticus and An. subpictus of the
      Mekong delta. The DDT resistance in An. subpictus might be conferred to a high
      GST activity. The pyrethroid resistance in An. minimus s.l. is possibly
      associated with increased detoxification by esterases and P450 monooxygenases.
      CONCLUSION: As different metabolic enzyme systems might be responsible for the
      pyrethroid and DDT resistance in the main vectors, each species may have a
      different response to alternative insecticides, which might complicate the
      malaria vector control in the Mekong region.

PMID- 19400944
TI  - The multiplex bead array approach to identifying serum biomarkers associated with
      breast cancer.
AB  - INTRODUCTION: Breast cancer is the most common type of cancer seen in women in
      western countries. Thus, diagnostic modalities sensitive to early-stage breast
      cancer are needed. Antibody-based array platforms of a data-driven type, which
      are expected to facilitate more rapid and sensitive detection of novel
      biomarkers, have emerged as a direct, rapid means for profiling cancer-specific
      signatures using small samples. In line with this concept, our group constructed
      an antibody bead array panel for 35 analytes that were selected during the
      discovery step. This study was aimed at testing the performance of this 35-plex
      array panel in profiling signatures specific for primary non-metastatic breast
      cancer and validating its diagnostic utility in this independent population.
      METHODS: Thirty-five analytes were selected from more than 50 markers through
      screening steps using a serum bank consisting of 4,500 samples from various types
      of cancer. An antibody-bead array of 35 markers was constructed using the Luminex
      bead array platform. A study population consisting of 98 breast cancer patients
      and 96 normal subjects was analysed using this panel. Multivariate classification
      algorithms were used to find discriminating biomarkers and validated with another
      independent population of 90 breast cancer and 79 healthy controls. RESULTS:
      Serum concentrations of epidermal growth factor, soluble CD40-ligand and
      proapolipoprotein A1 were increased in breast cancer patients. High-molecular
      weight-kininogen, apolipoprotein A1, soluble vascular cell adhesion molecule-1,
      plasminogen activator inhibitor-1, vitamin-D binding protein and vitronectin were
      decreased in the cancer group. Multivariate classification algorithms
      distinguished breast cancer patients from the normal population with high
      accuracy (91.8% with random forest, 91.5% with support vector machine, 87.6% with
      linear discriminant analysis). Combinatorial markers also detected breast cancer
      at an early stage with greater sensitivity. CONCLUSIONS: The current study
      demonstrated the usefulness of the antibody-bead array approach in finding
      signatures specific for primary non-metastatic breast cancer and illustrated the
      potential for early, high sensitivity detection of breast cancer. Further
      validation is required before array-based technology is used routinely for early
      detection of breast cancer.

PMID- 19400946
TI  - Membrane estrogen receptor-alpha-mediated nongenomic actions of phytoestrogens in
      GH3/B6/F10 pituitary tumor cells.
AB  - BACKGROUND: Estradiol (E2) mediates various intracellular signaling cascades from
      the plasma membrane via several estrogen receptors (ERs). The pituitary is an
      estrogen-responsive tissue, and we have previously reported that E2 can activate
      mitogen-activated protein kinases (MAPKs) such as ERK1/2 and JNK1/2/3 in the
      membrane ERalpha (mERalpha)-enriched GH3/B6/F10 rat pituitary tumor cell line.
      Phytoestrogens are compounds found in plants and foods such as soybeans, alfalfa
      sprouts, and red grapes. They are structurally similar to E2 and share a similar
      mechanism of action through their binding to ERs. Phytoestrogens bind to nuclear
      ERs with a much lower affinity and therefore are less potent in mediating genomic
      responses. However, little is known about their ability to act via mERs to
      mediate nongenomic effects. METHODS: To investigate the activation of different
      nongenomic pathways, and determine the involvement of mERalpha, we measured
      prolactin (PRL) release by radio-immunoassay, MAPK activations (ERK1/2 and
      JNK1/2/3) via a quantitative plate immunoassay, and intracellular [Ca2+] by Fura
      2 fluorescence imaging in cells treated with E2 or four different phytoestrogens
      (coumestrol, daidzein, genistein, and trans-resveratrol). RESULTS: Coumesterol
      and daidzein increased PRL release similar to E2 in GH3/B6/F10 cells, while
      genistein and trans-resveratrol had no effect. All of these compounds except
      genistein activated ERK1/2 signaling at 1-10 picomolar concentrations; JNK 1/2/3
      was activated by all compounds at a 100 nanomolar concentration. All compounds
      also caused rapid Ca2+ uptake, though in unique dose-dependent Ca2+ response
      patterns for several aspects of this response. A subclone of GH3 cells expressing
      low levels of mERalpha (GH3/B6/D9) did not respond to any phytoestrogen
      treatments for any of these responses, suggesting that these nongenomic effects
      were mediated via mERalpha. CONCLUSION: Phytoestrogens were much more potent in
      mediating these nongenomic responses (activation of MAPKs, PRL release, and
      increased intracellular [Ca2+]) via mERalpha than was previously reported for
      genomic responses. The unique non-monotonic dose responses and variant signaling
      patterns caused by E2 and all tested phytoestrogens suggest that complex and
      multiple signaling pathways or binding partners could be involved. By activating
      these different nongenomic signaling pathways, phytoestrogens could have
      significant physiological consequences for pituitary cell functions.

PMID- 19400945
TI  - Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation
      model.
AB  - BACKGROUND: Aberrant regulation of cell migration drives progression of many
      diseases, including cancer cell invasion and metastasis formation. Analysis of
      tumour invasion and metastasis in living organisms to date is cumbersome and
      involves difficult and time consuming investigative techniques. For primary human
      tumours we establish here a simple, fast, sensitive and cost-effective in vivo
      model to analyse tumour invasion and metastatic behaviour. METHODS: We
      fluorescently labelled small explants from gastrointestinal human tumours and
      investigated their metastatic behaviour after transplantation into zebrafish
      embryos and larvae. The transparency of the zebrafish embryos allows to follow
      invasion, migration and micrometastasis formation in real-time. High resolution
      imaging was achieved through laser scanning confocal microscopy of live
      zebrafish. RESULTS: In the transparent zebrafish embryos invasion, circulation of
      tumour cells in blood vessels, migration and micrometastasis formation can be
      followed in real-time. Xenografts of primary human tumours showed invasiveness
      and micrometastasis formation within 24 hours after transplantation, which was
      absent when non-tumour tissue was implanted. Furthermore, primary human tumour
      cells, when organotopically implanted in the zebrafish liver, demonstrated
      invasiveness and metastatic behaviour, whereas primary control cells remained in
      the liver. Pancreatic tumour cells showed no metastatic behaviour when injected
      into cloche mutant embryos, which lack a functional vasculature. CONCLUSION: Our
      results show that the zebrafish is a useful in vivo animal model for rapid
      analysis of invasion and metastatic behaviour of primary human tumour specimen.

PMID- 19400947
TI  - Unraveling the disease pathogenesis behind lethal hydrolethalus syndrome revealed
      multiple changes in molecular and cellular level.
AB  - BACKGROUND: Hydrolethalus syndrome (HLS) is a severe fetal malformation syndrome
      characterized by multiple developmental anomalies, including central nervous
      system (CNS) malformation such as hydrocephaly and absent midline structures of
      the brain, micrognathia, defective lobation of the lungs and polydactyly.
      Microscopically, immature cerebral cortex, abnormalities in radial glial cells
      and hypothalamic hamartoma are among key findings in the CNS of HLS fetuses. HLS
      is caused by a substitution of aspartic acid by glycine in the HYLS1 protein,
      whose function was previously unknown. RESULTS: To provide insight into the
      disease mechanism(s) of this lethal disorder we have studied different aspects of
      HLS and HYLS1. A genome-wide gene expression analysis indicated several
      upregulated genes in cell cycle regulatory cascades and in specific signal
      transduction pathways while many downregulated genes were associated with lipid
      metabolism. These changes were supported by findings in functional cell biology
      studies, which revealed an increased cell cycle rate and a decreased amount of
      apoptosis in HLS neuronal progenitor cells. Also, changes in lipid metabolism
      gene expression were reflected by a significant increase in the cholesterol
      levels of HLS liver tissues. In addition, based on our functional studies of
      HYLS1, we propose that HYLS1 is a transcriptional regulator that shuffles between
      the cytoplasm and the nucleus, and that when HYLS1 is mutated its function is
      significantly altered. CONCLUSION: In this study, we have shown that the HYLS1
      mutation has significant consequences in the cellular and tissue levels in HLS
      fetuses. Based on these results, it can be suggested that HYLS1 is part of the
      cellular transcriptional regulatory machinery and that the genetic defect has a
      widespread effect during embryonic and fetal development. These findings add a
      significant amount of new information to the pathogenesis of HLS and strongly
      suggest an essential role for HYLS1 in normal fetal development.

PMID- 19400948
TI  - Genome wide expression analysis of CBS domain containing proteins in Arabidopsis
      thaliana (L.) Heynh and Oryza sativa L. reveals their developmental and stress
      regulation.
AB  - BACKGROUND: In Arabidopsis thaliana (L.) Heynh and Oryza sativa L., a large
      number of genes encode proteins of unknown functions, whose characterization
      still remains one of the major challenges. With an aim to characterize these
      unknown proteins having defined features (PDFs) in plants, we have chosen to work
      on proteins having a cystathionine beta-synthase (CBS) domain. CBS domain as such
      has no defined function(s) but plays a regulatory role for many enzymes and thus
      helps in maintaining the intracellular redox balance. Its function as sensor of
      cellular energy has also been widely suggested. RESULTS: Our analysis has
      identified 34 CBS domain containing proteins (CDCPs) in Arabidopsis and 59 in
      Oryza. In most of these proteins, CBS domain coexists with other functional
      domain(s), which may indicate towards their probable functions. In order to
      investigate the role(s) of these CDCPs, we have carried out their detailed
      analysis in whole genomes of Arabidopsis and Oryza, including their
      classification, nomenclature, sequence analysis, domain analysis, chromosomal
      locations, phylogenetic relationships and their expression patterns using public
      databases (MPSS database and microarray data). We have found that the transcript
      levels of some members of this family are altered in response to various stresses
      such as salinity, drought, cold, high temperature, UV, wounding and genotoxic
      stress, in both root and shoot tissues. This data would be helpful in exploring
      the so far obscure functions of CBS domain and CBS domain-containing proteins in
      plant stress responses. CONCLUSION: We have identified, classified and suggested
      the nomenclature of CDCPs in Arabidopsis and Oryza. A comprehensive analysis of
      expression patterns for CDCPs using the already existing transcriptome profiles
      and MPSS database reveals that a few CDCPs may have an important role in stress
      response/tolerance and development in plants, which needs to be validated further
      through functional genomics.

PMID- 19400949
TI  - DIRS1-like retrotransposons are widely distributed among Decapoda and are
      particularly present in hydrothermal vent organisms.
AB  - BACKGROUND: Transposable elements are major constituents of eukaryote genomes and
      have a great impact on genome structure and stability. Considering their
      mutational abilities, TEs can contribute to the genetic diversity and evolution
      of organisms. Knowledge of their distribution among several genomes is an
      essential condition to study their dynamics and to better understand their role
      in species evolution. DIRS1-like retrotransposons are a particular group of
      retrotransposons according to their mode of transposition that implies a tyrosine
      recombinase. To date, they have been described in a restricted number of species
      in comparison with the LTR retrotransposons. In this paper, we determine the
      distribution of DIRS1-like elements among 25 decapod species, 10 of them living
      in hydrothermal vents that correspond to particularly unstable environments.
      RESULTS: Using PCR approaches, we have identified 15 new DIRS1-like families in
      15 diverse decapod species (shrimps, lobsters, crabs and galatheid crabs).
      Hydrothermal organisms show a particularly great diversity of DIRS1-like elements
      with 5 families characterized among Alvinocarididae shrimps and 3 in the
      galatheid crab Munidopsis recta. Phylogenic analyses show that these elements are
      divergent toward the DIRS1-like families previously described in other
      crustaceans and arthropods and form a new clade called AlDIRS1. At larger scale,
      the distribution of DIRS1-like retrotransposons appears more or less patchy
      depending on the taxa considered. Indeed, a scattered distribution can be
      observed in the infraorder Brachyura whereas all the species tested in
      infraorders Caridea and Astacidea harbor some DIRS1-like elements. CONCLUSION:
      Our results lead to nearly double both the number of DIRS1-like elements
      described to date, and the number of species known to harbor these ones. In this
      study, we provide the first degenerate primers designed to look specifically for
      DIRS1-like retrotransposons. They allowed for revealing for the first time a
      widespread distribution of these elements among a large phylum, here the order
      Decapoda. They also suggest some peculiar features of these retrotransposons in
      hydrothermal organisms where a great diversity of elements is already observed.
      Finally, this paper constitutes the first essential step which allows for
      considering further studies based on the dynamics of the DIRS1-like
      retrotransposons among several genomes.

PMID- 19400951
TI  - Analysis of the role of COP9 Signalosome (CSN) subunits in K562; the first link
      between CSN and autophagy.
AB  - BACKGROUND: The COP9/signalosome (CSN) is a highly conserved eight subunit
      complex that, by deneddylating cullins in cullin-based E3 ubiquitin ligases,
      regulates protein degradation. Although studied in model human cell lines such as
      HeLa, very little is known about the role of the CSN in haemopoietic cells.
      RESULTS: Greater than 95% knockdown of the non-catalytic subunit CSN2 and the
      deneddylating subunit CSN5 of the CSN was achieved in the human myeloid
      progenitor cell line K562. CSN2 knockdown led to a reduction of both CSN5 protein
      and mRNA whilst CSN5 knockdown had little effect on CSN2. Both knockdowns
      inhibited CSN deneddylase function as demonstrated by accumulation of neddylated
      Cul1. Furthermore, both knockdowns resulted in the sequential loss of Skp2, Cdc4
      and beta-TrCP F-box proteins. These proteins were rescued by the proteasome
      inhibitor MG132, indicating the autocatalytic degradation of F-box proteins upon
      loss of CSN2 or CSN5. Interestingly, altered F-box protein gene expression was
      also observed in CSN2 and CSN5 knockdowns, suggesting a potential role of the CSN
      in regulating F-box protein transcription.Loss of either CSN subunit dramatically
      reduced cell growth but resulted in distinct patterns of cell death. CSN5
      knockdown caused mitotic defects, G2/M arrest and apoptotic cell death. CSN2
      knockdown resulted in non-apoptotic cell death associated with accumulation of
      both the autophagy marker LC3-II and autophagic vacuoles. Treatment of vector
      control K562 cells with the autophagy inhibitors 3-methyladenine and bafilomycin
      A1 recapitulated the growth kinetics, vacuolar morphology and LC3-II accumulation
      of CSN2 knockdown cells indicating that the cellular phenotype of CSN2 cells
      arises from autophagy inhibition. Finally, loss of CSN2 was associated with the
      formation of a CSN5 containing subcomplex. CONCLUSION: We conclude that CSN2 is
      required for CSN integrity and the stability of individual CSN subunits, and
      postulate that CSN2 loss results in a phenotype distinct from that of cells
      lacking CSN5 possibly as a consequence of altered CSN5 activity within a
      resultant CSN subcomplex. Our data present the first evidence for the sequential
      loss of F-box proteins upon CSN manipulation and are the first to identify a
      potential link between CSN function and autophagy.

PMID- 19400950
TI  - Activation of p53-regulated pro-apoptotic signaling pathways in PrP-mediated
      myopathy.
AB  - BACKGROUND: We have reported that doxycycline-induced over-expression of wild
      type prion protein (PrP) in skeletal muscles of Tg(HQK) mice is sufficient to
      cause a primary myopathy with no signs of peripheral neuropathy. The preferential
      accumulation of the truncated PrP C1 fragment was closely correlated with these
      myopathic changes. In this study we use gene expression profiling to explore the
      temporal program of molecular changes underlying the PrP-mediated myopathy.
      RESULTS: We used DNA microarrays, and confirmatory real-time PCR and Western blot
      analysis to demonstrate deregulation of a large number of genes in the course of
      the progressive myopathy in the skeletal muscles of doxycycline-treated Tg(HQK)
      mice. These include the down-regulation of genes coding for the myofibrillar
      proteins and transcription factor MEF2c, and up-regulation of genes for lysosomal
      proteins that is concomitant with increased lysosomal activity in the skeletal
      muscles. Significantly, there was prominent up-regulation of p53 and p53
      regulated genes involved in cell cycle arrest and promotion of apoptosis that
      paralleled the initiation and progression of the muscle pathology. CONCLUSION:
      The data provides the first in vivo evidence that directly links p53 to a wild
      type PrP-mediated disease. It is evident that several mechanistic features
      contribute to the myopathy observed in PrP over-expressing mice and that p53
      related apoptotic pathways appear to play a major role.

PMID- 19400952
TI  - NR2B receptor blockade inhibits pain-related sensitization of amygdala neurons.
AB  - Pain-related sensitization and synaptic plasticity in the central nucleus of the
      amygdala (CeA) depend on the endogenous activation of NMDA receptors and
      phosphorylation of the NR1 subunit through a PKA-dependent mechanism. Functional
      NMDA receptors are heteromeric assemblies of NR1 with NR2A-D or NR3A, B subunits.
      NMDA receptors composed of NR1 and NR2B subunits have been implicated in
      neuroplasticity and are present in the CeA. Here we used a selective NR2B
      antagonist (Ro-256981) to determine the contribution of NR2B-containing NMDA
      receptors to pain-related sensitization of CeA neurons. Extracellular single-unit
      recordings were made from CeA neurons in anesthetized adult male rats before and
      during the development of an acute arthritis. Arthritis was induced in one knee
      joint by intraarticular injections of kaolin and carrageenan. Brief (15 s)
      mechanical stimuli of innocuous (100-500 g/30 mm2) and noxious (1000-2000 g/30
      mm2) intensity were applied to the knee and other parts of the body. In agreement
      with our previous studies, all CeA neurons developed increased background and
      evoked activity after arthritis induction. Ro-256981 (1, 10 and 100 muM; 15 min
      each) was administered into the CeA by microdialysis 5-6 h postinduction of
      arthritis. Ro-256981 concentration-dependently decreased evoked responses, but
      not background activity. This pattern of effect is different from that of an NMDA
      receptor antagonist (AP5) in our previous studies. AP5 (100 microM - 5 mM)
      inhibited background activity and evoked responses. The differential effects of
      AP5 and Ro-256981 may suggest that NMDA receptors containing the NR2B subunit are
      important but not sole contributors to pain-related changes of CeA neurons.

PMID- 19400953
TI  - A retrospective analysis of the change in anti-malarial treatment policy: Peru.
AB  - BACKGROUND: National malaria control programmes must deal with the complex
      process of changing national malaria treatment guidelines, often without guidance
      on the process of change. Selecting a replacement drug is only one issue in this
      process. There is a paucity of literature describing successful malaria treatment
      policy changes to help guide control programs through this process. OBJECTIVES:
      To understand the wider context in which national malaria treatment guidelines
      were formulated in a specific country (Peru). METHODS: Using qualitative methods
      (individual and focus group interviews, stakeholder analysis and a review of
      documents), a retrospective analysis of the process of change in Peru's anti
      malarial treatment policy from the early 1990's to 2003 was completed. RESULTS:
      The decision to change Peru's policies resulted from increasing levels of anti
      malarial drug resistance, as well as complaints from providers that the drugs
      were no longer working. The context of the change occurred in a time in which
      Peru was changing national governments, which created extreme challenges in
      moving the change process forward. Peru utilized a number of key strategies
      successfully to ensure that policy change would occur. This included a) having
      the process directed by a group who shared a common interest in malaria and who
      had long-established social and professional networks among themselves, b)
      engaging in collaborative teamwork among nationals and between nationals and
      international collaborators, c) respect for and inclusion of district-level staff
      in all phases of the process, d) reliance on high levels of technical and
      scientific knowledge, e) use of standardized protocols to collect data, and f)
      transparency. CONCLUSION: Although not perfectly or fully implemented by 2003,
      the change in malaria treatment policy in Peru occurred very quickly, as compared
      to other countries. They identified a problem, collected the data necessary to
      justify the change, utilized political will to their favor, approved the policy,
      and moved to improve malaria control in their country. As such, they offer an
      excellent example for other countries as they contemplate or embark on policy
      changes.

PMID- 19400954
TI  - Vaccinia virus p37 interacts with host proteins associated with LE-derived
      transport vesicle biogenesis.
AB  - BACKGROUND: Proteins associated with the late endosome (LE) appear to play a
      central role in the envelopment of a number of taxonomically diverse viruses. How
      viral proteins interact with LE-associated proteins to facilitate envelopment is
      not well understood. LE-derived transport vesicles form through the interaction
      of Rab9 GTPase with cargo proteins, and TIP47, a Rab9-specific effector protein.
      Vaccinia virus (VV) induces a wrapping complex derived from intracellular host
      membranes to envelope intracellular mature virus particles producing egress
      competent forms of virus. RESULTS: We show that VV p37 protein associates with
      TIP47-, Rab9-, and CI-MPR-containing membranes. Mutation of a di-aromatic motif
      in p37 blocks association with TIP47 and inhibits plaque formation. ST-246, a
      specific inhibitor of p37 function, inhibits these interactions and also blocks
      wrapped virus particle formation. Vaccinia virus expressing p37 variants with
      reduced ST-246 susceptibility associates with Rab9 and co-localizes with CI-MPR
      in the presence and absence of compound. CONCLUSION: These results suggest that
      p37 localizes to the LE and interacts with proteins associated with LE-derived
      transport vesicle biogenesis to facilitate assembly of extracellular forms of
      virus.

PMID- 19400955
TI  - Offspring of parents with Balkan Endemic Nephropathy have higher C-reactive
      protein levels suggestive of inflammatory processes: a longitudinal study.
AB  - BACKGROUND: Despite the characteristic extensive tubulointerstitial fibrosis,
      Balkan Endemic Nephropathy (BEN) is usually considered a non-inflammatory
      disease. METHODS: We examined a marker of inflammation, C-reactive protein (CRP),
      in the offspring of patients with BEN, a population at risk for BEN, prior to
      development of established disease to determine if an inflammatory process could
      be identified in the early stages of the disease. In 2003/04, 102 adult offspring
      whose parents had BEN and a control group of 99 adult offspring of non-BEN
      patients were enrolled in this prospective study. This cohort was re-examined
      yearly for four consecutive years. Levels of serum CRP were measured in years 3
      and 4 and compared between groups. The data were analyzed with mixed models.
      RESULTS: Compared to controls, offspring of BEN parents had statistically higher
      CRP levels in two consecutive years, suggestive of early inflammatory reactivity.
      Whenever the mother was affected by BEN (both parents, or mother only), serum CRP
      was significantly increased, but not if only the father had BEN. CRP was
      inversely related to kidney cortex width but not to markers or renal function.
      CONCLUSION: Early stages of BEN may involve inflammatory processes. The
      observation of a maternal involvement supports the concept of fetal programming,
      which has been implicated in the pathogenesis of other chronic kidney diseases.

PMID- 19400956
TI  - The Daughterless N-terminus directly mediates synergistic interactions with Notch
      transcription complexes via the SPS+A DNA transcription code.
AB  - BACKGROUND: Cell-specific expression of a subset of Enhancer of split (E(spl)-C)
      genes in proneural clusters is mediated by synergistic interactions between bHLH
      A (basic Helix-Loop-Helix Activator) and Notch-signalling transcription complex
      (NTC) proteins. For a some of these E(spl)-C genes, such as m8, these synergistic
      interactions are programmed by an "SPS+A" transcription code in the cis
      regulatory regions. However, the molecular mechanisms underlying this synergistic
      interaction between NTCs and proneural bHLH A proteins are not fully understood.
      FINDINGS: Using cell transcription assays, we show that the N-terminal region of
      the Daughterless (Da) bHLH A protein is critical for synergistic interactions
      with NTCs that activate the E(spl)-C m8 promoter. These assays also show that
      this interaction is dependent on the specific inverted repeat architecture of
      Suppressor of Hairless (Su(H)) binding sites in the SPS+A transcription code.
      Using protein-protein interaction assays, we show that two distinct regions
      within the Da N-terminus make a direct physical interaction with the NTC protein
      Su(H). Deletion of these interaction domains in Da creates a dominant negative
      protein that eliminates NTC-bHLH A transcriptional synergy on the m8 promoter. In
      addition, over-expression of this dominant negative Da protein disrupts Notch
      mediated lateral inhibition during mechanosensory bristle neurogenesis in vivo.
      CONCLUSION: These findings indicate that direct physical interactions between Da
      N and Su(H) are critical for the transcriptional synergy between NTC and bHLH A
      proteins on the m8 promoter. Our results also indicate that the orientation of
      the Su(H) binding sites in the SPS+A transcription code are critical for
      programming the interaction between Da-N and Su(H) proteins. Together, these
      findings provide insight into the molecular mechanisms by which the NTC
      synergistically interacts with bHLH A proteins to mediate Notch target gene
      expression in proneural clusters.

PMID- 19400957
TI  - Tamoxifen-elicited uterotrophy: cross-species and cross-ligand analysis of the
      gene expression program.
AB  - BACKGROUND: Tamoxifen (TAM) is a well characterized breast cancer drug and
      selective estrogen receptor modulator (SERM) which also has been associated with
      a small increase in risk for uterine cancers. TAM's partial agonist activation of
      estrogen receptor has been characterized for specific gene promoters but not at
      the genomic level in vivo.Furthermore, reducing uncertainties associated with
      cross-species extrapolations of pharmaco- and toxicogenomic data remains a
      formidable challenge. RESULTS: A comparative ligand and species analysis approach
      was conducted to systematically assess the physiological, morphological and
      uterine gene expression alterations elicited across time by TAM and
      ethynylestradiol (EE) in immature ovariectomized Sprague-Dawley rats and C57BL/6
      mice. Differential gene expression was evaluated using custom cDNA microarrays,
      and the data was compared to identify conserved and divergent responses. 902
      genes were differentially regulated in all four studies, 398 of which exhibit
      identical temporal expression patterns. CONCLUSION: Comparative analysis of EE
      and TAM differentially expressed gene lists suggest TAM regulates no unique
      uterine genes that are conserved in the rat and mouse. This demonstrates that the
      partial agonist activities of TAM extend to molecular targets in regulating only
      a subset of EE-responsive genes. Ligand-conserved, species-divergent expression
      of carbonic anhydrase 2 was observed in the microarray data and confirmed by real
      time PCR. The identification of comparable temporal phenotypic responses linked
      to related gene expression profiles demonstrates that systematic comparative
      genomic assessments can elucidate important conserved and divergent mechanisms in
      rodent estrogen signalling during uterine proliferation.

PMID- 19400958
TI  - Age-standardized incidence and mortality rates of oral and pharyngeal cancer in
      Puerto Rico and among Non-Hispanics Whites, Non-Hispanic Blacks, and Hispanics in
      the USA.
AB  - BACKGROUND: In the American region, Puerto Rico (PR) has the highest incidence of
      oral and pharyngeal cancer (OPC), but racial/ethnic differences have never been
      assessed and compared with other groups in the United States of America (USA). We
      compared the age-adjusted incidence and mortality rates of OPC between PR and
      among USA Hispanics (USH), Non-Hispanic Whites (NHW), and Non-Hispanic Blacks
      (NHB) to assess the burden of this cancer in PR. METHODS: Analysis of the age
      standardized rates (per 100,000) was performed using the direct method with the
      world standard population (ASR(World)) from 1998-2002. Annual percent change
      (APC) and Relative Risks (RR) were calculated using the Poisson regression model.
      RESULTS: The incidence ASR(World) for men in PR was constant (APC approximately
      0.0%), in contrast, a decrease was observed among NHW, NHB, and USH men, although
      only USH showed statistical significance (APC = -4.9%, p < 0.05). In women, the
      highest increase in incidence (APC = 5.3%) and the lowest decrease in mortality
      (APC = -1.4%) was observed in PR. The ratio of the ASR(World) showed that in all
      racial/ethnic groups, men had approximately 2-4 fold increased incidence and
      mortality risk of OPC than women (p < 0.05). Men in PR had a higher mortality
      risk (p < 0.05) of OPC as compared to USH, NHW, and NHB; but among women, PR
      showed a significant excess of mortality only as compared to USH (est. SRR =
      1.82, 95% CI = 1.41, 2.33). CONCLUSION: The overall higher incidence of OPC in
      men in PR as compared to USH, NHB, and NHW could be explained by the effect of
      gene-environment interactions. Meanwhile, the higher mortality from OPC in PR
      suggests limitations in the health-care access within this population. Further
      research is warranted to elucidate these findings.

PMID- 19400959
TI  - Using molecular similarity to highlight the challenges of routine immunoassay
      based drug of abuse/toxicology screening in emergency medicine.
AB  - BACKGROUND: Laboratory tests for routine drug of abuse and toxicology (DOA/Tox)
      screening, often used in emergency medicine, generally utilize antibody-based
      tests (immunoassays) to detect classes of drugs such as amphetamines,
      barbiturates, benzodiazepines, opiates, and tricyclic antidepressants, or
      individual drugs such as cocaine, methadone, and phencyclidine. A key factor in
      assay sensitivity and specificity is the drugs or drug metabolites that were used
      as antigenic targets to generate the assay antibodies. All DOA/Tox screening
      immunoassays can be limited by false positives caused by cross-reactivity from
      structurally related compounds. For immunoassays targeted at a particular class
      of drugs, there can also be false negatives if there is failure to detect some
      drugs or their metabolites within that class. METHODS: Molecular similarity
      analysis, a computational method commonly used in drug discovery, was used to
      calculate structural similarity of a wide range of clinically relevant compounds
      (prescription and over-the-counter medications, illicit drugs, and clinically
      significant metabolites) to the target ('antigenic') molecules of DOA/Tox
      screening tests. These results were compared with cross-reactivity data in the
      package inserts of immunoassays marketed for clinical testing. The causes for
      false positives for phencyclidine and tricyclic antidepressant screening
      immunoassays were investigated at the authors' medical center using gas
      chromatography/mass spectrometry as a confirmatory method. RESULTS: The results
      illustrate three major challenges for routine DOA/Tox screening immunoassays used
      in emergency medicine. First, for some classes of drugs, the structural diversity
      of common drugs within each class has been increasing, thereby making it
      difficult for a single assay to detect all compounds without compromising
      specificity. Second, for some screening assays, common 'out-of-class' drugs may
      be structurally similar to the target compound so that they account for a high
      frequency of false positives. Illustrating this point, at the authors' medical
      center, the majority of positive screening results for phencyclidine and
      tricyclic antidepressants assays were explained by out-of-class drugs. Third,
      different manufacturers have adopted varying approaches to marketed immunoassays,
      leading to substantial inter-assay variability. CONCLUSION: The expanding
      structural diversity of drugs presents a difficult challenge for routine DOA/Tox
      screening that limit the clinical utility of these tests in the emergency
      medicine setting.

PMID- 19400961
TI  - Protocol for the Proactive Or Reactive Telephone Smoking CeSsation Support
      (PORTSSS) trial.
AB  - BACKGROUND: Telephone quit lines are accessible to many smokers and are used to
      engage motivated smokers to make quit attempts. Smoking cessation counselling
      provided via telephone can either be reactive (i.e. primarily involving the
      provision of evidence-based information), or proactive (i.e. primarily involving
      repeated, sequenced calls from and interaction with trained cessation
      counsellors). Some studies have found proactive telephone counselling more
      effective and this trial will investigate whether or not proactive telephone
      support for smoking cessation, delivered through the National Health Service
      (NHS) Smoking Helpline is more effective or cost-effective than reactive support.
      It will also investigate whether or not providing nicotine replacement therapy
      (NRT), in addition to telephone counselling, has an adjunctive impact on smoking
      cessation rates and whether or not this is cost effective. METHODS: This will be
      a parallel group, factorial design RCT, conducted through the English national
      NHS Smoking Helpline which is run from headquarters in Glasgow. Participants will
      be smokers who call the helpline from any location in England and who wish to
      stop smoking. If 644 participants are recruited to four equally-sized trial
      groups (total sample size = 2576), the trial will have 90% power for detecting a
      treatment effect (Odds Ratio) of 1.5 for each of the two interventions: i)
      proactive versus reactive support and ii) the offer of NRT versus no offer. The
      primary outcome measure for the study is self-reported, prolonged abstinence from
      smoking for at least six months following an agreed quit date. A concurrent
      health economic evaluation will investigate the cost effectiveness of the two
      interventions when delivered via a telephone helpline. DISCUSSION: The PORTSSS
      trial will provide high quality evidence to determine the most appropriate kind
      of counselling which should be provided via the NHS Smoking Helpline and also
      whether or not an additional offer of cost-free NRT is effective and cost
      effective for smoking cessation.

PMID- 19400960
TI  - Functional interleukin-17 receptor A is expressed in central nervous system glia
      and upregulated in experimental autoimmune encephalomyelitis.
AB  - BACKGROUND: Interleukin-17A (IL-17A) is the founding member of a novel family of
      inflammatory cytokines that plays a critical role in the pathogenesis of many
      autoimmune diseases, including multiple sclerosis (MS) and its animal model,
      experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its
      receptor, IL-17RA, which is expressed in many peripheral tissues; however,
      expression of IL-17RA in the central nervous system (CNS) and its role in CNS
      inflammation are not well understood. METHODS: EAE was induced in C57Bl/6 mice by
      immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the
      CNS was compared between control and EAE mice using RT-PCR, in situ
      hybridization, and immunohistochemistry. Cell-type specific expression was
      examined in isolated astrocytic and microglial cell cultures. Cytokine and
      chemokine production was measured in IL-17A treated cultures to evaluate the
      functional status of IL-17RA. RESULTS: Here we report increased IL-17RA
      expression in the CNS of mice with EAE, and constitutive expression of functional
      IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL
      17RA in vitro, and IL-17A treatment induces biological responses in these cells,
      including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine
      secretion. Exogenous IL-17A does not significantly alter the expression of IL
      17RA in glial cells, suggesting that upregulation of chemokines by glial cells is
      due to IL-17A signaling through constitutively expressed IL-17RA. CONCLUSION: IL
      17RA expression is significantly increased in the CNS of mice with EAE compared
      to healthy mice, suggesting that IL-17RA signaling in glial cells can play an
      important role in autoimmune inflammation of the CNS and may be a potential
      pathway to target for therapeutic interventions.

PMID- 19400962
TI  - Reusable, polyethylene glycol-structured microfluidic channel for particle
      immunoassays.
AB  - A microfluidic channel made entirely out of polyethylene glycol (PEG), not PEG
      coating to silicon or polydimethylsiloxane (PDMS) surface, was fabricated and
      tested for its reusability in particle immunoassays and passive protein fouling,
      at relatively high target concentrations (1 mg ml(-1)). The PEG devices were
      reusable up to ten times while the oxygen-plasma-treated polydimethyl siloxane
      (PDMS) device could be reused up to four times and plain PDMS were not reusable.
      Liquid was delivered spontaneously via capillary action and complicated bonding
      procedure was not necessary. The contact angle analysis revealed that the water
      contact angle on microchannel surface should be lower than approximately 60
      degrees , which are comparable to those on dried protein films, to be reusable
      for particle immunoassays and passive protein fouling.

PMID- 19400963
TI  - Dealing with uncertainties in environmental burden of disease assessment.
AB  - Disability Adjusted Life Years (DALYs) combine the number of people affected by
      disease or mortality in a population and the duration and severity of their
      condition into one number. The environmental burden of disease is the number of
      DALYs that can be attributed to environmental factors. Environmental burden of
      disease estimates enable policy makers to evaluate, compare and prioritize
      dissimilar environmental health problems or interventions. These estimates often
      have various uncertainties and assumptions which are not always made explicit.
      Besides statistical uncertainty in input data and parameters - which is commonly
      addressed - a variety of other types of uncertainties may substantially influence
      the results of the assessment. We have reviewed how different types of
      uncertainties affect environmental burden of disease assessments, and we give
      suggestions as to how researchers could address these uncertainties. We propose
      the use of an uncertainty typology to identify and characterize uncertainties.
      Finally, we argue that uncertainties need to be identified, assessed, reported
      and interpreted in order for assessment results to adequately support decision
      making.

PMID- 19400964
TI  - Interrater reliability of the mind map assessment rubric in a cohort of medical
      students.
AB  - BACKGROUND: Learning strategies are thinking tools that students can use to
      actively acquire information. Examples of learning strategies include mnemonics,
      charts, and maps. One strategy that may help students master the tsunami of
      information presented in medical school is the mind map learning strategy.
      Currently, there is no valid and reliable rubric to grade mind maps and this may
      contribute to their underutilization in medicine. Because concept maps and mind
      maps engage learners similarly at a metacognitive level, a valid and reliable
      concept map assessment scoring system was adapted to form the mind map assessment
      rubric (MMAR). The MMAR can assess mind map depth based upon concept-links, cross
      links, hierarchies, examples, pictures, and colors. The purpose of this study was
      to examine interrater reliability of the MMAR. METHODS: This exploratory study
      was conducted at a US medical school as part of a larger investigation on
      learning strategies. Sixty-six (N = 66) first-year medical students were given a
      394-word text passage followed by a 30-minute presentation on mind mapping. After
      the presentation, subjects were again given the text passage and instructed to
      create mind maps based upon the passage. The mind maps were collected and
      independently scored using the MMAR by 3 examiners. Interrater reliability was
      measured using the intraclass correlation coefficient (ICC) statistic. Statistics
      were calculated using SPSS version 12.0 (Chicago, IL). RESULTS: Analysis of the
      mind maps revealed the following: concept-links ICC = .05 (95% CI, -.42 to .38),
      cross-links ICC = .58 (95% CI, .37 to .73), hierarchies ICC = .23 (95% CI, -.15
      to .50), examples ICC = .53 (95% CI, .29 to .69), pictures ICC = .86 (95% CI, .79
      to .91), colors ICC = .73 (95% CI, .59 to .82), and total score ICC = .86 (95%
      CI, .79 to .91). CONCLUSION: The high ICC value for total mind map score
      indicates strong MMAR interrater reliability. Pictures and colors demonstrated
      moderate to strong interrater reliability. We conclude that the MMAR may be a
      valid and reliable tool to assess mind maps in medicine. However, further
      research on the validity and reliability of the MMAR is necessary.

PMID- 19400965
TI  - Regulation of chk1.
AB  - Chk1 is a serine/threonine protein kinase that is the effector of the G2 DNA
      damage checkpoint. Chk1 homologs have a highly conserved N-terminal kinase
      domain, and a less conserved C-terminal regulatory domain of ~200 residues. In
      response to a variety of genomic lesions, a number of proteins collaborate to
      activate Chk1, which in turn ensures that the mitotic cyclin-dependent kinase
      Cdc2 remains in an inactive state until DNA repair is completed. Chk1 activation
      requires the phosphorylation of residues in the C-terminal domain, and this is
      catalyzed by the ATR protein kinase. How phosphorylation of the C-terminal
      regulatory domain activates the N-terminal kinase domain has not been elucidated,
      though some studies have suggested that this phosphorylation relieves an
      inhibitory intramolecular interaction between the N- and C-termini. However,
      recent studies in the fission yeast Schizosaccharomyces pombe have revealed that
      there is more to Chk1 regulation than this auto-inhibition model, and we review
      these findings and their implication to the biology of this genome integrity
      determinant.

PMID- 19400966
TI  - Measuring the impact and distress of osteoarthritis from the patients'
      perspective.
AB  - BACKGROUND: To assess the internal construct validity of the Perceived Impact of
      Problem Profile (PIPP), a patient based outcome measure based on the
      International Classification of Functioning, Disability and Health (ICF), which
      assesses impact and distress, in an osteoarthritis (OA) cohort. METHODS: A
      questionnaire comprising the 23-item PIPP, which assesses five domains (mobility,
      participation, self care, psychological well being and relationships), the
      Western Ontario McMasters University Osteoarthritis Index (WOMAC), the General
      Well-Being Index (GWBI), and the Hospital Anxiety and Depression Scale (HADS) was
      posted to people with clinician diagnosed OA. Assessment of the internal
      construct validity of the PIPP was undertaken using Rasch analysis performed with
      RUMM2020 software and concurrent validity through comparator measures. RESULTS:
      Two hundred and fifty-nine participants with OA responded. Analysis of the five
      individual domains of the PIPP indicated that there was good fit to the Rasch
      model, with high person separation reliability. One item required removal from
      the Mobility subscale and the Participation subscale. There were strong
      correlations between the PIPP Mobility scores and the WOMAC disability and pain
      subscales (rho = .73 and rho = .68), and between the PIPP Psychological well
      being and HADS Depression (rho = .71) and GWBI (rho = -.69). High inter
      correlations between the impact and distress subscales for each domain (range rho
      = .85 to .96), suggested redundancy of the latter. CONCLUSION: This study
      demonstrates that the PIPP has good psychometric properties in an OA population.
      The PIPP, using just the impact subscales, provides a brief, reliable and valid
      means of assessing the impact of OA from the individual's perspective and
      operationalizing the bio-psychosocial model by the application of a single multi
      domain questionnaire.

PMID- 19400967
TI  - Subsampling effects in neuronal avalanche distributions recorded in vivo.
AB  - BACKGROUND: Many systems in nature are characterized by complex behaviour where
      large cascades of events, or avalanches, unpredictably alternate with periods of
      little activity. Snow avalanches are an example. Often the size distribution f(s)
      of a system's avalanches follows a power law, and the branching parameter sigma,
      the average number of events triggered by a single preceding event, is unity. A
      power law for f(s), and sigma = 1, are hallmark features of self-organized
      critical (SOC) systems, and both have been found for neuronal activity in vitro.
      Therefore, and since SOC systems and neuronal activity both show large
      variability, long-term stability and memory capabilities, SOC has been proposed
      to govern neuronal dynamics in vivo. Testing this hypothesis is difficult because
      neuronal activity is spatially or temporally subsampled, while theories of SOC
      systems assume full sampling. To close this gap, we investigated how subsampling
      affects f(s) and sigma by imposing subsampling on three different SOC models. We
      then compared f(s) and sigma of the subsampled models with those of
      multielectrode local field potential (LFP) activity recorded in three macaque
      monkeys performing a short term memory task. RESULTS: Neither the LFP nor the
      subsampled SOC models showed a power law for f(s). Both, f(s) and sigma, depended
      sensitively on the subsampling geometry and the dynamics of the model. Only one
      of the SOC models, the Abelian Sandpile Model, exhibited f(s) and sigma similar
      to those calculated from LFP activity. CONCLUSION: Since subsampling can prevent
      the observation of the characteristic power law and sigma in SOC systems,
      misclassifications of critical systems as sub- or supercritical are possible.
      Nevertheless, the system specific scaling of f(s) and sigma under subsampling
      conditions may prove useful to select physiologically motivated models of brain
      function. Models that better reproduce f(s) and sigma calculated from the
      physiological recordings may be selected over alternatives.

PMID- 19400968
TI  - Radiographic features of Mycoplasma pneumoniae pneumonia: differential diagnosis
      and performance timing.
AB  - BACKGROUND: The Japanese Respiratory Society guidelines propose a differential
      diagnosis for atypical pneumonia and bacterial pneumonia using a scoring system
      for the selection of appropriate antibiotic. In order to improve this scoring
      system, the guidelines are seeking new specific parameter. The purpose of this
      study was to clarify the pattern of abnormalities with Mycoplasma pneumoniae
      pneumonia on chest computed tomography (CT) and whether the radiographic findings
      could distinguish M. pneumoniae pneumonia from Streptococcus pneumoniae
      pneumonia. METHODS: A retrospective review was performed of the CT findings of 64
      cases and 68 cases where M. pneumoniae and S. pneumoniae, respectively, were the
      only pathogen identified by the panel of diagnostic tests used. RESULTS: Of the
      64 patients with M. pneumoniae pneumonia, bronchial wall thickening was observed
      most frequently (81%), followed by centrilobular nodules (78%), ground-glass
      attenuation (78%), and consolidation (61%). Bronchial wall thickening and
      centrilobular nodules were observed more often in M. pneumoniae patients than in
      S. pneumoniae patients (p < 0.0001). The presence of bilateral bronchial wall
      thickening or centrilobular nodules was only seen in patients with M. pneumoniae
      pneumonia. Using the scoring system of the Japanese Respiratory Society
      guidelines and chest CT findings, 97% of M. pneumoniae patients were suspected to
      be M. pneumoniae pneumonia without serology. When comparing the CT findings
      between early stage and progressed stage in the same patients with severe
      pneumonia, the radiographic features of early stage M. pneumoniae pneumonia were
      not observed clearly in the progressed stage. CONCLUSION: The present results
      indicate that the diagnosis of M. pneumoniae pneumonia would appear to be
      reliable when found with a combination of bronchial wall thickening and
      centrilobular nodules in the CT findings. However, these CT findings are not
      observed in progressed severe M. pneumoniae pneumonia patients.

PMID- 19400969
TI  - Computing travel time when the exact address is unknown: a comparison of point
      and polygon ZIP code approximation methods.
AB  - BACKGROUND: Travel time is an important metric of geographic access to health
      care. We compared strategies of estimating travel times when only subject ZIP
      code data were available. RESULTS: Using simulated data from New Hampshire and
      Arizona, we estimated travel times to nearest cancer centers by using: 1)
      geometric centroid of ZIP code polygons as origins, 2) population centroids as
      origin, 3) service area rings around each cancer center, assigning subjects to
      rings by assuming they are evenly distributed within their ZIP code, 4) service
      area rings around each center, assuming the subjects follow the population
      distribution within the ZIP code. We used travel times based on street addresses
      as true values to validate estimates. Population-based methods have smaller
      errors than geometry-based methods. Within categories (geometry or population),
      centroid and service area methods have similar errors. Errors are smaller in
      urban areas than in rural areas. CONCLUSION: Population-based methods are
      superior to the geometry-based methods, with the population centroid method
      appearing to be the best choice for estimating travel time. Estimates in rural
      areas are less reliable.

PMID- 19400970
TI  - Simulation suggests that rapid activation of social distancing can arrest
      epidemic development due to a novel strain of influenza.
AB  - BACKGROUND: Social distancing interventions such as school closure and
      prohibition of public gatherings are present in pandemic influenza preparedness
      plans. Predicting the effectiveness of intervention strategies in a pandemic is
      difficult. In the absence of other evidence, computer simulation can be used to
      help policy makers plan for a potential future influenza pandemic. We conducted
      simulations of a small community to determine the magnitude and timing of
      activation that would be necessary for social distancing interventions to arrest
      a future pandemic. METHODS: We used a detailed, individual-based model of a real
      community with a population of approximately 30,000. We simulated the effect of
      four social distancing interventions: school closure, increased isolation of
      symptomatic individuals in their household, workplace nonattendance, and
      reduction of contact in the wider community. We simulated each of the
      intervention measures in isolation and in several combinations; and examined the
      effect of delays in the activation of interventions on the final and daily attack
      rates. RESULTS: For an epidemic with an R0 value of 1.5, a combination of all
      four social distancing measures could reduce the final attack rate from 33% to
      below 10% if introduced within 6 weeks from the introduction of the first case.
      In contrast, for an R0 of 2.5 these measures must be introduced within 2 weeks of
      the first case to achieve a similar reduction; delays of 2, 3 and 4 weeks
      resulted in final attack rates of 7%, 21% and 45% respectively. For an R0 of 3.5
      the combination of all four measures could reduce the final attack rate from 73%
      to 16%, but only if introduced without delay; delays of 1, 2 or 3 weeks resulted
      in final attack rates of 19%, 35% or 63% respectively. For the higher R0 values
      no single measure has a significant impact on attack rates. CONCLUSION: Our
      results suggest a critical role of social distancing in the potential control of
      a future pandemic and indicate that such interventions are capable of arresting
      influenza epidemic development, but only if they are used in combination,
      activated without delay and maintained for a relatively long period.

PMID- 19400971
TI  - Sir David Cuthbertson Medal Lecture. Bariatric surgery as a model to study
      appetite control.
AB  - The obesity epidemic and its associated morbidity and mortality have led to major
      research efforts to identify mechanisms that regulate appetite. Gut hormones have
      recently been found to be an important element in appetite regulation as a result
      of the signals from the periphery to the brain. Candidate hormones include
      ghrelin, peptide YY, glucagon-like peptide-1 and gastric inhibitory polypeptide,
      all of which are currently being investigated as potential obesity treatments.
      Bariatric surgery is currently the most effective therapy for substantial and
      sustained weight loss. Understanding how levels of gut hormones are modulated by
      such procedures has greatly contributed to the comprehension of the underlying
      mechanisms of appetite and obesity. The present paper is a review of how appetite
      and levels of gastrointestinal hormones are altered after bariatric surgery.
      Basic principles of common bariatric procedures and potential mechanisms for
      appetite regulation by gut hormones are also addressed.

PMID- 19400972
TI  - Competent to care. A train-the-trainer method of teaching as a way of
      implementing the correct use of the 'Malnutrition Universal Screening Tool' in
      Norfolk: is it effective?
AB  - Malnutrition is frequently undetected in care homes. It is recommended that
      residents are screened on admission and at suitable intervals thereafter. It is
      aimed to implement the 'Malnutrition Universal Screening Tool' ('MUST') in all
      care homes in Norfolk in order to fulfil this recommendation. Following a pilot
      of successful (but time-consuming) 'MUST' training a train-the-trainer package
      was developed as a practical way of achieving this goal. Courses were held in
      2007, each comprising a study day and an assessment of each trainer delivering
      training. Trainers were provided with a dossier of training support materials.
      Data were collected at the study day and 3 months after the course to evaluate
      its effectiveness. Sixty-seven trainers were trained, all of whom rated the
      course as effective in preparing them to deliver training. At their assessments
      96% were able to explain 'MUST' accurately. Of the new trainers 44% returned
      follow-up questionnaires and copies of sample care plans. The majority of care
      plans showed 'MUST' scores had been calculated accurately and appropriate
      nutrition care plans had been set up and evaluated. The train-the-trainer model
      is an effective method of training large numbers of care-home staff to use
      'MUST'. One of the unexpected benefits observed was the ownership taken by the
      trainers, which was demonstrated by the enthusiasm and confidence with which they
      subsequently trained their colleagues.

PMID- 19400973
TI  - Impact of growth patterns and early diet on obesity and cardiovascular risk
      factors in young children from developing countries.
AB  - Non-communicable chronic diseases are now a worldwide epidemic. Diet and physical
      activity throughout life are among its main determinants. In countries undergoing
      the early stages of the nutrition transition weight gain from birth to 2 years of
      life is related to lean mass gain, while ponderal gain after age 2 years is
      related to adiposity and later diabetes and CVD risk. Evidence from developing
      countries undergoing the more advanced stages of the nutrition transition is
      limited. The early growth patterns of a cohort of Chilean children born in 2002
      with normal birth weight who at 4 years had a high prevalence of obesity and CVD
      risk factors have been assessed. Results indicate that BMI gain in early life,
      particularly from 6 months to 24 months, is positively associated with adiposity
      and CVD risk status at 4 years. These results together with existing evidence
      suggest that actions to prevent obesity and nutrition-related chronic diseases in
      developing countries should start early in life, possibly after 6 months of age.
      This approach should consider assessing the effect of mode of feeding and the
      amount and type of energy fed, as well as the resulting growth patterns. The
      challenge for researchers addressing the nutrition transition is to define the
      optimal nutrition in early life, considering not only the short- and long-term
      health consequences but also taking into account the stage of the nutritional
      transition for the given population of interest. The latter will probably require
      redefining optimal postnatal growth based on the context of maternal size and
      fetal growth.

PMID- 19400974
TI  - Teams, strategies and networks: developments in nutritional support; a personal
      perspective.
AB  - Chris Pennington was an archetypal team player, strategist and networker.
      Clinical nutritional support has progressed remarkably since the 1970s and it has
      been a privilege to work in this field over this period during which teamwork,
      strategy development and networking have been crucial. British experience has
      been characterised by groups of individuals of differing professions and
      specialties coming together to enable progress to be made. This approach was
      initially in the form of nutrition support teams orientated to patient-centred
      ward-based care, then as hospital strategic committees and the concept of the
      'patient journey'. Indeed, the formation of the British Association for
      Parenteral and Enteral Nutrition (now known as BAPEN) in 1992 required the
      statesmanlike burying of jealousies as societies came together into a
      multiprofessional association. With the understanding that disease-related
      malnutrition was highly prevalent it became apparent that it must be managed on a
      broad and organised clinical front. In the Organisation of Food and Nutritional
      Support in Hospitals a group of professionals developed for BAPEN concepts of
      hospital-wide organisation to tackle malnutrition that were based on previous
      reports, both national and international, and were made easily accessible from
      the BAPEN website, especially the 'Malnutrition Universal Screening Tool' and the
      National Institute for Health and Clinical Excellence nutrition guidelines. The
      coming together of six national clinical societies to develop evidence-based
      consensus guidelines for intravenous saline therapy (also on the BAPEN website)
      has shown that BAPEN can catalyse opinion well beyond its own nutritional
      constituency. In England Chris Pennington's Scottish lead is being followed by
      developing a patient-centred strategic framework for a managed home parenteral
      nutrition and intestinal failure national network. In research, education or
      clinical practice the engines of progress have been teams, strategies and
      networks.

PMID- 19400975
TI  - The 2-year prognosis of panic episodes in the general population.
AB  - BACKGROUND: Panic disorder (PD) is generally considered to be a chronic or
      intermittent disorder. This view may be biased because of a lack of general
      population studies investigating panic from the onset of an episode onwards. Data
      regarding the course of subthreshold panic disorder (sub-PD) and predictors of
      its course are lacking. METHOD: Using data from a large community-based survey,
      the Netherlands Mental Health and Incidence Study (NEMESIS), that retrospectively
      assessed the 2-year course of panic with a Life Chart Interview (LCI), this study
      investigated remission, chronicity and recurrence in subjects with new episodes
      of PD or sub-PD. Predictor variables of remission consisted of sociodemographics,
      psychobiological, environmental, psychiatric and panic-related factors. RESULTS:
      In PD, remission of panic attacks occurred in 64.5% of subjects, mean time to
      remission was 5.7 months, and the remission rate was 5.8/100 person-months. In
      43.3% of subjects panic was still present after 1 year. Recurrence of panic
      attacks occurred in 21.4% of those with PD who had achieved remission and for
      whom sufficient follow-up time was available. In general, the course of sub-PD
      was more favourable. Predictors of remission were female gender, the absence of
      ongoing difficulties, subthreshold panic and a low initial frequency of attacks.
      CONCLUSIONS: These results suggest that the course of panic is diverse in the
      general population, thereby underlining the need for accurate predictors. This
      requires further research including biological data and additional psychological
      data. In addition, given the large proportion with a relapse, relapse prevention
      should be part of any treatment programme.

PMID- 19400976
TI  - Cognitive functions and glycemic control in children and adolescents with type 1
      diabetes.
AB  - BACKGROUND: The relationship between metabolic control and cognitive function in
      adolescents with type 1 diabetes (DM type 1) is not clear. We compared the
      quality of glycemic control (GC) and cognitive measures in adolescents with DM
      type 1 to find out if the quality of diabetes management is related to cognitive
      impairment. METHOD: We assessed executive functions (EFs) and other
      neuropsychological and psychosocial variables in 70 adolescent patients with DM
      type 1 and 20 age-matched controls. Patients were divided into two groups
      according to their last hemoglobin A1c (HbA1c): acceptable (HbA1c 5.9-8.0%, mean
      6.9%, 36 patients, mean age 14 years) and non-optimal (HbA1c 8.2-11.6%, mean
      9.3%, 34 patients, mean age 15.6 years). RESULTS: We found impaired EFs, mainly
      problems of concept formation (p=0.038), cognitive flexibility (p=0.011) and
      anticipation (p=0.000), in the patients with DM type 1. Both groups did not
      differ in intelligence, most assessed EFs and adjustment to chronic illness
      (Youth Self-Report; YSR). Younger patients (<15 years) were cognitively less
      flexible. GC was worse in older patients and in patients with longer duration of
      the disease. We also found significant differences between patients with diabetes
      and controls concerning somatic complaints, internalizing problems (Child
      Behavior Checklist; CBCL) and social activity (CBCL and YSR). CONCLUSIONS: DM
      type 1 is associated with cognitive deficits in adolescents independent of the
      quality of metabolic control and the duration of the disease. These deficits are
      probably related to the disease, especially in patients with early-onset
      diabetes.

PMID- 19400977
TI  - A psychometric evaluation of the DSM-IV borderline personality disorder criteria:
      age and sex moderation of criterion functioning.
AB  - BACKGROUND: Despite its importance as a paradigmatic personality disorder, little
      is known about the measurement invariance of the DSM-IV borderline personality
      disorder (BPD) criteria; that is, whether the criteria assess the disorder
      equivalently across different groups. METHOD: BPD criteria were evaluated at
      interview in 2794 young adult Norwegian twins. Analyses, based on item-response
      modeling, were conducted to test for differential age and sex moderation of the
      individual BPD criteria characteristics given factor-level covariate effects.
      RESULTS: Confirmatory factor analytic results supported a unidimensional
      structure for the nine BPD criteria. Compared to males, females had a higher BPD
      factor mean, larger factor variance and there was a significant age by sex
      interaction on the factor mean. Strong differential sex and age by sex
      interaction effects were found for the 'impulsivity' criterion factor loading and
      threshold. Impulsivity related to the BPD factor poorly in young females but
      improved significantly in older females. Males reported more impulsivity compared
      to females and this difference increased with age. The 'affective instability'
      threshold was also moderated, with males reporting less than expected.
      CONCLUSIONS: The results suggest the DSM-IV BPD 'impulsivity' and 'affective
      instability' criteria function differentially with respect to age and sex, with
      impulsivity being especially problematic. If verified, these findings have
      important implications for the interpretation of prior research with these
      criteria. These non-invariant age and sex effects may be identifying criteria
      level expression features relevant to BPD nosology and etiology. Criterion
      functioning assessed using modern psychometric methods should be considered in
      the development of DSM-V.

PMID- 19400978
TI  - Preterm babies grown up: understanding a hidden  public health problem.
AB  - Even when they have grown up, the survivors of preterm birth are at increased
      risk of psychiatric illness. As the incidence of preterm birth is increasing,
      there is now a growing population of adults whose mental health needs have been
      neglected.

PMID- 19400980
TI  - Differential modulation of intracellular Ca2+ responses in B lymphoblasts by mood
      stabilizers.
AB  - Irregularities of intracellular calcium (Ca2+) homeostasis have been implicated
      in the pathophysiology of bipolar disorder (BD). Findings that chronic ex-vivo
      treatment with lithium modifies lysophosphatidic acid (LPA)-stimulated Ca2+
      responses in B lymphoblast cell lines (BLCLs) from BD-I patients and healthy
      controls, and differentially decreases levels of the type-3 canonical transient
      receptor potential Ca2+-permeable channel in BLCLs from BD-I patients, support
      the view that the amelioration of these abnormalities is important in the
      therapeutic action of lithium. To determine whether other clinically efficacious
      mood stabilizers share these effects, LPA (100 mum)- and thapsigargin (TG, 200
      nm)-stimulated Ca2+ responses were determined in BLCLs from BD-I patients and
      healthy controls treated acutely (24 h) and chronically (7 d) ex vivo with
      therapeutically relevant concentrations of lithium (0.75 mm), valproate (0.5 mm),
      lamotrigine (15 mum) or respective vehicles. Chronic treatment with valproate
      significantly attenuated LPA-stimulated Ca2+ responses ([downward arrow]8%:
      F's=9.1-9.4, d.f.=1, 9, p's<0.05) compared to vehicle in BLCLs from BD-I patients
      and healthy controls, similar to chronic lithium treatment ([downward arrow]8%:
      F=6.2, d.f.=1, 21, p<0.05), but also attenuated TG-evoked Ca2+ responses
      ([downward arrow]10% to [downward arrow]19%: F's=5.5-15.5, d.f.=1, 12, p's<0.05).
      However, chronic lamotrigine treatment did not affect LPA- or TG-stimulated Ca2+
      responses. These results suggest that chronic lithium and valproate treatments
      act differently from lamotrigine in respect of modulation of receptor- and/or
      capacitance-mediated Ca2+ flux. These differential effects on Ca2+ responses may
      be relevant to the distinctive clinical profiles of these mood stabilizers.

PMID- 19400979
TI  - Decreased GRK3 but not GRK2 expression in frontal cortex from bipolar disorder
      patients.
AB  - Overactivation of G-protein-mediated functions and altered G-protein regulation
      have been reported in bipolar disorder (BD) brain. Further, drugs effective in
      treating BD are reported to up-regulate expression of G-protein receptor kinase
      (GRK) 3 in rat frontal cortex. We therefore hypothesized that some G-protein
      subunits and GRK levels would be reduced in the brain of BD patients. We
      determined protein and mRNA levels of G-protein beta and gamma subunits, GRK2,
      and GRK3 in post-mortem frontal cortex from 10 BD patients and 10 age-matched
      controls by using immunoblots and real-time RT-PCR. There were statistically
      significant decreases in protein and mRNA levels of G-protein subunits beta and
      gamma and of GRK3 in BD brain but not a significant difference in the GRK2 level.
      Decreased expression of G-protein subunits and of GRK3 may alter
      neurotransmission, leading to disturbed cognition and behaviour in BD.

PMID- 19400981
TI  - Normalization of GRK2 protein and mRNA measures in patients with depression
      predict response to antidepressants.
AB  - G-protein-coupled receptor kinases (GRKs) interfere in receptor-G-protein
      coupling leading to desensitization of G-protein-mediated receptor signalling. G
      protein-coupled receptor signalling and its desensitization were previously
      implicated in the pathophysiology, diagnosis and treatment of mood disorders. The
      present study aimed to evaluate alterations in GRK2 protein and mRNA levels in
      mononuclear leukocytes (MNL) of untreated patients with major depression and the
      effects and time-course of antidepressant treatments on these alterations.
      Repeated GRK2 protein and mRNA measurements were carried in MNL of 24 patients
      with major depression. Each patient was examined while untreated and after 1, 2,
      3 and 4 wk of antidepressant treatment; 24 healthy subjects were also studied.
      GRK2 protein and mRNA levels were evaluated through immunoblot analyses using
      monoclonal antibodies against GRK2 and reverse transcriptase-polymerase chain
      reaction, respectively. GRK2 protein and mRNA levels in MNL of untreated patients
      with major depression were significantly lower than the measures characterizing
      healthy subjects. The decreased GRK2 protein and mRNA levels were alleviated by
      antidepressant treatment. Normalization of GRK2 measures preceded, and, thus,
      could predict clinical improvement by 1-2 wk. These findings support the
      implication of GRK2 in the pathophysiology of major depression and in the
      mechanism underlying antidepressant-induced receptor down-regulation and
      therapeutic effects. GRK2 measurements in patients with depression may
      potentially serve for biochemical diagnostic purposes and for monitoring and
      predicting response to antidepressants.

PMID- 19400982
TI  - Early induction of CREB activation and CREB-regulating signalling by
      antidepressants.
AB  - Converging evidence points to adaptive changes in neuroplasticity and gene
      expression as mediators of therapeutic action of antidepressants. Activation of
      cAMP response-element binding protein (CREB) and CREB-regulating signalling are
      considered main effectors in these mechanisms. We analysed the temporal profile
      of intracellular changes induced by antidepressants, by measuring activation of
      major CREB-regulating signalling cascades and activation (Ser133 phosphorylation)
      of CREB. The main aims of the study were to investigate how these different
      variables are modulated with time, whether stronger activation of signalling
      cascades corresponds to stronger activation of CREB, and whether these changes
      are different in distinct brain areas. Rat groups were treated for 1, 2 or 3 wk
      with the antidepressants fluoxetine or reboxetine; in additional groups drug
      treatment was followed by a washout week (3+1). Activation of CREB and major
      effectors in signalling cascades were analysed by Western blot analysis with
      phospho-antibodies, in nuclear and cytosolic fractions from hippocampus and
      prefrontal/frontal cortex (P/FC). Surprisingly, CREB activation was already
      maximal after 1-wk treatment. In hippocampus early and stronger CREB activation
      was consistent with early and stronger activation of signalling. For both drugs,
      the profile of activation in P/FC was different from that observed in
      hippocampus. The results also showed that, contrary to the activatory role of MAP
      ERKs and CaM kinase IV, nuclear alphaCaM kinase II was inactivated in parallel
      with activation of CREB.

PMID- 19400983
TI  - Neuregulin 1 hypomorphic mutant mice: enhanced baseline locomotor activity but
      normal psychotropic drug-induced hyperlocomotion and prepulse inhibition
      regulation.
AB  - Neuregulin 1 (Nrg1) has been widely recognized as a candidate gene for
      schizophrenia. This study therefore investigated mice heterozygous for a mutation
      in the transmembrane domain of this trophic factor (Nrg1+/- mice) in a number of
      behavioural test systems with relevance to schizophrenia, including psychotropic
      drug-induced locomotor hyperactivity and prepulse inhibition (PPI) of startle.
      Baseline locomotor activity in the open field or in photocell cages was slightly,
      but significantly enhanced in Nrg1+/- mice compared to wild-type littermate
      controls at age 12-16 wk, but not at age 6 months. The ability of amphetamine,
      phencyclidine (PCP) or MK-801 to induce locomotor hyperactivity was not
      significantly different between the genotypes. There was no difference in
      baseline PPI, startle or startle habituation and there was no difference in the
      effect of apomorphine, amphetamine or MK-801 on any of these parameters. Only
      treatment with the 5-HT1A receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH
      DPAT) showed a differential effect between genotypes, with a disruption of PPI
      occurring in Nrg1+/- mice compared to no effect in wild-type controls. This
      treatment also induced a significant reduction of startle which could have
      influenced the result. The density of dopamine D2 receptors in the forebrain and
      of 5-HT1A receptors in the hippocampus and raphe nuclei was not different between
      Nrg1+/- mice and controls. These studies add to the knowledge about behavioural
      effects in this mouse model of impaired Nrg1 function and suggest that a number
      of the behavioural tests with relevance to schizophrenia are normal in these
      mice.

PMID- 19400984
TI  - Pregnancies achieved by testicular sperm recovery in male hypogonadotrophic
      hypogonadism with persistent azoospermia.
AB  - Hypogonadotrophic hypogonadism is characterized by oligospermia or azoospermia
      and low testosterone, FSH and LH concentrations. In such cases, treatment with
      gonadotrophins is required to produce or increase spermatozoa in the ejaculate
      but few achieve normal spermatogenesis. After long periods of medical treatment,
      if the patients still have a low sperm count or azoospermia, assisted
      reproductive technologies in addition to hormone administration can be offered.
      Four cases of hypogonadotrophic hypogonadism with persistent azoospermia after at
      least 10 months of medical treatment are reported. In all four cases, spermatozoa
      retrieved by testicular sperm extraction and intracytoplasmic sperm injection
      (ICSI) were used to achieve fertilization. Excess spermatozoa were frozen in all
      cases. Six ICSI cycles using fresh testicular spermatozoa in four and thawed
      testicular spermatozoa in two were performed. Although there was no pregnancy in
      cycles where thawed spermatozoa were used, three clinical pregnancies were
      achieved in four cycles using fresh testicular spermatozoa. One of them ended
      with spontaneous abortion at 10 weeks of gestation and the two others resulted in
      the delivery of three normal offspring. If azoospermia persists after medical
      treatment, spermatozoa can be obtained surgically from testes and can be used
      successfully to achieve pregnancy in cases of hypogonadotrophic hypogonadism.

PMID- 19400985
TI  - Analysis of spermatogenesis in non-obstructive azoospermic and virtually
      azoospermic men with known testicular pathology.
AB  - It is widely thought that human testicles affected by unilateral pathology will
      have greater impairment of spermatogenesis than the otherwise unaffected testis.
      This study reviewed records of non-obstructive azoospermic (NOA) and virtually
      azoospermic (NOVA) men with associated testicular pathology who underwent
      testicular fine needle aspiration (FNA) mapping. Concentration of spermatozoa
      found in each testis was analysed to discern sperm-lateralization patterns in
      affected and unaffected testes. A total of 1098 FNA sites from 56 men (32
      varicocele, 16 cryptorchidism, three epididymo-orchitis, two mumps orchitis,
      three torsion) were analysed. Overall, 38 patients (68%) had spermatozoa detected
      in at least one testis. Most men (68%) had equal proportions of FNA sites showing
      spermatozoa from both testes, 29% had more spermatozoa from the unaffected testis
      and 3% had more spermatozoa from the affected testis. Significantly fewer sperm
      positive sites were observed on the affected (272 out of 752) than unaffected
      side (164 out of 346) (P < 0.0001, chi-squared test). When assessed by FNA
      mapping, most NOA and NOVA men with known unilateral testis pathology will have
      equal proportions of spermatozoa in both testes. However, when sperm production
      differs between sides, the unaffected side is much more likely to have
      spermatozoa. This information may be used to refine sperm-retrieval strategies in
      selected patients.

PMID- 19400986
TI  - A genetic survey of 1935 Turkish men with severe male factor infertility.
AB  - Male factor infertility is the sole reason in approximately 25% of couples who
      suffer from infertility. Genetic factors such as numerical and structural
      chromosomal abnormalities and microdeletions of the Y chromosome might be the
      cause of poor semen parameters. The results of karyotype analyses and Y
      chromosome microdeletions of 1935 patients with severe male factor infertility,
      which is the largest series from Turkey, were assessed retrospectively. The
      frequency of cytogenetic abnormalities among 1214 patients with non-obstructive
      azoospermia (NOA) and 721 patients with severe oligoasthenoteratozoospermia (OAT)
      were 16.40 and 5.83% respectively. The overall incidence of Y-chromosome
      microdeletion was 7.70%. The incidence of Y chromosome microdeletion in patients
      with NOA and OAT was 9.51 and 1.86% respectively. The abnormality rate increased
      with the severity of infertility. Some patients (n = 22) were carriers of both
      chromosomal abnormalities and Y-chromosome microdeletions. Results suggest the
      need for genetic screening and proper genetic counselling before initiation of
      assisted reproduction treatment.

PMID- 19400987
TI  - Separation of X- and Y-bearing human spermatozoa by sperm isolation medium
      gradients evaluated by FISH.
AB  - An eight-layer discontinuous sperm isolation medium (PureSperm gradient) was
      evaluated in separation of human spermatozoa according to sex chromosomes by
      fluorescence in-situ hybridization (FISH). This study was carried out on spare
      samples from normozoospermic and oligozoospermic patients referred to the Royan
      Institute for infertility treatment. Semen analysis was assessed according to
      World Health Organization criteria. X- and Y-bearing spermatozoa were
      simultaneously identified in the neat semen (control) and sperm isolation medium
      fractions from the same samples using FISH and chromosome specific DNA probes. At
      least 1000 spermatozoa were scored for each sample. The proportions of X- and Y
      bearing spermatozoa were determined by presence of red or green fluorescent
      signals. Before separation, there was no significant difference in the percentage
      of spermatozoa with the specific signals of X and Y chromosomes. After
      separation, in both normal and oligozoospermic patients, the percentage of X
      bearing spermatozoa in the bottom layer slightly exceeded that in the top layer
      (P = 0.001). In both the normal and oligozoospermic groups, the difference
      between the frequencies of Y-bearing spermatozoa in the top and bottom layers was
      significant (P = 0.001). It seemed that eight-step discontinuous gradient was not
      a reliable method for the separation X- and Y-bearing spermatozoa for clinical
      purposes.

PMID- 19400988
TI  - Correlation of sperm DNA damage with protamine deficiency in Iranian subfertile
      men.
AB  - To compare the extent of sperm DNA damage with the degree of protamine deficiency
      in spermatozoa of normal and subfertile individuals, 30 semen samples from three
      groups of subfertile individuals (oligozoospermic, asthenozoospermic and
      oligoasthenozoospermic) and 14 samples from normal individuals were collected
      from men referred to the Fertility and Infertility Centre of Shariati Hospital,
      Tehran. DNA damage was measured using the alkaline Comet assay, and protamine
      deficiency was measured using chromomycin A3 (CMA3) staining. Results indicated a
      significant difference in the extent of DNA damage in spermatozoa of subfertile
      patients compared with normal patients (P < 0.01). Spermatozoa from
      oligoasthenozoospermic patients showed a higher level of DNA damage compared with
      the other two study groups of subfertile men. The percentage of CMA3-positive
      spermatozoa was also higher in subfertile individuals compared with normal
      patients (P < 0.01), with the highest level occurring in oligoasthenozoospermic
      patients. A direct correlation between protamine deficiency and sperm DNA damage
      was found for all subfertile patients studied.

PMID- 19400989
TI  - Anomalies in sperm chromatin packaging: implications for assisted reproduction
      techniques.
AB  - Sperm protamine deficiency and DNA damage were analysed employing chromomycin
      A(3) (CMA(3)) staining and the terminal deoxynucleotidyl transferase-mediated
      dUTP nick-end labelling assay, respectively, in 132 patients (82 IVF, 50
      intracytoplasmic sperm injection [ICSI]). The antioxidant ability of seminal
      plasma was analysed in 10 men, using the total oxidant scavenging capacity assay.
      A significant negative correlation was found between abnormal protamination and
      sperm parameters, including sperm DNA fragmentation (P < 0.01). A close
      relationship was found between sperm protamination and fertilization and
      pregnancy only in IVF (P = 0.004 and P < 0.04, respectively); in ICSI there was a
      correlation between DNA fragmentation and pregnancy (P = 0.031). Finally, there
      was a negative correlation between chromatin under-protamination and the
      antioxidant ability of seminal plasma (P < 0.01). Results of this study underline
      that, despite sperm abnormal protamination and DNA fragmentation being positively
      correlated, they affect the reproductive outcome in different ways: in particular
      there was good prognostic value for CMA(3) analysis only in IVF, whereas DNA
      fragmentation analysis was prognostic only for ICSI outcome. Data are also
      provided to support the idea of a relationship between defective antioxidant
      system activity and impairment of chromatin packaging.

PMID- 19400990
TI  - Candida albicans experimental infection: effects on human sperm motility,
      mitochondrial membrane potential and apoptosis.
AB  - Studies suggest Candida albicans infection has a negative effect on sperm
      function, including fertilizing ability. Assisted reproduction treatment using
      spermatozoa from a patient with unrecognized C. albicans infection did not result
      in fertilization. Preliminary evidence suggested an effect on sperm motility and
      apoptosis. This study was undertaken to evaluate the effects of experimentally
      induced C. albicans infection on motility, membrane mitochondrial potential
      (MMP), chromatin packaging and apoptosis [membrane phosphatidylserine (PS)
      externalization and DNA fragmentation] of spermatozoa isolated from
      normozoospermic healthy men. Motile spermatozoa were isolated by swim-up from 13
      normal volunteers and exposed to increasing concentrations (0, 1000, 10,000, and
      100,000 cfu/ml) of the fungus for 3 and 24 h. C. albicans was isolated from
      vaginal swabs, after identification, freshly prepared for experiments. Following
      incubation, sperm motility decreased significantly (P < 0.05 from 10,000 cfu/ml)
      and spermatozoa with reduced MMP or PS externalization, an early sign of
      apoptosis, increased in a time- and concentration-dependent manner. Sperm DNA
      fragmentation and chromatin integrity increased slightly after exposure to C.
      albicans, but the increase did not reach statistical significance. This study
      showed that C. albicans infection may decrease the functional competence of
      spermatozoa by reducing motility and MMP and by promoting molecular apoptosis
      mechanisms.

PMID- 19400991
TI  - A large Northern European observational study of follitropin alpha filled-by-mass
      pre-filled pen.
AB  - This prospective observational post-marketing survey aimed at studying the
      efficacy and convenience of the follitropin alpha filled-by-mass (FbM) pre-filled
      pen for patients in routine use. These data were analysed among 3196 non-selected
      treatment cycles and couples in seven Northern European countries. Valuable
      information was also obtained regarding the routine assisted reproduction
      treatment protocols used in Northern Europe. Out of 3196 cycles, human chorionic
      gonadotrophin (HCG) was administered in 3104 (97.2%), and an embryo transfer was
      carried out in 2766 cycles (86.5%). A positive HCG was recorded in 997 cycles
      (31.2% per started cycle and 36.0% per embryo transfer). The overall clinical
      pregnancy rate was 23.1% (738/3196) and per embryo transfer it was 26.7%
      (738/2766), with a miscarriage rate of 3.4% (95/2766) per embryo transfer or 9.5%
      (95/997) per positive HCG. Among the 732 elective single embryo transfers (eSET),
      the rate of positive HCG was 38.0% and the clinical pregnancy rate was 29.6%,
      suggesting that eSET is a valuable option in routine assisted reproduction.
      Although minor differences were observed between countries, the follitropin alpha
      FbM pre-filled pen proved clinically effective, was generally well tolerated, and
      both the women and nurses/midwives found the training easy.

PMID- 19400992
TI  - Poor ovarian response to gonadotrophin stimulation is associated with FSH
      receptor polymorphism.
AB  - Similarities in the phenotype observed in women with FSH receptor mutation and in
      FSH receptor knockout mice have clearly established a critical role of this
      protein in normal gonadal function. Two common single nucleotide polymorphisms in
      the exonic region of the FSH receptor gene have been shown to be associated with
      altered ovarian response in subjects undergoing gonadotrophin treatment. Recent
      in-vitro studies have shown that the A allele at the -29 position in the 5
      untranslated region of the FSH receptor gene is associated with impaired
      transcriptional activity. Differential expression of the FSH receptor and its
      function may be one of the factors responsible for altered ovarian response.
      These observations prompted a study of the association between FSH receptor
      genotype at the -29 position and ovarian response in women undergoing
      gonadotrophin treatment. Analysis of the data revealed that the subjects with AA
      genotype at the -29 position required the highest amount of exogenous FSH for
      ovulation induction, and oestradiol concentrations before the day of human
      chorionic gonadotrophin administration were significantly lower (P = 0.015)
      compared with the GA genotype. The number of pre-ovulatory follicles and
      retrieved oocytes were lowest in the subjects with AA genotype. These results
      indicate that the AA genotype at position -29 may be associated with the poor
      ovarian response.

PMID- 19400994
TI  - Association of spindle midzone particles with polo-like kinase 1 during meiosis
      in mouse and human oocytes.
AB  - Polo-like kinase 1 (Plk1) has been reported to localize to the spindle midzone
      during meiosis in mouse oocytes. However, it has not been reported in human
      oocytes. In this study, the interaction of the meiotic structures and chromosome
      segregation in mouse and human oocytes were studied by time-lapse differential
      interference contrast microscopy. Using immunocytochemical studies, the
      localization of polo-like kinase 1 and its association with microtubules were
      examined during the extrusion of first and second polar bodies. It was found that
      Plk1 was localized in the spindle midzone in human oocytes at anaphase I and
      telophase I. Also, three-dimensional confocal laser microscopy showed that the
      meiotic spindle midzone contained numerous dot-like particles that were stained
      by anti-Plk1 antibody. These particles were aligned in the plane of the meiotic
      midzone in mouse and human oocytes.

PMID- 19400993
TI  - Ovulation induction using low-dose step-up rFSH in Vietnamese women with
      polycystic ovary syndrome.
AB  - The aim of this study was to assess the effectiveness and safety of a low-dose
      step-up protocol with a recombinant FSH starting dose of 25 IU for ovulation
      induction in anovulatory patients with polycystic ovary syndrome (PCOS) and a
      normal or low body mass index (BMI). In this prospective, non-comparative, open
      trial, 183 PCOS patients who had three unsuccessful cycles of ovulation induction
      with clomiphene citrate received recombinant FSH (Puregon((R))) 25 IU/day for 14
      days, the dose was then increased by 25 IU every 5 days if there was no follicle
      of >12 mm diameter (maximum 150 IU/day). Human chorionic gonadotrophin was
      administered when the lead follicle was >/=18 mm, and intrauterine insemination
      was performed 36 h later. Duration of stimulation was 15.9 +/- 4.8 days and total
      FSH dose was 484 +/- 257 IU. A developing follicle was observed in 96.7% of
      cycles, of which 62.1% had unifollicular development and 15.8% were cancelled due
      to over-response. The clinical and ongoing pregnancy rates were 35.5% and 33.9%,
      respectively. There were no multiple pregnancies, and only one case of mild
      ovarian hyperstimulation syndrome. A low-dose step-up protocol with a recombinant
      FSH starting dose of 25 IU/day is effective and safe in anovulatory Vietnamese
      PCOS patients with a low or normal BMI.

PMID- 19400995
TI  - Toxicity testing of human assisted reproduction devices using the mouse embryo
      assay.
AB  - Systems to assess the toxicity of materials used in human assisted reproduction
      currently lack efficiency and/or sufficient discriminatory power. The development
      of 1-cell CBA/B6 F1 hybrid mouse embryos to blastocysts, expressed as blastocyst
      rate (BR), is used to measure toxicity. The embryos were divided into control and
      test groups, and were exposed to either control medium or to a potentially toxic
      test medium. Inferences on toxicity were based on differences in BR between the
      two groups. The mouse embryo assay followed a stratified (mouse), randomized
      (embryo), and balanced (equal number of embryos per group and per mouse) design.
      The number of embryos needed was calculated using power analysis. The basal BR of
      the hybrid strain was determined in a historical population. Sixty-nine mouse
      embryos per group were required to detect toxic materials with sufficient
      sensitivity and to account for the considerable inter-mouse variation in
      blastocyst development. Fifty-two samples, divided over batches of seven
      different products were tested before use in the study IVF centre and five of
      these were found to be toxic. This test system, presented as the Nijmegen mouse
      embryo assay (NMEA), can be used to detect embryo-toxic materials in daily IVF
      practice, and this report may provide a starting point for standardization.

PMID- 19400996
TI  - Paternal contribution to aneuploidy in preimplantation embryos.
AB  - The association between sperm indices and the chromosomal status of
      preimplantation embryos was assessed in 230 couples with a female partner younger
      than 36 years undergoing 295 cycles of preimplantation diagnosis for aneuploidy:
      105 cycles had normozoospermic samples, 134 cycles presented with
      oligoasthenoteratozoospermia (OAT), while the remaining cycles had spermatozoa
      retrieved from the seminal tract due to obstructive (29 cycles) or non
      obstructive azoospermia (NOA, 27 cycles). One blastomere was biopsied from day-3
      embryos and analysed for chromosomes XY, 13, 15, 16, 17, 18, 21, and 22. From the
      testing of 1549 embryos, the proportion of chromosomally abnormal embryos was
      significantly lower in normozoospermic patients (55%) than in OAT (62%, P <
      0.025) and NOA patients (69%, P < 0.005). Complex abnormalities were the most
      frequent defect in NOA (68%), which also demonstrated the highest incidence of
      gonosomal aneuploidy (12%). From the re-analysis of all blastomeres in 493 non
      transferred embryos, 95% of NOA embryos were chaotic mosaics. In conclusion, a
      severe male infertility condition could contribute to the generation of
      chromosomal abnormalities in the resulting embryos. This might occur especially
      in NOA patients in which the high incidence of chromosomal abnormalities is
      mainly due to mosaicism and gonosomal aneuploidy.

PMID- 19400997
TI  - Chromosomal abnormalities and polymorphic variants in couples with repeated
      miscarriage in Mexico.
AB  - Cytogenetic studies have an important role in the evaluation of couples with
      repeated miscarriages and poor obstetric history. To estimate the prevalence of
      chromosomal abnormalities and polymorphic variants in 158 couples with repeated
      miscarriages, a cross-sectional study was conducted in Monterrey, Mexico from
      1995 to 2003. Peripheral blood lymphocytes were cultured for chromosomal studies
      using standard methods. Twelve couples showed chromosomal abnormalities (7.60%),
      two Robertsonian translocations (1.27%), two balanced translocations (1.27%), one
      inversion (0.63%), and one a novel insertion (0.63%). This insertion [46, XX, ins
      (15;8) (q26;p11p23)] is unique, and is the third reported in association with
      repeated abortion. Mosaicism was observed in six couples (3.80%, three with
      structural abnormalities and three with numerical abnormalities). A female to
      male ratio of 1.4:1 was observed. In addition to these chromosomal abnormalities,
      polymorphic variants in constitutive heterochromatin of the 1qh+, 9qh+, and 16qh+
      chromosomes were observed in 25 couples (15.82%), of the Yqh+ chromosome in 21
      couples (13.29%), and of satellite in 35 couples (22.15%). In conclusion,
      chromosome analysis is necessary for appropriate clinical management of these
      patients.

PMID- 19400998
TI  - Case report: Meiotic segregation in spermatozoa of a 46,X,t(Y;10)(q11.2;p15.2)
      fertile translocation carrier.
AB  - Translocations involving gonosomes are frequent in azoospermic patients and
      sometimes in oligozoospermic ones, conditions that lead to request for assisted
      reproduction treatment. This study reports an unexpectedly fertile 49-year-old
      man bearing a de-novo translocation 46,X,t(Y;10)(q11.2;q15.2) associated with a
      high chromosomal risk for offspring, and referred for familial investigations
      after the diagnosis of an unbalanced translocation
      46,XX,der(10)t(Y;10)(q11.2;p15.2) in his naturally conceived and mentally
      retarded daughter. Chromosome molecular investigation confirmed Y long-arm
      inheritance in the daughter and absence of the Yq deletion in the father. Semen
      analysis showed a normal sperm count associated with moderate asthenospermia and
      severe teratospermia. A total of 984 spermatozoa were analysed using fluorescence
      in-situ hybridization (FISH). Alternate segregation pattern was found in 50.31%
      of the spermatozoa studied. The frequencies of adjacent I, adjacent II, 3:1
      segregation, and diploidy (or 4:0 segregation) were respectively 39.62, 1.63,
      7.83, and 0.61%. No interchromosomal effect was observed. This patient is the
      first fertile man in whom the meiotic segregation pattern of a Y-autosome
      translocation has been analysed. The imbalance risk was close to those observed
      for reciprocal translocations, and emphasizes the value of FISH studies in males
      with a chromosomal translocation in order to provide them a personalized risk
      evaluation.

PMID- 19400999
TI  - Oestrogenic regulation and differential expression of WNT4 in the bonnet monkey
      and rodent epididymis.
AB  - A role for oestrogen in regulating fluid reabsorption in the monkey epididymis
      was recently demonstrated. Here, these studies are extended to identify potential
      oestrogen-regulated proteins in the cauda region of monkey epididymis treated
      with vehicle and oestrogen receptor antagonist (ICI 182780). Two-dimensional
      electrophoretic analysis was used to identify the proteins. The results indicated
      down-regulation of WNT4 in the ICI-182780-treated monkey cauda. In addition, the
      Wnt4 mRNA concentration was also reduced in the caput regions of ICI-182780-
      treated rats and oestrogen receptor knockout mice. WNT4 is a key regulator of
      gonadal differentiation in humans and mice and plays a pivotal role in early
      mouse embryogenesis. The results of the present study establish the presence of
      WNT4 in the monkey epididymis and its regulation by oestrogen, and suggest a role
      for WNT4 in maintaining epididymal homeostasis.

PMID- 19401000
TI  - Effects of cigarette smoke exposure on pregnancy outcome and offspring of
      diabetic rats.
AB  - A total of 52 female Wistar rats were distributed into four groups: non-diabetic
      (G1) and diabetic (G2) exposed to filtered air; non-diabetic (G3) and diabetic
      (G4) exposed to cigarette smoke. Diabetes was induced by streptozotocin (40 mg/kg
      bodyweight, i.v.). Rats were exposed, for 30 min, to filtered air (control) or to
      tobacco smoke generated from 10 cigarettes, twice a day, for 2 months. At the end
      of the 2-month exposure, at day 21 of pregnancy, each rat was anesthetized and
      humanely killed for laparotomy. Uterine horns were exposed for reproductive
      performance analysis, fetal and placental weights and placental index. Maternal
      and fetal data were analysed by ANOVA followed by the Student Newman-Keuls test.
      Fetal weight classification was assessed by Fisher's exact test. Diabetes and
      cigarette smoke caused placentomegaly (G4 = 0.65 +/- 0.19 g versus G1 = 0.49 +/-
      0.03 g, P < 0.05), increased placental index (G4 = 0.13 +/- 0.03 versus G1 = 0.09
      +/- 0.00, P < 0.05) and small fetus rates for pregnancy age (G4 = 88% versus G1 =
      23.2%, P < 0.05). These observations show the importance of encouraging pregnant
      women to attempt cessation of smoking.

PMID- 19401001
TI  - Successful vitrification of bovine and human ovarian tissue.
AB  - Ovariectomy and ovarian tissue cryopreservation has the potential to preserve the
      natural fertility of cancer patients prior to sterilizing chemo- and
      radiotherapies. Ovarian tissue cryopreservation with the conventional slow
      freezing method has yielded limited success, partly because of oocyte loss during
      freeze-thaw and subsequent transplant. Based on the high-efficiency vitrification
      Cryotop method, a practical vitrification procedure for murine, bovine and human
      ovarian tissue was developed. A Cryotissue method was designed for
      cryopreservation of ovarian tissue, and vitrification experiments were performed
      in a bovine animal model with ovarian size and structure similar to the human.
      There was no difference in oocyte viability (>89%) between fresh and vitrified
      ovarian cortical tissue in either bovine or human samples. Ovarian tissue was
      successfully autotransplanted to six cattle. Autotransplantation of vitrified
      warmed tissue back to the cattle resulted in no loss of oocyte viability. In
      addition, human ovarian tissue from cancer patients, and from ovary transplant
      donors was also vitrified by the Cryotissue method. After warming, high oocyte
      survival in human tissue (similar to bovine tissue) was obtained. These results
      indicate that an ultra-rapid cooling vitrification method has the potential for
      clinical use in human ovarian tissue cryopreservation.

PMID- 19401002
TI  - Case report: Successful IVF programme after conservatively treated endometrial
      cancer.
AB  - Some cases of successful pregnancy after conservative endometrial cancer
      management have been reported. This paper presents such a case, an infertile
      patient with conservatively treated endometrial cancer (stage 1a grade 1) who
      conceived and carried a successful pregnancy after IVF treatment. The
      conservative treatment consisted of hysteroscopic biopsies and oral megestrol
      acetate 600 mg daily for 3 months. At the end of the treatment the endometrial
      cancer remitted to simple endometrial hyperplasia. IVF was performed immediately
      and 32 days after embryo transfer an intrauterine single gestational sac with
      fetal pole and heartbeat was detected by transvaginal ultrasound. The woman
      received routine obstetric care and a caesarean section was performed at 38 weeks
      of gestation. The histological evaluation after delivery showed no evidence of
      recurrent disease. Twenty-six months after the delivery, the woman is healthy and
      free of the disease. It is concluded that conservative treatment of stage 1a and
      grade 1 endometrial adenocarcinoma is an available option in young women who wish
      to preserve their fertility.

PMID- 19401003
TI  - IVF outcome in women with endometriosis in relation to tumour necrosis factor and
      anti-Mullerian hormone.
AB  - This study reports on anti-Mullerian hormone (AMH) in serum and follicular fluid
      (FF) in relation to inflammatory parameters in women with and without
      endometriosis undergoing IVF. Serum and FF samples were obtained from 72 women,
      with (n = 34) and without (n = 38) endometriosis, undergoing IVF. The
      concentrations of AMH, FSH, tumour necrosis factor (TNF), granulocyte-macrophage
      colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) and
      several interleukins were analysed. Women with endometriosis had significantly
      lower AMH in serum and FF (serum: 6.38 versus 12.8 pM; P < 0.01, FF: 14.0 versus
      19.6 pM; P < 0.05). TNF was increased in FF (40.0 versus 30.8 pg/ml, P < 0.05)
      from women with endometriosis and significantly higher concentrations of IL-15
      and GM-CSF were detected in FF (both P < 0.05). During IVF, women with
      endometriosis responded well to FSH but had lower fertilization rates. Women with
      endometriosis have elevated concentrations of several cytokines in FF. They
      respond adequately to exogenous FSH but may have impaired oocyte quality,
      reflected in lower fertilization rates, presumably resulting from an inflammatory
      process in the ovaries. Further studies are needed to elucidate the role of AMH
      in predicting ovarian reserve in women with endometriosis.

PMID- 19401004
TI  - That by which it is what it is.

PMID- 19401005
TI  - Getting a grip on guidelines: how to make them more relevant for practice.

PMID- 19401006
TI  - Direct access to diagnostic services.

PMID- 19401007
TI  - Cell-free fetal DNA and non-invasive prenatal diagnosis.

PMID- 19401008
TI  - How could depression guidelines be made more relevant and applicable to primary
      care? A quantitative and qualitative review of national guidelines.
AB  - BACKGROUND: Many guidelines have been developed in the area of depression but
      there has been no systematic assessment of their relevance to general practice.
      AIM: To assess national guidelines on general practice management of depression
      using two complementary approaches to identify specific ways in which guidance
      could be made more relevant and applicable to the nature of general practice and
      the patients who seek help in this context. DESIGN OF STUDY: Review of national
      guidelines. SETTING: Seven English speaking countries: UK, US, Australia, New
      Zealand, Ireland, Canada, and Singapore. METHOD: Seven guidelines were
      independently reviewed quantitatively using the Appraisal of Guidelines for
      Research and Evaluation (AGREE) scores and qualitatively using thematic coding.
      RESULTS: The quantitative assessment highlights that most of the guidelines fail
      to meet the criteria on rigour of development, applicability, and editorial
      independence. The qualitative assessment shows that the majority of guidelines do
      not address associated risk factors sufficiently and the dilemma of diagnostic
      uncertainty flows over into management recommendations. Management strategies for
      depression (antidepressants and psychological strategies) are supported by all of
      the guidelines, with several listing drugs before psychological therapies; there
      is limited attention paid to the different types of psychological therapies.
      Moreover, the guidelines in the main fail to acknowledge individual patient
      circumstances, in particular the influence on response to treatment of social
      issues such as adverse life events or social support. CONCLUSION: Assessments of
      current national guidelines on depression management in general practice suggest
      significant limitations in their relevance to general practice.

PMID- 19401009
TI  - Weight-management interventions in primary care: a pilot randomised controlled
      trial.
AB  - BACKGROUND: There is a paucity of randomised controlled trials of weight
      management in primary care. AIM: To ascertain the feasibility of a full trial of
      a nurse-led weight-management programme in general practice. DESIGN OF STUDY:
      Factorial randomised control trial. SETTING: Primary care, UK. METHOD: A total of
      123 adults (80.3% women, mean age 47.2 years) with body mass index > or =27
      kg/m(2), recruited from eight practices, were randomised to receive structured
      lifestyle support (n = 30), structured lifestyle support plus pedometer (n = 31),
      usual care (n = 31), or usual care plus pedometer (n = 31) for a 12-week period.
      RESULTS: A total of 103 participants were successfully followed up. The adjusted
      mean difference in weight in structured support compared to usual care groups was
      -2.63 kg (95% confidence interval [CI] = -4.06 to -1.20 kg), and for pedometer
      compared to no pedometer groups it was -0.11 kg (95% CI = -1.52 to 1.30 kg). One
      in three participants in the structured-support groups (17/50, 34.0%) lost 5% or
      more of their initial weight, compared to less than one in five (10/53, 18.9%) in
      usual-care groups; provision of a pedometer made little difference (14/48, 29.2%
      pedometer; 13/55, 23.6% no pedometer). Difference in waist circumference change
      between structured-support and usual-care groups was -1.80 cm (95% CI = -3.39 to 
      0.20 cm), and between the pedometer and no pedometer groups it was -0.84 cm (95%
      CI = -2.42 to 0.73 cm). When asked about their experience of study participation,
      most participants found structured support helpful. CONCLUSION: The structured
      lifestyle support package could make substantial contributions to improving
      weight-management services. A trial of the intervention in general practice is
      feasible and practicable.

PMID- 19401010
TI  - Distilling the essence of general practice: a learning journey in progress.
AB  - Over the past 5 years, general practice in the UK has undergone major change.
      Starting with the introduction of the new GMS contract in 2004, it has continued
      apace with the establishment of Postgraduate Medical Education Training Board, a
      GP training curriculum, and nMRCGP. The NHS is developing very differently in the
      four countries of the UK. Regulation of the profession is under review, and a
      system of relicensing, recertification, and revalidation is being introduced. The
      Essence project, initiated by RCGP Scotland in conjunction with International
      Futures Forum 4 years ago is a constructive response to these changes. It has
      included learning journeys, a discussion day for GPs, and commissioned short
      pieces of 100 words from GPs and patients. From an analysis of these, some
      characteristics of the essence of general practice have been defined. These
      include key roles and core personal qualities for GPs. It is argued that general
      practice has important and unique advantages - trust, coordination, continuity,
      flexibility, universal coverage, and leadership - which mean that it should
      continue to be central to the development of primary care throughout the UK.

PMID- 19401011
TI  - Commentary: distributed intelligence--a different model for primary care.

PMID- 19401012
TI  - Commentary: unintended consequences: what of quality outside the QOF?

PMID- 19401013
TI  - Frailty: an emerging concept for general practice.
AB  - Ageing of the population in western societies and the rising costs of health and
      social care are refocusing health policy on health promotion and disability
      prevention among older people. However, efforts to identify at-risk groups of
      older people and to alter the trajectory of avoidable problems associated with
      ageing by early intervention or multidisciplinary case management have been
      largely unsuccessful. This paper argues that this failure arises from the
      dominance in primary care of a managerial perspective on health care for older
      people, and proposes instead the adoption of a clinical paradigm based on the
      concept of frailty. Frailty, in its simplest definition, is vulnerability to
      adverse outcomes. It is a dynamic concept that is different from disability and
      easy to overlook, but also easy to identify using heuristics (rules of thumb) and
      to measure using simple scales. Conceptually, frailty fits well with the
      biopsychosocial model of general practice, offers practitioners useful tools for
      patient care, and provides commissioners of health care with a clinical focus for
      targeting resources at an ageing population.

PMID- 19401015
TI  - Open Access Tubal aSsessment for the initial management of infertility in general
      practice (the OATS trial): a pragmatic cluster randomised controlled trial.
AB  - BACKGROUND: GPs investigate approximately half of all infertile couples with
      semen analysis and endocrine blood tests. For assessment of tubal status,
      hysterosalpingography (HSG) is recommended as a first-line investigation for
      women not known to have comorbidities. AIM: To test whether providing GPs with
      open access to HSG results in infertile couples progressing to a diagnosis and
      management plan sooner than with usual management. DESIGN OF STUDY: A pragmatic
      cluster randomised controlled trial. SETTING: Seventy-one of 173 general
      practices in north-east England agreed to participate. METHOD: A total of 670
      infertile couples presented to 33 intervention practices and 25 control practices
      over a 2-year period. Practices allocated to the intervention group had access to
      HSG for those infertile women who fulfilled predefined eligibility criteria. The
      primary outcome measure was the interval between presentation to the GP and the
      couple receiving a diagnosis and management plan. RESULTS: An annual incidence of
      0.8 couples per 1000 total population equated to each GP seeing an average of one
      or two infertile couples each year. Open access HSG was used for 9% of all
      infertile women who presented to the intervention practices during the study
      period. The time to reach a diagnosis and management plan for all infertile
      couples presenting was not affected by the availability of open access HSG (Cox
      regression hazard ratio = 0.9, 95% confidence interval [CI] = 0.7 to 1.1). For
      couples who reached a diagnosis and management plan, there was a non-significant
      difference in time to primary outcome for intervention versus control practices
      (32.5 weeks versus 30.5 weeks, mean difference 2.2 weeks, 95% CI = 1.6 to 6.1
      weeks, P = 0.1). The intracluster correlation coefficient was 0.03 across all
      practices. CONCLUSION: Providing GPs with open access to HSG had no effect on the
      time taken to reach a diagnosis and management plan for couples with infertility.

PMID- 19401016
TI  - Patient and professional views of open access hysterosalpingography for the
      initial management of infertility in primary care.
AB  - BACKGROUND: Hysterosalpingography (HSG) is recommended as a first-line
      investigation for tubal assessment of infertile women. This investigation is not
      routinely available to GPs. AIM: To explore the perceptions and attitudes of
      patients and health professionals to open access HSG for the initial management
      of infertile couples in general practice. DESIGN OF STUDY: A nested qualitative
      study using in-depth interviews with GPs, fertility specialists, and infertile
      couples. SETTING: Northumberland, Newcastle upon Tyne, North Tyneside, South
      Tyneside, and Gateshead. METHOD: Participants were 39 interviewees: 12 GPs, five
      fertility specialists, and 13 infertile couples (nine interviewed with their
      partner). RESULTS: Four themes emerged: personal factors; will it benefit
      patients, GPs, and fertility specialists?; professional factors; does it fit the
      role of a GP?; local context; do the skills exist in general practice?; and wider
      context; will it benefit the NHS? GPs who had used open access HSG, felt it was
      appropriate for general practice and would continue to use the service. All GPs,
      fertility specialists, and infertile couples who had experienced open access HSG
      wished the service to remain in place. The main barriers to its uptake were:
      infrequency with which infertility presents; lack of clarity on perceived
      responsibilities; difficulty keeping up to date, including assimilating
      guidelines; low clinical priority; and lack of support in authoritative guidance.
      CONCLUSION: Providing GPs with open access to HSG would allow a full initial
      assessment of the infertile couple and refer women with blocked tubes directly to
      tertiary care. While there is general support for the provision of such a
      facility, the majority of GPs perceive its use as being by a limited number of
      GPs who have a special interest in infertility. The study findings can inform
      future development of infertility services at the interface between primary and
      secondary/tertiary care.

PMID- 19401017
TI  - Presentation and outcome of clinical poor performance in one health district over
      a 5-year period: 2002-2007.
AB  - BACKGROUND: The detection, assessment, and management of primary care poor
      performance raise difficult issues for all those involved. Guidance has largely
      focused on managing the most serious cases where patient safety is severely
      compromised. The management of primary care poor performance has become an
      increasingly important part of primary care trust (PCT) work, but its modes of
      presentation and prevalence are not well known. AIM: To report the prevalence,
      presentation modes, and management of primary care poor performance cases
      presenting to one PCT over a 5-year period. DESIGN OF STUDY: A retrospective
      review of primary care poor performance cases in one district. SETTING: St Helens
      PCT administered 35 practices with 130 GPs on the performers list, caring for 190
      110 patients in North West England, UK. METHOD: Cases presenting during 2002-2007
      were initially reviewed by the chair of the PCT clinical executive committee.
      Anonymised data were then jointly reviewed by the assessor and another
      experienced GP advisor. RESULTS: There were 102 individual presentations (20 per
      year or one every 2-3 weeks) where clinician performance raised significant cause
      for concern occurred over the 5-year period. These concerns related to 37
      individual clinicians, a range of 1-14 per clinician (mean 2.7). Whistleblowing
      by professional colleagues on 43 occasions was the most common presentation, of
      which 26 were from GPs about GPs. Patient complaints (18) were the second most
      common presentation. Twenty-seven clinicians were GPs, of whom the General
      Medical Council (GMC) were notified or involved in 13 cases. Clinicians were
      supported locally, and remedying was exclusively locally managed in 14 cases, and
      shared with an external organisation (such as the GMC or deanery) in another 12.
      CONCLUSION: Professional whistleblowing and patient complaints were the most
      common sources of presentation. Effective PCT teams are needed to manage
      clinicians whose performance gives cause for concern. Sufficient resources and
      both formal and informal ways of reporting concerns are essential.

PMID- 19401018
TI  - Improving the sensitivity of the Dutch guidelines for case finding in
      osteoporosis.

PMID- 19401019
TI  - Travelling in Palestine.

PMID- 19401020
TI  - A fractured service: will NOGG mend it?

PMID- 19401021
TI  - How much should a GP read?

PMID- 19401022
TI  - GP investigators.

PMID- 19401023
TI  - GPs as investigators.

PMID- 19401024
TI  - A snapshot of general practice in Europe.

PMID- 19401025
TI  - Is there an elephant in the room?

PMID- 19401027
TI  - Is CAMHS suitable for a GP training placement?

PMID- 19401028
TI  - Treating autism appropriately.

PMID- 19401029
TI  - The rise of the medical McJob: why we should turn the clock back.

PMID- 19401031
TI  - Why GPs should write case reports.

PMID- 19401032
TI  - A rose by any other name.

PMID- 19401033
TI  - Cigarette smoke exposure impairs respiratory epithelial ciliogenesis.
AB  - BACKGROUND: Cigarette smoke exposure is considered an important negative
      prognostic factor for chronic rhinosinusitis (CRS) patients. However, there is no
      clear mechanistic evidence implicating cigarette smoke exposure in the poor
      clinical evolution of the disease or in the maintenance of the inflammatory state
      characterizing CRS. This study aimed to evaluate the effects of cigarette smoke
      exposure on respiratory cilia differentiation. METHODS: Mouse nasal septal
      epithelium cultures grown at an air-liquid interface were used as a model of
      respiratory epithelium. After 5 days of cell growth, cultures were exposed to air
      on the apical surface. Additionally, cigarette smoke condensate (CSC; the
      particulate phase of tobacco smoke) or cigarette smoke extract (CSE; the volatile
      phase) were diluted in the basolateral compartment in different concentrations.
      After 15 days of continuous exposure, scanning electron microscopy and
      immunofluorescence for type IV tubulin were used to determine presence and
      maturation of cilia. Transepithelial resistance was also recorded to evaluate
      confluence and physiological barrier integrity. RESULTS: CSC and CSE impair
      ciliogenesis in a dose-dependent manner with notable effects in concentrations
      higher than 30 microg/mL, yielding >70% nonciliation and shorter cilia compared
      with control. No statistical difference on transepithelial resistance was
      evident. CONCLUSION: CSC and CSE exposure negatively impacts ciliogenesis of
      respiratory cells at concentrations not effecting transepithelial resistance. The
      impairment on ciliogenesis reduces the mucociliary clearance apparatus after
      injury and/or infection and may explain the poor response to therapy for CRS
      patients exposed to tobacco smoke.

PMID- 19401034
TI  - Immunomodulatory effect of cytosine-phosphate-guanosine (CpG)-oligonucleotides in
      nonasthmatic chronic rhinosinusitis: an explant model.
AB  - BACKGROUND: The use of cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG
      ODNs) or immunostimulatory sequences (ISSs) in the treatment of airway diseases
      is gaining interest. Binding of the CpG-ODN ligand to Toll-like receptor 9 (TLR9)
      triggers a shift from a Th2- to a Th1-type response in the target tissue. In this
      study, we explored the potential use of CpG-ODN to dampen the predominantly Th2
      driven chronic inflammatory state in our cohort of patients. METHODS: An in vitro
      explant model comprising of sinonasal tissue from patients with asthma (n = 12)
      and without asthma (n = 11) were stimulated with CpG-ODN or Staphylococcus aureus
      enterotoxin B (SEB) or CpG-ODN in combination with SEB for 48 hours. Ten of the
      12 asthma patients had nasal polyps. RNA was extracted for multiplex real-time
      reverse transcription polymerase chain reaction analysis and the 2(-delta
      deltaC(T)) method used to determine interleukin (IL)-5, p35 IL-12, interferon
      (IFN) gamma, and TLR9 expression levels. RESULTS: CpG-ODN significantly reduced
      IL-5 mRNA expression in patients without asthma (p = 0.0379) but not in the
      asthma-associated group. SEB alone caused an increase in IL-5 levels that could
      be dampened when CpG-ODN was added in combination with SEB. Significant
      differences in mean IL-5 expression levels between the asthmatic and nonasthmatic
      categories were detected (Welch t-test; **p = 0.0041). Asthmatic and nonasthmatic
      patients present as two distinct categories as reflected by significant
      differences in their IL-5 response to CpG-ODN (F = 11.93; ***p = 0.0008), SEB (F
      = 41.34; *p = 0.0476) and CpG-ODN with SEB (F = 13.2; *p = 0.0114). In contrast,
      no significant differences were observed in the expression levels of IL-12, IFN
      gamma, and TLR9. CONCLUSION: Localized application of CpG-ODN on its own or in
      combination with SEB may potentially reduce the expression of the proinflammatory
      cytokine IL-5 in nonasthmatic patients and may be further developed as an
      immunotherapeutic agent.

PMID- 19401035
TI  - Up-regulation of heparanase in the ethmoid sinus mucosa of patients with chronic
      sinusitis.
AB  - BACKGROUND: Heparanase (HPA) is known to be involved in tissue remodeling of
      various organs with inflammatory diseases. The aim of this study was to
      investigate the level of expression and the pattern of distribution of HPA in
      normal human sinus mucosa, inflammatory sinus mucosa, and nasal polyps to
      evaluate the possible effect of HPA on the tissue remodeling of chronic
      inflammatory sinus mucosa and nasal polyps. METHODS: Normal sinus mucosa was
      obtained from the ethmoid sinus during endoscopic reduction in 25 patients with
      blowout fractures. Inflammatory sinus mucosa and nasal polyps were obtained from
      25 patients undergoing endoscopic sinus surgery for chronic sinusitis with nasal
      polyps. The levels of expression and the pattern of distribution of HPA were
      evaluated in normal human sinus mucosa, inflammatory sinus mucosa, and nasal
      polyps, using reverse transcriptase-polymerase chain reaction,
      immunohistochemical analysis, and Western blot analysis. RESULTS: HPA mRNA and
      protein were detected in inflammatory sinus mucosa and nasal polyps but not in
      normal sinus mucosa. HPA was mainly localized in the vascular endothelium,
      epithelium, submucosal glands, and inflammatory cells of inflammatory sinus
      mucosa. In nasal polyps, inflammatory cells and vascular endothelium showed
      immunopositivity in the entire portion, whereas glands and epithelial cells did
      not show positivity. CONCLUSION: Our results indicate that HPA is not
      constitutively expressed in normal sinus mucosa and is upregulated in chronic
      inflammatory sinus mucosa and nasal polyps, suggesting that HPA may play an
      important role in the tissue remodeling in chronic sinusitis.

PMID- 19401036
TI  - Prolactin may stimulate proliferation in the olfactory epithelium of the female
      mouse.
AB  - BACKGROUND: Although it is well known that olfactory receptor neurons
      differentiated from stem cells have an unusual lifelong ability to continue
      neurogenesis, effective treatment of patients with sensorineural olfactory loss
      is still lacking. The purpose of this study was to determine whether intranasal
      prolactin (PRL) is an effective inducer of proliferation in the olfactory
      epithelium (OE). METHODS: The OE of mice treated with PRL for 6 consecutive days
      and of pregnant mice on gestation day (GD) 7 was investigated by
      immunohistochemical study using antibodies to bromodeoxyuridine. RESULTS: The
      number of bromodeoxyuridine -labeled cells in the OE increased significantly in
      PRL-treated female mice and GD 7 mice (but not PRL-treated male mice) compared
      with controls. CONCLUSION: Pregnancy may induce proliferation in the OE, and
      administration of intranasal PRL may have almost the same effect as pregnancy on
      the OE of female mice.

PMID- 19401037
TI  - Olfactory function and disease severity in chronic rhinosinusitis.
AB  - BACKGROUND: Olfactory dysfunction is deemed to be a significant contributor to
      poor quality of life (QOL). However, little is known about the relationship of
      olfactory testing to other measures of disease burden in patients with chronic
      rhinosinusitis (CRS). In this study, we examine the relationship of olfactory
      function to computed tomography (CT) scores, endoscopy scores, and QOL measures
      in patients with CRS. METHODS: A multi-institutional, cross-sectional analysis of
      367 patients was performed. Several objective measures were collected: the Smell
      Identification Test, Lund-MacKay CT score, Lund-Kennedy endoscopy score, two
      validated disease-specific QOL instruments, the Rhinosinusitis Disability Index
      and the Chronic Sinusitis Survey, and a general health-related QOL instrument,
      the Medical Short Form-36. Analysis of variance was performed. Correlation
      coefficients were calculated. RESULTS: Patients with olfactory dysfunction had
      significantly worse mean endoscopy scores (normosmics, 4.16 [+/- 3.97];
      hyposmics, 6.26 [+/- 4.21]; anosmics, 9.61 [+/- 4.48]; p < 0.001) and
      significantly worse CT scores (normosmics, 9.11 [+/- 5.40]; hyposmics, 11.16 [+/-
      5.96]; anosmics, 17.62 [+/- 5.37]; p < 0.001). Endoscopy scores were moderately
      correlated with olfactory scores (r = -0.46; 95% CI, -0.38, -0.54; p < 0.001). CT
      scores were moderately correlated with olfactory scores (r = -0.53; 95% CI, 
      0.45, -0.60; p < 0.001). Olfactory function was not correlated with disease
      specific or general health-related QOL measures. CONCLUSION: Although previous
      studies have suggested that olfactory impairment is associated with poor QOL,
      this study found no such correlation. In contrast, olfaction scores correlated
      well with other objective measures of CRS, namely, endoscopy and CT scores.

PMID- 19401038
TI  - Relationships between severity of chronic rhinosinusitis and nasal polyposis,
      asthma, and atopy.
AB  - BACKGROUND: The effect of comorbid conditions such as asthma and atopy on the
      severity of chronic rhinosinusitis (CRS) and the presence of nasal polyps (NPs)
      remains an area of investigation. We sought to elucidate the relationship among
      these entities. METHODS: The study population included 106 consecutive patients
      who were referred to a multidisciplinary, university-based allergy and sinus
      clinic that underwent computed tomography (CT) scan, skin-prick testing, and had
      CRS. Data were analyzed to determine Lund-MacKay score (LMS), presence of NPs,
      asthma status, and sensitivity to seven classes of aeroallergens. RESULTS: Skin
      tests were positive in 52 cases and negative in 54 cases. Although, there was no
      statistical relationship between LMS and atopic status in the entire group, among
      the asthmatic subgroup, mean LMS was greater in nonatopic asthmatic patients than
      in atopic asthmatic patients. Asthmatic patients had a higher LMS than
      nonasthmatic patients (p < 0.0001). Asthmatic patients were more likely than
      nonasthmatic patients to have NPs (57.6% versus 25%; p = 0.0015), regardless of
      atopic status. Mean LMS was higher in NP patients compared with nonpolyp patients
      (p < 0.0001), independent of atopic status. Mean LMS was not affected by
      sensitivity to any particular allergen, with the exception of cockroach-allergic
      patients who were more likely to have an LMS of >10 (p = 0.0236) and had more
      severe maxillary sinus involvement (p = 0.0391). CONCLUSION: These data indicate
      a strong relationship between CRS severity, as measured by LMS, and chronic
      airway inflammatory diseases, asthma, and NPs. The association between LMS and
      atopic status appears weak. The present study suggests that CRS is an
      inflammatory disease that occurs independently of systemic IgE-mediated pathways.

PMID- 19401039
TI  - Comparison of vectorial ion transport in primary murine airway and human
      sinonasal air-liquid interface cultures, models for studies of cystic fibrosis,
      and other airway diseases.
AB  - BACKGROUND: The purpose of this study was to compare vectorial ion transport
      within murine trachea, murine nasal septa, and human sinonasal cultured
      epithelium. Our hypothesis is that murine septal epithelium, rather than trachea,
      will more closely mimic the electrophysiology properties of human sinonasal
      epithelium. METHODS: Epithelium from murine trachea, murine septa, and human
      sinonasal tissue were cultured at an air-liquid interface to confluence and full
      differentiation. A limited number of homozygous dF508 epithelia were also
      cultured. Monolayers were mounted in modified Ussing chambers to investigate
      pharmacologic manipulation of ion transport. RESULTS: The change in forskolin
      stimulated current (delta-I(SC), expressed as micro-A/cm(2)) in murine septal (n
      = 19; 16.84 +/- 2.09) and human sinonasal (n = 18; 12.15 +/- 1.93) cultures was
      significantly increased over murine tracheal cultures (n = 15; 6.75 +/- 1.35; p =
      0.035 and 0.0005, respectively). Forskolin-stimulated I(SC) was inhibited by the
      specific cystic fibrosis transmembrane regulator (CFTR) inhibitor INH-172 (5
      microM). No forskolin-stimulated I(SC) was shown in cultures of dF508 homozygous
      murine septal epithelium (n = 3). Murine septal I(SC) was largely inhibited by
      amiloride (12.03 +/- 0.66), whereas human sinonasal cultures had a very limited
      response (0.70 +/- 0.47; p < 0.0001). The contribution of CFTR to stimulated
      chloride current as measured by INH-172 was highly significantly different
      between all groups (murine septa, 19.51 +/- 1.28; human sinonasal, 11.12 +/-
      1.58; murine trachea, 4.85 +/- 0.49; p < 0.0001). CONCLUSION: Human sinonasal and
      murine septal epithelial cultures represent a useful model for studying CFTR
      activity and may provide significant advantages over lower airway tissues for
      investigating upper and lower respiratory pathophysiology.

PMID- 19401040
TI  - Changes of airflow pattern in inferior turbinate hypertrophy: a computational
      fluid dynamics model.
AB  - BACKGROUND: Nasal obstruction (NO) is a very common symptom, but its effect on
      nasal physiology has not been fully understood. We performed this study to
      determine the effect of severity of NO due to inferior turbinate hypertrophy on
      airflow pattern using the computational fluid dynamics simulations. METHODS: A
      three-dimensional nasal cavity model was constructed from the MRI scans of a
      healthy human subject. Nasal cavities corresponding to healthy, moderate, and
      severe NO was simulated by enlarging the inferior turbinate geometrically, which
      can be documented by approximately one-third reduction of the minimum cross
      sectional area (1.453 cm(2) in the healthy nose) for the moderate (0.873 cm(2))
      and two-thirds (0.527 cm(2)) for the severe obstruction. RESULTS: Total negative
      pressure through the nasal cavity increased during the inspiratory phase by
      almost twofold (-19 Pa) and threefold (-33 Pa) for moderate and severe blockage,
      respectively, compared with the increase of total negative pressure of -10 Pa in
      a healthy nose. In cases of moderate and severe blockage, a higher velocity and
      shear stress was observed at the nasopharynx and dorsal region of the nasal
      cavity. Moreover, nasal valve function will not exist in severe NO because of the
      changes of airflow pattern at the original nasal valve location. CONCLUSION:
      Impairment of nasal airflow and physiology is evidenced in NO caused by inferior
      turbinate hypertrophy. Data of this study may help in predicting the aerodynamic
      effects of surgical correction of the inferior turbinate hypertrophy.

PMID- 19401041
TI  - Nitric oxide metabolites as biomarkers for follow-up after chronic rhinosinusitis
      surgery.
AB  - BACKGROUND: Nitric oxide (NO) has a variety of effects on the pathophysiology of
      the nasal cavity and seems to play an important role in inflammation. It is
      increased in the common cold but decreased in acute and chronic rhinosinusitis
      (CRS). Exhaled NO increases after endoscopic sinus surgery in CRS. In our
      previous study we showed that NO metabolite (nitrate and nitrite) levels are
      increased in the sinus cavity of CRS patients. We hypothesized that NO metabolite
      levels are increased to normal in the nasal lavage of CRS patients after
      endoscopic sinus surgery and NO metabolites in the nasal lavage can be used as
      indicators of the disease status after surgery. METHODS: This study was performed
      on 52 patients with CRS who did not respond to medical therapy and who underwent
      surgery. NO metabolite levels were measured in nasal lavages of the patients
      before surgery and 2 months after surgery. RESULTS: NO metabolite levels (mean +/
      SEM) were 18.11 +/- 3.08 micromol/L and 35.97 +/- 4.64 micromol/L in nasal
      lavages of patients before and after surgery, respectively. The levels of NO
      metabolites were increased significantly (p < 0.01) after surgery in nasal
      lavages and patients reported significant improvement based on the visual analog
      scoring after the operation. CONCLUSION: NO metabolite levels were decreased in
      nasal lavages of CRS patients and were increased to normal levels after surgery
      along with improvement of the disease. NO metabolite levels may be used as an
      indicator for the follow-up of patients after endoscopic sinus surgery.

PMID- 19401042
TI  - Low temperature results in decreased tension in decellularized human nasal
      mucosa.
AB  - BACKGROUND: Cooling may induce nasal obstruction. In our previous study, we
      showed low temperature induced a rapid relaxation of isolated human nasal mucosa
      and it was independent of vasoconstriction. The aim of this study was to
      elucidate the mechanism responsible for such findings. METHODS: Nasal mucosa
      strips were prepared from inferior turbinate samples. Decellularization of human
      nasal mucosa was achieved by treatment with sodium dodecyl sulfate 0.1% for 15
      hours at 37 degrees C in a shaking water bath. Then, the effect of cooling (37-10
      degrees C) on the isometric tension change of decellularized nasal mucosa was
      evaluated. In addition, the presence of elastic fibers within the nasal mucosa
      was identified in both histological section and scanning electron microscope.
      RESULTS: Results indicated cooling induced a relaxation response of isolated
      decellularized human nasal mucosa and it was similar to that of intact nasal
      mucosa. The elastic fibers formed in wavy lines and were distributed throughout
      the submucosal layer. CONCLUSION: Cooling induced a similar relaxation response
      both in the absence or in the presence of cellular components in isolated human
      nasal mucosa, suggesting that this response is mediated by the abundant
      extracellular matrix.

PMID- 19401043
TI  - Sternberg's canal: fact or fiction?
AB  - BACKGROUND: Sternberg's (lateral craniopharyngeal) canal was originally described
      in anatomic studies as a membranous space in the lateral wall of the sphenoid
      sinus. The canal has been etiologically associated with lateral sphenoid sinus
      "spontaneous" cerebrospinal fluid (CSF) leaks. A patent Sternberg's canal has
      been reported in up to 4% of adults, and persistent vestiges have been reported
      in up to 30%. However, no modern studies analyzing high-resolution CT scans have
      been published. METHODS: A consecutive analysis of 1000 high-resolution CT scans
      of sphenoid bones was performed. Scans were analyzed for a lateral recess, bony
      defects, arachnoid pits, and holes possibly representing Sternberg's canal. Data
      were compared with a case series of lateral sphenoid CSF leaks. RESULTS: Average
      patient age was 38.7 years (10-92 years). A sphenoid lateral recess was present
      in 35.3% (17.4% bilateral) of cases. Arachnoid pits were present on the floor of
      the middle cranial fossa in 23.4% of cases. Seven skull base defects were
      identified. Only one traveling medial to V2 resembled the description of
      Sternberg's canal. In contrast, a case series of 25 patients with lateral
      sphenoid sinus CSF leaks all had a lateral recess, defects, and arachnoid pits
      lateral to V2 (p < 0.00001). CONCLUSION: Sternberg's canal as historically
      defined is not nearly as prevalent as previously reported. Furthermore, the
      presence of arachnoid pits in all sphenoid CSF leaks and the predominant leak
      location lateral to the sites of fusion of ossification centers suggests that the
      leaks are acquired. Contributing factors may include arachnoid pits/weaknesses in
      the skull base and intracranial hypertension.

PMID- 19401044
TI  - Do single-photon emission computerized tomography findings predict severity of
      chronic rhinosinusitis: a pilot study.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is basically an inflammatory disease of
      the mucosa and periosteum of the sinuses. The possibility of local osteitis can
      cause persistent mucosal inflammation and lead to failure of treatment. Bone
      scintigraphy is the gold standard procedure for detecting the bone involvement.
      This study was designed to evaluate whether single-photon emission computerized
      tomography (SPECT) findings predict severity of chronic sinusitis and subjective
      response to medical treatment. A prospective case control study was done.
      METHODS: Twenty-four patients with CRS were involved. SPECT findings for bone
      involvement and computed tomography-based staging (limited disease, stage 1;
      extensive disease, stages 2 and 3) were compared. These data were also analyzed
      in terms of subjective response to medical treatment and prognosis. RESULTS:
      SPECT uptakes were positive in 79.2% (19/24) and negative in 20.8% (5/24) of the
      patients. SPECT was positive in 4/8 of the patients with limited disease and
      15/16 of the patients with extensive disease. In subjective assessment of medical
      treatment 5/8 of the limited disease versus 1/16 the extensive disease patients
      had good response; whereas 5/5 of SPECT(-) patients versus 1/19 of SPECT(+)
      patients had good response. CONCLUSION: Bone SPECT results were found to be
      correlated with the stage of CRS. Poorer subjective response was observed in
      patients with positive SPECT.

PMID- 19401045
TI  - Contribution of nasal biopsy to leprosy diagnosis.
AB  - BACKGROUND: The nasal mucosa plays the main role as the entry and the exit of
      leprosy bacilli and the nasal involvement may precede the skin lesions by several
      years. Nasal biopsy has been used in research but its clinical application has
      not been described. We evaluated the contribution of the nasal biopsy for the
      diagnosis of leprosy and its correlation to skin biopsy and skin smear in
      untreated patients. METHODS: We evaluated changes in nasal biopsy in 227 leprosy
      patients. Patients were clinically classified and skin and nasal biopsies and
      skin smear were performed. RESULTS: Nasal biopsy showed positivity in 100% of the
      lepromatous spectrum decreasing toward the tuberculoid (TT) pole. Patients with
      TT or indeterminate forms did not present any nasal alterations, showing that
      they are the true paucibacillary forms. Also, the nasal biopsies of two patients
      were the only exam to show positivity. The bacillary index of the nasal biopsy
      was strongly correlated to skin biopsy and slit-skin smear. Additionally, the
      agreement among the exams was good, revealing the reliability of the nasal biopsy
      in leprosy diagnosis. CONCLUSION: The present study showed a rate of 48% of
      positivity in nasal biopsy of untreated patients, correlating well with skin
      biopsy and skin smear. Thus, the method in leprosy diagnosis and clinical form
      classification has shown great reliability.

PMID- 19401046
TI  - Endoscopic endonasal repair of difficult-to-access cerebrospinal fluid leaks of
      the frontal sinus.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) leaks located within the frontal sinus can
      be difficult to repair effectively. Additional challenges arise from the need to
      simultaneously repair the leak or defect and to ensure the future patency of the
      sinus itself. METHODS: The cases of two patients who underwent surgical repair of
      CSF leaks and skull base defects located in difficult to access locations within
      their frontal sinuses were reviewed. RESULTS: Two patients with CSF leaks in the
      frontal sinus underwent surgery to repair the leaks. The leaks were in the
      superomedial and superolateral locations within the sinus. One leak (in the
      superolateral location) was secondary to iatrogenic surgical trauma during
      craniotomy. The second leak (in the superomedial location) was secondary to
      congenital encephalocele. Surgical approach to ensure adequate exposure was via
      endoscopic modified Lothrop procedure. Successful repair was undertaken via
      underlay technique. At follow-up (27 and 7 months, respectively), frontal sinuses
      remained patent without evidence of CSF leak. CONCLUSION: CSF leaks located in
      medial and lateral areas of the frontal sinus may be successfully repaired via
      endonasal approach with endoscopic modified Lothrop. Repair in this manner
      requires that attention be paid both to achieving a complete repair and to
      maintaining a patent sinus drainage pathway.

PMID- 19401047
TI  - Factors contributing to failure in endoscopic skull base defect repair.
AB  - BACKGROUND: Endoscopic repair of skull base (SB) defects is successful in over
      90% of cases. Certain factors may contribute to failure of SB repair techniques
      or need for secondary repair. METHODS: Five-year retrospective review of
      endoscopic SB defect repairs performed by a single surgeon. RESULTS: Eighty-nine
      patients undergoing 110 procedures to repair 97 SB defects were evaluated.
      Etiology of defects included surgical/iatrogenic (64%), spontaneous (17%),
      traumatic (12%), congenital (6%), and idiopathic (1%). Defects occurred in the
      sella (41%), sphenoid sinus (18%), ethmoid roof (17%), olfactory cleft (16%),
      frontal sinus/recess (6%), and middle cranial fossa (2%). Sixty-three patients
      (71%) underwent primary SB defect repair and 26 patients underwent secondary
      repair (29%). In revision cases, mean number of prior repair attempts was 1.5
      (range, 1-4). Factors potentially contributing to need for secondary SB defect
      repair included inability to localize SB defect (p =0 .008), development of new
      SB defect, prior sinus or SB surgery (p < 0.001), prior craniotomy (p < 0.001),
      prior radiation therapy (p = 0.002), and intracranial infection (p = 0.023). SB
      defects were successfully closed in 83 patients overall (93%), with success
      achieved in 97% of primary patients and 85% of secondary patients. Of failures, 3
      patients required craniotomy for defect closure, 2 patients underwent permanent
      cerebrospinal fluid (CSF) diversion, and 1 patient has persistent CSF rhinorrhea.
      CONCLUSION: Although endoscopic repair of SB defect remains largely successful,
      certain factors should alert the surgeon to the potential for failure of repair
      or need for secondary SB defect repair.

PMID- 19401048
TI  - Endoscopic anatomy of the petrous segment of the internal carotid artery.
AB  - BACKGROUND: Exposure of the petrous (C2) segment of the internal carotid artery
      (ICA; petrous carotid) is necessary to treat lesions that have spread from the
      intracranial space or adjacent sinonasal region. Recent advancements in endonasal
      endoscopic approaches to the anterior skull base raise the possibility of
      extending these approaches beyond the sinonasal cavity. In this cadaveric study,
      we evaluate the feasibility and extent of exposure of the petrous carotid artery
      via a combined endoscopic endonasal approach. METHODS: Endoscopic dissection was
      performed in four formalin-fixed cadaver heads (eight sides). An endoscopic,
      endonasal, transmaxillary approach was used to identify the cervical and petrous
      carotid artery. RESULTS: With the endoscopic endonasal, Caldwell-Luc approach, we
      could visualize the ventral petrous bone after dissecting the contents of the
      pterygopalatine fossa and infratemporal fossa. Careful dissection allowed
      exposure of the petrous carotid artery from the upper cervical carotid to the
      foramen lacerum. CONCLUSION: In this cadaveric study using an endoscopic
      endonasal approach for exposure of the petrous carotid artery, combination with
      the transmaxillary-transpterygopalatine-transinfratemporal approaches permitted
      exposure of the ventral portion of the artery. The anatomy presented will assist
      experienced endoscopic skull base surgeons in the removal of lesions involving
      the ventral skull base.

PMID- 19401049
TI  - Endoscopic ligation of the sphenopalatine artery and the maxillary artery for the
      treatment of intractable posterior epistaxis.
AB  - BACKGROUND: Intractable posterior epistaxis sometimes requires intensive
      treatment, such as surgery or embolization. Maxillary artery ligation has been
      widely used for the treatment of intractable posterior epistaxis. It is highly
      effective, but significant complications may occur, including an oroantral
      fistula and damage to the infraorbital nerve. Embolization is less invasive and
      can be performed in poor surgical candidates. However, it has more serious
      complications, such as facial nerve paralysis and hemiplegia. This investigation
      evaluates the effectiveness and complications of endoscopic ligation of the
      sphenopalatine or maxillary artery for the treatment of intractable posterior
      epistaxis. METHODS: Between April 2003 and March 2007, 46 patients were
      hospitalized for the treatment of severe posterior epistaxis in our University
      Hospital. Thirty patients were successfully treated by anterior and/or posterior
      nasal packing, and five patients were treated by electrocoagulation. Endoscopic
      ligation was performed under general anesthesia in 11 patients (6 men and 5
      women; age range, 50-80 years). RESULTS: Eight patients underwent endoscopic
      ligation of the sphenopalatine artery, and three patients underwent endoscopic
      ligation of the maxillary artery through the middle meatus and posterior antral
      wall opening. There were no complications, and the patients' postoperative
      courses were uneventful. Recurrent epistaxis occurred in one patient on oral
      anticoagulants 15 months after ligation of the sphenopalatine artery, and it was
      successfully treated by anterior nasal packing. CONCLUSION: Endoscopic ligation
      of the sphenopalatine or maxillary artery is safer than arterial embolization and
      is less invasive than transantral ligation of the maxillary artery. This
      technique appears to be a simple and highly effective surgical treatment for
      patients with intractable posterior epistaxis.

PMID- 19401050
TI  - Endoscopic transnasal transethmoid ligation of the anterior ethmoid artery.
AB  - BACKGROUND: The current otolaryngologic literature is lacking in basic science
      investigation regarding endoscopic anterior ethmoid artery (AEA) ligation as part
      of the armamentarium for epistaxis control. This investigation provides the
      anatomic rationale for endoscopic ligation of the AEA in the surgical treatment
      of epistaxis. In addition, it provides tools for identification of this vessel
      during routine endoscopic sinus surgery. METHODS: This descriptive cadaver study
      investigates the feasibility of endoscopic transnasal transethmoid dissection;
      anatomic description; and clip ligation within the periorbital space of 16 AEA
      specimens. A careful assessment for skull base penetration and disruption was
      performed. RESULTS: All 16 anterior ethmoid arteries were readily identified and
      successfully clipped. The anatomy was carefully observed and described for each
      specimen, and no inadvertent skull base penetration occurred. CONCLUSION: This
      study confirms that endoscopic ligation of the AEA is a safe and feasible
      technique for the control of epistaxis. Additionally, this anatomic knowledge is
      beneficial during routine endoscopic sinus surgery if AEA injury should occur.
      Further evaluation is necessary for clinical application of this technique in the
      treatment of epistaxis.

PMID- 19401051
TI  - Treatment results of sinonasal inverted papilloma: an 18-year study.
AB  - BACKGROUND: This article reviews our treatment results of sinonasal inverted
      papilloma (SNIP) over the past 18 years. A retrospective observational study was
      performed. METHODS: Fifty-six patients with SNIP seen between 1990 and 2008 with
      follow-up of >2 years were retrospectively analyzed. RESULTS: Forty patients
      (71%) had primary endoscopic resection and 16 patients (29%) had endoscopic
      assisted external approaches. Ten patients (18%) had small nasoethmoid residual
      disease resectable under local anesthesia in the outpatient department. Eight
      patients (14%) had recurrences requiring revision under general anesthesia, most
      of which were maxillary and frontal disease requiring additional external
      approaches. Comparing patients with and without a history of previous surgery
      (36% versus 64% of all patients), the former had a higher chance of requiring
      external approaches during the primary resection (45% versus 29%), a higher
      recurrence rate (45% versus 25%), and a higher chance of external approaches for
      revision (44% versus 22%). All the first recurrences were at the original tumor
      site. Eighty-nine percent of the first recurrences were diagnosed within the
      first 2 years postoperation. CONCLUSION: Thirty-two percent of our patients had
      recurrence after their primary resection. Recurrences in the nasoethmoid area are
      usually small and resectable endoscopically under local anesthesia in the
      outpatient department whereas those inside the maxillary and frontal sinuses are
      likely to require additional external approaches under general anesthesia. A
      minimum of 2 years of follow-up is recommended for the preliminary report on the
      treatment results of this condition. Lifelong follow-up is recommended for
      possible late recurrences and metachronous multifocal disease.

PMID- 19401052
TI  - A comparison of two sphenoidotomy approaches using a novel computerized
      tomography grading system.
AB  - BACKGROUND: Endoscopic management of sphenoid sinus disease has great potential
      for surgical complications. A variety of endoscopic surgical techniques have been
      described for entering the sphenoid sinus. The utility of these surgical
      techniques is based on the position of the superior turbinate attachment to the
      sphenoid face (Parson's ridge). We introduce a novel computerized tomography (CT)
      grading system for the attachment of the superior turbinate to the sphenoid face.
      Using this new grading system, we recommend a safer systematic approach for entry
      into the sphenoid sinus. METHODS: A grading based on the attachment of the
      superior turbinate to the sphenoid face at the level of the natural sphenoid
      ostium was developed. A total of 53 patients were enrolled. Types A, B, and C
      refer to the superior turbinate attachment at the medial, middle, or lateral
      third of the anterior sphenoid face, respectively, and type D refers to orbital
      attachment of the superior turbinate. The surgical approach used (superior
      turbinate intact [STI] or superior turbinate resection [STR]) was recorded and
      correlated to the type of superior turbinate attachment. RESULTS: The overall
      incidence of the various superior turbinate attachments were 40% (41) for type A,
      41% (42) for type B, 18% (19) for type C, and 1% (1) for type D. STR was used in
      38 sides (44%) and STI was used in 48 sides (56%). Spearman correlation study
      showed that the closer the superior turbinate attachment was to the orbit the
      more likely STR was used as the choice of entry into the sphenoid (p < 0.001).
      CONCLUSION: To perform a safe sphenoid entry it is pertinent to evaluate the
      superior turbinate attachment to the sphenoid face before making a decision on
      the method of entry.

PMID- 19401053
TI  - The utility of cadaver dissection in endoscopic sinus surgery training courses.
AB  - BACKGROUND: Understanding paranasal sinus anatomy is crucial for successful
      outcomes in endoscopic sinus surgery (ESS). This study was designed to evaluate
      subjective and objective differences in ESS cadaver dissections among
      participants of varying experience levels in association with the use of image
      guidance and computer-aided technologies in a physician training cadaver
      dissection laboratory. METHODS: Participants in a 2-day cadaver dissection course
      completed daily predissection surveys evaluating subjective comfort with ESS. Pre
      and postdissection computer tomography (CT) scans assessed completeness of
      dissection. Images were analyzed for maxillary antrostomy, frontal and sphenoid
      sinusotomy, residual ethmoid cells and partitions, and residual frontal recess
      cells. RESULTS: Fifty-one sides were dissected. Participant comfort increased
      significantly from day 1 to 2 for overall ESS (p = 0.001) and for individual
      sinuses (p < 0.001 to p = 0.047). Participants with more years in practice had
      fewer unopened ethmoid cells (p = 0.015) and frontal recess cells (p = 0.014) on
      dissection day 1. Participants with increased comfort in ethmoid dissection had
      fewer retained ethmoid partitions on day 1 (p = 0.017). Observed differences on
      dissection day 1 for unopened ethmoid and frontal recess cells and retained
      ethmoid partitions were not present on day 2. No significant differences were
      found based on use of image guidance for any parameter. CONCLUSION: Surgeons with
      increased comfort and more years in practice had more complete endoscopic cadaver
      dissections initially. Differences among participants diminished on dissection
      day 2, indicating the ability to review postdissection CT scans may improve
      surgeon comfort level and completeness of dissection.

PMID- 19401054
TI  - Repair of nasal septal perforation with "cross-stealing" technique.
AB  - BACKGROUND: The aim of this study was to reveal the efficacy of the "cross
      stealing" technique in the repair of nasal septal perforation. METHODS: In a
      prospective clinical investigation, 10 patients with the complaints of crusting,
      bleeding, whistling, nasal obstruction, and pain and in whom septal perforation
      was detected underwent surgery by endonasal approach between April 2006 and
      January 2008. During surgery, the inferior-based mucoperichondrial flap was
      prepared on one side, the superior-based mucoperichondrial flap was prepared on
      the other side of the nasal septum, and they were passed to the opposite side
      through perforation. Interpositional graft was placed between flaps and sutured.
      Patients were followed for a minimum of 5 months before the evaluation of the
      results. RESULTS: Complete closure was observed in 7 of 10 (70%) patients and
      partial closure was observed in 1 patient. In 2 patients perforation was not
      closed and its size remained unchanged. CONCLUSION: The cross-stealing technique
      is advantageous in anterior-located septal perforations in that it can be
      performed endonasally and it is physiological. Because flaps are prepared in a
      vertical direction, it can be used only in small and middle-sized perforations,
      which restricts its use.

PMID- 19401055
TI  - Minitrephination of the frontal sinus: indications and uses in today's era of
      sinus surgery.
AB  - BACKGROUND: This study reviews the role of frontal sinus minitrephination in
      today's era of endoscopic sinus surgery. Retrospective chart review was performed
      of 163 patients undergoing a total of 149 bilateral and 39 unilateral frontal
      sinus minitrephinations. METHODS: Charts were reviewed for patient demographics
      and outcomes. Details obtained from the chart included type of surgery performed,
      reason for minitrephine placement, pathology, Lund score, complications, and
      endoscopic patency. RESULTS: One hundred eighty-eight minitrephines were placed
      during 80 modified Lothrop and 108 frontal sinusotomies. Trephines were placed
      when there was difficulty finding the frontal recess, severe edema/polyps,
      obstructing frontal cells (type 3/type 4 frontoethmoidal cells and intersinus
      septum cell), and to aid the dissection and postoperative irrigation during the
      modified Lothrop. Twelve complications occurred with infection at the trephine
      site being the most common. Follow-up ranged from 2 to 122 months (average, 25.5
      months) with 92% showing endoscopic patency at last visit. CONCLUSION: Frontal
      sinus trephination is a safe useful procedure that can be extremely helpful in
      identifying the pathway to the frontal sinus. Fluorescein flushes through the
      trephine help guide the dissection in a modified Lothrop. Lastly, it may be used
      in the postoperative period to flush the sinus with saline and steroids to
      promote patency of the frontal sinus.

PMID- 19401056
TI  - Microdebrider-assisted endoscopic marsupialization for the nasolabial cyst:
      Comparisons between sublabial and transnasal approaches.
AB  - BACKGROUND: The incidence of nasolabial cysts is very low. Simple excision
      through a sublabial approach is the treatment of choice. The aim of this study
      was to evaluate the microdebrider as a tool in transnasal endoscopic
      marsupialization for nasolabial cysts and compare it with conventional
      instruments and a sublabial approach for cyst removal. METHODS: Retrospective
      chart review of 30 patients (31 cysts) with a mean age of 46.9 years received
      surgical treatments for nasolabial cysts. We performed three types of surgical
      procedures including the sublabial approach (10 cysts), conventional transnasal
      marsupialization (13 cysts), and microdebrider-assisted marsupialization (8
      cysts). RESULTS: Patients that received surgery with the sublabial approach
      experienced significant increases in operation time, blood loss, and hospitalized
      time compared with those treated with transnasal marsupialization. However, the
      number of postoperative stoma stenoses was higher for conventional transnasal
      marsupialization (two cases). No recurrences or other postoperative complications
      were found during the follow-up. CONCLUSION: The transnasal marsupialization of
      nasolabial cysts has remarkable benefits compared with sublabial cyst excision
      during operation. Microdebriders can be used safely and effectively in endoscopic
      marsupialization without stoma stenosis.

PMID- 19401057
TI  - What defines a Thai, Caucasian, or Asian?

PMID- 19401059
TI  - PET/CT and occult primary tumors.
AB  - Within the past 5 years, F-18 fluorodeoxyglucose (FDG) PET/CT has become one of
      the more frequent imaging modalities in the management of patients with cancer of
      unknown primary origin. FDG PET/CT detects more sites of metastasis than other
      modalities, and in 20% to 40% of cases it discloses the site of the primary
      tumor. Its exact role is yet to be defined because of a lack of prospective
      clinical trials comparing the performance of PET/CT with conventional anatomic
      imaging modalities. This article reviews the available literature, attempts to
      place PET/CT using F-18-labeled FDG in clinical perspective and compares the
      combined modality with conventional anatomic imaging technologies.

PMID- 19401060
TI  - Melanoma.

PMID- 19401061
TI  - Review of evidence-based support for pretreatment imaging in melanoma.
AB  - When making a new diagnosis of melanoma, clinicians often obtain imaging studies
      to rule out clinically occult distant disease. These studies range from
      inexpensive tests, such as chest radiographs, to more expensive studies, such as
      PET/CT. The impetus for ordering these studies is usually the desire to identify
      potentially resectable distant disease, avoid surgery when curative resection is
      not possible, and assuage patient anxiety by showing that no evidence of distant
      disease is present. However, some detrimental aspects to these studies are less
      apparent, including cost and potential for false-positive findings. Although
      routine use seems reasonable, the true benefit of these studies depends on the
      probability of clinically occult disease being present, likelihood that disease
      will be detected with the available technology, and impact of earlier detection
      on outcome. Contrary to current practice patterns, available evidence suggests
      that preoperative imaging studies are associated with significant costs and
      minimal benefit in most patients with melanoma. This article reviews available
      literature on the role of pretreatment imaging in patients with newly diagnosed
      cutaneous melanoma.

PMID- 19401062
TI  - Where are we with adjuvant therapy of stage III and IV melanoma in 2009?
AB  - Adjuvant therapy options for advanced melanoma in 2009 remain active observation,
      high-dose interferon, or clinical trial participation. Close observation is
      currently the only required adjuvant management, with the purpose of detecting
      the emergence of regional or metastatic disease early, when surgical management
      may still be possible. The National Comprehensive Cancer Network guidelines for
      the workup and follow-up of all stages of melanoma must be tailored to specific
      patients by the treating physician. This article explores the factors to consider
      when individualizing care within the scope of these guidelines.

PMID- 19401063
TI  - Role of sentinel lymph node biopsy in patients with thin melanoma.
AB  - Sentinel lymph node (SLN) biopsy has emerged over the past 2 decades as a
      rational approach for staging regional lymph nodes in patients with clinically
      node-negative melanoma (stage I and II disease). Large multi-institutional
      studies have confirmed that when performed by experienced surgeons, it is an
      accurate, reliable technique for identifying occult regional nodal disease, and
      that SLN status is the most important prognostic factor in patients with stage I
      and II melanoma. However, the incidence of occult regional nodal metastasis in
      patients with thin melanoma (<or= 1.0 mm; approximately 70% of patients with
      newly diagnosed melanoma) is low, and whether to perform SLN biopsy in these
      patients remains controversial. Several predictors of SLN metastasis in patients
      with thin melanoma have been suggested, but none widely accepted. This article
      reviews current literature on these predictors in patients with thin melanoma.
      Although the ability to draw conclusions was limited by the size and design of
      the available studies, the authors tentatively conclude that SLN biopsy can be
      considered for patients with melanomas 0.75 mm or larger, those with T1b
      melanomas (i.e., <or= 1.0 mm; Clark level IV/V and/or ulcerated), and those with
      thin melanomas with an increased tumor mitotic rate (especially >or= 1
      mitosis/mm2). Including younger age (e.g., <or= 40 years) in the decision also
      seems reasonable, particularly if the primary tumor is associated with a high
      tumor mitotic rate. Tumor regression does not seem to be associated with an
      increased risk for SLN metastasis. Firm conclusions on the predictive value of
      vertical growth phase, absence of tumor-infiltrating lymphocytes, or male gender
      were not possible, particularly if used as a sole criterion for offering this
      procedure. SLN biopsy should be discussed with all patients with newly diagnosed
      thin melanoma.

PMID- 19401064
TI  - Merkel cell carcinoma.

PMID- 19401065
TI  - Merkel cell carcinoma: a review of current advances.
AB  - Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy of
      neuroendocrine origin. Its incidence has tripled over the past 15 years. This
      article reviews the recent advancement in diagnosis, discoveries in pathogenesis,
      and updates in management. The acronym, AEIOU, has been proposed to aid in
      clinical identification. In addition to cytokeratin 20, newer immunohistochemical
      stains (in particular thyroid transcription factor-1 and neurofilament protein)
      have proven to be essential in pathologic diagnosis. Although immune suppression
      and ultraviolet radiation have long been associated with the MCC oncogenesis,
      recent studies also show involvement of a new polyomavirus and bcl-2. Several
      tumor classifications have been published in the literature, with the 4-tiered
      system from Memorial Sloan-Kettering Cancer Center the most widely used. A
      similar classification with additional distinctions among nodal disease is being
      constructed. A multidisciplinary treatment algorithm is recommended for MCC.
      Surgical excision with adjuvant radiotherapy (RT) is indicated for localized
      tumors. RT is favored over complete lymph node dissection and chemotherapy for
      regional lymph node involvement. For distant metastasis, management should be
      individualized with a combination of palliative surgery, RT, and chemotherapy.

PMID- 19401067
TI  - Child Dental Health Survey 2007: a snapshot of the oral health status of primary
      school-aged children in NSW.
AB  - OBJECTIVES: The Child Dental Health Survey 2007 was commissioned to establish the
      oral health status of school children in NSW aged 5-12 years, to provide reliable
      regional oral health statistics and contribute to national population-based data
      collections. METHODS: A total of 7975 children were clinically examined at 107
      public, catholic and independent schools across NSW. RESULTS: Key findings from
      the survey include: mean dmft for 5-6-year-olds of 1.53; mean DMFT for 11-12-year
      olds of 0.74; 61.2% of 5-6-year-olds and 65.4% of 11-12-year-olds have never
      experienced decay in their primary and permanent teeth, respectively. These
      figures compare favourably to national benchmarks set in 2001. CONCLUSIONS: Data
      from the survey will be used as a baseline to measure the success of early
      intervention and prevention programs, for international comparisons, to provide
      solid evidence to support population oral health planning and for ongoing
      surveillance of populations of interest.

PMID- 19401066
TI  - Randomised controlled trial to determine the clinical effectiveness and cost
      effectiveness of selective serotonin reuptake inhibitors plus supportive care,
      versus supportive care alone, for mild to moderate depression with somatic
      symptoms in primary care: the THREAD (THREshold for AntiDepressant response)
      study.
AB  - OBJECTIVES: To determine (1) the effectiveness and cost-effectiveness of
      selective serotonin reuptake inhibitor (SSRI) treatment plus supportive care,
      versus supportive care alone, for mild to moderate depression in patients with
      somatic symptoms in primary care; and (2) the impact of the initial severity of
      depression on effectiveness and relative costs. To investigate the impact of
      demographic and social variables. DESIGN: The study was a parallel group, open
      label, pragmatic randomised controlled trial. SETTING: The study took place in a
      UK primary care setting. Patients were referred by 177 GPs from 115 practices
      around three academic centres. PARTICIPANTS: Patients diagnosed with new episodes
      of depression and potentially in need of treatment. In total, 602 patients were
      referred to the study team, of whom 220 were randomised. INTERVENTIONS: GPs were
      asked to provide supportive care to all participants in follow-up consultations
      2, 4, 8 and 12 weeks after the baseline assessment, to prescribe an SSRI of their
      choice to patients in the SSRI plus supportive care arm and to continue treatment
      for at least 4 months after recovery. They could switch antidepressants during
      treatment if necessary. They were asked to refrain from prescribing an
      antidepressant to those in the supportive care alone arm during the first 12
      weeks but could prescribe to these patients if treatment became necessary. MAIN
      OUTCOME MEASURES: The primary outcome measure was Hamilton Depression Rating
      Scale (HDRS) score at 12-week follow-up. Secondary outcome measures were scores
      on HDRS at 26-week follow-up, Beck Depression Inventory, Medical Outcomes Study
      Short Form-36 (SF-36), Medical Interview Satisfaction Scale (MISS), modified
      Client Service Receipt Inventory and medical record data. RESULTS: SSRIs were
      received by 87% of patients in the SSRI plus supportive care arm and 20% in the
      supportive care alone arm. Longitudinal analyses demonstrated statistically
      significant differences in favour of the SSRI plus supportive care arm in terms
      of lower HDRS scores and higher scores on the SF-36 and MISS. Significant mean
      differences in HDRS score adjusted for baseline were found at both follow-up
      points when analysed separately but were relatively small. The numbers needed to
      treat for remission (to HDRS > 8) were 6 [95% confidence interval (CI) 4 to 26)]
      at 12 weeks and 6 (95% CI 3 to 31) at 26 weeks, and for significant improvement
      (HDRS reduction > or = 50%) were 7 (95% CI 4 to 83) and 5 (95% CI 3 to 13)
      respectively. Incremental cost-effectiveness ratios and cost-effectiveness planes
      suggested that adding an SSRI to supportive care was probably cost-effective. The
      cost-effectiveness acceptability curve for utility suggested that adding an SSRI
      to supportive care was cost-effective at the values of 20,000 pounds-30,000
      pounds per quality-adjusted life-year. A poorer outcome on the HDRS was
      significantly related to greater severity at baseline, a higher physical symptom
      score and being unemployed. CONCLUSIONS: Treatment with an SSRI plus supportive
      care is more effective than supportive care alone for patients with mild to
      moderate depression, at least for those with symptoms persisting for 8 weeks and
      an HRDS score of > or = 12. The additional benefit is relatively small, and may
      be at least in part a placebo effect, but is probably cost-effective at the level
      used by the National Institute for Health and Clinical Excellence to make
      judgements about recommending treatments within the National Health Service.
      However, further research is required.

PMID- 19401068
TI  - The oral health of adults in NSW, 2004-06.
AB  - OBJECTIVES: The 2004-06 National Survey of Adult Oral Health was Australia's
      second oral examination survey of a nationally representative sample of adults.
      The aim of this paper is to provide a brief overview of oral health in the NSW
      adult population from the findings of the survey. METHODS: A three-stage,
      stratified, clustered sampling design was used to select NSW residents aged 15
      years and over. Self-reported information about oral health was obtained through
      telephone interviews. People with natural teeth were offered clinical
      examinations. RESULTS: 3630 people were interviewed and 1099 underwent a clinical
      examination. Only 5.5% of the study population were edentulous (all natural teeth
      missing) compared with the national estimate of 6.4%. The Decayed, Missing,
      Filled Teeth (DMFT) caries severity index was 12.8, equal to that of the
      Australian population; prevalence of untreated decay was 27.1%, which was not
      significantly different to the national estimate of 25.5%. Some 60.3% of the NSW
      survey sample had visited a dentist within the last 12 months (nationally 59.4%)
      and 56.8% visited for a check-up (56.2% nationally). Oral health, use of dental
      services and perceptions of need varied significantly by geographic location,
      private insurance patronage and eligibility for public dental care. CONCLUSIONS:
      The oral health of the NSW adult population and patterns of dental care are
      similar to that estimated nationally. The prevalence and severity of dental
      diseases and oral health behaviours are influenced by social and geographic
      factors.

PMID- 19401069
TI  - Comparison of the dental health of adults and children living in NSW with their
      counterparts in the US and UK.
AB  - This paper aims to place the findings of the NSW Adult and Child Dental Health
      Surveys in an international context. The comparator countries are the US and the
      UK, both of which have well-documented epidemiological dental health data. The US
      has a mainly private system of dental care, similar to NSW, whereas the UK has
      primarily a government-funded dental care program. The adult data collected in
      the last 20 years in all three locations indicates greatly improved oral health
      with a decline in the proportions of people with no natural teeth. The majority
      of children have few dental problems but inequality remains with some children in
      lower socioeconomic groups still having high levels of dental ill health, which
      contributes to a lower quality of life. Improving population levels of oral
      health in all three countries will require collective decision-making by
      stakeholders and politicians to finance plans for action and manage change to
      help those individuals for whom dental disease is still a major problem.

PMID- 19401070
TI  - Rural oral health workforce issues in NSW and the Charles Sturt University
      Dentistry Program.
AB  - Adequate numbers of dental, medical and allied health professionals in rural and
      regional areas of NSW are vital for the health of these populations and
      supporting local community structures and economies. Well-documented shortages of
      health professionals are a major social and political issue in rural and regional
      communities and this workforce shortfall is recognised by both the NSW Government
      State Plan and the State Health Plan. This paper outlines rural and regional
      dental workforce shortages in NSW and describes current rural oral health
      workforce initiatives, including the new Charles Sturt University Dentistry
      Program.

PMID- 19401072
TI  - [Primary myringoplasties. Results after a 2 year follow-up period].
AB  - INTRODUCTION AND GOALS: The goals of myringoplasty are closure of the perforation
      in the tympanic membrane and improvement in hearing levels, with varying results
      in the published literature. Our aim was to determine the results of this
      procedure at our centre and compare them with the literature. METHODS:
      Retrospective analysis of 217 primary myringoplasties carried out in the
      Otorhinolaryngology Department of the Ramon y Cajal University Hospital between
      1998 and 2003, describing the characteristics of the perforations, surgical
      technique and post-operative results (perforation closure and hearing
      improvement). RESULTS: The majority were adults with perforations secondary to
      recurrent middle ear infections (91%). Most were less than subtotal (64%) and did
      not involve the tympanic annulus (79%). Grafts were inserted using lateral (45%),
      mixed (29%) and medial (26%) techniques, using retroauricular (66%) and endaural
      (34%) approaches. Temporal muscle fascia was the graft most frequently used
      (87%). Perforation closure was achieved in between 78% and 91% of cases
      throughout the 24-month follow-up period, with an overall closure value of 78%
      after 2 years of follow-up. Hearing improvement, established as an air bone gap
      difference of less than 20 dB, was seen in approximately 56% of cases.
      CONCLUSIONS: At our centre, myringoplasty achieves anatomical (78%) and
      functional (56%) success comparable to the results described in the literature.
      We consider medium-term follow-up to be of the utmost importance because of
      reperforation phenomena, which may occur as much as 2 years or more after
      surgery.

PMID- 19401073
TI  - [Tympanostomy tube placement in children with secretory otitis media: analysis of
      effects and complications].
AB  - INTRODUCTION AND OBJECTIVES: Tympanostomy tube emplacement is a common surgical
      procedure in paediatric otolaryngological surgery. This surgery has complications
      that sometimes depend on the disease and at other times on the treatment. The
      objective of this study is to know the results obtained with tympanostomy tube
      emplacement and its complications. MATERIAL AND METHODS: Retrospective study of
      all the children operated on for tympanostomy tube emplacement over a period of
      18 months and with follow-up for at least seven years; this amounted to 143 ears
      operated on for the first time. The study variables were age, gender, initial
      appearance of the ear, inner ear contents, type of grommet inserted, duration of
      grommet and the lack of any hospital monitoring needed after extrusion. RESULTS:
      One complication or another arose in 46% of the ears. The Donaldson type of
      grommet with a diameter of 1.27 mm is the one that produced most complications.
      There were more complications in ears that were worse in the otoscopic
      examination regardless of the grommet inserted. CONCLUSIONS: The high prevalence
      of complications and after-effects after grommet emplacement needs long-term
      follow-up in patients. The results obtained suggest the use of grommets with a
      smaller internal diameter.

PMID- 19401074
TI  - [Study of the relationship of stapedial reflex thresholds induced during cochlear
      implant surgery and the highest hearing comfort of paediatric patients].
AB  - INTRODUCTION AND GOALS: We have studied the relationship between the minimum
      stapedial reflex thresholds induced by means of the intra-operative stimulation
      of the cochlear implant and the post-operative thresholds of highest auditory
      comfort level. METHODS: We have assessed the maximum auditory comfort at the end
      of the first and second quarters following activation of the cochlear implant, by
      which time the strategy for codification of the stimuli and the programming map
      are considered to be already stable. The study was carried out at our cochlear
      implants unit. All the patients in the study had bilateral sensorineural deafness
      of varying aetiology and, following our standardized battery of diagnostic tests,
      were considered to be good candidates for cochlear implant. All aspects of the
      surgical technique were kept the same in order to be able to compare the results
      better. All members of the study were fitted with at least one Nucleus Freedom
      implant with Contour Advance Electrode. RESULTS: This study has been carried out
      on 24 cochlear implants placed in 22 patients younger than 14 years old.
      CONCLUSIONS: After assessing our experience, we can conclude that, in the Nucleus
      Freedom with Contour Advance Electrode cochlear implant, there is a positive
      statistical relationship between the levels of acoustic reflex induction obtained
      at the peri-operative stage and the levels of maximum auditory comfort, as
      determined by behavioural observation techniques for each of the different
      electrodes, in children up to 14 years old.

PMID- 19401075
TI  - [Intratympanic dexamethasone as therapeutic option in sudden sensorineural
      hearing loss].
AB  - INTRODUCTION AND OBJECTIVES: The administration of systemic corticosteroids has
      demonstrated effectiveness on the treatment of idiopathic sudden sensorineural
      hearing loss. However, its systemic toxicity and subsequent difficulty for its
      justification in some patients have led to it being applied intratympanically.
      The main aim of this study is to determine the effectiveness of intratympanic
      dexamethasone in these patients. In addition we evaluate the relationship between
      the prognosis of this condition and the magnitude of initial hearing loss, the
      presence of vertigo or delay in the beginning of therapy. METHODS: We performed a
      retrospective case study of 18 patients. All of them were treated with
      intratympanic dexamethasone (4 mg/ml), administered weekly for 3 weeks. The
      follow-up was 1 month at least. The therapeutic success was arbitrarily defined
      to be a mean improvement of 25 dB or greater. RESULTS: 72.2% of the population
      recovered hearing successfully. The mean auditory threshold prior to treatment
      was 91+/-25 dB versus 51+/-35 dB after the end of it (p<0.0005). In addition, we
      observed that the initial severity of the hearing loss, the presence of vertigo
      and the delay in starting therapy cannot be considered as indicators of poor
      auditory prognosis. CONCLUSIONS: Intratympanic dexamethasone appears to be an
      effective therapeutic option for patients with sudden onset sensorineural hearing
      loss who, for whatever reason, cannot be treated with systemic steroids.
      Nonetheless, randomized controlled trials should be instituted to improve levels
      of scientific evidence.

PMID- 19401076
TI  - [Clinical implications of iatrogenic lesion in the chorda tympani nerve during
      otosclerosis surgery].
AB  - INTRODUCTION: Damage to the chorda tympani nerve is frequent during otologic
      surgery. This article studies the clinical outcomes of the nerve's section versus
      its conservation in otosclerosis surgery. MATERIAL AND METHOD: Retrospective
      observational study using our department's otosclerosis database and a validated
      questionnaire on symptoms associated with the chorda tympani nerve. The sample
      was divided into two groups: section and conservation (patients whose nerve was
      anatomically conserved). We studied the presence and duration of symptoms, the
      surgical technique and the audiometric results. RESULTS: 78 patients (88 ears):
      section group (18 ears; 20%) and conservation group (70 ears; 80%). Overall,
      gustatory symptoms appear in 35% (39% section group; 34% conservation group).
      Differences between groups are not statistically significant in relation to
      presence and duration of symptoms, surgical technique or audiometric results.
      Only 1 patient in each group reports long-term symptoms. Our results suggest
      there are no major clinical differences following section versus conservation of
      the chorda tympani nerve. A wide range of factors such as age, presence of
      previous middle ear pathology, cross innervation and gastronomic culture may play
      a role in the appearance of symptoms. CONCLUSIONS: Symptoms appearing after
      iatrogenic damage to the chorda tympani nerve have, in general, little clinical
      relevance, especially in the long term, regardless of whether the nerve is
      dissected or manipulated to various degrees.

PMID- 19401077
TI  - [Validation of the Spanish parent satisfaction questionnaire with neonatal
      hearing screening programs].
AB  - INTRODUCTION: Although measuring parent satisfaction has been recommended as one
      of the important outcome measures in assessing the effectiveness of neonatal
      hearing screening programs, there are few published studies investigating this
      issue. OBJECTIVES: To validate the Spanish version of the Parent Satisfaction
      Questionnaire with Neonatal Hearing Screening Program (PSQ-NHSP). METHODS: 112
      parents whose children had received hearing screening participated in this study.
      RESULTS: High levels of satisfaction were reported with more than 90% of parents
      satisfied with all aspects of the program. The psychometric properties of the
      Spanish version of the PSQ-NHSP were analyzed and demonstrated good internal
      consistency (alpha=0.75). Construct validity was indicated by a significant
      positive relationship between overall satisfaction and the three specific
      dimensions in the questionnaire. DISCUSSION: The development of a valid and
      reliable parent satisfaction questionnaire is important for improving hearing
      screening programs.

PMID- 19401078
TI  - [Epidemiology and risk factors for microtia in Colombia].
AB  - INTRODUCTION AND OBJECTIVES: Microtia is a major malformation of the auricle,
      comprising a clinical spectrum ranging from a slight reduction in the size of the
      auricle or one of its parts to the complete absence of the pinna (anotia). Its
      prevalence varies according to the region of the world it is evaluated in. We
      analyzed a range of maternal, neonatal, and familial variables in a case group
      and a control group, and compared them with the existing literature. METHODS: We
      collected information from the Latin-American Collaborative Study on Congenital
      Malformations (ECLAMC) gathered between 2001 and 2006, where we found 27 cases of
      isolated microtia; we also collected information from 103 control subjects. Data
      were analyzed using Student's t and odds ratio (OR). RESULTS: Microtia
      distribution was 3 (11.1%) patients with grade I microtia, 19 (70.4%) with grade
      II microtia, 2 (7.4%) with grade III microtia. We found no patients with anotia.
      Regarding laterality, the right side was involved more often. Male-to-female
      ratio was 1.7:1. Birthweight pound 2,500 g produces an OR of 3.25 (95% CI, 1.11
      9.58) for the development of microtia. CONCLUSIONS: Microtia may be directly or
      indirectly associated with the early onset of labour. Future studies should
      include long-term follow up of the patients in order to detect possible anomalies
      of the oculo-auriculo-vertebral spectrum. It is also important to take
      anthropometric measurements to increase the likelihood of detecting cases of
      grade I microtia and mid-face hypoplasia, and to define with greater accuracy
      whether isolated microtia is the mildest form of the oculo-auriculo-vertebral
      syndrome.

PMID- 19401079
TI  - [Tumoral pathology of salivary glands. Our experience].
AB  - INTRODUCTION AND OBJECTIVES: We report a descriptive epidemiologic study of 63
      patients with major and minor salivary gland tumours diagnosed at our centre over
      the last ten years. METHODS: The data collected from all patients included
      gender, age, location, histopathology, diagnostic procedures, treatment and
      follow-up. RESULTS: Among the 38 males and 25 females, we found 39 with benign
      tumours and 24 with malignant tumours. Most of these tumours (42; 67%) arose in
      the parotid gland, 12 (19%) in the submaxillary gland, 7 (11%) in the palate and
      2 (3%) in external auditory canal. The mean age was 54 years for benign tumours
      and 80 years for malignant ones. The most common benign tumours found were
      pleomorphic adenomas (67%) whereas epidermoid carcinoma (54%) followed by
      lymphomas (25%) were the most frequent among malignant tumours. CONCLUSIONS: We
      have found two main differences with previously reported studies: the elevated
      mean age of patients with malignant tumours and, probably as a result of this
      advanced age, the high incidence of squamous cell carcinoma due to metastatic
      dissemination of skin cancers.

PMID- 19401080
TI  - [Surgical options for hearing loss in patients with osteogenesis imperfecta].
AB  - The aim of the study is to present the severe, extensive lesions in the temporal
      bone appearing in the mildest forms of osteogenesis imperfecta, correlate these
      with audiometric results and discuss the possible surgical treatments available.
      We present three patients suffering hearing loss due to osteogenesis imperfecta
      type 1 to various functional degrees. All patients underwent an audiological,
      medical and radiological evaluation and were then treated with different surgical
      procedures. The patients presented mild, severe and profound mixed hearing losses
      and the radiological images showed extensive areas of demineralization affecting
      the ossicular chain and removal of protection for the vital structures inside the
      temporal bone. Also, the cochlea showed otic capsule demineralization,
      dehiscence, distortions and even destructions. The various surgical treatments,
      indicated under current international criteria, obtained limited functional
      results. This study reviews the need to evaluate the current surgical criteria
      for this specific condition.

PMID- 19401081
TI  - [An update on the treatment of vestibular schwannoma].
AB  - The increase in the diagnosis of ever smaller vestibular schwannomas (VS), the
      fact that many tumours can be observed with serial MRI, and the development of
      radiosurgery as an alternative to microsurgery have led the neurotologic surgeon
      to a new global approach to patients with VS. On the other hand, the spread of
      internet-based information sources, often with biased or incomplete information,
      makes counselling patients with VS a challenging task. This study provides an
      overview of the natural history of these tumours and the main therapeutic
      options: observation, surgery and radiosurgery, with comments on their
      indications, advantages and disadvantages. Due to the completely different
      approach and peculiar features of bilateral VS in patients with type II
      neurofibromatosis, these are excluded.

PMID- 19401082
TI  - [Small round cell desmoplastic tumour. Atypical morphology in the sub-maxillary
      gland].
AB  - Desmoplastic small round cell tumour (DSRCT) is a rare disease usually affecting
      young males. There are no other articles with a sub-maxillary location. The
      tumour consists of nests and masses of undifferentiated small round cells
      embedded in a desmoplastic stroma. The co-expression of epithelial, muscular and
      neuronal antigens distinguishes this entity from other small round cell tumours.
      The t(11;22)(p13;q12) translocation is a recurrent characteristic of this type of
      tumour. We report a case of desmoplastic small round cell tumour of the sub
      maxillary gland, with an evolution of 8 months, affecting a 36 year old male. He
      suffered chronic lymphatic leukaemia five years ago and needed a bone marrow
      transplant. There was a 4x3 cm tumour. There were no signs of malignancy on the
      CT scan. A right sub-maxillectomy was performed. The pathology analysis gave a
      diagnosis of DSRCT. Post-surgical radiotherapy was given. The definitive
      diagnosis was reached using immunohistochemical techniques, such as
      polyphenotypical differentiation (epithelial, mesenchymal and neural), and by
      demonstration of translocation (11;22)(p13;q12). Sub-maxillary location is very
      rare.

PMID- 19401083
TI  - [First-bite syndrome].
AB  - First-bite syndrome consists of the appearance of pain in the parotid at the
      beginning of mastication, due to damage to the cervical sympathetic chain or the
      sympathetic plexus innervating the parotid gland. Clinical presentation in a
      patient who has undergone surgery of the parapharyngeal space suggests the
      diagnosis. We report here the case of a patient who presented first-bite syndrome
      after being operated on for a cervical sympathetic chain schwannoma.

PMID- 19401084
TI  - [Ossifying fibroma of the mastoid area].
AB  - Ossifying fibromas are rare fibro-osseous lesions occurring in maxilla or
      mandible. However, there have been reports of the lesion developing in nasal
      bones, paranasal sinus or the eye socket. We describe here a case of ossifying
      fibroma in the temporal bone with a review of the current literature.

PMID- 19401086
TI  - [Research in nursing].

PMID- 19401085
TI  - [Odontogenic keratocist].

PMID- 19401087
TI  - [Evaluation of pain during posture change in patients with invasive mechanical
      ventilation].
AB  - INTRODUCTION: The evaluation of pain poses special difficulties in critical
      patients who have altered verbal communication. OBJECTIVES: Compare the behaviour
      responses to pain, measured with the Critical-Care Pain Observation Tool (CPOT)
      scale and the physiological responses before, during and after the posture change
      procedure in patients with invasive mechanical ventilation. Analyze if there are
      any differences in the COPT score between medical and surgical patients and
      between the conscious and unconscious patients in the posture change procedure.
      Describe the analgesia/sedation administered to the patients 1 hour before and
      during the posture change procedure. MATERIAL AND METHODS: This descriptive,
      prospective study evaluated pain during turning/postural changes in 201
      observations performed in 56 patients. Data collection was made 1 minute before,
      during, and 10 minutes after the procedure using the COPT scale that includes
      four indicators: facial expression, body movements, muscle tension and adaptation
      to the ventilator. In the same way, the physiological variables were recorded:
      mean arterial pressure, heart rate, respiratory rate and arterial oxygen
      saturation. RESULTS: Total mean score of the CPOT scale before the procedure of
      turning was 0.30, during it 2.06 and after the procedure 0.15 with statistically
      significant differences. Facial expression was the indicator that increased the
      greatest in relationship with the baseline condition, since it occurred in 55% of
      the observations body movements increased in more than 40%; adaptation to the
      ventilator, occurred in 33% and muscular tension had an increase of 22% of the
      observations. There were also slight variations in the physiological variables
      during the postural change regarding baseline with statistically significant
      differences. Total mean score of the CPOT scale during turning of the surgical
      patients was higher than medical patients (p = 0.018). Patients received
      analgesia/sedation one hour prior to the procedure in 99.5% of the observation
      and additional analgesia for the postural change was only administered in 13% of
      the observations. CONCLUSIONS: Observation of the patient's behavior during
      posture change and the physiological changes produced allows the professionals to
      objectify the pain in the critical patients who can verbal communication
      problems.

PMID- 19401088
TI  - [Endonasal tubes as cause of pressure ulcers in the critical patient].
AB  - INTRODUCTION: One of the risks of using endonasal tubes (ET) is the appearance of
      pressure ulcers (PU). OBJECTIVE: To ascertain the proportion of patients with
      nasal PU, study the risk factors of appearance, and find predictive variables.
      MATERIAL AND METHODS: A six-month prospective, observational study of intensive
      care unit patients with ET. VARIABLES: Variable response: "the appearance of pu
      as a result of the use of ET". Explanatory variables: age, duration of stay,
      length of time with ET, gender, sedation, norepinephrine perfusion, mechanical
      ventilation, anemia, nutritional state. ANALYSIS: multivariate statistical
      techniques (multiple logistical regression). Statistics program g-stat 2.0.
      Significance level p < 0.05. RESULTS: Sample of 48 patients. Proportion of
      patients with PU: 29.2%. Those patients with PU had similar ages, duration of
      stay and longer length of time with ET. Results of the Logistic Regression model:
      only the variable "time with ET" was statistically significant (p = 0.03; odds
      ratio: 1.047). CONCLUSIONS: The length of time the patient is using an ET
      influences the appearance of nasal PU (risk increases 1.047 for each day with
      ET). None of the variables dealt with could be used as a predictive factor in the
      appearance of PU.

PMID- 19401089
TI  - [Education as a key piece in the prevention and good course of pressure ulcers].
AB  - OBJECTIVE: To evaluate if an education program for the nursing staff helps to
      reduce the incidence of pressure ulcers and prevent their poor evolution.
      MATERIAL AND METHODS: A prospective and observational study where the prevention
      and educational methods have been used to prevent and treat pressure ulcers. All
      patients admitted to Intensive Care Unit during one year were included (six
      months of basal period and six months of post-training period). The following
      variables were analyzed: incidence of Pressure Ulcers, risk score according to
      EMINA, ulcer grade and location. RESULTS: A total of 134 ulcers were identified
      in the 69 patients (14.37%) with pressure ulcers included in the basal period.
      Forty-four patients (7.88%) of the patients in the post-training period developed
      77 pressure ulcers. The significance level was p < 0.01, OR: 0.40 (95% CI: 0.26
      0.62). Fifteen of the 211 pressure ulcers evolved to grade III-IV p > 0.20.
      CONCLUSIONS: Conducting a training program in the application of standardized
      prevention methods for the nursing staff reduces the incidence of pressure
      ulcers.

PMID- 19401090
TI  - [Evaluation of the effect of a cleaning/disinfection intervention on the rate of
      multiresistant microorganism infections in the Intensive Care Unit].
AB  - AIM: Evaluate the effect of an intervention on the rate of nosocomial infections
      (NI) produced by multiresistant microorganisms in the Intensive Care Units.
      MATERIAL AND METHODS: A study was conducted before and after an intervention in
      two ICUs to control an outbreak of multiresistant Acinetobacter baumanii (MRAB).
      During the outbreak (from 22-12-06 to 12-2-07) the wards were closed and both the
      wards and the equipment of both ICUs were cleaned and disinfected. A
      microbiological sampling was also made. The nosocomial infection rate density of
      the multiresistant microorganisms was compared between hospitalized patients:
      preintervention (1-3-2006 to 15-12-2006) and postintervention (1-3-2007 to 15-12
      2007). To certify if there were any statistically significant differences between
      them, a rate ratio (RT) was calculated with a 95% confidence interval. The level
      of statistical significance was established at p < 0.05. We stratified per unit,
      per type of microorganism and location of the infection. RESULTS: The global NI
      incidence rate for multiresistant microorganisms significantly declined after the
      interventions in both units (RT: 1.83, 95% CI: 1.34-2.50), p < 0.005. A
      significant decrease was also observed on the NI incidence rate for the following
      microorganisms: P. aeruginosa (RT: 2.36, 95% CI: 1.41-3.96), Enterobacter BLEE
      (RT: 2.31, 95% CI: 1.11-4.82) and S. maltophilia (RT: 2.77, 95% CI: 1.10-6.99).
      In regards to the infection location, a significant decrease in respiratory
      infection rates was observed (RT: 1.96, 95% CI: 1.29-2.99). CONCLUSION: The
      intervention conducted to control the MRAB outbreak was effective in reducing the
      NI incidence of multiresistant microorganisms.

PMID- 19401091
TI  - [Innovation in hospital pharmacy].

PMID- 19401092
TI  - [Factors associated with adherence in HIV patients].
AB  - OBJECTIVE: To establish the relationship between the adherence to ARVT and the
      clinical situation and detect those factors which relate to the lack of
      adherence. METHOD: Observational study on HIV patients who had attended the
      Pharmacy Service in Navarra Hospital between February and May 2005. The SMAQ
      questionnaire and pharmacy dispensing records were used to assess adherence to
      treatment. Socio-demographic variables and other factors which could influence
      adherence were recorded. Statistical analysis was carried out using the SPSS
      programme, version 14.0. RESULTS: No concordance was noted between the two
      measurements of adherence, although there was an association between the viral
      load and compliance, irrespective of the method used. The questionnaire recorded
      a higher percentage of non-adhering female patients, substance users and
      psychiatric patients. Non-adhering patients indicated more frequently factors
      which made taking the medication difficult. The multivariate analysis showed that
      the lack of a suitable social-familial environment negatively influenced the
      adherence level, according to the SMAQ questionnaire, and that the high number of
      tablets per dose was related to the lack of adherence according to the pharmacy
      dispensing records. CONCLUSIONS: Patients who adhere to ARVT have a lesser risk
      of virological failure. An unsuitable social-familial environment and the
      complexity of treatment are associated with a lack of adherence. The method of
      using dispensing records should be combined with a patient interview to define
      the factors which reduce adherence and to propose intervention strategies.

PMID- 19401093
TI  - [Negative results related to drugs required in hospitalisation].
AB  - OBJECTIVE: To assess the prevalence of negative clinical outcomes associated with
      medication as a cause of hospital admission and to determine their
      characteristics (types, categories, avoidability, severity and the drug groups
      involved.) To determine possible risk factors related to the appearance of this
      problem. METHOD: An observational study carried out over a three month period in
      a department of the university hospital, 163 patients were selected at random.
      The information obtained from the patient interview, the revision of clinical
      records and clinical sessions were used to then identify negative clinical
      outcomes using the Dader method. RESULTS: In 27 cases (16.6 %; 95 % confidence
      interval [CI], 1.6 to 23.0), negative clinical outcomes associated with
      medication were considered to be the main cause of hospital admission. The most
      frequent negative clinical outcomes associated with medication were untreated
      health problems, non-quantitative ineffectiveness and quantitative safety
      problems respectively. The overall prevalence of preventable admissions due to
      negative clinical outcomes associated with medication was 88.9 %; (95 % CI, 71.9
      to 96.1 %.) With regards to severity, 74.1 % (95 % CI, 55.3 to 86.1 %) of the
      total admissions were moderate. The most common drugs implicated in hospital
      admissions were: antibacterial for systemic use, cardiovascular and non steroidal
      anti-inflammatory agents. Apart from age, no other factors were found for
      hospital admissions due to negative results associated with medication.
      CONCLUSIONS: Negative clinical outcomes associated with medication as cause of
      hospital admission are a prevalent problem and most of them are avoidable with
      pharmacotherapeutic follow-up.

PMID- 19401094
TI  - [Comparison of two formulae for the calculation of glomerular filtration in the
      dosage of zoledronic acid].
AB  - OBJECTIVE: To validate the use of a formula that does not require the patient's
      weight (Levey formula) for calculating creatinine clearance in the adjustment of
      the dosage of zoledronic acid. METHOD: Prospective observational study in which
      zoledronic acid prescriptions in the Oncology and Haematology departments were
      recorded over the course of 8 months. The adjustment of the dose of zoledronic
      acid was carried out in accordance with creatinine clearance obtained using two
      different equations; the Cockcroft-Gault equation which is based on medical
      records, and the Levey formula which does not require the patient's weight for
      the calculation. The results of zoledronic acid dosage from both equations were
      compared using the SPSS statistics programme, via the comparison of the two
      measurements using the t Student-Fisher (T-test.) RESULTS: The T-Test provided a
      t-test value of t = 3,366, with 112 degrees of freedom and a degree of bilateral
      importance of p = 0.001. The difference between both measurements was d = 0.051
      +/- 0.162) and the confidence interval was 95 %, 0.082 to 0.021. From the data
      obtained in the T-Test, the degree of bilateral importance (p = 0.001 < 0.05)
      indicated that the results of the test were statistically significant.
      CONCLUSIONS: The difference between the dosages obtained when comparing both
      methods of glomerular filtration is statistically significant, although not
      clinically relevant, therefore the MDRD-4 formula (Levey) could be used if the
      patient's weight is not available.

PMID- 19401095
TI  - [The influence of alternative medicine in highly active antiretroviral
      treatment].
AB  - OBJECTIVE: Over the last few years, there has been a notable increase in the use
      of alternative medicine by the general population. The aim of this study is two
      fold. Firstly we will analyse the incidence of the use of medicinal plants in
      patients with HIV undergoing Highly Active Anti-Retroviral Therapy (HAART).
      Secondly, with the help of existing bibliographic information, we want to study
      the existence of possible interactions. MATERIAL AND METHODS: We carried out a
      prospective study with a targeted interview (October to December 2007) on
      consenting patients with HIV undergoing HAART treatment. RESULTS: Of the 193
      patients that agreed to take part in the survey, 16.6 % confirmed they used
      alternative medicinal therapies. In 46 % of the cases there was a potential
      interaction with the effectiveness of HAART. 46 % of the potential interactions
      were in the case of the patients who used grapefruit as an alternative medicine,
      21 % in the case of patients using thistle and Echinacea respectively, 4 % for
      those using omega-3, Chinese herbs and ginseng. CONCLUSION: There is a
      significant use of natural products by these groups of patients, of which a
      significant percentage interact with HAART. A better understanding of the
      possible interactions with HAART and improved information offered to patients
      with HIV is needed.

PMID- 19401096
TI  - [Optimisation of the prescription of medication for patients undergoing elective
      surgery].
AB  - OBJECTIVE: To draw up a document in which patients can note down their
      residential treatment and determine its usefulness. The level of compliance and
      assessment of the document can be quantified by the healthcare personnel. METHOD:
      Initially the medical prescription process was analysed in the preoperative
      stage. Its usefulness was later evaluated, analysing the percentage of patients
      who could benefit from it, through a questionnaire for the healthcare personnel.
      RESULTS: A residential medication document was drawn up and included in the
      documentation process at the preoperative stage. From a sample of 350 patients,
      76.0 % took medication at home and 81.2 % of those used the document. The health
      personnel rated its usefulness as 4.51 and the safety of it at 4.38 in a scale of
      1 to 5. The time saved was valued at 4.37; 4 being a saving of between 0 and 5
      minutes, and 5 being a saving of between 5 and 10 minutes. DISCUSSION: The home
      medication document could overcome the problem of knowing exactly the home
      medication itself, and this could be the first step in therapeutic conciliation.
      According to the assessment by the healthcare personnel, it improves the
      usefulness and the efficiency of the process. According to our data, the time
      saved by the medical staff and nursing personnel fluctuates between 93-310 and
      122-339 hours per year, respectively. Computerised, up-to-date clinical records
      accessed by both primary and specialised care, could further optimise the
      prescription process of medication in the perioperative stages.

PMID- 19401097
TI  - [Adjusting the dosage of medication in institutionalised elderly patients with
      renal failure].
AB  - OBJECTIVE: To design a programme for pharmaceutical care for the elderly with
      renal failure in three nursing homes in the region of Valencia. METHOD: A nine
      month long, prospective study into pharmaceutical interventions was carried out.
      The study assessed the development of renal function and the effectiveness of
      drug dosage adjustment with pharmacokinetics affected by renal failure in
      patients with creatinine clearance below 30 ml/min. RESULTS: Fifty-two residents
      of 251 centres presented creatinine clearance lower than 30 ml/min. 47 out of 74
      pharmaceutical interventions were accepted. The drugs which were mainly used
      were: diuretics, antibiotics, anti-inflammatories, antiemetics and ranitidine.
      Although the process of renal disease continued its course, in most cases the
      follow-up parameters of effectiveness and safety (in terms of renal toxicity)
      were maintained within the established limits. CONCLUSION: The interventions
      carried out showed, in most cases, to be safe (renal toxicity) and effective,
      with some exceptions which required more individual follow-up.

PMID- 19401098
TI  - [Work of a multidisciplinary team in the control of the prescription of
      ertapenem].
AB  - OBJECTIVE: To determine the effectiveness of the intervention of a
      multidiscipline antimicrobial control group in the correct prescription of
      Ertapenem. METHOD: A four-month long, prospective study into prescriptions for
      Ertapenem was carried out in a third-level hospital. Assessment into the degree
      of suitability of each prescription according to the infections commission usage
      criteria. In the situation where prescriptions were not suitable, recommendations
      were given and acceptance of this was recorded. The effectiveness of the
      antimicrobial treatment used was assessed and treatment was considered effective
      when there was remission of the signs and symptoms of the infection when the
      treatment was completed. The treatment was considered to have failed when the
      signs and symptoms of infection persisted or progressed, requiring the addition
      of another antimicrobial agent, changing antibiotics or the prolongation of the
      treatment for longer than 2 weeks. Lastly, the differences in the average length
      of stay and the duration of the antibiotic treatment between groups were
      analysed. RESULTS: Forty-eight prescriptions were assessed. The usage criterion
      was adequate in 48 % of cases, with 78 % effectiveness in this group. In the
      cases where the prescription was not adequate, but a change in prescription was
      accepted, the effectiveness was 92 %, with 55.5 % of those cases not accepting
      recommendation for change. The average stay was higher in this last group (p =
      0.07). The duration of the antibiotic treatment in the patients who accepted the
      change in prescription was significantly less than in those who did not accept it
      (2 vs 7.4 days, p < 0.0001). CONCLUSIONS: The control of Ertapenem prescriptions
      by a multidisciplinary team was effective.

PMID- 19401099
TI  - [Erythrodermia induced by zolpidem: case description].

PMID- 19401100
TI  - [Vancomycin or linezolid as the treatment of choice for grampositive nosocomial
      pneumonia].

PMID- 19401101
TI  - [Clinical pharmacokinetics in Spain].

PMID- 19401102
TI  - [Neurotoxicity associated with lithium salts].

PMID- 19401104
TI  - [On the efficiency of continuing education].

PMID- 19401105
TI  - [Decision on the time for post-operative extubation of maxillofacial surgery
      patient in the intensive care unit].
AB  - OBJECTIVE: Evaluate moment of extubation in maxillofacial post-operative patients
      admitted to an intensive care unit (ICU) and analyze early complications during
      their stay. DESIGN: An observational and prospective study. SETTING: Third level
      hospital ICU. PATIENTS AND METHODS: All patients we underwent maxillofacial
      surgery and admitted to the ICU for immediate post-operative care from February
      2007 to March 2008 were studied. Demographic and clinical data variables of the
      patients, anesthesic variables prior to surgery and mechanical ventilation and
      postoperative complications during their stay in the ICU were recorded. RESULTS:
      A total of 102 patients were collected during the study. Of these, 58 (55.8%)
      patients were extubated early (within the first 4 hours of admission). Global
      rate of complications was 12.5%. Length of mechanical ventilation was longer in
      patients who required cervical lymph node extraction (p = 0.0031). We found an
      association between complications and late extubation (p = 0.034; OR = 3.78; 95%
      CI, 1.16-12.31). The multivariant study showed that late extubation and surgery
      that required lymph node extraction are predictors of complications. CONCLUSIONS:
      In our series, late extubation and the need for cervical lymph node extraction
      were independent risk factors for complications in ICU. Although early extubation
      may be hazardous in some cases in the first hours, we have no consistent data to
      maintain mechanical ventilation longer than needed to recover from the
      anesthesia.

PMID- 19401106
TI  - [Tracheal intubation guided by fibrobronchoscopy in patients with difficult
      airway. Predictive factors of the outcome].
AB  - INTRODUCTION AND OBJECTIVE: Tracheal intubation (TI) guided by fibrobronchoscopy
      (FB) is one of the essential techniques in the approach to the difficult airway
      (DAW). Few works have been published on the possible causes of TI failure with
      this procedure. This study aims to discover which factors could predict TI
      failure with FB. MATERIAL AND METHODS: An observational and retrospective study
      in which the last 122 consecutive TIs guided by FB (between January 2000 and
      April 2008) performed by our group were included. A multivariate analysis of the
      factors that could influence in the outcome was conducted: cause of the DAW, TI
      pathway, type of endotracheal tube, elective or urgent indication of the
      procedure, sedation level and experience of the bronchoscopist. RESULTS: Tracheal
      intubation in individuals who are going to undergo surgical interventions
      accounts for 92.6% of the total. The most frequent indications of TI by FB were:
      limitation of neck movement (60 cases), airway stenosis (24), increase of soft
      tissues (13), narrow oral aperture (9), airway compression (6), and vocal cord
      paralysis (6). In 10 (8.2%) cases, TI by FB was not possible. The variables that
      best predicted IT failure in the multivariate analysis were profound sedation/
      general anesthesia (OR = 12.2; 95% CI, 1.8-84; p = 0.01) and limited experience
      of the bronchoscopist (OR = 25.3; 95% CI, 3.5-181.8; p = 0.001). CONCLUSIONS: TI
      guided by FB performed by bronchoscopist is successful in more than 90% of the
      cases with DAW. The skill and experience of the bronchoscopist is one of the
      primary determining factors of success of the procedure. Profound sedation may
      condition TI guided by FB failure.

PMID- 19401107
TI  - [Role of decompressive craniectomy in brain injury patient].
AB  - Second level therapeutic maneuvres for controlling intracranial hypertension
      (ICH) proposed by the European Brain Injury Consortium and the American
      Association of Neurological Surgeons include barbiturates, moderate hypothermia
      and decompressive craniectomy (DC). However, neither barbiturates nor hypothermia
      have been demonstrated to improve its outcome. DC could be a therapeutic option
      in the management of ICH without intracerebral masses. Therefore, our goal has
      been to review and analyze the clinical usefulness of DC in patients with brain
      injury in an attempt to deal with some concerns of the critical care physicians.
      Can DC improve patient outcome? Currently, there are no randomized and controlled
      clinical trials supporting or rejecting the practice of DC in adults. Most
      published reports provide level II of evidence. However, most of those studies
      have shown that the outcome is better in patients with DC. When should DC be
      performed? It should be performed early to prevent ICH from occurring more than
      12 hours. What are the effects of DC on intracranial pressure and brain
      oxygenation? In most patients, ICP can be maintained below 25 mmHg after a DC.
      However, to improve brain oxygenation (PtiO(2)), the probe must be placed in the
      healthy area of the most severely damaged cerebral hemisphere. What is the
      suggested surgical procedure? Frontal-subtemporal-parietal-occipital
      craniectomies, including enlargement of the dura by duroplasty. And finally, what
      are the current contraindications of DC? Glasgow Coma Scale score 3 points post
      resuscitation states with dilated and arreactive pupils, age > 65 years old, ICH
      > 12 hours, persistent (a-yv)DO(2) < 3.2% or PtiO(2) < 10 mmHg maintained from
      the moment of admission.

PMID- 19401108
TI  - [The challenge of Web 2.0-based <<virtual ICU>>].
AB  - Intensive medicine has the opportunity to create an interactive virtual community
      using Web 2.0. The main feature of this new web generation is to convert the user
      into an active element of the virtual world, allowing the passive, information
      searching user to become one who creates, shares, participates and closely
      relates to it. These features make it possible for the clinical sphere, the
      researcher and the innovator to coincide, thus providing interaction not only
      among the members of the virtual community but also with citizens and patients.
      The creation of a Web 2.0-based <<Virtual ICU>> represents an opportunity for
      improvement as well as an added value for intensive medicine.

PMID- 19401109
TI  - [Intermittent versus continuous renal replacement techniques: pro continuous].

PMID- 19401110
TI  - [Intermittent versus continuous renal replacement techniques: pro intermittent].
AB  - After an introduction that summarizes the new definitions and risk classification
      of acute kidney injury, along with the consequences on its epidemiology,
      available evidence in the literature is reviewed in order to compare intermittent
      and continuous renal replacement therapy in terms of survival, renal function
      recovery, hemodynamic stability, transferences between the different techniques
      and major complications.

PMID- 19401112
TI  - [Some uncommon applications of transcranial Doppler in the intensive care unit].
AB  - We present the case of a 64-year old woman with shock related to ischemic colitis
      associated with paradoxical embolism through a foramen ovale. Some utilities of
      transcranial Doppler ultra-sonography applied in this case that could have an
      usual interest in intensive and intermediate care are discussed. These include
      analysis of the regional distribution of cerebral blood flow, intracranial
      arterial continuous monitoring for detection of spontaneous microembolisms and
      injection of microbubbles to detect right to left shunts. The added value of
      using power M-mode Doppler in transcranial Doppler evaluations is highlighted.

PMID- 19401113
TI  - [Severe neutropenia and acute respiratory distress syndrome secondary to
      Plasmodium vivax].

PMID- 19401114
TI  - [On calibration of prediction of death in critical patients].

PMID- 19401116
TI  - [Calcium sign].

PMID- 19401117
TI  - Diabetics and drug-eluting stents in ST segment elevation myocardial infarction:
      confidence in numbers.

PMID- 19401118
TI  - Studies of gene polymorphisms and myocardial infarction. an endangered species?

PMID- 19401119
TI  - Diagnosing ischemia with vasodilatatory stress cardiac magnetic resonance: the
      benefit of a comprehensive approach.

PMID- 19401120
TI  - Drug-eluting stents versus bare-metal stents in diabetic patients with ST-segment
      elevation acute myocardial infarction: a pooled analysis of individual patient
      data from seven randomized trials.
AB  - INTRODUCTION AND OBJECTIVES: The performance of drug-eluting stents (DESs) in
      high-risk patients with diabetes and acute ST-elevation myocardial infarction
      (STEMI) who have undergone primary angioplasty has not been previously studied.
      The objective was to evaluate the efficacy and safety of DESs in diabetic
      patients with STEMI. METHODS: We performed a pooled analysis of individual
      patient data from seven randomized trials that compared DESs (i.e., sirolimus- or
      paclitaxel-eluting stents) with bare-metal stents (BMSs) in patients with STEMI.
      The analysis involved 389 patients with diabetes mellitus from a total of 2476
      patients. The outcomes of interest were target-lesion revascularization, stent
      thrombosis, death and the composite endpoint of death or recurrent myocardial
      infarction during a follow-up of 12-24 months. RESULTS: Overall, 206 diabetic
      patients received a DES and 183, a BMS. The risk of target-lesion
      revascularization was significantly lower in patients treated with a DES compared
      to those treated with a BMS (hazard ratio [HR] 0.44, 95% confidence interval [CI]
      0.23-0.88; P=.02). There was no significant difference in the risk of stent
      thrombosis between those treated with a DES or a BMS (HR 0.33, 95% CI 0.09-1.13;
      P=.08). Similarly, the risk of the combined endpoint of death or myocardial
      infarction was not significantly different between patients treated with a DES or
      a BMS (HR 0.64, 95% CI 0.36-1.13; P=.12). CONCLUSIONS: Compared with BMSs, DES
      use improved clinical outcomes in diabetic patients undergoing primary
      angioplasty for STEMI: the need for reintervention was reduced, with no increase
      in mortality or myocardial infarction.

PMID- 19401121
TI  - Association of the plasminogen activator inhibitor-1 gene 4G/5G polymorphism with
      ST elevation acute myocardial infarction in young patients.
AB  - INTRODUCTION AND OBJECTIVES: To investigate the role of the 4G/5G polymorphism in
      the plasminogen activator inhibitor-1 (PAI-1) gene in patients with ST-elevation
      myocardial infarction (STEMI) aged < or =45 years and its influence on regulation
      of the plasma PAI-1 concentration. METHODS: This case-control study included 127
      consecutive patients aged < or =45 years with a diagnosis of STEMI who were
      admitted to a cardiovascular intensive care unit and 127 controls recruited
      between January 2006 and March 2007. Participants were genotyped for the 4G/5G
      polymorphism using the polymerase chain reaction and restriction fragment length
      polymorphism analysis, and their plasma PAI-1 concentrations were measured.
      Informed consent was obtained from all participants. RESULTS: There was a
      significant difference in genotype distribution between the two groups (P< .002).
      The 4G allele occurred more frequently in the patient group (P=.032). In
      addition, there were significant independent associations between STEMI and the
      4G allele (i.e., 4G/4G plus 4G/5G; odds ratio [OR]=2.29; 95% confidence interval
      [CI], 1.12-4.68; P=.022), smoking (OR=23.23; 95% CI, 8.92-60.47; P< .001), a
      family history of cardiovascular disease (OR=4.66; 95% CI, 2.06-10.52; P=.001)
      and hypertension (OR=5.42; 95% CI, 1.67-17.56; P=.005). The plasma PAI-1
      concentration was higher in individuals who were homozygous for the 4G allele (P<
      .001). CONCLUSIONS: The study findings indicate that the 4G allele is an
      independent risk factor for acute myocardial infarction in young patients, as are
      smoking, hypertension and a family history of inherited cardiovascular disease.

PMID- 19401122
TI  - Oxidized LDL, lipoprotein (a) and other emergent risk factors in acute myocardial
      infarction (FORTIAM study).
AB  - INTRODUCTION AND OBJECTIVES: To determine the prevalence of acute myocardial
      infarction (AMI) without classical risk factors, and to ascertain whether
      affected patients exhibit a higher prevalence of emergent risk factors and
      whether the presence of specific emergent risk factors influence prognosis at 6
      months. METHODS: The FORTIAM (Factores Ocultos de Riesgo Tras un Infarto Agudo de
      Miocardio) study is a multicenter cohort study that includes 1371 AMI patients
      who were admitted within 24 hours of symptom onset. Strict definitions were used
      for classical risk factors and the concentrations of the following markers were
      determined: lipoprotein (a) [Lp(a)], oxidized low-density lipoprotein (oxLDL),
      high-sensitivity C-reactive protein, fibrinogen, homocysteine and antibody to
      Chlamydia. The end-points observed during the 6-month follow-up were death,
      angina and re-infarction. RESULTS: The prevalence of AMI without classical risk
      factors was 8.0%. The absence of classical risk factors did not affect the 6
      month prognosis. The only emergent risk factors independently associated with a
      poorer prognosis were the Lp(a) and oxLDL concentrations. Cut-points were
      determined using smoothing splines: 60 mg/ dL for Lp(a) and 74 U/L for oxLDL. The
      associated hazard ratios, adjusted for age, sex and classical risk factors, were
      1.40 (95% confidence interval, 1.06-1.84 ) and 1.48 (95% confidence interval,
      1.06-2.06), respectively. CONCLUSIONS: The proportion of AMI patients without
      classical risk factors was low and their prognosis was similar to that in other
      AMI patients. Both oxLDL and Lp(a) concentrations were independently associated
      with a poorer 6-month prognosis, irrespective of the presence of classical risk
      factors.

PMID- 19401124
TI  - Experimental study of the so called left ventricular isovolumic relaxation phase.
AB  - INTRODUCTION AND OBJECTIVES: Left ventricular filling begins in the ventricular
      isovolumic relaxation phase. According to the Torrent-Guasp myocardial band
      theory, this phase results from the contraction of the final portion of the
      myocardial band: the ascending segment of the apical loop. The objectives were to
      study the myocardial mechanisms influencing transmitral flow during early
      diastole and to determine whether the rapid ventricular filling phase involves
      contraction or relaxation. METHODS: An experimental in vivo pig model was used.
      Regional contractility in three segments of the myocardial band was assessed
      using piezoelectric crystals and mitral flow was measured by echo-Doppler
      ultrasonography at baseline and after akinesia had been induced in the ascending
      segment by 2.5% formaldehyde infusion. Changes in intracavitary pressure in the
      left ventricle and left atrium and flow alterations in the aortic root were
      recorded. The start of the isovolumic relaxation phase was identified using the
      time at which the ejection of blood ceases, as indicated by aortic flow
      measurements. RESULTS: During the left ventricular isovolumetric relaxation
      phase, the ascending segment of the apical loop was undergoing contraction. The
      infusion of formaldehyde into this segment affected the extent to which the
      intraventricular pressure could decrease, prolonged the isovolumic relaxation
      phase and resulted in a lower minimum pressure. It also produced a significant
      decrease in transmitral flow velocity in early diastole and an increase at end
      diastole. CONCLUSIONS: The rapid ventricular filling phase is characterized by
      contraction.

PMID- 19401123
TI  - Additional diagnostic value of systolic dysfunction induced by dipyridamole
      stress cardiac magnetic resonance used in detecting coronary artery disease.
AB  - INTRODUCTION AND OBJECTIVES: Dipyridamole stress perfusion cardiovascular
      magnetic resonance (CMR) is used to detect coronary artery disease (CAD).
      However, few data are available on the diagnostic value of the systolic
      dysfunction induced by dipyridamole. This study investigated whether the
      induction of systolic dysfunction supplements the diagnostic information provided
      by perfusion imaging in the detection of CAD. METHODS: Overall, 166 patients
      underwent dipyridamole CMR and quantitative coronary angiography, with CAD being
      defined as a stenosis > or =70%. Systolic dysfunction at rest, systolic
      dysfunction with dipyridamole, induced systolic dysfunction, and stress first
      pass perfussion deficit (PD) and delayed enhancement were quantified. RESULTS: In
      the multivariate analysis, PD (hazard ratio [HR]=1.6; 95% confidence interval
      [CI], 1.33-1.91;P< .0001) and induced systolic dysfunction (OR=1.8; 95% CI, 1.18
      2.28; P< .007) were independently associated with CAD and had a sensitivity and
      specificity of 92% and 62% and 43% and 96%, respectively. Patients were
      categorized as having no ischemia (Group 1), PD but no induced systolic
      dysfunction (Group 2), or induced systolic dysfunction irrespective of PD (Group
      3). In Group 3, the prevalence of CAD was higher than in Group 1 or 2 (96% vs.
      22% and 79%, respectively; P=.001) and the risk of CAD was two-fold higher than
      in Group 2 (OR=2.34; 95% CI, 1.07-5.13; P=.034). Compared with Group 2, more
      hypoperfused segments were observed in Group 3 (6.2+/-2.6 vs. 7.4+/-3.4; P=.044),
      and more diseased vessels (1.4+/-1.0 vs. 1.8+/-0.9; P=.036). Adding induced
      systolic dysfunction to perfusion and clinical data improved the multivariate
      model's C-statistic for predicting CAD (0.81 vs. 0.87; P=.02). CONCLUSIONS:
      Combining induced systolic dysfunction with perfusion imaging increases the
      diagnostic accuracy of detecting CAD and enables patients with severe ischemia
      and a high probability of CAD to be identified.

PMID- 19401125
TI  - Randomized clinical trial of the effectiveness of a home-based intervention in
      patients with heart failure: the IC-DOM study.
AB  - INTRODUCTION AND OBJECTIVES: The objective of this study was to determine whether
      a home-based intervention can reduce mortality and hospital readmissions and
      improve quality of life in patients with heart failure. METHODS: A randomized
      clinical trial was carried out between January 2004 and October 2006. In total,
      283 patients admitted to hospital with a diagnosis of heart failure were randomly
      allocated to a home-based intervention (intervention group) or usual care
      (control group). The primary end-point was the combination of all-cause mortality
      and hospital readmission for worsening heart failure at 1-year follow-up.
      RESULTS: The primary end-point was observed in 41.7% of patients in the
      intervention group and in 54.3% in the control group. The hazard ratio was 0.70
      (95% confidence interval [CI] 0.55-0.99). Taking significant clinical variables
      into account slightly reduced the hazard ratio to 0.62 (95% CI 0.50-0.87). At the
      end of the study, the quality of life of patients in the intervention group was
      better than in the control group (18.57 vs. 31.11; P< .001). CONCLUSIONS: A home
      based intervention for patients with heart failure reduced the aggregate of
      mortality and hospital readmissions and improved quality of life.

PMID- 19401126
TI  - End-stage heart disease in the elderly.
AB  - This document was produced by the Spanish Society of Cardiology Section on
      Geriatric Cardiology "End-stage heart disease in the elderly" working group. Its
      aim was to provide an expert overview that would increase understanding of the
      last days of life of elderly patients with heart disease and improve treatment
      and clinical decision-making. As elderly heart disease patients form a
      heterogeneous group, thorough clinical evaluation is essential, in particular to
      identify factors that could influence prognosis (e.g., heart disease, comorbid
      conditions, functional status and frailty). The evaluation should be carried out
      before any clinical decisions are made, especially those that could restrict
      therapy, such as do-not-resuscitate orders or instructions to deactivate an
      implantable cardioverter-defibrillator. Elderly patients with terminal heart
      disease have the right to expect a certain level of care and consideration: they
      should not suffer unnecessarily, their freely expressed wishes should be
      respected, they should be fully informed about their medical condition, they
      should be able to express an opinion about possible interventions, and they
      should be entitled to receive psychospiritual care. After an incurable disease
      has been diagnosed, the aim of palliative care should be to control symptoms. It
      should not be used only when the patient is close to death. Although palliative
      care is relatively undeveloped in heart disease, its use must be borne in mind in
      elderly patients with advanced heart failure. The main aims are to make the
      patient as comfortable as possible in all senses and to optimize quality of life
      in the patient's final days, while avoiding the use of aggressive treatments that
      consume health-care resources without providing any benefits.

PMID- 19401127
TI  - Cardiovascular translational medicine (IV): The genetic basis of malignant
      arrhythmias and cardiomyopathies.
AB  - The remarkable advances that have taken place in biomedicine over the past 50
      years have resulted in dramatic improvements in the prevention, diagnosis and
      treatment of many diseases. Although cardiology has adopted these advances at a
      relatively slow pace, today it is fully immersed in this revolution and has
      become one of the most innovative medical specialties. Research is continuing to
      give rise to new developments in genetics and molecular biology that lead, almost
      daily, to innovative ways of preventing, diagnosing and treating the most severe
      forms of heart disease. Consequently, it is essential that clinical cardiologists
      have some basic knowledge of genetics and molecular biology as these disciplines
      are having an increasing influence on clinical practice.

PMID- 19401128
TI  - Where does the right coronary artery originate?

PMID- 19401129
TI  - Percutaneous treatment of mitral valve periprosthetic leakage. An alternative to
      high-risk surgery?
AB  - Periprosthetic mitral valve regurgitation due to paravalvular leakage is one of
      the complications of valve replacement surgery. We report a series of eight
      patients with severe symptomatic periprosthetic mitral regurgitation in whom
      surgery could not be performed because of the high risk. All patients were
      assigned to percutaneous closure of periprosthetic mitral valve leaks using an
      Amplatzer duct occluder. The procedure was successful in five patients. A
      significant reduction in periprosthetic regurgitation and a clinical improvement
      were observed in four of the patients. The procedure was unsuccessful in three
      patients: in two due to interference with the prosthesis discs; in the other,
      because it was not possible to pass through the leak. One of these three patients
      died a few hours after the procedure due to severe stroke. Percutaneous closure
      of paravalvular leakage in patients at a high surgical risk is technically
      feasible and has an acceptable clinical success rate.

PMID- 19401130
TI  - Closure of perivalvular leaks using an Amplatzer occluder.
AB  - Reoperation of patients with perivalvular leaks due to heart failure or hemolysis
      is associated with increased morbidity and mortality. Percutaneous closure using
      an Amplatzer device offers a promising alternative. We describe our initial
      experience between 2004 and 2006, during which we used an Amplatzer device in
      eight patients for the percutaneous closure of perivalvular leaks (four aortic
      and four mitral). The patients were all symptomatic and had a high surgical risk.
      Device placement was successful in all patients with mitral leaks and in three
      with aortic leaks. There were no periprocedural complications. With four of the
      seven (57%) device placements, there was a significant reduction in the degree of
      regurgitation and, at 12-month follow-up, only these four patients showed
      clinical improvements. Of the other three, one required reoperation and two died
      of non-cardiovascular causes. Percutaneous closure of perivalvular leaks was
      feasible and safe and can be regarded as a treatment option in patients with a
      high surgical risk.

PMID- 19401131
TI  - Brief smoking cessation intervention in hospitalized patients with cardiovascular
      disease.
AB  - The objective of this study was to determine the smoking abstinence rate after
      hospital discharge in cardiovascular patients who had undergone a brief smoking
      cessation intervention during hospitalization. The prospective cohort study
      involved 252 smokers who were admitted to the Hospital Universitari de Bellvitge
      in Catalonia, Spain. Twenty-four hours after hospital discharge, 76.6% of
      patients were still abstaining from smoking. At 1, 3, 9 and 12 months, the
      abstinence rate diminished to 71.4%, 67.2%, 64.1% and 62.2%, respectively.
      Patients diagnosed with ischemic cardiopathy had a significantly lower
      probability of a smoking relapse: hazard ratio=0.56 (95% confidence interval,
      0.36-0.87). At our center, a brief smoking cessation intervention in
      cardiovascular patients during hospital admission was found unlikely to result in
      smoking abstinence following discharge.

PMID- 19401132
TI  - Mycotic axillary artery aneurysm.

PMID- 19401133
TI  - Prosthetic mitral valve thrombosis treated with two consecutive courses of
      fibrinolysis.

PMID- 19401134
TI  - Medication adherence in patients with heart failure and a depressed ejection
      fraction attending cardiology clinics.

PMID- 19401135
TI  - Reflections on beta-adrenergic receptor blockers and cocaine use. A case in
      point.

PMID- 19401136
TI  - Current role of electrocardiography in acute ischemic syndromes: is it an
      outdated technique?

PMID- 19401137
TI  - Ventricular tachycardia due to marijuana use in a heart transplant patient.

PMID- 19401138
TI  - QT-interval dispersion and myocardial viability.

PMID- 19401141
TI  - An AC-5 cathepsin B-like protease purified from Haemonchus contortus excretory
      secretory products shows protective antigen potential for lambs.
AB  - The immunogenic properties of cysteine proteases obtained from
      excretory/secretory products (ES) of Haemonchus contortus were investigated with
      a fraction purified with a recombinant H. contortus cystatin affinity column. The
      enrichment of H. contortus ES for cysteine protease was confirmed with substrate
      SDS-PAGE gels since the cystatin-binding fraction activity was three times higher
      than total ES, despite representing only 3% of total ES. This activity was
      inhibited by a specific cysteine protease inhibitor (E64) and by recombinant
      cystatin. The one-dimensional profile of the cystatin-binding fraction displayed
      a single band with a molecular mass of 43 kDa. Mass spectrometry showed this to
      be AC-5, a cathepsin B-like cysteine protease which had not been identified in ES
      products of H. contortus before. The cystatin binding fraction was tested as an
      immunogen in lambs which were vaccinated three times (week 0, 2.5 and 5),
      challenged with 10 000 L3 H. contortus (week 6) before necropsy and compared to
      unvaccinated challenge controls and another group given total ES (n = 10 per
      group). The group vaccinated with cystatin-binding proteins showed 36% and 32%
      mean worm burden and eggs per gram of faeces (EPG) reductions, respectively,
      compared to the controls but total ES was almost without effect. After challenge
      the cystatin-binding proteins induced significantly higher local and systemic ES
      specific IgA and IgG responses.

PMID- 19401142
TI  - Distinct spatial activation of intrinsic and extrinsic apoptosis pathways in
      natural scrapie: association with prion-related lesions.
AB  - Neurodegeneration and gliosis are the main neuropathological features of prion
      diseases. However, the molecular mechanisms involved in these processes remain
      unclear. Several studies have demonstrated changes in the expression of apoptotic
      factors and inflammatory cytokines in animals with experimental infection. Here
      we present the expression profiles of 15 genes implicated in the intrinsic and
      extrinsic apoptotic pathways in the central nervous systems of sheep naturally
      infected with scrapie. Expression changes obtained by real-time RT-PCR were also
      compared with the extent of classical scrapie lesions, such as prion deposition,
      neuronal vacuolisation, spongiosis, and astrogliosis as well as with the
      activation of caspase-3, using a stepwise regression. The results suggest that
      the factors assessed participate in apoptotic or inflammatory functions,
      depending on the affected area. The mitochondrial apoptosis pathway was
      associated with prion deposition in the prefrontal cortex (the less affected
      area), and with activation of caspase-3-mediated cell death via over-expression
      of BAK. In addition to its known association with astroglial activation, the
      extrinsic apoptosis pathway was also related to cell death and neuronal
      vacuolisation.

PMID- 19401144
TI  - Role of non-neuronal nicotinic acetylcholine receptors in angiogenesis.
AB  - Angiogenesis is a critical physiological process for cell survival and
      development. Endothelial cells, necessary for the course of angiogenesis, express
      several non-neuronal nicotinic acetylcholine receptors (AChRs). The most
      important functional non-neuronal AChRs are homomeric alpha7 AChRs and several
      heteromeric AChRs formed by a combination of alpha3, alpha5, beta2, and beta4
      subunits, including alpha3beta4-containing AChRs. In endothelial cells, alpha7
      AChR stimulation indirectly triggers the activation of the integrin alphavbeta3
      receptor and an intracellular MAP kinase (ERK) pathway that mediates
      angiogenesis. Non-selective cholinergic agonists such as nicotine have been shown
      to induce angiogenesis, enhancing tumor progression. Moreover, alpha7 AChR
      selective antagonists such as alpha-bungarotoxin and methyllycaconitine as well
      as the non-specific antagonist mecamylamine have been shown to inhibit
      endothelial cell proliferation and ultimately blood vessel formation.
      Exploitation of such pharmacologic properties can lead to the discovery of new
      specific cholinergic antagonists as anti-cancer therapies. Conversely, the pro
      angiogenic effect elicited by specific agonists can be used to treat diseases
      that respond to revascularization such as diabetic ischemia and atherosclerosis,
      as well as to accelerate wound healing. In this mini-review we discuss the
      pharmacological evidence supporting the importance of non-neuronal AChRs in
      angiogenesis. We also explore potential intracellular mechanisms by which alpha7
      AChR activation mediates this vital cellular process.

PMID- 19401143
TI  - Brain activation abnormalities during speech and non-speech in stuttering
      speakers.
AB  - Although stuttering is regarded as a speech-specific disorder, there is a growing
      body of evidence suggesting that subtle abnormalities in the motor planning and
      execution of non-speech gestures exist in stuttering individuals. We hypothesized
      that people who stutter (PWS) would differ from fluent controls in their neural
      responses during motor planning and execution of both speech and non-speech
      gestures that had auditory targets. Using fMRI with sparse sampling, separate
      BOLD responses were measured for perception, planning, and fluent production of
      speech and non-speech vocal tract gestures. During both speech and non-speech
      perception and planning, PWS had less activation in the frontal and
      temporoparietal regions relative to controls. During speech and non-speech
      production, PWS had less activation than the controls in the left superior
      temporal gyrus (STG) and the left pre-motor areas (BA 6) but greater activation
      in the right STG, bilateral Heschl's gyrus (HG), insula, putamen, and precentral
      motor regions (BA 4). Differences in brain activation patterns between PWS and
      controls were greatest in females and less apparent in males. In conclusion,
      similar differences in PWS from the controls were found during speech and non
      speech; during perception and planning they had reduced activation while during
      production they had increased activity in the auditory area on the right and
      decreased activation in the left sensorimotor regions. These results demonstrated
      that neural activation differences in PWS are not speech-specific.

PMID- 19401145
TI  - Revisiting the seed and soil in cancer metastasis.
AB  - Metastasis remains the overwhelming cause of death for cancer patients. During
      metastasis, cancer cells will leave the primary tumor, intravasate into the
      bloodstream, arrest at a distant organ, and eventually develop into gross lesions
      at the secondary sites. This intricate process is influenced by innumerable
      factors and complex cellular interactions described in 1889 by Stephen Paget as
      the seed and soil hypothesis. In this review, we revisit this seed and soil
      hypothesis with an emerging understanding of the cancer cell (i.e. seed) and its
      microenvironment (i.e. soil). We will provide background to suggest that a
      critical outcome of the seed-soil interaction is resistance of the stresses that
      would otherwise impede metastasis.

PMID- 19401146
TI  - Citicoline (CDP-choline): What role in the treatment of complications of
      infectious diseases.
AB  - A dysregulated host immune response, as opposed to the intrinsic virulence of a
      microbial pathogen induces a large part of the pathology seen in infectious
      diseases. However, current therapies are designed to target the pathogen rather
      than the underlying pathogenic mechanisms responsible for the manifestation of
      the pathology. Recent studies have highlighted the role of endothelial cell
      alteration in the pathology induced in sepsis and cerebral malaria. The
      endothelial onslaught described, is similar to that seen during ischemia
      reperfusion in stroke. Protecting endothelial cell membranes during sepsis and
      cerebral malaria, using citicoline in the same way as in stroke, has thus emerged
      as a new strategy that needs to be evaluated urgently. Citicoline is a natural
      compound that is registered for use in ischemic stroke, head trauma and
      neurological disorders. It enters the phosphatidylcholine synthesis pathway as a
      rate-limiting step and is involved in the modulation of a large number of
      metabolic pathways and neurotransmitter levels, and also in the biosynthesis of
      phospholipids in neuronal membranes. This short review highlights the potential
      role of citicoline as part of adjunct therapy in the treatment of infectious
      diseases.

PMID- 19401147
TI  - Protein-protein interactions involving voltage-gated sodium channels: Post
      translational regulation, intracellular trafficking and functional expression.
AB  - Voltage-gated sodium channels (VGSCs), classically known to play a central role
      in excitability and signalling in nerves and muscles, have also been found to be
      expressed in a range of 'non-excitable' cells, including lymphocytes, fibroblasts
      and endothelia. VGSC abnormalities are associated with various diseases including
      epilepsy, long-QT syndrome 3, Brugada syndrome, sudden infant death syndrome and,
      more recently, various human cancers. Given their pivotal role in a wide range of
      physiological and pathophysiological processes, regulation of functional VGSC
      expression has been the subject of intense study. An emerging theme is post
      translational regulation and macro-molecular complexing by protein-protein
      interactions and intracellular trafficking, leading to changes in functional VGSC
      expression in plasma membrane. This partially involves endoplasmic reticulum
      associated degradation and ubiquitin-proteasome system. Several proteins have
      been shown to associate with VGSCs. Here, we review the interactions involving
      VGSCs and the following proteins: p11, ankyrin, syntrophin, beta-subunit of VGSC,
      papin, ERM and Nedd4 proteins. Protein kinases A and C, as well as Ca(2+)
      calmodulin dependent kinase II that have also been shown to regulate
      intracellular trafficking of VGSCs by changing the balance of externalization vs.
      internalization, and an effort is made to separate these effects from the short
      term phosphorylation of mature proteins in plasma membrane. Two further
      modulatory mechanisms are reciprocal interactions with the cytoskeleton and, late
      stage, activity-dependent regulation. Thus, the review gives an updated account
      of the range of post-translational molecular mechanisms regulating functional
      VGSC expression. However, many details of VGSC subtype-specific regulation and
      pathophysiological aspects remain unknown and these are highlighted throughout
      for completeness.

PMID- 19401148
TI  - Transaldolase: from biochemistry to human disease.
AB  - The role of the enzyme transaldolase (TAL) in central metabolism, its biochemical
      properties, structure, and role in human disease is reviewed. The nearly
      ubiquitous enzyme transaldolase is a part of the pentose phosphate pathway and
      transfers a dihydroxyacetone group from donor compounds (fructose 6-phosphate or
      sedoheptulose 7-phosphate) to aldehyde acceptor compounds. The phylogeny of
      transaldolases shows that five subfamilies can be distinguished, three of them
      with proven TAL enzyme activity, one with unclear function, and the fifth
      subfamily comprises transaldolase-related enzymes, the recently discovered
      fructose 6-phosphate aldolases. The three-dimensional structure of a bacterial
      (Escherichia coli TAL B) and the human enzyme (TALDO1) has been solved. Based on
      the 3D-structure and mutagenesis studies, the reaction mechanism was deduced. The
      cofactor-less enzyme proceeds with a Schiff base intermediate (bound
      dihydroxyacetone). While a transaldolase deficiency is well tolerated in many
      microorganisms, it leads to severe symptoms in homozygous TAL-deficient human
      patients. The involvement of TAL in oxidative stress and apoptosis, in multiple
      sclerosis, and in cancer is discussed.

PMID- 19401149
TI  - Native HMGB1 protein inhibits repair of cisplatin-damaged nucleosomes in vitro.
AB  - The high mobility group box (HMGB) 1 protein, one of the most abundant nuclear
      non-histone proteins has been known for its inhibitory effect on repair of DNA
      damaged by the antitumor drug cisplatin. Here, we report the first results that
      link HMGB1 to repair of cisplatin-treated DNA at nucleosome level. Experiments
      were carried out with three types of reconstituted nucleosomes strongly
      positioned on the damaged DNA: linker DNA containing nucleosomes (centrally and
      end-positioned) and core particles. The highest repair synthesis was registered
      with end-positioned nucleosomes, two and three times more efficient than that
      with centrally positioned nucleosomes and core particles, respectively. HMGB1
      inhibited repair of linker DNA containing nucleosomes more efficiently than that
      of core particles. Just the opposite was the effect of the in vivo acetylated
      HMGB1: stronger repair inhibition was obtained with core particles. No inhibition
      was observed with HMGB1 lacking the acidic tail. Binding of HMGB1 proteins to
      different nucleosomes was also analysed. HMGB1 bound preferentially to damage
      nucleosomes containing linker DNA, while the binding of the acetylated protein
      was linker independent. We show that both the repair of cisplatin-damaged
      nucleosomes and its inhibition by HMGB1 are nucleosome position-dependent events
      which are accomplished via the acidic tail and modulated by acetylation.

PMID- 19401150
TI  - Differences in hydroxylation and binding of Notch and HIF-1alpha demonstrate
      substrate selectivity for factor inhibiting HIF-1 (FIH-1).
AB  - FIH-1, factor inhibiting hypoxia-inducible factor-1 (HIF-1), regulates oxygen
      sensing by hydroxylating an asparagine within HIF-alpha. It also hydroxylates
      asparagines in many proteins containing ankyrin repeats, including Notch1-3, p105
      and I?B?. Relative binding affinity and hydroxylation rate are crucial
      determinants of substrate selection and modification. We determined the
      contributions of substrate sequence composition and length and of oxygen
      concentration to the FIH-1-binding and/or hydroxylation of Notch1-4 and compared
      them with those for HIF-1alpha. We also demonstrated hydroxylation of two
      asparagines in Notch2 and 3, corresponding to Sites 1 and 2 of Notch1, by mass
      spectrometry for the first time. Our data demonstrate that substrate length has a
      much greater influence on FIH-1-dependent hydroxylation of Notch than of HIF
      1alpha, predominantly through binding affinity rather than maximal reaction
      velocity. The K(m) value of FIH-1 for Notch1, < 0.2 microM, is at least 250-fold
      lower than that of 50 microM for HIF-1alpha. Site 1 of Notch1-3 appeared the
      preferred site of FIH-1 hydroxylation in these substrates. Interestingly, binding
      of Notch4 to FIH-1 was observed with an affinity almost 10-fold lower than for
      Notch1-3, but no hydroxylation was detected. Importantly, we demonstrate that the
      K(m) of FIH-1 for oxygen at the preferred Site 1 of Notch1-3, 10-19 microM, is an
      order of magnitude lower than that for Site 2 or HIF-1alpha. Hence, at least
      during in vitro hydroxylation, Notch is likely to become efficiently hydroxylated
      by FIH-1 even under relatively severe hypoxic conditions, where HIF-1alpha
      hydroxylation would be reduced.

PMID- 19401151
TI  - The soluble form of the cancer-associated L1 cell adhesion molecule is a pro
      angiogenic factor.
AB  - A soluble form of the L1 cell adhesion molecule (sL1) is released from various
      tumor cells and can be found in serum and ascites fluid of uterine and ovarian
      carcinoma patients. sL1 is a ligand for several Arg-Gly-Asp (RGD)-binding
      integrins and can be deposited in the extracellular matrix. In this study we
      describe a novel function of this physiologically relevant form of L1 as a pro
      angiogenic factor. We demonstrated that the anti-L1 monoclonal antibody (mAb)
      chCE7 binds near or to the sixth Ig-like domain of human L1 which contains a
      single RGD sequence. mAb chCE7 inhibited the RGD-dependent adhesion of ovarian
      carcinoma cells to sL1 and reversed the sL1-induced proliferation, matrigel
      invasion and tube formation of bovine aortic endothelial (BAE) cells. A
      combination of sL1 with vascular endothelial growth factor-A (VEGF-A(165)), which
      is an important angiogenic inducer in tumors, strongly potentiated VEGF receptor
      2 tyrosine phosphorylation in BAE cells. Chick chorioallantoic membrane (CAM)
      assays revealed the pro-angiogenic potency of sL1 in vivo which could be
      abolished by chCE7. These results indicate an important role of released L1 in
      tumor angiogenesis and represent a novel function of antibody chCE7 in tumor
      therapy.

PMID- 19401152
TI  - Evidence for aerobic ATP synthesis in isolated myelin vesicles.
AB  - Even though brain represents only 2-3% of the body weight, it consumes 20% of
      total body oxygen, and 25% of total body glucose. This sounds surprising, in that
      mitochondrial density in brain is low, while mitochondria are thought to be the
      sole site of aerobic energy supply. These data would suggest that structures
      other than mitochondria are involved in aerobic ATP production. Considering that
      a sustained aerobic metabolism needs a great surface extension and that the
      oxygen solubility is higher in neutral lipids, we have focused our attention on
      myelin sheath, the multilayered membrane produced by oligodendrocytes,
      hypothesizing it to be an ATP production site. Myelin has long been supposed to
      augment the speed of conduction, however, there is growing evidence that it
      exerts an as yet unexplained neuro-trophic role. In this work, by biochemical
      assays, Western Blot analysis, confocal laser microscopy, we present evidence
      that isolated myelin vesicles (IMV) are able to consume O(2) and produce ATP
      through the operation of a proton gradient across their membranes. Living optic
      nerve sections were exposed to MitoTracker, a classical mitochondrial dye, by a
      technique that we have developed and it was found that structures closely
      resembling nerve axons were stained. By immunohistochemistry we show that ATP
      synthase and myelin basic protein colocalize on both IMV and optic nerves. The
      complex of data suggests that myelin sheath may be the site of oxygen absorption
      and aerobic metabolism for the axons.

PMID- 19401153
TI  - Activation of phosphatidylinositol 3-kinase is required for tumor necrosis factor
      alpha-induced upregulation of matrix metalloproteinase-9: its direct inhibition
      by quercetin.
AB  - Matrix metalloproteinases (MMPs) are involved in various skin disorders,
      including photoaging, dermatitis, and tumorigenesis. Tumor necrosis factor (TNF)
      alpha is a key proinflammatory cytokine that acts to provoke inflammation,
      proliferation, and tumorigenesis. The present study investigated the possible
      inhibitory effects of red wine polyphenols on TNF-alpha-induced upregulation of
      MMP-9 and on the migratory phenotype of JB6 P+ mouse epidermal (JB6 P+) cells.
      Red wine extract (RWE) and quercetin, which is a major flavonoid present in red
      wine, inhibited significantly the TNF-alpha-induced upregulation of MMP-9 and
      cell migration, whereas resveratrol did not have significant inhibitory effects.
      The inhibitory effects of RWE and quercetin were mediated by suppression of the
      phosphorylation of Akt and the transactivation of activator protein-1 and nuclear
      factor-kappaB, as determined by Western blotting and luciferase assays,
      respectively. Aside from Akt, quercetin had no effect on the phosphorylation of
      other mitogen-activated protein kinases. Direct kinase assay data revealed that
      RWE and quercetin inhibited phosphatidylinositol 3-kinase (PI3K) activity. The
      results of direct and cell-based pull-down assays demonstrated that RWE and
      quercetin bound to PI3K, resulting in the inhibition of PI3K activity. Using
      chemical inhibitors, it was confirmed that the PI3K-dependent Akt pathway was
      involved in TNF-alpha-induced MMP-9 upregulation and migration in JB6 P+ cells.
      Collectively, these results indicate that TNF-alpha-induced MMP-9 upregulation
      and the migratory phenotype are associated with the PI3K/Akt pathway, and that
      these effects are inhibited strongly by RWE and quercetin.

PMID- 19401155
TI  - Four and a half LIM domains 1 (FHL1) and receptor interacting protein of 140kDa
      (RIP140) interact and cooperate in estrogen signaling.
AB  - Four and a half LIM domains 1 (FHL1) belongs to a family of LIM-only proteins
      that regulate gene transcription, cell proliferation, differentiation and
      apoptosis. However, the biological function of FHL1 remains largely unknown. We
      used a yeast two-hybrid system and identified receptor interacting protein of
      140kDa (RIP140) as a novel FHL1-binding protein. RIP140 interacted with FHL1 both
      in vitro and in mammalian cells and estrogen enhanced this interaction. All
      domains of FHL1 are required to interact with RIP140. Overexpression of FHL1
      enhanced RIP140 repression of estrogen signaling in breast cancer cells in a
      reporter assay, whereas reduction of endogenous FHL1 with FHL1 small interfering
      RNA abolished this effect. Furthermore, overexpression of the FHL1 deletion
      mutant that lacks the RIP140-binding sites had no effect on RIP140 repression of
      estrogen signaling. Consistent with the results of the reporter assays, FHL1 and
      RIP140 synergistically inhibited the transcription of the estrogen-responsive
      gene pS2. The results presented here suggested the cooperative transcriptional
      regulation of estrogen signaling by FHL1 and RIP140, and might provide a new
      regulation mechanism by which estrogen signaling-related diseases such as breast
      cancer develop.

PMID- 19401154
TI  - A major cathepsin B protease from the liver fluke Fasciola hepatica has atypical
      active site features and a potential role in the digestive tract of newly
      excysted juvenile parasites.
AB  - The newly excysted juvenile (NEJ) stage of the Fasciola hepatica lifecycle occurs
      just prior to invasion into the wall of the gut of the host, rendering it an
      important target for drug development. The cathepsin B enzymes from NEJ flukes
      have recently been demonstrated to be crucial to invasion and migration by the
      parasite. Here we characterize one of the cathepsin B enzymes (recombinant
      FhcatB1) from NEJ flukes. FhcatB1 has biochemical properties distinct from
      mammalian cathepsin B enzymes, with an atypical preference for Ile over Leu or
      Arg residues at the P(2) substrate position and an inability to act as an
      exopeptidase. FhcatB1 was active across a broad pH range (optimal activity at pH
      5.5-7.0) and resistant to inhibition by cystatin family inhibitors from sheep and
      humans, suggesting that this enzyme would be able to function in extracellular
      environments in its mammalian hosts. It appears, however, that the FhcatB1
      protease functions largely as a digestive enzyme in the gut of the parasite, due
      to the localization of a specific, fluorescently labeled inhibitor with an Ile at
      the P(2) position. Molecular modelling and dynamics were used to predict the
      basis for the unusual substrate specificity: a P(2) Ile residue positions the
      substrate optimally for interaction with catalytic residues of the enzyme, and
      the enzyme lacks an occluding loop His residue crucial for exopeptidase activity.
      The unique features of the enzyme, particularly with regard to its specificity
      and likely importance to a vital stage of the parasite's life cycle, make it an
      excellent target for therapeutic inhibitors or vaccination.

PMID- 19401156
TI  - COP-binding sites in p24delta2 are necessary for proper secretory cargo
      biosynthesis.
AB  - The p24 family is thought to be somehow involved in endoplasmic reticulum-to
      Golgi protein transport, and its members are major constituents of transport
      vesicles and bind to the vesicle coat protein complexes COPI and COPII. A subset
      of the p24 proteins (p24alpha(3), -beta(1), -gamma(3) and -delta(2)) is
      upregulated when Xenopus laevis intermediate pituitary melanotrope cells are
      physiologically activated to produce vast amounts of their major secretory cargo,
      the prohormone proopiomelanocortin (POMC). To investigate the role of the COP
      binding motifs of p24 proteins in POMC biosynthesis, we here generated and
      analysed Xenopus with stable, melanotrope cell-specific transgene expression of
      p24delta(2)-GFP mutated in its COPI- or COPII-binding motif. In contrast to what
      has been found previously for wild-type (wt) p24delta(2)-GFP, the p24delta(2)
      mutations prevented the Golgi localisation of the transgene products and caused a
      reduced rate of POMC cleavage, but did not lead to a reduction of the endogenous
      p24 proteins nor to aberrations in POMC glycosylation and sulphation. We conclude
      that p24delta(2) requires the presence of the COPI- and COPII-binding sites to
      allow proper POMC processing. Thus, the p24 proteins fulfil their role in
      secretory protein biosynthesis via COPI- or COPII-coated transport vesicles.

PMID- 19401157
TI  - Comparative expression analysis reveals differences in the regulation of
      intestinal paraoxonase family members.
AB  - The paraoxonase (PON) gene cluster contains three members (PON1, PON2, and PON3),
      located on chromosome 7q21.3-22.1. Until now there has been little insight into
      their regulation in human intestine. This study was designed to determine the
      regulation of PONs by oxidative stress and inflammatory factors. Differentiated
      Caco-2/15 cells, cultured on polycarbonate Transwell filter inserts, exhibited
      transcripts of the 3 PONs whereas Western blot revealed the protein expression of
      PON2 and PON3 only. Iron-ascorbate-mediated lipid peroxidation,
      lipopolysaccharides (LPS), tumor necrosis factor-alpha and interferon-gamma
      induced differential effects on the gene expression and protein mass of PONs. In
      particular, LPS down-regulated PON2 protein expression, which was accompanied
      with decreased levels of IkappaBalpha, the inhibitor of the proinflammatory
      transcription factor nuclear factor-kappa B (NF-kappaB). Selective inactivation
      of NF-kappaB by the action of caffeic acid phenethyl ester (CAPE) partially
      attenuated but did not abolish LPS-triggered decline of PON2. However, the
      combination of CAPE and antioxidants completely abrogated the negative impact of
      LPS on PON2. Therefore, our data indicate that oxidative stress and
      proinflammatory agents selectively affect the expression of PONs. Our findings
      also suggest that both NF-kappaB pathway and lipid peroxidation are implicated in
      LPS-dependent diminution of PON2.

PMID- 19401158
TI  - Differential roles of TLR2 and TLR4 in acute focal cerebral ischemia/reperfusion
      injury in mice.
AB  - Recent studies have shown that Toll-like receptors (TLRs) are involved in
      cerebral ischemia/reperfusion (I/R) injury. This study was to investigate the
      role of TLR2 and TLR4 in acute focal cerebral I/R injury. Cerebral infarct size,
      neurological function and mortality were evaluated. NFsmall ka, CyrillicB binding
      activity, phosphorylation of Ismall ka, CyrillicBalpha, Akt and ERK1/2 were
      examined in ischemic cerebral tissue by EMSA and Western blots. Compared to wild
      type (WT) mice, in TLR4 knockout (TLR4KO) mice, brain infarct size was decreased
      (2.6+/-1.18% vs 11.6+/-1.97% of whole cerebral volume, p<0.05) and neurological
      function was maintained (7.3+/-0.79 vs 4.7+/-0.68, p<0.05). However, compared to
      TLR4KO mice, TLR2 knockout (TLR2KO) mice showed higher mortality (38.2% vs 13.0%,
      p<0.05), decreased neurological function (2.9+/-0.53 vs 7.3+/-0.79, p<0.05) and
      increased brain infarct size (19.1+/-1.33% vs 2.6+/-1.18%, p<0.05). NFsmall ka,
      CyrillicB activation and Ismall ka, CyrillicBalpha phosphorylation were
      attenuated in TLR4KO mice (1.09+/-0.02 and 1.2+/-0.04) compared to TLR2KO mice
      (1.31+/-0.02 and 2.2+/-0.32) after cerebral ischemia. Compared to TLR4KO mice, in
      TLR2KO mice, the phosphorylation of Akt (0.2+/-0.03 vs 0.9+/-0.16, p<0.05) and
      ERK1/2 (0.8+/-0.06 vs 1.3+/-0.17) evoked by cerebral I/R was attenuated. The
      present study demonstrates that TLR2 and TLR4 play differential roles in acute
      cerebral I/R injury. Specifically, TLR4 contributes to cerebral I/R injury, while
      TLR2 appears to be neuroprotective by enhancing the activation of protective
      signaling in response to cerebral I/R.

PMID- 19401159
TI  - Nuclear contrast angiography: a simple method for morphological characterization
      of cerebral arteries.
AB  - Visualization of the cerebral vascular tree is important in experimental stroke
      and cerebral vascular malformation research. We describe a simple method, nuclear
      contrast angiography, that enables simultaneous visualization of the arterial
      tree and cerebral endothelial cells in rodent brain whole mounts. A mixture of
      latex and black ink was injected into the arterial system of rodents, resulting
      in high contrast demarcation of the arterial tree of the brain. This method
      clearly differentiates arteries from veins. We applied this method to demonstrate
      that 14 days of unilateral carotid artery occlusion induces increases in the
      caliber of (1) bilateral anterior communicating arteries, (2) bilateral anterior
      cerebral arteries, and (3) ipsilateral proximal middle cerebral artery of the
      circle of Willis. Unlike other methods, this procedure selectively stains
      endothelial nuclei of arteries. Thus, cerebral endothelial nuclei can be
      visualized, quantitated, and morphologically characterized at the same time the
      cortical arterial tree is delineated. This method should be useful in studies of
      stroke and cerebral arteriogenesis, which require the accurate assessment of both
      arterial diameters and endothelial cell density.

PMID- 19401160
TI  - Ingestion of amniotic fluid enhances the facilitative effect of VTA morphine on
      the onset of maternal behavior in virgin rats.
AB  - Previous research has shown that injection of morphine into the ventral tegmental
      area (VTA) facilitates the onset of maternal behavior in virgin female rats, and
      injection of the opioid antagonist naltrexone into the VTA disrupts the onset of
      maternal behavior in parturient rats. Placentophagia -- ingestion of placenta and
      amniotic fluid, usually at parturition -- modifies central opioid processes.
      Ingestion of the active substance in placenta and amniotic fluid, Placental
      Opioid-Enhancing Factor (POEF), enhances the hypoalgesic effect of centrally
      administered morphine, and more specifically, enhances delta- and kappa-opioid
      receptor-mediated hypoalgesia and attenuates mu-opioid-receptor-mediated
      hypoalgesia. POEF (in placenta or amniotic fluid) ingestion does not, by itself,
      produce hypoalgesia. In the present study, we tested the hypothesis that
      ingestion of amniotic fluid enhances the facilitative effect of opioid activity
      (unilateral morphine injection) in the VTA on the rate of onset of maternal
      behavior. Virgin female Long-Evans rats were given one intra-VTA injection of
      morphine sulfate (0.0, 0.01, or 0.03 microg, in saline) and an orogastric
      infusion of 0.25 ml amniotic fluid or saline once each day of the first three
      days of the 10-day testing period. Subjects were continuously exposed to foster
      pups that were replaced every 12 h; replacement of pups was followed by a 15-min
      observation period. Maternal behavior latency was determined by the first of two
      consecutive tests wherein the subject displayed pup retrieval, pup licking in the
      nest, and crouching over all foster pups, during the 15-min observation. We
      confirmed the previous finding that the VTA injection, alone, of 0.03 microg
      morphine shortened the latency to show maternal behavior and that 0.0 microg and
      0.01 microg morphine did not. Ingestion of amniotic fluid (and therefore POEF)
      facilitated the onset of maternal behavior in rats receiving an intra-VTA
      microinjection of an otherwise subthreshold dose of morphine (0.01 microg).

PMID- 19401161
TI  - GABA(A) receptors in the lateral hypothalamus as mediators of satiety and body
      weight regulation.
AB  - In the lateral hypothalamus (LH), the inhibitory amino acid neurotransmitter,
      GABA, has had a long-standing presumptive role as an inhibitor of food intake.
      However, minimal investigation has been focused on GABA, especially as compared
      to the attention received by many peptide transmitters. To begin to address this
      deficiency in the understanding of the role of GABA in the LH and feeding, we
      report that antagonism of GABA(A) receptors in the rat LH elicits feeding,
      consistent with previous findings, and provide evidence for the behavioral
      selectivity of this effect. We extend previous findings that activation of LH
      GABA(A) receptors suppresses feeding, in particular by showing that nighttime and
      deprivation-induced eating are dramatically suppressed. Finally, we show that
      chronic activation, but not blockade, of the LH GABA(A) receptors leads to a
      reduction in 24 h food intake with concomitant body weight loss. These data
      collectively suggest that activation of GABA(A) receptors plays a fundamental
      role in controlling food intake and body weight, a role that has previously been
      somewhat underestimated.

PMID- 19401162
TI  - Expression of monocyte chemoattractant protein-1 in the cerebral artery after
      experimental subarachnoid hemorrhage.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that plays an
      important role in the recruitment of macrophages. Although previous studies have
      demonstrated that MCP-1 has been shown to be involved in the damaging
      inflammatory processes associated with stroke, infection, neoplasia, and others
      in the central nervous system, the role of MCP-1 in the cerebral artery after
      experimental subarachnoid hemorrhage (SAH) in rats has been largely unexplored.
      This study was undertaken to investigate the expression of the MCP-1 in SAH model
      and to clarify the potential role of MCP-1 in cerebral vasospasm. A total of 80
      rats were randomly divided into four groups: control group; day 3, day 5, and day
      7 groups. Day 3, day 5, and day 7 groups were all SAH groups. The animals in day
      3, day 5 and day 7 groups were subjected to injection of autologous blood into
      cisterna magna twice on day 0 and day 2 and were killed on days 3, 5, and 7,
      respectively. Cross-sectional area of basilar artery was measured and the MCP-1
      expression was assessed by real-time PCR, Western blot and immunohistochemistry.
      The cross-sectional area of basilar artery was found to be 85,373+/-8794 mum(2)
      in control group, 59,210+/-7281 mum(2) in day 3, 50,536+/-6519 mum(2) in day 5,
      and 66,360+/-7452 mum(2) in day 7, respectively. The basilar arteries exhibited
      vasospasm after SAH and became more severe on day 5. The elevated mRNA and
      protein of MCP-1 were detected after SAH and peaked on day 5. MCP-1 is
      increasingly expressed in a parallel time course to the development of cerebral
      vasospasm in a rat experimental model of SAH and these findings might have
      important implications during the administration of specific MCP-1 antagonists in
      order to prevent or reduce cerebral vasospasm caused by SAH.

PMID- 19401163
TI  - SK-PC-B70M confers anti-oxidant activity and reduces Abeta levels in the brain of
      Tg2576 mice.
AB  - SK-PC-B70M is an oleanolic-glycoside saponin-enriched fraction derived from the
      root of Pulsatilla koreana. Recently, it was reported that hederacolchiside-E is
      an active ingredient of SK-PC-B70M that confers a neuroprotective effect against
      the cytotoxicity induced by Abeta(1-42) in SK-N-SH neuroblastoma cells. SK-PC
      B70M improves scopolamine-induced impairments of spatial working memory in rats.
      In the present study, we investigated whether SK-PC-B70M has a beneficial effect
      on the Tg2576 murine model of Alzheimer's disease. ELISA analysis revealed that
      the levels of soluble and insoluble forms of Abeta(1-42) in Tg2576 mice fed SK-PC
      B70M (2000 ppm) from 11 months to 16 months of age were reduced to, respectively,
      66% and 79% of the control Tg2576 mice. Anti-Abeta antibody-stained brain
      sections of Tg2576 mice with SK-PC-B70M (2000 ppm) consistently showed a
      reduction in plaque formation in the brain. Western blot analyses showed altered
      expressions of various cellular factors, such as up-regulation of transthyretin,
      phospho-ERK, and phospho-CREB in the brain treated with SK-PC-B70M. SK-PC-B70M
      suppressed the neuronal toxicity induced by H(2)O(2) in primary cortical culture.
      Moreover, biochemical and immunohistochemical analyses showed that the levels of
      malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), oxidized by-products of
      lipid peroxidation, were notably reduced in the hippocampus of Tg2576 mice
      treated with SK-PC-B70M compared with the Tg2576 control. These results suggest
      that SK-PC-B70M attenuates AD-like pathology in the brain of Tg2576 mice.

PMID- 19401164
TI  - Association of the adrenergic alpha 2a receptor--1291C/G polymorphism with weight
      change and treatment response to mirtazapine in patients with major depressive
      disorder.
AB  - BACKGROUND: Adrenergic alpha2a receptors (ADRA2A) are expressed in the central
      nervous system and peripheral tissues. The primary mechanism of action of
      mirtazapine is the antagonism of central presynaptic alpha2 receptors.
      Mirtazapine is reportedly associated with weight gain. Our objective was to
      determine whether the ADRA2A -1291C/G polymorphism is associated with weight gain
      and treatment response to mirtazapine in patients with major depressive disorder
      (MDD). METHODS: The ADRA2A -1291C/G polymorphism was analyzed in 314 MDD patients
      and 162 control subjects. All patients were evaluated using the 21-item Hamilton
      Depression Rating Scale at the beginning of the study and at 1, 2, 4, and 8 weeks
      of mirtazapine treatment. RESULTS: No relationship was observed between the
      ADRA2A -1291C/G polymorphism and MDD. No significant difference was found between
      responder and non-responder groups when comparing the ADRA2A genotype
      distribution with treatment response to mirtazapine. Repeated measures ANOVA with
      the last observation carry-forward test indicated that after adjusting for
      baseline body weight, age, and gender, the subjects with the C/C genotype
      exhibited a greater mean body weight gain than the subjects with the C/G or G/G
      genotype after 8 weeks of mirtazapine treatment (p=0.052). CONCLUSIONS: The
      ADRA2A -1291C/G polymorphism does not appear to be a predictor of treatment
      response to mirtazapine. This polymorphism was weakly associated with weight
      change after 8 weeks of mirtazapine treatment. Further investigation is required
      to determine whether other polymorphisms of this gene influence treatment
      response and weight change in patients receiving mirtazapine.

PMID- 19401165
TI  - Children with specific language impairment: the role of prosodic processes in
      explaining difficulties in processing syntactic information.
AB  - Children with specific language impairment (SLI) experience great difficulties in
      language comprehension and/or production whereby the majority of these children
      have particular problems in acquiring syntactic rules. In the speech stream
      boundaries of major syntactic constituents are reliably marked by prosodic cues.
      Therefore, prosodic information provides an important cue for discovering the
      syntactic structure of a language [Jusczyk, P.W., 2002. How infants adapt speech
      processing capacities to native language structure. Curr. Dir. Psychol. Sci. 11,
      15-18.]. Following this, the question is, whether children with SLI differ in the
      processing of syntactic information from normally developing children and to what
      extent this is related to the processing of the inherent prosodic information.
      Children heard either correct sentences or sentences with a word category
      violation (syntactic level) and a joined prosodic incongruity (prosodic level)
      while event-related brain potentials (ERPs) were recorded. Judging the sentence's
      correctness, control children performed better than children with SLI for all
      types of sentences. With respect to the ERPs, control children showed a bilateral
      early starting anterior negativity sustaining into a late anterior negativity and
      a P600 in posterior regions in response to incorrect sentences. Children with SLI
      showed a comparable P600 but unlike the control children there was only a late,
      clearly left lateralized anterior negativity. The complete absence of a right
      anterior negativity in children with SLI suggests that they may not access
      prosodic information in the same way normal children do. The differences in
      prosodic processing may in turn hamper the development of syntactic processing
      skills as indicated by the absence of the syntax-related early left anterior
      negativity.

PMID- 19401166
TI  - The varying effects of short-term and long-term corticosterone injections on
      depression-like behavior in mice.
AB  - Corticosterone, a principal glucocorticoid synthesized in the rodent adrenal
      cortex and secreted in response to stress, is reported to produce a biphasic
      effect on animal behavior. In this study, we determine that corticosterone
      administration produced different effects on depression-like behavior in mice
      depending on the length of time it was administered. In addition, we explored the
      indirect evidence at the cellular and molecular levels in order to support above
      assertion. Male mice received repeated injections of the vehicle and 20 mg/kg of
      corticosterone for 6, 18, and 36 days before being subjected to the forced
      swimming and tail suspension tests. After behavioral tests, we analyzed the
      number of neuron-specific nuclear protein (NeuN)-positive cells in the
      hippocampus, and the levels of two important cytoskeleton proteins, microtubule
      associated protein 2 (MAP2) and neurofilament light chain protein (NF-L). Our
      results showed that 18-day and 36-day corticosterone injections caused increased
      depression-like behavior in male mice and significantly reduced the NF-L protein
      levels in the hippocampal tissues. However, 6-day corticosterone injection
      exhibited an anti-depressant effect accompanied by increased levels of MAP2 and
      NF-L in the hippocampus. Interestingly, no decrement was observed in NeuN
      positive cells in the entire hippocampus throughout the experiments. The results
      support the view that short-term and long-term corticosterone administration
      produce opposite effects on depression-like behavior. Furthermore, the biphasic
      regulation of cytoskeleton proteins in the hippocampus might be a mechanism by
      which corticosterone treatments influence animal behavior.

PMID- 19401169
TI  - The effects of chronic repetitive transcranial magnetic  stimulation on glutamate
      and gamma-aminobutyric  acid in rat brain.
AB  - Recent studies have shown that repetitive transcranial magnetic stimulation
      (rTMS) has therapeutic potential for some neurological and psychiatric disorders.
      However, the neurobiological effects of this tool are not sufficiently explained
      so far, previous research reported that rTMS can change dopamine release, there
      have been few studies to examine a possible effect of rTMS on amino acid
      neurotransmitter. This study aimed to determine the effects of chronic rTMS on
      glutamate and gamma-aminobutyric acid concentration in the rat brain. Sprague
      Dawley rat was subject to 500 pulses of 0.5 Hz rTMS for 15 days, or sham
      stimulation. After last stimulation, glutamate and gamma-aminobutyric acid
      content were measured by high performance liquid chromatography (HPLC). Results
      showed that the content of glutamate and gamma-aminobutyric acid increased
      significantly in hippocampus and striatum after chronic rTMS, but reduced
      significantly in the hypothalamus. These results indicate that chronic rTMS has a
      modulatory effect on the glutamate and gamma-aminobutyric acid systems. This
      change in amino acid neurotransmitter may contribute to its beneficial effects.

PMID- 19401168
TI  - Antitumor effects of polysorbate-80 coated gemcitabine polybutylcyanoacrylate
      nanoparticles in vitro and its pharmacodynamics in vivo on C6 glioma cells of a
      brain tumor model.
AB  - Polybutylcyanoacrylate (PBCA) nanoparticles coated with polysorbate-80 have been
      extensively studied for delivery of drugs into the animal models; however, 1%
      polysorbate-80 coated gemcitabine PBCA nanoparticles (GCTB-PBCA-NPs) remain
      unknown. In this study, we investigated the inhibitory effects of brain targeted
      1% polysorbate-80 coated GCTB-PBCA-NPs on C6 glioma cells in vitro and in vivo.
      GCTB-PBCA-NPs were prepared by emulsion polymerization and freeze drying. C6
      glioma cells treated with 1% polysorbate-80 coated GCTB-PBCA-NPs showed poor
      growth with less cell density and increased detachment. Cell morphology was also
      greatly altered with nuclear vacuoles, ruptured cells and dead cells. Meanwhile,
      by flow cytometry, the numbers of cells treated with 1% polysorbate-80 coated
      GCTB-PBCA-NPs showed increase in G0/G1 phase and decreased in the S phase
      (P<0.01) compared with the blank control. CCK-8 assay also showed that GCTB could
      significantly inhibited cell proliferation in a concentration dependent manner.
      Finally, various preparations were injected (90 mg preparation per kg body
      weight) into the brain tumor model, which was produced after inoculating C6
      glioma cells into Sprague Dawley (SD) rats for 14 days, it was shown that 1%
      polysorbate-80 coated GCTB-PBCA-NPs could significantly extend the survival time
      compared with the saline control (P<0.05). Taken together, 1% polysorbate-80
      coated GCTB-PBCA-NPs can effectively inhibit the growth of C6 glioma cells in
      vitro and enhance antitumor activity on brain tumor in vivo.

PMID- 19401170
TI  - WITHDRAWN: Transplantation of bone mesenchymal stem cells containing the nerve
      growth factor gene in adult rat brain with Fimbria Fornix lesion.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) are a promising source for
      cell-based treatment of brain injury, but the therapy of BMSCs is restricted by
      low cell survival. We examined whether nerve growth factor (NGF) improve BMSCs
      viability in the brain with Fimbria-Fornix lesion (FF). After transduction of NGF
      gene via recombinant retroviral vectors, the rat BMSCs were transformed into the
      NGF-GFP positive BMSCs, nearly 100% of cells expressed NGF. After transplanted
      into basal forebrain of rat with FF, the NGF-GFP positive BMSCs expressed the
      exogenous NGF gene in the host brain, and interesting, the survival number of
      BMSCs in the NGF group was significant more than that of the void plasmid group.
      Furthermore, the number of choline acetyltransferase (ChAT) immunoreactive
      neurons of NGF group was also significant higher than those of the void plasmid
      group (p<0.05) or the PBS group (p<0.01). Performance in the water maze test was
      improved in these rats in NGF group. These results indicate that NGF increased
      BMSCs survival in brain with FF, which results in better improvement of brain
      function than injected with BMSCs alone.

PMID- 19401167
TI  - Effects of two years of conjugated equine estrogens on cholinergic neurons in
      young and middle-aged ovariectomized monkeys.
AB  - The effect of estrogen on the number and size of cholinergic neurons in the basal
      forebrain was examined in surgically menopausal young and middle-aged cynomolgus
      monkeys. Young and middle-aged female monkeys were ovariectomized and treated
      with conjugated equine estrogens (Premarin) at doses that are equivalent to those
      currently prescribed to postmenopausal women. In the medial septum/diagonal band
      (MS/DB), no effect of treatment with Premarin was observed in the cholinergic
      neurons in either ovariectomized young or middle-aged monkeys. However, the
      number and size of cholinergic neurons in the MS/DB of middle-aged monkeys was
      greater than that in the young monkeys. In the nucleus basalis of Meynert (NBM)
      of middle-aged monkeys, the number of cholinergic neurons in the intermediate
      region (Ch4i) was greater in Premarin-treated monkeys as compared to controls and
      numbers of neurons in this region were greater at higher levels of estrogen. No
      effects of estrogen were observed in other NBM regions in the middle-aged monkeys
      and the size of cholinergic neurons was unaffected by Premarin. These findings
      suggest that treatment with Premarin has selective beneficial effects on
      cholinergic neurons in the basal forebrain but that these effects are both age
      and region specific.

PMID- 19401171
TI  - Age- and sex-differences in the nitric oxide synthase expression and dopamine
      concentration in the murine model of Parkinson's disease induced by 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine.
AB  - Parkinson's disease (PD) is an age- and sex-related neurodegenerative disorder of
      unknown aetiology. The involvement of nitric oxide synthase (NOS) in the
      etiopathogenesis of PD is quite well documented. We decided to examine changes in
      dopamine (DA) levels as well as iNOS, nNOS, eNOS mRNA and protein expression in
      the striatum of C57BL male and female (2- and 12-month old) mice in the course of
      PD-related neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). The significantly decreased level of DA was previously
      observed in male than in female, irrespective of age. In young mice the recovery
      of DA was significantly greater in female compared to male mice. On the contrary,
      both in male and female old animals the low concentration of DA was extended up
      to 21 days post MPTP injection. The increases in iNOS protein expression post
      MPTP intoxication occurred more rapidly in male (young and old) than in female
      mice. The pattern of changes in iNOS protein expression was also different in
      young versus aged mice. nNOS protein expression increased earlier in young male
      than young female mice. No changes were observed in eNOS expression. In
      conclusion, our results support the hypothesis of the involvement of iNOS and
      nNOS, but not eNOS in neurodegenerative processes. Our findings suggest that age-
      and sex-differences in DA concentration and iNOS expression as well as sex
      differences of nNOS expression after intoxication may depend on the increased
      susceptibility of males as well as older animals to toxic effect of MPTP and
      aggravated process of recovery in old brains.

PMID- 19401172
TI  - Quality of rearing guides expression of behavioral and neural  seizure phenotypes
      in EL mice.
AB  - The present studies employed behavioral and neural markers of seizure-related
      plasticity to examine the relative contributions of genetic predisposition versus
      rearing environment in generating adult phenotypes in EL mice, a stress-induced
      animal model of epilepsy. Early environment was manipulated by cross-fostering
      pups of the EL strain to a seizure-resistant CD-1 control strain of mouse. The
      impact of changes in rearing quality on growth,exploratory and stress-reactivity
      phenotypes were examined, with a focus on the role of maternal care in shaping
      seizure susceptibility and neural cF os activation. Improvement in maternal care
      imposed by replacing biological EL dams with foster CD-1 mothers was sufficient
      to decrease pup mortality, to increase body weight gain (+0.1 g/day) and to delay
      the onset of seizure susceptibility in EL offspring beyond post-natal day 80-90.
      Moreover,hypoactivity in hippocampus and cortex among EL offspring cross-fostered
      to EL, but not CD-1 control, dams suggests that changes in rearing environment
      were accompanied by enduring changes in brain plasticity. Thus, neural and
      behavioral phenotypes of EL mice are dependent upon post-partum maternal care
      which if systematically enhanced can postpone seizure expression.

PMID- 19401173
TI  - Up-regulation of astrocyte metabotropic glutamate receptor 5 by amyloid-beta
      peptide.
AB  - The effects of amyloid-beta peptide (Abeta) on astrocyte responses to activation
      of mGlu5 receptors have been investigated using calcium imaging. Pre-incubation
      with Abeta1-40 peptide for up to 72 h produced a time- and concentration
      dependent 2-4 fold enhancement in the magnitude of the intracellular calcium
      mobilization response to the group I metabotropic glutamate receptor agonist (S)
      3,5-dihydroxyphenylglycine (DHPG). In contrast, pre-treatment with Abeta1-40 did
      not alter the calcium responses induced by other G protein coupled- or ion
      channel-receptors. Abeta 1-40-enhanced DHPG responses were blocked by the mGlu5
      antagonist MPEP but not by inhibitors of voltage dependent calcium channels or by
      the AMPA/KA receptor antagonist CNQX. Up-regulation of mGlu5 coupled responses
      was associated with significant increases in astrocyte mGlu5 receptor-mRNA and
      protein expression after preincubation with Abeta . The changes observed in vitro
      were consistent with results obtained from human Alzheimer's disease (AD)
      patients.Immunostaining for mGlu5 receptors was increased on astrocytes which
      were colocalized with Abeta plaques in hippocampal tissue from AD patients
      compared to age-matched controls. These results suggest that modulation of mGlu5
      receptors in astrocytes could be an important mechanism in determining the
      progression of pathology in AD.

PMID- 19401174
TI  - gamma-secretase processing of APLP1 leads to the production of a p3-like peptide
      that does not aggregate and is not toxic to neurons.
AB  - The amyloid precursor-like protein-1 (APLP1) is a member of a protein family that
      includes the Alzheimer's disease-associated amyloid precursor protein (APP).
      While much is known about the proteolytic processing of APP, fewer details are
      available about APLP1. Using Chinese hamster ovarian cells stably transfected
      with human APLP1 and a novel juxtamembrane anti-APLP1 antibody, we demonstrate
      the detection of a secreted approximately 3.5 kDa APLP1-derived peptide (ALP-1).
      The production of this peptide is abolished by inhibition of gamma-secretase, but
      not beta-secretase, suggesting that ALP-1 is analogous to the p3 fragment
      produced from APP. However, unlike p3 or Abeta, ALP-1 shows no obvious propensity
      for aggregation and is not toxic to neuronal cells. Moreover, using two distinct
      experimental paradigms, we demonstrate that neither cell-derived nor chemically
      synthesized ALP-1 influences the oligomerization or aggregation of Abeta.

PMID- 19401175
TI  - A novel conjugate of low-molecular-weight heparin and Cu,Zn-superoxide dismutase:
      study on its mechanism in preventing brain reperfusion injury after ischemia in
      gerbils.
AB  - Low-molecular-weight heparin (LMWH) and Cu,Zn-superoxide dismutase (SOD) were
      extensively investigated on preventing brain reperfusion injury after ischemia
      (BRII) in the past few years and both exhibited some advantages as well as limits
      in practice. To explore whether chemical modification for LMWH and SOD can lead
      to improved bioactivity,in our present study, we examined the efficacy of LMWH
      conjugated SOD (LMWH-SOD) in the model of BRII gerbils. Ischemia/reperfusion was
      performed for 5 min by clamping the bilateral common carotid arteries of gerbils.
      LMWH-SOD, SOD and the mixture of LMWH and SOD (LMWH+SOD) were administered
      intravenously to corresponding animals just before ischemia. 24 h after
      reperfusion, serum malondialdehyde (MDA) content and SOD activity were measured,
      the expression of intercellular adhesion molecule-1 (ICAM-1) was examined by
      immunohistochemistry, and the brain sections were processed for Nissl staining
      and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end
      labeling.The results showed that LMWH-SOD significantly lowered MDA content
      (P<0.001, versus SOD and LMWH+SOD) and elevated SOD activity (P<0.05, versus SOD
      and LMWH+SOD) in the serum of BRII gerbils. Immunohistochemical results indicated
      ICAM-1 positive staining was lighter, pyramidal cells of hippocampal CA1 region
      were more regular and the changes in cell edema were minor, and apoptosis of
      hippocampal cells was milder in LMWH-SOD treated animals than in SOD or LMWH+SOD
      treated animals, untreated BRII animals and sham-operated animals. The results
      suggest that the novel LMWH-SOD conjugate can inhibit upregulation of ICAM-1 and
      prevent neuronal cell apoptosis in BRII gerbils, and the LMWH-SOD conjugate has
      better anti-inflammatory and neuroprotective effects in BRII than native SOD and
      the mixture of LMWH and SOD.

PMID- 19401176
TI  - Dexamethasone enhances calcium-activated potassium  channel expression in blood
      brain tumor barrier in a rat brain  tumor model.
AB  - This study was performed to determine whether dexamethasone (DEX) had an effect
      on calcium-activated potassium channels (KCa channels) in blood-brain tumor
      barrier (BTB).Using a rat brain glioma model, we found that the expression of KCa
      channels protein was significantly increased in brain tumor tissue. And
      bradykinin-induced increase of KCa channels protein was further enhanced after
      DEX pretreatment for 3 days. In addition, DEX pretreatment enhanced bradykinin
      mediated up-regulation of the density of IKCa in the rat brain C6 cells in vitro
      BTB. Bradykinin markedly increased BTB permeability independent of DEX
      pretreatment. All of these results strongly suggest that DEX could regulate the
      target in the transcellular pathway of BTB-KCa channels.

PMID- 19401177
TI  - Methanandamide attenuates cocaine-induced hyperthermia in  rats by a cannabinoid
      CB1-dopamine D2 receptor mechanism.
AB  - Evidence implicates anandamide in dopamine-related cocaine function. In the
      present study, we investigated the effect of methanandamide (5 mg/kg, i.p.), a
      stable anandamide analog, on the hyperthermia and hyperactivity induced by a
      fixed dose of cocaine (15 mg/kg,i.p.). Cocaine administered to rats produced
      hyperthermia and hyperactivity whereas methanandamide was ineffective. For
      combined administration, methanandamide attenuated the hyperthermia, but not
      hyperactivity, induced by cocaine. The effect of methanandamide was abolished by
      pretreatment with a cannabinoid CB1 receptor antagonist, SR141716A (5 mg/kg,
      i.p.), or dopamine D2 receptor antagonist, S(-)-raclopride(5 mg/kg, i.p.) but not
      by capsazepine (40 mg/kg, i.p.), a transient receptor potential vanilloid 1
      cation channel antagonist. Methanandamide also attenuated the hyperthermia caused
      by a dopamine D1 receptor agonist, SKF 38393 (10 mg/kg, s.c.), indicating that it
      reduces hyperthermia produced by dopamine D1 receptor activation. URB597 (0.25
      mg/kg, i.p.), an inhibitor of anandamide metabolism, did not alter cocaine
      induced hyperthermia. Our results demonstrate that methanandamide activates
      cannabinoid CB1 receptors to attenuate cocaine-induced hyperthermia, and that
      dopamine D2 receptor activation plays a permissive role in the thermoregulatory
      effects of methanandamide.

PMID- 19401179
TI  - Altered expression of CRMPs in the brain of bovine spongiform encephalopathy
      infected mice during disease progression.
AB  - While recent studies suggest that synaptic alterations are first events in the
      mechanisms of prion-mediated neurodegeneration, little is known on the identity
      of the neuronal plasticity-related genes potentially concerned. Here the
      expression of 4 Collapsin Response Mediator Proteins (CRMPs), a family of signal
      transduction proteins involved in brain development and altered in Alzheimer's
      disease, was studied in the brain of C57Bl/6 mice infected with the BSE strain of
      prion agent, using RT-PCR and Western-blot methods. At the terminal stage of the
      disease, gene expression of each CRMP had decreased, while at the mid-stage of
      the disease only CRMP4 (mRNA and protein) expression had increased, concomitant
      to the start of PrP(Sc) accumulation in the brainstem. Altogether our findings
      picked out originally CRMPs, and especially CRMP4, as potential contributors to
      prion pathogenesis.

PMID- 19401178
TI  - Cortical activity during manual response inhibition guided by color and
      orientation cues.
AB  - It has been suggested that the right inferior frontal gyrus (IFG) plays a
      critical role in manual response inhibition, although neuroimaging studies of
      healthy adults have also reported widespread activations in other cortical
      regions during a variety of response inhibition tasks. We conducted a functional
      magnetic resonance imaging (fMRI) experiment to examine whether the activation of
      the IFG is dependent on the type of visuo-motor associations during response
      inhibition by varying the feature of the stop signal (color vs. orientation) in
      the stop-signal task. Results from 12 subjects showed that the bilateral ventral
      posterior IFG, anterior insula, inferior frontal junction (IFJ), middle temporal
      gyrus (MTG) and fusiform gyrus (FG) are active during response inhibition cued by
      both color and orientation stop signals. While only the MTG showed differential
      activity to the two stop signals, both MTG and FG showed significantly stronger
      activity during successful than unsuccessful stopping of unwanted responses cued
      by orientation and color, respectively. Our findings suggest that the right
      ventral posterior IFG may play a more general role in response inhibition
      regardless of the feature of the visual signal, while successful inhibition may
      depend on efficient processing of the signal.

PMID- 19401180
TI  - Visual information for action planning in left and right congenital hemiparesis.
AB  - Converging evidence suggests that compromised motor abilities in hemiparetic
      cerebral palsy are not solely due to impairments in motor execution, but are also
      related to deficits in action planning. The present study had two aims. First, we
      compared grip planning in a sequential task between participants with left-sided
      (n=12) or right-sided (n=10) congenital hemiparesis. Second, we studied the use
      of visual information for grip planning by having participants grasp a rod
      embedded in a 'rod-and-frame' illusion. The results showed that especially
      participants with right hemiparesis revealed planning problems as most of them
      did not switch between different grip types at all or they switched in an
      inconsistent manner. In contrast, the majority of participants with left
      hemiparesis showed consistent planning of the first part of the task. Second, the
      results indicated that visual information provided by the illusion had an effect
      on grip planning in participants that used a consistent planning strategy,
      suggesting that the use of visual information in action planning was not affected
      in these participants. The results are discussed in relation to hemispheric
      differences in motor planning and visuo-motor integration in congenital
      hemiparesis.

PMID- 19401181
TI  - Optic nerve infarction and post-ischemic inflammation in the rodent model of
      anterior ischemic optic neuropathy (rAION).
AB  - Nonarteritic anterior ischemic optic neuropathy (NAION) results from isolated
      anterior optic nerve (ON)-axonal ischemia near the retina-optic nerve junction.
      We utilized a rodent model of NAION (rAION) to study the in vivo inflammatory
      response after pure axonal ischemic infarct. ON ischemia was generated using
      laser-coupled rose Bengal dye photoactivation, and the infarct localized using
      tetrazolium red and histology. ON inflammation was evaluated following infarct
      using extrinsic macrophage (ED1) and microglial (isolated Iba1) cell markers. In
      naive ONs, some ED1(+)/Iba1(+) cells, representing extrinsic macrophages, were
      present in intraretinal ON region, but not in the retroscleral (isolated ON)
      region. Numerous ED1(-)/Iba1(+) cells, likely representing intrinsic microglia,
      were present throughout the entire ON. One day post-stroke, slight increases in
      both ED1(+) and Iba1(+) cells were apparent in the eye region immediately
      surrounding the anterior ON. Three days post-stroke, there was marked
      infiltration and aggregates of ED1(+)/Iba1(+) cells, with axon structural
      disruption in the region of the ischemic infarct. ED1(+) and Iba1(+) cells were
      present in the portion of the ON surrounding the infarct, possibly representing a
      penumbral region similar to that seen in ischemic brain infarcts. Although ED1(+)
      cells decreased by 7-14 days post-stroke, large numbers of Iba1(+) cells
      persisted in the anterior ON. Similar to other CNS ischemic strokes, pure axonal
      ischemia results in the early recruitment of extrinsic macrophages to the
      ischemic region. Manipulation of the inflammatory response may be an important
      variable that could potentially improve visual outcome.

PMID- 19401182
TI  - Neural correlates of cue-unique outcome expectations under differential outcomes
      training: an fMRI study.
AB  - In conditional discriminative choice learning, one learns the relations between
      discriminative/cue stimuli, associated choices, and their outcomes. When each
      correct cue-choice occurrence is followed by a cue-unique trial outcome
      (differential outcomes, DO, procedure), learning is faster and more accurate than
      when all correct cue-choice occurrences are followed by a common outcome (CO
      procedure)--differential outcomes effect (DOE). Superior DO performance is
      theorized to be mediated by the additional learning of cue-unique outcome
      expectations that "enrich" the prospective code available over the delay between
      cue and choice. We anticipated that such learned expectations comprise
      representations of expected outcomes. Here, we conducted an event-related
      functional MR imaging (fMRI) analysis of healthy adults who trained concurrently
      in two difficult but similar perceptual discrimination tasks under DO and CO
      procedures, respectively, and displayed the DOE. Control participants performed
      related tasks that differentially biased them towards delay-period retrospection
      versus prospection. Indeed, when differential outcomes were sensory-perceptual
      events (visual vs. auditory), delay-period expectations were experienced as
      sensory-specific imagery of the respectively expected outcome content, generated
      by sensory-specific cortices. Visual-specific imagery additionally activated
      stimulus-specific representations in prefrontal, lateral and medial frontal,
      fusiform and cerebellar regions, whereas auditory-specific imagery recruited
      claustrum/insula. Posterior parietal cortex (PPC), BA 39, was non-modality
      specific in mediating delay-period cue-unique outcome expectations. Greater
      hippocampal involvement in retrospection than prospection contrasted against the
      PPC's role in prospection. Time course analyses of hippocampal versus PPC
      responses suggest the DOE derives from an earlier transition from retrospection
      to prospection, which taps into long-term associative memory--more enduring.

PMID- 19401183
TI  - S-allyl L-cysteine diminishes cerebral ischemia-induced mitochondrial
      dysfunctions in hippocampus.
AB  - Ischemic brain is highly vulnerable to free radicals mediated secondary neuronal
      damage especially mitochondrial dysfunctions. Present study investigated the
      neuroprotective effect of S-allyl L-cysteine (SAC), a water soluble compound from
      garlic, against cerebral ischemia/reperfusion (I/R)-induced mitochondrial
      dysfunctions in hippocampus (HIP). We used transient rat middle cerebral artery
      occlusion (MCAO) model of brain ischemia. SAC (300 mg/kg) was given twice
      intraperitoneally: 15 min pre-occlusion and 2 h post-occlusion at the time of
      reperfusion. SAC significantly restored ATP content and the activity of
      mitochondrial respiratory complexes in SAC treated group which were severely
      altered in MCAO group. A marked decrease in calcium swelling was observed as a
      result of SAC treatment. Western blot analysis showed a marked decrease in
      cytochrome c release as a result of SAC treatment. The status of mitochondrial
      glutathione (GSH) and glucose 6-phosphate dehydrogenase (G6-PD) was restored by
      SAC treatment with a significant decrease in mitochondrial lipid peroxidation
      (LPO), protein carbonyl (PC) and H2O2 content. SAC significantly improved
      neurological deficits assessed by different scoring methods as compared to MCAO
      group. Also, the brain edema was significantly reduced. The findings of this
      study suggest the ability of SAC in functional preservation of ischemic
      neurovascular units and its therapeutic relevance in the treatment of ischemic
      stroke.

PMID- 19401184
TI  - Obesity alters circadian expressions of molecular clock genes in the brainstem.
AB  - Major components of energy homeostasis, including feeding behavior and glucose
      and lipid metabolism, are subject to circadian rhythms. Recent studies have
      suggested that dysfunctions of molecular clock genes are involved in the
      development of obesity and diabetes. To examine whether metabolic states per se
      alter the circadian clock in the central nervous system (CNS), we analyzed the
      daily mRNA expression profiles of core clock genes in the caudal brainstem
      nucleus of the solitary tract (NTS). In lean C57BL/6 mice, transcript levels of
      the core clock genes (Npas2, Bmal1, Per1, Per2 and Rev-erbalpha) clearly showed
      24-h rhythmicity. On the other hand, the expression profiles of Bmal1 and Rev
      erbalpha were attenuated in mice with high fat diet-induced obesity as well as
      genetically obese KK-A(y) and ob/ob mice. Clock expression levels were increased
      in mice with high fat diet-induced obesity and Cry1 expression levels were
      decreased in KK-A(y) and ob/ob mice. In addition, peroxisome proliferator
      activated receptor alpha (PPARalpha), which reportedly increases the BMAL1
      transcriptional level, was up-regulated in the NTS of these murine models of
      obesity and insulin resistance, suggesting involvement of PPARalpha in the
      attenuation of circadian rhythms in the NTS in obese states. Furthermore, a
      circadian expression profile of a downstream target of clock genes, the large
      conductance Ca(2+)-activated K(+)channel, was disturbed in the NTS of these
      murine obesity models. These perturbations might contribute to neuronal
      dysfunction in obese states. This is the first report showing that obesity
      perturbs the circadian expressions of core clock genes in the CNS.

PMID- 19401186
TI  - Electric light causes cancer? Surely you're joking, Mr. Stevens.
AB  - Night is no longer dark in the modern world, and the Milky Way has disappeared.
      Electric light has benefits but there are also a few detriments. These are (1)
      loss of the night sky, (2) wasted energy, (3) harm to animal and plant life, (4)
      and perhaps increases in some severe human maladies such as cancers of breast and
      prostate. The science on phototransduction for the circadian system and on clock
      gene function is evolving rapidly, and it provides a rationale for the idea that
      circadian disruption from light at night could cause disease. Direct evidence
      from humans and rodent models has also accumulated to the point where the idea is
      no longer fanciful. Although it may seem logical now, the journey on the path
      from electric light to breast cancer has been a tortuous one, at least for me.

PMID- 19401185
TI  - Aberrant functional connectivity in autism: evidence from low-frequency BOLD
      signal fluctuations.
AB  - A number of recent studies have examined functional connectivity in individuals
      with Autism Spectrum Disorders (ASD), generally converging on the finding of
      reduced interregional coordination, or underconnectivity. Underconnectivity has
      been reported between many brain regions and across a range of cognitive tasks,
      and has been proposed to underlie behavioral and cognitive impairments associated
      with ASD. The current study employed functional connectivity MRI (fcMRI) to
      examine interregional correlations of low-frequency BOLD signal fluctuations in
      10 high-functioning participants with ASD and 10 typically developing control
      participants. Whole-brain connectivity with three seed regions of interest (left
      middle frontal, left superior parietal, and left middle occipital cortex) was
      evaluated using fMRI datasets acquired during performance of a source recognition
      task. While fcMRI patterns were found to be largely similar across the two
      groups, including many common areas, effects for the ASD group were generally
      more extensive. These findings, although inconsistent with generalized
      underconnectivity in ASD, are compatible with a model of aberrant connectivity in
      which the nature of connectivity disturbance (i.e., increased or reduced) may
      vary by region. Taking into consideration methodological factors that might
      influence measured fcMRI effects, we suggest that ASD is associated with an
      inefficiency in optimizing network connections to achieve task performance.

PMID- 19401188
TI  - Silencing of Kv4.1 potassium channels inhibits cell proliferation of tumorigenic
      human mammary epithelial cells.
AB  - Potassium channel activity has been shown to facilitate cell proliferation in
      cancer cells. In the present study, the role of Kv4.1 channels in immortal and
      tumorigenic human mammary epithelial cells was investigated. Kv4.1 protein
      expression was positively correlated with tumorigenicity. Moreover, transfection
      with siRNAs targeting Kv4.1 mRNA suppressed proliferation of tumorigenic mammary
      epithelial cells. Experiments using mRNA isolated from human breast cancer
      tissues revealed that the level of Kv4.1 mRNA expression varied depending on the
      stage of the tumor. Kv4.1 protein expression increased during stages T2 and T3
      compared to normal tissue. These results demonstrated that Kv4.1 plays a role in
      proliferation of tumorigenic human mammary epithelial cells. In addition,
      elevated Kv4.1 expression may be useful as a diagnostic marker for staging
      mammary tumors and selective blockers of Kv4.1 may serve to suppress tumor cell
      proliferation.

PMID- 19401187
TI  - Thiol protection in membrane protein purifications: a study with phage holins.
AB  - The lambda holin, or S105, is a small cytoplasmic membrane protein that controls
      the timing of host lysis. Using thiol-specific reagents, we determined that the
      single cysteine residue within S105 was heterogeneously modified during membrane
      extraction and subsequent immobilized metal ion chromatography. Here we describe
      the use of a specific and reversible thiol reagent, 2,2'-dithiodipyridine, to
      generate purified protein with its cysteine residues in the native thiol state.
      The 2,2'-dithiodipyridine protection protocol was also successfully used for
      another unrelated holin, S(21)68, and should be generally useful for the
      purification of membrane proteins.

PMID- 19401189
TI  - Structural basis of the auto-inhibition mechanism of nonreceptor tyrosine kinase
      PTK6.
AB  - Protein tyrosine kinase 6 (PTK6) is composed of SH3, SH2, and Kinase domains,
      with a linker region (Linker) between the SH2 and Kinase domains. Here, we report
      the structural basis of the SH3-Linker interaction that results in auto
      inhibition of PTK6. The solution structures of the SH3 domain and SH3/Linker
      complex were determined by NMR spectroscopy. The structure of the SH3 domain
      forms a conventional beta-barrel with two beta-sheets comprised of five beta
      strands. However, the molecular topology and charge distribution of PTK6-SH3
      slightly differs from that of the other SH3 domains. The structure of the N
      terminal Linker within the complex showed that the proline-rich region (P175
      P187) of the Linker forms a compact hairpin structure through hydrophobic
      interactions. The structure of the SH3/Linker complex revealed intra-molecular
      interaction between the amino acid pairs R22/E190, W44/W184, N65/P177, and
      Y66/P179. Mutations in PTK6 at R22, W44, N65, and Y66 residues in the SH3 domain
      increased catalytic activity compared with wild-type protein, implying that
      specific interactions between hydrophobic residues in the proline-rich linker
      region and hydrophobic residues in the SH3 domain are mainly responsible for down
      regulating the catalytic activity of PTK6.

PMID- 19401190
TI  - The RB/E2F pathway and regulation of RNA processing.
AB  - The retinoblastoma tumor suppressor protein (RB) is inactivated in a majority of
      cancers. RB restricts cell proliferation by inhibiting the E2F family of
      transcription factors. The current model for RB/E2F function describes its role
      in regulating transcription at gene promoters. Whether the RB or E2F proteins
      might play a role in gene expression beyond transcription initiation is not well
      known. This review describes evidence that points to a novel role for the RB/E2F
      network in the regulation of RNA processing, and we propose a model as a
      framework for future research. The elucidation of a novel role of RB in RNA
      processing will have a profound impact on our understanding of the role of this
      tumor suppressor family in cell and developmental biology.

PMID- 19401192
TI  - Mechanism of ribosome assisted protein folding: a new insight into rRNA
      functions.
AB  - The peptidyl transferase center (PTC), present in the domain V of 23S rRNA of
      bacteria can act as a general protein folding modulator. Any general function of
      a nucleic acid polymer (DNA or RNA) is always related to specific
      sequence/sequences. The ribosome mediated protein folding also involves a
      specific interaction between the nucleotides of peptidyl transferase center and
      the amino acids of an unfolded protein. In this article the mechanism of rRNA
      assisted protein folding and its significance in the light of high resolution
      crystal structure of ribosome are discussed.

PMID- 19401191
TI  - T(H)2 cytokines modulate the IL-9R expression on human neutrophils.
AB  - Interleukin (IL)-9 is associated with key pathological features of asthma such as
      airway hyperresponsiveness, bronchoconstriction and mucus production.
      Inflammatory responses mediated by IL-9 rely on the expression of the IL-9R which
      has been reported on lung epithelial cells, T lymphocytes and recently on airway
      granulocyte infiltrates. In this study, we assessed the regulatory and
      constitutive cell surface expression of the IL-9Ralpha in unfractionated and
      purified human neutrophils from atopic asthmatics, atopic non-asthmatics and
      healthy normal controls. We demonstrate that T(H)2 cytokines (IL-4 or IL-13) and
      granulocyte macrophage-colony stimulating factor (GM-CSF) up-regulated mRNA and
      cell surface expression levels of the IL-9Ralpha in primary human and HL-60
      differentiated neutrophils. Pharmacological inhibition of NF-kappaB did not
      affect T(H)2-mediated IL-9Ralpha expression in human neutrophils although IFN
      gamma and IL-10 down-regulated IL-9Ralpha expression when co-incubated with IL-4,
      IL-13 or GM-CSF. Collectively, our results reveal a regulatory function for IFN
      gamma and IL-10 on modulating the inducible IL-9Ralpha expression levels on
      peripheral blood neutrophils by T(H)2 cytokines.

PMID- 19401193
TI  - Up-regulation of protease-activated receptor-1 in diabetic glomerulosclerosis.
AB  - Patients with diabetes are under a hypercoagulable state leading to generation of
      thrombin. It is not known whether thrombin plays a role in the progression of
      diabetic nephropathy. We analyzed gene expression of two thrombin receptors,
      protease-activated receptor-1 (PAR-1) and PAR-4 in the kidney of diabetic db/db
      mice. Mice developed hyperglycemia from 7 to 10 weeks of age and showed renal
      abnormalities such as mesangial expansion and urinary albumin excretion at 10
      weeks of age. PAR-1 mRNA was up-regulated in isolated glomeruli in db/db mice
      compared with age-matched db/m littermates, but PAR-4 mRNA was not. In situ
      hybridization studies showed that PAR-1 mRNA was detected mainly at the
      glomerulus, and that intensive signals were observed in mesangial cells and
      podocytes. The up-regulation of PAR-1 in glomeruli in diabetic mice may play a
      role in the progression of glomerulosclerosis and abnormal urinary albumin
      excretion in diabetic nephropathy.

PMID- 19401194
TI  - The protein content of an adaptor protein, STAP-2 is controlled by E3 ubiquitin
      ligase Cbl.
AB  - Signal transducing adaptor protein-2 (STAP-2) is a recently identified adaptor
      protein that contains pleckstrin and Src homology 2 (SH2)-like domains as well as
      a YXXQ motif in its C-terminal region. Our previous study in T cells demonstrated
      that STAP-2 influences FAK protein levels through recruitment of E3 ubiquitin
      ligase, Cbl, to FAK. In the present study, we found that Cbl directly controls
      the protein levels and activity of STAP-2. STAP-2 physically interacted with Cbl
      through its PH and SH2-like domains. Small-interfering RNA-mediated reduction of
      endogenous Cbl restored STAP-2 protein levels. In contrast, over-expression of
      Cbl induced STAP-2 degradation. Importantly, Cbl-mediated regulation of STAP-2
      protein levels affected Brk/STAP-2-induced STAT3 activation. These results
      indicate that Cbl regulates STAP-2 protein levels and Brk/STAP-2-mediated STAT3
      activation.

PMID- 19401195
TI  - Five different profiles of dihydropyridines in blocking T-type Ca(2+) channel
      subtypes (Ca(v)3.1 (alpha(1G)), Ca(v)3.2 (alpha(1H)), and Ca(v)3.3 (alpha(1I)))
      expressed in Xenopus oocytes.
AB  - 1,4-dihydropyridine (DHP) Ca(2+) antagonists have recently been shown to block T
      type Ca(2+) channels, which may render favorable actions on cardiovascular
      systems. However, this evaluation remains to be done systematically for each T
      type Ca(2+) channel subtype except for the Ca(v)3.1 (alpha(1G)) subtype. To
      address this issue at the molecular level, blocking effects of 14 kinds of DHPs
      (amlodipine, aranidipine, azelnidipine, barnidipine, benidipine, cilnidipine,
      efonidipine, felodipine, manidipine, nicardipine, nifedipine, nilvadipine,
      nimodipine, nitrendipine), which are clinically used for treatments of
      hypertension, on 3 subtypes of T-type Ca(2+) channels [Ca(v)3.2 (alpha(1H)),
      Ca(v)3.3 (alpha(1I)), and Ca(v)3.1 (alpha(1G))] were investigated in the Xenopus
      oocyte expression system using the two-microelectrode voltage-clamp technique.
      These 3 kinds (alpha(1H), alpha(1I) and alpha(1G)) of T-type channels were
      blocked by amlodipine, manidipine and nicardipine. On the other hand,
      azelnidipine, barnidipine, benidipine and efonidipine significantly blocked
      alpha(1H) and alpha(1G), but not alpha(1I) channels, while nilvadipine and
      nimodipine apparently blocked alpha(1H) and alpha(1I), but not alpha(1G)
      channels. Moreover, aranidipine blocked only alpha(1H) channels. By contrast,
      cilnidipine, felodipine, nifedipine and nitrendipine had little effects on these
      subtypes of T-type channels. The result indicates that the blockade of T-type
      Ca(2+) channels by derivatives of DHP Ca(2+) antagonist was selective for the
      channel subtype. Therefore, these selectivities of DHPs in blocking T-type Ca(2+)
      channel subtypes would provide useful pharmacological and clinical information on
      the mode of action of the drugs including side-effects and adverse effects.

PMID- 19401196
TI  - Combined use of propranolol and nifedipine offers better effects on portal vein
      nonuniform remodeling in carbon tetrachloride (CCl(4))-induced portal
      hypertensive rats.
AB  - Portal hypertension is a hemodynamic syndrome due to pathological increase in
      portal flow and portal pressure. These pathological changes in external flow
      loads will inevitably cause vascular remodeling in the portal vein, which is
      usually measured by an opening angle. The present study showed that carbon
      tetrachloride (CCl(4))-induced portal hypertension fully developed at 8 weeks and
      the opening angle of portal vein increased progressively in the pathogenesis of
      intrahepatic portal hypertension which was significantly augmented at 10 weeks.
      Although portal pressure and portal flow were reduced, treatment with either
      propranolol or nifedipine alone for 3 weeks did not decrease the augmented
      opening angle of the portal vein, while combined treatment with propranolol and
      nifedipine markedly reduced the increased opening angle of the portal vein and
      endothelial nitric oxide synthase (eNOS) mRNA expression but not inducible nitric
      oxide synthase (iNOS) mRNA expression. The decreasing effect of propranolol plus
      nifedipine on the elevated opening angle was significantly weakened by L-arginine
      and markedly reinforced by N-nitro-l-arginine-mythel-ester (L-NAME). These
      results indicate that combined use of propranolol and nifedipine ameliorates
      portal vein remodeling in portal hypertension at least by the nitric oxide
      dependent way.

PMID- 19401197
TI  - Berberine-induced decline in circulating CD31+/CD42- microparticles is associated
      with improvement of endothelial function in humans.
AB  - Elevated circulating endothelial microparticles (EMPs) are associated with
      endothelial dysfunction. This study is to investigate whether berberine-induced
      fall in circulating EMPs facilitates improvement of endothelial function in
      healthy subjects. Fourteen healthy subjects received 1-month berberine therapy
      (1.2 g/d) and 11 healthy subjects served as control. Circulating EMPs were
      measured by flow cytometric analysis before and after therapy. Brachial artery
      endothelium-dependent and -independent function was assessed by flow-mediated
      vasodilation (FMD) and sublinqual nitroglyceride-mediated vasodilation (NMD). In
      vitro, human umbilical vein endothelial cells (HUVECs) were stimulated by EMPs
      (10(6)/ml) with or without the presence of berberine (10 microM). Intracellular
      endothelial nitric oxide synthase (eNOS) protein expression was detected by flow
      cytometry. After berberine therapy, circulating CD31(+)/CD42(-) microparticles
      were reduced, which was in parallel with the improvement of flow-mediated
      vasodilation while nitroglyceride-mediated vasodilation kept unchanged. A robust
      relationship was found between drop of circulating CD31(+)/CD42(-) microparticles
      and increased flow-mediated vasodilation. The EMPs in vitro led to diminished
      eNOS protein expression in HUVECs and this EMP-mediated detrimental effect was
      markedly inhibited by berberine. Berberine-induced decline in circulating
      CD31(+)/CD42(-) microparticles contributes to upregulation of endothelial
      function in healthy subjects. Deceasing EMPs may be a novel therapeutic target
      for the improvement of endothelial dysfunction in humans.

PMID- 19401198
TI  - Cryptotanshinone, a lipophilic compound of Salvia miltiorrriza root, inhibits TNF
      alpha-induced expression of adhesion molecules in HUVEC and attenuates rat
      myocardial ischemia/reperfusion injury in vivo.
AB  - The aim of the present study was to evaluate the protective effect of
      cryptotanshinone (CTS), one of active ingredients of Salvia miltiorrhiza root, on
      myocardial ischemia-reperfusion injury in rat due to inhibition of some
      inflammatory events that occur by NF-kappaB-activation during ischemia and
      reperfusion. Myocardial ischemia and reperfusion injury was induced by occluding
      the left anterior descending coronary artery for 30 min followed by either 2 h
      (biochemical analysis) or 24 h (myocardial function and infarct size measurement)
      reperfusion. CTS injected (i.v.) 10 min before ischemia and reperfusion insult.
      CTS significantly reduced the infarct size and improved ischemia and reperfusion
      induced myocardial contractile dysfunction. Furthermore, CTS inhibited NF-kappaB
      translocation, expression of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL
      6), neutrophil infiltration and MPO activity in ischemic myocardial tissues. CTS
      also significantly reduced plasma levels of TNF-alpha, IL-1beta due to ischemia
      and reperfusion. Interestingly, H(2)O(2)-stimulated NF-kappaB-luciferase activity
      and TNF-alpha-induced expression of vascular cell adhesion molecule-1 (VCAM-1)
      and intracellular adhesion molecule-1 (ICAM-1) expressions in human umbilical
      vein endothelial cells (HUVEC) were significantly inhibited by CTS. Taken
      together, it is concluded that CTS may attenuate ischemia and reperfusion-induced
      microcirculatory disturbances by inhibition of proinflammatory cytokine
      production, reduction of neutrophil infiltration and possibly inhibition of
      adhesion molecules through inhibition of NF-kappaB-activation during ischemia and
      reperfusion.

PMID- 19401200
TI  - Structures of the tumor necrosis factor alpha inducing protein Tipalpha: a novel
      virulence factor from Helicobacter pylori.
AB  - Helicobacter pylori secretes a unique virulence factor, Tipalpha, that enters
      gastric cells and both stimulates the production of the TNF-alpha and activates
      the NF-kappaB pathway. The structures of a truncated version of Tipalpha
      (TipalphaN34) in two crystal forms are presented here. Tipalpha adopts a novel
      beta(1)alpha(1)alpha(2)beta(2)beta(3)alpha(3)alpha(4) topology that can be
      described as a combination of three domains. A first region consists in a short
      flexible extension, a second displays a dodecin-like fold and a third is a
      helical bundle domain similar to the sterile alpha motif (SAM). Analysis of the
      oligomerisation states of TipalphaN34 in the crystals and in solution suggests
      that the disulfide bridges could hold together Tipalpha monomers during their
      secretion in the gastric environment.

PMID- 19401199
TI  - Absence of SPARC leads to impaired lens circulation.
AB  - SPARC is a matricellular glycoprotein involved in regulation of extracellular
      matrix, growth factors, adhesion, and migration. SPARC-null mice have altered
      basement membranes and develop posterior sub-capsular cataracts with cell
      swelling and equatorial vacuoles. Exchange of fluid, nutrients, and waste
      products in the avascular lens is driven by a unique circulating ion current. In
      the absence of SPARC, increased circulation of fluid, ions, and small molecules
      led to increased fluorescein distribution in vivo, loss of resting membrane
      polarization, and altered distribution of small molecules. Microarray analysis of
      SPARC-null lenses showed changes in gene expression of ion channels and
      receptors, matrix and adhesion genes, cytoskeleton, immune response genes, and
      cell signaling molecules. Our results confirm the hypothesis that the regulation
      of SPARC on cell-capsular matrix interactions can increase the circulation of
      fluid and ions in the lens, and the phenotype in the SPARC-null mouse lens is the
      result of multiple intersecting functional pathways.

PMID- 19401201
TI  - Mapping of sex hormone receptors and their modulators along the nephron of male
      and female mice.
AB  - Renal functions are regulated by steroid sex hormones, but the exhaustive
      identification of their receptors along the nephron is still lacking. Here, we
      have localized all known nuclear or membrane-bound sex hormone receptors and some
      of their activators along the nephron of male and female mice. Almost all
      receptors are present in male and female kidney, some of them having very
      restricted localization. Only one gene tested among 11 (ARA54) exhibits a gender
      difference in the level of its expression. This first "renal map" of sex steroid
      receptor expression may serve as a pre-requisite for investigating the role of
      these hormones on kidney functions.

PMID- 19401202
TI  - Effects of cortisol, growth hormone and prolactin on gill claudin expression in
      Atlantic salmon.
AB  - We recently showed that a series of tight junction proteins of the claudin family
      are regulated in the gill of salmon during salinity acclimation. The aim of the
      present study was to investigate the role of cortisol, growth hormone (GH) and
      prolactin (PRL) on regulation of expression of these isoforms. Experiments on
      primary cultures of gill tissue showed that cortisol stimulates claudin 10e, 27a
      and 30 mRNA levels while no significant effects were observed on claudin 28a and
      28b. The associated receptor signalling pathway was examined using glucocorticoid
      and mineralocorticoid receptor antagonists RU486 and spironolactone,
      respectively. The observed in vitro responses were blocked by RU486, suggesting
      the involvement of a glucocorticoid type receptor. Injections of FW salmon with
      cortisol increased the expression of claudin 10e, 27a, and 30 but did not affect
      claudin 28a and 28b significantly. While GH had no effect on its own, the
      combination of GH and cortisol reduced claudin 28b levels. Injection of SW salmon
      with PRL selectively increased the expression of claudin 28a but had no effect on
      the other examined isoforms. The data shows that FW- (27a and 30) and SW-induced
      (10e) claudins are all stimulated by cortisol while the major osmoregulatory
      hormones GH and PRL had no effect on these salinity sensitive isoforms. This
      suggests that other hormones and/or osmotic conditions interact with cortisol to
      determine claudin composition in the gill.

PMID- 19401204
TI  - New evidences for the involvement of 20beta-hydroxysteroid dehydrogenase in final
      oocyte maturation of air-breathing catfish.
AB  - 20beta-hydroxysteroid dehydrogenase (20beta-HSD) synthesizes 17alpha,20beta
      dihdroxy-4-pregnen-3-one, the steroid required for resumption of prophase-I
      arrested oocytes in teleosts. Though 20beta-HSD cDNAs have been cloned from few
      fish species, its role in final oocyte maturation (FOM) is still questionable. To
      study the role of 20beta-HSD in FOM more explicitly, we cloned and characterized
      20beta-HSD from ovary of air-breathing catfish, Clarias gariepinus.
      Interestingly, Escherichia coli expressed recombinant proteins, both full-length
      and an N-terminal truncated proteins catalyzed the reduction of steroids and
      xenobiotics, however there was significant difference between them. Semi
      quantitative RT-PCR and Western blots demonstrated the presence of 20beta-HSD
      transcript and protein in various tissues with relatively higher level in gonads,
      gill, kidney and brain. A positive correlation of 20beta-HSD expression was
      observed in different phases of ovarian cycles.
      Immunocytochemical/immunofluoroscence analysis with specific antibody identified
      presence of 20beta-HSD in follicular layer of ovary. Real-time RT-PCR and Western
      blotting showed an induction of 20beta-HSD expression during human chorionic
      gonadotropin (hCG)-induced oocyte maturation, in vitro and in vivo.
      Concomitantly, a rise in 20beta-HSD enzyme activity was also noticed. Specific
      inhibitors of carbonyl reductase inhibited not only recombinant protein catalytic
      activity but also hCG-induced oocyte maturation in a dose-dependent manner as
      evidenced by blocking of germinal vesicle break down. These results together
      provide new evidences for the involvement of 20beta-HSD in the FOM/meiotic
      maturation.

PMID- 19401203
TI  - Gene-expression signatures of Atlantic salmon's plastic life cycle.
AB  - How genomic expression differs as a function of life history variation is largely
      unknown. Atlantic salmon exhibits extreme alternative life histories. We defined
      the gene-expression signatures of wild-caught salmon at two different life stages
      by comparing the brain expression profiles of mature sneaker males and immature
      males, and early migrants and late migrants. In addition to life-stage-specific
      signatures, we discovered a surprisingly large gene set that was differentially
      regulated-at similar magnitudes, yet in opposite direction-in both life history
      transitions. We suggest that this co-variation is not a consequence of many
      independent cellular and molecular switches in the same direction but rather
      represents the molecular equivalent of a physiological shift orchestrated by one
      or very few master regulators.

PMID- 19401206
TI  - In vitro development of a hemangioblast from a human embryonic stem cell,
      SNUhES#3.
AB  - AIMS: Recent reports demonstrated that a hemangioblast population emerged during
      hematopoietic development in both mouse and human embryonic stem cell (hESC)
      differentiation cultures. MAIN METHODS: In this study, a new uncharacterized hESC
      line, SNUhES#3, was studied for its capacity to proliferate with STO cells and
      differentiate into hemangioblasts in co-culture with OP9 cells. KEY FINDINGS: We
      were able to obtain CD34(+)CD45(-) cells from SNUhES#3 cells after 12 days of in
      vitro culture, and this cell population could be maximized to 12.6% of the total.
      These cells, derived from SNUhES#3, showed the morphology of hematopoietic
      precursor cells and endothelial lineage cells with high efficiency. Reverse
      transcription polymerase chain reaction (RT-PCR) analysis showed that the
      hematopoietic markers CD34, GATA2, and LMO2 were co-expressed with the
      endothelial marker CD31 from day 8, whereas ES cell marker OCT4 no longer existed
      at an early stage. Moreover, we found that the efficacy of colony forming by
      SNUhES#3 cells is better than that of H9 cells. SIGNIFICANCE: These findings
      provide evidence that SNUhES#3 cells can be used as an established human ESC
      line, and co-culture with OP9 can induce SNUhES#3 cells to differentiate into
      hemangioblasts, the common precursors of the hematopoietic and endothelial
      lineages.

PMID- 19401205
TI  - Functional genomics of hsp-90 in parasitic and free-living nematodes.
AB  - Heat shock protein 90 (Hsp-90) is a highly conserved essential protein in
      eukaryotes. Here we describe the molecular characterisation of hsp-90 from three
      nematodes, the free-living Caenorhabditis elegans (Ce) and the parasitic worms
      Brugia pahangi (Bp) and Haemonchus contortus (Hc). These molecules were
      functionally characterised by rescue of a Ce-daf-21 (hsp-90) null mutant. Our
      results show a gradient of rescue: the C. elegans endogenous gene provided full
      rescue of the daf-21 mutant, while Hc-hsp-90 provided partial rescue. In
      contrast, no rescue could be obtained using a variety of Bp-hsp-90 constructs,
      despite the fact that Bp-hsp-90 was transcribed and translated in the mutant
      worms. daf-21 RNA interference (RNAi) experiments were carried out to determine
      whether knock-down of the endogenous daf-21 mRNA in N2 worms could be
      complemented by expression of either parasite gene. However neither parasite gene
      could rescue the daf-21 (RNAi) phenotypes. These results indicate that factors
      other than the level of sequence identity are important for determining whether
      parasite genes can functionally complement in C. elegans.

PMID- 19401207
TI  - Importance of phase alignment for interocular suppression.
AB  - We measured contrast thresholds for Gabor targets in the presence of maskers
      which had higher or lower spatial frequencies than the targets. A high-pass
      fractal masker elevated target contrast thresholds at low and intermediate
      pedestal contrasts in both monocular and dichoptic modes of presentation,
      suggesting that the masking occurs after a monocular processing stage. Moreover
      we found that a high-pass checkerboard masker elevated thresholds at the low and
      intermediate pedestal contrasts and that most of this threshold elevation
      disappeared when the phase of the masker's spatial components were scrambled.
      This masking was effective only in the dichoptic presentation, not in the
      monocular presentation. These results indicate that phase alignment of the high
      spatial frequency components plays a crucial role for interocular suppression. We
      speculate that phase alignments signal the existence of a luminance contour in
      the monocular image and that this signal suppresses processing of information in
      the other eye when there is no corresponding signal in that eye.

PMID- 19401210
TI  - Studying the effectiveness of penetration enhancers to deliver retinol through
      the stratum cornum by in vivo confocal Raman spectroscopy.
AB  - The purpose of this study is to monitor in vivo the effect of chemical
      penetration enhancers on the delivery of trans-retinol into human skin. Chemical
      penetration enhancers reversibly alter barrier properties of the SC by disruption
      of the membrane structures or maximising drug solubility with the skin. So far,
      most of permeation or penetration experiments are performed in vitro. Raman
      spectroscopy is uniquely placed to be able to measure biological processes in
      vivo and this paper shows for the first time that the effect of penetration
      enhancer on the delivery of trans-retinol can successfully be measured in vivo
      using this technique. Here, the volar forearm of volunteers was treated with four
      formulations. One formulation is a highly effective model delivery system
      identified from ex vivo experiments: trans-retinol in Propylene Glycol
      (PG)/ethanol, with PG being a well-known and efficient penetration enhancer. The
      other three formulations are based on 0.3% trans-retinol in Caprylic/Capric Acid
      Triglyceride (MYRITOL 318), an oil commonly used in skin creams but in two of
      them a specific penetration enhancer is added. One contains a lipid extractor,
      Triton X 100, whereas another formulation contains a lipid fluidiser, Oleic Acid.
      Solutions were applied once and measurements were performed up to 6 h after
      treatment. Remarkable differences in the delivery of trans-retinol between
      formulation with or without penetration enhancer can clearly be seen. Moreover,
      the type of penetration enhancer is also shown to influence the delivery. While
      using the Oleic Acid, which is a lipid fluidiser, a better delivery of trans
      retinol in the skin can be detected. For the first time, the effect of
      penetration enhancer on the delivery of trans-retinol has been monitored, non
      invasively in vivo, with time.

PMID- 19401211
TI  - Targeting the G-quadruplex-forming region near the P1 promoter in the human BCL-2
      gene with the cationic porphyrin TMPyP4 and with the complementary C-rich strand.
AB  - The B-cell lymphoma-2 (bcl-2) gene contains a region that has been implicated in
      the regulation of bcl-2 gene expression. This region can form G-quadruplex
      structures in solution [J.X. Dai, T.S. Dexheimer, D. Chen, M. Carver, A. Ambrus,
      R.A. Jones, D.Z. Yang, An intramolecular G-quadruplex structure with mixed
      parallel/antiparallel G-strands formed in the human BCL-2 promoter region in
      solution, J. Am. Chem. Soc. 128 (2006) 1096-1098.]. Here, we examined the acid
      base and conformational equilibria of this G-quadruplex-forming region (BCL2G),
      as well as its interaction with both the porphyrin TMPyP4 and with the
      complementary C-rich strand. We used molecular absorption and circular dichroism
      techniques, in tandem with multivariate analysis tools. The results revealed the
      formation of an interaction complex BCL2G:TMPyP4 with a stoichiometry of 1:2 and
      an equilibrium constant equal to 5.0 (+/-2.3) x 10(13) M(-2). Addition of the
      complementary C-rich strand to BCL2G induces the predominant formation of the
      Watson-Crick double-helix with an equilibrium constant equal to 10(7.7) M(-1) (at
      pH 7.1). Finally, the pH-induced formation of quadruplex structures from the
      Watson-Crick double-helix is characterized.

PMID- 19401212
TI  - Mapping of 5' and 3'-ends of sunflower mitochondrial nad6 mRNAs reveals a very
      complex transcription pattern which includes primary transcripts lacking 5'-UTR.
AB  - Nad6 orf, encoded in the sunflower mitochondrial genome in single copy contains a
      non-conserved 3'-extension. The transcription of the nad6 locus generates a
      highly complex pattern. Three main transcripts of 1240, 960 and 870 nt have been
      characterized by different approaches. The two smaller ones are apparently the
      most abundant of the steady-state RNA population and are generated as primary
      transcription products as well as by processing of the 1240 nt transcript. Their
      5'-UTRs are absent or very short. Whereas the 3'-ends of the 960 nt transcripts
      contain a TGA codon the shorter one terminates at positions excluding the stop
      codon. The fate of transcripts to promote the synthesis of NAD6 sunflower protein
      seems, thus, to rely on the occurrence of mechanisms yet to be identified.

PMID- 19401208
TI  - Who's in charge? Nuclear receptor coactivator and corepressor function in brain
      and behavior.
AB  - Steroid hormones act in brain and throughout the body to regulate a variety of
      functions, including development, reproduction, stress and behavior. Many of
      these effects of steroid hormones are mediated by their respective receptors,
      which are members of the steroid/nuclear receptor superfamily of transcriptional
      activators. A variety of studies in cell lines reveal that nuclear receptor
      coregulators are critical in modulating steroid receptor-dependent transcription.
      Thus, in addition to the availability of the hormone and the expression of its
      receptor, nuclear receptor coregulators are essential for efficient steroid
      dependent transactivation of genes. This review will highlight the importance of
      nuclear receptor coregulators in modulating steroid-dependent gene expression in
      brain and the regulation of behavior.

PMID- 19401213
TI  - Identification by high throughput screening of small compounds inhibiting the
      nucleic acid destabilization activity of the HIV-1 nucleocapsid protein.
AB  - Due to its highly conserved zinc fingers and its nucleic acid chaperone
      properties which are critical for HIV-1 replication, the nucleocapsid protein
      (NC) constitutes a major target in AIDS therapy. Different families of molecules
      targeting NC zinc fingers and/or inhibiting the binding of NC with its target
      nucleic acids have been developed. However, their limited specificity and their
      cellular toxicity prompted us to develop a screening assay to target molecules
      able to inhibit NC chaperone properties, and more specifically the initial NC
      promoted destabilization of the nucleic acid secondary structure. Since this
      destabilization is critically dependent on the properly folded fingers, the
      developed assay is thought to be highly specific. The assay was based on the use
      of cTAR DNA, a stem-loop sequence complementary to the transactivation response
      element, doubly labelled at its 5' and 3' ends by a rhodamine 6G fluorophore and
      a fluorescence quencher, respectively. Addition of NC(12-55), a peptide
      corresponding to the zinc finger domain of NC, to this doubly-labelled cTAR, led
      to a partial melting of the cTAR stem, which increases the distance between the
      two labels and thus, restores the rhodamine 6G fluorescence. Thus, positive hits
      were detected through the decrease of rhodamine 6G fluorescence. An "in-house"
      chemical library of 4800 molecules was screened and five compounds with IC(50)
      values in the micromolar range have been selected. The hits were shown by mass
      spectrometry and fluorescence anisotropy titration to prevent binding of NC(12
      55) to cTAR through direct interaction with the NC folded fingers, but without
      promoting zinc ejection. These non-zinc ejecting NC binders are a new series of
      anti-NC molecules that could be used to rationally design molecules with
      potential anti-viral activities.

PMID- 19401209
TI  - Neuroprotective effects of estrogens following ischemic stroke.
AB  - Our laboratory has investigated whether and how 17beta-estradiol (E(2)) protects
      the brain against neurodegeneration associated with cerebrovascular stroke. We
      have discovered that low, physiological concentrations of E(2), which are
      strikingly similar to low-basal circulating levels found in cycling mice,
      dramatically protect the brain against stroke injury, and consequently revealed
      multiple signaling pathways and key genes that mediate protective action of E(2).
      Here we will review the discoveries comprising our current understanding of
      neuroprotective actions of estrogens against ischemic stroke. These findings may
      carry far reaching implications for improving the quality of life in aging
      populations.

PMID- 19401214
TI  - Green fluorescent protein - Tagged HCV non-enveloped capsid like particles:
      development of a new tool for tracking HCV core uptake.
AB  - Circulating 'free' non-enveloped Hepatitis C virus (HCV) core protein has been
      demonstrated in HCV-infected patients, and HCV subgenomes with deletions of the
      envelope proteins have been previously identified. Initial studies from our
      laboratory, previously published, indicated that expression of HCV core in insect
      cells can direct the formation of capsid-like particles lacking the envelope
      glycoproteins. These protein nanospheres, morphologically similar to natural
      capsids, were shown to be taken up by human hepatic cells and to produce cell
      signalling events. To follow the intracellular fate of these particles we fused
      the core protein to eGFP. We demonstrate that the chimeric proteins core(173)
      eGFP, eGFP-core(191) and eGFP-core(173) can be efficiently expressed, self
      assembled, and form fluorescent non-enveloped capsid-like particles. By using
      confocal microscopy and FACS analysis, we provide evidence that the fluorescent
      nanospheres can not only enter human hepatic cells - the main target of HCV - but
      also human immune cells such as T and B lymphocytes, as well as human myeloid
      leukaemia cells differentiated along the monocyte/macrophage-like pathway. The
      fluorescent particles might thus be used to trace the intracellular trafficking
      of naked HCV capsids as showed by live microscopy and to further understand their
      biological significance.

PMID- 19401216
TI  - Deep brain stimulation of the posterior hypothalamic nucleus reverses akinesia in
      bilaterally 6-hydroxydopamine-lesioned rats.
AB  - Deep brain stimulation (DBS) of the basal ganglia motor circuitry is a highly
      effective treatment for the debilitating motor symptoms of Parkinson's disease
      (PD). However, recent findings have indicated promising potential for PD therapy
      with DBS in brain structures outside the basal ganglia. For example, high
      frequency stimulation of the posterior hypothalamic nucleus (PH) can reverse
      haloperidol-induced akinesia in rats [Jackson J, Young CK, Hu B, Bland BH (2008)
      High frequency stimulation of the posterior hypothalamic nucleus restores
      movement and reinstates hippocampal-striatal theta coherence following
      haloperidol-induced catalepsy. Exp Neurol 213:210-219]. In the current study, we
      used the bilateral 6-hydroxydopamine lesion model of Parkinsonian akinesia in
      male Long-Evans rats to further explore the efficacy of PH DBS. The application
      of PH DBS in lesioned animals reversed akinesia in an active avoidance paradigm
      with increased latency compared to pre-lesion performance. The dramatic reversal
      of akinesia in two models of rodent Parkinsonism by PH DBS warrants further
      exploration of its therapeutic potential.

PMID- 19401215
TI  - Parathyroid hormone 2 receptor and its endogenous ligand tuberoinfundibular
      peptide of 39 residues are concentrated in endocrine, viscerosensory and auditory
      brain regions in macaque and human.
AB  - Parathyroid hormone receptor 2 (PTH2R) and its ligand, tuberoinfundibular peptide
      of 39 residues (TIP39) constitute a neuromodulator system implicated in endocrine
      and nociceptive regulation. We now describe the presence and distribution of the
      PTH2R and TIP39 in the brain of primates using a range of tissues and ages from
      macaque and human brain. In situ hybridization histochemistry of TIP39 mRNA,
      studied in young macaque brain, due to its possible decline beyond late postnatal
      ages, was present only in the thalamic subparafascicular area and the pontine
      medial paralemniscal nucleus. In contrast, in situ hybridization histochemistry
      in macaque identified high levels of PTH2R expression in the central amygdaloid
      nucleus, medial preoptic area, hypothalamic paraventricular and periventricular
      nuclei, medial geniculate, and the pontine tegmentum. PTH2R mRNA was also
      detected in several human brain areas by RT-PCR. The distribution of PTH2R
      immunoreactive fibers in human, determined by immunocytochemistry, was similar to
      that in rodents, including dense fiber networks in the medial preoptic area,
      hypothalamic paraventricular, periventricular and infundibular (arcuate) nuclei,
      lateral hypothalamic area, median eminence, thalamic paraventricular nucleus,
      periaqueductal gray, lateral parabrachial nucleus, nucleus of the solitary tract,
      sensory trigeminal nuclei, medullary dorsal reticular nucleus, and dorsal horn of
      the spinal cord. Co-localization suggested that PTH2R fibers are glutamatergic,
      and that TIP39 may directly influence hypophysiotropic somatostatin containing
      and indirectly influence corticotropin releasing-hormone containing neurons. The
      results demonstrate that TIP39 and the PTH2R are expressed in the brain of
      primates in locations that suggest involvement in regulation of fear, anxiety,
      reproductive behaviors, release of pituitary hormones, and nociception.

PMID- 19401217
TI  - A role for dopamine D2 receptors in reversal learning.
AB  - Reversal learning has been shown to require intact serotonergic innervation of
      the forebrain neocortex. Whether dopamine acting through D2 receptors plays a
      complementary role in this anatomic area is still unclear. Here we show that mice
      lacking dopamine D2 receptors exhibited significantly impaired performance in the
      reversal learning phase of an attention-set-shifting task (ASST) and that wild
      type mice treated chronically with the D2-like receptor antagonist haloperidol
      exhibited the same cognitive deficit. The test-phase-specific deficits of D2
      mutants and haloperidol-treated mice were also accompanied by deficits in the
      induction of expression of early growth response gene 2 (egr-2), a regulatory
      transcription factor previously shown to be selectively induced in the
      ventrolateral orbital frontal cortex and the pre- and infralimbic medial
      prefrontal cortex of ASST-tested mice. D2-receptor knockout mice and haloperidol
      treated wild type, however, exhibited lower egr-2 expression in these anatomic
      regions after completion of an ASST-test phase that required reversal learning
      but not after completion of set-shifting phases without rule reversals. In
      contrast, mice treated chronically with clozapine, an atypical neuroleptic drug
      with lower D2-receptor affinity and broader pharmacological effects, had deficits
      in compound discrimination phases of the ASST, but also these deficits were
      accompanied by lower egr-2 expression in the same anatomic subregions. Thus, the
      findings indicate that egr-2 expression is a sensitive indicator of test-phase
      specific performance in the ASST and that normal function of D2 receptors in
      subregions of the orbital frontal and the medial prefrontal cortex is required
      for cognitive flexibility in tests involving rule reversals.

PMID- 19401218
TI  - Amyloid beta-protein stimulates trafficking of cholesterol and caveolin-1 from
      the plasma membrane to the Golgi complex in mouse primary astrocytes.
AB  - The Golgi complex plays a key role in cholesterol trafficking in cells. Our
      earlier study demonstrated amyloid beta-protein (Abeta) alters cholesterol
      distribution and abundance in the Golgi complex of astrocytes. We now test the
      hypothesis that the Abeta-induced increase in Golgi complex cholesterol is due to
      retrograde movement of the cholesterol carrier protein caveolin-1 from the cell
      plasma membrane to the Golgi complex in astrocytes. Results with mouse primary
      astrocytes indicated that Abeta(1-42)-induced increase in cholesterol and
      caveolin abundance in the Golgi complex was accompanied by a reduction in
      cholesterol and caveolin levels in the plasma membrane. Transfected rat
      astrocytes (DITNC1) with siRNA directed at caveolin-1 mRNA inhibited the Abeta(1
      42)-induced redistribution of both cholesterol and caveolin from the plasma
      membrane to the Golgi complex. In astrocytes not treated with Abeta(1-42),
      suppression of caveolin-1 expression also significantly reduced cholesterol
      abundance in the Golgi complex, further demonstrating the role for caveolin in
      retrograde transport of cholesterol from the plasma membrane to the Golgi
      complex. Perturbation of this process by Abeta(1-42) could have consequences on
      membrane structure and cellular functions requiring optimal levels of
      cholesterol.

PMID- 19401219
TI  - Chronic stress effects on dendritic morphology in medial prefrontal cortex: sex
      differences and estrogen dependence.
AB  - A growing body of work has documented sex differences in many behavioral,
      neurochemical, and morphological responses to stress. Chronic stress alters
      morphology of dendrites in medial prefrontal cortex in male rats. However,
      potential sex differences in stress-induced morphological changes in medial
      prefrontal cortex have not been examined. Thus, in Experiment 1 we assessed
      dendritic morphology in medial prefrontal cortex in male and female rats after
      chronic stress. Male and female rats underwent either 3 hours of restraint daily
      for 1 week or were left unhandled except for weighing. On the final day of
      restraint, all rats were euthanized and brains were stained using a Golgi-Cox
      procedure. Pyramidal neurons in layer II-III of medial prefrontal cortex were
      drawn in three dimensions, and morphology of apical and basilar arbors was
      quantified. In males, stress decreased apical dendritic branch number and length,
      whereas in females, stress increased apical dendritic length. In Experiment 2, we
      assessed whether estradiol mediates this stress-induced dendritic hypertrophy in
      females by assessing the effects of restraint stress on female rats that had
      received either ovariectomy with or without 17-beta-estradiol replacement or sham
      ovariectomy. Brains were processed and neurons reconstructed as described in
      Experiment 1. Both sham-operated and ovariectomized rats with estradiol implants
      showed stress-induced increases in apical dendritic material, whereas ovariectomy
      without estradiol replacement prevented the stress-induced increase. Thus, the
      stress-induced increase in apical dendritic material in females is estradiol
      dependent.

PMID- 19401221
TI  - Over-representation of species-specific vocalizations in the awake mouse inferior
      colliculus.
AB  - Social vocalizations are particularly important stimuli in an animal's auditory
      environment. Because of their importance, vocalizations should be strongly
      represented in auditory pathways. Mice commonly emit ultrasonic vocalizations
      with spectral content between 45 and 100 kHz. However, there is limited
      representation of these ultra-high frequencies (particularly those greater than
      60 kHz) throughout the ascending auditory system. Here, we show that neurons in
      the inferior colliculus (IC) of mice respond strongly to conspecific
      vocalizations even though the energy in the vocalizations is above the neurons'
      frequency tuning curves. This results in an over-representation of species
      specific vocalizations in the IC. In addition, neurons in mouse IC show
      selectivity among different vocalizations. Many vocalization-responsive neurons
      do not respond to the individual ultrasonic frequencies contained within the
      vocalizations, but they do respond to combinations of ultrasonic tones if the
      difference between the tones is within the excitatory frequency tuning curve. The
      combinations of tones that elicit responses are the quadratic and/or cubic
      intermodulation distortion components that are generated by the cochlea. Thus,
      the intermodulation distortions in the cochlea may provide a previously
      overlooked mechanism for auditory processing of complex stimuli such as
      vocalizations. The implication of these findings is that nonlinear interactions
      of frequencies, possibly caused by distortions in the system, may be used to
      enhance the sensitivity to behaviorally important stimuli.

PMID- 19401220
TI  - Neuroglobin-overexpression alters hypoxic response gene expression in primary
      neuron culture following oxygen glucose deprivation.
AB  - Neuroglobin (Ngb) is a tissue globin specifically expressed in neurons. Our
      laboratory and others have shown that Ngb overexpression protects neurons against
      hypoxia/ischemia, but the underlying mechanisms remain poorly understood. Recent
      studies demonstrate that hypoxia/ischemia induces a multitude of spatially and
      temporally regulated responses in gene expression, and initial evidence suggested
      that Ngb might function in altering biological processes of gene expression. In
      this study, we asked how Ngb may help regulate genes responsive to hypoxia.
      Expression of hypoxic response genes following oxygen-glucose deprivation (OGD)
      was examined using mRNA arrays in neuroglobin-overexpressing transgenic (Ngb-Tg)
      and wild type (WT) mouse neurons. From a total of 113 genes on the microarray,
      mRNA expression of 65 genes was detected. Under rest condition, 14 genes were
      downregulated in Ngb-Tg neurons compared to WT. In WT neurons, after 4-h OGD
      followed by 4-h reoxygenation (O4/R4), 20 genes were significantly downregulated,
      and only Fos mRNA was significantly increased. However, out of the 20
      downregulated genes in WT neurons, 12 of them were no longer significantly
      changed in Ngb-Tg neurons: Add1, Arnt2, Camk2g, Cstb, Dr1, Epas1, Gna11, Hif1a,
      Il6st, Khsrp, Mars and Rara. Among these 12 genes, 8 (Add1, Camk2g, Cstb, Dr1,
      Epas1, Gna11, Hif1a, Khsrp) were already reduced in Ngb-Tg neurons compared to WT
      under rest conditions. Additionally, three genes that initially showed no changes
      in WT neurons (Ctgf, Egfr and Pea15) were downregulated after OGD in the Ngb-Tg
      neurons. These findings suggest that Ngb overexpression modulates mRNA expression
      of multiple hypoxic response genes in the early phase after OGD/reoxygenation.
      Further studies on these gene networks and interactions may lead to better
      understanding of Ngb in signaling pathways that contribute to neuroprotection.

PMID- 19401222
TI  - Olfactory bulb ventricles as a frequent finding in magnetic resonance imaging
      studies of the olfactory system.
AB  - Background. In some species an embryologic cavity inside the olfactory bulb (OB)
      persists and is called olfactory bulb ventricle (OBV). It is generally assumed
      that OBVs in humans are solitary findings representing remnants of embryologic
      structures that were not fully regressed, although the incidence of OBVs was
      never examined. Using magnetic resonance imaging (MRI), the present study aimed
      to study the incidence of OBVs in healthy human subjects. Material and methods. A
      total of 122 individuals participated. Volumes of the right and left OB were
      determined using MRI scans and a standardized protocol for OB analysis. For
      comparison, OBs of 42 cadavers were collected and sectioned. Results. The main
      finding of this study was the high incidence of OBV-like structures in our study
      group. Seventy-two out of 122 (59%) participants yielded signs for an OBV whereas
      three out of 42 postmortem OBs contained histologically detectable OBV.
      DISCUSSION: This stands in disagreement with the previous assumption of complete
      obliteration at the time of birth. This discrepancy may be explained by the fact
      that our present findings are based on modern MRI techniques with much higher
      resolution than 10 or 20 years ago. Another possible explanation for the
      discrepancy between studies based on MRI and histopathology might relate to
      postmortem resorption of cerebrospinal fluid from OBVs. Especially with a long
      postmortem interval OBVs may collapse and may no longer appear as an open cavity.

PMID- 19401223
TI  - Effects of intranasally applied dopamine on behavioral asymmetries in rats with
      unilateral 6-hydroxydopamine lesions of the nigro-striatal tract.
AB  - Due to its lipophobic properties, dopamine is unable to cross the blood-brain
      barrier following systemic application. However, recently it has been
      demonstrated that, when applied directly via the nasal passages in the rat,
      dopamine exerts neurochemical and behavioural action, including increases of
      dopamine in striatal subregions, antidepressive-like action, and increased
      behavioral activity. These effects could potentially be mediated by exogenous
      dopamine acting as a direct agonist at postsynaptic dopamine receptors. However,
      it is also possible that intranasally applied dopamine acts indirectly via the
      modulation of the activity of dopaminergic cell bodies. To approach this
      question, the present study used rats with unilateral 6-hydroxydopamine (6-OHDA)
      lesions of the nigrostriatal tract, as these lesions lead to pharmacologically
      stimulated behavioural asymmetries which are specific for direct and indirect
      dopamine agonists. We found that 7 days of repeated treatment with intranasal
      dopamine induced a sensitization of the turning response to amphetamine, but not
      to apomorphine. Furthermore, intranasal dopamine dose-dependently increased the
      use of the forepaw ipsilateral to the 6-OHDA-lesioned side of the brain. These
      results suggest that intranasally administered dopamine acts via an indirect
      mechanism of action, putatively by increasing the release of endogenous dopamine
      in the brain.

PMID- 19401224
TI  - Olfactory-induced brain activity in Parkinson's disease relates to the expression
      of event-related potentials: a functional magnetic resonance imaging study.
AB  - Olfactory disorders are common in patients with idiopathic Parkinson's disease
      (IPD). In IPD patients with hyposmia olfactory event-related potentials (ERPs)
      are typically found to be delayed or absent. Altered ERPs in IPD patients may
      also be consistent with reduced neuronal activity in the medial temporal lobe
      following olfactory stimulation, as demonstrated by functional magnetic resonance
      imaging (fMRI). We analyzed ERPs and fMRI scans of hyposmic IPD patients (n=18)
      to gain further insight about the brain regions involved in generation of
      olfactory ERPs. Patients were separated into two groups (n=9 per group), based on
      the detectability (+) or non-detectability (-) of ERPs. Central activation during
      olfactory stimulation was examined using fMRI. Both ERP+ and ERP- patients showed
      activity in brain areas relevant to olfactory processing, such as the amygdala,
      parahippocampal regions, and temporal regions (BA 37, 21/22). Comparison of both
      groups revealed higher activation in ERP+ patients, especially in the amygdala,
      parahippocampal cortex, inferior frontal gyrus (BA 47), insula, cingulate gyrus,
      striatum, and inferior temporal gyrus. The relationship between the expression of
      olfactory ERPs and cortical activation patterns seen during olfactory stimulation
      in fMRI in IPD patients supports the idea that ERPs are a sensitive marker of
      neurodegeneration in olfactory regions. In accordance with current
      neuropathological staging concepts, olfactory ERPs may be reflecting pathological
      changes in olfactory regions, independent of the typically observed nigro
      striatal degeneration in IPD. Reduced activation of primary olfactory areas in
      the ERP-group may reflect a severe disruption of olfactory processing in these
      patients.

PMID- 19401226
TI  - Effect of prolonged contralateral acoustic stimulation on transient evoked
      otoacoustic emissions.
AB  - Although the suppressive effect of the medial olivocochlear system (MOCS) on
      peripheral auditory active mechanisms is well documented in humans, the effect of
      efferent inhibition over prolonged periods of acoustic stimulation is less well
      documented, especially as observed by transient evoked otoacoustic emission
      (TEOAE) suppression. The present study evaluated the relationship between the
      duration of contralateral acoustic stimulation and the suppression of TEOAE in 10
      normal-hearing adults. TEOAE recordings with linear clicks (60 dB SPL) were
      measured at four intervals during 15 min of continuous contralateral white noise
      (45 dB SL), followed by two post-noise recordings. An identical within-subject
      control condition was recorded without contralateral noise. Experimental and
      control measurements were repeated three times, on separate days. Results
      revealed significant and sustained TEOAE amplitude reduction for the entire
      duration of contralateral stimulation. Suppression increased gradually for the
      duration of contralateral noise presented, but not sufficiently to be
      statistically significant. Three minutes after noise termination, TEOAE
      amplitudes increased to values significantly above control recordings. The MOCS
      is able to sustain suppression over a prolonged duration of contralateral
      stimulation, supporting its role as an active modulator of outer hair cell
      mechanics during ongoing stimuli.

PMID- 19401225
TI  - Dissecting natural sensory plasticity: hormones and experience in a maternal
      context.
AB  - There is a growing consensus that the auditory system is dynamic in its
      representation of behaviorally relevant sounds. The auditory cortex in particular
      seems to be an important locus for plasticity that may reflect the memory of such
      sounds, or functionally improve their processing. The mechanisms that underlie
      these changes may be either intrinsic because they depend on the receiver's
      physiological state, or extrinsic because they arise from the context in which
      behavioral relevance is gained. Research in a mouse model of acoustic
      communication between offspring and adult females offers the opportunity to
      explore both of these contributions to auditory cortical plasticity in a natural
      context. Recent works have found that after the vocalizations of infant mice
      become behaviorally relevant to mothers, auditory cortical activity is
      significantly changed in a way that may improve their processing. Here we
      consider the hypothesis that maternal hormones (intrinsic factor) and sensory
      experience (extrinsic factor) contribute together to drive these changes,
      focusing specifically on the evidence that well-known experience-dependent
      mechanisms of cortical plasticity can be modulated by hormones.

PMID- 19401227
TI  - Optimization of metabolic pathways for bioconversion of lignocellulose to ethanol
      through genetic engineering.
AB  - The optimization of metabolic pathways is of fundamental importance for
      strategies aimed at improving the economics and yield of the lignocellulose-to
      ethanol processes. Although Escherichia coli is capable of metabolizing a wide
      variety of substrates including hexoses and pentoses, its hexose metabolism is
      inferior to that of Zymomonas mobilis, an obligate, ethanologenic bacterium. We
      therefore inserted and expressed Z. mobilis genes encoding essential enzymes
      involved in the fermentation pathway, alcohol dehydrogenase II (adh II) and
      pyruvate decarboxylase (pdc), into E. coli, resulting in increased cell growth
      and ethanol production. Ethanol concentrations of >30 g/L were obtained on 10%
      glucose. Additionally, since pyruvate is mainly assimilated through pyruvate
      formate lyase (pfl) and forms formic acid and acetyl coenzyme A, metabolic
      redirection was attempted through gene knockout by Red-mediated recombination to
      decrease the byproducts of pyruvate metabolism. Under microaerobic conditions,
      pflA- and pflB-mutants produced more ethanol (163% and 207%, respectively)
      relative to the parent strain, using glucose as a carbon source.

PMID- 19401228
TI  - Oxidative stress contributes to silica nanoparticle-induced cytotoxicity in human
      embryonic kidney cells.
AB  - In order to elucidate the nanoparticle-induced cytotoxicity and its mechanism,
      the effects of 20 and 50 nm silica nanoparticles on cultured human embryonic
      kidney (HEK293) cells were investigated. Cell viability, mitochondrial function,
      cell morphology, reactive oxygen species (ROS), glutathione (GSH), thiobarbituric
      acid reactive substance (TBARS), cell cycle and apoptosis were assessed under
      control and silica exposed conditions. Exposure to 20 or 50 nm SiO(2)
      nanoparticles at dosage levels between 20 and 100 microg/ml decreased cell
      viability in a dose-dependent manner. Median lethal dose (LD(50)) of 24h exposure
      was 80.2+/-6.4 and 140.3+/-8.6 microg/ml for 20 and 50 nm SiO(2) nanoparticles,
      respectively. Morphological examination revealed cell shrinkage and nuclear
      condensation after SiO(2) nanoparticle exposure. Increase in intracellular ROS
      level and reduction in GSH content were also observed in SiO(2) nanoparticle
      exposed HEK293 cells. Increase in the amount of TBARS suggested an elevated level
      of lipid peroxidation. Flow cytometric analysis showed that SiO(2) nanoparticles
      can cause G2/M phase arrest and apoptotic sub-G1 population increase in a dose
      dependent manner. In summary, exposure to SiO(2) nanoparticles resulted in a dose
      dependent cytotoxicity in cultured HEK293 cells that was associated with
      increased oxidative stress.

PMID- 19401229
TI  - Snakehead-fish cell line, SSN-1 (Ophicephalus striatus) as a model for cadmium
      genotoxicity testing.
AB  - The purpose of this study is to evaluate the potential of snakehead-fish cell
      line (SSN-1 cells) derived from a striped snakehead (Ophicephalus striatus) as a
      model in the genotoxic assessment of cadmium (Cd). The first approach employed
      was to determine the contaminated Cd levels in commercial snakehead fish by the
      Graphite Atomic Absorption Spectrophotometer. In the second approach, the
      sensitivity of SSN-1 cells to cytotoxicity and genotoxicity of Cd was assessed by
      Trypan blue and micronucleus assays following 24, 48, and 72 h of incubation
      period. Exposure of SSN-1 cells to four increasing Cd concentrations ranging from
      0.005 to 5 ppm for 72 h did not affect their survival as compared to the control
      cells. The Cd uptake by SSN-1 cells showed a concentration-dependent increase in
      intracellular Cd levels. Three non-cytotoxic Cd concentrations (0.05, 0.5, and 5
      ppm) showed a concentration-dependent genotoxic effect, compared to relevant
      control cells. Both micronucleus frequencies and cadmium uptake levels by SSN-1
      cells depended on exposure concentrations. These results showed that the SSN-1
      cells are suitable for use as a model for in vitro Cd genotoxicity testing.

PMID- 19401230
TI  - CCL21-induced calcium transients and proliferation in primary mouse astrocytes:
      CXCR3-dependent and independent responses.
AB  - CCL21 is a homeostatic chemokine that is expressed constitutively in secondary
      lymph nodes and attracts immune cells via chemokine receptor CCR7. In the brain
      however, CCL21 is inducibly expressed in damaged neurons both in vitro and in
      vivo and has been shown to activate microglia in vitro, albeit not through CCR7
      but through chemokine receptor CXCR3. Therefore, a role for CCL21 in CXCR3
      mediated neuron-microglia signaling has been proposed. It is well established
      that human and mouse astrocytes, like microglia, express CXCR3. However, effects
      of CCL21 on astrocytes have not been investigated yet. In this study, we have
      examined the effects of CCL21 on calcium transients and proliferation in primary
      mouse astrocytes. We show that similar to CXCR3-ligand CXCL10, CCL21 (10(-9) M
      and 10(-8) M) induced calcium transients in astrocytes, which were mediated
      through CXCR3. However, in response to high concentrations of CCL21 (10(-7) M)
      calcium transients persisted in CXCR3-deficient astrocytes, whereas CXCL10 did
      not have any effect in these cells. Furthermore, prolonged exposure to CXCL10 or
      CCL21 promoted proliferation of wild type astrocytes. Although CXCL10-induced
      proliferation was absent in CXCR3-deficient astrocytes, CCL21-induced
      proliferation of these cells did not significantly differ from wild type
      conditions. It is therefore suggested that primary mouse astrocytes express an
      additional (chemokine-) receptor, which is activated at high CCL21
      concentrations.

PMID- 19401231
TI  - A novel male-specific DNA sequence in the common carp, Cyprinus carpio.
AB  - In this study, we identified a sex-specific DNA marker using randomly amplified
      polymorphic DNA (RAPD) fingerprinting in Yellow River carps (Cyprinus carpio from
      the Yellow River). Two hundred and twenty random primers were used in pooled DNA
      samples and individual DNA samples from male and female fish for RAPD
      fingerprinting. When using the primer S2107, a novel sex-specific PCR product was
      identified in all male individuals. DNA sequencing revealed that this 909 bp long
      DNA fragment has a low similarity to a repetitive sequence in zebrafish Danio
      rerio. In order to confirm the amplification results, two primers were designed
      within the male-specific sequence in order to amplify the sex-specific fragment
      from genomic DNA of male and female carps for sexing by PCR. The results
      indicated bands specific for males but not females. Respective results were
      obtained in dot blot and Southern blot hybridization experiments when using this
      sex-specific fragment as the probe. The sex-specific pattern was observed in 30
      individuals from three separate common carp stocks, suggesting that the sequence
      is conserved in common carp species. However, no hybridization signals were found
      in grass carps Ctenopharyngodon idella, which are related to common carps. We
      submit to use this sex-specific fragment as a marker to rapidly and accurately
      identify the gender of Yellow River C. carpio. Furthermore, the sex-specific
      chromosome region may be characterized and used to study mechanisms of chromosome
      evolution in this fish species.

PMID- 19401232
TI  - Specific detection and quantification of the phytopathogenic agent 'Candidatus
      Phytoplasma prunorum'.
AB  - 'Candidatus Phytoplasma prunorum' is a wall-less bacterium associated with
      European stone fruit yellows (ESFY), a severe disease of Prunus spp. (mainly
      apricot and Japanese plum trees). It can be spread by one insect vector,
      Cacopsylla pruni, and by the trade of infected material. The availability of PCR
      based methods allowing a sensitive and specific detection of 'Ca. P. prunorum' is
      crucial for this phytoplasma because, at present, it is uncultured and cannot be
      detected serologically. We developed a PCR test which, in contrast to the
      existing detection tools, provides a fast, specific and sensitive detection of
      'Ca. P. prunorum' in plants and insects. For studies requiring an absolute
      quantification of the phytoplasma titer, the same primers were used to develop a
      real-time PCR assay, including a standard for C. pruni. The sensitivity of these
      molecular tools was compared by serial dilutions and their specificity was
      assessed both in silico and experimentally for reference strains and field
      samples of the closely related phytoplasma 'Ca. P. prunorum', 'Ca. P. pyri' (pear
      decline agent) and 'Ca. P. mali' (apple proliferation agent), as well as for
      representative strains of the 'Ca. Phytoplasma' genus.

PMID- 19401233
TI  - Purification and characterisation of the breast cancer metastasis suppressor,
      BRMS1.
AB  - The breast cancer metastasis suppressor 1 (BRMS1) is a member of a family of
      proteins that actively suppress tumour metastasis. Understanding BRMS1 mediated
      metastasis suppression is critical to the development of new therapies designed
      to prevent and treat patients with late stage breast cancer. To aid research into
      the functional aspects that underpin BRMS1 mediated metastasis suppression we
      have expressed and purified recombinant BRMS1 and produced BRMS1 polyclonal
      antibodies. Using these antibodies to immunoprecipitate endogenous BRMS1
      containing complexes from MCF7 breast cancer cell lines we have identified, by
      mass spectrometry, the small heat shock protein Hsp27 in complex with BRMS1. We
      also show that the expression of both BRMS1 and Hsp27 are inversely correlated
      with metastatic potential.

PMID- 19401234
TI  - Comparative structural studies on Lys49-phospholipases A(2) from Bothrops genus
      reveal their myotoxic site.
AB  - Phospholipases A(2) (PLA(2)s) are membrane-associated enzymes that hydrolyze
      phospholipids at the sn-2 position, releasing lysophospholipids and free fatty
      acids. Phospholipase A(2) homologues (Lys49-PLA(2)s) are highly myotoxic and
      cause extensive tissue damage despite not showing measurable catalytic activity.
      They are found in different snake venoms and represent one third of bothropic
      venom composition. The importance of these toxins during envenomation is related
      to the pronounced local myotoxic effect they induce since this effect is not
      neutralized by serum therapy. We present herein three structures of Lys49-PLA(2)s
      from Bothrops genus snake venom crystallized under the same conditions, two of
      which were grown in the presence of alpha-tocopherol (vitamin E). Comparative
      structural analysis of these and other Lys49-PLA(2)s showed two different
      patterns of oligomeric conformation that are related to the presence or absence
      of ligands in the hydrophobic channel. This work also confirms the biological
      dimer indicated by recent studies in which both C-termini are in the dimeric
      interface. In this configuration, we propose that the myotoxic site of these
      toxins is composed by the Lys 20, Lys115 and Arg118 residues. For the first time,
      a residue from the short-helix (Lys20) is suggested as a member of this site and
      the importance of Tyr119 residue to myotoxicity of bothropic Lys49-PLA(2)s is
      also discussed. These results support a complete hypothesis for these PLA(2)s
      myotoxic activity consistent with all findings on bothropic Lys49-PLA(2)s studied
      up to this moment, including crystallographic, bioinformatics, biochemical and
      biophysical data.

PMID- 19401235
TI  - The crystal structure of the secreted aspartic protease 1 from Candida
      parapsilosis in complex with pepstatin A.
AB  - Opportunistic pathogens of the genus Candida cause infections representing a
      major threat to long-term survival of immunocompromised patients. Virulence of
      the Candida pathogens is enhanced by production of extracellular proteolytic
      enzymes and secreted aspartic proteases (Saps) are therefore studied as potential
      virulence factors and possible targets for therapeutic drug design. Candida
      parapsilosis is less invasive than C. albicans, however, it is one of the leading
      causative agents of yeast infections. We report three-dimensional crystal
      structure of Sapp1p from C. parapsilosis in complex with pepstatin A, the
      classical inhibitor of aspartic proteases. The structure of Sapp1p was determined
      from protein isolated from its natural source and represents the first structure
      of Sap from C. parapsilosis. Overall fold and topology of Sapp1p is very similar
      to the archetypic fold of monomeric aspartic protease family and known structures
      of Sap isoenzymes from C. albicans and Sapt1p from C. tropicalis. Structural
      comparison revealed noticeable differences in the structure of loops surrounding
      the active site. This resulted in differential character, shape, and size of the
      substrate binding site explaining divergent substrate specificities and inhibitor
      affinities. Determination of structures of Sap isoenzymes from various species
      might contribute to the development of new Sap-specific inhibitors.

PMID- 19401236
TI  - Covalent modification of chitin with silk-derivatives acts as an amphiphilic self
      organizing template in nacre biomineralisation.
AB  - Molluscs have a well-deserved reputation for being expert mineralizers of various
      shell types such as nacre. Nacre is defined as regularly arranged layers and
      stacks of approximately 0.5 microm thick aragonite platelets that are
      extracellularly formed within a complex mixture of organic matrix. The control of
      species-specific layer thickness by the animal is still enigmatic. Despite the
      recent findings on the periodic layer-by-layer structures of chitin layers and
      silk-like protein layers in nacre-type biominerals, little is known about how the
      interface is defined between two different layers. In this paper, we demonstrate
      the presence of covalently attached, hydrophobic amino acid side chains in the
      chitin matrix in the bivalve mollusc Mytilus galloprovincialis by the combination
      of infrared spectroscopy and mass spectroscopy. The accumulation of the modified
      chitin matrix at the interface is quantified by the critical aggregate
      concentration of the purified chitin matrix, which is approximately an order of
      magnitude smaller than that of pure chitin. Our finding suggests an active role
      of such chemically modified chito-oligosaccharides in the creation of a defined
      interface and guidance of the periodic matrix textures, which would result in
      unique material properties of natural mollusc shells.

PMID- 19401237
TI  - Sequential cladogenesis of the reef fish Pomacentrus moluccensis (Pomacentridae)
      supports the peripheral origin of marine biodiversity in the Indo-Australian
      archipelago.

PMID- 19401238
TI  - The Antarctic hemoglobinless icefish, fifty five years later: a unique
      cardiocirculatory interplay of disaptation and phenotypic plasticity.
AB  - The teleostean Channichthyidae (icefish), endemic stenotherms of the Antarctic
      waters, perennially at or near freezing, represent a unique example of
      disaptation among adult vertebrates for their loss of functional traits,
      particularly hemoglobin (Hb) and, in some species, cardiac myoglobin (Mb), once
      considered to be essential-life oxygen-binding chromoproteins. Conceivably, this
      stably frigid, oxygen-rich habitat has permitted high tolerance of disaptation,
      followed by subsequent adaptive recovery based on gene expression reprogramming
      and compensatory responses, including an alternative cardio-circulatory design,
      Hb-free blood and Mb-free cardiac muscle. This review revisits the functional
      significance of the multilevel cardio-circulatory compensations (hypervolemia,
      near-zero hematocrit and low blood viscosity, large bore capillaries, increased
      vascularity with great capacitance, cardiomegaly with very large cardiac output,
      high blood flow with low systemic pressure and systemic resistance) that
      counteract the challenge of hypoxemic hypoxia by increasing peripheral oxygen
      transcellular movement for aerobic tissues, including the myocardium.
      Reconsidered in the context of recent knowledge on both polar cold adaptation and
      the new questions related to the advent of nitric oxide (NO) biology, these
      compensations can be interpreted either according to the "loss-without-penalty"
      alternative, or in the context of an excessive environmental oxygen supply at low
      cellular cost and oxygen requirement in the cold. Therefore, rather than
      reflecting oxygen limitation, several traits may indicate structural
      overcompensation of oxygen supply reductions at cell/tissue levels. At the
      multilevel cardio-circulatory adjustments, NO is revealing itself as a major
      integrator, compensating disaptation with functional phenotypic plasticity, as
      illustrated by the heart paradigm. Beside NOS-dependent NO generation, recent
      knowledge concerning Hb/Mb interplay with NO and nitrite has revealed unexpected
      functions in addition to the classical respiratory role of these proteins. In
      fact, nitrite, a major biologic reservoir of NO, generates it through deohyHb-
      and deoxyMb-dependent nitrite reduction, thereby regulating hypoxic vasodilation,
      cellular respiration and signalling. We suggest that both Hb and Mb are involved
      as nitrite reductases under hypoxic conditions in a number of cardiocirculatory
      processes. On the whole, this opens new horizons in environmental and
      evolutionary physiology.

PMID- 19401239
TI  - The larval alimentary canal of the Antarctic insect, Belgica antarctica.
AB  - On the Antarctica continent the wingless midge, Belgica antarctica (Diptera,
      Chironomidae) occurs further south than any other insect. The digestive tract of
      the larval stage of Belgica that inhabits this extreme environment and feeds in
      detritus of penguin rookeries has been described for the first time. Ingested
      food passes through a foregut lumen and into a stomodeal valve representing an
      intussusception of the foregut into the midgut. A sharp discontinuity in
      microvillar length occurs at an interface separating relatively long microvilli
      of the stomodeal midgut region, the site where peritrophic membrane originates,
      from the midgut epithelium lying posterior to this stomodeal region. Although
      shapes of cells along the length of this non-stomodeal midgut epithelium are
      similar, the lengths of their microvilli increase over two orders of magnitude
      from anterior midgut to posterior midgut. Infoldings of the basal membranes also
      account for a greatly expanded interface between midgut cells and the hemocoel.
      The epithelial cells of the hindgut seem to be specialized for exchange of water
      with their environment, with the anterior two-thirds of the hindgut showing
      highly convoluted luminal membranes and the posterior third having a highly
      convoluted basal surface. The lumen of the middle third of the hindgut has a
      dense population of resident bacteria. Regenerative cells are scattered
      throughout the larval midgut epithelium. These presumably represent stem cells
      for the adult midgut, while a ring of cells, marked by a discontinuity in nuclear
      size at the midgut-hindgut interface, presumably represents stem cells for the
      adult hindgut.

PMID- 19401240
TI  - Acute ethics: risk assessment and the Doctrine of Double Effect in a referral to
      on-call urology.
AB  - The Doctrine of Double Effect has been described as often used in medicine and
      surgery but is seldom described outside the palliative medicine context. This
      paper presents a possible clinically focussed illustration of the doctrine of
      double effect used in an acute urological setting. The authors describe the case
      of an elderly patient with significant dementia and haematuria who required
      anticoagulation. Implicit double effect reasoning may have helped the surgical
      team reach their initial decision with regard to a treatment plan, reconciling a
      duty to beneficence with a duty not to cause harm. This short case is offered as
      a stimulus for further discussion over the role of duty-based ethical reasoning
      in the acute surgical setting. It also highlights a possible need for more
      detailed case-analysis in identifying areas of interest in surgical ethics.

PMID- 19401241
TI  - Surgical management of gastric cicatrisation resulting from corrosive ingestion.
AB  - BACKGROUND: Caustic injury to the stomach can be complicated by gastric stenosis.
      We review our experience with surgical management of symptomatic gastric
      stenosis. METHODS: This is a retrospective chart review of patients who underwent
      surgery for gastric stenosis within 6 weeks to 26 months following corrosive
      ingestion. The data analyzed included the extent of cicatrisation, surgical
      procedure performed and outcome. Preoperative evaluation in these patients
      included a barium contrast study and upper gastrointestinal endoscopy. RESULTS:
      Main presenting symptoms were nonbilious vomiting, early satiety, dysphagia and
      significant weight loss. Antropyloric strictures were present in 28 (64%)
      patients, total gastric involvement was seen in 16 (36%) patients, associated
      esophageal stenosis was present in 18 (40.91%) patients. Surgical procedures
      performed included distal gastrectomy with Billroth1 reconstruction in 31.82%,
      distal gastrectomy with Roux-en-Y reconstruction in 20.45%, stricturoplasty in
      11.36%, subtotal gastrectomy in 18.18% and total gastrectomy with pouch
      reconstruction in another 18.18% patients. Complications encountered were
      pneumonitis in 18.18%, wound infection in 11.36%, intra-abdominal infection,
      anastomotic breakdown, reactivation of pulmonary tuberculosis and dumping
      syndrome, each in 2.27% patients. One patient (2.27%) died. CONCLUSION: Surgical
      procedure should be tailored according to the extent of gastric involvement.
      Surgical resection is feasible and safe. Our results suggest that satisfactory
      outcome could be expected with different therapeutic modalities based on degree
      of cicatrisation.

PMID- 19401242
TI  - Hereditary leukonychia totalis, acanthosis-nigricans-like lesions and hair
      dysplasia: a new syndrome?
AB  - Leukonychia is an ungueal discoloration or dyschromia. The hereditary form is
      rare. In the observations reported in the literature, leukonychia was total or
      sub-total, and was sometimes associated to other various symptoms. We report an
      original observation of hereditary leukonychia totalis in a father and two of his
      children, associated with acanthosis-nigricans-like lesions and hair dysplasia.
      These symptoms were also present in eight other members of the same family.

PMID- 19401243
TI  - Relation of regional articular cartilage morphometry and meniscal position by MRI
      to joint space width in knee radiographs.
AB  - OBJECTIVE: To ascertain the contribution of articular cartilage morphometry and
      meniscal position on MRI to joint space width (JSW) measured in the Lyon schuss
      radiograph of the knee. DESIGN: 62 obese women with knee OA and 99 non-obese
      female controls (mean age 56.6 years) were imaged using 3T MRI and coronal water
      excitation spoiled gradient echo sequences. Segmentation of femorotibial
      cartilage morphology and regional morphometric analysis was performed using
      custom software. Meniscal position was measured quantitatively in sagittal and
      coronal planes. Minimum space width (mJSW) was measured in the Lyon Schuss knee
      radiograph; Kellgren and Lawrence grades (KLG) were assigned on standing
      anteroposterior knee films. The relative contribution of regional cartilage
      thickness and meniscal position to mJSW was assessed initially in univariate
      models and subsequently with multivariable modelling. RESULTS: 65% of the
      variation in mJSW was explained by regional cartilage thickness measures,
      different KLG and meniscal coverage. Of these measures the medial tibia cartilage
      thickness measures and central region of the central medial femur (ccMF) play a
      consistent role in variations in mJSW observed across all KLG. Further ccMF and
      the addition of percent meniscal coverage to this model explains the remaining
      differences in mean mJSW found between those subjects with definite joint space
      narrowing (KLG3) and those without OA. CONCLUSION: The variation in radiographic
      mJSW is best described by five regional cartilage thickness measures and percent
      meniscal coverage. The magnitude of each measures contribution differs according
      to radiographic severity with more variability explained by cartilage thickness
      of ccMF cartilage thickness and percent meniscal coverage with more severe
      disease.

PMID- 19401244
TI  - Does isolated patellofemoral osteoarthritis matter?
AB  - OBJECTIVES: To describe the structure-pain and structure-function associations in
      isolated patellofemoral osteoarthritis (PF OA). DESIGN: Population-based study of
      819 adults aged > or =50 years with knee pain. The severity of knee pain,
      stiffness and disability were measured using the Western Ontario and McMaster
      Osteoarthritis Index (WOMAC). Three radiographic views of the knee were obtained.
      RESULTS: Isolated PF OA was mild in 142 participants and moderate/severe in 44.
      Mean WOMAC scores for pain, stiffness and function were associated with
      radiographic severity of PF OA (F(2,389)=4.7, P=0.01; F(2,392)=4.5, P=0.012 and
      F(2,392)=6.1, P=0.002, respectively, adjusted for age, gender, and body mass
      index (BMI)). Post-hoc tests demonstrated statistically significant differences
      for mean pain, stiffness and function score between those with mild PF OA and
      those with normal X-rays. In task-specific items there was evidence of a stepped
      response, the proportion of participants with moderate/severe/extreme pain or
      difficulty in performing everyday tasks increasing with the severity of PF OA.
      The strongest association was observed for pain going up and down stairs (age
      gender-BMI adjusted odds ratio (OR) 3.0; 95% confidence interval (CI) 1.4,6.6.
      Functional tasks most strongly related to radiographic severity were: descending
      stairs (OR 3.2; (CI 1.5,6.5)), getting in/out of the bath (3.2; 1.5,6.6), getting
      in/out of a car (3.0; 1.4,6.1). CONCLUSIONS: Mild isolated PF OA is significantly
      associated with symptoms of pain, stiffness and functional limitation. Further
      research on its recognition in clinical practice and the development of targeted
      treatments to prevent or slow progression are warranted.

PMID- 19401245
TI  - In good company...Now what about that impact factor?

PMID- 19401246
TI  - Child health in child care: a multi-state survey of Head Start and non-Head Start
      child care directors.
AB  - INTRODUCTION: Directors of Head Start (HS) and non-Head Start (non-HS) child care
      centers were surveyed to compare health consultation and screening for and
      prevalence of health risks among enrolled children. METHODS: Directors of
      licensed centers from five states were surveyed from 2004 to 2005. Data were
      analyzed using cross-tabulation and logistic regression techniques. RESULTS: A
      total of 2753 surveys were completed. HS centers were more likely than non-HS
      centers to consult health professionals (P < .0001). More than 90% of HS centers
      screened for health problems compared with 64.9% of non-HS centers (P < .0001).
      Almost all HS centers provided parents with child health information. Children at
      HS centers were at high risk for dental problems. Less than 3% of HS center
      directors, versus 11.3% of non-HS directors (P < .0002), reported TV viewing for
      more than an hour a day. DISCUSSION: Children in HS centers were more likely to
      receive health consultations and screenings, were at higher risk for dental
      problems, and watched less TV compared with children in non-HS centers. HS
      centers promoted health significantly more frequently than did non-HS centers.

PMID- 19401247
TI  - Depiction of food as having drug-like properties in televised food advertisements
      directed at children: portrayals as pleasure enhancing and addictive.
AB  - INTRODUCTION: The purpose of this study was to examine food commercials airing
      during children's TV programming for portrayals of behaviors associated with
      substance use, violence, disrespect, and stealing. It was hypothesized that these
      behaviors would be present and would be more frequent in commercials advertising
      specific products (e.g., ready-to-eat cereals) than for those advertising
      restaurants (e.g., fast food). METHOD: A content analysis of 147 food commercials
      televised during children's TV programming on U.S. broadcast networks examined
      commercials for behaviors associated with substance use behavior, physical
      violence, and other problematic behaviors for children. RESULTS: Commercials
      contained depictions of exaggerated pleasure sensation and dependency/addiction,
      portrayals of physical violence, trickery, thievery/stealing, fighting and taking
      extreme measures to obtain a food, and treating adults with disrespect. More
      portrayals appeared in commercials for high-sugar cereals than in those for fast
      food restaurants. DISCUSSION: Findings raise concern about the presence of this
      content in televised food advertisements targeting children and serve to alert
      pediatric health professionals and other child health advocates to take a closer
      look at this issue.

PMID- 19401248
TI  - Brief report: language ability and school functioning of youth perinatally
      infected with HIV.
AB  - INTRODUCTION: The purpose of this article is to describe the language ability and
      school functioning of early adolescents with perinatal HIV/AIDS. METHOD:
      Participants included 43 youths, 9-15 years, and their primary caregivers. Youths
      completed the Peabody Picture Vocabulary Test (PPVT) and the Reading Subtest of
      the Wide Range Achievement Test (WRAT3) and were interviewed regarding their
      future educational aspirations and parental supervision and involvement with
      homework. Caregivers were interviewed regarding the child's school achievement,
      parental supervision and monitoring, and educational aspirations for their child.
      RESULTS: Fifty-four percent of youths scored below average (<25th percentile) on
      the PPVT, and 29% scored below the 10th percentile; 40% scored below average
      (<25th percentile) on the WRAT3, and 24% scored below the 10th percentile. Scores
      were associated with parental monitoring and educational aspirations. DISCUSSION:
      Youths performed poorly on tests of verbal and reading ability, although their
      scores were not dissimilar to those of other samples of inner-city youths. Future
      research should attempt to isolate the impact of HIV disease on intellectual and
      school functioning of HIV+ youths.

PMID- 19401249
TI  - Parents' perspectives of surgery for a child who has cerebral palsy.
AB  - INTRODUCTION: This article explores parents' experiences when their child who is
      disabled with cerebral palsy was going through a surgical procedure. The
      literature suggests that parents' uncertainty is a consistent concept regarding
      the families' experiences in postoperative recovery unit. METHODS: A hermeneutic
      phenomenological in-depth interview was used, and data are analyzed and
      interpreted to reflect the words and actions of the participants. Parents of nine
      children with cerebral palsy were interviewed during recovery or after the
      children had recovered from the surgery. RESULTS: The parents reported feeling
      vulnerable and helpless in a situation where children cannot express their
      concerns, and parents were fearful of the consequences of surgery, because they
      were not familiar with what is going on in the hospital. Extreme tiredness is an
      unrelenting condition in the experience of these parents, being constantly
      available for the child but also being strong for the child's sake. DISCUSSION:
      Parents perceived that health professionals, especially those with limited
      experience with children with disabilities, did not understand parents or see
      parents as unique individuals who are linked to their child in a very special
      way. The importance of being aware of parents' previous experiences and the need
      to offer both parents and the child emotional support is clear from this study.

PMID- 19401250
TI  - Use of continuous insulin infusion pumps in young children with type 1 diabetes:
      a systematic review.
AB  - INTRODUCTION: Although insulin pump therapy has been successful in adults and
      adolescents, its use has been limited in young children because of perceived risk
      of severe or frequent hypoglycemia. The purpose of this review is to evaluate the
      safety and efficacy of continuous subcutaneous insulin infusion (CSII) in young
      children with type 1 diabetes. METHODS: We searched Medline, PubMed, and CINAHL
      for clinical trials comparing multiple-dose injection therapy to CSII therapy in
      children 6 years of age or younger who were diagnosed with type 1 diabetes at
      least 6 months prior to study. Primary outcome measures were glycosylated
      hemoglobin (HbA1c) and hypoglycemic episodes. Other outcomes of interest were
      quality of life and parental satisfaction. RESULTS: Most studies showed
      significant improvements in HbA1c and trends of decreased hypoglycemia. Quality
      of life improved in most CSII groups. Parental satisfaction with therapy was
      evidenced by continuation of CSII after study completion. DISCUSSION: Current
      evidence indicates CSII is a safe and effective method of insulin delivery in
      young children. When parents are highly motivated, CSII should be offered as a
      mode of insulin delivery for this age group.

PMID- 19401251
TI  - The case of the silent crippler.

PMID- 19401252
TI  - Not exactly a pain in the neck.

PMID- 19401253
TI  - Practice guideline: evaluation and management of abnormal vaginal bleeding in
      adolescents.

PMID- 19401254
TI  - Use of probiotics in pediatrics.

PMID- 19401255
TI  - Practitioner preceptors: a shortage of willing mentors.

PMID- 19401256
TI  - Measuring pain in adolescents.

PMID- 19401257
TI  - Environmental occurrence and degradation of the herbicide n-chloridazon.
AB  - A sampling campaign was carried out for n-chloridazon (n-CLZ) and its degradation
      product desphenyl-chloridazon (DPC) in the Hesse region (Germany) during the year
      2007: a total of 548 environmental samples including groundwater, surface water
      and wastewater treatment plant (WWTP) effluent were analysed. Furthermore,
      aerobic degradation of n-CLZ has been studied utilising a fixed bed bioreactor
      (FBBR). In surface water, n-CLZ was detected at low concentrations (average
      0.01+/-0.06mugL(-1); maximum 0.89mugL(-1)) with a seasonal peak, whereas DPC was
      present throughout the year at much higher concentrations (average 0.72+/
      0.81mugL(-1); maximum 7.4mugL(-1)). Higher n-CLZ concentrations were observed in
      the North compared with South Hesse, which is ascribed to a higher density of
      agricultural areas. Furthermore, methylated DPC (Me-DPC), another degradation
      product, was detected in surface water. In the degradation test, n-CLZ was
      completely converted to DPC at all concentrations tested (Me-DPC was not formed
      under the test conditions). DPC was resistant to further degradation during the
      whole experimental period of 98 days. The results obtained suggest persistence
      and high dispersion of DPC in the aquatic environment.

PMID- 19401258
TI  - Evaluation of two methods for quantification of hsp70 mRNA from the waterborne
      pathogen Cryptosporidium parvum by reverse transcription real-time PCR in
      environmental samples.
AB  - We optimized and evaluated two mRNA extraction methods to quantify induced hsp70
      mRNA from viable and injured Cryptosporidium parvum oocysts by reverse
      transcription quantitative real-time PCR (RT-qPCR) in raw and treated manure.
      Methods based on guanidinium isothiocyanate/phenol/chloroform (GITC-PC)
      purification and direct mRNA extraction with magnetic oligo(dT)25-coated beads
      were evaluated for applicability and sensitivity. Both methods proved to be
      suitable for processing manure samples. With washed manure samples and oocyst
      disruption by bead beating for 165 s in time intervals with cumulative pooling of
      the lysate fractions, optimum RT-qPCR results were achieved. On average, 2.6
      times more hsp70 mRNA was detected with the oligo(dT)25 method in comparison to
      the GITC-PC based method using fresh oocysts, whereas less mRNA was detected in
      aged oocysts. For fresh oocysts, analytical and method detection limits for the
      oligo(dT)25 based method were 1.7 cDNA copies/qPCR reaction and 5150 oocysts/mL
      manure, and for the GITC-PC based method 17 cDNA copies/qPCR reaction and 4950
      oocysts/mL, respectively. In 12 months old oocysts with reduced viability, mRNA
      was occasionally detected only by the GITC-PC based method. Failure of or reduced
      detection with the oligo(dT)25 based method was apparently a result of weakened
      oocyst walls leading to quicker release of mRNA and therefore mRNA shredding by
      bead beating in the relatively long stretch between the capture sequence and the
      RT-qPCR target sites.

PMID- 19401259
TI  - Historical trends of dioxin-like compounds and heavy metals in sediments buried
      in a reservoir in central Taiwan.
AB  - Polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated dibenzofuran (PCDF),
      polychlorinated biphenyl (PCB) and heavy metal concentrations were analyzed at 1
      2 cm intervals in a sediment core collected from a reservoir to evaluate
      anthropogenic pollution history in central Taiwan. The age of the sediment core
      was estimated from the sedimentation rate (0.44-0.52 cm year(-1), calculated by
      (210)Pb and (137)Cs analysis). The highest PCDD/F (4.10 ng TEQ(WHO)kg(-1)d.w.)
      and PCB (0.345ngTEQ(WHO)kg(-1)d.w.) concentrations occurred around 1985 (i.e. at
      a downcore depth of 10-12 cm). Our results also demonstrated that PCDD/F and PCB
      concentrations in the reservoir sediment core started to decrease at a depth of 8
      10 cm (estimated year: 1989). This may be attributed to the fact that the Taiwan
      Environmental Protection Administration (EPA) proposed the regulation of
      pentachlorophenol (PCP) production and PCB manufacture in 1983 and 1988,
      respectively. In addition, a linear increasing trend in metal content with time
      (towards the core top) was observed for several metals (Zn, Cr, Cu, Cd and Pb).
      Results of the enrichments rates of anthropogenic metals indicated that the
      metal/alumina (M/Al) ratios of Zn, Cd and Pb in sediment cores exceeded those in
      crust compositions by 47%, 59% and 78%, respectively. The results revealed that
      considerable amounts of heavy metals were carried into the reservoir following
      significant immigration during the Chinese civil war (1950).

PMID- 19401260
TI  - Cardiac MRI studies of transient left ventricular apical ballooning syndrome
      (takotsubo cardiomyopathy): a systematic review.
AB  - BACKGROUND: Since its first description in 1991, many cases of transient left
      ventricular apical ballooning syndrome (TLVABS) have been described, but the use
      of cardiac MRI in this condition is much more recent. METHODS AND RESULTS: We
      performed a systematic review of the present literature in the MEDLINE and EMBASE
      databases for relevant case series of TLVABS (>or=5 reported original cases, MRI
      analysis in the acute phase) and summarized the main results in a narrative
      synthesis. Only 8 studies met the eligible criteria, counting 176 patients
      (women: 95%; age: 68, stress trigger: 80%). MRI assessed an improvement of mean
      left ventricular ejection fraction from 39 (in the acute phase) to 64% (in the
      recovery phase). A right ventricular dysfunction was reported in 38%, a
      myocardial oedema in 81% and an apical thrombus in 5%. CONCLUSIONS: Although
      cardiac MRI is a very useful and inescapable tool in the management of TLVABS,
      there is no large published study concerning this topic. A systematic and
      multicentric register of TLVABS studied by cardiac MRI is necessary.

PMID- 19401261
TI  - Molecular characterization of the black Aspergillus isolates responsible for
      ochratoxin A contamination in grapes and wine in relation to taxonomy of
      Aspergillus section Nigri.
AB  - This work examines ochratoxigenic mycobiota in grapes by ap-PCR analysis sequence
      analysis of the ITS and IGS regions and ability to produce OTA. A comparison was
      also made with many reference strains of Aspergillus section Nigri. Based on ap
      PCR profiles, derived from two microsatellite primers, three main groups were
      obtained by UPGMA cluster analysis corresponding to A. carbonarius, A. niger and
      A. tubingensis. The cophenetic correlation values corresponding to ap-PCR UPGMA
      analysis revealed a higher genetic variability in A. niger and A. tubingensis
      than in A. carbonarius. In addition, no genotypical differences could be
      established between OTA producers and nonproducers in all species analysed.
      Phylogenetic relationships inferred from ITS and IGS sequences are, mostly,
      congruent with earlier works. A. niger and A. tubingensis strains were closely
      related, but not identical, and they clustered into two distinct groups within
      the A. niger aggregate. Sequence analysis also showed genetic divergences between
      strains of A. foetidus and the rest of the Aspergillus section Nigri.
      Additionally, the phylogenetic analysis was consistent in separating a new group
      of ochratoxigenic strains, frequently isolated from grapes, named A. tubingensis
      like. All strains of A. carbonarius analysed by sequence analysis had identical
      ITS and IGS sequences confirming the lack of significant genetic variability
      within this important ochratoxigenic species.

PMID- 19401262
TI  - Tumor-derived microvesicles modulate the establishment of metastatic melanoma in
      a phosphatidylserine-dependent manner.
AB  - Exposure of phosphatidylserine (PS) on cellular membranes and membrane-derived
      microvesicles stimulates a number of anti-inflammatory responses involved in
      malignant processes. Herein we show that B16F10 cells, a highly metastatic
      melanoma cell line, produce large quantities of PS-containing microvesicles in
      vitro. Tumor microvesicles increased TGF-beta(1) production by cultured
      macrophages and, in vivo, enhanced the metastatic potential of B16F10 cells in
      C57BL/6 mice, both effects being reversed by annexin V. Most strikingly,
      microvesicles induced melanoma metastasis in BALB/c mice, which are normally
      resistant to this tumor cell line. Altogether, this is the first demonstration
      that tumor-derived microvesicles favor the establishment of melanoma metastasis
      in a PS-dependent manner, possibly by down-regulating the host's inflammatory
      and/or anti-tumoral immune responses.

PMID- 19401263
TI  - Cholinergic agonists may produce preservation of myocardial ischaemia/reperfusion
      injury.
AB  - The best treatment for myocardial infarction is to restore blood flow in the
      ischaemic region, though it will bring new myocardial damage known as myocardial
      ischaemia/reperfusion (I/R) injury. Both the ischaemia preconditioning and the
      ischaemia postcondioning have been shown to reduce the myocardial I/R injury, but
      their deficits restrict wide clinical availability. It has been demonstrated that
      inflammation plays a critical role in the I/R injury process. Also plasma levels
      of cytokines and inflammation response can be regulated by specifically
      augmenting cholinergic signaling via the efferent vagus nerve and alpha7 subunit
      containing nicotinic acetylcholine receptor (alpha7nAChR). Because cholinergic
      modalities, acting through vagus nerve- and/or alpha7nAChR-mediated mechanism,
      have been confirmed to suppress excessive inflammation during the I/R injury in
      kidney, liver, lung and intestine, therefore, we hypothesize that cholinergic
      agonists may also provide a protection for the myocardial I/R injury.

PMID- 19401264
TI  - Prevalence of diabetes in patients with schizophrenia in Taiwan: a population
      based National Health Insurance study.
AB  - OBJECTIVE: We conducted this study to investigate the prevalence and correlates
      of diabetes in patients with schizophrenia in Taiwan. METHODS: The National
      Health Research Institute provided a database of 1,000,000 random subjects for
      study. We obtained a random sample aged 18 years and over of 766,427 subjects in
      2005. Those study subjects who had at least one service claim during this year
      for either ambulatory or inpatient care, with a primary diagnosis of
      schizophrenia or with a prescription for treatment of diabetes, were identified.
      RESULTS: The prevalence of diabetes in patients with schizophrenia was higher
      than in the general population (7.90% vs. 5.57%, odds ratio [OR], 1.81; 95%
      confidence interval [CI], 1.61-2.03). Compared with the general population,
      patients with schizophrenia revealed a higher prevalence of diabetes in all age
      groups, except age 70 or more years; among females (10.30% vs. 5.42%, p<0.001),
      and males (5.93% vs. 5.73%, p<0.001); among all insurance amount groups; among
      those living in the northern (7.56% vs. 4.89%, p<0.001), central (8.26% vs.
      5.61%, p<0.001), southern regions (8.45% vs. 6.62%, p<0.001); and among residents
      living in urban (8.18% vs. 5.19%, p<0.001) and rural areas (7.99% vs. 6.15%,
      p<0.001). CONCLUSIONS: Patients with schizophrenia had a much higher prevalence
      of diabetes in younger adult age groups and in females than in the general
      population, a finding that deserves further biological and psychosocial study in
      the future.

PMID- 19401265
TI  - Cost of treatment of schizophrenia in six European countries.
AB  - BACKGROUND AND AIMS: As part of an RCT in six European sites, the direct mental
      health care cost for 422 patients with schizophrenia was analysed according to
      how total and medication costs differed across sites and which variables were
      likely to predict total or service-specific costs. METHOD: Service use was
      recorded continuously during a 12-month follow-up. Prescribed psychotropic
      medication was recorded at baseline and 12 months later. Service use data were
      transformed into EURO, log-transformed and analysed using linear regression
      models. RESULTS: Although samples were homogeneous, large inter-site cost
      differences were found (annual means ranging from 2958 euro in Spain up to 36978
      euro in Switzerland). Psychopharmacologic costs were much more constant across
      sites than costs for other services. Total costs were associated more with region
      or socio-demographic characteristics than with disorder related parameters.
      CONCLUSIONS: The findings confirm remarkable differences in direct costs of
      patients with schizophrenia across Europe. However, the relative stability of
      medication costs suggests a need to analyse mechanisms that influence service
      specific costs for schizophrenia.

PMID- 19401266
TI  - A review of waste management practices and their impact on human health.
AB  - This work reviews (i) the most recent information on waste arisings and waste
      disposal options in the world, in the European Union (EU), in Organisation for
      Economic Co-operation and Development (OEDC) countries, and in some developing
      countries (notably China) and (ii) the potential direct and indirect impact of
      waste management activities on health. Though the main focus is primarily on
      municipal solid waste (MSW), exposure to bioaerosols from composting facilities
      and to pathogens from sewage treatment plants are considered. The reported
      effects of radioactive waste are also briefly reviewed. Hundreds of
      epidemiological studies reported on the incidence of a wide range of possible
      illnesses on employees of waste facilities and on the resident population. The
      main conclusion of the overall assessment of the literature is that the evidence
      of adverse health outcomes for the general population living near landfill sites,
      incinerators, composting facilities and nuclear installations is usually
      insufficient and inconclusive. There is convincing evidence of a high risk of
      gastrointestinal problems associated with pathogens originating at sewage
      treatment plants. In order to improve the quality and usefulness of
      epidemiological studies applied to populations residing in areas where waste
      management facilities are located or planned, preference should be given to
      prospective cohort studies of sufficient statistical power, with access to direct
      human exposure measurements, and supported by data on health effect biomarkers
      and susceptibility biomarkers.

PMID- 19401268
TI  - Enzymatic synthesis of perfluoroalkylated DNA.
AB  - Thymidine analogues 5-trifluoromethyl-, 5-pentafluoroethyl- and 5-(heptafluoro-n
      propyl)-2'-deoxyuridines were synthesised and converted into the corresponding 5'
      triphosphates 1a-c. Performing DNA polymerase-catalyzed primer extension
      reactions these modified nucleotides were incorporated into DNA to create
      perfluoroalkylated nucleic acids. Although single modified nucleotides were
      enzymatically incorporated and further elongated quite similar to the natural
      TTP, the enzymatic synthesis of multi-modified nucleic acids was initial only
      feasible with modifications at every fourth base. Nevertheless, as the effects of
      the modified dUTPs on DNA polymerases varied significantly with the used enzyme,
      Therminator DNA polymerase was proficient in incorporating 11 adjacent 5
      trifluoromethyl-2'-deoxyuridine moieties.

PMID- 19401267
TI  - Childhood delayed septic arthritis of the knee caused by Serratia fonticola.
AB  - We report a first documented case of Serratia fonticola infection in a child with
      septic arthritis, after falling off his bicycle and an infection with hawthorn
      thorns. The aetiologic agent was found to be a S. fonticola strain which was
      first isolated from two synovial fluid samples, only after culture enrichment,
      with failure of DNA amplification. Accurate diagnostic was done, despite S.
      fonticola is often considered as an opportunistic pathogenic bacterium. Alone
      ciprofloxacin treatment was not sufficient to counteract the infection, which was
      eradicated only after surgical drainage performed twice successively, with
      secondary removal of a remaining thorn, and treatment with third generation
      cephalosporin combined with ciprofloxacin for another three months.

PMID- 19401269
TI  - Purification and characterization of rice DNA methyltransferase.
AB  - Epigenetic modification is essential for normal development and plays important
      roles in gene regulation in higher plants. Multiple factors interact to regulate
      the establishment and maintenance of DNA methylation in plant genome. We had
      previously cloned and characterized DNA methyltransferase (DNA MTase) gene
      homologues (OsMET1) from rice. In this present study, determination of DNA MTase
      activity in different cellular compartments showed that DNA MTase was enriched in
      nuclei and the activity was remarkably increased during imbibing dry seeds. We
      had optimized the purification technique for DNA MTase enzyme from shoots of 10
      day-old rice seedlings using the three successive chromatographic columns. The
      Econo-Pac Q, the Hitrap-Heparin and the Superdex-200 columns yielded a protein
      fraction of a specific activity of 29, 298 and 800 purification folds, compared
      to the original nuclear extract, respectively. The purified protein preferred
      hemi-methylated DNA substrate, suggesting the maintenance activity of
      methylation. The native rice DNA MTase was approximately 160-170 kDa and
      exhibited a broad pH optimum in the range of 7.6 and 8.0. The enzyme kinetics and
      inhibitory effects by methyl donor analogs, base analogs, cations, and cationic
      amines on rice DNA MTase were examined. Global cytosine methylation status of
      rice genome during development and in various tissue culture systems were
      monitored and the results suggested that the cytosine methylation level is not
      directly correlated with the DNA MTase activity. The purification and
      characterization of rice DNA MTase enzyme are expected to enhance our
      understanding of this enzyme function and their possible contributions in
      Gramineae plant development.

PMID- 19401270
TI  - Reciprocal regulation of 17beta-estradiol, interleukin-6 and interleukin-8 during
      growth and progression of epithelial ovarian cancer.
AB  - Estrogens have been associated with risk for epithelial ovarian cancer (OVCA).
      Both IL-6 and IL-8 are also likely involved in the progression of OVCA. In order
      to discover the underline molecular mechanism, we investigated the modulation of
      estrogen and two cytokines in the growth and progression of epithelial OVCA. In
      these studies, the effect of 17beta-estradiol (E(2)) on the expression levels of
      IL-6, IL-8 and their receptors was investigated. The effect of IL-6 and IL-8 on
      activation of estrogen-responsive promoter as well as estrogen receptor (ER)alpha
      and ER beta expression was also analyzed. Gene expression profile analysis
      revealed that CAOV-3 and OVCAR-3 cells, which express ER, IL-6 and IL-8
      receptors, are suitable model for this study. We found that E(2) not only
      enhanced IL-6 and IL-8 production via NF-kappaB signaling pathway, but also
      modulated their respective receptor expression. Tamoxifen (Txf), an ER
      antagonist, completely abolished E(2)-stimulated cell growth and the expression
      of IL-6 and IL-8. IL-6/IL-8-induced cell proliferation was completely blocked by
      their specific neutralizing antibodies, which partially inhibited E(2)-induced
      cell growth. In the absence of estrogen, both cytokines activated estrogen
      responsive promoter, which was completely blocked by Txf, and caused a dose
      dependent ER alpha increase and ER beta decrease. Pretreatment of OVCAR-3 with
      p38 MAPK, MEK1/2 or ErbB2 MAPK inhibitors, respectively, blocked IL-6-mediated
      induction of estrogen-responsive promoter while Src inhibitor blocked IL-8
      induced activation of estrogen-responsive promoter. These results provide a novel
      mechanism that estrogens, IL-6 and IL-8 may form a common amplifying signaling
      cascade to modulate OVCA growth and progression. Estrogen-induced OVCA
      proliferation is partially occurring via enhanced IL-6 and IL-8 production and
      modulated their receptors, and IL-6/IL-8 could also promote OVCA growth through
      an ER alpha pathway.

PMID- 19401271
TI  - Reversible parkinsonism with oxcarbazepine use.

PMID- 19401272
TI  - Integration deficiencies associated with continuous limb movement sequences in
      Parkinson's disease.
AB  - The present study examined the extent to which Parkinson's disease (PD)
      influences integration of continuous limb movement sequences. Eight patients with
      idiopathic PD and 8 age-matched normal subjects were instructed to perform
      repetitive sequential aiming movements to specified targets under three-accuracy
      constraints: 1) low accuracy (W = 7 cm) - minimal accuracy constraint, 2) high
      accuracy (W = 0.64 cm) - maximum accuracy constraint, and 3) mixed accuracy
      constraint - one target of high accuracy and another target of low accuracy. The
      characteristic of sequential movements in the low accuracy condition was mostly
      cyclical, whereas in the high accuracy condition it was discrete in both groups.
      When the accuracy constraint was mixed, the sequential movements were executed by
      assembling discrete and cyclical movements in both groups, suggesting that for PD
      patients the capability to combine discrete and cyclical movements to meet a task
      requirement appears to be intact. However, such functional linkage was not as
      pronounced as was in normal subjects. Close examination of movement from the
      mixed accuracy condition revealed marked movement hesitations in the vicinity of
      the large target in PD patients, resulting in a bias toward discrete movement.
      These results suggest that PD patients may have deficits in ongoing planning and
      organizing processes during movement execution when the tasks require to assemble
      various accuracy requirements into more complex movement sequences.

PMID- 19401273
TI  - Gold nanoparticle-modified ultramicroelectrode arrays for biosensing: a
      comparative assessment.
AB  - Gold ultramicroelectrode arrays (UMEAs) modified with gold nanoparticles (GNP)
      are shown to be a highly suitable transducer platform for the fabrication of
      biosensors. Comparative studies were carried out with microelectrodes and UMEAs,
      the latter being either bare or modified with GNPs. GNPs could be
      electrodeposited on to the UMEA surface, thereby increasing its active area up to
      one hundred times but without affecting its inherent electrodic properties.
      Horseradish peroxidase enzyme (HRP) was covalently immobilized over the three
      different transducer platforms by means of a thiol self-assembled monolayer
      (SAM). The resulting biosensors were applied to the amperometric detection of
      catechol, selected as a target analyte, at a set potential of -0.1 V vs. Ag/AgCl.
      The use of GNP-modified UMEAs increased the sensitivity of the developed
      biosensor 3-fold and 80-fold compared with the values achieved with bare UMEA and
      microelectrode based biosensors, respectively. The GNP-modified UMEA based
      biosensor showed a linear response to catechol in the concentration range from
      0.1 mM to 0.4 mM, with a limit of detection of 0.05 mM.

PMID- 19401274
TI  - Management of a case of arhinia.
AB  - Arhinia is a rare condition characterised by the congenital absence of nasal
      structures, with different patterns of presentation, and often associated with
      other craniofacial or somatic anomalies. To date, about 30 surviving cases have
      been reported. We report the case of a female patient aged 6 years, who underwent
      internal and external nose reconstruction using a staged procedure: a nasal
      airway was obtained through maxillary osteotomy and ostectomy, and lined with a
      local skin flap and split-thickness skin grafts; then the external nose was
      reconstructed with an expanded frontal flap, armed with an autogenous rib
      framework.

PMID- 19401275
TI  - The effect of Hirudoid on random skin-flap survival in rats.
AB  - BACKGROUND: One of the main fields of research in flap surgery is to increase the
      viability of flaps. Many materials have been tested for this purpose. This study
      shows that topical application of Hirudoid, an organoheparinoid, increases flap
      survival of dorsal flaps in rats. METHODS: Hirudoid was used topically every day
      in eight of 16 rats in which 10x3-cm dorsal flaps were prepared. The flaps were
      taken for analysis on the 10th day. Analysis of the flaps was performed using
      digital measurement and scintigraphy. RESULTS: Analysis revealed that the flap
      necrosis area was smaller in the Hirudoid group compared to the control group. In
      addition, the area exhibiting radioactive uptake in scintigraphy was greater in
      the treatment group. CONCLUSION: Topical administration of Hirudoid may
      significantly improve flap survival.

PMID- 19401276
TI  - Secondary syphilis with progressive ocular involvement in an immunocompetent
      patient.

PMID- 19401277
TI  - Diagnosis of dermatological and systemic diseases.

PMID- 19401278
TI  - Television viewing and other screen-based entertainment in relation to multiple
      socioeconomic status indicators and area deprivation: the Scottish Health Survey
      2003.
AB  - BACKGROUND: Sedentary behaviour (sitting) is detrimental to health, independently
      of participation in physical activity. Socioeconomic position (SEP) is known to
      relate strongly to physical activity participation but we know very little about
      how SEP relates to sedentary behaviour. This study aimed to assess the
      relationships between SEP, neighbourhood deprivation and an index of sedentary
      time. METHODS: Cross-sectional study of a representative sample of 7940 Scottish
      adults who participated in the 2003 Scottish Health Survey, which collected
      information on SEP (household income, social class and education), neighbourhood
      deprivation (Scottish Index of Multiple Deprivation), television and other screen
      based entertainment time, and physical activity. RESULTS: The three indicators of
      SEP and deprivation index were independently of each other associated with daily
      times of television and other screen-based entertainment, even after adjustment
      for occupational and leisure-time physical activity, health status, smoking,
      alcohol drinking, car ownership and body mass index: income p = 0.002; social
      class p<0.001; education p<0.001, deprivation p<0.001. Also, there was a strong
      cumulative effect of SEP (a composite scale where 0 = lowest, 9 = highest SEP
      position) with those in the lowest SEP spending an additional 109 minutes each
      day on screen-based entertainment compared to those in the highest socioeconomic
      position (p<0.001 for linear trend). CONCLUSION: Adverse socioeconomic position
      is associated with a cumulative increase in the time spent on screen-based
      entertainment. Reducing inequalities would be expected to reduce exposure to
      sedentary behaviours, such as excessive screen-based entertainment times, and
      therefore reduce the risk of chronic disease.

PMID- 19401279
TI  - Susceptibility variants for rheumatoid arthritis in the TRAF1-C5 and 6q23 loci: a
      meta-analysis.
AB  - BACKGROUND: Genome-wide association studies have proposed susceptibility variants
      for rheumatoid arthritis in the TRAF1-C5 locus and 6q23 region. Furthermore,
      additional independent studies have investigated the same or highly linked
      polymorphisms in the same regions. OBJECTIVE: To carry out a meta-analysis of the
      available evidence for the association of polymorphisms in the TRAF1-C5 locus and
      6q23 region with rheumatoid arthritis. METHODS: Data were synthesised for four
      polymorphisms: rs3761847 (n=13 datasets) and rs2900180 (n=9 datasets) in the
      TRAF1-C5 locus, and rs10499194 (n=5 datasets) and rs6920220 (n=7 datasets) in the
      6q23 region. Meta-analyses for subgroups defined by anti-cyclic citrullinated
      peptide (anti-CCP) and rheumatoid factor (RF) status were also performed.
      RESULTS: The polymorphism rs6920220 reached genome-wide statistical significance
      with p=7.9 x 10(-17) and an allelic odds ratio of 1.24 (95% CI 1.18 to 1.30) and
      no between-study heterogeneity (I(2)=0%). The risk was significantly stronger in
      patients with anti-CCP antibodies and in patients with RF. The other three
      variants showed large between-study heterogeneity across datasets (I(2) range 74
      82%); rs10499194 was nominally statistically significant after exclusion of the
      discovery data. Two variants had genome-wide statistical significance in
      subgroups defined by the presence of RF (rs3761847 and rs6920220) or anti-CCP
      (rs6920220). CONCLUSIONS: Genetic markers in the 6q23 region and TRAF1-C5 are
      associated with rheumatoid arthritis, in particular with positive anti-CCP and RF
      profile. With the exception of rs6920220, which shows highly consistent results,
      other proposed markers have high between-study heterogeneity that may reflect
      unrecognised phenotypic or genetic variability (eg, gene environment
      interactions) within rheumatoid arthritis. Furthermore, these markers may not be
      the true causative loci but rather be in linkage disequilibrium with the true
      ones.

PMID- 19401280
TI  - Cardiorenal syndrome in decompensated heart failure.
AB  - Worsening renal function during treatment of acute decompensated heart failure
      (ADHF) often complicates the treatment course of heart failure. Furthermore, the
      development of worsening renal function is a strong independent predictor of long
      term adverse outcomes. Sometimes referred to as 'cardiorenal syndrome,' the
      definition varies widely, and the overall understanding of pathogenesis is
      limited. This is probably owing to the lack of precision and characterisation of
      renal compromise during treatment of heart failure. Traditionally, the
      predominant cause has been attributed to impairment of cardiac output and
      relative underfilling of arterial perfusion. Emerging data have led to a
      resurgence of interest in the importance of venous congestion and elevated intra
      abdominal pressure rather than confining it to impaired forward cardiac output as
      the primary driver of renal impairment. These revived concepts may support the
      role of novel renal-sparing approaches to salt and water removal and renal
      preservation, but better ways to distinguish haemodynamic versus other
      nephrotoxic aetiologies are needed.

PMID- 19401281
TI  - RAAS inhibition/blockade in patients with cardiovascular disease: implications of
      recent large-scale randomised trials for clinical practice.

PMID- 19401282
TI  - Intracoronary optical coherence tomography assessment of spontaneous coronary
      artery dissection.

PMID- 19401283
TI  - NICE guideline on acute stroke and TIA: commentary.

PMID- 19401284
TI  - Statins: established indications and controversial subgroups.

PMID- 19401285
TI  - Blood pressure changes and survival in chronic heart failure.

PMID- 19401286
TI  - Drug-eluting stents for the treatment of coronary artery disease: NICE technology
      appraisal guidance.

PMID- 19401287
TI  - Observations on 35 years as an expert witness in American malpractice litigation:
      a comparison with the British legal system.

PMID- 19401288
TI  - Effective platelet inhibition by aspirin and clopidogrel: where are we now?

PMID- 19401289
TI  - Is there evidence of vertical transmission of variant Creutzfeldt-Jakob disease?
AB  - OBJECTIVES: The possibility of vertical transmission of variant Creutzfeldt-Jakob
      disease (vCJD) has been raised because of the widespread distribution of
      infectivity in vCJD and the demonstration that this condition can be transmitted
      through blood transfusion. The aim of this study is to search for evidence of
      this type of transmission of vCJD. METHODS: A national surveillance system for
      CJD has been established in the UK since 1990. Through this register, details
      were extracted of all children born to vCJD cases up to March 2009. This list was
      checked against the CJD register and cases identified through the UK study of
      Progressive Intellectual and Neurological Deterioration in children to determine
      whether any of the children of vCJD cases had themselves developed a progressive
      neurological disorder or vCJD. RESULTS: 125 children were born to parents with a
      diagnosis of vCJD. Nine of these children were born to females with vCJD who were
      symptomatic at conception, birth or within a year of clinical onset. Only one
      woman was known to have breast fed her child. None of the children of vCJD cases
      have been referred to the National CJD Surveillance Unit as suspected vCJD and
      none have been classified as suffering from a progressive neurodegenerative
      disorder through the Progressive Intellectual and Neurological Deterioration
      study. One of the children has been investigated by the National Prion Unit (see
      accompanying case report). INTERPRETATION: To date there is no evidence of
      vertical transmission of vCJD. However, the incubation period through this
      mechanism might be prolonged and it will be many years before observational data
      can exclude this possibility.

PMID- 19401290
TI  - Trends in Medicaid physician fees, 2003-2008.
AB  - Medicaid physician fees increased 15.1 percent, on average, between 2003 and
      2008. This was below the general rate of inflation, resulting in a reduction in
      real fees. Only primary care fees grew at the rate of inflation-20 percent
      between 2003 and 2008. However, because of slow growth in Medicare fees, Medicaid
      fees closed a small portion of their ongoing gap relative to Medicare-growing
      from 69 percent to 72 percent of Medicare. The increase in Medicaid fees relative
      to Medicare fees resulted from relative increases for primary care and
      obstetrical services, but not for other services.

PMID- 19401291
TI  - Uptake of aluminium into Arabidopsis root cells measured by fluorescent lifetime
      imaging.
AB  - BACKGROUND AND AIMS: Measuring the Al(3+) uptake rate across the plasma membrane
      of intact root cells is crucial for understanding the mechanisms and time-course
      of Al toxicity in plants. However, a reliable method with the sufficient spatial
      and temporal resolution to estimate Al(3+) uptake in intact root cells does not
      exist. METHODS: In the current study, fluorescent lifetime imaging (FLIM)
      analysis was used to quantify Al(3+) uptake in the root-cell cytoplasm in vivo.
      This was performed via the estimation of the fluorescence lifetime of Al
      lumogallion {5-chloro-3[(2,4-dihydroxyphenyl)azo]-2-hydroxybenzenesulfonic acid}
      complexes and measurements of intracellular pH while exposing arabidopsis
      seedlings to acidic and Al(3+) stresses. KEY RESULTS: The lifetime of Al
      lumogallion complexes fluorescence is pH-dependent. The primary sites for Al(3+)
      entry are the meristem and distal elongation zones, while Al(3+) uptake via the
      cortex and epidermis of the mature root zone is limited. The maximum rates of Al
      uptake into the cytoplasm (2-3 micromol m(-3) min(-1) for the meristematic root
      zone and 3-7 micromol m(-3) min(-1) for the mature zone) were observed after a 30
      min exposure to 100 microM AlCl(3) (pH 4.2). Intracellular Al concentration
      increased to 0.4 microM Al within the first 3 h of exposure to 100 microM
      AlCl(3). CONCLUSIONS: FLIM analysis of the fluorescence of Al-lumogallion
      complexes can be used to reliably quantify Al uptake in the cytoplasm of intact
      root cells at the initial stages of Al(3+) stress.

PMID- 19401292
TI  - Ageing effects in an iteroparous plant species with a variable life span.
AB  - BACKGROUND AND AIMS: Ageing effects may be due to dysfunction leading to
      decreasing reproduction and survival with age. In plants, however, other
      (physiological) causes, associated with size for example, may also play a role.
      Iteroparous plants with genetically variable life spans can be helpful in
      unravelling these two aspects of changes associated with growing older. METHODS:
      In a long-term experiment, Beta vulgaris ssp. maritima (sea beet) plants from the
      same set of populations but with different ages were compared for flowering date
      over several years. Flowering date, root growth and seed production were measured
      in a synthetic population and in progenies derived from reciprocal crosses over
      three consecutive years and analysed with respect to the number of years yet to
      live. Heritabilities of these three characters and of life span were estimated.
      KEY RESULTS: Flowering occurred on average 1.3 d later each year over a plant's
      whole lifetime. In the year before dying, plants flowered on average 3.3 d later
      and both root investment and seed production decreased significantly compared
      with plants that remained alive for at least 1 further year. The negative
      relationship (trade-off) between reproduction and root investment in early life
      became positive near the end of life, and the positive relationship between
      flowering date and root growth became negative. CONCLUSIONS: Effects of ageing-
      in the sense of a decline in reproduction and root storage--combined with later
      flowering were particularly pronounced in the year before death. The gradual
      change in flowering phenology, observed over the whole lifetime, could have a
      physiological basis unrelated to dysfunction.

PMID- 19401293
TI  - Reimplantation valve-sparing aortic root replacement with the Valsalva graft:
      what have we learnt after 100 cases?
AB  - OBJECTIVES: Reimplantation valve-sparing aortic root replacement has been
      increasingly performed with improving perioperative and mid-term results. The
      success of this operation primarily depends on preserving the highly
      sophisticated dynamic function of the aortic valve by recreating an anatomical
      three-dimensional configuration similar to the normal aortic root, thus
      minimizing the mechanical stress and strain on the cusps. Over the years several
      techniques have been proposed to reproduce the sinuses of Valsalva. We reviewed
      our experience with aortic valve reimplantation by means of a modified Dacron
      graft that incorporates sinuses of Valsalva, in a series of 100 consecutive
      patients. METHODS: During a 60-month period, 100 patients with aortic root
      aneurysm underwent aortic valve reimplantation using the Gelweave Valsalva
      prosthesis. There were 74 males and the mean age was 60+/-12 years (range 28-83
      years). Five patients had the Marfan's syndrome, 15 had a bicuspid aortic valve.
      Cusp repair was performed in five patients. The mean follow-up time was 28.6
      months (range 1-60). Transesophageal echocardiogram was performed at the end of
      each procedure to assess the aortic valve in terms of competence, dynamic motion
      and level of coaptation within the graft. RESULTS: There was one hospital death
      and two late deaths. Overall survival at 60 months was 91.7+/-5.1%. Five patients
      developed severe aortic incompetence (AI) during follow-up requiring aortic valve
      replacement (AVR). The 60 months freedom from re-operation due to AI was 90.9+/
      4.4%. One patient had moderate AI at latest echocardiographic study. The 60
      months freedom from AI>2+ was 91.6+/-7.9%. Cox regression identified cusp's
      repair as independent risk factor (P=0.001) for late reimplantation failure (AVR
      or AI>2+). There were no episodes of endocarditis and the majority of the
      patients (88%) were in New York Heart Association functional class I.
      CONCLUSIONS: The aortic valve reimplantation with the Gelweave Valsalva
      prosthesis provided satisfactory mid-term results. An accurate assessment of the
      level of coaptation of the aortic cusps in respect to the lower rim of the Dacron
      graft by means of intraoperative transesophageal echocardiogram at the end of
      each procedure is mandatory in order to avoid early reimplantation failure.
      Cusp's repair may play an important role in the development of late AI. However,
      long-term results are needed in order to define the durability of this technique.

PMID- 19401294
TI  - Extended videoscopic robotic thymectomy with the da Vinci telemanipulator for the
      treatment of myasthenia gravis: the Vienna experience.
AB  - Surgical treatment of myasthenia gravis should include the complete resection of
      the thymus with the whole fatty tissue adherent to the pericardium for
      immunologic as well as oncologic reasons. The aim of the current study was to
      investigate the efficacy and safety of robotic approach. A total of 18 patients
      with myasthenia gravis (mean age 44 years) have been operated robotically via a
      left-sided approach. Preoperative MGFA (Myasthenia Gravis Foundation of America)
      classification was: Class I n=4, Class IIa n=4, Class IIb n=5, and Class IIIa
      n=3, IIIb n=2. Total endoscopic resection was feasible in 17/18 patients. One
      patient had to be converted due to bleeding. In the remaining patients, operative
      time was 175 min, intensive care unit (ICU) one day, hospital stay four days. In
      all patients it was possible to perform an extended thymic resection. MGFA post
      intervention status after a mean of 18 months follow-up showed complete stable
      remission n=5, pharmacologic remission n=4, minimal manifestations n=5, unchanged
      n=1. Complete endoscopic thymus surgery with the da Vinci surgical system enables
      a complete and extended resection of all thymic tissue in the mediastinum. Due to
      the minimal trauma, patients can return to full activity within a short time.

PMID- 19401295
TI  - Prognostic significance of pleural lavage cytology after thoracotomy and before
      closure of the chest in lung cancer.
AB  - Some reports have described pleural lavage cytology (PLC) to be a prognostic
      factor for non-small cell lung cancer (NSCLC) patients. However, there have only
      been a few reports describing the findings both immediately after thoracotomy
      (PLC after thoracotomy) and before the closure of the chest (PLC before closure).
      From April 2002 to April 2008, both PLC after thoracotomy and PLC before closure
      were performed in 296 consecutive patients who underwent resections for NSCLC.
      PLC after thoracotomy was positive in 14 patients. The survival rate in the PLC
      after thoracotomy positive cases was significantly poorer than in PLC after
      thoracotomy negative cases (P=0.047). In contrast, there were 26 PLC before
      closure positive cases. The survival rate in the PLC before closure positive
      cases was significantly poorer than in the PLC before closure negative cases
      (P<0.0001). Multivariate analyses revealed that PLC after thoracotomy is not an
      independent prognostic factor in our study. However, PLC before closure was an
      independent prognostic factor based on multivariate analyses. We conclude that
      PLC before closure was found to be a better prognostic factor than PLC after
      thoracotomy for NSCLC patients.

PMID- 19401297
TI  - Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis
      accompanied by dysregulated planar cell polarity and canonical Wnt signaling
      pathways.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is characterized by large
      fluid-filled cysts and progressive deterioration of renal function necessitating
      renal replacement therapy. Previously, we generated a tamoxifen-inducible, kidney
      epithelium-specific Pkd1-deletion mouse model and showed that inactivation of the
      Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of
      disease in adult mice. Therefore, we hypothesized that injury-induced tubular
      epithelial cell proliferation may accelerate cyst formation in the kidneys of
      adult Pkd1-deletion mice. Mice were treated with the nephrotoxicant 1,2
      dichlorovinyl-cysteine (DCVC) after Pkd1-gene inactivation, which indeed
      accelerated cyst formation significantly. After the increased proliferation
      during tissue regeneration, proliferation decreased to basal levels in Pkd1
      deletion mice just as in DCVC-treated controls. However, in severe cystic
      kidneys, 10-14 weeks after injury, proliferation increased again. This biphasic
      response suggests that unrestricted cell proliferation after injury is not the
      underlying mechanism for cyst formation. Aberrant planar cell polarity (PCP)
      signaling and increased canonical Wnt signaling are suggested to be involved in
      cyst formation. Indeed, we show here that in Pkd1 conditional deletion mice
      expression of the PCP component Four-jointed (Fjx1) is decreased while its
      expression is required during tissue regeneration. In addition, we show that
      altered centrosome position and the activation of canonical Wnt signaling are
      early effects of Pkd1-gene disruption. This suggests that additional stimuli or
      events are required to trigger the process of cyst formation. We propose that
      during tissue repair, the integrity of the newly formed Pkd1-deficient cells is
      modified rendering them susceptible to subsequent cyst formation.

PMID- 19401296
TI  - Matrix metalloproteinase-9 inhibition ameliorates pathogenesis and improves
      skeletal muscle regeneration in muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disorder of
      skeletal muscle caused by mutation in dystrophin gene. Although the degradation
      of skeletal muscle extracellular matrix, inflammation and fibrosis are the common
      pathological features in DMD, the underlying mechanisms remain poorly understood.
      In this study, we have investigated the role and the mechanisms by which
      increased levels of matrix metalloproteinase-9 (MMP-9) protein causes myopathy in
      dystrophin-deficient mdx mice. The levels of MMP-9 but not tissue inhibitor of
      MMPs were drastically increased in skeletal muscle of mdx mice. Besides skeletal
      muscle, infiltrating macrophages were found to contribute significantly to the
      elevated levels of MMP-9 in dystrophic muscle. In vivo administration of a
      nuclear factor-kappa B inhibitory peptide, NBD, blocked the expression of MMP-9
      in dystrophic muscle of mdx mice. Deletion of Mmp9 gene in mdx mice improved
      skeletal muscle structure and functions and reduced muscle injury, inflammation
      and fiber necrosis. Inhibition of MMP-9 increased the levels of cytoskeletal
      protein beta-dystroglycan and neural nitric oxide synthase and reduced the
      amounts of caveolin-3 and transforming growth factor-beta in myofibers of mdx
      mice. Genetic ablation of MMP-9 significantly augmented the skeletal muscle
      regeneration in mdx mice. Finally, pharmacological inhibition of MMP-9 activity
      also ameliorated skeletal muscle pathogenesis and enhanced myofiber regeneration
      in mdx mice. Collectively, our study suggests that the increased production of
      MMP-9 exacerbates dystrophinopathy and MMP-9 represents as one of the most
      promising therapeutic targets for the prevention of disease progression in DMD.

PMID- 19401300
TI  - Longitudinal 2D strain at rest predicts the presence of left main and three
      vessel coronary artery disease in patients without regional wall motion
      abnormality.
AB  - AIMS: Non-invasive echocardiographic detection of coronary artery disease (CAD),
      even in left main or three-vessel CAD, usually requires a stress test since
      regional wall motion abnormalities (RWMA) are not always evident at rest. Strain
      is a more sensitive parameter of myocardial systolic function and may be abnormal
      in patients with severe CAD. METHODS AND RESULTS: We evaluated whether peak
      systolic longitudinal strain (PSLS) of left ventricle using 2D speckle tracking
      method might be useful for screening of severe CAD. One hundred and eight
      patients who underwent echocardiography and coronary angiography were evaluated.
      Patients were grouped according to the coronary angiographic findings as follows;
      high-risk group with left main or three-vessel CAD (n = 38), low-risk group with
      one- or two-vessel CAD (n = 28), and control group without CAD (n = 30). PSLSs of
      all left ventricular segments were obtained successfully in 96 (89%) patients.
      None had RWMA at resting echocardiogram. PSLS was significantly reduced,
      especially in mid- and basal segments, in the high-risk group. Receiver operating
      characteristic (ROC) curve analysis demonstrated that mid- and basal PSLSs could
      effectively detect patients with severe CAD (area under ROC curve = 0.83, 95% CI
      0.75-0.91). According to ROC curve analysis, -17.9% appears to be a helpful
      cutoff value for discriminating those with severe CAD (specificity 79% and
      sensitivity 79%). CONCLUSION: PSLS at rest was significantly lower in patients
      with left main or three-vessel CAD without RWMA, and might be useful for
      identifying patients with a severe CAD.

PMID- 19401299
TI  - Tissue velocities, strain, and strain rate for echocardiographic assessment of
      ventricular function in congenital heart disease.
AB  - During the last decade tissue Doppler and myocardial deformation imaging has been
      introduced to quantify myocardial function in patients with congenital heart
      disease. These methods could have potential benefits for patients where the
      anatomy makes it difficult to quantify ventricular function using M-mode or two
      dimensional volumetric techniques. In this overview, the potential benefits as
      well as limitations of the techniques are discussed. Looking directly into the
      myocardium renders the techniques geometry-independent, allowing the
      quantification of right ventricular as well as univentricular systolic function.
      The limitations include the influence of variable loading conditions as well as
      different methodological problems.

PMID- 19401298
TI  - Inhibition of RhoA pathway rescues the endocytosis defects in Oligophrenin1 mouse
      model of mental retardation.
AB  - The patho-physiological hypothesis of mental retardation caused by the deficiency
      of the RhoGAP Oligophrenin1 (OPHN1), relies on the well-known functions of Rho
      GTPases on neuronal morphology, i.e. dendritic spine structure. Here, we describe
      a new function of this Bin/Amphiphysin/Rvs domain containing protein in the
      control of clathrin-mediated endocytosis (CME). Through interactions with Src
      homology 3 domain containing proteins involved in CME, OPHN1 is concentrated to
      endocytic sites where it down-regulates the RhoA/ROCK signaling pathway and
      represses the inhibitory function of ROCK on endocytosis. Indeed disruption of
      Ophn1 in mice reduces the endocytosis of synaptic vesicles and the post-synaptic
      alpha-amino-3-hydroxy-5-methylisoazol-4-propionate (AMPA) receptor
      internalization, resulting in almost a complete loss of long-term depression in
      the hippocampus. Finally, pharmacological inhibition of this pathway by ROCK
      inhibitors fully rescued not only the CME deficit in OPHN1 null cells but also
      synaptic plasticity in the hippocampus from Ophn1 null model. Altogether, we
      uncovered a new patho-physiological mechanism for intellectual disabilities
      associated to mutations in RhoGTPases linked genes and also opened new directions
      for therapeutic approaches of congenital mental retardation.

PMID- 19401301
TI  - Reduced contractile reserve of the systemic right ventricle under Dobutamine
      stress is associated with increased brain natriuretic peptide levels in patients
      with complete transposition after atrial repair.
AB  - AIMS: To compare B-type natriuretic peptide (BNP) levels with response of
      systemic right ventricular function to Dobutamine stress. METHODS AND RESULTS:
      Sixteen patients aged 25.6 +/- 3.7 years (eight each after Senning or Mustard
      repair of complete transposition) were studied. Transoesophageal imaging was
      performed in the catheterization laboratory under general anaesthesia before and
      at the end of a 10 min infusion of 5 microg/kg/min of Dobutamine. The BNP levels
      were measured at rest. Myocardial Doppler data were acquired before and at peak
      stress in a four-chamber view. The BNP (pg/mL) values of 67.3 +/- 47.5 (14-189)
      were elevated. There was no correlation between BNP and IVA, strain, or systolic
      and diastolic velocities at rest. Dobutamine stress led to a significant increase
      in IVA, s-velocity, and strain but no significant change in e-velocity. A
      correlation was found between increase in IVA under Dobutamine and BNP levels (r
      = 0.57, P < 0.02). CONCLUSION: Elevated BNP levels correlate with response of
      systolic right ventricular function assessed by IVA to Dobutamine stress.

PMID- 19401303
TI  - A competition-based assay for the screening of species-specific antibiotics.
AB  - OBJECTIVES: To develop a high throughput screening-compatible assay for the
      selection of species-specific antibiotics that do not harm human cells. METHODS:
      Staphylococcus aureus and human reporter cells continuously generating a
      fluorescence signal were competitively co-cultivated. The fluorescence signals
      were determined in the presence and absence of the specific antibiotic
      streptomycin and the toxic compound sodium azide. The results were compared with
      a standard cfu assay. RESULTS: In the absence of an effective antibiotic, S.
      aureus outgrew the human reporter cells and thus abolished the fluorescence
      signal. Conversely, the addition of streptomycin resulted in the growth of the
      reporter cells and a strong fluorescence signal. When sodium azide was added
      instead of streptomycin, only a very low background signal was obtained
      indicating toxicity and damage to the human reporter cells. The assay proved to
      be highly reliable (Z-factor >0.9) and high fluorescence signals correctly
      correlated with the efficient inhibition of S. aureus, as determined in
      comparative cfu assays. CONCLUSIONS: In contrast to conventional cfu assays, the
      co-cultivation system allows the effects of a drug candidate on pathogens and
      human cells to be monitored simultaneously. Cytotoxic compounds can, therefore,
      be quickly ruled out during a primary screen. The nature of the screen also
      enables effective antibiotics to be identified without engineering the target
      pathogen to yield a fluorescence signal.

PMID- 19401302
TI  - Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved
      post-ischaemic recovery of heart contractile function.
AB  - AIMS: This study examined the functional role of B-type natriuretic peptide (BNP)
      in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted
      disruption of the sEH or Ephx2 gene (sEH null). METHODS AND RESULTS: Isolated
      mouse hearts were perfused in the Langendorff mode and subjected to global no
      flow ischaemia followed by reperfusion. Hearts were analysed for recovery of left
      ventricular developed pressure (LVDP), mRNA levels, and protein expression. Naive
      hearts from sEH null mice had similar expression of preproBNP (Nppb) mRNA
      compared with wild-type (WT) hearts. However, significant increases in Nppb mRNA
      and BNP protein expression occurred during post-ischaemic reperfusion and
      correlated with improved post-ischaemic recovery of LVDP. Perfusion with the
      putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid prior to
      ischaemia reduced the preproBNP mRNA in sEH null hearts. Inhibitor studies
      demonstrated that perfusion with the natriuretic peptide receptor type-A (NPR-A)
      antagonist, A71915, limited the improved recovery in recombinant full-length
      mouse BNP (rBNP)- and 11,12-EET-perfused hearts as well as in sEH null mice.
      Increased expression of phosphorylated protein kinase C epsilon and Akt were
      found in WT hearts perfused with either 11,12-EET or rBNP, while mitochondrial
      glycogen synthase kinase-3beta was significantly lower in the same samples.
      Furthermore, treatment with the phosphoinositide 3-kinase (PI3K) inhibitor
      wortmannin abolished improved LVDP recovery in 11,12-EET-treated hearts but not
      did significantly inhibit recovery of rBNP-treated hearts. CONCLUSION: Taken
      together, these data indicate that EET-mediated cardioprotection involves BNP and
      PI3K signalling events.

PMID- 19401304
TI  - Outcomes of early switching from intravenous to oral antibiotics on medical
      wards.
AB  - OBJECTIVES: To evaluate outcomes following implementation of a checklist with
      criteria for switching from intravenous (iv) to oral antibiotics on unselected
      patients on two general medical wards. METHODS: During a 12 month intervention
      study, a printed checklist of criteria for switching on the third day of iv
      treatment was placed in the medical charts. The decision to switch was left to
      the discretion of the attending physician. Outcome parameters of a 4 month
      control phase before intervention were compared with the equivalent 4 month
      period during the intervention phase to control for seasonal confounding (before
      after study; April to July of 2006 and 2007, respectively): 250 episodes (215
      patients) during the intervention period were compared with the control group of
      176 episodes (162 patients). The main outcome measure was the duration of iv
      therapy. Additionally, safety, adherence to the checklist, reasons against
      switching patients and antibiotic cost were analysed during the whole year of the
      intervention (n = 698 episodes). RESULTS: In 38% (246/646) of episodes of
      continued iv antibiotic therapy, patients met all criteria for switching to oral
      antibiotics on the third day, and 151/246 (61.4%) were switched. The number of
      days of iv antibiotic treatment were reduced by 19% (95% confidence interval 9%
      29%, P = 0.001; 6.0-5.0 days in median) with no increase in complications. The
      main reasons against switching were persisting fever (41%, n = 187) and absence
      of clinical improvement (41%, n = 185). CONCLUSIONS: On general medical wards, a
      checklist with bedside criteria for switching to oral antibiotics can shorten the
      duration of iv therapy without any negative effect on treatment outcome. The
      criteria were successfully applied to all patients on the wards, independently of
      the indication (empirical or directed treatment), the type of (presumed)
      infection, the underlying disease or the group of antibiotics being used.

PMID- 19401305
TI  - Blepharoptosis following oxaliplatin administration.
AB  - Oxaliplatin is a unique platinum derivative with anti-tumor activity in a number
      of malignancies, with neurotoxicity being a frequent side effect. Neurotoxicity
      can manifest in an acute phase and a chronic phase. The acute phase usually
      presents as dysesthesias of the hands and feet, jaw tightness, and
      pharyngolaryngo-dysesthesia, triggered and exacerbated by physical contact with
      cold temperatures. Although various other symptoms have been reported in the
      literature, little details are available. We report here, in detail, a case of
      blepharoptosis which appeared after repeated oxaliplatin infusions, and the
      disappearance of which seemed to be dependent on the infusion rate.

PMID- 19401307
TI  - Retrospective evaluation of venous thromboembolism prophylaxis in the adult
      cancer population.
AB  - STUDY OBJECTIVES: Hospitalized cancer patients are at an increased risk for
      venous thromboembolism (VTE) and it is recommended they receive pharmacologic
      prophylaxis unless otherwise contraindicated. The majority of data supporting
      this recommendation comes from sub-group analyses and extrapolation of data
      gathered in general medical/surgical patients. This study seeks to assess the
      safety and efficacy of VTE prophylaxis in cancer patients admitted to our
      institution. METHODS: Charts of patients 18-89 years of age receiving VTE
      prophylaxis with unfractionated heparin, low molecular weigh heparin, or
      fondaparinux while admitted to Karmanos Cancer Center between September and
      October 2007 were retrospectively reviewed. Risk factors for VTE were assessed
      and the efficacy/safety of the prophylactic agents was compared. RESULTS: One
      hundred and eighty consecutive patients were identified. The average number of
      risk factors for developing VTE was 3-4 per hospital admission in addition to an
      active cancer diagnosis. Three VTEs occurred in the heparin group with two
      patients experiencing a VTE during their admission and one experiencing a VTE
      within 1 month after discharge. Four (2.6%) patients receiving heparin had a
      major bleeding event. Minor bleeding occurred in 14.3, 11.5, and 22.2% of
      patients receiving heparin, enoxaparin, and fondaparinux, respectively.
      CONCLUSIONS: This retrospective study showed cancer patients are at increased
      risk for VTE, typically with 3-4 risk factors per admission. VTEs were uncommon;
      however, three patients receiving heparin experienced a VTE and four had a major
      bleeding event. Minor bleeding rates were similar among groups.

PMID- 19401306
TI  - Clinical significance of ABCB1 genotyping in oncology.
AB  - BACKGROUND: P-glycoprotein (Pgp) is a drug efflux pump that transports natural
      products, including taxanes and other chemotherapeutic agents, from cells.
      Several frequent polymorphisms in ATP binding cassette gene B1 (ABCB1) may
      influence Pgp levels and drug efflux. The purpose of this review was to assess
      the clinical significance of ABCB1 polymorphisms in oncology. METHODS: Peer
      reviewed studies were identified through a search of PubMed/MEDLINE (1990-2008)
      and the ASCO abstracts (2003-2008) database. Included studies described clinical
      trials where ABCB1 genotyping was performed in patients with cancer. Search terms
      included ABCB1, Pgp, docetaxel, paclitaxel, irinotecan, imatinib, and anticancer
      agent. Studies were excluded if the manuscript was not available in English.
      RESULTS: The influence of polymorphisms in ABCB1 2677G>T/A, 3435C>T, and 1236C>T
      and progression-free and overall survival in 309 patients from the Australian
      Ovarian Cancer Study treated with paclitaxel/carboplatin demonstrated that
      compared to homozygote GG carriers at 2677, women with the minor T/A alleles were
      significantly less likely to relapse following treatment. Other trials of ABCB1
      genotyping in breast and prostate cancer patients receiving taxanes have shown
      inconsistent results. Pharmacokinetic studies where ABCB1 was genotyped and
      patients received irinotecan or imatinib have also shown inconsistent results.
      CONCLUSION: A number of commercially available drugs are substrates for Pgp, and
      the ABCB1-variant genotypes are frequent and functionally significant, which may
      have future implications for drug dosing.

PMID- 19401308
TI  - The role of the pharmacist in optimizing the use of erythropoietin stimulating
      agents.
AB  - PURPOSE: With the emerging new warnings surrounding the use of erythropoiesis
      stimulating agents (ESAs), the pharmacist's role as health educator and risk
      communicator expands further to include patient scrutiny to check for eligibility
      and patient monitoring to check for response or toxicity. This review explores
      the benefits and risks linked to ESAs use, and the proposed role. SUMMARY: ESAs
      have been increasingly used for the treatment of chemotherapy-induced anemia
      because of its documented effect on decreasing transfusion dependency. However,
      their use has been associated with thromboembolic complications, tumor
      progression, and decreased overall survival. This review covers current
      recommendations and guidelines that surround ESAs use in the supportive care of
      cancer patients. CONCLUSION: To minimize or prevent the complications associated
      with ESAs use, cancer patients should be adequately monitored and counseled. This
      highlights the importance of the pharmacist's involvement to optimize patient
      care.

PMID- 19401309
TI  - Measurements of the wall shear stress distribution in the outflow tract of an
      embryonic chicken heart.
AB  - In order to study the role of blood-tissue interaction in the developing chicken
      embryo heart, detailed information about the haemodynamic forces is needed. In
      this study, we present the first in vivo measurements of the three-dimensional
      distribution of wall shear stress (WSS) in the outflow tract (OFT) of an
      embryonic chicken heart. The data are obtained in a two-step process: first, the
      three-dimensional flow fields are measured during the cardiac cycle using
      scanning microscopic particle image velocimetry; second, the location of the wall
      and the WSS are determined by post-processing flow velocity data (finding
      velocity gradients at locations where the flow approaches zero). The results are
      a three-dimensional reconstruction of the geometry, with a spatial resolution of
      15-20 microm, and provides detailed information about the WSS in the OFT. The
      most significant error is the location of the wall, which results in an estimate
      of the uncertainty in the WSS values of 20 per cent.

PMID- 19401314
TI  - Performance of rapid diagnostic tests for malaria varies widely.

PMID- 19401315
TI  - FDA agrees to ease restrictions on emergency contraceptive.

PMID- 19401319
TI  - WHO raises level of alert on flu pandemic.

PMID- 19401320
TI  - Cardiac resynchronisation therapy for chronic heart failure and conduction delay.

PMID- 19401321
TI  - Doxycycline causes regression of endometriotic implants: a rat model.
AB  - BACKGROUND: Doxycycline (Dox) has a number of non-antibiotic properties. One of
      them is the inhibition of matrix metalloproteinase (MMP) activity. The aim of
      this study was to assess the effects of Dox in a rat endometriosis model.
      METHODS: Endometriosis was surgically induced in 40 rats by transplanting of
      endometrial tissue. After 3 weeks, repeat laparotomies were performed to check
      the implants and the animals were randomized into four groups: Group I, low-dose
      Dox (5 mg/kg/day); Group II, high-dose Dox (40 mg/kg/day); Group III, leuprolide
      acetate 1 mg/kg single dose, s.c.; and Group VI (controls), no medication. The
      treatment, initiated on the day of surgery and continuing for 3 weeks, was
      administered to the study groups. Three weeks later, the rats were euthanized and
      the implants were evaluated morphologically and histologically for
      immunoreactivity of MMP-2 and -9, and interleukin-6 (IL-6) concentration in the
      peritoneal fluid was assayed. RESULTS: Treatment with leuprolide acetate, or high
      dose or low-dose Dox caused significant decreases in the implant areas compared
      with the controls (P = 0.03, P = 0.006, and P = 0.001, respectively). IL-6 levels
      in peritoneal fluid decreased in Group I (P = 0.02) and Group III (P < 0.05). MMP
      H scores were significantly lower in the group that received low-dose Dox in both
      epithelial and stromal MMP-2 and -9 immunostaining when compared with the control
      group [P = 0.048, P = 0.002, P = 0.007 and P = 0.002, respectively, MMP-2
      (epithelia), MMP-2 (stroma), MMP-9 (epithelia) and MMP-9 (stroma)]. CONCLUSIONS:
      Low-dose Dox caused regression of endometriosis in this experimental rat model.

PMID- 19401322
TI  - Mesenchymal stem cells facilitate the derivation of human embryonic stem cells
      from cryopreserved poor-quality embryos.
AB  - BACKGROUND: Human embryonic stem cells (hESCs) have opened up a new area of
      research in biomedicine. The efficiency of hESC derivation from frozen poor
      quality embryos is low and normally achieved by plating embryos on mouse or human
      foreskin feeders (HFFs). We attempted to optimize embryo survival and hESC
      derivation. METHODS: Three conditions were tested on frozen poor-quality embryos:
      (i) embryo treatment with the Rho-associated kinase (ROCK) inhibitor, Y-27632;
      (ii) use of human mesenchymal stem cells (hMSCs) as feeders; and (iii) laser
      drilling (LD) for inner cell mass (ICM) isolation. Two hundred and nineteen
      thawed embryos were randomly treated with (n = 110) or without (n = 109) 10
      microM Y-27632. Surviving embryos that developed to blastocyst stage (n = 50)
      were randomly co-cultured on HFFs (n = 21) or hMSCs (n = 29). ICM isolation was
      either by whole-blastocyst culture (WBC) or WBC plus LD. RESULTS: Embryo survival
      was 52% higher with Y-27632. hMSCs appeared to facilitate ICM outgrowth and hESC
      derivation: three hESC lines were derived on hMSCs (10.3% efficiency) whereas no
      hESC line was derived on HFFs. ROCK inhibition and ICM isolation method did not
      affect hESC efficiency. The lines derived on hMSCs (AND-1, -2, -3) were
      characterized and showed typical hESC morphology, euploidy, surface marker and
      transcription factor expression and multilineage developmental potential. The
      hESC lines have been stable for over 38 passages on hMSCs. CONCLUSION: Our data
      suggest that Y-27632 increases post-thaw embryo survival and that hMSCs may
      facilitate the efficiency of hESC derivation from frozen poor-quality embryos.

PMID- 19401323
TI  - Clomiphene citrate resistance in relation to follicle-stimulating hormone
      receptor Ser680Ser-polymorphism in polycystic ovary syndrome.
AB  - BACKGROUND: Clomiphene citrate (CC) response in anovulatory women is difficult to
      predict and patient-tailored treatment would benefit patient care and time
      management. The objective of this study was to evaluate the role of the follicle
      stimulating hormone receptor (FSHR) Ser680Ser-polymorphism as a predictor for CC
      response. METHODS: In this retrospective study, 193 patients, diagnosed with
      polycystic ovary syndrome (PCOS) according to Rotterdam criteria and treated with
      ovulation induction, were included over a 5-year period in a university hospital
      in the Netherlands. Data on demographics, BMI, menstrual cycle, laboratory
      screening (including FSHR genotyping), transvaginal ultrasonography of ovaries
      and ovulation parameters were collected. Main outcome measures were response to
      CC and FSHR genotype. RESULTS: The frequency distribution of the 680-polymorphism
      was 26% (Asn/Asn), 50% (Asn/Ser) and 24% (Ser/Ser). No significant differences in
      basal characteristics were found. Significantly more patients with Ser/Ser
      polymorphism were resistant to CC (28%) compared with Asn/Ser (14%) and Asn/Asn
      group (15%), with an odds ratio for ovulation of 0.44 (95% CI, 0.21-0.97).
      Patients with higher FSH levels, higher age and lower BMI were significantly more
      likely to ovulate in univariate analysis. In a multivariate logistic regression
      model, corrected for age, BMI, mean ovarian, volume, hyperandrogenism, and
      amenorrhoea, only FSHR and basal FSH levels were predictive for ovulation.
      CONCLUSIONS: Chance of resistance to CC is almost double in women with PCOS
      harbouring the Ser/Ser genotype.

PMID- 19401324
TI  - Mifepristone acts as progesterone antagonist of non-genomic responses but
      inhibits phytohemagglutinin-induced proliferation in human T cells.
AB  - BACKGROUND: Progesterone is an endogenous immunomodulator that suppresses T cell
      activation during pregnancy. The stimulation of membrane progesterone receptors
      (mPRs) would seem to be the cause of rapid non-genomic responses in human
      peripheral T cells, such as an elevation of intracellular calcium ([Ca(2+)](i))
      and decreased intracellular pH (pH(i)). Mifepristone (RU486) produces mixed
      agonist/antagonist effects on immune cells compared with progesterone. We
      explored whether RU486 is an antagonist to mPRs and can block rapid non-genomic
      responses and the induction by phytohemagglutinin (PHA) of cell proliferation.
      METHODS: Human male peripheral T cell responses in terms of pH(i) and [Ca(2+)](i)
      changes were measured using the fluorescent dyes, 2',7'-bis-(2-carboxyethyl)-5
      (and-6)-carboxyfluorescein (BCECF) and fura-2, respectively. Expression of mPR
      mRNA was determined by RT-PCR analysis. Cell proliferation and cell toxicity were
      determined by [(3)H]-thymidine incorporation and MTT assay, respectively.
      RESULTS: The mRNAs of mPRalpha, mPRbeta and mPRgamma were expressed in T cells.
      RU486 blocked progesterone-mediated rapid responses including, the [Ca(2+)](i)
      increase and pH(i) decrease, in a dose related manner. RU486 did not block, but
      enhanced, the inhibitory effect of progesterone on PHA induced cell
      proliferation. RU486 alone inhibited proliferation induced by PHA and at >25
      microM seems to be cytotoxic against resting T cells (P < 0.01). CONCLUSIONS:
      RU486 is antagonistic to the rapid mPR-mediated non-genomic responses, but is
      synergistic with progesterone with respect to the inhibition of PHA-induced cell
      proliferation. Our findings shine new light on RU486's clinical application and
      how this relates to the non-genomic rapid physiological responses caused by
      progesterone.

PMID- 19401325
TI  - UK deaths from breast cancer fall to lowest figure for 40 years.

PMID- 19401326
TI  - Merck disguised "marketing publication" as medical journal to help promote Vioxx,
      court hears.

PMID- 19401328
TI  - Investigating hirsutism.

PMID- 19401329
TI  - Specific genomic sequences of E. coli promote replicational initiation by
      directly reactivating ADP-DnaA.
AB  - In Escherichia coli, ATP-DnaA, unlike ADP-DnaA, can initiate chromosomal
      replication at oriC. The level of cellular ATP-DnaA fluctuates, peaking at around
      the time of replication initiation. However, it remains unknown how the ATP-DnaA
      level increases coordinately with the replication cycle. In this study, we show
      that two chromosomal intergenic regions, herein termed DnaA-reactivating sequence
      1 (DARS1) and DnaA-reactivating sequence 2 (DARS2), directly promote regeneration
      of ATP-DnaA from ADP-DnaA by nucleotide exchange, resulting in the promotion of
      replication initiation in vitro and in vivo. Coordination of initiation with the
      cell cycle requires DARS activity and its regulation. Oversupply of DARSs results
      in increase in the ATP-DnaA level and enhancement of replication initiation,
      which can inhibit cell growth in an oriC-dependent manner. Deletion of DARSs
      results in decrease in the ATP-DnaA level and inhibition of replication
      initiation, which can cause synthetic lethality with a temperature-sensitive
      mutant dnaA and suppression of overinitiation by the lack of seqA or datA,
      negative regulators for initiation. DARSs bear a cluster of DnaA-binding sites.
      DnaA molecules form specific homomultimers on DARS1, which causes specific
      interactions among the protomers, reducing their affinity for ADP. Our findings
      reveal a novel regulatory pathway that promotes the initiation of chromosomal
      replication via DnaA reactivation.

PMID- 19401330
TI  - An integrin-alpha4-14-3-3zeta-paxillin ternary complex mediates localised Cdc42
      activity and accelerates cell migration.
AB  - Alpha4 integrins are used by leukocytes and neural crest derivatives for adhesion
      and migration during embryogenesis, immune responses and tumour invasion. The pro
      migratory activity of alpha4 integrin is mediated in part through the direct
      binding of the cytoplasmic domain to paxillin. Here, using intermolecular FRET
      and biochemical analyses, we report a novel interaction of the alpha4 integrin
      cytoplasmic domain with 14-3-3zeta. This interaction depends on serine
      phosphorylation of alpha4 integrin at a site (S978) distinct from that which
      regulates paxillin binding (S988). Using a combination of metabolic labelling and
      targeted mass spectrometry by multiple reaction monitoring we demonstrate the low
      stoichiometry phosphorylation of S978. The interaction between alpha4 integrin
      and 14-3-3zeta is enhanced by the direct association between 14-3-3zeta and
      paxillin, resulting in the formation of a ternary complex that stabilises the
      recruitment of each component. Although pair-wise interaction between alpha4
      integrin and paxillin is sufficient for normal Rac1 regulation, the integrity of
      the ternary complex is essential for focused Cdc42 activity at the lamellipodial
      leading edge and directed cell movement. Taken together, these data identify a
      key signalling nexus mediating alpha4 integrin-dependent migration.

PMID- 19401331
TI  - A splice variant of cyclin D2 regulates cardiomyocyte cell cycle through a novel
      protein aggregation pathway.
AB  - The mammalian heart lacks intrinsic ability to replace diseased myocardium with
      newly divided myocytes. There is scant information on mechanisms regulating cell
      cycle exit in cardiomyocytes. We cloned a splice variant of cyclin D2 (D2SV) from
      the mouse heart and found a novel role for this protein in cardiomyocyte cell
      cycle exit. We report that D2SV is highly expressed in embryonic myocardium
      compared with the adult heart. Localization studies indicate that D2SV is
      retained in the endoplasmic reticulum (ER), Golgi and lysosomal compartments and
      subjected to ER-stress-associated protein aggregation. D2SV aggregation relies on
      the motor activities of dynein and is blocked by ER stress modulators. The
      ability of D2SV to sequester other cell cycle proteins provides a mechanistic
      explanation for its effects on cardiomyocyte cell cycle. We show that D2SV
      induced cell cycle exit can be rescued by overexpression of D-type and B-type
      cyclins. We suggest that protein aggregation may be a major block for
      cardiomyocyte cell cycle reactivation.

PMID- 19401332
TI  - The collagen receptor DDR1 regulates cell spreading and motility by associating
      with myosin IIA.
AB  - The spreading and migration of cells on adhesive substrates is regulated by the
      counterbalance of contractile and protrusive forces. Non-muscle myosin IIA, an
      ubiquitously expressed contractile protein and enzyme, is implicated in the
      regulation of cell spreading and directional migration in response to various
      stimuli. Here we show that discoidin domain receptor 1 (DDR1), a tyrosine kinase
      receptor activated by type I collagen, associates with the non-muscle myosin IIA
      heavy chain (NMHC-IIA) upon ligand stimulation. An association was also indicated
      by coimmunoprecipitation of NMHC-IIA with full-length DDR1, but not with the
      truncated DDR1d-isoform lacking the kinase domain. DDR1 was important for
      assembly of NMHC-IIA into filaments on cells plated on collagen. DDR1 expression
      inhibited cell spreading over collagen but promoted cell migration. By contrast,
      blockade of non-muscle myosin II activity by blebbistatin enhanced cell spreading
      but inhibited migration over collagen. We propose that myosin and DDR1 impact
      cell spreading and migration by regulating adhesive contacts with collagen.

PMID- 19401334
TI  - Ancient Leishmania coronin (CRN12) is involved in microtubule remodeling during
      cytokinesis.
AB  - In general, coronins play an important role in actin-based processes, and are
      expressed in a variety of eukaryotic cells, including Leishmania. Here, we show
      that Leishmania coronin preferentially distributes to the distal tip during
      cytokinesis, and interacts with microtubules through a microtubule-based motor,
      kinesin K39. We further show that reduction in coronin levels by 40-50% in
      heterozygous coronin mutants results in generation of bipolar cells (25-30%),
      specifically in the log phase, owing to unregulated growth of the corset
      microtubules. Further analysis of bipolar cells revealed that the main cause of
      generation of bipolar cell morphology is the intrusion of the persistently
      growing corset microtubules into the other daughter cell corset from the opposite
      direction. This defect in cytokinesis, however, disappears upon episomal gene
      complementation. Additionally, our attempts to prepare homozygous mutants were
      unsuccessful, as only the aneuploid cells survive the selection process. These
      results indicate that coronin regulates microtubule remodeling during Leishmania
      cytokinesis and is essentially required for survival of these parasites in
      culture.

PMID- 19401333
TI  - The stratified syncytium of the vertebrate lens.
AB  - The fusion of cells to generate syncytial tissues is a crucial event in the
      development of many organisms. In the lens of the vertebrate eye, proteins and
      other macromolecules diffuse from cell to cell via the large molecule diffusion
      pathway (LMDP). We used the tamoxifen-induced expression of GFP to investigate
      the nature and role of the LMDP in living, intact lenses. Our data indicate that
      the LMPD preferentially connects cells lying within a stratum of the lens cortex
      and that formation of the LMPD depends on the expression of Lim2, a claudin-like
      molecule. The conduits for intercellular protein exchange are most likely regions
      of partial cellular fusion, which are commonly observed in wild-type lenses but
      rare or absent in Lim2-deficient lenses. The observation that lens tissue
      constitutes a stratified syncytium has implications for the transparency,
      refractive function and pathophysiology of the tissue.

PMID- 19401335
TI  - Interaction between PAR-3 and the aPKC-PAR-6 complex is indispensable for apical
      domain development of epithelial cells.
AB  - The evolutionarily conserved polarity proteins PAR-3, atypical protein kinase C
      (aPKC) and PAR-6 critically regulate the apical membrane development required for
      epithelial organ development. However, the molecular mechanisms underlying their
      roles remain to be clarified. We demonstrate that PAR-3 knockdown in MDCK cells
      retards apical protein delivery to the plasma membrane, and eventually leads to
      mislocalized apical domain formation at intercellular regions in both two
      dimensional and three-dimensional culture systems. The defects in PAR-3 knockdown
      cells are efficiently rescued by wild-type PAR-3, but not by a point mutant
      (S827/829A) that lacks the ability to interact with aPKC, indicating that
      formation of the PAR-3-aPKC-PAR-6 complex is essential for apical membrane
      development. This is in sharp contrast with tight junction maturation, which does
      not necessarily depend on the aPKC-PAR-3 interaction, and indicates that the two
      fundamental processes essential for epithelial polarity are differentially
      regulated by these polarity proteins. Importantly, highly depolarized cells
      accumulate aPKC and PAR-6, but not PAR-3, on apical protein-containing vacuoles,
      which become targeted to PAR-3-positive primordial cell-cell contact sites during
      the initial stage of the repolarization process. Therefore, formation of the PAR
      3-aPKC-PAR-6 complex might be required for targeting of not only the aPKC-PAR-6
      complex but also of apical protein carrier vesicles to primordial junction
      structures.

PMID- 19401336
TI  - Mechanosensing in actin stress fibers revealed by a close correlation between
      force and protein localization.
AB  - The mechanics of the actin cytoskeleton have a central role in the regulation of
      cells and tissues, but the details of how molecular sensors recognize
      deformations and forces are elusive. By performing cytoskeleton laser nanosurgery
      in cultured epithelial cells and fibroblasts, we show that the retraction of
      stress fibers (SFs) is restricted to the proximity of the cut and that new
      adhesions form at the retracting end. This suggests that SFs are attached to the
      substrate. A new computational model for SFs confirms this hypothesis and
      predicts the distribution and propagation of contractile forces along the SF. We
      then analyzed the dynamics of zyxin, a focal adhesion protein present in SFs.
      Fluorescent redistribution after laser nanosurgery and drug treatment shows a
      high correlation between the experimentally measured localization of zyxin and
      the computed localization of forces along SFs. Correlative electron microscopy
      reveals that zyxin is recruited very fast to intermediate substrate anchor points
      that are highly tensed upon SF release. A similar acute localization response is
      found if SFs are mechanically perturbed with the cantilever of an atomic force
      microscope. If actin bundles are cut by nanosurgery in living Drosophila egg
      chambers, we also find that zyxin redistribution dynamics correlate to force
      propagation and that zyxin relocates at tensed SF anchor points, demonstrating
      that these processes also occur in living organisms. In summary, our quantitative
      analysis shows that force and protein localization are closely correlated in
      stress fibers, suggesting a very direct force-sensing mechanism along actin
      bundles.

PMID- 19401337
TI  - A novel mode of cell detachment from fibrillar fibronectin matrix under shear.
AB  - Cells within tissues are surrounded by fibrillar extracellular matrix (ECM) that
      supports cell adhesion via integrin receptors. The strength of cell interactions
      with fibrillar matrix and the effects of force on these interactions have not
      been quantified. To this end, we used a spinning disc device to apply radially
      increasing shear to human HT1080 fibrosarcoma cells attached to a cell-derived
      fibrillar fibronectin (FN) matrix. The shear required to detach 50% of HT1080
      cells was eight times greater on a FN-coated, rigid glass substrate than on
      fibrillar FN matrix. Covalent crosslinking of the FN matrix increased its
      stiffness tenfold and produced a modest increase in shear detachment force for
      these cells. On FN-coated surfaces, cells detach by releasing interactions
      between alpha5beta1 integrin and FN. By contrast, cell detachment from fibrillar
      matrix occurred through a novel mechanism of fibril breakage, which left holes in
      the matrix visible by fluorescence microscopy. These results show that cells
      require less force to detach from fibrillar matrix than from FN adsorbed on glass
      and that detachment occurs through breaking fibrils instead of by release of
      integrin-matrix bonds. Thus, ECM fibril breakage is another molecular feature to
      consider when understanding cell and tissue homeostasis.

PMID- 19401338
TI  - Role of syntaxin 18 in the organization of endoplasmic reticulum subdomains.
AB  - The presence of subdomains in the endoplasmic reticulum (ER) enables this
      organelle to perform a variety of functions, yet the mechanisms underlying their
      organization are poorly understood. In the present study, we show that syntaxin
      18, a SNAP (soluble NSF attachment protein) receptor localized in the ER, is
      important for the organization of two ER subdomains, smooth/rough ER membranes
      and ER exit sites. Knockdown of syntaxin 18 caused a global change in ER membrane
      architecture, leading to the segregation of the smooth and rough ER. Furthermore,
      the organization of ER exit sites was markedly changed concomitantly with
      dispersion of the ER-Golgi intermediate compartment and the Golgi complex. These
      morphological changes in the ER were substantially recovered by treatment of
      syntaxin-18-depleted cells with brefeldin A, a reagent that stimulates retrograde
      membrane flow to the ER. These results suggest that syntaxin 18 has an important
      role in ER subdomain organization by mediating the fusion of retrograde membrane
      carriers with the ER membrane.

PMID- 19401339
TI  - Prevalence of flexible bronchoscopic removal of foreign bodies in the advanced
      elderly.
AB  - OBJECTIVES: to define the likelihood and establish the overall safety and
      effectiveness of flexible bronchoscopy in the removal of foreign bodies in the
      advanced elderly compared to those younger. DESIGN: a retrospective case-control
      analysis. SETTING: tertiary care academic hospital. POPULATION: 7,089 adults (age
      >18 years), including 949 (15%) advanced elderly (age >75 years), who underwent
      flexible bronchoscopy between January 1995 and June 2007. MEASUREMENTS: in those
      patients with foreign body aspiration (FBA) (n = 20), a comparison of multiple
      clinical characteristics based on defined age groups (group 1, age <75 years and
      group 2, age >75 years) was performed. RESULTS: FBA requiring bronchoscopic
      removal was greater than three and a half times more likely in patients aged >75
      years compared to those younger (OR 3.78, CI 1.4-10: P <0.05). Flexible
      bronchoscopy was 87.5% effective in the removal of foreign bodies in the advanced
      elderly and associated with no increase in adverse events. CONCLUSION:
      bronchoscopic removal of foreign bodies is more likely in the advanced elderly
      when compared to those younger. This implies that this population may be most at
      risk. Flexible bronchoscopy is a safe and effective initial diagnostic and
      therapeutic approach in this age group.

PMID- 19401340
TI  - Should we be considering gold-tipped ablation electrodes?

PMID- 19401342
TI  - Indications for the use of diagnostic implantable and external ECG loop
      recorders.

PMID- 19401343
TI  - Tissue-specific regulation of porcine prolactin receptor expression by estrogen,
      progesterone, and prolactin.
AB  - Prolactin (PRL) acts through its receptor (PRLR) via both endocrine and local
      paracrine/autocrine pathways to regulate biological processes including
      reproduction and lactation. We analyzed the tissue- and stage of gestation
      specific regulation of PRL and PRLR expression in various tissues of pigs.
      Abundance of pPRLR-long form (LF) mRNA increased in the mammary gland and
      endometrium during gestation while in other tissues it remained constant. There
      was a parallel increase in the abundance of the pPRLR-LF protein in the mammary
      gland and endometrium during gestation. We determined the hormonal regulation of
      pPRLR-LF mRNA expression in various tissues from ovariectomized,
      hypoprolactinemic gilts given combinations of the replacement hormones estrogen
      (E(2)), progestin (P), and/or haloperidol-induced PRL. Abundance of pPRLR-LF mRNA
      in kidney and liver was unaffected by hormone treatments. Expression of uterine
      pPRLR-LF mRNA was induced by E(2) whereas the effect of E(2) was abolished by co
      administering P. The expression of pPRLR-LF mRNA in the mammary gland stroma was
      induced by PRL, whereas E(2) induced its expression in the epithelium. In
      contrast to these changes in pPRLR expression, pPRL expression was relatively
      constant and low during gestation in all tissues except the pituitary. Taken
      together, these data reveal that specific combinations of E(2), P, and PRL
      differentially regulate pPRLR-LF expression in the endometrium and mammary
      glands, and that the action of PRL on its target tissues is dependent upon pPRLR
      LF abundance more so than the local PRL expression.

PMID- 19401341
TI  - Dual-chamber implantable cardioverter defibrillators reduce clinical adverse
      events related to atrial fibrillation when compared with single-chamber
      defibrillators: a subanalysis of the DATAS trial.
AB  - AIMS: The aim of the present analysis of the DATAS study was to compare the
      impact of dual- vs. single-chamber defibrillators on atrial fibrillation (AF)
      occurrence and AF-related clinical events in patients with Class I indication for
      implantable cardioverter defibrillators (ICDs) and no indication for dual-chamber
      pacing. METHODS AND RESULTS: Three hundred and thirty-four patients were
      randomized, through a centralized assignment, to single-chamber ICDs, dual
      chamber ICDs programmed as single-chamber ICDs, and dual ICDs with full
      diagnostics and AF prevention and therapy capabilities. The latter two groups in
      the first 8 months of the study, when the study design was that of a randomized
      parallel trial, were compared in the present analysis. The primary endpoint was
      composed by the following AF-related clinical events: permanent AF, AF-related
      hospitalizations, cardiac-embolic events, and inappropriate ICD shocks due to AF
      misclassification. Two hundred and twenty-three patients were available for this
      analysis, of whom 111 in the single-chamber-simulated group and 112 in the dual
      chamber true group. Atrial fibrillation-related composite endpoint raw incidence
      was 9 of 111 (8.1%) in the single-chamber group vs. 1 of 112 (0.9%) in the dual
      chamber group (P = 0.0098 by Fisher's exact test). Single-chamber ICDs were
      associated with a significantly higher risk to develop the AF-related composite
      endpoint by Cox regression analysis (hazard ratio 8.25, 95% CI 1.03-65.96, P =
      0.047) and by the Kaplan-Meier survival analysis (log-rank test, P = 0.047).
      CONCLUSION: Dual-chamber ICDs compared with single-chamber ICDs reduced the
      incidence of an endpoint composed by permanent AF, AF-related hospitalizations,
      and ICD shocks deemed inappropriate due to AF misclassification.

PMID- 19401344
TI  - A universal formula based on cystatin C to perform individual dosing of
      carboplatin in normal weight, underweight, and obese patients.
AB  - PURPOSE: It has recently been shown that it is possible to improve the prediction
      of carboplatin clearance by adding plasma cystatin C level (cysC), an endogenous
      marker of glomerular filtration rate, to the other patient characteristics
      routinely used for carboplatin individual dosing, namely serum creatinine (Scr),
      actual body weight (ABW), age, and sex. This multicenter pharmacokinetic study
      was done to evaluate prospectively the benefit of using cysC for carboplatin
      individual dosing. EXPERIMENTAL DESIGN: The 357 patients included in the study
      were receiving carboplatin as part of established protocols. A population
      pharmacokinetic analysis was done using NONMEM program. Seven covariates studied
      were as follows: Scr, cysC, age, sex, ABW, ideal body weight, and lean body mass.
      RESULTS: The best covariate equation was as follows: carboplatin clearance
      (mL/min) = 117.8. (Scr/75)(-0.450). (cysC/1,00)(-0.385). (ABW/65)(+0.504).
      (age/56)(-0.366). 0.847(sex), with Scr in micromol/L, cysC in mg/L, ABW in
      kilograms, age in years, and sex = 0 for male. Using an alternative weight
      descriptor (ideal body weight or lean body mass) did not improve the prediction.
      This final covariate model was validated by bootstrap analysis. The bias (mean
      percentage error) and imprecision (mean absolute percentage error) were +1% and
      15%, respectively, on the total population, and were of a similar magnitude in
      each of the three subgroups of patients defined according to their body mass
      index. CONCLUSION: For the first time, a unique formula is proposed for
      carboplatin individual dosing to patients, which is shown to be equally valid for
      underweight, normal weight, and obese patients.

PMID- 19401346
TI  - In vitro and in vivo characterization of MDX-1401 for therapy of malignant
      lymphoma.
AB  - PURPOSE: This study was undertaken to evaluate the effects of MDX-1401, a
      nonfucosylated fully human monoclonal antibody that binds to human CD30, and to
      determine whether it exhibits greater in vitro and in vivo activity than its
      parental antibody. EXPERIMENTAL DESIGN: Assays measuring antibody binding to CD30
      expressing cells and FcgammaRIIIa (CD16) transfectants as well as antibody
      dependent cellular cytotoxicity (ADCC) were conducted. Antitumor activity was
      determined using a Karpas-299 systemic model. RESULTS: The binding of MDX-1401 to
      CD30 antigen was identical to fucose-containing parental anti-CD30 antibody (MDX
      060). In contrast, MDX-1401 showed increased binding affinity to FcgammaRIIIa
      transfected cells resulting in increased effector function. MDX-1401 greatly
      improved ADCC activity as evidenced by a decrease in half-maximal effective
      concentration (EC(50)) and an increase in maximum cell lysis when compared with
      MDX-060. Increased ADCC activity was observed among a panel of cell lines,
      including one with very low CD30 antigen expression in which parental antibody
      failed to induce any detectable ADCC. MDX-1401 activity with all FcgammaRIIIa
      polymorphic variants, including less active Phe/Phe158 and Phe/Val158 effector
      cells, was shown. Furthermore, MDX-1401 was efficacious in inhibiting tumor
      growth in CD30(+) lymphoma xenografts. CONCLUSIONS: The low doses of antibody
      required for ADCC activity irrespective of donor genotype, the ability to mediate
      ADCC in target cells expressing low levels of CD30, and increased in vivo
      efficacy support the development of MDX-1401 for treatment of malignant lymphoma.

PMID- 19401345
TI  - Abnormalities in glucose uptake and metabolism in imatinib-resistant human BCR
      ABL-positive cells.
AB  - The development of imatinib resistance has become a significant therapeutic
      problem in which the etiology seems to be multifactorial and poorly understood.
      As of today, clinical criteria to predict the development of imatinib resistance
      in chronic myelogenous leukemia (CML), other than rebound of the
      myeloproliferation, are under development. However, there is evidence that the
      control of glucose-substrate flux is an important mechanism of the
      antiproliferative action of imatinib because imatinib-resistant gastrointestinal
      stromal KIT-positive tumors reveal highly elevated glucose uptake in radiologic
      images. We used nuclear magnetic resonance spectroscopy and gas chromatography
      mass spectrometry to assess (13)C glucose uptake and metabolism (glycolysis, TCA
      cycle, and nucleic acid ribose synthesis) during imatinib treatment in CML cell
      lines with different sensitivities to imatinib. Our results show that sensitive
      K562-s and LAMA84-s BCR-ABL-positive cells have decreased glucose uptake,
      decreased lactate production, and an improved oxidative TCA cycle following
      imatinib treatment. The resistant K562-r and LAMA84-r cells maintained a highly
      glycolytic metabolic phenotype with elevated glucose uptake and lactate
      production. In addition, oxidative synthesis of RNA ribose from (13)C-glucose via
      glucose-6-phosphate dehydrogenase was decreased, and RNA synthesis via the
      nonoxidative transketolase pathway was increased in imatinib-resistant cells. CML
      cells which exhibited a (oxidative/nonoxidative) flux ratio for nucleic acid
      ribose synthesis of >1 were sensitive to imatinib. The resistant K562-r and
      LAMA84-r exhibited a (oxidative/nonoxidative) flux ratio of <0.7. The changes in
      glucose uptake and metabolism were accompanied by intracellular translocation of
      GLUT-1 from the plasma membrane into the intracellular fraction in sensitive
      cells treated with imatinib, whereas GLUT-1 remained located at the plasma
      membrane in LAMA84-r and K562-r cells. The total protein load of GLUT-1 was
      unchanged among treated sensitive and resistant cell lines. In summary, elevated
      glucose uptake and nonoxidative glycolytic metabolic phenotype can be used as
      sensitive markers for early detection of imatinib resistance in BCR-ABL-positive
      cells.

PMID- 19401347
TI  - gammaH2AX expression in tumors exposed to cisplatin and fractionated irradiation.
AB  - PURPOSE: Is retention of gammaH2AX foci useful as a biomarker for predicting the
      response of xenograft tumors to cisplatin with X-ray? Is a similar approach
      feasible using biopsies from patients with cervical cancer? EXPERIMENTAL DESIGN:
      Mice bearing SiHa, WiDr, or HCT116 xenograft tumors were exposed to cisplatin
      and/or three daily doses of 2 Gy. Tumors were excised 24 h after treatment and
      single cells were analyzed for clonogenic fraction and retention of gammaH2AX
      foci. Tumor biopsies were examined using 47 paraffin-embedded sections from
      untreated tumors and 24 sections from 8 patients undergoing radiochemotherapy for
      advanced cancer of the cervix. RESULTS: Residual gammaH2AX measured 24 h after
      cisplatin injection accurately predicted surviving fraction in SiHa and WiDr
      xenografts. When a clinically equivalent protocol using cisplatin and
      fractionated irradiation was employed, the fraction of xenograft cells lacking
      gammaH2AX ranked survival accurately but underestimated tumor cell kill. Residual
      gammaH2AX foci were detected in clinical samples; on average, only 25% of tumor
      nuclei exhibited one or more gammaH2AX foci before treatment and 74% after the
      start of treatment. CONCLUSION: gammaH2AX can provide useful information on the
      response of human tumors to the combination of cisplatin and radiation, but
      prediction becomes less accurate as more time elapses between treatment and tumor
      biopsy. Use of residual gammaH2AX as a biomarker for response is feasible when
      cell survival exceeds approximately 20%, but heterogeneity in endogenous and
      treatment-induced gammaH2AX must be considered.

PMID- 19401348
TI  - Loss of VHL and hypoxia provokes PAX2 up-regulation in clear cell renal cell
      carcinoma.
AB  - PURPOSE: The paired box gene 2, PAX2, encodes for a transcription factor that is
      up-regulated during nephrogenesis and becomes silenced in mature epithelium of
      the glomeruli, the proximal, and distal tubules. Reactivation of PAX2 has been
      frequently observed in clear cell renal cell carcinoma (ccRCC), a tumor type
      characterized by loss of von Hippel-Lindau (VHL) tumor suppressor function. The
      regulation of PAX2 expression in ccRCC is unknown. EXPERIMENTAL DESIGN: We
      applied reporter gene assays to investigate PAX2 promoter regulation.
      Furthermore, PAX2 expression was determined in ccRCC cell lines under normoxic
      and hypoxic condition in a VHL wild-type and mutated background. PAX2 expression
      was also assessed in 831 human ccRCC and correlated with hypoxia-inducible factor
      alpha (HIFalpha) and clinical parameters. RESULTS: Here, we show that both loss
      of VHL protein (pVHL) function and hypoxia leads to strong PAX2 reexpression.
      Using luciferase reporter gene assays, no induction was obtained in spite of six
      hypoxia response element motifs identified in the promoter of PAX2. Comprehensive
      immunohistochemical analyses showed significant correlations between PAX2,
      HIF1alpha, and HIF2alpha-target CCND1 expression patterns in ccRCC patients.
      Notably, PAX2 expression was highly associated with early-stage, well
      differentiated ccRCC and, consequently, better clinical outcome (P < 0.0001
      each). Additional analyses indicated that PAX2 repressor WT1 and cancer-linked
      hypomethylation are not important for transcriptional regulation of PAX2 in
      ccRCC. CONCLUSION: We conclude that in ccRCC, PAX2 reactivation is driven by HIF
      dependent mechanisms following pVHL loss.

PMID- 19401349
TI  - Ratio of 17HSD1 to 17HSD2 protein expression predicts the outcome of tamoxifen
      treatment in postmenopausal breast cancer patients.
AB  - PURPOSE: Estrogens have great significance in the development of breast cancer.
      After menopause, most estrogen biosynthesis is done in peripheral tissue, and the
      main enzymes involved in balancing the amount of estrone against estradiol are
      17beta-hydroxysteroid dehydrogenases (17HSD). The aim of this study was to
      investigate the prognostic and tamoxifen predictive values of 17HSD1 and 17HSD2
      expression. EXPERIMENTAL DESIGN: Tumors from low-risk breast cancer patients
      randomized to adjuvant tamoxifen therapy or no adjuvant treatment were analyzed
      with immunohistochemistry to investigate protein expression of 17HSD1 and 17HSD2
      in 912 cases. All patients had lymph node-negative breast cancer and were
      postmenopausal at the time of diagnosis. RESULTS: Low 17HSD1 expression was
      associated with significant benefit from tamoxifen treatment among patients with
      estrogen receptor (ER)-positive tumors (P < 0.001). For patients with a 17HSD1
      score not exceeding that of 17HSD2, tamoxifen increased the rate of distant
      recurrence-free survival (hazard ratio, 0.37; 95% confidence interval, 0.23-0.60)
      and breast cancer-specific survival (hazard ratio, 0.30; 95% confidence interval,
      0.16-0.54), whereas no apparent effect was observed when the 17HSD1 score was
      higher than that of 17HSD2. The interaction was significant for both distant
      recurrence-free survival (P = 0.036) and breast cancer-specific survival (P =
      0.014). In the cohort of systemically untreated patients, no prognostic
      importance was observed. CONCLUSIONS: This is the first report that clearly
      distinguishes between the prognostic and predictive importance of 17HSD1 and
      17HSD2 in ER-positive breast cancer treated with or without tamoxifen. Our data
      suggest that the 17HSD1/17HSD2 ratio might be useful as a predictive factor for
      tamoxifen treatment in ER-positive breast cancer patients.

PMID- 19401350
TI  - Treatment of chronic lymphocytic leukemia with a hypomethylating agent induces
      expression of NXF2, an immunogenic cancer testis antigen.
AB  - PURPOSE: Critical to the success of active immunotherapy against cancer is the
      identification of immunologically recognized cancer-specific proteins with low
      tolerogenic potential. Cancer testis antigens (CTA), in particular, fulfill this
      requirement as a result of their aberrant expression restricted to cancer cells
      and lack of expression in normal tissues bypassing tolerogenic mechanisms against
      self. Although CTAs have been extensively studied in solid malignancies, little
      is known regarding their expression in chronic lymphocytic leukemia (CLL).
      EXPERIMENTAL DESIGN: Using a two-pronged approach we evaluated the immunogenicity
      of 29 CTAs in 22 patients with CLL and correlated these results to reverse
      transcriptase PCR data from CLL cell lines and patient cells. RESULTS: We
      identified IgG-specific antibodies for one antigen, NXF2, and confirmed this
      response by ELISA and Western blot. We found that treatment of CLL with 5-aza-2'
      deoxycytidine can induce expression of NXF2 that lasted for several weeks after
      treatment. Treatment also increased levels of MHC and costimulatory molecules
      (CD80, CD86, and CD40) necessary for antigen presentation. In addition, we
      identified other promising antigens that may have potential immunotherapeutic
      application. CONCLUSIONS: Our findings suggest that NXF2 could be further pursued
      as an immunotherapeutic target in CLL, and that treatment with demethylating
      agents could be exploited to specifically modulate CTA expression and effective
      antigen presentation in malignant B cells.

PMID- 19401353
TI  - Relative developmental toxicity of glycol ether alkoxy acid metabolites in the
      embryonic stem cell test as compared with the in vivo potency of their parent
      compounds.
AB  - The embryonic stem cell test (EST) has been proposed as an in vitro assay that
      might reduce animal experimentation in regulatory developmental toxicology. So
      far, evaluation of the EST was not performed using compounds within distinct
      chemical classes. Evaluation within a distinct class of chemically related
      compounds can define the usefulness of the assay for the chemical class tested.
      The aim of the present study was to evaluate the relative sensitivity of the EST
      for a selected series of homologous compounds and to compare the data to the
      relative developmental toxicity of the compounds in vivo. To this end a series of
      proximate developmentally toxic glycol ether alkoxy acid metabolites was tested
      in the EST. All glycol ether alkoxy acid metabolites tested showed a
      concentration-dependent inhibition of cardiomyocyte differentiation at
      noncytotoxic concentrations, with methoxyacetic acid as the most potent compound
      followed by ethoxyacetic acid, butoxyacetic acid, and phenoxyacetic acid,
      respectively. The potency ranking of the compounds in the EST corresponds with
      the available in vivo data. The relative differences between the potencies of the
      compounds appeared more pronounced in the in vivo studies than in the EST. A
      possible explanation for this discrepancy could be the difference in the kinetics
      of the compounds in vivo as compared with their in vitro kinetics. This study
      illustrates that the EST can be used to set priorities for developmental toxicity
      testing within classes of related compounds.

PMID- 19401351
TI  - Zoledronic acid inhibits both the osteolytic and osteoblastic components of
      osteosarcoma lesions in a mouse model.
AB  - PURPOSE: To evaluate the efficacy of zoledronic acid (ZOL) against osteosarcoma
      (OS) growth, progression, and metastatic spread using an animal model of human OS
      that closely resembles the human disease. EXPERIMENTAL DESIGN: Human K-HOS or
      KRIB OS cells, tagged or untagged with a luciferase reporter construct, were
      transplanted directly into the tibial cavity of nude mice. ZOL was given as
      weekly, or a single dose of 100 microg/kg body weight, equivalent to the 4 mg
      i.v. dose used clinically. Tumor growth at the primary site and as pulmonary
      metastases was monitored by bioluminescence imaging and histology, and OS-induced
      bone destruction was measured using high-resolution micro-computed tomography.
      RESULTS: Mice transplanted with OS cells exhibited aberrant bone remodeling in
      the area of cancer cell transplantation, with areas of osteolysis mixed with
      extensive new bone formation extending from the cortex. ZOL administration
      prevented osteolysis and significantly reduced the amount of OS-induced bone
      formation. However, ZOL had no effect on tumor burden at the primary site.
      Importantly, ZOL failed to reduce lung metastasis and in some cases was
      associated with larger and more numerous metastatic lesions. CONCLUSIONS: Our
      data show that clinically relevant doses of ZOL, while protecting the bone from
      OS-induced bone destruction, do not inhibit primary tumor growth. Moreover, lung
      metastases were not reduced and may even have been promoted by this treatment,
      indicating that caution is required when the clinical application of the
      bisphosphonate class of antiresorptives is considered in OS.

PMID- 19401354
TI  - Dental and occlusal features in patients with palatally displaced maxillary
      canines.
AB  - The aim of the present study was to determine the dental and occlusal features
      that could contribute to the aetiology of palatally displaced canines (PDCs). The
      material consisted of pre-treatment dental casts of 50 patients (36 females and
      14 males) with unilateral and bilateral PDCs aged 14-16 years (mean 15.6 +/- 1.6
      years). These were compared with a control group of 50 treated subjects (25 males
      and 25 females) of the same age with normally erupted maxillary canines. The
      following parameters were measured on the dental casts: the mesiodistal (MD) and
      buccolingual (BL) width of each maxillary tooth, the maxillary interpremolar and
      intermolar widths, overjet and overbite, dentoalveolar arch relationship (based
      on incisor classification), and missing or anomalous teeth. The differences
      between the PDC group and controls were determined using a Student's t-test. P
      values less than 0.05 were considered significant. PDCs occurred most frequently
      in subjects with a Class I occlusion. Sixteen per cent of the PDC subjects had
      congenital absence or peg-shaped lateral incisors or congenital absence of the
      second premolar, demonstrating a clear association between palatal impaction of
      the maxillary canine and anomalous or congenital tooth absence. The overjet was
      significantly smaller in the PDC female subjects, especially in those with
      unilateral impaction (P < 0.05). Overbite was significantly greater in PDC male
      subjects compared with the controls, especially in bilateral impaction cases.
      There was no statistically significant difference between the groups with regard
      to the maxillary transverse dimensions, maxillary MD widths, or palatal height
      for either gender.

PMID- 19401355
TI  - A survey on orthodontic retention procedures in The Netherlands.
AB  - The objective of this study was to survey retention procedures used in
      orthodontic practices in The Netherlands. A questionnaire was sent to all 279
      orthodontists working in The Netherlands. The questionnaire consisted of six
      parts, mainly containing multiple-choice questions. Information as to background
      data on the individual orthodontist, retention in general, frequency of different
      types of removable or bonded retainers that were used, retention protocol, and
      the type and size of the wire used for bonded retainers was assessed. All
      statistical analyses were performed using Statistical Package for Social Sciences
      version 12.0.1. Tests for the relationship between two items were based on the
      chi-square test. The overall response rate was 91 per cent. Most orthodontists
      placed a bonded retainer in the upper and lower arch, except when the upper arch
      was expanded during treatment or when extractions were performed in the upper
      arch, in which case they placed a removable retainer. Opinions varied with regard
      to how many hours the removable retainers should be worn and the duration of the
      retention phase. Contraindications for bonded retainers were given by 96 per cent
      of the orthodontists, with poor oral hygiene being the most commonly mentioned.
      As far as bonded retainers were concerned, 84 per cent of the orthodontists
      preferred permanent retention. Fifty-nine per cent of the orthodontists believed
      that a practice guideline for retention after orthodontic treatment needs to be
      developed, which was confirmed by the varied responses in this survey.

PMID- 19401356
TI  - Are nano-composites and nano-ionomers suitable for orthodontic bracket bonding?
AB  - The aim of this study was to test nano-composite (Filtek Supreme Plus Universal)
      and a newly introduced nano-ionomer (Ketac N100 Light Curing Nano-Ionomer)
      restorative to determine their shear bond strength (SBS) and failure site
      locations in comparison with a conventional light-cure orthodontic bonding
      adhesive (Transbond XT). Sixty freshly extracted human maxillary premolar teeth
      were arbitrarily divided into three equal groups. The brackets were bonded to the
      teeth in each group with different composites, according to the manufacturers'
      instructions. The SBS values of the brackets were recorded in Megapascals (MPa)
      using a universal testing machine. Adhesive remnant index scores were determined
      after failure of the brackets. The data were analysed using analysis of variance,
      Tukey honestly significant difference, and chi-square tests. The results
      demonstrated that group 1 (Transbond XT, mean: 12.60 +/- 4.48 MPa) had a higher
      SBS than that of group 2 (nano-composite, mean: 8.33 +/- 5.16 MPa; P < 0.05) and
      group 3 (nano-ionomer, mean: 6.14 +/- 2.12 MPa; P < 0.001). No significant
      differences in debond locations were found among the three groups. Nano
      composites and nano-ionomers may be suitable for bonding since they fulfil the
      previously suggested SBS ranges for clinical acceptability, but they are inferior
      to a conventional orthodontic composite.

PMID- 19401358
TI  - Measuring burden of disease in Estonia to support public health policy.
AB  - BACKGROUND: Many countries have an overview on mortality and morbidity but few
      have performed contextualized national burden of disease studies. The objective
      of the present study is to provide a first set of national and sub-national
      burden of disease estimates for Estonia. Further, we present the causes and age
      gender distribution of the burden. We conclude with the description of result
      uptake and impact of the study in Estonian public health policy arena. METHODS: A
      burden of disease estimation procedure modified for best fit to country situation
      was used. That included disease classification reflecting Estonian disease
      profile, national disease severity assessments, mortality and morbidity
      prevalence data. Calculations were performed on national and sub-national levels.
      RESULTS: Estonian population lost 446 361 (327/1000 persons) disability adjusted
      life-years in 2002. Premature mortality caused majority of the burden and
      cardiovascular diseases, external causes (e.g. suicide and injuries) and cancers
      were main sources of burden. Working age population (16-64 years) shouldered 60%
      of the burden. Sub-national levels of burden range from 114 to 725 disability
      adjusted life-years per 1000 persons and are correlated to regional socioeconomic
      development. CONCLUSION: Cardiovascular disease and injuries, premature
      mortality, working age population, male and people from economically less
      developed regions should be the priority targets for public health interventions.
      Estonian main public health strategies now address burden of disease concerns
      highlighted by our study.

PMID- 19401357
TI  - Urban-rural differences in the effect of a Medicare health promotion and disease
      self-management program on physical function and health care expenditures.
AB  - PURPOSE: To evaluate the impact of a multicomponent health promotion and disease
      self-management intervention on physical function and health care expenditures
      among Medicare beneficiaries. To determine if these outcomes vary by urban or
      rural residence. DESIGN AND METHODS: We analyzed data from a 22-month randomized
      controlled trial of a health promotion/disease self-management program that
      included 766 elderly Medicare beneficiaries from western New York, West Virginia,
      and Ohio. Physical function was measured by changes in self-reported dependencies
      in activities of daily living over the study period. Total health care
      expenditures were measured by aggregating expenditures from major sources (acute,
      postacute, and long-term care). We used ordinary least squares models to examine
      the effects of the intervention on both physical function and cost outcomes
      during the 22-month period. RESULTS: The results indicated that the intervention
      reduced physical functional decline by 54% (p = .03) in the study sample.
      Stratified analyses showed that the intervention effect was much stronger in the
      rural sample. Mean total health care expenditures were 11% ($3,100, p = .30)
      lower in the intervention group. The effects of the intervention on average
      health care expenditures were similar among urban and rural participants.
      IMPLICATIONS: The intervention offered a promising strategy for reducing decline
      in physical function and potentially lowering total health care expenditures for
      high-risk Medicare beneficiaries, especially for those in rural areas. Future
      studies need to investigate whether the findings can be replicated in other types
      of rural areas through a refined intervention and better targeting of the study
      population.

PMID- 19401359
TI  - Contemporary treatment principles for early rheumatoid arthritis: a consensus
      statement.
AB  - OBJECTIVE: RA has a substantial impact on both patients and healthcare systems.
      Our objective is to advance the understanding of modern management principles in
      light of recent evidence concerning the condition's diagnosis and treatment.
      METHODS: A group of practicing UK rheumatologists formulated contemporary
      management principles and clinical practice recommendations concerning both
      diagnosis and treatment. Areas of clinical uncertainty were documented, leading
      to research recommendations. RESULTS: A fundamental concept governing treatment
      of RA is minimization of cumulative inflammation, referred to as the inflammation
      time area under the curve (AUC). To achieve this, four core principles of
      management were identified: (i) detect and refer patients early, even if the
      diagnosis is uncertain: patients should be referred at the first suspicion of
      persistent inflammatory polyarthritis and rheumatology departments should provide
      rapid access to a diagnostic and prognostic service; (ii) treat RA immediately:
      optimizing outcomes with conventional DMARDs and biologics requires that
      effective treatment be started early-ideally within 3 months of symptom onset;
      (iii) tight control of inflammation in RA improves outcome: frequent assessments
      and an objective protocol should be used to make treatment changes that maintain
      low-disease activity/remission at an agreed target; (iv) consider the risk
      benefit ratio and tailor treatment to each patient: differing patient, disease
      and drug characteristics require long-term monitoring of risks and benefits with
      adaptations of treatments to suit individual circumstances. CONCLUSION: These
      principles focus on effective control of the inflammatory process in RA, but
      optimal uptake may require changes in service provision to accommodate
      appropriate care pathways.

PMID- 19401360
TI  - Providing information on pregnancy complications during antenatal visits: unmet
      educational needs in sub-Saharan Africa.
AB  - INTRODUCTION: Lack of information on the warning signs of complications during
      pregnancy, parturition and postpartum hampers women's ability to partake fully in
      safe motherhood initiatives. We assessed the extent to which women in 19
      countries of sub-Saharan Africa recall receiving information about pregnancy
      complications during antenatal care for the most recent pregnancy, and examined
      the impact of advice receipt on the likelihood of institutional delivery.
      METHODS: A cross-sectional, cross-country analysis was performed on data from the
      most recent Demographic and Health Surveys (DHS) of 19 countries of sub-Saharan
      Africa. Multilevel logistic regressions were used to predict the probability of
      receiving information and delivering in a health centre, by clinical risk factors
      (age, parity, previous pregnancy termination), social factors (area of residence,
      education), and the frequency of service utilization (number of visits). RESULTS:
      The percentage of women recalling information about potential complications of
      pregnancy during antenatal care varied widely, ranging from 6% in Rwanda to 72%
      in Malawi, and in 15 of the 19 countries, less than 50% of women reported
      receiving information. Institutional delivery ranged from 29% (Ethiopia) to 92%
      (Congo Brazzaville). Teenagers (OR = 0.84), uneducated (OR = 0.65) and rural
      women (OR = 0.70) were less likely to have been advised, compared with women aged
      20-34 years, women with secondary education and urban women, respectively.
      Likelihood of recalling information increased with the number of antenatal
      visits. Advice reception interacts with the number of antenatal visits to
      increase the likelihood of institutional delivery. CONCLUSION: There is a high
      level of unmet need for information on pregnancy complications in sub-Saharan
      Africa, particularly among those who face significant barriers to accessing care
      if complications occur. Educational interventions are critical to safe motherhood
      initiatives; health providers must fully use the educational opportunity in
      antenatal care.

PMID- 19401361
TI  - Putting propylthiouracil in perspective.

PMID- 19401362
TI  - Carrier-mediated thyroid hormone transport into placenta by placental
      transthyretin.
AB  - CONTEXT: The serum protein transthyretin (TTR) plays an important role in the
      transport of thyroid hormone and retinol, which are critical for normal
      development of the human fetus. TTR is not only synthesized and secreted into the
      circulation by the liver and other tissues but is also synthesized by placental
      trophoblasts, which separate the maternal and fetal circulations. Whether it is
      secreted or taken up by these cells and whether it carries thyroid hormone is
      unknown. OBJECTIVE AND METHODS: Our objective was to study placental handling of
      TTR and determine whether TTR participates in placental thyroid hormone
      transport. We investigated the capacity of human placenta and choriocarcinoma
      cell lines to secrete and internalize TTR and its ligands by Western blotting,
      immunofluorescence, and uptake of radiolabeled TTR. RESULTS: Human placental
      explants and TTR expressing JEG-3 cells secrete TTR. JEG-3 cells grown in
      bicameral chambers secrete TTR, predominantly from the apical surface. Human
      placental explants and JEG-3 cells internalize Alexa Fluor488-labeled TTR and
      (125)I-TTR. Furthermore, binding to thyroid hormones (T(4), T(3)) increases
      (125)I-TTR uptake by enhancing tetramer formation. Cross-linking experiments
      confirm internalization of the TTR-(125)I-T(4) complex. CONCLUSIONS: Our results
      suggest that human placenta and choriocarcinoma cells secrete transthyretin,
      which binds extracellular T(4), and that T(4) binding results in increased
      internalization of TTR-T(4) complex. TTR production by trophoblasts may represent
      a mechanism to allow transfer of maternal thyroid hormone to the fetal
      circulation that could have important implications for fetal development.

PMID- 19401363
TI  - Association between serum insulin-like growth factor (IGF) I and IGF binding
      protein-3 and lung function.
AB  - BACKGROUND: There is strong evidence that IGF-I and IGF binding protein 3 (IGFBP
      3), as central mediators of endocrine and finally metabolic or anabolic effects
      of GH, were associated with increased lung size in acromegaly or a decrease of
      respiratory muscle pressures in patients with GH deficiency. The aim of the
      present study was to further clarify the impact of IGF-I and IGFBP-3 levels on
      lung volumes and respiratory pressures in a general adult population. MATERIAL
      AND METHODS: From the Study of Health in Pomerania, 1326 subjects aged 25 to 85
      yr participated in standardized pulmonary function testing. IGF-I and IGFBP-3
      levels were measured with the Immulite 2500 system. Multivariable linear
      regression analyses adjusted for age, sex, body mass index, physical activity,
      and smoking were performed. RESULTS: In men, positive linear associations between
      IGF-I and IGF-I/IGFBP-3 ratio with forced expiratory volume in 1 sec (FEV1) as
      well as with forced vital capacity (FVC) were detected across all ages, whereas
      in women this positive association was only detectable above 50 yr. Furthermore,
      the analyses indicated positive linear relations of IGF-I/IGFBP-3 ratio with FEV1
      and FVC, respectively. No significant relations between IGF-I or IGFBP-3 and
      maximal inspiratory pressure was detectable in both sexes. CONCLUSION: In
      conclusion, higher IGF-I levels were associated with higher lung volumes in men,
      whereas in women this association was only detectable in subjects older than 50
      yr. Higher IGF-I values were not associated with increased respiratory muscle
      strength measured as maximal inspiratory pressure.

PMID- 19401364
TI  - Identification and characterization of two novel truncated but functional
      isoforms of the somatostatin receptor subtype 5 differentially present in
      pituitary tumors.
AB  - CONTEXT: Somatostatin and its related peptide cortistatin exert multiple actions
      on normal and tumoral tissue targets through a family of receptors termed
      somatostatin receptor (sst)1-5. Despite the considerable advances in the
      knowledge on these receptors and their (patho)physiological roles, there is still
      evidence that additional receptors for these peptides should exist to fully
      explain their actions. OBJECTIVE: The growing number of spliced variants found in
      similar receptor families, often present in tumors, and results from our group
      obtained on sst5 from other species (pig) led us to explore the existence of new
      human sst5 isoforms. DESIGN AND RESULTS: A rapid amplification of cDNA ends PCR
      approach on samples from a human pituitary tumor and a cell line enabled
      identification of two novel alternatively spliced sst5 receptor variants. The
      sequences obtained encode putative proteins that correspond to truncated isoforms
      of five and four transmembrane domains (TMDs), accordingly named sst5TMD5 and
      sst5TMD4, respectively. Both novel receptors show a differential expression
      pattern in normal tissues and are also present in pituitary tumors of diverse
      etiology including nonfunctioning adenomas, corticotropinomas, somatotropinomas,
      and a prolactinoma. In contrast to the predominant plasma membrane localization
      of full-length sst5, both sst5TMD5 and sst5TMD4 show a preferentially
      intracellular localization. Despite their truncated nature, both receptors are
      functional, as shown by their ability to mediate selective, ligand-induced rises
      in free cytosolic calcium concentration. Specifically, whereas sst5TMD5 is
      selectivity activated by somatostatin compared with cortistatin, cells
      transfected with sst5TMD4 almost exclusively respond to cortistatin and not to
      somatostatin. CONCLUSIONS: Our results demonstrate the existence of two
      previously unidentified sst5 spliced variants with distinct distribution in
      normal tissues and pituitary tumors, unique ligand-selective signaling
      properties, and subcellular distribution, which could contribute to somatostatin
      and cortistatin signaling in normal and tumoral cells.

PMID- 19401365
TI  - Clinical review: An automated method for determination of bone age.
AB  - CONTEXT: Bone age rating is associated with a considerable rater variability,
      which limits its usefulness in modern pediatric endocrinology. An automated
      computerized method would theoretically solve this problem but has been
      surprisingly difficult to establish. EVIDENCE ACQUISITION: We review the
      development of automated bone age assessment and describe how the conceptual
      understanding of bone age rating shifted from a rule-based theory to a more
      intuitive and experience-based approach. The role of the CASAS system from 1992
      is described. The BoneXpert system from 2008 employs deformable models of each
      bone to locate the bones and extracts the component of the bone appearance
      related to maturity in a holistic, statistical manner. Two clinical studies have
      been published on its accuracy, defined as the root mean square deviation from
      manual rating. Other studies addressed the precision of the method, defined as
      its ability to give the same result on a repeated x-ray, expressed as the sd on a
      single measurement. EVIDENCE SYNTHESIS: The accuracy of the automated bone age
      determination was 0.71-0.72 yr, and the precision was 0.17-0.18 yr. More than
      98.6% of the images could be analyzed. The system was validated on children with
      various diagnoses of short stature in the bone age range 2.5-17 yr for boys and 2
      15 yr for girls. CONCLUSION: The reviewed validation studies suggest that this
      automated bone age determination system has adequate accuracy, precision, and
      efficiency to be clinically useful.

PMID- 19401366
TI  - Growth response, near-adult height, and patterns of growth and puberty in
      patients with noonan syndrome treated with growth hormone.
AB  - CONTEXT: Noonan syndrome (NS) is a heterogeneous genetic disorder characterized
      by short stature. SETTING: The National Cooperative Growth Study (NCGS), a
      postmarketing observational study of recombinant human GH (rhGH)-treated
      children, includes a large cohort of children with NS. PATIENTS: We studied NCGS
      enrolled prepubertal and pubertal children with NS. MAIN OUTCOMES: Baseline
      characteristics and growth responses in NS patients with reported near-adult
      height (NAH) (n = 65) were compared to patients with idiopathic GH deficiency (n
      = 3007) and Turner syndrome (TS; n = 1378) with reported NAH to identify factors
      contributing to NAH optimization in NS. RESULTS: NS patients (mean enrollment
      age, 11.6 yr) received rhGH (mean, 0.33 mg/kg . wk) for a mean of 5.6 yr. No
      significant difference was observed in Delta height sd score (SDS) between NS
      (+1.4 +/- 0.7) and TS (+1.2 +/- 0.9). However, Delta height SDS for NS and TS
      differed significantly from idiopathic GH deficiency (+1.7 +/- 1.0) (P < 0.0001).
      Mean gain in NAH above projected was 10.9 +/- 4.9 cm (males) and 9.2 +/- 4.0 cm
      (females). Duration of prepubertal rhGH was an important contributor to
      prepubertal change in height SDS (r(2) = 0.97). Height SDS at pubertal onset
      highly correlated with NAH SDS (rho = 0.783; P < 0.0001). Duration of puberty
      highly correlated with pubertal height gain in centimeters for males (rho =
      0.941) and females (rho = 0.882) (P < 0.01). No new adverse events were observed.
      CONCLUSIONS: rhGH significantly improved height SDS for children with NS at NAH.
      Duration of prepubertal rhGH and height SDS at puberty were important
      contributors to NAH. Because starting age of the patients in this report was 11.6
      yr, these data suggest that greater growth optimization is possible with earlier
      initiation of therapy.

PMID- 19401367
TI  - Hypothyroidism secondary to hypothalamic-pituitary dysfunction may be part of the
      phenotype in klinefelter syndrome: a case-control study.
AB  - CONTEXT: Klinefelter syndrome (KS) may involve a number of abnormalities besides
      the characteristic testicular insufficiency. Some studies have suggested that
      thyroid abnormalities may be common, but this has not been clarified. DESIGN: A
      case-control study of men with KS (n = 75) compared with age-matched men from the
      general population (n = 75) was organized, and thyroid function, thyroid volume
      by ultrasonography, and thyroid antibodies were examined. RESULTS: Men with KS
      were on average taller and heavier and tended to have a higher body mass index
      than the men in the control group. Serum free T(4) (fT4) was lower in men with KS
      than controls [mean (sd): 16.3 (2.35) vs. 17.6 (1.75) pmol/liter; P < 0.001],
      with clustering in or just below the lower part of the reference range for the
      assay. The ratio fT4 to free T(3) was low in KS (P < 0.001), whereas no
      differences between groups were observed in TSH, free T(3), TSH to fT4 ratio,
      thyroid volume, or the prevalence of thyroid antibodies. No difference in any of
      the variables were observed between testosterone-treated and untreated KS men.
      Adjustment for differences in height, weight, and concomitant disease in
      multivariate models did not alter the results. CONCLUSIONS: Men with KS had a
      general shift toward lower values in distribution of serum fT4 with no
      compensatory increase in serum TSH. The most likely mechanism is a decrease or
      change in set point of thyrotroph control of thyroid function.

PMID- 19401369
TI  - Role of unilateral adrenalectomy in bilateral primary aldosteronism: a 22-year
      single center experience.
AB  - OBJECTIVE: The aim of the study was to examine blood pressure and biochemical
      responses to unilateral adrenalectomy in patients with bilateral primary
      aldosteronism (PA) and identify predictive parameters. CONTEXT: PA considered due
      to bilateral autonomous production of aldosterone is usually treated medically.
      Unilateral adrenalectomy has been considered ineffective. Because quality outcome
      data are lacking and medical treatment may cause adverse effects or fail to
      control hypertension, defining the role for unilateral adrenalectomy in bilateral
      PA is an important clinical issue. DESIGN AND SETTING: Between 1984 and 2004, 51
      of 684 patients diagnosed with bilateral PA underwent unilateral adrenalectomy.
      This report is based on the records of the 40 considered suitable for inclusion,
      who were followed for at least 12 (median, 56.4) months. RESULTS: Hypertension
      was cured in 15% of patients and improved in 20%, usually within 1 yr of
      unilateral adrenalectomy. The proportion with controlled hypertension was
      significantly (P < 0.001) higher after adrenalectomy (65%) than before (25%).
      Mean systolic (P < 0.001) and diastolic (P < 0.001) blood pressure, left
      ventricular mass index (P < 0.05), plasma upright aldosterone (P < 0.05), and
      aldosterone/renin ratio (P < 0.001) fell. Serum creatinine independently
      predicted hypertension cure. CONCLUSION: Although this retrospective analysis of
      patients from a single center does not permit prediction of response rates among
      patients diagnosed elsewhere, it suggests that unilateral adrenalectomy can be
      beneficial in some patients with apparent bilateral PA and should not be
      dismissed as a treatment option.

PMID- 19401368
TI  - Effects of teriparatide retreatment in osteoporotic men and women.
AB  - CONTEXT: The stimulatory effect of teriparatide on bone mineral density (BMD) and
      bone turnover is initially exuberant, but then diminishes. OBJECTIVE: Our
      objective was to determine whether retreating with teriparatide after a drug-free
      period can restore the initial exuberant response to teriparatide. DESIGN AND
      SETTING: This was a planned extension of a randomized controlled trial conducted
      in a single university hospital. PATIENTS AND INTERVENTION: Subjects previously
      participated in a 30-month randomized trial comparing the effects of alendronate
      (group 1), teriparatide (group 2), or both (group 3) on BMD and bone turnover in
      men and women with low BMD (phase 1). Subjects who completed phase 1 on their
      assigned therapy entered phase 2 (months 30-42), during which teriparatide was
      stopped in groups 2 and 3. Teriparatide was administered to all subjects during
      months 42 to 54 (phase 3). MAIN OUTCOME MEASURES: We compared changes in BMD and
      markers of bone turnover (serum osteocalcin, N-terminal propeptide of type 1
      collagen, and N-telopeptide) between phase 1 and 3 in subjects receiving
      teriparatide alone. RESULTS: Posterior-anterior and lateral spine BMD increased
      12.5 +/- 1.5 and 16.9 +/- 1.7%, respectively, during the first 12 months of
      teriparatide administration and 5.2 +/- 0.8 and 6.2 +/- 1.8%, respectively,
      during teriparatide retreatment (P < 0.001 and P = 0.001). Increases in
      osteocalcin (P < 0.001), N-terminal propeptide of type 1 collagen (P < 0.001),
      and N-telopeptide (P < 0.001) were greater during the first period of
      teriparatide administration. CONCLUSION: The response to teriparatide is
      attenuated when readministered after a 12-month hiatus.

PMID- 19401370
TI  - Primary testicular dysfunction is a major contributor to abnormal pubertal
      development in males with Prader-Willi syndrome.
AB  - BACKGROUND: Recent studies challenge the assumption that hypogonadism in Prader
      Willi syndrome (PWS) is due only to hypothalamic dysfunction. OBJECTIVES: The
      aims of the study were to characterize sexual development and reproductive
      hormones in PWS males and investigate the etiology of hypogonadism. METHODS:
      Physical examination and blood sampling were performed on 37 PWS males, ages 4
      months to 32 yr. RESULTS: All had a history of undescended testes; age at
      orchiopexy ranged from 2 months to 6 yr. Pubertal signs were variable, but none
      achieved full genital development. Anti-Mullerian hormone (AMH) levels in PWS
      boys were near the lower limits of normal, decreasing from 44.4 +/- 17.8 ng/ml
      (mean +/- sd) in young children to 5.9 +/- 4.7 ng/ml in adolescents, similar to
      normal males. In contrast, inhibin B was consistently low (27.1 +/- 36.1 pg/ml)
      or undetectable in all age groups. In adult males, FSH levels were high (20.3 +/-
      18.3 IU/liter), LH levels were normal (4.2 +/- 4.3 IU/liter), and testosterone
      levels were low (1.87 +/- 1.17 ng/ml). Only two adults had severe
      hypogonadotropic hypogonadism with undetectable levels of LH and FSH and high AMH
      levels (34.9 and 36.7 ng/ml), unlike the other nine adults with AMH levels 2.6 +/
      2.1 ng/ml. Androstenedione (1.06 +/- 0.30 ng/ml) and DHEAS (281.1 +/- 143.6
      microg/dl) in adult PWS were normal. CONCLUSIONS: Pubertal development in PWS is
      characterized by normal adrenarche, variable hypothalamic dysfunction, and
      hypogonadism due to a unique testicular defect. Primary testicular dysfunction is
      a major component of hypogonadism in PWS.

PMID- 19401371
TI  - The role of genetic variation in the lamin a/c gene in the etiology of polycystic
      ovary syndrome.
AB  - OBJECTIVE: We performed this study to test the hypothesis that variation in the
      lamin a/c gene (LMNA) contributes to milder phenotypes of insulin resistance,
      hyperandrogenism, and/or metabolic syndrome associated with polycystic ovary
      syndrome (PCOS). RESEARCH DESIGN AND METHODS: We resequenced the coding region,
      flanking intronic, and proximal promoter regions of the lamin a/c gene in 43
      women with PCOS with evidence of upper-body obesity (waist circumference >88 cm)
      and identified 56 variants, two of which were nonsynonymous substitutions (lmna11
      exon1 E98D; lmna24 exon 7 R455C). We genotyped 53 single-nucleotide polymorphisms
      (44 identified through resequencing and nine included to maximize informativeness
      of the entire gene) in 624 index (PCOS) cases and 544 controls of European
      ancestry. We tested for association between these variants and PCOS. In a subset
      of individuals, we also tested for association with metabolic syndrome and
      quantitative traits (body mass index, waist circumference, total testosterone,
      dehydroepiandrosterone sulfate, fasting glucose and insulin, low-density
      lipoprotein, and total triglycerides). RESULTS: After correction for multiple
      testing, none of the variants showed significant evidence for association with
      PCOS, the metabolic syndrome, or any of the quantitative traits tested.
      CONCLUSIONS: Whereas these studies cannot exclude the role of genetic variation
      in the lamin a/c gene in isolated cases of PCOS, we can conclude that common
      variation in the lamin a/c gene does not contribute to the etiology of PCOS in
      women of European ancestry.

PMID- 19401372
TI  - The effect of age on insulin sensitivity and insulin secretion in first-degree
      relatives of type 1 diabetic patients: a population analysis.
AB  - CONTEXT: Understanding the role of insulin resistance in type 1 diabetes may lead
      to new prevention strategies. Estimates of insulin resistance in first-degree
      relatives of those with type 1 diabetes may be obtained using the minimal model
      of glucose kinetics incorporating a population approach. OBJECTIVE: The objective
      of the study was to explore parameters contributing to glucose homeostasis in a
      cross-sectional study of first-degree relatives across a wide age range. DESIGN:
      Insulin sensitivity (SI) was assessed using the minimal model of glucose kinetics
      after an oral glucose tolerance test combined with nonlinear mixed-effects
      modeling. Beta-cell function was measured from the insulinogenic index at 30 min
      (IGI(30)). Disposition index (DI) was estimated as the product of SI and IGI(30).
      SETTING: The study was conducted at an academic center. SUBJECTS: Subjects
      included 1241 first-degree relatives (aged 2-75 yr). RESULTS: SI was found to be
      negatively correlated with age, whereas IGI(30) increased until young adulthood.
      The increase IGI(30) was apparently insufficient to compensate for the insulin
      resistance because DI decreased linearly at the rate of 0.035 (10(-2) min(-1)
      mmol(-1) liter per year) after young adulthood. Both IGI(30) and DI were
      significantly lower in those with vs. without autoantibodies, whereas there was
      no difference between these groups with respect to SI. CONCLUSIONS: Beta-cell
      function, adjusted for age-related insulin resistance, decreases throughout life
      in first-degree relatives. This deterioration may be exacerbated in the presence
      of autoantibodies. Oral glucose tolerance test data combined with a nonlinear
      mixed-effect modeling population approach may be a useful technique to evaluate
      SI and secretion in a population.

PMID- 19401373
TI  - Low serum testosterone and estradiol predict mortality in elderly men.
AB  - CONTEXT: Age-related reduction of serum testosterone may contribute to the signs
      and symptoms of aging, but previous studies report conflicting evidence about
      testosterone levels and male mortality. No large prospective cohort study has
      determined a possible association between serum estradiol and mortality in men.
      OBJECTIVE: The main objective was to examine the association between serum
      testosterone and estradiol and all-cause mortality in elderly men. DESIGN,
      SETTING, AND PARTICIPANTS: We used specific gas chromatography-mass spectrometry
      to analyze serum sex steroids at baseline in older men who participated in the
      prospective population-based MrOS Sweden cohort (n = 3014; mean age, 75 yr;
      range, 69-80 yr). MAIN OUTCOME MEASURE: All-cause mortality by serum testosterone
      and estradiol levels. RESULTS: During a mean follow-up period of 4.5 yr, 383
      deaths occurred. In multivariate hazards regression models, low levels (within
      quartile 1 vs. quartiles 2-4) of both testosterone [hazard ratio (HR), 1.65; 95%
      confidence interval (CI), 1.29-2.12] and estradiol (HR, 1.54; 95% CI, 1.22-1.95)
      associated with mortality. A model including both hormones showed that both low
      testosterone (HR, 1.46; 95% CI, 1.11-1.92) and estradiol (HR, 1.33; 95% CI, 1.02
      1.73) predicted mortality. Risk of death nearly doubled (HR, 1.96; 95% CI, 1.46
      2.62) in subjects with low levels of both testosterone and estradiol compared
      with subjects within quartiles 2-4 of both hormones. CONCLUSIONS: Elderly men
      with low serum testosterone and estradiol have increased risk of mortality, and
      subjects with low values of both testosterone and estradiol have the highest risk
      of mortality.

PMID- 19401374
TI  - Fat mass is negatively associated with cortical bone size in young healthy male
      siblings.
AB  - CONTEXT: Body weight has been associated with bone mass and bone size through
      shared genetic determination and environmental influences. Whereas lean mass
      exerts a positive influence on bone size, the relationship between fat and bone
      remains unclear. OBJECTIVE: The objective of the present study was to investigate
      the individual influence of fat mass and lean mass on volumetric bone density and
      size in young healthy male siblings at age of peak bone mass. DESIGN: This was a
      cross-sectional, population-based sibling pair study. PARTICIPANTS: A total of
      677 men (25-45 yr) were included in this study with 296 independent pairs of
      brothers. MAIN OUTCOME MEASURES: Areal and volumetric bone parameters were
      determined using dual-energy X-ray absorptiometry (DXA) and peripheral
      quantitative computed tomography (pQCT). Body composition was determined by DXA.
      Sex steroids, leptin, and adiponectin were determined by immunoassay. RESULTS:
      Total and regional fat mass were found to be inversely associated with areal bone
      mass and bone size, independent from lean mass (radius periosteal circumference
      beta: -0.29 +/- 0.04; P < 0.001). Lean mass was positively associated with bone
      size but inversely with cortical density at both tibia and radius (P < 0.01). The
      negative association between total fat mass and bone size was independent from
      sex steroid concentrations. Leptin but not adiponectin was inversely associated
      with bone size, but this was no longer significant after adjustment for body fat.
      CONCLUSIONS: Increased fat mass is associated with smaller bone size, challenging
      the view of a high bone mass index as a protective factor for osteoporosis,
      whereas lean mass was a consistent positive determinant of bone size.

PMID- 19401375
TI  - Appetite responds to changes in meal content, whereas ghrelin, leptin, and
      insulin track changes in energy availability.
AB  - CONTEXT: It is uncertain how between-meal variations in energy availability and
      physiological changes in ghrelin, leptin, and insulin affect appetite. OBJECTIVE:
      The aim of the study was to examine the influence on human appetite of the meal
      size and its nutrient content or changes in energy availability and
      concentrations of ghrelin, leptin, and insulin. DESIGN: We conducted a crossover
      study manipulating meal size and energy availability through exercise energy
      expenditure and iv nutrient replacement (TPN). SETTING: The study was performed
      at a Clinical Research Center. PARTICIPANTS: Ten healthy postmenopausal women
      (age, 59.7 +/- 1.5 yr; mean body mass index, 26 kg/m(2)) were studied.
      INTERVENTIONS: We conducted trials based on different morning meal size (418 vs.
      2090 KJ), presence or absence of exercise energy expenditure (2273 to 2361 KJ),
      energy replacement by TPN (1521 to 1538 KJ), and a midday ad libitum meal. MAIN
      OUTCOME MEASURES: Changes in hunger, fullness, midday ad libitum food
      consumption, and concentrations of ghrelin, leptin, insulin, and metabolic fuels
      were measured. We also performed midday meal tests for the presence of caloric
      compensation. RESULTS: Appetite was influenced by the size and energy content of
      the meals, but not by variation in energy availability which also did not trigger
      consummatory compensation. Exercise reduced hunger and increased fullness.
      Ghrelin, leptin, and insulin responded to changes in energy availability but not
      to meal size. Appetite was unaffected by physiological changes in ghrelin,
      leptin, or insulin. CONCLUSIONS: During rest, appetite is influenced by the size
      and energy content of meals, but it bears no homeostatic relationship to between
      meal changes in energy availability due to small meals, exercise, or TPN, or
      concentrations of ghrelin, leptin, and insulin.

PMID- 19401377
TI  - Short-term administration of a combination of recombinant growth hormone and
      insulin-like growth factor-I induces anabolism in maintenance hemodialysis.
AB  - CONTEXT: Resistance to GH and IGF-I is a significant complication of severe
      chronic kidney disease, which contributes to muscle wasting. Pharmacological
      doses of recombinant human (rh) GH or rhIGF-I have been proposed to treat this
      catabolic condition. OBJECTIVE: This study was undertaken to examine the
      potential additive anabolic effects of rhGH + rhIGF-I compared with rhIGF-I.
      DESIGN: We studied eight well-nourished hemodialysis patients in a random
      crossover design and compared the metabolic effects of a 3-d administration of
      moderate dose of rhIGF-I (40 microg/kg per 12h) with an association of rhIGF-I +
      rhGH (50 microg/kg/d). Leucine kinetics, plasma amino acids (AAs), serum insulin,
      and IGF binding proteins (IGFBP)-1 and -3 were measured. RESULTS: The net protein
      balance was not affected by rhIGF-I alone, whereas serum insulin and IGFBP-3
      decreased (P < 0.05) and IGFBP-1 increased (P < 0.01). With the combination rhGH
      + rhIGF-I, an increase of IGFBP-3 (P < 0.01) and insulin (P < 0.01) as well as a
      decrease of IGFBP-1 (P < 0.01) occurred. Plasma essential AAs (P = 0.01) as well
      as the essential to nonessential AA ratio (P < 0.001) decreased. Whole-body
      protein net balance increased significantly (P < 0.05) with a 22% decrease in
      leucine oxidation and a 15% increase in nonoxidative leucine disposal.
      CONCLUSIONS: In dialysis patients, rhIGF-I administration at a moderate dose has
      no protein metabolic effect, but the association with a moderate dose of rhGH is
      followed by a significant anabolic response.

PMID- 19401376
TI  - Osteoclastogenesis in children with 21-hydroxylase deficiency on long-term
      glucocorticoid therapy: the role of receptor activator of nuclear factor-kappaB
      ligand/osteoprotegerin imbalance.
AB  - CONTEXT: Children with 21-hydroxylase deficiency (21-OHD) need chronic
      glucocorticoid (cGC) therapy to replace congenital deficit of cortisol synthesis.
      cGC therapy is the most frequent and severe form of drug-induced osteoporosis,
      and different mechanisms have been proposed to explain its pathogenesis.
      OBJECTIVE: We investigated the osteoclastogenic potential of peripheral blood
      mononuclear cells (PBMCs) from 18 children with 21-OHD on cGC therapy and 25
      controls who never received GCs. We also evaluated the presence of circulating
      osteoclast precursors (OCPs) and the role of T cells in osteoclast formation.
      RESULTS: Spontaneous osteoclastogenesis, without adding macrophage-colony
      stimulating factor and receptor activator of nuclear factor-kappaB ligand
      (RANKL), and significantly higher osteoclasts resorption activity occurred in 21
      OHD patients. Conversely, macrophage-colony stimulating factor and RANKL were
      essential to trigger and sustain osteoclastogenesis in controls. Furthermore, in
      21-OHD patients, we identified a significant percentage of CD11b-CD51/CD61 and
      CD51/61-RANK-positive cells, which are OCPs strongly committed. Additionally, we
      demonstrated a T cell-dependent osteoclastogenesis from 21-OHD patients' PBMCs. T
      cells from patients expressed high levels of RANKL and low levels of
      osteoprotegerin (OPG) with respect to controls. Moreover, 21-OHD patients had
      higher soluble RANKL and lower OPG serum levels compared with controls; thus,
      soluble RANKL to OPG ratio was significantly higher in patients than controls.
      CONCLUSIONS: The present study showed for the first time a high osteoclastogenic
      potential of PBMCs from 21-OHD patients on cGC therapy. This spontaneous
      osteoclastogenesis seems to be supported by both the presence of circulating OCPs
      and factors released by T cells.

PMID- 19401378
TI  - Morphometric vertebral fractures in postmenopausal women with primary
      hyperparathyroidism.
AB  - CONTEXT: An increased risk of fracture in patients with primary
      hyperparathyroidism (PHPT) compared to the general population has been reported,
      but available data are controversial. OBJECTIVE: The aim of the study was to
      evaluate the rate of vertebral fractures (VFs) by dual-energy x-ray
      absorptiometry in postmenopausal women with sporadic PHPT and compare the results
      with a control group. DESIGN AND SETTING: A case-control study was performed at a
      referral center. PARTICIPANTS: A total of 150 consecutive patients and 300
      healthy women matched for age and menopausal age participated in the study.
      RESULTS: VFs were detected in 37 of 150 (24.6%) patients and 12 of 300 (4.0%)
      controls (P < 0.0001). The majority of VFs were mild. Stepwise multiple logistic
      regression analysis showed that in PHPT patients lumbar spine bone mineral
      density was the only variable independently associated with the prevalence of VFs
      (P = 0.003). The rate of fracture was higher in symptomatic (34.1%) than
      asymptomatic (21.1%) patients, but this difference was not statistically
      significant (P = 0.15). Among asymptomatic patients, fracture rate was
      significantly higher in those who met the criteria for parathyroidectomy (28.1%)
      than in those who did not (11.1%) (P = 0.03). Compared to controls, the fracture
      rate was significantly higher in patients with symptomatic and asymptomatic PHPT
      who met the criteria for surgery (P < 0.0001), but not in those who did not meet
      the criteria (P = 0.06). CONCLUSIONS: VF rate is increased in postmenopausal
      women with PHPT compared to controls, independently of whether they are
      classified as symptomatic or asymptomatic. The question of whether the finding of
      mild morphometric VFs in the latter represents an indication for parathyroid
      surgery remains to be established.

PMID- 19401379
TI  - Bone mineral density in estrogen-deficient young women.
AB  - CONTEXT: Osteoporosis primarily affects postmenopausal women. However, young
      women with estrogen deficiency also are at increased risk for low bone density.
      OBJECTIVE: The aim of the study was to assess bone density and associated risk
      factors for reduced bone density in young, estrogen-deficient women using primary
      ovarian insufficiency (POI) as the disease model. DESIGN AND SETTING: We
      conducted a cross-sectional study at a tertiary care research center.
      PARTICIPANTS: We studied women with POI (n = 442), concurrent controls (n = 70),
      and matched controls from NHANES III (n = 353). PRIMARY OUTCOME MEASURE: We
      measured bone mineral density (BMD) using dual-energy x-ray absorptiometry.
      RESULTS: Patients on average had 2-3% lower BMD at L1-L4, femoral neck, and total
      hip (P < 0.01 at all sites). The modifiable risk factors for BMD below the
      expected range for age (Z-score <-2) were: more than 1-yr delay in diagnosis of
      estrogen deficiency (P = 0.018), low (<32 ng/ml) vitamin D levels (P = 0.002),
      estrogen replacement nonadherence (P = 0.002), low calcium intake (P = 0.005),
      and lack of exercise (P = 0.005). As compared to Caucasians, African-American and
      Asian women with POI were 3.18 and 4.34 times more likely, respectively, to have
      Z-scores below -2 (P = < 0.0001 for both). Race was an overall risk factor, but
      on regression modeling, not an independent predictor of low bone density.
      CONCLUSIONS: Women with POI have lower bone density compared to regularly
      menstruating women. Compared to Caucasians, minority women with estrogen
      deficiency are more likely to have BMD below the expected range for age. This
      racial disparity appears to be related to a combined effect of several modifiable
      risk factors. Delay in diagnosis of POI also contributes to reduced bone density
      by delaying proper therapy.

PMID- 19401382
TI  - TLR2 ligands augment cPLA2alpha activity and lead to enhanced leukotriene release
      in human monocytes.
AB  - Toll-like receptors (TLRs) play an important role in innate immunity. They detect
      pathogen-associated receptor patterns (PAMPs) and initiate subsequent immune
      responses. Present studies investigate the influence of TLR2 ligands on
      leukotrienes (LT) formation in human monocytes. LTs are proinflammatory mediators
      derived from arachidonic acid (AA), which is released from membranes by
      phospholipase A(2) (PLA(2)) enzymes. Pretreatment of MM6 cells with the TLR2
      ligands LTA, FSL-1, or Pam(3)CSK(4) resulted in an up to two- to threefold
      enhancement of ionophore-induced LT formation in a dose- and time-dependent
      manner and to an augmentation of ionophore-induced AA release with similar
      kinetics. Also in human peripheral blood mononuclear cells (hPBMC), TLR2
      activators increased LT formation. Studies with PLA(2) inhibitors indicated that
      the increase of AA release is a result of enhanced activity of group IV cPLA(2)
      in MM6 cells. TLR2 ligands elicited the time-dependent activation of p38 MAPK and
      ERK1/2 pathways, which led to phosphorylation of cPLA(2)alpha at Ser(505).
      Simultaneous inhibition of p38 MAPK and ERK1/2 pathways prevented the increase of
      cPLA(2)alpha phosphorylation and the augmentation of AA release. TLR2 ligand
      induced increase of AA release was blocked by a neutralizing anti-hTLR2 antibody,
      indicating that TLR2 mediates augmented cPLA(2) activation and subsequent LT
      biosynthesis.

PMID- 19401380
TI  - Emotional attention in acquired prosopagnosia.
AB  - The present study investigated whether emotionally expressive faces guide
      attention and modulate fMRI activity in fusiform gyrus in acquired prosopagnosia.
      Patient PS, a pure case of acquired prosopagnosia with intact right middle
      fusiform gyrus, performed two behavioral experiments and a functional imaging
      experiment to address these questions. In a visual search task involving face
      stimuli, PS was faster to select the target face when it was expressing fear or
      happiness as compared to when it was emotionally neutral. In a change detection
      task, PS detected significantly more changes when the changed face was fearful as
      compared to when it was neutral. Finally, an fMRI experiment showed enhanced
      activation to emotionally expressive faces and bodies in right fusiform gyrus. In
      addition, PS showed normal body-selective activation in right fusiform gyrus,
      partially overlapping the fusiform face area. Together these behavioral and
      neuroimaging results show that attention was preferentially allocated to
      emotional faces in patient PS, as observed in healthy subjects. We conclude that
      systems involved in the emotional guidance of attention by facial expression can
      function normally in acquired prosopagnosia, and can thus be dissociated from
      systems involved in face identification.

PMID- 19401383
TI  - The membrane expression of Neisseria meningitidis adhesin A (NadA) increases the
      proimmune effects of MenB OMVs on human macrophages, compared with NadA- OMVs,
      without further stimulating their proinflammatory activity on circulating
      monocytes.
AB  - Hypervirulent MenB causing fatal human infections frequently display the
      oligomeric-coiled coil adhesin NadA, a 45-kDa intrinsic outer membrane protein
      implicated in binding to and invasion of respiratory epithelial cells. A
      recombinant soluble mutant lacking the 10-kDa COOH terminal membrane domain
      (NadA(Delta351-405)) also activates human monocytes/macrophages/DCs. As NadA is
      physiologically released during sepsis as part of OMVs, in this study, we tested
      the hypothesis that NadA(+) OMVs have an enhanced or modified
      proinflammatory/proimmune action compared with NadA(-) OMVs. To do this we
      investigated the activity of purified free NadA(Delta351-405) and of OMVs from
      MenB and Escherichia coli strains, expressing or not full-length NadA.
      NadA(Delta351-405) stimulated monocytes and macrophages to secrete cytokines (IL
      1beta, TNF-alpha, IL-6, IL-12p40, IL-12p70, IL-10) and chemokines (IL-8, MIP
      1alpha, MCP-1, RANTES), and full-length NadA improved MenB OMV activity,
      preferentially on macrophages, and only increased cytokine release. NadA(Delta351
      405) induced the lymphocyte costimulant CD80 in monocytes and macrophages, and
      NadA(+) OMVs induced a wider set of molecules supporting antigen presentation
      (CD80, CD86, HLA-DR, and ICAM-1) more efficiently than NadA(-) OMVs only in
      macrophages. Moreover, membrane NadA effects, unlike NadA(Delta351-405) ones,
      were much less IFN-gamma-sensitive. The activity of NadA-positive E. coli OMVs
      was similar to that of control OMVs. NadA in MenB OMVs acted at adhesin
      concentrations approximately 10(6) times lower than those required to stimulate
      cells with free NadA(Delta351-405).

PMID- 19401384
TI  - Two structurally identical mannose-specific jacalin-related lectins display
      different effects on human T lymphocyte activation and cell death.
AB  - Plant lectins displaying similar single sugar-binding specificity and identical
      molecular structure might present various biological effects. To explore this
      possibility, the effects on human lymphocytes of two mannose-specific and
      structurally closely related lectins, Morniga M from Morus nigra and artocarpin
      from Artocarpus integrifolia were investigated. In silico analysis revealed that
      Morniga M presents a more largely open carbohydrate-binding cavity than
      artocarpin, probably allowing interactions with a broader spectrum of
      carbohydrate moieties. In vitro, Morniga M interacted strongly with the
      lymphocyte surface and was uptaken quickly by cells. Morniga M and artocarpin
      triggered the proliferation and activation of human T and NK lymphocytes. A
      minority of B lymphocytes was activated in artocarpin-treated culture, whereas
      Morniga M favored the emergence of CD4+ CD8+ T lymphocytes. Moreover, cell death
      occurred in activated PBMC, activated T lymphocytes, and Jurkat T leukemia cells
      incubated with Morniga M only. The biological effects of both lectins were
      dependent on carbohydrate recognition. The Morniga M-induced cell death resulted,
      at least in part, from caspase-dependent apoptosis and FADD-dependent receptor
      mediated cell death. Finally, Morniga M, but not artocarpin, triggered AICD of T
      lymphocytes. In conclusion, both lectins trigger lymphocyte activation, but only
      Morniga M induces cell death. In spite of similar in vitro mannose-binding
      specificities and virtually identical structure, only Morniga M probably
      interacts with carbohydrate moieties bound to molecules able to induce cell
      death. The present data suggest that subtle alterations in N-glycans can
      distinguish activation and cell death molecules at the lymphocyte surface.

PMID- 19401381
TI  - Web-queryable large-scale data sets for hypothesis generation in plant biology.
AB  - The approaching end of the 21st century's first decade marks an exciting time for
      plant biology. Several National Science Foundation Arabidopsis 2010 Projects will
      conclude, and whether or not the stated goal of the National Science Foundation
      2010 Program-to determine the function of 25,000 Arabidopsis genes by 2010-is
      reached, these projects and others in a similar vein, such as those performed by
      the AtGenExpress Consortium and various plant genome sequencing initiatives, have
      generated important and unprecedented large-scale data sets. While providing
      significant biological insights for the individual laboratories that generated
      them, these data sets, in conjunction with the appropriate tools, are also
      permitting plant biologists worldwide to gain new insights into their own
      biological systems of interest, often at a mouse click through a Web browser.
      This review provides an overview of several such genomic, epigenomic,
      transcriptomic, proteomic, and metabolomic data sets and describes Web-based
      tools for querying them in the context of hypothesis generation for plant
      biology. We provide five biological examples of how such tools and data sets have
      been used to provide biological insight.

PMID- 19401385
TI  - Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-gamma expression in
      activated human T cells.
AB  - The zinc transporter ZIP8 is highly expressed in T cells derived from human
      subjects. T cell ZIP8 expression was markedly up-regulated upon in vitro
      activation. T cells collected from human subjects who had received oral zinc
      supplementation (15 mg/day) had higher expression of the activation marker IFN
      gamma upon in vitro activation, indicating a potentiating effect of zinc on T
      cell activation. Similarly, in vitro zinc treatment of T cells along with
      activation resulted in increased IFN-gamma expression with a maximum effect at
      3.1 microM. Knockdown of ZIP8 in T cells by siRNA decreased ZIP8 levels in
      nonactivated and activated cells and concomitantly reduced secretion of IFN-gamma
      and perforin, both signatures of activation. Overexpression of ZIP8 by transient
      transfection caused T cells to exhibit enhanced activation. Confocal microscopy
      established that ZIP8 is localized to the lysosome where ZIP8 abundance is
      increased upon activation. Loss of lysosomal labile zinc in response to
      activation was measured by flow cytometry using a zinc fluorophore. Zinc between
      0.8 and 3.1 microM reduced CN phosphatase activity. CN was also inhibited by the
      CN inhibitor FK506 and ZIP8 overexpression. The results suggest that zinc at low
      concentrations, through inhibition of CN, sustains phosphorylation of the
      transcription factor CREB, yielding greater IFN-gamma expression in T cells.
      ZIP8, through control of zinc transport from the lysosome, may provide a
      secondary level of IFN-gamma regulation in T cells.

PMID- 19401386
TI  - PPARgamma regulates retinoic acid-mediated DC induction of Tregs.
AB  - CD4+ CD25+ Foxp3+ Tregs are critical regulators of immune responses and
      autoimmune diseases. nTregs are thymically derived; iTregs are converted in the
      periphery from CD4+ CD25- Foxp3- Teffs. Recent studies reported that GALT CD103+
      DCs mediated enhanced iTreg conversion via the secretion of RA. However, the
      factors regulating RA secretion and hence, the induction of iTregs by DCs are not
      yet clear. Activation of the nuclear hormone receptor PPARgamma has been shown to
      induce RA expression in human DCs, and thus, we postulated that PPARgamma
      activation in DCs may be an important regulator of RA secretion and iTreg
      generation. Using in vitro and in vivo approaches, we now demonstrate that
      PPARgamma activation enhances iTreg generation through increased RA synthesis
      from murine splenic DCs. In addition, we demonstrate that inhibition of DC
      PPARgamma decreases iTreg generation, suggesting a role for endogenous PPARgamma
      ligands in this process. Overall, our findings suggest that PPARgamma may be
      important as a factor that stimulates DCs to produce RA and as a potential
      mechanism by which PPARgamma ligands ameliorate autoimmunity.

PMID- 19401388
TI  - Ca2+-dependent mast cell death induced by Ag (I) via cardiolipin oxidation and
      ATP depletion.
AB  - In genetically susceptible humans and/or experimental animals, ions of heavy
      metals, Hg (II), Au (III), and Ag (I) have been shown to strongly induce
      autoimmunity, in which mast cells have been implicated to play a role. Here, we
      demonstrate that Ag (I) application results in mast cell death through a unique
      Ca(2+)- and mitochondria-dependent pathway. As cellular susceptibilities to Ag
      (I) cytotoxicity varied considerably, we analyzed the cell death pathway in the
      low and high responding cells. In the low responding cells, long application
      (e.g., 20 h) of Ag (I) at concentrations (>or=30 microM) induced cell death,
      which was accompanied by mitochondrial membrane depolarization, cyt c release,
      and caspase-3/7 activation but was not prevented by selective inhibitors of
      caspase-3/7 and the mitochondrial permeability transition. The cell death was
      preceded by elevations in the cytoplasmic and mitochondrial Ca(2+) levels, and
      Ca(2+) responses and cell death were prevented by thiol reagents, including DTT,
      N-acetylcysteine, and reduced glutathione monoethyl ester. In the high responding
      cells, Ag (I) evoked considerable cell death by necrosis within 1 h, without
      inducing caspase activation, and this cell death was reduced significantly by
      depleting extracellular but not intracellular Ca(2+). Moreover, Ag (I) strongly
      induced Ca(2+)-dependent CL oxidation and intracellular ATP depletion, both of
      which were blocked by thiol reagents. These results suggest that Ag (I) activates
      thiol-dependent Ca(2+) channels, thereby promoting Ca(2+)-dependent CL oxidation,
      cyt c release, and ATP depletion. This necrotic cell death may play roles in Ag
      induced inflammation and autoimmune disorders.

PMID- 19401387
TI  - Lethal pulmonary infection with Francisella novicida is associated with severe
      sepsis.
AB  - The bacterial or host determinants of lethality associated with respiratory
      Francisella infections are currently unknown. No exo- or endotoxins that
      contribute to the severity of this disease have been identified. However, a
      deregulated host immune response upon infection is characterized by an initial 36
      to 48-h delay followed by a rapid and excessive inflammatory response prior to
      death at 72-120 h. Here, we extend these findings by comparing host immune
      responses between sublethal and lethal respiratory infections of mice with an
      attenuated transposon mutant (Mut) of F. novicida (F.n.) strain U112 (sublethal)
      versus the wild-type (WT) strain (lethal). Infection with WT bacteria, but not
      the Mut, was characterized by sustained bacteremia and systemic dissemination of
      the pathogen with temporal increases in bacterial burdens in liver and spleen.
      Severe pathology with large foci of infiltrates associated with extensive tissue
      damage was evident in WT-infected lungs, and Mut-infected mice displayed much
      reduced pathology with intact lung architecture. Similar to other experimental
      models of severe sepsis, WT- but not the Mut-infected mice exhibited a robust
      increase in numbers of Gr1+ and CD11b+ cells, while displaying a significant
      depletion of alphabeta T cells. Further, a dramatic up-regulation of multiple
      cytokines and chemokines was observed only in lethal WT infection. In addition,
      an earlier and larger increased expression of S100A9, a known mediator of sepsis,
      was observed in WT-infected mice. Taken together, these results show that a
      hyperinflammatory host immune response, culminating in severe sepsis, is
      responsible for the lethal outcome of respiratory tularemia.

PMID- 19401389
TI  - T cell suppression by naturally occurring HLA-G-expressing regulatory CD4+ T
      cells is IL-10-dependent and reversible.
AB  - CD4(+) T cells constitutively expressing the immune-tolerogenic HLA-G have been
      described recently as a new type of nT(reg) (HLA-G(pos) T(reg)) in humans. HLA
      G(pos) T(reg) accumulate at sites of inflammation and are potent suppressors of T
      cell proliferation in vitro, suggesting their role in immune regulation. We here
      characterize the mechanism of how CD4(+) HLA-G(pos) T(reg) influence autologous
      HLA-G(neg) T(resp) function. Using a suppression system free of APC, we
      demonstrate a T-T cell interaction, resulting in suppression of HLA-G(neg)
      T(resp), which is facilitated by TCR engagement on HLA-G(pos) T(reg). Suppression
      is independent of cell-cell contact and is reversible, as the removal of HLA
      G(pos) T(reg) from the established coculture restored the proliferative
      capability of responder cells. Further, HLA-G(pos) T(reg)-mediated suppression
      critically depends on the secretion of IL-10 but not TGF-beta.

PMID- 19401391
TI  - Src family kinases are necessary for cell migration induced by extracellular
      HMGB1.
AB  - HMGB1 is a nuclear protein that signals tissue damage, as it is released by cells
      dying traumatically or secreted by activated innate immunity cells. Extracellular
      HMGB1 elicits the migration to the site of tissue damage of several cell types,
      including inflammatory cells and stem cells. The identity of the signaling
      pathways activated by extracellular HMGB1 is not known completely: We reported
      previously that ERK and NF-kappaB pathways are involved, and we report here that
      Src is also activated. The ablation of Src or inhibition with the kinase
      inhibitor PP2 blocks migration toward HMGB1. Src associates to and mediates the
      phosphorylation of FAK and the formation of focal adhesions.

PMID- 19401392
TI  - IFN-alpha amplifies human naive B cell TLR-9-mediated activation and Ig
      production.
AB  - TLRs are a family of molecules that function as sensors for the detection of
      pathogens. TLR-9, expressed on B cells and pDCs, recognizes CpG motifs of
      unmethylated bacterial DNA and plays a role in the development of autoimmunity.
      The present study was designed to investigate the effects of IFN-alpha in
      combination with CpG ODN on the activation of CD27(-) naive B cells and on Ig
      production. We provide evidence that CpG ODN not only induces a total and T
      dependent, specific IgM response by naive B cells but also their phenotypic
      differentiation in plasma cells, as demonstrated by the up-regulation of CD38
      expression. We found that TLR-9 stimulation with CpG ODN induces IL-1beta, TNF
      alpha, IL-10, and IL-6 production. Interestingly, we also found that CpG ODN
      induces naive B cell maturation into memory cells, as demonstrated by the
      induction of CD27, AID mRNA expression, and IgG production. More importantly, our
      results demonstrate that IFN-alpha amplifies the inductive effect of CpG ODN on
      naive B activation and on Ig production through a mechanism involving TLR-9/MyD88
      dependent signaling. Moreover, we found that IFN-alpha enhances the frequency of
      CpG ODN-induced memory B cells. Our results may contribute to clarify the events
      promoting IFN-alpha-induced amplification of naive B cell activation via TLR-9
      for a better understanding of the pathogenesis of autoimmune disorders and may
      guide treatments targeting this pathway within B cells.

PMID- 19401390
TI  - AGE-modified albumin containing infusion solutions boosts septicaemia and
      inflammation in experimental peritonitis.
AB  - HSA preparations for i.v. use are administered in critically ill patients.
      Although increasing intravascular osmotic pressure seems to be a
      pathophysiologically orientated treatment, clinical trials do not indicate a
      benefit for mortality in HSA-treated patients. Instead, there is evidence for
      inflammatory reactions upon infusion of different HSA batches. A neglected issue
      concerning the safety and quality of these therapeutics is processing-related
      post-transcriptional protein modifications, such as AGEs. We therefore tested the
      hypothesis that commercially available infusion solutions contain AGEs and
      studied whether these protein modifications influence outcome and inflammation in
      a murine model of sepsis induced by CLP. Screening of different HSA and Ig
      preparations in this study revealed an up to approximate tenfold difference in
      the amount of AGE modifications. Application of clinically relevant
      concentrations of CML-modified HSA in CLP led to increased inflammation and
      enhanced mortality in wild-type mice but not in mice lacking the RAGE. Lethality
      was paralleled by increased activation of the proinflammatory transcription
      factor NF-kappaB, NF-kappaB-dependent gene expression, and infiltration of
      inflammatory cells in the peritoneal cavity. This study implies that infusion
      solutions containing a high load of the AGE-modified protein have the potential
      to activate RAGE/NF-kappaB-mediated inflammatory reactions, causing increased
      mortality in experimental peritonitis.

PMID- 19401393
TI  - Hypoxia increases macrophage motility, possibly by decreasing the heparan sulfate
      proteoglycan biosynthesis.
AB  - Macrophages are recruited and retained in hypoxic sites in atherosclerotic
      lesions and tumors. Furthermore, macrophages are suggested to be a major source
      of HSPG synthesis in atherosclerotic lesions. HSPG are, among other things, known
      to regulate cell motility, cell adhesion, and receptor interaction. The aim of
      this study was to investigate the effect of hypoxia on HSPG expression and
      macrophage motility. We also explored the potential regulation of HSPG by the
      transcription factor HIF-1alpha. The nondirected cell motility was increased in
      HMDM after 24 h exposure to hypoxia (0.5% O(2)) compared with normal cell culture
      condition (21% O(2)). Enzymatic degradation of HS GAG further increased the
      motility of the HMDM in hypoxia, indicating a role of reduced cell-associated
      HSPG in the increased HMDM motility. HMDM exposed to 24 h of hypoxia had lower
      mRNA expressions of syndecan-1 and -4 compared with cells exposed to normal cell
      culture conditions. Protein levels of syndecan-1 were also decreased
      significantly in response to hypoxia, and cells subjected to hypoxia had lower
      mRNA expression for key enzymes involved in HS biosynthesis. In addition, hypoxia
      was found to reduce the relative content of HS GAG. Transfecting THP-1 cells with
      siHIF-1alpha indicated that this transcription factor was not involved in the
      hypoxia-induced modifications of HSPG expression. Given the documented multiple
      functions of HSPG in macrophage behavior, the hypoxia-induced modifications of
      HSPG may be of relevance for the development of atherosclerotic lesions and tumor
      progression.

PMID- 19401394
TI  - Galectin-8 provides costimulatory and proliferative signals to T lymphocytes.
AB  - Galectin (Gal) constitute a family of carbohydrate-recognizing molecules
      ubiquitously expressed in mammals. In the immune system, they regulate many
      processes such as inflammation, adhesion, and apoptosis. Here, we report the
      expression in the spleen of the two same Gal-8 splice variants described
      previously in the thymus. Gal-8 was found to induce two separate biological
      activities on T lymphocytes: a robust naive CD4(+) T cell proliferation in the
      absence of antigen and notably, a costimulatory signal that synergized the
      cognate OVA peptide in DO11.10 mice transgenic for TCR(OVA). The antigen
      independent proliferation induced by Gal-8 displayed increased expression of pro-
      and anti-inflammatory cytokines, thus suggesting the polyclonal expansion of Th1
      and Th2 clones. The costimulatory effect on antigen-specific T cell activation
      was evidenced when the Gal and the peptide were assayed at doses suboptimal to
      induce T cell proliferation. By mass spectra analysis, several integrins and
      leukocyte surface markers, including CD45 isoforms, as well as other molecules
      specific to macrophages, neutrophils, and platelets, were identified as putative
      Gal-8 counter-receptors. Gal-8 triggered pZAP70 and pERK1/2. Moreover,
      pretreatment with specific inhibitors of CD45 phosphatase or ERK1/2 prevented its
      antigen-dependent and -independent T cell-proliferative activities. This seems to
      be associated with the agonistic binding to CD45, which lowers the activation
      threshold of the TCR signaling pathway. Taken together, our findings support a
      distinctive role for locally produced Gal-8 as an enhancer of otherwise
      borderline immune responses and also suggest that Gal-8 might fuel the reactivity
      at inflammatory foci.

PMID- 19401396
TI  - CD4 and CD8: an inside-out coreceptor model for innate immune cells.
AB  - CD8 and CD4 are expressed by several cell types that do not express TCR. These
      include DCs, macrophages, monocytes, and NK cells. CD8(+) monocytes and
      macrophages are abundant at the site of pathology in many rat disease models,
      particularly those involving immune complex-mediated pathology. Indeed, in some
      disease models, CD8(+) macrophages correlate with severity of pathology or
      directly cause pathology or tumor cell killing. Evidence suggests CD8 or CD4 can
      enhance FcgammaR-dependent responses of human monocytes. Building on data that
      key components of TCR and FcgammaR signaling can substitute one another
      efficiently, we postulate that CD4 and CD8 operate with FcgammaR and potentially
      other receptors to enhance responses of T cells and various innate immune cells.
      Our model suggests CD8 on myeloid cells may contribute directly to tumor killing
      and tissue pathology by enhancing FcgammaR responses. Moreover, the model
      suggests a role for CD8 in cross-presentation of antibody-associated antigen by
      DCs and a new mechanism to regulate TCR sensitivity.

PMID- 19401395
TI  - A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune
      evasion by negatively regulating IL-10 induction.
AB  - Mtb dysregulates monocyte/macrophage functions to produce a large amount of the
      immunosuppressive cytokine IL-10. An important function of IL-10 in promoting Mtb
      survival is the suppression of antigen presentation of monocytes/macrophages to T
      cells. This dampens the host immune responses and provides an opportunity for
      immune evasion. GSK3 has been shown to control the balance between pro- and anti
      inflammatory cytokine productions. Here, we investigated whether GSK3 regulates
      IL-10 expression and mediates a protective role upon live mycobacterial challenge
      using BCG as a model. Our results showed that BCG increased Akt phosphorylation
      and inhibited GSK3 activity, resulting in increased IL-10 production. We
      confirmed further that suppression of GSK3 activities by a specific chemical
      inhibitor strongly enhanced BCG-induced IL-10 production. We also showed that IL
      10 secreted by BCG-infected human PBMo was a major suppressor of subsequent IFN
      gamma production by PBMC and HLA-DR expression on PBMo in response to BCG.
      Neutralization of PBMo-secreted IL-10 by anti-IL-10 antibodies restored the IFN
      gamma production and HLA-DR surface expression. Taken together, GSK3 negatively
      regulates mycobacteria-induced IL-10 production in human PBMo. The kinase may
      play a role in restoring IFN-gamma secretions and subsequent antigen presentation
      in response to mycobacterial infection. In conclusion, our results suggest a
      significant role for GSK3 in guarding against mycobacterial evasion of immunity
      via IL-10 induction in the host.

PMID- 19401397
TI  - Intact extracellular matrix and the maintenance of immune tolerance: high
      molecular weight hyaluronan promotes persistence of induced CD4+CD25+ regulatory
      T cells.
AB  - The composition of the ECM provides contextual cues to leukocytes in inflamed and
      healing tissues. One example of this is HA, where LMW-HA, generated during active
      inflammation, is a TLR ligand and an endogenous "danger signal," and HMW-HA,
      predominant in healing or intact tissues, functions in an inverse manner. Our
      data suggest that HMW-HA actively promotes immune tolerance by augmenting
      CD4+CD25+ T(Reg) function, and LMW-HA does not. Using a human iT(Reg) model, we
      demonstrate that HMW-HA but not LMW-HA provides a costimulatory signal through
      cross-linking CD44 which promotes Foxp3 expression, a critical signaling molecule
      associated with T(Reg). This effect, in part, may be mediated by a role for
      intact HMW-HA in IL-2 production, as T(Reg) are highly IL-2-dependent for their
      survival and function. We propose that HMW-HA contributes to the maintenance of
      immune homeostasis in uninjured tissue and effectively communicates an "all
      clear" signal to down-regulate the adaptive immune system through T(Reg) after
      tissue matrix integrity has been restored.

PMID- 19401399
TI  - Affinity Density: a novel genomic approach to the identification of transcription
      factor regulatory targets.
AB  - METHODS: A new method was developed for identifying novel transcription factor
      regulatory targets based on calculating Local Affinity Density. Techniques from
      the signal-processing field were used, in particular the Hann digital filter, to
      calculate the relative binding affinity of different regions based on previously
      published in vitro binding data. To illustrate this approach, the complete
      genomes of Drosophila melanogaster and D.pseudoobscura were analyzed for binding
      sites of the homeodomain proteinc Tinman, an essential heart development gene in
      both Drosophila and Mouse. The significant binding regions were identified
      relative to genomic background and assigned to putative target genes. Valid
      candidates common to both species of Drosophila were selected as a test of
      conservation. RESULTS: The new method was more sensitive than cluster searches
      for conserved binding motifs with respect to positive identification of known
      Tinman targets. Our Local Affinity Density method also identified a significantly
      greater proportion of Tinman-coexpressed genes than equivalent, optimized cluster
      searching. In addition, this new method predicted a significantly greater than
      expected number of genes with previously published RNAi phenotypes in the heart.
      AVAILABILITY: Algorithms were implemented in Python, LISP, R and maxima, using
      MySQL to access locally mirrored sequence data from Ensembl (D.melanogaster
      release 4.3) and flybase (D.pseudoobscura). All code is licensed under GPL and
      freely available at http://www.ohsu.edu/cellbio/dev_biol_prog/affinitydensity/.

PMID- 19401398
TI  - Functional diversity for REST (NRSF) is defined by in vivo binding affinity
      hierarchies at the DNA sequence level.
AB  - The molecular events that contribute to, and result from, the in vivo binding of
      transcription factors to their cognate DNA sequence motifs in mammalian genomes
      are poorly understood. We demonstrate that variations within the DNA sequence
      motifs that bind the transcriptional repressor REST (NRSF) encode in vivo DNA
      binding affinity hierarchies that contribute to regulatory function during
      lineage-specific and developmental programs in fundamental ways. First, canonical
      sequence motifs for REST facilitate strong REST binding and control functional
      classes of REST targets that are common to all cell types, whilst atypical motifs
      participate in weak interactions and control those targets, which are cell- or
      tissue-specific. Second, variations in REST binding relate directly to variations
      in expression and chromatin configurations of REST's target genes. Third, REST
      clearance from its binding sites is also associated with variations in the RE1
      motif. Finally, and most surprisingly, weak REST binding sites reside in DNA
      sequences that show the highest levels of constraint through evolution, thus
      facilitating their roles in maintaining tissue-specific functions. These
      relationships have never been reported in mammalian systems for any transcription
      factor.

PMID- 19401400
TI  - List-decoding methods for inferring polynomials in finite dynamical gene network
      models.
AB  - MOTIVATION: The problem of reverse engineering the dynamics of gene expression
      profiles is of focal importance in systems biology. Due to noise and the inherent
      lack of sufficiently large datasets generated via high-throughput measurements,
      known reconstruction frameworks based on dynamical systems models fail to provide
      adequate settings for network analysis. This motivates the study of new
      approaches that produce stochastic lists of explanations for the observed network
      dynamics that can be efficiently inferred from small sample sets and in the
      presence of errors. RESULTS: We introduce a novel algebraic modeling framework,
      termed stochastic polynomial dynamical systems (SPDSs) that can capture the
      dynamics of regulatory networks based on microarray expression data. Here, we
      refer to dynamics of the network as the trajectories of gene expression profiles
      over time. The model assumes that the expression data is quantized in a manner
      that allows for imposing a finite field structure on the observations, and the
      existence of polynomial update functions for each gene in the network. The
      underlying reverse engineering algorithm is based on ideas borrowed from coding
      theory, and in particular, list-decoding methods for so called Reed-Muller codes.
      The list-decoding method was tested on synthetic data and on microarray
      expression measurements from the M(3D) database, corresponding to a subnetwork of
      the Escherichia coli SOS repair system, as well as on the complete transcription
      factor network, available at RegulonDB. The results show that SPDSs constructed
      via list-decoders significantly outperform other algebraic reverse engineering
      methods, and that they also provide good guidelines for estimating the influence
      of genes on the dynamics of the network. AVAILABILITY: Software codes for list
      decoding algorithms suitable for direct application to quantized expression data
      will be publicly available at the authors' web-pages.

PMID- 19401401
TI  - baobabLUNA: the solution space of sorting by reversals.
AB  - SUMMARY: Computing the reversal distance and searching for an optimal sequence of
      reversals to transform a unichromosomal genome into another are useful
      algorithmic tools to analyse real evolutionary scenarios. Currently, these
      problems can be solved by at least two available softwares, the prominent of
      which are GRAPPA and GRIMM. However, the number of different optimal sequences is
      usually huge and taking only the distance and/or one example is often
      insufficient to do a proper analysis. Here, we offer an alternative and present
      baobabLUNA, a framework that contains an algorithm to give a compact
      representation of the whole space of solutions for the sorting by reversals
      problem. AVAILABILITY AND IMPLEMENTATION: Compiled code implemented in Java is
      freely available for download at http://pbil.univ-lyon1.fr/software/luna/.
      Documentation with methodological background, technical aspects, download and
      setup instructions, interface description and tutorial are available at
      http://pbil.univ-lyon1.fr/software/luna/doc/luna-doc.pdf.

PMID- 19401402
TI  - Utilizing gene pair orientations for HMM-based analysis of promoter array ChIP
      chip data.
AB  - MOTIVATION: Array-based analysis of chromatin immunoprecipitation (ChIP-chip)
      data is a powerful technique for identifying DNA target regions of individual
      transcription factors. The identification of these target regions from
      comprehensive promoter array ChIP-chip data is challenging. Here, three
      approaches for the identification of transcription factor target genes from
      promoter array ChIP-chip data are presented. We compare (i) a standard log-fold
      change analysis (LFC); (ii) a basic method based on a Hidden Markov Model (HMM);
      and (iii) a new extension of the HMM approach to an HMM with scaled transition
      matrices (SHMM) that incorporates information about the relative orientation of
      adjacent gene pairs on DNA. RESULTS: All three methods are applied to different
      promoter array ChIP-chip datasets of the yeast Saccharomyces cerevisiae and the
      important model plant Arabidopsis thaliana to compare the prediction of
      transcription factor target genes. In the context of the yeast cell cycle, common
      target genes bound by the transcription factors ACE2 and SWI5, and ACE2 and FKH2
      are identified and evaluated using the Saccharomyces Genome Database. Regarding
      A.thaliana, target genes of the seed-specific transcription factor ABI3 are
      predicted and evaluate based on publicly available gene expression profiles and
      transient assays performed in the wet laboratory experiments. The application of
      the novel SHMM to these two different promoter array ChIP-chip datasets leads to
      an improved identification of transcription factor target genes in comparison to
      the two standard approaches LFC and HMM. AVAILABILITY: The software of LFC, HMM
      and SHMM, the ABI3 ChIP-chip dataset, and Supplementary Material can be
      downloaded from http://dig.ipk-gatersleben.de/SHMMs/ChIPchip/ChIPchip.html.

PMID- 19401403
TI  - Equine thrombospondin II and secreted protein acidic and cysteine-rich in a model
      of normal and pathological wound repair.
AB  - Wound healing in horses is complicated, particularly when wounds are on the limb.
      The objectives of this study were to clone equine thrombospondin II (THBS2) and
      secreted protein acidic and cysteine-rich (SPARC) cDNAs and to compare the
      spatiotemporal expression of mRNAs and proteins during repair of body and limb
      wounds. These molecules were targeted in view of their potential biological
      contribution to angiogenesis, which is exacerbated during the repair of limb
      wounds in horses. Cloning was achieved by screening size-selected cDNA libraries
      previously derived from 7-day-old wounds. Expression was studied in unwounded
      skin and in samples from 1, 2, 3, 4, and 6 wk old wounds of the body and limb.
      Temporal gene expression was determined by semiquantitative RT-PCR, while protein
      expression was mapped immunohistochemically. The temporal pattern of expression
      for both genes was similar; wounding caused immediate upregulation of mRNA, which
      did not return to baseline by the end of the study, and overexpression was noted
      in body relative to limb wounds. Immunostaining for THBS2 and SPARC was induced
      by wounding, though no differences in stain location or intensity were detected
      between body and limb wounds. This study is the first to characterize equine cDNA
      for THBS2 and SPARC and to document mRNA expression over the different phases of
      repair. THBS2 and SPARC might modulate angiogenesis during wound healing in the
      horse, which could protect against the disproportionate fibroplasia commonly
      afflicting limb wounds and leading to the development of exuberant granulation
      tissue.

PMID- 19401404
TI  - Individual molecular response to elevated intraocular pressure in perfused
      postmortem human eyes.
AB  - Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. In the
      clinic, the response to elevated pressure and thus the risk for development of
      glaucoma differs among individuals. We took advantage of our ability to subject
      postmortem human eyes from the same individual to physiological and elevated
      pressure in a perfused outflow model and compared individual patterns of gene
      expression under pressure. The architecture of the trabecular meshwork, tissue
      responsible for the maintenance of IOP, was conserved. We performed two sets of
      experiments. The first set (n = 5, 10 eyes) used Affymetrix GeneChips, identified
      the 20 most pressure-altered genes in each individual, and compared their
      pressure response in the other four. The second set (n = 5, 10 eyes) selected 21
      relevant trabecular meshwork genes and examined, by real-time TaqMan-PCR, the
      rank of their abundance and of their pressure differential expression in each
      individual. The majority of the up- and downregulated top-changers of each
      individual showed an individual response trend. Few genes were general
      responders. Individual responders included STATH, FBN2, TF, OGN, IL6, IGF1,
      CRYAB, and ELAM1 (marker for glaucoma). General responders included MMP1, MMP10,
      CXCL2, and PDPN. In addition, we found that although the relative abundance of
      selected genes was very similar among nonstressed individuals, the response to
      pressure of those same genes had a marked individual component. Our results offer
      the first molecular insight on the variation of the individual response to IOP
      observed in the clinical setting.

PMID- 19401405
TI  - Severe pneumonia in Mozambican young children: clinical and radiological
      characteristics and risk factors.
AB  - BACKGROUND: Pneumonia is a leading cause of hospitalization and death among
      children in Africa. We describe the clinical presentation of severe pneumonia
      among hospitalized children in a malaria endemic area with a high prevalence of
      HIV infection. METHODS: As part of a 2-year prospective study of radiologically
      confirmed pneumonia, chest radiographs, malaria parasite counts and bacterial
      blood cultures were systematically performed for children 0-23 months admitted
      with severe pneumonia. Radiographs were interpreted according to WHO guidelines.
      HIV tests were performed during a 12-month period. RESULTS: Severe pneumonia
      accounted for 16% of 4838 hospital admissions among children 0-23 months; 43% of
      episodes had endpoint consolidation, 15% were associated with bacteremia and 11%
      were fatal. Fever, cough >3 days, crepitations, hypoxemia and absence of malaria
      parasitemia were associated with radiologically confirmed pneumonia. Nineteen per
      cent of children with severe pneumonia and 27% with radiologically confirmed
      pneumonia had clinical malaria. HIV-prevalence was 26% among children
      hospitalized with severe pneumonia and HIV-testing results. HIV infection,
      anaemia, malnutrition, hypoxemia and bacteremia were associated with fatal
      episodes of severe pneumonia. CONCLUSION: Treatment of admitted children with
      severe pneumonia is complicated in settings with prevalent HIV and malaria.
      Children with severe pneumonia and clinical malaria require antibiotic and
      antimalarial treatment. In addition to vertical programs, integrated approaches
      may greatly contribute to reduction of pneumonia-related mortality.

PMID- 19401406
TI  - Coagulation status and platelet functions in children with severe falciparum
      malaria and their correlation of outcome.
AB  - This study was undertaken to observe the changes in coagulation and platelet
      profile, and findings were correlated with their outcome. Forty consecutive
      children with severe falciparum malaria were studied for their coagulation
      status, i.e. prothrombin time (PT), activated thromboplastin time (APTT),
      thrombin time (TT) and anti-thrombin-III (AT-III), platelet profile (platelet
      count, platelet aggregation with adenine diphosphate (ADP) and ADR and PF3
      availability). Derangements in the coagulation profile in the form of increased
      PT, APTT and/or TT were seen in 47.5, 35 and 62.5% cases, respectively, but
      bleeding was seen in only six cases. Thrombocytopenia was found in 34 patients.
      Platelet aggregation with ADP and ADR revealed hypoaggregation in 95.3 and 97.5%
      cases, respectively, and were statistically significant. Platelet factor-3
      availability was also significantly prolonged. Patients with prolonged PT, PF-3
      and hypoaggregation with adrenaline had 1.4, 1.7 and 1.45 times higher risk of
      mortality.

PMID- 19401407
TI  - Screening of 18-24-month-old children for autism in a semi-urban community in Sri
      Lanka.
AB  - All children aged 18-24 months in a defined geographical area were initially
      screened for autism, using 'Red Flag' criteria. All the children with one or more
      positive 'Red Flag' signs were further screened using Modified Checklist for
      Autism in Toddlers (M-CHAT) translated to Sinhala, followed by a comprehensive
      clinical assessment. Of a sample of 374 children, 'Red Flag' signs were positive
      in 28 (7.4%). Four children received a diagnosis of autism on clinical assessment
      giving a prevalence of 1.07% or 1 per 93 in the 18-24-month age group.
      Sensitivity of M-CHAT was only 25%, and specificity 70%. The high prevalence
      detected strongly justifies early community-based screening, but a culturally
      sensitive screening tool needs to be developed for Sri Lanka.

PMID- 19401408
TI  - Human bocavirus in very young infants hospitalized with acute respiratory
      infection in northeast Brazil.
AB  - A cross-sectional study was carried out over a period of 12 months to investigate
      the occurrence of human bocavirus (HBoV) infection in infants hospitalized for
      respiratory infections in a teaching hospital in Salvador, Brazil, and to
      describe the clinical manifestations of this infection. Nasopharyngeal aspirates
      were collected from the children and immunofluorescence and polymerase chain
      reaction were performed to investigate the presence of respiratory viruses. HBoV
      was detected in 4 out of 66 patients. Two of the HBoV-positive infants were co
      infected with other viruses. The principal clinical findings in HBoV-positive
      children were: nasal obstruction, catarrh, cough, fever and dyspnea. This study
      revealed HBoV infection in children aged <2 months, suggesting that the infection
      may occur at a very early age.

PMID- 19401409
TI  - Root-to-shoot Cd translocation via the xylem is the major process determining
      shoot and grain cadmium accumulation in rice.
AB  - Physiological properties involved in divergent cadmium (Cd) accumulation among
      rice genotypes were characterized using the indica cultivar 'Habataki' (high Cd
      in grains) and the japonica cultivar 'Sasanishiki' (low Cd in grains). Time
      dependence and concentration-dependence of symplastic Cd absorption in roots were
      revealed not to be responsible for the different Cd accumulation between the two
      cultivars because root Cd uptake was not greater in the Cd-accumulating cultivar
      'Habataki' compared with 'Sasanishiki'. On the other hand, rapid and greater root
      to-shoot Cd translocation was observed in 'Habataki', which could be mediated by
      higher abilities in xylem loading of Cd and transpiration rate as a driving
      force. To verify whether different abilities in xylem-mediated shoot-to-root
      translocation generally account for the genotypic variation in shoot Cd
      accumulation in rice, the world rice core collection, consisting of 69 accessions
      which covers the genetic diversity of almost 32,000 accessions of cultivated
      rice, was used. The results showed strong correlation between Cd levels in xylem
      sap and shoots and grains among the 69 rice accessions. Overall, the results
      presented in this study revealed that the root-to-shoot Cd translocation via the
      xylem is the major and common physiological process determining the Cd
      accumulation level in shoots and grains of rice plants.

PMID- 19401410
TI  - The effect of sucrose and abscisic acid interaction on sucrose synthase and its
      relationship to grain filling of rice (Oryza sativa L.).
AB  - Rice grain filling is a process of conversion of sucrose into starch catalysed by
      a series of enzymes. Sucrose synthase (SUS) is considered as a key enzyme
      regulating this process. This study investigated the possible roles of sucrose
      and abscisic acid (ABA) in mediating the activity and expression of SUS protein
      of grains during grain filling in rice (Oryza sativa). Field-grown rice plants
      and detached cultured panicles were used as experimental materials. Several
      treatments, including spikelet thinning, leaf cutting, and applications of
      different concentrations of exogenous sucrose and ABA, were imposed during grain
      filling. A higher SUS activity was found in superior grains than in inferior
      grains in the earlier stage of grain filling, which was significantly and closely
      related to a higher grain filling rate and starch accumulation. An increase in
      sucrose concentration in grains as a result of different treatments increased
      both SUS activity and SUS protein expression in grains. An increase in ABA
      concentration gave similar results. Furthermore, effects of interactions between
      sucrose and ABA on the activity and expression of SUS protein in grains were also
      found. It was suggested that sucrose- and ABA-mediated rice grain filling is
      largely due to an increase in SUS activity and SUS protein expression.

PMID- 19401411
TI  - 13C and 15N allocations of two alpine species from early and late snowmelt
      locations reflect their different growth strategies.
AB  - Intense efforts are currently devoted to disentangling the relationships between
      plant carbon (C) allocation patterns and soil nitrogen (N) availability because
      of their consequences for growth and more generally for C sequestration. In cold
      ecosystems, only a few studies have addressed whole-plant C and/or N allocation
      along natural elevational or topographical gradients. (12)C/(13)C and (14)N/(15)N
      isotope techniques have been used to elucidate C and N partitioning in two alpine
      graminoids characterized by contrasted nutrient economies: a slow-growing
      species, Kobresia myosuroides (KM), and a fast-growing species, Carex foetida
      (CF), located in early and late snowmelt habitats, respectively, within the
      alpine tundra (French Alps). CF allocated higher labelling-related (13)C content
      belowground and produced more root biomass. Furthermore, assimilates transferred
      to the roots were preferentially used for growth rather than respiration and
      tended to favour N reduction in this compartment. Accordingly, this species had
      higher (15)N uptake efficiency than KM and a higher translocation of reduced
      (15)N to aboveground organs. These results suggest that at the whole-plant level,
      there is a compromise between N acquisition/reduction and C allocation patterns
      for optimized growth.

PMID- 19401412
TI  - Elevated CO2 effects on plant carbon, nitrogen, and water relations: six
      important lessons from FACE.
AB  - Plant responses to the projected future levels of CO(2) were first characterized
      in short-term experiments lasting days to weeks. However, longer term acclimation
      responses to elevated CO(2) were subsequently discovered to be very important in
      determining plant and ecosystem function. Free-Air CO(2) Enrichment (FACE)
      experiments are the culmination of efforts to assess the impact of elevated CO(2)
      on plants over multiple seasons and, in the case of crops, over their entire
      lifetime. FACE has been used to expose vegetation to elevated concentrations of
      atmospheric CO(2) under completely open-air conditions for nearly two decades.
      This review describes some of the lessons learned from the long-term investment
      in these experiments. First, elevated CO(2) stimulates photosynthetic carbon gain
      and net primary production over the long term despite down-regulation of Rubisco
      activity. Second, elevated CO(2) improves nitrogen use efficiency and, third,
      decreases water use at both the leaf and canopy scale. Fourth, elevated CO(2)
      stimulates dark respiration via a transcriptional reprogramming of metabolism.
      Fifth, elevated CO(2) does not directly stimulate C(4) photosynthesis, but can
      indirectly stimulate carbon gain in times and places of drought. Finally, the
      stimulation of yield by elevated CO(2) in crop species is much smaller than
      expected. While many of these lessons have been most clearly demonstrated in crop
      systems, all of the lessons have important implications for natural systems.

PMID- 19401413
TI  - MUM ENHANCERS are important for seed coat mucilage production and mucilage
      secretory cell differentiation in Arabidopsis thaliana.
AB  - Pollination triggers not only embryo development but also the differentiation of
      the ovule integuments to form a specialized seed coat. The mucilage secretory
      cells of the Arabidopsis thaliana seed coat undergo a complex differentiation
      process in which cell growth is followed by the synthesis and secretion of
      pectinaceous mucilage. A number of genes have been identified affecting mucilage
      secretory cell differentiation, including MUCILAGE-MODIFIED4 (MUM4). mum4 mutants
      produce a reduced amount of mucilage and cloning of MUM4 revealed that it encodes
      a UDP-L-rhamnose synthase that is developmentally up-regulated to provide
      rhamnose for mucilage pectin synthesis. To identify additional genes acting in
      mucilage synthesis and secretion, a screen for enhancers of the mum4 phenotype
      was performed. Eight mum enhancers (men) have been identified, two of which
      result from defects in known mucilage secretory cell genes (MUM2 and MYB61). Our
      results show that, in a mum4 background, mutations in MEN1, MEN4, and MEN5 lead
      to further reductions in mucilage compared to mum4 single mutants, suggesting
      that they are involved in mucilage synthesis or secretion. Conversely, mutations
      in MEN2 and MEN6 appear to affect mucilage release rather than quantity. With the
      exception of men4, whose single mutant exhibits reduced mucilage, none of these
      genes have a single mutant phenotype, suggesting that they would not have been
      identified outside the compromised mum4 background.

PMID- 19401415
TI  - Deletion of PKCepsilon selectively enhances the amplifying pathways of glucose
      stimulated insulin secretion via increased lipolysis in mouse beta-cells.
AB  - OBJECTIVE: Insufficient insulin secretion is a hallmark of type 2 diabetes, and
      exposure of beta-cells to elevated lipid levels (lipotoxicity) contributes to
      secretory dysfunction. Functional ablation of protein kinase C epsilon
      (PKCepsilon) has been shown to improve glucose homeostasis in models of type 2
      diabetes and, in particular, to enhance glucose-stimulated insulin secretion
      (GSIS) after lipid exposure. Therefore, we investigated the lipid-dependent
      mechanisms responsible for the enhanced GSIS after inactivation of PKCepsilon.
      RESEARCH DESIGN AND METHODS: We cultured islets isolated from PKCepsilon knockout
      (PKCepsilonKO) mice in palmitate prior to measuring GSIS, Ca(2+) responses,
      palmitate esterification products, lipolysis, lipase activity, and gene
      expression. RESULTS: The enhanced GSIS could not be explained by increased
      expression of another PKC isoform or by alterations in glucose-stimulated Ca(2+)
      influx. Instead, an upregulation of the amplifying pathways of GSIS in lipid
      cultured PKCepsilonKO beta-cells was revealed under conditions in which
      functional ATP-sensitive K(+) channels were bypassed. Furthermore, we showed
      increased esterification of palmitate into triglyceride pools and an enhanced
      rate of lipolysis and triglyceride lipase activity in PKCepsilonKO islets. Acute
      treatment with the lipase inhibitor orlistat blocked the enhancement of GSIS in
      lipid-cultured PKCepsilonKO islets, suggesting that a lipolytic product mediates
      the enhancement of glucose-amplified insulin secretion after PKCepsilon deletion.
      CONCLUSIONS: Our findings demonstrate a mechanistic link between lipolysis and
      the amplifying pathways of GSIS in murine beta-cells, and they suggest an
      interaction between PKCepsilon and lipolysis. These results further highlight the
      therapeutic potential of PKCepsilon inhibition to enhance GSIS from the beta-cell
      under conditions of lipid excess.

PMID- 19401414
TI  - Confirmation of multiple risk Loci and genetic impacts by a genome-wide
      association study of type 2 diabetes in the Japanese population.
AB  - OBJECTIVE: To identify novel type 2 diabetes gene variants and confirm previously
      identified ones, a three-staged genome-wide association study was performed in
      the Japanese population. RESEARCH DESIGN AND METHODS: In the stage 1 scan, we
      genotyped 519 case and 503 control subjects with 482,625 single nucleotide
      polymorphism (SNP) markers; in the stage 2 panel comprising 1,110 case subjects
      and 1,014 control subjects, we assessed 1,456 SNPs (P < 0.0025, stage 1);
      additionally to direct genotyping, 964 healthy control subjects formed the in
      silico control panel. Along with genome-wide exploration, we aimed to replicate
      the disease association of 17 SNPs from 16 candidate loci previously identified
      in Europeans. The associated and/or replicated loci (23 SNPs; P < 7 x 10(-5) for
      genome-wide exploration and P < 0.05 for replication) were examined in the stage
      3 panel comprising 4,000 case subjects and 12,569 population-based samples, from
      which 4,889 nondiabetic control subjects were preselected. The 12,569 subjects
      were used for overall risk assessment in the general population. RESULTS: Four
      loci-1 novel with suggestive evidence (PEPD on 19q13, P = 1.4 x 10(-5)) and three
      previously reported-were identified; the association of CDKAL1, CDKN2A/CDKN2B,
      and KCNQ1 were confirmed (P < 10(-19)). Moreover, significant associations were
      replicated in five other candidate loci: TCF7L2, IGF2BP2, SLC30A8, HHEX, and
      KCNJ11. There was substantial overlap of type 2 diabetes susceptibility genes
      between the two populations, whereas effect size and explained variance tended to
      be higher in the Japanese population. CONCLUSIONS: The strength of association
      was more prominent in the Japanese population than in Europeans for more than
      half of the confirmed type 2 diabetes loci.

PMID- 19401416
TI  - The presence and severity of chronic kidney disease predicts all-cause mortality
      in type 1 diabetes.
AB  - OBJECTIVES: This study aimed to identify clinical features associated with
      premature mortality in a large contemporary cohort of adults with type 1
      diabetes. RESEARCH DESIGN AND METHODS: The Finnish Diabetic Nephropathy
      (FinnDiane) study is a national multicenter prospective follow-up study of 4,201
      adults with type 1 diabetes from 21 university and central hospitals, 33 district
      hospitals, and 26 primary health care centers across Finland. RESULTS: During a
      median 7 years of follow-up, there were 291 deaths (7%), 3.6-fold (95% CI 3.2
      4.0) more than that observed in the age- and sex-matched general population.
      Excess mortality was only observed in individuals with chronic kidney disease.
      Individuals with normoalbuminuria showed no excess mortality beyond the general
      population (standardized mortality ratio [SMR] 0.8, 95% CI 0.5-1.1), independent
      of the duration of diabetes. The presence of microalbuminuria, macroalbuminuria,
      and end-stage kidney disease was associated with 2.8, 9.2, and 18.3 times higher
      SMR, respectively. The increase in mortality across each stage of albuminuria was
      equivalent to the risk conferred by preexisting macrovascular disease. In
      addition, the glomerular filtration rate was independently associated with
      mortality, such that individuals with impaired kidney function, as well as those
      demonstrating hyperfiltration, had an increased risk of death. CONCLUSIONS: An
      independent graded association was observed between the presence and severity of
      kidney disease and mortality in a large contemporary cohort of individuals with
      type 1 diabetes. These findings highlight the clinical and public health
      importance of chronic kidney disease and its prevention in the management of type
      1 diabetes.

PMID- 19401417
TI  - The transforming growth factor-beta pathway is a common target of drugs that
      prevent experimental diabetic retinopathy.
AB  - OBJECTIVE: Prevention of diabetic retinopathy would benefit from availability of
      drugs that preempt the effects of hyperglycemia on retinal vessels. We aimed to
      identify candidate drug targets by investigating the molecular effects of drugs
      that prevent retinal capillary demise in the diabetic rat. RESEARCH DESIGN AND
      METHODS: We examined the gene expression profile of retinal vessels isolated from
      rats with 6 months of streptozotocin-induced diabetes and compared it with that
      of control rats. We then tested whether the aldose reductase inhibitor sorbinil
      and aspirin, which have different mechanisms of action, prevented common
      molecular abnormalities induced by diabetes. The Affymetrix GeneChip Rat Genome
      230 2.0 array was complemented by real-time RT-PCR, immunoblotting, and
      immunohistochemistry. RESULTS: The retinal vessels of diabetic rats showed
      differential expression of 20 genes of the transforming growth factor (TGF)-beta
      pathway, in addition to genes involved in oxidative stress, inflammation,
      vascular remodeling, and apoptosis. The complete loop of TGF-beta signaling,
      including Smad2 phosphorylation, was enhanced in the retinal vessels, but not in
      the neural retina. Sorbinil normalized the expression of 71% of the genes related
      to oxidative stress and 62% of those related to inflammation. Aspirin had minimal
      or no effect on these two categories. The two drugs were instead concordant in
      reducing the upregulation of genes of the TGF-beta pathway (55% for sorbinil and
      40% for aspirin) and apoptosis (74 and 42%, respectively). CONCLUSIONS: Oxidative
      and inflammatory stress is the distinct signature that the polyol pathway leaves
      on retinal vessels. TGF-beta and apoptosis are, however, the ultimate targets to
      prevent the capillary demise in diabetic retinopathy.

PMID- 19401418
TI  - Enhanced glucose tolerance by SK4 channel inhibition in pancreatic beta-cells.
AB  - OBJECTIVE: Ca(2+)-regulated K(+) channels are involved in numerous Ca(2+)
      dependent signaling pathways. In this study, we investigated whether the Ca(2+)
      activated K(+) channel of intermediate conductance SK4 (KCa3.1, IK1) plays a
      physiological role in pancreatic beta-cell function. RESEARCH DESIGN AND METHODS:
      Glucose tolerance and insulin sensitivity were determined in wild-type (WT) or
      SK4 knockout (SK4-KO) mice. Electrophysiological experiments were performed with
      the patch-clamp technique. The cytosolic Ca(2+) concentration ([Ca(2+)](c)) was
      determined by fura-2 fluorescence. Insulin release was assessed by
      radioimmunoassay, and SK4 protein was detected by Western blot analysis. RESULTS:
      SK4-KO mice showed improved glucose tolerance, whereas insulin sensitivity was
      not altered. The animals were not hypoglycemic. Isolated SK4-KO beta-cells
      stimulated with 15 mmol/l glucose had an increased Ca(2+) action potential
      frequency, and single-action potentials were broadened. These alterations were
      coupled to increased [Ca(2+)](c). In addition, glucose responsiveness of membrane
      potential, [Ca(2+)](c), and insulin secretion were shifted to lower glucose
      concentrations. SK4 protein was expressed in WT islets. An increase in K(+)
      currents and concomitant membrane hyperpolarization could be evoked in WT beta
      cells by the SK4 channel opener DCEBIO (100 micromol/l). Accordingly, the SK4
      channel blocker TRAM-34 (1 micromol/l) partly inhibited K(Ca) currents and
      induced electrical activity at a threshold glucose concentration. In stimulated
      WT beta-cells, TRAM-34 further increased [Ca(2+)](c) and broadened action
      potentials similar to those seen in SK4-KO beta-cells. SK4 channels were found to
      substantially contribute to K(slow) (slowly activating K(+) current).
      CONCLUSIONS: SK4 channels are involved in beta-cell stimulus-secretion coupling.
      Deficiency of SK4 current induces elevated beta-cell responsiveness and coincides
      with improved glucose tolerance in vivo. Therefore, pharmacologic modulation of
      these channels might provide an interesting approach for the development of novel
      insulinotropic drugs.

PMID- 19401419
TI  - Common variation in SIM1 is reproducibly associated with BMI in Pima Indians.
AB  - OBJECTIVE: Haploinsufficiency of SIM1 is a cause of rare monogenic obesity. To
      assess the role of SIM1 in polygenic obesity, this gene was analyzed in the Pima
      Indian population, which has a high prevalence of obesity. RESEARCH DESIGN AND
      METHODS: SIM1 was sequenced in 96 individuals. Variants (n = 46) were genotyped
      in a population-based sample of 3,250 full-heritage Pima Indians and in a
      separate replication sample of 2,944 predominately non-full-heritage subjects
      from the same community. RESULTS: Variants spanning the upstream region of SIM1
      through intron 8 were associated with BMI in the full-heritage Pima Indians,
      where the strongest associations (P approximately 10(-4) to 10(-6)) were with
      common variants (risk allele frequency 0.61-0.67). The difference in mean BMI
      between individuals homozygous for the major allele compared with homozygotes for
      the minor allele was approximately 2.2 kg/m(2) (P = 2 x 10(-5) for rs3213541).
      These associations replicated in the separate sample of subjects from the same
      community (P = 5 x 10(-3) for rs3213541). The strongest associations (P = 4 x 10(
      7), controlled for age, sex, birth year, and heritage) were seen in the combined
      sample (n = 6,194). The risk allele for obesity was more common in full-heritage
      Pimas than in the mixed-heritage subjects. Two variants (rs3734353 and rs3213541)
      were also genotyped in 1,275 severely obese and 1,395 lean control subjects of
      French European ancestry. The Pima risk alleles were the minor alleles in the
      European samples, and these variants did not display any significant association
      (P > 0.05). CONCLUSIONS: Common variation in SIM1 is associated with BMI on a
      population level in Pima Indians where the risk allele is the major allele.

PMID- 19401420
TI  - Inhibitory effects of leptin on pancreatic alpha-cell function.
AB  - OBJECTIVE: Leptin released from adipocytes plays a key role in the control of
      food intake, energy balance, and glucose homeostasis. In addition to its central
      action, leptin directly affects pancreatic beta-cells, inhibiting insulin
      secretion, and, thus, modulating glucose homeostasis. However, despite the
      importance of glucagon secretion in glucose homeostasis, the role of leptin in
      alpha-cell function has not been studied in detail. In the present study, we have
      investigated this functional interaction. RESEARCH DESIGN AND METHODS: The
      presence of leptin receptors (ObR) was demonstrated by RT-PCR analysis, Western
      blot, and immunocytochemistry. Electrical activity was analyzed by patch-clamp
      and Ca(2+) signals by confocal microscopy. Exocytosis and glucagon secretion were
      assessed using fluorescence methods and radioimmunoassay, respectively. RESULTS:
      The expression of several ObR isoforms (a-e) was detected in glucagon-secreting
      alphaTC1-9 cells. ObRb, the main isoform involved in leptin signaling, was
      identified at the protein level in alphaTC1-9 cells as well as in mouse and human
      alpha-cells. The application of leptin (6.25 nmol/l) hyperpolarized the alpha
      cell membrane potential, suppressing the electrical activity induced by 0.5
      mmol/l glucose. Additionally, leptin inhibited Ca(2+) signaling in alphaTC1-9
      cells and in mouse and human alpha-cells within intact islets. A similar result
      occurred with 0.625 nmol/l leptin. These effects were accompanied by a decrease
      in glucagon secretion from mouse islets and were counteracted by the
      phosphatidylinositol 3-kinase inhibitor, wortmannin, suggesting the involvement
      of this pathway in leptin action. CONCLUSIONS: These results demonstrate that
      leptin inhibits alpha-cell function, and, thus, these cells are involved in the
      adipoinsular communication.

PMID- 19401421
TI  - Diabetes-specific HLA-DR-restricted proinflammatory T-cell response to wheat
      polypeptides in tissue transglutaminase antibody-negative patients with type 1
      diabetes.
AB  - OBJECTIVE: There is evidence of gut barrier and immune system dysfunction in some
      patients with type 1 diabetes, possibly linked with exposure to dietary wheat
      polypeptides (WP). However, questions arise regarding the frequency of abnormal
      immune responses to wheat and their nature, and it remains unclear whether such
      responses are diabetes specific. RESEARCH DESIGN AND METHODS: In type 1 diabetic
      patients and healthy control subjects, the immune response of peripheral CD3(+) T
      cells to WPs, ovalbumin, gliadin, alpha-gliadin 33-mer peptide, tetanus toxoid,
      and phytohemagglutinin was measured using a carboxyfluorescein diacetate
      succinimidyl ester (CFSE) proliferation assay. T-helper cell type 1 (Th1), Th2,
      and Th17 cytokines were analyzed in WP-stimulated peripheral blood mononuclear
      cell (PBMNC) supernatants, and HLA was analyzed by PCR. RESULTS: Of 42 patients,
      20 displayed increased CD3(+) T-cell proliferation to WPs and were classified as
      responders; proliferative responses to other dietary antigens were less
      pronounced. WP-stimulated PBMNCs from patients showed a mixed proinflammatory
      cytokine response with large amounts of IFN-gamma, IL-17A, and increased TNF. HLA
      DQ2, the major celiac disease risk gene, was not significantly different. Nearly
      all responders carried the diabetes risk gene HLA-DR4. Anti-DR antibodies blocked
      the WP response and inhibited secretion of Th1 and Th17 cytokines. High amounts
      of WP-stimulated IL-6 were not blocked. CONCLUSIONS: T-cell reactivity to WPs was
      frequently present in type 1 diabetic patients and associated with HLA-DR4 but
      not HLA-DQ2. The presence of an HLA-DR-restricted Th1 and Th17 response to WPs in
      a subset of patients indicates a diabetes-related inflammatory state in the gut
      immune tissues associated with defective oral tolerance and possibly gut barrier
      dysfunction.

PMID- 19401423
TI  - Free fatty acids link metabolism and regulation of the insulin-sensitizing
      fibroblast growth factor-21.
AB  - OBJECTIVE: Fibroblast growth factor (FGF)-21 improves insulin sensitivity and
      lipid metabolism in obese or diabetic animal models, while human studies revealed
      increased FGF-21 levels in obesity and type 2 diabetes. Given that FGF-21 has
      been suggested to be a peroxisome proliferator-activator receptor (PPAR) alpha
      dependent regulator of fasting metabolism, we hypothesized that free fatty acids
      (FFAs), natural agonists of PPARalpha, might modify FGF-21 levels. RESEARCH
      DESIGN AND METHODS: The effect of fatty acids on FGF-21 was investigated in vitro
      in HepG2 cells. Within a randomized controlled trial, the effects of elevated
      FFAs were studied in 21 healthy subjects (13 women and 8 men). Within a clinical
      trial including 17 individuals, the effect of insulin was analyzed using an
      hyperinsulinemic-euglycemic clamp and the effect of PPARgamma activation was
      studied subsequently in a rosiglitazone treatment trial over 8 weeks. RESULTS:
      Oleate and linoleate increased FGF-21 expression and secretion in a PPARalpha
      dependent fashion, as demonstrated by small-interfering RNA-induced PPARalpha
      knockdown, while palmitate had no effect. In vivo, lipid infusion induced an
      increase of circulating FGF-21 in humans, and a strong correlation between the
      change in FGF-21 levels and the change in FFAs was observed. An artificial
      hyperinsulinemia, which was induced to delineate the potential interaction
      between elevated FFAs and hyperinsulinemia, revealed that hyperinsulinemia also
      increased FGF-21 levels in vivo, while rosiglitazone treatment had no effect.
      CONCLUSIONS: The results presented here offer a mechanism explaining the
      induction of the metabolic regulator FGF-21 in the fasting situation but also in
      type 2 diabetes and obesity.

PMID- 19401422
TI  - Macrophages and adipocytes in human obesity: adipose tissue gene expression and
      insulin sensitivity during calorie restriction and weight stabilization.
AB  - OBJECTIVE: We investigated the regulation of adipose tissue gene expression
      during different phases of a dietary weight loss program and its relation with
      insulin sensitivity. RESEARCH DESIGN AND METHODS: Twenty-two obese women followed
      a dietary intervention program composed of an energy restriction phase with a 4
      week very-low-calorie diet and a weight stabilization period composed of a 2
      month low-calorie diet followed by 3-4 months of a weight maintenance diet. At
      each time point, a euglycemic-hyperinsulinemic clamp and subcutaneous adipose
      tissue biopsies were performed. Adipose tissue gene expression profiling was
      performed using a DNA microarray in a subgroup of eight women. RT-quantitative
      PCR was used for determination of mRNA levels of 31 adipose tissue macrophage
      markers (n = 22). RESULTS: Body weight, fat mass, and C-reactive protein level
      decreased and glucose disposal rate increased during the dietary intervention
      program. Transcriptome profiling revealed two main patterns of variations. The
      first involved 464 mostly adipocyte genes involved in metabolism that were
      downregulated during energy restriction, upregulated during weight stabilization,
      and unchanged during the dietary intervention. The second comprised 511 mainly
      macrophage genes involved in inflammatory pathways that were not changed or
      upregulated during energy restriction and downregulated during weight
      stabilization and dietary intervention. Accordingly, macrophage markers were
      upregulated during energy restriction and downregulated during weight
      stabilization and dietary intervention. The increase in glucose disposal rates in
      each dietary phase was associated with variation in expression of sets of 80-110
      genes that differed among energy restriction, weight stabilization, and dietary
      intervention. CONCLUSIONS: Adipose tissue macrophages and adipocytes show
      distinct patterns of gene regulation and association with insulin sensitivity
      during the various phases of a dietary weight loss program.

PMID- 19401424
TI  - Lack of type VIII collagen in mice ameliorates diabetic nephropathy.
AB  - OBJECTIVE: Key features of diabetic nephropathy include the accumulation of
      extracellular matrix proteins. In recent studies, increased expression of type
      VIII collagen in the glomeruli and tubulointerstitium of diabetic kidneys has
      been noted. The objectives of this study were to assess whether type VIII
      collagen affects the development of diabetic nephropathy and to determine type
      VIII collagen-dependent pathways in diabetic nephropathy in the mouse model of
      streptozotocin (STZ)-induced diabetes. RESEARCH DESIGN AND METHODS: Diabetes was
      induced by STZ injections in collagen VIII-deficient or wild-type mice.
      Functional and histological analyses were performed 40 days after induction of
      diabetes. Type VIII collagen expression was assessed by Northern blots,
      immunohistochemistry, and real-time PCR. Proliferation of primary mesangial cells
      was measured by thymidine incorporation and direct cell counting. Expression of
      phosphorylated extracellular signal-regulated kinase (ERK1/2) and p27(Kip1) was
      assessed by Western blots. Finally, Col8a1 was stably overexpressed in mesangial
      cells. RESULTS: Diabetic wild-type mice showed a strong renal induction of type
      VIII collagen. Diabetic Col8a1(-)/Col8a2(-) animals revealed reduced mesangial
      expansion and cellularity and extracellular matrix expansion compared with the
      wild type. These were associated with less albuminuria. High-glucose medium as
      well as various cytokines induced Col8a1 in cultured mesangial cells. Col8a1(
      )/Col8a2(-) mesangial cells revealed decreased proliferation, less
      phosphorylation of Erk1/2, and increased p27(Kip1) expression. Overexpression of
      Col8a1 in mesangial cells induced proliferation. CONCLUSIONS: Lack of type VIII
      collagen confers renoprotection in diabetic nephropathy. One possible mechanism
      is that type VIII collagen permits and/or fosters mesangial cell proliferation in
      early diabetic nephropathy.

PMID- 19401425
TI  - Glucagon-like peptide-1 protects beta-cells against apoptosis by increasing the
      activity of an IGF-2/IGF-1 receptor autocrine loop.
AB  - OBJECTIVE: The gluco-incretin hormones glucagon-like peptide (GLP)-1 and gastric
      inhibitory peptide (GIP) protect beta-cells against cytokine-induced apoptosis.
      Their action is initiated by binding to specific receptors that activate the cAMP
      signaling pathway, but the downstream events are not fully elucidated. Here we
      searched for mechanisms that may underlie this protective effect. RESEARCH DESIGN
      AND METHODS: We performed comparative transcriptomic analysis of islets from
      control and GipR(-/-);Glp-1-R(-/-) mice, which have increased sensitivity to
      cytokine-induced apoptosis. We found that IGF-1 receptor expression was markedly
      reduced in the mutant islets. Because the IGF-1 receptor signaling pathway is
      known for its antiapoptotic effect, we explored the relationship between gluco
      incretin action, IGF-1 receptor expression and signaling, and apoptosis. RESULTS:
      We found that GLP-1 robustly stimulated IGF-1 receptor expression and Akt
      phosphorylation and that increased Akt phosphorylation was dependent on IGF-1 but
      not insulin receptor expression. We demonstrated that GLP-1-induced Akt
      phosphorylation required active secretion, indicating the presence of an
      autocrine activation mechanism; we showed that activation of IGF-1 receptor
      signaling was dependent on the secretion of IGF-2. We demonstrated, both in MIN6
      cell line and primary beta-cells, that reducing IGF-1 receptor or IGF-2
      expression or neutralizing secreted IGF-2 suppressed GLP-1-induced protection
      against apoptosis. CONCLUSIONS: An IGF-2/IGF-1 receptor autocrine loop operates
      in beta-cells. GLP-1 increases its activity by augmenting IGF-1 receptor
      expression and by stimulating secretion; this mechanism is required for GLP-1
      induced protection against apoptosis. These findings may lead to novel ways of
      preventing beta-cell loss in the pathogenesis of diabetes.

PMID- 19401426
TI  - Allelic depletion of grem1 attenuates diabetic kidney disease.
AB  - OBJECTIVE: Gremlin (grem1) is an antagonist of the bone morphogenetic protein
      family that plays a key role in limb bud development and kidney formation. There
      is a growing appreciation that altered grem1 expression may regulate the
      homeostatic constraints on damage responses in diseases such as diabetic
      nephropathy. RESEARCH DESIGN AND METHODS: Here we explored whether knockout mice
      heterozygous for grem1 gene deletion (grem1(+/-)) exhibit protection from the
      progression of diabetic kidney disease in a streptozotocin-induced model of type
      1 diabetes. RESULTS: A marked elevation in grem1 expression was detected in the
      kidneys and particularly in kidney tubules of diabetic wild-type mice compared
      with those of littermate controls. In contrast, diabetic grem1(+/-) mice
      displayed a significant attenuation in grem1 expression at 6 months of diabetes
      compared with that in age- and sex-matched wild-type controls. Whereas the onset
      and induction of diabetes were similar between grem1(+/-) and wild-type mice,
      several indicators of diabetes-associated kidney damage such as increased
      glomerular basement membrane thickening and microalbuminuria were attenuated in
      grem1(+/-) mice compared with those in wild-type controls. Markers of renal
      damage such as fibronectin and connective tissue growth factor were elevated in
      diabetic wild-type but not in grem1(+/-) kidneys. Levels of pSmad1/5/8 decreased
      in wild-type but not in grem1(+/-) diabetic kidneys, suggesting that bone
      morphogenetic protein signaling may be maintained in the absence of grem1.
      CONCLUSIONS: These data identify grem1 as a potential modifier of renal injury in
      the context of diabetic kidney disease.

PMID- 19401427
TI  - Additive interaction between the renin-angiotensin system and lipid metabolism
      for cancer in type 2 diabetes.
AB  - OBJECTIVE: Clinical and experimental studies suggest cross-talk between lipid
      metabolism and the renin-angiotensin system (RAS) in atherogenesis. The aim of
      this study was to explore interactions between these two systems in mediating
      cancer risk in type 2 diabetes. RESEARCH DESIGN AND METHODS: A prospective cohort
      of 4,160 Chinese patients with type 2 diabetes, free of cancer at enrollment,
      were analyzed using Cox models. Interaction of RAS inhibitors (angiotensin I
      converting enzyme inhibitors or angiotensin II receptor blockers) and statins was
      estimated using relative excess risk due to interaction (RERI), attributable
      proportion due to interaction (AP), and synergy index (S). RERI > 0, AP > 0, or S
      > 1 indicates additive interaction between the two classes of drugs. Molecular
      mechanisms underlying these interactions were explored using a uninephrectomy
      (UNX) rat model with renal carcinogenesis. RESULTS: During 21,992 person-years of
      follow-up, 190 patients developed cancer. Use of RAS inhibitors and statins in
      isolation or combination during follow-up was associated with reduced risk of
      cancer after adjustment for covariates. The multivariable RERI and AP for the
      additive interaction between these drug classes for cancer were significant (0.53
      [95% CI 0.20-0.87] and 2.65 [0.38-4.91], respectively). In the UNX rat model,
      inhibition of the RAS prevented renal cell carcinoma by normalizing
      hydroxymethylglutaryl-CoA reductase (HMGCR) expression and the insulin-like
      growth factor-1 (IGF-1) signaling pathway. CONCLUSIONS: Combined use of RAS
      inhibitors and statins may act synergistically to reduce cancer risk, possibly
      via HMGCR and IGF-1 signaling pathways in high-risk conditions such as type 2
      diabetes.

PMID- 19401428
TI  - High incidence of metabolically active brown adipose tissue in healthy adult
      humans: effects of cold exposure and adiposity.
AB  - OBJECTIVE: The significant roles of brown adipose tissue (BAT) in the regulation
      of energy expenditure and adiposity are established in small rodents but have
      been controversial in humans. The objective is to examine the prevalence of
      metabolically active BAT in healthy adult humans and to clarify the effects of
      cold exposure and adiposity. RESEARCH DESIGN AND METHODS: In vivo 2-[(18)F]fluoro
      2-deoxyglucose (FDG) uptake into adipose tissue was measured in 56 healthy
      volunteers (31 male and 25 female subjects) aged 23-65 years by positron emission
      tomography (PET) combined with X-ray computed tomography (CT). RESULTS: When
      exposed to cold (19 degrees C) for 2 h, 17 of 32 younger subjects (aged 23-35
      years) and 2 of 24 elderly subjects (aged 38-65 years) showed a substantial FDG
      uptake into adipose tissue of the supraclavicular and paraspinal regions, whereas
      they showed no detectable uptake when kept warm (27 degrees C). Histological
      examinations confirmed the presence of brown adipocytes in these regions. The
      cold-activated FDG uptake was increased in winter compared with summer (P <
      0.001) and was inversely related to BMI (P < 0.001) and total (P < 0.01) and
      visceral (P < 0.001) fat areas estimated from CT image at the umbilical level.
      CONCLUSIONS: Our findings, being against the conventional view, indicate the high
      incidence of metabolically active BAT in adult humans and suggest a role in the
      control of body temperature and adiposity.

PMID- 19401430
TI  - Majority of children with type 1 diabetes produce and deposit anti-tissue
      transglutaminase antibodies in the small intestine.
AB  - OBJECTIVE: Anti-tissue transglutaminase (TG2) antibodies are the serological
      marker of celiac disease. Given the close association between celiac disease and
      type 1 diabetes, we investigated the production and deposition of anti-TG2
      antibodies in the jejunal mucosa of type 1 diabetic children. RESEARCH DESIGN AND
      METHODS: Intestinal biopsies were performed in 33 type 1 diabetic patients with a
      normal mucosal architecture: 14 had high levels (potential celiac disease
      patients) and 19 had normal levels of serum anti-TG2 antibodies. All biopsy
      specimens were investigated for intestinal deposits of IgA anti-TG2 antibodies by
      double immunofluorescence. In addition, an antibody analysis using the phage
      display technique was performed on the intestinal biopsy specimens from seven
      type 1 diabetic patients, of whom four had elevated and three had normal levels
      of serum anti-TG2 antibodies. RESULTS: Immunofluorescence studies showed that 11
      of 14 type 1 diabetic children with elevated levels and 11 of 19 with normal
      serum levels of anti-TG2 antibodies presented with mucosal deposits of such
      autoantibodies. The phage display analysis technique confirmed the intestinal
      production of the anti-TG2 antibodies; however, whereas the serum-positive type 1
      diabetic patients showed a preferential use of the VH5 antibody gene family, in
      the serum-negative patients the anti-TG2 antibodies belonged to the VH1 and VH3
      families, with a preferential use of the latter. CONCLUSIONS: Our findings
      demonstrate that there is intestinal production and deposition of anti-TG2
      antibodies in the jejunal mucosa of the majority of type 1 diabetic patients.
      However, only those with elevated serum levels of anti-TG2 antibodies showed the
      VH usage that is typical of the anti-TG2 antibodies that are produced in patients
      with celiac disease.

PMID- 19401431
TI  - Comment on: Torii et al. (2009) Gene silencing of phogrin unveils its essential
      role in glucose-responsive pancreatic beta-cell growth. Diabetes 58:682-692.

PMID- 19401429
TI  - Pig embryonic pancreatic tissue as a source for transplantation in diabetes:
      transient treatment with anti-LFA1, anti-CD48, and FTY720 enables long-term graft
      maintenance in mice with only mild ongoing immunosuppression.
AB  - OBJECTIVE: Defining an optimal costimulatory blockade-based immune suppression
      protocol enabling engraftment and functional development of E42 pig embryonic
      pancreatic tissue in mice. RESEARCH DESIGN AND METHODS: Considering that anti
      CD40L was found to be thrombotic in humans, we sought to test alternative
      costimulatory blockade agents already in clinical use, including CTLA4-Ig, anti
      LFA1, and anti-CD48. These agents were tested in conjunction with T-cell
      debulking by anti-CD4 and anti-CD8 antibodies or with conventional
      immunosuppressive drugs. Engraftment and functional development of E42 pig
      pancreatic tissue was monitored by immunohistology and by measuring pig insulin
      blood levels. RESULTS: Fetal pig pancreatic tissue harvested at E42, or even as
      early as at E28, was fiercely rejected in C57BL/6 mice and in Lewis rats. A novel
      immune suppression comprising anti-LFA1, anti-CD48, and FTY720 afforded optimal
      growth and functional development. Cessation of treatment with anti-LFA1 and anti
      CD48 at 3 months posttransplant did not lead to graft rejection, and graft
      maintenance could be achieved for >8 months with twice-weekly low-dose FTY720
      treatment. These grafts exhibited normal morphology and were functional, as
      revealed by the high pig insulin blood levels in the transplanted mice and by the
      ability of the recipients to resist alloxan induced diabetes. CONCLUSIONS: This
      novel protocol, comprising agents that simulate those approved for clinical use,
      offer an attractive approach for embryonic xenogeneic transplantation. Further
      studies in nonhuman primates are warranted.

PMID- 19401432
TI  - GPR40: good cop, bad cop?

PMID- 19401433
TI  - Adipose tissue plasticity in catch-up-growth trajectories to metabolic syndrome:
      hyperplastic versus hypertrophic catch-up fat.

PMID- 19401434
TI  - Overexpression of GPR40 in pancreatic beta-cells augments glucose-stimulated
      insulin secretion and improves glucose tolerance in normal and diabetic mice.
AB  - OBJECTIVE: GPR40 is a G protein-coupled receptor regulating free fatty acid
      induced insulin secretion. We generated transgenic mice overexpressing the hGPR40
      gene under control of the mouse insulin II promoter and used them to examine the
      role of GPR40 in the regulation of insulin secretion and glucose homeostasis.
      RESEARCH DESIGN AND METHODS: Normal (C57BL/6J) and diabetic (KK) mice
      overexpressing the hGPR40 gene under control of the insulin II promoter were
      generated, and their glucose metabolism and islet function were analyzed.
      RESULTS: In comparison with nontransgenic littermates, hGPR40 transgenic mice
      exhibited improved oral glucose tolerance with an increase in insulin secretion.
      Although islet morphologic analysis showed no obvious differences between hGPR40
      transgenic and nontransgenic mice, isolated islets from hGPR40 transgenic mice
      had enhanced insulin secretion in response to high glucose (16 mmol/l) compared
      with those from nontransgenic mice, and they both had similar low glucose (3
      mmol/l)-stimulated insulin secretion. In addition, hGPR40 transgenic islets
      significantly increased insulin secretion against a naturally occurring agonist
      palmitate in the presence of 11 mmol/l glucose. hGPR40 transgenic mice were also
      found to be resistant to high-fat diet-induced glucose intolerance, and hGPR40
      transgenic mice harboring KK background showed augmented insulin secretion and
      improved oral glucose tolerance compared with nontransgenic littermates.
      CONCLUSIONS: Our results suggest that GPR40 may have a role in regulating glucose
      stimulated insulin secretion and plasma glucose levels in vivo and that
      pharmacological activation of GPR40 may provide a novel insulin secretagogue
      beneficial for the treatment of type 2 diabetes.

PMID- 19401435
TI  - UniPrime2: a web service providing easier Universal Primer design.
AB  - The UniPrime2 web server is a publicly available online resource which
      automatically designs large sets of universal primers when given a gene reference
      ID or Fasta sequence input by a user. UniPrime2 works by automatically retrieving
      and aligning homologous sequences from GenBank, identifying regions of
      conservation within the alignment, and generating suitable primers that can be
      used to amplify variable genomic regions. In essence, UniPrime2 is a suite of
      publicly available software packages (Blastn, T-Coffee, GramAlign, Primer3),
      which reduces the laborious process of primer design, by integrating these
      programs into a single software pipeline. Hence, UniPrime2 differs from previous
      primer design web services in that all steps are automated, linked, saved and
      phylogenetically delimited, only requiring a single user-defined gene reference
      ID or input sequence. We provide an overview of the web service and wet
      laboratory validation of the primers generated. The system is freely accessible
      at: http://uniprime.batlab.eu. UniPrime2 is licenced under a Creative Commons
      Attribution Noncommercial-Share Alike 3.0 Licence.

PMID- 19401436
TI  - Cellular responses to DNA double-strand breaks after low-dose gamma-irradiation.
AB  - DNA double-strand breaks (DSBs) are a serious threat to genome stability and cell
      viability. Although biological effects of low levels of radiation are not clear,
      the risks of low-dose radiation are of societal importance. Here, we directly
      monitored induction and repair of single DSBs and quantitatively analyzed the
      dynamics of interaction of DNA repair proteins at individual DSB sites in living
      cells using 53BP1 fused to yellow fluorescent protein (YFP-53BP1) as a surrogate
      marker. The number of DSBs formed was linear with dose from 5 mGy to 1 Gy. The
      DSBs induced by very low radiation doses (5 mGy) were repaired with efficiency
      similar to repair of DSBs induced at higher doses. The YFP-53BP1 foci are dynamic
      structures: 53BP1 rapidly and reversibly interacted at these DSB sites. The time
      frame of recruitment and affinity of 53BP1 for DSB sites were indistinguishable
      between low and high doses, providing mechanistic evidence for the similar DSB
      repair after low- and high-dose radiation. These findings have important
      implications for estimating the risk associated with low-dose radiation exposure
      on human health.

PMID- 19401438
TI  - S-adenosyl homocysteine and DNA ends stimulate promiscuous nuclease activities in
      the Type III restriction endonuclease EcoPI.
AB  - In the absence of the methyl donor S-adenosyl methionine and under certain
      permissive reaction conditions, EcoPI shows non-specific endonuclease activity.
      We show here that the cofactor analogue S-adenosyl homocysteine promotes this
      promiscuous DNA cleavage. Additionally, an extensive exonuclease-like processing
      of the DNA is also observed that can even result in digestion of non-specific DNA
      in trans. We suggest a model for how DNA communication events initiating from non
      specific sites, and in particular free DNA ends, could produce the observed
      cleavage patterns.

PMID- 19401437
TI  - FMM: a web server for metabolic pathway reconstruction and comparative analysis.
AB  - Synthetic Biology, a multidisciplinary field, is growing rapidly. Improving the
      understanding of biological systems through mimicry and producing bio-orthogonal
      systems with new functions are two complementary pursuits in this field. A web
      server called FMM (From Metabolite to Metabolite) was developed for this purpose.
      FMM can reconstruct metabolic pathways form one metabolite to another metabolite
      among different species, based mainly on the Kyoto Encyclopedia of Genes and
      Genomes (KEGG) database and other integrated biological databases. Novel
      presentation for connecting different KEGG maps is newly provided. Both local and
      global graphical views of the metabolic pathways are designed. FMM has many
      applications in Synthetic Biology and Metabolic Engineering. For example, the
      reconstruction of metabolic pathways to produce valuable metabolites or secondary
      metabolites in bacteria or yeast is a promising strategy for drug production. FMM
      provides a highly effective way to elucidate the genes from which species should
      be cloned into those microorganisms based on FMM pathway comparative analysis.
      Consequently, FMM is an effective tool for applications in synthetic biology to
      produce both drugs and biofuels. This novel and innovative resource is now freely
      available at http://FMM.mbc.nctu.edu.tw/.

PMID- 19401439
TI  - Highly efficient incorporation of the fluorescent nucleotide analogs tC and tCO
      by Klenow fragment.
AB  - Studies of the mechanisms by which DNA polymerases select the correct nucleotide
      frequently employ fluorescently labeled DNA to monitor conformational
      rearrangements of the polymerase-DNA complex in response to incoming nucleotides.
      For this purpose, fluorescent base analogs play an increasingly important role
      because they interfere less with the DNA-protein interaction than do tethered
      fluorophores. Here we report the incorporation of the 5'-triphosphates of two
      exceptionally bright cytosine analogs, 1,3-diaza-2-oxo-phenothiazine (tC) and its
      oxo-homolog, 1,3-diaza-2-oxo-phenoxazine (tC(O)), into DNA by the Klenow
      fragment. Both nucleotide analogs are polymerized with slightly higher efficiency
      opposite guanine than cytosine triphosphate and are shown to bind with nanomolar
      affinity to the DNA polymerase active site, according to fluorescence anisotropy
      measurements. Using this method, we perform competitive binding experiments and
      show that they can be used to determine the dissociation constant of any given
      natural or unnatural nucleotide. The results demonstrate that the active site of
      the Klenow fragment is flexible enough to tolerate base pairs that are size
      expanded in the major groove. In addition, the possibility to enzymatically
      polymerize a fluorescent nucleotide with high efficiency complements the tool box
      of biophysical probes available to study DNA replication.

PMID- 19401440
TI  - Remodeling of chromatin structure within the promoter is important for bmp-2
      induced fgfr3 expression.
AB  - Fibroblast growth factor receptor 3 (FGFR3) plays an important role in cartilage
      development. Although upregulation of FGFR3 expression in response to bone
      morphogenetic protein-2 (BMP-2) has been reported, the molecular mechanisms
      remain unknown. In this study, we used in vivo approaches to characterize BMP-2
      induced alterations in the chromatin organization of the FGFR3 core promoter.
      Chromatin immunoprecipitation analysis demonstrated that the binding of Brg1, a
      component of the SWI/SNF remodeling complex, may selectively remodel a chromatin
      region (encompassing nucleotide -90 to +35), uncovering the transcription start
      site and three Sp1-binding sites, as revealed by nuclease digestion
      hypersensitivity assays. We then showed an increase in the association of Sp1
      with the proximal promoter, followed by the recruitment of p300, resulting in a
      change of the histone 'code', such as in phosphorylation and methylation.
      Collectively, our study results suggest a model for BMP-2-induced FGFR3
      expression in which the core promoter architecture is specifically regulated.

PMID- 19401442
TI  - Type 2 diabetes prevention in the real world: three-year results of the GOAL
      lifestyle implementation trial.
AB  - OBJECTIVE We study the effectiveness of the GOAL Lifestyle Implementation Trial
      at the 36-month follow-up. RESEARCH DESIGN AND METHODS Participants (n = 352,
      type 2 diabetes risk score FINDRISC = 16.2 +/- 3.3, BMI 32.6 +/- 5.0 kg/m(2))
      received six lifestyle counseling sessions over 8 months. Measurements were at
      baseline, 12 months (88.6%), and 36 months (77.0%). RESULTS Statistically
      significant risk reduction at 12 months was maintained at 36 months in weight (
      1.0 +/- 5.6 kg), BMI (-0.5 +/- 2.1 kg/m(2)), and serum total cholesterol (-0.4 +/
      1.1 mmol/l). CONCLUSIONS Maintenance of risk reduction in this "real world"
      trial proves the intervention's potential for significant public health impact.

PMID- 19401441
TI  - Identification of Apurinic/apyrimidinic endonuclease 1 (APE1) as the
      endoribonuclease that cleaves c-myc mRNA.
AB  - Endonucleolytic cleavage of the coding region determinant (CRD) of c-myc mRNA
      appears to play a critical role in regulating c-myc mRNA turnover. Using (32)P
      labeled c-myc CRD RNA as substrate, we have purified and identified two
      endoribonucleases from rat liver polysomes that are capable of cleaving the
      transcript in vitro. A 17-kDa enzyme was identified as RNase1.
      Apurinic/apyrimidinic (AP) DNA endonuclease 1 (APE1) was identified as the 35-kDa
      endoribonuclease that preferentially cleaves in between UA and CA dinucleotides
      of c-myc CRD RNA. APE1 was further confirmed to be the 35-kDa endoribonuclease
      because: (i) the endoribonuclease activity of the purified 35-kDa native enzyme
      was specifically immuno-depleted with APE1 monoclonal antibody, and (ii)
      recombinant human APE1 generated identical RNA cleavage patterns as the native
      liver enzyme. Studies using E96A and H309N mutants of APE1 suggest that the
      endoribonuclease activity for c-myc CRD RNA shares the same active center with
      the AP-DNA endonuclease activity. Transient knockdown of APE1 in HeLa cells led
      to increased steady-state level of c-myc mRNA and its half-life. We conclude that
      the ability to cleave RNA dinucleotides is a previously unidentified function of
      APE1 and it can regulate c-myc mRNA level possibly via its endoribonuclease
      activity.

PMID- 19401444
TI  - Body iron stores and glucose intolerance in premenopausal women: role of
      hyperandrogenism, insulin resistance, and genomic variants related to
      inflammation, oxidative stress, and iron metabolism.
AB  - OBJECTIVE Increased serum ferritin levels and iron stores may be involved in the
      development of abnormal glucose tolerance in women presenting with obesity and/or
      polycystic ovary syndrome (PCOS). We aimed to study the determinants of serum
      ferritin levels in premenopausal women among indexes of insulin resistance,
      adiposity, hyperandrogenism, and genotypes pertaining to inflammation, oxidative
      stress, and iron metabolism. RESEARCH DESIGN AND METHODS A total of 257
      premenopausal women, classified depending on the presence or absence of PCOS,
      obesity, and/or abnormal glucose tolerance, underwent a complete metabolic
      evaluation, serum ferritin, haptoglobin, and C-reactive protein (CRP)
      measurements, and genotyping for proinflammatory and prooxidant variants and
      mutations in the HFE gene. RESULTS Serum ferritin concentrations were increased
      in women presenting with PCOS and/or abnormal glucose tolerance, independent of
      obesity. A stepwise multivariate linear regression analysis (R(2) = 0.18, P <
      0.0001) retained menstrual dysfunction (beta = 0.14, P = 0.035), free
      testosterone (beta = 0.14, P = 0.052), insulin sensitivity index (beta = -0.12, P
      = 0.012), the His63Asp variant in HFE (beta = 0.16, P = 0.008), and abnormal
      glucose tolerance (beta = 0.15, P = 0.015) as significant predictors of the
      logarithm of ferritin levels, whereas CRP, haptoglobin, waist-to-hip ratio, or
      variants in the TNFalpha, TNFRSF1B, IL6, IL6ST, IL6Ralpha, PON1, and HFE
      Cys282Tyr mutation exerted no influence. CONCLUSIONS Androgen excess (partly
      because of hyperandrogenemia and partly because of menstrual dysfunction),
      insulin resistance, abnormal glucose tolerance, and the HFE His63Asp variant
      correlate with ferritin levels in premenopausal women.

PMID- 19401443
TI  - Diabetes numeracy: an overlooked factor in understanding racial disparities in
      glycemic control.
AB  - OBJECTIVE: Understanding the reasons and eliminating the pervasive health
      disparities in diabetes is a major research, clinical, and health policy goal. We
      examined whether health literacy, general numeracy, and diabetes-related numeracy
      explain the association between African American race and poor glycemic control
      (A1C) in patients with diabetes. RESEARCH DESIGN AND METHODS: Adults with type 2
      diabetes (n = 383) were enrolled in a cross-sectional study at primary care and
      diabetes clinics at three medical centers. Data collected included the following:
      self-reported race, health literacy, general numeracy, diabetes-related numeracy,
      A1C, and sociodemographic factors. A series of structural equation models were
      estimated to explore the interrelations between variables and test for mediation.
      RESULTS: In model 1, younger age (r = -0.21, P < 0.001), insulin use (r = 0.27, P
      < 0.001), greater years with diabetes (r = 0.16, P < 0.01), and African American
      race (r = 0.12, P < 0.01) were all associated with poorer glycemic control. In
      model 2, diabetes-related numeracy emerged as a strong predictor of A1C (r = 
      0.46, P < 0.001), reducing the association between African American and poor
      glycemic control to nonsignificance (r = 0.10, NS). In model 3, African American
      race and older age were associated with lower diabetes-related numeracy; younger
      age, insulin use, more years with diabetes, and lower diabetes-related numeracy
      were associated with poor glycemic control. CONCLUSIONS: Diabetes-related
      numeracy reduced the explanatory power of African American race, such that low
      diabetes-related numeracy, not African American race, was significantly related
      to poor glycemic control. Interventions that address numeracy could help to
      reduce racial disparities in diabetes.

PMID- 19401445
TI  - GHb level and subsequent mortality among adults in the U.S.
AB  - OBJECTIVE To examine the association of hyperglycemia, as measured by GHb, with
      subsequent mortality in a nationally representative sample of adults. RESEARCH
      DESIGN AND METHODS We included adults aged > or =20 years who participated in
      Third National Health and Nutrition Examination Survey (1988-1994) and had
      complete information, including baseline diabetes status by self-report and
      measured GHb (n = 19,025) and follow-up through the end of 2000 for mortality.
      RESULTS In the overall population, higher levels of GHb were associated with
      increased risk of mortality from all causes, heart disease, and cancer. After
      adjustment for potential risk factors, the relative hazard (RH) for adults with
      GHb > or =8% compared with adults with GHb <6% was 2.59 (95% CI 1.88-3.56) for
      all-cause mortality, 3.38 (1.98-5.77) for heart disease mortality, and 2.64 (1.17
      5.97) for cancer mortality. Among adults with diagnosed diabetes, having GHb > or
      =8% compared with GHb <6% was associated with higher all-cause mortality (RH
      1.68, 95% CI 1.03-2.74) and heart disease mortality (2.48, 1.09-5.64), but there
      was no increased risk of cancer mortality by GHb category. Among adults without
      diagnosed diabetes, there was no significant association of all-cause, heart
      disease, or cancer mortality and GHb category. CONCLUSIONS These results
      highlight the importance of GHb levels in mortality risk among a nationally
      representative sample of adults with and without diagnosed diabetes and indicate
      that higher levels are associated with increased mortality in adults with
      diabetes.

PMID- 19401446
TI  - Physical inactivity and obesity underlie the insulin resistance of aging.
AB  - OBJECTIVE Age-associated insulin resistance may underlie the higher prevalence of
      type 2 diabetes in older adults. We examined a corollary hypothesis that obesity
      and level of chronic physical inactivity are the true causes for this ostensible
      effect of aging on insulin resistance. RESEARCH DESIGN AND METHODS We compared
      insulin sensitivity in 7 younger endurance-trained athletes, 12 older athletes,
      11 younger normal-weight subjects, 10 older normal-weight subjects, 15 younger
      obese subjects, and 15 older obese subjects using a glucose clamp. The
      nonathletes were sedentary. RESULTS Insulin sensitivity was not different in
      younger endurance-trained athletes versus older athletes, in younger normal
      weight subjects versus older normal-weight subjects, or in younger obese subjects
      versus older obese subjects. Regardless of age, athletes were more insulin
      sensitive than normal-weight sedentary subjects, who in turn were more insulin
      sensitive than obese subjects. CONCLUSIONS Insulin resistance may not be
      characteristic of aging but rather associated with obesity and physical
      inactivity.

PMID- 19401447
TI  - Enhancing the antitumor activity of adriamycin and ionizing radiation.
AB  - Overexpression of manganese superoxide dismutase (MnSOD), when combined with
      certain chemicals that inhibit peroxide removal, increases cancer cell
      cytotoxicity. Elevating MnSOD levels in cells enhances the conversion of
      superoxide (O(2)(*-)) to hydrogen peroxide (H(2)O(2)), combined with inhibiting
      the removal of H(2)O(2), further increases H(2)O(2) levels, leading to increased
      cytotoxicity. We hypothesized that increasing endogenous O(2)(*-) production in
      cells that were pretreated with adenoviral MnSOD (AdMnSOD) plus 1,3-bis(2
      chloroethyl)-1-nitrosourea (BCNU) would lead to an increased level of
      intracellular H(2)O(2) accumulation and increased cell killing. The cytotoxic
      effects of Adriamycin or radiation, agents known to produce O(2)(*-), were
      determined in MDA-MB-231 breast cancer cells pretreated with AdMnSOD plus BCNU
      both in vitro and in vivo. In vitro, AdMnSOD plus BCNU sensitized cells to the
      cytotoxicity of Adriamycin or radiation. In vivo, AdMnSOD, BCNU, and Adriamycin
      or ionizing radiation inhibited tumor growth and prolonged survival. The results
      suggest that agents that produce O(2)(*-) in combination with AdMnSOD plus BCNU
      may represent a powerful new antitumor regimen against breast cancer.

PMID- 19401449
TI  - PI3K pathway activation mediates resistance to MEK inhibitors in KRAS mutant
      cancers.
AB  - The RAS pathway is one of the most frequently deregulated pathways in cancer. RAS
      signals through multiple effector pathways, including the RAF/mitogen-activated
      protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase
      (MEK)/ERK MAPK and phosphatidylinositol 3-kinase (PI3K)-AKT signaling cascades.
      The oncogenic potential of these effector pathways is illustrated by the frequent
      occurrence of activating mutations in BRAF and PIK3CA as well as loss-of-function
      mutations in the tumor suppressor PTEN, a negative regulator of PI3K. Previous
      studies have found that whereas BRAF mutant cancers are highly sensitive to MEK
      inhibition, RAS mutant cancers exhibit a more variable response. The molecular
      mechanisms responsible for this heterogeneous response remain unclear. In this
      study, we show that PI3K pathway activation strongly influences the sensitivity
      of RAS mutant cells to MEK inhibitors. Activating mutations in PIK3CA reduce the
      sensitivity to MEK inhibition, whereas PTEN mutations seem to cause complete
      resistance. We further show that down-regulation of PIK3CA resensitizes cells
      with co-occurring KRAS and PIK3CA mutations to MEK inhibition. At the molecular
      level, the dual inhibition of both pathways seems to be required for complete
      inhibition of the downstream mammalian target of rapamycin effector pathway and
      results in the induction of cell death. Finally, we show that whereas
      inactivation of either the MEK or PI3K pathway leads to partial tumor growth
      inhibition, targeted inhibition of both pathways is required to achieve tumor
      stasis. Our study provides molecular insights that help explain the heterogeneous
      response of KRAS mutant cancers to MEK pathway inhibition and presents a strong
      rationale for the clinical testing of combination MEK and PI3K targeted
      therapies.

PMID- 19401448
TI  - Heregulin regulates prolactinoma gene expression.
AB  - To investigate the role of p185(her2/neu)/ErbB3 signaling in pituitary tumor
      function, we examined these receptors in human prolactinomas. Immunofluorescent
      p185(her2/neu) was detected in almost all (seven of eight), and ErbB3 expression
      in a subset (four of eight) of tumors (seven adenomas and one carcinoma).
      Quantitative PCR also showed abundant ErbB3 mRNA in tumor specimens derived from
      a rarely encountered prolactin-cell carcinoma. Activation of p185(c-neu)/ErbB3
      signaling with heregulin, the ErbB3 ligand, in rat lacto-somatotroph (GH4C1)
      tumor cells specifically induced prolactin (PRL) mRNA expression approximately 5
      fold and PRL secretion approximately 4-fold, whereas growth hormone expression
      was unchanged. Heregulin (6 nmol/L) induced tyrosine phosphorylation and ErbB3
      and p185(c-neu) heterodimerization, with subsequent activation of intracellular
      ERK and Akt. The Akt signal was specific to ErbB3 activation by heregulin, and
      was not observed in response to epidermal growth factor activation of epidermal
      growth factor receptor. Gefitinib, the tyrosine kinase inhibitor, suppressed
      heregulin-mediated p185(c-neu)/ErbB3 signaling to PRL. Heregulin induction of PRL
      was also abrogated by transfecting cells with short interfering RNA directed
      against ErbB3. Pharmacologic inhibition of heregulin-induced phosphoinositide-3
      kinase/Akt (with LY294002) and ERK (with U0126) signaling, as well as short
      interfering RNA-mediated mitogen-activated protein kinase-1 down-regulation,
      showed ERK signaling as the primary transducer of heregulin signaling to PRL.
      These results show ErbB3 expression in human prolactinomas and a novel ErbB3
      mediated mechanism for PRL regulation in experimental lactotroph tumors. Targeted
      inhibition of up-regulated p185(c-neu)/ErbB3 activity could be useful for the
      treatment of aggressive prolactinomas resistant to conventional therapy.

PMID- 19401450
TI  - Identification of PDE4D as a proliferation promoting factor in prostate cancer
      using a Sleeping Beauty transposon-based somatic mutagenesis screen.
AB  - Retroviral and transposon-based mutagenesis screens in mice have been useful for
      identifying candidate cancer genes for some tumor types. However, many of the
      organs that exhibit the highest cancer rates in humans, including the prostate,
      have not previously been amenable to these approaches. This study shows for the
      first time that the Sleeping Beauty transposon system can be used to identify
      candidate prostate cancer genes in mice. Somatic mobilization of a mutagenic
      transposon resulted in focal epithelial proliferation and hyperplasia in the
      prostate. Efficient methods were established to identify transposon insertion
      sites in these lesions, and analysis of transposon insertions identified
      candidate prostate cancer genes at common insertion sites, including Pde4d. PDE4D
      was also overexpressed in human prostate cancer patient samples and cell lines,
      and changes in PDE4D mRNA isoform expression were observed in human prostate
      cancers. Furthermore, knockdown of PDE4D reduced the growth and migration of
      prostate cancer cells in vitro, and knockdown of PDE4D reduced the growth and
      proliferation rate of prostate cancer xenografts in vivo. These data indicate
      that PDE4D functions as a proliferation promoting factor in prostate cancer, and
      the Sleeping Beauty transposon system is a useful tool for identifying candidate
      prostate cancer genes.

PMID- 19401452
TI  - Disruption of the E2 gene is a common and early event in the natural history of
      cervical human papillomavirus infection: a longitudinal cohort study.
AB  - Integration of high-risk human papillomavirus (HPV) types into the host-cell
      genome disrupts the HPV regulatory E2 protein, resulting in a loss of negative
      feedback control of viral oncogene expression; this disruption has been
      considered a critical event in the pathogenesis of cervical neoplasia, and a
      potential biomarker of progressive disease. However, using serial samples taken
      from a cohort of young women who were recruited soon after they first had sexual
      intercourse, we show that disruption of the E2 gene is a common and early event
      in the natural history of incident cervical HPV infections. The E2 gene was
      significantly more likely to be disrupted in women who tested positive for HPV18
      in their baseline sample than in those who tested positive for HPV16 [26% versus
      58%; relative risk, 2.26; 95% confidence interval (CI), 1.38-3.71; chi(2), 9.23;
      1 degree of freedom (df); P = 0.002]. Among women with an intact E2 gene in their
      baseline sample, the median time to first detection of E2 disruption was also
      shorter for those who tested positive for HPV18 than HPV16 (5.7 versus 10.9
      months; hazards ratio, 1.93; 95% CI, 0.84-4.44; chi(2), 2.49; 1 df; P = 0.11).
      This tendency for HPV18 to integrate early, coupled with the substantial
      reduction in viral load in HPV18-positive samples in which E2 is disrupted, may
      explain why HPV18-associated disease is often reported to be characterized by
      minor cytologic changes, which underestimate the severity of the underlying
      histologic abnormality.

PMID- 19401453
TI  - Regulation of secondary antigen-specific CD8(+) T-cell responses by natural
      killer T cells.
AB  - The physiologic function of natural killer T (NKT) cells in adaptive immunity
      remains largely unknown because most studies have used NKT cell agonists. In the
      present study, the role of NKT cells during the secondary effector phase was
      investigated separately from the primary immunization phase via adoptive transfer
      of differentiated effector T cells into naive recipients. We found that secondary
      antitumor CD8(+) T-cell responses were optimal when NKT cells were present. Tumor
      specific CD8(+) effector T cells responded less strongly to tumor cell challenge
      in NKT cell-deficient recipients than in recipients with intact NKT cells. NKT
      cell-mediated enhancement of the secondary antitumor CD8(+) T-cell response was
      concurrent with increased number and activity of tumor-specific CD8(+) T cells.
      These findings provide the first demonstration of a direct role for NKT cells in
      the regulation of antigen-specific secondary T-cell responses without the use of
      exogenous NKT cell agonists such as alpha-galactosylceramide (alpha-GalCer).
      Furthermore, forced activation of NKT cells with alpha-GalCer during the
      secondary immune response in suboptimally immunized animals enhanced otherwise
      poor tumor rejection responses. Taken together, our findings strongly emphasize
      the importance of NKT cells in secondary CD8(+) T-cell immune responses.

PMID- 19401451
TI  - Cellular source and amount of vascular endothelial growth factor and platelet
      derived growth factor in tumors determine response to angiogenesis inhibitors.
AB  - Vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF),
      and their receptors are important targets in cancer therapy based on angiogenesis
      inhibition. However, it is unclear whether inhibition of VEGF and PDGF together
      is more effective than inhibition of either one alone. Here, we used two
      contrasting tumor models to compare the effects of inhibiting VEGF or PDGF alone,
      by adenovirally generated soluble receptors, to the effects of inhibiting both
      together. In RIP-Tag2 tumors, VEGF and PDGF inhibition together reduced tumor
      vascularity and abundance of pericytes. However, VEGF inhibition reduced tumor
      vascularity without decreasing pericyte density, and PDGF inhibition reduced
      pericytes without reducing tumor vascularity. By contrast, in Lewis lung
      carcinomas (LLC), inhibition of VEGF or PDGF reduced blood vessels and pericytes
      to the same extent as did inhibition of both together. Similar results were
      obtained using tyrosine kinase inhibitors AG-013736 and imatinib. In LLC, VEGF
      expression was largely restricted to pericytes and PDGF was largely restricted to
      endothelial cells, but, in RIP-Tag2 tumors, expression of both growth factors was
      more widespread and significantly greater than in LLC. These findings suggest
      that inhibition of PDGF in LLC reduced pericytes, and then tumor vessels
      regressed because pericytes were the main source of VEGF. The vasculature of RIP
      Tag2 tumors, in which most VEGF is from tumor cells, was more resistant to PDGF
      inhibition. The findings emphasize the interdependence of pericytes and
      endothelial cells in tumors and the importance of tumor phenotype in determining
      the cellular effects of VEGF and PDGF inhibitors on tumor vessels.

PMID- 19401454
TI  - Involvement of NADPH oxidase in oxidized LDL-induced upregulation of heat shock
      factor-1 and plasminogen activator inhibitor-1 in vascular endothelial cells.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is implicated in thrombogenesis,
      inflammation, and extracellular matrix remodeling. Previous studies indicated
      that oxidized low-density lipoprotein (LDL) stimulated the generation of PAI-1 in
      vascular endothelial cells (EC). The present study demonstrated that LDL oxidized
      by copper, iron, or 3-morpholinosydnonimine increased the expression of NADPH
      oxidase (NOX) 2, PAI-1, and heat shock factor-1 (HSF1) in human umbilical vein EC
      or coronary artery EC compared with LDL or vehicle. Diphenyleneiodonium, a NOX
      inhibitor, prevented the increases of the expression of HSF1 and PAI-1 in EC
      induced by oxidized LDLs. Small-interference RNA (siRNA) for p22(phox), an
      essential subunit of NOX, prevented oxidized LDL-induced expression of NOX2,
      HSF1, and PAI-1 in EC. HSF1 siRNA inhibited oxidized LDL-induced expression of
      PAI-1 and HSF1, but not NOX2, in EC. The binding of HSF1 to PAI-1 promoter and
      the activity of PAI-1 promoter in EC were enhanced by oxidized LDL. Butylated
      hydroxytulene, a potent antioxidant, inhibited oxidized LDL-induced release of
      hydrogen peroxide (H(2)O(2)) and the expression of NOX2, HSF1, and PAI-1 in EC.
      Treatment with H(2)O(2) increased the abundance of NOX2, HSF1, and PAI-1 in EC.
      The results of the present study indicate that oxidized LDL-induced expression of
      NOX may lead to the elevated release of reactive oxygen species, the activation
      of HSF1, and the enhancement of the transcription of PAI-1 gene in cultured
      vascular EC.

PMID- 19401456
TI  - Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells.
AB  - Ghrelin is a peptide hormone with many known functions, including orexigenic,
      blood glucose-regulatory, and antidepressant actions, among others. Mature
      ghrelin is unique in that it is the only known naturally occurring peptide to be
      posttranslationally modified by O-acylation with octanoate. This acylation is
      required for many of ghrelin's actions, including its effects on promoting
      increases in food intake and body weight. GOAT (ghrelin O-acyltransferase), one
      of 16 members of the MBOAT family of membrane-bound O-acyltransferases, has
      recently been identified as the enzyme responsible for catalyzing the addition of
      the octanoyl group to ghrelin. Although the initial reports of GOAT have
      localized its encoding mRNA to tissues known to contain ghrelin, it is as yet
      unclear whether the octanoylation occurs within ghrelin-producing cells or in
      neighboring cells. Here, we have performed dual-label histochemical analysis on
      mouse stomach sections and quantitative PCR on mRNAs from highly enriched pools
      of mouse gastric ghrelin cells to demonstrate a high degree of GOAT mRNA
      expression within ghrelin-producing cells of the gastric oxyntic mucosa. We also
      demonstrate that GOAT is the only member of the MBOAT family whose expression is
      highly enriched within gastric ghrelin cells and whose whole body distribution
      mirrors that of ghrelin.

PMID- 19401455
TI  - Leucine restriction inhibits chondrocyte proliferation and differentiation
      through mechanisms both dependent and independent of mTOR signaling.
AB  - Linear growth in children is sensitive to nutritional status. Amino acids, in
      particular leucine, have been shown to regulate cell growth, proliferation, and
      differentiation through the mammalian target of rapamycin (mTOR), a nutrient
      sensing protein kinase. Having recently demonstrated a role for mTOR in
      chondrogenesis, we hypothesized that leucine restriction, acting through mTOR,
      would inhibit growth plate chondrocyte proliferation and differentiation. The
      effect of leucine restriction was compared with that of the specific mTOR
      inhibitor, rapamycin. Leucine restriction produced a dose-dependent inhibition of
      fetal rat metatarsal explant growth. This was accounted by reduced cell
      proliferation and hypertrophy but not apoptosis. mTOR activity, as reflected by
      ribosomal protein S6 phosphorylation, was only partially inhibited by leucine
      restriction, whereas rapamycin abolished S6 phosphorylation. In chondrogenic
      ATDC5 cells, leucine restriction inhibited cell number, proteoglycan
      accumulation, and collagen X expression despite minimal inhibition of mTOR.
      Microarray analysis demonstrated that the effect of leucine restriction on ATDC5
      cell gene expression differed from that of rapamycin. Out of 1,571 genes affected
      by leucine restriction and 535 genes affected by rapamycin, only 176 genes were
      affected by both. These findings indicate that the decreased chondrocyte growth
      and differentiation associated with leucine restriction is only partly
      attributable to inhibition of mTOR signaling. Thus nutrient restriction appears
      to directly modulate bone growth through unidentified mTOR-independent mechanisms
      in addition to the well-characterized mTOR nutrient-sensing pathway.

PMID- 19401457
TI  - Neutral lipid storage disease: genetic disorders caused by mutations in adipose
      triglyceride lipase/PNPLA2 or CGI-58/ABHD5.
AB  - Neutral lipid storage disease (NLSD) is a group of autosomal recessive disorders
      characterized by the excessive accumulation of neutral lipids in multiple
      tissues. Recently, two genes, adipose triglyceride lipase (ATGL/PNPLA2) and
      comparative gene identification-58 (CGI-58/ABHD5), have been shown to cause NLSD.
      ATGL specifically hydrolyzes the first fatty acid from triacylglycerols (TG) and
      CGI-58/ABHD5 stimulates ATGL activity by a currently unknown mechanism. Mutations
      in both the ATGL and the CGI-58 genes are associated with systemic TG
      accumulation, yet the resulting clinical manifestations are not identical.
      Patients with defective ATGL function suffer from more severe myopathy (NLSDM)
      than patients with defective CGI-58 function. On the other hand, CGI-58 mutations
      are always associated with ichthyosis (NLSDI), which was not observed in patients
      with defective ATGL function. These observations indicate an ATGL-independent
      function of CGI-58. This review summarizes recent findings with the goal of
      relating structural variants of ATGL and CGI-58 to functional consequences in
      lipid metabolism.

PMID- 19401458
TI  - Dynamics of glutathione and ophthalmate traced with 2H-enriched body water in
      rats and humans.
AB  - We developed a LC-MS-MS assay of the (2)H labeling of free glutathione (GSH) and
      bound glutathione [GSSR; which includes all DTT-reducible forms, primarily
      glutathione disulfide (GSSG) and mixed disulfides with proteins] and ophthalmate
      (an index of GSH depletion) labeled from (2)H-enriched body water. In rats whose
      body water was 2.5% (2)H enriched for up to 31 days, GSH labeling follows a
      complex pattern because of different rates of labeling of its constitutive amino
      acids. In rats infused with [(13)C(2),(15)N-glycine]glutathione, the rate of
      appearance of plasma GSH was 2.1 micromol.min(-1).kg(-1), and the half-life of
      plasma GSH/GSSR was 6-8 min. In healthy humans whose body fluids were 0.5% (2)H
      enriched, the (2)H labeling of GSH/GSSR and ophthalmate can be precisely measured
      after 4 h, with GSH being more rapidly labeled than GSSR. Since plasma GSH/GSSR
      derives mostly from liver, this technique opens the way to 2) probe noninvasively
      the labeling pattern and redox status of the liver GSH system in humans and 2)
      assess the usefulness of ophthalmate as an index of GSH depletion.

PMID- 19401459
TI  - PGC-1alpha mediates exercise-induced skeletal muscle VEGF expression in mice.
AB  - The aim of the present study was to test the hypothesis that PGC-1alpha is
      required for exercise-induced VEGF expression in both young and old mice and that
      AMPK activation leads to increased VEGF expression through a PGC-1alpha-dependent
      mechanism. Whole body PGC-1alpha knockout (KO) and littermate wild-type (WT) mice
      were submitted to either 1) 5 wk of exercise training, 2) lifelong (from 2 to 13
      mo of age) exercise training in activity wheel, 3) a single exercise bout, or 4)
      4 wk of daily subcutaneous AICAR or saline injections. In skeletal muscle of PGC
      1alpha KO mice, VEGF protein expression was approximately 60-80% lower and the
      capillary-to-fiber ratio approximately 20% lower than in WT. Basal VEGF mRNA
      expression was similar in WT and PGC-1alpha KO mice, but acute exercise and AICAR
      treatment increased the VEGF mRNA content in WT mice only. Exercise training of
      young mice increased skeletal muscle VEGF protein expression approximately 50% in
      WT mice but with no effect in PGC-1alpha KO mice. Furthermore, a training-induced
      prevention of an age-associated decline in VEGF protein content was observed in
      WT but not in PGC-1alpha KO muscles. In addition, repeated AICAR treatments
      increased skeletal muscle VEGF protein expression approximately 15% in WT but not
      in PGC-1alpha KO mice. This study shows that PGC-1alpha is essential for exercise
      induced upregulation of skeletal muscle VEGF expression and for a training
      induced prevention of an age-associated decline in VEGF protein content.
      Furthermore, the findings suggest an AMPK-mediated regulation of VEGF expression
      through PGC-1alpha.

PMID- 19401460
TI  - Menstrual cycle alters sympathetic neural responses to orthostatic stress in
      young, eumenorrheic women.
AB  - Sympathetic baroreflex sensitivity (BRS) and muscle sympathetic nerve activity
      (MSNA) responses during early follicular (EF) and midluteal (ML) phases of the
      menstrual cycle are controversial. We hypothesize an augmented sympathetic BRS
      and MSNA response to orthostatic stress during the ML phase of the menstrual
      cycle. MSNA, mean arterial pressure (MAP), and heart rate (HR) were recorded
      during progressive lower body negative pressure (LBNP) (-5, -10, -15, -20, -30,
      and -40 mmHg; 3 min/stage) in 13 healthy, eumenorrheic women (age 21 +/- 1 yr).
      Sympathetic BRS was assessed by examining relations between spontaneous
      fluctuations of diastolic arterial pressure and MSNA at rest and during
      progressive LBNP. Plasma estradiol (42 +/- 6 vs. 112 +/- 12 pg/ml; P < 0.01) and
      progesterone (2 +/- 0 vs. 10 +/- 2 ng/ml; P < 0.04) were elevated during the ML
      phase. Resting MSNA (8 +/- 1 vs. 11 +/- 1 bursts/min), MAP (79 +/- 2 vs. 78 +/- 2
      mmHg), and HR (58 +/- 2 vs. 60 +/- 2 beats/min) were not different during EF and
      ML phases. MSNA and HR increased during progressive LBNP (P < 0.001), and the
      increases in MSNA burst frequency (bursts/min) and HR were similar during both
      phases. In contrast, increases in total MSNA (arbitrary units) during progressive
      LBNP were augmented during the ML phase (P < 0.04), but this response does not
      appear to be linked to differences in sympathetic BRS. Progressive LBNP did not
      change MAP during either phase. Our results demonstrate an augmentation of the
      MSNA response to progressive LBNP during the ML phase of the menstrual cycle.
      These findings suggest that hormonal fluctuations of eumenorrheic women may
      influence sympathoexcitation during an orthostatic challenge, but not through
      sympathetic baroreflex-mediated pathways.

PMID- 19401461
TI  - Structural insights into the interactions between platelet receptors and
      fibrillar collagen.
AB  - Collagen peptides have been used to identify binding sites for several important
      collagen receptors, including integrin alpha(2)beta(1), glycoprotein VI, and von
      Willebrand factor. In parallel, the structures of these collagen receptors have
      been reported, and their interactions with collagen peptides have been studied.
      Recently, the three-dimensional structure of the intact type I collagen fiber
      from rat tail tendon has been resolved by fiber diffraction. It is now possible
      to map the binding sites of platelet collagen receptors onto the intact collagen
      fiber in three dimensions. This minireview will discuss these recent findings and
      their implications for platelet activation by collagen.

PMID- 19401462
TI  - Loss of cardiolipin leads to longevity defects that are alleviated by alterations
      in stress response signaling.
AB  - Perturbation of cardiolipin (CL) synthesis in yeast cells leads to defective
      respiratory chain function and mitochondrial DNA loss, both of which have been
      implicated in aging in mammals. The availability of yeast CL mutants enabled us
      to directly investigate the role of CL synthesis in aging. In this report, we
      show that the replicative life span of pgs1Delta, which lacks both CL and the
      precursor phosphatidylglycerol (PG), was significantly decreased at 30 degrees C.
      The life span of crd1Delta, which has PG but not CL, was unaffected at 30 degrees
      C but reduced at 37 degrees C. Life span extension induced by calorie restriction
      was not affected by the loss of CL. However, mild heat and osmotic stress, which
      extend life span in wild type cells, did not increase longevity in CL mutants,
      suggesting that the stress response is perturbed in these mutants. Consistent
      with this, longevity defects in pgs1Delta were alleviated by down-regulation of
      the high osmolarity glycerol stress response pathway, as well as by promoting
      cell integrity with the osmotic stabilizer sorbitol or via genetic suppression
      with the kre5(W1166X) mutant. These findings show for the first time that
      perturbation of CL synthesis leads to decreased longevity in yeast, which is
      restored by altering signaling through stress response pathways.

PMID- 19401464
TI  - Identification of interaction sites between human betaA3- and alphaA/alphaB
      crystallins by mammalian two-hybrid and fluorescence resonance energy transfer
      acceptor photobleaching methods.
AB  - Our recent study has shown that betaA3-crystallin along with betaB1- and betaB2
      crystallins were part of high molecular weight complex obtained from young, old,
      and cataractous lenses suggesting potential interactions between alpha- and beta
      crystallins (Srivastava, O. P., Srivastava, K., and Chaves, J. M. (2008) Mol.
      Vis. 14, 1872-1885). To investigate this further, this study was carried out to
      determine the interaction sites of betaA3-crystallin with alphaA- and alphaB
      crystallins. The study employed a mammalian two-hybrid method, an in vivo assay
      to determine the regions of betaA3-crystallin that interact with alphaA- and
      alphaB-crystallins. Five regional truncated mutants of betaA3-crystallin were
      generated using specific primers with deletions of N-terminal extension (NT)
      (named betaA3-NT), N-terminal extension plus motif I (named betaA3-NT + I), N
      terminal extension plus motifs I and II (named betaA3-NT + I + II), motif III
      plus IV (named betaA3-III + IV), and motif IV (named betaA3-IV). The mammalian
      two-hybrid studies were complemented with fluorescence resonance energy transfer
      acceptor photobleaching studies using the above described mutant proteins, fused
      with DsRed (Red) and AcGFP fluorescent proteins. The results showed that the
      motifs III and IV of betaA3-crystallin were interactive with alphaA-crystallin,
      and motifs II and III of betaA3-crystallin primarily interacted with alphaB
      crystallin.

PMID- 19401463
TI  - Mitochondrial targeting of cytochrome P450 proteins containing NH2-terminal
      chimeric signals involves an unusual TOM20/TOM22 bypass mechanism.
AB  - Previously we showed that xenobiotic inducible cytochrome P450 (CYP) proteins are
      bimodally targeted to the endoplasmic reticulum and mitochondria. In this study,
      we investigated the mechanism of delivery of chimeric signal containing CYP
      proteins to the peripheral and channel-forming mitochondrial outer membrane
      translocases (TOMs). CYP+33/1A1 and CYP2B1 did not require peripheral TOM70,
      TOM20, or TOM22 for translocation through the channel-forming TOM40 protein. In
      contrast, CYP+5/1A1 and CYP2E1 were able to bypass TOM20 and TOM22 but required
      TOM70. CYP27, which contains a canonical cleavable mitochondrial signal, required
      all of the peripheral TOMs for its mitochondrial translocation. We investigated
      the underlying mechanisms of bypass of peripheral TOMs by CYPs with chimeric
      signals. The results suggested that interaction of CYPs with Hsp70, a cytosolic
      chaperone involved in the mitochondrial import, alone was sufficient for the
      recognition of chimeric signals by peripheral TOMs. However, sequential
      interaction of chimeric signal containing CYPs with Hsp70 and Hsp90 resulted in
      the bypass of peripheral TOMs, whereas CYP27A1 interacted only with Hsp70 and was
      not able to bypass peripheral TOMs. Our results also show that delivery of a
      chimeric signal containing client protein by Hsp90 required the cytosol-exposed
      NH(2)-terminal 143 amino acids of TOM40. TOM40 devoid of this domain was unable
      to import CYP proteins. These results suggest that compared with the unimodal
      mitochondrial targeting signals, the chimeric mitochondrial targeting signals are
      highly evolved and dynamic in nature.

PMID- 19401465
TI  - Structural requirements for the ubiquitin-associated domain of the mRNA export
      factor Mex67 to bind its specific targets, the transcription elongation THO
      complex component Hpr1 and nucleoporin FXFG repeats.
AB  - The ubiquitin-associated (UBA) domain of the principal Saccharomyces cerevisiae
      mRNA nuclear export factor, Mex67, can bind both nuclear pore protein
      (nucleoporin) FG repeats and Hpr1, a component of the TREX.THO complex that
      functions to link transcription and export. Using fluorescence resonance energy
      transfer-based assays, we show here that Hpr1 and the FG repeats interact with
      overlapping binding sites on the Mex67 UBA domain. We present the solution
      structure of the Mex67 UBA domain (UBA-Mex67) complexed with a FXFG nucleoporin
      peptide and define residues engaged in the interaction and those involved in the
      FXFG-induced conformational change. We show by NMR titration that the binding of
      Hpr1 produces analogous changes in chemical shifts in similar regions of the UBA
      domain. Together the data presented here indicate that both Hpr1 and FXFG
      nucleoporins may bind in a similar way to the UBA-Mex67 domain. However, whereas
      binding of Hpr1 allows UBA-Mex67 to interact with tetra-ubiquitin, the complex
      between UBA-Mex67 and FXFG is unable to bind mono- or tetra-ubiquitin, suggesting
      that both substrate binding and also the nature of the substrate may influence
      the affinity of the UBA-Mex67 domain for ubiquitin.

PMID- 19401466
TI  - Retinoic acid activates monoamine oxidase B promoter in human neuronal cells.
AB  - Monoamine oxidase (MAO) B deaminates a number of biogenic and dietary amines and
      plays an important role in many biological processes. Among hormonal regulations
      of MAO B, we have recently found that retinoic acid (RA) significantly activates
      both MAO B promoter activity and mRNA expression in a human neuroblastoma BE(2)C
      cell line. RA activates MAO B promoter in both concentration- and time-dependent
      manners, which is mediated through retinoic acid receptor alpha (RARalpha) and
      retinoid X receptor alpha (RXRalpha). There are four retinoic acid response
      elements (RAREs) as identified in the MAO B 2-kb promoter, and mutation of the
      third RARE reduced RA-induced MAO B promoter activation by 50%, suggesting this
      element is important. Electrophoretic mobility shift analysis and chromatin
      immunoprecipitation assay demonstrated that RARalpha specifically binds to the
      third RARE both in vitro and in vivo. Moreover, transient transfection and
      luciferase assays revealed that Sp1 enhances but not essentially required for the
      RA activation of MAO B through two clusters of Sp1-binding sites in the MAO B
      promoter. RARalpha physically interacts with Sp1 via zinc finger domains in Sp1
      as determined by co-immunoprecipitation assay. Further, RARalpha was shown to be
      recruited by Sp1 and to form a transcriptional regulation complex with Sp1 in the
      Sp1-binding sites of natural MAO B promoter. Taken together, this study provides
      evidence for the first time showing the stimulating effect of RA on MAO B and new
      insight into the molecular mechanisms of MAO B regulation by hormones.

PMID- 19401467
TI  - WNK4 diverts the thiazide-sensitive NaCl cotransporter to the lysosome and
      stimulates AP-3 interaction.
AB  - With-no-lysine kinase 4 (WNK4) inhibits electroneutral sodium chloride
      reabsorption by attenuating the cell surface expression of the thiazide-sensitive
      NaCl cotransporter (NCC). The underlying mechanism for this effect remains poorly
      understood. Here, we explore how WNK4 affects the trafficking of NCC through its
      interactions with intracellular sorting machinery. An analysis of NCC cell
      surface lifetime showed that WNK4 did not alter the net rate of cotransporter
      internalization. In contrast, direct measurements of forward trafficking revealed
      that WNK4 attenuated the rate of NCC surface delivery, inhibiting the anterograde
      movement of cotransporters traveling to the plasma membrane from the trans-Golgi
      network. The response was paralleled by a dramatic reduction in NCC protein
      abundance, an effect that was sensitive to the lysosomal protease inhibitor
      leupeptin, insensitive to proteasome inhibition, and attenuated by endogenous
      WNK4 knockdown. Subcellular localization studies performed in the presence of
      leupeptin revealed that WNK4 enhanced the accumulation of NCC in lysosomes.
      Moreover, NCC immunoprecipitated with endogenous AP-3 complexes, and WNK4
      increased the fraction of cotransporters that associate with this adaptor, which
      facilitates cargo transport to lysosomes. WNK4 expression also increased LAMP-2
      positive lysosomal content, indicating that the kinase may act by a general AP-3
      dependent mechanism to promote cargo delivery into the lysosomal pathway. Taken
      together, these findings indicate that WNK4 inhibits NCC activity by diverting
      the cotransporter to the lysosome for degradation by way of an AP-3 transport
      carrier.

PMID- 19401468
TI  - Otx2 induction of the gonadotropin-releasing hormone promoter is modulated by
      direct interactions with Grg co-repressors.
AB  - Hormonal communication between the hypothalamus, pituitary, and gonads
      orchestrates the development and regulation of mammalian reproductive function.
      In mice, gonadotropin-releasing hormone (GnRH) expression is limited to
      approximately 1000 neurons that originate in the olfactory placode then migrate
      to specific positions scattered throughout the hypothalamus. Coordination of the
      hypothalamic-pituitary-gonadal axis is dependent upon correct migration of GnRH
      neurons into the hypothalamus followed by the appropriate synthesis and pulsatile
      secretion of GnRH. Defects in any one of these processes can cause infertility.
      Recently, substantial progress has been made in identifying transcription
      factors, and their cofactors, that regulate not only adult expression of GnRH,
      but also the maturation of GnRH neurons. Here, we show that expression of Otx2, a
      homeodomain protein required for the formation of the forebrain, is dramatically
      up-regulated during GnRH neuronal maturation and that overexpression of Otx2
      increases GnRH promoter activity in GnRH neuronal cell lines. Furthermore, Otx2
      transcriptional activity is modulated by Grg4, a member of the Groucho-related
      gene (Grg) family. Using mutational analysis, we show that a WRPW peptide motif
      within the Otx2 protein is required for physical interaction between Otx2 and
      Grg4. Without this physical interaction, Grg4 cannot repress Otx2-dependent
      activation of GnRH gene transcription. Taken together, these data show that Otx2
      is important for GnRH expression and that direct interaction between Otx2 and Grg
      co-repressors regulates GnRH gene expression in hypothalamic neurons.

PMID- 19401469
TI  - ENaC at the cutting edge: regulation of epithelial sodium channels by proteases.
AB  - Epithelial Na+ channels facilitate the transport of Na+ across high resistance
      epithelia. Proteolytic cleavage has an important role in regulating the activity
      of these channels by increasing their open probability. Specific proteases have
      been shown to activate epithelial Na+ channels by cleaving channel subunits at
      defined sites within their extracellular domains. This minireview addresses the
      mechanisms by which proteases activate this channel and the question of why
      proteolysis has evolved as a mechanism of channel activation.

PMID- 19401471
TI  - Evaluating the incidence of leukopenia and neutropenia with valproate,
      quetiapine, or the combination in children and adolescents.
AB  - BACKGROUND: At the Austin State Hospital, Austin, TX, a number of cases of
      neutropenia and leukopenia have been observed in children and adolescents who
      were treated with the combination of valproate and quetiapine. Use of this
      combination has raised concerns regarding an increased risk of hematologic
      toxicity. OBJECTIVE: To evaluate the incidence of leukopenia and neutropenia
      associated with the use of valproate, quetiapine, or the combination in the child
      and adolescent population. METHODS: This study was a retrospective evaluation of
      patients from the child and adolescent psychiatric service of the Austin State
      Hospital who were treated with valproate, quetiapine, or the combination.
      Subjects were selected from patients discharged between August 1, 2004, and
      August 31, 2007. Laboratory data were evaluated to determine the incidence and
      severity of leukopenia and neutropenia associated with valproate, quetiapine, and
      a combination of the 2. RESULTS: A total of 131 patients were included in the
      study. Analysis of the laboratory data revealed a combined incidence of
      neutropenia and/or leukopenia of 44%, 26%, and 6% in the combination group,
      valproate monotherapy group, and quetiapine monotherapy group, respectively.
      Differences in the incidence of neutropenia and/or leukopenia between the
      quetiapine monotherapy group and valproate monotherapy group, as well as the
      quetiapine monotherapy group and the combination group reached statistical
      significance. A significant difference was found among groups based on absolute
      neutrophil count Common Toxicity Criteria severity (p < 0.001). The combination
      group differed significantly in incidence of moderate-to-severe neutropenia (14
      cases) from both the valproate (5 cases) and quetiapine (0 cases) monotherapy
      groups. A significantly greater number (44%) of African American patients
      experienced neutropenia and/or leukopenia than white (not Hispanic or Latino;
      29%) or Hispanic or Latino (11%) patients. CONCLUSIONS: Patients treated with
      valproate or the combination of valproate and quetiapine should be monitored for
      the occurrence of leukopenia and neutropenia. Controlled studies are warranted to
      examine possible pharmacokinetic and pharmacodynamic interactions with the
      combination of valproate and quetiapine to further evaluate the hematologic
      findings of this study.

PMID- 19401470
TI  - Exosite determinants of serpin specificity.
AB  - Serpins form an enormous superfamily of 40-60-kDa proteins found in almost all
      types of organisms, including humans. Most are one-use suicide substrate serine
      and cysteine proteinase inhibitors that have evolved to finely regulate complex
      proteolytic pathways, such as blood coagulation, fibrinolysis, and inflammation.
      Despite distinct functions for each serpin, there is much redundancy in the
      primary specificity-determining residues. However, many serpins exploit
      additional exosites to generate the exquisite specificity that makes a given
      serpin effective only when certain other criteria, such as the presence of
      specific cofactors, are met. With a focus on human serpins, this minireview
      examines use of exosites by nine serpins in the initial complex-forming phase to
      modulate primary specificity in either binary serpin-proteinase complexes or
      ternary complexes that additionally employ a protein or other cofactor. A
      frequent theme is down-regulation of inhibitory activity unless the exosite(s)
      are engaged. In addition, the use of exosites by maspin and plasminogen activator
      inhibitor-1 to indirectly affect proteolytic processes is considered.

PMID- 19401472
TI  - Effect of non-ergot dopamine agonists on health-related quality of life of
      patients with restless legs syndrome.
AB  - BACKGROUND: Non-ergot dopamine agonists (NEDAs) have become the gold-standard
      agents for the treatment of restless legs syndrome (RLS). While the efficacy and
      safety of these drugs have been widely studied, their effect on patients' health
      related quality of life (HRQoL) has not been fully elucidated. OBJECTIVE: To
      better define the usefulness of NEDAs by assessing their impact on HRQoL.
      METHODS: We performed a meta-analysis of randomized, double-blind, placebo
      controlled trials evaluating the use of NEDAs in patients with RLS. A systematic
      literature search of MEDLINE, EMBASE, and Cochrane CENTRAL was performed from the
      earliest possible date through July 2008. Trials were included in the analysis if
      they evaluated NEDAs for the treatment of RLS and reported HRQoL using any RLS
      disease-specific HRQoL instrument. HRQoL data were pooled and evaluated using an
      inverse variance weighting approach as standardized mean differences (SMDs) and
      95% confidence interval (CI). For trials reporting HRQoL data obtained using the
      Johns Hopkins RLS-QoL Questionnaire, adjusted mean difference data were pooled to
      calculate the weighted mean difference (WMD) and 95% CI. RESULTS: Seven trials (N
      = 1483) met all inclusion criteria. Patients with RLS taking NEDAs had
      significantly improved overall effect on HRQoL compared with those taking placebo
      (SMD 0.20; 95% CI 0.10 to 0.30; degree of inconsistency across studies [I(2)] =
      0%). When analyzing trials using the Johns Hopkins RLS-QoL questionnaire, the
      results also showed improvement with NEDAs compared with placebo (WMD 4.72; 95%
      CI 2.96 to 6.47; I(2) = 0%). Study conclusions were unchanged upon sensitivity
      analysis. The number of trials for each NEDA was small, limiting the usefulness
      of between-agent comparisons. CONCLUSIONS: In patients with RLS, use of NEDAs
      showed improved HRQoL compared with placebo. Since pooled effect sizes observed
      in this meta-analysis appear to surpass accepted values for minimally important
      clinical differences, these improvements may be clinically relevant for the
      average studied patient. However, future studies evaluating long-term treatment
      of RLS with NEDAs are necessary, as are head-to-head comparative trials and
      economic assessments.

PMID- 19401473
TI  - Effects of Ginkgo biloba extract ingestion on the pharmacokinetics of talinolol
      in healthy Chinese volunteers.
AB  - BACKGROUND: Ginkgo biloba extract (GBE), the best selling herbal medicine in the
      world, has been reported to inhibit P-glycoprotein in vitro. However, the effects
      of GBE on P-glycoprotein activity in humans have not been clarified. OBJECTIVE:
      To investigate the effects of single and repeated GBE ingestion on the oral
      pharmacokinetics of talinolol, a substrate drug for P-glycoprotein in humans.
      METHODS: Ten unrelated healthy male volunteers were selected to participate in a
      3-stage sequential study. Plasma concentrations of talinolol from 0 to 24 hours
      were measured by high-performance liquid chromatography after talinolol 100 mg
      was administrated alone, with a single oral dose of GBE (120 mg), and after 14
      days of repeated GBE ingestion (360 mg/day). RESULTS: A single oral dose of GBE
      did not affect the pharmacokinetics of talinolol. Repeated ingestion of GBE
      increased the talinolol maximum plasma concentration (C(max)) by 36% (90% CI 10
      to 68; p = 0.025), the area under the concentration-time curve (AUC)(0-24) by 26%
      (90% CI 11 to 43; p = 0.008) and AUC(0-infinity) by 22% (90% CI 8 to 37; p =
      0.014), respectively, without significant changes in elimination half-life and
      the time to C(max). CONCLUSIONS: Our results suggest that long-term use of GBE
      significantly influenced talinolol disposition in humans, likely by affecting the
      activity of P-glycoprotein and/or other drug transporters.

PMID- 19401474
TI  - Romiplostim management of immune thrombocytopenic purpura.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of
      romiplostim, the first drug approved for use in patients with immune
      thrombocytopenic purpura (ITP). DATA SOURCES: Articles were identified through
      searches of MEDLINE (1966-January 2009) and International Pharmaceutical
      Abstracts (1970-January 2009) using the key words romiplostim and AMG 531.
      Searches were limited to articles published in English. The manufacturer was
      contacted for additional data. STUDY SELECTION AND DATA EXTRACTION: Clinical
      trials and pharmacokinetic data were selected for review. DATA SYNTHESIS:
      Romiplostim is a second-generation thrombopoietic receptor agonist that exerts
      its therapeutic effect by stimulating megakaryopoiesis. Subcutaneous therapy
      results in a dose-dependent increase in platelets; however, interindividual
      variability exists. Time to peak concentration is approximately 14 hours, and the
      elimination half-life is approximately 3.5 days (range 1-34). Romiplostim
      undergoes endothelial recirculation and is eliminated by the reticuloendothelial
      system. The results of 2 Phase 3, randomized, double-blind, placebo-controlled
      trials have demonstrated the efficacy of romiplostim for increasing platelet
      counts in patients with ITP refractory to other therapies, including splenectomy.
      Effects on platelets were transient and decreased within 2 weeks of discontinuing
      the drug. Interim results of an open-label extension study revealed that
      romiplostim has sustained efficacy and tolerability for up to 156 weeks at a
      dosage range of 1-17 microg/kg/wk (mean 5.9 +/- 3.9). The most common adverse
      effects include headache, fatigue, epistaxis, and contusion. Romiplostim is also
      under investigation for treatment of thrombocytopenia associated with
      myelodysplastic syndrome. The drug must be ordered directly from the manufacturer
      through a limited access program, and weekly subcutaneous injections are given in
      the clinic setting. CONCLUSIONS: Romiplostim is effective for the management of
      ITP in adults refractory to other therapies, including splenectomy.

PMID- 19401475
TI  - Prevalence of use and the risk of adverse effects associated with complementary
      and alternative medicine in a cohort of patients receiving warfarin.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM), including
      orally administered herbals, botanicals, vitamins, and supplements, may pose a
      risk to patients on warfarin therapy. OBJECTIVE: To estimate the prevalence of
      CAM use among patients taking warfarin and evaluate the impact of CAM exposure on
      the risk of warfarin-related adverse effects. METHODS: A survey was administered
      to hospital inpatients and clinic outpatients on drug exposure (including CAM)
      over the previous month, self-reported bleeding events, use of alcohol and
      vitamin K-rich foods, and medical conditions. Prescription medication use was
      verified, and laboratory records were checked for out-of-range international
      normalized ratios (INRs) (defined as INR >4 or <2). The use of CAM, including
      products with reported or theoretical interactions with warfarin, was compared
      between patients with and without self-reported bleeding or out-of-range INR.
      RESULTS: Among the 314 patients who completed the survey, 44.3% reported using
      CAM at least weekly. Potentially interacting CAM was used by 34.1% of all
      patients, or 18.2% if vitamin E was excluded as an interacting CAM. Vitamin E was
      used by 24.2% of all patients and 71.0% of those who used potentially interacting
      CAM. There was no significant difference in CAM use or consumption of vitamin K
      rich foods between patients with and without INRs greater than 4 or for patients
      with and without INRs less than 2. CONCLUSIONS: The use of potentially
      interacting CAM in this cohort was higher than the use previously reported among
      patients on warfarin therapy. However, exposure to CAM was not associated with an
      increase in the risk of self-reported bleeding or out-of-range INR.

PMID- 19401476
TI  - Clinical evidence of interaction between itraconazole and nonnucleoside reverse
      transcriptase inhibitors in HIV-infected patients with disseminated
      histoplasmosis.
AB  - BACKGROUND: Itraconazole is the preferred drug for chronic maintenance therapy in
      HIV-infected patients with disseminated histoplasmosis. Unfortunately, few
      clinical data exist confirming a presumed interaction between itraconazole and
      nonnucleoside reverse transcriptase inhibitors (NNRTIs). OBJECTIVE: To determine
      whether serum itraconazole concentrations are affected by the type of
      antiretroviral therapy (NNRTI or protease inhibitor [PI]) being taken
      concomitantly. METHODS: This retrospective cohort identified patients on
      antiretroviral therapy and itraconazole for disseminated histoplasmosis between
      January 2003 and December 2006 at a large HIV clinic in Houston, TX. Available
      laboratory values were abstracted from medical records. RESULTS: Thirteen
      itraconazole concentrations from 10 patients were available for analysis: 7
      patients were on concomitant PIs, 4 on concomitant NNRTIs, and 2 on
      antiretroviral regimens containing both PIs and NNRTIs. Six of the itraconazole
      concentrations during concomitant PI treatment were therapeutic (>1.0 microg/mL),
      in contrast with none in patients taking an NNRTI. All patients taking
      concomitant NNRTIs had undetectable serum itraconazole concentrations (<0.05
      microg/mL). Two patients switched from NNRTI-based to PI-based antiretroviral
      regimens and subsequently reached therapeutic itraconazole concentrations.
      Although limited by small sample size, this study provides the largest clinical
      data among HIV-infected patients demonstrating that coadministration of an NNRTI
      and itraconazole results in significant decreases in itraconazole blood
      concentrations, likely by inducing the CYP3A4 enzyme system. CONCLUSIONS:
      Itraconazole concentrations should be monitored in patients taking concomitant
      NNRTIs. PI-based highly active antiretroviral therapy (HAART) may be preferred
      over NNRTI-based HAART when itraconazole is used to treat HIV-infected patients
      with disseminated histoplasmosis.

PMID- 19401477
TI  - Community pharmacist-provided extended diabetes care.
AB  - BACKGROUND: Pharmacists in various settings have been effective in initiating
      diabetes treatment. Patients with diabetes require ongoing disease management,
      and community pharmacists are in a strategic position to provide such extended
      care. Little is known, however, about the effects of community pharmacist
      provided interventions beyond the initial treatment period. OBJECTIVE: To
      evaluate the effect of community pharmacist-provided extended diabetes care
      service on primary clinical outcomes, including hemoglobin A(1c) (A1C), low
      density lipoprotein cholesterol (LDL-C), and blood pressure, and on patients'
      reported self-care activities. METHODS: A randomized controlled trial was
      conducted in patients with diabetes. Participants had already completed at least
      2 diabetes education sessions at a local diabetes education center. Nine
      specially trained pharmacists administered interventions during up to 4 quarterly
      visits per patient. Interventions included discussing medications, clinical
      goals, and self-care activities with patients and recommending medication changes
      to physicians when appropriate. The main outcome measures were 12-month changes
      in A1C, LDL-C, blood pressure, and self-report of self-care activities. RESULTS:
      Seventy-eight patients participated in the study (36 intervention, 42 control);
      66 were included in the final analysis (31 intervention, 35 control). Compared
      with changes in the control group, patients who received interventions
      significantly increased the number of days per week that they engaged in a set of
      diet and diabetes self-care activities (1.25 and 0.73 more days/wk,
      respectively). The mean 12-month changes for A1C, LDL-C, and blood pressure were
      not significantly different between the 2 study groups. CONCLUSIONS: Although
      pharmacist-provided interventions did not demonstrate statistically significant
      improvements in clinical outcomes over the study period, study results did show
      that pharmacists were effective at increasing the number of days that patients
      spent engaging in healthy diet and diabetes self-care activities. Addressing
      lifestyle and self-care behaviors can be a beneficial component of a pharmacist
      provided extended diabetes care service.

PMID- 19401478
TI  - Role of metformin in the treatment of gestational diabetes.
AB  - OBJECTIVE: To evaluate the safety and efficacy of metformin in the treatment of
      gestational diabetes mellitus (GDM). DATA SOURCES: A literature search was
      conducted via PubMed (1948-December 2008), International Pharmaceutical Abstracts
      (1970-December 2008), and Cochrane Library (up to 2008) using the search terms
      gestational diabetes and metformin. No limits were applied to the search.
      Reference citations from relevant publications identified were also reviewed.
      STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data
      sources were reviewed for inclusion. Original research and retrospective cohorts
      were included in the review. Thirty-three articles were selected for review; 6
      met the inclusion criteria. Trials evaluating the use of metformin in pregnant
      women with polycystic ovarian syndrome were not included. DATA SYNTHESIS:
      Metformin has been found largely to be effective in the treatment of GDM. One
      retrospective study reported that preeclampsia and neonatal mortality are
      increased with the use of metformin. The largest randomized trial to date found
      that neonatal and maternal complications did not differ between patients treated
      with metformin and those treated with insulin; however, rates of preterm birth
      were increased in the metformin group. In all studies reviewed, patients treated
      with metformin tended to be overweight or obese and required varying doses of
      metformin. CONCLUSIONS: Metformin appears to be effective for the treatment of
      GDM, but safety concerns may limit its use. Due to these concerns, insulin should
      remain the drug of choice if dietary measures alone fail.

PMID- 19401479
TI  - Telavancin: a novel lipoglycopeptide antibiotic.
AB  - OBJECTIVE: To review the pharmacology, antimicrobial activity, pharmacokinetics,
      clinical applications, and safety of telavancin, a new lipoglycopeptide
      antibiotic. DATA SOURCES: Literature was obtained from MEDLINE (1966-April 2009)
      and International Pharmaceutical Abstracts (1971-April 2009) using the search
      terms telavancin and TD-6424, and also from Theravance, Inc., and Astellas Pharma
      US, Inc. STUDY SELECTION AND DATA EXTRACTION: Available English-language articles
      were reviewed, as well as information obtained from Theravance, Inc., and
      Astellas Pharma US, Inc. DATA SYNTHESIS: Telavancin has rapid bactericidal
      activity against gram-positive aerobic and anaerobic bacteria through multiple
      mechanisms of action. In vitro and Phase 2 in vivo data support the efficacy of
      telavancin against antibiotic-resistant gram-positive organisms. On March 4,
      2008, the Food and Drug Administration (FDA) accepted as complete for review
      Theravance's response to the October 19, 2007, New Drug Application approvable
      letter for telavancin to be used as treatment for complicated skin and skin
      structure infections (cSSSIs) caused by gram-positive bacteria. QTc interval
      prolongation has been reported, although the clinical impact of this has not been
      determined. Drug interactions have not been identified as of yet. CONCLUSIONS:
      Telavancin is currently under review by the FDA for the treatment of cSSSIs
      caused by gram-positive bacteria. The completion of Phase 3 trials will determine
      whether telavancin will have a role in the treatment of other infections caused
      by resistant gram-positive bacteria.

PMID- 19401480
TI  - Biofilms, infection, and parenteral nutrition therapy.
AB  - Parenteral nutrition therapy is used in patients with a contraindication to the
      use of the gastrointestinal tract, and infection is one of its frequent and
      severe complications. The objective of the present study was to detect the
      presence of biofilms and microorganisms adhering to the central venous catheters
      used for parenteral nutrition therapy by scanning electron microscopy. Thirty
      nine central venous catheters belonging to patients with clinical signs of
      infection (G1) and asymptomatic patients (G2) and patients receiving central
      venous catheters for clinical monitoring (G3) were analyzed by semiquantitative
      culture and scanning electron microscopy. The central venous catheters of G1
      presented more positive cultures than those of G2 and G3 (81% vs 50% and 0%,
      respectively). However, biofilms were observed in all catheters used and 55% of
      them showed structures that suggested central venous catheters colonization by
      microorganisms. Approximately 53% of the catheter infections evolved with
      systemic infection confirmed by blood culture. The authors conclude that the
      presence of a biofilm is frequent and is an indicator of predisposition to
      infection, which may even occur in patients who are still asymptomatic.

PMID- 19401481
TI  - Tackling asthma phenotypes in community studies.

PMID- 19401482
TI  - The art of replication.

PMID- 19401483
TI  - Change in smoking status after low-dose spiral chest CT screening for lung
      cancer: opportunity for smoking intervention.

PMID- 19401484
TI  - Sex, cough and (digital) audiotape.

PMID- 19401486
TI  - Bilateral pneumothoraces, cystic lung disease and papular skin lesions in a young
      man.

PMID- 19401489
TI  - Familial idiopathic pulmonary fibrosis in association with bone marrow hypoplasia
      and hepatic nodular regenerative hyperplasia: a new "trimorphic" syndrome.
AB  - This is the first report of familial idiopathic pulmonary fibrosis associated
      with hepatic nodular regenerative hyperplasia and bone marrow hypoplasia. Four
      members of one family presented with this triad of organ dysfunction. The
      response to immunosuppressive treatment was poor and all four members succumbed
      to the disease processes. The current literature is reviewed and mechanisms that
      could have been involved in the development of this new syndrome are proposed.

PMID- 19401490
TI  - The airway vasculature: recent advances and clinical implications.
AB  - It is increasingly recognised that the airway circulation plays an important role
      in airway diseases, either through a change in blood flow or through
      microvascular leakage. Most of the information available regarding the anatomy
      and physiology of bronchial blood flow and its regulation has necessarily derived
      from animal studies. However, there have recently been important advances in
      understanding airway blood flow in airway disease in humans through the
      development of non-invasive methods and in the quantification of microvascular
      leakage using plasma markers. These studies have shown that bronchial blood flow
      is increased in patients with asthma but not in those with chronic obstructive
      pulmonary disease, confirming previous pathology investigations. Changes in
      bronchial blood flow may in part reflect the generation of new vascular vessels,
      a process known as "angiogenesis" which is caused by airway inflammation.
      Angiogenesis and the resulting plasma leak affect airway physiology, drug
      clearance and its bioavailability. This review discusses the anatomy, physiology
      and regulation of bronchial blood flow in the normal and diseased lung, In
      addition, it analyses the effect of current medical treatment and discusses the
      potential use of new anti-angiogenesis medications. The development of non
      invasive assessment of bronchial blood flow and the study of angiogenesis have
      provided a tool to investigate airway physiology in vivo; these advances will
      contribute to a better understanding of inflammatory airway diseases as well as
      the implication of these findings to management.

PMID- 19401491
TI  - Retinoid induction of alveolar regeneration: from mice to man?
AB  - The use of retinoids to induce human lung regeneration is under investigation in
      a number of studies in patients with chronic obstructive pulmonary disease
      (COPD). Retinoic acid (RA) has complex pleiotropic functions during vertebrate
      patterning and development and can induce regeneration in a number of different
      organ systems. Studies of retinoid signalling during lung development might
      provide a molecular basis to explain pharmacological induction of alveolar
      regeneration in adult models of lung disease. In this review the role of
      endogenous RA signalling during alveologenesis is explored and data suggesting
      that a number of exogenous retinoids can induce regeneration in the adult lung
      are discussed. Current controversies in this area are highlighted and a
      hypothesis of lung regeneration is put forward. Understanding the cellular and
      molecular mechanisms of induction of regeneration will be central for effective
      translation into patients with lung disease and may reveal novel insights into
      the pathogenesis of alveolar disease and senescence.

PMID- 19401493
TI  - Quantifying physical activity in COPD: different measures for different purposes.

PMID- 19401494
TI  - Non-atopic persistent asthma in children.

PMID- 19401495
TI  - New diagnosis and subsequent post-partum radiological improvement of
      lymphangioleiomyomatosis.

PMID- 19401497
TI  - Mechanisms of growth inhibition in human papillomavirus positive and negative
      cervical cancer cells by the chloromethyl ketone protease inhibitor, succinyl
      alanine-alanine-proline-phenylalanine chloromethyl ketone.
AB  - The chymotrypsin-like serine protease inhibitor, succinyl-alanine-alanine-proline
      phenylalanine chloromethyl ketone (AAPF(CMK)), has been shown to have
      anticarcinogenic activity in a number of model systems and to be relatively
      selective for a nuclear protease. This inhibitor also has substantial effects on
      growth of tumorigenic human papillomavirus (HPV)-infected keratinocytes in
      organotypic raft cultures. Here, we examined the effects of AAPF(CMK) on cell
      growth, cell-cycle kinetics, apoptosis induction, and DNA synthesis in two human
      cervical carcinoma cell lines: SiHa cells, which have integrated high-risk HPV
      16; and C33a cells, which do not contain HPV DNA. AAPF(CMK) inhibited growth of
      both cell lines in a time- and dose-dependent manner. Apoptosis studies showed no
      significant difference in drug-treated versus vehicle-treated cells in the C33a
      cell line. However, a significant dose-dependent increase in apoptosis occurred
      at a late time point in SiHa cells. Cell-cycle progression and DNA synthesis
      assays showed that the cellular mechanisms of growth inhibition by AAPF(CMK)
      differ between the HPV16-positive and HPV-negative tumorigenic cell lines. Drug
      treated C33a cells showed a significant accumulation of cells in the G(2) phase
      of the cell cycle. In SiHa cells, growth inhibition produced by AAPF(CMK) seemed
      to result from a global arrest of the cell cycle. Although the molecular
      mechanisms involved in AAPF(CMK)-induced growth inhibition are distinct between
      the two tumorigenic cell lines, such differences may ultimately prove to have
      therapeutic utility. Novel therapies for treating established HPV infections are
      needed, because HPV is a causative agent in the development of multiple types of
      cancer.

PMID- 19401498
TI  - Benchmarking nursing home performance at the state level.
AB  - This paper reports the results of a state-level comparison of the performance of
      nursing homes. The results were obtained by applying data envelopment analysis
      (DEA) to data (obtained from OSCAR, the online survey, certification and
      reporting database [2004]) for all the skilled nursing facilities in each of the
      50 states and the District of Columbia. DEA produces an efficiency score for each
      state that can serve as a single comprehensive measure of its overall
      performance. However, two DEA models were used in the analysis reported here so
      that each state could be given two efficiency scores, one for each of the two
      aspects of their performance - quality efficiency and operating efficiency.
      Eleven states were identified as being 100% efficient for both quality and
      operating efficiency of their nursing homes. For the remaining states (i.e. those
      having lower scores for either quality efficiency or operating efficiency or
      both), DEA results include, in addition to the efficiency score, performance
      goals and a benchmark set of other states that could be used as models of 'best
      practice'.

PMID- 19401496
TI  - [N-methyl-3H3]AZ10419369 binding to the 5-HT1B receptor: in vitro
      characterization and in vivo receptor occupancy.
AB  - Radiotracers suitable for positron emission tomography studies often serve as
      preclinical tools for in vivo receptor occupancy. The serotonin 1B receptor (5
      HT(1B)) subtype is a pharmacological target used to discover treatments for
      various psychiatric and neurological disorders. In psychiatry, 5-HT(1B)
      antagonists may provide novel therapeutics for depression and anxiety. We report
      on the in vitro and in vivo evaluation of tritiated 5-methyl-8-(4-methyl
      piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylicacid (4-morpholin-4-yl-phenyl)
      amide ([N-methyl-(3)H(3)]AZ10419369), a potent 5-HT(1B) radiotracer. [N-methyl
      (3)H(3)]-AZ10419369 showed saturable single-site high-affinity in vitro binding
      (guinea pig, K(d) = 0.38 and human, K(d) = 0.37) to guinea pig or human 5-HT(1B)
      receptors in recombinant membranes and high-affinity (K(d) = 1.9 nM) saturable
      (B(max) = 0.099 pmol/mg protein) binding in membranes from guinea pig striatum.
      When [N-methyl-(3)H(3)]AZ10419369 was administered to guinea pigs by intravenous
      bolus, the measured radioactivity was up to 5-fold higher in brain areas
      containing the 5-HT(1B) receptor (striatum/globus pallidus, midbrain,
      hypothalamus, and frontal cortex) compared with the cerebellum, the nonspecific
      binding region. Specific uptake peaked 30 min after injection with slow
      dissociation from target regions, as suggested by the in vitro binding kinetic
      profile. Pretreatment with 6-fluoro-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene
      2-carboxylic acid [4-(4-propionyl-piperazin-1-yl)-phenyl]-amide (AZD1134) and 2
      aminotetralin (AR-A000002), 5-HT(1B)-selective ligands, inhibited [N-methyl
      (3)H(3)]AZ10419369-specific binding in a dose-dependent manner. In the guinea pig
      striatum, AZD1134 (ED(50) = 0.017 mg/kg) occupies a greater percentage of the 5
      HT(1B) receptors at a lower administered dose than AR-A000002 (ED(50) = 2.5
      mg/kg). In vivo receptor occupancy is an essential component to build binding
      efficacy-exposure relationships and compare novel compound pharmacology. [N
      methyl-(3)H(3)]AZ10419369 is a useful preclinical tool for investigating 5-HT(1B)
      receptor occupancy for novel compounds targeting this receptor.

PMID- 19401499
TI  - The influence of facility ownership structure on individual responding to stress:
      a multilevel model.
AB  - Few studies have investigated the effect of health-care facility ownership on the
      relationship between patient stressors and coping strategies. The purpose of this
      study was to investigate whether haemodialysis (HD) patient stressors and coping
      strategies differ by type of health-care facility ownership, and whether such
      ownership has a cross-level moderating effect between stressors and coping
      strategies. We used the Haemodialysis Stressor Scale and the Jalowiec Coping
      Scale; primary data were collected by interviewing 2642 HD patients 15 years or
      older on dialysis for at least three months from 27 HD centres. One-way analysis
      of variance and hierarchical linear modelling were used to attain the research
      purposes. HD patients from religious-based hospitals had higher stress related to
      their physical symptoms, dependency on medical staff, role ambiguity and blood
      vessel problems than those differently owned facilities. Patients in veterans and
      army (VA) hospitals had higher stress related to food and fluid restriction and
      dependency on medical staff than private centres. Patients in religious-based
      hospitals had significantly higher coping scores, followed by VA and private HD
      centres. Religion-based ownership might serve as a cross-level moderator for
      patients perceiving role ambiguity stress and using problem-oriented, support
      seeking and isolated thought-coping strategies.

PMID- 19401500
TI  - Systems thinking, complexity and managerial decision-making: an analytical
      review.
AB  - One feature that characterizes the organization and delivery of health care is
      its inherent complexity. All too often, with so much information and so many
      activities involved, it is difficult for decision-makers to determine in an
      objective fashion an appropriate course of action. It would appear that a
      holistic rather than a reductionist approach would be advantageous. The aim of
      this paper is to review how formal systems thinking can aid decision-making in
      complex situations. Consideration is given as to how the use of a number of
      systems modelling methodologies can help in gaining an understanding of a complex
      decision situation. This in turn can enhance the possibility of a decision being
      made in a more rational, explicit and transparent fashion. The arguments and
      approaches are illustrated using examples taken from the public health arena.

PMID- 19401501
TI  - A conceptual framework for selecting the most appropriate variables for measuring
      hospital efficiency with a focus on Iranian public hospitals.
AB  - Over the past few decades, there has been an increasing interest in the
      measurement of hospital efficiency in developing countries and in Iran. While the
      choice of measurement methods in hospital efficiency assessment has been widely
      argued in the literature, few authors have offered a framework to specify
      variables that reflect different hospital functions, the quality of the process
      of care and the effectiveness of hospital services. However, without the
      knowledge of hospital objectives and all relevant functions, efficiency studies
      run the risk of making biased comparisons, particularly against hospitals that
      provide higher quality services requiring the use of more resources. Undertaking
      an in-depth investigation regarding the multi-product nature of hospitals,
      various hospital functions and the values of various stakeholders (patient, staff
      and community) with a focus on the Iranian public hospitals, this study has
      proposed a conceptual framework to select the most appropriate variables for
      measuring hospital efficiency using frontier-based techniques. This paper
      contributes to hospital efficiency studies by proposing a conceptual framework
      and incorporating a broader set of variables in Iran. This can enhance the
      validity of hospital efficiency studies using frontier-based methods in
      developing countries.

PMID- 19401502
TI  - Innovations in coaching and mentoring: implications for nurse leadership
      development.
AB  - This longitudinal study sought to examine ways in which coaching and mentoring
      relationships impact on the professional development of nurses in terms of career
      and leadership behaviours, and evaluating the differences and similarities
      between those coaching and mentoring relationships. According to the UK
      government, leadership in nursing is essential to the improvement of service
      delivery, and the development and training of all nurses is vital in achieving
      effective change. A coaching and mentoring programme was used to explore the
      comparative advantages of these two approaches for the leadership development of
      nurses in acute, primary care and mental health settings. A longitudinal in-depth
      study was conducted to measure differences and similarities between the mentoring
      and coaching process as a result of a six-month coaching/mentoring programme.
      Five nurses from six UK Health Care Trusts were allocated to a coaching group (n
      = 15) or a mentoring group (n = 15), these were coached or mentored by a member
      of the senior directorate from their own Trust. Qualitative and quantitative data
      were collected at three time points (T1 = baseline, T2 = 4 months and T3 = 9
      months) using semi-structured interviews and questionnaires. While mentoring was
      perceived to be 'support' and coaching was described as 'action', descriptions of
      the actual process and content were quite similar. However, while both groups
      reported significant development in terms of career development, leadership
      skills and capabilities, mentees reported the highest level of development with
      significantly higher scores in eight areas of leadership and management and in
      three areas of career impact. Implications for nurses and health services are
      discussed.

PMID- 19401503
TI  - Optimal designs for 2-color microarray experiments.
AB  - Statisticians can play a crucial role in the design of gene expression studies to
      ensure the most effective allocation of available resources. This paper considers
      Pareto optimal designs for gene expression studies involving 2-color microarrays.
      Pareto optimality enables the recommendation of designs that are particularly
      efficient for the effects of most interest to biologists. This is relevant in the
      microarray context where analysis is typically carried out separately for those
      effects. Our approach will allow for effects of interest that correspond to
      contrasts rather than solely considering parameters of the linear model. We
      further develop the approach to cater for additional experimental considerations
      such as contrasts that are of equal scientific interest. This amounts to
      partitioning all relevant contrasts into subsets of effects that are of equal
      importance. Based on the partitions, a penalty is employed in order to recommend
      designs for complex and varied microarray experiments. Finally, we address the
      issue of gene-specific dye bias. We illustrate using studies of leukemia and
      breast cancer.

PMID- 19401504
TI  - Predicting response of ADHD symptoms to methylphenidate treatment based on
      comorbid anxiety.
AB  - OBJECTIVE: In this small pilot study, the association of comorbid anxiety with
      the treatment of ADHD is studied. METHODS: Eighteen volunteers from a pediatric
      clinic are tested for ADHD and anxiety and assessed for behavioral and cognitive
      ADHD symptomology. Response to methylphenidate as treatment for ADHD symptoms is
      measured 2 to 3 weeks, and again 4 to 6 weeks following the diagnosis of ADHD.
      RESULTS: Methylphenidate proves effective for treating ADHD symptoms (both
      behavioral and cognitive). Participants are categorized into two groups, those
      with ADHD and comorbid anxiety and those with ADHD alone. Behaviorally, no
      statistically significant differences are seen in response between the two
      groups; however; cognitively, the non-anxious group improves significantly more
      than the anxious group. CONCLUSION: Although anxiety may not affect behavioral
      response to stimulant medication in ADHD, it does appear to affect the medication
      response of more subtle symptoms of cognitive performance in ADHD patients.

PMID- 19401506
TI  - Reading Livingstone.

PMID- 19401507
TI  - George Higoumenakis (1895-1983): Greek dermatologist.
AB  - This paper describes the Higoumenakis sign, enlargement of the sternal end of the
      clavicle in patients with late congenital syphilis and the dermatologist after
      whom it is named. Several professors and doctors from the Medical School of the
      University of Athens opposed his actions especially at the University in Greece.
      His persistence led him to productive scientific activity in syphilis,
      leishmaniasis and psoriasis. He became a member of the Greek Parliament from 1964
      to 1967 and eventually Minister of Hygiene - even though this may have been an
      imprudent political choice, due to the unstable socio-political status of that
      period. He died on 27 December 1983 at the age of 88.

PMID- 19401508
TI  - Dr Lazar Remen (1907-74): a forgotten pioneer in the treatment of myasthenia
      gravis.
AB  - Dr Lazar Remen (1907-74) was the first, in 1932, to describe the beneficial
      effect of prostigmine on a myasthenia gravis patient. His observation actually
      preceeded by two years Mary Broadfoot Walker's (1888-1974) paper, which is
      considered to be the landmark article on this association.

PMID- 19401509
TI  - Natan 'Nikolai' Abramovich Vigdorchik (1874-1954): social activism and public
      health in early 20th-century Russia.
AB  - Virtually unknown in the West, the physician Nikolai Vigdorchik is recognized in
      Russian-Soviet history for his role in introducing social security into Russia.
      He rose from Jewish working-class origins to a career that combined activism in
      labour rights and public health with extensive and path-breaking publications in
      social security, occupational safety and public health. He contributed more than
      30 years of leadership to Soviet research and educational institutions devoted to
      occupational safety and health. Vigdorchik's 1935 publication on lead and
      hypertension is illustrative of his contribution to modern epidemiological
      methods, describing a statistical bias in the study of hospitalized patients. It
      predates by 11 years Joseph Berkson's paper, after whom the bias is named.
      Vigdorchik's life illustrates a modern-day conundrum: social activism comes with
      political cost -- by virtue of its evidence-based orientation, public health
      science is safer but both are necessary to move a culture towards health and
      stability.

PMID- 19401510
TI  - John Aitken's chain saw.

PMID- 19401511
TI  - Alfred Francois Donne (1801-78): a pioneer of microscopy, microbiology and
      haematology.
AB  - Alfred Francois Donne is widely known in the scientific community as the
      discoverer of Trichomonas vaginalis, since he was the first to illustrate the
      parasite that later was recognized to cause vaginal infections. However, his
      other, less-known findings are equally important: he was also the inventor of the
      photoelectric microscope, with the assistance of his student Leon Foucault, as
      well as the first to apply photography to microscopic preparations
      (Daguerreotype). His research in microscopy extended to almost all human fluids
      that could be investigated and culminated in his famous Atlas, which was
      illustrated with numerous photographs. Donne was also the first to describe the
      microscopic appearances of leukaemia based on blood preparations acquired from
      patients. Finally, his work in the hygiene of child upbringing and nutrition is
      very significant.

PMID- 19401512
TI  - Look but do not fix: the pioneers of interventional cardiovascular radiology.
AB  - The extension of endovascular radiological procedures to a one-stop combined
      investigation and treatment of cardiovascular disease has revolutionized clinical
      practice. The giants in this respect are Charles Dotter, working from Portland,
      OR; Mason Sones from the Cleveland Clinic; and Andreas Gruentzig from Zurich and
      latterly Atlanta, GA. Serendipity and lateral thinking were pivotal in developing
      procedures that are now routine.

PMID- 19401513
TI  - What motivated Dr David Livingstone (1813-73) in his work in Africa?
AB  - Born of humble beginnings in a Scottish mill-town, David Livingstone would become
      one of the great explorers of the 19th century, traversing 30,000 miles of
      unknown Africa. His pioneering spirit and inquisitive mind brought knowledge and
      discoveries in the fields of tropical medicine, linguistics, botany, zoology,
      anthropology and geology. While it can be argued that Livingstone exhibited
      contradictions and shortcomings as a man, he nonetheless grasped the imagination
      of Victorian Britain and helped to change European attitudes towards Africa
      forever. His numerous endeavours were undertaken under the banner of divinely
      inspired missionary work -- 'If God has accepted my service, then my life is
      charmed till my work is done' (Livingstone D. Livingstone's Private Journals,
      1851-53. London: Chatto & Windus, 1960:108). Yet whether it was indeed religion
      that truly motivated Livingstone, or rather that he used it as a vehicle for his
      other passions, is less certain.

PMID- 19401514
TI  - Samuel Alderman Lomas (1838-1901) the man with two gravestones, his brother
      Muscot Atkin Lomas (1840-1907) and their lives in Victorian asylums.
AB  - Samuel Alderman Lomas died in the Hertfordshire County Asylum, Hill End, St
      Albans in 1901. He was buried in the asylum cemetery where two gravestones bear
      his name. This paper traces his life history and that of his brother Muscot Atkin
      Lomas. Both were classed as idiots in Victorian society and spent most of their
      lives -- from childhood until death -- in asylums.

PMID- 19401516
TI  - Dr Edward Wilson (1872-1912): Antarctic hero.
AB  - Edward Wilson was an artist, doctor, naturalist and explorer. He was on both
      Scott's Antarctic expeditions of the early 1900s, as Junior Surgeon and Zoologist
      on the Discovery expedition of 1901 and as Chief of Scientific Staff on the Terra
      Nova expedition of 1910. He reached the Pole with Scott in 1912 and died with him
      on their ill-fated return from the Pole.

PMID- 19401515
TI  - Kaethe Kollwitz (1867-1945): the artist who may have suffered from Alice in
      Wonderland Syndrome.
AB  - Kaethe Kollwitz was a 20th century German artist who grew to fame for her socio
      political impressions of Germany during World Wars I and II. In her diary,
      Kollwitz self-described symptoms of Alice in Wonderland Syndrome during her
      childhood. She complained of episodes where objects appeared to grow larger or
      smaller and perceptual distortions where she felt she was diminishing in size.
      This may explain why Kollwitz's artistic style appeared to shift from naturalism
      to expressionism, and why her artistic subjects are often shaped with large hands
      and faces. The distortion present in her visual art may have less to do with a
      deliberate emphasis of the artist's feelings and more to do with her perceptual
      experience.

PMID- 19401517
TI  - Sir James Edward Smith (1759-1828) MD FRS, botanist, co-founder of the Linnean
      Society of London.
AB  - James Edward Smith's interest in botany led him to enter medicine at Edinburgh in
      1781. Smith was continuing his medical studies in London when Sir Joseph Banks
      (1743-1820) suggested to him that he should purchase the collection of the famous
      Swedish naturalist Carl Linnaeus that had just been offered to Banks. Smith
      bought the Linnean Collection and Library in 1784. In 1786 he was awarded the
      degree of Doctor of Medicine from Leiden. In 1788 Smith, with two associates,
      founded the Linnean Society of London and became President for life. Smith turned
      from medicine to natural history as a lecturer and writer. During his lifetime he
      produced numerous botanical works of high value, including The English Flora
      (1824-28), and he did much to popularize botany.

PMID- 19401519
TI  - Memorials: Hodgkin's tomb in Jaffa.

PMID- 19401518
TI  - Where Ronald Ross (1857-1932) worked: the discovery of malarial transmission and
      the Plasmodium life cycle.

PMID- 19401520
TI  - Iron chelation directed against biofilms as an adjunct to conventional
      antibiotics.

PMID- 19401521
TI  - The impact of consenter characteristics and experience on patient interest in
      clinical research.
AB  - BACKGROUND: To explain the historically low rates of participation in cancer
      clinical trials, several factors have been studied. These include subject
      characteristics and attitudes, clinical trial availability and eligibility
      criteria, and physician attitudes and communication skills. However, the impact
      of nonphysician research personnel, who often consent patients for studies, is
      unclear. We therefore evaluated the association between consenter characteristics
      and subject interest in clinical research. METHODS: We performed a retrospective
      review of subjects enrolled in a university-based cancer center tissue
      repository. During enrollment, subjects were asked if they were willing to be
      contacted in the future to (a) provide medical follow-up information and (b)
      participate in other clinical research. We analyzed the association between
      responses to these questions and consenter characteristics using univariate
      analysis and multivariate logistic regression. RESULTS: In total, 181 consenters
      enrolled 922 subjects. The majority of subjects agreed to be contacted for follow
      up (84.9%) and future research (83.1%). Subject willingness to be contacted for
      future research was associated with greater consenter experience in univariate
      and multivariate analyses. In multivariate analysis, subject willingness to be
      contacted for future research was associated with discordance between subject and
      consenter gender, but not with subject gender, race, or income, or consenter
      gender or race. CONCLUSIONS: Consenter experience and subject-consenter gender
      discordance were associated with greater subject interest in participating in
      future research. The role of consenters in clinical research merits future study
      and should be considered in efforts to increase cancer clinical trial accrual.

PMID- 19401522
TI  - Chemical carcinogenesis models for evaluating molecular-targeted prevention and
      treatment of oral cancer.

PMID- 19401523
TI  - Nonsteroidal anti-inflammatory drug-activated gene-1 expression inhibits urethane
      induced pulmonary tumorigenesis in transgenic mice.
AB  - The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1)
      inhibits gastrointestinal tumorigenesis in NAG-1 transgenic mice (C57/BL6
      background). In the present study, we investigated whether the NAG-1 protein
      would alter urethane-induced pulmonary lesions in NAG-1 transgenic mice on an FVB
      background (NAG-1(Tg+/FVB)). NAG-1(Tg+/FVB) mice had both decreased number and
      size of urethane-induced tumors, compared with control littermates (NAG
      1(Tg+/FVB) = 16 +/- 4 per mouse versus control = 20 +/- 7 per mouse, P < 0.05).
      Urethane-induced pulmonary adenomas and adenocarcinomas were observed in control
      mice; however, only pulmonary adenomas were observed in NAG-1(Tg+/FVB) mice.
      Urethane-induced tumors from control littermates and NAG-1(Tg+/FVB) mice highly
      expressed proteins in the arachidonic acid pathway (cyclooxygenases 1/2,
      prostaglandin E synthase, and prostaglandin E(2) receptor) and highly activated
      several kinases (phospho-Raf-1 and phosphorylated extracellular signal-regulated
      kinase 1/2). However, only urethane-induced p38 mitogen-activated protein kinase
      (MAPK) phosphorylation was decreased in NAG-1(Tg+/FVB) mice. Furthermore,
      significantly increased apoptosis in tumors of NAG-1(Tg+/FVB) mice compared with
      control mice was observed as assessed by caspase-3/7 activity. In addition, fewer
      inflammatory cells were observed in the lung tissue isolated from urethane
      treated NAG-1(Tg+/FVB) mice compared with control mice. These results paralleled
      in vitro assays using human A549 pulmonary carcinoma cells. Less phosphorylated
      p38 MAPK was observed in cells overexpressing NAG-1 compared with control cells.
      Overall, our study revealed for the first time that the NAG-1 protein inhibits
      urethane-induced tumor formation, probably mediated by the p38 MAPK pathway, and
      is a possible new target for lung cancer chemoprevention.

PMID- 19401524
TI  - Methyl-selenium compounds inhibit prostate carcinogenesis in the transgenic
      adenocarcinoma of mouse prostate model with survival benefit.
AB  - Chemoprevention of prostate cancer by second-generation selenium compounds in
      reference to selenomethionine holds strong promise to deal with the disease at
      the root. Here we used the transgenic adenocarcinoma mouse prostate (TRAMP) model
      to establish the efficacy of methylseleninic acid (MSeA) and methylselenocysteine
      (MSeC) against prostate carcinogenesis and to characterize potential mechanisms.
      Eight-week-old male TRAMP mice (C57B/6 background) were given a daily oral dose
      of water, MSeA, or MSeC at 3 mg Se/kg body weight and were euthanized at either
      18 or 26 weeks of age. By 18 weeks of age, the genitourinary tract and
      dorsolateral prostate weights for the MSeA- and MSeC-treated groups were lower
      than for the control (P < 0.01). At 26 weeks, 4 of 10 control mice had
      genitourinary weight >2 g, and only 1 of 10 in each of the Se groups did. The
      efficacy was accompanied by delayed lesion progression, increased apoptosis, and
      decreased proliferation without appreciable changes of T-antigen expression in
      the dorsolateral prostate of Se-treated mice and decreased serum insulin-like
      growth factor I when compared with control mice. In another experiment, giving
      MSeA to TRAMP mice from 10 or 16 weeks of age increased their survival to 50
      weeks of age, and delayed the death due to synaptophysin-positive neuroendocrine
      carcinomas and synaptophysin-negative prostate lesions and seminal vesicle
      hypertrophy. Wild-type mice receiving MSeA from 10 weeks did not exhibit
      decreased body weight or genitourinary weight or increased serum alanine
      aminotransferase compared with the control mice. Therefore, these selenium
      compounds may effectively inhibit this model of prostate cancer carcinogenesis.

PMID- 19401525
TI  - Short-term prophylactic tamoxifen reduces the incidence of antiestrogen
      resistant/estrogen receptor-positive/progesterone receptor-negative mammary
      tumors.
AB  - Although many estrogen receptor-positive (ER+) breast cancers are effectively
      treated with selective estrogen receptor modulators and down-regulators
      (SERM/SERD), some are highly resistant. Resistance is more likely if primary
      cancers are devoid of progesterone receptors (PR-) or have high levels of growth
      factor activity. In this study, a transgenic mouse line that expresses
      transforming growth factor-alpha (NRL-TGFalpha mice) and that develops ER+/PR-
      mammary tumors was used to assess the possible effects of (a) therapeutic
      delivery of the SERM, tamoxifen, or SERD, ICI I82,780 (ICI), on the growth of
      established tumors and (b) short-term prophylactic tamoxifen administration on
      the initial development of new mammary tumors. To determine the therapeutic
      effects of tamoxifen and ICI on the growth of established tumors, mice were
      exposed to 3 weeks of drug treatment. Neither drug influenced tumor growth or
      glandular pathology. To determine if early prophylactic tamoxifen could alter
      tumorigenesis, a 60-day tamoxifen treatment was initiated in 8-week-old mice.
      Compared with placebo-treated mice, tamoxifen reduced tumor incidence by 50% and
      significantly decreased the degree of mammary hyperplasia. Prophylactic tamoxifen
      also significantly extended the life span of tumor-free mice. These data show
      that in this mouse model, established ER+/PR- mammary tumors are resistant to
      SERM/SERD treatment but the development of new mammary tumors can be prevented by
      an early course of tamoxifen. This study validates the utility of NRL-TGFalpha
      mice for (a) identifying candidate biomarkers of efficacious tamoxifen
      chemoprevention and (b) modeling the evolution of tamoxifen resistance.

PMID- 19401527
TI  - Early detection of oral neoplasia: watching with new eyes.

PMID- 19401526
TI  - Glutathione S-transferase polymorphisms and risk of second primary malignancy
      after index squamous cell carcinoma of the head and neck.
AB  - Glutathione S-transferases (GST) detoxify carcinogens in tobacco smoke, which
      plays a major role in development of not only squamous cell carcinoma of the head
      and neck (SCCHN) but also second primary malignancy (SPM) after index SCCHN. We
      hypothesized that GSTM1 null, GSTT1 null, GSTP1 Ile(105)Val, and GSTP1
      Ala(114)Val polymorphisms would individually and, more likely, collectively show
      an association with risk of SPM after index SCCHN. One thousand three hundred
      seventy-six incident SCCHN patients were prospectively recruited between May 1996
      and December 2006, genotyped, and followed for SPM development. One hundred ten
      patients (8%) developed SPM: 43 (39%) second SCCHN, 38 (35%) other tobacco
      associated sites, and 29 (26%) other non-tobacco-associated sites. Patients with
      GSTP1 Ile(105)Val polymorphism had a statistically significant association with
      risk of SPM development (adjusted hazard ratio, 1.7; 95% confidence interval, 1.1
      2.5). However, no statistically significant associations were observed with
      GSTM1, GSTT1, or GSTP1 Ala(114)Val polymorphisms. After combining risk genotypes
      for all four polymorphisms, rates of SPM development with 0 to 1, 2, 3, and 4
      risk genotypes were 6.4%, 8.4%, 10.9%, and 15.1%, respectively, and a stepwise
      increase in SPM risk was observed with increasing number of risk genotypes (P =
      0.004 for trend). Patients with 3 to 4 risk genotypes had a 1.7-fold increased
      risk for SPM compared with patients with 0 to 2 risk genotypes (hazard ratio,
      1.70; 95% confidence interval, 1.2-2.5). This large prospective cohort study
      supports a modestly increased risk of SPM after index SCCHN with GSTP1
      Ile(105)Val polymorphism and an even greater risk of SPM with multiple combined
      GST risk genotypes.

PMID- 19401529
TI  - Constitutive short telomere length of chromosome 17p and 12q but not 11q and 2p
      is associated with an increased risk for esophageal cancer.
AB  - Shortened telomere length may cause chromosomal instability in Barrett's
      esophagus and thus promote tumorigenesis. However, whether short telomere length
      in all chromosomes or just some of them is associated with increased esophageal
      cancer (EC) risk is largely unknown. To address this question, we examined the
      overall and chromosome-specific telomere lengths of 17p, 12q, 2p, and 11q and
      assessed their associations with EC risk. In a case-control study with 94 EC
      cases and 94 matched controls, the overall telomere length and the chromosome
      specific telomere lengths of 17p, 12q, 2p, and 11q in peripheral blood
      lymphocytes were determined by a real-time PCR and a modified single telomere
      length analysis assay, respectively. Multivariate logistic regression analysis
      was used to assess the association between telomere length and EC risk. Compared
      with controls, EC patients had significantly shorter overall telomere lengths (P
      = 0.004) and chromosome-specific telomere lengths of 17p (P = 0.003) and 12q (P =
      0.006) but not of 11q (P = 0.632) and 2p (P = 0.972). Furthermore, the
      multivariate logistic regression analysis showed that the short overall telomere
      length and chromosome-specific telomere lengths of 17p and 12q were associated
      with a dose-dependent increase in EC risk. Our study provides the first
      epidemiologic evidence that short telomere length of 17p and 12q plays an
      important role in esophageal carcinogenesis, suggesting that short telomere
      length of specific chromosomes is associated with the etiology of different
      cancer types.

PMID- 19401528
TI  - A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or
      without alpha tocopherol or observation in subjects at high risk for lung cancer.
AB  - No chemoprevention strategies have been proven effective for lung cancer. We
      evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without alpha
      tocopherol, as a lung cancer chemoprevention agent in a phase II randomized
      controlled clinical trial of adult subjects at high risk for lung cancer as
      defined by the presence of sputum atypia, history of smoking, and airflow
      obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free,
      >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA
      plus alpha tocopherol (13-cis RA/alpha toco) or observation for 12 months.
      Outcome measures are derived from histologic evaluation of bronchial biopsy
      specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome
      measure is treatment "failure" defined as histologic progression (any increase in
      the maximum histologic score) or failure to return for follow-up bronchoscopy.
      Seventy-five subjects were randomized (27/22/26 to observations/13-cis RA/13-cis
      RA/alpha toco); 59 completed the trial; 55 had both baseline and follow-up
      bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of
      48) in the observation and combined (13 cis RA plus 13 cis RA/alpha toco)
      treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97;
      95% confidence interval, 0.36-2.66; P = 0.95). Among subjects with complete
      histology data, maximum histology score in the observation arm increased by 0.37
      units and by 0.03 units in the treated arms (difference adjusted for baseline, 
      0.18; 95% confidence interval, -1.16 to 0.81; P = 0.72). Similar (nonsignificant)
      results were observed for treatment effects on endobronchial proliferation as
      assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced
      nonsignificant changes in bronchial histology, consistent with results in other
      trials. Agents advancing to phase III randomized trials should produce greater
      histologic changes. The addition of alpha tocopherol did not affect toxicity.

PMID- 19401530
TI  - Objective detection and delineation of oral neoplasia using autofluorescence
      imaging.
AB  - Although the oral cavity is easily accessible to inspection, patients with oral
      cancer most often present at a late stage, leading to high morbidity and
      mortality. Autofluorescence imaging has emerged as a promising technology to aid
      clinicians in screening for oral neoplasia and as an aid to resection, but
      current approaches rely on subjective interpretation. We present a new method to
      objectively delineate neoplastic oral mucosa using autofluorescence imaging.
      Autofluorescence images were obtained from 56 patients with oral lesions and 11
      normal volunteers. From these images, 276 measurements from 159 unique regions of
      interest (ROI) sites corresponding to normal and confirmed neoplastic areas were
      identified. Data from ROIs in the first 46 subjects were used to develop a simple
      classification algorithm based on the ratio of red-to-green fluorescence;
      performance of this algorithm was then validated using data from the ROIs in the
      last 21 subjects. This algorithm was applied to patient images to create visual
      disease probability maps across the field of view. Histologic sections of
      resected tissue were used to validate the disease probability maps. The best
      discrimination between neoplastic and nonneoplastic areas was obtained at 405 nm
      excitation; normal tissue could be discriminated from dysplasia and invasive
      cancer with a 95.9% sensitivity and 96.2% specificity in the training set, and
      with a 100% sensitivity and 91.4% specificity in the validation set. Disease
      probability maps qualitatively agreed with both clinical impression and
      histology. Autofluorescence imaging coupled with objective image analysis
      provided a sensitive and noninvasive tool for the detection of oral neoplasia.

PMID- 19401531
TI  - A combination of micronutrients is beneficial in reducing the incidence of
      prostate cancer and increasing survival in the Lady transgenic model.
AB  - We have previously shown that administration of a combination of micronutrients
      (selenium, vitamin E, and lycopene) inhibits prostate cancer (PCa) development in
      the Lady transgenic model. In the present study, we examine timing of initiation
      of micronutrients, and the effect of micronutrient combinations, on PCa
      development in Lady transgenic model. Transgenic males were randomized to either
      a control diet; control diet supplemented with human equivalent doses of vitamin
      E, selenium, and lycopene (E+S+L); or control diet supplemented with vitamin E
      and selenium (E+S). In separate experiments, the combination of E+S+L was
      initiated at varying time points (4, 8, 20, and 36 weeks of age). A combination
      of E+S+L resulted in a significant reduction in PCa and liver metastasis when
      intervention was commenced within 8 weeks of age (P < 0.0001).
      Immunohistochemical analysis revealed a strong correlation between disease-free
      state with up-regulation of the prognostic marker p27(Kip1) (P < 0.0001) and
      decreased expression of proliferating cell nuclear antigen and significantly
      increased apoptotic index (P < 0.0001). On the contrary, a combination of E+S was
      not effectual in preventing PCa, with a high proportion (84.6%) of animals
      developing PCa and a small proportion (11.5%) developing high-grade PIN. Early
      commencement of micronutrients (E+S+L) is beneficial in reducing PCa. Lycopene is
      an essential component of the combination and effective (when used with E+S) for
      PCa prevention. These observations provide support for their chemopreventive
      effect and some clues about their mechanism of action. These key findings will be
      complementary to the outcome from the Selenium and Vitamin E Chemoprevention
      Trial.

PMID- 19401532
TI  - Cancer prevention and treatment with resveratrol: from rodent studies to clinical
      trials.
AB  - Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a dietary polyphenol derived
      from grapes, berries, peanuts, and other plant sources. During the last decade,
      resveratrol has been shown to possess a fascinating spectrum of pharmacologic
      properties. Multiple biochemical and molecular actions seem to contribute to
      resveratrol effects against precancerous or cancer cells. Resveratrol affects all
      three discrete stages of carcinogenesis (initiation, promotion, and progression)
      by modulating signal transduction pathways that control cell division and growth,
      apoptosis, inflammation, angiogenesis, and metastasis. The anticancer property of
      resveratrol has been supported by its ability to inhibit proliferation of a wide
      variety of human tumor cells in vitro. These in vitro data have led to numerous
      preclinical animal studies to evaluate the potential of this drug for cancer
      chemoprevention and chemotherapy. This review provides concise, comprehensive
      data from preclinical in vivo studies in various rodent models of human cancers,
      highlighting the related mechanisms of action. Bioavailability, pharmacokinetic,
      and potential toxicity studies of resveratrol in humans and ongoing
      interventional clinical trials are also presented. The conclusion describes
      directions for future resveratrol research to establish its activity and utility
      as a human cancer preventive and therapeutic drug.

PMID- 19401533
TI  - Tracing the "at-risk" oral mucosa field with autofluorescence: steps toward
      clinical impact.

PMID- 19401535
TI  - John Jacob Abel: the fifth horseman.

PMID- 19401536
TI  - Jean-Pierre Changeux: allostery as neuro-enlightenment.

PMID- 19401534
TI  - Nonsteroidal anti-inflammatory drug use and endometrial cancer risk in the NIH
      AARP Diet and Health Study.
AB  - Chronic inflammation may play an etiologic role in endometrial cancer.
      Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammatory activity by
      inhibiting the proinflammatory cyclooxygenase enzymes and, therefore, may
      decrease cancer risk. However, few studies have examined the association between
      NSAID use and endometrial cancer. We conducted a prospective study among 72,524
      women in the NIH-AARP Diet and Health Study. Women completed a questionnaire in
      1996-1997 on lifestyle and health-related factors, including type and frequency
      of NSAID use within the past year, and were followed through 2003 by linkages to
      cancer registries and vital status databases. During 488,261 person-years of
      follow-up, there were 732 incident endometrial cancers. NSAID use, compared with
      nonuse of NSAIDs, was not significantly associated with endometrial cancer risk
      [relative risk (RR), 0.90; 95% confidence interval (95% CI), 0.74-1.09]. Null
      associations were also observed by type of NSAID use [aspirin only: RR, 0.88; 95%
      CI, 0.70-1.11; nonaspirin NSAID (NA-NSAID) only: RR, 1.01; 95% CI, 0.79-1.29;
      both aspirin and NA-NSAIDs: RR, 0.85; 95% CI, 0.68-1.06]. Generally, results were
      not statistically significant by frequency of use for aspirin or NA-NSAIDs.
      Results did not change when women with a history of heart disease, hypertension,
      or diabetes were excluded to minimize the potential for confounding by
      indication. Overall, our data do not support an association between aspirin or NA
      NSAID use and endometrial cancer risk.

PMID- 19401538
TI  - Anti-HIV-1 therapeutics: from FDA-approved drugs to hypothetical future targets.

PMID- 19401539
TI  - Does targeting the lipophilic milieu provide advantages for an endothelin
      antagonist?

PMID- 19401540
TI  - Antifibrillatory agents and potassium channels in the atria: pore block versus
      channel trafficking.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia. The preferred
      therapy for AF is sustained sinus rhythm control; however, the efficacy of
      currently used antiarrythmic drugs is limited by adverse side effects resulting
      from both a lack of ion channel selectivity and nonspecific ventricular activity.
      The role of the voltage-gated potassium channels in atrial myocyte repolarization
      and the subsequent control of action potential duration renders them attractive
      targets for antiarrhythmic drugs in the treatment of AF. Conventional
      antiarrhythmic drugs generally target the ion permeability of potassium channels.
      This review discusses the limitations of this traditional approach and
      introduces, as a novel paradigm for antiarrhythmic pharmacology, the decrease of
      ion channel cell surface density through the modulation of ion channel
      trafficking pathways.

PMID- 19401541
TI  - Proteases display biased agonism at protease-activated receptors: location
      matters!
AB  - Protease-activated receptors (PARs) are G protein-coupled receptors (GPCRs) that
      transmit cellular responses begun by the actions of extracellular proteases. The
      activation of a PAR occurs by a unique mechanism whereby the extracellular N
      terminal segment of the inactive receptor undergoes proteolytic cleavage,
      resulting in irreversible activation--unlike most GPCRs that are reversibly
      activated. PARs mediate cellular responses to coagulant proteases in various cell
      types localized within the vasculature. Additionally, PARs are expressed in other
      cell types and respond to a plethora of proteases. Recent studies have revealed
      that different proteases elicit distinct responses through the activation of the
      same PAR. This phenomenon appears to involve stabilization of distinct active PAR
      conformations that facilitates selectively coupling to different effectors and is
      localized to caveolae, a subtype of lipid rafts.

PMID- 19401542
TI  - Ninth Biannual Report of the Cochrane Haematological Malignancies Group--focus on
      hematopoietic growth factors.

PMID- 19401543
TI  - Physical activity, weight control, and breast cancer risk and survival: clinical
      trial rationale and design considerations.
AB  - Substantial observational epidemiological evidence exists that physical activity
      and weight control are associated with decreased risk of postmenopausal breast
      cancer. Uncertainty remains regarding several aspects of these associations,
      including the effect of possible confounding factors on these associations. We
      present the rationale and design for two randomized controlled trials that can
      help resolve this uncertainty. In a 5-year prevention trial conducted among women
      at high risk of breast cancer, the primary endpoint would be breast cancer
      incidence. For a comparable survivorship trial, the primary endpoint would be the
      disease-free interval and secondary endpoints would be breast cancer recurrence
      free interval, second primary breast cancer, and total invasive plus in situ
      breast cancer. A set of inclusion and exclusion criteria is proposed for both
      trials. Intervention goals are the same for both trials. Goals for the weight
      control intervention would be, for women whose body mass index (BMI) is greater
      than 25 kg/m(2), to lose 10% of body weight and, for women whose BMI is less than
      or equal to 25 kg/m(2), to avoid weight gain. The goal for the physical activity
      intervention would be to achieve and maintain regular participation in a moderate
      intensity physical activity program for a total of 150-225 minutes over at least
      5 days per week. Sample size calculations are based on alternative assumptions
      about hazard ratio, adherence, follow-up duration, and power and are presented
      for the primary prevention and survivorship trials. Although both studies could
      enhance our understanding of breast cancer etiology and benefit public health,
      practical considerations, including smaller sample size, ease of recruitment, and
      reduced likelihood of early termination, favor the survivorship trial at this
      time.

PMID- 19401544
TI  - Four-gene expression ratio test for survival in patients undergoing surgery for
      mesothelioma.
AB  - BACKGROUND: Malignant pleural mesothelioma has few effective treatments, one
      being cytoreductive surgery. We previously developed a gene ratio test to predict
      outcome of malignant pleural mesothelioma patients undergoing surgery. In this
      study, we investigated the predictive value and technical assay performance of
      this test in patients with malignant pleural mesothelioma. METHODS: Clinical data
      were obtained prospectively from 120 consecutive patients with malignant pleural
      mesothelioma who were scheduled for debulking surgery at one institution.
      Specimens were obtained at surgery or by pleural biopsy examination. Expression
      data for four genes were collected from tumor specimens, and three ratios of gene
      expression (TM4SF1/PKM2, TM4SF1/ARHGDIA, and COBLL1/ARHGDIA) were determined by
      quantitative reverse transcriptase-polymerase chain reaction. Patients were
      assigned to good or poor outcome groups by the gene ratio test. Survival was
      estimated by the Kaplan-Meier method and the log-rank test in univariate
      analyses. A multivariable Cox proportional hazards model was used to control for
      prognostic factors. Technical robustness was determined by using up to 30
      specimens per patient, two biopsy techniques, and two performance sites. All
      statistical tests were two-sided. RESULTS: The test predicted overall survival (P
      < .001) and cancer-specific survival (P = .007) in univariate analysis and
      overall survival in multivariable analysis (hazard ratio for death = 2.09, 95%
      confidence interval [CI] = 1.27 to 3.45, P = .004). The test was reproducible
      within patients and repeatable between two determinations for specimens with
      widely varying tumor cell contents. Repeatability between two determinations was
      88.5% (95% CI = 84.0% to 92.2%) or, when technically unacceptable test values
      were excluded, 91.9% (95% CI = 87.4% to 95.1%). Reproducibility between two
      determinations was 96.1% (95% CI = 86.5% to 99.5%). Combining the gene ratio test
      and other prognostic factors allowed prospective discrimination between patients
      at high risk (median survival = 6.9 months, 95% CI = 2.6 to 8.9 months; 3-year
      survival = 0%) and low risk (median survival = 31.9 months, 95% CI = 21.9 to 41.7
      months; 3-year survival = 42%). CONCLUSION: The gene ratio test for survival of
      patients with malignant pleural mesothelioma has robust predictive value and
      technical assay performance.

PMID- 19401545
TI  - Re: Calcium plus vitamin D supplementation and the risk of breast cancer.

PMID- 19401547
TI  - StatBite: Cause of Death Among Prostate Cancer Patients by Gleason Score.

PMID- 19401548
TI  - Whatever happened to immunotoxins? Research, and hope, are still alive.

PMID- 19401546
TI  - Topoisomerase II alpha and responsiveness of breast cancer to adjuvant
      chemotherapy.
AB  - BACKGROUND: Amplification or deletion of the topoisomerase II alpha (TOP2A) gene
      in breast cancers has been postulated to be more closely associated with
      responsiveness to anthracycline-containing chemotherapy than amplification of the
      human epidermal growth factor receptor type 2 (HER2) gene. METHODS: We studied
      438 tumors from 710 premenopausal women with node-positive breast cancer who
      received cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) or
      cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) as adjuvant chemotherapy
      in the randomized National Cancer Institute of Canada Clinical Trials Group
      Mammary 5 (MA.5) trial. TOP2A alterations and HER2 amplification were quantified
      by fluorescence in situ hybridization. The association of TOP2A and HER2 status
      with recurrence-free survival (RFS) and overall survival (OS) in the two
      treatment groups was analyzed using Kaplan-Meier curves, the log-rank test, and
      Cox proportional hazard models. All statistical tests were two-sided. RESULTS: In
      patients whose tumors showed TOP2A alterations (either amplifications or
      deletions), treatment with CEF was statistically significantly superior to
      treatment with CMF in terms of RFS (adjusted hazard ratio [HR] = 0.35, 95%
      confidence interval [CI] = 0.17 to 0.73, P = .005) and OS (adjusted HR = 0.33,
      95% CI = 0.15 to 0.75, P = .008). In patients without TOP2A amplification or
      deletion, the corresponding adjusted hazard ratios for RFS and OS were 0.90 (95%
      CI = 0.66 to 1.23, P = .49) and 1.09 (95% CI = 0.77 to 1.56, P = .62). Adjusted
      tests of interaction between treatment and TOP2A status were P = .09 for RFS and
      P = .02 for OS. Adjusted tests of interaction between treatment and HER2 status
      were P = .008 for RFS and P = .02 for OS. CONCLUSION: TOP2A gene alterations
      (amplifications or deletions) are associated with an increase in responsiveness
      to anthracycline-containing chemotherapy regimens relative to non-anthracycline
      regimens that is similar to that seen in patients with HER2 amplification.

PMID- 19401551
TI  - Re: Recent trends in breast cancer among younger women in the United States.

PMID- 19401550
TI  - Alterations in the TOP2A and HER2 genes: association with adjuvant anthracycline
      sensitivity in human breast cancers.

PMID- 19401552
TI  - Lung cancer risk in relation to dietary acrylamide intake.
AB  - BACKGROUND: Acrylamide is a probable human carcinogen that is present in several
      heat-treated foods. In epidemiological studies, positive associations between
      dietary acrylamide intake and the risks of endometrial, ovarian, estrogen
      receptor-positive breast, and renal cell cancers have been observed. The
      association between dietary acrylamide intake and lung cancer risk is not known.
      METHODS: We conducted a case-cohort study among 58 279 men and 62 573 women (aged
      55-69 years) in the Netherlands Cohort Study on Diet and Cancer. Intakes of
      acrylamide-containing foods and risk factors for cancer were assessed with a self
      administered questionnaire at baseline in 1986 and combined with acrylamide
      levels in relevant Dutch foods to assess total dietary acrylamide intake. The
      number of person-years at risk was estimated by using a random sample of
      participants from the total cohort that was chosen at baseline (n = 5000).
      Incident lung cancer cases in the total cohort were detected by computerized
      record linkages to the Netherlands Cancer Registry and the Netherlands Pathology
      Registry. Hazard ratios and 95% confidence intervals (CIs) for the risk of lung
      cancer associated with acrylamide intakes were estimated using Cox proportional
      hazards models that controlled for smoking (status, quantity, and duration) and
      other lung cancer risk factors. All statistical tests were two-sided. RESULTS:
      After 13.3 years of follow-up (September 17, 1986 up to January 1, 2000) there
      were 2649 cases of primary, histologically verified lung cancer (International
      Classification of Diseases for Oncology-3 code: C34) when cases with prevalent
      cancer at baseline (other than skin cancer) were excluded. The multivariable
      adjusted hazard ratio of lung cancer for a 10-microg/d increment of acrylamide
      intake was 1.03 (95% CI = 0.96 to 1.11) for men and 0.82 (95% CI = 0.69 to 0.96)
      for women. The hazard ratio of lung cancer for the highest (median intake
      [microg/d]: men = 37.6 and women = 36.8) vs the lowest (median intake [microg/d]:
      men = 10.8 and women = 9.5) quintile of acrylamide intake was 1.03 (95% CI = 0.77
      to 1.39, P(trend) = .85) for men and 0.45 (95% CI = 0.27 to 0.76, P(trend) = .01)
      for women. The inverse association in women was strongest for adenocarcinoma
      (hazard ratio for highest vs lowest tertile of intake = 0.40, 95% CI = 0.21 to
      0.78; P(trend) = .01). CONCLUSIONS: Acrylamide intake was not associated with
      lung cancer risk in men but was inversely associated in women, most strongly for
      adenocarcinoma. This finding suggests that acrylamide is involved in human
      carcinogenesis through pathways other than genotoxicity.

PMID- 19401549
TI  - Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas.
AB  - BACKGROUND: Clusterin expression in various types of human cancers may be higher
      or lower than in normal tissue, and clusterin may promote or inhibit apoptosis,
      cell motility, and inflammation. We investigated the role of clusterin in tumor
      development in mouse models of neuroblastoma. METHODS: We assessed expression of
      microRNAs in the miR-17-92 cluster by real-time reverse transcription-polymerase
      chain reaction in MYCN-transfected SH-SY5Y and SH-EP cells and inhibited
      expression by transfection with microRNA antisense oligonucleotides. Tumor
      development was studied in mice (n = 66) that were heterozygous or homozygous for
      the MYCN transgene and/or for the clusterin gene; these mice were from a cross
      between MYCN-transgenic mice, which develop neuroblastoma, and clusterin-knockout
      mice. Tumor growth and metastasis were studied in immunodeficient mice that were
      injected with human neuroblastoma cells that had enhanced (by clusterin
      transfection, four mice per group) or reduced (by clusterin short hairpin RNA
      [shRNA] transfection, eight mice per group) clusterin expression. All statistical
      tests were two-sided. RESULTS: Clusterin expression increased when expression of
      MYCN-induced miR-17-92 microRNA cluster in SH-SY5Y neuroblastoma cells was
      inhibited by transfection with antisense oligonucleotides compared with scrambled
      oligonucleotides. Statistically significantly more neuroblastoma-bearing MYCN
      transgenic mice were found in groups with zero or one clusterin allele than in
      those with two clusterin alleles (eg, 12 tumor-bearing mice in the zero-allele
      group vs three in the two-allele group, n = 22 mice per group; relative risk for
      neuroblastoma development = 4.85, 95% confidence interval [CI] = 1.69 to 14.00; P
      = .005). Five weeks after injection, fewer clusterin-overexpressing LA-N-5 human
      neuroblastoma cells than control cells were found in mouse liver or bone marrow,
      but statistically significantly more clusterin shRNA-transfected HTLA230 cells
      (3.27%, with decreased clusterin expression) than control-transfected cells
      (1.53%) were found in the bone marrow (difference = 1.74%, 95% CI = 0.24% to
      3.24%, P = .026). CONCLUSIONS: We report, to our knowledge, the first genetic
      evidence that clusterin is a tumor and metastasis suppressor gene.

PMID- 19401553
TI  - Induced abortions in Danish cancer survivors: a population-based cohort study.
AB  - To learn whether female cancer survivors are more likely to terminate a pregnancy
      by choice than other women, the occurrence of induced abortions was determined in
      a population-based cohort of 1688 childhood cancer survivors. Proportion ratios
      (PRs) were estimated from the ratio of the proportion of pregnancies that
      resulted in induced abortions among the survivors (or 16 700 randomly selected
      population control subjects) to the proportion among 2737 sisters of the
      survivors. The proportion of induced abortions among survivors (292 of 1479
      [19.7%]) was marginally higher but not statistically significantly different from
      that among sisters (961 of 5092 [18.9%]; PR = 1.08, 95% confidence interval [CI]
      = 0.96 to 1.22) and similar to that of the population control subjects (5505 of
      27 989 [19.7%]; PR = 1.07, 95% CI = 1.01 to 1.14). Survivors were not more likely
      than sisters and population control subjects to elect a second-trimester abortion
      because of physical and mental conditions or fetal abnormalities.

PMID- 19401554
TI  - The plight of the potato: is dietary acrylamide a risk factor for human cancer?

PMID- 19401555
TI  - Gleason scoring system faces change and debate.

PMID- 19401556
TI  - Change in federal stem cell funding policy spurs interest in field.

PMID- 19401557
TI  - Research probes anticancer mechanisms of Polyphenon E.

PMID- 19401558
TI  - The leukemic stem cell niche: current concepts and therapeutic opportunities.
AB  - The genetic events that contribute to the pathogenesis of acute myeloid leukemia
      are among the best characterized of all human malignancies. However, with notable
      exceptions such as acute promyelocytic leukemia, significant improvements in
      outcome based on these insights have not been forthcoming. Acute myeloid leukemia
      is a paradigm of cancer stem (or leukemia initiating) cells with hierarchy
      analogous to that seen in hematopoiesis. Normal hematopoiesis requires complex
      bidirectional interactions between the bone marrow microenvironment (or niche)
      and hematopoietic stem cells (HSCs). These interactions are critical for the
      maintenance of normal HSC quiescence and perturbations can influence HSC self
      renewal. Leukemia stem cells (LSCs), which also possess limitless self-renewal,
      may hijack these homeostatic mechanisms, take refuge within the sanctuary of the
      niche during chemotherapy, and consequently contribute to eventual disease
      relapse. We will discuss the emerging evidence supporting the importance of the
      bone marrow microenvironment in LSC survival and consider the physiologic
      interactions of HSCs and the niche that inform our understanding of
      microenvironment support of LSCs. Finally, we will discuss approaches for the
      rational development of therapies that target the microenvironment.

PMID- 19401559
TI  - Identification of crassin acetate as a new immunosuppressant triggering heme
      oxygenase-1 expression in dendritic cells.
AB  - By screening 720 natural compounds in a standard 2-way allogeneic mixed leukocyte
      reaction assay, we identified a potent immunosuppressive capacity of crassin
      acetate (CRA), a coral-derived cembrane diterpenoid. CRA efficiently inhibited
      allogeneic mixed leukocyte reaction as well as antigen-specific activation of CD4
      T cells by bone marrow-derived dendritic cells (DCs). With regard to cellular
      targets, CRA suppressed not only mitogen-triggered T-cell activation, but also
      lipopolysaccharide-induced DC maturation, indicating dual functionality.
      Treatment with CRA at nontoxic doses induced heme oxygenase-1 (HO-1) mRNA/protein
      expression and HO-1 enzymatic activity in DCs, suggesting a unique mechanism of
      action. In fact, lipopolysaccharide-induced DC maturation was also inhibited by
      structurally unrelated compounds known to induce HO-1 expression or carbon
      monoxide (CO) release. Allergic contact hypersensitivity response to oxazolone
      and oxazolone-induced Langerhans cell migration from epidermis were both
      prevented almost completely by systemic administration of CRA. Not only do our
      results support the recent concept that HO-1/CO system negatively regulates
      immune responses, they also form both conceptual and technical frameworks for a
      more systematic, large-scale drug discovery effort to identify HO-1/CO-targeted
      immunosuppressants with dual target specificity.

PMID- 19401560
TI  - Serum ferritin as risk factor for sinusoidal obstruction syndrome of the liver in
      patients undergoing hematopoietic stem cell transplantation.
AB  - Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication in
      hematopoietic stem cell transplant (HSCT) recipients. To determine the impact of
      pretransplantation hyperferritinemia on the risk of SOS after HSC
      transplantation, we retrospectively studied 427 HSCT recipients (179 autologous
      and 248 allogeneic). Serum ferritin levels were measured before transplantation.
      Patients with and without a diagnosis of SOS were compared regarding
      demographics; underlying disease; transplant characteristics; receipt of
      imatinib, busulfan, total body irradiation, gemtuzumab, vancomycin, acyclovir, or
      methotrexate; and baseline serum ferritin. Univariate and multivariate (stepwise
      logistic regression) analyses were performed. SOS was diagnosed in 88 patients
      (21%) at a median of 10 days (range, 2-29 days) after transplantation. By
      multivariate analysis, allogeneic HSC transplantation (odds ratio [OR] = 8.25;
      95% confidence interval [95% CI], 3.31-20.57), receipt of imatinib (OR = 2.60;
      95% CI, 1.16-5.84), receipt of busulfan (OR = 2.18; 95% CI, 1.25-3.80), and
      ferritin serum level higher than 1000 ng/dL (OR = 1.78; 95% CI, 1.02-3.08) were
      risk factors for SOS. A ferritin serum level higher than 1000 ng/dL in the
      pretransplantation period is an independent risk factor for SOS. The results
      suggest the need for prospective studies addressing the use of iron chelation in
      the pretransplantation period.

PMID- 19401561
TI  - MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma.
AB  - Detailed genomic studies have shown that cytogenetic abnormalities contribute to
      multiple myeloma (MM) pathogenesis and disease progression. Nevertheless, little
      is known about the characteristics of MM at the epigenetic level and specifically
      how microRNAs regulate MM progression in the context of the bone marrow milieu.
      Therefore, we performed microRNA expression profiling of bone marrow derived
      CD138(+) MM cells versus their normal cellular counterparts and validated data by
      qRT-PCR. We identified a MM-specific microRNA signature characterized by down
      expression of microRNA-15a/-16 and overexpression of microRNA-222/-221/-382/
      181a/-181b (P < .01). We investigated the functional role of microRNA-15a and -16
      and showed that they regulate proliferation and growth of MM cells in vitro and
      in vivo by inhibiting AKT serine/threonine-protein-kinase (AKT3), ribosomal
      protein-S6, MAP-kinases, and NF-kappaB-activator MAP3KIP3. Moreover, miRNA-15a
      and -16 exerted their anti-MM activity even in the context of the bone marrow
      milieu in vitro and in vivo. These data indicate that microRNAs play a pivotal
      role in the biology of MM and represent important targets for novel therapies in
      MM.

PMID- 19401562
TI  - The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76
      kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation.
AB  - The Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons
      (SLP-76) is a cytosolic adaptor protein essential for thymocyte development and T
      cell activation. It contains a sterile-alpha motif (SAM) domain, 3
      phosphotyrosine motifs, a proline-rich region, and a Src homology 2 domain.
      Whereas the other domains have been extensively studied, the role of the SAM
      domain in SLP-76 function is not known. To understand the function of this
      domain, we generated SLP-76 knockin mice with the SAM domain deleted. Analysis of
      these mice showed that thymocyte development was partially blocked at the double
      positive to single-positive transition. Positive and negative thymic selection
      was also impaired. In addition, we analyzed T-cell receptor (TCR)-mediated
      signaling in T cells from these mutant mice. TCR-mediated inositol 1,4,5
      triphosphate production, calcium flux, and extracellular signal-regulated kinase
      activation were decreased, leading to defective interleukin-2 production and
      proliferation. Moreover, despite normal association between Gads and SLP-76, TCR
      mediated formation of SLP-76 microclusters was impaired by the deletion of the
      SAM domain. Altogether, our data demonstrated that the SAM domain is
      indispensable for optimal SLP-76 signaling.

PMID- 19401565
TI  - Will molecular MR imaging play a role in identification and treatment of patients
      with vulnerable atherosclerotic plaques?
AB  - Although the translation of experimental molecular MR imaging agents is highly
      compelling, it is substantially more complex than the translation of radiolabeled
      imaging agents. The prognostic value, safety, and cost-effectiveness of molecular
      MR imaging for the detection of plaque inflammation will need to be demonstrated
      and will require a robust and collaborative effort among basic scientists,
      clinicians, epidemiologists, and industry. The well-conducted and valuable study
      reported by Amirbekian et al in this issue of Radiology adds further momentum to
      this important endeavor.

PMID- 19401563
TI  - SCF induces gamma-globin gene expression by regulating downstream transcription
      factor COUP-TFII.
AB  - Increased fetal hemoglobin expression in adulthood is associated with acute
      stress erythropoiesis. However, the mechanisms underlying gamma-globin induction
      during the rapid expansion of adult erythroid progenitor cells have not been
      fully elucidated. Here, we examined COUP-TFII as a potential repressor of gamma
      globin gene after stem cell factor (SCF) stimulation in cultured human adult
      erythroid progenitor cells. We found that COUP-TFII expression is suppressed by
      SCF through phosphorylation of serine/threonine phosphatase (PP2A) and correlated
      well with fetal hemoglobin induction. Furthermore, down-regulation of COUP-TFII
      expression with small interfering RNA (siRNA) significantly increases the gamma
      globin expression during the erythroid maturation. Moreover, SCF-increased
      expression of NF-YA associated with redox regulator Ref-1 and cellular reducing
      condition enhances the effect of SCF on gamma-globin expression. Activation of
      Erk1/2 plays a critical role in SCF modulation of downstream transcriptional
      factor COUP-TFII, which is involved in the regulation of gamma-globin gene
      induction. Our data show that SCF stimulates Erk1/2 MAPK signaling pathway, which
      regulates the downstream repressor COUP-TFII by inhibiting serine/threonine
      phosphatase 2A activity, and that decreased COUP-TFII expression resulted in
      gamma-globin reactivation in adult erythropoiesis. These observations provide
      insight into the molecular pathways that regulate gamma-globin augmentation
      during stress erythropoiesis.

PMID- 19401566
TI  - Noninvasive carotid artery imaging: caution ahead.

PMID- 19401567
TI  - The radiology report of the future.

PMID- 19401568
TI  - Vessel growth and function: depiction with contrast-enhanced MR imaging.
AB  - Magnetic resonance (MR) imaging is a versatile noninvasive diagnostic tool that
      can be applied to the entire human body to revealing morphologic, functional, and
      metabolic information. The authors review how MR imaging can depict both the
      established and the developing vasculature with techniques involving
      intravenously administered contrast agents. In addition to macrovascular
      morphology and flow, MR imaging is able to exploit microvascular properties,
      including vessel size distribution, hyperpermeability, flow heterogeneity, and
      possibly also upregulation of endothelial biomarkers. For each MR method, the
      basic principles, potential acquisition and interpretation pitfalls, solutions,
      and applications are described. Furthermore, discussion includes current
      shortcomings and the impact of future developments (eg, higher magnetic field
      strength systems, targeted macromolecular contrast agents) on the visualization
      of blood vessel growth and function with contrast-enhanced MR imaging.

PMID- 19401569
TI  - Full-field digital versus screen-film mammography: comparison within the UK
      breast screening program and systematic review of published data.
AB  - PURPOSE: To (a) compare the performance of full-field digital mammography (FFDM),
      using hard-copy image reading, with that of screen-film mammography (SFM) within
      a UK screening program (screening once every 3 years) for women aged 50 years or
      older and (b) conduct a meta-analysis of published findings along with the UK
      data. MATERIALS AND METHODS: The study complied with the UK National Health
      Service Central Office for Research Ethics Committee guidelines; informed patient
      consent was not required, since analysis was carried out retrospectively after
      data anonymization. Between January 2006 and June 2007, a London population-based
      screening center performed 8478 FFDM and 31 720 SFM screening examinations, with
      modality determined by the type of machine available at the screening site.
      Logistic regression was used to assess whether breast cancer detection rates and
      recall rates differed between screening modalities. For the meta-analysis, random
      effects models were used to combine study-specific estimates, if appropriate.
      RESULTS: A total of 263 breast cancers were detected. After adjustment for age,
      ethnicity, area of residence, and type of referral, there was no evidence of
      differences between FFDM and SFM in terms of detection rates (0.68 [95%
      confidence interval {CI}: 0.47, 0.89] vs 0.72 [95% CI: 0.58, 0.85], respectively,
      per 100 screening mammograms; P = .74), recall rates (3.2% [95% CI: 2.8, 3.6] vs
      3.4% [95% CI: 3.1, 3.6]; P = .44), positive predictive value (PPV) of an abnormal
      mammogram, or characteristics of detected tumors. Meta-analysis of data from
      eight studies showed a slightly higher detection rate for FFDM, particularly at
      60 years of age or younger (pooled FFDM-SFM difference: 0.11 [95% CI: 0.04, 0.18]
      per 100 screening mammograms), but no clear modality differences in recall rates
      or PPVs. CONCLUSION: Within a routine screening program, FFDM with hard-copy
      image reading performed as well as SFM in terms of process indicators; the meta
      analysis was consistent with FFDM yielding detection rates at least as high as
      those for SFM.

PMID- 19401570
TI  - Learning curve for coronary CT angiography: what constitutes sufficient training?
AB  - PURPOSE: To prospectively evaluate the effect of experience with coronary
      computed tomographic (CT) angiography on the capability to detect coronary
      stenoses of 50% or more. MATERIALS AND METHODS: The institutional review board
      approved the study protocol. All patients gave consent to undergo CT angiography
      before conventional coronary angiography after being informed of the additional
      radiation dose. They also consented to the use of their data for future research.
      Three radiologists and one cardiologist inexperienced with coronary CT
      angiography attended this institution's cardiac CT unit for a 1-year fellowship.
      Fellows were involved in the acquisition and reading of 12-15 coronary CT
      angiograms per week (about 600 per year). To assess the progression in diagnostic
      performance, fellows (readers) independently read 50 CT angiographic test cases
      in patients who also underwent conventional coronary angiography. Cases were
      repeatedly assigned in random order at baseline and at 4, 8, 26, and 52 weeks.
      The same cases were examined by two experts in consensus. Sensitivity,
      specificity, and diagnostic odds ratios (DORs) were calculated and compared with
      conventional coronary angiography as the reference standard. RESULTS: Respective
      reader ranges for sensitivity, specificity, and DOR were 33%-72%, 70%-94%, and
      3.8-8.1 at baseline; 43%-80%, 71%-88%, and 8.8-15.2 after 6 months; and 66%-75%,
      87%-92%, and 14.7-25.8 after 1 year. For expert physicians, respective results
      were 95%, 93%, and 255.9. Between baseline and 6 months, readers 1-3 showed
      nonsignificantly improved sensitivities, while specificities remained similar.
      Reader 4 showed significantly improved specificity, while sensitivity remained
      similar; all readers nonsignificantly improved DORs. Between baseline and 1 year:
      readers 1 and 2 significantly improved sensitivity but not specificity; reader 4
      significantly improved specificity but not sensitivity; readers 1, 2, and 4
      improved DOR significantly; reader 3 nonsignificantly improved sensitivity,
      specificity, and DOR. CONCLUSION: Increasing experience with coronary CT
      angiography improved the diagnostic performance of inexperienced physicians.
      However, acquiring expertise in coronary CT angiography was slow and may take
      more than 1 year.

PMID- 19401571
TI  - Perianal Crohn disease: evaluation of dynamic contrast-enhanced MR imaging as an
      indicator of disease activity.
AB  - PURPOSE: To prospectively determine clinical value of dynamic contrast material
      enhanced magnetic resonance (MR) imaging in the evaluation of disease activity in
      perianal Crohn disease (CD). MATERIALS AND METHODS: Patients provided written
      informed consent. Study approval was waived by an institutional review board.
      Thirty-three patients with perianal CD underwent pelvic MR imaging; 17 were male
      (mean age, 37.4 years +/- 10.8 [standard deviation]; age range, 18-54 years) and
      16 were female (mean age, 32.0 years +/- 8.3; age range, 16-43 years). Dynamic
      contrast-enhanced MR imaging was performed; time-intensity curves (TICs) were
      obtained. Each pixel was classified as one of six predefined TIC shape types. For
      each MR imaging examination, a region of interest (ROI) was drawn around the
      fistula on the single section corresponding to the most extensive and most
      hyperintense lesion; maximum enhancement (ME), slope of enhancement, and TIC
      shapes were calculated. Absolute and relative numbers of pixels for each curve
      type were calculated in a two-dimensional ROI. These results were compared with
      Perianal Disease Activity Index (PDAI), C-reactive protein (CRP) level, an MR
      imaging-based severity score, and clinical outcome. A Spearman rank correlation
      test was used to calculate correlation coefficients between dynamic contrast
      enhanced MR imaging parameters and reference parameters. A Mann-Whitney U test
      was used to calculate differences in dynamic contrast-enhanced MR imaging
      parameters between predefined groups of patients. RESULTS: Significant
      correlations were found between the absolute amounts of the TIC shape types and
      PDAI and between ROI volume and PDAI. The ratio of quickly enhancing versus
      slowly enhancing pixels correlated with higher MR imaging scores as did the ROI
      volume. The absolute amounts of pixels displaying TIC types 2, 3, 4, and 5
      correlated significantly with MR imaging score. CRP level showed a significant
      correlation with mean ME. Larger numbers of quickly enhancing pixels were
      observed in patients who needed medication changes or developed new abscesses
      during follow-up. CONCLUSION: Dynamic contrast-enhanced MR imaging can help
      determine disease activity in perianal CD and might be helpful in selecting a
      subpopulation of patients who should be monitored more closely for development of
      more extensive disease.

PMID- 19401572
TI  - Hepatic lesions: improved image quality and detection with the periodically
      rotated overlapping parallel lines with enhanced reconstruction technique-
      evaluation of SPIO-enhanced T2-weighted MR images.
AB  - PURPOSE: To evaluate the effectiveness of the periodically rotated overlapping
      parallel lines with enhanced reconstruction (PROPELLER) technique for
      superparamagnetic iron oxide (SPIO)-enhanced T2-weighted magnetic resonance (MR)
      imaging with respiratory compensation with the prospective acquisition correction
      (PACE) technique in the detection of hepatic lesions. MATERIALS AND METHODS: The
      institutional human research committee approved this prospective study, and all
      patients provided written informed consent. Eighty-one patients (mean age, 58
      years) underwent hepatic 1.5-T MR imaging. Fat-saturated T2-weighted turbo spin
      echo images were acquired with the PACE technique and with and without the
      PROPELLER method after administration of SPIO. Images were qualitatively
      evaluated for image artifacts, depiction of liver edge and intrahepatic vessels,
      overall image quality, and presence of lesions. Three radiologists independently
      assessed these characteristics with a five-point confidence scale. Diagnostic
      performance was assessed with receiver operating characteristic (ROC) curve
      analysis. Quantitative analysis was conducted by measuring the liver signal-to
      noise ratio (SNR) and the lesion-to-liver contrast-to-noise ratio (CNR). The
      Wilcoxon signed rank test and two-tailed Student t test were used, and P < .05
      indicated a significant difference. RESULTS: MR imaging with the PROPELLER and
      PACE techniques resulted in significantly improved image quality, higher
      sensitivity, and greater area under the ROC curve for hepatic lesion detection
      than did MR imaging with the PACE technique alone (P < .001). The mean liver SNR
      and the lesion-to-liver CNR were higher with the PROPELLER technique than without
      it (P < .001). CONCLUSION: T2-weighted MR imaging with the PROPELLER and PACE
      technique and SPIO enhancement is a promising method with which to improve the
      detection of hepatic lesions. (c) RSNA, 2009.

PMID- 19401573
TI  - Prostate cancer: detection of lymph node metastases outside the routine surgical
      area with ferumoxtran-10-enhanced MR imaging.
AB  - PURPOSE: To prospectively evaluate the feasibility of magnetic resonance (MR)
      imaging with ferumoxtran-10 in patients with prostate cancer to depict lymph node
      metastases outside the routine pelvic lymph node dissection (PLND) area.
      MATERIALS AND METHODS: The study was approved by the institutional review boards
      at all four hospitals; patients provided written informed consent. Two hundred
      ninety-six consecutive men (mean age, 67 years; range, 47-83 years) with prostate
      cancer and an intermediate-to-high risk for nodal metastases (prostate-specific
      antigen level >10 ng/mL, Gleason score >6, or stage T3 disease) were enrolled. MR
      lymphography of the pelvis was performed 24 hours after intravenous drip infusion
      of ferumoxtran-10. Positive nodes at MR lymphography were indicated to be inside
      or outside the routine dissection area (RDA). On the basis of MR lymphography
      computed tomographic (CT)-guided biopsy, routine PLND, or MR imaging-guided
      minimal extended PLND was performed. RESULTS: MR lymphography findings were
      positive in 58 patients. Of these, 44 had histopathologic confirmation of lymph
      node metastases. In 18 of 44 patients (41%), MR lymphography findings showed
      nodes exclusively outside the RDA, which were confirmed with MR lymphography
      guided extended PLND (n = 13) and CT-guided biopsy (n = 5). In another 18
      patients (41%), positive nodes were located both inside and outside the RDA at MR
      lymphography. In these 18 patients, routine PLND was used to confirm the nodes
      inside the RDA (n = 11); CT-guided biopsy was used to confirm nodes outside the
      RDA (n = 7). In the remaining eight patients, MR lymphography findings showed
      only nodes inside the RDA, which was confirmed with PLND (n = 5) and CT-guided
      biopsy (n = 3). In 14 of the 58 patients (24%), there was no histologic
      confirmation. CONCLUSION: In 41% of patients with prostate cancer, nodal
      metastases outside the area of routine PLND were detected by using MR imaging
      with ferumoxtran-10.

PMID- 19401574
TI  - Gadofosveset-enhanced MR angiography of carotid arteries: does steady-state
      imaging improve accuracy of first-pass imaging? Comparison with selective digital
      subtraction angiography.
AB  - PURPOSE: To evaluate the diagnostic accuracy of gadofosveset-enhanced magnetic
      resonance (MR) angiography in the assessment of carotid artery stenosis, with
      digital subtraction angiography (DSA) as the reference standard, and to determine
      the value of reading first-pass, steady-state, and "combined" (first-pass plus
      steady-state) MR angiograms. MATERIALS AND METHODS: This study was approved by
      the local ethics committee, and all subjects gave written informed consent. MR
      angiography and DSA were performed in 84 patients (56 men, 28 women; age range,
      61-76 years) with carotid artery stenosis at Doppler ultrasonography. Three
      readers reviewed the first-pass, steady-state, and combined MR data sets, and one
      independent observer evaluated the DSA images to assess stenosis degree, plaque
      morphology and ulceration, stenosis length, and tandem lesions. Interobserver
      agreement regarding MR angiographic findings was analyzed by using intraclass
      correlation and Cohen kappa coefficients. Sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV) were calculated by
      using the McNemar test to determine possible significant differences (P < .05).
      RESULTS: Interobserver agreement regarding all MR angiogram readings was
      substantial. For grading stenosis, sensitivity, specificity, PPV, and NPV were,
      respectively, 90%, 92%, 91%, and 91% for first-pass imaging; 95% each for steady
      state imaging; and 96%, 99%, 99%, and 97% for combined imaging. For evaluation of
      plaque morphology, respective values were 84%, 86%, 88%, and 82% for first-pass
      imaging; 98%, 97%, 98%, and 97% for steady-state imaging; and 98%, 100%, 100%,
      and 97% for combined imaging. Differences between the first-pass, steady-state,
      and combined image readings for assessment of stenosis degree and plaque
      morphology were significant (P < .001). CONCLUSION: Gadofosveset-enhanced MR
      angiography is a promising technique for imaging carotid artery stenosis. Steady
      state image reading is superior to first-pass image reading, but the combined
      reading protocol is more accurate.

PMID- 19401575
TI  - Depressive disorders: focally altered cerebral perfusion measured with arterial
      spin-labeling MR imaging.
AB  - PURPOSE: To assess focal cerebral perfusion in patients with refractory
      depressive disorder (RDD), patients with nonrefractory depressive disorder (NDD),
      and healthy control subjects by using arterial spin-labeling (ASL) magnetic
      resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the
      local ethical committee, and written informed consent was obtained from all
      participants. Twenty-four patients with RDD, 37 patients with NDD, and 42 healthy
      control subjects were included. From February 2006 to July 2007, all participants
      were imaged with a 3-T MR system. ASL and echo-planar images were subtracted and
      averaged to give perfusion-weighted images. Voxel-based analysis was performed.
      Region-of-interest analysis was applied to the bilateral hippocampi, thalami, and
      lentiform nuclei. RESULTS: Patients with NDD showed reduced perfusion in the left
      prefrontal cortex versus control subjects and increased perfusion mainly in the
      limbic-striatal areas (P < .05). In contrast, patients with RDD had decreased
      perfusion predominantly in the bilateral frontal and bilateral thalamic regions
      (P < .05). Compared with patients with RDD, patients with NDD showed higher
      perfusion mainly in the limbic-striatal areas (P < .05). In region-of-interest
      analysis, the NDD group showed higher regional cerebral blood flow than both RDD
      and control groups in the left hippocampus (P = .045), right hippocampus (P =
      .001), and right lentiform nucleus (P = .049). CONCLUSION: This study revealed
      alterations of regional perfusion in the brains of patients with RDD that
      differed from those in patients with NDD. These results are consistent with the
      concept that RDD is associated with decreased activity of the bilateral
      prefrontal areas; and NDD, with decreased activity of left frontal areas in
      conjunction with overactivity of the bilateral limbic system.

PMID- 19401576
TI  - Multiple sclerosis: hyperintense dentate nucleus on unenhanced T1-weighted MR
      images is associated with the secondary progressive subtype.
AB  - PURPOSE: To describe the occurrence of abnormal hyperintensity in the dentate
      nucleus on T1-weighted magnetic resonance (MR) images in patients with multiple
      sclerosis (MS) as a neuroradiologic sign of gray matter involvement. Presence of
      the finding was evaluated for association with disability, clinical MS subtype,
      total lesion volume on T1- and T2-weighted MR images (lesion load), and brain
      atrophy. MATERIALS AND METHODS: Written informed consent was waived by the Ethics
      Committee because of the retrospective nature of this single-center Institutional
      Review Board-approved study. MR examinations of 185 patients with MS were
      reviewed, and 119 patients were included for analysis. Two neuroimagers, who were
      blinded to clinical data, assessed the presence of a hyperintense dentate nucleus
      on T1-weighted MR images. The presence of this radiologic alteration was then
      evaluated in relation to MS subtype, clinical disability, T1 and T2 lesion load,
      and whole-brain atrophy measurements. Fisher exact, chi(2), and Mann-Whitney U
      tests were used to evaluate differences in clinical and imaging features between
      patients with and those without a T1 hyperintense dentate nucleus. RESULTS:
      Twenty-three (19.3%) of the 119 patients had a hyperintense dentate nucleus on
      unenhanced T1-weighted MR images. This finding was related to the secondary
      progressive subtype of the disease, a higher score on the Expanded Disability
      Status Scale, a higher brain lesion load, and tissue loss. None of the patients
      with primary progressive MS had a hypterintense dentate nucleus. CONCLUSION:
      Hyperintensity of the dentate nucleus may be present on unenhanced T1-weighted MR
      images of patients with MS and is associated with the secondary progressive
      disease subtype and with increased clinical disability, lesion load, and brain
      atrophy.

PMID- 19401578
TI  - Enhancing transjugular intrahepatic portosystemic shunt puncture by using three
      dimensional path planning based on the back projection of two two-dimensional
      portographs.
AB  - The purpose of this study was to prevent transjugular intrahepatic portosystemic
      shunt (TIPS) puncture failure by using three-dimensional (3D) path planning. This
      study was approved by the institutional review board; informed consent was
      obtained for the TIPS procedure. In four patients, a 3D path was planned from two
      two-dimensional (2D) CO2 portograms obtained at projections of 0 degrees and
      right anterior oblique 30 degrees . This path was overlaid onto the live
      fluoroscopy to guide the puncture image. In three of four patients, the target
      vessel was entered in the first attempt. In one patient with portal vein (PV)
      stenosis, the PV was entered with the third pass. This method has high potential
      to improve safety of the procedure and to reduce intervention time.

PMID- 19401577
TI  - Sickle cell disease: ratio of blood flow velocity of intracranial to extracranial
      cerebral arteries--initial experience.
AB  - PURPOSE: To establish reference values of the ratios of flow velocity in the
      middle cerebral artery (V(MCA)) and the terminal portion of the internal carotid
      artery (V(tICA)) to flow velocity in the extracranial portion of internal carotid
      artery (V(ICA)) in children with sickle cell disease (SCD). MATERIALS AND
      METHODS: Institutional ethics committee approval and parental informed consent
      were obtained for this prospective HIPAA-compliant study. Sixty-eight children
      (38 female; mean age, 7.7 years +/- 3.3; range, 2-14 years) with HbSS genotype,
      without neurologic deficits and no history of stroke, were enrolled. Final study
      population comprised 56 (mean age 8.0 +/- 3.3 years, 26 females) children who
      underwent magnetic resonance (MR) angiography, which excluded intracranial
      arterial narrowing, transcranial color-coded duplex ultrasonography (US), and
      carotid US to determine V(MCA)/V(ICA) and V(tICA)/V(ICA) ratios from angle
      corrected and uncorrected velocities. Tolerance interval estimates were used to
      calculate reference ranges and linear regression was used to quantify
      associations of Doppler parameters with age adjusted for hemoglobin and
      hematocrit. RESULTS: Reference ranges in centimeters per second for mean angle
      corrected V(MCA) on the left and right sides were 62-198 and 69-153; those for
      V(tICA) were 30-196 and 36-175; and those for V(ICA) were 18-116 and 15-95,
      respectively. Reference ranges for mean angle-corrected V(MCA)/V(ICA) ratio on
      the left and right sides were 1.2-4.0 and 0.4-3.4 and those for V(tICA)/V(IC)(A)
      ratio were 0.5-2.9 and 0.5-2.7, respectively. V(MCA), V(tICA), and V(tICA)/V(ICA)
      ratio were not age dependent, contrary to V(ICA) and V(MCA)/V(ICA) ratio, after
      controlling for hematocrit and hemoglobin. CONCLUSION: The study provides
      reference limits for V(MCA), V(tICA), V(ICA), and velocity ratios obtained from
      children with SCD.

PMID- 19401579
TI  - Knee cartilage: efficient and reproducible segmentation on high-spatial
      resolution MR images with the semiautomated graph-cut algorithm method.
AB  - This HIPAA-compliant study was exempt from institutional review board approval
      because the 10 image data sets were deidentified in the Osteoarthritis Initiative
      database, and they were processed and analyzed without any clinical information
      being accessed. The purpose of this study was to prospectively evaluate the
      efficiency and reproducibility of the semiautomated graph-cut method (SA method)
      in the segmentation of knee cartilage and to compare its performance with that of
      the conventional manual delineation segmentation method (M method). Two
      radiologists independently performed segmentation with each method in two
      separate sessions: They performed the M method (M1 and M2 for the first and
      second sessions, respectively) for every third section and the SA method (SA1 and
      SA2 for the first and second sessions, respectively) for every section. The SA
      method was significantly more efficient (mean processing time, 53 minutes vs 156
      minutes for SA1 vs M1 and 53 minutes vs 118 minutes for SA2 vs M2; P < .001) and
      reproducible (mean volume overlap, 94.3% vs 87.8% for the SA method vs the M
      method; P < .001) than the M method.

PMID- 19401580
TI  - Lung morphology in the elderly: comparative CT study of subjects over 75 years
      old versus those under 55 years old.
AB  - PURPOSE: To describe thin-section pulmonary computed tomographic (CT) features in
      asymptomatic elderly individuals. MATERIALS AND METHODS: Institutional review
      board approval was given, and informed consent was obtained. Two study groups
      (older group, over 75 years of age; younger group, under 55 years) were
      prospectively identified from outpatient requests for CT of the abdomen or brain.
      Fifty-six consecutive volunteers (older group: n = 40, 18 men, 22 women; younger
      group: n = 16, eight men, eight women) with no known respiratory disease were
      included. Prone thin-section CT imaging was performed, and two observers
      independently scored images for the presence and extent of CT features (including
      reticular pattern, ground glass opacity, and thin-walled cystic air spaces).
      Group comparisons were made, and logistic regression analysis was used to assess
      relationships between CT findings and age and smoking history. RESULTS: A limited
      predominantly subpleural basal reticular pattern was identified in the majority
      (24 of 40, 60%) of individuals in the older group and was absent (zero of 16) in
      the younger group (P < .001). Cysts were seen in 10 (25%) of the 40 subjects in
      the older group but were seen in none of the subjects in the younger group (P =
      .02). Bronchial dilation and wall thickening were also seen significantly more
      frequently (P < .001) in the older group (24 [60%] and 22 [55%] of 40,
      respectively) than in the younger group (both one [6%] of 16). All findings were
      independent of pack-year smoking history with multiple logistic regression
      analysis. CONCLUSION: Thin-section CT findings usually associated with
      interstitial lung disease are frequently seen in asymptomatic elderly individuals
      and are absent in younger subjects. Therefore, these findings may not necessarily
      represent clinically relevant disease.

PMID- 19401581
TI  - Contrast-enhanced harmonic compound US of the spleen to increase staging accuracy
      in patients with Hodgkin lymphoma: a prospective study.
AB  - PURPOSE: To prospectively compare contrast material-enhanced harmonic compound
      ultrasonography (US), computed tomography (CT), and fluorine 18
      fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting nodular
      infiltration in the spleen of patients with newly diagnosed Hodgkin lymphoma.
      MATERIALS AND METHODS: After institutional review board approval and informed
      consent, 100 consecutive patients with Hodgkin lymphoma during pretreatment
      staging were prospectively investigated for possible spleen involvement by
      comparing harmonic compound US (integrated with intravenous infusion of
      microbubbles in 33 patients) with CT and FDG PET. Findings indicative of
      malignant nodules with the imaging procedures were regarded as lymphoma
      infiltration; in case of discrepancy, response to treatment was regarded as
      evidence of lymphoma. RESULTS: Malignant nodules were detected with CT in 13
      patients, with FDG PET in 13 patients, and with contrast-enhanced harmonic
      compound US in 30 patients. Coincidental findings of malignancy with all three
      imaging techniques occurred in 13 patients; 17 patients had only US-detectable
      malignant nodules, which showed disappearance or relevant decrease after
      chemotherapy. Overall, the spleen had nodular infiltration in 30 patients (13 for
      imaging finding concordance; 17 for typical contrast-enhanced harmonic compound
      US findings and chemotherapy-related nodule size modifications). Thus, both CT
      and FDG PET provided false-negative results in 17 of 30 patients compared with
      contrast-enhanced harmonic compound US, the results of which translated into
      disease upstaging in 13 patients. CONCLUSION: Harmonic compound US with contrast
      enhancement for the characterization of possible nodules provides a higher
      sensitivity than does CT or FDG PET in the detection of splenic involvement by
      Hodgkin lymphoma.

PMID- 19401582
TI  - Endoleak detection with CT angiography in an abdominal aortic aneurysm phantom:
      effect of tube energy, simulated patient size, and physical properties of
      endoleaks.
AB  - PURPOSE: To analyze the detection of endoleaks with low-tube-voltage computed
      tomographic (CT) angiography. MATERIALS AND METHODS: A cylindrical plastic
      phantom mimicking an aortic aneurysm, containing a stent graft and 36 simulated
      endoleaks of various diameters, densities, and distances from the graft, was
      placed into three different water containers corresponding to small, intermediate
      sized, and large patients. CT was performed at 80, 100, and 120 kVp, and the
      volume CT dose index (CTDI(vol)) was noted. Three radiologists independently
      analyzed the CT images for endoleak localization with diagnostic confidence and
      for image quality. Analysis of variance was used to compare results and to find
      parameters that have an effect on endoleak detection. RESULTS: All 6-mm endoleaks
      were correctly identified at all tube energies except for five endoleaks at 80
      kVp in the thick phantom. Observers detected more 4-mm leaks at higher tube
      voltage in the thick phantom (P < .001) and at 100 kVp compared with 80 kVp in
      the intermediate phantom (P = .006). Compared with CTDI(vol) at 120 kVp,
      CTDI(vol) was lower by nearly 50% at 80 kVp in the thin and intermediate phantoms
      and at 100 kVp in the thick phantom. Endoleak diameter, position, phantom
      dimension, and tube voltage all had a significant effect on the number of
      detected leaks (P < .0001). CONCLUSION: This phantom study suggests that reduced
      radiation exposure is achievable with CT angiography at 80 kVp in small and
      intermediate-sized patients and at 100 kVp in large patients, with no increased
      risk of missing significant endoleaks measuring 6 mm or larger.

PMID- 19401584
TI  - Case 145: retained sponge.

PMID- 19401585
TI  - Quantity counts: industrial-academic relationships and disclosures.

PMID- 19401586
TI  - Is nephrogenic systemic fibrosis linked to the introduction of contrast-enhanced
      MR angiography?

PMID- 19401587
TI  - Is the use of intravenous contrast material truly safe in patients with impaired
      renal function?

PMID- 19401588
TI  - Omic empiricism.

PMID- 19401589
TI  - Nontraditional signaling mechanisms of lipoprotein receptors.
AB  - The low-density lipoprotein receptor family consists of a large number of single
      transmembrane proteins that are involved both in endocytosis of extracellular
      ligands and in intracellular signaling processes. New evidence ties these
      receptors to the transactivation of Trk receptors. Thus, this single receptor
      family demonstrates several distinct mechanisms for transducing information
      across the plasma membrane.

PMID- 19401590
TI  - Mechanobiology of the skeleton.
AB  - Mechanical loading of the skeleton is essential for the development, growth, and
      maintenance of strong, weight-bearing bones. Bone strength is plastic and can be
      modulated in adults, as illustrated by the increased bone mass in the playing
      arms of athletes as compared with their nonplaying arms. Our studies have shown
      that mechanical loading improves bone strength by inducing bone formation in
      regions of high strain energy. Therefore, bone tissue has a mechanosensing
      apparatus that directs osteogenesis to where it is most needed to increase bone
      strength. The most likely sensors of mechanical loading are the osteocytes, which
      are visco-elastically coupled to the bone matrix so that their biological
      response increases with loading rate; thus, increasing loading frequency improves
      the responsiveness of bone to loading. The osteocyte-specific protein sclerostin,
      an inhibitor of the Wnt signaling pathway, appears to be one of the mediators of
      the mechanical loading response. Mechanical loading suppresses osteocyte
      sclerostin secretion, which allows Wnt signaling-dependent bone formation to
      occur. Intracellular calcium signaling, adenosine triphosphate signaling, and
      signaling through second messengers, such as prostaglandins and nitric oxide,
      precede sclerostin secretion. Stretch-activated ion channels and focal adhesion
      proteins may play a role in triggering these pathways upstream of sclerostin. In
      particular, focal adhesion kinase and proline-rich tyrosine kinase 2 appear to be
      sensors of mechanical loads in bone cells.

PMID- 19401591
TI  - Galpha(i1) and Galpha(i3) are required for epidermal growth factor-mediated
      activation of the Akt-mTORC1 pathway.
AB  - The precise mechanism whereby epidermal growth factor (EGF) activates the serine
      threonine kinase Akt and the mammalian target of rapamycin (mTOR) complex 1
      (mTORC1) remains elusive. Here, we report that the alpha subunits of the
      heterotrimeric guanine nucleotide-binding proteins (G proteins) Galpha(i1) and
      Galpha(i3) are critical for this activation process. Both Galpha(i1) and
      Galpha(i3) formed complexes with growth factor receptor binding 2 (Grb2)
      associated binding protein 1 (Gab1) and the EGF receptor (EGFR) and were required
      for the phosphorylation of Gab1 and its subsequent interaction with the p85
      subunit of phosphatidylinositol 3-kinase in response to EGF. Loss of Galpha(i1)
      and Galpha(i3) severely impaired the activation of Akt and of p70 S6 kinase and
      4E-BP1, downstream targets of mTORC1, in response to EGF, heparin-binding EGF
      like growth factor, and transforming growth factor alpha, but not insulin,
      insulin-like growth factor, or platelet-derived growth factor. In addition,
      ablation of Galpha(i1) and Galpha(i3) largely inhibited EGF-induced cell growth,
      migration, and survival and the accumulation of cyclin D1. Overall, this study
      suggests that Galpha(i1) and Galpha(i3) lie downstream of EGFR, but upstream of
      Gab1-mediated activation of Akt and mTORC1, thus revealing a role for Galpha(i)
      proteins in mediating EGFR signaling.

PMID- 19401592
TI  - Ligand binding to LRP1 transactivates Trk receptors by a Src family kinase
      dependent pathway.
AB  - Low-density lipoprotein receptor-related protein 1 (LRP1) functions in
      endocytosis and intracellular signaling for a variety of structurally diverse
      ligands. Although LRP1 has been implicated in several aspects of neuronal
      function, molecular mechanisms underlying the activity of neuronal LRP1 remain
      unclear. Here, we describe a signaling pathway whereby LRP1 transactivates Trk
      receptors. Binding of tissue-type plasminogen activator or alpha(2)-macroglobulin
      (alpha(2)M) to LRP1 resulted in Src family kinase (SFK) activation and SFK
      dependent Trk receptor transactivation in PC12 cells and neurons. Trk receptor
      transactivation was necessary for activation of Akt and extracellular signal
      regulated kinase and for neurite outgrowth downstream of LRP1. Injection of the
      LRP1-binding domain of alpha(2)M into rat dorsal root ganglia induced Trk
      receptor phosphorylation, which was blocked by receptor-associated protein, an
      antagonist of ligand binding to LRP1. Trk receptor transactivation provides a
      mechanism by which diverse LRP1 ligands may show neurotrophic activity.

PMID- 19401593
TI  - Neurotransmitters drive combinatorial multistate postsynaptic density networks.
AB  - The mammalian postsynaptic density (PSD) comprises a complex collection of
      approximately 1100 proteins. Despite extensive knowledge of individual proteins,
      the overall organization of the PSD is poorly understood. Here, we define maps of
      molecular circuitry within the PSD based on phosphorylation of postsynaptic
      proteins. Activation of a single neurotransmitter receptor, the N-methyl-D
      aspartate receptor (NMDAR), changed the phosphorylation status of 127 proteins.
      Stimulation of ionotropic and metabotropic glutamate receptors and dopamine
      receptors activated overlapping networks with distinct combinatorial
      phosphorylation signatures. Using peptide array technology, we identified
      specific phosphorylation motifs and switching mechanisms responsible for the
      integration of neurotransmitter receptor pathways and their coordination of
      multiple substrates in these networks. These combinatorial networks confer high
      information-processing capacity and functional diversity on synapses, and their
      elucidation may provide new insights into disease mechanisms and new
      opportunities for drug discovery.

PMID- 19401595
TI  - A melding of the minds: when primatology meets personality and social psychology.
AB  - Social and personality psychology and behavioral primatology both enjoy long
      histories of research aimed at uncovering the proximate and ultimate determinants
      of primate-human and nonhuman-social behavior. Although they share research
      themes, methodologies, and theories, and although their studied species are
      closely related, there is currently very little interaction between the fields.
      This separation means that researchers in these disciplines miss out on
      opportunities to advance understanding by combining insights from both fields.
      Social and personality psychologists also miss the opportunity for a phylogenetic
      analysis. The time has come to integrate perspectives on primate social
      psychology. Here, the authors provide a historical background and document the
      main similarities and differences in approaches. Next, they present some examples
      of research programs that may benefit from an integrated primate perspective.
      Finally, the authors propose a framework for developing a social psychology
      inclusive of all primates. Such a melding of minds promises to greatly benefit
      those who undertake the challenge.

PMID- 19401594
TI  - Signaling by gasotransmitters.
AB  - Nitric oxide is well established as a major signaling molecule. Evidence is
      accumulating that carbon monoxide and hydrogen sulfide also are physiologic
      mediators in the cardiovascular, immune, and nervous systems. This Review focuses
      on mechanisms whereby they signal by binding to metal centers in metalloproteins,
      such as in guanylyl cyclase, or modifying sulfhydryl groups in protein targets.

PMID- 19401596
TI  - Imaging of integrin alpha(v)beta(3) expression in patients with malignant glioma
      by [18F] Galacto-RGD positron emission tomography.
AB  - Inhibitors targeting the integrin alpha(v)beta(3) are promising new agents
      currently tested in clinical trials for supplemental therapy of glioblastoma
      multiforme (GBM). The aim of our study was to evaluate (18)F-labeled glycosylated
      Arg-Gly-Asp peptide ([(18)F]Galacto-RGD) PET for noninvasive imaging of
      alpha(v)beta(3) expression in patients with GBM, suggesting eligibility for this
      kind of additional treatment. Patients with suspected or recurrent GBM were
      examined with [(18)F]Galacto-RGD PET. Standardized uptake values (SUVs) of tumor
      hotspots, galea, and blood pool were derived by region-of-interest analysis.
      [(18)F]Galacto-RGD PET images were fused with cranial MR images for image-guided
      surgery. Tumor samples taken from areas with intense tracer accumulation in the
      [(18)F]Galacto-RGD PET images and were analyzed histologically and
      immunohistochemically for alpha(v)beta(3) integrin expression. While normal brain
      tissue did not show significant tracer accumulation (mean SUV, 0.09 +/- 0.04),
      GBMs demonstrated significant but heterogeneous tracer uptake, with a maximum in
      the highly proliferating and infiltrating areas of tumors (mean SUV, 1.6 +/-
      0.5). Immunohistochemical staining was prominent in tumor microvessels as well as
      glial tumor cells. In areas of highly proliferating glial tumor cells, tracer
      uptake (SUVs) in the [(18)F]Galacto-RGD PET images correlated with
      immunohistochemical alpha(v)beta(3) integrin expression of corresponding tumor
      samples. These data suggest that [(18)F] Galacto-RGD PET successfully identifies
      alpha(v)beta(3) expression in patients with GBM and might be a promising tool for
      planning and monitoring individualized cancer therapies targeting this integrin.

PMID- 19401597
TI  - Surfome analysis as a fast track to vaccine discovery: identification of a novel
      protective antigen for Group B Streptococcus hypervirulent strain COH1.
AB  - Safe recombinant vaccines, based on a small number of antigenic proteins, are
      emerging as the most attractive, cost-effective solution against infectious
      diseases. In the present work, we confirmed previous data from our laboratory
      showing that whole viable bacterial cell treatment with proteases followed by the
      identification of released peptides by mass spectrometry is the method of choice
      for the rapid and reliable identification of vaccine candidates in Gram-positive
      bacteria. When applied to the Group B Streptococcus COH1 strain, 43 surface
      associated proteins were identified, including all the protective antigens
      described in the literature as well as a new protective antigen, the cell wall
      anchored protein SAN_1485 belonging to the serine-rich repeat protein family.
      This strategy overcomes the difficulties so far encountered in the identification
      of novel vaccine candidates and speeds up the entire vaccine discovery process by
      reducing the number of recombinant proteins to be tested in the animal model.

PMID- 19401598
TI  - Regulation of fibroblast mitochondrial 27-hydroxycholesterol production by active
      plasma membrane cholesterol.
AB  - Side chain oxysterols are cholesterol derivatives thought to signal the abundance
      of cell cholesterol to homeostatic effector proteins. Here, we investigated how
      plasma membrane (PM) cholesterol might regulate 27-hydroxycholesterol (HC)
      biosynthesis in cultured fibroblasts. We showed that PM cholesterol was a major
      substrate for 27-HC production. Biosynthesis commenced within minutes of loading
      depleted cells with cholesterol, concurrent with the rapid inactivation of
      hydroxy-3-methylglutaryl CoA reductase (HMGR). 27-HC production rose
      approximately 30-fold in normal and Niemann-Pick C1 fibroblasts when PM
      cholesterol was increased by approximately 60%. 27-HC production was also
      stimulated by 1-octanol, which displaces PM cholesterol from its phospholipid
      complexes and thereby increases its activity (escape tendency) and elevates its
      intracellular abundance. Conversely, lysophosphatidylserine and U18666A inhibited
      27-HC biosynthesis and the inactivation of HMGR, presumably by reducing the
      activity of PM cholesterol and, therefore, its circulation to mitochondria. We
      conclude that, in this in vitro system, excess (active) PM cholesterol rapidly
      reaches mitochondria where, as the rate-limiting substrate, it stimulates 27-HC
      biosynthesis. The oxysterol product then promotes the rapid degradation of HMGR,
      along with other homeostatic effects. The regulation of 27-HC production by the
      active excess of PM cholesterol can thus provide a feedback mechanism in the
      homeostasis of PM cholesterol.

PMID- 19401600
TI  - Excessive heart rate increase during mild mental stress in preparation for
      exercise predicts sudden death in the general population.
AB  - AIMS: The aim of this study involves the early identification, among apparently
      healthy individuals, of those at high risk for sudden cardiac death. We tested
      the hypothesis that individuals who respond to mild mental stress in preparation
      for exercise test with the largest heart rate increases might be at highest risk.
      METHODS AND RESULTS: Data from 7746 civil servants participating in the Paris
      Prospective Study I, followed-up for 23 years, allowed to compare heart rate
      changes between rest and mild mental stress (preparation prior to an exercise
      test) between subjects who suffered sudden cardiac death (n = 81), non-sudden (n
      = 129) coronary death, or death from any cause (n = 1306). The mean heart rate
      increase during mild mental stress was 8.9 +/- 10.8 b.p.m. Risk of sudden cardiac
      death increased progressively with heart rate increase during mental stress and
      the relative risk of the third vs. the first tertile was 2.09 (95% confidence
      interval, 1.13-3.86) after adjustment for confounders. This relationship was not
      observed for non-sudden coronary death. CONCLUSION: An important heart rate
      increase produced by a mild mental stress predicts long-term risk for sudden
      cardiac death. Heart rate changes before an exercise test may provide a simple
      tool for risk stratification.

PMID- 19401599
TI  - Microwave-assisted sample preparation for rapid and sensitive analysis of H.
      pylori lipid A applicable to a single colony.
AB  - The lipid A of Gram-negative bacteria plays a major role in the pathogenesis of
      bacterial infections. Lipid A diversity is observed both in the number and length
      of fatty-acid side chains and in the presence of terminal phosphate residues and
      associated modifications. In this report, we describe a new sample preparation
      method based on microwave-assisted enzymatic digestion and detergent-free mild
      hydrolysis, in conjunction with a MALDI-time-of-flight (TOF)/TOF analysis, to
      determine the structures of lipid A from Helicobacter pylori. The total time for
      sample preparation and mass spectrometric analysis is within 2 h and applicable
      to profiling the lipid A structures from dried bacterial cells on as little as 1
      microg. The reliability of the technique was further demonstrated through the
      analysis of the lipid A from bacterial cells of different H. pylori strains. The
      phosphorylation and acylation patterns of lipid A could be elucidated using
      material from a single colony. Furthermore, we found unusual heptaacyl lipid A
      species present in H. pylori mutant that have not been previously reported,
      although the abundance was relatively low. The present study provides the first
      characterization of the lipid A component from a single bacterial colony sample
      by mass spectrometry.

PMID- 19401601
TI  - Intimate partner violence: the role of the relationship between perpetrators and
      children who witness violence.
AB  - The issue of the father-child relationship has been greatly ignored in the
      domestic violence research literature. This study investigated whether intimate
      partner violence (IPV) perpetrated by biological fathers resulted in higher
      levels of posttraumatic stress symptoms and behavior problems than violence
      perpetrated by nonbiological fathers and whether children who witnessed violence
      perpetrated by multiple father figures had increased levels of posttraumatic
      stress disorder and behavioral symptoms. Eighty mothers who experienced domestic
      incidents completed the Child Behavior Checklist (CBCL) and the University of
      California at Los Angeles Posttraumatic Stress Disorder Reaction Index (PTSD-RI)
      for their children aged 2 to 18. Children with multiple violent father figures
      had significantly more symptoms on the CBCL than children in the other two
      research groups while controlling for maternal symptoms and trauma history. There
      were no significant differences between the biological and nonbiological father
      groups or among the three groups on the PTSD-RI.

PMID- 19401602
TI  - Personal and perceived peer attitudes supporting sexual aggression as predictors
      of male college students' willingness to intervene against sexual aggression.
AB  - Male college students ( N = 395) completed anonymous surveys to report personal
      attitudes supporting sexual aggression and estimated the attitudes of their
      peers. Participants also indicated their willingness to intervene against a peer
      if they witnessed sexual aggression. Although both personal and peer attitudes
      were correlated with willingness to intervene, in regression analyses only
      perceived peer attitudes emerged as a significant predictor of willingness to
      intervene. Results suggest that personal attitudes supporting sexual aggression
      are not as relevant to men's willingness to intervene against sexual aggression
      as are perceived peer norms regarding sexual aggression. Findings are relevant to
      sexual assault prevention education with men, suggesting that attempts to
      encourage bystander intervention may be best presented in the context of
      challenging perceived norms.

PMID- 19401604
TI  - Basic science summary.
AB  - The 16th Conference on Retroviruses and Opportunistic Infections featured a
      strong and balanced program that showcased exciting research into cellular
      restrictions that defend the cell against viral infection as well as cellular
      cofactors that regulate central steps in viral replication. Immunopathogenesis
      presentations continued to reveal some surprises such as evidence for
      pathogenicity in natural simian immunodeficiency virus infection. The
      identification of novel cellular restrictions and cellular cofactors of viral
      replication indicate the possibility of numerous opportunities for the
      development of novel therapeutic agents for the treatment of HIV and AIDS.

PMID- 19401605
TI  - HIV Vaccine Development.
AB  - Several interesting new vaccine-related studies were presented at the 16th
      Conference on Retroviruses and Opportunistic Infections this year. Transmitted
      viruses appear to be derived from cell-free virus rather than cell-associated
      virus, at least in men who have sex with men. Follow-up studies from the Step
      (HIV Vaccine Trials Network 502) trial indicated that if individuals mounted
      certain vaccine-induced responses, they may control viral replication after
      infection. Finally, adeno-associated-virus-derived neutralizing antibodies
      completely protected macaques from infection, suggesting novel mechanisms of
      viral control.

PMID- 19401603
TI  - Effect of Pin1 or microtubule binding on dephosphorylation of FTDP-17 mutant Tau.
AB  - Neurodegenerative tauopathies, including Alzheimer disease, are characterized by
      abnormal hyperphosphorylation of the microtubule-associated protein Tau. One
      group of tauopathies, known as frontotemporal dementia with parkinsonism linked
      to chromosome 17 (FTDP-17), is directly associated with mutations of the gene
      tau. However, it is unknown why mutant Tau is highly phosphorylated in the
      patient brain. In contrast to in vivo high phosphorylation, FTDP-17 Tau is
      phosphorylated less than wild-type Tau in vitro. Because phosphorylation is a
      balance between kinase and phosphatase activities, we investigated
      dephosphorylation of mutant Tau proteins, P301L and R406W. Tau phosphorylated by
      Cdk5-p25 was dephosphorylated by protein phosphatases in rat brain extracts.
      Compared with wild-type Tau, R406W was dephosphorylated faster and P301L slower.
      The two-dimensional phosphopeptide map analysis suggested that faster
      dephosphorylation of R406W was due to a lack of phosphorylation at Ser-404, which
      is relatively resistant to dephosphorylation. We studied the effect of the
      peptidyl-prolyl isomerase Pin1 or microtubule binding on dephosphorylation of
      wild-type Tau, P301L, and R406W in vitro. Pin1 catalyzes the cis/trans
      isomerization of phospho-Ser/Thr-Pro sequences in a subset of proteins.
      Dephosphorylation of wild-type Tau was reduced in brain extracts of Pin1-knockout
      mice, and this reduction was not observed with P301L and R406W. On the other
      hand, binding to microtubules almost abolished dephosphorylation of wild-type and
      mutant Tau proteins. These results demonstrate that mutation of Tau and its
      association with microtubules may change the conformation of Tau, thereby
      suppressing dephosphorylation and potentially contributing to the etiology of
      tauopathies.

PMID- 19401606
TI  - The epidemiology of new HIV infections and interventions to limit HIV
      transmission.
AB  - After the disappointing news reported at the 2008 (15th) Conference on
      Retroviruses and Opportunistic Infections regarding HIV vaccines, microbicides,
      and herpes virus suppression trials, the 16th conference this year brought
      welcome advances in the HIV prevention field. In particular, substantial progress
      is being made in approaches to preexposure prophylaxis in preclinical and
      clinical trials, and an efficacy trial of a vaginal microbicide appeared to
      provide women in Africa and the United States with modest protection against HIV
      acquisition. This review covers presentations on the epidemiology of HIV
      infection in specific global populations, strategies to improve the uptake of HIV
      testing, lessons from previous negative prevention trials, and progress in the
      development of new biomedical interventions.

PMID- 19401608
TI  - Complications of HIV disease and antiretroviral therapy.
AB  - Continued progress in the diagnosis, management, and prevention of complications
      of HIV disease and antiretroviral therapy were reported at the 16th Conference on
      Retroviruses and Opportunistic Infections. This year's conference brought new
      data on the optimal management of antiretroviral therapy in the presence of
      different opportunistic infections and included a number of important studies on
      pathogenesis and epidemiology of long-term complications. Major areas in which
      new information was presented are highlighted in this article.

PMID- 19401607
TI  - Neurologic complications of HIV disease and their treatment.
AB  - Substantial work on the peripheral and central nervous system complications of
      HIV was presented at the 16th Conference on Retroviruses and Opportunistic
      Infections. Six studies of more than 4500 volunteers identified that distal
      sensory polyneuropathy remains common, ranging from 19% to 66%, with variation
      based on disease stage, type of antiretroviral therapy, age, and height. Eight
      studies of more than 2500 volunteers identified that neurocognitive disorders are
      also common, ranging from 25% to 69%, with variation based on stage of disease,
      antiretroviral use, diabetes mellitus, and coinfection with hepatitis viruses.
      Therapy-focused studies identified that resistance testing of cerebrospinal fluid
      (CSF)-derived HIV may improve management of people with HIV-associated neurologic
      complications, that poorly penetrating antiretroviral therapy is associated with
      persistent low-level HIV RNA in CSF, and that efavirenz concentrations in CSF are
      low but in the therapeutic range in most individuals. Neuroimaging reports
      identified that people living with HIV had abnormal findings on magnetic
      resonance imaging (gray matter atrophy, abnormal white matter), magnetic
      resonance spectroscopy (lower neuronal metabolites), and blood-oxygen-level
      dependent functional magnetic resonance imaging (lower cerebral blood flow).
      Other important findings on the basic neuroscience of HIV and diagnosis and
      management of neurologic opportunistic infections are discussed.

PMID- 19401609
TI  - Advances in antiretroviral therapy.
AB  - The 16th Conference on Retroviruses and Opportunistic Infections maintained its
      tradition of being recognized as the preeminent forum for detailing the state-of
      the-art of antiretroviral therapy. Abundant new and updated information was
      presented on investigational drugs, approaches to the management of treatment
      naive and -experienced patients, the use of drugs for prevention of mother-to
      child HIV-1 transmission, and antiretroviral drug resistance. Of particular note
      were the continued advances in antiretroviral treatment and research emanating
      from resource-limited settings and the presentation of the results of 2 much
      anticipated, phase III trials of interleukin-2, ESPRIT (Evaluation of
      Subcutaneous Proleukin in a Randomized International Trial) and SILCAAT
      (Subcutaneous, Recombinant Human Interleukin-2 in HIV-Infected Patients With Low
      CD4+ Counts Receiving Active Antiretroviral Therapy).

PMID- 19401610
TI  - Investigating the molecular basis for the virulence of Escherichia coli K5 by
      nuclear magnetic resonance analysis of the capsule polysaccharide.
AB  - The capsular polysaccharide of Escherichia coli K5 has been hypothesised to
      promote virulence through its molecular mimicry of host heparan sulphate. To test
      this hypothesis, we have produced pure oligosaccharides from K5 capsular
      polysaccharide and investigated their conformational properties with ultra-high
      field nuclear magnetic resonance (NMR) (900 MHz). Ultra-high-field affords a
      significant resolution enhancement over previous studies and allowed a full
      atomic assignment of the K5 hexasaccharide for the first time. All carbohydrate
      rings adopt a (4)C(1) conformation, the amide sidechains have a trans orientation
      and the hydroxymethyl group is freely exposed to bulk solvent. Initial models of
      the glycosidic linkage conformation based upon simple interpretation of NOE cross
      peaks suggests that the beta1-->4 linkage adopts a 3D geometry of phi
      approximately 60 degrees , psi approximately 0 degrees and the alpha1-->4 linkage
      prefers phi approximately -30 degrees , psi approximately -30 degrees (phi and
      psi being defined by dihedral angles involving linkage protons). In this
      conformation the overall molecular geometries of K5 polysaccharide, heparan
      sulphate and even fully-sulphated heparin are remarkably similar. These results
      substantiate the hypothesis that the K5 capsular polysaccharide confers virulence
      to E. coli K5 by being a 3D molecular mimetic of host heparan sulphate, helping
      it to evade detection by the mammalian immune system.

PMID- 19401611
TI  - Minimizing misdiagnosis: psychometric criteria for possible or probable memory
      impairment.
AB  - BACKGROUND/AIMS: Memory impairment can be easily misdiagnosed in older adults
      because obtaining some low scores is common. The objective of the present study
      is to present new psychometric criteria for determining 'possible' and 'probable'
      memory impairment. METHODS: We propose criteria based on an analysis of
      performance from 450 healthy older adults (55-87 years old) on 3 measures from
      the WMS-III: Logical Memory, Word List, and Visual Reproduction. These measures
      yield 8 age-adjusted scores for learning, recall, and recognition. The proposed
      criteria for memory impairment are based on the prevalence of low scores when
      simultaneously examining all 8 scores and are stratified by current intelligence,
      estimated premorbid intelligence, and education. The criteria are subsequently
      validated on 100 healthy older adults and 34 patients with 'possible' or
      'probable' Alzheimer's Disease (AD). RESULTS: Tables with cutoffs and false
      positive rates are presented for clinical use. In the validation cohort there
      were no misclassifications in AD patients. CONCLUSION: This study presents steps
      in the development of proposed psychometric criteria that, in conjunction with
      clinical judgment, could minimize the misdiagnosis of memory impairment. It is
      important to reduce misdiagnosis in order to (a) optimize patient care, (b)
      provide an accurate foundation for identifying biological and neurological
      markers, and (c) successfully develop disease-modifying treatments. Further
      validation in a sample of older adults with lesser degrees of cognitive
      impairment is needed.

PMID- 19401612
TI  - Heat-shock protein 70-overexpressing gastric epithelial cells are resistant to
      indomethacin-induced apoptosis.
AB  - BACKGROUND/AIMS: Protecting intestinal mucosa from nonsteroidal anti-inflammatory
      drugs is still an unsolved problem. It has been revealed that apoptosis in
      epithelial cells as a result of mitochondrial injury is an important pathogenesis
      in indomethacin-induced gastric mucosal injury. In this study, we revealed the
      effect of overexpressed heat-shock protein 70 (HSP70) in indomethacin-induced
      apoptosis and oxidative stress. METHODS: HSP70-overexpressing rat gastric mucosal
      cells (7018-RGM-1 cells) and control cells (pBK-CMV-12 cells) were used and
      treated with 0-500 microM of indomethacin for 24 h. Cell viability and cytotoxity
      were measured by a WST-8 assay and a lactate dehydrogenase release assay,
      respectively. Apoptosis was observed by fluorescence microscopy staining with
      Hoechst 33342 and propidium iodide. The expression of Bcl-2 family proteins,
      activation of caspase-3, and 4-hydroxy-2-nonenal (4-HNE)-modified proteins were
      assessed by Western blot analysis. RESULTS: Indomethacin caused apoptosis of
      gastric epithelial cells. The 7018-RGM-1 cells survived significantly after
      indomethacin treatment compared to the control cells. The increase in pro
      apoptotic Bad proteins, the decrease in anti-apoptotic Bcl-2 proteins, and
      caspase activation were all suppressed in the 7018-RGM-1 cells. A lower level of
      indomethacin-induced 4-HNE-modification was detected in the 7018-RGM-1 cells than
      in the control cells. CONCLUSION: Overexpressed HSP70 may potentiate resistance
      to apoptosis and oxidative stress in indomethacin-induced gastric epithelial cell
      injury.

PMID- 19401613
TI  - The effects of Helicobacter pylori eradication on body mass index and dyspeptic
      symptoms.
AB  - BACKGROUND AND AIM: The relationship between Helicobacter pylori infection and
      body mass index (BMI) and dyspeptic symptoms is controversial. We investigated
      the changes in BMI and dyspeptic symptoms after H. pylori eradication among
      stages of atrophic gastritis classified according to the serum pepsinogen (PG)
      I/II ratio. METHODS: One hundred and sixty-three H. pylori-positive patients
      underwent eradication therapy for H. pylori. Serum PG I and II concentrations
      were measured before treatment, and the PG I/II ratio was classified into three
      groups: PG I/II ratio <2.0, PG I/II ratio >or=2.0 and <4.0, and PG I/II ratio
      >or=4.0 were considered to be low, middle, and high, respectively. Their BMI and
      abdominal symptoms were checked before, 1 and 5 years after treatment, and these
      changes were investigated among the three groups. RESULTS: The mean BMI changes 1
      year after treatment in the low PG I/II ratio group were significantly higher
      than those in other groups. Most abdominal symptoms in the high PG I/II ratio
      group were most severe before eradication but improved significantly after
      eradication. CONCLUSIONS: The effects of H. pylori eradication on BMI and
      dyspeptic symptoms may be different according to the serum PG I/II ratio before
      eradication.

PMID- 19401614
TI  - Gonadotropin-releasing hormone agonist reduces aromatase cytochrome P450 and
      cyclooxygenase-2 in ovarian endometrioma and eutopic endometrium of patients with
      endometriosis.
AB  - AIMS: To investigate whether the GnRH agonist may reduce aromatase P450 and COX-2
      in the eutopic endometrium of patients with endometriosis and ovarian
      endometrioma. MATERIALS AND METHODS: Endometrial specimens and ovarian
      endometrioma were obtained from 15 women with endometriosis undergoing
      laparoscopic surgery. The stromal cells of the eutopic endometrium and ovarian
      endometroma were cultured in the presence of the GnRH agonist (leuprolide acetate
      0, 1, 5 and 10 microM) for 24 h. To investigate the effects of the GnRH agonist
      on the eutopic endometrium in vivo, biopsy samples of the endometrium (n = 5)
      among the patients who underwent laparoscopy were obtained after GnRH agonist
      therapy. The protein production of aromatase cytochrome P450 and COX-2 was
      examined by Western blot. RESULTS: Proteins of aromatase P450 and COX-2 were
      reduced in the eutopic endometrium of patients with endometriosis treated with
      the GnRH agonist for 3 months. The stromal cells in the culture of endometrial
      explants and ovarian endometrioma which were treated with the GnRH agonist
      reduced the aromatase P450 and COX-2. CONCLUSION: The GnRH agonist reduced
      aromatase P450 and COX-2 by direct action on the eutopic endometrium of patients
      with endometriosis and ovarian endometrioma.

PMID- 19401615
TI  - Effects of E2 and E1 glycosylation on specific membrane fusion in rubella virus
      strain JR23.
AB  - OBJECTIVES: To explore the effects of glycosylation in glycoprotein on membrane
      fusion in rubella virus strain JR23. METHODS: The N-linked glycosylation sites in
      glycoproteins were mutated individually or in combination. Total expression and
      cell surface expression efficiencies of mutant proteins were assayed with Western
      blot and FACS. The fusion functions were assayed with Giemsa staining and
      reporter gene method. Binding activity of mutant proteins was detected with
      hemadsorption assays. RESULTS: We observed that total expression levels of all
      the mutant proteins in cells were unchanged, but the cell surface expression
      efficiencies of all the mutant proteins except E2 S131V were lower than wild-type
      protein. When effects of reduced cell surface expression were eliminated, mutant
      proteins N53G, S73I, S131V and T78A had lower fusion activities than wild-type
      protein, and binding abilities of E2 S73I and E1 T78A decreased slightly. But in
      all the combined mutants, no cell fusion was detected, and only a minor
      hemadsorption was observed in N53G-S131V, N53G-T78A and N53G-T211A. CONCLUSIONS:
      Glycosylation of glycoproteins were involved in cell surface expression
      synergistically. Glycosylation on E2 N53, N71, N129 and E1 N76 altered the
      specific membrane fusion, whereas no effects were detected on E1 N177 and N209
      individually.

PMID- 19401616
TI  - Viral load, antibody titers and recombinant open reading frame 2 protein-induced
      TH1/TH2 cytokines and cellular immune responses in self-limiting and fulminant
      hepatitis e.
AB  - OBJECTIVES: Hepatitis E virus (HEV) is the predominant cause of water-borne
      epidemics, sporadic acute viral hepatitis (AVH) in adults and fulminant hepatic
      failure (FHF) among pregnant women and other adults in India. This preliminary
      study was designed to examine the association of viral load and certain host
      immune responses with uneventful recovery or progression to FHF. METHODS: Viral
      load, anti-HEV antibody titers, rORF2p-induced Th1/Th2 cytokines levels and
      cellular immune responses were assessed in 47 patients with self-limiting
      hepatitis E and 14 FHF-E cases. The controls included 16 anti-HEV-IgM and IgG
      negative healthy individuals. RESULTS: In AVH category, the viral load was 2.4 x
      10(4) +/- 1.92 x 10(4) copies/ml while except for one, all FHF patients were
      negative for HEV RNA; anti-HEV-IgM and IgG titers were higher in the FHF group.
      Lymphocyte proliferative response to rORF2p was comparable in both groups. As
      compared to AVH, significantly higher levels of both Th1 (IFN-gamma, IL-2 and TNF
      alpha) and Th2 (IL-10) cytokines were recorded in FHF patients. Analysis of
      sequential samples differentiated FHF recovered and fatal patients with respect
      to IFN-gamma and IL-12. CONCLUSION: The results document increased Th1/Th2
      responses and anti-HEV titers in FHF patients that warrant in-depth immunological
      studies.

PMID- 19401617
TI  - Rapid detection of porcine reproductive and respiratory syndrome virus by reverse
      transcription loop-mediated isothermal amplification.
AB  - The fragment of the membrane protein M gene with high conservation and
      specificity of porcine reproductive and respiratory syndrome virus (PRRSV) was
      chosen to be the target region, according to which six special primers were
      designed successfully. Reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) was applied to detect the PRRSV by incubation at 65
      degrees for only 45 min with the ladder-like pattern of bands from 182 bp on the
      agarose gel, and the product specificity was confirmed by RsaI. The result of RT
      LAMP could also be visualized directly with the naked eye by adding the
      intercalating dye Picogreen. The RT-LAMP was identified to detect only the PRRSV
      in all viruses tested, which demonstrated the high specificity. By using various
      sample dilutions as templates, the sensitivity of RT-LAMP was found to be 100
      fold higher than that of RT-PCR and could be comparable to the fluorescence
      quantitative RT-PCR. A comparison was obtained by the RT-LAMP and PCR assays
      using 20 clinical samples. Finally, a rapid, convenient and reliable PRRSV
      detection system was developed using the RT-LAMP.

PMID- 19401619
TI  - Key opinion leaders and paediatric antidepressant overprescribing.

PMID- 19401618
TI  - Mechanisms of M3 muscarinic receptor regulation by wash-resistant xanomeline
      binding.
AB  - BACKGROUND/AIMS: Xanomeline has been shown to bind in a unique manner at M1 and
      M3 muscarinic receptors, with interactions at both the orthosteric site and an
      allosteric site. We have previously shown that brief exposure of Chinese hamster
      ovary cells that express the M3 receptor to xanomeline followed by removal of
      free agonist results in a delayed decrease in radioligand binding and receptor
      response to agonists. In the current study, we were interested in determining the
      mechanisms of this effect. METHODS: Cells were treated with carbachol,
      pilocarpine or xanomeline for 1 h followed by washing and either used immediately
      or after waiting for 23 h. Control groups included cells that were not exposed to
      agonists and cells that were treated with agonists for 24 h. Radioligand binding
      and functional assays were conducted to determine the effects of agonist
      treatments. RESULTS: The above treatment protocol with xanomeline resulted in
      similar effects of the binding of [(3)H]NMS and [(3)H]QNB. When receptor function
      is blocked using a variety of methods, the long-term effects of xanomeline
      binding were absent. CONCLUSION: Our data indicate that xanomeline wash-resistant
      binding at the receptor allosteric site leads to receptor downregulation and that
      receptor activation is necessary for these effects.

PMID- 19401620
TI  - Fifty years with the Hamilton scales for anxiety and depression. A tribute to Max
      Hamilton.
AB  - From the moment Max Hamilton started his psychiatric education, he considered
      psychometrics to be a scientific discipline on a par with biochemistry or
      pharmacology in clinical research. His clinimetric skills were in operation in
      the 1950s when randomised clinical trials were established as the method for the
      evaluation of the clinical effects of psychotropic drugs. Inspired by Eysenck,
      Hamilton took the long route around factor analysis in order to qualify his
      scales for anxiety (HAM-A) and depression (HAM-D) as scientific tools. From the
      moment when, 50 years ago, Hamilton published his first placebo-controlled trial
      with an experimental anti-anxiety drug, he realized the dialectic problem in
      using the total score on HAM-A as a sufficient statistic for the measurement of
      outcome. This dialectic problem has been investigated for more than 50 years with
      different types of factor analyses without success. Using modern psychometric
      methods, the solution to this problem is a simple matter of reallocating the
      Hamilton scale items according to the scientific hypothesis under examination.
      Hamilton's original intention, to measure the global burden of the symptoms
      experienced by the patients with affective disorders, is in agreement with the
      DSM-IV and ICD-10 classification systems. Scale reliability and obtainment of
      valid information from patients and their relatives were the most important
      clinimetric innovations to be developed by Hamilton. Max Hamilton therefore
      belongs to the very exclusive family of eminent physicians celebrated by this
      journal with a tribute.

PMID- 19401621
TI  - Quality of life measurement in antidepressant trials. Is there an added value?
AB  - BACKGROUND: Quality of life (QoL) measurement in medicine has gone a long way. It
      has gained popularity as a more humanitarian outcome measurement. In this paper,
      a review is given of its historical backgrounds with a special focus on the use
      of QoL assessment in psychiatry. Different theoretical concepts are discussed. A
      closer look is taken at the use of QoL measurements in antidepressant trials.
      METHODS: An analysis was performed on the use of QoL measurement in recent
      antidepressant trials of duloxetine and escitalopram. RESULTS: QoL measurement
      was found to have abandoned its initial purposes, and to have been used without
      any theoretical framework. CONCLUSIONS: Although frequently used in
      antidepressant trials, the analysis and reporting of results is virtually non
      existent. It remains unclear if QoL measurement, as currently used, gives any
      information that is not already captured by more formal depression rating scales.
      The question then remains whether QoL measurement in antidepressant trials has
      any added value and, if so, whether this is just a story of missed opportunities.

PMID- 19401622
TI  - The decline of pharmaceutical psychiatry and the increasing role of psychological
      medicine.
AB  - The increasing influence of the pharmaceutical industry on psychiatric research
      and practice is leading to an intellectual and clinical crisis. A narrow concept
      of science attempts to apply oversimplified neurobiological models to the
      understanding and treatment of mental disorders, and relegates psychiatrists to a
      marginal role. This paper reviews some emerging trends of renewal that may be
      subsumed under the rubric of psychological medicine: use of a multidisciplinary
      approach, emphasis on psychotherapeutic strategies leading to self-management,
      reliance on repeated assessments, integration of different treatment modalities
      and independence from the pharmaceutical industry. The concept of psychological
      medicine, defined as the clinical application of the psychosomatic approach, may
      provide room for innovative paths in psychiatric research and treatment.

PMID- 19401623
TI  - Conflicts of interest and disclosure in the American Psychiatric Association's
      Clinical Practice Guidelines.
AB  - BACKGROUND: Clinical practice guidelines (CPG) are developed, endorsed, and
      disseminated through professional medical organizations such as the American
      Psychiatric Association (APA) as the standard of care for health care providers.
      Because of their influence, it is critical that CPG are based on objective data,
      unprejudiced by stakeholder groups, and that any financial associations between
      authors of CPG and the pharmaceutical industry are made transparent. The present
      study examined the degree and type of financial ties to the pharmaceutical
      industry held by authors of 3 major CPG. METHODS: By using multimodal screening
      techniques, we investigated the financial relationships to the pharmaceutical
      companies of 20 work group members who authored the guidelines for the treatment
      of schizophrenia, bipolar disorder, and major depressive disorder. RESULTS:
      Eighteen CPG authors (90%) had at least 1 financial tie to the pharmaceutical
      industry. All of the CPG authors who had industry relationships had financial
      relationships with companies whose products were specifically considered or
      included in the guideline they authored. The leading categories of financial
      interest held by CPG authors were research funding (77.7%), consultancies
      (72.2%), members of corporate boards (44.4%), and collaborators in industry
      funded studies (44.4%). CONCLUSIONS: Ninety percent of the authors of 3 major CPG
      in psychiatry had financial ties to companies that manufacture drugs which were
      explicitly or implicitly identified in the guidelines as recommended therapies
      for the respective mental illnesses. None of the financial associations of the
      authors were disclosed in the CPG.

PMID- 19401624
TI  - Functional relaxation and guided imagery as complementary therapy in asthma: a
      randomized controlled clinical trial.
AB  - BACKGROUND: Asthma is a frequently disabling and almost invariably distressing
      disease that has a high overall prevalence. Although relaxation techniques and
      hypnotherapeutic interventions have proven their effectiveness in numerous
      trials, relaxation therapies are still not recommended in treatment guidelines
      due to a lack of methodological quality in many of the trials. Therefore, this
      study aims to investigate the efficacy of the brief relaxation technique of
      functional relaxation (FR) and guided imagery (GI) in adult asthmatics in a
      randomized controlled trial. METHODS: 64 patients with extrinsic bronchial asthma
      were treated over a 4-week period and assessed at baseline, after treatment and
      after 4 months, for follow-up. 16 patients completed FR, 14 GI, 15 both FR and GI
      (FR/GI) and 13 received a placebo relaxation technique as the control
      intervention (CI). The forced expiratory volume in the first second (FEV(1)) as
      well as the specific airway resistance (sR(aw)) were employed as primary outcome
      measures. RESULTS: Participation in FR, GI and FR/GI led to increases in FEV(1)
      (% predicted) of 7.6 +/- 13.2, 3.3 +/- 9.8, and 8.3 +/- 21.0, respectively, as
      compared to -1.8 +/- 11.1 in the CI group at the end of the therapy. After follow
      up, the increases in FEV(1) were 6.9 +/- 10.3 in the FR group, 4.4 +/- 7.3 in the
      GI and 4.5 +/- 8.1 in the FR/GI, compared to -2.8 +/- 9.2 in the CI. Improvements
      in sR(aw) (% predicted) were in keeping with the changes in FEV(1) in all groups.
      CONCLUSIONS: Our study confirms a positive effect of FR on respiratory parameters
      and suggests a clinically relevant long-term benefit from FR as a
      nonpharmacological and complementary therapy treatment option.

PMID- 19401625
TI  - Responses to diuretic treatment in gene-targeted mice lacking serum- and
      glucocorticoid-inducible kinase 1.
AB  - BACKGROUND/AIMS: Serum- and glucocorticoid-inducible kinase 1 (SGK1) stimulates
      the epithelial sodium channel (ENaC), renal outer medullary K(+) channel 1,
      Na(+)/K(+)-ATPase and presumably the Na(+)-Cl(-) cotransporter (NCC). SGK1
      deficient mice (sgk(-/-)) show a compensated salt-losing phenotype with secondary
      hyperaldosteronism. The present experiments explored the role of SGK1 in the
      response to diuretics. METHODS: sgk1(-/-) mice and their wild-type littermates
      (sgk1(+/+)) were treated with the ENaC blocker triamterene (200 mg/l), the Na(+)
      K(+)-2Cl(-) cotransport inhibitor furosemide (125 mg/l), the NCC blocker
      hydrochlorothiazide (400 mg/l) and the mineralocorticoid receptor blocker
      canrenoate (800 mg/l) for 8 days. Renal SGK1 expression was studied using
      quantitative RT-PCR and immunofluorescence. RESULTS: Diuretic treatment increased
      SGK1 mRNA and protein expression in the kidney of wild-type sgk1(+/+) mice. The
      responses to furosemide, hydrochlorothiazide or canrenoate were not different
      between sgk1(+/+) and sgk1(-/-) mice, and were accompanied by moderate increases
      in plasma aldosterone and urea concentrations. However, treatment with
      triamterene in sgk1(-/-) mice (but not in sgk1(+/+) mice) led to severe,
      eventually lethal, body weight loss as well as increases in plasma aldosterone,
      urea and K(+) concentrations. CONCLUSIONS: SGK1 is required for diuretic
      tolerance to triamterene. The observations confirm the impaired kaliuretic
      potency of sgk1(-/-) mice and point to a role of SGK1 in renal Na(+) reabsorption
      by mechanisms other than ENaC.

PMID- 19401626
TI  - Expression of Mcl-1 splicing variants in clear-cell renal cancer and their
      correlation with histopathological parameters and prognosis.
AB  - BACKGROUND/AIMS: Altered expression of the Bcl-2 family member Mcl-1 has been
      linked to the progression and outcome of various malignancies, but its expression
      and potential prognostic value has yet not been investigated in clear-cell renal
      cell carcinomas (ccRCC). METHODS: In this study, dual-colour real-time RT-PCR was
      used to quantify the expression of Mcl-1 splicing variants in malignant and
      paired normal renal tissue samples, obtained from 93 ccRCC patients (median
      follow-up: 45 months) undergoing radical nephrectomy. RESULTS: Over-expression of
      the anti-apoptotic Mcl-1L variant in ccRCC occurred in nearly 60% of the paired
      samples (p = 0.004). Decreased expression, however, was related to poor tumour
      differentiation (p = 0.013) and independently predicted a higher risk for relapse
      (hazard rate 3.99; 95% CI 1.32-12.04; p = 0.014). Kaplan-Meier analyses revealed
      down-regulation of Mcl-1L in ccRCC to be associated with a markedly shortened
      recurrence-free and disease-specific survival, particularly in patients with
      locally advanced (p < 0.001 and p = 0.003) and poorly differentiated tumours (p =
      0.004 and p = 0.011). CONCLUSION: These findings suggest Mcl-1L to provide a
      molecular parameter for outcome prediction in ccRCC patients, down-regulation
      indicating exceptionally aggressive tumour phenotypes.

PMID- 19401627
TI  - Reasons for dropout in infertility treatment.
AB  - BACKGROUND: The objective of this study was to explore the reasons why couples
      discontinue fertility treatment. METHODS: A retrospective exploratory study was
      performed at the Leuven University Fertility Centre, a university hospital-based
      fertility center. Women who discontinued treatment between September 2000 and
      December 2001 were contacted in 2004-2005 by telephone for a standardized
      interview which covered 9 dropout reasons. For each reason, its importance on the
      decision to stop treatment was measured on an 11-point Likert scale. RESULTS: On
      average, psychological burden (x = 5.96) had the highest impact on the decision
      to stop treatment followed by physical burden (x = 4.48) and female age (x =
      3.64). Perceived lack of staff expertise (x = 1.84), negative impact on social
      contacts (x = 2.12) and financial burden (x = 2.16) had the lowest impact on the
      decision to stop treatment. Longer duration of infertility was significantly
      positively correlated with a higher rating of physical burden as a reason to
      discontinue treatment (r = 0.48; p < 0.05). DISCUSSION: On average, psychological
      burden appears to be most frequently named as the number one reason to
      discontinue infertility treatment, whereas financial burden had the lowest
      impact. Longer duration of infertility is associated with more externalizing
      reasons to discontinue treatment.

PMID- 19401629
TI  - Prevalence of occult hepatitis B virus infection in a general adult population in
      Korea.
AB  - OBJECTIVES: We investigated the prevalence of hepatitis B virus (HBV) markers and
      occult HBV infection in a general adult population in Korea. METHODS: HBsAg, anti
      HBs and anti-HBc were analyzed on 1,091 samples of routine medical check-up
      examinees by chemiluminescence immunoassay. Nucleic acid amplification test (NAT)
      was performed on 1,047 HBsAg-negative samples by multiplex real-time polymerase
      chain reaction (PCR) kit for simultaneous detection of HBV, hepatitis C virus,
      and human immunodeficiency virus (Cobas Taqscreen MPX) in pools of six and
      reactive pools were resolved to individual samples, and further discriminated by
      PCR-based assay for HBV (Cobas Ampliscreen HBV). RESULTS: The prevalences of
      HBsAg, anti-HBc, and anti-HBs were 4.0, 39.3, and 75.4%, respectively. The
      prevalence of anti-HBc significantly decreased with decreasing age (p< 0.001).
      Occult HBV infection was found in 7 (0.7%) of 1,047 HBsAg-negative subjects, and
      5 of them were anti-HBc-negative. Sequencing of HBV S gene in 3 cases revealed
      one wild-type and two mutant strains (W74S, F85Y; T63I, W74S, T131N
      substitutions). CONCLUSIONS: This study helps to understand the current status of
      hepatitis B infection and the prevalence of occult HBV infection in a general
      adult population in Korea.

PMID- 19401630
TI  - Molecular analysis of human influenza virus in Tehran, Iran.
AB  - BACKGROUND: To date there are no reports of molecular and phylogenetic analyses
      of human influenza virus in Tehran, Iran. OBJECTIVES: We isolated and
      characterized circulating influenza viruses in a sample of patients in Tehran.
      METHODS: Nasal and pharyngeal swabs were collected from 57 individuals who were
      suspected of having influenza between October 2005 and January 2007. These
      samples were cultured and subsequently genotyped by RT-PCR and sequencing
      analyses. RESULTS: Twelve of 57 samples (21%) were positive for human influenza
      virus. Out of the 12 positive samples, 7 were A/H3N2 (58%), 3 were A/H1N1 (25%)
      and 2 were B subtypes (17%). The phylogenetic analysis of the hemagglutinin gene
      showed that the H1N1 isolates were close to the A/New Caledonia/20/99 and the
      H3N2 isolates were close to the A/Panama/2007/99 and A/Moscow/10/99 vaccine
      strains. CONCLUSION: In a sample of clinical patients in Tehran, Iran, the
      predominant subtype of human influenza virus was determined to be A/H3N2,
      followed by A/H1N1 and B. In addition, phylogenetic analysis on H1 showed some
      genetic drifts from vaccine strains, but the phylogeny of H3 demonstrated that
      these isolates were from the previous vaccine strains.

PMID- 19401631
TI  - In vitro inhibitory effects of disodium cromoglycate on ionic transports involved
      in sickle cell dehydration.
AB  - BACKGROUND: The antiallergic and antiasthmatic drug disodium cromoglycate (DSCG)
      has also demonstrated an activity against sickle cell disease, but the mechanism
      of this action still remains unknown. METHODS: Na(+) and K(+) fluxes were studied
      in red cells obtained from 9 patients affected with sickle cell disease in the
      absence or in the presence of 1 mM of DSCG and deoxygenated under an N(2) flow
      during up to 24 h. RESULTS: A significant inhibiting effect of DSCG on the
      intracellular K(+) exit and the Na(+) entry was observed. CONCLUSION: These
      results demonstrate that DSCG partially inhibits the abnormal K(+) loss which is
      implicated in the dehydration of the sickle cell and the stimulation of sickling.

PMID- 19401628
TI  - Host genetics, steatosis and insulin resistance among African Americans and
      Caucasian Americans with hepatitis C virus genotype-1 infection.
AB  - Hepatic steatosis is the accumulation of fat in liver cells. Insulin resistance
      (IR) occurs when normal amounts of insulin do not stimulate insulin activity in
      cells. Both conditions have been described in hepatitis C virus (HCV) infection
      and are thought to be biologically related. This study examined the association
      of genetic variants with steatosis and IR among 167 African Americans and 184
      Caucasian Americans with HCV genotype-1. Steatosis was defined as at least 5% of
      fat in cells on liver biopsy. IR was quantified as a score greater than 2 from
      the Homeostasis Model Assessment, version 2.2 (HOMA2-IR). Associations were
      investigated by estimating odds ratios separately by race. Statistically
      significant associations (p < 0.05) were observed for variants in interleukin-10
      (IL10), leptin receptor (LEPR), interleukin-6 (IL6) and transforming growth
      factor beta-1 (TGF-beta1) for both outcomes. Some significant interactions were
      observed between IL10,LEPR and TGF-beta1 polymorphisms and HOMA2-IR scores when
      examining steatosis. The interaction of HOMA2-IR and IL10 was consistent in both
      races whereas for LEPR and TGF-beta1 the interactions were statistically
      significant in only one of the racial groups.These results could imply that some
      IL10,LEPR and TGF-beta1 polymorphisms may modify an association between steatosis
      and IR.

PMID- 19401632
TI  - A subtest of the MMSE as a valid test of episodic memory? Comparison with the
      Free and Cued Reminding Test.
AB  - BACKGROUND/AIMS: Episodic memory impairment is known to be the core of
      Alzheimer's disease (AD) dementia syndrome and one of the earliest domains to
      decline. However, episodic memory tests are long and expensive. METHODS: In a
      sample of the French Three-City Study (n = 1,516), we aimed at validating a
      subtest of the Mini-Mental State Examination (MMSE) specifically measuring
      episodic memory. We focused on the correlation between 7 MMSE subscores and 4
      scores of the Free and Cued Selective Reminding Test (FCSRT) evaluating episodic
      memory. We performed linear regressions and principal component analyses to
      identify which MMSE subscores were better correlated with the FCSRT scores.
      Thereafter, we conducted validation analyses on the whole sample (n = 9,077).
      RESULTS: We found that subscores for orientation to time and the 3-word recall
      task were well correlated with FCSRT scores. The summation of these 2 subscores
      was more strongly associated with dementia and AD than the FCSRT scores and the
      total MMSE score. CONCLUSION: Orientation to time and the 3-word recall task
      might provide a good measure of episodic memory. Making the evaluation of
      episodic memory faster and cheaper, this finding can be of direct interest for
      practitioners and epidemiologists.

PMID- 19401659
TI  - Comparison of the effect of propofol and N-acetyl cysteine in preventing
      ischaemia-reperfusion injury.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to compare the effects of
      propofol and N-acetyl cysteine (NAC) on tourniquet-induced ischaemia-reperfusion
      injury by determining malonyldialdehyde, ischaemia-modified albumin, lactate,
      blood gas and haemodynamic levels in arthroscopic knee surgery. METHODS: Sixty
      ASA I or II patients were randomized into three groups. Intrathecal anaesthesia
      was administered using 0.5% heavy bupivacaine in all patients. In group P,
      propofol was administered in a 0.2 mg kg(-1) bolus, followed by infusion at a
      rate of 2 mg kg(-1) h(-1); in group NAC, NAC was administered as an infusion at a
      rate of 5 mg kg(-1) h(-1), and, in group C (the control group), an equal volume
      of isotonic saline was administered to patients until 30 min after reperfusion.
      Blood samplings were obtained immediately before intrathecal anaesthesia (t1), 1
      min before tourniquet release (t2), 5 min after tourniquet release (t3) and 30
      min after tourniquet release (t4). RESULTS: Plasma malonyldialdehyde, ischaemia
      modified albumin and lactate levels increased significantly in group C at t3 and
      t4 compared with the baseline values. Plasma concentrations of malonyldialdehyde,
      ischaemia-modified albumin and lactate in groups P and NAC were significantly
      lower than those in group C at t3 and t4. In blood gas analyses, pH, HCO3 and
      base excess were found to be significantly lower at t3 and t4 compared with t1
      and t2 in group C. Comparisons between groups P and NAC revealed no significant
      differences. CONCLUSION: Small-dose infusions of both propofol and NAC appear to
      provide similar protection against ischaemia-reperfusion injury in arthroscopic
      knee surgery.

PMID- 19401660
TI  - Perioperative assessment of coagulation in paediatric neurosurgical patients
      using thromboelastography.
AB  - BACKGROUND AND OBJECTIVE: Primary brain tumours may be associated with
      coagulation disorders, which can pose intraoperative and postoperative management
      difficulties. Thromboelastography is a useful technique for evaluating
      coagulability. In this study, we evaluated the perioperative coagulation profile
      using both standard laboratory work and thromboelastography in paediatric
      patients undergoing craniotomy for primary brain tumours. METHODS: Forty
      paediatric patients were enrolled in the study. All patients received standard
      anaesthesia. Blood was analysed for both standard laboratory analysis and
      thromboelastography at three points for each patient: preoperatively,
      intraoperatively and postoperatively. Postoperative patients were divided into
      two groups according to the occurrence or nonoccurrence of postoperative
      haematomas: nonhaematoma group and haematoma group. The standard blood analysis
      and thromboelastography values for both groups were compared. RESULTS:
      Perioperative standard blood analysis was within normal limits for all patients,
      with no significant difference between both groups. In the nonhaematoma group,
      thromboelastography values were indicative of a hypercoagulable state that
      started intraoperatively and continued into the first postoperative day. In the
      haematoma group, thromboelastography values were indicative of a hypocoagulable
      state that was evident in the preoperative thromboelastography values and
      continued into the intraoperative as well as the postoperative period.
      CONCLUSION: Thromboelastography may be useful in the perioperative assessment and
      monitoring of coagulation in paediatric neurosurgical patients and helps in
      identifying patients at increased risk of bleeding or thromboembolic events.

PMID- 19401661
TI  - Dexamethasone for postoperative nausea and vomiting prophylaxis: effect on
      glycaemia in obese patients with impaired glucose tolerance.
AB  - BACKGROUND AND OBJECTIVE: Dexamethasone given to prevent postoperative nausea and
      vomiting may produce significant hyperglycaemia in the perioperative period. The
      effect of dexamethasone on patients with impaired glucose tolerance is unknown.
      METHODS: Thirty obese patients with impaired glucose tolerance undergoing
      laparoscopic Roux-en-Y gastric bypass surgery were studied in a double-blind
      fashion. Patients were randomly distributed into two groups: the dexamethasone
      group (n = 15) received dexamethasone 8 mg intravenously after induction of
      anaesthesia; the control group (n = 15) received isotonic saline. Fingerprick
      capillary blood glucose concentrations were measured at baseline and every 2 h
      during the first 12 h after the start of surgery. RESULTS: In both groups, all
      blood glucose concentrations measured after the beginning of surgery were higher
      than baseline values. However, the dexamethasone group showed higher glucose
      concentrations than the control group from the 6th to the 12th hour of the study.
      In addition, the maximum blood glucose value in the dexamethasone group (10.4 +/-
      1.6 mmol l(-1)) was higher than in the controls (8.8 +/- 1.7 mmol l(-1)) (P <
      0.05). CONCLUSION: Dexamethasone, 8 mg, intravenously administered at the
      beginning of laparoscopic bariatric surgery in patients with impaired glucose
      tolerance is associated with significantly increased postoperative blood glucose
      concentrations.

PMID- 19401662
TI  - Effects of changes in blood pressure and airway pressures on parameters of fluid
      responsiveness.
AB  - BACKGROUND AND OBJECTIVE: Systolic pressure variation (SPV) and stroke volume
      variation (SVV) are clinical indicators of fluid responsiveness. However, several
      factors may influence these parameters and thereby limit their usefulness. In
      this clinical study, we analysed SPV and SVV in comparison with static preload
      parameters during an increase in arterial blood pressure (BP) and airway
      pressure. METHODS: We studied 16 postoperative cardiac surgical and mechanically
      ventilated patients who, for clinical reasons, underwent haemodynamic monitoring
      by transpulmonary thermodilution (PiCCO, Pulsion Medical Systems, Munich,
      Germany) and continuously received norepinephrine. After baseline, the systolic
      BP was increased (from 105 +/- 10 to 135 +/- 14 mmHg) by briefly increasing the
      norepinephrine dosage and, after a return to baseline level, the tidal volume was
      increased from 6 to 10 ml kg(-1). Final measurements were again taken at baseline
      airway pressures. At each time point, three boluses of 15 ml of 0.9% saline
      solution (<8 degrees C) were injected into a central vein. Fluid status and
      sedation remained unchanged. Friedman ANOVA on ranks for repeated measurements
      was used for statistical analysis. RESULTS: Heart rate (HR), cardiac index,
      intrathoracic blood volume and extravascular lung water remained constant
      throughout. However, the SPV (6 +/- 3 versus 5 +/- 2 mmHg) remained unchanged and
      the SVV decreased (12 +/- 5 versus 10 +/- 4%) with higher BP, whereas both
      parameters, in contrast to central venous and left atrial pressure, significantly
      increased with higher tidal volume. CONCLUSION: In cardiac surgical patients with
      preserved cardiac index, SVV, but not SPV, decreased during an acute increase in
      BP, whereas both parameters, in contrast to cardiac filling pressures,
      significantly increased with higher tidal volume.

PMID- 19401663
TI  - Comparison of two different techniques of fibreoptic intubation.
AB  - BACKGROUND AND OBJECTIVE: The application of analgesics and sedatives during
      fibreoptic intubation (FOI) may result in a transient decrease in arterial oxygen
      saturation.This study evaluates two different techniques of FOI and respective
      effects on procedural duration, arterial oxygen saturation, and coughing by the
      patient. METHODS: Thirty-four patients received a standardized conscious sedation
      with fentanyl (1.5 microg kg(-1)) and midazolam (12.5 microg kg(-1)).All patients
      were randomly allocated to one of the following techniques: the 'vaporization'
      (VAP) technique included four applications of 2 ml lidocaine 2% administered
      through the working channel of the fibrescope supplying an oxygen flow of 3 l
      min(-1); the 'standard' (STAN) technique included the insufflation of 3 l(-1) min
      oxygen via a nasal probe and two applications of 4 ml of lidocaine 2%, each
      followed by a maximum of 2 min to take effect. RESULTS: FOI was successful in all
      patients (STAN 15; 'vaporization' 17 patients). The overall intubation time
      interval was significantly (P < 0.001) shorter in the VAP group. There was no
      difference in oxygen saturation between the two groups prior to the start of FOI,
      but a significant (P = 0.008) decrease in oxygen saturation levels was detected
      in the STAN group after completion of FOI. Patients in the VAP group coughed
      less; a significant difference in the number of coughs (P = 0.036) was found
      during the application of lidocaine into the proximal trachea. CONCLUSION: The
      VAP technique decreases overall intubation time, increases the oxygen saturation
      of the patient until completion of the intubation, and reduces cough.

PMID- 19401664
TI  - Comparison of intravenous and peritonsillar infiltration of tramadol for
      postoperative pain relief in children following adenotonsillectomy.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to compare the postoperative
      analgesic efficacy and side-effects of intravenous tramadol with peritonsillar
      infiltration of tramadol in children undergoing adenotonsillectomy. METHODS:
      Sixty-six children were randomized into two groups: group I received 2 mg kg(-1)
      tramadol intravenously and group II received 2 mg kg(-1) tramadol in 2 ml of
      normal saline (1 ml per tonsil) via peritonsillar infiltration. Modified
      Hannallah pain scale, nausea, vomiting, bleeding, rescue analgesia, sedation and
      Aldrete scores were recorded at the 1st, 15th, 30th and 60th minute
      postoperatively. The Aldrete score was used to determine the postanaesthesia care
      unit discharge criteria. Patients were evaluated for the analgesic requirement,
      nausea and vomiting, bleeding and sedation. RESULTS: There were no differences
      between groups during the first 1 h. In the postanaesthesia care unit, groups I
      and II had comparable pain scores that were not statistically significant (P >
      0.05). But during the first 24 h the additional analgesic requirement of group I
      (141.81 mg) was more than group II (83.63 mg) (P = 0.002). Pain scores in the
      postoperative ward at 6, 12 and 24 h were significantly higher in group I than in
      group II (P < 0.001). Also four patients (12.12%) from group I and one patient
      (3.05%) from group II had nausea and vomiting in the postanaesthesia care unit
      and none of the patients had rescue analgesics. There were no differences between
      groups regarding nausea and vomiting, sedation and bleeding in the postoperative
      ward. CONCLUSION: In adenotonsillectomy cases, peritonsillar infiltration of
      tramadol maintains efficient pain relief with lower incidence of nausea and
      vomiting.

PMID- 19401665
TI  - The effect of remifentanil on the emergence characteristics of children
      undergoing FBO for bronchoalveolar lavage with sevoflurane anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to compare the effects of
      sevoflurane vs. sevoflurane and remifentanil on cough and agitation during
      emergence and recovery after fiberoptic bronchoscopy. METHODS: Children between 2
      and 6 years of age undergoing fiberoptic bronchoscopy were enrolled. All patients
      were premedicated with oral midazolam. Patients were randomly assigned to either
      group S (sevoflurane alone, n = 25) or group SR (sevoflurane with remifetanil, n
      = 25). Anaesthesia was induced and maintained with sevoflurane in all patients.
      Group SR received remifentanil at a bolus dose of 1 microg/kg over 2 min followed
      by a maintenance infusion of 0.15 microg/kg/min. In addition to routine
      anaesthesia documentation, agitation scores and cough scores were recorded every
      5 min during emergence and recovery. RESULTS: Duration of the procedure,
      anaesthesia and emergence phases was similar in both groups (P > 0.05). Time
      until recovery was significantly shorter in group SR than in group S (7.0 +/- 5.5
      min and 13.0 +/- 3.5 min, respectively; P = 0.001). Cough scores were not
      significantly different between the two groups during emergence and recovery
      (Kruskal-Wallis ANOVA test, P > 0.05). However, the mean agitation score at 5 min
      in group SR was significantly higher than that in group S (Kruskal-Wallis ANOVA
      test, P < 0.01). One case of hypoxaemia from thoracic rigidity occurred in a
      patient in group SR. CONCLUSION: The addition of remifentanil significantly
      shortened recovery time in children undergoing fiberoptic bronchoscopy under
      sevoflurane anaesthesia. In the recovery period, remifentanil did not decrease
      cough, and increased agitation.

PMID- 19401666
TI  - Modified Folts models in the rabbit: variations on a well worn theme.

PMID- 19401667
TI  - Comparison between manoeuvres facilitating tube advancement during orotracheal
      fibreoptic intubation, under general anaesthesia.

PMID- 19401668
TI  - Is the decreasing availability of vecuronium and pancuronium putting patients at
      risk?

PMID- 19401669
TI  - Outpatient videothoracoscopic sympathectomy: analgesia and complications.

PMID- 19401670
TI  - Delayed reversal of a potentiated rocuronium neuromuscular block.

PMID- 19401671
TI  - The value of plasma cholinesterase in children with severe liver disease.

PMID- 19401672
TI  - Intubation in patients with acromegaly: experience in more than 800 patients.

PMID- 19401673
TI  - Recombinant vesicular stomatitis virus transduction of dendritic cells enhances
      their ability to prime innate and adaptive antitumor immunity.
AB  - Dendritic cell (DC)-based vaccines are a promising strategy for tumor
      immunotherapy due to their ability to activate both antigen-specific T-cell
      immunity and innate immune effector components, including natural killer (NK)
      cells. However, the optimal mode of antigen delivery and DC activation remains to
      be determined. Using M protein mutant vesicular stomatitis virus (DeltaM51-VSV)
      as a gene-delivery vector, we demonstrate that a high level of transgene
      expression could be achieved in approximately 70% of DCs without affecting cell
      viability. Furthermore, DeltaM51-VSV infection activated DCs to produce
      proinflammatory cytokines (interleukin-12, tumor necrosis factor-alpha, and
      interferon (IFN)alpha/beta), and to display a mature phenotype
      (CD40(high)CD86(high) major histocompatibility complex (MHC II)(high)). When
      delivered to mice bearing 10-day-old lung metastatic tumors, DCs infected with
      DeltaM51-VSV encoding a tumor-associated antigen mediated significant control of
      tumor growth by engaging both NK and CD8(+) T cells. Importantly, depletion of NK
      cells completely abrogated tumor destruction, indicating that NK cells play a
      critical role for this DC vaccine-induced therapeutic outcome. Our findings
      identify DeltaM51-VSV as both an efficient gene-delivery vector and a maturation
      agent allowing DC vaccines to overcome immunosuppression in the tumor-bearing
      host.

PMID- 19401674
TI  - The effect of chemical modification and nanoparticle formulation on stability and
      biodistribution of siRNA in mice.
AB  - Instability and inadequate biodistribution of double-stranded RNA are major
      drawbacks to the clinical use of RNA interference. This work compares chemical
      modification and nanoparticle formulation as strategies to improve the systemic
      delivery of small interfering RNA (siRNA). Variable levels of chemical modified
      siRNA, either naked or within nanoparticle, were intravenously injected into mice
      to study temporal stability and biodistribution detected by direct radioactive
      labeling or by northern blotting. Naked siRNA showed rapid renal clearance, with
      circulatory half-life of <5 minutes that could be extended to >30 minutes by
      cholesterol conjugation. The integrity of the chemically stabilized siRNA was
      maintained in blood for at least 30 minutes, whereas, unmodified siRNA duplex was
      degraded within 1 minute. Intact chemically modified siRNA could also be detected
      in all analyzed organs at 30 minutes but disappeared at 24 hours, except for
      heavy locked nucleic acid (LNA)-modified and cholesterol-conjugated siRNA in the
      lungs. Chitosan, liposomal, or JetPEI formulation greatly improved the stability
      and biodistribution of siRNA. Interestingly, high siRNA accumulation of the
      chitosan/siRNA formulation within the kidney was observed 24 hours
      postadministration. This comparative study highlights improvements to siRNA
      stability and pharmacokinetics, key determinants for development of clinically
      relevant RNAi therapeutics.

PMID- 19401675
TI  - Predicting metabolic biomarkers of human inborn errors of metabolism.
AB  - Early diagnosis of inborn errors of metabolism is commonly performed through
      biofluid metabolomics, which detects specific metabolic biomarkers whose
      concentration is altered due to genomic mutations. The identification of new
      biomarkers is of major importance to biomedical research and is usually performed
      through data mining of metabolomic data. After the recent publication of the
      genome-scale network model of human metabolism, we present a novel computational
      approach for systematically predicting metabolic biomarkers in stochiometric
      metabolic models. Applying the method to predict biomarkers for disruptions of
      red-blood cell metabolism demonstrates a marked correlation with altered
      metabolic concentrations inferred through kinetic model simulations. Applying the
      method to the genome-scale human model reveals a set of 233 metabolites whose
      concentration is predicted to be either elevated or reduced as a result of 176
      possible dysfunctional enzymes. The method's predictions are shown to
      significantly correlate with known disease biomarkers and to predict many novel
      potential biomarkers. Using this method to prioritize metabolite measurement
      experiments to identify new biomarkers can provide an order of a 10-fold increase
      in biomarker detection performance.

PMID- 19401676
TI  - How selection affects phenotypic fluctuation.
AB  - The large degree of phenotypic fluctuation among isogenic cells highlighted by
      recent studies on stochastic gene expression confers fitness on some individuals
      through a 'bet-hedging' strategy, when faced with different selective
      environments. Under a single selective environment, the fluctuation may be
      suppressed through evolution, as it prevents maintenance of individuals around
      the fittest state and/or function. However, as fluctuation can increase
      phenotypic diversity, similar to mutation, it may contribute to the survival of
      individuals even under a single selective environment. To discuss whether the
      fluctuation increases over the course of evolution, cycles of mutation and
      selection for higher GFP fluorescence were carried out in Escherichia coli.
      Mutant genotypes possessing broad GFP fluorescence distributions with low average
      values emerged under strong selection pressure. These 'broad mutants' appeared
      independently on the phylogenetic tree and increased fluctuations in GFP
      fluorescence were attributable to the variance in mRNA abundance. In addition to
      the average phenotypic change by genetic mutation, the observed increase in
      phenotypic fluctuation acts as an evolutionary strategy to produce an extreme
      phenotype under severe selective environments.

PMID- 19401678
TI  - Adaptable gene-specific dye bias correction for two-channel DNA microarrays.
AB  - DNA microarray technology is a powerful tool for monitoring gene expression or
      for finding the location of DNA-bound proteins. DNA microarrays can suffer from
      gene-specific dye bias (GSDB), causing some probes to be affected more by the dye
      than by the sample. This results in large measurement errors, which vary
      considerably for different probes and also across different hybridizations. GSDB
      is not corrected by conventional normalization and has been difficult to address
      systematically because of its variance. We show that GSDB is influenced by label
      incorporation efficiency, explaining the variation of GSDB across different
      hybridizations. A correction method (Gene- And Slide-Specific Correction, GASSCO)
      is presented, whereby sequence-specific corrections are modulated by the overall
      bias of individual hybridizations. GASSCO outperforms earlier methods and works
      well on a variety of publically available datasets covering a range of platforms,
      organisms and applications, including ChIP on chip. A sequence-based model is
      also presented, which predicts which probes will suffer most from GSDB, useful
      for microarray probe design and correction of individual hybridizations. Software
      implementing the method is publicly available.

PMID- 19401677
TI  - Predicting and controlling the reactivity of immune cell populations against
      cancer.
AB  - Heterogeneous cell populations form an interconnected network that determine
      their collective output. One example of such a heterogeneous immune population is
      tumor-infiltrating lymphocytes (TILs), whose output can be measured in terms of
      its reactivity against tumors. While the degree of reactivity varies considerably
      between different TILs, ranging from null to a potent response, the underlying
      network that governs the reactivity is poorly understood. Here, we asked whether
      one can predict and even control this reactivity. To address this we measured the
      subpopulation compositions of 91 TILs surgically removed from 27 metastatic
      melanoma patients. Despite the large number of subpopulations compositions, we
      were able to computationally extract a simple set of subpopulation-based rules
      that accurately predict the degree of reactivity. This raised the conjecture of
      whether one could control reactivity of TILs by manipulating their subpopulation
      composition. Remarkably, by rationally enriching and depleting selected subsets
      of subpopulations, we were able to restore anti-tumor reactivity to nonreactive
      TILs. Altogether, this work describes a general framework for predicting and
      controlling the output of a cell mixture.

PMID- 19401679
TI  - Efficient protein depletion by genetically controlled deprotection of a dormant N
      degron.
AB  - Methods that allow for the manipulation of genes or their products have been
      highly fruitful for biomedical research. Here, we describe a method that allows
      the control of protein abundance by a genetically encoded regulatory system. We
      developed a dormant N-degron that can be attached to the N-terminus of a protein
      of interest. Upon expression of a site-specific protease, the dormant N-degron
      becomes deprotected. The N-degron then targets itself and the attached protein
      for rapid proteasomal degradation through the N-end rule pathway. We use an
      optimized tobacco etch virus (TEV) protease variant combined with selective
      target binding to achieve complete and rapid deprotection of the N-degron-tagged
      proteins. This method, termed TEV protease induced protein inactivation (TIPI) of
      TIPI-degron (TDeg) modified target proteins is fast, reversible, and applicable
      to a broad range of proteins. TIPI of yeast proteins essential for vegetative
      growth causes phenotypes that are close to deletion mutants. The features of the
      TIPI system make it a versatile tool to study protein function in eukaryotes and
      to create new modules for synthetic or systems biology.

PMID- 19401680
TI  - Discovering structural cis-regulatory elements by modeling the behaviors of
      mRNAs.
AB  - Gene expression is regulated at each step from chromatin remodeling through
      translation and degradation. Several known RNA-binding regulatory proteins
      interact with specific RNA secondary structures in addition to specific
      nucleotides. To provide a more comprehensive understanding of the regulation of
      gene expression, we developed an integrative computational approach that
      leverages functional genomics data and nucleotide sequences to discover RNA
      secondary structure-defined cis-regulatory elements (SCREs). We applied our
      structural cis-regulatory element detector (StructRED) to microarray and mRNA
      sequence data from Saccharomyces cerevisiae, Drosophila melanogaster, and Homo
      sapiens. We recovered the known specificities of Vts1p in yeast and Smaug in
      flies. In addition, we discovered six putative SCREs in flies and three in
      humans. We characterized the SCREs based on their condition-specific regulatory
      influences, the annotation of the transcripts that contain them, and their
      locations within transcripts. Overall, we show that modeling functional genomics
      data in terms of combined RNA structure and sequence motifs is an effective
      method for discovering the specificities and regulatory roles of RNA-binding
      proteins.

PMID- 19401681
TI  - Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive
      patients with schizophrenia.
AB  - Schizophrenia is characterized by complex and dynamically interacting
      perturbations in multiple neurochemical systems. In the past, evidence for these
      alterations has been collected piecemeal, limiting our understanding of the
      interactions among relevant biological systems. Earlier, both hyper- and
      hyposerotonemia were variously associated with the longitudinal course of
      schizophrenia, suggesting a disturbance in the central serotonin (5
      hydroxytryptamine (5-HT)) function. Using a targeted electrochemistry-based
      metabolomics platform, we compared metabolic signatures consisting of 13 plasma
      tryptophan (Trp) metabolites simultaneously between first-episode neuroleptic
      naive patients with schizophrenia (FENNS, n=25) and healthy controls (HC, n=30).
      We also compared these metabolites between FENNS at baseline (BL) and 4 weeks
      (4w) after antipsychotic treatment. N-acetylserotonin was increased in FENNS-BL
      compared with HC (P=0.0077, which remained nearly significant after Bonferroni
      correction). N-acetylserotonin/Trp and melatonin (Mel)/serotonin ratios were
      higher, and Mel/N-acetylserotonin ratio was lower in FENNS-BL (all P
      values<0.0029), but not after treatment, compared with HC volunteers. All three
      groups had highly significant correlations between Trp and its metabolites, Mel,
      kynurenine, 3-hydroxykynurenine and tryptamine. However, in the HC, but in
      neither of the FENNS groups, serotonin was highly correlated with Trp, Mel,
      kynurenine or tryptamine, and 5-hydroxyindoleacetic acid (5HIAA) was highly
      correlated with Trp, Mel, kynurenine or 3-hydroxykynurenine. A significant
      difference between HC and FENNS-BL was further shown only for the Trp-5HIAA
      correlation. Thus, some metabolite interactions within the Trp pathway seem to be
      altered in the FENNS-BL patients. Conversion of serotonin to N-acetylserotonin by
      serotonin N-acetyltransferase may be upregulated in FENNS patients, possibly
      related to the observed alteration in Trp-5HIAA correlation. Considering N
      acetylserotonin as a potent antioxidant, such increases in N-acetylserotonin
      might be a compensatory response to increased oxidative stress, implicated in the
      pathogenesis of schizophrenia.

PMID- 19401683
TI  - Prostate cancer-derived urine exosomes: a novel approach to biomarkers for
      prostate cancer.
AB  - Herein, we describe a novel approach in the search for prostate cancer
      biomarkers, which relies on the transcriptome within tumour exosomes. As a proof
      of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3
      and TMPRSS2:ERG the in exosomes isolated from urine of patients, showing the
      potential for diagnosis and monitoring cancer patients status.

PMID- 19401684
TI  - Positive lymph node retrieval ratio optimises patient staging in colorectal
      cancer.
AB  - Alternative lymph node (LN) parameters have been proposed to improve staging in
      colorectal cancer. This study compared these alternative parameters with
      conventional TNM staging in predicting long-term survival in patients undergoing
      curative resection. A total of 295 consecutive patients (mean age 70 years; range
      39-95; s.d. 10.4) underwent resection for colorectal cancer from 2001 to 2004.
      Age, sex, primary tumour site, TNM stage and chemotherapy/radiotherapy were
      recorded. Patients with colon and rectal cancers were analysed separately for LN
      parameters: LN total; adequate LN retrieval (> or =12) and inadequate (<12);
      total number of negative LN; total number of positive LN and the ratio of
      positive LN to total LN (pLNR). Univariate and multivariate survival analysis was
      performed. The median number of LN retrieved was 10 (1-57) with adequate LN
      retrieval in 147 cases (49.8%). For each T and N stage, inadequate LN retrieval
      did not adversely affect long-term survival (P>0.05). On multivariate analysis,
      only pLNR was an independent predictor of overall survival in both colon and
      rectal cancers (HR 11.65, 95% CI 5.00-27.15, P<0.001 and HR 13.40, 95% CI 3.64
      49.10, P<0.001, respectively). Application of pLNR subdivided patients into four
      prognostic groups. Application of the pLNR improved patient stratification in
      colorectal cancer and should be considered in future staging systems.

PMID- 19401682
TI  - High-density SNP association study and copy number variation analysis of the
      AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism
      susceptibility.
AB  - Autism spectrum disorders are a group of highly heritable neurodevelopmental
      disorders with a complex genetic etiology. The International Molecular Genetic
      Study of Autism Consortium previously identified linkage loci on chromosomes 7
      and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high
      density association analysis in AUTS1 and AUTS5, testing more than 3000 single
      nucleotide polymorphisms (SNPs) in all known genes in each region, as well as
      SNPs in non-genic highly conserved sequences. SNP genotype data were also used to
      investigate copy number variation within these regions. The study sample
      consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5
      regions, respectively, and 188 gender-matched controls. Further investigation of
      the strongest association results was conducted in an independent European family
      sample containing 390 affected individuals. Association and copy number variant
      analysis highlighted several genes that warrant further investigation, including
      IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism
      susceptibility was supported by independent replication of association at
      rs2217262 and the finding of a deletion segregating in a sib-pair family.

PMID- 19401685
TI  - Diagnostic precision of image-guided multisampling core needle biopsy of
      suspected lymphomas in a primary care hospital.
AB  - We evaluated the diagnostic quality of image-guided multisampling core needle
      biopsy (CNB) in patients investigated for suspected lymphoma in a primary care
      hospital. A total of 112 patients were consecutively assessed during a 3-year
      period. There were 80 lymphoid site biopsies and 32 non-lymphoid site biopsies.
      Eight to nine cores were obtained from different parts of the biopsy site. Two
      cores were systematically frozen, allowing for further morphological,
      immunochemistry and molecular studies. The diagnostic yield of CNB for malignancy
      was 100%. Only 47% (41/87) of patients with initial suspicion of lymphoma were
      finally diagnosed with Lymphoma. The diagnostic yield of CNB for lymphoma typing
      was 98% (62/63), according to the WHO classification. The diagnostic yield of CNB
      for complete lymphoma subtyping/grading was 86% (54/63). The diagnostic yield of
      CNB for a definite diagnosis of benignity was only 47% (8/17). In a primary care
      setting, multisampling CNB is a minimally invasive, and very accurate procedure
      for confirming malignancy in patients with suspected lymphoma, presenting with
      superficial/deep-seated, lymphoid/non-lymphoid site targets. With a very high
      diagnostic yield for lymphoma typing and a high diagnostic yield for complete
      lymphoma subtyping/grading a therapeutic decision can be taken in most patients.

PMID- 19401686
TI  - Targeting HSP90 for cancer therapy.
AB  - Heat-shock proteins (HSPs) are molecular chaperones that regulate protein folding
      to ensure correct conformation and translocation and to avoid protein
      aggregation. Heat-shock proteins are increased in many solid tumours and
      haematological malignancies. Many oncogenic proteins responsible for the
      transformation of cells to cancerous forms are client proteins of HSP90.
      Targeting HSP90 with chemical inhibitors would degrade these oncogenic proteins,
      and thus serve as useful anticancer agents. This review provides an overview of
      the HSP chaperone machinery and the structure and function of HSP90. We also
      highlight the key oncogenic proteins that are regulated by HSP90 and describe how
      inhibition of HSP90 could alter the activity of multiple signalling proteins,
      receptors and transcriptional factors implicated in carcinogenesis.

PMID- 19401687
TI  - Heterogeneous nuclear ribonucleoprotein K: altered pattern of expression
      associated with diagnosis and prognosis of prostate cancer.
AB  - Using proteomic analysis of the nuclear matrix (NM), we found that heterogeneous
      nuclear ribonucleoprotein K (hnRNP K), a member of the hnRNP family with
      pleiotropic functions, was differentially expressed in prostate cancer (PCa)
      tissues. This study aimed to characterise the expression of hnRNP K and its
      subcellular localisation in PCa, utilising immunohistochemical and quantitative
      western blot techniques. Furthermore, the hnRNP K expression was studied in human
      PCa cell lines in order to determine its modulation by bicalutamide, the anti
      androgen widely used in PCa therapy. Immunohistochemical staining of paraffin
      embedded tissues showed that hnRNP K was overexpressed in PCa, where it was
      localised both in the cytoplasm and in the nucleus. Staining of non-tumour
      tissues showed exclusively nuclear localisation and a less intense or absent
      signal. Immunoblot analysis demonstrated that the hnRNP K level within the NM was
      higher in PCa compared with non-tumour tissues and closely correlated with
      Gleason score (P=0.008). Higher expression within the NM was significantly
      (P=0.032) associated with poor prognosis. In two-dimensional western blot
      analysis hnRNP K presented several isoforms; the one with pI 5.1 was the most
      differently expressed between non-tumour and PCa tissues. Preliminary results
      indicate that hnRNP K can be modulated in vitro by a non-steroidal anti-androgen.
      Taken together, our findings suggest that hnRNP K has potential implications at
      the diagnostic, prognostic and therapeutic levels in PCa.

PMID- 19401689
TI  - CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion.
AB  - The aggressiveness of malignant melanoma is associated with differential
      expression of CXCL-8 and its receptors, CXCR1 and CXCR2. However, the precise
      functional role of these receptors in melanoma progression remains unclear. In
      this study, we investigate the precise functional role of CXCR1 and CXCR2 in
      melanoma progression. CXCR1 or CXCR2 were stably overexpressed in human melanoma
      cell lines, SBC-2 (non-tumourigenic) and A375P (low-tumourigenic) exhibiting low
      endogenous expression of receptors. Functional assays were performed to study the
      resulting changes in cell proliferation, motility and invasion, and in vivo
      tumour growth using a mouse xenograft model. Our data demonstrated that CXCR1- or
      CXCR2-overexpressing SBC-2 and A375P melanoma cells had enhanced proliferation,
      chemotaxis and invasiveness in vitro. Interestingly, CXCR1 or CXCR2
      overexpression in SBC-2 cells induced tumourigenicity, and A375P cells
      significantly enhanced tumour growth as examined in vivo. Immunohistochemical
      analyses showed significantly increased tumour cell proliferation and microvessel
      density and reduced apoptosis in tumours generated from CXCR1- or CXCR2
      overexpressing melanoma cells. CXCR1- or CXCR2-induced modulation of melanoma
      cell proliferation and migration was observed to be mediated through the
      activation of ERK1/2 phosphorylation. Together, these studies demonstrate that
      CXCR1 and CXCR2 play essential role in growth, survival, motility and invasion of
      human melanoma.

PMID- 19401688
TI  - Pattern and quality of care of cancer pain management. Results from the Cancer
      Pain Outcome Research Study Group.
AB  - Most patients with advanced or metastatic cancer experience pain and despite
      several guidelines, undertreatment is well documented. A multicenter, open-label,
      prospective, non-randomised study was launched in Italy in 2006 to evaluate the
      epidemiology, patterns and quality of pain care of cancer patients. To assess the
      adequacy of analgesic care, we used a standardised measure, the pain management
      index (PMI), that compares the most potent analgesic prescribed for a patient
      with the reported level of the worst pain of that patient together with a
      selected list of clinical indicators. A total of 110 centres recruited 1801 valid
      cases. 61% of cases were received a WHO-level III opioid; 25.3% were classified
      as potentially undertreated, with wide variation (9.8-55.3%) according to the
      variables describing patients, centres and pattern of care. After adjustment with
      a multivariable logistic regression model, type of recruiting centre, receiving
      adjuvant therapy or not and type of patient recruited (new or already on follow
      up) had a significant association with undertreatment. Non-compliance with the
      predefined set of clinical indicators was generally high, ranging from 41 to 76%.
      Despite intrinsic limitations of the PMI that may be considered as an indicator
      of the poor quality of cancer pain care, results suggest that the recourse to WHO
      third-level drugs still seems delayed in a substantial percentage of patients.
      This delay is probably related to several factors affecting practice in
      participating centres and suggests that the quality of cancer pain management in
      Italy deserves specific attention and interventions aimed at improving patients'
      outcomes.

PMID- 19401690
TI  - Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone
      marrow, blood and stem cell preparations by immunocytology and QRT-PCR:
      recommendations by the International Neuroblastoma Risk Group Task Force.
AB  - Disseminating disease is a predictive and prognostic indicator of poor outcome in
      children with neuroblastoma. Its accurate and sensitive assessment can facilitate
      optimal treatment decisions. The International Neuroblastoma Risk Group (INRG)
      Task Force has defined standardised methods for the determination of minimal
      disease (MD) by immunocytology (IC) and quantitative reverse transcriptase
      polymerase chain reaction (QRT-PCR) using disialoganglioside G(D2) and tyrosine
      hydroxylase mRNA respectively. The INRG standard operating procedures (SOPs)
      define methods for collecting, processing and evaluating bone marrow (BM),
      peripheral blood (PB) and peripheral blood stem cell harvest by IC and QRT-PCR.
      Sampling PB and BM is recommended at diagnosis, before and after myeloablative
      therapy and at the end of treatment. Peripheral blood stem cell products should
      be analysed at the time of harvest. Performing MD detection according to INRG
      SOPs will enable laboratories throughout the world to compare their results and
      thus facilitate quality-controlled multi-centre prospective trials to assess the
      clinical significance of MD and minimal residual disease in heterogeneous patient
      groups.

PMID- 19401691
TI  - TGFBR1 variants TGFBR1(*)6A and Int7G24A are not associated with an increased
      familial colorectal cancer risk.
AB  - Variants of the transforming growth factor-beta receptor type 1 (TGFBR1) gene,
      TGFBR1*6A and Int7G24A, have been suggested to act as low-penetrance tumour
      susceptibility alleles with TGFBR1*6A being causally responsible for some cases
      of familial colorectal cancer (CRC). We performed a case-control study of 262
      unrelated familial CRC cases; 83 hereditary non-polyposis colorectal cancer
      (HNPCC) and 179 non-HNPCC. Patients were genotyped for TGFBR1*6A and Int7G24A and
      compared with 856 controls. Further, we screened the coding region of TGFBR1 in
      affected members of a large family with CRC linked to 9q22.32-31.1. TGFBR1*6A
      allelic frequency was not significantly different in all of the familial cases
      compared with controls (0.107 and 0.106, respectively; P=0.915). In a subgroup
      analysis allele frequencies were, however, different between HNPCC and non-HNPCC
      familial cases (0.157 and 0.084, respectively; P=0.013). TGFBR1*6A genotype did
      not influence age of onset. Int7G24A allele frequencies were similar in cases and
      controls. No germ-line mutation was identified in the family with CRC linked to
      this chromosomal region. Our study provides no substantial support for the
      hypothesis that the polymorphic variants TGFBR1*6A or Int7G24A contribute to
      familial CRC risk. We cannot, however, exclude the possibility that TGFBR1
      variants have a modifying effect on inherited risk per se.

PMID- 19401693
TI  - Prevalent cases in observational studies of cancer survival: do they bias hazard
      ratio estimates?
AB  - Observational epidemiological studies often include prevalent cases recruited at
      various times past diagnosis. This left truncation can be dealt with in non
      parametric (Kaplan-Meier) and semi-parametric (Cox) time-to-event analyses,
      theoretically generating an unbiased hazard ratio (HR) when the proportional
      hazards (PH) assumption holds. However, concern remains that inclusion of
      prevalent cases in survival analysis results inevitably in HR bias. We used data
      on three well-established breast cancer prognosticators - clinical stage,
      histopathological grade and oestrogen receptor (ER) status - from the SEARCH
      study, a population-based study including 4470 invasive breast cancer cases
      (incident and prevalent), to evaluate empirically the effectiveness of allowing
      for left truncation in limiting HR bias. We found that HRs of prognostic factors
      changed over time and used extended Cox models incorporating time-dependent
      covariates. When comparing Cox models restricted to subjects ascertained within
      six months of diagnosis (incident cases) to models based on the full data set
      allowing for left truncation, we found no difference in parameter estimates
      (P=0.90, 0.32 and 0.95, for stage, grade and ER status respectively). Our results
      show that use of prevalent cases in an observational epidemiological study of
      breast cancer does not bias the HR in a left truncation Cox survival analysis,
      provided the PH assumption holds true.

PMID- 19401692
TI  - Activation of Wnt/beta-catenin signalling pathway induces chemoresistance to
      interferon-alpha/5-fluorouracil combination therapy for hepatocellular carcinoma.
AB  - Type I IFN receptor type 2 (IFNAR2) expression correlates significantly with
      clinical response to interferon (IFN)-alpha/5-fluorouracil (5-FU) combination
      therapy for hepatocellular carcinoma (HCC). However, some IFNAR2-positive
      patients show no response to the therapy. This result suggests the possibility of
      other factors, which would be responsible for resistance to IFN-alpha/5-FU
      therapy. The aim of this study was to examine the mechanism of anti-proliferative
      effects of IFN-alpha/5-FU therapy and search for a biological marker of
      chemoresistance to such therapy. Gene expression profiling and molecular network
      analysis were used in the analysis of non-responders and responders with IFNAR2
      positive HCC. The Wnt/beta-catenin signalling pathway contributed to resistance
      to IFN-alpha/5-FU therapy. Immunohistochemical analysis showed positive
      epithelial cell adhesion molecule (Ep-CAM) expression, the target molecule of
      Wnt/beta-catenin signalling, only in non-responders. In vitro studies showed that
      activation of Wnt/beta-catenin signalling by glycogen synthesis kinase-3
      inhibitor (6-bromoindirubin-3'-oxime (BIO)) induced chemoresistance to IFN
      alpha/5-FU. BrdU-based cell proliferation ELISA and cell cycle analysis showed
      that concurrent addition of BIO and IFN-alpha/5-FU significantly to hepatoma cell
      cultures reduced the inhibitory effects of the latter two on DNA synthesis and
      accumulation of cells in the S-phase. The results indicate that activation of
      Wnt/beta-catenin signalling pathway induces chemoresistance to IFN-alpha/5-FU
      therapy and suggest that Ep-CAM is a potentially useful marker for resistance to
      such therapy, especially in IFNAR2-positive cases.

PMID- 19401695
TI  - Correlation of RET somatic mutations with clinicopathological features in
      sporadic medullary thyroid carcinomas.
AB  - Screening of REarranged during Transfection (RET) gene mutations has been carried
      out in different series of sporadic medullary thyroid carcinomas (MTC). RET
      positive tumours seem to be associated to a worse clinical outcome. However, the
      correlation between the type of RET mutation and the patients'
      clinicopathological data has not been evaluated yet. We analysed RET exons 5, 8,
      10-16 in fifty-one sporadic MTC, and found somatic mutations in thirty-three
      (64.7%) tumours. Among the RET-positive cases, exon 16 was the most frequently
      affected (60.6%). Two novel somatic mutations (Cys630Gly, c.1881del18) were
      identified. MTC patients were divided into three groups: group 1, with mutations
      in RET exons 15 and 16; group 2, with other RET mutations; group 3, having no RET
      mutations. Group 1 had higher prevalence (P=0.0051) and number of lymph node
      metastases (P=0.0017), and presented more often multifocal tumours (P=0.037) and
      persistent disease at last control (P=0.0242) than group 2. Detectable serum
      calcitonin levels at last screening (P=0.0119) and stage IV disease (P=0.0145)
      were more frequent in group 1, than in the other groups. Our results suggest
      that, among the sporadic MTC, cases with RET mutations in exons 15 and 16 are
      associated with the worst prognosis. Cases with other RET mutations have the most
      indolent course, and those with no RET mutations have an intermediate risk.

PMID- 19401694
TI  - Prophylactic ciprofloxacin treatment prevented high mortality, and modified
      systemic and intestinal immune function in tumour-bearing rats receiving dose
      intensive CPT-11 chemotherapy.
AB  - Infectious complications are a major cause of morbidity and mortality from dose
      intensive cancer chemotherapy. In spite of the importance of intestinal bacteria
      translocation in these infections, information about the effect of high-dose
      chemotherapy on gut mucosal immunity is minimal. We studied prophylactic
      ciprofloxacin (Cipro) treatment on irinotecan (CPT-11) toxicity and host immunity
      in rats bearing Ward colon tumour. Cipro abolished chemotherapy-related
      mortality, which was 45% in animals that were not treated with Cipro. Although
      Cipro reduced body weight loss and muscle wasting, it was unable to prevent
      severe late-onset diarrhoea. Seven days after CPT-11, splenocytes were unable to
      proliferate (stimulation index=0.10+/-0.02) and produce proliferative and
      inflammatory cytokines (i.e., Interleukin (IL)-2, interferon-gamma (IFN-gamma),
      tumour necrosis factor-alpha (TNF-alpha) IL-1beta, IL-6) on mitogen stimulation
      in vitro (P<0.05 vs controls), whereas mesenteric lymph node (MLN) cells showed a
      hyper-proliferative response and a hyper-production of pro-inflammatory cytokines
      on mitogen stimulation. This suggests compartmentalised effects by CPT-11
      chemotherapy on systemic and intestinal immunity. Cipro normalised the hyper
      responsiveness of MLN cells, and in the spleen, it partially restored the
      proliferative response and normalised depressed production of IL-1beta and IL-6.
      Taken together, Cipro prevented infectious challenges associated with immune hypo
      responsiveness in systemic immune compartments, and it may also alleviate
      excessive pro-inflammatory responses mediating local gut injury.

PMID- 19401696
TI  - Clinical benefit in Phase-I trials of novel molecularly targeted agents: does
      dose matter?
AB  - Phase-I trials traditionally involve dose-escalation to determine the maximal
      tolerated dose (MTD). With conventional chemotherapy, efficacy is generally
      deemed to be dose-dependent, but the same may not be applicable to molecularly
      targeted agents (MTAs). We analysed consecutive patients included in Phase-I
      trials at the Royal Marsden Hospital from 5 January 2005 to 6 June 2006. We
      considered only trials of monotherapy MTAs in which the MTD was defined. Three
      patient cohorts (A, B, and C) were identified according to the dose received as a
      percentage of the final trial MTD (0-33%, 34-65%, >66%). Potential efficacy was
      assessed using the non-progression rate (NPR), that is, complete/partial response
      or stable disease for at least 3 months by RECIST. A total of 135 patients having
      progressive disease before enrolment were analysed from 15 eligible trials.
      Median age was 57 years (20-86); male : female ratio was 1.8 : 1. Cohort A, B,
      and C included 28 (21%), 22 (16%), and 85 (63%) patients; NPR at 3 and 6 months
      was 21% and 11% (A), 50% and 27% (B), 31% and 14% (C), respectively, P=0.9.
      Median duration of non-progression (17 weeks; 95% CI=13-22) was not correlated
      with the MTD level, P=0.9. Our analysis suggests that the potential for clinical
      benefit is not confined to patients treated at doses close to the MTD in Phase-I
      trials of MTAs.

PMID- 19401697
TI  - Phase I study of bortezomib and cetuximab in patients with solid tumours
      expressing epidermal growth factor receptor.
AB  - Bortezomib inhibits nuclear factor-kappaB (NF-kappaB). Cetuximab is a chimeric
      mouse-human antibody targeted against epidermal growth factor receptor (EGFR). We
      hypothesised that concomitant blockade of NF-kappaB and EGFR signalling would
      overcome EGFR-mediated resistance to single-agent bortezomib and induce apoptosis
      through two molecular pathways. The aim of this phase I trial was to establish
      the maximum tolerated dose (MTD) for bortezomib plus cetuximab in patients with
      EGFR-expressing epithelial tumours. The 21-day treatment cycle consisted of
      bortezomib administered on days 1 and 8 through dose escalation (1.3-2 mg m(-2)).
      Cetuximab was delivered at a dose of 250 mg m(-2) on days 1, 8 and 15 (400 mg m(
      2) day 1 cycle 1). A total of 37 patients were enroled and given a total 91
      cycles. No grade > or =3 haematological toxicity was noted. Non-hematological
      grade > or =3 toxicities included fatigue (22% of patients), dyspnoea (16%) and
      infection (11%). The MTD was not reached at the highest tested bortezomib dose
      (2.0 mg m(-2)). Efficacy outcomes included disease progression in 21 patients
      (56.7%) and stable disease (SD) at 6 weeks in 16 patients (43.3%). Five of the
      six patients with SD at 12 weeks were diagnosed with cancers of the lungs or head
      and neck. This combination therapy was moderately effective in extensively
      pretreated patients with non-small cell lung or head and neck cancers and
      warrants further investigation.

PMID- 19401698
TI  - Prognostic role of vascular endothelial growth factor in hepatocellular
      carcinoma: systematic review and meta-analysis.
AB  - Hepatocellular carcinoma (HCC) is a highly vascular tumour that expresses
      vascular endothelial growth factor (VEGF). Various studies have evaluated the
      prognostic value of VEGF levels in HCC. Its overall test performance remains
      unclear, however. The aim was to perform a systematic review and meta-analysis of
      prognostic cohort studies evaluating the use of VEGF as a predictor of survival
      in patients with treated HCC. Eligible studies were identified through multiple
      search strategies. Studies were assessed for quality using the Newcastle-Ottawa
      Tool. Data were collected comparing disease-free and overall survival in patients
      with high VEGF levels as compared to those with low levels. Studies were pooled
      and summary hazard ratios were calculated. A total of 16 studies were included
      for meta-analysis (8 for tissue and 8 for serum). Methodological analysis
      indicated a trend for higher study quality with serum studies as compared to
      tissue-based investigations. Four distinct groups were pooled for analysis:
      tissue overall survival (n=251), tissue disease-free survival (n=413), serum
      overall survival (n=579), and serum disease-free survival (n=439). High tissue
      VEGF levels predicted poor overall (HR=2.15, 95% CI: 1.26-3.68) and disease-free
      (HR=1.69, 95% CI: 1.23-2.33) survival. Similarly, high serum VEGF levels
      predicted poor overall (HR=2.35, 95% CI: 1.80-3.07) and disease-free (HR=2.36,
      95% CI 1.76-3.16) survival. A high degree of inter-study consistency was present
      in three of four groups analysed. Tissue and serum VEGF levels appear to have
      significant predictive ability for estimating overall survival in HCC and may be
      useful for defining prognosis in HCC.

PMID- 19401699
TI  - Radical hysterectomy for FIGO stage I-IIB adenocarcinoma of the uterine cervix.
AB  - A retrospective analysis was carried out to identify risk factors for survival
      and relapse in patients with FIGO stage I-IIB cervical adenocarcinoma (AC), who
      underwent radical hysterectomy, and to compare outcome and spread pattern with
      those of squamous cell carcinoma (SCC). One hundred and twenty-three FIGO stage I
      IIB patients with AC and 455 patients with SCC, who all underwent primary radical
      hysterectomy, were reviewed. Among the patients with AC, Cox model identified
      tumour size (95% CI: 1.35-30.71) and node metastasis (95% CI: 5.09-53.44) as
      independent prognostic factors for survival, and infiltration to vagina (95% CI:
      1.15-5.76) and node metastasis (95% CI: 6.39-58.87) as independent prognostic
      factors for relapse. No significant difference was found in survival or relapse
      between the AC and SCC groups, after adjusting for other clinicopathological
      characteristics using Cox model. No significant difference was found in the
      positive rates of lymph nodes or location of initial failure sites between the
      two groups, but ovarian metastatic rate was significantly higher in patients with
      pathologic stage IIB AC (P=0.02). Positive node is a common independent
      prognostic factor for survival and relapse of patients with AC. FIGO stage I-IIB
      patients with AC or SCC, who underwent radical hysterectomy, have similar
      prognosis and spread pattern, but different ovarian metastasis rates.

PMID- 19401700
TI  - Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway.
AB  - Chordomas are radio- and chemo-resistant tumours and metastasise in as many as
      40% of patients. The aim of this study was to identify potential molecular
      targets for the treatment of chordoma. In view of the reported association of
      chordoma and tuberous sclerosis complex syndrome, and the available therapeutic
      agents against molecules in the PI3K/AKT/TSC1/TSC2/mTOR pathway, a tissue
      microarray of 50 chordoma cases was analysed for expression of active molecules
      involved in this signalling pathway by immunohistochemistry and a selected number
      by western blot analysis. Chordomas were positive for p-AKT (92%), p-TSC2 (96%),
      p-mTOR (27%), total mTOR (75%), p-p70S6K (62%), p-RPS6 (22%), p-4E-BP1 (96%) and
      eIF-4E (98%). Phosphatase and tensin homologue deleted on chromosome 10
      expression was lost in 16% of cases. Mutations failed to be identified in PI3KCA
      and RHEB1 in the 23 cases for which genomic DNA was available. Fluorescence in
      situ hybridisation analysis for mTOR and RPS6 loci showed that 11 of 33 and 21 of
      44 tumours had loss of one copy of the respective genes, results which correlated
      with the loss of the relevant total proteins. Fluorescence in situ hybridisation
      analysis for loci containing TSC1 and TSC2 revealed that all cases analysed
      harboured two copies of the respective genes. On the basis of p-mTOR and or p
      p70S6K expression there is evidence indicating that 65% of the chordomas studied
      may be responsive to mTOR inhibitors, rapamycin or its analogues, and that
      patients may benefit from combined therapy including drugs that inhibit AKT.

PMID- 19401701
TI  - Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in
      human pancreatic cancer cells.
AB  - Curcumin has been shown to inhibit the growth of various types of cancer cells;
      however, at concentrations much above the clinically achievable levels in humans.
      The concentration of curcumin achieved in the plasma after oral administration in
      humans was estimated to be around 1.8 microM. Here, we report that treatment of
      BxPC-3 human pancreatic cancer cells with a low and single exposure of 2.5 microM
      curcumin for 24 h causes significant arrest of cells in the G2/M phase and
      induces significant apoptosis. Immunoblot studies revealed increased
      phosphorylation of H2A.X at Ser-139 and Chk1 at Ser-280 and a decrease in DNA
      polymerase-beta level in curcumin-treated cells. Phosphorylation of H2A.X and
      Chk1 proteins are an indicator of DNA damage whereas DNA polymerase-beta plays a
      role in the repair of DNA strand breaks. Normal immortalised human pancreatic
      ductal epithelial (HPDE-6) cells remained unaffected by curcumin treatment. In
      addition, we also observed a significant increase in the phosphorylation of Chk1
      at Ser-345, Cdc25C at Ser-216 and a subtle increase in ATM phosphorylation at Ser
      1981. Concomitant decrease in the expressions of cyclin B1 and Cdk1 were seen in
      curcumin-treated cells. Further, curcumin treatment caused significant cleavage
      of caspase-3 and PARP in BxPC-3 but not in HPDE-6 cells. Silencing ATM/Chk1
      expression by transfecting BxPC-3 cells with ATM or Chk1-specific SiRNA blocked
      the phosphorylation of ATM, Chk1 and Cdc25C and protected the cells from curcumin
      mediated G2/M arrest and apoptosis. This study reflects the critical role of
      ATM/Chk1 in curcumin-mediated G2/M cell cycle arrest and apoptosis in pancreatic
      cancer cells.

PMID- 19401702
TI  - Analysis of differential gene expression in colorectal cancer and stroma using
      fluorescence-activated cell sorting purification.
AB  - Tumour stroma gene expression in biopsy specimens may obscure the expression of
      tumour parenchyma, hampering the predictive power of microarrays. We aimed to
      assess the utility of fluorescence-activated cell sorting (FACS) for generating
      cell populations for gene expression analysis and to compare the gene expression
      of FACS-purified tumour parenchyma to that of whole tumour biopsies. Single cell
      suspensions were generated from colorectal tumour biopsies and tumour parenchyma
      was separated using FACS. Fluorescence-activated cell sorting allowed reliable
      estimation and purification of cell populations, generating parenchymal purity
      above 90%. RNA from FACS-purified and corresponding whole tumour biopsies was
      hybridised to Affymetrix oligonucleotide microarrays. Whole tumour and
      parenchymal samples demonstrated differential gene expression, with 289 genes
      significantly overexpressed in the whole tumour, many of which were consistent
      with stromal gene expression (e.g., COL6A3, COL1A2, POSTN, TIMP2). Genes
      characteristic of colorectal carcinoma were overexpressed in the FACS-purified
      cells (e.g., HOX2D and RHOB). We found FACS to be a robust method for generating
      samples for gene expression analysis, allowing simultaneous assessment of
      parenchymal and stromal compartments. Gross stromal contamination may affect the
      interpretation of cancer gene expression microarray experiments, with
      implications for hypotheses generation and the stability of expression signatures
      used for predicting clinical outcomes.

PMID- 19401704
TI  - Cancer risks in first-degree relatives of CHEK2 mutation carriers: effects of
      mutation type and cancer site in proband.
AB  - It is important to have accurate knowledge of the range of cancers associated
      with various CHEK2 mutations, and of the lifetime risks of cancer associated with
      each. We wished to establish the relationship between family history, mutation
      type and cancer risk in families with a CHEK2 mutation. We obtained a blood
      sample and pedigree information from 2012 unselected women with breast cancer,
      from 2007 men with prostate cancer and from 1934 patients with colon cancer, from
      hospitals throughout Poland. Genetic testing was carried out for four founder
      CHEK2 mutations on all 5953 specimens and 533 carriers were identified. We
      estimated the risk to age 75 for any cancer in the 2544 first-degree relatives to
      be 22.3%. After adjusting for mutation type, the risk of breast cancer was much
      higher among relatives of probands with breast cancer than among relatives of
      patients with prostate or colon cancer (HR=3.6; 95% CI=2.1-6.2; P=0.0001).
      Similarly, the risk of prostate cancer was higher among relatives of probands
      with prostate cancer than among relatives of patients with breast or colon cancer
      (HR=4.4; 95% CI=2.2-8.7; P=0.0001) and the risk of colon cancer was higher among
      relatives of probands with colon cancer than among relatives of patients with
      prostate or breast cancer (HR=4.2; 95% CI=2.4-7.8; P=0.0001). These analyses
      suggest that the risk of cancer in a carrier of a CHEK2 mutation is dependent on
      the family history of cancer.

PMID- 19401703
TI  - International consensus for neuroblastoma molecular diagnostics: report from the
      International Neuroblastoma Risk Group (INRG) Biology Committee.
AB  - Neuroblastoma serves as a paradigm for utilising tumour genomic data for
      determining patient prognosis and treatment allocation. However, before the
      establishment of the International Neuroblastoma Risk Group (INRG) Task Force in
      2004, international consensus on markers, methodology, and data interpretation
      did not exist, compromising the reliability of decisive genetic markers and
      inhibiting translational research efforts. The objectives of the INRG Biology
      Committee were to identify highly prognostic genetic aberrations to be included
      in the new INRG risk classification schema and to develop precise definitions,
      decisive biomarkers, and technique standardisation. The review of the INRG
      database (n=8800 patients) by the INRG Task Force finally enabled the
      identification of the most significant neuroblastoma biomarkers. In addition, the
      Biology Committee compared the standard operating procedures of different
      cooperative groups to arrive at international consensus for methodology,
      nomenclature, and future directions. Consensus was reached to include MYCN
      status, 11q23 allelic status, and ploidy in the INRG classification system on the
      basis of an evidence-based review of the INRG database. Standardised operating
      procedures for analysing these genetic factors were adopted, and criteria for
      proper nomenclature were developed. Neuroblastoma treatment planning is highly
      dependant on tumour cell genomic features, and it is likely that a comprehensive
      panel of DNA-based biomarkers will be used in future risk assignment algorithms
      applying genome-wide techniques. Consensus on methodology and interpretation is
      essential for uniform INRG classification and will greatly facilitate
      international and cooperative clinical and translational research studies.

PMID- 19401705
TI  - Cost analysis for cancer subgroups.

PMID- 19401708
TI  - Signal separation and parameter estimation in noninvasive dual-tracer PET scans
      using reference-region approaches.
AB  - This is the first study to report results from a noninvasive dual-tracer positron
      emission tomography (PET) in humans not requiring arterial sampling, in which two
      radiotracers were injected closely in time within the same scan. These studies
      yield near simultaneous information on two different neuropharmacological
      systems, providing better characterization of a subject's neurologic condition.
      The noninvasive dual-tracer approach described in this study is based on the
      primary assumption that an appropriate bolus plus constant infusion protocol
      brings the reference tissue of the first radiotracer to steady state before
      injection of the second tracer. Two methods for separation of time-activity
      curves (TACs) and parameter estimation were investigated, namely (1) an
      extrapolation method, in which TACs of the first tracer were extrapolated over
      total scan duration followed by subtraction from dual-tracer TACs and (2) a
      simultaneous fitting method, in which reference-region models for both tracers
      were fitted simultaneously to dual-tracer TACs. Combinations of two reversible
      tracers ([(11)C]flumazenil and [(11)C]dihydrotetrabenazine) or one reversible and
      one irreversible tracer ([(11)C]N-methylpiperidinyl propionate) were used. After
      the dual-tracer scan, a single-tracer (ST) scan using one of the tracers was
      obtained for comparison of the dual-tracer results. Both approaches provided
      parameter estimates with intersubject regions-of-interest means typically within
      10% of those obtained from ST scans without an appreciable increase in variance.

PMID- 19401710
TI  - Enhanced cerebral expression of MCT1 and MCT2 in a rat ischemia model occurs in
      activated microglial cells.
AB  - Monocarboxylate transporters (MCTs) are essential for the use of lactate, an
      energy substrate known to be overproduced in brain during an ischemic episode.
      The expression of MCT1 and MCT2 was investigated at 48 h of reperfusion from
      focal ischemia induced by unilateral extradural compression in Wistar rats.
      Increased MCT1 mRNA expression was detected in the injured cortex and hippocampus
      of compressed animals compared to sham controls. In the contralateral,
      uncompressed hemisphere, increases in MCT1 mRNA level in the cortex and MCT2 mRNA
      level in the hippocampus were noted. Interestingly, strong MCT1 and MCT2 protein
      expression was found in peri-lesional macrophages/microglia and in an isolectin
      B4+/S100beta+ cell population in the corpus callosum. In vitro, MCT1 and MCT2
      protein expression was observed in the N11 microglial cell line, whereas an
      enhancement of MCT1 expression by tumor necrosis factor-alpha (TNF-alpha) was
      shown in these cells. Modulation of MCT expression in microglia suggests that
      these transporters may help sustain microglial functions during recovery from
      focal brain ischemia. Overall, our study indicates that changes in MCT expression
      around and also away from the ischemic area, both at the mRNA and protein levels,
      are a part of the metabolic adaptations taking place in the brain after ischemia.

PMID- 19401709
TI  - Therapeutic neutralization of the NLRP1 inflammasome reduces the innate immune
      response and improves histopathology after traumatic brain injury.
AB  - Traumatic brain injury elicits acute inflammation that in turn exacerbates
      primary brain damage. A crucial part of innate immunity in the immune privileged
      central nervous system involves production of proinflammatory cytokines mediated
      by inflammasome signaling. Here, we show that the nucleotide-binding, leucine
      rich repeat pyrin domain containing protein 1 (NLRP1) inflammasome consisting of
      NLRP1, caspase-1, caspase-11, apoptosis-associated speck-like protein containing
      a caspase recruitment domain (ASC), the X-linked inhibitor of apoptosis protein,
      and pannexin 1 is expressed in neurons of the cerebral cortex. Moderate
      parasagittal fluid-percussion injury (FPI) induced processing of interleukin
      1beta, activation of caspase-1, cleavage of X-linked inhibitor of apoptosis
      protein, and promoted assembly of the NLRP1 inflammasome complex. Anti-ASC
      neutralizing antibodies administered immediately after fluid-percussion injury to
      injured rats reduced caspase-1 activation, X-linked inhibitor of apoptosis
      protein cleavage, and processing of interleukin-1beta, resulting in a significant
      decrease in contusion volume. These studies show that the NLRP1 inflammasome
      constitutes an important component of the innate central nervous system
      inflammatory response after traumatic brain injury and may be a novel therapeutic
      target for reducing the damaging effects of posttraumatic brain inflammation.

PMID- 19401712
TI  - Complex postglacial history of the temperate bark beetle Tomicus piniperda L.
      (Coleoptera, Scolytinae).
AB  - Tomicus piniperda is an economically important pine bark beetle infesting
      European Pinus spp. stands. We sequenced and analyzed 797 bp of the mitochondrial
      genome from individuals obtained from 34 populations sampled throughout the
      European range. We obtained 36 haplotypes, from which a haplotype network was
      constructed. In the Iberian Peninsula, high-genetic variability was detected with
      numerous endemic haplotypes. In contrast, the other European populations were
      less diverse with a single haplotype predominating from the Pyrenees to
      Scandinavia. Nevertheless, even within Europe, a few populations showed
      significant amounts of diversity. Four groups were obtained by Spatial Analysis
      of Molecular Variance, illustrating the regional characteristics of the species.
      T. piniperda had multiple fragmented refugia in the Iberian Peninsula. These
      currently isolated populations only partly contributed to postglacial re
      colonizations of Northern Europe during interglacials. Nevertheless, few long
      range migration events up to Northern Europe were detected, mostly originating
      from the Pyrenees. In the rest of Europe, the phylogeographical patterns were
      unclear, because of repeated cycles of contraction and expansion. The genetic
      analysis showed one glacial refugium in North-Central Europe, whereas other
      refugia most likely occurred in the Southern Alps, Apennine and the Balkans. The
      phylogeographical pattern depicted here reflects partly the postglacial history
      of the beetles' main host tree P. sylvestris.

PMID- 19401711
TI  - Quantitative genetic variation in the control of ovarian apoptosis under
      different environments.
AB  - Fertility loss in otherwise healthy individuals can be an evolutionary conundrum.
      Most studies on the evolution of post-reproductive lifespan focus on the fitness
      effects of survival past the age of last reproduction. A complementary approach,
      which has been largely neglected, is to develop an understanding of the nature of
      variation in the mechanism underlying loss of fertility, ovarian apoptosis.
      Variation in the genetics underlying the regulation of ovarian apoptosis could
      hold the key to understanding the evolution of midlife fertility loss. We
      estimated quantitative genetic variation in the regulation of ovarian apoptosis
      in females of the cockroach Nauphoeta cinerea, an insect with reproductive
      cycles. We have earlier shown that delaying reproduction incites loss of
      fertility. Here, we forced females to delay reproduction under conditions of
      excess or limited food and examined apoptosis under both conditions. We found
      substantial additive genetic variation in levels of apoptosis when females
      experienced a limited period of starvation during sexual maturation but not when
      females had unlimited access to food. Hence, selection could act on the
      regulation of ovarian apoptosis to change the rate of fertility loss with age at
      least under some environmental circumstances. Our results suggest that an
      understanding of how loss of fertility evolves requires an understanding of the
      interaction between genes involved in the regulation of apoptosis and
      environmental factors such as diet.

PMID- 19401713
TI  - Transposons in the MHC: the Yin and Yang of the vertebrate immune system.

PMID- 19401714
TI  - Coil and shape in Partula suturalis: the rules of form revisited.
AB  - Early research on the direction of coiling (chirality) in snails had a prominent
      role in the history of biology, and continues to mold current thinking about
      developmental evolution. Here, we investigated the pleiotropic effects of
      chirality alleles on shell shape and length, using a large set of data from the
      Polynesian land snail Partula suturalis. By examining the shells of individuals
      with different combinations of their own and their mother's chiral genotypes, we
      find that the effects of chiral genes on length and shape involve both the
      maternal genotype and the genotype of the individual itself. Thus, differences in
      shape are symptoms of developmental shifts caused by the chirality alleles, or by
      alleles at other loci in close linkage disequilibrium with them. Although changes
      in shell shape are not necessary concomitants of chiral evolution, the results
      illustrate the wider pleiotropic effects of the genes, or haplotypes, that
      influence chirality. As the data are a rare record of the association in nature
      between the phenotype and genotype of a locus showing maternal effects, the
      conclusions are likely to be relevant to the general understanding of the
      dynamics of maternal-effect genes, including how selection acts on them.

PMID- 19401715
TI  - Mitochondrial DNA signatures at different spatial scales: from the effects of the
      Straits of Gibraltar to population structure in the meridional serotine bat
      (Eptesicus isabellinus).
AB  - The meridional serotine bat Eptesicus isabellinus is found in North Africa and
      the Iberian Peninsula. We analyzed the genetic structure of E. isabellinus at two
      different geographic scales to reveal the historical and ecological patterns that
      have shaped its populations. The role of the Straits of Gibraltar as an isolating
      barrier between African and Iberian populations is evaluated and the degree of
      genetic structure and female-mediated gene flow was assessed at a local scale
      between neighboring colonies. Populations of E. isabellinus from Iberia and
      northern Morocco show little genetic divergence and share mtDNA haplotypes,
      indicating that the Straits of Gibraltar are neither an impediment to dispersal
      nor a cause of genetic differentiation. Our results also suggest that E.
      isabellinus may have dispersed from western Andalusia into northern Morocco after
      the last glacial period. At a smaller geographic scale, the colonies studied
      showed high variation in genetic variability and structure, indicating that no
      female-mediated gene flow is present. This pattern is consistent with a described
      pattern of independent endemic viral circulation of the bat rabies virus EBLV-1,
      which was found when studying rabies dynamics in the same serotine bat colonies.

PMID- 19401716
TI  - Split hand/foot malformation due to chromosome 7q aberrations(SHFM1): additional
      support for functional haploinsufficiency as the causative mechanism.
AB  - We report on three patients with split hand/foot malformation type 1 (SHFM1). We
      detected a deletion in two patients and an inversion in the third, all involving
      chromosome 7q21q22. We performed conventional chromosomal analysis, array
      comparative genomic hybridization and fluorescence in situ hybridization. Both
      deletions included the known genes associated with SHFM1 (DLX5, DLX6 and DSS1),
      whereas in the third patient one of the inversion break points was located just
      centromeric to these genes. These observations confirm that haploinsufficiency
      due to either a simultaneous deletion of these genes or combined downregulation
      of gene expression due to a disruption in the region between these genes and a
      control element could be the cause of the syndrome. We review previously reported
      studies that support this hypothetical mechanism.

PMID- 19401717
TI  - Lessons from cutis laxa syndromes: wrinkles due to improper reloading of the
      extracellular matrix?

PMID- 19401718
TI  - Direct to consumer genetic tests.

PMID- 19401719
TI  - Autosomal recessive cutis laxa syndrome revisited.
AB  - The clinical spectrum of the autosomal recessive cutis laxa syndromes is highly
      heterogeneous with respect to organ involvement and severity. One of the major
      diagnostic criteria is to detect abnormal elastin fibers. In several other
      clinically similar autosomal recessive syndromes, however, the classic
      histological anomalies are absent, and the definite diagnosis remains uncertain.
      In cutis laxa patients mutations have been demonstrated in elastin or fibulin
      genes, but in the majority of patients the underlying genetic etiology remains
      unknown. Recently, we found mutations in the ATP6V0A2 gene in families with
      autosomal recessive cutis laxa. This genetic defect is associated with abnormal
      glycosylation leading to a distinct combined disorder of the biosynthesis of N-
      and O-linked glycans. Interestingly, similar mutations have been found in
      patients with wrinkly skin syndrome, without the presence of severe skin symptoms
      of elastin deficiency. These findings suggest that the cutis laxa and wrinkly
      skin syndromes are phenotypic variants of the same disorder. Interestingly many
      phenotypically similar patients carry no mutations in the ATP6V0A2 gene. The
      variable presence of protein glycosylation abnormalities in the diverse clinical
      forms of the wrinkled skin-cutis laxa syndrome spectrum necessitates revisiting
      the diagnostic criteria to be able to offer adequate prognosis assessment and
      counseling. This paper aims at describing the spectrum of clinical features of
      the various forms of autosomal recessive cutis laxa syndromes. Based on the
      recently unraveled novel genetic entity we also review the genetic aspects in
      cutis laxa syndromes including genotype-phenotype correlations and suggest a
      practical diagnostic approach.

PMID- 19401721
TI  - Tools available to communities for conducting cumulative exposure and risk
      assessments.
AB  - This paper summarizes and assesses over 70 tools that could aid with gathering
      information and taking action on environmental issues related to community-based
      cumulative risk assessments (CBCRA). Information on tool use, development and
      research needs, was gathered from websites, documents, and CBCRA program
      participants and researchers, including 25 project officers who work directly
      with community groups. The tools were assessed on the basis of information
      provided by project officers, community members, CBCRA researchers, and by case
      study applications. Tables summarize key environmental issues and tool features:
      (1) a listing of CBCRA-related environmental issues of concern to communities;
      (2) web-based tools that map environmental information; (3) step-by-step guidance
      documents; (4) databases of environmental information; and (5) computer models
      that simulate human exposure to chemical stressors. All tools described here are
      publicly available, with the focus being on tools developed by the US
      Environmental Protection Agency. These tables provide sources of information to
      promote risk identification and prioritization beyond risk perception approaches,
      and could be used by CBCRA participants and researchers. The purpose of this
      overview is twofold: (1) To present a comprehensive, though not exhaustive,
      summary of numerous tools that could aid with performing CBCRAs; and (2) To use
      this toolset as a sample of the current state of CBCRA tools to critically
      examine their utility and guide research for the development of new and improved
      tools.

PMID- 19401720
TI  - The role of mitochondrial genome in essential hypertension in a Chinese Han
      population.
AB  - Earlier genetic studies of essential hypertension have focused on nuclear genes
      or family-based mitochondrial screening in Caucasian and African-American
      pedigrees. The role of mitochondria in sporadic Chinese hypertensives is unknown.
      We sequenced mitochondrial genomes in 306 age- and gender-balanced Chinese Han
      hypertensives and controls. In 153 hypertensives, putative functional changes
      included 4 changes in rRNA genes, 11 changes in tRNA genes and 25 amino-acid
      substitutions. The remaining variants were synonymous changes or non-coding
      regions. In the 153 controls, 2 base changes in the tRNA genes and 13 amino-acid
      substitutions were found. A8701G in ATP6 gene (belongs to haplogroup M; P=0.0001)
      and C8414T in ATP8 gene (belongs to haplogroup D; P=0.01) were detected
      significantly different in the cases and controls. Interestingly, the cases were
      more likely to have two or more amino-acid changes and RNA variants compared with
      the controls (57.43 versus 23.81%, P=0.0001). In addition, several variants we
      found were highly conserved and/or specifically located at the 3' end adjacent to
      the anticodon, which may contribute to the stabilization of structure, and thus
      lead to the decrease of tRNA metabolism. In conclusion, mitochondrial SNPs
      (mtSNPs) may affect the course of hypertension in sporadic Chinese hypertensives.
      Some specific mtSNP within mitochondria may have potential role in the Chinese
      hypertensives due to their function. Synergetic interaction between mitochondrial
      mtSNPs and/or haplogroups is needed to be investigated in the future.

PMID- 19401722
TI  - Arsenic exposure in US public and domestic drinking water supplies: a comparative
      risk assessment.
AB  - Although approximately 35 million people in the US obtain drinking water from
      domestic wells, few studies have investigated the risk of arsenic exposure from
      this source. In this paper arsenic concentrations were modeled for public and
      domestic wells using a dataset from the US Geological Survey (USGS). Excess
      lifetime and annual risks for lung and bladder cancer were calculated based on
      the carcinogenic potency and average arsenic concentrations in public and
      domestic water supplies. Monte Carlo uncertainty analysis was used to estimate
      the degree of confidence in these estimations. Results indicated that domestic
      well users accounted for 12% of the US population, but 23% of overall arsenic
      exposure from drinking water. Assuming that the new and more restrictive arsenic
      maximum contaminant limit (MCL) is implemented for public water supplies, it is
      anticipated that the proportion of people experiencing excess annual fatalities
      from drinking water from domestic wells will increase to 29% unless corresponding
      efforts are made to reduce exposures among domestic well users. Differences
      between public and domestic wells were not consistent across the nation. Public
      wells tend to tap deeper aquifers than domestic wells, and as a result local
      arsenic-depth trends can contribute to differences between public and domestic
      wells. Domestic wells and public wells in the western US have the highest arsenic
      levels with excess fatality risks estimated to be in the range of 1 per 9300 to 1
      per 6600 in these regions. Uncertainty distributions of excess fatalities were
      developed and resultant uncertainties were propagated in arsenic exposure and
      potency factor. Uncertainty in the carcinogenic potency of arsenic was the
      dominant source of uncertainty in most regions, but for domestic wells in the New
      England and Southeast regions uncertainty in arsenic exposure was dominant,
      indicating that additional data on arsenic concentrations in these areas would
      substantially improve regional risk estimates.

PMID- 19401723
TI  - Effects of stress throughout the lifespan on the brain, behaviour and cognition.
AB  - Chronic exposure to stress hormones, whether it occurs during the prenatal
      period, infancy, childhood, adolescence, adulthood or aging, has an impact on
      brain structures involved in cognition and mental health. However, the specific
      effects on the brain, behaviour and cognition emerge as a function of the timing
      and the duration of the exposure, and some also depend on the interaction between
      gene effects and previous exposure to environmental adversity. Advances in animal
      and human studies have made it possible to synthesize these findings, and in this
      Review a model is developed to explain why different disorders emerge in
      individuals exposed to stress at different times in their lives.

PMID- 19401724
TI  - A 50 EW/cm;2 Ti:sapphire laser system for studying relativistic light-matter
      interactions.
AB  - A 10-Hz repetition rate, 60-TW peak power, Ti:sapphire laser system was developed
      for use in experiments where relativistic effects dominate the physics. The
      temporal, spectral, energy and spatial characteristics of the laser pulses were
      measured in single shot format. The pulse duration ranged from 22 fs to 25 fs and
      the pulse energy averaged 1.3 J. Atomic photoionization measurements quantified
      the peak intensity of the laser pulse in situ. The measurements indicated an
      intensity of at least 510 19 W/cm 2 was produced.

PMID- 19401725
TI  - Modeling of sensitivity and resolution to an included object in homogeneous
      scattering media and in MRI-derived breast maps.
AB  - We have examined the measured sensitivity and edge resolution to an included
      tumor in MR-derived maps of the breast exposed to NIR illumination. A large
      parameter space was explored, enabling a systematic examination of the influence
      that measurement parameters (e.g., view angle, source position, wavelength) and
      target medium parameters (e.g., breast and tumor size, background tissue
      properties, and tumor contrast) have on the computed responses. The significance
      of these finding on data collection schemes for imaging studies is discussed.

PMID- 19401726
TI  - Non-linear wave packet dynamics of coherent states of various symmetry groups.
AB  - We present a comparative study of the non-linear wave packet dynamics of two-mode
      coherent states of the Heisenberg-Weyl group, the SU(1,1) group and the SU(2)
      group under the action of a model anharmonic Hamiltonian. In each case, we find
      certain generic signatures of non-linear evolution such as quick onset of
      decoherence followed by Schrodinger cat formation and revival. We also report
      important differences in the evolution of coherent states belonging to different
      symmetry groups.

PMID- 19401727
TI  - Differential diffuse optical tomography.
AB  - We formulate a perturbative solution for the heterogeneous diffusion equation
      which demonstrates how to use differential changes in diffuse light transmission
      to construct images of tissue absorption changes following contrast agent
      administration. The analysis exposes approximations leading to an intuitive and
      simplified inverse algorithm, shows explicitly why transmission geometries are
      less susceptible to error than the remission geometries, and why differential
      measurements are less susceptible to surface artifacts. These ideas about
      differential diffuse optical tomography are not only applicable to tumor
      detection and characterization using contrast agents, but also to functional
      activation studies with or without contrast agents and multiple-wavelength
      measurements.

PMID- 19401728
TI  - 2D measurement and spatio-temporal coupling of few-cycle THz pulses.
AB  - The propagation of few-cycle THz pulses are measured by the improved CCD based 2D
      THz imaging system. There exists strong spatio-temporal shaping effect, leading
      to dramatically time dependent beam diameter and wave front. Theoretical
      simulation is given.

PMID- 19401729
TI  - Spatial correlation diagnostics for atoms in optical lattices.
AB  - We explore the use of first and second order same-time atomic spatial correlation
      functions as a diagnostic for probing the small scale spatial structure of atomic
      samples trapped in optical lattices. Assuming an ensemble of equivalent atoms,
      properties of the local wave function at a given lattice site can be measured
      using same-position first-order correlations. Statistics of atomic distributions
      over the lattice can be measured via two-point correlations, generally requiring
      the averaging of multiple realizations of statistically similar but distinct
      realizations in order to obtain sufficient signal to noise. Whereas two-point
      first order correlations are fragile due to phase fluctuations from shot-to-shot
      in the ensemble, second order correlations are robust. We perform numerical
      simulations to demonstrate these diagnostic tools.

PMID- 19401730
TI  - Fast and accurate low-coherence interferometric measurements of fiber Bragg
      grating dispersion and reflectance.
AB  - We demonstrate fast and accurate measurements of fiber Bragg grating dispersion
      and spectral reflectance using low-coherence interferometry. Both dispersion and
      spectral reflectance are obtained in less than 60 seconds, rendering the results
      immune to errors caused by temperature variations and instrumental drift. To
      examine the accuracy of the low-coherence technique, we compare the results with
      independent measurements and demonstrate an agreement better than 1.5 ps for
      dispersion and 25 pm for spectral reflectance wavelength.

PMID- 19401731
TI  - Simultaneous measurement of group delay and transmission of a one-dimensional
      photonic crystal.
AB  - We characterize both the group delay and the transmission of a layered
      semiconductor structure in a single easily interpreted plot. The data spans a 50
      nm wide spectral range with 1.7 nanometer wavelength resolution, and a 1.3
      picosecond wide temporal range with temporal resolution of tens of femtoseconds.
      Specific data for a 28 period GaAs/AlAs layered photonic band-gap structure that
      characterizes both group delay and transmission of multiple photonic resonances
      in a single display are presented and compared to theory.

PMID- 19401732
TI  - Optical parallel database management system for page oriented holographic
      memeories.
AB  - Current data recall rates from page oriented holographic memories far exceed the
      ability of electronics toeven read or transmit the data. For database management,
      we must not only read those data but also query them-computationally, a far more
      complex task. That task is very severe for electronics. We show here the
      rudiments of an optical system that can do most of the query operations in
      parallel in optics, leaving the burden for electronics significantly less. Even
      here, electronics is the ultimate speed limiter. Nevertheless, we can query data
      far faster in our optical/electronic system than any purely electronic system.

PMID- 19401733
TI  - Formation of dynamic cavity in a self-starting high-average-power Nd:YAG laser
      oscillator.
AB  - Self-organization of the dynamic cavity completed by holographic gratings in the
      novel laser oscillator was studied experimentally and numerically. A key role of
      the resonant grating of refractive index induced by generating beams in an Nd:YAG
      laser crystal was determined. Stabilization of the generated pulses and an
      increase in output power were achieved by use of a vibrating intracavity mirror.

PMID- 19401734
TI  - Optical amplifier for space applications.
AB  - We describe an optical amplifier designed to amplify a spatially sampled
      component of an optical wavefront to kilowatt average power. The goal is means
      for implementing a strategy of spatially segmenting a large aperture wavefront,
      amplifying the individual segments, maintaining the phase coherence of the
      segments by active means, and imaging the resultant amplified coherent field.
      Applications of interest are the transmission of space solar power over multi
      megameter distances, as to distant spacecraft, or to remote sites with no
      preexisting power grid.

PMID- 19401735
TI  - Reflectance spectroscopy with polarized light: is it sensitive to cellular and
      nuclear morphology.
AB  - We present a method for selective detection of size-dependent scattering
      characteristics of epithelial cells in vivo based on polarized illumination and
      polarization sensitive detection of scattered light. We illustrate the method
      using phantoms designed to simulate squamous epithelial tissue and progressing to
      epithelial tissue in vitro and in vivo. Elastic light scattering spectroscopy
      with polarized illumination/detection dramatically reduces background signals due
      to both diffuse stromal scattering and hemoglobin absorption. Resulting spectra
      can be described as a linear combination of forward and backscattering components
      determined from Mie theory. Nuclear sizes and refractive indices extracted by
      fitting experimental spectra to this model agree well with previous measurements.
      Reflectance spectroscopy with polarized light can provide quantitative
      morphological information which could potentially be used for non-invasive
      detection of neoplastic changes.

PMID- 19401736
TI  - All-solid-state 5-kHz 0.2-TW Ti:sapphire laser system.
AB  - We have developed an all-solid-state 5-kHz Ti:sapphire laser system, which
      produces 22-fs, 0.2-TW pulses. An average power of 22.2 W is the highest ever
      obtained in ultrashort laser sources. The serious thermal lensing due to high
      power pumping in a small area of the Ti:sapphire crystal is controlled
      successfully by a stable quasi-cavity with two concave mirrors.

PMID- 19401739
TI  - Editorial.
AB  - With this issue Optics Express begins Volume 6 of publication. We've been in
      business long enough that most OSA members, and a large fraction of the world
      wide optics community, are aware of Optics Express, even if many have not yet
      felt a strong push toward all-electronic peer-reviewed publishing. One reason for
      hesitation can be a natural concern for permanence of the scientific record, a
      concern about archiving. What is the assurance that articles published
      electronically will be openly available to scientists in the future?

PMID- 19401740
TI  - On the use of dual frequency nematic material for adaptive optics systems: first
      results of a closed-loop experiment.
AB  - The use of liquid crystal devices for wavefront control has been suggested and
      implemented by several authors. In this paper we report some preliminary results
      on the use of Nematic based liquid crystal devices. Several experimental efforts
      have been carried out in the past few months. One of the main aims was to
      characterize a new device that uses dual frequency nematic material in a closed
      loop arrangement.

PMID- 19401741
TI  - Possibility of fabricating light-emitting porous silicon from gas phase etchants.
AB  - We present a new technique for porous semiconductor formation which is based on
      the exposure of semiconductor surfaces to gas phase etchants. The technique
      offers the possibility of fabricating light-emitting devices by selectively
      exposing a silicon surface to HF vapor. Photoluminescence measurements reveal an
      efficient emission at around 750 nm. FTIR analysis confirm the existence of
      strong hydrogen incorporation and oxidation as evidenced from the local bonding
      environment of hydrogen and oxygen atoms.

PMID- 19401742
TI  - Propagation of ultrashort pulses in gaseous medium: breakdown of the quasistatic
      approximation.
AB  - We compare the results of the propagation of strong ultrashort laser pulse in gas
      medium where the atomic ionization is calculated in quasi-static approximation,
      and by using ab initio solution of the Schroedinger equation. Our models reveal
      significant difference between the predictions of the two models which may have
      an impact on the phase matched high-harmonic and attosecond pulse generation. A
      novel equation that avoids the concept of ionisation rate is introduced, which
      can be used to accurately model the generation and propagation of attosecond
      duration pulses.

PMID- 19401743
TI  - Near real time confocal microscopy of amelanotic tissue: dynamics of aceto
      whitening enable nuclear segmentation.
AB  - High resolution, in vivo confocal imaging of amelanotic epithelial tissue may
      offer a clinically useful adjunct to standard histopathologic techniques.
      Application of acetic acid has been shown to enhance contrast in confocal images
      of these tissues. In this study, we record the time course of aceto-whitening at
      the cellular level and determine whether the contrast provided enables
      quantitative feature analysis. Confocal images and videos of cervical specimens
      were obtained throughout the epithelium before, during and post-acetic acid after
      the application of 6% acetic acid. Aceto-whitening occurs within seconds after
      the application. The confocal imaging system resolved sub-cellular detail
      throughout the entire epithelial thickness and provided sufficient contrast to
      enable quantitative feature analysis.

PMID- 19401744
TI  - On-line optical imaging of the human brain with 160-ms temporal resolution.
AB  - We have developed an instrument for non-invasive optical imaging of the human
      brain that produces on-line images with a temporal resolution of 160 ms. The
      imaged quantities are the temporal changes in cerebral oxy-hemoglobin and deoxy
      hemoglobin concentrations. We report real-time videos of the arterial pulsation
      and motor activation recorded on a 4 x 9 cm 2 area of the cerebral cortex in a
      healthy human subject. This approach to optical brain imaging is a powerful tool
      for the investigation of the spatial and temporal features of the optical signals
      collected on the brain.

PMID- 19401745
TI  - Continuous-wave, singly-resonant, optical parametric oscillator based on
      periodically poled KTiOPO4.
AB  - A continuous-wave singly-resonant optical parametric oscillator (SRO) has been
      implemented using a 20 mm long crystal of periodically poled KTiOPO 4 (PPKTP)
      intracavity-pumped at room temperature within a Ti:sapphire laser. The device
      delivers a maximum output power of 455 mW at a non-resonant idler wavelength of
      2.47 microm. The 28.5-microm grating PPKTP crystal provides SRO tuning over 1.14
      1.27 microm (signal) and 2.23-2.73 microm (idler) limited by optical coating
      bandwidths and corresponding to a pump tuning range of 805.5-811.2 nm.
      Temperature tuning of the device generated signal and idler ranges of 1.18-1.26
      microm and 2.29-2.57 microm, respectively, corresponding to an average tuning
      rate of 1.2 nm/degree (signal) and 4.5 nm/degree (idler). Ring-cavity
      configuration of the device resulted in generation of 115 mW of single-frequency
      idler output at 2.35 microm.

PMID- 19401747
TI  - All-optical binary counter.
AB  - We experimentally demonstrate an all-optical binary counter composed of four
      semiconductor optical amplifier based all-optical switching gates. The time-of
      flight optical circuit operates with bit-differential delays between the
      exclusive-OR gate used for modulo-2 binary addition and the AND gate used for
      binary carry detection. A movie of the counter operating in real time is
      presented.

PMID- 19401746
TI  - Two-photon holography in a 3D photopolymer host-guest matrix.
AB  - We demonstrate for the first time two-photon induced holographic recording at an
      arbitrary point in three dimensional photopolymeric cube by overlapping two
      coherent pulses from a 200 femtosecond Ti: Sapphire tunable laser operating at
      710 nm. Spatial overlap is achieved by a novel pupil division method. The polymer
      material is made of epoxy host, which is fully polymerized and filled with liquid
      photopolymerisable formulation comprising acrylate type monomer and two-photon
      photoinitiator. Measured diffraction efficiency is measured to be 3.5%.

PMID- 19401748
TI  - Robust optical control of an optical-amplifier-based flip-flop.
AB  - We demonstrate new optical techniques for externally controlling the latchable
      output power of a semiconductor-optical-amplifier-based flip-flop. Optical 'set'
      and 'reset' signals increase and decrease the re-fractive index, respectively,
      via cross-phase modulation (XPM). Set signals, which deplete the carrier density,
      have wavelengths between 1533 and 1568 nm, and powers as low as 22 microW. Reset
      is performed with carrier-generating 'positive' optical pulses at 1306 and 1466
      nm, and minimum powers below 1 mW. These techniques are useful for digital
      optical-processing functions such as bit-length conversion, retiming, and
      demultiplexing.

PMID- 19401749
TI  - Real-time gas-correlation imaging employing thermal background radiation.
AB  - Real-time imaging of gas leaks was demonstrated using an IR camera employing
      outdoor thermal background radiation. Ammonia, ethylene and methane detection was
      demonstrated in the spectral region 7-13 microm. Imaging was accomplished using
      an optical filter and a gas-correlation cell matching the absorption band of the
      gas. When two gases, such as ammonia and ethylene, are absorbing in the same
      wavelength region it is possible to isolate one for display by using gas
      correlation multispectral imaging. Results from a field test on a leaking gas
      tanker are presented as QuickTime movies. A detection limit of 200 ppm x meter
      for ammonia was accomplished in this setup when the temperature difference
      between the background and the gas was 18 K and the frame rate was 15 Hz.

PMID- 19401750
TI  - Optical properties of Nd doped Bi2O3-PbO-Ga2O3 glasses.
AB  - The optical properties of a new family of neodymium doped BPG (Bi2O3-PbO-Ga2O3 )
      glasses are presented. We measured a high refractive index, of 2.5, and a
      transmission cutoff in the far infrared at 8microm. Three intense emission bands
      are observed centered at 877nm, 1066nm and 1341nm. The emission cross-section is
      10 -20 cm 2 and the total spectral linewidth is 30nm at 1066nm. The Judd-Ofelt
      parameters are calculated and used to evaluate transition probability, radiative
      lifetime and branching ratios. The optical properties of these Nd:BPG glasses
      show promise for their use as a new active laser material.

PMID- 19401751
TI  - Two-photon holography in 3-D photopolymer host-guest matrix: errata.
AB  - : Correction to References. Commercial codes of the chemicals are added.

PMID- 19401752
TI  - Double ionization in a one-cycle laser pulse.
AB  - The time-dependent Schrodinger equation is solved for a 1Dx1D two-electron model
      helium atom subject to a low-frequency short, intense laser pulse. A half-cycle
      pulse leads to strong single but no double ionization. A full-cycle pulse leads
      to double ionization which begins precisely at the classical return time for the
      first ejected electron. When the excursion range for the first electron is
      truncated, the double ionization at later times, corresponding to longer
      excursions, disappears. When the field near the nucleus is turned off during the
      return of the first electron, double ionization persists.

PMID- 19401753
TI  - Coherent control of strong-field two-pulse ionization of Rydberg atoms.
AB  - Strong-field ionization of Rydberg atoms is investigated in its dependence on
      phase features of the initial coherent population of Rydberg levels. In the case
      of a resonance between Rydberg levels and some lower-energy atomic level (V-type
      transitions), this dependence is shown to be very strong: by a proper choice of
      the initial population an atom can be made either completely or very little
      ionized by a strong laser pulse. It is shown that phase features of the initial
      coherent population of Rydberg levels and the ionization yield can be efficiently
      controlled in a scheme of ionization by two strong laser pulses with a varying
      delay time between them.

PMID- 19401754
TI  - Analysis of optical-signal processing using an arrayed-waveguide grating.
AB  - We analyzed optical signal processing based on time-space conversion in an
      arrayed-waveguide grating (AWG). General expressions for the electric fields
      needed to design frequency filters were obtained. We took into account the
      effects of the waveguides and clearly distinguished the temporal frequency axis
      from the spatial axis at the focal plane where the frequency filters were placed.
      Using the analytical results, we clarified what limits the input pulse width as
      well as the windowing effect, the effect of phase fluctuation in the arrayed
      waveguide.

PMID- 19401755
TI  - Contact networks in a wildlife-livestock host community: identifying high-risk
      individuals in the transmission of bovine TB among badgers and cattle.
AB  - BACKGROUND: The management of many pathogens, which are of concern to humans and
      their livestock, is complicated by the pathogens' ability to cross-infect
      multiple host species, including wildlife. This has major implications for the
      management of such diseases, since the dynamics of infection are dependent on the
      rates of both intra- and inter-specific transmission. However, the difficulty of
      studying transmission networks in free-living populations means that the relative
      opportunities for intra- versus inter-specific disease transmission have not
      previously been demonstrated empirically within any wildlife-livestock disease
      system. METHODOLOGY/PRINCIPAL FINDINGS: Using recently-developed proximity data
      loggers, we quantify both intra- and inter-specific contacts in a wildlife
      livestock disease system, using bovine tuberculosis (bTB) in badgers and cattle
      in the UK as our example. We assess the connectedness of individuals within the
      networks in order to identify whether there are certain 'high-risk' individuals
      or groups of individuals for disease transmission within and between species. Our
      results show that contact patterns in both badger and cattle populations vary
      widely, both between individuals and over time. We recorded only infrequent
      interactions between badger social groups, although all badgers fitted with data
      loggers were involved in these inter-group contacts. Contacts between badgers and
      cattle occurred more frequently than contacts between different badger groups.
      Moreover, these inter-specific contacts involved those individual cows, which
      were highly connected within the cattle herd. CONCLUSIONS/SIGNIFICANCE: This work
      represents the first continuous time record of wildlife-host contacts for any
      free-living wildlife-livestock disease system. The results highlight the
      existence of specific individuals with relatively high contact rates in both
      livestock and wildlife populations, which have the potential to act as hubs in
      the spread of disease through complex contact networks. Targeting testing or
      preventive measures at high-contact groups and individuals within livestock
      populations would enhance the effectiveness and efficiency of disease management
      strategies.

PMID- 19401756
TI  - Protein domain boundary predictions: a structural biology perspective.
AB  - One of the important fields to apply computational tools for domain boundaries
      prediction is structural biology. They can be used to design protein constructs
      that must be expressed in a stable and functional form and must produce
      diffraction-quality crystals. However, prediction of protein domain boundaries on
      the basis of amino acid sequences is still very problematical. In present study
      the performance of several computational approaches are compared. It is observed
      that the statistical significance of most of the predictions is rather poor.
      Nevertheless, when the right number of domains is correctly predicted, domain
      boundaries are predicted within very few residues from their real location. It
      can be concluded that prediction methods cannot be used yet as routine tools in
      structural biology, though some of them are rather promising.

PMID- 19401757
TI  - Calcium-induced conformational transition of trout ependymins monitored by
      tryptophan fluorescence.
AB  - Ependymins are secretory, calcium-binding sialoproteins which are the predominant
      constituents of the cerebrospinal fluid of many teleost fish. A bound form of
      these regeneration-responsive glycoproteins is associated with collagen fibrils
      of the extracellular matrix. Here, the tryptophan fluorescence of ependymins was
      monitored at various Ca(2+) concentrations. Two distinct states were identified
      with a relatively sharp transition at about 1 mM Ca(2+). In agreement with
      previous circular dichroism measurements, this strongly supports the hypothesis
      that a calcium-induced conformational change is important for the interaction of
      ependymins with components of the extracellular matrix. Such interactions with
      constituents of various basal laminae would also explain the important roles of
      piscine ependymins as well as invertebrate and mammalian ependymin-related
      proteins for cell adhesion processes and cell migration.

PMID- 19401758
TI  - Persistent diet-induced obesity in male C57BL/6 mice resulting from temporary
      obesigenic diets.
AB  - BACKGROUND: Does diet-induced obesity persist after an obesigenic diet is
      removed? We investigated this question by providing male C57BL/6 mice with free
      access to two different obesigenic diets followed by a switch to chow to
      determine if obesity was reversible. METHODOLOGY/PRINCIPAL FINDINGS: Male C57BL/6
      mice were randomly assigned to five weight-matched groups: 1) C group that
      continuously received a chow diet; 2) HF group on a 60% high fat diet; 3) EN
      group on the high fat diet plus liquid Ensure; 4) HF-C group switched from high
      fat to chow after 7 weeks; 5) EN-C group switched from high fat plus Ensure to
      chow after 7 weeks. All food intake was ad libitum. Body weight was increased
      after 7 weeks on both obesigenic diets (44.6+/-0.65, 39.8+/-0.63, and 28.6+/-0.63
      g for EN, HF, and C groups, respectively) and resulted in elevated concentrations
      of serum insulin, glucose, and leptin and lower serum triglycerides. Development
      of obesity in HF and EN mice was caused by increased energy intake and a relative
      decrease of average energy output along with decreased ambulatory activity. After
      the switch to chow, the HF-C and EN-C groups lost weight but subsequently
      maintained a state of persistent obesity in comparison to the C group (34.8+/
      1.2, 34.1+/-1.2 vs. 30.8+/-0.8 g respectively; P<0.05) with a 40-50% increase of
      body fat. All serum hormones and metabolites returned to control levels with the
      exception of a trend for increased leptin. The HF-C and EN-C groups had an
      average energy output in line with the C group and the persistent obesity was
      maintained despite a non-significant increase of energy intake of less than 1
      kcal/d at the end of the study. CONCLUSION: Our results illustrate the importance
      of considering the history of energy imbalance in determining body weight and
      that a persistent elevation of body weight after removal of obesigenic diets can
      result from very small increases of energy intake.

PMID- 19401760
TI  - Distribution and extinction of ungulates during the Holocene of the southern
      Levant.
AB  - BACKGROUND: The southern Levant (Israel, Palestinian Authority and Jordan) has
      been continuously and extensively populated by succeeding phases of human
      cultures for the past 15,000 years. The long human impact on the ancient
      landscape has had great ecological consequences, and has caused continuous and
      accelerating damage to the natural environment. The rich zooarchaeological data
      gathered at the area provide a unique opportunity to reconstruct spatial and
      temporal changes in wild species distribution, and correlate them with human
      demographic changes. METHODOLOGY: Zoo-archaeological data (382 animal bone
      assemblages from 190 archaeological sites) from various time periods, habitats
      and landscapes were compared. The bone assemblages were sorted into 12 major
      cultural periods. Distribution maps showing the presence of each ungulate species
      were established for each period. CONCLUSIONS: The first major ungulate
      extinction occurred during the local Iron Age (1,200-586 BCE), a period
      characterized by significant human population growth. During that time the last
      of the largest wild ungulates, the hartebeest (Alcelaphus buselaphus), aurochs
      (Bos primigenius) and the hippopotamus (Hippopotamus amphibius) became extinct,
      followed by a shrinking distribution of forest-dwelling cervids. A second major
      wave of extinction occurred only in the 19th and 20th centuries CE. Furthermore,
      a negative relationship was found between the average body mass of ungulate
      species that became extinct during the Holocene and their extinction date. It is
      thus very likely that the intensified human activity through habitat destruction
      and uncontrolled hunting were responsible for the two major waves of ungulate
      extinction in the southern Levant during the late Holocene.

PMID- 19401759
TI  - Alternate splicing of interleukin-1 receptor type II (IL1R2) in vitro correlates
      with clinical glucocorticoid responsiveness in patients with AIED.
AB  - Autoimmune Inner Ear Disease (AIED) is poorly characterized clinically, with no
      definitive laboratory test. All patients suspected of having AIED are given
      glucocorticoids during periods of acute hearing loss, however, only half
      initially respond, and still fewer respond over time.We hypothesized that AIED is
      a systemic autoimmune disease characterized by dysfunctional peripheral blood
      mononuclear cells (PBMC) responses to a unique cochlear antigen(s). To test this
      hypothesis, we examined end-stage AIED patients undergoing cochlear implant
      surgery and compared autologous perilymph stimulated PBMC from AIED patients to
      controls. We determined that autologous perilymph from AIED patients was unable
      to induce expression of a long membrane-bound Interleukin-1 Receptor Type II
      (mIL1R2) transcript in PBMC as compared with controls, despite similar expression
      of the short soluble IL1R2 (sIL1R2) transcript (p<0.05). IL1R2 is a molecular
      decoy that traps interleukin-1beta (IL-1beta) and does not initiate subsequent
      signaling events, thereby suppressing an inflammatory response. IL1R2 transcript
      length is regulated by alternate splicing, and the major inhibitory function is
      attributed to the full-length mIL1R2. In addition, IL1R2 expression is induced by
      dexamethasone.Separately, we prospectively examined patients with newer onset
      glucocorticoid-responsive AIED. Immediately prior to clinical treatment for acute
      deterioration of hearing thresholds, their PBMC demonstrated a robust induction
      of mIL1R2 in PBMC in response to dexamethasone in vitro that correlated with a
      clinical response to prednisone in vivo (p<0.0001) as measured by hearing
      restoration. In contrast, clinically steroid unresponsive patients demonstrated
      high basal levels of mIL1R2 in their PBMC and only minimally augmented expression
      in response to dexamethasone. Thus, induced expression of mIL1R2 appears to be a
      protective mechanism in hearing homeostasis and warrants further investigation in
      a large prospective clinical trial to determine if IL1R2 can be used as a
      specific biomarker for AIED.

PMID- 19401762
TI  - Modeling statistical properties of written text.
AB  - Written text is one of the fundamental manifestations of human language, and the
      study of its universal regularities can give clues about how our brains process
      information and how we, as a society, organize and share it. Among these
      regularities, only Zipf's law has been explored in depth. Other basic properties,
      such as the existence of bursts of rare words in specific documents, have only
      been studied independently of each other and mainly by descriptive models. As a
      consequence, there is a lack of understanding of linguistic processes as complex
      emergent phenomena. Beyond Zipf's law for word frequencies, here we focus on
      burstiness, Heaps' law describing the sublinear growth of vocabulary size with
      the length of a document, and the topicality of document collections, which
      encode correlations within and across documents absent in random null models. We
      introduce and validate a generative model that explains the simultaneous
      emergence of all these patterns from simple rules. As a result, we find a
      connection between the bursty nature of rare words and the topical organization
      of texts and identify dynamic word ranking and memory across documents as key
      mechanisms explaining the non trivial organization of written text. Our research
      can have broad implications and practical applications in computer science,
      cognitive science and linguistics.

PMID- 19401761
TI  - Distinct mechanisms underlying tolerance to intermittent and constant hypoxia in
      Drosophila melanogaster.
AB  - BACKGROUND: Constant hypoxia (CH) and intermittent hypoxia (IH) occur during
      several pathological conditions such as asthma and obstructive sleep apnea. Our
      research is focused on understanding the molecular mechanisms that lead to injury
      or adaptation to hypoxic stress using Drosophila as a model system. Our current
      genome-wide study is designed to investigate gene expression changes and identify
      protective mechanism(s) in D. melanogaster after exposure to severe (1% O(2))
      intermittent or constant hypoxia. METHODOLOGY/PRINCIPAL FINDINGS: Our microarray
      analysis has identified multiple gene families that are up- or down-regulated in
      response to acute CH or IH. We observed distinct responses to IH and CH in gene
      expression that varied in the number of genes and type of gene families. We then
      studied the role of candidate genes (up-or down-regulated) in hypoxia tolerance
      (adult survival) for longer periods (CH-7 days, IH-10 days) under severe CH or
      IH. Heat shock proteins up-regulation (specifically Hsp23 and Hsp70) led to a
      significant increase in adult survival (as compared to controls) of P-element
      lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and
      l(2)08717 genes (P-element lines) provided survival advantage over controls. This
      suggests that the increased transcript levels following treatment with either
      paradigm play an important role in tolerance to severe hypoxia. Furthermore, by
      over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70
      in heart and brain play critical role in tolerance to CH in flies.
      CONCLUSIONS/SIGNIFICANCE: We observed that the gene expression response to IH or
      CH is specific and paradigm-dependent. We have identified several genes Hsp23,
      Hsp70, CG1600, l(2)08717 and Mdr49 that play an important role in hypoxia
      tolerance whether it is in CH or IH. These data provide further clues about the
      mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and
      survival.

PMID- 19401763
TI  - Conservation and variability of West Nile virus proteins.
AB  - West Nile virus (WNV) has emerged globally as an increasingly important pathogen
      for humans and domestic animals. Studies of the evolutionary diversity of the
      virus over its known history will help to elucidate conserved sites, and
      characterize their correspondence to other pathogens and their relevance to the
      immune system. We describe a large-scale analysis of the entire WNV proteome,
      aimed at identifying and characterizing evolutionarily conserved amino acid
      sequences. This study, which used 2,746 WNV protein sequences collected from the
      NCBI GenPept database, focused on analysis of peptides of length 9 amino acids or
      more, which are immunologically relevant as potential T-cell epitopes. Entropy
      based analysis of the diversity of WNV sequences, revealed the presence of
      numerous evolutionarily stable nonamer positions across the proteome (entropy
      value of < or = 1). The representation (frequency) of nonamers variant to the
      predominant peptide at these stable positions was, generally, low (< or = 10% of
      the WNV sequences analyzed). Eighty-eight fragments of length 9-29 amino acids,
      representing approximately 34% of the WNV polyprotein length, were identified to
      be identical and evolutionarily stable in all analyzed WNV sequences. Of the 88
      completely conserved sequences, 67 are also present in other flaviviruses, and
      several have been associated with the functional and structural properties of
      viral proteins. Immunoinformatic analysis revealed that the majority (78/88) of
      conserved sequences are potentially immunogenic, while 44 contained
      experimentally confirmed human T-cell epitopes. This study identified a
      comprehensive catalogue of completely conserved WNV sequences, many of which are
      shared by other flaviviruses, and majority are potential epitopes. The complete
      conservation of these immunologically relevant sequences through the entire
      recorded WNV history suggests they will be valuable as components of peptide
      specific vaccines or other therapeutic applications, for sequence-specific
      diagnosis of a wide-range of Flavivirus infections, and for studies of homologous
      sequences among other flaviviruses.

PMID- 19401764
TI  - Comparative proteomics analyses reveal the virB of B. melitensis affects
      expression of intracellular survival related proteins.
AB  - BACKGROUND: Brucella melitensis is a facultative, intracellular, pathogenic
      bacterium that replicates within macrophages. The type IV secretion system
      encoded by the virB operon (virB) is involved in Brucella intracellular survival.
      However, the underlying molecular mechanisms, especially the target proteins
      affected by the virB, remain largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: In
      order to define the proteins affected by virB, the proteomes of wild-type and the
      virB mutant were compared under in vitro conditions where virB was highly
      activated. The differentially expressed proteins were identified by MALDI-TOF-MS.
      Forty-four down-regulated and eighteen up-regulated proteins which exhibited a 2
      fold or greater change were identified. These proteins included those involved in
      amino acid transport and metabolism, lipid metabolism, energy production, cell
      membrane biogenesis, translation, post-translational modifications and protein
      turnover, as well as unknown proteins. Interestingly, several important virulence
      related proteins involved in intracellular survival, including VjbR, DnaK, HtrA,
      Omp25, and GntR, were down-regulated in the virB mutant. Transcription analysis
      of virB and vjbR at different growth phase showed that virB positively affect
      transcription of vjbR in a growth phase dependent manner. Quantitative RT-PCR
      showed that transcription of these genes was also affected by virB during
      macrophage cell infection, consistent with the observed decreased survival of the
      virB mutant in macrophage. CONCLUSIONS/SIGNIFICANCE: These data indicated that
      the virB operon may control the intracellular survival of Brucella by affecting
      the expression of relevant proteins.

PMID- 19401765
TI  - Peptide Bbeta(15-42) preserves endothelial barrier function in shock.
AB  - Loss of vascular barrier function causes leak of fluid and proteins into tissues,
      extensive leak leads to shock and death. Barriers are largely formed by
      endothelial cell-cell contacts built up by VE-cadherin and are under the control
      of RhoGTPases. Here we show that a natural plasmin digest product of fibrin,
      peptide Bbeta15-42 (also called FX06), significantly reduces vascular leak and
      mortality in animal models for Dengue shock syndrome. The ability of Bbeta15-42
      to preserve endothelial barriers is confirmed in rats i.v.-injected with LPS. In
      endothelial cells, Bbeta15-42 prevents thrombin-induced stress fiber formation,
      myosin light chain phosphorylation and RhoA activation. The molecular key for the
      protective effect of Bbeta15-42 is the src kinase Fyn, which associates with VE
      cadherin-containing junctions. Following exposure to Bbeta15-42 Fyn dissociates
      from VE-cadherin and associates with p190RhoGAP, a known antagonists of RhoA
      activation. The role of Fyn in transducing effects of Bbeta15-42 is confirmed in
      Fyn(-/-) mice, where the peptide is unable to reduce LPS-induced lung edema,
      whereas in wild type littermates the peptide significantly reduces leak. Our
      results demonstrate a novel function for Bbeta15-42. Formerly mainly considered
      as a degradation product occurring after fibrin inactivation, it has now to be
      considered as a signaling molecule. It stabilizes endothelial barriers and thus
      could be an attractive adjuvant in the treatment of shock.

PMID- 19401767
TI  - Scaling of soaring seabirds and implications for flight abilities of giant
      pterosaurs.
AB  - The flight ability of animals is restricted by the scaling effects imposed by
      physical and physiological factors. In comparisons of the power available from
      muscle and the mechanical power required to fly, it is predicted that the margin
      between the powers should decrease with body size and that flying animals have a
      maximum body size. However, predicting the absolute value of this upper limit has
      proven difficult because wing morphology and flight styles varies among species.
      Albatrosses and petrels have long, narrow, aerodynamically efficient wings and
      are considered soaring birds. Here, using animal-borne accelerometers, we show
      that soaring seabirds have two modes of flapping frequencies under natural
      conditions: vigorous flapping during takeoff and sporadic flapping during
      cruising flight. In these species, high and low flapping frequencies were found
      to scale with body mass (mass(-0.30) and mass(-0.18)) in a manner similar to the
      predictions from biomechanical flight models (mass(-1/3) and mass(-1/6)). These
      scaling relationships predicted that the maximum limits on the body size of
      soaring animals are a body mass of 41 kg and a wingspan of 5.1 m. Albatross-like
      animals larger than the limit will not be able to flap fast enough to stay aloft
      under unfavourable wind conditions. Our result therefore casts doubt on the
      flying ability of large, extinct pterosaurs. The largest extant soarer, the
      wandering albatross, weighs about 12 kg, which might be a pragmatic limit to
      maintain a safety margin for sustainable flight and to survive in a variable
      environment.

PMID- 19401766
TI  - Non-canonical Wnt signaling and N-cadherin related beta-catenin signaling play a
      role in mechanically induced osteogenic cell fate.
AB  - BACKGROUND: Understanding how the mechanical microenvironment influences cell
      fate, and more importantly, by what molecular mechanisms, will enhance not only
      the knowledge of mesenchymal stem cell biology but also the field of regenerative
      medicine. Mechanical stimuli, specifically loading induced oscillatory fluid
      flow, plays a vital role in promoting healthy bone development, homeostasis and
      morphology. Recent studies suggest that such loading induced fluid flow has the
      potential to regulate osteogenic differentiation via the upregulation of multiple
      osteogenic genes; however, the molecular mechanisms involved in the transduction
      of a physical signal into altered cell fate have yet to be determined. METHODS
      AND PRINCIPAL FINDINGS: Using immuno-staining, western blot analysis and
      luciferase assays, we demonstrate the oscillatory fluid flow regulates beta
      catenin nuclear translocation and gene transcription. Additionally, real time RT
      PCR analysis suggests that flow induces Wnt5a and Ror2 upregulation, both of
      which are essential for activating the small GTPase, RhoA, upon flow exposure.
      Furthermore, although beta-catenin phosphorylation is not altered by flow, its
      association with N-cadherin is, indicating that flow-induced beta-catenin
      signaling is initiated by adherens junction signaling. CONCLUSION: We propose
      that the mechanical microenvironment of bone has the potential to regulate
      osteogenic differentiation by initiating multiple key molecular pathways that are
      essential for such lineage commitment. Specifically, non-canonical Wnt5a
      signaling involving Ror2 and RhoA as well as N-cadherin mediated beta-catenin
      signaling are necessary for mechanically induced osteogenic differentiation.

PMID- 19401768
TI  - In vivo tumor targeting and imaging with engineered trivalent antibody fragments
      containing collagen-derived sequences.
AB  - There is an urgent need to develop new and effective agents for cancer targeting.
      In this work, a multivalent antibody is characterized in vivo in living animals.
      The antibody, termed "trimerbody", comprises a single-chain antibody (scFv)
      fragment connected to the N-terminal trimerization subdomain of collagen XVIII
      NC1 by a flexible linker. As indicated by computer graphic modeling, the
      trimerbody has a tripod-shaped structure with three highly flexible scFv heads
      radially outward oriented. Trimerbodies are trimeric in solution and exhibited
      multivalent binding, which provides them with at least a 100-fold increase in
      functional affinity than the monovalent scFv. Our results also demonstrate the
      feasibility of producing functional bispecific trimerbodies, which concurrently
      bind two different ligands. A trimerbody specific for the carcinoembryonic
      antigen (CEA), a classic tumor-associated antigen, showed efficient tumor
      targeting after systemic administration in mice bearing CEA-positive tumors.
      Importantly, a trimerbody that recognizes an angiogenesis-associated laminin
      epitope, showed excellent tumor localization in several cancer types, including
      fibrosarcomas and carcinomas. These results illustrate the potential of this new
      antibody format for imaging and therapeutic applications, and suggest that some
      laminin epitopes might be universal targets for cancer targeting.

PMID- 19401769
TI  - Range expansion drives dispersal evolution in an equatorial three-species
      symbiosis.
AB  - BACKGROUND: Recurrent climatic oscillations have produced dramatic changes in
      species distributions. This process has been proposed to be a major evolutionary
      force, shaping many life history traits of species, and to govern global patterns
      of biodiversity at different scales. During range expansions selection may favor
      the evolution of higher dispersal, and symbiotic interactions may be affected. It
      has been argued that a weakness of climate fluctuation-driven range dynamics at
      equatorial latitudes has facilitated the persistence there of more specialized
      species and interactions. However, how much the biology and ecology of species is
      changed by range dynamics has seldom been investigated, particularly in
      equatorial regions. METHODOLOGY/PRINCIPAL FINDINGS: We studied a three-species
      symbiosis endemic to coastal equatorial rainforests in Cameroon, where the impact
      of range dynamics is supposed to be limited, comprised of two species-specific
      obligate mutualists--an ant-plant and its protective ant--and a species-specific
      ant parasite of this mutualism. We combined analyses of within-species genetic
      diversity and of phenotypic variation in a transect at the southern range limit
      of this ant-plant system. All three species present congruent genetic signatures
      of recent gradual southward expansion, a result compatible with available
      regional paleoclimatic data. As predicted, this expansion has been accompanied by
      the evolution of more dispersive traits in the two ant species. In contrast, we
      detected no evidence of change in lifetime reproductive strategy in the tree, nor
      in its investment in food resources provided to its symbiotic ants.
      CONCLUSIONS/SIGNIFICANCE: Despite the decreasing investment in protective workers
      and the increasing investment in dispersing females by both the mutualistic and
      the parasitic ant species, there was no evidence of destabilization of the
      symbiosis at the colonization front. To our knowledge, we provide here the first
      evidence at equatorial latitudes that biological traits associated with dispersal
      are affected by the range expansion dynamics of a set of interacting species.

PMID- 19401770
TI  - Genetic determinants of facial clefting: analysis of 357 candidate genes using
      two national cleft studies from Scandinavia.
AB  - BACKGROUND: Facial clefts are common birth defects with a strong genetic
      component. To identify fetal genetic risk factors for clefting, 1536 SNPs in 357
      candidate genes were genotyped in two population-based samples from Scandinavia
      (Norway: 562 case-parent and 592 control-parent triads; Denmark: 235 case-parent
      triads). METHODOLOGY/PRINCIPAL FINDINGS: We used two complementary statistical
      methods, TRIMM and HAPLIN, to look for associations across these two national
      samples. TRIMM tests for association in each gene by using multi-SNP genotypes
      from case-parent triads directly without the need to infer haplotypes. HAPLIN on
      the other hand estimates the full haplotype distribution over a set of SNPs and
      estimates relative risks associated with each haplotype. For isolated cleft lip
      with or without cleft palate (I-CL/P), TRIMM and HAPLIN both identified
      significant associations with IRF6 and ADH1C in both populations, but only HAPLIN
      found an association with FGF12. For isolated cleft palate (I-CP), TRIMM found
      associations with ALX3, MKX, and PDGFC in both populations, but only the
      association with PDGFC was identified by HAPLIN. In addition, HAPLIN identified
      an association with ETV5 that was not detected by TRIMM. CONCLUSION/SIGNIFICANCE:
      Strong associations with seven genes were replicated in the Scandinavian samples
      and our approach effectively replicated the strongest previously known
      association in clefting--with IRF6. Based on two national cleft cohorts of
      similar ancestry, two robust statistical methods and a large panel of SNPs in the
      most promising cleft candidate genes to date, this study identified a previously
      unknown association with clefting for ADH1C and provides additional candidates
      and analytic approaches to advance the field.

PMID- 19401771
TI  - Motor decline in clinically presymptomatic spinocerebellar ataxia type 2 gene
      carriers.
AB  - BACKGROUND: Motor deficits are a critical component of the clinical
      characteristics of patients with spinocerebellar ataxia type 2. However, there is
      no current information on the preclinical manifestation of those motor deficits
      in presymptomatic gene carriers. To further understand and characterize the onset
      of the clinical manifestation in this disease, we tested presymptomatic
      spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that
      evaluates their motor performance and their motor learning capabilities. METHODS
      AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and
      an equal number of control volunteers matched for age and gender participated in
      the study. Both groups were tested in a prism adaptation task known to be
      sensible to both motor performance and visuomotor learning deficits. Our results
      clearly show that although motor learning capabilities are intact, motor
      performance deficits are present even years before the clinical manifestation of
      the disease start. CONCLUSIONS: The results show a clear deficit in motor
      performance that can be detected years before the clinical onset of the disease.
      This motor performance deficit appears before any motor learning or clinical
      manifestations of the disease. These observations identify the performance
      coefficient as an objective and quantitative physiological biomarker that could
      be useful to assess the efficiency of different therapeutic agents.

PMID- 19401773
TI  - Stoichiometric constraints do not limit successful invaders: zebra mussels in
      Swedish lakes.
AB  - BACKGROUND: Elemental imbalances of carbon (C): nitrogen (N): phosphorus (P)
      ratios in food resources can constrain the growth of grazers owning to tight
      coupling between growth rate, RNA allocation and biomass P content in animals.
      Testing for stoichiometric constraints among invasive species is a novel
      challenge in invasion ecology to unravel how a successful invader tackles
      ecological barriers in novel ecosystems. METHODOLOGY/PRINCIPAL FINDINGS: We
      examined the C:P and N:P ratios and the condition factor of a successful invader
      in lakes, the zebra mussel (Dreissena polymorpha), collected from two Swedish
      lakes. Concurrently, we analyzed the elemental composition of the food (seston)
      and tissue of the mussels in which nutrient composition of food and mussels
      varied over time. Zebra mussel condition factor was weakly related to the their
      own tissue N:P and C:P ratios, although the relation with the later ratio was not
      significant. Smaller mussels had relatively lower tissue N:P ratio and higher
      condition factor. There was no difference in C:P and N:P ratios between seston
      and mussels' tissues. Our results indicated that the variation in nutrient
      stoichiometry of zebra mussels can be explained by food quality and quantity.
      CONCLUSIONS/SIGNIFICANCE: Our study suggests that fitness of invasive zebra
      mussels is not constrained by nutrient stoichiometry which is likely to be
      important for their proliferation in novel ecosystems. The lack of imbalance in
      C:P and N:P ratios between seston and mussels along with high tissue C:P ratio of
      the mussel allow them to tolerate potential P limitation and maintain high growth
      rate. Moreover, zebra mussels are able to change their tissue C:P and N:P ratios
      in response to the variation in elemental composition of their food. This can
      also help them to bypass potential nutrient stoichiometric constraints. Our
      finding is an important step towards understanding the mechanisms contributing to
      the success of exotic species from stoichiometric principles.

PMID- 19401772
TI  - Antitumor activity and mechanism of action of the cyclopenta[b]benzofuran,
      silvestrol.
AB  - BACKGROUND: Flavaglines are a family of natural products from the genus Aglaia
      that exhibit anti-cancer activity in vitro and in vivo and inhibit translation
      initiation. They have been shown to modulate the activity of eIF4A, the DEAD-box
      RNA helicase subunit of the eukaryotic initiation factor (eIF) 4F complex, a
      complex that stimulates ribosome recruitment during translation initiation. One
      flavagline, silvestrol, is capable of modulating chemosensitivity in a mechanism
      based mouse model. METHODOLOGY/PRINCIPAL FINDINGS: Among a number of flavagline
      family members tested herein, we find that silvestrol is the more potent
      translation inhibitor among these. We find that silvestrol impairs the ribosome
      recruitment step of translation initiation by affecting the composition of the
      eukaryotic initiation factor (eIF) 4F complex. We show that silvestrol exhibits
      significant anticancer activity in human breast and prostate cancer xenograft
      models, and that this is associated with increased apoptosis, decreased
      proliferation, and inhibition of angiogenesis. We demonstrate that targeting
      translation by silvestrol results in preferential inhibition of weakly initiating
      mRNAs. CONCLUSIONS/SIGNIFICANCE: Our results indicate that silvestrol is a potent
      anti-cancer compound in vivo that exerts its activity by affecting survival
      pathways as well as angiogenesis. We propose that silvestrol mediates its effects
      by preferentially inhibiting translation of malignancy-related mRNAs. Silvestrol
      appears to be well tolerated in animals.

PMID- 19401774
TI  - In silico generation of alternative hypotheses using causal mapping (CMAP).
AB  - Previously, we introduced causal mapping (CMAP) as an easy to use systems biology
      tool for studying the behavior of biological processes that occur at the cellular
      and molecular level. CMAP is a coarse-grained graphical modeling approach in
      which the system of interest is modeled as an interaction map between functional
      elements of the system, in a manner similar to portrayals of signaling pathways
      commonly used by molecular cell biologists. CMAP describes details of the
      interactions while maintaining the simplicity of other qualitative methods (e.g.,
      Boolean networks).In this paper, we use the CMAP methodology as a tool for
      generating hypotheses about the mechanisms that regulate molecular and cellular
      systems. Furthermore, our approach allows competing hypotheses to be ranked
      according to a fitness index and suggests experimental tests to distinguish
      competing high fitness hypotheses. To motivate the CMAP as a hypotheses
      generating tool and demonstrate the methodology, we first apply this protocol to
      a simple test-case of a three-element signaling module. Our methods are next
      applied to the more complex phenomenon of cortical oscillations observed in
      spreading cells. This analysis produces two high fitness hypotheses for the
      mechanism that underlies this dynamic behavior and suggests experiments to
      distinguish the hypotheses. The method can be widely applied to other cellular
      systems to generate and compare alternative hypotheses based on experimentally
      observed data and using computer simulations.

PMID- 19401775
TI  - Intranasal flu vaccine protective against seasonal and H5N1 avian influenza
      infections.
AB  - BACKGROUND: Influenza A (flu) virus causes significant morbidity and mortality
      worldwide, and current vaccines require annual updating to protect against the
      rapidly arising antigenic variations due to antigenic shift and drift. In fact,
      current subunit or split flu vaccines rely exclusively on antibody responses for
      protection and do not induce cytotoxic T (Tc) cell responses, which are broadly
      cross-reactive between virus strains. We have previously reported that gamma-ray
      inactivated flu virus can induce cross-reactive Tc cell responses.
      METHODOLOGY/PRINCIPAL FINDING: Here, we report that intranasal administration of
      purified gamma-ray inactivated human influenza A virus preparations (gamma-Flu)
      effectively induces heterotypic and cross-protective immunity. A single
      intranasal administration of gamma-A/PR8[H1N1] protects mice against lethal H5N1
      and other heterotypic infections. CONCLUSIONS/SIGNIFICANCE: Intranasal gamma-Flu
      represents a unique approach for a cross-protective vaccine against both seasonal
      as well as possible future pandemic influenza A virus infections.

PMID- 19401776
TI  - Site directed mutagenesis of amino acid residues at the active site of mouse
      aldehyde oxidase AOX1.
AB  - Mouse aldehyde oxidase (mAOX1) forms a homodimer and belongs to the xanthine
      oxidase family of molybdoenzymes which are characterized by an essential
      equatorial sulfur ligand coordinated to the molybdenum atom. In general,
      mammalian AOs are characterized by broad substrate specificity and an yet obscure
      physiological function. To define the physiological substrates and the enzymatic
      characteristics of mAOX1, we established a system for the heterologous expression
      of the enzyme in Escherichia coli. The recombinant protein showed spectral
      features and a range of substrate specificity similar to the native protein
      purified from mouse liver. The EPR data of recombinant mAOX1 were similar to
      those of AO from rabbit liver, but differed from the homologous xanthine
      oxidoreductase enzymes. Site-directed mutagenesis of amino acids Val806, Met884
      and Glu1265 at the active site resulted in a drastic decrease in the oxidation of
      aldehydes with no increase in the oxidation of purine substrates. The double
      mutant V806E/M884R and the single mutant E1265Q were catalytically inactive
      enzymes regardless of the aldehyde or purine substrates tested. Our results show
      that only Glu1265 is essential for the catalytic activity by initiating the base
      catalyzed mechanism of substrate oxidation. In addition, it is concluded that the
      substrate specificity of molybdo-flavoenzymes is more complex and not only
      defined by the three characterized amino acids in the active site.

PMID- 19401778
TI  - The EG95 antigen of Echinococcus spp. contains positively selected amino acids,
      which may influence host specificity and vaccine efficacy.
AB  - Echinococcosis is a worldwide zoonotic parasitic disease of humans and various
      herbivorous domestic animals (intermediate hosts) transmitted by the contact with
      wild and domestic carnivores (definitive hosts), mainly foxes and dogs. Recently,
      a vaccine was developed showing high levels of protection against one parasite
      haplotype (G1) of Echinococcus granulosus, and its potential efficacy against
      distinct parasite variants or species is still unclear. Interestingly, the EG95
      vaccine antigen is a secreted glycosylphosphatydilinositol (GPI)-anchored protein
      containing a fibronectin type III domain, which is ubiquitous in modular proteins
      involved in cell adhesion. EG95 is highly expressed in oncospheres, the parasite
      life cycle stage which actively invades the intermediate hosts. After amplifying
      and sequencing the complete CDS of 57 Echinococcus isolates belonging to 7
      distinct species, we uncovered a large amount of genetic variability, which may
      influence protein folding. Two positively selected sites are outside the vaccine
      epitopes, but are predicted to alter protein conformation. Moreover, phylogenetic
      analyses indicate that EG95 isoform evolution is convergent with regard to the
      number of beta-sheets and alpha-helices. We conclude that having a variety of
      EG95 isoforms is adaptive for Echinococcus parasites, in terms of their ability
      to invade different hosts, and we propose that a mixture of isoforms could
      possibly maximize vaccine efficacy.

PMID- 19401777
TI  - Both strands of siRNA have potential to guide posttranscriptional gene silencing
      in mammalian cells.
AB  - Despite the widespread application of RNA interference (RNAi) as a research tool
      for diverse purposes, the key step of strand selection of siRNAs during the
      formation of RNA-induced silencing complex (RISC) remains poorly understood.
      Here, using siRNAs targeted to the complementary region of Survivin and the
      effector protease receptor 1 (EPR-1), we show that both strands of the siRNA
      duplex can find their target mRNA and are equally eligible for assembly into
      Argonaute 2 (Ago2) of RISC in HEK293 cells. Transfection of the synthetic siRNA
      duplexes with different thermodynamic profiles or short hairpin RNA (shRNA)
      vectors that generate double-stranded RNAs (dsRNAs), permitting processing
      specifically from either the 5' or 3' end of the incipient siRNA, results in the
      degradation of the respective target mRNAs of either strand of the siRNA duplex
      with comparable efficiencies. Thus, while most RNAi reactions may follow the
      thermodynamic asymmetry rule in strand selection, our study suggests an
      exceptional mode for certain siRNAs in which both strands of the duplex are
      competent in sponsoring RNAi, and implies additional factors that might dictate
      the RNAi targets.

PMID- 19401781
TI  - A postnatal critical period for orientation plasticity in the cat visual cortex.
AB  - Orientation selectivity of primary visual cortical neurons is an important
      requisite for shape perception. Although numerous studies have been previously
      devoted to a question of how orientation selectivity is established and
      elaborated in early life, how the susceptibility of orientation plasticity to
      visual experience changes in time remains unclear. In the present study, we
      showed a postnatal sensitive period profile for the modifiability of orientation
      selectivity in the visual cortex of kittens reared with head-mounted goggles for
      stable single-orientation exposure. When goggle rearing (GR) started at P16-P30,
      2 weeks of GR induced a marked over-representation of the exposed orientation,
      and 2 more weeks of GR consolidated the altered orientation maps. GR that started
      later than P50, in turn, induced the under-representation of the exposed
      orientation. Orientation plasticity in the most sensitive period was markedly
      suppressed by cortical infusion of NMDAR antagonist. The present study reveals
      that the plasticity and consolidation of orientation selectivity in an early life
      are dynamically regulated in an experience-dependent manner.

PMID- 19401779
TI  - A commensal Helicobacter sp. of the rodent intestinal flora activates TLR2 and
      NOD1 responses in epithelial cells.
AB  - Helicobacter spp. represent a proportionately small but significant component of
      the normal intestinal microflora of animal hosts. Several of these intestinal
      Helicobacter spp. are known to induce colitis in mouse models, yet the mechanisms
      by which these bacteria induce intestinal inflammation are poorly understood. To
      address this question, we performed in vitro co-culture experiments with mouse
      and human epithelial cell lines stimulated with a selection of Helicobacter spp.,
      including known pathogenic species as well as ones for which the pathogenic
      potential is less clear. Strikingly, a member of the normal microflora of
      rodents, Helicobacter muridarum, was found to be a particularly strong inducer of
      CXC chemokine (Cxcl1/KC, Cxcl2/MIP-2) responses in a murine intestinal epithelial
      cell line. Time-course studies revealed a biphasic pattern of chemokine responses
      in these cells, with H. muridarum lipopolysaccharide (LPS) mediating early (24-48
      h) responses and live bacteria seeming to provoke later (48-72 h) responses. H.
      muridarum LPS per se was shown to induce CXC chemokine production in HEK293 cells
      stably expressing Toll-like receptor 2 (TLR2), but not in those expressing TLR4.
      In contrast, live H. muridarum bacteria were able to induce NF-kappaB reporter
      activity and CXC chemokine responses in TLR2-deficient HEK293 and in AGS
      epithelial cells. These responses were attenuated by transient transfection with
      a dominant negative construct to NOD1, and by stable expression of NOD1 siRNA,
      respectively. Thus, the data suggest that both TLR2 and NOD1 may be involved in
      innate immune sensing of H. muridarum by epithelial cells. This work identifies
      H. muridarum as a commensal bacterium with pathogenic potential and underscores
      the potential roles of ill-defined members of the normal flora in the initiation
      of inflammation in animal hosts. We suggest that H. muridarum may act as a
      confounding factor in colitis model studies in rodents.

PMID- 19401783
TI  - Location of pathogenic bacteria during persistent infections: insights from an
      analysis using game theory.
AB  - Bacterial persistent infections are responsible for a significant amount of the
      human morbidity and mortality. Unlike acute bacterial infections, it is very
      difficult to treat persistent bacterial infections (e.g. tuberculosis). Knowledge
      about the location of pathogenic bacteria during persistent infection will help
      to treat such conditions by designing novel drugs which can reach such locations.
      In this study, events of bacterial persistent infections were analyzed using game
      theory. A game was defined where the pathogen and the host are the two players
      with a conflict of interest. Criteria for the establishment of Nash equilibrium
      were calculated for this game. This theoretical model, which is very simple and
      heuristic, predicts that during persistent infections pathogenic bacteria stay in
      both intracellular and extracellular compartments of the host. The result of this
      study implies that a bacterium should be able to survive in both intracellular
      and extracellular compartments of the host in order to cause persistent
      infections. This explains why persistent infections are more often caused by
      intracellular pathogens like Mycobacterium and Salmonella. Moreover, this
      prediction is in consistence with the results of previous experimental studies.

PMID- 19401780
TI  - Inactivation of DltA modulates virulence factor expression in Streptococcus
      pyogenes.
AB  - BACKGROUND: D-alanylated lipoteichoic acid is a virtually ubiquitous component of
      gram-positive cell walls. Mutations in the dltABCD operon of numerous species
      exhibit pleiotropic effects, including reduced virulence, which has been
      attributed to increased binding of cationic antimicrobial peptides to the more
      negatively charged cell surface. In this study, we have further investigated the
      effects that mutating dltA has on virulence factor expression in Streptococcus
      pyogenes. METHODOLOGY/PRINCIPAL FINDINGS: Isogenic Delta dltA mutants had
      previously been created in two distinct M1T1 isolates of S. pyogenes.
      Immunoblots, flow cytometry, and immunofluorescence were used to quantitate M
      protein levels in these strains, as well as to assess their ability to bind
      complement. Bacteria were tested for their ability to interact with human PMN and
      to grow in whole human blood. Message levels for emm, sic, and various regulatory
      elements were assessed by quantitative RT-PCR. Cell walls of Delta dltA mutants
      contained much less M protein than cell walls of parent strains and this
      correlated with reduced levels of emm transcripts, increased deposition of
      complement, increased association of bacteria with polymorphonuclear leukocytes,
      and reduced bacterial growth in whole human blood. Transcription of at least one
      other gene of the mga regulon, sic, which encodes a protein that inactivates
      antimicrobial peptides, was also dramatically reduced in Delta dltA mutants.
      Concomitantly, ccpA and rofA were unaffected, while rgg and arcA were up
      regulated. CONCLUSIONS/SIGNIFICANCE: This study has identified a novel mechanism
      for the reduced virulence of dltA mutants of Streptococcus pyogenes in which gene
      regulatory networks somehow sense and respond to the loss of DltA and lack of D
      alanine esterification of lipoteichoic acid. The mechanism remains to be
      determined, but the data indicate that the status of D-alanine-lipoteichoic acid
      can significantly influence the expression of at least some streptococcal
      virulence factors and provide further impetus to targeting the dlt operon of gram
      positive pathogens in the search for novel antimicrobial compounds.

PMID- 19401782
TI  - Pure ultrasonic communication in an endemic Bornean frog.
AB  - Huia cavitympanum, an endemic Bornean frog, is the first amphibian species known
      to emit exclusively ultrasonic (i.e., >20 kHz) vocal signals. To test the
      hypothesis that these frogs use purely ultrasonic vocalizations for intraspecific
      communication, we performed playback experiments with male frogs in their natural
      calling sites. We found that the frogs respond with increased calling to
      broadcasts of conspecific calls containing only ultrasound. The field study was
      complemented by electrophysiological recordings from the auditory midbrain and by
      laser Doppler vibrometer measurements of the tympanic membrane's response to
      acoustic stimulation. These measurements revealed that the frog's auditory system
      is broadly tuned over high frequencies, with peak sensitivity occurring within
      the ultrasonic frequency range. Our results demonstrate that H. cavitympanum is
      the first non-mammalian vertebrate described to communicate with purely
      ultrasonic acoustic signals. These data suggest that further examination of the
      similarities and differences in the high-frequency/ultrasonic communication
      systems of H. cavitympanum and Odorrana tormota, an unrelated frog species that
      produces and detects ultrasound but does not emit exclusively ultrasonic calls,
      will afford new insights into the mechanisms underlying vertebrate high-frequency
      communication.

PMID- 19401784
TI  - Does phenoloxidase contributed to the resistance? Selection with butane-fipronil
      enhanced its activities from diamondback moths.
AB  - Using microtitration method, the relationship between Phenoloxidase activity and
      the resistance of the diamondback moth Plutella xylostella (Linnaeus) to the
      novel insecticide butane-fipronil was determined in vitro. After selection of the
      tenth-generation by butane-fipronil, the resistance of the fourth instar larvae
      was increased 83.80-fold as compared to the susceptible strain. Phenoloxidase
      activity of the resistant strain (PO(r)) was 1.29-fold higher than the
      susceptible one (PO(s)). However, the Km and optimum pH values were similar in
      resistant and susceptible strains, which were 1.11 mM and 6.5, respectively. Both
      PO(r) and PO(s) have maximum stability at pH values less than 7.0, although PO(s)
      was less stable at lower pH values than PO(r). In addition, the thermal
      stabilities of the two phenoloxidase were very similar. It is suggested that PO
      may play an important role in the increasing resistance of pests to pesticides.

PMID- 19401785
TI  - Systems analysis of bioenergetics and growth of the extreme halophile
      Halobacterium salinarum.
AB  - Halobacterium salinarum is a bioenergetically flexible, halophilic microorganism
      that can generate energy by respiration, photosynthesis, and the fermentation of
      arginine. In a previous study, using a genome-scale metabolic model, we have
      shown that the archaeon unexpectedly degrades essential amino acids under aerobic
      conditions, a behavior that can lead to the termination of growth earlier than
      necessary. Here, we further integratively investigate energy generation, nutrient
      utilization, and biomass production using an extended methodology that accounts
      for dynamically changing transport patterns, including those that arise from
      interactions among the supplied metabolites. Moreover, we widen the scope of our
      analysis to include phototrophic conditions to explore the interplay between
      different bioenergetic modes. Surprisingly, we found that cells also degrade
      essential amino acids even during phototropy, when energy should already be
      abundant. We also found that under both conditions considerable amounts of
      nutrients that were taken up were neither incorporated into the biomass nor used
      as respiratory substrates, implying the considerable production and accumulation
      of several metabolites in the medium. Some of these are likely the products of
      forms of overflow metabolism. In addition, our results also show that arginine
      fermentation, contrary to what is typically assumed, occurs simultaneously with
      respiration and photosynthesis and can contribute energy in levels that are
      comparable to the primary bioenergetic modes, if not more. These findings portray
      a picture that the organism takes an approach toward growth that favors the here
      and now, even at the cost of longer-term concerns. We believe that the seemingly
      "greedy" behavior exhibited actually consists of adaptations by the organism to
      its natural environments, where nutrients are not only irregularly available but
      may altogether be absent for extended periods that may span several years. Such a
      setting probably predisposed the cells to grow as much as possible when the
      conditions become favorable.

PMID- 19401787
TI  - A comparative study of the effects of genistein, estradiol and raloxifene on the
      murine skeletal system.
AB  - Genistein, a major phytoestrogen of soy, is considered a potential drug for
      prevention and treatment of postmenopausal osteoporosis. The aim of the present
      study was to compare the effects of genistein, estradiol and raloxifene on the
      skeletal system in vivo and in vitro. Genistein (5 mg/kg), estradiol (0.1 mg/kg)
      or raloxifene hydrochloride (5 mg/kg) were administered daily by a stomach tube
      to mature ovariectomized Wistar rats for 4 weeks. Bone mass, mineral and calcium
      content, macrometric parameters and mechanical properties were examined. Also the
      effects of genistein, estradiol and raloxifene (10(-9)-10(-7) M) on the formation
      of osteoclasts from neonatal mouse bone marrow cells and the activity of
      osteoblasts isolated from neonatal mouse calvariae were compared. In vivo,
      estrogen deficiency resulted in the impairment of bone mineralization and bone
      mechanical properties. Raloxifene but not estradiol or genistein improved bone
      mineralization. Estradiol fully normalized the bone mechanical properties,
      whereas genistein augmented the deleterious effect of estrogen-deficiency on bone
      strength. In vitro, genistein, estradiol and raloxifene inhibited osteoclast
      formation from mouse bone marrow cells, decreasing the ratio of RANKL mRNA to
      osteoprotegerin mRNA expression in osteoblasts. Genistein, but not estradiol or
      raloxifene, decreased the ratio of alkaline phosphatase mRNA to ectonucleotide
      pyrophosphatase phosphodiesterase 1 mRNA expression in osteoblasts. This
      difference may explain the lack of genistein effect on bone mineralization
      observed in ovariectomized rats in the in vivo study. Concluding, our experiments
      demonstrated profound differences between the activities of genistein, estradiol
      and raloxifene towards the osseous tissue in experimental conditions.

PMID- 19401788
TI  - Inhibition of poly(ADP-ribose) polymerase activity affects its subcellular
      localization and DNA strand break rejoining.
AB  - Poly(ADP-ribose) polymerase (PARP) plays a crucial role in DNA repair. Modulation
      of its activity by stimulation or inhibition is considered as a potentially
      important strategy in clinical practice, especially to sensitize tumor cells to
      chemo- and radiotherapy through inhibition of DNA repair. Here we studied the
      effect of the three PARP inhibitors, 5-iodo-6-amino-benzopyrone (INH(2)BP), 1,5
      isoquinolinediol (1,5-dihydroxyisoquinolinediol (1,5-IQD) and 8-hydroxy-2
      methylquinazolin-4-[3H]one (NU1025), and for two of them the efficiency in
      slowing the rejoining of DNA strand breaks induced by H(2)O(2) was compared.
      Inhibition of PARP changed its intranuclear localization markedly; cells exposed
      to the inhibitor NU1025 showed a significant tendency to accumulate PARP in large
      foci, whereas in untreated cells its distribution was more uniform. The speed and
      efficiency of rejoining of H(2)O(2)-induced DNA strand breaks were lower in cells
      incubated with a PARP inhibitor, and the kinetics of rejoining were modulated in
      a different manner by each inhibitor. At a concentration of 100 microM the
      efficiency of the inhibitors could be ranked in the order NU1025 > IQD >
      INH(2)BP. The two first compounds were able to decrease the overall PARP activity
      below the level detected in control cells, while INH(2)BP showed up to 40% PARP
      activity after exposure to H(2)O(2).

PMID- 19401786
TI  - Transcription factor SP4 is a susceptibility gene for bipolar disorder.
AB  - The Sp4 transcription factor plays a critical role for both development and
      function of mouse hippocampus. Reduced expression of the mouse Sp4 gene results
      in a variety of behavioral abnormalities relevant to human psychiatric disorders.
      The human SP4 gene is therefore examined for its association with both bipolar
      disorder and schizophrenia in European Caucasian and Chinese populations
      respectively. Out of ten SNPs selected from human SP4 genomic locus, four
      displayed significant association with bipolar disorder in European Caucasian
      families (rs12668354, p = 0.022; rs12673091, p = 0.0005; rs3735440, p = 0.019;
      rs11974306, p = 0.018). To replicate the genetic association, the same set of
      SNPs was examined in a Chinese bipolar case control sample. Four SNPs displayed
      significant association (rs40245, p = 0.009; rs12673091, p = 0.002; rs1018954, p
      = 0.001; rs3735440, p = 0.029), and two of them (rs12673091, rs3735440) were
      shared with positive SNPs from European Caucasian families. Considering the
      genetic overlap between bipolar disorder and schizophrenia, we extended our
      studies in Chinese trios families for schizophrenia. The SNP7 (rs12673091, p =
      0.012) also displayed a significant association. The SNP7 (rs12673091) was
      therefore significantly associated in all three samples, and shared the same
      susceptibility allele (A) across all three samples. On the other hand, we found a
      gene dosage effect for mouse Sp4 gene in the modulation of sensorimotor gating, a
      putative endophenotype for both schizophrenia and bipolar disorder. The deficient
      sensorimotor gating in Sp4 hypomorphic mice was partially reversed by the
      administration of dopamine D2 antagonist or mood stabilizers. Both human genetic
      and mouse pharmacogenetic studies support Sp4 gene as a susceptibility gene for
      bipolar disorder or schizophrenia. The studies on the role of Sp4 gene in
      hippocampal development may provide novel insights for the contribution of
      hippocampal abnormalities in these psychiatric disorders.

PMID- 19401789
TI  - Multidrug-resistant tuberculosis: rapid molecular detection with MTBDRplus assay
      in clinical samples.
AB  - Nowadays, the greatest concern of tuberculosis control programmes is the
      appearance of multidrug-resistant tuberculosis and extensively drug-resistant
      tuberculosis. Rapid determination of drug resistance in clinical samples, with
      Mycobacterium tuberculosis complex (MTC), is the prerequisite for initiating
      effective chemotherapy, ensuring successful treatment of the patient and
      preventing further spread of drug-resistant isolates. The aim of our study was to
      determine the sensitivity of the new MTBDRplus assay in comparison to culture,
      identification and classic DST, directly from smear-positive clinical specimens.
      A total of 68 smear-positive sputum specimens were processed by both the
      classical mycobacteriological methods and the molecular assay, MTBDRplus.
      MTBDRplus assay allowed an accurate identification of MTC species by detection of
      the specific band in all samples, from which we also isolated and identified MTC
      strains by culture methods. In the samples from which we isolated susceptible
      strains (63.2%), wild type patterns were found using MTBDRplus assay. The samples
      from which we isolated resistant strains (36.8%) showed specific mutations
      associated with the correspondent resistant phenotype. Our study indicated that
      this assay allows rapid detection of resistance, always in agreement with classic
      methods.

PMID- 19401790
TI  - Asthma hospital admission and mortality in mainland Portugal 2000-2007.
AB  - We conducted a review of asthma hospital admissions in mainland Portugal 2000
      2007 to evaluate if one of the aims of the National Asthma Control Programme, a
      20% reduction in hospital admissions in children and adolescents in 2007, had
      been achieved. Using the Health Services Central Administration data base we
      reviewed 24271 admissions and saw that 48.7% of patients admitted were aged under
      19 years old and that 61.8% were aged 40 years old or under. Mean global annual
      asthma hospital admission rate was 30.79 per 100,000 inhabitants. Mean global
      hospital stay was 5.94 days, range 2.93 - 9.73 days, depending on the age group.
      We saw a drop in admission in both the northern and the Lisbon and Tagus Valley
      regions over the 8 year period. 189 patients died, 25 of who were aged 40 years
      old or under. The mortality rate ranged from 0.162 in 2002 to 0.324 per 100,000
      inhabitants in 2005, with a mean patient death of 0.77 patients per 100
      admissions. Mean annual costs were in excess of euro3.3 million, meaning an
      estimated annual financial asthma burden of around euro117.5 million in Portugal.
      We concluded that many asthma sufferers in Portugal do have sufficient disease
      controlled. Improved management would equal better quality of life and reduced
      disease costs.

PMID- 19401791
TI  - Home telemonitoring of severe chronic respiratory insufficient and asthmatic
      patients.
AB  - For 9 months we evaluated a portable device to transfer patient-clinician data by
      Internet: oximetry, ECG, clinical questionnaires and messages from the doctor.
      Fifty-one patients with severe chronic respiratory insufficiency (CRI) were
      followed at the hospital Pulido Valente and Espirito Santo and 21 asthmatics (A)
      were followed at the latter hospital. The use and acceptance of this device was
      evaluated through questionnaires soliciting patients' and health professionals'
      opinions. Patients with CRI followed in Lisbon were also asked about hospital
      admissions and quality of life compared with a nine month period before the
      monitoring programme. CRI patients found learning to use the system more
      difficult; the majority (80%) reported problems with the equipment, qualified as
      rare/occasional in 62% of the cases. For 31 CRI patients followed in Lisbon, the
      use of the system was classified as correct in 12 patients, incorrect in 7 and
      reasonable in 12 patients. The first group had a reducded number and duration of
      hospital admissions and also improved quality of life. With this remote
      monitoring system 80% of CRI patients reported they were more/much more supported
      and 33 patients (75%) would use this system in the future. 81% of asthmatic
      patients would also like to maintain this type of monitoring. The service was
      considered useful by the researchers. We concluded that home telemonitoring was a
      positive contribution to the management of chronic patients and raised awareness
      of it should be considered in the future.

PMID- 19401792
TI  - Obstructive sleep apnoea syndrome as a cause of road traffic accidents.
AB  - Several studies have demonstrated that obstructive sleep apnoea syndrome (OSAS)
      patients have a higher rate of road traffic accidents. Our study aimed to analyse
      any differences in OSAS patients between those who reported having had road
      traffic accidents and/or near misses and those who did not. METHODS: We studied
      163 patients with OSAS (apnoea- hypopnoea index (AHI)>10/h) diagnosed using
      nocturnal polysomnography (NPSG), all drivers, 18.4% of whom drove for a living.
      Patients were asked at their first clinical interview to self-report road traffic
      accidents and/or near misses over the past 3 years which had been caused by
      abnormal daytime drowsiness. This allowed patients to be divided into two groups,
      those who had had road traffic accidents and/or near misses and those who had
      not. Both were compared as to age, body mass index (BMI), Epworth Sleepiness
      Scale (ESS), daytime PaO2 and PaCO2, Functional Outcomes of Sleep Questionnaire
      (FOSQ) test and NPSG data. This latter was total sleep time (TTS), sleep
      efficiency, sleep stages, arousal index (ARI), AHI, minimal and average SaO2, %
      of time with SaO2 < 90% (T90), desaturation index (ODI), total duration of apnoea
      hypopnoea (TDAH) (T test). RESULTS: Group I (no road traffic accidents) No=89
      patients; group II (road traffic accidents) No=74 patients. Age (years) was
      57.6+/-11.8 vs. 54.7+/-10.9 (ns); male gender, 75% vs. 78.4%; ESS, 12.3+/-5.4 vs.
      17.6+/-4.3 (p<0.001); BMI, (Kg/m2) 36.2+/-8.1 vs. 35.6+/-6.3 (ns); PaO2 (mmHg),
      76.1+/-11.4 vs. 78.5+/-12.6 (ns); PaCO2 (mmHg), 42.6+/-5.1 vs. 42.2+/-4.7 (ns);
      FOSQ, 15.1+/-3.1 vs. 12.9+/-3.4 (p<0.001). NPSG data revealed differences only in
      AHI: 45.0+/-21.6 vs. 56.2+/-29.7 (p=0.01) and in TDAH (minutes), 98.5+/-63.7 vs.
      133.3+/-83.2 (p=0,005). CONCLUSIONS: In our experience patients who had road
      traffic accidents and/or near misses had a more severe OSAS, with higher AHI,
      excessive daytime sleepiness and lower quality of life.

PMID- 19401793
TI  - Interstitial lung disease: diagnostic accuracy and safety of surgical lung
      biopsy.
AB  - This study reports our experience, diagnostic accuracy and safety of surgical
      lung biopsy in patients with interstitial lung diseases. From January 1998 -
      December 2007 surgical lung biopsy was performed in 53 patients (22 female
      [41.5%]; age 47.2+/-13 years). A total of 37 patients (69.8%) underwent
      videothoracoscopic lung biopsy and minithoracotomy was performed in 16 patients
      (30.2%). Right lung was the choice in 47 patients (88.7%). Postoperative
      complications were rare (9.4%) and included three prolonged air leaks (5.7%), one
      pneumothorax requiring a chest drain (1.9%), and one haemothorax requiring
      reoperation (1.9%). One patient died of cardiac arrest of unknown cause. Average
      chest tube duration was 4.4+/-3 days and average hospital stay 5.4+/-4 days. Lung
      biopsy contributed to the diagnosis in 50 patients (94.3%). In conclusion, the
      potential benefits of diagnostic surgical lung biopsy must be considered against
      the risks of the procedure especially in patients with severe cardiopulmonary
      dysfunction.

PMID- 19401794
TI  - [Airways inflammation evaluation. Upper and lower airways].
AB  - It is done a review of evaluation methods of the inflammation in upper airways
      and bronchi used for diagnosis, therapeutic approach and prognosis of pathologies
      like rhinosinusitis and asthma. It is also analysed methods that supply relevant
      information of inflammation in COPD. The chronic inflammation of the airways is
      associated to respiratory distress, obstruction in basal lung function tests and
      to bronchial and nasal hyperreactivity. Computerized tomography informs about
      lumen dimensions, bronchial walls thickness and pulmonary density. These changes
      are associated to inflammation and to remodelling of the airways. Localized
      inflammation in respiratory tract can be detected by modifications of systemic
      inflammatory markers. The direct evaluation of inflammatory airways changes are
      based on immune, histological and chemical analysis of lung tissue obtained by
      biopsies and by fluids recoil in basal conditions or after stimulation. The
      eosinophils are increased in biopsies and in nasal and bronchoalveolar lavage in
      asthma and rhinitis and can change with therapy. Proteins and mRNA expression of
      cellular activation mediators are also observed. The induced sputum identifies
      eosinophilic inflammation that is inversely associated with lung function
      parameters. In each respiratory cycle the air is enriched in organic volatile
      compounds produced by cellular breathing. FENO is the bio marker more deeply
      studied in asthma and its increase is well documented in this disorder. In the
      exhaled air condensed, reactive oxygen species, membrane mediators, cytokines,
      and chemokines are identified. If the non invasive evaluation of inflammation
      became reliable and reproducible it will be indispensable in monitoring the
      airways diseases.

PMID- 19401795
TI  - [The role of the epithelial cell in asthma].
AB  - It is done a review of the intervention of the epithelial bronchial cell in the
      pathophysiology of asthma. The respiratory epithelium acts as a physical barrier
      that separates the external environment from the pulmonary internal environment.
      It controls the intercellular and trans -cellular permeability and this way the
      accessibility of the inhaled pathogens to the antigen presenting cells involved
      in the immuno -inflammatory response. Epithelial cells connected by tight
      junctions contribute to the barrier function of the airways. They express a
      poliovirus receiver - related protein (PRR), toll like receptors (TLRs) and
      protease- -activated receptors (PARs), which recognize bacterial agents and
      allergens. Its dysfunction turns them into important sources of inflammatory
      mediators. The bidirectional interaction between the epithelium and other
      bronchial wall elements with inhaled particles originates a structure with its
      own identity, the designated EMTU - Epithelial Mesenchymal Trophic Unit. These
      observations support a central role for the epithelial cell in chronic
      inflammation and in the remodelling of the asthmatic process. Infectious diseases
      and environmental stress can activate different cell receptors and signalling
      pathways that induce changes in the cell surface modifying their response to
      future stimulations, namely to other infectious aggressions. The bronchial
      epithelium has barrier functions with selective permeability; it has metabolic
      activity producing cytokines and chemokines stimulating the cell's recruitment
      and activation, increasing the bronchial reactivity and the remodelling of the
      airways.

PMID- 19401796
TI  - [Alpha-1 antitrypsin deficiency. The experience of Pulido Valente Hospital with
      augmentation therapy].
AB  - Alpha-1 antitrypsin (AAT) is synthesised in the liver and has half-life of 4-5
      days. AAT has antiprotease activity, with particular affinity for neutrophil
      elastase. Its deficiency leads to a lack of effective lung protection against
      activated neutrophil enzymes. Deficiency of AAT is a genetic disorder that occurs
      as a result of the inheritance of two protease inhibitor deficient alleles. Of
      the deficient alleles, Pi*Z is the most common, and the homozygous form Pi*ZZ
      results in the lowest serum levels, usually below 50 mg/ dl. The "protective
      threshold" is 80 mg/dl. Smoking increases the risk of emphysema. The current goal
      of augmentation therapy is to raise the plasma levels, above protective threshold
      and slow disease progression. The authors present the experience of the Day Care
      Hospital of the Pulido Valente Hospital with five male patients presenting
      emphysema due to AAT deficiency, receiving weekly intravenous treatment with
      Prolastin. We performed a clinical, respiratory functional and radiological
      evaluation between 2003 and 2007. The results point to a slower progression of
      the disease, with clinical and radiological stability and a reduced rate of FEV1
      decline. Augmentation therapy is an expensive treatment and its use is lacking
      supportive evidence of efficacy by randomized controlled clinical trials.
      Evidence that it confers benefits is based on observational studies. Our
      experience is positive, showing clinical, radiological and functional benefits.
      The literature available points to a decrease in mortality, but we could not
      affirm so in our small population.

PMID- 19401797
TI  - [Update in pulmonary thromboembolic disease].
AB  - Pulmonary embolism is part of venous thromboembolism, an important health problem
      which leads to significant mortality and morbidity with high economic and social
      burden. A prompt diagnosis and treatment as well as an appropriate prophylaxis
      are determinant factors in prognosis. This disease continues to demand particular
      attention namely in the investigation of risk factors, clinical probability
      algorithms development, diagnostic work-up evaluation, characterization of new
      therapeutic strategies and thromboprophylaxis recommendations. The present review
      looks into the current scientific knowledge regarding pulmonary embolism.

PMID- 19401798
TI  - Thoracic empyema - a review based on three cases reports.
AB  - Complicated parapneumonic effusion is one in which an invasive procedure is
      necessary for its resolution and empyema means pus in the pleural space. An early
      diagnosis and therapy of these conditions results in less morbidity and
      mortality. CT of the chest is important to study complex pleural effusions.
      Loculated effusions, those occupying more than 50% of the thorax, or which show
      positive Gram stain or bacterial culture, or a purulent effusion with a pH below
      7.20, with a glucose level below 60 mg/dl or a LDH level more than three times
      the upper limit of normal for serum, are indications for an invasive procedure.
      These characteristics result from the evolution of a not well treated
      parapneumonic effusion, through the three stages: (1) exsudative; (2)
      fibrinopurulent; (3) fibrotic. Depending on the stage therapeutic methods vary
      from therapeutic thoracentesis, insertion of a chest tube with or without
      instillation of fibrinolytics, video-assisted thoracoscopic surgery, and lung
      decortication. A review of all these aspects are done based on a series of three
      cases reports with very different clinical presentation: one patient with empyema
      by Streptococcus pyogenes and that died rapidly due to massive hemoptysis; a
      patient with empyema due to acute pneumonia developing during an airflight; a
      patient with empyema and bacteraemia by Streptococcus pneumonia leading to the
      diagnosis of an unknown HIV infection.

PMID- 19401799
TI  - [Chylothorax - case report].
AB  - Chylothorax is the occurrence of lymph in the pleura due to damage or obstruction
      of the thoracic duct. High content of triglycerides and the presence of
      chylomicrons make the diagnosis of chylothorax. Its aetiology can be divided in
      traumatic and non-traumatic. Traumatic rupture occurs after accidents or surgery.
      Within non-traumatic aetiology, lymphoma is the most common and in the presence
      of a chylothorax of unknown origin this should be the first suspicion, being non
      Hodgkin type the most frequent. The authors present a case report of a patient
      with chylothorax due to non-Hodgkin lymphoma, discuss the particularities of
      chylothorax as well as the investigation and its treatment options.

PMID- 19401800
TI  - [Principle of autonomy: right of self-disposal till the end? A case report].
AB  - The doctor-patient relationship should be established in ethical principles. The
      codes of conduct that guide the relation between the doctor and the patient are
      addressed to the physician (principle of beneficence and non-maleficence) or
      oriented to the patient (principle of autonomy). As such, in certain
      circumstances there can be some tension between the principles. Based on a case
      report in a setting of principles conflict, ethical and legal considerations are
      made so far as the doctor's attitude is concerned.

PMID- 19401801
TI  - [Post-tracheal extubation pulmonary oedema - case report].
AB  - Negative pressure pulmonary oedema is an uncommon complication of traqueal
      extubation (approximately 0,1%) mostly caused by acute upper airway obstruction.
      Upper airway obstruction from glottis closure leads to marked inspiratory effort,
      which generates negative intrathoracic pressure transmitting to pulmonary
      interstitium, and inducing fluid transudation from pulmonary capillary bed(1-5).
      We report a case of post-extubation pulmonary oedema in a fifteen years old
      patient, submitted to surgery following traumatic amputation of his left leg. We
      review the pathophysiology, radiological findings, potential risk factors and
      preventive measures of this post-anaesthetic respiratory complication.

PMID- 19401802
TI  - Sarcoidosis: a less common presentation.
AB  - The clinical presentation of sarcoidosis is diverse and in over 90% of patients
      there is pulmonary involvement. The most common features of the radiographic
      findings at the time of diagnosis are bilateral hilar lymphadenopathy and
      pulmonary infiltration. The authors report the case of a young female patient who
      presented with multiple bilateral nodular shadows on chest radiograph. Surgical
      biopsy revealed non-necrotizing granulomas with occasional multinucleated giant
      cells compatible with sarcoidosis. Although this was a case of stage III
      pulmonary disease, the patient was asymptomatic, lung function tests were normal
      and there were no signs of extrathoracic involvement. Spontaneous remission
      occurred without treatment as shown on high resolution CT scan follow-up, one
      year later.

PMID- 19401803
TI  - Cold winter temperatures condition the egg-hatching dynamics of a grape disease
      vector.
AB  - The leafhopper Scaphoideus titanus is the vector of a major phytoplasma grapevine
      disease, Flavescence doree. The vector's distribution is in Eastern and Northern
      Europe, and its population dynamics varies as a function of vineyard latitude. We
      tested the hypothesis that hatching dynamics are cued by cold temperatures
      observed in winter. We exposed eggs from a natural population to simulated "cold"
      and "mild" winters and varied the exposure time at 5 degrees C from 0 to 63 days.
      We show that temperature cooling mainly affected the onset of hatching and is
      negatively correlated to the cold time exposure. The majority of hatchings
      occurred more quickly in cold rather than in mild winter simulated conditions,
      but there was no significant difference between the duration of hatching of eggs
      whatever the cold time exposure. In agreement with the Northern American origin
      of the vector, the diapause termination and thus the timing regulation of egg
      hatching require cold winters.

PMID- 19401804
TI  - Long-lasting benefits of botulinum toxin type B in Parkinson's disease-related
      drooling.
AB  - PURPOSE: To investigate the safety, efficacy and effectiveness of botulinum toxin
      type-B (BTX-B) injections into the parotid glands to reduce drooling in
      Parkinson's disease (PD) subjects. METHODS: A double-blind, randomised, placebo
      controlled study enrolled 36 advanced phase PD subjects who complained of
      disabling drooling. Patients received either 4000U BTX-B or placebo. Anatomically
      guided injections were performed. Outcome measures were chosen to assess both the
      subjective feeling of improvement (i. e. the Drooling Severity and Frequency
      Scale, DSFS, visuo-analogic ratings of familial distress, VAS-FD, and social
      distress, VAS-SD) and objective saliva reduction (saliva production over five
      minutes was checked by weighing dental rolls). The Global Impression Score (GIS)
      was also applied, rating improvement from 0 to 3. RESULTS: One month after
      injections, BTX-B patients showed a meaningful improvement in almost all
      subjective outcomes. Two-way analysis of variance gave a significant time x
      treatment effect, F-value being 52.5 (p < 0.0001) for DS-FS, 23.2 (p < 0.0001)
      for VAS-FD, 29 (p < 0.0001) for VAS-SD, and 28.9 (p < 0.0001) for UPDRSADL
      drooling item score. All BTX-B subjects declared sialorrhea reduction of any kind
      (moderate for 44.4% cases, and dramatic for 33.3% subjects), at variance with
      61.1% controls who denied any benefit from treatment. (Chi-square = 22.9; p <
      0.0001). When present, benefits lasted on average 19.2 +/- 6.3 weeks in the BTX-B
      group compared to 6.7 +/- 1.4 weeks in controls (T-value: 26.4; p < 0.0001).
      CONCLUSIONS: BTXB represents a safe and efficacious tool for the management of PD
      related drooling, ensuring a longlasting waning of this disabling symptom.

PMID- 19401805
TI  - Convexity subarachnoid haemorrhage associated with bilateral internal carotid
      artery stenoses.

PMID- 19401806
TI  - What determines healthcare utilization and related out-of-pocket expenditures in
      Tajikistan? Lessons from a national survey.
AB  - OBJECTIVES: The government of Tajikistan is currently exploring the ways to test
      the possible introduction of a Basic Benefit Package which is to provide
      healthcare for the most vulnerable groups within the population. In this context,
      the objective of this study is to analyze individual, household, geographical and
      systemic factors which explain healthcare utilization and out-of-pocket
      expenditures in Tajikistan. METHODS: Using a nationally-representative survey,
      the author examines the determinants of healthcare utilization and its related
      out-of-pocket expenditures. Two empirical multivariate models are employed:
      binomial logit regression to estimate the determinants of healthcare utilization
      and Tobit regression to estimate the determinants of out-of-pocket expenditures.
      RESULTS: An increase in the ability to pay is associated with a higher propensity
      to utilize healthcare. Likewise, being a woman, being elderly, having higher
      educational attainment and having chronic illness also increase the propensity to
      utilize healthcare. Conversely, needing to travel a long distance to health post
      reduces the likelihood of utilization. An increase in ability to pay, being
      female and using specialized healthcare facilities increases the amount of out-of
      pocket expenditures. In contrast, using ancillary healthcare personnel and
      outpatient facilities reduced the amount of out-of-pocket expenditures.
      CONCLUSIONS: Linking receipt of the package with targeted social assistance and
      development of Community Based social insurance scheme can improve accessibility
      and affordability of healthcare.

PMID- 19401808
TI  - Conformational rearrangements of plasminogen activator inhibitor type 2.

PMID- 19401809
TI  - Library-based numerical reduction of the Hodgkin-Huxley neuron for network
      simulation.
AB  - We present an efficient library-based numerical method for simulating the Hodgkin
      Huxley (HH) neuronal networks. The key components in our numerical method involve
      (i) a pre-computed high resolution data library which contains typical neuronal
      trajectories (i.e., the time-courses of membrane potential and gating variables)
      during the interval of an action potential (spike), thus allowing us to avoid
      resolving the spikes in detail and to use large numerical time steps for evolving
      the HH neuron equations; (ii) an algorithm of spike-spike corrections within the
      groups of strongly coupled neurons to account for spike-spike interactions in a
      single large time step. By using the library method, we can evolve the HH
      networks using time steps one order of magnitude larger than the typical time
      steps used for resolving the trajectories without the library, while achieving
      comparable resolution in statistical quantifications of the network activity,
      such as average firing rate, interspike interval distribution, power spectra of
      voltage traces. Moreover, our large time steps using the library method can break
      the stability requirement of standard methods (such as Runge-Kutta (RK) methods)
      for the original dynamics. We compare our library-based method with RK methods,
      and find that our method can capture very well phase-locked, synchronous, and
      chaotic dynamics of HH neuronal networks. It is important to point out that, in
      essence, our library-based HH neuron solver can be viewed as a numerical
      reduction of the HH neuron to an integrate-and-fire (I&F) neuronal representation
      that does not sacrifice the gating dynamics (as normally done in the analytical
      reduction to an I&F neuron).

PMID- 19401810
TI  - Spatial analysis and facility characteristics of outdoor recreational areas in
      Istanbul.
AB  - This article reports the results of a study that explored whether outdoor
      recreational areas are sufficient in Istanbul in terms of their surface area and
      facility characteristics. All the municipalities in 32 subprovinces of Istanbul
      were sent a survey in 2007 and asked to prepare a list of their outdoor
      recreational areas including their names, addresses, size, and facilities. All
      the data collected from the municipalities were used to create a GIS-based
      inventory by using GIS and remote sensing. As the study revealed, the outdoor
      recreational areas in Istanbul are far behind meeting the recreational needs of
      the residents in terms of area per person and facility characteristics. There are
      2,470 areas which were dedicated to outdoor recreational activities in Istanbul.
      Total surface area of all these outdoor recreational areas is 19,2 sq kilometers;
      this means 1.52 m(2) recreational area per person in the city. This value is very
      low when compared to that of many cities in Europe and USA. As the study also
      revealed, the majority of outdoor recreational areas in Istanbul are poor in
      facility. Majority of the existing outdoor recreational areas are small and do
      not provide the public with many opportunities to engage in different outdoor
      activities. A more sustainable and efficient recreational plan is needed in
      Istanbul to meet the various recreational needs of its residents.

PMID- 19401811
TI  - Using dual classifications in the development of avian wetland indices of
      biological integrity for wetlands in West Virginia, USA.
AB  - Considerable resources are being used to develop and implement bioassessment
      methods for wetlands to ensure that "biological integrity" is maintained under
      the United States Clean Water Act. Previous research has demonstrated that avian
      composition is susceptible to human impairments at multiple spatial scales. Using
      a site-specific disturbance gradient, we built avian wetland indices of
      biological integrity (AW-IBI) specific to two wetland classification schemes, one
      based on vegetative structure and the other based on the wetland's position in
      the landscape and sources of water. The resulting class-specific AW-IBI was
      comprised of one to four metrics that varied in their sensitivity to the
      disturbance gradient. Some of these metrics were specific to only one of the
      classification schemes, whereas others could discriminate varying levels of
      disturbance regardless of classification scheme. Overall, all of the derived
      biological indices specific to the vegetative structure-based classes of wetlands
      had a significant relation with the disturbance gradient; however, the biological
      index derived for floodplain wetlands exhibited a more consistent response to a
      local disturbance gradient. We suspect that the consistency of this response is
      due to the inherent nature of the connectivity of available habitat in floodplain
      wetlands.

PMID- 19401812
TI  - Performance traits and metabolic responses in goats (Capra hircus) supplemented
      with inorganic trivalent chromium.
AB  - The effects of supplemental chromium (Cr) as chromic chloride hexahydrate in
      incremental dose levels (0, 0.5, 1.0, and 1.5 mg/day for 240 days) on metabolism
      of nutrients and trace elements were determined in dwarf Bengal goats (Capra
      hircus, castrated males, average age 3 months, n = 24, initial mean body weight
      6.4 +/- 0.22 kg). Live weight increased linearly (p < 0.05) with the level of
      supplemental Cr. Organic matter and crude protein digestibility, intake of total
      digestible nutrients, and retention of N (g/g N intake) increased (p < 0.05) in a
      dose-dependent linear manner. Serum cholesterol and tryacylglycerol
      concentrations changed inversely with the dose of supplemental Cr (p < 0.01).
      Supplemental Cr positively influenced retention of copper and iron (p < 0.05)
      causing linear increase (p < 0.01) in their serum concentrations. It was
      concluded that Cr supplementation may improve utilization of nutrients including
      the trace elements and may also elicit a hypolidemic effect in goats. However,
      further study with regards to optimization of dose is warranted.

PMID- 19401814
TI  - Peculiar intracytoplasmic basophilic bodies in papillary thyroid carcinoma.

PMID- 19401818
TI  - Plant vaccines: an immunological perspective.
AB  - The advent of technologies to express heterologous proteins in planta has led to
      the proposition that plants may be engineered to be safe, inexpensive vehicles
      for the production of vaccines and possibly even vectors for their delivery. The
      immunogenicity of a variety of antigens of relevance to vaccination expressed in
      different plants has been assessed. The purpose of this article is to examine the
      utility of plant-expression systems in vaccine development from an immunological
      perspective.

PMID- 19401819
TI  - Display of peptides on the surface of tobacco mosaic virus particles.
AB  - In this review, we focus on the potential that tobacco mosaic virus (TMV) has as
      a carrier for immunogenic epitopes, and the factors that must be considered in
      order to bring products based on this platform to the market. Large Scale Biology
      Corporation developed facile and scaleable methods for manufacture of candidate
      peptide display vaccines based on TMV. We describe how rational design of peptide
      vaccines can improve the manufacturability of particular TMV products. We also
      discuss downstream processing and purification of the vaccine products, with
      particular attention to the metrics that a product must attain in order to meet
      criteria for regulatory approval as injectable biologics.

PMID- 19401813
TI  - Expression of p18(INK4C) is down-regulated in human pituitary adenomas.
AB  - Cyclin-dependent kinase inhibitors represented by the INK4 family comprising
      p16(INK4A), p15(INK4B), p18(INK4C), and p19(INK4D) are regulators of the cell
      cycle shown to be aberrant in many types of cancer. Mice lacking p18(Ink4c)
      exhibit a series of phenotypes including the development of widespread
      organomegaly and pituitary adenomas. The objective of our study is to examine the
      role of p18(INK4C) in the pathogenesis of human pituitary tumors. The protein and
      mRNA levels of p18(INK4C) were examined by immunohistochemistry and real-time
      reverse transcription-polymerase chain reaction, respectively. The methylation
      status of the p18(INK4C) gene promoter and somatic mutations of the p18(INK4C)
      gene were also investigated. p18(INK4C) protein expression was lost or
      significantly reduced in 64% of pituitary adenomas compared with levels in normal
      pituitary glands. p18(INK4C) mRNA levels were low in all ACTH adenomas and non
      functioning (NF)-FSH and in 42%, 70% and 66% of GH, PRL, and subtype 3 adenomas,
      respectively. p18(INK4C) mRNA levels were significantly associated with
      p18(INK4C) protein levels. Neither methylated promoters in pituitary adenomas,
      except in one NF-FSH adenoma, nor somatic mutations of the p18(INK4C) gene in any
      pituitary adenomas were detected. The down-regulation of p18(INK4C) expression
      may contribute to the tumorigenesis of pituitary adenomas.

PMID- 19401820
TI  - Chloroplast-derived vaccine antigens and biopharmaceuticals: expression, folding,
      assembly and functionality.
AB  - Chloroplast genetic engineering offers several advantages, including high levels
      of transgene expression, transgene containment via maternal inheritance, and
      multi-gene expression in a single transformation event. Oral delivery is
      facilitated by hyperexpression of vaccine antigens against cholera, tetanus,
      anthrax, plague, or canine parvovirus (4%-31% of total soluble protein, TSP) in
      transgenic chloroplasts (leaves) or non-green plastids (carrots, tomato) as well
      as the availability of antibiotic free selectable markers or the ability to
      excise selectable marker genes. Hyperexpression of several therapeutic proteins,
      including human serum albumin (11.1% TSP), somatotropin (7% TSP), interferon
      alpha (19% TSP), interferon-gamma (6% TSP), and antimicrobial peptide (21.5%
      TSP), facilitates efficient and economic purification. Also, the presence of
      chaperones and enzymes in chloroplasts facilitates assembly of complex
      multisubunit proteins and correct folding of human blood proteins with proper
      disulfide bonds. Functionality of chloroplast-derived vaccine antigens and
      therapeutic proteins has been demonstrated by several assays, including the
      macrophage lysis assay, GM1-ganglioside binding assay, protection of HeLA cells
      or human lung carcinoma cells against encephalomyocarditis virus, systemic immune
      response, protection against pathogen challenge, and growth or inhibition of cell
      cultures. Purification of human proinsulin has been achieved using novel
      purification strategies (inverse temperature transition property) that do not
      require expensive column chromatography techniques. Thus, transgenic chloroplasts
      are ideal bio-reactors for production of functional human and animal therapeutic
      proteins in an environmentally friendly manner.

PMID- 19401822
TI  - Plant production of veterinary vaccines and therapeutics.
AB  - Plant-derived biologicals for use in animal health are becoming an increasingly
      important target for research into alternative, improved methods for disease
      control. Although there are no commercial products on the market yet, the
      development and testing of oral, plant-based vaccines is now beyond the proof-of
      principle stage. Vaccines, such as those developed for porcine transmissible
      gastroenteritis virus, have the potential to stimulate both mucosal and systemic,
      as well as, lactogenic immunity as has already been seen in target animal trials.
      Plants are a promising production system, but they must compete with existing
      vaccines and protein production platforms. In addition, regulatory hurdles will
      need to be overcome, and industry and public acceptance of the technology are
      important in establishing successful products.

PMID- 19401821
TI  - Production of antibodies in plants: approaches and perspectives.
AB  - Advances in molecular biology, immunology, and plant biotechnology have changed
      the paradigm of plant as a food source to so-called plant bioreactor to produce
      valuable recombinant proteins. These include therapeutic or diagnostic monoclonal
      antibodies, vaccines, and other biopharmaceutical proteins. The plant as a
      bioreactor for the production of therapeutic proteins has several advantages,
      which include the lack of animal pathogenic contaminants, low cost of production,
      and ease of agricultural scale-up compared to other currently available systems.
      Thus, plants are considered to be a potential alternative to compete with other
      systems such as bacteria, yeast, or insect and mammalian cell culture. Plant
      production systems, particularly therapeutic antibodies, are very attractive to
      pharmaceutical companies to produce the antibodies in demand. Currently, we have
      successfully developed a plant system for production of anti-rabies monoclonal
      antibody and anti-colorectal cancer monoclonal antibody. The effective plant
      production system for recombinant antibodies requires the appropriate plant
      expression machinery with optimal combination of transgene expression regulatory
      elements, control of posttranslational protein processing, and efficient
      purification methods for product recovery. However, there are several limitations
      that have to be resolved to establish the efficient plant system for antibody
      production. Here, we discuss the approaches and perspectives in plant systems to
      produce monoclonal antibody.

PMID- 19401823
TI  - Plant-based oral vaccines: results of human trials.
AB  - Vaccines consisting of transgenic plant-derived antigens offer a new strategy for
      development of safe, inexpensive vaccines. The vaccine antigens can be eaten with
      the edible part of the plant or purified from plant material. In phase 1 clinical
      studies of prototype potato- and corn-based vaccines, these vaccines have been
      safe and immunogenic without the need for a buffer or vehicle other than the
      plant cell. Transgenic plant technology is attractive for vaccine development
      because these vaccines are needle-less, stable, and easy to administer. This
      chapter examines some early human studies of oral transgenic plant-derived
      vaccines against enterotoxigenic Escherichia coli infection, norovirus, and
      hepatitis B.

PMID- 19401824
TI  - Relationship between glyco-oxidation, antioxidant status and microalbuminuria in
      type 2 diabetic patients.
AB  - AIMS/HYPOTHESIS: This study examined the relationship, if any, between glucose
      induced oxidative stress, antioxidant status and microalbuminuria in patients
      with type 2 diabetes. METHODS: The study involved 99 consecutive type 2 diabetic
      patients (57 men, 42 women). Patients with persistent microalbuminuria were
      identified and the following variables evaluated: fasting plasma glucose,
      HbA(1c), malonyldialdehyde (MDA), pentosidine, AGE, the total radical-trapping
      antioxidant parameter (TRAP), vitamin E, creatinine, estimated GFR and lipid
      profile. RESULTS: Patients were divided into two groups, i.e. 37 individuals
      without microalbuminuria (AER <20 microg/min) and 62 with microalbuminuria (AER >
      or =20 microg/min). The following variables were significantly higher in patients
      with microalbuminuria than in those without microalbuminuria (mean +/- SD):
      fasting plasma glucose 9.41 +/- 2.88 vs 8.19 +/- 1.93 mmol/l, p < 0.05; HbA(1c)
      7.97 +/- 1.51 vs 7.39 +/- 1.03%, p < 0.05; MDA 1.18 +/- 0.35 vs 1.02 +/- 0.29
      micromol/l, p < 0.05; pentosidine 98.5 +/- 24.6 vs 82.9 +/- 20.9 pmol/ml, p <
      0.005; and AGE 13.2 +/- 4.8 vs 10.6 +/- 3.8 microg/mg protein, p < 0.01. However,
      vitamin E and TRAP did not differ between the two groups. Serum creatinine values
      and estimated GFR were similar in the two groups. Only in patients with
      microalbuminuria were significant linear correlations seen between AER and both
      oxidation (HbA(1c) r = 0.33, p < 0.01; MDA r = 0.59, p < 0.001; pentosidine r =
      0.48, p < 0.001; and AGE r = 0.44, p < 0.001) and antioxidation variables
      (vitamin E r = -0.55, p < 0.001; TRAP r = -0.49, p < 0.001). Considering all
      variables together, multiple regression revealed a correlation between
      microalbuminuria and vitamin E, TRAP, HbA(1c) and MDA, but not pentosidine or
      AGE. CONCLUSIONS/INTERPRETATION: Our data suggest that microalbuminuria in type 2
      diabetic patients might be promoted by an insufficient counter-regulation of the
      antioxidant system in the event of increased glyco-oxidation/glycation.

PMID- 19401825
TI  - A meta-analysis of the Gamma nail and dynamic hip screw in treating
      peritrochanteric fractures.
AB  - The objective of this meta-analysis was to compare the fixation outcome of the
      Gamma nail and dynamic hip screw (DHS) in treating peritrochanteric fractures.
      Relevant randomised controlled studies were included, and the search strategy
      followed the requirements of the Cochrane Library Handbook. Methodological
      quality was assessed and data were extracted independently. Seven studies
      involving 1,257 fractures were included which compared the effect of the Gamma
      nail and DHS. The results showed a higher rate of postoperative femoral shaft
      fracture with the Gamma nail compared to the DHS [relative risk (RR): 7.27, 95%
      confidence interval (CI): 2.83-18.70, P < 0.0001] but no statistical differences
      in wound infection (RR: 1.02, 95% CI: 0.56-1.86), mortality (RR: 1.00, 95% CI:
      0.81-1.24), re-operation (RR: 1.64, 95% CI: 0.91-2.95) and walking independently
      after rehabilitation (RR: 0.89, 95% CI: 0.60-1.33). It seemed that there were no
      obvious advantages of the Gamma nail over the DHS in treating peritrochanteric
      fractures.

PMID- 19401826
TI  - Severe bullous skin lesions associated with Chikungunya virus infection in small
      infants.
AB  - INTRODUCTION: The aim of this study was to describe a pediatric case series of
      Chikungunya infection associated with extensive bullous skin lesions, a severe
      and unknown form of the disease, during the 2005-2006 outbreak in La Reunion
      Island. MATERIALS AND METHODS: Retrospective descriptive hospital-based study in
      children presenting blisters > or = 10% of total body surface area with
      laboratory-confirmed Chikungunya infection. RESULTS: Eight boys and five girls
      with a mean age of 3.4 months were included. Blistering began after an average of
      2 days after onset of fever and affected 21.5% (10% to 35%) of the total body
      surface area. Reverse transcription-polymerase chain reaction of blister fluid (n
      = 5) was positive with a mean viral load sometimes higher than in concurrent
      serum. Histopathologic examination (n = 10) showed intraepidermal blisters.
      Hospitalization and repeated dressing changes under general anesthesia were
      required. No death occurred. On follow-up, long term repigmentation was excellent
      with sometimes cosmetic sequelae. CONCLUSION: Chikungunya should be included in
      the differential diagnosis of febrile blistering dermatoses in small infants in
      epidemic areas.

PMID- 19401827
TI  - Bacteria associated with oak and ash on a TCE-contaminated site: characterization
      of isolates with potential to avoid evapotranspiration of TCE.
AB  - BACKGROUND, AIM, AND SCOPE: Along transects under a mixed woodland of English Oak
      (Quercus robur) and Common Ash (Fraxinus excelsior) growing on a
      trichloroethylene (TCE)-contaminated groundwater plume, sharp decreases in TCE
      concentrations were observed, while transects outside the planted area did not
      show this remarkable decrease. This suggested a possibly active role of the trees
      and their associated bacteria in the remediation process. Therefore, the
      cultivable bacterial communities associated with both tree species growing on
      this TCE-contaminated groundwater plume were investigated in order to assess the
      possibilities and practical aspects of using these common native tree species and
      their associated bacteria for phytoremediation. In this study, only the
      cultivable bacteria were characterized because the final aim was to isolate TCE
      degrading, heavy metal resistant bacteria that might be used as traceable inocula
      to enhance bioremediation. MATERIALS AND METHODS: Cultivable bacteria isolated
      from bulk soil, rhizosphere, root, stem, and leaf were genotypically
      characterized by amplified rDNA restriction analysis (ARDRA) of their 16S rRNA
      gene and identified by 16S rRNA gene sequencing. Bacteria that displayed distinct
      ARDRA patterns were screened for heavy metal resistance, as well as TCE tolerance
      and degradation, as preparation for possible future in situ inoculation
      experiments. Furthermore, in situ evapotranspiration measurements were performed
      to investigate if the degradation capacity of the associated bacteria is enough
      to prevent TCE evapotranspiration to the air. RESULTS AND DISCUSSION: Between
      both tree species, the associated populations of cultivable bacteria clearly
      differed in composition. In English Oak, more species-specific, most likely
      obligate endophytes were found. The majority of the isolated bacteria showed
      increased tolerance to TCE, and TCE degradation capacity was observed in some of
      the strains. However, in situ evapotranspiration measurements revealed that a
      significant amount of TCE and its metabolites was evaporating through the leaves
      to the atmosphere. CONCLUSIONS AND PERSPECTIVES: The characterization of the
      isolates obtained in this study shows that the bacterial community associated
      with Oak and Ash on a TCE-contaminated site, was strongly enriched with TCE
      tolerant strains. However, this was not sufficient to degrade all TCE before it
      reaches the leaves. A possible strategy to overcome this evapotranspiration to
      the atmosphere is to enrich the plant-associated TCE-degrading bacteria by in
      situ inoculation with endophytic strains capable of degrading TCE.

PMID- 19401828
TI  - Domain-and species-specific monoclonal antibodies recognize the Von Willebrand
      Factor-C domain of CCN5.
AB  - The CCN family of proteins typically consists of four distinct peptide domains:
      an insulin-like growth factor binding protein-type (IGFBP) domain, a Von
      Willebrand Factor C (VWC) domain, a thrombospondin type 1 repeat (TSP1) domain,
      and a carboxy-terminal (CT) domain. The six family members participate in many
      processes, including proliferation, motility, cell-matrix signaling,
      angiogenesis, and wound healing. Accumulating evidence suggests that truncated
      and alternatively spliced isoforms are responsible for the diverse functions of
      CCN proteins in both normal and pathophysiologic states. Analysis of the
      properties and functions of individual CCN domains further corroborates this
      idea. CCN5 is unique among the CCN family members because it lacks the CT-domain.
      To dissect the domain functions of CCN5, we are developing domain-specific mouse
      monoclonal antibodies. Monoclonal antibodies have the advantages of great
      specificity, reproducibility, and ease of long-term storage and production. In
      this communication, we injected mixtures of GST-fused rat CCN5 domains into mice
      to generate monoclonal antibodies. To identify the domains recognized by the
      antibodies, we constructed serial expression plasmids that express dual-tagged
      rat CCN5 domains. All of the monoclonal antibodies generated to date recognize
      the VWC domain, indicating it is the most highly immunogenic of the CCN5 domains.
      We characterized one particular clone, 22H10, and found that it recognizes mouse
      and rat CCN5, but not human recombinant CCN5. Purified 22H10 was successfully
      applied in Western Blot analysis, immunofluorescence of cultured cells and
      tissues, and immunoprecipitation, indicating that it will be a useful tool for
      domain analysis and studies of mouse-human tumor models.

PMID- 19401829
TI  - Normal growth and development in mice over-expressing the CCN family member
      WISP3.
AB  - Loss-of-function mutations in the gene WISP3 cause the autosomal recessive human
      skeletal disease Progressive Pseudorheumatoid Dysplasia, whereas mice with
      knockout mutations of Wisp3 have no phenotype. The lack of a phenotype in the
      Wisp3 knockout mice has constrained studies of the protein's in vivo function.
      Over-expression experiments in zebrafish indicated that WISP3 may function as a
      BMP and Wnt signaling modulator. To determine whether these biologic activities
      are retained in mice, we created two strains of transgenic mice that over-express
      WISP3 in a broad array of tissues. Despite strong and persistent protein over
      expression, the transgenic mice remained phenotypically indistinguishable from
      their non-transgenic littermates. Surprisingly, WISP3 contained in conditioned
      medium recovered from transgenic mouse primary kidney cell cultures was able to
      bind BMP and to inhibit BMP signaling in vitro. Factors that account for the
      difference between the in vitro and in vivo activities of WISP3 remain unknown.
      At present, the mouse remains a challenging model organism in which to explore
      the biologic function of WISP3. Summary of article. Transgenic mice that broadly
      over-express WISP3 were created to search for in vivo biologic activities, since
      mice that lack WISP3 were normal. Surprisingly, transgenic mice were also
      phenotypically indistinguishable from wild-type animals. The mouse is a
      challenging model organism in which to explore the biologic function of WISP3.

PMID- 19401830
TI  - Differential expression of Ki-67 and sex steroid hormone receptors between
      genders in peritoneal mesothelioma.
AB  - Gender influence on survival in mesothelioma has been observed in several large
      clinical series. However, this gender effect has not been investigated. Female
      patients often have less aggressive tumors and survive longer. However, few
      studies in the literature have explained the molecular basis of this finding.
      Understanding this difference at a molecular level may offer the hope of
      improving survival via hormonal manipulation.We investigate the expression of Ki
      67 and sex steroid receptors; estrogen receptors (ER), progesterone receptors
      (PR) and androgen receptors (AR) to elucidate any pathognomonic difference that
      characterize this gender difference. Positive expression of markers was observed
      in 95% (Ki-67), 80% (ER), 100% (PR) and 65% (AR) of patients. Expression of
      markers between gender showed a higher Ki-67 in males (M = 1.3%, F = 0.6%),
      higher estrogen receptor in females (M = 0.6%, F = 1.7%) and higher progesterone
      receptor in females (M = 1.0%, F = 1.4%). Twenty patients were treated with
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in our
      peritonectomy unit. Paraffin sections of the tumor specimens were retrieved for
      immunohistochemical analysis. The immunostaining was performed using monoclonal
      mouse anti-human antibodies on an autostainer (Autostainer Plus; Dako, Inc.). The
      intensity of the stains were quantified using the Image-Pro Plus (IPP) 4.5 (Media
      Cybernetics, Silver Spring, MD). For the first time, we demonstrate the presence
      of sex steroid receptors in peritoneal mesothelioma. Once the exact functional
      effects of these receptors are understood, the use of established therapeutic
      options that are clinically available to target the sex steroid pathway may
      become a reality.

PMID- 19401853
TI  - Satisfaction with life related to functionality in active elderly people.
AB  - INTRODUCTION: To study the relationship between the objective variables of
      functionality and degree of life satisfaction in elderly people with an active
      lifestyle. MATERIAL AND METHODS: The study took place using a sample of 340
      elderly people, aged 60-85, who were all leading an active life. The tests
      applied were: Satisfaction with Life Scale, Rivermead Behavioral Memory Test,
      Memory Failures Everyday, Geriatric Depression Scale, OARS social support
      subscale, COOP-WONCA physical dimension subscale and Siu and Reuben hierarchical
      scale for self-sufficiency. RESULTS: Statistical analyses were made using
      Pearson's correlations, with a significance level of p < 0.05 and p < 0.001
      between the objective variables and satisfaction with life level. The overall
      results show a negative correlation, that is, a paradox of well-being between the
      objective criteria of level of studies, memory level and self-sufficiency and the
      objective criterion of the level of life satisfaction. CONCLUSION: Proposals for
      intervention in elderly people's physical activity are needed, since reduced
      mobility could lead to a pathological pattern of life.

PMID- 19401831
TI  - Regulation of dendrite and spine morphogenesis and plasticity by catenins.
AB  - The appropriate regulation of dendrite, spine, and synapse morphogenesis in
      neurons both during and after development is critical for the formation and
      maintenance of neural circuits. It is becomingly increasingly clear that the
      cadherin-catenin cell adhesion complex, a complex that has been widely studied in
      epithelia, regulates neuronal morphogenesis. More interestingly, the catenins,
      cytosolic proteins that bind to cadherins, regulate multiple aspects of neuronal
      morphogenesis including dendrite, spine, and synapse morphogenesis and
      plasticity, both independent of and dependent on their ability to bind cadherins.
      In this review, we examine some of the more recent and exciting studies that
      implicate individual catenins in various aspects of neuronal morphogenesis and
      plasticity.

PMID- 19401854
TI  - Natural sex hormone cycles and gender differences in memory.
AB  - OBJECTIVE: To analyze gender differences in memory and the influence of the
      natural sex hormone cycles on it. METHOD: A total of 20 men and 19 women were
      assessed with memory tests two times coinciding with two hormonal phases of the
      diurnal cycle of testosterone in men or menstrual cycle in women. RESULTS: It was
      observed that women perform better than men in delayed verbal memory as well as
      in immediate and delayed object recall, and men in digit span. It was also found
      that there was a significant effect of the hormonal cycles on verbal working
      memory, immediate object recall and on the spatial component of visuoconstructive
      memory. Finally, hormonal cycles determine the existence and direction of gender
      differences in verbal working memory, delayed object recall and in the spatial
      component of visuoconstructive memory. CONCLUSIONS: Natural sex hormone cycles
      seem to influence gender differences in some measurements of memory.

PMID- 19401855
TI  - Mental illness and road safety.
AB  - INTRODUCTION: Psychiatric disorders, either due to their psychopathology or the
      drug treatments required, may lead to changes in perception, information
      processing and integration, and psychomotor activity which may disturb and/or
      interfere with the ability to drive safely. METHOD: This study assesses
      competence to drive in a sample of psychiatric outpatients, with a driver's
      license, who drove regularly. This ability was assessed with the accredited
      LNDETER 100 battery, an electronic assessment unit measurement, in different
      clinical situations. RESULTS: Only 24 of the 120 patients passed the four tests
      required to obtain or renew a driver's license, and 80% failed in at least one of
      the required tests. None of the patients studied had notified the traffic
      authorities or the examination centers that they had a psychiatric condition that
      could affect safe driving. No patient stopped driving, although 10% of them
      admitted that their ability to drive was somewhat deteriorated. CONCLUSIONS:
      Psychiatric patients with altered psychomotor performance should be a concern for
      psychiatrists and general practitioners regarding their competence to drive
      vehicles. Clinical, ethical and legal aspects of our findings are discussed.

PMID- 19401856
TI  - Hospital indicators by Regional Communities, 1980-2004 (Longitudinal analysis of
      morbidity indicators and hospital staffing in mental health).
AB  - INTRODUCTION: Comparative analysis by Spanish Regional Communities (RC) of
      indicators related to morbidity and staffing in psychiatric care hospital over a
      period of time (1980-2004) marked by the initiation and development of
      deinstitutionalization policies and handover of powers to RC. METHODOLOGY:
      Longitudinal study. Descriptive analysis of variables, broken down by RC, related
      to psychiatric morbidity (ICD-9, codes 290-319) and indicators of hospital
      staffing over a 25-year period. DATABASE SOURCE: Hospital Morbidity Survey, 1980
      2004 and Statistics for care facilities providing in-patient care regime, 1980
      2004. RESULTS: Differences between Regional Communities are substantial in all
      the analyzed variables: discharges, total and average stay, total and initial
      consultations, rate of psychiatrists in hospital care, number of beds and
      psychiatric hospitals. For all the Regional Communities as a whole, an increase
      is observed in hospital discharges, decrease of total and mean stays, notable
      increase of consultations, little increase in psychiatric staff in hospital care
      and stagnation in the decline of psychiatric hospitals and beds in operation in
      psychiatric hospital during the last period of time series and low increase in
      beds for the hospitals that are not classified as a psychiatric hospital.
      CONCLUSIONS: We found evidence of qualitatively different care models between
      Regional Communities and substantial changes in major indicators over time
      series.

PMID- 19401857
TI  - Psychometric validation of the Spanish version of the Patient-Doctor Relationship
      Questionnaire (PDRQ).
AB  - INTRODUCTION: The main aim of this study was to make a Spanish adaption of the
      international Patient-Doctor Relationship Questionnaire (PDRQ) that assesses the
      quality of patient-doctor relationship in Spanish patients admitted to an
      Internal Medicine Service under conditions of regular clinical practice. METHOD:
      A total of 188 adult patients of 6 Internal Medicine physicians from a University
      Hospital in downtown Madrid were analyzed. Sociodemographic and clinical
      variables were collected and the PDRQ Spanish version questionnaire was
      administered. RESULTS: Results showed excellent psychometric data on reliability,
      factorial, and construct validity. Furthermore, based on scientific literature,
      criteria validity was determined, considering continuity of care as external
      criteria. Results ratify previous data related to positive relation between
      quality of doctor-patient relation and continuity of care. CONCLUSIONS: The
      Spanish 13 item version of the PDRQ (CREM-P in Spanish) proved to be a valid
      instrument for assessing the quality of patient-doctor relation in adult
      patients, with clinical and research value.

PMID- 19401858
TI  - Residual symptoms in depression.
AB  - Despite successful response to therapy, subsyndromal depressive symptoms appear
      to be the rule in unipolar depression. Residual symptoms are present in more than
      30% of patients who respond to antidepressants, specifically in subjects with
      more severe initial illness. The most prevalent residual symptoms are affective,
      somatic, cognitive and sleep disturbance. It has been shown that such persistent
      symptoms are associated with a higher risk of relapse, chronicity and functional
      impairment; associated with neuroanatomical changes. It is important to consider
      the possibility of persistence subthreshold symptoms and look for new therapeutic
      strategies for improving the level of remission in the treatment of major
      depressive disorder.

PMID- 19401859
TI  - Cognitive-behavioral therapy for chronic psychosis.
AB  - Cognitive-behavioral therapy (CBT) has been used in recent years as an
      intervention for chronic psychoses, generally as a complement to the
      pharmacological treatment. This fact has motivated controlled studies that
      analyze the efficiency of this type of interventions. That is why this
      bibliographical review has aimed to analyze the most relevant studies up-to-date.
      Those works having a controlled and random design, that assured the requirements
      of reliability and validity, were included. The studies show encouraging results,
      because they support the efficiency of CBT as a measurement of treatment.
      Nevertheless, more investigations that support this information are still
      required.

PMID- 19401860
TI  - Conversive Gilles de la Tourette syndrome. A case report.
AB  - INTRODUCTION: Tourette's syndrome is a neurological disorder of genetic order
      that begins in childhood, being characterized by the presence of multiple phonic
      and motor tics. CLINICAL CASE: A male with previous dissociative and conversion
      psychopathology initiated motor and phonic tics in the adulthood in the context
      of several inter and intrapersonal conflicts beginning in childhood. No
      improvement was observed when drug treatment was established, there being partial
      response with psychotherapy oriented to coping with threatening situations.
      CONCLUSIONS: The psychopathology of the obsessive compulsive spectrum having a
      conversion and dissociative origin is an unusual phenomenon, this being observed
      in constitutionally predisposed subjects. Conversion tics are a nosologic
      challenge, given the fluctuations and exacerbations due to stress also manifested
      by their neurological homonyms. More specific criteria are necessary in order to
      optimize the diagnosis of this "psychogenic movement disorder".

PMID- 19401861
TI  - Pathological gambling and hypersexuality due to dopaminergic treatment in
      Parkinson' disease.
AB  - INTRODUCTION: Prevalence of psychiatric disorders in patients suffering from
      Parkinson's disease varies from 12 to 90%. The most common disorder in the
      natural evolution of Parkinson's disease is depression. However, episodes of
      psychosis and hypomania are related to treatment with L-dopa and dopaminergic
      agents. Other recognized, although less frequent, psychiatric disorders are
      hypersexuality and development of certain addictive behaviors, which is
      compulsive gambling and overdosing of anti-Parkinson agents. CLINICAL CASE: A
      case is presented of a male patient diagnosed with Parkinson's Disease at an
      early age who was treated with L-dopa and a combination of dopaminergic agents.
      During the course of his evolution he manifested symptoms of hypersexuality and
      pathological gambling which were unrelated to psychotic or mood changes.
      CONCLUSIONS: A number of hospital admissions were needed into order to detect a
      pattern of abusive consumption of L-dopa as the main factor behind his behavior
      changes. The possibility of overdosage of L-dopa and dopaminergic drugs should be
      considered when there is pathological gambling conduct and/or hypersexuality,
      without psychotic or accompanying affective symptoms, in a male who develops
      Parkinson's disease at an early age and who undergoes treatment with these drugs
      and manifests motor fluctuations and dyskinesias. Early detection of the presence
      of these alterations, included within those described as "dopaminergic
      dysregulation syndrome", would allow for an early intervention on the cause
      behind them and would hence avoid the possible medical and social complications.

PMID- 19401862
TI  - The vascularization of the human cochlea: its historical background.
AB  - The history of vascularization of the human cochlea began with the first
      anatomical description of the cochlea in the 16th century. Three different
      periods are recognizable in the development of knowledge concerning this subject:
      the macroscopic period, with the description of the structure of the cochlea from
      the 16th to the 19th century; the microscopic period, with the description of the
      part of the organ of Corti in the 19th century; and the injection period, with
      the description of the fine vascularization of the cochlea in the 20th century.
      Various techniques were used during these three periods, which will be presented
      here, using only original references. This historical study reveals the ingenuity
      of the researchers in using different aspects of technological progress to
      enhance their performance in research.

PMID- 19401863
TI  - Are there age differences in the executive component of working memory? Evidence
      from domain-general interference effects.
AB  - Young and older adults performed verbal and spatial storage-only and storage-plus
      processing working memory tasks while performing a secondary finger tapping task,
      and the effects on both the maximum capacity (measured as the longest series
      correct) and the reliability (measured as the proportion of items correct) of
      working memory were assessed. Tapping tended to produce greater disruption of
      working memory tasks that place greater demands on executive processes (i.e.,
      storage-plus-processing tasks compared to storage-only span tasks). Moreover,
      tapping produced domain-general interference, disrupting both verbal and spatial
      working memory, providing further support for the idea that tapping interferes
      with the executive component of the working memory system, rather than domain
      specific maintenance processes. Nevertheless, tapping generally produced
      equivalent interference effects in young and older adults. Taken together, these
      findings are inconsistent with the hypothesis that age-related declines in
      working memory are primarily attributable to a deficit in the executive
      component.

PMID- 19401864
TI  - How families in Japan view the disclosure of terminal illness: a study of
      iatrogenic HIV infection.
AB  - Physicians in Japan typically do not disclose diagnoses of terminal illnesses to
      patients, in deference to the wishes of family members. Nonetheless, some
      evidence indicates that relatives of patients with iatrogenic HIV infection would
      prefer patient disclosure. We collected survey data from 314 family members in
      225 households of hemophiliac patients who died from illnesses related to
      iatrogenic HIV infection in order to examine current attitudes toward patient
      disclosure in Japan. Family members reported that the diagnosis of iatrogenic HIV
      infection was disclosed to the patient by the primary physician in 32.8% of
      cases, by the family in 8.3% of cases, and not disclosed in 26.4% of cases. The
      majority of families indicated that the timing of the physician's disclosure
      occurred too late. Multivariate analysis indicated that families wished that
      patients had been informed of the diagnosis, despite the stigma associated with
      HIV in Japan. Furthermore, many families blamed the physician for the infection
      and fatality in those cases in which the physician did not convey feelings of
      regret. These results have important clinical ramifications to the practice of
      disclosing terminal diagnoses in Japan.

PMID- 19401865
TI  - Factors associated with adherence to highly active antiretroviral therapy in
      homeless or unstably housed adults living with HIV.
AB  - The aim of this study is to investigate adherence to highly active antiretroviral
      therapy (HAART) in persons living with HIV/AIDS (PLWHA) who are homeless or
      unstably housed. We evaluated homeless or unstably housed PLWHA (n=644) in three
      US cities were enrolled in the Housing and Health Study. Using baseline data and
      controlling for gender, race, age, and education, we examined associations
      between self-reported two- and Seven-day adherence and access to healthcare,
      mental health, substance use, and attitudes toward HIV medical therapy. Of the
      644 participants, 358 (55%) were currently on HAART. For two-day adherence, 280
      (78%) reported missing no prescribed doses (100% adherence), and for seven-day
      adherence, 291 (81%) reported > or =90% adherence. Logistic regression analyses
      indicated being younger, not having health insurance, and drug use were
      associated with missing > or =1 dose over the past two days. Scoring lower on SF
      36 mental component summary scale and having greater risk of depression (CES-D)
      and stress (Perceived Stress Scale) were associated with poorer adherence for
      both two- and seven-day outcomes. Negative attitudes toward HIV treatment were
      also associated with lower adherence. Adherence to HIV medications in this
      population is similar to other groups. Coexisting problems of access to
      healthcare, higher risk of mental health problems, along with poorer attitudes
      toward treatment are associated with increased likelihood of missing doses.
      Comprehensive models of HIV care that include a continuum of medical and social
      services are essential for treating this population.

PMID- 19401866
TI  - Factors associated with HIV testing among sexually active South African youth
      aged 15-24 years.
AB  - HIV infection is high among South African youth but most report being unaware of
      their HIV status. We explored the correlates of HIV testing using data from youth
      aged 15-24 years old who reported being sexually experienced during a national
      survey conducted in South Africa in 2003 (N=7665). Among sexually experienced
      youth, 32.7% of females and 17.7% of males reported having been tested for HIV.
      In multivariable analysis, ever being pregnant (OR = 2.97; 95% CI 2.36-3.73),
      ever starting a conversation about HIV/AIDS (OR = 1.29; 95% CI 1.0-1.65) and
      urban residence (OR = 2.0; 95% CI 1.58-2.52) were independent correlates of HIV
      testing among sexually experienced females. Among sexually experienced males, HIV
      positive status (OR = 1.76; 95% CI 1.14-2.73), personally knowing someone that
      died of AIDS (OR = 1.68; 95% CI 1.14-2.47), being aged 20-24 years (OR = 1.56;
      95% CI 1.10-2.22) and having completed high school (OR = 1.58; 95% CI 1.17-2.12)
      were independent correlates of HIV testing. The following factors were
      significantly associated with HIV testing among both men and women; ever talking
      to parents about HIV/AIDS, ever participating in a loveLife programme, a higher
      frequency of visits to a clinic in the past 12 months and non-black race
      (p<0.05). There is a need to better understand the correlates of HIV testing to
      ensure that adolescent HIV prevention programmes actively promote HIV testing
      among this group. Specific attention needs to be paid to young women who do not
      access antenatal care and young men who are less regular users of routine
      clinical care. Communication is a significant predictor of having tested for HIV
      and should be encouraged with parents and through intervention programmes for
      adolescents. Finally, specific attention must be paid to increasing access to HIV
      testing for at-risk adolescents in rural communities.

PMID- 19401867
TI  - The influence of symptom experiences and attributions on adherence to highly
      active anti-retroviral therapy (HAART): a six-month prospective, follow-up study.
AB  - OBJECTIVE: To examine changes in individuals' experiences of symptoms over the
      first six months of taking highly active anti-retroviral therapy (HAART) and to
      assess the impact of symptom experiences and attributions on adherence to HAART.
      METHODS: A prospective study where consecutive HIV positive individuals
      initiating HAART completed validated questionnaires assessing their experiences
      of symptoms, depression, beliefs about HAART and adherence, before starting
      treatment and after one, three and six months of treatment. RESULTS: Rates of low
      (<95%) adherence to HAART increased over time (p<0.001). Overall, the number of
      HIV or HAART-related symptoms reported did not change significantly over follow
      up. However, symptom experiences differed between those reporting high (> or
      =95%) adherence and those reporting low adherence. Individuals reporting high
      adherence experienced a decrease in symptoms they attributed to HIV (p<0.05), and
      a decrease in the symptoms they attributed to HAART-side effects (p<0.05) over
      time. This decrease in symptoms over time was not seen among individuals
      reporting low adherence. A lack of symptomatic improvement was associated with
      increasing doubts about the continued necessity for HAART (p<0.05). CONCLUSIONS:
      The findings suggest that adherence to HAART is influenced by individuals'
      experiences of both HIV and HAART-related symptoms. Patients who experience
      persistent symptoms while on HAART may begin to doubt their continued need for
      treatment and respond by missing doses. These findings have implications for the
      development of evidence-based interventions to increase adherence.

PMID- 19401868
TI  - Influencing factors for seeking HIV voluntary counseling and testing among
      tuberculosis patients in Cambodia.
AB  - We explored the factors influencing voluntary counseling and testing (VCT)
      utilization among tuberculosis patients attending two referral hospitals in
      Cambodia. We conducted face-to-face interviews using a structured questionnaire.
      We compared HIV/AIDS knowledge, HIV testing attitudes, risks for exposure to HIV,
      and AIDS stigma between VCT users and non-users. Compared to VCT non-users, VCT
      users had significantly higher risks for HIV and were more likely to have used
      condoms. Regarding stigma, VCT non-users demonstrated significantly greater AIDS
      stigmatizing beliefs compared to VCT users. To increase VCT utilization among TB
      patients, we need effective strategies to reduce AIDS stigma among them.
      Moreover, initiation of routine HIV testing in TB facilities might be another
      effective solution.

PMID- 19401873
TI  - The effects of surgical rapid maxillary expansion (SRME) on vowel formants.
AB  - The objective of this study was to investigate the effect of surgical rapid
      maxillary expansion (SRME) on vowel production. The subjects included 12
      patients, whose speech were considered perceptually normal, that had undergone
      surgical RME for expansion of a narrow maxilla. They uttered the following
      Turkish vowels, ([a], [e], [dotless i], [i], [o], [oe], [u], [y]), in isolation
      before and after the maxillary expansion. These samples were recorded for
      acoustical analysis. The fundamental frequencies (F0) and the frequencies and
      bandwidths of the first two formants (F1 and F2) of the vowels were measured
      using the Multi-Speech programme (Kay Elemetrics). Statistical analysis revealed
      that the second formant frequency (F2) and bandwidth values in the vowel [i] and
      [oe] were lowered after maxillary expansion (p<.05). Surgical RME induced the
      decrease in the second formant of the [i] and [oe] vowels by affecting the size
      of the anterior oral cavity, however the influence was too small to cause any
      differences in the acoustic properties of the other vowels.

PMID- 19401874
TI  - PAX3 across the spectrum: from melanoblast to melanoma.
AB  - The PAX3 transcription factor is critical for the proper development of neural
      crest lineages including melanocytes. These cells show continued PAX3 expression
      from formation to differentiation. While many expression, misexpression and
      mutation studies clarify the importance of PAX3 in melanocyte development, less
      well understood, and more perplexing, is the continued PAX3 expression in the
      adult skin. In this article we explore the multiple roles of PAX3 in melanocyte
      genesis, and draw on evidence from expression in developing melanoblasts, adult
      melanocytes and melanocyte stem cells. From this, we present a more encompassing
      theory that PAX3 is a key regulator of the myriad steps in melanocytic cell
      determination. These roles may be accomplished by differential association with
      cofactors, via alternate transcripts or posttranslational protein
      modification(s). In light of the plethora of information gleaned from development
      we then consider its roles in melanoma and provide here a comprehensive
      consideration of the significance of PAX3 expression in melanoma. PAX3 and Pax3
      indicate human and mouse transcription factors respectively.

PMID- 19401875
TI  - Ferric reducing ability of tears in healthy subjects-diurnal variation and
      dependence on defined demographic data.
AB  - PURPOSE: The assay of the ferric reducing ability of tears (FRAT) can be useful
      for monitoring ocular antioxidant capacity in clinical settings. FRAT diurnal
      variation was evaluated in healthy subjects and its relation with age, sex, body
      mass index, and ferric reducing ability of plasma (FRAP) were studied. MATERIAL
      AND METHODS: FRAT of 10-microl tear samples collected with capillary tubes from
      68 healthy subjects (age 10 to 92 yrs, 46 women, 22 men) were measured after 0,
      3, 5, and 10 min of incubation with Fe(3 +). FRAT diurnal variation was estimated
      in 11 subjects, with tear samples collected every 4 hr during the day. Comparison
      of FRAT versus FRAP was determined in 20 subjects. RESULTS: Mean FRAT after 10
      min incubation reached 207.7 +/- 136.8 micromol/l. No differences were found
      between FRAT of men and women. Only donor age correlated with FRAT (rho = 0.40, p
      < 0.01). Subjects <or= 59 years had lower FRAT levels than those age > 59 yrs
      (179.4 +/- 95.4 versus 237.2 +/- 151.7 micromol/l, p < 0.01). For all
      investigated times of incubation, FRAT was approximately two times lower than
      FRAP (p < 0.01). FRAT revealed diurnal variation, with the highest value at 08:00
      hours, upon awakening. CONCLUSION: The significance of age-matched controls and
      the specific time of the day for tears collection should be considered in the
      trial design and investigations with FRAT as a marker of the ocular antioxidant
      defense system.

PMID- 19401876
TI  - A novel scraping cytology score system (SCSS) grades inflammation in dry eye
      patients.
AB  - PURPOSE: We propose a conjunctival Scraping Cytology Scoring System (SCSS) as a
      reliable method to diagnose and score ocular surface inflammation in dry eye.
      METHODS: Twenty normal subjects and 46 patients with dry eye of various
      severities were included in the study. Clinical signs were scored 1-4; an Ocular
      Surface Disease Index (OSDI) questionnaire was used to grade subjective symptoms.
      Concentrations of serum albumin and interleukin-6 (IL-6) in tears were evaluated.
      Scraped conjunctival cytology samples were processed and examined with light
      microscopy. The number of inflammatory cells was staged and sub-scores were
      assigned. SCSS resulted from their sum and ranged from 0-12. Statistical
      evaluation was performed by applying the unpaired Student's t-test and the
      Spearman's correlation test (significance p < 0.05). SCSS was also analyzed for
      sensitivity, specificity, ROC curves, likelihood ratio LR+, positive (PPV)
      predictive value. RESULTS: SCSS was positively correlated to clinical sign score,
      OSDI score, exudated serum albumin, and IL-6 in either control (Spearman's
      correlation test always p < 0.05) and in dry eye patients (respectively, p <
      0.0001, p < 0.01, p < 0.05, and p < 0.0001). SCSS >or= 4 was selected as the cut
      off value for moderate dry eye (LR+ 10,9; PPV 22,5), SCSS >or= 9 was selected as
      the cut-off value for severe dry eye (LR+ 15,6; PPV 26,2). CONCLUSIONS: SCSS can
      be applied in any trained laboratory. It is correlated with clinical signs and
      symptoms, and it shows a diagnostic performance to grade inflammation in dry eye,
      comparable to more expensive cytokine assay.

PMID- 19401877
TI  - The effects of dexamethasone on the Na,K-ATPase activity and pump function of
      corneal endothelial cells.
AB  - PURPOSE: The Na(+)- and K(+)-dependent ATPase (Na,K-ATPase) expressed in the
      basolateral membrane of corneal endothelial cells plays an important role in the
      pump function of the corneal endothelium. We investigated the possible role of
      dexamethasone in the regulation of Na,K-ATPase activity and pump function in
      corneal endothelial cells. METHODS: Confluent monolayers of mouse corneal
      endothelial cells were exposed to dexamethasone. ATPase activity of the cells was
      evaluated by spectrophotometric measurement of phosphate released from ATP with
      the use of ammonium molybdate, with Na,K-ATPase activity being defined as the
      portion of total ATPase activity sensitive to ouabain. Pump function of the cells
      was measured with the use of an Ussing chamber, with the pump function
      attributable to Na,K-ATPase activity being defined as the portion of the total
      short-circuit current sensitive to ouabain. Western blot analysis was examined to
      measure the expression of the Na,K-ATPase alpha(1)-subunit. RESULTS:
      Dexamethasone (1 or 10 microM) increased the Na,K-ATPase activity and pump
      function of the cultured cells. These effects of dexamethasone were blocked by
      cycloheximide, a protein synthesis inhibitor. Western blot analysis also
      indicated that dexamethasone increased the expression of the Na,K-ATPase alpha(1)
      subunit, whereas it decreased the expression of the phospho-Na,K-ATPase alpha(1)
      subunit. CONCLUSIONS: Our results suggest that dexamethasone stimulates Na,K
      ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone
      activation in these cells is mediated by Na,K-ATPase synthesis and increase in an
      enzymatic activity by dephosphorylation of Na,K-ATPase alpha(1)-subunits.

PMID- 19401878
TI  - Chloral hydrate anesthesia and lens opacification in mice.
AB  - PURPOSE: To study the effect of chloral hydrate in the eye lens in mice. METHODS:
      We instilled tropicamide in the eyes of two groups of eight 129 strain wild-type
      mice and injected chloral hydrate intraperitoneally (400 mg/kg). A drop of
      hypromellosum solution was additionally instilled in the eye of the second group
      to reduce corneal dehydration. The lens was inspected at several time intervals
      with a standard slit lamp biomicroscope after the injection. RESULTS: No lens
      opacification was found in any animal after the topical administration of
      tropicamide. On the contrary, the intraperitoneal administration of chloral
      hydrate produced lens opacification in both groups of animals. CONCLUSIONS: We
      show that chloral hydrate, when used intraperitoneally, induces acute and
      reversible lens opacification in all animals. In addition, we found that
      instillation of hypromellose solution does not prevent the lens opacification
      caused by chloral hydrate injection. We hypothesized some plausible explanations
      for these findings.

PMID- 19401879
TI  - Characteristics of ethylnitrosourea-induced cataracts.
AB  - PURPOSE: This study analyzed genes associated with the morphology and regulation
      of ethylnitrosourea (ENU)-induced cataract mouse. MATERIALS AND METHODS:
      Immunohistochemistry analysis using anti-crystallins and PCNA antibody revealed
      that the localization pattern of these specific markers differed between the
      cataractous and wild-type lens epithelium. Two-dimensional electrophoresis and
      microarray techniques were used to identify the proteins and genes related to ENU
      induced cataract. RESULTS: A novel ENU-induced mutation in the mouse led to
      nuclear and cortical opacity of the eye lens at 5 weeks postnatal. This cataract
      phenotype was similar to that of the zonular-pulverulent type of human cataract.
      Crystallin proteins and gap-junction genes have relations to the formation of
      cataract. CONCLUSIONS: Together, the results suggest that various proteins affect
      the formation and specific phenotypes of ENU-induced cataract mouse.

PMID- 19401880
TI  - 24-hour intraocular pressure and blood pressure levels with latanoprost/timolol
      fixed combination versus timolol.
AB  - PURPOSE: To evaluate 24-hr intraocular pressure (IOP) and blood pressure (BP)
      with timolol or latanoprost/timolol fixed combination (LTFC). METHODS: Patients
      with primary open-angle glaucoma or ocular hypertension with normal blood
      pressure were randomized to LTFC, dosed each evening, or timolol dosed twice
      daily in a cross-over design for 8 weeks and the opposite medicine for 8 weeks.
      IOP was measured at 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours in the
      sitting position with Goldmann applanation tonometry and BP monitoring every 30
      min while awake and every hour while asleep at the end of each 8-week treatment
      period. RESULTS: Twenty-nine patients had a 24-hr baseline IOP of 26.3 +/- 2.5
      mmHg, systolic BP (SBP) of 121.4 +/- 12.4 mmHg, diastolic BP (DBP) 72.9 +/- 7.1
      mmHg, and ocular perfusion pressure (OPP) of 33.9 +/- 5.7 mmHg. No statistical
      differences were found between untreated and treated 24-hr SBP, DBP, mean BP
      (MBP), heart rate, or nocturnal BP dipping status with either medication. LTFC
      lowered IOP more at each timepoint compared to timolol (difference between
      treatments 2.7 mmHg, p = 0.0002). CONCLUSIONS: Neither timolol or evening-dosed
      LTFC reduced SBP, DBP, MBP, OPP, or increased nocturnal dipping. LTFC was more
      effective than timolol in decreasing IOP.

PMID- 19401881
TI  - Distribution of photopic pupil diameter in the Tehran eye study.
AB  - PURPOSE: To determine the photopic pupil diameter and its determinants in a
      sample derived from a population-based survey in Tehran. METHODS: In a cross
      sectional study with a stratified random cluster sampling approach, 410 people
      age 14 years and over were selected from those residing in the first four
      municipality districts of Tehran after applying exclusion criteria, and 800 eyes
      (399 right eyes and 401 left eyes) were examined with the Orbscan II. The main
      outcome measure was the mean pupil diameter under photopic conditions, and
      possible correlations with potential determinants were evaluated through linear
      regression analyses. The design effect of a cluster sampling approach was
      observed and adjusted for. RESULTS: The mean age of the participants was 40.6 +/-
      16.8 years and 38.8% were male. The mean photopic pupil diameter (PPD) was 3.70
      mm (range 2.30 to 5.10; 95% confidence interval (CI) 3.62 to 3.78). The mean PPD
      was 3.67 mm (95% CI, 3.54 to 3.81) in men and 3.72 mm (95% CI, 3.63 to 3.81) in
      women (p = 0.481). There was a significant reduction of 0.021 mm in PPD per year
      of aging (r = -0.49, p < 0.001). There was also a significant inverse correlation
      between PPD and spherical equivalent (r = -0.12, p = 0.034), while there was 0.66
      mm increase in PPD with every 1.0-mm increase in the anterior chamber depth (ACD)
      (p < 0.001). Anisocoria, defined as a pupil diameter difference more than 0.4 mm
      between two eyes, was observed in 12.2% of the study population. CONCLUSION:
      While the mean PPD measured with the Orbscan II was 3.70 mm in a sample derived
      from a population-based survey in Tehran, the scarcity of similar studies and
      reports concerning the pupil diameter measured with the Orbscan II makes it
      difficult to draw eligible comparisons. The pupil diameter has reverse
      correlations with age and spherical equivalent, a direct correlation with ACD,
      but is not correlated with gender.

PMID- 19401882
TI  - Expression of the multi-drug resistance proteins and the pregnane X receptor in
      treated and untreated retinoblastoma.
AB  - PURPOSE: To compare the expression of pregnane xenobiotic receptor and certain
      multi-drug resistance proteins in retinoblastoma. METHODS: Using tissue
      microarray analyses, we studied 62 pathology specimens for expression of pregnane
      xenobiotic receptor, multi-drug resistance 1/P glycoprotein, multi-drug
      resistance proteins 1, 2, and 4, and breast cancer resistant protein. RESULTS:
      Comparing tumors treated with primary enucleation with tumors treated with
      chemotherapy and/or radiation showed no significant differences in the expression
      of multi-drug resistance proteins or pregnane xenobiotic receptor. Pregnane
      xenobiotic receptor was correlated with multi-drug resistance protein 2
      expression (p < 0.001). CONCLUSION: Our results indicate selection, rather than
      induction, of chemoresistant cells as a cause for treatment failure in managing
      retinoblastoma with primary systemic chemotherapy.

PMID- 19401884
TI  - Lentivirus-mediated sFlt-1 gene fragment transfer suppresses retinal
      neovascularization.
AB  - PURPOSE: sFlt-1, a soluble secreted variant of the vascular endothelial growth
      factor (VEGF) receptor-1 that possesses only its extracellular domain, is a
      specific endogenous inhibitor of VEGF, which is involved in retinal
      vasculogenesis. Our objective was to determine the effects of various sFlt-1 gene
      fragments on retinal neovascularization in vivo using a murine oxygen-induced
      ischemic retinopathy (OIR) model. METHODS: Lentiviral expression plasmids
      carrying the sFlt-1 gene fragments containing Ig-like domains 2nd-3rd and 2nd-4th
      were constructed. Retinal neovascularization was induced by exposing neonatal
      mice to hyperoxia (75% O(2)) on post-natal day 7 (P7) and then returning them to
      normoxia (21% O(2)) on P12. After sFlt-1 gene fragment transfer, retinal
      neovascularization was examined via fluorescein angiography and hematoxylin-eosin
      staining. In addition, changes in the expression of VEGF and its functional
      receptor KDR/Flk-1 were examined via Western blotting and immunohistochemistry.
      RESULTS: Lenti.sFlt-1(2-3) and lenti.sFlt-1(2-4) both significantly inhibited
      neovascularization in OIR mice. Retinas from mice treated with lenti.sFlt-1(2-3)
      demonstrated a more marked reduction in neovascular cell nuclei compared with
      mice treated with lenti.sFlt-1(2-4), and these results were confirmed by
      fluorescence angiography. Gene transfer showed a very weak effect on VEGF protein
      expression, whereas KDR/Flk-1 protein expression was strongly inhibited,
      particularly in mice treated with lenti.sFlt-1(2-3). CONCLUSIONS: Lentivirus
      mediated sFlt-1 gene transfer significantly inhibits retinal neovascularization
      in OIR. Thus, sFlt-1 gene transfer may represent a potential therapeutic strategy
      for preventing retinal neovascularization.

PMID- 19401883
TI  - Case report: autofluorescence imaging and phenotypic variance in a sibling pair
      with early-onset retinal dystrophy due to defective CRB1 function.
AB  - PURPOSE: To phenotype two siblings with autosomal recessive early-onset retinal
      dystrophy due to CRB1 mutations. METHODS: Autofluorescence (AF) imaging, high
      resolution optical coherence tomography (OCT), and full-field electroretinography
      (ERG) were performed. The results of DNA sequencing from polymerase chain
      reaction (PCR) products of the CRB1 gene were obtained from hospital records.
      RESULTS: Two siblings, 14 years old and 17 years old, were compound heterozygotes
      for 749 del Ser and C948Y mutations in the gene encoding CRB1. AF imaging
      documented the preservation of retinal pigment epithelium (RPE) along the
      arterioles. High-resolution OCT showed abnormally thick retinae with increased
      lamination. CONCLUSION: Leber congenital amaurosis caused by CRB1 is a unique
      form of early-onset retinal dystrophy because it spares the para-arteriolar RPE
      and causes abnormal retinal lamination with thickening. These findings,
      detectable with AF imaging and high-resolution OCT, can be combined with
      electrophysiology and genetic testing to molecularly classify retinal
      degenerations efficiently.

PMID- 19401885
TI  - Fibrae medullares in the retina of the RD mouse: a case report.
AB  - PURPOSE: A rare finding of fibrae medullares in the mouse eye is presented in an
      animal suffering from retinal degeneration. MATERIAL AND METHODS: Numerous eyes
      from different mouse strains were screened for myelinated fibres in the retina.
      Light and electron microscopy was used to document a single case in a rd mouse.
      RESULTS: Myelinated fibres were found in the inner retina but not continuous with
      the optic nerve. CONCLUSION: Even in this highly degenerated retina the potency
      of the optic nerve fibres to become myelinated still remained. The source of the
      appropriate glia cells is discussed.

PMID- 19401887
TI  - Proteomic profiling of human embryonic stem cell-derived microvesicles reveals a
      risk of transfer of proteins of bovine and mouse origin.
AB  - BACKGROUND AIMS: Microvesicles (MV) shed from the plasma membrane of eukaryotic
      cells, including human embryonic stem cells (hESC), contain proteins, lipids and
      RNA and serve as mediators of cell-to-cell communication. However, they may also
      contain immunogenic membrane domains and infectious particles acquired from
      xenogenic components of the culture milieu. Therefore, MV represent a potential
      risk for clinical application of cell therapy. METHODS: We tested the ability of
      hESC and their most commonly used feeder cells, mouse embryonic fibroblasts
      (MEF), to produce MV. We found that hESC are potent producers of MV, whereas
      mitotically inactivated MEF do not produce any detectable MV. We therefore
      employed a combined proteomic approach to identify the molecules that constitute
      the major components of MV from hESC maintained in a standard culture setting
      with xenogenic feeder cells. RESULTS: In purified MV fractions, we identified a
      total of 22 proteins, including five unique protein species that are known to be
      highly expressed in invasive cancers and participate in cellular activation,
      metastasis and inhibition of apoptosis. Moreover, we found that hESC-derived MV
      contained the immunogenic agents apolipoprotein and transferrin, a source of
      Neu5Gc, as well as mouse retroviral Gag protein. CONCLUSIONS: These findings
      indicate that MV represent a mechanism by which hESC communicate; however, they
      also serve as potential carriers of immunogenic and pathogenic compounds acquired
      from environment. Our results highlight a potential danger regarding the use of
      hESC that have previously been exposed to animal proteins and cells.

PMID- 19401891
TI  - Sport, leisure and ergonomics VI.

PMID- 19401889
TI  - Development and validation of a biodynamic model for predicting multi-finger
      movements in cylinder-grasping tasks.
AB  - This article describes the development and validation of a model for predicting
      multi-finger movements in grasping activities. The model builds upon a newly
      proposed approach that incorporates forward dynamics and a system identification
      procedure, and is amenable to empirical tests. A database of multi-fingered
      grasping movements performed by 28 subjects was established and divided into four
      sets, one for model development and three for model validation. In the
      development phase, model parameter values were estimated by the iterative system
      identification procedure through a physics-based heuristic algorithm. The
      estimated parameter values were then statistically synthesised and integrated
      into the prediction model. In the validation phase, the model was applied to
      three novel datasets containing different grasping movements involving objects of
      varied sizes and different subjects. The results demonstrated the model's ability
      to predict hand prehensile movements with error magnitudes comparable to the
      inter-person variability in performing such movements. New insights into the
      control of multi-fingered hand prehensile movements at the systems and joint
      levels emerged from the model development and validation process. The current
      study contributes to building a foundation for long-term development of realistic
      biodynamic simulation of multi-finger hand movements. Such simulation
      capabilities will aid in design of hand-operated tools, devices or hand-intensive
      work for proactive ergonomics and in evaluation as well as treatment of
      functional impairment of the hand.

PMID- 19401892
TI  - A practical cooling strategy for reducing the physiological strain associated
      with firefighting activity in the heat.
AB  - The aim of this study was to establish whether a practical cooling strategy
      reduces the physiological strain during simulated firefighting activity in the
      heat. On two separate occasions under high ambient temperatures (49.6 +/- 1.8
      degrees C, relative humidity (RH) 13 +/- 2%), nine male firefighters wearing
      protective clothing completed two 20-min bouts of treadmill walking (5 km/h, 7.5%
      gradient) separated by a 15-min recovery period, during which firefighters were
      either cooled (cool) via application of an ice vest and hand and forearm water
      immersion ( approximately 19 degrees C) or remained seated without cooling
      (control). There was no significant difference between trials in any of the
      dependent variables during the first bout of exercise. Core body temperature
      (37.72 +/- 0.34 vs. 38.21 +/- 0.17 degrees C), heart rate (HR) (81 +/- 9 vs. 96
      +/- 17 beats/min) and mean skin temperature (31.22 +/- 1.04 degrees C vs. 33.31
      +/- 1 degrees C) were significantly lower following the recovery period in cool
      compared with control (p < 0.05). Core body temperature remained consistently
      lower (0.49 +/- 0.02 degrees C; p < 0.01) throughout the second bout of activity
      in cool compared to control. Mean skin temperature, HR and thermal sensation were
      significantly lower during bout 2 in cool compared with control (p < 0.05). It is
      concluded that this practical cooling strategy is effective at reducing the
      physiological strain associated with demanding firefighting activity under high
      ambient temperatures.

PMID- 19401893
TI  - Reproducibility of ratings of perceived exertion soon after myocardial
      infarction: responses in the stress-testing clinic and the rehabilitation
      gymnasium.
AB  - The purpose of this study was to compare ratings of perceived exertion (RPE;
      Borg's 6-20 scale) at the same exercise intensity, between a standard exercise
      electrocardiogram (ECG) treadmill stress test (exECG) and two subsequent bouts of
      treadmill exercise in a cardiac rehabilitation gymnasium. Eleven patients (mean
      +/- s) 60.8 +/- 6.1 years performed an exECG within 12.1 +/- 7.5 d after
      myocardial infarction (MI) and commenced their first exercise-based
      rehabilitation session (gym-1), which included the use of a motorised treadmill,
      within 5.0 +/- 1.3 d after the exECG. A second gym session (gym-2) was performed
      within 4.2 +/- 1.3 d of gym-1. Gym-1 and gym-2 treadmill exercise was performed
      at an intensity that equated to the penultimate testing stage of exECG, and RPE
      and heart rate were compared at this level between the three sessions of testing.
      The mean work rate at the penultimate testing stage of the exECG was 6.0 +/- 1.0
      metabolic equivalents; approximately 67% of peak work rate. The RPE at this work
      rate during exECG, gym-1 and gym-2 were 15.8 +/- 2.7, 13.3 +/- 3.4 and 13.0 +/-
      3.6, respectively. A repeated measures ANOVA revealed these RPE responses to be
      significantly different (F (2, 20) = 9.8; p = 0.001). Post-hoc Bonferroni
      corrected pairwise t-tests showed significant differences (p < or = 0.008)
      between exECG and gym-1 and exECG and gym-2 but not between gym-1 and gym-2.
      There was no significant difference in heart rate between the three testing
      sessions (p = 0.076) but it showed signs of a similar trend to RPE. The intra
      participant agreement in RPE between gym-1 and gym-2 was substantial; intraclass
      correlation coefficient (ICC(2,1)) = 0.85 (p < 0.001) and in all but one
      participant, RPE differed by < or =2 scale points. The RPE responses during
      standardised exECG treadmill testing, in patients soon after MI, are inflated
      compared to responses at the same treadmill work rate during subsequent cardiac
      rehabilitation exercise sessions. Caution is advised in using RPE taken from an
      initial exECG to guide physical activity in MI patients, but introducing RPE at
      this point contributes to its subsequent reliable use.

PMID- 19401895
TI  - Optimising speed and energy expenditure in accurate visually directed upper limb
      movements.
AB  - Traditional models of speed-accuracy relations and limb control are steady-state
      models that fail to consider the learning history and strategic approach of the
      performer. Work from this laboratory indicates that a performer adjusts his/her
      behaviour from trial-to-trial to optimise not only the speed and accuracy of
      performance, but also energy expenditure. Because some errors have greater
      temporal and energy costs than others, most performers execute movements that are
      prepared such that potential errors are of minimal expense. The trajectories and
      subsequent endpoint distributions of rapid aiming movements depend on advance
      knowledge about the availability of afferent information for online control, as
      well as the costs associated with undershooting or overshooting the target
      position with the initial impulse. With practice, a performer is able to reduce
      the trial-to-trial variability associated with goal-directed movement through
      more consistent movement planning processes and more rapid online control. Part
      of the optimisation process is related to the development of an internal model of
      performance against which early afferent feedback can be evaluated. This
      framework for examining speed, accuracy and energy expenditure in goal-directed
      reaching can be used to help understand the breakdown of efficient limb control
      due to fatigue, ageing and pathology.

PMID- 19401894
TI  - Manifestations of shoulder fatigue in prolonged activities involving low-force
      contractions.
AB  - Shoulder fatigue has been suggested to be a useful risk indicator for shoulder
      disorders in repetitive, low-force work tasks. In contrast to high-force or
      purely isometric tasks, it is unclear whether measurable fatigue develops in
      realistic low-force work. The question addressed in this review was: 'Is there
      evidence of objective signs of fatigue in the shoulder region in realistic, low
      force work tasks?' Studies on objective measures of fatigue applied in realistic
      low-force work tasks were systematically reviewed, using a task duration of more
      than 1 h and an intensity level of less than 20% maximum voluntary contraction
      (MVC) for the median trapezius activation level as inclusion criteria. Thirteen
      studies were found to fulfil the criteria. All these studies addressed fatigue
      related changes in the electromyographic signal in the descending part of the
      trapezius muscle. Seven did find a combination of frequency decrease and
      amplitude increase over time, which is generally considered as an objective
      manifestation of fatigue. Thus, there is evidence of objective signs of fatigue
      in some of the realistic, low-force tasks. The intensity level appeared to be a
      main determinant here. In the studies demonstrating signs of fatigue an intensity
      level of 15%MVC or more was used, while the intensity level in the studies with a
      negative result was generally lower.

PMID- 19401897
TI  - A single 10-min bout of cold-water immersion therapy after strenuous plyometric
      exercise has no beneficial effect on recovery from the symptoms of exercise
      induced muscle damage.
AB  - The purpose of this study was to examine the effectiveness of a single bout of
      cold-water immersion on recovery from exercise-induced muscle damage. Eighteen
      physically active female volunteers (age 19.9 (+/-0.97 years), height 1.66 (+/
      0.05 m), mass 63.7 (+/-10 kg), completed 10 sets of 10 counter-movement jumps to
      induce muscle damage and were randomly allocated to a control or treatment group.
      The treatment group was given a single 10-min bout of lower limb cold-water
      immersion therapy at 10 degrees C immediately following damage-inducing exercise.
      Indicators of muscle damage (plasma creatine kinase activity, perceived soreness
      and maximal voluntary contraction of the quadriceps) were assessed immediately
      prior to counter-movement jumps, and at 1, 24, 48, 72 and 96 h, following the
      damaging exercise. Significant (p = 0.05) time effects were recorded on all
      indicators of muscle damage, but there were no significant group or group x time
      interaction effects found on any of the measured variables. The results indicate
      that a single bout of cold-water immersion after a damaging bout of exercise has
      no beneficial effects on the recovery from exercise-induced muscle damage.

PMID- 19401896
TI  - Relationships between leisure-time energy expenditure and individual coping
      strategies for shift-work.
AB  - A total of 13 to 14% of European and North American workers are involved in shift
      work. The present aim is to explore the relationships between coping strategies
      adopted by shift workers and their leisure-time energy expenditure. Twenty-four
      female and 71 male shift workers (mean +/- SD age: 37 +/- 9 years) completed an
      adapted version of the Standard Shift-work Index (SSI), together with a leisure
      time physical activity questionnaire. Predictors of age, time spent in shift
      work, gender, marital status and the various shift-work coping indices were
      explored with step-wise multiple regression. Leisure-time energy expenditure over
      a 14-d period was entered as the outcome variable. Gender (beta = 7168.9 kJ/week,
      p = 0.023) and time spent in shift work (beta = 26.36 kJ/week, p = 0.051) were
      found to be predictors of energy expenditure, with the most experienced, male
      shift workers expending the most energy during leisure-time. Overall
      'disengagement' coping scores from the SSI were positively related to leisure
      time energy expenditure (beta = 956.27 kJ/week, p = 0.054). In males,
      disengagement of sleep problems (beta = -1078.1 kJ/week, p = 0.086) was found to
      be negatively correlated to energy expenditure, whereas disengagement of domestic
      related problems was found to be positively related to energy expenditure (beta =
      1961.92 kJ/week, p = 0.001). These relations were not found in female shift
      workers (p = 0.762). These data suggest that experienced male shift workers
      participate in the most leisure-time physical activity. These people 'disengage'
      more from their domestic-related problems, but less from their sleep-related
      problems. It is recommended that physical activity interventions for shift
      workers should be designed with careful consideration of individual domestic
      responsibilities and perceived disruption to sleep.

PMID- 19401898
TI  - Low-back problems in recreational self-contained underwater breathing apparatus
      divers: prevalence and specific risk factors.
AB  - Low-back problems (LBP) are one of the most common musculoskeletal disorders in
      the general population, with reported lifetime prevalences of 50% to 80%. Also,
      certain sports participants (e.g. gymnasts, alpine skiers, runners) are at risk
      of LBP and its repercussions. This epidemiological study was undertaken to
      examine the lifetime and 1-year prevalence of LBP among recreational Flemish self
      contained breathing apparatus (scuba) divers and to identify general and sport
      specific risk factors associated with the occurrence of LBP. A retrospective self
      assessment questionnaire was developed and assessed for validity and reliability,
      to gather data concerning demographics, LBP prevalence and associated risk
      factors and injuries among active scuba divers. A total of 181 recreational scuba
      divers (men: n = 138, mean age 40.3 +/- 12.8 years; women: n = 43, mean age 35.0
      +/- 10.9 years) from 10 randomly selected internationally recognised scuba diving
      clubs participated in the study. Lifetime and 1-year prevalence of LBP among
      recreational Flemish scuba divers were 55.8% and 50.3%, respectively. General
      risk factors for LBP were found to include prior history of LBP, structural
      abnormalities, heavy workload, pregnancy and parturition, general fatigue and
      bending forwards and backwards. Scuba divers suffering from LBP generally had a
      significantly higher dive certificate than those without LBP (p = 0.007).
      Symptomatic scuba divers also used significantly more weights on their weight
      belts during indoor training (p = 0.003) and during outdoor dives with a dry suit
      (p = 0.044) as compared to asymptomatic scuba divers. In scuba diving, reliable
      sport-specific risk factors for LBP were found to be scarce. Further
      biomechanical research is required to point out whether or not scuba diving
      characteristics actually contribute to LBP.

PMID- 19401899
TI  - Tracing the process of expertise in a simulated anticipation task.
AB  - Skilled perceptual-cognitive performance is assumed to require superior
      anticipation, yet few researchers have explored how individual differences in
      processing measures mediate superior performance, particularly when
      characteristics of the task are systematically changed from trial to trial. This
      study examined how advance cue information influences anticipation using a
      simulated cricket batting task. Skilled (n = 10) and less skilled (n = 10)
      batters moved in response to life-size video images of 36 deliveries by fast and
      spin bowlers. Skilled participants (mean 37.3, SD 2.8 mm) were significantly more
      accurate at anticipating ball position as it passed through the strike zone than
      less skilled batters (mean 48.9, SD 5.9 mm, p < 0.05). Skilled batters fixated on
      central areas of the body and searched more locations (p < 0.05). Batters used
      fixations of longer duration and focused more on the ball and hand when viewing
      spin compared to fast bowlers (both p < 0.05). Visual behaviour is constrained by
      the task parameters and participant skill level. An analysis of immediate
      retrospective reports and eye fixations indicated that skilled batters search and
      encode scenes at a richer and more sophisticated level than less skilled players.

PMID- 19401900
TI  - Effects of simulated firefighting on the responses of salivary cortisol, alpha
      amylase and psychological variables.
AB  - The aim of this study was to evaluate the effects of a simulated firefighting
      intervention on salivary alpha-amylase (sA-A), free cortisol (sC), anxiety
      (STAI), and profile of mood states (POMS) in 20 male firefighters (age 32 +/- 1
      years, VO(2peak): 43 +/- 5 ml/kg per min). During the 12-min firefighting
      intervention (ambient temperature: 13 +/- 1 degrees C; relative humidity: 63 +/-
      1%), individuals spent 63 +/- 28% of the time working at heart rate (HR) >85% of
      individual HR(max), [La] (peak) 9.2 +/- 2.9 mM and ratings of perceived exertion
      16 +/- 2. At 30 min post-intervention significant (p < 0.001) increases in sA-A
      (174%) and sC (109%) were found with regard to values recorded before and after
      90 min of the firefighting intervention. Since no differences emerged between pre
      intervention and post intervention for STAI and POMS values, the hormonal changes
      were attributable to the intense physical stress of the simulated intervention.
      Further research is needed during real firefighting activities, where high
      emotional stress may also be present.

PMID- 19401901
TI  - The effect of breast support on kinetics during overground running performance.
AB  - Changes in ground reaction forces that result from different breast support
      conditions may have implications for sports performance and transmission of
      forces through the skeleton. The aim of this investigation was to compare kinetic
      variables and breast motion in a no-bra, everyday-bra and two sports-bra
      conditions. Following ethical approval, eight female participants with D-cup
      breasts had retro-reflective markers placed on the left and right nipples,
      anterior superior iliac spines and clavicles. Five calibrated ProReflex infra-red
      cameras (100 Hz; Qualisys) measured 3-D displacement of markers and synchronised
      kinetic data were collected using a force platform (500 Hz, Kistler 9281CA). A
      repeated measures one-way ANOVA revealed a significantly higher medial impact
      force in the no-bra condition (0.15 times body weight) compared with the
      compression sports-bra condition (0.12 times body weight) (F = 3.64 (3,21), p =
      0.03). Findings suggest that inadequate breast support affects a female's running
      kinetics, which may have negative physiological consequences on sports
      performance.

PMID- 19401904
TI  - Low dose radiation-induced adaptive response preventing HPRT mutation is Fhit
      independent.
AB  - PURPOSE: To study whether fragile histidine triad (Fhit) prevents IR-induced
      hypoxanthineguanine phosphoribosyltransferase (HPRT) mutation and whether Fhit
      plays any role in preventing HPRT mutation through low dose-induced adaptive
      response. MATERIALS AND METHODS: Establishing human cell lines with or without
      Fhit expression by making constructs expressing hemagglutinin (HA) alone or HA
      Fhit fusion protein and transfecting the vector to HeLa cells. The effects of
      Fhit on ionising radiation (IR)-induced mutation were examined by observing HPRT
      mutation rates in the established cell lines following different doses of IR. The
      role of Fhit on low dose IR-induced adaptive response were examined by observing
      HPRT mutation rates in the established cell lines that were exposed to 0.1 Gy and
      followed with high dose IR or ultraviolet (UV) exposure. RESULTS: Low dose (0.1
      Gy) does not affect HPRT mutation rates in these cell lines. Fhit prevents high
      dose IR (> or = 2 Gy)-induced mutation as it prevents UV-induced mutation.
      However, low dose of IR (0.1 Gy)-induced adaptive response prevents both high
      doses of IR and UV-induced mutation in both the cells with and without Fhit
      expression. CONCLUSIONS: Fhit prevents IR-induced HPRT mutation and preventing
      mutation through low dose of IR-induced adaptive response is Fhit independent.

PMID- 19401903
TI  - Imaging of radiation effects on cellular 26S proteasome function in situ.
AB  - PURPOSE: The classical radiobiological paradigm is that DNA is the target for
      cell damage caused by ionising radiation. However, evidence is accumulating that
      other constituents, such as the membrane, organelles, and proteins, are also
      important targets. We have shown that the isolated 26S proteasome is one such
      target and here we wish to substantiate it within the cell, in situ. MATERIALS
      AND METHODS: We used confocal microscopy to quantitatively detect and
      subcellularly localise radiation-induced 26S proteasome inhibition in cells
      expressing an ornithine decarboxylase degron that targets a fused Zoanthus
      species green (ZsGreen) fluorescent protein reporter specifically to the 26S
      proteasome. RESULTS: Exposure of cells to a range of radiation doses, even as low
      as 0.05 Gy inhibited 26S activity within minutes. Initially, punctate nuclear
      ZsGreen fluorescence was observed that became cytoplasmic after seven hours -- a
      pattern distinct from the diffuse homogeneous fluorescence of cells incubated in
      the conventional proteasome inhibitor MG-132. CONCLUSIONS: Our study clearly
      indicates that the 26S proteasome is a radiation target with physiological
      consequences and introduces a new perspective in mechanistic investigations of
      cellular responses to stresses.

PMID- 19401905
TI  - Silk'n--a novel device using Home Pulsed Light for hair removal at home.
AB  - A small, light-weight, low-energy, and low-cost IPL system designed for home use
      (Silk'n; HomeSkinovations, Kfar, Saba, Israel) was tested for efficacy and safety
      on 34 test individuals and 92 sites. Each of the patients underwent informed
      consent and performed self-treatment at the clinic supervised by an experienced
      laser hair removal nurse. The pre- and post-treatment hair counts were performed
      and the reduction counts were analyzed by a blinded observer.

PMID- 19401907
TI  - Acquisition and analysis of 3D mandibular movement using a device based on
      electromagnetic sensors and a neural network.
AB  - In dental medicine, the study of mandibular movement has an important role in
      oral rehabilitation as it allows diagnosis of pathologies in the
      temporomandibular joint and the definition of adequate treatment plans. In this
      paper, a new device specially developed for the acquisition and analysis of 3D
      mandibular movement is presented. A facial arc is adopted as its main support
      structure and electromagnetic sensors are employed to acquire the mandibular
      movement. A neural network is used to transform the electrical signals output by
      the sensors into 3D Cartesian coordinates. A custom-made computer application is
      developed to display and analyse the movement acquired. The device is shown to be
      easy to use, comfortable for patients and capable of being produced at an
      affordable price.

PMID- 19401909
TI  - Work-related fatalities in the People's Republic of China.
AB  - Over the past several decades, work-related fatal incident reporting in China has
      become faster, more publicly accessible and, hence, a potentially more valuable
      process in support of the decision-making and enforcement actions of the
      government and safety professionals. A study was conducted to examine the
      characteristics of work-related fatalities in the People's Republic of China
      (PRC) available from the State Work Accident Briefing (SWAB) system. Injury
      incident records related to industries other than coal mining were downloaded
      from the SWAB system (April 2001 to March 2003). The findings were compared with
      a previously published regional work fatality study in China, data from the U.S.
      Census of Fatal Occupational Injuries, and estimates from the International Labor
      Organization (ILO). During the 2-year period, 1538 work-related events (7046
      worker fatalities) were recorded. Collisions (25.6%), drownings (14.6%), and
      structural collapses (12.5%) were the most frequently reported fatal events.
      Collisions (24.5%) and falls (14.5%) were the most frequent causes of cited fatal
      events. Transportation (105.87 per 100 000); mining industries other than coal
      mining and quarrying (73.28); and electricity, gas, and water supply (14.88) were
      the industries with the highest estimated fatality rates. Generally, regions with
      lower economic activity reported more fatalities. The fatal injury rate estimated
      from the SWAB system was 4.80 per 100,000 (U.S. rate 4.00). ILO estimates for
      1994 and 2002 were substantially higher than the estimates derived from the SWAB
      system. SWAB system differences with other data sources analyzed herein indicate
      that there remains room for system refinement.

PMID- 19401906
TI  - Ionising radiation and cancer risks: what have we learned from epidemiology?
AB  - PURPOSE: Epidemiologic studies of persons exposed to ionising radiation offer a
      wealth of information on cancer risks in humans. The Life Span Study cohort of
      Japanese A-bomb survivors, a large cohort that includes all ages and both sexes
      with a wide range of well-characterised doses, is the primary resource for
      estimating carcinogenic risks from low linear energy transfer external exposure.
      Extensive data on persons exposed for therapeutic or diagnostic medical reasons
      offer the opportunity to study fractionated exposure, risks at high therapeutic
      doses, and risks of site-specific cancers in non-Japanese populations. Studies of
      persons exposed for occupational and environmental reasons allow a direct
      evaluation of exposure at low doses and dose rates, and also provide information
      on different types of radiation such as radon and iodine-131. This article
      summarises the findings from these studies with emphasis on studies with well
      characterised doses. CONCLUSIONS: Epidemiologic studies provide the necessary
      data for quantifying cancer risks as a function of dose and for setting radiation
      protection standards. Leukaemia and most solid cancers have been linked with
      radiation. Most solid cancer data are reasonably well described by linear-dose
      response functions although there may be a downturn in risks at very high doses.
      Persons exposed early in life have especially high relative risks for many
      cancers, and radiation-related risk of solid cancers appears to persist
      throughout life.

PMID- 19401910
TI  - A modified oligostilbenoid, diptoindonesin C, from Shorea pinanga Scheff.
AB  - A new oligostilbenoid, diptoindonesin C, has been isolated from the tree bark of
      Shorea pinanga Scheff., along with the two known oligostilbenoids gnetin H and
      hopeaphenol, and a known coumarin scopoletin. The new oligostilbenoid was
      moderately active against brine shrimps Artemia salina.

PMID- 19401911
TI  - Hyoscyamal, a new tetrahydrofurano lignan from Hyoscyamus niger Linn.
AB  - In addition to the isolation and complete characterisation of a new lignan,
      hyoscyamal, three other compounds, balanophonin, pongamoside C and pongamoside D
      have been isolated from the seeds of Hyoscyamus niger. The structures of the
      compounds were settled on the basis of spectroscopic analysis. This is the first
      report on the isolation of these compounds from a solanaceous plant.

PMID- 19401912
TI  - Influence of growth phase on the essential oil composition of Ziziphora
      clinopodioides Lam.
AB  - Ziziphora clinopodioides belongs to the Lamiaceae family, that are widespread all
      over Iran. The leaves, flowers and stems of the plant are frequently used as wild
      vegetables or additives in food to offer aroma and flavour. The chemical
      composition of the essential oils obtained from the aerial parts of Z.
      clinopodioides Lam. in different growth stages were analysed by GC and GC-MS, and
      29 components were identified. Pulegone (30.1%), thymol (21.3%), p-mentha-3-en-8
      ol (12.9%) and piperitenone (9.3%) were the main components in the pre-flowering
      stage. In the flowering stage, pulegone (44.6%), p-mentha-3-en-8-ol (10.5%), 1,8
      cineoil (10.4%), piperitenone (8.7%) and thymol (6.7%) were identified as the
      main constituents and in the post-flowering stage, pulegone (41.3%), isomenthone
      (11.6%), p-mentha-3-en-8-ol (11%), p-mentha-3,8-diene (7.2%) and thymol (5.8%)
      were identified as the major components.

PMID- 19401913
TI  - Bromoanaindolone, a novel antimicrobial exometabolite from the cyanobacterium
      Anabaena constricta.
AB  - A new brominated indole alkaloid, designated as bromoanaindolone, was isolated
      from culture media of the cyanobacterium Anabaena constricta and was identified
      as 6-bromo-3-hydroxy-3-methyl-indol-2-one with a slight excess of the (3R)
      enantiomer. The molecular structure was elucidated on the basis of IR, MS and NMR
      data. This extracellular metabolite of A. constricta possessed antimicrobial
      (anticyanobacterial and antibacterial) activity in different test systems, such
      as suspension and porous matrix tests.

PMID- 19401914
TI  - A new oleanene triterpene from Gladiolus segetum Ker-Gawl.
AB  - A new pentacyclic oleanene triterpene, 2beta, 3beta, 16alpha, 28-tetrahydroxy
      olean-12-ene-23-oic acid (1), as well as the known pentacyclic triterpene
      medicagenic acid (2), have been isolated by different chromatographic techniques
      from the acid hydrolysate of the saponin fraction of Gladiolus segetum. The
      identification of these compounds was established by different methods of
      physical, chemical and spectral evidence.

PMID- 19401915
TI  - A new aromatic triterpene from Euonymus japonicus.
AB  - A new aromatic triterpene was isolated from the root bark EtOAc extract of
      Euonymus japonicus Thunb, and its chemical structure was elucidated mainly by
      analysis of MS and NMR spectra.

PMID- 19401916
TI  - Profiles of volatile compounds from nine new hybrids obtained by controlled
      crossings on olive Chemlali cultivar and Mediterranean varieties.
AB  - Virgin olive oil is a unique oil that can be consumed directly without any
      refining process. This particularity is due to the exceptional quality and
      flavour formed by the presence of more than 100 volatile compounds. Nine new
      hybrids obtained by controlled crossing of the Chemlali and seven ancient
      Mediterranean varieties cultivated in the same orchard under identical agronomic
      and pedoclimatic conditions were characterised by their main volatile compounds
      quantified by dynamic headspace-gas chromatography-MS. More than 40 volatile
      compounds from the main chemical groups, aldehydes, alcohols, ketones and esters,
      were identified by GC-MS and confirmed by their Linear Retention Index (LRI).
      Compounds produced from the lipoxygenase pathway were studied to determine the
      genetic potential and the influence on each crossing. Finally, Ward's method test
      and Pearson PCA analysis were used to check the ability of the volatiles to
      cluster the varietal virgin olive oils according to their genetics origin.

PMID- 19401917
TI  - Isolation of a minor nitro-alkaloid from the aerial parts of Duguetia furfuracea-
      Annonaceae.
AB  - The refractionation of an alkaloidal extract of the leaves and twigs of Duguetia
      furfuracea has provided a minor aporphinoid alkaloid, named (+)-8-nitrous
      isocorydine or (+)-1,2,3-trymethoxy-11-hydroxy-8-nitrous- aporphine. The
      structure of the new compound was elucidated by spectroscopic methods, notably 2D
      NMR and HRESIMS.

PMID- 19401918
TI  - Antiproliferative compounds of Helmiopsis sphaerocarpa from the Madagascar
      rainforest.
AB  - Bioassay-directed separation of an ethanol extract of the leaves of Helmiopsis
      sphaerocarpa L.C. Barnett (Sterculiaceae) led to the isolation of the new
      compound 14alpha,15alpha-epoxy-3beta-hydroxytaraxerane (1) and the four known
      compounds taraxerol (2), stigmast-5-en-3-ol (3), 5alpha,8alpha-epidioxy-24(S)
      methylcholesta-6,22-dien-3beta-ol (4), and 24xi-hydroperoxy-24-ethylcholesta
      4,28(29)-dien-3-one (5). The structure of the new compound 1 was established on
      the basis of interpretation of its 1D and 2D NMR spectroscopic data. All the
      compounds were tested against A2780 human ovarian cancer cell lines, and
      compounds 4 and 5 showed mild antiproliferative activity, with IC(50) values of
      16 and 7 microg mL(-1), respectively.

PMID- 19401919
TI  - Two novel butanol rhamnosides from an Indian traditional herb, Euphorbia hirta.
AB  - Two novel butanol rhamnopyranosides (1 and 2), along with nine known compounds (3
      11), have been isolated from various non-polar and polar extracts of an Indian
      traditional herb, Euphorbia hirta. The structures of the new compounds were
      elucidated as n-butyl-1-O-beta-L-rhamnopyranoside (1) and n-butyl-1-O-alpha-L
      rhamnopyranoside (2) by spectroscopic methods including IR, HR-FABMS, 1D and 2D
      NMR techniques.

PMID- 19401920
TI  - Dunaliine A, a new amino diketone from Desmos dunalii (Annonaceae).
AB  - Dunaliine A (1), a new amino diketone, has been isolated from the leaves of
      Desmos dunalii together with four known dihydrochalcones: 2',4-dihydroxy-4',6'
      dimethoxy-3',5'-dimethyldihydrochalcone (2), 2',4-dihydroxy-4',6'
      dimethoxydihydrochalcone (3), 2',4-dihydroxy-4',5',6'-trimethoxydihydrochalcone
      (4) and 2',4-dihydroxy-5'-methyl-4',6'-dimethoxydihydrochalcone (5). The
      structures of these compounds were established notably by spectral analysis (1D-
      and 2D- (1)H, (13)C NMR), UV, IR and HRMS.

PMID- 19401921
TI  - Anti-cancer effect of two alkaloids: 2R and 2S-bgugaine on mastocytoma P815 and
      carcinoma Hep.
AB  - The 2-alkylpyrrolidine R-bgugaine, a natural alkaloid isolated from tubers of
      Arisarum vulgare Targ. Tozz. (Araceae), and its isomer S-bgugaine, obtained by an
      asymmetric synthesis, were examined for their cytotoxic activities on two
      cancerous cellular lines: the murine mastocytoma cell line P815 and the human
      laryngeal carcinoma cell line Hep. These two alkaloids exhibited an important
      cytotoxic activity on these two cancerous cellular lines. The concentrations
      required to induce 50% of lysis (IC(50)) for R-bgugaine and S-bgugaine alkaloids
      were determined, and are 10 and 5 microg mL(-1), and 5 and 100 microg mL(-1),
      respectively, for the mastocytoma P815 and carcinoma Hep, compared with those of
      Adriamycine (5 microg mL(-1) for P815 cell line and 5 microg mL(-1) for Hep cell
      line), taken as positive controls.

PMID- 19401922
TI  - A p-quinol isoflavan and two new isoflavanones from Desmodium canum.
AB  - Three further minor isoflavonoid components (1-3) of the dichloromethane extract
      of Desmodium canum root have been isolated: two of them are complex isoflavanones
      with structures 1 and 2 biogenetically related to the previously isolated
      compounds 1a and 2a. The third is a complex isoflavan where the isoprenyl
      substituent and the aromatic A-ring yielded a p-quinol nucleus.

PMID- 19401924
TI  - Structure analysis of an acidic polysaccharide isolated from green tea.
AB  - An acidic polysaccharide (ATPS-2) was isolated and purified from coarse green
      tea. ATPS-2 with peak molecular weight of 4430 Da was composed of rhamnose,
      arabinose, galactose and galacturonic acid. Structure features of the purified
      ATPS-2 were investigated by a combination of chemical and instrumental analysis,
      such as periodate oxidation, Smith degradation, (1)H NMR, (13)C NMR, COSY, HSQC,
      HMBC and ROESY spectrum. It was found that ATPS-2 was a pectic polysaccharide.
      The backbone proved to consist of the smooth region of alpha-1,4-D
      galactopyranosyluronan blocks interconnected by 1,2-linked rhamnose residues
      involved in the linear sugar chain. The ramified hairy regions were shown to
      contain the following of the backbone: -->4)-alpha-D-GalpA-(1 --> 2)-alpha-L-Rhap
      (1 --> 4)alpha-D-GalpA-(1--> and the side chains attached to the residues of
      rhamnopyranose of these fragments. The backbone galacturonic acid residues of
      ATPS-2 were partially O-methyl esterified and acetylated. The side chains contain
      linear and branched alpha-L-Araf and beta-D-Galp residues.

PMID- 19401923
TI  - Flowerhead volatile oil composition of soilless culture-grown Chrysanthemum
      balsamita L.
AB  - Hydrodistilled flowerhead volatile oil composition of soilless culture-grown
      Chrysanthemum balsamita L. was studied for its components by GC/MS. Thirty-one
      constituents were quantified, comprising 94.08% of the oil. Oxygenated
      monoterpenes (78%) and sesquiterpenes (sesquiterpene hydrocarbons and oxygenated
      sesquiterpenes) (14.88%) were the major classes of identified components
      occurring in higher proportions. The predominant constituents of the volatile oil
      were carvone (52.01%), alpha-thujone (11.04%), (E)-beta-farnesene (3.91%),
      limonene (2.7%) and delta-cadinol (2.18%). Five sesquiterpenoidal components,
      namely gamma-gurjunene (1.74%), (Z, E)-farnesol (1.16%), delta-cadinene (1.14%),
      alpha-cedrene (1.11%) and beta-copaene-4-alpha-ol (0.44%) were identified for the
      first time from the volatile oil of costmary. Considering volatile oil
      components, the chemical profile of flowerhead volatile oil of soilless culture
      grown C. balsamita L. was comparable with previously reported wild- and field-
      grown plants of C. balsamita L.

PMID- 19401925
TI  - Intensity of therapy services: what are the considerations?
AB  - Research on intensity of therapy services is limited and perspectives often vary
      considerably among families, therapists, administrators, policy makers, and
      health insurers. In this commentary, the authors share their perspectives on
      intensity of physical therapy and/or occupational therapy services for children
      with developmental conditions. Five considerations are discussed: episode of
      therapy, readiness for activity and participation, method of service delivery,
      the distinction between intensity of therapy and practice of activity in natural
      environments, and the link between skill level and method of service delivery. We
      conclude that for children with developmental considerations, method of service
      delivery and intensity of therapy may differ for each episode of therapy based on
      contextual factors including child and family priorities and goals. In most
      situations, more than one method of service delivery can and should occur
      simultaneously.

PMID- 19401926
TI  - Measuring outcomes of family-centered intervention: development of the Life
      Participation for Parents (LPP).
AB  - Raising a child with disabilities impacts the ability of parents to participate
      in life situations. This paper describes the development of a new instrument,
      Life Participation for Parents, to measure outcomes of pediatric therapy on
      parental participation. Items were reviewed by six occupational therapists with
      experience in pediatrics and instrument development. The number of items was
      reduced to 23. The resultant instrument was completed by 29 parents of children
      with disabilities. Their scores were reviewed by the nine occupational therapists
      working with the children. Parent and therapist respondents were interviewed
      regarding item content. Instrument responses were evaluated for internal
      consistency. The respondents confirmed the face and content validity of the
      construct, variability in responses, and readability of the items. Good internal
      consistency for items was demonstrated (Cronbach's alpha .85). The preliminary
      results indicate that the Life Participation for Parents is a promising tool for
      evaluating parental issues and measuring parent outcomes in family-centered
      practice.

PMID- 19401928
TI  - Mobility experiences of adolescents with cerebral palsy.
AB  - The purpose of this study was to describe how youth with cerebral palsy
      experience mobility in their daily lives using a phenomenological approach. The
      participants were 10 youth with cerebral palsy, 17 to 20 years of age, selected
      using purposeful sampling with maximum variation strategies. A total of 14
      interviews were completed. Transcripts were analyzed for key concepts and themes.
      Credibility was established through triangulation of researchers and member
      checking. Participants viewed mobility as important for self-sufficiency. Youth
      who walked and also used wheeled mobility spoke of making choices. Safety and
      efficiency were important considerations when making choices. Some participants
      had mobility preferences at home that may not be safe, practical, or socially
      appropriate at school or in the community. Youth spoke of constantly adapting to
      situations that often reflected a lack of control over the environment. Youth
      indicated the need for constantly planning ahead to go places and do things. Most
      participants were dependent on others for transportation and expressed
      dissatisfaction with public transportation. Safe and efficient mobility to enable
      participation in daily activities appears to be the primary concern of youth with
      cerebral palsy.

PMID- 19401927
TI  - Within a family-centered practice, how can family outcomes be identified?

PMID- 19401929
TI  - Analysis of physical therapy goals in a school-based setting: a pilot study.
AB  - The purpose of this pilot study was to analyze physical therapy goals for
      students receiving services in the school setting and to determine if these goals
      are measurable and context specific. The Individualized Education Program (IEP)
      of 32 students receiving physical therapy services was analyzed to determine the
      type of task and context that were specified, and the type of measurement
      criteria used. Goals were categorized using a Goal Analysis Form developed for
      the study. Generally, goals were centered on task performance; however, most
      goals (72%) were not context specific, and few goals (6%) addressed academic
      tasks. The majority of goals (84%) utilized measurement criteria; the most
      commonly used criterion was level of independence (49%). The Goal Analysis Form
      is a tool that can be used to analyze the extent to which IEP goals are context
      specific and measurable. Therapists in school settings are expected to formulate
      goals that are measurable and context specific.

PMID- 19401930
TI  - Comparison of cursive handwriting instruction programs among students without
      identified problems.
AB  - The purpose of this study was to compare the effects of cursive handwriting
      programs in improving letter legibility and form in third-grade students without
      identified handwriting problems. Four months into the school year, cursive
      handwriting was assessed for a sample of convenience of 50 third-grade students.
      Subsequently, students received instruction for 10-15 minutes daily for 6 weeks
      using either Handwriting without Tears, Loops and Other Groups programs, or, as a
      control condition, continued instruction in the Zaner-Bloser program. Student
      handwriting for all programs improved from pretest to posttest. Posttest
      comparisons indicated no significant differences between programs. The results
      suggest that the method of handwriting instruction has a limited short-term
      impact on cursive letter legibility and form for children without handwriting
      problems.

PMID- 19401931
TI  - Psychometric properties of the revised Developmental Coordination Disorder
      Questionnaire.
AB  - The Developmental Coordination Disorder Questionnaire (DCDQ) is a parent
      completed measure designed to identify subtle motor problems in children of 8 to
      14.6 years of age. The purpose of this study was to extend the lower age range to
      children aged 5 to 7 years, revise items to ensure clarity, develop new scoring,
      and evaluate validity of the revised questionnaire. Additional items with
      improved wording were generated by an expert panel. Analyses of internal
      consistency, factor loading, and qualitative/quantitative feedback from
      researchers, clinicians, and parents were used to select 15 items with the
      strongest psychometric properties. Internal consistency was high (alpha = .94).
      The expanded questionnaire was completed by the parents of 287 children, aged 5
      15 years, who were typically developing. Logistic regression modeling was used to
      generate separate cutoff scores for three age groups (overall sensitivity = 85%,
      specificity = 71%). The revised DCDQ was then compared to other standardized
      measures in a sample of 232 children referred for therapy services. Differences
      in scores between children with and without DCD (p < .001) provide evidence of
      construct validity. Correlations between DCDQ scores and Movement Assessment
      Battery for Children (r = .55) and Test of Visual-Motor Integration (r = .42)
      scores support concurrent validity. The results provide evidence that the revised
      DCDQ is a valid clinical screening tool for DCD.

PMID- 19401932
TI  - Results of the Sensory Profile in children with suspected childhood apraxia of
      speech.
AB  - Speech-sound disorders are common in preschool-age children, and are
      characterized by difficulty in the planning and production of speech sounds and
      their combination into words and sentences. The objective of this study was to
      review and compare the results of the Sensory Profile (Dunn, 1999) in children
      with a specific type of speech-sound disorder, childhood apraxia of speech (CAS),
      and to explore the relationship between sensory processing and sound-production
      deficits. Participants were identified prospectively through an interdisciplinary
      apraxia clinic at a tertiary care pediatric hospital, and results of the Sensory
      Profile were compiled and reviewed. Thirty-eight children aged 3 to 10 years with
      suspected CAS were evaluated from July 2003 to July 2005. The results of the
      Sensory Profile indicated a difference for these children in several factor
      clusters when compared to typical peers from the normative population of the
      Sensory Profile. These findings imply that children with suspected CAS may
      present with differences in sensory processing in addition to speech impairment.
      When present, these differences in sensory processing could be addressed with
      specific therapeutic approaches through occupational therapy or consultation with
      an occupational therapist.

PMID- 19401933
TI  - Clinical aspects of acute intermittent porphyria in northern Sweden: a population
      based study.
AB  - The objective of this study was to update the clinical issues of acute
      intermittent porphyria (AIP), as they have not been in focus for years, and to be
      aware of potentially associated disorders and social consequences. A total of 356
      gene carriers of AIP from northern Sweden participated in this retrospective
      population-based study. Eight mutations were found with a predominance of W198X
      (89%). Clinical manifestations of AIP (manifest AIP) were identified in 42%, 65%
      were women. Women were more severely stricken by AIP attacks concerning number
      and duration, hospital admission and early onset. Men reporting most attacks were
      > 40 years of age. In addition to traditional symptoms during attacks, fatigue
      was commonly described. Chronic AIP symptoms and disability pension due to AIP
      were reported in about 20% of subjects. Precipitating factors were reported with
      evident sex differences. Half of the gene carriers who were on medications used
      drugs considered not safe (in 1999), mainly antihypertensive drugs. Smoking was
      associated with high AIP attack frequency. Elevated levels of ALT, bile acids,
      creatinine, U-ALA and U-PBG and decreased levels of creatinine clearance were
      associated with manifest AIP. The same was true for hypertension and myalgia in
      the legs. Hepatoma was strikingly overrepresented. The high prevalence of
      manifest AIP in this study could be explained by a mutation-dependent penetrance.
      Our results emphasize the importance of early diagnosis, counselling and
      treatment of attacks, screening and treatment of associated disorders.

PMID- 19401934
TI  - Bacterial tracheitis: a multi-centre perspective.
AB  - The published literature on bacterial tracheitis is limited. We report the first
      multi-centre study of bacterial tracheitis together with a concise review of the
      literature. We conducted a retrospective study of cases admitted during the
      period 1993-2007 to 3 tertiary paediatric centres in the United Kingdom and 1 in
      Australia. A total of 34 cases were identified. 31 patients (91%) required
      intubation. Complications included cardiorespiratory arrest in 1, ARDS in 1,
      hypotension in 10, toxic shock syndrome in 1 and renal failure in 1 patient(s).
      Staphylococcus aureus was the most commonly implicated bacterial organism,
      isolated from the respiratory tract in 55.8% of the cases overall. Other
      pathogens commonly isolated from the respiratory tract included Streptococcus
      pyogenes (5.9%), Streptococcus pneumoniae (11.8%) and Haemophilus influenzae
      (11.8%). Viral coinfection was identified in 9 (31%) of the 29 cases in whom
      immunofluorescence testing was performed (influenza A in 4 cases; parainfluenza 1
      in 2 cases; parainfluenza 3 in 2 cases; adenovirus in 1 case). The combined
      experience from 4 major paediatric intensive care units suggests that bacterial
      tracheitis remains a rare condition with an estimated incidence of approximately
      0.1/100,000 children per year. Short-term complications were common but long-term
      sequelae were rare. There were no fatal outcomes, which contrasts with the high
      historical mortality rates and likely reflects improvements in intensive care
      management.

PMID- 19401935
TI  - Comparison of two methods of controlled mobilisation of repaired flexor tendons
      in zone 2.
AB  - The results after primary repair of zone 2 flexor tendon injuries were evaluated
      in 263 fingers in 192 patients using two different early-controlled mobilisation
      programmes. There were 126 men and 66 women (age range 18 to 57 years) divided
      into two groups. Ninety-eight patients with 137 fingers were treated by early
      active mobilisation with dynamic splinting method according to a modified
      Kleinert regimen (Washington regimen), and 94 patients with 126 fingers were
      managed with a controlled passive movement regimen postoperatively. During this
      evaluation patients were evaluated for total active movement (TAM), grip
      strength, and disabilities of arm, shoulder, and hand (DASH) questionnaire. All
      patients were also reviewed 12 weeks after operation and the results assessed by
      the Buck-Gramcko-II system. Total active movement was "excellent" in the
      Washington regimen group (n=119, 87%), while excellent results of the fingers
      were achieved in the controlled passive movement group (n=94, 75%). The mean grip
      strength of the injured hand was 89% that of the non-injured side in the
      Washington regimen group, compared with 81% in the controlled passive movement
      group. The mean DASH score was 30 and 42 in the two groups, respectively. We
      think that controlled active mobilisation with dynamic splinting improves the
      outcome in the upper extremity, including range of movement, grip strength, and
      functional state of the hand in repairs of the flexor tendons.

PMID- 19401936
TI  - Wavy line closure for revision of abdominal scars with suture marks in children.
AB  - Although various methods are available to treat scars, it is difficult to manage
      those with suture marks that look like fish-bones, mainly because a large amount
      of tissue between the suture marks must be discarded with the scar. We report the
      wavy line closure for revision of abdominal scars with suture marks in three
      children who were operated on for congenital abdominal diseases. The entire scar,
      including all the suture marks, was excised using an incision consisting of a
      pair of smoothly waved lines. This incision makes it possible to reduce the
      tension on the wound by preserving the normal skin between the suture marks,
      which is followed by fine scars. The resulting wave-shaped scar is less
      noticeable and more resistant to postoperative contracture than a straight scar.

PMID- 19401937
TI  - Flexion contracture of the fingers caused by sarcoidosis: an 11-year follow-up.
AB  - We report the long-term result of operative treatment of a flexion contracture of
      the fingers resulting from sarcoidosis, in which the contracture recurred. Even
      with complete excision of the granulomatous lesion, a new lesion may appear in a
      previously healthy area, so a radical cure by operation alone is difficult.

PMID- 19401939
TI  - Magnetic resonance imaging of peripheral nerve tumours in the upper extremity.
AB  - Clinical assessment and various diagnostic tools, particularly magnetic resonance
      imaging (MRI), of tumours of peripheral nerves are used to get an accurate
      diagnosis and to plan surgical intervention. Our purpose was to examine the
      usefulness of MRI in assessing nerve tumours in the upper extremity. Medical
      records of 19 patients (20 MRI examinations) with 29 histopathologically verified
      benign nerve tumours were examined retrospectively. In 12/20 cases MRI suggested
      a correct diagnosis of the type of nerve tumour. An additional 3/20 cases had an
      uncertain diagnosis, but nerve relations to the tumour were established. In 5/20
      cases MRI gave a doubtful diagnosis with no suspicion of the tumour being located
      in a nerve trunk. MRI can localise and diagnose a nerve tumour in the upper
      extremity in 75% of cases, but it is difficult to specify the type of tumour.

PMID- 19401938
TI  - The Arrhinias.
AB  - The Arrhinias consist of three groups of malformations: the Total Arrhinias (T
      AR), the Hemi-Arrhinias (H-AR, often called Hemi-Nasal Ageneses) and the
      Proboscis Lateralis (P.L.) This work deals with 51 cases of Arrhinias gathered
      within 35 years (8 T-AR, 25 H-AR, and 18 P.L): their anatomy, clinical signs, and
      some indications for treatment; but it does not extend to a discussion for their
      etiopathology. However, the T-AR and the H-AR represent ageneses, whereas the P.L
      represents a dysgenesis. The anomalies common to the three groups of Arrhinias
      are many: the agenesis of the nasal bones, the telecanthus which is often in
      contrast to the hypo-telorbitism, the obstruction of the naso-lacrimal passage,
      the ectasia of the lacrimal sac with an erosion of the inferomedial angle of the
      orbit, the hypopneumatization of the maxillary sinus and a small maxilla, the
      unerrupted canines, the flattened fronto-nasal process, the obliteration of the
      cribriform plate, the dysplasia in the root of the eyebrows, the transverse
      hypoplasia of the upper lip, the frequency of microphthalmia, colobomas of the
      iris and nystagmus. Cleft lip and palate are frequently associated with the
      Arrhinias (see Table I) and also other facial malformations, but in different
      proportions, according to groups. They are: cryptophtalmias, eyelid coloboma,
      fronto-orbital encephalocele, agenesis of the premaxilla or prolabium, microtia.
      (See Table II) The basic principles of the treatment are the following: In the T
      AR, a nasal passage should initially be bored through the maxilla, or there
      should be a displacement of the two halves of the mid-face by a procedure known
      as "facial bipartition". This nasal passage should be epithelialized and
      maintained wide open to the pharynx until the nasal construction. In the H-AR, it
      is sufficient to create an epithelialized passage through the curtain of bone
      where one would expect the pyriform rim to be and carry this passage through the
      septum into the contralateral nasal airway. Then, regardless of the type of
      arrhinia, the nasal construction is carried out with a forehead flap and bone
      grafts. The first grafts are either iliac or tibial, and subsequent ones are
      generally outer table calvarial grafts harvested from the parietal region. Later,
      there are further procedures: a maxillary advancement, a lengthening of the
      central midface, the final stages of the nasal construction, the elevation of the
      medial canthus, and the restoration of the infero-medial angle of the orbit (but
      rarely an efficient lacrimal drainage). The earliest stage for surgery can be
      debated. A strategy for treatment is suggested. Finally, 20 brief comments are
      made, which are as much questions asked concerning the three groups of arrhinia
      and their relationship with other centro-facial and latero-facial malformations.

PMID- 19401940
TI  - Experience of sclerotherapy and embolosclerotherapy using ethanolamine oleate for
      vascular malformations of the head and neck.
AB  - Sclerotherapy is effective in the treatment of vascular malformations. However,
      in lesions with relatively high blood flow, its effect is not always adequate. We
      therefore developed a three-grade classification of vascular malformations to
      facilitate the selection of treatments according to vascular flow. We also
      developed the technique of embolosclerotherapy, in which transarterial
      embolisation is done before sclerotherapy to control blood flow in the lesion
      during sclerotherapy. We now have 14 years' experience with 112 cases of vascular
      malformations of the head and neck treated with sclerotherapy. Results were
      evaluated with pretreatment and post-treatment photographs, and reduction of
      volume was calculated on findings from magnetic resonance imaging. Clinical
      improvement in 110 cases was graded as excellent in 32 (29%), good in 48 (43%),
      fair in 19 (17%), and poor in 11 (10%). In 84 cases, mean rate of reduction of
      volume was 35%. The most common complication was haemolytic haemoglobinuria
      (n=37, 33%). Our results suggest that this three-grade classification is useful
      to judge resistance to sclerotherapy and decide on treatment. Our experience
      indicates that ethanolamine oleate (EO), with or without arterial embolisation,
      was effective using our classification of vascular dynamics. We consider EO to be
      equivalent or superior to other sclerosants such as ethanol.

PMID- 19401941
TI  - Bilateral acute carpal tunnel syndrome after combined pancreatic and renal
      transplant.
AB  - We present an unusual case of immediate bilateral acute carpal tunnel syndrome
      that followed combined pancreatic and renal transplantation and responded to
      decompression after failed conservative treatment.

PMID- 19401942
TI  - Advantages of open treatment for syndactyly of the foot: defining its
      indications.
AB  - For the repair of syndactyly of the foot, skin grafting is often used to close
      the skin defect, but open treatment is not common. However, with grafting, an
      additional scar at the donor site and patchwork-like scar at the recipient site
      are inevitable. Our aim was to describe the process of epithelialisation and
      define the indications for open treatment of syndactyly of the foot. The open
      treatment was used on 16 webs. The texture of epithelialised surface resembled
      volar skin; the visible scar was mainly at the dorsal edge; and web creep
      occurred predominantly on the volar side and resembled the natural slope of the
      commissure. Open treatment is better than skin grafting because of better match
      of texture without a patchwork-like scar, and it is indicated in cases of simple
      incomplete syndactyly of the foot that extends proximal to the distal
      interphalangeal joint.

PMID- 19401943
TI  - Blastomycotic hand infections.
AB  - We report two cases of disseminated blastomycotic infections with involvement of
      the hand occurring in the absence of identifiable risk factors.

PMID- 19401944
TI  - V-Y fasciocutaneous flap of the medial thigh including the long saphenous vein
      for reconstruction of intrapelvic dead space.
AB  - Some patients develop an intrapelvic infection and fistula caused by the presence
      of intrapelvic dead space after the resection of rectal cancer, and the treatment
      is sometimes quite difficult. We have developed a new surgical technique for the
      treatment and prevention of such fistulas that uses a fasciocutaneous flap from
      the medial thigh. A V-shaped fasciocutaneous flap with a pedicle on the anterior
      side of the thigh is designed on the medial thigh and gluteal region. After
      raising the fasciocutaneous flap that contains the long saphenous vein, the
      gluteal section including a thick layer of fatty tissue is de-epithelialised, and
      the flap is rotated and advanced towards the dead space to fill it. Four patients
      were operated on using our technique. One was a secondary reconstruction: the
      patient had developed a small fistula after reconstructive surgery, but it healed
      with conservative treatment. As a result, all four patients achieved satisfactory
      outcomes. The advantages of our technique include: no change in the position of
      the body is required for reconstruction; operations are simple; sufficient volume
      of tissue is obtained from the thick fatty tissues of the gluteal region; and the
      fasciocutaneous flap contains the long saphenous vein and has good venous
      circulation. We consider this technique useful for the reconstruction of
      intrapelvic dead space.

PMID- 19401945
TI  - Periosteal expansion of rabbit mandible with an osmotic self-inflatable expander.
AB  - We aimed to evaluate a new technique for intraoral expansion of soft tissue with
      a self-inflatable expander in rabbits. We placed a self-inflatable soft tissue
      expander bilaterally in eight rabbits under the periosteum of the mandible
      through an extraoral approach. The expander was left to self-inflate for two
      weeks, after which the animals were killed and specimens collected for
      histological examination. The self-inflatable soft tissue expanders expanded the
      periosteum. There were no dehiscences or infections. Histological observations
      showed no signs of any inflammatory reaction and there was no evidence of bony
      resorption. New bone had formed at the edges of the expanded periosteum. In the
      control area no new bone had formed. The osmotic soft tissue expander model for
      intraoral soft tissue and periosteal expansion suggests a promising way of
      creating a surplus of soft tissue that can be used to cover bone grafts.

PMID- 19401946
TI  - Lower rates of comorbidities in euthymic bipolar patients.
AB  - OBJECTIVE: This study assessed the frequency of axis I psychiatric comorbidities
      in euthymic bipolar patients and the clinical differences between patients with
      and without comorbidities. METHOD: In this study, 62 euthymic bipolar outpatients
      assessed using a clinical questionnaire underwent a structured diagnostic
      interview (SCID/CV-DSM-IV) as well as a symptoms evaluation (YMRS and HAM-D-17).
      RESULTS: The lifetime frequency of patients with comorbidities was 27.4%. The
      most frequent comorbidities were anxiety disorders (33.7%), and the positive
      associated variables were more advanced age, the presence of a steady partner, a
      first episode of the depressive type and lifetime attempted suicide. CONCLUSIONS:
      The lower frequency of comorbidities found in our study in comparison with those
      described in the literature may be due to the evaluation restricted only to
      euthymic patients. This suggests the importance of assessing psychiatric
      comorbidity in bipolar individuals while not in acute phases of the disorder.

PMID- 19401947
TI  - Co-morbidity of bipolar disorder in children and adolescents with attention
      deficit/hyperactivity disorder (ADHD) in an outpatient Turkish sample.
AB  - This study aimed to assess the prevalence of bipolar disorder (BPD) in children
      and adolescents with attention deficit hyperactivity disorder (ADHD), and to
      compare the clinical characteristics of a group with ADHD with a group with co
      morbidity of ADHD and BPD. The study includes 121 individuals, aged 6-16 years,
      with a diagnosis of ADHD. Co-morbidity of BPD was evaluated using the Schedule
      for Affective Disorders and Schizophrenia for School-age Children-Present and
      Lifetime version (K-SADS-PL) and the Parent-Young Mania Rating Scale (P-YMRS).
      The Child Behavior Checklist (CBCL) was used to assess psychopathology in two
      groups. Ten children (8.3%) in the ADHD sample received the additional diagnosis
      of BPD. The ADHD + BPD group had significantly higher scores than the ADHD group
      on withdrawn, anxiety/depression, social problems, thought problems, attention
      problems, aggression, externalization, total score items of CBCL, and on the P
      YMRS. It could be concluded that BPD is not a rare co-morbid condition in
      children with diagnosis of ADHD and subjects with this co-morbidity show more
      severe psychopathology than subjects with pure ADHD. Differential diagnosis of
      BPD disorder in subjects with ADHD seems crucial in establishing an effective
      treatment program, and therefore improving mental health outcomes.

PMID- 19401948
TI  - Endurance athletes: what is the optimal training strategy?

PMID- 19401949
TI  - Manipulation of rest period length induces different causes of fatigue in
      vertical jumping.
AB  - The aim of this study was to directly compare the causes of fatigue after a short
      and a long-rest interval between consecutive stretch-shortening cycle exercises.
      Eleven healthy males jumped with different resting period lengths (short=6.1+/-1
      s, long=8.6+/-0.9 s), performing countermovement jumps at 95% of their maximal
      jump height until they were unable to sustain the target height. After short- and
      long-rest, the maximal voluntary isometric contraction knee extension torque
      decreased (-7%; p=0.04), comparing to values obtained before exercise protocols.
      No change was seen from pre- to post-exercise, for either short- or long-rest, in
      biceps femoris coactivation (-1%; p=0.95), peak-to-peak amplitude (1%; p=0.95)
      and duration (-8%; p=0.92) of the compound muscle action potential of the vastus
      lateralis. Evoked peak twitch torque reduced after both exercise protocols
      (short=-26%, long=-32%; p=0.003) indicating peripheral fatigue. However, central
      fatigue occurred only after short-rest evidenced by a reduction in voluntary
      activation of the quadriceps muscle (-14%; p=0.013) measured using the
      interpolated twitch technique. In conclusion, after stretch-shortening cycle
      exercise using short rest period length, the cause of fatigue was central and
      peripheral, while after using long rest period length, the cause of fatigue was
      peripheral.

PMID- 19401951
TI  - Estrogens and the brain. Preface.

PMID- 19401953
TI  - Estrogens, brain, and behavior: lessons from knockout mouse models.
AB  - The use of animal models to effectively replicate problems such as hormone
      deficiencies, neurologic diseases, and brain injury and stroke has certainly made
      a vast contribution to understanding the neuroprotective effects of estrogen in
      the brain. Studies using gonadectomy procedures followed by 17beta-estradiol
      replacement have effectively demonstrated the positive effects that estrogen
      provides in cognitive performance and memory performance tasks. A major problem
      with such studies is that local brain aromatase (the estrogen-synthesizing
      enzyme) may still convert locally produced androgens to estrogens. Hence, such
      "estrogen-deficient" models may not be completely void of estrogen. The
      generation of the aromatase knockout (ArKO) and estrogen receptor knockout (ERKO)
      mouse models has enabled researchers to characterize the effects of complete
      estrogen deficiency within the brain and hence behavior. This review aims to
      compare and contrast the results of these various mouse models.

PMID- 19401952
TI  - Brain aromatization: classic roles and new perspectives.
AB  - Aromatization of testosterone to estradiol by neural tissue has classically been
      associated with the regulation of sexual differentiation, gonadotropin secretion,
      and copulatory behavior. However, new data indicate that the capacity for
      aromatization is not restricted to the endocrine brain and demonstrate roles for
      locally formed estrogens in neurogenesis and in responses of brain tissue to
      injury. This article summaries our current understanding of the distribution and
      regulation of aromatase in the brain and describes the classic and novel roles it
      plays. A better understanding of brain aromatization could shed new light on its
      physiologic and pathologic functions and someday lead to new, centrally acting
      drug therapies.

PMID- 19401955
TI  - Estradiol is a potent protective, restorative, and trophic factor after brain
      injury.
AB  - Estrogens are a group of pleiotropic steroid hormones that exhibit diverse
      mechanisms of action in multiple physiologic systems. Over the past 30 years,
      biomedical science has begun to appreciate that endogenous estrogens and their
      receptors display important roles beyond the reproductive system. Our growing
      appreciation of novel, nonreproductive functions for estrogens has fundamentally
      contributed to our knowledge of their role in human health and disease. Recent
      findings from the Women's Health Initiative have caused clinicians and scientists
      to question whether estrogens are protective factors or risk factors. In light of
      the dichotomy between basic science and clinical studies, this review will
      attempt to reconcile differences between them. We will focus on studies from our
      laboratory and others highlighting the beneficial properties of the most abundant
      endogenous estrogen, 17beta-estradiol, using in vivo and in vitro models of
      cerebral ischemia and neuronal injury. These studies demonstrate that 17beta
      estradiol powerfully protects the brain using multiple molecular mechanisms that
      promote: (1) decreased cell death, (2) increased neurogenesis, (3) an enhancement
      of neurotrophic support, and (4) the suppression of proinflammatory pathways.

PMID- 19401954
TI  - Sex, sex steroids, and brain injury.
AB  - Biologic sex and sex steroids are important factors in clinical and experimental
      stroke and traumatic brain injury (TBI). Laboratory data strongly show that
      progesterone treatment after TBI reduces edema, improves outcomes, and restores
      blood-brain barrier function. Clinical studies to date agree with these data, and
      there are ongoing human trials for progesterone treatment after TBI. Estrogen has
      accumulated an impressive reputation as a neuroprotectant when evaluated at
      physiologically relevant doses in laboratory studies of stroke, but translation
      to patients remains to be shown. The role of androgens in male stroke or TBI is
      understudied and important to pursue given the epidemiology of stroke and trauma
      in men. To date, male sex steroids remain largely evaluated at the bench rather
      than the bedside. This review evaluates key evidence and highlights the
      importance of the platform on which brain injury occurs (i.e., genetic sex and
      hormonal modulators).

PMID- 19401956
TI  - Mechanisms of action of estrogen in the brain: insights from human neuroimaging
      and psychopharmacologic studies.
AB  - Use of estrogen therapy in the perimenopausal and postmenopausal periods has been
      shown in several clinical trials to help women maintain a premenopausal level of
      cognitive function. What is not yet fully understood is how the neurobiological
      effects of estrogen contribute to these cognitive effects. This review explores
      data from two related bodies of human literature that provide compelling evidence
      in support of the biological plausibility that estrogen treatment can benefit
      cognition. The first half of the literature review focuses on studies from the
      estrogen neuroimaging literature, and the second half focuses on pharmacologic
      challenge studies assessing estrogen-neurotransmitter interactions. We integrate
      these two bodies of literature by focusing on the neurophysiologic underpinnings
      of estrogen effects on cognition and linking these clinical studies to
      preclinical studies. The focus on verbal memory is important because it is a
      cognitive function that has been shown to change with estrogen treatment and
      predict Alzheimer's disease risk but is not addressed by preclinical studies.
      Overall, we conclude that estrogen interacts with cholinergic and serotonergic
      systems to affect hippocampal and frontal cortical brain areas and thereby
      enhance memory, particularly at the retrieval stage.

PMID- 19401957
TI  - Does postmenopausal estrogen use confer neuroprotection?
AB  - Sex steroids modulate brain function at all developmental stages of life. This
      article focuses on the role of sex steroids after menopause with the intent of
      addressing the question whether or to what extent sex steroids, particularly
      estrogenic agents, are neuroprotective for the aging brain of women. The
      rationale for delving into this complicated topic is that the information and
      perspective so acquired will aid physicians in counseling surgically and
      naturally menopausal women about their therapeutic options. Whereas we review and
      synthesize relevant data from monkey, other animal, cellular, and molecular
      studies, the emphasis is on human studies and reconciling the disparate evidence.
      Although the knowledge gaps are considerable, available evidence suggests that
      extended use of non-oral estradiol is a reasonable course of action if the woman
      to be treated has a relatively low risk for cardiovascular disease and venous
      thromboembolism or a high concern about developing dementia. It is important to
      emphasize that estradiol may negatively impact an already unhealthy individual
      and yet synergize other health-promoting behaviors such as good nutrition,
      exercise, and stress reduction in a relatively healthy individual.

PMID- 19401958
TI  - Endogenous and exogenous estrogen, cognitive function, and dementia in
      postmenopausal women: evidence from epidemiologic studies and clinical trials.
AB  - There are more than 200 published scientific papers showing that estrogen has
      favorable effects on brain tissue and physiology in cell culture and animal
      models including non-human primates. The biological plausibility for a
      neuroprotective estrogen effect is overwhelming. However, most studies of
      endogenous estrogen and cognitive decline or dementia in women fail to show
      protection, and some suggest harm. Failure to find any consistent association
      might reflect the limitations of a single time of estrogen assay or poor assay
      sensitivity. More than half of the observational studies of hormone therapy
      suggest benefit. Nearly all long-term clinical trials fail to show benefit, and
      the longer trials tend to show harm. Failure to adequately adjust for self
      selection of healthier and wealthier women and publication bias could account for
      some, or all, of the protective effect attributed to estrogen in observational
      studies. Overall, the evidence does not convincingly support the prescription of
      early or late postmenopausal estrogen therapy to preserve cognitive function or
      prevent dementia.

PMID- 19401961
TI  - [Radiology: on its way to an "individualized" medicine].

PMID- 19401962
TI  - [CT-guided radiofrequency ablation of liver metastases from colorectal cancer].
AB  - BACKGROUND AND OBJECTIVE: Data on radiofrequency ablation (RFA) of liver
      metastasis has not been uniform. The goal of this study was to determine medium
      term success of CT-guided RFA of liver metastases from colorectal cancer.
      PATIENTS AND METHODS: 43 consecutive patients (27 men; aged 67+/-10 years) with a
      total of 87 liver metastases from colo-rectal cancer were included in this
      retrospective analysis. All patients underwent percutaneous RFA after first- or
      second-line chemotherapy. The mean follow-up period was 29.8 +/- 22.7 (4 - 85)
      months. Overall survival and local recurrence-free survival were determined using
      Kaplan-Meier curves. The effects of primary therapeutic success, number of
      lesions, maximum lesion size and sum of lesion diameters were assessed. RESULTS:
      In total, 83 lesions were treated during 56 interventions. Taking into account
      local recurrence and incomplete ablation 86.7 % of metastases were successfully
      ablated. The median survival was 46 months with estimated 1-, 3- and 5-year
      survival rates of 89.0 %, 66.2 % and 41.8 %, respectively. The median interval to
      hepatic tumor progression was 13 months after RFA. Survival was related to
      primary treatment success (p = 0.0353), number of lesions (p = 0.0050) and sum of
      lesion diameters (p = 0.0199). CONCLUSION: CT-guided RFA is an effective
      treatment of liver metastases from colorectal cancer. These data support the use
      of RFA in patients considered ineligible for surgery.

PMID- 19401959
TI  - Estrogens, episodic memory, and Alzheimer's disease: a critical update.
AB  - Estrogen-containing hormone therapy initiated during late postmenopause does not
      improve episodic memory (an important early symptom of Alzheimer's disease), and
      it increases dementia risk. Cognitive consequences of exogenous estrogen
      exposures during midlife are less certain. Observational evidence implies that
      use of hormone therapy at a younger age close to the time of menopause may reduce
      risk of Alzheimer's disease later in life. However, there are concerns that
      observational findings may be systematically biased. Partial insight on this
      critical issue may be gleaned from results of ongoing clinical trials involving
      midlife postmenopausal women (Early versus Late Intervention Trial with Estrogen;
      Kronos Early Estrogen Prevention Study). The effects of exogenous midlife
      estrogen exposures and Alzheimer risk can also be approached through better
      animal models, through carefully designed cohort studies, and through use of
      surrogate outcomes in randomized controlled trials in midlife women. Selective
      estrogen receptor modulators have the potential to affect cognitive outcomes and
      also merit additional study.

PMID- 19401963
TI  - [Multiple bilateral pulmonary nodes following breast cancer].
AB  - HISTORY AND ADMISSION FINDINGS: Multiple new pulmonary nodules were demonstrated
      at chest radiography in a 69-year-old woman who had been treated for breast
      cancer ten years previously. INVESTIGATIONS: Laboratory tests suggested mild
      inflammation. Pulmonary function tests demonstrated small airways disease. But
      because of an atypical morphology at computed tomography (CT), metastases were
      considered unlikely. CT-guided percutaneous biopsy revealed cryptogenic
      organizing pneumonia (COP). TREATMENT AND COURSE: Oral medication with decreasing
      doses of steroids resulted in clinical and radiological improvement. CONCLUSIONS:
      Even in a patient with known malignancy the differential diagnosis of multiple
      bilateral pulmonary nodules includes a variety of conditions and is meticulous,
      if necessary invasive diagnostic procedures are required.

PMID- 19401964
TI  - [Hilar cholangiocarcinoma (Klatskin's tumor): up-to-date radiologic diagnosis,
      intervention and treatment possibilities].
AB  - HISTORY AND ADMISSION FINDINGS: A 53-year-old man with jaundice was referred with
      suspected cholangiocarcinoma of the porta hepatis. He was found to be in a
      reduced general and nutritional condition. Cholinesterase was decreased, total
      bilirubin, GOT, GPT and alkaline phosphatase were increased. INVESTIGATIONS:
      Abdominal contrast-enhanced computed tomography revealed a centrally located and
      contrast-enhancing mass at the proximal common hepatic duct. Metastases were not
      detectable. Endoscopic retrograde cholangiography showed a stenosis of the
      proximal common hepatic duct. An additional magnetic resonance tomography with
      cholangio-pancreatography confirmed the centrally located tumor as well as the
      stenosis of the common hepatic duct. DIAGNOSIS, TREATMENT AND COURSE: The
      diagnostic tests were suggestive of a stage IV cholangiocarcinoma of the porta
      hepatis (Klatskin's tumor). The origin was subsequently proven histologically.
      There was no evidence of intra- or extrahepatic metastases. An interventional
      embolization of the right portal vein was performed preoperatively to stimulate
      the growth of the left hepatic lobe. But before surgery could take place a
      percutaneous transhepatic cholangiography and biliary drainage had to be done
      followed by an extended right-sided hemihepatectomy. During a 12 month follow-up
      no recurrence was observed. CONCLUSION: Klatskin's tumor is rare and requires
      interdisciplinary collaboration. Recent developments in diagnostic,
      interventional and surgical methods result in a better prognosis.

PMID- 19401965
TI  - [79-year-old man with progressive febrile infection after lung cancer resection].

PMID- 19401966
TI  - [Cardiac computed tomography].

PMID- 19401967
TI  - [Virtual colonoscopy for the detection of colorectal tumors--pro].

PMID- 19401968
TI  - [Virtual colonoscopy for the detection of colorectal tumors--contra].

PMID- 19401969
TI  - [Molecular imaging].

PMID- 19401970
TI  - [The diabetic foot syndrome: pathogenesis, diagnosis and interventional
      treatment].

PMID- 19401971
TI  - [Magnetic resonance cholangiopancreatography (MRCP) from a radiological and
      gastroenterological perspective].
AB  - Magnetic resonance imaging (MRI) in combination with magnetic resonance
      cholangiopancreatography (MRCP) is an integrated part in the diagnosis of bile
      duct diseases and requires a standaridized complex examination technique.
      Radiologic and gastroenterologic indications are the diagnosis of anomalies,
      concrements, chronic inflammations and tumor diagnosis, especially of
      cholangiocarinoma such as Klatskin tumor and pancreatic cancer. MRCP is
      integrated in the preinterventional concept for performing invasive endoscopic
      retrograde cholangiopancreatography (ERCP) and for follow-up post intervention
      and for diagnosing complications.

PMID- 19401973
TI  - Aneurysmal and non-aneurysmal SAH--is initial computed tomography predictive?
AB  - PURPOSE: Diagnostic workup in patients with angiographically negative
      subarachnoid hemorrhage (SAH) remains controversial. We discuss the relevance of
      bleeding patterns on CT as they pertain to the prediction of angiographic
      results. MATERIALS AND METHODS: We compared bleeding patterns on 112 CTs of
      patients with non-aneurysmal subarachnoid hemorrhage (non-ASAH) and 104 CTs of
      patients with aneurysmal SAH (ASAH) taken within 48 hours according to a CT-based
      grading system (Type 0 - 4). RESULTS: Bleeding patterns differed between ASAH and
      non-ASAH patients (p < 0.0001). Non-ASAH patients had no or prepontine blood
      (type 0 + 1) in 40% of cases, extension into the medial (type 2) or lateral (type
      3) Sylvian fissure in 60% of cases and no intracerebral hemorrhage (type 4). All
      type 0 and 1 patients had negative initial and repeat angiographies. CONCLUSION:
      A CT classification of bleeding patterns helps to predict angiographic results.
      Digital subtraction angiography (DSA) should remain the gold standard as it
      allows detection non-aneurysmal bleeding sources at low-risk. Repeat angiography
      may be omitted in the case of type 0 and 1 bleeding if a complete, high quality
      DSA was obtained initially.

PMID- 19401972
TI  - [Long-term outcome after endovascular treatment of high-risk patients with
      recurrently symptomatic intracranial stenoses of the posterior circulation].
AB  - PURPOSE: We present long-term clinical and duplex data from high-risk patients
      with severe, recurrent symptomatic stenoses of the vertebrobasilar circulation.
      We hypothesized that despite the greater risk of periprocedural complications in
      this patient group, interventional treatment would reduce the risk of recurrent
      strokes relative to the expected natural risk. We also predicted that the long
      term treatment outcome would be positively influenced by the use of stents and by
      the periprocedural technical success rate. MATERIALS AND METHODS: An analysis of
      our patient data base yielded 45 cases of stenosis of the vertebrobasilar
      circulation treated endovascularly in 42 patients between 1998 and 2006. Clinical
      and vascular diagnostic tests, both periinterventionally and during follow-up,
      were performed independently by experienced neurologists. RESULTS: The technical
      success rate was 93%. Stents were used in 67% of the procedures. After 30 days,
      24% of the patients showed post-procedural clinical deterioration. After an
      average period of 26.3 months, 17.8 % of the patients had deteriorated. 11.1% of
      the patients suffered severe permanent damage as a result of the procedure (mRs 3
      - 6). Restenosis was found in 9.5% of the cases. There were no instances of a
      recurrent stroke during follow-up. CONCLUSION: For this population of high-risk
      patients with recurrently symptomatic intracranial stenoses of the
      vertebrobasilar axis, endovascular treatment reduced the risk of stroke and death
      relative to the expected natural risk. The use of stents had no significant
      effect on the long-term results.

PMID- 19401974
TI  - [Endomyocardial fibrosis in chronic eosinophilic leukemia].

PMID- 19401975
TI  - [Case report of a rare cause of acute abdomen].

PMID- 19401976
TI  - [Endovascular therapy of a uretero-iliac prosthesis related fistula].

PMID- 19401977
TI  - [Isolated pre-coccygeal space occupying lesions as a rare manifestation of
      extramedullary hematopoiesis].

PMID- 19401978
TI  - [Multifocal pilocytic astrocytoma in infancy].

PMID- 19401980
TI  - B-cell lymphoma of the female breast: comparison of mammography, ultrasound and
      dynamic MRI.

PMID- 19401981
TI  - [Initial assessment and management of acute poisonings].
AB  - In Switzerland about 250 severe or fatal cases of poisoning occur annually in
      adults, and approximately 25 cases of pediatric poisoning (calls to the Swiss
      Toxicological Information Centre). Patients with life-threatening symptoms need
      immediate intensive care according to their symptoms, regardless whether the
      responsible cause is known or not. In these cases the emergency ABCDE (Airway,
      Breathing, Circulation, Disabilities, Exposure) is used. The investigation of the
      cause of poisoning (identification of the responsible agents) and additional
      tests including ECG, lab analyses, and x-rays are performed at the same time.
      Their results are continuously included into the management of the poisoned
      patient. It is essential that the treatment chosen does not negatively interact
      with the known or potential toxicant thus worsening the symptoms. Specific
      treatments are possible only if the underlying toxicants are known, or if a
      toxidrome reveals a substance group as underlying cause of the condition,
      required for a targeted treatment.

PMID- 19401979
TI  - Contrast-enhanced ultrasound for imaging of adrenal masses.
AB  - PURPOSE: The number of incidentally discovered adrenal masses is growing due to
      the increased use of modern high-resolution imaging techniques. However, the
      characterization and differentiation of benign and malignant adrenal lesions is
      challenging. This study aimed to evaluate contrast-enhanced ultrasound for the
      characterization of adrenal masses. MATERIALS AND METHODS: We studied 58 patients
      with adrenal masses detected with computed tomography, magnetic resonance
      imaging, or ultrasound. 7 patients had bilateral adrenal lesions. Contrast
      enhanced ultrasound was performed using high-resolution ultrasound (3.5 - 7 MHz)
      and intravenous injection of 2.4 ml SonoVue. The contrast enhancement pattern of
      all adrenal lesions was documented. RESULTS: The 18 malignant adrenal tumors were
      significantly larger at the time of diagnosis compared to the 40 benign lesions
      (p < 0.03). The majority of benign adrenal lesions (37 / 40) had a nonspecific
      type of contrast enhancement (24 / 40) or a peripheral to central contrast
      filling (13 / 40) described as the iris phenomenon. Similar findings were
      observed in malignant adrenal tumors: most malignant lesions also showed
      nonspecific (6 / 18) or peripheral to central contrast filling (9 / 18).
      Peripheral to central contrast filling had 50 % sensitivity (26 - 74 %) and 68 %
      specificity (51 - 81 %) for indicating malignancy. CONCLUSION: Contrast-enhanced
      ultrasound facilitates the visualization of vascularization even in small adrenal
      masses, but it does not help to distinguish malignant and benign lesions.

PMID- 19401982
TI  - [Decontamination and antidotes in acute cases of poisoning].
AB  - In acute poisoning the maintenance or reconstitution of vital functions is the
      first and most critical action. All subsequent therapies and the prognosis depend
      on the identification of the causative agent and on information about substance
      specific toxicity. Despite incomplete evidence the concept of harm reduction by
      decreased absorption of the toxicants and by shortening the course of illness is
      consistent with toxicokinetic-dynamic principles and is therefore still used by
      clinical toxicologists. All these treatment options have to be seen within the
      context of the prognosis and the time course of an individual case of poisoning.
      Treatment options of gastrointestinal decontamination are (in decreasing order of
      importance) single-dose activated charcoal, whole bowel irritation, and gastric
      lavage. Induced emesis by ipecac syrup is not practiced anymore. Enhanced
      elimination techniques are multiple-dose activated charcoal, urine
      alkalinization, and extracorporeal techniques such as hemodialysis and
      hemoperfusion. Enhanced elimination is only beneficial in toxicants with long
      half-life. Antidotes are directed against specific agents and therefore may be
      used only in a limited number of cases. The procurement of specific antidotes,
      often hardly available and not approved, is facilitated if the supply is
      organized in a transparent and standardized manner.

PMID- 19401984
TI  - [Intoxications with plants].
AB  - Ingestions of plants rarely lead to life-threatening intoxications. Highly toxic
      plants, which can cause death, are monkshood (Aconitum sp.), yew (Taxus sp.) and
      autumn crocus (Colchicum autumnale). Lethal ingestions of monkshood and yew are
      usually suicides, intoxications with autumn crocus are mostly accidental
      ingestions of the leaves mistaken for wild garlic (Allium ursinum). Severe
      intoxications can occur with plants of the nightshade family like deadly
      nightshade (Atropa belladonna), angel's trumpet (Datura suaveolens) or jimsonweed
      (Datura stramonium). These plants are ingested for their psychoactive effects.
      Ingestion of plant material by children most often only causes minor symptoms or
      no symptoms at all, as children usually do not eat great quantities of the
      plants. They are especially attracted by the colorful berries. There are plants
      with mostly cardiovascular effects like monkshood, yew and Digitalis sp. Some of
      the most dangerous plants belong to this group. Plants of the nightshade family
      cause an anticholinergic syndrome. With golden chain (Laburnum anagyroides),
      castor bean (Ricinus communis) and raw beans (Phaseolus vulgaris) we see severe
      gastrointestinal effects. Autumn crocus contains a cell toxin, colchicine, which
      leads to multiorgan failure. Different plants are irritative or even caustic to
      the skin. Treatment is usually symptomatic. Activated charcoal is administered
      within one hour after ingestion (1 g/kg). Endoscopic removal of plant material
      can be considered with ingestions of great quantities of highly toxic plants.
      Administration of repeated doses of charcoal (1-2 g/h every 2-4 hours) may be
      effective in case of oleander poisoning. There exist only two antidotes: Anti
      digoxin Fab fragments can be used with cardenolide glycoside-containing plants
      (Digitalis sp., Oleander). Physostigmine is the antidote for severe
      anticholinergic symptoms of the CNS. Antibodies against colchicine, having been
      developed in France, are not available at the moment.

PMID- 19401983
TI  - [Poisoning with antidepressants].
AB  - Intoxications with medications are among the most frequent diagnoses in patients
      admitted to medical emergency departments and intensive care units. Due to their
      particular toxicity tricyclic antidepressants play an important role despite a
      decreasing incidence. Tricyclic antidepressant toxicity includes an inhibition of
      myocardial excitability, central (sedation, seizures) and peripheral
      anticholinergic signs, and arterial hypotension. Cardiac arrhythmia including
      ventricular tachycardia and fibrillation, sustained seizures and severe central
      anticholinergic symptoms such as agitation, delirium, and hyperthermia, are life
      threatening. Important treatment options include gastrointestinal decontamination
      with oral single-dose activated charcoal within 1-2 hours post ingestion, and
      antidotal therapy with boluses of sodium bicarbonate for cardiotoxicity. The
      selective serotonin reuptake inhibitors (SSRI) and the atypical antidepressants
      are far less toxic than tricyclics. They may lead to serotonin toxicity
      (serotonin syndrome).

PMID- 19401985
TI  - [Accidents with venomous and poisonous animals in Central Europe].
AB  - Central Europe is largely safe from accidents with venomous and poisonous
      animals. The regions where European vipers are regularly found are shrinking.
      Today accidents with jellyfish and stings of venomous fish afflicted during
      leisure activities at the sea side play the dominant role. Life threatening
      accidents in Europe are mainly due to exotic snakes held in captivity. A system
      useful in daily medical practice is explained to classify and stage accidents due
      to poisonous and venomous animals. The important poisonous and venomous animals
      of Central Europe and the specific therapeutics, the antivenoms, are covered. The
      antivenom depot "Antivenin-CH" of the Swiss Toxicology Information Centre in
      Zurich and the MRITox in Munich with the antivenom registry Munich AntiVenom
      INdex (MAVIN) are presented.

PMID- 19401986
TI  - [Mushroom poisoning--the dark side of mycetism].
AB  - Most mushroom intoxications become evident within 12 hours with vomiting and
      diarrhea. They can be divided into incidents with a short latency (less than four
      hours) and incidents with a long latency (longer than four hours). As a rule of
      thumb amatoxin poisonings must be considered in case of symptoms appearing with a
      long latency (8-12-18 h), especially after consumption of non-controlled wild
      mushrooms. Shorter latencies do not exclude amatoxin poisoning. Large meals of
      mushrooms, which are rich in chitin, mixed meals and individual factors, may
      shorten latency and disguise amatoxin poisoning. Any vomiting and diarrhea after
      mushroom consumption is suspicious. Unless the mushrooms are not to be identified
      within 30 minutes by an expert, specific treatment for amatoxin poisoning must be
      started. Identification shall be achieved by macroscopic or microscopic means;
      and urine analysis for amatoxins are crucial. By commencing treatment before
      analysis, mortality rates may be as low as 5%. Current standards in amatoxin
      poisoning treatment can be obtained at the Swiss Toxicological Information Centre
      (Phone 145), where contacts to mycologists are available as well. Emergency
      mycologists are listed on the website www.vapko.ch. Of the 18 different syndromes
      we present the most common and most important in Switzerland. In an overview all
      of them are listed. Early gastrointestinal syndrome with its short latency of
      less than 4 h and indigestion with a very variable latency are the most common.
      Psychotropic symptoms after consumptions of fly agaric and panther cap are rare,
      in case of psilocybin-containing mushrooms, symptoms are frequent, but hardly
      ever lead to medical treatment. In case of renal failure and rhabdomyolysis of
      unknown origin, completing a patient's history by questioning nutritional habits
      might reveal causal relationship with ingestion of orellanin-containing mushrooms
      or tricholoma equestre respectively. Mushrooms in the backyard are attractive for
      children. We discuss possible approaches.

PMID- 19401987
TI  - [Laboratory investigations in acute intoxications--what makes sense?].
AB  - Clinical symptoms in acute intoxications are often nondescript and unspecific for
      a definite diagnosis. This makes laboratory investigations necessary in order to
      initiate supportive measures and to confirm or discard the diagnosis of an acute
      intoxication. For toxicological analyses immunoassays as well as chromatographic
      methods are applied. Unfortunately, not all potential toxic compounds can be
      detected by these methods, e.g. ethanol and metals (including lithium) cannot be
      seen. The sample materials for toxicological analyses are on one hand blood for
      the quantitative determination of a distinct compound and on the other hand urine
      for toxicological screening procedures. Whenever the clinical situation does not
      exclude intoxication, a toxicological screening should be carried out. The
      comprehensiveness of the toxicological screening is dependent on the anamnesis
      and the clinical symptoms of the patient and should also depend on the
      therapeutic options for the various differential diagnoses. A specific
      quantitative determination of the toxic compound is recommended for
      acetaminophen, lithium, amanitine (intoxications with death cap), colchicine,
      alcohols and glycols, carbon monoxide and cyanide.

PMID- 19401988
TI  - [Pediatric poisoning, with special reference to household products].
AB  - Poisoning in children with household products are common. The majority of these
      accidents are of low severity and resolve without complications. The big
      challenge for physicians is to reveal the few situations that could be life
      threatening where immediate interventions is needed. The most commonly
      encountered substances in household products are detergents, alcohols (ethanol,
      isopropanol), hydrocarbons, as well as irritants (bleach, limescale removers).
      Rare but dangerous chemicals are for example "toxic alcohols" (methanol, ethylene
      glycol) and strong acids and alkalis. Also in case of ingestion of button
      batteries or magnets severe cases are uncommon but each case must be judged
      carefully to identify the cases where complications could appear.

PMID- 19401989
TI  - [Caustic injuries of the eye, skin and the gastrointestinal tract].
AB  - Caustic injuries of the eye usually occur accidentally and can result in minor
      eye irritations to total loss of vision. All chemical exposures to the eye
      require immediate decontamination by copious irrigation with an aqueous solution
      for at least 15-30 minutes up to two hours in single cases of massive exposure.
      Tap water is readily available, safe, and effective and, thus, the preferred
      irrigation fluid. Warmed lactated Ringer's solution is theoretically preferable
      to normal saline as an ocular irrigant because it has a more physiologic pH and
      osmolarity. Immediate ophthalmologic referral is recommended for all but the most
      trivial chemical burns to the eye. Specific treatments for decontamination depend
      on the underlying agent. Chemical burns of the skin usually occur accidentally.
      Initial treatment consists of copious water lavage commencing at the scene and
      removal of particles. While most caustic injuries are treated symptomatically,
      exposures to hydrofluoric acid (HFA) frequently necessitate specific topic,
      subcutaneous, intralesional, intravenous or intraarterial injections of calcium
      gluconate to bind fluoride ions until analgesia. A burn from HFA that involves
      more than 5% of total body-surface area, or more than 1% of total body-surface
      area if the concentration of HFA is greater than 50%, requires admission to an
      ICU for electrocardiographic monitoring and serial measurements of calcium
      levels, since life-threatening arrhythmias and hypocalcemia can occur. Caustic
      injuries of the gastrointestinal tract can occur due to inadvertent ingestion of
      mislabelled fluids or as a suicidal attempt. Ingestion of alkalis is generally
      thought to result in more severe injuries than ingestion of acids. The oropharynx
      needs to be first examined by laryngoscopy. A supraglottic or epiglottic burn
      with erythema and edema formation may be a harbinger of airway obstruction and
      should be seen as an indication of early endotracheal intubation or tracheostomy.
      Endoscopy should be performed preferably within 12 hours and generally not later
      than 24 hours and can serve as a prognostic tool to manage patients
      appropriately. The risk of procedure related perforation is generally accepted to
      be negligible. Existing data fail to support the routine use of steroids and
      antibiotics to prevent esophageal stricture formation and may mask signs of
      peritonitis. Esophageal strictures, stenosis or gastric outlet obstruction are
      formidably long-term complications. There is a 1000- to 3000-fold increase in the
      incidence of esophageal carcinoma after lye-ingestion with a latent period
      between the time of ingestion and the development of carcinoma as long as 60
      years. Endoscopic dilatation or insertion of intraluminal stents should not be
      performed within the first 6 weeks. Patients with grade 3b injuries may underwent
      prompt surgical resection in single cases, even if no perforation is confirmed.
      Perforation, evolution of a mediastinitis or peritonitis with multi-organ failure
      are devastating complications with extremely high mortality and warrants
      immediate surgical treatment.

PMID- 19401990
TI  - [Acute poisoning with carbon monoxide (CO) and cyanide (CN)].
AB  - A critical analysis of acute CO and CN poisonings evidences that the lone
      toxicological similarity between CO and CN is their ability to avidly bind iron
      ions in the different hemoproteins. Otherwise, CO is a stable not-metabolized
      molecule while CN is a highly reactive molecule with extensive metabolism. CO
      impairs the ability of erythrocytes to transfer oxygen while CN has no effect.
      Both toxicants act in the mitochondria with CN resulting in the complete and
      sustained blockade of cellular respiration inducing severe lactic acidosis while
      CO does not. Acute CO poisoning mostly alters neurological cognitive function and
      even consciousness without significant alteration of vital functions while CN
      primarily alters consciousness with early onset of severe alteration of vital
      functions. Severe CO poisonings requires hours of exposure while severe CN
      poisoning occurs within seconds or minutes of exposure. Both gases may result in
      brain damage and sequelae. Brain imaging clearly shows significant differences in
      the locations and types of CO- and CN-induced brain damages, further supporting
      different mechanisms of action. Oxygen is the lone treatment of CO poisoning
      while in CN poisonings antidotes associated to oxygen are more efficient than
      oxygen alone. Unfortunately, there are several conditions where the easily
      detected and potentially toxic CO still continues to mask other potent toxicants.
      The lack of awareness of emergency physicians, clinical toxicologists, and
      neuroradiologists regarding the role of other toxic gases whose important role is
      recognized in combustion toxicology or environmental medicine precludes any
      progress in the understanding of the mechanisms of toxicity and in the treatment
      of these poisonings resulting in a particularly high rate of morbi-mortality.

PMID- 19401993
TI  - [Improved health services for mentally ill children and adolescents].

PMID- 19401994
TI  - [Research in child and adolescent psychiatry, promotion of young academics and
      publication practice].
AB  - Objective is the promotion of the international recognition of research in child
      and adolescent psychiatry which is published in German language. There is a
      necessity for change of the strategy of publication in these scientific journals.
      The goal is to increase the impact factor. The length of the review and
      publication process has to be shortened, citations should be relevant to the
      present, interdisciplinarity and the cooperation of the editorial boards of
      different disciplines should be reinforced. These efforts are necessary for a
      better international recognition of publications in German language.

PMID- 19401995
TI  - [Medical teaching in the area of conflict between "Evidence-based Medicine" and
      "Experience-based Medicine"].
AB  - As a medical discipline Child and Adolescent Psychiatry and Psychotherapy has
      gained increasing importance within society since given the epidemiological
      importance of behavioural problems in childhood and adolescence, it has
      verifiably improved the developmental chances of children at high risk. Child and
      Adolescent Psychiatry and Psychotherapy therefore should be systematically
      integrated into the German Medical Curriculum. The bio-psycho-social model
      provides us with a comprehensive paradigm of psychiatric disorders and has to
      face the problem of hermeneutics. An equilibrium between Evidence-based Medicine
      and the individual clinical experience with patients (Experience-based Medicine)
      must be established within medical teaching, rather than playing one against the
      other. Ethical dilemmas of medical therapy have to be taken into account.

PMID- 19401996
TI  - [Introduction of the module "Evidence-based Medicine" in Child and Adolescent
      Psychiatry into the psychiatry block practicum at the University of Ulm].
AB  - OBJECTIVE: The essential need for the timely availability of additional relevant
      information has resulted in a focus on "Evidence-based Medicine" (EBM) in medical
      practice. In Child and Adolescent Psychiatry (CAP) training it is essential to
      impart knowledge of how to effectively use the available literature, since the
      evidence for many therapies is still poor. METHOD: We modified the "Duke Model"
      for teaching EBM in CAP to better attune it to the educational needs of a German
      university. We describe the introduction of the teaching module "Evidence-based
      Medicine in CAP" in practical clinical training. RESULTS: Integrating EBM into
      mandatory practical training enables the students to deal with problems that
      directly pertain to patient treatment, thus motivating them to access and read
      relevant scientific literature. An initial evaluation of this pilot project shows
      the successful linkage of research with clinical routine and also the conveyance
      of improved decision making abilities as well as an attitude of life-long
      learning. CONCLUSIONS: Modifying the EBM-module for practical clinical training
      is an innovative approach to integrating EBM into medical curricula. In the
      course of a curricular reform, "EBM cross sectional training" for all medical
      students was introduced into the new curriculum of the Medical School at the
      University of Ulm.

PMID- 19401998
TI  - [Docs'n Drugs--an E-learning program for medical students; feasibility and
      evaluation of the acceptance in student training in child and adolescent
      psychiatry at the University Hospital in Ulm].
AB  - OBJECTIVE: Increasingly widespread is the use of modern media such as E-learning
      in medical education. The Medical Faculty of the University of Ulm, being the
      Competence Center of E-learning, and the Competence Network in Medical Education
      in Baden-Wurttemberg have been developing a web based multimedia educational
      program since 1998. METHODS: In 2004 a grant for modular teaching projects
      sponsored by the Medical School was obtained in order to incorporate cases from
      Child and Adolescent Psychiatry into the Docs'n Drugs E-learning Module. The
      objective was to explore the feasibility of adding psychiatric cases to an
      educational system that was primarily oriented towards somatic diseases and to
      then evaluate the acceptance of these child and adolescent psychiatric cases.
      RESULTS: Once cases had been developed, this module was integrated into Docs'n
      Drugs as a one-and-a-half hour web-based seminar as part of a block practicum in
      child and adolescent psychiatry and subsequently evaluated. The evaluation
      included data from 69 participants between summer 2004 and spring 2006. Of the
      participating students, 80.8% had never used the E-learning platform together
      with a monitor in a seminar before. 44.9%, respectively 41%, of the students
      responded that psychiatric cases could be dealt with in a good or partially
      satisfying way with that system. This gives an overall positive acceptance of
      86%. CONCLUSIONS: Our evaluated feasibility trial with a child psychiatric module
      within an E-learning based teaching platform showed that knowledge not only of
      somatic cases but also of psychiatric cases can be imparted via E-learning. The
      integration into an existing curriculum is advisable in any case.

PMID- 19401997
TI  - [Child and Adolescent Psychiatry (CAP) in the "Heidelberg Curriculum Medicinale"
      (HeiCuMed)--practice-oriented learning in the reformed course of studies].
AB  - To improve medical studies, the Medical School of the University of Heidelberg
      introduced in 2001 a new modular, topic-oriented curriculum for approximately 260
      students with a special focus on multi-disciplinarity, thus breaking the seal of
      traditional disciplines. The new curriculum (Heidelberg Curriculum Medicinale-
      HeiCuMed) introduced new methods of teaching and in addition to the traditional
      examinations, developed new methods of testing clinical-practical, respectively
      communication skills, such as the Objective Structured Clinical Examination
      (OSCE). Child and Adolescent Psychiatry gained greater importance within the new
      curriculum and courses are now mandatory. Particularly the new methods of
      teaching provide an opportunity to make studies in Child and Adolescent
      Psychiatry even more attractive to students and to strengthen the position of the
      discipline within the schools of medicine.

PMID- 19401999
TI  - [What do medical students learn in the elective course in Child and Adolescent
      Psychiatry?].
AB  - OBJECTIVE: A course in child and adolescent psychiatry and psychotherapy is
      optional for medical students within the Medical Curriculum Munich (MeCuMLMU).
      Aims of the course are to give insight into the specialty of child and adolescent
      psychiatry and to help students acquire basic skills. The focus is on
      psychopathology and on communication skills. METHOD: A course comprising 23
      teaching units and limited to twelve students is taught over four days within one
      week twice per semester. Child and Adolescent Psychiatry is introduced by means
      of case presentations of children in different age groups, each with
      externalizing, and internalizing disorders and with developmental delay, and by a
      clinical round in the teaching hospital affiliated to the University. Case
      examples of children are presented by video. In group discussions guided by a
      teacher students learn to formulate a psychopathological status. Role-plays
      derived from the clinical examples and video-based feed-back provides students
      with the opportunity to improve their communication skills. RESULTS: The course
      is evaluated by means of a written examination, in which a psychopathological
      status must be written down independently. Students and teachers evaluate the
      seminar in a structured way. Videotapes of the role-plays are analyzed by the
      teachers after the course. In a sub-sample, a follow-up evaluation was carried
      out six months later. CONCLUSIONS: The seminar offers an excellent opportunity to
      introduce medical students to child and adolescent psychiatry and to recruit and
      inspire a future generation of child and adolescent psychiatrists.

PMID- 19402000
TI  - [A good care of students in their residency (PJ students)--a win-win-situation].
AB  - The provision of good mentors and education to medical students in their
      residency (PJ students) bears three essential advantages: 1) If the students feel
      themselves in good hands, they will co-operate effectively, thereby reducing the
      burden of the medical staff. 2) Contented students are potential advertisers for
      other interns, clinical trainees, medical students in residency and Ph.D.
      students. 3) Given the lack of doctors, providing students with good mentors and
      training is a valuable long-term strategy for the recruitment of doctors; in the
      event of later employment, former students in residency represent employees who
      are motivated, well trained, and familiar with hospital routine--a classical win
      win situation.

PMID- 19402001
TI  - [Breaking bad news--a video-based training unit for medical students].
AB  - OBJECTIVE: In 2002, the Medical Licensing Board prescribed fundamental changes in
      medical education. The reformed curriculum set its focus on bed-side teaching in
      small groups, problem-based courses, and training of communication skills. The
      previous curriculum did not include the teaching of communication skills to
      future physicians. Physicians thus felt unprepared for the doctor-patient
      communication. METHOD: Within the newly derived Medical Curriculum Munich
      (MeCuMLMU), the School of Medicine at the Ludwig-Maximilian-University of Munich
      implemented in 2005 a teaching unit named "Breaking Bad News" in order to train
      the students' communication skills. Its main elements are videotaped role-plays
      and the subsequent video-based analyses. In the role-plays, students experience
      the parts of a physician and a couple of parents. The task of the physician is to
      break the news of a severe condition to the parents of a child. The teaching
      units are held by members of the department of child psychiatry together with
      fifteen members of the department of paediatrics who had been instructed in
      analyzing videotaped role-plays. A manual was developed to facilitate a
      standardized approach. RESULTS AND CONCLUSIONS: The teaching units were evaluated
      by means of questionnaires filled in by students and tutors. The evaluation
      showed that "Breaking Bad News" was highly appreciated by both students and
      tutors. Our experience showed that this type of instruction is suitable to
      improve the communication skills of medical students, and it is feasible despite
      the relatively extensive technical and personnel resources needed.

PMID- 19402018
TI  - [Depersonalisation/derealization - clinical picture, diagnostics and therapy].
AB  - The present state of knowledge about depersonalization (DP) and derealization
      (DR) is reviewed with respect to classification, epidemiology, etiology, and
      therapy. Mild and transient DP-DR are considered to be common phenomena. The
      prevalence of depersonalization-derealization disorder (DP-DR-D) is estimated to
      be approx. 1-2% of the general population in the Western hemisphere. DP-DR-D is
      probably severely underdiagnosed. DP-DR-D is strongly associated with depression
      and anxiety disorders. It is suggested that symptoms of DP-DR indicate disease
      severity and negatively predict therapy outcome. Neurobiological and
      psychological models have shown that a disordered body schema and emotional and
      autonomic blunting are essential components of the disorder. Despite the
      frequency of DPDR and its clinical relevance, there is a considerable lack of
      empirical research on DP-DR with respect to the health-care situation of
      depersonalized patients and with regard to treatment options.

PMID- 19402019
TI  - [Course of psychosocial distress and health-related quality of life in patients
      at different age groups during cancer rehabilitation].
AB  - OBJECTIVES: This study investigates psychosocial distress and health-related
      quality of life in younger (up to 40 years), middle-aged (up to 50 years), and
      elderly cancer patients (up to 60 years). METHODS: 637 patients (94%women, 75%
      breast-cancer patients) completed validated questionnaires measuring distress,
      anxiety, depression, fear of progression, and quality of life at the beginning
      (T0) and the end (T1) of a cancer rehabilitation program (T0/T1 response rate: 72
      %) as well as at 1-year follow-up (T2) (n = 485, T2 response rate: 76 %).
      RESULTS: Patients in the different age groups did not differ significantly in
      psychosocial distress at T0 except for fear of progression, which is lower among
      the younger age group. Elderly patients have a significantly lower physical
      quality of life. At the beginning of the rehabilitation program, patients in all
      age groups were significantly more anxious compared to population-based normative
      values, whereas higher depression was found only in younger and middle-aged
      patients. Patients in all age groups have a significantly lower quality of life
      compared to population-based normative values. In particular, large effect sizes
      were found for physical functioning domains. Patients in all age groups improve
      significantly in psychosocial distress and quality of life over time; however,
      significant interaction effects between age group and time were not observed in
      psychosocial distress and quality of life. CONCLUSIONS: Age differences are
      predominantly observed in physical quality-of-life dimensions rather than in
      psychosocial distress. This finding should be considered for the development of
      rehabilitation services.

PMID- 19402020
TI  - [Psychometric analysis of a short form of the "Hamburg Modules for the Assessment
      of Psychosocial Health" (HEALTH-49)].
AB  - OBJECTIVES: The HEALTH questionnaire, which originally consisted of 79 items,
      aims to assess generic aspects of psychosocial health. METHODS: Based on large
      clinical and healthy samples (n = 1548 psychotherapy inpatients, n = 5630 primary
      care patients), the questionnaire was shortened and psychometrically analyzed.
      RESULTS: The resulting 49-item questionnaire ("HEALTH-49") comprises six discrete
      modules with nine scales (somatoform complaints, depressiveness, phobic anxiety,
      psychological wellbeing, interactional problems, self-efficacy, activity and
      participation, social support, and social stress). It proves to be well accepted
      and feasible under routine conditions. Factor analyses confirm the intended
      dimensional configuration and the relative independence of modules. The scales
      reveal high reliability. Evidence of their validity and sensitivity to change are
      demonstrated. CONCLUSIONS: The HEALTH-49 is a self-rating instrument that allows
      for the comprehensive and economic assessment of generic aspects of psychosocial
      health. It is highly suitable for use in clinical practice. The questionnaire is
      available as a free download from http://www.hamburger-module.de/

PMID- 19402021
TI  - [Social phobia - the blind spot: infrequently diagnosed, highly complex, and a
      predictor for unfavourable therapy outcomes?].
AB  - OBJECTIVES: The objectives of the study were to examine (1) whether patients with
      social phobia report higher symptom load at the beginning and at the end of
      treatment and 1 year after treatment; and (2) whether the presence of social
      phobia is a factor that influences the course of treatment. METHODS: 613 patients
      from a university hospital for psychosomatic medicine filled out questionnaires
      assessing symptom load (SCL 90-R, KOPS), physical symptoms, psychological and
      social impairment (KOPS), and depression (BDI). Social phobia was diagnosed based
      on a standardized diagnostic interview. RESULTS: 25%of the patients suffered from
      social phobia. They had significantly more concurrent mental disorders (4.18 vs.
      2.41) and a higher symptom load than patients suffering from other mental
      disorders. They reported more physical complaints and depression and felt more
      impaired psychologically as well as socially. Even though both groups of patients
      profited from the treatment, compared to other patients, social phobia patients
      still had higher symptom load, impairment, and depression scores at the end of
      treatment and even at the follow-up 1 year after treatment. DISCUSSION: Social
      phobia is a severe disorder in which concurrent disorders frequently cause a high
      level of distress and impairment. These patients may benefit more from longer
      courses of treatment and/or disorder-specific treatment elements. Diagnostic and
      therapy approaches tailored to the generalized type of social anxiety are
      discussed.

PMID- 19402022
TI  - [Effectiveness of inpatient psychodynamic psychotherapy: a follow-up study].
AB  - OBJECTIVES: This study investigates the stability of symptomatic and
      interpersonal changes after inpatient psychodynamic psychotherapy. METHODS: 437
      patients were assessed 3 to 5 years after discharge with the Symptom Checklist
      (SCL-90-R), the Inventory of Interpersonal Problems (IIP), global assessment of
      effectiveness and utilization of posttreatment psychotherapy. The therapist's
      perspective was evaluated by the Impairment Severity Score (BSS), the Global
      Assessment of Functioning Scale (GAF), and the Clinical Global Impressions (CGI).
      RESULTS: Patients improved in all SCL-90-R scales significantly. The Global
      Severity Index (GSI) effect size was 0.81 posttreatment and 0.82 at follow-up.
      All IIP scales improved significantly; effect size of IIP total score was 0.40 at
      posttreatment and 0.60 at follow-up. There were substantial gains in BSS,GAF, and
      CGI. 84% of the patients were in psychotherapy after dismissal. DISCUSSION:
      Posttreatment results were in accordance with comparable studies. The results are
      stable on a symptomatic level and improve further on an interpersonal level.

PMID- 19402023
TI  - Complete 1H and 13C NMR assignments of four new oligosaccharides and two new
      glycosides from Periploca forrestii.
AB  - Four new oligosaccharides (1-4), one new pregnane glycoside (5), and one new
      cardiac glycoside (6) were isolated from the roots of Periploca forrestii Schltr.
      (Asclepiadaceae), a traditional Chinese medicine used for the treatment of
      rheumatoid arthritis and wounds. Their structures were characterized on the basis
      of extensive analysis of NMR (1H, 13C NMR, 1H-1H COSY, HSQC, HMBC, TOCSY and
      ROESY) spectra.

PMID- 19402024
TI  - Mutagenesis and molecular modeling of the orthosteric binding site of the mGlu2
      receptor determining interactions of the group II receptor antagonist (3)H-HYDIA.
AB  - Binding of the mGlu2/3 antagonist HYDIA in the closed conformation model of mGlu2
      causes repulsive interactions with Y216 in lobe II of the binding pocket,
      preventing closure of the VFT.Modulation of metabotropic glutamate 2/3 receptors
      represents a promising target for the treatment of neuropsychiatric disorders
      such as schizophrenia and depression. The novel mGlu2/3 ligand HYDIA
      ((1S,2R,3R,5R,6S)-2-amino-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid)
      is a conformationally restricted and hydroxylated glutamate analogue. HYDIA is a
      potent and selective competitive antagonist of L-glutamate at the mGlu2/3
      receptors in spite of being structurally very similar to the bicyclic LY354740,
      which is a potent and selective mGlu2/3 agonist. By comparing these two ligands,
      this study delineate the interaction mode of (3)H-HYDIA at the mGlu2 receptor,
      using both mutagenesis studies and computational modeling. Binding of HYDIA in
      the closed conformation model of mGlu2 results in repulsive interaction with the
      Y216 residue, preventing closure of the binding pocket and thus receptor
      activation. Consequently, HYDIA is proposed to bind in an open conformation model
      of mGlu2. Mutation of the structurally important Y216 residue in the binding site
      caused complete loss of affinity of both (3)H-LY354740 and (3)H-HYDIA. T168 in
      lobe I was shown to have an important role in HYDIA binding, and in the open
      conformation model this residue is interacting with the amino group of HYDIA. The
      Y144 residue in lobe I is shown to be engaged in both receptor interlobe binding
      and ligand interaction. Receptor mutations at this position (Y144G, Y144S and
      Y144A) showed dramatic impact on binding affinity and functional effect of HYDIA.
      The mGlu2 receptor mutants with increased structural flexibility at this
      position, which is crucial for pocket closure, were clearly preferred. These
      studies highlight the unique properties of the novel (3)H-HYDIA ligand and
      provide further support to our understanding of binding and signal transduction
      mechanisms of the mGlu2 receptor.

PMID- 19402025
TI  - Hierarchical additive modeling of nonlinear association with spatial correlations
      -an application to relate alcohol outlet density and neighborhood assault rates.
AB  - Previous studies have suggested a link between alcohol outlets and assaults. In
      this paper, we explore the effects of alcohol availability on assaults at the
      census tract level over time. In addition, we use a natural experiment to check
      whether a sudden loss of alcohol outlets is associated with deeper decreasing in
      assault violence. Several features of the data raise statistical challenges: (1)
      the association between covariates (for example, the alcohol outlet density of
      each census tract) and the assault rates may be complex and therefore cannot be
      described using a linear model without covariates transformation, (2) the
      covariates may be highly correlated with each other, (3) there are a number of
      observations that have missing inputs, and (4) there is spatial association in
      assault rates at the census tract level. We propose a hierarchical additive
      model, where the nonlinear correlations and the complex interaction effects are
      modeled using the multiple additive regression trees and the residual spatial
      association in the assault rates that cannot be explained in the model are
      smoothed using a conditional autoregressive (CAR) method. We develop a two-stage
      algorithm that connects the nonparametric trees with CAR to look for important
      covariates associated with the assault rates, while taking into account the
      spatial association of assault rates in adjacent census tracts. The proposed
      method is applied to the Los Angeles assault data (1990-1999). To assess the
      efficiency of the method, the results are compared with those obtained from a
      hierarchical linear model.

PMID- 19402026
TI  - Overview of the physical state of proteins within cells.
AB  - Proteins, the end product of gene expression, play a pivotal role in cellular
      structure and function. To understand how proteins work it is necessary to
      understand their physical state within the cell. This unit reviews the
      classification of proteins, how that is related to the hydropathicity of the
      protein, other factors that affect the heterogeneity of proteins, protein
      assemblies, methods for altering the solubility of proteins, and limitations of
      in vitro manipulations of proteins.

PMID- 19402027
TI  - Score test for age at onset genetic linkage analysis in selected sibling pairs.
AB  - A new score statistic is derived, which uses information from registries (age
      specific incidences) and family studies (sib-sib marginal correlation) to weight
      affected sibling pairs according to their age at onset. Age at onset of sibling
      pairs is modelled by a gamma frailty model. From this model we derive a bivariate
      survival function, which depends on the marginal survival and on the marginal
      correlation. The score statistic for linkage is a classical nonparametric linkage
      (NPL) statistic where the identical by descent sharing is weighted by a
      particular function of the age at onset data. Since the statistic is based on
      survival models, it can also be applied to discordant and healthy sibling pairs.
      Simulation studies show that the proposed method is robust and more powerful than
      standard NPL methods. As illustration we apply the new score statistic to data
      from a breast cancer study.

PMID- 19402028
TI  - Meta-analysis of the effectiveness of psychological and pharmacological
      treatments for binge eating disorder.
AB  - OBJECTIVE: The aim of this study was to compute and compare mean effects of
      various treatments for binge eating disorder. METHOD: A total of 38 studies with
      1973 participants fulfilled the defined inclusion criteria. Effect sizes, odds
      ratios, and simple rates were integrated in fixed and random (mixed) effects
      categorical models. RESULTS: From randomized controlled trials, psychotherapy and
      structured self-help, both based on cognitive behavioral interventions, were
      found to have large effects on the reduction of binge eating. Regarding
      pharmacotherapy, mainly comprising antidepressants, randomized controlled trials
      revealed medium effects for the reduction of binge eating. Uncontrolled studies
      on weight-loss treatments demonstrated moderate reductions of binge eating.
      Combination treatments did not result in higher effects compared with single
      treatment regimens. Except for weight-loss treatment, none of the interventions
      resulted in a considerable weight reduction. DISCUSSION: Psychotherapy and
      structured self-help, both based on cognitive-behavioral interventions, should be
      recommended as the first-line treatments.

PMID- 19402029
TI  - Cultural consequences of miscarriages of justice.
AB  - Social science scholarship has tended to focus more on the causes than the
      consequences of miscarriages of justice. Within the literature on consequences,
      the overwhelming emphasis has been on individual consequences: psychological and
      material impacts on the wrongly convicted individual and, in some cases, other
      indirectly impacted individuals such as family members of the wrongly convicted
      and victims of the true perpetrator's future crimes. Some attention has been
      devoted to social harms, the impact of miscarriages of justice on the broader
      society within which they are situated, such as the undermining of the legitimacy
      of the criminal justice system. This paper focuses on what are called here
      cultural consequences of miscarriages of justice: the way in which some high
      profile miscarriages of justice can shape the public's beliefs about some of the
      most basic "facts" about crime, such as the nature, prevalence, or even existence
      of certain categories of crime and the types of individual who tend to perpetrate
      particular types of crime. In this way, the paper argues, miscarriages of justice
      may have hitherto underexplored consequences: reshaping, based on false premises,
      the public's belief about the very nature of crime itself. This paper discusses
      three cases studies of miscarriages of justice that for varying periods of time
      created widespread false beliefs about the nature of crime in large segments of
      the public. The paper concludes by noting that the "righting" of these false
      beliefs was in most cases fortuitous. This suggests that unexposed miscarriages
      of justice may still be shaping popular beliefs about the nature of crime, and
      aspects of the public's current conception of crime may yet be based on false
      premises.

PMID- 19402030
TI  - Cluster randomized trials to study the comparative effectiveness of therapeutics:
      stakeholders' concerns and recommendations.
AB  - PURPOSE: To describe the concerns raised by health plan members, providers and
      purchasers related to studying the comparative effectiveness of therapeutics
      using cluster randomized trials (CRTs) within health plans. An additional goal
      was to develop recommendations for increasing acceptability. METHODS: Eighty-four
      qualitative in-depth telephone interviews were conducted; 50 with health plan
      members, 21 with providers, and 13 with purchasers. Interviews focused on
      stakeholders' concerns about and recommendations for conducting CRTs in health
      plans. RESULTS: Members expressed concerns that CRTs might compromise their
      healthcare. Providers and purchasers recognized the value of and the need for
      comparative effectiveness research. Providers expressed concerns that they would
      not have sufficient time to discuss a CRT with patients, and that participation
      in such a study could negatively impact their relationships with patients.
      Purchasers would want assurances that study participation would not result in
      members receiving lesser care, and that benefits would remain equitable for all
      members. CONCLUSIONS: This study provides insight into how health plan members,
      providers and purchasers might react to a CRT being conducted in their health
      plan. The recommendations reported here provide guidance for researchers and
      policy makers considering this methodological approach and suggest that with
      sufficient preparation and planning CRTs can be an acceptable and efficient
      methodology for studying the comparative effectiveness of therapeutics in real
      world settings.

PMID- 19402032
TI  - Psychotropic drug use in the Norwegian general population in 2005: data from the
      Norwegian Prescription Database.
AB  - PURPOSE: To analyse psychotropic drug utilisation patterns in the general
      population of Norway in 2005. METHODS: Data on 4,163,045 prescriptions of
      psychotropic drugs dispensed at all pharmacies in Norway during 2005 were
      extracted from The Norwegian Prescription Database (NorPD), including
      antipsychotics (ATC-code N05A), anxiolytics (N05B), hypnotics (N05C) and
      antidepressants (N06A). This information was merged with data concerning the 3857
      general practitioners (GPs) from the Norwegian Regular GP Scheme. RESULTS: A
      total of 705,230 individuals, or 15.3% of the general population, received at
      least one prescription of a psychotropic drug. The figures for the four
      therapeutic subgroups were 2.4% for antipsychotics, 6.2% for anxiolytics, 7.9%
      for hypnotics and 6.0% for antidepressants, respectively. For all subgroups,
      prevalence was higher among women than among men, and increased steadily by
      patients' age. The mean annual drug volume per patient was highest among persons
      aged 40-59 years, except for hypnotics where it continued to increase with age.
      GPs prescribed 80% of overall psychotropic drug volume, psychiatrists 5%, and
      other prescribers 15%. The proportion of the drugs issued by the three prescriber
      groups differed with the patients' age group. While children and adolescents
      received a relatively large share from paediatricians and child and adolescent
      psychiatrists, adults mostly got their prescriptions from GPs. CONCLUSIONS: The
      majority of psychotropic drugs were prescribed by GPs. Overall drug use increased
      significantly, and psychiatrists' contribution decreased significantly with
      patients' age. The quality of pharmacological treatment for mental health
      problems of the general and aging population therefore relies mainly on the GPs.

PMID- 19402031
TI  - Effects of highly active antiretroviral therapy (HAART) on cholesterol in HIV-1
      infected children: a retrospective cohort study.
AB  - OBJECTIVE: To determine the extent to which different highly active
      antiretroviral therapy (HAART) regimens pose risks for hypercholesterolemia in
      children with perinatal HIV-1. METHODS: A single center, retrospective cohort
      study examined different HAART regimens and total cholesterol (TC) levels. The
      primary outcomes were TC levels > 180, > 200 mg/dl. HAART was defined as multiple
      nucleoside analog reverse transcriptase inhibitors (NRTI), NRTI and protease
      inhibitor (PI) combinations (NRTI/PI), and NRTI and non-nucleoside analog reverse
      transcriptase inhibitor (NNRTI) combinations (NRTI/NNRTI). Controls were HIV-1
      infected children while on no medications (No MED). Univariate and multivariable
      Cox regression models generated hazard ratios for each of the primary outcomes
      with duration of therapy in the model. RESULTS: Of the 178 HIV-1 infected
      children eligible for study, 72.4% had TC > 180 mg/dl, 53.4% had TC > 200 mg/dl.
      For TC > 200, the multivariable analysis showed increased risk with NRTI/NNRTI
      (HR: 1.86, 95%CI: 1.34-2.19) and NRTI/PI (HR: 3.45, 95%CI: 2.65-4.51) when
      compared to No MED. Compared to NRTI/NNRTI, NRTI/PI increased the risk for TC >
      200 mg/dl (HR: 1.86, 95%CI: 1.45-2.39) in the multivariable model. CONCLUSIONS:
      In vertically acquired HIV-1 infected children, HAART elevates the risk of
      hypercholesterolemia. NRTI/PI increased risk of TC levels threefold, while
      NRTI/NNRTI increased risk twofold over No MED.

PMID- 19402033
TI  - Early reproductive maturity among Pume foragers: Implications of a pooled energy
      model to fast life histories.
AB  - Life history theory places central importance on relationships between ontogeny,
      reproduction, and mortality. Fast human life histories have been theoretically
      and empirically associated with high mortality regimes. This relationship,
      however, poses an unanswered question about energy allocation. In
      epidemiologically stressful environments, a greater proportion of energy is
      allocated to immune function. If growth and maintenance are competing energetic
      expenditures, less energy should be available for growth, and the mechanism to
      sustain rapid maturation remains unclear. The human pattern of extended juvenile
      provisioning and resource sharing may provide an important source of variation in
      energy availability not predicted by tradeoff models that assume independence at
      weaning. We consider a group of South American foragers to evaluate the effects
      that pooled energy budgets may have on early reproduction. Despite growing up in
      an environment with distinct seasonal under-nutrition, harsh epidemiological
      conditions, and no health care, Pume girls mature quickly and initiate
      childbearing in their midteens. Pooled energy budgets compensate for the low
      productivity of girls not only through direct food transfers but importantly by
      reducing energy they would otherwise expend in foraging activities to meet
      metabolic requirements. We suggest that pooled energy budgets affect energy
      availability at both extrinsic and intrinsic levels. Because energy budgets are
      pooled, Pume girls and young women are buffered from environmental downturns and
      can maximize energy allocated to growth completion and initiate reproduction
      earlier than a traditional bound-energy model would predict.

PMID- 19402034
TI  - The grandmaternal niche: Critical caretaking among Martu Aborigines.
AB  - This paper expands upon the existing literature on the evolutionary importance of
      grandmothers by examining how direct care by grandmothers differs from care
      provided by other helpers within a population of Martu Aborigines. Behavioral
      observations were collected on ten babies who ranged from 3 months to 3 years of
      age. The results show that Martu grandmothers were in contact with their
      grandchildren more than any person other than the mother, and they were also more
      likely than any other category of caregiver to perform high-demand tasks, such as
      bathing or feeding. These results suggest that Martu grandmothers are
      specializing in the type of care they provide and posits that high-quality
      allocare is an important pathway to increased health and survival of
      grandchildren.

PMID- 19402035
TI  - Seasonal modulation of reproductive effort during early pregnancy in humans.
AB  - Life history theory predicts that early pregnancy presents a relatively low cost,
      uncontested opportunity for a woman to terminate investment in a current
      reproductive opportunity if a conceptus is of poor quality and/or maternal status
      or environmental conditions are not propitious for a successful birth. We tested
      this hypothesis in rural Bolivian women experiencing substantial seasonal
      variation in workload and food resources. Significant risk factors for early
      pregnancy loss (EPL) included agropastoralism versus other economic strategies,
      conception during the most arduous seasons versus other seasons, and increasing
      maternal age. Anovulation rate (AR) was higher during the most arduous seasons
      and in older women. Breastfeeding and indicators of social status and living
      conditions did not significantly influence either risk of EPL or AR. Averaged
      over the year, anovulation occurred in about 1/4 of the cycles and EPL occurred
      in about 1/3 of the conceptions. This is the first evidence of seasonality of EPL
      in a non-industrialized population, and the first to demonstrate a relationship
      between economic activities and EPL. These findings suggest that both anovulation
      and EPL are potential mechanisms for modulating reproductive effort; such
      "failures" may also be nonadaptive consequences of conditions hostile to a
      successful pregnancy. In either case, variation in EPL risk associated with
      different subsistence activities can be expected to influence fertility levels
      and birth seasonality in both contemporary and past human populations. These
      consequences of variability in the risk of EPL can impact efforts to understand
      the sources of variation in reproductive success.

PMID- 19402036
TI  - Fertility, body size, and shape: An empirical test of the covert maternal
      depletion hypothesis.
AB  - In populations with limited resources, high-reproductive effort may lead to poor
      nutritional status of the mother (the maternal depletion syndrome), whereas in
      well-nourished populations woman's body weight tends to increase after each
      pregnancy. However, in affluent populations, women's body shape may change due to
      mobilization of polyunsaturated fatty acids (PUFAs) from the lower parts of their
      bodies to meet the needs of the developing child (the "covert maternal
      depletion"). We studied relationships between reproductive history traits and
      body size and shape for 296 rural, parous women in good nutritional status (mean
      body mass index, BMI = 27.9, SD = 5.94), aged 22-85 (mean 47.8, SD = 16.34) from
      southern Poland. Body mass adjusted for age, age of menarche, body height, and
      similarly adjusted BMI were each positively related to the number of children
      born by a woman (R = 0.13, P = 0.02 and R = 0.13, P = 0.02, respectively). Waist
      and hip circumferences, adjusted for confounders, did not show statistically
      significant relationships with the number of children. Moreover, groups with low
      and high parity did not significantly differ in hip/BMI and waist/BMI ratios,
      which were proposed to be indicators of covert form of maternal depletion (after
      controlling for overall body fatness and age). In conclusion, parity caused a
      slightly higher body mass and BMI later in life. However, parity did not lead to
      covert maternal depletion, perhaps because women in this population have
      relatively high-dietary intake of PUFAs.

PMID- 19402037
TI  - Endocrine mechanisms of primate life history trade-offs: growth and reproductive
      maturation in vervet monkeys.
AB  - Life history theory predicts that the timing of maturation will result from a
      trade-off between growth and the age of first reproduction. This trade-off and
      its mechanisms of action are still poorly understood in many species and have not
      been well studied at the individual level. This study examined hypothesized trade
      offs between growth and reproductive maturation in wild populations of vervet
      monkeys (Cercopithecus aethiops) from Kenya, East Africa. Individuals were
      sampled from four populations in widely separated sites differing in temperature,
      altitude, and rainfall. Biological samples and morphometric measures were
      collected from 50 adult males, 83 adult females, and 225 juveniles. Gonadal
      steroids and leptin levels were analyzed by radioimmunoassay of sera from 136
      juvenile males and 90 juvenile females. Cross-sectional profiles of morphometric
      and endocrine data were used to assess the onset and cessation of growth in
      relation to sexual maturation. Gonadal steroids were used to assess sexual
      maturation and breeding onset. Leptin was used as an index of nutritional state.
      Estimates of mortality were derived from population age-structure. Across
      populations, higher resource productivity and nutrient status were associated
      with more rapid growth. Shorter growth duration was associated with earlier
      reproductive onset. These findings provide support for models of trade-offs
      between the timing of growth completion and reproductive onset, but they are
      contradicted by the evidence that reproduction precedes the cessation of growth
      in these populations. The biphasic actions of estradiol provide an alternative
      model and mechanism for the growth-reproduction trade-off.

PMID- 19402039
TI  - Immediate- and delayed-type allergic reactions to amide local anesthetics:
      clinical features and skin testing.
AB  - PURPOSE: Amide type local anesthetic agents are among the most commonly used
      drugs in medicine. Several adverse drug reactions (ADRs) have been previously
      described with their use. Among them, allergic reactions are considered rare. The
      aim of this study was to describe the main characteristics of ADRs induced by
      amide type local anesthetic drugs. METHODS: We studied reports recorded in the
      French Pharmacovigilance database and the GERAP database over a 12-year period
      (1995-2006). For each report, we detailed the clinical features and skin tests
      used. Delayed or immediate-type allergic reactions and cross-reactivity between
      amide type local anesthetics were also analyzed. RESULTS: We identified 16
      reports (seven from the Pharmacovigilance database and nine from the GERAP
      database). Local anesthetic allergic reactions occurred mostly in young females
      (F/M sex ratio = 14:2). An immediate-type allergic reaction was encountered in
      11/16 cases. Lidocaine was the local anesthetic most often involved (11/16).
      Prick test, intradermal reaction, and challenge tests were used to confirm the
      diagnosis. A cross-reactivity between the different amide type local anesthetics
      was found in six cases (lidocaine-mepivacaine in all cases). CONCLUSIONS: This is
      the largest series of immediate-type local anesthetic allergic reactions reported
      in the literature. Cutaneous symptoms are the main features even though more
      serious symptoms may occur. Intradermal reaction and challenge tests are very
      helpful. Because cross-reactivity is not scarce, skin tests should involve
      several local anesthetics.

PMID- 19402038
TI  - Influence of helminth infections on childhood nutritional status in lowland
      Bolivia.
AB  - Infectious disease, such as diarrheal disease, respiratory infections, and
      parasitic infections, are an important source of nutritional and energetic stress
      in many populations. Inspired by the research and methodological innovations of
      A. Roberto Frisancho, this work considers the impact of childhood environment and
      local disease ecology on child health and nutritional patterns among an
      indigenous group in lowland Bolivia. Specifically, we examine the association
      between soil-transmitted helminth infection, especially hookworm species, and
      anthropometric markers of short- and long-term nutritional status. Fecal samples,
      anthropometric dimensions, and health interviews were collected for 92 children
      ranging in age from 2.0 to 10.9 years. Microscopic examination revealed high
      levels of parasitic infection, with 76% of children positive for hookworm species
      infections (77% of girls and 74% of boys). Less common infections included
      Ascaris lumbricoides, Trichurius trichiura, and Strongyloides stercoralis with
      only 15% of children positive for multiple-species infections. After adjusting
      for sex and age, no statistically significant associations were observed between
      helminth infections and the frequency of reported illness or anthropometric
      measures of nutritional status. These data demonstrate the difficulty of
      assessing nutritional impacts of endemic infections.

PMID- 19402041
TI  - Mass spectrometry-based absolute quantification of microsomal cytochrome P450 2D6
      in human liver.
AB  - We describe the assay of the human cytochrome P450 2D6 in a set of 30 genotyped
      liver samples using the 'absolute quantification' (AQUA) technique. We found
      approximately 30 fmol CYP2D6 per microg of microsomal protein, with the values
      spanning from 0 to nearly 80 fmol/microg. This is greater by a factor of 5-10
      from the compared to the currently accepted value, which was around 5
      fmol/microg. Our results thus suggest that the amount of cytochrome P450 (CYP)
      enzymes in liver have to be reassessed. We used quantitative Western blotting,
      calibration standards and activity assays, to validate the results. Our results
      show, that using the AQUA technique a true assay of CYP2D6 in human liver was
      possible.

PMID- 19402042
TI  - RSLpred: an integrative system for predicting subcellular localization of rice
      proteins combining compositional and evolutionary information.
AB  - The attainment of complete map-based sequence for rice (Oryza sativa) is clearly
      a major milestone for the research community. Identifying the localization of
      encoded proteins is the key to understanding their functional characteristics and
      facilitating their purification. Our proposed method, RSLpred, is an effort in
      this direction for genome-scale subcellular prediction of encoded rice proteins.
      First, the support vector machine (SVM)-based modules have been developed using
      traditional amino acid-, dipeptide- (i+1) and four parts-amino acid composition
      and achieved an overall accuracy of 81.43, 80.88 and 81.10%, respectively.
      Secondly, a similarity search-based module has been developed using position
      specific iterated-basic local alignment search tool and achieved 68.35% accuracy.
      Another module developed using evolutionary information of a protein sequence
      extracted from position-specific scoring matrix achieved an accuracy of 87.10%.
      In this study, a large number of modules have been developed using various
      encoding schemes like higher-order dipeptide composition, N- and C-terminal,
      splitted amino acid composition and the hybrid information. In order to benchmark
      RSLpred, it was tested on an independent set of rice proteins where it
      outperformed widely used prediction methods such as TargetP, Wolf-PSORT, PA-SUB,
      Plant-Ploc and ESLpred. To assist the plant research community, an online web
      tool 'RSLpred' has been developed for subcellular prediction of query rice
      proteins, which is freely accessible at http://www.imtech.res.in/raghava/rslpred.

PMID- 19402043
TI  - The cell wall and secretory proteome of a tobacco cell line synthesising
      secondary wall.
AB  - The utility of plant secondary cell wall biomass for industrial and biofuel
      purposes depends upon improving cellulose amount, availability and
      extractability. The possibility of engineering such biomass requires much more
      knowledge of the genes and proteins involved in the synthesis, modification and
      assembly of cellulose, lignin and xylans. Proteomic data are essential to aid
      gene annotation and understanding of polymer biosynthesis. Comparative proteomes
      were determined for secondary walls of stem xylem and transgenic xylogenic cells
      of tobacco and detected peroxidase, cellulase, chitinase, pectinesterase and a
      number of defence/cell death related proteins, but not marker proteins of primary
      walls such as xyloglucan endotransglycosidase and expansins. Only the
      corresponding detergent soluble proteome of secretory microsomes from the
      xylogenic cultured cells, subjected to ion-exchange chromatography, could be
      determined accurately since, xylem-specific membrane yields were of poor quality
      from stem tissue. Among the 109 proteins analysed, many of the protein markers of
      the ER such as BiP, HSP70, calreticulin and calnexin were identified, together
      with some of the biosynthetic enzymes and associated polypeptides involved in
      polymer synthesis. However 53% of these endomembrane proteins failed
      identification despite the use of two different MS methods, leaving considerable
      possibilities for future identification of novel proteins involved in secondary
      wall polymer synthesis once full genomic data are available.

PMID- 19402044
TI  - Proteome analysis of adipocyte lipid rafts reveals that gC1qR plays essential
      roles in adipogenesis and insulin signal transduction.
AB  - Since insulin receptors and their downstream signaling molecules are organized in
      lipid rafts, proteomic analysis of adipocyte lipid rafts may provide new insights
      into the function of lipid rafts in adipogenesis and insulin signaling. To search
      for proteins involved in adipocyte differentiation and insulin signaling, we
      analyzed detergent-resistant lipid raft proteins from 3T3-L1 preadipocytes and
      adipocytes by 2-DE. Eleven raft proteins were identified from adipocytes. One of
      the adipocyte-specific proteins was globular C1q receptor (gC1qR), an acidic 32
      kDa protein known as the receptor for the globular domain of complement C1q. The
      targeting of gC1qR into lipid rafts was significantly increased during
      adipogenesis, as determined by immunoblotting and immunofluorescence. Since the
      silencing of gC1qR by small RNA interference abolished adipogenesis and blocked
      insulin-induced activation of insulin receptor, insulin receptor substrate-1 (IRS
      1), Akt, and Erk1/2, we can conclude that gC1qR is an essential molecule involved
      in adipogenesis and insulin signaling.

PMID- 19402045
TI  - The secreted salivary proteome of the pea aphid Acyrthosiphon pisum characterised
      by mass spectrometry.
AB  - Nine proteins secreted in the saliva of the pea aphid Acyrthosiphon pisum were
      identified by a proteomics approach using GE-LC-MS/MS and LC-MS/MS, with
      reference to EST and genomic sequence data for A. pisum. Four proteins were
      identified by their sequences: a homolog of angiotensin-converting enzyme (an M2
      metalloprotease), an M1 zinc-dependant metalloprotease, a glucose-methanol
      choline (GMC)-oxidoreductase and a homolog to regucalcin (also known as
      senescence marker protein 30). The other five proteins are not homologous to any
      previously described sequence and included an abundant salivary protein
      (represented by ACYPI009881), with a predicted length of 1161 amino acids and
      high serine, tyrosine and cysteine content. A. pisum feeds on plant phloem sap
      and the metalloproteases and regucalcin (a putative calcium-binding protein) are
      predicted determinants of sustained feeding, by inactivation of plant protein
      defences and inhibition of calcium-mediated occlusion of phloem sieve elements,
      respectively. The amino acid composition of ACYPI009881 suggests a role in the
      aphid salivary sheath that protects the aphid mouthparts from plant defences, and
      the oxidoreductase may promote gelling of the sheath protein or mediate oxidative
      detoxification of plant allelochemicals. Further salivary proteins are expected
      to be identified as more sensitive MS technologies are developed.

PMID- 19402047
TI  - Proteomic analysis of the development and germination of date palm (Phoenix
      dactylifera L.) zygotic embryos.
AB  - By using a comparative proteomic approach (2-DE coupled to MS/MS), the
      development, maturation, and germination of date palm zygotic embryos, have been
      studied. Proteins were trichloroacetic acid (TCA)-acetone-phenol extracted and
      resolved by 2-DE in the 5-8 pH range. The total protein content and the number of
      spots resolved increased from early (12 weeks after pollination (WAP); 68.96 mg/g
      DW: 207 spots) to late (17 WAP; 240.85 mg/g DW: 261 spots) stages, decreasing
      upon germination (from 120.8 mg/g DW: 273 spots in mature embryos to 26.35 mg/g
      DW: 87 spots in 15 days after germination). Up to 194 spots showed qualitative or
      quantitative differences between stages. Statistical analysis of spot variation
      was performed by PCA, obtaining a more accurate grouping of the samples and
      determining the most discriminant spots. Samples were also clustered based on
      Pearson distance and Ward's minimum distance. Sixty-five variable spots were
      subjected to MS analysis, resulting in 21 identifications. The identified
      proteins belong to the following functional categories: enzymes of glycolysis,
      tricarboxylic acid cycle, and carbohydrate biosynthesis, protein translation,
      storage (glutelin), and stress-related proteins. The evolution pattern of the
      functional groups was examined and discussed in terms of metabolism adaptation to
      the different embryogenic and germination stages.

PMID- 19402046
TI  - Diabetic dyslipidemia and exercise alter the plasma low-density lipoproteome in
      Yucatan pigs.
AB  - Although low-density lipoprotein (LDL) plays a predominant role in atherogenesis,
      the low-density lipoproteome has not been fully characterized. Moreover,
      alterations from a Western diet, diabetes, and physical inactivity on this
      proteome have yet to be determined. Accordingly, relative quantification was
      determined in LDL proteins from male Yucatan diabetic dyslipidemic (DD) swine in
      the early stages of atherosclerosis compared to healthy control (C) and non
      diabetic hyperlipidemic (H) swine. Importantly, coronary vascular dysfunction was
      prevented by aerobic exercise training in these animals (DDX) without altering
      total LDL concentration. Using 2-DE, Western blot, label-free quantitative MS,
      and selected reaction monitoring, alterations in the abundance of apolipoproteins
      A-I, B, C-III, D, E, and J and noncovalently associated proteins were determined
      in LDL isolated using fast protein liquid chromatography. At least 28 unique
      proteins, many of which were novel, were identified with high confidence. An
      apolipoprotein E isoform demonstrated stronger correlation to disease (percent of
      coronary artery segments with intimal thickening) than some traditional risk
      factors (total cholesterol, LDL cholesterol, and LDL/HDL cholesterol). Taken
      together, this work identifies new possible biomarkers, potential therapeutic
      targets for atherosclerosis, and generates new hypotheses regarding the role of
      LDL in atherogenesis.

PMID- 19402048
TI  - Ductal adenocarcinoma of the prostate: clinical features and implications after
      local therapy.
AB  - BACKGROUND: Ductal or endometrioid adenocarcinoma of the prostate may be a
      subtype of prostate cancer that is amenable to aggressive local therapeutic
      strategies. The authors of this report investigated the clinical outcome of
      patients who had prostate ductal adenocarcinoma after primary radical
      prostatectomy or radiotherapy. METHODS: The clinical features of 108 patients
      with locally confined or advanced prostate ductal adenocarcinoma who had
      undergone primary radical prostatectomy (surgical group, n = 76 men) or no
      surgery (nonsurgical group, n = 32 men) were evaluated retrospectively. Clinical
      records were reviewed, and Gleason scores, clinical/pathologic stages, and
      preoperative prostate-specific antigen levels were examined. The clinical
      features that were assessed included local recurrence, distant metastasis, and
      progression-free and overall survival after primary therapy. RESULTS: In the
      surgical group, patients who had pure ductal prostate cancer survived longer
      (median, 13.8 years; 95% confidence interval [CI], from 13.8 years to not
      attained) than patients who had mixed ductal prostate cancer (median, 8.9 years;
      95% CI, from 7.1 years to not attained; P = .05). In addition, the median time to
      local progression was shorter (2.8 years vs 4.9 years) and the median time to
      distant metastasis was longer (3.9 years vs 2.0 years) for patients who had pure
      ductal adenocarcinoma than for patients who had mixed ductal adenocarcinoma of
      the prostate after surgery, respectively. CONCLUSIONS: The results of this
      preliminary study suggested that pure ductal prostate adenocarcinoma tends to
      pursue an indolent clinical course and poses an increased risk for local
      recurrence. Local control (particularly prostatectomy) may improve the clinical
      outcome of patients with pure prostate ductal adenocarcinoma. These results need
      to be confirmed in prospective studies.

PMID- 19402049
TI  - Change in health-related quality of life of newly diagnosed cancer patients,
      cancer survivors, and controls.
AB  - BACKGROUND: Data from the 1998 Health Outcomes Survey (HOS) of patients who were
      enrolled in Medicare managed care and follow-up data from the 2000 HOS resurvey
      were analyzed to examine changes in health-related quality of life (HRQOL) of
      newly diagnosed cancer patients, cancer survivors, and patients without cancer.
      METHODS: In 1998, the HOS was mailed to a random sample of 279,135 beneficiaries,
      and 167,096 respondents (60%) returned completed surveys. Those who were
      diagnosed with cancer (22,747) were frequency age-matched to an equal number of
      patients with no cancer. In 2000, the HOS was mailed to the same cohort of
      beneficiaries. Complete data at both baseline and follow-up were available on
      16,850 individuals for inclusion in the current study. RESULTS: After 2 years,
      respondents who had been diagnosed with cancer at baseline continued to have
      lower scores on all but 3 scales of the 36-item short-form HRQOL measure.
      However, there was no evidence that they were declining any faster than or
      catching up with noncancer patients. Those who had been newly diagnosed with
      cancer since the baseline survey had lower mean scale scores than the no-cancer
      group on all scales and lower mean scores than the cancer survivors on all
      subscales except Bodily Pain, Vitality, and Mental Health. CONCLUSIONS: This
      study demonstrated that, after 2 years, cancer survivors continued to have poorer
      HRQOL than the no-cancer group. Newly diagnosed cancer patients had poorer
      quality of life than both the longer term cancer survivors and the no-cancer
      group.

PMID- 19402050
TI  - High-dose chemotherapy and autologous hematopoietic progenitor cell rescue in
      children with recurrent medulloblastoma and supratentorial primitive
      neuroectodermal tumors: the impact of prior radiotherapy on outcome.
AB  - BACKGROUND: The role of myeloablative chemotherapy in children with recurrent
      medulloblastoma and supratentorial primitive neuroectodermal tumors (MB/ST-PNET)
      is controversial, in particular in patients who develop recurrent disease after
      craniospinal radiotherapy. METHODS: In this retrospective analysis, the authors
      investigated the outcome of children with recurrent MB/ST-PNET who were referred
      for myeloablative chemotherapy and autologous hematopoietic progenitor cell
      rescue at Childrens Hospital Los Angeles. RESULTS: Thirty-three children were
      referred for myeloablative chemotherapy: Fourteen of those children were never
      transplanted because of pre-transplant adverse events, and 19, including 6
      without and 13 with previous irradiation, underwent transplant. Conditioning
      regimens included a backbone of thiotepa, which was given either in a single
      cycle or in multiple sequential cycles. The 3-year post-transplant event-free
      survival rate in unirradiated versus previously irradiated children was 83% +/-
      15% versus 20% +/- 12%, respectively (P = .04). One child who had never been
      exposed to radiotherapy died of toxicity; the other children received post
      transplant radiotherapy and remained disease free. Nine previously irradiated
      children experienced 4 toxic deaths and 6 tumor recurrences (1 patient had both):
      An interval of <1 year between initial radiotherapy and myeloablative
      chemotherapy predicted a greater risk of toxic death (P = .02), whereas a history
      of meningeal metastases at diagnosis and a poor response to the initial rescue
      therapy predicted a greater risk of post-transplant recurrence (P = .03 and P =
      .08, respectively). CONCLUSIONS: Myeloablative doses of thiotepa-based
      chemotherapy and radiotherapy were able to cure most children who had
      radiotherapy-naive, chemoresponsive recurrences. Children who developed
      recurrences after craniospinal radiotherapy had poorer outcomes; however, cure
      was possible in those who had good prognostic features at presentation,
      chemoresponsive recurrences, and a long interval between initial radiotherapy and
      myeloablative chemotherapy.

PMID- 19402051
TI  - Derivatives of pyrazinecarboxylic acid: 1H, 13C and 15N NMR spectroscopic
      investigations.
AB  - NMR spectroscopic studies are undertaken with derivatives of 2-pyrazinecarboxylic
      acid. Complete and unambiguous assignment of chemical shifts ((1)H, (13)C, (15)N)
      and coupling constants ((1)H,(1)H; (13)C,(1)H; (15)N,(1)H) is achieved by
      combined application of various 1D and 2D NMR spectroscopic techniques.
      Unequivocal mapping of (13)C,(1)H spin coupling constants is accomplished by 2D
      (delta,J) long-range INEPT spectra with selective excitation. Phenomena such as
      the tautomerism of 3-hydroxy-2-pyrazinecarboxylic acid are discussed.

PMID- 19402052
TI  - Optimized port placement for in vivo biosensors.
AB  - BACKGROUND: We discuss the implementation of an automated port placement system
      for use with laparoscopic in vivo biosensors. Biosensors have physical
      limitations that make port placement crucial to proper data collection. The port
      placement process is prohibitively complex to execute optimally by human
      estimation. METHODS: Port placement algorithms were integrated into an image
      guided surgery system. Variables for optimization of ports include biosensor
      length, data collection restrictions, obstacles, and regions of interest. The
      port placement is applied to 3D virtual 'patients' created from medical imaging
      data. An example implementation for a Raman biosensor probe was created. RESULTS:
      The prototype system can correctly find ideal port locations on a virtual patient
      based on biosensor limitations and regions of interest. Conversely, the system
      can evaluate and score an individual port selected by a user. CONCLUSION: As
      biosensors become incorporated into laparoscopic surgical environments, an
      automated port placement system would enable their optimized integration.

PMID- 19402053
TI  - Brief guidance document on the appropriate use of human papillomavirus testing
      issued by the Cytology Education and Technology Consortium.

PMID- 19402054
TI  - Most states receive failing grade for tobacco control.

PMID- 19402056
TI  - Treatment of kidney cancer: insights provided by the VHL tumor-suppressor
      protein.
AB  - Germline inactivation of the VHL tumor suppressor gene is associated with an
      increased risk of clear cell carcinoma of the kidney in the context of von Hippel
      Lindau (VHL) disease. Somatic VHL mutations are also common in nonhereditary
      (sporadic) clear cell carcinomas. The VHL protein (pVHL) has multiple functions
      that might be linked to tumor suppression, including targeting the hypoxia
      inducible factor (HIF) transcription factor for polyubiquitylation and
      proteasomal degradation. HIF, especially HIF2alpha, appears to play a causal role
      in clear cell renal carcinogenesis based on genotype-phenotype correlations in
      VHL disease, laboratory experiments with human VHL-/- renal carcinoma cell lines,
      and genetically engineered mouse models. Deregulation of HIF almost certainly
      accounts for the high levels of vascular endothelial growth factor (VEGF)
      observed in kidney cancer and relates to their sensitivity to VEGF inhibitors. In
      addition, the beneficial effects of mammalian target of rapamycin (mTOR)
      inhibitors are likely due to, at least partly, their ability to down-regulate
      HIF. pVHL, in a HIF-independent manner, also regulates a specialized structure
      called the primary cilium and regulates apoptosis via factors such as NFkappaB.
      Loss of the primary cilium probably facilitates the development of preneoplastic
      renal cysts, whereas increased NFkappaB might contribute to the resistance of
      kidney cancers to conventional cytotoxic agents.

PMID- 19402055
TI  - Pioglitazone: more than just an insulin sensitizer.

PMID- 19402057
TI  - Tissue biomarkers in renal cell carcinoma: issues and solutions.
AB  - Renal cell carcinoma (RCC) is an aggressive malignancy that is associated with a
      high rate of metastasis. Although several promising therapeutic strategies are
      now available for the treatment of patients with metastatic kidney cancer, the
      prognosis of these patients remains poor. Research is ongoing to identify RCC
      specific biomarkers that can improve early diagnosis, surveillance of tumor
      progression, and prediction of patient prognosis. The identification of
      biomarkers that may predict response to specific therapies also will be useful in
      stratifying patients with RCC for treatment selection. Unfortunately, biomarker
      detection and measurement in kidney tumor tissues can be biased significantly by
      the lack of standardization in tissue sample acquisition, storage, and analysis.
      Consequently, the establishment of standardized operating procedures is necessary
      to maximize the accuracy of tissue-based biomarker assays. Herein, the authors
      discuss current issues in tissue-based translational research aimed at
      identifying clinically useful biomarkers for kidney cancer.

PMID- 19402058
TI  - Combination targeted therapy in advanced renal cell carcinoma.
AB  - Several novel therapies have been approved recently in advanced renal cell
      carcinoma (RCC). These agents inhibit pathways downstream of loss of the von
      Hippel-Lindau gene VHL. They target the vascular endothelial growth factor (VEGF)
      ligand, VEGF receptor (VEGFR), mammalian target of rapamycin (mTOR), and other
      potentially important pathways. Even with improvements in survival, disease
      progresses in all patients. There is a critical need to increase complete
      responses (now rare). One such strategy is combining several agents to block
      different levels of the VEGF-VEGFR axis (vertical blockade). Alternatively,
      combination of a VEGF-VEGFR inhibitor with an mTOR inhibitor is attractive.
      Finally, horizontal blockade of VEGFR with epidermal growth factor receptor
      and/or platelet-derived growth factor receptor, all signaling pathways activated
      by hypoxia-inducible factor, is another approach. Already trials have revealed
      difficulties with combination therapy. By combining agents, the toxicity of 1 or
      both can be enhanced. The authors of this article report their experience with
      sorafenib plus bevacizumab, which produced increases in hand-foot syndrome,
      hypertension, and proteinuria, all known toxic effects. Clinical activity was
      impressive with 25 responses in 48 patients (52% response rate). Other
      combinations also required dose reductions (sorafenib with temsirolimus) or were
      intolerable (sunitinib with temsirolimus or sunitinib with bevacizumab).
      Unexpected toxicity characterized by microangiopathic hemolytic anemia occurred
      late in treatment with sunitinib and bevacizumab. Toxicity may be more severe in
      patients with RCC, who frequently have 1 kidney and poor renal function. Once
      tolerability for combination regimens has been established, it will be critical
      to design informative phase 2 trials and address the benefit of combination
      versus sequential therapy.

PMID- 19402059
TI  - Novel therapeutics for metastatic renal cell carcinoma.
AB  - The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically
      during the past few years. Sunitinib malate, sorafenib tosylate, bevacizumab with
      interferon alpha, temsirolimus, and everolimus have improved clinical outcomes in
      randomized phase 3 trials by inhibiting the vascular endothelial growth factor
      and related pathways. Combinations and sequences of these agents are being
      evaluated. Other novel agents are in clinical development, some of which target
      novel pathways not yet exploited as therapy for RCC. Recently reported and
      ongoing clinical trials will help further define the role of these agents as
      therapy for metastatic RCC.

PMID- 19402060
TI  - Immunotherapy of metastatic renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) evokes an immune response, which occasionally has
      resulted in spontaneous and dramatic remissions. In an attempt to reproduce or
      accentuate this response, various immunotherapeutic strategies have been studied.
      The most consistent antitumor activity has been reported with interferon-alpha
      (IFN-alpha) and interleukin-2 (IL-2). In recent years, randomized trials have
      suggested that high-dose, intravenous bolus IL-2 is superior in terms of response
      rate and possibly in terms of response quality to regimens that involve either
      low-dose IL-2 and IFN-alpha, intermediate- or low-dose IL-2 alone, or low-dose
      IFN-alpha alone. More significantly, investigations associated with those trials
      suggested that the potential exists for identifying predictors of response (or
      resistance) and limiting IL-2 therapy to those patients who hare most likely to
      benefit. Although the role of low-dose, single-agent cytokines is limited,
      combinations of cytokines with targeted therapy may have merit. Several studies,
      including 2 completed, large, phase 3 trials of interferon plus bevacizumab
      versus interferon alone, have demonstrated superior efficacy with the combination
      regimen compared with cytokine monotherapy and suggested the potential of an
      additive effect that requires further exploration. For patients who are unlikely
      to benefit from IL-2 or who are unable to receive it, the emergence "targeted
      immunotherapy" offers hope for improved clinical outcome. Improvements in patient
      selection, novel agents, and combination therapy will be required to optimize the
      benefits of immunotherapy in metastatic RCC as the list of effective therapies
      grows.

PMID- 19402061
TI  - Golgi protein 73 as a biomarker of hepatocellular cancer: development of a
      quantitative serum assay and expression studies in hepatic and extrahepatic
      malignancies.

PMID- 19402062
TI  - Nepetanal and nepetanoate: a new diterpene aldehyde and a benzene derivative
      ester from Nepeta juncea.
AB  - One new tricyclic clerodane type diterpene aldehyde nepetanal (1) and one new
      benzene derivative nepetanoate (2) have been isolated from a plant Nepeta juncea
      together with two known compounds oleanolic acid (3) and ursolic acid (4). The
      structures of the isolated compounds were elucidated by means of modern
      spectroscopic techniques and comparison with literature data.

PMID- 19402064
TI  - Innovations and challenges in renal cancer: summary statement from the Third
      Cambridge Conference.
AB  - The Third Cambridge Conference on Innovations and Challenges in Renal Cancer, a
      symposium held in Cambridge, Massachusetts, June 27-28, 2008, and chaired by
      Michael B. Atkins, was convened to discuss the current state of knowledge in the
      field, critique new data, stimulate communication among those involved in basic
      and clinical research, and offer recommendations for further study. Four main
      topics were discussed: genetics and molecular biology of renal cell cancer,
      staging and prognosis, systemic therapy, and correlative science and biomarkers
      in stage IV disease. The conference format combined brief presentations with
      extended periods of discussion. The conclusions and recommendations are
      summarized in this paper and presented in more detail in the individual papers
      that follow.

PMID- 19402063
TI  - Impact of pretransplant hyponatremia on outcome following liver transplantation.
AB  - Hyponatremia is associated with reduced survival in patients with cirrhosis
      awaiting orthotopic liver transplantation (OLT). However, data are sparse
      regarding the impact of hyponatremia on outcome following OLT. We investigated
      the effect of hyponatremia at the time of OLT on mortality and morbidity
      following the procedure. The study included 2,175 primary OLT recipients between
      1990 and 2000. Serum sodium concentrations obtained immediately prior to OLT were
      correlated with subsequent survival using proportional hazards analysis.
      Morbidity associated with hyponatremia was assessed, including length of
      hospitalization, length of intensive care unit (ICU) admission, and occurrence of
      central pontine myelinolysis (CPM). Out of 2,175 subjects, 1,495 (68.7%) had
      normal serum sodium (>135 mEq/L) at OLT, whereas mild hyponatremia (125-134
      mEq/L) was present in 615 (28.3%) and severe hyponatremia (<125 mEq/L) in 65
      (3.0%). Serum sodium had no impact on survival up to 90 days after OLT
      (multivariate hazard ratio = 1.00, P = 0.99). Patients with severe hyponatremia
      tended to have a longer stay in the ICU (median = 4.5 days) and hospital (17.0
      days) compared to normonatremic recipients (median ICU stay = 3.0 days, hospital
      stay = 14.0 days; P = 0.02 and 0.08, respectively). There were 10 subjects that
      developed CPM, with an overall incidence of 0.5%. Although infrequent, the
      incidence of CPM did correlate with serum sodium levels (P < 0.01). CONCLUSION:
      Pre-OLT serum sodium does not have a statistically significant impact on survival
      following OLT. The incidence of CPM correlates with hyponatremia, although its
      overall incidence is low. Incorporation of serum sodium in organ allocation may
      not adversely affect the overall post-OLT outcome.

PMID- 19402065
TI  - Prognostic factors for survival in metastatic renal cell carcinoma: update 2008.
AB  - A variety of prognostic factor models to predict survival in patients with
      metastatic renal cell carcinoma have been developed. Diverse populations of
      patients with variable treatments have been used for these analyses. A variety of
      clinical, pathologic, and molecular factors have been studied, but current models
      use predominantly easily obtained clinical factors. These approaches are
      reviewed, and current approaches to further refine and develop these techniques
      are reviewed.

PMID- 19402066
TI  - Neoadjuvant (presurgical) therapy for renal cell carcinoma: a new treatment
      paradigm for locally advanced and metastatic disease.
AB  - BACKGROUND: Although upfront cytoreductive nephrectomy followed by systemic
      therapy remains the standard of care for metastatic renal cell carcinoma, the
      addition of novel targeted therapy has prompted a reevaluation of this treatment
      paradigm. The authors reviewed their experience with neoadjuvant systemic therapy
      administered before cytoreductive surgery for metastatic, locally recurrent, or
      regionally advanced renal cell carcinoma. METHODS: The authors compared patients
      treated with presurgical targeted therapy (with sunitinib, sorafenib, or
      bevacizumab) with a contemporary group that underwent up-front cytoreductive
      surgery. RESULTS: The authors found no difference in any perioperative surgical
      parameters indicative of morbidity or mortality between the 2 groups. Laboratory
      models of renal cell carcinoma treated with systemic targeted therapy demonstrate
      specific protein expression profiles that correlate with response to therapy and
      the development of therapy resistance. CONCLUSIONS: Neoadjuvant (presurgical)
      targeted therapy before cytoreductive surgery appears safe in the setting of
      metastatic renal cell carcinoma. It identifies patients who respond to systemic
      therapy before surgery, thus avoiding highly morbid surgery in patients destined
      for a poor outcome. Further studies are needed to identify the molecular
      endpoints associated with treatment response and the development of the resistant
      phenotype, which will in turn identify novel transduction pathways worthy of
      therapeutic development.

PMID- 19402067
TI  - Sequential therapy in renal cell carcinoma.
AB  - Because of the recent approval of several drugs for the treatment of renal cell
      carcinoma (including sorafenib, sunitinib, temsirolimus, and, in Europe,
      bevacizumab plus interferon), the use of sequential therapy has become routine
      practice. There is now evidence that administering these targeted agents
      sequentially provides clinical benefit by inducing tumor shrinkage and prolonged
      progression-free survival (PFS) in a large number of patients. However, data
      regarding overall survival (OS) are still pending. By adding these drugs in an
      adequate order, one can expect an increase in overall PFS of up to 27 months and
      a subsequent improvement in the OS of patients with renal cell carcinoma. It has
      been recently reported that the OS of patients treated with sunitinib in the
      first-line setting was 26 months. Expecting a survival of 40 months does appear
      possible based on currently available data, although this assumption will have to
      be proven in the future.

PMID- 19402068
TI  - Functional correlates of fiber architecture of the lateral caudal musculature in
      prehensile and nonprehensile tails of the platyrrhini (primates) and procyonidae
      (carnivora).
AB  - Prehensile-tailed platyrrhines (atelines and Cebus) and procyonids (Potos)
      display bony tail features that have been functionally and adaptively linked to
      their prehensile behaviors, particularly the need to resist relatively greater
      bending and torsional stresses associated with supporting their body weight
      during suspensory postures. We compared fiber architecture of the mm.
      intertransversarii caudae (ITC), the prime tail lateral flexors/rotators, in 40
      individuals distributed across 8 platyrrhine and 2 procyonid genera, divided into
      one of two groups: prehensile or nonprehensile. We tested the hypothesis that
      prehensile-tailed taxa exhibit relatively greater physiologic cross-sectional
      areas (PCSAs) to maintain tail suspensory postures for extended periods. As an
      architectural trade-off of maximizing force, we also predicted prehensile-tailed
      taxa would exhibit relatively shorter, more pinnate fibers, and a lower mass to
      tetanic tension ratio (Mass/P(O)). Prehensile-tailed taxa have relatively higher
      PCSAs in all tail regions, indicating their capacity to generate relatively
      greater maximum muscle forces compared to nonprehensile-tailed taxa. Contrary to
      our predictions, there are no group differences in pinnation angles, fiber
      lengths or M/P(O) ratios. Therefore, the relatively greater prehensile PCSAs are
      driven largely by relative increase in muscle mass. These findings suggest that
      relatively greater ITC PCSAs can be functionally linked to the need for
      prehensile-tailed taxa to suspend and support their body weight during arboreal
      behaviors. Moreover, maximizing ITC force production may not come at the expense
      of muscle excursion/contraction velocity. One advantage of this architectural
      configuration is it facilitates suspension of the body while simultaneously
      maximizing tail contact with the substrate.

PMID- 19402070
TI  - Magnetic resonance imaging as a biomarker in renal cell carcinoma.
AB  - The ability to noninvasively discriminate the most common types of renal cell
      carcinoma (RCC) based on their magnetic resonance imaging (MRI) appearances or
      their magnetic resonance phenotypes is achievable. Intracellular lipids, a
      histologic characteristic of the clear cell RCC, can be identified on chemical
      shift MRI. Intratumoral hemosiderin deposition, as observed histologically with
      papillary RCC, correlates to the low signal intensity on T2-weighted images. In
      addition to morphologic imaging features, the different subtypes of RCC have
      distinct patterns of enhancement on dynamic contrast-enhanced MRI. Clear cell
      tumors demonstrate much greater enhancement than papillary and chromophobe RCCs
      during the corticomedullary and nephrographic phases. The MRI technique arterial
      spin labeling (ASL) uses magnetic fields to label the water protons in arterial
      blood and measures blood flow into tissue; quantitative images of blood flow can
      be generated without exogenous contrast media. Multiple measurements of tumor
      perfusion may be repeated before and after a physiologic or drug challenge (ie,
      antiangiogenic therapy). In RCC xenografts and in patients with metastatic RCC,
      ASL MRI assessments can be used to monitor blood flow changes in response to
      antiangiogenic therapies. High blood flow on ASL MRI in RCC xenografts correlates
      with viable tumor at histopathologic analysis, whereas zones of absent or
      diminished signal correspond to necrosis. ASL MRI has the potential to serve as a
      biomarker for patients with metastatic RCC by offering a noninvasive measure of
      tumor blood flow changes accompanying antiangiogenic therapy.

PMID- 19402069
TI  - Treatment selection for patients with metastatic renal cell carcinoma.
AB  - The availability of approved agents with distinct mechanisms of action has
      encouraged investigations to identify optimal treatment strategies for specific
      patients and specific tumor features. Study of tumors from patients treated with
      interleukin-2 (IL-2) has suggested that response was unlikely in patients with
      tumors with papillary features or low carbonic anhydrase IX (CAIX) expression. A
      model combining histologic features and CAIX expression separated patients into 2
      groups of roughly equal size, with 96% of the responding patients being in the
      favorable prognostic group. Additional studies have begun to identify molecular
      features that might predict response to IL-2 therapy. In contrast, clinical trial
      data suggest that temsirolimus was relatively more active than interferon in
      patients with tumors containing non-clear cell features. Furthermore, pathologic
      examination showed no correlation of response with CAIX expression, but an
      apparent association with high expression of either phospho-AKT or phospho-S6,
      proteins either upstream or downstream of mammalian target of rapamycin.
      Preliminary investigations of tumor specimens from patients receiving vascular
      endothelial growth factor-targeted therapy suggested that high hypoxia-inducible
      factor expression might predict response. In addition, response appeared more
      likely in tumors with mutated or methylated VHL genes; however, substantial
      antitumor activity was still observed in patients with VHL wild-type tumors,
      particularly in patients treated with either sunitinib or axitinib, rather than
      bevacizumab or sorafenib. Although these data provide some guidance in treatment
      selection, considerably more research is needed to identify and validate
      selection models for particular treatment approaches, and to enable rational and
      optimal utilization of the available treatment options.

PMID- 19402071
TI  - Complexity of tumor vasculature in clear cell renal cell carcinoma.
AB  - Clear cell renal cell carcinoma (CCRCC) is a highly vascularized cancer resistant
      to conventional chemotherapy and radiotherapy. Antiangiogenic therapy has
      achieved some effectiveness against this unique malignancy. The complexity of the
      tumor vasculature in CCRCC has led to differences in correlating tumor
      microvessel density with patient prognosis. The authors' recent findings
      demonstrated that there were at least 2 major categories of tumor vessels in
      CCRCC-namely, undifferentiated and differentiated-correlating with patient
      prognosis in contrasting ways, with higher undifferentiated vessel density
      indicating poorer prognosis, and higher differentiated vessel density correlating
      with better prognosis. Furthermore, the presence of pericytes supporting the
      differentiated vessels varied in CCRCC. The distributions of pericyte coverage
      and differentiated vessels in CCRCC were uneven. The tumor margin had a higher
      pericyte coverage rate for differentiated vessels than did the inner tumor area.
      The uneven distributions of pericyte coverage and differentiated vessels in CCRCC
      prompted the authors to revisit the mechanism of tumor central necrosis, which
      was also known to be a prognostic indicator for CCRCC. The discrepancy of
      prognostic correlation between protein and messenger RNA levels of vascular
      endothelial growth factor in CCRCC was discussed. The complexity of the tumor
      vasculature in CCRCC also led the authors to begin to re-evaluate the therapeutic
      effects of antiangiogenic agents for each type of tumor vessel, which will in
      turn significantly broaden understanding of tumor angiogenesis and improve
      therapeutic effect.

PMID- 19402072
TI  - Targeting mTOR in renal cell carcinoma.
AB  - The mammalian target of rapamycin (mTOR) is clearly an important therapeutic
      target for advanced renal cell carcinoma (RCC), although its mechanisms of
      activation are not completely understood. In first-line treatment of patients who
      have both advanced RCC and multiple risk factors for short survival, temsirolimus
      improves overall survival (OS) compared with interferon. In patients whose tumors
      have progressed after sunitinib and/or sorafenib therapy, everolimus improves
      progression-free survival compared with placebo. Beyond the initial phase 3
      studies demonstrating efficacy, many important questions remain in the clinical
      application of mTOR inhibition and in developing other inhibitors of
      PI3K/Akt/mTOR signaling. Important objectives of current and future clinical
      investigations include a more detailed description of the molecular pathology of
      RCC and identification of potential biomarkers that are predictive of tumor
      sensitivity to PI3K/Akt/mTOR targeted therapies. This information may identify
      other groups of RCC patients that are likely to benefit from inhibition of this
      signaling pathway. Additional questions concern mechanisms by which tumors become
      resistant to mTOR inhibitor therapy and how such resistance can be defeated.
      Possible mechanisms include the loss of feedback inhibition of insulin receptor
      substate/PI3K signaling resulting from the inhibition of mTOR complex 1 by
      rapamycin analogs and the activating phosphorylation of Akt by mTOR complex 2.
      Laboratory studies indicate that these resistance mechanisms could be countered
      by using other targeted agents in combination with mTOR inhibitors.

PMID- 19402073
TI  - Vascular endothelial growth factor-targeted therapy in metastatic renal cell
      carcinoma.
AB  - Inactivation of the von Hippel-Lindau tumor suppressor gene in most sporadic
      renal cell carcinoma (RCC) tumors leads to a fundamental reliance on elements of
      this pathway, namely, the potent proangiogenic factor, vascular endothelial
      growth factor (VEGF). Thus, VEGF-targeted therapeutics have undergone extensive
      clinical testing in RCC. Approaches to bind circulating VEGF protein (eg,
      bevacizumab) and small molecule inhibitors of the receptor on which the VEGF
      ligand binds (eg, sunitinib, sorafenib, axitinib, and pazopanib) have been
      tested. Robust clinical effects have been observed, including high objective
      response rates, prolonged progression-free survival, and evidence of long overall
      survival for patients with metastatic RCC patients who are treated with these
      agents. Future directions include investigation of combination and sequenced
      therapy, elucidation of mechanisms of response and resistance, and exploration of
      the effect of these agents in other disease settings.

PMID- 19402074
TI  - Circulating biomarkers for vascular endothelial growth factor inhibitors in renal
      cell carcinoma.
AB  - In recent years, there has been significant progress in the clinical development
      and application of antiangiogenic therapies in renal cell carcinomas,
      particularly inhibitors of the vascular endothelial growth factor (VEGF) pathway.
      Despite this progress, no validated methods are currently available for
      identifying which patients are most likely to respond to treatment or experience
      toxic effects, selecting the optimal dose, or determining whether the intended
      molecular target has been effectively inhibited. However, recent studies have
      suggested that some of the biomarkers currently under investigation in clear cell
      renal cell carcinoma for VEGF pathway inhibitors are promising. These biomarkers
      include circulating proangiogenic factors and receptors; markers of hypoxia and
      endothelial damage; and cellular populations in peripheral blood, such as
      circulating endothelial cells. Further preclinical and translational validation
      studies are still needed to determine their practical utility in the clinical
      setting.

PMID- 19402076
TI  - Ultrasound-derived fetal size nomogram for a sub-Saharan African population: a
      longitudinal study.
AB  - OBJECTIVES: To create a fetal size nomogram for use in sub-Saharan Africa and
      compare the derived centiles with reference intervals from developed countries.
      METHODS: Fetal biometric measurements were obtained at entry to antenatal care
      (11-22 weeks' gestation) and thereafter at 4-week intervals from pregnant women
      enrolled in a longitudinal ultrasound study in Kinshasa, Democratic Republic of
      Congo. The study population comprised 144 singleton gestations with ultrasound
      derived gestational age within 14 days of the menstrual estimate. A total of 755
      monthly ultrasound scans were included with a mean +/- SD of 5 +/- 1 (range, 2-8)
      scans per woman. Estimated fetal weight (EFW) was calculated at each ultrasound
      examination using the Hadlock algorithm. A general mixed-effects linear
      regression model that incorporated random effects for both the intercept and
      slope was fitted to log-transformed EFW to account for both mean growth and
      within-fetus variability in growth. Reference centiles (5(th), 10(th), 50(th),
      90(th) and 95(th) centiles) were derived from this model. RESULTS: Nomograms
      derived from developed populations consistently overestimated the 50(th) centile
      EFW value for Congolese fetuses by roughly 5-12%. Differences observed in the
      10(th) and 90(th) centiles were inconsistent between nomograms, but generally
      followed a pattern of overestimation that decreased with advancing gestational
      age. CONCLUSIONS: In low-resource settings, endemic malaria and maternal
      nutritional factors, including low prepregnancy weight and pregnancy weight gain,
      probably lead to lower fetal weight and utilization of nomograms derived from
      developed populations is not appropriate. This customized nomogram could provide
      more applicable reference intervals for diagnosis of intrauterine growth
      restriction in sub-Saharan African populations.

PMID- 19402075
TI  - Hereditary kidney cancer: unique opportunity for disease-based therapy.
AB  - Kidney cancer is not a single disease; it is comprised of several different types
      of cancer, each with a different histology, with a different clinical course,
      caused by a different gene, and responding differently to therapy. The VHL gene
      is the gene for the hereditary cancer syndrome, von Hippel-Lindau, as well as for
      the common form of sporadic, noninherited, clear cell kidney cancer.
      Understanding the VHL-hypoxia inducible factor (HIF) pathway has provided the
      foundation for the development of several agents targeting this pathway, such as
      sunitinib, sorafenib, and temsirolimus. Hereditary papillary renal carcinoma
      (HPRC) is a hereditary renal cancer syndrome in which affected individuals are at
      risk for the development of bilateral, multifocal, type 1 papillary renal cell
      carcinoma. The genetic defect underlying HPRC is MET, the cell surface receptor
      for hepatocyte growth factor. Mutations of MET also have been identified in a
      subset of tumors from patients with sporadic type 1 papillary renal cell
      carcinoma (RCC). Clinical trials targeting the MET pathway are currently underway
      in patients with HPRC and in patients with sporadic (nonhereditary) papillary
      kidney cancer. The BHD gene (also known as folliculin or FLCN) is the gene for
      Birt-Hogg-Dube syndrome, an autosomal-dominant genodermatosis associated with a
      hereditary form of chromophobe and oncocytic, hybrid RCC. Preclinical studies are
      underway targeting the BHD gene pathway in preparation for clinical trials in
      Birt-Hogg-Dube and sporadic chromophobe RCC. Patients with hereditary
      leiomyomatosis RCC (HLRCC) are at risk for developing cutaneous and uterine
      leiomyomas and a very aggressive type of RCC. HLRCC is characterized by germline
      mutation of the Krebs cycle enzyme, fumarate hydratase (FH). Studies of the
      tricarboxylic acid cycle and the VHL-HIF pathways have provided the foundation
      for therapeutic approaches in patients with HLRCC-associated kidney cancer as
      well as other hereditary and sporadic forms of RCC.

PMID- 19402077
TI  - Preoperative prediction of poorly differentiated components in small-sized
      hepatocellular carcinoma for safe local ablation therapy.
AB  - BACKGROUND: Poorly differentiated hepatocellular carcinoma (HCC) has a malignant
      potential such as frequent microvascular invasion even if the tumor is smaller
      than 3 cm in diameter. The aim of this study was to clarify the preoperative
      predictors of poorly differentiated HCC for safe local ablation therapy. METHODS:
      Sixty-six patients underwent a hepatic resection for solitary small-sized HCC
      (<or=3 cm) were included in this study. According to the postoperative
      histological examination, the patients were divided into a "poorly differentiated
      group" (n = 17) and a "well/moderately differentiated group" (n = 49). This study
      investigated the clinicopathological factors and imaging findings, and elucidated
      the predictive factors of the poorly differentiated type. RESULTS: In a
      univariate analysis, serum hepatitis B surface antigen positive, hepatitis C
      virus antibody negative, alpha-fetoprotein level, des-gamma-carboxy prothrombin
      level, and a high contrast-to-noise ratio (CNR) in T2-weighted MR imaging were
      significantly associated with the poorly differentiate type. In a multivariate
      analysis, a high CNR in T2-weighted MR imaging was the only independent predictor
      of the poorly differentiated type. In the postoperative pathological findings,
      portal vein invasion and intrahepatic metastasis were significantly frequent in
      the poorly differentiated group. CONCLUSIONS: The CNR in T2-weighted MR imaging
      is a useful tool to predict poorly differentiated HCC preoperatively.

PMID- 19402079
TI  - Long-term follow-up results of fertility sparing surgery in patients with
      epithelial ovarian cancer.
AB  - BACKGROUND AND OBJECTIVE: To assess clinical and obstetric outcome in young
      patients with epithelial ovarian cancer treated with fertility sparing surgery.
      METHODS: Eighteen patients younger than 40 years carrying epithelial ovarian
      tumors were submitted to fertility sparing surgery between 1988 and 2003. Disease
      free (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.
      Statistical analysis was performed with the chi(2) test. RESULTS: Disease free
      survival (DFS) 83.3% and overall survival (OS) 94.4% of patients treated with
      conservative surgery at 10 years. Up to date, six of seven patients who attempted
      pregnancy delivered seven healthy newborns. CONCLUSION: Conservative surgery in
      young women with epithelial ovarian cancer is an appropriate therapeutic option
      in patients who wish to preserve childbearing potential. Long-term follow-up
      results shows excellent overall survival and pregnancy results.

PMID- 19402078
TI  - To what extent are soil amendments useful to control Verticillium wilt?
AB  - The genus Verticillium includes several species that attack economically
      important crops throughout the world. The control of Verticillium spp. becomes
      especially difficult when they form microsclerotia that can survive in the field
      soil for several years. It has been common practice to fumigate soil with
      chemicals such as methyl bromide and/or chloropicrin to control soil-borne fungal
      pathogens. Other chemicals that are used against Verticillium spp. are the
      antifungal antibiotic aureofungin, the fungicides benomyl, captan, carbendazim,
      thiram, azoxystrobin and trifloxystrobin and the plant defence activator
      acibenzolar-S-methyl. However, the potential risks involved in applying
      phytochemicals to crop plants for both the environment and human health, together
      with their limited efficacy for controlling Verticillium-induced diseases,
      support the need to find alternatives to replace their use or improve their
      efficacy. Soil amendment with animal or plant organic debris is a cultural
      practice that has long been used to control Verticillium spp. However, today the
      organic farming industry is becoming a significant player in the global
      agricultural production scene. In this review, some of the main results
      concerning the efficacy of several soil amendments as plant protectors against
      Verticillium spp. are covered, and the limitations and future perspectives of
      such products are discussed in terms of the control of plant diseases.

PMID- 19402080
TI  - Expression of extracellular matrix molecules in brain metastasis.
AB  - BACKGROUND AND OBJECTIVES: The objectives of this study were to investigate the
      role of growth factors and matrix metalloproteinases in the brain metastasis.
      METHODS: Tumors from 40 patients with brain metastasis (30 lung cancer, 10 breast
      cancer) were studied to investigate the expression-patterns of EGFR, MT1-MMP,
      MMP7, and CD44 using the immunostaining and RT -PCR analysis. RESULTS: EGFR
      immunostaining was detected in 92% (23/25) and 70% (7/10) of brain metastasis
      from lung adenocarcinoma and breast cancer, respectively. MT1-MMP immunostaining
      was also detected in 80% (20/25) and 50% (5/10) of brain metastasis from lung
      adenocarcinoma and breast cancer, respectively. EGFR mRNA was detected in 83.3%
      (25/30) and 70% (7/10) of brain metastasis from lung cancer and breast cancer,
      respectively. MT1-MMP mRNA was detected in 73.3% (22/30) specimens of brain
      metastasis from lung cancer, and only 13.3% (4/30) specimens of these patients
      expressed MMP7 mRNA. CONCLUSIONS: The high expression of EGFR and MT1-MMP
      indicates that a extracellular matrix remodeling may be playing an important role
      in brain metastasis.

PMID- 19402081
TI  - Pathological analysis after neoadjuvant chemoradiotherapy for esophageal
      carcinoma: the Rotterdam experience.
AB  - Multimodality treatment is increasingly used in the treatment for esophageal
      cancer. We determined the tumor regression grade after preoperative
      chemoradiation and correlated the effect of specific pathologic and clinical
      findings to overall survival. For this purpose esophageal biopsies and surgical
      specimens of 67 patients treated with neoadjuvant paclitaxel and carboplatin
      concurrent with radiotherapy were reviewed. Neoadjuvant chemoradiotherapy led to
      a significant downstaging. Complete tumor regression was found in 24% of the
      patients resulting in a trend towards better survival. It was found more
      frequently in poorly differentiated tumors. Patients with pre-treatment nodal
      involvement, assessed by endoscopic ultrasound, had a significantly worse
      survival compared to patients without. Contrastingly, this was not found for post
      treatment nodal involvement, as determined by pathological examination,
      speculating that survival is more determined by (submicroscopic) distant disease,
      than by locoregional tumor cells.

PMID- 19402082
TI  - 9-Boraanthracene derivatives stabilized by N-heterocyclic carbenes.
AB  - 2009: A boraanthracene odyssey: General routes to boraanthracene derivatives-
      long proposed, but never observed--are disclosed, along with the structural and
      photophysical properties of these compounds and their remarkable reactivity
      towards oxygen.

PMID- 19402083
TI  - A bis(silaselenone) with two donor-stabilized Si=Se bonds from an unexpected
      stereoconvergent hydrolysis of a diselenadisiletane.
AB  - SiSe matters: Diselenadisiletane 2, formed from direct reaction of a racemic
      silylene 1 with elemental selenium, gives the first bis(silaselenone) upon
      hydrolysis with water (3; see picture, C gray, H white, N blue, O red, Se purple,
      Si green; d(Si=Se) = 215 pm). The reaction is stereoconvergent: only racemic
      forms of 3 are obtained from a mixture of racemic and meso forms of 2.

PMID- 19402084
TI  - Platinum(II)-catalyzed intramolecular cyclization of o-substituted aryl alkynes
      through sp3 C-H activation.
AB  - Ring leader: PtCl(2) catalyzes intramolecular cyclization of o-isopropyl or o
      benzyl aryl alkynes to give substituted indene derivatives with good yields and
      high selectivity. This reaction appears to proceed through an sp(3) C-H
      activation and 1,4-hydrogen migration pathway (see scheme).

PMID- 19402086
TI  - Toroidal micelles of uniform size from diblock copolymers.
AB  - Uniform nanodonuts: Stable toroidal micelles that have a highly uniform size and
      shape spontaneously self-assemble from a selective THF/ethanol solvent mixture
      (see 3D AFM image). The donut-shaped micelles can be used as a template to grow
      gold nanoparticles, which form along the ring surface.

PMID- 19402085
TI  - "On-off" multivalent recognition: degradable dendrons for temporary high-affinity
      DNA binding.
AB  - Now you bind it--now you don't! Chemical degradation of a dendritic scaffold
      allows multivalent interactions with DNA to be "switched off" as the multivalent
      array of ligands breaks down into smaller fragments, offering an approach by
      which a molecule can be temporarily endowed with high affinity for a biological
      target--an important concept in the development of new synthetic systems to
      intervene in biological pathways.

PMID- 19402087
TI  - A convenient method for the synthesis of alpha-ethynylphospholes and modulation
      of their pi-conjugated systems.
AB  - Mind the (narrow) gap: Alpha-ethynylphospholes generated in situ from the
      corresponding silyl-capped precursors were converted into a series of alpha
      (arylethynyl) phospholes bearing functional substituents as well as an
      alpha,alpha'-linked terphosphole (see scheme). The terphosphole has a narrow HOMO
      LUMO gap owing to efficient pi conjugation over the three phosphole rings.

PMID- 19402089
TI  - Synthesis of beta,gamma-unsaturated acids from allenes and carbon dioxide.
AB  - Hidden talent: Often perceived to be too thermodynamically and kinetically inert
      to be a useful chemical feedstock, carbon dioxide adds to allenes under
      exceptionally mild reductive conditions in the presence of a palladium pincer
      complex to give beta,gamma-unsaturated carboxylic acids (see scheme). This
      transformation is discussed in the context of the requirements for CO(2)
      fixation. DMF = N,N-dimethylformamide, Tf = trifluoromethanesulfonyl.

PMID- 19402088
TI  - Mechanical nanosensor based on FRET within a thermosome: damage-reporting
      polymeric materials.

PMID- 19402090
TI  - A chemical approach to immunoprotein engineering: chemoselective
      functionalization of thioester proteins in their native state.
AB  - Less than 6 feet under: Serum proteins C3, C4, and alpha(2)M each contain a
      thioester domain buried within a hydrophobic pocket, which is thought to shield
      the labile thioester from hydrolysis. Herein, we make use of the inherent
      reactivity of the hydrazide for thioester moieties to chemoselectively label
      these crucial serum regulators in their native conformation; this demonstrates
      that access to the thioester site is much greater than previously supposed.

PMID- 19402091
TI  - Controlling the formation of cyanine dye H- and J-aggregates with cucurbituril
      hosts in the presence of anionic polyelectrolytes.
AB  - The presence of anionic polyelectrolytes enhances the tendency of cationic
      cyanine dyes to form aggregates in aqueous media. In this work we investigate the
      interactions between two cyanine dyes, pseudoisocyanine (PIC) and pinacyanol
      (PIN), with polystyrenesulfonate (PSS) as the key additive to develop J- and H
      aggregates. We also take advantage of the binding properties of the
      cucurbit[7]uril (CB7) host to control formation of these aggregates through its
      host-guest interactions with the dye molecules. UV/Vis absorption spectroscopic
      studies clearly demonstrate the PSS-enhanced formation of J-aggregates in the
      case of PIC and H-aggregates in the case of PIN. Electrostatic interactions
      between the cyanine dye molecules and the polyelectrolyte chains assist the
      formation of J- or H-aggregates at very low dye concentrations (ca. 10 microM).
      Optimum development of dye aggregates was observed at a sulfonate/dye molar ratio
      of about 3:1. Departures from this stoichiometric ratio seem to perturb the
      optimal aggregate structure. Furthermore, the presence of CB7 was found to
      effectively disrupt the interactions responsible for dye aggregation. Thus, CB7
      completely disrupts the J-aggregates formed by PIC and the H-aggregates (as well
      as lower concentrations of J-aggregates) formed by PIN. UV/Vis and emission
      spectroscopic studies clearly indicate that binding of CB7 to both dye molecules
      removes them from the aggregate structures. Our spectroscopic data clearly
      indicate that regulation of the relative molar ratios of dye, CB7 host, and
      polyelectrolyte sulfonate groups leads to a quantitative control of dye
      aggregation, yielding variable amounts of PIC J- and PIN H-aggregates in these
      solutions.

PMID- 19402092
TI  - The laulimalide family: total synthesis and biological evaluation of
      neolaulimalide, isolaulimalide, laulimalide and a nonnatural analogue.
AB  - We herein describe in full detail the first total synthesis of the antitumor
      agents neolaulimalide and isolaulimalide as well as a highly efficient route to
      laulimalide. A Kulinkovich reaction followed by a cyclopropyl-allyl rearrangement
      is used to install the exo-methylene group. The C(2)-C(16) aldehyde fragment is
      coupled with the C(17)-C(28) sulfone fragments by a highly (E)-selective Julia
      Lythgoe-Kocienski olefination to deliver the key intermediates of all three
      syntheses. Various conditions for the Yamaguchi macrolactonization are applied to
      close the individual macrocycles. Finally a carefully elaborated endgame was
      developed to solve the problem of acyl migration in the case of neolaulimalide.
      All compounds were tested against several cell lines. The cytotoxicity of
      neolaulimalide could be confirmed for the first time since its original isolation
      and it could be shown that it induces tubulin polymerization as efficiently as
      laulimalide.

PMID- 19402093
TI  - Metal-mediated [2+3] cycloaddition of nitrones to palladium-bound isonitriles.
AB  - The reactions between equimolar amounts of cis-[PdCl(2)(C[triple bond]NR)(2)] (R
      = cyclohexyl (Cy) 1, tBu 2, 2,6-Me(2)C(6)H(3) (Xyl) 3) and the acyclic nitrones
      O(+)N(R(2))=C(H)R(3) (R(2) = Me 5, R(2) = CH(2)Ph 6, R(3) = 4-MeC(6)H(4))
      proceeded in C(6)H(6) at 5 degrees C for around 4 h and then the reaction systems
      were maintained at 20-25 degrees C for 20 h to provide the carbene complexes
      [PdCl(2){C(ONR(2)C(c)HR(3)) = N(d)R}(C[triple bond]NR)(C(c)-N(d))] (8-13) in good
      yields (54-70%). The latter species originated from the previously unreported
      metal-mediated [2+3] cycloaddition of nitrones to coordinated isonitriles. For
      the reactions of cis-[PdCl(2)(C[triple bond]NR)(2)] (1-3) and 5 or 6 performed in
      C(6)H(6) at 20-25 degrees C, the selectivity of the cycloaddition was lost, and
      the reactions gave mixtures of 8-13 and the complexes
      [PdCl(2){N(R(2))=CHR(3)}(C[triple bond]NR)] (14-19, ca. 75%) derived from
      intramolecular deoxygenation of the nitrones. The reactions of equimolar amounts
      of cis-[PdCl(2)(C[triple bond]NR)(2)] (1-3 and R = 4-MeOC(6)H(4) 4) and the
      nonaromatic cyclic nitrone (-)O(+)N(a)=CHCH(2)CH(2)C(b)Me(2)(N(a)-C(b)) (7) in
      CHCl(3) at 5 degrees C for around 2 h led to the carbene species
      [PdCl(2){C(ON(a)CMe(2)CH(2)CH(2)C(b)H) = N(e)R}(C[triple bond]NR)(N(a)-C(b))(C(b)
      N(e))] (21-24), isolated in yields of 78-92%. When the reactions of cis
      [PdCl(2)(C[triple bond]NR)(2)] (1-4) and 7 (1:1 molar ratio) were performed in
      CHCl(3) at 20-25 degrees C for around 1 h, the carbenes 21-24 and the complexes
      [PdCl(2){N(f)CMe(2)CH(2)CH(2)C(g)H}(C[triple bond]NR)(N(f)-C(g))] (25-28, ca.
      35%), derived from the deoxygenation of 7, were identified by ESI(+)-MS and (1)H
      NMR analysis (after redissolution in CDCl(3)). The reactions of cis
      [PdCl(2)(C[triple bond]NR)(2)] (1-4) and 7 (1:2 molar ratio) in CHCl(3) at 5
      degrees C furnished mixtures of
      [PdCl(2){C(ON(a)CMe(2)CH(2)CH(2)C(b)H)=N(e)R}(N(f)CMe(2)CH(2)CH(2)C(g)H)(N(a)
      C(b))(C(b)-N(e))(N(f)-C(g))] (29-32; ca. 25-30%), 25-28 (ca. 10-15%), and
      [PdCl(2)(ON(a)CMe(2)CH(2)CH(2)C(b)H)(2)(N(a)-C(b))]. The same reactions at room
      temperature afforded the complex [PdCl(2)(N(f)CMe(2)CH(2)CH(2)C(g)H)(2)(N(f)
      C(g))] (33; ca. 20 %) in a mixture with 29-32 (ca. 5-10%) and 25-28.

PMID- 19402094
TI  - PTEN genomic deletion is associated with p-Akt and AR signalling in poorer
      outcome, hormone refractory prostate cancer.
AB  - PTEN haploinsufficiency is common in hormone-sensitive prostate cancer, though
      the incidence of genomic deletion and its downstream effects have not been
      elucidated in clinical samples of hormone refractory prostate cancer (HRPC).
      Progression to androgen independence is pivotal in prostate cancer and mediated
      largely by the androgen receptor (AR). Since this process is distinct from
      metastatic progression, we examined alterations of the PTEN gene in locally
      advanced recurrent, non-metastatic human HRPC tissues. Retrospective analyses of
      PTEN deletion status were correlated with activated downstream phospho-Akt (p
      Akt) pathway proteins and with the androgen receptor. The prevalence of PTEN
      genomic deletions in transurethral resection samples of 59 HRPC patients with
      known clinical outcome was assessed by four-colour FISH analyses. FISH was
      performed using six BAC clones spanning both flanking PTEN genomic regions and
      the PTEN gene locus, and a chromosome 10 centromeric probe. PTEN copy number was
      also evaluated in a subset of cases using single nucleotide polymorphism (SNP)
      arrays. In addition, the samples were immunostained with antibodies against p
      Akt, p-mTOR, p-70S6, and AR. The PTEN gene was deleted in 77% of cases, with 25%
      showing homozygous deletions, 18% homozygous and hemizygous deletions, and 34%
      hemizygous deletions only. In a subset of the study group, SNP array analysis
      confirmed the FISH findings. PTEN genomic deletion was significantly correlated
      to the expression of downstream p-Akt (p < 0.0001), AR (p = 0.025), and to cancer
      specific mortality (p = 0.039). PTEN deletion is common in HRPC, with bi-allelic
      loss correlating to disease-specific mortality and associated with Akt and AR
      deregulation.

PMID- 19402095
TI  - Preparation of enantiopure chiral amino-[D1]methyllithium compounds and
      determination of their micro- and macroscopic configurational stabilities.
AB  - Chiral amino-[D(1)]methyllithiums have been tested with regard to their
      microscopic and macroscopic configurational stabilities. The N-Boc-N
      diethoxyphosphinyl-substituted analogue immediately rearranged, showing complete
      retention of configuration at up to 0 degrees C. The N-Boc-N-PMB-protected
      analogue enantiomerized at -78 degrees C, but displayed an ee value of 65% at -95
      degrees C under macroscopic conditions when quenched with benzaldehyde seconds
      after its generation. Isocyanomethyllithium proved to be configurationally labile
      at this temperature and racemized completely, even on the microscopic timescale.
      Only the non-stabilized N,N-dibenzylaminomethyllithium was found to be virtually
      macroscopically configurationally stable below -95 degrees C.

PMID- 19402096
TI  - Low-molecular-weight dendrons for DNA binding and release by reduction-triggered
      degradation of multivalent interactions.
AB  - Losing the grip: The synthesis of multivalent low-molecular-weight dendrons with
      lysine branching units coupled to disulfide-linked spermine surface groups is
      described. It is furthermore demonstrated that the dendrons bind DNA with good
      affinity (see image), but are also able to release the DNA in a reductive
      environment.

PMID- 19402097
TI  - Metathesis-like splitting reactions of metallated
      [36]octaphyrins(1.1.1.1.1.1.1.1): experimental and computational investigations.
AB  - meso-Octakis(pentafluorophenyl)-substituted [36]octaphyrin(1.1.1.1.1.1.1.1) (1)
      is a figure-of-eight nonaromatic macrocycle that serves as a unique platform to
      induce a metathesis-like splitting reaction upon bis-Cu(II) metalation. To get a
      better understanding of this splitting reaction, we examined the metalation of 1
      with several metal ions. In contrast with the smooth and quantitative splitting
      reaction of bis-Cu(II) complex 1-CuCu, free-base 1, mono-Cu(II) complex 1-Cu, and
      bis-Zn(II) complex 1-ZnZn do not undergo the splitting reaction. Mono-Co(II)
      complex 1-Co was selectively produced from metalation with the Co(II) ion, from
      which hybrid complex 1-CoCu was synthesized. The hybrid complex 1-CoCu undergoes
      the splitting reaction to give 2-Co and 2-Cu quantitatively. Activation
      parameters of the splitting reactions were determined: E(a)=104 kJ mol(-1),
      DeltaH(double dagger)=101 kJ mol(-1), DeltaS(double dagger)=-25.0 J mol(-1) K(
      1), and DeltaV(double dagger)=18 cm(3) mol(-1) for 1-CuCu and E(a)=105 kJ mol(
      1), DeltaH(double dagger)=102 kJ mol(-1), and DeltaS(double dagger)=-29.9 J mol(
      1) K(-1) for 1-CoCu. A marked difference between the splitting reaction
      reactivity of 1-CuCu and 1-ZnZn has been examined by DFT calculations at the
      B3LYP/631SDD//B3LYP/LANL2DZ level, which revealed that the reaction proceeds
      through a stepwise route involving initial C1-C20 bond formation to give INT1 as
      the rate-determining step and subsequent C21-C40 bond formation to give a
      spirocyclobutane intermediate (INT2), followed by a radical reverse cycloaddition
      reaction to give two metalloporphyrins. Inherent instability of 1-CuCu, which may
      arise from its strongly distorted structure, was indicated to be a main factor in
      the smooth splitting reaction. Finally, a new bis-Pd(II) complex (5-PdPd) was
      isolated in the metalation of 1 with Pd(OAc)(2) in a 9:1 mixture of 2,2,2
      trifluoroethanol and methanol as a manifestation of the transannular electronic
      interaction in metalated octaphyrin complexes. Collectively, these results
      underscore the importance of the transannular electronic interactions that are
      enhanced by metalation, depending upon the coordinated metal ions.

PMID- 19402098
TI  - Transvaginal sonography for the assessment of ovarian and pelvic endometriosis:
      how deep is our understanding?

PMID- 19402099
TI  - Ultrasound is not unsound, but safety is an issue.

PMID- 19402100
TI  - Can quantitative three-dimensional power Doppler angiography be used to predict
      ovarian hyperstimulation syndrome?
AB  - OBJECTIVE: To test the hypothesis that ovarian vascularity is increased in women
      developing ovarian hyperstimulation syndrome (OHSS) and to assess its value as a
      predictor of OHSS during in-vitro fertilization (IVF). METHODS: 118 subjects
      undergoing their first cycle of IVF had a three-dimensional (3D) transvaginal
      ultrasound scan in the early follicular phase of the menstrual cycle preceding
      IVF treatment. 18 of them developed moderate or severe OHSS and 100 subjects had
      normal ovarian response. Antral follicle count, ovarian volume, and ovarian
      vascularity (vascularization index (VI), flow index (FI) and vascularization flow
      index (VFI)) were compared between OHSS and control groups. Multiple regression
      analysis was used to assess the predictive value of these variables against age,
      body mass index and basal follicle-stimulating hormone level for the development
      of OHSS. RESULTS: The ovarian blood flow indices VI (11.1 +/- 11.6 vs. 8.6 +/-
      7.3%; P = 0.23), FI (38.0 +/- 4.8 vs. 38.0 +/- 5.5; P = 0.95) and VFI (4.2 +/-
      3.3 vs. 3.5 +/- 3.1; P = 0.40) were similar in the OHSS group and the normal
      responders. While antral follicle count was significantly higher in women
      developing OHSS (33.0 +/- 15.1) than in the control group (19.2 +/- 9.9, P <
      0.001), ovarian volume did not differ between the two groups (10.6 +/- 3.8 vs.
      8.9 +/- 4.8 cm(3), respectively, P = 0.11). On multiple regression analysis,
      antral follicle count was the only significant predictor of OHSS (P < 0.01).
      CONCLUSIONS: Women developing OHSS during IVF do not demonstrate an increased
      ovarian blood flow as measured by 3D ultrasound but do have a significantly
      higher antral follicle count, which is the only significant predictor of OHSS.

PMID- 19402102
TI  - Fetal dilated cardiomyopathy caused by persistent junctional reciprocating
      tachycardia.
AB  - Ultrasound examination of a fetus at 32 weeks' gestation revealed dilated
      cardiomyopathy and a heart rate of 170 beats per minute. Prenatally, this mild
      tachycardia was not primarily suspected to be the cause of the myocardial
      changes. Postnatal electrocardiography revealed a persistent junctional
      reciprocating tachycardia (PJRT) and the diagnosis of tachycardia-induced
      cardiomyopathy (TICM) became apparent. After conversion to a sinus rhythm under
      digoxin and amiodarone, the cardiac changes regressed. PJRT is a rare form of
      supraventricular tachycardia. The prenatal findings in the condition have
      previously been described retrospectively, but it can only be diagnosed
      postnatally by its characteristic electrocardiographic properties. This case
      indicates that TICM can occur at lower heart rates than previously assumed. Even
      severe prenatal cardiomyopathy may be reversible once sinus rhythm has been
      restored.

PMID- 19402101
TI  - Role of uterine artery Doppler in interpreting low PAPP-A values in first
      trimester screening for Down syndrome in pregnancies at high risk of impaired
      placentation.
AB  - OBJECTIVES: Low maternal serum levels of pregnancy-associated plasma protein-A
      (PAPP-A) are associated with both increased risk of aneuploidies and impaired
      trophoblastic invasion, while high uterine artery (UtA) resistance is associated
      with impaired trophoblastic invasion but not with an increased risk of
      aneuploidies. The aim of this study was to determine whether high UtA resistance
      plays a role in explaining low PAPP-A levels in the absence of aneuploidies.
      METHODS: This was a prospective study of 116 singleton pregnancies at high risk
      for impaired placentation (having at least one major risk factor: prior history
      of pre-eclampsia, pregestational diabetes mellitus, chronic hypertension, chronic
      kidney disease, body mass index >30, autoimmune disorder, thrombophilia or
      recurrent pregnancy loss), booked for routine assessment of risk for aneuploidies
      by means of the first-trimester combined screening test (nuchal translucency
      thickness (NT) + PAPP-A + beta-human chorionic gonadotropin (beta-hCG)).
      Measurement of NT and the mean UtA pulsatility index (PI) were carried out at the
      11 to 13 + 6-week scan. All values were calculated in multiples of the median
      (MoM) adjusted for gestational age. A cut-off risk of 1/270 at time of sampling
      was adopted to differentiate high- from low-risk groups for trisomy 21. RESULTS:
      There were 108 patients deemed to be at low risk for trisomy 21 and eight at high
      risk. None had chromosomal defects, giving a false-positive rate for trisomy 21
      of 6.9%. The greatest differences between patients at low risk and those at high
      risk for trisomy 21 were found in their PAPP-A (0.98 vs. 0.38 MoM, P < 0.01) and
      beta-hCG (1.09 vs. 1.77 MoM, P = 0.04) values. Greater NT thickness (1.02 vs.
      0.90 MoM) and higher mean UtA-PI (1.05 vs. 0.96 MoM) were recorded in the high
      risk group, although the differences did not reach statistical significance (P =
      0.19 and 0.40, respectively). After log-transformation there were no significant
      correlations between mean UtA-PI and NT and between mean UtA-PI and beta-hCG.
      There was a significant negative linear correlation between mean UtA-PI and PAPP
      A (r = -0.331; P < 0.01). After adjusting the PAPP-A values by UtA-PI, the false
      positive rate for trisomy 21 decreased to 2.6%. CONCLUSION: Mean UtA-PI at the 11
      to 13 + 6-week scan may be an effect-modifier variable for PAPP-A that should be
      taken into account in the first-trimester combined screening for aneuploidies, at
      least in pregnancies at high risk for impaired placentation.

PMID- 19402103
TI  - Fetal intraperitoneal transfusion for iatrogenic twin anemia-polycythemia
      sequence after laser therapy.
AB  - Twin anemia-polycythemia sequence (TAPS) is a rare variant of twin-twin
      transfusion syndrome (TTTS) without the characteristic twin oligohydramnios
      polyhydramnios sequence and cardiovascular milieu attributed to renin-angiotensin
      system mediators. It can occur spontaneously or iatrogenically after fetoscopic
      laser surgery. We report the case of a woman, gravida 2 para 1, with a
      monochorionic diamniotic pregnancy who developed Quintero Stage III TTTS. She
      underwent laser photocoagulation of identifiable anastomotic vessels and
      subsequently developed suspected TAPS 2 weeks later. The pregnancy was
      successfully treated with serial intrauterine intraperitoneal transfusions (IUT
      PTs) of red blood cells. Although TAPS is a rare condition, serial middle
      cerebral artery peak systolic velocity measurements are warranted as follow-up in
      patients who have undergone fetoscopic laser surgery for TTTS. IUT-PTs may be
      superior to intravascular intrauterine transfusions in the treatment of this
      condition.

PMID- 19402104
TI  - Atomic force microscopy study of the role of LPS O-antigen on adhesion of E.
      coli.
AB  - The O-antigen is a highly variable component of the lipopolysaccharide (LPS)
      among Escherichia coli strains and is useful for strain identification and
      assessing virulence. While the O-antigen has been chemically well characterized
      in terms of sugar composition, physical properties such as O-antigen length of E.
      coli LPS have not been well studied, even though LPS length is important for
      determining binding of bacteria to biomolecules and epithelial cells. Atomic
      force microscopy (AFM) was used to characterize the physicochemical properties of
      the LPS of eight E. coli strains. Steric repulsion between the AFM tip (silicon
      nitride) and the E. coli cells was measured and modeled, to determine LPS lengths
      for three O157 and two O113 E. coli strains, and three control (K12) strains that
      do not express the O-antigen. For strains with an O-antigen, the LPS lengths
      ranged from 17 +/- 10 to 37 +/- 9 nm, and LPS length was positively correlated
      with the force of adhesion (F(adh)). Longer lengths of LPS may have allowed for
      more hydrogen bonding between the O-antigen and silanol groups of the AFM silicon
      nitride tip, which controlled the magnitude of F(adh). For control strains, LPS
      lengths ranged from 3 +/- 2 to 5 +/- 3 nm, and there was no relationship between
      LPS length and adhesion force between the bacterium and the silicon nitride tip.
      In the absence of the O-antigen, we attributed F(adh) to electrostatic
      interactions with lipids in the bacterial membrane.

PMID- 19402105
TI  - Adipocyte-hepatocyte crosstalk and the pathogenesis of nonalcoholic fatty liver
      disease.

PMID- 19402106
TI  - The structure behind diversity: covariance networks in hepatitis C virus
      sequences are associated with treatment response.

PMID- 19402107
TI  - Insulin resistance is a risk factor for esophageal varices in hepatitis C virus
      cirrhosis.

PMID- 19402109
TI  - Glutathione S-transferase M1 and T1 null genotypes increase susceptibility to
      drug-induced liver injury.

PMID- 19402110
TI  - Ascites and variceal bleeding occurring in a 20-year-old with cystic fibrosis.

PMID- 19402113
TI  - Values for upper limit of normal should be given for liver enzymes.

PMID- 19402114
TI  - Closing the gap: the tight junction protein occludin and hepatitis C virus entry.

PMID- 19402116
TI  - Hemochromatosis: platelets and aspartate aminotransferase are useful high-degree
      fibrosis marker.

PMID- 19402118
TI  - Hepatitis B virus clearance rate estimates.

PMID- 19402120
TI  - Interobserver repeatability of three- and four-dimensional transperineal
      ultrasound assessment of pelvic floor muscle anatomy and function.
AB  - OBJECTIVE: To evaluate the interobserver repeatability of measurement of the
      pubovisceral muscle and levator hiatus, and the position of related organs,
      during rest, muscle contraction and Valsalva maneuver using three- and four
      dimensional (3D and 4D) transperineal ultrasound. METHODS: Seventeen women were
      included in the study. The position and dimensions of the pubovisceral muscle and
      levator hiatus in patients at rest and during contraction and Valsalva were
      determined from stored 3D and 4D ultrasound volumes. Analyses were conducted
      offline by two observers blinded to the clinical data and to each others'
      measurements. RESULTS: Measurements of levator hiatal dimensions at rest
      demonstrated intraclass correlation coefficient (ICC) values of 0.92 to 0.96. The
      ICC values for pubovisceral muscle thickness at rest varied between good and very
      good (ICC, 0.61-0.93), regardless of plane. During contraction, the ICC values
      for all measured parameters were very good, varying between 0.61 and 0.92.
      Measurement of the transverse diameter of the levator hiatus during the Valsalva
      maneuver showed good reliability (ICC, 0.86), but assessment of the anterior and
      posterior borders of the levator hiatus was only possible in 29% of cases.
      CONCLUSIONS: 3D and 4D transperineal ultrasound measurement of the pubovisceral
      muscle and levator hiatus is reliable in women with no or minor symptoms of
      prolapse at rest and during contraction. The technique for recording during the
      Valsalva maneuver requires improvement if it is to be useful in the diagnosis of
      pelvic organ prolapse.

PMID- 19402121
TI  - Investigations on the leaf surface ultrastructure in grapevine (Vitis vinifera
      L.) by scanning microscopy.
AB  - Several Scanning microscopy techniques were used to investigate the leaf surface
      ultrastructure in the local "Razegui" grapevine cultivar (Vitis vinifera L.).
      Conventional scanning electron microscopy performed on glutaraldehyde-fixed
      samples allowed observation of well-preserved epidermal cells with an overlaying
      waxy layer. At a high magnification, the waxy layer exhibited crystalline
      projections in the form of horizontal and vertical platelets. Also, to avoid
      eventual ultrastructural alterations inherent in the use of solvents during
      sample preparation, fresh leaf blade samples were directly observed by
      environmental scanning electron microscopy. A classical image of convex living
      epidermal cells was observed. At 2400x magnification, epicuticular waxes
      exhibited a granular structure. However, high-magnification images were not
      obtained with this device. The atomic force microscopy (AFM) performed on fresh
      leaf blade samples allowed observation of a textured surface and heterogeneous
      profiles attributed to epicuticular wax deposits. AFM topography images confirmed
      further, the presence of irregular crystalloid wax projections as multishaped
      platelets on the adaxial surface of grapevine leaf.

PMID- 19402122
TI  - Three-dimensional power Doppler imaging of uterine artery pseudoaneurysm treated
      unsuccessfully with selective embolization.

PMID- 19402123
TI  - The impact of crown-rump length measurement error on combined Down syndrome
      screening: a simulation study.
AB  - OBJECTIVE: To evaluate the impact of a 5-mm error in the measurement of crown
      rump length (CRL) in a woman undergoing ultrasound and biochemistry sequential
      combined screening for Down syndrome. METHODS: Based on existing risk calculation
      algorithms, we simulated the case of a 35-year-old-woman undergoing combined
      screening based on nuchal translucency (NT) measurement and early second
      trimester maternal serum markers (human chorionic gonadotropin (hCG) and alpha
      fetoprotein (AFP) expressed as multiples of the median (MoM)). Two measurement
      errors were considered (+ or - 5 mm), for four different CRLs (50, 60, 70 and 80
      mm), with five different NT measurements (1, 1.5, 2, 2.5 and 3 mm) in a patient
      undergoing biochemistry testing at 14 + 4, 15, 16, 17 or 18 weeks' gestation.
      Four different values for each maternal serum marker were tested (1, 1.5, 2 and
      2.5 MoM for hCG, and 0.5, 0.8, 1 and 1.5 MoM for AFP), leading to a total of 3200
      simulations of the impact of measurement error. In all cases the ratio between
      the risk as assessed with or without the measurement error was calculated
      (measurement error-related risk ratio (MERR)). RESULTS: Over 3200 simulated
      cases, MERR ranged from 0.53 to 2.14. In 586 simulations (18.3%), it was < 0.66
      or > 1.33. Based on a risk cut-off of 1/300, women would have been misclassified
      in 112 simulations (3.5%). This would go up to 33 (27.5%) out of the 120
      simulations in women with 'borderline' risk, with 1.5 MoM for hCG and 0.5 MoM for
      AFP, and NT measurement of 1 or 2mm. CONCLUSION: Down syndrome screening may be
      highly sensitive to measurement errors in CRL. Quality control of CRL measurement
      should be performed together with quality control of NT measurement in order to
      provide the highest standard of care.

PMID- 19402125
TI  - ISUOG Statement on the non-medical use of ultrasound, 2009.

PMID- 19402126
TI  - The histone deacetylase inhibitor LBH589 inhibits expression of mitotic genes
      causing G2/M arrest and cell death in head and neck squamous cell carcinoma cell
      lines.
AB  - Head and neck squamous cell carcinoma represents a complex set of neoplasms
      arising in diverse anatomical locations. The site and stage of the cancer
      determine whether patients will be treated with single or multi-modality therapy.
      The HDAC inhibitor LBH589 is effective in treating some haematological neoplasms
      and shows promise for certain epithelial neoplasms. As with other human cancer
      cell lines, LBH589 causes up-regulation of p21, G2/M cell cycle arrest, and cell
      death of human HNSCC cell lines, as measured using flow cytometry and cDNA
      microarrays. Global RNA expression studies following treatment of the HNSCC cell
      line FaDu with LBH589 reveal down-regulation of genes required for chromosome
      congression and segregation (SMC2L1), sister chromatid cohesion (DDX11), and
      kinetochore structure (CENP-A, CENP-F, and CENP-M); these LBH589-induced changes
      in gene expression coupled with the down-regulation of MYC and BIRC5 (survivin)
      provide a plausible explanation for the early mitotic arrest and cell death
      observed. When LBH589-induced changes in gene expression were compared with gene
      expression profiles of 41 primary HNSCC samples, many of the genes that were down
      regulated by LBH589 showed increased expression in primary HNSCC, suggesting that
      some patients with HNSCC may respond to treatment with LBH589.

PMID- 19402128
TI  - Innovations and challenges in renal cancer: Proceedings of the 3rd Cambridge
      Conference, June 27-28, 2008, Cambridge, Massachusetts, USA.

PMID- 19402127
TI  - The safe use of non-medical ultrasound: a summary of the proceedings of the joint
      safety symposium of ISUOG and WFUMB.

PMID- 19402129
TI  - met oncogene activation qualifies spontaneous canine osteosarcoma as a suitable
      pre-clinical model of human osteosarcoma.
AB  - The Met receptor tyrosine kinase (RTK) is aberrantly expressed in human
      osteosarcoma and is an attractive molecular target for cancer therapy. We studied
      spontaneous canine osteosarcoma (OSA) as a potential pre-clinical model for
      evaluation of Met-targeted therapies. The canine MET oncogene exhibits 90%
      homology compared with human MET, indicating that cross-species functional
      studies are a viable strategy. Expression and activation of the canine Met
      receptor were studied utilizing immunohistochemical techniques in 39 samples of
      canine osteosarcoma, including 35 primary tumours and four metastases. Although
      the Met RTK is barely detectable in primary culture of canine osteoblasts, high
      expression of Met protein was observed in 80% of canine osteosarcoma samples
      acquired from various breeds. Met protein overexpression was also concordant with
      its activation as indicated by phosphorylation of critical tyrosine residues. In
      addition, Met was expressed and constitutively activated in canine osteosarcoma
      cell lines. OSA cells expressing high levels of Met demonstrated activation of
      downstream transducers, elevated spontaneous motility, and invasiveness which
      were impaired by both a small molecule inhibitor of Met catalytic activity (PHA
      665752) and met-specific, stable RNA interference obtained by means of lentiviral
      vector. Similar to observations in human OSA, these data suggest that Met is
      commonly overexpressed and activated in canine OSA and that inhibition of Met
      impairs the invasive and motogenic properties of canine OSA cells. These data
      implicate Met as a potentially important factor for canine OSA progression and
      indicate that it represents a viable model to study Met-targeted therapies.

PMID- 19402130
TI  - Conflict and resolution between phylogenies inferred from molecular and
      phenotypic data sets for hagfish, lampreys, and gnathostomes.
AB  - One of the most problematic issues in vertebrate phylogenetics is the
      disagreement between phenotypic and molecular inferences regarding the
      relationships among hagfishes, lampreys, and gnathostomes. Phenotypic characters
      support monophyly of lampreys and gnathostomes, whereas nearly all published
      analyses of molecular data sets support monophyly of hagfishes and lampreys. In
      this study I present results of phylogenetic analyses of combined phenotypic and
      molecular data sets that focus on relationships among hagfishes, lampreys, and
      gnathostomes. Maximum parsimony analyses of 115 phenotypic characters combined
      with 4,638 rRNA sites and more than 10,000 amino acids each result in monophyly
      of lampreys and gnathostomes, demonstrating that the addition of relatively few
      phenotypic characters can alter phylogenetic inferences from large molecular data
      sets. On the other hand, Bayesian analyses of the combined data sets support
      monophyly of hagfish and lampreys, indicating that model-based analyses may be
      prone to data "swamping," where the phylogenetic signal of the larger molecular
      data sets overwhelm the signal present in the much smaller phenotypic data set.
      Nodes that relate hagfish and lampreys were recovered at a low frequency in
      parametric bootstrapping analyses, indicating that the timing of diversification
      among hagfishes, lampreys, and gnathostomes has created a difficult phylogenetic
      problem for molecular data. The fact that addition of relatively few phenotypic
      characters can alter phylogenetic inferences of cyclostome monophyly obtained
      from molecular data sets, and the inability of simulated data sets to recover key
      nodes in the craniate phylogeny provide reasons to view the strong support for
      cyclostome monophyly inferred from molecular data sets with a measured degree of
      skepticism.

PMID- 19402133
TI  - Fin regeneration from tail segment with musculature, endoskeleton, and scales.
AB  - It is well known that fish caudal fins can be completely regenerated after fin
      amputation. Although much research on fin regeneration has been carried out,
      there have been very few reports regarding fin regeneration after tail
      amputation. In this study, we used grass carp, common carp, koi carp, and
      zebrafish as experimental organisms. Some caudal fins could be distinctly
      regenerated in 2 weeks after tail amputation. After all-trans-retinoic acid
      treatment and tail amputation, zebrafish were unable to regenerate caudal fins
      that could be seen with the naked eye. However, after tail amputation, more than
      half of the zebrafish tested were able to regenerate caudal fins. Caudal fin
      regeneration depended on the presence of musculature and endoskeleton at the site
      of amputation. These caudal fins arose from segments of the endoskeleton, which
      contrast with currently accepted knowledge.

PMID- 19402132
TI  - Genomic and phenotypic analysis reveals a key role for CCN1 (CYR61) in BAG3
      modulated adhesion and invasion.
AB  - Chaperone protein quantity may regulate the balance of proteins involved in
      invasion and malignancy. BAG3 is a co-chaperone and pro-survival protein that has
      been implicated in adhesion, migration, and metastasis. We reported that BAG3
      overexpression in MDA435 human breast cancer cells results in a significant
      decrease in migration and adhesion to matrix molecules that is reversed upon
      deletion of the BAG3 proline-rich domain (dPXXP). We now hypothesize that
      transcriptional analysis would identify proteins involved in matrix-related
      processes that are regulated by BAG3 and/or its PXXP domain mutant. Expression
      array analysis of MDA435 cells overexpressing either wild-type BAG3 (FL) or dPXXP
      identified CCN1 as a BAG3 target protein. CCN1 is a known AP-1 target. Increased
      AP-1 transcriptional activity and AP-1 DNA-binding was found in MDA435 dPXXP
      cells. Consistent with these findings, CCN1 quantity and secretion were increased
      in dPXXP mutants but suppressed in FL cells; both BAG3 forms resulted in up
      regulated CCN1 in HeLa cells. CCN1 silencing in the BAG3 FL overexpressors
      reduced the already low phospho-integrin beta1 in response to attachment on
      collagen IV. Matrigel invasion of HeLa cells engineered with the BAG3 constructs
      was enhanced in FL cells and minimal in dPXXP cells. CCN1 silencing blocked a
      greater percentage of the serum-induced invasion in FL cells than in dPXXP cells.
      This implies a context-dependent function of BAG3 on CCN1 and thus mesenchymal
      behaviour. CCN1 may be necessary for adhesion and matrix-related signalling in FL
      cells, abrogating a negative signal of the PXXP domain when BAG3 is intact. We
      propose that BAG3 regulates CCN1 expression to regulate tumour cell adhesion and
      migration.

PMID- 19402134
TI  - Thiotaurine and hypotaurine contents in hydrothermal-vent polychaetes without
      thiotrophic endosymbionts: correlation With sulfide exposure.
AB  - Invertebrates at hydrothermal vents and cold seeps must cope with toxic H(2)S.
      One proposed protection mechanism involves taurine derivatives: At vents and
      seeps, many animals have high levels of hypotaurine and thiotaurine (a product of
      hypotaurine and HS), originally found in animals with thiotrophic endosymbionts.
      To further test the role of these compounds, we analyzed them in vent polychaetes
      without endosymbionts: Paralvinella sulfincola, P. palmiformis and P. pandorae
      (paralvinellids) and Nicomache venticola (maldanid). P. sulfincola were collected
      from a high temperature (42-68 degrees C) and a warm site (21-35 degrees C). P.
      palmiformis and pandorae were from cool sites (12-18 degrees C) and N. venticola
      were from a cold site (4 degrees C). H(2)S concentrations in vent effluent
      largely correlate with temperature. Some specimens were frozen; other ones were
      kept alive in laboratory chambers, with and without sulfide. Tissues were
      analyzed for taurine derivatives and other solutes that serve as organic
      osmolytes. The major osmolyte of all species was glycine. Thiotaurine contents
      were significantly different among all species, in the order P. sulfincola hot>P.
      sulfincola warm>P. pandorae>P. palmiformis>N. venticola. P. sulfincola also had
      high levels of sarcosine; others species had none. Sarcosine and hypotaurine
      contents of P. sulfincola's branchiae were higher, while glycine contents were
      lower, than in main body. In P. palmiformis kept in pressure chambers with
      sulfide, thiotaurine contents were higher and hypotaurine lower than in those
      kept without sulfide. These results support the hypothesis that conversion of
      hypotaurine to thiotaurine detoxifies sulfide in vent animals without
      endosymbionts.

PMID- 19402135
TI  - Validation of simplified diagnostic criteria for autoimmune hepatitis in Italian
      patients.

PMID- 19402136
TI  - Additive effects of hyperbaric oxygen and platelet-derived growth factor-BB in
      chondrocyte transplantation via up-regulation expression of platelet-derived
      growth factor-beta receptor.
AB  - The present study investigated the effects of hyperbaric oxygen (HBO) and
      platelet-derived growth factor-BB (PDGF-BB) in chondrocyte transplantation. In
      vitro, chondrocytes were treated with HBO, PDGF-BB, and HBO combined with PDGF-BB
      (H+P). Cell growth was analyzed using cell counting, MTT assay, and FACS
      analysis. mRNA expression of the PDGF-alpha receptor (PDGFR-alpha) and beta
      receptor (PDGFR-beta) was detected by RT-PCR. Protein expression of PDGFR-beta
      was detected by Western blotting. In vivo, chondrocytes and PDGF-BB were
      suspended in alginate as a transplantation system. Cartilage defects were grafted
      with this system and with or without HBO treatment. Released PDGF-BB
      concentration was quantified by ELISA. After 8 weeks, animals were sacrificed and
      the repaired tissues were examined. In vitro data suggested that each treatment
      increased cell growth via the up-regulated mRNA expression of PDGFR-alpha and
      increased cell accumulation in the S-phase. The H+P treatment was more additive
      in cell growth and in mRNA and protein expression of PDGFR-beta than HBO or PDGF
      BB. In vivo results suggested that PDGF-BB delivery lasted for more than 5 weeks.
      Scoring results showed that each treatment significantly increased the cartilage
      repair. Safranin-O and type II collagen staining confirmed the hyaline-like
      cartilage regeneration in the repaired tissues. In situ up-regulation of PDGFR
      beta expression partially explains the additive effect of H+P treatment in
      cartilage repair. Accordingly, H+P offers a potential treatment method for
      cartilage repair.

PMID- 19402137
TI  - Effect of bone sialoprotein coating of ceramic and synthetic polymer materials on
      in vitro osteogenic cell differentiation and in vivo bone formation.
AB  - In this study, we addressed whether Bone Sialoprotein (BSP) coating of various
      substrates could enhance the in vitro osteogenic differentiation and in vivo bone
      formation capacity of human Bone Marrow Stromal Cells (BMSC). Moreover, we tested
      whether synthetic polymer-based porous scaffolds, despite the absence of a
      mineral component, could support ectopic bone formation by human BMSC if coated
      with BSP. Adsorption of recombinant human BSP on tissue culture-treated
      polystyrene (TCTP), beta-tricalcium phosphate (Osteologic) or synthetic polymer
      (Polyactive) substrates was dose dependent, but did not consistently accelerate
      or enhance in vitro BMSC osteogenic differentiation, as assessed by the mRNA
      expression of osteoblast-related genes. Similarly, BSP coating of porous beta
      tricalcium phosphate scaffolds (Skelite) did not improve the efficiency of bone
      tissue formation following loading with BMSC and ectopic implantation in nude
      mice. Finally, Polyactive foams seeded with BMSC did not form bone tissue in the
      same ectopic assay, even if coated with BSP. We conclude that BSP coating of a
      variety of substrates is not directly associated with an enhancement of
      osteoprogenitor cell differentiation in vitro or in vivo, and that presentation
      of BSP on polymeric materials is not sufficient to prime BMSC functional
      osteoblastic differentiation in vivo.

PMID- 19402139
TI  - Uncoupled investigation of scaffold modulus and mesh size on smooth muscle cell
      behavior.
AB  - Although scaffold material properties are known to critically impact cell
      behavior, it has proven difficult to correlate specific cell responses to
      isolated scaffold parameters, inhibiting rational design of scaffold material
      properties. The aim of this study was to validate a systematic approach for
      evaluating the influence of initial scaffold modulus and mesh size on cell
      extracellular matrix (ECM) deposition and phenotype. Poly(ethylene glycol)
      diacrylate (PEGDA) hydrogels were selected for this study because of their
      tunable material properties. Following screening of six distinct PEGDA hydrogels,
      three formulations were identified which permitted uncoupled investigation of
      scaffold mesh size and modulus within the target incremental modulus range of
      approximately 100-300 kPa. Smooth muscle cells (SMCs) were encapsulated within
      these three formulations, and cell ECM deposition and phenotype were evaluated
      following 21 days of culture. Although elastin content appeared to be correlated
      with scaffold mesh size and modulus to a similar degree, levels of collagen and
      serum response factor (SRF), a key regulator of SMC phenotype, were more strongly
      correlated with mesh size. To gain insight into the cell signaling underlying
      these observed correlations, variations in cell metabolic state and in RhoA
      signaling were semi-quantitatively evaluated. Both RhoA activity, which is
      largely modulated by scaffold mechanics in 2D, and cell metabolic activity were
      highly correlated with hydrogel mesh size. These results indicate that the
      effects of scaffold mechanics on RhoA activity in 3D may be distinct from those
      in 2D and underscore the need for uncoupled investigation of scaffold parameters
      on cell behavior. Furthermore, the present data suggest that RhoA signaling and
      cell metabolic regulation may be closely linked.

PMID- 19402138
TI  - Size-tunable synthesis of stable superparamagnetic iron oxide nanoparticles for
      potential biomedical applications.
AB  - Dextran-coated superparamagnetic nanoparticles (MNPs) have widespread biomedical
      applications. The superparamagnetic behavior, specifically regulated size, and
      smooth morphology are crucial requirements for essentially all of these
      applications. Presented herein is an innovative double-coating strategy that
      would allow for a size-controlled synthesis of MNPs. Small monocrystalline iron
      oxide nanoparticles (MIONs) were first synthesized, which served as the source of
      superparamagnetic properties. These MIONs were then treated in an acetate buffer
      containing biocompatible dextran polymer. Under such an environment, the
      colloidal MIONs would be quickly agglomerated by the acetate ions, and the formed
      coalescent body of MION would then be stabilized simultaneously by coating with
      dextran. By regulating the MION or dextran concentration as well as the thermal
      incubation time, the sizes of these first formed nanoparticles (termed 1st-NPs)
      could be readily controlled. A second dextran coating step was further applied to
      smoothen the 1st-NPs in attaining a final product (termed 2nd-NPs). The 2nd-NPs
      exhibited robust storage stability because of the additional coating shell.
      Results successfully confirmed the plausibility of this approach, as these MNPs
      displayed not only a smooth outline and a narrow size distribution but also the
      essential superparamagnetic behavior and a significantly prolonged stability on
      storage.

PMID- 19402140
TI  - A study on the influence of biocompatible composites with bioactive ligands
      toward their effect on cell adhesion and growth for the application in bone
      tissue engineering.
AB  - The aim of this study was the transformation of the macroporous zirconium dioxide
      ceramic Sponceram into a biomimetic composite material. To enhance the adhesion
      of cells and to induce their differentiation into osteoblasts poly-L-lysine and
      BMP-2 were coupled to polymers and copolymers based on 2-deoxy-N-methacrylamido-D
      glucose (ox.p(MAG) and p(MVA)) used as spacer, which were adsorbed onto the
      ceramic surface. The development of the composite materials was validated step by
      step qualitatively and quantitatively. The bioactive potential of the composite
      materials was tested under static and dynamic conditions using an osteoblastic
      model cell line and human mesenchymal stem cells. Both composite materials showed
      potential to enhance the adhesion of cells in the first 10 days of their
      cultivation. One of the composite materials, namely Sponceram/ox.p(MAG)-BMP-2,
      was tested into a rotating-bed bioreactor with regard to its osteogenic
      differentiation-inducing potential. Compared with Sponceram modified with BMP-2
      without a polymer spacer, it showed increased expression of osteogenic markers
      determined by PCR analysis. In summary, the in vitro testing of the developed
      composite materials demonstrated a promising potential for their application as
      biomimetic scaffold materials with controllable properties.

PMID- 19402141
TI  - Calcium phosphate/DNA co-precipitates encapsulated fast-degrading polymer films
      for substrate-mediated gene delivery.
AB  - Calcium-phosphate/deoxyribose nucleic acid (Ca-P/DNA) co-precipitates were
      deposited on or encapsulated in fast-degrading polymer films with surface erosion
      degradation mechanism to mediate cell transfection. The polymer, cholic acid
      functionalized star poly(DL-lactide), was synthesized through the ring-opening
      polymerization of DL-lactide initiated by cholic acid. The releases of DNA from
      the Ca-P/DNA co-precipitates deposited film and the Ca-P/DNA co-precipitates
      encapsulated film were determined and compared. The in vitro gene transfections
      of HEK293 cells, Hela cells, and NIH 3T3 cells showed that the expression of pGL3
      Luc plasmid could be effectively mediated by the Ca-P/DNA co-precipitates
      deposited and encapsulated polymer films. In addition, the films did not exhibit
      any additional cytotoxicity to the cells during the transfections, indicating
      that the fast-degrading polymer films have great potential in localized gene
      delivery.

PMID- 19402142
TI  - Solvent-dependent conformation of amylose tris(phenylcarbamate) as deduced from
      scattering and viscosity data.
AB  - The z-average mean-square radius of gyration S(2)(z), the particle scattering
      function P(k), the second virial coefficient, and the intrinsic viscosity [eta]
      have been determined for amylose tris(phenylcarbamate) (ATPC) in methyl acetate
      (MEA) at 25 degrees C, in ethyl acetate (EA) at 33 degrees C, and in 4-methyl-2
      pentanone (MIBK) at 25 degrees C by light and small-angle X-ray scattering and
      viscometry as functions of the weight-average molecular weight in a range from 2
      x 10(4) to 3 x 10(6). The first two solvents attain the theta state, whereas the
      last one is a good solvent for the amylose derivative. Analysis of the S(2)(z),
      P(k), and [eta] data based on the wormlike chain yields h (the contour length or
      helix pitch per repeating unit) = 0.37 +/- 0.02 and lambda(-1) (the Kuhn segment
      length) = 15 +/- 2 nm in MEA, h = 0.39 +/- 0.02 and lambda(-1) = 17 +/- 2 nm in
      EA, and h = 0.42 +/- 0.02 nm and lambda(-1) = 24 +/- 2 nm in MIBK. These h
      values, comparable with the helix pitches (0.37-0.40 nm) per residue of amylose
      triesters in the crystalline state, are somewhat larger than the previously
      determined h of 0.33 +/- 0.02 nm for ATPC in 1,4-dioxane and 2-ethoxyethanol, in
      which intramolecular hydrogen bonds are formed between the C==O and NH groups of
      the neighbor repeating units. The slightly extended helices of ATPC in the ketone
      and ester solvents are most likely due to the replacement of those hydrogen bonds
      by intermolecular hydrogen bonds between the NH groups of the polymer and the
      carbonyl groups of the solvent.

PMID- 19402143
TI  - A spectroscopic investigation into the interactions of 3'-O-carboxy esters of
      thymidine with bovine serum albumin.
AB  - Binding studies of 3'-O-carboxy esters of thymidine, reported inhibitors of
      ribonucleases, with bovine serum albumin (BSA) have been explored in this report.
      Fluorescence spectroscopy in combination with Fourier transform infrared (FTIR)
      and circular dichroism (CD) spectroscopy have been used to determine the nature
      and mode of binding. The binding and quenching parameters were determined from
      tryptophan fluorescence quenching by Scatchard plots and modified Stern-Volmer
      plots. The association constants are of the order of 10(4) M(-1) for both the
      ligands. Thermodynamic parameters suggest that apart from an initial hydrophobic
      association, hydrogen bonding and van der Waals interactions play a decisive role
      during protein-ligand complex formation. Minor changes were observed in the
      secondary structures of human serum albumin (HSA) as revealed by FTIR and CD.
      Docking studies suggest that the ligands are close to Trp 213, which causes
      fluorescence quenching.

PMID- 19402145
TI  - Partition of thermodynamic energies of drug-DNA complexation.
AB  - We report a computation methodology, which leads to the ability to partition the
      Gibb's free energy for the complexation reaction of aromatic drug molecules with
      DNA. Using this approach, it is now possible to calculate the absolute values of
      the energy contributions of various physical factors to the DNA binding process,
      whose summation gives a value that is reasonably close to the experimentally
      measured Gibb's free energy of binding. Application of the methodology to binding
      of various aromatic drugs with DNA provides an answer to the question "What
      forces are the main contributors to the stabilization of aromatic ligand-DNA
      complexes?"

PMID- 19402144
TI  - Study of the interactions between a proline-rich protein and a flavan-3-ol by
      NMR: residual structures in the natively unfolded protein provides anchorage
      points for the ligands.
AB  - Astringency is one of the major organoleptic properties of food and beverages
      that are made from plants, such as tea, chocolate, beer, or red wine. This
      sensation is thought to be due to interactions between tannins and salivary
      proline-rich proteins, which are natively unfolded proteins. A human salivary
      proline-rich protein, namely IB-5, was produced by the recombinant method. Its
      interactions with a model tannin, epigallocatechin gallate (EGCG), the major
      flavan-3-ol in green tea, were studied here. Circular dichroism experiments
      showed that IB-5 presents residual structures (PPII helices) when the ionic
      strength is close to that in saliva. In the presence of these residual
      structures, IB-5 undergoes an increase in structural content upon binding to
      EGCG. NMR data corroborated the presence of preformed structural elements within
      the protein prior to binding and a partial assignment was proposed, showing
      partial structuration. TOCSY experiments showed that amino acids that are
      involved in PPII helices are more likely to interact with EGCG than those in
      random coil regions, as if they were anchorage points for the ligand. The signal
      from IB-5 in the DOSY NMR spectrum revealed an increase in polydispersity upon
      addition of EGCG while the mean hydrodynamic radius remained unchanged. This
      strongly suggests the formation of IB-5/EGCG aggregates.

PMID- 19402146
TI  - Wear and hardness of different core build-up materials.
AB  - Before crown preparation, teeth with extensive coronal destructions are built up
      with core materials. Sometimes, these build ups are exposed to the oral
      environment without the protection of crowns. Therefore, this in vitro
      investigation was aimed at evaluating the wear, surface roughness, Vickers
      hardness, and surface structure of 10 core composites, two glass ionomer cements
      (GICs), and four posterior restoration composites. The three-body wear was tested
      after water storage and 2,00,000 cycles. We measured both surface roughness and
      Vickers hardness (DIN 50133) and evaluated the surface structures by scanning
      electron microscopy. Results were statistically analyzed by use of the Mann
      Whitney U test (alpha = 0.05). Lowest wear was found for the restorative
      composites (20 microm Grandio; others about 40 microm). A comparison of the
      composites Build-It, Chroma Core, Rebilda LC, and Rebilda DC to Quixfil showed
      similar wear values for each material (43-50 microm). Wear values of GICs and all
      others core composites ranged between 58 and 75 microm. Only Ti-Core showed
      significantly higher wear than all other materials (p < 0.05). All core materials
      except Ti-Core (35 HV) showed Vickers hardness values between 42 and 61 HV. Most
      core composites, particularly Build-It, Multicore Flow, Rebilda LC, Ecusit, and
      Tetric Evo Ceram, showed more homogenous surface structures compared to GICs and
      restorative composites. Therefore, wear values of core build-up materials not
      only differed widely but were higher than those of conventional restorative
      materials; yet, core build-up materials showed advantageous surface structures.

PMID- 19402148
TI  - Functional sensibility assessment. Part II: Effects of sensory improvement on
      precise pinch force modulation after transverse carpal tunnel release.
AB  - Patients with median nerve compression at the carpal tunnel often have poor
      sensory afferents. Without adequate sensory modulation control, these patients
      frequently exhibit clumsy performance and excessive force output in the affected
      hand. We analyzed precision grip function after the sensory recovery of patients
      with carpal tunnel syndrome (CTS) who underwent carpal tunnel release (CTR).
      Thirteen CTS patients were evaluated using a custom-designed pinch device and
      conventional sensory tools before and after CTR to measure sensibility, maximum
      pinch strength, and anticipated pinch force adjustments to movement-induced load
      fluctuations in a pinch-holding-up activity. Based on these tests, five force
      related parameters and sensory measurements were used to determine improvements
      in pinch performance after sensory recovery. The force ratio between the exerted
      pinch force and maximum load force of the lifting object was used to determine
      pinch force coordination and to prove that CTR enabled precision motor output.
      The magnitude of peak pinch force indicated an economic force output during
      manipulations following CTR. The peak pinch force, force ratio, and percentage of
      maximum pinch force also demonstrated a moderate correlation with the Semmes
      Weinstein test. Analysis of these tests revealed that improved sensory function
      helped restore patients' performance in precise pinch force control evaluations.
      These results suggest that sensory information plays an important role in
      adjusting balanced force output in dexterous manipulation.

PMID- 19402147
TI  - Calcium aluminate coated and uncoated free form fabricated CoCr implants: a
      comparative study in rabbit.
AB  - The purpose of this study was to compare the integration in bone of uncoated free
      form fabricated cobalt chromium (CoCr) implants to the same implant with a
      calcium aluminate coating. The implants of cylindrical design with a pyramidal
      surface structure were press-fit into the limbs of New Zealand white rabbits.
      After 6 weeks, the rabbits were sacrificed, and samples were retrieved and
      embedded. Ground sections were subjected to histological analysis and
      histomorphometry. The section counter part was used for preparing an electron
      transparent transmission electron microscopy sample by focused ion beam milling.
      Calcium aluminate dip coating provided a significantly greater degree of bone
      contact than that of the native CoCr. The gibbsite hydrate formed in the
      hardening reaction of the calcium aluminate was found to be the exclusive
      crystalline phase material in direct contact with bone.

PMID- 19402149
TI  - Lower extremity walking mechanics of young individuals with asymptomatic varus
      knee alignment.
AB  - Varus knee alignment is associated with an increased risk for developing medial
      knee osteoarthritis (OA). Medial knee OA is commonly associated with altered
      walking mechanics in the frontal and sagittal planes, as well as altered ground
      reaction forces. It is unknown whether these mechanics are present in young,
      asymptomatic individuals with varus knees. We expected that varus-aligned
      individuals would generally present with frontal plane mechanics that were
      similar to those reported for individuals with medial knee OA. The gait mechanics
      of 17 asymptomatic individuals with varus knees and 17 healthy, normally aligned
      controls were recorded. Gait parameters associated with medial knee OA were
      compared between groups. The individuals with varus knees exhibited greater knee
      external adduction moments, knee adduction, eversion, and lateral ground reaction
      force than the normally aligned individuals. In addition, those with varus knees
      also demonstrated increased knee flexion and external knee flexor moments during
      midstance. These results suggest that individuals with varus knees exhibit some,
      but not all, of the altered mechanics seen in medial knee OA.

PMID- 19402150
TI  - Drilling and microfracture lead to different bone structure and necrosis during
      bone-marrow stimulation for cartilage repair.
AB  - Bone marrow stimulation is performed using several surgical techniques that have
      not been systematically compared or optimized for a desired cartilage repair
      outcome. In this study, we investigated acute osteochondral characteristics
      following microfracture and comparing to drilling in a mature rabbit model of
      cartilage repair. Microfracture holes were made to a depth of 2 mm and drill
      holes to either 2 mm or 6 mm under cooled irrigation. Animals were sacrificed 1
      day postoperatively and subchondral bone assessed by histology and micro-CT. We
      confirmed one hypothesis that microfracture produces fractured and compacted bone
      around holes, essentially sealing them off from viable bone marrow and
      potentially impeding repair. In contrast, drilling cleanly removed bone from the
      holes to provide access channels to marrow stroma. Our second hypothesis that
      drilling would cause greater osteocyte death than microfracture due to heat
      necrosis was not substantiated, because more empty osteocyte lacunae were
      associated with microfracture than drilling, probably due to shearing and
      crushing of adjacent bone. Drilling deeper to 6 mm versus 2 mm penetrated the
      epiphyseal scar in this model and led to greater subchondral hematoma. Our study
      revealed distinct differences between microfracture and drilling for acute
      subchondral bone structure and osteocyte necrosis. Additional ongoing studies
      suggest these differences significantly affect long-term cartilage repair
      outcome.

PMID- 19402151
TI  - VEGF serum concentrations in patients with long bone fractures: a comparison
      between impaired and normal fracture healing.
AB  - Vascular endothelial growth factor (VEGF) plays an important role in the bone
      repair process as a potent mediator of angiogenesis and it influences directly
      osteoblast differentiation. Inhibiting VEGF suppresses angiogenesis and callus
      mineralization in animals. However, no data exist so far on systemic expression
      of VEGF with regard to delayed or failed fracture healing in humans. One hundred
      fourteen patients with long bone fractures were included in the study. Serum
      samples were collected over a period of 6 months following a standardized time
      schedule. VEGF serum concentrations were measured. Patients were assigned to one
      of two groups according to their course of fracture healing. The first group
      contained 103 patients with physiological fracture healing. Eleven patients with
      delayed or nonunions formed the second group of the study. In addition, 33
      healthy volunteers served as controls. An increase of VEGF serum concentration
      within the first 2 weeks after fracture in both groups with a following decrease
      within 6 months after trauma was observed. Serum VEGF concentrations in patients
      with impaired fracture healing were higher compared to the patients with
      physiological healing during the entire observation period. However,
      statistically significant differences were not observed at any time point between
      both groups. VEGF concentrations in both groups were significantly higher than
      those in controls. The present results show significantly elevated serum
      concentrations of VEGF in patients after fracture of long bones especially at the
      initial healing phase, indicating the importance of VEGF in the process of
      fracture healing in humans.

PMID- 19402152
TI  - Evaluation of genome damage and its relation to oxidative stress induced by
      glyphosate in human lymphocytes in vitro.
AB  - In the present study we evaluated the genotoxic and oxidative potential of
      glyphosate on human lymphocytes at concentrations likely to be encountered in
      residential and occupational exposure. Testing was done with and without
      metabolic activation (S9). Ferric-reducing ability of plasma (FRAP),
      thiobarbituric acid reactive substances (TBARS) and the hOGG1 modified comet
      assay were used to measure glyphosate's oxidative potential and its impact on
      DNA. Genotoxicity was evaluated by alkaline comet and analysis of micronuclei and
      other nuclear instabilities applying centromere probes. The alkaline comet assay
      showed significantly increased tail length (20.39 microm) and intensity (2.19%)
      for 580 microg/ml, and increased tail intensity (1.88%) at 92.8 microg/ml,
      compared to control values of 18.15 mum for tail length and 1.14% for tail
      intensity. With S9, tail length was significantly increased for all
      concentrations tested: 3.5, 92.8, and 580 microg/ml. Using the hOGG1 comet assay,
      a significant increase in tail intensity was observed at 2.91 microg/ml with S9
      and 580 microg/ml without S9. Without S9, the frequency of micronuclei, nuclear
      buds and nucleoplasmic bridges slightly increased at concentrations 3.5 microg/ml
      and higher. The presence of S9 significantly elevated the frequency of nuclear
      instabilities only for 580 microg/ml. FRAP values slightly increased only at 580
      microg/ml regardless of metabolic activation, while TBARS values increased
      significantly. Since for any of the assays applied, no clear dose-dependent
      effect was observed, it indicates that glyphosate in concentrations relevant to
      human exposure do not pose significant health risk.

PMID- 19402154
TI  - Effects of zinc supplementation on the survival of patients who received
      concomitant chemotherapy and radiotherapy for advanced nasopharyngeal carcinoma:
      follow-up of a double-blind randomized study with subgroup analysis.
AB  - OBJECTIVES/HYPOTHESIS: Dietary zinc has been reported to have positive effects on
      treating carcinoma. This study examined the effects of zinc supplementation on
      the improved survival of patients with advanced nasopharyngeal carcinoma
      receiving concomitant chemotherapy and radiotherapy (CCRT). STUDY DESIGN: A
      double-blind, placebo-controlled clinical study with subgroup analysis. METHODS:
      Thirty-four patients with stages III and IV nasopharyngeal carcinoma were
      selected from a double-blind, placebo-controlled clinical study. All the patients
      were randomized to receive a standard dose (75 mg/day for 2 months) of zinc
      supplements or placebo, in conjunction with CCRT. The overall local recurrence,
      metastasis, and disease-free survivals were defined as the period between the
      time of first treatment to the time of death, local recurrence, or distant
      metastases occurred. RESULTS: Patients in the experimental group exhibited a
      higher 5-year overall local-free and disease-free survival rate than the patients
      in the placebo group (P = .044, P = .007, and P = .033, respectively). However,
      no significant differences were found between both patient groups for the 5-year
      metastases-free survival rate (P = .149). CONCLUSIONS: Zinc supplementation
      prescribed in conjunction with CCRT effects attenuating local tumor recurrence
      and improves the overall survival of patients with advanced nasopharyngeal
      carcinoma. The failure to reduce distant metastasis survival might have been
      related in part to the more advanced disease stages in our patients.

PMID- 19402153
TI  - Function of dynein in budding yeast: mitotic spindle positioning in a polarized
      cell.
AB  - Cytoplasmic dynein is a microtubule motor that powers minus-end-directed motility
      in a variety of biological settings. The budding yeast, Saccharomyces cerevisiae,
      has been a useful system for the study of dynein, due to its molecular genetics
      and cell biology capabilities, coupled with the conservation of dynein-pathway
      proteins. In this review we discuss how budding yeast use dynein to manipulate
      the position of the mitotic spindle and the nucleus during cell division, using
      cytoplasmic microtubules, and we describe our current understanding of the genes
      required for dynein function. Cell Motil. Cytoskeleton 2009. (c) 2009 Wiley-Liss,
      Inc.

PMID- 19402155
TI  - Dependence of DNA double strand break repair pathways on cell cycle phase in
      human lymphoblastoid cells.
AB  - DNA double-strand breaks (DSBs) are usually repaired by nonhomologous end-joining
      (NHEJ) or homologous recombination (HR). NHEJ is thought to be the predominant
      pathway operating in mammalian cells functioning in all phases of the cell cycle,
      while HR works in the late-S and G2 phases. However, relative contribution,
      competition, and dependence on cell cycle phases are not fully understood. We
      previously developed a system to trace the fate of DSBs in the human genome by
      introducing the homing endonuclease I-SceI site into the thymidine kinase (TK)
      gene of human lymphoblastoid TK6 cells. Here, we use this system to investigate
      the relative contribution of HR and NHEJ for repairing I-SceI-induced DSBs under
      various conditions. We used a novel transfection system, Amaxa nucleofector,
      which directly introduces the I-SceI expression vector into cell nuclei.
      Approximately 65% of transfected cells expressed the I-SceI enzyme and over 50%
      of the cells produced a single DSB in the genome. The relative contribution of
      NHEJ and HR for repairing the DSB was approximately 100:1 and did not change with
      transfection efficiency. Cotransfection with KU80-siRNA significantly diminished
      KU80 protein levels and decreased NHEJ activity, but did not increase HR. We also
      investigated HR and NHEJ in synchronized cells. The HR frequency was 2-3 times
      higher in late-S/G2 phases than in G1, whereas NHEJ was unaffected. Even in late
      S/G2 phases, NHEJ remained elevated relative to HR. Therefore, NHEJ is the major
      pathway for repairing endonuclease-induced DSBs in mammalian cells even in late
      S/G2 phase, and does not compete with HR.

PMID- 19402156
TI  - The role of paraoxonase polymorphisms in the induction of micronucleus in
      paraoxon-treated human lymphocytes.
AB  - Human paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme that
      has a role in the detoxification of organophosphorus compounds by hydrolyzing the
      bioactive oxons. PON1 polymorphims are responsible, at least in part, for the
      variation in the catalytic activity and expression of the enzyme and have been
      associated with susceptibility to organophosphorus pesticide toxicity, mainly
      neurotoxicity. The aim of this study was to determine whether paraoxon induced
      micronuclei and to examine the role of PON1 polymorphism in paraoxon's genotoxic
      potential. First, dose finding cytogenetic experiments were performed on
      lymphocyte cultures from three donors and a range of paraoxon concentration (1-25
      microM) were tested. In a second set of experiments, 5 microM paraoxon was added
      to blood cultures of 11 donors with two different PON1 haplotypes (PON T(
      108)M(55)Q(192) with low activity and haplotype PON C(-108)L(55) R(192) with high
      activity, referred to as PON1QQ and as PON1 RR, respectively). Because PON1 is
      present in blood, the effect of adding 5 microM paraoxon and 70 microl of
      autologous plasma to lymphocyte cultures also was examined. Paraoxon had no
      effect on cell viability, but caused a significant dose-dependent increase in MN
      frequency. The basal MN frequencies were similar on QQ and RR genotypes. A
      significant difference was observed in the MN frequency only in lymphocytes from
      individuals with the QQ genotype treated with 5 microM paraoxon and the
      autologous plasma did not modify these effects. The results obtained in this
      study suggest that PON1 genotype might have an important role in the
      identification of individuals at risk for cancer development due to occupational
      exposure to pesticides.

PMID- 19402157
TI  - The functional significance of centrosomes in mammalian meiosis, fertilization,
      development, nuclear transfer, and stem cell differentiation.
AB  - Centrosomes had been discovered in germ cells and germ cells continue to provide
      excellent but also challenging material in which to study complex centrosomal
      dynamics. The present review highlights the importance of centrosomes for meiotic
      spindle integrity and the susceptibility of meiotic spindle centrosomes to aging
      and drugs or toxic agents which may be associated with female infertility,
      aneuploidy, and developmental abnormalities. We discuss cell and molecular
      aspects of centrosomes during fertilization, a critical stage in which
      centrosomes play crucial roles in precisely organizing the sperm aster that
      allows apposition of male and female genomes followed by formation of the zygote
      aster that is important for the formation of the bipolar spindle apparatus during
      cell division. Development of an embryo involves sequential cell divisions in
      which centrosomes play a critical role in establishing asymmetry that allows
      differentiation of cells and targeted signal transductions for the developing
      embryo. Asymmetric centrosome dynamics are also critical for stem cell division
      to maintain one daughter cell as a stem cell while the other daughter cell
      undergoes centrosome growth in preparation for differentiation. This review also
      discusses the complex interactions of somatic cell centrosomes with the recipient
      oocyte in reconstructed (cloned) embryos in which centrosome remodeling is
      crucial to fulfill functions that are carried out by the zygote centrosome in
      fertilized eggs. We close our discussion with a look at centrosome dysfunctions
      and implications for male fertility and assisted reproduction.

PMID- 19402158
TI  - Effect of annatto on micronuclei induction by direct and indirect mutagens in
      HepG2 cells.
AB  - Annatto (AN), a natural food colorant rich in carotenoids, has been reported as
      being an effective antioxidant, but little is known about its potential
      chemopreventive properties. In this study, we evaluated the ability of AN to
      protect human hepatoma cells (HepG2) from micronucleus (MN) induction against
      three different mutagens: benzo(a)pyrene (B(a)P), doxorubicin (DXR), and methyl
      methanesulfonate (MMS). In an attempt to clarify the possible mechanism of
      antimutagenicity of AN, three protocols of treatment were applied (pretreatment;
      simultaneous treatment, and post-treatment with AN following treatment with the
      mutagens). Also, cells exposed only to AN were assayed for cytotoxicity and
      mutagenicity. A dosage up to 10 microg/ml of AN was devoid of mutagenic activity.
      Protective effects were seen on micronuclei induced by B(a)P and DXR using pre
      and simultaneous treatment, but AN had no significant effect on MN induction by
      MMS in any of the protocols. Our results also show that exposure of cells to
      concentrations of AN higher than 10 microg/ml decreased cell viability. Taken
      together, our findings indicate that AN presents antimutagenic activity in vitro,
      but its protective effect is dependent on the mutagen and on type of treatment
      suggesting its potential use as a chemopreventive agent.

PMID- 19402159
TI  - A rescuable folding defective Nav1.1 (SCN1A) sodium channel mutant causes GEFS+:
      common mechanism in Nav1.1 related epilepsies?
AB  - Mutations of voltage-gated Na(+) channels are the most common known cause of
      genetically determined epilepsy; Na(v)1.1 (SCN1A) is the most frequent target.
      They can cause both mild and severe forms, also in patients harboring the same
      mutation. We have recently characterized in a family with extreme phenotypes the
      first epileptogenic folding-defective Na(+) channel mutant (Na(v)1.1-M1841T),
      whose loss of function is attenuated by interactions with associated proteins and
      drugs. We hypothesized that in vivo variability of the interactions may modulate
      the functional effect and thus the phenotype (Rusconi et al., 2007). Here we
      characterize another Na(v)1.1 folding-defective mutant (Na(v)1.1-R1916G) that,
      however, has been identified in a GEFS+ family with relatively mild phenotypes.
      This novel mutant shows a number of specific characteristics, but, similarly to
      Na(v)1.1-M1841T, it can be rescued by interactions with associated proteins and
      drugs. Thus, loss of function caused by folding defects that can be attenuated by
      molecular interactions may be a common pathogenic mechanism for Na(v)1.1
      epileptogenic mutants. Folding defects can be present also in families showing
      only mild phenotypes in which, however, severe phenotypes could emerge within a
      permissive genetic background.

PMID- 19402160
TI  - BBS7 and TTC8 (BBS8) mutations play a minor role in the mutational load of Bardet
      Biedl syndrome in a multiethnic population.
AB  - Bardet Biedl syndrome is a genetically heterogeneous ciliopathy with fourteen
      genes currently identified. To date, mutations in BBS7 and TTC8 (BBS8) were
      reported in 4.2% and 2.8% of BBS families respectively. We sequenced the coding
      regions of BBS7 and TTC8 in 35 BBS families of diverse ancestral backgrounds. In
      addition, the role of putative modifier genes on phenotype severity; NXNL1 and
      MGC1203 c.430C>T, was assessed. Genotype-phenotype correlation was explored in
      patients with identified mutations. Four novel pathogenic BBS7 changes were
      identified in 2/35 families (5.7%). In one family with two affected individuals
      with BBS7 mutations, a more severe phenotype was observed in association with a
      third mutation in BBS4. The overall retinal phenotype appeared more severe than
      that seen in patients with BBS1 mutations. This study confirms the small role of
      BBS7 and TTC8 in the overall mutational load of BBS patients. The variability of
      the ocular phenotype observed, could not be explained by the putative modifier
      genes; NXNL1 and MGC1203 c.430C>T.

PMID- 19402167
TI  - Incidence and mortality rates for colorectal cancer in Puerto Rico and among
      Hispanics, non-Hispanic whites, and non-Hispanic blacks in the United States,
      1998-2002.
AB  - BACKGROUND: Colorectal cancer (CRC) is the second most commonly diagnosed cancer
      in Puerto Rico (PR). In the United States, the incidence and mortality rates of
      CRC have great variation by sex and race/ethnicity. Age-standardized incidence
      and mortality rates of CRC in PR were assessed and compared with the rates among
      US Hispanics (USH), non-Hispanic whites (NHW), and non-Hispanic blacks (NHB) in
      the United States for the period from 1998 through 2002. Incidence and mortality
      trends and relative differences among racial/ethnic groups by sex and age were
      determined. METHODS: Age-standardized rates using the world standard population
      (ASR[World]) were based on cancer incidence and mortality data from the PR
      Central Cancer Registry and from the National Cancer Institute's Surveillance,
      Epidemiology, and End Results Program using the direct method. The annual
      percentage changes (APC) and relative risks (RR) were calculated using Poisson
      regression models. RESULTS: During 1998 through 2002, the APC of CRC incidence
      and mortality increased for men in PR, whereas descending trends were observed
      for other racial/ethnic groups. Overall period rates indicated that, in both
      sexes, Puerto Ricans had CRC incidence and mortality rates similar to those for
      USH, but their rates were lower than those for NHW and NHB. However, Puerto Rican
      men and women ages 40 years to 59 years had the greatest risk of incidence and
      mortality compared with their USH counterparts. CONCLUSIONS: Areas of concern
      include the increasing trends of CRC in PR and the higher burden of the disease
      among young Puerto Ricans compared with the USH population. The authors concluded
      that further research should be performed to guide the design and implementation
      of CRC prevention and education programs in PR.

PMID- 19402168
TI  - Natural history, growth kinetics, and outcomes of untreated clinically localized
      renal tumors under active surveillance.
AB  - BACKGROUND: The growth kinetics of untreated solid organ malignancies are not
      defined. Radiographic active surveillance (AS) of renal tumors in patients unfit
      or unwilling to undergo intervention provides an opportunity to quantify the
      natural history of untreated localized tumors. The authors report the
      radiographic growth kinetics of renal neoplasms during a period of surveillance.
      METHODS: The authors identified patients with enhancing renal masses who were
      radiographically observed for at least 12 months. Clinical and pathological
      records were reviewed to determine tumor growth kinetics and clinical outcomes.
      Tumor growth kinetics were expressed in terms of absolute and relative linear and
      volumetric growth. RESULTS: The authors identified 172 renal tumors in 154
      patients under AS. Median tumor diameter and volume on presentation were 2.0 cm
      (mean, 2.5; range, 0.4-12.0) and 4.18 cm(3) (mean, 20.0; range, 0.033-904).
      Median duration of follow-up was 24 months (mean, 31; range, 12-156). A
      significant association between presenting tumor size and proportional growth was
      noted, with smaller tumors growing faster than larger tumors. Thirty-nine percent
      (68 of 173) of tumors underwent delayed intervention, and 84% (57 of 68) were
      pathologically malignant. Progression to metastatic disease was noted in 1.3% (2
      of 154) of patients. CONCLUSIONS: The authors demonstrated the association
      between a tumor's volume and subsequent growth, with smaller tumors exhibiting
      significantly faster volumetric growth than larger tumors, consistent with
      Gompertzian kinetics. Surveillance of localized renal tumors is associated with a
      low rate of disease progression in the intermediate term, and suggests potential
      overtreatment biases in select patients.

PMID- 19402169
TI  - Radiotherapy in adrenocortical carcinoma.
AB  - Adrenocortical carcinoma (ACC) is a rare malignancy, and patients with ACC have a
      poor prognosis. Even after radical surgery, up to 85% of patients develop
      recurrent disease. Systemic treatment options still have limited efficacy.
      Because the role of radiotherapy is not defined well and because ACC often is
      considered radioresistant, the authors reviewed the available data on
      radiotherapy for ACC. Original articles and reviews were identified using a
      PubMed search strategy that included the period up to July 2008. Ten articles
      were identified that covered radiotherapy in a total of 129 patients with ACC (64
      patients received postoperative irradiation, and 65 patients received palliative
      therapy for advanced disease). In addition, 26 patients were identified in the
      German ACC Registry who received palliative radiotherapy. Furthermore, patterns
      of failure after adjuvant radiotherapy were investigated, and the authors
      provided recommendations for patient selection, treatment planning, and treatment
      protocols. In an adjuvant setting, postoperative radiotherapy was able to prevent
      local recurrence in the majority of patients. In those with advanced disease, a
      response to radiotherapy was observed in 57% of patients who received palliative
      radiotherapy. Therefore, the authors concluded that radiotherapy may play an
      important role in the care of patients with ACC. Until better evidence is
      available, the authors recommended the following approach: Adjuvant radiotherapy
      to the tumor bed should be considered in patients at high risk for local
      recurrence (eg, incomplete/R1 resection); a total dose of >40 grays (Gy) with
      single fractions of 1.8 Gy to 2 Gy should be administered (including a boost
      volume to reach from 50 Gy to 60 Gy in individual patients); and radiotherapy in
      a palliative setting may be used for symptomatic metastases to bone, brain, or
      vena cava obstruction. With state-of-the-art technology, acute and long-term
      toxicities mostly were mild to moderate. However, the authors concluded that
      prospective investigations would be required to fully define the therapeutic
      potential of this important treatment option.

PMID- 19402170
TI  - Treatment of fludarabine-refractory chronic lymphocytic leukemia.
AB  - The development of resistance to purine analogs defines a poor-risk subset of
      patients with chronic lymphocytic leukemia (CLL). Although in recent years
      chemoimmunotherapeutic combinations such as fludarabine, cyclophosphamide, and
      rituximab have induced response rates of 95% in previously untreated patients and
      increased the rates of failure-free survival, CLL remains incurable for many
      patients because of a lack of disease response or the development of
      refractoriness to fludarabine. Fludarabine-refractory disease is defined as CLL
      that does not respond to fludarabine or that recurs within 6 months of treatment
      with a fludarabine-containing regimen. The natural course of the disease is
      associated with poor survival. Salvage therapeutic strategies include alemtuzumab
      containing regimens, targeted agents, and allogeneic stem cell transplantation.
      Single-agent alemtuzumab induces response in up to 40% of patients with
      fludarabine-refractory CLL, but responses are not durable, and the median
      survival is approximately 1 to 2 years. Alemtuzumab is also combined with
      fludarabine, cyclophosphamide, and/or rituximab, and other agents such as
      lenalidomide and flavopiridol, as well as targeted agents, and used in
      fludarabine-refractory CLL. Cumulative evidence suggests that allogeneic stem
      cell transplantation is an efficacious therapeutic strategy for patients who do
      not respond to fludarabine or who develop disease recurrence within 12 months
      after purine analog treatment. In conclusion, chemoimmunotherapy regimens that
      include alemtuzumab and/or rituximab and allogeneic stem cell transplantation
      improve the prognosis of this disease, but there is a continued need for novel,
      more effective therapies.

PMID- 19402171
TI  - Dasatinib early intervention after cytogenetic or hematologic resistance to
      imatinib in patients with chronic myeloid leukemia.
AB  - BACKGROUND: Although many patients with chronic myeloid leukemia (CML) respond
      well to imatinib therapy, a significant proportion loses their initial response.
      Loss of response on imatinib is often because of BCR-ABL mutations. Dasatinib is
      a 325-fold more potent inhibitor of Bcr-Abl than imatinib and has been associated
      with high rates of durable responses in patients with CML in chronic phase (CP)
      after imatinib failure. METHODS: To determine the optimal time for initiating
      dasatinib after loss of response on imatinib, data from dasatinib trials in CML
      CP were analyzed. Patients were grouped according to whether they received early
      intervention with dasatinib (ie, after cytogenetic recurrence on imatinib),
      rather than after both cytogenetic and hematologic recurrence. RESULTS: Overall,
      72% of patients who received dasatinib after loss of a major cytogenetic response
      (MCyR) on imatinib achieved a complete cytogenetic response (CCyR) compared with
      42% of patients who were treated after loss of both MCyR and complete hematologic
      response (CHR). Event-free survival (EFS) also was higher after earlier dasatinib
      treatment (24-month EFS rates: 89% after loss of MCyR on imatinib vs 29% after
      loss of both MCyR and CHR). Among patients who were treated after loss of CHR on
      imatinib with no prior MCyR, 26% achieved a CCyR with dasatinib, and the 24-month
      EFS rate was 64%. In all 3 groups, CCyR rates were similar in patients with or
      without pre-existing BCR-ABL mutations. CONCLUSIONS: The results of the current
      study suggested that optimal outcomes are achieved when dasatinib is administered
      early after imatinib resistance.

PMID- 19402173
TI  - Clinical outcomes of molecularly confirmed clear cell sarcoma from a single
      institution and in comparison with data from the Surveillance, Epidemiology, and
      End Results registry.
AB  - BACKGROUND: The authors compared disease-specific survival (DSS) in stage
      specific subgroups of patients with clear cell sarcoma, including those with
      lymph node metastases (N1M0) and those with distant metastases (N0M1). METHODS:
      Clinical data regarding soft tissue sarcoma patients were obtained from The
      University of Texas M. D. Anderson Cancer Center (MDACC) (1980-2007) and the
      Surveillance, Epidemiology, and End Results (SEER) registry (1988-2004). When
      possible, clear cell sarcoma diagnoses were confirmed using fluorescence in situ
      hybridization or reverse-transcription polymerase chain reaction. Kaplan-Meier
      estimates were used to calculate DSS, and Cox multivariate analysis was performed
      to identify prognostic factors. RESULTS: Fifty-two patients at MDACC and 130 SEER
      patients were diagnosed with clear cell sarcoma. Five-year DSS for the MDACC and
      SEER cohorts were 67% and 62%, respectively. Patients with N1M0 and N0M1 disease
      demonstrated significant differences in 5-year DSS: 74% versus 14% at MDACC (P =
      .014) and 52% versus 0% in SEER (P = .014). After adjustment, the hazards ratio
      (HR) for dying was 2.79 for N1M0 disease (95% confidence interval [95% CI], 1.32
      5.91) and 11.37 (95% CI, 5.19-24.91) for N0M1 disease compared with stage II
      disease (P < .001). Non-Caucasian ethnicity (HR, 3.99; 95% CI, 2.27-6.99 [P <
      .001]) and truncal tumor site (HR, 2.41; 95% CI, 1.15-5.05 [P = .02]) were also
      found to be predictors of decreased DSS. CONCLUSIONS: The findings of the current
      study suggest that patients with N1M0 clear cell sarcoma have 5-year DSS that is
      more similar to that of patients with stage III than stage IV soft tissue
      sarcoma.

PMID- 19402172
TI  - Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults
      with recurrent malignant glioma.
AB  - BACKGROUND: The current study was a phase 1 clinical trial conducted with
      patients who had recurrent or progressive malignant glioma (MG). The trial was
      designed to determine the maximum tolerated dose (MTD) and toxicity of irinotecan
      (CPT-11) when administered with temozolomide (TMZ) and O(6)-benzylguanine (O(6)
      BG). METHODS: All 3 drugs, CPT-11, TMZ, and O(6)-BG, were administered on Day 1
      of a 21-day treatment. First, patients were treated with a 1-hour bolus infusion
      of O(6)-BG at a dose of 120 mg/m(2) followed immediately by a 48-hour continuous
      infusion of O(6)-BG at a dose of 30 mg/m(2)/d. Second, within 60 minutes of the
      end of the 1-hour bolus infusion of O(6)-BG, TMZ was administered orally at a
      dose of 355 mg/m(2). Third, 1 hour after administration of TMZ, CPT-11 was
      infused over 90 minutes. Patients were accrued to 1 of 2 strata based on CYP3A1-
      and CYP3A4-inducing antiepileptic drug (EIAED) use; dose escalation was conducted
      independently within these strata. RESULTS: Fifty-five patients were enrolled. In
      both strata, the dose-limiting toxicities were hematologic and included grade 4
      neutropenia, febrile neutropenia, leukopenia, and/or thrombocytopenia. For
      Stratum 1 (EIAEDs), when TMZ was administered at a dose of 355 mg/m(2), the MTD
      of CPT-11 was determined to be 120 mg/m(2). In contrast, for Stratum 2 (no
      EIAEDs), when TMZ was administered at a dose of 200 mg/m(2), the MTD of CPT-11
      was determined to be 80 mg/m(2). CONCLUSIONS: The authors believe that the
      results of the current study provide the foundation for a phase 2 trial of O(6)
      BG in combination with CPT-11 and TMZ in patients with MG.

PMID- 19402174
TI  - Excision is indicated for intraductal papilloma of the breast diagnosed on core
      needle biopsy.
AB  - BACKGROUND: Although it has been accepted that intraductal papillomas with atypia
      or malignancy diagnosed on core needle biopsy require surgical excision, the
      management of pure intraductal papillomas has been controversial. Because some
      series reported a small but definite incidence of atypia or malignancy, whereas
      others claimed that radiologic follow-up was adequate, this study evaluated
      results of excision of all pure intraductal papillomas diagnosed on core needle
      biopsy at this institution. METHODS: By using computerized pathology files from
      January of 2000 to December of 2004, 200 cases of intraductal papillomas on core
      needle biopsy were identified. Information regarding excision was available in
      104 cases. All specimens were reviewed to confirm both the diagnoses as well as
      the presence of biopsy site changes in excision specimens, and the findings were
      correlated with radiologic data. RESULTS: The age of the patients ranged from 25
      to 82 years (mean, 55.5). The diagnoses on excision were as follows: intraductal
      papillomas = 71 cases (68.3%), no residual intraductal papillomas = 16 (15.3%),
      atypical duct hyperplasia = 8 (7.7%), ductal carcinoma in situ = 6 (5.8%), and
      invasive carcinoma = 3 (2.9%). In cases with atypia or malignancy, these findings
      were adjacent to but not in the biopsy site. In cases with atypical duct
      hyperplasia or ductal carcinoma in situ, a spectrum of histologic changes ranging
      from florid to atypical duct hyperplasia (14 cases), to ductal carcinoma in situ
      (6 cases) were present, all involving intraductal papillomas. CONCLUSIONS: The
      upstage rate of pure intraductal papillomas on core needle biopsy to atypia or
      malignancy on excision was 16.4%. Because of sampling error and the close
      proximity of atypia or malignancy to the intraductal papillomas (suggesting
      precancerous potential), excision was recommended of these lesions diagnosed on
      core needle biopsy. Close radiologic-pathologic correlation was important in the
      evaluation of these lesions.

PMID- 19402176
TI  - Centriole assembly in CHO cells expressing Plk4/SAS6/SAS4 is similar to
      centriogenesis in ciliated epithelial cells.
AB  - Centriole assembly is initiated by Plk4, a Polo-like kinase 4, which causes the
      recruitment of downstream regulators, such as SAS6 and SAS4, to a nascent
      centriole. Simultaneous expression of Plk4, SAS6 and SAS4 in CHO cells resulted
      in the formation of massive fibrogranular aggregates of various sizes and shapes.
      These aggregates were surrounded by dense particles of about 70 nm in diameter,
      similar to the centriolar satellite that has been observed around the centrosome
      in normal cycling cells. Within the fibrillar material, ring-like structures
      appeared and eventually differentiated into centrioles by association with short
      microtubule bundles. Centrioles were also assembled around a parent centriole in
      a cluster, a configuration that has been described as a "flower structure"
      formation [Kleylein-Sohn et al.,2007]. This pattern of centriole duplication is
      reminiscent of the arrangement of new centrioles induced in normal ciliated
      trachea/oviduct cells by the centriole-dependent pathway, which was reported
      several decades ago [Sorokin,1968; Anderson and Brenner,1971; Dirksen,1971].
      Prior to the production of hundreds of centrioles, these differentiating
      epithelial cells were also shown to induce a dense filamentous material similar
      to that detected in transfected CHO cells. These results suggest a common
      mechanism of centriole assembly regulated by Plk4 in both transfected cycling
      cells and normal ciliated epithelial cells undergoing differentiation. Cell
      Motil. Cytoskeleton 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19402175
TI  - Prognostic factors differ by tumor stage for small cell lung cancer: a pooled
      analysis of North Central Cancer Treatment Group trials.
AB  - BACKGROUND: An analysis of 14 small cell lung cancer (SCLC) trials was performed
      to improve the current understanding of potential prognostic factors for overall
      survival (OS) and progression-free survival (PFS) in groups of patients with
      limited-stage disease SCLC (LD-SCLC) and extensive-stage disease SCLC (ED-SCLC)
      separately. METHODS: Data on 688 patients with LD-SCLC and 910 patients with ED
      SCLC were included. Clinical and laboratory factors were tested for their
      prognostic significance using Cox regression models that were stratified by
      protocol. Recursive partitioning and amalgamation (RPA) analyses were used to
      identify prognostic subgroups. RESULTS: Poorer performance status (PS) led to
      worse OS and PFS in the ED-SCLC group but not in the LD-SCLC group. The
      prognostic impact of PS was strong for men but weak for women in the ED-SCLC
      group (interaction P value <.012 for OS and PFS). Other negative prognostic
      factors included increased age and men for the LD-SCLC group and increased age,
      men, increased number of metastatic sites at baseline, and increased creatinine
      levels for the ED-SCLC group. In patients with the ED-SCLC, RPA analyses
      identified 5 subgroups with different prognosis based on baseline PS, creatinine
      levels, sex, and the number of metastatic sites. CONCLUSIONS: The current pooled
      analysis identified baseline creatinine levels and the number of metastatic sites
      as important prognostic factors in patients with ED-SCLC in addition to the well
      established factors of sex, age, and PS. There was a significant interaction
      between sex and PS within the ED-SCLC group, suggesting that PS is highly
      prognostic in men but has no significant impact in women. Within the LD-SCLC
      group, only age and sex were identified as important prognostic factors. RPA
      analyses confirmed many of these findings.

PMID- 19402177
TI  - Quantitative separation of oxytocin, norfloxacin and diclofenac sodium in milk
      samples using capillary electrophoresis.
AB  - A simple, sensitive and rapid method has been developed for simultaneous
      separation and quantification of three different drugs: oxytocin (OT),
      norfloxacin (NOR) and diclofenac (DIC) sodium in milk samples using capillary
      electrophoresis (CE) with UV detection at 220 nm. Factors affecting the
      separation were pH, concentration of buffer and applied voltage. Separation was
      obtained in less than 9 min with sodium tetraborate buffer of pH 10.0 and applied
      voltage 30 kV. The separation was carried out from uncoated fused silica
      capillary with effective length of 50 cm with 75 microm i.d. The carrier
      electrolyte gave reproducible separation with calibration plots linear over 0.15
      4.0 microg/mL for OT, 5-1000 microg/mL for NOR and 3-125 microg/mL for DIC. The
      lower limits of detection (LOD) were found to be 50 ng/mL for OT, and 1 microg/mL
      for NOR and DIC. The method was validated for the analysis of drugs in milk
      samples and pharmaceutical preparations with recovery of drugs within the range
      96-100% with RSD 0.9-2.8%.

PMID- 19402178
TI  - Bioanalytical assay validation parameters re-visited: perspectives on stability
      studies.
AB  - Bioanalytical assay validation for plethora of parameters is considered vital for
      the reliable and accurate generation of raw analytical data used for
      pharmacokinetic characterization of analytes. Although the validation parameters
      have been widely accepted, the intent of this communication is to provide some
      perspectives on the commonly followed approaches for stability studies (i.e.
      freeze-thaw and long-term freezer stability studies). The proposed discussion is
      intended to stimulate the thinking process to cut down on the extra work and/or
      maximize the efficiency in the bioanalytical work. Additionally, the availability
      of new emerging technological know-hows and latest nuances in the field should
      provide the necessary impetus to innovate and articulate strategies for smart
      assay development/validation work for analytes.

PMID- 19402179
TI  - Analysis of hydroxyl radical-induced oxidation process of glucagon by reversed
      phase HPLC and ESI-MS/MS.
AB  - Structural modification of a polypeptide hormone, glucagon, by a hydroxyl radical
      in vitro was investigated by reversed-phase high-performance liquid
      chromatography (RP-HPLC), and the oxidized site of glucagon was detected by
      electrospray ionization tandem mass spectrometry (ESI-MS/MS). It was shown that
      (27)methionine (Met) was oxidized to (27)Met sulfoxide by hydroxyl radical, and
      the production rate of (27)Met sulfoxide was faster than that by hydrogen
      peroxide. In addition, production of (27)Met sulfoxide enantiomer was confirmed
      by RP-HPLC analysis. cAMP production in a HepG2 cell induced by (27)Met sulfoxide
      glucagon was reduced to approximately 75% as compared with that induced by the
      native form of glucagon.

PMID- 19402180
TI  - Simultaneous determination of five coumarins in Angelicae dahuricae Radix by
      HPLC/UV and LC-ESI-MS/MS.
AB  - Rapid, simple and reliable HPLC/UV and LC-ESI-MS/MS methods for the simultaneous
      determination of five active coumarins of Angelicae dahuricae Radix,
      byakangelicol (1), oxypeucedanin (2), imperatorin (3), phellopterin (4) and
      isoimperatorin (5) were developed and validated. The separation condition for
      HPLC/UV was optimized using a Develosil RPAQUEOUS C(30) column using 70%
      acetonitrile in water as the mobile phase. This HPLC/UV method was successful for
      providing the baseline separation of the five coumarins with no interfering peaks
      detected in the 70% ethanol extract of Angelicae dahuricae Radix. The specific
      determination of the five coumarins was also accomplished by a triple quadrupole
      tandem mass spectrometer equipped with an electrospray ionization source (LC-ESI
      MS/MS). Multiple reaction monitoring (MRM) in the positive mode was used to
      enhance the selectivity of detection. The LC-ESI-MS/MS methods were successfully
      applied for the determination of the five major coumarins in Angelicae dahuricae
      Radix. These HPLC/UV and LC-ESI-MS/MS methods were validated in terms of
      recovery, linearity, accuracy and precision (intra- and inter-day validation).
      Taken together, the shorter analysis time involved makes these HPLC/UV and LC-ESI
      MS/MS methods valuable for the commercial quality control of Angelicae dahuricae
      Radix extracts and its pharmaceutical preparations.

PMID- 19402181
TI  - Establishment of liquid chromatography/mass spectrometry for determination of
      bicyclol in rat single-pass intestinal perfusion.
AB  - A simple, rapid and sensitive method was developed for determination of bicyclol,
      a new synthetic anti-hepatitis drug, in rat plasma from the mesenteric vein using
      a high-performance liquid chromatography system coupled to a positive ion
      electrospray-mass spectrometric analysis. Bicyclol and internal standard
      (biphenyldicarboxylate, DDB) were isolated from plasma by liquid-liquid
      extraction, then separated on a Zorbax SB-C(18) column (3.5 microm, 2.1 x 100 mm)
      with mobile phase of methanol-water (60:40, v/v) at a flow rate of 0.2 mL/min.
      Detection was performed on a Trap XCT mass spectrometer equipped with an
      electrospray ionization (ESI) source operated in selected ion monitoring mode.
      Positive ion ESI was used to form sodium adduct molecular ions at m/z 413 for
      bicyclol and m/z 441 for DDB, respectively. A linear detection response was
      obtained for bicyclol ranging from 3.3 to 333.3 ng/mL and the lower limit of
      quantitation was 3.3 ng/mL. The coefficients of variation for intra- and inter
      day precisions were 1.1-7.7 and 2.0-6.6%, respectively. The percentage of
      absolute recovery of bicyclol was 85.3-94.6%. All analytes proved to be stable
      during all sample storage, preparation and analytic procedures. The method was
      successfully applied to determine the plasma concentration of bicyclol in
      mesenteric vein after intestinal perfusion.

PMID- 19402183
TI  - Development and reproducibility of a novel high-performance liquid-chromatography
      monolithic column method for the detection and quantification of trans-indolyl-3
      acryloylglycine in human urine.
AB  - Elevated levels of trans-indolyl-3-acryloylglycine (IAcrGly) have been reported
      in the urine of people with various conditions including pervasive developmental
      disorders (PDDs) such as autism and Asperger syndrome. Reversed-phase high
      performance liquid chromatography with ultra-violet detection using traditional
      particle silica-based columns subsequent to solid-phase extraction (SPE) has been
      the preferred assay method; requiring long analytical run times, high flow rates
      and high solvent usage. Recent developments in monolithic HPLC column technology
      facilitated the development of a novel analytical method, for the detection and
      quantification of urinary IAcrGly. The revised method eliminates the requirement
      for SPE pre-treatment, reduces sample run-time and decreases solvent volumes.
      Five urine samples from people diagnosed with PDD were run in quadruplicate to
      test the intra- and inter-day reliability of the new method based on retention
      time, peak area and peak height for IAcrGly. Detection was by UV with IAcrGly
      confirmation by MS/MS-MS. Relative standard deviations showed significant
      improvement with the new method for all parameters. The new method represents a
      major advancement in the detection and quantification of IAcrGly by reducing time
      and cost of analysis whilst improving detection limits and reproducibility.

PMID- 19402182
TI  - Assay of free captopril in human plasma as monobromobimane derivative, using
      RPLC/(+)ESI/MS/MS: validation aspects and bioequivalence evaluation.
AB  - A sensitive method for determination of free captopril as monobromobimane
      derivative in plasma samples is discussed. The internal standard (IS) was 5
      methoxy-1H-benzimidazole-2-thiol. Derivatization with monobromobimane immediately
      after blood collection and plasma preparation prevents oxidation of captopril to
      the corresponding disulfide compound and enhances the ionization yield.
      Consequently, derivatization enhances sample stability and detection sensitivity.
      Addition of the internal standard was made immediately after plasma preparation.
      The internal standard was also derivatized by monobromobimane, as it contains a
      thiol functional group. Preparation of plasma samples containing captopril and IS
      derivatives was based upon protein precipitation through addition of
      acetonitrile, in a volumetric ratio 1:2. The reversed-phase liquid
      chromatographic separation was achieved on a rapid resolution cartridge Zorbax SB
      C(18), monitored through positive electrospray ionization and tandem MS detection
      using the multiple-reaction monitoring mode. Transitions were 408-362 amu for the
      captopril derivative and 371-260 amu for the internal standard derivative. The
      kinetics of captopril oxidation to the corresponding disulfide compound in plasma
      matrix was also studied using the proposed method. A linear log-log calibration
      was obtained over the concentration interval 2.5-750 ng/mL. A low limit of
      quantitation in the 2.5 ng/mL range was obtained. The analytical method was fully
      validated and successfully applied in a three-way, three-period, single-dose (50
      mg), block-randomized bioequivalence study for two pharmaceutical formulations
      (captopril LPH 25 and 50 mg) against the comparator Capoten 50 mg.

PMID- 19402184
TI  - Ultrasonic extraction and HPLC determination of anthraquinones, aloe-emodine,
      emodine, rheine, chrysophanol and physcione, in roots of Polygoni multiflori.
AB  - INTRODUCTION: Polygoni multiflori, one of traditional Chinese herbal medicines
      for the treatment of various diseases commonly associated with aging, is known to
      contain active anthraquinone ingredients. However, the content of the
      anthraquinones varies among P. multiflori samples with collection season and
      sites. Thus, simple, reliable and accurate analytical methods for determining of
      anthraquinones in P. multiflori products are needed for the quality control and
      pharmacological studies. OBJECTIVE: To develop an HPLC method for the
      simultaneous determination of five anthraquinones, aloe-emodine, rheine, emodine,
      chrysophanol and physcione, in the roots of P. multiflori. METHODOLOGY:
      Anthraquinones were extracted from the roots of P. multiflori using aqueous
      alcohol solutions or hot water under ultrasonication. Separation and quantitation
      of anthraquinones was accomplished using a reversed-phase C18 column with the
      mobile phase of methanol-water-phosphoric acid (600:400:1), and the detection
      wavelength of 254 nm. RESULTS: Seventy per cent aqueous ethanol showed the
      highest extraction efficiency for anthraquinones from roots of P. multiflori when
      compared with four other extraction solvents tested. All calibration curves were
      linear over the concentration range tested with the square of correlation
      coefficients >0.999. The detection limits (S/N = 3) were 0.89, 1.1, 1.6, 1.7 and
      2.0 ng for chrysophanol, aloe-emodine, rheine, emodine and physcione,
      respectively. Emodine and physcione were found in the samples tested at
      concentrations of 0.341 and 0.197 mg/g, respectively. CONCLUSION: The described
      HPLC methods are simple, accurate and selective techniques for separation and
      quantification of anthraquinones in roots of P. multiflori and other plant
      samples.

PMID- 19402185
TI  - Identification of chrysanthenyl esters from the essential oil of Anthemis
      maritima L. investigated by GC/RI, GC-MS (EI and CI) and 13C-NMR spectroscopy:
      chemical composition and variability.
AB  - INTRODUCTION: Anthemis maritima L. (Asteraceae) is a wild plant growing in
      Corsica and Sardinia. No previous studies of the chemical composition of A.
      maritima essential oil have been found. The oil contains two series of cis- and
      trans-chrysanthenyl esters for which the MS data are not present in available
      libraries and the 13C-NMR data are not reported in the literature. The
      determination of these compounds is a challenging problem since some of these
      esters are present in low concentrations and they exhibit very similar EI-MS.
      OBJECTIVE: To develop comprehensive strategies involving integrated techniques
      including CC, GC/RI, GC-MS (EI and CI), 1H- and 13C-NMR and hemi-synthesis for
      the identification of both series of chrysanthenyl esters in A. maritima oils.
      METHODOLOGY: Seventeen oil samples were prepared by hydrodistillation. A fine
      analysis of a pool of Corsican oils was conducted after repeated CC. A selected
      Sardinian oil was used as source of product for the hemi-synthesis of
      chrysanthenyl esters. The identification of these compounds was based on joint
      information from GC-MS (EI and CI), 13C-NMR and hemi-synthesis. RESULTS:
      Integrated analysis of Corsican and Sardinian oils allowed the identification of
      124 components accounting for 83.3-91.6% of the total oil. With the aid of
      principal component analysis, oil samples could be divided in two groups. Among
      16 chrysanthenyl esters identified, 12 were laboratory-synthesised and their 13C
      NMR data are reported for the first time. CONCLUSIONS: The study illustrates the
      contribution of integrated techniques for the characterisation of unusual
      essential oils.

PMID- 19402186
TI  - The analysis of heavy metals in Chinese herbal medicine by flow injection-mercury
      hydride system and graphite furnace atomic absorption spectrometry.
AB  - INTRODUCTION: Simple and robust atomic absorption spectrometry (AAS) analytical
      methods were developed to determine the contents of arsenic (As), lead (Pb) and
      mercury (Hg) contained in Chinese herbal medicine products or Chinese proprietary
      medicine. OBJECTIVE: To develop AAS analytical methods to determine the contents
      of the toxic heavy metals in herbal medicine, and thus monitor them according to
      the regulated content limits to ensure the quality and safety of herbal products.
      METHODOLOGY: A flow injection-mercury hydride system technique was used for the
      quantitation of As and Hg, and a graphite furnace technique was used for the
      analysis of Pb. Limits of detection (LOD) for the three toxic heavy metals were
      found to be 0.3 ppb for As, 0.1 ppb for Pb and 0.5 ppb for Hg. Eight samples of
      'Yin Qiao Jie Du' tablets available on the market were selected as the model
      herbal medicine for analysis. CONCLUSION: The developed analytical methods are
      sensitive enough to detect these heavy metals to meet regulated guidelines. No
      trace amounts of Hg were found in the test samples due to the fact that the Hg
      level is less than the LOD. However, variable amounts of As (135.0-5349.3 ppb)
      and Pb (22.5-968.3 ppb) were found in all products.

PMID- 19402187
TI  - A simple isocratic HPLC method for the simultaneous determination of curcuminoids
      in commercial turmeric extracts.
AB  - INTRODUCTION: Turmeric (Curcuma longa) extracts contain three curcuminoids
      (curcumin, desmethoxycurcumin and bisdesmethoxycurcumin) as major bioactive
      substances. Previously reported HPLC-UV methods for the determination of
      curcuminoids have several disadvantages, including unsatisfactory separation
      times, poor resolution and/or complicated solvent mixtures with gradient elution.
      OBJECTIVE: To develop a simple isocratic HPLC-UV method for the simultaneous
      determination of individual curcuminoids for the quality control of turmeric
      extracts. METHODOLOGY: The sample was prepared by dissolving the extract in
      acetonitrile and subsequently diluting with 50% acetonitrile. This solution was
      analysed by reverse-phase chromatography on an Alltima C(18) column with
      isocratic elution of acetonitrile and 2% v/v acetic acid (40:60, v/v) at a flow
      rate of 2.0 mL/min, a column temperature of 33 degrees C, and UV detection at 425
      nm. The method was validated and applied for quantification of individual
      curcuminoids in commercial turmeric extracts. RESULTS: The method allowed
      simultaneous determination of curcumin, desmethoxycurcumin and
      bisdesmethoxycurcumin in the concentration ranges of 10-60, 4-24 and 0.5-3.0
      microg/mL, respectively. The limits of detection and quantification were,
      respectively, 0.90 and 2.73 microg/mL for curcumin, 0.84 and 2.53 microg/mL for
      desmethoxycurcumin and 0.08 and 0.23 microg/mL for bisdesmethoxycurcumin, and the
      percentage recoveries were, respectively, 99.16-101.75 (%RSD < or = 1.11%), 99.50
      101.01 (%RSD < or = 1.74%) and 99.67-101.92 (RSD < or = 1.31%). CONCLUSION: The
      method was found to be simple, accurate and precise and is recommended for
      routine quality control analysis of turmeric extracts containing the three
      curcuminoid compounds as the main principles in the herb.

PMID- 19402188
TI  - Comparison of the phenolic component profiles of skullcap (Scutellaria
      lateriflora) and germander (Teucrium canadense and T. chamaedrys), a potentially
      hepatotoxic adulterant.
AB  - INTRODUCTION: Scutellaria lateriflora, commonly known as skullcap, is used as an
      ingredient in numerous herbal products. Unfortunately, it has occasionally been
      adulterated with Teucrium canadense or T. chamaedrys, commonly known as
      germander, which contains potentially hepatotoxic diterpenes. Chromatographic
      profiles of the phenolic components provide a means of distinguishing between
      these plants and enhancing public safety. OBJECTIVE: To develop a chromatographic
      method for the identification of Scutellaria lateriflora and two Teucrium species
      and to quantify the latter as adulterants. METHODOLOGY: Samples were extracted
      with aqueous methanol and the extracts were analysed using a standardised LC-DAD
      ESI/MS profiling method to obtain their phenolic profiles. RESULTS: Skullcap
      contained primarily flavonoids, while the major phenolic components of the two
      Teucrium species were the phenylethanoids, verbascoside and teucrioside. Using
      the phenylethanoids as markers, it was possible to clearly distinguish between
      the two genus and to determine 5% Teucrium mixed with Scutellaria using either
      ultraviolet absorption spectrometry or mass spectrometry in the total ion count
      mode. Using MS in the selective ion monitoring (SIM) mode, 1% Teucrium could be
      measured. CONCLUSIONS: This study showed that chromatographic profiling was able
      to identify Scutellaria and Teucrium, separately and when mixed together.

PMID- 19402190
TI  - Randomized clinical trial of anal fistula plug versus endorectal advancement flap
      for the treatment of high cryptoglandular fistula in ano.
AB  - BACKGROUND: The aim of this randomized study was to compare the results of anal
      fistula plug and endorectal advancement flap in the treatment of high fistula in
      ano of cryptoglandular origin. METHODS: Consecutive patients with high trans
      sphincteric fistula in ano of cryptoglandular aetiology were randomized to
      treatment with either an anal fistula plug or endorectal advancement flap.
      Patients agreed to participate in a follow-up programme, which included scheduled
      visits at 2, 4, 8, 12 and 24 weeks and at 1 year after surgery. The primary
      endpoint was effectiveness in fistula healing. Recurrence was defined as the
      presence of an abscess arising in the same area, or obvious evidence of
      fistulation. RESULTS: A large number of recurrences in the fistula plug group led
      to premature closure of the trial. After 1 year, fistula recurrence was noted in
      12 of 15 patients treated with an anal fistula plug compared with two of 16
      treated with an endorectal advancement flap (relative risk 6.40 (95 per cent
      confidence interval 1.70 to 23.97); P < 0.001). CONCLUSION: Contrary to other
      published studies, an anal fistula plug was associated with a low rate of fistula
      healing, particularly in patients with a history of fistula surgery.

PMID- 19402189
TI  - Antioxidant diterpenoids from the roots of Salvia barrelieri.
AB  - INTRODUCTION: The phytochemical and biological studies carried out on Salvia
      species showed that their extracts and constituents have various biological
      activities. OBJECTIVE: The aim of this study was the isolation of diterpenoids
      from the roots of Salvia barrelieri Ettling and the determination of the
      antioxidant activity. METHODOLOGY: Chromatographic methods were used for
      fractionation and isolation, respectively. Structure elucidation was established
      by spectroscopic methods. Five antioxidant assays were performed. RESULTS: Three
      new abietane diterpenoids barreliol, royleanone 12-methyl ether and 7-epi
      salviviridinol, and six known diterpenoids, with a known dammarane triterpenoid,
      pyxinol were isolated. The absolute stereochemistry of pyxinol was confirmed by X
      ray analysis. CONCLUSION: Taxodione exhibited the highest antioxidant activity
      among the tested compounds.

PMID- 19402191
TI  - Randomized clinical trial of efficacy and costs of three dissection devices in
      liver resection.
AB  - BACKGROUND: In recent decades a variety of instruments for liver dissection has
      become available. This randomized controlled trial analysed the efficacy and
      costs of three different liver dissection devices. METHODS: Ninety-six patients
      without cirrhosis undergoing liver resection were randomized to either ultrasonic
      dissection, waterjet dissection or dissecting sealer (32 in each group). Patients
      were unaware of the device used. The primary endpoint was dissection speed.
      Secondary endpoints were intraoperative blood loss, morbidity and mortality, and
      costs of dissection devices, staplers and haemostatic agents. RESULTS: Dissection
      was slower with the dissecting sealer (P = 0.004 versus waterjet dissector). The
      difference was more pronounced for extended resections (mean(s.e.m.) 1.62(0.36)
      cm(2)/min versus 3.42(0.53) and 3.63(0.51) cm(2)/min for ultrasonic and water
      dissectors respectively; P = 0.037). Costs were significantly higher for the
      dissecting sealer when atypical or segmental resections were performed. Four
      patients died after extended resections; postoperative complications did not
      differ between groups. CONCLUSION: The dissecting sealer is slower than the
      ultrasonic dissector or water dissector. The three devices are equally safe in
      terms of blood loss, transfusions and postoperative complications. Ultrasonic and
      water dissectors might be more favourable economically than the dissecting
      sealer. REGISTRATION NUMBER: ISRCTN52294555 (http://www.controlled-trials.com).

PMID- 19402192
TI  - Deep vein thrombosis.  Preventing blood clots in the legs.

PMID- 19402193
TI  - Forget about ginkgo supplements to aid memory.

PMID- 19402194
TI  - Treating anxiety.  Take back your life.

PMID- 19402195
TI  - Is it possible to whiten teeth too much?  I've seen people who have almost
      freakishly white teeth.

PMID- 19402196
TI  - Effect of exogenous nitric oxide on murine splenic immune response induced by
      Aggregatibacter actinomycetemcomitans lipopolysaccharide.
AB  - The aim of this study was to determine the effect of exogenous nitric oxide (NO)
      on the induction of murine splenic immune response to Aggregatibacter
      actinomycetemcomitans lipopolysaccharide (LPS) in vitro. BALB/c mice were
      immunized with A. actinomycetemcomitans LPS and a control group was sham
      immunized. Spleen cells were obtained, cultured and stimulated with A.
      actinomycetemcomitans LPS with or without the presence of S-nitroso acetyl
      penicillamine (SNAP), a NO donor, and carboxy-PTIO, an NO scavenger. Culture
      supernatants were assessed for inducible nitric oxide synthase (iNOS) activity,
      specific IgG subclass levels, and both IFN-gamma and IL-4 levels. The results
      showed that in A. actinomycetemcomitans LPS-stimulated cells, SNAP enhances iNOS
      activity but inhibits the levels of specific IgG2a and IFN-gamma suggesting a Th1
      response. The effect of SNAP on these immune parameters was ablated by carboxy
      PTIO. These results suggest that exogenous NO may suppress the Th1-like immune
      response of A. actinomycetemcomitans LPS-stimulated murine spleen cells.

PMID- 19402197
TI  - MLST analysis reveals a highly conserved core genome among poultry isolates of
      Clostridium septicum.
AB  - Clostridium septicum is a highly virulent, anaerobic bacterium capable of
      establishing necrotizing tissue infections and forming heat resistant endospores.
      Disease is primarily facilitated by secretion of numerous toxic products
      including a lethal pore-forming cytolysin. Spontaneously occurring clostridial
      myonecrosis involving C. septicum has recently reemerged as a concern for many
      poultry producers. However, despite its increasing prevalence, the epidemiology
      of infection and population structure of C. septicum remains largely unknown. In
      this study a multilocus sequence typing (MLST) approach was utilized to examine
      evolutionary relationships within a diverse collection of C. septicum isolates
      recovered from poultry flocks experiencing episodes of gangrenous dermatitis. The
      109 isolates examined represented 42 turkey flocks and 24 different flocks of
      broiler chickens as well as C. septicum type strain, ATCC 12464. Isolates were
      recovered predominantly from gangrenous lesions although isolates from livers,
      gastrointestinal tracts, spleens and blood were included. The loci analyzed were
      csa, the major lethal toxin produced by C. septicum, and the housekeeping genes
      gyrA, groEL, dnaK, recA, tpi, ddl, colA and glpK. These loci were included in
      part because of their previous use in MLST analysis of Clostridium perfringens
      and Clostridium difficile. Results indicated a high level of conservation present
      within these housekeeping gene fragments when compared to what has been
      previously reported for the aforementioned clostridia. Of the 5352 bp of sequence
      data examined for each isolate, 99.7% (5335/5352) was absolutely conserved among
      the 109 isolates. Only one of the ten unique sequence types, or allelic profiles,
      identified among the isolates was recovered from both turkeys and broiler
      chickens suggesting some host species preference. Phylogenetic analyses
      identified two unique clusters, or clonal complexes, among these poultry isolates
      which may have important epidemiological implications for poultry producers in
      the United States. This work indicates a predominantly clonal population
      structure for C. septicum although some evidence of recombination was also
      observed.

PMID- 19402198
TI  - Double ventricular response via dual atrioventricular nodal pathways resulting in
      sustained supraventricular nonreentrant tachycardia.

PMID- 19402199
TI  - A young child with palpitations.

PMID- 19402200
TI  - Immunoprophylaxis against important virus disease of horses, farm animals and
      birds.
AB  - Since the refinement of tissue culture techniques for virus isolation and
      propagation from the mid 1960s onwards, veterinary virology has received much
      academic and industrial interest, and has now become a major global industry
      largely centred on vaccine development against economically important virus
      diseases of food animals. Bio-tech approaches have been widely used for improved
      vaccines development. While many viral diseases are controlled through
      vaccination, many still lack safe and efficacious vaccines. Additional challenges
      faced by academia, industry and governments are likely to come from viruses
      jumping species and also from the emergence of virulent variants of established
      viruses due to natural mutations. Also viral ecology is changing as the
      respective vectors adapt to new habitats as has been shown in the recent
      incursion by bluetongue virus into Europe. In this paper the current vaccines for
      livestock, horses and birds are described in a species by species order. The new
      promising bio-tech approaches using reverse genetics, non-replicating viral
      vectors, alpha virus vectors and genetic vaccines in conjunction with better
      adjuvants and better ways of vaccine delivery are discussed as well

PMID- 19402201
TI  - Respiratory function as a marker of bone health and fracture risk in an older
      population.
AB  - Identification of those at high risk of osteoporosis and fractures using
      clinically available tests beyond BMD measures is a major clinical challenge. We
      examined forced expiratory volume in 1 s (FEV1), an easily obtainable measure of
      respiratory function, as a clinical measure for fracture prediction. In the
      context of the European Prospective Investigation into Cancer-Norfolk Study, 8304
      women and 6496 men 42-81 yr of age underwent a health check including spirometry
      and heel quantitative ultrasonography between 1997 and 2000 and were followed up
      for incident hip fractures until 2007. The main outcome measures were broadband
      ultrasound attenuation (BUA) of the heel (cross-sectional analysis) and hip
      fracture risk (prospective analysis). In multivariate regression models, a 1
      liter increase in FEV1 was associated with a statistically significant 2.2-dB/MHz
      increase in BUA, independent of age, smoking, height, body mass index, history of
      fracture, and use of corticosteroids. Mean FEV1 was significantly lower among 84
      women and 36 men with hip fracture compared with other participants. In
      multivariate proportional-hazard regression models, the relative risk (RR) of hip
      fracture associated with a 1-liter increase in FEV1 was 0.5 (95% CI, 0.3-0.9; p <
      0.001) for both men and women. RR of hip fracture for a 1 SD increase in FEV1 was
      approximately equivalent to a 0.5 SD increase in BUA among women (1 SD among men)
      and an 5-yr decrease in age among both men and women. Middle-aged and older
      people with low respiratory function are at increased risk of osteoporosis and
      hip fracture. FEV1, an easy, low-cost, and feasible clinical measure, may help
      improve the identification of high-risk groups.

PMID- 19402202
TI  - A single-dose combination therapy that both prevents and treats anthrax
      infection.
AB  - Exposure to anthrax leaves susceptible hosts at prolonged risk of infection since
      spores can persist in vivo for months before germinating to cause life
      threatening disease. Anthrax vaccine adsorbed (AVA, the licensed US vaccine)
      induces immunity too slowly to protect susceptible individuals post-exposure.
      Antibiotics prevent the proliferation of vegetative bacilli but do not block
      latent spores from germinating. Thus, anthrax-exposed individuals must remain on
      antibiotic therapy for months to eliminate the threat posed by delayed spore
      germination. Unfortunately, long-term antibiotic treatment is poorly tolerated
      and frequently discontinued. This work explores whether administering a single
      dose of a long-acting antibiotic (Dalbavancin) combined with a rapidly
      immunogenic vaccine/adjuvant combination can provide seamless protection from
      anthrax with minimal patient compliance. Results show that significant protection
      is achieved by delivering a single dose of this therapeutic combination any time
      before through 3 days after anthrax exposure.

PMID- 19402203
TI  - An analysis of the natural course of subclinical hyperthyroidism.
AB  - BACKGROUND: Our aim was to evaluate the incidence rate of overt hyperthyroidism
      in a cohort of patients with subclinical hyperthyroidism and to assess the
      potential risk factors for the development of overt thyroid hyperfunction.
      METHODS: We performed a retrospective analysis in 75 patients (68 women, mean age
      62.2 +/- 14.2 years) with subclinical hyperthyroidism and different grades of
      serum thyrotropin (TSH) suppression. Incidence rate of overt hyperthyroidism and
      survival time, ie, time without requiring therapy for overt hyperthyroidism, were
      studied. RESULTS: Thirty-four patients (45.3%) developed overt hyperthyroidism
      and 15 (20.0%) reverted to normal TSH values. The incidence rate of overt
      hyperthyroidism was 9.69 cases per 100 patient-year in the whole population and
      4.12, 7.41, and 29.63 cases per 100 patient-year in subjects with initial TSH
      values of 0.30 to 0.49, 0.10 to 0.29, and <0.10 mU/L, respectively. Kaplan-Meier
      analysis of survival time curves showed that the development of overt thyroid
      hyperfunction was significantly related to the presence of symptoms of
      hyperthyroidism (P < 0.05) and low (<0.10 mU/L) TSH concentrations (P < 0.001). A
      stepwise multivariate Cox regression analysis showed that both symptoms and low
      TSH values were significant factors for progression to overt thyrotoxicosis.
      CONCLUSIONS: TSH concentration is the most powerful predictor in the outcome of
      patients with subclinical hyperthyroidism. Our results suggest that patients with
      values under 0.10 mU/L have the highest probability to develop overt thyroid
      hyperfunction. In patients with TSH values higher than this value, the risk of
      progression is notably lower.

PMID- 19402205
TI  - Lack of evidence for bacterial infections in skin in patients with systemic
      sclerosis.
AB  - BACKGROUND: In some patients with systemic sclerosis (SSc), persistent bacterial
      infection involving dermal microvascular endothelial cells may result in
      endothelial injury, leading to the obliterative microvasculopathy typical of the
      disease. Alternatively, in some patients with SSc persistent bacterial infection
      involving activated dermal fibroblasts or other cells found in scleroderma skin
      might result in the fibrosing features of this disease. In this study, we
      investigated bacterial infection in skin in patients with SSc. METHODS:
      Chlamydiae of many species are known to undergo persistent infection. Highly
      sensitive and specific PCR assays targeting chromosomal DNA sequences from C.
      trachomatis and C. pneumoniae were used to screen skin biopsy samples from each
      of 18 patients and 26 control individuals. Additional screening was performed
      using a highly sensitive "pan-bacteria" PCR screening system. RESULTS: All
      patient and control samples proved to be PCR-negative for both chlamydial
      species. Similarly, all patient and control samples were PCR-negative when the
      broad range pan-bacteria assay system was used. CONCLUSION: Although some caveats
      apply, the data presented here do not support the contention that persistent
      bacterial infections play an important role in the pathogenesis of SSc.

PMID- 19402204
TI  - Vaccination strategies to enhance local immunity and protection against
      Mycobacteriun tuberculosis.
AB  - To determine the immunogenicity and protective efficacy of the Mycobacterium
      tuberculosis 10 kD culture filtrate protein (CFP10), and to evaluate strategies
      that enhance local immunity, we used C57Bl/6 DR4 mice that were transgenic for
      human HLA DRB1 0401, because CFP10 contains epitopes for DRB1 0401 but not for
      C57Bl/6 mice. Intramuscular immunization with a DNA vaccine encoding CFP10
      elicited production of IFN-gamma by systemic CD4+ T cells, and one intravenous
      dose of the CFP10-based DNA vaccine coated with polyethylenimine (PEI) stimulated
      IFN-gamma production by lung CD4+ cells and reduced the pulmonary bacillary
      burden. We conclude that CFP10 is a potential vaccine candidate and that coating
      vaccines with PEI enhances local protective immunity to tuberculosis

PMID- 19402207
TI  - Skeletal muscle abscess caused by Blastomyces dermatitidis.
AB  - Muscle involvement is an extremely rare manifestation of blastomycosis. We,
      therefore, report a case of a large gluteal muscle abscess caused by Blastomyces
      dermatitidis in a young, immunocompetent male. In addition, we review the
      literature to further characterize the syndrome of skeletal muscle blastomycosis.

PMID- 19402208
TI  - Castleman's disease presenting as fever of unknown origin: diagnostic value of
      fluorodeoxyglucose-positron emission tomography/computed tomography.

PMID- 19402206
TI  - Bifunctional chimeric fusion proteins engineered for DNA delivery: optimization
      of the protein to DNA ratio.
AB  - BACKGROUND: Cell penetrating peptides (CPPs) have been used to deliver nucleotide
      based therapeutics to cells, but this approach has produced mixed results. Ionic
      interactions and covalent bonds between the CPPs and the cargos may inhibit the
      effectiveness of the CPPs or interfere with the bioactivity of the cargos.
      METHODS: We have created a bifunctional chimeric protein that binds DNA using the
      p50 domain of the NF-kappaB transcription factor and is functionalized for
      delivery with the TAT CPP. The green fluorescent protein (GFP) has been
      incorporated for tracking delivery. The new chimeric protein, p50-GFP-TAT, was
      compared to p50-GFP, GFP-TAT and GFP as controls for the ability to transduce
      PC12 cells with and without oligonucleotide cargos. RESULTS: The p50-GFP-TAT
      construct can deliver 30 bp and 293 bp oligonucleotides to PC12 cells with an
      optimal ratio of 1.89 protein molecules per base pair of DNA length. This
      correlation was validated through the delivery of a fluorescent protein transgene
      encoded in a plasmid to PC12 cells. Thus, self-assembling CPP-based bifunctional
      fusion proteins can be engineered for the non-viral delivery of nucleotide-based
      cargos to mammalian cells. GENERAL SIGNIFICANCE: This work represents an
      important step forward in the rational design of protein-based systems for the
      delivery of macromolecular cargos.

PMID- 19402209
TI  - Brevibacillus brevis peritonitis.
AB  - We present what we believe is the first case of Brevibacillus (Bacillus) brevis
      peritonitis in a patient with hepatocellular carcinoma, possibly caused by the
      ingestion of fermented foods containing B. brevis spores. This case also
      demonstrates a pattern of antibiotic susceptibility with differing in vitro and
      in vivo bactericidal efficacy.

PMID- 19402210
TI  - Role of serum sodium in assessing hospital mortality in  cancer patients with
      spontaneous tumour lysis syndrome  inducing acute uric acid nephropathy.
AB  - Spontaneous tumour lysis syndrome (STLS) inducing acute uric acid nephropathy, a
      rare and neglected disease, presents more insidiously than conventional post
      treatment tumour lysis syndrome. Although STLS is a serious and potentially fatal
      complication in patients with neoplastic disorders, few investigations have
      addressed the relevance of clinical and laboratory features in assessing
      prognosis. A retrospective study was conducted, reviewing the records of all
      patients who developed acute renal failure (ARF) at Chang Gung memorial hospital
      between 1 July 1999 and 30 June 2003. STLS-induced acute uric acid nephropathy
      was identified in 12 of 1072 ARF patients (1.1%) during the study period. All
      patients had advanced stage tumours with large tumour burden, and 66.7% of cases
      had abdominal organ involvement. All 12 hyperuricemic patients became oliguric
      despite conservative therapy, and remained hyperuricemic (21.6 +/- 5.2 mg/dl)
      before dialysis therapy. Diuresis developed in eight patients (66.7%), with
      associated resolution of hyperuricemia, azotemia and metabolic derangements
      following dialysis initiation. Overall hospital mortality was 58.3%. Death in
      most patients was related to hyponatremia and hypoalbuminemia on admission. The
      serum sodium was found to have the best Youden index (0.86) and highest overall
      prediction accuracy (93%). Moreover, serum sodium and serum albumin for
      individual patients were significantly and positively correlated (r = 0.617, p =
      0.032). This investigation confirms a grave prognosis for cancer patients with
      STLS inducing acute uric acid nephropathy. Hyponatremia and hypoalbuminemia on
      the first day of admission indicate poor prognosis in such patients.

PMID- 19402212
TI  - Protein disulfide isomerase overexpression in vascular smooth muscle cells
      induces spontaneous preemptive NADPH oxidase activation and Nox1 mRNA expression:
      effects of nitrosothiol exposure.
AB  - Mechanisms regulating NADPH oxidase remain open and include the redox chaperone
      protein disulfide isomerase (PDI). Here, we further investigated PDI effects on
      vascular NADPH oxidase. VSMC transfected with wild-type PDI (wt-PDI) or PDI
      mutated in all four redox cysteines (mut-PDI) enhanced (2.5-fold) basal cellular
      ROS production and membrane NADPH oxidase activity, with 3-fold increase in Nox1,
      but not Nox4 mRNA. However, further ROS production, NADPH oxidase activity and
      Nox1 mRNA increase triggered by angiotensin-II (AngII) were totally lost with PDI
      overexpression, suggesting preemptive Nox1 activation in such cells. PDI
      overexpression increased Nox4 mRNA after AngII stimulus, although without
      parallel ROS increase. We also show that Nox inhibition by the nitric oxide donor
      GSNO is independent of PDI. PDI silencing decreased specifically Nox1 mRNA and
      protein, confirming that PDI may regulate Nox1 at transcriptional level in VSMC.
      Such data further strengthen the role of PDI as novel NADPH oxidase regulator.

PMID- 19402211
TI  - The role of nitrite ion in phagocyte function--perspectives and puzzles.
AB  - Macrophages and neutrophils are essential elements of host cellular defense
      systems that function, at least in part, by generating respiration-driven
      oxidative toxins in response to external stimuli. In both cells, encapsulation by
      phagocytosis provides a mechanism to direct the toxins against the microbes. The
      toxic chemicals formed by these two phagocytic cells differ markedly, as do the
      enzymatic catalysts that generate them. Nitrite ion is microbicidal under certain
      conditions, is generated by activated macrophages, and is present at elevated
      concentration levels at infection sites. In this review, we consider potential
      roles that nitrite might play in cellular disinfection by these phagocytes within
      the context of available experimental information. Although the suggested roles
      are plausible, based upon the chemical and biochemical reactivity of NO2(-),
      studies to date provide little support for their implementation within
      phagosomes.

PMID- 19402214
TI  - Stacks in canonical RNA pseudoknot structures.
AB  - In this paper we study the distribution of stacks/loops in k-non-crossing, tau
      canonical RNA pseudoknot structures (k,tau-structures). Here, an RNA structure is
      called k-non-crossing if it has no more than k-1 mutually crossing arcs and tau
      canonical if each arc is contained in a stack of length at least tau. Based on
      the ordinary generating function of k,tau-structures [G. Ma, C.M. Reidys,
      Canonical RNA pseudoknot structures, J. Comput. Biol. 15 (10) (2008) 1257] we
      derive the bivariate generating function T(k, tau)(x, u) =
      Sigma(n>or=0)Sigma(0<or=t<or=n/2 T(k,tau)(n, t)u(t)x(n), where T(k,tau)(n, t) is
      the number of k,tau-structures having exactly t stacks and study its
      singularities. We show that for a specific parametrization of the variable u,
      T(k, tau)(x, u) exhibits a unique, dominant singularity. The particular shift of
      this singularity parametrized by u implies a central limit theorem for the
      distribution of stack-numbers. Our results are of importance for understanding
      the 'language' of minimum-free energy RNA pseudoknot structures, generated by
      computer folding algorithms.

PMID- 19402213
TI  - Glucose-modulated tyrosine nitration in beta cells: targets and consequences.
AB  - Hyperglycemia, key factor of the pre-diabetic and diabetic pathology, is
      associated with cellular oxidative stress that promotes oxidative protein
      modifications. We report that protein nitration is responsive to changes in
      glucose concentrations in islets of Langerhans and insulinoma beta cells.
      Alterations in the extent of tyrosine nitration as well as the cellular
      nitroproteome profile correlated tightly with changing glucose concentrations.
      The target proteins we identified function in protein folding, energy metabolism,
      antioxidant capacity, and membrane permeability. Nitration of heat shock protein
      60 in vitro was found to decrease its ATP hydrolysis and interaction with
      proinsulin, suggesting a mechanism by which protein nitration could diminish
      insulin secretion. This was supported by our finding of a decrease in stimulated
      insulin secretion following glycolytic stress in cultured cells. Our results
      reveal that protein tyrosine nitration may be a previously unrecognized factor in
      beta-cell dysfunction and the pathogenesis of diabetes.

PMID- 19402216
TI  - Aberrant pyramidal tract in medial lemniscus of brainstem in the human brain.
AB  - The aberrant pyramidal tract (APT) refers to the collateral pathway of the
      pyramidal tract through the medial lemniscus in the brainstem. We showed the
      presence of an APT in the normal human brain using diffusion tensor tractography.
      Diffusion tensor tractography showed that the motor tracts of the 28 hemispheres
      in 14 healthy normal individuals originated from the primary sensori-motor cortex
      and descended through the known pathway of the pyramidal tract. However, in five
      (17.9%) of the 28 hemispheres, we observed that the APT descended through the
      medial lemniscus from the midbrain to the pons, and then entered into the
      pyramidal tract at the upper medulla, after which it descended through the
      pyramidal tract to the lower medulla.

PMID- 19402215
TI  - Fludarabine-based reduced intensity  conditioning regimens for allogeneic 
      hematopoietic stem cell transplantation  in patients with aplastic anemia and 
      fungal infections.
AB  - Eighteen patients (12 men and 6 women) with aplastic anemia and active fungal
      infections (10 proven/probable; 8 possible) underwent stem cell transplantation
      using fludarabine combined with cyclophosphamide or total body irradiation.
      Peripheral blood stem cells (PBSC) were the main graft source and a combination
      of cyclosporine with either methotrexate or methylprednisolone was used for graft
      versus host disease prophylaxis. Fourteen patients (77.8%) achieved neutrophil
      engraftment after a median time of 11 d, while four died of fungal sepsis.
      Resolution of fungal infection occurred in 60% of patients with proven/probable
      infections and in 100% with possible fungal infections. At a median follow up of
      30 months, 11 patients (61.1%) were alive and well. Fludarabine-based
      conditioning regimens with PBSC transplantation can be used successfully in
      patients with aplastic anemia and fungal infections.

PMID- 19402217
TI  - Normalization of endothelial dysfunction  following renal transplantation is 
      accompanied by a reduction of circulating  visfatin/NAMPT. A novel marker of 
      endothelial damage?
AB  - Endothelial dysfunction is strongly linked to cardiovascular disease and outcome
      of patients with chronic kidney disease. We hypothesized that decreased
      inflammatory activity and increased adiponectin following transplantation could
      be one mechanism for a better endothelial health. Fifty-eight living donor kidney
      transplant non-diabetic recipients, 31 (23 male, 29 +/- 5 yr) on cyclosporine A
      and 27 (10 male, 26 +/- 5 yr) on tacrolimus immunsupression, were studied
      longitudinally. Visfatin, adiponectin, high sensitive C-reactive protein (hsCRP)
      levels, brachial artery flow mediated dilatation (FMD) and nitroglycerine
      mediated dilatation were measured before transplantation and on the 30th and 90th
      day after transplantation. Pre-transplantation visfatin, adiponectin and FMD
      values of patients were significantly higher than those of the controls (p <
      0.001 for all). All values decreased significantly 30 and 90 d post
      transplantation. Plasma visfatin and adiponectin, correlated negatively with FMD
      levels 90 d both before and after kidney transplantation (p < 0.001 for both).
      Endothelial function improved during the first month after transplantation, and
      the degree of improvement correlated to reductions in circulating visfatin,
      adiponectin and hsCRP levels. Of interest, the intracellular enzyme visfatin was
      the strongest predictor of FMD both before and after kidney transplantation and
      may thus reflect endothelial cell damage directly.

PMID- 19402219
TI  - Impact of ezetimibe on cholesterol  subfractions in dyslipidemic cardiac 
      transplant recipients receiving statin therapy.
AB  - BACKGROUND: Ezetimibe decreases cholesterol in cardiac transplant recipients
      intolerant to statins therapy. The effects of ezetimibe in addition to statins
      therapy and its relationship with the magnitude of dyslipidemia and statins
      utilization have not been studied in cardiac transplant recipients. METHODS: The
      design of this investigation was a retrospective case control study. Twenty-two
      patients receiving the combination of therapy of statins plus ezetimibe were
      compared with 43 patients treated with statins only. The endpoints were assessed
      after three months of follow-up. RESULTS: The addition of ezetimibe decreased low
      density lipoprotein-cholesterol by 25% compared with a 4% increase in patients
      receiving statins only. The impact of ezetimibe was similar regardless of the
      magnitude of dyslipidemia or statins dosage. Ezetimibe increase high density
      lipoprotein (HDL)-cholesterol only in patients with baseline HDL-cholesterol
      above 1.3 mM/L (p < 0.05). There was an asymptomatic, but significant increase in
      creatinine kinase level [+31.4 +/- 8.1 (ezetimibe) vs. + 1.5 +/- 5.0 mM/L
      (placebo); p = 0.005]. CONCLUSION: Ezetimibe therapy provides a significant
      reduction in most cholesterol subfractions regardless of the magnitude of
      dyslipidemia and statins dosage.

PMID- 19402218
TI  - Selective phosphodiesterase-3 inhibitor cilostazol ameliorates experimental
      autoimmune encephalomyelitis.
AB  - We investigated the possible therapeutic effect of cilostazol, a specific
      inhibitor of phosphodiesterase-3, for experimental autoimmune encephalomyelitis
      (EAE). Mice affected with EAE induced by inoculation with MOG(35-55) were fed
      with cilostazol or vehicle control. The clinical EAE scores of the cilostazol-fed
      mice were lower than those of the controls. Serum level of soluble intercellular
      adhesion molecule-1 was significantly lower in the cilostazol-fed mice than in
      the controls. In the recall responses with MOG(35-55), proliferation and IFN
      gamma production by lymphocytes from cilostazol-fed mice were significantly
      reduced. Cilostazol may exhibit repressive effects on EAE by reducing the antigen
      specific T-cell response and decreasing the expression of the adhesion molecules.
      Cilostazol is a hopeful choice for the treatment of multiple sclerosis.

PMID- 19402221
TI  - Differences in prevalence, awareness, treatment and control  of hypertension
      between developing and developed countries.
AB  - Objective To systematically review quantitative differences in the prevalence,
      awareness, treatment and control of hypertension between developed and developing
      countries over the past 6 years. Methods We searched Medline [prevalence AND
      awareness AND treatment AND control AND (hypertension OR high blood pressure)]
      for population-based surveys. Prevalence, awareness, treatment and control of
      hypertension were compared between men and women, and between developing and
      developed countries, adjusting for age. The proportions of awareness, treatment
      and control were defined relative to the total number of hypertensive patients.
      Results We identified 248 articles, of which 204 did not fulfill inclusion
      criteria. The remaining articles reported data from 35 countries. Among men, the
      mean prevalence, awareness, treatment and control of hypertension were 32.2,
      40.6, 29.2 and 9.8%, respectively, in developing countries and 40.8, 49.2, 29.1
      and 10.8%, respectively, in developed countries. Among women, the mean
      prevalence, awareness, treatment and control of hypertension were 30.5, 52.7,
      40.5, and 16.2%, respectively, in developing countries and 33.0, 61.7, 40.6 and
      17.3%, respectively, in developed countries. After adjusting for age, the
      prevalence of hypertension among men was lower in developing than in developed
      countries (difference, S6.5%; 95% confidence interval, S11.3 to S1.8%).
      Conclusion There were no significant differences in mean prevalence, awareness,
      treatment and control of hypertension between developed and developing countries,
      except for a higher prevalence among men in developed countries. The prevalence,
      awareness, treatment and control of hypertension in developing countries are
      coming closer to those in developed countries.

PMID- 19402220
TI  - No apparent impact of increased  post-operative blood glucose levels on  clinical
      outcome in kidney transplant  recipients.
AB  - BACKGROUND: Our objective is to evaluate whether hyperglycemia in the first 48 h
      after renal transplantation is independently associated with rejection, post
      operative infection and post-transplant diabetes mellitus (PTDM) in a
      retrospective cohort study. METHODS: Patients who received a renal transplant in
      our hospital in 2003 or 2004 were included. Glucose values until 48 h after
      surgery were retrieved from laboratory reports. Biopsy proven acute rejection,
      culture proven infections and PTDM were scored until four months after
      transplantation. Data were analyzed using univariate analysis and logistic
      multivariate analysis. RESULTS: At least one post-operative glucose value could
      be retrieved for 150/151 patients. Rejection occurred in 46/150 (30.5%),
      infection in 47/150 (31.1%) and PTDM in 19/150 (12.6%) patients. When corrected
      for other risk factors, no relation was found between post-operative glucose
      levels and rejection (weak inverse relation, OR = 0.82; 95% CI = 0.65-1.03; p =
      0.09), post-operative glucose and infections (OR = 0.98; 95% CI = 0.80-1.21; p =
      0.84) and post-operative glucose and PTDM (OR = 0.93; 95% CI = 0.70-1.23; p =
      0.63). CONCLUSION: Increased post-operative blood glucose levels after renal
      transplantation were not found to be a risk factor for graft rejection. Also,
      post-operative glucose levels were not found to be associated with PTDM and post
      operative infections.

PMID- 19402222
TI  - Orthostatic hypotension in genetically related hypertensive  and normotensive
      individuals.
AB  - OBJECTIVES: Prevalence and determinants of orthostatic hypotension remain largely
      unexplored in younger individuals without significant burden of chronic diseases.
      METHODS: We investigated frequency and main associations of impaired orthostatic
      response in a cohort of 469 middle-aged hypertensive patients and 453 of their
      normotensive first-degree relatives. RESULTS: 13.4% of hypertensive and 5.5% of
      normotensive study participants were found to have orthostatic hypotension. In a
      backward logistic regression the following determinants of orthostatic
      hypotension were identified: sex [female, odds ratio (OR) 2.45, 95% confidence
      interval (CI) 1.14-5.25, P=0.022], reduced glomerular filtration rate [OR (per
      ml/min/1.73 m2) 0.97, 95% CI 0.94-0.99, P=0.002], systolic [OR (per mmHg) 1.02,
      95% CI 1.00-1.05, P=0.047] and diastolic blood pressure [OR (per mmHg) 1.04, 95%
      CI 1.00-1.09, P=0.033], and antihypertensive treatment (OR 0.41, 95% CI 0.18
      0.93, P=0.034). In hypertensive patients use of angiotensin-converting enzyme
      inhibitors was related to lower orthostatic hypotension frequency. Percentage of
      orthostatic hypotension-positive patients in the highest blood pressure stratum
      (> or = 160 mmHg) decreased from 20.2 to 7.6, when diagnostic criteria of
      orthostatic hypotension were adjusted for mean systolic orthostatic reaction (2
      SD value: 30 mmHg) . During follow-up (t=6.6 years) individuals with impaired
      orthostatic response showed a trend towards increased total mortality (OR 2.16,
      95% CI 0.97-4.80, P=0.06) in a crude model. CONCLUSION: Prevalence of orthostatic
      hypotension in hypertensive patients is higher than in their normotensive first
      degree relatives. Independently of age, sex, and elevated blood pressure,
      orthostatic hypotension may be additionally determined by impaired renal
      function. Antihypertensive treatment seems to protect from orthostatic
      hypotension, in particular, use of angiotensin-converting enzyme inhibitors in
      hypertensive patients. The diagnostic criteria of orthostatic hypotension may
      need adjustment for initial supine systolic blood pressure to increase clinical
      accuracy. The prognostic value of impaired orthostatic response regarding risk of
      cardiovascular disease and mortality remains uncertain and requires further
      studies.

PMID- 19402223
TI  - Functional single nucleotide polymorphism-1026C/A  of inducible nitric oxide
      synthase gene with increased  YY1-binding affinity is associated with
      hypertension in a  Chinese Han population.
AB  - BACKGROUND: In our previous linkage analysis of Chinese hypertensive families, a
      hypertension susceptibility region on chromosome 17 was located at D17S1878,
      which encompasses the inducible nitric oxide synthase (iNOS) gene. OBJECTIVE: The
      aim of this study was to investigate the association between variant in the human
      iNOS gene and susceptibility to hypertension in Chinese Han. METHODS AND RESULTS:
      We detected the -1026C/A polymorphism of the iNOS promoter in 463 hypertensive
      patients and 432 normotensive individuals for purposes of an association analysis
      and in 76 hypertensive families with 318 members for purposes of transmission
      disequillibrium test analysis via real-time PCR with a Taqman-minor groove binder
      probe. There were significant differences in the genotype and allele frequencies
      of the iNOS-1026C/A (P<0.05); the genotype CC was associated with hypertension
      after adjusting for environmental risk factors via a nonconditional logistic
      regression analysis [adjusted odds ratio, 2.90; 95% confidence interval, 2.14
      3.93]. A transmission disequillibrium test-sib transmission disequillibrium test
      analysis demonstrated that the allele C was preferentially transmitted within a
      pedigree (combined Z score 2.257, P<0.05). The iNOS-1026C/A was identified by a
      construct reporter assay as a functional variant, and the transcriptional
      activity of the promoter with allele C was 4.73-fold lower than that with allele
      A. Furthermore, electrophoresis mobility shift assay showed that the -1026C/A
      changed the Y in Yang 1 (YY1)-binding pattern in vitro, whereas chromatin
      immunoprecipitation showed that transcription factor YY1 was bound to the -1026C
      element in vivo. Lipopolysaccharide, an inflammatory stimulating factor, could
      induce YY1 to augment DNA-binding affinity; it could also be involved in the
      inhibited transcriptional activity of the iNOS promoter with allele C.
      CONCLUSION: We thus conclude that iNOS-1026C/A with a change in YY1-binding
      affinity is associated with hypertension under the affect of inflammatory
      stimulating factors.

PMID- 19402224
TI  - Differential muscarinic receptor gene expression levels  in the ventral medulla
      of spontaneously hypertensive and  Wistar-Kyoto rats: role in sympathetic
      baroreflex function.
AB  - OBJECTIVE: We demonstrated previously that central muscarinic cholinergic
      receptor (mAChR) activation increased splanchnic sympathetic nerve activity and
      sympathetic baroreflex function via activation of mAChR in the rostral
      ventrolateral medulla (RVLM), and we found that some RVLM bulbospinal neurons
      contain muscarinic M2R mRNA. Here, we examined the gene expression, cellular
      distribution and functional role of muscarinic receptors in the RVLM in
      spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats.
      METHOD AND RESULTS: Using the sensitive technique of quantitative real time
      reverse transcriptase-PCR, M2R mRNA level was elevated two-fold (P<0.05) and M4R
      mRNA was downregulated two-fold (P<0.001), with all other receptors expressed at
      similar levels, in the rostral ventral medulla of SHR compared with WKY.
      Bulbospinal, but not catecholaminergic neurons, in the RVLM expressed M2R mRNA
      (M2RR), and similar numbers were found in the RVLM of SHR and WKY. Could elevated
      M2R within individual neurons or enhanced presynaptic activity reflects enhanced
      cholinergic effects in the RVLM? Activation of central mAChR using oxotremorine
      evoked a larger increase in mean arterial pressure in SHR compared with WKY
      (P<0.01); however, oxotremorine-induced increases in splanchnic sympathetic nerve
      activity, and sympathetic baroreflex function were similar in SHR and WKY.
      CONCLUSION: These data indicate that enhanced pressor responses in SHR, following
      centrally mediated mAChR activation, are not associated with RVLM-mediated
      constriction of the splanchnic circulation or effects on the sympathetic
      baroreflex, but could reflect modified mAChR gene expression elsewhere. RVLM
      dependent splanchnic sympathetic nerve activity effects, evoked by mAChR
      activation, are not mediated by the differential M2/M4 receptor mRNA levels
      identified in SHR compared with WKY.

PMID- 19402225
TI  - Increased arterial stiffness in familial  combined hyperlipidemia.
AB  - OBJECTIVE: The current study was conducted to investigate whether greater
      arterial stiffening is already present in normolipidemic relatives of patients
      with familial combined hyperlipidemia (FCHL), as compared with healthy controls,
      and to establish the factors that are associated with arterial stiffness in
      comparison with markers of atherosclerosis. METHODS: Seventy-seven FCHL patients,
      121 normolipidemic relatives and 72 spouses (controls) underwent ultrasound
      examination of the common carotid artery to determine the presence of plaques and
      the degree of arterial stiffness, expressed as stiffness index alpha. RESULTS:
      Age-adjusted and sex-adjusted analyses revealed that the arterial stiffness index
      alpha and prevalence of plaques were higher in normolipidemic relatives when
      compared with spouses, but lower than in FCHL patients (P<0.05). Additional
      adjustments for visceral obesity, smoking, plasma glucose, insulin, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides,
      pulse frequency and use of lipid-lowering or antihypertensive medication did not
      affect the results for arterial stiffness, whereas the adjusted prevalence of
      atherosclerosis was markedly lowered in FCHL patients. Logistic regression
      analyses demonstrated that age, male sex, pulse frequency and low-density
      lipoprotein cholesterol were significant independent determinants of
      atherosclerotic plaques. In contrast, only age and FCHL family status, that is,
      belonging to an FCHL family or not, contributed to arterial stiffness.
      CONCLUSION: Arterial stiffening and atherosclerosis appear to be greater in
      patients who are prone to develop FCHL, that is, normolipidemic FCHL family
      members, as compared with controls. These findings may add to our understanding
      of the increased prevalence of cardiovascular complications in not only FCHL
      patients, but also their siblings and offspring.

PMID- 19402226
TI  - Characterization and evolution of vertebrate indoleamine 2, 3-dioxygenases IDOs
      from monotremes and marsupials.
AB  - Indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO) are
      tryptophan-degrading enzymes that catalyze the first step in tryptophan
      catabolism via the kynurenine pathway. TDO is widely distributed in both
      eukaryotes and bacteria. In contrast, IDO has been found only in mammals and
      yeast. In 2007, a third enzyme, indoleamine 2,3-dioxygenase-2 (IDO2), was
      discovered. IDO2 is found not only in mammals but also in lower vertebrates.
      Interestingly, the Km value of IDO2 for L-Trp was 500-1000 fold higher than that
      of IDO1. In this study, we isolated both IDO1 and IDO2 cDNA from a monotreme, the
      platypus (Ornithorhynchus anatinus), and a marsupial, the gray short-tailed
      opossum (Monodelphis domestica). We characterized the recombinant proteins and
      those of other known IDO1/IDO2 in intact cells and a cell-free system. It was
      found that methylene blue may not be suitable reductant for IDO2, hence resulting
      in an underestimation of recombinant IDO2 activity. In intact cells, the Km value
      of IDO2 for L-Trp was estimated to be much higher than that of IDO1 and this high
      Km value appears to have been conserved during the evolution of IDO2. The protein
      encoded by the ancestor gene of IDO1 and IDO2 is likely to have had properties
      more similar to present day IDO2 than to IDO1.

PMID- 19402227
TI  - Detection of silent cerebrovascular lesions in individuals with 'masked' and
      'white-coat' hypertension by home blood pressure measurement: the Ohasama study.
AB  - Objective To investigate the risk of silent cerebrovascular lesions in
      individuals with masked hypertension (MHT) and white-coat hypertension. Methods
      Self-measured home blood pressure (HBP) and casual blood pressure (CBP)
      measurements were recorded in 1060 individuals at least 55 years of age (mean
      age, 66.3 years) in a general population of Ohasama, Japan. The relationships
      between silent cerebrovascular lesions (white matter hyperintensity and lacunar
      infarct) detected on MRI and four blood pressure groups [sustained normal blood
      pressure (SNBP), HBP <135/85 mmHg, CBP <140/ 90 mmHg; white-coat hypertension,
      HBP <135/85 mmHg, CBP > or =140/90 mmHg; MHT, HBP > or =135/85 mmHg, CBP <140/90
      mmHg; sustained hypertension, HBP > or =135/85 mmHg, CBP > or =140/90 mmHg] were
      examined using multivariate analysis adjusted for possible confounding factors.
      Results The odds ratios of sustained hypertension (1.74, 95% confidence interval
      1.18-2.57) and MHT (2.31, 95% confidence interval 1.32-4.04) for the presence of
      silent cerebrovascular lesions were significantly higher than the odds ratio of
      SNBP, whereas there was no significant difference between white-coat hypertension
      and SNBP (1.03, 95% confidence interval 0.75-1.41). The odds ratios for the
      presence of either lacunar infarct or white matter hyperintensity in the four
      groups were similar to those for silent cerebrovascular lesions. Conclusion The
      present study is the first to demonstrate that the risk of silent cerebrovascular
      lesions is higher with MHT than with SNBP and similar to that of sustained
      hypertension.

PMID- 19402228
TI  - Productive principles applied in new settings.

PMID- 19402229
TI  - Rolling out the productive ward.

PMID- 19402230
TI  - Reflecting on the Bush selection process.

PMID- 19402231
TI  - Is antimicrobial underexposure due to glomerular hyperfiltration a possible cause
      of increased mortality rate from bacterial infections in critically ill patients?

PMID- 19402232
TI  - Ultrasound imaging in anaesthesia: which is the optimal anatomic point to block
      the radial nerve in the axilla?

PMID- 19402233
TI  - Myocardial infarction during left upper lobectomy in a patient with a LIMA graft.

PMID- 19402234
TI  - The soul and the knee.

PMID- 19402235
TI  - Chemiluminescent PEG-PCL micelles for imaging hydrogen peroxide.
AB  - Hydrogen peroxide is one of the fundamental molecules of biology, regulating key
      cell signaling pathways and the development of numerous inflammatory diseases.
      There is therefore great interest in developing contrast agents that can detect
      hydrogen peroxide in vitro and in vivo. In this report, we present a new contrast
      agent for imaging hydrogen peroxide, termed the chemiluminescent poly(ethylene
      glycol)-b-poly(e-caprolactone) (PEGPCL) micelles (CPMs), which can detect
      hydrogen peroxide at nanomolar concentrations and chemiluminesce in the near IR
      range (676 nm) in the presence of hydrogen peroxide. The CPMs are composed of a
      PEG-PCL scaffold and have fluorescent dyes and peroxalate esters in their
      hydrophobic PCL core. The CPMs image hydrogen peroxide by undergoing a three
      component chemiluminescent reaction involving a peroxalate ester, a fluorescent
      dye, and hydrogen peroxide. The CPMs also have a stealth PEG corona to enhance
      their circulation half life. The CPMs should find numerous applications for
      imaging hydrogen peroxide because of their nanomolar sensitivity, small size, and
      stealth pegylated surface.

PMID- 19402236
TI  - What to do about sinusitis.  A step-by-step approach starts with a simple nasal
      wash.

PMID- 19402237
TI  - Cold fingers, cold toes? Could be Raynaud's.

PMID- 19402238
TI  - Experts revise guidelines for irritable bowel syndrome.

PMID- 19402239
TI  - Exercise, especially treadmill, eases peripheral artery trouble.

PMID- 19402240
TI  - By the way, doctor.  Do I need to take antibiotics before dental cleanings and
      other procedures to prevent infection in my hip prosthesis?

PMID- 19402242
TI  - A new species of Paracapillaroides (Nematoda: Capillariidae) parasitizing
      Nemadactylus bergi (Perciformes: Latridae) from the Argentine Sea.
AB  - A new nematode species, Paracapillaroides acanthocotylus sp. n., is described
      from the marine fish Nemadactylus bergi (Norman) (Latridae, Perciformes) from
      waters off Mar del Plata, Argentina (38 degrees 08'S, 57 degrees 32'W)
      (prevalence 81.8%, mean intensity 12.4 +/- 10.3). The new species is readily
      distinguished from P. agonostomi Moravec, Salgado-Maldonado et Caspeta-Mandujano,
      1999, the only known species of the genus, by having in both sexes a longer
      oesophagus in relation to total body length. Males of the new species have a
      shorter and more complex spicule and a markedly different morphology of the
      spicular sheath; the rays supporting the caudal bursa are also shorter and
      rounded, instead of digitiform. Furthermore, females of the new species have
      elevated vulval lips and longer eggs. The complex structure of both the spicule
      and spicular sheath is unique among all capillariids parasitizing cold-blooded
      vertebrates. This is the first record of a species of Paracapillaroides in the
      southwestern Atlantic Ocean.

PMID- 19402241
TI  - Neotropical Monogenoidea. 53. Gyrodactylus corydori sp. n. and redescription of
      Gyrodactylus anisopharynx (Gyrodactylidea: Gyrodactylidae), parasites of
      Corydoras spp. (Siluriformes: Callichthyidae) from southern Brazil.
AB  - Morphometric analyses are used to evaluate the taxonomic status of two sympatric
      variants of Gyrodactylus anisopharynx Popazoglo et Boeger, 2000 (forma "large
      pharynx" and forma "small-pharynx"). The parasites were collected from the
      Piraquara River and the Miringuava River, State of Parana, Brazil, between
      February 2005 and May 2006. A total of 132 parasites were measured from two
      hosts, Corydoras ehrhardti Steindachner and Corydoras paleatus (Jenyns). Eleven
      morphological features of the haptoral sclerites and pharynx were measured and
      analysed by discriminant analysis and principal components analysis. The results
      indicate that the observed morphological variation cannot be associated to
      intraspecific variation or phenotypic plasticity (P < 0.0001). Consequently, the
      two variants previously allocated in G. anisopharynx represent two independent
      species. Since the holotype was defined as the variant "large-pharynx",
      Gyrodactylus corydori sp. n. is proposed to accommodate specimens previously
      reported as "small-pharynx" variant of G. anisopharynx. Morphometric analyses
      showed that the hook, the anchor, and the pharyngeal bulb are significantly
      distinct (P < 0.0001) between G. corydori sp. n. and G. anisopharynx (s.s.). The
      new species is characterized by having hooks with point moderately curved, robust
      convex heel, convex shelf, toe concave moderately pointed with depression; deep
      bar with two submedial, posterior projections; anchors with robust superficial
      root; superficial bar with two small anterolateral projections; and male
      copulatory organ armed with two rows of spinelets.

PMID- 19402244
TI  - Medical emergencies in the dental office: what do I need?

PMID- 19402243
TI  - Two new Uredinales in the Phakopsoraceae on Fabaceae from Brazil.
AB  - Two new species of rust fungi (Basidiomycota, Uredinales) on Fabaceae from Minas
      Gerais, Brazil, are proposed. Cerotelium galactiae (on Galactia martii) is the
      first record of Cerotelium on Fabaceae from South America. Phakopsora sennae (on
      Senna bicapsularis) is the second Neotropical species of Phakopsora on genus
      Senna.

PMID- 19402245
TI  - What is patient abandonment?

PMID- 19402246
TI  - 5 ways to manage risk.

PMID- 19402247
TI  - Top 10 most frequently asked legal questions.

PMID- 19402248
TI  - The benefits of identifying removable prosthetic devices.

PMID- 19402249
TI  - Dentistry grapples with third-party issues.

PMID- 19402250
TI  - Re: JSLS(2008)12:332-334 Laparoscopic management of small bowel intussuesception
      in a 16-year-old with Peutz-Jeghers Syndrome.

PMID- 19402251
TI  - Re: JSLS(2008)12:295-298 Natural orifice surgery: Transdouglas surgery-a new
      concept.

PMID- 19402252
TI  - Tuber-specific expression of a yeast invertase  and a bacterial glucokinase in
      potato leads to an activation  of sucrose phosphate synthase and the creation  of
      a sucrose futile cycle.
AB  - Fluxes were investigated in growing tubers from wild-type potato (Solanum
      tuberosum L. cv.Desiree) and from transformants expressing a yeast invertase in
      the cytosol under the control of the tuber-specific patatin promoter either alone
      (EC 3.2.1.26;U-IN2-30) or in combination with a Zymomonas mobilis glucokinase (EC
      2.7.1.2; GK3-38) by supplying radiolabelled [14C]sucrose, [14C]glucose or
      [14C]fructose to tuber discs for a 90-min pulse and subsequent chase incubations
      of 4 and 12 h, and by supplying [14C]fructose for 2 h and 4 h to intact tubers
      attached to the mother plant. Contrary to the expectation that this novel route
      for sucrose degradation would promote starch synthesis,the starch content
      decreased in the transgenic lines.Labelling kinetics did not reveal whether this
      was due to changes in the fluxes into or out of starch. However,they demonstrated
      that glycolysis is enhanced in the transgenic lines in comparison to the wild
      type. There was also a significant stimulation of sucrose synthesis,leading to a
      rapid cycle of sucrose degradation and resynthesis. The labelling pattern
      indicated that sucrose phosphate synthase (SPS; EC 2.4.1.14) was responsible for
      the enhanced recycling of label into sucrose. In agreement, there was a 4-fold
      and 6-fold increase in the activation status of SPS in U-IN2-30 and GK3
      38,respectively, and experiments with protein phosphatase inhibitors indicated
      that this activation involves enhanced dephosphorylation of SPS. It is proposed
      that this activation of SPS is promoted by the elevated glucose 6-phosphate
      levels in the transgenic tubers.These results indicate the pitfalls of metabolic
      engineering without a full appreciation of the metabolic system and regulatory
      circuits present in the tissue under investigation.

PMID- 19402253
TI  - Recent attempts for improved influenza vaccines.

PMID- 19402254
TI  - Current and emerging therapies: an overview of incretin-based therapy in the
      management of type 2 diabetes.

PMID- 19402255
TI  - Insulin analog initiation and titration.

PMID- 19402256
TI  - Integrating innovative tools into the management of type 2 diabetes to improve
      patient self-management.

PMID- 19402257
TI  - Essential medicines out of reach for most people.

PMID- 19402258
TI  - Global measles deaths drop by 74%.

PMID- 19402259
TI  - Preventable injuries kill 2000 children every day.

PMID- 19402260
TI  - Experts set tolerable level for melamine intake.

PMID- 19402261
TI  - Resveratrol and cancer prevention.

PMID- 19402262
TI  - [Clinical guidelines on identification,  management and complications  of chronic
      kidney disease].
AB  - The key messages of these guidelines on chronic kidney disease are: Chronic
      kidney disease (CKD) is a public health problem due to its wide distribution,
      high rate of complications and cost. CKD is a common condition, its prevalence
      being about 10%, and is treatable if it is detected on time. A patient with CKD
      has a higher risk of cardiovascular mortality than of progression of its
      underlying renal disease. A new definition of CKD, based on estimated Glomerular
      Filtration Rate (eGFR) and kidney damage, facilitates its detection and
      management. CKD is detected with three simple tests: 1) Blood pressure
      measurement, 2) Detection of proteinuria or albuminuria in an isolated urine
      sample, and 3) Estimation of renal function (eGFR), based on serum creatinine,
      age, gender and race. The CKD risk groups are individuals with diabetes,
      hypertension and a family history of renal disease. The most cost-effective
      measures are to detect and treat diabetic and hypertensive patients in the
      community. Therapy must emphasize the maximal reduction of cardiovascular risk.
      The complications of CKD such as anemia and renal osteodystrophy can be
      identified and treated on time. Most patients with chronic kidney disease are
      detected in the community, therefore their initial care must be organized at the
      level of primary care, along with programs for hypertension and diabetes.

PMID- 19402263
TI  - [End-to-end anastomosis for aortic coarctation].

PMID- 19402264
TI  - [Diagnostic imaging of and surgical procedure for case with coronary aneurysm].

PMID- 19402265
TI  - Gradual filling up of TB drug pipeline: how can we play our role better?

PMID- 19402266
TI  - Weight gain in patients with tuberculosis treated under directly observed
      treatment short-course (DOTS).
AB  - SET UP: One Tuberculosis Unit (TU) in Tiruvallur district, Tamil Nadu, India
      where Tuberculosis (TB) patients treated under Directly Observed Treatment Short
      Course (DOTS) programme. OBJECTIVE: To identify the effects of weight gain among
      TB patients at the end of treatment on different factors such as socio-economic
      and demographic characteristics, smoking and drinking habits, treatment under
      supervision, the type of DOTS centres and problems in taking drugs. METHODS: TB
      patients registered between May 1999 and December 2004 formed the study
      population. Multiple regression method was used for the analysis. RESULTS: Among
      1557 smear-positive TB patients registered under DOTS programme, the changes in
      weight ranged from a loss of 4 kgs to a gain of 20 kgs at the end of TB
      treatment; the average change in weight was 3.22 kgs. The gain in weight at the
      end of treatment was associated with age (<45 years), DOT at government centres,
      no problems in taking drugs as reported by patients and cure rate. CONCLUSION:
      The findings showed that there is an association between gain in weight with DOT
      at government centres and cure of patients.

PMID- 19402267
TI  - Prevalence of tuberculous infection among school children in Kerala.
AB  - BACKGROUND: There is paucity of information on epidemiological situation of
      Tuberculosis (TB) in the State of Kerala. The DOTS strategy under the Revised
      National Tuberculosis Control Programme (RNTCP) was introduced in the year 1998
      to cover the entire State by 2002. OBJECTIVE: To estimate the prevalence of
      tuberculous infection among children attending 1-4th standard in a sample of
      selected schools in Kerala. METHODS: A cluster-sample school-based tuberculin
      survey was carried out in 70 schools selected by a two-stage sampling procedure.
      A total of 4821 children (including those with and without BCG scar) in the age
      group of 5-9 years were tuberculin tested using 1 TU PPD RT23 with Tween 80 and
      the maximum transverse diameter of induration was measured about 72 hours later.
      About 81% of the children were found to have BCG scars. Analysis was also
      undertaken by mixture model. RESULTS: While 67% of children without BCG scar and
      62% with scar did not elicit any induration at the test site, the mode or anti
      mode of reactions due to infection with tubercle bacilli could not be identified
      from the distribution graphs. Analysis by mixture model also did not provide the
      best fit thus precluding estimation of prevalence of infection. About 5% of
      children had reactions > or =10 mm, 3% had reactions > or =12 mm and 2% had
      reactions > or =14 mm. CONCLUSION: Low proportion of reactors indicated a low
      level of transmission of infection in Kerala. Considering the problems in
      interpretation of tuberculin survey data, it may not be feasible to use ARTI as
      an epidemiological parameter to monitor future trends of TB situation in the
      state.

PMID- 19402268
TI  - Efficacy of repeat sputum examination in RNTCP.
AB  - BACKGROUND: The guidelines of repeat sputum smear examination in initial smear
      negative patients (ISN), who also fail the antibiotic trial of three samples have
      been incorporated in the RNTCP diagnostic algorithm in India in 2005. This study
      was conducted to assess the utility of repeat sputum smear examination in
      symptomatic initial smear negative patients to detect new smear positives in the
      state of Delhi. MATERIAL AND METHODS: The monthly records of the laboratory
      abstracts for the six quarters for all the 24 districts of Delhi were analysed
      w.e.f. first of January 2006 to 30th June 2007. RESULTS: A total of 243,244 TB
      suspects were examined for diagnosis during the six quarters w.e.f. January 2006.
      Of these, 37,666 were found positive on sputum smear microscopy giving a
      positivity rate of 15.4%. During the same period, a total of 2,195 (1% of ISN )
      TB suspects underwent repeat sputum examination, of which 272 were found positive
      giving a mean positivity of 12.3%. CONCLUSION: A significant number of apparently
      smear negative TB cases may in fact be smear positive due to various reasons and
      can be detected by a simple repeat sputum examination. Yield of sputum positive
      cases in sputum reexamination is almost the same as in initial sputum examination
      i.e. 10-15%. Therefore, the policy of repeat sputum examination in symptomatic
      initial sputum negative cases failing the antibiotic trial should be meticulously
      followed as advocated in the RNTCP diagnostic algorithm.

PMID- 19402269
TI  - Isolation, characterisation and kinetic studies on SEVA TB ES-31 antigen, a
      metallo-serine protease of interest in serodiagnosis.
AB  - BACKGROUND: SEVA TB Excretory secretory-31 (ES-31) antigen, a glycoprotein
      isolated from M. tb H37Ra culture filtrate, was found to be useful in the
      serodiagnosis of pulmonary tuberculosis (TB), extrapulmonary TB and in HIV-TB
      coinfection. Further, it has been shown to be a zinc containing serine protease.
      AIM: To isolate and purify SEVA TB ES-31 antigen from M. tb H37Ra culture
      filtrate and study of its enzyme properties and peptide sequence. METHODS: ES-31
      antigen was purified from culture filtrate of M. tuberculosis H37Ra strain by
      ammonium sulphate precipitation, SDS-PAGE fractionation and FPLC. Protease
      activity of ES-31 antigen was studied using azocasein as substrate. ES-31 antigen
      was further fractionated by two dimensional polyacrylamide gel electrophoresis
      (2D PAGE) followed by LCMS-T analysis. RESULTS: Mycobacterial metallo-serine
      protease was purified 3096 fold from M. tb H37Ra culture filtrate protein.
      Purified enzyme showed optimum activity at pH 7.0 at 37 degrees C. Of the four
      substrates explored, the enzyme has shown maximum activity with azocasein and had
      a Km value of 0.01 mM with specific activity of 6250 x 10(-6) U/mg protein.
      Further, analysis of ES-31 antigen by 2D PAGE showed two protein spots (A and B).
      CONCLUSION: Kinetic studies on SEVA TB ES-31 protein, an immunogen with metallo
      serine protease activity are reported for the first time. Purified enzyme had a
      Km value of 0.01 mM with azocasein as substrate. Further, study on structure and
      biological role of serine protease will be of interest.

PMID- 19402270
TI  - Progress towards millennium development goals for TB control in seven Asian
      countries.

PMID- 19402271
TI  - Status report on RNTCP.

PMID- 19402272
TI  - Extensively drug resistance (XDR) tb is not always fatal.
AB  - The chance of incidence of XDR TB is on the rise due to improper use of second
      line anti-tubercular drugs. XDR-TB is very difficult to treat successfully and is
      often referred to as "virtually untreatable form of TB". We herein report a case
      of XDR TB confirmed by bacteriological examination in a WHO recognised laboratory
      who after 12 months of regular treatment improved both clinically and
      radiologically with sputum smear conversion. To the best of our knowledge, there
      has been no previous report of any similar case in literature.

PMID- 19402273
TI  - Isoniazid induced gynaecomastia: a case report.
AB  - Gynaecomastia due to anti-tubercular chemotherapy is a rare side effect.
      Isoniazid causing breast tissue enlargement has been very rarely reported. We
      report a 60-year old, male patient of Pulmonary Tuberculosis who was started on
      antituberculous treatment (ATT) with rifampicin (R), isoniazid (H), ethambutol
      (E) and pyrazinamide (Z) together for initial two months and R, H & E thereon.
      After five months of initiation of treatment, while receiving RHE, he developed
      painful bilateral gynaecomastia. Isoniazid was stopped and patient was continued
      on R & E till completion of the treatment up to nine months. After stopping
      isoniazid, his breast swelling subsided to some extent and became non-tender.
      Follow up, at six months, after stopping the course of treatment, patient was
      asymptomatic except for slight bilateral non-tender breast enlargement.

PMID- 19402274
TI  - Health of doctors: a cause of concern.

PMID- 19402275
TI  - Fight against chronic diseases (high blood pressure, stroke, diabetes and cancer)
      in Pakistan; cost-effective interventions.

PMID- 19402276
TI  - Usefulness of standard treadmill stress testing in women.
AB  - OBJECTIVE: To determine the usefulness of stress test to detect coronary artery
      disease in women in local population. METHODS: Patients coming for stress test
      were evaluated clinically and 835 patients were enrolled, 69.6% were men and
      30.4% were women. Chest pain was the main reason for referral for treadmill
      stress testing. Bruce protocol was used for stress. 85% of the maximum predicted
      heart rate was considered significant. RESULTS: Higher numbers of male patients
      were able to achieve the desired metabolic equivalents (METs) as compared to
      females. Diabetes was equally prevalent in both men and women while higher number
      of male patients had higher systolic blood pressure. Males were relatively older
      while females were relatively overweight. CAD was detected in 9.3% of men and
      5.5% of women. The number of cancelled and non conclusive results was
      significantly higher in women. Gender, age and BMI were predictors of positive
      results. CONCLUSION: The guidelines recommend using stress test as initial
      modality in most of women and this study validates this belief.

PMID- 19402277
TI  - The comparison of pulmonary functions in open versus laparoscopic
      cholecystectomy.
AB  - OBJECTIVE: To examine respiratory functions of patients after open and
      laparoscopic cholecystectomy and to compare the advantages. METHODS: Fifty five
      cases with cholelithiasis subjected to elective cholescystectomy were studied.
      The patients were divided into two groups. Open Cholecystectomy (OC) was
      performed on 27 cases (Group I), and Laparoscopic Cholecystectomy (LC) in 28
      cases (Group II). Respiratory function tests were performed 24 hours before the
      operation and on the 1st and 6th day after surgery. Blood gas values and
      anaesthesia periods were recorded. Forced expiratuary volume in the 1st second
      (FEV1), forced vital capacity (FVC) and FEV1/FVC values were also noted. RESULTS:
      FEV1, FVC and FEV1/FVC values on first post-operative day in all cases were
      statistically lower than the preoperative values (p = 0.0001). Percentage changes
      of respiratory function test was calculated preoperatively and 1st postoperative
      day. The changes in both groups showed a significant decrease in FEV1, FVC and
      FEVI/FVC in Group I compared to Group II (p = 0.0001 in FEV1, p = 0.007 in FVC
      and p = 0.004 in FEV1/FVC). There was no significant difference in respiratory
      function tests evaluated on the 6th postoperative day and they had returned to
      normal values. There was no difference among preoperative and postoperative
      PaCO2, pH values in arteriel blood gas values in all cases (p = 0.355 p = 0,215).
      These parameters did not differ in both groups (p = 0.527, p = 0.591), There was
      a significant decrease in PaO2 and O2 saturation in all cases (p = 0.0001), but
      there was no significant difference when both groups were compared (p = 0.166, p
      = 0.678). CONCLUSION: The better results of pulmonary function tests in patients
      subjected to LC proves the advantage of the procedure over OC.

PMID- 19402278
TI  - Prevalence and severity of premenstrual symptoms among Iranian female university
      students.
AB  - OBJECTIVE: To investigate the frequency of premenstrual symptoms and prevalence
      of PMS among young Iranian women. METHOD: A cross-sectional study was carried out
      in 2005 among female students of Zahedan University (Iran), aged 18-27 years.
      Overall 300 participants were asked to complete an anonymous questionnaire
      assessing premenstrual symptoms. The items of the questionnaire were derived from
      DSM-IV diagnostic criteria for premenstrual dysphoric disorder and PMS symptoms
      reported in existing literature. RESULTS: Of the 300 participants, 98.2% reported
      at least one mild to severe premenstrual symptom and 16% met the criteria of DSM
      IV for PMS. Most common symptoms were feeling of tiredness or lethargy (84%),
      depressed mood (72.3%), sudden feeling of sadness or tearfulness (70.3%), anxiety
      (70%), backache (69%) and sleep problems (66%). There was no significant
      difference in severity of symptoms based on marital status and living conditions
      (living with parents or away from parents), but severity of symptoms were
      significantly higher for the younger women (18-20 years) compared to the older
      women (21-24 and 25-27 years). CONCLUSION: High frequency of premenstrual
      symptoms and significant prevalence of PMS was found in our study sample.
      Preventive and treatment strategies for PMS is highly recommended.

PMID- 19402279
TI  - Quinine is bactericidal.
AB  - OBJECTIVE: To determine the antibacterial properties of Quinine dihydrochloride
      and its MIC. MATERIAL AND METHODS: A Quasi-Experimental study was conducted at
      the Jinnah Postgraduate Medical Centre, Karachi from July 2006 to November 2006.
      Two hundred samples of pus, blood, sputum and ascitic fluid, from hospitalized
      adult patients from Medicine ward (W-7) having different Bacterial infections
      were studied. Proforma was filled to document the demographic details. Samples
      were collected from different sites, isolated, identified and checked for
      antimicrobial susceptibility of quinine dihydrochloride by standard methods.
      RESULTS: Staphylococcus aureus, Escherichia coli, Proteus vulgaris, Pseudomonas
      aeruginosa and Salmonella typhi were inhibited at MIC of 125 g/ml. Streptococcus
      pyogenes was inhibited at MIC of 31.25 g/ml of quinine dihydrochloride (Dilution
      ranges from 31.25 g/ml to 1000 g/ml). CONCLUSION: The concomitant antimalarial
      and antibacterial action of Quinine dihydrochloride may be beneficial in
      developing countries adding to cost effectiveness of treatment provided to
      patients belonging to low socioeconomic group.

PMID- 19402280
TI  - Evaluation of pre transplant T-cell activation status by soluble CD 30
      determination.
AB  - OBJECTIVE: To evaluate the utility of serum CD30 (sCD30) levels as predictor of
      early acute graft rejection in live related renal transplant programme. METHODS:
      This prospective study included 50 consecutive renal transplant recipients who
      received their first live related renal allograft at the Sindh Institute of
      Urology and Transplantation (SIUT) between October 2006 and March 2007. Blood
      samples were obtained one day before transplantation and on the third and
      fourteenth posttransplant days. Blood samples were also obtained from 50, age and
      sex matched healthy control individuals. Levels of serum sCD30 were measured by
      Enzyme Linked Immunosorbent Assay (ELISA). RESULT: Donor-recipient blood group
      matching was identical in all patients. Pre-transplant lymphocyte crossmatch for
      T and B cells was negative, and panel reactive antibodies (PRA) were 0% for all
      recipients. The mean age of recipients was 31.6 +/- 10.23 years (range 5 to 55
      years), while mean donor age was 32.74 +/- 8.48 years (range 21-50 years). Eleven
      (22%) recipients and donors were HLA identical while remaining (78%) were one
      haplotype match. Average serum sCD30 pre-transplant levels (37.8 +/- 4.97U/ml)
      were significantly higher than those of healthy individual's mean value of 8.48
      +/- 4.97 U/ml, (P = 0.001). Eight (16%) patients developed acute rejection
      episode during this follow up period. Rejections were described and classified
      according to BANFF 97 classification. CONCLUSION: In this small single center
      study the serum levels of sCD30 did not show any significant difference between
      rejection and non rejection group in our transplant population.

PMID- 19402281
TI  - Frequency and risk factors for intestinal parasitic infection in children under
      five years age at a tertiary care hospital in Karachi.
AB  - OBJECTIVE: To assess the frequency and risk factors for intestinal parasitic
      infection in children under five years age at a tertiary care hospital, Karachi.
      METHODS: A cross sectional survey of 269 children under five years was conducted
      at a tertiary care hospital on a pretested self-administered questionnaire. Stool
      smears were examined under light microscope with direct saline smear and lugol's
      iodine solution. Parasitic detection was confirmed by formalin ethyl acetate
      concentration method. RESULTS: Stool test positive for parasites was found in 185
      (68.8%) children. Majority of children 144 (53.5%) were among 4-5 years of age.
      Less than one third (20.4%) showed moderate malnutrition (p = 0.05) while 44.6%
      were found to have mild anaemia (p < 0.001). Giardia lamblia was the most common
      parasite (25.3%) identified. Only 40% of children were found to wash hands with
      soap after using the toilet (p < 0.001). Eating mud/pica was present in 36%
      children (p < 0.001). Less than half (48%) of the mothers said that they do not
      purify drinking water (p < 0.001). CONCLUSION: The frequency of intestinal
      parasitic infection was found to be high among children under five years. Major
      contributory factors were lack of hand washing and drinking unpurified water
      along with habit of eating mud/pica. This study identifies at-risk population of
      less than five years of age who could benefit from health education of parents.

PMID- 19402282
TI  - Clinical and laboratory findings in acute malaria caused by various plasmodium
      species.
AB  - OBJECTIVE: To find out clinical and laboratory findings in acute malaria caused
      by various plasmodium species. METHODS: This study was conducted in Department of
      Medicine and Pathology, Combined Military Hospital, Quetta, Balochistan, from
      August 2006 to December 2006. Five hundred and two subjects with positive
      malarial parasite slide were included in the study. Frequencies of alterations in
      clinical and laboratory parameters were determined in various plasmodium species
      and reported in percentage. RESULTS: Of 502 patients, 311 were Plasmodium (P.)
      falciparum, 100 were P. vivax and 91 were mixed infection. Triad of fever, chills
      and sweating was present in 91% of subjects with all three varieties of P.
      infection. Splenomegaly was detected in 59-73% individuals with malaria.
      Thrombocytopenia was the leading haematological alteration associated with
      various P. species, seen in almost 80% of infected patients. Anaemia and Jaundice
      were more common in P. falciparum and mixed infection as compared to P. vivax.
      Serum urea, creatinine and plasma glucose were within normal limits in all the
      patients with malaria. CONCLUSION: Malaria must be considered as a leading
      differential diagnosis in an acutely febrile patient with one or more of
      abnormalities like splenomegaly, fall in blood counts or rise in bilirubin and
      serum alanine aminotransferase levels.

PMID- 19402283
TI  - Magnitude of initial default in pulmonary tuberculosis.
AB  - OBJECTIVE: To assess the magnitude and reasons of initial default in pulmonary
      tuberculosis patients, diagnosed at Nazimabad Chest Clinic, Karachi. METHODS:
      This prospective study was conducted over five months from 1st December 2007 to
      30th April 2008. Suspected tuberculosis patients were prescribed sputum AFB (Acid
      Fast Bacilli) smears for three samples. This study included the smear positive
      patients who did not collect their report and were therefore defaulters for
      initiation of anti-tuberculosis treatment. These patients were contacted on
      phone, reasons of defaults were enquired and they were offered free treatment.
      RESULTS: In the study period, out of 869 tuberculosis suspects, 224 were
      diagnosed as smear positive pulmonary tuberculosis. Of these 224, one hundred and
      sixty-two got themselves registered for treatment. The remaining 62/224 (27.67%)
      were initial defaulters. On telephonic contact, 55 (88.70%) were traceable while
      07/62 (11.29%) were Untraceable-defaulters. Twenty-four patients (38.70%)
      reported to the clinic and were registered for treatment. The most common reason
      for default was 'dissatisfaction with services at the clinic'. CONCLUSION: A high
      initial default for initiating Anti-Tuberculosis Therapy is a serious issue that
      needs to be addressed.

PMID- 19402284
TI  - Central corneal thickness of Pakistani adults.
AB  - OBJECTIVE: To determine the average central corneal thickness (CCT) of healthy
      adults in the ophthalmology clinic of a tertiary care hospital of Pakistan.
      METHODS: This was a cross-sectional study conducted in the ophthalmology clinics
      of Aga Khan University Hospital, Karachi Pakistan. One hundred normal subjects
      (200 eyes) were studied. An ultrasound pachymeter was used to measure CCT.
      RESULTS: The mean (+/- SD) age of the study population was 44.29 +/- 15.18 years
      with a median of 47 years (range: 16-73). Twenty three percent of the subjects
      had diabetes mellitus, 29% hypertension and 6% had history of ischaemic heart
      disease. The mean (SD) CCT measurements were 531.08 +/- 33.37) and 531.29 +/-
      33.33 micrometers in the right and left eyes respectively and were not
      significantly different from each other. There was no statistically significant
      correlation between CCT and IOP (r = 0.158, p = 0.12). We did not find a
      significant association between CCT and other independent variables like age,
      sex, presence of co-morbidity i.e. Diabetes Mellitus (DM), Hypertension (HTN),
      Ischaemic Heart Disease (IHD), myopia, hypermetropia, systemic and eye medication
      use. CONCLUSIONS: The average CCT values obtained in the hospital-based study
      closely match those of the African Americans. A population-based study would be
      needed to provide unbiased CCT estimate in Pakistani population.

PMID- 19402285
TI  - Gender differences and delay in presentation of childhood squint.
AB  - OBJECTIVE: To assess gender differences and delay in presentation of childhood
      squint in a tertiary care hospital. METHODS: It was a series of children
      presenting with squint at the Aga Khan University Hospital, Karachi, Pakistan. We
      retrospectively studied the cases presenting between February 2000 and July 2007.
      RESULTS: A total of 107 children with squint were seen. Of these, 55 (52.4%) were
      girls. A statistically significant difference was observed between the mean age
      at presentation (+/- SD) of boys and girls (3 years and 5 months vs 4 years and 5
      months p: < 0.05). Girls had a greater mean (SD) and median (range) delay in
      squint presentation than had boys (2 year 4 months +/- 3 years vs 3 years +/- 2
      year 8 months) and 2 year 3 months (1 month to 12 years) vs 1 year 3 months (1
      month to 14 years), respectively. Overall amblyopia was present in 25.3% (23/91)
      children. Girls also had a higher burden of amblyopia compared with their male
      counterparts though the difference was not statistically significant (P = 0.09).
      CONCLUSION: There was a significant gender difference in age at presentation of
      childhood squint in our study. Further research is recommended to explore the
      reasons for this.

PMID- 19402286
TI  - The impact of variation in the pulse sequence parameters on image uniformity in
      magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the practical impact of alteration of key imaging
      parameters of Magnetic Resonance Imaging on image quality and effectiveness
      provided by widely available fast imaging pulse sequences. METHODS: A tissue
      equivalent material for Magnetic resonance Imaging (MRI) has been produced from a
      polysaccharide gel, agros, containing gadolinium chloride chelated to Ethylene
      Diamine Tetra- Acetic acid (EDTA) with a sort of T1 and T2 values. Experimental
      variations in key parameters included echo time (TE) and repetition time TR.
      Quantitative analysis consisted of image nonuniformity. RESULTS: In T2 weighted
      images; any change in TE played a critical role in the signal homogeneity in all
      pulse sequences. The percentage of nonuniformity was incredibly high in T2
      weighted image but the change of TR was insignificant in T2-weighted study.
      Involving T1 weighted images, percentage of nonuniformity was high in gradient
      recalled echo (GRE), also noticeable in fast fluid attenuated recovery (FLAIR)
      but quite acceptable in fast spin echo (FSE) and conventional spin echo (CSE).
      CONCLUSION: Selection of parameters relatively simple in CSE both in T1, T2
      weighted study that maintains image uniformity and quality as well. GRE is a very
      sensitive pulse sequence for any variation in parameters and loose signal
      uniformity rapidly.

PMID- 19402287
TI  - Knowledge of emergency contraception among women of childbearing age at a
      teaching hospital of Karachi.
AB  - OBJECTIVES: To assess knowledge and attitudes about Emergency Contraception among
      women of childbearing age in Karachi, Pakistan. METHODS: A questionnaire based
      survey was conducted on 400 married women, attending the family practice clinics
      at a teaching hospital in Karachi, Pakistan from July to December 2006.
      Questionnaire was administered to women at the family practice clinic-seeking
      level of knowledge of emergency contraception (EC) and attitudes towards its use,
      Ethical requirements of informed consent and confidentiality were ensured Data
      was entered into Epi data and analyzed in SPSS. RESULTS: Eighty-eight percent of
      women were not aware of EC. 83% were housewives. Only a small number (11.5%) ever
      used EC to prevent pregnancy, out of those, the correct timing of effectiveness
      of post-coital pill was known to only 40% of women while none of these women were
      aware of the existence of Intra Uterine Contraceptive Device (IUCD) insertion as
      an option for EC About 50% of women identified general practitioners or family
      medicine clinics as their main sources of knowledge about EC. Increased
      advertising was considered desirable by 72% while 37% considered over the counter
      availability of EC pill desirable and only 36% of women were uncomfortable to use
      EC because of religious reasons. CONCLUSION: EC has a potential to offer women an
      important option for fertility control. Lack of women's knowledge about EC use
      and availability may account in part for its limited use. There is a need to
      improve women's education about EC. The primary health care providers can play a
      major role in informing their patients about emergency contraception.

PMID- 19402288
TI  - Antimicrobial activity of tigecycline against nosocomial pathogens in Pakistan: a
      multicenter study.
AB  - OBJECTIVE: To measure the in-vitro activity of various antibiotics including
      tigecycline against Gram negative and positive nosocomial aerobic isolates.
      METHODS: A total of 430 clinical isolates of both Gram positive (143) and
      negative (287) aerobic bacteria were used from 3 centres during the year 2006 and
      2007. Minimum inhibitory concentration (MIC) was determined using broth micro
      dilution panels. Antibiotic resistance was interpreted using CLSI guidelines.
      RESULTS: Most of the isolates were resistant to more than one drug. Resistance to
      tigecycline was not found. Tigecycline (1 microg/ml) had low MIC against
      organisms tested. CONCLUSION: This data indicates that tigecycline, a new drug in
      its class, has broad-spectrum in-vitro activity against both Gram negative and
      positive nosocomial isolates. Therefore, it may be a suitable drug to be used for
      the treatment of highly resistant nosocomial infections.

PMID- 19402289
TI  - Emergency maternal and child health training courses and advocacy to achieve
      millennium development goals in a poorly resourced country; challenges and
      opportunities.
AB  - Our three years' experience of Essential Surgical Skills-Emergency Maternal and
      Child Health (ESS-EMCH) Programme in Pakistan suggests that despite a compromised
      healthcare delivery system, a tangible improvement in the management of
      emergencies in pregnancy, the neonate and children can be achieved by adopting a
      novel but robust mechanism of effective advocacy along with provision of
      innovative, evidence based and high quality training for healthcare staff.

PMID- 19402290
TI  - Sonographic foetal measurements in a cohort of population of Karachi, Pakistan.
AB  - The purpose of this cross-sectional study was to establish reference intervals
      for sonographic measurements of foetal parameters in women with normal singleton
      pregnancies in a cohort of population of Karachi, Pakistan. It was conducted at
      the Ultrasound Clinic, and Ziauddin Memorial Hospital, Nazimabad, Karachi, from
      January 2003 to July 2004. The measurements of foetal biparietal diameter (BPD),
      head circumference (HC), abdominal circumference (AC) and femur length (FL) were
      carried out on commercially available ultrasound machines using a convex probe of
      3.5 MHz frequency. Four hundred women were enrolled; 358 women completed the
      study. Mean +/- SD, reference intervals and 5th and 95th centiles for the foetal
      parameters were computed. Regression equations calculated were BPD = -0.36 + 0.27
      x GA, (R2 = 0.97); HC = -0.96 + 0.05 x GA, (R2 = 0.95); AC = -0.345 + 0.33 x GA,
      (R2 = 0.95) and for FL = -1.50 + 0.24 x GA, (R2 = 0.97). [GA = gestational age in
      weeks, R2 = coefficient of determination]. In this cross-sectional study,
      predominantly of Urdu-speaking "mohajirs" (67.9%) the reference intervals of
      commonly used foetal parameters for assessing gestational age i.e. BPD, HC, AC
      and FL, were established. A larger, multi-centered study to encompass the
      different ethnic groups of the population is required.

PMID- 19402291
TI  - Spectrum of tamoxifen associated endometrial pathology in breast cancer patients.
AB  - The objective of the study was to determine the incidence and type of endometrial
      abnormalities in long-term users of tamoxifen with breast cancer. All patients
      with a diagnosis of Oestrogen Receptor positive breast cancer on Tamoxifen
      therapy who had also undergone endometrial biopsy for abnormal bleeding or other
      symptoms were included. Among the 37 cases that had long-term follow up
      available, 21(57%) had evidence of endometrial pathology. There were seven cases
      of simple hyperplasia and thirteen of endometrial polyp. Only one case of
      endometrial carcinoma was seen. These findings support the association between
      prolonged tamoxifen therapy and endometrial pathology of possible neoplastic
      potential. Endometrial pathology is dependent on duration of exposure to
      Tamoxifen, therefore, close follow up of such patients is recommended.

PMID- 19402292
TI  - Intra-operative cardiac monitoring by trans-oesophageal Doppler is not risk free
      in surgical patients.
AB  - The advancement of medical technology and future improvements in public health
      will lead to surgeons operating on high risk patients. One of these advances is
      to use intra-operative trans-oesophageal Doppler (TOD) to optimise fluid
      management. TOD is known to be the most effective technique for intraoperative
      cardiac monitoring. We report a case of a potentially life threatening
      complication from intraoperative TOD monitoring.

PMID- 19402293
TI  - A case of finger clubbing associated with nasopharyngeal carcinoma in a young
      girl, and review of pathophysiology.
AB  - Hypertrophic osteoarthropathy is characterized by clubbing of the digital tips
      and periosteal reaction of long bones. Most of the cases are associated with
      malignancy or other conditions such as congenital heart disease, liver cirrhosis,
      pulmonary fibrosis, biliary atresia and gastrointestinal polyps. Hypertrophic
      osteoarthropathy associated with malignancy is rare in children. A few cases of
      hypertrophic osteoarthropathy in children with nasopharyngeal carcinoma have been
      reported. This is a case of hypertrophic osteoarthropathy associated with
      nasopharyngeal carcinoma with lung and bone metastasis in a 16 year old girl. In
      this case, lung metastases progressed after intensive chemotherapy and
      hypertrophic osteoarthropathy (Clubbing) persisted.

PMID- 19402294
TI  - Asymptomatic missing Intrauterine Contraceptive Device found incidentally at
      laparatomy.
AB  - The aim of this presentation is to report an asymptomatic missing intrauterine
      contraceptive (IUD) found in the omentum at surgery for cholecystectomy. Patient
      presented with clinical features of chronic calculus cholecystitis. Missing IUD
      was found at exploratory laparatomy for cholecystectomy. Excision of omentum was
      done and the patient did well. IUD providers should not only screen potential
      users and insert IUD correctly, but also ensure adequate follow-up.

PMID- 19402295
TI  - Medical referees: how fair is the verdict?

PMID- 19402298
TI  - Effective patient education.

PMID- 19402297
TI  - One more time.

PMID- 19402296
TI  - Obesity induced magnesium deficiency can be treated by vitamin D supplementation.
AB  - OBJECTIVE: To determine the effect of vitamin D injection on Serum Magnesium
      concentration in obese and non obese women. METHOD: This Interventional study was
      performed on 82 women (17-50 years) which were randomly selected from general
      population of Tabriz city. They were assigned into two experimental groups. Obese
      group with stage 1 and 2 obesity and non obese group with normal weight. Weight
      was measured to the nearest 0.1 kg using a calibrated Seca scale. Height was
      measured using a cotton ruler which was pasted on the wall. Body mass index was
      calculated based on weight and height results. Biochemical parameters were
      measured before and after injection of 600000 IU doses of vitamin D. Serum
      Magnesium was measured calorimetrically and Serum 25 hydroxy vitamin D was
      estimated by Chemiluminescence Immune Assay method (CLIA). RESULTS: Baseline
      concentrations of serum Magnesium and 25 hydroxy vitamin D in obese individuals
      was lower than non obese individuals, the former being significant. Twenty seven
      percent of obese women versus 15% of non obese women were Magnesium deficient.
      Vitamin D injection caused a significant increase in serum Magnesium
      concentration in obese subjects but not in non obese subjects. There was also a
      significant increase of serum 25 hydroxy vitamin D in both groups. Mean elevation
      in serum Magnesium level among women who had Magnesium deficiency was higher than
      women with Magnesium adequacy (P < 0.05). CONCLUSION: Low serum Magnesium
      concentration in obese individuals can be modified by vitamin D injection.

PMID- 19402299
TI  - The state of South Dakota's child: 2009. Part 2--Children and poverty.
AB  - There is an inverse relationship between age and poverty in the United States,
      with 21 percent of children under six years of age poor, living below the Federal
      Poverty Guideline (FPG). In South Dakota, 17 percent of children under age 18 are
      poor, compared to 18 percent nationally, with 10 percent versus 11 percent of
      white children living below the FPG and 56 percent versus 33 percent of American
      Indian children living in poverty. In South Dakota, more than one-third of
      children living in single-parent households are poor, and 5 percent of those in
      married households live below the FPG. Nearly one-third of all children below the
      FPG live with their working poor families that have at least one parent with part
      or full-time employment. The effects of poverty on learning and development are
      reviewed with an emphasis on current findings suggesting that poverty in early
      childhood has long-term influences on health, regardless of an individual's
      movement beyond life in a low-income household.

PMID- 19402301
TI  - Pharmacogenomics: has our history become modern medicine?

PMID- 19402300
TI  - Walking forward: a program designed to lower cancer mortality rates among
      American Indians in western South Dakota.
AB  - Walking Forward is a community-based participatory research program in western
      South Dakota funded by the National Cancer Institute (NCI). The primary goal of
      this initiative is to address the high and ominously increasing cancer mortality
      rates among American Indians by facilitating access to innovative clinical
      trials, behavioral and genetic research and tailored patient navigation. The
      critical outcomes include: an unprecedented accrual rate of 25 percent in
      clinical trials, including cancer treatment and cancer control trials; a
      significant reduction in the number of missed treatment days among navigated
      American Indian cancer patients undergoing radiation therapy; and most
      importantly, establishment of trusting partnerships with the American Indian
      communities as reflected in enrollment in a genetic study involving the ataxia
      telangiectasia mutated gene. The results indicate that the Walking Forward
      approach presents an effective strategy to overcome the barriers to cancer care
      in this underserved community.

PMID- 19402302
TI  - A doctor's story.

PMID- 19402303
TI  - Legislation: where does health care fit in?

PMID- 19402304
TI  - Disaster-preparedness training for South Dakota health professions students.

PMID- 19402305
TI  - Brace yourself.

PMID- 19402306
TI  - The power of occupational health nursing.

PMID- 19402307
TI  - Local nursing students ignite the flame on fire prevention.

PMID- 19402308
TI  - Environment and health basics.

PMID- 19402310
TI  - [Osseointegration of dental implants after radiotherapy for oral cancer].
AB  - The goal of rehabilitation following radical surgery and radiotherapy for oral
      cancer is the restoration of oral functions and aesthetics. Osseointegrated
      implants improve prosthesis stability. Previous radiotherapy was originally
      considered a contraindication for implant placement. The aim of this study was to
      evaluate the survival of dental implants following radiotherapy. Nine oral cancer
      patients who had undergone radical surgery and radiotherapy were selected. A
      total of 23 implants were inserted. Twenty-one implants (91.3%) have been
      functioning without discomfort or infection. This study shows that
      osseointegrated implants should be considered part of the treatment plan for the
      rehabilitation of oral cancer patients after radiotherapy.

PMID- 19402309
TI  - [Changing approaches to traumatic injuries to primary and permanent teeth based
      on the reports published in 'Fogorvosi Szemle' in the past 100 years].
AB  - Most of the external forces hitting the body (automobile injuries, sport
      injuries, job accidents, falls, hits and fights) reach the head, and especially
      the oral and maxillofacial region. Statistics show the head is injured in more
      than 70 per cent of car accidents. The incidence of head injuries, specifically
      tooth injuries, is high among both infancy and school children. Authors give a
      review about the changing approaches of treatment principles in the reports
      published in the Hungarian dental journal 'Fogorvosi Szemle' in the past 100
      years, and how today's modern treatment trends have evolved.

PMID- 19402313
TI  - [The case of the 'presidential tumor']].

PMID- 19402311
TI  - [Dietary, oral hygienic habits, dental surgeon attendance, and social background
      in police student's population].
AB  - The aim of the study was to survey the dietary, oral hygienic habits, dental
      surgeon attendance and their relations with each other and social background in
      the Police School of Miskolc, Hungary. In this study, based on a questionnaire,
      792 students [(mean age: 20.43 +/- 1.25 ys (mean +/- S.D.)] participated.
      Statistical analysis was performed using SPSS for Windows 10.0 statistical
      software. The daily consumption of sweets was 30.8%. There was no significant
      difference between educational level of father and frequency of consumption of
      sweets. The frequency of consumption of sweets significantly decreased with
      increasing the number of siblings (p < 0.05). The daily consumption of soft
      drinks was 28.8%. In the examined population 10% of the students used dental
      floss, most of them (60.0%) cleaned their teeth twice a day. Frequency of tooth
      cleaning was significantly increased parallel to increase the educational level
      of father (p<0.05). Dental surgeon attendance aimed check up was 28.4% beside the
      compulsory yearly visit. The "3-times-tooth-cleaning" students visited their
      dentists within last 12 months in significantly higher percent than those of
      without daily tooth-cleaning (p < 0.05). There is a need to improve those factors
      which can affect oral health in the examined population.

PMID- 19402314
TI  - [Histological differential diagnosis of hydatidiform moles and hydropic
      abortions].
AB  - OBJECTIVE: To describe the diagnostic methods enabling histological differential
      diagnosis of complete hydatidiform mole, immature complete hydatidiform mole,
      partial hydatidiform mole, proliferative mole and hydropic abortion. METHODS: Our
      study consists of 1321 partial hydatidiform moles, 805 complete hydatidiform
      moles, 524 proliferative moles, and over 2500 hydropic abortuses diagnosed and
      treated at the Trophoblastic Disease Center in the Czech Republic (TDC-CZ),
      Institute for the Care of Mother and Child, plus 2896 of these lesions examined
      at the TDC-CZ by referral. The material was examined by routine histopathological
      methods, which in selected cases were supplemented by immunohistological
      examination and correlated with cytogenetic and molecular genetic results and
      clinical features. RESULTS: The study describes the diagnostic procedures
      enabling differential diagnosis between mature complete hydatidiform mole,
      immature complete hydatidiform mole, partial hydatidiform mole, proliferative
      mole and hydropic abortion. Fourteen histological parameters have been defined
      which are most common, individually or in combination, in various types of
      hydatidiform moles and hydropic abortions. Warning is given to errors in
      histological diagnosis, correlated with cytogenetic and molecular genetic
      results. We propose a reliable method of eliminating the influence of these
      errors on the possible development of trophoblastic disease. CONCLUSION: The
      study describes a histological differential diagnosis of complete hydatidiform
      mole, immature complete hydatidiform mole, partial hydatidiform mole,
      proliferative mole and hydropic abortion.

PMID- 19402315
TI  - [Merkel cell carcinoma--immunohistochemical study in a group of 11 patients].
AB  - The aim of our work was to confirm an immunohistochemical profile of routine
      markers of epithelial and neuroendocrine differentiation in eleven cases of
      Merkel cell carcinoma, as well as to study the expression of two markers of early
      phases of neuronal differentiation, namely reelin and class III beta-tubulin,
      markers which have not yet been studied in Merkel cell carcinomas. In all the
      investigated tumours the characteristic "dot-like" pattern of cytokeratin 20
      immunoexpression, as well as negative immunostaining for cytokeratin 7 and
      thyroid transcription factor 1 (TTF-1) were disclosed; all the tumours showed
      neuroendocrine differentiation, expressing either neuron specific enolase (NSE)
      or chromogranin A(CgA), or both. An interesting finding was observed when the
      anti-cytokeratin monoclonal antibody MNF 116 was used. The characteristic "dot
      like" pattern was detected in high proportion of tumours, including two samples
      of local recurrence of one of the carcinomas, where neoplastic cells have lost
      the expression of cytokeratin 20. The majority (91%) of Merkel cell carcinomas
      included in our group showed positive immunodetection of class III beta-tubulin
      when TU-20 antibody was used, while TuJ-1 immunostaining was surprisingly
      negative in all the investigated tumours. Detection of reelin was negative in
      almost all the studied Merkel cell carcinomas except for cases, where neoplastic
      cells revealed weak focal immunostaining in a minor portion of neoplastic cells.

PMID- 19402316
TI  - [Diagnostic possibility of celiac disease in bioptic practice].
AB  - Celiac disease is frequently a reason for the poor health children, but it also
      occurs in adults. This disease remains underdiagnosed, and not only in the Slovak
      and the Czech Republic populations. This is atypical celiac disease with
      extraintestinal symptomatology. This persistence is often recognized only after
      relapse. With regard to seeking out risk groups with atypical forms of the
      disease, there is the possibility of looking for various alternatives and
      combinations. Early diagnosis is possible and is preferred in clinical practice
      in the initial stage of the disease. In this work attention is given to the
      diagnostics of celiac disease in bioptic practice. A group of 40 newly-diagnosed
      patients--20 children with typical and 20 adult patients with atypical celiac
      disease--was selected. All the patients were examined by an expert
      gastroenterologist. Children and adolescents had typical symptoms, which were
      clinically expressed as celiac disease. Nevertheless, adult populations were
      repeatedly investigated without definitive diagnosis. Blood samples were taken
      for antiendomysial antibody detection, and after a positive result a biopsy of
      the duodenum was performed. Samples sent for histopathological examination were
      returned with the diagnostic conclusion of celiac disease. From a subjective
      point of view, there are no distinctions between the results, and some
      distinctions exist only in the clinical manifestations of the disease. With a
      view to increasing the diagnosis of celiac disease, various possibilities are
      described in this work, possibilities which remain within the specialty of
      pathology. The basic objective of this study was early, complex diagnosis of
      celiac disease in its typical and also atypical form. Among the methods are
      screening antibodies, histochemistry, immunohistochemistry and also
      electronmicroscopy. In selected parts of the work we present various
      considerations on the diagnosis of celiac disease, including our own
      recommendations for bioptic practice.

PMID- 19402317
TI  - [What is your diagnosis? Answer: middle ear adenoma].

PMID- 19402318
TI  - [Post-radiation dedifferentiation of meningioma into chondroblastic
      osteosarcoma].
AB  - We report a case of post-radiation dedifferentiation of meningothelial meningioma
      into chondroblastic osteosarcoma. The tumor developed in a 61-year-old man, seven
      years after adjuvant stereotactical radiotherapy of recurring meningioma.
      Histologically, there was a continuous transition from atypical meningioma into
      chondroblastic osteosarcoma. The patient died three weeks after the surgery,
      without additional oncological treatment. To our knowledge, this case represents
      only the second reported case of post-radiation dedifferentiation of meningioma
      into osteosarcoma.

PMID- 19402319
TI  - [Tomorrow it will happen. Reaction to standards through health inspection].

PMID- 19402320
TI  - [Intensive care. Minimal health care standards].

PMID- 19402321
TI  - [Clinical signs of cystic fibrosis in adult patients].

PMID- 19402322
TI  - [Improvement of 5 year survival rate after liver resection for colorectal
      metastases between 1984-2006].

PMID- 19402323
TI  - [Malformation of the V. cava inferior, a risk factor for deep venous thrombosis].

PMID- 19402326
TI  - [Intraperitoneal chemotherapy in ovarian carcinoma. Life prolonging in selected
      patients].

PMID- 19402324
TI  - [Diagnostic images (410) A women with a green toe nail. Chloronychia (green nail
      syndrome) caused by P. auruginosa].

PMID- 19402327
TI  - [Isolated infusion effective in melanoma and sarcoma. Good alternative for
      regional isolated cytostatic perfusion].

PMID- 19402328
TI  - [Necrosis of a hairy scalp as a first sign of arteritis temporalis].

PMID- 19402332
TI  - [Stroke - it still holds: "time is brain."].

PMID- 19402333
TI  - [Muscle cramps--differential diagnosis and therapy].
AB  - Calf cramps are sudden, involuntary, painful contractions of part of or the
      entire calf muscle that are visible, persist for seconds to minutes and then
      spontaneously resolve. They can occur with no identifiable cause, and are then
      referred to as common calf cramps. They may also be symptoms associated with
      diseases of the peripheral and central nervous system and muscle diseases. They
      also occur in association with metabolic disorders. In such cases the cramps are
      more extensive, intense and persist for longer. Cramp-fasciculation-myalgia
      syndrome additionally involves paresthesias and other signs of hyperexcitability
      of peripheral nerves. The recommended treatment for patients with frequent calf
      cramps causing significant impairment of well-being is oral administration of
      quinidine and/or botulinum toxin treatment of the calf muscles. During pregnancy
      both products are contraindicated, while probatory administration of magnesium is
      indicated.

PMID- 19402334
TI  - [Successful decolonisation of MRSA-positive patients].
AB  - The increasing number of patients colonised or infected with methicillin
      resistant Staphylococcus aureus (MRSA) is one of the major clinical and
      epidemiological problems worldwide. Besides the consistent prevention of further
      spread of resistant strains, decolonisation of MRSA carriers is crucial to curb
      the problem. Today, a wide range of highly effective, well-tolerated and
      relatively cost-effective antiseptics and disinfectants as well as a permanently
      increasing knowledge about colonization routes and critical points in therapy is
      available. Nevertheless, the prospects for sustainable decolonisation of carriers
      has been often evaluated as disappointing, in the past. This shows that a
      successful, sustainable decolonisation can only succeed if the antiseptic
      treatment is embedded in a sound overall concept. This article is meant to assist
      in finding safe, effective and successful decolonisation regimes for inpatient
      and outpatient MRSA-carriers based on current literature and authors' experience.

PMID- 19402335
TI  - [Pharmaceutical care for a multimorbid patient mainly suffering from chronic
      obstructive pulmonary disease].
AB  - In multimorbid patients the medication for COPD is associated with a high risk
      for drug-drug interactions, medication errors and adverse drug events. This
      article describes how the drug therapy of a patient with COPD was optimized using
      SOAP notes.

PMID- 19402336
TI  - [Greasy, sticky flakes from an uninflamed scalp in children?].

PMID- 19402338
TI  - Research Ethics Consultation at the Johns Hopkins Bloomberg School of Public
      Health.

PMID- 19402337
TI  - Reformed consent: adapting to new media and research participant preferences.

PMID- 19402339
TI  - Consent and population genomics: the creation of generic tools.

PMID- 19402340
TI  - Effects of nitric oxide donor antioxidants containing the phenol vitamin E
      substructure and a furoxan moiety on ischemia/reperfusion injury.
AB  - Nitric oxide (NO) donor antioxidants are a class of polyvalent drugs which is the
      focus of great interest today. They are potentially useful for the treatment of
      many forms of cardiovascular diseases, including the myocardial
      ischemia/reperfusion (I/R) damage which seems to be due to both a burst of
      reactive oxygen species (ROS) and a reduced release of NO during reperfusion. In
      this paper the results of a study on the ability of new NO-donor antioxidants
      containing the phenol vitamin E substructure and furoxan moiety to attenuate I/R
      damage are reported. The compounds under study are obtained by combining the
      phenol moiety (6-hydroxy-2,2,5,7,8-pentamethylchroman) present in vitamin E with
      differently substituted furoxan substructures endowed with different capacity of
      NO-release. Their antioxidant and NO-dependent vasodilator activities are
      reported. The I/R experiments were performed on isolated rat heart preparations
      perfused at a constant flow. After 20 min of stabilization, global ischemia was
      obtained by interrupting the perfusion for 30 min. After ischemia the hearts were
      reperfused for 2 h. The compounds were added to the perfusion buffer during the
      first 20 min of reperfusion. At the end of each experiment, the infarct size was
      measured with nitro-blue tetrazolium. From the results it appears that the
      limitation of the infarct area is favoured by an appropriate balance between NO
      donor and antioxidant properties and that these two actions are synergic.

PMID- 19402341
TI  - Comparative bioavailability of propafenone after administration of a magistral
      suspension vs. commercial tablets in healthy volunteers.
AB  - Propafenone (CAS 34183-22-7) is an effective antiarrhythmic drug used in
      children, although in some countries no specific pediatric formulation is
      available. The aim of this study is to compare the relative bioavailability of a
      magistral (MAG) preparation of propafenone versus its commercial (COM)
      presentation in a group of 16 Mexican healthy volunteers. Bioavailability was
      determined after crossover administration of the drugs, through a randomized two
      phase trial. All volunteers had normal hepatic and renal functions, determined
      clinically at the beginning of the study, and received 150 mg of either COM
      (tablets) or MAG (suspension). Blood samples were drawn for a 24-h post-dose
      analysis by HPLC to measure plasma levels of propafenone. Subjects (mean 25.9 +/-
      5.3 years and 66.1 +/- 12.4 kg) had the following pharmacokinetic parameters:
      Cmax 189.9 +/- 20.92 ng/mL, Tmax 1.5 h, AUC 322.4 +/- 36.28 ng x ml(-1) x h for
      COM. Values for MAG were Cmax 225.8 +/- 24.38 ng/mL, Tmax 1.7 h and AUC 359.3 +/-
      27.90 ng x ml(-1) x h. These values yielded a relative bioavailability of 111.42%
      for MAG compared with COM. No electrocardiographic changes were recorded in any
      subject with respect to the baseline value, in both treatment schemes. Therefore,
      propafenone suspension prepared as a magistral formulation may be used as an
      alternative drug in pediatric patients.

PMID- 19402342
TI  - Quantitative determination of ticlopidine hydrochloride in human plasma by high
      performance liquid chromatography-electronspray ionization mass spectrometry.
AB  - A sensitive, selective and simple high performance liquid
      chromatographyelectrospray ionization-mass spectrometry (HPLC-ESI-MS) was
      developed and validated for the quantification of ticlopidine hydrochloride (CAS
      53885-35-1) in human plasma using loratadine (CAS 79794-75-5) as internal
      standard (IS). Following liquid-liquid extraction, the analyte and the IS were
      extracted from plasma samples by n-hexane:isopropanol (95:5, v/v), separated by
      HPLC on a commercially available column (150 mm x 2.0 mm ID, 5 microm) with a
      mobile phase of acetonitrile: 10 mmol/L ammonium acetate buffer solution (85:15,
      v/v) and analyzed on a quadrupole mass spectrometer with ESI interface operating
      in the positive-ion mode. The correlation coefficient of the calibration curve
      was linear (r2 > 0.99) over the concentration range of 1-1000 ng/mL for
      ticlopidine hydrochloride. The intra- and inter-batch precisions were less than
      15% of the relative standard deviation and the accuracy ranged from 85 to 115% in
      terms of percent accuracy. The limit of detection (LOD) of ticlopidine
      hydrochloride was 0.5 ng/mL. The extraction recovery of ticlopidine hydrochloride
      was more than 80%. The proposed method enables the unambiguous identification and
      quantification of ticlopidine hydrochloride for pharmacokinetic, bioavailability
      or bioequivalence studies.

PMID- 19402343
TI  - Antioxidative and lipid lowering effects of 7,8-dihydroxy-3- (4-methylphenyl)
      coumarin in hyperlipidemic rats.
AB  - In this study, 7,8-dihydroxy-3-(4-methylphenyl) coumarin (DHMPC), a new coumarin
      derivative, was tested for the first time to determine whether it had any
      antioxidant and lipid lowering effects. Hypercholesterolemia was induced by
      feeding rats with a high cholesterol diet for 17 days. The lipid lowering and
      antioxidant effects of DHMPC were compared with those of hesperidin (CAS 520-26
      3) and rutin (CAS 153-18-4), which have been pharmacologically determined as
      potential lipid lowering and antioxidant agents. DHMPC significantly decreased
      total cholesterol levels but not as efficient as hesperidin. When the ratios of
      high density lipoprotein-cholesterol (HDL-cholesterol) to total cholesterol were
      evaluated, the most significant changes were observed in DHMPC and rutin
      treatments. The results of serum triglyceride levels indicate that DHMPC and
      hesperidin did not significantly decrease triglyceride level when compared to
      rutin group but prevented it to rise. Serum malondialdehyde (MDA) levels
      increased as expected in high cholesterol diet groups but no significant decrease
      was observed for serum MDA levels in all treated groups. In contrast to serum MDA
      levels, liver homogenates MDA levels decreased in all treated groups but a
      considerable decrease was not observed for DHMPC treated group. Liver homogenates
      glutathione (GSH) levels drastically decreased in hyperlipidemic group and
      increased in all treated groups. As a conclusion DHMPC displayed both antioxidant
      and lipid lowering effects and can be a candidate drug for further studies.

PMID- 19402345
TI  - Liquid chromatographic-mass spectrometry analysis and pharmacokinetic studies of
      erianin for intravenous injection in dogs.
AB  - The purpose of the present study was to examine the pharmacokinetic
      characteristics of erianin (2-methoxy-5-[2-(3,4,5-trimethoxyphenyl)-ethyl]
      phenol, CAS 95041-90-0), a nature product extracted from Dendrobium chrysotoxum,
      having notable antitumour activity, after intravenous injection of erianin fat
      emulsion to beagle dogs. An HPLC-MS method was developed to analyze the erianin
      levels in dog plasma and validated in a pharmacokinetic study. Plasma profiles
      were obtained after intravenous injection of erianin fat emulsion at the doses
      7.5, 15 and 30 mg/kg. The elimination half-life (t(1/2)) values for erianin were
      estimated to be 1.41+/- 0.31, 1.66 +/- 0.19, 1.60 0.28 h, while the mean area
      under concentration-time curve (AUC(0-infinity)) values were 1021.3 +/- 373.7,
      2305.1 +/- 597.0 and 3952.1 +/- 378.2 ng x h/ml, respectively. In conclusion, the
      present observations indicated that erianin plasma concentrations were clearly
      dose-proportional for the dose range studied. There was no gender difference in
      pharmacokinetics for erianin in male and female dogs.

PMID- 19402344
TI  - Fast HPLC method for the determination of ketoprofen in human plasma using a
      monolithic column and its application to a comparative bioavailability study in
      man.
AB  - A fast, specific, accurate, precise and reproducible high-performance liquid
      chromatography (HPLC) method with diode-array detector (DAD) was developed and
      validated for the determination of ketoprofen (CAS 22071-15-4) in human plasma
      using flubiprofen (CAS 5104-49-4) as an internal standard. The chromatographic
      separation was achieved on an onyx monolithic C18 (100 x 4.6 mm) analytical
      column with an isocratic mobile phase consisting of acetonitrile/potassium
      dihydrogen phosphate (KH2PO4) 0.01 M, (40:60, v/v) adjusted to pH 3.5. The flow
      was set at 5 ml x min(-1) and the wavelength at 254 nm. The total analysis time
      was less than 5 min. The ratio of peak area of analyte to internal standard was
      used for quantification. The limit of detection was defined as the ketoprofen
      concentration that produced a signal-to noise ratio greater than 3. The lower
      limit of quantification (LLOQ) was 10 ng x m(-1). At this level, the relative
      standard deviation (RSD) was lower than 13%. The calibration curve was linear
      over the concentration range 1-500 ng x ml(-1) with a minimum detectable limit of
      10 ng x ml(-1). The coefficients of variation for the inter-day and intra-day
      assay were found to be less than 11%. The present method was successfully applied
      to the routine analysis of human plasma samples collected from healthy volunteers
      after dermal application of two topical formulations containing ketoprofen in
      order to assess the relative bioavailability and to demonstrate that the systemic
      bioavailability of ketoprofen administered topically is low enough to ensure a
      low incidence of gastrointestinal adverse events.

PMID- 19402346
TI  - Comparison of primary human fibroblasts and keratinocytes with immortalized cell
      lines regarding their sensitivity to sodium dodecyl sulfate in a neutral red
      uptake cytotoxicity assay.
AB  - Cell lines present a valuable tool for in vitro assessment of skin damage caused
      by application of cosmeticals or pharmaceuticals. They form a reproducible test
      system under controllable test conditions and, in many cases, can be used as
      alternatives to animal testing in order to assess the compatibility of drugs or
      cosmetics and human skin. Yet, it can not necessarily be assumed that the
      behavior of cultured cells, when treated with different substances, is exactly
      consistent with the behavior of cells being part of a live organism. Becoming
      immortal, cells exhibit changes in genotype and/or phenotype, possibly resulting
      in modified reactions to external influences. Therefore, to obtain results close
      to in vivo studies, it seems apparent to use primary cells for testing that have
      not yet undergone any modifications. To compare the properties of primary
      fibroblasts (Normal Human Dermal Fibroblasts, NHDF) and primary keratinocytes
      (Normal Human Epidermal Keratinocytes, NHEK) with those of immortal cell lines
      (3T3 (ACC 173) Swiss albino mouse fibroblasts and HaCaT (human, adult, low
      calcium, high temperature, human adult skin keratinocytes) cells), their
      sensitivities in cytotoxicity assays have been assessed. While both fibroblast
      cell cultures showed similar sensitivities towards sodium dodecyl sulfate (SDS),
      primary keratinocytes died at SDS concentrations about three times lower than the
      immortal HaCaT cells.

PMID- 19402347
TI  - [Training requirements, expertise and basic conditions of committed medical
      educators in Germany].
AB  - BACKGROUND: Despite an increasing interest in undergraduate, postgraduate and
      continuing medical education, little is known about the training requirements,
      expertise and basic conditions of medical educators. Against this backdrop, we
      initiated a web-based survey amongst members of the "Gesellschaft fur
      Medizinische Ausbildung" (German Section of the Association for Medical Education
      in Europe) e.V. (GMA). METHODS: We conducted a web-based survey designed to
      answer the following questions: How do medical educators judge (1) their training
      requirements, (2) their expertise and (3) basic conditions. 147 out of 373
      members of the GMA e-mailing list responded to the questionnaire (overall
      response rate: 39%). RESULTS: The following were rated as high-priority training
      needs: development in medical education research methodology (56% of survey
      participants), student assessment (37%), supporting self-directed learning (35%),
      and computer-based training (32%). The highest level of expertise [Likert Scale:
      1 = very low to 5 = very high] was perceived in: general teaching principles
      (3.76 +/- 0.74), curriculum development (3.74 +/- 0.95), student assessment (3.65
      +/- 0.97] and evaluation of courses and curricula [3.65 +/- 0.9]. Regarding basic
      conditions, respondents noted a particular need for more funding in medical
      education [4.26 +/- 0.88] and more recognition of merits in medical education
      [4.20 +/- 0.92]. CONCLUSIONS: The survey respondents identified more training in
      research methodology and more academic recognition and funding as important
      challenges in the field of medical education.

PMID- 19402348
TI  - [Concept, implementation and evaluation of an interfaculty Master of Medical
      Education Programme].
AB  - The implementation of new medical licensing regulations (AAppO 2003) was the
      starting point for radical curricular changes in all German medical schools. In
      2004, the postgraduate and interfaculty Master of Medical Education (MME) degree
      programme was established at the University of Heidelberg under the auspices of
      the Medical Faculty Association (Medizinischer Fakultatentag, MFT) and supported
      by the Association for the Promotion of Science and Humanities in Germany
      (Stifterverband fur die Deutsche Wissenschaft). This new degree programme is
      intended to train multipliers and leaders in medical education, to build a German
      speaking network and to strengthen educational research. The eight one-week MME
      modules are organised by seven locations in Germany (Munich, Tuebingen,
      Muenster/Essen, Berlin, Heidelberg, Cologne, Dresden) and an annually changing
      international faculty. The instructor teams are composed of national and
      international experts. Major focal points include: curriculum development,
      education theory, teaching and exam methods, evaluations, team building and group
      dynamics, project management, leadership, and faculty development, as well as
      educational research. The modules are connected with each other longitudinally:
      each participant conducts a project to improve teaching in his or her own faculty
      and writes a master's thesis about an educational research project. Overall, the
      participants earn 60 ECTS (European Credit Transfer System) in the course of two
      years while working. So far 100 participants (25 per year) from 33 of 34 medical
      faculties have started the program and 19 participants (50% of the participants
      from Cohort 1, 29% of the participants from Cohort 2) completed the program. The
      evaluation of the individual modules showed a very high level of participant
      satisfaction. In two modules, the evaluation results demonstrated a need for
      change. In 2006, an external evaluation conducted by international experts
      positively highlighted the MME Programme structure as a leading example
      emphasizing all aspects of modern medical education, including relevant
      managerial skills. The MME Programme as a contribution to the professionalization
      of medical education in the German-speaking area has become firmly established.
      The impact of the MME Programme on the career development of its participants and
      the institutional development of the medical faculties still remains to be
      evaluated.

PMID- 19402349
TI  - [The sandwich principle--introduction to learner-centred teaching/learning
      methods in medicine].
AB  - Learning is a highly individual process that depends on multiple factors, e.g.,
      previous knowledge, level of attention, personal interest and motivation.
      Efficient learning may therefore be facilitated by offering individual learning
      phases during educational sessions. The sandwich design of teaching sessions
      represents a superior principle which supports efficient learning processes by
      integrating individual and collective learning phases and using a wide range of
      didactic methods.

PMID- 19402350
TI  - [The good PBL tutor--to be or not to be: instructional films for tutors].
AB  - INTRODUCTION: Many faculties worldwide apply the method of problem-based learning
      (PBL) in their curricula as a form of instruction by which students in small
      groups develop problem-solving strategies on the basis of a specific case. This
      approach fosters self-responsible and context-dependent learning, which aims at
      providing an improved anchoring of knowledge. For this reason, the previous
      decades have seen a distribution of the method to medical schools across the
      world. The role of the tutor assumes particular importance since, in contrast to
      the traditional university system, he or she serves as a facilitator who fosters
      and structures content-related and group-dynamic learning processes. In some
      cases, this requires an intervention by the tutor. The major challenge is to
      intervene at the right time and in an appropriate manner. METHOD: This paper
      presents examples of difficult PBL situations using short film sequences to
      demonstrate and comments on potential approaches of the tutor in attempting to
      resolve the problem. Standard problem situations within a PBL tutorial were
      defined and produced in a film. RESULTS: A collection of seven frequent critical
      PBL situations are presented in short film sequences. Potential instruments of
      intervention are demonstrated in the videos and discussed. The film sequences may
      be downloaded in the supplementary of the electronic version of this article
      (www.sciencedirect.com). CONCLUSION: Within the framework of a tutor-training
      programme, the problematic situations and interventions presented in this article
      will help to sensitise tutors to potentially critical PBL tutorial situations and
      aid the development of individual resolution approaches.

PMID- 19402351
TI  - [Role playing as an essential element of simulation procedures in medicine].
AB  - Role playing is an important element of virtually all simulation-based
      procedures. An improved understanding for methodological aspects facilitates its
      goal-oriented use in education and training, research and examinations. In the
      present paper we describe how different forms of role play are used in different
      simulation-based procedures. We describe a plausibility study from skills labs
      demonstrating that the introduction of role-playing can increase perceived
      realism. Finally we derive practical suggestions for the conduction of role plays
      in medical simulation.

PMID- 19402352
TI  - [Virtual patients in medical education: a comparison of various strategies for
      curricular integration].
AB  - INTRODUCTION: E-Learning applications are an integral part of modern medical
      curricula. Nevertheless, there is only a narrow empirical basis for an optimal
      integration strategy of computerized teaching methods in medical education. This
      article focuses on the integration experiences with three different online
      systems for interactive virtual patients (VPs) in clinical undergraduate medical
      education at the universities of Heidelberg, Munich (LMU), and Wuerzburg.
      METHODS: Five different integration strategies for VPs are presented and compared
      with respect to motivational aspects, logistics and acceptance of both students
      and teachers. RESULTS: A voluntary use of VPs without curricular integration
      leads to low acceptance. Exam relevance of VPs and integration with face-to-face
      teaching are key factors for a high level of acceptance. The assets and drawbacks
      of all described strategies are discussed in the conclusions of this article.
      CONCLUSIONS: Case-based e-learning can be successfully integrated into clinical
      undergraduate medical education when key factors are considered.

PMID- 19402353
TI  - [Final-year medical students as tutors for undergraduate students during their on
      ward courses in internal medicine: a quantitative analysis].
AB  - INTRODUCTION: Peer-assisted learning is a common feature of medical education and
      proves to be highly effective in many areas. So far there have been no reports on
      on-ward tutorials held by final-year students to promote the clinical
      competencies of medical undergraduates. The aim of the current investigation was
      to both evaluate undergraduate and tutor acceptance of a peer-assisted learning
      programme performed by final-year students and to examine the perception of the
      role of final-year students within an intervention and a control group. METHOD:
      88 medical students (51 female, 37 male; mean age 23.6 years) were assigned to
      one of seven intervention wards where 10 student-led, patient-centred tutorials
      were held. 80 medical students (58 female, 22 male; mean age 23.3 years) were
      assigned to one of seven control wards. Tutorials were held by 14 volunteer final
      year student tutors (8 female, 6 male; mean age 26.2 years). Acceptance of the
      peer-assisted learning programme and ratings of the role of final-year students
      were evaluated on a six-point Likert scale (ranging from 1 = very good to 6 =
      unsatisfactory and 1 = completely agree to 6 = completely disagree). RESULTS:
      Medical undergraduates rated student-led tutorials and tutors rated the
      introductory course and the complete programme as extremely positive (1.14 +/-
      0.36 to 2.34 +/- 1.15). The role of final-year students as role model, teacher,
      contact person and integrator was rated as being significantly more relevant by
      students in the intervention group than by those in the control group (p < 0.02
      in each case). DISCUSSION: Patient-centred, student-led on-ward tutorials
      designed to promote undergraduate clinical competencies received extremely
      positive ratings from both medical undergraduates and tutors and enable final
      year tutors to assume important roles.

PMID- 19402354
TI  - [The evaluation of teaching at medical schools in Baden-Wuerttemberg].
AB  - This article offers an overview of options for the evaluation of medical
      education. After discussing theoretical and methodological issues we describe how
      medical education is currently being evaluated by medical faculties in Baden
      Wuerttemberg, Germany.

PMID- 19402355
TI  - [Quality assurance of assessments using the example of the OSCE examination
      format: experiences of the Medical School of Heidelberg University].
AB  - Quality management of assessment in medical education plays a key role in Germany
      -owing to, among other factors, the new medical licensing regulations
      ("Approbationsordnung"). OSCE (Objective Structured Clinical Examination) is a
      widespread tool to assess clinical competencies. However, the quality of OSCE in
      terms of reliability as a criterion of a good test is highly debated in the
      current literature. To improve the reliability of the OSCE three accompanying
      measures have been implemented at the Faculty of Medicine of the University of
      Heidelberg since the summer of 2006: 1. the application of a checklist for pre-
      and post-reviews of OSCEs, 2. a specific training of OSCE examiners, 3. an
      advanced psychometric OSCE test report giving feedback to the item developer. The
      reliability of the Internal Medicine OSCE at the University of Heidelberg has
      increased since. Currently Cronbach's alpha of the final OSCE in the summer of
      2007 was 0.829.

PMID- 19402356
TI  - [First medical assistance].

PMID- 19402357
TI  - The relationship of child neglect and physical maltreatment to placement outcomes
      and behavioral adjustment in children in foster care: a Canadian perspective.
AB  - Dramatic increases in child welfare rates in Canada over recent years have been
      largely driven by an increased reporting of neglect cases (Trocme, Fallon,
      MacLaurin, & Neves, 2005). To a large extent, exploring the importance of neglect
      separate from physical maltreatment has been ignored in the child maltreatment
      literature. This study examined the differential effects of foster care in the
      child welfare system with children who presented as either experiencing physical
      maltreatment or neglect prior to their admission to care. Findings from this
      study are important to child welfare decision making about the differential needs
      of these two groups of children. The files of a sample of 110 children (79
      neglected children and 31 physically maltreated children) were examined for
      differences in their adjustment while in foster care and on discharge. Some
      distinct differences in presentation were noted between the children experiencing
      the two types of maltreatment. Children experiencing neglect were younger, were
      more likely to have caregivers diagnosed with a substance abuse disorder, and had
      higher rates of exposure to spousal violence than maltreated children. Physically
      maltreated children displayed greater difficulty during their foster care
      adjustment. Once discharged from care, neglected children were more likely to be
      returned to the care of the agency. This study draws attention to the
      differential needs of children who experience neglect prior to their admission to
      a child welfare agency. Longer-term outcome studies are necessary to more
      completely understand how these two types of maltreatment influence the outcomes
      of children who are provided care within the child welfare system.

PMID- 19402359
TI  - The Parent-Child Home Program in Western Manitoba: a 20-year evaluation.
AB  - This article is a 20-year evaluation of the Parent-Child Home Program (PCHP) of
      Child and Family Services in Western Manitoba. Following Levenstein's (1979,
      1988) approach, home visitors model parent-child interchanges using books and
      toys to enhance children's cognitive development through appropriate parenting
      behaviors. The evaluation provides a profile of PCHP families (N = 185) and
      performance outcomes. Findings show impressive gains in cognitive competence and
      parenting behaviors. Recommendations are given for program development and future
      research.

PMID- 19402360
TI  - Planning and evaluating child welfare training projects: working toward a
      comprehensive conceptual model.
AB  - Training is widely believed to be an important element in promoting good child
      welfare practice. Scholarly attention to training, however, has been limited. To
      facilitate further development of child welfare training, in this article, we
      discuss the importance of conceptualization in the design and evaluation of
      training projects, offer a conceptual model developed for a national evaluation
      project, and suggest modifications to the model for further use in other
      settings.

PMID- 19402358
TI  - Cascading implementation of a foster and kinship parent intervention.
AB  - Most foster parents in the United States are required to participate in training,
      yet no empirical support exists for the training's effectiveness. During the past
      two decades, high-quality clinical trials have documented that parent management
      training (PMT) programs produce positive outcomes for children and families in
      clinical and school settings; yet, these advances have not transferred to
      foster/kinship parents. Here, we describe a randomized control trial testing the
      effectiveness of a PMT-based treatment with 700 foster/kinship parents in San
      Diego County. The collaborative processes to engage stakeholders, the strategies
      for involving parents, and the results of two levels of developer involvement in
      training and supervision on child behavioral outcomes are also described.

PMID- 19402361
TI  - Impact of intensive family preservation services on disproportionality of out-of
      home placement of children of color in one state's child welfare system.
AB  - This study examines the impact of intensive family preservation services (IFPS)
      on racial disproportionality of placement into out-of-home care. A large sample
      (N = 30,060) was partitioned on the basis of race, risk, and services received.
      The probability of placement is examined as a function of these variables. High
      risk minority children receiving traditional services are at higher risk of
      placement than white children are, but minority children receiving IFPS are less
      likely to be placed than white children are. When only minority children are
      examined, those receiving IFPS are less likely to be placed than those receiving
      traditional services are. IFPS is associated with a reduction in racial
      disproportionality of out-of-home placement among high-risk families. Within-race
      analysis suggests that IFPS may mitigate racial disparity in out-of-home
      placement existing in the remainder of the child welfare population that receives
      traditional services.

PMID- 19402362
TI  - Placement history of foster children: a study of placement history and outcomes
      in long-term family foster care.
AB  - The files of 419 children in family foster care and kinship foster care were used
      in a retrospective longitudinal design study that examined their placement
      histories in child welfare. Significant associations were found between the
      number of placements on one hand, and the prevalence of attachment disorders,
      severity of behavioral problems, and breakdowns of new foster care placements on
      the other hand. It appears that a breakdown can be predicted to a certain extent,
      the implications of which are discussed.

PMID- 19402363
TI  - The impact of child and family service reviews on knowledge management.
AB  - This article uses knowledge management as a framework to analyze the impact of
      the child and family review process on child protective service agencies. Results
      of a qualitative analysis of child and family service reviews and program
      improvement plans indicated that the process has led to an increase in the use of
      family team meetings and risk assessment tools as ways of managing information
      and increasing knowledge.

PMID- 19402364
TI  - Evaluation of the GERD Impact Scale, an international, validated patient
      questionnaire, in daily practice. Results of the ALEGRIA study.
AB  - BACKGROUND AND STUDY AIMS: Gastroesophageal reflux disease (GERD) is a common
      chronic disease that is primarily diagnosed based on symptom severity and
      frequency. This study gathered epidemiological data in a population of GERD
      patients and evaluated the added-value of the GERD Impact Scale (GIS), a novel,
      validated patient questionnaire, as a tool for initial and long-term patient
      management. PATIENTS AND METHODS: This observational study recruited patients
      (296 study centers) with symptomatic GERD and a history of erosive, or reflux,
      esophagitis. Symptoms were assessed by GIS and physician-subject interview and
      recorded at baseline (visit 1), at 4-6 weeks (visit 2) and 8-14 weeks (visit 3);
      also recorded at each visit was the physician's assessment of GERD severity and
      treatment changes. Analyses were performed on an intent-to-treat basis. RESULTS:
      Subjects (n = 1919; mean age, 55 years) were 54% female. Lifestyle
      characteristics included stress (approximately 70% of subjects), mean daily
      consumption of five cups of caffeine-containing beverages (approximately 70%),
      alcohol consumption of approximately nine units per week (approximately 50%) and
      smoking/ex-smoker (41%). Proton pump inhibitors were prescribed in 99% of cases:
      mainly esomeprazole (82%), with a median dose of 40 mg. Prescribed therapy was
      changed (mainly dosage levels) between visits in approximately 60% of subjects.
      The severity of GERD symptoms and GIS scores decreased substantially throughout
      the study. Mean GIS scores correlated positively with increasing GERD severity
      and clinical judgment at all visits. Physicians reported that the GIS helped them
      define the appropriate treatment for the patient and to evaluate the patient's
      response to treatment in 81% of cases. CONCLUSIONS: This study demonstrates the
      added-value and usefulness of the patient self-assessment GIS as a management
      tool for GERD.

PMID- 19402365
TI  - Role of vasoactive substances and cellular effectors in the pathophysiology of
      cirrhotic portal hypertension: the past, the present and the future--Georges
      Brohee Lecture.
AB  - In the last decade, knowledge regarding mechanisms involved in the pathogenesis
      of portal hypertension has taken unprecedented levels. However, many aspects
      still remain to be elucidated. Portal hypertension is primarily caused by an
      increase in resistance to portal outflow and secondly by an increase in
      splanchnic blood flow. In a later phase, these changes lead to a hyperdynamic
      circulation with increased cardiac output and decreased systemic vascular
      resistance and perfusion pressure. Regional alterations in vasoreactivity
      (vasodilation and vasoconstriction) play a central role in the pathophysiology of
      portal hypertension by contributing to increased intrahepatic resistance,
      hyperdynamic circulation, and expansion of the collateral circulation. Among
      vasoactive substances activated in portal hypertension, nitric oxide (NO) is
      considered as the most important vasodilator. Endothelin-1 and cyclooxygenase
      derived prostaglandins are the foremost vasoconstrictor factors. The imbalance
      between the hyperresponsiveness and overproduction of vasoconstrictors and the
      hyporesponsiveness and impaired production of vasodilators are the main
      responsible of the increased vascular one in the sinusoidal area of the liver. In
      addition to an imbalance in vasoactive substances, a major role has been
      attributed to activated hypercontractile hepatic stellate cells which cause
      vascular remodelling as an adaptive response to the changed balance in vasoactive
      substances. The present paper aims to elucidate on available knowledge and novel
      mechanisms gathered over the last years with regard to cirrhotic portal
      hypertension and the increased intrahepatic vascular resistance in particular.

PMID- 19402366
TI  - Quality assurance and recommendations for quality assessment of screening
      colonoscopy in Belgium.
AB  - As population-wide screening for colorectal cancer is adopted by many western
      countries for all individuals aged 50-75. The success of screening colonoscopy
      programs is highly dependent on the quality of the procedures. High-quality
      complete endoscopy with excellent patient preparation and adequate withdrawal
      time is necessary for effectively reducing colon cancer risk. In Belgium formal
      quality assurance programs and principles of credentialing do not exist. The
      current reimbursement system for colonoscopy does not reward a careful performed
      examination but rapidly performed examinations at unnecessarily short intervals.
      There is a clear need for evidence-based quality measures to ensure the quality
      of screening colonoscopy. In this guideline review we present an overview of the
      literature concerning criteria for best practice and important quality indicators
      for colonoscopy. A summary of the latest guidelines is given. Our goal of this
      update is to provide practical guidelines for endoscopists performing screening
      colonoscopy. We hope to provide a broad consensus and an increasing adherence to
      these recommendations.

PMID- 19402367
TI  - Management of gastro-entero-pancreatic neuroendocrine tumours (GEP NET): an
      introduction.

PMID- 19402368
TI  - Diagnostic pitfalls in digestive neuroendocrine tumours.
AB  - Gastro-entero-pancreatic neuroendocrine tumours (GEP NET) represent a rare and
      highly heterogeneous entity that often is revealed by vague and non-specific
      symptoms, leading to a delayed diagnosis. Here we will review some of the most
      regularly observed false positive and false negative cases and provide clues to
      recognize and manage them properly. Particularly, the value of chromogranin-A as
      a serum tumour marker and Somatostatin receptor scintigraphy as an imaging test,
      are reviewed. Indeed, chromogranin-A and other hormones, such as gastrin, as well
      as urinary 5-hydroxy-indolic acetic acid (5-HIAA) are often tested to diagnose
      NET without appraising the clinical situation, leading to extensive work-up on
      false bases. On the other hand, some tests are performed in situations where they
      do not add additional information (e.g. 5-HIAA in pancreatic or rectal NET)
      because invariably negative. Somatostatin receptor scintigraphy is an expensive
      examination, still not reimbursed in Belgium, for which indications must be
      carefully assessed, knowing its specificity and sensitivity.

PMID- 19402369
TI  - Carcinoid heart disease--a hidden complication of neuroendocrine tumours.
AB  - Carcinoid heart disease (CHD) develops in serotonin-producing neuroendocrine
      tumours (NET) due to fibrotic endocardial plaques with associated valve
      dysfunction leading most often to right-sided heart failure. The classical
      carcinoid syndrome usually occurs when serotonin-producing NET metastasize to the
      liver. Up to 50% of those patients will exhibit carcinoid heart disease. The
      pathophysiological process is not yet completely understood: serotonin is
      considered to be a major initiator of the fibrotic process, but other tumour
      secreted factors may contribute to the pathogenesis. Histopathology reveals
      intact valvular cusps with superimposed fibrotic plaques, leading to thickening
      and retraction of the valves, causing valvular dysfunction. A high index of
      clinical suspicion to diagnose CHD is needed since symptoms can be rather non
      specific. Transthoracic echocardiography is the gold standard for diagnosis and
      should probably be performed at the time of diagnosing serotonin-producing NET
      and then repeated annually. On the other hand, when diagnosing right-heart
      failure, the presence of CHD and underlying serotonin-producing NET should be
      taken into account. Therapeutic options include pharmacotherapy for heart
      failure, control of the systemic carcinoid disease and in selected individuals
      cardiac valve replacement. The elucidation of the pathologic process is necessary
      to develop targeted antifibrotic therapeutic agents since CHD seems to be
      irreversible and associated with poor prognosis.

PMID- 19402370
TI  - The role of surgery and transplantation in neuroendocrine tumours.
AB  - Surgery represents the only chance of cure for a patient with a neuroendocrine
      tumour (NET). The main indications for surgery lie in the risk of developing
      metastatic disease with increasing tumour diameter and for a functioning NET also
      in control of the hormonal syndrome. However, only a small minority of patients
      presents with a potentially resectable primary NET without metastatic disease. An
      R0-resection is mandatory, which may be achieved in selected cases by tissue
      sparing surgical techniques. Most patients unfortunately present with a locally
      advanced or metastatic disease. For patients with an advanced functioning NET,
      control of the hormonal syndrome may also represent a surgical indication.
      Various cytoreductive techniques or, in highly selected cases, liver
      transplantation can be applied. For locally advanced non-functioning tumours,
      there is an indication for surgery in large tumours which tend to create local
      complications because of bleeding or bowel obstruction. Especially in ileal NETs
      aggressive surgical therapy is recommended because of prevention of long-term
      complications, which may improve survival.

PMID- 19402371
TI  - Locoregional and radioisotopic targeted treatment of neuroendocrine tumours.
AB  - Gastro-entero-pancreatic neuroendocrine tumours (GEP NET) are a heterogeneous
      group of proliferative disorders whose management dramatically relies on tumour
      biology. For well-differentiated, low-proliferative index tumours, locoregional
      treatment and targeted radioisotopic therapies offer an attractive and seemingly
      efficient alternative to palliative surgical resections. Lack of well-designed,
      prospective, randomized multicentric studies hinders a balanced evaluation of
      available locoregional treatment methods: embolization, chemo-embolization, radio
      embolization. According to available datas, all techniques achieve a 50-60%
      radiological response rate and almost 80% of symptomatic relieve for the
      patients, while their impact on progression-free and overall survival remains not
      assessable. Same conclusions can be drawn for radiolabeled targeted therapies
      like MetaiodoBenzylGuanidine (MIBG) and Peptide Receptor Radionuclide Therapy
      (PRRT), which, provided that their target is expressed by tumour cells, can
      deliver therapeutic doses of radiation to neoplastic tissues. 131I-MIBG has been
      associated with a 50% symptomatic response rate and mainly haematological
      toxicities. PRRT with 111In-DiethyleneTriamineentaacetic Acid-Octreotide, [90Y
      DOTA0-Tyr3]-Octreotide, or [177Lu-DOTA0-Tyr3]-Octreotate seem to alleviate
      symptoms in 50% of patients and obtain a radiological response in 30-38%. Renal
      toxicity, partially preventable, is more frequent than previously thought and
      result in an annual decrease in glomerular function by 4 to 8% per year.
      Forthcoming research in GEP NET should by a majority be designed in randomized,
      prospective and multicentric fashion. Locoregional disease trials must focus on
      clinical outcome differences between embolization techniques (embolization,
      chemoembolization and radioembolization) and surgery. In disseminated disease,
      studies should assess radiolabeled targeted therapies efficiency when
      administered along with and compared to new biological and older chemotherapeutic
      agents.

PMID- 19402372
TI  - Role of chemotherapy in gastro-entero-pancreatic neuroendocrine tumors: the end
      of a story?
AB  - Gastroenteropancreatic Neuroendocrine Tumours (GEP NET) are heterogeneous and
      rare malignancies although their prevalence is increasing. Multiple therapeutic
      approaches are available to date for their management, including surgery,
      hormonal and immune radionucleide therapies and chemotherapy. The purpose of this
      review is to collect, examine, and analyze data available regarding contemporary
      chemotherapeutic management of GEP NET in order to determine whether or not
      chemotherapy still takes place in the therapeutic arsenal of GEP NET. We
      therefore performed a systematic search of all the English-spoken literature
      regarding GEP NET. Anthracyclins, 5-fluorouracil (5-FU), DTIC and streptozotocin
      are amongst the most commonly used chemotherapeutic agents, usually prescribed in
      combination. Their efficiency in reducing tumor burden is not always associated
      with better survival, perhaps due to severe toxicity. Chemotherapy in GEP NET is
      mainly devoted to poorly differentiated tumours, but also in well differentiated
      carcinomas either not eligible or resistant to other therapies. Chemotherapy
      remains therefore useful in specific cases of GEP NET management. However, a new
      era of antitumoral agents, such as targeted therapies, could eventually replace
      these old recipes in the near future.

PMID- 19402373
TI  - The antiproliferative effect of somatostatin analogs: clinical relevance in
      patients with neuroendocrine gastro-entero-pancreatic tumours.
AB  - Somatostatin analogs (SSAs) have an important role in the management of patients
      with neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP
      NETs). These compounds can control the symptoms induced by the production of
      hormones and peptides. The antiproliferative effects of SSAs and especially
      tumour shrinkage are less obvious in patients with GEP NETs than in those with
      acromegaly. However, based upon phase II experience there is a strong suggestion
      of a disease stabilizing effect of SSAs in selected patients. Those patients with
      a progressive, non-functional GEP NET, positive octreotide scintigraphy, a low
      proliferation index and in the absence of surgical options may benefit from a
      first-line medical therapy with SSAs. The exploration of the mechanisms of this
      effect are unclear and hampered by the lack of suitable preclinical models. The
      better understanding of the tumour biology of GEP NETs, together with the
      development of new SSAs with better affinity on all somatostatin receptors,
      represent an unmet medical need.

PMID- 19402374
TI  - The potential role of targeted therapies in the management of neuroendocrine
      tumours.
AB  - The management of gastro-entero-pancreatic neuroendocrine tumours is evolving
      thanks to new TNM-classification, diagnostic and staging procedures and new
      therapeutic options. Targeting new pathways, mostly angiogenesis, development of
      novel agents is under way and opens new perspectives in controlling the evolution
      of these tumours and possibly changing their management. In parallel, new
      functional imaging techniques and biomolecular markers will be developed to
      provide adequate tools for the assessment of tumor response according to
      therapeutic intervention on angiogenesis, proliferation and apoptosis. This paper
      reviews the potential role of new investigational targeted agents which will
      likely become the backbone of future therapy of neuroendocrine tumors.

PMID- 19402376
TI  - Experts say sales training essential.

PMID- 19402377
TI  - Small changes, big rewards.

PMID- 19402375
TI  - Single brain metastasis from a minute, well differentiated, but invading beyond
      the tunica muscularis mucosa rectal carcinoid.
AB  - We report the case of a 48-year-old woman with small-sized (< 10 mm), highly
      differentiated, aggressive rectal carcinoid, who developed a solitary distant
      metastasis to the brain. The primary lesion, initially removed by conventional
      polypectomy, invaded the mucosa/tunica muscularis mucosa and had positive
      resection margins. Afterwards, an assessment of 5-hydroxyindoloacetic acid (5
      HIAA) 24 h urine excretion revealed a significantly increased level. Thus, a
      partial rectal resection was performed. Because of constantly elevated carcinoid
      markers: serum chromogranin A (CGA) and 5-HIAA, a somatostatin receptor
      scintigraphy was performed, which disclosed a focus of pathological marker
      accumulation in the left frontal area. The pathological finding after
      neurosurgical excision was meningioma. An unexpected normalization of the
      biochemical markers prompted us to verify this diagnosis. The final
      histopathological report was a well-differentiated neuroendocrine brain
      metastasis. Our case shows that in well differentiated, of diameter < 10 mm
      rectal carcinoids, an invasion even beyond the mucosa/tunica muscularis mucosa
      seems to be an independent factor predicting a malignant metastatic potential of
      these tumors. Hence, in such cases, behind the endoscopic submucosal resection
      with ligation device a more radical surgery should be considered. Additionally, a
      systematic CGA and 5-HIAA follow-up assessment and whole body somatostatin
      receptor scintigraphy, if necessary, are required.

PMID- 19402378
TI  - LTC provider plays role in HIE development.

PMID- 19402379
TI  - How to avoid staff discrimination.

PMID- 19402380
TI  - Putting patient safety first.

PMID- 19402381
TI  - Long term care school earns high marks.

PMID- 19402382
TI  - Karyometry: correction algorithm for differences in staining.
AB  - OBJECTIVE: To describe an algorithm that allows the correction of differences in
      staining of histopathologic sections while preserving chromatin texture. STUDY
      DESIGN: In order to preserve the texture of the nuclear chromatin in the
      corrected digital imagery, it is necessary to correct the images pixel for pixel.
      This is accomplished by mapping each pixel's value onto the cumulative frequency
      distribution of the data set to which the image belongs, to transfer to the
      cumulative frequency distribution of the data set serving as standard and to
      project the intersection down onto the pixel optical density scale for the
      corrected value. RESULTS: Feature values in the corrected imagery, for the
      majority of features used in karyometry, are between < 1% and a few percent of
      the feature values in standard imagery. For some higher-order statistical
      features involving multiple pixels, sensitivity to a shift in the cumulative
      frequency distribution may exist, and a secondary small correction by a factor
      may be required. CONCLUSION: The correction algorithm allows the elimination of
      the effects of small staining differences on karyometric analysis.

PMID- 19402383
TI  - Expression of immunomodulating genes in prostate cancer and benign prostatic
      tissue.
AB  - OBJECTIVE: To investigate the expression of immunomodulating genes in prostate
      cancer and benign prostatic tissue. STUDY DESIGN: We investigated by quantitative
      real-time polymerase chain reaction the expression of indoleamine 2,3
      dioxygenase, arginase 1, arginase 2, inducible form of nitric oxide synthase,
      cyclooxygenase 2 (COX-2), programmed death ligand 1 and interleukin 10 in 36
      matched pairs of samples from prostate cancer and benign prostatic tissue.
      RESULTS: Among the genes analyzed, arginase 2 and COX-2 showed statistically
      significant up-regulation and down-regulation, respectively, in malignant
      compared to benign prostate tissue. In addition, arginase 1 was more often
      present in cancer than benign samples. No significant modulation was detected for
      the other genes under investigation. CONCLUSION: Our data suggest that arginine
      metabolism may be involved in prostate cancer immune response evasion, whereas
      COX-2 may play a role in pathogenesis. We provide a snapshot of immunosuppressive
      gene expression at the transcriptional level in the prostate tumor
      microenvironment.

PMID- 19402384
TI  - Automatic segmentation of cell nuclei in bladder and skin tissue for karyometric
      analysis.
AB  - OBJECTIVE: To automatically segment cell nuclei in histology images of bladder
      and skin tissue for karyometric analysis. STUDY DESIGN: The 4 main steps in the
      program were as follows: median filtering and thresholding, segmentation,
      categorizing and cusp correction. This robust segmentation technique used
      properties of the image histogram to optimally select a threshold and create
      closed 4-way chain code nuclear segmentations. Each cell nucleus segmentation was
      treated as an individual object of which the properties of segmentation quality
      were used for criteria to classify each nucleus as: throw away, salvageable or
      good. An erosion/dilation procedure and rethresholding were performed on
      salvageable nuclei to correct cusps. RESULTS: Ten bladder histology images were
      segmented both by hand and using this automatic segmentation algorithm. The
      automatic segmentation resulted in a sensitivity of 76.4%, defined as the
      percentage of hand-segmented nuclei that were automatically segmented with good
      quality. The median proportional difference between hand and automatic
      segmentations over 42 nuclei each with 95 features used in karyometric analysis
      was 1.6%. The same procedure was performed on 10 skin histology images with a
      sensitivity of 83.0% and median proportional difference of 2.6%. CONCLUSION: The
      close agreement in karyometric features with hand segmentation shows that
      automated segmentation can be used for analysis of bladder and skin histology
      images.

PMID- 19402386
TI  - Validation of cytopathology as a technique for analysis of epithelial cell
      maturation in oral mucosa of smokers and nonsmokers.
AB  - OBJECTIVE: To validate quantitative analysis of epithelial cells in oral mucosa
      smears of smokers and nonsmokers. STUDY DESIGN: Sixty samples from the oral
      mucosa of 10 smokers and 10 nonsmokers were collected from the anatomic sites
      more frequently affected by oral cancer: lower lip, border of the tongue and
      floor of the mouth. Slides were stained using Papanicolau and Traut techniques;
      anucleated squamous, nucleated superficial and intermediate cells were counted.
      RESULTS: The first 50, the first 100 and all nonoverlapping cells on the slide
      were counted. To compare percentages of cell types, Pearson's correlation
      coefficient was used. In the first 50 cells analyzed, there was no significant
      correlation for anucleated cells in lower lip samples of smokers and border of
      the tongue samples of nonsmokers; for the other types of cells, a significant
      correlation was found. For the first 100 cells analyzed, all types of cells in
      the 3 anatomic sites showed a significant correlation, both in smokers and
      nonsmokers. CONCLUSION: The quantification of the first 100 cells proved to be
      sufficient to evaluate the epithelial maturation pattern in smears of the lower
      lip, border of the tongue and floor of the mouth of smokers and nonsmokers.

PMID- 19402387
TI  - Comparative genomic hybridization-based oncogenetic tree model for genetic
      classification of breast cancer.
AB  - OBJECTIVE: To describe a genetic progression pathway in breast cancer by a
      maximum likelihood-based tree model representing the dependencies between
      chromosomal imbalances. STUDY DESIGN: One hundred six cases were studied by
      comparative genomic hybridization, followed by maximum likelihood estimation of
      an oncogenetic tree model. RESULTS: The tree model identified 3 clusters with
      correlated chromosomal imbalances. The first cluster included losses at 4q, 5q,
      6q, 9p, 13q and a gain at 17q; the second cluster included gains at 1q, 8q, 16p
      and 20q; the third cluster included losses at 8p, 11q, 16q and 18q. The
      imbalances nearest the root of the tree were the loss at 13q (cluster 1), the
      gain at 1q (cluster 2) and the loss at 18q (cluster 3), reflecting an early
      change in breast cancer evolution. Cox regression analysis revealed the tumor
      stage and the grade as relevant for overall survival (p = 0.001) and the tumor
      stage, the grade and the loss at 16q as relevant for disease-free survival (p =
      0.001). CONCLUSION: Methods like oncogenetic tree analysis provide insights into
      the genetic progression of breast cancer and may extract relevant markers
      detected by screening methods like comparative genomic hybridization for further
      studies.

PMID- 19402388
TI  - Renal papillary carcinoma classification into subtypes may be reproduced by
      nuclear morphometry.
AB  - OBJECTIVE: To analyze relationships between nuclear features of papillary renal
      cell carcinoma (PapRCC) subtypes. STUDY DESIGN: The material for the study
      consisted of 53 cases, of which 29 were type 1, 17 type 2 and 7 intermediate. At
      least 100 nuclei per case were segmented from images of 4',6-diamidino-2
      phenylindole-stained slides. The geometric and texture features were extracted
      and used for analysis. RESULTS: In analysis of variance, it was shown that both
      individual cases and tumor types differ in the majority of the parameters. On
      nonsupervised expectation-maximization clustering, it was possible to classify
      the nuclei into separate categories, but PapRCC classes were not reproduced. The
      neural network classified the nuclei with sensitivity >0.6 and specificity >0.75.
      Analyzing the results for individual cases, the nuclei of type 1 cases were
      properly classified in 74-91%, nuclei of type 2 cases in 58-80% and nuclei of
      intermediate cases in 53-70%. CONCLUSION: Our findings show that PapRCC subtypes
      are distinct enough to be reproduced by image analysis.

PMID- 19402389
TI  - Diagnostic and prognostic impact of p63 immunoreactivity in renal malignancies.
AB  - OBJECTIVE: To determine the ability of p63 reactivity to confirm the diagnosis of
      urothelial carcinomas (UCs) that present clinically as kidney masses and to
      determine the association of p63 expression with clinicopathologic features in
      UCs. STUDY DESIGN: The study included 27 patients with renal pelvis UC and 42
      patients with renal cell carcinoma (RCC). p63 Reactivity was examined
      immunohistochemically in tumor and nonneoplastic tissues. Correlation of p63
      expression in renal malignancies (RCCs and UCs) was investigated and compared
      with clinicopathologic parameters. RESULTS: p63 Expression was detected in 25 of
      27 (92.6%) UC cases while none of the RCC cases were positive for p63. There was
      a correlation between p63 expression and tumor stage, grade and survival time (p
      < 0.0001, = 0.032, = 0.028, respectively). However, no correlation was found
      between p63 expression and tumor progression (p = 0.513). CONCLUSION: p63 Should
      be considered as an additional biomarker to distinguish UC from RCC. Decreased
      p63 immunoreactivity was significantly associated with advanced tumor stage and
      grade. p63 Reactivity appears to be a useful prognostic factor in UC.

PMID- 19402390
TI  - Dr. Donald Floyd Gleason's historic, immense contribution to urologic pathology.

PMID- 19402391
TI  - Optical monitoring of particle aggregates.
AB  - Methods for monitoring particle aggregation are briefly reviewed. Most of the
      techniques are based on some form of light scattering and may be greatly
      dependent on the optical properties of aggregates, which are not generally known.
      As fractal aggregates grow larger their density can become very low and this has
      important practical consequences for light scattering. For instance, the
      scattering coefficient may be much less than for solid objects, which means that
      the aggregates can appear much smaller than their actual size by a light
      transmission method. Also, for low-density objects, a high proportion of the
      scattered light energy is within a small angle of the incident beam, which may
      also be relevant for measurements with aggregates. Using the "turbidity
      fluctuation" technique as an example, it is shown how the apparent size of
      hydroxide flocs depends mainly on the included impurity particles, rather than
      the hydroxide precipitate itself. Results using clay suspensions with hydrolyzing
      coagulants and polymeric flocculants under different string conditions are
      discussed.

PMID- 19402392
TI  - The effect of coupling coagulation and flocculation with membrane filtration in
      water treatment: a review.
AB  - Water supply and sanitation demands are foreseen to face enormous challenges over
      the coming decades to meet the fast growing needs in a global perspective.
      Significant growth in the industry is predicted and membrane separation
      technologies have been identified as one of the possible solutions to meet future
      demands. Application and implementation of membrane technology is expected both
      in production of potable water as well as in treatment of wastewater. In potable
      water production membranes are substituting conventional separation technologies
      due to the superior performance, potential for less chemical use and sludge
      production, as well as the potential to fulfill hygienic barrier requirements.
      Membrane bio-reactor (MBR) technology is probably the membrane process which has
      had most success and has the best prospects for the future in wastewater
      treatment. Trends and developments indicate that this technology is becoming
      accepted and is rapidly becoming the best available technology for many
      wastewater treatment applications. A major drawback of MBR systems is membrane
      fouling. Studies have shown that fouling mitigation in MBR systems can
      potentially be done by coupling coagulation and flocculation to the process.

PMID- 19402393
TI  - Effectiveness of fluidized pellet bed for removing soluble contaminants.
AB  - Fluidized pellet bed (FPB) has been successfully applied in water and wastewater
      treatment. However, the removal mechanism of contaminants especially the soluble
      ones, is still unclear. This study aimed to evaluate the effectiveness of FPB
      reactor for removing soluble contaminants from synthetic wastewater. By only
      coagulation through jar test operation with addition of polyaluminium chloride
      (PACl) as primary coagulant and polyacryamide (PAM) as coagulant-aid, the
      removals of soluble chemical oxygen demand (COD), total phosphorus (TP), and NH4+
      -N were found to be only 2.2%-7.5%, 5.7%-25.5%, and 9.9%-18.5%, respectively.
      However, by FPB operation under the same dosage of coagulants, these values
      increased to 82.7%, 37.2%, and 50%, indicating that the formation of pellets in
      the FPB effectively enhanced the removal of soluble contaminants. By careful
      comparison of the settleablility and filterability of the pollutants after
      coagulation, the originally soluble contaminants could be divided into three
      groups, namely: (1) coagulated-and-settleable, (2) coagulated-but-nonsettleable,
      and (3) uncoagulable. It was found that not only the first two groups but also a
      large part of the third group could be effectively removed by FPB operation.
      However, the mechanism for the removal of the uncoagulable pollutants by FPB
      operation still needs further investigation.

PMID- 19402394
TI  - Purification and characterization of Al13 species in coagulant polyaluminum
      chloride.
AB  - Nano-Al13 was separated and purified by four methods to investigate its
      characteristic, and was analyzed by Al-Ferron timed complexation
      spectrophotometer, 27Al-NMR (nuclear magnetic resonance), and transmission
      electron microscopy (TEM). Coagulation efficiency of nano-Al13, polyaluminum
      chloride (PAC), and AlCl3 in synthetic water were also investigated by jar test.
      The dynamic process and aggregation state of kaolin suspensions coagulating with
      nano-Al13, PAC, and AICl3 were also investigated. The experimental results
      indicated that the efficiency of gel column chromatography method was the highest
      for separating PAC solution with low Al concentration. Ethanol and acetone method
      was simple and could separated PAC solution with different Al concentrations,
      while silicon alkylation white block column chromatography method could separate
      PAC solution only with low Al concentration. The SO4(2-)/Ba2+ displacement method
      could separate PAC solution with high Al concentration, but extra inorganic
      cation and anion could be introduced into the solution during the separation. The
      coagulation efficiency and dynamic experimental results showed that nano-Al13
      with a high positive-charged species was the main species of electric
      neutralization in coagulation process, and it could reduce the turbidity and
      increase the effective particles collision rate efficiently in coagulation
      process. Its coagulation speed and the particle size of coagulant formed were of
      greatest value in this study.

PMID- 19402396
TI  - Interfacial forces between silica surfaces measured by atomic force microscopy.
AB  - Colloidal particle stability and some other interfacial phenomena are governed by
      interfacial force interactions. The two well known forces are van der Waals force
      and electrostatic force, as documented by the classical Derjaguin, Landau,
      Verwey, and Overbeek (DLVO) theory. Moreover, advances in modern instrumentation
      and colloid science suggested that some short-ranged forces or structure forces
      are important for relevant colloidal systems. The interfacial and/or molecular
      forces can be measured as a resultant force as function of separation distance by
      atomic force microscopy (AFM) colloid probe. This article presents a discussion
      on AFM colloid probe measurement of silica particle and silica wafer surfaces in
      solutions with some technical notifications in measurement and data convolution
      mechanisms. The measured forces are then analyzed and discussed based on the
      'constant charge' and 'constant potential' models of DLVO theory. The difference
      between the prediction of DLVO theory and the measured results indicates that
      there is a strong short-range structure force between the two hydrophilic
      surfaces, even at extremely low ionic concentration, such as Milli-Q water purity
      solution.

PMID- 19402395
TI  - Evaluating the effects of granular and membrane filtrations on chlorine demand in
      drinking water.
AB  - In this study, chlorine decay experiments were conducted for the raw water from
      Nakdong River that is treated by Chilseo Water Treatment Plant (CWTP) situated in
      Haman, Korea as well as the effluents from sand and granular activated carbon
      (GAC) filters of CWTP and fitted using a chlorine decay model. The model
      estimated the fast and slow reacting nitrogenous as well as organic/inorganic
      compounds that were present in the water. It was found that the chlorine demand
      due to fast and slow reacting (FRA and SRA) organic/inorganic substances was not
      reduced significantly by sand as well as GAC filters. However, the treated
      effluents from those filters contained FRA and SRA that are less reactive and had
      small reaction rate constants. For the effluents from microfiltration,
      ultrafiltration, and nanofiltration the chlorine demand because FRA and SRA were
      further reduced but the reaction rate constants were larger compared to those of
      sand and GAC filter effluents. This has implications in the formation of
      disinfection by products (DBPs). If DBPs are assumed to form due to the
      interactions between chlorine and SRA, then it is possible that the DBP formation
      potential in the effluents from membrane filtrations could be higher than that in
      the effluents from granular media filters.

PMID- 19402385
TI  - The European Network of Uropathology: a novel mechanism for communication between
      pathologists.
AB  - In pathology there is a need to rapidly disseminate professional information to
      the appropriate target groups. This is a surprisingly difficult task on an
      international level. Therefore, the European Network of Uropathology (ENUP) was
      recently organized by the Uropathology Working Group of the European Society of
      Pathology. The purposes were to establish a channel for distribution of
      information about uropathology, such as guidelines, consensus documents, meetings
      and courses; to organize research collaborations; and to set up mechanisms for
      survey studies. ENUP has recruited a total of 374 individual members from 338
      pathology laboratories in 15 Western European countries. E-mail is used for all
      communication, and studies are carried out through interactive Web sites.
      Information e-mails are sent regularly, and 2 Web-based surveys on handling and
      reporting of urologic specimens have been conducted. Here we report on the
      methods used to organize this novel information network. We think that ENUP could
      serve as a model for other fields of pathology and other geographic regions.

PMID- 19402397
TI  - Removal of citrate and hypophosphite binary components using Fenton, photo-Fenton
      and electro-Fenton processes.
AB  - Both citrate and hypophosphite in aqueous solution were degraded by advanced
      oxidation processes (Fe2+/H2O2, UV/Fe2+/H2O2, and electrolysis/ Fe2+/H2O2) in
      this study. Comparison of these techniques in oxidation efficiency was
      undertaken. It was found that Fenton process could not completely degrade citrate
      in the presence of hypophosphite since it caused a series inhibition. Therefore,
      UV light (photo-Fenton) or electron current (electro-Fenton) was applied to
      improve the degradation efficiency of the Fenton process. Results showed that
      both photo-Fenton and electro-Fenton processes could overcome the inhibition of
      hypophosphite, especially the electro-Fenton.

PMID- 19402398
TI  - Fractal analysis of polyferric chloride-humic acid (PFC-HA) flocs in different
      topological spaces.
AB  - The fractal dimensions in different topological spaces of polyferric chloride
      humic acid (PFC-HA) flocs, formed in flocculating different kinds of humic acids
      (HA) water at different initial pH (9.0, 7.0, 5.0) and PFC dosages, were
      calculated by effective density-maximum diameter, image analysis, and N2
      absorption-desorption methods, respectively. The mass fractal dimensions (Df) of
      PFC-HA flocs were calculated by bi-logarithm relation of effective density with
      maximum diameter and Logan empirical equation. The Df value was more than 2.0 at
      initial pH of 7.0, which was 11% and 13% higher than those at pH 9.0 and 5.0,
      respectively, indicating the most compact flocs formed in flocculated HA water at
      initial pH of 7.0. The image analysis for those flocs indicates that after
      flocculating the HA water at initial pH greater than 7.0 with PFC flocculant, the
      fractal dimensions of D2 (logA vs. logdL) and D3 (logVsphere VS. logdL) of PFC-HA
      flocs decreased with the increase of PFC dosages, and PFC-HA flocs showed a
      gradually looser structure. At the optimum dosage of PFC, the D2 (logA vs. logdL)
      values of the flocs show 14%-43% difference with their corresponding Df, and they
      even had different tendency with the change of initial pH values. However, the D2
      values of the flocs formed at three different initial pH in HA solution had a
      same tendency with the corresponding Dr. Based on fractal Frenkel-Halsey-Hill
      (FHH) adsorption and desorption equations, the pore surface fractal dimensions
      (Ds) for dried powders of PFC-HA flocs formed in HA water with initial pH 9.0 and
      7.0 were all close to 2.9421, and the Ds values of flocs formed at initial pH 5.0
      were less than 2.3746. It indicated that the pore surface fractal dimensions of
      PFC-HA flocs dried powder mainly show the irregularity from the mesopore-size
      distribution and marcopore-size distribution.

PMID- 19402399
TI  - Fouling of nanofiltration membrane by effluent organic matter: characterization
      using different organic fractions in wastewater.
AB  - The UF membrane with molecular weight cutoff (MWCO) ranging from 2 to 100 kDa and
      XAD-8 resin were employed to identify the characteristic of molecular weight (MW)
      distribution of wastewater effluent organic matter (EfOM) in terms of TOC and
      UV254, as well as the amounts of the hydrophilic/hydrophobic organic fractions in
      different MW ranges. Then, the nanofiltration (NF) membrane fouling experiments
      were carried out using the above fractionated water to investigate the effect of
      MW distribution and hydrophilic/hydrophobic characteristics of EfOM on the
      membrane flux decline using the fractionated water samples. The experimental
      results have shown that 45.61% of the total organics belongs to the low MW one,
      among which the percentage of the hydrophilic organics with low MW (less than 2
      kDa) was up to 28.07%, while that of the hydrophobic organics was 17.54%. In
      particular, the hydrophilic fraction was found to be the most abundant fraction
      in the effluents. MW distribution has a significant effect on the membrane
      fouling. When the MW was less than 30 kDa, the lower the MW, the larger was the
      specific flux decline, while in the case of MW higher than 30 kDa, the higher the
      MW, the larger was the specific flux decline, and the decline degree of low MW
      organics was larger than the high MW one. With the same MW distribution range,
      specific flux decline of the hydrophilic organic was considerably slower than
      that of the hydrophobic organic, which indicated that the hydrophobic organic
      fractions dominantly contribute to the flux decline.

PMID- 19402400
TI  - Characterization of dissolved organic matter fractions and its relationship with
      the disinfection by-product formation.
AB  - Dissolved organic matter (DOM) has been identified as precursor for disinfection
      by-products (DBPs) formation during chlorination. Recently, it has been
      demonstrated that the characteristics of DOM influence the DBPs formation
      mechanism. A study was, therefore, initiated to investigate the effects of DOM
      fractions on DBPs formation mechanism. In the chlorination process, organic acids
      are dominant precursors of total thihalomethanes (TTHM) because of the v(c-o) and
      unsaturated structures. Furthermore, the TTHM formation of organic acids was
      affected by pH more greatly. Based on the fluorescence spectroscopy analysis, DOM
      fractions contained several fluorescence substances. During chlorination, humic
      acid-like substances were found to exhibit high chlorine reactivity and
      hydrophobic organics decomposed to smaller molecules faster than hydrophilic
      organics even at lower chlorine dosages. Unlike hydrophobic fractions,
      hydrophilic organics showed no toxicity following chlorination, suggesting that
      the toxic structures in hydrophilic organics showed high chlorine reactivity
      during chlorination.

PMID- 19402401
TI  - Persistence and growth of faecal culturable bacterial indicators in water column
      and sediments of Vidy Bay, Lake Geneva, Switzerland.
AB  - The aims of this study was to investigate the persistence and the growth of
      culturable bacterial indicators (CBI) including total coliforms (TC) and faecal
      coliforms represented by Escherichia coli, enterococcus (ENT), and aerobic
      mesophilic bacteria (AMB) in the surface sediments and the water column of Vidy
      Bay (Lake Geneva, City of Lausanne, Switzerland). The study was carried out for
      60 d using microcosms containing Sewage Treatment Plant (STP) effluent and
      nonsterile water without CBI, as well as contaminated and non-contaminated
      sediments. The effects of water temperature and of organic matter associated with
      sediments on the survival of CBI in the sediments and the water column were
      observed. The number of CBI colonies in the contaminated sediments of Vidy Bay
      and in the STP effluent was almost identical in the order of 10(5)-10(7), 10(4)
      10(6), 10(3)-10(5), and 10(4)-10(7) CFU/100 g sediment or/100 mL water for TC, E.
      coli, ENT, and AMB respectively. A degradation of CBI was observed in the
      sediments where organic matter content was low and in the water column at a
      temperature of 10 degrees C after 5 d of experimentation. In addition, a growth
      of CBI was observed in the sediment which is rich in organic matter at 20 degrees
      C. The results of this study indicate: (1) the higher concentrations of the CBI
      observed in different points in the water column of Vidy Bay may not be explained
      only by the recent contribution of the three potential sources of the Bay
      contamination including STP and the Chamberonne and Flon Rivers, but also by the
      persistence, removal from sediment and multiplication of CBI in the sediment and
      water column; (2) the sediment of Vidy Bay constitute a reservoir of CBI and can
      even support their growth; and (3) the CBI not only survive in sediments, but
      also can be remobilized and increased in the water column, therefore, it become a
      permanent microbiological pollution in Vidy Bay.

PMID- 19402402
TI  - Three-stage aged refuse biofilter for the treatment of landfill leachate.
AB  - A field-scale aged refuse (AR) biofilter constructed in Shanghai Refuse Landfill,
      containing about 7000 m3 aged refuse inside, was evaluated for its performance in
      the treatment of landfill leachate. This AR biofilter can be divided into three
      stages and can manage 50 m3 landfill leachate per day. The physical, chemical,
      and biological characteristics of AR were analyzed for evaluating the AR
      biofilter as leachate treatment host. The results revealed that over 87.8%-96.2%
      of COD and 96.9%-99.4% of ammonia nitrogen were removed by the three-stage AR
      biofilter when the influent leachate COD and ammonia nitrogen concentration were
      in the range 5478-10842 mg/L and 811-1582 mg/L, respectively. The final effluent
      was inodorous and pale yellow with COD and ammonia nitrogen below 267-1020 mg/L
      and 6-45 mg/L, respectively. The three-stage AR biofilter had efficient
      nitrification but relative poor denitrification capacity with a total nitrogen
      (TN) removal of 58%-73%. The external temperature of AR biofilter did not
      influence the total ammonia nitrogen removal significantly. It was concluded that
      the scale-up AR biofilter can work very well and can be a promising technology
      for the treatment of landfill leachate.

PMID- 19402403
TI  - Biodegradation of malathion by Acinetobacter johnsonii MA19 and optimization of
      cometabolism substrates.
AB  - To enhance the removal efficiency of malathion in the wastewater from
      organophosphate pesticide mill, a bacterium, Acinetobacter johnsonii MA19, that
      could degrade malathion with cometabolism was isolated from malathion-polluted
      soil samples using enrichment culture techniques. Four kinds of additional
      compounds, sodium succinate, sodium acetate, glucose, and fructose were tested to
      choose a favorite carbon source for the cometabolism of strain MA19. The results
      showed that sodium succinate and sodium acetate could promote malathion
      biodegradation and cell growth. The investigation results of the effects of
      sodium succinate concentrations on the malathion biodegradation indicated that
      the more sodium succinate supplied resulted in quick degradation of malathion and
      fast cells multiplied. Zero-order kinetic model was appropriate to describe the
      malathion biodegradation when the concentration of sodium succinate was more than
      0.5144 g/L. The degradation rate constant (K) reached the maximum value of 3.5837
      mg/(L x h) when the mass ratio of sodium succinate to malathion was 128.6 mg/mg.
      The aquatic toxicity of the malathion was evaluated using the test organism,
      Limnodrilus hoffmeisteri. The data obtained suggested that the toxicity of
      malathion could be ignored after 84 h biodegradation. Our result demonstrates the
      potential for using bacterium A. johnsonii MA19 for malathion biodegradation and
      environmental bioremediation when some suitable conventional carbon sources are
      supplied.

PMID- 19402404
TI  - Effect of proteins, polysaccharides, and particle sizes on sludge dewaterability.
AB  - Four batch experiments of hydrolysis and acidification were carried out to
      investigate the distributions of proteins (PN) and polysaccharides (PS) in the
      sludge, the PN/PS ratio, the particle sizes, and their relationship with sludge
      dewaterability (as determined by capillary suction time, CST). The sludge flocs
      were stratified through centrifugation- and ultrasound-based method into four
      fractions: (1) slime, (2) loosely bound extracellular polymeric substances (LB
      EPS), (3) tightly bound EPS (TB-EPS), and (4) pellet. The results showed that PN
      was mainly partitioned in the pellet (80.7%) and TB-EPS (9.6%) fractions, while
      PS distributed evenly in the four fractions. During hydrolysis and acidification,
      PN was transferred from the pellet and TB-EPS fractions to the slime fraction,
      but PS had no significant transfer trends. The mean particle sizes of the sludge
      flocs decreased with hydrolysis and acidification. The pH had a more significant
      influence on the dewaterability of sludge flocs than temperature. Sludge
      dewaterability during hydrolysis and acidification processes greatly deteriorated
      from 9.7 s at raw sludge to 340-450 s under alkaline conditions. However, it was
      just slightly increased under acidic conditions. Further investigation suggested
      that CST was affected by soluble PN, soluble PN/PS, and particle sizes of sludge
      flocs, but was affected slightly by total PN, PS, or PN/PS in the whole sludge
      flocs and other fractions (except slime).

PMID- 19402405
TI  - Degradation of o-chloronitrobenzene as the sole carbon and nitrogen sources by
      Pseudomonas putida OCNB-1.
AB  - A bacterial strain that utilized o-chloronitrobenzene (o-CNB) as the sole carbon,
      nitrogen and energy sources was isolated from an activated sludge collected from
      an industrial waste treatment plant. It was identified as Pseudomonas putida
      based on its morphology, physiological, and biochemical characteristics with an
      automatic biometrical system and the 16S rRNA sequence analysis. Microcosm study
      showed that the biodegradation of o-CNB was optimized at culture medium pH 8.0
      and 32 degrees C. At these conditions, the strain degraded 85% of o-CNB at a
      starting concentration of 1.1 mmol/L in 42 h. o-Chloroaniline was identified as
      the major metabolite with high performance liquid chromatography (HPLC) and gas
      chromatography-mass spectrometry (GC-MS). The study showed that o-CNB degradation
      by Pseudomonas putida OCNB-1 was initiated by aniline dioxyenase, nitrobenzene
      reductase and catechol-1,2-dioxygenase.

PMID- 19402406
TI  - Removal of haloacetic acids by nanofiltration.
AB  - Haloacetic acids, disinfection byproducts (DBPs) formed during drinking water
      chlorination process are carcinogens. The efficacy of nanofiltration (NF) was
      examined for the removal of five regulated haloacetic acids (HAA5): chloro-,
      dichloro-, and trichloro-acetic acid (CAA, DCAA, and TCAA); bromo-, and dibromo
      acetic acid (BAA, and DBAA) in synthetic water. NF with the dense negatively
      charged membrane (ES 10), is the most efficient in removing HAA5 than the loose
      negatively charged membrane (NTR 7410) and neutral surface membrane (NTR 729HF),
      due to the greater electrostatic repulsion (Donan exclusion) and sieve effect.
      Excellent HAA5 removal efficiency of 90%-100% could be obtained even at a low
      pressure of 1 x 10(5) Pa with ES 10. Changes in cross-flow velocity did not
      effect the performance of membranes with a small pore size such as ES 10 and NTR
      729HF. The increase in HAA5 concentration exhibited the adverse effect on the
      performance of three membranes by strengthening the concentration polarization,
      which was the driving force for the diffusion of HAA anions across the membrane.

PMID- 19402407
TI  - Exploitation of Fenton and Fenton-like reagents as alternative conditioners for
      alum sludge conditioning.
AB  - The use of Fenton's reagent (Fe2+/H2O2) and Fenton-like reagents containing
      transition metals of Cu(II), Zn(II), Co(II), and Mn(II) for an alum sludge
      conditioning to improve its dewaterability was investigated. The results obtained
      were compared with those obtained from conditioning the same alum sludge using
      cationic and anionic polymers. Experimental results show that Fenton's reagent
      was the best among the Fenton and Fenton-like reagents for the alum sludge
      conditioning. A considerable effectiveness of capillary suction time (CST)
      reduction efficiency of 47% can be achieved under test conditions of Fe2+/H2O2 =
      20/125 mg/g DS (dry solid) and pH 6.0. The observation of floc-like particles
      after Fenton's reagent conditioning of alum sludge suggested that the mechanism
      of Fenton's reagent conditioning was different from that of polymer conditioning.
      In spite of the lower efficiency in the CST reduction of Fenton's reagent in alum
      sludge conditioning compared to that of polymer conditioning, Fenton's reagent
      offers a more environmentally safe option. This study provided an example of
      proactive treatment engineering, which is aimed at seeking a safe alternative to
      the use of polymers in sludge conditioning towards achieving a more sustainable
      sludge management strategy.

PMID- 19402408
TI  - Competitive and cooperative adsorption of arsenate and citrate on goethite.
AB  - The fate of arsenic in natural environments is influenced by adsorption onto
      metal (hydr)oxides. The extent of arsenic adsorption is strongly affected by
      coexisting dissolved natural organic acids. Recently, some studies reported that
      there existed competitive adsorption between arsenate and citrate on goethite.
      Humic acid is known to interact strongly with arsenate by forming complexes in
      aqueous solution, hence it is necessary to undertake a comprehensive study of the
      adsorption of arsenate/citrate onto goethite in the presence of one another. The
      results showed that at the arsenate concentrations used in this study (0.006-0.27
      mmol/L), citrate decreased arsenate adsorption at acidic pH but no effect was
      observed at alkaline pH. In comparison, citrate adsorption was inhibited at
      acidic pH, but enhanced at alkaline pH by arsenate. This was probably due to the
      formation of complex between arsenate and citrate like the case of arsenate with
      humic acid. These results implied that the mechanism of the adsorption of
      arsenate and citrate onto goethite in the presence of one another involved not
      only competition for binding sites, but the cooperation between the two species
      at the water-goethite interface as well.

PMID- 19402409
TI  - Partitioning of water soluble organic carbon in three sediment size fractions:
      effect of the humic substances.
AB  - Water soluble organic carbon (WSOC) in sediments plays an important role in
      transference and transformation of aquatic pollutants. This article investigated
      the inherent mechanisms of how sediment grain size affect the partitioning
      coefficient (k) of WSOC. Influences of NaOH extracted humic substances were
      particularly focused on. Sediments were sampled from two cross-sections of the
      middle Yellow River and sieved into three size fractions (< 63 microm, 63-100
      microm, and 100-300 microm). The total concentration of WSOC in sediments
      (C(WSOC)) and k were estimated using multiple water-sediment ratio experiments.
      Results showed that C(WSOC) ranged from 0.012 to 0.022 mg/g, while k ranged from
      0.8 to 3.9 L/kg. Correlations between the spectrum characteristics of NaOH
      extracted humic substances and k were analyzed. Strong positive correlations are
      determined between k and the aromaticity indicators of NaOH extracted humic
      substances in different sediment size fractions. Comparing with finer fractions
      (< 63 pm), k is higher in larger size fractions (63-100 microm and 100-300
      microm) related to higher aromaticity degree of NaOH extracted humic substances
      mostly. While negative relationship between k and the area ratio of fourier
      transform infrared spectroscopy (FT-IR) at 3400 and 1430 cm(-1) implied that the
      lowest k was related to the highest concentration of acidic humic groups in
      particles < 63 microm. WSOC in finer fractions (< 63 microm) is likely to enter
      into pore water, which may further accelerate the transportation of aquatic
      contaminants from sediment to water.

PMID- 19402410
TI  - Disruption of biofilms from sewage pipes under physical and chemical
      conditioning.
AB  - Biofilms grown inside two sewage collecting pipes located in industrial and
      residential areas are studied. Bacterial biomass inside three layers of biofilms
      was evaluated. Biofilm cohesion under different mixing rate and ionic strength
      was also investigated. Effects of physical and chemical parameters in the
      biofilms were evaluated by monitoring turbidity, chemical and biochemical oxygen
      demands. Extracted organic matter from biofilms was partitioned to polar,
      aromatic and saturated fractions using activated silica column chromatography.
      Results revealed that bacterial biomass growth depending on biofilm thickness and
      stratification. The most loaded stratum in bacterial biomass was the sewage
      biofilm interface stratum that represented 51% of the total bacterial biomass.
      Stirring rate and ionic strength of mono- and bivalent salts showed a major
      influence in biofilm disruption. The stirring time enhanced the exchange dynamic
      and matter capture between biofilm fragments at the critical stirring rate 90
      r/min. Sodium chloride showed the dispersing effect on biofilms in suspension,
      and decreased the BOD5 (biochemical oxygen demand) beyond the physiological salt
      concentration.

PMID- 19402411
TI  - Evaluation of zeolites synthesized from fly ash as potential adsorbents for
      wastewater containing heavy metals.
AB  - The pure-form zeolites (A and X) were synthesized by applying a two-stage method
      during hydrothermal treatment of fly ash prepared initial Cu and Zn gel. The
      difference of adsorption capacity of both synthesized zeolites was assessed using
      Cu and Zn as target heavy metal ions. It was found that adsorption capacity of
      zeolite A showed much higher value than that of zeolite X. Thus, attention was
      focused on investigating the removal performance of heavy metal ions in aqueous
      solution on zeolite A, comparing with zeolite HS (hydroxyl-solidate) prepared
      from the residual fly ash (after synthesis of pure-form zeolite A from fly ash)
      and a commercial grade zeolite A. Batch method was used to study the influential
      parameters of the adsorption process. The equilibrium data were well fitted by
      the Langmuir model. The removal mechanism of metal ions followed adsorption and
      ion exchange processes. Attempts were also made to recover heavy metal ions and
      regenerate adsorbents.

PMID- 19402412
TI  - Environmental chamber study of the photochemical reaction of ethyl methyl sulfide
      and NO(x).
AB  - A series of experiments were conducted in a self-made smog chamber at (300 +/- 1)
      K and 1.01 x 10(5) Pa to simulate the photochemical reaction of ethyl methyl
      sulfide (EMS) and NO(x). The results showed that the higher the initial
      concentration of EMS, the more ozone was generated in the simulative reactions.
      It was found that the light intensity plays a very important role in the
      evaluation of ozone formation potential for EMS. The parameters of d(O3-NO) and
      IR (incremental reactivity) were used to quantify the potential of EMS on ozone
      formation. The obtained maximum IR values in this article for the five simulative
      reactions were 1.55 x 10(-2), 0.99 x 10(-2), 1.36 x 10(-2), 2.47 x 10(-2), and
      1.65 x 10(-2), respectively. A comparison between the results we obtained here
      and the results we obtained previously for di-tert-butyl peroxide and acetylene
      showed that the potential reactivity of EMS on ozone formation was at a
      relatively low level.

PMID- 19402414
TI  - Stimulation of gaseous phosphine production from Antarctic seabird guanos and
      ornithogenic soils.
AB  - Matrix-bound phosphine (MBP) is a general term used to indicate non-gaseous
      reduced phosphorus compounds that are transformed into phosphine gas upon
      reaction with bases or acids. Antarctic seabird guanos and ornithogenic soils
      were used as materials to compare the different digestion methods for
      transforming matrix-bound phosphine into phosphine gas. The results demonstrated
      that more phosphine gas in most of Antarctic environmental materials was formed
      of matrix-bound phosphine by caustic digestion than by acidic digestion. The
      comparative study on different digestion methods also revealed that the fraction
      of MBP converted to gaseous phosphine during the digestion depended on the
      temperature. The optimal digestion temperature was close to 70 degrees C and the
      optimal digestion time was about 20 min. Acidic conditions were more favorable
      for the release of matrix-bound phosphine compared to the neutral conditions. A
      proper water dilution can increase the production and emission of phosphine from
      the Antarctic penguin guanos.

PMID- 19402413
TI  - Distribution and sources of solvent extractable organic compounds in PM2.5 during
      2007 Chinese Spring Festival in Beijing.
AB  - The solvent extractable organic compounds (SEOC), including n-alkanes, polycylic
      aromatic hydrocarbons, fatty acids, and dicarboxylic acids in PM2.5 during the
      2007 Chinese Spring Festival in Beijing, were measured via gas chromatography
      mass spectrometry for determining the characteristics and sources of these
      organic pollutants. The concentrations of total n-alkanes, PAHs, and organic
      acids before Chinese Spring Festival Eve (1025.5, 95.9, and 543.3 ng/m3,
      respectively) were higher than those after (536.6, 58.9, and 331.8 ng/m3,
      respectively). n-Aalkanes and PAHs had much higher concentration in nighttime
      than those in daytime because of high relative humidity and low wind speed during
      the night. Combustion of coal and exhaust emission were major sources of n
      alkanes. It could be concluded by the characteristic ratios that the primary
      source of PAHs in fine particles was the combustion of coal, but the combustion
      of gasoline was in the next place. The ratios of C18:0/C16 indicated the
      contribution of vehicular emissions to the fatty acids. Dicarboxylic and aromatic
      acids were abundant in daytime than in nighttime because these acids were
      secondary organic acid and the photochemical degradation of aromatic hydrocarbons
      was the main source.

PMID- 19402415
TI  - Mass transfer in the absorption of SO2 and NO(x) using aqueous euchlorine
      scrubbing solution.
AB  - Attempts have been made to generate euchlorine gas by chlorate-chloride process
      and to utilize it further to clean up SO2 and NO(x) from the flue gas in a lab
      scale bubbling reactor. Preliminary experiments were carried out to determine the
      gas and liquid phase mass transfer coefficients and their correlation equations
      have been established. Simultaneous removal of SO2 and NO(x) from the simulated
      flue gas using aqueous euchlorine scrubbing solution has been investigated.
      Euchlorine oxidized NO into NO2 completely and the later subsequently absorbed
      into the scrubbing solution in the form of nitrate. SO2 removal efficiency around
      100% and NO(x) removal efficiency around 72% were achieved under optimal
      conditions. Mass balance has been confirmed by analyzing the sulfate, nitrate,
      euchlorine and chloride ion using ion chromatograph/auto-titrator and comparing
      it with their corresponding calculated values.

PMID- 19402417
TI  - Variation of grain Cd and Zn concentrations of 110 hybrid rice cultivars grown in
      a low-Cd paddy soil.
AB  - Enhanced Cd uptake and Zn depletion in rice grains and high potential for food Cd
      exposure by the high-yielding hybrid cultivars of China had been addressed. A
      field experiment was conducted in 2006 to determine the difference in grain Cd
      and Zn between cultivars. Total 110 cultivars including super rice and common
      hybrid rice cultivars were grown on a single paddy soil (Entic Haplaquept) with a
      neutral reaction and low total Cd content. Grain Cd and Zn concentrations were
      determined with graphite atomic adsorption spectrophotometer (GFAAS) and flame
      atomic adsorption spectrophotometer (AAS) respectively. Wide variation of Cd
      content in grain was found in a range of 0.004-0.057 mg/kg, while the Zn content
      in a range of 10.25-30.06 mg/kg among the cultivars. Higher Cd but lower Zn
      concentration in grains of super rice cultivars was observed compared to the
      common hybrid ones. A highly significant positive linear correlation of grain
      Cd/Zn with grain Cd was found for super rice and common hybrid cultivars,
      meanwhile much higher slope for these hybrid cultivars than the reported non
      hybrid cultivars was also observed. Using the limit value of the Chinese chemical
      guidelines for foods (MOHC and SSC, 2005), calculated potential risk of food Cd
      exposure with "Zn hungry" through diet intake was prominent with all the studied
      110 hybrid rice cultivars, possessing high potential health problems for rice
      production in South China using the super rice cultivars. Breeding of genotypes
      of rice cultivars with low grain Cd and low Cd/Zn ratio is needed for rice
      production in acidic red soils where Cd bioavailability is prevalently high.

PMID- 19402416
TI  - Size distribution and diffuse pollution impacts of PAHs in street dust in urban
      streams in the Yangtze River Delta.
AB  - Particles of dust washed off streets by stormwater are an important pathway of
      polyaromatic hydrocarbons (PAHs) into urban streams. This article presented a
      comprehensive assessment of the size distribution of PAHs in street dust
      particles, the potential risks of the particles in urban streams, and the sources
      and sinks of PAHs in the stream network. This assessment was based on
      measurements of 16 PAHs from the USEPA priority list in street dust particles and
      river sediments in Xincheng, China. The content of total PAHs ranged from 1629 to
      8986 microg/kg in street dust particles, where smaller particles have a higher
      concentrations. Approximately 55% of the total PAHs were associated with
      particles less than 250 microm which accounted for 40% of the total mass of
      street dust. The PAH quantities increased from 2.41 to 46.86 microg/m2 in the
      sequence of new residential, rising through main roads, old town residential,
      commercial and industrial areas. The sediments in stream reaches in town were
      found to be sinks for street dust particle PAHs. The research findings suggested
      that particle size, land use and the hydrological conditions in the stream
      network were the factors which most influenced the total loads of PAH in the
      receiving water bodies.

PMID- 19402418
TI  - Aging effect on the mobility and bioavailability of copper in soil.
AB  - Aging effect on the mobility and bioavailability of copper (Cu) was investigated
      using a spiked soil with different incubation periods from 3 to 56 d. Wheat was
      planted and earthworms were cultured separately in the incubated soils. The
      mobility of Cu in soil was evaluated by a chemical fractionation scheme and the
      toxicity and bioavailability were assessed by measuring the biomass and Cu
      concentration in tissues. Results showed that aging had a significant effect on
      Cu fraction distribution, of which Cu tended to incorporate from the exchangeable
      into more stable fractions such as the reducible and oxidisable fractions.
      However, aging had little effect on Cu bioavailability to wheat and earthworm.
      Comparing the soil being incubated for 3 d and 56 d, Cu concentration in wheat
      roots decreased from 14.5 to 12.8 mg/kg, and no significant changes in Cu
      concentration were observed in both wheat shoots and earthworms. The Cu
      concentration was around 2.0 and 50 mg/kg for wheat shoots and earthworms,
      respectively, irrespective of soil incubation time. The CaCl2-extractable Cu had
      a linear relationship with Cu concentration in wheat roots (R2 = 0.65, P < 0.05),
      but no linear relationship can be found for wheat shoots and earthworms.
      Biological control may be more crucial for Cu accumulation in organism than the
      changes in soil Cu fraction caused by aging.

PMID- 19402419
TI  - Effects of repeated applications of fungicide carbendazim on its persistence and
      microbial community in soil.
AB  - Carbendazim, a systemic benzimidazole fungicide, is applied repeatedly to control
      plant diseases including soilborne diseases, over a growing season. Studies were
      carried out under laboratory conditions to assess the effects of repeated
      carbendazim applications on its persistence and microbial community in soil. The
      results indicate that dissipation of carbendazim in soil was accelerated with its
      application frequency. The degradation rate constant of carbendazim was increased
      significantly from 0.074 d(-1) to 0.79 d(-1). The corresponding half-life was
      shorten markedly from 9.3 d to 0.9 d after four repeated applications. No
      significant inhibitory effect of carbendazim on soil microbial utilization of the
      carbon sources was observed after first treatment, but a slight increase in
      average well color development (AWCD) was shown after second, third, and fourth
      applications. It suggested that soil microorganisms become adapted to carbendazim
      after repeated application. Simpson and Shannon indexes of soil microbial
      community from carbendazim treated soil were also similar to those from the
      control soil, indicating that the richness and dominant character of soil
      microorganisms remain unchangeable after repeated application. However, after
      first, second, and third addition of carbendazim, McIntosh indexes on day 21 were
      significantly higher compared with the control, suggesting that balance of soil
      microorganisms was altered due to the enrichment of the specific carbendazim
      adapting strains in soil.

PMID- 19402421
TI  - Effects of heavy metal pollution of highway origin on soil nematode guilds in
      North Shenyang, China.
AB  - Soil samples were collected with distance at 5, 20, 40, 80, 160, and 320 m from
      the Shen-Ha (Shenyang-Harbin) Highway, Northeast China, to investigate the effect
      of heavy metals of highway origin on soil nematode guilds. The contents of soil
      Pb, Cu, Zn, and the nematode community structure were analyzed. The results
      showed that the contents of total and available Pb, Cu, Zn varied significantly
      with the different distances from the highway. Pb was the main pollutant in the
      soils in the vicinity of Shen-Ha Highway. The zone from 20 to 40 m away from the
      highway was the most polluted area. The highest abundance of soil nematodes was
      found at 5 m while the lowest at 20 m away from the highway. Thirty six genera of
      nematodes belonging to 23 families were identified. Nematode guilds having
      different responses to soil heavy metals were classified into four types. Soil
      nematode guilds may act as a prominent indicator to heavy metal pollution of
      highway origin.

PMID- 19402420
TI  - Effects of insoluble Zn, Cd, and EDTA on the growth, activities of antioxidant
      enzymes and uptake of Zn and Cd in Vetiveria zizanioides.
AB  - A root-bag experiment was conducted to study the effects of insoluble Zn, Cd, and
      ethylenediaminetetraacetic acid (EDTA) on the plant growth, activities of
      antioxidant enzymes, proline, glutathione (GSH), water-soluble proteins and
      malondialdehyde (MDA) of Vetiveria zizanioides. The V. zizanioides uptake
      capacity of Zn and Cd also determined. The results showed that plant growth of V.
      zizanioides was inhibited by Zn and Cd. The shoot dry weight (SDW) and root dry
      weight (RDW) decrease by 14.2%, 14.1%, 17.0% and 17.3%, 32.5%, 35.7%,
      respectively, compared to the control without EDTA addition. After adding EDTA,
      shoot and root dry weight decreased over 10% and 15%, respectively. The toxicity
      from insoluble Zn and Cd in soil on SDW and RDW of V. zizanioides was in order:
      Zn+Cd > Cd > Zn. The activities of superoxide dismutase (SOD), peroxidase (POD)
      and catalase (CAT), and contents of MDA and proline increased significantly,
      while the contents of GSH and water-soluble proteins decreased markedly with
      increasing Zn and Cd toxicity. With EDTA, shoot and root Zn concentrations
      increased in the Zn treatment by 7.3% and 37.4%, and Cd concentrations in the
      combined Zn and Cd treatment increased by 18.6% and 391.9% compared to the
      treatment without EDTA. However, Zn and Cd concentrations in shoot and roots
      decreased in the Cd treatment compared to the plants grown in absence of EDTA,
      with exception of root Cd concentration in the presence of EDTA.

PMID- 19402422
TI  - Changes of main secondary metabolites in leaves of Ginkgo biloba in response to
      ozone fumigation.
AB  - To investigate the effect of elevated O3 on the accumulation of main secondary
      metabolites in leaves of Ginkgo biloba L., four-year-old trees were exposed in
      open-top chambers with ambient air and the air with twice ambient O3
      concentration in Shenyang in 2006. Elevated O3 increased the concentrations of
      terpenes, but decreased the concentrations of phenolics in G. biloba leaves. The
      results showed that secondary compounds from G. biloba leaves responded to the
      elevated O3 exposure in a different way when compared to previous studies which
      showed elevated O3 increased the concentrations of phenolics but had no effect on
      the terpenes in leaves of other deciduous trees. Furthermore, reduced synthesis
      of phenolics may decrease the resistance of G. biloba to O3 and other
      environmental factors. On the other hand, the induced synthesis of terpenes may
      enhance the antioxidant abilities in G. biloba leaves at the end of O3
      fumigation.

PMID- 19402423
TI  - Enzyme extraction by ultrasound from sludge flocs.
AB  - Enzymes play essential roles in the biological processes of sludge treatment. In
      this article, the ultrasound method to extract enzymes from sludge flocs was
      presented. Results showed that using ultrasound method at 20 kHz could extract
      more types of enzymes than that at 40 kHz and ethylenediamine tetraacetic acid
      (EDTA) methods. The optimum parameters of ultrasound extraction at 20 kHz were
      duration of 10 min and intensity of 552 W/g TSS. Under the optimum condition,
      ultrasound could break the cells and extract both the extracellular and a small
      part of intercellular enzymes. Ultrasound intensity was apparently more
      susceptive to enzyme extraction than duration, suggesting that the control of
      intensity during ultrasound extraction was more important than that of duration.
      The Pearson correlation analysis between enzyme activities and cation contents
      revealed that the different types of enzymes had distinct cation binding
      characteristics.

PMID- 19402424
TI  - Isolation and characteristics of a novel biphenyl-degrading bacterial strain,
      Dyella ginsengisoli LA-4.
AB  - A novel biphenyl-degrading bacterial strain LA-4 was isolated from activated
      sludge. It was identified as Dyella ginsengisoli according to phylogenetic
      similarity of 16S rRNA gene sequence. This isolate could utilize biphenyl as sole
      source of carbon and energy, which degraded over 95 mg/L biphenyl within 36 h.
      The major metabolites formed from biphenyl, such as 2-hydroxy-6-oxo-6-phenylhexa
      2,4-dienoic acid (HOPDA) and benzoic acid, were identified by LC-MS. The crude
      cell extract of strain LA-4 exhibited the activity of 2,3-dihydroxybiphenyl 1,2
      dioxygenase (2,3-DHBD) and the kinetic parameters K(m) was 26.48 micromol/L and
      V(max) was 8.12 U/mg protein. A conserved region of the biphenyl dioxygenase gene
      bphA1 of strain LA-4 was amplified by PCR and confirmed by DNA sequencing.

PMID- 19402425
TI  - Expression of lignin peroxidase H2 from Phanerochaete chrysosporium by multi-copy
      recombinant Pichia strain.
AB  - The lipH2 gene, encoding the expression of lignin peroxidase, was cloned from
      Phanerochaete chrysosporium BKM-F-1767 and expressed in Pichia pastoris X-33, a
      yeast. The cDNA of LiPH2 was generated from total RNA extracted from P.
      chrysosporium by PCR with primers that do not contain a P. chrysosporium lignin
      peroxidase secretion signal. The gene was then successfully inserted into the
      expression vector pPICZalpha, and resulted in the recombinant vector pPICZalpha
      lipH2. The transformation was conducted in two ways. One was using the wild
      Pichia pastoris as the recipients, which results in the recombinant P. pastoris
      with single or low lipH2 gene copy. The second was using P. pastoris and single
      or low lipH2 gene copy as the recipients, which results in the recombinant P.
      pastoris with multi-copies of lipH2 genes. This study firstly expressed the gene
      lipH2 in P. pastoris and achieved the successful expression of the lipH2
      depending upon the generation of a recombinant strain that contained multiple
      copies. The lignin peroxidase activity reached a maximum of 15 U/L after 12 h
      induction.

PMID- 19402426
TI  - Monitoring microbial community structure and succession of an A/O SBR during
      start-up period using PCR-DGGE.
AB  - Polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE)
      protocol was employed for revealing microbial community structure and succession
      in a sequential anaerobic and aerobic reactor performing enhanced biological
      phosphorus removal (EBPR) during start-up period. High phosphorus removal was
      achieved after 15 d. On day 30, phosphorus removal efficiency reached to 83.2%
      and the start-up was finished. DGGE profiles of periodical sludge samples showed
      that dominant microbial species were 19 OTUs (operational taxonomy units).
      Unweighted pair-group method using arithmetic averages (UPGMA) clustering
      analysis revealed that rapid community succession correlated to low phosphorus
      removal rate and high phosphorus removal efficiency reflected on steady community
      structure. Sequencing results indicated that determined sequences (12 OTUs)
      belonged to Proteobacterium, Actinobacteria, Gemmatimonadales and unaffiliate
      group. Proteobacterium, Tetrasphaera elongate and Gemmatimonas aurantiaca may act
      important roles in phosphorus removal. With little amount as known glycogen
      accumulating organisms, Candidatus Competibacter phosphatis still at accumulating
      phase had limited effect on microbial community structure. When climax community
      was obtained, dominant microbes were 14 OTUs. Microbes in a large amount were
      uncultured bacterium Thauera sp., uncultured gamma-Proteobacterium and
      Tetrasphaera elongata.

PMID- 19402427
TI  - Bioaccumulation and depuration of chromium in the selected organs and whole body
      tissues of freshwater fish Cirrhinus mrigala individually and in binary solutions
      with nickel.
AB  - Contamination of aquatic ecosystems with heavy metals has been receiving
      increased worldwide attention due to their harmful effects on human health and
      other organisms in the environment. Most of the studies dealing with toxic
      effects of metals deal with single metal species, while the aquatic organisms are
      typically exposed to mixtures of metals. Hence, in order to provide data
      supporting the usefulness of freshwater fish as indicators of heavy metal
      pollution, it has been proposed in the present study to investigate the
      bioaccumulation and depuration of chromium in the selected organs of freshwater
      fingerlings Cirrhinus mrigala, individually and in binary solutions with nickel.
      The results show that the kidney is a target organ for chromium accumulation,
      which implies that it is also the "critical" organ for toxic symptoms. The
      results further show that accumulation of nickel in all the tissues of C. mrigala
      is higher than that of chromium. In addition, the metal accumulations of the
      binary mixtures of chromium and nickel are substantially higher than those of the
      individual metals, indicating synergistic interactions between the two metals.
      Theoretically the simplest explanation for an additive joint action of toxicants
      in a mixture is that they act in a qualitatively similar way. The observed data
      suggest that C. mrigala could be suitable monitoring organisms to study the
      bioavailability of water-bound metals in freshwater habitats.

PMID- 19402429
TI  - Differential degradation of crude oil (Bonny Light) by four Pseudomonas strains.
AB  - Four hydrocarbon degraders isolated from enriched oil- and asphalt-contaminated
      soils in Lagos, Nigeria, were tested for their petroleum degradation potentials.
      All the isolates were identified as species of Pseudomonas. Pseudomonas putida
      P11 demonstrated a strong ability to degrade kerosene, gasoline, diesel, engine
      oil and crude oil while P. aeruginosa BB3 exhibited fair degradative ability on
      crude oil, gasoline, engine oil, anthracene and pyrene but weak on kerosene,
      diesel and dibenzothiophene. Pseudomonas putida WL2 and P. aeruginosa MVL1 grew
      on crude oil and all its cuts tested with the latter possessing similar
      polycyclic aromatic potentials as P11. All the strains grew logarithmically with
      1-2 orders of magnitude and with generation time ranging significantly between
      3.07 and 8.55 d at 0.05 level of confidence. Strains WL2 and MVL1 utilized the
      oil substrate best with more than 70% in 6 d experimental period, whereas the
      same feat was achieved by P11 in 12 d period. BB3 on the other hand degraded only
      46% within 6 d. Interestingly, data obtained from gas chromatographic analysis of
      oil recovered from the culture fluids of MVL1 confirmed near-disappearance of
      major peaks (including aliphatics and aromatics) in the hydrocarbon mixture.

PMID- 19402428
TI  - Biodegradation of oil wastewater by free and immobilized Yarrowia lipolytica W29.
AB  - The ability of Yarrowia lipolytica W29 immobilized by calcium alginate to degrade
      oil and chemical oxygen demand (COD) was examined. The degradation rules of oil
      and COD by immobilized cells with the cell density of 6.65 x 106 CFU/mL degraded
      2000 mg/L oil and 2000 mg/L COD within 50 h at 30 degrees C (pH 7.0, 150 r/min),
      similarly to those of free cells, and the degradation efficiencies of oil and COD
      by immobilized cells were above 80%, respectively. The factors affecting oil and
      COD degradation by immobilized cells were investigated, the results showed that
      immobilized cells had high thermostability compared to that of free cells, and
      substrate concentration significantly affected degrading ability of immobilized
      cells. Storage stability and reusability tests revealed that the oil degradation
      ability of immobilized cells was stable after storing at 4 degrees C for 30 d and
      reuse for 12 times, respectively, the COD degradation rate of immobilized cells
      was also maintained 82% at the sixth cycle. These results suggested that
      immobilized Y. lipolytica might be applicable to a wastewater treatment system
      for the removal of oil and COD.

PMID- 19402430
TI  - Habitat influences on diversity of bacteria found on German cockroach in Beijing.
AB  - Cockroaches are worldwide indoor pests carrying microorganisms of medical
      importance. German cockroaches (Blattella germanica) were sampled in five
      habitats (hospital, restaurant, office home, and market) in Beijing, and the
      bacteria were isolated from their external surface and alimentary tract and
      identified using a Biolog identification system. Cockroach densities
      significantly differed among habitats (market > home > office > restaurant >
      hospital). However, no significant differences in bacterial abundance carried by
      individual German cockroaches (of either sex) were found among habitats. The
      bacterial abundance in the gut was significantly higher than that on the surface.
      There were no significant differences in bacterial species richness observed
      among habitats, sex, carrying position or their interaction. Cluster analysis
      showed that cockroach densities and bacterial abundance found in the market
      differed significantly from the other four habitats. The bacterial diversity was
      not significantly reduced in sensitive facilities such as hospital and
      restaurant, even though pesticide and bactericide were more frequently applied
      there. The implications of these findings were discussed in this article.

PMID- 19402431
TI  - Seasonal bioconcentration of heavy metals in Onchidium struma (Gastropoda:
      Pulmonata) from Chongming Island, the Yangtze Estuary, China.
AB  - The seasonal concentration changes of selected heavy metal Cd, Cr, Cu, Fe, Mn,
      Pb, and Zn in five tissues of marine gastropod Onchidium struma were studied in
      the Chongming Island, the Yangtze Estuary in April 2007, July 2006, September
      2006, and November 2006, respectively. The results demonstrated that the
      bioconcentration factor of Cu (biomass/water) in all selected tissues was about
      10(4) magnitudes, Fe and Cd were 10(3), Zn was 10(2), and Mn, Pb, and Cr were
      10(1). Hepatopancreas was proven to be the dominant storage tissue of Cr, Cu, Mn,
      and Zn, whereas Fe and Pb were mainly stored in muscle and digenetic gland, and
      Cd was stored in vitelline gland and albumen gland. Additionally, it was found
      that Cu, Fe, Mn, and Zn were concentrated significantly by O. struma (whole-body)
      in summer or autumn, and Cd, Cr, and Pb increased slightly in spring and winter.
      Furthermore, the bioconcentration of Cr was nearly 2-fold higher and Zn was 1.6
      fold higher in the water compared with the Water Quality Standard for Fisheries.
      With view of excessive amount of Pb, Cd, and Cu according to seafood standard,
      the consumption of O. struma might have the risk of health hazard.

PMID- 19402432
TI  - Effect of dye-metal complexation on photocatalytic decomposition of the dyes on
      TiO2 under visible irradiation.
AB  - The photocatalytic degradation of dyes (Acid Chrome Blue K (ACBK) and Alizarin
      Red (AR)) with strong complexation ability was investigated in the presence of
      metal ions under visible light irradiation. It was found that, at low dye-metal
      ratio, the photodegradation of ACBK was markedly inhibited by the addition of
      high oxidative potential Cu2+. However, at high dye-metal ratio, the presence of
      Cu2+ enhanced the photodegradation of ACBK. The negtive effect of Cu2+ on the
      photodegradation of AR was observed for all dye-metal ratios. The relative
      chemical inert Zn2+ tended to enhance the photodegradation of both anionic dyes.
      The mechanism underlying the different effect of Cu2+ was discussed from the
      different roles of surface-adsorbed and dye-coordinated Cu2+ in the
      photodegradation of dyes.

PMID- 19402433
TI  - Microwave photocatalytic degradation of Rhodamine B using TiO2 supported on
      activated carbon: mechanism implication.
AB  - The photocatalytic degradation of Rhodamine B (RhB) was carried out using TiO2
      supported on activated carbon (TiO2-AC) under microwave irradiation. Composite
      catalyst TiO2-AC was prepared and characterized using X-ray diffraction (XRD),
      transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET). In the
      process of microwave-enhanced photocatalysis (MPC), RhB (30 mg/L) was almost
      completely decoloured in 10 min, and the mineralization efficiency was 96.0% in
      20 min. The reaction rate constant of RhB in MPC using TiO2-AC by pseudo first
      order reaction kinetics was 4.16 times of that using Degussa P25. Additionally,
      according to gas chromatography/mass spectrometry (GC/MS) and liquid
      chromatography/mass spectrometry (LC/MS) identification, the major intermediates
      of RhB in MPC included two kinds of N-de-ethylation intermediates (N,N-diethyl-N'
      ethyl-rhodamine (DER)), oxalic acid, malonic acid, succinic acid, and phthalic
      acid, maleic acid, 3-nitrobenzoic acid, and so on. The degradation of RhB in MPC
      was mainly attributed to the destruction of the conjugated structure, and then
      the intermediates transformed to acid molecules which were mineralized to water
      and carbon dioxide.

PMID- 19402434
TI  - An ounce of prevention is worth a pound of cure.

PMID- 19402435
TI  - Working man's hero: a tribute to U.S. Representative Jim McGovern.

PMID- 19402437
TI  - Prevention: a key component to saving lives and money.
AB  - It's no mystery that one of the chief culprits to our current economic crisis is
      skyrocketing costs of providing health care, particularly to our nation's growing
      baby boom population. This makes the case all the more compelling to practice as
      much preventative care as possible to avoid a myriad of conditions that could
      lead to lengthy and costly hospital stays, and potentially even death.

PMID- 19402436
TI  - A call to action: supporting health care reform through sustaining the home care
      & hospice network.
AB  - On February 24, 2009, President Barack Obama addressed a joint session of the
      111th Congress and promised the American people that despite the Nation's current
      economic crisis, "We will rebuild, we will recover, and the United States of
      America will emerge stronger than before". As a central tenet of the 44th
      President's blueprint for restoring the country, he has committed to investing
      some $675 billion to move the nation toward health care coverage for all. In an
      effort to help make this a reality, the president has begun a series of public
      meetings to advance the discourse. I was privileged to be part of the initial
      Health Care Summit held at the White House on March 5, and look forward to
      participating in future discussions with policymakers and stakeholders.

PMID- 19402438
TI  - Prevention priorities for telehealth in health system reform.
AB  - Telehealth-supported innovations in offer the potential for yielding significant
      savings in the U.S. health care system--by some estimates, annual savings of 20
      percent or more (Deloitte, 2008). That would amount to $400 billion a year.

PMID- 19402439
TI  - The year of infection prevention.

PMID- 19402440
TI  - Cleaning and disinfection of patient care equipment used in the home setting.
AB  - Bringing medical equipment and devices into the home that has not been properly
      cleaned and disinfected constitutes an important reservoir for transmission of
      infection. By effectively combining the use of hand washing, barrier precautions,
      and meticulous cleaning and disinfection with an EPA-registered product, we
      should be able to continue to keep the home environment a safe place for our
      patients to receive care.

PMID- 19402441
TI  - Does your fall prevention program drive clinical decision making?
AB  - There is a significant amount of information available that outlines the negative
      impacts of falls in the aging population on both the individual's quality of life
      and the economics of health care delivery throughout the continuum.

PMID- 19402442
TI  - Automated fall detection: saving senior lives one fall at a time.
AB  - Many elderly have health issues which make falling asignificant likelihood. Falls
      may result from a variety of conditions such as mobility, difficulty from
      arthritis, vertigo from poor circulation, negative reactions to medication, etc.
      whatever the cause, more than one third of seniors will fall 1n a given year.
      This means that in the U.S. alone, 12 million seniors will fall this year.

PMID- 19402443
TI  - Early detection via telehealth: falls, infections, nutrition, dental.
AB  - The U.S. spends $2.3 trillion per year on health care, and economists warn that
      rising health care costs represent a serious threat to our long-term fiscal
      security. What is worse, according to the Congressional Budget Office, up to one
      third of that spending--more than $700 billion--does not improve Americans'
      health outcomes.

PMID- 19402444
TI  - Be a service warrior.

PMID- 19402445
TI  - Health care is not in a recession.

PMID- 19402446
TI  - Make the agency Web site a resource and watch the hits increase.

PMID- 19402447
TI  - Socrates, the surprising sales guru!

PMID- 19402448
TI  - The "STATE" of home care and hospice.
AB  - There is at least one home care and hospice industry association in each of our
      50 United States and Puerto Rico. These associations represent tens ofthousands
      of home care and hospice providers. They provide state and local leadership,
      professional and para-professional training, and other services designed to help
      home care and hospice providers care for our nation's sick, disabled, and
      elderly. These are their stories.

PMID- 19402449
TI  - Remembering Lillian Wald.

PMID- 19402450
TI  - Susceptibility of pike Esox lucius to a panel of Ranavirus isolates.
AB  - In order to study the pathogenicity of ranaviruses to a wild European freshwater
      fish species, pike Esox lucius fry were challenged with the following Ranavirus
      isolates: epizootic haematopoietic necrosis virus (EHNV), European sheatfish
      virus (ESV), European catfish virus (ECV), pike-perch iridovirus (PPIV), New
      Zealand eel virus (NZeelV) and frog virus 3 (FV3). The fry were infected using
      bath challenge at 12 and 22 degrees C. Significant mortalities were observed at
      12 degrees C for EHNV, ESV, PPIV and NZeelV. Background mortality was too high in
      the experiments performed at 22 degrees C for any conclusions about viral
      pathogenicity at this temperature to be drawn. Viruses could be re-isolated from
      samples from all challenged groups, and their presence in infected tissue was
      demonstrated using immunohistochemistry. The findings suggest that pike fry are
      susceptible to EHNV, ESV, PPIV and NZeelV and can be a vector for ECV and FV3.
      Statistical analysis of the factors associated with positive virus re-isolation
      showed that the number of fish in the sample influenced the outcome of virus re
      isolation. Moreover, the likelihood of positive virus re-isolation significantly
      differed among the 6 viral isolates. The temperature from where the sample was
      taken and the number of days after infection were not associated with the
      probability of a positive virus re-isolation.

PMID- 19402451
TI  - Viral gametocytic hypertrophy of the Pacific oyster Crassostrea gigas in Ireland.
AB  - Viral gametocytic hypertrophy (VGH) was detected during an investigation of
      mortalities in Pacific oysters Crassostrea gigas from 2 separate Irish production
      sites. The basophilic inclusions were observed in the gonad tissue of oysters
      sampled in August and October 2007. The oysters involved did not show any
      macroscopic disease signs. Transmission electron microscopy demonstrated the
      presence of viral particles in these intranuclear inclusions. The particles were
      small, non-enveloped, icosahedral and approximately 50 nm in diameter, and thus
      had characteristics similar to the Papillomaviridae and Polyomaviridae families.
      No host defence reaction was observed. The viral particles described here appear
      to be similar to those described in C. virginica from the USA and Canada and to
      those described in C. gigas from Korea and France.

PMID- 19402452
TI  - Effects of the pathogenic water mold Saprolegnia ferax on survival of amphibian
      larvae.
AB  - Infectious diseases are a significant threat to worldwide biodiversity. Amphibian
      declines, a significant part of current biodiversity losses, are in many cases
      associated with infectious disease. Water molds are one group of pathogens
      affecting amphibians on a worldwide basis. Although water molds have been studied
      extensively for their effects on host embryos, little information is available
      about how they affect post-embryonic amphibians. We tested the effects of one
      species of water mold, Saprolegnia ferax, in a comparative study of larvae of 4
      amphibian species: Pseudacris regilla (Pacific treefrog), Rana cascadae (Cascades
      frog), Ambystoma macrodactylum (long-toed salamander), and R. aurora (red-legged
      frog). S. ferax can kill amphibians at the embryonic and juvenile life history
      stages, depending on the amphibian species. In the present study, a 1 wk exposure
      to S. ferax killed P. regilla larvae and a 2 wk exposure killed R. aurora larvae.
      Larvae of the other host species were unaffected after 1 wk of exposure to S.
      ferax. Our results suggest that S. ferax can kill amphibian larvae and further
      suggest that evaluation of how pathogens affect amphibians at the population
      level requires investigation at various life stages.

PMID- 19402453
TI  - Spatial variability in distribution and prevalence of Caribbean scleractinian
      coral and octocoral diseases. I. Community-level analysis.
AB  - Geographic assessments of coral diseases are needed to understand their local and
      geographic spatial-temporal variability. Coral and octocoral diseases and their
      prevalence were assessed along 4 permanent 10 x 2 m band-transects in each of 3
      depth habitats (<4, 5-12 and >15 m) in each of 2 reefs in each of 6 countries
      across the wider Caribbean during the summer and fall of 2005. A permutational
      multivariate analysis of variance was used to test variability of major diseases
      and community level disease prevalence in corals and octocorals among habitats,
      reefs and countries. The most common and damaging diseases reported for the
      region were found in most reefs surveyed, but prevalence at the community level
      was generally low (ca. 2%) increasing from northern to southern latitudes. A
      significant interaction between sites (nested within country) and depth habitats
      was found (F = 2.1, df = 12, p = 0.02), with higher prevalence of coral diseases
      in deep habitats of Culebrita, Puerto Rico (14.8 +/- SE 6.5%) and in shallow
      habitats of Roldan, Panama (10.2 +/- SE 3.5%). The relative importance of each
      particular disease was dependent on site and habitat (depth intervals) (F = 1.7,
      df = 12, p = 0.001), with black band disease more prevalent in shallow habitats
      of Rita's, Bermuda (1.7 +/- SE 0.4%) and yellow band disease (YBD) more prevalent
      in deeper habitats of Chub Cut, Bermuda (3.7 +/- SE 0.5%). There was a
      significant interaction of total octocoral diseases with country and habitat (F =
      2.8, df = 10, p = 0.04) with higher prevalence in deeper habitats of Curacao
      (25.9 +/- SE 4.2%). Our results indicate that patterns of prevalence of coral and
      octocoral diseases were not consistent across the different spatial scales,
      showing differences produced by particular diseases and community composition
      present. There were no widespread epizootics, but local white plague-II and YBD
      epizootics were observed in Puerto Rico and other localities.

PMID- 19402454
TI  - Spatial variability in distribution and prevalence of Caribbean scleractinian
      coral and octocoral diseases. II. Genera-level analysis.
AB  - Geographic assessments of coral/octocoral diseases affecting major reef-building
      genera and abundant reef species are important to understand their local and
      geographic spatial-temporal variability and their impact. The status and spatial
      variability of major Caribbean coral/octocoral diseases affecting important reef
      building coral (Montastraea, Diploria, Siderastrea, Stephanocoenia, Porites, and
      Agaricia) and common, widespread octocoral genera (Gorgonia and
      Pseudopterogorgia) was assessed along 4 permanent 10 x 2 m band-transects in each
      of 3 depth habitats (<4, 5-12 and >15 m) on 2 reefs in 6 countries across the
      wider Caribbean during the summer and fall of 2005. A permutational multivariate
      analysis of variance was used to test the spatial variability (countries, reef
      sites and depth habitats) in prevalence of major diseases in these genera. We
      found a significant interaction of disease prevalence in the different coral and
      octocoral genera between reef sites and habitats (depth intervals). Montastraea
      was primarily affected by both white plague (WP-II) and yellow band disease in
      deep (16.9 +/- SE 16% and 16.9 +/- SE 2.3%) and intermediate (8.1 +/- SE 1.6% and
      15.5 +/- SE 2.3%) depth habitats of Culebrita (Puerto Rico) and Chub Cut
      (Bermuda), respectively. Prevalence of multiple diseases simultaneously and other
      compromised-health problems affecting Montastraea colonies varied between 0.2 to
      2% and 0.2 to 1.8%, respectively. Agaricia and Diploria were mostly affected by
      WP-II (0.5 to 16%), black band disease (0.4 to 5%) and Caribbean ciliate
      infections (0.2 to 12%). Siderastrea and Stephanocoenia were mainly affected by
      dark spots disease in Curacao, with higher prevalence in intermediate (40.5 +/-
      SE 6.2%) and deep (26.6 +/- SE 4.2%) habitats. Aspergillosis and other
      compromised-health conditions affected Gorgonia ventalina (0.2 to 8%) and other
      common and widespread octocoral genera (1 to 14%), respectively.

PMID- 19402455
TI  - Effect of viral hemorrhagic septicemia virus on Pacific herring in Prince William
      Sound, Alaska, from 1989 to 2005.
AB  - We critically review the role of viral hemorrhagic septicemia virus (VHSV) in the
      1992-1993 collapse of the Prince William Sound (PWS) herring fishery. VHSV was
      detected in samples of moribund Pacific herring from PWS in spring 1993 when
      about 63% of the expected fish failed to appear. A low prevalence and severity of
      VHSV were observed in adult pre-spawning PWS herring in most of the years from
      1994 to 2002. The North American strain of VHSV became established about 500 yr
      ago in many northeast Pacific marine fish species, including herring. In Alaska,
      the typical annual prevalence of VHSV in pre-spawning herring ranges from 0 to
      17%. New threshold analysis of a 9 yr study indicates that only about half of the
      virus-infected adult fish in PWS were clinically affected; ulcers formerly
      attributed to VHS have been overestimated by a factor of about 3. We conclude
      that VHSV was not a primary causative factor in the PWS herring population
      collapse or in its failure to recover. Because older age classes of herring were
      not disproportionately missing in 1993, the protozoan Ichthyophonus hoferi was
      also not a likely cause of losses. The 'Exxon Valdez' oil spill occurred in PWS,
      Alaska, U.S.A., in 1989. Evidence for interaction of oil and VHSV expression is
      also evaluated. A study exposing herring to varying concentrations of weathered
      crude oil showed increasing prevalences of VHSV correlated with oil
      concentration; however, repeated experiments with juvenile and adult fish failed
      to corroborate these results or link oil to VHSV infection in herring.

PMID- 19402456
TI  - Inter-relationships of haplosporidians deduced from ultrastructural studies.
AB  - We reviewed papers reporting haplosporidian ultrastructure to compare inter
      relationships based on ultrastructure with those based on molecular data, to
      identify features that may be important in haplosporidian taxonomy, and to
      consider parasite taxonomy in relation to host taxonomy. There were links between
      the following: (1) the plasmodia of an abalone parasite, Haplosporidium nelsoni
      and Urosporidium crescens in the release of haplosporosomes; (2) H. costale and
      H. armoricanum in haplosporosome shape and presence and shape of Golgi in spores;
      (3) basal asporous crustacean haplosporidians which form haplosporosomes from
      formative bodies (FBs) in vegetative stages--H. nelsoni, which forms
      haplosporosomes from FBs in plasmodial cytoplasm, and H. louisiana, Minchinia
      spp. and Bonamia perspora, which form haplosporosomes from FBs in spores; (4)
      crustacean haplosporidians, Bonamia spp. and M. occulta in the predominance of
      uni- and binucleate stages; and (5) lipid-like vesicles in sporoplasms of H.
      costale, H. armoricanum, H. lusitanicum, H. pickfordi, H. montforti, and B.
      perspora. In general, these relationships reflect phylogenies based on molecular
      studies. As well as spore form and ornamentation, haplosporogenesis in spores
      appears to be taxonomically important. Parasite and host taxonomy were linked in
      the infection of lower invertebrates by Urosporidium spp., the infection of
      oysters by Bonamia spp., and of molluscs by Minchinia spp. Haplosporidium spp.
      are patently an artificial, paraphyletic group probably comprising many taxa.
      Consequently, the taxonomy of haplosporidians needs a thorough revision.

PMID- 19402457
TI  - Using itraconazole to clear Batrachochytrium dendrobatidis infection, and
      subsequent depigmentation of Alytes muletensis tadpoles.
AB  - Batrachochytrium dendrobatidis (Bd) is a global threat to amphibian biodiversity.
      Current calls for conservation through captive breeding require that efficient
      and reliable antifungal treatments be developed for target species. Here we
      confirm that the antifungal itraconazole is an effective treatment for infection
      in larval Alytes muletensis. Exceptionally low doses applied as few as 7 times
      were effective at clearing infection from tadpoles for up to 28 d after
      treatment. However, we cannot recommend itraconazole as a treatment for this
      species as depigmentation of tadpoles was observed. Further research is required
      to determine the putative hepatotoxicity of this treatment.

PMID- 19402458
TI  - Cohort changes in the retirement resources of older women.
AB  - Dramatic changes in life expectancy, women's roles in the labor market, the
      structure of the workforce, and pension systems have occurred in recent decades,
      all influencing the wellbeing of future retirees. This article uses different
      sources of U.S. data to focus on the retirement resources of women aged 55-64. By
      comparing the resources for this age group in 2004 to their counterparts in 1994
      and 1984, this analysis provides some indication of changes in the retirement
      preparedness of three different cohorts of women. Our findings indicate that
      notable changes have occurred with women's pathways into retirement that are due
      to increased education and lifetime work experience. As a consequence, there are
      marked differences in potential retirement outcomes. We find that women aged 55
      64 today are better prepared in several respects than their counterparts of the
      same age 10 or 20 years ago.

PMID- 19402459
TI  - Simplifying the Supplemental Security Income program: options for eliminating the
      counting of in-kind support and maintenance.

PMID- 19402460
TI  - A legislative history of the Social Security Protection Act of 2004.
AB  - Passage of the original Social Security Act in 1935, Public Law (P.L.) 74-271,
      represented one of the watershed achievements of social welfare reform in
      American history. For the first time, workers were guaranteed a basic floor of
      protection against the hardships of poverty. In the ensuing decades, more than
      100 million beneficiaries have realized the value of this protection through the
      receipt of monthly Social Security payments. As this guarantee has endured and
      progressed, the policies and administration of such a vast and complex program
      have required ongoing modifications-more than 150 such revisions over the past 73
      years. To some extent, these amendments can be seen as an ongoing refinement
      process, with the Social Security Protection Act of 2004 (SSPA) being another
      incremental step in the development of a social insurance program that best meets
      the evolving needs of American society. This article discusses the legislative
      history of the SSPA in detail. It includes summaries of the provisions and a
      chronology of the modification of these proposals as they passed through the
      House and Senate, and ultimately to the president's desk.

PMID- 19402462
TI  - Pediatric ophthalmic hemangiomas: a review and surgical case study.

PMID- 19402461
TI  - Doing more with less--deja vu?

PMID- 19402463
TI  - Primary congenital glaucoma: making strides in genetic testing, early detection
      and treatment.

PMID- 19402464
TI  - Telephone techniques and triage in the ophthalmology office.

PMID- 19402465
TI  - Heart SOS.

PMID- 19402466
TI  - Decision-making and dementia.

PMID- 19402467
TI  - A living legend. Interview by Kenya Haney.

PMID- 19402468
TI  - Finding guidance through friendship.

PMID- 19402469
TI  - Fashioning the right impression.

PMID- 19402470
TI  - Projecting your professionalism.
AB  - Nursing is identified as a profession because it requires both extensive
      education in science and specialized training. But simply working in an
      identified profession does not automatically make one a professional.
      Professionalism involves much more than degrees and credentials. It includes a
      certain work ethic, attitude, code of conduct, appearance, communication style,
      among other matters. So what does it take to be a true professional and what does
      professional behavior, demeanor and appearance look like?

PMID- 19402471
TI  - The growth and development of professional nurses.
AB  - As individuals enter nursing programs, the process of socialization in the
      professional role begins. Novice nursing students learn the definition of
      professionalism, standards of practice and the code of ethics. For many, the
      concept of professionalism is quite new, including one's appearance, behaviors
      and communication.

PMID- 19402472
TI  - Your professional presence: advice on dress and appearance.

PMID- 19402473
TI  - Are you listening? Improving our image by sharpening our communication skills.

PMID- 19402474
TI  - Bringing your own flavor to nursing.

PMID- 19402475
TI  - [Quantifying direct N2O emissions from paddy fields during rice growing season in
      China: model establishment].
AB  - Various water management regimes, such as continuous flooding (F), flooding
      midseason drainage-reflooding (F-D-F), and flooding-midseason drainage-reflooding
      moist intermittent irrigation but without water logging (F-D-F-M), are currently
      practiced in paddy rice production in China. These water regimes have incurred a
      sensitive change in direct N2O emission from rice paddy fields. In order to
      establish statistical models quantifying the country-specific emission factor and
      background emission of N2O in paddy fields during the rice growing season, we
      compiled and statistically analyzed field data on 71 N2O measurements from 17
      field studies that were published in peer-reviewed Chinese and English journals.
      For each field study, we documented the seasonal N2O emission, the type and
      amount of organic amendment and fertilizer nitrogen application, the water
      management regime, the drainage duration, the field location and cropping season.
      Seasonal total N2O was, on average, equivalent to 0.02% of the nitrogen applied
      in the continuous flooding rice paddies. Under the water regime of F-D-F or the F
      D-F-M, seasonal N2O emissions increased with N fertilizer applied in rice
      paddies. Applying an Ordinary Least Square (OLS) linear regression model resulted
      in an emission factor of 0.42% for N2O, and in unpronounced background N2 O
      emission under the water regime of F-D-F. Under the F-D-F-M water regime, N2O
      emission factor and N2O-N background emission were estimated to be 0.73% and 0.79
      kg x hm(-2) during the paddy rice growing season, respectively. After considering
      three different water regimes in rice paddies in China, the emission factor of N
      for N2O and N2O-N background emission averaged 0.54% and 0.43 kg x hm(-2). The
      results of this study suggest that paddy rice relative to upland crop production
      could have contributed to mitigating N2O emissions from agriculture in China. The
      emission factor of N for N2O and its background emissions can be directly adopted
      to develop national inventory of N2O emissions from paddy fields during the rice
      growing season in China.

PMID- 19402476
TI  - [Process study on hysteresis of vegetation cover influencing sand-dust events].
AB  - Data analysis from satellite and weather stations during 1982-2000 shows
      nonlinear relationship between vegetation cover and sand-dust events is present
      in most part of China. Vegetation cover ratio in summer can impact significantly
      on the frequency of sand-dust storms from winter to spring in the source regions
      of sand-dust events. It is not quite clear about the hysteresis that vegetation
      cover in summer influence sand-dust events during winter and spring. A quasi
      geostrophic barotropic model is used under the condition of 3 magnitude of
      frictional coefficient to investigate the cause of the hysteresis. Wind velocity
      shows a greatest decline at 90% during 72 h as initial wind velocity is 10 m/s
      for magnitude of frictional coefficient between atmosphere and water surface,
      greatest decline at 100% during 18 h for magnitude of frictional coefficient
      between atmosphere and bare soil and a 100% reduction of wind speed during 1 h
      for magnitude of frictional coefficient between atmosphere and vegetation cover.
      Observation and simulation prove that residual root and stem from
      summervegetation are one of factors to influence sand-dust events happened during
      winter and spring. Air inhibition from residual root and stem is a most important
      reason for hysteresis that vegetation cover influence sand-dust events.

PMID- 19402477
TI  - [Spatial-temporal variations of extractable organic matter in atmospheric PM10
      and PM2.5 in Beijing].
AB  - PM10 and PM2.5 samples were collected in parallel in different function zones of
      Beijing during four seasons of 2005. The pollution level, distribution
      characteristics of the extractable organic matter (EOM) and relationship between
      EOM (PM10) and EOM (PM2.5) were illustrated. The results show that: the annual
      mean concentrations of organic compound in PM10 and PM2.5 are 41.39 microg/m3 and
      34.84 microg/m3, being 1.44 times and 1.26 times higher than Ming Tombs site. The
      concentrations of EOM in winter are 67.04 microg/m3 (PM10) and 64.64 microg/m3
      (PM2.5), which are 1.15 and 1.82 times, 2.06 and 2.26 times, 4.53 and 6.26 times
      higher than that in spring, autumn, summer, respectively. Ratios of EOM in PM2.5
      to that in PM10 in different seasons exceed 0.60. In different function zones the
      concentrations of EOM present industrial and commercial zones > living, traffic
      and contrast zones. The influence of EOM (PM2.5) on EOM (PM10) in different
      districts are various. The order of annual concentrations of organic compositions
      is non-hydrocarbons > asphaltenes > aromatics > saturated hydrocarbon. The
      seasonal emissions of pollution sources play an important role in seasonality of
      compositions of EOM.

PMID- 19402479
TI  - [POC content in size-fractioned TSS and transportation character in the Yellow
      River].
AB  - Relationship between grain size of total suspended solids (TSS) and particulate
      organic carbon (POC) content is the base of studying POC transportation and flux
      in river. Based on sedimentation classification, POC in size-fractioned TSS of
      The Yellow River was studied by multiple linear regression. The results indicate
      that: with the median diameter increasing, POC is decreased in a logarithm
      tendency, the maximum is 0.56% lower than the other rivers; POC is different in
      the same size-fractioned TSS between characteristic sample stations: the estuary
      > Huayuankou > Lanshou > Tongguan > Lijin, for example POC is 0.661%, 0.627%,
      0.550%, 0.505%, 0.493% in TSS of which the grain size is < 8 microm; the
      proportion of POC in size-fractioned TSS has little distinction, POC is decreased
      remarkably with the increasing of the grain size of TSS, and more than 80% of POC
      is concentrated in the particles < 16 microm while over 95% of POC is
      concentrated in particles of size < 32 microm. So the transportation of POC is
      consistent, the main control of transportation of POC is attributed to the grain
      size of TSS.

PMID- 19402478
TI  - [Unregulated emissions from the gasoline vehicle].
AB  - Based on the emission test cycle of China National Regulation Stage III, the
      aldehyde and alkone emissions and VOCs emissions of three typical gasoline cars
      were studied with HPLC and TD-GC/MS and the exhausted particulates number and
      mass concentration were researched using ELPI. The results indicate that the
      unregulated emissions of different cars is diverse changed, the brake specific
      emission of the carbonyls in three cars are 36.44, 16.71 and 10.43 mg/km
      respectively and TVOC are 155.39, 103.75 and 42.29 mg/km respectively.
      Formaldehyde, acetaldehyde, acrolein, acetone and cyclohexanone are the main
      compounds in gasoline cars exhaust, which accounted for 77.9%-89.7% of total
      carbonyl compounds. Aromatic hydrocarbons and alkane are the main part of VOCs,
      the detected number of which is occupied 31.6%-39.2% and 23.1%-27.9% of VOCs.
      Toluene, xylene and benzene have high concentration, which are occupied 16.68%,
      16.87% and 5.23% of TVOC in average. Ultra-fine particles (< 100 nm) dominate the
      particulates emission. Exhausted particulate number of high speeds is higher than
      that of slow and medium speeds.

PMID- 19402480
TI  - [Characteristics of the diffuse attenuation coefficient and its impact on aquatic
      ecology environment].
AB  - According to the optical property data measured in Taihu Lake at October and
      November 2006, the characteristics of the diffuse attenuation coeffcient (Kd),
      the contribution of each factor effecting on Kd and the effect of Kd on the
      aquatic ecology environment were analyzed. The results indicate that, the diffuse
      attenuation coefficient Kd of Taihu Lake has two main trends in the whole visible
      wavelength range (400-700 nm). The first type is that, Kd decreases with the
      wavelengths by exponential style in the range of less than 571 nm wavelengths,
      and the second type is that, Kd is in the form of fluctuations in the range of
      larger than 571 nm wavelengths. In the range of 400-700 nm wavelength, the
      absorption coefficient of pigment particles is the first contributors of diffuse
      attenuation coefficient. Non-pigment particles absorption and scattering
      coefficients is the second contributor, and the rate of contribution of yellow
      substance is the smallest. The Kd of Taihu Lake determines the light factor of
      the Taihu water ecosystem. The "water window" shaped by the Kd provides the light
      base for different kinds of ecosystem and the appearance of Microcystic
      aentginosa which is the preponderant algae in the "algal blooms" phenomenon.

PMID- 19402481
TI  - [Acidity characteristics and element flux of rainwater in the hilly area of south
      Anhui, China].
AB  - The current study takes the hilly south Anhui province as the study area, which
      is located in the subtropical China and far from urban and industrial activities.
      The rainwater samples were collected from April to November in 2007 and were
      determined for pH, major cations and anions, to estimate acidity characteristics
      and the sum of hydrogen ion and other cation and anion input during the studied
      period. The results showed that the frequency of acid rain was over 92%, with an
      average pH of 4.61. The average concentrations of SO4(2-) and Ca2+ were 39.69
      microeq/L and 68.82 microeq/L respectively, which were the most abundant cation
      and anion among the determined elements. The atmospheric pollution was
      characterized as SO2 and NOx with an average of SO4(2-)/NO3(-) 1.23 in the
      rainwater. The variation of the major chemical component in the rainwater with
      time implied that the atmospheric NOx mainly originated from the local
      agricultural activities, while SO2 was mainly affected by non-local source and
      the base cation was mainly affected by dust transportation during spring season.
      The total input of base cation and H+ was 1,289 eq/hm2 and 360 eq/hm2
      respectively, while that of SO4(2-) and NO3(-) was 926 eq/hm2 from April to
      November in 2007. The input of acid deposition may have a detrimental effect on
      the local ecosystem.

PMID- 19402483
TI  - [Transport and sources of runoff pollution from urban area with combined sewer
      system].
AB  - Sampling and monitoring of runoff and sewage water in Wuhan urban area with
      combined sewer system were carried out during the period from 2003 to 2006, to
      study the transport and sources of runoff pollution at the catchment scale
      coupled with environmental geochemistry method. The results showed a change in
      quality between the runoff entering the sewer network and the combined storm
      water flow at the sewer's outlet. A significant increase was observed in the
      concentrations of total suspended solids (TSS), volatile suspended solids (VSS),
      COD, TN, and TP, and in the proportion of COD linked to particles. During the
      runoff production and transport, the concentrations of TSS and COD increased from
      18.7 mg/L and 37.0 mg/L in roof runoff, to 225.3 mg/L and 176.5 mg/L in street
      runoff, and to 449.7 mg/L and 359.9 mg/L in combined storm water flow,
      respectively. The proportion of COD linked to particles was increased by 18%. In
      addition, the total phosphorus (P) and iron (Fe) contents in urban ground dust,
      storm drain sediment, sewage sewer sediment and combined sewer sediment were
      measured to identify the potential sources of suspended solids in the combined
      flow. The urban ground dust andstorm drain sediment wererich in Fe, whereas the
      sewage sewer sediment was rich in P. The P/Fe ratios in these groups were
      significantly distinct and able to differentiate them. A calculation of the two
      storm events based on the P/Fe rations showed that 56% +/- 26% of suspended
      solids in combined flow came from urban ground and storm drain. The rest wer e
      originated from the sewage sewer sediments which deposited in combined sewer on
      the dry weather days and were eroded on the wet weather days. The combined sewer
      network not only acts as a transport system, but also constitutes a
      physicochemical reactor that degrades the quality of urban water. Reducing the in
      sewer pollution stocks would effectively control urban runoff pollution.

PMID- 19402482
TI  - [Analysis on chemical compositions of rainwater in summer, Lijiang City, China].
AB  - Rainwater samples were colleted from Lijiang City, China, in 23 May-2 July, 2006.
      Rainwater chemical compositions and sources were studied, using HYSPLIT model,
      ions tracer techniques, correlation and trend analysis. Total ionic concentration
      was dominated by SO4(2-) and Ca2+, which account for 65.5% and 15.6%
      respectively. Sort order of ions concentration is SO4(2-) > Ca2+ > Cl(-) > NO3(-)
      > Na+ > K+ > Mg2+. Total anions concentration is higher than total cations
      concentration in 13 rainwater events. The ratio of SO4(2-) to NO3(-) varies from
      7.2 to 37.1 and average value is 15.7, it reflected SO4(2-) made great
      contribution to rainwater acidity in Lijiang City. The correlation among ions is
      significant due to the atmospheric chemical process and similar ionic sources,
      and correlation coefficient between SO4(2-) and NO3(-) is 0.74. And what's more,
      the negative correlation of ionic concentration, precipitation and the average
      wind speed is also outstanding. The source of NO3(-), SO4(2-), K+ and Ca2+ is
      mainly land dust, and the non-marine source percent of NO3(-), SO4(2-), K+, Ca2+,
      Mg2+ and Cl(-) is 100%, 98.8%, 96%, 99.3%, 46.7% and 50.3%, respectively. The
      main reason of atmospheric environmental variation in Lijing City is pollution
      caused by economic actions. The pollutants from surrounding industrial parks
      input into Lijiang City by local circulation, and from industrial regions of
      Southern Asia, Southeastern Asia and Southeastern China input into Lijiang City
      by monsoonal circulation.

PMID- 19402484
TI  - [Effects of near-surface soil water conditions on agricultural non-point source
      pollutant transport].
AB  - Agricultural non-point source pollution is one of severe problems for water
      environment of agricultural area in China. The effects of near-surface soil water
      conditions on agricultural non-point source pollutant (AGNSP) transport during
      soil erosion processes, especially antecedent soil moisture was saturated, was
      developed by using artificial simulation rainfall experiment. The results showed
      that antecedent soil water content had great impact on AGNSP transport during
      soil erosive processes. Under the same soil texture, the AGNSP concentration and
      loading with runoff and sediment when the antecedent soil water content was
      saturated were greater than that of soil moisture un-saturated condition, and
      they would be increased as antecedent soil moisture increased. The approach of
      soil nitrogen loss was rainfall runoff; nitrogen loss with runoff was about 90.4%
      to 99.8% of total loss. The approaches of soil phosphorus were runoff and soil
      loss (sediment), the loss with runoff was about 2.67% to 23.5%, and the loss with
      sediment was about 76.5% to 97.3%. Soil texture had great influence on soil
      phosphorus loss; the concentration and loading of dissolved phosphorus (DP) with
      sediment from Yangling Loutu were greater than that of Ansai Loess. Some
      pertinence suggestions were given to control agricultural non-point source
      pollution, such as the best management practices.

PMID- 19402485
TI  - [Priority analysis for controlling endocrine disrupting chemicals in municipal
      wastewater treatment plants of China].
AB  - Ecological risk quotients and estradiol equivalent concentrations of 32 endocrine
      disrupting chemicals (EDCs) in 4 categories were calculated and analyzed using
      reported concentrations in secondary effluents from municipal wastewater
      treatment plants in China, considering both extreme scenario for maximum
      concentration and moderate scenario for median concentration. These EDCs include
      industrial chemicals, pesticides, natural estrogens, and pharmaceuticals. In
      extreme scenario, 12 chemicals of ecological risk and 9 chemicals of
      estrogenicity were identified. While in moderate scenario, 6 chemicals of
      ecological risk and 5 chemicals of estrogenicity were identified. After further
      scoring and ranking, 4 priority EDCs have been suggested for control in municipal
      wastewater treatment plants in China, including 17a-ethynylestradiol, estrone,
      nonylphenol, and bisphenol A.

PMID- 19402486
TI  - [Ecological risk assessment of the DAT-IAT process for municipal wastewater
      treatment].
AB  - By using the regular water-quality indices and the terrestrial ecotoxicological
      methods of inhibiting seed germination and root elongation, the ecological risk
      of the DAT-IAT process for municipal wastewater treatment was assessed. The
      results of regular water-quality indices determination showed that COD and SS in
      treated wastewater by the DAT-IAT process could attain the National Integrated
      Wastewater Discharge Standard. Although NH4+-N could also meet the standard, most
      of nitrogen could not be removed out of the wastewater because of the N-form
      changing from NH4+-N to NO3(-)-N. Thus, the ecological risk of eutrophication
      could not successfully be reduced. The results based on the determination of
      ecotoxicological indices showed that IC50 of COD in wastewater from inflow water,
      DAT and effluent toxic to the germination of wheat seeds decreased gradually. The
      IC50 of the inhibitory rate of seed germination was 249.3 mg x L(-1), 165.3 mg x
      L(-1) and 161.2 mg x L(-1), respectively, and the IC50 of the inhibitory rate of
      root elongation was 257.6 mg x L(-1), 154.0 mg x L(-1) and 142.1 mg x L(-1),
      respectively. It thus revealed that the ecotoxicity of wastewater increased after
      treatment by the DAT-IAT process, which demanded more studies to address the
      regulation of the ecological risk. In particular, the inhibition of wheat root
      elongation was far more sensitive than the germination of wheat seeds under the
      same water-quality conditions. Thus, the root elongation could be recommended as
      a sensitive method to assess ecological risk of wastewater treatment effluents.

PMID- 19402487
TI  - [Effect of biofilm on the corrosion and fouling of cast iron pipe for water
      supply].
AB  - The crystalline phase and the element composition in the scales on cast iron pipe
      for drinking water was identified with XRD and XPS respectively to investigate
      the effect of biofilm existence on the corrosion and fouling of cast iron pipe.
      The total iron concentration in the water phase was measured simultaneously. The
      results showed that on 0-7 d the total iron concentration was higher in the water
      phase of the group with biofilm growth, but on 15-30 d it was higher in the water
      phase of the control without biofilm growth. The major peak of XRD patterns for
      the scales with biofilm growth was characterized as Fe oxide, while for the
      scales in the control it was always characterized as CaCO3. As presented by XPS
      atomic ratio, the Ca atomic percentage in the scales with biofilm growth was
      lower than that in the scales in the control, which might be contributed to the
      Ca2+ absorption by extracellular polymeric substances or Ca2+ consumption by
      microorganism growth. In comparison with that in the scales in the control, the
      iron atomic percentage in the scales with biofilm growth was higher on 7 d, while
      lower after 7 d. It can be concluded that on 0-7 d the existence of biofilm could
      promote the corrosion of cast iron pipe while inhibit corrosion after 7 d. The
      variance of major peak of XRD pattern and XPS atomic ratio indicated that biofilm
      had important effect on the configuration and composition of the scales of cast
      iron pipe. The corrosion inhibition of biofilm thus provided a new pathway to
      control the corrosion of metal pipes in drinking water distribution system.

PMID- 19402488
TI  - [Oxygen transfer efficiency of four kinds substrates applied in artificial
      aeration vertical-flow wetland].
AB  - In subsurface flow constructed wetlands, artificial aeration plays an important
      role in enhancing the ability of pollutant removal. Oxygenation capacity of four
      substrates, limestone, vesuvianite, 500 grade ceramisite and high-strength
      ceramisite, are tested under three kinds of gas volume [0.19, 0.38, 0.76 m3 x (m2
      x h)(-1)] in artificial aeration vertical-flow wetland. When the gas volume is
      0.19 m3 x (m2 x h)(-1), the results demonstrate that the oxygen utilization of
      500 grade ceramisite and high-strength ceramisite are highest as 14.39% and
      14.21%, and the oxygen utilization of limestone and vesuvianite are 11.68% and
      13.11% respectively. With the increase of aeration intensity, oxygen transfer
      efficiency parameter KLa rises accordingly. However, the oxygen utilization of
      vesuvianite and two other kinds of ceramisite decreases with the increase of
      aeration intensity. The oxygen utilization of vesuvianite, 500 grad ceramisite
      and high-strength ceramisite are lower as 7.67%, 10.46% and 10.77% respectively
      when the aeration intensity is 0.76 m3 x (m2 x h)(-1). On the contrary, the
      oxygen utilization of limestone get its maximum value of 14.04% as the aeration
      intensity is 0.38 m3 x (m2 x h)(-1).

PMID- 19402489
TI  - [Removal of algae using local soils and sediments].
AB  - Removal of algal blooms using modified local soils and sediments was studied. It
      was found that the local soils and sediments modified by chitosan removed algae
      effectively. The component of local soils and sediments, the organic matter in
      local soils and sediments had no effect on algae removal. Organic matter content
      (TOC < or = 40 mg/L) in water had a little negative effect on removal of algal
      cells. Field experimental results suggested that chitosan-modified local soils
      could be highly effective and quick for emergency needs to clear up harmful
      cyanobacterial blooms in fresh waters. In enclosures in Meiliang Bay of Taihu
      Lake, a loading of 0.025 g/L or 53 g/m2 chitosan-modified local soils removed
      98.6% chlorophyll-a while secchi depth increased from 15 cm to 90 cm.

PMID- 19402490
TI  - [Cultivation and nitrogen removal characteristics of deammonifition granules].
AB  - An SBR reactor seeded with anaerobic granular sludge was started up to enrich
      deammonifition bacteria and investigate its nitrogen removal characteristics.
      Research results showed that deammonification granular sludge could be cultivated
      successfully with firstly enriched ANAMMOX microorganisms in anaerobic condition
      and then controlled the dissolved oxygen in the SBR reactor between 0.3 and 0.5
      mg/L, in which the maximum total nitrogen removal rate reach 75.3%. When the Ca
      and P concentrations of the medium exceeded the necessary quantity, salt
      precipitation was observed and interfered with microbial activity and caused a
      decrease of the nitrogen removal rate of the reactor system. Salt precipitation
      was avoided by diminishing adequately the Ca and P concentrations of the medium
      during the following operation period, and the total nitrogen removal rate
      restored.

PMID- 19402492
TI  - [Comparison of biological phosphorus removal between different systems using O2,
      NO3(-) and NO2(-) as electron acceptors].
AB  - By parallel operation of three phosphorus removal systems (SBR) using different
      electron acceptors of O2, NO3(-) and NO2(-), process characteristics and inherent
      competition mechanism of microorganisms were discussed. Although NO2(-) had no
      direct inhibition on anoxic phosphorus uptake after the DPAO cultivation, system
      performance was still much lower than that with NO3(-) as electron acceptor. And
      it ultimately resulted from the washout of the group of DPAO (DPAO5) that lacked
      the ability to denitrify NO2(-) and the enhanced GAO growth in the system. Being
      the efficient electron acceptor, NO3(-) or O2 supplying SBRs removed phosphorus
      smoothly and comparatively, in viewpoint of stiochoimetry and constitution of
      functional bacteria. In all three test systems, mass of GAO was present to
      exhaust limited organics with PAO population. Moreover, total PAO could be
      divided into 6 distinct groups, i.e., PO, PN, Pn, PNn, PON and PONn, based on the
      abilities of utilizing different electron acceptors. And facultative PAO of PON
      and PONn were found as the main contributors for the phosphorus removal. The
      higher ratio they accounted in sludge, the more capacity the system possessed to
      remove phosphorus, i.e., SBR0 > SBRn5 > SBRn3.

PMID- 19402491
TI  - [Simultaneous nitrification and denitrification of membrane-aerated biofilm
      reactor].
AB  - A carbon membrane-aerated biofilm reactor was developed to treat municipal
      wastewater, in which the carbon and nitrogen were removed simultaneously. The
      results showed that COD removal, NH4+-N removal and TN removal efficiency could
      reach 82.5%, 95.1% and 84.2%, respectively, under the conditions of intra
      membrane pressure of 13.6 kPa, HRT of 14 h, influent COD and NH4+-N
      concentrations of 338 mg/L and 75 mg/L. However, in the last period during the
      operation of the reactor, the TN removal efficiency dramatically decreased
      because of the excessive growth of biomass on the nonwoven fiber, which also had
      serious negative effect on nitrification course. The microbiological community
      and spatial profiles were observed by fluorescence in situ hybridization and
      scanning electron microscopy. The anaerobic and anoxic bacteria were mainly
      located in the outer anaerobic region of the biofilm, while the aerobic ammonium
      oxidizing bacteria were mainly located in the inner aerobic region of the
      biofilm. The co-existing and coupling effect of aerobic nitrifying bacteria and
      anaerobic denitrifying bacteria provided the large biological potential for the
      simultaneous nitrification and denitrification in the carbon membrane-aerated
      biofilm reactor.

PMID- 19402493
TI  - [Effects of F/M on the uptake, storage and utilization of carbonhydrate in ASBR].
AB  - Substrate utilization in a glucose-fed anaerobic sequencing batch reactor (ASBR)
      under different F/M ratios was investigated. Glucose added was quickly taken up
      by fermentation bacterial in anaerobic digestion, then partly degraded directly
      to volatile fatty acid (VFA, accounted for 34%-38% of COD-fed) and partly
      accumulated transiently in the cell as glycogen (accounted for 41%-46% of COD
      fed) and degraded to VFA in the following. The bacterial accumulation capacities
      increased with F/M. The maximum specific storage capacities could reach as high
      as 116.8, 81.1 and 62.4 mg/g as F/M (COD/VSS) was controlled in 0.27, 0.20 and
      0.14 respectively. VFA production rate slowed down due to glucose storage, which
      resulted in low VFA accumulation and guaranteed a stable operation in ASBR under
      high loading rate.

PMID- 19402494
TI  - [Effect of different organic fraction on membrane flux declines].
AB  - Organic matter in the tap water was isolated into strongly hydrophobic acids,
      weakly hydrophobic acids, charged hydrophilic and neutral hydrophilic by DAX-8,
      XAD-4 and IRA-958 synthetic resins. Filtration tests using polyvinylidene
      fluoride (PVDF), polyethersulphone (PES) and cellulose acetate (CA) membranes
      were conducted to investigate the contribution of different organic fractions to
      membrane fouling. The results show that in filtration of raw water, flux declines
      with PES, PVDF and CA membrane are 67%, 59% and 19% of the initial flux,
      indicating that the more hydrophobic membrane resulted in more severe fouling.
      For the effect of different fractions on flux, flux decline with neutral
      hydrophilic is 41%-75% of the initial flux, whereas weakly hydrophobic acids is
      6%-33%, suggesting that neutral hydrophilic has a great impact on filtration
      flux. Among three membranes tested, CA membrane shows the lowest flux decline
      compared with other membranes in spite of rejection of as high as 14.69% of
      neutral hydrophilic, suggesting that the extent of flux decline may not be
      associated with the total amount of NOM removed. The mechanism of fouling was
      discussed and found that the neutral hydrophilic fraction with greater than 3 x
      10(4) of molecular weight caused a significant flux decline, through blocking the
      pore for the MF or UF having greater relative molecular mass cut-off (MWCO), but
      resulted in a little impact on flux with the UF having lower MWCO, through
      forming cake layer on the surface of membrane due to not entering the inside of
      pore.

PMID- 19402495
TI  - [Electrochemically reductive dechlorination of chloroform by palladium/polymeric
      pyrrole film/foam-nickel composite electrode in acidic system].
AB  - Palladium/polymeric pyrrole film/foam-nickel (Pd/PPy/foam-Ni) composite electrode
      were prepared by the electrodeposition method with the electrodepositing current
      density of 5 mA x cm(-2) and the electrodepositing time of 40 min.
      Electrochemical reductive dechlorination of chloroform in acidic system was
      investigated using the Pd/PPy/foam-Ni electrode at ambient temperature. The
      electrochemical deposition behaviors of Pd/PPy/foam-Ni electrode were studied by
      means of cyclic voltammetry (CV). Cyclic voltammetry results reveal that the
      large hydrogen adsorption peak current of -100 mA on Pd/PPy/foam-Ni electrode was
      obtained at about -500 mV (vs Hg/Hg2 SO4). SEM micrographs show that the addition
      of polymeric pyrrole changed the distributing configuration of Pd microparticles
      on the electrode and Pd/PPy/foam-Ni electrode possessed a good spatial extension.
      Chloroform dechlorination experimentes were conducted in acid system.
      Dechlorination experimental results indicate that, with the integrated analysis
      of removal efficiency and current efficiency, with the high current efficiency of
      44.17%, the removal efficiency of chloroform on Pd/PPy/foam-Ni electrode was
      49.23%, under the optimum conditions of the dechlorination current density of
      0.05 mA x cm(-2) and the dechlorination time of 180 min. In acid aqueous
      solution, with low initial concentration of chloroform, the results of
      dechlorination experiment were preferable.

PMID- 19402496
TI  - [Characteristics of sludge in treatment of high concentrated organic wastewater
      by swim-bed technology].
AB  - Based on the technology of conditional activated sludge process, swim-bed
      technology involving the novel biomass attachment material biofringe (BF) is one
      of the new and efficient advanced municipal wastewater treatments process. The
      process demonstrated effective treatment of high concentrated organic wastewater.
      When VLRs were from 1.7 kg/(m3 x d) to 4.5 kg/(m3 x d), 96% of average COD
      removal efficiencies and 80.7% of nitrification rate were achieved, respectively.
      The BF material allowed for attachment of large amounts of biomass. The mixed
      liquor suspended solid (MLSS) concentrations in the reactor reached 23 g/L at the
      highest during operation period, with holding 20-50 mL/g of SVI. An exponential
      law was found to be suitable to describe the variation of the viscosity as a
      function of MLSS. The granulation phenomenon of sludge was observed during the
      experiment. Protozoan and metazoans on the bio-film and suspended sludge were
      proved existing in the system by microscopic observation and DNA experiment.
      Observed sludge yields from 0.1046 to 0.1723 (MLSS/BOD) were obtained in swim-bed
      system.

PMID- 19402497
TI  - [Influences of inorganic anions on oxidation of phenol by CuO-H2O2].
AB  - Phenol was selected as a model pollution substrate. The influences and mechanism
      of inorganic anions on its oxidation were investigated in neutral solution at low
      temperature and atmospheric pressure. Results showed that phenol could be removed
      efficiently by CuO and H2O2 with 94.7% removal rate in 10 min, which followed
      hydroxyl radical oxidation mechanism. Inorganic anions influenced the oxidation
      with different mechanisms. Higher concentration would lead to more significant
      influences. HCO3(-) accelerated the inefficient decomposing of H2O2. The
      decomposing rate constants increased from 0.3738 min(-1) at concentration of 0
      mmol x L(-1) to 0.5347 min(-1) at concentration of 20 mmol x L(-1). The TOC
      removal rate constants decreased from 0.267 min(-1) to 0.0194 min(-1)
      correspondingly. HPO4(2-) retarded the H2O2 decomposing and inhibited the phenol
      oxidation. The decomposing rate constants of H2O2 and the removal rate constants
      of TOC decreased from 0.3738 min(-1), 0.267 min(-1) to 0.0338 min(-1), 0.0338
      min(-1) respectively. Cl(-) was good at H2O2 decomposing and phenol removal with
      simultaneously increasing the H2O2 decomposing rate constants and the TOC removal
      rate constants from 0.3738 min(-1), 0.267 min(-1) to 0.6040 min(-1), 0.3879 min(
      1) respectively. NO3(-) and SO4(2-) had few influences on H2O2 decomposing and
      phenol removal.

PMID- 19402498
TI  - [Degradation of MC-LR by combination of UV/H2O2 process].
AB  - The degradation of MC-LR in water by UV/H2O2 process was investigated. The
      effects of intensity of UV radiation, initial concentration of MC-LR, dosages of
      H2O2, initial pH value and anions on degradation of MC-LR by UV/H2O2 process were
      studied. The results show that the removal of MC-LR only by H2O2 is nearly zero,
      and UV process can degrade MC-LR to a certain extent. However, the degradation
      efficiency of UV/H2O2 process is much higher than UV and H2O2 process due to the
      synergetic effect between UV and H2O2. The removal of MC-LR increases with the
      enhancement of intensity of UV radiation, but decreases gradually with the
      increase of initial concentration of MC-LR. When the dosages of H2O2 change from
      1 mmol/L to 3 mmol/L, the constant of degradation rate rises from 0.0844 to
      0.1664. The optimum pH value is 3.13. The added anions have adverse effect on the
      degradation of MC-LR, especially carbonate and nitrate ions have the biggest
      influence among the studied anions.

PMID- 19402499
TI  - [Adsorption property of chitosan composite resin for nitrite-nitrogen].
AB  - A novel composite resin of chitosan supported by activated carbon was prepared
      using the emulsification cross-linking technique. The adsorption properties of
      the resin for NO2(-)-N were studied. It is found that there are many developed
      micropores on the surface of the resin. Due to the addition of activated carbon,
      the bulk density, skeleton density and void ratio of composite resin are lower
      than those of the chitosan resin.The adsorption capacity of chitosan composite
      resin is much greater than the simple compounding made up of activated carbon and
      chitosan resin. When the temperature is lower than 40 degrees C, the adsorption
      is a physisorption process primarily caused by electrostatic attraction. The
      adsorption selectivity of composite resin for NO2(-)-N is affected by the
      concentration and negative charge number of co-existing anions. The adsorption
      reachs equilibrium in 60 min with a calculated equilibrium capacity of 0.479
      mg/g. The adsorption velocity is high while the adsorption capacity is low. When
      the temperature is higher than 40 degrees C, the adsorption is a chemisorption
      process which is endothermic, spontaneous and entropy increasing. The adsorption
      reached equilibrium in 90 min with a calculated equilibrium capacity of 0.700
      mg/g. The adsorption velocity drops while the adsorption capacity increases. The
      chemisorption and physisorption isotherm equations are conformed to the
      Freundlich model, and the adsorption process accords with second-order kinetic
      rate mode.

PMID- 19402500
TI  - [Recovery and reuse of SDS by ultrafiltration with acid or chelator].
AB  - The retentate stream containing Cd2+ was chosen for the investigation. Effects of
      acid reagent, chelator, pH and operation mode on separation of Cd2+ and recovery
      of SDS, as well as efficiency of reclaimed SDS were investigated. The optimum
      conditions in acidification were obtained: H2SO4 as acid reagent, pH = 1.0,
      operation mode of batch. Under these conditions, separation of Cd2+ and recovery
      of SDS are 98.0% and 58.1%, respectively. And the efficiency of reclaimed SDS for
      removing Cd2+ is 80.2%. In chelation, the optimum conditions were investigated:
      EDTA as chelator, uncontrolled pH (pH = 4.4) and operation mode of batch. Under
      these conditions, separation of Cd2+ and recovery of SDS are 90.1% and 60.5%,
      respectively. And the efficiency of reclaimed SDS for removing Cd2+ is 79.4%.

PMID- 19402501
TI  - [Extracellular polymeric substances disintegration by Fenton oxidation of excess
      sludge].
AB  - Fenton oxidation was used to disintegrate extracellular polymeric substances
      (EPS) of excess sludge with its strong oxidation ability. The concentration of
      polysaccharide, protein and the change of soluble chemical oxygen demand (SCOD)
      disintegrated from EPS represent the EPS disintegration degree. The objective of
      this study is to optimize the operational conditions for EPS disintegration with
      Fenton oxidation. It is shown that the optimal operational condition is as
      following: pH = 2.5, reaction time = 90 min, H2O2/Fe2+ (weight dosage ratio) =
      8:1 and reaction temperature is about 65-70 degrees C. Under this condition after
      the Fenton oxidation, SCOD, concentration of polysaccharide, protein in the
      supernate increase from 45.88, 10.96 and 11.99 mg x L(-1) to 684.93, 382.17 and
      302.62 mg x L(-1), respectively; the average diameter and the median diameter of
      sludge particulates reduce from 838.89 microm and 859.20 microm to 137.22 microm
      and 148.69 microm, respectively. As a result, EPS is effectively disintegrated by
      Fenton oxidation and the sludge is greatly mineralized, which benefits the
      further sludge reduction and utilization.

PMID- 19402502
TI  - [Biodegradation of [omim][PF6]].
AB  - Acclimatized the activated sludge with [omim][PF6] which was used as the C, N, P
      resources for microbe, the biodegradation ratio of [omim][PF6] with different
      inoculants which were acclimatized or not was investigated. And the influence of
      appending an ester in the side chain of the imidazolium cation on the
      biodegradation of [omim][PF6] was discussed in the same conditions. The
      biodegradation pathways of [omim]+ were analyzed. The results showed that the
      biodegradation of ionic liquids was improved by appending an ester in the side
      chain; the biodegradation rate of [omim][PF6] was less than 20% when the
      inoculant was original activated sludge, which was not referred as "readily
      biodegradable"; [omim][PF6] would stay in environment for a long time; the
      biodegradation ratio reached 60% when the inoculant was acclimatized activated
      sludge; 1-methyl-imidazolium was residual in the course of biodegradation of
      [omim]+, the semifinished products of biodegradation of [omim]+ was analyzed by
      HPLC-MS/MS and the pathways were presumed.

PMID- 19402503
TI  - [Buffer capacity of aquifer media polluted by landfill leachate].
AB  - A column filled with fine sand was constructed to investigate pH buffering
      capacity and redox buffering capacity of aquifer media. Experimental results
      indicated that calcium carbonate played a significant role in pH buffering; with
      the aggravating of landfill leachate pollution, the pH buffering capacity of
      calcium carbonate was increased; it increased from background value, which was
      1.62 x pH(-1) mmol/kg, to 41.3 x pH(-1) mmol/kg. With the aggravating of landfill
      leachate pollution, the oxidation capacity (OXC) of aquifer media was decreased,
      and the reduction capacity (RDC) was increased. In unpolluted aquifer media, Fe3+
      was the main component of OXC, and accounted for about 70.5% of OXC; TOC was the
      main component of RDC, and accounted for about 98.7% of RDC. Species of the
      minerals was related to the degree of pollution; large fraction of amorphous Fe3+
      and part of crystalline Fe3+ were reduced near the pollution source, and the
      reduced product was mainly precipitated as FeCO3 and FeS. Deposit of produced
      Fe2+ led to ion-exchangeable Fe2+ content increased from 0.5% of uncontaminated
      aquifer media to 3%. Therefore, Fe3+ may act as a very significant redox buffer
      in aquifer.

PMID- 19402504
TI  - [Salt effects on treatment performance and microbial community structure in
      MUCT].
AB  - It is essential for a full-scale treatment plant processing saline wastewater to
      understand the effects of salt on an activated sludge system and the performance
      of pollutant removal. For this purpose, a bench-scale modified university of cape
      town (MUCT) process was tested to treat real saline sewage with salt
      concentrations of 5, 8, 10 and 15 g/L. The experimental results indicated that
      salt in sewage significantly affected nutrient removal compared with organic
      removal. Total phosphorous removal efficiency in MUCT deceased from 92% when
      treating freshwater to 72% when treating 8 g/L saline wastewater, while total
      nitrogen removal efficiency decreased from 75% to 62%. Vital number of aerobic
      heterotrophic bacteria shrunk when salt concentration in wastewater was over 15
      g/L, resulting in decreased organic removal efficiency. Obvious nitrite
      accumulation in the aerobic tank and denitrifying nitrite by polyphosphate
      accumulating organisms (PAOs) in the anoxic tank occurred in the MUCT treating
      saline sewage containing over 8 g/L NaCl. Elevated salt level enhanced the carbon
      requirement for phosphorus release. Population shift in biological community
      (aerobic-heterotrophic, nitrifying, and denitrifying organisms) in treatment
      system was observed in response to salinity inhibition, which contributed to an
      insight into the nature and the magnitude of the salt effects.

PMID- 19402505
TI  - [Effect of DO and aeration/non-aeration ratio on the microbial community
      structure in one-step SBBR completely autotrophic nitrogen removal process].
AB  - To analyze the effect of DO and aeration/non-aeration ratio on the microbial
      community structure, active sludge and biofilm samples were taken from the SBBR
      one-step completely autotrophic nitrogen removal reactor under different DO
      concentrations and aeration/non-aeration ratios. By PCR-DGGE and bands
      statistical analyses, results show that through one and a half year of operation,
      the microbial community structures in this system has changed a lot compared with
      the inoculum. The bacterial richness values of biofilm are higher than active
      sludge in 2 h:2 h aeration/non-aeration ratio, no matter when moderate, high and
      low DO concentration. When this system is operated under the most efficient
      condition: DO = 2.0 (aeration) mg/L, 0.4 (non-aeration) mg/L, the bacterial
      richness values are the highest. There are about 14 and 10 bands in the biofilm
      and active sludge samples respectively. The diversities of bacterium and their co
      metabolisms are the key factors of maintaining a high operate efficiency. In
      addition, the aeration/non-aeration ratio also has the influence on the microbial
      community structure. Under long aeration/non-aeration ratio of 3 h:5 h, microbial
      community structure of biofiln is similar with active sludge. The comparability
      is 100%. The activities of aerobic and anaerobic bacterium have lost much that
      makes low efficiency of this system although they could survive both in active
      sludge and biofim.

PMID- 19402506
TI  - [Analysis of characteristics of microbial communities in membrane bioreactor and
      conventional activated sludge process].
AB  - A submerged MBR and CAS were used for municipal wastewater treatment to
      investigate their performance and the microbial community. The effluent COD
      concentrations of MBR and CAS were 39.6 mg/L and 62.9 mg/L on average,
      respectively. The effluent concentrations of NH4+-N in MBR and CAS were 6.8 mg/L
      and 14.5 mg/L on average, respectively. MBR demonstrated a more stable and
      excellent effluent quality than CAS. The microbial community in the MBR and CAS
      indicate a clear difference in despite of same inoculation due to operation
      conditions of the MBR with the lower F/M ratio, accumulation of inert substance
      and strong shear force in aeration. The results of DGGE indicate that the
      quantity of the bacteria and the change of the similarities coefficient of the
      microbial community in MBR are more than those in the CAS. The result of DGGE
      showed that the quantity of bacteria in MBR is always larger than that in CAS, on
      15, 124, 186 and 230 d, the quantity of lanes are 22, 25, 24 and 20 in MBR and
      19, 14, 17 and 20 in CAS, respectively. The Dice similarity index are 54.1%,
      63.7%, 63.9% and 66.8% in MBR and 71.8%, 61.4%, 9.1% and 65.9% in CAS,
      respectively. These phenomena show that the discharge of the excess sludge from
      CAS results in a loss of some no-selective bacteria, and the microbial community
      in the MBR has higher capability acclimatized the environment variable than that
      in the CAS. According to the Dice coefficient of the microbial community was
      higher and higher during the whole operation, it was influenced by the changes of
      environments, e.g. influent concentration, temperature and so on.

PMID- 19402507
TI  - [Marine SRB community reducing sulfate wastewater in flue gas desulfurization].
AB  - An SRB community (SRB-2) was enriched from marine sediment for the treatment of
      sulfate-rich wastewater of high salinity, and the effect of salinity,
      temperature, pH value, carbon source, concentration of sulfate and the form of Fe
      on the activity of SRB-2 was studied. The results show that SRB-2 is a
      halophilous and moderately mesophilous SRB community. The optimal conditions for
      its growth are as follows: temperature of 30-40 degrees C and pH value of 7.4
      8.3; it can endure 5,200 mg/L SO4(2-) and 60g/L NaCl. Zero-valent Fe can promote
      the reductive activity of SRB-2, while Fe2+ inhibits that. SEM and optical
      microscopic measurements indicate many rod-shaped and spiral bacteria on the
      surface of padding in reactor and black sticky substance composed of rod-shaped
      bacteria on the bottom of reactor. This sticky substance might be cumulus of
      culture SRB-2-64 (GenBank accession number: EU167911).

PMID- 19402508
TI  - [Biodegradation of di-n-butyl phthalate by Pseudomonas aeruginosa].
AB  - A new small capacity-wide extraction method was proposed for detection of its
      biodegradation in water. Results showed that the halflife (t1/2) of di-n-butyl
      phthalate (DBP) biodegradation was 3.60 day when the concentration of DBP was 400
      mg/L and the biomass concentration was 2 g/L. The biodegradation process
      conformed to the first-order kinetic model. Moreover, the whole degradation
      process could be divided into several steps: adsorption, desorption and
      degradation. Two metabolites of DBP degradation were identified as mono-butyl
      phthalate and phthalic acid by gas chromatography-mass spectrometry, which
      confirmed the dioxygenate process during the hydrolysis of DBP.

PMID- 19402509
TI  - [Stress and biological response of naphthalene on the antioxidant defense system
      in visceral mass of zebrafish (Danio rerio)].
AB  - With the acute toxicity test, we obtained the median lethal concentration (LC50)
      of naphthalene to the zebrafish for 96 h, which was 11.8 mg x L(-1). Then we set
      up five treatments(0, 1/6 LC50, 1/4 LC50, 1/3 LC50 and 1/2 LC50) and exposed
      zebrafish to these treatments for 0.5, 1, 2, 4, 7 and 14d respectively to study
      the effects of naphthalene on the antioxidant defense system in visceral mass of
      zebrafish. The results showed that GSH, GPx and GST were very sensitive to
      naphthalene and were inhibited or induced at 0.5 d exposure. The activities of
      GPx were induced on the whole after 0.5 d, but were inhibited at higher
      concentration treatments (1/3 LC50 and 1/2 LC50 treatments) at 14 d exposure;
      while the activities of GST and the contents of GSH were almost lower than that
      of the control. The activities of SOD were induced first and then inhibited after
      2 d; the activities of CAT were inhibited almost in the all treatments after 1 d.
      The effects of naphthalene on the antioxidant defense system in visceral mass of
      zebrafish could be used as biomarkers to estimate the biological effect of fish
      exposed to polycyclic aromatic hydrocarbons.

PMID- 19402510
TI  - [Bioaccumulation and toxicity test of diethylstilbestrol to zebrafish (Danio
      rerio) embryo].
AB  - The bioaccumulation regulation and the toxicity of diethylstilbestrol (DES) were
      studied on zebrafish (Danio rerio) embryos with the methods of HPLC and early
      life stage test, and the toxic mechanisms were also discussed with the techniques
      of quantitative structure-activity relationship (QSAR) and gene chips. After the
      zebrafish embryos exposed at 0.2 mg x L(-1) DES for 24, 48 and 72 h, the body
      levels of DES in zebrafish embryo were (25.78 +/- 4.95), (54.88 +/- 7.10) and
      (71.93 +/- 10.55) microg/g, respectively. Even exposure started at different time
      (0 hpf and 8 hpf), the most sensitive sub lethal endpoints were both 72 h delayed
      hatch, and the EC50 values for them were (0.14 +/- 0.09) and (0.33 +/- 0.14)
      mg/L, so that zebrafish embryo was more sensitive to the exposure of DES before
      the stage of gastrula (8 h after fertilization). QSAR studies found when compared
      with other phenol-endocrine disrupts, DES was much more toxic, and this related
      to its higher TE value (52.1217 eV). Meanwhile, when adult zebrafish exposed at 5
      microg/L DES for 21 d, it was found by the gene chips that parts of gene
      expressions would be changed and the genetic toxicity of DES was approved. DES
      was concluded to be developmental and genetic toxic to zebrafish, and the
      biochemical reaction-associated process might be the key parameter in determining
      the toxicity level.

PMID- 19402511
TI  - [Photosynthetic damage induced by elevated O3 in two varieties of winter wheat
      with free air controlled enrichment approach].
AB  - O3-FACE (ozone-free air controlled enrichment) platform has been established for
      observing the photosynthetic damage induced by elevated O3 in functional leaves
      of two winter wheat (Tritcium aestivum L.) varieties (Yangmai 16 and Yannong 19)
      during grain filling stage. The results showed that the response trend of all the
      parameters was similar: (1) The net photosynthetic rate (Pn) decreased gradually
      and after 35 days of O3 treatment, Pn decreased by 56.21% and 21.82% for Yannong
      19 and Yangmai 16, respectively. (2) Chlorophyll fluorescence kinetics parameters
      changed as decreased in Fv/Fm (maximal photochemical efficiency of PS II in the
      dark), qp (photochemical quenching), Phiexe (excitation capture efficiency of PS
      II or intrinsic PS II efficiency), PhiPSII (actual photochemical efficiency of PS
      II in the light), and increased in NPQ (non-photochemical quenching); Energy
      distribution parameters changed as rose in % D (fraction of light absorbed in PS
      II that is dissipated in the PS II antenna), reduced in % P (fraction of light
      absorbed that is used in photochemistry), and no significant changed in % X
      (fraction of light absorbed that is not used or dissipated in the PS II antenna).
      After 35 days of O3 treatment, the actual photochemical efficiency of PS II of
      Yannong 19 and Yangmai 16 were reduced by 24.42% and 9.97%, respectively.(3) It
      was declined in Chlt/Car (total chlorophyll content/carotinoid content) while the
      ratio of Chla/Chlb (chlorophyll a content/chlorophyll b content) was increased.
      There was a growth in Mg2+, Ca2+-ATPase, activities and ATP contents in
      chloroplast. The extent of variation in the above parameters and the differences
      between the two varieties were enlarged as the O3 treatment time increasing and
      it could be found a more serious damage effect in Yannong 19 than that of in
      Yangmai 16. In conclusion, the responses of the capacities of defense and repair
      systems of the two varieties to elevated O3 were reflected by increase in heat
      dissipation, changes in contents and composition of photosynthetic pigments, and
      enhancement in the ATP (ATP enzyme) activities in chloroplast. With the time of
      O3 treatment elongating, there was an accumulation effect of 03 damage to wheat
      and a great different tolerance between the two varieties was observed.

PMID- 19402512
TI  - [Relation between average oxidation state of Mn of birnessite and the amount of
      Pb2+ adsorbed].
AB  - Vacant sites in Mn oxides, commonly occur in soils, play an important role in
      their heavy metal adsorption behavior. The dependence of Pb2+ adsorption capacity
      for the synthesized birnessites and their d110-interplanar spacing on the
      respective Mn average oxidation state (AOS), and the relationship between Pb2+
      adsorption and the Mn2+, H+, K+ released during adsorption were investigated. The
      results show that Mn AOS of birnessites apparently reflects their amount of
      vacant sites which largely account for the Pb2+ adsorption. Significant positive
      correlation between Pb2+ adsorption capacity and the Mn AOS of corresponding
      birnessites (r = 0.9779 > 0.6614, n = 14, alpha = 0.01), negative correlation
      between d110 spacing and the Mn AOS (r = -0.9035 < -0.6614, n = 14, alpha =
      0.01), and significant positive correlation between Pb2+ adsorption and the Mn2+,
      H+, K+ released during adsorption(r = 0.9962 > 0.6614, n = 14, alpha = 0.01) are
      found. The vacant sites amount increases with Mn AOS for birnessites, which
      causes the increase of Pb2+ adsorption. Therefore, the Pb2+ adsorption capacity
      of birnessite is largely determined by the amount of vacant sites, from which
      Mn2+, H+, and K+ released during adsorption are mostly derived.

PMID- 19402513
TI  - [Distribution of organochlorine pesticides in soils in Haihe River and Haihe
      Estuary area, China].
AB  - Levels and distribution of organochlorine pesticides (OCPs) were investigated in
      soils along Haihe River and in Haihe Estuary area. 31 surface soil samples were
      collected on August 2007, and they were extracted using accelerated solvent
      extraction. The HCHs and DDTs contents in soils were determined by gas
      chromatography with an electron capture detector (GC-ECD). The results show that
      the concentrations in soils range from n.d. to 1,728 microg x kg(-1) with a mean
      value of 93.9 microg x kg(-1) for HCH congeners, and from n.d. to 288 microg x
      kg(-1) with a mean value of 34.4 microg x kg(-1) for the sum of p,p'-DDT, o,p'
      DDT, DDE, and DDD, respectively. The HCHs is dominant, accounting for 72 percent
      of total OCPs content. The working hypothesis is that OCPs levels and
      distribution in the area are dependent on the degree of anthropogenic
      intervention. Higher concentrations of total OCPs are found in the chemical
      industrial region, and ones from Haihe River area are higher than Haihe Estuary
      area, due to impact from chemical industrial emissions. According to the isomers
      of HCHs and metabolites of DDTs, HCHs and DDTs in soils in this area may be
      derived from the use of pesticide in agricultural and industrial emissions in
      history, though having recent inputs of OCPs at a few sites. Compared with those
      in other national or international regions, the concentrations of HCHs and DDTs
      in soils from Haihe River area are higher. It can be concluded that soil OCPs
      levels are relatively high in this area.

PMID- 19402515
TI  - [Microwave thermal remediation of soil contaminated with crude oil enhanced by
      granular activated carbon].
AB  - The advantage of rapid, selective and simultaneous heating of microwave heating
      technology was taken to remediate the crude oil-contaminated soil rapidly and to
      recover the oil contaminant efficiently. The contaminated soil was processed in
      the microwave field with addition of granular activated carbon (GAC), which was
      used as strong microwave absorber to enhance microwave heating of the soil
      mixture to remove the oil contaminant and recover it by a condensation system.
      The influences of some process parameters on the removal of the oil contaminant
      and the oil recovery in the remediation process were investigated. The results
      revealed that, under the condition of 10.0% GAC, 800 W microwave power, 0.08 MPa
      absolute pressure and 150 mL x min(-1) carrier gas (N2) flow-rate, more than 99%
      oil removal could be obtained within 15 min using this microwave thermal
      remediation enhanced by GAC; at the same time, about 91% of the oil contaminant
      could be recovered without significant changes in chemical composition. In
      addition, the experiment results showed that GAC can be reused in enhancing
      microwave heating of soil without changing its enhancement efficiency obviously.

PMID- 19402514
TI  - [Influences of cation species on adsorption and desorption of oxytetracycline in
      two typical soils of China].
AB  - On the basis of the OECD Guideline 106, batch sorption methods were employed to
      reveal the effect of different cations (0.01 mol x L(-1) Ca2+, K+ and Na+) on
      oxytetracycline (OTC) adsorption and desorption process in two tested soils
      (cinnamon soil and red soil). Results show that the Freundlich model is the best
      isotherm to describe the experimental data of adsorption and desorption, and the
      average fitting correlation coefficient is 0.989. Except for the adsorption
      isotherm of cinnamon soil on OTC in 0.01 mol x L(-1) KCl, the other isotherms
      resemble the L-type curves. To the same cation, OTC adsorption capacity (lgKf) in
      the red soil (ranging from 2.907 to 3.173) is always higher than in the cinnamon
      soil (ranging from 2.577 to 2.885), and the adsorption strength (1/n) in the red
      soil (ranging from 0.672 to 0.825) is always lower than the cinnamon (ranging
      from 0.713 to 1.005). The dominant mechanism is physical adsorption in two soils.
      To the same soil, cation species don't affect OTC adsorption capacity (lgKf) (p >
      0.05). And Ca2+ can reduce significantly the adsorption strength (p < 0.05),
      comparing with K+ and Na+. The apparent adsorption-desorption hysteresis is
      found, and the average hysteresis index (HI) in all soils are from 0.015 to
      0.053. To the same cation, OTC HI is significantly higher than that of red soil
      (p < 0.05). In cinnamon soil, there is significantly HI difference (p < 0.01)
      between K+ and Ca2+, Na+. However, three cations have no significantly difference
      effect on HI in red soil.

PMID- 19402516
TI  - [Electricity generation from corn steepwater using microbial fuel cell
      technology].
AB  - Corn steepwater containing 49,732.2 mg/L of chemical oxygen demand (COD) was used
      as fuel for a membrane electrode assembly microbial fuel cell (MEA-MFC), which
      could generate electricity and treat the wastewater at the same time. During a
      batch experiment of 94 days with a fixed 1,000 Omega external resistance, the
      maximum voltage output of 525.0 mV and power density of 169.6 mW/m2 were obtained
      after 17 days, corresponding to the current density, internal resistance and open
      voltage of 440.2 mA/m2, 350 Omega and 619.5 mV, respectively. However, data
      showed that the coulombic efficiency was only 1.6%, suggesting very limited COD
      was utilized for electricity generation. At the conclusion of the test, the
      removals of COD and ammonia-nitrogen were achieved 51.6% and 25.8%, respectively.
      This study demonstrates that corn steepwater can be used for power generation in
      MFC with simultaneous accomplishments of wastewater treatment, providing a novel
      approach for the safe disposal and recycle of corn steepwater.

PMID- 19402517
TI  - [Patterns of PCDD/Fs, PCBs and PCNs homologues in fly ash from cement kilns].
AB  - The concentrations and toxic equivalent (TEQ) values of PCDD/Fs, PCBs and PCNs in
      fly ash collected from three types of cement kilns (vertical shaft kiln, wet
      process rotary kiln and dry-process rotary kiln) and two types of waste
      incinerators were determined, and the patterns of homologues and congeners were
      compared. The results showed that the total TEQ of PCDD/Fs, PCBs and PCNs in
      cement kiln fly ash, which were in the range of 4.0-62, 0.069-3.9 and 0.47-2.8 ng
      x kg(-1) respectively, were much lower than that of fly ash from waste
      incinerators. In cement kiln fly ash, the predominating PCDD/Fs homologues were
      TCDFs, and the chief 2, 3, 7, 8-PCDD/Fs congeners were OCDD, 2, 3, 7, 8-TCDF and
      1, 2, 3, 4, 6, 7, 8-HpCDF. The patterns of PCBs homologues in cement kiln fly ash
      were similar to those of waste incinerators in which TeCB were predominating
      homologues. PCB77, PCB105, PCB118 were at higher concentrations than other co
      polar PCBs. Different types of cement kiln fly ash presented similar PCNs
      homologue patterns. The predominant homologues were TeCN, whereas OcCN were not
      detected. PCN 66/67 which has dioxin like toxity was the most abundant congener
      in all fly ash.

PMID- 19402518
TI  - [Formation and reactions of biogenic manganese oxides with heavy metals in
      environment].
AB  - Manganese (Mn) oxides are common minerals in natural environments that may play
      an important role in the biogeochemical cycles of heavy metals. Increasing
      evidences have shown that Mn (II) oxidation is a microbially-mediated process,
      and the Mn oxidizing microorganisms are thus recognized as the major drivers of
      the global Mn cycle. The major pathway for bacterial Mn (II) oxidation is
      catalysed by a multicopper oxidizing enzyme family. The primary Mn (IV) biooxides
      are phyllomanganate-like minerals most similar to delta-MnO2 or acid birnessite.
      Manganese oxides are known to have high sorption capacities for a wide variety of
      metal ions and considered to be the important environmental oxidant to many metal
      ions. This paper reviewed the mechanisms of biogenic manganese oxides formation
      and their reactions with heavy metal ions in environment.

PMID- 19402519
TI  - [Review on the tastes and odors compounds in drinking water of China].
AB  - Tastes and odors problems (T&Os) in China and studies on T&Os are reviewed,
      especially on aspects of the present situation in China, sources of T&Os in
      water, T&Os qualitative & quantitative technology, odorant composing characters,
      removal technologies and processes on typical odorant in drinking water. This
      review aims to elucidate that besides microbial metabolism product such as
      geosmin and 2-MIB, organic anaerobic decomposition product such as thiol
      thioether were also main odorant in drinking water of China. Thiol-thioether
      odorant which was found in drinking water of Dongguan in 2006 for the first time,
      was proved to be the main odorant in Taihu Lake drinking water risk in 2007 as
      well. Geosmin and 2-MIB were more easily removed by adsorption than oxidation,
      but thiol-thioether was easily removed by oxidation not by adsorption. In order
      to cope with T&Os in different water source, different season and different
      odorant,studies on odorant composing character, removal technology, mechanism and
      process of typical odorant should be carried out as soon as possible in China.

PMID- 19402520
TI  - [Pollution characteristics of n-alkanes in atmospheric fine particles during
      Spring Festival of 2007 in Beijing].
AB  - Research PM2.5 aerosols had been carried out with sampler of high-volume sampler
      during Spring Festival of 2007 in Beijing, and the concentrations of n-alkane in
      PM2.5 samples were determined via GC-MS. The average concentrations of PM2.5
      which were all exceeded WHO threshold values were higher in the night than those
      in the day time. The n-alkane homolog from C10 to C33 were detected with the
      major peak carbon numbers ranging from 23 to 25. The total concentrations of n
      alkane were higher in the night (943.5 ng x m(-3)) than those in the day time
      (581.1 ng x m(-3)). And also we found that the average concentrations of n
      allkane before New Year's Eve (1,025.5 ng x m(-3)) were higher than those after
      (536.6 ng x m(-3)). The CPI values were 0.9-1.4 with average of 1.15. Those
      results may mean that primary resource of n-alkane in fine particles was the
      incomplete combustion of fossil fuel. The percent contribution of leaf "Wax" n
      alkane indicated that about 8.5%-47% of n-alkane came from waxy leaf surface
      abrasion.

PMID- 19402521
TI  - [NH4+-N removal stability of zeolite media packed multistage-biofilm system for
      coke-plant wastewater treatment].
AB  - The practical ammonia stripping effectiveness of coke-plant wastewater treatment
      may vary widely, and high NH4+-N shock loading will lead to the fluctuation of
      residual NH4+-N concentration of biological effluent. A zeolite media packed
      multistage-biofilm system (ZMBS) was used for coke-plant wastewater treatment for
      enhancing the NH4+-N treatment ability of the bio-system to shock loading, as
      well as achieving high COD removal efficiency. Treatment performance during
      steady-state and shock loading and transformation of organic pollutants in the
      system were investigated systematically. The experiment results indicated that
      when the system was operated at NH4+-N loading 0.21 kg/(m3 x d) and COD loading <
      or = 1.35 kg/(m3 x d), the average effluent NH4+-N and COD concentrations were
      (2.2 +/- 1.2) mg/L, (228 +/- 60) mg/L with average removal efficiencies of (99.1
      +/- 0.5)% and (86.0 +/- 2.6)%. During the twice NH4+-N shock loadings [0.03
      kg/(m3 x d) and 0.06 kg/(m3 x d)], ZMBS showed a strong resisting ability with
      average removal efficiencies of 99.0% and 92.9% higher than those of a compared
      system's 96.8% and 89.3%. By monitoring the change of water quality along the
      length of the ZMBS's cells, two function zones for different pollutant removal
      were found to exist, named as decarbonization/nitrification (C/N) zone and
      nitrification (N) zone, and the NH4+-N removal rate in N zone was 2-8 times as
      that in C/N zone. TOC concentrations of organic matters with relative molecular
      weight < 1 x 10(3), 1 x 10(3) to 1 x 10(4), and > 1 x 10(4), were 227.6, 104.8
      and 35.0 mg/L in raw wastewater, and 31.2, 22.9 and 31.5 mg/L in the effluent,
      respectively. Organic matters with relative molecular weight < 1 x 10(3) and 1 x
      10(3) to 1 x 10(4) in raw wastewater were removed effectively by ZMBS, but those
      with relative molecular weight > 1x 10(3) were the main remained substances in
      the effluent.

PMID- 19402522
TI  - [Electrochemical degradation of sodium pentachlorophenol on a Pd/C gas-diffusion
      electrode].
AB  - Pd/C catalyst was prepared by hydrogen reduction method and used for the Pd/C gas
      diffusion electrode. It was characterized by cyclic voltammetry (CV) techniques.
      The electrochemical degradation of sodium pentachlorophenol (PCP-Na) was
      investigated in a diaphragm electrolysis device, feeding firstly with hydrogen
      gas then with air, using the Pd/C gas-diffusion electrode and the
      carbon/polytetrafluoroethylene (C/PTFE) gas-diffusion electrode as the cathode,
      respectively. The results indicate that the two-electron reduction from O2 to
      hydrogen peroxide (H2O2) is produced at the Pd/C gas-diffusion electrode, and the
      accumulated H2O2 in the cathodic compartment reach to the steady concentration of
      9.8 mg/L after 100 min. The Pd/C gas-diffusion cathode can reductively
      dechlorinate PCP-Na by feeding hydrogen gas, and accelerate the two-electron
      reduction of O2 to hydrogen peroxide (H2O2) by feeding air. Therefore, both the
      removal efficiency and the dechlorination degree of PCP-Na exceed 80% after 100
      min, and the average removal efficiency of PCP-Na in terms of total organic
      carbon (TOC) exceeds 75% after 200 min by using Pd/C gas-diffusion cathode,which
      is better than that of the C/PTFE gas-diffusion cathode. High performance liquid
      chromatography (HPLC) allows identifying phenol as the dechlorination product.

PMID- 19402523
TI  - [Cloning and quantitative expression of chlorocatechol 1,2-dioxygenase gene].
AB  - The chlorocatechol 1,2-dioxygenase gene, designated as tcbC (J5-2) (GenBank
      Accession No. EF111021), was cloned from total DNA of Pseudomonas aeruginosa J5-2
      which can degrade 1,2,4-trichlorobenzene. The deduced amino acid sequence
      analysis of tcbC (JS-2) shows that it is different from tcbC (P51) cloned from
      another 1,2,4-trichlorobenzene-degrader Pseudomonas sp. P51. tcbC (J5-2) is only
      95% similar to tcbC (P51) at the amino acid level.Three critical amino acid
      residues in tcbC (J5-1) are Leu-48, Ala-52, and Ile-73. Otherwise, they are Val
      48, Ala-52, and Met-73 in tcbC (P51). mRNA accumulation of tcbC in J5-2 was
      quantified by real-time reverse transcription-PCR, when J5-2 grew on 1,2
      dichlorobenzene, 1,3-dichlorobensene and 1,2,4-trichlorobenzene respectively. The
      results show that 1,2, 4-trichlorobenzen is a better inducer than 1,2- and 1,3
      dichlorobensene.

PMID- 19402524
TI  - [Assessing bioaccumulation and bioavailability of PAHs and OCPs in water using
      sediment, rare minnow and biomimetic sampler].
AB  - Accumulation of polycyclic aromatic hydrocarbons (PAHs) and organochlorine
      pesticides (OCPs) in different phases in water was assessed in a wetland in
      Guanting, Beijing, China, by analyzing their concentrations in sediment, 30 d
      exposed caged Chinese rare minnow (Gobiocypris rarus) and triolein embedded
      cellulose acetate membrane (TECAM). The applicability of TECAM to bioavailability
      assessment of PAHs and OCPs for aquatic organisms was also examined. The results
      showed that there were great differences of both bio-sediment accumulation
      factors (BSAFs) and TECAM-sediment accumulation factors (TSAFs) for target
      analytes between experiment sites with variation coefficients of 10%-70% and 20%
      50%, respectively. The BSAFs and TSAFs were independent of relevant Kow. For the
      target pollutants especially PAHs, BSAFs for rare minnow were lower about one
      order of magnitude than those (1-4) predicted by equilibrium partitioning theory
      (EPT). However, TSAFs of PAHs and OCPs for TECAM were almost consistent with the
      EPT. Meanwhile, good correlations were found between the BSAFs and TSAFs for OCPs
      at 5 experiment sites (r = 0.80, 0.87, 0.83, 0.85 and 0.84, p < 0.01), but not
      good for PAHs (p > 0.1). It can be concluded that it is more reliable and
      accurate to assess the pollution status jointly using sediment, fish and TECAM,
      and that TECAM can be used as a biomimetic sampler to predict bioaccumulation
      potential of poorly biodegradable organic compounds like OCPs in fish.

PMID- 19402525
TI  - [Characteristic in electricity-generation and wastewater-treatment by the two
      cylinder microbial fuel cells].
AB  - A two-cylinder MFC, which is of new configuration, was constructed to study its
      power generation and waste water treatment performance. When the graphite granule
      was used in anode as packing material, the internal resistance was 38.9 Omega.
      The anodic resistance, ohmic resistance and the cathodic resistance were 5.1,
      14.1 and 18.7 Omega respectively. The maximal power density was 6,253 mW/m3. When
      the concentration of COD was higher than 1,000 mg/L, the removal load was 1.6
      kg/(m3 x d) and the columbic efficient was 10%-12%. When the graphite granule
      with the diameter of 6 mm, the graphite granule with the diameter of 3 mm, carbon
      felt and the improved carbon felt were used as anode packing materials, the MFCs'
      resistances were 47, 39, 28 and 33 Omega and the stabilization cycles were 20,
      18, 11 and 18 d, respectively. Considering steadily performance, the improved
      carbon felt and the graphite granule with diameter of 3 mm are more suitable as
      anode packing material.

PMID- 19402526
TI  - [Comparison of power generation in microbial fuel cells of two different
      structures].
AB  - Low electricity productivity and high cost are two problems facing the
      development of microbial fuel cell (MFC). Comparative studies on electricity
      generation in MFCs of different designs while under the same conditions are
      important in enhancing the power output. Single-chamber MFC and dual-chamber MFC
      were constructed and acetate was used as the fuel. Power outputs in these MFC
      were compared side by side with a resistance of 1,000 Omega connected to each.
      Experimental results showed that the electricity was generated continuously and
      steadily in the MFCs. The average maximum output voltages obtained by the single
      chamber and dual-chamber MFCs were 600 and 650 mV, respectively. The electric
      cycles were operated for 110 and 90 h for the single-chamber and dual-chamber
      MFCs, respectively. From the single-chamber and dual-chamber MFCs, the maximum
      area power densities were 113.8 and 382.4 mW/m2 respectively, and the maximum
      volumetric power densities were 1.3 and 2.2 mW/m3 respectively. The internal
      resistances of single-chamber and dual-chamber MFC were 188 and 348 Omega,
      respectively. Results indicated that the dual-chamber MFC had a better
      performance than the single-chamber MFC. The effective area of anode and the
      proton exchange membrane had a significant effect on the performance of MFCs.

PMID- 19402527
TI  - [Effect of isomerization of aspartate-7 on the binding of copper (II) ion by the
      beta-amyloid peptide].
AB  - It has been shown for the first time by the method of isothermal calorimetry of
      titration that the N-terminal amino group of the beta-amyloid protein, which
      plays a key role in the binding of copper ion, ceases to form the proper
      coordinating bond as a result of the isomerization of aspartate-7.

PMID- 19402528
TI  - [Effect of fullerenes C60 on the amyloids of X-protein].
AB  - The inhibitory effect of hydrated fullerene C60 (HyFn) and the sodium salt of the
      fullerene polycarboxylic derivative C60Cl (C6H4CH2COONa)5 on the formation of
      amyloid fibrils by X-protein in vitro has been studied by electron microscopy. It
      has been shown that these compounds not only destroyed mature amyloid fibrils but
      also prevented the formation of new fibrils. This property of fullerenes,
      nanoparticles, can be used for the development of a novel medicinal
      nanotechnology in the therapy of amyloidoses.

PMID- 19402529
TI  - [Peculiarities of electrostatic interactions between amino acids and salicylic
      acid in aqueous solution].
AB  - Based on calorimetric data, the enthalpy of the transfer of salicylic acid to
      aqueous buffer solutions with the addition of different amino acids at the
      constant acidity of medium pH 7.35 was determined. It was shown that the
      exothermicity of transfer and negative enthalpic coefficients for these pairwise
      interactions of salicylic acid with amino acids considerably increase with
      increasing charge of amino acid existing in the ionic form under these
      conditions. Weak interactions of salicylic acid with the anionic form of aspartic
      and glutamic acids are related to the repulsion between anion carboxyl groups.
      More intensive interactions are observed for zwitter-ions of glycine and alanine.
      The most intensive specific interactions with salicylic acid are observed for
      lysine and arginine, which exist in the solution as cations.

PMID- 19402530
TI  - [Structural changes in wild-type Cry3A delta-endotoxin and its mutants in ethyl
      alcohol solutions at pH 2-2.5].
AB  - The methods of circular dichroism, scanning microcalorimetry, electron
      microscopy, and proteolysis were used to study the ability of wild-type Cry3A
      delta-endotoxin and three mutant toxins with cysteine substitutions in helices
      alpha3 and alpha4 (domain I) to form oligomeric structures in acidic alcohol
      solutions that reproduce the premembrane environment. At pH 2-2.2 and 20%
      ethanol, the mutant toxins with single substitutions E132C (alpha3) and E160C
      (alpha4), as well as the double mutant E132C/S160C with a cysteine bridge
      connecting helices alpha3 and alpha4, form short linear oligomers specific for
      Cry3A with a high content of the beta-structure and enhanced sensitivity to
      proteolysis with pepsin. The data obtained show that the formation of oligomeric
      structures of this type does not require any divergence of helices alpha3 and
      alpha4 in domain I of the Cry3A toxin. It has been demonstrated that, at higher
      pH values in 20% solution of ethanol, the proteins studied are in a metastable
      state, and their ability to form oligomeric structures depends on temperature.

PMID- 19402532
TI  - [A kinetic model of beta-galactosidase of Escherichia coli].
AB  - On the basis of previously published experimental data, the catalytic cycle of
      Escherichia coli galactosidase has been reconstructed. The enzyme plays a key
      role in the transcription regulation of lac operon. Using the proposed scheme, we
      have built a kinetic model that takes into account the reactions of hydrolysis,
      isomerization as well as galactosylation. Using the experimental data and
      optimization algorithms, all parameters of the model have been estimated. On the
      basis of the model, the features of beta-galactosidase functioning have been
      predicted in a wide range of conditions.

PMID- 19402531
TI  - [Mechanism of manganese transport regulation based on the long RNA helix in
      Brucella].
AB  - It has been found that divalent cation transporters of the Nramp family in cell
      phagosomes and bacteria that parasitize on the cell compete for metals, which is
      crucial for bacterial survival. Long helices were determined by means of our
      algorithm for each mRNA in the 5'-untranslated region in Brucella. Conserved long
      RNA helices were found in mRNA that encode manganese transporters as well as Ni
      dependent Glyoxalase I. We suggest that long helices in these regions are
      involved in the regulation of RNA stability.

PMID- 19402533
TI  - [Effect of low-frequency alternating magnetic fields on the rate of biochemical
      reactions proceeding with the formation of reactive oxygen species].
AB  - It has been shown by an example of the reaction of radical with an oxygen
      molecule that the alternating component of a combined weak magnetic field affects
      the rate constants of chemical reactions. The mechanism of transduction of a weak
      magnetic perturbation from the primary receptor of the field to experimentally
      observed biological effects has been followed. It was found that the external
      magnetic field changes the initial population of energy levels. The magnitude of
      these changes depends on the field parameters. The exposure to an alternating
      field with the proper parameters can substantially increase the concentration of
      reactive oxygen species in biological systems. By controlling their concentration
      by means of weak magnetic field, it is possible to affect the key components of
      metabolism.

PMID- 19402534
TI  - [The action of week inorganic acids and lower carboxylic acids on the
      conductivity of bilayer lipid membranes].
AB  - The ability of weak inorganic acids (H2S, HCN) and lower carboxylic acids to
      interact with bilayer lipid membranes, change their conductivity, and act as
      protonophores has been investigated. The mechanism of changes in BLM conductivity
      was studied. Factors influencing the interaction of acids with model lipid
      membranes were determined. Maximum changes in conductivity were observed at pH
      values equal to the dissociation constants of weak acids and depend on the
      coefficients of distribution "octanol-water".

PMID- 19402535
TI  - [Effect of dithiothreitol on the deformation and La(3+)-induced fusion of human
      erythrocytes].
AB  - The effect of dithiothreitol on the deformation and La(3+)-induced fusion of
      human erythrocytes was studied. It was shown that dithiothreitol did not affect
      the deformation of erythrocytes. At the same time, dithiothreitol practically
      completely inhibited the fusion of erythrocytes.

PMID- 19402536
TI  - [Expression of CD3 complexes by native and UV-irradiated T lymphocytes of human
      blood after modification by a preparation of leucocytic alpha-interferon].
AB  - The influence of leucocytic alpha-interferon in concentrations of 0.01, 0.1, 1,
      10, and 100 IU/ml on the expression of CD3 complexes by native and photomodified
      T lymphocytes of human blood has been studied. It was found that the irradiation
      of suspensions of T cells by UV-light in doses of 151-906 J/m2 increases, and in
      a dose of 1359 J/m2, reduces the quantity of CD3 complexes on the surface of
      their membranes. It was shown that the injection of cytokine in concentrations of
      0.01-100 IU/ml into a suspension of irradiated T lymphocytes levels off the
      immunosuppressive action of maximal doses of UV-radiation (1359 J/m2), inducing
      the recovery and increase in their antigen-recognizing capacity. The data on the
      antigen-recognizing capacity of UV-irradiated T lymphocytes of human blood,
      modified by alpha-interferon, enable one to predict the results of seances of
      autotransfusion of UV-irradiated blood in the case of combined use of UV
      irradiation of blood and cytokinotherapy.

PMID- 19402537
TI  - [The role of protein kinase SAPK/JNK in cell responses to low-intensity
      nonionizing radiation].
AB  - The effect of low-intensity lases light (0.2 mW/cm2, 632.8 nm, exposure time 1
      min) or centimeter waves (8.15-18 GHz, 1 W/cm2, exposure time 1 h) on
      PhosphoSAPK/JNK production in mice lymphocytes was investigated. Normal isolated
      spleen lymphocytes or cells incubated previously with geldanamycin, an inhibitor
      of heat shock protein 90 (HSP90), were used in the experiments. A significant
      stimulation of PhosphoSAPK/JNK production in lymphocytes after treatment with
      laser light or microwaves has been shown in both cell models. It was proposed
      that the activation of SAPK/JNK signal pathway plays one of the central roles in
      cellular stress response to low-power nonionizing radiation.

PMID- 19402538
TI  - [Immunomodulatory effects of thymopentin under acute and chronic inflammations in
      mice].
AB  - The effects of thymopentin, a synthetic analogue of the active center of the
      thymus hormone thymopoietin, on the immune status of mice with two different
      models of inflammation induced by injection of lipopolysaccaride (LPS) from gram
      negative bacteria were studied. Acute inflammation was induced by a single
      injection of LPS in a dose of 250 microg/100 g of body weight, and chronic
      inflammation (sepsis) was modeled by a daily injection of LPS for 11 days with a
      gradual increase in the dose range from 25 to 250 microg/100 g of body weight.
      Under acute inflammation, a preliminary injection of thymopentin did not induce
      any additional stimulation in cytokine production increased by LPS. On the
      contrary, whereas the chronic introduction of LPS was characterized by a
      depressed production of several cytokines, thymopentin produced an
      immunostimulating effect. Thus, an increase in the production of nitric oxide,
      interferon-gamma, and Hsp70 was demonstrated. In addition, a more effective
      restoration of the number of thymus cells, as well as an increase in macrophage
      tumor necrosis factor-alpha production were observed after repeal of LPS +
      hormone injections. The results show that preliminary application of thymopentin
      promotes the regulation of immune cell activity under acute and chronic
      inflammation.

PMID- 19402540
TI  - [About the formation of an image in the inverted retina of the eye].
AB  - Possible distortions of images of an object by the layer of nerve cells have been
      analyzed. It has been shown that, based on microoscillations of the visual
      apparatus, it is possible to propose the procedures of processing the arising
      diffraction scattering spectra and isolating from these spectra initial images
      that do not contradict the available morphological and neurophysiological data.

PMID- 19402539
TI  - [Mathematical modeling of the response of a resistive vessel to pressure].
AB  - The response of small arterial vessels to internal pressure makes an essential
      contribution to autoregulation in the vascular bed. It is believed that
      intracellular cytosolic Ca2+ concentration plays a pivotal role in the regulation
      of smooth muscle contractility and hence of vascular lumen. A simple mathematical
      model of blood flow in a resistive vessel is suggested. The model is based on the
      experimental data obtained for cerebral arteries, but may be used for any other
      resistive vessel. The model not only describes the regulation of the vascular
      lumer by transmural pressure but also shows realistic behaviour of the radius and
      intracellular cytosolic Ca2+ concentration at different velocities of pressure
      change. Possible variations of the radius along the vessel as a consequence of
      the Bayliss effect are considered.

PMID- 19402541
TI  - [Memory blocking: facts, problems, and models].
AB  - The tip-of-the-tongue state, or memory blocking, has been investigated from the
      point of view of possibilities of its neural network modeling. The results of
      neuropsychological and neurobiological studies on memory blocking have been
      reviewed, and basic problems whose solution could contribute to the comprehension
      of this phenomenon have been formulated. One of such questions is the existence
      of a paradoxical discrepancy between the subjective assurance that a pattern is
      familiar and the impossibility to recollect it fully. To explain this
      discrepancy, we propose a biologically plausible neural network model of
      recognition demonstrating a radical superiority of the capacity for the
      recognition of a pattern as compared with its recollection.

PMID- 19402542
TI  - [Locomotion induced by epidural stimulation in decerebrate cat after spinal cord
      injury].
AB  - The effect of partial and complete spinal cord injury (Th7-Th8) on locomotor
      activity evoked by epidural electrical stimulation (L5 segment, stimulation
      frequency 5 Hz, current strength 80-100 microA) in decerebrate cats has been
      investigated. It was established that the cutting of dorsal columns did not
      influence substantially the locomotion. The destruction of the ventral spinal
      quadrant resulted in the deterioration and instability of the locomotor rhythm.
      The injury of lateral or medial descending motor systems led to a redistribution
      of the tone in antagonist muscles. It was found that locomotion can be evoked by
      epidural stimulation within 20 h after the complete transaction of the spinal
      cord. The restoration of polysynaptic components in EMG responses correlated with
      the restoration of the stepping function. The data obtained confirm that the
      initiation of locomotion under epidural stimulation is caused by direct action on
      intraspinal systems responsible for locomotion regulation. In the case of intact
      or partially injured spinal cord, this effect is under the influence of
      supraspinal motor systems correcting and stabilizing the evoked locomotor
      pattern.

PMID- 19402543
TI  - [Peculiarities of the locomotion of the Chilopoda Scolopendra cingulata upon
      changes in speed].
AB  - The spatial and temporal parameters of movements of scolopendra legs after
      instantaneous changes in speed from V1 to V2 double dagger V2 were investigated.
      It was shown that: (1) the synergy of the walking mode "footprint into footprint"
      is kept as the locomotion speed changes; (2) the continuity of metachronal waves
      is not disturbed as V changes; 3) the set of all scolopendra legs within some
      time after the change in V is subdivided into two groups: (a) a group of fore
      legs that create a "new" trackway of steps with pace l2 and (b) a group of hind
      legs that continue following the previous trackway of steps with pace l1. The
      legs of group (a) walk in the stationary mode corresponding to speed V2, whilst
      the legs of group (b), in a transient changing mode. The values of walking
      parameters in groups (a) and (b) differ. Gradually, with a speed of metachronal
      waves, group (a) reorganizes the function of legs of group (b) from the transient
      changing to the stationary mode.

PMID- 19402544
TI  - [The use of EPR spectroscopy to control the changes in organism radioresistance.
      Experimental results].
AB  - The responses of deoxyribonucleotide (dNTP), DNA, and protein synthesis systems
      in blood-forming organs of animals (dogs, mice) as well as changes in Fe(3+)
      transferrin (Fe(3+)-TF) and Cu(2+)-ceruloplasmin (Cu(2+)-CP) pools in blood to
      gamma-irradiation and the administration of radioprotectors have been studied. It
      has been shown that changes in Fe(3+)-TF and Cu(2+)-CP pools in blood are indices
      of changes of body radioresistance and are reliably controlled by the EPR
      technique. An increase in the Fe(3+)-TF pool promotes the activation of synthesis
      of dNTP, DNA, and Fe(3+)-containing proteins, which are essential for repair
      efficiency during early post-irradiation time as well as for the development of
      compensatory and restorative reactions of cellular systems; i.e., they are
      responsible for body resistance to DNA-damaging factors. It is important that the
      intensity of responses depends on the initial state of the organism. Thus, dogs
      with initial individual characteristics of blood typical for "suppressed" or
      "activated" states had abnormally high responses to irradiation by low doses of
      0.25 and 0.5 Gy. This fact is important for the estimation of consequences of
      prolonged low-dose irradiation for human population. It has been shown that
      radioprotectors, efficient in survival test activate the synthesis of dNTP, DNA,
      and proteins in organs. The intensity of dNTP synthesis and the time when dNTP
      pools get maximum values determine the efficiency of protectors and the time of
      irradiation after their administration.

PMID- 19402545
TI  - [The use of EPR spectroscopy to control the changes in organism radioresistance.
      Clinical results].
AB  - It has been shown that changes in Fe(3+)-transferrin and Cu(2+)-ceruloplasmin
      pools, which are trust-worthy controlled by the EPR technique in whole blood,
      blood plasma, and serum, as well as changes in the extracellular DNA content in
      blood plasma are markers of changes in organism radioresistance. This has been
      proved during the medical examination of the Chernobyl accident recovery workers
      and civil population, including children, exposed to low-intensity radiation, as
      well as during clinical investigation of new radioprotectors.

PMID- 19402546
TI  - [Autowaves in a model of growth of an invasive tumor].
AB  - A mathematical model for the invasive tumour growth has been constructed, which
      takes cell division, death, and motility into account. The model includes local
      cell density and the distribution of nutrient (oxygen) concentration. Cancer
      cells die in the absence of nutrients; therefore, the distribution of oxygen in
      tissue substantially affects both the tumour proliferation rate and structure.
      The model adequately describes the experimentally measured rate of tumour
      proliferation. The existence of autowave solutions has been demonstrated, and
      their properties have been investigated. The results are compared with the
      properties of the Kolmogorov-Petrovskii-Piskunov and Fisher equations. It is
      shown that the nutrient distribution influences the speed selection and the
      convergence of the initial conditions to the automodel solution.

PMID- 19402547
TI  - [Physical methods and molecular biology].
AB  - The review is devoted to the description of the current state of physical and
      chemical methods used for studying the structural and functional bases of living
      processes. Special attention is focused on the physical methods that have opened
      a new page in the research of the structure of biological macromolecules. They
      include primarily the methods of detecting and manipulating single molecules
      using optical and magnetic traps. New physical methods, such as two-dimensional
      infrared spectroscopy, fluorescence correlation spectroscopy and magnetic
      resonance microscopy are also analyzed briefly in the review. The path that
      physics and biology have passed for the latest 55 years shows that there is no
      single method providing all necessary information on macromolecules and their
      interactions. Each method provides its space-time view of the system. All
      physical methods are complementary. It is just complementarity that is the
      fundamental idea justifying the existence in practice of all physical methods,
      whose description is the aim of the review.

PMID- 19402548
TI  - [Functional organization of working memory in seven- to eight-year-old children].

PMID- 19402549
TI  - [EEG markers of the stability training effect during the rehabilitation of
      patients with posttraumatic Korsakoffs syndrome].

PMID- 19402550
TI  - [Unconscious context control of visual perception of simple stimuli: a study
      using evoked potentials].

PMID- 19402551
TI  - [Regulation of the head's position in the normal state and left- and right-sided
      forms of cervical dystonia].

PMID- 19402552
TI  - [The respiratory function of blood in elderly and old age and the factors that
      determine it].

PMID- 19402553
TI  - [Reaction to the perturbation of the vertical posture under various conditions of
      standing and in the case of additional support].

PMID- 19402554
TI  - [Human upright posture control in a virtual visual environment].

PMID- 19402555
TI  - [Blood flow oscillations at a frequency of about 0.1 Hz in skin microvessels do
      not reflect the parasympathetic regulation of their tone].

PMID- 19402556
TI  - [The effect of the background color of computer programs on the functional state
      of preschool children working with a computer].

PMID- 19402557
TI  - [Energy supply for muscular activity of five- to six-year-old children and
      complex assessment of physical working capacity].

PMID- 19402558
TI  - [Gastric secretion in 7-32-year-old wrestlers].

PMID- 19402559
TI  - [Exogenous and endogenous factors influence the internal synchronization of the
      daily rhythms of autonomic functions in humans under normal and subextreme
      environmental conditions].

PMID- 19402560
TI  - [Human respiratory muscles: three levels of control].

PMID- 19402561
TI  - [Heart rate control: f-channel blockers].

PMID- 19402562
TI  - [Comparative efficiencies of different methods for removing blink artifacts in
      analyzing quantitative electroencephalogram and event-related potentials].

PMID- 19402563
TI  - [Visual perception as an integral characteristic of the psychophysiological
      development of 6-7-year-old children].

PMID- 19402564
TI  - [Monitoring the functional state of human operators by the fundamental tone and
      spectrum of speech parameters].

PMID- 19402565
TI  - [Recognition of masked significant and insignificant images of household items].

PMID- 19402566
TI  - Stroke and age-brain barrier: how many bricks in the wall?
AB  - Although older people contribute more and more to the increasing social burden of
      stroke, they are often excluded from potentially effective treatments in clinical
      practice. With the aim to separate myth from reality, we have examined the
      barriers preventing such therapies (with reference to atrial fibrillation,
      thrombolysis, carotid stenosis and patent foramen ovale) in the elderly. We
      conclude that elevated age alone should not be considered an exclusion criterion
      and both stroke physicians and researchers should make efforts to greatly improve
      management of these patients.

PMID- 19402567
TI  - Diagnostic and therapeutic trajectory of cluster headache patients in Flanders.
AB  - OBJECTIVE: A fraction of cluster headache (CH) patients face diagnostic delay,
      misdiagnosis, undertreatment and mismanagement. Specific data for Flanders are
      warranted. METHODS: Data on CH characteristics, diagnostic process and treatment
      history were gathered using a self-administered questionnaire with 90 items in CH
      patients that presented to 4 neurology outpatient clinics. RESULTS: Data for 85
      patients (77 men) with a mean age of 44 years (range 23-69) were analysed. 79%
      suffered from episodic CH and 21% from chronic CH. A mean diagnostic delay of 44
      months was reported. 31% of patients had to wait more than 4 years for the CH
      diagnosis. 52% of patients consulted at least 3 physicians prior to CH diagnosis.
      Most common misdiagnoses were migraine (45%), sinusitis (23%), tooth/jaw problems
      (23%), tension-type headache (16%) and trigeminal neuralgia (16%). A significant
      percentage of patients had never received access to injectable sumatriptan (26%)
      or oxygen (31%). Most prescribed preventative drugs after the CH diagnosis were
      verapamil (82%), lithium (35%), methysergide (31%) and topiramate (22%). Despite
      the CH diagnosis, ineffective preventatives were still used in some, including
      propranolol (12%), amitriptyline (9%) and carbamazepine (12%). 31% of patients
      had undergone invasive therapy prior to CH diagnosis, including dental procedures
      (21%) and sinus surgery (10%). CONCLUSION: Despite the obvious methodological
      limitations of this study, the need for better medical education on CH is evident
      to optimize CH management in Flanders.

PMID- 19402568
TI  - Relationship between admission pulse pressure and clinical outcome during
      hospitalization among acute stroke patients.
AB  - BACKGROUND AND PURPOSE: There are currently no data on the relationship between
      admission pulse pressure (PP) level and short term clinical outcome among acute
      stroke patients in the Chinese population. We studied the association between
      admission PP and in-hospital death or dependency among acute stroke patients in
      Inner Mongolia, China. METHODS: A total of 2,178 acute ischemic stroke, 1,604
      intracerebral hemorrhage and 156 subarachnoid hemorrhage patients were included
      in the present study. Blood pressure and other study variables were collected
      within the first 24-hours of admission. Study outcome (death or dependency) was
      evaluated by trained neurologists during hospitalization. The associations
      between admission PP and study outcome were analyzed by using multiple logistic
      model. RESULTS: PP at admission was not significantly associated with study
      outcome in acute ischemic stroke and subarachnoid hemorrhage. On the other hand,
      PP was significantly and positively associated with odds of study outcome in
      acute intracerebral hemorrhage. Compared to those with PP < 50 mmHg, multivariate
      adjusted odds ratio (95% confidence interval) of study outcome was 1.545 (1.111
      2.148) among intracerebral hemorrhage patients with PP > or = 70 mmHg (p = 0.01).
      CONCLUSION: Increased PP was significantly and positively associated with poor
      clinical outcome among patients with acute intracerebral hemorrhage, but not
      acute ischemic stroke and subarachnoid hemorrhage, in Inner Mongolia, China.

PMID- 19402569
TI  - Behavioral and neurochemical profile of m-CPP following exposure to single
      restraint stress in rat.
AB  - The present study was designed to monitor the responsiveness of 5
      hydroxytryptamine (5-HT; serotonin)-2C receptors following the exposure to
      restraint stress in rats. Rats were restrained for 2 hours. 24-h after the
      termination of the restraint period, 1-(m-Chlorophenyl)piperazine (m-CPP; a 5-HT
      2C agonist) at the doses of 1.5 mg/kg or 3.0 mg/kg and saline (1 ml/kg), was
      injected to unrestrained and restrained animals. Hypolocomotive effects (home
      cage activity, open field activity and motor coordination) and anxiogenic-like
      effects (light-dark activity and plus maze activity) were successively monitored
      in each animal after the drug or saline administration. Rats were decapitated 1-h
      post-injection to collect brain samples for neurochemical estimation by HPLC-EC.
      Our results show that differences in the hypolocomotive and anxiogenic-like
      effects of m-CPP between restrained and unrestrained animals could not be
      demonstrated in the present experimental paradigm. This was due to the fact that
      the behavioral effects were already marked after restraint leaving little room
      for an additional m-CPP effect. The effects of m-CPP on increasing 5
      hydroxyindole acetic acid (5-HIAA) and decreasing dihydroxy phenyl acetic acid
      (DOPAC) levels were more pronounced (p < 0.01) in restrained than unrestrained
      animals. The results suggest that behavioral responses to m-CPP and stress are
      similar The attenuation of m-CPP changes in 5-HIAA and DOPAC levels may be due to
      a decreased responsiveness of 5-HT-2C receptors in restrained animals.

PMID- 19402570
TI  - Genistein, a soybean isoflavone, reduces the production of pro-inflammatory and
      adhesion molecules induced by hemolysate in brain microvascular endothelial
      cells.
AB  - Genistein (4',5,7-trihydroxyisoflavone) is the most abundant isoflavone found in
      the soybean that exhibits an anti-inflammatory effect. The present study was
      designed to examine the effects of genistein on expression levels of hemolysate
      induced proinflammatory and adhesion molecules in SD rat brain microvascular
      endothelial cells (BMECs). Genistein treatment attenuated hemolysate-induced
      nuclear factor-kappa B (NF-kappaB) p65 translocation in BMECs. In addition,
      genistein suppressed the expression levels of tumor necrosis factor-alpha (TNF
      alpha), monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion
      molecule-1 (ICAM-1), but not vascular cell adhesion molecule-1 (VCAM-1). The
      inhibitory rate of 50 pM genistein for TNF-alpha, MCP-1 and ICAM-1 was 65.4%,
      60.5% and 54.9% respectively. These inhibitory effects of genistein on
      proinflammatory and adhesion molecules were not due to decreased BMEC viability
      as assessed by MTT test. Taken together the present study suggests that genistein
      suppresses expression levels of hemolysate-induced pro-inflammatory and adhesion
      molecules in cerebral endothelial cells.

PMID- 19402571
TI  - Cerebral oedema in episodic ataxia.
AB  - We report a patient with episodic ataxia (presumably of type 2) who developed
      cerebral oedema secondary to a common infection (presumably viral). Cerebral
      oedema may be a part of the clinical spectrum of familial episodic ataxia and
      argues for an overlap with hemiplegic migraine. It is suggested to consider a
      diagnosis of episodic ataxia or familial hemiplegic migraine in catastrophic
      reactions to apparent trivial trauma or infection.

PMID- 19402572
TI  - An unusual case of 4-aminopyridine toxicity in a multiple sclerosis patient:
      epileptic disorder or toxic encephalopathy?
AB  - We report the case of a 45-year old female multiple sclerosis patient, who
      accidentally was overdosed with 4-aminopyridine which resulted in dystonic,
      choreathetoid type abnormal movements in the four limbs, motoric distress,
      confusion and opisthotonus. There is little known about 4-aminopyridine toxicity.
      There are only a few reported cases ranging from mild paresthesias to tonic
      clonic seizures. 4-aminopyridine enhances neuronal conduction at neuromuscular
      synapses and is indicated in the treatment of selected neurological disorders
      including multiple sclerosis (MS) and myasthenia gravis, among others.

PMID- 19402573
TI  - Charles Bonnet syndrome disappearing with carbamazepine and valproic acid but not
      with levetiracetam.
AB  - Although Charles Bonnet syndrome (CBS) appears to be more frequent than
      historically reported, there are very few reports about possible pharmacological
      treatments. We report the case of a CBS disappearing completely with successive
      monotherapies of carbamazepine and valproic acid but worsening with
      levetiracetam.

PMID- 19402574
TI  - Cerebral vasculitis mimicking migraine with aura in a patient with Crohn's
      disease.
AB  - INTRODUCTION: Whereas extraintestinal manifestations of inflammatory bowel
      disease in general are quite common, cerebral vasculitis is considered a very
      rare condition. We present a case of Crohn's disease-associated vasculitis
      mimicking migraine with aura. CASE DESCRIPTION: A 28-year-old woman with Crohn's
      disease and known migraine with aura had suffered from daily migraine attacks
      with recurrent focal neurological deficits for 6 weeks. Cerebral magnetic
      resonance imaging showed multiple acute, subacute, and chronic ischemic lesions
      in different vascular territories. Magnetic resonance and computed tomography
      angiography demonstrated vessel changes consistent with cerebral vasculitis.
      Laboratory investigations revealed systemic inflammation and lymphomonocytic
      pleocytosis of cerebrospinal fluid, supporting the diagnosis of Crohn's disease
      associated vasculitis. Symptoms and inflammatory parameters quickly normalized
      after high-dose prednisolone treatment. During immunosuppressive therapy,
      migraine recurred only once in 11 months. DISCUSSION: Cerebral vasculitis is a
      very rare but severe complication in Crohn's disease and should be excluded in
      case of comorbidity with migraine with aura. In our patient, migraine with aura
      may have been the only symptom of cerebral vasculitis for several years.

PMID- 19402575
TI  - Joubert syndrome associated with new MRI findings and posterior reversible
      encephalopathy syndrome.
AB  - Joubert syndrome (JS) is an inherited disorder characterized by transient
      episodic hyperpnea, ataxia, and vermian hypoplasia. Typical imaging findings of
      JS include hypoplasia or aplasia of the cerebellar vermis, thick and elongated
      superior cerebellarpeduncles and an abnormally deep interpeduncular fossa with
      'molar tooth sign'. We present a case of JS associated with deep cerebral sulci
      and fissures, polymicrogyria, and additional findings of posterior reversible
      encephalopathy syndrome associated with renal involvement.

PMID- 19402576
TI  - Megalencephalic leukoencephalopathy with subcortical cysts in an adult.

PMID- 19402577
TI  - Incidental hemangioblastoma of the filum terminale.
AB  - Filum terminale hemangioblastoma is an extremely rare tumour with only a few case
      reports in the literature. The natural history is unknown but benign as well as
      more aggressive presentations have been reported. The authors present the first
      such lesion discovered incidentally and discuss the available literature.

PMID- 19402578
TI  - Extensor plantar response elicited by passive head flexion.

PMID- 19402579
TI  - Supracondylar femur fracture complicating epileptic insult: a specific and under
      diagnosed complication?

PMID- 19402580
TI  - Risk factors for anaemia in schoolchildren in Tanga Region, Tanzania.
AB  - Anaemia is one of the major public health problems affecting more than half of
      school children along the coast in Tanzania. Due to the multiplicity of its
      causes it sometimes becomes difficult to find appropriate intervention measures.
      In order to assist schools in implementing appropriate public health measures for
      anaemia in Tanga Region of Tanzania risk factors were investigated in school
      children. A total of 845 schoolchildren age 7-14 years were randomly selected in
      a cross-sectional survey conducted in 20 randomly selected schools for inclusion
      in the investigations. Socio-economic, environmental and biological data were
      collected, as well as academic information, health care and feeding practices.
      Diagnosis of anaemia was based on haemoglobin concentration below 115 g/L
      determined by HemoCue meter. Serum Retinol was determined by High performance
      liquid chromatography and serum ferritin by an Enzyme linked immunosorbent assay.
      Urine from each child was tested for blood using a haematest reagent strip and
      those testing positive were examined microscopically by filtration method for
      Schistosoma haematobium ova. A faecal sample collected from them was also
      examined microscopically for ova and larvae of intestinal worms. To analyse
      variables associated with anaemia a stepwise multiple regression model was used.
      The prevalence of anaemia was 79.6%. Micronutrient deficiencies were highly
      prevalent. Iron deficiency (SF <20 microg/dl) was affecting 33%, vitamin A
      deficiency (SR < 20 microg/dL) 31.9% and 25% of the children had mild iodine
      deficiency (UIE < 20 microg/L). Intestinal helminths were also highly prevalent;
      68% of children had hookworm and 54% had urinary schistosomiasis. Inadequate diet
      was a feature in >50% of children. About 10% of households had no latrines and
      multiple infection rank score was high especially in older age children. The risk
      of having anaemia was two times higher in children with iron deficiency (RR=2.1)
      and 49% higher in those with vitamin A deficiency. These deficiencies correlated
      significantly with the anaemia (P<0.05). Vitamin A deficiency and infections with
      hookworm and schistosomiasis were the most significant factors predicting for
      anaemia (r=0.318 and r2=0.101). We therefore conclude that high prevalence of
      infections and nutritional deficiencies are important risk factors for anaemia in
      this community. The high attributable fractions for hookworm, schistosomiasis,
      iron deficiency and vitamin A confirms that these are significant risk factors to
      be considered when designing public health measures for anaemia prevention in
      this community.

PMID- 19402581
TI  - Attitudes and perceived impact of antiretroviral therapy on sexual risk behaviour
      among young people in Kahe, Moshi Rural District, Tanzania.
AB  - Free antiretroviral therapy (ART) has been provided through the public health
      system in Tanzania since 2004. The success of national ART roll out programme is
      premised upon collaborative efforts of health systems, communities and policy
      environment. However, community perceptions of ART and its implications on sexual
      behaviours and HIV/AIDS prevention remain largely unknown. Drawing on focus group
      discussions with young people, this paper examines perception about ART and the
      potential impact of antiretroviral therapy on risk sexual behaviour in rural
      Tanzania. Participants included a purposively selected sample of males and
      females aged 14-24 years. Results show that young people were both optimistic and
      concerned regarding availability of ART. Positive attitudes toward ART were
      associated with public health significance of therapy in managing opportunistic
      infections and extending lives of HIV infected persons. However, the positive
      outcomes of therapy were considered to be short lived, unsustainable and
      potentially threatening to the sexual health and wellbeing of HIV negative
      members in the community. ART was considered to empower infected persons to
      intentionally spread HIV to uninfected individuals in the community through
      deliberate unprotected sexual activities. The study highlights the significance
      of reinforcing HIV prevention while underscoring the need to provide appropriate
      information and increasing access to ART in rural areas of Tanzania. In
      conclusion, creating a therapy friendly atmosphere through information delivery
      is crucial in promoting social acceptability of antiretroviral therapy among
      youths. Efforts to improve access to antiretroviral drugs should re-emphasize
      prevention counselling to minimize sexual transmission of HIV.

PMID- 19402582
TI  - Community knowledge, attitude and practice towards sexually transmitted diseases
      and HIV infection in Biharamulo and Muleba districts in Kagera Region, Tanzania.
AB  - The study was conducted to determine knowledge, attitude and practice towards
      Sexually Transmitted Diseases and HIV infections among communities in Biharamulo
      and Muleba districts, Kagera Tanzania. A total of 915 study participants were
      recruited and most of them (96.3%) knew that there are diseases which could be
      transmitted through sexual contact. Seventy one percent of participants thought
      STDs could be acquired through sharing a towel while fifty percent thought HIV
      could be transmitted through insect bites. Eighty five percent of school pupils
      who participated in the study reported to have been taught about AIDS and less
      than 30% on sex and pregnancy. Sixty three percent of study participants were of
      the opinion that a girl or woman should not refuse to have sex after being given
      a gift, and having sex with an elder partner was thought to be acceptable by
      almost fifty percent of participants. Over 50% percent of interviewees thought a
      girl or woman should not refuse to have sex with their friends. Although 99% of
      interviewees reported to have ever heard about condoms, only 28% reported to have
      ever used them irrespective of been affordable. Most schoolboys and about 50% of
      schoolgirls reported to have experienced sex by the time of the study. Thirty
      eight percent of girls reported to have first sex at the age of 14 years. Nine
      percent of the participants who reported to have experienced sex were forced to
      do so. Knowledge regarding STDs and HIV/AIDS was high among participants, but a
      sizeable proportion report misconception on transmission of STDs/HIV such as
      through sharing a towel and insect bites. Therefore it is recommended that S&RH
      intervention programme should address these misconceptions in order to match
      knowledge and practice, and achieve the intended objectives.

PMID- 19402583
TI  - Manifestations and reduction strategies of stigma and discrimination on people
      living with HIV/AIDS in Tanzania.
AB  - HIV/AIDS-related stigma, and its associated discrimination, is known to
      negatively affect all aspects of HIV prevention, care and treatment. Studies have
      revealed the extent to which individuals are stigmatized and discriminated
      against the health care system. However, there has been limited information on
      stigma manifestations and reduction interventions. The main objective of the
      study was to determine the magnitude and factors influencing HIV/AIDS-related
      stigma and discrimination with a specific focus on the manifestations and
      reduction interventions. In-depth interviews, exit interviews and focus group
      discussions were deployed in the study. Results have shown that HIV/AIDS is
      increasingly conceptualized as a continuum between prevention and care, effects
      of stigma and discrimination are from both health facilities and communities.
      While religious leaders isolate people living with HIV/AIDS (PLWHAs) and consider
      them as most promiscuous, health workers also have strong negative attitudes and
      feelings and as a result PLWHAs refrain from counselling and testing services. A
      stigmatizing social environment was found to pose barriers to all strategies
      and/or interventions that are aimed at reducing this situation. Because of stigma
      and discrimination, people living with HIV/AIDS receive inadequate treatment, as
      such they decline to divulge their status to partners or change their behaviour
      avoiding depressing reactions. Basing on that therefore, adequate outreach
      services at both community and health facility levels be established and line up
      in the fight against stigma and discrimination facing people living with
      HIV/AIDS.

PMID- 19402584
TI  - Knowledge and practices on malaria treatment measures among pregnant women in
      Abeokuta, Nigeria.
AB  - The knowledge and practices on malaria treatment measures were assessed among
      1400 pregnant women in semi-urban and rural communities (Akomoje, Iberekodo,
      Osiele and Sabopapamaru) of Abeokuta, Nigeria in 2006. Data was collected using
      structured questionnaires and focus group discussions. The largest proportion
      (41%) of the respondents was in the age group 21-25years. About three quarters
      (74%) of the women were multigravids. Sixty-five percent of the women had between
      three to four episodes of malaria per year. According to the respondents,
      symptoms associated with malaria in pregnancy included abdominal pains and foetal
      weakness due to reduced kicks (53%), body pains and headaches (27%) and anaemia
      (20%). Sixty-eight percent of the pregnant women utilized herbs for treating
      symptoms associated with malaria due to its effectiveness and suitability and not
      due to financial constraint or lack of access to health facility. Though most
      women utilized herbs, 32% relied more on the use of antimalarials. Sulfadoxine
      pyrimethamine was the preferred antimalarial during pregnancy at the 2nd and 3rd
      trimesters. Only 15% of the women were using insecticide treated mosquito nets
      for personal protection. The majority (77%) of respondents used nylon net to
      screen their windows off mosquitoes. Since malaria poses adverse effect on the
      mother and developing foetus, health education becomes very essential to the
      traditional birth attendants and the women who patronize them. Pregnant women who
      attend traditional birth homes should be encouraged to also attend orthodox
      antenatal clinics, in order to receive proper and adequate treatment against
      malaria for themselves and the foetus.

PMID- 19402585
TI  - Community directed interventions for malaria, tuberculosis and vitamin A in
      onchocerciasis endemic districts of Tanzania.
AB  - In recognising the success attained through community-directed treatment with
      Ivermectin, there has been a growing interest to use a similar approach for
      delivery of interventions against other communicable diseases. This study was
      conducted in 2007 to evaluate the impact of community directed intervention (CDI)
      on delivering five health interventions namely Vitamin A supplementation (VAS),
      community-directed treatment with Ivermectin (CDTi), distribution of insecticide
      treated nets (ITN), directly observed treatment of tuberculosis (DOTS), and home
      based management of malaria (HMM). The study was carried out in onchocerciasis
      endemic districts of Kilosa, Muheza, Lushoto, Korogwe and Ulanga districts in
      Tanzania. A total of 250 households were involved in the study for the period of
      two years. During the first year, one new intervention was added in each study
      district. A second new intervention was then added in the same manner during the
      second study year. In the control district all interventions, with the exception
      of Ivermectin distribution, continued to be delivered in the traditional manner
      throughout the study period. Results showed that Ivermectin treatment coverage in
      the CDI districts (88%) was significantly (P<0.005) higher than in the control
      district (77%). The coverage of VAS was 84 +/- 7%, showing very little difference
      between control and intervention districts (P>0.05). The DOTS treatment
      completion rate was observed only in Korogwe where 4 out 7 patients had completed
      their treatment. The proportions of pregnant women and <5 years children sleeping
      under ITN in the CDI districts (range: 83-100%) were significantly higher (P<
      0.05) than those in the control district (40-43%). There was also a higher
      proportion of malaria cases referred in the intervention districts (42%) than in
      the control district (21%) (P<0.005). Likewise, the proportion of <5 years
      children who were presumptively diagnosed with malaria and received appropriated
      treatment within 24 hours in the intervention districts (17-29%) was higher than
      those in the control district (4%) (P<0.005). The costs incurred per integrated
      programme in the intervention districts were much lower than those in the control
      district. In conclusion, our results showed higher coverage of interventions in
      the CDI districts without necessarily increasing the cost.

PMID- 19402586
TI  - Knowledge, attitudes, and self care practices associated with glaucoma among
      hospital workers in Ile-Ife, Osun State, Nigeria.
AB  - This study was carried out to determine the level of correct knowledge about
      glaucoma and attitudes towards blindness prevention and treatment, and how these
      factors influence self care practices among teaching hospital workers. A random
      sample of the workers at Obafemi Awolowo University Teaching Hospital in Nigeria
      was interviewed. All respondents were asked the year of their last visit within
      the past one year to an eye care practitioner. A total of 205 members of staff
      were interviewed; 85 (41.5%) were males and 120 (58.5%) females. Female sex
      (P=0.003), medical profession (P=0.007), ophthalmic specialty (P=0.0001),
      secondary or tertiary education (P=0.001), and recent visit to an eye
      practitioner (P=0.012) were significant predictors of knowledge of glaucoma as a
      blinding disease. Younger people believed blindness prevention and treatment were
      the highest priorities compared with other diseases. Those who work in the
      ophthalmic unit and those who had relatives who had been blind from glaucoma also
      considered blindness treatment to be the highest priority compared with other
      diseases. People with a relative that had previous diagnosis of glaucoma
      (P=0.0001), older people (P=0.003), females (P=0.001), and people with correct
      knowledge of common eye diseases (P=0.0005) were significantly more likely to be
      under eye care. No interaction was found between knowledge and positive attitudes
      to self care practices. In conclusion, this study shows that there is a gap in
      the knowledge and understanding of glaucoma among Nigerian hospital workers,
      especially among the non-medical staff. There is therefore a need for eye health
      promotion activities targeting all workers at primary healthcare facilities.

PMID- 19402587
TI  - Modes of delivery assistance in Bangladesh.
AB  - In Bangladesh, like many other developing countries among the major underlying
      factors leading to poor maternal situation include very low percentages of women
      actually seek professional medical assistance for pregnancy related care,
      deliveries and complications. This paper employs statistical methods to identify
      the factors associated with modes of delivery assistance in Bangladesh. To reach
      our goal Bangladesh Demographic and Health Survey of 2004 data for last five
      years (N = 4873) was used. Descriptive and multivariate logistic regression
      methods were employed in analyzing the data. It was observed that almost all the
      deliveries (88.8%) took place at the homes of the women and most of them (85.6%)
      were assisted by untrained traditional birth attendants, relatives or neighbours
      in unsafe and unhygienic conditions. Only 14.4% of the deliveries were assisted
      by the medically trained persons such as registered physicians, nurses or
      paramedics. The rate of receiving assistance from medically trained personnel was
      lower among mothers utilizing insufficient antenatal health care services. Middle
      aged women received delivery assistance more from medically trained personnel
      than the adolescents and women with higher age group. Multivariate logistic
      regression analysis shows that higher educated women were two-and-a-half times
      more likely to receive assistance from medically trained personnel than women
      with no education. Women whose husbands had a lower status job were less likely
      to have safe delivery practices. The main contributing factors likely to affect
      delivery practices were mass media exposure, husband's occupation, education,
      antenatal care received, type of toilet facilities and household quality index.
      The results indicate several policy options. The high-risk group such as
      adolescents and higher aged women need special care and the existing health
      management system may be strengthened to create awareness among mothers of these
      groups for seeking appropriate measures from the beginning of pregnancy. There is
      need to ensure the availability of maternal health care centres for providing
      antenatal care and expand and improve the quality of normal delivery at home by
      trained providers and introduce post-partum visits. It is equally important that
      education for women is emphasised to bring about a lasting impact on the overall
      health condition of women.

PMID- 19402589
TI  - Despite hydroxyl/chloroquine's negative reputation, it may still be used by
      rheumatic patients in Africa.

PMID- 19402588
TI  - Challenges in malaria control in sub-Saharan Africa: the vaccine perspective.
AB  - Malaria is a life-threatening disease of public health importance, especially in
      sub-Saharan Africa. It is estimated that about 500 million cases of malaria occur
      annually and among these 1 million die annually. Children below five years and
      pregnant women are the most vulnerable groups. Several malaria control measures
      have been applied such as environmental improvements, use of insecticide
      impregnated nets, residual indoor spraying, early case detection and treatment
      with effective antimalarial drugs. However, the adaptation of vector and parasite
      has so far limited the effect of these interventions. The emergence of resistance
      against drugs and insecticides requires in response a steady stream of new
      interventions. Up to the beginning of this millennium, most sub-Saharan African
      countries have been using chloroquine (CQ) as the first-line antimalarial drug,
      which had to be replaced with sulphadoxine-pyrimethamine (SP) after resistant
      parasites had rendered CQ ineffective. Currently the first line treatment of
      malaria consists of combination therapy which includes an artemisinin derivative.
      The current approach appears robust but history has taught us to be alert and to
      expect resistance to emerge. There is a pressing need to develop and deploy
      complimentary strategies. Adding a protective vaccine to the existing control
      tools for malaria holds great promise yet no malaria vaccine has ever been
      licensed despite a large number of attempts. The complexity of malaria parasites
      and the ability of the parasite to suppress and evade immune responses are
      formidable challenges. Fortunately, there are several promising antimalarial
      vaccine candidates in the development pipeline. The most promising vaccine
      candidate is RTSS which is currently tested in various countries in sub-Saharan
      Africa, including two sites in Tanzania. There is a hope that malaria vaccines
      could be developed and deployed in malaria endemic communities. This article
      highlights the challenges of developing and deploying malaria vaccines.

PMID- 19402590
TI  - Was botched liver operation cause of death from embolism?

PMID- 19402592
TI  - NJ: Hospital protocol required 'code sheet': was "missing" 'code sheet' really
      missing?

PMID- 19402591
TI  - Why did nurse fail to chart & destroy her notes? Case on point: Healthcare
      Staffing Solutions v. Wilkinson, 0220.109 (2/19/2009)-FL.

PMID- 19402593
TI  - Claim that Pt. agreed to arbitration proved groundless. Case on point: Lisa Byrd
      Aurora Cares, LLC v. Simmons, 0320.178 (3/19/2009) So.2d-MS.

PMID- 19402594
TI  - 2008 National Caring Awards.
AB  - This year marks the 23rd anniversary of the creation of the Caring Institute as
      inspired by Mother Teresa. It also marks the 21st Annual National Caring Awards
      Ceremony. This year the Caring Institute Board of Trustees has chosen to honor
      five adults and five young people. They will receive their awards on April 7,
      2008, and simultaneously be inducted into the Hall of Fame for Caring Americans,
      located three blocks east of the U.S. Capitol in what was the first Washington,
      D.C. home of the great abolitionist Frederick Douglass. In addition to honoring
      individuals who are large of spirit, the Caring Awards express the hope that
      increased public awareness will lead to financial support for their charitable
      activities. The Institute also hopes that the honorees will be seen as role
      models to inspire and be emulated by others all across America.

PMID- 19402595
TI  - 2008 National Caring Awards youth winners.
AB  - Each year, the Caring Institute invites nominations of persons age 18 or younger
      for consideration as Young Adult Caring Award recipients. From the numerous
      applicants, the Caring Institute's prestigious Board of Trustees selects five
      award winners by secret ballot. This year's awardees are truly inspirational.
      Their accomplishments in caring for others are but a prologue of things to come.
      A short profile of each of these young people can be found on the following
      pages. Reading about them will give anyone confidence that the future of America
      is in good hands. To nominate a potential Caring Award Winner or to make a tax
      deductible donation, go to www.caring.org.

PMID- 19402596
TI  - A tribute to Deepak Chopra, M.D. Interview by Val J. Halamandaris.

PMID- 19402597
TI  - Childhelp: celebrating 50 years of fighting child abuse.

PMID- 19402598
TI  - A salute to Carl A. Hammerschlag, M.D. Interview by Val J. Halamandaris.

PMID- 19402600
TI  - The utilization of tachymetry in forensic medicine.
AB  - INTRODUCTION: Tachymetry is a geodetic method enabling to measure angles and
      distances. The aim of the work was to demonstrate alternatives of its utilization
      in daily forensic medicine practice. The work is dealing with confusing cases of
      gunshot injuries. It is impossible to determine the trajectory of the projectile,
      the sequence of gunshots, to identify shooting person etc. in these cases only on
      the base of autopsy findings and investigated circumstances. In these cases the
      investigation experiments on the crime scene in collaboration with the land
      surveyors were realized. The work presents two case reports. METHODS: For our
      measurements the electronic tachymeter TOPCON 211D was used. These were performed
      by the means of polar method in local coordinate system with relative heights. In
      the first case the position of victim was simulated by a figurant according to
      testimonies of witnesses and the accused. The second case dealed with suicide.
      RESULTS: In the first case there were two gunshots. The trajectory of the first
      gunshot was determined and the projectile was found. Hereby the most authentic
      testimony could be estimated. Also high grade probability of the relative
      position of the victim and the accused was figured out. In the case of suicide
      also the projectile was found and the position of the victim in the time of
      gunshot was determined. CONCLUSION: In the both case reports demonstrated the
      projectiles were not found by ballistics expert investigations. All questions of
      expert opinions could be answered only with the help of tachymetry. The advantage
      of this method is its good regional availability even at places far from
      specialized criminal investigation workplaces.

PMID- 19402599
TI  - Analysis of the tracheal contents using headspace gas chromatography-mass
      spectrometry to screen for accelerant use.
AB  - We describe here the usefulness of analysis of tracheal contents in a case of
      death by fire, which revealed that the deceased had used the accelerants. The
      analysis of tracheal contents provides useful information for the determination
      of the circumstances of the scene.

PMID- 19402601
TI  - [Shotgun injury--multiple pellets].
AB  - Both typical and less frequent features of gunshot wounds caused by shotguns are
      reported in the following article. The pattern of shotgun injury predominantly
      depends on gauge, choke, number and diameter of used pellets, muzzle-victim
      distance and on character of the afflicted area of the body. Characteristic
      ballistic properties of shotgun pellets, their wounding potential and
      significance in forensic patology are presented.

PMID- 19402603
TI  - Single-molecule fluorescence imaging of TiO(2) photocatalytic reactions.
AB  - Heterogeneous photocatalysts have both potential and demonstrated applications
      for use in the water-splitting reaction that produces hydrogen, the degradation
      of organic pollutants, the surface wettability conversion, etc. In this feature
      article, we have focused on the in-site observation of various reactive oxygen
      species (ROS), such as singlet oxygen ((1)O(2)) and the hydroxyl radical ((*)OH),
      generated by the photoexcitation of TiO(2) nanomaterials using single-molecule
      fluorescence spectroscopy. The spatially resolved photoluminescence (PL) imaging
      techniques enable us to determine the location of the (photo)catalytically active
      sites that are related to the heterogeneously distributed defects on the surface.
      We also present the results that revealed the formation and reaction dynamics of
      the photogenerated charge carriers in individual TiO(2) nanoparticles.
      Furthermore, we introduce the single-molecule single-mismatch detection of the
      nucleotide sequence upon the photoexcitation of a novel nanoconjugate consisting
      of TiO(2) and DNA on the basis of the mechanistic aspects. Notably, the present
      conjugates can recognize the difference in a single nucleotide. Consequently,
      this article provides a significant opportunity to understand the temporal and
      spatial distributions of ROS generated during the photoirradiation of TiO(2)
      nanomaterials and directly explore the microscopic world in many fields ranging
      from fundamental physics and chemistry to practical applications.

PMID- 19402602
TI  - Choice of the end functional groups in tri(p-phenylenevinylene) derivatives
      controls its physical gelation abilities.
AB  - New supramolecular organogels based on all-trans-tri(p-phenylenevinylene) (TPV)
      systems possessing different terminal groups, e.g., oxime, hydrazone,
      phenylhydrazone, and semicarbazone have been synthesized. The self-assembly
      properties of the compounds that gelate in specific organic solvents and the
      aggregation motifs of these molecules in the organogels were investigated using
      UV-vis, fluorescence, FT-IR, and 1H NMR spectroscopy, electron microscopy,
      differential scanning calorimetry (DSC), and rheology. The temperature variable
      UV-vis and fluorescence spectroscopy in different solvents clearly show the
      aggregation pattern of the self-assemblies promoted by hydrogen bonding, aromatic
      pi-stacking, and van der Waals interactions among the individual TPV units.
      Gelation could be controlled by variation in the number of hydrogen-bonding
      donors and acceptors in the terminal functional groups of this class of gelators.
      Also wherever gelation is observed, the individual fibers in gels change to other
      types of networks in their aggregates depending on the number of hydrogen-bonding
      sites in the terminal functions. Comparison of the thermal stability of the gels
      obtained from DSC data of different gelators demonstrates higher phase transition
      temperature and enthalpy for the hydrazone-based gelator. Rheological studies
      indicate that the presence of more hydrogen-bonding donors in the periphery of
      the gelator molecules makes the gel more viscoelastic solidlike. However, in the
      presence of more numbers of hydrogen-bonding donor/acceptors at the periphery of
      TPVs such as with semicarbazone a precipitation as opposed to gelation was
      observed. Clearly, the choice of the end functional groups and the number of
      hydrogen-bonding groups in the TPV backbone holds the key and modulates the
      effective length of the chromophore, resulting in interesting optical properties.

PMID- 19402604
TI  - Microfluidic fabrication of porous polymer microspheres: dual reactions in single
      droplets.
AB  - We report the microfluidic fabrication of macroporous polymer microspheres via
      the simultaneous reactions within single droplets, induced by UV irradiation. The
      aqueous phase of the reaction is the decomposition of H(2)O(2) to yield oxygen,
      whereas the organic phase is the polymerization of NOA 61, ethylene glycol
      dimethacrylate (EGDMA), and tri(propylene glycol) diacrylate (TPGDA) precursors.
      We first used a liquid polymer precursor to encapsulate a multiple number of
      magnetic Fe(3)O(4) colloidal suspension (MCS) droplets in a core-shell structure,
      for the purpose of studying the number of such encapsulated droplets that can be
      reliably controlled through the variation of flow rates. It was found that the
      formation of one shell with one, two, three, or more encapsulated droplets is
      possible. Subsequently, the H(2)O(2) solution was encapsulated in the same way,
      after which we investigated its decomposition under UV irradiation, which
      simultaneously induces the polymerization of the encapsulating shell. Because the
      H(2)O(2) decomposition leads to the release of oxygen, porous microspheres were
      obtained from a combined H(2)O(2) decomposition/polymer precursor polymerization
      reaction. The multiplicity of the initially encapsulated H(2)O(2) droplets
      ensures the homogeneous distribution of the pores. The pores inside the
      micrometer-sized spheres range from several micrometers to tens of micrometers,
      and the maximum internal void volume fraction can attain 70%, similar to that of
      high polymerized high internal phase emulsion (polyHIPE).

PMID- 19402605
TI  - Multifunctional patchy particles by glancing angle deposition.
AB  - The application of glancing angle deposition (GLAD) as a means to produce a
      variety of multifunctional patchy particles is reported. The GLAD technique has
      been previously used to produce anisotropic particles with an anisotropy
      dimension of "patchiness". Here, we extend the technique to produce
      multifunctional patchy particles with anisotropy dimensions of "patchiness",
      "branching", and "chemical ordering". To access the entire particle surface, a
      particle stamping technique is employed using a polydimethylsiloxane (PDMS)
      stamp. The particle stamping technique along with GLAD yields multifunctional
      patchy particles having patches on opposite poles. The potential of the developed
      techniques in producing a wide variety of surface-anisotropic particles with
      variable patch size, shape, and orientation is demonstrated.

PMID- 19402606
TI  - Purification and partial characterization of a lutein-binding protein from human
      retina.
AB  - Dietary intake of lutein and zeaxanthin appears to be advantageous for protecting
      human retinal and macular tissues from degenerative disorders such as age-related
      macular degeneration. Selective concentration of just two of the many dietary
      carotenoids suggests that uptake and transport of these xanthophyll carotenoids
      into the human foveal region are mediated by specific xanthophyll-binding
      proteins such as GSTP1 which has previously been identified as the zeaxanthin
      binding protein of the primate macula. Here, a membrane-associated human retinal
      lutein-binding protein (HR-LBP) was purified from human peripheral retina using
      ion-exchange chromatography followed by size-exclusion chromatography. After
      attaining 83-fold enrichment of HR-LBP, this protein exhibited a significant
      bathochromic shift of approximately 90 nm in association with lutein, and
      equilibrium binding studies demonstrated saturable, specific binding toward
      lutein with a K(D) of 0.45 muM. Examination for cross-reactivity with antibodies
      raised against known lutein-binding proteins from other organisms revealed
      consistent labeling of a major protein band of purified HR-LBP at approximately
      29 kDa with an antibody raised against silkworm (Bombyx mori) carotenoid-binding
      protein (CBP), a member of steroidogenic acute regulatory (StAR) protein family
      with significant homology to many human StAR proteins. Immunolocalization with
      antibodies directed against either CBP or GSTP1 showed specific labeling of rod
      and cone inner segments, especially in the mitochondria-rich ellipsoid region.
      There was also strong labeling of the outer plexiform (Henle fiber) layer with
      anti-GSTP1. Such localizations compare favorably with the distribution of macular
      carotenoids as revealed by resonance Raman microscopy. Our results suggest that
      HR-LBP may facilitate lutein's localization to a region of the cell subject to
      considerable oxidative stress.

PMID- 19402607
TI  - Reversible electrowetting on superhydrophobic double-nanotextured surfaces.
AB  - The paper reports on wetting, electrowetting (EW), and systematic contact angle
      hysteresis measurements after electrowetting of superhydrophobic silicon nanowire
      surfaces (NWs). The surfaces consist of C4F8-coated silicon nanowires grown on
      Si/SiO2 substrate. Different surfaces modulating (i) the dielectric layer
      thickness and (ii) the nanotexturation were investigated in this study. It was
      found that the superhydrophobic NWs display different EW behaviors according to
      their double nanotexturation with varying droplet impalement levels. Some
      surfaces exhibited a total reversibility to EW with no impalement (contact angle
      variation of 35+/-2 degrees at 190 VTRMS with deionized water), whereas other
      surfaces showed nonreversible behavior to EW with partial droplet impalement. A
      scenario is proposed to explain the unique properties of these surfaces.

PMID- 19402610
TI  - A new polymorph of N,N'-dimethylurea characterized by X-ray diffraction and first
      principles lattice dynamics calculations.
AB  - In this study we present a combined crystallographic and computational study of a
      new polymorph of N,N'-dimethylurea (DMU) with P2(1)2(1)2 space group symmetry,
      along with a revised theoretical study of the previously known phase in its
      corrected space group (Fdd2). X-ray diffraction studies show crystal structures
      that are very similar, differing only in the relative orientation of the hydrogen
      bonded molecular chains that are common to both phases. The vibrational spectra
      were obtained from B3LYP hybrid functional lattice dynamics calculations and
      compared with the experimental data for the known phase. The free-energy
      difference between the forms is derived from the Gamma-point optical mode
      frequencies, and amounts to less than 1 kJ mol(-1) across the temperature range
      of interest. The electronic densities-of-states of both phases are also computed,
      yielding only marginal differences in valence and conduction band compositions
      and band gap widths. Taken together, the results highlight the small but
      important differences separating the two crystal lattices.

PMID- 19402608
TI  - Sodium glycodeoxycholate and glycocholate mixed aggregates in gas and solution
      phases.
AB  - This paper deals with electrospray ionization mass spectrometry (ESIMS), small
      angle X-ray scattering (SAXS), and dynamic light scattering (DLS) measurements in
      order to provide information on the existence, aggregation, composition, and
      structure of the two-component aggregates of sodium glycocholate (NaGC) and
      sodium glycodeoxycholate (NaGDC) in the gas and solution phases. Five samples,
      containing 100% NaGC and 100% NaGDC, and NaGDC/NaGC molar ratios of 3 (75D), 1
      (50D), and 1/3 (25D), have been analyzed by ESIMS in positive-ion detection mode
      starting from 10(-3) and 10(-2) M total bile salt concentration in aqueous
      solutions. Generally, dimers or trimers prevail in the 100% NaGC or NaGDC
      samples, respectively, as observed in the preceding one-component ESIMS
      measurements and in agreement with the proposed micellar aggregate structures in
      aqueous solution. Moreover, it is observed that the composition of multimers in
      the samples 75D, 50D, and 25D deviates from the one expected on the basis of a
      random association of the monomers, the NaGDC contribution generally prevailing
      on the NaGC one. It happens also under the same percentage condition (50D
      sample), in agreement with a greater aggregation ability of NaGDC with respect to
      NaGC. SAXS and DLS data were recorded on six samples containing a NaGC+NaGDC 40
      mM total concentration, one bile salt having 40, 32, 24, 16, 8, and 0 mM
      concentration and the other the complementary one, keeping constant the NaCl
      concentration (0.6 M). The NaGDC 40 mM sample presents SAXS curves in agreement
      with a cylindrical shape of the aggregates as shown in a previous paper. For the
      bile salt mixtures, the progressive decrease of the sizes and change of the
      aggregate morphology, toward a globular-like geometry, are observed by increasing
      the NaGC fraction, thus confirming the hypothesis about the ability of trihydroxy
      salts to inhibit the growth of dihydroxy salt aggregates. Fits on the basis of
      cylindrical model can be accomplished for all the SAXS spectra, however, when the
      extracted cylinder parameters are used to estimate theoretical hydrodynamic radii
      a reasonable agreement is obtained only for the samples at high fraction of NaGDC
      (NaGDC>or=24 mM).

PMID- 19402611
TI  - Conformation of single block copolymer chain in two-dimensional microphase
      separated structure studied by scanning near-field optical microscopy.
AB  - The localization and orientation of the symmetric diblock copolymer chain in a
      quasi-two-dimensional microphase-separated structure were studied by scanning
      near-field optical microscopy (SNOM). In the monolayer of poly(isobutyl
      methacrylate)-block-poly(octadecyl methacrylate) (PiBMA-b-PODMA), the individual
      PiBMA subchains were directly observed by SNOM, and the center of mass (CM) and
      orientational angle relative to the phase interface were examined at the single
      chain level. It was found that the position of the CM and the orientation of the
      PiBMA subchain in the lamellar structure were dependent on the curvature of the
      PiBMA/PODMA interface. As the interface was bent toward the objective chain, the
      block chain preferred the CM position closer to the domain center, and the
      conformation was strongly oriented perpendicularly to the domain interface. With
      increase of the curvature, the steric hindrance among the block chain increases,
      resulting in the stretched conformation.

PMID- 19402609
TI  - Toward accurate microscopic calculation of solvation entropies: extending the
      restraint release approach to studies of solvation effects.
AB  - The evaluation of the solvation entropies is a major conceptual and practical
      challenge. On the one hand, it is interesting to quantify the factors that are
      responsible for the solvation entropies in solutions, whereas on the other, it is
      essential to be able to assess the contributions of the solvation entropies to
      the binding free energies and related properties. In fact, the solvation
      entropies are neglected in almost all of the studies of the binding entropies.
      The main problem is that widely used approaches, such as the quasiharmonic (QH)
      approximation, do not provide reliable results particularly in cases of shallow
      potential and multidimensional surfaces while brute force evaluations of the
      entropic effects by simulating temperature dependence of the free energy
      converges very slowly. This paper addresses the above issue by starting with an
      analysis of the factors that are responsible for the negative solvation entropy
      of ions, showing that it is not due to the change in the solvent vibration modes
      or to the solvent force constant but to the changes in the solvent
      configurational space upon change in the solute charges. We begin by clarifying
      that when one deals with aqueous solutions, it is easy to evaluate the
      corresponding entropic effect by the Langevin dipole (LD) treatment. However, in
      this work we are interested in developing a general microscopic tool that can be
      used to study similar effects in the proteins. To this end, we explore the
      ability of our restraint release (RR) approach to evaluate the solvation entropy.
      We start this analysis by reviewing the foundation of this approach and in
      particular, the requirements of minimizing the enthalpy contribution to the RR
      free energy. We then establish that our approach is not a specialized harmonic
      treatment but a rather powerful general approach. Moving to the main topic of
      this work, we demonstrate that the RR approach provides quantitative results for
      the solvation entropies of monovalent and divalent ions and effectively captures
      the physics of these entropic effects. The success of the current approach
      indicates that it should be applicable to the studies of the solvation entropies
      in the proteins and also, in examining hydrophobic effects. Thus, we believe that
      the RR approach provides a powerful tool for evaluating the corresponding
      contributions to the binding entropies and, eventually, to the binding free
      energies. This holds promise for extending the information theory modeling to
      proteins and protein-ligand complexes in aqueous solutions and consequently,
      facilitating computer-aided drug design.

PMID- 19402612
TI  - Recognition mechanism of theophylline-imprinted polymers: two-dimensional
      infrared analysis and density functional theory study.
AB  - Molecular imprinting polymers (MIPs) are synthetic materials having specific
      cavities tailored for a target molecule. Thoroughly understanding the molecular
      recognition mechanism is favorable for the rational design, preparation, and
      application of MIPs. In this work, theophylline (THO)-imprinted
      poly(acrylonitrile-co-acrylic acid) (PANCAA) films with acrylic acid (AA) as the
      functional monomer were fabricated and a set of concentration-dependent Fourier
      transform infrared (FT-IR) spectra were collected. Two-dimensional (2D)
      correlation analysis of the spectra and density functional theory (DFT)
      calculation were conducted to evaluate the molecular recognition mechanism. DFT
      at the B3LYP/6-31+G(d,p) level is efficacious to calculate the binding energies
      (DeltaE) and the theoretical vibration frequencies for the possible
      configurations of THO_AA complexes. An optimized cyclic hydrogen-bonded
      configuration (complex THO_AA1) has the highest binding energy (-16.63 kcal mol(
      1)) that is more stable than others. In addition, the experimental vibrations of
      the carbonyl groups in the FT-IR spectra were assigned on the basis of the DFT
      results. Moreover, methylacrylic acid (MAA) and caffeine (CAF) as compared
      analogues were also investigated. The DFT-based theoretical predictions are
      coincident with the reported results.

PMID- 19402613
TI  - First principles investigation of H addition and abstraction reactions on doped
      aluminum clusters.
AB  - We have investigated axial interactions of H(2) with Al(12)X (X = Mg, Al, and Si)
      clusters and found that homolytic dissociation leading to Al(12)XH and H atom
      proceeds without a barrier but is an extremely endothermic process. The
      calculated difference in energy of the addition and abstraction reactions
      indicates that any Al(12)X-based hydrogen storage technology that involves
      predissociation of H(2) will be limited by the competing processes. We have also
      discovered that while there is a modest barrier for dissociation of H(2) on a
      single Al(12)Mg cluster to give the dihydride, the process occurs spontaneously
      between two closely spaced Al(12)Mg clusters, resulting in the formation of two
      Al(12)MgH species. Doping of the cluster with an electropositive atom (Mg)
      enables the transfer of electron density to the Al cage, which enhances H(2)
      dissociation. The information gained can contribute to the design of novel solid
      state materials made of doped Al clusters, which may ultimately be suitable for
      catalytic processes.

PMID- 19402614
TI  - Mechanism of cellulose hydrolysis by inverting GH8 endoglucanases: a QM/MM
      metadynamics study.
AB  - A detailed understanding of the catalytic strategy of cellulases is key to
      finding alternative ways to hydrolyze cellulose to mono-, di-, and
      oligosaccharides. Endoglucanases from glycoside hydrolase family 8 (GH8) catalyze
      the hydrolysis of beta-1,4-glycosidic bonds in cellulose by an inverting
      mechanism believed to involve a oxacarbenium ion-like transition state (TS) with
      a boat-type conformation of the glucosyl unit in subsite -1. In this work,
      hydrolysis by Clostridium thermocellum endo-1,4-glucanase A was computationally
      simulated with quantum mechanics/molecular mechanics metadynamics based on
      density functional theory. Our calculations show that the glucosyl residue in
      subsite -1 in the Michaelis complex is in a distorted 2SO/2,5B ring conformation,
      agreeing well with its crystal structure. In addition, our simulations capture
      the cationic oxacarbenium ion-like character of the TS with a partially formed
      double bond between the ring oxygen and C5' carbon atoms. They also provide
      previously unknown structural information of important states along the reaction
      pathway. The simulations clearly show for the first time in GH8 members that the
      TS features a boat-type conformation of the glucosyl unit in subsite -1. The
      overall catalytic mechanism follows a DN*AN-like mechanism and a beta-2SO-->2,5B
      [TS]-->alpha-5S1 conformational itinerary along the reaction coordinate,
      consistent with the anti-periplanar lone pair hypothesis. Because of the
      structural similarities and sequence homology among all GH8 members, our results
      can be extended to all GH8 cellulases, xylanases, and other endoglucanases. In
      addition, we provide evidence supporting the role of Asp278 as the catalytic
      proton acceptor (general base) for GH8a subfamily members.

PMID- 19402615
TI  - Computational study on the photophysics of protonated benzene.
AB  - The reaction paths in the lowest excited electronic states relevant for the
      photophysics of protonated benzene, C(6)H(7)(+), have been explored by ab initio
      techniques of electronic structure theory. For this purpose, the first four
      excited singlet electronic states of C(6)H(7)(+) have been calculated at the
      CC2/cc-pVTZ level of theory. The CC2 approach has been validated by CASPT2 and TD
      DFT calculations. The calculated UV absorption spectrum is in good agreement with
      the experimental spectrum. It has been found that the out-of-plane and the in
      plane ring deformation leads in the excited states in an essential barrierless
      manner to a low-lying conical intersection between the lowest excited states and
      with the ground state, providing a mechanism for efficient radiationless
      deactivation, which is expected to quench luminescence of the isolated molecular
      ion.

PMID- 19402616
TI  - Explicit solvent effect on cation-pi interactions: a first principle
      investigation.
AB  - Sequential attachment of water molecules to cation-pi (Li+-benzene, K+-benzene,
      and Mg2+-benzene) systems reveals that the cation-pi interaction strength varies
      in opposite direction depending on the site of solvation of the cation-pi system.
      Solvation of the metal ion decreases its interaction energy with the pi system,
      while the solvation of the pi system increases its interaction energy with the
      metal ion. The cation binding to benzene clearly enhances the ability of aromatic
      protons to participate in hydrogen bonding with water molecules. The distance
      between the metal ion and centroid of the benzene inherently varies with the
      position of water molecules in the vicinity of cation-pi complex. Reduced
      variational space (RVS) analysis on bare and solvated cation-pi complexes
      indicates that the major contributions to the total interaction energy are coming
      from the polarization and charge transfer energy terms of the pi system.
      Topological atoms in molecules (AIM) analysis is performed to evaluate the nature
      of the cation-pi interaction. Good correlations are observed between interaction
      energies and charge density at the cage critical point of the cation-pi
      complexes.

PMID- 19402617
TI  - Understanding solvent effects on luminescent properties of a triple fluorescent
      ESIPT compound and application for white light emission.
AB  - A triple fluorescent compound, N-salicylidene-3-hydroxy-4-(benzo[d]thiazol-2
      yl)phenylamine (SalHBP), was dispersed in solid polymers and was developed as a
      white-light-emitting source in LED by using it as the first simple single
      compound with different configurations. The CIE coordinates were at (0.29, 0.35),
      close to those of pure white light. To explore speciation mechanisms in this
      single compound white light, SalHBP was dissolved in protic, nonpolar, and
      moderate polar solvent, respectively. Upon excitation, blue, green, and yellowish
      green emissions were observed from the three solutions at various temperatures.
      The conformation of SalHBP at room temperature was described by a Car-Parrinello
      molecular dynamics simulation. With the aid of hybrid density functional theory
      at the B3LYP/TZVP and PBE0/TZVP levels, three observed emission bands of SalHBP
      were assigned from the five most probable excited state conformations that were
      derived from four ground state conformations. The effect of solvent on the
      emission of SalHBP was summarized as a possibility for forming intermolecular
      hydrogen bonds between solvent and SalHBP molecules and competition between intra
      and intermolecular hydrogen bonds.

PMID- 19402618
TI  - Gracilioethers A-C, antimalarial metabolites from the marine sponge Agelas
      gracilis.
AB  - Three new antiprotozoan compounds, gracilioethers A-C (1-3), have been isolated
      from the marine sponge Agelas gracilis. Their structures were elucidated on the
      basis of spectroscopic and chemical methods. Gracilioethers A-C showed
      antimalarial activity against Plasmodium falciparum with IC(50) values of 0.5-10
      microg/mL, whereas gracilioether B (2) also showed antileishmanial activity.

PMID- 19402619
TI  - IR spectroelectrochemical cyclic voltabsorptometry and derivative cyclic
      voltabsorptometry.
AB  - In this paper, we report the IR (infrared) CVA (cyclic voltabsorptometry) and
      DCVA (derivative cyclic voltabsorptometry) spectroelectrochemical techniques to
      elucidate an electrochemical mechanism. First we set potassium ferrocyanide as an
      example to explain the validity of this method. Then the electrochemical redox of
      two compounds, 1,4-benzoquinone and 1,4-bis(2-ferrocenylvinyl)benzene, was
      selected to be examined with this method. 1,4-Benzoquinone exhibits two single
      electron waves in the cyclic voltammetric (CV) experiment, whereas two
      electroactive groups (Fc) are contained in p-(Fc-CH=CH)(2)BZ, but only one redox
      wave is observed. IR CVA results show that three IR absorption peaks in 1,4
      benzoquinone, 1232 cm(-1) (the absorption of final production), 1656 cm(-1) (the
      absorption of original reactant), and 1510 cm(-1) (the absorption of
      intermediate), and two IR absorption peaks in 1,4-bis(2-ferrocenylvinyl)benzene,
      1620 cm(-1) (the absorption of final oxide production) and 1589 cm(-1) (the
      absorption of intermediate), can be used to track the electron transfer. On the
      basis of the IR absorbance at the appropriate monitored wavelength (mentioned
      above), we can analyze simultaneously the concentration change of the
      corresponding redox transition during CV scans. Also the combination of the DCVA
      spectroelectrochemical technique with theory analysis allows reconstructing the
      current-potential (i-E) curve for each step of electron transfer. The
      reconstructed i-E curve can help us to understand the electron-transfer process.
      We believe IR CVA and DCVA spectroelectrochemical techniques can be applicable to
      the study of a wide range of complex electrochemistry processes.

PMID- 19402620
TI  - Mechanistic analysis of intramolecular free radical reactions toward synthesis of
      7-azabicyclo[2.2.1]heptane derivatives.
AB  - The mechanisms for the formation of conformationally constrained epibatidine
      analogues by intramolecular free radical processes have been computationally
      addressed by means of DFT methods. The mechanism and the critical effect of the 7
      nitrogen protecting group on the outcome of these radical-mediated cyclizations
      are discussed. Theoretical findings account for unexpected experimental results
      and can assist in the selection of proper precursors for a successful
      cyclization.

PMID- 19402621
TI  - On an electrode modified by a supramolecular ruthenium mixed valence
      (Ru(II)/Ru(III)) diphosphine-porphyrin assembly.
AB  - Three novel polymetallic ruthenium (III) meso-tetra(4-pyridyl)porphyrins
      containing peripheral "RuCl(3)(dppb)" moieties have been prepared and
      characterized. The X-ray structure of the tetraruthenated
      {NiTPyP[RuCl(3)(dppb)](4)} porphyrin complex crystallizes in the triclinic space
      group P1. This structure is discussed and compared with the crystal data for the
      mer-[RuCl(3)(dppb)(py)]. The {TPyP[RuCl(3)(dppb)](4)} and
      {CoTPyP[RuCl(3)(dppb)](4)} porphyrins were used to obtain electrogenerated films
      on ITO and glass carbon electrode surfaces, respectively. Such tetraruthenated
      porphyrins form films of a mixed-valence species
      {TPyP[Ru(dppb)](4)(muCl(3))(2)}(2n)(4n2+) and
      {CoTPyP[Ru(dppb)](4)(muCl(3))(2)}(2n)(4n2+) on the electrode surface. The
      modified electrode with {CoTPyP[RuCl(3)(dppb)](4)} is very stable and can be used
      to detect organic substrates such as catechol.

PMID- 19402622
TI  - A family of polynuclear clusters containing cyano-bridged T-shaped Fe(III)3M(II)
      (M = Cu, Co, Mn) metal cores: syntheses, structures, and magnetic properties.
AB  - A new family of polynuclear clusters containing the Fe(III)(3)M(II) cores
      [(Tp(4Bo))(6)Fe(6)(CN)(18)M(2)Na(2)(H(2)O)(16)] x 4 H(2)O (M = Cu, Co, Mn; 1-3)
      and [(Tp(4Bo))(6)Fe(6)(CN)(18)M(2)Na(2)(H(2)O)(12)(DMF)(4)] x H(2)O (M = Cu, Co,
      Mn; 4-6) have been synthesized and structurally characterized. Complexes 1-3
      crystallize in the P2(1)/c space group, and 4-6 crystallize in the P2(1)/n space
      group. All six complexes consist of two symmetry-related T-shaped
      [(Tp(4Bo))(3)(CN)(9)Fe(3)M](-) subunits linked by two Na(+) cations. Each
      polynuclear cluster in 1-6 strongly interacts with 12 adjacent such units through
      pi-pi interactions, leading to the formation of 3D 12-connected frameworks.
      Magnetic studies show appreciable magnetic anisotropies in compounds 1, 2, 4, and
      5. Antiferromagnetic interactions were observed in complexes 3 and 6.

PMID- 19402623
TI  - Nucleation of crystals from solution: classical and two-step models.
AB  - Crystallization is vital to many processes occurring in nature and in the
      chemical, pharmaceutical, and food industries. Notably, crystallization is an
      attractive isolation step for manufacturing because this single process combines
      both particle formation and purification. Almost all of the products based on
      fine chemicals, such as dyes, explosives, and photographic materials, require
      crystallization in their manufacture, and more than 90% of all pharmaceutical
      products contain bioactive drug substances and excipients in the crystalline
      solid state. Hence control over the crystallization process allows manufacturers
      to obtain products with desired and reproducible properties. We judge the quality
      of a crystalline product based on four main properties: size, purity, morphology,
      and crystal structure. The pharmaceutical industry in particular requires
      production of the desired crystal form (polymorph) to assure the bioavailability
      and stability of the drug substance. In solution crystallization, nucleation
      plays a decisive role in determining the crystal structure and size distribution.
      Therefore, understanding the fundamentals of nucleation is crucial to achieve
      control over these properties. Because of its analytical simplicity, researchers
      have widely applied classical nucleation theory to solution crystallization.
      However, a number of differences between theoretical predictions and experimental
      results suggest that nucleation of solids from solution does not proceed via the
      classical pathway but follows more complex routes. In this Account, we discuss
      the shortcomings of classical nucleation theory and review studies contributing
      to the development of the modern two-step model. In the two-step model that was
      initially proposed for protein crystallization, a sufficient-sized cluster of
      solute molecules forms first, followed by reorganization of that cluster into an
      ordered structure. In recent experimental and theoretical studies, we and other
      researchers have demonstrated the applicability of the two-step mechanism to both
      macromolecules and small organic molecules, suggesting that this mechanism may
      underlie most crystallization processes from solutions. Because we have observed
      an increase in the organization time of appropriate lattice structures with
      greater molecular complexity, we propose that organization is the rate
      determining step. Further development of a clearer picture of nucleation may help
      determine the optimum conditions necessary for the effective organization within
      the clusters. In addition, greater understanding of these processes may lead to
      the design of auxiliaries that can increase the rate of nucleation and avoid the
      formation of undesired solid forms, allowing researchers to obtain the final
      product in a timely and reproducible manner.

PMID- 19402624
TI  - Direct detection and characterization of chloride in the active site of the low
      pH form of sulfite oxidase using electron spin echo envelope modulation
      spectroscopy, isotopic labeling, and density functional theory calculations.
AB  - Electron spin echo envelope modulation (ESEEM) investigations were carried out on
      samples of the low-pH (lpH) form of vertebrate sulfite oxidase (SO) prepared with
      (35)Cl- and (37)Cl-enriched buffers, as well as with buffer containing the
      natural abundance of Cl isotopes. The isotope-related changes observed in the
      ESEEM spectra provide direct and unequivocal evidence that Cl(-) is located in
      close proximity to the Mo(V) center of lpH SO. The measured isotropic hyperfine
      interaction constant of about 4 MHz ((35)Cl) suggests that the Cl(-) ion is
      either weakly coordinated to Mo(V) at its otherwise vacant axial position, trans
      to the oxo ligand, or is hydrogen-bonded to the equatorial exchangeable OH
      ligand. Scalar relativistic all-electron density functional theory (DFT)
      calculations of the hyperfine and nuclear quadrupole interaction parameters,
      along with steric and energetic arguments, strongly support the possibility that
      Cl(-) is hydrogen-bonded to the equatorial OH ligand rather than being directly
      coordinated to the Mo(V).

PMID- 19402625
TI  - Effects of branching architecture and linker on the activity of hyperbranched
      polymer-drug conjugates.
AB  - Drug release from hyperbranched polymer-drug conjugates and the subsequent
      activity are influenced by the branching architecture and the linker. To gain an
      understanding of these effects, we used hyperbranched polyol and G4-OH
      polyamidoamine (PAMAM) dendrimer with methyl prednisolone (MP) as the model drug.
      The drug was conjugated to dendrimer or polyol using a glutaric acid (GA) or a
      succinic acid (SA) spacer. Drug payload was the highest with polyol, while in the
      case of dendrimer, a higher payload was achieved with the GA than the SA spacer.
      Cell uptake of the polymer conjugates in A549 lung epithelial cells was higher
      than that of the free drug, and the conjugates largely localized in the cytosol.
      The anti-inflammatory activity of polymer conjugated MP, as measured by
      inhibition of prostaglandin synthesis, was the highest for MP-SA-dendrimer
      conjugate, followed by MP-GA-polyol conjugate, and then MP-GA-dendrimer
      conjugate. This study suggests that the branching architecture and spacer
      influence the drug payload and pharmacological activity of a drug-nanopolymer
      conjugate, which may significantly influence the in vivo efficacy of these
      nanodevices. This has key implications in the eventual in vivo efficacy of these
      nanodevices.

PMID- 19402626
TI  - Guanidinylated polyethyleneimine-polyoxypropylene-polyoxyethylene conjugates as
      gene transfection agents.
AB  - Conjugates of linear and branched polyethyleneimine (PEI) and monoamine polyether
      Jeffamine M-2070 (PO/EO mol ratio 10/31, 2000 Da) were synthesized through
      polyether activation by cyanuric chloride followed by attachment to PEI and
      guanidinylation by 1H-pyrazole-carboxamidine hydrochloride. The resulting
      guanidinylated PEI-polyether conjugates (termed gPEI-Jeffamine) efficiently
      complexed plasmid DNA, and their polyplexes possessed enhanced colloidal
      stability in the presence of serum proteins. In vitro studies with mammalian CHO
      1, 3T3, and Cos-7 cell lines demonstrated improved transfection efficiency of the
      pCMVbeta-gal plasmid/gPEI-Jeffamine polyplexes. The guanidinylation of the amino
      groups of PEI and the conjugation of PEI with the Jeffamine polyether enhanced
      the conjugates' interaction with genetic material and reduced the cytotoxicity of
      the polyplexes in experiments with the L929 cell line.

PMID- 19402627
TI  - Ferromagnetic coupling by spin polarization in a trinuclear copper(II)
      metallacyclophane with a triangular cage-like structure.
AB  - A series of trinuclear copper(II) complexes of general formula A(6)[Cu(3)L(2)] x
      nH(2)O [L = benzene-1,3,5-tris(oxamate); A = Li(+) (n = 8), 1a; Na(+) (n = 11.5),
      1b; and K(+) (n = 8.5), 1c] have been synthesized, and they have been
      structurally and magnetically characterized. X-ray diffraction on single crystals
      of 1c shows the presence of three square-planar copper(II)-bis(oxamato) moieties
      which are connected by a double benzene-1,3,5-triyl skeleton to give a unique
      metallacyclophane-type triangular cage. The copper basal planes are virtually
      orthogonal to the two benzene rings, which adopt an almost perfect face-to-face
      alignment. Complexes 1a-c exhibit a quartet (S = 3/2) ground spin state resulting
      from the moderate ferromagnetic coupling (J values in the range of +7.3 to +16.5
      cm(-1)) between the three Cu(II) ions across the two benzene-1,3,5-tris(amidate)
      bridges [H = -J(S(1) x S(2) + S(2) x S(3) + S(3) x S(1)) with S(1) = S(2) = S(3)
      = S(Cu) = 1/2]. Density functional theory calculations on the S = 3/2 Cu(II)(3)
      ground spin state of 1c support the occurrence of a spin polarization mechanism
      for the propagation of the exchange interaction, as evidenced by the sign
      alternation of the spin density in the 1,3,5-substituted benzene spacers.

PMID- 19402628
TI  - Formation and calculations of the simple terminal triplet pnictinidene molecules
      N/MF(3), P/MF(3), and As/MF(3) (M = Ti, Zr, Hf).
AB  - Laser-ablated Ti, Zr, and Hf atoms react with NF(3), PF(3), or AsF(3) to produce
      triplet state terminal pnictinidene N/MF(3), P/MF(3), or As/MF(3) molecules,
      which are trapped in an argon matrix. Products are identified from infrared
      spectra and comparison to theoretically predicted vibrations. Density functional
      theory calculations converge to C(3v) symmetry structures for these lowest energy
      products. The two unpaired electrons in nitrogen 2p, phosphorus 3p, or arsenic 4p
      orbitals are shared in different small amounts with empty metal nd orbitals
      leading to very weak degenerate pialpha molecular orbitals based on bonding
      orbital analysis and spin density calculations. This weak pi bonding interaction
      with early transition metal group 4 nd orbitals is optimum for Zr with phosphorus
      3p orbitals.

PMID- 19402629
TI  - Antimalarial peroxide dyads from natural artemisinin and hydroxyalkylated 1,2,4
      trioxanes.
AB  - Three synthetic approaches to highly antimalarial peroxide dyads that are
      composed of the natural artemisinin part (either as dihydroartemisinin or
      artesunic acid components) and synthetic 1,2,4-trioxanes linked by ether or ester
      bridges are described. Photooxygenation is the key step to introduce the trioxane
      group initially or at the end of the reaction sequence, respectively.
      Dihydroartemisinin or artesunate coupling to hydroxyethyltrioxanes are the two
      processes that use intact peroxide units from the beginning, whereas the
      dihydroartemisinin-coupling to an allylic alcohol is a postphotooxygenation
      route, where the second trioxane ring is installed in the last step of the
      procedure.

PMID- 19402630
TI  - New 1alpha,25-dihydroxy-19-norvitamin D(3) compounds constrained in a single A
      ring conformation: synthesis of the analogues by ring-closing metathesis route
      and their biological evaluation.
AB  - Vitamin D compounds possessing A rings prohibited from flipping to the
      alternative chair form (i.e., analogues 2 and 26) were synthesized. The bicyclic
      fragment 22 consisting of the fused cyclohexane and dihydropyran rings was
      constructed via the ring-closing metathesis route. Also, a homologous synthon 23
      with an attached dihydropyran ring was successfully synthesized using this
      strategy. The carbonyl deprotection in 22 yielded cyclohexanone 5 that was
      subjected to Julia coupling with the anion of the phenylthiazoline sulfone 25. In
      the resulting isomeric 19-norvitamins 2 and 26, their A rings can exist only in
      the alpha- and beta-conformation. The analogue 26 was 300 times more active in
      binding to the vitamin D receptor protein, 30 times more effective in causing HL
      60 differentiation, and 10 times more active in transcription. These results
      confirm that the beta-chair form of the vitamin D ring A is necessary for the
      binding to the receptor.

PMID- 19402631
TI  - Evaluation of homology modeling of G-protein-coupled receptors in light of the
      A(2A) adenosine receptor crystallographic structure.
AB  - Homology modeling of the human A(2A) adenosine receptor (AR) based on bovine
      rhodopsin predicted a protein structure that was very similar to the recently
      determined crystallographic structure. The discrepancy between the experimentally
      observed orientation of the antagonist and those obtained by previous antagonist
      docking is related to the loop structure of rhodopsin being carried over to the
      model of the A(2A) AR and was rectified when the beta(2)-adrenergic receptor was
      used as a template for homology modeling. Docking of the triazolotriazine
      antagonist ligand ZM241385 1 was greatly improved by including water molecules of
      the X-ray structure or by using a constraint from mutagenesis. Automatic agonists
      docking to both a new homology modeled receptor and the A(2A) AR crystallographic
      structure produced similar results. Heterocyclic nitrogen atoms closely
      corresponded when the docked adenine moiety of agonists and 1 were overlaid. The
      cumulative mutagenesis data, which support the proposed mode of agonist docking,
      can be reexamined in light of the crystallographic structure. Thus, homology
      modeling of GPCRs remains a useful technique in probing the structure of the
      protein and predicting modes of ligand docking.

PMID- 19402632
TI  - A dihydrobenzofuran lignan induces cell death by modulating mitochondrial pathway
      and G2/M cell cycle arrest.
AB  - A dihydrobenzofuran lignan, the dimerization product of caffeic acid methyl
      ester, has shown pronounced antileishmanial and antiplasmodial activities. The
      present study showed the effect of this compound on cell cycle and apoptosis.
      Flow cytometric analysis revealed that the cells were arrested in the G2/M phase.
      Activation of caspase 3, but not caspase 8, generation of ROS, upstream of
      caspase-3, release of cytochrome c,increase in Bax level, and decrease in Bcl-2
      level suggested the involvement of mitochondrial damage. Loss of mitochondrial
      transmembrane potential independent of caspase activation further suggested the
      mode of apoptosis. Dihydrobenzofuran-mediated cell death was absent in Bcl-xL
      overexpressed cells. Overall, our results justify the role of dihydrobenzofuran
      lignan as potential antitumor agent, causing G2/M arrest and apoptosis involving
      the mitochondrial controlled pathway. These findings open promising insights as
      to how this specific dihydrobenzofuran lignan mediates cytotoxicity and may prove
      a molecular rationale for future therapeutic interventions in carcinogenesis.

PMID- 19402634
TI  - Tunable ferromagnetic spin ordering in boron nitride nanotubes with topological
      fluorine adsorption.
AB  - We find through first-principles calculations that fluorine atoms topologically
      adsorbed on boron nitride nanotubes induce long-ranged ferromagnetic spin
      ordering along the tube, offering strong spin polarization around the Fermi
      level. The spin polarization and magnetic moment increase significantly with
      decreasing tube radius, even giving rise to half-metal when the tube diameter is
      reduced to 3.3 A, while in a flat boron nitride sheet with the same topological
      fluorine arrangement the magnetic moment nearly disappears. This radius-dependent
      behavior is then developed into a local curvature modulation procedure to
      efficiently enhance or quench the ferromagnetic ordering, which enables the F
      BNNTs to function as piezomagnetic nanotubes. These findings suggest a new route
      to facilitate the design of tunable spin devices.

PMID- 19402633
TI  - A class of 2,4-bisanilinopyrimidine Aurora A inhibitors with unusually high
      selectivity against Aurora B.
AB  - The two major Aurora kinases carry out critical functions at distinct mitotic
      stages. Selective inhibitors of these kinases, as well as pan-Aurora inhibitors,
      show antitumor efficacy and are now under clinical investigation. However, the
      ATP-binding sites of Aurora A and Aurora B are virtually identical, and the
      structural basis for selective inhibition has therefore not been clear. We report
      here a class of bisanilinopyrimidine Aurora A inhibitors with excellent
      selectivity for Aurora A over Aurora B, both in enzymatic assays and in cellular
      phenotypic assays. Crystal structures of two of the inhibitors in complex with
      Aurora A implicate a single amino acid difference in Aurora B as responsible for
      poor inhibitory activity against this enzyme. Mutation of this residue in Aurora
      B (E161T) or Aurora A (T217E) is sufficient to swap the inhibition profile,
      suggesting that this difference might be exploited more generally to achieve high
      selectivity for Aurora A.

PMID- 19402635
TI  - Water overcomes methyl group directing effects in epoxide-opening cascades.
AB  - Water is an effective promoter of the endo-selective opening of trisubstituted
      epoxides, enabling related cascades leading to a variety of substituted ladder
      polyether structures. When used in conjunction with a tetrahydropyran-templated
      nucleophile, water can overcome the powerful electronic directing effect of a
      methyl substituent at either site of the epoxide, making water a uniquely
      versatile medium and promoter of epoxide opening.

PMID- 19402636
TI  - Electrochemically driven drug metabolism by membranes containing human cytochrome
      P450.
AB  - Rapid analyses of drug metabolism reactions by human cytochrome P450s (CYPs) that
      metabolize 95% of all current drugs are very important in drug development
      processes and effective therapies. Since CYPs need electrons to metabolize drugs,
      electrons supplied from electrodes to activate CYP molecules are expected to be
      very useful to develop rapid assay methods for CYP reactions. Although several
      studies on the direct electrochemistry of isolated and purified human CYPs have
      been reported, the use of microsomes (membranes) containing CYP is more suitable,
      because they are frequently used in drug research due to their easy preparation
      and low cost. Herein, we demonstrate electrons supplied from an electrode to
      microsomes containing CYP and CYP-reductase (CPR) on an electrode coated with
      hydrophobic thin films and observe electrochemically driven drug metabolisms by
      voltammetry for the first time. We tested the immobilization of microsomes on
      gold electrodes coated with several thiolates and found that microsomes
      immobilized on thin hydrophobic surfaces of aromatic compounds showed well
      defined redox peaks. Furthermore, electrochemically driven drug metabolism
      reactions of CYP3A4 were clearly observed by voltammetry, and these reactions
      were inhibited by a CYP3A4 inhibitor, ketoconazole. We also found that metabolism
      reactions were facilitated in the presence of CPR.

PMID- 19402637
TI  - Patterned growth of horizontal ZnO nanowire arrays.
AB  - We report an approach to fabricating patterned horizontal ZnO nanowire arrays
      with a high degree of control over their dimensionality, orientation, and
      uniformity. Our method combines electron beam lithography and a low temperature
      hydrothermal decomposition. This approach opens up possibilities to fabricate ZnO
      NW array based strain and force sensors, two-dimensional photonic crystals,
      integrated circuit interconnects, and alternative current nanogenerators.

PMID- 19402638
TI  - Suppression of human bone morphogenetic protein signaling by carboxylated single
      walled carbon nanotubes.
AB  - Effects of carbon nanotubes (CNTs) on living systems such as cells are crucial
      for the safe development of biosensors, drug carriers, or tumor imaging agents.
      We report here that SWCNT-COOH inhibited cell proliferation via a nonapoptotic
      mechanism, which is different from effects caused by pristine CNTs. On the basis
      of SWCNT-COOH's perturbations on cells, expression of genes and protein, and
      protein phosphorylations, we conclude that SWCNT-COOH suppresses Smad-dependent
      bone morphogenetic protein (BMP) signaling pathway and down-regulates Id
      proteins. These molecular events cause cell cycle arrest at G(1)/S transition and
      inhibit cell proliferation. The specific suppression of BMP signaling and Id
      proteins by SWCNT-COOH demonstrates nonapoptotic effects of functionalized CNTs
      on human cells. This finding may have potential therapeutic applications to treat
      human diseases related to Id proteins or BMP signaling such as breast cancer and
      bone diseases.

PMID- 19402639
TI  - Thermodynamic control of the electrocyclic ring opening of cyclobutenes: C=X
      substituents at C-3 mask the kinetic torquoselectivity.
AB  - The thermal ring-opening reactions of 4-phenyl-1,3,3-triethoxycarbonylcyclobutene
      and 4-methyl-1,3,3-triethoxycarbonylcyclobutene yield dienes that result from an
      unexpected selectivity for "inward" rotation of the phenyl and methyl groups.
      With 1-ethoxycarbonyl-4-phenylcyclobutene, "outward" rotation of the phenyl group
      occurs exclusively. Density functional theory was used to investigate the role of
      the 3,3-geminal diester groups and the origin of torquoselectivity in these
      electrocyclic reactions. The rules of torquoselectivity still hold, with a
      calculated 6-8 kcal/mol preference for outward rotation of the methyl and phenyl
      substituents. However, cyclization of the "out" dienes to pyran intermediates
      allows for isomerization and thermodynamic control of stereoselectivity.

PMID- 19402640
TI  - Physical characterization of lard partial acylglycerols and their effects on
      melting and crystallization properties of blends with rapeseed oil.
AB  - This work attempted to examine the effects of lard partial acylglycerols on the
      melting and crystallization properties of blends with lard and rapeseed oil (LR).
      Partial acylglycerols [lard-monoacylglycerols (lard-MAG) and lard-DAG] were found
      to result in different melting and crystallization properties of LR. Lard-MAG
      exerted slight inhibitory effect on crystallization of LR. Nevertheless, it was
      not statistically significant (P > 0.05). In fact, the presence of lard-MAG did
      not change the solid fat content (SFC) of LR. Lard-DAG, on the other hand,
      exerted different effects on the crystallization of LR depending on its
      concentration and degree of supercooling. The presence of a low concentration of
      lard-DAG was found to significantly (P < 0.05) delay nucleation and crystal
      growth velocity of LR at low degree of supercooling, which was reflected by a
      reduced Avrami constant (k) and SFC and increased half-time of crystallization
      (t(1/2)). Meanwhile, a high concentration of lard-DAG was found to promote
      nucleation and crystal growth in LR at low degrees of supercooling with increased
      k and SFC and decreased t(1/2). The characteristics of the blends may have
      correlations with their properties in potential meat applications.

PMID- 19402642
TI  - Hydroxyl group-directed organocatalytic asymmetric Michael addition of alpha,beta
      unsaturated ketones with alkenylboronic acids.
AB  - The organocatalytic asymmetric Michael addition of organoboronic acids to gamma
      hydroxy enones in the presence of an iminophenol-type thiourea catalyst is
      demonstrated. The hydroxyl group in the substrates plays a critical role in this
      reaction.

PMID- 19402641
TI  - Anti-Inflammatory and antiproliferative activities of trifolirhizin, a flavonoid
      from Sophora flavescens roots.
AB  - Trifolirhizin, a pterocarpan flavonoid, was isolated from the roots of Sophora
      flavescens, and its chemical structure was confirmed by (1)H and (13)C NMR and MS
      spectra. Its anti-inflammatory activity was examined in lipopolysaccharide (LPS)
      stimulated mouse J774A.1 macrophages. Trifolirhizin not only dose-dependently
      inhibited LPS-induced expression of pro-inflammatory cytokines including tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) but also inhibited
      lipopolysaccharide (LPS)-induced expression of cyclooxygenase-2 (COX-2). In
      addition, trifolirhizin showed in vitro inhibitory effects on the growth of human
      A2780 ovarian and H23 lung cancer cells. These results suggest that trifolirhizin
      possesses potential anti-inflammatory and anticancer activities.

PMID- 19402644
TI  - Electronic communication between immobilized ferrocenyl-terminated dendrimers.
AB  - Redox-active ferrocenyl-terminated dendrimers have been used to build robust and
      active interfaces in which the inherent properties of the dendrimers are
      preserved. The procedure is based on the preparation of a polyarylcarboxylate
      layer through the controlled reduction of aryldiazonium salts followed by strong
      adsorption of the dendrimers on the insulating layer. Scanning electrochemical
      microscopy was used to probe the transport properties as lateral charge
      diffusion. The experiments demonstrate that charge-transfer communication between
      the dendrimers inside the layer is fast and efficient, depending on the dendrimer
      generation.

PMID- 19402645
TI  - Vapor generation atomic absorption spectrometric determination of cadmium in
      environmental samples with in-line anion exchange separation.
AB  - A novel in-line anion exchange separation method is described for the removal of
      Mn(2+), Fe(3+), Ni(2+), Co(2+), Cu(2+), Zn(2+), and Pb(2+) from Cd(2+) and for
      its subsequent determination by vapor generation atomic absorption spectrometry.
      High Cd(2+) retention efficiency and maximum exclusion of other metal ions were
      achieved by using Cl(-), Br(-), or I(-) loaded strong base anion exchange resin
      and fiber in chloride medium. SO(4)(2-) and NO(3)(-) affected the retention of
      Cd(2+) on Cl(-) or Br(-) loaded exchangers but were beneficial for elution from
      I(-) loaded exchangers. Fast and efficient elution from the exchangers was
      achieved by using ethylenediamine solution. The removal of Zn(2+) was unnecessary
      as it prevents a decline in the sensitivity of cadmium response when
      ethylenediamine and high acid concentration were used. Under optimum conditions,
      the achievable detection limits (3sigma) with sample loadings of 0.48 and 9.6 mL
      were 40 ng L(-1) and 3 ng L(-1), respectively. Interference of residual organic
      matrix, in sample digests, with the separation and retention of cadmium were
      eliminated by use of microwave assisted digestion. The method was successfully
      applied to the determination of Cd in river sediment, fish liver, and water
      samples.

PMID- 19402643
TI  - pH- and photo-switched release of guest molecules from mesoporous silica
      supports.
AB  - This paper proposes a new nanoscopic molecular movable gate-like functional
      hybrid system consisting of nanoscopic MCM-41-based material functionalized onto
      pore outlets with a saccharide derivative capable of interacting with boronic
      acid functionalized gold nanoparticles (AuNPs) acting as nanoscopic caps. The
      gating mechanism involves the reversible reaction between polyalcohols and
      boronic acids to form boronate esters. Functionalized AuNPs thus act as a
      suitable nanoscopic cap via the reversible formation of the corresponding
      boroester bonds with the saccharide derivative anchored on the external surface
      of the mesoporous silica-based solid. The developed platform operates in aqueous
      solution and can be triggered by two simple external stimuli such as pH changes
      or light. The hydrolysis of the boroester bond takes place at pH 3, which results
      in rapid delivery of the safranine cargo from the pore voids into the aqueous
      solution. However, at pH 5 the pores are capped with nanoparticles and the
      delivery is strongly inhibited. The kinetics of the delivery was studied at pH =
      3, assuming a simple diffusion process and that the kinetics of guest release
      from the pore voids of the hybrid material can be explained by the Higuchi model.
      It is possible to deliver the cargo in small portions by carrying out on-off
      aperture cycles via changing the pH from 3 to 5. AuNPs also open the possibility
      of employing light as a suitable stimulus for release procedures using the AuNPs'
      capacity for raising their temperature locally by absorption of laser light. The
      plasmonic heating using a Nd:YAG laser at 1064 nm results in the cleavage of the
      boronic ester linkage that anchors the nanoparticles to the surface of the
      mesoporous silica-based material, allowing the release of the entrapped guests.
      Further studies also demonstrated that it is possible to fine-tune the amount of
      cargo delivered by simply controlling the laser irradiation opening the
      possibility to designing laser-induced pulsatile release supports.

PMID- 19402646
TI  - Fiber optic sensor for simultaneous determination of atmospheric nitrogen
      dioxide, ozone, and relative humidity.
AB  - We describe a novel optical sensor for the simultaneous measurement of
      atmospheric nitrogen dioxide (NO(2)), ozone (O(3)), and relative humidity (RH). A
      transparent backing thin layer silica gel chromatographic plate impregnated with
      8-amino-1-naphthol-5-sulfonic acid (ANS) is used as the collection/sensor
      element. The plate transmittance is probed by three discrete light emitting
      diodes (LEDs) centered, respectively, at 442, 525, and 850 nm. The transmission
      of the plate changes reversibly across visible to NIR wavelengths as the RH
      around the plate changes; this is the basis for a limited-resolution RH sensor.
      The ANS on the plate reacts to form brown and pink colored products,
      respectively, when it reacts with NO(2) and O(3). The sample air impinges on the
      plate via an entrance nozzle. The LEDs are alternately turned on in a
      preprogrammed manner and the light is brought to the impregnated face of the
      plate by a three-legged fiber optic. The transmitted light is detected on the
      obverse side of the plate. The 850 nm signal provides the RH value and optionally
      serves as the reference measurement for the other two wavelengths; the NO(2) and
      O(3) reaction products do not absorb at this wavelength. The absorbance at 442
      and 525 nm, thus referenced against 850 nm, are used to obtain NO(2) and O(3)
      concentrations from a pair of simultaneous equations. For a sampling period of 5
      min, the limits of detection (LOD) based on 3 times the standard deviation of
      blank responses were 0.64 and 0.42 ppbv for NO(2) and O(3), respectively. Data
      obtained with collocated commercial instruments (O(3) induced chemiluminescence
      analyzer for NO(2) and UV-absorption for O(3)) show good agreement. Overall, this
      provides a viable affordable approach for inexpensive measurement of atmospheric
      NO(2) and O(3).

PMID- 19402647
TI  - Optimized transport setup for high repetition rate pulse-separated analysis in
      laser ablation-inductively coupled plasma mass spectrometry.
AB  - An optimized laser ablation setup, proposed for high repetition rate inductively
      coupled plasma mass spectrometry (ICPMS) analyses such as 2D imaging or depth
      profiling, is presented. For such applications, the particle washout time needs
      to be as short as possible to allow high laser pulse frequencies for reduced
      analysis time. Therefore, it is desirable to have an ablation setup that operates
      as a laminar flow reactor (LFR). A top-down strategy was applied that resulted in
      the present design. In the first step, a previously applied ablation setup was
      analyzed on the basis of computational fluid dynamics (CFD) results presented by
      D. Autrique et al. (Spectrochim. Acta, B 2008, 63, 257-270). By means of CFD
      simulations, the design was modified in such a way that it operated in the LFR
      regime. Experimental results demonstrate that the current design can indeed be
      regarded as an LFR. Furthermore, the operation under LFR conditions allowed some
      insight into the initial radial concentration distribution if the experimental
      ICPMS signal and analytical expressions are taken into account. Recommendations
      for a modified setup for more resilient spatial distributions are given. With the
      present setup, a washout time of 140 ms has been achieved for a 3% signal area
      criterion. Therefore, 7 Hz repetition rates can be applied with the present
      setup. Using elementary formulas of the analytical model, an upper bound for the
      washout times for similar setups can be predicted. The authors believe that the
      presented setup geometry comes close to the achievable limit for reliable short
      washout times.

PMID- 19402648
TI  - Numerical simulation of diffusion processes at recessed disk microelectrode
      arrays using the quasi-conformal mapping approach.
AB  - In this work, we present a theoretical analysis of diffusion processes at arrays
      of recessed microelectrodes and evaluate the dependence of these processes on the
      main geometrical parameters (distance between electrodes in the array and slope
      of side walls of conical recesses) of this complex system. To allow for faster
      computation time and excellent accuracy, numerical simulations were performed
      upon transforming the real space allowed for diffusion using a quasi-conformal
      mapping introduced for this array geometry in our previous work (Amatore, C.,
      Oleinick, A. I. and Svir, I. J. Electroanal. Chem. 2006, 597, 77-85). The applied
      quasi-conformal mapping is perfectly suited to the considered microelectrode
      array geometry and ensures that the abrupt change of boundary conditions
      reflecting the contorted geometries of the considered microelectrode array are
      treated efficiently and precisely in the simulations.

PMID- 19402649
TI  - Seeding-induced self-assembling protein nanowires dramatically increase the
      sensitivity of immunoassays.
AB  - Aiming to build a supersensitive and easily operable immunoassay, bifunctional
      protein nanowires were generated by seeding-induced self-assembling of the yeast
      amyloid protein Sup35p that genetically fused with protein G and an enzyme
      (methyl-parathion hydrolase, MPH), respectively. The protein nanowires possessed
      a high ratio of enzyme molecules to protein G, allowing a dramatic increase of
      the enzymatic signal when protein G was bound to an antibody target. As a result,
      a 100-fold enhancement of the sensitivity was obtained when applied in the
      detection of the Yersinia pestis F1 antigen.

PMID- 19402650
TI  - Contamination-free transmission electron microscopy for high-resolution carbon
      elemental mapping of polymers.
AB  - Specimen contamination induced by electron beam irradiation has long been a
      serious problem for high-resolution imaging and analysis by a transmission
      electron microscope (TEM). It creates a deposition of carbonaceous compounds on a
      region under study, causing the loss of resolution. We developed a method to
      reduce the beam-induced specimen contamination by cleaning a TEM with activated
      oxygen radicals. The hydrocarbon contaminants accumulated inside the microscope's
      chamber can be etched away by gentle chemical oxidation without causing any
      damage to the microscope. The "contamination-free TEM" can effectively suppress
      the deposition of carbon-rich products on a specimen and therefore enables us to
      perform high-resolution carbon elemental mapping by energy-filtering transmission
      electron microscopy (EFTEM). In this study, we investigated the structure of
      polymer brushes immobilized on a silica nanoparticle (SiNP), of which molecular
      weight, length, and density of the brushes had been characterized in detail. The
      isolated particle showed the stretched formations of the polymer chains growing
      from the surface, while the densely distributed particles showed the connection
      of the polymer chains between neighboring particles. Moreover, the polymer brush
      layer and the surface initiator could be differentiated from each other by the
      component-specific contrast achieved by electron spectroscopic imaging (ESI). The
      contamination-free TEM can allow us to perform high-resolution carbon mapping and
      is expected to provide deep insights of soft materials' nanostructures.

PMID- 19402651
TI  - Silica-shell/oil-core microcapsules with controlled shell thickness and their
      breakage stress.
AB  - The encapsulation of one material by another, to form core-shell particles
      (microcapsules), has many applications, principally the containment, protection,
      and distribution of an active material. This work describes the development of
      core-shell particles with silicone oil cores and solid silica-like shells of
      controlled thickness. Oligomeric polydimethylsiloxane (PDMS) emulsions are
      employed as the core templates for the formation of the solid shells. The core
      templates are prepared by the surfactant-free, condensation polymerization of
      diethoxydimethylsilane (DEODMS) that leads to the formation of monodisperse
      silicone oil/water emulsions. Solid silica-like, composite shells were formed
      through condensation of tetraethoxysilane (TEOS) and DEODMS onto the core
      templates. The shell thickness may be controlled by manipulation of relative TEOS
      and DEODMS concentrations or by quenching the shell development step. It is
      possible to incorporate a dye into the core prior to shell formation, which does
      not seem to permeate the shell. The coated PDMS particles were subjected to a
      controlled compression stress using a micromanipulation technique. The capsule
      breaking force was found to be proportional to the shell thickness, as quantified
      using scanning electron microscopy (SEM) ultramicrotomy.

PMID- 19402652
TI  - Sensitivity of crescent-shaped metal nanoparticles to attachment of dielectric
      colloids.
AB  - The response of the plasmonic resonances of crescent-shaped nanoparticles to the
      attachment of a dielectric colloidal particle was investigated. The colloid
      serves as a model analyte which is easy to handle and allows for benchmarking of
      the sensing capabilities of plasmonic resonators. A clear red shift of the
      resonances is observed in agreement with the prediction from numerical
      simulations. From the response for different colloid positions, we obtain
      information on the nanoscale near field distribution. A field localization to
      length scales of 20 nm is proven directly. All resonators under study show a
      comparable response which is important for possible sensing application. We
      estimate that a further increase of the sensitivity by a factor of 8 would allow
      for label-free single biomolecule detection.

PMID- 19402653
TI  - MnO2/CNT supported Pt and PtRu nanocatalysts for direct methanol fuel cells.
AB  - Pt/MnO2/carbon nanotube (CNT) and PtRu/MnO2/CNT nanocomposites were synthesized
      by successively loading hydrous MnO2 and Pt (or PtRu alloy) nanoparticles on CNTs
      and were used as anodic catalysts for direct methanol fuel cells (DMFCs). The
      existence of MnO2 on the surface of CNTs effectively increases the proton
      conductivity of the catalyst, which then could remarkably improve the performance
      of the catalyst in methanol electro-oxidation. As a result, Pt/MnO2/CNTs show
      higher electrochemical active surface area and better methanol electro-oxidation
      activity, compared with Pt/CNTs. As PtRu alloy nanoparticles were deposited on
      the surface of MnO2/CNTs instead of Pt, the PtRu/MnO2/CNT catalyst shows not only
      excellent electro-oxidation activity to methanol with forward anodic peak current
      density of 901 A/gPt but also good CO oxidation ability with lower preadsorbed CO
      oxidation onset potential (0.33 V vs Ag/AgCl) and peak potential (0.49 V vs
      Ag/AgCl) at room temperature.

PMID- 19402655
TI  - Influence of the structure and composition of mono- and dialkyl phosphate
      mixtures on aluminum complex organogels.
AB  - The rheological properties and structure of organogels formed by the in situ
      complexation and self-assembly of aluminum isopropoxide and didodecyl phosphate
      surfactant in decane are investigated as mono-n-dodecyl phosphoric acid and bis(2
      ethylhexyl) phosphoric acid complexing agents are added. At low loadings, the
      bulky bis(2-ethylhexyl) additive disrupts the physical gel structure by changing
      the packing around the aluminum centers, weakening the transition from
      viscoelastic fluid to physical network of branched cylinders, and completely
      suppresses gelation at high loadings. Monododecyl phosphate affects coordination
      at the Al center. At low substitution, it shifts the composition at which the
      transition to a physical gel occurs while simultaneously improving long-term
      stability. Structures deduced from the rheological response are confirmed by
      small-angle neutron scattering, which shows that the aggregates are locally
      cylindrical and molecularly thin at all compositions studied, although the cross
      section of the cylinders depends on the alkyl chain structure and composition of
      the organic phosphate mixtures.

PMID- 19402656
TI  - Structure and properties of functionalized bithiophenesilane monodendrons.
AB  - This study reports a focal group modification of bithiophenesilane monodendrons
      and its effect on their molecular ordering in solution, bulk, and surface. We
      investigated hydrophobic MDn monodendrons and COOH-functionalized MDn-COOH
      monodendrons with generations, n=0, 1, 2, and 3. We observed that increasing the
      number of branches led to the progressive blue shift, indicating distorted
      packing of branched thiophene fragments of MDn. In contrast, MDn-COOH
      monodendrons showed a progressive red shift with the increasing generation
      number, indicating gradual domination of sigma-pi interactions. Moreover, the
      introduction of a focal carboxylic group resulted in the formation of a highly
      crystalline state for the linear MD0-COOH compound with separated alkyl tail
      thiophene packing, which limits pi-pi interactions. Increasing branching in the
      COOH-containing monodendrons resulted in a hydrophobic-hybrophilic balance
      sufficient to form stable and uniform Langmuir monolayers at the air-water at a
      modest surface pressure (<10 mN/m), easily transferrable to a solid substrate.
      However, a further increase in the thickness of the surface layers from tens to
      hundreds of nanometers via Langmuir-Blodgett (LB) deposition or spin casting is
      limited by the formation of globular surface aggregates because of strong
      intermolecular interactions. A modest red shift observed for condensed Langmuir
      monolayers indicates densification of thiophene branches and limited
      intramonolayer crystallization, which preserves photoluminescence. In contrast,
      thicker surface films showed a significant red shift, confirming a dense
      molecular packing with strong pi-pi interactions, which results in
      photoluminescence quenching.

PMID- 19402654
TI  - Synthetic peptides of hepatitis G virus (GBV-C/HGV) in the selection of putative
      peptide inhibitors of the HIV-1 fusion peptide.
AB  - The GB virus C or hepatitis G virus (GBV-C/HGV) is a single-stranded positive
      sense RNA virus that belongs to the Flaviviridae family. Recent years have seen
      the publication of numerous works in which coinfection with GBV-C/HGV and HIV has
      been associated with slower progression of the illness and a higher survival rate
      of patients once AIDS has developed. The mechanism by which the GBV-C/HGV virus
      has a "protective effect" in patients with HIV has still not been defined. Study
      of the interaction of the GBV-C/HGV and HIV viruses could lead to the development
      of new therapeutic agents for the treatment of AIDS. Given that the mechanism
      responsible for the beneficial effect exercised by the GBV-C/HGV virus in the
      course of HIV infection has not been defined, the present work is intended as a
      study of the structure and interactions between the fusion peptide of HIV-1,
      gp41(1-23), and synthetic peptide sequences of the E2 envelope protein of GBV
      C/HGV using biophysical techniques. Our results highlight that the E2(269-286)
      sequence interacts with the target fusion peptide of HIV-1 and modifies its
      conformation.

PMID- 19402657
TI  - Construction of highly ordered lamellar nanostructures through Langmuir-Blodgett
      deposition of molecularly thin titania nanosheets tens of micrometers wide and
      their excellent dielectric properties.
AB  - Exfoliated unilamellar titania nanosheets of Ti(0.87)O(2) with a lateral size of
      10-30 microm were deposited layer-by-layer onto various substrates by Langmuir
      Blodgett procedure to produce a highly ordered lamellar nanofilms. The nanosheets
      dispersed in an aqueous suspension containing quaternary ammonium ions as a
      supporting electrolyte floated spontaneously at the air/liquid interface, and
      they were successfully transferred onto the substrate after surface compression.
      Neat tiling of the nanosheets could be realized at an optimized surface pressure.
      The film thus obtained was exposed to UV light to turn the substrate surface
      hydrophilic, which was helpful for stable repetition of monolayer deposition.
      Layer-by-layer growth was confirmed by UV-visible absorption spectra, which
      showed progressive enhancement of an absorption band due to the nanosheet. Cross
      sectional transmission electron microscopy images visualized the ultrathin film
      homogeneously deposited on the substrate surface and a lamellar fringe of the
      layer-by-layer assembled nanosheets was clearly resolved at a higher
      magnification. X-ray diffraction data on the films showed sharp basal reflections
      up to the seventh order, and Williamson-Hall analysis of the pattern indicated
      that the film was coherent across the total thickness with respect to X-ray and
      that the lattice strain was extremely small. In addition, the first basal
      reflection was accompanied by small satellite peaks, which are accounted for by
      the Laue interference function. All these features clearly indicate the formation
      of a highly ordered lamellar nanostructure of the titania nanosheets comparable
      to artificial lattice films produced via modern vapor-phase deposition processes.
      The obtained films showed superior dielectric and insulating properties as a
      reflection of the highly organized film nanoarchitecture.

PMID- 19402658
TI  - Conformation preorganization: effects of S20G mutation on the structure of human
      islet amyloid polypeptide segment.
AB  - The missense mutation S20G in the human islet amyloid polypeptide (hIAPP) is
      supposed to be associated with the early onset of type II diabetes (T2DM) in
      Asian population. How such a single-point mutation induces variation of the
      conformation distribution and the amyloidogenic properties of hIAPP is still
      unknown. We studied the conformational ensembles of hIAPP segment 15-27 in both
      wild type and the S20G mutant type by performing extensive replica exchange
      molecular dynamics simulations in explicit solvent model. Our results reveal that
      the residue G20 initiates a turnlike structure in the neighborhood, facilitating
      the formation of long-ranged contacts. Moreover, we find that the point mutation
      favors protofibril model of full length hIAPP suggested recently based on
      experimental measurements. Such a conformational preorganization will decrease
      the entropy cost during the process of peptide self-assembly, which is a possible
      explanation of the faster fibrillation of hIAPP S20G mutant than that of the wild
      type found by experiments.

PMID- 19402659
TI  - A simple, universal colorimetric assay for endonuclease/methyltransferase
      activity and inhibition based on an enzyme-responsive nanoparticle system.
AB  - An enzyme responsive nanoparticle system that uses a DNA-gold nanoparticle (AuNP)
      assembly as the substrate has been developed for the simple, sensitive, and
      universal monitoring of restriction endonucleases in real time. This new assay
      takes advantage of the palindromic recognition sequence of the restriction
      nucleases and the unique optical properties of AuNPs and is simpler than the
      procedure previously described by by Xu et al. (Angew. Chem. Int. Ed. Engl. 2007,
      46, 3468-3470). Because it involves only one type of ssDNA modified AuNPs, this
      assay can be directed toward most of the endonucleases by simply changing the
      recognition sequence found within the linker DNA. In addition, the endonuclease
      activity could be quantitatively analyzed by the value of the reciprocal of
      hydrolysis half time (t(1/2)(-1)). Furthermore, our new design could also be
      applied to the assay of methyltransferase activity since the methylation of DNA
      inhibits its cleavage by the corresponding restriction endonuclease, and thus,
      this new methodology can be easily adapted to high-throughput screening of
      methyltransferase inhibitors.

PMID- 19402660
TI  - Universal (switchable) RAFT agents.
AB  - The polymerization of most monomers that are polymerizable by radical
      polymerization can be controlled by the reversible addition-fragmentation chain
      transfer (RAFT) process. However, it is usually required that the RAFT agent be
      selected according to the types of monomer being polymerized. Thus, RAFT agents
      (dithioesters, trithiocarbonates) suitable for controlling polymerization of
      "more activated" monomers (MAMs; e.g., styrene, acrylates, methacrylates, etc.)
      tend to inhibit polymerization of "less activated" monomers (LAMs; e.g., vinyl
      acetate, N-vinylpyrrolidone, etc.). Similarly RAFT agents suitable for
      polymerizations of LAMs (xanthates, certain dithiocarbamates) tend to give little
      or poor control over polymerizations of MAMs. We now report a new class of
      "switchable" RAFT agents, N-(4-pyridinyl)-N-methyldithiocarbamates, that provide
      excellent control over polymerization of LAMs and, after addition of 1 equiv of a
      protic or Lewis acid, become effective in controlling polymerization of MAMs,
      allowing the synthesis of poly(MAM)-block-poly(LAM) with narrow molecular weight
      distributions.

PMID- 19402661
TI  - Crystal-to-crystal transformation from antiferromagnetic chains into a
      ferromagnetic diamondoid framework.
AB  - Pink crystals composed of antiferromagnetic chains (1) can be transformed into
      blue crystals composed of a ferromagnetic diamondoid framework (2) with
      structural and magnetic changes.

PMID- 19402662
TI  - Effect of cage charges on multiphoton absorptions: first-principles study on
      metallofullerenes Sc(2)C(2)@C(68) and Sc(3)N@C(68).
AB  - A combined method of the time-dependent density functional theory (TDDFT) and sum
      overstate (SOS) formula was implemented to model multiphoton absorption spectra,
      including two-photon absorption (2PA) and three-photon absorption (3PA), of
      Sc(2)C(2)@C(68) and Sc(3)N@C(68) endohedral metallofullerenes (EMFs). This method
      has been proved to be effective by comparisons between the calculated and
      experimental results of trans-4,4'-bis[diphenylamino]stilbene. It was found that
      the multiphoton absorption cross sections were larger for Sc(2)C(2)@C(68) than
      that of Sc(3)N@C(68). The electronic origin of multiphoton absorption has been
      identified with respect to the molecular orbitals involved in charge transfer
      process. It shows that the increase of pi-charges on the cage of C(68) results in
      a large multiphoton absorption cross section in EMFs.

PMID- 19402663
TI  - Estimations of global warming potentials from computational chemistry
      calculations for CH(2)F(2) and other fluorinated methyl species verified by
      comparison to experiment.
AB  - In this work, the global warming potential (GWP) of methylene fluoride
      (CH(2)F(2)), or HFC-32, is estimated through computational chemistry methods. We
      find our computational chemistry approach reproduces well all phenomena important
      for predicting global warming potentials. Geometries predicted using the B3LYP/6
      311g** method were in good agreement with experiment, although some other
      computational methods performed slightly better. Frequencies needed for both
      partition function calculations in transition-state theory and infrared
      intensities needed for radiative forcing estimates agreed well with experiment
      compared to other computational methods. A modified CBS-RAD method used to obtain
      energies led to superior results to all other previous heat of reaction estimates
      and most barrier height calculations when the B3LYP/6-311g** optimized geometry
      was used as the base structure. Use of the small-curvature tunneling correction
      and a hindered rotor treatment where appropriate led to accurate reaction rate
      constants and radiative forcing estimates without requiring any experimental
      data. Atmospheric lifetimes from theory at 277 K were indistinguishable from
      experimental results, as were the final global warming potentials compared to
      experiment. This is the first time entirely computational methods have been
      applied to estimate a global warming potential for a chemical, and we have found
      the approach to be robust, inexpensive, and accurate compared to prior
      experimental results. This methodology was subsequently used to estimate GWPs for
      three additional species [methane (CH(4)); fluoromethane (CH(3)F), or HFC-41; and
      fluoroform (CHF(3)), or HFC-23], where estimations also compare favorably to
      experimental values.

PMID- 19402664
TI  - Glucose promoiety enables glucose transporter mediated brain uptake of ketoprofen
      and indomethacin prodrugs in rats.
AB  - The brain uptake of solutes is efficiently governed by the blood-brain barrier
      (BBB). The BBB expresses a number of carrier-mediated transport mechanisms, and
      new knowledge of these BBB transporters can be used in the rational targeted
      delivery of drug molecules for active transport. One attractive approach is to
      conjugate an endogenous transporter substrate to the active drug molecule to
      utilize the prodrug approach. In the present study, ketoprofen and indomethacin
      were conjugated with glucose and the brain uptake mechanism of the prodrugs was
      determined with the in situ rat brain perfusion technique. Two of the prodrugs
      were able to significantly inhibit the uptake of glucose transporter (GluT1)
      mediated uptake of glucose, thereby demonstrating affinity to the transporter.
      Furthermore, the prodrugs were able to cross the BBB in a temperature-dependent
      manner, suggesting that the brain uptake of the prodrugs is carrier-mediated.

PMID- 19402666
TI  - Synthesis and biological characterization of B-ring amino analogues of potent
      benzothiadiazine hepatitis C virus polymerase inhibitors.
AB  - Benzothiadiazine inhibitors of the HCV NS5B RNA-dependent RNA polymerase are an
      important class of non-nucleoside inhibitors that have received considerable
      attention in the search for novel HCV therapeutics. Research in our laboratories
      has identified a novel series of tetracyclic benzothiadiazine inhibitors of HCV
      polymerase bearing a benzylamino substituent on the B-ring. Compounds in this
      series exhibit low-nanomolar activities in both genotypes 1a and 1b polymerase
      inhibition assays and subgenomic replicon assays. Optimization of pharmacokinetic
      properties in rat led to compound 30, which has good oral bioavailability (F =
      56%) and a favorable tissue distribution drug profile, with high liver to plasma
      ratios. Compound 30 is a potent inhibitor in replicon assays, with EC(50) values
      of 10 and 6 nM against genotypes 1a and 1b, respectively.

PMID- 19402665
TI  - Rhodamine inhibitors of P-glycoprotein: an amide/thioamide "switch" for ATPase
      activity.
AB  - We have examined 46 tetramethylrosamine/rhodamine derivatives with structural
      diversity in the heteroatom of the xanthylium core, the amino substituents of the
      3- and 6-positions, and the alkyl, aryl, or heteroaryl group at the 9
      substituent. These compounds were examined for affinity and ATPase stimulation in
      isolated MDR3 CL P-gp and human P-gp-His(10), for their ability to promote uptake
      of calcein AM and vinblastine in multidrug-resistant MDCKII-MDR1 cells, and for
      transport in monolayers of MDCKII-MDR1 cells. Thioamide 31-S gave K(M) of 0.087
      microM in human P-gp. Small changes in structure among this set of compounds
      affected affinity as well as transport rate (or flux) even though all derivatives
      examined were substrates for P-gp. With isolated protein, tertiary amide groups
      dictate high affinity and high stimulation while tertiary thioamide groups give
      high affinity and inhibition of ATPase activity. In MDCKII-MDR1 cells, the
      tertiary thioamide-containing derivatives promote uptake of calcein AM and have
      very slow passive, absorptive, and secretory rates of transport relative to
      transport rates for tertiary amide-containing derivatives. Thioamide 31-S
      promoted uptake of calcein AM and inhibited efflux of vinblastine with IC(50)'s
      of approximately 2 microM in MDCKII-MDR1 cells.

PMID- 19402667
TI  - Synthesis and biophysical characterization of chlorambucil anticancer ether lipid
      prodrugs.
AB  - The synthesis and biophysical characterization of four prodrug ether phospholipid
      conjugates are described. The lipids are prepared from the anticancer drug
      chlorambucil and have C16 and C18 ether chains with phosphatidylcholine or
      phosphatidylglycerol headgroups. All four prodrugs have the ability to form
      unilamellar liposomes (86-125 nm) and are hydrolyzed by phospholipase A(2),
      resulting in chlorambucil release. Liposomal formulations of prodrug lipids
      displayed cytotoxicity toward HT-29, MT-3, and ES-2 cancer cell lines in the
      presence of phospholipase A(2), with IC(50) values in the 8-36 microM range.

PMID- 19402668
TI  - Synthesis and structure-activity relationship of griseofulvin analogues as
      inhibitors of centrosomal clustering in cancer cells.
AB  - Griseofulvin was identified as an inhibitor of centrosomal clustering in a
      recently developed assay. Centrosomal clustering is an important cellular event
      that enables bipolar mitosis for cancer cell lines harboring supernumerary
      centrosomes. We report herein the synthesis and SAR of 34 griseofulvin analogues
      as inhibitors of centrosomal clustering. The variations in the griseofulvin
      structure cover five positions, namely the 4, 5, 2', 3', and 4' positions.
      Modification of the 4 and 5 positions affords inactive molecules. The enol ether
      must be at the 2' position, and the 4' position needs to be sp(2) hybridized. The
      most active analogues were the 2'-benzyloxy and 2'-(4-methylbenzyloxy) analogues
      as well as the oxime of the former with a 25-fold increase of activity compared
      to griseofulvin. Comparison of the results obtained in this work with prior
      reported growth inhibition data for dermatophytic fungi showed both similarities
      and differences.

PMID- 19402669
TI  - Isomer resolution by micelle-assisted diffusion-ordered spectroscopy.
AB  - Diffusion-ordered NMR spectroscopy ("DOSY") is a useful tool for the
      identification of mixture components. In its basic form it relies on simple
      differences in hydrodynamic radius to distinguish between different species. This
      can be very effective where species have significantly different molecular sizes,
      but generally fails for isomeric species. The use of surfactant co-solutes can
      allow isomeric species to be distinguished by virtue of their different degrees
      of interaction with micelles or reversed micelles. The use of micelle-assisted
      DOSY to resolve the NMR spectra of isomers is illustrated for the case of the
      three dihydroxybenzenes (catechol, resorcinol, and hydroquinone) in aqueous
      solution containing sodium dodecyl sulfate micelles, and in chloroform solution
      containing AOT reversed micelles.

PMID- 19402670
TI  - Rearrangements of [C(6)H(7)Si](+) cations. A radiochemical and quantum chemical
      study.
AB  - Nucleogenic cations were formed by beta-decay of phenylsilane tritiated at ortho-
      and para-positions of the benzene ring as well as at the silyl group and the
      products of their reactions with methyl tert-butyl ether were analyzed by
      radiochromatography. We found that the o-silatolyl cation was isomerized into the
      silabenzyl cation while the p-silatolyl cation was not. Furthermore, the
      silabenzyl cation was not converted into other isomers. The potential energy
      surface of the C(6)H(7)Si(+) system was constructed by B3LYP and MP2 methods
      using an aug-cc-pVDZ basis set. Theory predicts the low barrier for o-silatolyl
      silabenzyl isomerization but high barriers for hydride shifts in the ring from
      para to meta- to ortho-isomers. It seems that nascent nucleogenic ions have
      enough internal energy to overcome the ortho-to-benzyl barrier but not enough to
      cross over the hydride-shift barriers. Theory also confirms that the
      isomerization of the silabenzyl cation to the [C(6)H(6).SiH](+) complex takes
      place in one step with a 62 kcal mol(-1) barrier, whereas that to either the
      global minimum [C(6)H(7).Si](+) or the silatropylium ion involves multisteps with
      69-80 kcal/mol barriers. In addition, we find that the barrier of interconversion
      between the [C(6)H(6).SiH](+) complex and one of the low-lying [C(6)H(7).Si](+)
      complexes is only 29 kcal/mol.

PMID- 19402671
TI  - Quantification of heparan sulfate disaccharides using ion-pairing reversed-phase
      microflow high-performance liquid chromatography with electrospray ionization
      trap mass spectrometry.
AB  - The glycosaminoglycan (GAG) family of biomacromolecules is composed acidic and
      linear chains of repeating disaccharide units. Quantitative disaccharide
      composition analysis is essential for the study and characterization of GAGs.
      Heparan sulfate and heparin consist of multiple disaccharide units and can be
      well-separated by ion-pairing reversed-phase microflow high-performance liquid
      chromatography (IPRP-Mf-HPLC). Each disaccharide can be detected and its mass
      confirmed by electrospray ionization mass spectrometry (ESI-MS). Isotopically
      enriched disaccharides were prepared chemoenzymatically from a uniformly
      (13)C,(15)N-labeled N-acetylheparosan (-GlcA(1-->4)GlcNAc-) obtained from the
      fermentation of E. coli K5. These isotopically enriched disaccharides have
      identical HPLC retention times and mass spectra as their unlabeled counterparts
      and were used in liquid chromatography-mass spectrometry (LC-MS) as internal
      standards. The ratio of intensities between each pair of enriched and nonenriched
      disaccharides showed a linear relationship as a function of concentration. With
      the use of these calibration curves, the amount of each disaccharide (> or = 2
      ng/disaccharide) could be quantified in four heparan sulfate samples analyzed by
      this method.

PMID- 19402673
TI  - Fully automated analysis of beta-lactams in bovine milk by online solid phase
      extraction-liquid chromatography-electrospray-tandem mass spectrometry.
AB  - A fully automated method for the detection of beta-lactam antibiotics, including
      six penicillins (amoxicillin, ampicillin, cloxacillin, dicloxacillin, oxacillin,
      and penicillin G) and four cephalosporins (cefazolin, ceftiofur, cefoperazone,
      and cefalexin) in bovine milk samples has been developed. The outlined method is
      based on online solid-phase extraction-liquid chromatography/electrospray-tandem
      mass spectrometry (SPE-LC/ESI-MS-MS). Target compounds were concentrated from 500
      microL of centrifuged milk samples using an online SPE procedure with C18 HD
      cartridges. Target analytes were eluted with a gradient mobile phase (water +
      0.1% formic acid/methanol + 0.1% formic acid) at a flow rate of 0.7 mL/min.
      Chromatographic separation was achieved within 10 min using a C-12 reversed phase
      analytical column. For unequivocal identification and confirmation, two multiple
      reaction monitoring (MRM) transitions were acquired for each analyte in the
      positive electrospray ionization mode (ESI(+)). Method limits of detection (LODs)
      in milk were well below the maximum residue limits (MRLs) set by the European
      Union for all compounds. Limits of quantification in milk were between 0.09 ng/mL
      and 1.44 ng/mL. The developed method was validated according to EU's
      requirements, and accuracy results ranged from 80 to 116%. Finally, the method
      was applied to the analysis of twenty real samples previously screened by the
      inhibition of microbial growth test Eclipse 100. This new developed method offers
      high sensitivity and accuracy of results, minimum sample pre-treatment, and uses
      for the first time an automated online SPE offering a high throughput analysis.
      Because of all these characteristics, the proposed method is applicable and could
      be deemed necessary within the field of food control and safety.

PMID- 19402672
TI  - Simultaneous electrochemical monitoring of metabolites related to the xanthine
      oxidase pathway using a grinded carbon electrode.
AB  - Using a mechanically grinded pyrolytic graphite electrode in edge orientation, a
      sensitive electrochemical method was developed for simultaneous determination of
      uric acid (UA), xanthine (XAN), hypoxanthine (HYP) (products of purine catabolism
      in human), allopurinol (ALO), and oxypurinol (OXY) (a drug used in treatment of
      purine catabolism disorders and its metabolite, respectively). It is demonstrated
      that differential pulse voltammetry in connection with this electrode can serve
      as a simple and efficient tool for monitoring transformation of purine
      catabolites (HYP --> XAN --> UA) catalyzed by xanthine oxidase (XO) as well as
      inhibition of this pathway by ALO being enzymatically converted to OXY. Our
      protocol is based on direct electrochemical measurement of oxidation peaks for
      each of the substances during in vitro reactions in a single detection step by
      the same electrode system. In addition, we show that the proposed electrochemical
      technique can be applied to parallel detection of metabolites involved in the XO
      pathway excreted in urine without any pretreatment of the clinical samples.

PMID- 19402674
TI  - Monoterpene glucosides from Paeonia lactiflora.
AB  - Four new "cage-like" monoterpene glucosides (1-4) were isolated from Paeonia
      lactiflora. The structures of these compounds were established by spectroscopic
      methods, mainly 1D and 2D NMR, and mass spectrometric analysis. Compound 4
      exhibited moderate cell-protective activity against hydrogen peroxide-induced
      PC12 cell damage.

PMID- 19402675
TI  - Palladium-catalyzed decarboxylative coupling of allylic alkynoates with arynes.
AB  - A novel and selective protocol for the synthesis of 1-allyl-2-ethynylbenzenes has
      been developed by palladium-catalyzed decarboxylative coupling of allylic
      alkynoates with arynes. This new route allows for both sp-sp(2) and sp(2)-sp(3)
      couplings of allylic alkynoates with arynes in one pot involving a
      decarboxylation process.

PMID- 19402676
TI  - Isolable zwitterionic pyridinio-semiquinone pi-radicals. Mild and efficient
      single-step access to stable radicals.
AB  - A rational design based on the proton-coupled electron transfer (PCET) concept
      allows us to structurally characterize for the first time isolable, air- and
      moisture-stable semiquinone radicals in a zwitterionic neutral form. The presence
      of an alkoxy and the bulky pyridinio substituents causes only a minor
      perturbation of either the redox potentials or the spectral UV-vis
      characteristics of the semiquinone core but significantly stabilizes the new
      radicals.

PMID- 19402677
TI  - Quantitative characterization of solid epoxy resins using comprehensive two
      dimensional liquid chromatography coupled with electrospray ionization-time of
      flight mass spectrometry.
AB  - A comprehensive multidimensional liquid chromatography system coupled to
      Electrospray Ionization-Mass Spectrometry (LCxLC-ESI-MS) was developed for
      detailed characterization and quantitation of solid epoxy resin components. The
      two orthogonal modes of separation selected were size exclusion chromatography
      (SEC) in the first dimension and liquid chromatography at critical conditions
      (LCCC) in the second dimension. Different components present in the solid epoxy
      resins were separated and quantitated for the first time based on the functional
      groups and molecular weight heterogeneity. Coupling LCxLC separations with mass
      spectrometry enabled the identification of components resolved in the two
      dimensional space. Several different functional group families of compounds were
      separated and identified, including epoxy-epoxy and epoxy-alpha-glycol functional
      oligomers, and their individual molecular weight ranges were determined.
      Repeatability obtained ranged from 0.5% for the main product to 21% for oligomers
      at the 0.4% concentration level.

PMID- 19402678
TI  - Differential pulse voltammetry for ion transfer at liquid membranes with two
      polarized interfaces.
AB  - A simple analytical expression for the response of the double-pulse technique
      differential pulse voltammetry (DPV) corresponding to ion transfer processes in
      systems with two liquid/liquid polarizable interfaces has been deduced. This
      expression predicts lower and wider curves than those obtained with a membrane
      system with a single polarizable interface. Moreover, the peak potential of these
      systems is shifted 13 mV from the half-wave membrane potential. We have applied
      this expression to study the ion transfer of drugs with different pharmacological
      activities (verapamil, clomipramine, tacrine, and imipramine), at a solvent
      polymeric membrane ion sensor.

PMID- 19402679
TI  - A concise route to branched erythrono-gamma-lactones. Synthesis of the leaf
      closing substance potassium (+/-)-(2R,3R)-2,3,4-trihydroxy-2-methylbutanoate.
AB  - A series of 1,2-dioxanes 3 were ring-opened with Co(SALEN)(2) to furnish lactol
      regioisomers 4 and 5 (86-99% yield). The lactols were oxidized to gamma-lactones
      8 and 9 (72-96% yield) and deprotected to afford the 2-C- and 3-C-alkyl and aryl
      branched erythrono-gamma-lactones 1, 6, and 7 (65-94% yield), including the
      natural plant lactone (+/-)-2-C-d-methylerythrono-1,4-lactone 1. The latter
      compound was treated with aqueous potassium hydroxide to afford potassium (+/-)
      (2R,3R)-2,3,4-trihydroxy-2-methylbutanoate 2, which is a leaf-closing substance
      of Leucaena leucocephalam.

PMID- 19402680
TI  - Linear and branched perfluorooctane sulfonate isomers in technical product and
      environmental samples by in-port derivatization-gas chromatography-mass
      spectrometry.
AB  - Perfluorooctane sulfonate (PFOS) is found globally as an environmental
      contaminant and is highly bioaccumulative in exposed biota including humans.
      However, there is a dearth of environmental information on the isomeric profile
      of PFOS, especially in biological samples, which requires suitable analysis
      methods for the identification and quantification of ultratrace amounts. In the
      present study, a novel method was developed that incorporates clean up by solid
      phase extraction (SPE) WAX cartridges and in-port derivatization-gas
      chromatography-mass spectrometry (GC/MS) to identify and quantitatively determine
      linear PFOS (L-PFOS) and branched (monotrifluoromethyl and bistrifluoromethyl)
      isomers in PFOS technical product and in environmentally relevant biological
      samples. Tetrabutylammonium hydroxide (TBAH) was used for derivatization via an
      in situ pyrolytic alkylation reaction that occurred in the GC injector and
      generated butyl PFOS isomer derivatives. In addition to L-PFOS, ten branched PFOS
      isomers were identified in the technical product. The environmental relevance of
      branched PFOS isomers in addition to L-PFOS was evidenced by the presence of six
      branched and L-PFOS in representative herring gull and double-crested cormorant
      egg, and polar bear liver and plasma samples from the Great Lakes and Arctic,
      respectively. For all PFOS isomers in the technical product and biota samples the
      method demonstrated high sensitivity with the limit of detection (LOD) ranging
      from 0.05 to 0.25 ng/mL, with exception of L-PFOS where the LOD was 1.46 ng/mL.
      For the biotic samples, the method detection limits (MDLs) were slightly higher
      than the LODs and ranged from 0.09 to 0.46 ng/g wet weight (w.w.) with exception
      of L-PFOS (MDL = 6.87 ng/g w.w.).

PMID- 19402681
TI  - Amination of allylic alcohols in water at room temperature.
AB  - The "trick" to carrying out regiocontrolled aminations of allylic alcohols in
      water as the only medium is use of a nanomicelle's interior as the organic
      reaction solvent. When HCO(2)Me is present, along with the proper base and source
      of catalytic Pd, allylic amines are cleanly formed at room temperature.

PMID- 19402682
TI  - Synthesis, microwave spectrum, and conformational equilibrium of propa-1,2
      dienethiol (H(2)=C=CHSH).
AB  - The first synthesis of the kinetically unstable compound propa-1,2-dienethiol
      (allenethiol; H(2)CCCHSH) is reported. Its microwave spectrum has been studied in
      the 41.5-80 GHz spectral range. The spectra of two rotameric forms have been
      assigned. The C-C-S-H chain of atoms is synperiplanar (0 degrees ) in one of the
      conformers. This dihedral angle is anticlinal in the second rotamer forming an
      angle of 140(5) degrees in the second form. The synperiplanar conformer is found
      to be 1.0(6) kJ/mol more stable than the anticlinal rotamer. The microwave study
      has been augmented by quantum chemical calculations at the MP2/aug-cc-pVTZ and
      B3LYP/6-311++G** levels of theory. The predictions of these two theoretical
      methods are in excellent agreement with the experimental findings.

PMID- 19402684
TI  - Boundary slip study on hydrophilic, hydrophobic, and superhydrophobic surfaces
      with dynamic atomic force microscopy.
AB  - Slip length has been measured using the dynamic atomic force microscopy (AFM)
      method. Unlike the contact AFM method, the sample surface approaches an
      oscillating sphere with a very low velocity in the dynamic AFM method. During
      this process, the amplitude and phase shift data are recorded to calculate the
      hydrodynamic damping coefficient, which is then used to obtain slip length. In
      this study, a glass sphere with a large radius was glued to the end of an AFM
      cantilever to measure the slip length on rough surfaces. Experimental results for
      hydrophilic, hydrophobic, and superhydrophobic surfaces show that the
      hydrodynamic damping coefficient decreases from the hydrophilic surface to the
      hydrophobic surface and from the hydrophobic one to the superhydrophobic one. The
      slip lengths obtained on the hydrophobic and superhydrophobic surfaces are 43 and
      236 nm, respectively, which indicates increasing boundary slip from the
      hydrophobic surface to the superhydrophobic one.

PMID- 19402683
TI  - Gas-phase intramolecular phosphate shift in phosphotyrosine-containing peptide
      monoanions.
AB  - Phosphotyrosine-containing peptide monoanions [M-H](-) exhibit extensive neutral
      loss of phosphoric acid (98 Da) upon quadrupole time-of-flight and ion-trap
      collision-induced dissociation (CID). In contrast, a neutral loss of
      metaphosphoric acid HPO(3) (80 Da) is negligible from the deprotonated
      phosphotyrosine peptides. The efficient H(3)PO(4) release is unexpected, given
      the structure of phosphotyrosine. Our study reveals that the abundant [M-H-98](-)
      product ions of pTyr-peptides are not a result of consecutive losses of HPO(3)
      and H(2)O but, rather, are induced by an intramolecular interaction of the
      phosphotyrosine phosphate with deprotonated peptide functions such as hydroxyl,
      carboxyl, and to a small extent, amide. As a result, an internal phosphotyrosine
      phosphate shift occurs, and the obtained phosphorylated functionalities undergo
      elimination of H(3)PO(4) to give rise to the [M-H-98](-) fragments. The mechanism
      proposed for the phosphoric acid neutral loss is based on extensive CID studies
      of Ala-substituted model phosphorylated peptides and oxygen-18 labeling. The
      proposed mechanistic pathway explains the fact that the pTyr phosphate transfer
      and the subsequent H(3)PO(4) neutral loss are not observed for multiply charged
      anions of pTyr-peptides. Monoanions of pSer-containing peptides undergo the
      intramolecular phosphate shift as well, although its efficiency is much lower
      compared to the aromatic phosphorylation sites. These observations facilitate
      correct identification of pSer-, pThr-, and pTyr-peptides in CID studies. This
      work demonstrates that the established phosphate-specific neutral loss
      fragmentation rules of protonated pTyr-peptides cannot be applied to the CID
      spectra of their [M-H](-) ions.

PMID- 19402686
TI  - Wettability-controllable super water- and moderately oil-repellent surface
      fabricated by wet chemical etching.
AB  - A facile fabrication method is presented for a super-repellent surface, in which
      a silicon wafer is etched with a wet chemical method and treated by a fluorinated
      self-assembled monolayer. This surface is composed of harshly rough
      nanostructures and highly dense nanoholes. The contact angle of both water and
      oil with the surface is larger than 150 degrees. The self-cleaning capability of
      the surface allows for the removal of sticky powders with glycerin droplet. Any
      desired part(s) of the super-repellent surface can be turned superamphiphilic by
      simply exposing the desired part(s) to ultraviolet light.

PMID- 19402685
TI  - Photoinduced electron transfer in porphyrin- and fullerene/porphyrin-based
      rotaxanes as studied by time-resolved EPR spectroscopy.
AB  - Photoinduced intramolecular electron-transfer (ET) and energy-transfer (EnT)
      processes in two rotaxanes, one containing both zinc porphyrin and C(60)
      fullerene moieties incorporated around the Cu(I) bisphenanthroline core [(ZnP)(2)
      Cu(I)(phen)(2)-C(60)] and a second complex lacking the fullerene [(ZnP)(2)
      Cu(I)(phen)(2)], were studied by time-resolved electron paramagnetic resonance
      (TREPR) spectroscopy at 9.5 GHz (X-band) combined with a selective
      photoexcitation of the rotaxane moieties. The experiments were carried out in
      isotropic toluene and ethanol and in anisotropic nematic liquid-crystal (E-7)
      media over a wide range of temperatures corresponding to the different states of
      the solvents. The TREPR results are compared with those obtained previously by
      optical methods in dichloromethane at room temperature. It is demonstrated that
      the efficiencies and pathways of the light-driven ET and EnT processes in both
      rotaxanes strongly depend on the properties of their microenvironment, resulting
      in the formation of distinct charge-separated states under different experimental
      conditions. The complementary results revealed by the optical and TREPR
      techniques are attributed to the relatively high conformational mobility of the
      mechanically interlocked rotaxane systems. Because of the solute-solvent
      interactions, the rotaxanes are able to change conformation in different
      microenvironments, which affects the parameters of the photoinduced processes
      occurring in these systems.

PMID- 19402687
TI  - Bioisosteric similarity of molecules based on structural alignment and observed
      chemical replacements in drugs.
AB  - The algorithmic concept used to assess the evolutionary relationship between
      protein sequences was adopted to the comparison of drug-like compounds. For this
      purpose, we have developed a method that uses the SMILES representation of the
      molecules to perform the corresponding pairwise alignment. The necessary exchange
      matrix was generated in an automated procedure that reflects the frequencies of
      chemical replacements in pharmaceutical substances. From the resulting alignment,
      the relationship between two molecules is computed as so-called bioisosteric
      similarity. This measure was used to perform virtual screening in several
      publicly available substance databases. We observed that databases containing
      drug-like compounds throughout showed higher bioisosteric similarities to the
      query compound than our reference set of confirmed nondrugs. Likewise, most
      actual drugs within a class show a higher bioisosteric similarity than the large
      background of other substances. The compounds obtained as highest ranking hits
      from the lead-like subset of the ZINC library showed distinct differences in
      comparison with corresponding results from a fingerprint-based similarity search,
      as well as the FTrees method. In particular the kind of chemical replacements as
      well as the conservation of substructures strongly reflect the underlying
      bioisosteric exchanges. Moreover, the bioisosteric similarity was used to assess
      the chemical diversity of the utilized drug classes and to compute the "average"
      molecule within the respective class.

PMID- 19402688
TI  - Self-assembling chiral gelators for fluorinated media.
AB  - Formulations involving partially and fully fluorinated media represent a
      technological challenge given the lipophobic and hydrophobic nature of such
      liquids. The identification of self-associating materials with which to control
      the viscosity and solubilizing characteristics of fluorinated solvents is a
      particularly interesting area of research. It is shown here that the presence of
      the stereogenic centers inherent in a family of bis-(alpha,beta-dihydroxy ester)s
      is an essential requirement for the thermoreversible gelation of mixtures of
      partially fluorinated liquids 2H,3H-perfluoropentane (HPFP) and 1H,1H
      heptafluorobutanol (HFB). Gelation is driven by hydrogen bonding, which induces a
      nonpreferred conformation around the bis-(alpha,beta-dihydroxy ester) structural
      motif. An analysis of the melting temperature yields an enthalpy of melting that
      is consistent with three to four hydrogen bonds, commensurate with the end-group
      structure of the gelator. Small-angle neutron scattering demonstrated the
      existence of the common fibrillar structures whose dimensions showed no obvious
      correlation with the molecular structure of the gelator.

PMID- 19402689
TI  - Synthesis and characterization of self-assembled polyaniline nanotubes/silica
      nanocomposites.
AB  - Self-assembled semiconducting, paramagnetic polyaniline nanotubes have been
      synthesized by the oxidative polymerization of aniline with ammonium
      peroxydisulfate in aqueous medium in the presence of colloidal silica particles
      of an average diameter approximately 12 nm, without added acid. The electrical
      conductivity of polyaniline nanotubes/silica nanocomposites is in the range (3.3
      4.0)x10(-3) S cm(-1). The presence of paramagnetic polaronic emeraldine salt form
      of polyaniline and phenazine units in nanocomposites was proved by FTIR, Raman,
      and EPR spectroscopies. The influence of the initial silica/aniline weight ratio
      on the morphology of polyaniline/silica nanocomposites was studied by scanning
      and transmission electron microscopies. Nanocomposites synthesized by using the
      initial weight ratio silica/aniline<or=0.2 contain polyaniline nanotubes which
      have a typical outer diameter of 100-250 nm and an inner diameter of 10-80 nm,
      and nanorods with a diameter of 60-100 nm, accompanied with polyaniline/silica
      nanogranules, while the nanocomposite synthesized at weight ratio silica/aniline
      approximately 2 contains polyaniline/silica nanogranules with an average diameter
      of 35-70 nm. The evolution of molecular and supramolecular structure of
      polyaniline in the presence of colloidal silica is discussed.

PMID- 19402690
TI  - On the line tension of curved boundary layers. I. boundary thermodynamics.
AB  - We present a formally exact thermodynamic treatment of curved boundary layers.
      Specifically, we extend the boundary layer analysis of Mandell and Reiss [ J.
      Stat. Phys. 1975 , 13 , 107 ] for a spherical cavity located within a uniform
      bulk fluid to the case of a cavity intersecting a hard, structureless wall. We
      derive various expressions for the line tension of an intersecting cavity, all of
      which can be evaluated for a hard-sphere fluid using existing versions of scaled
      particle theory. Since the analysis is similar to the standard approach for
      describing curved interfacial layers, several boundary analogues to conventional
      interfacial relations appear. In some instances, we obtain results that
      apparently have not yet been derived either for boundary layers or for their
      parallel relations in interfacial thermodynamics. Several results offer
      interesting insights into the behavior of the line tension of a cavity when the
      cavity approaches macroscopic sizes or in the specific limit where the cavity no
      longer intersects the wall.

PMID- 19402691
TI  - Dynamics and structure of Ln(III)-aqua ions: a comparative molecular dynamics
      study using ab initio based flexible and polarizable model potentials.
AB  - Aqueous solutions of a light (Nd3+), a middle (Gd3+), and a heavy (Yb3+)
      lanthanide ion were studied using ab initio based flexible and polarizable
      analytical potentials in classical molecular dynamics simulations to describe
      their thermodynamic, structural, and dynamic features. To avoid the spurious
      demise of O-H bonds, it was necessary to reparametrize an existing water model,
      which resulted in an improved description of pure water. The good agreement of
      the results from the simulations with the experimental hydration enthalpies, the
      Ln(III)-water radial distribution functions, and the water-exchange rates
      validated the potentials, though the r(Ln-Ow) distances were 6% longer than the
      experimentally determined values. A nona-coordinated state was found for Nd3+ in
      95% of the simulation, with a tricapped trigonal prism (TCTP) geometry; the
      corresponding water-exchange mechanism was found to be of dissociative
      interchange (Id) character through a short-lived octa-coordinated transition
      state in a square antiprism (SQA) geometry. An octa-coordinated state in SQA
      geometry was found for Yb3+ in 99% of the simulation, and the observed exchange
      events exhibited characteristics of an interchange (I) mechanism. For Gd3+ an
      equilibrium was observed between 8-fold SQA and 9-fold TCTP coordinated states
      that was maintained by the frequent exchange of a water molecule from the first
      hydration shell with the bulk, thus producing significant deviations from the
      ideal geometries, and a fast exchange rate. Though strong water-water
      interactions prevented a full alignment of the dipoles to the ion's electric
      field, the screening was found large enough as to limit its range to 5 A; water
      molecules further apart from the ion were found to have the same dipole as the
      molecules in the bulk, and a random orientation. The interplay among the water
      ion and the water-water interactions determined the different coordination
      numbers and the different dynamics of the water exchange in the first hydration
      shell for each ion.

PMID- 19402692
TI  - Obtaining kinetic information from the chain-length distribution of polymers
      produced by RAFT.
AB  - We describe a simple model for the kinetics and chain-length distribution of
      polymers made by living radical techniques. Living radical methods give good
      control over the molecular weight of a linear polymer by capping the growing end
      and forming a dormant chain. The polymer is predominantly capped, and
      occasionally decaps to form a radical that propagates for a short period before
      recapping. Our model uses this mechanism to describe the chain-length
      distribution of polymers made by living radical methods. We focus on oligomers
      made by reversible addition-fragmentation chain transfer (RAFT) polymerization as
      model systems. Our model can determine optimal reaction conditions for desired
      polymer properties and test hypotheses about reaction schemes by using only two
      parameters, with each parameter related to the kinetics. The first parameter is
      the mean number of monomers added when a chain decaps. A broad distribution
      results if many monomers are added upon decapping. The second parameter is the
      mean number of times a polymer decaps. Many decapping events indicate high
      monomer conversion. Our model gives kinetic information by directly fitting to an
      experimental chain-length distribution, which is the reverse of other kinetic
      models that generate the distribution from rate coefficients. Our approach has
      also the advantage of being simpler than previously published kinetic schemes,
      which use many rate coefficients as inputs. Our model was tested against three
      monomers (acrylic acid, butyl acrylate, and styrene) and two RAFT agents. In each
      case, we successfully describe the chain-length distribution, and give
      information about the kinetics, especially the probability of propagation versus
      deactivation by the RAFT mechanism. This excellent agreement with a priori
      expectations and quantum calculations makes our model a powerful tool for
      predicting the structure of polymers obtained by living radical polymerization.

PMID- 19402693
TI  - High pressure Diels-Alder approach to hydroxy-substituted 6a-cyano-tetrahydro-6H
      benzo[c]chromen-6-ones: a route to delta(6)-cis-cannabidiol.
AB  - Diels-Alder cycloaddition reactions of 3-cyanocoumarin, hydroxy-substituted 3
      cyanocoumarins and mesyl-substituted 3-cyano-coumarins with methyl-1,3-butadienes
      carried out under high pressure (11 kbar) are reported. Activation by high
      pressure allows these reactions to proceed satisfactorily under mild conditions
      to produce 6a-cyano-hydroxy- and 6a-cyano-mesyl-tetrahydro-6H-benzo[c]chromen-6
      ones in moderate to excellent yield. The synthesis of cis-1-hydroxy-9-methyl-3
      pentyl-6a,7,10,10a-tetrahydro-benzo[c]chromen-6-one as precursor of Delta(6)-3,4
      cis-cannabidiol (Delta(6)-cis-CBD) and Delta(8)-cis-tetrahydrocannabinol
      (Delta(8)-cis-THC) is outlined.

PMID- 19402694
TI  - Synthesis of hyaluronic acid oligomers using chemoselective and one-pot
      strategies.
AB  - An efficient synthetic strategy toward a hyaluronic acid (HA) tri-, penta-, and
      heptamer having a glucosamine-reducing end is reported. The synthesis is based on
      a glucuronate ester thioglycoside and a trifluoro-N-phenylimidate glucosamine
      building block. The HA-fragments are synthesized using an S-phenyl GlcN-GluA
      building block through a combination of chemoselective and one-pot condensation
      strategies.

PMID- 19402695
TI  - P(i-PrNCH2CH2)3N: efficient catalyst for synthesizing beta-hydroxyesters and
      alpha,beta-unsaturated esters using alpha-trimethylsilylethylacetate (TMSEA).
AB  - We present an efficient synthesis of beta-hydroxyesters and alpha,beta
      unsaturated esters via activation of the silicon-carbon bond of alpha
      trimethylsilylethylacetate using catalytic amounts of the commercially available
      P(i-PrNCH(2)CH(2))(3)N 1a. Selectivity for either of these two products can be
      achieved simply by altering the catalyst loading and reaction temperature to
      afford addition or stereoselective condensation. This method is mild and
      tolerates a wide array of functional groups.

PMID- 19402697
TI  - Synthesis and chemistry of 4,5-dihydrothieno[3,2-b]pyrrol-6-one--a heteroindoxyl.
AB  - Flash vacuum pyrolysis (FVP) of 2-acetyl-3-azidothiophene gives 3
      methylthieno[3,2-c]isoxazole as the major product at a furnace temperature of 350
      degrees C whereas at temperatures above 550 degrees C the new heteroindoxyl 4,5
      dihydrothieno[3,2-b]pyrrol-6-one is exclusively formed. The heteroindoxyl exists
      predominantly as the keto tautomer. It is O-protonated by TFA, N-acetylated by
      acetic anhydride, N-nitrosated by nitrous acid, and provides an N-methylene
      Meldrum's acid derivative on treatment with methoxymethylene Meldrum's acid.
      Reactions of 4,5-dihydrothieno[3,2-b]pyrrol-6-one with diazonium salts, with
      isatin, and with dimethyl acetylenedicarboxylate take place at the methylene
      position to provide a hydrazone, an indirubin analogue, and a succinate
      derivative, respectively. Oxidation of 4,5-dihydrothieno[3,2-b]pyrrol-6-one gives
      a heteroindigotin, which shows a hypsochromic shift in the UV spectrum, relative
      to indigotin itself.

PMID- 19402696
TI  - Cu(I)-catalyzed C-H alpha-amination of aryl ketones: direct synthesis of
      imidazolinones.
AB  - This paper describes an alpha-amination process of aryl ketones using CuCl as
      catalyst and di-tert-butyldiaziridinone as the nitrogen source. A variety of
      imidazolinone derivatives are prepared in moderate yields under mild conditions.
      A possible catalytic cycle is proposed for this reaction.

PMID- 19402698
TI  - Synthesis of 2,5-dihydrofuran-fused quinones from ether-tethered diiododiyne.
AB  - Biologically interesting 2,5-dihydrofuran-fused quinones were synthesized via the
      ruthenium-catalyzed [2 + 2 + 2] cycloaddition of an ether-tethered diiododiyne
      with alkynes, copper-catalyzed Ullmann coupling of the resultant fused p
      diiodobenzenes with methanol or allyl alcohol, and subsequent oxidation of phenol
      derivatives. The double Claisen rearrangement of the bis(allyl) ether product
      furnished a diallylhydroquinone derivative, which underwent iron-catalyzed
      oxidation, ring-closing metathesis, and dehydrogenation to deliver 1,3
      dihydronaphtho[2,3-c]furan-4,9-dione.

PMID- 19402699
TI  - Highly regio- and stereoselective addition of organolithium reagents to extended
      conjugate amides using (S,S)-(+)-pseudoephedrine as chiral auxiliary.
AB  - The conjugate addition of organolithium reagents to polyunsaturated conjugate
      amides containing (S,S)-(+)-pseudoephedrine as chiral auxiliary has been studied
      in detail. The reaction proceeded with good 1,4-selectivity and excellent
      stereoselectivity, affording the corresponding addition products with good yields
      and as highly diastereoenriched isomers. Removal of the chiral auxiliary by
      reduction or hydrolysis has allowed the preparation of polyfunctionalized chiral
      building blocks incorporating an alkene moiety suitable for further
      transformations.

PMID- 19402701
TI  - Metal-Bronsted acid cooperative catalysis for asymmetric reductive amination.
AB  - Direct reductive amination of a wide range of ketones has been accomplished by
      the cooperative catalysis of an Ir(III)-diamine complex and a chiral phosphoric
      acid or its conjugate base.

PMID- 19402700
TI  - Pattern and temporal sequence of sulfation of CCR5 N-terminal peptides by
      tyrosylprotein sulfotransferase-2: an assessment of the effects of N-terminal
      residues.
AB  - CC chemokine receptor 5 (CCR5) is the receptor for several inflammatory
      chemokines and is a coreceptor for HIV-1. Posttranslational sulfation of
      tyrosines in the N-terminal regions of chemokine receptors has been shown to be
      important in the binding affinity for chemokine ligands. In addition, sulfation
      of CCR5 is crucial for mediating interactions with HIV-1 envelope protein gp120.
      The major sulfation pathway for peptides derived from the N-terminal domains of
      CCR5 and CCR8 and variations of the peptides were determined by in vitro
      enzymatic sulfation by tyrosylprotein sulfotranferase-2 (TPST-2), subsequent
      separation of products by RP-HPLC, and mass spectrometry analysis. It was found
      that the patterns of sulfation and the rates of sulfation for CCR5 and CCR8
      depend on the number of amino acids N-terminal of Tyr-3. Results herein address
      previous seemingly contradictory studies and delineate the temporal sulfation of
      N-terminal chemokine receptor peptides.

PMID- 19402702
TI  - On the origin of the cobalt particle size effects in Fischer-Tropsch catalysis.
AB  - The effects of metal particle size in catalysis are of prime scientific and
      industrial importance and call for a better understanding. In this paper the
      origin of the cobalt particle size effects in Fischer-Tropsch (FT) catalysis was
      studied. Steady-State Isotopic Transient Kinetic Analysis (SSITKA) was applied to
      provide surface residence times and coverages of reaction intermediates as a
      function of Co particle size (2.6-16 nm). For carbon nanofiber supported cobalt
      catalysts at 210 degrees C and H(2)/CO = 10 v/v, it appeared that the surface
      residence times of reversibly bonded CH(x) and OH(x) intermediates increased,
      whereas that of CO decreased for small (<6 nm) Co particles. A higher coverage of
      irreversibly bonded CO was found for small Co particles that was ascribed to a
      larger fraction of low-coordinated surface sites. The coverages and residence
      times obtained from SSITKA were used to describe the surface-specific activity
      (TOF) quantitatively and the CH(4) selectivity qualitatively as a function of Co
      particle size for the FT reaction (220 degrees C, H(2)/CO = 2). The lower TOF of
      Co particles <6 nm is caused by both blocking of edge/corner sites and a lower
      intrinsic activity at the small terraces. The higher methane selectivity of small
      Co particles is mainly brought about by their higher hydrogen coverages.

PMID- 19402703
TI  - Crystal structure of a new cyan fluorescent protein and its hue-shifted variants.
AB  - Green fluorescent protein (GFP) based techniques are well established in
      molecular biology; however, the detailed mechanism for the fine-tuning of
      fluorescent colors remains unclear. Here, we report the cloning and crystal
      structure of a new cyan-emitting GFP-like protein, KCy. We also developed a
      mutant protein with a high folding efficiency (KCy-G4219: lambda(abs) = 453 nm;
      lambda(em) = 486 nm). X-ray diffraction analysis revealed that the KCy
      chromophore is formed from an internal Ser62-Tyr63-Gly64 tripeptide. The serine
      residue at the first position of the chromophore-forming tripeptide has a short
      polar chain (-OH) that forms a noncovalent interaction with the His38 imidazole
      at a distance of 2.96 A. Substitution of His38 in KCy-G4219 with Gln (KCy-R1) or
      Leu residues resulted in a slight but significant red shift of the emission peak
      maximum from 486 to 492 or 496 nm, respectively. The crystal structure of KCy-R1
      determined at a resolution of 1.58 A showed that the noncovalent interaction
      between Ser62-OH and the substituted Gln38 occurred over a longer distance (3.07
      A) than that observed in the wild-type KCy. Such an interaction is absent in the
      Leu mutant, suggesting that this interaction is one of the key factors
      responsible for fine-tuning the emission peak maxima, which are affected by
      chromophore polarization. Moreover, the structural comparison suggests that an
      additional water molecule buried in the space between the Ala158 residue and the
      chromophore phenolate is also responsible for the chromophore polarization.

PMID- 19402704
TI  - Re(bpy)(CO)3CN as a probe of conformational flexibility in a photochemical
      ribonucleotide reductase.
AB  - Photochemical ribonucleotide reductases (photoRNRs) have been developed to study
      the proton-coupled electron transfer (PCET) mechanism of radical transport in
      Escherichia coli class I ribonucleotide reductase (RNR). The transport of the
      effective radical occurs along several conserved aromatic residues across two
      subunits: beta2((*)Y122 --> W48 --> Y356) --> alpha2(Y731 --> Y730 --> C439). The
      current model for RNR activity suggests that radical transport is strongly
      controlled by conformational gating. The C-terminal tail peptide (Y-betaC19) of
      beta2 is the binding determinant of beta2 to alpha2 and contains the redox active
      Y356 residue. A photoRNR has been generated synthetically by appending a
      Re(bpy)(CO)(3)CN ([Re]) photo-oxidant next to Y356 of the 20-mer peptide.
      Emission from the [Re] center dramatically increases upon peptide binding,
      serving as a probe for conformational dynamics and the protonation state of Y356.
      The diffusion coefficient of [Re]-Y-betaC19 has been measured (k(d1) = 6.1 x 10(
      7) cm(-1) s(-1)), along with the dissociation rate constant for the [Re]-Y
      betaC19-alpha2 complex (7000 s(-1) > k(off) > 400 s(-1)). Results from detailed
      time-resolved emission and absorption spectroscopy reveal biexponential kinetics,
      suggesting a large degree of conformational flexibility in the [Re]-Y-betaC19
      alpha2 complex that engenders partitioning of the N-terminus of the peptide into
      both bound and solvent-exposed fractions.

PMID- 19402705
TI  - Biotinylated glyco-functionalized quantum dots: synthesis, characterization, and
      cytotoxicity studies.
AB  - Quantum dots (QDs) containing surface carboxylic groups have been successfully
      modified using biotinylated glycopolymer and carbohydrate/biotin reagents via EDC
      coupling. The biotinylated glycopolymer was synthesized in controlled dimension
      via the reversible addition-fragmentation chain transfer (RAFT) polymerization of
      the three monomers containing biotin, sugar, and amine groups as pendent groups,
      respectively. The modified QDs were analyzed by dynamic light scattering and
      fluorescence spectrophotometry, and the data revealed no change in the physical
      properties of QDs after surface modification. Furthermore, the surface modified
      QDs showed excellent water solubility and colloidal stability. Subsequently, the
      availability of the biotin ligand on the surface of functionalized QDs was
      quantified using 4-hydroxyazobenzene 2-carboxylic acid (HABA)/avidin binding
      assay. Cell viability studies revealed that the cytotoxicity of QDs after surface
      functionalization is improved and that the biotinylated glycopolymer modified QDs
      showed an enhancement in biocompatibility as compared to that of the original
      QDs. The biotinylated glyco-functionalized quantum dots may act as new suitable
      fluorescent probes in biomedical applications.

PMID- 19402706
TI  - Genetic engineering of the S-layer protein SbpA of Lysinibacillus sphaericus CCM
      2177 for the generation of functionalized nanoarrays.
AB  - The mesophilic organism Lysinibacillus sphaericus CCM 2177 produces the surface
      (S)-layer protein SbpA, which after secretion completely covers the cell surface
      with a crystalline array exhibiting square lattice symmetry. Because of its
      excellent in vitro recrystallization properties on solid supports, SbpA
      represents a suitable candidate for genetically engineering to create a versatile
      self-assembly system for the development of a molecular construction kit for
      nanobiotechnological applications. The first goal of this study was to
      investigate the surface location of 3 different C-terminal amino acid positions
      within the S-layer lattice formed by SbpA. Therefore, three derivatives of SbpA
      were constructed, in which 90, 173, or 200 C-terminal amino acids were deleted,
      and the sequence encoding the short affinity tag Strep-tag II as well as a single
      cysteine residue were fused to their C-terminal end. Recrystallization studies of
      the rSbpA/STII/Cys fusion proteins indicated that C-terminal truncation and
      functionalization of the S-layer protein did not interfere with the self-assembly
      capability. Fluorescent labeling demonstrated that the orientation of the
      crystalline rSbpA(31-1178)/STII/Cys lattice on solid supports was the same, like
      the orientation of wild-type S-layer protein SbpA on the bacterial cell. In
      soluble and recrystallized rSbpA/STII/Cys fusion proteins, Strep-tag II was used
      for prescreening of the surface accessibility, whereas the thiol group of the end
      standing cysteine residue was exploited for site-directed chemical linkage of
      differently sized preactivated macromolecules via heterobifunctional cross
      linkers. Finally, functionalized two-dimensional S-layer lattices formed by
      rSbpA(31-1178)/STII/Cys exhibiting highly accessible cysteine residues in a well
      defined arrangement on the surface were utilized for the template-assisted
      patterning of gold nanoparticles.

PMID- 19402707
TI  - Site-specific polysialylation of an antitumor single-chain Fv fragment.
AB  - Protein pharmacokinetic modulation is becoming an important tool in the
      development of biotherapeutics. Proteins can be chemically or recombinantly
      modified to alter their half-lives and bioavailability to suit particular
      applications as well as improve side effect profiles. The most successful and
      clinically used approach to date is chemical conjugation with poly(ethylene
      glycol) polymers (PEGylation). Here, therapeutic protein half-life can be
      increased significantly while retaining biological function, reducing
      immunogenicity and cross-reaction. Naturally occurring alternatives to such
      synthetic polymers could have major advantages such as lower side effects due to
      biodegradability and metabolism. Polysialic acid (PSA) has been investigated as a
      pharmacokinetic modulatory biopolymer with many successful examples in
      preclinical and clinical development. Single-chain Fvs (scFvs) are a choice
      antibody format for human therapeutic antibody discovery. Because of their small
      size, they are rapidly eliminated from the circulation and often are rebuilt into
      larger proteins for drug development and a longer half-life. Here we show that
      chemical polysialylation can increase the half-life of an antiplacental alkaline
      (PLAP) and anticarcinoembryonic antigen (CEA) scFv (F1 and MFE-23, respectively)
      3.4-4.9-fold, resulting in a 10.6-15.2-fold increase in blood exposure. Amine
      directed coupling of the MFE-23 scFv reduced its immunoreactivity 20-fold which
      was resolved by site-specific polysialylation through an engineered C-terminal
      thiol residue. The site-specifically polysialylated MFE-23 scFv demonstrated up
      to 30-fold improved tumor uptake while displaying favorable tumor:normal tissue
      specificity. This suggests that engineering antibody fragments for site-specific
      polysialylation could be a useful approach to increase the half-life for a
      variety of therapeutic applications.

PMID- 19402708
TI  - Silencing an inhibitor unleashes a cytotoxic enzyme.
AB  - The ribonuclease inhibitor (RI) is a cytosolic protein and a potent inhibitor of
      bovine pancreatic ribonuclease (RNase A). Amphibian homologues and variants of
      RNase A that evade RI are cytotoxic. Here, we employ RNA interference along with
      amphibian and mammalian ribonucleases to demonstrate that RI protects cells
      against exogenous ribonucleases. These data indicate an imperative for the
      molecular evolution of RI and suggest a means of enhancing the cytotoxicity of
      mammalian ribonucleases.

PMID- 19402709
TI  - Impact of hepatic uptake transporters on pharmacokinetics and drug-drug
      interactions: use of assays and models for decision making in the pharmaceutical
      industry.
AB  - The ability to predict hepatic metabolic clearance is a key component in the
      design and selection of small molecule drug candidates within the pharmaceutical
      industry. The recognition that metabolism-transporter interplay can influence
      hepatic metabolic clearance has presented new challenges, both in terms of the
      creation of experimental systems suitable for an industry setting and also in
      developing an understanding of the pharmacokinetic concepts that underpin them.
      This paper reviews the pharmacokinetic principles that govern the kinetics of
      uptake transporter substrates. In addition, new data are presented from a range
      of test systems for assessing hepatic drug clearance and the impact of drug-drug
      interactions (DDIs).

PMID- 19402710
TI  - Structure of the cytoplasmic loop between putative helices II and III of the
      mannitol permease of Escherichia coli: a tryptophan and 5-fluorotryptophan
      spectroscopy study.
AB  - In this work, four single tryptophan (Trp) mutants of the dimeric mannitol
      transporter of Escherichia coli, EII(mtl), are characterized using Trp and 5
      fluoroTrp (5-FTrp) fluorescence spectroscopy. The four positions, 97, 114, 126,
      and 133, are located in a region shown by recent studies to be involved in the
      mannitol translocation process. To spectroscopically distinguish between the Trp
      positions in each subunit of dimeric EII(mtl), 5-FTrp was biosynthetically
      incorporated because of its much simpler photophysics compared to those of Trp.
      The steady-state and time-resolved fluorescence methodologies used point out that
      all four positions are in structured environments, both in the absence and in the
      presence of a saturating concentration of mannitol. The fluorescence decay of all
      5-FTrp-containing mutants was highly homogeneous, suggesting similar
      microenvironments for both probes per dimer. However, Stern-Volmer quenching
      experiments using potassium iodide indicate different solvent accessibilities for
      the two probes at positions 97 and 133. A 5 A two-dimensional (2D) projection map
      of the membrane-embedded IIC(mtl) dimer showing 2-fold symmetry is available. The
      results of this work are in better agreement with a 7 A projection map from a
      single 2D crystal on which no symmetry was imposed.

PMID- 19402711
TI  - anti-Oligoannelated THF moieties: synthesis via push-pull-substituted
      cyclopropanes.
AB  - The first synthesis of anti-fused oligoannelated THF moieties is reported. The
      key transformation of the synthetic sequence, consisting of cyclopropanation,
      reduction and oxidation, is the expansion of a push-pull-substituted three
      membered ring into a five-membered enol ether system. A repetition of the
      sequence allows the creation of oligoacetals up to a nonacyclic system.

PMID- 19402712
TI  - Two site-directed mutations are required for the conversion of a sugar
      dehydratase into an aminotransferase.
AB  - L-colitose and d-perosamine are unusual sugars found in the O-antigens of some
      Gram-negative bacteria such as Escherichia coli, Vibrio cholerae, and Salmonella
      enterica, among others. The biosynthetic pathways for these two sugars begin with
      the formation of GDP-mannose from d-mannose 1-phosphate and GTP followed by the
      subsequent dehydration and oxidation of GDP-mannose to yield GDP-4-keto-6
      deoxymannose. Following the production of GDP-4-keto-6-deoxymannose, the two
      pathways diverge. In the case of GDP-perosamine biosynthesis, the next step
      involves an amination reaction at the C-4' position of the sugar, whereas in GDP
      colitose production, the 3'-hydroxyl group is removed. The enzymes catalyzing
      these reactions are GDP-perosamine synthase and GDP-4-keto-6-deoxymannose-3
      dehydratase (ColD), respectively. Both of these enzymes are pyridoxal 5'
      phosphate (PLP) dependent, and their three-dimensional structures place them into
      the well-characterized aspartate aminotransferase superfamily. A comparison of
      the active site architecture of ColD from E. coli (strain 5a, type O55:H7) to
      that of GDP-perosamine synthase from Caulobacter crescentus CB15 suggested that
      only two mutations would be required to convert ColD into an aminotransferase.
      Here we present a combined structural and functional analysis of the ColD
      S187N/H188K mutant protein that, indeed, has been converted from a sugar
      dehydratase into an aminotransferase.

PMID- 19402715
TI  - Multisite structure of PbWO(4):Eu(3+) crystals investigated by site-selective
      laser-excitation spectroscopy.
AB  - Defect structures of Eu(3+)-doped PbWO(4) crystals are investigated by site
      selective laser-excitation spectroscopy. The excitation spectrum of the (7)F(0) -
      > (5)D(0) transition shows a strong dependence on Eu(3+)-concentration in PbWO(4)
      crystals. Only one substitution site for Eu(3+) is identified in the
      PbWO(4):Eu(3+) (0.01 at.%) crystal, while at least six inequivalent sites are
      observed in the PbWO(4):Eu(3+) (0.05 and 0.5 at.%) crystals. The charge
      compensation mechanisms for the observed sites are discussed in relation with
      annealing effects and temperature-dependent decay curves. The dominant site for
      Eu(3+) in the PbWO(4) lattice seems to be due to a formation of Eu(Pb)(3+)
      V(Pb)'' dipole by charge compensation. The minor sites for Eu(3+) are
      attributable to the Eu(Pb)(3+)-O(i)'' dipole, a site perturbed by Eu(Pb)(3+*)
      V(Pb)'' dipole, and a clustering of Eu(3+) in the PbWO(4) lattice. The energy
      transfer and site distribution of Eu(3+) are discussed in PbWO(4):Eu(3+) (0.01,
      0.05, and 0.5 at.%).

PMID- 19402714
TI  - Spatial pH jump measures chemical kinetics in a steady-state system.
AB  - We measure chemical kinetics in a steady-state solution where we create a
      microscopic open region with conditions different from the bulk. Individual
      reactant molecules spontaneously diffuse through this "reaction volume". We
      measure the changes which take place within their short residence time in the
      volume. The advantage of this approach is that the time resolution is limited
      only by the residence time tau(D) of the molecules in the reaction volume (which
      can easily be <50 mus), while the time taken to average the data can be
      arbitrarily long. In addition, if the chemical changes are reversible, the system
      is always in a steady state, and no replenishment of the reactants is necessary.
      Also, the total specimen volume required can be very small (<20 muL). We
      demonstrate the scheme by measuring the protonation induced changes of the
      fluorescence properties of fluorescein. We first show that a pH jump of >1 unit
      can be achieved by multiphoton excitation of ortho-nitro benzaldehyde (o-NBA). We
      then perform fluorescence correlation spectroscopy (FCS) to show that the
      residence time tau(D) of fluorescein in this low-pH region is approximately 30
      mus. Subsequently, we use time correlated single photon counting (a widely used
      probing technique with an inherently long averaging time), and show that the data
      can be averaged for an arbitrarily long time, yet it captures the fluorescence
      lifetime of the low-pH species which exists only for the short time tau(D).
      Finally, we show that the time resolution can be tuned by over 3 orders of
      magnitude, by changing the focal volume and by changing the viscosity of the
      solution. The latter experiment also shows that small chemically induced changes
      in the fluorescence lifetime can be resolved by our technique.

PMID- 19402713
TI  - Using substrate specificity of antiplasmin-cleaving enzyme for fibroblast
      activation protein inhibitor design.
AB  - Circulating antiplasmin-cleaving enzyme (APCE), a prolyl-specific serine
      proteinase, is essentially identical to membrane-inserted fibroblast activation
      protein (FAP) that is transiently expressed during epithelial-derived cancer
      growth. Human precursive alpha(2)-antiplasmin (Met-alpha(2)AP), the only known
      physiologic substrate for APCE, is cleaved N-terminally to Asn-alpha(2)AP that is
      rapidly cross-linked to fibrin and protects it from digestion by plasmin.
      Identifying a specific inhibitor of APCE/FAP continues to be intensely pursued.
      Recombinant FAP cleavage of peptide libraries of short amino acid sequences
      surrounding the scissile bond, -Pro(12)-Asn(13)-, indicated that P2 Gly and P1
      Pro are required, just as we found for APCE. We examined cleavage of P4-P4'
      peptides, using 19 amino acid substitutions at each position and selected ones in
      P8-P5. K(m) values determined for peptide substrates showed that P7 Arg has the
      highest affinity for APCE. Peptide cleavage rate increased with Arg in P6 rather
      than P5 or native P7. Placing Arg in P4 or P8 reduced cleavage rates
      dramatically. Cleavage of substrates with extended peptide sequences before or
      after the scissile bond showed endopeptidase to be superior to dipeptidase
      activity for APCE. A substrate analogue inhibitor, Phe-Arg-(8-amino-3,6
      dioxaoctanoic acid)-Gly-[r]-fluoropyrrolidide, inhibited APCE with a K(i) of 54
      microM but not dipeptidyl peptidase IV even at 2 mM. The inhibitor also blocked
      cleavage of Met-alpha(2)AP with an IC(50) of 91 microM. Replacing Arg with Gly at
      the same distance from fluoropyrrolidide as P7 Arg is from P1 Pro reduced its
      inhibition of APCE approximately 10-fold. Results indicate that Arg at P5, P6, or
      P7 distances from P1 enhances affinity and efficiency of substrates or inhibitors
      toward APCE or FAP.

PMID- 19402716
TI  - Comparative theoretical and experimental study of the radiation-induced
      decomposition of glycine.
AB  - The radiation-induced decomposition of glycine is studied using a combination of
      near-edge X-ray absorption fine structure (NEXAFS) measurements and DFT
      calculations. The measured spectra show strong dose- or time-dependent effects
      consistent with a complex, multistep decomposition. Principal component analysis
      was used to determine the number of distinct molecules that were needed to
      explain the observed changes in the measured spectra, and the emerging absorption
      features are assigned to various product molecules through comparison with
      simulated spectra of several model compounds. It is clear from the experiment
      that the major effect of soft X-ray irradiation is the fragmentation of the
      molecule, primarily at the carbonyl sites. Peptide formation is shown to occur
      under irradiation; a condensation reaction initiated by the removal of a carbonyl
      oxygen is the proposed mechanism. This study utilizes a novel approach to the
      study of radiation damage that can occur during measurements and suggests that it
      may be possible to use simulated model spectra to correct for these effects in
      measured spectra.

PMID- 19402717
TI  - Ab initio study of structural, electronic, and magnetic properties of
      V(n)(C(60))(m) complexes.
AB  - We have studied structural, electronic, and magnetic properties of transition
      metal-fullerene complexes V(n)(C(60))(m), (n, m) = (1, 1), (1, 2), (2, 3), (3,
      4), (4, 4), by means of a density functional theory method. We have examined
      relative stabilities of complexes with different V-C(60) binding sites (V atoms
      are bound to either pentagonal or hexagonal rings of C(60)) and with different
      stacking configurations (linear or nonlinear). The linearly stacked sandwichlike
      complexes with V atoms binding to hexagonal rings of C(60) are the most stable
      for (n, m) = (n, n + 1), although nonlinearly stacked configurations can be
      energetically competitive. For (n, m) = (1, 1), the V atom tends to bind to a
      pentagonal ring of the C(60) molecule. For (n, m) = (4, 4), a riceball-like
      structure is found to be the most stable. Except for (n, m) = (1, 1), the lowest
      energy structures of the complexes are generally in their lowest spin states.

PMID- 19402719
TI  - Raman microscopes.
AB  - Analysis of scattered light can achieve high spatial resolution without labeling
      or sample preparation.

PMID- 19402720
TI  - Grazing exit micro X-ray fluorescence analysis of a hazardous metal attached to a
      plant leaf surface using an X-ray absorber method.
AB  - If human beings or animals repeatedly ingest plant leaves contaminated with
      minute quantities of hazardous metals (Pb, As, Hg, Cd, etc.), the metals will
      gradually accumulate in their bodies. When the quantities of the metals in the
      bodies reach toxic levels, they may cause serious symptoms of poisoning.
      Therefore, it is significant to detect and analyze the minute quantities of
      hazardous metals that attach to plant leaves in terms of epidemiology and disease
      prevention. We developed grazing exit micro X-ray fluorescence analysis (GE-micro
      XRF), which was expected to analyze the localized surface of an aqueous plant
      leaf with a much faster and simpler sample treatment than with conventional
      analytical methods, to detect Pb attached to a surface of a leaf of Camellia
      hiemalis. A micro X-ray beam was produced by using a polycapillary X-ray lens. GE
      v-XRF is a grazing exit X-ray analysis (GE-XA) method in which X-rays emitted
      from only the near-surface region of a specimen are selectively detected under a
      grazing exit angle condition (extremely low exit angle near 0 degrees). In any GE
      XA method, X-rays emitted from inside the specimen must be absorbed inside the
      specimen and attenuated when X-rays pass through the specimen. However, we
      deduced that X-rays emitted from inside aqueous organic material such as a plant
      leaf are scarcely absorbed because X-ray absorption in any aqueous organic
      material is much smaller than that in most metallic and semiconductor materials,
      which was analyzed with GE-XA methods. Therefore, we have developed a novel GE
      micro-XRF method in which a chip of a silicon wafer is placed between the
      analyzed leaf and an X-ray detector as an absorber of the X-rays emitted from
      inside the leaf. As a result of GE-XRF analysis of a leaf dipped in Pb standard
      solution using the X-ray absorber, we have for the first time selectively
      detected X-rays emitted from the near-surface region of an aqueous plant leaf.
      Therefore, we have detected X-rays emitted from Pb with much higher
      peak/background ratios (P/B ratios) as compared to those of conventional XRF
      analysis. In the analysis, we also found a difference in element distributions
      between the leaf surface and its interior. Therefore, we observed and analyzed a
      cross section of the leaf with a SEM-EDX to confirm the validity of this result.
      The result of the analysis of the cross section has been in excellent agreement
      with that of the XRF analysis.

PMID- 19402721
TI  - Subtyping of the influenza virus by high resolution mass spectrometry.
AB  - High resolution, high mass accuracy mass spectra of hemagglutinin and whole virus
      digests of influenza are shown to be able to be used to type and subtype the
      major circulating forms of the virus in humans. Conserved residues and peptide
      segments of the hemagglutinin antigen have been identified across type A and B
      strains, and for type B strains of the Yamagata 16/88 and Victoria 2/87 lineages.
      The theoretical masses for the protonated peptide ions for tryptic peptides of
      conserved sequence were subsequently shown to be unique in mass when compared to
      in silico generated peptides from all influenza viral protein sequences and those
      proteins known to contaminate virus preparations. The approach represents a more
      rapid and direct approach with which to type and subtype the virus that is of
      critical need to prepare strategies and treatments in the event of a local
      epidemic or global pandemic.

PMID- 19402722
TI  - "One-pot" process for fabrication of organic-silica hybrid monolithic capillary
      columns using organic monomer and alkoxysilane.
AB  - A "one-pot" process for the preparation of organic-silica hybrid capillary
      monolithic columns by concurrently using organic monomers and alkoxysilanes was
      described. In this process, the hydrolyzed alkoxysilanes of tetramethoxysilane
      (TMOS) and vinyltrimethoxysilane (VTMS) as precursors for the synthesis of a
      silica-based monolith using the sol-gel method and the organic monomer
      (allyldimethyldodecylammonium bromide (ADDAB) or acrylamide (AA)) with vinyl
      groups for free radical polymerization along with the initiator of
      azobisisobutyronitrile (AIBN) were concurrently introduced into a pretreated
      capillary; after that, the polycondensation of alkoxysilanes and the
      copolymerization of organic monomers and as-precondensed siloxanes were
      subsequently carried out within the confines of a capillary at the proper
      reaction conditions. Two types of organic-silica hybrid capillary monolithic
      columns with hydrophobic and hydrophilic properties have been fabricated,
      respectively, by this "one-pot" process using two different organic monomers of
      ADDAB and AA. The morphologies of the synthesized organic-silica hybrid
      monolithic columns were characterized by scanning electron microscopy (SEM). The
      performances of these organic-silica monolithic columns were investigated by
      capillary electrochromatography (CEC). The retention behaviors of the neutral and
      polar compounds on the resulting hydrophobic and hydrophilic organic-silica
      hybrid monolithic columns confirmed the successful incorporation of organic
      monomers in the silica monolithic matrix. In addition, the ADDA-silica hybrid
      capillary monolithic column was also applied in the analysis of tryptic digests
      of bovine serum albumin (BSA) and mouse liver extract by microliquid
      chromatography-tandem mass spectrometry (microLC-MS/MS) for demonstrating its
      potential in proteome analysis.

PMID- 19402723
TI  - Polymeric membrane electrodes with high nitrite selectivity based on rhodium(III)
      porphyrins and salophens as ionophores.
AB  - Several porphyrin and salophen complexes with Rh(III) are examined as ionophores
      to prepare nitrite selective polymeric membrane electrodes. All ionophores tested
      exhibit preferred selectivity toward nitrite anion. Enhanced potentiometric
      nitrite selectivity is observed in the presence of either lipophilic anionic as
      well as cationic sites within the membranes, suggesting that the ionophores can
      function via either a charged or a neutral carrier response mechanism. Among a
      range of complexes and membrane formulations examined, optimal nitrite
      selectivity and reversible response down to 5 x 10(-6) M is achieved using
      Rh(III)-tetra(t-butylphenylporphyrin) as the ionophore in the presence of
      lipophilic cationic sites in plasticized poly(vinyl chloride) membrane. Response
      times are substantially longer than typical membrane electrodes apparently
      because of a slow nitrite ligation reaction with Rh(III); however, a significant
      improvement in dynamic EMF response can be realized by optimizing the membrane
      formulation and increasing the temperature. The selectivity observed with these
      membranes is greater than the best nitrite selective electrodes reported to date
      in the literature based on lipophilic Co(III)-corrin complexes, allowing the new
      nitrite electrodes to be utilized to determine the level of nitrite in meats with
      good correlation to the colorimetric Griess assay method.

PMID- 19402725
TI  - Infrared spectroscopy of bis[(perfluoroalkyl)sulfonyl] imide ionomer membrane
      materials.
AB  - Structural properties of the proton-exchanged forms of
      bis[(perfluoroalkyl)sulfonyl] imide (PFSI) ionomer materials were investigated.
      The hydration and dehydration of samples prepared as thin films and freestanding
      membrane were probed by applying transmission infrared spectroscopy. Spectral
      bands were assigned and effects of water incorporation into membrane pores and
      channels were understood by drawing upon results from related measurements
      performed on the structurally similar, perfluorosulfonic acid ionomer, Nafion.
      Both PFSI and Nafion membrane materials display a prominent infrared absorbance
      band near 1060 cm(-1) that arises from a vibrational mode of the ionizable group
      present on the side chains that extend from the poly(tetrafluoroethylene)
      backbone on the polymers. The mode can be traced to symmetric stretching of the 
      SO(3)(-) (sulfonate) group in Nafion and to antisymmetric S-N-S stretching within
      the sulfonyl imide end group (-SO(2)(N(-))SO(2)CF(3)) in the PFSI materials. For
      Nafion samples, the position and width of the band near 1060 cm(-1) are strongly
      sensitive to membrane hydration, whereas the band position and shape change only
      slightly during hydration and dehydration of PFSI materials. The possibility for
      greater charge delocalization over the sulfonyl imide moiety and shielding of
      hydrophilic species by the terminal -CF(3) group are suggested to explain the
      differences. These effects also likely influence the stretching modes of the side
      chain C-O-C groups. A pair of bands, sensitive to hydration and traceable to
      different C-O-C groups in a side chain, is present in the 970-990 cm(-1) region
      of Nafion. However, the two features are not well resolved and are less sensitive
      to hydration in spectra of PFSI samples. The most intense ionomer spectral bands
      arise from modes involving C-F stretching motion and appear between 1150 and 1250
      cm(-1). Toward the high energy side of the envelope, there is substantial overlap
      with features of sulfonate group antisymmetric SO stretching modes in Nafion, but
      SO stretching modes of the sulfonyl imide moiety are higher in energy and better
      resolved in spectra of the PFSIs. During water uptake from a dry state into PFSI
      materials, a progression of features characteristic of solvated H(3)O(+) species
      appears across the water O-H stretching (2800-3800 cm(-1)) and H-O-H bending
      (1500-2000 cm(-1)) regions, similar to responses observed for water inside proton
      exchanged Nafion.

PMID- 19402724
TI  - Transverse electronic transport in double-stranded DNA nucleotides.
AB  - We calculate the transverse current through double-stranded DNA nucleotides using
      ab initio techniques in order to establish a protocol to recognize the type and
      sequence of double-stranded DNA nucleotides. The distinct current-voltage
      features between nucleotides are used as signatures for their characterization
      and sequencing. Extended bulk gold electrodes as well as extensions of the DNA
      backbones are tested as contacts for the electron transport, yielding currents 2
      orders of magnitude larger for the former. The addition of Na or H positive
      counterions improves the signal levels, thus leading to a better discrimination,
      especially when sodium cations are added.

PMID- 19402726
TI  - Catanionic vesicles formed with arginine-based surfactants and 1,2-dipalmitoyl-sn
      glycero-3-phosphate monosodium salt.
AB  - We report on mixing an anionic diacyl phospholipid (1,2-dipalmitoyl-sn-glycero-3
      phosphate monosodium salt, DPPA) with either monoacyl and diacyl arginine-based
      surfactants. These mixtures are part of the rich family of pseudo-triple-chain
      and pseudo-tetra-chain catanionic mixtures, respectively. Vesicle size and zeta
      potential were measured at several mixing ratios. Additional information on
      counterion binding, vesicle size, and integrity was obtained from ion selective
      electrode and Cryo-TEM measurements. Addition of positively charged surfactants
      to DPPA results in an increase of vesicle size. However, zeta-potential shows
      different trends, depending on whether water or acid media are used as solvent.
      In the latter, zeta-potential values progressively approach 0 upon addition of
      amino acid based surfactants. In water, surprisingly, zeta-potential values
      become more negative. The results are discussed in terms of modifications in
      counterion binding and vesicle size.

PMID- 19402727
TI  - Phase equilibria study of the binary systems (1-butyl-3-methylimidazolium
      thiocyanate ionic liquid + organic solvent or water).
AB  - (Solid + liquid) phase equilibria (SLE) for the binary systems, ionic liquid (IL)
      1-butyl-3-methylimidazolium thiocyanate [BMIM][SCN] with an alcohol (1-octanol, 1
      nonanol, 1-decanol, 1-undecanol, or 1-dodecanol) or water, and (liquid + liquid)
      phase equilibria (LLE) for the binary systems of [BMIM][SCN] with an alkane (n
      hexane, n-heptane, n-octane, n-nonane, or n-decane), benzene, an alkylbenzenes
      (toluene or ethylbenzene), tetrahydrofuran (THF), cycloalkanes (cyclohexane or
      cycloheptane), or ethers (di-n-propyl ether, di-n-butyl ether, di-n-pentyl ether,
      n-butylmethyl ether, tert-butylmethyl ether (MTBE), or tert-butylethyl ether
      (ETBE)) have been determined at ambient pressure. A dynamic method was used over
      a broad range of mole fractions and temperatures from 250 to 430 K. In the case
      of systems IL + alkane, cycloalkane, or ether, the mutual immiscibility with an
      upper critical solution temperature (UCST) was detected, and in the systems of IL
      + benzene, alkylbenzene, or THF, the mutual immiscibility with a lower critical
      solution temperature (LCST) was observed. UV-vis spectroscopy was used to
      determine the very small compositions of the IL in the n-hexane (about 2 x 10(-5)
      IL mole fraction), benzene (about 2 x 10(-3) IL mole fraction), cyclohexane
      (about 2 x 10(-5) IL mole fraction), and THF (about 1.2 x 10(-2) IL mole
      fraction). For the binary systems containing alcohol, it was noticed that with
      increasing chain length of an alcohol, the solubility decreases. The basic
      thermal properties of the pure IL, that is, the glass-transition temperature as
      well as the heat capacity at the glass-transition temperature, have been measured
      using a differential scanning microcalorimetry technique (DSC). Decomposition of
      the IL was detected by the simultaneous TG/DTA experiments. Well-known UNIQUAC,
      Wilson, and NRTL equations have been used to correlate the experimental SLE data
      sets for alcohols and water. For the systems containing immiscibility gaps {IL +
      alkane, benzene, alkylbenzene, cycloalkane, tetrahydrofuran, or ether}, the
      parameters of the LLE correlation have been derived using the NRTL equation.

PMID- 19402728
TI  - Simulating the kinetics and thermodynamics of transitions via forward
      flux/umbrella sampling.
AB  - First, a technique is introduced for computing equilibrium probability
      distributions for transitional rare-event simulations by combining the ensemble
      of trajectories generated by forward flux sampling (FFS) and by umbrella sampling
      (US) in multiple windows along an order parameter of interest; this method is
      denoted FFS-US. Second, the FFS algorithm is extended to obtain rate constants of
      partial transitions involving intermediate states from a single simulation; this
      is denoted "multiple state" FFS. For the FFS-US method, a FFS algorithm
      (preoptimized for order parameter and staging) is used to take advantage of its
      zero potential bias of phase-space sampling to gather histogram data with which
      to jump start the US and get the equilibrium distributions. In this way, kinetic
      data (like the rate constants and the transition path ensemble) and the
      underlying free-energy landscape (or probability distribution) of the system are
      obtained efficiently and concurrently. The applicability of these techniques is
      illustrated by studying several test systems, including two that involve
      potential energy surfaces having multiple metastable states and transition
      pathways, representative of complex kinetic behavior.

PMID- 19402729
TI  - Solvation of dimethyl succinate in a sodium hydroxide aqueous solution. A
      computational study.
AB  - Molecular dynamics simulations were carried out to study dimethyl
      succinate/water/NaOH solutions. The potential of mean force method was used to
      determine the transport mechanism of a dimethyl succinate (a diester) molecule
      across the aqueous/vapor interface. The computed number density profiles show a
      strong propensity for the diester molecules to congregate at the interface, with
      the solubility of the diester increasing with increasing NaOH concentration. It
      is observed that the major contribution to the interfacial solvation free-energy
      minimum is from electrostatic interactions. Even at higher NaOH concentrations,
      the increasing electrostatic interaction between the diester and ions is not
      large enough to favor the solvation of diester in bulk solutions. The calculated
      solvation free energies are found to be -2.6 to -3.5 kcal/mol in variant
      concentrations of NaOH aqueous solutions. These values are in qualitative
      agreement with the corresponding experimental measurements. The computed surface
      potential indicates that the contribution of diester molecules to the total
      surface potential is about 25%, with the major contribution from interfacial
      water molecules.

PMID- 19402730
TI  - Pigment organization and energy level structure in light-harvesting complex 4:
      insights from two-dimensional electronic spectroscopy.
AB  - Photosynthetic light-harvesting antennae direct energy collected from sunlight to
      reaction centers with remarkable efficiency and rapidity. Despite their common
      function, the pigment-protein complexes that make up antenna systems in different
      types of photosynthetic organisms exhibit a wide variety of structural forms.
      Some individual organisms express different types of complexes depending on
      growth conditions. For example, purple photosynthetic bacteria Rp. palustris
      preferentially synthesize light-harvesting complex 4 (LH4), a structural variant
      of the more common and widely studied LH2, when grown under low-light conditions.
      Here, we investigate the ultrafast dynamics and energy level structure of LH4
      using two-dimensional (2D) electronic spectroscopy in combination with
      theoretical simulations. The experimental data reveal dynamics on two distinct
      time scales, consistent with coherent dephasing within approximately the first
      100 fs, followed by relaxation of population into lower-energy states on a
      picosecond time scale. We observe excited state absorption (ESA) features marking
      the existence of high-energy dark states, which suggest that the strongest dipole
      dipole coupling in the complex occurs between bacteriochlorophyll transition
      dipole moments in an in-line geometry. The results help to refine the current
      understanding of the pigment organization in the LH4 complex, for which a high
      resolution crystal structure is not yet available.

PMID- 19402731
TI  - Model of human butyrylcholinesterase tetramer by homology modeling and dynamics
      simulation.
AB  - A mutant of human butyrylcholinesterase (BChE) with high activity against cocaine
      would be highly promising as a drug for therapeutic treatment of cocaine abuse
      and overdose. It is desirable to design a recombinant BChE mutant with a long
      half-life in human circulation. Studies showed that BChE subunits can be
      assembled by a peptide containing the proline-rich attachment domain (PRAD) to
      form a stable tetramer. The models of BChE tetramer complexed with PRAD with
      various sequences have been constructed, in the present study, on the basis of
      homology modeling and molecular dynamics simulation of explicit water-solvated
      systems. The 3D models enable us to understand how the BChE subunits are arranged
      in the tetramer and how the tetramerization domain of BChE is associated with
      PRAD to form a stable tetramer of human BChE. It has been shown that the six
      conserved hydrophobic residues located on the C-terminal of BChE are responsible
      for the key electrostatic and hydrophobic interactions between the
      tetramerization domain of BChE and PRAD. The simulated tetramer structures
      suggest that mutation of three residues, i.e., Phe547, Met554, and Phe561, to
      other hydrophobic residues may be beneficial for increasing the binding between
      the tetramerization domain of BChE and PRAD. Thus, the detailed structural
      insights obtained from this study may be valuable for rational design of a
      recombinant BChE tetramer with a longer residence time in circulation.

PMID- 19402732
TI  - Hydrogen abstraction from deoxyribose by a neighboring 3'-uracil peroxyl radical.
AB  - Theoretical examination of the reactivity of the uracil-5-peroxyl radical when
      abstracting a hydrogen atom from a neighboring 5'-deoxyribose in 5'-ApU-5-peroxyl
      3' has been performed using density functional theory with the MPWB1K functional.
      Halogenated uracils are often used as radiosensitizers in DNA since the reactive
      uracil-5-yl radical is formed upon radiation and is known to create strand break
      and alkali-labile sites. Under aerobic conditions, such as in the cell, it has
      been proposed that the uracil-5-peroxyl radical is formed and would be the
      damaging agent. Our results show low reactivity for the uracil-5-peroxyl radical,
      determined by calculating the activation and reaction energies for the plausible
      hydrogen abstraction sites C1', C2', and C3' of the neighboring 5'-deoxyribose.
      These findings support the hypothesis that hydrogen abstraction primarily occurs
      by the uracil-5-yl radical, also under aerobic conditions, prior to formation of
      the peroxyl radical.

PMID- 19402733
TI  - Comment on "characterization of the ability of CO(2) to act as an antisolvent for
      ionic liquid/organic mixtures".

PMID- 19402737
TI  - An iterative strategy for precursor ion selection for LC-MS/MS based shotgun
      proteomics.
AB  - Currently, the precursor ion selection strategies in LC-MS mainly choose the most
      prominent peptide signals for MS/MS analysis. Consequently, high-abundance
      proteins are identified by MS/MS of many peptides, whereas proteins of lower
      abundance might elude identification. We present a novel, iterative and result
      driven approach for precursor ion selection that significantly increases the
      efficiency of an MS/MS analysis by decreasing data redundancy and analysis time.
      By simulating different strategies for precursor ion selection on an existing
      data set, we compare our method to existing result-driven strategies and evaluate
      its performance with regard to mass accuracy, database size, and sample
      complexity.

PMID- 19402736
TI  - Selective enrichment of azide-containing peptides from complex mixtures.
AB  - A general method is described to sequester peptides containing azides from
      complex peptide mixtures, aimed at facilitating mass spectrometric analysis to
      study different aspects of proteome dynamics. The enrichment method is based on
      covalent capture of azide-containing peptides by the azide-reactive cyclooctyne
      (ARCO) resin and is demonstrated for two different applications. Enrichment of
      peptides derived from cytochrome c treated with the azide-containing cross-linker
      bis(succinimidyl)-3-azidomethyl glutarate (BAMG) shows several cross-link
      containing peptides. Sequestration of peptides derived from an Escherichia coli
      proteome, pulse labeled with the bio-orthogonal amino acid azidohomoalanine as
      substitute for methionine, allows identification of numerous newly synthesized
      proteins. Furthermore, the method is found to be very specific, as after
      enrichment over 87% of all peptides contain (modified) azidohomoalanine.

PMID- 19402738
TI  - Active protein-functionalized poly(poly(ethylene glycol) monomethacrylate)
      Si(100) hybrids from surface-initiated atom transfer radical polymerization for
      potential biological applications.
AB  - Protein-resistant poly(poly(ethylene glycol)monomethacrylate)-graft-Si(100), or
      Si-g-P(PEGMA) hybrids, were prepared via surface-initiated atom transfer radical
      polymerization (ATRP) of the poly(ethylene glycol)monomethacrylate (PEGMA)
      macromonomer from the hydrogen-terminated Si(100) surface (Si-H surface). The
      resultant robust Si-C bonded P(PEGMA) brushes can be further functionalized by
      the immobilization of human immunoglobulin (IgG) protein via different
      strategies, namely, the direct use of the alkyl halide chain ends preserved
      throughout the ATRP process and the postmodification of the hydroxyl side chains
      with by 1,1'-carbonyldiimidazole (CDI) or succinic anhydride (SA). The CDI
      exhibited a higher efficiency in activating the hydroxyl groups for coupling
      proteins. The surface density of the immobilized protein above 2.5 microg/cm(2)
      could be readily achieved. The distribution of active protein-docking sites on
      the Si-C bonded P(PEGMA) brushes can be also controlled by controlling the brush
      length. The resulting IgG-coupled Si-g-P(PEGMA) hybrid surface interacts only and
      specifically with the anti-IgG protein, while the dense P(PEGMA) brushes
      effectively prevent nonspecific protein binding and fouling. The simple
      concomitant incorporation of protein-resistant P(PEGMA) brushes and highly
      specific and active protein onto silicon surfaces via robust Si-C bonding should
      readily endow the silicon substrates with new and interesting properties for
      applications in silicon-based protein sensors or microarrays.

PMID- 19402739
TI  - Genetic testing and sports medicine ethics.
AB  - Sports medicine ethics is neither a well established branch of sports medicine
      nor of medical ethics. It is therefore important to raise to more general
      awareness some of the significant ethical implications of sports medicine
      practices. The field of genetics in sports is likewise in its infancy and raises
      significant ethical concerns. It is not yet clear how genetics will alter our
      understanding of human potential and performance in sports. While a number of
      professional medical bodies accept genetic interventions of a therapeutic nature,
      we argue that the use of genetic technologies to predict sports potential may
      well breach both the European bioethics convention and North American anti
      discrimination legislation, which are designed to support important ethical
      ideals and the ongoing commitment of the physician to the welfare of their
      patient. We highlight further ethical problems associated with confidentiality
      and consent that may arise in genetic testing as opposed to more conventional
      methods of testing in sports medicine. We conclude that genetic testing in sport
      that is not strictly limited to the protection of the athlete against harm,
      should be viewed in a very sceptical light by sports medicine professionals.

PMID- 19402741
TI  - Characteristics of physical activity guidelines and their effect on adherence: a
      review of randomized trials.
AB  - Prescription characteristics and guidelines of recommended physical activity have
      been suggested as factors that may affect behavioural adherence; however, no
      review has critically appraised the current evidence. Thus, the purpose of this
      article was to review the effect of frequency, intensity, duration and mode on
      physical activity adherence and provide meta-analytical summaries of the
      findings. A total of 27 peer-reviewed studies met inclusion criteria and random
      effects meta-analytical procedures, correcting for sampling bias, were employed
      where possible. Overall, results showed that the effect of physical activity
      guideline characteristics on behavioural adherence is not particularly robust as
      evidenced by a lack of unified findings and almost no evidence for the
      interaction among these factors (e.g. volume of activity and energy expenditure).
      Frequency (d = 0.08), intensity (d = 0.02), duration (d = 0.05) and mode of
      activity (ds = 0.03-0.10) showed generally null/trivial effects. Factors
      unrelated to the recommended guidelines may be of greater importance when
      considering behavioural adherence issues. Social cognitive, personality, and
      environmental or socioeconomic factors have amassed considerable evidence as
      correlates or determinants of physical activity, and health promoters may wish to
      consider these variables before basic physical activity characteristics.

PMID- 19402740
TI  - Platelet-rich therapies in the treatment of orthopaedic sport injuries.
AB  - Biomedical sciences have made major advances in understanding how tissues repair,
      and the signalling mechanisms required to achieve this goal are progressively
      being dissected. Advances in the understanding of tissue repair mechanisms and
      the pivotal role of growth factors have stimulated the use of platelet-rich
      therapies by orthopaedic surgeons and sports physicians, mainly with the aim of
      stimulating and enhancing tissue healing. Autologous activated platelets retained
      in fibrin matrices are used as a source of molecular signals that control cell
      fate, including cell growth, cell differentiation and the synthesis of diverse
      functional proteins. Thus far, platelet-rich technologies have spawned additional
      ambitious endeavours, including surgical and non-surgical treatments in sports
      orthopaedics. Reconstruction of anterior cruciate ligament and tendon surgery and
      treatment of joint injuries, tendinopathy or muscle tears are but a few examples
      of the potential applications of this technology in the field of orthopaedic
      sports medicine. In the present article, some of the most important therapeutic
      applications using these approaches - especially preparation rich in growth
      factor (PRGF) technology - are presented, as are some of the limitations, anti
      doping concerns and future challenges in the field. In view of a general state of
      confusion, the concept of platelet-rich plasma needs rigorous definition
      associated with well characterized products and re-administration procedures.
      There is evidence that reconstruction of anterior cruciate ligament and tendon
      surgery combined with PRGF enhances healing and functional recovery; clinical
      evidence is also appearing in the literature regarding treatment of
      tendinopathies and osteoarthritis. Currently, the challenge lies in conducting
      randomized, controlled clinical trials to determine the essential qualities of
      these technologies. If anti-doping agencies clarify their regulatory guidelines,
      robust studies in athletes are expected to emerge. Although much research work
      lies ahead, the current knowledge points to a future in which platelet-rich
      therapies will continue improving existing conventional approaches to treatment
      of sports injuries.

PMID- 19402742
TI  - Swimming exercise: impact of aquatic exercise on cardiovascular health.
AB  - Swimming is an exercise modality that is highly suitable for health promotion and
      disease prevention, and is one of the most popular, most practiced and most
      recommended forms of physical activity. Yet little information is available
      concerning the influence of regular swimming on coronary heart disease (CHD).
      Exercise recommendations involving swimming have been generated primarily from
      unjustified extrapolation of the data from other modes of exercise (e.g. walking
      and cycling). Available evidence indicates that, similarly to other physically
      active adults, the CHD risk profile is more favourable in swimmers than in
      sedentary counterparts and that swim training results in the lowering of some CHD
      risk factors. However, the beneficial impact of regular swimming may be smaller
      than land-based exercises. In some cases, regular swimming does not appear to
      confer beneficial effects on some CHD risk factors. Moreover, swimming has not
      been associated with the reduced risks of developing CHD. Thus, extrapolation of
      research findings using land-based exercises into swimming cannot be justified,
      based on the available research. Clearly, more research is required to properly
      assess the effects of regular swimming on CHD risks in humans.

PMID- 19402745
TI  - Accelerated adaptive evolution on a newly formed X chromosome.
AB  - Sex chromosomes originated from ordinary autosomes, and their evolution is
      characterized by continuous gene loss from the ancestral Y chromosome. Here, we
      document a new feature of sex chromosome evolution: bursts of adaptive fixations
      on a newly formed X chromosome. Taking advantage of the recently formed neo-X
      chromosome of Drosophila miranda, we compare patterns of DNA sequence variation
      at genes located on the neo-X to genes on the ancestral X chromosome. This
      contrast allows us to draw inferences of selection on a newly formed X chromosome
      relative to background levels of adaptation in the genome while controlling for
      demographic effects. Chromosome-wide synonymous diversity on the neo-X is reduced
      2-fold relative to the ancestral X, as expected under recent and recurrent
      directional selection. Several statistical tests employing various features of
      the data consistently identify 10%-15% of neo-X genes as targets of recent
      adaptive evolution but only 1%-3% of genes on the ancestral X. In addition, both
      the rate of adaptation and the fitness effects of adaptive substitutions are
      estimated to be roughly an order of magnitude higher for neo-X genes relative to
      genes on the ancestral X. Thus, newly formed X chromosomes are not passive
      players in the evolutionary process of sex chromosome differentiation, but
      respond adaptively to both their sex-biased transmission and to Y chromosome
      degeneration, possibly through demasculinization of their gene content and the
      evolution of dosage compensation.

PMID- 19402744
TI  - A role for the PERIOD:PERIOD homodimer in the Drosophila circadian clock.
AB  - Circadian clocks in eukaryotes rely on transcriptional feedback loops, in which
      clock genes repress their own transcription resulting in molecular oscillations
      with a period of approximately 24 h. In Drosophila, the clock proteins Period
      (PER) and Timeless (TIM) operate in such a feedback loop, whereby they first
      accumulate in the cytoplasm of clock cells as a heterodimer. Nuclear
      translocation of the complex or the individual PER and TIM proteins is followed
      by repression of per and tim transcription, whereby PER seems to act as the prime
      repressor. We found that in addition to PER:TIM complexes, functional PER:PER
      homodimers exist in flies. Specific disruption of PER homodimers results in
      drastically impaired behavioral and molecular rhythmicity, pointing the
      biological importance of this clock protein complex. Analysis of PER subcellular
      distribution and repressor competence in the PER dimer mutant revealed defects in
      PER nuclear translocation and a disruption of rhythmic period transcription. The
      striking similarity of these phenotypes with that of reduced CKII activity
      suggests that the formation or function of the PER dimer is closely linked to
      this kinase. Our results confirm a previous structural model for PER and provide
      strong evidence that PER homodimers are important for circadian clock function.

PMID- 19402743
TI  - Exercise and fatigue.
AB  - Physical exercise affects the equilibrium of the internal environment. During
      exercise the contracting muscles generate force or power and heat. So physical
      exercise is in fact a form of mechanical energy. This generated energy will
      deplete the energy stocks within the body. During exercise, metabolites and heat
      are generated, which affect the steady state of the internal environment.
      Depending on the form of exercise, sooner or later sensations of fatigue and
      exhaustion will occur. The physiological role of these sensations is protection
      of the exercising subject from the deleterious effects of exercise. Because of
      these sensations the subject will adapt his or her exercise strategy. The
      relationship between physical exercise and fatigue has been the scope of interest
      of many researchers for more than a century and is very complex. The exercise
      intensity, exercise endurance time and type of exercise are all variables that
      cause different effects within the body systems, which in turn create different
      types of sensation within the subject's mind during the exercise. Physical
      exercise affects the biochemical equilibrium within the exercising muscle cells.
      Among others, inorganic phosphate, protons, lactate and free Mg2+ accumulate
      within these cells. They directly affect the mechanical machinery of the muscle
      cell. Furthermore, they negatively affect the different muscle cell organelles
      that are involved in the transmission of neuronal signals. The muscle metabolites
      produced and the generated heat of muscle contraction are released into the
      internal environment, putting stress on its steady state. The tremendous increase
      in muscle metabolism compared with rest conditions induces an immense increase in
      muscle blood supply, causing an increase in the blood circulatory system and gas
      exchange. Nutrients have to be supplied to the exercising muscle, emptying the
      energy stocks elsewhere in body. Furthermore, the contracting muscle fibres
      release cytokines, which in their turn create many effects in other organs,
      including the brain. All these different mechanisms sooner or later create
      sensations of fatigue and exhaustion in the mind of the exercising subject. The
      final effect is a reduction or complete cessation of the exercise. Many diseases
      speed up the depletion of the energy stocks within the body. So diseases amplify
      the effect of energy stock depletion that accompanies exercise. In addition, many
      diseases produce a change of mind-set before exercise. These changes of mind-set
      can create sensations of fatigue and exercise-avoiding behaviour at the onset of
      an exercise. One might consider these sensations during disease as a feed-forward
      mechanism to protect the subject from an excessive depletion of their energy
      stocks, to enhance the survival of the individual during disease.

PMID- 19402746
TI  - Proteomic studies of a single CNS synapse type: the parallel fiber/purkinje cell
      synapse.
AB  - Precise neuronal networks underlie normal brain function and require distinct
      classes of synaptic connections. Although it has been shown that certain
      individual proteins can localize to different classes of synapses, the
      biochemical composition of specific synapse types is not known. Here, we have
      used a combination of genetically engineered mice, affinity purification, and
      mass spectrometry to profile proteins at parallel fiber/Purkinje cell synapses.
      We identify approximately 60 candidate postsynaptic proteins that can be
      classified into 11 functional categories. Proteins involved in phospholipid
      metabolism and signaling, such as the protein kinase MRCKgamma, are major
      unrecognized components of this synapse type. We demonstrate that MRCKgamma can
      modulate maturation of dendritic spines in cultured cortical neurons, and that it
      is localized specifically to parallel fiber/Purkinje cell synapses in vivo. Our
      data identify a novel synapse-specific signaling pathway, and provide an approach
      for detailed investigations of the biochemical complexity of central nervous
      system synapse types.

PMID- 19402748
TI  - Coordinated movement of cytoplasmic and transmembrane domains of RyR1 upon
      gating.
AB  - Ryanodine receptor type 1 (RyR1) produces spatially and temporally defined Ca2+
      signals in several cell types. How signals received in the cytoplasmic domain are
      transmitted to the ion gate and how the channel gates are unknown. We used EGTA
      or neuroactive PCB 95 to stabilize the full closed or open states of RyR1. Single
      channel measurements in the presence of FKBP12 indicate that PCB 95 inverts the
      thermodynamic stability of RyR1 and locks it in a long-lived open state whose
      unitary current is indistinguishable from the native open state. We analyzed two
      datasets of 15,625 and 18,527 frozen-hydrated RyR1-FKBP12 particles in the closed
      and open conformations, respectively, by cryo-electron microscopy. Their
      corresponding three-dimensional structures at 10.2 A resolution refine the
      structure surrounding the ion pathway previously identified in the closed
      conformation: two right-handed bundles emerging from the putative ion gate (the
      cytoplasmic "inner branches" and the transmembrane "inner helices"). Furthermore,
      six of the identifiable transmembrane segments of RyR1 have similar organization
      to those of the mammalian Kv1.2 potassium channel. Upon gating, the distal
      cytoplasmic domains move towards the transmembrane domain while the central
      cytoplasmic domains move away from it, and also away from the 4-fold axis. Along
      the ion pathway, precise relocation of the inner helices and inner branches
      results in an approximately 4 A diameter increase of the ion gate. Whereas the
      inner helices of the K+ channels and of the RyR1 channel cross-correlate best
      with their corresponding open/closed states, the cytoplasmic inner branches,
      which are not observed in the K+ channels, appear to have at least as important a
      role as the inner helices for RyR1 gating. We propose a theoretical model whereby
      the inner helices, the inner branches, and the h1 densities together create an
      efficient novel gating mechanism for channel opening by relaxing two right-handed
      bundle structures along a common 4-fold axis.

PMID- 19402749
TI  - Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5
      fluorouracil.
AB  - 5-Fluorouracil (5-FU), a chemotherapeutic drug commonly used in cancer treatment,
      imbalances nucleotide pools, thereby favoring misincorporation of uracil and 5-FU
      into genomic DNA. The processing of these bases by DNA repair activities was
      proposed to cause DNA-directed cytotoxicity, but the underlying mechanisms have
      not been resolved. In this study, we investigated a possible role of thymine DNA
      glycosylase (TDG), one of four mammalian uracil DNA glycosylases (UDGs), in the
      cellular response to 5-FU. Using genetic and biochemical tools, we found that
      inactivation of TDG significantly increases resistance of both mouse and human
      cancer cells towards 5-FU. We show that excision of DNA-incorporated 5-FU by TDG
      generates persistent DNA strand breaks, delays S-phase progression, and activates
      DNA damage signaling, and that the repair of 5-FU-induced DNA strand breaks is
      more efficient in the absence of TDG. Hence, excision of 5-FU by TDG, but not by
      other UDGs (UNG2 and SMUG1), prevents efficient downstream processing of the
      repair intermediate, thereby mediating DNA-directed cytotoxicity. The status of
      TDG expression in a cancer is therefore likely to determine its response to 5-FU
      based chemotherapy.

PMID- 19402747
TI  - Sir2 paralogues cooperate to regulate virulence genes and antigenic variation in
      Plasmodium falciparum.
AB  - Cytoadherance of Plasmodium falciparum-infected erythrocytes in the brain, organs
      and peripheral microvasculature is linked to morbidity and mortality associated
      with severe malaria. Parasite-derived P. falciparum Erythrocyte Membrane Protein
      1 (PfEMP1) molecules displayed on the erythrocyte surface are responsible for
      cytoadherance and undergo antigenic variation in the course of an infection.
      Antigenic variation of PfEMP1 is achieved by in situ switching and mutually
      exclusive transcription of the var gene family, a process that is controlled by
      epigenetic mechanisms. Here we report characterisation of the P. falciparum
      silent information regulator's A and B (PfSir2A and PfSir2B) and their
      involvement in mutual exclusion and silencing of the var gene repertoire.
      Analysis of P. falciparum parasites lacking either PfSir2A or PfSir2B shows that
      these NAD(+)-dependent histone deacetylases are required for silencing of
      different var gene subsets classified by their conserved promoter type. We also
      demonstrate that in the absence of either of these molecules mutually exclusive
      expression of var genes breaks down. We show that var gene silencing originates
      within the promoter and PfSir2 paralogues are involved in cis spreading of
      silenced chromatin into adjacent regions. Furthermore, parasites lacking PfSir2A
      but not PfSir2B have considerably longer telomeric repeats, demonstrating a role
      for this molecule in telomeric end protection. This work highlights the pivotal
      but distinct role for both PfSir2 paralogues in epigenetic silencing of P.
      falciparum virulence genes and the control of pathogenicity of malaria infection.

PMID- 19402750
TI  - Structural studies of the giant mimivirus.
AB  - Mimivirus is the largest known virus whose genome and physical size are
      comparable to some small bacteria, blurring the boundary between a virus and a
      cell. Structural studies of Mimivirus have been difficult because of its size and
      long surface fibers. Here we report the use of enzymatic digestions to remove the
      surface fibers of Mimivirus in order to expose the surface of the viral capsid.
      Cryo-electron microscopy (cryoEM) and atomic force microscopy were able to show
      that the 20 icosahedral faces of Mimivirus capsids have hexagonal arrays of
      depressions. Each depression is surrounded by six trimeric capsomers that are
      similar in structure to those in many other large, icosahedral double-stranded
      DNA viruses. Whereas in most viruses these capsomers are hexagonally close-packed
      with the same orientation in each face, in Mimivirus there are vacancies at the
      systematic depressions with neighboring capsomers differing in orientation by 60
      degrees . The previously observed starfish-shaped feature is well-resolved and
      found to be on each virus particle and is associated with a special pentameric
      vertex. The arms of the starfish fit into the gaps between the five faces
      surrounding the unique vertex, acting as a seal. Furthermore, the enveloped
      nucleocapsid is accurately positioned and oriented within the capsid with a
      concave surface facing the unique vertex. Thus, the starfish-shaped feature and
      the organization of the nucleocapsid might regulate the delivery of the genome to
      the host. The structure of Mimivirus, as well as the various fiber components
      observed in the virus, suggests that the Mimivirus genome includes genes derived
      from both eukaryotic and prokaryotic organisms. The three-dimensional cryoEM
      reconstruction reported here is of a virus with a volume that is one order of
      magnitude larger than any previously reported molecular assembly studied at a
      resolution of equal to or better than 65 Angstroms.

PMID- 19402751
TI  - Structural and functional analyses of PAS domain interactions of the clock
      proteins Drosophila PERIOD and mouse PERIOD2.
AB  - PERIOD proteins are central components of the Drosophila and mammalian circadian
      clocks. The crystal structure of a Drosophila PERIOD (dPER) fragment comprising
      two PER-ARNT-SIM (PAS) domains (PAS-A and PAS-B) and two additional C-terminal
      alpha-helices (alphaE and alphaF) has revealed a homodimer mediated by
      intermolecular interactions of PAS-A with tryptophane 482 in PAS-B and helix
      alphaF. Here we present the crystal structure of a monomeric PAS domain fragment
      of dPER lacking the alphaF helix. Moreover, we have solved the crystal structure
      of a PAS domain fragment of the mouse PERIOD homologue mPER2. The mPER2 structure
      shows a different dimer interface than dPER, which is stabilized by interactions
      of the PAS-B beta-sheet surface including tryptophane 419 (equivalent to
      Trp482dPER). We have validated and quantitatively analysed the homodimer
      interactions of dPER and mPER2 by site-directed mutagenesis using analytical gel
      filtration, analytical ultracentrifugation, and co-immunoprecipitation
      experiments. Furthermore we show, by yeast-two-hybrid experiments, that the PAS-B
      beta-sheet surface of dPER mediates interactions with TIMELESS (dTIM). Our study
      reveals quantitative and qualitative differences between the homodimeric PAS
      domain interactions of dPER and its mammalian homologue mPER2. In addition, we
      identify the PAS-B beta-sheet surface as a versatile interaction site mediating
      mPER2 homodimerization in the mammalian system and dPER-dTIM heterodimer
      formation in the Drosophila system.

PMID- 19402752
TI  - Reawakening retrocyclins: ancestral human defensins active against HIV-1.
AB  - Human alpha and beta defensins contribute substantially to innate immune defenses
      against microbial and viral infections. Certain nonhuman primates also produce
      theta-defensins-18 residue cyclic peptides that act as HIV-1 entry inhibitors.
      Multiple human theta-defensin genes exist, but they harbor a premature
      termination codon that blocks translation. Consequently, the theta-defensins
      (retrocyclins) encoded within the human genome are not expressed as peptides. In
      vivo production of theta-defensins in rhesus macaques involves the post
      translational ligation of two nonapeptides, each derived from a 12-residue
      "demidefensin" precursor. Neither the mechanism of this unique process nor its
      existence in human cells is known. To ascertain if human cells retained the
      ability to process demidefensins, we transfected human promyelocytic cells with
      plasmids containing repaired retrocyclin-like genes. The expected peptides were
      isolated, their sequences were verified by mass spectrometric analyses, and their
      anti-HIV-1 activity was confirmed in vitro. Our study reveals for the first time,
      to our knowledge, that human cells have the ability to make cyclic theta
      defensins. Given this evidence that human cells could make theta-defensins, we
      attempted to restore endogenous expression of retrocyclin peptides. Since human
      theta-defensin genes are transcribed, we used aminoglycosides to read-through the
      premature termination codon found in the mRNA transcripts. This treatment induced
      the production of intact, bioactive retrocyclin-1 peptide by human epithelial
      cells and cervicovaginal tissues. The ability to reawaken retrocyclin genes from
      their 7 million years of slumber using aminoglycosides could provide a novel way
      to secure enhanced resistance to HIV-1 infection.

PMID- 19402753
TI  - Global functional atlas of Escherichia coli encompassing previously
      uncharacterized proteins.
AB  - One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain
      functionally unannotated (orphans). Many map to distant clades such as Archaea,
      suggesting involvement in basic prokaryotic traits, whereas others appear
      restricted to E. coli, including pathogenic strains. To elucidate the orphans'
      biological roles, we performed an extensive proteomic survey using affinity
      tagged E. coli strains and generated comprehensive genomic context inferences to
      derive a high-confidence compendium for virtually the entire proteome consisting
      of 5,993 putative physical interactions and 74,776 putative functional
      associations, most of which are novel. Clustering of the respective probabilistic
      networks revealed putative orphan membership in discrete multiprotein complexes
      and functional modules together with annotated gene products, whereas a machine
      learning strategy based on network integration implicated the orphans in specific
      biological processes. We provide additional experimental evidence supporting
      orphan participation in protein synthesis, amino acid metabolism, biofilm
      formation, motility, and assembly of the bacterial cell envelope. This resource
      provides a "systems-wide" functional blueprint of a model microbe, with insights
      into the biological and evolutionary significance of previously uncharacterized
      proteins.

PMID- 19402754
TI  - Identification of human S100A9 as a novel target for treatment of autoimmune
      disease via binding to quinoline-3-carboxamides.
AB  - Despite more than 25 years of research, the molecular targets of quinoline-3
      carboxamides have been elusive although these compounds are currently in Phase II
      and III development for treatment of autoimmune/inflammatory diseases in humans.
      Using photoaffinity cross-linking of a radioactively labelled quinoline-3
      carboxamide compound, we could determine a direct association between human
      S100A9 and quinoline-3-carboxamides. This interaction was strictly dependent on
      both Zn++ and Ca++. We also show that S100A9 in the presence of Zn++ and Ca++ is
      an efficient ligand of receptor for advanced glycation end products (RAGE) and
      also an endogenous Toll ligand in that it shows a highly specific interaction
      with TLR4/MD2. Both these interactions are inhibited by quinoline-3-carboxamides.
      A clear structure-activity relationship (SAR) emerged with regard to the binding
      of quinoline-3-carboxamides to S100A9, as well as these compounds potency to
      inhibit interactions with RAGE or TLR4/MD2. The same SAR was observed when the
      compound's ability to inhibit acute experimental autoimmune encephalomyelitis in
      mice in vivo was analysed. Quinoline-3-carboxamides would also inhibit TNFalpha
      release in a S100A9-dependent model in vivo, as would antibodies raised against
      the quinoline-3-carboxamide-binding domain of S100A9. Thus, S100A9 appears to be
      a focal molecule in the control of autoimmune disease via its interactions with
      proinflammatory mediators. The specific binding of quinoline-3-carboxamides to
      S100A9 explains the immunomodulatory activity of this class of compounds and
      defines S100A9 as a novel target for treatment of human autoimmune diseases.

PMID- 19402755
TI  - Specificity and plasticity of thalamocortical connections in Sema6A mutant mice.
AB  - The establishment of connectivity between specific thalamic nuclei and cortical
      areas involves a dynamic interplay between the guidance of thalamocortical axons
      and the elaboration of cortical areas in response to appropriate innervation. We
      show here that Sema6A mutants provide a unique model to test current ideas on the
      interactions between subcortical and cortical guidance mechanisms and cortical
      regionalization. In these mutants, axons from the dorsal lateral geniculate
      nucleus (dLGN) are misrouted in the ventral telencephalon. This leads to invasion
      of presumptive visual cortex by somatosensory thalamic axons at embryonic stages.
      Remarkably, the misrouted dLGN axons are able to find their way to the visual
      cortex via alternate routes at postnatal stages and reestablish a normal pattern
      of thalamocortical connectivity. These findings emphasize the importance and
      specificity of cortical cues in establishing thalamocortical connectivity and the
      spectacular capacity of the early postnatal cortex for remapping initial sensory
      representations.

PMID- 19402757
TI  - Specific in vitro toxicity of crude and refined petroleum products. 1. Aryl
      hydrocarbon receptor-mediated responses.
AB  - The present study is the first in a series reporting on in vitro toxic potencies
      of oils. The objective was to determine whether 11 crude oils and refined
      products activate the aryl hydrocarbon receptor (AhR) in a dioxin receptor
      mediated luciferase assay. Cells were exposed for 6 and 24 h to different oil
      concentrations to screen for polycyclic aromatic hydrocarbon-like or dioxin-like
      activity. Moreover, cytotoxicity of the oils was determined using rat hepatoma
      cells. Except for one crude oil, none of the oils appeared cytotoxic up to 100
      mg/L, but all oils activated the AhR. Strong AhR induction was observed for most
      oils after 6 h, and responses decreased after 24 h, indicating the presence of
      metabolizable agonists. However, several oils still caused high responses after
      24 h, also demonstrating the presence of persistent agonists. The potencies
      (calculated based on comparisons of concentrations at which 50% of the maximal
      effect was observed) of oils were found to be approximately 40 to 106 times lower
      than the potency of the assay's standards benzo[a]pyrene and 2,3,7,8
      tetrachlorodibenzo-p-dioxin. However, considering that oils contain thousands of
      chemicals, the potencies of petrochemical agonists may be very high. Among the
      most potent oils were bunker and crude oils. Induction up to 200% as compared to
      the maximum induction caused by benzo[a]pyrene was observed for these oils. Such
      supermaximal responses suggest mixture effects that may not be receptor-mediated.
      Experiments in which oils were tested in combination with the standards
      demonstrated that oils acted via an antagonistic or additive mode. The results of
      the present study may help improve risk assessment of petroleum products and
      judge the necessity or priority of oil spill cleanup activities.

PMID- 19402758
TI  - Gene expression analysis in zebrafish embryos: a potential approach to predict
      effect concentrations in the fish early life stage test.
AB  - Based on the hypothesis that analysis of gene expression could be used to predict
      chronic fish toxicity, the zebrafish (Danio rerio) embryo test (DarT), developed
      as a replacement method for the acute fish test, was expanded to a gene
      expression D. rerio embryo test (Gene-DarT). The effects of 14 substances on
      lethal and sublethal endpoints of the DarT and on expression of potential marker
      genes were investigated: the aryl hydrocarbon receptor 2, cytochrome P450 1A
      (cypla), heat shock protein 70, fizzy-related protein 1, the transcription
      factors v-maf musculoaponeurotic fibrosarcoma oncogene family protein g (avian) 1
      and NF-E2-p45-related factor, and heme oxygenase 1 (hmox1). After exposure of
      zebrafish embryos for 48 h, differential gene expression was evaluated using
      reverse transcriptase-polymerase chain reaction, gel electrophoresis, and
      densitometric analysis of the gels. All tested compounds significantly affected
      the expression of at least one potential marker gene, with cyp1a and hmox1 being
      most sensitive. Lowest-observed-effect concentrations (LOECs) for gene expression
      were below concentrations resulting in 10% lethal effects in the DarT. For 10
      (3,4- and 3,5-dichloroaniline, 1,4-dichlorobenzene, 2,4-dinitrophenol, atrazine,
      parathion-ethyl, chlorotoluron, genistein, 4-nitroquinoline-1-oxide, and cadmium)
      out of the 14 tested substances, LOEC values derived with the Gene-DarT differ by
      a factor of less than 10 from LOEC values of fish early life stage tests with
      zebrafish. For pentachloroaniline and pentachlorobenzene, the Gene-DarT showed a
      23- and 153-fold higher sensitivity, respectively, while for lindane, it showed a
      13-fold lower sensitivity. For ivermectin, the Gene-DarT was by a factor of more
      than 1,000 less sensitive than the acute fish test. The results of the present
      study indicate that gene expression analysis in zebrafish embryos could
      principally be used to predict effect concentrations in the fish early life stage
      test.

PMID- 19402759
TI  - There should be more help out here! A qualitative study of the needs of
      Aboriginal adolescents in rural Australia.
AB  - INTRODUCTION: Aboriginal adolescents living in or near rural towns have different
      social and cultural needs than Aboriginal adolescents living in large cities or
      remote areas. Identification of health needs by the community is an established
      principle of health promotion for improving community health. The objective of
      this study was to identify the views of rural Aboriginal adolescents regarding
      health promotion topics, the most important health problems they faced, their
      support networks and their beliefs about who should help them meet their health
      needs. METHODS: Ninety-nine adolescents aged between 12 and 18 years were
      involved in in-depth interviews or focus group discussions using a tested and
      trialled questionnaire. Data collection took place at three sites in rural
      Australia from 2006 to 2008: two Aboriginal-controlled communities and one rural
      town. All locations were de-identified at the request of participants because
      confidentiality and anonymity were concerns of the adolescents, who felt that
      identifying their own community would result in stereotyping. After preliminary
      interviews with parents, teachers, youth and health workers, snowball sampling
      was used to identify 'vulnerable' adolescents with low school attendance. The
      mean age of respondents was 13 years. There were 40 male participants and 59
      female participants, representing 6 language groups. Informed consent was
      obtained from both participants and their guardians. Data were analysed using
      thematic matrices and cross-checked in subsequent interactions with participants.
      RESULTS: Alcohol, drugs and violence were identified as the biggest problems
      facing Aboriginal adolescents in rural areas and the topic they would most like
      to know about. The youth from a smaller Aboriginal community near a town with a
      population of 1500 stated that boredom was an equally important problem. Racism
      and bullying were noted as reasons for poor school attendance. Family members
      were the most important supports, and the people they felt would help solve their
      health problems. They strongly identified with sports and were proud to be
      Aboriginal although there were many adolescents who had no future plans or
      ambitions. Most participants wanted a 'safe and fun' place to go to in the
      evenings. CONCLUSIONS: The importance of engaging the community and being
      sensitive to social and cultural contexts in research and programming was
      confirmed. Policy-makers, health providers and agencies working with youth need
      to focus on inclusion of families in youth health promotion and drug and alcohol
      prevention for Aboriginal adolescents in rural areas. Mentorship and peer-support
      programs are more effective than health professionals and agencies in working
      with youth. The expertise of those traditionally working with youth could be
      channelled into coordinating a mentorship program. Personal wellbeing and safety
      is an important issue and multipurpose youth centres may provide a secure place
      for adolescents to learn, interact and develop a vision for their futures.

PMID- 19402760
TI  - Ecology of the Crimean-Congo hemorrhagic fever endemic area in Albania.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Albania. Ticks
      collected from cattle grazing in the endemic areas of Albania were tested for
      presence of CCHFV RNA, while serum samples collected from goats, cattle, hares,
      and birds were tested for the presence of specific IgG antibodies to CCHFV. One
      of the 31 pools prepared, consisting of four female Hyalomma spp. ticks, was
      found to carry CCHFV RNA with 99.2-100% homology to sequences detected in
      patients from the same region. Antibodies were not detected in cattle, hares, and
      birds, but 2/10 goats presented high titers of IgG antibodies. The shepherd of
      that flock was a member of a family affected by CCHF 10 days before the
      collection of goats' sera, and he presented a mild form of the disease.

PMID- 19402761
TI  - Serological surveillance of scrub typhus, murine typhus, and leptospirosis in
      small mammals captured at firing points 10 and 60, Gyeonggi province, Republic of
      Korea, 2001-2005.
AB  - Soldiers from the Republic of Korea and the United States conducting peacetime
      military operations at various training sites and multiple range complexes
      located near the demilitarized zone separating North and South Korea are exposed
      to rodents and their potentially disease-carrying ectoparasites. These diseases
      include scrub typhus, murine typhus, and leptospirosis. Many of the training
      sites are rural or semi-rural, surrounded or co-located with various forms of
      agriculture, and are infested with rodents and insectivores (as well as their
      ectoparasites), which are commonly found in association with unmanaged tall
      grasses, scrub, and crawling vegetation habitats. For 5 years, rodents and
      insectivores were collected seasonally (spring, summer, fall, and winter) at
      firing points 10 and 60 near the demilitarized zone and serologically tested for
      the presence of scrub typhus, murine typhus, and leptospirosis antibodies. Of the
      nine species of small mammals collected, Apodemus agrarius, the common striped
      field mouse and known reservoir of scrub typhus, was the most frequently
      collected (90.6%). Only four of the nine species captured, A. agrarius (60.9%),
      Micromys minutus (100%), Mus musculus (55.6%), and Rattus norvegicus (46.7%),
      were positive for scrub typhus. Of all the small mammals captured, only A.
      agrarius was positive for murine typhus (0.3%) and leptospirosis (1.3%). Seasonal
      and annual prevalence rates based on weight and sex are presented.

PMID- 19402756
TI  - Abl kinase inhibits the engulfment of apoptotic [corrected] cells in
      Caenorhabditis elegans.
AB  - The engulfment of apoptotic cells is required for normal metazoan development and
      tissue remodeling. In Caenorhabditis elegans, two parallel and partially
      redundant conserved pathways act in cell-corpse engulfment. One pathway includes
      the adaptor protein CED-2 CrkII and the small GTPase CED-10 Rac, and acts to
      rearrange the cytoskeleton of the engulfing cell. The other pathway includes the
      receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface
      of the engulfing cell. Although many components required for engulfment have been
      identified, little is known about inhibition of engulfment. The tyrosine kinase
      Abl regulates the actin cytoskeleton in mammals and Drosophila in multiple ways.
      For example, Abl inhibits cell migration via phosphorylation of CrkII. We tested
      whether ABL-1, the C. elegans ortholog of Abl, inhibits the CED-2 CrkII-dependent
      engulfment of apoptotic cells. Our genetic studies indicate that ABL-1 inhibits
      apoptotic cell engulfment, but not through CED-2 CrkII, and instead acts in
      parallel to the two known engulfment pathways. The CED-10 Rac pathway is also
      required for proper migration of the distal tip cells (DTCs) during the
      development of the C. elegans gonad. The loss of ABL-1 function partially
      restores normal DTC migration in the CED-10 Rac pathway mutants. We found that
      ABI-1 the C. elegans homolog of mammalian Abi (Abl interactor) proteins, is
      required for engulfment of apoptotic cells and proper DTC migration. Like Abl,
      Abi proteins are cytoskeletal regulators. ABI-1 acts in parallel to the two known
      engulfment pathways, likely downstream of ABL-1. ABL-1 and ABI-1 interact
      physically in vitro. We propose that ABL-1 opposes the engulfment of apoptotic
      cells by inhibiting ABI-1 via a pathway that is distinct from the two known
      engulfment pathways.

PMID- 19402763
TI  - Identification of a Bartonella species in the harbor seal (Phoca vitulina) and in
      seal lice (Echinophtirius horridus).
AB  - To explore whether harbor seals (Phoca vitulina) are exposed to Bartonella spp.,
      35 seal lice (Echinophtirius horridus) were collected from seven seals, during
      their rehabilitation period in the Seal Rehabilitation and Research Center at
      Pieterburen, The Netherlands. Forty-eight spleen samples were collected during
      necropsies of other harbor seals that died during rehabilitation, or had stranded
      dead and were brought to the Seal Rehabilitation and Research Center for
      postmortem investigation. Lice were grouped into six pools, and DNA was extracted
      from each pool and from all the seals' spleen samples. One of the six lice pools
      and one spleen sample were found positive by high-resolution melt, real-time PCR
      amplifying partial loci of the rpoB gene, and the intergenic spacer (ITS) region.
      The Bartonella spp. identified in the spleen and lice were found to be identical
      to each other. One hundred percent sequence similarity with Bartonella henselae
      was found in the ITS, and 97% sequence similarity with Bartonella grahamii was
      detected in the rpoB gene. To the best of the authors' knowledge, this is the
      first report describing the detection of Bartonella spp. from a seal or any other
      pinniped, and from seal lice, E. horridus. The 100% sequence similarity in the
      ITS of the Bartonella sp. identified with the zoonotic B. henselae warrants
      further investigation and characterization of this organism, which may be found
      to be of public health importance.

PMID- 19402762
TI  - A longitudinal study of the prevalence of Nipah virus in Pteropus lylei bats in
      Thailand: evidence for seasonal preference in disease transmission.
AB  - After 12 serial Nipah virus outbreaks in humans since 1998, it has been noted
      that all except the initial event in Malaysia occurred during the first 5 months
      of the year. Increasingly higher morbidity and mortality have been observed in
      subsequent outbreaks in India and Bangladesh. This may have been related to
      different virus strains and transmission capability from bat to human without the
      need for an amplifying host and direct human-to-human transmission. A survey of
      virus strains in Pteropus lylei and seasonal preference for spillover of these
      viruses was completed in seven provinces of Central Thailand between May 2005 and
      June 2007. Nipah virus RNA sequences, which belonged to those of the Malaysian
      and Bangladesh strains, were detected in the urine of these bats, with the
      Bangladesh strain being dominant. Highest recovery of Nipah virus RNA was
      observed in May. Of two provincial sites where monthly surveys were done, the
      Bangladesh strain was almost exclusively detected during April to June. The
      Malaysian strain was found dispersed during December to June. Although direct
      contact during breeding (in December to April) was believed to be an important
      transmission factor, our results may not entirely support the role of breeding
      activities in spillage of virus. Greater virus shedding over extended periods in
      the case of the Malaysian strain and the highest peak of virus detection in May
      in the case of the Bangladesh strain when offspring started to separate may
      suggest that there may be responsible mechanisms other than direct contact during
      breeding in the same roost. Knowledge of seasonal preferences of Nipah virus
      shedding in P. lylei will help us to better understand the dynamics of Nipah
      virus transmission and have implications for disease management.

PMID- 19402764
TI  - Trichinellosis, a threatening and re-emerging disease in a Romanian western
      county.
AB  - INTRODUCTION: Trichinellosis is frequently reported in east European countries
      like Romania, where the yearly incidence during 1990-1999 was 5.5 cases/100,000
      inhabitants. Arad, a western Romanian county, is known as one of the most endemic
      regions of trichinellosis. A major and unforgettable epidemic of trichinellosis
      has developed at the beginning of 1973 in this county. The present study focuses
      on human trichinellosis patients from Arad County, emphasizing on
      epidemiological, clinical, laboratory, and therapeutic aspects. PATIENTS AND
      METHODS: Retrospective analysis of the medical records of 335 patients found to
      have trichinellosis during 1996-2006 and hospitalized in Arad County. The mean
      age of the trichinellosis patients was 33.6 years, and majority (64.8%) were
      inhabitants of the rural areas. RESULTS: Winter was the season with the highest
      number of cases (71.6%). Fever was the most frequent manifestation of the disease
      (85.4%), followed by myalgia (83%). Eosinophilia ranged predominantly between 20%
      and 20.99% (19.4%). Albendazole was the specific drug administered in 49.4% of
      the patients. CONCLUSIONS: Trichinellosis still remains a concern and a major
      issue of public health in Arad County. Implementation of strict hygienic
      measures, especially in the rural areas, must be a priority.

PMID- 19402765
TI  - Susceptibility of fox squirrels (Sciurus niger) to West Nile virus by oral
      exposure.
AB  - Fox squirrels (Sciurus niger) (five of eight) were infected with West Nile virus
      (WNV) when challenged by the oral route with 10(2.3) or 10(3.4) plaque forming
      units (PFU). The mean maximum serum WNV titer of infected fox squirrels was
      10(5.1) PFU/mL and ranged from 10(4.6) to 10(5.6) PFU/mL. These levels of viremia
      are infectious for several mosquito vectors of WNV. This virus was also isolated
      from swabs of the oral and rectal cavities, and urine swabs between day 5 and 9
      postexposure (p.e.) in amounts as high as 10(2.0), 10(2.8), and 10(2) PFU,
      respectively. WNV RNA was detected in salivary gland and/or kidney tissue of
      three squirrels between day 65 and 72 p.e. in the presence of WNV neutralizing
      antibody, suggesting that long-term persistent infection occurs in fox squirrels.
      These observations justify further studies to determine if nonarthropod
      transmission and long-term persistent infection occur naturally in fox squirrels
      and contribute to trans-seasonal maintenance of WNV.

PMID- 19402766
TI  - Low West Nile virus circulation in wild birds in an area of recurring outbreaks
      in Southern France.
AB  - West Nile virus (WNV) has a history of irregular but recurrent epizootics in
      countries of Mediterranean and of Central and Eastern Europe. We have
      investigated the temporal enzootic activity of WNV in free-ranging birds over a 3
      year period in an area with sporadic occurrences of WNV outbreaks in Southern
      France. We conducted an intensive serologic survey on several wild bird
      populations (>4000 serum samples collected from 3300 birds) selected as potential
      indicators of the WNV circulation. WNV antibodies were detected by
      seroneutralization and/or plaque reduction neutralization in house sparrows,
      black-billed magpies, and scops owls, but these species appeared to be
      insufficient indicators of WNV circulation. Overall seroprevalence was low (<1%),
      including in birds that had been potentially exposed to the virus during recent
      outbreaks. However, the detection of a seroconversion in one bird, as well as the
      detection of seropositive birds in all years of our monitoring, including
      juveniles, indicate a constant annual circulation of WNV at a low level,
      including in years without any detectable emergence of WN fever in horses or
      humans.

PMID- 19402767
TI  - Enzootic activity of pixuna and Rio Negro viruses (Venezuelan equine encephalitis
      complex) in a neotropical region of Argentina.
AB  - Venezuelan Equine Encephalitis complex viruses cause epidemics and epizootics
      periodically in some regions of the Americas. In Argentina, only enzootic Rio
      Negro virus (AG80-663) (RNV) has been isolated. To survey and identify activity
      of viruses that belong to Venezuelan Equine Encephalitis complex in a template
      region of the country, a generic Alphavirus RT-Nested PCR was performed in 99
      mosquito pools collected in Chaco province. Five pools were positive, and
      amplicons were sequenced: four of them clustered with RNV(AG80-663) and one with
      Pixuna virus. This is the first report of the circulation of Pixuna virus in
      Argentina, and it confirms enzootic and endemic activity of RNV(AG80-663) in
      neotropical regions of this country.

PMID- 19402768
TI  - Carnosine, diabetes and Alzheimer's disease.

PMID- 19402770
TI  - Donepezil in the treatment of patients with Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia and is
      characterized by an insidious onset and slow deterioration in cognition,
      activities of daily living (ADL), mood stability and social functioning. The
      cholinesterase inhibitors (ChEIs), developed based on the cholinergic hypothesis,
      are currently considered to be the best established treatment for AD, although
      the significant advances in the symptomatic pharmacotherapy of AD may be followed
      by disease-modification treatments. Donepezil is a mixed competitive and
      noncompetitive acetylcholinesterase inhibitor that shows a relative selectivity
      for acetylcholinesterase inhibitor compared with butyrylcholinesterase. In many
      clinical trials of donepezil, beneficial effects on standard measures of
      cognitive function, ADL and behavior have been shown in patients with mild,
      moderate or severe AD. Although the pharmacological and phamacokinetic profiles
      of the currently available ChEIs have notable differences that may affect
      efficacy, the clinical significance of these differences remains hypothetical in
      the absence of large, randomized trials that compare the ChEIs with each other.

PMID- 19402771
TI  - Sugammadex: a selective relaxant binding agent for reversal of neuromuscular
      block.
AB  - Neostigmine, the currently used agent for reversal of neuromuscular block, has
      several drawbacks, such as a slow onset of peak effect, inability to reverse deep
      block and the occurrence of widespread muscarinic effects. Sugammadex is a new
      class of reversal agent that acts by encapsulating the molecules of the relaxants
      rocuronium and vecuronium, for which it is a specific antagonist. Clinical trials
      in over 2000 subjects have shown it to be effective for reversal of block by
      these two relaxants even from deep levels, in doses of 2.0-4.0 mg/kg. Sugammadex
      can also reverse an intense (profound) high-dose rocuronium block, but the dose
      required in this situation is 16.0 mg/kg. The agent has been found to be safe so
      far, with few side effects.

PMID- 19402773
TI  - Metabolic links between diabetes and Alzheimer's disease.
AB  - There is a cluster of risk factors for Type 2 diabetes and vascular disease that
      include high blood glucose, obesity, high blood pressure, increased blood
      triacylglycerols and insulin resistance. All of these factors, both individually
      and collectively, increase the risk of Alzheimer's disease (AD) and vascular
      dementia. Alterations in insulin signaling, glucose and fatty acid metabolism, as
      well as the accumulation of oxidatively modified and glycated proteins, are
      associated with both diabetes and the dementias. Data from animal and cell
      culture models have shown that there is a synergistic interaction between most of
      these stresses in both AD and diabetes, and with the elevated beta-amyloid
      peptide levels that are also linked to AD. Some of these parameters can be
      modified by diet and others may require novel drugs. However, because of the
      multiplicity of physiological pathways involved, conventional drug therapies
      directed against a single target are not going to be effective in treating AD or
      the complications of diabetes. It is therefore likely that the only successful
      therapy will involve the use of drugs with multiple targets in concert with
      changes in diet and lifestyle.

PMID- 19402772
TI  - Buprenorphine for opioid dependence.
AB  - As a treatment agent for opioid dependence, buprenorphine is a nearly ideal
      medication at our current stage of medication development. Unlike methadone,
      buprenorphine dosage can be rapidly adjusted with minimal potential for inducing
      severe consequences. In addition to its intrinsic safety, buprenorphine's
      relatively low abuse liability in the combination product (i.e., with naloxone as
      Suboxone) makes it even more acceptable in regulatory quarters as well as to
      prescribing physicians. The approval of buprenorphine as a pharmacotherapy for
      opioid dependence returns to physicians the ability to treat their opioid
      dependent patients with an effective opioid-based treatment for the first time in
      nearly 100 years. Buprenorphine is an opioid, however, and potential for misuse
      remains, even in combination with naloxone. Whether buprenorphine will be
      increasingly accepted as a treatment for opioid-dependent patients depends on
      clinicians recognizing the advantages of its uniquely useful properties while
      still heeding the need to manage their patients' therapy with reasonable
      vigilance.

PMID- 19402774
TI  - Copper in Alzheimer's disease: too much or too little?
AB  - A considerable amount of literature has accrued examining the role of copper in
      the pathogenesis of Alzheimer's disease. Remarkably, there is in vitro and animal
      data to support both copper toxicity and copper deficiency as relevant mechanisms
      in Alzheimer's disease. These data have prompted preliminary clinical trials of
      both copper complexing therapy and copper supplementation therapy, which have
      yielded mixed results. The preclinical and clinical studies are discussed here in
      an effort to determine how to move forward with rational clinical trials focused
      on copper modulation.

PMID- 19402775
TI  - Pediatric stroke guidelines: where will these take future research and treatment
      options for childhood stroke?
AB  - Stroke is as common as brain tumor in children and results in long-term morbidity
      in at least two thirds of survivors. There has been a recent explosion of
      research in the field of childhood stroke, reflected in the publication of three
      sets of clinical guidelines, two within the last year. However, there is still a
      poor evidence base underpinning recommendations relating to investigation and
      treatment of childhood stroke, which need to be specific to the vascular stroke
      syndrome in question, as well as to the age of the affected child. Acute stroke
      is still under-recognized in children and there is a role for educating
      healthcare professionals. Improved precision in categorization as well as
      investigation of disease mechanisms and treatments specific to childhood stroke,
      rather than extrapolation from research in adults, are essential next steps.
      Consortia, such as the International Pediatric Stroke Study group, will provide
      vital infrastructure for such work.

PMID- 19402776
TI  - The triptans.
AB  - The migraine-specific triptans have revolutionized the treatment of migraine and
      are currently the drugs of choice to treat a migraine attack in progress. Over
      the past 15 years, triptans were released in rapid succession, with each one
      demonstrating some specific pharmacokinetic properties that may be translated
      into clinical advantages. Triptans share many similarities, but also have
      important differences from one another. Accordingly, herein we discuss the class
      of the triptans. We first define the trigeminovascular system and its importance
      in migraine pain, then discuss the mechanism of action of the triptans and
      contrast the evidence supporting the use of different triptans. We close with our
      view of the future and hopes for the next generation of antimigraine therapies.

PMID- 19402777
TI  - Secretase inhibitors and modulators for Alzheimer's disease treatment.
AB  - Genetic and biological studies provide strong evidence that the deposition of
      amyloid-beta peptide (Abeta) contributes to the etiology of Alzheimer's disease
      (AD). Abeta is generated from amyloid-beta precursor protein by beta- and gamma
      secretases, which are plausible molecular targets for AD treatment. Thus, drugs
      that regulate the production of Abeta by inhibiting or modulating secretase
      activity could provide effective therapeutics for AD. Both secretases are
      transmembrane proteases: beta-site amyloid-beta precursor protein cleaving enzyme
      1, the main neuronal beta-secretase, is a single span transmembrane aspartyl
      protease; gamma-secretase is a multiprotein complex comprising four core subunits
      that are all transmembrane proteins: presenilin, nicastrin, anterior pharynx
      defective 1 and presenilin enhancer 2. Molecular biochemical, enzymological and
      genetic analyses reveal the molecular mechanisms of these secretases in the
      generation of Abeta. Moreover, extensive drug screening and development have
      enabled some secretase inhibitors and modulators to advance into late-Phase
      clinical trials. This review focuses on recent progresses in beta- and gamma
      secretase biology, including the proteolytic mechanism, regulation and
      composition of these enzymes. Moreover, this review discusses the recent
      development of inhibitors, and provides a direction for the effective treatment
      of AD through inhibition/modulation of beta- and gamma-secretase activities.

PMID- 19402778
TI  - Calcium dyshomeostasis and neurotoxicity of Alzheimer's beta-amyloid protein.
AB  - Neurotoxicity of Alzheimer's beta-amyloid protein (AbetaP) is central to the
      pathogenesis of Alzheimer's disease (AD). Recent approaches have emphasized the
      importance of AbetaP oligomerization, which causes synaptic degeneration and
      neuronal loss, finally leading to the pathogenesis of AD. Although the precise
      molecular mechanism of AbetaP neurotoxicity remains elusive, our and other
      numerous findings have demonstrated that AbetaP directly incorporated into
      neuronal membranes formed calcium-permeable ion channels (amyloid channels) and
      resulted in an abnormal elevation of the intracellular calcium levels. The
      formation of amyloid channels and the abnormal increase of intracellular Ca(2+)
      have also been commonly observed in other neurodegenerative diseases, including
      conformational diseases such as prion disease or dementia with Lewy bodies. This
      article reviews the current understanding of the pathology of AD based on the
      hypothesis that the disruption of calcium homeostasis through amyloid channels
      may be the molecular basis of AbetaP neurotoxicity. The potential development of
      preventive agents is also discussed.

PMID- 19402779
TI  - Cholesterol-modifying strategies for Alzheimer's disease.
AB  - The link between cholesterol and Alzheimer's disease (AD) is indicated by
      genetic, epidemiological, experimental and clinical evidence, although the
      relationship is far from simple or straightforward. Compared with extracerebral
      cholesterol, little is known about brain cholesterol homeostasis. In addition,
      current diagnostic criteria for AD exclude a priori the pathogenic participation
      of vascular factors (to which cholesterol is traditionally associated), and
      require modifications. Randomized controlled trials suggest that the dementia
      stage of AD may already be too late for significant benefits of statin therapy,
      emphasizing the importance of early diagnosis and treatment. Cholesterol
      modifying strategies may be more effective in dementia/AD prevention. Since
      cholesterol is only one piece of the dementia/AD puzzle, integrative
      interventions (lifestyle-related and, when necessary, pharmacologic) focusing on
      overall risk instead of individual risk factors may bring more benefit to
      individuals at risk.

PMID- 19402780
TI  - Post-stroke pain.
AB  - Pain is one of the most troublesome sequelae of stroke, occurring in 19-74% of
      patients. A portion of this post-stroke pain is caused by the brain lesion
      itself; this is called 'central post-stroke pain' (CPSP). Although the prevalence
      of CPSP among stroke patients is low (1-8%), the persistent, often treatment
      refractory, painful sensations can be a major problem, decreasing the affected
      patient's quality of life. As the aging population continues to increase, CPSP
      will become an even more important problem in the future. Although the
      pathogenesis of CPSP is not yet known, it has been suggested that underlying
      causes include hyperexcitation in the damaged sensory pathways, damage to the
      central inhibitory pathways, or a combination of the two. Adrenergic
      antidepressants are currently the first-line drugs for CPSP, but their effect is
      frequently incomplete. Antiepileptics, such as lamotrigine, can be used as an
      adjunctive therapy, while GABAergic drugs, such as gabapentin or pregabalin, have
      recently emerged as a potentially useful therapy. Nonpharmacological treatments,
      such as motor cortex stimulation or deep brain stimulation, also appear to be
      useful in a certain group of patients. Additional studies are urgently needed to
      improve our understanding of the pathophysiology of CPSP and support the
      development of better treatment modalities.

PMID- 19402781
TI  - Transition from acute to chronic postsurgical pain: risk factors and protective
      factors.
AB  - Most patients who undergo surgery recover uneventfully and resume their normal
      daily activities within weeks. Nevertheless, chronic postsurgical pain develops
      in an alarming proportion of patients. The prevailing approach of focusing on
      established chronic pain implicitly assumes that information generated during the
      acute injury phase is not important to the subsequent development of chronic
      pain. However, a rarely appreciated fact is that every chronic pain was once
      acute. Here, we argue that a focus on the transition from acute to chronic pain
      may reveal important cues that will help us to predict who will go on to develop
      chronic pain and who will not. Unlike other injuries, surgery presents a unique
      set of circumstances in which the precise timing of the physical insult and
      ensuing pain are known in advance. This provides an opportunity, before surgery,
      to identify the risk factors and protective factors that predict the course of
      recovery. In this paper, the epidemiology of chronic postsurgical pain is
      reviewed. The surgical, psychosocial, socio-environmental and patient-related
      factors that appear to confer a greater risk of developing chronic postsurgical
      pain are described. The genetics of chronic postsurgical pain are discussed with
      emphasis on known polymorphisms in human genes associated with chronic pain,
      genetic studies of rodent models of pain involving surgical approaches, the
      importance of developing accurate human chronic postsurgical pain phenotypes and
      the expected gains for chronic postsurgical pain medicine in the post-genomic
      era. Evidence is then reviewed for a preventive multimodal analgesic approach to
      surgery. While there is some evidence that chronic postsurgical pain can be
      minimized or prevented by an analgesic approach involving aggressive
      perioperative multimodal treatment, other studies fail to show this benefit. The
      transition of acute postoperative pain to chronic postsurgical pain is a complex
      and poorly understood developmental process, involving biological, psychological
      and social-environmental factors.

PMID- 19402783
TI  - Brain-evoked potentials as a tool for diagnosing neuropathic pain.
AB  - Neuropathic pain is a complex subject, not completely understood yet, and it is
      quite common in clinical practice, even outside of a neurological context.
      Neuropathic pain, often being a chronic process, alters and profoundly affects
      the quality of life. Therefore, the management of neuropathic pain involves a
      multidimensional approach, as physicians have to take care not only of the
      objective aspects of the problem, but also of the subjective experiences of pain.
      This explains why the attainment of a diagnosis becomes so important, as it
      allows clinicians to treat the patients with the best therapeutic approach.
      Several studies report the use of brain-evoked potentials for studying patients
      suffering from neuropathic pain. In particular, laser- and contact heat-evoked
      potentials have proved useful for the diagnosis of clinical conditions
      characterized by neuropathic pain. However, although these tools are reliable and
      safe instruments to assess function of the nociceptive system, their use is still
      largely confined to research purposes.

PMID- 19402785
TI  - Encapsulation of mesenchymal stem cells from Wharton's jelly in alginate
      microbeads.
AB  - The description of a microencapsulation procedure for Wharton's jelly mesenchymal
      stem cells (WJMSCs) is reported. The applied method is based on the generation of
      monodisperse droplets by a vibrational nozzle. An ionic alginate encapsulation
      procedure was utilized for the microbeads hardening. Different experimental
      parameters were analyzed, including frequency and amplitude of vibration, polymer
      pumping rate, and distance between the nozzle and the gelling bath. The produced
      barium-alginate microbeads were characterized by excellent morphological
      characteristics as well as a very narrow size distribution. The
      microencapsulation procedure did not alter the morphology and viability of the
      encapsulated WJMSCs. In addition, the current paper reports the functional
      properties in terms of secretive profiles of both free and encapsulated WJMSCs.
      The analyzed factors were members of the family of interleukins, chemokines,
      growth factors, and soluble forms of adhesion molecules. These experiments showed
      that despite encapsulation, most of the proteins analyzed were secreted both by
      the free and encapsulated cells, even if in a different extent. In conclusion,
      the described encapsulation procedure represents a promising strategy to utilize
      WJMSCs for possible in vivo applications in tissue engineering and biomedicine.

PMID- 19402786
TI  - In vitro adipogenic differentiation of preadipocytes varies with differentiation
      stimulus, culture dimensionality, and scaffold composition.
AB  - Despite the rapidly growing body of work on stem cell-based adipose tissue
      engineering, there remains much to be learned about the role of the scaffold and
      culture environments in directing the adipogenic differentiation of cells. The
      present study examined how various culture environments and differentiation
      stimuli (traditional differentiation medium [DM] and coculture with mature
      adipocytes) impacted the adipogenic differentiation of human preadipocytes, with
      studies progressing from two-dimensions (2D) to three-dimensions (3D) in vitro.
      Assays for adipogenic markers (leptin, adiponectin, and glycerol) and Oil Red O
      staining were used to assess differentiation. After 16 days of 2D culture,
      adipogenesis was substantially greater when preadipocytes were cocultured with
      adipocytes rather than treated with DM. In a 3D in vitro environment, the
      production of adipogenic markers was significantly elevated relative to 2D
      conditions, and the coculture condition continued to stimulate greater
      adipogenesis. Alterations in 3D scaffold physical properties had only a minimal
      effect on the function of mature adipocytes, but significantly impacted the
      ability of preadipocytes to undergo adipogenic differentiation in vitro. These
      alterations in scaffold environment and in medium conditions, particularly the
      application of adipocyte/preadipocyte coculture methods in lieu of traditional
      DM, may provide further means for optimizing adipogenic outcomes in vitro and in
      vivo.

PMID- 19402782
TI  - Pain catastrophizing: a critical review.
AB  - Pain catastrophizing is conceptualized as a negative cognitive-affective response
      to anticipated or actual pain and has been associated with a number of important
      pain-related outcomes. In the present review, we first focus our efforts on the
      conceptualization of pain catastrophizing, highlighting its conceptual history
      and potential problem areas. We then focus our discussion on a number of
      theoretical mechanisms of action: appraisal theory, attention bias/information
      processing, communal coping, CNS pain processing mechanisms, psychophysiological
      pathways and neural pathways. We then offer evidence to suggest that pain
      catastrophizing represents an important process factor in pain treatment. We
      conclude by offering what we believe represents an integrated heuristic model for
      use by researchers over the next 5 years; a model we believe will advance the
      field most expediently.

PMID- 19402787
TI  - Effect of serum and growth factors on chondrogenic differentiation of synovium
      derived stromal cells.
AB  - We used fetal bovine serum (FBS) and different growth factors to investigate
      their potential for inducing chondrogenic differentiation of synovium-derived
      stromal cells. Human synovium was harvested from patients suffering from
      osteoarthritis and expanded in monolayer. To evaluate the effect of serum and
      growth factors on chondrogenic differentiation, 10 ng/mL of transforming growth
      factor-beta1 (TGF-beta1), 100 ng/mL of bone morphogenic protein-2 (BMP-2), 100
      ng/mL of insulin-like growth factor-1, 20 ng/mL of basic fibroblast growth factor
      (bFGF), and 10% FBS were added to the chemically defined chondrogenic medium
      singly or in combination during pellet culture for 21 days. The cell size and
      weight, glycosaminoglycan content, histology, and cartilage matrix-associated
      genes expression were analyzed. TGF-beta1 alone and TGF-beta1 + BMP-2 induced
      chondrogenic differentiation of synovium-derived stromal cells and synthesized
      cartilage-like matrix confirmed by histological analysis and
      immunohistochemistry. FBS, BMP-2, insulin-like growth factor-1, and bFGF as a
      single factor or other combinations except for TGF-beta1 + BMP-2 hardly induced
      chondrogenesis. Chondrogenic differentiation appeared to be inhibited when bFGF
      or the serum was added to the chondrogenic medium during pellet culture. The
      results of this study demonstrate the negative or positive role of serum and
      growth factors on chondrogenic differentiation of synovium-derived stromal cells.

PMID- 19402789
TI  - Cryptococcosis in solid-organ, hematopoietic stem cell, and tissue transplant
      recipients: evidence-based evolving trends.
AB  - The impact of current transplantation practices on the characteristics of
      cryptococcosis in solid-organ transplant recipients is not well defined. The
      incidence of cryptococcal disease among solid-organ transplant recipients has
      remained unchanged; however, patients are less likely to present with central
      nervous system or disseminated disease and are more likely to have cryptococcosis
      limited to the lungs. Additionally, lipid formulations of amphotericin B are now
      used more frequently, whereas their use in combination with flucytosine has
      decreased. The overall mortality of cryptococcosis has significantly improved in
      the current era. Renal failure remains associated with poor outcome, whereas use
      of lipid formulations of amphotericin B is associated with a higher survival
      rate. Despite rare infectious complication, certain peculiar attributes of
      cryptococcal disease in hematopoietic stem cell recipients and tissue transplant
      recipients warrant recognition.

PMID- 19402791
TI  - Proficiency testing project for brain natriuretic peptide (BNP) and the N
      terminal part of the propeptide of BNP (NT-proBNP) immunoassays: the
      CardioOrmocheck study.
AB  - BACKGROUND: We organized and conducted a proficiency testing study
      (CardioOrmocheck) to evaluate the differences in analytical performance of brain
      natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) immunoassays.
      METHODS: Approximately 90 Italian laboratories were involved in the 2005-2007
      proficiency testing cycles, while 112 laboratories took part in the 2008 cycle
      (from January to May 2008). A total of 28 study samples were measured by
      participating laboratories for a total of 2354 determinations. RESULTS: The mean
      total variability for BNP (50.6 %CV) was significantly higher than that for NT
      proBNP (8.4 %CV). In addition, the mean variability due to differences between
      methods (46.4 %CV) comprised the majority of the total variability for BNP.
      Between-method variability for BNP comprised, on average, 84% of total
      variability, while the within-method variability comprised an average of 20.2
      %CV. On the contrary, for NT-proBNP the within-method variability (7.3 %CV)
      represented the majority of total variability (average 75%), while between-method
      variability was smaller (4.1 %CV). Imprecision around the cut-off value showed
      marked differences among methods, especially for BNP immunoassay methods. In
      addition, BNP methods were affected by large systematic differences, for example
      an average 2.7-fold difference between Access and ADVIA Centaur methods, while
      agreement between NT-proBNP methods was better (an average 1.2-fold difference
      between Dimension and ECLIA on the Elecsys methods). CONCLUSIONS: This
      multicenter collaborative study demonstrates that there are significant
      differences in analytical characteristics and measured values among the most
      popular commercial methods for BNP and NT-proBNP. Clinicians should be very
      careful when comparing results obtained by laboratories that use different
      methods.

PMID- 19402790
TI  - A population-based study of infectious syphilis rediagnosis in British Columbia,
      1995-2005.
AB  - BACKGROUND: The Canadian province of British Columbia has experienced an ongoing
      heterosexual infectious syphilis epidemic since July 1997. In this study, we
      sought to characterize individuals who received a diagnosis of syphilis more than
      once in a cohort of reported cases from 1995 through 2005 in British Columbia.
      METHODS: Data for all cases of primary, secondary, and early latent syphilis from
      1 January 1995 through 31 December 2005 were extracted from the British Columbia
      Provincial Sexually Transmitted Disease Surveillance Database. A descriptive
      analysis was conducted on all variables from the cases, and the incidence density
      of syphilis rediagnosis was calculated. Bivariate and multivariate analyses were
      conducted using Cox proportional hazards regression techniques to compare those
      who received a syphilis diagnosis once with those who received a syphilis
      diagnosis more than once within the 10-year period. RESULTS: By 2006, up to 10%
      of new cases of syphilis in the province were attributed to individuals who had
      received a previous diagnosis of syphilis within the preceding 10 years. In Cox
      proportional hazards regression analysis, individuals with the following
      characteristics were associated with an increased risk of becoming reinfected
      with syphilis: human immunodeficiency virus seropositivity, history of ever
      having gonorrhea or chlamydia, aboriginal ethnicity, and being a man who had sex
      with men. CONCLUSIONS: In this study, an increasing proportion of syphilis cases
      in British Columbia were attributed to a rediagnosis during the previous decade.
      Individuals with syphilis rediagnosis may represent a core group of transmitters
      who continue to engage in risky behavior and sustain the epidemic. Policies for
      prevention need to better consider the role of interventions to decrease rates of
      repeat diagnoses of sexually transmitted infections.

PMID- 19402792
TI  - Increased CA 19-9 level in patients without malignant disease.
AB  - BACKGROUND: The measurement of carbohydrate antigen 19-9 (CA 19-9) is recommended
      for the diagnosis and follow-up of pancreatic cancer. However, increased CA 19-9
      has also been reported in patients with various benign diseases of the lung. We
      aimed to elucidate the pulmonary radiographic abnormalities and laboratory
      results associated with increased concentrations of CA 19-9. METHODS: This study
      was performed using a case-controlled design. Cases included all participants in
      a cancer screening program who had an increased CA 19-9 concentration (>37 U/mL),
      but without a diagnosis of malignancy. Age- and sex-matched participants with
      normal CA 19-9 levels were enrolled as controls. Laboratory results and
      radiographic features were compared. RESULTS: In total, 119 participants with
      increased CA 19-9 concentrations and 476 controls were included. A higher
      erythrocyte sedimentation rate (ESR) [adjusted odd ratio (aOR), 1.03; 95%
      confidence interval (CI), 1.01-1.05], higher hemoglobin A(1c) (HbA(1c)) (aOR,
      1.28; 95% CI, 1.05-1.56), bronchiectasis (aOR, 2.48; 95% CI, 1.22-5.02),
      bronchiolitis (aOR, 3.93; 95% CI, 1.88-8.22), emphysema (aOR, 2.67; 95% CI, 1.32
      5.40), and interstitial fibrosis (aOR, 10.62; 95% CI, 2.03-55.44) were
      independent factors for increased CA 19-9. CONCLUSIONS: CA 19-9 concentrations,
      as well as increased ESR and HbA(1c), can be increased in patients with various
      lung abnormalities.

PMID- 19402793
TI  - Detection of Hpdel in healthy individuals and cancer patients in Taiwan.
AB  - BACKGROUND: We investigated the genotypic distribution of Hp(del) in healthy
      subjects and cancer patients in Taiwan. METHODS: Blood samples were collected
      from 244 randomly selected healthy Taiwanese volunteers and 737 patients with
      various cancers. Samples were analyzed for the haptoglobin (Hp) gene, and the
      presence of the Hp(del) allele was determined from genomic DNA by an Hp(del)
      specific polymerase chain reaction (PCR) method. The plasma concentration of Hp
      was also determined. RESULTS: The frequency of the Hp(del) allele was calculated
      to be 0.029, and was not different between the healthy subjects and patients with
      cancer. The prevalence of Hp deficiency caused by Hp(del) homozygosity was
      estimated to be approximately 0.85 in 1000. Fifty-seven subjects were
      reclassified from homozygous Hp(1) or Hp(2) to Hp(1)/Hp(del) or Hp(2)/Hp(del)
      genotypes. The Hp(del) allele is not associated with prevalence, severity or
      stage of any cancer. CONCLUSIONS: Congenital Hp deficiency caused by Hp(del)
      homozygosity is a condition present in Taiwan with a relatively high frequency.
      However, the Hp(del) variant does not play a role in cancer.

PMID- 19402794
TI  - Quality-adjusted life-years as decisionmaker tools to address limitations
      inherent in number-needed-to-treat/harm values.

PMID- 19402795
TI  - Using statins to treat 'healthy' patients: are we there yet?

PMID- 19402796
TI  - Health economic evaluation: in need of more analytical rigor or more practical
      relevance?

PMID- 19402798
TI  - Pharmacoeconomic benefits of dasatinib in the treatment of imatinib-resistant
      patients with chronic myelogenous leukemia.
AB  - Treatment with imatinib has demonstrated high response rates and improved
      prognosis in chronic myelogenous leukemia. However, while the short-term response
      to imatinib is high, there are some concerns that the long-term response is
      substantially lower. Durable response with imatinib is difficult to achieve in
      patients with resistant disease. The use of higher doses has also been associated
      with increased toxicity and intolerance. Dasatinib is a new SRC-ABL-kinase
      inhibitor that has been developed for treating chronic myelogenous leukemia
      patients, across all phases of disease, who are resistant or intolerant to
      imatinib. This article details the existing evidence on the clinical efficacy,
      safety and value for money of dasatinib in the treatment of imatinib-resistant
      and -intolerant patients with chronic myelogenous leukemia. Dasatinib is
      associated with higher levels of response compared with high-dose imatinib. In
      addition, higher levels of response are associated with improved health outcomes
      in terms of both quality- and quantity-of-life years.

PMID- 19402800
TI  - Cost of treating otitis media in Australia.
AB  - OBJECTIVE: Otitis media (OM) is an inflammation of the middle ear. It is very
      common and associated with serious complications, including hearing loss. This
      study aimed to estimate the treatment costs of OM in Australia and the associated
      burden of disease (in disability-adjusted life-years). METHODS: Little Australia
      wide epidemiological information is available, so international studies in the
      main were used to estimate the incidence and prevalence by age and gender. These
      were triangulated against the available Australian data. Australian health data
      sets and data collected from the emergency department of a tertiary pediatric
      hospital were used to estimate the costs of primary care, pharmaceuticals,
      pathology and imaging, emergency department presentations, specialists, and
      admitted hospital care. RESULTS: Excluding the costs of the complications and
      comorbidities associated with OM, treatment costs for the disease in 2008 were
      between AUS$100 and 400 million. Visits to general practitioners and medicines
      constituted a high proportion of these costs. Antibiotic prescribing rates remain
      high despite clear evidence for a limited benefit from antibiotics for most OM
      cases and concerns regarding bacterial resistance. CONCLUSION: Treatment costs of
      OM in Australia are high and can only be estimated within a broad range. Further
      research on the links between antibiotics for OM and antibiotic resistance, and
      on the cost-effectiveness of prevention or amelioration of OM would be useful.

PMID- 19402799
TI  - In search of health: quality of life among postpartum Palestinian women.
AB  - OBJECTIVES: The postpartum period is a very important period for the health of
      the mother and the newborn. Despite its importance, research on this period is
      limited and tends to be more focused on biomedical aspects of the postpartum
      period. In the Occupied Palestinian Territory, little is known regarding women's
      postpartum wellbeing. This study utilizes the Maternal Postpartum Quality-of-Life
      instrument to assess Palestinian women's postpartum quality of life and the
      factors associated with variations in their quality-of-life scores. METHODS: A
      cross-sectional survey utilizing the adapted Maternal Postpartum Quality-of-Life
      Questionnaire was completed in the Occupied Palestinian Territory with a final
      sample size of 1020 women. RESULTS: The mean overall quality-of-life score for
      the sample was 21.53 (maximum = 30), suggesting that women are slightly satisfied
      with their lives in the postpartum period. Main variations in quality-of-life
      scores were associated with regional district, refugee status, the loss of a
      relative due to Israeli occupation violence, standard of living and pregnancy
      wantedness. CONCLUSION: The results of this study highlight the diversity and
      complexity of the social context, in particular the region where women live, and
      the issue of pregnancy wantedness in postpartum quality of life. They also call
      into question the services currently offered to postpartum women.

PMID- 19402801
TI  - Research and action: toward good quality of life and equity in health.
AB  - A brief summary of key presentations at the 15th Annual International Society for
      Quality of Life conference is presented. Special highlights of this conference
      were its location (South America) and its aim to present current and potential
      contributions of the health-related quality of life (QoL) field to equity in
      healthcare at a clinical and population level, providing crucial inputs for
      decision-making in a person-centered health conception. Present and future
      utilization of health-related QoL measures, norms and bank items were introduced
      by David Cella, who also called for researchers' cooperation, stating that
      efforts towards a commonly shared language and metric are better than a
      relentless pursuit of perfection. Other central topics in the search of equity
      were stigma and poverty. The importance of negative attributes by others in
      stigma severity perception and low self-reported QoL was demonstrated by Donald
      Patrick, who suggested interventions for reducing stigma. Poverty impact on
      children's QoL and the importance of social determinants were demonstrated
      through a unique, longitudinal Brazilian study. Complementarily, the importance
      of a biological basis of oncologic symptoms, particularly cytokines, and the
      impact of their control on health-related QoL were addressed by Charles Cleeland.
      The meeting stressed the combined importance of social, psychological and
      biological factors in determining patient-reported outcomes.

PMID- 19402802
TI  - Biosimilars and follow-on biologics.
AB  - This was the Center for Business Intelligence's 2nd Annual Summit on Biosimilars.
      The participants included industry, government, academics and private
      professionals involved in the myriad issues of biosimilars. Its purpose was to
      present a dialogue to evaluate the legal, regulatory and economic landscape in
      the USA and abroad and prepare for the anticipated US legislation that will
      enable the entry of biosimilars. Another conference will be held in September to
      discuss the various pending biosimilar bills in more detail or the new law, if
      passed.

PMID- 19402803
TI  - NICE at 10 years: new challenges ahead.
AB  - NICE has existed for 10 years. During this period, its methodological approach to
      developing guidance and assessing the value (cost-effectiveness) of healthcare
      interventions has received considerable national and international interest. At
      the same time, individual decisions have generated enormous controversy. This
      10th anniversary provides an opportunity to look back at how the institute has
      responded and adapted to the various challenges and controversies. Following Lord
      Darzi's review of the National Health Service (UK) in 2008, the institute took on
      further responsibilities for setting clinical standards for the National Health
      Service. This article explores these developments and speculates on future
      trends.

PMID- 19402804
TI  - Premenstrual syndrome and premenstrual dysphoric disorder: quality of life and
      burden of illness.
AB  - Premenstrual symptoms are distressing for up to 20% of reproductive-aged women
      and are associated with impairment in interpersonal or workplace functioning for
      at least 3-8%. Typical symptoms of premenstrual syndrome and the severe form,
      premenstrual dysphoric disorder, include irritability, anger, mood swings,
      depression, tension/anxiety, abdominal bloating, breast pain and fatigue. The
      symptoms recur monthly and last for an average of 6 days per month for the
      majority of the reproductive years. For women with premenstrual dysphoric
      disorder, the symptoms can be as disabling as major depressive disorder. It has
      been estimated that affected women experience almost 3000 days of severe symptoms
      during the reproductive years. Until two decades ago, there were no effective
      treatments for severe premenstrual syndrome. Even in 2000, almost three-quarters
      of women in the USA with premenstrual disorders either did not seek help or
      sought treatment unsuccessfully from at least three clinicians for over 5 years.
      This review will focus on the epidemiology, diagnosis, treatment outcomes,
      quality of life and burden of illness for premenstrual disorders.

PMID- 19402805
TI  - Optimizing the use of patient data to improve outcomes for patients: narcotics
      for chronic noncancer pain.
AB  - Randomized trials can provide important direction to clinical decision-making;
      however, their strength of inferences may be weakened by methodological
      limitations, the extent that their reported outcomes fail to address patient
      important end points and by failing to report results that provide interpretable
      estimates of magnitude of effect. Strategies that investigators can use to
      address interpretability include reporting mean differences between groups in
      relation to the minimal important difference and reporting the proportion of
      patients who benefit from treatment and the associated number needed to treat.
      These strategies also apply to reporting pooled estimates from meta-analyses,
      even when studies use different instruments to measure the same construct. We
      illustrate these techniques using, as an example, current evidence for the use of
      opioids in chronic noncancer pain.

PMID- 19402806
TI  - Applying Programme Budgeting Marginal Analysis in the health sector: 12 years of
      experience.
AB  - The Pharmaceutical Management Agency in New Zealand, PHARMAC, was established in
      1993 at a time when growth in pharmaceutical expenditure was very high and
      arguably unsustainable. PHARMAC was charged with finding new and effective ways
      to manage expenditure growth, while also obtaining the best health outcomes for
      the New Zealand population. In order to help achieve this goal, PHARMAC has used
      Programme Budgeting Marginal Analysis. The use of Programme Budgeting Marginal
      Analysis, together with a capped budget and tools to generate savings, has
      significantly contributed to PHARMAC achieving its objective. However, there are
      implications of using Programme Budgeting Marginal Analysis with a capped budget.
      In particular, a different approach is required when undertaking and using cost
      utility analysis (focused strongly on relative cost-effectiveness), and the
      opportunity cost of poor decisions is magnified significantly. As the demand on
      pharmaceutical expenditure continues to rise, the opportunity cost of not having
      a capped budget and tools for controlling pharmaceutical subsidies will only
      increase.

PMID- 19402808
TI  - Health promotion: essential to a national preventative health strategy.

PMID- 19402809
TI  - Demographic associations with stage of readiness to screen for colorectal cancer.
AB  - OBJECTIVE: To describe the distribution of a population in southern urban
      Adelaide in terms of readiness to screen for colorectal cancer (CRC) by Faecal
      Occult Blood Test (FOBT) or colonoscopy according to the stages in the
      Transtheoretical Model (TTM) of behaviour change and to compare the stages
      according to demographic variables. METHODS: A random sample of 664 South
      Australians aged 50 to 74 were surveyed in June 2006. Chi-squared analyses were
      performed to determine if statistically significant differences on demographic
      variables existed between participants at different stages of readiness to
      screen. RESULTS: The precontemplation and contemplation stages when combined
      equated to more than half of the total respondents. Several significant
      differences were identified between the stages. Those in both the
      precontemplation and contemplation stages were older than those in the remaining
      stages and also had a significantly higher proportion of women when compared to
      the action stage. In the precontemplation stage there were significantly more
      respondents for whom English was a second language, and low levels of private
      health insurance, whereas the contemplation stage had the highest proportion of
      Australian-born respondents. Interestingly, levels of private health insurance
      were also low among those who intended to screen with colonoscopy. CONCLUSIONS
      AND IMPLICATIONS: The majority of the population were not found to have
      progressed beyond contemplation. Certain demographic characteristics varied
      significantly between people at different stages of readiness to screen for CRC.

PMID- 19402810
TI  - Acculturation, sexual behaviour, risk and knowledge in Vietnamese men living in
      metropolitan Sydney.
AB  - OBJECTIVES: To describe the relationship between acculturation, sexual risk and
      sexually transmissible infections (STIs) and blood borne viruses (BBVs) knowledge
      among Vietnamese men living in inner Sydney and to compare this prevalence with
      national data. METHOD: Telephone interviews were completed with a random sample
      of Vietnamese men, selected from the electronic phone book using a list of common
      Vietnamese surnames. RESULTS: Of the 761 eligible men contacted, data were
      obtained from 499 men, giving a response rate of 66%. There was an association
      between lower acculturation scores and having more than 10 lifetime sexual
      partners, more than 50 lifetime sexual partners, never using a condom, ever or
      recently having commercial sex, ever having an STI, being hepatitis B carriers or
      ever being imprisoned. CONCLUSION: There is an association between acculturation
      and many aspects of sexual behaviour.

PMID- 19402811
TI  - Participation in physical activity: perceptions of women with a previous history
      of gestational diabetes mellitus.
AB  - ISSUE ADDRESSED: Women with a history of gestational diabetes mellitus (GDM) have
      an increased risk of developing type 2 diabetes mellitus (T2DM). Regular physical
      activity plays an important role in preventing T2DM. This study aimed to explore
      the perceptions of physical activity among women with previous GDM, in the
      context of preventing T2DM. METHODS: Individual semi-structured interviews were
      conducted with 10 women with previous GDM who had not been diagnosed with T2DM.
      Data were analysed using a modified grounded theory approach. RESULTS: Women
      perceived diet to be significantly more important for the prevention of T2DM than
      physical activity. They underestimated the role of physical activity in
      preventing diabetes, which may have resulted from the lack of information they
      received following their pregnancy. Women consistently placed the needs of their
      families before their own, despite acknowledging their future health risks. The
      most commonly cited constraints on physical activity participation were lack of
      time, partner support, and appropriate childcare. They identified a need for
      'family-friendly' community-based physical activity programs for mothers, more
      accessible childcare, and more information about the role of physical activity in
      diabetes prevention. CONCLUSIONS: Awareness of the role of physical activity for
      the prevention of diabetes was low. Physical activity promotion for women with
      previous GDM needs to be shaped around the opportunities and constraints
      identified by this population group.

PMID- 19402812
TI  - Patterns of physical violence in youth: the experience of 16 to 25 year olds.
AB  - ISSUE ADDRESSED: Physical violence among youth is an important public health
      issue. While data from hospital admissions and police reports can provide some
      information regarding the incidence of violence, little is known about violent
      incidents that are not reported to these agencies. This paper seeks to describe
      the self-reported experience and circumstances associated with the patterns of
      physical violence among 16-25 year olds. METHODS: Data from the 2004 New South
      Wales (NSW) Adult Health Survey were analysed regarding the selfreported
      experience of physical violence of 16-25 year olds over a 12-month period and the
      circumstances associated with their experience of violence. RESULTS: Around one
      in 10 young people reported that they had been physically assaulted within the
      previous 12 months. For males, their attacker was commonly previously unknown to
      them, intoxicated at the time of the incident, and the incident commonly occurred
      in an outdoor location or at a licensed premises. For females, their attacker was
      commonly a spouse or partner and the incident commonly occurred at home or in the
      workplace. Around three-quarters of respondents did not report the assault to
      police or other appropriate authorities, and around two-thirds did not receive
      any medical treatment for an injury sustained following the attack. CONCLUSION:
      Public health policies and strategies should reflect the need to tackle the issue
      of youth violence in NSW, including long-term policies aimed at addressing both
      the economic and social causes of youth violence.

PMID- 19402813
TI  - Soft landings: encouraging compliance with safety standards in Local Government
      Authority playgrounds.
AB  - ISSUES ADDRESSED: Consistent with health promotion principles of good practice,
      addressing playground injury necessitates the creation of a supportive
      environment for the enhancement of wellbeing and the prevention of injuries. This
      study aims to survey local governments to: determine compliance with playground
      safety standards; establish frequency of playground inspections and maintenance;
      and identify motivators and barriers to compliance with safety standards.
      METHODS: A survey of key informants for playground safety in all 152 local
      government councils in New South Wales (NSW) was undertaken. RESULTS: Of 152
      local councils in NSW (43 metropolitan and 109 non-metropolitan), 71.7% (n=109)
      completed the survey, 12.5% (n=19) refused to participate and no response was
      received by 15.8% (n=24). Self-reported compliance with key aspects of the
      standard was generally high. However, only 55% of councils complied with surface
      impact attenuation <200 gmax and <1,000 HIC. Further, only 14.7% of councils
      reported impact testing the playground surface during inspections. The main
      motivators to compliance included: reducing risk of litigation or liability;
      enhancing community and child safety, and minimising the risk of injury. The main
      barriers included a lack of: time; personnel, and a lack of adequate and
      appropriate funding. CONCLUSIONS: Local Government Authorities have a duty of
      care to ensure the safety of playgrounds in their jurisdiction. They require
      time, personnel and adequate and appropriate funding in order to achieve this
      aim.

PMID- 19402814
TI  - Hepatitis C education and support in Australian prisons: preliminary findings of
      a nationwide survey.
AB  - ISSUE ADDRESSED: Rates of hepatitis C infection are up to 60 times higher in
      correctional facilities than in the general population, yet prisoners have
      limited access to many methods of blood-borne virus prevention. The aim of this
      study was therefore to explore the efficiency of hepatitis C education and
      support services available in custodial settings, from the perspective of health
      educators and policy makers. METHODS: Semi-structured interviews were conducted
      with 23 health professionals, from all states and territories of Australia, who
      were involved in the management or provision of hepatitis C education or support
      to prisoners. Results were interpreted using thematic analysis. RESULTS:
      Participant reports regarding the provision of hepatitis C education and support
      services varied considerably between prisons and across states. Interviewees
      identified successful services and barriers to improvement, including limited
      time, insufficient funding and frequent personnel changes. Many prisons were
      believed to have unique needs and educators from external agencies were not
      always aware of the medical procedures or methods of harm reduction available in
      particular facilities. CONCLUSIONS: Interviewee perceptions indicated that the
      delivery of hepatitis C education and support services in Australian custodial
      settings is marred by inconsistency. However, both education programs and
      psychological support services could be developed by external agencies wishing to
      reduce the impact of hepatitis C within the prison system.

PMID- 19402815
TI  - Staying active, staying strong: pilot evaluation of a once-weekly, community
      based strength training program for older adults.
AB  - ISSUE ADDRESSED: Little is known about the effectiveness of once-weekly strength
      training programs for older adults based in community settings. This pilot study
      evaluated such a program to assess changes in the functional fitness of
      participants. METHODS: A pre-test/post-test within subjects study design was used
      with new participants in the 10-week Staying Active, Staying Strong (SASS)
      program (all aged 50+ years). The Seniors Fitness Test (SFT) and SF-36 were used
      to assess functional fitness and health-related quality of life respectively.
      Perception of physical ability was assessed using a study-specific questionnaire.
      Pre- and post-test SFT and SF-36 scores were compared using paired t-tests.
      Frequency of responses was used to describe participant perceptions. RESULTS: 110
      evaluation participants (mean age 68.2 years; 85% female), 49% of those who
      completed the pre-test, also completed the post-test. Evaluation participants
      significantly improved their strength (assessed using arm curls and sit-to
      stand); endurance (two-minute step test); flexibility (sit and reach, back
      scratch); and agility/dynamic balance (eight-foot up and go). SF-36 physical
      functioning domain scores also significantly improved. Most participants reported
      improved strength, fitness, mobility, general well-being and confidence in
      performing daily activities. CONCLUSION: Weekly, community-based strength
      training programs show promise in improving the functional capacity, including
      the strength, of older adults. More thorough evaluation is now required to
      confirm these findings.

PMID- 19402816
TI  - Computer-tailored weight reduction interventions targeting adults: a narrative
      systematic review.
AB  - ISSUE ADDRESSED: Potentially modifiable risk factors such as high body mass,
      physical inactivity and poor nutrition are, when combined, the largest
      contributors to the preventable burden of disease in Australia. Computer
      tailoring has shown promise in modifying lifestyle risk factors. This paper
      describes a narrative systematic review examining the evidence for 'second'
      generation computer-tailored primary prevention weight reduction interventions.
      METHOD: Studies published from January 1996-2008 were identified through
      electronic databases and searches of reference lists of relevant articles. Only
      randomised controlled trials or quasi-experimental designs with pretest and post
      test weight reduction outcome data were included. RESULTS: Six articles were
      identified, three of which reported significant positive effects. The
      intervention intensity and duration, method of tailoring and theory used
      differed. The internal validity was good but external validity poor for the
      majority of studies. CONCLUSIONS: The evidence of effectiveness for computer
      tailored primary prevention interventions for weight reduction is limited to a
      small number of heterogeneous studies. There is uncertainty whether reported
      effects are generalisable and sustained. The relative success of different
      components of efficacious interventions and the optimal intervention intensity
      and tailoring methods are unclear.

PMID- 19402817
TI  - Using paid mass media to teach the warning signs of stroke: the long and the
      short of it.
AB  - OBJECTIVE: Stroke is a major cause of morbidity and mortality and rapid treatment
      is critical to patient outcomes. This paper looks at the effect of paid
      television advertising campaigns upon the general public's knowledge of the
      warning signs of stroke and emergency department (ED) stroke presentations.
      METHODS: Data for the study includes results of nine random-digit dialing
      telephone surveys conducted among Ontario adults aged 45 and over. The mean
      number of ED presentations for all strokes and for transient ischemic attacks
      (TIA) were obtained from the Registry of the Canadian Stroke Network (RCSN).
      RESULTS: Polls indicated that long advertising campaigns were associated with
      significant increases in the public's knowledge of stroke warning signs, while
      shorter campaigns were associated with much smaller increases. Time (as
      represented by month) was the single most important factor determining the mean
      number of ED presentations for total stroke but was not for TIAs. Campaign status
      (on or off the air) had a strong and significant effect on ED presentations when
      the advertising campaigns were long; when the advertising campaigns were
      shortened, there was no campaign effect. CONCLUSIONS: Long, intermittent
      campaigns are effective in increasing the public's awareness of the warning signs
      of stroke and may have a significant effect on ED presentations for stroke and
      TIA. Public awareness of stroke warning signs declines during advertising black
      outs, so short campaigns are less effective.

PMID- 19402818
TI  - Suitability of a structured Fundamental Movement Skills program for long day care
      centres: a process evaluation.
AB  - ISSUE ADDRESSED: Early childhood presents an opportunity to encourage development
      of Fundamental Movement Skills (FMS). Implementation of a structured program in
      the Long Day Care (LDC) setting presents challenges. Implementation of a
      structured FMS program FunMoves was assessed in LDC in metropolitan New South
      Wales. METHODS: LDC staff attended a training session conducted by trained Health
      Promotion Officers (HPOs) and completed an evaluation. During implementation HPOs
      completed lesson observations. De-identified attendance data was collected and
      director and staff feedback on the program including barriers to implementation
      was obtained via questionnaire. Qualitative information relevant to process
      evaluation was obtained via open questions on questionnaires, and a de-brief
      diary recording feedback from directors and staff. RESULTS: Knowledge of FMS and
      FunMoves and staff confidence to deliver the program were high after training. On
      average, staff stated they ran lessons more than the suggested twice weekly and
      the majority of children attended 1-3 lessons per week. However, lesson delivery
      was not as designed, and staff found FunMoves disruptive and time consuming. Six
      directors and the majority of staff thought that FunMoves could be improved.
      CONCLUSION: Structured program delivery was hampered by contextual issues
      including significant staff turnover and program length and structure being at
      odds with the setting. Implementation could be enhanced by guidelines for more
      flexible delivery options including less structured approaches, shorter and
      simpler lessons, ongoing conversations with the early childhood sector, in-centre
      engagement of staff and post-training support.

PMID- 19402819
TI  - Impact of a five-day short course on integration of health promotion into
      practice in north Queensland.
AB  - ISSUE ADDRESSED: Workforce development is one element of health promotion
      capacity building. This paper describes the extent to which participants in a
      five-day short course in health promotion, delivered three times in north
      Queensland during 2007, reported greater adoption of health promotion within
      their work roles, and the factors that affected the level of adoption. METHODS:
      Out of 54 course attendees, 39 completed a post-course survey five to nine months
      after completing the course (72% response rate). Additionally, 11 course
      attendees participated in a focus group or phone interview to explore survey
      findings. RESULTS: The courses succeeded in providing knowledge, skills,
      confidence and enthusiasm to undertake health promotion work. Eighty per cent of
      participants stated they had incorporated health promotion into their work
      frequently or all of the time since undertaking the course. Lack of understanding
      of health promotion from co-workers and managers, lack of organisational support
      and commitment, lack of resources, competing clinical priorities, and lack of
      time were cited as the main barriers for undertaking health promotion.
      CONCLUSIONS: The course met participant training needs. However, similar training
      across all levels of staff including management may help to develop
      organisational capacity, thereby building a more knowledgeable workforce that is
      supported to undertake health promotion as a core part of an organisation's
      business.

PMID- 19402820
TI  - The global financial meltdown and the need for a political economy of health
      promotion.

PMID- 19402824
TI  - Are we 'normal'?

PMID- 19402821
TI  - Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR).
AB  - mTOR (mammalian target of rapamycin) stimulates cell growth by phosphorylating
      and promoting activation of AGC (protein kinase A/protein kinase G/protein kinase
      C) family kinases such as Akt (protein kinase B), S6K (p70 ribosomal S6 kinase)
      and SGK (serum and glucocorticoid protein kinase). mTORC1 (mTOR complex-1)
      phosphorylates the hydrophobic motif of S6K, whereas mTORC2 phosphorylates the
      hydrophobic motif of Akt and SGK. In the present paper we describe the small
      molecule Ku-0063794, which inhibits both mTORC1 and mTORC2 with an IC50 of
      approximately 10 nM, but does not suppress the activity of 76 other protein
      kinases or seven lipid kinases, including Class 1 PI3Ks (phosphoinositide 3
      kinases) at 1000-fold higher concentrations. Ku-0063794 is cell permeant,
      suppresses activation and hydrophobic motif phosphorylation of Akt, S6K and SGK,
      but not RSK (ribosomal S6 kinase), an AGC kinase not regulated by mTOR. Ku
      0063794 also inhibited phosphorylation of the T-loop Thr308 residue of Akt
      phosphorylated by PDK1 (3-phosphoinositide-dependent protein kinase-1). We
      interpret this as implying phosphorylation of Ser473 promotes phosphorylation of
      Thr308 and/or induces a conformational change that protects Thr308 from
      dephosphorylation. In contrast, Ku-0063794 does not affect Thr308 phosphorylation
      in fibroblasts lacking essential mTORC2 subunits, suggesting that signalling
      processes have adapted to enable Thr308 phosphorylation to occur in the absence
      of Ser473 phosphorylation. We found that Ku-0063794 induced a much greater
      dephosphorylation of the mTORC1 substrate 4E-BP1 (eukaryotic initiation factor 4E
      binding protein 1) than rapamycin, even in mTORC2-deficient cells, suggesting a
      form of mTOR distinct from mTORC1, or mTORC2 phosphorylates 4E-BP1. Ku-0063794
      also suppressed cell growth and induced a G1-cell-cycle arrest. Our results
      indicate that Ku-0063794 will be useful in delineating the physiological roles of
      mTOR and may have utility in treatment of cancers in which this pathway is
      inappropriately activated.

PMID- 19402827
TI  - Does a nerve-sparing technique for potency affect continence after open radical
      retropubic prostatectomy?

PMID- 19402829
TI  - Integration of ERG gene mapping and gene-expression profiling identifies distinct
      categories of human prostate cancer.

PMID- 19402830
TI  - Robotic-assisted partial nephrectomy.

PMID- 19402836
TI  - The efficacy and safety of tiotropium in Chinese patients with stable chronic
      obstructive pulmonary disease: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Tiotropium is the only long-acting inhaled
      anticholinergic bronchodilator currently available in China, but information
      about its clinical effect in this population is limited. This meta-analysis
      assessed the efficacy and safety of tiotropium in Chinese patients with stable
      COPD. METHODS: An electronic search of the literature was undertaken to identify
      randomized controlled trials (RCTs) of tiotropium in Chinese patients, which were
      then assessed for inclusion in a meta-analysis. The efficacy and safety of
      tiotropium was compared with placebo and ipratropium, using the outcomes of
      FEV(1), FEV(1)%, symptoms, frequency of exacerbations, adverse events and safety.
      RESULTS: Eleven RCTs recruiting 1006 patients were included in the meta-analysis.
      Compared with both placebo and ipratropium, tiotropium significantly improved
      FEV(1)[weighted mean difference (WMD) = 304 mL, 95% CI 271-337], FEV(1)% (WMD =
      8.35%, 95% CI 5.40-11.31) and symptoms [relative risk (RR) = 2.00, 95% CI 1.61
      2.49]. Tiotropium significantly reduced the risk of exacerbations (RR = 0.07, 95%
      CI 0.01-0.54) compared with placebo, and there was a non-significant reduction in
      the risk of exacerbations compared with ipratropium (RR = 0.70, 95% CI 0.13
      3.75). Tiotropium was well tolerated with a similar safety profile to placebo and
      ipratropium (RR = 1.16, 95% CI 0.76-1.77, P = 0.49). CONCLUSIONS: Tiotropium
      improved pulmonary function and symptoms, reduced exacerbations and was well
      tolerated and safe. On the basis of its efficacy and safety profile, tiotropium
      appears to be a reasonable first-line choice for the management of Chinese
      patients with stable COPD. Additional long-term RCTs are required to further
      evaluate the efficacy and safety of tiotropium.

PMID- 19402837
TI  - Selective gelfoam embolization of primary racemose haemangioma of the bronchial
      artery.
AB  - A 54-year-old male presented with haemoptysis. Bronchial arteriography revealed a
      bent, meandering and dilated bronchial artery with vascular hyperplasia in
      multiple locations. The patient was diagnosed as having primary racemose
      haemangioma of the bronchial artery. Using a microcatheter, TorconNB (5 Fr) and
      Progreat (2.7 Fr), selective gelfoam embolization of the descending branch of the
      right bronchial artery was performed using the double catheter method. This
      approach would allow effective treatment of the haemorrhage and avoid spinal cord
      injury.

PMID- 19402838
TI  - Sclerosing haemangioma with lymph node metastasis.
AB  - Sclerosing haemangioma (SH) of the lung is an intrapulmonary tumour composed of
      polygonal and cuboidal cells arranged in a heterogeneous pattern. SH is generally
      regarded as benign or very low-grade; only rarely have cases of lymph node
      metastasis been reported. We report a case of SH with metastasis to the regional
      lymph nodes in an 18-year-old male, whose left lung tumour was identified
      incidentally on routine CXR. The left upper lobe was removed and the regional
      lymph nodes dissected. The tumour consisted of proliferative cuboidal and
      polygonal cells arranged in a papillary pattern within the sclerotic stroma.
      Subcapsular metastasis was observed in a lymph node. SH with lymph node
      metastasis was diagnosed. The patient was disease-free at follow up after 2
      years. Lobectomy with nodal dissection is suggested for the treatment of
      pulmonary SH, especially in the case of large tumours with enlargement of
      regional lymph nodes. Investigation of more cases and long-term follow up are
      necessary to assess the clinical significance of lymph node metastasis.

PMID- 19402839
TI  - Therapeutic embolization of systemic arterial supply to normal basal segments of
      the left lower lobe of the lung.
AB  - Systemic arterialization of normal lung without sequestration is a rare
      congenital abnormality. The basal segments of the left lower lobe are most
      frequently involved. The involved lung has no structural abnormalities of the
      tracheobronchial tree that distinguish this abnormality from bronchopulmonary
      sequestration. Haemoptysis and exertional dyspnoea are common presenting
      symptoms. We report the case of a 26-year-old man who presented with recurrent
      haemoptysis due to systemic arterialization of basal segments of the left lower
      lobe of the lung, without sequestration. Therapeutic embolization using metallic
      coils was successfully performed without any complications. There was no further
      haemoptysis during a 6-month follow up. Therapeutic embolization is a safe and
      effective method of managing the haemoptysis associated with aberrant systemic
      arterial supply to the normal lung.

PMID- 19402840
TI  - Reasons for visiting Polish primary care practices by patients aged 18-44 years:
      the largest emigrating age group.
AB  - Over 3% of the entire Polish population migrate for a job within the European
      Union, most are aged 18-44 years. The main destinations are Germany, the United
      Kingdom and Ireland. Immigration is connected with the use of many public
      services, including healthcare services. Assuming Polish immigrants require
      medical consultations in the countries they reside in, the authors have analysed
      the reasons for patients' visits to general practitioners (GPs) in Poland in
      order to predict possible reasons why Polish patients living abroad may make
      appointments with GPs in other countries. Data from 22,769 visits to GP practices
      between June 2005 and May 2006 by Polish patients aged 18-44 years were collected
      electronically. Age was categorised into three groups (18-24, 25-4 and 35-44
      years) and the reason for the visit was categorised according to the ICD 10
      coding system. Among the 12,535 patients registered with GPs, 73.1% of women and
      68.6% of men required consultations during the year the study was conducted. The
      highest percentage of visits was recorded for women aged 35-44 years, while men
      of the same age were the least likely to visit a GP. The mean number of visits
      per patient ranged from 1.89 for men aged 25-34 years to 3.11 for women aged 35
      44 years. The means were similar for 18- to 24-year-old men and women. Women aged
      35-44 years had a higher mean number of visits compared with women aged 18-4
      years, whereas the opposite was true for men. The analysis of reasons for visits
      within the age groups indicated that the percentage of appointments for
      respiratory problems and general and unspecified problems dropped by more than
      half from the 18-24-year-olds to the 35-44-years-olds, while visits for
      musculosceletal, cardiovascular, and mental and behavioural problems increased by
      a factor of four. The presented results intend to enable healthcare services meet
      Polish immigrants' healthcare needs.

PMID- 19402847
TI  - A conceptual model of the experience of dyspnea and functional limitations in
      chronic obstructive pulmonary disease.
AB  - OBJECTIVES: Identify important patient-reported concepts of dyspnea and
      associated activities to develop a dyspnea-specific conceptual model for chronic
      obstructive pulmonary disease (COPD). METHODS: Using grounded theory
      methodologies, we identified key concepts through interviews with 25 COPD
      patients, review of scientific literature, and input from 22 experts. RESULTS:
      Constant comparative thematic analysis of data suggested five primary components
      of the dyspnea experience: breathlessness, fatigue, activity modification,
      activity limitation, and emotional response. Two major influences on dyspnea were
      described as individual exertion and exposure to environmental factors. Patients
      described a sense of dyspnea-related fear, and reported distress over the impact
      of dyspnea on health and activity limitation. They emphasized coping via
      behavioral strategies and medication, and reported that dyspnea caused the
      stopping or scaling back of activities, taking more time to do things and using
      adaptive measures or equipment. No existing model of dyspnea in COPD incorporated
      all of these concepts. We, therefore, developed a dyspnea-specific conceptual
      model in which the most proximal of concepts (dyspnea symptoms) can impair
      function and are mediated by personal and environmental factors. CONCLUSION:
      Patient and expert input guided the development of a comprehensive dyspnea
      specific conceptual model for COPD which will inform the design of future patient
      reported outcome measurement tools used to assess dyspnea and related functional
      limitations.

PMID- 19402848
TI  - Costs of medication nonadherence in patients with diabetes mellitus: a systematic
      review and critical analysis of the literature.
AB  - OBJECTIVES: Information on the health care costs associated with nonadherence to
      treatments for diabetes is both limited and inconsistent. We reviewed and
      critically appraised the literature to identify the main methodological issues
      that might explain differences among reports in the relationship of nonadherence
      and costs in patients with diabetes. METHODS: Two investigators reviewed Medline,
      EMBASE, Cochrane library and CINAHL and studies with information on costs by
      level of adherence in patients with diabetes published between January 1, 1997
      and September 30th 2007 were included. RESULTS: A total of 209 studies were
      identified and ten fulfilled the inclusion criteria. All included studies
      analyzed claims data and 70% were based on non-Medicaid and non-Medicare
      databases. Low medication possession ratios were associated with higher costs.
      Important differences were found in the ICD-9/ICD-9 CM codes used to identify
      patients and their diagnoses, data sources, analytic window period, definitions
      of adherence measures, skewness in cost data and associated statistical issues,
      adjustment of costs for inflation, adjustment for confounders, clinical outcomes
      and costs. CONCLUSIONS: Important variation among cost estimates was evident,
      even within studies of the same population. Readers should be cautious when
      comparing estimated coefficients from various studies because methodological
      issues might explain differences in the results of costs of nonadherence in
      diabetes. This is particularly important when estimates are used as inputs to
      pharmacoeconomic models.

PMID- 19402849
TI  - Is there anything nicer than NICE? A question the Conservative shadow health team
      is right to ask.
AB  - Access to life-saving treatments, and the role played by the National Institute
      for Health and Clinical Excellence (NICE) in reaching decisions, continues to
      represent an important part of modern health policy. High profile cases and
      critical media coverage have sharpened public interest in this issue. In November
      2008, the Conservative Party published detailed proposals on NICE outlining
      policies for improving the systems and processes for making decisions about NHS
      drug availability. The Conservatives clearly state their support for NICE, but
      highlight six areas to improve its configuration, structure and efficiency. These
      areas are consistent with the Conservative commitment to focus on health outcomes
      rather than central targets. A "NICE Charter" to codify the Institute's roles and
      responsibilities; scrapping the current system of Ministerial referral; allowing
      appraisals to commence at the time of drug licensing; and increasing the use of
      risk-sharing schemes are among the headline pledges. The policy document also
      makes clear the need for pharmaceutical companies to better demonstrate product
      clinical value by shifting the burden of proof from NICE to the manufacturer.
      Improved cooperation between industry and NICE is promised through the creation
      of a steering committee. Furthermore, a clear commitment to evaluate wider social
      costs and benefits is provided. The Conservative proposals make clear that there
      are no easy solutions to tackle the basic health economic problem of how to best
      allocate finite NHS resources to satisfy all healthcare needs. However, the
      proposals offer a solid blueprint for focused reform moving forward.

PMID- 19402850
TI  - A patient-based utility measure of health for clinical trials of cancer therapy
      based on the European Organization for the Research and Treatment of Cancer
      Quality of Life Questionnaire.
AB  - BACKGROUND: The European Organization for the Research and Treatment of Cancer
      Quality of Life Questionnaire (QLQ-C30) is a widely used quality-of-life measure
      in oncology. The ability to translate QLQ-C30 responses into utility scores would
      further expand its use in medical decision-making. The aims of this study were
      to: 1) map QLQ-C30 responses onto patient time trade-off utility scores; and 2)
      compare a multiattribute approach to a global evaluation approach to modeling
      utility scores. METHODS: Two distinct approaches were applied to data from 1432
      cancer patients. The multiattribute approach used psychometric analysis and
      expert input to select a subset of functioning and symptom scale items for
      modeling. The second approach focused on global health and quality-of-life items
      based on a conceptual model. Model selection criteria included parsimony,
      statistical significance and logical consistency of parameter estimates,
      predictive accuracy, number of states described, and scale range. RESULTS: The
      optimal multiattribute model included nine variables for five items from
      different scales, described 144 unique states, predicted values ranging from 0.63
      to 1.00, but it had poor predictive accuracy (cross-validation pseudo-R(2) =
      0.056). The best-fitting global approach-based model described 24 unique states
      using eight indicators for two items from one scale (plus a constant) and
      predicted values ranging from 0.17 to 1.00 (cross-validation pseudo-R(2) =
      0.127). CONCLUSIONS: Multiattribute models produced a greater number of unique
      predicted values, while global models exhibited more desirable statistical
      properties and a wider range of values. The recommended models will enable users
      to predict cancer patients' utilities from existing and future QLQ-C30 data sets.

PMID- 19402851
TI  - The effect of waiting time on health-related quality of life, pain, and physical
      function in patients awaiting primary total hip replacement: a randomized
      controlled trial.
AB  - OBJECTIVE: This prospective randomized study assessed the effect of waiting time
      (WT) on health outcomes in Finnish patients admitted to hospital for primary
      total hip replacement (THR). METHODS: A total of 395 consecutive patients with a
      need for a primary THR because of osteoarthritis and who were placed on the
      waiting list between August 2002 and November 2003. After placement on the
      waiting list, the patients were randomly assigned to a short WT (<or=3 months)
      group (n = 174) or a nonfixed WT group (n = 221). The patients completed self
      administered questionnaires at the time of placing on the waiting list and at
      hospital admission. Health-related quality of life was measured by the generic
      15D instrument. Hip pain and function were measured by the patient self-report
      Harris hip score (HHS). RESULTS: Of the 395 patients, 312 (79%) completed the
      follow-up (140 patients with short and 172 with nonfixed WT). At admission, the
      mean 15D scores for patients with short and nonfixed WT were 0.784 and 0.783,
      respectively. In the intention-to-treatment analysis, the difference between the
      groups (Delta 0.001, 95% confidence interval [CI]: -0.019 to 0.021) was not
      statistically significant or clinically important. The mean self-report HHS in
      patients with short WT was 43.5, and among those with nonfixed WT was 41.9. The
      difference (Delta 1.6, 95% CI: -1.77 to 4.87) was not statistically significant.
      CONCLUSIONS: Both generic and disease-specific measures revealed that longer WTs
      did not result in poorer health status at admission.

PMID- 19402852
TI  - Prospective validation of eight different adherence measures for use with
      administrative claims data among patients with schizophrenia.
AB  - OBJECTIVE: The aim of this study was to compare the predictive validity of eight
      different adherence measures by studying the variability explained between each
      measure and hospitalization episodes among Medicaid-eligible persons diagnosed
      with schizophrenia on antipsychotic monotherapy. METHODS: This study was a
      retrospective analysis of the Arkansas Medicaid administrative claims data.
      Continuously eligible adult schizophrenia (ICD-9-CM = 295.**) patients on
      antipsychotic monotherapy were identified in the recruitment period from July
      2000 through April 2004. Adherence rates to antipsychotic therapy in year 1 were
      calculated using eight different measures identified from the literature.
      Univariate and multivariable logistic regression models were used to
      prospectively predict all-cause and mental health-related hospitalizations in the
      follow-up year. RESULTS: Adherence rates were computed for 3395 schizophrenic
      patients with a mean age of 42.9 years, of which 52.5% (n = 1782) were females,
      and 52.8% (n = 1793) were white. The proportion of days covered (PDC) and
      continuous measure of medication gaps measures of adherence had equal C
      statistics of 0.571 in predicting both all-cause and mental health-related
      hospitalizations. The medication possession ratio (MPR) continuous multiple
      interval measure of oversupply were the second best measures with equal C
      statistics of 0.568 and 0.567 for any-cause and mental health-related
      hospitalizations. The multivariate adjusted models had higher C-statistics but
      provided the same rank order results. CONCLUSIONS: MPR and PDC were among the
      best predictors of any-cause and mental health-related hospitalization, and are
      recommended as the preferred adherence measures when a single measure is sought
      for use with administrative claims data for patients not on polypharmacy.

PMID- 19402854
TI  - No study left behind: a network meta-analysis in non-small-cell lung cancer
      demonstrating the importance of considering all relevant data.
AB  - OBJECTIVE: To demonstrate the importance of considering all relevant indirect
      data in a network meta-analysis of treatments for non-small-cell lung cancer
      (NSCLC). METHODS: A recent National Institute for Health and Clinical Excellence
      appraisal focussed on the indirect comparison of docetaxel with erlotinib in
      second-line treatment of NSCLC based on trials including a common comparator. We
      compared the results of this analysis to a network meta-analysis including other
      trials that formed a network of evidence. We also examined the importance of
      allowing for the correlations between the estimated treatment effects that can
      arise when analysing such networks. RESULTS: The analysis of the restricted
      network including only trials of docetaxel and erlotinib linked via the common
      placebo comparator produced an estimated mean hazard ratio (HR) for erlotinib
      compared with docetaxel of 1.55 (95% confidence interval [CI] 0.72-2.97). In
      contrast, the network meta-analysis produced an estimated HR for erlotinib
      compared with docetaxel of 0.83 (95% CI 0.65-1.06). Analyzing the wider network
      improved the precision of estimated treatment effects, altered their rankings and
      also allowed further treatments to be compared. Some of the estimated treatment
      effects from the wider network were highly correlated. CONCLUSIONS: This
      empirical example shows the importance of considering all potentially relevant
      data when comparing treatments. Care should therefore be taken to consider all
      relevant information, including correlations induced by the network of trial
      data, when comparing treatments.

PMID- 19402853
TI  - Construct validity of the Work Productivity and Activity Impairment questionnaire
      across informal caregivers of chronically ill older patients.
AB  - OBJECTIVES: To assess the validity of the Work Productivity and Activity
      Impairment questionnaire as adapted for caregiving (WPAI:CG) to measure
      productivity loss (hours missed from work, impairment while at work, and
      impairment in regular activities) due to unpaid caregiving for medically complex
      older adults. METHODS: The WPAI:CG was administered along with the Caregiver
      Strain Index (CSI) and Center for Epidemiologic Studies Depression Scale (CESD)
      to a caregiving population (N = 308) enrolled with their older, medically complex
      care-recipient in a cluster-randomized controlled study. Correlation coefficients
      were calculated between each productivity variable derived from the WPAI:CG and
      CSI/CESD scores. Nonparametric tests for trend across ordered groups were carried
      out to examine the relationship between each productivity variable and the
      intensity of the caregiving. RESULTS: Significant positive correlations were
      found between work productivity loss and caregiving-related strain (r = 0.45) and
      depression (r = 0.30). Measures of productivity loss were also highly associated
      with caregiving intensity (P < 0.05) and care-recipient medical care use (P <
      0.05). The average employed caregiver reported 1.5 hours absence from work in the
      previous week and 18.5% reduced productivity while at work due to caregiving.
      Employed and nonemployed caregivers reported 27.2% reduced productivity in
      regular activities in the previous week. CONCLUSION: The results indicate high
      convergent validity of the WPAI:CG questionnaire. This measure could facilitate
      research on the cost-effectiveness of caregiver-workplace interventions and
      provide employers and policy experts with a more accurate and comprehensive
      estimate of caregiving-related costs incurred by employers and society.

PMID- 19402855
TI  - Can NICE be nicer? In a world of budget constraints there are no easy solutions.
AB  - A recent article comments on some of the shortcomings of the National Institute
      for Health and Clinical Excellence (NICE) in the United Kingdom. This
      counterpoint article discusses the key issues in more detail and suggests ways in
      which NICE might improve, given the difficulties in making resource allocation
      decisions under a budget constraint.

PMID- 19402857
TI  - Red cell transfusion in elective cardiac surgery patients.

PMID- 19402856
TI  - International collaborative study to evaluate candidate reference reagents to
      standardize haemagglutination testing for anti-A and anti-B in normal intravenous
      immunoglobulin products.
AB  - BACKGROUND AND OBJECTIVES: The aim of the study was to evaluate, in an
      international collaboration, three lyophilized intravenous immunoglobulin (IVIG)
      preparations for their suitability to standardize and control haemagglutination
      testing for anti-A and anti-B in IVIG products. MATERIALS AND METHODS: Twenty
      three laboratories tested candidate IVIG reference reagents consisting of a
      Positive control (07/306), a Negative control (07/308), and a specifically
      formulated Limit preparation (07/310) to define the maximum (e.g. pharmacopoeial)
      limits of anti-A and anti-B in IVIG products, where limits are applicable.
      Laboratories performed direct haemagglutination using papain-treated erythrocytes
      and/or indirect antiglobulin tests. RESULTS: For both methods, there was up to 16
      fold variation in anti-A and anti-B titres, although there was good agreement
      over a two-fold titre range for anti-A and anti-B between laboratories for both
      07/306 and 07/310 using the direct method. Comparative titration data for 07/306
      and 07/310 indicated that the use of a 'Limit' reference reagent would facilitate
      identification of higher titre batches when the direct haemagglutination method
      is used. CONCLUSIONS: The establishment of preparations 07/306, 07/308 and 07/310
      as reference reagents by the World Health Organization will facilitate global
      standardization of haemagglutination tests for anti-A and anti-B, ensure that
      such tests are sufficiently sensitive and specific, and facilitate identification
      of batches that exceed maximum recommended levels of anti-A and anti-B. The
      Commission of the European Pharmacopoeia and the United States Food and Drug
      Administration have adopted the same reference reagents including the maximal
      specifications defined by preparation 07/310.

PMID- 19402858
TI  - Dopamine agonists, Dopplers and doubt: cabergoline-associated cardiac
      valvulopathy.

PMID- 19402859
TI  - Revaccination of bone marrow transplant recipients: a review of current practices
      in Australia.
AB  - BACKGROUND: Vaccination following bone marrow transplant (BMT) is an important
      part of ongoing care and disease prevention. The aim of the study was to
      investigate vaccination procedures in BMT recipients and identify what systems
      are in place throughout Australia to remind and alert patients concerning their
      need for vaccination. METHODS: Questionnaires were sent to haematologists
      managing BMT recipients in Australia to examine post-BMT vaccination practices in
      hospitals and outpatient clinics. Questionnaires were also sent to BMT recipients
      in New South Wales, who had their transplants (either allogeneic or autologous)
      in the past 5 years to determine what vaccinations they had received and what
      vaccination reminder systems had been used. RESULTS: Vaccine recommendations and
      practices by BMT physicians showed little consensus. They also differed greatly
      between autologous and allogeneic transplant recipients. Only just more than half
      of the physicians had an effective reminder system in place and only 12 of 34
      patients had received vaccination reminders. One-third of all patients were not
      aware of any need for revaccination. CONCLUSION: The disparity in physician
      practice regarding revaccination is significant and may reflect the lack of data
      available regarding efficacy of revaccination in this setting and/or a lack of
      knowledge about recommendations. Because of this, a national immunization
      schedule for post-BMT patients founded on evidence-based studies is required to
      provide optimal patient care. The lack of effective follow up and reminder
      systems ensuring patient completion of vaccination schedules is also an area
      needing improvement.

PMID- 19402860
TI  - They just don't get enough! Variable intern experience in bedside procedural
      skills.
AB  - BACKGROUND: Medical school and resident training programmes offer different
      learning opportunities and outcomes. The aim of the study was to assess medical
      student and intern experience in common clinical procedures. METHODS: Interns
      employed in a metropolitan teaching hospital from 2000 to 2004 completed a survey
      of experience and confidence in clinical procedures at the beginning and end of
      their intern year. Attendance at and the contribution to procedural confidence of
      a voluntary procedural skill-training programme were examined. RESULTS: For the
      314 interns, clinical experience before and during internship varied for each
      procedure and between year cohorts as did training programme attendance (44-84%).
      Student procedural confidence was predicted by pre-intern experience either on
      patients or by simulation (beta = 0.17, 95% confidence interval (CI) 0.02-0.21, P
      = 0.03) and age >30 years on commencing internship (beta = 8.44, 95%CI 3.03
      14.06, P = 0.003. Adjusted R(2) = 0.08, P = 0.002). Intern procedural confidence
      by year's end was predicted by attendance at the training programme (beta = 0.48,
      95%CI 0.34-0.62, P < 0.001), intern experience with patient procedures (beta =
      0.34, 95%CI 0.21-0.47, P < 0.001) and a clear decision to enter a postgraduate
      training programme (beta = 0.13, 95%CI 0.04-0.22, P = 0.007, Adjusted R(2) =
      0.50, P < 0.001). CONCLUSION: Interns and students receive variable experience to
      carry out procedural skills on patients. This makes designing training programmes
      difficult as training needs vary each year. Both mandatory supervision of key
      skills and opportunities to supplement limited experience are needed during the
      intern year to ensure a uniform experience.

PMID- 19402861
TI  - Methotrexate: long-term safety and efficacy in an Australian consultant
      rheumatology practice.
AB  - BACKGROUND: The aim of this study was to evaluate the rate and cause of
      methotrexate (MTX) termination in clinical practice, describe the types of
      toxicities noted, assess the incidence of achieving remission in rheumatoid
      arthritis (RA) patients and review the appropriateness of current clinical
      guidelines for monitoring MTX treatment. METHODS: A retrospective, case review of
      patients seen in a private rheumatology practice attached to a major Sydney
      Teaching Hospital was undertaken over an 18-year period. The primary outcome was
      time to cessation of MTX. RESULTS: Seven hundred and ninety patients satisfied
      the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity
      related discontinuation occurred in 93 patients (11.8%) and due to non-adverse
      reactions in 179 patients. The median duration of therapy in these two groups was
      2.0 and 2.9 years, respectively. There was no difference in the average maximum
      weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow
      up. Cox proportional hazards analyses showed that those of the female sex
      remained on treatment significantly longer than the male sex (hazard ratio (HR)
      0.73, 95% confidence interval (CI) 0.57-0.96; P = 0.014); patients with RA
      remained on treatment significantly longer than patients with seronegative
      arthritis (HR 0.56, 95%CI 0.42-0.74; P < 0.001). Being of the male sex aged more
      than 60 years and having a non-RA diagnosis predisposed to stopping MTX earlier.
      CONCLUSION: MTX is a safe and effective medication. Notable remission rates are
      achievable in patients with RA with current conventional treatment protocols. MTX
      has a low toxicity profile and this study stresses the need to re-evaluate and
      revise the current monitoring guidelines.

PMID- 19402862
TI  - Medical malpractice experience of Taiwan: 2005 versus 1991.
AB  - BACKGROUND: Medical malpractice litigation has become an important issue
      worldwide. Although many epidemiological studies have been carried out, most
      studies were conducted cross-sectionally in developed countries and focused on
      malpractice litigation. We conducted nationwide surveys to investigate
      physicians' experiences associated with malpractice in 1991 and 2005,
      respectively. METHODS: By stratified systemic sampling, questionnaires were
      mailed to physicians in 1991 and 2005. Physicians were asked about the experience
      of medical malpractice and outcomes of malpractice. The outcomes of the
      malpractice were classified as resolution, settlement and lawsuit. We also
      collected physicians' demographic and professional characteristics. RESULTS: The
      prevalence of malpractice experience decreased from 44.1% in 1991 to 36.0% in
      2005 (P = 0.004). The estimated annual malpractice claims decreased from 0.14 to
      0.10 per physician in 1991 and 2005, respectively (P < 0.001). Physicians 45-64
      years of age, obstetrician/gynaecologists and surgeons had significantly higher
      risk of malpractice. Compared with 1991, malpractice claims in 2005 were more
      likely to be brought into courts (23.1% in 2005 vs 15.7% in 1991, odds ratio (OR)
      = 1.48, P = 0.020). In litigation cases, malpractice events in 2005 had more than
      triple the risk of 1991 to be sued in both civil and criminal courts (12.4% in
      2005 vs 4.1% in 1991, OR = 3.31, P < 0.001). CONCLUSION: Compared with 1991,
      medical malpractice experiences were decreasing in prevalence, but increasing in
      severity in 2005. Additional studies, especially among different legal systems,
      are necessary to confirm these observations.

PMID- 19402863
TI  - Baseline and salt-stimulated paraoxonase and arylesterase activities in patients
      with chronic liver disease: relation to disease severity.
AB  - BACKGROUND: It has been recently reported that serum paraoxonase (PON1) and
      arylesterase (ARE) activities may be significantly reduced in patients with
      chronic liver disease. The aim of the study was to investigate the relations
      between serum PON1 and ARE activities and the degree of liver damage in patients
      with chronic liver injury. METHODS: We studied a total of 75 patients with
      chronic liver disease (50 patients with cirrhosis and 25 patients with chronic
      hepatitis) and 25 healthy comparison subjects. Baseline and salt-stimulated PON1
      and ARE activities were determined in all study participants. RESULTS: Baseline
      and stimulated PON1 and ARE activities were significantly lower in patients with
      chronic liver disease than in controls. Cirrhotic patients in Child-Pugh classes
      B and C subgroups had significantly reduced PON1 and ARE activities compared with
      Child-Pugh class A patients (both P-values <0.01). Receiver operating
      characteristic curve analysis showed that serum ARE activity was the most
      efficient test for identifying the presence and severity of chronic liver injury.
      CONCLUSION: Baseline and stimulated PON1 and ARE activities are reduced in
      patients with chronic liver disease. Serum ARE activity could be a suitable
      biomarker for the evaluation of the presence and severity of chronic liver
      damage.

PMID- 19402864
TI  - DNAzymes and their therapeutic possibilities.
AB  - Our increasing understanding of the regulatory mechanisms involved in the
      pathogenesis of disease is opening up opportunities for therapeutic intervention.
      To tackle the unmet disease burden, the last decade has seen the emergence of
      gene-targeting small-molecule nucleic acid-based strategies, such as antisense
      oligodeoxynucleotides, ribozymes, small interfering RNA and DNAzymes. DNAzymes
      represent promising candidates for drug therapy in a wide range of diseases, such
      as cancer and cardiovascular disorders. This brief review will discuss recent
      developments in DNAzymes and their therapeutic potential.

PMID- 19402865
TI  - Delayed adverse reactions to total-dose intravenous iron polymaltose.
AB  - The rate of infusion reactions to total-dose intravenous iron polymaltose is very
      low, but the frequency and severity of adverse reactions following the infusion
      are unknown. In 50 consecutive patients, adverse reactions developed up to 2 days
      after the infusion in 26% and lasted 1-8 days (median 4). Severe systemic
      reactions occurred in 8%. Patients should be warned of the chance of delayed
      reactions and an alternative iron preparation should be considered if parenteral
      iron is again indicated.

PMID- 19402866
TI  - Body mass index determines sunbathing habits: implications on vitamin D levels.
AB  - Vitamin D is crucial for calcium and bone metabolism. Overweight people have been
      found to have lower levels of this vitamin. The aim of the paper was to test if
      sun exposure habits might differ according to weight and body fat per cent in a
      random population-based sample, and have an impact on vitamin D levels. The
      analysis of 367 persons showed that, among other established factors, differences
      in sunbathing also explain the lower vitamin D levels in overweight and elderly
      individuals.

PMID- 19402867
TI  - Are guidelines on use of colony-stimulating factors in solid cancers flawed?
AB  - In cancer care in Australia, we are very reliant on an array of expensive
      pharmaceuticals. Our use of these treatments is often based on multinational or
      foreign clinical studies. Oncologists are, to varying degrees, reliant on how the
      studies are interpreted by the writers of journal editorials, clinical guidelines
      and opinion pieces. Therefore it is important that these guidelines are balanced
      and evidence based. We have examined in detail one of the most influential and
      wide ranging clinical guidelines used in oncology, The American Society of
      Clinical Oncology (ASCO) 2006 Update of Recommendations for the use of White
      Blood Cell Factors: An Evidence-Based Clinical Practice Guideline. We have
      discussed in detail some of the controversial recommendations in this guideline
      and have exposed what we believe are some flaws in these recommendations. We
      would urge that we continue to be rigorous in our oversight of international
      research agendas and international clinical guidelines in the future.

PMID- 19402868
TI  - Low-dose cabergoline causing valvular heart disease in a patient treated for
      prolactinoma.

PMID- 19402869
TI  - [18F]FDG PET/CT in the diagnosis of large vessel vasculitis.

PMID- 19402870
TI  - A challenge to the claims that fludarabine and cyclophosphamide is the new
      standard treatment for chronic lymphocytic leukaemia.

PMID- 19402873
TI  - Depolarization-activated calcium channels shape the calcium signatures induced by
      low-temperature stress.

PMID- 19402871
TI  - Selecting students for medical school: an evidenced-based approach.

PMID- 19402874
TI  - Arsenite efflux is not enhanced in the arsenate-tolerant phenotype of Holcus
      lanatus.
AB  - Arsenate tolerance in Holcus lanatus is achieved mainly through suppressed
      arsenate uptake. We recently showed that plant roots can rapidly efflux arsenite
      to the external medium. Here, we tested whether arsenite efflux is a component of
      the adaptive arsenate tolerance in H. lanatus. Tolerant and nontolerant
      phenotypes were exposed to different arsenate concentrations with or without
      phosphate for 24 h, and arsenic (As) speciation was determined in nutrient
      solutions, roots and xylem sap. At the same arsenate exposure concentration, the
      nontolerant phenotype took up more arsenate and effluxed more arsenite than the
      tolerant phenotype. However, arsenite efflux was proportional to arsenate uptake
      and was not enhanced in the tolerant phenotype. Within 2-24 h, most (80-100%) of
      the arsenate taken up was effluxed to the medium as arsenite. About 86-95% of the
      As in the roots and majority of the As in xylem sap (c. 66%) was present as
      arsenite, and there were no significant differences between phenotypes. Arsenite
      efflux is not adaptively enhanced in the tolerant phenotype H. lanatus, but it
      could be a basal tolerance mechanism to greatly decrease cellular As burden in
      both phenotypes. Tolerant and nontolerant phenotypes had a similar capacity to
      reduce arsenate in roots.

PMID- 19402875
TI  - Multiple layers of incompatibility to the parasitic witchweed, Striga
      hermonthica.
AB  - * Witchweeds (Striga spp.) are major agricultural pests that infest important
      crops in sub-Saharan Africa. Striga hermonthica parasitizes gramineous plants
      including sorghum, maize and rice, but not dicots. To understand host recognition
      mechanisms of S. hermonthica, we investigated its interaction with nonhost dicots
      including Arabidopsis, cowpea, Lotus japonicus and Phtheirospermum japonicum, a
      hemiparasite. * Striga hermonthica seeds were pretreated with strigol, a
      germination stimulant, and allowed to germinate next to a potential host root. We
      characterized the histological phenotype of the interactions. Moreover, we
      monitored the infection of a host rice and the nonhost P. japonicum by S.
      hermonthica using time-lapse photography. * All nonhost dicots tested did not
      support S. hermonthica shoot growth beyond the six leaf-pair stage; however, the
      arrest of parasite development occurred at different stages. Striga hermonthica
      haustoria were able to reach the steles of Arabidopsis and cowpea, while L.
      japonicus blocked S. hermonthica infection in the root cortex. Striga hermonthica
      often failed to penetrate P. japonicum roots. * Our analysis indicates that there
      are at least four types of incompatible interaction to S. hermonthica.
      Combinations of these different incompatibility mechanisms contribute to the
      total resistance to S. hermonthica.

PMID- 19402876
TI  - UVR8 in Arabidopsis thaliana regulates multiple aspects of cellular
      differentiation during leaf development in response to ultraviolet B radiation.
AB  - Responses specific to ultraviolet B (UV-B) wavelengths are still poorly
      understood, both in terms of initial signalling and effects on morphogenesis.
      Arabidopsis thaliana UV RESISTANCE LOCUS8 (UVR8) is the only known UV-B specific
      signalling component, but the role of UVR8 in leaf morphogenesis is unknown. The
      regulatory effects of UVR8 on leaf morphogenesis at a range of supplementary UV-B
      doses were characterized, revealing both UVR8-dependent and independent responses
      to UV irradiation. Inhibition of epidermal cell division in response to UV-B is
      largely independent of UVR8. However, overall leaf growth under UV-B irradiation
      in wild-type plants is enhanced compared with a uvr8 mutant because of a UVR8
      dependent compensatory increase of cell area in wild-type plants. UVR8 was also
      required for the regulation of endopolyploidy in response to UV-B, and the uvr8
      mutant also has a lower density of stomata than the wild type in the presence of
      UV-B, indicating that UVR8 has a regulatory role in other developmental events.
      Our findings show that, in addition to regulating UV-protective gene expression
      responses, UVR8 is involved in controlling aspects of leaf growth and
      morphogenesis. This work extends our understanding of how UV-B response is
      orchestrated at the whole-plant level.

PMID- 19402877
TI  - The chlorophyll-containing orchid Corallorhiza trifida derives little carbon
      through photosynthesis.
AB  - While measurements of tissue stable isotope signatures and isotope mixing models
      have suggested that the green orchid Corallorhiza trifida is photosynthetically
      active and hence only partially mycoheterotrophic, these assumptions have not
      been validated by direct analysis of carbon assimilation. The photosynthetic
      capabilities of three orchid species assumed on the basis of the indirect methods
      or chlorophyll content to have differing trophic strategies: Neottia nidus-avis
      (fully mycoheterotrophic), Cephalanthera damasonium (partially autotrophic), C.
      trifida (partially autotrophic), as well as saplings of an autotrophic tree,
      Fagus sylvatica, were investigated by combining the determination of chlorophyll
      content and fluorescence, with direct measurement of the potential for CO(2)
      assimilation using (13)C isotope tracers in the field. Chlorophyll content and
      fluorescence values were indicative of ineffective photochemical processes in
      Neottia and reduced efficiency of photochemical processes in Corallorhiza. These
      differences are reflected in the mean assimilation rates of (13)CO(2) of 594 +/-
      129, 331 +/- 72, 12.4 +/- 2.4 and 7.3 +/- 0.9 microg g(-1) h(-1) for Fagus,
      Cephalanthera, Corallorhiza and Neottia, respectively. Our study, while
      confirming the fully mycoheterotrophic status of Neottia and the partially
      autotrophic condition in Cephalanthera, also demonstrates under field conditions
      that Corallorhiza is physiologically closer to the fully mycoheterotrophic
      condition than has previously been recognized.

PMID- 19402878
TI  - Differing requirements for flavonoids during the formation of lateral roots,
      nodules and root knot nematode galls in Medicago truncatula.
AB  - * In this study, we tested whether the organogenesis of symbiotic root nodules,
      lateral roots and root galls induced by parasitic root knot nematodes
      (Meloidogyne javanica) was regulated by the presence of flavonoids in the roots
      of Medicago truncatula. Flavonoids accumulate in all three types of root organ,
      and have been hypothesized previously to be required for secondary root
      organogenesis because of their potential role as auxin transport regulators. *
      Using RNA interference to silence the flavonoid biosynthetic pathway in M.
      truncatula, we generated transformed flavonoid-deficient hairy roots which were
      used to study flavonoid accumulation, cell division and organogenesis of nodules,
      lateral roots and root galls. * Flavonoid-deficient roots did not form nodules,
      as demonstrated previously, but showed altered root growth in response to
      rhizobia. By contrast, flavonoid-deficient roots showed no difference in the
      number of lateral roots and root galls. Galls on flavonoid-deficient roots formed
      normal giant cells, but were shorter, and were characterized by reduced numbers
      of dividing pericycle cells. * We rejected the hypothesis that flavonoids are
      required as general regulators of the organogenesis of secondary root organs, but
      flavonoids appear to be necessary for nodulation. Possible reasons for this
      difference in the requirement for flavonoids are discussed.

PMID- 19402879
TI  - GhZFP1, a novel CCCH-type zinc finger protein from cotton, enhances salt stress
      tolerance and fungal disease resistance in transgenic tobacco by interacting with
      GZIRD21A and GZIPR5.
AB  - * Zinc finger proteins are a superfamily involved in many aspects of plant growth
      and development. However, CCCH-type zinc finger proteins involved in plant stress
      tolerance are poorly understood. * A cDNA clone designated Gossypium hirsutum
      zinc finger protein 1 (GhZFP1), which encodes a novel CCCH-type zinc finger
      protein, was isolated from a salt-induced cotton (G. hirsutum) cDNA library using
      differential hybridization screening and further studied in transgenic tobacco
      Nicotiana tabacum cv. NC89. Using yeast two-hybrid screening (Y2H), proteins
      GZIRD21A (GhZFP1 interacting and responsive to dehydration protein 21A) and
      GZIPR5 (GhZFP1 interacting and pathogenesis-related protein 5), which interacted
      with GhZFP1, were isolated. * GhZFP1 contains two typical zinc finger motifs
      (Cx8Cx5Cx3H and Cx5Cx4Cx3H), a putative nuclear export sequence (NES) and a
      potential nuclear localization signal (NLS). Transient expression analysis using
      a GhZFP1::GFP fusion gene in onion epidermal cells indicated a nuclear
      localization for GhZFP1. RNA blot analysis showed that the GhZFP1 transcript was
      induced by salt (NaCl), drought and salicylic acid (SA). The regions in GhZFP1
      that interact with GZIRD21A and GZIPR5 were identified using truncation
      mutations. * Overexpression of GhZFP1 in transgenic tobacco enhanced tolerance to
      salt stress and resistance to Rhizoctonia solani. Therefore, it appears that
      GhZFP1 might be involved as an important regulator in plant responses to abiotic
      and biotic stresses.

PMID- 19402880
TI  - Copper homeostasis.
AB  - Copper (Cu) is a cofactor in proteins that are involved in electron transfer
      reactions and is an essential micronutrient for plants. Copper delivery is
      accomplished by the concerted action of a set of evolutionarily conserved
      transporters and metallochaperones. As a result of regulation of transporters in
      the root and the rarity of natural soils with high Cu levels, very few plants in
      nature will experience Cu in toxic excess in their tissues. However, low Cu
      bioavailability can limit plant productivity and plants have an interesting
      response to impending Cu deficiency, which is regulated by an evolutionarily
      conserved master switch. When Cu supply is insufficient, systems to increase
      uptake are activated and the available Cu is utilized with economy. A number of
      Cu-regulated small RNA molecules, the Cu-microRNAs, are used to downregulate Cu
      proteins that are seemingly not essential. On low Cu, the Cu-microRNAs are
      upregulated by the master Cu-responsive transcription factor SPL7, which also
      activates expression of genes involved in Cu assimilation. This regulation allows
      the most important proteins, which are required for photo-autotrophic growth, to
      remain active over a wide range of Cu concentrations and this should broaden the
      range where plants can thrive.

PMID- 19402881
TI  - The adaptive significance of ontogenetic changes in physiology: a test in Avena
      barbata.
AB  - Physiological changes with ontogeny are common in plants. Although ontogenetic
      changes are hypothesized to improve plant function, their adaptive significance
      has rarely been tested. Here, we estimated phenotypic selection on ontogenetic
      change in photosynthesis (A) and stomatal conductance (g(s)) of Avena barbata. We
      tested whether ontogenetic changes in A and g(s) increased fitness in wet and dry
      soil environments. To determine whether evolution in response to this selection
      would be constrained, we estimated the heritability of ontogenetic change in
      physiology, as well as cross-environment genetic correlations. Ontogenetic change
      in A, but not g(s), was adaptive in the wet soil environment; plants that
      maintained or increased A from the prereproductive to the reproductive phase had
      higher fitness. In the dry soil environment, ontogenetic change in A and g(s) was
      adaptively neutral. We detected significant genetic variation for ontogenetic
      change in A and g(s), but no cross-environment genetic correlations, suggesting
      that the evolution of these traits would not be genetically constrained. We
      demonstrate that ontogenetic changes in physiological traits can increase fitness
      but the adaptive value of these changes varies among traits and environments.

PMID- 19402882
TI  - Evolution of stomatal responsiveness to CO(2) and optimization of water-use
      efficiency among land plants.
AB  - The stomata of angiosperms respond to changes in ambient atmospheric
      concentrations of CO(2) (C(a)) in ways that appear to optimize water-use
      efficiency. It is unknown where in the history of land plants this important
      stomatal control mechanism evolved. Here, we test the hypothesis that major
      clades of plants have distinct stomatal sensitivities to C(a) reflecting a
      relatively recent evolution of water-use optimization in derived angiosperms.
      Responses of stomatal conductance (g(s)) to step changes between elevated,
      ambient and low C(a) (600, 380 and 100 micromol mol(-1), respectively) were
      compared in a phylogenetically and ecologically diverse range of higher
      angiosperms, conifers, ferns and lycopods. All species responded to low C(a) by
      increasing g(s) but only angiosperm stomata demonstrated a significant closing
      response when C(a) was elevated to 600 micromol mol(-1). As a result, angiosperms
      showed significantly greater increases in water-use efficiency under elevated
      C(a) than the other lineages. The data suggest that the angiosperms have
      mechanisms for detecting and responding to increases in C(a) that are absent from
      earlier diverging lineages, and these mechanisms impart a greater capacity to
      optimize water-use efficiency.

PMID- 19402883
TI  - Two anion transporters AtClCa and AtClCe fulfil interconnecting but not redundant
      roles in nitrate assimilation pathways.
AB  - * In plants, the knowledge of the molecular identity and functions of anion
      channels are still very limited, and are almost restricted to the large ChLoride
      Channel (CLC) family. In Arabidopsis thaliana, some genetic evidence has
      suggested a role for certain AtCLC protein members in the control of plant
      nitrate levels. In this context, AtClCa has been demonstrated to be involved in
      nitrate transport into the vacuole, thereby participating in cell nitrate
      homeostasis. * In this study, analyses of T-DNA insertion mutants within the
      AtClCa and AtClCe genes revealed common phenotypic traits: a lower endogenous
      nitrate content; a higher nitrite content; a reduced nitrate influx into the
      root; and a decreased expression of several genes encoding nitrate transporters.
      * This set of nitrate-related phenotypes, displayed by clca and clce mutant
      plants, showed interconnecting roles of AtClCa and AtClCe in nitrate homeostasis
      involving two different endocellular membranes. * In addition, it revealed cross
      talk between two nitrate transporter families participating in nitrate
      assimilation pathways. The contribution to nitrate homeostasis at the cellular
      level of members of these different families is discussed.

PMID- 19402884
TI  - Regional block versus general anaesthesia for caesarean section and neonatal
      outcomes: a population-based study.
AB  - BACKGROUND: Anaesthesia guidelines recommend regional anaesthesia for most
      caesarean sections due to the risk of failed intubation and aspiration with
      general anaesthesia. However, general anaesthesia is considered to be safe for
      the foetus, based on limited evidence, and is still used for caesarean sections.
      METHODS: Cohorts of caesarean sections by indication (that is, planned repeat
      caesarean section, failure to progress, foetal distress) were selected from the
      period 1998 to 2004 (N = 50,806). Deliveries performed under general anaesthesia
      were compared with those performed under spinal or epidural, for the outcomes of
      neonatal intubation and 5-minute Apgar (Apgar5) <7. RESULTS: The risk of adverse
      outcomes was increased for caesarean sections under general anaesthesia for all
      three indications and across all levels of hospital. The relative risks were
      largest for low-risk planned repeat caesarean deliveries: resuscitation with
      intubation relative risk was 12.8 (95% confidence interval 7.6, 21.7), and Apgar5
      <7 relative risk was 13.4 (95% confidence interval 9.2, 19.4). The largest
      absolute increase in risk was for unplanned caesareans due to foetal distress:
      there were five extra intubations per 100 deliveries and six extra Apgar5 <7 per
      100 deliveries. CONCLUSION: The infants most affected by general anaesthesia were
      those already compromised in utero, as evidenced by foetal distress. The
      increased rate of adverse neonatal outcomes should be weighed up when general
      anaesthesia is under consideration.

PMID- 19402885
TI  - Academic career in medicine: requirements and conditions for successful
      advancement in Switzerland.
AB  - BACKGROUND: Within the framework of a prospective cohort study of Swiss medical
      school graduates a sample of young physicians aspiring to an academic career were
      surveyed on their career support and barriers experienced up to their sixth year
      of postgraduate training. METHODS: Thirty-one junior academics took part in semi
      structured telephone interviews in 2007. The interview guideline focused on
      career paths to date, career support and barriers experienced, and
      recommendations for junior and senior academics. The qualitatively assessed data
      were evaluated according to Mayring's content analysis. Furthermore,
      quantitatively gained data from the total cohort sample on person- and career
      related characteristics were analyzed in regard to differences between the junior
      academics and cohort doctors who aspire to another career in medicine. RESULTS:
      Junior academics differ in terms of instrumentality as a person-related factor,
      and in terms of intrinsic career motivation and mentoring as career-related
      factors from cohort doctors who follow other career paths in medicine; they also
      show higher scores in the Career-Success Scale. Four types of career path could
      be identified in junior academics: (1) focus on basic sciences, (2) strong focus
      on research (PhD programs) followed by clinical training, (3) one to two years in
      research followed by clinical training, (4) clinical training and research in
      parallel. The interview material revealed the following categories of career
      supporting experience: making oneself out as a proactive junior physician,
      research resources provided by superior staff, and social network; statements
      concerning career barriers encompassed interference between clinical training and
      research activities, insufficient research coaching, and personality related
      barriers. Recommendations for junior academics focused on mentoring and
      professional networking, for senior academics on interest in human resource
      development and being role models. CONCLUSION: The conditions for an academic
      career in medicine in Switzerland appear to be difficult especially for those
      physicians combining research with clinical work. For a successful academic
      career it seems crucial to start with research activities right after graduation,
      and take up clinical training later in the career. Furthermore, special mentoring
      programs for junior academics should be implemented at all medical schools to
      give trainees more goal-oriented guidance in their career.

PMID- 19402886
TI  - Application of serum proteomics to the Women's Health Initiative conjugated
      equine estrogens trial reveals a multitude of effects relevant to clinical
      findings.
AB  - BACKGROUND: The availability of serum collections from the Women's Health
      Initiative (WHI) conjugated equine estrogens (CEE) randomized controlled trial
      provides an opportunity to test the potential of in-depth quantitative proteomics
      to uncover changes in the serum proteome related to CEE and to assess their
      relevance to trial findings, including elevations in the risk of stroke and
      venous thromboembolism and a reduction in fractures. METHODS: Five independent
      large scale quantitative proteomics analyses were performed, each comparing a set
      of pooled serum samples collected from 10 subjects, 1 year following initiation
      of CEE at 0.625 mg/d, relative to their baseline pool. A subset of proteins that
      exhibited increased levels with CEE by quantitative proteomics was selected for
      validation studies. RESULTS: Of 611 proteins quantified based on differential
      stable isotope labeling, the levels of 116 (19%) were changed after 1 year of CEE
      (nominal P < 0.05), while 64 of these had estimated false discovery rates <0.05.
      Most of the changed proteins were not previously known to be affected by CEE and
      had relevance to processes that included coagulation, metabolism, osteogenesis,
      inflammation, and blood pressure maintenance. To validate quantitative proteomic
      data, 14 proteins were selected for ELISA. Findings for ten - IGF1, IGFBP4,
      IGFBP1, IGFBP2, F10, AHSG, GC, CP, MMP2, and PROZ - were confirmed in the initial
      set of 50 subjects and further validated in an independent set of 50 additional
      subjects who received CEE. CONCLUSIONS: CEE affected a substantial fraction of
      the serum proteome, including proteins with relevance to findings from the WHI
      CEE trial related to cardiovascular disease and fracture. CLINICAL TRIALS
      REGISTRATION: ClinicalTrials.gov identifier: NCT00000611.

PMID- 19402887
TI  - Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and
      right ventricular hypertrophy in neonatal hyperoxic lung injury.
AB  - BACKGROUND: Phosphodiesterase-5 inhibition with sildenafil has been used to treat
      severe pulmonary hypertension and bronchopulmonary dysplasia (BPD), a chronic
      lung disease in very preterm infants who were mechanically ventilated for
      respiratory distress syndrome. METHODS: Sildenafil treatment was investigated in
      2 models of experimental BPD: a lethal neonatal model, in which rat pups were
      continuously exposed to hyperoxia and treated daily with sildenafil (50-150 mg/kg
      body weight/day; injected subcutaneously) and a neonatal lung injury-recovery
      model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days
      of recovery in room air and started sildenafil treatment on day 6 of hyperoxia
      exposure. Parameters investigated include survival, histopathology, fibrin
      deposition, alveolar vascular leakage, right ventricular hypertrophy, and
      differential mRNA expression in lung and heart tissue. RESULTS: Prophylactic
      treatment with an optimal dose of sildenafil (2 x 50 mg/kg/day) significantly
      increased lung cGMP levels, prolonged median survival, reduced fibrin deposition,
      total protein content in bronchoalveolar lavage fluid, inflammation and septum
      thickness. Treatment with sildenafil partially corrected the differential mRNA
      expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth
      factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung
      and of brain and c-type natriuretic peptides and the natriuretic peptide
      receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury
      recovery model we demonstrated improved alveolarization and angiogenesis by
      attenuating mean linear intercept and arteriolar wall thickness and increasing
      pulmonary blood vessel density, and right ventricular hypertrophy (RVH).
      CONCLUSION: Sildenafil treatment, started simultaneously with exposure to
      hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels,
      reduces the pulmonary inflammatory response, fibrin deposition and RVH, and
      stimulates alveolarization. Initiation of sildenafil treatment after hyperoxic
      lung injury and continued during room air recovery improves alveolarization and
      restores pulmonary angiogenesis and RVH in experimental BPD.

PMID- 19402888
TI  - The association between back pain and trunk posture of workers in a special
      school for the severe handicaps.
AB  - BACKGROUND: The present study aims to determine the time spent in different
      static trunk postures during a typical working day of workers in a special school
      for the severe handicaps. METHODS: Eighteen workers with low back pain (LBP) and
      fifteen asymptomatic workers were recruited. A cross-sectional design was
      employed to study the time spent in different static trunk postures which was
      recorded by a biaxial accelerometer attached to the T12 level of the back of the
      subjects. RESULTS: The results of ANCOVA revealed that subjects with LBP spent
      significantly longer percentage of time in static trunk posture when compared to
      normal (p < 0.05). It was also shown that they spent significantly longer time in
      trunk flexion for more than 10 degrees (p < 0.0125). CONCLUSION: An innovative
      method has been developed for continuous tracking of spinal posture, and this has
      potential for widespread applications in the workplace. The findings of the
      present investigation suggest that teachers in special schools are at increased
      risk of getting LBP. In order to minimise such risk, frequent postural change and
      awareness of work posture are recommended.

PMID- 19402889
TI  - Eligibility of patients with advanced non-small cell lung cancer for phase III
      chemotherapy trials.
AB  - BACKGROUND: Evidence that chemotherapy improves survival and quality of life in
      patients with stage IIIB & IV non small cell lung cancer (NSCLC) is based on
      large randomized controlled trials. The purpose of this study was to determine
      eligibility of patients with advanced NSCLC for major chemotherapy trials.
      METHODS: Physicians treating stage IIIB/IV NSCLC at Sydney Cancer Centre assessed
      patient eligibility for the E1594, SWOG9509 and TAX326 trials for patients
      presenting from October 2001 to December 2002. A review of the centre's registry
      was used to obtain missing data. RESULTS: 199 patients with advanced NSCLC were
      registered during the 14-month period. Characteristics of 100 patients were
      defined prospectively, 85 retrospectively: 77% males, median age 68 (range 32
      88), 64% stage IV disease. Only 35% met trial eligibility for E1594 and 28% for
      SWOG9509 and TAX326. Common reasons for ineligibility were: co-morbidities
      75(40%); ECOG Performance Status >or=2 72(39%); symptomatic brain metastasis
      15(8%); and previous cancers 21(11%). Many patients were ineligible by more than
      one criterion. CONCLUSION: The majority of patients with advanced NSCLC were
      ineligible for the large chemotherapy trials. The applicability of trial results
      to advanced lung cancer populations may be limited. Future trials should be
      conducted in a more representative population.

PMID- 19402890
TI  - Recent developments of acupuncture in Australia and the way forward.
AB  - Almost one in ten Australians has received acupuncture treatment by
      acupuncturists and/or medical doctors in private clinics. The majority of
      Australian health insurance funds offer rebates for acupuncture. Statutory
      regulations for acupuncture have been implemented in the State of Victoria,
      Australia. Six acupuncture degree courses have been approved by the Chinese
      Medicine Registration Board of Victoria and/or accredited by the Australian
      Acupuncture and Chinese Medicine Association. Furthermore, a number of clinical
      trials of acupuncture on allergic rhinitis, pain and women's health were carried
      out in Australia. Recent developments of acupuncture in Australia indicate that
      through adequate and appropriate evaluation, acupuncture begins to integrate into
      mainstream health care in Australia.

PMID- 19402891
TI  - Sharing clinical information across care settings: the birth of an integrated
      assessment system.
AB  - BACKGROUND: Population ageing, the emergence of chronic illness, and the shift
      away from institutional care challenge conventional approaches to assessment
      systems which traditionally are problem and setting specific. METHODS: From 2002,
      the interRAI research collaborative undertook development of a suite of
      assessment tools to support assessment and care planning of persons with chronic
      illness, frailty, disability, or mental health problems across care settings. The
      suite constitutes an early example of a "third generation" assessment system.
      RESULTS: The rationale and development strategy for the suite is described,
      together with a description of potential applications. To date, ten instruments
      comprise the suite, each comprising "core" items shared among the majority of
      instruments and "optional" items that are specific to particular care settings or
      situations. CONCLUSION: This comprehensive suite offers the opportunity for
      integrated multi-domain assessment, enabling electronic clinical records, data
      transfer, ease of interpretation and streamlined training.

PMID- 19402892
TI  - Distinct patterns of gene and protein expression elicited by organophosphorus
      pesticides in Caenorhabditis elegans.
AB  - BACKGROUND: The wide use of organophosphorus (OP) pesticides makes them an
      important public health concern. Persistent effects of exposure and the mechanism
      of neuronal degeneration are continuing issues in OP toxicology. To elucidate
      early steps in the mechanisms of OP toxicity, we studied alterations in global
      gene and protein expression in Caenorhabditis elegans exposed to OPs using
      microarrays and mass spectrometry. We tested two structurally distinct OPs
      (dichlorvos and fenamiphos) and employed a mechanistically different third
      neurotoxicant, mefloquine, as an out-group for analysis. Treatment levels used
      concentrations of chemical sufficient to prevent the development of 10%, 50% or
      90% of mid-vulval L4 larvae into early gravid adults (EGA) at 24 h after exposure
      in a defined, bacteria-free medium. RESULTS: After 8 h of exposure, the
      expression of 87 genes responded specifically to OP treatment. The abundance of
      34 proteins also changed in OP-exposed worms. Many of the genes and proteins
      affected by the OPs are expressed in neuronal and muscle tissues and are involved
      in lipid metabolism, cell adhesion, apoptosis/cell death, and detoxification.
      Twenty-two genes were differentially affected by the two OPs; a large proportion
      of these genes encode cytochrome P450s, UDP-glucuronosyl/UDP
      glucosyltransferases, or P-glycoproteins. The abundance of transcripts and the
      proteins they encode were well correlated. CONCLUSION: Exposure to OPs elicits a
      pattern of changes in gene expression in exposed worms distinct from that of the
      unrelated neurotoxicant, mefloquine. The functional roles and the tissue location
      of the genes and proteins whose expression is modulated in response to exposure
      is consistent with the known effects of OPs, including damage to muscle due to
      persistent hypercontraction, neuronal cell death, and phase I and phase II
      detoxification. Further, the two different OPs evoked distinguishable changes in
      gene expression; about half the differences are in genes involved in
      detoxification, likely reflecting differences in the chemical structure of the
      two OPs. Changes in the expression of a number of sequences of unknown function
      were also discovered, and these molecules could provide insight into novel
      mechanisms of OP toxicity or adaptation in future studies.

PMID- 19402893
TI  - An oral recombinant Salmonella enterica serovar Typhimurium mutant elicits
      systemic antigen-specific CD8+ T cell cytokine responses in mice.
AB  - BACKGROUND: The induction of antigen-specific CD8+ T cell cytokine responses
      against an attenuated, oral recombinant Salmonella enterica serovar Typhimurium
      vaccine expressing a green fluorescent protein (GFP) model antigen was
      investigated. A GFP expression plasmid was constructed in which the gfp gene was
      fused in-frame with the 5' domain of the Escherichia coli beta-galactosidase
      alpha-gene fragment with expression under the lac promoter. Groups of mice were
      orally immunized three times with the bacteria and systemic CD8+ T cell cytokine
      responses were evaluated. RESULTS: High level of the GFP model antigen was
      expressed by the recombinant Salmonella vaccine vector. Systemic GFP-specific
      CD8+ T cell cytokine (IFN-gamma and IL-4) immune responses were detected after
      mice were orally vaccinated with the bacteria. It was shown that 226 net IFN
      gamma and 132 net IL-4 GFP-specific SFUs/10e6 splenocytes were formed in an
      ELISPOT assay. The level of IFN-gamma produced by GFP peptide-stimulated cells
      was 65.2-fold above background (p < 0.05). The level of IL-4 produced by the
      cells was 10.4-fold above background (p < 0.05). CONCLUSION: These results
      suggested that a high expressing recombinant Salmonella vaccine given orally to
      mice would elicit antigen-specific CD8+ T cell responses in the spleen.
      Salmonella bacteria may, therefore, be used as potential mucosal vaccine vectors.

PMID- 19402894
TI  - Towards high-throughput molecular detection of Plasmodium: new approaches and
      molecular markers.
AB  - BACKGROUND: Several strategies are currently deployed in many countries in the
      tropics to strengthen malaria control toward malaria elimination. To measure the
      impact of any intervention, there is a need to detect malaria properly. Mostly,
      decisions still rely on microscopy diagnosis. But sensitive diagnosis tools
      enabling to deal with a large number of samples are needed. The molecular
      detection approach offers a much higher sensitivity, and the flexibility to be
      automated and upgraded. METHODS: Two new molecular methods were developed:
      dot18S, a Plasmodium-specific nested PCR based on the 18S rRNA gene followed by
      dot-blot detection of species by using species-specific probes and CYTB, a
      Plasmodium-specific nested PCR based on cytochrome b gene followed by species
      detection using SNP analysis. The results were compared to those obtained with
      microscopic examination and the "standard" 18S rRNA gene based nested PCR using
      species specific primers. 337 samples were diagnosed. RESULTS: Compared to the
      microscopy the three molecular methods were more sensitive, greatly increasing
      the estimated prevalence of Plasmodium infection, including P. malariae and P.
      ovale. A high rate of mixed infections was uncovered with about one third of the
      villagers infected with more than one malaria parasite species. Dot18S and CYTB
      sensitivity outranged the "standard" nested PCR method, CYTB being the most
      sensitive. As a consequence, compared to the "standard" nested PCR method for the
      detection of Plasmodium spp., the sensitivity of dot18S and CYTB was respectively
      95.3% and 97.3%. Consistent detection of Plasmodium spp. by the three molecular
      methods was obtained for 83% of tested isolates. Contradictory results were
      mostly related to detection of Plasmodium malariae and Plasmodium ovale in mixed
      infections, due to an "all-or-none" detection effect at low-level parasitaemia.
      CONCLUSION: A large reservoir of asymptomatic infections was uncovered using the
      molecular methods. Dot18S and CYTB, the new methods reported herein are highly
      sensitive, allow parasite DNA extraction as well as genus- and species-specific
      diagnosis of several hundreds of samples, and are amenable to high-throughput
      scaling up for larger sample sizes. Such methods provide novel information on
      malaria prevalence and epidemiology and are suited for active malaria detection.
      The usefulness of such sensitive malaria diagnosis tools, especially in low
      endemic areas where eradication plans are now on-going, is discussed in this
      paper.

PMID- 19402895
TI  - Cancer screening in a middle-aged general population: factors associated with
      practices and attitudes.
AB  - BACKGROUND: The aim of this study was to identify factors associated with cancer
      screening practices and with general attitudes toward cancer screening in a
      general population. METHODS: Mailed survey of 30-60 year old residents of Geneva,
      Switzerland, that included questions about screening for five cancers (breast,
      cervix uteri, prostate, colon, skin) in the past 3 years, attitudes toward
      screening, health care use, preventive behaviours and socio-demographic
      characteristics. Cancer screening practice was dichotomised as having done at
      least one screening test in the past 3 years versus none. RESULTS: The survey
      response rate was 49.3% (2301/4670). More women than men had had at least one
      cancer screening test in the past 3 years (83.2% vs 34.5%, p < 0.001). A majority
      of women had had a cervical smear (76.6%) and a mammography (age 30-49: 35.0%;
      age 50 and older: 90.3%); and 55.1% of men 50-60 years old had been screened for
      prostate cancer. Other factors associated with screening included older age,
      higher income, a doctor visit in the past 6 months, reporting a greater number of
      preventive behaviours and a positive attitude toward screening. Factors linked
      with positive attitudes included female gender, higher level of education,
      gainful employment, higher income, a doctor visit in the past 6 months and a
      personal history of cancer. CONCLUSION: Attitudes play an important role in
      cancer screening practices among middle-aged adults in the general population,
      independent of demographic variables (age and sex) that determine in part
      screening recommendations. Negative attitudes were the most frequent among men
      and the most socio-economically disadvantaged. The moderate participation rate
      raises the possibility of selection bias.

PMID- 19402897
TI  - Effects of 9cis,11trans and 10trans,12cis CLA on osteoclast formation and
      activity from human CD14+ monocytes.
AB  - BACKGROUND: Mixed CLA isomers variably affect bone resorption in animals and
      decrease osteoclast formation and activity in murine osteoclasts. These variable
      effects may be due to the different isomers present in commercial preparations of
      CLA, and the effects of the predominant individual isomers, 9cis,11trans (9,11)
      and 10trans,12cis (10,12) CLA are not clear. The objectives of this study were to
      determine the effects of the individual CLA isomers on osteoclast formation and
      activity from human CD14+ monocytes, and to determine whether any changes are
      accompanied by changes in cathepsin K, matrix metalloproteinase-9 (MMP-9),
      receptor activator of NF-kappaB (RANK) and tumour necrosis factor alpha
      (TNFalpha) gene expression. Osteoclasts were identified as TRAP+ multinucleated
      cells. Osteoclast activity was quantified by the amount of TRAP in the cultured
      media. RESULTS: At 50 microM, 9,11 CLA inhibited osteoclast formation by
      approximately 70%, and both 9,11 and 10,12 CLA decreased osteoclast activity by
      approximately 85-90%. Both isomers inhibited cathepsin K (50 microM 9,11 by
      approximately 60%; 10,12 by approximately 50%) and RANK (50 microM 9,11 by
      approximately 85%; 50 microM 10,12 by approximately 65%) expression, but had no
      effect on MMP-9 or TNFalpha expression. CONCLUSION: 9,11 CLA inhibits osteoclast
      formation and activity from human cells, suggesting that this isomer may prevent
      bone resorption in humans. Although 10,12 CLA did not significantly reduce
      osteoclast formation, it reduced osteoclast activity and cathepsin K and RANK
      expression, suggesting that this isomer may also affect bone resorption.

PMID- 19402898
TI  - Rasch scaling procedures for informing development of a valid Fetal Surveillance
      Education Program multiple-choice assessment.
AB  - BACKGROUND: It is widely recognised that deficiencies in fetal surveillance
      practice continue to contribute significantly to the burden of adverse outcomes.
      This has prompted the development of evidence-based clinical practice guidelines
      by the Royal Australian and New Zealand College of Obstetricians and
      Gynaecologists and an associated Fetal Surveillance Education Program to deliver
      the associated learning. This article describes initial steps in the validation
      of a corresponding multiple-choice assessment of the relevant educational
      outcomes through a combination of item response modelling and expert judgement.
      METHODS: The Rasch item response model was employed for item and test analysis
      and to empirically derive the substantive interpretation of the assessment
      variable. This interpretation was then compared to the hierarchy of competencies
      specified a priori by a team of eight subject-matter experts. Classical Test
      Theory analyses were also conducted. RESULTS: A high level of agreement between
      the hypothesised and derived variable provided evidence of construct validity.
      Item and test indices from Rasch analysis and Classical Test Theory analysis
      suggested that the current test form was of moderate quality. However, the
      analyses made clear the required steps for establishing a valid assessment of
      sufficient psychometric quality. These steps included: increasing the number of
      items from 40 to 50 in the first instance, reviewing ineffective items, targeting
      new items to specific content and difficulty gaps, and formalising the assessment
      blueprint in light of empirical information relating item structure to item
      difficulty. CONCLUSION: The application of the Rasch model for criterion
      referenced assessment validation with an expert stakeholder group is herein
      described. Recommendations for subsequent item and test construction are also
      outlined in this article.

PMID- 19402896
TI  - Postprandial hyperglycemia as an etiological factor in vascular failure.
AB  - Postprandial hyperglycemia is characterized by hyperglycemic spikes that induce
      endothelial dysfunction, inflammatory reactions and oxidative stress, which may
      lead to progression of atherosclerosis and occurrence of cardiovascular events.
      Emerging data indicate that postprandial hyperglycemia or even impaired glucose
      tolerance may predispose to progression of atherosclerosis and cardiovascular
      events. There is evidence that postprandial hyperglycemia, but not fasting
      hyperglycemia, independently predicts the occurrence of cardiovascular events. We
      proposed a concept of 'vascular failure' as a comprehensive syndrome of vascular
      dysfunction extending from risk factors to advanced atherosclerotic disease.
      Postprandial hyperglycemia is therefore one of the very important
      pathophysiological states contributing to vascular failure. Accordingly,
      controlling postprandial hyperglycemia should be the focus of future clinical
      investigation as a potential target for preventing vascular failure.

PMID- 19402899
TI  - Cardiovascular magnetic resonance findings in a case of Danon disease.
AB  - Danon disease is a rare X-linked dominant lysosomal glycogen storage disease that
      can lead to severe ventricular hypertrophy and heart failure. We report a case of
      Danon disease with cardiac involvement evaluated with cardiovascular magnetic
      resonance, including late gadolinium enhancement and perfusion studies.

PMID- 19402900
TI  - Validation of a prognostic scoring system for locally recurrent nasopharyngeal
      carcinoma treated by stereotactic radiosurgery.
AB  - BACKGROUND: Selection of patients with local failure of nasopharyngeal carcinoma
      (NPC) for appropriate type of salvage treatment can be difficult due to the lack
      of data on comparative efficacy of different salvage treatments. The purpose of
      the present study was to validate a previously published prognostic scoring
      system for local failures of NPC treated by radiosurgery based on reported
      results in the literature. METHODS: A literature search yielded 3 published
      reports on the use of radiosurgery as salvage treatment of NPC that contained
      sufficient clinical information for validation of the scoring system. Prognostic
      scores of 18 patients from these reports were calculated and actuarial survival
      rates were estimated and compared to the original cohort used to design the
      prognostic scoring system. The area under the receiver operating characteristic
      curve was also determined and compared between the current and original patient
      groups. RESULTS: The calculated prognostic scores ranged from 0.32 to 1.21, with
      15 patients assigned to the poor prognostic group and 3 to the intermediate
      prognostic group. The actuarial 3-year survival rates in the intermediate and
      poor prognostic groups were 67% and 0%, respectively. These results were
      comparable to the observed 3-year survival rates of 74% and 23% in the
      intermediate and poor prognostic group in the original reports. The area under
      the receiver operating characteristic curve for the current patient group was
      0.846 which was similar to 0.841 in the original group. CONCLUSION: The
      previously published prognostic scoring system demonstrated good prediction of
      treatment outcome after radiosurgery in a small group of NPC patients with poor
      prognosis. Prospective study to validate the scoring system is currently being
      carried out in our institution.

PMID- 19402901
TI  - A SNaPshot assay for the rapid and simple detection of four common hotspot codon
      mutations in the PIK3CA gene.
AB  - BACKGROUND: Activating mutations in the PIK3CA gene have been identified in a
      variety of human malignancies and are commonly detected in hotspot codons located
      in the helical and kinase domains in exons 9 and 20. Existing methodologies for
      the detection of PIK3CA mutations are time-consuming and/or expensive. In the
      present study we describe the first application of a PIK3CA SNaPshot assay to the
      screening of frequent mutations in these exons. FINDINGS: A SNaPshot assay for
      the simultaneous detection of four frequent PIK3CA hotspot mutations (E542K,
      E545G, E545K and H1047R) has been developed and evaluated. The assay combines
      multiplex PCR amplification with a multiplex primer extension assay to allow
      targeted detection of all four mutations in one reaction. The method was tested
      using samples that had previously been analysed for mutations by high-resolution
      melting analysis and sequencing. All mutations detected were concordant and no
      false positive results were obtained. Sensitivity tests showed that the SNaPshot
      assay could detect mutant DNA when it represents 5-10% of the total DNA present.
      The application of the method to the analysis of DNAs extracted from formalin
      fixed paraffin-embedded samples was also demonstrated. CONCLUSION: The SNaPshot
      assay described here offers a fast, sensitive, inexpensive and specific approach
      to the analysis of frequent PIK3CA mutations in both fresh and archival patient
      samples.

PMID- 19402902
TI  - Open cervical lymph node biopsy for head and neck cancers: any benefit?
AB  - BACKGROUND: Most patients with head and neck cancers in our environment present
      late and usually first to the general surgeons whose practice is to subject these
      patients to open cervical lymph node biopsy without a prior examination under
      anesthesia and endoscopic biopsy from the primary tumor site in order to obtain a
      histological diagnosis. This paper presents the influence of open cervical lymph
      node biopsy on the clinical outcome of patients with head and neck cancers in our
      environment. METHODS: This is a ten-year retrospective review of patients with
      head and neck cancers in the Jos University Teaching Hospital, Jos, Nigeria.
      RESULTS: Eighty nine patients aged between 23 and 78 years had head and neck
      cancers with 38/89 (42.7%) patients having cervical lymphadenopathy at
      presentation and these initially presented to the general surgeons. Twenty six
      (68.4%) patients had open cervical lymph node biopsy and 12/38 (31.6%) patients
      had FNAB. Eleven (28.9%) patients presented to the otolaryngology unit 6 months
      after they presented to the general surgeons and 27 (71.1%) patients beyond 6
      months. Nine deaths were recorded. Ten patients were lost to follow-up.
      CONCLUSION: All patients with head and neck lymphadenopathy who present to any
      physician for diagnostic examination should undergo formal ENT staging and FNAB
      to avoid the problems of tumor spread and the reduction in consequent prognosis.

PMID- 19402904
TI  - Evaluation of dog owners' perceptions concerning radiation therapy.
AB  - BACKGROUND: External radiation therapy (RT) has been available for small animals
      in Sweden since 2006. This study was designed to obtain information on owner
      experiences and perceptions related to RT of cancer in their dogs. Another survey
      was used to determine the attitudes about use of RT in a group of Swedish
      veterinarians. Their responses were analyzed and compared to their level of
      knowledge of oncology and RT. METHODS: Owners of all dogs (n = 23) who had
      undergone RT for malignancy at Jonkoping Small Animal Hospital between March 2006
      to September 2007 were interviewed. A questionnaire was given to a selected group
      of veterinarians. RESULTS: All 23 owners responded. All owners thought that their
      dog did well during RT and most that their dog was also fine during the following
      phase when acute RT-related skin reactions occur and heal. Three owners stated
      that their dog had pain that negatively impacted quality of life because of
      radiation dermatitis. Five owners reported that RT positively impacted quality of
      life of the dog during the first weeks after RT because palliation was achieved.
      The owners were not disturbed by the efforts required of them. All but one owner
      (22 of 23) stated that they would make the same decision about RT again if a
      similar situation occurred. The most important factor for this decision was the
      chance to delay occurrence of tumour-related discomfort. The chance for cure was
      of less importance but still essential, followed by expected side effects. Time
      commitments, travel, number of treatments required and financial cost; all had
      low impact. The veterinarian survey showed that less background knowledge of
      small animal oncology/RT was associated with more negative expectations of RT for
      small animals. CONCLUSION: The results show that for these owners, RT was a
      worthwhile treatment modality and that the discomfort for the dog was manageable
      and acceptable relative to the benefits. Improved continuing education about
      small animal RT in Sweden will likely result in increased evidence-based and
      positive treatment recommendations concerning RT by veterinarians.

PMID- 19402903
TI  - Ultrasound imaging of the lactating breast: methodology and application.
AB  - Ultrasound imaging has been used extensively to detect abnormalities of the non
      lactating breast. In contrast, the use of ultrasound for the investigation of
      pathology of the lactating breast is limited. Recent studies have re-examined the
      anatomy of the lactating breast highlighting features unique to this phase of
      breast development. These features should be taken into consideration along with
      knowledge of common lactation pathologies in order to make an accurate diagnosis
      when examining the lactating breast. Scanning techniques and ultrasound
      appearances of the normal lactating breast will be contrasted to those of the non
      lactating breast. In addition ultrasound characteristics of common pathologies
      encountered during lactation will be described.

PMID- 19402905
TI  - A randomised controlled trial of a community-based healthy lifestyle program for
      overweight and obese adolescents: the Loozit study protocol.
AB  - BACKGROUND: There is a need to develop sustainable and clinically effective
      weight management interventions that are suitable for delivery in community
      settings where the vast majority of overweight and obese adolescents should be
      treated. This study aims to evaluate the effect of additional therapeutic contact
      as an adjunct to the Loozit group program -- a community-based, lifestyle
      intervention for overweight and lower grade obesity in adolescents. The
      additional therapeutic contact is provided via telephone coaching and either
      mobile phone Short Message Service or electronic mail, or both. METHODS AND
      DESIGN: The study design is a two-arm randomised controlled trial that aims to
      recruit 168 overweight and obese 13-16 year olds (Body Mass Index z-score 1.0 to
      2.5) in Sydney, Australia. Adolescents with secondary causes of obesity or
      significant medical illness are excluded. Participants are recruited via schools,
      media coverage, health professionals and several community organisations. Study
      arm one receives the Loozit group weight management program (G). Study arm two
      receives the same Loozit group weight management program plus additional
      therapeutic contact (G+ATC). The 'G' intervention consists of two phases. Phase 1
      involves seven weekly group sessions held separately for adolescents and their
      parents. This is followed by phase 2 that involves a further seven group sessions
      held regularly, for adolescents only, until two years follow-up. Additional
      therapeutic contact is provided to adolescents in the 'G+ATC' study arm
      approximately once per fortnight during phase 2 only. Outcome measurements are
      assessed at 2, 12 and 24 months post-baseline and include: BMI z-score, waist z
      score, metabolic profile indicators, physical activity, sedentary behaviour,
      eating patterns, and psychosocial well-being. DISCUSSION: The Loozit study is the
      first randomised controlled trial of a community-based adolescent weight
      management intervention to incorporate additional therapeutic contact via a
      combination of telephone coaching, mobile phone Short Message Service, and
      electronic mail. If shown to be successful, the Loozit group weight management
      program with additional therapeutic contact has the potential to be readily
      translatable to a range of health care settings. TRIAL REGISTRATION: The protocol
      for this study is registered with the Australian Clinical Trials Registry
      (ACTRNO12606000175572).

PMID- 19402906
TI  - Role of hepatitis B surface antigen in the development of hepatocellular
      carcinoma: regulation of lymphoid enhancer-binding factor 1.
AB  - BACKGROUND: There are around 350 million of hepatitis B surface antigen (HBsAg)
      carriers worldwide, and among them, high risk of developing hepatocellular
      carcinoma (HCC) has been identified by epidemiological studies. To date, the
      molecular role of HBsAg in HCC development has not been fully studied. We have
      previously reported that in cell cultures, HBsAg up-regulated the expression of
      lymphoid enhancer-binding factor 1 (LEF-1), a key component of the Wnt pathway.
      In this study we aimed to study this effect of HBsAg on LEF-1 in the development
      of HCC. METHODS: Expression of HBsAg, LEF-1 and its downstream effector genes
      were compared among 30 HCCs, their peritumor tissue counterparts and 9 normal
      control liver tissues by quantitative real-time PCR. In addition,
      immunohistochemical staining studies on HBsAg and LEF-1 expression were conducted
      among these samples. RESULTS: The expression of LEF-1 was compared between 13
      HBsAg positive HCC tissues and 17 HBsAg negative HCC tissues. Simultaneous
      detection of LEF-1 and HBsAg was observed in HBsAg positive HCC tissues and,
      additionally, the simultaneous detection of HBsAg and LEF-1 was more pronounced
      in peritumor tissues, compared to that in the tumor tissues. The distribution of
      cellular LEF-1 in peritumor tissues was predominantly in the cytoplasm; while LEF
      1 in the tumor tissues was located either exclusively in the nucleus or both in
      the nucleus and cytoplasm. By real-time PCR, the expression levels of LEF-1
      downstream effector genes cyclin D1 and c-myc were higher in peritumor cells
      compared to that of the tumor cells. However, a 38 kDa truncated isoform of LEF
      1, rather than the 55 kDa wild-type LEF-1, was significantly elevated in the
      HBsAg positive tumor cells. CONCLUSION: Data indicate that deregulation of the
      Wnt pathway by HBsAg occurred in HBV-associated HCCs, but was more pronounced in
      the peritumor cells. It is speculated that HBsAg could stimulate proliferation
      and functional modification of hepatocytes via LEF-1 through the Wnt pathway at
      the pre-malignant stage.

PMID- 19402907
TI  - Next-generation pyrosequencing of gonad transcriptomes in the polyploid lake
      sturgeon (Acipenser fulvescens): the relative merits of normalization and
      rarefaction in gene discovery.
AB  - BACKGROUND: Next-generation sequencing technologies have been applied most often
      to model organisms or species closely related to a model. However, these methods
      have the potential to be valuable in many wild organisms, including those of
      conservation concern. We used Roche 454 pyrosequencing to characterize gene
      expression in polyploid lake sturgeon (Acipenser fulvescens) gonads. RESULTS:
      Titration runs on a Roche 454 GS-FLX produced more than 47,000 sequencing reads.
      These reads represented 20,741 unique sequences that passed quality control (mean
      length = 186 bp). These were assembled into 1,831 contigs (mean contig depth =
      4.1 sequences). Over 4,000 sequencing reads (approximately 19%) were assigned
      gene ontologies, mostly to protein, RNA, and ion binding. A total of 877
      candidate SNPs were identified from > 50 different genes. We employed an
      analytical approach from theoretical ecology (rarefaction) to evaluate depth of
      sequencing coverage relative to gene discovery. We also considered the relative
      merits of normalized versus native cDNA libraries when using next-generation
      sequencing platforms. Not surprisingly, fewer genes from the normalized libraries
      were rRNA subunits. Rarefaction suggests that normalization has little influence
      on the efficiency of gene discovery, at least when working with thousands of
      reads from a single tissue type. CONCLUSION: Our data indicate that titration
      runs on 454 sequencers can characterize thousands of expressed sequence tags
      which can be used to identify SNPs, gene ontologies, and levels of gene
      expression in species of conservation concern. We anticipate that rarefaction
      will be useful in evaluations of gene discovery and that next-generation
      sequencing technologies hold great potential for the study of other non-model
      organisms.

PMID- 19402908
TI  - Is primary care a neglected piece of the jigsaw in ensuring optimal stroke care?
      Results of a national study.
AB  - BACKGROUND: Stroke is a major cause of mortality and morbidity with potential for
      improved care and prevention through general practice. A national survey was
      undertaken to determine current resources and needs for optimal stroke prevention
      and care. METHODS: Postal survey of random sample of general practitioners
      undertaken (N = 204; 46% response). Topics included practice organisation,
      primary prevention, acute management, secondary prevention, long-term care and
      rehabilitation. RESULTS: Service organisation for both primary and secondary
      prevention was poor. Home management of acute stroke patients was used at some
      stage by 50% of responders, accounting for 7.3% of all stroke patients. Being in
      a structured cardiovascular management scheme, a training practice, a larger
      practice, or a practice employing a practice nurse were associated with
      structures and processes likely to support stroke prevention and care.
      CONCLUSION: General practices were not fulfilling their potential to provide
      stroke prevention and long-term management. Systems of structured stroke
      management in general practice are essential to comprehensive national programmes
      of stroke care.

PMID- 19402909
TI  - Acetaldehyde and hexanaldehyde from cultured white cells.
AB  - BACKGROUND: Noninvasive detection of innate immune function such as the
      accumulation of neutrophils remains a challenge in many areas of clinical
      medicine. We hypothesized that granulocytes could generate volatile organic
      compounds. METHODS: To begin to test this, we developed a bioreactor and
      analytical GC-MS system to accurately identify and quantify gases in trace
      concentrations (parts per billion) emitted solely from cell/media culture. A
      human promyelocytic leukemia cell line, HL60, frequently used to assess
      neutrophil function, was grown in serum-free medium. RESULTS: HL60 cells released
      acetaldehyde and hexanaldehyde in a time-dependent manner. The mean +/- SD
      concentration of acetaldehyde in the headspace above the cultured cells following
      4-, 24- and 48-h incubation was 157 +/- 13 ppbv, 490 +/- 99 ppbv, 698 +/- 87
      ppbv. For hexanaldehyde these values were 1 +/- 0.3 ppbv, 8 +/- 2 ppbv, and 11 +/
      2 ppbv. In addition, our experimental system permitted us to identify
      confounding trace gas contaminants such as styrene. CONCLUSION: This study
      demonstrates that human immune cells known to mimic the function of innate immune
      cells, like neutrophils, produce volatile gases that can be measured in vitro in
      trace amounts.

PMID- 19402911
TI  - A rapid method of fruit cell isolation for cell size and shape measurements.
AB  - BACKGROUND: Cell size is a structural component of fleshy fruit, contributing to
      important traits such as fruit size and texture. There are currently a number of
      methods for measuring cell size; most rely either on tissue sectioning or
      digestion of the tissue with cell wall degrading enzymes or chemicals to release
      single cells. Neither of these approaches is ideal for assaying large fruit
      numbers as both require a considerable time to prepare the tissue, with current
      methods of cell wall digestions taking 24 to 48 hours. Additionally, sectioning
      can lead to a measurement of a plane that does not represent the widest point of
      the cell. RESULTS: To develop a more rapid way of measuring fruit cell size we
      have developed a protocol that solubilises pectin in the middle lamella of the
      plant cell wall releasing single cells into a buffered solution. Gently boiling
      small fruit samples in a 0.05 M Na2CO3 solution, osmotically balanced with 0.3 M
      mannitol, produced good cell separation with little cellular damage in less than
      30 minutes. The advantage of combining a chemical treatment with boiling is that
      the cells are rapidly killed. This stopped cell shape changes that could
      potentially occur during separation. With this method both the rounded and
      angular cells of the apple cultivars SciRos 'Pacific Rose' and SciFresh 'Jazz'
      were observed in the separated cells. Using this technique, an in-depth analysis
      was performed measuring cell size from 5 different apple cultivars. Cell size was
      measured using the public domain ImageJ software. For each cultivar a minimum of
      1000 cells were measured and it was found that each cultivar displayed a
      different distribution of cell size. Cell size within cultivars was similar and
      there was no correlation between flesh firmness and cell size. This protocol was
      tested on tissue from other fleshy fruit including tomato, rock melon and
      kiwifruit. It was found that good cell separation was achieved with flesh tissue
      from all these fruit types, showing a broad utility to this protocol. CONCLUSION:
      We have developed a method for isolating single cells from fleshy fruit that
      reduces the time needed for fruit cell separation. This method was used to
      demonstrate differences in cell size and shape for 5 different apple cultivars.
      While firmness between the different cultivars is independent of cell size,
      apples with more angular cells appear to be firmer.

PMID- 19402910
TI  - Antimicrobial effect of farnesol, a Candida albicans quorum sensing molecule, on
      Paracoccidioides brasiliensis growth and morphogenesis.
AB  - BACKGROUND: Farnesol is a sesquiterpene alcohol produced by many organisms, and
      also found in several essential oils. Its role as a quorum sensing molecule and
      as a virulence factor of Candida albicans has been well described. Studies
      revealed that farnesol affect the growth of a number of bacteria and fungi,
      pointing to a potential role as an antimicrobial agent. METHODS: Growth assays of
      Paracoccidioides brasiliensis cells incubated in the presence of different
      concentrations of farnesol were performed by measuring the optical density of the
      cultures. The viability of fungal cells was determined by MTT assay and by
      counting the colony forming units, after each farnesol treatment. The effects of
      farnesol on P. brasiliensis dimorphism were also evaluated by optical microscopy.
      The ultrastructural morphology of farnesol-treated P. brasiliensis yeast cells
      was evaluated by transmission and scanning electron microscopy. RESULTS: In this
      study, the effects of farnesol on Paracoccidioides brasiliensis growth and
      dimorphism were described. Concentrations of this isoprenoid ranging from 25 to
      300 microM strongly inhibited P. brasiliensis growth. We have estimated that the
      MIC of farnesol for P. brasiliensis is 25 microM, while the MLC is around 30
      microM. When employing levels which don't compromise cell viability (5 to 15
      microM), it was shown that farnesol also affected the morphogenesis of this
      fungus. We observed about 60% of inhibition in hyphal development following P.
      brasiliensis yeast cells treatment with 15 microM of farnesol for 48 h. At these
      farnesol concentrations we also observed a significant hyphal shortening.
      Electron microscopy experiments showed that, despite of a remaining intact cell
      wall, P. brasiliensis cells treated with farnesol concentrations above 25 microM
      exhibited a fully cytoplasmic degeneration. CONCLUSION: Our data indicate that
      farnesol acts as a potent antimicrobial agent against P. brasiliensis. The
      fungicide activity of farnesol against this pathogen is probably associated to
      cytoplasmic degeneration. In concentrations that do not affect fungal viability,
      farnesol retards the germ-tube formation of P. brasiliensis, suggesting that the
      morphogenesis of this fungal is controlled by environmental conditions.

PMID- 19402912
TI  - The Rourke Baby Record Infant/Child Maintenance Guide: do doctors use it, do they
      find it useful, and does using it improve their well-baby visit records?
AB  - BACKGROUND: The Rourke Baby Record (RBR) - http://www.rourkebabyrecord.ca - is a
      freely available evidence-based structured form for child health surveillance
      from zero to five years. Family physicians/general practitioners (FP/GPs) doing
      office based well-baby care in three Ontario Canada cities (London, Ottawa, and
      Toronto) were randomly sampled to study the prevalence and utility of the RBR and
      documentation of well-baby visits. METHODS: Database with telephone confirmation
      was conducted to assess the prevalence of use of the RBR. Study Part 1:
      Questionnaire mailed to a random sample of 100 RBR users. Outcome measures were
      utility of, helpfulness of, and suggestions for the RBR. Descriptive analysis was
      employed. Study Part 2: Retrospective chart review of well-baby visits by 38
      FP/GPs using student t-tests and factor analysis. Outcome measures were well-baby
      visit documentation of growth, nutrition, safety issues, developmental
      milestones, physical examination, and overall comprehensiveness. RESULTS: The RBR
      was used by 78.5% (402/512) of successfully contacted FP/GPs who did well-baby
      care in these 3 cities. Study Part 1: Questionnaire respondents (N = 41/100) used
      the RBR in several ways, and found it most helpful for assessing healthy child
      development, charting/recording the visits, managing time effectively, addressing
      parent concerns, identifying health problems, and identifying high risk
      situations. The RBR was seen to be least helpful as a tool for managing or for
      referring identified health problems. Study Part 2: Charts from a total of 1,378
      well-baby visits on 176 children were audited. Well-baby care provided by the 20
      FP/GPs who used the RBR compared to that by the 18 non-users was statistically
      more likely to include documentation of type of feeding (p = 0.023), discussion
      of safety issues (p < 0.001), assessment of development (p = 0.001), and overall
      comprehensiveness (p < 0.001). Well-baby care provided by the RBR users compared
      to that by the non-users was not more likely to include documentation of
      measurement of growth (p = 0.097), or physical examination (p = 0.828).
      CONCLUSION: The RBR was widely used by FP/GPs in these settings. RBR users found
      it helpful for many purposes, and had a consistently high rate of documentation
      of many aspects of well-baby care. The Rourke Baby Record has become a de facto
      gold standard clinical practice tool in knowledge translation for pediatric
      preventive medicine and health surveillance for primary care pediatric providers.

PMID- 19402913
TI  - Performance evaluation of inpatient service in Beijing: a horizontal comparison
      with risk adjustment based on Diagnosis Related Groups.
AB  - BACKGROUND: The medical performance evaluation, which provides a basis for
      rational decision-making, is an important part of medical service research.
      Current progress with health services reform in China is far from satisfactory,
      without sufficient regulation. To achieve better progress, an effective tool for
      evaluating medical performance needs to be established. In view of this, this
      study attempted to develop such a tool appropriate for the Chinese context.
      METHODS: Data was collected from the front pages of medical records (FPMR) of all
      large general public hospitals (21 hospitals) in the third and fourth quarter of
      2007. Locally developed Diagnosis Related Groups (DRGs) were introduced as a tool
      for risk adjustment and performance evaluation indicators were established:
      Charge Efficiency Index (CEI), Time Efficiency Index (TEI) and inpatient
      mortality of low-risk group cases (IMLRG), to reflect respectively work
      efficiency and medical service quality. Using these indicators, the inpatient
      services' performance was horizontally compared among hospitals. Case-mix Index
      (CMI) was used to adjust efficiency indices and then produce adjusted CEI (aCEI)
      and adjusted TEI (aTEI). Poisson distribution analysis was used to test the
      statistical significance of the IMLRG differences between different hospitals.
      RESULTS: Using the aCEI, aTEI and IMLRG scores for the 21 hospitals, Hospital A
      and C had relatively good overall performance because their medical charges were
      lower, LOS shorter and IMLRG smaller. The performance of Hospital P and Q was the
      worst due to their relatively high charge level, long LOS and high IMLRG. Various
      performance problems also existed in the other hospitals. CONCLUSION: It is
      possible to develop an accurate and easy to run performance evaluation system
      using Case-Mix as the tool for risk adjustment, choosing indicators close to
      consumers and managers, and utilizing routine report forms as the basic
      information source. To keep such a system running effectively, it is necessary to
      improve the reliability of clinical information and the risk-adjustment ability
      of Case-Mix.

PMID- 19402914
TI  - Development of an accurate classification system of proteins into structured and
      unstructured regions that uncovers novel structural domains: its application to
      human transcription factors.
AB  - BACKGROUND: In addition to structural domains, most eukaryotic proteins possess
      intrinsically disordered (ID) regions. Although ID regions often play important
      functional roles, their accurate identification is difficult. As human
      transcription factors (TFs) constitute a typical group of proteins with long ID
      regions, we regarded them as a model of all proteins and attempted to accurately
      classify TFs into structural domains and ID regions. Although an extremely high
      fraction of ID regions besides DNA binding and/or other domains was detected in
      human TFs in our previous investigation, 20% of the residues were left
      unassigned. In this report, we exploit the generally higher sequence divergence
      in ID regions than in structural regions to completely divide proteins into
      structural domains and ID regions. RESULTS: The new dichotomic system first
      identifies domains of known structures, followed by assignment of structural
      domains and ID regions with a combination of pre-existing tools and a newly
      developed program based on sequence divergence, taking un-aligned regions into
      consideration. The system was found to be highly accurate: its application to a
      set of proteins with experimentally verified ID regions had an error rate as low
      as 2%. Application of this system to human TFs (401 proteins) showed that 38% of
      the residues were in structural domains, while 62% were in ID regions. The
      preponderance of ID regions makes a sharp contrast to TFs of Escherichia coli
      (229 proteins), in which only 5% fell in ID regions. The method also revealed
      that 4.0% and 11.8% of the total length in human and E. coli TFs, respectively,
      are comprised of structural domains whose structures have not been determined.
      CONCLUSION: The present system verifies that sequence divergence including
      information of unaligned regions is a good indicator of ID regions. The system
      for the first time estimates the complete fractioning of structured/un-structured
      regions in human TFs, also revealing structural domains without homology to known
      structures. These predicted novel structural domains are good targets of
      structural genomics. When applied to other proteins, the system is expected to
      uncover more novel structural domains.

PMID- 19402915
TI  - Dietary fat intake and gestational weight gain in relation to estradiol and
      progesterone plasma levels during pregnancy: a longitudinal study in Swedish
      women.
AB  - BACKGROUND: Elevated pregnancy hormone levels, such as oestrogen and
      progesterone, may increase the risk of developing breast cancer both in mothers
      and offspring. However, the reasons for large inter-individual variations in
      estrogen and progesterone levels during pregnancy remain unknown. The objectives
      of this study were to investigate whether a) intakes of total dietary fat, types
      of fat (monounsaturated: MUFA, polyunsaturated: n-3 and n-6 PUFA, and saturated)
      and b) gestational weight gain are associated with estradiol and progesterone
      levels in plasma during pregnancy. METHODS: We measured body weight as well as
      estradiol and progesterone in plasma among 226 healthy pregnant Swedish women on
      gestation weeks 12, 25 and 33. At the same time points, dietary intake of total
      fat and types of fat (MUFA, PUFA, SFA, n-3 and n-6 PUFA) were estimated using 3
      day food diaries. RESULTS: A large variation in estradiol and progesterone levels
      was evident.Nulliparous women had 37%, 12% and 30% higher mean estradiol levels
      on gestation weeks 12, 25 and 33 compared to parous women (P = 0.008). No
      associations were found between dietary intake of total fat or fat subtypes
      (including n-3 PUFA and n-6 PUFA) and plasma estradiol or progesterone levels.
      Gestational weight gain was associated with progesterone levels (P = 0.03) but
      the effect was very small (20% increase in progesterone levels between
      gestational weeks 12 and 33 per kg body weight/week). CONCLUSION: No associations
      among gestational weight gain, maternal dietary fat intake (total or subtypes
      including n-3 PUFA and n-6 PUFA) and plasma estradiol levels were found. However,
      pregnancy progesterone levels correlated with weight gain during pregnancy.
      Identification of other possible determinants of pregnancy estradiol and
      progesterone levels, important for the development of breast cancer in both
      mothers and offspring, are needed.

PMID- 19402916
TI  - Learning a novel technique to identify possible melanomas: are Australian general
      practitioners better than their U.K. colleagues?
AB  - BACKGROUND: Spectrophotometric intracutaneous analysis (SIAscopy) is a
      multispectral imaging technique that is used to identify 'suspicious' (i.e.
      potentially malignant) pigmented skin lesions for further investigation. The
      MoleMate system is a hand-held scanner that captures SIAscopy images that are
      then classified by the clinician using a computerized diagnostic algorithm
      designed for the primary health care setting. The objectives of this study were
      to test the effectiveness of a computer program designed to train health care
      workers to identify the diagnostic features of SIAscopy images and compare the
      results of a group of Australian and a group of English general practitioners
      (GPs). METHODS: Thirty GPs recruited from the Perth (Western Australia)
      metropolitan area completed the training program at a workshop held in March
      2008. The accuracy and speed of their pre- and post-test scores were then
      compared with those of a group of 18 GPs (including 10 GP registrars) who
      completed a similar program at two workshops held in Cambridge (U.K.) in March
      and April, 2007. RESULTS: The median test score of the Australian GPs improved
      from 79.5% to 86.5% (median increase 5.5%; p < 0.001) while the median test score
      of the English GPs improved from 74.5% to 86.5% (median increase 9.5%; p <
      0.001). The Australian GPs had significantly higher pre-test scores but there
      were no significant differences in post-test scores between the Australian and
      English GPs or between the GPs and GP registrars. There was no significant
      difference in scores between GPs with previous dermoscopy experience or
      dermatology training. CONCLUSION: Most of the SIAscopy features can be learnt to
      a reasonable degree of accuracy with this brief computer training program.
      Although the Australian GPs scored higher in the pre-test, both groups had
      similar levels of accuracy and speed in interpreting the SIAscopy features after
      completing the program. Scores were not affected by previous dermoscopy
      experience or dermatology training, which suggests that the MoleMate system is
      relatively easy to learn.

PMID- 19402917
TI  - Comparison and prediction of pullout strength of conical and cylindrical pedicle
      screws within synthetic bone.
AB  - BACKGROUND: This study was designed to derive the theoretical formulae to predict
      the pullout strength of pedicle screws with an inconstant outer and/or inner
      diameter distribution (conical screws). For the transpedicular fixation, one of
      the failure modes is the screw loosening from the vertebral bone. Hence, various
      kinds of pedicle screws have been evaluated to measure the pullout strength using
      synthetic and cadaveric bone as specimens. In the literature, the Chapman's
      formula has been widely proposed to predict the pullout strength of screws with
      constant outer and inner diameters (cylindrical screws). METHODS: This study
      formulated the pullout strength of the conical and cylindrical screws as the
      functions of material, screw, and surgery factors. The predicted pullout strength
      of each screw was compared to the experimentally measured data. Synthetic bones
      were used to standardize the material properties of the specimen and provide
      observation of the loosening mechanism of the bone/screw construct. RESULTS: The
      predicted data from the new formulae were better correlated with the mean pullout
      strength of both the cylindrical and conical screws within an average error of
      5.0% and R2 = 0.93. On the other hand, the average error and R2 value of the
      literature formula were as high as -32.3% and -0.26, respectively. CONCLUSION:
      The pullout strength of the pedicle screws was the functions of bone strength,
      screw design, and pilot hole. The close correlation between the measured and
      predicted pullout strength validated the value of the new formulae, so as avoid
      repeating experimental tests.

PMID- 19402919
TI  - Why IQ is not a covariate in cognitive studies of neurodevelopmental disorders.
AB  - IQ scores are volatile indices of global functional outcome, the final common
      path of an individual's genes, biology, cognition, education, and experiences. In
      studying neurocognitive outcomes in children with neurodevelopmental disorders,
      it is commonly assumed that IQ can and should be partialed out of statistical
      relations or used as a covariate for specific measures of cognitive outcome. We
      propose that it is misguided and generally unjustified to attempt to control for
      IQ differences by matching procedures or, more commonly, by using IQ scores as
      covariates. We offer logical, statistical, and methodological arguments, with
      examples from three neurodevelopmental disorders (spina bifida meningomyelocele,
      learning disabilities, and attention deficit hyperactivity disorder) that: (1) a
      historical reification of general intelligence, g, as a causal construct that
      measures aptitude and potential rather than achievement and performance has
      fostered the idea that IQ has special status and that in studying neurocognitive
      function in neurodevelopmental disorders; (2) IQ does not meet the requirements
      for a covariate; and (3) using IQ as a matching variable or covariate has
      produced overcorrected, anomalous, and counterintuitive findings about
      neurocognitive function.

PMID- 19402920
TI  - Early prediction of long-term cognitive impairment after cardiac arrest.
AB  - This prospective study evaluated the prognostic value of early neurobiochemical
      markers, neuron-specific enolase and astroglial protein S-100B, for long-term
      cognitive outcome after cardiac arrest. Six months after admission of a cohort of
      80 consecutive patients, 26 survivors were able to undergo a neuropsychological
      test battery. Survivors showed low test performances in attention,
      learning/memory, and executive functioning. Neuropsychological bedside screening
      during the first month significantly differentiated between patients with and
      without long-term cognitive impairment. The neurobiochemical marker S-100B at day
      3 after admission was found to predict significant proportions of variance in
      specific cognitive domains (learning/memory and executive functioning). The
      results indicate that early neuropsychological assessment might help identify
      patients who run at risk of long-term neuropsychological dysfunction. This study
      also suggests that especially the protein S-100B provides valuable information on
      long-term cognitive outcomes. To understand the exact relationship, results have
      to be replicated in larger trials.

PMID- 19402918
TI  - The apoptotic machinery as a biological complex system: analysis of its omics and
      evolution, identification of candidate genes for fourteen major types of cancer,
      and experimental validation in CML and neuroblastoma.
AB  - BACKGROUND: Apoptosis is a critical biological phenomenon, executed under the
      guidance of the Apoptotic Machinery (AM), which allows the physiologic
      elimination of terminally differentiated, senescent or diseased cells. Because of
      its relevance to BioMedicine, we have sought to obtain a detailed
      characterization of AM Omics in Homo sapiens, namely its Genomics and Evolution,
      Transcriptomics, Proteomics, Interactomics, Oncogenomics, and Pharmacogenomics.
      METHODS: This project exploited the methodology commonly used in Computational
      Biology (i.e., mining of many omics databases of the web) as well as the High
      Throughput biomolecular analytical techniques. RESULTS: In Homo sapiens AM is
      comprised of 342 protein-encoding genes (possessing either anti- or pro-apoptotic
      activity, or a regulatory function) and 110 MIR-encoding genes targeting them:
      some have a critical role within the system (core AM nodes), others perform
      tissue-, pathway-, or disease-specific functions (peripheral AM nodes). By
      overlapping the cancer type-specific AM mutation map in the fourteen most
      frequent cancers in western societies (breast, colon, kidney, leukaemia, liver,
      lung, neuroblastoma, ovary, pancreas, prostate, skin, stomach, thyroid, and
      uterus) to their transcriptome, proteome and interactome in the same tumour type,
      we have identified the most prominent AM molecular alterations within each class.
      The comparison of the fourteen mutated AM networks (both protein- as MIR-based)
      has allowed us to pinpoint the hubs with a general and critical role in tumour
      development and, conversely, in cell physiology: in particular, we found that
      some of these had already been used as targets for pharmacological anticancer
      therapy. For a better understanding of the relationship between AM molecular
      alterations and pharmacological induction of apoptosis in cancer, we examined the
      expression of AM genes in K562 and SH-SY5Y after anticancer treatment.
      CONCLUSION: We believe that our data on the Apoptotic Machinery will lead to the
      identification of new cancer genes and to the discovery of new biomarkers, which
      could then be used to profile cancers for diagnostic purposes and to pinpoint new
      targets for pharmacological therapy. This approach could pave the way for future
      studies and applications in molecular and clinical Medicine with important
      perspectives both for Oncology as for Regenerative Medicine.

PMID- 19402922
TI  - Evidence for an attentional bias for washing- and checking-relevant stimuli in
      obsessive-compulsive disorder.
AB  - There is equivocal evidence whether or not patients with obsessive-compulsive
      disorder (OCD) share an attentional bias for concern-related material and if so,
      whether this reflects hypervigilance towards or problems to disengage from
      disorder-related material. In a recent study, we failed to detect an attentional
      bias in OCD patients using an emotional variant of the inhibition of return (IOR)
      paradigm containing OCD-relevant and neutral words. We reinvestigated the
      research question with a more stringent design that addressed potential
      moderators. A new IOR paradigm was set up using visual stimuli. Forty-two OCD
      patients and 31 healthy controls were presented with neutral (e.g., cup), anxiety
      relevant (e.g., shark), checking-relevant (e.g., broken door), and washing
      relevant (e.g., dirty toilet) cue pictures at one of two possible locations.
      Following a short or long interval sensitive to automatic versus controlled
      processes, a simple target stimulus appeared at either the cued or the uncued
      location. OCD patients responded significantly slower to targets that were
      preceded by an OCD-relevant cue. Results lend support to the claim that OCD
      patients share a processing abnormality for concern-related visual material.

PMID- 19402921
TI  - Rule violation errors are associated with right lateral prefrontal cortex atrophy
      in neurodegenerative disease.
AB  - Good cognitive performance requires adherence to rules specific to the task at
      hand. Patients with neurological disease often make rule violation (RV) errors,
      but the anatomical basis for RV during cognitive testing remains debated. The
      present study examined the neuroanatomical correlates of RV errors made on tests
      of executive functioning in 166 subjects diagnosed with neurodegenerative disease
      or as neurologically healthy. Specifically, RV errors were voxel-wisely
      correlated with gray matter volume derived from high-definition magnetic
      resonance images using voxel-based morphometry implemented in SPM2. Latent
      variable analysis showed that RV errors tapped a unitary construct separate from
      repetition errors. This analysis was used to generate factor scores to represent
      what is common among RV errors across tests. The extracted RV factor scores
      correlated with tissue loss in the lateral middle and inferior frontal gyri and
      the caudate nucleus bilaterally. When a more stringent control for global
      cognitive functioning was applied using Mini Mental State Exam scores, only the
      correlations with the right lateral prefrontal cortex (PFC) remained significant.
      These data underscore the importance of right lateral PFC in behavioral
      monitoring and highlight the potential of RV error assessment for identifying
      patients with damage to this region.

PMID- 19402923
TI  - Functional magnetic resonance imaging changes in amnestic and nonamnestic mild
      cognitive impairment during encoding and recognition tasks.
AB  - Functional magnetic resonance imaging (fMRI) shows changes in multiple regions in
      amnestic mild cognitive impairment (aMCI). The concept of MCI recently evolved to
      include nonamnestic syndromes, so little is known about fMRI changes in these
      individuals. This study investigated activation during visual complex scene
      encoding and recognition in 29 cognitively normal (CN) elderly, 19 individuals
      with aMCI, and 12 individuals with nonamnestic MCI (naMCI). During encoding, CN
      activated an extensive network that included bilateral occipital-parietal
      temporal cortex; precuneus; posterior cingulate; thalamus; insula; and medial,
      anterior, and lateral frontal regions. Amnestic MCI activated an anatomic subset
      of these regions. Non-amnestic MCI activated an even smaller anatomic subset.
      During recognition, CN activated the same regions observed during encoding except
      the precuneus. Both MCI groups again activated a subset of the regions activated
      by CN. During encoding, CN had greater activation than aMCI and naMCI in
      bilateral temporoparietal and frontal regions. During recognition, CN had greater
      activation than aMCI in predominantly temporoparietal regions bilaterally, while
      CN had greater activation than naMCI in larger areas involving bilateral
      temporoparietal and frontal regions. The diminished parietal and frontal
      activation in naMCI may reflect compromised ability to perform nonmemory (i.e.,
      attention/executive, visuospatial function) components of the task.

PMID- 19402924
TI  - Examination of processing speed deficits in multiple sclerosis using functional
      magnetic resonance imaging.
AB  - Although it is known that processing speed deficits are one of the primary
      cognitive impairments in multiple sclerosis (MS), the underlying neural
      mechanisms responsible for impaired processing speed remain undetermined. Using
      BOLD functional magnetic resonance imaging, the current study compared the brain
      activity of 16 individuals with MS to 17 healthy controls (HCs) during
      performance of a processing speed task, a modified version of the Symbol Digit
      Modalities Task. Although there were no differences in performance accuracy, the
      MS group was significantly slower than HCs. Although both groups showed similar
      activation involving the precentral gyrus and occipital cortex, the MS showed
      significantly less cerebral activity than HCs in bilateral frontal and parietal
      regions, similar to what has been reported in aging samples during speeded tasks.
      In the HC group, processing speed was mediated by frontal and parietal regions,
      as well as the cerebellum and thalamus. In the MS group, processing speed was
      mediated by insula, thalamus and anterior cingulate. It therefore appears that
      neural networks involved in processing speed differ between MS and HCs, and our
      findings are similar to what has been reported in aging, where damage to both
      white and gray matter is linked to processing speed impairments.

PMID- 19402925
TI  - Neurocognitive outcome after endoscopic third ventriculocisterostomy in patients
      with obstructive hydrocephalus.
AB  - Obstructive hydrocephalus can be treated with an extracranial shunting system or,
      when the obstruction is between the posterior third ventricle and the fourth
      ventricular outflow tracts, by an endoscopic third ventriculocisternostomy (ETV).
      The placement of an extracranial shunting device entails significant long-term
      risk of infection and malfunction. This risk has led to the concept that ETV is
      preferable to shunting. While the long-term cognitive performance of shunted
      hydrocephalus patients has been extensively examined, the outcome of patients
      undergoing ETV has been studied only sparsely. Ten adults who had undergone ETV
      were entered into the study under institutional review board approval. Each
      patient underwent a neuropsychological testing battery that included testing
      within the domains of basic attention, verbal memory, visual memory, language,
      and executive functioning. Aggregate test scores showed a decrease in performance
      in the domains of memory and executive functioning when compared to normative
      data. The present study revealed persistent cognitive inefficiencies in memory
      and executive domains in patients post-ETV intervention. A larger longitudinal
      study considering the impact of prior shunting, presence of headaches, emotional
      status, and surgical complications will assist in elucidating the etiology and
      eventual treatment of these deficits.

PMID- 19402927
TI  - Prospective memory in amnestic mild cognitive impairment.
AB  - Individuals with amnestic mild cognitive impairment (aMCI) often complain of
      difficulty remembering to carry out intended actions, consistent with findings of
      impaired prospective memory (PM) in this population. In this study, individuals
      with aMCI (N = 27) performed worse than healthy controls (N = 27) on the Memory
      for Intentions Screening Test (Raskin, 2004), including on time- and event-based
      subscales, and recognition of the intentions. The aMCI participants made more
      errors overall, but the proportion of the various error types did not differ
      between the two groups. Across all error types, both groups made more
      retrospective than prospective errors, especially on event-based PM tasks.
      Overall, the findings suggest that PM impairment in aMCI is associated with
      deficient cue detection involving both automatic (as in event-based tasks) and
      more strategic detection (as in time-based tasks) processes. These difficulties
      are likely due to a combination of problematic retrospective episodic memory
      (e.g., reduced encoding and/or consolidation of cue-intention pairings) and
      executive functions (e.g., decreased self-initiation, attention switching, and/or
      inhibition on memory tasks). Formal assessment of PM may help characterize the
      nature of the memory impairment among individuals with aMCI in clinical
      neuropsychological evaluations.

PMID- 19402926
TI  - Source memory and frontal functioning in Parkinson's disease.
AB  - The most extensively described pathological abnormality in Parkinson's disease
      (PD) is loss of dopaminergic neurons in the substantia nigra pars compacta and
      the ventral tegmental area, with degeneration of their striatal terminals.
      Because of the intimate connections between the striatum and the frontal lobes,
      individuals with PD often demonstrate impairments on those tasks relying on the
      prefrontal cortex (e.g., tests of executive functioning). Source memory, or
      memory for context, is believed to rely on the prefrontal cortex and has been
      previously associated with executive functioning performance, although it has
      received little attention in the PD literature. Executive functioning and source
      memory were measured in a group of nondemented PD patients and healthy control
      participants. Within the PD group, an anti-Parkinson's medication withdrawal
      manipulation was used to examine whether source memory was affected by phasic
      changes in dopamine levels. Compared to healthy control participants, PD patients
      were impaired in source memory (both on- and off-medication) and on a composite
      measure of executive functioning. Within the PD group, medication administration
      improved motor performance but did not have a significant effect on source
      memory.

PMID- 19402928
TI  - Partial measurement equivalence of French and English versions of the Canadian
      Study of Health and Aging neuropsychological battery.
AB  - Neuropsychological batteries are often translated for use across populations
      differing in preferred language. Yet, equivalence in construct measurement across
      groups cannot be assumed. To address this issue, we examined data from the
      Canadian Study of Health and Aging, a large study of older adults. We tested the
      hypothesis that the latent variables underlying the neuropsychological battery
      administered in French or English were the same (invariant). The best-fitting
      baseline model, established in the English-speaking Exploratory sample (n = 716),
      replicated well in the English-speaking Validation sample (n = 715), and the
      French-speaking sample (FS, n = 446). Across the English- and FSs, two of the
      factors, Long-term Retrieval and Visuospatial speed, displayed invariance, that
      is, reflected the same constructs measured in the same scales. In contrast, the
      Verbal Ability factor showed only partial invariance, reflecting differences in
      the relative difficulty of some tests of language functions. This empirical
      demonstration of partial measurement invariance lends support to the continued
      use of these translated measures in clinical and research contexts and
      illustrates a framework for detailed evaluation of the generality of models of
      cognition and psychopathology, across groups of any sort.

PMID- 19402930
TI  - Construct validity of the Trail Making Test: role of task-switching, working
      memory, inhibition/interference control, and visuomotor abilities.
AB  - The aim of this study was to clarify which cognitive mechanisms underlie Trail
      Making Test (TMT) direct and derived scores. A comprehensive review of the
      literature on the topic was carried out to clarify which cognitive factors had
      been related to TMT performance. Following the review, we explored the relative
      contribution from working memory, inhibition/interference control, task-switching
      ability, and visuomotor speed to TMT performance. Forty-one healthy old subjects
      participated in the study and performed a battery of neuropsychological tests
      including the TMT, the Digit Symbol subtest [Wechsler Adult Intelligence Scale
      (Third Version) (WAIS-III)], a Finger Tapping Test, the Digits Forward and
      Backward subtests (WAIS-III), Stroop Test, and a task-switching paradigm inspired
      in the Wisconsin Card Sorting Test. Correlation and regression analyses were used
      in order to clarify the joint and unique contributions from different cognitive
      factors to the prediction of TMT scores. The results suggest that TMT-A requires
      mainly visuoperceptual abilities, TMT-B reflects primarily working memory and
      secondarily task-switching ability, while B-A minimizes visuoperceptual and
      working memory demands, providing a relatively pure indicator of executive
      control abilities.

PMID- 19402929
TI  - Cognitive decline in Parkinson's disease: a prospective longitudinal study.
AB  - This controlled prospective study examined the evolution and predictors of
      cognitive decline in Parkinson's disease (PD). Consecutive patients diagnosed at
      baseline with PD (n = 89), established PD (EPD) patients (n = 52) with a mean
      disease duration of 6.5 years, and healthy control subjects (n = 64) underwent
      extensive neuropsychological assessment twice, approximately 3 years apart. A
      standardized regression-based method, normative data, and multivariate normative
      comparisons were used to assess the cognitive course of PD. Cognitive performance
      of newly diagnosed patients decreased significantly over time, particularly on
      measures of psychomotor speed and attention and to a lesser extent on tests of
      memory, visuospatial skills, and executive functions. About 50% of the patients
      showed cognitive decline and 9% developed dementia. Similar results were observed
      in EPD patients. None of the baseline features predicted cognitive change in
      newly diagnosed patients, whereas age at disease onset and axial impairment
      (postural and gait disorders) contributed to decline in established patients. We
      conclude that within few years after diagnosis, PD patients show faster rate of
      cognitive decline than matched healthy subjects, particularly in domains of
      attention and psychomotor speed. Selection bias probably led to underestimation
      of the true extent of cognitive decline in established patients.

PMID- 19402931
TI  - The impact of multiple sclerosis on patients' performance on the Stroop Test:
      processing speed versus interference.
AB  - Deficits in multiple sclerosis (MS) patients' performance on the Stroop Test have
      been attributed to problems with processing speed and selective attention. Data
      for 248 MS patients and 178 controls on all three trials of the Stroop were
      combined using various scoring formulas proposed for assessing processing speed,
      color difficulty, and interference. The greatest differences between patients and
      controls involved processing speed. Formulas purporting to measure interference
      yielded highly inconsistent results: Significant differences between groups were
      found on two of the most common measures but were in opposite directions. This
      contradiction stems from the failure of both measures to effectively control for
      processing speed when assessing interference. Three alternative measures, using
      relative, ratio, and residualized scores, offer much better indices of
      interference. When assessed with these alternative measures, interference
      increased with age, but no differences between patients and controls were found.
      Difficulties that MS patients have with the Stroop Test are confined to
      processing speed.

PMID- 19402933
TI  - Is "clinical" insight the same as "cognitive" insight in schizophrenia?
AB  - Poor insight is associated with impaired cognitive function in psychosis. Whether
      poor clinical insight overlaps with other aspects of self-awareness in
      schizophrenia, such as cognitive self-awareness, is unclear. We investigated
      whether awareness of clinical state ("clinical insight") and awareness of
      cognitive deficits ("cognitive insight") overlap in schizophrenia in a sample of
      51 stabilized patients with chronic schizophrenia. Cognitive insight was assessed
      in terms of the agreement between subjective self-report and neuropsychological
      assessment. Patients who show good cognitive insight did not necessarily show
      good clinical insight. By contrast, self-report and objective neuropsychological
      assessment only correlated for patients in the intact clinical insight group and
      not for those in the impairment clinical insight group. We conclude that while
      good cognitive insight may not be necessary for good clinical insight, good
      cognitive awareness is at least partly reliant on the processes involved in
      clinical insight.

PMID- 19402932
TI  - Neuropsychological patterns in magnetic resonance imaging-defined subgroups of
      patients with degenerative dementia.
AB  - We hypothesized that specific neuropsychological deficits were associated with
      specific patterns of atrophy. A magnetic resonance imaging volumetric study and a
      neuropsychological protocol were obtained for patients with several
      frontotemporal lobar dementia phenotypes including a social/dysexecutive
      (SOC/EXEC, n = 17), progressive nonfluent aphasia (n = 9), semantic dementia (n =
      7), corticobasal syndrome (n = 9), and Alzheimer's disease (n = 21). Blinded to
      testing results, patients were partitioned according to pattern of predominant
      cortical atrophy; our partitioning algorithm had been derived using seriation, a
      hierarchical classification technique. Neuropsychological test scores were
      regressed versus these atrophy patterns as fixed effects using the covariate
      total atrophy as marker for disease severity. The results showed the model
      accounted for substantial variance. Furthermore, the "large-scale networks"
      associated with each neuropsychological test conformed well to the known
      literature. For example, bilateral prefrontal cortical atrophy was exclusively
      associated with SOC/EXEC dysfunction. The neuropsychological principle of "double
      dissociation" was supported not just by such active associations but also by the
      "silence" of locations not previously implicated by the literature. We conclude
      that classifying patients with degenerative dementia by specific pattern of
      cortical atrophy has the potential to predict individual patterns of cognitive
      deficits.

PMID- 19402935
TI  - Discrepancies between balance confidence and physical performance among community
      dwelling Korean elders: a population-based study.
AB  - BACKGROUND: This study investigates discrepancies between the confidence
      expressed by Korean elders in their balance and their actual physical
      performances according to sex and age. It also attempts to identify the factors
      responsible for such gaps or discrepancies. METHODS: The Korean Longitudinal
      Study on Health and Aging (KLoSHA) was designed as a population-based prospective
      cohort study on the health and aging of Korean adults aged 65 years and over. We
      evaluated 1000 of 1118 randomly selected subjects in terms of activities-specific
      balance confidence (ABC) and performance in regard to balance and gait (POMA).
      Activities of daily living (ADL) and instrumental activities of daily living
      (IADL) were assessed to measure disability. Pain-related dysfunctions, depression
      and cognitive functions were assessed. Next, we assessed the relationship between
      balance confidence and physical performance and functioning by sex and age.
      RESULTS: The balance confidence of elderly women was lower than that of elderly
      men, although the physical performances of men and women under the age of 80 were
      similar. Women showed increased functional disability related to lower extremity
      pain and closely associated with balance confidence. However, psychological
      variables such as depression and cognitive functioning did not affect balance
      confidence. CONCLUSION: We found a discrepancy between balance confidence and
      physical performance according to sex and age among Koreans elders. Low balance
      confidence among women elders was correlated with pain-related dysfunctions other
      than those reflected in POMA scores. Therefore, enhancing confidence and
      controlling pain as a means of preventing disability should be emphasized when
      developing models for maintaining and promoting health in elders.

PMID- 19402934
TI  - Preliminary evidence for progressive prefrontal abnormalities in adolescents and
      young adults with bipolar disorder.
AB  - Previous cross-sectional study of ventral prefrontal cortex (VPFC) implicated
      progressive volume abnormalities during adolescence in bipolar disorder (BD). In
      the present study, a within-subject, longitudinal design was implemented to
      examine brain volume changes during adolescence/young adulthood. We hypothesized
      that VPFC volume decreases over time would be greater in adolescents/young adults
      with BD than in healthy comparison adolescents/young adults. Eighteen
      adolescents/young adults (10 with BD I and 8 healthy comparison participants)
      underwent two high-resolution magnetic resonance imaging scans over approximately
      2 years. Regional volume changes over time were measured. Adolescents/young
      adults with BD displayed significantly greater volume loss over time, compared to
      healthy comparison participants, in a region encompassing VPFC and rostral PFC
      and extending to rostral anterior cingulate cortex (p < .05). Additional areas
      where volume change differed between groups were observed. While data should be
      interpreted cautiously due to modest sample size, this study provides preliminary
      evidence to support the presence of accelerated loss in VPFC and rostral PFC
      volume in adolescents/young adults with BD.

PMID- 19402936
TI  - Dietary intakes of children with Crohn's disease.
AB  - Approximately 25 % of individuals with Crohn's disease (CD), a life-long
      relapsing-remitting disease, are diagnosed during childhood and adolescence.
      Symptoms of CD, including abdominal pain, nausea and diarrhoea, can lead to
      reduced food intake, which may negatively have an impact on nutritional status
      during this critical period of growth and development. The aims of the present
      study were to assess the growth and adequacy of dietary intakes of children with
      CD at Sydney Children's Hospital, Randwick, and compare with healthy controls.
      Sixty-three subjects aged 10-16 years were recruited, including: children with
      active CD (n 18), children with CD in remission (n 23) and healthy controls (n
      22). Dietary intake was assessed using a FFQ and compared with current Australian
      recommended dietary intakes (RDI). Growth and dietary intakes were compared
      between groups. Subjects with active CD had lower weight and BMI Z scores than
      children in remission and controls. The energy intakes of children with active CD
      and those in remission were significantly lower than estimated energy
      requirements (P = 0.001 and P = 0.03 respectively). Children with active CD did
      not meet the RDI for Fe and their Ca intake was lower than the RDI (P = 0.04). In
      conclusion, the dietary intake of children with active CD was impaired, with
      inadequate intakes of energy, Ca and Fe. Reduced energy intakes during active
      disease may contribute to poor weight gain and impaired growth. Quantifying
      nutrient intake and ascertaining requirements for nutritional supplementation are
      essential components of successful management in paediatric CD.

PMID- 19402937
TI  - Age dependence of plasma phospholipid fatty acid levels: potential role of
      linoleic acid in the age-associated increase in docosahexaenoic acid and
      eicosapentaenoic acid concentrations.
AB  - Limited information is available with respect to the association between age and
      the plasma phospholipid fatty acid profile. Therefore we investigated the
      association between plasma phospholipid fatty acid status and age after
      correction for sex, smoking, alcohol use, BMI and fish intake. Plasma
      phospholipid fatty acid composition was measured and information on fish intake
      and other potential covariates was collected in 234 participants of the
      Maastricht Aging Study. The participants were healthy individuals of both sexes
      with an age range between 36 and 88 years. Hierarchical linear regression
      analyses were applied to study the relationship between age and fatty acid
      concentrations. After correction for fish consumption and other relevant
      covariates, a significant positive relationship was observed between age of the
      subjects and their plasma phospholipid concentrations of DHA (22 : 6n-3, P =
      0.006) and EPA (20 : 5n-3; P = 0.001). Age contributed 2.3 and 3.9 % to the
      amount of explained variance, respectively. The higher n-3 long-chain PUFA status
      at advanced age was confirmed by lower concentrations of their putative 'shortage
      marker' Osbond acid (ObA, 22 : 5n-6; P = 0.022 for the relationship with age
      after correction for covariates and fish intake, R2 0.022). Concentrations of
      linoleic acid (LA; 18 : 2n-6) were negatively associated with age (P < 0.001; R2
      0.061). In conclusion, DHA and EPA concentrations appeared to be higher in older
      age groups, partly because of a higher fish intake and partly because of another
      age-associated mechanism, possibly involving the well-known competition with LA.

PMID- 19402938
TI  - Quercetin reduces systolic blood pressure and plasma oxidised low-density
      lipoprotein concentrations in overweight subjects with a high-cardiovascular
      disease risk phenotype: a double-blinded, placebo-controlled cross-over study.
AB  - Regular consumption of flavonoids may reduce the risk for CVD. However, the
      effects of individual flavonoids, for example, quercetin, remain unclear. The
      present study was undertaken to examine the effects of quercetin supplementation
      on blood pressure, lipid metabolism, markers of oxidative stress, inflammation,
      and body composition in an at-risk population of ninety-three overweight or obese
      subjects aged 25-65 years with metabolic syndrome traits. Subjects were
      randomised to receive 150 mg quercetin/d in a double-blinded, placebo-controlled
      cross-over trial with 6-week treatment periods separated by a 5-week washout
      period. Mean fasting plasma quercetin concentrations increased from 71 to 269
      nmol/l (P < 0.001) during quercetin treatment. In contrast to placebo, quercetin
      decreased systolic blood pressure (SBP) by 2.6 mmHg (P < 0.01) in the entire
      study group, by 2.9 mmHg (P < 0.01) in the subgroup of hypertensive subjects and
      by 3.7 mmHg (P < 0.001) in the subgroup of younger adults aged 25-50 years.
      Quercetin decreased serum HDL-cholesterol concentrations (P < 0.001), while total
      cholesterol, TAG and the LDL:HDL-cholesterol and TAG:HDL-cholesterol ratios were
      unaltered. Quercetin significantly decreased plasma concentrations of atherogenic
      oxidised LDL, but did not affect TNF-alpha and C-reactive protein when compared
      with placebo. Quercetin supplementation had no effects on nutritional status.
      Blood parameters of liver and kidney function, haematology and serum electrolytes
      did not reveal any adverse effects of quercetin. In conclusion, quercetin reduced
      SBP and plasma oxidised LDL concentrations in overweight subjects with a high-CVD
      risk phenotype. Our findings provide further evidence that quercetin may provide
      protection against CVD.

PMID- 19402939
TI  - The Toxoplasma gondii plastid replication and repair enzyme complex, PREX.
AB  - A plastid-like organelle, the apicoplast, is essential to the majority of
      medically and veterinary important apicomplexan protozoa including Toxoplasma
      gondii and Plasmodium. The apicoplast contains multiple copies of a 35 kb genome,
      the replication of which is dependent upon nuclear-encoded proteins that are
      imported into the organelle. In P. falciparum an unusual multi-functional gene,
      pfprex, was previously identified and inferred to encode a protein with DNA
      primase, DNA helicase and DNA polymerase activities. Herein, we report the
      presence of a prex orthologue in T. gondii. The protein is predicted to have a bi
      partite apicoplast targeting sequence similar to that demonstrated on the PfPREX
      polypeptide, capable of delivering marker proteins to the apicoplast. Unlike the
      P. falciparum gene that is devoid of introns, the T. gondii prex gene carries 19
      introns, which are spliced to produce a contiguous mRNA. Bacterial expression of
      the polymerase domain reveals the protein to be active. Consistent with the
      reported absence of a plastid in Cryptosporidium species, in silico analysis of
      their genomes failed to demonstrate an orthologue of prex. These studies indicate
      that prex is conserved across the plastid-bearing apicomplexans and may play an
      important role in the replication of the plastid genome.

PMID- 19402940
TI  - Morphological and molecular characterization of renal ciliates infecting farmed
      snails in Spain.
AB  - Renal infections by parasitic ciliates were studied in adult snails of Helix
      aspersa aspersa and Helix aspersa maxima collected from 2 mixed rearing system
      based heliciculture farms located in Galicia (NW Spain). The occurrence of
      ciliates was also examined in slugs (Deroceras reticulatum) invading the
      greenhouses where first growing and fattening of snails is carried out.
      Histological examinations revealed a severe destruction of the renal epithelium
      in heavily infected hosts. Three ciliate isolates, one from each host species,
      were obtained and grown in axenic cultures. Cultured and parasitic ciliates were
      characterized morphologically and morphometrically. In addition, the encystment
      behaviour, the occurrence of autogamy, and the sequences of the mitochondrial
      cytochrome-c oxidase subunit 1 (cox1) and the small subunit ribosomal RNA (SSU
      rRNA) genes were also studied in the 3 isolates. A polymorphic life cycle
      involving resting and reproductive cysts, together with the morphological and
      morphometrical characteristics and the confirmation that autogamy occurs within
      cysts, demonstrate that our ciliates belong to the species Tetrahymena rostrata
      (Kahl, 1926) Corliss, 1952. The 3 isolates formed a well-supported clade using
      both genetic markers, and were clearly separate from the strain ATCC(R) 30770,
      which has been identified as Tetrahymena rostrata. We argue that our Spanish
      isolates should be regarded as Tetrahymena rostrata, and that the ATCC isolate
      should be regarded as a misidentification as neither cytological nor
      cytogenetical support for its identity has been presented.

PMID- 19402941
TI  - Stage-specific expression of Nc SAG4 as a marker of chronic Neospora caninum
      infection in a mouse model.
AB  - Neospora caninum infection persists throughout the life of its intermediate host
      due to the conversion of tachyzoites to slowly dividing bradyzoites that encyst
      in the brain. This event results in persistent N. caninum infection in bovine
      herds and partially explains the poor efficacy of many chemotherapeutic agents
      and vaccine formulations. Thus, there is a need for greater understanding of the
      tachyzoite-to-bradyzoite conversion mechanisms. Here we studied for the first
      time the transcription kinetics of the N. caninum bradyzoite-specific gene NcSAG4
      in brain samples from chronically infected mice by means of real-time RT-PCR.
      NcSAG4-messenger RNA (mRNA) levels increased significantly during the chronic
      phase but followed 2 different expression patterns depending on the isolate used
      for murine inoculation. NcSAG4-mRNA levels in brains from Nc-1-inoculated mice
      peaked during late chronic infection (on day 64 post-infection, p.i.), whereas
      those from Nc-Liv-inoculated mice peaked earlier during the chronic infection (on
      day 32 p.i.). This difference could be a reflection of the different abilities of
      these isolates to replicate and form cysts in parasitized brains. These results
      are consistent with our observations of anti-rNcSAG4 antibody production; low
      levels were present at seroconversion and slowly increased during the chronic
      phase. In contrast, NcSAG1 transcription levels, which mark the tachyzoite stage,
      were maintained without variation in both groups of mice. This suggests the
      presence of a significant amount of tachyzoites or intermediate zoites expressing
      NcSAG1 in the brain, even during the late chronic infection.

PMID- 19402942
TI  - Hatching behaviour of Nematodirus filicollis in a flock co-infected with
      Nematodirus battus.
AB  - The development and survival of larvae of Nematodirus filicollis, an important
      nematode parasite of ruminants, were extensively investigated in the laboratory
      for the first time, using eggs harvested from sheep grazing in the UK in winter.
      Third-stage larvae (L3s) developed within the eggs between 12 and 25 degrees C,
      with the proportion of eggs developing successfully being highest at the upper
      end of this range. Eggs required chilling below 10 degrees C before being able to
      hatch at all, and maximum hatch was observed only following chilling to 4 degrees
      C. Hatching occurred above 6 degrees C, and peaked at 13 degrees C, with the
      proportion of eggs hatching decreasing to 17-20 degrees C, which appears to form
      an upper threshold temperature for hatching. When fully developed eggs were
      placed at 11-13 degrees C, L3 emerged very rapidly with hatching being completed
      within 6 days. Mortality of emerged L3s increased with temperature, particularly
      above 20 degrees C. For this parasite, given the low minimum hatching thresholds
      and the rapid emergence of L3, the existence of an upper hatching threshold is
      likely to have limited impact on patterns of larval availability on pasture. The
      strict requirement for chilling is surprising, being at odds with both previous
      observations and the wide geographical distribution of this species. It is
      possible that the proportion of eggs requiring chilling is an adaptable trait,
      enabling early infection of naive hosts in the face of competition from N.
      battus, yet also persistence in regions that do not provide good conditions for
      the chilling of eggs. Further study of selectable variation in this trait could
      help us to understand the contrasting geographical ranges and disease patterns
      within the genus, and how different species might respond to climate change.

PMID- 19402943
TI  - A corner store intervention in a low-income urban community is associated with
      increased availability and sales of some healthy foods.
AB  - OBJECTIVE: While corner store-based nutrition interventions have emerged as a
      potential strategy to increase healthy food availability in low-income
      communities, few evaluation studies exist. We present the results of a trial in
      Baltimore City to increase the availability and sales of healthier food options
      in local stores. DESIGN: Quasi-experimental study. SETTING: Corner stores owned
      by Korean-Americans and supermarkets located in East and West Baltimore.
      SUBJECTS: Seven corner stores and two supermarkets in East Baltimore received a
      10-month intervention and six corner stores and two supermarkets in West
      Baltimore served as comparison. RESULTS: During and post-intervention, stocking
      of healthy foods and weekly reported sales of some promoted foods increased
      significantly in intervention stores compared with comparison stores. Also,
      intervention storeowners showed significantly higher self-efficacy for stocking
      some healthy foods in comparison to West Baltimore storeowners. CONCLUSIONS:
      Findings of the study demonstrated that increases in the stocking and promotion
      of healthy foods can result in increased sales. Working in small corner stores
      may be a feasible means of improving the availability of healthy foods and their
      sales in a low-income urban community.

PMID- 19402944
TI  - Food and nutrient intakes of 9-month-old infants in Adelaide, Australia.
AB  - OBJECTIVE: To describe the food and nutrient intakes of 9-month-old infants.
      DESIGN: A survey undertaken as part of a longitudinal study of child growth and
      development. Infant diet was characterised through a structured interview in
      which consumption frequency and portion size of foods were obtained. This method
      was compared with a 4 d diary and had adequate relative validity. SETTING:
      Adelaide, Australia. SUBJECTS: Three hundred and forty-one infants for whom
      dietary data were plausible according to pre-specified criteria. RESULTS: At 9
      months of age, the median body weights for 161 girls and 180 boys were 8.8 and
      9.6 kg, respectively. Differences in intakes between boys and girls largely
      reflected differences in size. Median daily energy intake was 3541 kJ and median
      contributions of protein, fat and carbohydrate to total energy were 13 %, 36 %
      and 50 %. Using published Estimated Average Requirements, Zn intake was
      inadequate for <1 % of children not breast-fed at this age while Fe intake was
      inadequate for 9 %. Infants who were still breast-fed (35 %) had more diversity
      in the foods that provided additional energy, compared with those not receiving
      breast milk, and were less likely to consume nutrient-displacing drinks such as
      juice or cordial. Cow's milk was the main drink for 5 % of infants. CONCLUSIONS:
      In a group of Australian-born children, an important proportion had weaning diets
      that were low in Fe. Fat intake of many children was below current
      recommendations and cow's milk was the main milk source for a small minority.

PMID- 19402945
TI  - Sugar and total energy content of household food purchases in Brazil.
AB  - OBJECTIVE: To study the role of energy derived from sugar (both table sugar and
      sugar added to processed foods) in the total energy content of food purchases in
      Brazil. DESIGN: Food purchase data were collected during a national household
      budget survey carried out between June 2002 and July 2003 on a probabilistic
      sample representative of all households in the country. The amount of food
      purchased in this 12-month period was transformed into energy and energy from
      sugar using food composition tables. Multiple linear regression models were used
      to study the association between amount of energy from sugar and total energy
      content of food purchases, controlling for sociodemographic variables and
      potential interactions between these variables and sugar purchases. RESULTS:
      There was a positive and significant association between energy from sugar and
      total household energy purchases. A 1 kJ increase in sugar purchase corresponded
      to a 3.637 kJ increase in total energy. In the absence of expenditure on meals
      outside the home, i.e. when household food purchases tend to approximate actual
      food consumption by household members, sugar purchase of 1926.35 kJ/d (the 90th
      percentile of the distribution of sugar purchases in Brazil) was associated,
      depending on income strata, with total energy purchase over 40-60 % of the
      recommended daily value for energy intake in Brazil. CONCLUSIONS: The present
      results corroborate the recommendations of the WHO and the Brazilian Ministry of
      Health regarding limiting the consumption of sugar.

PMID- 19402946
TI  - Association between educational level and vegetable use in nine European
      countries.
AB  - OBJECTIVE: The relationship of socio-economic status and vegetable consumption is
      examined in nine European countries. The aim is to analyse whether the pattern of
      socio-economic variation with regard to vegetable consumption is similar in all
      studied countries with high v. low vegetable availability and affordability, and
      whether education has an independent effect on vegetable consumption once the
      effects of other socio-economic factors have been taken into account. DESIGN: The
      data for the study were obtained from national surveys conducted in Finland,
      Denmark, Germany, Estonia, Latvia, Lithuania, France, Italy and Spain, in 1998 or
      later. These surveys included data on the frequency of use of vegetables. Food
      Balance Sheets indicated that the availability of vegetables was best in the
      Mediterranean countries. The prices of vegetables were lowest in the
      Mediterranean countries and Germany. RESULTS: Educational level was positively
      associated with vegetable consumption in the Nordic and Baltic countries. In the
      Mediterranean countries, education was not directly associated with the use of
      vegetables but, after adjusting for place of residence and occupation, it was
      found that those with a lower educational level consumed vegetables slightly more
      often. Manual workers consumed vegetables less often than non-manual workers, but
      otherwise there was no systematic association with occupation. CONCLUSIONS: The
      Mediterranean countries did not show a positive association between educational
      level and vegetable consumption. The positive association found in the Northern
      European countries is linked to the lower availability and affordability of
      vegetables there and their everyday cooking habits with no long-standing cultural
      tradition of using vegetables.

PMID- 19402947
TI  - Rapid assessment of infant feeding support to HIV-positive women accessing
      prevention of mother-to-child transmission services in Kenya, Malawi and Zambia.
AB  - OBJECTIVE: The possibility of mother-to-child transmission (MTCT) of HIV through
      breast-feeding has focused attention on how best to support optimal feeding
      practices especially in low-resource and high-HIV settings, which characterizes
      most of sub-Saharan Africa. To identify strategic opportunities to minimize late
      postnatal HIV transmission, we undertook a review of selected country experiences
      on HIV and infant feeding, with the aims of documenting progress over the last
      few years and determining the main challenges and constraints. DESIGN: Field
      teams conducted national-level interviews with key informants and visited a total
      of thirty-six facilities in twenty-one sites across the three countries--eighteen
      facilities in Malawi, eleven in Kenya and seven in Zambia. During these visits
      interviews were undertaken with key informants such as the district and facility
      management teams, programme coordinators and health workers. SETTING: A rapid
      assessment of HIV and infant feeding counselling in Kenya, Malawi and Zambia,
      undertaken from February to May 2007. RESULTS: Infant feeding counselling has,
      until now, been given low priority within programmes aimed at prevention of MTCT
      (PMTCT) of HIV. This is manifest in the lack of resources - human, financial and
      time--for infant feeding counselling, leading to widespread misunderstanding of
      the HIV transmission risks from breast-feeding. It has also resulted in lack of
      space and time for proper counselling, poor support and supervision, and very
      weak monitoring and evaluation of infant feeding. Finally, there are very few
      examples of linkages with community-based infant feeding interventions. However,
      all three countries have started to revise their feeding policies and strategies
      and there are signs of increased resources. CONCLUSIONS: In order to sustain this
      momentum it will be necessary to continue the advocacy with the HIV community and
      stress the importance of child survival--not just minimization of HIV
      transmission - and hence the need for integrating MTCT prevention.

PMID- 19402948
TI  - Nutritional status and dietary adequacy in rural communities of a protected area
      in Gabon.
AB  - OBJECTIVE: As part of a larger study designed to understand how to protect the
      food and nutrition security of individuals living in a protected area of Gabon,
      we assessed their nutritional status and its relationship to dietary adequacy and
      health status. DESIGN: A 7 d food consumption survey was conducted during each of
      the two major seasons using a weighing method. Data were also collected on
      weight, height and health of individuals as well as on sociodemographic
      characteristics and potential determinants of the nutrition situation. SETTING:
      Four rural communities were intentionally selected to represent both inland and
      coastal settings and access to food markets. SUBJECTS: Approximately 500
      individuals representing over 90% of the population of these communities
      participated in the survey during each season. RESULTS: Undernutrition was
      present in the area, particularly among children <5 years of age and the elderly.
      Health was generally good and under-fives were most frequently ill. Energy, Fe
      and vitamin A requirements of individuals were generally not satisfied; the
      opposite was true for protein. The estimated prevalence of inadequate intakes of
      energy and vitamin A was very high in most age groups. Global nutrient adequacy
      was associated with nutritional outcome. CONCLUSIONS: Individuals do not eat
      enough and breast-feeding practices are poor. Many suffer from undernutrition,
      particularly young children and the elderly. The results confirm the need to
      investigate the determinants of this poor nutrition situation to ensure that
      protection of natural resources will not be associated with harm to the well
      being of the population.

PMID- 19402949
TI  - Isolation and characterization of viable Toxoplasma gondii isolates revealed
      possible high frequency of mixed infection in feral cats ( Felis domesticus) from
      St Kitts, West Indies.
AB  - Cats are essential in the epidemiology of Toxoplasma gondii because they are the
      only hosts that can excrete the environmentally resistant oocysts in nature.
      Samples of serum, feces, and tissues from feral cats from St Kitts, West Indies
      were examined for T. gondii infection. Antibodies to T. gondii were assayed by
      the modified agglutination test, and found in 71 of 96 (73.9%) of cats with
      titres of 1:10 in six, 1: 20 in six,1:40 in seven,1: 80 in three, 1: 160 in 10,
      1:320 in 13, 1:640 in nine, and 1:1,280 or higher in 17. Tissues of 10 cats were
      bio-assayed in mice. Toxoplasma gondii was isolated from tissues of 7 cats; from
      hearts of 6, from tongue of 5, and brains of 3 cats. All 7 isolates were
      avirulent for mice. Toxoplasma gondii oocysts were not found in the feces of 51
      cats. Genotyping of these 7 T. gondii isolates by 10 multi-locus PCR-RFLP
      markers, including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and an
      apicoplast marker, Apico, revealed 4 genotypes, including clonal Type II, Type
      III and 2 unique genotypes. Five of the 7 cats had infection with 2 genotypes,
      indicating high frequency of mixed infection in the cat population on the St
      Kitts island.

PMID- 19402950
TI  - Temporal perspective and parental intention to accept the human papillomavirus
      vaccination for their daughter.
AB  - OBJECTIVE: A school-based vaccination programme to prevent infection with the
      human papillomavirus (HPV), the virus that causes cervical cancer, began in
      October 2008 in England. The present study evaluated the role of temporal
      perspective in the formation of attitudes and intentions towards the vaccine.
      DESIGN: A cross-sectional correlational survey of 245 parents of 11-12-year-old
      girls. METHODS: Parents read a passage about the HPV vaccine containing
      information about benefits and concerns parents might have about the vaccine.
      They then completed a thought listing task and measures of attitude, vaccine
      efficacy, anticipated regret, intention, and consideration of future
      consequences. RESULTS: Parents with higher consideration of future consequences
      generated more positive relative to negative thoughts, held more positive
      attitudes, higher response efficacy, reported higher anticipated regret about not
      vaccinating their daughters and held more positive intentions. Mediation analyses
      suggested that the influence of thoughts generated on intention to vaccinate was
      partially mediated by attitude, perceived vaccine efficacy, and anticipated
      regret if the vaccine were not taken up. CONCLUSION: Messages emphasizing
      efficacy of vaccination and anticipated regret are likely to promote vaccination
      uptake.

PMID- 19402951
TI  - ERK1/2 activation in reactive astrocytes of mice with pilocarpine-induced status
      epilepticus.
AB  - OBJECTIVE: To investigate the activation pattern of extracellular signal
      regulated kinase 1/2 (ERK1/2) in the hippocampus of mice during pilocarpine
      induced status epilepticus (SE) and its relationship with reactive astrogliosis.
      METHODS: Status epilepticus (SE) models were established by intraperitoneal
      injection of pilocarpine. The intervention group received the ERK1/2 signaling
      pathway inhibitor SL327 before the pilocarpine injection. We evaluated the SE
      model group, the intervention group and the control saline-treated group, at 6
      hours and 3 days after initiation of the seizure. Phosphorylated activated ERK1/2
      and glial fibrillary acidic protein (GFAP) were labeled with both single-labeling
      and sequential single-labeling immunohistochemical techniques. RESULTS: Among the
      pilocarpine-treated (SE model) mice, strong immunohistochemical staining of
      phospho-ERK1/2 was observed in the neurons and astrocytes of the hippocampus at 6
      hours after initiation of SE, whereas staining on the third day of SE was not
      different from the control saline-treated mice. In the SL327-treated mice
      (intervention group), SL327 effectively blocked the ERK1/2 activation and little
      gliosis could be detected at 6 hours and 3 days after initiation of SE; the
      levels of phospho-ERK1/2 remained low, but the level of gliosis was similar to
      that of SE mice. CONCLUSION: The ERK1/2 signaling pathway plays an important role
      in the early stage of reactive astrogliosis in mice with pilocarpine-induced SE.

PMID- 19402952
TI  - Virtual ventriculostomy with 'shifted ventricle': neurosurgery resident surgical
      skill assessment using a high-fidelity haptic/graphic virtual reality simulator.
AB  - Based on a study of 48 neurological residents using a high fidelity
      haptic/graphic virtual reality simulator to perform ventricular cannulation, we
      recorded absolute Euclidean distance from the catheter tip to the foramen of
      Monroe within the ventricle. The data suggest that as expected, successful first
      attempts to cannulate the virtual 'shifted ventricle' are much less frequent than
      previous assessments with normal virtual ventricular anatomy. Furthermore, the
      significant improvement observed by the second attempt implies that the learning
      curve has been affected and the process 'jump started'.

PMID- 19402953
TI  - Use of unstructured event-based reports for global infectious disease
      surveillance.
AB  - Free or low-cost sources of unstructured information, such as Internet news and
      online discussion sites, provide detailed local and near real-time data on
      disease outbreaks, even in countries that lack traditional public health
      surveillance. To improve public health surveillance and, ultimately,
      interventions, we examined 3 primary systems that process event-based outbreak
      information: Global Public Health Intelligence Network, HealthMap, and EpiSPIDER.
      Despite similarities among them, these systems are highly complementary because
      they monitor different data types, rely on varying levels of automation and human
      analysis, and distribute distinct information. Future development should focus on
      linking these systems more closely to public health practitioners in the field
      and establishing collaborative networks for alert verification and dissemination.
      Such development would further establish event-based monitoring as an invaluable
      public health resource that provides critical context and an alternative to
      traditional indicator-based outbreak reporting.

PMID- 19402954
TI  - Chronic wasting disease prions in elk antler velvet.
AB  - Chronic wasting disease (CWD) is a contagious, fatal prion disease of deer and
      elk that continues to emerge in new locations. To explore the means by which
      prions are transmitted with high efficiency among cervids, we examined prion
      infectivity in the apical skin layer covering the growing antler (antler velvet)
      by using CWD-susceptible transgenic mice and protein misfolding cyclic
      amplification. Our finding of prions in antler velvet of CWD-affected elk
      suggests that this tissue may play a role in disease transmission among cervids.
      Humans who consume antler velvet as a nutritional supplement are at risk for
      exposure to prions. The fact that CWD prion incubation times in transgenic mice
      expressing elk prion protein are consistently more rapid raises the possibility
      that residue 226, the sole primary structural difference between deer and elk
      prion protein, may be a major determinant of CWD pathogenesis.

PMID- 19402955
TI  - Virulent strain of hepatitis E virus genotype 3, Japan.
AB  - Hepatitis E virus (HEV) genotype 3, which usually causes asymptomatic infection
      in Japan, induced severe hepatitis in 8 patients. To better understand genetic
      features of HEV associated with increased virulence, we determined the complete
      or near-complete nucleotide sequences of HEV from these 8 patients and from 5
      swine infected with genotype 3 strain swJ19. Phylogenetic analysis showed that
      the isolates from the 8 patients and the 5 swine grouped separately from the
      other genotype 3 isolates to create a unique cluster, designated JIO. The human
      JIO-related viruses encoded 18 amino acids different from those of the other HEV
      genotype 3 strains. One substitution common to almost all human HEV strains in
      the JIO cluster was located in the helicase domain (V239A) and may be associated
      with increased virulence. A zoonotic origin of JIO-related viruses is suspected
      because the isolates from the 5 swine also possessed the signature V239A
      substitution in helicase.

PMID- 19402956
TI  - A case-control study on the origin of atypical scrapie in sheep, France.
AB  - A matched case-control study (95 cases and 220 controls) was designed to study
      risk factors for atypical scrapie in sheep in France. We analyzed contacts with
      animals from other flocks, lambing and feeding practices, and exposure to toxic
      substances. Data on the prnp genotype were collected for some case and control
      animals and included in a complementary analysis. Sheep dairy farms had a higher
      risk for scrapie (odds ratio [OR] 15.1, 95% confidence interval [CI] 3.3-69.7).
      Lower risk was associated with organic farms (OR 0.15, 95% CI 0.02-1.26), feeding
      corn silage (OR 0.16, 95% CI 0.05-0.53), and feeding vitamin and mineral
      supplements (OR 0.6, 95% CI 0.32-1.14). Genetic effects were quantitatively
      important but only marginally changed estimates of other variables. We did not
      find any risk factor associated with an infectious origin of scrapie. Atypical
      scrapie could be a spontaneous disease influenced by genetic and metabolic
      factors.

PMID- 19402957
TI  - New respiratory enterovirus and recombinant rhinoviruses among circulating
      picornaviruses.
AB  - Rhinoviruses and enteroviruses are leading causes of respiratory infections. To
      evaluate genotypic diversity and identify forces shaping picornavirus evolution,
      we screened persons with respiratory illnesses by using rhinovirus-specific or
      generic real-time PCR assays. We then sequenced the 5 untranslated region, capsid
      protein VP1, and protease precursor 3CD regions of virus-positive samples.
      Subsequent phylogenetic analysis identified the large genotypic diversity of
      rhinoviruses circulating in humans. We identified and completed the genome
      sequence of a new enterovirus genotype associated with respiratory symptoms and
      acute otitis media, confirming the close relationship between rhinoviruses and
      enteroviruses and the need to detect both viruses in respiratory specimens.
      Finally, we identified recombinants among circulating rhinoviruses and mapped
      their recombination sites, thereby demonstrating that rhinoviruses can recombine
      in their natural host. This study clarifies the diversity and explains the
      reasons for evolution of these viruses.

PMID- 19402958
TI  - Cross-border dissemination of methicillin-resistant Staphylococcus aureus,
      Euregio Meuse-Rhin region.
AB  - Because the prevalence of methicillin-resistant Staphylococcus aureus (MRSA)
      differs among the 3 countries forming the Euregio Meuse-Rhin (EMR) region
      (Belgium, Germany, and the Netherlands), cross-border healthcare requires
      information about the spread of MRSA in the EMR. We investigated the emergence,
      dissemination, and diversity of MRSA clones in the EMR by using several typing
      methods. MRSA associated with clonal complexes 5, 8, 30, and 45 was disseminated
      throughout the EMR. Dutch isolates, mainly associated with sequence types (ST)
      ST5-MRSA-II, ST5-MRSA-IV, ST8-MRSA-IV, and ST45-MSRA-IV had a more diverse
      genetic background than the isolates from Belgium and Germany, associated with
      ST45-MRSA-IV and ST5-MRSA-II, respectively. MRSA associated with pigs (ST398-MRSA
      IV/V) was found in the Dutch area of the EMR. Five percent of the MRSA isolates
      harbored Panton-Valentine leukocidin and were classified as community-associated
      MRSA associated with ST1, 8, 30, 80, and 89.

PMID- 19402959
TI  - Chloroquine-resistant haplotype Plasmodium falciparum parasites, Haiti.
AB  - Plasmodium falciparum parasites have been endemic to Haiti for >40 years without
      evidence of chloroquine (CQ) resistance. In 2006 and 2007, we obtained blood
      smears for rapid diagnostic tests (RDTs) and filter paper blots of blood from 821
      persons by passive and active case detection. P. falciparum infections diagnosed
      for 79 persons by blood smear or RDT were confirmed by PCR for the small subunit
      rRNA gene of P. falciparum. Amplification of the P. falciparum CQ resistance
      transporter (pfcrt) gene yielded 10 samples with amplicons resistant to cleavage
      by ApoI. A total of 5 of 9 samples had threonine at position 76 of pfcrt, which
      is consistent with CQ resistance (haplotypes at positions 72-76 were CVIET [n =
      4] and CVMNT [n = 1]); 4 had only the wild-type haplotype associated with CQ
      susceptibility (CVMNK). These results indicate that CQ-resistant haplotype P.
      falciparum malaria parasites are present in Haiti.

PMID- 19402960
TI  - CTX-M beta-lactamases in Escherichia coli from community-acquired urinary tract
      infections, Cambodia.
AB  - Despite the recent global spread of CTX-M beta-lactamases in Escherichia coli
      isolates from community-acquired urinary tract infections (CA-UTIs), their
      dissemination has been little studied in developing countries. In a 2-year
      prospective study, we documented the prevalence of extended-spectrum beta
      lactamases (ESBLs) in E. coli that were responsible for CA-UTIs in Phnom-Penh,
      Cambodia. Ninety-three E. coli strains were included. We observed a high
      prevalence of resistance to amoxicillin (88.2% of strains), cotrimoxazole
      (75.3%), ciprofloxacin (67.7%), gentamicin (42.5%), and third-generation
      cephalosporins (37.7%). A total of 34 strains carried ESBLs, all of which were
      CTX-M type. CTX-M carriage was associated with resistance to fluoroquinolones and
      aminoglycosides. U using repetitive extragenic palindromic-PCR, we identified 4
      clusters containing 9, 8, 3, and 2 strains. The prevalence of CTX-M beta
      lactamases has reached a critical level in Cambodia, which highlights the need
      for study of their spread in developing countries.

PMID- 19402962
TI  - Seroprevalence of antibodies to avian influenza virus A (H5N1) among residents of
      villages with human cases, Thailand, 2005.
AB  - In 2005, we assessed the seroprevalence of neutralizing antibodies to avian
      influenza virus A (H5N1) among 901 residents of 4 villages in Thailand where at
      least 1 confirmed human case of influenza (H5N1) had occurred during 2004.
      Although 68.1% of survey participants (median age 40 years) were exposed to
      backyard poultry and 25.7% were exposed to sick or dead chickens, all
      participants were seronegative for influenza virus (H5N1).

PMID- 19402961
TI  - Increased risk for severe malaria in HIV-1-infected adults, Zambia.
AB  - To determine whether HIV-1 infection and HIV-1-related immunosuppression were
      risk factors for severe malaria in adults with some immunity to malaria, we
      conducted a case-control study in Luanshya, Zambia, during December 2005-March
      2007. For each case-patient with severe malaria, we selected 2 matched controls
      (an adult with uncomplicated malaria and an adult without signs of disease). HIV
      1 infection was present in 93% of case-patients, in 52% of controls with
      uncomplicated malaria, and in 45% of asymptomatic controls. HIV-1 infection was a
      highly significant risk factor for adults with severe malaria compared with
      controls with uncomplicated malaria (odds ratio [OR] 12.6, 95% confidence
      interval [CI] 2.0-78.8, p = 0.0005) and asymptomatic controls (OR 16.6, 95% CI
      2.5-111.5, p = 0.0005). Persons with severe malaria were more likely to have a
      CD4 count <350/microL than were asymptomatic controls (OR 23.0, 95% CI 3.35
      158.00, p<0.0001).

PMID- 19402963
TI  - Hospitalizations and deaths associated with Clostridium difficile infection,
      Finland, 1996-2004.
AB  - To determine whether the rate of Clostridium difficile-associated disease (CDAD)
      and CDAD-related deaths were increasing in Finland, we analyzed registry data
      from 1996 through 2004. We determined the number of hospital discharges that had
      a diagnosis code specific for CDAD from the International Classification of
      Diseases, 10th revision: "enterocolitis due to Clostridium difficile" (A04.7) and
      "pseudomembranous enterocolitis associated with antimicrobial therapy" (K52.8),
      listed as any diagnosis in the National Hospital Discharge Registry. CDAD-related
      deaths were identified from death certificates. Those discharged with a CDAD
      diagnosis doubled from 810 (16/100,000 population) in 1996 to 1,787 (34/100,000)
      in 2004. The increase was most prominent for patients 7gt;64 years of age but
      concerned only those discharged with diagnosis code A04.7. The number of those
      discharged with diagnosis code K52.8 remained stable. The age-standardized
      mortality rate associated with CDAD increased from 9/million in 1998 to
      17/million in 2004; the increase was limited to persons 7gt;64 years of age.

PMID- 19402964
TI  - Methicillin-Resistant Staphylococcus aureus ST398 from human patients, upper
      Austria.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) clonal type ST398 is usually
      associated with animals. We examined 1,098 confirmed MRSA samples from human
      patients and found that 21 were MRSA ST398. Most (16) patients were farmers.
      Increasing prevalence from 1.3% (2006) to 2.5% (2008) shows emergence of MRSA
      ST398 in humans in Austria.

PMID- 19402966
TI  - Human Streptococcus agalactiae isolate in Nile tilapia (Oreochromis niloticus).
AB  - Streptococcus agalactiae, the Lancefield group B streptococcus (GBS) long
      recognized as a mammalian pathogen, is an emerging concern with regard to fish.
      We show that a GBS serotype Ia multilocus sequence type ST-7 isolate from a
      clinical case of human neonatal meningitis caused disease and death in Nile
      tilapia (Oreochromis niloticus).

PMID- 19402965
TI  - Evaluation of surveillance methods for staphylococcal toxic shock syndrome.
AB  - We compared passive surveillance and International Classification of Diseases,
      9th Revision, codes for completeness of staphylococcal toxic shock syndrome (TSS)
      surveillance in the Minneapolis-St. Paul area, Minnesota, USA. TSS-specific codes
      identified 55% of cases compared with 30% by passive surveillance and were more
      sensitive (p = 0.0005, McNemar chi2 12.25).

PMID- 19402967
TI  - Cowpox virus transmission from pet rats to humans, Germany.
AB  - We describe a cluster of cowpox virus (CPXV) infections in humans that occurred
      near Munich, Germany, around the beginning of 2009. Previously, only sporadic
      reports of CPXV infections in humans after direct contact with various animals
      had been published. This outbreak involved pet rats from the same litter.

PMID- 19402969
TI  - Babesiosis acquired through blood transfusion, California, USA.
AB  - Babesiosis was reported in a California resident who received a transfusion of
      blood products collected in the disease-endemic northeastern region of the United
      States. Babesiosis should be considered year-round in the diagnosis of febrile
      and afebrile patients with abnormal blood cell counts who have received blood
      products from disease-endemic areas.

PMID- 19402968
TI  - Cowpox virus transmission from pet rats to humans, France.
AB  - In early 2009, four human cases of cowpox virus cutaneous infection in northern
      France, resulting from direct contact with infected pet rats (Rattus norvegicus),
      were studied. Pet rats, originating from the same pet store, were shown to be
      infected by a unique virus strain. Infection was then transmitted to humans who
      purchased or had contact with pet rats.

PMID- 19402971
TI  - Probable congenital babesiosis in infant, new jersey, USA.
AB  - Only 2 neonates with transplacentally or perinatally acquired (congenital)
      babesiosis have been reported. We describe a probable third congenital case of
      babesiosis in a 26-day-old infant; transmission was determined on the basis of a
      blood smear from the infant (15% parasitemia) and serologic results from the
      infant and mother.

PMID- 19402972
TI  - Genotype distribution and sequence variation of hepatitis E virus, Hong Kong.
AB  - Most acute cases of infection with hepatitis E virus (HEV) in Hong Kong were
      autochthonous, sporadic, and occurred in older adults. All except 1 isolate
      belonged to genotype 4; most were phylogenetically related to swine isolates. The
      epidemiology is similar to that in industrialized countries, where zoonosis is
      the major source of HEV infection in humans.

PMID- 19402973
TI  - Canine leishmaniasis in southeastern Spain.
AB  - To examine prevalence changes and risk factors for canine leishmaniasis, we
      conducted a cross-sectional seroprevalence study and a survey during April-June
      2006. Seroprevalence had increased at the meso-Mediterranean bioclimatic level
      over 22 years. Risk was highest for dogs that were older, large, lived outside,
      and lived at the meso-Mediterranean level.

PMID- 19402974
TI  - Real-time surveillance for respiratory disease outbreaks, Ontario, Canada.
AB  - To validate the utility of a chief complaint-based emergency department
      surveillance system, we compared it with respiratory diagnostic data and calls to
      Telehealth Ontario about respiratory disease. This local syndromic surveillance
      system accurately monitored status of respiratory diseases in the community and
      contributed to early detection of respiratory disease outbreaks.

PMID- 19402975
TI  - Possible seasonality of Clostridium difficile in retail meat, Canada.
AB  - We previously reported Clostridium difficile in 20% of retail meat in Canada,
      which raised concerns about potential foodborne transmissibility. Here, we
      studied the genetic diversity of C. difficile in retail meats, using a broad
      Canadian sampling infrastructure and 3 culture methods. We found 6.1% prevalence
      and indications of possible seasonality (highest prevalence in winter).

PMID- 19402976
TI  - Novel respiratory virus infections in children, Brazil.
AB  - Recently discovered respiratory viruses were detected in 19 (9.2%) of 205 nasal
      swab specimens from children in Brazil with respiratory illnesses. Five each were
      positive for human metapneumovirus (HMPV) alone and human bocavirus (HBoV) alone,
      3 for human coronaviruses (HCoV-HKU1 or -NL63) alone, and 6 for more than 1
      recently discovered virus.

PMID- 19402977
TI  - Reduced fluoroquinolone susceptibility in Salmonella enterica isolates from
      travelers, Finland.
AB  - We tested the fluoroquinolone susceptibility of 499 Salmonella enterica isolates
      collected from travelers returning to Finland during 2003-2007. Among isolates
      from travelers to Thailand and Malaysia, reduced fluoroquinolone susceptibility
      decreased from 65% to 22% (p = 0.002). All isolates showing nonclassical
      quinolone resistance were from travelers to these 2 countries.

PMID- 19402978
TI  - Molecular epidemiology of feline and human Bartonella henselae isolates.
AB  - Multiple locus variable number tandem repeat analysis was performed on 178
      Bartonella henselae isolates from 9 countries; 99 profiles were distributed into
      2 groups. Human isolates/strains were placed into the second group. Genotype I
      and II isolates shared no common profile. All genotype I isolates clustered
      within group B. The evolutive implications are discussed.

PMID- 19402979
TI  - Clostridium difficile in ready-to-eat salads, Scotland.
AB  - Of 40 ready-to-eat salads, 3 (7.5%) were positive for Clostridium difficile by
      PCR. Two isolates were PCR ribotype 017 (toxin A-, B+), and 1 was PCR ribotype
      001. Isolates were susceptible to vancomycin and metronidazole but variably
      resistant to other antimicrobial drugs. Ready-to-eat salads may be potential
      sources for virulent C. difficile.

PMID- 19402980
TI  - Clostridium difficile in retail meat products, USA, 2007.
AB  - To determine the presence of Clostridium difficile, we sampled cooked and
      uncooked meat products sold in Tucson, Arizona. Forty-two percent contained
      toxigenic C. difficile strains (either ribotype 078/toxinotype V [73%] or
      027/toxinotype III [NAP1 or NAP1-related; 27%]). These findings indicate that
      food products may play a role in interspecies C. difficile transmission.

PMID- 19402981
TI  - Bovine kobuvirus in europe.

PMID- 19402982
TI  - Candidate porcine Kobuvirus, China.

PMID- 19402983
TI  - Postoperative panophthalmitis caused by Whipple disease.

PMID- 19402984
TI  - Klebsiella pneumoniae Carbapenemase, Canada.

PMID- 19402985
TI  - Cryptosporidium sp. rabbit genotype, a newly identified human pathogen.

PMID- 19402986
TI  - Acceptance of public health measures by air travelers, Switzerland.

PMID- 19402987
TI  - Near-fatal multiple organ dysfunction syndrome induced by Plasmodium malariae.

PMID- 19402988
TI  - Pulmonary involvement and leptospirosis, Greece.

PMID- 19402989
TI  - Chikungunya outbreak, Singapore, 2008.

PMID- 19402990
TI  - Vancomycin-resistant enterococci, Point Barrow, Alaska, USA.

PMID- 19402991
TI  - Use of templates to identify source of norovirus outbreak.

PMID- 19402992
TI  - Epidemiologic questions from anthrax outbreak, Hunter Valley, Australia.

PMID- 19402993
TI  - Distinct ecologically relevant strains of Anaplasma phagocytophilum.

PMID- 19402994
TI  - Ovine herpesvirus 2 infection in Foal, Brazil.

PMID- 19402996
TI  - Campylobacter jejuni in penguins, Antarctica.

PMID- 19402995
TI  - Community-acquired methicillin-resistant Staphylococcus aureus ST398 infection,
      Italy.

PMID- 19402997
TI  - Acute diarrhea in children after 2004 tsunami, Andaman Islands.

PMID- 19402998
TI  - Population-attributable risk estimates for Campylobacter infection, Australia.

PMID- 19403000
TI  - Nature isn't what it used to be.

PMID- 19403001
TI  - Respiratory function decline and DNA mutation in mitochondria, oxidative stress
      and altered gene expression during aging.
AB  - Aging is a biological process that is characterized by the gradual loss of
      physiological function and increases in the susceptibility to disease of an
      individual. During the aging process, a wide spectrum of alterations in
      mitochondria and mitochondrial DNA (mtDNA) has been observed in somatic tissues
      of humans and animals. This is associated with the decline in mitochondrial
      respiratory function; excess production of the reactive oxygen species (ROS);
      increase in the oxidative damage to mtDNA, lipids and proteins in mitochondria;
      accumulation of point mutations and large-scale deletions of mtDNA; and altered
      expression of genes involved in intermediary metabolism. It has been demonstrated
      that the ROS may cause oxidative damage and mutations of mtDNA and alterations of
      the expression of several clusters of genes in aging tissues and senescent cells.
      We found that intracellular levels of hydrogen peroxide (H2O2) and oxidative
      damage to DNA in the tissue cells and skin fibroblasts of old donors were higher
      than those of young donors. In H2O2-induced senescent skin fibroblasts, we
      observed an increase in the protein expression and activity levels of manganese
      dependent superoxide dismutase and a concurrent decrease in the activity of
      cytochrome c oxidase and the rate of oxygen consumption. Moreover, the mRNA and
      protein expression levels of pyruvate dehydrogenase (PDH) were decreased but
      those of PDH kinase and lactate dehydrogenase were increased in senescent skin
      fibroblasts. The changes in the expression of these enzymes suggest a metabolic
      shift from mitochondrial respiration to glycolysis as a major supply of ATP in
      aging human cells. On the other hand, recent studies on mitochondrial mutant
      mice, which carry a proofreading deficient subunit of DNA polymerase gamma,
      revealed that mtDNA mutations accumulated in somatic tissues in the mice that
      displayed prominent features of aging. Taken together, we suggest that the
      respiratory function decline and increase in the production of the ROS in
      mitochondria, accumulation of mtDNA mutation and oxidative damage, and altered
      expression of a few clusters of genes that culminated in the metabolic shift from
      mitochondrial respiration to glycolysis for major supply of ATP were key
      contributory factors in the aging process in the human and animals.

PMID- 19403002
TI  - Revascularization in the tendon graft following anterior cruciate ligament
      reconstruction of the knee: its mechanisms and regulation.
AB  - In anterior cruciate ligament (ACL) reconstruction, slow graft maturation may
      result in graft failure or elongation during the postoperative rehabilitation
      period. Vascular endothelial growth factor (VEGF) is a potent mediator of
      angiogenesis. The findings of recent studies suggest that VEGF application is a
      potential strategy to accelerate angiogenesis in the graft after ACL
      reconstruction. However, the biomechanical results indicate that exogenous VEGF
      application decreases the stiffness of the grafted tendon at least temporarily.
      Therefore, we should take into account this adverse effect of exogenous VEGF
      application on the mechanical characteristics of the grafted tendon.

PMID- 19403003
TI  - Postmenopausal hormone therapy and risk of breast cancer.
AB  - Risks from hormone use among postmenopausal women will be particularly important
      in the future, given the worldwide increase in the number of older women in the
      population. Recent randomized clinical trials and epidemiological studies have
      reported various opinions on the association between the risk of breast cancer
      and postmenopausal hormone therapy (HT), especially the differences between
      therapy with unopposed estrogen and combined estrogen-progestin. The currently
      available data do not provide sufficient evidence to prove a causal association
      between postmenopausal HT and breast cancer. However, a possible risk of breast
      cancer associated with long-term HT usage should not be ignored, given that the
      degree of association between breast cancer and postmenopausal HT remains
      controversial. Unanswered questions include whether HT has a positive impact on
      breast cancer, and whether different types and routes of estrogen and
      progestogens, as well as the duration and cessation of HT use have different
      impacts on this disorder. Despite this, HT is still the most effective method of
      relieving climacteric symptoms for many postmenopausal women. Since the effect of
      HT on breast cancer risk may be related to individual susceptibility, we
      recommend close follow-up through mammography and/or breast sonography and an
      even more detailed evaluation of the potential of exogenous hormones inducing
      epithelial hyperplasia in those with increased breast density or any other high
      risk factors.

PMID- 19403005
TI  - Impact of gender, viral transmission and aging in the prevalence of hepatitis B
      surface antigen.
AB  - BACKGROUND: Age, gender, and perinatal infection are associated with
      hepatocarcinogenesis. The influence of perinatal transmission in chronic
      hepatitis B virus infection between genders at different ages is not well
      documented. METHODS: A consecutive series of individuals who had general check
      ups and three groups of relatives of patients with hepatocellular carcinoma were
      analyzed. Siblings of index cases and children of female index cases represented
      groups with high perinatal transmission, while children of male index cases
      represented a low perinatal transmission group. RESULTS: A total of 45,035
      individuals who had general check-ups and 14,513 first degree relatives of
      patients with hepatocellular carcinoma were included. The families of patients
      with hepatocellular carcinoma included 4,455 siblings of index cases, 7,111
      children of male index cases, and 2,947 children of female index cases. The
      prevalence of hepatitis B surface antigen (HBsAg) was high in groups with high
      perinatal infection and in men. Gender differences in the prevalence of HBsAg
      diminished in children of female index cases and siblings of index cases, and in
      all groups after the age of 60 years. The prevalence of HBsAg declined with
      increasing age in all groups, with the highest decline in male siblings of index
      cases ( 1.37% per year) and the lowest in female children of male index cases (
      0.05% per year) in the 35-59 year-old period. Hepatitis C antibody was higher in
      women (5.7%) than in men (4.0%) in the general check-up group. CONCLUSIONS:
      Females were less susceptible to become HBsAg carriers if HBV was not transmitted
      during the perinatal period. The prevalence of HBsAg declined significantly in
      high perinatal infection groups, implying that neonatal tolerance does not
      endure.

PMID- 19403006
TI  - Reliability and validity of the 20-item taiwan version of the borderline
      personality inventory.
AB  - BACKGROUND: The Borderline Personality Inventory (BPI) is a self-reported
      questionnaire for screening patients with borderline personality disorder. This
      study aims to construct and validate a shorter version of the original 53-item
      BPI suitable for use in Taiwan. METHODS: A two-stage translation of the BPI was
      conducted and modified into colloquial language for use in Taiwan. It was tested
      against 3 groups of patients (borderline personality disorder, schizophrenia,
      neurotic disorders) and healthy subjects. After item analyses, a 20-item BPI was
      selected (BPI-T20), and its internal consistency was assessed. The validity was
      examined using relative operating characteristic (ROC) analysis. RESULTS:
      Altogether, 544 subjects successfully completed the study. The Cronbach's alpha
      coefficient was 0.92, while 3 factors were extracted from the questionnaire. The
      BPI-T20 had significant discriminatory power with satisfactory validity for
      borderline personality disorder, with an area under the ROCcurve of 0.93 at a cut
      off point of 11/12. The sensitivity and specificity were 89.8% and 82.8%
      respectively, with a misclassification rate of 14.7%. CONCLUSION: The BPI-T20
      appears to be reliable, effective and valid in screening borderline personality
      disorder. It could be applied in large-scale epidemiological community surveys.

PMID- 19403004
TI  - Molecular mechanisms of psychostimulant addiction.
AB  - Drug addiction represents a pathological form of neuroplasticity along with the
      emergence of aberrant behaviors involving a cascade of neurochemical changes
      mainly in the brain's rewarding circuitry. The aberrant behavioral phenotypes can
      be assessed by an animal model of drug-induced behavioral sensitization, which is
      characterized by an initiation stage that is formed in the ventral tegmental area
      and a behavioral expression stage determined mainly in the nucleus accumbens.
      Numerous studies during past decades demonstrate that the mesocorticolimbic
      dopamine pathway plays an essential role in the development of behavioral
      sensitization. Moreover, a series of cellular signaling pathways and gene
      expression determine the severity of addictive behaviors. In addition to the well
      characterized dopamine D1 receptor-mediated cAMP/protein kinase A up-regulation
      in the nucleus accumbens, recent reports indicate the cellular mediator dopamine-
      and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and transcription
      regulator DeltaFosB are associated with the accumbal PKA pathway to modulate the
      development of behavioral sensitization. The finding of cAMP-independent and
      dopamine D2 receptor-mediated Akt/GSK3 in activation in the nucleus accumbens of
      behaviorally sensitized animals implies that a signal cascade down-stream of both
      dopamine D1 and D2 receptors comprises the mainstay of the addiction network.
      This review outlines the cellular pathways that have been demonstrated to
      participate in psychostimulant addiction, focused particularly in the nucleus
      accumbens.

PMID- 19403007
TI  - Laser photocoagulation combined with subtenon injection of triamcinolone
      acetonide for diabetic cystoid macular edema.
AB  - BACKGROUND: To compare the effects of laser photocoagulation combined with
      subtenon injection of triamcinolone acetonide with photocoagulation alone, for
      diabetic cystoid macular edema. METHODS: This retrospective comparative study
      analyzed data for 34 eyes with cystoid macular edema treated with
      photocoagulation alone (n=17) or combined with triamcinolone (n=17). All patients
      were followed for 6 months after the procedure. Laser photocoagulation included
      focal photocoagulation focused on microaneurysms and light grid photocoagulation
      spread over the edematous retina. Subtenon injection of triamcinolone (20 mg/0.5
      cc) was performed in the superior-temporal conjunctiva. RESULTS: In the
      photocoagulation only group, the pretreatment mean visual acuity (VA) measured by
      the logarithm of the minimum angle of resolution (LogMAR) was 1.06+/-0.49. The
      number of laser spots was 34+/-10. The 6 -month post- treatment mean LogMAR was
      1.13+/-0.60. In the photocoagulation combined with triamcinolone group, the
      pretreatment mean LogMAR was 1.31+/-0.49. The number of laser spots was 42+/-14.
      The 6 -month post- treatment mean LogMAR was 1.26+/-0.49. In the photocoagulation
      only group, 7 eyes had stable vision (improved, stable or loss of <2 lines) and 8
      eyes had vision loss (loss>or=2 lines). In the photocoagulation combined with
      triamcinolone group, 15 eyes had stable vision and 2 eyes had vision loss. Fewer
      eyes had vision loss in the photocoagulation combined with triamcinolone group.
      (chi-square test, p=0.024). CONCLUSIONS: This study, with a follow-up of 6
      months, suggests that subtenon injection of triamcinolone combined with macular
      photocoagulation provides a better chance of stabilizing vision loss in patients
      with diabetic cystoid macular edema than photocoagulation alone.

PMID- 19403008
TI  - Ruling out piriformis syndrome before diagnosing lumbar radiculopathy.
AB  - BACKGROUND: Piriformis syndrome (PS), a rare cause of sciatica, is usually
      diagnosed only after excluding all other possibilities. But this principle is
      being challenged because of the number of patients with PS who have had
      ineffective lumbar decompressive surgery after positive findings on image study.
      METHODS: From 2001 to 2004, twelve patients with piriformis syndrome diagnosed by
      physical examination were retrospectively enrolled in this study. Indicators of
      piriformis syndrome include a positive Freiberg sign and local tenderness over
      the piriformis tendon. All patients received local injection of triamcinolone
      acetonide and lidocaine into the piriformis tendon. The course of diagnosis and
      treatment was reviewed retrospectively from patient records and patient
      recollections. RESULTS: Of seven (58.3%) patients who had positive findings on
      computed tomography (CT) or magnetic resonance imaging (MRI) studies of the
      lumbar spine, four had previously undergone unsuccessful lumbar surgeries but
      were responsive to local injection and three received the injection first. Two of
      those three required no lumbar discectomy thereafter. However, one patient
      subsequently underwent lumbar decompression surgery because of failed response to
      the local injection. Three patients had negative CT or MRI findings, and two
      received no CT or MRI study. According to our diagnostic flowchart for PS,
      further lumbar surgery was unnecessary for eleven of the twelve patients at
      follow-up. CONCLUSIONS: According to experience in this series, a Freiberg test
      and local injection should be performed first to rule out PS in patients with
      unilateral sciatica. If symptoms are relieved by local injection and further
      physical therapy for PS, unnecessary lumbar surgery can be avoided.

PMID- 19403009
TI  - Two-stage reimplantation of infected hip arthroplasties.
AB  - BACKGROUND: Although two-stage reimplantation for infected hip arthroplasty has a
      high success rate, the protocols of the antibiotic therapy after resection
      arthroplasty have varied in different reports. The purpose of this study was to
      evaluate the clinical outcomes of two-stage reimplantation for infected hip
      arthroplasty using our protocol of combined parenteral and oral antibiotic
      therapy and the criterion for reimplantation. METHODS: Forty-seven patients (48
      hips) with infected hip arthroplasty were treated with two-stage reimplantation
      using interim antibiotic-impregnated cement beads with an average 2.6 weeks of
      parenteral antibiotic and 6 weeks of oral antibiotic therapy. The timing for
      reimplantation was determined using the values of erythrocyte-sedimentation rate
      (ESR) and C-reactive protein (CRP) with no clinical signs of infection. The
      average follow-up period was 5.6 years. RESULTS: Forty-six (96%) hips were free
      of recurrent infection according to clinical examination and laboratory tests at
      the latest follow up. All 48 hips had negative tissue culture results obtained at
      the second-stage reimplantation except one which resulted in a recurrent
      infection. The average interim period of time from the first-stage procedure to
      reimplantation was 5.4 months (range, 2-24 months). Two hips had recurrent
      infections after reimplantation. The mean Harris hip score improved from 26
      points preoperatively to 83 points at the latest follow up. Thirty-five patients
      (74%) achieved excellent or good results. CONCLUSIONS: Two-stage reimplantation
      of an infected hip arthroplasty can achieve a high success rate using the
      protocol of aggressive surgical debridement, local antibiotic-loaded cement
      beads, combined parenteral and oral antibiotic therapy and reimplantation after
      normalization of ESR and CRP levels.

PMID- 19403010
TI  - The different clinical and liver pathological characteristics between the
      newborns and infants with choledochal cysts.
AB  - BACKGROUND: This study was undertaken to investigate the different clinical
      presentations of newborns and older infants with choledochal cysts, and their
      liver pathological changes. METHODS: The medical records of patients who were
      diagnosed with choledochal cysts younger than 1 year old at our hospital from
      March 1991 through November 2006 were reviewed. Patients were divided into two
      groups: the newborn group, who presented before 1 month old including those
      antenatally diagnosed patients; and the infant group, who presented at 1 month to
      12 months old. All of the patients' clinical data, including the operative,
      pathological reports and outcomes were studied and analyzed using the Chi-square
      and student-t tests. RESULTS: There were 35 patients included in the study.
      According to the Todani's classification, 74.2% of choledochal cysts were type I.
      Using Chi-square and student-t tests, the infant group had significantly higher
      pre-operative morbidity, abnormal levels of serum transaminase, gamma trans
      peptide (gamma-GT), and grade of liver fibrosis (>or=grade 2) (p<0.05). The post
      operative complications were not statistically significant between newborn and
      infant groups. CONCLUSION: Both groups had favorable outcomes after surgical
      intervention. We suggest that surgical.

PMID- 19403011
TI  - Sonographic findings in esophageal achalasia.
AB  - BACKGROUND: There are only three reports using conventional sonography to detect
      the gastroesophageal junction through the left lobe liver window in patients with
      achalasia, and the results were inconsistent. This study further characterizes
      the sonographic features of achalasia and compares them to characteristics of
      subjects with gastroesophageal malignancies. METHODS: Conventional sonography was
      performed in 21 patients with achalasia (mean age 49.0 years, 11 male and 10
      female, group A); 15 patients with malignancies at the gastroesophageal junction
      (n=10) and cardiac of the stomach (n=5) (mean age 55.3 years, 11 male and 4
      female, group B); and 30 subjects with functional dyspepsia (mean age: 38.3
      years, 15 male and 15 female, control group C). RESULTS: The median esophageal
      wall thicknesses were 5.1+/-2.3 mm (group A), 19.5+/-7.8 mm (group B), and 3.3+/
      1.2 mm (group C). However, there was overlap in the esophageal wall thickness in
      groups A and C. Sonographic features in group A were regular hypoechoic
      thickening of the wall at the gastroesophageal junction; in group B, we found
      irregular hypoechoic thickening of the wall. Control subjects had a regular
      hypoechoic gastroesophageal wall. Dilated lumens of the distal esophagus were
      seen in all achalasia patients. CONCLUSION: Although conventional sonography is
      not a diagnostic tool for achalasia, it provides interesting sonographic
      information. It cannot reveal each layer of the wall of the lumen as endoscopic
      ultrasound does, but it may tentatively differentiate achalasia from malignancies
      and assists clinicians when endoscopic ultrasound is not available.

PMID- 19403012
TI  - Survey of short-term patient satisfaction after surgery for obstructive sleep
      apnea.
AB  - BACKGROUND: To investigate the level of satisfaction of patients who received
      surgery for obstructive sleep apnea (OSA). METHODS: A patient satisfaction survey
      (PSS) was administered three months after surgery to 76 patients who received
      either a uvulopalatopharyngoplasty (UPPP) alone, or in combination with a
      septomeatoplasty (SMP), or a midline laser glossectomy (MLG). Patient
      satisfaction determinants were also explored. RESULTS: In general, 93.4% of
      patients rated their overall satisfaction as "excellent" or "very good". High
      satisfaction levels (excellent + very good >/= 90%) were observed in the
      dimensions of "professional skill", "personal manner", and "explanation of
      condition". By contrast, lower satisfaction levels (excellent + very good< 90 %)
      were observed for "perioperative discomfort". There were no significant
      differences among the UPPP alone, UPPP + SMP, and UPPP +MLG groups for any
      dimension of satisfaction (p> 0.05). Older patients had decreased overall levels
      of satisfaction (adjust R (2) = 0.1, p = 0.02). CONCLUSIONS: The preliminary
      results reveal a high overall level of satisfaction after surgery for OSA in this
      short-term survey. However, modest satisfaction with perioperative discomfort was
      also noted. Combined nasal or tongue base surgeries can be performed with patient
      satisfaction comparative to that of UPPP alone. Age may confound satisfaction
      levels in patients receiving OSA surgery.

PMID- 19403013
TI  - Cerebral venous thrombosis as the initial presentation of Behcet's disease.
AB  - Neurological symptoms are rare manifestations of Behcet's disease. In this paper,
      we report cerebral venous thrombosis as the initial presentation of Behcet's
      disease in a 40 yearold man. Our patient presented with a six-week history of
      headache, progressive loss of vision in the right eye and recurrent oral ulcers.
      Physical examination revealed oral ulcers and posterior synechia in the right eye
      with loss of light perception. Fundoscopic examination showed evidence of retinal
      vasculitis. Magnetic resonance imaging (MRI) and magnetic resonance venography
      (MRV) of the brain showed superior sagittal, left transverse, and left sigmoid
      sinus venous thrombosis. A diagnosis of Behcet's disease was made based on
      clinical criteria. Treatment with methylpredinsolone, cyclophosphamide, and
      azathioprine as well as anticoagulation was done with significant clinical
      improvement.

PMID- 19403014
TI  - Sternocleidomastoid muscle flap: an option to seal off the esophageal leakage
      after free jejunal flap transfer--a case report.
AB  - Necessary requirements for the successful management of an esophageal fistula are
      the following: functional closure of the defect, control of infection, shortened
      period of hospitalization, and minimal donor-site morbidity. A
      sternocleidomastoid (SCM) muscle flap meets those requirements. Furthermore, the
      SCM muscle flap is already a well established treatment for non-oncologic
      patients, although the procedure has received criticism for head and neck
      reconstruction in patients with malignant disease of the upper aerodigestive
      tract. In this report we describe the utility of a SCM muscle flap, as a buttress
      for repairing a frank clinical leak after esophageal reconstruction with a free
      jejunal flap, in a selected patient with a clinically N0 neck. No clinical
      leakage was found postoperatively. After a two-year of follow-up, the patient
      could eat solids without the need for additional nutritional supplementation. No
      tumor recurrence was noted.

PMID- 19403015
TI  - [Progress in diagnosis and treatment of liver cirrhosis].

PMID- 19403016
TI  - [The role of transjugular intrahepatic portosystemic shunt in the management of
      portal hypertension].

PMID- 19403017
TI  - [Long-term decreased portal pressure in cirrhotic patients with portal
      hypertension: reality or dream?].

PMID- 19403019
TI  - [Therapeutic and prevention strategies of gastroesophageal varices and variceal
      hemorrhage in cirrhosis].

PMID- 19403018
TI  - [Bone marrow stem cells for treatment of liver cirrhosis].

PMID- 19403020
TI  - [Portal hypertensive gastropathy].

PMID- 19403021
TI  - [Diagnosis and treatment of hepatopulmonary syndrome].

PMID- 19403022
TI  - [Ischemic hepatitis in hepatitis B related liver cirrhotic patients with upper
      gastrointestinal hemorrhage: clinical features and prognostic implications].
AB  - OBJECTIVE: To investigate the incidence, clinical features and prognostic
      implications of ischemic hepatitis in hepatitis B related liver cirrhotic
      patients with upper gastrointestinal hemorrhage. METHODS: By retrospective review
      of the medical records of all 264 inpatients with upper gastrointestinal
      hemorrhage of hepatitis B related liver cirrhosis from January 1st 2007 to
      November 30th 2008, 11 patients with ischemic hepatitis (IH) were identified. The
      clinical features and prognostic implications were compared between the IH
      patients and 30 patients without ischemic hepatitis (control group). RESULTS: The
      incidence of ischemic hepatitis was 4.17% in hepatitis B related liver cirrhotic
      patients with upper gastrointestinal hemorrhage. The patients in IH group were
      younger than those in control group, the average age was (43.1+/-5.7) in IH group
      and (52.3+/-11.1) in control group (P=0.013). The serum alanine aminotransferase
      and aspartate aminotransferase were increased more than 20-fold above the upper
      limit of normal values, and returned to normal values within 10 days. Compared to
      the control group, total bilirubin, lactate dehydrogenase, alkaline phosphates,
      gamma-glutamyltransferase, blood urea nitrogen, creatinine, and white blood cells
      were increased, while serum cholinesterase was decreased in IH group (P<0.05).
      The fatality rate of ischemic hepatitis was much higher than that of control
      group (54.5% vs 16.7%, P=0.041). The main causes of death in IH group were
      infection, hepatorenal syndrome and hepatic encephalopathy. The patients in IH
      group lost 200 to 3600 milliliter blood, and hemorrhagic shock occurred in 63.6%
      (7/11) of IH patients. Therefore the bleeding volume was not correlated with the
      occurrence rate of ischemic hepatitis. CONCLUSION: Ischemic hepatitis may occur
      secondary to upper gastrointestinal hemorrhage in hepatitis B related liver
      cirrhosis. The risk factors of ischemic hepatitis in cirrhositic patients with
      upper gastrointestinal hemorrhage are young and with hemorrhagic shock, and poor
      liver function. It is important to use antibiotics in time to improve the
      prognosis of these patients.

PMID- 19403023
TI  - [The effect of portal hypertension on prognosis in patients with decompensated
      liver cirrhosis].
AB  - OBJECTIVE: To evaluate the effect of portal hypertension on prognosis in patients
      with decompensated liver cirrhosis. METHODS: The clinical data of decompensated
      cirrhosis patients in our hospital, between 2003 and 2006, were retrospected and
      followed up. Model for end-stage liver disease (MELD) score and Child-Turcotte
      Pugh (CTP) classification was calculated using the standard formula. Kaplan-Meier
      survival analysis was used to compare the mortality in subgroups ranked by the
      syndromes. Cox proportional hazards regression was used to evaluate the effect of
      the syndromes on prognosis. RESULTS: A cohort of 322 patients was admitted in
      this study at the end of the follow-up. The mortality of variceal bleeding,
      hepatic encephalopathy, a large volume ascites, spontaneous bacterial
      peritonitis, the type I and type II hepatorenal syndrome was 45.9%, 79.4%, 66.7%,
      100%, 100% and 84.6% respectively. On the whole, the occurrence of all the
      syndromes was correlated with CTP classification and MELD score. Kaplan-Meier
      survival analysis showed that all of these syndromes, except for low to medium
      volume of ascites, significantly affected the survival rate (P<0.01). In Cox
      regression analysis, all the syndromes were the independent predictors of
      prognosis, the regression coefficient values of hepatic encephalopathy,
      spontaneous bacterial peritonitis, type I and type II hepatorenal syndrome,
      variceal bleeding and ascites were 0.973, 0.928, 0.935, 0.866, 0.464 and 0.369
      respectively. CONCLUSIONS: The portal hypertensive syndromes have significant
      effect on the prognosis of the patients with decompensated cirrhosis, hepatic
      encephalopathy is the worst one.

PMID- 19403024
TI  - [S gene mutations in HBsAg/HBsAb double positive chronic hepatitis B patients].
AB  - OBJECTIVES: To investigate S gene mutations in HBsAg/HBsAb double positive
      chronic hepatitis B patients. METHODS: HBV S gene from 8 patients (Group A) with
      HBsAg (+)/HBsAb (+) and 9 patients (Group B) with HBsAg (+)/HBsAb (-)was
      amplified by polymerase chain reaction (PCR) and sequencing. Both the
      distribution of genotype and serotype and the rate of MHR region were compared by
      Fisher's exact test. The mutation rate of both the DNA level and amino acid level
      was compared by t test. RESULTS: No significant difference in distribution of
      genotypes was found between the two groups (P=0.153). In group A, 2 were genotype
      B, 6 were genotype C; In group B, 6 were genotype B, 3 were genotype C. No
      significant difference in distribution of serotypes was found between the two
      groups, either (P=0.218). In group A, 2 were adw, 5 were adr, 1 was ayr; In group
      B, 6 were adw, 3 were adr. The mutation rate of Pre-S1 region at both the DNA
      level (2.29% vs 1.80%, t=2.66, P more than 0.05) and the amino acid level (2.66%
      vs 1.59%, t=1.39, P>0.05) was not significantly different between these two
      groups; the mutation rate of Pre-S2 region in group A patients was significantly
      higher than that in group B at the DNA level (1.74% vs 0.91%, t=4.68, P<0.01),
      but not higher at the amino acid level (3.18% vs 2.05%, t=1.85, P>0.05), the
      mutation rate of S region in group A patients was significantly higher than that
      in group B at both the DNA level (2.13% vs 0.81%, t=6.00, P<0.01) and the amino
      acid level (4.37% vs 1.52%, t=5.32, P<0.01). Amino acid substitutions were found
      both within and beyond the MHR region. The rate of "a" determinant mutations in
      these two groups was also found to be significantly different (P<0.05).
      CONCLUSION: Higher HBV S gene mutation rate exists in HBsAg/HBsAb double positive
      patients than that in HBsAg (+)/HBsAb (-) patients.

PMID- 19403025
TI  - [Analysis of spontaneous decline of HBV DNA in chronic hepatitis B patients in 12
      weeks].
AB  - OBJECTIVE: To analyze the spontaneous decline of HBV DNA in chronic hepatitis B
      patients in 12 weeks. METHODS: Chronic hepatitis B patients not receiving
      antiviral treatment from 2003 to 2005 were divided into two groups according to
      the baseline value of ALT and TBil. Spontaneous decline of HBV DNA were
      retrospected, and the influence of the baseline value of ALT and TBil on
      spontaneous decline of HBV DNA was analyzed. RESULTS: Total of 213 chronic
      hepatitis B patients (male 174, female 39, aged from 18 to 65) were recruited in
      this study, including 124 mild and moderate type of hepatitis B, 89 severe type
      of hepatitis B, and 19 patients (8.92%) were lost at the end of the 12th week.
      The mean baseline value of HBV DNA of all the patients was (6.66+/-1.03) log10
      copies/ml, at 12 week the mean value of HBV DNA of all the patients was (5.98+/
      1.53) log10 copies/ml (compared to baseline P<0.01), the decline value of HBV DNA
      was (0.68+/-1.46) log10 copies/ml. The mean baseline value of HBV DNA of patients
      with the severe type of hepatitis B was lower than that with the mild or moderate
      type of hepatitis B patients [(6.45+/-0.99) log10 copies/ml and (6.81+/-1.04)
      log10 copies/ml respectively] (P<0.05). However, there was no significant
      difference in the mean and the declined value of HBV DNA between these two groups
      at the 12th week (P<0.05). At the 12th week, the baseline values of ALT and TBil
      were higher in patients with HBV DNA<or=3 log10 copies/ml than those in patients
      with HBV DNA>3 log10 copies/ml (P>0.05); And there were no significant difference
      in the baseline values of ALT and TBil between patients with the declined value
      of HBV DNA>or=2 log10 copies/ml and patients with declined value of HBV DNA less
      than 2 log10 copies/ml. At the 12th week, the mean and the declined value of HBV
      DNA were similar between the patients with ALT<or=5xULN and the patients with
      ALT>5xULN at baseline. The mean baseline value of HBV DNA of patients in the
      group of patients whose baseline value of ALT<or=5xULN while TBil<or=5xULN was
      higher than that in the group of patients whose baseline value of ALT>5xULN while
      TBil>5xULN, ALT<or=5xULN while TBil>5xULN, ALT>5xULN while TBil<or=5xULN (P<0.05
      respectively), there were no significant difference in the rate of the HBV
      DNA<or=3 log10 copies/ml and the rate of the declining value of HBV DNA<or=2
      log10 copies/ml between the groups at 12 week (P>0.05 respectively). CONCLUSIONS:
      There is spontaneous decline of HBV DNA in patients with chronic hepatitis B in
      12 weeks, but the level of liver injury is not correlated with the level of
      spontaneous decline of HBV DNA in chronic hepatitis B patients in 12 weeks.

PMID- 19403026
TI  - [The immunization effects of HBV core antigen and surface antigen fusion protein
      in mice].
AB  - OBJECTIVE: To evaluate the immunization effects of HBV core antigen and surface
      antigen fusion protein. METHODS: The DNA fragments encoding HBsAg 100-162 aa;
      HBcAg 1-78 aa and HBcAg 83-144 aa were PCR-amplified, and then cloned into pcDNA3
      plasmid. The chimeric gene was subcloned into the prokaryotic vector, pRSET-B.
      The E.coli expressed recombinant protein purified. BALB/c mice were immunized
      with recombinant protein or eukaryotic expression plasmid, humoral response and
      cellular response were examined. RESULTS: The plasmid containing the chimeric
      gene of HBsAg and HBcAg induced effective anti-HBs antibody response and strong
      HBcAg specific lymphocyte proliferative response, but could not induce anti-HBc
      antibody response. Fusion protein induced strong anti-HBs and anti-HBc antibody
      response, and it also caused significant HBcAg specific lymphocyte proliferation.
      Compared to the recombinant fusion protein, the plasmid containing the chimeric
      gene of HBsAg and HBcAg can induce more effective cellular response but weaker
      humoral response. CONCLUSION: Compared to the recombinant fusion protein, the
      plasmid containing the chimeric gene of HBsAg and HBcAg is a more effective
      vaccine.

PMID- 19403027
TI  - [Two-dimensional electrophoresis analysis of hydrophobic membrane proteome in
      mouse hepatocarcinoma cell H22].
AB  - OBJECTIVE: To compare the membrane protein profile of mouse hepatocarcinoma cell
      H22 with that of normal liver cell. METHODS: The membrane proteins in mouse
      hepatocarcinoma cell H22 and normal liver cell were extracted and their
      concentrations were determined by Bradford method. The proteins were separated by
      two-dimensional electrophoresis, and then stained with silver. The 2-DE maps were
      scanned and analyzed by Image Master 2D Platinum software. The differential
      expression protein spots were cut out from the gels, and the peptide
      fingerprinting was determined by MALDI-TOF-MS (Matrix-Assisted Laser Desorption/
      Ionization Time of Flight Mass Spectrometry), followed by matching to Swiss-Prot
      protein database by Aldente software with experimental pI and MW data. RESULTS:
      Compared to normal liver cells, 8 membrane proteins, including sulfatase
      modifying factor 2, protein kinase C and casein kinase II substrate protein 3,
      sorting and assembly machinery component 50 homolog, macrophage scavenger
      receptor types I/II, uncharacterized protein C9 or f135 homolog, tight junction
      protein ZO-2, 3-hydroxy-3- methylglutaryl-coenzyme A reductase, and vacuolar
      protein sorting-associated protein 52 homolog were upregulated in H22 cells.
      CONCLUSION: The membrane proteins involved in cell metabolism, proliferation,
      signal transduction, and skeleton, which are highly expressed in mouse
      hepatocarcinoma H22 cells, are probably related to the proliferation, invasion
      and migration of this tumor cell line.

PMID- 19403028
TI  - [Role of focal adhesion kinase in the hypoxia-induced invasion of SMMC-7721
      cells].
AB  - OBJECTIVE: To study focal adhesion kinase (FAK) expression in hypoxia-stressed
      SMMC-7721 cells and the role of FAK expression in the hypoxia-induced invasion of
      SMMC-7721 cells. METHODS: SMMC-7721 cells were cultured in 21% O2 or 1% O2. FAK
      expression was determined by Western blot. The siRNA expression vector pshRNA-FAK
      targeting to FAK and the control vector pGensil-2 were transfected into SMMC-7721
      cells. The hypoxia-induced migration and invasion ability of SMMC-7721 cells
      transfected with pshRNA-FAK were analyzed. In normoxia, invasion of SMMC-7721
      cells transfected with pcDNA3-FAK was analyzed. RESULTS: The expression of FAK
      was increased significantly in SMMC-7721 cells 24 h after hypoxia stress
      (P<0.01). The level of FAK protein was decreased by 74.6%+/-5.1% after the pshRNA
      FAK transfection in normoxia and hypoxia. The migration and invasion of SMMC-7721
      cells was increased in 1% O2 (P<0.01). However, the migration and invasion of
      SMMC-7721 cells transfected with pshRNA-FAK was decreased in 1% O2 (P<0.05).
      Overexpression of FAK significantly stimulated the invasion of SMMC-7721 cells.
      CONCLUSION: Up-regulation of FAK may play an important role in the invasion of
      SMMC-7721 cells induced by hypoxia.

PMID- 19403029
TI  - [Correlaion between serum Golph2 protein and hepatocellular carcinoma].
AB  - OBJECTIVE: To study the correlation between hepatocellular carcinoma (HCC) and
      serum Golph2 protein. METHODS: Golph2 gene was cloned by RT-PCR using RNA from
      WBF44 cell line as template, the point mutations of the cloned sequence were
      corrected by PCR, then the gene (1206 bp) was cloned into pET-21 plasmid, and the
      resulted plasmid was transformed into E.coli DH5a. The expression of 6xHis and
      Golph2 fusion protein was induced by isopropylthio-beta-D-galactoside (IPTG). The
      expression of fusion protein was detected by SDS-PAGE and Western blot, and was
      purified by Ni NTA chelating agarose. The rabbit antibody against Golph2 protein
      was obtained by immunizing 2 rabbits with the purified Golph2 protein. The
      specificity and titer of the antibody was determined by Western-blot and ELISA
      respectively. Sandwich ELISA was used to detect the level of serum Golph2
      protein. RESULTS: There were two replacement mutation and 1 deletion mutation in
      the cloned sequence contrasted to NM177937 in Genbank, including 644(T-->C, L-
      >P) , 970 (G-->A, V-->I) and 802 G deletion. The sequence was completely reversed
      by PCR. The sequence of Golph2 gene cloned into expression vector was confirmed
      by DNA sequencing. SDS-PAGE and Western blot analysis showed that Golph2 protein
      was expressed in E.coli DH5a. The antiserum could bind to the 52 kD recombinant
      protein and serum 73 kD protein specifically. The mean A450 value of ELISA for
      serum Golph2 protein were significantly higher in HCC and other liver diseases
      than that in control groups. The sensitivity and specificity for HCC were 44.5%
      and 82.0%, respectively, at the cut off value is more than or equal to 0.40.
      CONCLUSION: The polyclonal antibody against Golph2 protein is specific. The level
      of serum Golph2 is significantly higher in patients with HCC and other liver
      diseases than that in healthy controls.

PMID- 19403030
TI  - [The effect of hepatitis B virus X protein on the c-met promoter activity in
      HepG2 cells].
AB  - OBJECTIVE: To confirm the effect of hepatitis B virus X (HBx) protein on the c
      met promoter activity in HepG2 cells. METHOD: The expression of c-met protein was
      detected by western blot in HBx-transfected HepG2 cells, the human c-met promote
      activity was checked by luciferase assay using five different constructs with
      deletion or point mutation. RESULTS: HBx protein stimulated the expression of the
      c-met in HepG2 cells. The enhanced expression of c-met in HBx-transfected cells
      was mediated by the activation of AP-2 and SP-1 transcriptional activity at the c
      met promoter region (-183bp--100bp), HBx increased the invasiveness of HepG2
      cells as determined by Matrigel invasion assay. CONCLUSION: These results
      suggests that HBx induces the expression of c-met through the activation of AP-2
      and SP-1 activity at the promoter region; in addition, our data indicate that HBx
      stimulates the invasive potential of HepG2 cells.

PMID- 19403031
TI  - [Induction of SMYD3 by hepatitis B virus X gene in HepG2 cells].
AB  - OBJECTIVE: To explore the role SMYD3 and histone methylation in the
      carcinogenesis of HBV-related hepatocellular carcinoma (HCC). METHODS: HBx
      expressing plasmid was transfected into HepG2 cell, the localization of HBx and
      SMYD3 was detected by immunofluorescence, SMYD3 mRNA and protein were checked by
      real-time reverse transcription polymerase chain reaction and western blot, cell
      proliferation and apoptosis were detected by flow cytometry. RESULTS: After HBx
      transfection, HBx and SMYD3 protein were mainly localized in nucleus. HBx protein
      enhanced SMYD3 mRNA and SMYD3 expressions in HepG2. After HBx transfection,
      apoptosis of HepG2 was decreased, and cell proliferation was increased.
      CONCLUSIONS: HBx may induce the expression of histone methyltransferase SMYD3,
      which in turn stimulates cell proliferation and blocks apoptosis.

PMID- 19403032
TI  - [Effect of tea polyphenols on expression of nuclear factor kappa B].
AB  - OBJECTIVE: To investigate the effect of tea polyphenols (TP) on expression of
      nuclear factor kappa B (NF-kB) in rats with alcoholic liver diseases and in cells
      treated with alcohol. METHODS: 22 female Wistar rats were randomly divided into
      three groups: a control group, an alcohol model group and a TP plus alcohol
      group. All treatments were injected into stomach through intragastric tube. L02
      cells were divided into five groups: a control group, an alcohol treated group, a
      prevention group (cells were treated with TP for 3 days, and then treated with
      alcohol), an intervention group (cells treated with TP and alcohol), and a
      therapeutic group (cells were treated with alcohol for 3 days, and then treated
      with TP). Histopathology was observed under light microscope (LM); serum MDA, ROS
      in cells were quantified by optical density measurement; the expression of NF-kB
      and IkB was determined by RT-PCR; and the activity of NF-kB was checked with
      Electrophoretic Mobility Shift Assay (EMSA). RESULTS: LM indicated hepatocytes
      were injured obviously in the model group. Serum MDA and cells ROS in TP treated
      groups were significantly lower than the alcohol treated group. The level of NF
      kB mRNA expression in TP treated groups(rats: 0.58+/-0.16, cells: 0.60+/-0.03,
      0.59+/-0.01, 0.59+/-0.01) were significantly lower than the alcohol treated group
      (rats: 1.15+/-0.03, cells: 0.76+/-0.03) (P<0.01), the level of IkB mRNA
      expression in the prevention group, intervention group, and therapeutic group
      (0.51+/-0.01, 0.50+/-0.01, 0.50+/-0.12) were significantly higher than the
      alcohol treated group (0.61+/-0.03) (P<0.05), the difference among the three
      groups was not significant (P>0.05). The activity of NF-kB in TP treated rats(DNA
      stain: 669.85+/-41.34, Protein stain: 675.35+/-18.27) was significantly lower
      than the alcohol treated rats(DNA stain: 1410.78+/-22.19, Protein stain:1426.08+/
      33.15) (P<0.01); NF-kB activity in cells of the prevention, intervention,
      therapeutic groups (DNA stain: 713.07+/-11.91, 710.79+/-14.99, 693.45+/-71.69;
      Protein stain: 758.88+/-34.65, 753.07+/-76.78, 725.77+/-36.09) was significantly
      lower than the alcohol treated cells (DNA stain: 849.94+/-12.45, Protein stain:
      925.96+/-5.78) (P<0.01), the difference among the three TP treated groups was not
      significant (P>0.01). CONCLUSION: TP can alleviate and prevent alcohol-induced
      liver injury via inhibiting NF-kB activation.

PMID- 19403033
TI  - [Study on the relation between hemodynamics of portal system and cirrhosis portal
      hypertension].

PMID- 19403034
TI  - [Effect of YC-1 on HIF-1 alpha and VEGF expression in human hepatocarcinoma cell
      lines].

PMID- 19403035
TI  - [Establishment of human hepatocellular carcinoma cell line expressing HBx shRNA].

PMID- 19403037
TI  - [A case report of severe hepatitis patient complicated with hemo-disseminated
      lung aspergillosis].

PMID- 19403036
TI  - [The effect of thalidomine-induced NF-kappa B activation on malignant
      transformation of hepatocytes].

PMID- 19403038
TI  - [13C breath tests: a useful tool to quantify hepatic reserve function].

PMID- 19403039
TI  - UAP56- a key player with surprisingly diverse roles in pre-mRNA splicing and
      nuclear export.
AB  - Transcripts contain introns that are usually removed from premessenger RNA (MRNA)
      in the process of pre-mRNA splicing. After splicing, the mature RNA is exported
      from the nucleus to the cytoplasm. The splicing and export processes are coupled.
      UAP56 protein, which is ubiquitously present in organisms from yeasts to humans,
      is a DExD/H-box family RNA helicase that is an essential splicing factor with
      various functions in the prespliceosome assembly and mature spliceosome assembly.
      Collective evidence indicates that UAP56 has an essential role in mRNA nuclear
      export. This mini-review summarizes recent evidence for the role of UAP56 in pre
      mRNA splicing and nuclear export.

PMID- 19403040
TI  - Involvement of lymphoid inducer cells in the development of secondary and
      tertiary lymphoid structure.
AB  - During development lymphoid tissue inducer (LTi) cells are the first
      hematopoietic cells to enter the secondary lymphoid anlagen and induce lymphoid
      tissue neogenesis. LTi cells induce lymphoid tissue neogensis by expressing a
      wide range of proteins that are associated with lymphoid organogenesis. Among
      these proteins, membrane-bound lymphotoxin (LT) alpha1beta2 has been identified
      as a critical component to this process. LTalpha1beta2 interacts with the LTbeta
      receptor on stromal cells and this interaction induces up-regulation of adhesion
      molecules and production of chemokines that are necessary for the attraction,
      retention and organization of other cell types. Constitutive expression of
      LTalpha1beta2 in adult LTi cells can result in the formation of a lymphoid-like
      structure called tertiary lymphoid tissue. In this review, we summarize the
      function of fetal and adult LTi cells and their involvement in secondary and
      tertiary lymphoid tissue development in murine models.

PMID- 19403041
TI  - The ginsenoside-Rb2 lowers cholesterol and triacylglycerol levels in 3T3-L1
      adipocytes cultured under high cholesterol or fatty acids conditions.
AB  - The effects of the ginsenoside Rb2 (Rb2) on lipid metabolism were characterized
      in 3T3-L1 adipocytes to evaluate their utility for treating obesity. While the
      amounts of total cholesterol and triacylglycerol (TAG) were markedly increased in
      the adipocytes treated with high amounts of cholesterol and fetal bovine serum
      (FBS), the test groups treated with Rb2 showed levels that were close to normal.
      The effect of Rb2 on these cells was comparable to that of lovastatin. Rb2
      enhanced the expression of the sterol regulated element binding protein (SREBP)
      mRNA whereas treatment with cholesterol and FBS led to a reduction in the
      abundance of this transcript. The activity of fatty acid synthetase (FAS) was
      lower in the cholesterol group compared to the Rb2 treatment group suggesting
      that the observed decrease in cholesterol levels and activated SREBP was mediated
      by Rb2. Treatment with Rb2 also resulted in a decrease in TAG levels in
      adipocytes cultured under high fatty acid conditions. This effect was mediated by
      stimulating the expression of SREBP and Leptin mRNA, suggesting that Rb2 might be
      a valuable component capable of lowering the levels of lipids.

PMID- 19403042
TI  - Association of polymorphisms in thromboxane A2 receptor and thromboxane A
      synthase 1 with cerebral infarction in a Korean population.
AB  - Thromboxane A2 (TBXA2) is a potent vasoconstrictor in cerebral circulation and is
      a known contributor to the pathogenesis of cerebral infarction. Thromboxane A2
      synthase 1 (TBXAS1) and thromboxane A2 receptors (TBXA2R) are key components in
      TBXA2 function. We examined whether genetic variants in TBXA2R and TBXAS1 are
      risk factors for cerebral infarction by genotyping 453 Korean patients with
      noncardiogenic cerebral infarction and 260 controls. A few, specific
      polymorphisms in the TBXA2R (-3372G>C, +4710T>C and 4839T>C) and TBXAS1
      (+16184G>T, +141931A>T and +177729G>A) genes were chosen and investigated.
      Logistic regression showed the frequencies of TBXAS1+16184G>T and TBXAS1- ht3
      were significantly more frequent in cerebral infarction (P=0.002, OR=2.75 and
      P=0.01, OR=1.57, respectively), specifically in small-artery occlusion (SAO) type
      of cerebral infarction (P=0.0003 and 0.005, respectively). These results suggest
      specific TBXAS1 gene polymorphisms may be a useful marker for development of
      cerebral infarction, especially SAO type in Korean population.

PMID- 19403043
TI  - Molecular cloning, tissue distribution and quantitative analysis of two
      proopiomelanocortin mRNAs in Japanese flounder (Paralichthys olivaceus).
AB  - Proopiomelanocortin (POMC) plays an essential role in the stress response of the
      hypothalamic-pituitary-adrenal axis, and is the precursor of biologically active
      peptides such as adrenocorticotropin (ACTH), alpha-melanocyte-stimulating hormone
      (alpha-MSH), beta-melanocyte-stimulation hormone (beta-MSH) and beta-endorphin.
      We have synthesized two different forms of POMC cDNA clones, POMC-I and POMC-II,
      from a pituitary cDNA library for Paralichthys olivaceus, or Japanese flounder.
      jfPOMC-I cDNA consists of 954bp and encodes a polypeptide of 216 amino acid
      residues, whereas jfPOMC-II consists of 971bp which encode a polypeptide of 194
      amino acid residues. The high levels of jfPOMC-I and -II mRNAs detected in the
      pituitary tissue and moderate levels detected in the brain tissue plus our
      quantitative RT-PCR analysis, which showed there to be no significant difference
      between the levels of jfPOMC-I and -II mRNAs, indicate that there may be no
      functional separation between these two mRNAs in the flounder.

PMID- 19403044
TI  - Fc fusion to glucagon-like peptide-1 inhibits degradation by human DPP-IV,
      increasing its half-life in serum and inducing a potent activity for human GLP-1
      receptor activation.
AB  - The short in vivo half-life of GLP-1 prevents it from being used clinically. This
      short half-life occurs because GLP-1 is rapidly degraded by dipeptidyl peptidases
      such as DPP-IV. To overcome this obstacle, a GLP-1/Fc was constructed and
      evaluated to determine if it was degraded by DPP-IV and in serum. When the
      degradation of GLP-1/Fc by human DPP-IV and rabbit serum was compared with that
      of GLP-1 it was found to be reduced by approximately 5- and 4-fold, respectively.
      Furthermore, GLP-1/Fc showed a potent activity for human GLP-1 receptor
      activation (EC50 approximately 6 nM). Taken together, these results indicate that
      GLP-1/Fc may have an extended half-life in vivo that occurs as a result of
      inhibition of degradation by human DPP-IV. Due to the extended half life, GLP
      1/Fc may be useful for clinical treatments.

PMID- 19403045
TI  - Induction of cancer cell-specific death via MMP2 promoterdependent Bax
      expression.
AB  - Controlled gene expression in specific cells is a valuable tool for gene therapy.
      We attempted to determine whether the lentivirus-mediated Tet-On inducible system
      could be applied to cancer gene therapy. In order to select the genes that induce
      cancer cell death, we compared the ability of the known pro-apoptotreic genes,
      Bax and tBid, and a cell cycle inhibitor, p21cip1/waf1, and determined that Bax
      was the most effective. For the cancer cell-specific expression of rtTA2(S)-M2,
      we tested the matrix metalloproteinase-2 (MMP-2) promoter and determined that it
      is highly expressed in cancer cell lines, including SNU475 cells. The co
      transduction of two lentiviruses that contain sequences for TRE-Bax and rtTA2(S)
      M2, the expression of which is controlled by the MMP-2 promoter, resulted in the
      specific cell death of SNU475, whereas other cells with low MMP-2 expression did
      not evidence significant cell death. Our data indicate that the lentivirus
      mediated Tet-On system using the cancer-specific promoter is applicable for
      cancer gene therapy.

PMID- 19403046
TI  - pH-dependent surface-enhanced resonance Raman scattering of yeast iso-1
      cytochrome c adsorbed on silver nanoparticle surfaces under denaturing conditions
      at pH<3.
AB  - We measured the pH-induced spectral changes of yeast iso-1-cytochrome c on silver
      nanoparticle surfaces using surface-enhanced resonance Raman scattering (SERRS)
      at 457.9 nm. At a pH of 3, the Met80 ligand in yeast iso-1-cytochrome c is
      assumed to dissociate, leading to a marked conformational change as evidenced by
      the vibrational spectral shifts. The Soret band at 410 nm in the UV-Vis spectrum
      shifted to 396 nm at pH 3, indicating a transition from a low spin state to a
      high spin state from a weak interaction with a water molecule. Thus, SERRS
      spectroscopy can measure the pH-induced denaturalization of cyt c adsorbed on
      metal nanoparticle surfaces at a lower concentration with a better sensitivity
      than ordinary resonance Raman spectroscopy.

PMID- 19403047
TI  - Potential role of the histone chaperone, CAF-1, in transcription.
AB  - The eukaryotic genome forms a chromatin structure that contains repeating
      nucleosome structures. Nucleosome packaging is regulated by chromatin remodeling
      factors such as histone chaperones. The Saccharomyces cerevisiae H3/H4 histone
      chaperones, CAF-1 and Asf1, regulate DNA replication and chromatin assembly. CAF
      1 function is largely restricted to non-transcriptional processes in
      heterochromatin, whereas Asf1 regulates transcription together with another H3/H4
      chaperone, HIR. This study examined the role of the yeast H3/H4 histone
      chaperones, Asf1, HIR, and CAF-1 in chromatin dynamics during transcription.
      Unexpectedly, CAF-1 was recruited to the actively transcribed region in a similar
      way to HIR and Asf1. In addition, the three histone chaperones genetically
      interacted with Set2-dependent H3 K36 methylation. Similar to histone chaperones,
      Set2 was required for tolerance to excess histone H3 but not to excess H2A,
      suggesting that CAF-1, Asf1, HIR, and Set2 function in a related pathway and
      target chromatin during transcription.

PMID- 19403048
TI  - SAFB1, an RBMX-binding protein, is a newly identified regulator of hepatic SREBP
      1c gene.
AB  - Sterol regulatory element-binding protein (SREBP)-1c plays a crucial role in the
      regulation of lipogenic enzymes in the liver. We previously reported that an X
      chromosome-linked RNA binding motif (RBMX) regulates the promoter activity of
      Srebp-1c. However, still unknown was how it regulates the gene expression. To
      elucidate this mechanism, we screened the cDNA library from mouse liver by yeast
      two-hybrid assay using RBMX as bait and identified scaffold attachment factor B1
      (SAFB1). Immunoprecipitation assay demonstrated binding of SAFB1 to RBMX.
      Chromatin immunoprecipitation assay showed binding of both SAFB1 and RBMX to the
      upstream region of Srebp-1c gene. RNA interference of Safb1 reduced the basal and
      RBMX-induced Srebp-1c promoter activities, resulting in reduced Srebp-1c gene
      expression. The effect of SAFB1 overexpression on Srebp-1c promoter was found
      only in the presence of RBMX. These results indicate a major role for SAFB1 in
      the activation of Srebp-1c through its interaction with RBMX.

PMID- 19403049
TI  - The XX Ottorino Rossi award.

PMID- 19403050
TI  - Genes and the dynamics of pain control.
AB  - There are well-documented sex differences in the prevalence of various painful
      disorders. To comprehend the mechanisms underlying these differences requires an
      understanding of the molecular organisation and systems biology that are
      responsible for the pain experience. The pain system evolved to secure the
      survival of the animal under a variety of environmental constraints and needed to
      be flexible enough to compete against other behavioural needs and homeostatic
      demands. From the periphery to the cortex, mechanisms exist to facilitate or
      inhibit nociceptive signalling and it is this inherent plasticity that is thought
      to be perturbed in chronic pain states. There is limited evidence to suggest that
      polymorphisms or mutations in certain genes and gender can influence the pain
      experience but it seems likely that epigenetics and the influence of past
      experience are responsible for a substantial part of the variation between sexes
      and between individuals.

PMID- 19403051
TI  - Sexual differentiation of the human brain in relation to gender identity and
      sexual orientation.
AB  - During the intrauterine period the fetal brain develops in the male direction
      through a direct action of testosterone on the developing nerve cells, or in the
      female direction through the absence of this hormone surge. In this way, our
      gender identity (the conviction of belonging to the male or female gender) and
      sexual orientation are programmed into our brain structures when we are still in
      the womb. However, since sexual differentiation of the genitals takes place in
      the first two months of pregnancy and sexual differentiation of the brain starts
      in the second half of pregnancy, these two processes can be influenced
      independently, which may result in transsexuality. This also means that in the
      event of ambiguous sex at birth, the degree of masculinization of the genitals
      may not reflect the degree of masculinization of the brain. There is no proof
      that social environment after birth has an effect on gender identity or sexual
      orientation.

PMID- 19403052
TI  - Gender, migraine and affective disorders in the course of the life cycle.
AB  - The relationships existing between migraine and affective disorders are still far
      from clear. Despite the evidence of a high prevalence, in association, of both
      conditions, many questions remain unanswered. To what extent is the coexistence
      of migraine and affective disorders, in particular depression, genetically
      determined? How important a role is played by pregnancy? What interactions occur
      between genetic and epigenetic factors? The authors analyse all these open
      questions and review the state of the art on this intriguing topic.

PMID- 19403053
TI  - Anti-osteoporotic treatments in neurological diseases.
AB  - The constant ageing of the population has resulted in an increase in chronic
      conditions such as osteoporosis and neurodegenerative diseases as well as in
      patient comorbidity. Prolonged immobility, the use of osteopoenia-inducing drugs
      and an increased risk of falls in patients with neurological diseases have led to
      an increase in the incidence of fragility fractures, especially of the femur, in
      these patients. The consequences of these events are often dramatic, being
      associated with increased mortality, disability and worsening of cognitive and
      relational functions. Potent drugs are currently available that can reduce
      fracture risk by up to 50% with long-term safety and tolerability.
      Bisphosphonates are the agents most extensively used to prevent fragility
      fractures. Risedronate has been demonstrated to reduce fracture risk, also in
      patients with neurological conditions. Considering that osteoporosis requires
      chronic treatment, patient compliance is extremely important to obtain treatment
      efficacy.

PMID- 19403054
TI  - Gender and stroke: acute phase treatment and prevention.
AB  - Stroke is the third most common cause of death in women and a major cause of
      disability. Many aspects of stroke are similar in men and women, including
      clinical presentation, main risk factors, and distribution of the main subtypes.
      There are, however, some gender differences and specificities in stroke including
      some aspects related to treatment. Women are less likely to receive thrombolysis
      than men; however, in treated cases, the efficacy of intravenous thrombolysis is
      higher in women than in men. Hormone replacement therapy has been suggested as a
      possible strategy to reduce the occurrence of stroke in postmenopausal women but
      several clinical trials failed to show any benefit in stroke and cardiovascular
      disease prevention. Also in stroke prevention with antiplatelets there emerge
      some important gender differences: in primary prevention of stroke, aspirin was
      effective in women but not in men while in secondary prevention no gender
      differences were found with any of the available antiplatelet agents.

PMID- 19403055
TI  - Electrical stimulation in headache treatment. For separate headache(s) or for
      headache generally?
AB  - Two cases of unilateral, severe headache were treated with epidural/epicranial
      electrical stimulation, with an immediate and most favorable response. One
      patient suffered from cervicogenic headache (CEH), while the headache in the
      other one showed some similarity to Hemicrania continua (HC): unilaterality and
      some localized, ipsilateral autonomic phenomena. But, there were also sufficient
      features to alienate this picture decisively from HC: poor response to
      indomethacin and, frequently, excruciatingly severe pain. In the CEH patient, the
      electrode was anchored at the posterior, bony end of the foramen magnum. In case
      2, it was placed above and anterior to the symptomatic side ear, i.e. at the
      point of maximal pain. The headache in the latter patient may be termed: "non
      indomethacinresponsive chronic hemicrania", which may not be a rare headache. In
      both patients, the spectacular improvement has continued for the whole post
      operative period, i.e. for around five years and 11 months, respectively.

PMID- 19403056
TI  - Chronic obstructive pulmonary disease: evidence for an autoimmune component.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible
      limitation on pulmonary airflow associated with chronic inflammation and mucous
      hypersecretion (chronic bronchitis) and/or the pathological destruction of
      alveolar airspaces leading to emphysema. COPD, predominantly as a result of
      tobacco smoke exposure, represents the fourth leading cause of mortality
      worldwide and its prevalence is increasing. Despite this, much of the basic
      mechanisms which contribute to disease progression remain to be elucidated and
      current therapeutic approaches are, for the most part, based upon alleviating
      patient symptoms (bronchodilators) as opposed to treating the underlying
      pathological mechanisms triggered in response to cigarette smoke exposure. The
      classic disease paradigm suggests that an imbalance of pulmonary matrix proteases
      versus anti-proteases underlies the tissue destruction and inflammation
      associated with COPD. However, there is a growing appreciation of the complex and
      multifaceted nature of the pathological mechanisms associated with disease
      progression. Recently, there has been mounting evidence indicating that COPD
      patients exhibit many of the characteristics of a classical autoimmune response.
      We will discuss current evidence in support of this paradigm and outline how
      future therapeutic approaches may be tailored to address this.

PMID- 19403057
TI  - Dendritic cells transduced with SOCS1 gene exhibit regulatory DC properties and
      prolong allograft survival.
AB  - SOCS1 is a key regulator of cytokine signaling and is important for maintaining
      balance in the immune system. It is thought to participate in negative feedback
      loops in cytokine signaling and may be an important signal for the regulation of
      dendritic cell (DC) maturation. However, it remains unclear whether DCs
      transduced with SOCS1 exhibit characteristics of regulatory DCs and induce
      allogeneic T-cell hyporesponsiveness. In this study, we constructed adenoviral
      vector coding SOCS1 (Ad-SOCS1) that can efficiently increase SOCS1 gene
      expression in bone marrow-derived dendritic cells. DCs transduced with Ad-SOCS1
      (DC-SOCS1) expressed low levels of costimulatory and MHC molecules, were
      resistant to maturation and activation stimulation, induced allogeneic T-cell
      hyporesponsiveness, and promoted the generation of regulatory-like T cells in
      vitro. DC-SOCS1 pretreatment significantly prolonged the survival of allografts
      and led to a substantial increase in the generation of regulatory T cells. Our
      data suggest that SOCS1 inhibits DC maturation and induces regulatory DC
      generation, therefore possessing therapeutic potential to prevent rejection in
      organ transplantation.

PMID- 19403058
TI  - Computational prediction and identification of Epstein-Barr virus latent membrane
      protein 2A antigen-specific CD8+ T-cell epitopes.
AB  - Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC) is a high
      incidence tumor in Southeast Asia. Among EBV encoded proteins, latent membrane
      protein 2A (LMP2A) is an important antigen for T cell therapy of EBV. In this
      study, we predicted six HLA-A2 restricted CTL candidate epitopes of LMP2A by
      SYFPEITHI, NetMHC and MHCPred methods combined with the polynomial method.
      Subsequently, biological functions of these peptides were tested by experiments
      in vitro. In ELISPOT assay, the positive response of the LMP2A specific CTL
      stimulated by three (LMP2A(264-272), LMP2A(426-434) and LMP2A(356-364)) of six
      peptides respectively showed that the numbers of spots forming cells (SFC) ranged
      from 55.7 to 80.6 SFC/50,000 CD8(+) T cells and the responding index (RI) ranged
      from 5.4 to 7. These three epitope-specific CTLs could effectively kill specific
      HLA-A2-expressing target cells. As a result, LMP2A(264-272) (QLSPLLGAV),
      LMP2A(426-434) (CLGGLLTMV) and LMP2A(356-364) (FLYALALLL) were identified as
      LMP2A-specific CD8(+) T-cell epitopes. It would be useful to clarify immune
      response toward EBV and to develop a vaccine against EBV-correlative NPC.

PMID- 19403059
TI  - Analysis of the conservation of T cell receptor alpha and beta chain variable
      regions gene in pp65 peptide-specific HLA-A*0201-restricted CD8+ T cells.
AB  - Many viral epitope specific T cell receptors (TCRs) in MHC-matched individuals
      have been demonstrated to involve conserved amino acid motifs in beta chain
      complementarity-determining region 3 (CDR3). However, it is not sure whether the
      conserved motifs can also be found in TCR beta chain. In previous studies, we
      developed a modified method to enlarge the percentage of cytomegalovirus (CMV)
      pp65 peptide-specific CD8(+) T cells in PBMC by continuous peptide stimulation in
      vitro, which provides sufficient number of specific T cells for detection. In
      this study, we further analyzed the restrictive usage of TCR V alpha and V beta
      gene families and investigated the CDR3 gene sequence of pp65 peptide-specific
      CD8(+) T cells. Analysis of CDR3 spectratypes suggested a restricted usage of TCR
      alpha chain AV8, AV12, AV21, AV31 families and TCR beta chain BV3, BV14, BV21,
      BV23, BV11 families in donor CD8(+) T cells stimulated by pp65 peptide. The
      sequences of these T cells involved similar sequence (TX) G (X) A in CDR3 region
      of TCR alpha chain and L (XT) G (X) A in TCR beta chain.

PMID- 19403060
TI  - Acute morphine administration reduces cell-mediated immunity and induces
      reactivation of latent herpes simplex virus type 1 in BALB/c mice.
AB  - Acute morphine administration is known to alter the course of herpes simplex
      virus infection. In this study, the effect of acute morphine administration on
      the reactivation of latent herpes was investigated in a mouse model. Because of
      the important role of cytolytic T lymphocyte (CTL) activity in the inhibition of
      herpes simplex virus type 1 (HSV-1) reactivation, the effect of acute morphine
      administration on CTL responses was also evaluated. Furthermore, lymphocyte
      proliferation and IFN-gamma production were evaluated for their roles in the
      induction of the CTL response. The findings showed that acute morphine
      administration significantly reduced CTL responses, lymphocyte proliferation, and
      IFN-gamma production. Furthermore, acute morphine administration has been shown
      to reactivate latent HSV-1. Previous studies have shown that cellular immune
      responses have important roles in the inhibition of HSV reactivation. These
      findings suggest that suppression of a portion of the cellular immune response
      after acute morphine administration may constitute one part of the mechanism that
      induces HSV reactivation.

PMID- 19403061
TI  - Construction of soluble Mamu-b*1703, a class I major histocompatibility complex
      of Chinese rhesus macaques, monomer and tetramer loaded with a simian
      immunodeficiency virus peptide.
AB  - Chinese-descent rhesus macaques have become more prevalent for HIV infection and
      vaccine investigation than Indian-origin macaques. Most of the currently
      available data and reagents such as major histocompatibility complex (MHC) class
      I tetramers, however, were derived from Indian-origin macaques due to the
      dominant use of these animals in history. Although there are significant
      differences in the immunogenetic background between the two macaque populations,
      they share a few of common MHC class I alleles. We reported in this study the
      procedure for preparation of a soluble Mamu-B*1703 (a MHC class I molecule of
      Chinese macaques) monomer and tetramer loaded with a dominant simian
      immunodeficiency virus (SIV) epitope IW9 (IRYPKTFGW) that was identified to be
      Mamu-B*1701-restricted in Indian macaques. The DNA fragment encoding the Mamu
      B*1703 extracellular domain fused with a BirA substrate peptide (BSP) was
      amplified from a previously cloned cDNA and inserted into a prokaratic expression
      vector. In the presence of the antigenic peptide IW9 and light chain beta2
      microglobulin, the expressed heavy chain was refolded into a soluble monomer.
      After biotinylation, four monomers were polymerized as a tetramer by
      phycoerythrin-conjugated streptavidin. The tetramer, having been confirmed to
      have the right conformation, was a potential tool for investigation of antigen
      specific CD8(+) T-lymphocytes in SIV vaccine models of Chinese macaques. And our
      results also suggested that some antigenic peptides reported in Indian-origin
      macaques could be directly recruited as ligands for construction of Chinese
      macaque MHC tetramers.

PMID- 19403062
TI  - CTLA4 silencing with siRNA promotes deviation of Th1/Th2 in chronic hepatitis B
      patients.
AB  - To determine whether RNA interference (RNAi) could block cytotoxic T-lymphocyte
      antigen 4 (CTLA4) in human lymphocytes in vitro and promote IFN-gamma and IL-2
      secretions, three small interfering RNAs (siRNAs) were selected based on target
      specificity sequences of human CTLA4 and transfected into human lymphocytes of
      chronic HBV patients. As a result, the expression of human CTLA4 mRNA was
      efficiently suppressed by all the three siRNAs. Compared with negative control
      (siRNA-co), siRNA-1 inhibited the expression of CTLA4 most efficiently and was
      used in the further study. The expressions of IFN-gamma and IL-2 were upregulated
      and the level of IL-4 was almost unchanged in lymphocytes transfected with siRNA
      1 compared with the blank control. These results indicated that siRNA-1 led to
      IFN-gamma and IL-2 secretions, which is a main response of Th1/Th2. In a
      conclusion, RNAi significantly suppressed the expression of human CTLA4 mRNA in
      human lymphocytes in vitro, and could induce Th1/Th2 response. It could be a new
      therapeutic strategy for chronic HBV infection.

PMID- 19403063
TI  - Direct effects of activin A on the activation of mouse macrophage RAW264.7 cells.
AB  - Macrophages play critical roles in innate immune and acquired immune via
      secreting pro-inflammatory mediators, phagocytosing microorganisms and presenting
      antigens. Activin A, a member of transforming growth factor beta (TGF-beta)
      superfamily, is produced by macrophages and microglia cells. In this study, we
      reported a direct effect of activin A as a pro-inflammatory factor on mouse
      macrophage cell line RAW264.7 cells. Our data revealed that activin A could not
      only increase IL-1 beta and IL-6 production from RAW264.7 cells, but also promote
      pinocytic and phagocytic activities of RAW264.7 cells. In addition, activin A
      obviously up-regulated MHC II expression on the surface of RAW264.7 cells,
      whereas did not influence MHC I expression. Activin A also enhanced CD80
      expression, which is a marker of activated macrophages, but did not influence
      RAW264.7 cell proliferation. These data suggest that activin A may regulate
      primary macrophage-mediated innate and acquired immune response via promoting the
      activation of rest macrophages.

PMID- 19403064
TI  - Computational prediction of the specificities of proteasome interaction with
      antigen protein.
AB  - In the processing and presentation of antigenic peptides bound by the major
      histocompatibility complex (MHC) class I molecule, the ubiquitin-proteasome
      system of the eukaryotic cells plays an important role in proteolysis and
      degradation. The ubiquitinated protein substrate is delivered into the 26S
      proteasome to be digested and degraded. The proteasome degrading substrate is
      actually protein-protein interactions. Some researches of predicting proteasome
      cleave site rarely gave the information of the proteasome interacting with its
      substrate, and so the accuracy and reliability of these proteasome cleavage
      predictive methods still need to be improved. This paper used support vector
      machine method (SVM) to predict the proteasomal cleavage sites, and the
      predictive accuracy of the model was 82.8%. We showed analytically that the
      cleavage specificities of the cleavage sites "|" and its adjacent positions, and
      gave the information about the proteasome interacting with its substrate from our
      research results. It demonstrates that the proteasome cleaving to target protein
      is selective, but not random.

PMID- 19403065
TI  - Plasma levels of monocyte chemotactic protein 3 and beta-nerve growth factor
      increase with amnestic mild cognitive impairment.
AB  - A number of studies have investigated peripheral inflammatory indices, including
      plasma cytokines and related molecules according to subtypes of dementia, but not
      in mild cognitive impairment (MCI). In this study, we used multiplex cytokine
      assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped
      as amnestic and non-amnestic, according to cognitive features. When comparing the
      levels of plasma growth factors, chemokines and cytokines, plasma levels of
      monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (beta-NGF)
      in these two groups, they were found to be significantly higher in amnestic MCI
      patients than in non-amnestic MCI patients, after adjusting for age and gender.
      This suggests that plasma MCP-3 and beta-NGF may be useful in differentiating
      subtypes of MCI.

PMID- 19403067
TI  - Measuring general dispositions to feeling empathy and distress.
AB  - The Vicarious Experience Scale (VES) is a new measure aimed at measuring the
      disposition to feeling empathy and personal distress. In Study 1, participants
      completed the VES along with the classic measure of Interpersonal Reactivity
      Index (IRI). In Studies 2 and 3, participants observed the case of a person in
      need and subsequently reported the elicited emotions of empathy and personal
      distress; participants filled in the VES either a few minutes later (Study 2) or
      three months before the presentation of the case (Study 3). The results supported
      both the convergent validity of the VES and its capacity in a specific situation.

PMID- 19403066
TI  - Studies on the specific degranulation of mast cell sensitized by several
      allergens in vitro.
AB  - Food allergy is a major health issue worldwide. Mast cells play a very important
      role in the immediate hypersensitivity for which mast cell degranulation needs to
      be studied extensively. In this study, an approach was taken to study the
      characteristics of sensitized mast cell degranulation in vitro, which associated
      with the study of mast cells and animal models. BALB/c mice were immunized
      respectively by several food allergens, then blood and peritoneal mast cells were
      collected at different time points. A dynamic determination was carried out
      between mast cells and serumal IgE. Comparative analysis on sequential time
      points showed that there was a close coincidence between mast cell degranulation
      and IgE antibody titers in sensitized BALB/c mice. Furthermore, it is interesting
      that sensitized mast cells could implement specific degranulation against the
      challenges in vitro, but the closely tropomyosins induced mast cell degranulation
      displayed cross reactions. This is very similar to IgE resisting the allergens in
      vivo. The study disclosed some characteristics on mast cells, coming from
      sensitized BALB/c mice, degranulation in vitro.

PMID- 19403069
TI  - Error affect inoculation for a complex decision-making task.
AB  - Individuals bring knowledge, implicit theories, and goal orientations to group
      meetings. Group decisions arise out of the exchange of these orientations. This
      research explores how a trainee's exploratory and deliberate process (an
      incremental theory and learning goal orientation) impacts the effectiveness of
      individual and group decision-making processes. The effectiveness of this
      training program is compared with another program that included error affect
      inoculation (EAI). Subjects were 40 Spanish Policemen in a training course. They
      were distributed in two training conditions for an individual and group decision
      making task. In one condition, individuals received the Self-Guided Exploration
      plus Deliberation Process instructions, which emphasised exploring the options
      and testing hypotheses. In the other condition, individuals also received
      instructions based on Error Affect Inoculation (EAI), which emphasised positive
      affective reactions to errors and mistakes when making decisions. Results show
      that the quality of decisions increases when the groups share their reasoning.
      The AIE intervention promotes sharing information, flexible initial viewpoints,
      and improving the quality of group decisions. Implications and future directions
      are discussed.

PMID- 19403068
TI  - [Arousal versus threat when inducing an anxiety reaction].
AB  - Over the past years, several authors have used voluntary hyperventilation as a
      method for inducing physiological arousal and the experience of anxiety. The
      purpose of this investigation is to analyze the relationship between the process
      of arousal and the experience of anxiety. In order to induce anxiety, two tasks
      were assigned: hyperventilating and preparing a speech. General hypothesis
      tested: hyperventilation will induce a high level of physiological arousal (heart
      rate and skin conductance) with a limited experience of anxiety (subjective
      appraisal of valence, intensity, and control), whereas preparing a speech will
      generate a high level of arousal and a significant increase in the experience of
      anxiety. A sample of 89 women was divided into two groups (n=45 and n=44). After
      matching the two groups in various anxiety parameters, both tasks were carried
      out in a different order by each group in the laboratory. Results obtained
      confirm the main hypothesis and provide evidence against the use of
      hyperventilation as a technique for generating anxious experience.

PMID- 19403070
TI  - [Sweetened solution intake in albino rats: taste versus calories].
AB  - Animals display preferences for sweetened over unsweetened foods under diverse
      experimental procedures. No evidence has been provided of whether flavor or
      energetic content of sweeteners determine this preference. In this experiment,
      female and male rats were exposed to water and a solution sweetened with glucose
      (sweet taste and calories) and water and a solution sweetened with sucralose
      (sweet taste without calories). We observed that animals exposed to glucose
      solution increased the sweetened water intake gradually compared to water intake
      and animals exposed to sucralose solution maintained equal sweetened water and
      water intake. This suggests that caloric content affects the increase of intake
      of sweetened liquids. However, it is important to continue to investigate whether
      history of taste exposure modifies water-intake response.

PMID- 19403071
TI  - [Dehabituation in drug-addicts and chronic pain].
AB  - In a sample of patients under treatment for dependence disorder, the fear
      avoidance model of pain was used as a theoretical framework to investigate
      differences between patients who developed chronic pain after the abstinence
      period and those who did not. In line with the model, a set of variables involved
      in the chronification process were considered: anxiety sensitivity, experiential
      avoidance, fear of pain, coping styles, anxiety, depression, and quality of life.
      Differences in clinical and dependence-related variables were analyzed: diagnosis
      of dual pathology, polyconsumption, prescribed medication, and methadone dose. A
      group of chronic pain patients (n=63) and a pain-free group (n=58) were compared.
      MANOVA and chi2 results indicated that the chronic pain patients had been
      diagnosed with dual pathology significantly more often than the pain-free group,
      they presented higher polyconsumption, and had been prescribed higher doses of
      methadone and more medications. The chronic pain group had poorer quality of life
      and significantly higher scores in anxiety sensitivity, experiential avoidance,
      and depression. No significant differences were found in coping strategies, fear
      of pain and anxiety.

PMID- 19403072
TI  - [Assessing drug consumers' care from the user's viewpoint].
AB  - In this study, we developed a tool that allows us to assess, on a regular basis,
      the perceived quality of the assistance currently provided in the centres of
      Attention for Drug-dependent People that integrate the network of the Galician
      Plan for Drugs. Our goal is to obtain a scale with acceptable psychometric
      properties, which reflects the relevant dimensions of the service and, at the
      same time, is short and easy to apply. From the analysis of 902 interviews from
      the 17 units of Attention for Drug-Dependent People in Galicia, we obtained a
      scale of only 13 items with highly satisfactory reliability and validity. This
      scale assesses 3 main dimensions (Personnel, Access, and Facilities) and it has
      high potential at management levels, as it allows both an objective diagnosis of
      the quality of the service from the users' perspective and the identification of
      key issues for constant improvement.

PMID- 19403073
TI  - Validity of the self-report on drug use by university students: correspondence
      between self-reported use and use detected in urine.
AB  - The purpose of this work was to determine the validity of a self-report on recent
      drug use (cocaine and cannabis) in a sample of university students of both sexes
      and to explore the role of attitudes toward substance use as related to this
      report. The subjects (506) were volunteers aged 17-35 years (who received an
      economic incentive) recruited at the University of Almeria (Spain). The results
      were analyzed on the basis of correspondence between the self-report of recent
      use and a urine test. Three logistic regression analyses between self-reported
      use and attitudes toward drugs were also performed. The results show that the
      convergent validity of the self-report of drug use and the urine test is quite
      satisfactory, with percentages of agreement varying from .89 to .98 and Kappa of
      .66 and .56 for cannabis and cocaine, respectively. Sensitivity of the self
      report is 57.1% (cocaine) and 91.8% (cannabis), and specificity is 99.4%
      (cocaine) and 89.6% (cannabis). The differences found in correspondence between
      the two substances are discussed with regard to self-reported attitudes on drug
      use.

PMID- 19403074
TI  - [Influence of sociodemographic variables on coping styles, social stress, and
      sexual sensation seeking in adolescents].
AB  - The aim of this study is to analyze the influence of gender, age, and type of
      high school (public/private) on coping styles solve the problem coping style,
      reference to others coping style and non-productive coping, social stress, and
      sexual sensation seeking in adolescents. A total of 4.456 adolescents
      participated. The following measures were used: Adolescent Coping Scale, Sexual
      Sensation Seeking Scale, and the Social Stress subscale of the Behavior
      Assessment System for Children. This is a cross-sectional study that used a
      stratified random sampling considering Spanish regions and type of high school
      (public/private) to select participants. The sample is representative of the
      national level at a 95.5% confidence interval. Results showed that males had
      higher scores in sexual sensation seeking and social stress compared to females.
      Female adolescents scored higher in reference to others coping style and non
      productive coping. Compared to adolescents of public high schools, adolescents
      who attended to private high schools scored higher in solve the problem coping
      style and reference to others coping style. Associations among sexual sensation
      seeking, coping styles, social stress, and health risk behaviors in adolescents
      are discussed.

PMID- 19403075
TI  - [Risky sexual behaviour and drug use in recreational nightlife context. A gender
      perspective].
AB  - The aim of this study was to analyze the relationship between the use of alcohol
      and other drugs and sexual risk behaviour, within the weekend nightlife
      recreational context. A survey was carried out in three Spanish regions (Balearic
      Islands, Galicia, and Comunidad Valenciana) with a sample of 440 young people
      (52.3% women and 47.7% men), aged 14-25, who regularly take part in nightlife
      recreational activity. Selection of participants was made using the Respondent
      Driven Sampling (RDS) procedure. The results indicate that men had more sexual
      relations under the effects of alcohol and other drugs than did women; however,
      there were no significant differences between the sexes in the use of condoms, or
      in having had sexual relations that they regretted later on. Frequency of going
      out in the nightlife context increased the level of drug use and the probability
      of having sexual relations under the effects of substances. However, no
      relationship was found between frequency of going out in the nightlife context
      and sexual risk practices.

PMID- 19403076
TI  - Prevalence and predictors of sexual aggression in dating relationships of
      adolescents and young adults.
AB  - Dyadic influences among the diverse forms of aggression in dating relationships
      of adolescents and young adults have been reported in various studies. The goal
      of this research was to extend a dyadic model of physical aggression against
      partners to sexual aggression against partners. An urban sample of 4,052
      adolescents and young adults of both genders, between 16 and 26 years old, was
      used. The percentage of male aggressors was significantly higher than that of the
      females (35.7% vs. 14.9%) and the percentage of victimization was higher for the
      women (25.1% vs.21.7%). Sexual aggression and sexual victimization was almost
      solely psychological in nature, that is, verbal coercion. As predicted by the
      dyadic model of physical aggression in dating relationships, sexual victimization
      was best predicted by sexual aggression of the individuals in this study both for
      males and females.

PMID- 19403077
TI  - [Creation and validation of a forensic protocol to assess psychological harm in
      battered women].
AB  - Psychological harm is one of the sequela of the victimization of a crime.
      Nevertheless, a diagnosis of psychological harm, that is, posttraumatic stress
      disorder (PTSD), does not constitute sufficient evidence alone given that, in
      legal terms, faking or false testimony must be detected and eliminated before an
      expert testimony can be admitted. To assess the aptitudes and strategies for
      faking psychological harm associated with domestic violence, 101 women were asked
      to fake psychological harm using the MMPI-2 and a forensic clinical interview.
      The results showed that most women (84.2%) were capable of faking in MMPI-2. The
      original validity scales of the MMPI-2 and their configurations were effective
      for the detection of faking though with a wide margin of error was observed. In
      the forensic clinical interview, it was much more difficult to simulate since
      only 3 malingerers, in which protocols were not observed any feigning strategy,
      were capable of simulating the psychological injury linked to domestic violence.
      Consequently, a multimethod approach (MMPI and interview) was contrasted and
      observed to classify correctly all subjects. Thus, a protocol for forensic
      assessment of the psychological harm consequence of domestic violence against
      women was formulated.

PMID- 19403078
TI  - [Domestic violence: a bibliographic and bibliometric review].
AB  - Violence among relatives and emotionally linked people has recently made a huge
      social impact. Professionals have suggested diverse concepts to explain the
      issue, but they have not yet reached an agreement about these concepts. The
      present work focuses on the scientific yield associated with the keywords
      "Domestic Violence", perhaps the most commonly used to refer to violence in
      romantic couples. A series of related publications is analyzed and data about
      publication years, countries, languages, sample genders, age groups, most
      prolific journals and authors, and victim-abuser relationships is provided, along
      with a reflection upon the correctness of the usage of the keyword.

PMID- 19403079
TI  - [Cognitive-behavioral intervention in menopausal symptomatology: short-term
      effects].
AB  - For a high percentage of women, menopause is associated with an important variety
      of physical, psychological, and social symptoms, susceptible to treatment by
      means of cognitive-behavioral techniques. In the present work, 28 women followed
      a group intervention (eight weekly sessions, two hours each, including
      relaxation, cognitive techniques, exercise, and diet). Results show a significant
      reduction of most of the associated symptoms (physical and psychological), and an
      increase in quality of life in the treatment group, compared to baseline and to
      the control group.

PMID- 19403080
TI  - [Assortative mating in temperament and intelligence, and the role of marital
      satisfaction].
AB  - Assortative mating is the mating of pairs that are more similar in some trait
      than would be expected from random mating. It takes place when sexually
      reproducing organisms tend to mate with individuals that are like themselves in
      some respect (positive assortative mating) or dissimilar (negative assortative
      mating). The present study measures verbal and nonverbal intelligence, along with
      several temperamental traits, testing the similarity, complementarity, social
      homogamy, and convergence hypotheses. The role of marital satisfaction was also
      analyzed. The sample comprised 357 adults (age range 19-69), who completed verbal
      aptitude, inductive reasoning, and temperament tests. The findings show that
      couples are similar in almost all the measured traits, even after controlling for
      age and educational level. Differences were observed in the couples' degree of
      similarity depending on the duration of their relationship. Further, only
      similarity in verbal intelligence for males and in impulsivity for females was
      associated with marital satisfaction in long-term couples.

PMID- 19403081
TI  - [Why and with what intention did they do it? Parents' and adolescents'
      attributions about family conflicts].
AB  - Causal (locus, stability, and controllability) and intentional (positive,
      negative, and neutral) attributions about family conflict situations reported by
      father, mother, and adolescent were studied in a sample of 270 two-parent
      families according to the type of conflict (upsetting to adolescent or upsetting
      to parents). The relationships between attributions and use of strategies in
      conflict resolution (negotiation, dominance, and indifference) were also
      examined. Results indicated that, as compared to adolescents, parents blamed
      themselves less for the conflict and perceived it as less controllable, whereas
      adolescents (especially girls) perceived a more benevolent intention than parents
      (especially mothers). Transmission of the attributional pattern via father-son
      and father/mother-daughter was observed with a clear intentional structure only
      for daughters. The attributional pattern of the triad also varied according to
      the actor-observer bias. Lastly, moderate relations were obtained between
      intentionality and use of strategies of dominance and indifference in adolescents
      and use of the three strategies in parents (especially mothers), modulated by the
      type of conflict in all the cases.

PMID- 19403082
TI  - [Social participation processes, task-oriented participation and learning as
      antecedents of group cohesion. A longitudinal perspective].
AB  - The aim of this paper is to analyze the effect of changes in social participation
      and task- and learning-oriented processes on the development of cohesion (social
      and task-focused) in new groups. Cohesion has been considered one of the most
      important constructs in small groups, and its influence on team performance and
      efficacy has been highlighted. However, there are few papers that analyze the
      processes and the variables that precede the construct and that affect its
      evolution. Results of the longitudinal study show the importance of changes in
      participation processes on the development of task cohesion and social cohesion.

PMID- 19403083
TI  - [Bridge employment and retirees' personal well-being. A structural equation model
      with a European probabilistic sample].
AB  - The aim of this paper is twofold: first, to examine the relationships between
      antecedents and consequences of bridge employment activity; second, to analyze
      the mediator role both of quality and quantity of bridge employment activities in
      the relationship between antecedents and consequences. First wave panel data from
      the SHARE (Survey of Health, Ageing and Retirement in Europe) were obtained from
      1190 men and women in Europe, using structured interviews and questionnaires.
      Structural equation modeling analyses, including the sample without missing
      values (N=650), showed that both quantity and quality of bridge employment
      participation are predictors of job satisfaction, life satisfaction, and quality
      of life in retirement. These results validate and expand the previous research on
      bridge employment activities and partial retirement.

PMID- 19403084
TI  - [Workplace bullying: prevalence and descriptive analysis in a multi-occupational
      sample].
AB  - The aim of this paper is to analyze the prevalence of mobbing in the workplace,
      as well as the main associated characteristics, in a multi-occupational sample of
      2861 workers from diverse work sectors. For this purpose, a specific mobbing
      instrument, the "Negative Acts Questionnaire--Revised" (NAQ-R) and a
      questionnaire elaborated ad hoc about sociodemographic and work aspects
      considered of interest in this study were employed. The results of this study
      provide psychometric support for the use of the Spanish version of the NAQ-R as a
      reliable and valid instrument to assess diverse levels of workplace bullying. The
      results of the study indicate that 14% of the participants had suffered mobbing
      behaviors during the past six months. Likewise, the mobbing characteristics found
      were, in general, similar to those found in diverse studies, both at national and
      international levels.

PMID- 19403085
TI  - [Spanish drivers' valuation of the penalty point system].
AB  - A key issue for the good performance of the penalty point system is that drivers
      achieve a proper understanding of its philosophy and objectives. If this
      enforcement system is valuated as an effective and socially beneficial measure,
      there is a higher probability that drivers will show a stronger and permanent
      change. On the contrary, if the penalty point system is perceived as a tax
      collecting measure, it would be very difficult for its principal aims to be
      achieved. From a national telephone survey conducted on a sample of 2.014
      respondents, the present study analyses drivers' appraisal of the Spanish penalty
      point system. The results show that drivers' evaluation of the system is very
      positive and also that they have high expectations for its success. Moreover,
      beyond a mere repressive or tax-collecting view of the penalty point system,
      drivers state that its main goal is to increase awareness and improve road
      safety.

PMID- 19403086
TI  - [Consequences of the error in bibliographical references. The specific case of
      the journal Psicothema].
AB  - The errors, as they appear in the databases of the Web of Science, found in the
      bibliographical citations of the works published in Psicothema were analyzed. The
      most frequent error found is citing the title of the journal as Psicothema,
      instead of Psicothema. The authors reveal the need to take more care when
      reviewing the titles of journals in the bibliographical references of the works.
      Such errors often prevent locating the works cited in the article. They also
      hinder authors' evaluation of the works and the journals because many
      bibliometric indicators used to establish the rankings of the best journals of a
      specialty are calculated based on the number of citations of works published in
      the journals.

PMID- 19403087
TI  - [Ranking 2008 of research productivity in Spanish public universities].
AB  - The aim of this study is to analyze research scientific productivity of Spanish
      public universities by means of using criteria related to research assessment in
      Spain. Firstly, a study to establish the weight of the indicators was developed.
      A representative sample of 1,341 university teachers participated in this study.
      Of them, 68% are senior lecturers and 32% are professors. A stratified random
      sampling procedure within each area of knowledge was used. The sample is
      representative with a 97% confidence interval. Secondly, the scientific
      productivity according to the size of university in each indicator was analyzed.
      Finally, the scientific productivity according to size of university and weight
      of each indicator was weighted. Results of the survey make possible to get a
      specific ranking in each criterion: Doctoral dissertations, Research
      projects+development, Grants for training university teachers, Articles included
      in JCR, Research periods and Doctorate programs with Quality Mention, as well as
      a global ranking. Results allow analyzing strengths and weakness of each
      university according each criterion.

PMID- 19403088
TI  - Comparison of methods for controlling maximum exposure rates in computerized
      adaptive testing.
AB  - This paper has two objectives: (a) to provide a clear description of three
      methods for controlling the maximum exposure rate in computerized adaptive
      testing -the Symson-Hetter method, the restricted method, and the item
      eligibility method- showing how all three can be interpreted as methods for
      constructing the variable sub-bank of items from which each examinee receives the
      items in his or her test; (b) to indicate the theoretical and empirical
      limitations of each method and to compare their performance. With the three
      methods, we obtained basically indistinguishable results in overlap rate and RMSE
      (differences in the third decimal place). The restricted method is the best
      method for controlling exposure rate, followed by the item-eligibility method.
      The worst method is the Sympson-Hetter method. The restricted method presents
      problems of sequential overlap rate. Our advice is to use the item-eligibility
      method, as it saves time and satisfies the goals of restricting maximum exposure.

PMID- 19403089
TI  - [Implementing graphical and analytical procedures for developing parallel tests].
AB  - We present an instrumental study in which two general procedures (graphical and
      objective) for constructing parallel forms are implemented. Both procedures are
      based on an item pool which is calibrated by means of the classical test theory.
      The graphic procedure is Gulliksen's matched random subtests method. The
      objective procedure is based on the criteria proposed by van der Linden and
      Boekkooi-Timminga, and uses zero-one programming. The stand-alone program FOR-PAR
      is free and user-friendly, and allows the parallel forms to be obtained directly
      from the item scores. FOR-PAR covers an important need in applied research,
      because developing parallel forms is a requirement in some applications, and, so
      far, no programmes of this type were available. The procedures which are
      implemented were applied in an illustrative example based on an adjustment test
      intended for visually handicapped people.

PMID- 19403090
TI  - Evaluation of five guidelines for option development in multiple-choice item
      writing.
AB  - This paper evaluates certain guidelines for writing multiple-choice test items.
      The analysis of the responses of 5013 subjects to 630 items from 21 university
      classroom achievement tests suggests that an option should not differ in terms of
      heterogeneous content because such error has a slight but harmful effect on item
      discrimination. This also occurs with the "None of the above" option when it is
      the correct one. In contrast, results do not show the supposedly negative effects
      of a different-length option, the use of specific determiners, or the use of the
      "All of the above" option, which not only decreases difficulty but also improves
      discrimination when it is the correct option.

PMID- 19403092
TI  - Remission as the "gold standard" of treatment for depression with and without
      physical symptoms.
AB  - Remission is considered the goal of depression treatment. However, painful
      physical symptoms can impair patients' functioning and impede depression
      remission. Understanding the synergic relationship between painful physical
      symptoms and depression is the first step in comprehensively treating patients
      with these conditions and helping them to achieve remission from depression.

PMID- 19403091
TI  - [Psychometric properties of the Spanish version of the Survey Work-Home
      Interaction Nijmegen (SWING)].
AB  - The aim of this work was to analyze the psychometric properties of the Spanish
      version of the "Survey Work-Home Interaction Nijmegen" (SWING) developed by S.
      Geurts and colleagues to evaluate the relationships between work and family. Its
      psychometric properties were analyzed with data from a sample of 283 emergency
      professionals. Results of confirmatory factor analyses indicated that the four
      factor model, in which both kinds of positive and negative interactions were not
      correlated, provided the best fit to the data (GFI=0.98, AGFI=0.98, NFI=0.97,
      RMR=0.03). Thus, this version maintains the original structure of 22 items
      distributed in four factors: negative work-home interaction, negative home-work
      interaction, positive work-home interaction and positive home-work interaction.
      Reliability analysis showed good internal consistency for this Spanish version
      with Cronbach alpha coefficients for the factors ranging from .77 to .89.
      Significant correlations were found between the SWING and various scales related
      to work, family, and well-being, which provided evidence of convergent validity.
      Thus, this version shows adequate psychometric properties. Guidelines are also
      provided for the use of the Spanish version of the SWING in future
      investigations.

PMID- 19403093
TI  - Effective agents in treating mania.
AB  - Numerous studies have been conducted on the efficacy of pharmaceutical agents for
      bipolar mania since the American Psychiatric Association last revised its
      guidelines for the treatment of patients with bipolar disorder. Meta-analyses of
      the available data show that, of the medications that are efficacious, rates of
      efficacy are similar, but side effects vary. When determining which drug is best
      for individual patients, clinicians must consider safety and tolerability in
      addition to efficacy.

PMID- 19403094
TI  - Diagnostic assessment of major depressive disorder.
AB  - Major depressive disorder (MDD) is a prevalent disorder that is also highly
      comorbid with other psychiatric and medical conditions. After diagnosing a major
      depressive episode, clinicians should screen for suicide risk to establish
      patient safety. Once the patient is in the appropriate treatment setting,
      clinicians should evaluate the patient for MDD by assessing the differential
      diagnosis, accompanying symptoms, psychiatric and medical comorbidities, and
      sociodemographic factors. Proper assessment of patients with MDD can lead to
      targeted treatment and a better chance of remission.

PMID- 19403095
TI  - Pain and the brain: chronic widespread pain.
AB  - Chronic widespread pain is associated with several medical and psychiatric
      disorders including, but not limited to, chronic fatigue syndrome, fibromyalgia,
      mood disorders, hepatitis, endocrine disorders such as hypothyroidism, and
      rheumatologic disorders such as rheumatoid arthritis. Careful and comprehensive
      differential diagnosis must be performed to ensure a correct diagnosis before an
      appropriate treatment can be selected. Fibromyalgia, in particular, is
      challenging to diagnose and treat because it shares many characteristics with
      other disorders and is commonly concurrent with major mood disorders. A
      comprehensive disease management strategy including patient education,
      pharmacotherapy, cognitive-behavioral therapy, and aerobic and other forms of
      exercise can be beneficial for many patients with fibromyalgia.

PMID- 19403096
TI  - Closing the efficacy-effectiveness gap: translating both the what and the how
      from randomized controlled trials to clinical practice.

PMID- 19403097
TI  - Grumpy old men (and women): mere hassle or meaningful clinical evidence?

PMID- 19403098
TI  - A roadmap to key pharmacologic principles in using antipsychotics: application in
      clinical practice.

PMID- 19403099
TI  - Venlafaxine-induced complex visual hallucinations in a 17-year-old boy.

PMID- 19403101
TI  - Reliability, not overdiagnosis.

PMID- 19403102
TI  - Use of risperidone long-acting injection to support treatment adherence and mood
      stabilization in pediatric bipolar patients: a case series.

PMID- 19403104
TI  - Effect of alkyl alcohols on partially unfolded state of proteinase K:
      Differential stability of alpha-helix and beta-sheet rich regions of the enzyme.
AB  - Proteinase K (E.C. 3.4.21.64), a serine proteinase from fungus Tritirachium
      album, has been used as a model system to investigate the conformational changes
      induced by monohydric alcohols at low pH. Proteinase K belongs to alpha/beta
      class of proteins and maintains structural integrity in the range of pH 7.0-3.0.
      Enzyme acquires partially unfolded conformation (U(P)) at pH 2.5 with lower
      activity, partial loss of tertiary structure and exposure of some hydrophobic
      patches. Proteinase K in stressed state at pH 2.5 is chosen and the
      conformational changes induced by alkyl alcohols (methanol/ethanol/isopropanol)
      are studied. At critical concentration of alcohol, conformational switch occurs
      in the protein structure from alpha/beta to beta-sheet driving the protein into O
      state. Complete loss of tertiary contacts and proteolytic activity in O-sate
      emphasize the involvement of alpha regions in maintaining the active site of the
      enzyme. Moreover, isopropanol induced unfolding of proteinase K in U(P) state
      occurred in two steps with the formation of beta state at low alcohol
      concentration followed by stabilization of beta state at high alcohol
      concentration. GuHCl and temperature induced unfolding of proteinase K in O-state
      (in 50% isopropanol) is non-cooperative as the transition curves are biphasic.
      This suggests that the structure of proteinase K in O-state has melted alpha
      regions and stabilized beta regions and that these differentially stabilized
      regions unfold sequentially. Further, the O-state of proteinase K can be attained
      from complete unfolded protein by the addition of 50% isopropanol. Hence the
      alcohol-induced O-state is different from native state or completely unfolded
      state and shows characteristics of the molten globule-like state. Thus, this
      state may be functioning as an intermediary in the folding pathway of proteinase
      K.

PMID- 19403103
TI  - Intrahepatic bile ducts develop according to a new mode of tubulogenesis
      regulated by the transcription factor SOX9.
AB  - BACKGROUND & AIMS: A number of diseases are characterized by defective formation
      of the intrahepatic bile ducts. In the embryo, hepatoblasts differentiate to
      cholangiocytes, which give rise to the bile ducts. Here, we investigated duct
      development in mouse liver and characterized the role of the SRY-related HMG box
      transcription factor 9 (SOX9). METHODS: We identified SOX9 as a new biliary
      marker and used it in immunostaining experiments to characterize bile duct
      morphogenesis. The expression of growth factors was determined by in situ
      hybridization and immunostaining, and their role was studied on cultured
      hepatoblasts. SOX9 function was investigated by phenotyping mice with a liver
      specific inactivation of Sox9. RESULTS: Biliary tubulogenesis started with
      formation of asymmetrical ductal structures, lined on the portal side by
      cholangiocytes and on the parenchymal side by hepatoblasts. When the ducts grew
      from the hilum to the periphery, the hepatoblasts lining the asymmetrical
      structures differentiated to cholangiocytes, thereby allowing formation of
      symmetrical ducts lined only by cholangiocytes. We also provide evidence that
      transforming growth factor-beta promotes differentiation of the hepatoblasts
      lining the asymmetrical structures. In the absence of SOX9, the maturation of
      asymmetrical structures into symmetrical ducts was delayed. This was associated
      with abnormal expression of CCAAT/Enhancer Binding Protein alpha and Homolog of
      Hairy/Enhancer of Split-1, as well as of the transforming growth factor-beta
      receptor type II, which are regulators of biliary development. CONCLUSIONS: Our
      results suggest that biliary development proceeds according to a new mode of
      tubulogenesis characterized by transient asymmetry and whose timing is controlled
      by SOX9.

PMID- 19403105
TI  - Multilocus sequence analysis of Brazilian Rhizobium microsymbionts of common bean
      (Phaseolus vulgaris L.) reveals unexpected taxonomic diversity.
AB  - The diazotrophic bacteria collectively known as "rhizobia" are important for
      establishing symbiotic N(2)-fixing associations with many legumes. These microbes
      have been used for over a century as an environmentally beneficial and cost
      effective means of ensuring acceptable yields of agricultural legumes. The most
      widely used phylogenetic marker for identification and classification of rhizobia
      has been the 16S rRNA gene; however, this marker fails to discriminate some
      closely related species. In this study, we established the first multilocus
      sequence analysis (MLSA) scheme for the identification and classification of
      rhizobial microsymbionts of common bean (Phaseolus vulgaris L.). We analyzed 12
      Brazilian strains representative of a collection of over 850 isolates in addition
      to type and reference rhizobial strains, by sequencing recA, dnaK, gltA, glnII
      and rpoA genes. Gene sequence similarities among the five type/reference
      Rhizobium strains which are symbionts of common bean ranged from 95 to 100% for
      16S rRNA, and from 83 to 99% for the other five genes. Rhizobial species
      described as symbionts of common bean also formed separate groups upon analysis
      of single and concatenated gene sequences, and clusters formed in each tree were
      in good mutual agreement. The five additional loci may thus be considered useful
      markers of the genus Rhizobium; in addition, MLSA also revealed broad genetic
      diversity among strains classified as Rhizobium tropici, providing evidence of
      new species.

PMID- 19403106
TI  - Physiological proteomics and stress/starvation responses in Bacillus subtilis and
      Staphylococcus aureus.
AB  - Gel-based proteomics is a useful approach for visualizing the responses of
      bacteria to stress and starvation stimuli. In order to face stress/starvation,
      bacteria have developed very complicated gene expression networks. A proteomic
      view of stress/starvation responses, however, is only a starting point which
      should promote follow-up studies aimed at the comprehensive description of single
      regulons, their signal transduction pathways on the one hand, and their adaptive
      functions on the other, and finally their integration into complex gene
      expression networks. This "road map of physiological proteomics" will be
      demonstrated for the general stress regulon controlled by sigma(B) in Bacillus
      subtilis and the oxygen starvation response with Rex as a master regulator in
      Staphylococcus aureus.

PMID- 19403107
TI  - From theory to implementation: building a multidimensional space for face
      recognition.
AB  - The purpose of the present study was to empirically construct a multidimensional
      model of face space based upon Valentine's [Valentine, T. (1991). A unified
      account of the effects of distinctiveness, inversion, and race in face
      recognition. Quarterly Journal of Experimental Psychology, 43A, 161-204;
      Valentine, T. (2001). Face-space models of face recognition. In M. J. Wenger, &
      J. T. Townsend, (Eds.). Computational, geometric, and process perspectives on
      facial cognition: Contexts and challenges. Scientific psychology series (pp. 83
      113). Mahwah, NJ: Erlbaum] metaphoric model. Two-hundred and ten participants
      ranked 200 faces on a 21-dimensional space composed of internal facial features.
      On the basis of these dimensions an index of distance from the center of the
      dimensional space was calculated. A factor analysis revealed six factors which
      highlighted the importance of both featural and holistic processes in face
      recognition. Testing the model in relation to facial distinctiveness and face
      recognition strengthened its validity by emphasizing the relevance of the
      constructed multidimensional space for face recognition. The data are discussed
      within the framework of theoretical models of face recognition.

PMID- 19403108
TI  - The effect of visual context on the identification of ambiguous environmental
      sounds.
AB  - The influence of the specificity of the visual context on the identification of
      environmental sounds (i.e., product sounds) was investigated. Two different
      visual context types (i.e., scene and object contexts)-which varied in the
      specificity of the semantic information-and a control condition (meaningless
      images) were employed. A contextual priming paradigm was used. Identification
      accuracy and response times were determined in two context conditions and one
      control condition. The results suggest that visual context has a positive effect
      on sound identification. In addition, two types of product sounds (location
      specific and event-specific sounds) were observed which exhibited different
      sensitivities to scene and object contexts. Furthermore, the results suggest that
      conceptual interactions exist between an object and a context that do not share
      the same perceptual domain. Therefore, context should be regarded as a network of
      conceptually associated items in memory.

PMID- 19403109
TI  - Acanthamoeba keratitis associated with contact lens wear in Singapore.
AB  - PURPOSE: To describe an outbreak of Acanthamoeba keratitis (AK) cases among
      contact lens wearers. DESIGN: Retrospective cohort study. METHODS: Patients with
      AK were included. Relevant demographic and clinical data were obtained from case
      records, and patients were interviewed using a standardized questionnaire.
      Contact lens practices, including type of contact lens and solution used, were
      noted. In addition, clinical features at presentation, management, and clinical
      outcomes were recorded. RESULTS: Forty-two patients (affecting 43 eyes) treated
      between 2000 and 2007 were included. Diagnosis was made by microbiologic culture
      in 35 cases and by microbiologic and histologic analysis in 2 cases, whereas the
      remainder were diagnosed based on clinical features and response to treatment.
      There was a gradual increase in cases since 2005, with a sharp increase in 2007,
      when 8 local patients were treated. Of 30 patients where contact lens solution
      data were available, 18 reported using a Complete brand Multipurpose solution
      (Advanced Medical Optics, Santa Ana, California, USA) before the infection. Among
      resident cases treated since February 2006, 7 (63%) of 11 patients used a
      Complete brand solution. Suboptimal hygiene practices were found in all patients
      interviewed. Fifteen patients required corneal grafting, with 11 undergoing
      therapeutic deep lamellar keratoplasty (DLK), 2 undergoing optical penetrating
      keratoplasty (PK), 1 undergoing optical DLK, and 1 undergoing therapeutic PK. The
      remainder were treated successfully medically with combination antiamebic
      therapy. The average duration of therapy was 116.2 days (range, 15 to 283 days).
      Of patients with radial keratoneuritis with or without epithelial disease, 83.3%
      achieved final vision of 20/40 or better, whereas this was achieved in 41.7% of
      those with ring infiltrate. Twenty-five percent of patients with ring infiltrate
      had final visual acuity of counting fingers or worse, whereas no patient with
      keratoneuritis and epithelial disease had final vision worse than counting
      fingers. CONCLUSIONS: There was an increase in the number of contact lens users
      with AK seen in the major eye departments of Singapore. Most of our patients also
      reported using a Complete brand Multipurpose solution before infection, and this
      parallels a similar outbreak in the United States. Increasing severity of
      infection was associated with worse visual outcome.

PMID- 19403110
TI  - Incidence of cystoid macular edema after cataract surgery in patients with and
      without uveitis using optical coherence tomography.
AB  - PURPOSE: To determine the incidence of cystoid macular edema (CME) after cataract
      surgery among eyes with and without uveitis using optical coherence tomography
      (OCT) and to determine risk factors for postoperative CME among eyes with
      uveitis. DESIGN: Prospective, comparative cohort study. METHODS: Single-center,
      academic practice. Forty-one eyes with uveitis and 52 eyes without uveitis
      underwent clinical examination and OCT testing within 4 weeks before cataract
      surgery and at 1-month and 3-month postoperative visits. The main outcome measure
      was incidence of CME at 1 and 3 months after surgery. RESULTS: Both uveitic and
      control eyes gained approximately 3 lines of vision (P = .6). Incidence of CME at
      1 month was 12% (5 eyes) for uveitis and 4% (2 eyes) for controls (P = .2).
      Incidence of CME at 3 months was 8% (3 eyes) for uveitis and 0% for eyes without
      uveitis (P = .08). Eyes with uveitis treated with perioperative oral
      corticosteroids had a 7-fold reduction in postoperative CME (relative risk [RR],
      0.14; P = .05). In uveitic eyes, active inflammation within 3 months before
      surgery increased the risk of CME when compared with eyes without inflammation
      (RR, 6.19; P = .04). CME was significantly associated with poorer vision (P =
      .01). CONCLUSIONS: Eyes with well-controlled uveitis may obtain similar outcomes
      to control eyes after cataract surgery (up to 3 months). Use of perioperative
      oral corticosteroids and control of uveitis for more than 3 months before surgery
      seemed to decrease the risk of postoperative CME among uveitic eyes in this
      study.

PMID- 19403111
TI  - Quantification of error in optical coherence tomography central macular thickness
      measurement in wet age-related macular degeneration.
AB  - PURPOSE: To assess error indicators encountered during optical coherence
      tomography (OCT) automated retinal thickness measurement (RTM) in neovascular age
      related macular degeneration (NVAMD) before and after bevacizumab (Avastin;
      Genentech Inc, South San Francisco, California, USA) treatment. DESIGN:
      Retrospective observational cross-sectional study. METHODS: Each of the 6 radial
      lines of a single Stratus fast macular OCT study before and 3 months following
      initiation of treatment in 46 eyes with NVAMD, for a total of 552 scans, was
      evaluated. Error frequency was analyzed relative to the presence of intraretinal,
      subretinal (SR), and subretinal pigment epithelial (SRPE) fluid. In scans with
      edge detection kernel (EDK) misplacement, manual caliper measurement of the
      central macular (CMT) and central foveal (CFT) thicknesses was performed and
      compared to the software-generated values. The frequency of the various types of
      error indicators, the risk factors for error, and the magnitude of automated RTM
      error were analyzed. RESULTS: Error indicators were found in 91.3% and 71.7% of
      eyes before and after treatment, respectively (P = .013). Suboptimal signal
      strength was the most common error indicator. EDK misplacement was the second
      most common type of error prior to treatment and the least common after treatment
      (P = .005). Eyes with SR or SRPE fluid were at the highest risk for error,
      particularly EDK misplacement (P = .039). There was a strong association between
      the software-generated and caliper-generated CMT and CFT measurements. The
      software overestimated measurements by up to 32% and underestimated them by up to
      15% in the presence of SR and SRPE fluid, respectively. CONCLUSIONS: OCT errors
      are very frequent in NVAMD. SRF is associated with the highest risk and magnitude
      of error in automated CMT and CFT measurements. Manually adjusted measurements
      may be more reliable in such eyes.

PMID- 19403112
TI  - Conjunctivochalasis and contact lenses.
AB  - PURPOSE: To assess the relationship between age and the incidence and severity of
      conjunctivochalasis in contact lens (CL) wearers by grading of
      conjunctivochalasis, and to compare the severity of conjunctivochalasis between
      CL wearers and nonwearers. DESIGN: Prospective, nonrandomized consecutive case
      study. METHODS: A total of 600 CL wearers (94 hard CLs [HCL] and 506 soft CLs
      [SCL]) aged 11 to 60 years and 579 nonwearers aged 10 to 60 years were enrolled.
      The age, gender, medical history, ocular history, and the grade and other
      parameters of conjunctivochalasis at 3 locations (nasal, middle, and temporal
      areas) were determined in all subjects. RESULTS: The prevalence of
      conjunctivochalasis increased dramatically with age in all groups. The mean grade
      of conjunctivochalasis was higher in CL wearers than in nonwearers (nasal area, P
      < .00001; temporal area, P < .00001) and was higher in HCL wearers than in SCL
      wearers (nasal area, P < .00001; temporal area, P = .00003). Parameters such as
      the downward gaze-dependent or digital pressure-dependent changes of
      conjunctivochalasis and the presence of superficial punctate keratitis all
      increased with age in both CL wearers and nonwearers. The gaze-dependent and
      pressure-dependent changes of conjunctivochalasis showed an increase with age and
      the duration of CL wear in both SCL and HCL wearers. CONCLUSIONS: This was the
      first assessment of the severity of conjunctivochalasis in a large series of
      consecutive CL wearers. Our results strongly suggest that wearing CLs is an
      important risk factor for conjunctivochalasis.

PMID- 19403113
TI  - Outcome of raised intraocular pressure in uveitic eyes with and without a
      corticosteroid-induced hypertensive response.
AB  - PURPOSE: To compare the management and outcome of raised intraocular pressure
      (IOP) in uveitis patients with a corticosteroid hypertensive response and those
      who are noncorticosteroid responders and to determine the impact of intraocular
      corticosteroid use on IOP in uveitic eyes. DESIGN: Retrospective study. METHODS:
      Eight hundred and ninety-one uveitis patients were observed in a specialized
      clinic over 3 months. The main outcome measures were frequency, characterization,
      management, and outcome of uveitis-related ocular hypertension and glaucoma.
      RESULTS: Of 891 patients with uveitis, 191 (275 eyes) had IOP elevation (21.4%).
      Of these, 95 (34.5%) eyes had glaucoma. IOP elevation attributed to
      corticosteroid-response (61.1%) was controlled more easily than that resulting
      from other causes (38.9%), requiring fewer eye drops (mean, 2.06 vs 2.52; P =
      .009) and less filtration surgery (8.9% vs 22.4%). Among eyes with uveitis and
      raised IOP, elevated IOP developed in 18 eyes (6.5%) after intravitreal
      triamcinolone, including 64.7% to 30 to 39 mm Hg and 35.3% to 40 mm Hg or more.
      Prostaglandin analogs were used in 49.2% of 246 eyes; no increase in inflammation
      was seen in these eyes. CONCLUSIONS: In this tertiary center series, most
      instances of raised IOP were attributable to corticosteroid response. Raised IOP
      induced by corticosteroid response was controlled more easily and less often
      resulted in optic nerve or visual field changes of glaucoma. Although
      intravitreous triamcinolone was associated with substantial risk of
      corticosteroid-response IOP elevation, all cases were controlled medically
      without experiencing glaucomatous injury. Prostaglandin-induced uveitis was not
      observed despite extensive use of prostaglandin IOP-lowering agents.

PMID- 19403114
TI  - Bilateral simultaneous intravitreal injections in the office setting.
AB  - PURPOSE: To report the outcomes and complications of bilateral simultaneous
      intravitreal injections performed in the office. DESIGN: Retrospective case
      series. METHODS: Records of 35 patients receiving simultaneous bilateral
      intravitreal injections between November 2007 and November 2008 were reviewed.
      Data collected included indication for injection, preinjection and postinjection
      intraocular pressure (IOP), preinjection and postinjection visual acuity (VA),
      and complications/complaints after each injection. RESULTS: A total of 208
      injections were administered to 35 patients, with a mean of 5.9 injections per
      patient (range, 2 to 14; standard deviation [SD], 3.68). One hundred and thirty
      three eyes received bevacizumab (Avastin; Genentech Inc, South San Francisco,
      California, USA) alone, 14 received bevacizumab plus preservative-free
      intravitreal triamcinolone or Triescence (Kenalog; Bristol-Myers Squibb Co, New
      York, New York, USA), 56 received ranibizumab (Lucentis; Genentech Inc), and 5
      received bevacizumab plus dexamethasone (Decadron; Merck, Whitehouse Station, New
      Jersey, USA). Mean time of postinjection follow-up was 39 days. Postinjection VA
      follow-up measurements were available for 194 injections. The indication for
      initiating therapy was choroidal neovascularization from age-related macular
      degeneration (49 eyes), diabetic macular edema (ME) (13 eyes), proliferative
      diabetic retinopathy (4 eyes), ME attributable to retinal vein occlusion (2
      eyes), and ME attributable to autoimmune retinopathy (2 eyes). The mean VA before
      each injection was 20/96 and at the next follow-up was 20/91 (P = .40). One
      patient had a painless, culture-negative endophthalmitis in 1 eye 3 days after
      bilateral bevacizumab; at 1 year VA improved from 20/400 to 20/80. CONCLUSIONS:
      Simultaneous bilateral intravitreal injections in the office are well tolerated.
      A separate povidone-iodine preparation, speculum, needle, and syringe were used
      for each eye. None of the patients requested alternating unilateral injections,
      after receiving bilateral injections. Patients should be counseled as to the risk
      of complications.

PMID- 19403115
TI  - Refractory neovascular age-related macular degeneration secondary to polypoidal
      choroidal vasculopathy.
AB  - PURPOSE: To describe a neovascular pattern associated with treatment-refractory
      neovascular age-related macular degeneration (AMD). DESIGN: A retrospective
      observational case series. METHODS:  SETTING: Clinical practice. PATIENT
      POPULATION: Twelve eyes of 12 patients with neovascular AMD in which a poor
      anatomic response to anti-vascular endothelial growth factor (VEGF) therapy was
      related to polypoidal choroidal vasculopathy (PCV). OBSERVATION PROCEDURE: Slit
      lamp biomicroscopy, optical coherence tomography, fluorescein and indocyanine
      green angiography. MAIN OUTCOME MEASURES: Snellen visual acuity (VA), anatomic
      response to therapy including presence or absence of retinal edema, hemorrhage,
      and lipid exudates. RESULTS: New or persistent PCV was identified in a cohort of
      patients demonstrating increasing macular exudation despite regular intravitreal
      ranibizumab (Lucentis; Genentech Inc, South San Francisco, California, USA) or
      bevacizumab (Avastin; Genentech Inc) injections for a minimum of 6 months.
      Treatment with verteporfin photodynamic therapy (PDT), PDT/anti-VEGF combination
      therapy, or continued anti-VEGF monotherapy resulted in complete resolution of
      exudation in 9 of 12 patients and partial resolution of exudation in the
      remaining 3 patients. CONCLUSION: Treatment-refractory neovascular AMD may harbor
      vascular abnormalities such as PCV. Modifications in therapeutic protocols may be
      indicated in order to improve visual and anatomic outcomes in this population.

PMID- 19403116
TI  - Two-month effects of individualized exercise training with or without caloric
      restriction on plasma adipocytokine levels in obese female adolescents.
AB  - OBJECTIVES: To examine if, in young obese patients, an individualized training
      programme in association with a caloric restriction programme which had an effect
      on whole-body lipid oxidation, was able to induce changes on plasma adipocytokine
      concentrations. MATERIALS AND METHODS: Twenty-seven obese female adolescents
      participated in the study. Whole-body lipid oxidation during exercise was
      assessed by indirect calorimetry during a graded cycle ergometer test. Body mass
      (BM), body mass index (BMI), percentage of body fat (%BF), insulin homeostasis
      model assessment (HOMA-IR) and fasting levels of circulating adipocytokines were
      assessed prior and after a two-month diet programme, individualized training
      programme targeted at Lipox(max) corresponded to the power at which the highest
      rate of lipids was oxidized and combined diet/training programme. RESULTS: The
      diet/training programme induced both a shift to a higher-power intensity of
      Lipox(max) (+27.8 + or - 5.1 W; p<0.01) and an increase of lipid oxidation at
      Lipox(max) (+96.8 + or - 16.2mg/min; p<0.01). The enhancement in lipid oxidation
      was significantly (p<0.01) correlated with the diet/training-induced improvement
      in %BF (r = -0.47), HOMA-IR (r = -0.66), leptin (r = -0.41), TNF-alpha (r = 
      0.48), IL-6 (r = -0.38), adiponectin (r = 0.43) and resistin (r = 0.51).
      CONCLUSION: This study showed that in obese female adolescents a moderate
      training protocol targeted at Lipox(max) and combined with a diet programme
      improved their ability to oxidize lipids during exercise, and that this
      improvement was associated with changes in plasma adipocytokine concentrations.

PMID- 19403117
TI  - [Retro- and parapharyngeal abscess in children: predictive factors of medical
      treatment failure].
AB  - OBJECTIVE: To consider the predictive factors of failure after medical treatment
      (intravenous antibiotics) first initiated in children with retro- and
      parapharyngeal abscess, without life-threatening complications. PATIENTS AND
      METHODS: Retrospective study between 1998 and 2006 of 45 children treated at the
      Nantes University Hospital for a retro- and parapharyngeal abscess. RESULTS:
      Median age was 3.8 years. Thirty (66%) patients required surgical management.
      Significant predictive factors of failure of initial medical therapy were:
      patients under 3 years of age, symptoms more than 3 days before intravenous
      antibiotic therapy, leukocyte count higher than 22,000 per millimeter cube,
      hypodensity diameter greater than 20mm, and abscess demonstrated on CT scan.
      Previous antibiotic therapy at home was not significantly related to medical
      treatment failure. Broad-spectrum antibiotic therapy associations did not improve
      medical outcome. CONCLUSION: The predictive factors of failure after initial
      medical therapy for retro- and/or parapharyngeal abscess in children are
      underlined; these factors help determine the clinical approach.

PMID- 19403118
TI  - Acute psychological stress reduces working memory-related activity in the
      dorsolateral prefrontal cortex.
AB  - BACKGROUND: Acute psychological stress impairs higher-order cognitive function
      such as working memory (WM). Similar impairments are seen in various psychiatric
      disorders that are associated with higher susceptibility to stress and with
      prefrontal cortical dysfunctions, suggesting that acute stress may play a
      potential role in such dysfunctions. However, it remains unknown whether acute
      stress has immediate effects on WM-related prefrontal activity. METHODS: Using
      functional magnetic resonance imaging (fMRI), we investigated neural activity of
      27 healthy female participants during a blocked WM task (numerical N-back) while
      moderate psychological stress was induced by viewing strongly aversive (vs.
      neutral) movie material together with a self-referencing instruction. To assess
      stress manipulation, autonomic and endocrine, as well as subjective, measurements
      were acquired throughout the experiment. RESULTS: Successfully induced acute
      stress resulted in significantly reduced WM-related activity in the dorsolateral
      prefrontal cortex (DLPFC), and was accompanied by less deactivation in brain
      regions that are jointly referred to as the default mode network. CONCLUSIONS:
      This study demonstrates that experimentally induced acute stress in healthy
      volunteers results in a reduction of WM-related DLPFC activity and reallocation
      of neural resources away from executive function networks. These effects may be
      explained by supraoptimal levels of catecholamines potentially in conjunction
      with elevated levels of cortisol. A similar mechanism involving acute stress as a
      mediating factor may play an important role in higher-order cognitive deficits
      and hypofrontality observed in various psychiatric disorders.

PMID- 19403119
TI  - [Intramuscular metastasis as a first clinical sign of a primary breast tumour].

PMID- 19403121
TI  - [Morgagni hernia].

PMID- 19403122
TI  - [Intestinal stenosis after closed abdominal trauma].

PMID- 19403123
TI  - [Three trocar laparoscopic hepatic adenoma resection].

PMID- 19403124
TI  - Determinants of organochlorine levels detectable in the amniotic fluid of women
      from Tenerife Island (Canary Islands, Spain).
AB  - Organochlorines (OCs) tend to accumulate in human tissues and can be measured in
      amniotic fluid (AF). The detection of OCs in AF samples reflects intrauterine
      exposure of human beings to these persistent organic pollutants. The present
      study was performed to evaluate the level of contamination of AF by OCs in 100
      pregnant women from Tenerife Island (Canary Islands, Spain). Gas
      chromatography/mass spectrometry (GC/MS) was used to identify and quantify the
      analytes, including 7 polychlorobiphenyl (PCB) congeners and 18 OC pesticides and
      metabolites. The majority of the AF samples (67%) showed some detectable OC
      residue, hexachlorobenzene (HCB) being the most frequently detected compound (66%
      of the samples) and at the highest concentration (median 0.023 ng/ml). Lindane
      was also detected in 28% of the samples. Inverse associations were found between
      previous lactation and hexachlorocyclohexane isomers (HCH) and cyclodienes in the
      group of younger women (p = 0.037 and p = 0.027, respectively). Unexpectedly,
      serum values of HCB (r = -0.414; p = 0.04), gamma-HCH (r = -0.294; p = 0.035),
      and SigmaOCs (r = -0.350; p = 0.014) were negatively related to age. Even more,
      women with detectable levels of HCH isomers were younger (33.9 +/- 4.9 years)
      than women with undetectable levels of them (36.1 +/- 4.9 years; p = 0.035). We
      conclude that approximately one in two fetuses in the Canary Islands is exposed
      to OCs in utero, and that, therefore, the exposure of young women from these
      Islands to some HCH isomers persists nowadays. Because prenatal exposure to these
      chemicals may be a causative factor in adverse health trends, further studies are
      required to enhance preventive measures.

PMID- 19403125
TI  - Polychlorinated biphenyls in Spanish adults: determinants of serum
      concentrations.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) are persistent compounds that may
      pose an environmental hazard to humans, food being the main source of exposure
      for the general population. OBJECTIVE: To measure the serum concentrations of the
      main PCBs in subjects from the general population in Spain, and to assess
      potential determinants of such concentrations. METHODS: Serum was obtained from
      blood samples of 953 subjects aged 35-64 years, residents in five Spanish regions
      (three from the North and two from the South), randomly selected from the EPIC
      Spain cohort. Blood collection took place during 1992-1996 and four PCB congeners
      (118, 138, 153 and 180) were determined by means of gas chromatography with
      electron-capture detection (GC-ECD). RESULTS: The concentration of total PCBs was
      459 ng/g lipids (or 3.1 microg/l); the corresponding figures for PCB 153 were 186
      ng/g lipids and 1.25 microg/l. Men had higher values than women, PCB levels
      increased with age, and serum concentration of PCBs was higher in northern
      regions. Body mass index (BMI) was inversely related to PCB concentrations, and
      fish intake was the dietary factor showing the greatest association with serum
      PCBs. The pattern described was similar for each congener separately.
      CONCLUSIONS: We found concentrations similar to those reported in European
      countries where blood collection was carried during the same period. Regional
      differences within Spain are not fully explained by anthropometric or dietary
      factors. The inverse association with BMI suggests that in the mid-1990s there
      was still ongoing or recent exposure to PCBs in Spain.

PMID- 19403126
TI  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome with a single septate uterus: a
      novel anomaly and description of treatment options.
AB  - OBJECTIVE: To report a rare Mayer-Rokitansky-Kuster-Hauser (MRKH) anomaly with a
      septate midline uterus and describe management options. DESIGN: Case report.
      SETTING: Major academic medical center. PATIENT(S): Two adolescent patients
      presented with pelvic pain and primary amenorrhea. Radiographic imaging showed
      evidence of a bicornuate uterus with two uterine horns, cervical hypoplasia, and
      absence of the upper vagina. INTERVENTION(S): Owing to pain, both patients
      planned laparoscopy with bilateral hemihysterectomies, but in each case
      laparoscopy showed evidence of a single midline uterus. Continuous hormone
      therapy was used to suppress pain and retrograde menstruation. MAIN OUTCOME
      MEASURE(S): Uterine preservation and future fertility management. RESULT(S):
      Given the fertility potential, the treatment plan was to continue hormone therapy
      until adulthood, when the young woman could select a treatment option for
      herself. After 2 years, one patient elected hysterectomy at age 18.5 due to
      persistent pain, while the other patient continues uterine preservation.
      CONCLUSION(S): We present two cases of a rare and uniquely described anomaly of
      MRKH with a single septate midline uterus. We recommend uterine preservation
      until the age of 18, at which point the patient may select her treatment option.
      Novel options include septal resection with subsequent assisted reproductive
      technology (ART) and cesarean delivery or ART and a gestational carrier.

PMID- 19403127
TI  - Resumption of ovarian function 20 years after chemotherapy-induced ovarian
      failure: a case report.
AB  - OBJECTIVE: To describe a case of resumption of ovarian function 20 years after
      chemotherapy-induced ovarian failure. DESIGN: Case report. SETTING: University
      teaching hospital. PATIENT(S): A 33-year-old nulliparous black woman.
      INTERVENTION(S): Progesterone challenge, transvaginal ultrasound (TVS). MAIN
      OUTCOME MEASURE(S): Estradiol and FSH hormone levels. RESULT(S): Confirmation
      that ovarian function returned in a women who presented with cyclic vaginal
      bleeding after a 20-year history of amenorrhea secondary to chemotherapy-induced
      ovarian failure. CONCLUSION(S): Return of ovarian function is possible after
      prolonged periods in women with chemotherapy-induced ovarian failure.

PMID- 19403128
TI  - Two interesting cases of ovarian pregnancy after in vitro fertilization-embryo
      transfer and its successful laparoscopic management.
AB  - OBJECTIVE: To report two interesting and rare cases of ovarian pregnancies, after
      IVF-embryo transfer, and their successful laparoscopic management. DESIGN: Case
      report. SETTING: Fertility Research Centre, G G Hospital, Chennai, India.
      PATIENT(S): Two patients with primary infertility. INTERVENTION(S): Detection of
      ovarian pregnancy. MAIN OUTCOME MEASURE(S): Early detection and successful
      laparoscopic management. RESULT(S): Pregnancy outcome following IVF-ET, early
      detection of ovarian ectopic pregnancy and successful laparoscopic management.
      CONCLUSION(S): The women who conceive after IVF-embryo transfer are at a
      significantly higher risk of ectopic pregnancy. Although ovarian ectopic
      pregnancy is a rare event, the clinician should always keep the possibility in
      mind as the condition can be easily missed.

PMID- 19403129
TI  - Spontaneous intrauterine pregnancy after unilateral placement of tubal occlusive
      microinsert.
AB  - OBJECTIVE: To present a case in which the use of a titanium/nickel microinsert in
      the management of unilateral hydrosalpinx contributed to a spontaneous
      intrauterine pregnancy. DESIGN: Case report. SETTING: University hospital.
      PATIENT(S): A 37-year-old nulligravid female with dense pelvic adhesive disease
      and unilateral hydrosalpinx. INTERVENTION(S): Unilateral proximal occlusion of
      left fallopian tube with titanium/nickel microinsert. MAIN OUTCOME MEASURE(S):
      Pregnancy. RESULT(S): Spontaneous intrauterine pregnancy after confirmation via
      hysterosalpingogram of left tubal occlusion and right tubal patency.
      CONCLUSION(S): Transcervical proximal tubal occlusion using titanium/nickel
      microinserts provides an alternative in the management of hydrosalpinx in the
      setting of tubal factor infertility. Additionally, in the setting of a unilateral
      hydrosalpinx, unilateral occlusion can contribute to spontaneous intrauterine
      pregnancy.

PMID- 19403130
TI  - Complete en bloc resection of a large ampullary adenoma with a focal
      adenocarcinoma by using endoscopic submucosal dissection (with video).

PMID- 19403131
TI  - Endoscopic submucosal dissection of large colorectal tumors by using a novel
      spring-action S-O clip for traction (with video).
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) allows en bloc resection of
      large GI neoplasms, regardless of their size; however, technical difficulties
      associated with ESD in the colorectum make it less widely applied in the
      treatment of tumors in this region. To address this difficulty, we designed a
      rubber strip-based traction device, called the S-O clip (Sakamoto-Osada clip) and
      reported previously that ESD with this device was effective for complete
      resection of large, superficial colorectal neoplasms. In this report, we describe
      a novel spring-action version of the S-O clip (spring S-O clip) that improves the
      facility of clip use during ESD of colorectal tumors. OBJECTIVE: To evaluate the
      efficacy and safety of the spring S-O clip for ESD of colorectal neoplasms.
      DESIGN: Case series. SETTING: Juntendo University Hospital. MAIN OUTCOME
      MEASUREMENTS: The efficacy and safety of the spring S-O clip traction device
      during ESD of colorectal tumors. RESULTS: In 3 cases, a large, superficial
      neoplasm in the right side of the colon was removed safely and successfully en
      bloc without complication. Procedure times for the 3 cases were 44, 27, and 49
      minutes, with resected specimens measuring 40, 24, and 35 mm, respectively.
      LIMITATION: Uncontrolled study. CONCLUSION: This limited case series demonstrates
      that spring S-O clip-assisted ESD is safe and effective for en bloc resection of
      large superficial neoplasms in the right side of the colon.

PMID- 19403132
TI  - Adaptive NN control for discrete-time pure-feedback systems with unknown control
      direction under amplitude and rate actuator constraints.
AB  - This paper focuses on the problem of adaptive neural network tracking control for
      a class of discrete-time pure-feedback systems with unknown control direction
      under amplitude and rate actuator constraints. Two novel state-feedback and
      output-feedback dynamic control laws are established where the function tanh(.)
      is employed to solve the saturation constraint problem. Implicit function theorem
      and mean value theorem are exploited to deal with non-affine variables that are
      used as actual control. Radial basis function neural networks are used to
      approximate the desired input function. Discrete Nussbaum gain is used to
      estimate the unknown sign of control gain. The uniform boundedness of all closed
      loop signals is guaranteed. The tracking error is proved to converge to a small
      residual set around the origin. A simulation example is provided to illustrate
      the effectiveness of control schemes proposed in this paper.

PMID- 19403133
TI  - Development, initial reliability and validity testing of an observational tool
      for assessing technical skills of operating room nurses.
AB  - BACKGROUND: The recent emergence of the Systems Approach to the safety and
      quality of surgical care has triggered individual and team skills training
      modules for surgeons and anaesthetists and relevant observational assessment
      tools have been developed. OBJECTIVE: To develop an observational tool that
      captures operating room (OR) nurses' technical skill and can be used for
      assessment and training. METHODS: The Imperial College Assessment of Technical
      Skills for Nurses (ICATS-N) assesses (i) gowning and gloving, (ii) setting up
      instrumentation, (iii) draping, and (iv) maintaining sterility. Three to five
      observable behaviours have been identified for each skill and are rated on 1-6
      scales. Feasibility and aspects of reliability and validity were assessed in 20
      simulation-based crisis management training modules for trainee nurses and
      doctors, carried out in a Simulated Operating Room. RESULTS: The tool was
      feasible to use in the context of simulation-based training. Satisfactory
      reliability (Cronbach alpha) was obtained across trainers' and trainees' scores
      (analysed jointly and separately). Moreover, trainer nurse's ratings of the four
      skills correlated positively, thus indicating adequate content validity.
      Trainer's and trainees' ratings did not correlate. CONCLUSIONS: Assessment of OR
      nurses' technical skill is becoming a training priority. The present evidence
      suggests that the ICATS-N could be considered for use as an assessment/training
      tool for junior OR nurses.

PMID- 19403134
TI  - A narrative review of interventions to support family carers who provide physical
      care to family members with cancer.
AB  - OBJECTIVES: Most reports of cancer caregivers' needs focus on information and
      psychosocial needs. Less is known about practical knowledge and support carers
      need to provide physical care in the home. This review aimed to identity and
      critique studies of the development and/or evaluation of interventions to enable
      family carers to provide physical/practical care to a family member with cancer.
      DESIGN: Narrative review. DATA SOURCES: Studies which included adult carers who
      provided care to a family member with cancer (any stage). Search sources included
      Psych Info., Cochrane Central Register of Controlled Trials, Embase Ovid, Embase,
      Ovid Medline, CINAHL, other databases, systematic and other reviews. REVIEW
      METHODS: All types of study designs were included. Initially, multiple and
      broadly defined search strategies and terms were used to capture the range of
      potential studies; later more refined procedures were applied. RESULTS: In total,
      19 studies were included in the review. Interventions focused on skills
      development (n=1), managing symptoms (n=9), problem solving (n=5) and learning
      (n=4). Few studies were identified with well-defined and evaluated interventions
      to assist carers to provide physical care for their family member with cancer.
      CONCLUSIONS: Future research is needed to develop well-defined interventions on
      practical skills and evaluate the outcomes for patients and caregivers.

PMID- 19403135
TI  - Identification of CELSR1 as a susceptibility gene for ischemic stroke in Japanese
      individuals by a genome-wide association study.
AB  - OBJECTIVE: We have performed a genome-wide association study (GWAS) to identify
      genetic variants that confer susceptibility to ischemic stroke. METHODS: A total
      of 6341 individuals from three independent populations was examined. Subject
      panel A comprised 131 individuals with ischemic stroke and 135 controls; subject
      panel B comprised 790 individuals with ischemic stroke and 3435 controls; and
      subject panel C comprised 71 individuals with ischemic stroke and 1779 controls.
      A GWAS for ischemic stroke was performed in subject panel A with the use of the
      GeneChip Human Mapping 500K Array Set (Affymetrix). RESULTS: The relation of 100
      single nucleotide polymorphisms (SNPs) selected by the GWAS to ischemic stroke
      was examined in 705 subjects with ischemic stroke and 3426 controls selected from
      subject panel B. Three SNPs (rs1671021 of LLGL2, rs9615362 of CELSR1, and
      rs753307 of RUVBL2) were significantly (P<0.05) associated with ischemic stroke.
      After DNA sequencing of linkage disequilibrium blocks containing these SNPs,
      three tag SNPs (rs6007897 of CELSR1, rs1671021 of LLGL2, and rs1062708 of RUVBL2)
      and a nonsynonymous SNP (rs4044210 of CELSR1) were examined for their relation to
      ischemic stroke in subject panels B and C. Both rs6007897 (A-->G, Thr2268Ala) and
      rs4044210 (A-->G, Ile2107Val) of CELSR1 as well as rs1671021 (T-->C, Phe479Leu)
      of LLGL2 were significantly associated with ischemic stroke in subject panel B.
      The rs6007897 and rs4044210 polymorphisms of CELSR1 were also significantly
      associated with ischemic stroke in subject panel C. CONCLUSION: CELSR1 is a
      susceptibility gene for ischemic stroke in Japanese individuals, although the
      functional relevance of the identified SNPs was not determined.

PMID- 19403136
TI  - Contribution of cardiovascular risk factors to coronary risk in patients with
      intermittent claudication in the PRIME Cohort Study of European men.
AB  - BACKGROUND: Intermittent claudication (IC) is associated with an increased
      cardiovascular morbidity. The goal of the present study was to assess the
      contribution of conventional cardiovascular risk factors (CVRFs) to this
      increased risk. METHOD: The PRIME Study is a multicenter Prospective Cohort Study
      of 10 602 men recruited in 1991-1993, aged 50-59 at baseline and followed over 10
      years. At baseline, a questionnaire on socio demographic data was self
      administered and CVRFs were measured. Composite outcome consisted of incident MI,
      effort angina, unstable angina and coronary death. The standardized questionnaire
      of the London School of hygiene was used to identify claudicants. Data were
      analyzed using multivariate Cox models. RESULTS: Probable and possible cases of
      IC were reported by 1.4% (135) and 4.6% (442) of subjects, respectively. Compared
      to subjects with no claudication, the probable cases demonstrated higher rates of
      CVRFs. The incidence of CAD events was 7.23/1000 person-year. Compared to non
      claudicants, probable claudicants had an increased age and country adjusted risk
      of coronary events (HR (95% CI), 2.4 (1.5-3.7), p<0.0001). After further
      adjustments for school duration, family history of early myocardial infarction,
      tobacco consumption, alcohol consumption, BMI, systolic blood pressure,
      antihypertensive treatment, diabetes, total cholesterol, HDL-cholesterol,
      triglycerides and lipid-lowering treatment, participants with probable
      claudication had an increased risk of coronary events but this was no longer
      significant (HR (95% CI), 1.3 (0.8-2.1), p=0.23). CONCLUSION: IC is associated
      with an increased risk of developing coronary events. This association is largely
      explained by the coexistence of CVRFs.

PMID- 19403137
TI  - Comparative accuracy of radiostereometric and optical tracking systems.
AB  - This study aims to quantify and compare the accuracy of traditional
      radiostereometric analysis (RSA), fluoroscopic RSA (fRSA), and optical tracking
      systems. Three phantoms were constructed, each having three stainless steel
      spheres and three reflective markers. One phantom was mounted to the base of a
      precision cross-slide table, one to the base of a precision rotation table, and
      the third was mounted to each moveable tabletop. Two dial-gauges, rigidly mounted
      to the cross-slide table and rotation table, quantified translations and
      rotations. Two fluoroscopy units placed orthogonally tracked the steel spheres
      while a four-camera optical motion capture system tracked the reflective markers
      in three-dimensional space. RSA was performed with both digital radiography and
      fluoroscopy. Three axes of translation were tested: parallel to one fluoroscopy
      image, parallel to the other fluoroscopy image, and at approximately 45 degrees
      to each image. One axis of rotation was tested. Intraclass correlation
      coefficients indicated excellent agreement between the actual (dial-gauge) and
      measured translations for all modalities (ICCs>0.99) and excellent agreement
      between actual and measured rotations for RSA and fRSA (ICCs>0.99). Standard
      errors of measurement ranged from 0.032 mm and 0.121 degrees for RSA, to 0.040 mm
      and 0.229 degrees for fRSA, and to 0.109 mm and 0.613 degrees for optical
      tracking. Differences between actual and measured translations along the 45
      degrees axis were significantly smaller than the two parallel axes. These
      findings suggest that under ideal conditions, accuracy of fRSA is comparable to
      traditional RSA, and superior to optical tracking. Accuracy is highest when
      measured at 45 degrees to the fluoroscopy units.

PMID- 19403138
TI  - Computer simulation of trabecular remodeling in human proximal femur using large
      scale voxel FE models: Approach to understanding Wolff's law.
AB  - Ever since Julius Wolff proposed the law of bone transformation in the 19th
      century, it has been widely known that the trabecular structure of cancellous
      bone adapts functionally to the loading environment. To understand the mechanism
      of Wolff's law, a three-dimensional (3D) computer simulation of trabecular
      structural changes due to surface remodeling was performed for a human proximal
      femur. A large-scale voxel finite element model was constructed to simulate the
      structural changes of individual trabeculae over the entire cancellous region. As
      a simple remodeling model that considers bone cellular activities regulated by
      the local mechanical environment, nonuniformity of local stress was assumed to
      drive the trabecular surface remodeling to seek a uniform stress state.
      Simulation results demonstrated that cell-scale ( approximately 10microm)
      remodeling in response to mechanical stimulation created complex 3D trabecular
      structures of the entire bone-scale ( approximately 10cm), as illustrated in the
      reference of Wolff. The bone remodeling reproduced the characteristic anisotropic
      structure in the coronal cross section and the isotropic structures in other
      cross sections. The principal values and axes of a structure characterized by
      fabric ellipsoids corresponded to those of the apparent stress of the structure.
      The proposed large-scale computer simulation indicates that in a complex
      mechanical environment of a hierarchical bone structure of over 10(4) length
      scale (from approximately 10microm to approximately 10cm), a simple remodeling at
      the cellular/trabecular levels creates a highly complex and functional trabecular
      structure, as characterized by bone density and orientation.

PMID- 19403139
TI  - Photosensitization of colloidal TiO2 nanoparticles with phycocyanin pigment.
AB  - Bluish phycocyanin is a water soluble pigment having strong visible light
      absorption at 615 nm. The dynamics of photoinduced electron injection from
      phycocyanin to colloidal TiO(2) nanoparticles has been studied by absorption, FT
      IR, steady state and time-resolved fluorescence spectroscopic methods. The
      phycocyanin adsorbed on the surface of colloidal TiO(2) nanoparticles, the
      apparent association constant (K(app)) for the association between colloidal
      TiO(2) nanoparticles and phycocyanin was measured from both absorption changes
      (K(app)=4.01x10(2) M(-1)) and fluorescence quenching data (K(app)=5.20x10(2) M(
      1)). The value of K(app) obtained from the data of fluorescence quenching matches
      with that determined from the absorption spectral changes. The good agreement
      between these values of K(app) highlighted the validity of assumption proposed
      for the association between phycocyanin and colloidal TiO(2) nanoparticles. The
      free energy change (DeltaG(et)) for electron injection has been calculated by
      applying Rehm-Weller equation. Electron injection from excited state phycocyanin
      into the conduction band of TiO(2) is suggested.

PMID- 19403140
TI  - Synthesis of Co(x)Pt(1-x) alloy nanoparticles of different phase by micellar
      technique and their properties study.
AB  - Among many ferromagnetic materials, CoPt alloy nanoparticles with high coercivity
      and small grain size are one of the potential candidates having its application
      in high-density storage media manufacturing. CoPt alloy nanoparticles of
      different compositions have been prepared in TX-100 micellar medium and capped
      with sodium oleate to prevent the agglomeration during annealing at high
      temperature. Their structural and magnetic properties were investigated before
      and after heat treatment. The particles with approximately 50:50 compositions of
      Co and Pt gives L1(0) phase after annealing at 900 degrees C for 1 h and show a
      high coercivity (approximately 4.4 kOe at room temperature) and remanence due to
      its highly anisotropic L1(0) structure.

PMID- 19403141
TI  - Temperature sensitivity of wormlike micelles in poly(oxyethylene) surfactant
      solution: importance of hydrophilic-group size.
AB  - We have studied the temperature sensitivity of the rheology of the wormlike
      micellar solutions formed in poly(oxyethylene) cholesteryl ether (ChEO(m), m=15
      and 30) upon addition of tri(ethyleneglycol) mono n-dodecyl ether (C(12)EO(3))
      and monolaurin. We have found that increasing the poly(oxyethylene) chain length
      of ChEO(m) greatly reduces the temperature-sensitivity of the viscosity of the
      solution. In the viscous region small changes in the cosurfactant composition can
      subtly change the temperature sensitivity depending on the temperature range and
      type of cosurfactant. For, C(12)EO(3), which is a poly(oxyethylene) surfactant,
      the temperature sensitivity is lower at lower temperatures and higher at higher
      temperatures if the cosurfactant mixing fraction is high and vice versa if the
      mixing fraction is low. For monolaurin, the temperature sensitivity increases
      with cosurfactant mixing fraction in the viscous region. In the ChEO(30)
      monolaurin system viscous solutions are not formed at any temperature that we
      studied. We have discussed these results in terms of the reduction of the average
      curvature of micellar interface with temperature due to dehydration of the
      poly(oxyethylene) chain and formation of branches in long micelles. We indicate
      the scientific and technical significance of our findings.

PMID- 19403142
TI  - Assessment of solubilization characteristics of different surfactants for
      carvedilol phosphate as a function of pH.
AB  - The effect of surfactants on the solubility of a new phosphate salt of carvedilol
      was investigated at different biorelevent pH to evaluate their solubilization
      capacity. Solutions of different classes of surfactants viz., anionic-sodium
      dodecyl sulfate (SDS) and sodium taurocholate (STC), cationic
      cetyltrimethylammonium bromide (CTAB) and non-ionic-Tween 80 (T80) were prepared
      in the concentration range of 5-35 mmol dm(-3) in buffer solutions of pH 1.2,
      3.0, 4.5, 5.8, 6.8 and 7.2. The solubility data were used to calculate the
      solubilization characteristics viz. molar solubilization capacity, water micelle
      partition coefficient, free energy of solubilization and binding constant.
      Solubility enhancement in basic pH was in following order: CTAB>T80>SDS>STC. CTAB
      and T80 showed remarkable solubility enhancement in acidic pH as well. Among the
      anionic surfactants, solubility in acidic medium was retarded except at pH 1.2 in
      case of SDS. Cationic and non-ionic surfactants were found to be suitable for
      enhancing the solubility of CP which can be employed for maintaining the in vitro
      sink condition in the basic dissolution medium. While anionic surfactants showed
      solubility retardant behavior which may be exploited in increasing the drug
      entrapment efficiency of a colloidal drug delivery system formulated by
      emulsification technique.

PMID- 19403143
TI  - Simultaneous adsorption of Cd2+ and phenol on modified N-doped carbon nanotubes:
      experimental and DFT studies.
AB  - Carbon nanotubes are novel materials that have been investigated for diverse
      applications, but only a few studies have been focused on environmental issues.
      In this work, we report on the efficient adsorption of phenol and cadmium ions on
      N-doped carbon nanotubes (CNx), which have been modified in air at different
      temperatures. The pristine and modified CNx nanotubes were characterized by SEM,
      TGA, elemental analysis and their surface areas were also determined. The
      adsorption experiments of toxic pollutants were carried out in batch reactors at
      25 degrees C. The characterization of modified CNx by these techniques showed an
      increase in oxygen content and surface area in comparison with the pristine CNx
      tubes. The individual adsorption capacity was 0.10 and 0.07 mmol/g for phenol and
      Cd(2+), respectively. The experimental data of the competitive adsorption of
      phenol and Cd(2+) revealed that the cadmium removal was favored as the phenol
      concentration increased, whereas the phenol adsorption capacity was slightly
      affected at any cadmium concentration. These results suggest that modified CNx
      tubes have a great potential in environmental applications as adsorbents of
      organic and inorganic compounds in aqueous phases. In addition, first-principles
      calculations were carried out in order to elucidate the mechanism of Cd(2+)
      adsorption on CNx.

PMID- 19403144
TI  - Experimental study and modelling of selenite sorption onto illite and smectite
      clays.
AB  - This study provides a large set of experimental selenite sorption data for pure
      smectite and illite. Similar sorption behavior existed in both clays: linear
      within a large range of the Se concentrations investigated (from 1x10(-10) to
      1x10(-3) M); and independent of ionic strength. Selenite sorption was also
      analysed in the illite/smectite system with the clays mixed in two different
      proportions, as follows: (a) 30% illite-70% smectite and (b) 43% illite-57%
      smectite. The objective of the study was to provide the simplest model possible
      to fit the experimental data, a model also capable of describing selenite
      sorption in binary illite/smectite clay systems. Selenite sorption data,
      separately obtained in the single mineral systems, were modeled using both a one-
      and a two-site non-electrostatic model that took into account the formation of
      two complexes at the edge sites of the clay. Although the use of a two-site model
      slightly improved the fit of data at a pH below 4, the simpler one-site model
      reproduced satisfactorily all the sorption data from pH 3 to 8. The complexation
      constants obtained by fitting sorption data of the individual minerals were
      incorporated into a model to predict the adsorption of selenium in the
      illite/smectite mixtures; the model's predictions were consistent with the
      experimental adsorption data.

PMID- 19403145
TI  - Evidence for increased ingestion of plastics by northern fulmars (Fulmarus
      glacialis) in the Canadian Arctic.

PMID- 19403146
TI  - Livedo racemosa as a marker of increased risk of recurrent thrombosis in patients
      with negative anti-phospholipid antibodies.
AB  - BACKGROUND AND OBJECTIVE: Livedo reticularis racemosa and cerebrovascular lesions
      characterize Sneddon's syndrome. We report 23 patients with livedo racemosa and
      describe the association with thrombotic events. Our objective was to determine
      whether livedo racemosa may be an independent clinical marker for the development
      of thrombotic events in patients who test negative for anti-phospholipid
      antibodies. METHODS: Twenty-three patients with widespread livedo racemosa were
      studied. None of the patients were positive for anti-phospholipid antibodies. The
      clinical protocol included a register of thrombotic events, fetal death or
      miscarriages, hypertension, and valvular heart disease. Cerebral MRI and
      echocardiography were systematically performed in all patients. RESULTS: Nineteen
      patients (82.60%) had thrombotic events. Fifteen (65.21%) had arterial thrombosis
      and eleven (47.82%) presented venous occlusions. Seven patients (30.43%) had both
      arterial and venous thrombosis. Fetal losses were recorded in seven cases
      (30.43%), with a total number of 33; five patients had 3 or more fetal losses.
      Eleven out of 23 patients (47.82%) had valvular heart disease. Arterial
      hypertension was detected in 16 (69.56%) patients. Four patients did not have
      thrombotic events but had other clinical manifestations. After anti-coagulation
      therapy was withdrawn, a new thrombotic event was observed in 9 out of the 14
      treated patients (64.28%). CONCLUSIONS: Livedo racemosa seems to be a good
      clinical marker for the detection of hypercoagulable states even in the absence
      of anti-phospholipid antibodies or other known biologic markers of thrombosis.
      Long-term anti-coagulation is probably warranted in patients with livedo racemosa
      and a previous thrombotic event.

PMID- 19403147
TI  - [Overview and perspective of mandibular reconstruction].

PMID- 19403148
TI  - [276 cases of horizontal infrahyoid myocutaneous flap].
AB  - INTRODUCTION: The infrahyoid myocutaneous flap was described by Wang et al. in
      1986. The horizontal design of the skin paddle is a modification of this
      technique allowing for a smaller scar. We have been systematically using this
      modified technique for 10 years. We had for aim to describe the interest of the
      horizontal infrahyoid myocutaneous flap for cervicofacial carcinology. PATIENTS
      AND METHODS: A horizontal infrahyoid myocutaneous flap procedure was performed in
      276 cervicofacial carcinology patients for lesions of the mouth floor, the
      mandibular gum, the oropharynx and the tongue between March 1997 and March 2007.
      RESULTS: No complications were observed in 252 patients. No patient presented
      with total flap necrosis. DISCUSSION: Modifying the infrahyoid myocutaneous flap
      technique with a horizontal design of the skin paddle does not modify the
      reliability of the flap and prevents more extensive scars. The main indications
      of this technique are defects of the mouth floor, the tongue and the oropharynx.

PMID- 19403150
TI  - [Address from the president for 2009].

PMID- 19403151
TI  - Identifying hepatitis C virus: endemic areas and estimating the viral antibody
      prevalence based on the prevalence of ALT elevation.
AB  - To evaluate the validity of predicting the prevalence of antibodies to hepatitis
      C virus (anti-HCV) based on the prevalence of alanine transaminase (ALT)
      elevation (>40IU/l), we conducted a community-based study. In total, 56698
      individuals underwent health examinations in 2004. Another 43738 subjects in 2005
      were the validation set. It should be valid to predict the prevalence of anti-HCV
      in villages (>25 participants) by the prevalence of ALT elevation. The equation
      was anti-HCV (%)=(% of ALT elevation - 6%)/65% (n=487 villages, R(2)=0.58).
      Villages with prevalence of ALT elevation >13% had a high probability of being
      HCV-endemic (anti-HCV >10%). The sensitivity and specificity were 73.6 and 74.6%,
      respectively. By the validation set, the positive and negative predictive values
      were 52.0% and 79.4%, respectively. Clinical and epidemiological deductions of
      the equation were that baseline of ALT elevation was 6% and two-thirds of anti
      HCV-positive subjects had elevated ALT.

PMID- 19403152
TI  - Multifrequency characterization of viscoelastic polymers and vapor sensing based
      on SAW oscillators.
AB  - Simplified relations for the changes in SAW velocity and attenuation due to thin
      polymer coatings and vapor sorption are presented by making analytic
      approximations to the complex theoretical model developed earlier by Martin et
      al. [Anal. Chem. 66 (14) (1994) 2201-2219]. The approximate velocity relation is
      accurate within 4% for the film thicknesses up to 20% of the acoustic wavelength
      in the polymer film, and is useful for analyzing the mass loading, swelling and
      viscoelastic effects in SAW vapor sensors. The approximate attenuation relation
      is accurate within 20% for very thin films, (less than 2% of the acoustic
      wavelength in the film). Based on these relations, a new procedure for
      determination of polymer viscoelastic properties is described that exploits the
      frequency dependence of the velocity and attenuation perturbations, and employs
      multifrequency measurement on the same SAW platform. Expressions for individual
      contributions from the mass loading, film swelling and viscoelastic effects in
      SAW vapor sensors are derived, and their implications for the sensor design and
      operation are discussed. Also, a new SAW comb filter design is proposed that
      offers possibility for multimode SAW oscillator operation over a decade of
      frequency variation, and illustrates feasibility for experimental realization of
      wide bandwidth multifrequency SAW platforms.

PMID- 19403153
TI  - Investigation of transmit and receive performance at the fundamental and third
      harmonic resonance frequency of a medical ultrasound transducer.
AB  - In this study, the phenomenon of higher harmonic thickness resonance of a
      piezoelectric transducer was used to investigate potentially additional
      sensitivity at the third harmonic frequency for conventional medical transducers.
      The motivation for this research is that some applications in medical ultrasound
      (e.g. third harmonic transmit phasing and contrast imaging) need probes which are
      sensitive around both the fundamental and third harmonic frequencies, and that
      these higher harmonic thickness modes, although often considered as undesired,
      might be used beneficially. The novelty aspect in this study is the presented
      transmit and receive potential at both the fundamental and third harmonic of a
      conventional cardiac probe with modified electrical tuning. Elements of an
      experimental PZT-based phased-array probe (f(c)=3 MHz, 64 elements, element
      width=0.3mm, elevation aperture=13 mm) were electrically retuned with series
      inductors around the third harmonic resonance frequency at 10 MHz. Hydrophone
      measurements with 10-MHz-tuned elements showed that, as compared to a
      conventionally tuned element, the transmit transfer function at the third
      harmonic increased more than 23 dB, while the sensitivity at the fundamental
      frequency was only 6 dB lower. Pulse-echo measurements showed that the two-way
      transfer function of a 10-MHz-tuned element resulted in 20 dB increased
      sensitivity around the third harmonic as compared to an untuned element.
      Simulated transfer functions, from both a 1D KLM and 2D finite element model of
      an element of the experimental array transducer, confirmed the measured
      sensitivity peaks at the fundamental and third harmonic. In conclusion, this
      study demonstrated the effect of changing the electrical tuning on a conventional
      array transducer which increased the sensitivity around the third harmonic
      resonance frequency, while maintaining good sensitivity at the fundamental
      frequency.

PMID- 19403154
TI  - Isolation and characterization of Solenopsis invicta virus 3, a new positive
      strand RNA virus infecting the red imported fire ant, Solenopsis invicta.
AB  - We report the discovery of a new virus from the red imported fire ant, Solenopsis
      invicta. Solenopsis invicta virus 3 (SINV-3) represents the third virus
      discovered from this ant species using the metagenomics approach. The single
      (positive)-strand RNA, monopartite, bicistronic genome of SINV-3 was sequenced in
      entirety (GenBank accession number FJ528584), comprised of 10,386 nucleotides,
      and polyadenylated at the 3' terminus. This genome size was confirmed by Northern
      analysis. The genome revealed 2 large open reading frames (ORFs) in the sense
      orientation with an untranslated region (UTR) at each end and between the two
      ORFs. The 5' proximal ORF (ORF 1) encoded a predicted protein of 299.1 kDa (2580
      amino acids). The 3' proximal ORF (ORF 2) encoded a predicted protein of 73.2 kDa
      (651 amino acids). RNA-dependent RNA polymerase (RdRp), helicase, and protease
      domains were recognized in ORF 1. SDS-PAGE separation of purified SINV-3
      particles yielded 2 bands (ostensibly capsid proteins) with a combined molecular
      mass of 77.3 kDa which was similar to the mass predicted by ORF 2 (73.2 kDa).
      Phylogenetic analysis of the conserved amino acid sequences containing domains I
      to VIII of the RdRp from dicistroviruses, iflaviruses, plant small RNA viruses,
      picornaviruses, and 4 unassigned positive-strand RNA viruses revealed a
      trichotomous phenogram with SINV-3 and Kelp fly virus comprising a unique
      cluster. Electron microscopic examination of negatively stained samples of SINV-3
      revealed isometric particles with apparent projections and a diameter of 27.3+/
      1.3 nm. SINV-3 was successfully transmitted to uninfected workers by feeding. The
      minus (replicative) strand of SINV-3 was detected in worker ants indicating
      replication of the virus. The possibility of using SINV-3 as a microbial control
      agent for fire ants is discussed.

PMID- 19403149
TI  - [Bing-Neel syndrome revealing Waldenstrom's macroglobulinemia].
AB  - INTRODUCTION: The most frequent neurological complication of Waldenstrom's
      macroglobulinemia is IgM-mediated polyneuropathy. Direct tumor cell infiltration
      of the nervous system is very rare and better known as the "Bing and Neel
      syndrome". This syndrome relates usually to a meningeal or meningo-myelo-cerebral
      tumor infiltration. OBSERVATION: A 54-year-old man developed a terminal cauda
      equina syndrome over several years. MRI disclosed lumbar roots infiltration and
      lumbar puncture the presence of lymphocytic meningitis with intrathecal synthesis
      of monoclonal IgM identical to that found in the blood. The bone biopsy revealed
      a lymphoplasmocytic infiltration consistent with the diagnosis of Waldenstrom's
      macroglobulinemia. The final diagnosis was meningeal and lumbar roots
      infiltration revealing Waldenstrom's macroglobulinemia. Partial remission was
      obtained after polychemotherapy with CHOP, rituximab and methotrexate. At the end
      of the treatment, the patient improved his bladder's control and was able to walk
      with a stick. DISCUSSION: We reviewed the 35 cases of "Bing and Neel syndrome" we
      have identified by a PubMed research. The present case report is original by the
      initial neurological presentation of the disease three years before diagnosis and
      the successful use of rituximab in the polychemotherapy regimen.

PMID- 19403156
TI  - Effects of aging and freeze-thawing on extractability of pyrene in soil.
AB  - The effects of soil freezing and thawing on the extractability by dichloromethane
      of pyrene from two Chinese soils are investigated. The soils were collected from
      the Northeast region of China where heavy pollution of soils by Polycyclic
      Aromatic Hydrocarbons (PAH) is common. Two soils were considered: a burozem
      obtained from the Shenfu irrigated region in Liaoning province and a phaeozem
      collected from the Hailun area in Haerbin province. The soils were collected from
      areas free from PAH pollution. Pyrene was aged in sterilized soil, and autoclaved
      deionized water was then added to adjust the soil to different moisture levels.
      The combined dichloromethane extractions of pyrene in soils at various periods
      showed that the quantity of pyrene extracted with dichloromethane could be
      divided into two stages: the initially rapid period and a longer, slower period.
      The frequency of freeze-thawing cycles had different and contradictory effects on
      pyrene extractability between the two soil types. Soil moisture also was found to
      have different and opposite effects on pyrene extractability. Freeze-thawing
      cycles had great influence on pyrene extractability both in aged and unaged
      soils. The changes in unaged soil were more significant than those in 1-year aged
      soil and attributed to changes in the soil organic matter. Our research shows
      that the effect of freezing and thawing on pyrene extraction is complicated due
      to the differences in physical and chemical properties of soils as well as the
      aging process.

PMID- 19403155
TI  - High cadmium concentrations in areas with endemic fluorosis: a serious hidden
      toxin?
AB  - Environmental contamination with cadmium (Cd) and fluorine (F) and the associated
      health impacts on humans have raised significant concerns in the literature, but
      the additional health risks created by Cd have not been investigated in areas
      with endemic fluorine intoxication (fluorosis). Here, we report for the first
      time that naturally occurring Cd in areas where endemic fluorosis is related to
      coal combustion is a serious hidden toxin. The high Cd levels in rocks and soils
      of these areas may increase health risks to epidemiological level, irrespective
      of fluorine levels. We implemented a pilot study in a fluorosis-affected rural
      area within China's Three Gorges region, and revealed enrichment of Cd in local
      bedrock (4.48-187 mgkg(-1)), coal (11.5-53.4 mgkg(-1)), and arable soils (1.01
      59.7 mgkg(-1)). Cadmium was also observed to concentrate in local food crops
      (0.58-14.9 mgkg(-1)) and in the urine of local residents (1.7-13.4 microgL(-1)).
      A routine epidemiological investigation revealed that the two major Cd exposure
      pathways were through crop consumption and inhalation of emissions from coal
      combustion. Therefore, the naturally occurring Cd in areas with endemic fluorosis
      related to coal combustion represents a previously unrecognized toxin that must
      be addressed as part of efforts to control the endemic problem. The
      biogeochemical processes of Cd and the associated environmental effects will
      require additional in-depth study.

PMID- 19403157
TI  - Assessment of the pesticides atrazine, endosulfan sulphate and chlorpyrifos for
      juvenoid-related endocrine activity using Daphnia magna.
AB  - The water flea Daphnia magna belongs to the cyclical parthenogenic species, which
      can reproduce by either parthenogenesis or sexual reproduction. Recent studies
      have reported the involvement of the methylfarnesoate hormone, in male sex
      determination of D. magna. The aim of this study was to evaluate the juvenoid and
      anti-juvenoid activity of atrazine, endosulfan sulphate, and chlorpyrifos. To
      assess the juvenoid activity we exposed maternal daphnids to several
      concentrations of the respective pesticides, using the percentage of male
      production as endpoint. Fenoxycarb (1microgL(-1)) was used as a positive control.
      The anti-juvenoid activity was assessed using a similar bioassay after the
      addition of fenoxycarb (1microgL(-1)) to all test solutions. Fenoxycarb is an
      insect growth regulator that mimics the action of methylfarnesoate, and promoted
      the production of 95% of male offspring at the given concentration. Weak juvenoid
      agonist activity was detected for endosulfan sulphate, with a significant
      increase of the percentage of male daphnids detected through logistic regression.
      In addition, atrazine and endosulfan sulphate antagonized the juvenoid activity
      of fenoxycarb. These results also corroborate the hypothesis that weak juvenoid
      agonists can simultaneously act as juvenoid antagonists as it has been observed
      in other hormonal systems.

PMID- 19403158
TI  - Effects of uranium-contaminated sediments on the bioturbation activity of
      Chironomus riparius larvae (Insecta, Diptera) and Tubifex tubifex worms
      (Annelida, Tubificidae).
AB  - Freshwater sediments represent a compartment for accumulation of toxic
      substances, notably of metallic pollutants such as uranium. However, they also
      constitute a privileged habitat for many benthic macro-invertebrate species with
      important roles in the functioning of these ecosystems, particularly through
      their bioturbation activities. Uranium accumulation in sediments can thus have
      harmful effects on these organisms (e.g., developmental delay, malformations,
      mortality). The present study aimed to evaluate the consequences of these effects
      on the bioturbation activity of Chironomus riparius larvae and Tubifex tubifex
      worms. These two species, which are widespread in freshwater ecosystems, are
      characteristic of two different modes of bioturbation: bioirrigation and upward
      bioconveying, respectively. By quantifying the burial and redistribution of
      fluorescent particulate tracers (microspheres), sediment reworking induced by
      these macro-invertebrates was measured after 12d of exposure. Biodiffusion D(b)
      and bioadvection W rates, as well as several other parameters, were estimated to
      assess and compare the bioturbation activity of the two species, separately and
      in combination, between uncontaminated and uranium-spiked sediments. The results
      reveal that C. riparius larvae were more sensitive to uranium, but their
      bioturbation activity, even under uncontaminated conditions, had little effect on
      sediment reworking. Particle mixing was mainly induced by T. tubifex worms, which
      were only affected by uranium at high concentrations in the sediment. Finally,
      bioturbation by T. tubifex led to a high degree of uranium release from sediment
      to the overlying water, which highlights the crucial role of this mostly dominant
      species on uranium biogeochemical cycles at concentrations existing in naturally
      contaminated sites.

PMID- 19403159
TI  - Sulfamethoxazole contamination of a deep phreatic aquifer.
AB  - Groundwater samples were obtained from the water table region of a phreatic
      aquifer (unsaturated zone depth up to 28 m) under land irrigated with wastewater
      effluents for about 5 decades and a relatively deep pumping well (109 m), used as
      a drinking water source till 2007, located downstream (1300 m) of wastewater
      effluent and sludge infiltration facilities. Sulfamethoxazole (SMX)
      concentrations in secondary effluents varied between 90 and 150 ng/L. SMX was
      extracted using SPE and was analyzed by HPLC-MS/MS. SMX (maximum concentration of
      37 ng/L) was detected in the water table region, in two monitoring wells, after
      an unsaturated zone transport period of about 16 years. The maximum SMX
      concentration detected in the pumping well was of 20 ng/L. These results question
      wastewater effluent disposal strategies including the suitability of irrigation
      with effluents on the replenishment area of an aquifer supplying drinking water.

PMID- 19403160
TI  - 210Pb and stable lead content in fungi: its transfer from soil.
AB  - The uptake and transfer of natural radionuclides, other than (40)K, from soil to
      mushrooms has been somewhat overlooked in the literature. Their contribution to
      the dose due to the consumption of mushrooms was considered negligible. But the
      contribution of (210)Pb in areas unaffected by any recent radioactive fallout has
      been found to be significant, up to 35% of the annual dose commitment in Spain.
      More than 30 species of mushrooms were analyzed, and the (210)Pb detected was in
      the range of 0.75-202 Bq/kg d.w. A slight difference was observed between species
      with different nutritional mechanisms (saprophytes > or = mycorrhizae). The
      (210)Pb content was correlated with the stable lead content, but not with its
      predecessor in the uranium radioactive series, (226)Ra. This suggested that
      (210)Pb was taken up from the soil by the same pathway as stable lead. The
      bioavailability of (210)Pb in soil was determined by means of a sequential
      extraction procedure (NH(4)OAc, 1M HCl, 6M HCl, and residue). About 30% of the
      (210)Pb present in the soil was available for transfer to mushrooms, more than
      other natural radionuclides in the same ecosystem. Lycoperdon perlatum, Hebeloma
      cylindrosporum, and Amanita curtipes presented the highest values of the
      available transfer factor, ATF. As reflected in their ATF values, the transfer
      from soil to mushroom of some natural and anthropogenic radionuclides was in the
      following order:

PMID- 19403162
TI  - Is randomized trial of neoadjuvant chemotherapy of ovarian cancer necessary?

PMID- 19403161
TI  - Bone formation in a rat calvarial defect model after transplanting autogenous
      bone marrow with beta-tricalcium phosphate.
AB  - In the present study, we evaluated the osteogenic potential of an autogenous bone
      marrow graft combined with beta-tricalcium phosphate (beta-TCP) in a rat
      calvarial bone defect model. The bone marrow harvested from the tibia of 7-week
      old rats was grafted autogenously in a calvarial defect together with beta-TCP
      (=BTG group, n=16) or without beta-TCP (=BG group, n=16). Groups of animals were
      also treated with beta-TCP alone (=TG group, n=16) and control animals (n=8)
      received no graft implanted into the defect. We then observed the process of bone
      formation by histology, enzyme histochemistry and immunohistochemistry. Five days
      after grafting, in the BTG and BG groups, cell proliferation and osteogenic
      differentiation were observed. From 5 to 10 days after surgery, active Runx2,
      osteopontin (OPN), and TRAP- positive cells appeared in the BTG and BG groups.
      New bone formation started in the defect in both the BTG and BG groups. At 30
      days after grafting, the BTG group showed new bone development and replacement of
      beta-TCP to fill the bone defect. New bone formation in the BTG group was
      significantly greater than in the BG group (P<0.01). The TG group showed no
      marked bone formation in the defect. The combination graft of bone marrow with
      beta-TCP showed marked bone formation in rat calvarial defects. Our results
      indicate that the combination grafts of bone marrow with beta-TCP may be an
      effective technique for repairing bone defects Beta-TCPgraft (TG) group.

PMID- 19403163
TI  - Options in the management of fertility-related issues after radical trachelectomy
      in patients with early cervical cancer.

PMID- 19403164
TI  - Cystic fibrosis.
AB  - Cystic fibrosis is the most common lethal genetic disease in white populations.
      The outlook for patients with the disease has improved steadily over many years,
      largely as a result of earlier diagnosis, more aggressive therapy, and provision
      of care in specialised centres. Researchers now have a more complete
      understanding of the molecular-biological defect that underlies cystic fibrosis,
      which is leading to new approaches to treatment. One of these treatments,
      hypertonic saline, is already in use, whereas others are in advanced stages of
      development. We review clinical care for cystic fibrosis and discuss recent
      advances in the understanding of its pathogenesis, implementation of screening of
      neonates, and development of therapies aimed at treating the basic defect.

PMID- 19403165
TI  - Bioaccumulation of the new antifoulant medetomidine in marine organisms.
AB  - Biofouling is a huge problem globally and new alternative antifoulants are
      presently being investigated. One candidate is medetomidine, a commonly used
      sedative in veterinary medicine, which has been shown to effectively prevent
      settlement of barnacles. The purpose of this study was to measure uptake,
      elimination and bioconcentration of medetomidine in Mytilus edulis, Abra nitida,
      Crangon crangon and periphyton communities to evaluate the risk of
      bioaccumulation in the marine environment. Bioconcentration factors (BCF) and
      bioaccumulation factors (BAF) were used to assess the bioaccumulation. The
      calculations of these factors were based on the distribution of the radiolabelled
      medetomidine. BCF for C. crangon was 2.8 while M. edulis had a BCF of 134 and the
      periphyton communities' BCF was 1195 l/kg fresh weight (FW). The concentration of
      medetomidine in the animals reached steady state after 24-48 h for all test
      systems except for A. nitida, which never stabilised enough to calculate a
      bioaccumulation factor (BAF). Elimination from the organism's tissues was rapid
      for three of the test systems with half-lives between 1 and 24 h. A. nitida had a
      half-life of 96-120 h. This study demonstrates that the bioconcentration and
      bioaccumulation of medetomidine differs between aquatic organisms and that
      microalgal communities in the form of periphyton have the highest
      bioconcentration factor of the organisms tested.

PMID- 19403166
TI  - The effect of Gd@C82(OH)22 nanoparticles on the release of Th1/Th2 cytokines and
      induction of TNF-alpha mediated cellular immunity.
AB  - It is known that down-regulation of the immune response may be associated with
      the progenesis, development and prognosis of cancer or infectious diseases. Up
      regulating the immune response in vivo is therefore a desirable strategy for
      clinical treatment. Here we report that poly-hydroxylated metallofullerenol
      (Gd@C(82)(OH)(22)) has biomedical functions useful in anticancer therapy arising
      from immunomodulatory effects observed both in vivo and in vitro. We found that
      metallofullerenol can inhibit the growth of tumors, and shows specific
      immunomodulatory effects on T cells and macrophages. These effects include
      polarizing the cytokine balance towards Th1 (T-helper cell type 1) cytokines,
      decreasing the production of Th2 cytokines (IL-4, IL-5 and IL-6), and increasing
      the production of Th1 cytokines (IL-2, IFN-gamma and TNF-alpha) in the serum
      samples. Immune-system regulation by this nanomaterial showed dose-dependent
      behavior: at a low concentration, Gd@C(82)(OH)(22) nanoparticles slightly
      affected the activity of immune cells in vitro, while at a high concentration,
      they markedly enhanced immune responses and stimulated immune cells to release
      more cytokines, helping eliminate abnormal cells. Gd@C(82)(OH)(22) nanoparticles
      stimulated T cells and macrophages to release significantly greater quantities of
      TNF-alpha, which plays a key role in cellular immune processes. Gd@C(82)(OH)(22)
      nanoparticles are more effective in inhibiting tumor growth in mice than some
      clinical anticancer drugs but have negligible side effects. The underlying
      mechanism for high anticancer activity may be attributed to the fact that this
      water-soluble nanomaterial effectively triggers the host immune system to
      scavenge tumor cells.

PMID- 19403167
TI  - A possible participation of gonadotropin-releasing hormone in the neuroleptic and
      cataleptic effect of haloperidol.
AB  - Haloperidol, an antipsychotic agent, stimulates the release of gonadotropin
      releasing hormone (GnRH), and this hormone is known to mimic some of the
      behavioral effects of haloperidol. Hence, the present study was carried out to
      find out the contribution of GnRH in the behavioral effects of haloperidol. The
      studies revealed that haloperidol (0.15, 0.25 and 0.5 mg/kg, i.p.) and leuprolide
      (GnRH agonist; 50, 100, 200 and 400 microg/kg, s.c.) dose-dependently inhibited
      conditioned avoidance response (CAR) in male Sprague-Dawley rats. In higher
      doses, haloperidol (0.5, 1 mg/kg, i.p.) and leuprolide (200, 400 microg/kg, s.c.)
      produced catalepsy in rats. Co-administration of sub-effective dose of leuprolide
      (50 or 100 microg/kg, s.c.) and haloperidol (0.15 or 0.5 mg/kg, i.p.) similarly
      inhibited CAR and induced catalepsy. Pre-treatment of rats with antide (GnRH
      antagonist; 10 microg/rat, s.c.), attenuated the inhibitory effect of both the
      agents on CAR; blocked leuprolide-induced catalepsy; and attenuated the intensity
      and reduced the duration of haloperidol-induced catalepsy. In conclusion, the
      studies suggest a possible role of GnRH in the neuroleptic and cataleptic effect
      of haloperidol.

PMID- 19403168
TI  - Bortezomib in combination with IGEV chemotherapy regimen for a primary refractory
      Hodgkin's lymphoma of bone.

PMID- 19403169
TI  - Identification of genes expressed as a result of lindane exposure in Oreochromis
      niloticus using differential display.
AB  - In order to assess the effect of lindane exposure on gene expression in tilapia
      (Oreochromis niloticus), twenty male fish were individually weighted and injected
      intraperitoneally with a single dose of lindane (19.09 mg/kg bw) using corn oil
      as a carrier vehicle, while a second group of twenty male fish (controls) was
      only injected with the carrier vehicle. Groups of four fish each were then
      sacrificed at 3, 6, 12, 18 and 24h after treatment application and total RNA was
      extracted from liver tissue. The differential display (DD) technique was then
      used to identify differentially expressed cDNA fragments between treatment and
      control fish. A total of fifty cDNA fragments were isolated and sequenced, from
      which only four showed homology with genes previously described in other fish
      species, namely the immunoglobulin heavy chain (IgH), coagulation factor V (FV),
      casein kinase 2 alpha (CK2a), and the receptor protein-tyrosine-like phosphatase
      (RPT-LP). The expression of such genes was confirmed using quantitative real time
      polymerase chain reaction (QRT-PCR). Results showed that lindane exposure
      triggered the differential expression of these genes during the first 6, 18 and
      24h subsequent to treatment application, suggesting that lindane exposure can
      trigger a rapid immune system response in tilapias.

PMID- 19403170
TI  - [Multiple calvarial cavernous hemangiomas].
AB  - Intraosseous cavernous hemangioma is rarely located in the calvarium. This benign
      tumor, arising from the intrinsic vasculature of bone, grows slowly over a period
      of years before it causes symptoms such as headaches or localized compression. We
      report here the case of a 27-year-old man, who presented with multiple calvarial
      cavernous hemangiomas associated with several hepatic hemangiomas. The patient
      had a family history of the disease, and is only the second case of multiple
      calvarial cavernous hemangiomas reported in the literature. The clinical,
      radiological and therapeutic aspects of this rare entity are also discussed.

PMID- 19403171
TI  - Infraorbital nerve schwannoma.

PMID- 19403172
TI  - [Susac syndrome, retinocochleocerebral microangiopathy: contribution of MRI].
AB  - This is a new case of Susac syndrome in a 27-year-old woman with polymorphic
      neurological disorders, her brain MRI showed multifocal hyperintense signals on
      T2-weighted images with possible effects on the corpus callosum. However,
      visualization of an occlusion in the retinal arterial branch of the right eye and
      hypoacusia on the right side allowed confirmation of the diagnosis. In this case
      report, we describe the imaging aspects of Susac syndrome and demonstrate that
      brain MRI allows the syndrome to be diagnosed at an early stage.

PMID- 19403174
TI  - Identification of interleukin-22 in gadoids and examination of its expression
      level in vaccinated fish.
AB  - This paper reports the cloning and sequencing of interleukin (IL)-22 in two
      gadoid fish, cod (Gadus morhua) and haddock (Melanogrammus aeglefinus). The
      complete transcript of this gene was 1002 and 1154 bp respectively, of which 492
      bp was the open reading frame (ORF) in both genes. High amino acid identity
      (88.3%) was found between these genes but was less than 50% aa identity to other
      known genes. The gene organisation of haddock IL-22 consisted of five exons and
      four introns, as with other IL-10 family members. Expression studies showed that
      IL-22 is constitutively expressed in gill, with low level expression also
      observed in gut, gonad and head kidney. In a vaccination experiment, haddock were
      injected intraperitoneally with formalin-killed Vibrio anguillarum or with PBS,
      and 2 months later challenged by immersion in 10(7)cfu/ml V. anguillarum for 30
      min. Head kidney and gill samples were collected prior to challenge and 24, 48
      and 72 h post-challenge (hpc) for Real-time PCR analysis of IL-22 expression. No
      significant changes in IL-22 expression were observed in head kidney tissue but
      vaccinated fish showed a significantly increased expression of IL-22 24 hpc in
      gill and no mortalities were seen in these fish. In contrast, control fish, which
      started to succumb to the disease from 72 hpc, showed no significant increase in
      gill expression after challenge.

PMID- 19403173
TI  - Beyond contaminated land assessment: on costs and benefits of bioaccessibility
      prediction.
AB  - Advances towards sustainable land management necessitate application of a broader
      portfolio of decision-support tools that improve evaluation of contaminated land.
      Over the last decade regulators have directed concerted effort towards
      rationalization of risk-based contaminated land policies recognizing
      bioavailability and bioaccessibility as concepts to be incorporated into risk
      assessments. The desire for a precise and rapid method to inform consideration of
      bioavailability and bioaccessibility to support risk assessment of contaminated
      land has never been greater. This study presents a comprehensive appraisal of
      both emerging non-exhaustive extraction techniques (subcritical water extraction
      and Brij 700 extraction) developed to reflect polycyclic aromatic hydrocarbon
      (PAH) bioaccessibility to microorganisms as well as formerly demonstrated
      methodologies (the use of cyclodextrins and butanol extraction). Application of
      unified evaluation criteria across different techniques enabled comparison not
      only from the bioaccessibility prediction perspective but also analysis of
      economical (cost of extraction) and practical (such as extraction time) measures.
      Whilst the use of cyclodextrins was the best predictor of the bioaccessible
      fraction for the majority of compounds, other methods appeared more cost- and
      time-effective. Juxtaposition of the techniques presented in this study assists
      establishing cost-benefit trade-offs of different non-exhaustive extraction
      techniques and contributes to tailoring information on contaminant
      bioaccessibility to support risk evaluation on contaminated sites.

PMID- 19403175
TI  - Antisense transcripts of V(D)J rearrangements; artifacts caused by false priming?
AB  - Somatic hypermutation (SH) of V(D)J rearrangements at the IGH and IGL loci
      diversifies the IG repertoire during the germinal center response. SH is
      absolutely dependent on the enzyme activation induced cytidine deaminase (AID)
      that initiates the SH process by deaminating C nucleotides in ssDNA. Mutations
      from G and C are thought to occur as a result of strand symmetrical deamination
      of C by AID on the coding and non-coding strands respectively. Mutations from A
      and T are introduced in a strand biased way during error prone repair of the AID
      induced lesion. SH is linked to transcription and it has been proposed that
      bidirectional transcription across V(D)J rearrangements occurs in activated and
      quiescent B cells and that it is co-opted to facilitate the accessibility of the
      two DNA strands by regulating accessibility of single stranded DNA to AID. We
      have developed a quantitative method to study directional transcription. Our
      method controls for differences in efficiency and specificity of reverse
      transcription that are known to be able to generate false positive data. This
      method does not detect antisense transcripts in exonic or intronic regions within
      the hypermutation domain of the spontaneously hypermutating cell line Ramos, or
      in human blood B cells or tonsil cells, providing convincing evidence that
      antisense transcripts are rare or absent in human B cells.

PMID- 19403176
TI  - Therapeutic effects of recombinant forms of full-length and truncated human
      surfactant protein D in a murine model of invasive pulmonary aspergillosis.
AB  - Aspergillus fumigatus (Afu) is an opportunistic fungal pathogen that can cause
      fatal invasive pulmonary aspergillosis (IPA) in immunocompromised individuals.
      Previously, surfactant protein D (SP-D), a surfactant-associated innate immune
      molecule, has been shown to enhance phagocytosis and killing of Afu conidia by
      phagocytic cells in vitro. An intranasal treatment of SP-D significantly
      increased survival in a murine model of IPA. Here we have examined mechanisms via
      which recombinant forms of full-length (hSP-D) or truncated human SP-D (rhSP-D)
      offer protection in a murine model of IPA that were immunosuppressed with
      hydrocortisone and challenged intranasally with Afu conidia prior to the
      treatment. SP-D or rhSP-D treatment increased the survival rate to 70% and 80%,
      respectively (100% mortality on day 7 in IPA mice), with concomitant reduction in
      the growth of fungal hyphae in the lungs, and increased levels of TNF-alpha and
      IFN-gamma in the lung suspension supernatants, as compared to untreated IPA mice.
      The level of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the lung
      cell suspension was also raised considerably following treatment with SP-D or
      rhSP-D. Our results appear to reaffirm the notion that under immunocompromised
      conditions, human SP-D or its truncated form can offer therapeutic protection
      against fatal challenge with Afu conidia challenge. Taken together, the SP-D
      mediated protective mechanisms include enhanced phagocytosis by recruited
      macrophages and neutrophils and fungistatic properties, suppression of the levels
      of pathogenic Th2 cytokines (IL-4 and IL-5), enhanced local production of
      protective Th1 cytokines, TNF-alpha and IFN-gamma, and that of protective C-C
      chemokine, MIP-1 alpha.

PMID- 19403177
TI  - The effect of trimipramine on dream recall and dream emotions in depressive
      outpatients.
AB  - Trimipramine is a sedating tricyclic antidepressant which is not only effective
      in the treatment of depression but also in primary insomnia. In contrast to most
      other antidepressants, trimipramine does not affect rapid eye movement sleep. In
      a large sample of depressive outpatients (N = 3926), the effect of trimipramine
      on dream recall and dream emotions was studied. The effect of trimipramine on
      dream recall was small and might be explained by the reduction of negatively
      toned dreams. The 4-week treatment with trimipramine yielded a considerable shift
      in dream emotions towards the positive end of the scale, which is paralleled by
      the decrease of symptom severity. The present findings support the continuity
      hypothesis of dreaming by demonstrating a close link between waking-life
      symptomatolgy and negative dream emotions. Future studies should analyze dream
      content in order to support the hypothesis that improvement in day-time symptoms
      is reflected in patients' dreams.

PMID- 19403178
TI  - Equine PSGL-1 modifications required for P-selectin binding.
AB  - Equine PSGL-1 (ePSGL-1) is widely expressed on equine PBMC as a homodimer with
      sialylation (sLeX) modifications that contribute to P-selectin binding affinity.
      To investigate the role of other potential post-translational modifications
      required for high-affinity P-selectin binding, ePSGL-1 was transfected into CHO
      cells expressing equine FucT-VII and/or C2GnT. P-selectin-IgG chimera binding by
      ePSGL-1 transfected into CHO cells only occurred when both FucT-VII and C2GnT
      were expressed, establishing that fucosylation and core-2 branching are required
      as post-translational modifications for high-affinity P-selectin binding.
      However, enzymatic removal of N-glycans or site and/or point-mutation preventing
      N-glycan addition did not inhibit P-selectin binding, indicating that N
      glycosylation is not required. Taken together, we hypothesized that sialylation,
      fucosylation, or core-2 branching must occur on O-glycans. The presence of
      numerous serine/threonine residues in the ePSGL-1 extracellular domain suggests
      several potential O-glycans attachment sites. P-selectin binding was also
      susceptible to OSGP cleavage, providing evidence for the existence of clustered,
      sialyated O-glycans on ePSGL-1. Because OSGP eliminated ePSGL-1 precipitation the
      P-selectin binding domain of ePSGL-1 must contain clustered, sialyated,
      fucosylated, and core-2 branched O-glycans. Using point-mutation deletion
      techniques, the binding domain was determined to reside between residues 48 and
      100 of ePSGL-1. Sulfation, a critical modification for human PSGL-1 binding to P
      selectin, was not necessary for equine P-selectin binding, while dimerization of
      ePSGL-1 was critical. These species-specific features of equine PSGL-1 provide
      new information that advances our understanding of high-affinity P-selectin
      binding mediated mononuclear cell trafficking.

PMID- 19403179
TI  - Experience of the school-aged child with tracheostomy.
AB  - BACKGROUND: Little is known about the school experience of children with
      tracheostomy tubes. These children may represent a population that qualifies for
      special services in school. Understanding how tracheostomy affects school-aged
      children may provide information needed to develop programs that provide these
      children with invaluable experiences. OBJECTIVE: To understand what children with
      tracheostomies experience in school as it relates to tracheostomy care and how
      their condition affects academic achievement and social adjustment. METHODS: We
      identified a cohort of 38 eligible school-aged children with indwelling
      tracheostomy tubes for ongoing upper airway obstruction through the North
      Carolina Children's Airway Center. A questionnaire was developed to assess
      support of their medical condition throughout the school day. Twenty-three
      patients responded to the questionnaire. RESULTS: School experience for a child
      with a tracheostomy varied. Approximately half the children attended special
      needs classes, the other half were in mainstream classrooms. Speech services and
      Passy-Muir valves were used in 43% and 57% of cases, respectively. Over half the
      students were excluded from physical activity because of the tracheostomy. Most
      students missed at least 10 days of school for medical care in an academic year.
      Fifty percent of the students reported attending schools where school personnel
      had no training in tracheostomy care. In some cases, a trained nurse accompanied
      the child to school to help with tracheostomy care. In other cases, the child
      coped with tracheostomy care alone. CONCLUSIONS: As children with special medical
      needs are increasingly incorporated into mainstream schools, it is important to
      understand the potential hurdles they face in managing tracheostomies. In
      particular, school personnel should have the ability to provide basic care for
      students with tracheostomies. Student speech and educational outcomes require
      further investigation and analysis.

PMID- 19403180
TI  - Medial or medio-lateral graft tympanoplasty for repair of tympanic membrane
      perforation.
AB  - OBJECTIVE: To describe and evaluate the medio-lateral graft tympanoplasty(1) for
      the reconstruction of anterior or subtotal tympanic membrane (TM) perforation and
      medial graft tympanoplasty for posterior TM perforation. METHODS: Retrospective
      study of 200 patients who underwent medio-lateral graft tympanoplasty (100 cases)
      and medial graft tympanoplasty (100 cases) at community and tertiary care medical
      centers from 1995 to 2006. All patients underwent preoperative and postoperative
      audiograms. In the medial graft tympanoplasty, the graft is placed entirely
      medial to the remaining TM and malleus. First, margin of TM perforation is
      denuded removing ring of squamous tissue. Tympanomeatal flap is elevated.
      Temporalis fascia is harvested, semidried, and grafted medial to the TM
      perforation and malleus with Gelfoam packing supporting the graft. In the medio
      lateral graft technique, posterior tympanomeatal flap is elevated same as in the
      medial graft tympanoplasty first. Anterior-medial canal skin is elevated down to
      the annulus. At the annulus only squamous epithelial layer of TM is elevated up
      to anterior half of the TM perforation. Temporalis fascia is grafted medial to
      posterior half of the perforation and lateral to anterior half of the de
      epithelialized TM perforation up to the annulus. Anterior canal skin is rotated
      to cover the fascia graft and TM perforation as a second layer closure. Patients
      were followed for at least six months. Outcome was considered successful if TM is
      healed and intact. RESULTS: There were four failures (96% success rate) in medial
      graft method for posterior TM perforation due to infection and re-perforation. In
      the medio-lateral graft tympanoplasty, there were three failures (97% success
      rate) due to a postoperative infection, anterior blunting and recurrent
      cholesteatoma. CONCLUSION: The medial graft tympanoplasty works well for
      posterior TM perforation. The medio-lateral graft method is an excellent method
      for the reconstruction of large anterior or subtotal TM perforation. This new
      method should help otologic surgeons to improve outcome of tympanoplasty for
      anterior or subtotal TM perforation.

PMID- 19403181
TI  - Hepatic and vascular mRNA expression in adult zebrafish (Danio rerio) following
      exposure to benzo-a-pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - Developmental exposure to aryl hydrocarbon receptor (AhR) agonists in fish causes
      severe defects in the cardiovascular system. However, the effects of acute AhR
      agonist exposure on the adult fish cardiovascular system are not clear. We
      hypothesized that AhR-mediated changes in adult vascular tissue gene expression
      would differ from that of hepatic tissue. Therefore, zebrafish (Danio rerio) were
      intraperitoneally injected with the AhR agonists benzo-a-pyrene (BaP; 1mg/kg) or
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 20microg/kg) alone and in combination
      with the AhR antagonists resveratrol (Res; 10mg/kg) or alpha-naphthoflavone (ANF;
      50mg/kg). Hepatic and mesenteric artery cytochrome P450 enzyme (subtypes 1A, 1B1,
      1C1, and 1C2) and cyclooxygenase enzyme (subtypes 1, 2a, and 2b) mRNA expression
      was quantified using real-time reverse transcriptase PCR. TCDD exposure
      significantly increased (p<or=0.05 in Tukey's posteriori test after 1-way ANOVA;
      n=4-6/group) CYP1A, CYP1C1, and COX-2b mRNA expression in hepatic tissue (105+/
      21, 12+/-2, and 2+/-0.3 fold-increase, mean+/-SEM respectively). TCDD also
      increased CYP1A, CYP1B1, CYP1C1, CYP1C2, and COX-1 mRNA expression in mesenteric
      artery (121+/-23, 5+/-1, 28+/-6, 7+/-1, and 3+/-0.3, respectively). Importantly,
      while BaP exposure elicited no significant alterations in hepatic CYP mRNA
      expression, it increased COX-1 and COX-2b in liver tissues (3+/-1 and 2+/-0.1,
      respectively), as well as CYP1A, CYP1B1, CYP1C1, CYP1C2, and COX-1 expression in
      mesenteric artery (2+/-0.3, 4+/-0.3, 5+/-1, 5+/-1, and 2+/-0.3, respectively).
      Resveratrol was able to antagonize TCDD-induced CYP1C2 in mesenteric artery but
      was without effect in all other treatments in both liver and mesenteric artery.
      In contrast, ANF antagonized TCDD and BaP-induced COX-2b and TCDD-induced CYP1C1
      expression increases, as well as reduced baseline CYP1B1 and COX-2a expression in
      liver, while failing to affect BaP and TCDD-induced hepatic CYP1A increases.
      However, in mesenteric artery, ANF alone acted instead as an agonist to increase
      expression of CYP1A, CYP1B1, CYP1C1, CYP1C2, COX-2a and COX-2b. Thus, there are
      important differences in response to both AhR agonists and antagonists between
      liver and mesenteric artery in adult zebrafish. The vascular-specific changes in
      gene expression will be linked to future studies examining alterations in
      cardiovascular function produced by acute AhR agonist exposure in adult fish.

PMID- 19403182
TI  - Low plasma adiponectin levels are associated with presence of thin-cap
      fibroatheroma in men with stable coronary artery disease.
AB  - BACKGROUND: Previous studies demonstrated the inverse association of adiponectin
      with coronary artery disease (CAD) especially in men with acute coronary
      syndrome, however their association with in vivo plaque vulnerability in stable
      CAD, which may be reflected by the thin-cap fibroatheroma (TCFA) prevalence,
      remains unknown. METHODS: In 50 men with stable CAD, we identified TCFA with
      multi-vessel examination of combined use of virtual histology intravascular
      ultrasound (VH-IVUS) and optical coherence tomography (OCT). The definition of
      TCFA was described as follows; necrotic-core rich lesion (% necrotic-core >10%)
      without evidence of an overlying fibrous component and % plaque-volume >40% in at
      least 3 consecutive frames by VH-IVUS, and the thinnest fibrous-cap thickness <65
      microm by OCT. The patients were divided into two groups, patients with TCFA and
      without TCFA, and plasma adiponectin level was compared between the groups.
      RESULTS: Among 50 patients, we could observe 116 vessels (2.32+/-0.47
      vessel/patient). At least one TCFA was identified in 20 patients. Patients with
      TCFA had significantly lower plasma adiponectin levels than patients without TCFA
      (P<0.0001). Furthermore, the plasma adiponectin levels in patients with multi
      vessel TCFA were significantly lower than those in patients with single-vessel
      TCFA (P=0.049). Multivariate logistic regression analysis revealed that plasma
      adiponectin was the strongest predictive factor of the presence of TCFA
      (P=0.0007). CONCLUSIONS: Low plasma adiponectin was associated with the presence
      of TCFA in men with stable CAD. This finding suggests that, in these subjects, it
      may be a biomarker that can be used to stratify "vulnerable patients" into risk
      categories.

PMID- 19403183
TI  - Adjunctive application of handgrip exercise associated with dobutamine stress
      echocardiography.

PMID- 19403185
TI  - Get it off your chest--or outplacement and the big picture under scrutiny.
AB  - In the olden days of medicine case histories were considered essential in the
      conveyance of knowledge. Today they rather form a museum of curiosities, a
      pattern-card of phenomena not seldom combining an eventful clinical course and
      technical interference in its broadest sense. A case of eventration is put on the
      stage as an example of imaging ability. Irreversible technological advance makes
      it important to find the necessary balance between human needs and diagnostic
      potential. Imaging, how sophisticated it may be, should always be part of the big
      picture when it comes to decision making and follow up. Reappraisal of the chest
      X-ray, one of the icons of medicine is warranted.

PMID- 19403186
TI  - Hashitoxicosis with pericardial effusion.
AB  - Previous studies have suggested that subclinical thyroid dysfunction is
      associated with detrimental effects on the cardiovascular system. Subclinical
      hyperthyroidism is an increasingly recognized entity that is defined as a normal
      serum free thyroxine and free triiodothyronine levels with a TSH level suppressed
      below the normal range and usually undetectable. It has been reported that
      subclinical hyperthyroidism is not associated with coronary heart disease or
      mortality from cardiovascular causes but it is sufficient to induce arrhythmias
      including atrial fibrillation and atrial flutter. It has also been reported that
      increased factor X activity in patients with subclinical hyperthyroidism
      represents a potential hypercoagulable state. Subclinical hypothyroidism is
      defined by elevated serum levels of TSH with normal levels of free thyroid
      hormones. Subclinical hypothyroidism is characterized by abnormal lipid
      metabolism, cardiac dysfunction, diastolic hypertension conferring an elevated
      risk of atherosclerosis, and ischemic heart disease. It has been reported that
      sub-clinical hypothyroidism is associated with both, a significant risk of
      coronary heart disease at baseline and at follow-up and that mortality from
      cardiovascular causes is significantly higher at follow-up. However subclinical
      thyroid dysfunction is currently the subject of numerous studies and remains
      controversial, particularly as it relates to cardiovascular morbidity and
      mortality and clinical applications. Pericardial effusion can be present in
      systemic disorders including hypothyroidism and subclinical hypothyroidism too.
      Pericardial effusion is extremely rare as an expression of hyperthyroidism. We
      present a case of pericardial effusion associated with a subclinical
      hyperthyroidism during the hyperthyroid phase of the chronic autoimmune
      thyreopathy (Hashitoxicosis).

PMID- 19403184
TI  - Influence of weather on daily hospital admissions for acute myocardial infarction
      (from the Korea Acute Myocardial Infarction Registry).
AB  - BACKGROUND: We investigated the association between meteorological parameters and
      hospital admissions for acute myocardial infarction (AMI) in a temperate and
      continental climate, Korea. METHODS: From the Korean AMI Registry, 2136 Koreans
      admitted for AMI in four university hospitals in Daegu city from November 2005 to
      October 2007 were included in this study. We calculated the incidences of AMI per
      season, per month, and per day-of-week. The meteorological parameters, including
      air temperature, relative humidity, wind speed, sunshine duration, and a thermo
      hydrological index, were provided by the database of the Korea Meteorological
      Administration. Generalized additive Poisson models were used. RESULTS: Seasonal
      variations were noted for AMI, characterized by winter peak and summer trough
      (p<0.001). Monthly occurrence rate of AMI was highest in January and lowest in
      October (p<0.001). There were significant associations between hospital
      admissions and meteorological parameters including air temperature, relative
      humidity, and sunshine duration after controlling for effects of day-of-week,
      season, and holidays (p<0.05). These associations were stronger in females and
      the younger age (<65 years) (p<0.01). CONCLUSIONS: The incidence of AMI shows
      seasonal and monthly variations. Meteorological parameters have a significant
      influence on the occurrence of AMI, particularly in females and the younger age.

PMID- 19403187
TI  - Long-term clinical outcome with titanium-nitride-oxide-coated stents and
      paclitaxel-eluting stents for coronary revascularization in an unselected
      population.
AB  - BACKGROUND: The aim of this study was to evaluate long-term clinical events in
      patients treated with titanium-nitride-oxide-coated bio-active stents (BAS) and
      paclitaxel-eluting stents (PES) in routine clinical practice. METHODS: All
      patients undergoing percutaneous coronary intervention (PCI) were eligible for
      this single-centre registry between May 2003 and November 2004. The primary end
      point of the study was major adverse cardiac events (MACE) at 3 years including
      myocardial infarction (MI), cardiac death and target vessel revascularization
      (TVR). RESULTS: A total of 201 patients received BAS and 204 patients PES. In
      addition, during the same study period, 184 patients were treated with bare-metal
      stents (BMS) and 125 patients underwent CABG. Complete follow-up datasets were
      available in all patients. After 3 years of follow-up, the rate of MACE was 13.9%
      for BAS and 23.5% for PES (adjusted HR 2.0, 95% CI 1.2-3.2, p=0.006). This
      difference was mainly driven by a higher incidence of MI in the PES group (19.1%)
      compared with the BAS (7.5%) group (adjusted HR 3.2, 95% CI 1.7-5.8, p<0.001).
      The rate of MACE was 31.5% in the BMS group and 4% in the CABG group. At 3 years,
      stent thrombosis occurred in 15 patients in the PES (7.4%) group. There was no
      stent thrombosis in the BAS group. CONCLUSIONS: After the 3 year follow-up, BAS
      resulted in better long-term outcome compared with PES with infrequent need for
      TVR.

PMID- 19403188
TI  - Interatrial defect and patent ductus arteriosus.
AB  - We greatly appreciated the letter to the Editor by Rana Olgunturk and Serdar
      Kula. We can say that his interpretation coincides with our interpretation and
      with the knowledge about patent ductus arteriosus (PDA) and secundum atrial
      septal defects. Although functional closure of PDA usually occurs in the first
      few hours of life in healthy infants born at term (about 15 h of life in healthy
      infants born at term), true anatomic closure, in which the ductus loses the
      ability to reopen, may take several weeks. Persistent, patency for up to 10 days
      after birth is encountered in premature infants. The male Italian newborn infant
      of the cited case report was referred at the age of 2 days to the Cardiology Unit
      for a cardiovascular check-up (in the text: "in a 3-day-old newborn infant" must
      be comprehended as "in a 2-day-old newborn infant") and was mature. Interatrial
      septal shunts in newborns are frequently encountered. Since there are no
      definitive diagnostic criteria for both patent foramen ovale and secundum atrial
      septal defects, it is difficult to differentiate these two lesions by
      echocardiography, particularly in the early newborn period. Some authors, called
      these two lesions as "interatrial septal openings". The diagnosis, in the case
      report cited, was made not only on the basis of the first observation but also on
      the basis of the persistence of abnormalities during the long-term follow-up and
      therefore the infant was referred to a pediatric heart surgical unit were the
      abnormalities were confirmed.

PMID- 19403189
TI  - Theories and models for 1/f(beta) noise in human movement science.
AB  - Human motor behavior is often characterized by long-range, slowly decaying serial
      correlations or 1/f(beta) noise. Despite its prevalence, the role of the
      1/f(beta) phenomenon in human movement research has been rather modest and
      unclear. The goal of this paper is to outline a research agenda in which the
      study of 1/f(beta) noise can contribute to scientific progress. In the first
      section of this article we discuss two popular perspectives on 1/f(beta) noise:
      the nomothetic perspective that seeks general explanations, and the mechanistic
      perspective that seeks domain-specific models. We believe that if 1/f(beta) noise
      is to have an impact on the field of movement science, researchers should develop
      and test domain-specific mechanistic models of human motor behavior. In the
      second section we illustrate our claim by showing how a mechanistic model of
      1/f(beta) noise can be successfully integrated with currently established models
      for rhythmic self-paced, synchronized, and bimanual tapping. This model synthesis
      results in a unified account of the observed long-range serial correlations
      across a range of different tasks.

PMID- 19403190
TI  - Influence of acid stress on survival, expression of virulence genes and invasion
      capacity into Caco-2 cells of Listeria monocytogenes strains of different
      origins.
AB  - The influence of food-related acid stress on the virulence capacity of Listeria
      monocytogenes was evaluated. The survival of acid-adapted and non-adapted L.
      monocytogenes cells during exposure to lethal concentrations of acetic acid was
      monitored. Also the effect of sublethal acid stress exposure on the expression
      levels of several virulence genes and on the capacity to invade Caco-2 cells was
      analyzed. Acid-adapted and non-adapted cells showed different acid tolerance
      response (ATR) patterns. Our data also demonstrate that pre-exposure to sublethal
      acid stress might lead to gadD2 induction. However, no correlation with the
      origin of the strain and with the ATR was noticed, indicating that probably other
      genes also could play an important role in this ATR mechanism. Additionally, our
      data showed that acid adaptation could influence the virulence capacity by
      regulating the expression levels of virulence genes. Moreover, the inlA
      expression data strongly correlated with the results of the in vitro invasion
      study. These results lead to the indication that low pH and acetic acid, used in
      minimally processed food products, might influence the virulence potential of L.
      monocytogenes.

PMID- 19403191
TI  - Relationship between serum retinol-binding protein 4 and visfatin and the
      metabolic syndrome.
AB  - BACKGROUND: This study investigates the relationship between serum concentration
      of RBP4 and visfatin and the metabolic syndrome. METHODS: Patients with metabolic
      syndrome were studied between October, 2004 and September, 2005. All study
      subjects were aged 40 and over and lived in Taichung city, Taiwan. The Third
      Report of the National Cholesterol Education Program's Adult Treatment Panel (ATP
      III, 2001) was used to define the metabolic syndrome. Serum RBP4 and visfatin
      levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum mean
      RBP4 levels in subjects who had all five abnormal components of metabolic
      syndrome (mean+/-SD=40.8+/-18.6) and those who had all components except
      hyperglycemia (43.5+/-23.5) were significantly higher than those in healthy
      controls (30.3+/-14.0 microg/ml) (p<0.05). Similar results were not found in
      serum visfatin levels. Using log-transformed serum RBP4 or visfatin levels as a
      dependent variable, we found that subjects with all five and four abnormal
      components of metabolic syndrome had significantly higher mean serum RBP4 levels
      (p=0.043 and 0.034, respectively), compared to healthy controls, after adjusting
      for other covariates. In contrast, similar results were not found in serum
      visfatin levels. CONCLUSION: Metabolic syndrome is significantly associated with
      serum RBP4, but not serum visfatin.

PMID- 19403192
TI  - Language barriers in health and social care consultations in the community: a
      comparative study of responses in Ireland and England.
AB  - OBJECTIVE: This paper focuses on the implications of migration for host health
      and social care systems in terms of linguistic diversity, language barriers and
      language supports. The objective is to compare Ireland, as a context responding
      to the new challenge of language barriers in healthcare, and England, as a
      context in which the management of language barriers is being re-assessed.
      METHODS: Empirical data from two action research studies in Ireland and England
      are compared. The combined data set is 146 data collection episodes with service
      users with limited English and their health and social care providers. RESULTS:
      Key findings are that the same range of formal and informal responses to language
      barriers occurs in practice in both contexts but proportions of knowledge and use
      of these responses differ. English service providers have more awareness about
      the use of formal responses than Irish service providers but uptake of formal
      responses remains low in both contexts. Data from service users confirms these
      findings. CONCLUSIONS: There is a need for more attention to the implementation
      of policies for language barriers in both Ireland and England, further research
      about the normalization processes associated with these consultations and
      knowledge transfer networks to facilitate on-going dialogue between all key
      stakeholders with an emphasis on supporting service users' involvement and
      participation.

PMID- 19403193
TI  - Simulation program for power and sample size determination in logistic analysis
      of single nucleotide polymorphisms when the response variable is subject to
      misclassification.
AB  - The main objective of this study was to develop a simulation program to determine
      the sample size for a clinical study to confirm a genetic-disease association
      observed in a retrospective exploratory study. The effect of misclassification of
      a binary response variable on the power is also investigated. A general
      expression for the magnitude of the decrease in statistical power due to
      misclassification is obtained based on the Pitman asymptotic relative efficiency.
      The simulation program presents an estimate of the exact power when
      misclassification exists. Running the program several times under different
      settings of parameters, it revealed that the effect of even low misclassification
      rates is serious. Response misclassification should be taken into consideration
      when determining the sample size. The program can be used on the Internet.

PMID- 19403194
TI  - Bateman's principles and human sex roles.
AB  - In 1948, Angus J. Bateman reported a stronger relationship between mating and
      reproductive success in male fruit flies compared with females, and concluded
      that selection should universally favour 'an undiscriminating eagerness in the
      males and a discriminating passivity in the females' to obtain mates. The
      conventional view of promiscuous, undiscriminating males and coy, choosy females
      has also been applied to our own species. Here, we challenge the view that
      evolutionary theory prescribes stereotyped sex roles in human beings, firstly by
      reviewing Bateman's principles and recent sexual selection theory and, secondly,
      by examining data on mating behaviour and reproductive success in current and
      historic human populations. We argue that human mating strategies are unlikely to
      conform to a single universal pattern.

PMID- 19403195
TI  - Improved accumulation of ajmalicine and tetrahydroalstonine in Catharanthus cells
      expressing an ABC transporter.
AB  - The biosynthetic pathway of monoterpenoid indole alkaloids in Catharanthus roseus
      is located throughout various membranes at both the cellular and intercellular
      levels. ATP-binding cassette (ABC) transporters are known to export vincristine
      and vinblastine from human cancer cells. It has recently been shown that ABC
      transporters are also involved in the transport of various monoterpenoid
      alkaloids in Catharanthus roseus cells. Over-expression of an ABC transporter in
      this plant might therefore affect the regulation of the alkaloid biosynthetic
      pathway. CjMDR1, an ABC transporter gene originally isolated from Coptis
      japonica, was expressed in Catharanthus roseus cell cultures. Cells showing a
      positive PCR signal of the transgene in both cDNA and genomic DNA samples were
      subject to transport studies using selected substrates. Unexpectedly, transport
      of the isoquinoline alkaloid berberine, the main substrate of CjMDR1 transporter
      in Coptis japonica, was not affected as compared with control and wild-type
      Catharanthus cells. On the other hand, the endogenous alkaloids ajmalicine and
      tetrahydroalstonine were accumulated significantly more in Catharanthus roseus
      cells expressing CjMDR1 in comparison with control lines after feeding these
      alkaloids.

PMID- 19403196
TI  - Autoregulation of nodulation (AON) in Pisum sativum (pea) involves signalling
      events associated with both nodule primordia development and nitrogen fixation.
AB  - To define the signalling events required for the activation of AON, we utilised
      approach grafts between wild-type pea plants and their mutants defective at
      successive stages of nodule formation. AON signalling strength was monitored by
      prior inoculation of mutant root portions (as so-called 'sensor') and quantifying
      nodule formation on connected roots of delayed inoculated wild type (the
      'reporter'). Detectable AON sensing and associated signal exchange between root
      and shoot started after root hair curling but before the initiation of visible
      cortical and pericycle cell divisions. The strength of AON signalling was
      correlated with the stage of nodule development and size of nodule, with mature
      nitrogen-fixing nodules possessing the strongest AON-inducing signal. We
      demonstrated that the pea supernodulating mutant nod3 may function pre-NARK in
      the root. A model for the activation of AON signalling and its potential
      relationship with cell division, nitrogen fixation and/or cytokinin signal
      transduction are presented.

PMID- 19403197
TI  - Protecting health care workers from tuberculosis: a 10-year experience.
AB  - BACKGROUND: Cook County Hospital (CCH) is an inner-city, large public hospital.
      Twenty-five percent of Chicago's tuberculosis (TB) cases are diagnosed at CCH. We
      wanted to review and analyze interventions implemented over a 10-year period at
      CCH to prevent TB infection in health care workers. METHODS: We performed a
      retrospective review of interventions to prevent health care-associated
      tuberculosis. We collated and analyzed tuberculin skin test conversions in our
      employees for the same time period. RESULTS: From 1990 to 2002, we cared for over
      1800 in-patients with tuberculosis. During 1992-1997, multiple interventions to
      eliminate health care-associated spread of tuberculosis were implemented.
      Tuberculin skin test conversions in our employees decreased markedly from January
      1994 through December 2002. Two drops in tuberculin skin test conversion rates
      occurred: one after introduction of basic administrative and engineering controls
      and a second after we experienced a decrease in missed TB cases and the
      introduction of N-95 personal respirators with 1-time qualitative fit testing.
      CONCLUSION: Our annual health care worker skin test conversion rate fell
      significantly when our primary interventions were relatively simple
      administrative and engineering controls. Educating health care workers to
      promptly recognize patients with TB and placing exhaust fans to create negative
      pressure respiratory isolation rooms were probably our 2 most potent infection
      control measures.

PMID- 19403198
TI  - [Gait impairment and dysphagia due to a giant basilar aneurysm in a
      nonagenarian].
AB  - We describe the case of a 90-year-old woman with a giant fusiform cerebral
      aneurysm of the basilar artery who developed progressive ataxia and dysphagia.
      The interest of this case lies in the type, size, localization and clinical
      manifestations of the aneurysm. We analyze the case and review the main features
      of this entity.

PMID- 19403199
TI  - [Hypertension in the very old: to treat or not to treat?, that is not yet the
      question].

PMID- 19403200
TI  - [Laboratory manifestations associated with chronic renal failure: what degree of
      estimated glomerular filtration can be used for its detection in the elderly?].
AB  - OBJECTIVE: A classification of chronic kidney disease (CKD) based on stages of
      glomerular filtration (GF) has recently been developed. Thus, chronic renal
      failure (CRF) is based on GF <60 ml/min. Our goal was to study the presence of
      typical manifestations of CRF in elderly individuals with a GF of <60 ml/min
      (stage 3-5) and to determine the cut-off value at which GF can be used to detect
      these manifestations. MATERIAL AND METHODS: We performed a cross-sectional study
      in clinically-stable elderly patients attending the geriatrics and nephrology
      outpatient department. The estimated GF (GFe) was established with the Cockroft
      Gault and abbreviated Modification of Diet in Renal Disease Study (MDRD)
      formulae. Because these patients had a GF of less than 60 ml/min, they were
      expected to show the manifestations associated with CRF (anaemia, metabolic
      acidosis, abnormal bone and mineral metabolism). We evaluated the occurrence of
      these manifestations and the GF cut-off at which they were detected. To do this,
      the population was divided into two groups: group A: patients with GFe > or = 30
      ml/min (stage 3, N=48); and group B: patients with GFe <30 ml/min (stages 4-5,
      N=8). RESULTS: Seventy percent of the patients had a GFe (MDRD) <60 ml/min (stage
      3-5). Despite reduced GF, these patients did not show the typical manifestations
      of CRF. Group B showed higher plasmatic levels of creatinine, urea, uric acid,
      and potassium and required treatment with erythropoietin and calcium salts.
      CONCLUSIONS: Many elderly people diagnosed with CKD with the current
      classification do not show manifestations of CRF. Estimation of the GF in elders
      should be generalized to correctly adjust medication to renal impairment rather
      than to classify elders into CKD stage.

PMID- 19403201
TI  - [A model for making shared decisions with the patient].

PMID- 19403202
TI  - [Concept and tools].

PMID- 19403203
TI  - [Pasteurella multocida meningitis: report of 2 cases].

PMID- 19403204
TI  - [Frequency and antifungal profile of Candida isolated from vaginal exudates of
      preadolescent girls].

PMID- 19403205
TI  - [Prevalence of antibodies against hepatitis A and B in HIV-1-infected children
      and adolescents].
AB  - INTRODUCTION: Patients coinfected with HIV and hepatitis B virus (HBV) have a
      higher risk of developing chronic HBV infection and a higher risk of
      hepatotoxicity. Hepatitis A virus (HAV) in HIV-infected patients may require
      antiretroviral treatment interruption, producing prolonged viremia. In this
      study, we assess the prevalence of protective antibodies in these patients.
      METHODS: A cross-sectional study was conducted to determine the prevalence of IgG
      antibodies against HAV and antibody against HBs (anti-HBs) in a cohort of 121 HIV
      infected children and adolescents (1-19 years), followed-up in 4 public hospitals
      in Madrid (Spain). RESULTS: Among the total, 12.4% (95% CI: 7.1-19.6%) of
      children and adolescents had positive serology for HAV. Children of immigrant
      origin presented a higher percentage than children born in Spain: 50% vs. 6.2%,
      respectively (P<0.001). In addition, 16.5% (95% CI: 10.4-24.3) of the study
      population had protective anti-HBs. A higher percentage of children with anti-HBs
      antibodies was seen in CDC clinical category A: 20% vs. 16% of those in clinical
      category B vs. 9.4% of those in clinical category C (P=0.19). The percentage of
      positive-positive children progressively decreased according to the years elapsed
      since HBV vaccination. DISCUSSION: Most HIV-infected children and adolescents
      have no protective antibodies against natural infection by HBV and HAV. More
      studies are needed to define the best vaccination strategy to achieve a higher
      percentage of patients protected against these infections.

PMID- 19403206
TI  - Characterization of the enzyme aac(3)-Id in a clinical isolate of Salmonella
      enterica serovar Haifa causing traveler's diarrhea.
AB  - INTRODUCTION: The objective of this investigation was to identify the mechanism
      of decreased susceptibility to gentamicin in a Salmonella clinical isolate,
      leading to the detection of a aminoglycoside acetyltransferase gene found in a
      class 1 integron. METHODS: A multidrug-resistant Salmonella strain was recovered
      from feces of a traveler to Egypt. The antimicrobial susceptibility test to 12
      antimicrobial agents was performed with the Kirby-Bauer method. The presence of
      class 1 integron was determined by PCR. The amplified product was recovered and
      sequenced in order to establish the genes carried. In addition, susceptibility to
      gentamicin C1a, gentamicin C1, sisomicin, neomycin, dibekacin, kanamycin,
      tobramycin, amikacin, netilmicin, apramycin, dactimicin, spectinomycin,
      streptomycin, lividomycin and butirosin, was established. The Champion pET101
      Directional TOPO Expression Kit was used to clone and express the aac(3)-I gene.
      RESULTS: The isolate was identified as Salmonella enterica serovar Haifa, showing
      resistance to nalidixic acid, tetracycline and decreased susceptibility to
      gentamicin. One integron with a size circa 1,500 bp, encoding an aac(3)-Id plus
      aadA7 genes was observed. The analysis of the susceptibility to different
      aminoglycosides in the E. coli TOP10F' transformed with the vector carrying
      aac(3)-Id gene showed resistance to gentamicin C1a, gentamicin C1, and
      dactimicin, in accordance with the presence of this enzyme but, was susceptible
      to sisomicin. The homology of the amino acid and nucleotide sequences with the
      AAC(3)-Id enzyme was of 100%. CONCLUSION: The presence of the AAC(3)-Id enzyme
      was described for the first time in a S. Haifa.

PMID- 19403208
TI  - [Acute meningitis and spondylodiscitis due to Streptococcus suis in a patient who
      had no contact with pigs or porcine products].

PMID- 19403207
TI  - [Human reservoirs of Pneumocystis].
AB  - Pneumocystis jirovecii, the fungal agent that causes Pneumocystis pneumonia
      (PCP), is known to exclusively infect humans. Molecular studies have enabled
      detection of this fungus in individuals who have been colonized by P. jirovecii.
      Such colonization, found in several populations, seems to act as a human
      reservoir for the fungus. Various studies have reported mutations associated with
      sulfa resistance in P. jirovecii strains isolated from colonized patients, who
      can transmit the mutant genotype to PCP-susceptible individuals. The growing
      interest in P. jirovecii colonization may prompt the design of new prevention and
      management strategies for PCP.

PMID- 19403209
TI  - [Use of a fast influenza antigen test does not decrease prescription of
      antibiotics].

PMID- 19403211
TI  - [Non-Hodgkin's lymphoma and pustular psoriasis: a case report].
AB  - Psoriasis has been hypothesized to be associated with lymphoma. Several studies
      demonstrated an epidemiological relationship between these two entities. Patients
      with psoriasis are at increased risk for developing lymphoproliferative
      malignancies. This risk can be also the consequence of immunosuppressive
      therapies (methotrexate or cyclosporine). We report a 65-year-old man who
      presented with diffuse erythematous plaques with pustular or squamous borders.
      Histopathologic evaluation concluded to a pustular psoriasis. We discover
      simultaneously a stage 4 bone marrow B lymphoma of low grade of malignancy. This
      case report highlights the relationships between psoriasis and lymphoma.

PMID- 19403210
TI  - Synthesis, antimalarial evaluation and molecular modeling studies of
      hydroxyethylpiperazines, potential aspartyl protease inhibitors, part 2.
AB  - The antimalarial acitivity of hydroxyethylamines, synthesized from the reaction
      of intermediated hydroxyethypiperazines with benzenesulfonyl chlorides or benzoyl
      chlorides, has been evaluated in vitro against a W2 Plasmodium falciparum clone.
      Some of the nineteen tested derivatives showed a significant activity in vitro,
      thus turning into a promising new class of antimalarials. In addition, a
      molecular modeling study of the most active derivative (5l) was performed and its
      most probable binding modes within plasmepsin II enzyme were identified.

PMID- 19403212
TI  - Feeding in acute pancreatitis -- avoiding the enteralist dogma.

PMID- 19403213
TI  - Modeling of the EMRAS urban working group hypothetical scenario using the RESRAD
      RDD methodology.
AB  - The RESRAD-RDD methodology was applied to model the short- and long-term
      radiation exposures after a hypothetical radiological dispersal device (RDD)
      event in an urban environment. It was assumed that an RDD event would result in
      outside surface contamination of the exterior walls and roofs of surrounding
      buildings, as well as associated paved areas and lawns. The contaminants also
      might move inside the buildings and deposit on floors and interior walls. Some
      important input parameters include occupancy factors, building characteristics,
      and weathering of surface contamination. The modeling results include predicted
      external dose rates, relative contributions from important surfaces, annual and
      cumulative doses, and radionuclide concentrations. Potential countermeasures
      evaluated include grass removal, soil removal, and washing of paved areas.

PMID- 19403214
TI  - Increased environmental gamma-ray dose rate during precipitation: a strong
      correlation with contributing air mass.
AB  - It has long been observed that the environmental gamma-ray dose rate increases
      noticeably during precipitation intervals. This increase, due to the presence of
      radon progeny in the rain droplets (or snow flakes), can affect the reliability
      of the monitoring of artificial radioactivity and long term estimates of exposure
      to ambient natural radionuclides in surveillance network. Predicting the
      amplitude of the dose increase has been shown to be surprisingly challenging. In
      this work, standard air mass back trajectory analysis is used to show that the
      amplitude of the increase can be quantitatively linked to the history of the air
      mass where the precipitation is occurring. Furthermore, we show how back
      trajectory analysis, environmental gamma and rain data can be used to obtain
      estimations of relative radon emanation rates for locations far from the actual
      point of detection.

PMID- 19403216
TI  - Gray's Reinforcement Sensitivity Theory as a framework for research on
      personality-psychopathology associations.
AB  - Gray's Reinforcement Sensitivity Theory (RST) presupposes individual differences
      in the sensitivity of basic brain systems that respond to punishing and
      reinforcing stimuli. These differences are thought to underlie the personality
      dimensions of anxiety and impulsivity, and to have relevance for psychopathology.
      The present article aims at reviewing RST-based research on personality
      psychopathology associations. First, RST and its revisions are described and the
      link between RST systems and personality dimensions is discussed. Second, studies
      investigating associations between RST systems and specific types of
      psychopathology are summarized. Although the available research yields a rather
      consistent picture with respect to constellations of BIS/BAS sensitivity that are
      associated with specific types of psychopathology, it also provides a clear
      indication that much work remains to be done. The discussion section highlights
      several topics that deserve future research attention.

PMID- 19403215
TI  - Internet-based interventions for traumatic stress-related mental health problems:
      a review and suggestion for future research.
AB  - Exposure to potentially traumatic events is a common occurrence. Most individuals
      exposed to such an event are resilient or recover rapidly, although some
      individuals develop psychological problems that warrant treatment. However, a
      small percentage of individuals seek traditional treatment, thereby calling for
      novel approaches or methodologies of treatment. The present paper provides a
      comprehensive and critical review of the extant literature on computerized and
      internet-based interventions (IBIs) for traumatic stress-related conditions
      (i.e., panic disorder, posttraumatic stress disorder/complicated grief,
      depression, comorbid anxiety and depression, alcohol abuse, smoking cessation).
      Generally, computerized or IBIs for depression and anxiety are yielding effect
      sizes that are comparable to traditional psychosocial treatment. Interventions
      aimed at alcohol and smoking cessation generally have lower effect sizes than do
      IBIs for anxiety and depression. Most interventions reviewed in this paper
      included common components (e.g., were developed through a cognitive behavioral
      framework and included psychoeducation, cognitive restructuring, goal setting,
      exposure). Therefore, it is possible that these shared features may in part
      account for symptom reduction. Little is known regarding mechanisms of change.
      Future directions for novel web-based approaches to treatment are provided.

PMID- 19403217
TI  - Looking for resilience: understanding the longitudinal trajectories of responses
      to stress.
AB  - Taking advantage of two large, population-based, and longitudinal datasets
      collected after the 1999 floods in Mexico (n=561) and the September 11, 2001
      terrorist attacks in New York (n=1267), we examined the notion that resilience
      may be best understood and measured as one member of a set of trajectories that
      may follow exposure to trauma or severe stress. We hypothesized that resistance,
      resilience, recovery, relapsing/remitting, delayed dysfunction, and chronic
      dysfunction trajectories were all possible in the aftermath of major disasters.
      Semi-parametric group-based modeling yielded the strongest evidence for
      resistance (no or mild and stable symptoms), resilience (initially moderate or
      severe symptoms followed by a sharp decrease), recovery (initially moderate or
      severe symptoms followed by a gradual decrease), and chronic dysfunction
      (moderate or severe and stable symptoms), as these trajectories were prevalent in
      both samples. Neither Mexico nor New York showed a relapsing/remitting
      trajectory, and only New York showed a delayed dysfunction trajectory.
      Understanding patterns of psychological distress over time may present
      opportunities for interventions that aim to increase resilience, and decrease
      more adverse trajectories, after mass traumatic events.

PMID- 19403218
TI  - Cognitive conflict and inhibition in primed dichotic listening.
AB  - In previous behavioral studies, a prime syllable was presented just prior to a
      dichotic syllable pair, with instructions to ignore the prime and report one
      syllable from the dichotic pair. When the prime matched one of the syllables in
      the dichotic pair, response selection was biased towards selecting the unprimed
      target. The suggested mechanism was that the prime was inhibited to reduce
      conflict between task-irrelevant prime processing and task-relevant dichotic
      target processing, and a residual effect of the prime inhibition biased the
      resolution of the conflict between the two targets. The current experiment
      repeated the primed dichotic listening task in an event-related fMRI setting. The
      fMRI data showed that when the task-irrelevant prime matched the task-relevant
      targets, activations in posterior medial frontal cortex (pMFC) and in right
      inferior frontal gyrus (IFG) increased, which was considered to represent
      conflict and inhibition, respectively. Further, matching trials where the
      unprimed target was selected showed activation in right IFG, while matching
      trials where the primed target was selected showed activations in pMFC and left
      IFG, indicating the difference between inhibition-biased selection and unbiased
      selection.

PMID- 19403219
TI  - [Pulmonary abscess due to Leuconostoc species in an immunocompetent patient].

PMID- 19403220
TI  - [Bilateral pneumothorax after pleural drainage].

PMID- 19403221
TI  - [A new case of idiopathic bronchiolocentric interstitial pneumonia].

PMID- 19403222
TI  - [Inflammatory cytokines and repair factors in the intercostal muscles of patients
      with severe COPD].
AB  - OBJECTIVE: There is disagreement regarding the local action of cytokines in the
      respiratory muscles of patients with chronic obstructive pulmonary disease
      (COPD). The objective of this study was to analyze the relationships between
      cytokine expression and genetic activation of the mechanisms of muscle repair.
      PATIENTS AND METHODS: Twenty-five patients with severe COPD and in stable
      condition were enrolled in the study. We performed a biopsy of the external
      intercostal muscle of the patients and analyzed the specimen for signs of muscle
      lesion (morphometry), infiltration of inflammatory cells (immunohistochemistry),
      and expression of selected genes (real-time polymerase chain reaction technique)
      corresponding to the cytokines (tumor necrosis factor alpha [TNF-alpha] and its
      type 1 and 2 receptors [TNFR1 and TNFR2], and interleukin [IL] 1beta, IL-6, and
      IL-10), a pan-leukocyte marker (CD18), and key molecules in the repair-myogenesis
      pathways (Pax7, M-cadherin, and MyoD). RESULTS: Expression of TNFR2 is directly
      related to inspiratory muscle function (represented by maximum sustainable
      inspiratory pressure; r=0.496; P<.05), whereas expression of CD18 is inversely
      related (r=0.462; P<.05). Moreover, expression of the 2 TNF-alpha receptors was
      directly related to that of the key molecules of the repair pathways analyzed
      (TNFR1 to Pax7 [r=0.650; P<.001] and M-cadherin [r=0.678; P<.001]; TNFR2 to Pax7
      [r=0.395; P<.05], M-cadherin [r=0.409; P<.05], and MyoD [r=0.418; P<.05]).
      CONCLUSIONS: Expression of TNF-alpha receptors bears a close relationship both to
      activation of the myogenesis programs and to inspiratory muscle function. This
      reinforces our hypothesis that some local cytokines take part in the repair of
      respiratory muscles in patients with COPD.

PMID- 19403223
TI  - [Prone position for the treatment of acute respiratory distress syndrome: a
      review of current literature].
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) have high
      incidence and mortality rates. Most of the recently introduced treatments have
      failed to improve the prognosis of patients with ALI or ARDS or to reduce
      mortality. Several studies have shown improved oxygenation in the prone position
      during mechanical ventilation in patients with ARDS. However, current evidence
      strongly suggests that placing ARDS patients in prone position does not improve
      survival or reduce the duration of mechanical ventilation. Therefore, though in
      clinical practice this position may improve refractory hypoxemia in patients with
      ARDS, there is no evidence to support its systematic use.

PMID- 19403224
TI  - [Pulmonary epithelioid hemangioendothelioma].
AB  - Epithelioid hemangioendothelioma is a multifocal tumor that rarely metastasizes.
      It is difficult to diagnose and is most often an incidental finding in young
      asymptomatic women. It has a heterogeneous radiologic pattern. The most important
      diagnostic information is histologic confirmation of Weibel-Palade bodies or
      immunohistochemistry based on specific tumor markers such as factor VIII and
      CD34. We report the case of a 73-year-old woman in whom multiple pulmonary
      nodules detected by chance in a radiograph were subsequently diagnosed as
      epithelioid hemangioendothelioma.

PMID- 19403225
TI  - [Treatment of catamenial pneumothorax with diaphragmatic defects].

PMID- 19403226
TI  - [Tracheal mucormycosis].

PMID- 19403227
TI  - [Acute transient ataxia caused by local lidocaine injection during insertion of a
      pleural catheter].

PMID- 19403228
TI  - Effect of sodium, amine and stannous fluoride at the same concentration and
      different pH on in vitro erosion.
AB  - OBJECTIVE: This study aimed to compare the effects 0.5% and 1% sodium, amine and
      stannous fluoride at different pH on enamel erosion in vitro. METHODS: Bovine
      enamel samples were submitted to a cyclic de- and remineralisation for 3 days.
      Each day, the samples were exposed for 120 min to pooled human saliva and
      subsequently treated with one of the fluoride solutions for 3 min: amine fluoride
      (AmF, 0.5% and 1% F(-)), sodium fluoride (NaF, 0.5% and 1% F(-)), each at pH 3.9
      and 7.0, and stannous fluoride (SnF(2), 0.5% and 1% F(-)), at pH: 3.9.
      Additionally, two groups were treated with fluoride-free placebo solutions (pH:
      3.9 and 7.0) and one group served as control (no fluoridation). Ten specimens
      each group were inserted in a so-called artificial mouth and eroded six times
      daily with hydrochloric acid (pH 2.6) for 90 s each intermitted by exposure to
      artificial saliva (1h). After 3 days, enamel loss was analyzed profilometrically
      and evaluated statistically by ANOVA. RESULTS: Only the acidic 0.5% and 1% SnF(2)
      and 1% AmF solutions were able to reduce erosive enamel loss significantly, while
      all other solutions and placebos did not differ significantly from the control.
      Between the acidic SnF(2) and the 1% AmF solutions no significant differences
      could be detected. CONCLUSION: At the same concentrations, acidic SnF(2) and AmF
      may be more effective than NaF to protect enamel against erosion.

PMID- 19403229
TI  - The effect of casein and calcium containing paste on plaque pH following a
      subsequent carbohydrate challenge.
AB  - OBJECTIVES: Previous research has shown that regular use of CPP-ACP increases
      calcium and inorganic phosphates in plaque and reduces enamel mineral loss. The
      aim of this study was to investigate if a CPP-ACP-containing paste would
      neutralize acidic challenges in dental plaque following sucrose rinse. METHOD:
      Plaque pH was measured on 15 subjects in a cross-over study with and without
      prior application of the paste and with and without CPP-ACP. On each occasion,
      subjects rinsed with 10% sucrose and sorbitol solutions for 2 min in randomized
      order. RESULTS: The results showed the median lowest pH without paste was 4.8
      (IQR: 4.7-5.0) and with mousse 5.6 (IQR: 5.5-5.6 and p<0.001). The median lowest
      pH was 5.0 (IQR: 4.9-5.3) without CPP-ACP and with CPP-ACP was 5.8 (5.6-6.1 and
      p<0.001). The time that pH remained below 5.7 and the time to return to resting
      pH showed similar differences in all subjects (p<0.01). CONCLUSION: The results
      indicate that prior application of a CPP-ACP-containing paste reduced the fall in
      plaque pH following a sucrose challenge.

PMID- 19403230
TI  - Effect of different adhesive systems and laser treatment on the shear bond
      strength of bleached enamel.
AB  - PURPOSE: This study determined the shear bond strength of a nanohybrid composite
      resin to bleached enamel immediately or 15 days later using different adhesive
      systems and laser application. METHODS: One hundred and forty enamel specimens
      were prepared from human molar teeth and bleached either with 16% carbamide
      peroxide (CP) or 30% CP according to the manufacturer's (Vivastyle/Vivadent)
      recommendations. After bleaching treatments specimens were divided into two
      groups according to the treatment time of the adhesive procedures: immediately or
      15 days after the bleaching treatments. The four groups were then divided into
      five subgroups due to the surface treatments: using a two-step self-etching
      adhesive (AdheSe, Ivoclar Vivadent G, Schaan, Liechtenstein) or a two-step etch
      and rinse adhesive (Excite, Ivoclar Vivadent G, Schaan, Liechtenstein) and
      application of laser prior to adhesive procedures or not. After adhesive
      procedures nanohybrid composite resin cylinders of 4 mm x 2 mm (Tetric Evo
      Ceram/Vivadent) were bonded to the enamel surfaces. All specimens were subjected
      to shear bond strength test after thermocycling and 24h of storage in water. Data
      were analyzed statistically. RESULTS: Mann-Whitney U-test analysis showed no
      significant difference in the mean bond strength values of enamel bleached with
      either 16% CP or 30% CP (p>0.05). There was no difference between the groups
      bonded immediately or 15 days after bleaching (p>0.05). Application of the etch
      and rinse adhesive after 15 days showed the highest bond strength values, whereas
      self-etching adhesive and laser application showed the lowest values in both
      bleaching treatments. CONCLUSIONS: The results suggested that following the
      bleaching treatments, the use of etch and rinse adhesive system may provide
      higher bond strengths than self-etching adhesive and laser application.

PMID- 19403231
TI  - The effect of two different counting methods on the quality of CPR on a manikin-
      a randomized controlled trial.
AB  - OBJECTIVES: To compare the quality of cardiopulmonary resuscitation (CPR) and
      rescuers' exhaustion using different methods of counting, and to establish an
      appropriate method of counting. MATERIALS AND METHODS: Forty-eight subjects who
      had received formal training in basic life support (BLS) were recruited from
      doctors and nurses working in the Emergency Department of a university hospital.
      They performed 3 min of continuous chest compressions using two different methods
      of counting, one after the other, on an adult resuscitation manikin. The total
      number of compressions, the number of these considered satisfactory, the peak
      heart rate of subjects and the time to peak heart rate were all recorded.
      Perceived fatigue and discomfort was evaluated by self-reported survey results
      with use of a visual analogue scale (VAS). RESULTS: The effective power of
      external chest compression and the mean compression depth when counting from 1 to
      10, repeated three times, were greater than those achieved when counting from 1
      to 30 during 3 min of CPR (67.48% vs. 57.81% and 44.52 mm vs. 40.48 mm, P<0.05).
      The exhaustion-score using the VAS (22.15 points) was lower and the time to peak
      heart rate (124.88 s) was longer when counting from 1 to 10, repeated three
      times, than when rescuers counted from 1 to 30. CONCLUSIONS: Counting from 1 to
      10 three times in Chinese as opposed to 1-30 results in better quality chest
      compressions. Counting from 1 to 10 three times was associated with less user
      feelings of fatigue, and a longer time to peak heart rate. These findings support
      the teaching of counting compressions 1-10 three times during CPR.

PMID- 19403232
TI  - Depth of sternal compression and intra-arterial blood pressure during CPR in
      infants following cardiac surgery.
AB  - The optimal depth of sternal compressions during cardiopulmonary resuscitation
      (CPR) in infants is unknown; current guidelines recommend compressing to a depth
      of 1/3rd to 1/2 the anterior-posterior (AP) diameter of the chest. Our experience
      to compress the chest at 1/3rd the AP diameter often fails to provide an adequate
      blood pressure response. We reviewed our experience with CPR, depth of
      compressions, and arterial blood pressure response in a cohort of 6 infants
      having cardiac surgery and subsequent cardiac arrest. Pediatric advanced life
      support measures were initiated, with attempted compressions to 1/3rd the AP
      chest diameter. Depth of attempted compressions was increased to approximately
      1/2 the AP chest diameter if systolic BP response was inadequate (i.e., <60mm Hg
      systolic). BP tracings were reviewed and contiguous recordings were evaluated as
      compressions were attempted at 1/3rd and 1/2 the AP chest diameter. The age range
      was from 2 weeks to 7.3 months, and median age was of 1.0 month. The mean
      systolic BP was 83.4mm Hg for the 1/2 AP chest diameter technique vs. 51.6mm Hg
      for the 1/3rd AP diameter approach, p<0.001. The mean diastolic pressure was
      similar with both strategies (30.5 vs. 30.6mm Hg, p=0.99). In this cohort of 6
      infants having cardiac surgery and subsequent cardiac arrest, attempting to
      compress the chest at 1/2 the AP diameter increased systolic blood pressure by
      62% compared to attempting to compress 1/3rd the AP diameter. Perhaps
      resuscitators should attempt to compress infants' chests 1/2 rather than 1/3rd
      the AP diameter of the chest.

PMID- 19403233
TI  - Prematuration of bovine oocytes with butyrolactone I reversibly arrests meiosis
      without increasing meiotic abnormalities after in vitro maturation.
AB  - OBJECTIVES: Asynchrony between nuclear and cytoplasmic maturation, and possibly
      damage to the oocyte meiotic spindle, limits the application of in vitro
      maturation (IVM) in assisted reproduction. Several studies have suggested that
      Prematuration with meiosis blockers may improve oocyte quality after IVM,
      favoring early embryogenesis. Thus, we investigated the effect of Prematuration
      with the nuclear maturation inhibitor butyrolactone I (BLI) on the meiotic
      spindle and chromosomal configuration of bovine oocytes. STUDY DESIGN: Immature
      oocytes obtained from cows slaughtered in a slaughterhouse (n=840) were divided
      into the following groups: (1) control (n=325), submitted only to IVM in TCM199
      for 24h; (2) BLI 18h (n=208) submitted to meiotic blockage with 100 microM BLI
      for 24h (Prematuration) and then induction of IVM in TCM199 for 18h; and (3) BLI
      24h (n=307), pre-matured with 100 microM BLI for 24h followed by 24h of IVM in
      TCM199. The oocytes were then fixed, stained by immunofluorescence for
      morphological visualization of both microtubules and chromatin, and evaluated.
      RESULTS: Meiotic arrest occurred in 90.2% of the oocytes cultured with BLI.
      Maturation rates were similar for all groups (80.3%, 73.6% and 82.7% for the
      control, BLI 18h and BLI 24h groups, respectively). We observed 81.3% normal
      oocytes in metaphase II in the control group, and 80.0% and 81.2% in the BLI 18h
      and BLI 24h groups, respectively. The incidence of meiotic anomalies did not
      differ between groups (18.7%, 20.0% and 18.8% for the control, BLI 18h and BLI
      24h, respectively). CONCLUSION: Prematuration with butyrolactone I reversibly
      arrests meiosis without damaging the meiotic spindle or the chromosome
      distribution of bovine oocytes after in vitro maturation.

PMID- 19403234
TI  - Intrinsic noise in post-transcriptional gene regulation by small non-coding RNA.
AB  - Small non-coding RNA (sRNA) plays very important role in the post transcriptional
      regulation in various organisms. In complex regulatory networks, highly
      significant relative fluctuations in RNAs copy numbers can not be neglected due
      to very small copy number of individual RNA molecules. Here we consider two
      simple regulation schemes, where one is single target gene regulated by a sRNA
      and the other is two target mRNAs (mRNA(R) and mRNA(T)) regulated by one sRNA.
      The Fano factor (a measure of the relative size of the internal fluctuations)
      formulae of RNA molecules in the post transcriptional regulation are
      theoretically derived by using of the Langevin theory. For single target gene
      regulated by a sRNA, it is shown that the intrinsic noise of both mRNA and sRNA
      approaches the bare Poissonian limit in the regimen of both target RNA silencing
      and surviving. However, the strong anti-correlation between the fluctuations of
      two components result in a large intrinsic fluctuations in the level of RNA
      molecules in the regimen of crossover. For two target mRNAs regulated by one
      sRNA, in the regimen of crossover, it is found that, with the increasing of
      transcription rate of target mRNA(T), the maximal intrinsic fluctuation of RNA
      molecules is shifted from sRNA to target mRNA(R), and then to target mRNA(T). The
      intrinsic noise intensity of target mRNA(R) is determined by both the
      transcriptional rate of itself and that of sRNA, and independent of the
      transcriptional rate of the other target mRNA(T).

PMID- 19403235
TI  - EAU guidelines on neurogenic lower urinary tract dysfunction.
AB  - CONTEXT: Most patients with neurogenic lower urinary tract dysfunction (NLUTD)
      require life-long care to maintain their quality of life (QoL) and to maximise
      life expectancy. OBJECTIVE: To provide a summary of the 2008 version of the
      European Association of Urology (EAU) guidelines on NLUTD and to assess the
      effectiveness of currently available diagnostic tools, particularly ultrasound
      imaging and urodynamics. EVIDENCE ACQUISITION: The recommendations provided in
      the 2008 EAU guidelines on NLUTD are based on a review of the literature, using
      online searches of Medline and other source documents published between 2004 and
      2007. A level of evidence and/or a grade of recommendation have been assigned to
      the guidelines where possible. EVIDENCE SYNTHESIS: NLUTD encompasses a wide
      spectrum of pathologies, and patients often require life-long, intensive medical
      care to maximise their life-expectancy and to maintain their QoL. Treatment must
      be tailored to the needs of the individual patient and, in many cases, involves a
      multidisciplinary team of experts. Timely diagnosis and treatment are essential
      if irreversible deterioration of both the upper and lower urinary tracts are to
      be avoided. Therapeutic decisions are made on the basis of a comprehensive
      medical assessment, including urodynamics to identify the type of dysfunction.
      Advances in investigative technologies have facilitated the noninvasive and
      conservative management of patients who have NLUTD. CONCLUSIONS: The diagnosis
      and treatment of NLUTD, which is a highly specialised and complex field involving
      both urology and medicine, requires up-to-date expert advice to be readily
      available. The current guidelines are designed to fulfil this need.

PMID- 19403236
TI  - Vattikuti Institute prostatectomy: technical modifications in 2009.
AB  - BACKGROUND: Since we last published our technique of robotic prostatectomy, we
      have introduced three technical refinements: superveil nerve sparing, bladder
      drainage with a percutaneous suprapubic tube (PST), and limited node dissection
      of the obturator and internal iliac nodes in preference to the external iliac
      nodes in selected patients. OBJECTIVE: To describe selection criteria, to explain
      the three techniques, and to evaluate functional and oncologic results. DESIGN,
      SETTING, AND PARTICIPANTS: Single-institution study of 1151 radical
      prostatectomies performed from 2006 to 2008 by one surgeon. SURGICAL PROCEDURE:
      The superveil nerve-sparing technique spares nerves from the 11-o'clock position
      to the 1-o'clock position. The bladder is drained with a PST rather than a
      urethral catheter. For low- or intermediate-risk disease, limited lymphadenectomy
      concentrates on the internal iliac and obturator nodes, excluding the external
      iliac lymph nodes. MEASUREMENTS: Erectile function and patient comfort were
      evaluated using questionnaires administered by a third party. Lymph node yield
      was quantified by a qualified uropathologist. RESULTS AND LIMITATIONS: At 6-18
      months after surgery, 94% of men who attempted sexual intercourse were successful
      with a median Sexual Health Inventory For Men (SHIM) score of 18 out of 25. PST
      bladder drainage resulted in less patient discomfort; visual analog scores were 2
      at 2 days after prostatectomy and 0 at 6 days after prostatectomy. The modified
      lymphadenectomy harvested few overall nodes, but it increased the yield of
      positive nodes >13-fold in patients with low-risk stratification (6.7% compared
      with 0.5%). CONCLUSION: In this single-institution, single-surgeon study, these
      modifications improved erectile function outcomes, decreased catheter-associated
      discomfort, and enhanced the detection of positive nodes.

PMID- 19403237
TI  - Removal of some heavy metal cations by synthetic resin purolite C100.
AB  - The discharge of heavy metals into aquatic ecosystems has become a matter of
      concern over the last few decades. These pollutants are introduced into the
      aquatic systems significantly as a result of various industrial operations. This
      paper describes the adsorption behaviour of cation exchange resin purolite C100
      with respect to Ce(4+), Fe(3+) and Pb(2+) in order to consider its application to
      purify metal finishing wastewaters. The batch method has been employed, using
      metal concentrations in solution ranging from 2.65 to 265mg/L. The adsorption
      percentages (%) and distribution coefficient (K(d)) were determined for the
      adsorption system in the aqueous media as a function of sorbate concentration.
      The experimental isotherm data were analyzed using the Langmuir, Freundlich, and
      Dubinin-Kaganer-Radushkevich (DKR) equations. It was found that the adsorption
      phenomena depend on charge density and hydrated ion diameter. According to the
      equilibrium studies, the metal ions sequence can be given as
      Ce(4+)>Fe(3+)>Pb(2+). These results show that cation exchange resin purolite C100
      holds great potential to remove cationic heavy metal species from polluted
      wastewater.

PMID- 19403238
TI  - Removal of chlorophenols in aqueous solution by carbon black low-cost adsorbents.
      Equilibrium study and influence of operation conditions.
AB  - The adsorption process of chlorophenols (CPs) by low-cost adsorbents such as
      carbon blacks has been studied. The influence of different parameters such as
      temperature, pH, ionic strength and textural properties of the adsorbents on the
      adsorption process of pentachlorophenol has been analyzed. The adsorption process
      is exothermal and parameters such as pH and ionic strength exert a noticeable
      influence on the adsorption capacity of the solute. These parameters influence
      the adsorption capacity in an opposite manner. Thus an increase in pH seems to
      unfavor the adsorption process, whereas the adsorption capacity increases with
      increasing ionic strength. In order to analyze the influence of the number of
      chlorine atoms in the molecule of solute the adsorption process of different
      chlorophenols (i.e., 4-chlorophenol, 3,5-dichlorophenol, 2,4,6-trichlorophenol
      and 2,3,4,6-tetrachlorophenol) was analyzed. As the number of chlorine atoms (and
      thus the volume of the molecule) increases, the penetration of the solute through
      the porous texture of the adsorbent is difficult and, consequently, the
      adsorption capacity decreases.

PMID- 19403239
TI  - Emerging arthropod-borne diseases of companion animals in Europe.
AB  - Vector-borne diseases are caused by parasites, bacteria or viruses transmitted by
      the bite of hematophagous arthropods (mainly ticks and mosquitoes). The past few
      years have seen the emergence of new diseases, or re-emergence of existing ones,
      usually with changes in their epidemiology (i.e. geographical distribution,
      prevalence, and pathogenicity). The frequency of some vector-borne diseases of
      pets is increasing in Europe, i.e. canine babesiosis, granulocytic anaplasmosis,
      canine monocytic ehrlichiosis, thrombocytic anaplasmosis, and leishmaniosis.
      Except for the last, these diseases are transmitted by ticks. Both the
      distribution and abundance of the three main tick species, Rhipicephalus
      sanguineus, Dermacentor reticulatus and Ixodes ricinus are changing. The
      conditions for such changes involve primarily human factors, such as travel with
      pets, changes in human habitats, social and leisure activities, but climate
      changes also have a direct impact on arthropod vectors (abundance, geographical
      distribution, and vectorial capacity). Besides the most known diseases, attention
      should be kept on tick-borne encephalitis, which seems to be increasing in
      western Europe, as well as flea-borne diseases like the flea-transmitted
      rickettsiosis. Here, after consideration of the main reasons for changes in tick
      vector ecology, an overview of each "emerging" vector-borne diseases of pets is
      presented.

PMID- 19403240
TI  - Calcium sulfide (CaS), a donor of hydrogen sulfide (H(2)S): a new
      antihypertensive drug?
AB  - Hypertension is the leading cause of cardiovascular diseases, and an estimated
      972 million people in the world are suffering from this problem. Indubitably,
      hypertension is an important worldwide public-health challenge. In recent years
      many efforts have been made to devise novel therapies involving new targets
      implicated in cardiovascular diseases. Hydrogen sulfide (H(2)S) is a member of a
      growing family of "gasotransmitters". It is clear that H(2)S plays a pivotal role
      in the basal regulation of vessels tone. Also studies demonstrate that
      intravenous sodium hydrosulfide (NaHS), a donor of H(2)S, dose-dependently
      decreases systolic blood pressure. However, because of its active chemical
      property, NaHS can be easily oxidized, even spontaneously ignited in the open
      air. Moreover, its solution is not stable. So the pharmacal use of NaHS is
      limited by its properties. Calcium sulfide (CaS), one of the effective components
      in a traditional herb, is another donor of H(2)S. It has more stable chemical
      properties than NaHS. We hypotheses that CaS might be given by mouth as a new
      antihypertensive drug through certain dosage form designing. To test this
      hypothesis, we should establish animal models for studies including drug
      efficacy, drug safety, drug toxicology, drug metabolism and drug kinetics.

PMID- 19403241
TI  - Slow zoledronic acid releasing testis prostheses in the treatment of prostate
      cancer patients with bone metastases.
AB  - Surgical castration is still considered the 'gold standard' for androgen
      deprivation therapy which have become the mainstay for the management of advanced
      prostate cancer. The main drawback of this safe operation is that it may have a
      negative psychological effect, thus, in recent years, a decline in the
      utilization of bilateral orchiectomy which is the most cost-effective form of
      androgen deprivation therapy can be witnessed. Testicular prostheses have been
      shown to reduce the psychological impact resulting from loss or absence of a
      testicle in those patients. Besides, patients with advanced prostate cancer are
      at risk of skeletal complications and bisphosphonates are used in treatment.
      Zoledronic acid is the only bisphosphonate agent demonstrated to effectively
      reduce skeletal related events in patients with advanced prostate cancer
      metastatic to bone. Therefore, zoledronic acid releasing testicular prostheses
      can be used in the treatment of prostate cancer patients with bone metastases
      after bilateral orchiectomy. This technology has the potential to become the
      preferred clinical management tool for prostate cancer patients with bone
      metasthases after bilateral orchiectomy.

PMID- 19403242
TI  - [TVT Secur: prospective study and follow up at 1 year about 154 patients].
AB  - OBJECTIVES: To evaluate the efficacy and complications of this new sub-urethral
      tape procedure with a follow up of 12 months. MATERIALS AND METHODS: Prospective,
      multicenter study of 154 patients operated for stress urinary incontinence with
      the TVT Secur. Patients were operated between 24 July 2006 and 18 December 2007
      and were all controlled at 2 months and 118 at 1 year. No associated surgical
      procedure was performed. RESULTS: One hundred five patients had pure stress
      incontinence with 12 of them presenting an intrinsic sphincter deficient. Forty
      nine had a mixed urinary incontinence with 12 of them having ISD. Preoperatively,
      69 patients complained of urgency and 12 of micturation disorder. Anaesthesia was
      local for 97 patients (63%). Per operative complications were five hemorrhages,
      one bladder injury, one vaginal wound, 21 patients had post-void residual volume
      (100 to 200ml) and one groin pain. We noted two exposed tapes, one granuloma, one
      ITU and seven lateral vaginal bands. Among the patients with urge at baseline,
      61.2% were cured at 2 months and 75.5% at 1 year. De novo urge appeared in 12.8%
      at 2 months and 12.3% at 1 year. De novo micturation disorder was found in 9.5%
      at 2 months and 3.7% at 1 year. The cured patients at 1 year were 70.3%, improved
      11% and fails 18.7%. The cured rate remains same between 2 months and 1 year. The
      improved patients (24%) at 2 months remain 11% at 1 year. The recurrence rate was
      12,8% at 1 year. CONCLUSION: The results are inferior to TVT or TVT-O procedures.
      We probably must selected the patients for this procedure.

PMID- 19403243
TI  - Open-label dose-finding trial of buprenorphine implants (Probuphine) for
      treatment of heroin dependence.
AB  - Buprenorphine, a mu-opioid receptor partial agonist, has been shown to be safe
      and effective for treatment of opioid dependence. A novel implantable formulation
      of buprenorphine (Probuphine), using a polymer matrix sustained-release
      technology, has been developed to offer treatment for opioid dependence while
      minimizing risks of patient noncompliance and illicit diversion. The goal of the
      current study was to conduct an initial, open-label, evaluation of the safety,
      pharmacokinetics, and efficacy of two doses of Probuphine in subjects with opioid
      dependence maintained on sublingual buprenorphine. Two doses of Probuphine were
      evaluated in 12 heroin-dependent volunteers switched from daily sublingual
      buprenorphine dosing to either two or four Probuphine implants based upon their
      buprenorphine daily maintenance dose of 8 mg or 16 mg respectively, and were
      monitored for 6 months. Probuphine implants provided continuous steady state
      delivery of buprenorphine until their removal at 6 months. Withdrawal symptoms
      and craving remained low throughout the 6 months. For the 12 subjects, an average
      of 59% of urines were opioid-negative across the 6 month treatment period.
      Injection site reactions were present in half of patients, but none were serious.
      No safety concerns were evident. These results suggest that Probuphine implants
      offer significant promise for enhancing delivery of effective opioid substitution
      treatment while minimizing risk for abuse of medication.

PMID- 19403244
TI  - Diagnosis by culture and PCR of Salmonella abortusovis infection under clinical
      conditions in aborting sheep in Switzerland.
AB  - Since 2003 eleven Swiss sheep flocks were affected by abortion storms due to
      Salmonella abortusovis, an infection which had not been reported in this country
      for decades although cases of salmonellosis are notifiable in Switzerland. This
      raised doubts about the adequacy of the currently used diagnostic tools and the
      origin of this infection. Therefore, PCR was tested for its potential as a more
      rapid and more reliable method for diagnosing S. abortusovis infections under
      field conditions. Fecal and vaginal samples were collected at different times
      after abortion and PCR was used to detect bacterial DNA. Bacteria were isolated
      by conventional culture techniques. For determining their origin they were
      analyzed by pulsed field gel electrophoresis (PFGE) and compared to isolates from
      Germany and France. Sequencing of randomly selected amplicons allowed confirming
      the specificity of the result. PCR was more sensitive because it allowed
      detecting S. abortusovis DNA up to three months after infection even in samples
      that were negative by culture. Escherichia coli from the digestive tract of sheep
      could inhibit the growth of S. abortusovis in vitro suggesting that the lower
      sensitivity of diagnosis by bacterial culture may in part be due to growth
      inhibition of S. abortusovis by resident bacteria. Results of PFGE indicated that
      the Swiss strains were closely related among themselves but distinct from German
      and French strains suggesting the presence of an autochthonous infection.

PMID- 19403245
TI  - Pilot use of the early motor repertoire in infants with inborn errors of
      metabolism: outcomes in early and middle childhood.
AB  - BACKGROUND: Predicting later outcome in neonates presenting with severe inborn
      errors of metabolism (IEM) is difficult. The assessment of the early motor
      repertoire is a reliable method of evaluating the integrity of the central
      nervous system in young infants. This method is based on an age-specific
      qualitative assessment of general movements (GMs, 0-8 weeks of age), fidgety
      movements (FMs) and the concurrent motor repertoire (9-20 weeks of age). AIM: To
      determine the quality of the early motor repertoire (at 0-20 weeks post term age)
      in relation to later neurological outcome in infants with severe IEM. STUDY
      DESIGN: Prospective cohort study. The quality of the motor repertoire was
      assessed from serial videotape recordings. SUBJECTS: Five infants with IEM. Four
      presented with a severe IEM in the neonatal period: an undefined gluconeogenesis
      defect, propionic acidemia, arginosuccinate synthetase and arginosuccinate lyase
      deficiency. One neonate was antenatally diagnosed with arginosuccinate synthetase
      deficiency. OUTCOME MEASURES: Outcome at the age of at least 18 m was determined
      by neurological examination and developmental tests. RESULTS: All infants
      initially had abnormal GMs: hypokinesia, followed by GMs of a poor repertoire.
      The quality of the early motor repertoire normalised in 3 infants, and remained
      abnormal in 2. The more severe and persistent abnormalities of the motor
      repertoire were considered with the more abnormal neurological and developmental
      scores, later on. CONCLUSIONS: The quality of the early motor repertoire might be
      related to later neurological outcome in infants with inborn errors of
      metabolism.

PMID- 19403246
TI  - Risk factors for cardiovascular disease in women.
AB  - Management of women's health seldom includes cardiovascular disease (CVD)
      prevention in spite of CVD being the most common cause of death in females being
      even more common than cancer, HIV/AIDS, malaria and tuberculosis combined.
      According to the World Heart Federation, CVD is indisputably the most serious,
      neglected health problem for women in both the developing and the developed
      worlds. A possible reason may be that CVD has traditionally been perceived as a
      'man's illness'. Since 6 out of 10 deaths from CVD can be prevented, it is of
      utmost importance that there is more general awareness about CVD in women. The
      most important factors for developing CVD are dyslipidaemia, hypertension,
      smoking, stress, diabetes, obesity (especially abdominal fat distribution),
      physical inactivity, poor eating habits and possibly excessive alcohol intake.
      Some unique risk factors for CVD exist in women; of which older age at
      presentation is a major one as they are more likely to suffer from co-morbidities
      such as diabetes and hypertension.

PMID- 19403247
TI  - A glass fragment for a dagger--never mind your own hand.
AB  - A case of homicide is reported where a woman was killed by her boyfriend. He used
      a dagger-like fragment of a broken window glass to cause 10 atypical stab wounds
      to the neck and face and several incised wounds in other body regions. The cause
      of death was exsanguination, mainly from a severed internal jugular vein. The
      morphology of glass fragment injuries, both in the victim and perpetrator, is
      discussed and the possibility of homicide in such cases, which commonly represent
      accidents, is stressed. The use of an unsuited sharp force weapon carrying a high
      potential for self-injury can be explained by an excited state of mind.

PMID- 19403248
TI  - Scavenging activity can produce predictable patterns in surface skeletal remains
      scattering: observations and comments from two experiments.
AB  - In forensic contexts, surface deposited remains are frequently found that have
      been scattered by various taphonomic processes. In an effort to develop
      strategies to improve recovery rates, this study evaluates whether patterns can
      be detected in the scattering of remains due to scavenger activity. In two
      experiments, 24 human analogues (pig carcasses) were placed in two adjacent but
      differing environmental contexts: 12 in wooded and 12 in open grassland. Six
      carcasses in each of these contexts were dressed in human clothing. Elapsed time
      and direction of movement information for each carcass and its parts were
      collected and analyzed. Unclothed carcasses and carcasses in open contexts
      exhibited scavenger activity sooner than the others. Scattering of remains
      occurred along game trails and was directed away from human population and
      activity. Due to the highly variable nature of scavenger activity, daily
      observations during a research project are the key leading to a better
      understanding of the development of these patterns.

PMID- 19403249
TI  - Finnish sexual homicides: offence and offender characteristics.
AB  - Information on sexual homicide offenders is limited. The current study estimates
      the rate of sexual homicides in Finland and analyses sociodemographic
      characteristics, crime history, life course development, psychopathy, and
      psychopathology in sexual homicide and nonsexual homicide offenders. Crime
      reports and forensic examination reports of all offenders subjected to forensic
      examination and convicted for homicide in 1995-2004 (n=676) were retrospectively
      analyzed for offence and offender variables and scored with the Psychopathy
      Checklist-Revised. Eighteen sexual homicides (2.8%) were identified. Co
      offending, strangulation and disposal of the body were more frequent crime scene
      variables in sexual than nonsexual homicides. Mental health problems and sexual
      abuse in childhood and sexual crime history were significantly more frequent in
      sexual than nonsexual homicide offenders. Over half of the sexual homicide
      offenders were psychopathic: compared to nonsexual homicide offenders they scored
      significantly higher on interpersonal and affective features of psychopathy.

PMID- 19403250
TI  - Bilateral pallidal stimulation in children and adolescents with primary
      generalized dystonia--report of six patients and literature-based analysis of
      predictive outcomes variables.
AB  - INTRODUCTION: Primary generalized dystonia is a rare movement disorder. Medical
      treatment rarely relieves symptoms. The aim of this study was to investigate the
      efficacy and safety of bilateral pallidal stimulation in 6 children and
      adolescents with primary generalized dystonia. In addition, we strived to find
      predictors for treatment outcome by review and analysis of previously published
      studies. METHODS: Six patients with primary generalized dystonia underwent
      chronic bilateral stimulation of the globus pallidus internus. A PubMed and
      MEDLINE search was performed in order to identify children and adolescents who
      underwent deep brain stimulation for primary generalized dystonia. The primary
      efficacy endpoint was the relative change of the Burke-Fahn-Marsden-Dystonia
      Rating-Scale (movement score) after surgery. RESULTS: Forty-four patients were
      found to meet the inclusion criteria. The mean age at onset of the disease was
      7.8+/-2.8years and the mean age at surgery was 14.2+/-3.5years. The mean Burke
      Fahn-Marsden-Dystonia-Rating-Scale (movement score) was 56.9+/-22.7 before
      surgery and 23.7+/-23.2 at a mean follow up of 13.0+/-4.8months (p<0.001). The
      improvement in the DYT1-positive group was significantly higher compared to the
      DYT1-negative group (77%+/-24% and 44%+/-30%, respectively, p<0.001). A positive
      correlation between the movement score before and after surgery was found in both
      the DYT1-positive and DYT1-negative cohort (rs=0.624, p<0.001 and rs=0.734,
      p<0.001, respectively). CONCLUSION: DBS is an effective treatment in children and
      adolescents with primary generalized dystonia. Predictive factors for a better
      treatment outcome are DYT1-positive status and minor motor impairment before
      surgery.

PMID- 19403251
TI  - [Impact of the estimation of the medically insured population on the
      pharmacological prevalence of diabetes at the regional and small area level].
AB  - BACKGROUND: Data derived from Health Insurance databases are very useful for
      health observation. These data are however still underused, particularly for
      small local areas. This may be partly explained by the lack of reliable data on
      the number of insured people. Recent simplification of the Repertoire national
      interregimes de l'assurance-maladie (RNIAM) indicator (French register of health
      insurance) gives the opportunity to improve the usefulness of these databases.
      This indicator specifies the beneficiaries' status towards the General Health
      Insurance Fund. This study aimed to select the population of beneficiaries, which
      could be most adequately used to calculate health indicators based on these data.
      METHODS: Data were collected from the outpatient database of the Southeastern
      France General Health Fund. We compared beneficiaries' characteristics according
      to the RNIAM indicator, calculated the annual unadjusted and age-adjusted
      regional and local prevalence of diabetes mellitus in two different populations:
      the whole initial beneficiaries database, and the population of "effective"
      beneficiaries (persons whose reimbursements were effectively managed by the
      General Health Insurance). RESULTS: The initial database included 4,817,871
      beneficiaries. Almost 80% were in the "effective" population, 14% had left the
      General Health Insurance, or Southeastern France, and 4% were doubles. The annual
      unadjusted prevalence of diabetes mellitus was 3.31% in the initial database, and
      more than 20% higher when calculated among "effective" beneficiaries. Impact on
      aged-adjusted prevalence was less important (+9% at regional level), but the
      increase varied from 6 to 42% for the small local areas. Impact was much higher
      on age and gender specific rates. CONCLUSION: When Health Insurance databases are
      used to calculate health indicators at various geographical levels, only
      "effective" beneficiaries should be selected. The methodology for determining
      health indicators might be improved by updating databases (e.g. the date of the
      RNIAM indicator last update should be added).

PMID- 19403252
TI  - [Degree of emergency for antibiotherapy in patients with presumed bacterial
      meningitis: experimental and clinical data].
AB  - No prospective randomized clinical studies are available to determine exactly how
      much time should be spent on investigation before initiating antibiotherapy in a
      patient with presumed bacterial meningitis. Experimental models show that
      antibiotics should be administered before the inflammatory response, but at this
      time the patient's symptoms are often unspecific. Models also demonstrate that a
      gain of time is beneficial at any time, in terms of inflammation, magnitude of
      bacteremia, or loss of hearing. Very few clinical studies address the acceptable
      delay between admission and administration of antibiotics and two of these show a
      correlation with outcome in adult meningitis. The available data supports the
      recommendation that hospital investigation of a patient with presumed bacterial
      meningitis should be conducted in such a way that efficient antimicrobial
      chemotherapy will be initiated within one hour after arrival.

PMID- 19403253
TI  - [Hereditary hemorragic telangiectasia and hepatic abcess].
AB  - We report the case of a 27-year-old man presenting with a hepatic abscess and
      hereditary hemorrhagic telangiectasia (HHT). The association between HHT and an
      infectious disease seemed to be induced by arteriovenous malformations and maybe
      also by a deficit of polymorphonuclear cells, a monocyte oxidative burst and
      phagocytosis. This diagnosis should be suggested in case of serious infections in
      young patients. Prevention is based on screening for and destroying infection,
      antibioprophylaxis and embolization of arteriovenous malformations.

PMID- 19403254
TI  - [Usefulness of C-reactive protein in the therapeutic follow-up of infected
      patients].
AB  - Monitoring of body temperature, but also of C-reactive protein (CRP) level is
      performed in infected patients treated with antibiotics. These two parameters
      having low specificity for any diagnosis, our aim was to evaluate the usefulness
      of CRP in this context. PATIENTS AND METHOD: A representative sample of patients
      was randomly extracted from our medical computerized tables. All patients
      presented community-acquired infections and had at least two CRP level
      assessments. Kinetics of body temperature and CRP allowed to quantify clinical
      and biological discrepancy while the patient's chart was studied to determine the
      etiologies. RESULTS: Three hundred and ninety-two patients over 942 (42%) were
      admitted in our department over 2 years, including 147 cases of respiratory
      infections (37%), 91 of urinary infections (23%), 65 of cellulitis (17%), 70 of
      primary bacteremia (18%), 19 of digestive infections (5%). Ninety-four percent of
      the patients had been prescribed antibiotic therapy. We observed a correlation
      between temperature and CRP in 83% of the patients. Forty-seven percent of
      patients presented with normalized body temperature and persistently high levels
      of CRP, which was most of the time related to comorbid conditions. Twenty
      patients (5%) presented with unexplained persistent fever despite CRP
      normalization. Therapeutic modifications were mostly observed in the presence of
      clinicobiological discrepancy: 21% versus 6%, p<0.001. DISCUSSION: Body
      temperature and CRP are two parameters leading to comparable information in more
      than 80% of infected patients receiving specific antibiotic therapy. These
      clinical and biological discrepancies are associated to a modified antibiotherapy
      with inconclusive results.

PMID- 19403255
TI  - Whole-body diffusion-weighted magnetic resonance imaging.
AB  - Diffusion-weighted magnetic resonance imaging (DWI) provides information on the
      diffusivity of water molecules in the human body. Technological advances and the
      development of the concept of diffusion-weighted whole-body imaging with
      background body signal suppression (DWIBS) have opened the path for routine
      clinical whole-body DWI. Whole-body DWI allows detection and characterization of
      both oncological and non-oncological lesions throughout the entire body. This
      article reviews the basic principles of DWI and the development of whole-body
      DWI, illustrates its potential clinical applications, and discusses its
      limitations and challenges.

PMID- 19403256
TI  - MRI evaluation of a new scaffold-based allogenic chondrocyte implantation for
      cartilage repair.
AB  - AIM: The present study was designed to evaluate the implantation of alginate
      beads containing human mature allogenic chondrocytes for the treatment of
      symptomatic cartilage defects of the knee. MRI was used for the morphological
      analysis of cartilage repair. The correlation between MRI findings and clinical
      outcome was also studied. METHODS: A biodegradable, alginate-based biocompatible
      scaffold containing human mature allogenic chondrocytes was used for the
      treatment of symptomatic chondral and osteochondral lesions in the knee. Twenty
      one patients were prospectively evaluated with use of the Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analogue Scale
      (VAS) for pain preoperatively and at 3, 6, 9 and 12 months of follow-up. Of the
      21 patients, 12 had consented to follow the postoperative MRI evaluation
      protocol. MRI data were analyzed based on the original MOCART (Magnetic Resonance
      Observation of Cartilage Repair Tissue) and modified MOCART scoring system. The
      correlation between the clinical outcome and MRI findings was evaluated. RESULTS:
      A statistically significant clinical improvement became apparent after 6 months
      and patients continued to improve during the 12 months of follow-up. One of the
      two MRI scoring systems that were used, showed a statistically significant
      deterioration of the repair tissue at 1 year of follow-up. Twelve months after
      the operation complete filling or hypertrophy was found in 41.6%. Bone-marrow
      edema and effusion were seen in 41.7% and 25% of the study patients,
      respectively. We did not find a consistent correlation between the MRI criteria
      and the clinical results. DISCUSSION: The present study confirmed the primary
      role of MRI in the evaluation of cartilage repair. Two MOCART-based scoring
      systems were used in a longitudinal fashion and allowed a practical and
      morphological evaluation of the repair tissue. However, the correlation between
      clinical outcome and MRI findings was poor. Further validation of these scoring
      systems is mandatory. The promising short-term clinical outcome of the allogenic
      chondrocytes/alginate beads implantation was not confirmed by the short-term MRI
      findings.

PMID- 19403257
TI  - The bacterial diversity in an anaerobic ammonium-oxidizing (anammox) reactor
      community.
AB  - An anaerobic ammonium-oxidation (anammox) reactor was operated for more than 500
      days and the anammox activity of the biomass in the reactor reached 0.58 kg
      N(total)/kg VSS d. The removal ratios of NO2(-)-N to NH4(+)-N in both reactor and
      activity tests were nearly 1.1. The bacterial diversity in the reactor was
      investigated by analysis of 16S rRNA gene clone libraries and quantitative real
      time PCR (qPCR). The analysis showed that more than half of the clones in the
      library were affiliated to recognized filamentous bacteria. The previously
      recognized anammox bacterium (AnAOB) Candidatus Kuenenia stuttgartiensis was only
      detected by using a Planctomycetes-specific 16S rRNA gene primer set. However, at
      least two different types of AnAOB were detected by the primer set targeting the
      hydrazine-oxidizing enzyme gene (hzo). The aerobic ammonium-oxidizing bacteria
      (AAOB) Nitrosomonas europaea-eutropha group, which is widely detected in oxygen
      limited environments, was also found in this reactor. The result of qPCR
      indicated that AnAOB comprised 16% of the community population while AAOB
      comprised less than 1% in the reactor.

PMID- 19403258
TI  - Training physicians in shared decision-making-who can be reached and what is
      achieved?
AB  - OBJECTIVE: To report on experiences with a general shared decision-making (SDM)
      physician training program offered to physicians throughout Germany. METHODS:
      This study enrolled 150 physicians in an 8-h SDM training program. Physicians
      were assessed with standardized instruments before and after training. Main
      variables of interest were physician professional attributes, personality
      characteristics, attitudes, measures of training success (quality rating,
      knowledge, competency ratings), and variables associated with training success.
      RESULTS: The SDM training obtained positive quality ratings, led to an
      amelioration in an objective SDM knowledge test (p<.001), and highly improved
      physicians' confidence in their SDM competencies (p<0.001). It attracted
      experienced, middle-aged (45 years), male and female (46%) physicians, mostly
      office-based (2/3) general practitioners and internists (2/3). Most physicians
      (94%) reported positive attitudes towards SDM. They were securely attached (63%)
      with predominant social career choice motives (46%). Physicians with personality
      characteristics clashing with the SDM concept benefited mostly from the training.
      CONCLUSION: A voluntary SDM training program is attractive to practicing
      physicians and effective in increasing SDM-related confidence and knowledge.
      PRACTICE IMPLICATIONS: Even physicians who are highly motivated to use SDM can
      improve their skills and benefit from SDM training. The dissemination of SDM
      training programs should be encouraged.

PMID- 19403259
TI  - Health literacy and physical and psychological wellbeing in Japanese adults.
AB  - OBJECTIVE: To determine the prevalence of low health literacy and investigate the
      relationship between low health literacy and physical and psychological wellbeing
      in the Japanese general population. METHODS: A web-based cross-sectional survey
      was conducted in a national sample of Japanese adults. Health literacy was
      measured by self-report using the validated single-item screening question, "How
      confident are you filling out forms by yourself?" Wellbeing was measured with the
      physical and psychological domains of the World Health Organization Quality of
      Life Assessment-BREF. Effect sizes were computed by dividing the mean difference
      in scores by the standard deviation of the scores of all participants. RESULTS:
      In 1040 adult enrollees (mean age, 57-year-old; women, 52%), there were 161
      (15.5%; 95% confidence interval [CI], 13.3-17.7%) with low health literacy.
      Individuals with low health literacy reported lower physical wellbeing (60.6 vs.
      71.7, p<0.001) and psychological wellbeing (59.7 vs. 68.3, p<0.001) compared with
      those with adequate health literacy. After adjusting for sociodemographic
      characteristics, health risk behaviors and chronic conditions, these differences
      were still significant (physical wellbeing, p<0.001; psychological wellbeing,
      p<0.001). The effect sizes of the difference of scores were moderate for physical
      wellbeing (-0.55) and also for psychological wellbeing (-0.44). CONCLUSION: The
      prevalence of self-reported low health literacy in Japanese adults is substantial
      and it is independently associated with poorer physical and mental wellbeing.
      PRACTICE IMPLICATIONS: Efforts to monitor health literacy and to evaluate causal
      pathways to poor wellbeing should be encouraged in the Japanese population.

PMID- 19403260
TI  - [Difficulty of regional anaesthesia catheter withdrawing due to a knot: three
      case reports].
AB  - We observed three cases of knots after peripheral nerve catheterism. Catheter
      removal was impossible and required the intervention of an anaesthetist. This
      complication should be known and included in the training of nurses. The
      analgesic technique by peripheral nerve catheter is currently used for the
      treatment of acute postoperative pain and starts to be used for the treatment of
      chronic pain. The catheter removal should be included in a protocol. One solution
      might be the use of a network to meet all the complications that happen in
      continuous peripheral nerve blocks, particularly at home.

PMID- 19403261
TI  - [Glycemic control in practical glycemia monitoring].

PMID- 19403263
TI  - Exploiting co-adaptation for the design of symbiotic neuroprosthetic assistants.
AB  - The success of brain-machine interfaces (BMI) is enabled by the remarkable
      ability of the brain to incorporate the artificial neuroprosthetic 'tool' into
      its own cognitive space and use it as an extension of the user's body. Unlike
      other tools, neuroprosthetics create a shared space that seamlessly spans the
      user's internal goal representation of the world and the external physical
      environment enabling a much deeper human-tool symbiosis. A key factor in the
      transformation of 'simple tools' into 'intelligent tools' is the concept of co
      adaptation where the tool becomes functionally involved in the extraction and
      definition of the user's goals. Recent advancements in the neuroscience and
      engineering of neuroprosthetics are providing a blueprint for how new co-adaptive
      designs based on reinforcement learning change the nature of a user's ability to
      accomplish tasks that were not possible using conventional methodologies. By
      designing adaptive controls and artificial intelligence into the neural
      interface, tools can become active assistants in goal-directed behavior and
      further enhance human performance in particular for the disabled population. This
      paper presents recent advances in computational and neural systems supporting the
      development of symbiotic neuroprosthetic assistants.

PMID- 19403262
TI  - The performance of mouse pointing and selecting for pupils with and without
      intellectual disabilities.
AB  - The purpose of this study was to compare the performance of mouse pointing and
      selecting in the tasks with different index of difficulty between 20 pupils with
      intellectual disabilities and 21 pupils without disabilities. A mouse proficiency
      assessment software was utilized to collect data. Pupils with intellectual
      disabilities executed tasks more correctly in bigger target even in tasks with
      the same index of difficulty. The group with intellectual disabilities performed
      worse in cursor control even when only those correctly completed tasks were used
      for comparison. However, a similar pattern was observed in the performance of the
      group without disabilities.

PMID- 19403264
TI  - Agreement between self-reported and health insurance claims on utilization of
      health care: A population study.
AB  - OBJECTIVE: To investigate the agreement between self-reported and insurance claim
      of the utilization of health care. STUDY DESIGN AND SETTING: Data were from the
      Taiwan National Health Interview Survey, conducted in 2001. There were 22,121
      (94.2%) individuals who completed the interview, 18,143 of them aged 12 and
      above. Among them, 87% signed a consent form to allow us linking their interview
      with data with the National Health Insurance database. After deleting those with
      illegible identification code or date of birth, 15,660 subjects were included in
      the study. Kappa (kappa) was used to describe the visit concordance, whereas the
      intraclass correlation coefficient was used to describe frequency consistency.
      Logistic regression was used to investigate factors associated with the
      agreement. RESULTS: All had reasonable visit and frequency agreements. Logistic
      regression showed that males and those living in rural areas tended to have a
      lower likelihood of agreement in reporting outpatient visits compared with
      others. In reporting emergency room visits, males and those with a higher
      education level, self-perceived health of "not good," chronic disease, or at
      least one difficulty with activities of daily living (ADL) had higher chances of
      agreement. CONCLUSION: Agreement between self-reported utilization and insurance
      claims were fairly good in general population.

PMID- 19403265
TI  - Local estimates of population attributable risk.
AB  - OBJECTIVE: To investigate properties of population attributable risk (PAR)
      estimates, when its components come from different sources. Examples include
      situations where one requires local estimates of PAR for a study subset (e.g., in
      states or counties within a national study) or if one wishes to apply the
      findings of an epidemiologic study to another population. STUDY DESIGN AND
      SETTING: A framework for estimating local PAR values is developed, and then
      illustrated using synthetic and empirical data. RESULTS: A general expression for
      the variance of a local PAR estimate is formulated. It involves three components,
      reflecting (1) the variance of the disease relative risk associated with exposure
      to a risk factor, (2) the variance of the exposure prevalence (P), and (3) their
      covariance. The effects of variable stratum sizes, case-control sample size
      ratios, and variation in exposure P are illustrated by some synthetic scenarios,
      and with data from an international case-control study of heart disease.
      CONCLUSION: The precision of local PAR estimates can be considerably improved by
      incorporating external data, as opposed to limiting the calculation to data only
      from the local population. In some cases, variation in local PAR estimates
      largely reflects uncertainty in the local estimate of exposure P.

PMID- 19403266
TI  - Beneficial effects of a low-protein diet on host resistance to Paracoccidioides
      brasiliensis in mice.
AB  - OBJECTIVE: Although protein malnutrition impairs immune functions, several
      studies have recently shown that protein restriction without malnutrition is
      beneficial to host defenses against invading pathogens and cancer. In an effort
      to establish the optimum diet for host resistance, we investigated the effect of
      different dietary protein levels on host resistance to Paracoccidioides
      brasiliensis. METHODS: Mice were fasted for 2 days and then infected with P.
      brasiliensis. Immediately after challenge with this fungus, mice were refed on
      diets with three different levels (0%, 1.5%, or 20%) of casein. On days 0-7 after
      infection, antifungal activity and levels of proinflammatory mediators in the
      spleen and liver were measured. RESULTS: Mice refed on the 1.5% casein diet
      showed higher antifungal activity in the spleen and liver compared with mice on
      the 20% casein diet. The antifungal activity in the spleens of mice refed on the
      0% casein diet was intermediate between the antifungal activities of those refed
      the 1.5% and 20% casein diets. After infection, increases in spleen and liver
      levels of interleukin-6 and interferon-gamma, liver mRNA levels of antimicrobial
      proteins (myeloperoxidase, cathepsin-G, and elastase-2), and liver mRNA levels of
      proinflammatory mediators (interleukin-18, chemokine C-X-C motif ligand 10,
      nuclear factor-kappaB, inducible nitric oxide synthase, and granulocyte
      macrophage colony-stimulating factor) were less profound in mice on the 1.5% or
      0% casein diet compared with mice refed the 20% casein diet. CONCLUSION: The
      present results suggest that protein restriction without malnutrition could be
      beneficial to host resistance to P. brasiliensis.

PMID- 19403267
TI  - Dietary fiber and associations with adiposity and fasting insulin among college
      students with plausible dietary reports.
AB  - OBJECTIVE: We examined dietary fiber intake, food sources of dietary fiber, and
      relation of dietary fiber to body composition and metabolic parameters in college
      students with plausible dietary reports. METHODS: Students (18-24 y of age)
      provided data on anthropometry, fasting blood chemistries, and body composition
      (bioelectric impedance). Diet and physical activity were assessed with the Diet
      History Questionnaire and the International Physical Activity Questionnaire.
      Plausible dietary reporters were identified (+/-1 SD cutoffs for reported energy
      intake as a percentage of predicted energy requirement). Multiple regression
      analyses were conducted with the total (n = 298) and plausible (n = 123) samples,
      adjusting for age, race, sex, smoking status, physical activity, energy intake,
      and fat-free mass (where applicable). RESULTS: Food sources of dietary fiber were
      similar in men and women. In the plausible sample compared with the total sample,
      dietary fiber was more strongly associated with fat mass (beta = -0.24, P <
      0.001), percentage of body fat (beta = -0.23, P < 0.001), body mass index (beta =
      -0.11, P < 0.01), waist circumference (beta = -0.67, P < 0.05), and fasting
      insulin (beta = -0.15, P < 0.001). When the effect of sex was investigated,
      dietary fiber was inversely related to fasting insulin and fat mass in men and
      women and inversely related to percentage of body fat, body mass index, and waist
      circumference in men only (P < 0.05). CONCLUSION: Inclusion of implausible
      dietary reports may result in spurious or weakened diet-health associations.
      Dietary fiber is negatively associated with fasting insulin levels in men and
      women and consistently associated with adiposity measurements in men.

PMID- 19403268
TI  - Senescence mediated redox imbalance in cardiac tissue: Antioxidant rejuvenating
      potential of green tea extract.
AB  - OBJECTIVE: The activities and capacities of antioxidant systems of tissue cells
      are declined during aging, leading to the gradual loss of pro-oxidant/antioxidant
      balance and accumulation of oxidative damage. Hence, the present study evaluated
      the role of green tea extract (GTE), rich in polyphenols, in combating age
      associated macromolecular damage in rat cardiac tissue. METHODS: The antioxidant
      defense system, lipid peroxidation, protein oxidation, and redox status in heart
      tissue were studied using young and aged rats. RESULTS: Significant increases in
      lipid peroxidation, protein carbonyls, and marked decreases in glutathione redox
      status, protein thiols, and activities of enzymatic and non-enzymatic
      antioxidants were observed in aged rats compared with young rats. Supplementation
      of GTE (100 mg/kg of body weight per day) orally for 30 days ameliorated these
      changes significantly. CONCLUSION: This study accredits GTE's antioxidant
      rejuvenating potency and its role in the amelioration of senescence-mediated
      redox imbalance in aged rat cardiac tissue.

PMID- 19403269
TI  - High frequency oscillations and seizure frequency in patients with focal
      epilepsy.
AB  - High frequency oscillations (HFOs) have been associated with epileptogenicity. In
      rats, the extent of HFOs (>200 Hz) is correlated with seizure frequency. We
      studied whether the same applies to patients with focal epilepsy. Thirty-nine
      patients with intracerebral EEG sampled at 2000 Hz were studied for interictal
      ripples (80-250 Hz), fast ripples (FR, 250-500 Hz) and spikes. Seizure frequency
      before implantation was compared to numbers of channels with HFOs (>1/min).
      Analyses were repeated for HFO rates of >5, >10 and >20. Separate analyses were
      done for 25 patients with temporal lobe epilepsy only and for a selection of
      similar unilateral temporal channels in 12 patients. No linear correlation or
      trend was found relating the number of channels with HFOs and seizure frequency.
      There was a linear positive correlation between the number of channels with more
      than 20 FRs/min and seizure frequency. The hypothesis that the more tissue
      generating HFOs, the higher the seizure frequency, was not confirmed, though
      there might be a correlation for high FR rates.

PMID- 19403270
TI  - Cognitive behaviour therapy for improving social recovery in psychosis: cost
      effectiveness analysis.
AB  - A randomised trial was conducted in order to estimate the clinical and cost
      effectiveness of social recovery orientated cognitive behavioural therapy (SRCBT)
      for people diagnosed with psychosis, compared to case management alone (CMA). The
      mean incremental health and social care cost, and the mean incremental quality
      adjusted life year (QALY) gain, of SRCBT was calculated over the 9 month
      intervention period. The cost-effectiveness of SCRBT was in turn estimated, and
      considered in relation to the cost-effectiveness threshold of 20000 UK pounds per
      QALY. The level of uncertainty associated with that decision was estimated by
      calculating the cost-effectiveness acceptability curve for SRCBT. N=35 received
      SRCBT and N=42 received CMA. The mean incremental cost was estimated to be 668 UK
      pounds, and the mean incremental QALY gain 0.035. SRCBT was estimated to be cost
      effective as it had a cost per QALY of 18844 UK pounds, which was more favourable
      than the assumed cost-effectiveness threshold of 20000 UK pounds per QALY. At
      that threshold the probability of being cost-effective was however estimated to
      be 54.3% according to the CEAC, suggesting that further research may be warranted
      in order to reduce the level of uncertainty associated with the decision as to
      whether SRCBT is cost-effective.

PMID- 19403271
TI  - Localization of NAAG-related gene expression deficits to the anterior hippocampus
      in schizophrenia.
AB  - N-acetyl aspartyl glutamate (NAAG) is an endogenous agonist at the metabotropic
      glutamate receptor 3 (mGluR3,GRM3) receptor and antagonist at the N-methyl d
      aspartate (NMDA) receptor, both receptors important to the pathophysiology of
      schizophrenia. Glutamate carboxypeptidase II (GCPII), an enzyme that metabolizes
      NAAG, is also implicated in this illness. In this study, we conducted in situ
      hybridization experiments to examine expression of mGluR3 and GCPII transcripts
      along the rostrocaudal axis of the human postmortem hippocampus. We hypothesized
      that we would find changes in mGluR3 and/or GCPII in the AH but not posterior
      hippocampus (PH) in schizophrenia. We compared mRNA levels of these genes in the
      dentate gyrus (DG) and cornu ammonis (CA)1 and CA3 of AH and PH in 20 matched
      pairs of control and schizophrenia cases. In controls, mGluR3 is highly expressed
      in the DG and at lower levels in CA1 and CA3 while GCP II is expressed at similar
      levels in these regions. Group comparisons show a significant reduction of GCPII
      mRNA level in the AH in schizophrenia. Post hoc analyses reveal this difference
      is localized to the CA1 region. In addition, we find a significant positive
      correlation between GCPII and mGluR3 mRNA in the CA3 of the control AH (r=0.66,
      p=0.008) which is not present in schizophrenia (r=0.096, p=0.76). This may
      reflect a disrupted functional interaction between NAAG and mGluR3 in CA3 in
      schizophrenia. These data suggest that NAAG-mediated signaling is disrupted in
      the AH in schizophrenia and localize the defect to the CA1 and CA3 regions.

PMID- 19403272
TI  - Higher density of label-retaining cells in gingival epithelium.

PMID- 19403273
TI  - Fosfomycin for the treatment of infections caused by multidrug-resistant non
      fermenting Gram-negative bacilli: a systematic review of microbiological, animal
      and clinical studies.
AB  - The treatment of multidrug-resistant (MDR), extensively drug-resistant or pandrug
      resistant non-fermenting Gram-negative bacterial infections constitutes a
      challenge in an era of few new antibiotic choices. This mandates the re
      evaluation of already existing antibiotics such as fosfomycin. We systematically
      reviewed the literature to assess the clinical and microbiological effectiveness
      of fosfomycin in the treatment of these infections by searching PubMed, Scopus
      and the Cochrane Library databases. In 23 microbiological studies identified,
      1859 MDR non-fermenting Gram-negative bacterial isolates were examined. The
      susceptibility rate to fosfomycin of MDR Pseudomonas aeruginosa isolates was
      >or=90% and 50-90% in 7/19 and 4/19 relevant studies, respectively. Cumulatively,
      511/1693 (30.2%) MDR P. aeruginosa isolates were susceptible to fosfomycin.
      Serotype O12 isolates exhibited greater susceptibility. Only 3/85 (3.5%) MDR
      Acinetobacter baumannii and 0/31 MDR Burkholderia spp. isolates were susceptible
      to fosfomycin. Variable criteria of susceptibility were used in the included
      studies. Fosfomycin was synergistic in combination with a beta-lactam,
      aminoglycoside or ciprofloxacin in 46/86 (53.5%) MDR P. aeruginosa isolates. One
      animal study found a good therapeutic effect of the combination
      fosfomycin/gentamicin against MDR P. aeruginosa endocarditis. In six clinical
      studies, 33 patients with MDR P. aeruginosa infections (mainly pulmonary
      exacerbations of cystic fibrosis) received fosfomycin (25/33 in combination with
      other antibiotics); 91% of the patients clinically improved. In conclusion,
      fosfomycin could have a role as a therapeutic option against MDR P. aeruginosa
      infections. Further research is needed to clarify the potential utility of this
      agent.

PMID- 19403275
TI  - Solubilization of poorly water-soluble drug carbamezapine in pluronic micelles:
      effect of molecular characteristics, temperature and added salt on the
      solubilizing capacity.
AB  - The solubilization of a poorly water-soluble antiepileptic drug, carbamazepine
      (CBZ), in a series of micelle-forming PEO-PPO-PEO block copolymers with
      combinations of blocks having different molecular weight was studied. The drug
      solubility and micelle-water partition coefficient (P) were determined using UV
      vis spectroscopy. Dynamic light scattering on copolymer solutions was used to
      measure size and polydispersity of nanoaggregates. Solubilization of
      carbamezapine increased with the rise in temperature and concentration of block
      copolymers, but no significant increase was observed with added salt (NaCl). The
      solubilization is also discussed from a thermodynamics viewpoint, by considering
      the standard free energy of solubilization (DeltaG degrees ).

PMID- 19403274
TI  - Modulation of the Ca2+ conductance of nicotinic acetylcholine receptors by Lypd6.
AB  - The agonist binding sensitivity and desensitization kinetics of nicotinic
      acetylcholine receptors (nAChRs) can be modulated by snake venom neurotoxins and
      related endogenous small proteins of the uPAR-Ly6 family. Here we identify Lypd6,
      a distantly related member of the u-PAR/Ly-6 family expressed in neurons as a
      novel modulator of nAChRs. Lypd6 overexpressed in trigeminal ganglia neurons
      selectively enhanced the Ca2+-component of nicotine-evoked currents through
      nAChRs, as evidenced by comparative whole-cell patch clamp recordings and Ca2+
      imaging in wildtype and transgenic mice overexpressing Lypd6. In contrast, a
      knockdown of Lypd6 expression using siRNAs selectively reduced nicotine-evoked
      Ca2+-currents. Pharmacological experiments revealed that the nAChRs involved in
      this process are heteromers. Transgenic mice displayed behaviors that were
      indicative of an enhanced cholinergic tone, such as a higher locomotor arousal,
      increased prepulse-inhibition and hypoalgesia. These mice overexpressing Lypd6
      mice were also more sensitive to the analgesic effects of nicotine. Transgenic
      mice expressing siRNAs directed against Lypd6 were unable to procreate, thus
      indicating a vital role for this protein. Taken together, Lypd6 seems to
      constitute a novel modulator of nAChRs that affects receptor function by
      selectively increasing Ca2+-influx through this ion channels.

PMID- 19403276
TI  - Interdigitation and vesicle-to-micelle transformation induced by a local
      anesthetic tetracaine in phospholipids bilayers.
AB  - The phase transitions of distearoyl- (DSPC), dipalmitoyl- (DPPC) and dimyristoyl
      phosphatidylcholine (DMPC) bilayer membranes were observed by means of
      differential scanning calorimetry as a function of the concentration of a local
      anesthetic tetracaine hydrochloride (TC.HCl). The depression of both temperatures
      of the main- and pre-transition, which is accompanied by a decrease in enthalpy
      changes for both transitions, was observed initially by the addition of TC.HCl.
      Bilayer interdigitation, which is accompanied by an increase in enthalpy change
      for the main transition from the interdigitated gel phase to the liquid
      crystalline phase, was followed by disappearance of the pretransition. The TC.HCl
      concentration necessary for the bilayer interdigitation was found to be 10, 21
      and 6 mmol kg(-1) for DSPC, DPPC and DMPC bilayers, respectively, which was not
      consistent with the order of acyl-chain length of lipids. Biphasic interactions
      for the interdigitation, that is, repulsive interaction between polar head groups
      and van der Waals attractive interaction between hydrophobic chains of lipids,
      were discussed. On the other hand, vesicle-to-micelle transformation, which is
      accompanied by a cooperative decrease in enthalpy change for the main transition,
      was observed at higher concentration of TC.HCl and was confirmed by the vesicle
      size determined by the dynamic light scattering. The longer the acyl-chain length
      of lipids, the higher the TC.HCl concentration necessary for the vesicle-to
      micelle transformation.

PMID- 19403277
TI  - Effect of polymer viscosity on physicochemical properties and ocular tolerance of
      FB-loaded PLGA nanospheres.
AB  - Poly(lactide-co-glycolide) acid (PLGA) nanospheres incorporating flurbiprofen
      (FB) were produced by the solvent displacement technique, for ocular applications
      aiming to avoid/minimize inflammation induced by surgical trauma. In this work, a
      PLGA of low viscosity has been tested and the results obtained were compared with
      those previously reported by Vega et al. The physicochemical properties of the
      developed formulations were evaluated by measuring particle size, zeta potential
      and FB entrapment efficiency, showing no significant differences. Release studies
      demonstrated that the formulation produced with PLGA of higher viscosity revealed
      a slower drug release rate. Stability analysis, for a period of 75 days, was
      performed using three complementary methods: (i) turbidity experiments using a
      Turbiscan optical analyzer, (ii) particle size measurements, and (iii) zeta
      potential analysis. The results revealed long-term physicochemical stability
      suitability for ophthalmic use, being independent from the polymer viscosity. The
      ocular tolerance was assessed by an alternative in vitro method to animal
      experimentation, the HET-CAM. For all developed formulations no ocular irritancy
      has been detected.

PMID- 19403278
TI  - Double emulsions stabilized by a charged complex of modified pectin and whey
      protein isolate.
AB  - Double emulsions based on naturally occurring stabilizers for food applications
      were studied. Two charged biopolymers, whey protein isolate (WPI) and enzymatic
      modified pectins, interacted in aqueous solution to form a charge-charge complex
      that was utilized as a hydrophilic polymeric steric stabilizer improving the
      double emulsion stability. The main factors that influence the interaction
      between protein and pectin were investigated in relation to double emulsion
      stability: creaming, coalescence, and water transport between aqueous phases. The
      pH determined the size of the complex formed. Thus at pH 6, where a soluble
      complex was obtained between some molecular positively charged patches on the
      protein and negatively charged fractions of the hydrocolloids, the double
      emulsion was the most stable. With the smallest droplet size (ca. 15 microm), the
      lowest creaming, highest yield, and minimized water transport were obtained. The
      best concentration and ratio to form the soluble complex are 4 wt% WPI and 0.5
      wt% pectin (for 30 wt% of the W/O inner phase). The influence of the charge
      distribution (degree of order of the carboxylic groups) of the pectin on the
      associated complex was also investigated, and it was found that the more
      "ordered" pectin (U63) formed the most stable double emulsion against water
      transport.

PMID- 19403279
TI  - Flexible polymerosomes--an alternative vehicle for topical delivery.
AB  - Self-assembled vesicles of poly(caprolactone)-poly(ethylene glycol)
      poly(caprolactone) co-polymer of 122+/-20 nm were prepared by solvent evaporation
      method and analyzed morphologically by TEM and AFM. Transmission electron
      micrographs showed the presence of double-walled deformable structures with
      average wall thickness of 25 nm. AFM depicted somewhat flattened tops resembling
      a 'pancake' further confirming the flexibility of the nanocarriers. Permeation
      studies of fluorescently labelled vesicles in cadaver epidermis confirmed their
      presence across the stratum corneum within 2h of application and accumulation in
      the deeper layers thereafter. The flexible nature of these nanosystems makes them
      an efficient alternative to liposomes for targeting melanomas and basal cell
      carcinomas.

PMID- 19403281
TI  - Entropy and complexity measures for EEG signal classification of schizophrenic
      and control participants.
AB  - OBJECTIVE: In this paper, electroencephalogram (EEG) signals of 20 schizophrenic
      patients and 20 age-matched control participants are analyzed with the objective
      of classifying the two groups. MATERIALS AND METHODS: For each case, 20 channels
      of EEG are recorded. Several features including Shannon entropy, spectral
      entropy, approximate entropy, Lempel-Ziv complexity and Higuchi fractal dimension
      are extracted from EEG signals. Leave-one (participant)-out cross-validation is
      used for reliable estimate of the separability of the two groups. The training
      set is used for training the two classifiers, namely, linear discriminant
      analysis (LDA) and adaptive boosting (Adaboost). Each classifier is assessed
      using the test dataset. RESULTS: A classification accuracy of 86% and 90% is
      obtained by LDA and Adaboost respectively. For further improvement, genetic
      programming is employed to select the best features and remove the redundant
      ones. Applying the two classifiers to the reduced feature set, a classification
      accuracy of 89% and 91% is obtained by LDA and Adaboost respectively. The
      proposed technique is compared and contrasted with a recently reported method and
      it is demonstrated that a considerably enhanced performance is achieved.
      CONCLUSION: This study shows that EEG signals can be a useful tool for
      discrimination of the schizophrenic and control participants. It is suggested
      that this analysis can be a complementary tool to help psychiatrists diagnosing
      schizophrenic patients.

PMID- 19403280
TI  - [Extreme prematurity: comparison of outcome at 5 years depending on gestational
      age below or above 26 weeks].
AB  - OBJECTIVE: Is it reasonable to care for children born under 26 gestational weeks
      (GW)? To answer this question, we compared outcome at 5 years of 2 groups of
      children:less or equal to 25 GW+6 days (group 1) and 26-27 GW+6 days (group 2).
      METHOD: Retrospective study on extremely preterm children hospitalized in our
      center between 1999 and 2001. Perinatal data were obtained from medical reports.
      Five-year outcome was evaluated by questionnaire sent to Centers for Early
      Medicosocial Intervention, pediatricians or the child's parents. The children
      were classified according to their disability: none, minor or major. Progression
      was considered favorable if the child survived with or without minor disability
      and unfavorable if the child had died or had major disability. RESULTS: One
      hundred and sixty-six preterm babies were recorded. In group 1 (n=63), mortality
      was higher (58% vs 29%; p=0.0002), a neurologic cause was often responsible for
      death (36% vs 19%; p=0.018), a high level of intracranial hemorrhage was more
      frequent (35% vs 19%; p=0.002), and a decision to stop healthcare more often made
      (35% vs 18%; p=0.01) than in group 2 (n=103). Among the 99 survivors, 78 were
      being followed up at 5 years of age. In terms of disability, no difference was
      observed between group 1 (n=21) and group 2 (n=57). Including deaths, the risk
      for unfavorable progression was higher in group 1 (64% vs 41%; p=0.008).
      CONCLUSION: The progression of under 26-GW preterm babies is more often
      unfavorable than the progression of babies born 26-27 GW+6 days. However, given
      the low number of patients, no significant difference was made concerning the
      prognosis at 5 years between the survivors of the 2 groups.

PMID- 19403282
TI  - Radiochemotherapy for lung cancer in developing countries.
AB  - Radiochemotherapy has become a standard approach in locally advanced non-small
      cell lung cancer and limited disease small cell lung cancer. Most of the data
      supporting this observation come from the developed world and only extremely
      rarely have good-quality clinical trials been carried out in developing
      countries. It is therefore of paramount importance to put the experience of the
      developed world into the context of the limited resources and other health care
      problems of developing countries. In this overview, the problems with the
      implementation of such data are discussed. The necessity of carrying out clinical
      trials specifically designed to address the needs of developing countries is
      emphasised. The research on cheaper ways of radiochemotherapy combination should
      be encouraged. The specific national guidelines for local needs should be created
      and followed. The availability of radiotherapy equipment is of major importance,
      as radiotherapy has a pivotal role in non-surgical treatment of lung cancer,
      especially in the developing world.

PMID- 19403284
TI  - Experimental models of peripheral neuropathic pain based on traumatic nerve
      injuries - an anatomical perspective.
AB  - Peripheral neuropathic pain (PNP) frequently occurs as a consequence of nerve
      injury and may differ depending upon the type of insult and the individual
      patient. Progress in our knowledge of PNP induction mechanisms depends upon the
      utilization of appropriate experimental models in rodents based on various types
      of peripheral nerve lesions. In this review, we draw attention to current
      knowledge on basic cellular and molecular events in various experimental models
      used to induce the PNP symptoms. Spontaneous ectopic activity of axotomized and
      non-axotomized primary sensory neurons, the bodies of which are located in the
      dorsal root ganglion (DRG), seems to be a key mechanism of PNP induction. The
      primary sensory neurons are directly affected by nerve injury or indirectly by
      activated satellite glial cells and adjoining immune cells that release a variety
      of molecules changing the microenvironment of the neurons. Recently, it has
      become clear that molecules produced during Wallerian degeneration play an
      important role not only in axon-promoting conditions distal to nerve injury but
      also in initiation of neuropathic pain. The molecules, transported by the blood,
      influence afferent neurons and their axons not only in DRG associated, but also
      those not directly associated with the injured nerve (i.e., in the contralateral
      DRG or at different spinal segments). Generally, all experimental PNP models
      based on a partial injury of peripheral nerve segments contain mechanisms
      initiated by signal molecules of Wallerian degeneration.

PMID- 19403283
TI  - APOE, CETP and LPL genes show strong association with lipid levels in Greek
      children.
AB  - BACKGROUND AND AIMS: Studies have consistently demonstrated that variants in a
      number of candidate genes are significant determinants of lipid levels in adults.
      However, few studies have investigated the impact of these variants in children.
      Therefore, in the present investigation we examined the influence of ten common
      variants in the genes for lipoprotein lipase (LPL-S447X), cholesterol ester
      transfer protein (CETP-Taq1B) apolipoprotein (APO) E (epsilon2, epsilon3,
      epsilon4), APOA5 (-1131C>T and S19W), APOA4 (S347T) and APOC3 (-482C>T; 1100C>T
      and 3238G>C) on lipoprotein levels children from the Gene-Diet Attica
      Investigation on childhood obesity (GENDAI). METHODS AND RESULTS: The ten
      variants selected were genotyped in 882 Greek children, mean age: 11.2+/-0.7
      years (418 females and 464 males). Genotypes were assessed using TaqMan
      technology. Significantly higher total cholesterol (TC) (p=0.0001) and low
      density lipoprotein cholesterol (LDL-C) (p<0.0001) were observed in APOE epsilon4
      carriers compared to epsilon3/epsilon3 homozygotes and epsilon2 carriers. The
      association of APOE genotype with TC and high-density lipoprotein cholesterol
      (HDL-C) ratio (p=0.0008) was further modulated by body mass index. Carriers of
      the CETP TaqIB B2 allele had significantly higher HDL-C (p<0.0001) and
      significantly lower TC: HDL-C ratio (p<0.0001) compared to B1/B1 individuals. No
      significant associations were observed between APOA4, APOA5 and APOC3 variants
      and serum lipids. CONCLUSION: This study demonstrates that these common variants
      are associated with lipid levels in this healthy paediatric cohort, suggesting
      that even in these young children there may be potential in predicting their
      lifelong exposure to an adverse lipid profile.

PMID- 19403285
TI  - Antiproliferation and apoptosis of human tumor cell lines by a lectin (AMML) of
      Astragalus mongholicus.
AB  - A lectin (AMML) from the roots of Astragalus mongholicus was extracted and
      purified by affinity chromatographic technique. Human cervical carcinoma cell
      line (HeLa), human osteoblast-like cell line (MG63) and human leukemia cell line
      (K562) were used to check the effects of AMML on cell proliferation, apoptosis
      and cell cycle. Maximum growth inhibition (92%) was observed with HeLa cells,
      followed by K562 cells (84%) and MG63 (48%) cells. Morphological observation
      showed that AMML-treated HeLa cells displayed outstanding apoptosis
      characteristics, such as nuclear fragmentation and appearance of membrane
      enclosed apoptotic bodies. The apoptosis of HeLa cells was confirmed by flow
      cytometry using Annexin V/FITC and propidium iodide (PI) staining technique. For
      the first time we also report a significant cell cycle arrest at S phase of HeLa
      cells by AMML. Therefore, the present investigation may lead to the possible
      therapeutic use of Astragalus mongholicus lectin.

PMID- 19403287
TI  - Berberine increases expression of GATA-2 and GATA-3 during inhibition of
      adipocyte differentiation.
AB  - It is known that a number of transcription factors are key regulators in the
      complex process of adipocyte differentiation including peroxisome proliferator
      activated receptor gamma (PPARgamma) and the CCAAT enhancer binding protein alpha
      (C/EBPalpha). Studies have demonstrated that in pre-adipocyte 3T3-L1 cells
      constitutive expression of the DNA binding proteins GATA-2 and GATA-3 results in
      protein/protein interactions with C/EBPalpha resulting in down regulation of
      PPARgamma and subsequent suppressed adipocyte differentiation with cells trapped
      at the pre-adipocyte stage. Thus it appears that GATA-2 and GATA-3 are of
      critical importance in regulating adipocyte differentiation through molecular
      interactions with PPARgamma and C/EBPalpha. Recent reports suggest that
      berberine, an isoquinoline derivative alkaloid isolated from many medicinal herbs
      prevents differentiation of 3T3-L1 cells via a down regulation of PPARgamma and
      C/EBPalpha expression. The aim of this study was to determine the effect of
      berberine on GATA-2 and 3 gene and protein expression levels during
      differentiation of 3T3-L1 cells. MTT (Methylthiazolyldiphenyl-tetrazolium
      bromide) was used to detect the cytotoxic effects of berberine on the viability
      of 3T3-L1 cells during proliferation and differentiation. Differentiation of 3T3
      L1 cells was monitored by Oil Red O staining and RT-PCR of PPARgamma and
      C/EBPalpha and the expression of GATA-2 and 3 was determined by RT-PCR and
      Western Blot. Results show that following treatment with 8microM berberine the
      mRNA and protein expression levels of GATA-2 and 3 were elevated and accompanied
      by inhibited adipocyte differentiation. These results may lead to the use of
      berberine to target the induction of specific genes such as GATA-2 and GATA-3
      which affect adipocyte differentiation.

PMID- 19403286
TI  - The effects of Rhodiola rosea extract on 5-HT level, cell proliferation and
      quantity of neurons at cerebral hippocampus of depressive rats.
AB  - The purpose of this study was to investigate the effects of Rhodiola rosea
      extract and depression on the serotonin (5-HT) level, cell proliferation and
      quantity of neurons at cerebral hippocampus of depressive rats induced by Chronic
      Mild Stress (CMS). Seventy male Sprague-Dawley rats were divided into seven
      groups (10 per group): normal control group, untreated depressive rat model
      group, negative control group, positive control group, low dosage Rhodiola rosea
      extract (1.5g/kg) group, medium dosage Rhodiola rosea extract (3g/kg) group and
      high dosage Rhodiola rosea extract (6g/kg) group. After the depressive rats
      induced by CMS had received Rhodiola rosea extract for 3 weeks, the 5-HT levels
      at cerebral hippocampus were detected by high performance liquid chromatography.
      Bromodeoxyuridine (BrdU) was injected in vivo to label the proliferating cells at
      hippocampus, and morphometry was used to count the hippocampal neurons. The
      results showed that the 5-HT level of the three experimental groups had recovered
      to normal status. The immunohistochemistry of hippocampus BrdU positive cells had
      returned to the normal level in the group of depressive rats with low dosage
      Rhodiola rosea extract. In conclusion the results demonstrated that Rhodiola
      rosea extract could improve 5-HT level in hippocampus in depressive rats, and low
      dosage Rhodiola rosea could induce neural stem cell proliferation at hippocampus
      to return to normal level, repairing the injured neurons at hippocampus.

PMID- 19403288
TI  - Anti-allergic principles of Rhinacanthus nasutus leaves.
AB  - Three naphthoquinone derivatives, rhinacanthin-C (1), -D (2) and -N (3) were
      isolated from the extract of Rhinacanthus nasutus Kurz leaves and were tested for
      anti-allergic effect. The result indicated that all three compounds possessed
      very potent anti-allergic activity against antigen-induced beta-hexosaminidase
      release as a marker of degranulation in RBL-2H3 cells with IC(50) values of 6.9,
      8.9 and 6.4 microM, respectively. In addition, the effects of rhinacanthin-C, -D
      and -N on antigen-induced release of TNF-alpha and IL-4 were also examined. It
      was found that rhinacanthin-C showed the most potent on antigen-induced TNF-alpha
      release with an IC(50) value of 0.7 microM, followed by rhinacanthin-D
      (IC(50)=3.8 microM) and rhinacanthin-N (IC(50)=10.3 microM), whereas those for IL
      4 were rhinacanthin-D (IC(50)=5.4 microM), rhinacanthin-C (IC(50)=7.0 microM) and
      rhinacanthin-N (IC(50)=12.0 microM), respectively. The mechanisms in the late
      phase reaction of rhinacanthin-C, -D and -N were found to inhibit TNF-alpha and
      IL-4 gene expression in antigen-induced TNF-alpha and IL-4 releases on from RBL
      2H3 cells as dose-dependent manners. The structure-activity trends of
      rhinacanthin-C,-D and-N on the inhibition of TNF-alpha release are as follow;
      substitution with octadienoic acid (rhinacanthin-C) conferred much higher
      activity than that of benzodioxo carboxylic acid ester (rhinacanthin-D) as well
      as naphthalene carboxylic acid ester (rhinacanthin-N). For the inhibition of IL-4
      release, the substitution with octadienoic acid (rhinacanthin-C) and benzodioxo
      carboxylic acid ester (rhinacanthin-D) possessed the effect two-fold higher than
      that of naphthalene carboxylic acid ester (rhinacanthin-N). As regards active
      constituents for anti-allergic activity of R. nasutus, rhinacanthin-C, -D and -N
      are responsible for anti-allergic effect of this plant on both the early phase
      and late phase reactions. The finding may support the traditional use of R.
      nasutus leaves for treatment of allergy and allergy-related diseases.

PMID- 19403289
TI  - Effects of major tanshinones isolated from Danshen (Salvia miltiorrhiza) on rat
      CYP1A2 expression and metabolism of model CYP1A2 probe substrates.
AB  - This study explored the effects of Danshen on metabolism/pharmacokinetics of
      model CYP1A2 substrates and hepatic CYP1A2 expression in rats. The effects of
      Danshen and tanshinones on CYP1A2 activity was determined by metabolism of model
      substrates in vitro (phenacetin) and in vivo (caffeine). HPLC was used to
      determine model substrates/metabolites. The effect of Danshen on CYP1A2
      expression was determined by Western blot. Tanshinones (1.25-50 microM)
      competitively inhibited phenacetin O-deethylation in vitro. Inhibition kinetics
      studies showed the K(i) values were in the order: dihydrotanshinone (3.64
      microM), cryptotanshinone (4.07 microM), tanshinone I (22.6 microM) and
      tanshinone IIA (23.8 microM), furafylline (35.8 microM), a CYP1A2 inhibitor. The
      Ki of Danshen extract (mainly tanshinones) was 72 microg/ml. Acute Danshen
      extract treatment (50-200mg/kg, i.p.) decreased metabolism of caffeine to
      paraxanthine, with overall decrease in caffeine clearance (14-22%); increase in
      AUC (11-25%) and plasma T(1/2) (12-16%). Danshen treatment with (100mg/kg/day,
      i.p. or 200mg/kg/day, p.o.) for three or fourteen days showed similar
      pharmacokinetic changes of the CYP1A2 probe substrate without affecting CYP1A2
      expression. This study demonstrated that major tanshinones competitively
      inhibited the metabolism of model CYP1A2 probe substrates but had no effect on
      rat CYP1A2 expression.

PMID- 19403290
TI  - Effect of Bacopa monniera on liver and kidney toxicity in chronic use of opioids.
AB  - In the present study, we investigated the protective effect of Bacopa monniera,
      an indigenous Ayurvedic medicinal plant in India, against morphine-induced liver
      and kidney toxicity in rats. Morphine intoxicated rats received 10-160 mg/kg body
      weight of morphine hydrochloride intraperitoneally for 21 days. Bacopa monniera
      Extract (BME) pretreated rats were administered with BME (40 mg/kg) orally once a
      day 2 h before the injection of morphine for 21 days. Pretreatment with BME has
      shown to possess a significant protective effect against morphine-induced liver
      and kidney functions in terms of serum glutamate oxaloacetate transaminase, serum
      glutamate pyruvate transaminase, alkaline phosphatase, lactate dehydrogenases and
      gamma-glutamyl transferase activities and urea, creatinine and uric acid level
      respectively. Histopathological changes of liver and kidney were also in
      accordance with the biochemical findings. The results of this study indicate that
      Bacopa monniera extract exerted a protection against morphine-induced liver and
      kidney toxicity.

PMID- 19403291
TI  - Spasmolytic and anti-inflammatory effects of constituents from Hertia
      cheirifolia.
AB  - A sesquiterpenoid Bakkenolide (1), and two steroids, (3beta, 22E)-Stigmasta-5, 22
      diene-3-ol (Stigmasterol) (2) and stigmasterol 3beta-glucoside (3), isolated from
      the Hertia cheirifolia (L.) chloroform extract, were evaluated respectively for
      their spasmolytic and anti-inflammatory activities. We note that these natural
      products were isolated and purified for the first time from the specie Hertia
      cheirifolia. Their structures have been established by spectroscopy (1 and 2D NMR
      experiences) and mass spectrometry. Chloroform-, ethyl acetate- and methanol
      extracts were also tested for their spasmolytic and anti-inflammatory activities.
      Spasmolytic and anti-inflammatory screening were based respectively on the
      contractile response effects on rat isolated smooth muscles and on the dose
      related carrageenan induced paw edema in rats. screening of the crude extracts
      showed spasmolytic and anti-inflammatory positive results. The antispasmodic
      effect of Bakkenolide was found in the same range as that of Alverine, a standard
      musculotropic spasmolytic agent.

PMID- 19403292
TI  - Vasodilatory actions of xanthones isolated from a Tibetan herb, Halenia
      elliptica.
AB  - In this study, six major xanthones, isolated and identified from Halenia
      elliptica were investigated for their vasodilatory actions in isolated rat
      coronary artery. The xanthones, including 1-hydroxy-2,3,5-trimethoxy-xanthone (HM
      1), 1-hydroxy-2,3,4,7-tetramethoxy-xanthone (HM-2), 1-hydroxy-2,3,4,5
      tetramethoxy-xanthone (HM-3), 1,7-dihydroxy-2,3,4,5-tetramethoxy-xanthone (HM-4),
      1,5-dihydroxy-2,3-dimethoxy-xanthone (HM-5) and 1,7-dihydroxy-2,3-dimethoxy
      xanthone (HM-7) caused vasodilation in the coronary artery pre-contracted with 1
      microM 5-hydroxytryptamine (5-HT), with EC(50) values ranging from 1.4+/-0.1
      microM (HM-1) to 6.6+/-1.4 microM (HM-2). The EC(50) values of the other
      xanthones were between those of HM-1 and HM-2. Removal of endothelium of the
      coronary artery led to decreases in the vasorelaxant effects of HM-1, HM-7 but
      not HM-2, HM-3, HM-4 and HM-5. Our results showed that xanthones isolated from
      Halenia elliptica are vasoactive substances which exhibit either endothelium
      dependent or endothelium-independent mechanisms in rat coronary artery. The
      potency and mechanism(s) of the vasorelaxant effects of these xanthones may be
      relevant to the structure-activity differences in the level and the position of
      the substituent groups with the primary xanthone structure.

PMID- 19403293
TI  - Comparative research of chemical constituents, antifungal and antitumor
      properties of ether extracts of Panax ginseng and its endophytic fungus.
AB  - The chemical compositions and bioactivities of ether extracts of an endophytic
      fungus Paecilomyces sp. isolated from Panax ginseng were reported, and the
      comparative analysis of the constituents, antifungal and antitumor properties of
      the ether extracts from this fungus and its host ginseng were also conducted. By
      means of GC/MS technique, 51 compounds of Panax ginseng and 38 compounds of
      Paecilomyce sp. were determined. It is attractive that the extracts derived from
      Paecilomyce sp. and ginseng samples contained the same compound falcarinol, a
      natural pesticide and anti-cancer agent. The ether extracts of Paecilomyce sp.,
      tested at 7.8 microg/ml, completely inhibited the visible growth of Pyricularia
      oryzae. Furthermore, both extracts were tested against four human pathogenic
      fungi and showed the IC(80) of Paecilomyce sp. was 4 microg/ml against
      Trichophyton rubrum, equally to the control. Finally, the in vitro antitumor
      experience showed that the most of the IC(50) values were all being below 20
      microg/ml.

PMID- 19403294
TI  - Antifungal activity of tea tree oil from Melaleuca alternifolia against
      Trichophyton equinum: an in vivo assay.
AB  - Dermatophytes are a group of keratinophilic and keratinolytic molds, some of
      which are responsible for ringworm. Among them Trichophyton equinum, which mostly
      infects equids, can cause extensive outbreaks in stud farms. The conventional
      treatment of equine trichophytosis is topic, based upon medicated shampoos to
      reduce the spread of infection among the animals. Nevertheless the popularity of
      phytotherapy is at an all-time peak, and the interest for natural alternatives or
      complements to conventional drug therapy is challenging both in human and
      veterinary field. Among herbal remedia Tea Tree Oil (TTO) shows a wide range of
      antimicrobial activities. A randomized open clinical trial was carried out on 60
      thoroughbred breeding horses affected by equine ringworm. The animals were
      randomly divided into 2 groups of 30 subjects. Diagnostic criteria were the
      presence of clinical signs and positive T. equinum culture. Specificity control
      using TTO mixture in 5 not dermatophyte affected animals was achieved also. The
      antimycotic activity against T. equinum of a mixture containing 25% TTO in sweet
      almond oil, was evaluated in vivo treating 30 subjects, the others were
      administered enilconazole 2% solution. The animals of both groups were topically
      treated twice a day for 15 days with a 25% mixture of TTO diluted in sweet almond
      oil and every 3 days, four times with enilconazole rinses, respectively. The
      clinical and mycological outcome were evaluated at day 30 from the start of the
      treatments. Data analysis was performed by chi square test. All the treated
      animals showed complete clinical and aetiological healing. Part of control
      subjects also, showed an improvement and none of them exacerbate the lesions.
      This therapeutic protocol appears to be effective and versatile, being applicable
      immediately after physical examination, prior to have the laboratory response. It
      could be an alternative for practitioners interested in herbal medicines,
      contributing to fulfill the gap existing between in vitro and clinical studies.

PMID- 19403295
TI  - Impairment of 8-iso-PGF(2ALPHA) isoprostane metabolism by dietary conjugated
      linoleic acid (CLA).
AB  - 8-iso-PGF(2alpha) isoprostane (IP) is one of the most-used markers of lipid
      peroxidation in experimental models and humans. After its formation, it is
      promptly metabolized to 2,3 dinor (DIN) in peroxisomes. Conjugated linoleic acid
      (CLA) is preferentially beta-oxidized in peroxisomes which may compete with IP,
      and thereby may affect its metabolism. In order to verify whether CLA is able to
      influence IP formation and/or metabolism and to explain the mechanism, we
      challenged rats supplemented with CLA or with triolein (as a control fatty acid),
      with a single dose of carbon tetrachloride (CCl(4)) or of bacterial
      lipopolysaccharide (LPS). The results showed that IP and its precursor
      arachidonic acid hydroperoxide, as well as malondialdehyde (MDA), increase
      significantly in the liver of rats challenged with CCl(4), irrespective of the
      diet, while in LPS-treated rats only nitrites in liver and isoprostane in plasma
      increase. On the other hand, the peroxisomal beta-oxidation products of IP, the
      DIN, is significantly lower in the CLA group with respect to control and triolein
      groups. To further investigate whether this is due to competition between CLA and
      IP at the cellular level, we incubated human fibroblasts from healthy subjects or
      patients with adrenoleukodystrophy (ALD), with CLA and/or commercially available
      IP. The rationale of this approach is based on the deficient peroxisomal beta
      oxidation of fibroblasts from ALD patients, leading to a reduced formation of
      DIN. In both normal and ALD cells, the presence of CLA significantly inhibits the
      formation of DIN from IP. We may conclude that both in vitro and in vivo studies
      strongly suggest that CLA may impair IP catabolism in peroxisomes. Consequently
      an increase of IP, as a sole result of CLA intake, cannot be considered as a
      marker of lipid peroxidation.

PMID- 19403296
TI  - Pulmonary function testing in patients with pulmonary arterial hypertension.
AB  - BACKGROUND: Although previous studies have shown that peripheral airway
      obstruction can occur in idiopathic PAH (IPAH), pulmonary function tests have not
      been well-studied in patients with PAH associated with congenital heart disease
      (CHD-PAH) and connective tissue disease (CTD-PAH). METHODS: A multicenter
      prospective study was performed in PAH patients in China. Pulmonary function
      tests were evaluated in 190 PAH patients. RESULTS: Total lung capacity (TLC),
      residual volume (RV) and total airway resistance (Rtot) were similar in PAH
      patients and controls. However, measures of airflow, including vital capacity
      (VC), forced vital capacity (FVC), forced expiratory volume in 1s (FEV(1)),
      FEV(1)/FVC and MEF(50) were decreased in PAH group. Single-breath diffusion
      capacity for carbon monoxide (DL(CO)) was also decreased in PAH patients.
      Expiratory flow-volume curves showed reduction and a curvilinear appearance in
      patients with PAH. Similar changes were observed among the various subgroups of
      IPAH, CHD-PAH, and CTD-PAH patients. More CTD-PAH patients had abnormal DL(CO).
      CONCLUSIONS: Airway obstruction is common in IPAH, CHD-PAH and CTD-PAH patients.
      CTD-PAH patients have lower DL(CO). Hemodynamics, serum markers and exercise
      capacity parameters did not correlate well with pulmonary function indices.

PMID- 19403297
TI  - Drug policing, harm reduction and health: directions for advocacy.

PMID- 19403298
TI  - An integrated microfluidic system for C-reactive protein measurement.
AB  - This study presents a new microfluidic chip integrated with pneumatic micropumps,
      normally close microvalves and vortex-type micromixers for C-reactive protein
      (CRP) measurement. CRP is a protein produced during the inflammation process. It
      has been reported that CRP in serum can be used for risk assessment of
      cardiovascular diseases. In this study, CRP measurements were performed by using
      the integrated microfluidic chip incorporated with magnetic beads. The magnetic
      beads coated with CRP-specific DNA aptamers were used to recognize, purify and
      enrich the target CRP. The entire process including sample pre-treatment, and the
      interaction between the target CRP and anti-CRP antibody was automatically
      performed on a single chip. The chemiluminescence signal was measured using a
      luminometer to detect the concentration of CRP afterwards. The entire reaction
      time is less then 25 min, which is only about 20% of the time required when
      compared to using traditional bench-top machines (150 min). More importantly, the
      detection limit has been improved from 0.125 to 0.0125 mg/L with only half the
      amount of reagent consumption. The development of this microfluidic system is
      promising for fast, accurate, and sensitive detection of CRP.

PMID- 19403299
TI  - Iridium oxide nanomonitors: clinical diagnostic devices for health monitoring
      systems.
AB  - The objective of this research is to demonstrate the potential of iridium oxide
      (IrOx) nanowires based device towards detection of proteins that are disease
      biomarkers. This device is based on electrical detection of protein biomarkers
      wherein an immunoassay is built onto the iridium oxide nanowires that in turn
      undergoes specific electrical parameter perturbations during each binding event
      associated with the immunoassay. Detection of two inflammatory proteins C
      reactive protein (CRP) and Myeloperoxidase (MPO) that are biomarkers of
      cardiovascular diseases is demonstrated. The performance metrics of the device in
      response to the two biomarkers in pure form and in serum samples were evaluated
      and compared to standard ELISA assays. The methodology that has been adopted is
      based on measuring impedance and calibrating its change in magnitude with
      concentration of proteins. We demonstrate the following performance metrics:
      limits of detection up to 1 ng/ml for CRP and 500 pg/ml for MPO in pure and serum
      samples; linear dynamic range of detection from 10 ng/ml to 100 microg/ml for CRP
      and 1 ng/ml to 1 microg/ml for MPO and cross-reactivity contained at less than
      10% of selective binding for both the inflammatory proteins. Iridium oxide has an
      ability to detect very small changes to the surface charge and this capability is
      utilized for achieving the performance metrics and forms the basis of the key
      innovations of this technology, which are, improving the selectivity and
      sensitivity of detection.

PMID- 19403300
TI  - CD133 and nuclear beta-catenin: the marker combination to detect high risk cases
      of low stage colorectal cancer.
AB  - Nuclear beta-catenin and CD133 are linked with two hallmarks of colon cancer,
      wingless-type mouse mammary tumour virus integration site (WNT)-pathway
      dysregulation and colon cancer stem cells (Co-CSCs), respectively. Both molecules
      may be related, as Co-CSCs were proposed to require activated WNT-signalling and
      as CD133 was postulated as a WNT/beta-catenin target gene. Herein, we
      investigated the expression of these markers on serial sections of 162 stage IIA
      colonic adenocarcinomas. We found that the expression of these molecules is
      statistically independent and that they mark distinct but overlapping
      subpopulations of the tumour cells. Moreover, we show that their combined
      evaluation can identify colon cancer cases with vastly reduced survival (hazard
      ratio (HR) 13.4, 95% confidence interval (CI): 4.7-38.2) and a high risk of
      tumour progression (HR 6.8, 95%CI: 3.1-15.0). In conclusion, the independence of
      these markers may on the one hand have implications for their presumed value to
      identify Co-CSCs; on the other hand it allows their combined analysis to become a
      powerful tool to identify high risk cases of stage IIA colon cancer.

PMID- 19403301
TI  - FASLG polymorphism is associated with cancer risk.
AB  - Many studies have reported the association between the FASLG -844T/C polymorphism
      and cancer risk, but the data are remaining controversial. A pooled analysis was
      performed to assess this relationship comprehensively. Medline, PubMed, Embase
      and Web of Science were searched, and data were extracted and cross-checked
      independently by three authors. A total of 18 published studies including 22389
      subjects were involved in this analysis. Overall, the -844C allele was associated
      with a significantly increased cancer risk (for CC versus TT: OR=1.23, 95%
      confidence interval (CI)=1.04-1.45; for CC+TC versus TT: OR=1.15, 95% CI=1.01
      1.30; for CC versus TT+TC: OR=1.20, 95% CI=1.05-1.38). In the subgroup analysis
      by ethnicity, significantly elevated risks were found among Asians (for CC versus
      TT: OR=1.61, 95% CI=1.37-1.89; for CC+TC versus TT: OR=1.36, 95% CI=1.16-1.60;
      for CC versus TT+TC: OR=1.44, 95% CI=1.22-1.70). In the subgroup analysis by
      study design, significantly increased risks were found among population-based
      case-control studies (for CC versus TT: OR=1.40, 95% CI=1.06-1.84; for CC+TC
      versus TT: OR=1.25, 95% CI=1.01-1.55; for CC versus TT+TC: OR=1.31, 95% CI=1.06
      1.61). These findings indicate that the FASLG -844C allele is emerging as a low
      penetrant cancer susceptibility allele for cancer development. However, more
      comprehensive understanding of the association would certainly have an immense
      prospect in the promising field of individualised preventive care.

PMID- 19403303
TI  - Additional value of MR/PET fusion compared with PET/CT in the detection of lymph
      node metastases in cervical cancer patients.
AB  - We evaluated the additional diagnostic value of magnetic resonance/positron
      emission tomography (MR/PET) fusion in the detection of metastatic lymph nodes in
      cervical cancer patients. Seventy nine patients with FIGO stage IB-IVA cervical
      cancer who had undergone both magnetic resonance imaging (MRI) and positron
      emission tomography/computed tomography (PET/CT) before lymphadenectomy were
      included in this study. Image analysis was first performed with PET/CT images
      only. A second analysis was then performed with MR/PET fused images that focused
      on the additional information obtained from the MR images. Lymphadenectomy
      involved removing all visible lymph nodes in the surgical field. To enable nodal
      group-specific comparisons, para-aortic and pelvic lymph nodes were divided into
      seven nodal groups: para-aortic, both common iliac, both external iliac and both
      internal iliac/obturator areas. Histopathological evaluation of lymph nodes has
      been the diagnostic standard. The value of the additional information from the MR
      images was evaluated by means of receiver operating characteristic (ROC)
      analysis. Fused MR/PET rendered readers to detect six more metastatic lymph node
      groups. The sensitivity and specificity of PET/CT and fused MR/PET were 44.1%,
      93.9% and 54.2%, 92.7% respectively. The ROC analysis demonstrated a higher
      diagnostic performance of fused MR/PET compared to PET/CT alone for detecting
      lymph node metastases (p=0.0259). The findings of this study demonstrate the
      additional diagnostic value of fused MR/PET images compared with PET/CT in the
      detection of metastatic lymph nodes in patients with uterine cervical cancer.

PMID- 19403302
TI  - Epigenetic down-regulation of BIM expression is associated with reduced optimal
      responses to imatinib treatment in chronic myeloid leukaemia.
AB  - BACKGROUND: Expression of the pro-apoptotic BCL-2-interacting mediator (BIM) has
      recently been implicated in imatinib-induced apoptosis of BCR-ABL1(+) cells.
      However, the mechanisms involved in the regulation of BIM in CML and its role in
      the clinical setting have not been established. DESIGN AND METHODS: We analysed
      the mRNA expression of BIM in 100 newly diagnosed patients with CML in chronic
      phase by Q-RT-PCR and the protein levels by Western blot analysis. Methylation
      status was analysed by bisulphite genomic sequencing and MSP. CML cell lines were
      treated with imatinib and 5-aza-2'-deoxycytidine, and were transfected with two
      different siRNAs against BIM and cell proliferation and apoptosis were analysed.
      RESULTS: We demonstrated that down-regulation of BIM expression was present in
      36% of the patients and was significantly associated with a lack of optimal
      response to imatinib as indicated by the decrease in cytogenetic and molecular
      responses at 6, 12 and 18 months in comparison with patients with normal BIM
      expression (p<0.05). Expression of BIM was mediated by promoter hypermethylation
      as demonstrated by restoration of BIM expression after treatment of CML cells
      with 5-aza-2'-deoxycytidine. Using CML cell lines with low and normal expression
      of BIM we further demonstrated that the expression of BIM is required for
      imatinib-induced CML apoptosis. CONCLUSION: Our data indicate that down
      regulation of BIM is epigenetically controlled by methylation in a percentage of
      CML patients and has an unfavourable prognostic impact, and that the combination
      of imatinib with a de-methylating agent may result in improved responses in
      patients with decreased expression of BIM.

PMID- 19403304
TI  - Enhanced production and partial characterization of an extracellular
      polysaccharide from newly isolated Azotobacter sp. SSB81.
AB  - A strain was selected by its highest extracellular polysaccharide (EPS)
      production ability compare to other isolates from the same rhizospheric soil. The
      selected strain was identified by 16S rDNA sequencing and designated as SSB81.
      Phylogenetic analysis of the gene sequence showed its close relatedness with
      Azotobacter vinelandii and Azotobacter salinestris. Maximum EPS (2.52 g l(-1))
      was recovered when the basal medium was supplemented with glucose (2.0%),
      riboflavin (1 mg l(-1)) and casamino acid (0.2%). The EPS showed a stable
      viscosity level at acidic pH (3.0-6.5) and the pyrolysis temperature was found to
      be at 116.73 degrees C with an enthalpy (DeltaH) of 1330.72 J g(-1). MALDI TOF
      mass spectrometric result suggests that polymer contained Hex(5)Pent(3) as
      oligomeric building subunit. SEM studies revealed that the polymer had a porous
      structure with small pore size distribution indicating the compactness of the
      polymer. This novel EPS may find possible application as a polymer for
      environmental bioremediation and biotechnological processes.

PMID- 19403305
TI  - Optimization of medium composition for butyric acid production by Clostridium
      thermobutyricum using response surface methodology.
AB  - The optimal medium for butyric acid production by Clostridium thermobutyricum in
      a shake flask culture was studied using statistical experimental design and
      analysis. The optimal composition of the fermentation medium for maximum butyric
      acid yield, as determined on the basis of a three-level four-factor Box-Behnken
      design (BBD), was obtained by response surface methodology (RSM). The high
      correlation between the predicted and observed values indicated the validity of
      the model. A maximum butyric acid yield of 12.05 g/l was obtained at K(2)HPO(4)
      7.2 g/l, 34.9 g/l glucose, 20 g/l yeast extract, and 15 g/l acetate, which
      compared well to the predicated production of 12.13 g/l.

PMID- 19403306
TI  - Characterization of cross-linked immobilized lipase from thermophilic mould
      Thermomyces lanuginosa using glutaraldehyde.
AB  - Cross-linked enzyme aggregates (CLEAs) have emerged as an interesting biocatalyst
      design for immobilization. Using this approach, a 1,3 regiospecific, alkaline and
      thermostable lipase from Thermomyces lanuginosa was immobilized. Efficient cross
      linking was observed when ammonium sulphate was used as precipitant along with a
      two fold increase in activity in presence of SDS. The TEM and SEM
      microphotographs of the CLEAs formed reveal that the enzyme aggregates are larger
      in size as compared to the free lipase due to the cross-linking of enzyme
      aggregates with glutaraldehyde. The stability and reusability of the CLEA with
      respect to olive oil hydrolysis was evaluated. The CLEA showed more than 90%
      residual activity even after 10 cycles of repeated use.

PMID- 19403307
TI  - A microwave-assisted facile regioselective Fischer indole synthesis and
      antitubercular evaluation of novel 2-aryl-3,4-dihydro-2H-thieno[3,2-b]indoles.
AB  - A series of novel 2-aryl-3,4-dihydro-2H-thieno[3,2-b]indoles has been synthesised
      regioselectively in good yields from the reaction of 5-aryldihydro-3(2H)
      thiophenones and arylhydrazine hydrochloride. This reaction is found to be
      assisted by microwaves. The thieno[3,2-b]indoles were evaluated for their in
      vitro activity against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug
      resistant M. tuberculosis (MDR-TB). Among 22 compounds screened, [2-(2,4
      dichlorophenyl)-7-fluoro-3,4-dihydro-2H-thieno[3,2-b]indole] (6t) was found to
      the most active compound with MIC of 0.4 microg/mL against MTB and MDR-TB.

PMID- 19403308
TI  - Discovery of novel spiro-piperidine derivatives as highly potent and selective
      melanin-concentrating hormone 1 receptor antagonists.
AB  - Optimization of high-throughput screening hit 1a led to the identification of a
      novel spiro-piperidine class of melanin-concentrating hormone 1 receptor (MCH-1R)
      antagonists. Compound 3c was identified as a highly potent and selective MCH-1R
      antagonist, which has an IC(50) value of 0.09 nM at hMCH-1R. The synthesis and
      structure-activity relationships of the novel spiro-piperidine MCH-1R antagonists
      are described.

PMID- 19403309
TI  - Fatigue and daytime sleepiness in patients with myotonic dystrophy type 1: to
      lump or split?
AB  - We assessed the relationship and clinical correlates of fatigue and Excessive
      Daytime Sleepiness (EDS) in 200 myotonic dystrophy type 1 (DM1) patients by means
      of questionnaire and neuropsychological evaluation. Fatigue levels were higher in
      patients with EDS and daytime sleepiness levels higher in patients with excessive
      fatigue. However, EDS without fatigue was rarely observed. Also, DM1 patients
      with fatigue (with or without EDS) showed greater muscular impairment, CTG
      repeats, abnormalities regarding personality, depressive symptoms and lower
      health-related quality of life (HRQoL) than patients without these symptoms.
      These findings do not readily support the contention that fatigue and EDS
      constitute distinct clinical manifestations in DM1. Clinicians should
      systematically evaluate both symptoms since fatigue and EDS have a greater impact
      on HRQoL than fatigue alone. However, specific rating scales for fatigue in DM1
      have yet to be devised.

PMID- 19403310
TI  - Changes in postural sway as a consequence of wearing a military backpack.
AB  - Military personnel are often required to carry all of their personal supplies and
      equipment for long distances during both training and combat situations, creating
      many biomechanical and postural challenges for these individuals. In addition to
      other problems such as generalized fatigue and the development of stress
      fractures, significant external loads may also affect a soldier's postural sway.
      The purpose of this study was to assess changes in postural sway as a consequence
      of wearing a military backpack in females. Forty-three female subjects between
      the ages of 18 and 25 volunteered to participate. There were two conditions:
      unloaded and while wearing an 18.1 kg military backpack. Each subject stood with
      two feet on a force platform for 30s under both conditions while center of
      pressure (COP) data were collected. COP path length increased 64%, medial-lateral
      excursion increased 131%, anterior-posterior excursion increased 54%, and COP
      area increased 229% with addition of the backpack (p<0.0001 for all of these
      measures). These data show that wearing 18.1 kg of external weight in a military
      backpack increases the postural sway of females, which may in turn increase the
      likelihood of falls and injury.

PMID- 19403312
TI  - A cadaver knee simulator to evaluate the biomechanics of rectus femoris transfer.
AB  - A cadaver knee simulator has been developed to model surgical transfer of the
      rectus femoris. The simulator allows knee specimens six degrees of freedom and is
      capable of modeling both the swing and stance phases of human gait. Experiments
      were conducted using a mechanical hinge analog of the knee to verify that time,
      flexion angle, and knee extension force measurements recorded when using the
      simulator were not influenced by its design or operation. A ballistic double
      pendulum model was used to model the swing phase of gait, and the contributions
      of hip and ankle torques and hamstrings cocontraction were included when modeling
      the stance phase of gait. When modeling swing, range of motion and time to peak
      knee flexion in swing for the hinge knee were similar to those of in vivo test
      subjects. Measurements of hinge knee extension force when modeling stance under
      various biomechanical conditions matched those predicted using an analytical
      model. Future studies using cadaver knee specimens will apply techniques
      described in this paper to further our understanding of changes in knee
      biomechanics caused by rectus femoris transfer surgery.

PMID- 19403311
TI  - Postural adaptation to unilateral hip muscle fatigue during human bipedal
      standing.
AB  - Although previous studies have investigated the effects of bilateral muscle
      fatigue on bipedal postural control, whether and how the central nervous system
      could adapt to unilateral muscle fatigue for controlling bipedal stance remains
      to be investigated. The purpose of the present experiment was designed to address
      this issue by assessing the effect of unilateral muscle fatigue induced on the
      hip's abductors of the dominant leg on bipedal standing. Twenty-four young
      healthy adults stood barefoot, feet together, with their eyes closed and were
      asked to sway as little as possible. The experimental group (n=12) executed this
      postural task in two conditions, pre- and post-fatigue. In the post-fatigue
      condition, the measurements were performed immediately after a designated
      fatiguing exercise for the hip abductors of their dominant leg. For the control
      group (n=12), this fatiguing exercise was replaced by a laying rest period
      corresponding to the fatiguing exercise. The distribution of the body weight and
      plantar centre of foot pressure (CoP) displacements from the non-fatigued and
      fatigued leg were recorded along the mediolateral and anteroposterior axes using
      a plantar pressure data acquisition system. Results of the experimental group
      showed that unilateral muscle fatigue induced on the hip's abductors of the
      dominant leg had different effects on the plantar CoP displacements (1) under the
      non-fatigued and fatigued legs, yielding larger displacements under the non
      fatigued leg only, and (2) in the anteroposterior and mediolateral axes, yielding
      larger displacements along the mediolateral axis only. These observations could
      not be accounted for by any asymmetrical distribution of the body weight on both
      legs which were similar for both pre- and post-fatigue conditions. The observed
      postural responses could be viewed as an adaptive process to cope with an
      unilateral alteration in the hip neuromuscular function induced by the fatiguing
      exercise for controlling bipedal stance. The increase in CoP displacements
      observed under the non-fatigued leg in the fatigue condition could reflect
      enhanced exploratory "testing of the ground" movements with sensors of the non
      fatigued leg's feet, providing supplementary somatosensory inputs to the central
      nervous system to preserve/facilitate postural control in condition of altered
      neuromuscular function of the dominant leg's hip abductors induced by the
      fatiguing exercise.

PMID- 19403313
TI  - ACE inhibitors hypothesis generation for selective design, synthesis and
      biological evaluation of 3-mercapto-2-methyl-propanoyl-pyrrolidine-3-imine
      derivatives as antihypertensive agents.
AB  - A series of new 3-mercapto-2-methyl-propanoyl-pyrrolidine derivatives (V, VIa-e)
      were designed. A new validated ACE inhibitors pharmacophore model (hypothesis)
      was generated for the first time in this research from the biologically active
      (frozen) conformation of Lisinopril-Human ACE complex that was downloaded from
      PDB, using stepwise technique of CATALYST modules. The molecular modeling compare
      fit study of the designed molecules (V, VIa-e), with such ACE inhibitors
      hypothesis was fulfilled, and several compounds showed significant high
      simulation fit values. The compounds with high fit values were synthesized and
      biologically evaluated in vivo as hypotensive agents. It appears that the in vivo
      hypotensive activity of compounds V, VIa, VIb, and VIe was consistent with their
      molecular modeling results, and compound VIe showed the highest activity in
      comparison to Captopril.

PMID- 19403314
TI  - New antituberculotics originated from salicylanilides with promising in vitro
      activity against atypical mycobacterial strains.
AB  - A new series of 30 N-protected amino acid esters were prepared as a part of
      ongoing search for new anti-tuberculosis active salicylanilides. The esters
      possess high in vitro activity against Mycobacterium tuberculosis, Mycobacterium
      avium, and two strains of Mycobacterium kansasii, where one is an isolate from
      the patient, with MIC in the range 1-32 micromol/L for all tested strains. The
      prepared esters can be considered as prodrugs with better bio-availability and as
      more efficient transport forms through the mycobacterial cell membranes due to
      the higher lipophilicity. The experimental and calculated lipophilicity,
      stability, antituberculotic activity, cytotoxicity as well as the quantitative
      structure-activity relationships (QSARs) explored by the Intelligent Problem
      Solver (IPS) in Trajan Neural Network Simulator 6.0 are presented.

PMID- 19403315
TI  - Electrolyte disorders related to EGFR-targeting drugs.
AB  - It is now clearly established that anti-vascular endothelial growth factor (VEGF)
      drug class induces hypertension and proteinuria sometimes related to thrombotic
      microangiopathy and/or various glomerulopathies, according to capillary and
      glomerular VEGF and VEGF-receptor expressions. As reported in the literature,
      anti-epidermal growth factor receptor (EGFR) therapies seem to be less
      nephrotoxic. Indeed, many reports of anti-EGFR nephrotoxicity are tubular
      dependent such as acute tubular necrosis, electrolyte disorders
      (hypophosphatemia, hypomagnesemia, etc.) or both. This is explained by elective
      tubular expression of renal EGF/EGFR. In this paper, we focus on electrolyte
      disorders related to anti-EGFR treatment and discuss the tubular involvement of
      these drugs based on their renal expression.

PMID- 19403316
TI  - Optimized Orbitrap HCD for quantitative analysis of phosphopeptides.
AB  - Despite the tremendous commercial success of radio frequency quadrupole ion traps
      for bottom-up proteomics studies, there is growing evidence that peptides
      decorated with labile post-translational modifications are less amenable to low
      energy, resonate excitation MS/MS analysis. Moreover, multiplexed stable isotope
      reagents designed for MS/MS-based quantification of peptides rely on accurate and
      robust detection of low-mass fragments for all precursors. Collectively these
      observations suggest that beam-type or tandem in-space MS/MS measurements, such
      as that available on traditional triple quadrupole mass spectrometers, may
      provide beneficial figures of merit for quantitative proteomics analyses. The
      recent introduction of a multipole collision cell adjacent to an Orbitrap mass
      analyzer provides for higher energy collisionally activated dissociation (HCD)
      with efficient capture of fragment ions over a wide mass range. Here we describe
      optimization of various instrument and post-acquisition parameters that
      collectively provide for quantification of iTRAQ-labeled phosphorylated peptides
      isolated from complex cell lysates. Peptides spanning a concentration dynamic
      range of 100:1 are readily quantified. Our results indicate that appropriate
      parameterization of collision energy as a function of precursor m/z and z
      provides for optimal performance in terms of peptide identification and relative
      quantification by iTRAQ. Using this approach, we readily identify activated
      signaling pathways downstream of oncogenic mutants of Flt-3 kinase in a model
      system of human myeloid leukemia.

PMID- 19403317
TI  - Epithelial salivary tumors in Sri Lanka: a retrospective study of 713 cases.
AB  - OBJECTIVE: The aim of this retrospective study was to evaluate the
      clinicopathologic data to determine the distribution of epithelial salivary
      tumors, especially minor salivary tumors, in Sri Lanka. MATERIALS AND METHODS: A
      total of 713 salivary tumors diagnosed at the Department of Oral Pathology,
      during the period from 1990 to 2007 were reviewed. RESULTS: Out of the 713
      epithelial salivary tumors, 356 (49.9%) were classified as benign and 357 (50.1%)
      as malignant, indicating a benign-to-malignant ratio of 1:1. The majority of both
      benign (29%) and malignant (39%) tumors occurred in the minor salivary glands.
      Malignant tumors were slightly more common in minor salivary glands, indicating a
      benign-to-malignant ratio of 1:0.75. Among the minor salivary sites, palate was
      the most frequent location, accounting for 51% of the tumors (246 out of 486).
      The tumors affected adult patients more commonly, and a slight female
      predominance (1:1.15) was also evident. Pleomorphic adenoma was the most frequent
      tumor, representing 38% of all tumors (274 out of 713), followed by
      mucoepidermoid carcinoma 21.6% (154 out of 713) and adenoid cystic carcinoma
      13.5% (96 out of 713). The commonest benign and malignant tumors were pleomorphic
      adenoma and mucoepidermoid carcinoma in both major and minor salivary glands.
      CONCLUSION: According to the findings of this study, equal frequencies of benign
      and malignant tumors indicate higher occurrences of malignancies, especially in
      the minor salivary glands, in the Sri Lankan population.

PMID- 19403318
TI  - Comment on: chronic pain: avoidance or endurance? by Petra Karsdorp and Johan
      Vlaeyen.

PMID- 19403319
TI  - Ab initio molecular orbital calculations on specific interactions between
      urokinase-type plasminogen activator and its receptor.
AB  - Cancer invasions and metastases are controlled by various proteases. In
      particular, the binding of urokinase-type plasminogen activator (uPA) to the uPA
      receptor (uPAR) existing on the surface of cancer cell is considered to be a
      trigger for cancer invasions. In the present study, we determined the structure
      of uPA and uPAR complex in water and investigated the specific interactions
      between uPA and uPAR by ab initio molecular orbital (MO) calculations based on
      fragment MO method. The result indicates that the 20-26 amino acid residues of
      uPA are important for the binding between uPA and uPAR, and that the
      electrostatic interactions between the charged amino acid residues existing in
      both uPA and uPAR have large contribution to the binding. The influence of
      crystal water molecules existing between uPA and uPAR was also investigated to be
      significant on the specific interactions between uPA and uPAR. These results are
      expected to be informative for developing new medicines blocking the binding of
      uPA and uPAR.

PMID- 19403320
TI  - Disseminated bacille Calmette-Guerin in Iranian children with severe combined
      immunodeficiency.
AB  - BACKGROUND: The bacille Calmette-Guerin (BCG) vaccine is a widely practiced
      vaccine, which is useful for prophylaxis against tuberculosis. Disseminated BCG
      infection (BCG-osis) is one of the most important complications of this vaccine
      and can be seen in patients with an underlying immunodeficiency. This study was
      performed to determine the underlying defects in patients with BCG-osis. METHODS:
      Immunological evaluation was performed in all children who developed BCG-osis
      after vaccination in Tabriz, Iran. RESULTS: BCG-osis was documented in eight
      patients following vaccination. Axillary adenitis was detected in seven patients,
      and hepatosplenomegaly was also found in seven patients. Immunological studies
      revealed low serum IgG, IgM and IgA levels in all patients. Further
      investigations for enumeration of the lymphocyte sub-population revealed severe
      combined immunodeficiency (SCID) in all the patients. Three patients had T-B+NK-
      SCID, four had T-B-NK+ SCID, and one had T-B+NK+ SCID. Unfortunately, all the
      patients died due to the severe disseminated BCG infection. CONCLUSIONS:
      Inoculation of live vaccines such as BCG should be postponed for a few months in
      suspected cases of primary immunodeficiency disease, until appropriate screening
      tests exclude this diagnosis; vaccination should then be performed in those with
      an intact immune system.

PMID- 19403321
TI  - [Response of D. Gallot et al to the article of J.-P. Pelage and O. Limot. Role of
      arterial embolization in the care of serious hemorrhages immediately postpartum.
      Gynecol Obstet Fertil 2008;36:714-20].

PMID- 19403322
TI  - [Retrospective study conducted in northern Finistere about the role of breast MRI
      in normal breast screening, experience in 51 patients].
AB  - OBJECTIVES: To study the role and indications of breast MRI in normal breast
      screening. PATIENTS AND METHODS: Retrospective study of 51 patients (mean age of
      51 years) conducted in northern Finistere. Each patient had a normal (BI-RADS 1
      or 2) breast screening (mammography and echography). Four indications for MRI
      were chosen: screening of high-risk patients, high-density breasts, radio
      clinical discordance, and breasts prostheses. Breast MRI were reviewed according
      to BI-RADS classification. Abnormalities categorized in BI-RADS 4 or 5 were
      confirmed histologically. RESULTS: Thirteen patients underwent histological
      analysis. Nine invasive carcinomas were identified (six invasive lobular
      carcinomas (ILC), two mixed carcinomas, one invasive ductal carcinoma). For these
      patients, the reason for performing MRI was a radio-clinical discordance.
      DISCUSSION AND CONCLUSION: The study demonstrates the breast MRI value for radio
      clinical discordance and the key role of MRI in diagnostic challenge of ILC. In
      literature review, MRI has a role even if breast screening is normal: radio
      clinical discordance, screening of patients with high-risk, breasts prostheses in
      certain cases. Breast density comes as an additional criteria to perform this
      exam.

PMID- 19403323
TI  - Analysis of ionic ratios in the interventricular wall and their relation with
      cardiac damage as seen in anatomo-pathological and cardiac biomarkers.
AB  - In the present work, we have compared the behaviour of some commonly used markers
      for the immunohistochemical diagnosis of cardiac suffering (myoglobin, myosin,
      troponin I), with the modifications of the ionic quotients (K(+)/Na(+),
      Ca(2+)/Mg(2+) and Ca(2+)/Zn(2+)) that are observed in the interventricular
      partition in different causes of death. MATERIALS AND METHOD: we have studied a
      total of 50 hearts coming from autopsies carried out in the Legal Medicine
      Institute of Murcia (Spain) deceased 21 by natural cardiac deaths, 9 by
      mechanical asphyxias, 5 by politraumatism, 5 cardiac ruptures and 10 by
      craneoencephalic trauma. For the biochemical analysis, samples were taken from
      weave of 0.5 g of the interventricular partition, the corresponding dilutions
      were made in bidistilled water for flame atomic absorption spectrophotometry with
      a hollow cathode multielement lamp. For the immunohistochemical study, samples
      were taken from the same locations, kept in tamponed formol, dyed with
      hematoxylin-eosin and later 3 microm-sections were practised, antigenic recovery
      by heat, in pressure cooker. Our results show the existence of a statistically
      significant relation between the modifications of the K(+)/Na(+) quotient and the
      found values of troponin, which confirms its utility for the precocious diagnosis
      of the cardiac ischemia.

PMID- 19403324
TI  - Effect of the calculation methods on body moment of inertia estimations in
      individuals of different morphology.
AB  - Body segment moments of inertia (MOI) are estimated from data obtained from
      cadavers or living individuals. Though these methods can be valid for the general
      population, they usually are limited when applied to special populations (e.g.,
      obese). The effect of two geometric methods, photogrammetry and two new methods,
      namely, inverse dynamics and angular momentum on the estimations of MOI in
      individuals of different body mass index (BMI) were compared to gain insight into
      their relative accuracy. The de Leva (1996) method was chosen as a criterion to
      determine how these methods behaved. MOI methods were not different in
      individuals with a normal BMI. On the average, MOI values obtained with inverse
      dynamics and angular momentum were respectively 13.2% lower for lean participants
      and 17.9% higher for obese subjects than those obtained from the de Leva method.
      The average Pearson coefficients of correlation between the MOI values, estimated
      by the de Leva method, and the other methods was 0.76 (+/-0.31). Since the
      proposed methods made no assumption on the mass distribution and segments'
      geometry, they appeared to be more sensitive to body morphology changes to
      estimate whole body MOI values in lean and obese subjects.

PMID- 19403325
TI  - Long-term effects of bilateral deep brain stimulation of the subthalamic nucleus
      on depression in patients with Parkinson's disease.
AB  - OBJECTIVE: To study the long-term effects of deep brain stimulation (DBS) of the
      bilateral subthalamic nucleus (STN) on depression in patients with Parkinson's
      disease (PD) and to discuss the mechanism. METHODS: A STN-DBS group (n = 27) and
      anti-Parkinson's medication control group with paired designing were set up. The
      evaluation of the depression and motor function was performed a total of six
      times. Depression was evaluated by the Self-Rating Depression Scale (SDS) and
      Hamilton Rating Scale for Depression (HAMD). Motor function was evaluated by the
      third part of the Unified Parkinson's Disease Rating Scale (UPDRS-III). RESULTS:
      Compared with the preoperative and the medication control group, the UPDRS-III
      scores of the STN-DBS group decreased remarkably within 18 months postoperatively
      (P < or = 0.001), and the SDS scores decreased notably within 6 months
      postoperatively (P < or = 0.05), and the HAMD scores decreased notably within 3
      months postoperatively (P < or = 0.05). The UPDRS-III scores were strongly
      correlated with their SDS scores within 6 months postoperatively (P < or = 0.05),
      especially at 5 weeks postoperation (P < or = 0.001). UPDRS-III scores were also
      strongly correlated with HAMD scores at 5 weeks postoperation (P < or = 0.05).
      The mean value of the bilateral voltages was obviously correlated with SDS and
      HAMD scores (P < or = 0.05) within 18 months postoperatively. CONCLUSION: The
      improvement in motor symptoms resulting from STN-DBS can improve depression in PD
      patients, but its long-term effects were unremarkable. Within the treatment
      range, the higher the mean value of bilateral voltages then the more severe was
      the depression in PD patients.

PMID- 19403326
TI  - Do perceived neighbourhood cohesion and safety contribute to neighbourhood
      differences in health?
AB  - This paper reports on a survey (N=3344) and in-depth interviews (N=80) from four
      socio-economically contrasting postcode areas in Adelaide. Logistic regression
      was used to examine locational differences in self-rated health, controlling for
      demographic, socio-economic factors, health behaviours, individual social capital
      (social networks, support, reciprocity, trust) and perceived neighbourhood
      cohesion and safety. Statistically significant locational differences in health
      emerged. Perceived neighbourhood cohesion and safety accounted for this
      difference. Interviews explored perceptions of cohesion and safety and found that
      they were intricately related and varied between the areas. The implications of
      the findings for understanding locational differences in health are discussed.

PMID- 19403327
TI  - Much ado about eye movements to nothing: a response to Ferreira et al.: taking a
      new look at looking at nothing.

PMID- 19403328
TI  - Synthesis and spectral characterization of 14- and 16-membered
      tetraazamacrocyclic Schiff base ligands and their transition metal complexes and
      a comparative study of interaction of calf thymus DNA with copper(II) complexes.
AB  - 14 and 16 membered Schiff base macrocyclic ligands, 7,14-dimethyl-5,12-di(N
      amino)-2-methylphenyl-1,4,8,11-tetraaza-cyclotetradecane-4,7,11,14-tetraene
      (L(1)) and 8,16-dimethyl-6,14-di(N-amino)-2-methylphenyl-1,5,9,13-tetraaza
      cyclohexadecane-5,8,13,16-tetraene (L(2)) were synthesized by condensation
      reaction between 2'-methyleacetoacetanilide and aliphatic diamines. The metal
      complexes of the types, [ML(1)](NO(3))(2) and [ML(2)(NO(3))(2)] [M = Co(II),
      Ni(II), Cu(II) and Zn(II)] were prepared by interaction of ligands, L(1) or L(2)
      with hydrated metal(II) nitrates. The ligands and their complexes were
      characterized by elemental analysis, IR, (1)H and (13)C NMR, EPR, UV-Vis
      spectroscopy, magnetic susceptibility, conductivity measurements and ESI-mass
      spectral studies. The results of elemental analyses, ESI-mass and conductivity
      measurements confirmed the stoichiometry of ligands and their complexes while the
      characteristic absorption bands and resonance peaks in IR and NMR spectra
      confirmed the formation of ligand frameworks around the metal ions. The square
      planar geometry for complexes derived from ligand L(1) and octahedral environment
      for complexes derived from ligand L(2) with distortion in Cu(II) complex have
      been confirmed on the basis of results of electronic and electron spin resonance
      spectral studies and magnetic moment measurements. Absorption and fluorescence
      spectral studies revealed different binding mode for complex, [CuL(1)](NO(3))(2)
      as compared with [CuL(2)(NO(3))(2)] on interaction with calf thymus DNA.

PMID- 19403329
TI  - Safety limits of cathodal transcranial direct current stimulation in rats.
AB  - OBJECTIVE: The aim of this rat study was to investigate the safety limits of
      extended transcranial direct current stimulation (tDCS). tDCS may be of
      therapeutic value in several neuro-psychiatric disorders. For its clinical
      applicability, however, more stable effects are required, which may be induced by
      intensified stimulations. METHODS: Fifty-eight rats received single cathodal
      stimulations at 1-1000 microA for up to 270 min through an epicranial electrode
      (3.5 mm(2)). Histological evaluation (H&E) was performed 48 h later. A threshold
      estimate was calculated from volumes of DC-induced lesions. RESULTS: Brain
      lesions occurred at a current density of 142.9 A/m(2) for durations greater than
      10 min. For current densities between 142.9 and 285.7 A/m(2), lesion size
      increased linearly with charge density; with a calculated zero lesion size
      intercept of 52,400 C/m(2). Brains stimulated below either this current density
      or charge density threshold, including stimulations over 5 consecutive days, were
      morphologically intact. CONCLUSION: The experimentally determined threshold
      estimate is two orders of magnitude higher than the charge density currently
      applied in humans (171-480 C/m(2)). In relation to transcranial DC stimulation in
      humans the rat epicranial electrode montage may provide for an additional safety
      margin. SIGNIFICANCE: Although these results cannot be directly transferred to
      humans, they encourage the development intensified tDCS protocols. Further animal
      studies are required, before such protocols can be applied in humans.

PMID- 19403330
TI  - The impact of chronic primary insomnia on the heart rate--EEG variability link.
AB  - OBJECTIVE: To determine if chronic insomnia alters the relationship between heart
      rate variability and delta sleep determined at the EEG. METHODS: After one night
      of accommodation, polysomnography was performed in 14 male patients with chronic
      primary insomnia matched with 14 healthy men. ECG and EEG recordings allowed the
      determination of High Frequency (HF) power of RR-interval and delta sleep EEG
      power across the first three Non Rapid Eye Movement (NREM)-REM cycles.
      Interaction between normalized HF RR-interval variability and normalized delta
      sleep EEG power was studied by coherency analysis. RESULTS: Patients showed
      increased total number of awakenings, longer sleep latency and wake durations and
      shorter sleep efficiency and REM duration than controls (p<.01). Heart rate
      variability across first three NREM-REM cycles and sleep stages (NREM, REM and
      awake) were similar between both groups. In each group, normalized HF variability
      of RR-interval decreased from NREM to both REM and awake. Patients showed
      decreased linear relationship between normalized HF RR-interval variability and
      delta EEG power, expressed by decreased coherence, in comparison to controls
      (p<.05). Gain and phase shift between these signals were similar between both
      groups. CONCLUSIONS: Interaction between changes in cardiac autonomic activity
      and delta power is altered in chronic primary insomniac patients, even in the
      absence of modifications in heart rate variability and cardiovascular diseases.
      SIGNIFICANCE: This altered interaction could reflect the first step to
      cardiovascular disorders.

PMID- 19403331
TI  - Epidemiology of restless legs syndrome in Turkish adults on the western Black Sea
      coast of Turkey: A door-to-door study in a rural area.
AB  - OBJECTIVE: To determine the prevalence and clinical presentation of restless legs
      syndrome (RLS) in Turkish population living in Kandira, a town located on the
      Black Sea coast of Istanbul. METHODS: This study was designed as a descriptive,
      cross-sectional, door-to-door field study. A total of 2111 people aged 18 years
      and over were selected for the study. The criteria suggested by the IRLSSG
      (International Restless Legs Syndrome Study Group) were used in the assessment of
      RLS. All the suspected subjects underwent neurological examination. RESULTS: The
      prevalence of RLS was found to be 3.4% of Turkish population aged over 18.
      Female:male ratio was 3.5:1. The prevalence reached peak point (8.3%) in the 58-
      to 67-year-old group. Prevalence of DM, anemia and polyneuropathy in RLS patients
      was 13.9%, 8.3% and 4.2%, respectively. CONCLUSION: RLS prevalence is relatively
      low, but increases with age in both genders in this Turkish population. Although
      it has negative effects on daily life, it is not well recognized by the
      population.

PMID- 19403332
TI  - Sleep deprivation worsens inflammation and delays recovery in a mouse model of
      colitis.
AB  - BACKGROUND AND AIM: We recently showed that patients with inflammatory bowel
      disease (IBD) report significantly more sleep disturbances. To determine whether
      disrupted sleep can affect the severity of inflammation and the course of IBD, we
      used an animal model of colonic inflammation to determine the effects of acute
      and chronic intermittent sleep deprivation on the severity of colonic
      inflammation and tissue damage in colitis and recovery from this damage. METHODS:
      Acute sleep deprivation (ASD) consisted of 24h of forced locomotor activity in a
      mechanical wheel rotating at a constant speed. Chronic intermittent sleep
      deprivation (CISD) consisted of an acute sleep deprivation episode, followed by
      additional sleep deprivation periods in the wheel for 6h every other day
      throughout the 10day study period. To induce colitis, mice were given 2% dextran
      sodium sulfate (DSS) in their daily drinking water for 7days. The development and
      severity of colitis were monitored by measuring weight loss and tissue
      myeloperoxidase (MPO) activity daily and colon histology scores 10days after
      initiation of colitis. RESULTS: ASD or CISD did not cause colonic inflammation in
      vehicle-treated mice. Changes in daily body weight, tissue MPO levels and colon
      histopathology score were similar between mice that were sleep deprived and
      controls. Daily DSS ingestion caused colitis in mice. ASD worsened colonic
      inflammation: tissue MPO levels in ASD/DSS-treated mice were significantly higher
      than in DSS-treated mice that were not sleep deprived. However, the worsening of
      colonic inflammation by ASD was not enough to exacerbate clinical manifestations
      of colitis such as weight loss. In contrast, the deleterious effects of CISD were
      severe enough to cause worsening of histological and clinical manifestations of
      colitis. The deleterious effects of sleep deprivation on severity of colitis
      appeared to be due to both increased colonic inflammation and a decrease in the
      ability of mice to recover from DSS-induced colonic injury. CONCLUSION: Both
      acute and chronic intermittent sleep deprivation exacerbate colonic inflammation.
      Thus, sleep deprivation could be an environmental trigger that predisposes IBD
      patients to develop flare ups and a more severe disease course. These results
      provide a scientific rationale to conduct an interventional trial to determine
      whether improvement in sleep patterns will prevent IBD flare ups, modify the
      disease course, and improve quality of life.

PMID- 19403333
TI  - Gender differences in the clinical manifestation of obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) has been historically described as a disease
      primarily of men. However, it is now widely recognized that OSA in women is not
      as rare as was originally believed. The alarming degree to which OSA is
      clinically underdiagnosed in women raises the critical concern that women
      manifest OSA differently. The purpose of this review is to examine the issue of
      clinically significant gender differences in OSA disease manifestation, which
      pose unique challenges to diagnosis and management. Within this review, current
      findings regarding gender differences in OSA polysomnographic features and
      demographic factors, symptom presentation, functional status, comorbidities,
      health care utilization, and therapeutic management have been reviewed. Further
      research in this field is proposed to examine the impact of gender on functional
      status in individuals with OSA, and the potential gender differences in
      therapeutic management, particularly the response to continuous positive airway
      pressure (CPAP) treatment. Additional studies describing the clinical
      manifestations in men and women at different levels of OSA severity may
      substantially contribute to the ability to identify and treat OSA in women across
      a wide spectrum of disease severity.

PMID- 19403334
TI  - Sleep and gastrointestinal disease: a new horizon in sleep medicine.

PMID- 19403335
TI  - Pediatric single-port-access nephrectomy for a multicystic, dysplastic kidney.
AB  - Major urologic surgery via a single port has emerged as the latest progression in
      laparoscopy and robotics. While current literature highlights the single-port
      approach to the surgical treatment of cholecystitis, appendicitis and
      varicoceles, this technique has never been employed to perform a nephrectomy on a
      child. We herein report a case of a pediatric patient who underwent nephrectomy
      via single-port-access.

PMID- 19403337
TI  - Could natural killer cells compensate for impaired CD4+ T-cell responses to CMV
      in HIV patients responding to antiretroviral therapy?
AB  - We evaluated NK cell subsets and functions in previously immunodeficient HIV
      patients responding to ART. Cytokine receptor mRNA was quantitated in purified
      CD56+ cells. Data were correlated with CD4+ T-cell counts and IFNgamma responses
      to CMV. NK cell IFNgamma responses to K562 cells and proportions of CD56lo NK
      cells were correlated in patients (p < 0.001) and both were lower than in
      controls (p < 0.001 and p = 0.008, respectively), so all patients had poor NK
      cell function. Proportions of CD56hi NK cells correlated inversely with current
      CD4+ T-cell counts (p = 0.006) and perforin expression in CD56hi NK cells was
      higher in patients than controls (p < 0.05). Hence increased proportions and
      cytolytic function of CD56hi NK cells may partially compensate for CD4+ T-cell
      deficiency. NK cell IFNgamma responses correlated inversely with expression of IL
      10 and IL-12 receptor mRNA. Expression of these transcripts is reduced by
      exposure to the cytokines, which may reflect immune activation in immunodeficient
      patients.

PMID- 19403338
TI  - Characterising acute gynaecological pathology with ultrasound: an overview and
      case examples.
AB  - This article summarises the ultrasound features of a number of gynaecological
      emergencies: ectopic pregnancy, haemorrhagic corpus luteum, twisted adnexa,
      pelvic inflammatory disease, acute myoma necrosis, haematocolpos and
      haematometra. The basis of all diagnosis in women with acute gynaecological
      conditions is history and clinical examination. An ultrasound examination should
      only be performed if it is likely to provide information that would change the
      likelihood of the diagnosis suspected on the basis of clinical data. If
      ultrasound findings are abnormal, then it is important to thoroughly evaluate if
      they do explain the woman's symptoms or if they are merely an incidental finding.
      If ultrasound findings are completely normal, then the risk of significant pelvic
      pathology is probably small.

PMID- 19403336
TI  - Breaking old paradigms: Th17 cells in autoimmune arthritis.
AB  - Aberrant helper T cell activation has been implicated in the pathogenesis of an
      array of autoimmune diseases. In this review, we summarize evidence that suggests
      the involvement of a novel T cell subset, the Th17 lineage, in rheumatoid
      arthritis. In particular, we focus on the role of Th17 cells in inducing and
      perpetuating the chronic inflammation, cartilage damage, and bone erosion that
      are hallmark phases of joint destruction and consider current and emerging
      therapies that seek to disrupt the inflammatory Th17 network and shift the immune
      system back towards homeostasis.

PMID- 19403339
TI  - Symbolic analysis detects alterations of cardiac autonomic modulation in
      congestive heart failure rats.
AB  - Congestive heart failure (CHF) is associated with neurohumoral activation. Only
      very few studies have examined the progression of autonomic dysfunction in CHF in
      humans and scanty data are available in animal models of CHF. This study was
      performed to assess the changes in cardiac autonomic modulation during the
      progression of CHF in a rat model, using an innovative analysis of heart rate
      variability. Progression of cardiovascular autonomic dysfunction was assessed in
      a rat model of CHF induced by coronary artery ligation. Spectral and symbolic
      analyses were performed on heart period (approximated with pulse interval, PI)
      and systolic arterial pressure (SAP) signals, acquired ~2 and ~4 weeks after the
      surgical procedure. As CHF developed, symbolic analysis revealed a decrease of
      rhythmical physiological sympathetic modulation, as indicated by the reduction of
      the percentage of stable patterns. In addition, symbolic analysis revealed that
      runs of short-long-short and/or long-short-long PI values and high-low-high
      and/or low-high-low SAP values were more and more frequent as CHF progressed. On
      the contrary, spectral analysis of PI and SAP series was not able to detect any
      impairment of autonomic regulation. Indeed, low frequency and high frequency
      powers derived from both PI and SAP series were not significantly changed. These
      data indicate that the autonomic cardiovascular modulation is altered during the
      progression of CHF and that symbolic analysis seems to be more suitable than
      spectral analysis to describe alterations of heart period dynamics and of
      cardiovascular regulation in this animal model of CHF.

PMID- 19403340
TI  - Differential control of MMP and t-PA/PAI-1 expressions by sympathetic and renin
      angiotensin systems in rat left ventricle.
AB  - In the present study, we tested the hypothesis that angiotensin II (Ang II) has
      both direct (via AT1 receptors) and indirect (via sympathostimulator pathway)
      actions on the synthesis and activity of the enzymes involved in the
      extracellular matrix degradation in vivo. For this purpose, sympathectomy and
      blockade of the Ang II receptor AT1 were performed alone or in combination in
      normotensive rats. The mRNA of the plasminogen activator (t-PA) and its inhibitor
      (PAI-1), the mRNA, protein and activity of the matrix metalloproteinases MMP-2
      and MMP-9 were examined by Q-RT-PCR, immunoblotting and zymographic methods in
      the left ventricle. t-PA and PAI-1 mRNA were decreased after sympathectomy and
      remained unchanged after AT1 receptors blockade. mRNA was increased for t-PA and
      decreased by similar degree for PAI-1 after double treatment. MMPs mRNA and
      protein levels were decreased either after sympathectomy or AT1 receptors
      blockade and an additive effect was acquired after double treatment. MMPs
      activity was decreased by similar degree in the three treated groups. Deducted
      interpretations from our experimental approach suggest that Ang II inhibits
      directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) t-PA
      mRNA synthesis. It seems unable to influence directly PAI-1 mRNA, but stimulates
      indirectly PAI-1 mRNA synthesis. Ang II stimulates directly (via AT1 receptors)
      and indirectly (via sympathostimulator pathway) MMPs synthesis at both
      transcriptional and protein levels. The enzymatic activity of MMPs does not seem
      to be influenced directly by Ang II but it could be stimulated indirectly (via
      sympathostimulator pathway).

PMID- 19403341
TI  - Effect of mood during daily life on autonomic nervous activity balance during
      subsequent sleep.
AB  - RR-interval and eight types of mood level were recorded for 48 h from 40 normal
      male subjects. Sympathovagal balance was evaluated by calculating the normalized
      high-frequency power (HFnu) of RR-interval variability. The mean mood levels
      during 6 h before bedtime and the mean HFnu during 3 h after bedtime were
      compared. The data were normalized individually and the differences from the
      first night (Deltamood and DeltaHFnu) were taken. The correlation coefficient
      between Deltadepression and DeltaHFnu was -0.53, and that between Deltaworry and
      DeltaHFnu was -0.44. This implies that both daily depression and worry shift
      toward sympathetic dominance during subsequent sleep.

PMID- 19403342
TI  - Designing nanomaterial-enhanced electrochemical immunosensors for cancer
      biomarker proteins.
AB  - Detection of multiple cancer biomarker proteins in human serum and tissue at
      point-of-care is a viable approach for early cancer detection, but presents a
      major challenge to bioanalytical device development. This article reviews recent
      approaches developed in our laboratories combining nanoparticle decorated
      electrodes and multilabeled secondary antibody labeled particles to achieve high
      sensitivity for the detection of cancer biomarker proteins. Two nanomaterial
      based sensor platforms were used: (a) upright single wall carbon nanotube forests
      and (b) layers of densely packed 5 nm gold nanoparticles. Both platforms feature
      pendant carboxylate groups for easy attachment of enzymes or antibodies by
      amidization. In quality performance tests, the biocatalytic responses for
      determination of hydrogen peroxide of AuNP layers with attached horseradish
      peroxidase (HRP) on electrodes gave somewhat better detection limit and
      sensitivity than single wall carbon nanotube (SWNT) forest platforms with HRP
      attached. Evaluation of these sensors as platforms for sandwich immunoassays for
      cancer biomarker prostate specific antigen (PSA) in serum showed that both
      approaches gave accurate results for human serum samples from cancer patients.
      The best detection limit (0.5 pg mL(-1)) and sensitivity were obtained by
      combining the AuNP immunosensors with binding of 1 mum diameter magnetic
      particles decorated with secondary antibodies and 7500 HRP labels.

PMID- 19403343
TI  - Immobilized metal affinity chromatography in open-loop simulated moving bed
      technology: purification of a heat stable histidine tagged beta-glucosidase.
AB  - Open-loop simulated moving bed (SMB) has been used for immobilized metal affinity
      chromatographic (IMAC) purification of his-tagged beta-glucosidase expressed in
      E. coli. A simplified approach based on an optimized single column protocol is
      used to design the open-loop SMB. A set of columns in the SMB represent one step
      in the chromatographic cycle i.e. there will be one set each of columns for load,
      wash, elution etc within the SMB. Only the wash and elution are operated with
      columns in sequence. The beta-glucosidase was purified to almost single band
      purity with a purification factor of 15 and a recovery of 91%. SMB-performance
      showed reduced buffer consumption, higher purification fold, a better yield and
      higher productivity.

PMID- 19403344
TI  - Full sequencing of TP53 identifies identical mutations within in situ and
      invasive components in breast cancer suggesting clonal evolution.
AB  - In breast cancer, previous studies have suggested that somatic TP53 mutations are
      likely to be an early event. However, there are controversies regarding the
      cellular origin and linear course of breast cancer. The purpose of this study was
      to investigate tumor evolution in breast cancer by analyzing TP53 mutation status
      in tumors from various stages of the disease. The entire coding sequence of TP53
      was sequenced in a cohort of pure ductal carcinoma in situ (DCIS), pure invasive
      cancer (<=15mm) and mixed lesions (i.e. invasive cancer with an in situ
      component). Of 118 tumor samples, 19 were found to harbor a TP53 mutation; 5
      (15.6%) of the pure DCIS, 4 (10.5%) of the pure invasive cancers and 10 (20.8%)
      of the mixed lesions. In the mixed lesions, both the invasive and the DCIS
      components showed the same mutation in all 5 cases where the two components were
      successfully microdissected. Presence of the same mutation in both DCIS and
      invasive components from the same tumor indicates same cellular origin. The role
      of mutant TP53 in the progression of breast cancer is less clear and may vary
      between subtypes.

PMID- 19403345
TI  - Over-activated Notch-1 protects gastric carcinoma BGC-823 cells from TNFalpha
      induced apoptosis.
AB  - BACKGROUND/AIM: The role of Notch-1 in human gastric carcinoma, one of the most
      common carcinomas of the human digestive tract, remains poorly characterised.
      Here, we investigated the effect and mechanism of Notch-1 activation on TNFalpha
      induced apoptosis of human gastric carcinoma BGC-823 cells. METHODS: Cell
      viabililty was measured by MTT assay. Apoptosis was detected by flow cytometry
      assay. Notch-1, Hes-1, caspase-3 p20 and NF-kappaB p65 expressions were assayed
      by Western blotting. NF-kappaB activation was tested by electrophoretic mobility
      shift assay (EMSA), and caspase-3 activation was tested by colorimetric assay.
      RESULTS: BGC-823 cells underwent apoptosis following stimulation with TNFalpha.
      We found that Notch-1 was over-activated by overexpressing exogenous
      intracellular domain of Notch (ICN) via retrovirus-mediated gene transfer, and
      over-activated Notch-1 reduced the TNFalpha-induced growth suppression and
      apoptosis in BGC-823 cells. Down-regulation of Notch-1 by siRNA targeting Notch-1
      enhanced TNFalpha-induced apoptosis in BGC-823 cells. As the molecular mechanism
      involved, we showed over-activated Notch-1 partially suppressed TNFalpha-induced
      activation of caspase-3. However, TNFalpha-induced activation of NF-kappaB was
      not affected by over-activated Notch-1. CONCLUSIONS: Our data indicate that over
      activated Notch-1 significantly protects BGC-823 cells from TNFalpha-induced
      apoptosis, and this effect is mediated, at least in part, by decreasing
      activation of caspase-3 independent of NF-kappaB.

PMID- 19403347
TI  - Investigation of Oddi sphincter structure by optical coherence tomography in
      patients with biliary-type 1 dysfunction: a pilot in vivo study.
AB  - BACKGROUND: Type 1 sphincter of Oddi dysfunction is a clinical entity
      characterised by biliary-type pain, elevated liver biochemical tests, and common
      bile duct dilation. Sphincter fibrosis is a common finding in this type of
      dysfunction and may require in some cases a differential diagnosis with a
      malignant intra-papillary disease. Optical coherence tomography permits high
      resolution, real-time imaging of the sphincter of Oddi microstructure by a probe
      inserted into the common bile duct through an ERCP catheter. No data exist on the
      evaluation of sphincter of Oddi fibrosis by optical coherence tomography during
      ERCP in vivo. OBJECTIVE: To assess the feasibility of optical coherence
      tomography investigation of the sphincter of Oddi structure and assess its
      potential for diagnosing type 1 sphincter of Oddi dysfunction. PATIENTS: Ten
      consecutive patients, five with biliary-type 1 sphincter of Oddi dysfunction and
      five with pancreatic head/mid-body adenocarcinoma not involving the papillary
      region, who underwent both endoscopic ultrasound and therapeutic ERCP, were
      investigated by optical coherence tomography immediately before biliary
      sphincterotomy or stenting. RESULTS: In all sphincter of Oddi dysfunction
      patients optical coherence tomography recognised a hyper-reflective intermediate,
      fibro-muscular layer, significantly thicker than in patients with non
      pathological sphincter of Oddi (p<0.0001). CONCLUSIONS: Optical coherence
      tomography imaging recognised an increased thickness and reflectance of the fibro
      muscular layer of the sphincter of Oddi, very likely determined by fibrosis, and
      was not time-consuming; it can be safely used during ERCP to confirm the
      diagnosis in difficult cases. Its use in clinical practice has one important
      limitation since it requires magnification in the post-procedure computer
      analysis to obtain images useful for diagnosis.

PMID- 19403348
TI  - Genetic polymorphisms in non-alcoholic fatty liver disease: interleukin-6-174G/C
      polymorphism is associated with non-alcoholic steatohepatitis.
AB  - BACKGROUND: Environmental and genetic factors play a role in the pathogenesis and
      natural history of non-alcoholic fatty liver disease (NAFLD). METHODS: In 114
      subjects with NAFLD we report the prevalence and correlation with clinical
      parameters of three polymorphisms: interleukin-6 (-174G/C), plasma cell
      differentiation antigen (K121Q) and microsomal transfer protein (-493G/T). In 59
      biopsied patients with NAFLD the polymorphisms were also related to histological
      features. RESULTS: IL-6 -174C variant was more prevalent (p<0.01) in NAFLD
      compared to controls. In the NAFLD group, C carriers had higher HOMA-IR and
      fasting insulin than G carriers (p<0.05). The prevalence of IL-6/C variant was
      higher (83%) in biopsied than in not biopsied subjects (66%) (p<0.05). In
      biopsied subjects, C carriers had higher HOMA and fasting insulin (p<0.05)
      compared than those with G allele. The prevalence of IL-6 -174G/C polymorphism
      was significantly higher in NASH than in NAFLD (p=0.048). At logistic regression
      analysis IL-6 -174C was an independent predictor of both NAFLD (OR 4.116, C.I.
      1.126-15.048) and NASH (OR 7.035, C.I. 1.167-42.394). Conversely, the
      distribution of PC-1 and MTP polymorphisms was not significantly different
      compared to the control group, nor associated with clinical or histological
      characteristics. CONCLUSIONS: Our data suggest that IL-6 -174C genetic
      polymorphisms, involved in inflammation and insulin resistance, are associated
      with NASH. These data may contribute to the understanding of the genetic
      susceptibility to NAFLD.

PMID- 19403349
TI  - Role of endoscopic ultrasonography in predicting the response to cyclosporin A in
      ulcerative colitis refractory to steroids.
AB  - BACKGROUND AND AIMS: Although cyclosporin A has been reported to be effective in
      the treatment of severe ulcerative colitis, factors predicting its therapeutic
      efficacy remain unclear. Technical progress in endoscopic ultrasonography has
      improved visualisation of the structure of the colon wall. Here, to assess the
      value of endoscopic ultrasonography in predicting the response to cyclosporin A
      treatment, we evaluated the therapeutic effect of cyclosporin A by determining
      the pre- and post-cyclosporin A thickness of the mucosal layer in the rectum
      using endoscopic ultrasonography with an ultrasonic catheter probe. PATIENTS AND
      METHODS: Fifteen ulcerative colitis patients who did not respond to high-doses of
      corticosteroids were treated with cyclosporin A by continuous intravenous
      infusion at 4mg/kg/day for 20 days. Before and 20 days after cyclosporin A
      therapy, clinical disease activity was assessed using clinical activity index
      scores. Colonoscopy and endoscopic ultrasonography were undertaken before and 20
      days after cyclosporin A therapy. RESULTS: Following treatment with cyclosporin
      A, nine patients showed a decrease in clinical activity index score by six points
      or more and were defined as responders, while the other six were defined as non
      responders. Endoscopic ultrasonography measurement using an ultrasonic catheter
      probe showed that thickness of the rectal mucosal layer before cyclosporin A was
      significantly greater in responders than in non-responders (p<0.05). Further,
      thickness after cyclosporin A was statistically decreased (p<0.01) in the
      responders but not in the non-responders. CONCLUSIONS: The ultrasonic catheter
      probe may represent a useful means of predicting and evaluating the efficacy of
      cyclosporin A treatment in severely ill ulcerative colitis patients.

PMID- 19403350
TI  - New insights into liver stem cells.
AB  - Hepatic progenitor cells are bi-potential stem cells residing in human and animal
      livers that are able to differentiate towards the hepatocytic and the
      cholangiocytic lineages. In adult livers, hepatic progenitor cells are quiescent
      stem cells with a low proliferating rate, representing a reserve compartment that
      is activated only when the mature epithelial cells of the liver are continuously
      damaged or inhibited in their replication, or in cases of severe cell loss.
      Hepatic progenitor cell activation has been described in various acute and
      chronic liver diseases. Their niche is composed by numerous cells such as Hepatic
      Stellate Cells, endothelial cells, hepatocytes, cholangiocytes, Kupffer cells,
      pit cells and inflammatory cells. All these cells, numerous hormones and growth
      factors could interact and cross-talk with progenitor cells influencing their
      proliferative and differentiative processes. Hepatic progenitor cells and their
      niche could represent, in the near future, a target for therapeutic approaches to
      liver disease based on cell-specific drug delivery systems. Isolation and
      transplantation of hepatic progenitor cells could represent a new approach for
      therapy of end-stage chronic liver diseases, as they offer many advantages to
      transplantation of mature hepatocytes. The possibility of applying stem cell
      therapy to liver diseases will represent a major goal in this field.

PMID- 19403351
TI  - Development of hyaluronic acid-based scaffolds for brain tissue engineering.
AB  - Three-dimensional biodegradable porous scaffolds play vital roles in tissue
      engineering. In this study, a hyaluronic acid-collagen (HA-Coll) sponge with an
      open porous structure and mechanical behavior comparable to brain tissue was
      developed. HA-Coll scaffolds with different mixing ratios were prepared by a
      freeze-drying technique and crosslinked with water-soluble carbodiimide to
      improve mechanical stability. The pore structure of the samples was evaluated by
      light and scanning electron microscopy, and the mechanical behavior was analyzed
      by mechanical compression and tension testing. The degree of crosslinking was
      determined by the water absorption and trinitrobenzene sulfonic assay, and the HA
      content was determined by a carbazole assay. The results showed that HA-Coll
      scaffolds containing an open porous structure with a homogeneous pore size
      distribution could be fabricated. Certain features of the mechanical properties
      of HA-Coll scaffolds prepared with a Coll:HA mixing ratio of 1:2, and pure HA
      sponges, were comparable with brain tissue. Neural stem cells (NSCs) were
      expanded in number in monolayer culture and then seeded onto the three
      dimensional scaffolds in order to investigate the effects of the different types
      of scaffolds on neurogenic induction of the cells. This study contributes to the
      understanding of the effects of HA content and crosslink treatment on pore
      characteristics, and mechanical behavior essential for the design of HA-Coll
      scaffolds suitable for NSC growth and differentiation for brain tissue
      engineering.

PMID- 19403352
TI  - Basic surgical practice on discarded adipocutaneous flaps in massive weight loss
      surgery.

PMID- 19403353
TI  - A readily available temporary nipple prosthesis to aid positioning of nipple
      areola reconstructions.

PMID- 19403354
TI  - Transabdominal fetal heart rate detection using NIR photopleythysmography:
      instrumentation and clinical results.
AB  - In obstetrics, fetal heart rate (FHR) detection remains the standard for
      intrapartum assessment of fetal well-being. In this paper, a low-power (< 55 mW)
      optical technique is proposed for transabdominal FHR detection using near
      infrared photoplesthysmography (PPG). A beam of IR-LED (890 nm) propagates
      through to the maternal abdomen and fetal tissues, resulting in a mixed signal
      detected by a low-noise detector situated at a distance of 4 cm. Low-noise
      amplification and 24-bit analog-to-digital converter resolution ensure minimum
      effect of quantization noise. After synchronous detection, the mixed signal is
      processed by an adaptive filter to extract the fetal signal, whereas the PPG from
      the mother's index finger is the reference input. A total of 24 datasets were
      acquired from six subjects at 37 +/- 2 gestational weeks. Results show a
      correlation coefficient of 0.96 (p-value < 0.001) between the proposed optical
      and ultrasound FHR, with a maximum error of 4%. Assessment of the effect of probe
      position on detection accuracy indicates that the probe should be close to fetal
      tissues, but not necessarily restricted to head or buttocks.

PMID- 19403355
TI  - Surface current density mapping for identification of gastric slow wave
      propagation.
AB  - The magnetogastrogram (MGG) records clinically relevant parameters of the
      electrical slow wave of the stomach noninvasively. Besides slow wave frequency,
      gastric slow wave propagation velocity is a potentially useful clinical indicator
      of the state of health of gastric tissue, but it is a difficult parameter to
      determine from noninvasive bioelectric or biomagnetic measurements. We present a
      method for computing the surface current density from multichannel MGG recordings
      that allows computation of the propagation velocity of the gastric slow wave. A
      moving dipole source model with hypothetical as well as realistic biomagnetometer
      parameters demonstrates that while a relatively sparse array of magnetometer
      sensors is sufficient to compute a single average propagation velocity, more
      detailed information about spatial variations in propagation velocity requires
      higher density magnetometer arrays. Finally, the method is validated with
      simultaneous MGG and serosal electromyography measurements in a porcine subject.

PMID- 19403356
TI  - Steady-state movement related potentials for brain-computer interfacing.
AB  - An approach for brain-computer interfacing (BCI) by analysis of steady-state
      movement related potentials (ssMRPs) produced during rhythmic finger movements is
      proposed in this paper. The neurological background of ssMRPs is briefly
      reviewed. Averaged ssMRPs represent the development of a lateralized rhythmic
      potential, and the energy of the EEG signals at the finger tapping frequency can
      be used for single-trial ssMRP classification. The proposed ssMRP-based BCI
      approach is tested using the classic Fisher's linear discriminant classifier.
      Moreover, the influence of the current source density transform on the
      performance of BCI system is investigated. The averaged correct classification
      rates (CCRs) as well as averaged information transfer rates (ITRs) for different
      sliding time windows are reported. Reliable single-trial classification rates of
      88%-100% accuracy are achievable at relatively high ITRs. Furthermore, we have
      been able to achieve CCRs of up to 93% in classification of the ssMRPs recorded
      during imagined rhythmic finger movements. The merit of this approach is in the
      application of rhythmic cues for BCI, the relatively simple recording setup, and
      straightforward computations that make the real-time implementations plausible.

PMID- 19403357
TI  - Development and implantation of a minimally invasive wireless subretinal
      neurostimulator.
AB  - A wirelessly operated, minimally invasive retinal prosthesis was developed for
      preclinical chronic implantation studies in Yucatan minipig models. The implant
      conforms to the outer wall of the eye and drives a microfabricated polyimide
      stimulating electrode array with sputtered iridium oxide electrodes. This array
      is implanted in the subretinal space using a specially designed ab externo
      surgical technique that fixes the bulk of the prosthesis to the outer surface of
      the sclera. The implanted device is fabricated on a host polyimide flexible
      circuit. It consists of a 15-channel stimulator chip, secondary power and data
      receiving coils, and discrete power supply components. The completed device is
      encapsulated in poly(dimethylsiloxane) except for the reference/counter electrode
      and the thin electrode array. In vitro testing was performed to verify the
      performance of the system in biological saline using a custom RF transmitter
      circuit and primary coils. Stimulation patterns as well as pulse strength,
      duration, and frequency were programmed wirelessly using custom software and a
      graphical user interface. Wireless operation of the retinal implant has been
      verified both in vitro and in vivo in three pigs for more than seven months, the
      latter by measuring stimulus artifacts on the eye surface using contact lens
      electrodes.

PMID- 19403358
TI  - Estimation of postaverage SNR from evoked responses under nonstationary noise.
AB  - In any measure of event-related potentials, it is important to be able to
      estimate the postaverage signal-to-noise ratio (SNR) in order to assess the
      quality of the measured signals. The estimated postaverage SNR can be an
      important detection criteria (as in infant hearing-screening of evoked auditory
      potentials) and a control factor when comparing signals obtained during different
      conditions (accounting for residual noise variability). Standard SNR estimation
      methods, such as the fixed-single-point (Fsp) statistic (C. Elberling and M. Don,
      "Quality estimation of averaged auditory brainstem responses," Scandinavian
      Audiol., vol. 13, pp. 187-197, 1984), assume a single-stationary noise source,
      with the postaverage SNR increasing proportionally to the number of trials
      averaged. This study proposes a modified version of the Fsp statistic, the
      nonstationary fixed-multiple-point (NS Fmp), that can account for a discrete
      number of noise sources of different power, and can also be modified for weighted
      averaging (WNS Fmp). A new noise segmentation procedure is also proposed that
      dynamically partitions contiguous trials based on their noise power estimates and
      a series of F-tests. Results from computer simulation and real data from auditory
      brain stem recordings show that the NS Fmp method yields lower mean square error
      than do the Fsp, and that the WNS Fmp has higher receiver-operating-curve area
      than do the standard Fsp procedure.

PMID- 19403359
TI  - Micromachined hot-wire thermal conductivity probe for biomedical applications.
AB  - This paper presents the design, fabrication, numerical simulation, and
      experimental validation of a micromachined probe that measures thermal
      conductivity of biological tissues. The probe consists of a pair of resistive
      line heating elements and resistance temperature detector sensors, which were
      fabricated by using planar photolithography on a glass substrate. The numerical
      analysis revealed that the thermal conductivity and diffusivity can be determined
      by the temperature response induced by the uniform heat flux in the heating
      elements. After calibrating the probe using a material (agar gel) of known
      thermal conductivity, the probe was deployed to calculate the thermal
      conductivity of Crisco. The measured value is in agreement with that determined
      by the macro-hot-wire probe method to within 3%. Finally, the micro thermal probe
      was used to investigate the change of thermal conductivity of pig liver before
      and after RF ablation treatment. The results show an increase in thermal
      conductivity of liver after the RF ablation.

PMID- 19403360
TI  - On temporal connectivity of PFC via Gauss-Markov modeling of fNIRS signals.
AB  - Functional near-infrared spectroscopy (fNIRS) is an optical imaging method, which
      monitors the brain activation by measuring the successive changes in the
      concentration of oxy- and deoxyhemoglobin in real time. In this study, we present
      a method to investigate the functional connectivity of prefrontal cortex (PFC)
      Sby applying a Gauss-Markov model to fNIRS signals. The hemodynamic changes on
      PFC during the performance of cognitive paradigm are measured by fNIRS for 17
      healthy adults. The color-word matching Stroop task is performed to activate 16
      different regions of PFC. There are three different types of stimuli in this
      task, which can be listed as incongruent stimulus (IS), congruent stimulus (CS),
      and neutral stimulus (NS), respectively. We introduce a new measure, called
      "information transfer metric" (ITM) for each time sample. The behavior of ITMs
      during IS are significantly different from the ITMs during CS and NS, which is
      consistent with the outcome of the previous research, which concentrated on fNIRS
      signal analysis via color-word matching Stroop task. Our analysis shows that the
      functional connectivity of PFC is highly relevant with the cognitive load, i.e.,
      functional connectivity increases with the increasing cognitive load.

PMID- 19403361
TI  - Neural decoding of finger movements using Skellam-based maximum-likelihood
      decoding.
AB  - We present an optimal method for decoding the activity of primary motor cortex
      (M1) neurons in a nonhuman primate during single finger movements. The method is
      based on the maximum-likelihood (ML) inference, which assuming the probability of
      finger movements is uniform, is equivalent to the maximum a posteriori (MAP)
      inference. Each neuron's activation is first quantified by the change in firing
      rate before and after finger movement. We then estimate the probability density
      function of this activation given finger movement, i.e., Pr(neuronal activation
      (x) | finger movements (m)). Based on the ML criterion, we choose finger
      movements to maximize Pr(x |m). Experimentally, data were collected from 115 task
      related neurons in M1 as the monkey performed flexion and extension of each
      finger and the wrist (12 movements). With as few as 20--25 randomly selected
      neurons, the proposed method decoded single-finger movements with 99% accuracy.
      Since the training and decoding procedures in the proposed method are simple and
      computationally efficient, the method can be extended for real-time
      neuroprosthetic control of a dexterous hand.

PMID- 19403363
TI  - A histogram modification framework and its application for image contrast
      enhancement.
AB  - A general framework based on histogram equalization for image contrast
      enhancement is presented. In this framework, contrast enhancement is posed as an
      optimization problem that minimizes a cost function. Histogram equalization is an
      effective technique for contrast enhancement. However, a conventional histogram
      equalization (HE) usually results in excessive contrast enhancement, which in
      turn gives the processed image an unnatural look and creates visual artifacts. By
      introducing specifically designed penalty terms, the level of contrast
      enhancement can be adjusted; noise robustness, white/black stretching and mean
      brightness preservation may easily be incorporated into the optimization.
      Analytic solutions for some of the important criteria are presented. Finally, a
      low-complexity algorithm for contrast enhancement is presented, and its
      performance is demonstrated against a recently proposed method.

PMID- 19403362
TI  - Three-dimensional imaging of complex neural activation in humans from EEG.
AB  - Electro- or magnetoencephalography (EEG/MEG) are of utmost advantage in studying
      transient neuronal activity and its timing with respect to behavior in the
      working human brain. Direct localization of the neural substrates underlying
      EEG/MEG is commonly achieved by modeling neuronal activity as dipoles. However,
      the success of neural source localization with the dipole model has only been
      demonstrated in relatively simple localization tasks owing to the simplified
      model and its insufficiency in differentiating cortical sources with different
      extents. It would be of great interest to image complex neural activation with
      multiple sources of different cortical extensions directly from EEG/MEG. We have
      investigated this crucial issue by adding additional parameters to the dipole
      model, leading to the multipole model to better represent the extended sources
      confined to the convoluted cortical surface. The localization of multiple
      cortical sources is achieved by using the subspace source localization method
      with the multipole model. Its performance is evaluated with simulated data as
      compared with the dipole model, and further illustrated with the real data
      obtained during visual stimulations in human subjects. The interpretation of the
      localization results is fully supported by our knowledge about their anatomic
      locations and functional magnetic resonance imaging data in the same experimental
      setting. Methods for estimating multiple neuronal sources at cortical areas will
      facilitate our ability to characterize the cortical electrical activity from
      simple, early sensory components to more complex networks, such as in visual,
      motor, and cognitive tasks.

PMID- 19403364
TI  - Variational B-spline level-set: a linear filtering approach for fast deformable
      model evolution.
AB  - In the field of image segmentation, most level-set-based active-contour
      approaches take advantage of a discrete representation of the associated implicit
      function. We present in this paper a different formulation where the implicit
      function is modeled as a continuous parametric function expressed on a B-spline
      basis. Starting from the active-contour energy functional, we show that this
      formulation allows us to compute the solution as a restriction of the variational
      problem on the space spanned by the B-splines. As a consequence, the minimization
      of the functional is directly obtained in terms of the B-spline coefficients. We
      also show that each step of this minimization may be expressed through a
      convolution operation. Because the B-spline functions are separable, this
      convolution may in turn be performed as a sequence of simple 1-D convolutions,
      which yields an efficient algorithm. As a further consequence, each step of the
      level-set evolution may be interpreted as a filtering operation with a B-spline
      kernel. Such filtering induces an intrinsic smoothing in the algorithm, which can
      be controlled explicitly via the degree and the scale of the chosen B-spline
      kernel. We illustrate the behavior of this approach on simulated as well as
      experimental images from various fields.

PMID- 19403365
TI  - Chaos UWB radar for through-the-wall imaging.
AB  - In this paper, we propose to apply a novel chaos-based ultra-wide band (UWB)
      radar for through-the-wall imaging. The proposed chaos modulation offers superior
      resolution compared to conventional UWB radars when applied for through-the-wall
      imaging. A noncoherent receiver is designed based on expectation maximization
      (EM) algorithm. The theoretical detection performance is derived for through-the
      wall detection in the presence and absence of room reverberations as a function
      of dielectric properties of walls, targets, and their geometry illustrating the
      robustness of the proposed modulation against room reverberations. The resolution
      of the proposed modulation is analyzed theoretically and verified through
      simulations for different wall materials. Numerical electromagnetic simulations
      using finite difference time domain (FDTD) method are performed to confirm the
      obtained theoretical results. From the theoretical and simulation analysis, we
      find that the proposed chaos-based pulse amplitude modulated ultra-wide band
      (CPAM-UWB) radar has better detection performance, penetrating ability and
      imaging performance compared to other conventional through-the-wall imaging
      radars.

PMID- 19403366
TI  - Self-similarity driven color demosaicking.
AB  - Demosaicking is the process by which from a matrix of colored pixels measuring
      only one color component per pixel, red, green, or blue, one can infer a whole
      color information at each pixel. This inference requires a deep understanding of
      the interaction between colors, and the involvement of image local geometry.
      Although quite successful in making such inferences with very small relative
      error, state-of-the-art demosaicking methods fail when the local geometry cannot
      be inferred from the neighboring pixels. In such a case, which occurs when thin
      structures or fine periodic patterns were present in the original, state-of-the
      art methods can create disturbing artifacts, known as zipper effect, blur, and
      color spots. The aim of this paper is to show that these artifacts can be avoided
      by involving the image self-similarity to infer missing colors. Detailed
      experiments show that a satisfactory solution can be found, even for the most
      critical cases. Extensive comparisons with state-of-the-art algorithms will be
      performed on two different classic image databases.

PMID- 19403367
TI  - Extraproximal method application for a Stackelberg-Nash equilibrium calculation
      in static hierarchical games.
AB  - A regularized version of the extraproximal method is suggested for finding the
      Stackelberg-Nash equilibrium in a multiparticipant static game. There exist two
      levels of hierarchy in decision making: The first one consists of a leader
      decision, and the second one is formed by the decisions of the (N - 1) followers.
      The followers react to the leader's announced strategy by playing according to
      the Nash equilibrium concept, selecting among themselves that whose equilibrium
      is most favorable or unfavorable for the leader. Here, applying the extraproximal
      technique, the Stackelberg-Nash equilibrium is attained. The convergence of the
      suggested procedure is analyzed. Simulation results illustrate the feasibility of
      this method.

PMID- 19403368
TI  - Indexing 3-D human motion repositories for content-based retrieval.
AB  - Content-based retrieval of the similar motions for the human joints has
      significant impact in the fields of physical medicine, biomedicine,
      rehabilitation, and motion therapy. In this paper, we propose an efficient
      indexing approach for 3-D human motion capture data, supporting queries involving
      both subbody motions as well as whole-body motions.

PMID- 19403369
TI  - Novel lossless FMRI image compression based on motion compensation and customized
      entropy coding.
AB  - We recently proposed a method for lossless compression of 4-D medical images
      based on the advanced video coding standard (H.264/AVC). In this paper, we
      present two major contributions that enhance our previous work for compression of
      functional MRI (fMRI) data: 1) a new multiframe motion compensation process that
      employs 4-D search, variable-size block matching, and bidirectional prediction;
      and 2) a new context-based adaptive binary arithmetic coder designed for lossless
      compression of the residual and motion vector data. We validate our method on
      real fMRI sequences of various resolutions and compare the performance to two
      state-of-the-art methods: 4D-JPEG2000 and H.264/AVC. Quantitative results
      demonstrate that our proposed technique significantly outperforms current state
      of the art with an average compression ratio improvement of 13%.

PMID- 19403370
TI  - An embedded mobile ECG reasoning system for elderly patients.
AB  - With the increase in the number senior citizens and chronic diseases, the number
      of elderly patients who need constant assistance has increased. One key point of
      all critical care for elderly patient is the continuous monitoring of their vital
      signs. Among these, the ECG signal is used for noninvasive diagnosis of
      cardiovascular diseases. Also, there is a pressing need to have a proper system
      in place for patient identification. Errors in patient identification, and hence
      improper administration of medication can lead to disastrous results. This paper
      proposes a novel embedded mobile ECG reasoning system that integrates ECG signal
      reasoning and RF identification together to monitor an elderly patient. As a
      result, our proposed method has a good accuracy in heart beat recognition, and
      enables continuous monitoring and identification of the elderly patient when
      alone. Moreover, in order to examine and validate our proposed system, we propose
      a managerial research model to test whether it can be implemented in a medical
      organization. The results prove that the mobility, usability, and performance of
      our proposed system have impacts on the user's attitude, and there is a
      significant positive relation between the user's attitude and the intent to use
      our proposed system.

PMID- 19403371
TI  - Almost sure exponential stability of recurrent neural networks with Markovian
      switching.
AB  - This paper presents new stability results for recurrent neural networks with
      Markovian switching. First, algebraic criteria for the almost sure exponential
      stability of recurrent neural networks with Markovian switching and without time
      delays are derived. The results show that the almost sure exponential stability
      of such a neural network does not require the stability of the neural network at
      every individual parametric configuration. Next, both delay-dependent and delay
      independent criteria for the almost sure exponential stability of recurrent
      neural networks with time-varying delays and Markovian-switching parameters are
      derived by means of a generalized stochastic Halanay inequality. The results
      herein include existing ones for recurrent neural networks without Markovian
      switching as special cases. Finally, simulation results in three numerical
      examples are discussed to illustrate the theoretical results.

PMID- 19403372
TI  - [Establishment of a colorectal cancer cell line with PRL-3 and CDH22 gene knock
      down by lentivirus-mediated RNA interference].
AB  - OBJECTIVE: To establish a colorectal cancer cell line with stable PRL-3 and CDH22
      gene knock-down for investigating the role of PRL-3 and CDH22 genes in the
      carcinogenesis and metastasis of colorectal cancer. METHODS: A recombinant
      lentiviral vector targeting CDH22 gene was obtained using the pENTRTM/U6
      construct and pLenti6/BLOCK-iT (TM)-DEST vector. The recombinant lentivirus was
      harvested from 293FT cells cotransfected with the optimized ViraPower(TM)
      Packaging Mix and the pLenti6/BLOCK-iT(TM)-DEST expression construct. SW480/PRL-3
      cells were infected with the recombinant lentivirus targeting CDH22, and SW480
      cells with stable PRL-3 and CDH22 knock-down were screened by blasticidin
      selection. PRL-3 expression in the cells was determined by real-time RT-PCR.
      RESULTS The titer of the lentivirus for the second infection was 8 x 10(5) U/ml.
      Seventeen positive clones were selected, among which the Clone 1 exhibited
      substantially down-regulated CDH22 and PRL-3 mRNA expressions. CONCLUSIONS: A
      human colorectal cancer cell line with stable PRL-3 and CDH22 gene knock-down has
      been established.

PMID- 19403373
TI  - [Protective effect of leptin against cerebral ischemia/reperfusion injury in
      mice].
AB  - OBJECTIVE: To investigate the protective effect of leptin against cerebral
      ischemia/reperfusion injury in mice. METHODS: Mouse models of transient focal
      cerebral ischemia were established by occlusion of the right middle cerebral
      artery for 2 h followed by 24 h reperfusion. The infarct volume and neurological
      deficit scores following leptin treatment were determined using TTC staining and
      the Longa's score, respectively, to evaluate the protective effect of leptin
      against ischemic cerebral injury. The levels of lactate dehydrogenase (LDH),
      malondialdehyde (MDA) and nitric oxide (NO) in the brain tissue were measured by
      colorimetry. The histopathological changes in the brain were observed with HE
      staining, and the expression of glial fibrillary acidicprotein (GFAP) was
      detected by immunohistochemistry. RESULTS: Leptin treatment markedly reduced
      cerebral infarct volume and neurological deficits induced by transient ischemia.
      The LDH, MDA and NO levels in the brain tissues were significantly decreased
      after leptin treatment, which also alleviated the histopathological injury,
      maintained the normal morphology of the astrocytes and increased the expression
      of GFAP. CONCLUSION: Leptin produces obvious protective effect against cerebral
      ischemia/reperfusion injury by inhibiting lipid peroxidation, stabilizing the
      internal environment and adjusting the activity of the astrocytes.

PMID- 19403374
TI  - [Spontaneous differentiation of human embryonic stem cells into hematopoietic
      cells].
AB  - OBJECTIVE: To characterize the time course of spontaneous differentiation of in
      vitro cultured human embryonic stem cells (hESCs) into hematopoietic cells to
      provide experimental evidence for induction of hematopoietic commitment of hESCs.
      METHODS: In human embryoid bodies (hEBs) derived from spontaneous differentiation
      of chESC3, a hESC cell line we established previously, the expressions of such
      genes as KDR, Bmi1, Scl and gata2 were detected by RT-PCR every other day during
      the 12-day differentiation to monitor the process of the hematopoiesis. The
      hematopoietic stem cell marker CD34 was examined using flow cytometry to evaluate
      the efficiency of hematopoietic differentiation of the cells on days 6, 8, 10 and
      12. The spontaneously differentiated hESCs were seeded in the hematopoietic
      colony culture system to study the hematopoietic colony forming ability.
      Immunocytochemical staining for CD45 was performed on the hEBs to examine the
      emergence of mature hematopoietic cells. RESULTS: The expressions of the
      hematopoietic stem cell-related genes KDR and Bmi-1 were detected in the hESCs,
      and on days 4 to 6, the two genes were upregulated with prolonged cuture of the
      hEBs. Scl and gata2 gene expressions were detected since 6-8 days of culture and
      maintained high expressions till day 12. Flow cytometry revealed a gradual
      increase in CD34-positive cells in the culture, with positivity rates on days 6,
      8, 10, and 12 of (1.4-/+0.4)%, (3.4-/+1.3)%, (5.5-/+2.2)%, and (5.1-/+1.7)%,
      respectively. The numbers of CD43-positive cell colonies on days 6, 8, 10, and 12
      were 0, 7-/+2, 37-/+11, and 89-/+29 in each 10(5) cells, respectively.
      Immunocytochemical staining identified CD45-positive cells on days 10, 12, 15,
      and 18 in the cell colonies, with the positive cell numbers of 0, 40.5-/+15.09,
      178.6-/+55.89, and 253.0-/+52.04, respectively. CONCLUSION: The hESCs undergo
      spontaneous hematopoietic differentiation in 3 stages, including the
      differentiation into germ layer-specific cells (days 6-8), expansion period of
      the hematopoitic progenitors (days 8-12), and maturation of the hematopoietic
      cells (after day 15).

PMID- 19403375
TI  - [Experimental study of human adipocyte dedifferentiation for adipose tissue
      engineering].
AB  - OBJECTIVE: To investigate the dedifferentiation of mature adipocytes and the
      possibility of adipose tissue engineering using dedifferentiated adipocytes.
      METHODS: Human adipose tissue was harvested from healthy women undergoing
      abdominal liposuction procedures, and mature adipocytes were isolated with
      enzymatic digestion and cultured by ceiling adherent culture method, using the
      third-passage cells for subsequent experiment. The cells were cultured in
      adipogenic, chondrogenic or osteogenic media, and Oil red-O staining, Alcian blue
      staining and Alizarin red staining were used for dedifferentiation
      identification. The third-passage cells labeled with DiI were mixed with fibrin
      glue and injected subcutaneously on one side of the nude mouse back (n=6), and
      fibrin glue solution without cells as control was injected on the other side
      (n=6). After 8 weeks of cell implantation, the specimens were harvested for
      general observation and histological, Oil red-O staining and fluorescent
      microscope analyses. RESULTS: Mature adipocytes were round, unilocular cells.
      After ceiling adherent culture, the adipocytes underwent morphological changes
      into fibroblast-like cells indicating their dedifferentiation. The
      dedifferentiated adipocytes were induced for adipogenic, chondrogenic and
      osteogenic differentiation in specified media. Eight weeks after the cell
      injection in nude mice, newly formed tissue occurred which was identified as
      mature adipose tissue. The implants without cells were completely absorbed in the
      control group. CONCLUSION: Mature adipocytes can dedifferentiate in vitro
      culture, and the dedifferentiated adipocytes are capable of differentiating into
      adipogenic, chondrogenic and osteogenic lineages. Adipose tissue engineering can
      be achieved in vivo using the dedifferentiated adipocytes as the seed cells.

PMID- 19403376
TI  - [Effect of rAAV-mediated RNA interference against EB virus-encoded latent
      membrane protein 1 on nasopharyngeal carcinoma cell proliferation and metastasis
      in nude mice].
AB  - OBJECTIVE: To study the role of Epstein-Barr virus (EBV)-encoded latent membrane
      protein 1 (LMP-1) in nasopharyngeal carcinoma (NPC) cell growth and metastasis in
      vivo by recombinant adeno-associated virus (rAAV)-mediated RNA interference
      (RNAi). METHODS: Specific small hairpin RNA (shRNA) targeting EBV-LMP-1 gene was
      designed and synthesized to construct two rAAV vectors rAAV-shRNA-LMP-1 and rAAV
      EGFP. The multiplicity of infection (MOI) was confirmed using different titers of
      rAAV-EGFP to transfect the NPC cell line C666-1. The C666-1 cells were
      transfected by rAAV-shRNA-LMP-1 at the optimal MOI titer and the inhibition
      efficiency of the target gene expression was determined with RT-PCR. The C666-1
      cells with RNAi of LMP-1 gene were injected into nude mouse liver via laparotomy
      to establish the animal model of hepatic and lung metastases of NPC cells. The
      metastases of the C666-1 cells in the liver and lungs were observed to assess the
      effect of LMP-1 gene silencing on the tumorigenic and metastatic potentials of
      the cells in vivo. RESULTS: The transfection efficiency of 5 x 10(4) virus
      genome/cell rAAV-EGFP exceeded 95%. The expression of the target gene was
      suppressed by over 90% as shown by RT-PCR after transfection with rAAV-shRNA-LMP
      1 at 5 x 10(4) virus genome/cell. Animal experiments showed that compared with
      rAAV-EGFP, rAAV-shRNA-LMP-1 transfection did not reduce the primary tumor volume
      implanted into the liver, but significantly inhibited the intrahepatic and lung
      metastases of the NPC cells. CONCLUSION: LMP-1 expression can be suppressed
      effectively by rAAV-mediated RNAi, and LMP-1 suppression does not obviously
      affect the tumor cell growth but can inhibit their metastasis in vivo.

PMID- 19403377
TI  - [Construction of a eukaryotic expression vector of the gene encoding rat
      interferon-gamma-inducible protein and its expression in NIH 3T3 cells].
AB  - OBJECTIVE: To construct an expression vector of the gene encoding rat interferon
      gamma-inducible protein (IP-10) and identify its expression in NIH 3T3 cells.
      METHODS: IP-10 gene was amplified by polymerase chain reaction (PCR) and inserted
      into the eukaryotic expression vector pcDNA3.1(+). After identification by PCR,
      restriction endonuclease digestion and sequence analysis, the recombinant
      expression vector pcDNA3.1(+)-IP-10 was transfected into NIH 3T3 cells via
      liposome. Immunofluorescence method was used to confirm the expression of
      pcDNA3.1(+)-IP-10 in the transfected NIH 3T3 cells. The expression of IP-10
      protein in the supernatant of the transfected cells was examined by Western
      blotting. RESULTS: PCR, restriction endonuclease digestion and sequence analyses
      confirmed successful construction of the recombinant vector pcDNA3.1(+)-IP-10.
      Immunofluorescence assay identified the expression of pcDNA3.1(+)-IP-10 in NIH
      3T3 cells, and the expression of IP-10 protein was detected by Western blotting
      in the supernatant of the transfected cells. CONCLUSION: A eukaryotic expression
      vector pcDNA3.1(+)-IP-10 has been successfully constructed, which provides the
      basis for investigating the therapeutic effect of IP-10 on Th1 type autoimmune
      disease.

PMID- 19403378
TI  - [Vasoactive intestinal peptide enhances angiogenesis after focal cerebral
      ischemia].
AB  - OBJECTIVE: To investigate the effect of vasoactive intestinal peptide (VIP) on
      angiogenesis after focal cerebral ischemia. METHODS: Focal cerebral ischemia was
      induced by middle cerebral artery occlusion (MCAO) for 120 min in adult SD rats
      with intracerebroventricular VIP administration at the beginning of reperfusion.
      Immunohistochemistry was performed to assay BrdU immunoreactive endothelial
      cells, expressions of VEGF, flt-1 and flk-1 in the ischemic zone, and the protein
      expressions of vascular endothelial growth factor (VEGF) in the brain was
      measured using Western blotting. RESULTS: Immunohistochemical staining revealed
      significantly increased BrdU immunoreactive endothelial cells on the margins of
      the ischemic lesion in rats treated with VIP as compared with that in the control
      rats (P<0.05). VIP significantly increased the number of VEGF immunoreactive
      cells and flt-1- and flk-1-positive endothelial cells in comparison with the
      control group (P<0.01). Western blotting showed that VIP treatment resulted in
      significantly increased VEGF protein level in the ipsilateral hemisphere
      (P<0.05). CONCLUSIONS: VIP enhances angiogenesis in the ischemic brain by
      increasing the expressions of VEGF in the brain tissue and its receptors flt-1
      and flk-1 in the endothelial cells.

PMID- 19403379
TI  - [Expression of extracellular signal-regulated protein kinases in the subcutaneous
      fascia of rats and their changes after acupuncture].
AB  - OBJECTIVE: To observe the effect of acupuncture on the expression of
      extracellular signal-regulated protein kinases 1/2 (ERK1/2) in the subcutaneous
      fascia of SD rats. METHODS: Eighteen SD rats were randomly divided into 6 groups
      (n=3) including 5 acupuncture groups and a control group. The rats in the 5
      acupuncture groups received electro-acupuncture therapy in the regions of the
      inguinal groove, and at 0, 1, 6, 12, and 36 h after the last therapy, the
      superfacial fascia surrounding the acupuncture point (about 1.5 cm in diameter)
      were collected. The fascia tissues at the corresponding sites and at the acupoint
      Zusanli (ST36) were obtained from the control rats. The expression of ERK1/2 and
      phosphorylated ERK1/2 (p-ERK1/2) in the tissues were detected by Western
      blotting. RESULTS: ERK1/2 and p-ERK1/2 expressions were detected in the tissues
      harvested from both the acupoint and the non-acupoint in the control rats with
      similar expression intensities. In the rats of each acupuncture group, ERK1/2
      expression was significantly increased on the acupuncture side in comparison with
      the control side. CONCLUSION: The normal loose connective tissue may participate
      in tissue proliferation and differentiation possibly via phosphorylation of ERK.
      Acupuncture can promote the signal transduction pathway of ERK, which can be a
      possible mechanism for the effect of acupuncture in modulating the
      physiopathological conditions.

PMID- 19403380
TI  - [A simple and efficient method for establishing a mouse model of orthotopic MB49
      bladder cancer].
AB  - OBJECTIVE: To establish a simple and efficient method for establishing a mouse
      model of orthotopic superficial bladder cancer. METHODS: C57BL/6 mice were
      anesthetized with sodium pentobarbital and catheterized with modified IV catheter
      (24 G). The mice were intravesically pretreated with HCl and then with NaOH, and
      after washing the bladders with phosphate-buffered saline (PBS), 100 microl (1 x
      10(7)) MB49 cells were infused and allowed to incubate in the bladder for 2 h
      followed intravesical mitomycin C (MMC) administration. The tumor formation rate,
      survival, gross hematuria, and bladder weight were determined as the outcome
      variables, and the pathology of the bladders was observed. RESULTS: Instillation
      of MB49 tumor cells resulted in a tumor formation rates of 100% in all the
      pretreated groups while 0% in the control group without pretreatment. MMC
      significantly reduced the bladder weight as compared to PBS. CONCLUSION: We have
      successfully established a stable, reproducible, and reliable orthotopic bladder
      cancer model in mice.

PMID- 19403381
TI  - [Molecular cloning of a novel human testis-specific gene TDRG1].
AB  - OBJECTIVE: To clone a novel human testis-specific gene TDRG1. METHODS: A new
      contig of expression sequence tags (ESTs) Hs.180197 was identified from the
      testis libraries using digital differential display (DDD) to screen the novel
      human testis-specific gene. To validate the use of bioinformatics approaches in
      gene discovery, the ESTs Hs.180197, which was predicted to be testis specific,
      was chosen for further study. Reverse transcriptase-polymerase chain reaction (RT
      PCR) was performed on different normal tissues to identify the expression of
      Hs.180197 in human testis. Using bioinformatics methods and IMAGE cloning of this
      contig, the full-length cDNA sequence of the noval human gene was cloned.
      RESULTS: This novel gene was 1197 bp in length, located in chromosome 6p21.1
      p21.2. The sequence of the open reading frame was 504-806 bp, as confirmed by RT
      PCR and sequencing in human testis. The cDNA encodes a novel protein of 100 amino
      acids with a theoretical molecular weight of 10 000 and isoelectric point of
      6.81. The sequence shares no significant homology with any known protein in the
      databases. Semi-quantitative RT-PCR analysis of multiple tissues further showed
      that the novel gene was expressed specifically in adult human testis. Considering
      a possible relation of this novel gene with the function of human testis, we
      named this new gene TDRG1 (testis development related gene 1, GenBank accession
      number: DQ168992). CONCLUSION: DDD combined with laboratory validation is an
      efficient method for identifying new human functional genes.

PMID- 19403382
TI  - [Effect of sinomenine on the expression of chemokines and chemokine receptors in
      dendritic cells from patients with rheumatoid arthritis].
AB  - To investigate the effect of sinomenine on the expression of chemokines and
      chemokine receptors of dendritic cells in patients with rheumatoid arthritis in
      vitro. METHODS: The peripheral blood mononuclear cells isolated from 8 patients
      with rheumatoid arthritis were induced to differentiate into dendritic cells with
      GM-CSF and IL-4. The dendritic cells were exposed to sinomenine at high (5
      mmol/L), moderate (2 mmol/L), and low (1 mmol/L) concentrations or treated with
      the control medium. The expression of CCR5 and CCR7 on the surface of the
      dendritic cells were measured by flow cytometry, and the CCR5 and CCR7 mRNA
      expressions were detected by semi-quantitative PCR. Enzyme-linked immunosorbent
      assay (ELISA) was used to measure the expressions of CXCL9 (MIG), CXCL10 (IP-10)
      and CXCL11 (ITAC). RESULTS: Compared with the control cells, the dendritic cells
      treated with sinomenine, especially at high and moderate concentrations, showed
      significantly lowered mRNA and protein expressions of CCR5 and CCR7. Similar
      results were observed in the expressions of CXCL9 (MIG) and CXCL10 (IP-10), but
      not in CXCL11 (ITAC). CONCLUSION: Sinomenine produces therapeutic effect on
      rheumatoid arthritis possibly by inhibiting the expression of chemokines and
      chemokine receptors in the dendritic cells to suppress the chemotactic migration
      of the dendritic cells.

PMID- 19403383
TI  - [Biocompatibility between human adipose-derived mesenchymal stem cells and
      porcine bone scaffolds].
AB  - OBJECTIVE: To study the compatibility between human adipose-derived mesenchymal
      stem cells and porcine bone scaffolds. METHODS: Porcine bone tissues were co
      cultured with adipose-derived mesenchymal stem cells, and the complex was
      observed under scanning electron microscope. The viability and alkaline
      phosphatase (ALP) activity of the cells were examined with the cells co-cultured
      with human bone scaffold as the control. RESULTS: At 4 and 10 days after the co
      culture, the adipose-derived mesenchymal stem cells were observed to extend
      pseudopodia to adhere to the two scaffold materials. MTT assay showed that the
      cell proliferation on both of the materials increased with time, and the two cell
      complexes exhibited similar pattern of changes in ALP activity. CONCLUSION: As
      the seed cells, human adipose-derived mesenchymal stem cells exhibit good
      comparability with porcine bone scaffold, suggesting their potential of
      constructing tissue-engineered bone graft.

PMID- 19403384
TI  - [Expressions of metastatic tumor antigen 1 and hypoxia-inducible-factor l alpha
      in lung cancer and their clinical significance].
AB  - OBJECTIVE: To explore the correlation of the expressions of metastatic tumor
      antigen 1 (MTA1) and hypoxia-inducible-factor l alpha (HIF-1alpha) to the
      clinical features of lung cancer. METHODS: The expressions of MTA1 and HIF-1alpha
      proteins in 59 lung cancer patients were detected by immunohistochemistry.
      RESULTS: Positive staining of MTA1 and HIF-1alpha was found in 54.24% and 50.85%
      of the patients, respectively. MTA1 expression was not found to correlated to any
      of the clinical parameters. HIF-1alpha expression was significantly lower in
      poorly differentiated than in moderately and well differentiated lung cancer
      (P<0.05), and a positive association between the expressions of MTA1 and HIF
      17alpha were noted (P<0.05). CONCLUSION: MTA1 and HIF-1alpha overexpression
      occurs in lung cancer possibly as an important factor of lung carcinogenesis.
      MTA1 may promote lung carcinogenesis by enhancing HIF-1alpha protein activity.

PMID- 19403385
TI  - [Screening and preliminary analysis of the apoptosis- and proliferation-related
      genes in nasopharyngeal carcinoma].
AB  - To screen and analyze the apoptosis- and proliferation-related genes in human
      nasopharyngeal carcinoma (NPC). METHODS: According to gene ontology
      classification, the abnormal expressions of the genes related to cell apoptosis
      and proliferation were identified in the NPC gene chip data. The cell apoptosis-
      and proliferation-related genes expressed in each of the 3 stages, as defined by
      the tree model for the pathogenesis and progression of NPC, were screened, and
      with literature review, their distribution in the tree model were analyzed.
      RESULTS: Nineteen genes related to cell apoptosis were found in NPC, among which
      9 were down-regulated (such as DNASE1L3) and located in the chromosome deletion
      regions, and 10 were up-regulated (such as DEDD) in the chromosome amplification
      regions. Twenty-one cell proliferation-related genes were identified, including 8
      down-regulated genes (such as TUSC2) in the chromosome deletion regions and 13 up
      regulated ones (such as EMP1) in the chromosome amplification regions. In the
      chromosome deletion regions, the down-regulated cell apoptosis-related genes
      participated mostly in inducing and regulating cell apoptosis, and the up
      regulated cell proliferation-related genes in the chromosome amplification
      regions were mostly associated with the positive regulation of cell
      proliferation. CONCLUSION: NPC occurs possibly through two pathways by inhibiting
      cell apoptosis or by promoting excessive cell proliferation.

PMID- 19403386
TI  - [Preparation and identification of monoclonal antibody against enoyl-CoA
      hydratase 1].
AB  - OBJECTIVE: To prepare monoclonal antibodies (mAbs) against enoyl-CoA hydratase 1
      (ECH1). METHODS: Normal human liver tissues were homogenized, and the
      mitochondria were isolated by differential centrifugation. The total
      mitochondrial proteins were used to immunize BALB/c mice to prepare mAbs by
      routine hybridoma technique. The mAbs were characterized by ELISA, Western
      blotting and immunohistochemistry. The specificity of the antibody was identified
      by mass spectrometry (MS) following immunoprecipitation (IP) and confirmed by Uni
      ZAP expression library screening. RESULTS: One clone of the hybridoma BGB095
      secreting specific mAb against ECH1 was obtained. The mAb was identified to
      belong to Ig subclass IgG1 and could be used in ELISA, Western blotting,
      immunohistochemistry, and immunoprecipitation. CONCLUSION: A hybridoma cell line
      stably secreting specific mAb against ECH1 has been established. The specific mAb
      against ECH1 can be of great value for functional and distribution studies of
      ECH1.

PMID- 19403387
TI  - [Construction of a bait plasmid containing human telomerase RNA mutant in yeast
      three-hybrid system].
AB  - OBJECTIVE: To construct a bait plasmid containing human telomerase RNA with
      multiple point mutations in a yeast three-hybrid system and evaluate the toxicity
      of the recombinant bait plasmid. METHODS: The primers were designed according to
      the hTR sequence and the target mutation sites for inducing T-->A mutations at
      the 41st, the 80th and 102nd nucleotides of the hTR gene using the overlapping
      extension PCR (OE-PCR) method. The mutant was cloned into PMD18T vector,
      confirmed by sequencing, sub-cloned into the bait plasmid PRH3' and identified
      with PCR and restriction enzyme digestion. The recombinant bait plasmid was then
      transformed into yeast L40 ura3/pHyblex/ZeoMS2 for toxicity test. RESULTS:
      Sequence analysis demonstrated successful introduction of point mutations at the
      target sites without causing random mutation. The recombined bait plasmid
      constructed showed no obvious toxicity against the host yeast cells. CONCLUSIONS:
      The recombinant plasmid containing the human telomerase RNA mutant (PRH3'-hTRm)
      has been successfully constructed and can be used as the bait plasmid in yeast
      three-hybrid system.

PMID- 19403388
TI  - [Adaptive super resolution algorithm for under-sampled images].
AB  - OBJECTIVE: A new algorithm of adaptive super-resolution (SR) reconstruction based
      on the regularization parameter is proposed to reconstruct a high-resolution (HR)
      image from the low-resolution (LR) image sequence, which takes into full account
      the inaccurate estimates of motion error, point spread function (PSF) and the
      additive Gaussian noise in the LR image sequence. We established a novel
      nonlinear adaptive regularization function and analyzed experimentally its
      convexity to obtain the adaptive step size. This novel algorithm can effectively
      improve the spatial resolution of the image and the rate of convergence, which is
      verified by the experiment on optical images.

PMID- 19403389
TI  - [Necrotic cells induce and promote inflammatory responses in vitro].
AB  - OBJECTIVE: To investigate the effect of necrotic cells on the secretion of
      inflammatory cytokines. METHODS: RAW264.7 macrophages and necrotic mouse
      thymocytes induced by heating were incubated for 18 h at a ratio of 5:1 in the
      absence or presence of lipopolysaccharide (LPS, 100 ng/ml). The supernatant of
      the cell culture was collected and the expression and secretion of the pro
      inflammatory cytokines were measured using Bio-Plex suspension system. RESULTS:
      The secretions of tumor necrosis factor-alpha (TNF-alpha) and interlukine-6 (IL
      6) by macrophages co-cultured with the necrotic cells were significantly enhanced
      as compared with the control cells. The necrotic cells also significantly
      augmented the secretion of the pro-inflammatory cytokines induced by LPS.
      CONCLUSION: Necrotic cells not only induces pro-inflammatory cytokine expression
      by themselves but also work synergistically with LPS to enhance the cytokine
      production, suggesting the important roles of necrotic cells to initiate and
      maintain the inflammatory responses.

PMID- 19403390
TI  - [Effects of leptin on RAAS and nitric oxide production in isolated rat
      glomeruli].
AB  - OBJECTIVE: To investigate the changes in angiotensinogen (AGT), angiotensin II
      type 1 receptor (AT(1)R), endothelial nitric oxide synthase (eNOS) mRNA and
      protein expressions and nitric oxide (NO) content in the rat glomeruli in
      response to leptin stimulation. METHODS: The glomeruli isolated from male SD rats
      were stimulated with 3 nmol/L leptin for 2 h. Real-time PCR and Western blotting
      were performed to analyze the mRNA and protein expressions of AGT, AT(1)R and
      eNOS in the glomeruli, and nitrite concentration in the glomeruli was measured by
      nitrate reductase assay. RESULTS: In comparison with the control group, exposure
      to leptin increased the mRNA levels of AGT, ATR(1) and eNOS in the isolated
      glomeruli by 2.69-/+0.17, 3.77-/+0.16 and 2.56-/+0.29 folds (P=0.024, 0.018 and
      0.044), and their protein levels by 2.06-/+0.10, 2.67-/+0.08 and 1.61-/+0.13
      folds (P=0.021, 0.015 and 0.032), respectively. The NO production in the
      glomeruli was also increased by 2.77-/+0.14 folds (P=0.000) following leptin
      exposure. CONCLUSION: Leptin exposure of isolated rat glomeruli directly causes
      activation of the internal renal renin-angiotensin system and enhanced NO
      production, suggesting that leptin plays a role in the pathogenesis of
      maladaptation in renal hemodynamics in obesity.

PMID- 19403391
TI  - [Clinical features of interstitial pneumonitis due to interferon alpha therapy
      for chronic hepatitis C].
AB  - OBJECTIVE: To analyze the clinical features of interstitial pneumonitis (IP)
      associated with interferon therapy for chronic hepatitis C. METHODS: We report
      the first case of IP in China resulting from pegylated interferon alpha-2a in
      combination with ribavirin for treatment of hepatitis C viral infection. A
      statistical analysis of the related literatures documenting such IP cases was
      performed using SPSS 11.5 software. RESULTS: Of the 22 patients reported to
      develop IP after interferon therapy alone or in combination with ribavirin, 83%,
      72% and 56% of the patients had the symptoms of dyspnoea, dry cough and fever,
      respectively. Twenty of these cases presented with restrictive pulmonary
      functional impairment and/or hypoxemia, and diffuse infiltration on chest
      radiography and/or CT. Complications were documented in 71% of the cases within
      12 weeks of the treatment. The majority (85%) of the patients had favorable
      prognoses with an average recovery time of 7.5 weeks. Compared with the patients
      with mild and moderate pulmonary function impairment, 8 patients with severe
      pulmonary functional impairment had early onset of IP during the interferon
      therapy (6.6 vs 14.1 weeks, P<0.05), and a higher rate of corticosteroid
      treatment (75% vs 54%, P>0.05). CONCLUSION: IP is a rare pulmonary complication
      associated with IFN therapy, and patients with chronic hepatitis C should be
      followed up closely in the first 12 weeks of interferon therapy. Prompt
      discontinuation of medication is mandatory in the presence of IP, and
      corticosteroid therapy may not be essential for patients with mild or moderate
      pulmonary functional impairment under close monitoring. The severity of pulmonary
      damage is associated with the time of complication occurrence, and
      corticosteroids are required when obvious pulmonary toxicity occurs in early
      stage of the treatment (within 6 weeks) to reduce the pulmonary damage.

PMID- 19403393
TI  - [Effect of Shuanghuanglian injection on cerebral nuclear factor-kappaB expression
      in mice with viral encephalitis].
AB  - OBJECTIVE: To observe the effect of Shuanghuanglian injection on cerebral
      expression of nuclear factor-kappaB (NF-kappaB) in mice with viral encephalitis.
      METHODS: The mice with experimental viral encephalitis received treatment with
      Shuanghuanglian injection at the dose of 0.2, 1.5, and 5 for 5, 10 or 20
      consecutive days. The total RNA of the brain tissue was extracted to analyze the
      protein and mRNA expression of NF-kappaB using Western blotting and RT-PCR,
      respectively. RESULTS: Compared with the control group, the mice with
      experimental viral encephalitis showed significantly increased protein and mRNA
      expressions of NF-kappaB (P<0.01). Treatment with Shuanghuanglian injection at
      the doses of 0.2 and 1.5 mg/kg significantly lowered NF-kappaB protein and mRNA
      expressions in the brain of mice with viral encephalitis (P<0.05), and the effect
      was even more obvious at the dose of 5 mg/kg (P<0.01). CONCLUSION:
      Shuanghuanglian injection can reduce the expression of NF-kappaB in the brain of
      mice with viral encephalitis in a dose- and time-dependent manner.

PMID- 19403392
TI  - [Effect of bone morphogenic protein 7 on nephrin expression and distribution in
      diabetic rat kidneys].
AB  - OBJECTIVE: To evaluate the effect of bone morphogenic protein 7 (BMP-7) on
      nephrin expression and distribution in diabetic rat kidneys. METHODS: Twenty rats
      with diabetes mellitus (DM) induced by streptozotocin (STZ) injection were
      randomly divided into DM model group and BMP-7 treatment group, with another 10
      normal rats serving as the normal control group. The rats in BMP-7 group received
      intraperitoneal human recombinant BMP-7 injections at 30 microg/kg twice a week
      for 24 consecutive weeks, while normal saline was administered in rats of the
      other two groups. Blood glucose and 24 hour urinary protein and creatinine (Ccr)
      were measured at 8, 16 and 24 weeks, and the rats were sacrificed at 24 weeks to
      obtain the renal tissues for detecting the expression and distribution of nephrin
      using immunofluorescence assay and RT-PCR and for examining the expressions of
      transforming growth factor-beta1 (TGF-beta1) and WT1 using immunohistochemistry.
      RESULTS: Compared with the normal control group, the DM model group showed
      significantly increased 24 hour urinary protein, kidney to body weight ratio and
      TGF-beta1 expression, but had lowered Ccr, glomerular podocyte number and nephrin
      expression. The linear distribution of nephrin along the capillary loops as found
      in the normal control group became granular in the kidney of diabetic rats. The
      rats in BMP-7 group showed less urinary protein excretion, lower TGF-beta1
      expression and greater glomerular podocyte number than those in the DM group, and
      the expression and distribution of nephrin remained normal in the kidney.
      CONCLUSION: Administration of BMP-7 can significantly suppress the down
      regulation of nephrin expression and maintain its normal distribution in the
      podocytes in diabetic rats possibly in association with a direct suppression of
      TGF-betasignaling.

PMID- 19403394
TI  - [Induced differentiation of rat adipose-derived stem cells into Schwann-like
      cells].
AB  - OBJECTIVE: To assess the differentiation potential of rat adipose-derived stem
      cells (ADSCs) into Schwann-like cells in vitro. METHODS: ADSCs isolated from
      adult SD rats were cultured in vitro and identified with the cell surface
      antigens CD44, CD49d and CD106 by immunocytochemistry. The ADSCs of the sixth to
      eighth passages were inoculated in polylysine-coated culture plate and cultured
      for 12 days in DMEM/F12 culture medium containing 10% fetal bovine serum, 5 ng/ml
      platelet-derived growth factor, 10 ng/ml basic fibroblast growth factor, 14
      micromol/L Forskolin and 200 ng/ml Heregulin to induce their differentiation in
      vitro. Immunocytochemistry was performed to identify the expression of the cell
      surface markers nestin, glial fibrillary acidic protein (GFAP), S-100, and P75.
      RESULTS: The isolated and purified ADSCs were positive for CD44 and CD49d
      expressions but negative for CD106. After 12 days of culture in the conditional
      culture medium, most of the cells showed positive expressions of GFAP, S-100, and
      P75, the specific protein markers of Schwann cells. CONCLUSION: Adult rat ADSCs
      are confirmed to have potentials of neuroglial differentiation and capable of
      differentiating into Schwann-like cells in vitro.

PMID- 19403395
TI  - [Expression of ZNF217 in human ovarian cystadenocarcinoma and its clinical
      significance].
AB  - OBJECTIVE: To explore the correlation of ZNF217 expression to the carcinogenesis
      and progression of human ovarian cancer. METHODS: Immunohistochemistry and real
      time RT-PCR were used to detect ZNF217 expression in human ovarian
      cystadenocarcinoma, ovarian cystadenoma and normal ovary tissues. RESULTS: The
      expression levels of ZNF217 protein and mRNA in ovarian cystadenocarcinoma was
      significantly higher than those in matched ovarian cystadenoma and normal tissues
      (P<0.05). No significant difference was found in the expression between ovarian
      cystadenoma and normal ovarian tissues (P>0.05). The mRNA expression in the
      specimens was consistent with the protein expression of ZNF217 (P<0.05).
      CONCLUSION: ZNF217 gene expression is closely correlated to the occurrence and
      clinical stages of ovarian carcinomas, suggesting that ZNF217 can be an important
      candidate gene responsible for the occurrence and progression of ovarian
      carcinomas.

PMID- 19403396
TI  - [PPAR gamma agonist rosiglitazone alleviates hypoxia/reoxygenation-induced
      oxidative stress and apoptosis in rat cardiac myocytes].
AB  - OBJECTIVE: To observe the effects of different concentrations of PPAR gamma
      agonist rosiglitazone on hypoxia/reoxygenation-induced oxidative stress, cell
      viability and apoptosis in rat cardiac myocytes. METHODS: Cultured rat cardiac
      myocytes were divided into 5 groups, namely group I (normal group), group II (20
      micromo/L ROS group), group III (I/R group), group IV (I/R+20 micromo/L ROS
      group), and group V (I/R+80 micromo/L ROS group). Group IV and group V were
      treated with rosiglitazone 12 h before hypoxia/reoxygenation. The changes in cell
      morphology were observed under optical and transmission electron microscopy, and
      levels of malondialdehyde (MDA), superoxide dismutase (SOD) activity, and lactate
      dehydrogenase (LDH) content were determined after the treatment. MTT assay was
      performed to assess the cell viability and flow cytometry was used to analyze the
      cell apoptosis. RESULTS: Hypoxia/reoxygenation resulted in significantly
      increased MDA and LDH contents and apoptosis of the cardiac myocytes (P<0.05),
      but lowered SOD activity and the cell viability (P<0.05). The MDA and LDH
      contents and apoptotic rate were significantly lower but SOD content and cell
      vitality significantly higher in groups IV and V than in group III (P<0.05).
      Group V showed significantly lower MDA and LDH contents and apoptotic rate but
      higher but SOD content and cell vitality than group IV (P<0.05). Electron
      microscopy revealed obvious apoptotic changes in group III, and only mild changes
      were found in group V. CONCLUSION: Rosiglitazone can significantly reduce
      hypoxia/reoxygenation-induced oxidative stress in cardiac myocytes, improve the
      cell viability and dose-dependently reduce the apoptotic rate of the cardiac
      myocytes.

PMID- 19403397
TI  - [Effect of leukotriene receptor antagonist on cough variant asthma].
AB  - OBJECTIVE: To study the curative effect of leukotriene receptor antagonist on
      cough variant asthma (CVA). METHODS: Sixty-four CVA patients received treatment
      with bricany and montelukas and 68 control patients had bricany treatment for 4
      weeks. The recurrence rate was observed in the two groups during the follow-up
      for 6 months. RESULTS: The remission time of two groups were 2.5-/+3.6 and 5.3
      /+3.8 days in acute phase, respectively, showing a significant difference between
      them (P<0.05). The recurrence rate of the two groups within 6 months were 20.09%
      and 40.87%, respectively, showing also significantly differences (P<0.05).
      CONCLUSION: Leukotriene receptor antagonist and bricany can effectively control
      CVA and significantly lower the short-term recurrence rate of CVA.

PMID- 19403398
TI  - [Effect of alexandrite laser treatment for hair removal in Tibet mini-pigs].
AB  - OBJECTIVE: To observe the histological and ultrastructural changes of the skin
      and hair follicles following hair removal by alexandrite laser in Tibet mini
      pigs. METHODS: Twelve healthy Tibet mini-pigs with dark hair were treated with
      alexandrite laser for hair removal. The skin specimens were taken immediately and
      at 1 h and 1, 3, 5, 10, 15, 30, 60 days after the laser treatment for observation
      under optical and transmission electron microscope. RESULTS: Laser hair removal
      resulted in extensive coagulation necrosis, carbonization and falling of the
      subcutaneous hair shafts, and some of the cells in the outer root sheath and hair
      bulb underwent degenerative and necrotic changes. One hour after laser treatment,
      the cells in the outer root sheath and bulb exhibited nuclear condensation,
      fragmentation and or karyolysis characteristic of cell apoptosis. The cell
      apoptosis reached the peak level on day 3 after the laser exposure, accompanied
      by endothelial degeneration in the hair papilla vessels, edema and lymphocyte
      infiltration in the dermal tissues. Tissue reaction and inflammation were
      relieved on day 5, and the dermal tissue and follicles recovered their normal
      structures on day 10. At 60 days after the treatment, the hair follicles
      decreased markedly but the structure of the residue follicles remained normal.
      CONCLUSION: Alexandrite laser exposure results in selective destruction of the
      follicles by inducing direct coagulation and cell apoptosis to achieve permanent
      hair removal. Tibet mini-pigs with black hair can be used as the animal model of
      clinical laser hair removal.

PMID- 19403399
TI  - [Effects of Liuweidihuang Decoction on cell proliferation and melanin synthesis
      of cultured human melanocytes in vitro].
AB  - OBJECTIVE: To investigate the effects of Liuweidihuang Decoction on the
      proliferation and melanin synthesis of cultured human melanocytes in vitro.
      METHODS: MTT assay was used to assess the proliferation of cultured human
      melanocytes after treatment with Liuweidihuang Decoction, and NaOH assay was
      employed to determine melanin synthesis. RESULTS: Liuweidihuang Decoction at the
      concentration of 5%-15% did not affect the proliferation of the melanocytes
      (P>0.05), and the decoction at 20%-30% significantly inhibited the cell
      proliferation, especially at the optimal concentration of 30% (P<0.01). The
      decoction promoted melanin synthesis in the melanocytes at the concentration of
      10%-15% with the optimal concentration of 15% (P<0.01) but failed to produce such
      an effect at 20%-30%. CONCLUSION: Liuweidihuang Decoction exert a two-way
      regulation on the proliferation and melanin synthesis of cultured human
      melanocytes in vitro.

PMID- 19403400
TI  - [Effects of sustained-release alpha-lipoic acid tablet on blood lipid, blood
      sugar and insulin in hyperlipidemic New Zealand rabbits].
AB  - OBJECTIVE: To evaluate the effect of sustained-release alpha-lipoic acid tablets
      (SRLA) on blood lipid, glucose and insulin levels in hyperlipidemic New Zealand
      rabbits. METHODS: Twenty-four New Zealand rabbits were randomized into normal
      diet group, high-fat diet group, and high-fat diet + SRLA (300 mg/tablet) group
      with corresponding feed. At the beginning and 4 weeks after the feeding, the
      serum levels of total cholesterol (TC), triglycerides (TG), high-density
      lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C),
      blood glucose, and serum insulin were measured, and insulin sensitivity index
      (ISI) was calculated. RESULTS: Four weeks after feeding with high-fat diet, the
      insulin levels was elevated and the ISI lowered in the New Zealand rabbits,
      indicating successful establishment of the animal model of hyperlipidemia.
      Compared with the high-fat diet group, the serum levels of TG, TC, LDL-C and
      insulin were significantly reduced (P<0.05), and the ISI was significantly
      increased (P<0.05) in high fat diet + SRLA group. But no statistically
      significant difference was found in the blood glucose among the 3 groups.
      CONCLUSION: SRLA can significantly correct blood lipid and insulin disorders in
      hyperlipidemic New Zealand rabbits and prevent the occurrence of insulin
      resistance and hyperlipidemia.

PMID- 19403401
TI  - [Gene cloning, prokaryotic expression and functional evaluation of intimin from
      enterohemorrhagic Escherichia coli O157:H7].
AB  - OBJECTIVE: To obtain highly purified intimin encoded by the eae gene and study
      its adhesion activity. METHODS: The eae gene was amplified from enterohemorrhagic
      Escherichia coli O157:H7 (EHEC) chromosome by PCR and cloned into pMD19-T vector.
      The eae gene was cut from pMD19-T vector and subcloned into the prokaryotic
      expression plasmid pET28a(+), and expressed in E.coli BL21(DE3). The recombinant
      protein was purified with Ni(2+)-chelating affinity chromatography followed by
      identification with SDS-PAGE and Western blotting. The purified intimin was
      detected by immunofluorescence staining to test its adhesion. RESULTS: The 2805
      bp eae gene fragment was obtained, and the recombinant expression plasmid
      pET28a(+)-eae was successfully expressed in E.coli BL21 (DE3). The molecular
      weight of the recombinant protein was 97 000. Purified recombinant intimin was
      recognized by rabbit anti-O157 antiserum, and bound to the surface of HEp-2 cells
      as revealed by immunofluorescence staining. CONCLUSION: Highly purified and
      immunoreactive intimin has been successfully obtained, which can adhere to the
      surface of HEp-2 cells. The acquisition of recombinant intimin provides the basis
      for studying its interaction with the host receptors during EHEC O157:H7
      infection.

PMID- 19403402
TI  - [Bone marrow stem cell mobilization to the peripheral blood and tumor necrosis
      factor-alpha expression in ischemic myocardium in rabbit models of hibernating
      myocardium].
AB  - OBJECTIVE: To investigate the changes in peripheral blood bone marrow stem cells
      and tumor necrosis factor-alpha gene expression in the ischemic myocardium in
      rabbit models of hibernating myocardium. METHODS: Twenty-four male Japanese white
      rabbits were randomized into 4 groups, including a sham-operated group and 3
      model groups with hibernating myocardium induced by partial ligation of the left
      anterior descending coronary artery. The percentage of CD34-positive cells in the
      peripheral blood was evaluated by flow cytometry, and TNF-alpha mRNA expression
      in the ischemic myocardium was determined by real-time RT-PCR in the 3 model
      groups (at 3, 7, or 28 days after the operation) and in the sham-operated group.
      RESULTS: In rabbits with partial ligation of the left anterior descending
      coronary artery, the percentage of CD34-positive cells in the peripheral blood
      and myocardial TNF-alpha mRNA expression were significantly increased at 3 and 7
      days after the operation in comparison with those in the sham-operated group and
      those at 28 days postoperatively (P<0.01). No significant differences were found
      in the percentage of CD34 positive cells or myocardial TNF-alpha mRNA expression
      between the sham-operated group and the rabbits 28 days after the coronary artery
      ligation (P>0.05). CONCLUSION: Bone marrow stem cell can be mobilized into the
      peripheral blood in rabbit hibernating myocardium model possibly by increasing
      TNF-alpha gene expression in the ischemic myocardium.

PMID- 19403403
TI  - [Effect of X-ray exposure on soluble tumor necrosis factor receptor-p75 release
      in hepatocellular carcinoma HepG2 cells in vitro].
AB  - OBJECTIVE: To investigate the effects of X-ray exposure on the release of soluble
      tumor necrosis factor receptor-p75 (sTNFR-p75) in hepatocellular carcinoma HepG2
      cells in vitro. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to
      examine the levels of sTNFR-p75 in the supernatants of HepG2 cells before and
      after X-ray exposure. The cell apoptosis was analyzed by flow cytometry and
      transmission electron microscope(TEM), and the morphological changes of the cells
      were examined under optical microscope and transmission electron microscope(TEM).
      RESULTS: X-ray exposure of the cells resulted in a strong increase of cell
      apoptosis (P<0.05) and sTNFR-p75 production in the cells as compared with the
      those before the exposure (P<0.01). Optical microscopy revealed apoptotic changes
      of HepG2 cell after the exposure, shown as cell shrinkage, spherical cell
      morphology, cytoplasmic and nuclear condensation. Apoptotic bodies were detected
      by TEM. CONCLUSION: X-ray exposure induces HepG2 cells apoptosis by inhibiting
      the release of sTNFR-p75 into the supernatant.

PMID- 19403404
TI  - [Contrast-enhanced ultrasound findings of breast cancer].
AB  - OBJECTIVE: To study the manifestation of breast cancers of different sizes in
      contrast-enhanced sonography. METHODS: Eighty-four patients with breast cancers
      were examined by contrast-enhanced ultrasound. Among them, the tumor diameter was
      beyond 2.0 cm in 50 cases, and no greater than 2.0 cm in the rest cases. The time
      intensity curve (TIC) on the enhanced images was analyzed quantitatively, and the
      relations between the type of TIC and the enhancement patterns of the tumors were
      analyzed. RESULTS: The enhancement patterns of the breast cancers showed
      significant difference between patients with tumor diameter beyond 2.0 cm and
      those with smaller tumors (P<0.01), but the other parameters were comparable
      between the two groups (P>0.05). CONCLUSION: The enhancement patterns of breast
      cancers differ between tumors with sizes over 2.0 cm and smaller tumors, and
      differential analysis is suggested in the diagnosis of breast cancer using
      contrast-enhanced ultrasound.

PMID- 19403405
TI  - [Construction of point mutation plasmids expressing HCV NS3/4A with different
      secondary structures at amino-terminal and their expressions in Huh 7 cells].
AB  - OBJECTIVE: To construct point mutation plasmids expressing HCV NS3/4A with
      different secondary structures at amino-terminal, and express the constructs in
      Huh 7 cells. METHODS: Using pSG5/M-H05-5/4A as the template (A1-1) and primers
      designed according to the typing criteria, 4 single point mutation plasmids,
      namely pSG5/M-H05-5(A1-2)/4A(A1-2) (Y56F), pSG5/M-H05-5(B1-1)/4A(B1-1) (L80Q),
      pSG5/M-H05-5(B2-1)/4A(B2-1) (V51A), and pSG5/M-H05-5(B2-2)/4A(B2-2) (S61A), were
      constructed. With A1-2, B2-1, and B2-2 as the templates, the leucine to glutamine
      mutation at position 80 (L80Q) was induced to construct another 3 double point
      mutation plasmids pSG5/M-H05-5(B1-2)/4A(B1-2), pSG5/M-H05-5(A2-1)/4A(A2-1), and
      pSG5/M-H05-5(A2-2)/4A(A2-2), respectively. DNA sequencing was performed for
      confirmation of the mutations. Huh 7 cells were transfected with the constructs
      using FuGene 6 transfection reagents. Indirect immunofluorescence staining and
      Western blotting were used to detect the expression of the constructs. RESULTS:
      Indirect immunofluorescence assay revealed 4 subcellular localization patterns of
      NS3 protein, including dot-like staining, diffuse staining, doughnut-like
      staining, and rod-shape staining. Western blotting also demonstrated successful
      expression of the constructs and weak in cis and in trans NS3 serine protease
      activities of subtypes A2-1 and B2-1 in comparison with other subtypes.
      CONCLUSION: The point mutation plasmids expressing HCV NS3/4A with different
      secondary structures at amino-terminal are constructed successfully, which
      provides the basis for further study of different subtypes of HCV.

PMID- 19403406
TI  - [Respiratory syncytial virus infection promotes the production of thymic stromal
      lymphopoietin and accelerates Th2 inflammation in mouse airway].
AB  - OBJECTIVE: To investigate the effect of respiratory syncytial virus (RSV)
      infection on the production of thymic stromal lymphopoietin (TSLP) and Th1/Th2
      balance in asthmatic mice. METHODS: Thirty-two female BALB/c mice were randomly
      divided into 4 groups, namely the PBS group, ovalbumin (OVA) group, RSV group and
      OVA/RSV group. The mice were sensitized by OVA and then stimulated with nebulized
      OVA, and RSV was inoculated into the nasal cavity of the mice. BUXCO noninvasive
      lung function detection was performed to examine the airway response to
      metacholine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the
      serum levels of IL-4, IL-5, IL-13, and IFN-gamma in the mice. The cells in the
      bronchoalveolar lavage fluid (BALF) were counted and classified, and the
      supernatants of the BALF were used for the detection of TSLP. Histopathological
      changes in the lung tissues of the mice were examined using HE staining, and
      immunohistochemistry using anti-mouse TSLP antibody was performed to examine TSLP
      expressions in the airway epithelial cells. RESULTS: RSV infection promoted the
      production of TSLP in the asthmatic mice, and the concentration of TSLP in
      OVA/RSV group (2.13-/+0.05 ng/ml) was significantly higher than that in the other
      groups (P<0.01). RSV infection increased the serum levels of IL-4, IL-5, IL-13,
      and IFN-gamma in the mice. The total BALF cells, eosinophils, lymphocytes and
      neutrophils in OVA/RSV group were significantly higher than those in the other
      groups; noninvasive lung function examination showed higher Penh value in OVA/RSV
      group (318.66-/+50.87) than in the other groups when the inhaled metacholine
      increased to 6.25 mg/ml (P<0.01). More obvious and extensive airway inflammatory
      cell infiltration in OVA/RSV group were observed, and immunohistochemical
      staining also showed higher expression of TSLP in the airway epithelial cells of
      OVA/RSV group. CONCLUSIONS: RSV infection promotes the production of TSLP in the
      airway epithelial cells and increases the level of Th2 cytokines in asthmatic
      mice. Concurrent RSV infection can exacerbate Th2 inflammatory reaction in
      asthmatic mice.

PMID- 19403407
TI  - [Determination of the concentrations of interleukin-18 and other cytokines in the
      synovial fluid in patients with osteoarthritis].
AB  - OBJECTIVE: To determine the concentrations of interleukin-18 (IL-18), IL-6, IL-8,
      and prostaglandin E2 (PGE2) in the synovial fluid in patients with osteoarthritis
      (OA), and explore the role of IL-18 in the pathogenesis of OA. METHODS: The
      synovial fluid was collected from 30 patients with knee OA, and the
      concentrations of IL-18 and the other cytokines were measured using enzyme-linked
      immunosorbent assay (ELISA). A linear regression was performed between IL-18 and
      the other cytokines. RESULTS: The average IL-18 and PGE2 concentrations were 220
      /+304 pg/ml and 89-/+104 pg/ml in the synovial fluid, respectively, and the two
      cytokines showed a positive correlation in the synovial fluid (r=0.628, P=0.001).
      The IL-18 concentration was also correlated to the concentrations of IL-6 (1200
      /+1587 pg/ml, n=22; r=0.590, P=0.008) and IL-8 (5190-/+6024 pg/ml, n=9; r=0.776,
      P=0.014). CONCLUSION: IL-18 can promote PGE2 production, which causes cartilage
      degradation in OA, thus therapies targeting this cytokine may prove an effective
      approach to early OA treatment.

PMID- 19403408
TI  - [Effect of angiotensin1-7 on alpha-smooth muscle actin protein expression in rat
      hepatic stellate cells].
AB  - OBJECTIVE: To investigate the effect of angiotensin II and angiotensin1-7 on
      alpha-smooth muscle actin (alpha-SMA)-induced Ca(2+)-independent pathways
      mediated by Rho kinase2 in hepatic stellate cells (HSCs). METHODS: HSC-T6 cells
      were treated with 10 micromol/L of AngII, Ang1-7, AngII +Ang1-7, and Ang1-7+A779.
      RT-PCR was used to detect the expression of Rho kinase2 (Rock2) in Ca(2+)
      independent pathways, and alpha-SMA protein expression was detected by Western
      blotting. RESULTS: The mRNA expression of Rock2 increased significantly in the
      cells after AngII treatment (P<0.01), but decreased following Ang1-7 treatment.
      Ang1-7 treatment significantly reduced alpha-SMA level in AngII-induced cells
      (P<0.01). CONCLUSION: Ang1-7 can inhibit AngII-induced activation of Rock2 and
      reduce alpha-SMA expression in HSCs.

PMID- 19403409
TI  - [Alterations of peripheral blood endothelial progenitor cells from patients with
      ST elevation myocardial infarction after snake venom fibrinolytic enzyme
      therapy].
AB  - OBJECTIVE: To investigate the morphological and quantitative alterations of
      peripheral blood endothelial progenitor cells (EPCs) in patients with ST
      elevation myocardial infarction (STEMI) after snake venom fibrinolytic enzyme
      therapy. METHODS: Sixty patients with STEMI and 20 control patients free of STEMI
      were enrolled in this study. The mononuclear cells were isolated from the
      peripheral blood of the STEMI patients before and 3 and 7 days after fibrinolytic
      enzyme injection. The isolated cells were cultured in RPMI1640 medium
      supplemented with vascular endothelial growth factor 165 (VEGF165) and basic
      fibroblast growth factor (bFGF). The EPCs were characterized as adherent cells of
      positive for both DiL-acLDL and FITC-UEA-I by direct fluorescent staining. The
      cell morphology was observed and the number of the colony-forming units (CFU) was
      determined by phase-contrast microscope. RESULTS: The number of the EPCs
      increased obviously in patients with STEMI 3 days after fibrinolytic enzyme
      injection, and reduced 7 days after the injection but remained greater than that
      in the control group. The injection of fibrinolytic enzyme did not result obvious
      changes in the number of CFU in the patients with STEMI. CONCLUSION: Snake venom
      fibrinolytic enzyme injection can increase the peripheral blood EPCs in patients
      with STEMI.

PMID- 19403410
TI  - [Recombinant adenovirus-mediated expression of 1.2-copy hepatitis B virus DNA in
      three hepatocytes].
AB  - OBJECTIVE: To study hepatitis B virus (HBV) expression in 3 hepatocytes infected
      with recombinant adenovirus containing 1.2-copy HBV DNA.a METHODS: A chicken
      hepatoma cell line and two human hepatocytes were infected by the recombinant
      adenovirus containing 1.2-copy HBV DNA at 25 pfu/cell. HBV-specific mRNA was
      detected by RT-PCR 3 days after the infection, and HBsAg and HBeAg were detected
      by ELISA and HBV DNA by real-time PCR daily after the infection. RESULTS: HBV
      mRNA expression was detected in all the 3 cells after recombinant adenovirus
      infection, and the quantities of HBV DNA and HBV antigens in the culture
      supernatant increased with the passage of time.a CONCLUSION: Infection with the
      recombinant adenovirus containing 1.2-copy HBV DNA can mediate HBV infection in
      the 3 cells in vitro.

PMID- 19403411
TI  - [Relationship between preeclampsia umbilical blood flow and perinatal outcomes].
AB  - OBJECTIVE: To study the relationship between preeclampsia umbilical blood flow
      changes and the pregnancy outcomes. METHOD: The umbilical arterial blood flow
      parameters including the S/D, pulsatility index (PI), resistance index (RI) and
      the average birth weight, Apgar score and placental weight changes were analyzed
      in 106 preeclampsia patients (including 43 mild and 63 severe cases), with 89
      women with normal pregnancy as the control. The relation between the blood flow
      parameters and the perinatal outcomes were analyzed. RESULTS: S/D, PI, and RI all
      tended to increase with the severity of preeclampsia, and these indices were
      significantly higher in patients with severe preeclampsia than in the control
      group (P<0.01) but showed no significant differences between mild preeclampsia
      group and the control group (P>0.05). The average birth weight of the newborns,
      Apgar scores, and placental weight were significantly lower (P<0.01), and the
      incidence of fetal growth restriction (FGR) and perinatal mortality significantly
      higher in severe preeclampsia group than in the control group (P<0.01). No
      significant differences were found in these parameters between the mild
      preeclampsia and the control groups (P>0.05). CONCLUSIONS: Umbilical artery blood
      flow parameters as indicators for determining the fetal status can be used to
      predict the pregnancy outcomes.

PMID- 19403412
TI  - [Three-dimensional reconstruction technique in gastrocnemius flap surgery:
      initial clinical application].
AB  - OBJECTIVE: To discuss the experience with three-dimensional reconstruction
      technique in initial clinical application in gastrocnemius muscle flap surgery.
      METHOD: From 2007 to 2008, 7 patients received gastrocnemius muscle flap
      surgeries to repair the wounds. Preoperative CT angiography or magnetic resonance
      imaging (MRI) was performed after injection of the contrast media for
      individualized three-dimensional gastrocnemius muscle flap reconstruction using
      Amira4.1 software. According to the size of the defect in the wound,
      individualized three-dimensional gastrocnemius muscle flap was designed and
      harvested from the posterior leg. RESULTS: Individualized three-dimensional
      reconstruction of the gastrocnemius flap was performed in 7 cases, and the
      reconstructed flaps clearly displayed the blood vessels, skin and the adjacent
      three-dimensional structures. In 6 cases the main perforating branched and trunk
      of the blood vessels in the designed flap were consistent with the surgical
      findings; in 1 case, the perforating branches failed to be clearly displayed in
      the designed flap, and surgical examination identified perforating branches with
      an average diameter of 0.5 mm (minimally 0.3 mm). The flaps survived in all the 7
      cases. CONCLUSIONS: Three-dimensional reconstruction of the gastrocnemius flap
      based on the lower limb CT angiography or MRI allows three-dimensional
      observation of the anatomy of the flap and accurate marking of the extent of the
      flap to be harvested, therefore avoiding intraoperative injuries to the blood
      vessels to better survival of the flaps.

PMID- 19403413
TI  - [Detection of miR-122a and miR-224 expression in hepatocellular carcinoma by real
      time fluorescence quantitative RT-PCR].
AB  - OBJECTIVE: To detect the expressions of miR-122 and miR-224 in hepatocellular
      carcinoma (HCC) by real-time fluorescence quantitative RT-PCR and investigate the
      significance of miRNAs in early diagnosis of HCC. METHOD: 2(-Delta Delta CT)
      method was used for quantitative analysis of the expression pattern of miR-122
      and miR-224 in 35 HCC and adjacent normal tissues. All the quantitative results
      were confirmed by Northern blotting. RESULTS: Compared with adjacent normal
      tissues, the HCC tissues showed significant miR-122 down-regulation (P<0.01) and
      miR-224 over-expression (P<0.001). CONCLUSIONS: HCC has obvious alteration in the
      expression patterns of miR-122 and miR-224, and real-time fluorescence
      quantitative RT-PCR provide a new means for early, efficient, and accurate
      diagnosis of HCC.

PMID- 19403414
TI  - [Application of laparoscopic surgery following neoadjuvant chemoradiotherapy for
      mid-low rectal cancer].
AB  - OBJECTIVE: To evaluate the safety and feasibility of laparoscopic surgery
      following neoadjuvant chemoradiotherapy (CRT) for mid-low rectal cancer. METHOD:
      A retrospective analysis was conducted among 24 patients with mid-low rectal
      cancer who received laparoscopic total mesorectal excision (TME) after
      neoadjuvant CRT. Another 24 patients with mid-low rectal cancer were randomly
      selected form those undergoing primary laparoscopic TME to serve as the control
      group. The clinical data and surgical data of the two groups of patients were
      collected and analyzed comparatively. RESULTS: TME after CRT resulted in
      significantly lower lymph node yield compared with the control group (7.08-/+6.5
      vs 12.5-/+4.1, P<0.05). The two groups were comparable in the operative time,
      intraoperative blood loss, intestinal function recovery, positive surgical
      margins, rate of conversion to open surgery, and occurrence of intra- and
      postoperative complications. CONCLUSIONS: Laparoscopic surgery of mid-low rectal
      cancer after neoadjuvant CRT can be safe and feasible and produce surgical
      effects comparable to exclusive laparoscopic surgery.

PMID- 19403415
TI  - [Small interference RNA targeting nuclear factor-kappaB inhibits endometriotic
      angiogenesis in chick embryo chorioallantocic membrane].
AB  - OBJECTIVE: To investigate the effect of small interference RNA (siRNA) targeting
      nuclear factor-kappaB (NF-kappaB) on endometriosis. METHOD: The eutopic
      endometrium of women with endometriosis were transplanted into the nonvascular
      region of 8-day-old chicken embryo chorioallantocic membrane (CAM), and the
      effects of NF-kappaB p65 siRNA on the vascularization and endometriotic lesion
      formation were tested with proper controls. RESULTS: Transplantation of the
      endometrium onto the CAM resulted in a strong angiogenic response in the chicken
      tissue. The angiogenesis was significantly reduced and endometriotic lesion
      formation significantly suppressed with siRNA targeting NF-kappaB in comparison
      with the control group. CONCLUSIONS: The NF-kappaB pathway is involved in the
      development of endometriotic lesions in vitro, and NF-kappaB gene silencing
      reduces endometriotic angiogenesis and promotes cell apoptosis in the
      endometriotic lesions, suggesting that NF-kappaB might be a good target for
      endometriosis treatment.

PMID- 19403416
TI  - [Dynamic contrast-enhanced CT patterns and pathologies of noncalcified pulmonary
      tuberculomas].
AB  - OBJECTIVE: To analyze characteristic CT enhancement patterns of noncalcified
      pulmonary tuberculomas and their pathological basis. METHOD: Fifty-six patients
      with noncalcified pulmonary tuberculomas underwent surgical resection of the
      tuberculomas. Enhanced CT images of these tuberculomas were reviewed and analyzed
      in relation to the histological findings. RESULTS: Of the 56 patients, 45 showed
      no enhancement in the tuberculomas, which were histologically characterized by
      central caseous necrosis and a poorly vascularized peripheral fibrotic zone.
      Eleven patients showed ring-like or eggshell enhancement, and the central low
      density region was histologically confirmed to be caused by caseous or liquefied
      necrosis, while the ring enhancement resulted pathologically from moderately or
      well vascularized peripheral fibrotic or granulomatous tissues. CONCLUSIONS:
      Pulmonary tuberculomas consists mainly of caseous necrotic tissues characterized
      by no enhancement and ring or eggshell enhancement on dynamic contrast-enhanced
      CT.

PMID- 19403417
TI  - [Tbx3 upregulation may be one of the malignant biomarkers of breast cancer].
AB  - OBJECTIVE: To explore the role of abnormal Tbx3 expression in the pathogenesis of
      breast cancer. METHOD: The total RNA of 4 breast cancer cell lines and 5 normal
      breast samples was extracted by routine Trizol method. After reverse
      transcription of the total RNA into cDNA, Tbx3 mRNA expression was detected in
      these samples by real-time PCR. Immunohistochemistry was used to examine the
      differences in Tbx3 protein expression between 60 breast cancer samples and 34
      normal breast tissue samples. RESULTS: Compared to normal breast tissue samples,
      the breast cancer cell lines showed markedly increased Tbx3 mRNA expression. The
      results of immunohistochemistry demonstrated a significant upregulation of Tbx3
      protein expression in the 60 breast cancer tissues in comparison with the normal
      breast tissues, as was consistent with Tbx3 mRNA expressions in these tissue
      samples. CONCLUSIONS: The mRNA and protein expressions of Tbx3 are markedly
      upregulated in breast cancer cell lines and tissue samples, suggesting that Tbx3
      may serve as one of the malignant biomarkers in the pathogenesis of breast
      cancer.

PMID- 19403418
TI  - [Effects of hyperbilirubinemia on distortion product otoacoustic emission,
      auditory brainstem response and mismatch negativity in guinea pigs].
AB  - OBJECTIVE: To explore the characteristics of distortion product otoacoustic
      emission (DPOAE), auditory brainstem response (ABR) and mismatch negativity (MMN)
      in guinea pigs with hyperbilirubinemia and assess the impact of
      hyperbilirubinemia on their hearing functions. METHOD: Normal neonatal guinea
      pigs were randomly divided into normal control, low- and high-dose bilirubin
      groups. DPOAE, ABR and MMN were tested and compared between the 3 groups of
      guinea pigs. RESULTS: The DPOAE was comparable between the 3 groups (P>0.05). The
      guinea pigs with peritoneal injection of low-dose bilirubin exhibited
      significantly prolonged wave III and V latencies and I-III interwave intervals
      during the ABR test in comparison with the control group (P<0.05). All the ABR
      parameters were significantly different between the high-dose bilirubin group and
      the control group (P<0.05). The detection rates of MMN were significantly
      different between the 3 groups (Chi(2)=7.438, P=0.024), and the average MMN
      latency was significantly shorter in the control group than in the high-dose
      group (P<0.05), but the amplitudes of MMN remained similar between the 3 groups
      (P>0.05). CONCLUSIONS: Hyperbilirubinemia results impairment primarily of
      retrocochlear auditory pathway with relative mild damage of the cochlear. Apart
      from sensorineural auditory impairment, hyperbilirubinemia may also cause central
      auditory processing abnormalities.

PMID- 19403419
TI  - [Diagnosis of liver pathologies based on apparent diffusion coefficient of
      magnetic resonance diffusion-weighted imaging in a rabbit model of liver
      fibrosis].
AB  - OBJECTIVE: To assess the value of apparent diffusion coefficient (ADC) of
      magnetic resonance diffusion-weighted imaging (MR-DWI) for diagnosis of the liver
      pathologies in rabbit model of liver fibrosis. METHOD: MR-DWI with four different
      b values (200, 500, 300 and 600 s/mm(2)) was performed in 4 normal New Zealand
      white rabbits and 13 rabbits with experimental liver fibrosis. For each rabbit, 4
      ADC values were obtained in the left and right lobes of the liver. According to
      the ISHAK criteria of liver histopathological scoring and fibrosis staging
      system, all the liver specimens were histopathologically graded (scores 1-6 for
      grade I, 7-12 for grade II, and 13-18 for grade III) and assessed for fibrosis
      staging (stages I to VI). The variation of ADC values were analyzed based on the
      results of histopathological grading and fibrosis staging. RESULTS: The 4 ADC
      values were obviously lower in rabbits with liver fibrosis than in the normal
      control rabbits. Statistical analysis showed significant differences in the ADC
      values between the normal control and liver fibrosis groups, and between the
      rabbits with different histopathological grades and fibrosis stages (P=0.000).
      CONCLUSIONS: Liver fibrosis results in significantly lowered ADC values of the
      liver depending on the histopathological grades and fibrosis stages. The
      pathological basis for these changes lies in reduced water content and restricted
      Brownian motion of water in the liver due to hepatocyte degeneration and
      swelling, inflammatory cell infiltration, and collagen fiber deposition in the
      interstitial space.

PMID- 19403420
TI  - [Renal protective effects of sulodexide in diabetic rats and its anti-oxidative
      mechanism].
AB  - OBJECTIVE: To investigate the renal protective effects of sulodexide and its anti
      oxidative stress mechanism in diabetic rats. METHOD: Thirty male SD rats were
      randomized into 3 equal groups, namely the control group, diabetic group, and
      sulodexide treatment group. Twelve weeks after establishment of rat diabetic
      models and administration of sulodexide, the rats were sacrificed for measurement
      of the urine volume, body mass, kidney mass/body weight ratio, plasma glucose,
      and glycosylated hemoglobin (HbA1c). Malondialdehyde (MDA) levels and superoxide
      dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) activities
      in the renal tissue or serum were tested. Electron microscopy was performed to
      observe the pathological changes in the kidneys. RESULTS: The urine volume, renal
      mass/body mass ratio, serum glucose, HbA1C, and serum and renal MDA levels all
      significantly increased in the diabetic rats in comparison with the normal
      controls (P<0.05). But the body weight and activities of SOD, CAT, and GSH-PX in
      the renal tissue in the normal control group were significantly higher than those
      in the diabetic and sulodexide group. After 12 weeks of sulodexide treatment,
      SOD, CAT, and GSH-PX activities in the renal tissue of rats were significantly
      increased in comparison with those in the diabetic rats (P<0.05). Electron
      microscopy showed obvious irregular thickening of the glomerular capillary
      basement membrane in the diabetic group with vacuolization in the mitochondria in
      the epithelial cells, and such pathological changes were significantly alleviated
      in the sulodexide treatment group. CONCLUSIONS: Sulodexide can effectively lower
      the urinary albumin excretion rate, improve the ultrastructural renal pathologies
      and prevent glomerular basement membrane thickening in diabetic rats, probably in
      association with the reduction of the MDA levels and enhancement of SOD, CAT, and
      GSH-PX activities.

PMID- 19403421
TI  - [Inhibitory effects of RNA interference on MMP-24 expression and invasiveness of
      ovarian cancer SKOV(3) cells].
AB  - OBJECTIVE: To investigate the inhibitory effect of RNA interference (RNAi) on MMP
      24 expression and invasiveness of ovarian cancer SKOV(3) cells. METHOD: Two pairs
      of small interfering RNA (siRNA) specific to MMP-24 mRNA were designed and
      transfected into SKOV(3) cells. RT-PCR and Western blotting were used to detect
      the mRNA and protein expressions of MMP-24, and the cell invasiveness was
      assessed using an in vitro invasion test. RESULTS: After transfection with siRNA,
      the mRNA and protein expression levels of MMP-24 were obviously reduced in
      SKOV(3) cells, which also showed significantly decreased invasiveness in vitro.
      CONCLUSIONS: MMP-24 gene silencing by RNAi can suppress the invasiveness of
      ovarian cancer SKOV(3) cells in vitro, which may provide a new therapeutic
      approach of ovarian cancer.

PMID- 19403423
TI  - [Application of Excel programs of Fisher exact probability test for medical
      data].
AB  - OBJECTIVE: To accomplish the computation of Fisher exact probability test for
      fourfold table data in Excel. METHOD: The computing program of exact probability
      method for medical data in fourfold table design was edited by employing the IF
      statement and the relevant functions, such as SUM, FACT, DSUM, etc in Excel. The
      computational results are compared and evaluated according to the case studies.
      RESULTS: The output of Fisher Exact Probability was generated and presented
      correctly following the input of four numerical values into the computation
      program in the setting of Excel. The parametric outcomes are in agreement with
      those produced by SAS and SPSS, in the combination tables containing the P value,
      two-tailed cumulative P value, left-tailed P-value, right-tailed P-value, Chi2
      values and P values both for direct Chi-squared test and corrected Chi-squared
      test. CONCLUSIONS: Direct Chi-squared test, corrected Chi-squared test combined
      with Fisher Exact Probability test for fourfold table data can be conveniently,
      rapidly, and accurately accomplished in Excel.

PMID- 19403422
TI  - [Features of ischemic myocardial contracture after asphyxia-induced cardiac
      arrest in rats].
AB  - OBJECTIVE: To investigate the features of ischemic myocardial contracture after
      asphyxial cardiac arrest in rats. METHOD: Asphyxial cardiac arrest was induced in
      8 Wistar rats, and the length and width of the heart were measured at the
      different time points after cardiac arrest. RESULTS: Obvious ischemic myocardial
      contracture occurred after the cardiac arrest, reaching the maximal contracture
      at 4-6 min after the arrest. CONCLUSIONS: Ischemic myocardial contracture induced
      by asphyxia may be an important factor affecting the outcome of cardiopulmonary
      resuscitation.

PMID- 19403424
TI  - [Video-assisted thoracoscopic extended thymectomy and transsternal extended
      thymectomy for treatment of myasthenia gravis: a case-control study].
AB  - OBJECTIVE: To compare the therapeutic effects of video-assisted thoracoscopic
      extended thymectomy (VATET) and transsternal extended thymectomy (TET) for
      myasthenia gravis (MG). METHOD: This study included 21 patients undergoing VATET
      through the "three holes" approach on the right chest and 32 undergoing TET with
      sternum dissection. The thymus was excised and the anterior mediastinum adipose
      tissue removed in both groups. RESULTS: VATET was associated with reduced
      intraoperative blood loss and longer operative time without the use of
      postoperative analgesics; very few patients were admitted into the intensive care
      unit (ICU), showing significant differences from the TET group (P<0.05). No
      significant difference was found between the two groups in tracheal tube removal
      time, length of stay in ICU, closed thoracic drainage removal time, and
      postoperative hospital stay, total hospital stay, postoperative complications,
      total hospitalization costs, or the rate of remission and improvement (P>0.05).
      CONCLUSIONS: Compared with TET, VATET requires only a small incision without
      leaving metal foreign body in the body, and the patients experience less
      postoperative pain and rapid recovery, with similar mid- and long-term clinical
      outcomes.

PMID- 19403426
TI  - [Effect of the drug-resistant attenuated Bacillus proteus on CD80 and CD86
      protein expression in peripheral blood dendritic cells of hepatitis B patients].
AB  - OBJECTIVE: To explore the effect of the drug-resistant attenuated Bacillus
      proteus on the protein expression of CD80 and CD86 in peripheral blood dendritic
      cells (DCs) of hepatitis B patients. METHOD: Peripheral blood monocytes were
      isolated from HBV-infected patients and the DCs were separated and induced to
      differentiate in vitro. The expression of CD80 and CD86 proteins on cultured DCs
      were examined using flow cytometry. RESULTS: The expression rate of CD80 and CD86
      of chronic hepatitis B patients increased significantly (P=0.000), while the
      positive expression rate of CD80 and CD86 showed no obvious variation in healthy
      individuals (P=0.185 and P=0.118, respectively). CONCLUSIONS: Bacillus proteus
      can significantly increase CD80- and CD86-positive cell percentage in peripheral
      blood DCs of HBV-infected patients, but has no such an effect in healthy
      individuals.

PMID- 19403425
TI  - [Investigation into the serum uric acid level of the residents in Henglan town of
      Zhongshan city].
AB  - OBJECTIVE: To investigate the relationship between cardiac Cerebrovascular
      disease and serum uric acid(SUA) in the coastal inhabitant, and try to provide
      base for prevention of the local metabolic disease and cardiac Cerebrovascular
      disease. METHOD: We got 3111 local people who had participated in the annual
      physical examination in the perch hospital for the research on the level of SUA
      and the relative risk factor. According to SUA level we divided the cases into
      two groups. One is hyperuricemia group and the other is control group. RESULTS:
      (1)The average SUA level was (380.2-/+62.58) micromol/L in the males, while
      (290.82-/+60.32) micromlo/L in the female. The sick rate of hyperuricaemia rate,
      was 21.8% for male, and the 17.6% of female. This disease affected more men than
      women. It has significant difference (P<0.01); (2)The SUA level of the showed a
      positive correlation with the indexes of the total cholesterol, the triglyceride,
      the blood pressure and the body weight index. The SUA level in overweight/obesity
      people was obviously higher than that of the normal weight people. CONCLUSIONS:
      (1)The sick rate of hyperuricaemia is high in Zhongshan coastal area, which due
      to many related factors. As far as, few people know it, so we should adopt the
      synthesis measure to prevent and control it to reduce the sick rate; (2)the rise
      of The SUA level possibly becomes one of the independent dangerous and predictive
      factor for the heart cerebral von disease.

PMID- 19403427
TI  - [Effect of local treatment with cooling and spray film on early edema of
      superficial II degree scald burns in rats].
AB  - OBJECTIVE: To investigate the anti-inflammatory effect of early local treatment
      with cooling and spray film on scald burn injury in rats. METHOD: Seventy-five
      Wistar rats were randomly divided into 5 groups including the sham-scalded group,
      untreated scald group, cooling group, spray film group, and cooling plus spray
      film group with corresponding treatments. After gross observation of the wounds,
      the tissues at the wounds were sampled at different time points after the injury
      to determine the total water content (wet: dry weight ratio) and prostaglandin
      E(2) (PGE(2)) levels using radioimmunoassay (RIA). RESULTS: Treatment with
      cooling and spray film significantly alleviated the swelling and effusion of the
      scald burns. At each of the time points, the water content and PGE(2) levels in
      the cooling group, spray film group and cooling plus spray film group were all
      lower than those in untreated scald group (P<0.01), but all higher than those in
      the sham-scalded group (P<0.01). The water content and PGE(2) levels were the
      lowest in cooling plus spray film group, and a significant correlation was noted
      between the water content and PGE(2) levels in the untreated scald group, cooling
      group, spray film group and cooling plus spray film group (P<0.01). CONCLUSIONS:
      Local treatment with cooling and spray film can alleviate the edema of
      superficial II degree scald burns in rats probably by reducing the levels of the
      inflammatory cytokines in the local tissues.

PMID- 19403428
TI  - [Relationship between cystatin C and cerebral infarction].
AB  - OBJECTIVE: To study the relationship between cystatin C and cerebral infarction
      and explore the role of cystatin C in the protection against cerebral infarction.
      METHOD: Eighty-three patients with cerebral infarction and 71 randomly selected
      age- and gender-matched patients in the Department of Neurology (control group)
      were enrolled in this study. Fasting whole blood (3 ml) was obtained from the
      patients in both groups and the sera were separated to determine the levels of
      cystatin C using particle reinforced immunoturbidimetric assay. RESULTS: The
      serum cystatin C level was significantly lower in the cerebral infarction group
      than in the control group (1.62-/+0.31 vs 2.23-/+0.22 mg/L, P<0.01). CONCLUSIONS:
      Cystatin C is closely related to cerebral infarction probably as a protective
      factor against cerebral infarction.

PMID- 19403429
TI  - [Correlation between white matter lesion and memory impairment in patients with
      obstructive sleep apnea syndrome].
AB  - OBJECTIVE: To investigate the nature of white matter lesion and correlation to
      memory impairment in patients with obstructive sleep apnea syndrome (OSAS) by
      diffusion tensor imaging ( DTI). METHOD: We conducted a cross-sectional study of
      20 middle-aged male people (10 with OSAS and 10 healthy controls) group-matched
      by age, educational level, and socioeconomic status. DTI was performed on those
      people with OSAS and on matched controls. Fractional anisotropy(FA) and average
      diffusion coefficient(ADC) values were measured respectively in bilateral white
      matter of the frontal lobe, anterior cingulate gyrus, anterior cingulum, etc. At
      the same time, WMS values were detected respectively. RESULTS: Relative to
      controls, patients with OSAS had a lower FA in the white matter of right frontal
      lobe (0.444-/+0.025), splenium of corpus callosum (0.776-/+0.028 ), left anterior
      cingulate gyrus (0.154-/+0.021), right anterior cingulate gyrus (0.152-/+0.017),
      left anterior cingulum (0.372-/+0.022), right anterior cingulum (0.351-/+0.029),
      left centrum semiovale (0.501-/+0.029), peripheric white matter of left anterior
      angle (0.242-/+0.031), peripheric white matter of left posterior angle (0.338
      /+0.029), peripheric white matter of right posterior angle (0.360-/+0.022 ), left
      parahippocampal gyrus (0.167-/+0.027), right parahippocampal gyrus (0.177
      /+0.023). Besides, FA values of OSAS patients in the white matter of right
      frontal lobe and left centrum semiovale were strongly positively correlated with
      WMS values. While in comparison with that of healthy controls, ADC of OSAS
      patients was significantly higher in the white matter of right frontal lobe
      (8.589-/+0.264 x e(-10) mm(2)/s), trunk of corpus callosum (8.197-/+0.253 x e(
      10) mm(2)/s), splenium of corpus callosum (8.218-/+0.194 x e(-10) mm(2)/s), left
      anterior cingulate gyrus (12.151-/+0.454 x e(-10) mm(2)/s), right anterior
      cingulate gyrus (12.113-/+0.524 x e(-10) mm(2)/s), right anterior cingulum (8.954
      /+0.177 x e(-10) mm(2)/s),left centrum semiovale (7.333-/+0.220 x e(-10) mm(2)/s)
      and peripheric white matter of left anterior angle (9.186-/+0.465 x e(-10)
      mm(2)/s). CONCLUSIONS: This study indicated that white matter and gray matter was
      both remarkably damaged in OSAS patients, which could contribute to memory
      impairment.

PMID- 19403430
TI  - [Undifferentiated connective tissue disease].
AB  - Evolution of immunopathological diseases is usually slow and progressive. Non
      differentiated collagen disease (NDC) or the term "undifferentiated connective
      tissue disease" (UCTD) represents a stage of disease where clinical symptoms and
      serological abnormalities suggest autoimmune disease, but they are not sufficient
      to fulfill the diagnostic criteria of any well-established connective tissue
      disease (CTD) such as systemic lupus erythematosus (SLE), Sjogren's syndrome,
      mixed connective tissue disease (MCTD), systemic sclerosis (SSc), polymyositis/
      dermatomyositis (PM/DM) or rheumatoid arthritis (RA). 30-40 percent of patients
      presenting undifferentiated profile develops and reaches the stage of a well
      defined systemic autoimmune disease during five years follow up, while 60 percent
      remains in an undifferentiated stage.In the stage of NDC, immunoregulatory
      abnormalities and endothelial dysfunction are present. In conclusion, NDC
      represents a dynamic state, and it is important to recognize the possibility of a
      progression to a definite systemic autoimmune disease.

PMID- 19403431
TI  - [Recent perspectives on the development of the central nervous system and the
      genetic background of neural tube defects].
AB  - Neural tube defects are rare and mostly lethal malformations. The pattern of
      inheritance of these malformations is multifactorial, rendering the
      identification of the underlying causes. Numerous studies have been conducted to
      elucidate the genetic basis of the development of the central nervous system.
      Essential signaling pathways of the development of the central nervous system
      include the planar cell polarity pathway, which is important for the initiation
      of neural tube closure as well as sonic hedgehog pathway, which regulates the
      neural plate bending. Genes and their mutations influencing the different stages
      of neurulation have been investigated for their eventual role in the development
      of these malformations. Among the environmental factors, folic acid seems to be
      the most important modifier of the risk of human neural tube defects. Genes of
      the folate metabolism pathways have also been investigated to identify mutations
      resulting in increased risk of NTDs. In this review the author has attempted to
      summarize the knowledge on neural tube defects, with special regard to genetic
      factors of the etiology.

PMID- 19403432
TI  - [Probiotics in gastrointestinal disorders].
AB  - Probiotics are preparations containing viable microorganisms that confer
      potential health benefits for the host. Alteration of bacterial flora both in
      terms of specific content and concentration may be beneficial in many
      gastrointestinal disorders. Probiotics are widely used for the management of
      these conditions in many countries. However, mechanisms of probiotics are
      incompletely understood. Benefits observed clinically with one species or
      combinations of species can not be generalized. The optimal dose of treatment has
      to be determined. Although probiotics are generally regarded safe, caution is
      needed when using these supplements routinely. It has been proved, that severe
      adverse events can occur as a complication of probiotic treatment. This review
      summarizes the recent knowledge concerning the use of probiotics in
      gastrointestinal disorders.

PMID- 19403433
TI  - [Civilization stress, cardiovascular risk, evidence-based medicine, guidelines].
AB  - Cardiovascular diseases have the pole-position on the list of morbidity and
      mortality statistics. Despite the great advances have been made in management of
      cardiovascular diseases, prevalence of these disorders increases worldwide, and
      even younger and younger ages are threatened. This phenomenon is strongly related
      to obesity and type 2 diabetes pandemic, which shows an unequivocal association
      with expansion of modernized life-style. The pathomechanism proposed to have
      central role is the chronic stress induced by civilized life-conduct. The authors
      criticizes the everyday practice suggested for management of cardiovascular
      diseases, focusing on normalization of cardiovascular risk factors, instead of
      fighting against the primary cause ie. chronic stress. There is growing evidence,
      that achieving the target values defined in guide-lines will not necessarily
      result in improvement of patient related clinical outcomes. The statistical
      approach generally practiced in randomized clinical trials is primarily striving
      for the drug-sale, instead of discovering novel pathophysiological relations.
      Pharmaceutical industry having decisive role in research and patient-care is
      mainly interested in profit-sharing, therefore patients' interest can not be
      optimally realized, and costs are unnecessarily augmented. Separation of patient
      , and business-oriented medical care is an ethical question of fundamental
      importance.

PMID- 19403434
TI  - [Can the decrease of blood alcohol level be accelerated? Results of a clinical
      study].
AB  - The purpose of this study was to examine the effect of Guardian Angel powder (GA)
      on the blood alcohol level. According to the experimental protocol, two sets of
      measurement were performed: modeling the eating and drinking habit of a typical
      family or social meeting, alcohol containing drinks corresponding to 70 g of pure
      alcohol and copious amount of food were consumed first without GA powder, then
      with GA powder. In the latter case GA powder was dissolved in water and one dose
      was taken before eating, the other one was consumed during eating. Blood samples
      were hourly collected from the volunteers in both sets for four hours. The
      measurement of blood alcohol level was performed by gas chromatography-mass
      spectrometry method proceeding to Solid Phase Micro Extraction (SPME). Our
      results show that the blood alcohol level decreased significantly when two doses
      of GA powder were consumed. After two hours of taking GA powder, the blood
      alcohol level was significantly lower in each volunteers compared to their own
      blood alcohol level measured in the absence of GA powder. This result shows that
      the individual variation of the alcohol metabolism does not influence
      significantly the effect of GA powder. Further studies are needed to investigate
      the detailed mechanism of the action of GA powder to find out whether GA powder
      influences the absorption of alcohol or/and the metabolism of alcohol.

PMID- 19403437
TI  - Chronic, in vivo, PPARalpha activation prevents lipid overload in rat liver
      induced by high fat feeding.
AB  - PURPOSE: Peroxisome proliferator-activated receptors (PPAR's) are lipid sensors
      and when activated they modify gene expression of proteins regulating fatty acid
      (FA) metabolism in liver cells. The aim of the present study was to examine the
      in vivo effects of PPAR alpha and gamma activation combined with high fat diet
      (HFD) feeding on the lipid content and FA profile in the liver. MATERIAL/METHODS:
      We assessed whether in vivo activation of PPARs (alpha or gamma) affects lipid
      accumulation in the liver induced by HFD feeding. Furthermore, as PPAR activity
      may be a key factor regulating long chain fatty acids (LCFA) flux and subsequent
      LCFA utilization in the liver, we prompted to investigate also the FA profile in
      different lipid fractions in this tissue. RESULTS: PPARalpha agonist (WY 14,643)
      treatment reduced the accumulation of liver lipids free fatty acids (FFA:-30%,
      diacylglycerols DAG: -27% and triacylglycerols TAG: -60%, p<0.05) evoked by HFD
      feeding. Interestingly, with PPARgamma stimulation liver lipid content was
      further elevated comparing to the effects of HFD (phospholipids PL: +48%, DAG:
      +231%, TAG: +346%, p<0.05). CONCLUSIONS: These findings suggest that in vivo
      PPARalpha and PPARgamma activation combined with HFD feeding exert different
      effects on lipid content in rat's liver and in vivo PPARalpha activation may
      prevent lipid overload in the liver cells provoked by HFD feeding.

PMID- 19403438
TI  - The influence of Chlamydia trachomatis infection on spontaneous abortions.
AB  - PURPOSE: The aim of the study was to evaluate the frequency of Chlamydia
      trachomatis (C.t.) infection among women who experienced a miscarriage. MATERIALS
      AND METHODS: Patients referred to the Centre for STD Research and Diagnostics in
      Bialystok from the Department of Perinatology and from gynaecological outpatient
      clinics, after spontaneous abortion were enrolled in the study. C.t. infection
      diagnostics were performed among 76 women with 1 miscarriage and 44 patients with
      > or =2 miscarriages in anamnesis. Forty-six patients in the 2nd and the 3rd
      trimester of normal pregnancy served as a comparative group. Endocervical swabs
      as well as blood serum were obtained. To detect chlamydial DNA, direct PCR method
      was performed (Roche, Molecular Systems, N.J., USA). To detect IgA and IgG
      specific anti-chlamydial antibodies we used immunoenzymatic assay (medac,
      Hamburg, Germany). RESULTS: In patients with 1 miscarriage (gr.1), C.t. infection
      by means of PCR was detected in 11.8% of women (p=0.029), in patients with > or
      =2 miscarriages (gr.2) in 9.1% (p=0.198) and in the comparative group (gr.0) in
      2.2%. Specific anti-chlamydial antibodies IgA class were detected in: 7.9
      (p=0.082) in group 1, 4.5% (p=0.236) in group 2 and in 0% in group 0, and IgG
      class in 21.1% (p=0.024), 36.4% (p=0.000) and in 4.4%, respectively. CONCLUSIONS:
      1. C.t. infection is an important causative agent of miscarriages in women. 2.
      C.t. infection diagnostic procedures should be considered in screening tests
      during pregnancy.

PMID- 19403439
TI  - Prevalence and correlates of depression among patients with head and neck cancer:
      a systematic review of implications for research.
AB  - PURPOSE/OBJECTIVES: To present a comprehensive summary of the existing research
      literature related to prevalence and correlates of depression in adult patients
      with head and neck cancer to establish a knowledge base for future research. DATA
      SOURCES: Quantitative studies in English measuring depression or mood in adults
      with head and neck cancer published from 1986-2008. DATA SYNTHESIS: A substantial
      body of knowledge exists regarding prevalence, correlates, and predictors of
      depression in patients with head and neck cancer. Prevalence rates of depression
      are high at diagnosis, during treatment, and in the first six months following
      treatment, and mild to moderate depression may continue for three to six years
      after diagnosis. Certain patient demographic characteristics (e.g., marital
      status, education), symptoms, and specific time points in the illness trajectory
      (e.g., time of treatment) are correlated with depression. Specific patient
      variables at diagnosis, such as depression, can predict depression at later time
      points. CONCLUSIONS: Additional research should assess symptoms using consistent
      depression instruments or clinical interviews based on specific criteria in
      patients with head and neck cancer. Specifically, multisite studies should be
      conducted to increase sample sizes. Research related to symptom clusters and the
      effect of clusters on patients is needed. Longitudinal studies that examine
      depression and patient characteristics, symptoms, type of treatments, and the
      correlates of depression across the trajectory of illness are important.
      Replication of existing research using multiple patient and clinical
      characteristics to explore predictors of depression may reveal profiles for
      patients most at risk. IMPLICATIONS FOR NURSING: This comprehensive summary of
      existing research literature related to the prevalence and correlates of
      depression among adult patients with head and neck cancer provides evidence-based
      information that can be used by oncology nurses in their practice.

PMID- 19403440
TI  - Continued family smoking after lung cancer diagnosis: the patient's perspective.
AB  - PURPOSE/OBJECTIVES: To explore the influence of lung cancer diagnosis on
      interpersonal dynamics in families in which one or more members continue to smoke
      following diagnosis. RESEARCH APPROACH: Descriptive, qualitative. SETTING: Three
      cancer care sites in western Canada. PARTICIPANTS: 16 participants from 8 family
      dyads. METHODOLOGIC APPROACH: Patients with lung cancer receiving treatment and
      immediate family members were recruited to participate in individual or conjoint
      semistructured interviews. Thematic analysis was conducted on transcribed
      interviews. MAIN RESEARCH VARIABLES: Intrafamily interaction patterns, smoking
      and smoking cessation, lung cancer diagnosis. FINDINGS: Following diagnosis,
      patients with lung cancer experienced considerable distress as they struggled to
      understand family members' continued smoking. Patient orientations to family
      members who smoked included preserving relationships (maintaining harmony and
      connection with family members took priority over directly intervening with
      smokers) and risking relationships (patients repeatedly confronted family members
      about continued smoking to influence their cessation despite the impact on
      relationships). Neither pattern was successful in engaging relatives in smoking
      reduction or cessation, and the risking relationships approach resulted in
      conflict and strained family relationships. CONCLUSIONS: The findings provide
      additional support for examining family dynamics related to tobacco reduction and
      cessation as well as directions for future research. INTERPRETATION: Nurses
      should encourage tobacco reduction as a supportive intervention for patients with
      lung cancer and their families to eliminate smoking-related distress.

PMID- 19403441
TI  - An individualized representational intervention to improve symptom management
      (IRIS) in older breast cancer survivors: three pilot studies.
AB  - PURPOSE/OBJECTIVES: To test the feasibility and acceptability of an
      individualized representational intervention to improve symptom management (IRIS)
      in older breast cancer survivors and test the short-term effects of an IRIS on
      symptom distress. DESIGN: Two small randomized clinical trials and one pre
      experimental study. SETTING: Oncology clinic and community. SAMPLE: 41 women with
      breast cancer (aged 65 years and older) in pilot study 1, 20 in pilot study 2,
      and 21 in pilot study 3. METHODS: In pilot study 1, women were randomized to the
      IRIS or usual care control. In pilot study 2, women were randomized to the IRIS
      or delayed IRIS (wait list) control. In pilot study 3, all women received the
      IRIS by telephone. Measures were collected at baseline, postintervention, and
      follow-up (up to four months). MAIN RESEARCH VARIABLES: Feasibility,
      acceptability, symptom distress, symptom management behaviors, symptom management
      barriers, and quality of life. FINDINGS: Across three pilot studies, 76% of
      eligible women participated, 95% completed the study, 88% reported the study was
      helpful, and 91% were satisfied with the study. Some measures of symptom distress
      decreased significantly after the IRIS, but quality of life was stable. Women in
      the IRIS group changed their symptom management behaviors more than controls.
      CONCLUSIONS: Preliminary evidence supports the need for and feasibility of an
      IRIS. IMPLICATIONS FOR NURSING: Nurses may help older breast cancer survivors
      manage their numerous chronic symptoms more effectively by assessing women's
      beliefs about their symptoms and their current symptom management strategies.

PMID- 19403442
TI  - The effects of sense of coherence, demands of illness, and social support on
      quality of life after surgery in patients with gastrointestinal tract cancer.
AB  - PURPOSE/OBJECTIVES: To examine the relationship between quality of life (QOL) as
      an index of adaptation status and concepts related to self-care skills of
      patients who have been diagnosed with and undergone surgery for digestive system
      cancer: sense of coherence (SOC), social support, demands of illness, and the
      thought "Why me?" DESIGN: Cross-sectional survey. SETTING: General hospitals in
      Japan. SAMPLE: 60 patients who had been newly diagnosed with digestive system
      cancer and had undergone surgery. METHODS: Questionnaires were distributed to
      participants whose discharge date had been determined. The questionnaires were
      returned through the mail within two weeks of the discharge date. MAIN RESEARCH
      VARIABLES: QOL, SOC, social support, demands of illness, and the thought "Why
      me?" FINDINGS: QOL was strongly correlated with SOC and the demands of illness
      and was moderately correlated with social support. The only variable that was
      negatively correlated with SOC was the question, "Why me?" SOC and demands of
      illness accounted for 54% of the variance in QOL; social support was not a
      significant factor. CONCLUSIONS: This study suggests that SOC is positively
      correlated with QOL and the demands of illness are negatively correlated with QOL
      among study participants. IMPLICATIONS FOR NURSING: Nursing interventions
      focusing on SOC and illness demands may have a significant effect on QOL of
      patients following cancer surgery.

PMID- 19403443
TI  - Depression and perceptions of quality of life of breast cancer survivors and
      their male partners.
AB  - PURPOSE/OBJECTIVES: To assess differences in ways women with breast cancer
      evaluate their own quality of life (QOL) compared to perceptions of their
      partners and to identify factors that influence dissimilarities in QOL
      perceptions. DESIGN: Cross-sectional study. SETTING: Breast unit in southern
      Brazil. SAMPLE: 73 women with stage I-III breast cancer and their partners. Most
      participants were middle-aged, with partners of long-term cohabitation. METHODS:
      QOL was evaluated with the World Health Organization Quality of Life-Brief Form
      (WHOQOL-BREF), Beck Depression Inventory, and WHOQOL-BREF adapted for a third
      person. MAIN RESEARCH VARIABLES: Demographic and clinical features, QOL,
      partners' perceptions, and depression. FINDINGS: No differences were found
      between the perceptions of QOL in different domains between the patients and
      their partners. Depression in women seemed to be the only variable that
      interfered in a consistent manner with the congruity of the QOL assessments made
      by patients and their partners. CONCLUSIONS: Partners of women with breast cancer
      may be viewed as reliable surrogates to assess patients' QOL. IMPLICATIONS FOR
      NURSING: Partners' judgments of patients' QOL may be important in some
      circumstances, particularly when patients are not able to answer questions about
      their own QOL because of cognitive or functional limitations. Nurses must be
      aware that partners are the most frequent informal caregivers and should be
      included in the entire treatment process.

PMID- 19403444
TI  - Complementary and alternative medicine used by pediatric patients with cancer in
      western Turkey.
AB  - PURPOSE/OBJECTIVES: To determine the extent of complementary and alternative
      medicine (CAM) use, the types of therapies employed, and the reasons for choosing
      those therapies. DESIGN: Descriptive type, cross-sectional. SETTING: Pediatric
      oncology department in western Turkey. SAMPLE: 112 children receiving or
      completing treatment for cancer. METHODS: Parents of 112 children completed a
      questionnaire regarding CAM use. Analyses included examining correlations between
      CAM use and demographic variables. MAIN RESEARCH VARIABLES: CAM use and
      demographic variables. FINDINGS: 77% of the patients used one or more type of
      CAM, with herb use being the most common. CONCLUSIONS: About 75% of parents used
      CAM for their children. However, about 25% sought discussion with the physician
      about the CAM they were using. IMPLICATIONS FOR NURSING: Nurses should approach
      their patients without prejudice, gather information about the various CAM
      techniques, and share this knowledge with their patients.

PMID- 19403446
TI  - A day without a nurse.

PMID- 19403448
TI  - The critical role of oncology nurse practitioners in cancer care: future
      implications.

PMID- 19403449
TI  - Sexual side effects in women with anal carcinoma.

PMID- 19403450
TI  - Correlates of adherence to supervised exercise in patients awaiting surgical
      removal of malignant lung lesions: results of a pilot study.
AB  - PURPOSE/OBJECTIVES: To examine the demographic, medical, and social-cognitive
      correlates of adherence to a presurgical exercise training intervention in
      patients awaiting surgery for suspected malignant lung lesions. DESIGN: Pilot
      study, single-group, prospective design with convenience sampling. SETTING:
      Exercise training was performed at a university research fitness center in
      western Canada. SAMPLE: 19 patients awaiting surgical resection of suspected
      malignant lung lesions. METHODS: At baseline, participants completed a
      questionnaire including the Theory of Planned Behavior variables of perceived
      behavioral control, attitude, and subjective norm, as well as medical and
      demographic information. Participants were asked to attend five supervised
      exercise sessions per week during surgical wait time (X = 8 +/- 2.4 weeks). MAIN
      RESEARCH VARIABLES: Theory of Planned Behavior variables and exercise adherence.
      FINDINGS: Adherence to the exercise intervention was 73% (range = 0%-100%).
      Correlates of adherence were perceived behavioral control (r = 0.63; p = 0.004)
      and subjective norm (r = 0.51; p = 0.014). Participants with greater than 80%
      adherence reported significantly higher behavioral control than participants with
      less than 80% adherence (X difference = 1.1; 95% confidence interval = 0.1-2.2; p
      = 0.035). Men had better adherence than women (X difference = 24.9%; 95%
      confidence interval = 0.4-49.4; p = 0.047). CONCLUSIONS: Perceived behavioral
      control and subjective norm were the strongest correlates of exercise adherence.
      Women could be at risk for poor exercise adherence prior to lung surgery.
      IMPLICATIONS FOR NURSING: This information could be useful for clinicians in
      their attempts to improve adherence to exercise interventions in patients
      awaiting surgery for malignant lung lesions.

PMID- 19403451
TI  - Spiritual well-being and practices among women with gynecologic cancer.
AB  - PURPOSE/OBJECTIVES: To identify spiritual well-being and spiritual practices in
      women with gynecologic cancer. DESIGN: Descriptive, cross-sectional. SETTING:
      Urban and rural communities in southeast Florida. SAMPLE: Convenience sample of
      85 women (X age = 65.72 years) with some form of gynecologic cancer. METHODS:
      Participants completed questionnaires to assess spiritual well-being and
      spiritual practices while attending a healthcare clinic. MAIN RESEARCH VARIABLES:
      Spiritual well-being, spiritual practices. FINDINGS: The level of overall
      spiritual well-being was high, as were the levels of self-efficacy and life
      scheme (meaningfulness), as measured with two subscales. Most women reported use
      of several spiritual practices, including family activities, exercise, and
      listening to music. CONCLUSIONS: Additional study of the spiritual well-being and
      practices of women with cancer and comparisons with other groups of women are
      needed. IMPLICATIONS FOR NURSING: Nurses can assume a role in encouraging
      spiritual practices and enhancing spiritual well-being in women with cancer.

PMID- 19403452
TI  - Underestimation of breast cancer risk: influence on screening behavior.
AB  - PURPOSE/OBJECTIVES: To describe perceived breast cancer risk, identify the
      percentage of women with inaccurate risk perceptions, and examine the influence
      of perceived and objective risk on screening behavior. DESIGN: Descriptive,
      correlational, cross-sectional. SETTING: Community settings in a metropolitan
      area on the western coast of the United States. SAMPLE: Multicultural sample of
      184 English-speaking women (57% non-Caucasian, X age = 47 +/- 12 years) who have
      never been diagnosed with cancer. METHODS: Two perceived risk scales (verbal and
      comparative) and the Gail model were used to assess perceived and objective
      breast cancer risk, respectively. MAIN RESEARCH VARIABLES: Perceived breast
      cancer risk, objective breast cancer risk, screening behavior. FINDINGS:
      Participants reported that they "probably will not" get breast cancer and that
      their risk was "somewhat lower" than average. Family history of breast cancer was
      a significant predictor of perceived risk. Demographic characteristics and
      objective risk factors were not associated with perceived risk. Most women at
      high risk for breast cancer (89%) underestimated their actual risk; fewer women
      with low to average risk for breast cancer (9%) overestimated their risk. Age,
      Gail scores, and health insurance status promoted breast cancer screening;
      underestimation of risk had the opposite effect. CONCLUSIONS: Inaccurate
      perceptions of risk do not promote optimal breast cancer screening. The finding
      has implications for most women at high risk for developing breast cancer who
      underestimate their risk. IMPLICATIONS FOR NURSING: Oncology nurses can use risk
      assessment tools to provide individualized counseling regarding breast cancer
      risk factors and screening. Women at high risk who underestimate their risk could
      benefit from additional screening and from advances in cancer chemoprevention.

PMID- 19403455
TI  - Topics covered in this issue of Human Genomics: the existence of ALDH2*2 in the
      Indian population, novel prediction methods for transcription factor binding
      sites, molecular technologies and bioinformatic tools, and Hox gene expression.

PMID- 19403456
TI  - Association of ADH1B and ALDH2 gene polymorphisms with alcohol dependence: a
      pilot study from India.
AB  - Functional polymorphism in the genes encoding alcohol dehydrogenase (ADH) 1B and
      aldehyde dehydrogenase (ALDH) 2 are considered most important among several
      genetic determinants of alcohol dependence, a complex disorder. There is no
      report on the widely studied Arg47His and Glu487Lys polymorphisms from Indian
      alcohol-dependent populations. In this paper, we report, for the first time,
      allelic and genotypic frequencies of Arg47His and Glu487Lys single nucleotide
      polymorphisms (SNPs) in North Indian alcohol-dependent subjects. A total of 174
      alcohol-dependent males, recruited using DSM IV criteria (American Psychiatric
      Association, 1994), were genotyped using the polymerase chain reaction
      restriction fragment length polymorphism method. The results obtained from
      genetic analysis were correlated with clinical parameters using Student's t-test
      or Mann Whitney's U test. The highlight of the study findings was the uniquely
      high frequency of the ALDH2*2/*2 genotype (among alcohol-dependent subjects)
      being a risk-conferring factor for alcohol dependence.

PMID- 19403457
TI  - A general integrative genomic feature transcription factor binding site
      prediction method applied to analysis of USF1 binding in cardiovascular disease.
AB  - Transcription factors are key mediators of human complex disease processes.
      Identifying the target genes of transcription factors will increase our
      understanding of the biological network leading to disease risk. The prediction
      of transcription factor binding sites (TFBSs) is one method to identify these
      target genes; however, current prediction methods need improvement. We chose the
      transcription factor upstream stimulatory factor 1 ( USF1 ) to evaluate the
      performance of our novel TFBS prediction method because of its known genetic
      association with coronary artery disease (CAD) and the recent availability of
      USF1 chromatin immunoprecipitation microarray (ChIP-chip) results. The specific
      goals of our study were to develop a novel and accurate genome-scale method for
      predicting USF1 binding sites and associated target genes to aid in the study of
      CAD. Previously published USF1 ChIP-chip data for 1 per cent of the genome were
      used to develop and evaluate several kernel logistic regression prediction
      models. A combination of genomic features (phylogenetic conservation, regulatory
      potential, presence of a CpG island and DNaseI hypersensitivity), as well as
      position weight matrix (PWM) scores, were used as variables for these models. Our
      most accurate predictor achieved an area under the receiver operator
      characteristic curve of 0.827 during cross-validation experiments, significantly
      outperforming standard PWM-based prediction methods. When applied to the whole
      human genome, we predicted 24,010 USF1 binding sites within 5 kilobases upstream
      of the transcription start site of 9,721 genes. These predictions included 16 of
      20 genes with strong evidence of USF1 regulation. Finally, in the spirit of
      genomic convergence, we integrated independent experimental CAD data with these
      USF1 binding site prediction results to develop a prioritised set of candidate
      genes for future CAD studies. We have shown that our novel prediction method,
      which employs genomic features related to the presence of regulatory elements,
      enables more accurate and efficient prediction of USF1 binding sites. This method
      can be extended to other transcription factors identified in human disease
      studies to help further our understanding of the biology of complex disease.

PMID- 19403458
TI  - Exploring the relationship between polymorphic (TG/CA)n repeats in intron 1
      regions and gene expression.
AB  - The putative role of (TG/CA)n repeats in the regulation of transcription has
      recently been reported for several cancer- and disease-related genes, including
      the genes encoding the epidermal growth factor receptor (EGFR), hydroxysteroid
      (11-beta) dehydrogenase 2 (HSD11B2) and interferon-gamma (IFNG). These studies
      indicated a correlation between gene expression levels and the presence or length
      of (TG/CA)n repeats in their intron 1 regions. A genome-wide search for genes
      with similar features may provide evidence of whether these dinucleotide repeats
      represent a class of universal regulators of gene expression, which has recently
      begun to be investigated as a quantitative complex phenotype. Using a public
      database of simple repeats, we identified 330 genes containing potentially
      polymorphic long (TG/CA)n repeats (n >or= 12) in their intron 1 regions. One
      known physiological pathway, the calcium signalling pathway, was found to be
      enriched among the genes containing long repeats. In addition, certain biological
      processes, such as cation transport, signal transduction and ion transport, were
      found to be enriched in these genes. Genotyping of the long repeats showed that
      the majority of these dinucleotide repeats were polymorphic in the HapMap CEU
      (Caucasians from Utah, USA) samples of northern and western European ancestry.
      Evidence for a significant association between these repeats and gene expression
      was not observed in the genes selected based on their expression profiles in the
      HapMap CEU samples. Our current findings, therefore, do not support a role for
      these repeats as a class of universal gene expression regulators. A more
      comprehensive evaluation of the relationship between these repeats and gene
      expression, potentially in other tissues, may be necessary to illustrate their
      roles in gene regulation in the future.

PMID- 19403459
TI  - Approaches to analyse dynamic microbial communities such as those seen in cystic
      fibrosis lung.
AB  - Microbial communities play vital roles in many aspects of our lives, although our
      understanding of microbial biogeography and community profiles remains unclear.
      The number of microbes or the diversity of the microbes, even in small
      environmental niches, is staggering. Current microbiological methods used to
      analyse these communities are limited, in that many microorganisms cannot be
      cultured. Even for the isolates that can be cultured, the expense of identifying
      them definitively is much too high to be practical. Many recent molecular
      technologies, combined with bioinformatic tools, are raising the bar by improving
      the sensitivity and reliability of microbial community analysis. These tools and
      techniques range from those that attempt to understand a microbial community from
      their length heterogeneity profiles to those that help to identify the strains
      and species of a random sampling of the microbes in a given sample. These
      technologies are reviewed here, using the microbial communities present in the
      lungs of cystic fibrosis patients as a paradigm.

PMID- 19403461
TI  - A biophysical mechanism may control the collinearity of Hoxd genes during the
      early phase of limb development.
AB  - A biophysical model has been proposed which deals with the observed collinearity
      of Hox gene expressions in developing vertebrate limbs. It is assumed that
      physical forces gradually dislocate the genes of the Hoxd cluster from inside the
      chromosome territory into the interchromosome domain, where the genes are
      activated. In particular, the action of Coulomb electric forces has been
      estimated in detail. Genetic engineering experiments (deletions, duplications and
      transpositions) were recently reported for Hoxd expression during limb
      development. Here, we analyse these results and show that the biophysical model
      explains them successfully.

PMID- 19403460
TI  - Pharmacogenetics of antidepressant response: an update.
AB  - The past few decades have witnessed much progress in the field of
      pharmacogenetics. The identification of the genetic background that regulates the
      antidepressant response has benefited from these advances. This review focuses on
      the pharmacogenetics of the antidepressant response through the analysis and
      discussion of the most compelling evidence in this line of research. Online
      databases (Medline and PsycINFO) have been searched and the most replicated
      association findings relating to the genetics of the antidepressant response have
      been reported and discussed. Some replicated findings in the literature have
      suggested the serotonin transporter promoter (5-HTTLPR), serotonin receptor 1A
      (HTR1A), serotonin receptor 2A (HTR2A), brain derived neurotrophic factor (BDNF),
      corticotropin releasing hormone receptor 1 (CRHR1) and FK506 binding protein 5
      (FKBP5) as putative regulators of the antidepressant response. A high rate of
      failure of replication has also been reported. Pharmacogenetics will hopefully
      provide the basis for personalised antidepressant treatment that is able to
      maximise the probability of a good response and to minimise side effects;
      however, this goal is not achievable at the moment. The extent of the validity of
      the replicated findings and the reasons for the poor results obtained from
      studies of the pharmacogenetics of the antidepressant response are discussed.

PMID- 19403462
TI  - Human ATP-binding cassette (ABC) transporter family.
AB  - There exist four fundamentally different classes of membrane-bound transport
      proteins: ion channels; transporters; aquaporins; and ATP-powered pumps. ATP
      binding cassette (ABC) transporters are an example of ATP-dependent pumps. ABC
      transporters are ubiquitous membrane-bound proteins, present in all prokaryotes,
      as well as plants, fungi, yeast and animals. These pumps can move substrates in
      (influx) or out (efflux) of cells. In mammals, ABC transporters are expressed
      predominantly in the liver, intestine, blood-brain barrier, blood-testis barrier,
      placenta and kidney. ABC proteins transport a number of endogenous substrates,
      including inorganic anions, metal ions, peptides, amino acids, sugars and a large
      number of hydrophobic compounds and metabolites across the plasma membrane, and
      also across intracellular membranes. The human genome contains 49 ABC genes,
      arranged in eight subfamilies and named via divergent evolution. That ABC genes
      are important is underscored by the fact that mutations in at least 11 of these
      genes are already known to cause severe inherited diseases (eg cystic fibrosis
      and X-linked adrenoleukodystrophy [X-ALD]). ABC transporters also participate in
      the movement of most drugs and their metabolites across cell surface and cellular
      organelle membranes; thus, defects in these genes can be important in terms of
      cancer therapy, pharmacokinetics and innumerable pharmacogenetic disorders.

PMID- 19403463
TI  - Protein-protein interaction databases: keeping up with growing interactomes.
AB  - Over the past few years, the number of known protein-protein interactions has
      increased substantially. To make this information more readily available, a
      number of publicly available databases have set out to collect and store protein
      protein interaction data. Protein-protein interactions have been retrieved from
      six major databases, integrated and the results compared. The six databases (the
      Biological General Repository for Interaction Datasets [BioGRID], the Molecular
      INTeraction database [MINT], the Biomolecular Interaction Network Database
      [BIND], the Database of Interacting Proteins [DIP], the IntAct molecular
      interaction database [IntAct] and the Human Protein Reference Database [HPRD])
      differ in scope and content; integration of all datasets is non-trivial owing to
      differences in data annotation. With respect to human protein-protein interaction
      data, HPRD seems to be the most comprehensive. To obtain a complete dataset,
      however, interactions from all six databases have to be combined. To overcome
      this limitation, meta-databases such as the Agile Protein Interaction Database
      (APID) offer access to integrated protein-protein interaction datasets, although
      these also currently have certain restrictions.

PMID- 19403464
TI  - Health professionals' attitudes towards using a Web 2.0 portal for child and
      adolescent diabetes care: qualitative study.
AB  - BACKGROUND: The Internet, created and maintained in part by third-party
      apomediation, has become a dynamic resource for living with a chronic disease.
      Modern management of type 1 diabetes requires continuous support and problem
      based learning, but few pediatric clinics offer Web 2.0 resources to patients as
      part of routine diabetes care. OBJECTIVES: To explore pediatric practitioners'
      attitudes towards the introduction of a local Web portal for providing young type
      1 diabetes patients with interactive pedagogic devices, social networking tools,
      and locally produced self-care and treatment information. Opportunities and
      barriers related to the introduction of such systems into clinical practice were
      sought. METHODS: Twenty clinicians (seven doctors, nine nurses, two dieticians,
      and two social welfare officers) from two pediatric diabetes teams participated
      in the user-centered design of a local Web 2.0 portal. After completion of the
      design, individual semi-structured interviews were performed and data were
      analyzed using phenomenological methods. RESULTS: The practitioners reported a
      range of positive attitudes towards the introduction of a local Web 2.0 portal to
      their clinical practice. Most interviewees were satisfied with how the portal
      turned out, and a sense of community emerged during the design process and
      development of the portal's contents. A complementary role was suggested for the
      portal within the context of health practice culture, where patients and their
      parents would be able to learn about the disease before, between, and after
      scheduled contacts with their health care team. Although some professionals
      expected that email communication with patients and online patient information
      would save time during routine care, others emphasized the importance of also
      maintaining face-to-face communication. Online peer-to-peer communication was
      regarded as a valuable function; however, most clinicians did not expect that the
      portal would be used extensively for social networking amongst their patients.
      There were no major differences in attitudes between different professions or
      clinics, but some differences appeared in relation to work tasks. CONCLUSIONS:
      Experienced clinical practitioners working in diabetes teams exhibited positive
      attitudes towards a Web 2.0 portal tailored for young patients with type 1
      diabetes and their parents. The portal included provision of third-party
      information, as well as practical and social means of support. The practitioners'
      early and active participation provides a possible explanation for these positive
      attitudes. The findings encourage close collaboration with all user groups when
      implementing Web 2.0 systems for the care of young patients with chronic
      diseases, particularly type 1 diabetes. The study also highlights the need for
      efforts to educate clinical practitioners in the use of Web publishing, social
      networking, and other Web 2.0 resources. Investigations of attitudes towards
      implementing similar systems in the care of adults with chronic diseases are
      warranted.

PMID- 19403465
TI  - Methodological challenges in online trials.
AB  - Health care and health care services are increasingly being delivered over the
      Internet. There is a strong argument that interventions delivered online should
      also be evaluated online to maximize the trial's external validity. Conducting a
      trial online can help reduce research costs and improve some aspects of internal
      validity. To date, there are relatively few trials of health interventions that
      have been conducted entirely online. In this paper we describe the major
      methodological issues that arise in trials (recruitment, randomization, fidelity
      of the intervention, retention, and data quality), consider how the online
      context affects these issues, and use our experience of one online trial
      evaluating an intervention to help hazardous drinkers drink less (DownYourDrink)
      to illustrate potential solutions. Further work is needed to develop online trial
      methodology.

PMID- 19403466
TI  - Adherence in internet interventions for anxiety and depression.
AB  - BACKGROUND: Open access websites which deliver cognitive and behavioral
      interventions for anxiety and depression are characterised by poor adherence. We
      need to understand more about adherence in order to maximize the impact of
      Internet-based interventions on the disease burden associated with common mental
      disorders. OBJECTIVE: The aims of this paper are to review briefly the adherence
      literature with respect to Internet interventions and to investigate the rates of
      dropout and compliance in randomized controlled trials of anxiety and depression
      Web studies. METHODS: A systematic review of randomized controlled trials using
      Internet interventions for anxiety and depression was conducted, and data was
      collected on dropout and adherence, predictors of adherence, and reasons for
      dropout. RESULTS: Relative to reported rates of dropout from open access sites,
      the present study found that the rates of attrition in randomized controlled
      trials were lower, ranging from approximately 1 - 50%. Predictors of adherence
      included disease severity, treatment length, and chronicity. Very few studies
      formally examined reasons for dropout, and most studies failed to use appropriate
      statistical techniques to analyze missing data. CONCLUSIONS: Dropout rates from
      randomized controlled trials of Web interventions are low relative to dropout
      from open access websites. The development of theoretical models of adherence is
      as important in the area of Internet intervention research as it is in the
      behavioral health literature. Disease-based factors in anxiety and depression
      need further investigation.

PMID- 19403467
TI  - Acceptability of a personally controlled health record in a community-based
      setting: implications for policy and design.
AB  - BACKGROUND: Consumer-centered health information systems that address problems
      related to fragmented health records and disengaged and disempowered patients are
      needed, as are information systems that support public health monitoring and
      research. Personally controlled health records (PCHRs) represent one response to
      these needs. PCHRs are a special class of personal health records (PHRs)
      distinguished by the extent to which users control record access and contents.
      Recently launched PCHR platforms include Google Health, Microsoft's HealthVault,
      and the Dossia platform, based on Indivo. OBJECTIVE: To understand the
      acceptability, early impacts, policy, and design requirements of PCHRs in a
      community-based setting. METHODS: Observational and narrative data relating to
      acceptability, adoption, and use of a personally controlled health record were
      collected and analyzed within a formative evaluation of a PCHR demonstration.
      Subjects were affiliates of a managed care organization run by an urban
      university in the northeastern United States. Data were collected using focus
      groups, semi-structured individual interviews, and content review of email
      communications. Subjects included: n = 20 administrators, clinicians, and
      institutional stakeholders who participated in pre-deployment group or individual
      interviews; n = 52 community members who participated in usability testing and/or
      pre-deployment piloting; and n = 250 subjects who participated in the full
      demonstration of which n = 81 initiated email communications to troubleshoot
      problems or provide feedback. All data were formatted as narrative text and coded
      thematically by two independent analysts using a shared rubric of a priori
      defined major codes. Sub-themes were identified by analysts using an iterative
      inductive process. Themes were reviewed within and across research activities
      (ie, focus group, usability testing, email content review) and triangulated to
      identify patterns. RESULTS: Low levels of familiarity with PCHRs were found as
      were high expectations for capabilities of nascent systems. Perceived value for
      PCHRs was highest around abilities to co-locate, view, update, and share health
      information with providers. Expectations were lowest for opportunities to
      participate in research. Early adopters perceived that PCHR benefits outweighed
      perceived risks, including those related to inadvertent or intentional
      information disclosure. Barriers and facilitators at institutional,
      interpersonal, and individual levels were identified. Endorsement of a dynamic
      platform model PCHR was evidenced by preferences for embedded searching, linking,
      and messaging capabilities in PCHRs; by high expectations for within-system
      tailored communications; and by expectation of linkages between self-report and
      clinical data. CONCLUSIONS: Low levels of awareness/preparedness and high
      expectations for PCHRs exist as a potentially problematic pairing. Educational
      and technical assistance for lay users and providers are critical to meet
      challenges related to: access to PCHRs, especially among older cohorts; workflow
      demands and resistance to change among providers; inadequate health and
      technology literacy; clarification of boundaries and responsibility for ensuring
      accuracy and integrity of health information across distributed data systems; and
      understanding confidentiality and privacy risks. Continued demonstration and
      evaluation of PCHRs is essential to advancing their use.

PMID- 19403468
TI  - Controlled clinical trial of zolpidem for the treatment of insomnia associated
      with attention-deficit/ hyperactivity disorder in children 6 to 17 years of age.
AB  - OBJECTIVE: The goal was to evaluate the hypnotic efficacy of zolpidem at 0.25
      mg/kg per day (maximum of 10 mg/day), compared with placebo, in children 6
      through 17 years of age who were experiencing insomnia associated with attention
      deficit/hyperactivity disorder. METHODS: An 8-week, North American, multicenter,
      double-blind, placebo-controlled, parallel-group study was conducted. Patients
      underwent stratification according to age (6-11 years [N = 111] or 12-17 years [N
      = 90]) and were assigned randomly to receive treatment with the study drug or
      placebo (in a 2:1 ratio). The primary efficacy variable was latency to persistent
      sleep between weeks 3 and 6. Secondary efficacy variables also were assessed, and
      behavioral and cognitive components of attention-deficit/hyperactivity disorder
      were monitored. Safety was assessed on the basis of reports of adverse events,
      abnormal laboratory data, vital signs, and physical examination findings. The
      potential for next-day residual effects also was assessed. RESULTS: The baseline
      adjusted mean change in latency to persistent sleep at week 4 did not differ
      significantly between the zolpidem and placebo groups (-20.28 vs -21.27 minutes).
      However, differences favoring zolpidem were observed for the older age group in
      Clinical Global Impression scores at weeks 4 and 8. No next-day residual effects
      of treatment were associated with zolpidem, and no rebound phenomena occurred
      after treatment discontinuation. Central nervous system and psychiatric disorders
      were the most-frequent treatment-emergent adverse events (>5%) that were observed
      more frequently with zolpidem than with placebo; these included dizziness,
      headache, and hallucinations. Ten (7.4%) patients discontinued zolpidem treatment
      because of adverse events. CONCLUSION: Zolpidem at a dose of 0.25 mg/kg per day
      to a maximum of 10 mg failed to reduce the latency to persistent sleep on
      polysomnographic recordings after 4 weeks of treatment in children and
      adolescents 6 through 17 years of age who had attention-deficit/hyperactivity
      disorder-associated insomnia.

PMID- 19403469
TI  - Pediatricians' perceptions of and preferred timing for pediatric palliative care.
AB  - OBJECTIVES: This study investigates how pediatricians define palliative care and
      their preferences regarding the timing of referrals for children with life
      limiting diseases. METHODS: A random sample of 800 pediatricians in Florida and
      California received mail and online surveys. Analyses included descriptive and
      multivariate regression analyses. RESULTS: Of all respondents (N = 303), 49.1%
      were female, 34.0% had been practicing for > or =20 years, 44.2% were members of
      a racial/ethnic minority, and 76.2% were in private practice. Pediatricians were
      divided in their definitions of palliative care; 41.9% defined it as hospice
      care, 31.9% offered alternative definitions, and 26.2% did not know. Although
      pediatricians overwhelmingly cited the need for many types of palliative care
      services, only 49.3% had ever referred patients to palliative care and 29.4% did
      not know whether local services existed. For 13 diseases that vary in life
      limitation, there was no consensus regarding the timing of referrals. Diversity
      across diseases predicted the most variation in referrals, whereas pediatrician
      characteristics did not. CONCLUSIONS: Despite recommendations to refer children
      to palliative care early in the course of illness, most pediatricians define
      palliative care as similar to hospice care and refer patients once curative
      therapy is no longer an option. Creating a more-practical definition of care, one
      that emphasizes an array of services throughout the course of an illness, as
      opposed to hospice care, may increase earlier palliative care referrals for
      children with life-limiting illnesses.

PMID- 19403471
TI  - Seven-year experience with a surveillance program to reduce methicillin-resistant
      Staphylococcus aureus colonization in a neonatal intensive care unit.
AB  - OBJECTIVES: The objectives of this study were to determine the incidence rates of
      neonatal methicillin-resistant Staphylococcus aureus colonization and infection
      after the implementation of a NICU methicillin-resistant S aureus surveillance
      and isolation program and to describe the characteristics of infants with
      methicillin-resistant S aureus colonization and invasive disease. METHODS: From
      August 2000 through August 2007, all infants admitted to the study NICU were
      screened for methicillin-resistant S aureus colonization with weekly nasal/rectal
      swabs; colonized or infected infants were isolated and cared for as a cohort. The
      annual incidence rates of methicillin-resistant S aureus colonization and
      infection were monitored, and characteristics of methicillin-resistant S aureus
      colonized and -infected infants were compared. Data were collected from infant,
      maternal, and hospital laboratory records. RESULTS: During the study period, 7997
      infants were admitted to the NICU and 102 methicillin-resistant S aureus
      colonized or -infected infants (1.3%) were identified. The incidence of
      methicillin-resistant S aureus decreased progressively from 1.79 cases per 1000
      patient-days in 2000 to 0.15 cases per 1000 patient-days in 2005, but the
      incidence then increased to 1.26 cases per 1000 patient-days in 2007. Fifteen of
      the 102 case infants (14.7%) had invasive infections; no significant differences
      between infected and colonized infants were identified. Methicillin-resistant S
      aureus isolates with 14 different antibiograms were found during the study
      period. There was a shift from isolates predominantly likely to be hospital
      associated in 2000-2004 to those likely to be community-associated in 2006-2007.
      CONCLUSIONS: A continuous program of weekly methicillin-resistant S aureus
      surveillance cultures and isolation of affected infants was associated with a
      variable incidence of methicillin-resistant S aureus colonization over a 7-year
      study period. Methicillin-resistant S aureus was not eradicated from this
      tertiary-care NICU, and our data suggest that infants were colonized by multiple
      different methicillin-resistant S aureus strains during the study period.

PMID- 19403470
TI  - Recognition of a Kawasaki disease shock syndrome.
AB  - OBJECTIVE: We sought to define the characteristics that distinguish Kawasaki
      disease shock syndrome from hemodynamically normal Kawasaki disease. METHODS: We
      collected data prospectively for all patients with Kawasaki disease who were
      treated at a single institution during a 4-year period. We defined Kawasaki
      disease shock syndrome on the basis of systolic hypotension for age, a sustained
      decrease in systolic blood pressure from baseline of > or =20%, or clinical signs
      of poor perfusion. We compared clinical and laboratory features, coronary artery
      measurements, and responses to therapy and analyzed indices of ventricular
      systolic and diastolic function during acute and convalescent Kawasaki disease.
      RESULTS: Of 187 consecutive patients with Kawasaki disease, 13 (7%) met the
      definition for Kawasaki disease shock syndrome. All received fluid resuscitation,
      and 7 (54%) required vasoactive infusions. Compared with patients without shock,
      patients with Kawasaki disease shock syndrome were more often female and had
      larger proportions of bands, higher C-reactive protein concentrations, and lower
      hemoglobin concentrations and platelet counts. Evidence of consumptive
      coagulopathy was common in the Kawasaki disease shock syndrome group. Patients
      with Kawasaki disease shock syndrome more often had impaired left ventricular
      systolic function (ejection fraction of <54%: 4 of 13 patients [31%] vs 2 of 86
      patients [4%]), mitral regurgitation (5 of 13 patients [39%] vs 2 of 83 patients
      [2%]), coronary artery abnormalities (8 of 13 patients [62%] vs 20 of 86 patients
      [23%]), and intravenous immunoglobulin resistance (6 of 13 patients [46%] vs 32
      of 174 patients [18%]). Impairment of ventricular relaxation and compliance
      persisted among patients with Kawasaki disease shock syndrome after the
      resolution of other hemodynamic disturbances. CONCLUSIONS: Kawasaki disease shock
      syndrome is associated with more-severe laboratory markers of inflammation and
      greater risk of coronary artery abnormalities, mitral regurgitation, and
      prolonged myocardial dysfunction. These patients may be resistant to
      immunoglobulin therapy and require additional antiinflammatory treatment.

PMID- 19403472
TI  - Permanent bilateral sensory and neural hearing loss of children after neonatal
      intensive care because of extreme prematurity: a thirty-year study.
AB  - OBJECTIVE: We present population-based, childhood prevalence rates of and
      neonatal risk factors for permanent hearing loss among extremely premature
      infants. METHODS: By using an inception-cohort, longitudinal study design for
      1974-2003, we studied permanent hearing loss among 1279 survivors with
      gestational age of < or =28 weeks and birth weight of <1250 g (mortality rate:
      42.7%; lost to follow-up monitoring: 4.7%) Newborn hearing screening, performed
      by experienced pediatric audiologists, used click-evoked auditory brainstem
      response testing after 1975. Survivors underwent repeated behavioral audiologic
      testing and multidisciplinary follow-up monitoring. Permanent hearing loss was
      defined as mild/moderate (26-70 dB hearing level), severe/profound (71 to >90 dB
      hearing level), delayed-onset (diagnosed after previously normal hearing), or
      progressive (increase in loss of > or =15 dB hearing level). Permanent hearing
      loss rates were established at 3 years of age, with newborn, infant, and >5-year
      final hearing outcomes being recorded. Risk factors were compared for children
      with and without hearing loss, odds ratios were calculated, and prediction
      performance was determined through area under the curve analysis. RESULTS: Forty
      (3.1%) of 1279 survivors 3 years of age had permanent hearing loss and 24 (1.9%)
      had severe/profound loss, with no changes over time. Bilateral delayed-onset loss
      occurred for 4 children (10%) and progressive loss for 11 children (28%). One
      child had auditory neuropathy, and 29 (73%) had multiple disabilities. Prolonged
      oxygen use, gastrointestinal surgery, patent ductus arteriosus ligation, and low
      socioeconomic index yielded good prediction of permanent hearing loss; oxygen use
      was the most significant predictor of severe/profound loss. CONCLUSIONS:
      Permanent hearing loss remains an adverse outcome of extreme prematurity,
      complicated by significant delayed-onset and progressive loss. Prolonged
      supplemental oxygen use is a marker for predicting permanent hearing loss; this
      requires detailed analysis of the pathophysiologic features, to reduce the
      prevalence of permanent hearing loss.

PMID- 19403473
TI  - Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases
      disease severity.
AB  - OBJECTIVES: The goals were to determine the prevalence of community-acquired
      methicillin-resistant Staphylococcus aureus colonization in patients with atopic
      dermatitis and to determine whether suppression of S aureus growth with sodium
      hypochlorite (bleach) baths and intranasal mupirocin treatment improves eczema
      severity. METHODS: A randomized, investigator-blinded, placebo-controlled study
      was conducted with 31 patients, 6 months to 17 years of age, with moderate to
      severe atopic dermatitis and clinical signs of secondary bacterial infections.
      All patients received orally administered cephalexin for 14 days and were
      assigned randomly to receive intranasal mupirocin ointment treatment and sodium
      hypochlorite (bleach) baths (treatment arm) or intranasal petrolatum ointment
      treatment and plain water baths (placebo arm) for 3 months. The primary outcome
      measure was the Eczema Area and Severity Index score. RESULTS: The prevalence of
      community-acquired methicillin-resistant S aureus in our study (7.4% of our S
      aureus-positive skin cultures and 4% of our S aureus-positive nasal cultures) was
      much lower than that in the general population with cultures at Children's
      Memorial Hospital (75%-85%). Patients in the group that received both the dilute
      bleach baths and intranasal mupirocin treatment showed significantly greater mean
      reductions from baseline in Eczema Area and Severity Index scores, compared with
      the placebo group, at the 1-month and 3-month visits. The mean Eczema Area and
      Severity Index scores for the head and neck did not decrease for patients in the
      treatment group, whereas scores for other body sites (submerged in the dilute
      bleach baths) decreased at 1 and 3 months, in comparison with placebo-treated
      patients. CONCLUSIONS: Chronic use of dilute bleach baths with intermittent
      intranasal application of mupirocin ointment decreased the clinical severity of
      atopic dermatitis in patients with clinical signs of secondary bacterial
      infections. Patients with atopic dermatitis do not seem to have increased
      susceptibility to infection or colonization with resistant strains of S aureus.

PMID- 19403474
TI  - Neighborhood socioeconomic status and homicides among children in urban Canada.
AB  - OBJECTIVE: We sought to determine the influence of neighborhood income on
      homicides among children living in urban Canada. METHODS: Homicides among
      children <15 years of age living in any of Canada's census metropolitan areas in
      1996, 1997, or 1998 were identified on the basis of vital statistics death
      registration data, by using International Classification of Diseases, Ninth
      Revision codes. Deaths were assigned to census tracts through postal codes, and
      the tracts were then assigned to neighborhood income quintiles on the basis of
      the proportions of the population below the Statistics Canada low-income cutoff
      values. Census population counts and intercensal population interpolations were
      used to estimate person-years at risk for rate calculations. Interquintile rate
      ratios and 95% confidence intervals were calculated. Poisson regression was used
      to model the effects of neighborhood income quintiles on homicide rates, after
      adjustment for age. RESULTS: During the 3-year study period, there were 87
      homicides among children <15 years of age in Canada's census metropolitan areas
      (0.82 cases per 100,000; not statistically different according to gender). The
      age-adjusted relative risks for the lowest versus highest neighborhood income
      quintiles were 2.95 for all children <15 years of age and 3.39 for children <5
      years of age. CONCLUSION: Effective child homicide-prevention strategies should
      be focused on children <5 years of age living in low-income areas.

PMID- 19403475
TI  - Validity of reported varicella history as a marker for varicella zoster virus
      immunity among unvaccinated children, adolescents, and young adults in the post
      vaccine licensure era.
AB  - OBJECTIVES: We assessed the validity of reported varicella history as a marker
      for varicella zoster virus immunity among unvaccinated persons 1 to 29 years of
      age, and we examined varicella disease characteristics associated with varicella
      zoster virus immunity among those reporting positive histories. METHODS: We
      conducted a cross-sectional study at 7 community-based sites in Philadelphia,
      Pennsylvania, between June 2004 and May 2006 and recruited 1476 participants 1 to
      29 years of age who had not been vaccinated against varicella. Sensitivity,
      specificity, and positive predictive value were determined by comparing self
      reported or parent-reported varicella histories from a standardized study
      interview with varicella zoster virus immunoglobulin G serological results for
      each participant. We performed multivariate logistic regression analyses to
      determine which disease characteristics best predicted seropositivity. RESULTS:
      The sensitivity of reported varicella history was highest (81%-89%) among
      participants > or =10 years of age, whereas specificity was highest among
      participants 1 to 4 years of age (99%) and > or =20 years (88%). Reported
      varicella history was highly predictive of seropositivity (>95%) only among
      participants > or =15 years of age. For participants 10 to 14 years of age,
      parental reports of a generalized itchy rash with 1 of the following were highly
      predictive of seropositivity: varicella transmission to another household member
      or being raised in a household with no other children. Among participants < or =9
      years of age, no combination of disease characteristics was both highly
      predictive of seropositivity and common. CONCLUSIONS: The validity of reported
      varicella history varies according to age, and a reported history is no longer
      highly predictive of seropositivity among cohorts born since 1994 (participants <
      or =9 years of age). Universal varicella vaccination, regardless of history, for
      these children should be considered, as should simplified criteria for varicella
      zoster virus immunity among unvaccinated persons born before 1994.

PMID- 19403476
TI  - Prospective validation of a clinical prediction model for Lyme meningitis in
      children.
AB  - OBJECTIVE: Lyme meningitis is difficult to differentiate from other causes of
      aseptic meningitis in Lyme disease-endemic regions. Parenteral antibiotics are
      indicated for Lyme meningitis but not viral causes of aseptic meningitis. A
      clinical prediction model was developed to distinguish Lyme meningitis from other
      causes of aseptic meningitis. Our objective was to prospectively validate this
      model. METHODS: Children between 2 and 18 years of age presenting to Hasbro
      Children's Hospital from April through October of 2006 and 2007 were enrolled if
      a lumbar puncture for meningitis showed a cerebrospinal fluid white blood cell
      count of >8 cells per microL. Cerebrospinal fluid was sent for Lyme antibody
      testing. The probability of Lyme meningitis was calculated by using the
      percentage of cerebrospinal fluid mononuclear cells, duration of headache, and
      presence of cranial neuropathy by using the prediction model. Definite Lyme
      meningitis cases were defined as cerebrospinal fluid pleocytosis with (1)
      positive Lyme serology confirmed by immunoblot or (2) erythema migrans rash.
      Possible Lyme meningitis cases were defined as cerebrospinal fluid pleocytosis
      with positive cerebrospinal fluid Lyme antibody. Sensitivity, specificity, and
      likelihood ratios for definite and possible Lyme meningitis were determined by
      using 10% increments of calculated probability of Lyme meningitis. RESULTS: Fifty
      children were enrolled, including 14 children with definite Lyme meningitis, 6
      with possible Lyme meningitis, and 30 with aseptic meningitis. A calculated
      probability of <10% for Lyme meningitis had a negative likelihood ratio of 0.006
      for definite and possible Lyme meningitis cases. A calculated probability of >50%
      for Lyme meningitis had a positive likelihood ratio of 100 using these
      definitions. CONCLUSIONS: A clinical prediction model using the percentage of
      cerebrospinal fluid mononuclear cells, headache duration, and presence of cranial
      neuropathy can differentiate children with Lyme meningitis from children with
      aseptic meningitis. Our findings suggest categories of low (<10%), indeterminate
      (10%-50%), and high (>50%) probability of Lyme meningitis.

PMID- 19403477
TI  - Lyme carditis in children: presentation, predictive factors, and clinical course.
AB  - OBJECTIVES: We sought to identify predictive factors for Lyme carditis in
      children and to characterize the clinical course of these patients. METHODS: We
      reviewed all cases of early disseminated Lyme disease presenting to our
      institution from January 1994 through July 2008, and summarized the presentation
      and course of those patients with carditis. A case-control study was used to
      identify predictive factors for carditis. Controls were patients with early
      disseminated Lyme disease without carditis. RESULTS: Of 207 children with early
      disseminated Lyme disease, 33 (16%) had carditis, 14 (42%) of whom had advanced
      heart block, including 9 (27%) with complete heart block. The median time to
      recovery of sinus rhythm in these 14 patients was 3 days (range: 1-7 days), and
      none required a permanent pacemaker. Four (12%) of 33 patients with carditis had
      depressed ventricular systolic function, 3 (9%) of whom required mechanical
      ventilation, temporary pacing, and inotropic support. Complete resolution of
      rhythm disturbances and myocardial dysfunction occurred in 24 (89%) of 27
      patients for whom follow-up data were available. Most patients with carditis also
      had other systemic Lyme involvement. By using multivariate logistic regression
      analysis, we found that children >10 years of age, those with arthralgias, and
      those with cardiopulmonary symptoms were more likely to have carditis.
      CONCLUSIONS: The spectrum of presentation for children with Lyme carditis is
      broad, ranging from asymptomatic, first-degree heart block to fulminant
      myocarditis. Variable degrees of heart block are the most common manifestation
      and occasionally require temporary pacing. Transient myocardial dysfunction,
      although less common, can be life-threatening. Advanced heart block resolves
      within 1 week in most cases. In children with early disseminated Lyme disease,
      older age, arthralgias, and cardiopulmonary symptoms independently predict the
      presence of carditis.

PMID- 19403478
TI  - Maternal smoking during pregnancy and neonatal behavior: a large-scale community
      study.
AB  - OBJECTIVE: To investigate the influence of prospectively measured smoking during
      pregnancy on aspects of neonatal behavior in a large community sample. METHODS:
      Participants were mothers and infants from the Providence, Rhode Island, cohort
      of the National Collaborative Perinatal Project enrolled between 1960 and 1966.
      Mothers with pregnancy/medical complications and infants with medical
      complications and/or born premature or of low birth weight were excluded. The
      final sample included 962 mother-infant pairs, 23% of whom were black. Maternal
      smoking was measured prospectively at each prenatal visit. Neonatal behavior was
      assessed by using the Graham-Rosenblith Behavioral Examination of the Neonate.
      Items from the examination were reduced to 3 subscales: irritability, muscle
      tone, and response to respiratory challenge. RESULTS: Sixty-two percent of the
      sample reported smoking during pregnancy, with 24% of smokers reporting smoking 1
      pack per day or more. We found a significant influence of maternal smoking
      exposure (none, moderate/less than 1 pack per day, heavy/1 pack per day or more)
      on irritability and muscle tone in the neonate, with exposed infants showing
      greater irritability and hypertonicity. Effects remained significant after
      controlling for significant covariates: maternal socioeconomic status, age, and
      race and infant birth weight and age. Posthoc tests suggested particular effects
      of heavy smoking on increased infant irritability and both moderate and heavy
      smoking exposure on increased muscle tone. CONCLUSIONS: In a large community
      sample, exposure to maternal smoking was associated with increased irritability
      and hypertonicity in neonates. Exposure to maternal smoking did not influence
      neonatal response to respiratory challenge. This study is the largest-scale
      investigation to date of the effects of maternal smoking (heavy and moderate) on
      examiner-assessed neonatal behavior. Given the associations between both maternal
      smoking and infant irritability and later behavioral dysregulation, results have
      important implications for early identification and intervention with at-risk
      offspring.

PMID- 19403479
TI  - Short sleep duration and behavioral symptoms of attention-deficit/hyperactivity
      disorder in healthy 7- to 8-year-old children.
AB  - OBJECTIVE: It has been hypothesized that sleep deprivation may manifest in
      children as behavioral symptoms rather than as tiredness, but only a few studies
      have investigated this hypothesis. The objective of our study was to evaluate
      whether short sleep is associated with behavioral symptoms of attention
      deficit/hyperactivity disorder in 7- to 8-year-old children. METHODS: We
      performed a cross-sectional study of children born in 1998 in Helsinki, Finland.
      The participants included 280 (146 girls, 134 boys) children with a mean age of
      8.1 years (SD: 0.3; range: 7.4-8.8). Sleep quality was measured by using
      actigraphs. The Sleep Disturbance Scale for Children and the Attention
      Deficit/Hyperactivity Disorder Rating Scale IV were administered to parents.
      RESULTS: Children whose average sleep duration as measured by actigraphs was
      short (<10th percentile, ie, <7.7 hours) and had a higher
      hyperactivity/impulsivity score (9.7 vs 7.8 or 7.5) and a higher attention
      deficit/hyperactivity disorder total score (17.3 vs 14.5 or 13.1) but a similar
      inattention score (7.6 vs 6.7 or 5.6) compared with children sleeping 7.7 to 9.4
      hours or >9.4 hours. In multivariate statistical models, short sleep duration
      remained a statistically significant predictor of hyperactivity/impulsivity, and
      sleeping difficulties were associated with hyperactivity/impulsivity,
      inattention, and the total score. There were no significant interactions between
      short sleep and sleeping difficulties. CONCLUSIONS: Children's short sleep
      duration and sleeping difficulties increase the risk for behavioral symptoms of
      attention-deficit/hyperactivity disorder.

PMID- 19403481
TI  - Infant functional status: the timing of physiologic maturation of premature
      infants.
AB  - OBJECTIVE: To describe the maturation of physiologic milestones in preterm
      infants born between 24 and 32 weeks' gestational age. METHODS: We abstracted
      daily physiologic maturity information on 865 infants born at < or =32 weeks'
      gestation in the Northern California Kaiser Permanente Medical Care Program
      between 1998 and 2001. Data included ventilator and incubator settings, body
      temperature, apnea and bradycardia spells, use of methylxanthines, feeding
      method, and requirements for intravenous fluids. Multivariable quantile
      regression models identified risk factors associated with longer postmenstrual
      age to achieve various physiologic milestones, including time to full oral
      feeding, time to wean from supplemental heat, the last day with an apnea or
      bradycardia episode, the last day on methylxanthine medications, and the last day
      on supplemental oxygen. RESULTS: Most milestones were achieved between 34 and 36
      weeks' postmenstrual age, although there were wide variations between patients.
      In most cases, feeding and oxygen milestones were achieved last. For each
      milestone there was a monotonic relationship between birth gestational age and
      the median achievement postmenstrual age. However, bronchopulmonary dysplasia and
      necrotizing enterocolitis strongly influenced these results in infants of younger
      gestational age. CONCLUSIONS: This study provides epidemiologic data describing
      the achievement of basic physiologic milestones that influence the discharge of a
      premature infant. This work serves as an additional contribution in the
      development of algorithms to monitor the progress of neonates through their
      initial hospitalization and provides a reference population for future
      interventions to improve the physiologic maturation of prematurely born infants.

PMID- 19403480
TI  - CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development,
      genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2
      deletion syndrome: a comparison of immunologic and nonimmunologic phenotypic
      features.
AB  - OBJECTIVES: CHARGE (coloboma, heart defect, atresia choanae, retarded growth and
      development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome
      22q11.2 deletion syndrome are known to have significant clinical overlap
      including cardiac anomalies, ear abnormalities, hearing loss, developmental
      delay, renal abnormalities, and cleft palate. Immunodeficiency has been well
      documented in 22q11.2 deletion, but there has been limited recognition of this
      potentially serious complication in CHARGE syndrome. The goals of our study were
      to identify clinical features unique to CHARGE syndrome or 22q11.2 deletion and
      to describe the spectrum of immunodeficiency found in patients with CHARGE
      syndrome. METHODS: This study included 25 children diagnosed with CHARGE syndrome
      with positive CHD7 mutations through the Children's Hospital of Philadelphia
      genetics program. Clinical features and laboratory findings were reviewed
      retrospectively. We compared our findings to data available for a large cohort of
      patients with 22q11.2 deletion syndrome followed in our clinical genetics
      program. RESULTS: Features found more commonly in CHARGE syndrome included
      coloboma, choanal atresia, facial nerve palsy, tracheoesophageal fistula, and
      genital hypoplasia in boys. A high incidence of marked hypocalcemia was observed
      in our study group (72%). We found a spectrum of cell-mediated immunodeficiency
      in our study group, which ranged from lymphopenia (60%) to severe combined
      immunodeficiency (8%). Defects in humoral immunity were documented in 4 patients
      and included severe hypogammaglobulinemia with decreased T-cell numbers,
      transient hypogammaglobulinemia during infancy, and immunoglobulin A deficiency.
      CONCLUSIONS: The presence of coloboma, choanal atresia, facial nerve palsy,
      tracheoesophageal fistula, or genital hypoplasia in boys should alert the
      clinician to the possibility of CHARGE syndrome rather than the 22q11.2 deletion.
      Molecular testing for CHD7 mutations may help to confirm the diagnosis. In this
      study, significant hypocalcemia and lymphopenia occurred more frequently in
      patients with CHARGE syndrome than in those with 22q11.2 deletion syndrome. Early
      inclusion of immunologists to the multidisciplinary care team (as with 22q11.2
      deletion) may be of great benefit to affected patients.

PMID- 19403483
TI  - Neonatal blue-light phototherapy does not increase nevus count in 9-year-old
      children.
AB  - OBJECTIVE: One of the most important risk factors for melanoma is the number of
      acquired common and atypical nevi in childhood. The role played by neonatal blue
      light phototherapy in the increasing incidence of common and atypical melanocytic
      nevi in childhood or adolescence has been discussed recently with discordant
      results. PATIENTS AND METHODS: We designed a multicenter study to assess the
      effects of neonatal blue-light phototherapy on nevus count in a cohort of 9-year
      old children. We counted back and arm nevi as a function of size in 828 children
      included in a French photoprotection educational campaign. History of neonatal
      phototherapy, phototype, skin, hair and eye color, and sunburn were assessed
      through questionnaires to which both parents and children responded, and a nevus
      count was performed by trained nurses blinded to phototherapy history. RESULTS:
      Mean nevus count was 16.7 per child. Twenty-two percent of the children had
      received neonatal blue-light phototherapy. Neonatal phototherapy had no effect on
      the nevus count irrespective of nevi location, nevi size, or phototype of the
      children. A light phototype, skin, and hair color; blue/green eyes; and history
      of sunburn were closely correlated with an increase in nevus count. CONCLUSIONS:
      This study found no evidence for a major role of blue-light phototherapy on nevus
      count in 9-year-old children. It underlines the dominant effect of phototype
      characteristics and history of sunburn in childhood on the early development of
      melanocytic nevi.

PMID- 19403484
TI  - Short- and long-term outcomes of necrotizing enterocolitis in infants with
      congenital heart disease.
AB  - OBJECTIVE: Congenital heart disease is a significant risk factor for necrotizing
      enterocolitis in the term infant. We compared the short- and long-term
      necrotizing enterocolitis-specific outcomes of infants with congenital heart
      disease with those of neonates without congenital heart disease. PATIENTS AND
      METHODS: A retrospective study of 202 patients with necrotizing enterocolitis
      treated at our center from May 1999 to August 2007 was conducted. Infants with
      necrotizing enterocolitis were grouped according to the presence (n = 76) or
      absence (n = 126) of congenital heart disease. Demographic and necrotizing
      enterocolitis-specific outcomes were recorded. The groups were compared by
      nonparametric and chi(2) analyses. Univariate and multivariate odds ratios were
      determined for each outcome. RESULTS: The average birth weight and gestational
      age of the 2 groups were not significantly different. The initial necrotizing
      enterocolitis severity, as determined by Bell stage, was less for necrotizing
      enterocolitis subjects with congenital heart disease compared with those without
      congenital heart disease. When controlling for birth weight and gestational age,
      the congenital heart disease group had decreased risk of perforation, need for a
      bowel operation, strictures, need for a stoma, sepsis, and short bowel syndrome
      compared with the non-congenital heart disease group. Although not statistically
      significant, subjects with congenital heart disease had a trend toward decreased
      risk of death from necrotizing enterocolitis, recurrent necrotizing
      enterocolitis, and need for peritoneal drainage. CONCLUSIONS: Infants with
      congenital heart disease and necrotizing enterocolitis have decreased risk of
      major short- and long-term negative outcomes associated with necrotizing
      enterocolitis compared with neonates without congenital heart disease.
      Differences in initial severity, range of age at diagnosis, and prognoses between
      subjects with necrotizing enterocolitis with and without cardiac disease suggest
      that necrotizing enterocolitis in the cardiac patient is a distinct disease
      process and should be labeled cardiogenic necrotizing enterocolitis.

PMID- 19403485
TI  - Recent decline in age at breast development: the Copenhagen Puberty Study.
AB  - OBJECTIVE: Recent publications showing unexpectedly early breast development in
      American girls created debate worldwide. However, secular trend analyses are
      often limited by poor data comparability among studies performed by different
      researchers in different time periods and populations. Here we present new
      European data systematically collected from the same region and by 1 research
      group at the beginning and end of the recent 15-year period. METHODS: Girls (N =
      2095) aged 5.6 to 20.0 years were studied in 1991-1993 (1991 cohort; n = 1100)
      and 2006-2008 (2006 cohort; n = 995). All girls were evaluated by palpation of
      glandular breast, measurement of height and weight, and blood sampling (for
      estradiol, luteinizing hormone, and follicle-stimulating hormone). Age
      distribution at entering pubertal breast stages 2 through 5, pubic hair stages 2
      through 5, and menarche was estimated for the 2 cohorts. RESULTS: Onset of
      puberty, defined as mean estimated age at attainment of glandular breast tissue
      (Tanner breast stage 2+), occurred significantly earlier in the 2006 cohort
      (estimated mean age: 9.86 years) when compared with the 1991 cohort (estimated
      mean age: 10.88 years). The difference remained significant after adjustment for
      BMI. Estimated ages at menarche were 13.42 and 13.13 years in the 1991 and 2006
      cohorts, respectively. Serum follicle-stimulating hormone and luteinizing hormone
      did not differ between the 2 cohorts at any age interval, whereas significantly
      lower estradiol levels were found in 8- to 10-year-old girls from the 2006 cohort
      compared with similarly aged girls from the 1991 cohort. CONCLUSIONS: We found
      significantly earlier breast development among girls born more recently.
      Alterations in reproductive hormones and BMI did not explain these marked
      changes, which suggests that other factors yet to be identified may be involved.

PMID- 19403487
TI  - Biliary atresia screening: why, when, and how?

PMID- 19403482
TI  - Stability of neuromotor outcomes at 18 and 30 months of age after extremely low
      birth weight status.
AB  - BACKGROUND: Extremely low birth weight (< or =1000 g) children have increased
      rates of cerebral palsy and other abnormal neurologic findings. OBJECTIVE: To
      investigate the stability of neuromotor findings between 18 and 30 months'
      adjusted age in extremely low birth weight infants. METHODS. Seven hundred
      nineteen extremely low birth weight infants with assessments at 18 and 30 months'
      adjusted age were included in this analysis. At each visit a neurologic
      examination, the modified gross motor function classification system, and the
      Bayley Scales of Infant Development II were administered. Logistic regression
      models were constructed to assess neonatal factors and neuromotor function at 18
      months of age associated with stability in neuromotor function. RESULTS: Eighty
      four percent of the children had agreement in neurologic/motor function at both
      visits. However, classification changed from normal to abnormal in 6% and from
      abnormal to normal in 10%. Diagnosis of cerebral palsy was consistent for 91% of
      the children, and the gross motor function classification system score was
      consistent for 83%. In multivariate models, factors associated with decreased
      severity or absence of cerebral palsy diagnosis at 30 months of age were higher
      gestational age, no periventricular leukomalacia or severe intraventricular
      hemorrhage, and a gross motor function classification system score of 0 (normal)
      at the 18-month visit, whereas factors associated with a new cerebral palsy
      diagnosis at 30 months of age were postnatal steroid use, periventricular
      leukomalacia or severe intraventricular hemorrhage, a gross motor function
      classification system score of > or =1 at 18 months of age, and asymmetrical limb
      movement at 18 months of age. CONCLUSIONS: Stability of neurologic diagnosis in
      84% and cerebral palsy in 91% of the children is reassuring. However, for a
      significant percentage of children, the neurologic diagnosis changes between 18
      and 30 months of age. The diagnosis of cerebral palsy may be delayed in some
      infants until an older adjusted age.

PMID- 19403486
TI  - The future of health insurance for children with special health care needs.
AB  - CONTEXT: Because of their elevated need for services, health insurance is
      particularly important for children with special health care needs. In this
      article we assess how well the current system is meeting the insurance needs of
      children with special health care needs and how emerging trends in health
      insurance may affect their well-being. METHODS: We begin with a review of the
      evidence on the impact of health insurance on the health care experiences of
      children with special health care needs based on the peer-reviewed literature. We
      then assess how well the current system meets the needs of these children by
      using data from 2 editions of the National Survey of Children With Special Health
      Care Needs. Finally, we present an analysis of recent developments and emerging
      trends in the health insurance marketplace that may affect this population.
      RESULTS: Although a high proportion of children with special health care needs
      have insurance at any point in time, nearly 40% are either uninsured at least
      part of the year or have coverage that is inadequate. Recent expansions in public
      coverage, although offset in part by a contraction in employer-based coverage,
      have led to modest but significant reductions in the number of uninsured children
      with special health care needs. Emerging insurance products, including consumer
      directed health plans, may expose children with special health care needs and
      their families to greater financial risks. CONCLUSIONS: Health insurance coverage
      has the potential to secure access to needed care and improve the quality of life
      for these children while protecting their families from financially burdensome
      health care expenses. Continued vigilance and advocacy for children and youth
      with special health care needs are needed to ensure that these children have
      access to adequate coverage and that they fare well under health care reform.

PMID- 19403488
TI  - Strategies for the prevention of MP3-induced hearing loss among adolescents:
      expert opinions from a Delphi study.
AB  - OBJECTIVE: To identify parties involved in the prevention of MP3-induced hearing
      loss among adolescents and potentially effective prevention strategies and
      interventions. METHODS: Thirty experts in fields such as scientific research,
      medical practice, community health professions, education, youth work, music
      entertainment, and enforcement authorities participated in a qualitative,
      electronic, 3-round, Web-based Delphi study. RESULTS: Multiple parties involved
      in the prevention of MP3-induced hearing loss among adolescents were identified;
      the most relevant are the adolescents themselves, their parents, manufacturers of
      MP3 players and earphones, and the authorities. The experts did not expect that
      adolescents in general would perform the necessary protective behaviors to
      prevent MP3-induced hearing loss. Two environmental health protection measures
      were identified as both relevant and feasible to be implemented (ie, authorities
      encourage manufacturers to produce safer products, and public health campaigns
      will be held to improve knowledge of the risks of high-volume music, possible
      protective measures, and consequences of hearing loss). CONCLUSIONS: Authorities,
      the music industry in general, and especially manufacturers of MP3 players and
      earphones should recognize their responsibility and create a safer MP3-listening
      environment by taking measures to protect today's youth from the dangers of
      listening to high-volume music on MP3 players.

PMID- 19403489
TI  - Psychological distress, television viewing, and physical activity in children
      aged 4 to 12 years.
AB  - OBJECTIVES: Sedentary behavior and physical activity may be independent risk
      factors for psychological distress in adolescents, although there is no existing
      information for children. We examined the cross-sectional association between
      psychological distress, television and screen entertainment time, and physical
      activity levels among a representative sample of children aged 4 to 12 years from
      the 2003 Scottish Health Survey. METHODS: Participants were 1486 boys and girls
      (mean age: 8.5 +/- 2.3 years). Parents answered on behalf of children who were
      required to be present. The parents completed the Strengths and Difficulties
      Questionnaire and information on television and screen entertainment time,
      physical activity, and dietary intake of their children. RESULTS: An abnormally
      high Strengths and Difficulties Questionnaire total difficulties score (20-40)
      was found in 4.2% of the sample. Approximately 25% of the children were exposed
      to television and screen entertainment at least 3 hours/day. In general linear
      models, television and screen entertainment time per week and physical activity
      levels were independently associated with the Strengths and Difficulties
      Questionnaire total difficulties score after adjustment for age, gender, area
      deprivation level, single-parent status, medical conditions, and various dietary
      intake indicators. There was also an additive interaction effect showing that the
      combination of high television and screen entertainment time and low physical
      activity was associated with the highest Strengths and Difficulties Questionnaire
      score. Higher television and screen entertainment exposure (>2.7 hours/day) alone
      resulted in a 24% increase in the Strengths and Difficulties Questionnaire score
      in comparison with lower television and screen entertainment exposure (<1.6
      hours/day), although when combined with low physical activity this resulted in a
      46% increase. CONCLUSION: Higher levels of television and screen entertainment
      time and low physical activity levels interact to increase psychological distress
      in young children.

PMID- 19403490
TI  - A cluster of children with seizures caused by camphor poisoning.
AB  - BACKGROUND: Isolated cases of camphor-induced seizures have been reported in
      young children after gastrointestinal, dermal, and inhalation exposure. In 1982,
      after a series of unintentional ingestions of camphor products, the US Food and
      Drug Administration restricted the camphor content to <11% in some products
      intended for medicinal use. Camphor products intended for use as pesticides must
      be registered with the US Environmental Protection Agency. Still, many imported
      camphor-containing products fail to meet Food and Drug Administration and
      Environmental Protection Agency requirements for labeling and content. OBJECTIVE:
      To describe a cluster of cases of camphor-associated seizure activity resulting
      from the availability of imported camphor products in certain ethnic populations
      that use it as a natural remedy. METHODS: We present 3 cases of seizures
      associated with imported, illegally sold camphor in young children who presented
      to a large, urban children's hospital in Bronx, New York, during a 2-week period.
      RESULTS: The children's ages ranged from 15 to 36 months. Two children ingested
      camphor, and 1 child was exposed through repetitive rubbing of camphor on her
      skin. All 3 patients required pharmacologic intervention to terminate the
      seizures. One patient required bag-valve-mask ventilation for transient
      respiratory depression. All 3 patients had leukocytosis, and 2 patients had
      hyperglycemia. Exposure occurred as a result of using camphor for spiritual
      purposes, cold remedy, or pest control. After identification of these cases, the
      New York City Department of Health released a public health warning to keep
      camphor products away from children. Similar warnings were issued later by other
      state health departments. CONCLUSIONS: These cases highlight the toxicity
      associated with camphor usage in the community and that inappropriate use of
      illegally sold camphor products is an important public health issue. Camphor may
      be a common, yet unrecognized, source of seizures in children in certain ethnic
      populations that use it as a natural remedy. Efforts are needed to educate the
      communities about the hazards of using camphor products and to limit the illegal
      availability of these products.

PMID- 19403491
TI  - Positive association between attention-deficit/ hyperactivity disorder medication
      use and academic achievement during elementary school.
AB  - OBJECTIVE: Approximately 4.4 million (7.8%) children in the United States have
      been diagnosed with attention-deficit/hyperactivity disorder, and 56% of affected
      children take prescription medications to treat the disorder. Attention
      deficit/hyperactivity disorder is strongly linked with low academic achievement,
      but the association between medication use and academic achievement in school
      settings is largely unknown. Our objective was to determine if reported
      medication use for attention-deficit/hyperactivity disorder is positively
      associated with academic achievement during elementary school. METHOD: To
      estimate the association between reported medication use and standardized
      mathematics and reading achievement scores for a US sample of 594 children with
      attention-deficit/hyperactivity disorder, we used 5 survey waves between
      kindergarten and fifth grade from the nationally representative Early Childhood
      Longitudinal Study--Kindergarten Class of 1998-1999 to estimate a first
      differenced regression model, which controlled for time-invariant confounding
      variables. RESULTS: Medicated children had a mean mathematics score that was 2.9
      points higher than the mean score of unmedicated peers with attention
      deficit/hyperactivity disorder. Children who were medicated for a longer duration
      (at >2 waves) had a mean reading score that was 5.4 points higher than the mean
      score of unmedicated peers with attention-deficit/hyperactivity disorder. The
      medication-reading association was lower for children who had an individualized
      education program than for those without such educational accommodation.
      CONCLUSIONS: The finding of a positive association between medication use and
      standardized mathematics and reading test scores is important, given the high
      prevalence of attention-deficit/hyperactivity disorder and its association with
      low academic achievement. The 2.9-point mathematics and 5.4-point reading score
      differences are comparable with score gains of 0.19 and 0.29 school years,
      respectively, but these gains are insufficient to eliminate the test-score gap
      between children with attention-deficit/hyperactivity disorder and those without
      the disorder. Long-term trials are needed to better understand the relationship
      between medication use and academic achievement.

PMID- 19403492
TI  - Impact of age at Kasai operation on its results in late childhood and
      adolescence: a rational basis for biliary atresia screening.
AB  - BACKGROUND: Increased age at surgery has a negative impact on results of the
      Kasai operation for biliary atresia in infancy and early childhood. It remained
      unclear if an age threshold exists and if this effect persists with extended
      follow-up. In this study we examined the relationship between increased age at
      surgery and its results in adolescence. METHODS: All patients with biliary
      atresia who were living in France and born between 1986 and 2002 were included.
      Median follow-up in survivors was 7 years. RESULTS: Included in the study were
      743 patients with biliary atresia, 695 of whom underwent a Kasai operation; 2-, 5
      , 10-, and 15-year survival rates with native liver were 57.1%, 37.9%, 32.4%, and
      28.5%, respectively. Median age at Kasai operation was 60 days and was stable
      over the study period. Whatever the follow-up (2, 5, 10, or 15 years), survival
      rates with native liver decreased when age at surgery increased (< or =30, 31-45,
      46-60, 61-75, and 76-90 days). Accordingly, we estimated that if every patient
      with biliary atresia underwent the Kasai operation before 46 days of age, 5.7% of
      all liver transplantations performed annually in France in patients younger than
      16 years could be spared. CONCLUSIONS: Increased age at surgery had a progressive
      and sustained deleterious effect on the results of the Kasai operation until
      adolescence. These findings indicate a rational basis for biliary atresia
      screening to reduce the need for liver transplantations in infancy and childhood.

PMID- 19403493
TI  - Outcomes of child sleep problems over the school-transition period: Australian
      population longitudinal study.
AB  - BACKGROUND: Adequate sleep optimizes children's learning and behavior. However,
      the natural history and impact of sleep problems during school transition is
      unknown. OBJECTIVES: To determine (1) the natural history of sleep problems over
      the 2-year period spanning school entry and (2) associations of children's health
      related quality of life, language, behavior, learning, and cognition at ages 6.5
      to 7.5 years with (a) timing and (b) severity of sleep problems. METHODS: Data
      were drawn from the Longitudinal Study of Australian Children. Children were aged
      4 to 5 years at wave 1 and 6 to 7 years at wave 2. Parent-reported predictors
      included (1) timing (none, persistent, resolved, incident) of moderate/severe
      sleep problems over the 2 waves and (2) severity (none, mild, moderate/severe) of
      sleep problems at wave 2. Outcomes included parent-reported health-related
      quality of life and language, parent- and teacher-reported behavior, teacher
      reported learning, and directly assessed nonverbal (matrix reasoning) and verbal
      (receptive vocabulary) cognition. Linear regression, adjusted for child age,
      gender, and social demographic variables, was used to quantify associations of
      outcomes with sleep-problem timing and severity. RESULTS: Sleep data were
      available at both waves for 4460 (89.5%) children, of whom 22.6% (17.0% mild,
      5.7% moderate/severe) had sleep problems at wave 2. From wave 1, 2.9% persisted
      and 2.8% developed a moderate/severe problem, whereas 10.1% resolved. Compared
      with no sleep problems, persistent and incident sleep problems predicted poorest
      health-related quality of life, behavior, language, and learning scores, whereas
      resolving problems showed intermediate outcomes. These outcomes also showed a
      dose-response relationship with severity at wave 2, with effect sizes for
      moderate/severe sleep problems ranging from -0.25 to -1.04 SDs. Cognitive
      outcomes were unaffected. CONCLUSIONS: Sleep problems during school transition
      are common and associated with poorer child outcomes. Randomized, controlled
      trials could determine if population-based sleep interventions can reduce the
      prevalence and impact of sleep problems.

PMID- 19403494
TI  - Prenatal, perinatal, and neonatal factors associated with autism spectrum
      disorders.
AB  - OBJECTIVE: To investigate prenatal, perinatal, and neonatal risk factors for
      autism spectrum disorders by using participants identified through broad
      ascertainment and reliable classification methods. METHODS: The targeted
      population was 8-year-old children born in 1994 and residing in 1 of the 3 most
      populous counties in Utah who were identified as having an autism spectrum
      disorder on the basis of methodology used by the 2002 Autism and Developmental
      Disabilities Monitoring Network. Of those identified, 132 children (115 boys, 17
      girls) had birth certificate records available. Each child was matched by gender
      and birth year to 100 controls (11 500 boys, 1700 girls) from the birth
      certificate database in a nested case-control design. Birth certificate records
      of participants and controls were surveyed for 23 potentially pathologic
      prenatal, perinatal, and neonatal factors. RESULTS: The prenatal factors that
      occurred significantly more frequently among children with autism spectrum
      disorders were advanced maternal age and parity. Increased duration of education
      among mothers of children with autism spectrum disorders was small but
      statistically significant. Significant perinatal factors were breech presentation
      and primary cesarean delivery. When corrected for breech presentation, a known
      indication for cesarean delivery, the association between primary cesarean
      delivery and autism spectrum disorders was eliminated. There were no significant
      associations found between autism spectrum disorders and neonatal factors.
      CONCLUSIONS: In the absence of other complications suggesting fetal distress, the
      association between breech presentation and autism spectrum disorders in this
      study suggests a shared etiology rather than causal relationship. Additional
      investigation focused on both genetic and environmental factors that link these
      autism spectrum disorder risk factors individually or collectively is needed.

PMID- 19403495
TI  - More information, less understanding: a randomized study on consent issues in
      neonatal research.
AB  - BACKGROUND: Valid consent for research requires comprehensive and understandable
      information to be disclosed to participants. The way that information is shared
      varies, but regulatory bodies usually determine style. Some reports have
      suggested that although information may be all-inclusive, it does little to
      support understanding. OBJECTIVE: To explore the impact of various information
      sharing approaches on parents' understanding of a research study and the validity
      of their consent. METHODS: This was a randomized, controlled trial. Parents of
      immature but well infants admitted to a large tertiary NICU in Edinburgh,
      Scotland, were randomly assigned within 72 hours of their infant's admission to
      receive 1 of 2 information leaflets, with or without a standardized verbal
      explanation, for a hypothetical intensive care research study. The leaflets
      differed in length and in the amount of detail in which the study process, risks,
      benefits, and patient rights were described. A questionnaire was used to elicit
      understanding about the purpose of the research, design of the study, procedures
      involved, and the consent process. RESULTS: Forty-one parents participated in the
      study. Those who received the longer leaflet without verbal explanation gained
      only limited understanding of the purpose of the research. The procedures
      involved in the study were understood better by those who received the shorter
      leaflet. Issues relating to consent and study design were readily understood in
      all groups. Irrespective of documentation style, verbal explanation significantly
      improved understanding. Differences in understanding had little effect on whether
      a parent would enroll his or her infant into the study. CONCLUSIONS: Verbal
      explanation significantly enhances understanding of the research process for
      participants regardless of the style of written documentation. However, shorter
      written information may lead to better understanding than lengthy, more complex
      documentation.

PMID- 19403497
TI  - Intrauterine inflammation, neonatal sepsis, and chronic lung disease: a 13-year
      hospital cohort study.
AB  - OBJECTIVE To determine the impact of intrauterine inflammation of maternal
      (chorioamnionitis) and fetal (umbilical vasculitis) origin and neonatal sepsis on
      the development of neonatal chronic lung disease in preterm infants. METHODS:
      This study was conducted at Royal Prince Alfred Hospital in Sydney, Australia.
      All infants born at <30 weeks' gestation, admitted to the NICU, and surviving to
      36 weeks' corrected gestation during 1992-2004 were eligible. Infants with major
      congenital abnormalities and those without placental examination were excluded.
      Antenatal and perinatal data extracted from hospital databases were correlated
      with the independent, central neonatal database and diagnostic laboratory
      reports. Neonatal sepsis was categorized according to blood culture isolates into
      3 groups: coagulase-negative staphylococci, other bacteria, and Candida species.
      RESULTS: There were 798 eligible infants born during the study period, and 761
      (95.4%) had placental examination. The mean gestational age was 27.4 +/- 1.5
      weeks. Antenatal maternal steroids were given to 94.4%. Regression analysis
      showed that chorioamnionitis with umbilical vasculitis and increasing gestation
      were associated with reduced odds of chronic lung disease. Chorioamnionitis
      without umbilical vasculitis showed a trend to reduced odds of chronic lung
      disease. Birth weight at <3rd percentile and neonatal sepsis were associated with
      increased odds of chronic lung disease. CONCLUSIONS: A fetal inflammatory
      response is protective for chronic lung disease. Neonatal sepsis is strongly
      associated with chronic lung disease, and the infecting organism is important.
      Coagulase-negative staphylococcal infection confers a risk for chronic lung
      disease similar to that of other bacteremias. Candidemia confers the greatest
      risk of chronic lung disease.

PMID- 19403496
TI  - The forgotten learning disability: epidemiology of written-language disorder in a
      population-based birth cohort (1976-1982), Rochester, Minnesota.
AB  - OBJECTIVE: The aim of this study was to report the incidence rates and other
      epidemiologic characterizations of written-language disorder. There have been no
      epidemiologic studies on the incidence of written-language disorder in the United
      States, and the use of a population-based birth cohort, longitudinally followed,
      is the most powerful method for reaching this objective. METHODS: In this
      population-based, retrospective birth cohort study, subjects included 5718
      children born between 1976 and 1982 in Rochester, Minnesota, who remained in the
      community after 5 years of age. Records from all public and nonpublic schools,
      medical facilities, and private tutorial services were reviewed and results of
      all individually administered IQ and achievement tests, and extensive medical,
      educational, and socioeconomic information, were collected. The essential
      features of writing problems from the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision were included in our operationalized
      definition of written-language disorder. Written-language disorder incident cases
      were established by using research criteria based on 3 formulas (regression-based
      discrepancy, nonregression-based discrepancy, and low achievement). RESULTS:
      Cumulative incidence rates of written-language disorder varied from 6.9% to 14.7%
      depending on the formula. Boys were 2 to 3 times more likely to be affected than
      girls regardless of the formula. Among all written-language disorder cases (N =
      806), 25% (n = 203) had written-language disorder without a reading disability.
      Specifics of the writing problems were identified for 87% (n = 702) of written
      language disorder cases. CONCLUSIONS: In this population-based birth cohort of
      school-aged children, written-language disorder was at least as frequent as
      reading disabilities and significantly more frequent among boys than girls.

PMID- 19403498
TI  - Differential patterns of 27 cord blood immune biomarkers across gestational age.
AB  - OBJECTIVES: Inflammation has been associated with preterm delivery and adverse
      neonatal outcomes such as cerebral palsy and chronic lung disease. However, no
      study to date has simultaneously examined a wide range of inflammatory mediators
      and their relationship to gestational age. We sought to describe the distribution
      of immune biomarkers in cord blood across gestational age and to investigate the
      association between biomarker level patterns and preterm birth. PATIENTS AND
      METHODS: As part of a large-scale molecular epidemiological study of preterm
      birth conducted at Boston Medical Center, this study analyzed both clinical and
      biomarker data from 927 births. Twenty-seven biomarkers were simultaneously
      quantified by immunoassay. The associations between the quartiles of 27
      biomarkers and 3 gestational groups (< or =32, 33-36, and > or =37 weeks) were
      analyzed. Biomarkers found to be significant were further analyzed for dose
      response correlation with preterm birth by logistic regression, adjusted for
      pertinent demographic and clinical factors. RESULTS: The 27 biomarkers could be
      classified into 1 of 3 groups: (1) biomarkers increased in preterm birth
      (interleukin [IL]-2, IL-4, IL-5, IL-8, IL-10, monocyte chemoattractant protein 1,
      macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, soluble IL-6 receptor
      alpha, tumor necrosis factor alpha, soluble tumor necrosis factor receptor I, and
      TREM-1 [triggering receptor expressed on myeloid cells 1]); (2) biomarkers
      decreased in preterm birth (brain-derived neurotrophic factor, IL-1beta, IL-18,
      matrix metalloproteinase 9, and neurotrophin 3); and (3) biomarkers not
      associated with preterm birth (IL-6, IL-12, IL-17, granulocyte/macrophage colony
      stimulating factor, interferon gamma, macrophage migration inhibitory factor,
      neurotrophin 4, RANTES [regulated on activation, normal T-cell expressed and
      secreted], transforming growth factor beta, and tumor necrosis factor beta).
      CONCLUSIONS: Biomarkers have different directions of association with
      prematurity; for significant biomarkers, the strength of association increases
      with biomarker concentration. Our results provide important information that
      could be used to guide additional studies aimed at determining mechanisms that
      contribute to preterm birth.

PMID- 19403500
TI  - First-week protein and energy intakes are associated with 18-month developmental
      outcomes in extremely low birth weight infants.
AB  - OBJECTIVE: We sought to evaluate the association between early protein and energy
      intake and neurodevelopment and growth of extremely low birth weight (<1000 g)
      infants. STUDY DESIGN: Daily protein and energy intakes were collected by chart
      review for the first 4 weeks of life on 148 extremely low birth weight survivors.
      A total of 124 infants (84%) returned for evaluation at 18 months' corrected age.
      Bivariate analysis tested correlations between weekly protein or energy intakes
      and Bayley Mental Development Index, Psychomotor Development Index, or growth at
      18 months. Separate regression models evaluated contributions of protein (grams
      per kilogram per day) and energy intake (kilojoules per kilogram per day) to the
      Mental Development Index, Psychomotor Development Index, and growth, while
      controlling for known confounders. RESULTS: After adjusting for confounding
      variables, week 1 energy and protein intakes were each independently associated
      with the Mental Development Index. During week 1, every 42 kJ (10 kcal)/kg per
      day were associated with a 4.6-point increase in the Mental Development Index and
      each gram per kilogram per day in protein intake with an 8.2-point increase in
      the Mental Development Index; higher protein intake was also associated with
      lower likelihood of length <10th percentile. CONCLUSIONS: Increased first-week
      protein and energy intakes are associated with higher Mental Development Index
      scores and lower likelihood of length growth restrictions at 18 months in
      extremely low birth weight infants. Emphasis should be placed on providing more
      optimal protein and energy during this first week.

PMID- 19403499
TI  - Perinatal correlates of Ureaplasma urealyticum in placenta parenchyma of
      singleton pregnancies that end before 28 weeks of gestation.
AB  - OBJECTIVES: The purpose of this work was to examine the relationship between
      Ureaplasma urealyticum in the placenta and perinatal outcomes in extreme preterm
      deliveries and to explore the influence of bacteria coinfection on perinatal
      outcomes in U urealyticum-positive placentas. METHODS: Under sterile conditions,
      a piece of chorion from 866 singleton deliveries before 28 weeks' gestation was
      obtained and flash frozen. The tissue was later homogenized and cultured for
      Ureaplasma and bacteria. Placentas were also examined histologically. Maternal
      and neonatal data were obtained prospectively. Each infant had 3 sets of cranial
      ultrasound scans between days 1 to 4, 5 to 14, and between day 15 and 40th week
      postconceptional age. Cranial ultrasound findings were by consensus of 2 or 2 of
      3 sonologists. RESULTS: U urealyticum was recovered from 6% and bacteria from
      47%; 47% of placentas had no bacteria detectable. Sixty-seven percent of
      Ureaplasma-positive placentas also harbored bacteria. Placentas that harbored U
      urealyticum only were more likely than sterile placentas to be associated with a
      higher prevalence of preterm labor and preterm premature rupture of membranes, as
      well as umbilical cord, fetal vessel, membrane, and parenchymal inflammation and
      to predict intraventricular hemorrhage and echolucent brain lesions. Placentas
      that harbored U urealyticum only were similar to placentas that harbored bacteria
      only. Recovery of U urealyticum and bacteria from same placenta did not enhance
      the differences between placentas with U urealyticum alone and sterile placentas.
      Recovery of U urealyticum only was not associated with a higher risk of death
      before day 7 of life. CONCLUSIONS: The presence of U urealyticum in placental
      parenchyma before 28 weeks is associated with increased risk of preterm labor and
      delivery, higher risk of fetal and maternal inflammation, and increased risk of
      intraventricular hemorrhage and echolucent brain lesions but not of early
      neonatal death.

PMID- 19403501
TI  - In utero smoke exposure, glutathione S-transferase P1 haplotypes, and respiratory
      illness-related absence among schoolchildren.
AB  - BACKGROUND: The GSTP1 Ile105Val variant and secondhand tobacco smoke exposure
      have been independently associated with acute respiratory illness; however,
      susceptibility to in utero and secondhand tobacco smoke has yet to be examined in
      relation to variation across the GSTP1 locus. OBJECTIVE: The purpose of this work
      was to determine whether variation across the GSTP1 locus is associated with
      respiratory illness-related school absences and to determine whether this
      relationship varies by in utero and secondhand tobacco smoke exposure. METHODS:
      Tobacco smoke exposure status, incident respiratory-related school absence
      records, and DNA samples was ascertained for 1132 Hispanic and non-Hispanic white
      elementary school children as part of the Children's Health Study. RESULTS: Four
      GSTP1 single-nucleotide polymorphisms were selected that accounted for 93% of the
      variation across the locus. Individual single-nucleotide polymorphism analyses
      showed a protective effect for the minor alleles in single-nucleotide
      polymorphisms 1 (rs6591255), 3 (GSTP1 Ile105Val: rs1695), and 4 (rs749174) for
      respiratory illness. The haplotype, which includes a minor allele for single
      nucleotide polymorphisms 1, 3, and 4 (h1011), was associated with a decreased
      risk of respiratory illness. The protective effect of GSTP1 variants was lost
      among individuals exposed to in utero and secondhand tobacco smoke. CONCLUSIONS:
      A common GSTP1 haplotype, which includes the functional Ile105Val polymorphism,
      was associated with respiratory-related school absences. The protection afforded
      by this haplotype was lost in children exposed to involuntary tobacco smoke. The
      paradigm of loss of genetic protection among those exposed to tobacco smoke has
      clinical and public health implications that warrant broader consideration in
      research and practice.

PMID- 19403502
TI  - Numbers needed to treat with phototherapy according to American Academy of
      Pediatrics guidelines.
AB  - OBJECTIVES: Our aims were to estimate the efficacy of hospital phototherapy for
      neonatal jaundice and the number needed to treat to prevent one infant from
      reaching the exchange transfusion level. METHODS: From a cohort of 281 898
      infants weighing > or =2000 g born at > or =35 weeks' gestation at 12 Northern
      California Kaiser hospitals from 1995 to 2004, we identified 22 547 who had a
      "qualifying total serum bilirubin level" within 3 mg/dL of the American Academy
      of Pediatrics 2004 guideline phototherapy threshold. We used multiple logistic
      regression to estimate the efficacy of hospital phototherapy within 8 hours at
      preventing the bilirubin level from exceeding the 2004 guideline's exchange
      transfusion threshold within 48 hours. We combined this efficacy estimate with
      other predictors of risk to estimate the numbers needed to treat at different
      values of covariates. RESULTS: Of the 22 547 eligible newborns, 5251 (23%)
      received hospital phototherapy within 8 hours of their qualifying bilirubin
      level. Only 354 (1.6%) ever exceeded the guideline exchange transfusion
      threshold; 187 (0.8%) did so within 48 hours. Among infants who did not have a
      positive direct antiglobulin test, hospital phototherapy within 8 hours was
      highly effective (adjusted odds ratio, 0.16; 95% confidence interval, 0.07-0.34).
      For infants with bilirubin levels 0-0.9 mg/dL above the phototherapy threshold,
      the estimated number needed to treat at mean values of covariates was 222 (95%
      CI: 107-502) for boys and 339 (95% CI: 154-729) for girls, ranging from 10 (95%
      CI: 6-19) for <24-hour-old, 36-week gestation boys to 3,041 (95% CI: 888-11 096)
      for > or =3-day-old 41-week girls. Hospital phototherapy was less effective for
      infants direct antiglobulin test-positive infants (adjusted odds ratio 0.55; 95%
      CI: 0.21-1.45; P = 0.01 for the direct antiglobulin test x phototherapy
      interaction). CONCLUSIONS: While hospital phototherapy is effective, the number
      needed to treat according to current guidelines varies considerably across
      different infant subgroups.

PMID- 19403504
TI  - Early systemic hypotension and vasopressor support in low birth weight infants:
      impact on neurodevelopment.
AB  - BACKGROUND: The duration and severity of systemic hypotension have been related
      with altered neurodevelopment. Cerebral circulation is pressure-passive in low
      birth weight infants with early systemic hypotension who receive cardiovascular
      support. The treatment of early systemic hypotension is controversial, because it
      has been associated with short-term and long-term morbidity in retrospective
      studies. However, there has been no prospective information on cardiovascular
      support for hypotension and morbidity. OBJECTIVE: Our goal for this prospective
      study was to evaluate the effect on neurodevelopment resulting from the use of
      vasopressors/inotropes for early systemic hypotension. METHODS: Low birth weight
      infants with early systemic hypotension (<24 hours of life; study group) were
      assigned randomly to receive dopamine (2.5-10 microg/kg per minute) or
      epinephrine (0.125-0.5 microg/kg per minute) in progressively larger doses until
      target blood pressure was attained (treatment-success subgroup). Hemodynamically
      stable patients who did not receive cardiovascular support were the control
      group. Outcome measures were serial cranial ultrasound up to 40 weeks, structured
      neurologic evaluation (every 3 months), and neurodevelopmental test at 2 to 3
      years of age. RESULTS: One hundred thirty patients were included (study = 60;
      treatment success = 38; controls = 70). Study-group patients had lower birth
      weight, gestational age, and 5-minute Apgar score, higher rates of premature
      rupture of membranes, need for cardiorespiratory resuscitation at birth, and
      sickness shortly after birth than the control group. The patients in the study
      group also had significantly higher serum troponin I levels at birth. Initial
      cranial ultrasound findings did not differ between groups, but the final cranial
      ultrasounds revealed higher rates of severe periventricular hemorrhage in the
      study group and higher rates of normal cranial ultrasounds in the control group.
      Only the latter remained when the treatment-success subgroup and control group
      were compared. Multivariate analysis did not detect any association between final
      cranial ultrasounds and the use of vasopressors/inotropes. Sixteen infants died
      and 103 were followed up (90% survival rate). No differences between groups were
      found in the rates of abnormal neurologic status, developmental delay, or
      combined adverse outcome (death or cerebral palsy or severe neurodevelopmental
      delay). CONCLUSIONS: Cautious use of cardiovascular support to treat early
      systemic hypotension in low birth weight infants seems to be safe. The question
      of whether raising systemic blood pressure to within a normal range will improve
      outcome should be examined by using appropriate study designs.

PMID- 19403503
TI  - Not just little adults: candidemia epidemiology, molecular characterization, and
      antifungal susceptibility in neonatal and pediatric patients.
AB  - OBJECTIVE: The purpose of this work was to identify differences in incidence,
      risk factors, microbiology, treatment, and clinical outcome of candidemia in
      neonates, children, and adults that might impact on management. PATIENTS AND
      METHODS: Cases of candidemia in Australia were identified prospectively by blood
      culture surveillance over 3 years. Episodes of candidemia in neonatal, pediatric,
      and adult age groups were analyzed and compared. RESULTS: Of 1005 incident cases,
      33 occurred in neonates, 110 in children, and 862 in adults. The respective
      annual age-specific incidences were 4.4, 0.9, and 1.8 per 100,000 population.
      Prematurity and ICU admission were major risk factors in neonates. Hematologic
      malignancy and neutropenia were significantly more frequent in children than in
      neonates and adults. Diabetes, renal disease, hemodialysis, and recent surgery
      were more common in adults. Candidemia was attributed to a vascular access device
      in 58% of neonates, 70% of children, and 44% of adults. Candida albicans caused
      approximately 48% of cases in all of the age groups. Candida parapsilosis was
      significantly more common in neonates and children (42% and 38% vs 15%). Candida
      glabrata was infrequent in neonates and children (9% and 3% vs 17%).
      Significantly more isolates from children were susceptible to fluconazole
      compared with those from adults (95% vs 75%). Fluconazole-resistant candidal
      isolates were infrequent in all of the age groups. Neonates and children were
      more likely to receive amphotericin B compared with adults. Adults were more
      likely to receive fluconazole. Survival rates at 30 days were 78% in neonates,
      90% in children, and 70% in adults. CONCLUSIONS: This study identifies
      significant differences in candidemia in neonates, children, and adults.
      Neonatologists and pediatricians must consider age-specific differences when
      interpreting adult studies and developing treatment and prevention guidelines.

PMID- 19403505
TI  - Long-term outcomes of restorative proctocolectomy in children with ulcerative
      colitis.
AB  - OBJECTIVE: Long-term outcomes of restorative proctocolectomy for pediatric-onset
      ulcerative colitis are unclear. METHODS: Questionnaires on health outcomes and
      quality of life were mailed to patients with childhood-onset ulcerative colitis
      who had undergone proctocolectomy with ileoanal anastomosis in 2 university
      hospitals between 1985 and 2005. Investigators not involved in the surgical
      management of the patients approached participants. Matched control children were
      randomly chosen from the Population Register Centre of Finland. RESULTS: Fifty
      two (66%) patients and 117 (37%) controls responded. After a mean follow-up of 10
      years, at least 1 surgical complication had occurred in 39 (75%) patients, and 28
      (54%) had undergone reoperation. Only 1 failure of ileoanal anastomosis occurred.
      Ulcerative colitis had been reclassified as Crohn disease in 6 (12%) patients.
      Pouchitis occurred in 37 (73%) patients. The median stool frequency was 5 for day
      and 1 for night, but 46% used medication to control stool frequency. Nighttime
      soiling was reported by 56% of the patients. The mean overall quality-of-life
      score, the mean BMI (22 kg/m(2) for both), and the number of subjects (aged >20
      years) with offspring (14% vs 15%) was similar to the population-based controls.
      CONCLUSIONS: Stool frequency after restorative proctocolectomy in children with
      ulcerative colitis is stable and comparable to those of adult patients. Although
      nighttime incontinence is common, general health status and overall quality of
      life are comparable to the normal population.

PMID- 19403507
TI  - Lyme disease: new thoughts and directions.

PMID- 19403508
TI  - Abusive head trauma in infants and children.
AB  - Shaken baby syndrome is a term often used by physicians and the public to
      describe abusive head trauma inflicted on infants and young children. Although
      the term is well known and has been used for a number of decades, advances in the
      understanding of the mechanisms and clinical spectrum of injury associated with
      abusive head trauma compel us to modify our terminology to keep pace with our
      understanding of pathologic mechanisms. Although shaking an infant has the
      potential to cause neurologic injury, blunt impact or a combination of shaking
      and blunt impact cause injury as well. Spinal cord injury and secondary hypoxic
      ischemic injury can contribute to poor outcomes of victims. The use of broad
      medical terminology that is inclusive of all mechanisms of injury, including
      shaking, is required. The American Academy of Pediatrics recommends that
      pediatricians develop skills in the recognition of signs and symptoms of abusive
      head injury, including those caused by both shaking and blunt impact, consult
      with pediatric subspecialists when necessary, and embrace a less mechanistic
      term, abusive head trauma, when describing an inflicted injury to the head and
      its contents.

PMID- 19403506
TI  - Clinical assessment and management of toddlers with suspected autism spectrum
      disorder: insights from studies of high-risk infants.
AB  - With increased public awareness of the early signs and recent American Academy of
      Pediatrics recommendations that all 18- and 24-month-olds be screened for autism
      spectrum disorders, there is an increasing need for diagnostic assessment of very
      young children. However, unique challenges exist in applying current diagnostic
      guidelines for autism spectrum disorders to children under the age of 2 years. In
      this article, we address challenges related to early detection, diagnosis, and
      treatment of autism spectrum disorders in this age group. We provide a
      comprehensive review of findings from recent studies on the early development of
      children with autism spectrum disorders, summarizing current knowledge on early
      signs of autism spectrum disorders, the screening properties of early detection
      tools, and current best practice for diagnostic assessment of autism spectrum
      disorders before 2 years of age. We also outline principles of effective
      intervention for children under the age of 2 with suspected/confirmed autism
      spectrum disorders. It is hoped that ongoing studies will provide an even
      stronger foundation for evidence-based diagnostic and intervention approaches for
      this critically important age group.

PMID- 19403511
TI  - Diagnostic imaging of child abuse.
AB  - The role of imaging in cases of child abuse is to identify the extent of physical
      injury when abuse is present and to elucidate all imaging findings that point to
      alternative diagnoses. Effective diagnostic imaging of child abuse rests on high
      quality technology as well as a full appreciation of the clinical and pathologic
      alterations occurring in abused children. This statement is a revision of the
      previous policy published in 2000.

PMID- 19403510
TI  - Safe transportation of preterm and low birth weight infants at hospital
      discharge.
AB  - Safe transportation of preterm and low birth weight infants requires special
      considerations. Both physiologic immaturity and low birth weight must be taken
      into account to properly position such infants. This clinical report provides
      guidelines for pediatricians and other caregivers who counsel parents of preterm
      and low birth weight infants about car safety seats.

PMID- 19403512
TI  - Cell-surface thiols affect cell entry of disulfide-conjugated peptides.
AB  - Cell-penetrating peptides (CPPs) can cross the cell membrane and are widely used
      to deliver bioactive cargoes inside cells. The cargo and the CPP are often
      conjugated through a disulfide bridge with the common acceptation that this
      linker is stable in the extracellular biological medium and should not perturb
      the internalization process. However, with the use of thiol-specific reagents
      combined with mass spectrometry (as a quantitative method to measure
      intracellular concentrations of peptides) and confocal microscopy (as a
      qualitative method to visualize internalized peptides) analyses, we could show
      that, depending on the peptide sequence, thiol/disulfide exchange reactions could
      happen at the cell surface. These exchange reactions lead to the reduction of
      disulfide conjugates. In addition, it was observed that not only disulfide- but
      also thiol-containing peptides could cross-react with cell-surface thiols. The
      peptides cross-linked by thiol-containing membrane proteins were either trapped
      in the membrane or further internalized. Therefore, a new route of cellular
      uptake was unveiled that is not restricted to CPPs: a protein kinase C peptide
      inhibitor that is not cell permeant could cross cell membranes when an activated
      cysteine (with a 3-nitro-2-pyridinesulfenyl moiety) was introduced in its
      sequence.

PMID- 19403513
TI  - Effects of erythropoietin in skin wound healing are dose related.
AB  - The hematopoietic growth factor erythropoietin (EPO) attracts attention due to
      its all-tissue-protective pleiotropic properties. We studied the effect of EPO on
      dermal regeneration using intravital microscopy in a model of full dermal
      thickness wounds in the skin-fold chamber of hairless mice. Animals received
      repetitive low doses or high doses of EPO (RLD-EPO or RHD-EPO) or a single high
      dose of EPO (SHD-EPO). SHD-EPO accelerated wound epithelialization, reduced wound
      cellularity, and induced maturation of newly formed microvascular networks. In
      contrast, RHD-EPO impaired the healing process, as indicated by delayed
      epithelialization, high wound cellularity, and lack of maturation of
      microvascular networks. Also, RHD-EPO caused an excessive erythrocyte mass and
      rheological malfunction, further deteriorating vessel and tissue maturation.
      Moreover, RHD-EPO altered fibroblast and keratinocyte migration in vitro, while
      both cell types exposed to RLD-EPO, and, in particular, to SHD-EPO showed
      accelerated wound scratch closure. In summary, our data show that a single
      application of a high dose of EPO accelerates and improves skin wound healing.

PMID- 19403514
TI  - Point of care testing in acute coronary syndromes: when and how?

PMID- 19403515
TI  - Proteomic characterisation of pancreatic islet beta-cells stimulated with
      pancreatic carcinoma cell conditioned medium.
AB  - AIM: To characterise the protein expression profiles of pancreatic islet beta
      cells affected by cancer cells, and to identify the potential islet molecules
      related to pancreatic cancer-associated diabetes. METHODS: The cellular proteins
      of islet beta-cell line INS-1 in response to conditioned medium (CM) prepared
      from pancreatic cancer cells were analysed using fluorescence-labelled 2D gel
      based proteomics (2D-DIGE). RESULTS: 10 proteins were over-expressed and five
      were under-expressed in cancer CM-stimulated beta-cells. Five differently
      expressed proteins were selected for further validation by Western blot analysis.
      HSP60 and peripherin, which have previously been reported to be associated with
      type 1 diabetes, and Prp19, a DNA repair protein, were up-regulated in INS-1
      cells after cancer cell CM stimulation; HMOX1 and GRP78 were down-regulated. The
      islets adjacent to human pancreatic carcinomas showed increased peripherin
      expression than normal pancreatic islets. CONCLUSION: These results provide new
      information regarding the regulation of protein expression in pancreatic cancer
      associated diabetes.

PMID- 19403516
TI  - Ankylosing spondylitis: a risk factor for myocardial infarction?
AB  - OBJECTIVE: To ascertain the prevalence of myocardial infarction (MI) in
      ankylosing spondylitis (AS) relative to that in the general population. METHODS:
      A questionnaire was sent to 593 patients with AS, aged between 50 and 75 years
      and registered at the Jan van Breemen Institute or VU University Medical Centre.
      A total of 383 (65%) patients with AS returned their questionnaire that covered
      the primary outcome, (non-fatal) MI. The prevalence of MI was calculated with
      data from the general population provided by Netherlands Information Network of
      General Practice databases as reference. RESULTS: The overall prevalence for MI
      was 4.4% in patients with AS versus 1.2% in the general population, resulting in
      an age- and gender-adjusted odds ratio of 3.1 (95% CI 1.9 to 5.1) for patients
      with AS. When non-responders (35%) were considered as non-MI the odds ratio
      decreased to 1.9 (95% CI 1.2 to 3.2). CONCLUSIONS: These observations indicate
      that the prevalence of MI is increased in patients with AS.

PMID- 19403517
TI  - Fixed-diameter scan protocol preferable for retinal nerve fibre layer measurement
      by optical coherence tomography in all sizes of optic discs.
AB  - BACKGROUND: Retinal nerve fibre layer (RNFL) measurements using a fixed-diameter
      versus a user-defined scan-protocol of optical coherence tomography (Stratus OCT)
      were compared in 32 normal, 62 glaucoma suspects and 36 glaucomatous eyes.
      METHODS: Peripapillary RNFL thickness was measured using the standard "fast" RNFL
      scan-protocol and proportional 2.27 x disc scan protocol. Disc size was measured
      using the "fast" optic disc protocol. The correlation between RNFL thickness for
      each scan-protocol and disc size was analysed. RESULTS: In normal eyes, RNFL
      thickness was independent of the optic-disc area using the fixed-diameter
      protocol (p = 0.92) but was inversely proportional to disc size using the
      proportional protocol (p<0.001). In glaucoma suspects, the optic-disc area
      correlated with RNFL thickness using the fixed-diameter protocol (p<0.001). In
      the multivariate analysis in glaucomatous eyes, the RNFL thickness using the
      fixed-diameter protocol was significantly affected by the mean deviation on
      visual fields but not by disc area (p<0.001 and p = 0.64 respectively)
      CONCLUSION: In normal subjects, disc size does not appear to affect RNFL
      measurements by OCT using the fixed-diameter protocol, thus indicating that RNFL
      thickness may be related to distance from the centre of the optic disc rather
      than the margin. The thicker RNFL observed in large glaucomatous discs in this
      study may be related to the earlier stage of glaucoma, though it may not apply to
      the general population.

PMID- 19403518
TI  - Characterisation of severe rod-cone dystrophy in a consanguineous family with a
      splice site mutation in the MERTK gene.
AB  - AIM: To characterise the ocular phenotype of a family segregating the splice site
      mutation c.2189+1G>T in the tyrosine kinase receptor gene MERTK. METHODS: Five
      affected children of a consanguineous Moroccan family were investigated by
      ophthalmic examinations, including fundus photography, autofluorescence (FAF)
      imaging, optical coherence tomography (OCT), psychophysical and
      electrophysiological methods. RESULTS: Affected children were between 5 and 19
      years of age, allowing an estimation of disease progression. Electroretinography
      demonstrated loss of scotopic and photopic function in the first decade of life.
      Younger siblings showed drusen-like deposits with focal relatively increased FAF
      in the macular area. With increasing age, a yellowish lesion with relatively
      increased FAF and subsequent macular atrophy developed. Visual acuity
      deteriorated with age and ranged between 20/50 in the best eye of the youngest
      affected and 20/400 in the worst eye of the oldest affected sibling. Spectral
      domain OCT revealed debris-like material in the subneurosensory space.
      CONCLUSION: The splice site mutation c.2189+1G>T in MERTK causes rod-cone
      dystrophy with a distinct macular phenotype. The debris in the subneurosensory
      space resembles that in the Royal College of Surgeons (RCS) rat being the mertk
      animal model. Patients might therefore benefit from advances in gene therapy that
      were previously achieved in the RCS rat.

PMID- 19403519
TI  - Short-term response of macular oedema to intravitreal bevacizumab.
AB  - BACKGROUND/AIMS: Bevacizumab has been shown to be an effective treatment of
      macular oedema. This study assesses the response of macular oedema to bevacizumab
      with specific focus on the first 24 h postinjection. METHODS: Subjects with
      diabetic macular oedema (DMO) or exudative age-related macular degeneration
      (ARMD) received intravitreal bevacizumab injections. Early Treatment of Diabetic
      Retinopathy Study (ETDRS) visual acuity and OCT macular thickness measurements
      were obtained at baseline, 1, 3, 6, 24 and 48 h, 1 week and 1 month
      postinjection. RESULTS: The average baseline OCT was 452.91 microm (SD 182.96,
      range 249.00 to 784.00). After injection, there was a statistically significant
      decrease in OCT thickness within 2 h with a plateau phase out to 24 h, followed
      by a significant drop between 24 and 48 h, and a return towards baseline between
      1 week and 1 month. Average changes in ETDRS visual acuity were not statistically
      significant, though many patients experienced a positive outcome. CONCLUSION:
      While there is an immediate pressure-related effect, it appears that the anti
      VEGF effects of bevacizumab require approximately 24 h to become active and
      persist for 2-3 weeks. These results suggest that injections at 2-3-week
      intervals might provide improved clinical outcomes, compared with the currently
      typical 4-6-week interval of injections.

PMID- 19403520
TI  - New tool for the simultaneous detection of 10 different genotypes of Acanthamoeba
      available from the American Type Culture Collection.
AB  - BACKGROUND: Acanthamoeba keratitis (AK) is a sight-threatening infection, and
      none of the current diagnosis tests are able to detect in one reaction low levels
      of the vast majority of strains associated with pathology. The goal of this work
      was to validate a new tool for the detection of the American Type Cell Collection
      (ATCC) referenced Acanthamoeba monitoring simultaneously DNA extraction yields
      and PCR inhibitors. Performances were assessed on corneal scrapings. METHODS:
      Primers were selected in a region bracketing a 41 591 bp of the A castellanii
      mitochondrion gene. DNA extraction and PCR inhibitors were monitored by adding an
      internal control (virus). Acanthamoeba were detected and quantified by the real
      time fast-duplex TaqMan PCR (f-d-real-t PCR) and negativity confirmed by SYBR
      Green real-time PCR. RESULTS: The f-d-real-t PCR detects 0.1 cyst/microl or less
      of the 10 referenced strains (sensitivity slightly lower for A astronyxis).
      Bacteria, fungi and herpesviruses do not cross-react. The specificity and
      sensitivity of the f-d-real-t PCR were higher than culture and other real-time
      PCR on 20 keratitis samples. CONCLUSION: The f-d-real t PCR detects in less than
      2 h the Acanthamoeba strains available from the ATCC with a higher sensitivity
      and specificity than techniques previously reported. Larger trials are necessary
      to validate its usefulness for disease management and environmental studies.

PMID- 19403521
TI  - Absence of Protein C Sapporo in Indian Patients With Venous Thrombosis.

PMID- 19403522
TI  - Live imaging of chloroplast FtsZ1 filaments, rings, spirals, and motile dot
      structures in the AtMinE1 mutant and overexpressor of Arabidopsis thaliana.
AB  - Chloroplast division involves the tubulin-related GTPase FtsZ that assembles into
      a ring structure (Z-ring) at the mid-chloroplast division site, which is where
      invagination and constriction of the envelope membranes occur. Z-ring assembly is
      usually confined to the mid-chloroplast site by a well balanced counteraction of
      the stromal proteins MinD and MinE. The in vivo mechanisms by which FtsZ
      nucleates at specific sites, polymerises into a protofilament and organizes a
      closed ring of filament bundles remain largely unknown. To clarify the dynamic
      aspects of FtsZ, we developed a living cell system for simultaneous visualisation
      of various FtsZ configurations, utilising the Arabidopsis thaliana overexpressor
      and mutant of the MinE (AtMinE1) gene, which were modified to weakly express
      green fluorescent protein (GFP) fused to AtFtsZ1-1. Time-lapse observation in the
      chloroplasts of both plants revealed disorderly movement of the dots and short
      filaments of FtsZ. The short filaments often appeared to emanate from the dots
      and to converge with a long filament, producing a thick cable. In the AtMinE1
      overexpressor, we also observed spirals along the longitudinal axis of the
      organelle that often rolled the closed rings together. In the atminE1 mutant, we
      visualised the 'isolated' rings with a maximum diameter of approximately 2 mum
      that did not encircle the organelle periphery, but appeared to be suspended in
      the stroma. Our observations further demonstrated heterogeneity in chloroplast
      shapes and concurrently altered configurations of FtsZ in the mutant.

PMID- 19403523
TI  - Dynamically driven ligand selectivity in cyclic nucleotide binding domains.
AB  - One of the mechanisms that minimize the aberrant cross-talk between cAMP- and
      cGMP-dependent signaling pathways relies on the selectivity of cAMP binding
      domains (CBDs). For instance, the CBDs of two critical eukaryotic cAMP receptors,
      i.e. protein kinase A (PKA) and the exchange protein activated by cAMP (EPAC),
      are both selectively activated by cAMP. However, the mechanisms underlying their
      cAMP versus cGMP selectivity are quite distinct. In PKA this selectivity is
      controlled mainly at the level of ligand affinity, whereas in EPAC it is mostly
      determined at the level of allostery. Currently, the molecular basis for these
      different selectivity mechanisms is not fully understood. We have therefore
      comparatively analyzed by NMR the cGMP-bound states of the essential CBDs of PKA
      and EPAC, revealing key differences between them. Specifically, cGMP binds PKA
      preserving the same syn base orientation as cAMP at the price of local steric
      clashes, which lead to a reduced affinity for cGMP. Unlike PKA, cGMP is
      recognized by EPAC in an anti conformation and generates several short and long
      range perturbations. Although these effects do not alter significantly the
      structure of the EPAC CBD investigated, remarkable differences in dynamics
      between the cAMP- and cGMP-bound states are detected for the ionic latch region.
      These observations suggest that one of the determinants of cGMP antagonism in
      EPAC is the modulation of the entropic control of inhibitory interactions and
      illustrate the pivotal role of allostery in determining signaling selectivity as
      a function of dynamic changes, even in the absence of significant affinity
      variations.

PMID- 19403524
TI  - Tissue transglutaminase is an essential participant in the epidermal growth
      factor-stimulated signaling pathway leading to cancer cell migration and
      invasion.
AB  - Epidermal growth factor (EGF) exerts pleiotropic effects during oncogenesis,
      including the stimulation of cell migration and invasiveness. Although a number
      of traditional signaling proteins (e.g. Ras and Rho GTPases) have been implicated
      in EGF-stimulated cancer cell migration, less is known about the identity of
      those proteins functioning further downstream in this growth factor pathway. Here
      we have used HeLa carcinoma cells as a model system for investigating the role of
      tissue transglutaminase (TGase), a protein that has been linked to oncogenesis,
      in EGF-stimulated cancer cell migration and invasion. Treatment of HeLa cells
      with EGF resulted in TGase activation and its accumulation at their leading
      edges, whereas knocking down TGase expression, or treating cells with a TGase
      inhibitor, blocked EGF-stimulated cell migration and invasion. We show that EGF
      signaling through Ras and c-Jun N-terminal kinase is responsible for targeting
      TGase to the leading edges of cells and activating it. The requirement for EGF to
      properly localize and activate TGase can be circumvented by the expression of
      oncogenic Ras (G12V), whose ability to stimulate migration is also dependent on
      TGase. We further show that, in the highly aggressive breast cancer cell line
      MDAMB231, where EGF stimulation is unnecessary for migration and invasive
      activity, TGase is already at the leading edge and activated. These findings
      demonstrate that TGase plays a key role in cancer cell motility and invasiveness
      and represents a previously unappreciated participant in the EGF pathway that
      stimulates these processes in cancer cells.

PMID- 19403527
TI  - Regulation of quinone oxidoreductase by the redox-sensing transcriptional
      regulator QorR in Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum cgR_1435 (cg1552) encodes a protein of the DUF24
      protein family, which is a novel family of transcriptional regulators. CgR1435
      (QorR) is a negative regulator of cgR_1436 (qor2), which is located upstream of
      cgR_1435 (qorR) in the opposite orientation, and its structural gene. QorR binds
      to the intergenic region between qor2 and qorR to repress their expression, which
      is induced by the thiol-specific oxidant diamide. The DNA-binding activity of
      QorR is impaired by oxidants such as diamide, H(2)O(2), and cumene hydroperoxide
      in vitro, and its lone cysteine residue (Cys-17) is essential for redox
      responsive regulation of QorR activity both in vivo and in vitro. Moreover, a
      disruptant of qor2, which is a homologue of the ytfG gene of Escherichia coli
      encoding quinone oxidoreductase, shows increased sensitivity to diamide. It is
      concluded that the redox-sensing transcriptional regulator QorR is involved in
      disulfide stress response of C. glutamicum by regulating qor2 expression.

PMID- 19403525
TI  - Thromboxane A2 receptor activates a Rho-associated kinase/LKB1/PTEN pathway to
      attenuate endothelium insulin signaling.
AB  - This study was conducted to elucidate the molecular mechanisms of thromboxane A2
      receptor (TP)-induced insulin resistance in endothelial cells. Exposure of human
      umbilical vein endothelial cells (HUVECs) or mouse aortic endothelial cells to
      either IBOP or U46619, two structurally related thromboxane A(2) mimetics,
      significantly reduced insulin-stimulated phosphorylation of endothelial nitric
      oxide synthase (eNOS) at Ser(1177) and Akt at Ser(473). These effects were
      abolished by pharmacological or genetic inhibitors of TP. TP-induced suppression
      of both eNOS and Akt phosphorylation was accompanied by up-regulation of PTEN
      (phosphatase and tension homolog deleted on chromosome 10), Ser(380)/Thr(382/383)
      PTEN phosphorylation, and PTEN lipid phosphatase activity. PTEN-specific small
      interference RNA restored insulin signaling in the face of TP activation. The
      small GTPase, Rho, was also activated by TP stimulation, and pretreatment of
      HUVECs with Y27632, a Rho-associated kinase inhibitor, rescued TP-impaired
      insulin signaling. Consistent with this result, pertussis toxin abrogated IBOP
      induced dephosphorylation of both Akt and eNOS, implicating the G(i) family of G
      proteins in the suppressive effects of TP. In mice, high fat diet-induced
      diabetes was associated with aortic PTEN up-regulation, PTEN
      Ser(380)/Thr(382/383) phosphorylation, and dephosphorylation of both Akt (at
      Ser(473)) and eNOS (at Ser(1177)). Importantly, administration of TP antagonist
      blocked these changes. We conclude that TP stimulation impairs insulin signaling
      in vascular endothelial cells by selectively activating the Rho/Rho-associated
      kinase/LKB1/PTEN pathway.

PMID- 19403528
TI  - A unique 2-sulfated {beta}-galactan from the egg jelly of the sea urchin
      Glyptocidaris crenularis: conformation flexibility versus induction of the sperm
      acrosome reaction.
AB  - Sulfated polysaccharides from the egg jelly of sea urchins act as species
      specific inducers of the sperm acrosome reaction, which is a rare molecular
      mechanism of carbohydrate-induced signal-transduction event in animal cells. The
      sea urchin polysaccharides differ in monosaccharide composition (l-fucose or l
      galactose), glycosylation, and sulfation sites, but they are always in the alpha
      anomeric configuration. Herein, structural analysis of the polysaccharide from
      the sea urchin Glyptocidaris crenularis surprisingly revealed a unique sulfated
      beta-d-galactan composed by (3-beta-d-Galp-2(OSO(3))-1-->3-beta-d-Galp-1)(n)
      repeating units. Subsequently, we used the G. crenularis galactan to compare
      different 2-sulfated polysaccharides as inducers of the acrosome reaction using
      homologous and heterologous sperm. We also tested the effect of chemically over
      sulfated galactans. Intriguingly, the anomeric configuration of the glycosidic
      linkage rather than the monosaccharide composition (galactose or fucose) is the
      preferential structural requirement for the effect of these polysaccharides on
      sea urchin fertilization. Nuclear magnetic resonance and molecular dynamics
      indicate that sulfated alpha-galactan or alpha-fucan have less dynamic structural
      behavior, exhibiting fewer conformational populations, with an almost exclusive
      conformational state with glycosidic dihedral angles Phi/Psi = -102 degrees /131
      degrees . The preponderant conformer observed in the sulfated alpha-galactan or
      alpha-fucan is not observed among populations in the beta-form despite its more
      flexible structure in solution. Possibly, a proper spatial arrangement is
      required for interaction of the sea urchin-sulfated polysaccharides with the
      specific sperm receptor.

PMID- 19403526
TI  - Differential inhibitor of Gbetagamma signaling to AKT and ERK derived from
      phosducin-like protein: effect on sphingosine 1-phosphate-induced endothelial
      cell migration and in vitro angiogenesis.
AB  - Differential inhibitors of Gbetagamma-effector regions are required to dissect
      the biological contribution of specific Gbetagamma-initiated signaling pathways.
      Here, we characterize PhLP-M1-G149, a Gbetagamma-interacting construct derived
      from phosducin-like protein 1 (PhLP) as a differential inhibitor of Gbetagamma,
      which, in endothelial cells, prevented sphingosine 1-phosphate-induced
      phosphorylation of AKT, glycogen synthase kinase 3beta, cell migration, and
      tubulogenesis, while having no effect on ERK phosphorylation or hepatocyte growth
      factor-dependent responses. This construct attenuated the recruitment of
      phosphoinositide 3-kinase gamma (PI3Kgamma) to the plasma membrane and the
      signaling to AKT in response to Gbetagamma overexpression. In
      coimmunoprecipitation experiments, PhLP-M1-G149 interfered with the interaction
      between PI3Kgamma and Gbetagamma. Other PhLP-derived constructs interacted with
      Gbetagamma but were not effective inhibitors of Gbetagamma signaling to AKT or
      ERK. Our results indicate that PhLP-M1-G149 is a suitable tool to differentially
      modulate the Gbetagamma-initiated pathway linking this heterodimer to AKT,
      endothelial cell migration, and in vitro angiogenesis. It can be also useful to
      further characterize the molecular determinants of the Gbetagamma-PI3Kgamma
      interaction.

PMID- 19403529
TI  - Coordinate regulation of glycan degradation and polysaccharide capsule
      biosynthesis by a prominent human gut symbiont.
AB  - Bacteria in the distal human gut have evolved diverse abilities to metabolize
      complex glycans, including the capacity to degrade these compounds as nutrients
      and to assemble their component sugars into new polymers such as extracellular
      capsules. The human gut bacterium Bacteroides thetaiotaomicron is well endowed
      with the ability to metabolize both host- and diet-derived glycans. Its genome
      contains 88 different polysaccharide utilization loci (PULs) for complex glycan
      catabolism and eight different gene clusters for capsular polysaccharide
      biosynthesis. Here, we investigate one of the prominent mechanisms by which this
      gut symbiont regulates many PULs involved in host mucin O-glycan degradation;
      namely, transcriptional regulation via the concerted interactions of cell
      envelope-localized TonB-dependent transporters, extra-cytoplasmic function sigma
      factors and anti-sigma factors, which participate together in a regulatory
      pathway termed trans-envelope signaling. Unexpectedly, we found that several
      different trans-envelope signaling switches involved in PUL-mediated O-glycan
      degradation also modulate capsular polysaccharide synthesis. A novel regulatory
      pathway, which is dependent on expression of O-glycan-targeting outer membrane
      proteins, governs this coordinated regulation of glycan catabolism and capsule
      synthesis. This latter finding provides a new link in the dynamic interplay
      between complex glycan metabolism, microbial physiology, and host responses that
      occurs during colonization of the gut.

PMID- 19403530
TI  - Cryoprotectant biosynthesis and the selective accumulation of threitol in the
      freeze-tolerant Alaskan beetle, Upis ceramboides.
AB  - Adult Upis ceramboides do not survive freezing in the summer but tolerate
      freezing to -60 degrees C in midwinter. The accumulation of two cryoprotective
      polyols, sorbitol and threitol, is integral to the extraordinary cold-hardiness
      of this beetle. U. ceramboides are the only animals known to accumulate high
      concentrations of threitol; however, the biosynthetic pathway has not been
      studied. A series of (13)C-labeled compounds was employed to investigate this
      biosynthetic pathway using (13)C{(1)H} NMR spectroscopy. In vivo metabolism of
      (13)C-labeled glucose isotopomers demonstrates that C-3-C-6 of glucose become C-1
      C-4 of threitol. This labeling pattern is expected for 4-carbon saccharides
      arising from the pentose phosphate pathway. In vitro experiments show that
      threitol is synthesized from erythrose 4-phosphate, a C(4) intermediate in the
      PPP. Erythrose 4-phosphate is epimerized and/or isomerized to threose 4
      phosphate, which is subsequently reduced by a NADPH-dependent polyol
      dehydrogenase and dephosphorylated by a sugar phosphatase to form threitol.
      Threitol 4-phosphate appears to be the preferred substrate of the sugar
      phosphatase(s), promoting threitol synthesis over that of erythritol. In
      contrast, the NADPH-dependent polyol dehydrogenase exhibits broad substrate
      specificity. Efficient erythritol catabolism under conditions that promote
      threitol synthesis, coupled with preferential threitol biosynthesis, appear to be
      responsible for the accumulation of high concentrations of threitol (250 mm)
      without concomitant accumulation of erythritol.

PMID- 19403531
TI  - The spider Harpactea sadistica: co-evolution of traumatic insemination and
      complex female genital morphology in spiders.
AB  - The males of invertebrates from a few phyla, including arthropods, have been
      reported to practise traumatic insemination (TI; i.e. injecting sperm by using
      the copulatory organ to penetrate the female's body wall). As all previously
      reported arthropod examples have been insects, there is considerable interest in
      whether TI might have evolved independently in other arthropods. The research
      reported here demonstrates the first case of TI in the arthropod subphylum
      Chelicerata, in particular how the genital morphology and mating behaviour of
      Harpactea sadistica (Rezac 2008), a spider from Israel, has become adapted
      specifically for reproduction based on TI. Males have needle-like intromittent
      organs and females have atrophied spermathecae. In other spiders, eggs are
      fertilized simultaneously with oviposition, but the eggs of H. sadistica are
      fertilized in the ovaries (internal fertilization) and develop as embryos before
      being laid. Sperm-storage organs of phylogenetically basal groups to H. sadistica
      provide males with last male sperm priority and allow removal of sperm by males
      that mate later, suggesting that TI might have evolved as an adaptive strategy to
      circumvent an unfavourable structure of the sperm-storage organs, allowing the
      first male to mate with paternity advantage. Understanding the functional
      significance of TI gives us insight into factors underlying the evolution of the
      genital and sperm-storage morphology in spiders.

PMID- 19403532
TI  - A new Homo erectus (Zhoukoudian V) brain endocast from China.
AB  - A new Homo erectus endocast, Zhoukoudian (ZKD) V, is assessed by comparing it
      with ZKD II, ZKD III, ZKD X, ZKD XI, ZKD XII, Hexian, Trinil II, Sambungmacan
      (Sm) 3, Sangiran 2, Sangiran 17, KNM-ER 3733, KNM-WT 15 000, Kabwe, Liujiang and
      31 modern Chinese. The endocast of ZKD V has an estimated endocranial volume of
      1140 ml. As the geological age of ZKD V is younger than the other ZKD H. erectus,
      evolutionary changes in brain morphology are evaluated. The brain size of the ZKD
      specimens increases slightly over time. Compared with the other ZKD endocasts,
      ZKD V shows important differences, including broader frontal and occipital lobes,
      some indication of fuller parietal lobes, and relatively large brain size that
      reflect significant trends documented in later hominin brain evolution. Bivariate
      and principal component analyses indicate that geographical variation does not
      characterize the ZKD, African and other Asian specimens. The ZKD endocasts share
      some common morphological and morphometric features with other H. erectus
      endocasts that distinguish them from Homo sapiens.

PMID- 19403533
TI  - Evolutional trends and palaeobiogeography of the Ordovician trilobite
      Ovalocephalus Koroleva 1959.
AB  - Ovalocephalus has a long stratigraphic range and wide geographical distribution
      in Ordovician peri-Gondwana. Based largely on the well-preserved specimens
      recently collected from China, all known forms are revised and listed.
      Phylogenetic analysis was conducted on the genus, involving 10 species. As
      suggested by the strict consensus tree, evolutional trends of the genus include
      mainly the isolation of the anterior glabellar portion anterior to S1, the
      forward shifting of eyes and the related lengthening (exsag.) of the posterior
      fixigena, the reduction of the number of pygidial axial segments and pleural
      abaxial rounded free tips, the shortening of the pygidial postaxial region, and
      the development of cranidial genal spines. Ovalocephalus may have originated in
      shallow-water sites of the South China Plate in the Early Floian, but migrated
      into the deep-water regions from the Darriwilian onwards. All the records of the
      genus from the Early Floian to Early Katian were confined to eastern peri
      Gondwanan plates and terranes in low-latitude zones. It was only restricted to
      the South China, Tarim and North China plates until the Middle Darriwilian, but
      the Late Darriwilian eustatic sea-level rise and especially the Sandbian-Early
      Katian immense transgression may have brought about its dispersal to Alborz,
      Sibumasu and central Asian terranes. Following the closure of the Tornquist Sea,
      the genus was even able to spread to Baltica during the latest Katian, and the
      pre-Hirnantian warming (the Boda event) may have promoted a wider distribution of
      Ovalocephalus to western peri-Gondwana (the Taurides and Armorica terranes) in
      the then-high latitudes.

PMID- 19403534
TI  - The scramble for Africa: pan-temperate elements on the African high mountains.
AB  - The composition of isolated floras has long been thought to be the result of
      relatively rare long-distance dispersal events. However, it has recently become
      apparent that the recruitment of lineages may be relatively easy and that many
      dispersal events from distant but suitable habitats have occurred, even at an
      infraspecific level. The evolution of the flora on the high mountains of Africa
      has been attributed to the recruitment of taxa not only from the African lowland
      flora or the Cape Floristic Region, but also to a large extent from other areas
      with temperate climates. We used the species rich, pan-temperate genera Carex,
      Ranunculus and Alchemilla to explore patterns in the number of recruitment events
      and region of origin. Molecular phylogenetic analyses, parametric bootstrapping
      and ancestral area optimizations under parsimony indicate that there has been a
      high number of colonization events of Carex and Ranunculus into Africa, but only
      two introductions of Alchemilla. Most of the colonization events have been
      derived from Holarctic ancestors. Backward dispersal out of Africa seems to be
      extremely rare. Thus, repeated colonization from the Northern Hemisphere in
      combination with in situ radiation has played an important role in the
      composition of the flora of African high mountains.

PMID- 19403535
TI  - Dinosaur diversity and the rock record.
AB  - Palaeobiodiversity analysis underpins macroevolutionary investigations, allowing
      identification of mass extinctions and adaptive radiations. However, recent large
      scale studies on marine invertebrates indicate that geological factors play a
      central role in moulding the shape of diversity curves and imply that many
      features of such curves represent sampling artefacts, rather than genuine
      evolutionary events. In order to test whether similar biases affect diversity
      estimates for terrestrial taxa, we compiled genus-richness estimates for three
      Mesozoic dinosaur clades (Ornithischia, Sauropodomorpha and Theropoda). Linear
      models of expected genus richness were constructed for each clade, using the
      number of dinosaur-bearing formations available through time as a proxy for the
      amount of fossiliferous rock outcrop. Modelled diversity estimates were then
      compared with observed patterns. Strong statistically robust correlations
      demonstrate that almost all aspects of ornithischian and theropod diversity
      curves can be explained by geological megabiases, whereas the sauropodomorph
      record diverges from modelled predictions and may be a stronger contender for
      identifying evolutionary signals. In contrast to other recent studies, we
      identify a marked decline in dinosaur genus richness during the closing stages of
      the Cretaceous Period, indicating that the clade decreased in diversity for
      several million years prior to the final extinction of non-avian dinosaurs at the
      Cretaceous-Palaeocene boundary.

PMID- 19403536
TI  - Arthropod visual predators in the early pelagic ecosystem: evidence from the
      Burgess Shale and Chengjiang biotas.
AB  - Exceptional fossil specimens with preserved soft parts from the Maotianshan Shale
      (ca 520 Myr ago) and the Burgess Shale (505 Myr ago) biotas indicate that the
      worldwide distributed bivalved arthropod Isoxys was probably a non-benthic visual
      predator. New lines of evidence come from the functional morphology of its
      powerful prehensile frontal appendages that, combined with large spherical eyes,
      are thought to have played a key role in the recognition and capture of swimming
      or epibenthic prey. The swimming and steering of this arthropod was achieved by
      the beating of multiple setose exopods and a flap-like telson. The appendage
      morphology of Isoxys indicates possible phylogenetical relationships with the
      megacheirans, a widespread group of assumed predator arthropods characterized by
      a pre-oral 'great appendage'. Evidence from functional morphology and taphonomy
      suggests that Isoxys was able to migrate through the water column and was
      possibly exploiting hyperbenthic niches for food. Although certainly not unique,
      the case of Isoxys supports the idea that off-bottom animal interactions such as
      predation, associated with complex feeding strategies and behaviours (e.g.
      vertical migration and hunting) were established by the Early Cambrian. It also
      suggests that a prototype of a pelagic food chain had already started to build-up
      at least in the lower levels of the water column.

PMID- 19403537
TI  - Great tits growing old: selective disappearance and the partitioning of
      senescence to stages within the breeding cycle.
AB  - Deterioration of reproductive traits with age is observed in an increasing number
      of species. Although such deterioration is often attributed to reproductive
      senescence, a within-individual decline in reproductive success with age, few
      studies on wild animals have focused on direct fitness measures while accounting
      for selective disappearance and terminal effects, and to our knowledge none have
      determined how senescence effects arise from underlying reproductive traits. We
      show for female great tits that such an approach helps understanding of the
      onset, impact and architecture of senescence. Cross-sectional analysis of 49
      years of breeding data shows annual recruit production to decline from 3.5 years
      of age, this decline affecting 9 per cent of females each year. Longitudinal
      analyses, however, show that selective disappearance of poor-quality breeders
      partly masks senescence, which in fact starts at 2.8 years and affects 21 per
      cent of females each year. There is no evidence for abrupt terminal effects.
      Analyses of underlying traits show no deterioration in clutch size, but
      significant declines in brood size and fledgling number. Furthermore, these
      traits contribute -9, 12 and 39 per cent to the senescent decline in recruit
      production, respectively. Besides providing detailed knowledge of the patterns
      and architecture of senescence in a natural population, these results illustrate
      the importance of modelling individual variation, and facilitate study of the
      underlying mechanisms of senescence.

PMID- 19403538
TI  - Group differences in the heritability of items and test scores.
AB  - It is important to understand potential sources of group differences in the
      heritability of intelligence test scores. On the basis of a basic item response
      model we argue that heritabilities which are based on dichotomous item scores
      normally do not generalize from one sample to the next. If groups differ in mean
      ability, the functioning of items at different ability levels may result in group
      differences in the heritability of items, even when these items function
      equivalently across groups and the heritability of the underlying ability is
      equal across groups. We illustrate this graphically, by computer simulation, and
      by focusing on several problems associated with a recent study by Rushton et al.
      who argued that the heritability estimates of items of Raven's Progressive
      Matrices test in North-American twin samples generalized to other population
      groups, and hence that the population group differences on this test of general
      mental ability (or intelligence) had a substantial genetic component. Our results
      show that item heritabilities are strongly dependent on the group on which the
      heritabilities were based. Rushton et al.'s results were artefactual and do not
      speak to the nature of population group differences in intelligence test
      performance.

PMID- 19403539
TI  - Bayesian phylogenetic analysis of Semitic languages identifies an Early Bronze
      Age origin of Semitic in the Near East.
AB  - The evolution of languages provides a unique opportunity to study human
      population history. The origin of Semitic and the nature of dispersals by Semitic
      speaking populations are of great importance to our understanding of the ancient
      history of the Middle East and Horn of Africa. Semitic populations are associated
      with the oldest written languages and urban civilizations in the region, which
      gave rise to some of the world's first major religious and literary traditions.
      In this study, we employ Bayesian computational phylogenetic techniques recently
      developed in evolutionary biology to analyse Semitic lexical data by modelling
      language evolution and explicitly testing alternative hypotheses of Semitic
      history. We implement a relaxed linguistic clock to date language divergences and
      use epigraphic evidence for the sampling dates of extinct Semitic languages to
      calibrate the rate of language evolution. Our statistical tests of alternative
      Semitic histories support an initial divergence of Akkadian from ancestral
      Semitic over competing hypotheses (e.g. an African origin of Semitic). We
      estimate an Early Bronze Age origin for Semitic approximately 5750 years ago in
      the Levant, and further propose that contemporary Ethiosemitic languages of
      Africa reflect a single introduction of early Ethiosemitic from southern Arabia
      approximately 2800 years ago.

PMID- 19403540
TI  - Tonically immobilized selfish prey can survive by sacrificing others.
AB  - Death-feigning, also called tonic immobility, is found in a number of animal
      species across vertebrate and invertebrate taxa. To date, five hypotheses have
      been proposed for the adaptive significance of tonic immobility. These are that
      tonic immobility is effective for prey because (i) avoiding dead prey is safer
      for predators, (ii) immobility plays a role in physical defence, (iii) immobility
      plays a role in concealment and/or background matching, (iv) predators lose
      interest in unmoving prey, and (v) the characteristic immobilization posture
      signals a bad taste to predators. The fourth and fifth hypotheses have been
      considered suitable explanations for tonic immobility of the red flour beetle
      against its predator, the jumping spider. In the present study, we used chemical
      analyses of secretions by the red flour beetles under attack by the jumping
      spider to reject the fifth hypothesis for this system. More importantly, we
      tested a selfish-prey hypothesis for the adaptive significance of death-feigning
      as an anti-predator strategy, in which individuals adopting tonic immobility
      survive by sacrificing neighbours. Findings showed that survival rates of
      feigners were higher when in the presence of non-feigners or prey of a different
      species, compared to when alone, thus confirming our selfish-prey hypothesis. In
      summary, our results suggest that immobility following a spider attack is
      selfish; death-feigning prey increase their probability of survival at the
      expense of more mobile neighbours.

PMID- 19403541
TI  - Growing with siblings: a common ground for cooperation or for fiercer competition
      among plants?
AB  - Recent work has shown that certain plants can identify their kin in competitive
      settings through root recognition, and react by decreasing root growth when
      competing with relatives. Although this may be a necessary step in kin selection,
      no clear associated improvement in individual or group fitness has been reported
      to qualify as such. We designed an experiment to address whether genetic
      relatedness between neighbouring plants affects individual or group fitness in
      artificial populations. Seeds of Lupinus angustifolius were sown in groups of
      siblings, groups of different genotypes from the same population and groups of
      genotypes from different populations. Both plants surrounded by siblings and by
      genotypes from the same population had lower individual fitness and produced
      fewer flowers and less vegetative biomass as a group. We conclude that genetic
      relatedness entails decreased individual and group fitness in L. angustifolius.
      This, together with earlier work, precludes the generalization that kin
      recognition may act as a widespread, major microevolutionary mechanism in plants.

PMID- 19403542
TI  - Puppy in a cyst: "I'm trapped! Help please!".

PMID- 19403543
TI  - Dedifferentiated epithelial-myoepithelial carcinoma of the parotid gland with
      aberrant expression of prostate specific antigen: a case report.
AB  - This report describes a rare case of dedifferentiated epithelial-myoepithelial
      carcinoma (EMCa) of the parotid gland. The tumor had 2 distinct components; a
      well-differentiated EMCa comprising of ductal and myoepithelial cells with low
      nuclear grade and low proliferation index. The second component showed a
      completely different morphology comprising of sheets and clusters of poorly
      differentiated cells with high nuclear grade and proliferative activity. The
      dedifferentiation was associated with an accelerated clinical course.
      Dedifferentiated EMCa is extremely rare with only 8 cases reported in the English
      literature. An unusual feature, hitherto not described in this tumor is the
      aberrant expression of prostate-specific antigen in the dedifferentiated
      component. In male patients, this may cause diagnostic confusion with metastatic
      prostate carcinoma.

PMID- 19403544
TI  - A case of juxtaglomerular cell tumor with novel histologic features.
AB  - Juxtaglomerular cell tumors constitute a very small group among the renal
      neoplasms. Most secrete renin, causing hypertension and hypokalemia due to
      secondary hyperaldosteronism. They have characteristic pathological features. For
      the accurate evaluation, diagnosis has to be confirmed by immunohistochemical
      staining for renin or electron microscopic demonstration of renin protogranules.
      This report presents a case of renal juxtaglomerular cell tumor in a 63-year-old
      man with previously unreported histological findings in addition to classic
      morphology.

PMID- 19403545
TI  - Absence of peritumoral fibrosis or inflammatory infiltrate may be related to
      clinical progression of papillary thyroid microcarcinoma.
AB  - Rio Grande do Norte (RN) shows the highest relative incidence of papillary
      carcinomas in Brazil. To analyze histological features that might be associated
      with this incidence, the authors compared thyroid glands from 463 autopsies
      performed in RN with 427 surgical and autopsy glands previously studied in Sao
      Paulo (SP). The authors found 41 papillary thyroid microcarcinomas (PTMs) in 35
      glands (8.1%), an incidence similar to the one reported in SP (7.8%). However,
      PTMs were predominantly nonencapsulated nonsclerosing at microscopy (44.0%), in
      contrast with SP where these types of lesion represented only 4 out of 32 PTMs
      (12.5%; P = .0046). The authors suggest that these nonencapsulated lesions with
      no sign of inflammation may represent an early stage that may evolve to clinical
      cancers, contributing to the high incidence of clinically differentiated thyroid
      carcinomas observed in RN.

PMID- 19403547
TI  - Distinctive morphology of renal cell carcinomas in tuberous sclerosis.
AB  - Tuberous sclerosis complex results from mutations in 1 of 2 interacting gene
      products, hamartin or tuberin. The syndrome is characterized by hamartomas and
      neoplastic lesions, including angiomyolipomas of the kidney and other organs.
      Renal cell carcinoma (RCC) in tuberous sclerosis remains relatively poorly
      characterized because historical studies were confounded by the inclusion of
      epithelioid angiomyolipomas. The authors present a patient with tuberous
      sclerosis and bilateral renal lesions, including multiple minute angiomyolipomas,
      cortical cysts, and 4 separate RCCs of unclassified type. The carcinomas shared
      distinctive morphological features, including sheet-like, glandular, trabecular,
      or cystic architecture and abundant granular eosinophilic cytoplasm. By
      definition, the carcinomas were keratin positive and negative for HMB-45 and
      Melan-A. Detailed immunohistochemical analysis revealed heterogeneity among the
      cortical cysts and carcinomas. The histopathological features of these carcinomas
      illustrate characteristics of renal carcinoma that are probably related to
      genetic alterations of tuberous sclerosis.

PMID- 19403546
TI  - Angiogenesis in the progression of breast ductal proliferations.
AB  - Angiogenesis, the formation of blood vessels, is necessary for a tumor to grow,
      but when angiogenesis first appears in the progression of breast ductal
      carcinomas is unknown. To determine when this occurs, the authors examined
      microvessel density (MVD) by CD31 and CD105 immunostaining in normal ducts, 32
      cases of usual hyperplasia, 19 cases of atypical hyperplasia, and 29 cases of
      ductal carcinoma in situ (DCIS). Simple hyperplasia had a 22-fold greater MVD
      than normal ducts (P < .0001). An increase during the progression of ductal
      changes was highly significant (P < .0001). To determine a possible mechanism,
      immunohistochemistry for vascular endothelial growth factor (VEGF) was evaluated.
      VEGF staining intensity of ductal epithelium increased during the progression
      from normal to hyperplastic to DCIS. This study shows that the first significant
      increase in angiogenesis occurs very early in the evolution of ductal
      proliferations as ductal cells become hyperplastic.

PMID- 19403548
TI  - Acute malnutrition in Bangladeshi children: levels and determinants.
AB  - The main purpose of the study was to identify the levels and determinants of
      acute malnutrition or wasting in Bangladeshi children. A 2-stage stratified
      random sampling design was used to collect the Bangladesh Demographic and Health
      Survey data during November 1999 to March 2000, in which 5333 living children
      aged 0 to 59 months and their mothers were weighed and measured to obtain their
      anthropometric data. The prevalence of wasting was assessed by the z scores
      approach, using the anthropometric criterion of weight-for-height and following
      the WHO guidelines and cutoff points. RESULTS: reveal that the prevalence of
      severe and moderate wasting were more common among children, and the overall
      prevalence of acute malnutrition was about 10%, indicating that it is one of the
      major public health problems in the country. Multivariate analysis showed that
      mother's BMI and media exposure, child's age and birth size, and respiratory
      sickness in childhood were significantly associated with both severe and moderate
      wasting.

PMID- 19403549
TI  - Does assessing error in perceiving postural limits by testing functional reach
      predict likelihood of falls in hospitalized stroke patients?
AB  - OBJECTIVE: To investigate the relationship between errors in perceiving postural
      limits and falls in hospitalized hemiplegic patients and to determine whether
      this relationship is useful for identifying patients at high risk of falls.
      DESIGN: Observational study. SUBJECTS: Seventy-six hemiplegic patients who were
      admitted to a rehabilitation hospital. METHODS: Error in perceiving postural
      limits was defined as the difference between the estimated maximum reach and
      actual reach distances, and its relationship to falls during hospitalization was
      investigated. Other measurements included Functional Ambulation Category,
      Brunnstrom's recovery stage, sensory disturbance, fear of falling and the
      Japanese version of the Montgomery-Asberg Depression Rating Scale (MADRS-J).
      RESULTS: For the multiple fall group, the error in estimated distance (EED) was
      significantly greater than that for the zero/single fall group (P < 0.01).
      Stepwise logistic regression analysis showed that EED (odds ratio 1.2, 95%
      confidence interval (CI) 1.1-1.4, P < 0.01) and MADRS-J scores (odds ratio 1.1,
      95% CI 1.0-1.3, P < 0.05) were correlated with multiple falls. According to the
      receiver operating characteristic curve for EED, the cut-off value for
      discriminating multiple fallers was 6.3 cm (sensitivity 81.0%, specificity 78.2%,
      area under the curve 0.8). CONCLUSIONS: The results suggest that assessing error
      in perceiving postural limits by measuring the maximum reach of the non-affected
      side of hemiplegic patients is one way to identify those who are at high risk for
      falling.

PMID- 19403550
TI  - Effects of plantar hardness discrimination training on standing postural balance
      in the elderly: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effects of sensory perception exercises for
      discrimination of surface hardness by the soles of the feet on standing postural
      balance in the elderly. DESIGN: A randomized two-group parallel controlled trial.
      SUBJECTS: Twenty-four healthy people aged from 61 to 71 years were enrolled and
      randomly assigned to a perception exercise group (n = 12) or a control group (n =
      12). INTERVENTION: The perception exercise group were given a task designed to
      train ability to discriminate different degrees of hardness of foam rubber. The
      training period was 10 days. Control group subjects were instructed to maintain a
      standing posture on foam rubber for 10 seconds for a total of 10 days.
      MEASUREMENTS: Before and after training we measured centre-of-gravity sway with
      the subject standing, obtaining sway path length and area of ellipse. The
      Functional Reach Test was used to measure the forward displacement distance of
      the centre of gravity. RESULTS: Our data revealed a significant reduction in
      centre-of-gravity sway post training in the perception exercise group as well as
      a significant increase in forward displacement of the centre of gravity. These
      parameters were unchanged in the control group. As to change values (difference
      between pre- and post-training values), the perception exercise group had
      significantly better values than the control group, indicating the efficacy of
      sensory perception exercises. CONCLUSIONS: We demonstrated that standing postural
      balance was improved by sensory perception exercises involving the soles of the
      feet. Used in addition to balance training, such training for hardness
      discrimination could be effective in the clinical setting to improve balance in
      the elderly.

PMID- 19403551
TI  - Self- and manual mobilization improves spine mobility in men with ankylosing
      spondylitis--a randomized study.
AB  - AIMS: To evaluate effects of physiotherapeutic intervention in terms of self- and
      manual mobilization on chest expansion, vital capacity, posture, spine mobility
      and experienced consequences of the disease in patients with ankylosing
      spondylitis. DESIGN: A prospective, randomized controlled study. METHODS: Thirty
      two men, aged between 23 and 60 years, with ankylosing spondylitis were
      randomized to active or no treatment for eight weeks. Physiotherapeutic
      intervention included individualized self- and manual mobilization for 1 hour
      twice a week and individually adjusted home exercises. Two blinded investigators
      made the assessments of chest expansion, posture and spinal mobility before and
      after the treatment period. The patient filled in three and the physiotherapist
      one of the four Bath Ankylosing Spondylitis scales (BAS scales). RESULTS: In the
      treatment group chest expansion increased at the level of processus xiphoideus
      (P<0.01), with no difference in vital capacity compared with the control group.
      The posture improved in the cervical (C7-wall distance) (P<0.001) and in the
      thoracic spine (P<0.05). Thoracic and lumbar spine flexion improved (P<0.01) as
      did sagittal range of motion P<0.001 and P<0.01, respectively. The Bath
      Ankylosing Spondylitis Metrology Index total scoring improved (P<0.001) in the
      treatment group compared with the control group. The other three BAS scales
      showed no differences between groups. At four months follow-up of the treatment
      group, cervical spine posture, lumbar flexion and range of motion as well as BAS
      Metrology Index were still improved. CONCLUSION: This study shows that eight
      weeks of self- and manual mobilization treatment improved chest expansion,
      posture and spine mobility in patients with ankylosing spondylitis.

PMID- 19403552
TI  - A preliminary investigation of a novel design of visual cue glasses that aid gait
      in Parkinson's disease.
AB  - OBJECTIVE: Parkinson's disease is a relatively common progressive
      neurodegenerative disorder, one of whose main features is difficulty with
      walking. This can be partially corrected by providing cues for the placement of
      each step. We piloted the potential benefit of simple custom-designed 'walking
      glasses' worn by the patient that provide visual and auditory cues to aid in step
      placement. DESIGN: We used a repeated measures design to compare gait performance
      when unaided and when using the walking glasses with different patterns of visual
      and auditory stimulation by timing patients' walking over a 'real-life'
      predefined 30-m course. SETTING: Hospital outpatient clinic. SUBJECTS: Fifteen
      patients with idiopathic Parkinson's disease who had significant gait problems
      and no other condition affecting gait performance. MAIN MEASURES: Timed walk.
      RESULTS: Using the glasses, 8 of 15 patients achieved a significant and
      meaningful average improvement in walking time of at least 10% (mean (95%
      confidence interval) improvement in these patients was 21.5% (3.9%)), while a
      further 2 had subjective and modest objective benefit. Different patterns of
      visual and auditory cues suited different patients. Visual cueing alone with a
      fixed horizontal cue line present all the time statistically resulted in the
      greatest improvement in walking time. CONCLUSIONS: This pilot study shows
      promising improvement in the gait of a significant proportion of Parkinson's
      disease patients through the use of a simple, inexpensive and robust design of
      walking glasses, suggesting practical applicability in a therapy setting to large
      numbers of such patients.

PMID- 19403553
TI  - Randomized controlled trial for clinical effects of varying types of insoles
      combined with specialized shoes in patients with rheumatoid arthritis of the
      foot.
AB  - OBJECTIVE: To determine the effects of specialized shoes with insoles in patients
      with rheumatoid arthritis and the differences in terms of type of insole and
      anatomical location of foot pathology. DESIGN: Single-blinded randomized
      controlled trial. SETTING: Outpatients of physical medicine and rehabilitation
      clinic at university hospital. SUBJECTS: Forty-two patients with rheumatoid foot
      lesions were randomly assigned to two different orthotic intervention groups. The
      anatomical locations of the foot lesions were recorded (hindfoot or forefoot).
      INTERVENTION: Participants were provided with an extra deep forefoot-rockered
      shoe and either a custom-made semi-rigid insole or a ready-made simple soft
      insole. They wore the provided footwear for at least 3 hours a day over six
      months. MAIN OUTCOME MEASURES: Primary outcome measures were foot pain visual
      analogue scale (VAS) scores and Foot Function Index (FFI). Secondary outcome
      measures were erythrocyte sedimentation rate and C-reactive protein levels in
      blood, amounts of medications and active joint counts. These were checked at
      baseline and post intervention. RESULTS: Eight patients dropped out at follow-up
      after six months of treatment. At six-month follow-ups, VAS scores and total Foot
      Function Index scores had decreased significantly in both groups versus baseline
      but intergroup comparison showed no significant differences in view of type of
      insoles and anatomical locations of foot pathology. CONCLUSIONS: We were unable
      to identify differences between the types of insoles in terms of their clinical
      effects or between anatomical locations of foot lesions in the two groups, but
      both groups improved. Therapeutic shoes plus soft insoles might be effective
      enough in terms of foot pain and foot function for specific patients with
      rheumatoid foot problems regardless of the location of foot pathology.

PMID- 19403555
TI  - Clinical examination tools for lateropulsion or pusher syndrome following stroke:
      a systematic review of the literature.
AB  - OBJECTIVE: To examine the clinimetric properties and clinical applicability of
      published tools for 'quantifying' the degree of lateropulsion or pusher syndrome
      following stroke. DATA SOURCES: Search through electronic databases (MEDLINE,
      EMBASE, CINAHL, Science Citation Index) with the terms lateropulsion, pushing,
      pusher syndrome, validity, reliability, internal consistency, responsiveness,
      sensitivity, specificity, posture and stroke. Databases were searched from their
      inception to October 2008. REVIEW METHODS: Abstracts were selected by one author.
      A panel of experts then determined which should be included in this review. Five
      abstracts were reviewed and the panel agreed to omit one abstract because those
      authors did not write a full manuscript. The panel critiqued manuscripts
      according to predetermined criteria about clinical and clinimetric properties.
      RESULTS: Four manuscripts referencing three tools for examining lateropulsion
      were found. Validity and reliability data support the clinical use of the Scale
      for Contraversive Pushing, the Modified Scale for Contraversive Pushing and the
      Burke Lateropulsion Scale. The Scale for Contraversive Pushing has the most
      extensive testing of clinimetric properties. The other tools show promising
      preliminary evidence of clinical and research utility. More testing is needed
      with larger, more diverse samples. REVIEWERS' CONCLUSIONS: The Scale for
      Contraversive Pushing, the Modified Scale for Contraversive Pushing and the Burke
      Lateropulsion Scale are reliable and valid measures with good clinical
      applicability. Larger, more varied samples should be used to better delineate
      responsiveness and other clinimetric properties of these examination tools.

PMID- 19403554
TI  - Person--environment fit predicts falls in older adults better than the
      consideration of environmental hazards only.
AB  - OBJECTIVE: To test the hypotheses that the empirical consideration of objective
      person-environment fit in the home environment is a stronger predictor of indoor
      falls among older adults than the assessment of environmental barriers only, and
      that perceived aspects of home play a role as predictors for falls. DESIGN:
      Survey study with data collection at home visits, followed up by self-reports
      about falls at home visits one year later. SETTING: Urban districts in Sweden,
      Germany, Latvia. PARTICIPANTS: Eight hundred and thirty-four single-living, older
      adults (75-89 years), in ordinary housing. MEASUREMENTS: An assessment of
      objective person-environment fit in the home environment (housing enabler), a
      self-rating of the perceived home environment (usability in my home) and
      retrospective self-reports on indoor falls. RESULTS: The participants reporting
      falls tended to be frailer than the non-fallers. The number of environmental
      barriers in the home was similar for the fallers and non-fallers; the magnitude
      of person-environment fit problems was higher among the fallers. The person
      environment fit problem variable was a stronger fall predictor (odds ratio (OR) =
      1.025; P=0.037) than number of environmental barriers (n.s.), even after
      controlling for confounders. Fallers also experienced lower usability of their
      home. CONCLUSION: The results suggest that much of the inconclusiveness of the
      data in the relationship between environmental hazards and falls in the previous
      falls literature could be due to the neglect of person-environment fit
      assessment. The effectiveness of environmental interventions based on the notion
      of person-environment fit compared with traditional home hazard checklists
      remains to be tested.

PMID- 19403556
TI  - Changing self-efficacy in individuals following a first time stroke: preliminary
      study of a novel self-management intervention.
AB  - OBJECTIVE: To examine the effects of a self-management workbook intervention
      designed for use with individuals disabled after first time stroke. DESIGN:
      Multiple-participant two-phase (baseline followed by treatment) single subject
      design. The intervention was introduced at a randomly generated time-point.
      SETTING: Community. SUBJECTS: Seven men and three women, with a mean age of 61.5
      years (SD 8.15), on average 24.2 weeks (SD 18.29) following first stroke, all
      with residual restriction of activity and participation. INTERVENTION: An
      individualized self-management workbook based on self-efficacy principles,
      incorporating sections to increase mastery, vicarious experience and feedback.
      MAIN MEASURES: Stroke Self-Efficacy Questionnaire, General Self-Efficacy Scale,
      Recovery Locus of Control Scale, Rivermead Mobility Index, Rivermead Activities
      of Daily Living Scale, Subjective Index of Physical and Social Outcome and the
      Hospital Anxiety and Depression Scale. Individual data were analysed with
      weighted mean trend test and two standard deviation band test. Group data were
      analysed with a randomization test. RESULTS: Visual inspection of the data over
      the 14-week period showed steady improvement for all of the 10 participants on
      the majority of variables. A randomization test indicated a statistically
      significant change in Stroke Self-Efficacy Questionnaire scores and Recovery
      Locus of Control Scale scores which followed introduction of the intervention.
      Measures of activity, participation and mood scores did not show a statistically
      significant change. CONCLUSION: There is preliminary evidence that the use of an
      individualized stroke self-management intervention is acceptable and can lead to
      a change in self-efficacy in this small sample.

PMID- 19403557
TI  - Deletions and missense mutations of EPM2A exacerbate unfolded protein response
      and apoptosis of neuronal cells induced by endoplasm reticulum stress.
AB  - The majority of the Lafora's disease (LD) is caused by defect in the EPM2A gene,
      including missense and nonsense mutations and deletions. These defects mainly
      occur in the carbohydrate-binding domain, and how these mutations cause neuronal
      defects is under active investigation. Here, we report that the mutant proteins
      encoded by all missense mutations and most deletions tested are unstable,
      insoluble and ubiquitinated, and are accumulated in aggresome-like structures.
      The effect of apparent 'gain-of-function' mutations can be corrected by co
      transfection of wild-type EPM2A cDNA, which is consistent with the recessive
      nature of these mutations in LD patients. In a neuronal cell line, these mutant
      aggregates exacerbate endoplasm reticulum (ER) stress and make the cells
      susceptible to the apoptosis induced by ER stressor, thapsigargin. The chemical
      chaperon, 4-phenylbutyrate, increased the mutant solubility, reduced the ER
      stress and dulled the sensitivity of mutant neuronal cells to apoptosis induced
      by thapsigargin and the mutant laforin proteins. The increased sensitivity to ER
      stress-induced apoptosis may contribute to LD pathogenesis.

PMID- 19403558
TI  - The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional
      modifications of E-cadherin.
AB  - It has long been recognized that E-cadherin dysfunction is a major cause of
      epithelial cell invasion. However, very little is known about the post
      transcriptional modifications of E-cadherin and its role in E-cadherin mediated
      tumor progression. N-acetylglucosaminyltransferase III (GnT-III) catalyzes the
      formation of a bisecting GlcNAc structure in N-glycans, and has been pointed as a
      metastasis suppressor. N-acetylglucosaminyltransferase V (GnT-V) catalyzes the
      addition of beta1,6 GlcNAc branching of N-glycans, and has been associated to
      increase metastasis. The regulatory mechanism between E-cadherin expression and
      the remodeling of its oligosaccharides structures by GnT-III and GnT-V were
      explored in this study. We have demonstrated that wild-type E-cadherin regulates
      MGAT3 gene transcription resulting in increased GnT-III expression. We also
      showed that GnT-III and GnT-V competitively modified E-cadherin N-glycans. The
      GnT-III knockdown cells revealed a membrane de-localization of E-cadherin leading
      to its cytoplasmic accumulation. Further, the GnT-III knockdown cells also caused
      modifications of E-cadherin N-glycans catalyzed by GnT-III and GnT-V. Altogether
      our results have clarified the existence of a bidirectional crosstalk between E
      cadherin and GnT-III/GnT-V that was, for the first time, reproduced in an in vivo
      model. This study opens new insights into the post-transcriptional modifications
      of E-cadherin in its biological function, in a tumor context.

PMID- 19403559
TI  - Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no
      association with severe malaria phenotypes.
AB  - The prevalence of CD36 deficiency in East Asian and African populations suggests
      that the causal variants are under selection by severe malaria. Previous analysis
      of data from the International HapMap Project indicated that a CD36 haplotype
      bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive
      selection in the Yoruba of Nigeria. To investigate the global distribution of
      this putative selection event, we genotyped T1264G in 3420 individuals from 66
      populations. We confirmed the high frequency of 1264G in the Yoruba (26%).
      However, the 1264G allele is less common in other African populations and absent
      from all non-African populations without recent African admixture. Using long
      range linkage disequilibrium, we studied two West African groups in depth.
      Evidence for recent positive selection at the locus was demonstrable in the
      Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an
      association with severe malaria phenotypes, employing a case-control study of
      1350 subjects and a family study of 1288 parent-offspring trios. No marker was
      significantly associated with severe malaria. We focused on T1264G, genotyping
      10,922 samples from four African populations. The nonsense allele was not
      associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence
      interval 0.89-1.12; P = 0.98). These results suggest a range of possible
      explanations including the existence of alternative selection pressures on CD36,
      co-evolution between host and parasite or confounding caused by allelic
      heterogeneity of CD36 deficiency.

PMID- 19403560
TI  - The role of senescence and prosurvival signaling in controlling the oncogenic
      activity of FGFR2 mutants associated with cancer and birth defects.
AB  - Mutations in fibroblast growth factor receptors (FGFRs) cause human birth defect
      syndromes and are associated with a variety of cancers. Although forced
      expression of mutant activated FGFRs has been shown to oncogenically transform
      some immortal cell types, their activity in primary cells remains unclear. Here,
      we show that birth defect and cancer-associated FGFR2 mutants promote DNA-damage
      signaling and p53-dependent senescence in primary mouse and human cells.
      Senescence promoted by FGFR mutants was associated with downregulation of c-Myc
      and forced expression of c-Myc facilitated senescence escape. Whereas c-Myc
      expression facilitated senescence bypass, mutant FGFR2 signaling suppressed c-Myc
      dependent apoptosis and led to oncogenic transformation. Cells transformed by
      coexpression of a constitutively activated FGFR2 mutant plus c-Myc appeared to be
      become highly addicted to FGFR-dependent prosurvival activities, as small
      molecule inhibition of FGFR signaling resulted in robust p53-dependent apoptosis.
      Our data suggest that senescence-promoting activities of mutant FGFRs may
      normally limit their oncogenic potential and may be relevant to their ability to
      disrupt morphogenesis and cause birth defects. Our results also raise the
      possibility that cancers originating through a combination of constitutive FGFR
      activation and deregulated Myc expression may be particularly sensitive to small
      molecule inhibitors of FGF receptors.

PMID- 19403561
TI  - HoxB5 induces endothelial sprouting in vitro and modifies intussusceptive
      angiogenesis in vivo involving angiopoietin-2.
AB  - AIMS: Homeobox (Hox) proteins are transcriptional regulators in embryonic
      patterning, cell differentiation, proliferation, and migration in vertebrates and
      invertebrates. A growing body of evidence suggests that Hox proteins are involved
      in endothelial cell regulation. We have shown earlier that HoxB5 upregulates
      vascular endothelial growth factor receptor-2 and thereby contributes to enhanced
      endothelial precursor cell differentiation. Here we aim to elucidate the role of
      HoxB5 in angiogenesis. METHODS AND RESULTS: Endothelial cell sprouting was
      investigated in the human umbilical vein endothelial cell spheroid assay. We
      investigated in vivo angiogenesis in the chick (Gallus gallus) chorioallantoic
      membrane assay. Expression profiling of proangiogenic factors was done by
      quantitative PCR. The angiopoietin-2 (Ang2) promoter and deletion fragments
      thereof were cloned into the pGL3 reporter system for analysis of transcriptional
      activity. We observed that HoxB5 enhances endothelial cell sprouting and
      modulates the expression of adhesion molecules in vitro. Accordingly, we observed
      a modification of vascular growth by HoxB5 in vivo. The HoxB5 effect is
      reminiscent of the effects of angiopoietins. We demonstrate that Ang2 is
      upregulated upon HoxB5 overexpression and that the HoxB5 effect is abolished by
      the angiopoietin antagonist soluble Tie-2. CONCLUSION: HoxB5 has an activating
      effect on Ang2 that is essential for endothelial cell sprouting and coordinated
      vascular growth.

PMID- 19403562
TI  - Genetic polymorphisms of GnRH and gonadotrophic hormone receptors affect the
      phenotype of polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex genetic disorder.
      Multiple functional polymorphisms have been identified in genes that regulate the
      hypothalamic-pituitary-gonadal (HPG) axis that regulates ovarian function. The
      present study aims to examine the influence of genetic variants of the HPG-axis
      on the severity of clinical features of PCOS and disease susceptibility. METHODS:
      We included 518 Caucasian PCOS women and 2996 unselected controls from the
      general population (the Rotterdam study). Genotype distributions were compared
      between patients and controls. Subsequently, associations with clinical features
      of PCOS were studied. Single nucleotide polymorphisms were selected in GnRH
      (Trp16Ser [rs6185]), the FSH-receptor (FSHR, Ala307Thr [rs6165] and Asn680Ser
      [rs6166]) and the LH-receptor (18insLQ, Asn291Ser [rs12470652] and Ser312Asn
      [rs2293275]). RESULTS: FSHR Ser(680) was associated with higher levels of
      gonadotrophic hormones (FSH: P < 0.01, LH: P = 0.01), and testosterone (P = 0.05)
      and a higher frequency of hyperandrogenism (P = 0.04). No differences in risk for
      PCOS in association with the FSH-receptor variants were observed. CONCLUSION:
      Genetic variants of the HPG-axis were associated with a modest but significant
      effect on the phenotype of PCOS. FSHR variants were strongly associated with the
      severity of clinical features of PCOS, such as levels of gonadotrophic hormones
      and the presence of hyperandrogenism, but not disease risk.

PMID- 19403563
TI  - ESHRE PGD Consortium data collection IX: cycles from January to December 2006
      with pregnancy follow-up to October 2007.
AB  - The ninth report of the European Society of Human Reproduction and Embryology
      Preimplantation Genetic Diagnosis Consortium is presented documenting cycles
      collected for the calendar year 2006 and follow-up of the pregnancies and babies
      born until October 2007, which resulted from these cycles. Since the beginning of
      the data collections there has been a steady increase in the number of cycles,
      pregnancies and babies reported annually. For data collection IX, 57 centres have
      participated, reporting on 5858 cycles to oocyte retrieval (OR), along with
      details of the follow-up on 1437 pregnancies and 1206 babies born. Eight hundred
      and twelve ORs were reported for chromosomal abnormalities, 133 ORs for sexing
      for X-linked diseases, 931 ORs for monogenic diseases, 3900 ORs for
      preimplantation genetic screening and 82 ORs for social sexing. Data IX are
      compared with the cumulative data for data collections I-VIII.

PMID- 19403564
TI  - Influence of sex on the meiotic segregation of a t(13;17) Robertsonian
      translocation: a case study in the pig.
AB  - BACKGROUND: Comparison of male versus female meiotic segregation patterns for
      Robertsonian translocation (RT) carriers with similar genetic background has
      rarely been reported in mammalian species. METHODS: The aim of this study was to
      compare the segregation patterns determined for related males and females
      carrying a 13;17 RT in an animal model (Sus scrofa domestica L.), using dual
      colour fluorescence in situ hybridization on decondensed sperm nuclei and
      metaphases II of in vitro-matured oocytes. RESULTS: In males, no association
      between the trivalent and the XY body was observed in any of the 90 pachytene
      nuclei studied, and the rate of unbalanced spermatozoa ranged between 2.96% and
      3.83%. Female meiotic segregation analyses were carried out on 83 metaphase II
      oocytes. The rate of unbalanced gametes was higher in females than in males
      (28.91% versus 3.21%, P < 0.001). This difference was due to higher rates of
      diploid gametes (12.04% versus 0.05%) and unbalanced gametes produced by the
      adjacent segregation (16.86% versus 3.16%). CONCLUSIONS: This study is a new
      scientific contribution to the comparison of segregation patterns in related
      males and females carrying an identical chromosomal rearrangement. It allows a
      better understanding of the meiotic behaviour of RTs. It also clearly illustrates
      the relevance of swine as an animal model for such meiotic studies.

PMID- 19403566
TI  - Role of DNA methylation in the tissue-specific expression of the CYP17A1 gene for
      steroidogenesis in rodents.
AB  - The CYP17A1 gene is the qualitative regulator of steroidogenesis. Depending on
      the presence or absence of CYP17 activities mineralocorticoids, glucocorticoids
      or adrenal androgens are produced. The expression of the CYP17A1 gene is tissue
      as well as species-specific. In contrast to humans, adrenals of rodents do not
      express the CYP17A1 gene and have therefore no P450c17 enzyme for cortisol
      production, but produce corticosterone. DNA methylation is involved in the tissue
      specific silencing of the CYP17A1 gene in human placental JEG-3 cells. We
      investigated the role of DNA methylation for the tissue-specific expression of
      the CYP17A1 gene in rodents. Rats treated with the methyltransferase inhibitor 5
      aza-deoxycytidine excreted the cortisol metabolite tetrahydrocortisol in their
      urine suggesting that treatment induced CYP17 expression and 17alpha-hydroxylase
      activity through demethylation. Accordingly, bisulfite modification experiments
      identified a methylated CpG island in the CYP17 promoter in DNA extracted from
      rat adrenals but not from testes. Both methyltransferase and histone deacetylase
      inhibitors induced the expression of the CYP17A1 gene in mouse adrenocortical Y1
      cells which normally do not express CYP17, indicating that the expression of the
      mouse CYP17A1 gene is epigenetically controlled. The role of DNA methylation for
      CYP17 expression was further underlined by the finding that a reporter construct
      driven by the mouse -1041 bp CYP17 promoter was active in Y1 cells, thus
      excluding the lack of essential transcription factors for CYP17 expression in
      these adrenal cells.

PMID- 19403565
TI  - Lithium chloride treatment induces epithelial cell proliferation in xenografted
      human endometrium.
AB  - BACKGROUND: In mouse endometrium, glycogen synthase kinase-3beta (GSK3beta) is a
      key enzyme controlling nuclear localization of cyclin D1. We developed a
      functional model of xenografted human endometrium to test whether similar
      mechanisms are operative in the human by using Lithium chloride (LiCl), an
      inhibitor of GSK3beta. METHODS: Human endometrial samples were obtained from
      normal volunteers, then implanted under the kidney capsule of nude mice, and
      treated with estradiol-17beta (E2) or LiCl. Xenografts were assessed for protein
      expression of MKI-67, mini-chromosome maintenance protein-2, estrogen receptor
      (ER), progesterone receptor (PR) and cyclin D1. RESULTS: Both E2 and LiCl induced
      a robust proliferative response in the epithelium. Only lithium treatment
      produced clear nuclear localization of cyclin D1 consistent with the
      proliferative response observed. Regenerated endometrium had detectable ER and PR
      expression. CONCLUSION: Xenografted human endometrium provides a dynamic model of
      uterine biology. Administration of LiCl in the absence of E2 induced epithelial
      proliferation, supporting the hypothesis that human and murine endometrial
      proliferation may share key regulatory pathways. These data suggest a possible
      link between the increased menstrual disturbances in women with affective
      disorders taking lithium and the consequent potential for the development of
      endometrial proliferative disorder.

PMID- 19403569
TI  - A 4 year old boy with recurrent wheeze and chest infections.

PMID- 19403567
TI  - Changes of agouti-related protein in hypothalamus, placenta, and serum during
      pregnancy in the rat.
AB  - Agouti-related protein (AGRP) is a homolog of the agouti protein and acts as an
      antagonist of peptides derived from propiomelanocortin through melanocortin
      receptors. This peptide is produced mainly in the hypothalamus, particularly
      during negative energy balance and influences increased food intake. In the
      hypothalamus, this peptide is co-expressed in arcuate nuclei with neuropeptide Y,
      another important peptide that regulates energy metabolisms. In our study, we
      analyzed changes in the Agrp mRNA level in the hypothalamus as well as mRNA and
      protein levels in placenta during different stages of rat pregnancy. We also
      investigated the AGRP level in the blood serum. In this study, we found the AGRP
      level in serum increased, while its gene expression in the hypothalamus increased
      only up to the 13th day of pregnancy, and decreased on the 18th day. This study
      demonstrates that AGRP is expressed during late pregnancy in placenta. Moreover,
      we found that AGRP expression is higher on the 18th than on the 13th day of
      pregnancy. Our results indicate that AGRP may play an important role during
      pregnancy in the mother's and, possibly, also in the fetus's energy balance.

PMID- 19403568
TI  - Differential induction of LRP16 by liganded and unliganded estrogen receptor
      alpha in SKOV3 ovarian carcinoma cells.
AB  - Previously, we investigated the induction effect of LRP16 expression by estrogen
      (17beta-estradiol, E(2)) and established a feed-forward mechanism that activated
      estrogen receptor alpha (ERalpha) transactivation in estrogen-dependent
      epithelial cancer cells. LRP16 is required for ERalpha signaling transduction by
      functioning as an ERalpha coactivator. In this study, we demonstrated that LRP16
      expression was upregulated in E(2)-responsive BG-1 ovarian cancer cells, but was
      downregulated in estrogen-resistant SKOV3 ovarian cancer cells. Pure estrogen
      antagonist ICI 182 780 did not affect LRP16 expression in SKOV3 cell. The
      unliganded ERalpha upregulated LRP16 expression and enhanced LRP16 promoter
      activity in SKOV3 cells; however, this induction was blocked by estrogen
      stimulation. Results from chromatin immunoprecipitation experiment revealed a
      strong recruitment of the unliganded ERalpha at LRP16 promoter in the absence of
      estrogen; however, ERalpha was largely released from the DNA upon E(2)
      stimulation. Modulation in LRP16 expression level did not significantly change
      the proliferation rate of SKOV3 cells and the growth responsiveness of cells to
      E(2). Knockdown of LRP16 by RNA interference in SKOV3 cells markedly attenuated
      estrogen response element-dependent ERalpha reporter gene activity and E(2)
      induced c-Myc expression. Our study suggests a novel mechanism of estrogen
      resistance of ovarian cancer by which estrogen-repressed signaling pathway
      antagonizes estrogen-activated signaling transduction.

PMID- 19403570
TI  - A taxi driver with type 2 diabetes.

PMID- 19403573
TI  - Standardised mortality ratios. Neither constant nor a fallacy.

PMID- 19403574
TI  - Standardised mortality ratios. Institutional performance.

PMID- 19403575
TI  - Neurologist fails to quash GMC findings of research dishonesty.

PMID- 19403576
TI  - Swine flu could come back in more virulent form after summer, European experts
      say.

PMID- 19403577
TI  - Health department starts to stockpile masks for clinicians to combat swine flu.

PMID- 19403578
TI  - Cauda equina syndrome. Examination must be thorough.

PMID- 19403579
TI  - Cauda equina syndrome. Specialist rehabilitation.

PMID- 19403580
TI  - Cauda equina syndrome. Urinary retention.

PMID- 19403581
TI  - Nicotine replacement, effective?

PMID- 19403582
TI  - Tea and cancer. Why northern Iran?

PMID- 19403583
TI  - Tea and cancer. Role of temperature.

PMID- 19403584
TI  - Tea and cancer. And what of opium chewing?

PMID- 19403586
TI  - Surgery for breast cancer. Oncoplastic surgery is promising.

PMID- 19403587
TI  - The new BMJ online archive.

PMID- 19403588
TI  - Standardised mortality ratios. Monitoring mortality.

PMID- 19403589
TI  - Standardised mortality ratios. Methodological bias.

PMID- 19403591
TI  - The 2009 budget and the NHS.

PMID- 19403594
TI  - Protective effects of inhaled carbon monoxide in pig lungs during cardiopulmonary
      bypass are mediated via an induction of the heat shock response.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) may cause acute lung injury leading to
      increased morbidity and mortality after cardiac surgery. Preconditioning by
      inhaled carbon monoxide reduces pulmonary inflammation during CPB. We
      hypothesized that inhaled carbon monoxide mediates its anti-inflammatory and
      cytoprotective effects during CPB via induction of pulmonary heat shock proteins
      (Hsps). METHODS: Pigs were randomized either to a control group, to standard CPB,
      to carbon monoxide+CPB, or to quercetin (a flavonoid and unspecific inhibitor of
      the heat shock response)+control, to quercetin+CPB, and to quercetin+carbon
      monoxide+CPB. In the carbon monoxide groups, lungs were ventilated with 250 ppm
      carbon monoxide in addition to standard ventilation before CPB. At various time
      points, lung biopsies were obtained and pulmonary Hsp and cytokine concentrations
      determined. RESULTS: Haemodynamic parameters were largely unaffected by CPB,
      carbon monoxide inhalation, or administration of quercetin. Compared with
      standard CPB, carbon monoxide inhalation significantly increased the pulmonary
      expression of the Hsps 70 [27 (SD 3) vs 69 (10) ng ml(-1) at 120 min post-CPB,
      P<0.05] and 90 [0.3 (0.03) vs 0.52 (0.05) after 120 min CPB, P<0.05], induced the
      DNA binding of heat shock factor-1, reduced interleukin-6 protein expression [936
      (75) vs 320 (138) at 120 min post-CPB, P<0.001], and decreased CPB-associated
      lung injury (assessed by lung biopsy). These carbon monoxide-mediated effects
      were inhibited by quercetin. CONCLUSIONS: As quercetin, a Hsp inhibitor, reversed
      carbon monoxide-mediated pulmonary effects, we conclude that the anti
      inflammatory and protective effects of preconditioning by inhaled carbon monoxide
      during CPB in pigs are mediated by an activation of the heat shock response.

PMID- 19403595
TI  - Effects of four intraoperative ventilatory strategies on respiratory compliance
      and gas exchange during laparoscopic gastric banding in obese patients.
AB  - BACKGROUND: Respiratory function is impaired in obese patients undergoing
      laparoscopic surgery. This study was performed to determine whether repeated lung
      recruitment combined with PEEP improves respiratory compliance and arterial
      partial pressure of oxygen (Pa(O2)) in obese patients undergoing laparoscopic
      gastric banding. METHODS: Sixty patients with BMI >30 kg m(-2) were randomized,
      after induction of pneumoperitoneum, to receive either PEEP of 10 cm H2O (Group
      P), inspiratory pressure of 40 cm H2O for 15 s once (Group R), Group R
      recruitment followed by PEEP 10 cm H2O (Group RP), or Group RP recruitment but
      with the inspiratory manoeuvre repeated every 10 min (Group RRP). Static
      respiratory compliance and Pa(O2) were determined after intubation, 10 min after
      pneumoperitoneum (before lung recruitment), and every 10 min thereafter (after
      recruitment). Results are presented as mean (SD). RESULTS: Pneumoperitoneum
      decreased respiratory compliance from 48 (3) to 30 (1) ml cm H2O(-1) and
      decreased Pa(O2) from 12.4 (0.3) to 8.8 (0.3) kPa in all groups (P<0.01).
      Immediately after recruitment, compliance was 32 (1), 32 (2), 40 (2), and 40 (1)
      ml cm H2O(-1) and Pa(O2) was 9.1 (0.3), 9.1 (0.1), 11.9 (0.1), and 11.9 (0.1) kPa
      in Groups P, R, RP, and RRP, respectively (P<0.01). Ten and 20 min later, Pa(O2)
      in Group R decreased to 9.2 (0.1) kPa and compliance in Group PR decreased to 33
      (2) ml cm H2O(-1), respectively (P<0.01). CONCLUSIONS: Group RRP recruitment
      strategy was associated with the best intraoperative respiratory compliance and
      Pa(O2) in obese patients undergoing laparoscopic gastric banding.

PMID- 19403596
TI  - Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in
      rat carotid body glomus cells.
AB  - Carotid body (CB) glomus cells from rat express a TASK-like background K+ channel
      that is believed to play a critical role in the regulation of excitability and
      hypoxia-induced increase in respiration. Here we studied the kinetic behaviour of
      single channel openings from rat CB cells to determine the molecular identity of
      the 'TASK-like' K+ channels. In outside-out patches, the TASK-like background K+
      channel in CB cells was inhibited >90% by a reduction of pH(o) from 7.3 to 5.8.
      In cell-attached patches with 140 mM KCl and 1 mM Mg2+ in the bath and pipette
      solutions, two main open levels with conductance levels of approximately 14 pS
      and approximately 32 pS were recorded at a membrane potential of -60 mV. The K+
      channels showed kinetic properties similar to TASK-1 (approximately 14 pS), TASK
      3 (approximately 32 pS) and TASK-1/3 heteromer (approximately 32 pS). The
      presence of three TASK isoforms was tested by reducing [Mg2+](o) to approximately
      0 mM, which had no effect on the conductance of TASK-1, but increased those of
      TASK-1/3 and TASK-3 to 42 pS and 74 pS, respectively. In CB cells, the reduction
      of [Mg2+](o) to approximately 0 mM also caused the appearance of approximately 42
      pS (TASK-1/3-like) and approximately 74 pS (TASK-3-like) channels, in addition to
      the approximately 14 pS (TASK-1-like) channel. The 42 pS channel was the most
      abundant, contributing approximately 75% of the current produced by TASK-like
      channels. Ruthenium red (5 microM) had no effect on TASK-1 and TASK-1/3, but
      inhibited TASK-3 by 87%. In CB cells, ruthenium red caused approximately 12%
      inhibition of TASK-like activity. Methanandamide reduced the activity of all
      three TASKs by 80-90%, and that of TASK-like channels in CB cell also by
      approximately 80%. In CB cells, hypoxia caused inhibition of TASK-like channels,
      including TASK-1/3-like channels. These results show that TASK-1, TASK-1/3 and
      TASK-3 are all functionally expressed in isolated CB cells, and that the TASK-1/3
      heteromer provides the major part of the oxygen-sensitive TASK-like background K+
      conductance.

PMID- 19403597
TI  - Activation by Ca2+/calmodulin of an exogenous myosin light chain kinase in mouse
      arteries.
AB  - Activation of myosin light chain kinase (MLCK) and other kinases was studied in
      the arteries of transgenic mice that express an optical fluorescence resonance
      energy transfer (FRET) MLCK activity biosensor. Binding of Ca(2+)/calmodulin
      (Ca(2+)/CaM) induces an increase in MLCK activity and a change in FRET. After
      exposure to high external [K(+)], intracellular [Ca(2+)] (fura-2 ratio or fluo-4
      fluorescence) and MLCK activity both increased rapidly to an initial peak and
      then declined, rapidly at first and then very slowly. After an initial peak
      ('phasic') force was constant or increased slowly (termed 'tonic' force).
      Inhibition of rho-kinase (Y-27632) decreased tonic force more than phasic, but
      had little effect on [Ca(2+)] and MLCK activation. Inhibition of PKCalpha and
      PKCbeta with Go6976 had no effect. KN-93, an inhibitor of CaMK II, markedly
      reduced force, MLCK FRET and [Ca(2+)]. Applied during tonic force, forskolin
      caused a rapid decrease in MLCK FRET ratio and force, but no change in Ca(2+),
      suggesting a cAMP mediated decrease in affinity of MLCK for Ca(2+)/CaM. However,
      receptor (beta-adrenergic) activated increases in cAMP during KCl were
      ineffective in causing relaxation, changes in [Ca(2+)], or MLCK FRET. At the same
      tonic force, MLCK FRET ratio activated by alpha(1)-adrenoceptors was
      approximately 60% of that activated by KCl. In conclusion, MLCK activity of
      arterial smooth muscle during KCl-induced contraction is determined primarily by
      Ca(2+)/CaM. Rho-kinase is activated, by unknown mechanisms, and increases 'Ca(2+)
      sensitivity' significantly. Forskolin mediated increases in cAMP, but not
      receptor mediated increases in cAMP cause a rapid decrease in the affinity of
      MLCK for Ca(2+)/CaM.

PMID- 19403598
TI  - Stretch-stimulated glucose uptake in skeletal muscle is mediated by reactive
      oxygen species and p38 MAP-kinase.
AB  - Alternatives to the canonical insulin-stimulated pathway for glucose uptake are
      exercise- and exogenous reactive oxygen species (ROS)-stimulated glucose uptake.
      We proposed a model wherein mechanical loading, i.e. stretch, stimulates
      production of ROS to activate AMP-activated kinase (AMPK) to increase glucose
      uptake. Immunoblotting was used to measure protein phosphorylation; the
      fluorochrome probe 2'7'-dichlorofluorescin diacetate was used to measure
      cytosolic oxidant activity and 2-deoxy-d[1,2-(3)H]glucose was used to measure
      glucose uptake. The current studies demonstrate that stretch increases ROS,
      AMPKalpha phosphorylation and glucose transport in murine extensor digitorum
      longus (EDL) muscle (+121%, +164% and +184%, respectively; P < 0.05). We also
      demonstrate that stretch-induced glucose uptake persists in transgenic mice
      expressing an inactive form of the AMPKalpha2 catalytic subunit in skeletal
      muscle (+173%; P < 0.05). MnTBAP, a superoxide dismutase (SOD) mimetic, N-acteyl
      cysteine (NAC), a non-specific antioxidant, ebselen, a glutathione mimetic, or
      combined SOD plus catalase (ROS-selective scavengers) all decrease stretch
      stimulated glucose uptake (P < 0.05) without changing basal uptake (P > 0.16). We
      also demonstrate that stretch-stimulated glucose uptake persists in the presence
      of the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294001
      (P < 0.05) but is diminished by the p38-MAPK inhibitors SB203580 and A304000 (P >
      0.99). These data indicate that stretch-stimulated glucose uptake in skeletal
      muscle is mediated by a ROS- and p38 MAPK-dependent mechanism that appears to be
      AMPKalpha2- and PI3-K-independent.

PMID- 19403599
TI  - Relationship between nucleotide binding and ion channel gating in cystic fibrosis
      transmembrane conductance regulator.
AB  - We have employed rate-equilibrium free energy relationship (REFER) analysis to
      characterize the dynamic events involved in the allosteric regulation of cystic
      fibrosis transmembrane conductance regulator (CFTR) function. A wide range of
      different hydrolysable and poorly hydrolysable nucleoside triphosphates were used
      to elucidate the role of ATP hydrolysis in CFTR function. The linearity of the
      REFER plots and Phi values near unity for all ligands tested implies that CFTR
      channel gating is a reversible thermally driven process with all structural
      reorganization in the binding site(s) completed prior to channel opening. This is
      consistent with the requirement for nucleotide binding for channel opening.
      However, the channel structural transition from the open to the closed state
      occurs independently of any events in the binding sites. Similar results were
      obtained on substitution of amino acids at coupling joints between both
      nucleotide binding domains (NBD) and cytoplasmic loops (CL) in opposite halves of
      the protein, indicating that any structural reorganization there also had
      occurred in the channel closed state. The fact that fractional Phi values were
      not observed in either of these distant sites suggests that there may not be a
      deterministic 'lever-arm' mechanism acting between nucleotide binding sites and
      the channel gate. These findings favour a stochastic coupling between binding and
      gating in which all structural transitions are thermally driven processes. We
      speculate that increase of channel open state probability is due to reduction of
      the number of the closed state configurations available after physical
      interaction between ligand bound NBDs and the channel.

PMID- 19403600
TI  - Revisiting synaptic vesicle pool localization in the Drosophila neuromuscular
      junction.
AB  - The synaptic vesicles are organized in distinct populations or 'pools': the
      readily releasable pool (the first vesicles released upon stimulation), the
      recycling pool (which maintains release under moderate stimulation) and the
      reserve pool (which is called into action only upon strong, often unphysiological
      stimulation). A major question in the field is whether the pools consist of
      biochemically different vesicles or whether the pool tag is a spatial one (with
      the recycling vesicles found next to the release sites, and the reserve ones
      farther away). A strong and stable spatial segregation has been proposed in the
      last decade in the Drosophila larval neuromuscular junction--albeit based solely
      on light microscopy experiments. We have tested here this hypothesis using
      electron microscopy (EM) photoconversion. We found the recycling and reserve
      pools to be thoroughly intermixed at the EM level, indicating that spatial
      location is irrelevant for the functional properties of the vesicle.

PMID- 19403601
TI  - Deconstructing calsequestrin. Complex buffering in the calcium store of skeletal
      muscle.
AB  - Since its discovery in 1971, calsequestrin has been recognized as the main Ca(2+)
      binding protein inside the sarcoplasmic reticulum (SR), the organelle that stores
      and upon demand mobilizes Ca(2+) for contractile activation of muscle. This
      article reviews the potential roles of calsequestrin in excitation-contraction
      coupling of skeletal muscle. It first considers the quantitative demands for a
      structure that binds Ca(2+) inside the SR in view of the amounts of the ion that
      must be mobilized to elicit muscle contraction. It briefly discusses existing
      evidence, largely gathered in cardiac muscle, of two roles for calsequestrin: as
      Ca(2+) reservoir and as modulator of the activity of Ca(2+) release channels, and
      then considers the results of an incipient body of work that manipulates the
      cellular endowment of calsequestrin. The observations include evidence that both
      the Ca(2+) buffering capacity of calsequestrin in solution and that of the SR in
      intact cells decay as the free Ca(2+) concentration is lowered. Together with
      puzzling observations of increase of Ca(2+) inside the SR, in cells or vesicular
      fractions, upon activation of Ca(2+) release, this is interpreted as evidence
      that the Ca(2+) buffering in the SR is non-linear, and is optimized for support
      of Ca(2+) release at the physiological levels of SR Ca(2+) concentration. Such
      non-linearity of buffering is qualitatively explained by a speculation that puts
      together ideas first proposed by others. The speculation pictures calsequestrin
      polymers as 'wires' that both bind Ca(2+) and efficiently deliver it near the
      release channels. In spite of the kinetic changes, the functional studies reveal
      that cells devoid of calsequestrin are still capable of releasing large amounts
      of Ca(2+) into the myoplasm, consistent with the long term viability and apparent
      good health of mice engineered for calsequestrin ablation. The experiments
      therefore suggest that other molecules are capable of providing sites for
      reversible binding of large amounts of Ca(2+) inside the sarcoplasmic reticulum.

PMID- 19403602
TI  - Functional interactions between P2X4 and P2X7 receptors from mouse salivary
      epithelia.
AB  - Mouse parotid acinar cells express P2X4 and P2X7 receptors (mP2X4R and mP2X7R)
      whose physiological function remains undetermined. Here we show that mP2X4R
      expressed in HEK-293 cells do not allow the passage of tetraethylammonium (TEA+)
      and promote little, if any, ethidium bromide (EtBr) uptake when stimulated with
      ATP or BzATP. In contrast, mP2X7R generates slowly decaying TEA+ current,
      sustained Na+ current and promotes robust EtBr uptake. However, ATP-activated
      TEA+ current from acinar cells was unlike that generated by mP2X7R or mP2X4R.
      Functional interactions between mP2X4R and mP2X7R were investigated in HEK cells
      co-transfected with different mP2X4 : mP2X7 cDNA ratios and using solutions
      containing either TEA+ or Na+ ions. Co-expressed channels generated a TEA+
      current that displayed faster decay during ATP stimulation than mP2X7R alone.
      Moreover, cells transfected with a 2 : 1 cDNA ratio displayed decaying kinetics
      similar to those observed in acinar cells. Concentration-response curves in Na+
      containing solutions were constructed for heterologously expressed mP2X4R, mP2X7R
      and mP2X4R:mP2X7R co-expressions as well as acinar cells. The EC50 values
      determined were 11, 220, 434 and 442 microM, respectively. Na+ currents generated
      by expressing mP2X4R or mP2X7R alone were potentiated by ivermectin (IVM). In
      contrast, IVM potentiation in acinar cells and HEK cells co-expressing P2X4 and
      P2X7 (1 : 1 or 2 : 1 cDNA ratios) was seen only when the ATP concentration was
      lowered from 5 to 0.03 mM. Taken together our observations indicate a functional
      interaction between murine P2X7 and P2X4 receptors. Such interaction might occur
      in acinar cells to shape the response to extracellular ATP in salivary epithelia.

PMID- 19403603
TI  - Cation currents in human airway epithelial cells induced by infection with
      influenza A virus.
AB  - Influenza A viruses cause lung disease via an incompletely understood mechanism
      that involves the accumulation of liquid within the lungs. The accumulation of
      lung liquid is normally prevented by epithelial Na(+) absorption, a transport
      process regulated via several pathways including phosphoinositide-3-kinase
      (PI3K). Since the influenza A virus encodes a non-structural protein (NS1) that
      can activate this kinase, we now explore the effects of NS1 upon the biophysical
      properties of human airway epithelial cells. Transient expression of NS1
      depolarized electrically isolated cells maintained in glucocorticoid-free medium
      by activating a cation conductance identical to the glucocorticoid-induced
      conductance seen in single cells. This response involved PI3K-independent and
      PI3K-dependent mechanisms. Infecting glucocorticoid-deprived cells with influenza
      A virus disrupted the normal electrical coupling between neighbouring cells, but
      also activated a conductance identical to that induced by NS1. This response to
      virus infection was only partially dependent upon NS1-mediated activation of
      PI3K. The presence of NS1 allows influenza A to modify the biophysical properties
      of infected cells by activating a Na(+)-permeable conductance. Whilst the
      activation of Na(+)-permeable channels may be expected to increase the rate of
      Na(+) absorption and thus reduce the volume of liquid in the lung, liquid does
      normally accumulate in influenza A-infected lungs. The overall effect of
      influenza A on lung liquid volume may therefore reflect a balance between the
      activation and inhibition of Na(+)-permeable channels.

PMID- 19403604
TI  - Jugular venous overflow of noradrenaline from the brain: a neurochemical
      indicator of cerebrovascular sympathetic nerve activity in humans.
AB  - A novel neurochemical method was applied for studying the activity of sympathetic
      nerves in the human cerebral vascular system. The aim was to investigate whether
      noradrenaline plasma kinetic measurements made with internal jugular venous
      sampling reflect cerebrovascular sympathetic activity. A database was assembled
      of fifty-six healthy subjects in whom total body noradrenaline spillover
      (indicative of whole body sympathetic nervous activity), brain noradrenaline
      spillover and brain lipophlic noradrenaline metabolite (3,4-dihydroxyphenolglycol
      (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG)) overflow rates were measured.
      These measurements were also made following ganglion blockade (trimethaphan, n =
      6), central sympathetic inhibition (clonidine, n = 4) and neuronal noradrenaline
      uptake blockade (desipramine, n = 13) and in a group of patients (n = 9) with
      pure autonomic failure (PAF). The mean brain noradrenline spillover and brain
      noradrenaline metabolite overflow in healthy subjects were 12.5 +/- 1.8, and
      186.4 +/- 25 ng min(-1), respectively, with unilateral jugular venous sampling
      for both. Total body noradrenaline spillover was 605.8 ng min(-1) +/- 34.4 ng
      min(-1). As expected, trimethaphan infusion lowered brain noradrenaline spillover
      (P = 0.03), but perhaps surprisingly increased jugular overflow of brain
      metabolites (P = 0.01). Suppression of sympathetic nervous outflow with clonidine
      lowered brain noradrenaline spillover (P = 0.004), without changing brain
      metabolite overflow (P = 0.3). Neuronal noradrenaline uptake block with
      desipramine lowered the transcranial plasma extraction of tritiated noradrenaline
      (P = 0.001). The PAF patients had 77% lower brain noradrenaline spillover than
      healthy recruits (P = 0.06), indicating that in them sympathetic nerve
      degeneration extended to the cerebral circulation, but metabolites overflow was
      similar to healthy subjects (P = 0.3). The invariable discordance between
      noradrenline spillover and noradrenaline metabolite overflow from the brain under
      these different circumstances indicates that the two measures arise from
      different sources, i.e. noradrenaline spillover originates from the cerebral
      vasculature outside the blood-brain barrier, and the noradrenaline metabolites
      originate primarily from brain noradrenergic neurons. We suggest that
      measurements of transcranial plasma noradrenaline spillover have utility as a
      method for assessing the sympathetic nerve activity of the cerebral vasculature.

PMID- 19403605
TI  - Modulation of internal model formation during force field-induced motor learning
      by anodal transcranial direct current stimulation of primary motor cortex.
AB  - Human subjects can quickly adapt and maintain performance of arm reaching when
      experiencing novel physical environments such as robot-induced velocity-dependent
      force fields. Using anodal transcranial direct current stimulation (tDCS) this
      study showed that the primary motor cortex may play a role in motor adaptation of
      this sort. Subjects performed arm reaching movement trials in three phases: in a
      null force field (baseline), in a velocity-dependent force field (adaptation; 25
      N s m(-1)) and once again in a null force field (de-adaptation). Active or sham
      tDCS was directed to the motor cortex representation of biceps brachii muscle
      during the adaptation phase of the motor learning protocol. During the adaptation
      phase, the global error in arm reaching (summed error from an ideal trajectory)
      was similar in both tDCS conditions. However, active tDCS induced a significantly
      greater global reaching (overshoot) error during the early stage of de-adaptation
      compared to the sham tDCS condition. The overshoot error may be representative of
      the development of a greater predictive movement to overcome the expected imposed
      force. An estimate of the predictive, initial movement trajectory (signed error
      in the first 150 ms of movement) was significantly augmented during the
      adaptation phase with active tDCS compared to sham tDCS. Furthermore, this
      increase was linearly related to the change of the overshoot summed error in the
      de-adaptation process. Together the results suggest that anodal tDCS augments the
      development of an internal model of the novel adapted movement and suggests that
      the primary motor cortex is involved in adaptation of reaching movements of
      healthy human subjects.

PMID- 19403606
TI  - Minor sarcoplasmic reticulum membrane components that modulate excitation
      contraction coupling in striated muscles.
AB  - In striated muscle, activation of contraction is initiated by membrane
      depolarisation caused by an action potential, which triggers the release of
      Ca(2+) stored in the sarcoplasmic reticulum by a process called excitation
      contraction coupling. Excitation-contraction coupling occurs via a highly
      sophisticated supramolecular signalling complex at the junction between the
      sarcoplasmic reticulum and the transverse tubules. It is generally accepted that
      the core components of the excitation-contraction coupling machinery are the
      dihydropyridine receptors, ryanodine receptors and calsequestrin, which serve as
      voltage sensor, Ca(2+) release channel, and Ca(2+) storage protein, respectively.
      Nevertheless, a number of additional proteins have been shown to be essential
      both for the structural formation of the machinery involved in excitation
      contraction coupling and for its fine tuning. In this review we discuss the
      functional role of minor sarcoplasmic reticulum protein components. The
      definition of their roles in excitation-contraction coupling is important in
      order to understand how mutations in genes involved in Ca(2+) signalling cause
      neuromuscular disorders.

PMID- 19403608
TI  - Developmental regulation of the intracellular Ca2+ sensitivity of vesicle fusion
      and Ca2+-secretion coupling at the rat calyx of Held.
AB  - Developmental refinement of synaptic transmission can occur via changes in
      several pre- and postsynaptic factors, but it has been unknown whether the
      intrinsic Ca2+ sensitivity of vesicle fusion in the nerve terminal can be
      regulated during development. Using the calyx of Held, a giant synapse in the
      auditory pathway, we studied the presynaptic mechanisms underlying the
      developmental regulation of Ca2+-secretion coupling, comparing a time period
      before, and shortly after the onset of hearing in rats. We found an approximately
      2-fold leftward shift in the relationship between EPSC amplitude and presynaptic
      Ca2+ current charge (QCa), indicating that brief presynaptic Ca2+ currents become
      significantly more efficient in driving release. Using a Ca2+ tail current
      protocol, we also found that the high cooperativity between EPSC amplitude and
      QCa was slightly reduced with development. In contrast, in presynaptic Ca2+
      uncaging experiments, the intrinsic Ca2+ cooperativity of vesicle fusion was
      identical, and the intrinsic Ca2+ sensitivity was slightly reduced with
      development. This indicates that the significantly enhanced release efficiency of
      brief Ca2+ currents must be caused by a tighter co-localization of Ca2+ channels
      and readily releasable vesicles, but not by changes in the intrinsic properties
      of Ca2+-dependent release. Using the parameters of the intrinsic Ca2+ sensitivity
      measured at each developmental stage, we estimate that during a presynaptic
      action potential (AP), a given readily releasable vesicle experiences an about
      1.3-fold higher 'local' intracellular Ca2+ concentration ([Ca2+]i) signal with
      development. Thus, the data indicate a tightening in the Ca2+ channel-vesicle co
      localization during development, without a major change in the intrinsic Ca2+
      sensitivity of vesicle fusion.

PMID- 19403607
TI  - Junctin and the histidine-rich Ca2+ binding protein: potential roles in heart
      failure and arrhythmogenesis.
AB  - Contractile dysfunction and ventricular arrhythmias associated with heart failure
      have been attributed to aberrant sarcoplasmic reticulum (SR) Ca(2+) cycling. The
      study of junctin (JCN) and histidine-rich Ca(2+) binding protein (HRC) becomes of
      particular importance since these proteins have been shown to be critical
      regulators of Ca(2+) cycling. Specifically, JCN is a SR membrane protein, which
      is part of the SR Ca(2+) release quaternary structure that also includes the
      ryanodine receptor, triadin and calsequestrin. Functionally, JCN serves as a
      bridge between calsequestrin and the Ca(2+) release channel, ryanodine receptor.
      HRC is a SR luminal Ca(2+) binding protein known to associate with both triadin
      and the sarcoplasmic reticulum Ca(2+)-ATPase, and may thus mediate the crosstalk
      between SR Ca(2+) uptake and release. Indeed, evidence from genetic models of JCN
      and HRC indicate that they are important in cardiophysiology as alterations in
      these proteins affect SR Ca(2+) handling and cardiac function. In addition,
      downregulation of JCN and HRC may contribute to Ca(2+) cycling perturbations
      manifest in the failing heart, where their protein levels are significantly
      reduced. This review examines the roles of JCN and HRC in SR Ca(2+) cycling and
      their potential significance in heart failure.

PMID- 19403609
TI  - Mast cell-cholinergic nerve interaction in mouse airways.
AB  - We addressed the mechanism by which antigen contracts trachea isolated from
      actively sensitized mice. Trachea were isolated from mice (C57BL/6J) that had
      been actively sensitized to ovalbumin (OVA). OVA (10 microg ml(-1)) caused
      histamine release (approximately total tissue content), and smooth muscle
      contraction that was rapid in onset and short-lived (t(1/2) < 1 min), reaching
      approximately 25% of the maximum tissue response. OVA contraction was mimicked by
      5-HT, and responses to both OVA and 5-HT were sensitive to 10 microm-ketanserin
      (5-HT(2) receptor antagonist) and strongly inhibited by atropine (1microm).
      Epithelial denudation had no effect on the OVA-induced contraction. Histological
      assessment revealed about five mast cells/tracheal section the vast majority of
      which contained 5-HT. There were virtually no mast cells in the mast cell
      deficient (sash -/-) mouse trachea. OVA failed to elicit histamine release or
      contractile responses in trachea isolated from sensitized mast cell-deficient
      (sash -/-) mice. Intracellular recordings of the membrane potential of
      parasympathetic neurons in mouse tracheal ganglia revealed a ketanserin-sensitive
      5-HT-induced depolarization and similar depolarization in response to OVA
      challenge. These data support the hypothesis that antigen-induced contraction of
      mouse trachea is epithelium-independent, and requires mast cell-derived 5-HT to
      activate 5-HT(2) receptors on parasympathetic cholinergic neurons. This leads to
      acetylcholine release from nerve terminals, and airway smooth muscle contraction.

PMID- 19403611
TI  - NMDA potentiation by visible light in the presence of a fluorescent neurosteroid
      analogue.
AB  - N-Methyl-D-aspartate (NMDA) receptors are widely studied because of their
      importance in synaptic plasticity and excitotoxic cell death. Here we report a
      novel method of potentiating NMDA receptors with fluorescence excited by blue
      (480 nm) light. In the presence of 300 nM of a (7-nitro-2,1,3-benzoxadiazol-4-yl)
      amino (NBD)-tagged neuroactive steroid carrier C2-NBD-(3alpha,5alpha)-3
      hydroxypregnan-20-one (C2-NBD 3alpha5alphaP), responses of cultured hippocampal
      neurons to 10 microM NMDA were potentiated to 219.2 +/- 9.2% of the baseline
      response (100%) by a 30 s exposure to 480 nm light. The potentiation decayed back
      to baseline with a time constant of 80.6 s. Responses to 1 microM and 100 microM
      NMDA were potentiated to 147.9 +/- 9.6% and 174.1 +/- 15.6% of baseline,
      respectively, suggesting that visible-light potentiation is relatively
      insensitive to NMDA concentration. Peak autaptic NMDA responses were potentiated
      to 178.9 +/- 22.4% of baseline. Similar potentiation was seen with 10 microM NBD
      lysine, suggesting that visible-light potentiation is not a steroid effect.
      Potentiation was also seen with a steroid analogue in which the NBD was replaced
      with fluorescein, suggesting that NBD is not the only fluorophore capable of
      supporting visible-light potentiation. UV light and redox potentiation of NMDA
      receptors largely occluded subsequent blue light potentiation (127.7 +/- 7.4% and
      120.2 +/- 6.2% of baseline, respectively). The NR1a(C744A,C798A) mutant that is
      insensitive to redox and UV potentiation was also largely unaffected by visible
      light potentiation (135.0 +/- 10.0% of baseline). Finally, we found that the
      singlet oxygen scavenger furfuryl alcohol decreased visible-light potentiation.
      Collectively, these data suggest that visible-light potentiation of NMDA
      receptors by fluorescence excitation shares mechanisms with UV and redox
      potentiation and may involve singlet oxygen production.

PMID- 19403612
TI  - Altered firing pattern of single-unit muscle sympathetic nerve activity during
      handgrip exercise in chronic heart failure.
AB  - Sympathetic activation in chronic heart failure (CHF) is greatly augmented at
      rest but the response to exercise remains controversial. We previously
      demonstrated that single-unit muscle sympathetic nerve activity (MSNA) provides a
      more detailed description of the sympathetic response to physiological stress
      than multi-unit nerve recordings. The purpose of this study was to determine
      whether the reflex response and discharge properties of single-unit MSNA are
      altered during handgrip exercise (HG, 30% of maximum voluntary contraction for 3
      min) in CHF patients (New York Heart Association functional class II or III, n =
      16) compared with age-matched healthy control subjects (n = 13). At rest, both
      single-unit and multi-unit indices of sympathetic outflow were augmented in CHF
      compared with controls (P < 0.05). However, the percentage of cardiac intervals
      that contained one, two, three or four single-unit spikes were not different
      between the groups. Compared to the control group, HG elicited a larger increase
      in multi-unit total MSNA (Delta1002 +/- 50 compared with Delta636 +/- 76 units
      min(-1), P < 0.05) and single-unit MSNA spike incidence (Delta27 +/- 5 compared
      with Delta8 +/- 2 spikes (100 heart beats)(-1)), P < 0.01) in the CHF patients.
      More importantly, the percentage of cardiac intervals that contained two or three
      single-unit spikes was increased (P < 0.05) during exercise in the CHF group only
      (Delta8 +/- 2% and Delta5 +/- 1% for two and three spikes, respectively). These
      results suggest that the larger multi-unit total MSNA response observed during HG
      in CHF is brought about in part by an increase in the probability of multiple
      firing of single-unit sympathetic neurones.

PMID- 19403613
TI  - Separate signalling mechanisms underlie mGluR1 modulation of leak channels and
      NMDA receptors in the network underlying locomotion.
AB  - Metabotropic glutamate receptor subtype 1 (mGluR1) contributes importantly to the
      activity of the spinal locomotor network. For example, it potentiates NMDA
      current and inhibits leak conductance in lamprey spinal cord neurons. In this
      study we examined the signalling pathways underlying the mGluR1 modulation of
      NMDA receptors and leak channels, respectively. Our results show that mGluR1
      induced potentiation of NMDA current required activation of phospholipase C (PLC)
      and was independent of the increase in the intracellular Ca2+ concentration
      because it was unaffected by the Ca2+ chelator BAPTA and by depletion of the
      internal Ca2+ stores with thapsigargin. We also show that the mGluR1-mediated
      inhibition of leak channels is mediated by activation of G-proteins. Finally, we
      show that blockade of protein kinase C (PKC) abolished the mGluR1-induced
      inhibition of leak current without affecting the potentiation of NMDA receptors.
      The contribution of mGluR1-mediated modulation of leak channels to the
      potentiation of the locomotor cycle frequency was assessed during fictive
      locomotion. Blockade of PKC significantly decreased the short-term potentiation
      of locomotor cycle frequency by mGluR1. These results show that the effects of
      mGluR1 activation on the two cellular targets, the NMDA receptor and leak
      channels, are mediated through separate signalling pathways.

PMID- 19403614
TI  - Organizational role for pubertal androgens on adult hypothalamic-pituitary
      adrenal sensitivity to testosterone in the male rat.
AB  - The inhibitory effect of androgens on the hypothalamic-pituitary-adrenal (HPA)
      axis in basal and stress conditions in adult male rats is well documented. Major
      sex-related neuroendocrine changes take place during puberty. There is a robust
      rise in production and secretion of gonadal steroids, which is thought to
      underlie numerous neural and behavioural changes brought on after puberty. The
      present study investigated the effect of the pubertal rise in gonadal steroid
      levels on the subsequent adult corticosterone profile, particularly the
      sensitivity of the adult HPA axis to testosterone. Animals were castrated either
      prepubertally (28 days) or in adulthood (11 weeks) and adult animals were
      subsequently treated with subcutaneous implants containing either testosterone or
      cholesterol. Using an automated blood sampling system, blood was collected from
      each freely moving, conscious rat every 10 min (i) over a 24 h period; (ii) in
      response to 10 min of noise stress, and (iii) following an immunological
      challenge with lipopolysaccharide (LPS). Analysis revealed that testosterone
      treatment did not significantly affect overall corticosterone release over the 24
      h period in adult animals castrated before puberty in contrast to animals
      castrated in adulthood in which testosterone significantly suppressed
      corticosterone secretion. Following either a noise stress or LPS injection,
      testosterone treatment did not affect the hypothalamic or adrenal stress response
      in animals castrated prepubertally. Testosterone significantly suppressed the
      corticotrophin-releasing hormone and arginine vasopressin mRNA as well as the
      corticosterone response to LPS in castrated animals that had had their testes
      intact over puberty. These data provide evidence that puberty is a critical
      organizational period during which rising levels of gonadal steroids programme
      the sensitivity of the adult HPA axis to gonadal steroids in adulthood.

PMID- 19403615
TI  - Decreased microvascular vasomotion and myogenic response in rat skeletal muscle
      in association with acute insulin resistance.
AB  - In addition to increased glucose uptake, insulin action is associated with
      increased total and microvascular blood flow, and vasomotion in skeletal muscle.
      The aim of this study was to determine the effect of acute insulin resistance
      caused by the peripheral vasoconstrictor alpha-methylserotonin (alphaMT) on
      microvascular vasomotion in muscle. Heart rate (HR), mean arterial pressure
      (MAP), femoral blood flow (FBF), whole body glucose infusion (GIR) and hindleg
      glucose uptake (HGU) were determined during control and hyperinsulinaemic
      euglycaemic clamp conditions in anaesthetized rats receiving alphaMT infusion.
      Changes in muscle microvascular perfusion were measured by laser Doppler
      flowmetry (LDF) and vasomotion was assessed by applying wavelet analysis to the
      LDF signal. Insulin increased GIR and HGU. Five frequency bands corresponding to
      cardiac, respiratory, myogenic, neurogenic and endothelial activities were
      detected in the LDF signal. Insulin infusion alone increased FBF (1.18 +/- 0.10
      to 1.78 +/- 0.12 ml min(-1), P < 0.05), LDF signal strength (by 16% compared to
      baseline) and the relative amplitude of the myogenic component of vasomotion
      (0.89 +/- 0.09 to 1.18 +/- 0.06, P < 0.05). When infused alone alphaMT decreased
      LDF signal strength and the myogenic component of vasomotion by 23% and 27%
      respectively compared to baseline, but did not affect HGU or FBF. Infusion of
      alphaMT during the insulin clamp decreased the stimulatory effects of insulin on
      GIR, HGU, FBF and LDF signal and blocked the myogenic component of vasomotion.
      These data suggest that insulin action to recruit microvascular flow may in part
      involve action on the vascular smooth muscle to increase vasomotion in skeletal
      muscle to thereby enhance perfusion and glucose uptake. These processes are
      impaired with this model of alphaMT-induced acute insulin resistance.

PMID- 19403616
TI  - Opioid receptor mechanisms at the hypoglossal motor pool and effects on tongue
      muscle activity in vivo.
AB  - Opioids can modulate breathing and predispose to respiratory depression by
      actions at various central nervous system sites, but the mechanisms operating at
      respiratory motor nuclei have not been studied. This study tests the hypotheses
      that (i) local delivery of the mu-opioid receptor agonist fentanyl into the
      hypoglossal motor nucleus (HMN) will suppress genioglossus activity in vivo, (ii)
      a component of this suppression is mediated by opioid-induced acetylcholine
      release acting at muscarinic receptors, and (iii) delta- and kappa-opioid
      receptors also modulate genioglossus activity. Seventy-two isoflurane
      anaesthetised, tracheotomised, spontaneously breathing rats were studied during
      microdialysis perfusion into the HMN of (i) fentanyl and naloxone (mu-opioid
      receptor antagonist), (ii) fentanyl with and without co-application of muscarinic
      receptor antagonists, and (iii) delta- and kappa-opioid receptor agonists and
      antagonists. The results showed (i) that fentanyl at the HMN caused a suppression
      of genioglossus activity (P < 0.001) that reversed with naloxone (P < 0.001),
      (ii) that neither atropine nor scopolamine affected the fentanyl-induced
      suppression of genioglossus activity, and (iii) that delta-, but not kappa-,
      opioid receptor stimulation also suppressed genioglossus activity (P = 0.036 and
      P = 0.402 respectively). We conclude that mu-opioid receptor stimulation
      suppresses motor output from a central respiratory motoneuronal pool that
      activates genioglossus muscle, and this suppression does not involve muscarinic
      receptor-mediated inhibition. This mu-opioid receptor-induced suppression of
      tongue muscle activity by effects at the hypoglossal motor pool may underlie the
      clinical concern regarding adverse upper airway function with mu-opioid
      analgesics. The inhibitory effects of mu- and delta-opioid receptors at the HMN
      also indicate an influence of endogenous enkephalins and endorphins in
      respiratory motor control.

PMID- 19403617
TI  - Postnatal early overnutrition changes the leptin signalling pathway in the
      hypothalamic-pituitary-thyroid axis of young and adult rats.
AB  - Postnatal early overnutrition (EO) is a risk factor for obesity in adult life.
      Rats raised in a small litter can develop hyperinsulinaemia, hyperphagia,
      hyperleptinaemia and hypertension as adults. Since leptin regulates the
      hypothalamic-pituitary-thyroid axis and the metabolism of thyroid hormones, we
      studied the leptin signalling pathway in pituitary and thyroid glands of the
      postnatal EO model. To induce EO, at the third day of lactation the litter size
      was reduced to three pups per litter (SL group). In control litters (NL group),
      the litter size was adjusted to 10 pups per litter. Body weight and food intake
      were monitored. Rat offspring were killed at 21 (weaning) and 180 days old
      (adulthood). Plasma thyroid hormones, thyroid-stimulating hormone (TSH) and
      leptin were measured by radioimmunoassay. Proteins of the leptin signalling
      pathway were analysed by Western blotting. Body weight of offspring in the SL
      group was higher from the seventh day of lactation (+33%, P < 0.05) until 180
      days old (+18%, P < 0.05). Offspring in the SL group showed higher visceral fat
      mass at 21 and 180 days old (+176 and +52%, respectively, P < 0.05), but plasma
      leptin was higher only at 21 days (+88%, P < 0.05). The SL offspring showed
      higher plasma TSH, 3,5,3'-triiodothronine (T(3)) and thyroxine (T(4)) at 21 days
      (+60, +91 and +68%, respectively, P < 0.05), while the opposite was observed at
      180 days regarding thyroid hormones (T(3), -10%; and T(4), -30%, P < 0.05), with
      no difference in TSH levels. In hypothalamus, no change was observed in the
      leptin signalling pathway at 21 days. However, lower janus thyrosine kinase 2
      (JAK2) and phosphorilated-signal transducer and activator of transcription-3 (p
      STAT3) content were detected in adulthood. In pituitary, the SL group presented
      higher leptin receptors (Ob-R), JAK2 and p-STAT3 content at 21 days and lower
      JAK2 and STAT3 content at 180 days old. In contrast, in thyroid, the Ob-R
      expression was lower in young SL rats, while the adult SL group presented higher
      Ob-R and JAK2 content. We showed that postnatal EO induces short- and long-term
      effects upon the hypothalamic-pituitary-thyroid axis. These changes may help to
      explain future development of metabolic and endocrine dysfunctions, such as
      metabolic syndrome and hypothyroidism.

PMID- 19403618
TI  - Tumour necrosis factor alpha activates nuclear factor kappaB signalling to reduce
      N-type voltage-gated Ca2+ current in postganglionic sympathetic neurons.
AB  - Inflammation has profound effects on the innervation of affected tissues,
      including altered neuronal excitability and neurotransmitter release. As Ca(2+)
      influx through voltage-gated Ca(2+) channels (VGCCs) is a critical determinant of
      excitation-secretion coupling in nerve terminals, the aim of this study was to
      characterize the effect of overnight incubation in the inflammatory mediator
      tumour necrosis factor alpha (TNFalpha; 1 nM) on VGCCs in dissociated neurons
      from mouse superior mesenteric ganglia (SMG). Voltage-gated Ca(2+) currents
      (I(Ca)) were measured using the perforated patch clamp technique and the VGCC
      subtypes present in SMG neurons were estimated based on inhibition by selective
      VGCC blockers: omega-conotoxin GVIA (300 nM; N-type), nifedipine (10 microM; L
      type), and omega-conotoxin MVIIC (300 nM; N-, P/Q-type). We used intracellular
      Ca(2+) imaging with Fura-2 AM to compare Ca(2+) influx during depolarizations in
      control and TNFalpha-treated neurons. TNF receptor and VGCC mRNA expression were
      measured using PCR, and channel alpha subunit (CaV2.2) was localized with
      immunohistochemistry. Incubation in TNFalpha significantly decreased I(Ca)
      amplitude and depolarization-induced Ca(2+) influx. The reduction in I(Ca) was
      limited to omega-conotoxin GVIA-sensitive N-type Ca(2+) channels. Depletion of
      glial cells by incubation in cytosine arabinoside (5 microM) did not affect I(Ca)
      inhibition by TNFalpha. Preincubation of neurons with SC-514 (20 microM) or BAY
      11-7082 (1 microM), which both inhibit nuclear factor kappaB signalling,
      prevented the reduction in I(Ca) by TNFalpha. Inhibition of N-type VGCCs
      following TNFalpha incubation was associated with a decrease in CaV2.2 mRNA and
      reduced membrane localization of CaV2.2 immunoreactivity. These data suggest that
      TNFalpha inhibits I(Ca) in SMG neurons and identify a novel role for NF-kappaB in
      the regulation of neurotransmitter release during inflammatory conditions with
      elevated circulating TNFalpha, such as Crohn's disease and Guillain-Barre
      syndrome.

PMID- 19403619
TI  - Direct evidence of nitric oxide release from neuronal nitric oxide synthase
      activation in the left ventricle as a result of cervical vagus nerve stimulation.
AB  - Information regarding vagal innervation in the cardiac ventricle is limited and
      the direct effect of vagal stimulation on ventricular myocardial function is
      controversial. We have recently provided indirect evidence that the anti
      fibrillatory effect of vagus nerve stimulation on the ventricle is mediated by
      nitric oxide (NO). The aim of this study was to provide direct evidence for the
      release of nitric oxide in the cardiac ventricle during stimulation of the
      efferent parasympathetic fibres of the cervical vagus nerve. The isolated
      innervated rabbit heart was employed with the use of the NO fluorescent indicator
      4,5-diaminofluorescein diacetate (DAF-2 DA) during stimulation of the cervical
      vagus nerves and acetylcholine perfusion in the absence and presence of the non
      specific NO synthase inhibitor NG-nito-L-arginine (L-NNA) and the neuronal NO
      synthase selective inhibitor 1-(2-trifluormethylphenyl)imidazole (TRIM). Using
      the novel fluorescence method in the beating heart, we have shown that NO
      dependent fluorescence is increased by 0.92 +/- 0.26, 1.20 +/- 0.30 and 1.91 +/-
      0.27% (during low, medium and high frequency, respectively) in the ventricle in a
      stimulation frequency-dependent manner during vagus nerve stimulation, with
      comparable increases seen during separate stimulation of the left and right
      cervical vagus nerves. Background fluorescence is reduced during perfusion with L
      NNA and the increase in fluorescence during high frequency vagal stimulation is
      inhibited during perfusion with both L-NNA (1.97 +/- 0.35% increase before L-NNA,
      0.00 +/- 0.02% during L-NNA) and TRIM (1.78 +/- 0.18% increase before TRIM, -0.11
      +/- 0.08% during TRIM). Perfusion with 0.1 microM acetylcholine increased NO
      fluorescence by 0.76 +/- 0.09% which was blocked by L-NNA (change of 0.00 +/-
      0.03%) but not TRIM (increase of 0.82 +/- 0.21%). Activation of cardiac
      parasympathetic efferent nerve fibres by stimulation of the cervical vagus is
      associated with NO production and release in the ventricle of the rabbit, via the
      neuronal isoform of nitric oxide synthase.

PMID- 19403620
TI  - Mechanisms underlying short-term modulation of transmitter release by presynaptic
      depolarization.
AB  - Presynaptic terminal depolarization modulates the efficacy of transmitter
      release. Residual Ca2+ remaining after presynaptic depolarization is thought to
      play a critical role in facilitation of transmitter release, but its downstream
      mechanism remains unclear. By making simultaneous pre- and postsynaptic
      recordings at the rodent calyx of Held synapse, we have investigated mechanisms
      involved in the facilitation and depression of postsynaptic currents induced by
      presynaptic depolarization. In voltage-clamp experiments, cancellation of the
      Ca2+-dependent presynaptic Ca2+ current (I(pCa)) facilitation revealed that this
      mechanism can account for 50% of postsynaptic current facilitation, irrespective
      of intraterminal EGTA concentrations. Intraterminal EGTA, loaded at 10 mM, failed
      to block postsynaptic current facilitation, but additional BAPTA at 1 mM
      abolished it. Potassium-induced sustained depolarization of non-dialysed
      presynaptic terminals caused a facilitation of postsynaptic currents,
      superimposed on a depression, with the latter resulting from reductions in
      presynaptic action potential amplitude and number of releasable vesicles. We
      conclude that presynaptic depolarization bidirectionally modulates transmitter
      release, and that the residual Ca2+ mechanism for synaptic facilitation operates
      in the immediate vicinity of voltage-gated Ca2+ channels in the nerve terminal.

PMID- 19403621
TI  - Improved in vivo two-photon imaging after blood replacement by perfluorocarbon.
AB  - Two-photon microscopy is a powerful method in biomedical research that allows
      functional and anatomical imaging at a subcellular resolution in vivo. The
      technique is seriously hampered by absorption and scattering of light by blood,
      which prevents imaging through large vessels. Here, we demonstrate in the rat
      cerebral cortex that blood replacement by perfluorocarbon emulsion, a compound
      also used in human critical care medicine, yields superior image quality, while
      preserving neuronal integrity. Shadows of large superficial vessels disappear
      completely and cells can be imaged underneath them. For the first time, it is
      possible to image complete populations of neurons and astrocytes in the upper
      layers of neocortex in vivo.

PMID- 19403622
TI  - Properties of Orai1 mediated store-operated current depend on the expression
      levels of STIM1 and Orai1 proteins.
AB  - Two cellular proteins, stromal interaction molecule 1 (STIM1) and Orai1, are
      recently discovered essential components of the Ca2+ release activated Ca2+
      (CRAC) channel. Orai1 polypeptides form the pore of the CRAC channel, while STIM1
      plays the role of the endoplasmic reticulum Ca2+ sensor required for activation
      of CRAC current (I(CRAC)) by store depletion. It is not known, however, if the
      role of STIM1 is limited exclusively to Ca2+ sensing, or whether interaction
      between Orai1 and STIM1, either direct or indirect, also defines the properties
      of I(CRAC). In this study we investigated how the relative expression levels of
      ectopic Orai1 and STIM1 affect the properties of I(CRAC). The results show that
      cells expressing low Orai1 : STIM1 ratios produce I(CRAC) with strong fast Ca2+
      dependent inactivation, while cells expressing high Orai1 : STIM1 ratios produce
      I(CRAC) with strong activation at negative potentials. Moreover, the expression
      ratio of Orai1 and STIM1 affects Ca2+, Ba2+ and Sr2+ conductance, but has no
      effect on the current in the absence of divalent cations. The results suggest
      that several key properties of Ca2+ channels formed by Orai1 depend on its
      interaction with STIM1, and that the stoichiometry of this interaction may vary
      depending on the relative expression levels of these proteins.

PMID- 19403623
TI  - Triadin: what possible function 20 years later?
AB  - During the last 20 years, the identification of triadin function in cardiac and
      skeletal muscle has been the focus of numerous studies. First thought of as the
      missing link between the ryanodine receptor and the dihydropyridine receptor and
      responsible of skeletal type excitation-contraction coupling, the current
      hypothesis on triadin function has slowly evolved, and triadin is envisaged now
      as a regulator of calcium release, both in cardiac and skeletal muscle.
      Nevertheless, none of the experiments performed up to now has given a clear cut
      view of what triadin really does in muscle. The problem became more complex with
      the identification of multiple triadin isoforms, having possibly multiple
      functions. Using a different approach from what has been done previously, we have
      obtained new clues about the function of triadin. Our data point to a possible
      involvement of triadin in reticulum structure, in relation with the microtubule
      network.

PMID- 19403624
TI  - The changing balance of brainstem-spinal cord modulation of pain processing over
      the first weeks of rat postnatal life.
AB  - Brainstem-spinal cord connections play an essential role in adult pain
      processing, and the modulation of spinal pain network excitability by brainstem
      nuclei is known to contribute to hyperalgesia and chronic pain. Less well
      understood is the role of descending brainstem pathways in young animals when
      pain networks are more excitable and exposure to injury and stress can lead to
      permanent modulation of pain processing. Here we show that up to postnatal day 21
      (P21) in the rat, the rostroventral medulla of the brainstem (RVM) exclusively
      facilitates spinal pain transmission but that after this age (P28 to adult), the
      influence of the RVM shifts to biphasic facilitation and inhibition. Graded
      electrical microstimulation of the RVM at different postnatal ages revealed a
      robust shift in the balance of descending control of both spinal nociceptive
      flexion reflex EMG activity and individual dorsal horn neuron firing properties,
      from excitation to inhibition, beginning after P21. The shift in polarity of
      descending control was also observed following excitotoxic lesions of the RVM in
      adult and P21 rats. In adults, RVM lesions decreased behavioural mechanical
      sensory reflex thresholds, whereas the same lesion in P21 rats increased
      thresholds. These data demonstrate, for the first time, the changing postnatal
      influence of the RVM in spinal nociception and highlight the central role of
      descending brainstem control in the maturation of pain processing.

PMID- 19403625
TI  - Pivotal Advance: Expansion of small sputum macrophages in CF: failure to express
      MARCO and mannose receptors.
AB  - Macrophages in the airways form an important element of immune defense and
      inflammation. We analyzed induced sputum from airways of patients with CF for the
      types of macrophages present, their receptor expression, and phagocytic function.
      In samples from patients and age-matched controls, macrophages were analyzed by
      multicolor flow cytometry, scavenger receptor expression was studied at the
      protein and mRNA level, and receptor function was investigated using fluorescent
      particles. In adult patients with CF, we discovered a pronounced expansion of the
      small CD14+ DR+ CD68weak+ macrophages to 73 +/- 18% compared with 16 +/- 8% in
      healthy controls. Expression of the MARCO and CD206 (mannose receptor) was
      strongly reduced at the mRNA and protein level in sputum macrophages. Antibody
      blocking studies showed that MARCO mediates phagocytosis of unopsonized
      particles. In line with reduced MARCO expression, sputum macrophages in CF showed
      a deficient uptake of particles (23+/-9% of cells) compared with healthy controls
      (71+/-15%). The deficiency of MARCO expression in the predominant small sputum
      macrophages in CF may lead to impaired clearance of inhaled particles with
      increased inflammation and damage to the CF lung.

PMID- 19403627
TI  - The birds and the bees: pollinator behaviour and variation in the mating system
      of the rare shrub Grevillea macleayana.
AB  - BACKGROUND AND AIMS: In Australia, honey-bees have invaded systems that evolved
      without social insect pollinators, where many plants are adapted to vertebrate
      pollination. Behavioural differences between pollinators are likely to influence
      mating patterns, but few studies have examined this empirically in long-lived,
      woody, perennials. It was shown previously that outcrossing rates in Grevillea
      macleayana vary among populations. Here tests were conducted to determine whether
      the behaviour of birds and honey-bees differed between a population previously
      found to be highly outcrossed and two inbreeding populations. METHODS: Visit
      frequencies and movement patterns of the visitors to inflorescences at three
      sites over two seasons were compared. A caging experiment was used to test the
      effects of excluding birds on pollen removal from newly opened flowers and on
      pollen deposition on stigmas that had been washed clean. KEY RESULTS: Honey-bees
      were the most frequent visitors overall, but honeyeaters were more frequent
      visitors in the population previously found to have a high outcrossing rate than
      they were in either of the other populations. More visits by honeyeaters were
      from distant plants. Pollen removal did not vary greatly among sites, and was not
      affected by bird exclusion; however, more pollen was deposited on the stigmas of
      cleaned pollen presenters in the population previously observed to be highly
      outcrossing than in the other two. This high level of pollen deposition was
      reduced by experimental bird exclusion. CONCLUSIONS: Honey-bees were the most
      frequent visitors, by an order of magnitude, and excluding vertebrates revealed
      that bees were removing most of the pollen but deposited fewer pollen grains on
      stigmas. Birds were more frequent visitors at the site previously found to be
      outcrossing than the other two sites, and they moved further between plants and
      visited fewer inflorescences on a plant during a foraging bout than bees did.
      These characteristics of bird visits to G. macleayana would be sufficient to
      produce significant variation in outcrossing rates among sites.

PMID- 19403626
TI  - Different genome-specific chromosome stabilities in synthetic Brassica
      allohexaploids revealed by wide crosses with Orychophragmus.
AB  - BACKGROUND AND AIMS: In sexual hybrids between cultivated Brassica species and
      another crucifer, Orychophragmus violaceus (2n = 24), parental genome separation
      during mitosis and meiosis is under genetic control but this phenomenon varies
      depending upon the Brassica species. To further investigate the mechanisms
      involved in parental genome separation, complex hybrids between synthetic
      Brassica allohexaploids (2n = 54, AABBCC) from three sources and O. violaceus
      were obtained and characterized. METHODS: Genomic in situ hybridization,
      amplified fragment length polymorphism (AFLP) and single-strand conformation
      polymorphism (SSCP) were used to explore chromosomal/genomic components and rRNA
      gene expression of the complex hybrids and their progenies. KEY RESULTS: Complex
      hybrids with variable fertility exhibited phenotypes that were different from the
      female allohexaploids and expressed some traits from O. violaceus. These hybrids
      were mixoploids (2n = 34-46) and retained partial complements of allohexaploids,
      including whole chromosomes of the A and B genomes and some of the C genome but
      no intact O. violaceus chromosomes; AFLP bands specific for O. violaceus, novel
      for two parents and absent in hexaploids were detected. The complex hybrids
      produced progenies with chromosomes/genomic complements biased to B. juncea (2n =
      36, AABB) and novel B. juncea lines with two genomes of different origins. The
      expression of rRNA genes from B. nigra was revealed in all allohexaploids and
      complex hybrids, showing that the hierarchy of nucleolar dominance (B. nigra, BB
      > B. rapa, AA > B. oleracea, CC) in Brassica allotetraploids was still valid in
      these plants. CONCLUSIONS: The chromosomes of three genomes in these synthetic
      Brassica allohexaploids showed different genome-specific stabilities (B > A > C)
      under induction of alien chromosome elimination in crosses with O. violaceus,
      which was possibly affected by nucleolar dominance.

PMID- 19403628
TI  - How large is the energy gap that accounts for the obesity epidemic?

PMID- 19403629
TI  - Polymorphisms in uracil-processing genes, but not one-carbon nutrients, are
      associated with altered DNA uracil concentrations in an urban Puerto Rican
      population.
AB  - BACKGROUND: Five genes--UNG, SMUG1, MBD4, TDG, and DUT--are involved in the
      repair or prevention of uracil misincorporation into DNA, an anomaly that can
      cause mutagenic events that lead to cancer. Little is known about the
      determinants of uracil misincorporation, including the effects of single
      nucleotide polymorphisms (SNPs) in the abovementioned genes. Because of their
      metabolic function, folate and other one-carbon micronutrients may be important
      factors in the control of uracil misincorporation. OBJECTIVES: We sought to
      identify polymorphisms in uracil-processing genes that are determinants of DNA
      uracil concentration and to establish whether one-carbon nutrient status can
      further modify their effects. DESIGN: We examined the relations between 23
      selected variants in the 5 uracil-processing genes, uracil concentrations in
      whole-blood DNA, and one-carbon nutrient (folate, vitamins B-6 and B-12, and
      riboflavin) status in 431 participants of the Boston Puerto Rican Health Study.
      RESULTS: Four SNPs in DUT, UNG, and SMUG1 showed a significant association with
      DNA uracil concentration. The SNPs in SMUG1 (rs2029166 and rs7296239) and UNG
      (rs34259) were associated with increased uracil concentrations in the variant
      genotypes (P = 0.011, 0.022, and 0.045, respectively), whereas the DUT SNP
      (rs4775748) was associated with a decrease (P = 0.023). In this population, one
      carbon nutrient status was not associated with DNA uracil concentration, and it
      did not modify the effect of these 4 identified SNPs. CONCLUSION: Because
      elevated uracil misincorporation may induce mutagenic lesions, possibly leading
      to cancer, we propose that the 4 characterized SNPs in DUT, UNG, and SMUG1 may
      influence cancer risk and therefore deserve further investigation.

PMID- 19403630
TI  - The effect of n-3 long-chain polyunsaturated fatty acid supplementation on urine
      protein excretion and kidney function: meta-analysis of clinical trials.
AB  - BACKGROUND: Chronic kidney disease is a major worldwide problem. Although
      epidemiologic and experimental studies suggest that n-3 long-chain
      polyunsaturated fatty acid (n-3 LCPUFA) supplementation may prevent or slow the
      progression of kidney disease, evidence from clinical trials is inconsistent.
      OBJECTIVE: The objective was to combine evidence from controlled clinical trials
      to assess the effect of n-3 LCPUFA supplementation on the change in urine protein
      excretion (UPE) and on glomerular filtration rate (GFR). DESIGN: We performed a
      meta-analysis of clinical trials that tested the effect of n-3 LCPUFA
      supplementation on UPE, a marker of kidney damage, and on GFR, a marker of kidney
      function. A random-effects model was used to pool SD effect size (Cohen's d)
      across studies. RESULTS: Seventeen trials with 626 participants were included in
      the meta-analysis. Most trials focused on patients with a single underlying
      diagnosis: IgA nephropathy (n = 5), diabetes (n = 7), or lupus nephritis (n = 1).
      The dose of n-3 LCPUFAs ranged from 0.7 to 5.1 g/d, and the median follow-up was
      9 mo. In the pooled analysis, there was a greater reduction in UPE in the n-3
      LCPUFA group than in the control group: Cohen's d for all trials was -0.19 (95%
      CI: -0.34, -0.04; P = 0.01). In a patient with 1 g UPE/d , this corresponds to a
      reduction of 190 mg/d. Effects on GFR were reported in 12 trials. The decline in
      GFR was slower in the n-3 LCPUFA group than in the control group, but this effect
      was not significant (0.11; 95% CI: -0.07, 0.29; P = 0.24). CONCLUSIONS: In our
      meta-analysis, use of n-3 LCPUFA supplements reduced UPE but not the decline in
      GFR. However, small numbers of participants in trials, different methods of
      assessing proteinuria and GFR, and inconsistent data reporting limit the strength
      of these conclusions. Large, high-quality trials with clinical outcomes are
      warranted.

PMID- 19403631
TI  - Studies of biomarker responses to intervention with riboflavin: a systematic
      review.
AB  - BACKGROUND: National survey data of erythrocyte glutathione reductase activation
      coefficient (EGRac) indicate that suboptimal riboflavin status may be a problem
      in all population age groups, but the cutoff for deficiency is controversial. In
      addition, the effectiveness of different biomarkers of riboflavin status has not
      been critically evaluated. OBJECTIVE: We aimed to assess the effectiveness of
      different biomarkers of riboflavin status through a systematic review of
      published riboflavin supplementation trials. DESIGN: We structured our search
      strategy on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases; formal inclusion
      and exclusion criteria; data extraction; validity assessment; and meta-analysis.
      RESULTS: Eighteen supplementation studies reporting up to 14 biomarkers were
      included. Sufficient data were available to show that EGRac (14 studies) and
      basal glutathione reductase activity (5 studies) were effective biomarkers of
      altered riboflavin intake (P < 0.00001), although substantial heterogeneity (I2 >
      66%) that could not be explained by the subgroup analysis was observed. Plasma
      total homocysteine was not an effective biomarker of riboflavin status in the
      general population, but some evidence identified its potential usefulness
      specifically in those homozygous for a common polymorphism in the MTHFR gene.
      CONCLUSIONS: The evidence suggests that EGRac is an effective biomarker of a
      change in riboflavin intake in populations with severe-to-normal baseline status.
      Studies of healthy populations that compare the response to low-dose
      supplementation among different age, sex, and MTHFR genotype groups are required
      to provide evidence for generating dietary riboflavin recommendations specific to
      different population subgroups. Further research into alternative biomarkers to
      EGRac is also required.

PMID- 19403632
TI  - Adolescent and adult soy food intake and breast cancer risk: results from the
      Shanghai Women's Health Study.
AB  - BACKGROUND: Soy food is a rich source of isoflavones--a class of phytoestrogens
      that has both antiestrogenic and anticarcinogenic properties. OBJECTIVE: The
      objective was to evaluate the association of adolescent and adult soy food intake
      with breast cancer risk in a cohort of 73,223 Chinese women who participated in
      the Shanghai Women's Health Study. DESIGN: A validated food-frequency
      questionnaire was used to assess usual dietary intake during adulthood and
      adolescence. After a mean follow-up of 7.4 y, 592 incident cases of breast cancer
      were identified for longitudinal analyses by using Cox regressions. RESULTS:
      Adult soy food consumption, measured either by soy protein or isoflavone intake,
      was inversely associated with the risk of premenopausal breast cancer, and the
      association was highly statistically significant (P for trend < 0.001). The
      multivariate-adjusted relative risks (RRs) for the upper intake quintile compared
      with the lowest quintile were 0.41 (95% CI: 0.25, 0.70) for soy protein intake
      and 0.44 (95% CI: 0.26, 0.73) for isoflavone intake. High intake of soy foods
      during adolescence was also associated with a reduced risk of premenopausal
      breast cancer (RR: 0.57; 95% CI: 0.34, 0.97). Women who consumed a high amount of
      soy foods consistently during adolescence and adulthood had a substantially
      reduced risk of breast cancer. No significant association with soy food
      consumption was found for postmenopausal breast cancer. CONCLUSION: This large,
      population-based, prospective cohort study provides strong evidence of a
      protective effect of soy food intake against premenopausal breast cancer.

PMID- 19403633
TI  - Assessing potential biomarkers of micronutrient status by using a systematic
      review methodology: methods.
AB  - BACKGROUND: To explore the relation between micronutrient status and health, it
      is important to understand which markers of micronutrient status can be relied on
      and under what circumstances. OBJECTIVE: The objective of this article was to
      develop a common systematic review methodology for use in the assessment of
      micronutrient status for selenium, iodine, copper, zinc, riboflavin, vitamin B
      12, vitamin D, and omega-3 (n-3) long-chain polyunsaturated fatty acids. DESIGN:
      We developed a methodology on the basis of defining studies that clearly altered
      micronutrient status and then pooled data on the effects of this intervention on
      each specific biomarker to assess objectively the response of various status
      markers to changes in intake. RESULTS: The generic methodology included defining,
      and systematically searching for, studies that resulted in a change in
      micronutrient status. Study inclusion, data extraction, and assessment of
      validity were conducted with a minimum of 10% independent duplication. For each
      study and each potential biomarker, the highest dose and longest duration
      intervention data were selected to assess the statistical significance of any
      change in intake on the status biomarker. The consistency of biomarker response
      was explored by subgrouping the studies according to baseline micronutrient
      status, sex, population group, supplementation type, dose, duration, and analytic
      method. CONCLUSION: This methodology allows systematic assessment of the
      usefulness of a number of biomarkers for a selection of micronutrients.

PMID- 19403634
TI  - Existing and potentially novel functional markers of vitamin D status: a
      systematic review.
AB  - BACKGROUND: Although serum 25-hydroxyvitamin D [25(OH)D] is the currently
      accepted vitamin D status marker of choice, use of other biomarkers or functional
      endpoints have been suggested. OBJECTIVE: The objective was to systematically
      review the effectiveness of 25(OH)D, parathyroid hormone (PTH), bone turnover
      markers, bone mineral density (BMD), and calcium absorption as biomarkers of
      vitamin D status. DESIGN: Methods included a structured search on Ovid MEDLINE,
      EMBASE (Ovid), and Cochrane CENTRAL; rigorous inclusion/exclusion criteria; data
      extraction; quality assessment; meta-analysis; and meta-regression. RESULTS:
      Thirty-six vitamin D supplementation randomized controlled trials (RCTs) and 4
      before-after studies were included. Vitamin D supplementation significantly
      raised circulating 25(OH)D in all but one RCT, but the response was highly
      heterogeneous [weighted mean difference (WMD): 34.1 nmol/L; 95% CI: 28.9, 39.2;
      32 RCTs; I2 = 97%). Vitamin D supplementation (without calcium) significantly
      lowered circulating PTH (WMD: -0.29 pmol/L; 95% CI: -0.56, -0.02; 11 RCTs; I2 =
      29%), but this was not apparent in the presence of calcium supplementation. There
      was a suggestion that whole-body or lumbar spine BMD may be a useful biomarker in
      older people but not in adolescents. Bone turnover markers were not useful
      biomarkers of vitamin D status, but 4 before-after studies suggested that
      intestinal calcium absorption may respond to vitamin D status. CONCLUSIONS: This
      systematic review confirmed that circulating 25(OH)D is a robust and reliable
      marker of vitamin D status. Further research is needed to clarify which
      population subgroups show responses of PTH, BMD, and/or calcium absorption in
      response to changes in vitamin D status.

PMID- 19403635
TI  - Milk decreases urinary excretion but not plasma pharmacokinetics of cocoa flavan
      3-ol metabolites in humans.
AB  - BACKGROUND: Cocoa drinks containing flavan-3-ols are associated with many health
      benefits, and conflicting evidence exists as to whether milk adversely affects
      the bioavailability of flavan-3-ols. OBJECTIVE: The objective was to determine
      the effect of milk on the bioavailability of cocoa flavan-3-ol metabolites.
      DESIGN: Nine human volunteers followed a low-flavonoid diet for 2 d before
      drinking 250 mL of a cocoa beverage, made with water or milk, that contained 45
      micromol (-)-epicatechin and (-)-catechin. Plasma and urine samples were
      collected for 24 h, and flavan-3-ol metabolites were analyzed by HPLC with
      photodiode array and mass spectrometric detection. RESULTS: Milk affected neither
      gastric emptying nor the transit time through the small intestine. Two flavan-3
      ol metabolites were detected in plasma and 4 in urine. Milk had only minor
      effects on the plasma pharmacokinetics of an (epi)catechin-O-sulfate and had no
      effect on an O-methyl-(epi)catechin-O-sulfate. However, milk significantly
      lowered the excretion of 4 urinary flavan-3-ol metabolites from 18.3% to 10.5% of
      the ingested dose (P = 0.016). Studies that showed protective effects of cocoa
      and those that showed no effect of milk on bioavailability used products that
      have a much higher flavan-3-ol content than does the commercial cocoa used in the
      present study. CONCLUSIONS: Most studies of the protective effects of cocoa have
      used drinks with a very high flavan-3-ol content. Whether similar protective
      effects are associated with the consumption of many commercial chocolate and
      cocoa products containing substantially lower amounts of flavan-3-ols, especially
      when absorption at lower doses is obstructed by milk, remains to be determined.

PMID- 19403638
TI  - Studies of biomarker responses to intervention with vitamin B-12: a systematic
      review of randomized controlled trials.
AB  - BACKGROUND: Mild vitamin B-12 deficiency is common among older adults, but
      evidence for setting dietary recommendations is limited because most studies have
      administered vitamin B-12 via nonoral routes or at doses several hundred times
      higher than current recommendations. Furthermore, different biomarkers of vitamin
      B-12 status have not been systematically reviewed. OBJECTIVE: The aim was to
      assess the effectiveness of biomarkers of vitamin B-12 status through a
      systematic review of published randomized controlled trials of oral vitamin B-12
      supplementation. DESIGN: Methods included a structured search strategy on Ovid
      MEDLINE, EMBASE (Ovid), and Cochrane databases; formal inclusion and exclusion
      criteria; data extraction; validity assessment; and meta-analysis. RESULTS: Eight
      randomized controlled trials were included, and all studies measured serum and
      plasma total vitamin B-12, 3 studies measured methylmalonic acid, and 6 studies
      measured total homocysteine response. All 3 biomarkers were found to be effective
      measures of altered vitamin B-12 intake in populations with low and borderline
      baseline vitamin B-12 status (P < 0.00001); however, in the case of total vitamin
      B-12, substantial heterogeneity that could not be fully explained by subgroup
      analysis was observed. Insufficient data were available to determine the
      effectiveness of plasma holotranscobalamin, which was measured in only one
      randomized controlled trial. CONCLUSIONS: The available evidence suggests that
      plasma and serum concentrations of total vitamin B-12, methylmalonic acid, and
      total homocysteine are all effective biomarkers of a change in vitamin B-12
      intake; however, because the available data were limited, it was not possible to
      examine fully the factors that could explain the substantial heterogeneity in
      total vitamin B-12. Future trials should include low-dose vitamin B-12 in adults
      across the entire age spectrum and measure the holotranscobalamin response to
      supplementation.

PMID- 19403637
TI  - Effects of selenomethionine supplementation on selenium status and thyroid
      hormone concentrations in healthy adults.
AB  - BACKGROUND: Selenium, a potential cancer prevention agent currently being tested
      against prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial
      (SELECT), plays an integral role in thyroid metabolism. The effects of long-term
      selenium supplementation on thyroid hormone concentrations are unknown.
      OBJECTIVE: The objective was to investigate the effects of long-term selenium
      supplementation on thyroid hormone concentrations. DESIGN: Twenty-eight healthy
      adults took 200 microg selenomethionine/d for 28 mo. The thyroid hormones
      triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) were measured in
      plasma for 4 mo before supplementation and quarterly during supplementation. The
      assay methods were changed midstudy; the results of the 2 methods were not
      comparable. Therefore, one analysis was conducted based on the results of the
      first method, and a second analysis was based on all of the data, adjusted for
      the change. Serial data collection permitted a test for trends rather than simply
      a difference between initial and final values. RESULTS: By 9 mo, mean (+/-SEM)
      plasma selenium concentrations had increased from 1.78 +/- 0.07 micromol/L at
      baseline to 2.85 +/- 0.11 micromol/L for men and from 1.64 +/- 0.04 to 3.32 +/-
      0.1.2 micromol/L for women. T3 concentrations in men increased 5% per year (P =
      0.01). T4 and TSH concentrations were unchanged. CONCLUSIONS: Selenium
      supplementation produced no clinically significant changes in thyroid hormone
      concentrations. A small but statistically significant increase in T3
      concentrations was noted in men, with no corresponding decreases in TSH. A subset
      of SELECT subjects might be monitored periodically for changes during long-term
      selenium supplementation.

PMID- 19403639
TI  - Prospective study of nut consumption, long-term weight change, and obesity risk
      in women.
AB  - BACKGROUND: Data concerning the long-term association between nut consumption and
      weight change in a free-living population are sparse. OBJECTIVE: The objective
      was to determine the relation between nut consumption and long-term weight
      change. DESIGN: The participants were 51,188 women in the Nurses' Health Study II
      aged 20-45 y, who had no cardiovascular disease, diabetes, or cancer. We
      prospectively evaluated the dietary intake of nuts and subsequent weight changes
      from 1991 to 1999. RESULTS: Women who reported eating nuts > or =2 times/wk had
      slightly less mean (+/- SE) weight gain (5.04 +/- 0.12 kg) than did women who
      rarely ate nuts (5.55 +/- 0.04 kg) (P for trend < 0.001). For the same
      comparison, when total nut consumption was subdivided into peanuts and tree nuts,
      the results were similar (ie, less weight gain in women eating either peanuts or
      tree nuts > or =2 times/wk). The results were similar in normal-weight,
      overweight, and obese participants. In multivariate analyses in which lifestyle
      and other dietary factors were controlled for, we found that greater nut
      consumption (> or =2 times/wk compared with never/almost never) was associated
      with a slightly lower risk of obesity (hazard ratio: 0.77; 95% CI: 0.57, 1.02; P
      for trend = 0.003). CONCLUSIONS: Higher nut consumption was not associated with
      greater body weight gain during 8 y of follow-up in healthy middle-aged women.
      Instead, it was associated with a slightly lower risk of weight gain and obesity.
      The results of this study suggest that incorporating nuts into diets does not
      lead to greater weight gain and may help weight control.

PMID- 19403640
TI  - Regular consumption of a complementary food fortified with ascorbic acid and
      ferrous fumarate or ferric pyrophosphate is as useful as ferrous sulfate in
      maintaining hemoglobin concentrations >105 g/L in young Bangladeshi children.
AB  - BACKGROUND: Non-water-soluble iron compounds have been reported to be less well
      absorbed than ferrous sulfate in young children, and concern has been raised
      about their usefulness as food fortificants. OBJECTIVE: The objective was to
      evaluate the usefulness of ferrous fumarate and ferric pyrophosphate, compared
      with ferrous sulfate, in maintaining hemoglobin concentrations >105 g/L in
      Bangladeshi children. DESIGN: Two hundred thirty-five children aged 7-24 mo
      (hemoglobin >105 g/L) were randomly assigned in a double-blind study to receive
      an infant cereal fortified with ferrous fumarate, ferric pyrophosphate, or
      ferrous sulfate. One serving of cereal (9.3 mg Fe; molar ratio of ascorbic acid
      to iron of 3:1) was consumed per day, 6 d/wk, for 9 mo. Blood samples were drawn
      at 4.5 and 9 mo. RESULTS: Raw data were reformatted, and a "time to event" was
      calculated that corresponded to reaching the following thresholds: hemoglobin
      <105 g/L, plasma ferritin <12 microg/L, or plasma C-reactive protein >10 mg/L at
      baseline, 4.5 mo, or 9 mo. Data were censored when children did not reach the
      threshold or were lost to follow-up. A Kaplan-Meier approach was used to compare
      the 3 groups. No statistically significant differences were observed for
      hemoglobin <105 g/L (P = 0.943), plasma ferritin <12 microg/L (P = 0.601), or
      plasma C-reactive protein >10 mg/L (P = 0.508). CONCLUSIONS: Contrary to earlier
      concerns, these results do not indicate differences in usefulness between water
      soluble and non-water-soluble iron compounds in maintaining hemoglobin
      concentrations and preventing iron deficiency. These data will be important in
      the development of food-fortification strategies to combat anemia and iron
      deficiency in highly vulnerable population groups.

PMID- 19403641
TI  - Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in
      healthy subjects with and without a family history of type 2 diabetes.
AB  - BACKGROUND: Both nutritional and genetic factors are involved in the pathogenesis
      of nonalcoholic fatty liver disease and insulin resistance. OBJECTIVE: The aim
      was to assess the effects of fructose, a potent stimulator of hepatic de novo
      lipogenesis, on intrahepatocellular lipids (IHCLs) and insulin sensitivity in
      healthy offspring of patients with type 2 diabetes (OffT2D)--a subgroup of
      individuals prone to metabolic disorders. DESIGN: Sixteen male OffT2D and 8
      control subjects were studied in a crossover design after either a 7-d isocaloric
      diet or a hypercaloric high-fructose diet (3.5 g x kg FFM(-1) x d(-1), +35%
      energy intake). Hepatic and whole-body insulin sensitivity were assessed with a 2
      step hyperinsulinemic euglycemic clamp (0.3 and 1.0 mU x kg(-1) x min(-1)),
      together with 6,6-[2H2]glucose. IHCLs and intramyocellular lipids (IMCLs) were
      measured by 1H-magnetic resonance spectroscopy. RESULTS: The OffT2D group had
      significantly (P < 0.05) higher IHCLs (+94%), total triacylglycerols (+35%), and
      lower whole-body insulin sensitivity (-27%) than did the control group. The high
      fructose diet significantly increased IHCLs (control: +76%; OffT2D: +79%), IMCLs
      (control: +47%; OffT2D: +24%), VLDL-triacylglycerols (control: +51%; OffT2D:
      +110%), and fasting hepatic glucose output (control: +4%; OffT2D: +5%).
      Furthermore, the effects of fructose on VLDL-triacylglycerols were higher in the
      OffT2D group (group x diet interaction: P < 0.05). CONCLUSIONS: A 7-d high
      fructose diet increased ectopic lipid deposition in liver and muscle and fasting
      VLDL-triacylglycerols and decreased hepatic insulin sensitivity. Fructose-induced
      alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the
      OffT2D group, which suggests that these individuals may be more prone to
      developing dyslipidemia when challenged by high fructose intakes. This trial was
      registered at clinicaltrials.gov as NCT00523562.

PMID- 19403642
TI  - Pressure activates epidermal growth factor receptor leading to the induction of
      iNOS via NFkappaB and STAT3 in human proximal tubule cells.
AB  - Ureteral obstruction leads to increased pressure and inducible nitric oxide
      synthase (iNOS) expression. This study examined the involvement of epidermal
      growth factor (EGF) receptor (EGFR), nuclear factor-kappaB (NFkappaB), and signal
      transducers and activators of transcription 3 (STAT3) in iNOS induction in human
      proximal tubule (HKC-8) cells in response to pressure or EGF. HKC-8 cells were
      subjected to 60 mmHg pressure or treated with EGF for 0-36 h. iNOS was more
      rapidly induced in response to EGF than pressure. The addition of EGFR, NFkappaB,
      and STAT3 inhibitors significantly suppressed pressure- or EGF-stimulated iNOS
      mRNA and protein expression. Analysis of the activated states of EGFR, NFkappaB
      p65, and STAT3 after exposure to both stimuli demonstrated phosphorylation within
      2.5 min. Anti-EGF antibody inhibited iNOS induction in pressurized HKC-8 cells,
      providing evidence that endogenous EGF mediates the response to pressure. In
      ureteral obstruction, when pressure is elevated, phosphorylated EGFR was detected
      in the apical surface of the renal tubules, validating the in vitro findings.
      These data indicate that EGFR, NFkappaB, and STAT3 are required for human iNOS
      gene induction in response to pressure or EGF, indicating a similar mechanism of
      activation.

PMID- 19403643
TI  - Kidney ischemia-reperfusion injury induces caspase-dependent pulmonary apoptosis.
AB  - Distant organ effects of acute kidney injury (AKI) are a leading cause of
      morbidity and mortality. While little is known about the underlying mechanisms,
      limited data suggest a role for inflammation and apoptosis. Utilizing a lung
      candidate gene discovery approach in a mouse model of ischemic AKI-induced lung
      dysfunction, we identified prominent lung activation of 66 apoptosis-related
      genes at 6 and/or 36 h following ischemia, of which 6 genes represent the tumor
      necrosis factor receptor (TNFR) superfamily, and another 23 genes are associated
      with the TNFR pathway. Given that pulmonary apoptosis is an important pathogenic
      mechanism of acute lung injury (ALI), we hypothesized that AKI leads to pulmonary
      proapoptotic pathways that facilitate lung injury and inflammation. Functional
      correlation with 1) terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling and 2) active caspase-3 (aC3) activity, immunoblotting, and
      immunohistochemistry (IHC) identified kidney IRI-induced pulmonary apoptosis at
      24 h, and colocalization studies with CD34 identified predominantly endothelial
      apoptosis. Mice were treated with the caspase inhibitor Z-VAD-FMK (0.25 mg ip) or
      vehicle 1 h before and 8 h after sham or kidney IRI, and bronchoalveolar lavage
      fluid protein was measured at 36 h as a surrogate for lung leak. Caspase
      inhibition reduced lung microvascular changes after kidney IRI. The pulmonary
      apoptosis seen in wild-type control mice during AKI was absent in TNFR(-/-) mice.
      Using an initial genomic approach to discovery followed by a mechanistic approach
      to disease targeting, we demonstrate that pulmonary endothelial apoptosis is a
      direct mediator of the distant organ dysfunction during experimental AKI.

PMID- 19403644
TI  - Organic anion transporter OAT1 is involved in renal handling of citrulline.
AB  - Because citrulline plasma concentration is elevated in kidney failure, citrulline
      could be a biomarker of renal insufficiency, although the mechanism regulating
      its disposition in the kidney has not been clarified. In rat kidney slices,
      citrulline uptake was apparently Na(+) dependent, saturable with K(m) 556 microM,
      and significantly inhibited by anionic (PAH) and cationic (TEA) compounds, but
      not by probenecid at 1 mM. Preincubation of kidney slices with glutarate
      increased citrulline uptake, while such an increase was not observed after
      preincubation of the slices in Na(+)-free buffer. This result suggested that a
      sodium-dependent dicarboxylate cotransporter is involved in citrulline uptake by
      rat kidney slices. In studies using transporter-overexpressing cells, human
      organic anion transporter 1 (OAT1) and rat Oat1 exhibited citrulline transport
      activity with K(m) values of 238 and 373 microM, respectively, while other OATs
      and organic cation transporters (OCTs) did not transport citrulline. Based on the
      relative activity factor method, the contribution of rat Oat1 to the overall
      uptake of citrulline in rat kidney slices was approximately 70%. Moreover, the
      interaction among citrulline, PAH, and probenecid uptakes via rat Oat1 suggested
      that there are multiple functional sites on Oat1 and that the citrulline site may
      be distinct from the PAH and probenecid site. Thus OAT1/Oat1 appears to be one of
      the major contributors to renal basolateral uptake of citrulline, and impaired
      activities of these transporters may contribute substantially to the increase in
      plasma citrulline in renal failure. Accordingly, citrulline may be useful for
      diagnosis of kidney function as is creatinine.

PMID- 19403636
TI  - Low-fat, increased fruit, vegetable, and grain dietary pattern, fractures, and
      bone mineral density: the Women's Health Initiative Dietary Modification Trial.
AB  - BACKGROUND: The effects of dietary changes on osteoporosis, low bone density, and
      frequent falls are unestablished. OBJECTIVE: We assessed the effect of the
      Women's Health Initiative Dietary Modification low-fat and increased fruit,
      vegetable, and grain intervention on incident hip, total, and site-specific
      fractures and self-reported falls, and, in a subset, on bone mineral density
      (BMD). DESIGN: Postmenopausal women (n = 48,835) aged 50-79 y (18.6% of minority
      race-ethnicity) were randomly assigned to receive the Dietary Modification
      intervention (40%, n = 19,541) (daily goal: < or =20% of energy as fat, > or =5
      servings of vegetables and fruit, and > or =6 servings of grains) or to a
      comparison group that received no dietary changes (60%; n = 29,294). RESULTS:
      After a mean 8.1 y of follow-up, 215 women in the intervention group and 285
      women in the comparison group (annualized rate: 0.14% and 0.12%, respectively)
      experienced a hip fracture (hazard ratio: 1.12; 95% CI: 0.94, 1.34; P = 0.21).
      The intervention group (n = 5423; annualized rate: 3.44%) had a lower rate of
      reporting > or =2 falls than did the comparison group (n = 8695; annualized rate:
      3.67%) (HR: 0.92; 95% CI: 0.89, 0.96; P < 0.01). There was a significant
      interaction according to hormone therapy use; those in the comparison group
      receiving hormone therapy had the lowest incidence of hip fracture. In a subset
      of 3951 women, hip BMD at years 3, 6, and 9 was 0.4-0.5% lower in the
      intervention group than in the comparison group (P = 0.003). CONCLUSIONS: A low
      fat and increased fruit, vegetable, and grain diet intervention modestly reduced
      the risk of multiple falls and slightly lowered hip BMD but did not change the
      risk of osteoporotic fractures. This trial was registered at clinicaltrials.gov
      as NCT00000611.

PMID- 19403645
TI  - A mathematical model of O2 transport in the rat outer medulla. II. Impact of
      outer medullary architecture.
AB  - we extended the region-based mathematical model of the urine-concentrating
      mechanism in the rat outer medulla (OM) developed by Layton and Layton (Am J
      Physiol Renal Physiol 289: F1346-F1366, 2005) to examine the impact of the
      complex structural organization of the OM on O(2) transport and distribution. In
      the present study, we investigated the sensitivity of predicted Po(2) profiles to
      several parameters that characterize the degree of OM regionalization, boundary
      conditions, structural dimensions, transmural transport properties, and relative
      positions and distributions of tubules and vessels. Our results suggest that the
      fraction of O(2) supplied to descending vasa recta (DVR) that reaches the inner
      medulla, i.e., a measure of the axial Po(2) gradient in the OM, is insensitive to
      parameter variations as a result of the sequestration of long DVR in the vascular
      bundles. In contrast, O(2) distribution among the regions surrounding the
      vascular core strongly depends on the radial positions of medullary thick
      ascending limbs (mTALs) relative to the vascular core, the degree of
      regionalization, and the distribution of short DVR along the corticomedullary
      axis. Moreover, if it is assumed that the mTAL active Na(+) transport rate
      decreases when mTAL Po(2) falls below a critical level, O(2) availability to
      mTALs has a significant impact on the concentrating capability of the model OM.
      The model also predicts that when the OM undergoes hypertrophy, its concentrating
      capability increases significantly only when anaerobic metabolism supports a
      substantial fraction of the mTAL active Na(+) transport and is otherwise
      critically reduced by low interstitial and mTAL luminal Po(2) in a hypertrophied
      OM.

PMID- 19403647
TI  - Antibodies to protein tyrosine phosphatase receptor type O (PTPro) increase
      glomerular albumin permeability (P(alb)).
AB  - Glomerular capillary filtration barrier characteristics are determined in part by
      the slit-pore junctions of glomerular podocytes. Protein tyrosine phosphatase
      receptor-O (PTPro) is a transmembrane protein expressed on the apical surface of
      podocyte foot processes. Tyrosine phosphorylation of podocyte proteins including
      nephrin may control the filtration barrier. To determine whether PTPro activity
      is required to maintain glomerular macromolecular permeability, albumin
      permeability (P(alb)) was studied after incubation of glomeruli from normal
      animals with a series of monoclonal (mAb) and polyclonal antibodies. Reagents
      included mAbs to rabbit and rat PTPro and polyclonal rabbit immune IgG to rat
      PTPro. mAb 4C3, specific to the amino acid core of PTPro, decreased its
      phosphatase activity and increased P(alb) of rabbit glomeruli in a time- and
      concentration-dependent manner. In contrast, mAb P8E7 did not diminish
      phosphatase activity and did not alter P(alb). Preincubation of 4C3 with PTPro
      extracellular domain fusion protein blocked glomerular binding and abolished
      permeability activity. In parallel experiments, P(alb) of rat glomeruli was
      increased by two mAbs (1B4 and 1D1) or by polyclonal anti-rat PTPro. We conclude
      that PTPro interaction with specific antibodies acutely increases P(alb). The
      identity of the normal ligand for PTPro and of its substrate, as well as the
      mechanism by which phosphatase activity of this receptor affects the filtration
      barrier, remain to be determined.

PMID- 19403648
TI  - PPARgamma agonists inhibit vasopressin-mediated anion transport in the MDCK-C7
      cell line.
AB  - PPARgamma agonists are synthetic ligands for the peroxisome proliferator
      activated receptor-gamma (PPARgamma). These agents have insulin-sensitizing
      properties but can cause fluid retention, thereby limiting their usefulness in
      patients at risk for cardiovascular disease. The side effect etiology is unknown,
      but the nature of presentation suggests modulation of renal salt and water
      homeostasis. In a well-characterized cell culture model of the principal cell
      type [Madin-Darby canine kidney (MDCK)-C7], PPARgamma agonists inhibit
      vasopressin-stimulated Cl(-) secretion with agonist dose-response relationships
      that mirror receptor transactivation profiles. Analyses of the components of the
      vasopressin-stimulated intracellular signaling pathway indicated no PPARgamma
      agonist-induced changes in basolateral membrane conductances, intracellular cAMP,
      protein kinase A, or total cellular adenine nucleotides. The PPARgamma agonist
      induced decrease in anion secretion is the result of decreased mRNA of the final
      effector in the pathway, the apically located cystic fibrosis transmembrane
      regulator (CFTR). These data showing that CFTR is a target for PPARgamma agonists
      may provide new insights into the physiology of PPARgamma agonist-induced fluid
      retention.

PMID- 19403646
TI  - A mathematical model of O2 transport in the rat outer medulla. I. Model
      formulation and baseline results.
AB  - The mammalian kidney is particularly vulnerable to hypoperfusion, because the
      O(2) supply to the renal medulla barely exceeds its O(2) requirements. In this
      study, we examined the impact of the complex structural organization of the rat
      outer medulla (OM) on O(2) distribution. We extended the region-based
      mathematical model of the rat OM developed by Layton and Layton (Am J Physiol
      Renal Physiol 289: F1346-F1366, 2005) to incorporate the transport of RBCs, Hb,
      and O(2). We considered basal cellular O(2) consumption and O(2) consumption for
      active transport of NaCl across medullary thick ascending limb epithelia. Our
      model predicts that the structural organization of the OM results in significant
      Po(2) gradients in the axial and radial directions. The segregation of descending
      vasa recta, the main supply of O(2), at the center and immediate periphery of the
      vascular bundles gives rise to large radial differences in Po(2) between regions,
      limits O(2) reabsorption from long descending vasa recta, and helps preserve O(2)
      delivery to the inner medulla. Under baseline conditions, significantly more O(2)
      is transferred radially between regions by capillary flow, i.e., advection, than
      by diffusion. In agreement with experimental observations, our results suggest
      that 79% of the O(2) supplied to the medulla is consumed in the OM and that
      medullary thick ascending limbs operate on the brink of hypoxia.

PMID- 19403650
TI  - Legalising active voluntary euthanasia through the courts: some lessons from
      Colombia.

PMID- 19403649
TI  - Mice lacking the ADP ribosyl cyclase CD38 exhibit attenuated renal
      vasoconstriction to angiotensin II, endothelin-1, and norepinephrine.
AB  - ADP ribosyl (ADPR) cyclases comprise a family of ectoenzymes recently shown to
      influence cytosolic Ca(2+) concentration in a variety of cell types. At least two
      ADPR cyclase family members have been identified in mammals: CD38 and CD157. We
      recently found reduced renal vascular reactivity to angiotensin II (ANG II),
      endothelin-1 (ET-1), and norepinephrine (NE) in the presence of the broad ADPR
      cyclase inhibitor nicotinamide. We hypothesized that CD38 mediates effects
      attributed to ADPR cyclase. We found expression of ADPR cyclases CD38 and CD157
      mRNA in spleen, thymus, skin, and preglomerular arterioles of wild-type (WT)
      animals. Mice lacking CD38 showed decreased CD157 expression in most tissues
      tested. No difference in systolic or mean arterial pressure was observed between
      strains in either conscious or anesthetized states, whereas heart rate was
      reduced 10-20% in CD38-/- animals (P < 0.05). During anesthesia, CD38-/- mice had
      reduced basal renal blood flow (RBF) and urine excretion (P < 0.05). RBF
      responses to intravenous injection of ANG II, ET-1, and NE were attenuated
      approximately 50% in CD38-/- vs. WT mice (P < 0.01 for all). The systemic pressor
      response to ANG II was decreased in the absence of CD38 (P < 0.01), whereas that
      to NE was normal (P > 0.05); ET-1 was administered at a nonpressor dose.
      Nicotinamide effectively inhibited ANG II-induced renal vasoconstriction in WT
      mice (P < 0.001), but had no effect on renal responses to ANG II in CD38-/- mice
      (P > 0.5). Overall, our observations indicate the presence of two ADPR cyclase
      family members in renal preglomerular resistance arterioles and the importance of
      CD38 participation in acute vascular responses to all three vasoconstrictors in
      the renal microcirculation.

PMID- 19403653
TI  - Rapid decline in the efficiency of HIV drug resistance genotyping from dried
      blood spots (DBS) and dried plasma spots (DPS) stored at 37 degrees C and high
      humidity.
AB  - OBJECTIVES: Dried blood spots (DBS) and dried plasma spots (DPS) are considered
      convenient alternatives to serum and plasma for HIV drug resistance testing in
      resource-limited settings. We sought to investigate how extreme conditions could
      affect the short-term ability to amplify and genotype HIV from DBS. METHODS: A
      panel of six matched DPS/DBS was generated using blood collected from HIV
      infected donors. Replicate cards were prepared in 903 filter paper using 50
      microL of blood and stored at either -20 degrees C or at 37 degrees C/100%
      humidity. Nucleic acids were extracted at baseline and after 1, 2, 8 and 16 weeks
      of storage and were amplified and sequenced using an in-house RT-nested PCR
      method or the ViroSeq assay. RESULTS: HIV-1 pol was successfully amplified in all
      DBS/DPS at baseline and in those stored for up to 16 weeks at -20 degrees C by
      the in-house assay. In contrast, amplification was rapidly lost during storage at
      37 degrees C/100% humidity with only 6/6 and 4/6 DBS specimens amplifiable by the
      in-house assay at weeks 1 and 2, respectively. Similarly, only two DPS stored at
      37 degrees C/100% humidity were amplified by the in-house assay at week 1.
      CONCLUSIONS: We show that resistance testing from DBS and DPS is severely
      compromised after 2 and 1 weeks of storage at 37 degrees C/100% humidity with
      desiccant, respectively. These findings underscore the importance of temperature
      and humidity for the efficient genotyping of HIV-1 from DBS and DPS, and
      reiterate the need to rapidly transport specimens from collection sites to
      locations that have appropriate storage conditions such as -20 degrees C.

PMID- 19403652
TI  - A randomized trial of two-drug versus three-drug tenofovir-containing maintenance
      regimens in virologically controlled HIV-1 patients.
AB  - OBJECTIVES: To assess simplified maintenance regimens containing dual
      antiretroviral drugs in patients with controlled human immunodeficiency virus
      type 1 infection. METHODS: A non-inferiority, randomized, multicentre, open-label
      trial was performed in 24 AIDS clinical centres in France randomizing 143
      patients [treated for >or=6 months, plasma viral load (pVL) <50 copies/mL, no
      prior history of treatment failure] to receive a two-drug regimen [tenofovir
      disoproxil fumarate (tenofovir DF) and efavirenz] or to maintain a three-drug
      treatment (tenofovir DF, lamivudine and efavirenz). The main outcome measure was
      the success rate (percentage of patients with pVL <50 copies/mL without treatment
      modifications) at week 48. RESULTS: Success rates for the intention-to-treat
      analysis were 97.2% (70/72) versus 81.7% (58/71) in the three-drug versus two
      drug maintenance regimen groups, respectively [difference, 15.5%; upper limit of
      one-sided 95% confidence interval (CI), 23.7%], and 100% (70/70) versus 90%
      (54/60) for the per protocol analysis, respectively (difference, 10%; upper limit
      of one-sided 95% CI, 16.4%), with a non-inferiority margin set at 14%. Three
      patients from the two-drug group experienced virological failure with selection
      of efavirenz-associated mutations. Overall, CD4 counts were significantly
      increased from baseline (median, +24 cells/mm(3); P = 0.007). Four patients
      discontinued study treatment due to adverse events in the two-drug group and none
      in the three-drug group. No significant changes in creatinine clearance or
      phosphataemia were reported. Overall, levels of triglycerides, total and high
      density lipoprotein cholesterol were improved; low-density lipoprotein
      cholesterol was improved only in the three-drug group. CONCLUSIONS: The non
      inferiority of the two-drug versus the three-drug regimen was not demonstrated.
      Lipid parameters improved after switching from twice-daily highly active
      antiretroviral therapy (HAART) to once-daily tenofovir-based HAART.

PMID- 19403654
TI  - C-terminal provasopressin (copeptin) in patients with community-acquired
      pneumonia--influence of antibiotic pre-treatment: results from the German
      competence network CAPNETZ.
AB  - BACKGROUND: Recently, C-terminal provasopressin (copeptin) turned out to be
      predictive for mortality in community-acquired pneumonia (CAP). The aim of this
      study was to evaluate the influence of antibiotic pre-treatment on copeptin
      levels in CAP. METHODS: We enrolled 370 hospitalized patients (66 +/- 17 years;
      42% females) with proven CAP. Venous blood samples were collected at the time of
      inclusion into the study and as soon as possible after the diagnosis of CAP.
      Copeptin (B.R.A.H.M.S. AG, Henningsdorf, Germany) levels were determined in
      venous blood on admission. RESULTS: Eighty-five patients had antibiotic pre
      treatment and 285 patients did not. Copeptin levels increased with increasing
      severity of CAP in patients without antibiotic pre-treatment but not in patients
      with antibiotic pre-treatment. Patients with prior antibiotic treatment showed
      significantly lower levels of copeptin [median (interquartile range): 12.8 (5.3
      22.6) versus 20.8 (11.1-37.8) pmol/L, P < 0.0001] and procalcitonin [0.15 (0.07
      0.38) versus 0.27 (0.10-1.52) ng/mL, P = 0.0003], but not C-reactive protein [113
      (46-229) versus 122 (49-231) mg/mL, not significant] and leucocytes [12.2 x 10(3)
      (8.1 x 10(3)-15.4 x 10(3)) versus 12.5 x 10(3) (9.4 x 10(3)-16.3 x 10(3))
      cells/mm(3), not significant] compared with those without antibiotic pre
      treatment. CONCLUSIONS: Copeptin serum levels are higher in patients without
      antibiotic pre-treatment compared with those with antibiotic pre-treatment.
      Copeptin serum levels increase with an increasing severity of CAP in patients
      without, but not in patients with, antibiotic pre-treatment. Thus, antibiotic pre
      treatment has to be taken into account for the correct interpretation of copeptin
      levels in CAP.

PMID- 19403656
TI  - Multiple roles for Sox2 in the developing and adult mouse trachea.
AB  - The esophagus, trachea and lung develop from the embryonic foregut, yet acquire
      and maintain distinct tissue phenotypes. Previously, we demonstrated that the
      transcription factor Sox2 is necessary for foregut morphogenesis and esophagus
      development. We show that Sox2 is also required for the normal development of the
      trachea and lung. In both the embryo and adult, Sox2 is exclusively expressed in
      the epithelium of the trachea and airways. We use an Nkx2.5-Cre transgene and a
      Sox2 floxed allele to conditionally delete Sox2 in the ventral epithelial domain
      of the early anterior foregut, which gives rise to the future trachea and lung
      buds. All conditional mutants die of respiratory distress at birth, probably due
      to abnormal differentiation of the laryngeal and tracheal cartilage as a result
      of defective epithelial-mesenchymal interaction. About 60% of the mutants have a
      short trachea, suggesting that the primary budding site of the lung shifts
      anteriorly. In the tracheal epithelium of all conditional mutants there are
      significantly more mucus-producing cells compared with wild type, and fewer basal
      stem cells, ciliated and Clara cells. Differentiation of the epithelium lining
      the conducting airways in the lung is abnormal, suggesting that Sox2 also plays a
      role in the differentiation of embryonic airway progenitors into specific
      lineages. Conditional deletion of Sox2 was then used to test its role in adult
      epithelium maintenance. We found that epithelial cells, including basal stem
      cells, lacking Sox2 show a reduced capacity to proliferate in culture and to
      repair after injury in vivo. Taken together, these results define multiple roles
      for Sox2 in the developing and adult trachea.

PMID- 19403657
TI  - Brca1 is required for embryonic development of the mouse cerebral cortex to
      normal size by preventing apoptosis of early neural progenitors.
AB  - The extent of apoptosis of neural progenitors is known to influence the size of
      the cerebral cortex. Mouse embryos lacking Brca1, the ortholog of the human
      breast cancer susceptibility gene BRCA1, show apoptosis in the neural tube, but
      the consequences of this for brain development have not been studied. Here we
      investigated the role of Brca1 during mouse embryonic cortical development by
      deleting floxed Brca1 using Emx1-Cre, which leads to conditional gene ablation
      specifically in the dorsal telencephalon after embryonic day (E) 9.5. The
      postnatal Brca1-ablated cerebral cortex was substantially reduced in size with
      regard to both cortical thickness and surface area. Remarkably, although the
      thickness of the cortical layers (except for the upper-most layer) was decreased,
      cortical layering as such was essentially unperturbed. High levels of apoptosis
      were found at E11.5 and E13.5, but dropped to near-control levels by E16.5. The
      apoptosis at the early stage of neurogenesis occurred in both BrdU pulse-labeled
      neural progenitors and the neurons derived therefrom. No changes were observed in
      the mitotic index of apical (neuroepithelial, radial glial) progenitors and basal
      (intermediate) progenitors, indicating that Brca1 ablation did not affect cell
      cycle progression. Brca1 ablation did, however, result in the nuclear
      translocation of p53 in neural progenitors, suggesting that their apoptosis
      involved activation of the p53 pathway. Our results show that Brca1 is required
      for the cerebral cortex to develop to normal size by preventing the apoptosis of
      early cortical progenitors and their immediate progeny.

PMID- 19403658
TI  - Neuropilin receptors guide distinct phases of sensory and motor neuronal
      segmentation.
AB  - The segmented trunk peripheral nervous system is generated by ventrally migrating
      neural crest cells that exclusively invade the anterior sclerotome and
      differentiate into metameric dorsal root and sympathetic ganglia. Meanwhile,
      ventral spinal motor axons also project through the somites in a segmental
      fashion. How peripheral nervous system segmentation is generated is unknown. We
      previously showed that neuropilin 2 (Nrp2)/semaphorin 3F (Sema3F) signaling is
      required for segmental neural crest migration, but not for metameric dorsal root
      gangliogenesis. We now expand these results to show that Nrp2 patterns initial
      motor axon outgrowth as well. Later, Nrp1/Sema3A signaling is essential for
      segmental dorsal root gangliogenesis and motor axonal fasciculation into ventral
      roots. Strikingly, Nrp/Sema signaling is not required for sympathetic ganglia
      segmentation. These data show that Nrp2 and Nrp1 work together to produce
      segmentation of sensory and motor nerves, and that dorsal peripheral nervous
      system metamerism is generated in a stepwise, Nrp-dependent process.

PMID- 19403659
TI  - The tetraspanin Tm4sf3 is localized to the ventral pancreas and regulates fusion
      of the dorsal and ventral pancreatic buds.
AB  - During embryogenesis, the pancreas develops from separate dorsal and ventral
      buds, which fuse to form the mature pancreas. Little is known about the
      functional differences between these two buds or the relative contribution of
      cells derived from each region to the pancreas after fusion. To follow the fate
      of dorsal or ventral bud derived cells in the pancreas after fusion, we produced
      chimeric Elas-GFP transgenic/wild-type embryos in which either dorsal or ventral
      pancreatic bud cells expressed GFP. We found that ventral pancreatic cells
      migrate extensively into the dorsal pancreas after fusion, whereas the converse
      does not occur. Moreover, we found that annular pancreatic tissue is composed
      exclusively of ventral pancreas-derived cells. To identify ventral pancreas
      specific genes that may play a role in pancreatic bud fusion, we isolated
      individual dorsal and ventral pancreatic buds, prior to fusion, from NF38/39
      Xenopus laevis tadpoles and compared their gene expression profiles (NF refers to
      the specific stage of Xenopus development). As a result of this screen, we have
      identified several new ventral pancreas-specific genes, all of which are
      expressed in the same location within the ventral pancreas at the junction where
      the two ventral pancreatic buds fuse. Morpholino-mediated knockdown of one of
      these ventral-specific genes, transmembrane 4 superfamily member 3 (tm4sf3),
      inhibited dorsal-ventral pancreatic bud fusion, as well as acinar cell
      differentiation. Conversely, overexpression of tm4sf3 promoted development of
      annular pancreas. Our results are the first to define molecular and behavioral
      differences between the dorsal and ventral pancreas, and suggest an unexpected
      role for the ventral pancreas in pancreatic bud fusion.

PMID- 19403660
TI  - FOXD3 regulates the lineage switch between neural crest-derived glial cells and
      pigment cells by repressing MITF through a non-canonical mechanism.
AB  - The first neural crest cells to emigrate from the neural tube are specified as
      neurons and glial cells and are subsequently followed by melanocytes of the skin.
      We wished to understand how this fate switch is controlled. The transcriptional
      repressor FOXD3 is expressed exclusively in the neural/glial precursors and MITF
      is expressed only in melanoblasts. Moreover, FOXD3 represses melanogenesis. Here
      we show that avian MITF expression begins very early during melanoblast migration
      and that loss of MITF in melanoblasts causes them to transdifferentiate to a
      glial phenotype. Ectopic expression of FOXD3 represses MITF in cultured neural
      crest cells and in B16-F10 melanoma cells. We also show that FOXD3 does not bind
      directly to the MITF promoter, but instead interacts with the transcriptional
      activator PAX3 to prevent the binding of PAX3 to the MITF promoter.
      Overexpression of PAX3 is sufficient to rescue MITF expression from FOXD3
      mediated repression. We conclude that FOXD3 controls the lineage choice between
      neural/glial and pigment cells by repressing MITF during the early phase of
      neural crest migration.

PMID- 19403661
TI  - Mechanical control of global cell behaviour during dorsal closure in Drosophila.
AB  - Halfway through embryonic development, the epidermis of Drosophila exhibits a gap
      at the dorsal side covered by an extraembryonic epithelium, the amnioserosa (AS).
      Dorsal closure (DC) is the process whereby interactions between the two epithelia
      establish epidermal continuity. Although genetic and biomechanical analysis have
      identified the AS as a force-generating tissue, we do not know how individual
      cell behaviours are transformed into tissue movements. To approach this question
      we have applied a novel image-analysis method to measure strain rates in local
      domains of cells and performed a kinematic analysis of DC. Our study reveals
      spatial and temporal differences in the rate of apical constriction of AS cells.
      We find a slow phase of DC, during which apical contraction of cells at the
      posterior end predominates, and a subsequent fast phase, during which all the
      cells engage in the contraction, which correlates with the zippering process.
      There is a radial gradient of AS apical contraction, with marginal cells
      contracting earlier than more centrally located cells. We have applied this
      analysis to the study of mutant situations and associated a particular genotype
      with quantitative and reproducible changes in the rate of cell contraction and
      hence in the overall rate of the process. Our mutant analysis reveals the
      contribution of mechanical elements to the rate and pattern of DC.

PMID- 19403662
TI  - Extracellular matrix modifications at fertilization: regulation of dityrosine
      crosslinking by transamidation.
AB  - Fertilization is accompanied by the construction of an extracellular matrix that
      protects the new zygote. In sea urchins, this structure is built from
      glycoproteins residing at the egg surface and in secretory vesicles at the egg
      cortex. Four enzymatic activities are required for the transformation of these
      proteins into the mechanically and chemically resilient fertilization envelope:
      proteolysis, transamidation, NADPH-dependent oxidation and peroxidation. Here, we
      identify the Strongylocentrotus purpuratus enzymes responsible for the formation
      of epsilon(gamma-glutamyl)lysine crosslinks (transamidation). We find that these
      two transglutaminases are activated by local acidification and act on specific
      substrates within the fertilization envelope (including ovoperoxidase, rendezvin
      and SFE9). Surprisingly, these enzymes also regulate dityrosine crosslinking both
      by direct conjugation of ovoperoxidase and by modulating hydrogen peroxide
      production. Together, these results emphasize how transglutaminases can
      coordinate the activities of other enzymes during extracellular matrix
      transmogrifications.

PMID- 19403664
TI  - Multiple integrated copies and high-level production of the human retrovirus XMRV
      (xenotropic murine leukemia virus-related virus) from 22Rv1 prostate carcinoma
      cells.
AB  - The human retrovirus XMRV (xenotropic murine leukemia virus-related virus) is
      associated with prostate cancer, most frequently in humans with a defect in the
      antiviral defense protein RNase L, suggesting a role for XMRV in prostate
      carcinogenesis. However, XMRV has not been found in prostate carcinoma cells.
      Here we show that 22Rv1 prostate carcinoma cells produce high-titer virus that is
      nearly identical in properties and sequence to XMRV isolated by others and
      consist primarily of a single clone of cells with at least 10 integrated copies
      of XMRV, warranting further study of a possible role for XMRV integration in
      carcinogenesis.

PMID- 19403665
TI  - Murine norovirus infection has no significant effect on adaptive immunity to
      vaccinia virus or influenza A virus.
AB  - Murine norovirus (MNV) is endemic in many research mouse colonies. Although MNV
      infections are typically asymptomatic in immunocompetent mice, the effects of MNV
      infection on subsequent experimental viral infections are poorly documented.
      Here, we infected C57BL/6 mice with MNV and then with either vaccinia virus or
      influenza A virus. MNV infection had no effect on CD8(+) T-cell or antibody
      responses to secondary viruses or to secondary virus-induced morbidity or
      mortality. While our findings suggest that MNV has little influence on host
      immunity in immunocompetent mice, we would urge caution regarding the potential
      effects of MNV on immune responses to viruses and other pathogens, which must be
      determined on a system-by-system basis.

PMID- 19403663
TI  - Adenovirus vectors expressing hantavirus proteins protect hamsters against lethal
      challenge with andes virus.
AB  - Hantaviruses infect humans following aerosolization from rodent feces and urine,
      producing hemorrhagic fever with renal syndrome and hantavirus pulmonary
      syndrome. Due to the high rates of mortality and lack of therapies, vaccines are
      urgently needed. Nonreplicating adenovirus (Ad) vectors that express Andes
      hantavirus (ANDV) nucleocapsid protein (AdN) or glycoproteins (AdG(N) and AdG(C))
      were constructed. Ad vectors were tested for their ability to protect Syrian
      hamsters from a lethal ANDV infection that mimics the pulmonary disease seen in
      humans. When administered once, all three Ad vectors, individually or in
      combination, elicited a robust immune response that protected hamsters. No
      vaccinated animal died, and there were no obvious clinical signs of disease.
      Further, hantavirus RNA was not detected by sensitive reverse transcription-PCR
      in tissues and blood of hamsters immunized with both AdG(N) and AdG(C). Cellular
      immunity appeared to be important for protection because the AdN vector
      completely protected animals. All three Ad vectors produced strong cytotoxic T
      lymphocyte responses directed to hantavirus proteins in mice. Moreover, hamsters
      vaccinated with AdN, AdG(N), or AdG(C) produced no detectable neutralizing
      antibodies yet were protected. These Ad vectors represent the first vaccines that
      prevent lethal hantavirus disease and, in some instances (AdG(N) and AdG(C)),
      provide sterile immunity. These observations set the stage for a more detailed
      characterization of the types of immunity required to protect humans from
      hantavirus infections.

PMID- 19403666
TI  - Downregulation of RUNX1 by RUNX3 requires the RUNX3 VWRPY sequence and is
      essential for Epstein-Barr virus-driven B-cell proliferation.
AB  - Cross-regulation of RUNX1 expression by RUNX3 plays a critical role in regulating
      proliferation of human B cells infected with Epstein-Barr virus (EBV). When EBV
      infection induces RUNX3, the consequent reduction in RUNX1 levels is required for
      the ensuing cell proliferation because forced expression of RUNX1 in an EBV
      lymphoblastoid cell line prevented cell proliferation. The TEL-RUNX1 fusion gene
      from acute B-lymphocytic leukemia retains almost all of the RUNX1 sequence but
      does not prevent B-cell proliferation in the same assay. B-cell maturation
      antigen (BCMA) was found to be induced by conditionally expressed RUNX3 in a
      lymphoma cell line. Chromatin immunoprecipitation assays confirmed that RUNX3
      binds to the RUNX1 promoter in a lymphoblastoid cell line and a Burkitt's
      lymphoma cell line. The TLE binding VWRPY sequence from the C terminus of RUNX3
      was found to be required for repression of the RUNX1 P1 promoter in a B-lymphoma
      cell line. The mechanism of repression in B-cell lines most likely involves
      recruitment of corepressor TLE3 or TLE4 to the RUNX1 promoter. The results
      demonstrate the importance of RUNX3-mediated repression of RUNX1 for EBV-driven B
      cell proliferation and identify functional differences between human RUNX family
      proteins.

PMID- 19403667
TI  - X-box binding protein 1 contributes to induction of the Kaposi's sarcoma
      associated herpesvirus lytic cycle under hypoxic conditions.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), like other herpesviruses, has two
      stages to its life cycle: latency and lytic replication. KSHV is required for
      development of Kaposi's sarcoma, a tumor of endothelial origin, and is associated
      with the B-cell tumor primary effusion lymphoma (PEL) and the plasmablastic
      variant of multicentric Castleman's disease, all of which are characterized by
      predominantly latent KSHV infection. Recently, we and others have shown that the
      activated form of transcription factor X-box binding protein 1 (XBP-1) is a
      physiological trigger of KSHV lytic reactivation in PEL. Here, we show that XBP
      1s transactivates the ORF50/RTA promoter though an ACGT core containing the XBP-1
      response element, an element previously identified as a weakly active hypoxia
      response element (HRE). Hypoxia induces the KSHV lytic cycle, and active HREs
      that respond to hypoxia-inducible factor 1alpha are present in the ORF50/RTA
      promoter. Hypoxia also induces active XBP-1s, and here, we show that both
      transcription factors contribute to the induction of RTA expression, leading to
      the production of infectious KSHV under hypoxic conditions.

PMID- 19403668
TI  - Onset of human cytomegalovirus replication in fibroblasts requires the presence
      of an intact vimentin cytoskeleton.
AB  - Like all viruses, herpesviruses extensively interact with the host cytoskeleton
      during entry. While microtubules and microfilaments appear to facilitate viral
      capsid transport toward the nucleus, evidence for a role of intermediate
      filaments in herpesvirus entry is lacking. Here, we examined the function of
      vimentin intermediate filaments in fibroblasts during the initial phase of
      infection of two genotypically distinct strains of human cytomegalovirus (CMV),
      one with narrow (AD169) and one with broad (TB40/E) cell tropism. Chemical
      disruption of the vimentin network with acrylamide, intermediate filament
      bundling in cells from a patient with giant axonal neuropathy, and absence of
      vimentin in fibroblasts from vimentin(-/-) mice severely reduced entry of either
      strain. In vimentin null cells, viral particles remained in the cytoplasm longer
      than in vimentin(+/+) cells. TB40/E infection was consistently slower than that
      of AD169 and was more negatively affected by the disruption or absence of
      vimentin. These findings demonstrate that an intact vimentin network is required
      for CMV infection onset, that intermediate filaments may function during viral
      entry to facilitate capsid trafficking and/or docking to the nuclear envelope,
      and that maintenance of a broader cell tropism is associated with a higher degree
      of dependence on the vimentin cytoskeleton.

PMID- 19403669
TI  - Rhinovirus 3C protease can localize in the nucleus and alter active and passive
      nucleocytoplasmic transport.
AB  - The degradation of nuclear pore components and disruption of nucleocytoplasmic
      trafficking during rhinovirus infection have been attributed to viral 2A
      protease. Here we show for the first time that rhinovirus 3C protease may also
      have a role. Specifically, we show that 3C and its precursor, 3CD, can target
      green fluorescent protein to the nucleus of living cells, leading to degradation
      of nuclear pore components, and that incubation with recombinant 3C disrupts
      active and passive nucleocytoplasmic transport in a semi-intact cell nuclear
      transport system dependent on 3C protease activity. 3C may thus contribute to
      host cell shutoff in infected cells by localizing in the nucleus and facilitating
      nuclear pore breakdown.

PMID- 19403670
TI  - A shared interface mediates paramyxovirus interference with antiviral RNA
      helicases MDA5 and LGP2.
AB  - Diverse members of the Paramyxovirus family of negative-strand RNA viruses
      effectively suppress host innate immune responses through the actions of their V
      proteins. The V protein mediates interference with the interferon regulatory RNA
      helicase MDA5 to avoid cellular antiviral responses. Analysis of the interaction
      interface revealed the MDA5 helicase C domain as necessary and sufficient for
      association with V proteins from human parainfluenza virus type 2, parainfluenza
      virus type 5, measles virus, mumps virus, Hendra virus, and Nipah virus. The
      identified approximately 130-residue region is highly homologous between MDA5 and
      the related antiviral helicase LGP2, but not RIG-I. Results indicate that the
      paramyxovirus V proteins can also associate with LGP2. The V protein interaction
      was found to disrupt ATP hydrolysis mediated by both MDA5 and LGP2. These
      findings provide a potential mechanistic basis for V protein-mediated helicase
      interference and identify LGP2 as a second cellular RNA helicase targeted by
      paramyxovirus V proteins.

PMID- 19403671
TI  - Human immunodeficiency virus type 1 Gag p24 alters the composition of
      immunoproteasomes and affects antigen presentation.
AB  - Proteasomes are the major source of proteases responsible for the generation of
      peptides bound to major histocompatibility complex class I molecules. Antigens,
      adjuvants, and cytokines can modulate the composition and enzymatic activity of
      proteasomes and thus alter the epitopes generated. In the present study, we
      examined the effect of human immunodeficiency virus type 1 (HIV-1) p24 on
      proteasomes from a dendritic cell line (JAWS II), from a macrophage cell line
      (C2.3), and from murine primary bone marrow-derived macrophages and dendritic
      cells. HIV-1 p24 downregulated PA28beta and the beta2i subunit of the
      immunoproteasome complex in JAWS II cells but did not decrease the
      immunoproteasome subunits in macrophages, whereas in primary dendritic cells,
      PA28alpha, beta2i, and beta5i were downregulated. Exposure of JAWS II cells and
      primary dendritic cells to HIV-1 p24 for 90 min significantly decreased the
      presentation of ovalbumin to a SIINFEKL-specific CD8(+) T-cell hybridoma. The
      decrease in antigen presentation and the downmodulation of the immunoproteasome
      subunits in JAWS II cells and primary dendritic cells could be overcome by
      pretreating the cells with gamma interferon for 6 h or by exposing the cells to
      HIV-1 p24 encapsulated in liposomes containing lipid A. These results suggest
      that early antigen processing kinetics could influence the immunogenicity of
      CD8(+) T-cell epitopes generated.

PMID- 19403672
TI  - Biological effect of Muller's Ratchet: distant capsid site can affect
      picornavirus protein processing.
AB  - Repeated bottleneck passages of RNA viruses result in accumulation of mutations
      and fitness decrease. Here, we show that clones of foot-and-mouth disease virus
      (FMDV) subjected to bottleneck passages, in the form of plaque-to-plaque
      transfers in BHK-21 cells, increased the thermosensitivity of the viral clones.
      By constructing infectious FMDV clones, we have identified the amino acid
      substitution M54I in capsid protein VP1 as one of the lesions associated with
      thermosensitivity. M54I affects processing of precursor P1, as evidenced by
      decreased production of VP1 and accumulation of VP1 precursor proteins. The
      defect is enhanced at high temperatures. Residue M54 of VP1 is exposed on the
      virion surface, and it is close to the B-C loop where an antigenic site of FMDV
      is located. M54 is not in direct contact with the VP1-VP3 cleavage site,
      according to the three-dimensional structure of FMDV particles. Models to account
      for the effect of M54 in processing of the FMDV polyprotein are proposed. In
      addition to revealing a distance effect in polyprotein processing, these results
      underline the importance of pursuing at the biochemical level the biological
      defects that arise when viruses are subjected to multiple bottleneck events.

PMID- 19403673
TI  - Divergent Bro1 domains share the capacity to bind human immunodeficiency virus
      type 1 nucleocapsid and to enhance virus-like particle production.
AB  - To promote the release of infectious virions, human immunodeficiency virus type 1
      (HIV-1) exploits the endosomal sorting complex required for transport (ESCRT)
      pathway by engaging Tsg101 and ALIX through late assembly (L) domains in p6 Gag.
      An LYPx(n)L motif in p6 serves as docking site for the central V domain of ALIX
      and is required for its ability to stimulate HIV-1 budding. Additionally, the
      nucleocapsid (NC) domain of Gag binds to the N-terminal Bro1 domain of ALIX,
      which connects ALIX to the membrane-deforming ESCRT-III complex via its CHMP4
      subunits. Since the isolated Bro1 domain of ALIX is sufficient to markedly
      stimulate virus-like particle (VLP) production in a minimal Gag rescue assay, we
      examined whether the Bro1 domains of other human proteins possess a similar
      activity. We now show that the Bro1 domain-only protein Brox and the isolated
      Bro1 domains of HD-PTP and rhophilin all bind to HIV-1 NC. Furthermore, all
      shared the capacity to stimulate VLP production by a minimal HIV-1 Gag molecule,
      and Brox in particular was as potent as the Bro1 domain of ALIX in this assay.
      Unexpectedly, Brox retained significant activity even if its CHMP4 binding site
      was disrupted. Thus, the ability to assist in VLP production may be an intrinsic
      property of the boomerang-shaped Bro1 domain.

PMID- 19403675
TI  - Primary high-dose murine norovirus 1 infection fails to protect from secondary
      challenge with homologous virus.
AB  - Human noroviruses in the Caliciviridae family are the major cause of nonbacterial
      epidemic gastroenteritis worldwide. Primary human norovirus infection does not
      elicit lasting protective immunity, a fact that could greatly affect the efficacy
      of vaccination strategies. Little is known regarding the pathogenesis of human
      noroviruses or the immune responses that control them because there has
      previously been no small-animal model or cell culture system of infection. Using
      the only available small-animal model of norovirus infection, we found that
      primary high-dose murine norovirus 1 (MNV-1) infection fails to afford protection
      against a rechallenge with a homologous virus. Thus, MNV-1 represents a valuable
      model with which to dissect the pathophysiological basis for the lack of lasting
      protection against human norovirus infection. Interestingly, the magnitude of
      protection afforded by a primary MNV-1 infection inversely correlates with the
      inoculum dose. Future studies will elucidate the mechanisms by which noroviruses
      avoid the induction of protective immunity and the role played by the inoculum
      dose in this process, ultimately translating this knowledge into successful
      vaccination approaches.

PMID- 19403674
TI  - Nuclear-cytoplasmic shuttling is not required for the Epstein-Barr virus EBNA-LP
      transcriptional coactivation function.
AB  - Epstein-Barr virus (EBV) EBNA-LP is a transcriptional coactivator of EBNA2 that
      works though interaction with the promyelocytic leukemia nuclear-body-associated
      protein Sp100A. EBNA-LP localizes predominantly in the nucleus through the action
      of nuclear localization signals in the repeated regions of the protein. EBNA-LP
      has also been detected in the cytoplasm, and a previous study suggested that some
      of the EBNA-LP coactivation function is mediated by relocalizing histone
      deacetylase 4 (HDAC4) from the nucleus to the cytoplasm. Although EBNA-LP can be
      found in the cytoplasm, it has no obvious nuclear export signal, and there is no
      direct evidence for active shuttling between these cellular compartments. Whether
      active shuttling between the nucleus and cytoplasm is required for coactivation
      remains to be clarified. To address these issues, we tested a variety of EBNA-LP
      isoforms and mutants for nuclear-cytoplasmic shuttling activity in an
      interspecies heterokaryon assay and for the ability to associate with HDAC4. EBNA
      LP isoforms smaller than 42 kDa shuttle efficiently in the heterokaryon assay via
      a crm-1-independent mechanism. In addition, no specific EBNA-LP domain that
      mediates nuclear export could be identified. In contrast, an EBNA-LP 62-kDa
      isoform does not demonstrate detectable shuttling in the heterokaryon assay yet
      still coactivates EBNA2 similarly to the smaller EBNA-LP isoforms. All of the
      EBNA-LP mutants tested, including the coactivation-deficient DeltaCR3 mutant and
      the nonshuttling 62-kDa isoform, were capable of associating with HDAC4. Taken
      together, our results suggest that simple diffusion may account for the nuclear
      export observed with smaller isoforms of EBNA-LP, that nuclear-cytoplasmic
      shuttling is not required for efficient EBNA-LP coactivation function, and that
      competence for HDAC4 association is not sufficient to mediate nuclear-cytoplasmic
      shuttling or EBNA-LP coactivation in the absence of a functional interaction with
      Sp100A.

PMID- 19403676
TI  - Theiler's murine encephalomyelitis virus leader protein is the only nonstructural
      protein tested that induces apoptosis when transfected into mammalian cells.
AB  - Theiler's murine encephalomyelitis virus (TMEV) induces two distinct cell death
      programs, necrosis and apoptosis. The apoptotic pathway is of particular interest
      because TMEV persists in the central nervous system of mice, largely in
      infiltrating macrophages, which undergo apoptosis. Infection of murine
      macrophages in culture induces apoptosis that is Bax dependent through the
      intrinsic or mitochondrial pathway, restricting infectious-virus yields and
      raising the possibility that apoptosis represents a mechanism to attenuate TMEV
      yet promote macrophage-to-macrophage spread during persistent infection. To help
      define the cellular stressors and upstream signaling events leading to apoptosis
      during TMEV infection, we screened baby hamster kidney (BHK-21) cells transfected
      to express individual nonstructural genes (except 3B) of the low-neurovirulence
      BeAn virus strain for cell death. Only expression of the leader protein led to
      apoptosis, as assessed by fluorescence-activated cell sorting analysis of
      propidium iodide- and annexin V-stained transfected cells, immunoblot analysis of
      poly(ADP-ribose) polymerase and caspase cleavages, electron microscopy, and
      inhibition of apoptosis by the pancaspase inhibitor qVD-OPh. After transfection,
      Bak and not Bax expression increased, suggesting that the apical pathway leading
      to activation of these Bcl-2 multi-BH-domain proapoptotic proteins differs in
      BeAn virus infection versus L transfection. Mutation to remove the CHCC Zn finger
      motif from L, a motif required by L to mediate inhibition of nucleocytoplasmic
      trafficking, significantly reduced L-protein-induced apoptosis in both BHK-21 and
      M1-D macrophages.

PMID- 19403677
TI  - Fibrils of prostatic acid phosphatase fragments boost infections with XMRV
      (xenotropic murine leukemia virus-related virus), a human retrovirus associated
      with prostate cancer.
AB  - The xenotropic murine leukemia virus-related virus (XMRV) has recently been
      detected in prostate cancer tissues and may play a role in tumorigenesis. It is
      currently unclear how this virus is transmitted and which factors promote its
      spread in the prostate. We show that amyloidogenic fragments known as semen
      derived enhancer of virus infection (SEVI) originating from prostatic acid
      phosphatase greatly increase XMRV infections of primary prostatic epithelial and
      stromal cells. Hybrid simian/human immunodeficiency chimeric virus particles
      pseudotyped with XMRV envelope protein were used to demonstrate that the
      enhancing effect of SEVI, or of human semen itself, was at the level of viral
      attachment and entry. SEVI enhanced XMRV infectivity but did not bypass the
      requirement for the xenotropic and polytropic retrovirus receptor 1. Furthermore,
      XMRV RNA was detected in prostatic secretions of some men with prostate cancer.
      The fact that the precursor of SEVI is produced in abundance by the prostate
      indicates that XMRV replication occurs in an environment that provides a natural
      enhancer of viral infection, and this may play a role in the spread of this virus
      in the human population.

PMID- 19403678
TI  - Molecular determinants for subcellular localization of the severe acute
      respiratory syndrome coronavirus open reading frame 3b protein.
AB  - Viruses such as hepatitis C and the severe acute respiratory syndrome coronavirus
      (SARS-CoV) encode proteins that are distributed between mitochondria and the
      nucleus, but little is known about the factors that control partitioning between
      these sites. SARS-CoV encodes a unique accessory gene called open reading frame
      (ORF) 3b that, like other unique accessory genes in SARS-CoV, likely contributes
      to viral pathogenicity. The ORF 3b protein is 154 amino acids and is predicted to
      express from the second ORF in subgenomic RNA3. In this report, we have
      characterized the molecular components that regulate intracellular localization
      of the ORF 3b protein. We demonstrate unique shuttling behavior of ORF 3b,
      whereby the protein initially accumulates in the nucleus and subsequently
      translocates to mitochondria. Following nuclear localization, ORF 3b traffics to
      the outer membrane of mitochondria via a predicted amphipathic alpha-helix.
      Additionally, ORF 3b contains a consensus nuclear export sequence, and we
      demonstrate that nuclear export and thus mitochondrial translocation are
      dependent on a leptomycin B-sensitive nuclear export mechanism. We further show
      that ORF 3b inhibits induction of type I interferon induced by retinoic acid
      induced gene 1 and the mitochondrial antiviral signaling protein. Our
      observations provide insights into the cellular localization of ORF 3b that may
      enhance our understanding of the mechanisms by which ORF 3b contributes to SARS
      CoV pathogenesis. The findings reported here reveal that for multilocalized
      proteins, consideration of the spatiotemporal distribution may be crucial for
      understanding viral protein behavior and function.

PMID- 19403680
TI  - Antibodies to the buried N terminus of rhinovirus VP4 exhibit cross-serotypic
      neutralization.
AB  - Development of a vaccine for the common cold has been thwarted by the fact that
      there are more than 100 serotypes of human rhinovirus (HRV). We previously
      demonstrated that the HRV14 capsid is dynamic and transiently displays the buried
      N termini of viral protein 1 (VP1) and VP4. Here, further evidence for this
      "breathing" phenomenon is presented, using antibodies to several peptides
      representing the N terminus of VP4. The antibodies form stable complexes with
      intact HRV14 virions and neutralize infectivity. Since this region of VP4 is
      highly conserved among all of the rhinoviruses, antiviral activity by these anti
      VP4 antibodies is cross-serotypic. The antibodies inhibit HRV16 infectivity in a
      temperature- and time-dependent manner consistent with the breathing behavior.
      Monoclonal and polyclonal antibodies raised against the 30-residue peptide do not
      react with peptides shorter than 24 residues, suggesting that these peptides are
      adopting three-dimensional conformations that are highly dependent upon the
      length of the peptide. Furthermore, there is evidence that the N termini of VP4
      are interacting with each other upon extrusion from the capsid. A Ser5Cys
      mutation in VP4 yields an infectious virus that forms cysteine cross-links in VP4
      when the virus is incubated at room temperature but not at 4 degrees C. The fact
      that all of the VP4s are involved in this cross-linking process strongly suggests
      that VP4 forms specific oligomers upon extrusion. Together these results suggest
      that it may be possible to develop a pan-serotypic peptide vaccine to HRV, but
      its design will likely require details about the oligomeric structure of the
      exposed termini.

PMID- 19403679
TI  - Uncoupling human immunodeficiency virus type 1 Gag and Pol reading frames: role
      of the transframe protein p6* in viral replication.
AB  - Apart from its regulatory role in protease (PR) activation, little is known about
      the function of the human immunodeficiency virus type 1 transframe protein p6* in
      the virus life cycle. p6* is located between the nucleocapsid and PR domains in
      the Gag-Pol polyprotein precursor and is cleaved by PR during viral maturation.
      We have recently reported that the central region of p6* can be extensively
      mutated without abolishing viral infectivity and replication in vitro. However,
      mutagenesis of the entire p6*-coding sequence in the proviral context is not
      feasible without affecting the superimposed frameshift signal or the overlapping
      p1-p6(gag) sequences. To overcome these limitations, we created a novel NL4-3
      derived provirus by displacing the original frameshift signal to the 3' end of
      the gag gene, thereby uncoupling the p6* gene sequence from the p1-p6(gag)
      reading frame. The resulting virus (AL) proved to be replication competent in
      different cell cultures and thus represents an elegant tool for detailed analysis
      of p6* function. Hence, extensive deletions or substitutions were introduced into
      the p6* gene sequence of the AL provirus, and effects on particle release,
      protein processing, and viral infectivity were evaluated. Interestingly, neither
      the deletion of 63% of all p6* residues nor the partial substitution by a
      heterologous sequence affected virus growth and infectivity, suggesting that p6*
      is widely dispensable for viral in vitro replication. However, the insertion of a
      larger reporter sequence interfered with virus production and maturation,
      implying that the length or conformation of this spacer region might be critical
      for p6* function.

PMID- 19403681
TI  - Ebolavirus VP35 interacts with the cytoplasmic dynein light chain 8.
AB  - The viral protein VP35 of ebolavirus (EBOV) is implicated to have diverse roles
      in the viral life cycle. We employed a yeast two-hybrid screen to search for VP35
      binding partners and identified the cytoplasmic dynein light chain (DLC8) as a
      protein that interacts with VP35. Mapping analysis unraveled a consensus motif,
      SQTQT, within VP35 through which VP35 binds to DLC8. The disruption of DLC8
      binding does not affect the ability of VP35 to inhibit type I IFN production.
      Given that VP35 from various EBOV species interacts with DLC8, this interaction
      may have a role in regulating the EBOV life cycle.

PMID- 19403683
TI  - Adaptive mutations resulting in enhanced polymerase activity contribute to high
      virulence of influenza A virus in mice.
AB  - High virulence of influenza virus A/Puerto Rico/8/34 in mice carrying the Mx1
      resistance gene was recently shown to be determined by the viral surface proteins
      and the viral polymerase. Here, we demonstrated high-level polymerase activity in
      mammalian host cells but not avian host cells and investigated which mutations in
      the polymerase subunits PB1, PB2, and PA are critical for increased polymerase
      activity and high virus virulence. Mutational analyses demonstrated that an
      isoleucine-to-valine change at position 504 in PB2 was the most critical and
      strongly enhanced the activity of the reconstituted polymerase complex. An
      isoleucine-to-leucine change at position 550 in PA further contributed to
      increased polymerase activity and high virulence, whereas all other mutations in
      PB1, PB2, and PA were irrelevant. To determine whether this pattern of acquired
      mutations represents a preferred viral strategy to gain virulence, two
      independent new virus adaptation experiments were performed. Surprisingly, the
      conservative I504V change in PB2 evolved again and was the only mutation present
      in an aggressive virus variant selected during the first adaptation experiment.
      In contrast, the virulent virus selected in the second adaptation experiment had
      a lysine-to-arginine change at position 208 in PB1 and a glutamate-to-glycine
      change at position 349 in PA. These results demonstrate that a variety of minor
      amino acid changes in the viral polymerase can contribute to enhanced virulence
      of influenza A virus. Interestingly, all virulence-enhancing mutations that we
      identified in this study resulted in substantially increased viral polymerase
      activity.

PMID- 19403682
TI  - The NS1 protein of a human influenza virus inhibits type I interferon production
      and the induction of antiviral responses in primary human dendritic and
      respiratory epithelial cells.
AB  - The NS1 protein of the influenza A virus is a potent virulence factor that
      inhibits type I interferon (IFN) synthesis, allowing the virus to overcome host
      defenses and replicate efficiently. However, limited studies have been conducted
      on NS1 function using human virus strains and primary human cells. We used NS1
      truncated mutant influenza viruses derived from the human isolate influenza
      A/TX/91 (TX WT, where WT is wild type) to study the functions of NS1 in infected
      primary cells. Infection of primary differentiated human tracheo-bronchial
      epithelial cells with an NS1 truncated mutant demonstrated limited viral
      replication and enhanced type I IFN induction. Additionally, human dendritic
      cells (DCs) infected with human NS1 mutant viruses showed higher levels of
      activation and stimulated naive T-cells better than TX WT virus-infected DCs. We
      also compared infections of DCs with TX WT and our previously characterized
      laboratory strain A/PR/8/34 (PR8) and its NS1 knockout strain, deltaNS1. TX WT
      infected DCs displayed higher viral replication than PR8 but had decreased
      antiviral gene expression at late time points and reduced naive T-cell
      stimulation compared to PR8 infections, suggesting an augmented inhibition of IFN
      production and human DC activation. Our findings show that human-derived
      influenza A viruses have a high capacity to inhibit the antiviral state in a
      human system, and here we have evaluated the possible mechanism of this
      inhibition. Lastly, C-terminal truncations in the NS1 protein of human influenza
      virus are sufficient to make the virus attenuated and more immunogenic,
      supporting its use as a live attenuated influenza vaccine in humans.

PMID- 19403684
TI  - Human immunodeficiency virus type 1 Nef protein targets CD4 to the multivesicular
      body pathway.
AB  - The Nef protein of human immunodeficiency virus type 1 downregulates the CD4
      coreceptor from the surface of host cells by accelerating the rate of CD4
      endocytosis through a clathrin/AP-2 pathway. Herein, we report that Nef has the
      additional function of targeting CD4 to the multivesicular body (MVB) pathway for
      eventual delivery to lysosomes. This targeting involves the endosomal sorting
      complex required for transport (ESCRT) machinery. Perturbation of this machinery
      does not prevent removal of CD4 from the cell surface but precludes its lysosomal
      degradation, indicating that accelerated endocytosis and targeting to the MVB
      pathway are separate functions of Nef. We also show that both CD4 and Nef are
      ubiquitinated on lysine residues, but this modification is dispensable for Nef
      induced targeting of CD4 to the MVB pathway.

PMID- 19403685
TI  - Vaccine-induced cellular responses control simian immunodeficiency virus
      replication after heterologous challenge.
AB  - All human immunodeficiency virus (HIV) vaccine efficacy trials to date have ended
      in failure. Structural features of the Env glycoprotein and its enormous
      variability have frustrated efforts to induce broadly reactive neutralizing
      antibodies. To explore the extent to which vaccine-induced cellular immune
      responses, in the absence of neutralizing antibodies, can control replication of
      a heterologous, mucosal viral challenge, we vaccinated eight macaques with a
      DNA/Ad5 regimen expressing all of the proteins of SIVmac239 except Env. Vaccinees
      mounted high-frequency T-cell responses against 11 to 34 epitopes. We challenged
      the vaccinees and eight naive animals with the heterologous biological isolate
      SIVsmE660, using a regimen intended to mimic typical HIV exposures resulting in
      infection. Viral loads in the vaccinees were significantly less at both the peak
      (1.9-log reduction; P < 0.03) and at the set point (2.6-log reduction; P < 0.006)
      than those in control naive animals. Five of eight vaccinated macaques controlled
      acute peak viral replication to less than 80,000 viral RNA (vRNA) copy eq/ml and
      to less than 100 vRNA copy eq/ml in the chronic phase. Our results demonstrate
      that broad vaccine-induced cellular immune responses can effectively control
      replication of a pathogenic, heterologous AIDS virus, suggesting that T-cell
      based vaccines may have greater potential than previously appreciated.

PMID- 19403688
TI  - Populations at risk--paediatrics.
AB  - Disasters affect all segments of the population. Many subsets of the general
      adult population have specific needs and vulnerabilities. One group with specific
      needs and which is always at high risk in disasters is children. The
      physiological, anatomical, developmental and psychological requirements in
      children differ from those of adults. Disaster planning must recognise and adapt
      to this. For the past 3 years, the Centre of Excellence in Emergency Preparedness
      (CEEP) has been developing a document that will outline specific paediatric
      issues in disasters and provide general (and, where possible, specific)
      guidelines for Canadian health-care providers and disaster planners. This paper
      discusses special issues of emergency preparedness for children and reviews the
      content of the document being developed at CEEP.

PMID- 19403687
TI  - Novel microRNAs (miRNAs) encoded by herpesvirus of Turkeys: evidence of miRNA
      evolution by duplication.
AB  - Herpesviruses account for 134 out of the 140 virus-encoded microRNAs (miRNAs)
      known today. Here we report the identification of 11 novel miRNAs encoded by
      herpesvirus of turkey (HVT), a virus used as a live vaccine in poultry against
      the highly oncogenic Marek's disease virus type 1. Ten of these miRNAs were
      clustered together within the repeat long region of the viral genome,
      demonstrating some degree of positional conservation with other mardiviruses.
      Close sequence and phylogenetic relationships of some miRNAs in this cluster
      indicate evolution by duplication. HVT miRNAs represent the first example of
      virus-encoded miRNAs that show evolution by duplication.

PMID- 19403686
TI  - Quantitative fluorescence resonance energy transfer microscopy analysis of the
      human immunodeficiency virus type 1 Gag-Gag interaction: relative contributions
      of the CA and NC domains and membrane binding.
AB  - The human immunodeficiency virus type 1 structural polyprotein Pr55(Gag) is
      necessary and sufficient for the assembly of virus-like particles on cellular
      membranes. Previous studies demonstrated the importance of the capsid C-terminal
      domain (CA-CTD), nucleocapsid (NC), and membrane association in Gag-Gag
      interactions, but the relationships between these factors remain unclear. In this
      study, we systematically altered the CA-CTD, NC, and the ability to bind membrane
      to determine the relative contributions of, and interplay between, these factors.
      To directly measure Gag-Gag interactions, we utilized chimeric Gag-fluorescent
      protein fusion constructs and a fluorescence resonance energy transfer (FRET)
      stoichiometry method. We found that the CA-CTD is essential for Gag-Gag
      interactions at the plasma membrane, as the disruption of the CA-CTD has severe
      impacts on FRET. Data from experiments in which wild-type (WT) and CA-CTD mutant
      Gag molecules are coexpressed support the idea that the CA-CTD dimerization
      interface consists of two reciprocal interactions. Mutations in NC have less
      severe impacts on FRET between normally myristoylated Gag proteins than do CA-CTD
      mutations. Notably, when nonmyristoylated Gag interacts with WT Gag, NC is
      essential for FRET despite the presence of the CA-CTD. In contrast,
      constitutively enhanced membrane binding eliminates the need for NC to produce a
      WT level of FRET. These results from cell-based experiments suggest a model in
      which both membrane binding and NC-RNA interactions serve similar scaffolding
      functions so that one can functionally compensate for a defect in the other.

PMID- 19403689
TI  - Support for families coping with stroke or dementia: special considerations for
      emergency management.
AB  - Public resilience, an important determinant of effective disaster management, is
      dynamic, and families coping with debilitating illnesses, such as stroke or
      dementia, experience unique vulnerabilities as a result of their caregiving
      responsibilities. When social networks cannot sustain care, family caregivers
      turn to formal respite programmes for support. This has tremendous implications
      on demands for respite services in any disaster response. With an ageing
      population, the demands for family caregiving are increasing, and more people
      face the challenges of balancing work and family responsibilities. This includes
      members of the response community who have family members who need assistance
      with daily living. Without support, many responders may struggle to fulfil their
      professional roles, creating a threat to response capacity. Preparedness
      interventions should focus on building resilience and encourage families to
      explore possibilities for respite care as well as other standard strategies to
      ensure self-sufficiency in the early phases of a disaster.

PMID- 19403690
TI  - Epidermal growth factor-induced contraction regulates paxillin phosphorylation to
      temporally separate traction generation from de-adhesion.
AB  - Directed cell migration is mediated by cycles of protrusion, adhesion, traction
      generation on the extracellular matrix and retraction. However, how the events
      after protrusion are timed, and what dictates their temporal order is completely
      unknown. We used acute epidermal growth factor (EGF) stimulation of epidermal
      keratinocytes to initiate the cell migration cycle to study the mechanism of the
      timing of adhesion, traction generation, and de-adhesion. Using microscopic and
      biochemical assays, we surprisingly found that at approximately 2 min after EGF
      stimulation protrusion, activation of myosin-II, traction generation, adhesion
      assembly, and paxillin phosphorylation occurred nearly simultaneously, followed
      by a 10-min delay during which paxillin became dephosphorylated before cell
      retraction. Inhibition of myosin-II blocked both the EGF-stimulated paxillin
      phosphorylation and cell retraction, and a paxillin phosphomimic blocked
      retraction. These results suggest that EGF-mediated activation of myosin-II acts
      as a mechanical signal to promote a cycle of paxillin
      phosphorylation/dephosphorylation that mediates a cycle of adhesion strengthening
      and weakening that delays cell retraction. Thus, we reveal for the first time a
      mechanism by which cells may temporally segregate protrusion, adhesion, and
      traction generation from retraction during EGF-stimulated cell migration.

PMID- 19403691
TI  - Dynein-driven mitotic spindle positioning restricted to anaphase by She1p
      inhibition of dynactin recruitment.
AB  - Dynein is a minus-end-directed microtubule motor important for mitotic spindle
      positioning. In budding yeast, dynein activity is restricted to anaphase when the
      nucleus enters the bud neck, yet the nature of the underlying regulatory
      mechanism is not known. Here, the microtubule-associated protein She1p is
      identified as a novel regulator of dynein activity. In she1 Delta cells, dynein
      is activated throughout the cell cycle, resulting in aberrant spindle movements
      that misposition the spindle. We also found that dynactin, a cofactor essential
      for dynein motor function, is a dynamic complex whose recruitment to astral
      microtubules (aMTs) increases dramatically during anaphase. Interestingly, loss
      of She1p eliminates the cell-cycle regulation of dynactin recruitment and permits
      enhanced dynactin accumulation on aMTs throughout the cell cycle. Furthermore,
      localization of the dynactin complex to aMTs requires dynein, suggesting that
      dynactin is recruited to aMTs via interaction with dynein and not the microtubule
      itself. Lastly, we present evidence supporting the existence of an incomplete
      dynactin subcomplex localized at the SPB, and a complete complex that is loaded
      onto aMTs from the cytoplasm. We propose that She1p restricts dynein-dependent
      spindle positioning to anaphase by inhibiting the association of dynein with the
      complete dynactin complex.

PMID- 19403692
TI  - BPAG1e maintains keratinocyte polarity through beta4 integrin-mediated modulation
      of Rac1 and cofilin activities.
AB  - alpha6beta4 integrin, a component of hemidesmosomes, also plays a role in
      keratinocyte migration via signaling through Rac1 to the actin-severing protein
      cofilin. Here, we tested the hypothesis that the beta4 integrin-associated plakin
      protein, bullous pemphigoid antigen 1e (BPAG1e) functions as a scaffold for
      Rac1/cofilin signal transduction. We generated keratinocyte lines exhibiting a
      stable knockdown in BPAG1e expression. Knockdown of BPAG1e does not affect
      expression levels of other hemidesmosomal proteins, nor the amount of beta4
      integrin expressed at the cell surface. However, the amount of Rac1 associating
      with beta4 integrin and the activity of both Rac1 and cofilin are significantly
      lower in BPAG1e-deficient cells compared with wild-type keratinocytes. In
      addition, keratinocytes deficient in BPAG1e exhibit loss of front-to-rear
      polarity and display aberrant motility. These defects are rescued by inducing
      expression of constitutively active Rac1 or active cofilin. These data indicate
      that the BPAG1e is required for efficient regulation of keratinocyte polarity and
      migration by determining the activation of Rac1.

PMID- 19403693
TI  - Obscurin interacts with a novel isoform of MyBP-C slow at the periphery of the
      sarcomeric M-band and regulates thick filament assembly.
AB  - Obscurin is a multidomain protein composed of adhesion and signaling domains that
      plays key roles in the organization of contractile and membrane structures in
      striated muscles. Overexpression of the second immunoglobulin domain of obscurin
      (Ig2) in developing myotubes inhibits the assembly of A- and M-bands, but not Z
      disks or I-bands. This effect is mediated by the direct interaction of the Ig2
      domain of obscurin with a novel isoform of myosin binding protein-C slow (MyBP-C
      slow), corresponding to variant-1. Variant-1 contains all the structural motifs
      present in the known forms of MyBP-C slow, but it has a unique COOH terminus.
      Quantitative reverse transcription-polymerase chain reaction indicated that MyBP
      C slow variant-1 is expressed in skeletal muscles both during development and at
      maturity. Immunolabeling of skeletal myofibers with antibodies to the unique COOH
      terminus of variant-1 demonstrated that, unlike other forms of MyBP-C slow that
      reside in the C-zones of A-bands, variant-1 preferentially concentrates around M
      bands, where it codistributes with obscurin. Overexpression of the Ig2 domain of
      obscurin or reduction of expression of obscurin inhibited the integration of
      variant-1 into forming M-bands in skeletal myotubes. Collectively, our
      experiments identify a new ligand of obscurin at the M-band, MyBP-C slow variant
      1 and suggest that their interaction contributes to the assembly of M- and A
      bands.

PMID- 19403694
TI  - Varp is a novel Rab32/38-binding protein that regulates Tyrp1 trafficking in
      melanocytes.
AB  - Two small GTPase Rabs, Rab32 and Rab38, have recently been proposed to regulate
      trafficking of melanogenic enzymes to melanosomes in mammalian epidermal
      melanocytes; however, the exact molecular mechanism of Rab32/38-mediated
      transport of melanogenic enzymes has never been clarified, because no Rab32/38
      specific effector has ever been identified. In this study, we screened for a
      Rab32/38-specific effector by a yeast two-hybrid assay using a guanosine
      triphosphate (GTP)-locked Rab32/38 as bait and found that VPS9-ankyrin-repeat
      protein (Varp)/Ankrd27, characterized previously as a guanine nucleotide exchange
      factor (GEF) for Rab21, functions as a specific Rab32/38-binding protein in mouse
      melanocyte cell line melan-a. Deletion analysis showed that the first ankyrin
      repeat (ANKR1) domain functions as a GTP-dependent Rab32/38-binding domain, but
      that the N-terminal VPS9 domain (i.e., Rab21-GEF domain) does not. Small
      interfering RNA-mediated knockdown of endogenous Varp in melan-a cells caused a
      dramatic reduction in Tyrp1 (tyrosinase-related protein 1) signals from
      melanosomes but did not cause any reduction in Pmel17 signals. Furthermore,
      expression of the ANKR1 domain in melan-a cells also caused a dramatic reduction
      of Tyrp1 signals, whereas the VPS9 domain had no effect. Based on these findings,
      we propose that Varp functions as the Rab32/38 effector that controls trafficking
      of Tyrp1 in melanocytes.

PMID- 19403695
TI  - Dual roles for RHOA/RHO-kinase in the regulated trafficking of a voltage
      sensitive potassium channel.
AB  - Kv1.2 is a member of the Shaker family of voltage-sensitive potassium channels
      and contributes to regulation of membrane excitability. The electrophysiological
      activity of Kv1.2 undergoes tyrosine kinase-dependent suppression in a process
      involving RhoA. We report that RhoA elicits suppression of Kv1.2 ionic current by
      modulating channel endocytosis. This occurs through two distinct pathways, one
      clathrin-dependent and the other cholesterol-dependent. Activation of Rho kinase
      (ROCK) via the lysophosphatidic acid (LPA) receptor elicits clathrin-dependent
      Kv1.2 endocytosis and consequent attenuation of its ionic current. LPA-induced
      channel endocytosis is blocked by the ROCK inhibitor Y27632 or by clathrin RNA
      interference. In contrast, steady-state endocytosis of Kv1.2 in unstimulated
      cells is cholesterol dependent. Inhibition of basal ROCK signaling with Y27632
      increased surface Kv1.2, an effect that persists in the presence of clathrin
      small interfering RNA and that is not additive to the increase in surface channel
      levels elicited by the cholesterol sequestering drug filipin. Temperature block
      experiments show that ROCK affects cholesterol-dependent trafficking by
      modulating the recycling of endocytosed channel back to the plasma membrane. Both
      receptor-stimulated and steady-state Kv1.2 trafficking modulated by RhoA/ROCK
      required the activation of dynamin as well as the ROCK effector Lim-kinase,
      indicating a key role for actin remodeling in RhoA-dependent Kv1.2 regulation.

PMID- 19403696
TI  - Control of protein and sterol trafficking by antagonistic activities of a type IV
      P-type ATPase and oxysterol binding protein homologue.
AB  - The oxysterol binding protein homologue Kes1p has been implicated in nonvesicular
      sterol transport in Saccharomyces cerevisiae. Kes1p also represses formation of
      protein transport vesicles from the trans-Golgi network (TGN) through an unknown
      mechanism. Here, we show that potential phospholipid translocases in the Drs2/Dnf
      family (type IV P-type ATPases [P4-ATPases]) are downstream targets of Kes1p
      repression. Disruption of KES1 suppresses the cold-sensitive (cs) growth defect
      of drs2Delta, which correlates with an enhanced ability of Dnf P4-ATPases to
      functionally substitute for Drs2p. Loss of Kes1p also suppresses a drs2-ts allele
      in a strain deficient for Dnf P4-ATPases, suggesting that Kes1p antagonizes Drs2p
      activity in vivo. Indeed, Drs2-dependent phosphatidylserine translocase
      (flippase) activity is hyperactive in TGN membranes from kes1Delta cells and is
      potently attenuated by addition of recombinant Kes1p. Surprisingly, Drs2p also
      antagonizes Kes1p activity in vivo. Drs2p deficiency causes a markedly increased
      rate of cholesterol transport from the plasma membrane to the endoplasmic
      reticulum (ER) and redistribution of endogenous ergosterol to intracellular
      membranes, phenotypes that are Kes1p dependent. These data suggest a homeostatic
      feedback mechanism in which appropriately regulated flippase activity in the
      Golgi complex helps establish a plasma membrane phospholipid organization that
      resists sterol extraction by a sterol binding protein.

PMID- 19403697
TI  - Clustering of syndecan-4 and integrin beta1 by laminin alpha 3 chain-derived
      peptide promotes keratinocyte migration.
AB  - Syndecans function as receptors for extracellular matrix (ECM) with integrins in
      cell spreading. However, the molecular mechanism of their specific involvement in
      cell migration or in wound healing has not been elucidated yet. Here, we report
      that a synthetic peptide, PEP75, which contains the syndecan-binding sequence of
      the laminin alpha 3LG4 module, induces keratinocyte migration in in vitro and in
      vivo. Soluble PEP75 induced the clustering of syndecan-4 and conformation
      modified integrin beta1 colocalized with syndecan-4 in soluble PEP75-induced
      clusters. Treatment of cells in solution with PEP75 resulted in the exposure of
      the P4G11 antibody epitope of integrin beta1 in immunostaining as well as in flow
      cytometry and augmented integrin beta1-dependent cell adhesion to ECM. Pulldown
      assays demonstrated that PEP75 bound to syndecan-4, but not to integrin beta1. A
      siRNA study revealed a role for syndecan-4 in PEP75-induced up-regulation of
      P4G11 antibody binding and migration of HaCaT cells. We conclude that binding of
      soluble PEP75 to syndecan-4 induces the coupling of integrin beta1, which is
      associated with integrin beta1-conformational changes and activation, and leads
      to keratinocyte migration. To activate integrin function through syndecans could
      be a novel therapeutic approach for chronic wound.

PMID- 19403698
TI  - The class V myosin Myo2p is required for Fus2p transport and actin polarization
      during the yeast mating response.
AB  - Mating yeast cells remove their cell walls and fuse their plasma membranes in a
      spatially restricted cell contact region. Cell wall removal is dependent on
      Fus2p, an amphiphysin-associated Rho-GEF homolog. As mating cells polarize, Fus2p
      GFP localizes to the tip of the mating projection, where cell fusion will occur,
      and to cytoplasmic puncta, which show rapid movement toward the tip. Movement
      requires polymerized actin, whereas tip localization is dependent on both actin
      and a membrane protein, Fus1p. Here, we show that Fus2p-GFP movement is
      specifically dependent on Myo2p, a type V myosin, and not on Myo4p, another type
      V myosin, or Myo3p and Myo5p, type I myosins. Fus2p-GFP tip localization and
      actin polarization in shmoos are also dependent on Myo2p. A temperature-sensitive
      tropomyosin mutation and Myo2p alleles that specifically disrupt vesicle binding
      caused rapid loss of actin patch organization, indicating that transport is
      required to maintain actin polarity. Mutant shmoos lost actin polarity more
      rapidly than mitotic cells, suggesting that the maintenance of cell polarity in
      shmoos is more sensitive to perturbation. The different velocities, differential
      sensitivity to mutation and lack of colocalization suggest that Fus2p and Sec4p,
      another Myo2p cargo associated with exocytotic vesicles, reside predominantly on
      different cellular organelles.

PMID- 19403699
TI  - Normal formation of a subset of intestinal granules in Caenorhabditis elegans
      requires ATP-binding cassette transporters HAF-4 and HAF-9, which are highly
      homologous to human lysosomal peptide transporter TAP-like.
AB  - TAP-like (TAPL; ABCB9) is a half-type ATP-binding cassette (ABC) transporter that
      localizes in lysosome and putatively conveys peptides from cytosol to lysosome.
      However, the physiological role of this transporter remains to be elucidated.
      Comparison of genome databases reveals that TAPL is conserved in various species
      from a simple model organism, Caenorhabditis elegans, to mammals. C. elegans
      possesses homologous TAPL genes: haf-4 and haf-9. In this study, we examined the
      tissue-specific expression of these two genes and analyzed the phenotypes of the
      loss-of-function mutants for haf-4 and haf-9 to elucidate the in vivo function of
      these genes. Both HAF-4 and HAF-9 tagged with green fluorescent protein (GFP)
      were mainly localized on the membrane of nonacidic but lysosome-associated
      membrane protein homologue (LMP-1)-positive intestinal granules from larval to
      adult stage. The mutants for haf-4 and haf-9 exhibited granular defects in late
      larval and young adult intestinal cells, associated with decreased brood size,
      prolonged defecation cycle, and slow growth. The intestinal granular phenotype
      was rescued by the overexpression of the GFP-tagged wild-type protein, but not by
      the ATP-unbound form of HAF-4. These results demonstrate that two ABC
      transporters, HAF-4 and HAF-9, are related to intestinal granular formation and
      some other physiological aspects.

PMID- 19403700
TI  - Anterograde microtubule transport drives microtubule bending in LLC-PK1
      epithelial cells.
AB  - Microtubules (MTs) have been proposed to act mechanically as compressive struts
      that resist both actomyosin contractile forces and their own polymerization
      forces to mechanically stabilize cell shape. To identify the origin of MT
      bending, we directly observed MT bending and F-actin transport dynamics in the
      periphery of LLC-PK1 epithelial cells. We found that F-actin is nearly stationary
      in these cells even as MTs are deformed, demonstrating that MT bending is not
      driven by actomyosin contractility. Furthermore, the inhibition of myosin II
      activity through the use of blebbistatin results in microtubules that are still
      dynamically bending. In addition, as determined by fluorescent speckle
      microscopy, MT polymerization rarely results, if ever, in bending. We suppressed
      dynamic instability using nocodazole, and we observed no qualitative change in
      the MT bending dynamics. Bending most often results from anterograde transport of
      proximal portions of the MT toward a nearly stationary distal tip. Interestingly,
      we found that in an in vitro kinesin-MT gliding assay, MTs buckle in a similar
      manner. To make quantitative comparisons, we measured curvature distributions of
      observed MTs and found that the in vivo and in vitro curvature distributions
      agree quantitatively. In addition, the measured MT curvature distribution is not
      Gaussian, as expected for a thermally driven semiflexible polymer, indicating
      that thermal forces play a minor role in MT bending. We conclude that many of the
      known mechanisms of MT deformation, such as polymerization and acto-myosin
      contractility, play an inconsequential role in mediating MT bending in LLC-PK1
      cells and that MT-based molecular motors likely generate most of the strain
      energy stored in the MT lattice. The results argue against models in which MTs
      play a major mechanical role in LLC-PK1 cells and instead favor a model in which
      mechanical forces control the spatial distribution of the MT array.

PMID- 19403701
TI  - Apratoxin a reversibly inhibits the secretory pathway by preventing
      cotranslational translocation.
AB  - Apratoxin A is a potent cytotoxic marine natural product that rapidly inhibits
      signal transducer and activator of transcription (STAT) 3 phosphorylation by an
      undefined mechanism. We have used biochemical and proteomics approaches to
      illuminate upstream molecular events. Apratoxin A inhibits Janus kinase
      (JAK)/STAT signaling through rapid down-regulation of interleukin 6 signal
      transducer (gp130). Apratoxin A also depletes cancer cells of several cancer
      associated receptor tyrosine kinases by preventing their N-glycosylation, leading
      to their rapid proteasomal degradation. A proteomics approach revealed that
      several proteins in the endoplasmic reticulum, the site of N-glycoprotein
      synthesis, are down-regulated upon apratoxin A exposure. Using in vitro cell free
      systems, we demonstrated that apratoxin A prevents cotranslational translocation
      of proteins destined for the secretory pathway. This process is reversible in
      living cells. Our study indicates that apratoxins are new tools to study the
      secretory pathway and raises the possibility that inhibition of cotranslational
      translocation may be exploited for anticancer drug development.

PMID- 19403702
TI  - Cisplatin-induced DNA damage activates replication checkpoint signaling
      components that differentially affect tumor cell survival.
AB  - Cisplatin and other platinating agents are some of the most widely used
      chemotherapy agents. These drugs exert their antiproliferative effects by
      creating intrastrand and interstrand DNA cross-links, which block DNA
      replication. The cross-links mobilize signaling and repair pathways, including
      the Rad9-Hus1-Rad1-ATR-Chk1 pathway, a pathway that helps tumor cells survive the
      DNA damage inflicted by many chemotherapy agents. Here we show that Rad9 and ATR
      play critical roles in helping tumor cells survive cisplatin treatment. However,
      depleting Chk1 with small interfering RNA or inhibiting Chk1 with 3
      (carbamoylamino)-5-(3-fluorophenyl)-N-(3-piperidyl)thiophene-2-carboxamide
      (AZD7762) did not sensitize these cells to cisplatin, oxaliplatin, or
      carboplatin. Moreover, when Rad18, Rad51, BRCA1, BRCA2, or FancD2 was disabled,
      Chk1 depletion did not further sensitize the cells to cisplatin. In fact, Chk1
      depletion reversed the sensitivity seen when Rad18 was disabled. Collectively,
      these studies suggest that the pharmacological manipulation of Chk1 may not be an
      effective strategy to sensitize tumors to platinating agents.

PMID- 19403703
TI  - Inhibition of aquaporin-1 and aquaporin-4 water permeability by a derivative of
      the loop diuretic bumetanide acting at an internal pore-occluding binding site.
AB  - Aquaporin (AQP) water channels, essential for fluid homeostasis, are expressed in
      perivascular brain end-feet regions of astroglia (AQP4) and in choroid plexus
      (AQP1). At a high concentration, the loop diuretic bumetanide has been shown to
      reduce rat brain edema after ischemic stroke by blocking Na(+)-K(+)-2Cl(-)
      cotransport. We hypothesized that an additional inhibition of AQP contributes to
      the protection. We show that osmotic water flux in AQP4-expressing Xenopus laevis
      oocytes is reduced by extracellular bumetanide (> or =100 microM). The efficacy
      of block by bumetanide is increased by injection intracellularly. Forty-five
      synthesized bumetanide derivatives were tested on oocytes expressing human AQP1
      and rat AQP4. Of these, one of the most effective was the 4-aminopyridine
      carboxamide analog, AqB013, which inhibits AQP1 and AQP4 (IC(50) approximately 20
      microM, applied extracellularly). The efficacy of block was enhanced by
      mutagenesis of intracellular AQP4 valine-189 to alanine (V189A, IC(50)
      approximately 8 microM), confirming the aquaporin as the molecular target of
      block. In silico docking of AqB013 supported an intracellular candidate binding
      site in rat AQP4 and suggested that the block involves occlusion of the AQP water
      pore at the cytoplasmic side. AqB013 at 2 microM had no effect, and 20 microM
      caused 20% block of human Na(+)-K(+)-2Cl(-) cotransporter activity, in contrast
      to >90% block of the transporter by bumetanide. AqB013 did not affect X. laevis
      oocyte Cl(-) currents and did not alter rhythmic electrical conduction in an ex
      vivo gastric muscle preparation. The identification of AQP-selective
      pharmacological agents opens opportunities for breakthrough strategies in the
      treatment of edema and other fluid imbalance disorders.

PMID- 19403704
TI  - Funding food science and nutrition research: financial conflicts and scientific
      integrity.
AB  - There has been substantial public debate about the susceptibility of research to
      biases of various kinds. The dialogue has extended to the peer-reviewed
      literature, scientific conferences, the mass media, government advisory bodies,
      and beyond. While biases can come from myriad sources, the overwhelming focus of
      the discussion, to date, has been on industry-funded science. Given the critical
      role that industry has played and will continue to play in the research process,
      the International Life Sciences Institute (ILSI) North America Working Group on
      Guiding Principles has, in this paper, set out proposed conflict-of-interest
      guidelines regarding industry funding for protecting the integrity and
      credibility of the scientific record, particularly with respect to health,
      nutrition, and food safety science. Eight principles are enumerated, specifying
      ground rules for industry-sponsored research. The paper, which issues a challenge
      to the broader scientific community to address all bias issues, is only a first
      step; the document is intended to be dynamic, prompting ongoing discussion and
      refinement.

PMID- 19403706
TI  - Fructose and satiety.
AB  - A role for the increased intake of dietary fructose in general and high-fructose
      corn syrup (HFCS) in particular in the current obesity epidemic has been
      proposed. Consumed fructose and glucose have different rates of gastric emptying,
      are differentially absorbed from the gastrointestinal tract, result in different
      endocrine profiles, and have different metabolic fates, providing multiple
      opportunities for the 2 saccharides to differentially affect food intake. The
      consequences of fructose and glucose on eating have been studied under a variety
      of experimental situations in both model systems and man. The results have been
      inconsistent, and the particular findings appear to depend on the timing of
      saccharide administration or ingestion relative to a test meal situation, whether
      the saccharides are administered as pure sugars or as components of a dietary
      preload, and the overall volume of the preload. These factors rather than
      intrinsic differences in the saccharides' ability to induce satiety appear to
      carry many of the differential effects on food intake that have been found. On
      balance, the case for fructose being less satiating than glucose or HFCS being
      less satiating than sucrose is not compelling.

PMID- 19403705
TI  - Dietary fructose and glucose differentially affect lipid and glucose homeostasis.
AB  - Absorbed glucose and fructose differ in that glucose largely escapes first-pass
      removal by the liver, whereas fructose does not, resulting in different metabolic
      effects of these 2 monosaccharides. In short-term controlled feeding studies,
      dietary fructose significantly increases postprandial triglyceride (TG) levels
      and has little effect on serum glucose concentrations, whereas dietary glucose
      has the opposite effects. When dietary glucose and fructose have been directly
      compared at approximately 20-25% of energy over a 4- to 6-wk period, dietary
      fructose caused significant increases in fasting TG and LDL cholesterol
      concentrations, whereas dietary glucose did not, but dietary glucose did increase
      serum glucose and insulin concentrations in the postprandial state whereas
      dietary fructose did not. When fructose at 30-60 g ( approximately 4-12% of
      energy) was added to the diet in the free-living state, there were no significant
      effects on lipid or glucose biomarkers. Sucrose and high-fructose corn syrup
      (HFCS) contain approximately equal amounts of fructose and glucose and no
      metabolic differences between them have been noted. Controlled feeding studies at
      more physiologic dietary intakes of fructose and glucose need to be conducted. In
      our view, to decrease the current high prevalence of obesity, dyslipidemia,
      insulin resistance, and diabetes, the focus should be on restricting the intake
      of excess energy, sucrose, HFCS, and animal and trans fats and increasing
      exercise and the intake of vegetables, vegetable oils, fish, fruit, whole grains,
      and fiber.

PMID- 19403708
TI  - Dietary and endogenous amino acids are the main contributors to microbial protein
      in the upper gut of normally nourished pigs.
AB  - Although amino acids (AA) synthesized by enteric microbiota in the upper gut of
      nonruminants can be absorbed, they do not necessarily make a net contribution to
      the host's AA supply. That depends on whether protein or nonprotein nitrogen
      sources are used for microbial protein production. We determined the
      contributions of urea, endogenous protein (EP), and dietary protein (DP) to
      microbial valine (M.VAL) at the distal ileum of growing pigs, based on isotope
      dilutions after a 4-d continuous infusion of l-[1-(13)C]valine to label EP and of
      [(15)N(15)N]urea. Eight barrows were assigned to either a cornstarch and soybean
      meal-based diet with or without 12% added fermentable fiber from pectin. Dietary
      pectin did not affect (P > 0.10) the contributions of the endogenous and DP to
      M.VAL. More than 92% of valine in microbial protein in the upper gut was derived
      from preformed AA from endogenous and DP, suggesting that de novo synthesis makes
      only a small contribution to microbial AA.

PMID- 19403709
TI  - The effect of high-fructose corn syrup consumption on triglycerides and uric
      acid.
AB  - Rates of overweight and obesity have been on a steady rise for decades, and the
      problems society faces from this and associated metabolic diseases are many. As a
      result, the need to understand the contributing factors is great. A very
      compelling case can be made that excess sugar consumption has played a
      significant role. In addition, fructose, as a component of the vast majority of
      caloric sweeteners, is seen to be particularly insidious. Evidence shows that
      fructose bypasses many of the body's satiating signals, thus potentially
      promoting overconsumption of energy, weight gain, and the development on insulin
      resistance. It has also been shown to increase uric acid levels, which in turn
      promotes many of the abnormalities seen in the metabolic syndrome including
      hypertriglyceridemia. However, the main source of fructose in the diet is high
      fructose corn syrup (HFCS), an artificially manufactured disaccharide that is
      only 55% fructose. This review highlights the fact that limited data are
      available about the metabolic effects of HFCS compared with other caloric
      sweeteners. The data suggest that HFCS yields similar metabolic responses to
      other caloric sweeteners such as sucrose.

PMID- 19403707
TI  - Vitamin E reverses impaired linker for activation of T cells activation in T
      cells from aged C57BL/6 mice.
AB  - Supplemental vitamin E alleviates age-related defects in interleukin (IL)-2
      production, T cell proliferation, and immune synapse formation. Here, we
      evaluated the effect of in vitro supplementation with 46 mumol/L of vitamin E on
      T cell receptor-proximal signaling events of CD4(+) T cells from young (4-6 mo)
      and old (22-26 mo) C57BL mice. Aged murine CD4(+) T cells stimulated via CD3 and
      CD28, tyrosine 191 of the adaptor protein Linker for Activation of T cells (LAT),
      was hypo-phosphorylated. Supplementation with vitamin E eliminated this
      difference in the tyrosine phosphorylation of LAT. By using a flow cytometric
      assay, the age-related differences in the activation-induced phosphorylation of
      LAT were observed in both naive and memory T cell subsets. In addition,
      supplementation with vitamin E eliminates the age-related differences in LAT
      phosphorylation in both T cell subsets. Neither age nor vitamin E supplementation
      altered the fraction of LAT entering the membrane compartment. Furthermore,
      neither age nor vitamin E influenced the phosphorylation of Lck and Zap70,
      indicating that associated changes in LAT phosphorylation were not caused by
      alterations in activation states of the upstream kinases Lck and Zap70.

PMID- 19403710
TI  - Periconceptional iron and folate status is inadequate among married, nulliparous
      women in rural Bangladesh.
AB  - Recent evidence suggests that poor fetal growth is associated with preconception
      anemia and first trimester iron deficiency. Periconceptional iron and folate
      supplementation may improve the effectiveness of iron supplementation programs
      during pregnancy by treating preexisting anemia, building iron stores, and
      reducing risk of neural tube defects. Our objective in this study was to describe
      the iron and folate status of married, nulliparous women in rural Bangladesh from
      March to May 2007. Of 272 women, 37% were anemic (hemoglobin <120 g/L), 13% were
      folate deficient (plasma folate <or=10 nmol/L), 15% were iron deficient (plasma
      ferritin <12 microg/L or tranferrin receptor >4.4 mg/L), 11% were iron deficient
      and anemic, and 81% were estimated to have <500 mg of iron stores. Risk of anemia
      was 4 times greater among nonstudents than students (95% CI: 1.23, 14.69), twice
      as likely among women with a previous miscarriage compared with those who had
      never been pregnant (95% CI: 1.04, 5.47), and 6 times greater among iron
      deficient compared to iron-replete women (95% CI: 2.76, 11.81). Adolescents
      (<or=19 y) had lower mean plasma ferritin concentration (38.3 +/- SD vs. 49.1 +/-
      SD microg/L; P = 0.004) and body iron stores [3.4 +/- 5.2 mg/kg vs. 4.3 +/- 5.6
      mg/kg (0.06 +/- 0.09 mmol/kg vs. 0.08 +/- 0.10 mmol/kg); P = 0.006] compared with
      adults. An unacceptably high percentage of nulliparous women in rural Bangladesh
      have inadequate iron and folate status. As they enter pregnancy, more than one
      third will be anemic, >80% will have inadequate iron stores, and more than one
      tenth will be folate deficient. Further research is needed on risk factors of
      poor nutritional status before the start of a woman's childbearing years.

PMID- 19403711
TI  - Urinary iodine concentrations indicate iodine deficiency in pregnant Thai women
      but iodine sufficiency in their school-aged children.
AB  - The median urinary iodine concentration (UI) in school-aged children is
      recommended for assessment of iodine nutrition in populations. If the median UI
      is adequate in school-aged children, it is usually assumed iodine intakes are
      also adequate in the remaining population, including pregnant women. But iodine
      requirements sharply increase during pregnancy. In this study, our aim was to
      measure UI in pairs of pregnant women and their school-aged children from the
      same family, who were sharing meals, to directly assess whether a household food
      basket that supplies adequate iodine to school-aged children also meets the needs
      of pregnant women. UI was measured in spot urine samples from pairs (n = 302) of
      healthy pregnant mothers and their school-aged children in metropolitan Bangkok,
      Thailand. A dietary questionnaire was completed. The UI [median (range)] in the
      pregnant women {108 (11-558) microg/L [0.85 (0.086-4.41) micromol/L]} were lower
      than those of their school-aged children {200 (25-835) microg/L [1.58 (0.20-6.52)
      micromol/L]} (P < 0.001), indicating optimal iodine status in the children but
      mild-to-moderate iodine deficiency in their pregnant mothers. The estimated
      iodine intakes in the 2 groups were in the range of 130-170 microg/d. There was a
      modest positive correlation between UI in the pairs (r = 0.253; P < 0.01). A
      higher frequency of seafood meals was a significant predictor of UI in both
      groups, but household use of iodized salt was not. These data suggest the median
      UI in school-aged children should not be used as a surrogate for monitoring
      iodine status in pregnancy in central Thailand; pregnant women should be directly
      monitored.

PMID- 19403713
TI  - Food insecurity is not associated with childhood obesity as assessed using
      multiple measures of obesity.
AB  - There has been extensive previous research examining the connection between
      obesity and food insecurity, 2 serious nutrition challenges facing low-income
      children in the US. All of this work used BMI to categorize a child as obese.
      Although BMI is one way to categorize the obesity status of a child, other
      measures have not been used to understand the connection between food insecurity
      and obesity. In response, this study used multiple measures of obesity taken from
      the 2001 to 2004 NHANES. The sample included 2516 children between the ages of 8
      and 17 y in households with annual incomes <200% of the poverty line. Within this
      sample, 36.6% of children were in food-insecure households. The prevalence of
      obesity depended on the measure employed (BMI, waist circumference, triceps
      skinfold thickness, trunk fat mass, body fat), with prevalence rates ranging from
      15.4 to 44.8%. Logistic regression models estimated the probability of a child
      being obese using multiple measures of obesity conditional on food-insecurity
      status and other covariates. The results indicated that food-insecure children
      were no more likely to be obese than their food-secure counterparts across all
      measures of obesity. This relationship held after controlling for other factors
      and examining subpopulations based on race/ethnicity, gender, and race/ethnicity
      and gender. These results suggest that efforts to alleviate food insecurity and
      childhood obesity will work independently.

PMID- 19403714
TI  - High rates of mammary tissue protein turnover in lactating goats are
      energetically costly.
AB  - The high energetic demands and metabolism of amino acids (AA) within the
      lactating mammary gland have been ascribed to the requirements for milk component
      synthesis and tissue maintenance. Our objective in this work was to assess rates
      of protein synthesis from several AA so that the energetic costs of tissue
      maintenance could be better reflected. Lactating goats (n = 4) were given
      staggered infusions of 5 labeled forms of phenylalanine (Phe) initiated at 30,
      12, 9, 6, and 3 h before goats were killed. [5-(13)CH(3)] Methionine (Met), [1
      (13)C] leucine, and [1-(13)C] valine were also infused for 30 h, during which
      time, the glands were milked hourly and arteriovenous flux measurements were
      performed the last 6 h. A dynamic, compartmental model capable of simulating
      fluxes of AA through extracellular and intracellular free, slow and fast turnover
      tissue-bound, and milk protein pools was developed and fitted to the observed
      data. The udder removed 81% of the Phe present in plasma using 31% for milk
      protein synthesis and releasing 66% back into plasma. Transamination accounted
      for 40% of Phe flux in the mammary and transmethylation accounted for a portion
      of mammary Met flux. Mammary tissue protein synthesis was >300% the value of milk
      protein synthesis with fractional protein synthesis rates >130%/d. Assuming 4 mol
      of ATP/mol of peptide bond formed, we estimate that approximately 50% of ATP
      generated by the lactating mammary glands is used for synthesis of tissue
      (nonmilk) protein.

PMID- 19403712
TI  - Fructose consumption: considerations for future research on its effects on
      adipose distribution, lipid metabolism, and insulin sensitivity in humans.
AB  - Results from a recent study investigating the metabolic effects of consuming
      fructose-sweetened beverages at 25% of energy requirements for 10 wk demonstrate
      that a high-fructose diet induces dyslipidemia, decreases insulin sensitivity,
      and increases visceral adiposity. The purpose of this review is to present
      aspects of the study design which may be critical for assessment of the metabolic
      effects of sugar consumption. Collection of postprandial blood samples is
      required to document the full effects of fructose on lipid metabolism. Fasting
      triglyceride (TG) concentrations are an unreliable index of fructose-induced
      dyslipidemia. Differences in the short-term (24-h) and long-term (>2 wk) effects
      of fructose consumption on TG and apolipoprotein-B demonstrate that acute effects
      can differ substantially from those occurring after sustained fructose exposure.
      Investigating the effects of fructose when consumed ad libitum compared with
      energy-balanced diets suggest that additive effects of fructose-induced de novo
      lipogenesis and positive energy balance may contribute to dyslipidemia and
      decreased insulin sensitivity. Increases of intra-abdominal fat observed in
      subjects consuming fructose, but not glucose, for 10 wk indicate that the 2
      sugars have differential effects on regional adipose deposition. However, the
      increase of fasting glucose, insulin, and homeostasis model assessment-insulin
      resistance at 2 wk and the lack of increase of 24-h systemic FFA concentrations
      suggest that fructose decreases insulin sensitivity independently of visceral
      adiposity and FFA. The lower postprandial glucose and insulin excursions in
      subjects consuming fructose and increased excursions in those consuming glucose
      do not support a relationship between dietary glycemic index and the development
      of dyslipidemia, decreased insulin sensitivity, or increased visceral adiposity.

PMID- 19403715
TI  - The leucine content of a complete meal directs peak activation but not duration
      of skeletal muscle protein synthesis and mammalian target of rapamycin signaling
      in rats.
AB  - This study examined the impact of leucine (Leu) derived from complete meals on
      stimulation of skeletal muscle protein synthesis (MPS). Expt. 1 examined time
      course changes in translation initiation and MPS after a meal. Male rats (
      approximately 300 g) were trained for 5 d to eat 3 meals/d providing 20, 50, and
      30% of energy from whey protein, carbohydrates, and fats, respectively. Plasma
      and skeletal muscle were collected at time 0 (baseline) after 12 h of food
      deprivation and then at 45, 90, 135, 180, and 300 min after a 4-g meal. Plasma
      Leu increased at 45 min and remained elevated through 180 min. MPS peaked at 45
      90 min and returned to baseline by 180 min. Plasma Leu correlated with
      phosphorylation of ribosomal protein p70 S6 kinase (r = 0.723; P < 0.05),
      eukaryotic initiation factor 4E binding protein-1 (r = 0.773; P < 0.05), and MPS
      (r = 0.608; P < 0.05) over time. Expt. 2 examined 3 levels of protein intake (10,
      20, and 30% of energy) from 2 sources (wheat and whey) with different Leu
      contents ( approximately 6.8 and approximately 10.9%, respectively) on
      stimulation of initiation and MPS. Rats were trained to eat 3 meals/d providing
      14, 56, and 30% of energy from protein, carbohydrates, and fats. On d 6, MPS was
      evaluated at 90 min after rats consumed 1 of the 6 test meals. Whey protein
      stimulated initiation and MPS more than wheat and the differential response
      related to greater plasma Leu responses in the whey groups. These studies
      demonstrate that peak activation but not duration of MPS is proportional to the
      Leu content of a meal.

PMID- 19403716
TI  - National estimates of dietary fructose intake increased from 1977 to 2004 in the
      United States.
AB  - Our purpose was to conduct a new analysis to update and extend previously
      published trends of fructose availability and estimated fructose intake and food
      sources of dietary fructose from the 1977-1978 Nationwide Food Consumption Survey
      (NFCS) data. We estimated fructose usual intake with data from NHANES 1999-2004
      for 25,165 individuals (1 y and older, excluding pregnant and lactating women and
      breast-fed infants) using the Iowa State C-SIDE software. We applied food group
      specific conversion factors to individual measures of sugar intakes following the
      earlier study. Sweetener availability in the United States increased from 1978,
      peaked in 1999, and declined through 2005. The high-fructose corn syrup
      percentage of sweeteners increased from 16% in 1978 to 42% in 1998 and then
      stabilized. Since 1978, mean daily intakes of added and total fructose increased
      in all gender and age groups, whereas naturally occurring (N) fructose intake
      decreased or remained constant. Total fructose intake as percentage of energy and
      as percentage of carbohydrate increased 1 and 1.2%, whereas daily energy and
      carbohydrate intakes increased 18 and 41%, respectively. Similar to 1978 results,
      nonalcoholic beverages and grain products were the principal food sources of
      added fructose. Fruits and fruit products were the main dietary sources of N
      fructose in 2004; in 1978, grain products and vegetables were more predominant
      food sources. Although comparison of estimates of fructose intakes between data
      from the 1977-1978 NFCS and the NHANES 1999-2004 showed an increase, this
      increase was dwarfed by greater increases in total daily energy and carbohydrate
      intakes.

PMID- 19403717
TI  - Linseed oil in the maternal diet during gestation and lactation modifies fatty
      acid composition, mucosal architecture, and mast cell regulation of the ileal
      barrier in piglets.
AB  - In this study, we investigated the effect of supplementation of the maternal diet
      with linseed oil [rich in 18:3(n-3)] on fatty acid composition, mucosal
      architecture, and mast cell regulation of barrier function in piglet ileum.
      Sixteen sows were fed a lard (LAR)- or a linseed oil (LSO)-based diet during
      gestation and lactation. Fatty acid composition of maternal RBC at parturition
      and of milk at d 14 of lactation were determined. Fatty acid composition, villous
      crypt structure, and permeability to horseradish peroxidase in Ussing chambers
      after mast cell degranulation were determined in the ileum of piglets at d 0, 7,
      and 28. At d 0, 18:3(n-3) and 20:5(n-3) levels were higher, but 22:6(n-3) and
      20:4(n-6) levels were lower in both maternal RBC and piglet ileum of the LSO
      group. Levels of 18:3(n-3) were also higher in the milk of LSO sows. Levels of
      18:3(n-3) were higher in LSO piglet ileum at d 7 and 28. Moreover, at d 28,
      20:4(n-6) ileal levels tended (P = 0.09) to be lower in LSO than in LAR piglets,
      in parallel with a lower mRNA expression of Delta5 desaturase. LSO piglets had
      shorter villi at d 0 and shorter crypts at d 7 compared with LAR piglets. The
      effect of mast cell degranulation on ileal permeability decreased with age in
      both groups but reached a minimum sooner in the LSO group (d 7) than in the LAR
      group (d 28). In conclusion, linseed oil supplementation of the maternal diet
      profoundly modifies the fatty acid composition, structure, and physiology of the
      offspring ileum.

PMID- 19403718
TI  - Retinoic acid is present in the postnatal rat olfactory organ and persists in
      vitamin A--depleted neural tissue.
AB  - Vitamin A (VA), all-trans-retinol (at-ROL), and its derivative, all-trans
      retinoic acid (at-RA), are required for neuron development. The effects of these
      retinoids are dependent upon the nutritional status of the rat and tissue
      specific dynamics of retinoid access and utilization. The purpose of this study
      was to determine the status of at-ROL and at-RA in the peripheral olfactory organ
      of postnatal rats fed a normal diet and rats fed a VA-deficient (VAD) diet.
      Extracted retinoids were analyzed by HPLC. Resolved sample peaks were identified
      by comparing their elution times and spectra with those of authentic standards.
      Mean at-RA and at-ROL concentrations of 23 pmol/g olfactory tissue and 0.13
      nmol/g, respectively, were recovered from olfactory tissue. The ratio of at-RA:at
      ROL in olfactory was approximately 2 times that in testis and 200 times that in
      liver. at-ROL was depleted from the liver and olfactory organ of rats fed a VAD
      diet from birth to 70 d of age. Surprisingly, at-RA was still present in
      olfactory tissue from these rats. At 90 d of age, the VAD rats were frankly
      deficient and at-RA was no longer detectable in olfactory tissue. The
      comparatively high ratio of at-RA:at-ROL in the peripheral olfactory organ and
      the persistence of at-RA in at-ROL-depleted tissues strongly suggests that
      maintenance of local stores of at-RA is functionally relevant in this tissue.

PMID- 19403719
TI  - A plant stanol yogurt drink alone or combined with a low-dose statin lowers serum
      triacylglycerol and non-HDL cholesterol in metabolic syndrome patients.
AB  - We evaluated the effects of 2 commonly available strategies (plant stanol ester
      drink and 10 mg simvastatin) on coronary heart disease (CHD) risk variables in
      participants with metabolic syndrome. Metabolic syndrome patients are at
      increased risk to develop CHD, partly due to high triacylglycerol (TAG) and low
      HDL cholesterol (HDL-C) concentrations and a low-grade inflammatory profile.
      Effects of plant stanol esters on TAG concentrations in these participants are
      unknown. After a 3-wk run-in period in which individuals consumed placebo yogurt
      drinks and placebo capsules, participants were randomly divided into 4 groups:
      placebo (n = 9), simvastatin + placebo drink (n = 10), placebo + stanol drink (n
      = 9), and simvastatin + stanol drink (n = 8). After 9 wk, we evaluated the
      effects on serum lipids, low-grade inflammation, and endothelial dysfunction
      markers. In metabolic syndrome patients, stanol esters (2.0 g/d), simvastatin, or
      the combination lowered non-HDL-C by 12.8% (P = 0.011), 30.7% (P < 0.001), and
      35.4% (P < 0.001), respectively, compared with placebo. TAG were lowered by 27.5%
      (P = 0.044), 21.7% (P = 0.034), and 32.7% (P < 0.01), respectively. The total
      :HDL-C ratio was significantly lowered in all 3 intervention groups. We found no
      treatment effects on the apolipoprotein CII:CIII ratio, cholesterol ester
      transfer protein mass, FFA concentrations, and markers for low-grade inflammation
      or endothelial dysfunction. This study shows that in metabolic syndrome patients,
      plant stanol esters lower not only non-HDL-C, but also TAG. Effects on TAG were
      also present in combination with statin treatment, illustrating an additional
      benefit of stanol esters in this CHD risk population.

PMID- 19403720
TI  - The bioavailability of apigenin-7-glucoside is influenced by human intestinal
      microbiota in rats.
AB  - We investigated the impact of human intestinal microbiota on bioavailability of
      the flavone apigenin-7-glucoside (A7G) by comparing germ-free and human
      microbiota-associated (HMA) rats. First, the ability of the human intestinal
      microbiota to convert A7G was proven in vitro by incubating A7G with fecal
      suspensions. Apigenin, naringenin, and 3-(4-hydroxyphenyl)propionic acid were
      formed as main metabolites. After application of A7G to germ-free rats, apigenin,
      luteolin, and their conjugates were detected in urine and feces. In HMA rats,
      naringenin, eriodictyol, phloretin, 3-(3,4-dihydroxyphenyl)propionic acid, 3-(4
      hydroxyphenyl)propionic acid, 3-(3-hydroxyphenyl)propionic acid, and 4
      hydroxycinnamic acid in their free and conjugated forms were additionally formed.
      In whole-blood samples from germ-free and HMA rats, only apigenin conjugates and
      phloretin, respectively, were detected. The total excretion of A7G and its
      metabolites within 48 h was similarly low in both germ-free and HMA rats, with 11
      and 13% of the A7G dose, respectively. In germ-free rats, A7G metabolites
      dominated by apigenin and its conjugates were mainly excreted with feces. In
      contrast, the compounds in HMA rats were predominantly recovered from urine, 3-(4
      hydroxyphenyl)propionic acid being the main metabolite. The ability of selected
      gut bacteria and the host intestinal mucosa to deglycosylate A7G was tested using
      cell extracts. Apigenin was formed by cytosolic extracts of Eubacterium ramulus
      and Bacteroides distasonis and by the microsomal fraction of the small intestinal
      mucosa of rats. Overall, human intestinal microbiota largely contributed to A7G
      metabolism, indicating its influence on the bioactivity of flavones.

PMID- 19403721
TI  - The intention to treat principle, and the potential impact of excluding data from
      the analysis of clinical trial data.

PMID- 19403722
TI  - Xanthones from mangosteen prevent lipopolysaccharide-mediated inflammation and
      insulin resistance in primary cultures of human adipocytes.
AB  - The xanthones, alpha- and gamma-mangostin (MG), are major bioactive compounds
      found in mangosteen and are reported to have antiinflammatory properties in
      several murine models. Given the association between obesity, chronic low-grade
      inflammation, and insulin resistance, we examined the effects of alpha- and gamma
      MG on markers of inflammation and insulin resistance in primary cultures of newly
      differentiated human adipocytes treated with lipopolysaccharide (LPS). alpha- and
      gamma-MG decreased the induction by LPS of inflammatory genes, including tumor
      necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, monocyte
      chemoattractant protein-1, and Toll-like receptor-2. Moreover, alpha- and gamma
      MG attenuated LPS activation of the mitogen-activated protein kinases (MAPK) c
      jun NH(2)-terminal kinase, extracellular signal-related kinase, and p38. alpha-
      and gamma-MG also attenuated LPS activation of c-Jun and activator protein (AP)-1
      activity. gamma-MG was more effective than alpha-MG on an equimolar basis.
      Furthermore, gamma-MG but not alpha-MG attenuated LPS-mediated IkappaB-alpha
      degradation and nuclear factor-kappaB (NF-kappaB) activity. In addition, gamma-MG
      prevented the suppression by LPS of insulin-stimulated glucose uptake and PPAR
      gamma and adiponectin gene expression. Taken together, these data demonstrate
      that MG attenuates LPS-mediated inflammation and insulin resistance in human
      adipocytes, possibly by inhibiting the activation of MAPK, NF-kappaB, and AP-1.

PMID- 19403723
TI  - Dietary fructose and metabolic syndrome and diabetes.
AB  - Studies in both healthy and diabetic subjects demonstrated that fructose produced
      a smaller postprandial rise in plasma glucose and serum insulin than other common
      carbohydrates. Substitution of dietary fructose for other carbohydrates produced
      a 13% reduction in mean plasma glucose in a study of type 1 and type 2 diabetic
      subjects. However, there is concern that fructose may aggravate lipemia. In 1
      study, day-long plasma triglycerides in healthy men were 32% greater while they
      consumed a high-fructose diet than while they consumed a high-glucose diet. There
      is also concern that fructose may be a factor contributing to the growing
      worldwide prevalence of obesity. Fructose stimulates insulin secretion less than
      does glucose and glucose-containing carbohydrates. Because insulin increases
      leptin release, lower circulating insulin and leptin after fructose ingestion
      might inhibit appetite less than consumption of other carbohydrates and lead to
      increased energy intake. However, there is no convincing experimental evidence
      that dietary fructose actually does increase energy intake. There is also no
      evidence that fructose accelerates protein glycation. High fructose intake has
      been associated with increased risk of gout in men and increased risk of kidney
      stones. Dietary fructose appears to have adverse effects on postprandial serum
      triglycerides, so adding fructose in large amounts to the diet is undesirable.
      Glucose may be a suitable replacement sugar. The fructose that occurs naturally
      in fruits and vegetables provides only a modest amount of dietary fructose and
      should not be of concern.

PMID- 19403724
TI  - The role of diglycosyl lipids in photosynthesis and membrane lipid homeostasis in
      Arabidopsis.
AB  - The galactolipid digalactosyldiacylglycerol (DGD) is an abundant thylakoid lipid
      in chloroplasts. The introduction of the bacterial lipid
      glucosylgalactosyldiacylglycerol (GGD) from Chloroflexus aurantiacus into the DGD
      deficient Arabidopsis (Arabidopsis thaliana) dgd1 mutant was previously shown to
      result in complementation of growth, but photosynthetic efficiency was only
      partially restored. Here, we demonstrate that GGD accumulation in the double
      mutant dgd1dgd2, which is totally devoid of DGD, also complements growth at
      normal and high-light conditions, but photosynthetic efficiency in the GGD
      containing dgd1dgd2 line remains decreased. This is attributable to an increased
      susceptibility of photosystem II to photodamage, resulting in reduced photosystem
      II accumulation already at normal light intensities. The chloroplasts of dgd1 and
      dgd1dgd2 show alterations in thylakoid ultrastructure, a phenotype that is
      restored in the GGD-containing lines. These data suggest that the strong growth
      retardation of the DGD-deficient lines dgd1 and dgd1dgd2 can be primarily
      attributed to a decreased capacity for chloroplast membrane assembly and
      proliferation and, to a smaller extent, to photosynthetic deficiency. During
      phosphate limitation, GGD increases in plastidial and extraplastidial membranes
      of the transgenic lines to an extent similar to that of DGD in the wild type,
      indicating that synthesis and transport of the bacterial lipid (GGD) and of the
      authentic plant lipid (DGD) are subject to the same mechanisms of regulation.

PMID- 19403726
TI  - Regulation of a chemical defense against herbivory produced by symbiotic fungi in
      grass plants.
AB  - Neotyphodium uncinatum and Neotyphodium siegelii are fungal symbionts
      (endophytes) of meadow fescue (MF; Lolium pratense), which they protect from
      insects by producing loline alkaloids. High levels of lolines are produced
      following insect damage or mock herbivory (clipping). Although loline alkaloid
      levels were greatly elevated in regrowth after clipping, loline-alkaloid
      biosynthesis (LOL) gene expression in regrowth and basal tissues was similar to
      unclipped controls. The dramatic increase of lolines in regrowth reflected the
      much higher concentrations in young (center) versus older (outer) leaf blades, so
      LOL gene expression was compared in these tissues. In MF-N. siegelii, LOL gene
      expression was similar in younger and older leaf blades, whereas expression of N.
      uncinatum LOL genes and some associated biosynthesis genes was higher in younger
      than older leaf blades. Because lolines are derived from amino acids that are
      mobilized to new growth, we tested the amino acid levels in center and outer leaf
      blades. Younger leaf blades of aposymbiotic plants (no endophyte present) had
      significantly higher levels of asparagine and sometimes glutamine compared to
      older leaf blades. The amino acid levels were much lower in MF-N. siegelii and MF
      N. uncinatum compared to aposymbiotic plants and MF with Epichloe festucae (a
      closely related symbiont), which lacked lolines. We conclude that loline alkaloid
      production in young tissue depleted these amino acid pools and was apparently
      regulated by availability of the amino acid substrates. As a result, lolines
      maximally protect young host tissues in a fashion similar to endogenous plant
      metabolites that conform to optimal defense theory.

PMID- 19403725
TI  - Isolation and characterization of hydroxyproline-rich glycopeptide signals in
      black nightshade leaves.
AB  - A gene encoding a preprohydroxyproline-rich systemin, SnpreproHypSys, was
      identified from the leaves of black nightshade (Solanum nigrum), which is a
      member of a small gene family of at least three genes that have orthologs in
      tobacco (Nicotiana tabacum; NtpreproHypSys), tomato (Solanum lycopersicum;
      SlpreproHypSys), petunia (Petunia hybrida; PhpreproHypSys), potato (Solanum
      tuberosum; PhpreproHypSys), and sweet potato (Ipomoea batatas; IbpreproHypSys).
      SnpreproHypSys was induced by wounding and by treatment with methyl jasmonate.
      The encoded precursor protein contained a signal sequence and was
      posttranslationally modified to produce three hydroxyproline-rich glycopeptide
      signals (HypSys peptides). The three HypSys peptides isolated from nightshade
      leaf extracts were called SnHypSys I (19 amino acids with six pentoses), SnHypSys
      II (20 amino acids with six pentoses), and SnHypSys III (20 amino acids with
      either six or nine pentoses) by their sequential appearance in SnpreproHypSys.
      The three SnHypSys peptides were synthesized and tested for their abilities to
      alkalinize suspension culture medium, with synthetic SnHypSys I demonstrating the
      highest activity. Synthetic SnHypSys I was capable of inducing alkalinization in
      other Solanaceae cell types (or species), indicating that structural
      conformations within the peptides are recognized by the different cells/species
      to initiate signal transduction pathways, apparently through recognition by
      homologous receptor(s). To further demonstrate the biological relevance of the
      SnHypSys peptides, the early defense gene lipoxygenase D was shown to be induced
      by all three synthetic peptides when supplied to excised nightshade plants.

PMID- 19403727
TI  - Two alternatively spliced isoforms of the Arabidopsis SR45 protein have distinct
      roles during normal plant development.
AB  - The serine-arginine-rich (SR) proteins constitute a conserved family of pre-mRNA
      splicing factors. In Arabidopsis (Arabidopsis thaliana), they are encoded by 19
      genes, most of which are themselves alternatively spliced. In the case of SR45,
      the use of alternative 3' splice sites 21 nucleotides apart generates two
      alternatively spliced isoforms. Isoform 1 (SR45.1) has an insertion relative to
      isoform 2 (SR45.2) that replaces a single arginine with eight amino acids
      (TSPQRKTG). The biological implications of SR45 alternative splicing have been
      unclear. A previously described loss-of-function mutant affecting both isoforms,
      sr45-1, shows several developmental defects, including defects in petal
      development and root growth. We found that the SR45 promoter is highly active in
      regions with actively growing and dividing cells. We also tested the ability of
      each SR45 isoform to complement the sr45-1 mutant by overexpression of isoform
      specific green fluorescent protein (GFP) fusion proteins. As expected, transgenic
      plants overexpressing either isoform displayed both nuclear speckles and GFP
      fluorescence throughout the nucleoplasm. We found that SR45.1-GFP complements the
      flower petal phenotype, but not the root growth phenotype. Conversely, SR45.2-GFP
      complements root growth but not floral morphology. Mutation of a predicted
      phosphorylation site within the alternatively spliced segment, SR45.1-S219A-GFP,
      does not affect complementation. However, a double mutation affecting both serine
      219 and the adjacent threonine-218 (SR45.1-T218A + S219A-GFP) behaves like
      isoform 2, complementing the root but not the floral phenotype. In conclusion,
      our study provides evidence that the two alternatively spliced isoforms of SR45
      have distinct biological functions.

PMID- 19403729
TI  - A versatile zero background T-vector system for gene cloning and functional
      genomics.
AB  - With the recent availability of complete genomic sequences of many organisms,
      high-throughput and cost-efficient systems for gene cloning and functional
      analysis are in great demand. Although site-specific recombination-based cloning
      systems, such as Gateway cloning technology, are extremely useful for efficient
      transfer of DNA fragments into multiple destination vectors, the two-step cloning
      process is time consuming and expensive. Here, we report a zero background TA
      cloning system that provides simple and high-efficiency direct cloning of PCR
      amplified DNA fragments with almost no self-ligation. The improved T-vector
      system takes advantage of the restriction enzyme XcmI to generate a T-overhang
      after digestion and the negative selection marker gene ccdB to eliminate the self
      ligation background after transformation. We demonstrate the feasibility and
      flexibility of the technology by developing a set of transient and stable
      transformation vectors for constitutive gene expression, gene silencing, protein
      tagging, protein subcellular localization detection, and promoter fragment
      activity analysis in plants. Because the system can be easily adapted for
      developing specialized expression vectors for other organisms, zero background TA
      provides a general, cost-efficient, and high-throughput platform that complements
      the Gateway cloning system for gene cloning and functional genomics.

PMID- 19403728
TI  - Role of temperature stress on chloroplast biogenesis and protein import in pea.
AB  - Modulation of photosynthesis and chloroplast biogenesis, by low and high
      temperatures, was studied in 12-d-old pea (Pisum sativum) plants grown at 25
      degrees C and subsequently exposed to 7 degrees C or 40 degrees C up to 48 h. The
      decline in variable chlorophyll a fluorescence/maximum chlorophyll a fluorescence
      and estimated electron transport rate in temperature-stressed plants was
      substantially restored when they were transferred to room temperature. The ATP
      driven import of precursor of small subunit of Rubisco (pRSS) into plastids was
      down-regulated by 67% and 49% in heat-stressed and chill-stressed plants,
      respectively. Reduction in binding of the pRSS to the chloroplast envelope
      membranes in heat-stressed plants could be due to the down-regulation of Toc159
      gene/protein expression. In addition to impaired binding, reduced protein import
      into chloroplast in heat-stressed plants was likely due to decreased gene/protein
      expression of certain components of the TOC complex (Toc75), the TIC complex
      (Tic20, Tic32, Tic55, and Tic62), stromal Hsp93, and stromal processing
      peptidase. In chill-stressed plants, the gene/protein expression of most of the
      components of protein import apparatus other than Tic110 and Tic40 were not
      affected, suggesting the central role of Tic110 and Tic40 in inhibition of
      protein import at low temperature. Heating of intact chloroplasts at 35 degrees C
      for 10 min inhibited protein import, implying a low thermal stability of the
      protein import apparatus. Results demonstrate that in addition to decreased gene
      and protein expression, down-regulation of photosynthesis in temperature-stressed
      plants is caused by reduced posttranslational import of plastidic proteins
      required for the replacement of impaired proteins coded by nuclear genome.

PMID- 19403730
TI  - Giant flowers of Southern magnolia are hydrated by the xylem.
AB  - Flowering depends upon long-distance transport to supply water for reproductive
      mechanisms to function. Previous physiological studies suggested that flowers
      operated uncoupled from stem xylem transport and received water primarily from
      the phloem. We demonstrate that the water balance of Southern magnolia (Magnolia
      grandiflora) flowers is regulated in a manner opposite from that of previously
      examined flowers. We show that flowers of Southern magnolia rely upon relatively
      efficient xylem hydraulic transport to support high water demand during anthesis.
      We measured rapid rates of perianth transpiration ranging from twice to 100 times
      greater than previous studies. We found that relatively efficient xylem pathways
      existed between the xylem and flower. Perianth hydraulic conductance and the
      amount of xylem to transpirational surface area ratios of flowers were both
      approximately one-third those measured for leafy shoots. Furthermore, we observed
      that perianth tissues underwent significant diurnal depressions in water status
      during transpiring conditions. Decreases in water potential observed between
      flowers and vegetative tissues were consistent with water moving from the stem
      xylem into the flower during anthesis. Xylem hydraulic coupling of flowers to the
      stem was supported by experiments showing that transpiring flowers were
      unaffected by bark girdling. With Southern magnolia being a member of a nearly
      basal evolutionary lineage, our results suggest that flower water balance
      represents an important functional dimension that influenced early flower
      evolution.

PMID- 19403731
TI  - Sucrose control of translation mediated by an upstream open reading frame-encoded
      peptide.
AB  - Regulation of gene expression through translational control is common in many
      organisms. The Arabidopsis (Arabidopsis thaliana) transcription factor bZIP11 is
      translational repressed in response to sucrose (Suc), resulting in Suc-regulated
      changes in amino acid metabolism. The 5' leader of the bZIP11 mRNA harbors
      several upstream open reading frames (uORFs), of which the second uORF is well
      conserved among bZIP11 homologous genes. The uORF2 element encodes a Suc control
      peptide (SC-peptide) of 28 residues that is sufficient for imposing Suc-induced
      repression of translation (SIRT) on a heterologous mRNA. Detailed analysis of the
      SC-peptide suggests that it functions as an attenuator peptide. Results suggest
      that the SC-peptide inhibits bZIP11 translation in response to high Suc levels by
      stalling the ribosome on the mRNA. The conserved noncanonical AUG contexts of
      bZIP11 uORFs allow inefficient translational initiation of the uORF, resulting in
      translation initiation of the scanning ribosome at the AUG codon of the bZIP11
      main ORF. The results presented show that Suc-dependent signaling mediates
      differential translation of mRNAs containing SC-peptides encoding uORFs.

PMID- 19403732
TI  - The histidine kinase-related domain of Arabidopsis phytochrome a controls the
      spectral sensitivity and the subcellular distribution of the photoreceptor.
AB  - Phytochrome A (phyA) is the primary photoreceptor for sensing extremely low
      amounts of light and for mediating various far-red light-induced responses in
      higher plants. Translocation from the cytosol to the nucleus is an essential step
      in phyA signal transduction. EID1 (for EMPFINDLICHER IM DUNKELROTEN LICHT1) is an
      F-box protein that functions as a negative regulator in far-red light signaling
      downstream of the phyA in Arabidopsis (Arabidopsis thaliana). To identify factors
      involved in EID1-dependent light signal transduction, pools of
      ethylmethylsulfonate-treated eid1-3 seeds were screened for seedlings that
      suppress the hypersensitive phenotype of the mutant. The phenotype of the
      suppressor mutant presented here is caused by a missense mutation in the PHYA
      gene that leads to an amino acid transition in its histidine kinase-related
      domain. The novel phyA-402 allele alters the spectral sensitivity and the
      persistence of far-red light-induced high-irradiance responses. The strong eid1-3
      suppressor phenotype of phyA-402 contrasts with the moderate phenotype observed
      when phyA-402 is introgressed into the wild-type background, which indicates that
      the mutation mainly alters functions in an EID1-dependent signaling cascade. The
      mutation specifically inhibits nuclear accumulation of the photoreceptor molecule
      upon red light irradiation, even though it still interacts with FHY1 (for far-red
      long hypocotyl 1) and FHL (for FHY1-like protein), two factors that are essential
      for nuclear accumulation of phyA. Degradation of the mutated phyA is unaltered
      even under light conditions that inhibit its nuclear accumulation, indicating
      that phyA degradation may occur mostly in the cytoplasm.

PMID- 19403734
TI  - Retrospective analysis of S-1 monotherapy in patients with metastatic colorectal
      cancer after failure to fluoropyrimidine and irinotecan or to fluoropyrimidine,
      irinotecan and oxaliplatin.
AB  - OBJECTIVE: Chemotherapy with irinotecan (CPT-11) or oxaliplatin (l-OHP) in
      combination with infusional 5-fluorouracil (5-FU) and their cross-over as second
      line therapies are standard treatments for metastatic colorectal cancer (MCRC).
      Molecular target agents, which are used as third-line therapies in Western
      countries after failure of these three drugs, have not been available in Japan.
      Monotherapy with S-1 [Tegafur, Oteracil potassium and 5-chloro-2,4
      dihydroxypyrimidine (CDHP)] showed activity against colorectal cancer with a
      response rate of 35% as a first-line therapy. It is not clear whether inhibition
      of dihydropyrimidine dehydrogenase by CDHP can modulate the activity of 5-FU even
      after patients initially fail with 5-FU. This retrospective study evaluated the
      efficacy and safety of monotherapy with S-1 for MCRC after the failure of
      standard chemotherapy. METHODS: The subjects of this study comprised two cohorts;
      the first was 27 patients with MCRC who had failed with 5-FU and CPT-11 before
      approval of l-OHP in Japan (cohort 1), and the second was 23 patients who had
      failed with 5-FU, CPT-11 and l-OHP (cohort 2). S-1 was given orally twice daily
      (80 mg m(2)/day) for 28 days followed by a 14-day rest. RESULTS: In cohorts 1 and
      2, the response rates were 7% and 0%, and the median progression-free survivals
      were 2.8 and 2.7 months, and overall survivals after initiation of S-1 were 10.5
      and 4.7 months, respectively. The common grade 3 and 4 adverse events in cohorts
      1 and 2 were diarrhea 15% and 13%, anorexia 11% and 17% and anemia 26% and 30%,
      respectively. CONCLUSIONS: S-1 monotherapy did not show promising activity
      against MCRC after the failures with 5-FU, CPT-11 and l-OHP.

PMID- 19403735
TI  - Metastatic melanoma on the abdominal wall.

PMID- 19403736
TI  - Comparison of time trends in uterine cancer incidence (1973-2002) in Asia, from
      Cancer Incidence in Five Continents, Vols IV-IX.

PMID- 19403733
TI  - Molecular and biochemical characterization of the parvulin-type PPIases in Lotus
      japonicus.
AB  - The cis/trans isomerization of the peptide bond preceding proline is an
      intrinsically slow process, although important in many biological processes in
      both prokaryotes and eukaryotes. In vivo, this isomerization is catalyzed by
      peptidyl-prolyl cis/trans-isomerases (PPIases). Here, we present the molecular
      and biochemical characterization of parvulin-type PPIase family members of the
      model legume Lotus japonicus, annotated as LjPar1, LjPar2, and LjPar3. Although
      LjPar1 and LjPar2 were found to be homologous to PIN1 (Protein Interacting with
      NIMA)-type parvulins and hPar14 from human, respectively, LjPar3 represents a
      novel multidomain parvulin, apparently present only in plants, that contains an
      active carboxyl-terminal sulfurtransferase domain. All Lotus parvulins were
      heterologously expressed and purified from Escherichia coli, and purified protein
      verification measurements used a liquid chromatography-mass spectrometry-based
      proteomic method. The biochemical characterization of the recombinant Lotus
      parvulins revealed that they possess PPIase activity toward synthetic
      tetrapeptides, although they exhibited different substrate specificities
      depending on the amino acid amino terminal to proline. These differences were
      also studied in a structural context using molecular modeling of the encoded
      polypeptides. Real-time reverse transcription-polymerase chain reaction revealed
      that the three parvulin genes of Lotus are ubiquitously expressed in all plant
      organs. LjPar1 was found to be up-regulated during the later stages of nodule
      development. Subcellular localization of LjPar-enhanced Yellow Fluorescence
      Protein (eYFP) fusions expressed in Arabidopsis (Arabidopsis thaliana) leaf
      epidermal cells revealed that LjPar1- and LjPar2-eYFP fusions were localized in
      the cytoplasm and in the nucleus, in contrast to LjPar3-eYFP, which was clearly
      localized in plastids. Divergent substrate specificities, expression profiles,
      and subcellular localization indicate that plant parvulin-type PPIases are
      probably involved in a wide range of biochemical and physiological processes.

PMID- 19403738
TI  - Promoting science over serendipity in prescribing anti-TNF therapy.

PMID- 19403737
TI  - The ATR-Chk1 pathway plays a role in the generation of centrosome aberrations
      induced by Rad51C dysfunction.
AB  - Rad51C is a central component of two complexes formed by five Rad51 paralogs in
      vertebrates. These complexes are involved in repairing DNA double-strand breaks
      through homologous recombination. Despite accumulating evidence suggesting that
      the paralogs may prevent aneuploidy by controlling centrosome integrity, Rad51C's
      role in maintaining chromosome stability remains unclear. Here we demonstrate
      that Rad51C deficiency leads to both centrosome aberrations in an ATR-Chk1
      dependent manner and increased aneuploidy in human cells. While it was reported
      that Rad51C deficiency did not cause centrosome aberrations in interphase in
      hamster cells, such aberrations were observed in interphase in HCT116 cells with
      Rad51C dysfunction. Caffeine treatment and down-regulation of ATR, but not that
      of ATM, reduced the frequency of centrosome aberrations in the mutant cells.
      Silencing of Rad51C by RNA interference in HT1080 cells resulted in similar
      aberrations. Treatment with a Chk1 inhibitor and silencing of Chk1 also reduced
      the frequency in HCT116 mutants. Accumulation of Chk1 at the centrosome and
      nuclear foci of gamma H2AX were increased in the mutants. Moreover, the mutant
      cells had a higher frequency of aneuploidy. These findings indicate that the ATR
      Chk1 pathway plays a role in increased centrosome aberrations induced by Rad51C
      dysfunction.

PMID- 19403739
TI  - Towards a more inclusive vision of the medical sciences.
AB  - Progress in the medical sciences is largely determined by two things: (i) the
      questions we ask, and (ii) how rigorously and vigorously we attempt to answer
      them. How do we know which questions are the right questions to ask, and thus the
      correct questions to spend our time and energies trying to answer? Such
      evaluative concerns bring into sharper focus the question--'What is medicine
      for?' The international study of rosuvastatin is important not simply because of
      the health benefits it may confer, but because it inspires a more robust and
      inclusive vision of the medical sciences. A vision which recognizes that the
      primary goal of medicine is to promote health, and that includes the health of
      'normal' people as well as those with illness and disease. This inclusive vision
      of the medical sciences is a transformative one, it departs from the 'disease
      model' approach which has dominated distinct areas of medical research for
      decades.

PMID- 19403740
TI  - Visuospatial function is a significant contributor to functional status in
      patients with Alzheimer's disease.
AB  - BACKGROUND: Contribution of visuospatial abilities to the functional status in
      patients with Alzheimer's disease (AD) has been controversial. AIM: To address
      whether visuospatial abilities have independent association with functional
      measures in patients with AD. METHODS: We regressed performances on a global
      cognitive (the revised Hasegawa Dementia Scale: HDSR), executive/
      visuoconstruction (Clock drawing), visuoperception (Clock reading: CRT), simple
      visuoconstruction (figure copying), and frontal behavioral tasks on measures of
      basic and instrumental activities of daily living (BADL and IADL) in 57 patients
      (78.0 + 6.1 years) with AD of various severity (mean HDSR score: 16.0 + 5.9). We
      sought independent contributions of these visuospatial measures to functional
      status. RESULTS: Performance on the CRT contributed significantly to BADL and
      IADL and the results of HDSR contributed to IADL. Results of figure copying
      related significantly to BADL especially in mild AD. CONCLUSION: Visuospatial
      ability is one of the important contributors to functional status.

PMID- 19403741
TI  - Reproducible measurement of human motoneuron excitability with magnetic
      stimulation of the corticospinal tract.
AB  - It is difficult to test responses of human motoneurons in a controlled way or to
      make longitudinal assessments of adaptive changes at the motoneuron level. These
      studies assessed the reliability of responses produced by magnetic stimulation of
      the corticospinal tract. Cervicomedullary motor evoked potentials (CMEPs) were
      recorded in the first dorsal interosseus (FDI) on 2 separate days. On each day,
      four sets of stimuli were delivered at the maximal output of the stimulator, with
      the final two sets>or=10 min after the initial sets. Sets of stimuli were also
      delivered at different stimulus intensities to obtain stimulus-response curves.
      In addition, on the second day, responses at different stimulus intensities were
      evoked during weak voluntary contractions. Responses were normalized to the
      maximal muscle compound action potential (Mmax). CMEPs evoked in the relaxed FDI
      were small, even when stimulus intensity was maximal (3.6+/-2.5% Mmax) but much
      larger during a weak contraction (e.g., 26.2+/-10.2% Mmax). CMEPs evoked in the
      relaxed muscle at the maximal output of the stimulator were highly reproducible
      both within (ICC=0.83, session 1; ICC=0.87, session 2) and between sessions
      (ICC=0.87). ICCs for parameters of the input-output curves, which included
      measures of motor threshold, slope, and maximal response size, ranged between
      0.87 and 0.62. These results suggest that responses to magnetic stimulation of
      the corticospinal tract can be assessed in relaxation and contraction and can be
      reliably obtained for longitudinal studies of motoneuronal excitability.

PMID- 19403744
TI  - Dynamical foundations of the neural circuit for bayesian decision making.
AB  - On the basis of accumulating behavioral and neural evidences, it has recently
      been proposed that the brain neural circuits of humans and animals are equipped
      with several specific properties, which ensure that perceptual decision making
      implemented by the circuits can be nearly optimal in terms of Bayesian inference.
      Here, I introduce the basic ideas of such a proposal and discuss its implications
      from the standpoint of biophysical modeling developed in the framework of
      dynamical systems.

PMID- 19403742
TI  - Temporal features of spectral integration in the inferior colliculus: effects of
      stimulus duration and rise time.
AB  - This report examines temporal features of facilitation and suppression that
      underlie spectrally integrative responses to complex vocal signals. Auditory
      responses were recorded from 160 neurons in the inferior colliculus (IC) of awake
      mustached bats. Sixty-two neurons showed combination-sensitive facilitation:
      responses to best frequency (BF) signals were facilitated by well-timed signals
      at least an octave lower in frequency, in the range 16-31 kHz. Temporal features
      and strength of facilitation were generally unaffected by changes in duration of
      facilitating signals from 4 to 31 ms. Changes in stimulus rise time from 0.5 to
      5.0 ms had little effect on facilitatory strength. These results suggest that low
      frequency facilitating inputs to high BF neurons have phasic-on temporal patterns
      and are responsive to stimulus rise times over the tested range. We also recorded
      from 98 neurons showing low-frequency (11-32 kHz) suppression of higher BF
      responses. Effects of changing duration were related to the frequency of
      suppressive signals. Signals<23 kHz usually evoked suppression sustained
      throughout signal duration. This and other features of such suppression are
      consistent with a cochlear origin that results in masking of responses to higher,
      near-BF signal frequencies. Signals in the 23- to 30-kHz range-frequencies in the
      first sonar harmonic-generally evoked phasic suppression of BF responses. This
      may result from neural inhibitory interactions within and below IC. In many
      neurons, we observed two or more forms of the spectral interactions described
      here. Thus IC neurons display temporally and spectrally complex responses to
      sound that result from multiple spectral interactions at different levels of the
      ascending auditory pathway.

PMID- 19403743
TI  - Influence of subcortical inhibition on barrel cortex receptive fields.
AB  - Influence of subcortical inhibition on barrel cortex receptive fields. By the
      time neural responses driven by vibrissa stimuli reach the barrel cortex, they
      have undergone significant spatial and temporal transformations within
      subcortical relays. A major regulator of these transformations is thought to be
      subcortical GABA-mediated inhibition, but the actual degree of this influence is
      unknown. We used disinhibition produced by GABA receptor antagonists to unmask
      the excitatory sensory responses that are normally suppressed by inhibition in
      the main subcortical sensory relays to barrel cortex; principal trigeminal (Pr5)
      and primary thalamic (VPM) nuclei. We found that, within subcortical relays,
      inhibition only slightly suppresses short-latency receptive field responses, but
      robustly suppresses long-latency center and surround receptive field responses.
      However, the long-latency subcortical effects of inhibition are mostly not
      reflected in the barrel cortex. The most robust effect of subcortical inhibition
      on barrel cortex responses is to transiently suppress the receptive field
      responses of high-frequency sensory stimuli. This transient adaptation caused by
      subcortical inhibition recovers within a few stimuli and gives way to a steady
      state adaptation that is independent of subcortical inhibition.

PMID- 19403745
TI  - Touching sounds: thalamocortical plasticity and the neural basis of multisensory
      integration.
AB  - To date, noninvasive neuroimaging research on multisensory perception has focused
      on cortical activations. In a series of elegant functional magnetic resonance
      imaging experiments, Beauchamp and Ro recently investigated altered cortical
      activations associated with acquired sound-touch synesthesia resulting from a
      thalamic lesion. Their findings highlight the important role of intact
      thalamocortical projections for preventing illusory crossmodal perception and for
      underlying reliable multisensory integration.

PMID- 19403746
TI  - Dynamic characterization of agonist and antagonist oculomotoneurons during
      conjugate and disconjugate eye movements.
AB  - In this report, we provide the first quantitative characterization of the
      relationship between the spike train dynamics of medial rectus oculomotoneurons
      (OMNs) and eye movements during conjugate and disconjugate saccades. We show that
      a simple, first-order model (i.e., containing eye position and velocity terms)
      provided an adequate model of neural discharges during both on and off-directed
      conjugate saccades, while a second-order model, which included a decaying slide
      term, significantly improved the ability to fit neuronal responses by
      approximately 10% (P<0.05). To understand how the same neurons drove disconjugate
      eye movements, we evaluated whether sensitivities estimated during conjugate
      saccades could be used to predict responses during disconjugate saccades. For the
      majority of neurons (68%), a conjugate-based model failed, and instead neurons
      preferentially encoded the position and velocity of the ipsilateral eye. Similar
      to our previous results with abducens motoneurons, we also found that position
      and velocity sensitivities of OMNs decreased with increasing velocity, and the
      simulated population drive of OMNs during disconjugate saccades was less
      (approximately 10%) than during conjugate saccades. Taken together, our results
      provide evidence that the activation of the antagonist, as well as agonist,
      motoneuron pools must be considered to understand the neural control of
      horizontal eye movements across different oculomotor behaviors. Moreover, we
      propose that the undersampling of smaller motoneurons (e.g., nontwitch) was
      likely to account for the missing drive observed during disconjugate saccades;
      these cells are thought to be more specialized for vergence movements and thus
      could provide the additional input required to command disconjugate eye
      movements.

PMID- 19403747
TI  - Two interacting olfactory transduction mechanisms have linked polarities and
      dynamics in Drosophila melanogaster antennal basiconic sensilla neurons.
AB  - We measured frequency response functions between concentrations of fruit odorants
      and individual action potentials in large basiconic sensilla of the Drosophila
      melanogaster antenna. A new method of randomly varying odorant concentration was
      combined with rapid, continuous measurement of concentration at the antenna by a
      miniature photoionization detector. All frequency responses decreased
      progressively at frequencies approaching 100 Hz, providing an upper limit for the
      dynamics of Drosophila olfaction. We found two distinct response patterns:
      excitatory band-pass frequency responses were seen with ethyl acetate, ethyl
      butyrate, and hexanol, whereas inhibitory low-pass responses were seen with
      methyl salicylate and phenylethyl acetate. Band-pass responses peaked at 1-10 Hz.
      Frequency responses could be well fitted by simple linear filter equations, and
      the fitted parameters were consistent within each of the two types of responses.
      Experiments with equal mixtures of excitatory and inhibitory odorants gave
      responses that were characteristic of the inhibitory components, indicating that
      interaction during transduction causes inhibitory odorants to suppress the
      responses to excitatory odorants. Plots of response amplitude versus odorant
      concentration indicated that the odorant concentrations used were within
      approximately linear regions of the dose response relationships. We also
      estimated linear information capacity from the coherence function of each
      recording. Although coherence was relatively high, indicating a large signal-to
      noise ratio, information capacity for olfaction was much lower than comparable
      estimates for mechanotransduction or visual transduction because of the limited
      bandwidth of olfaction. These data offer new insights into transduction by
      primary chemoreceptors and place temporal constraints on Drosophila olfactory
      behavior.

PMID- 19403748
TI  - Zona incerta: a role in central pain.
AB  - Central pain syndrome (CPS) is a debilitating condition that affects a large
      number of patients with a primary lesion or dysfunction in the CNS. Despite its
      discovery over a century ago, the pathophysiological processes underlying the
      development and maintenance of CPS are poorly understood. We recently
      demonstrated that activity in the posterior thalamus (PO) is tightly regulated by
      inhibitory inputs from zona incerta (ZI). Here we test the hypothesis that CPS is
      associated with abnormal inhibitory regulation of PO by ZI. We recorded single
      units from ZI and PO in animals with CPS resulting from spinal cord lesions.
      Consistent with our hypothesis, the spontaneous firing rate and somatosensory
      evoked responses of ZI neurons were lower in lesioned animals compared with sham
      operated controls. In PO, neurons recorded from lesioned rats exhibited
      significantly higher spontaneous firing rates and greater responses to noxious
      and innocuous stimuli applied to the hindpaw and to the face. These changes were
      not associated with increased afferent drive from the spinal trigeminal nucleus
      or changes in the ventroposterior thalamus. Thus CPS can result from suppressed
      inputs from the inhibitory nucleus zona incerta to the posterior thalamus.

PMID- 19403749
TI  - Extrasynaptic release of GABA by retinal dopaminergic neurons.
AB  - GABA release by dopaminergic amacrine (DA) cells of the mouse retina was detected
      by measuring Cl- currents generated by isolated perikarya in response to their
      own neurotransmitter. The possibility that the Cl- currents were caused by GABA
      release from synaptic endings that had survived the dissociation of the retina
      was ruled out by examining confocal Z series of the surface of dissociated
      tyrosine hydroxylase-positive perikarya after staining with antibodies to pre and
      postsynaptic markers. GABA release was caused by exocytosis because 1) the
      current events were transient on the millisecond time scale and thus resembled
      miniature synaptic currents; 2) they were abolished by treatment with a blocker
      of the vesicular proton pump, bafilomycin A1; and 3) their frequency was
      controlled by the intracellular Ca2+ concentration. Because DA cell perikarya do
      not contain presynaptic active zones, release was by necessity extrasynaptic. A
      range of depolarizing stimuli caused GABA exocytosis, showing that extrasynaptic
      release of GABA is controlled by DA cell electrical activity. With all modalities
      of stimulation, including long-lasting square pulses, segments of pacemaker
      activity delivered by the action-potential-clamp method and high-frequency trains
      of ramps, discharge of GABAergic currents exhibited considerable variability in
      latency and duration, suggesting that coupling between Ca2+ influx and
      transmitter exocytosis is extremely loose in comparison with the synapse.
      Paracrine signaling based on extrasynaptic release of GABA by DA cells and other
      GABAergic amacrines may participate in controlling the excitability of the
      neuronal processes that interact synaptically in the inner plexiform layer.

PMID- 19403750
TI  - Impact of persistent cortical activity (up States) on intracortical and
      thalamocortical synaptic inputs.
AB  - The neocortex generates short epochs of persistent activity called up states,
      which are associated with changes in cellular and network excitability. Using
      somatosensory thalamocortical slices, we studied the impact of persistent
      cortical activity during spontaneous up states on intrinsic cellular excitability
      (input resistance) and on excitatory synaptic inputs of cortical cells. At the
      intrinsic excitability level, we found that the expected decrease in input
      resistance (high conductance) resulting from synaptic barrages during up states
      is counteracted by an increase in input resistance due to depolarization per se.
      The result is a variable but on average relatively small reduction in input
      resistance during up states. At the synaptic level, up states enhanced a late
      synaptic component of short-latency thalamocortical field potential responses but
      suppressed intracortical field potential responses. The thalamocortical
      enhancement did not reflect an increase in synaptic strength, as determined by
      measuring the evoked postsynaptic current, but instead an increase in evoked
      action potential (spike) probability due to depolarization during up states. In
      contrast, the intracortical suppression was associated with a reduction in
      synaptic strength, apparently driven by increased presynaptic intracortical
      activity during up states. In addition, intracortical suppression also reflected
      a reduction in evoked spike latency caused by depolarization and the abolishment
      of longer-latency spikes caused by stronger inhibitory drive during up states. In
      conclusion, depolarization during up states increases the success of excitatory
      synaptic inputs to reach firing. However, activity-dependent synaptic depression
      caused by increased presynaptic firing during up states and the enhancement of
      evoked inhibitory drive caused by depolarization suppress excitatory
      intracortical synaptic inputs.

PMID- 19403751
TI  - Contribution of sensorimotor integration to spinal stabilization in humans.
AB  - The control of upper body (UB) orientation relative to the pelvis in the frontal
      plane was characterized by analyzing responses to external perturbations
      consisting of continuous pelvis tilts (eyes open [EO] and eyes closed [EC]) and
      visual surround tilts (EO) at various amplitudes. Lateral sway of the lower body
      was prevented on all tests. UB sway was analyzed by calculating impulse-response
      functions (IRFs) and frequency-response functions (FRFs) from 0.023 to 10.3 Hz
      for pelvis tilt tests and FRFs from 0.041 to 1.5 Hz for visual tests. For pelvis
      tilt tests, differences between FRFs were limited to frequencies<3 Hz and were
      dependent on stimulus amplitude. IRFs were nearly identical across all pelvis
      tilt tests for the first 0.2 s, but showed amplitude-dependent changes in their
      time course at longer time lags. The availability of visual orientation cues (EO
      vs. EC) had only a small effect on the UB sway during pelvis tilt tests. This
      small effect of vision was consistent with the small UB sway evoked on visual
      tilt tests. Experimental results were interpreted using a feedback model of UB
      orientation control that included time-delayed sensory integration, short-latency
      reflexive mechanisms, and intrinsic biomechanical properties of the UB. Variation
      in model parameters indicated that subjects shifted toward reliance on vestibular
      information and away from proprioceptive information as pelvis tilt amplitudes
      increased. For visual tilt stimuli, model parameters indicated that subjects
      shifted toward reliance on vestibular and proprioceptive information and away
      from visual information as the stimulus amplitude increased.

PMID- 19403752
TI  - Signaling of grasp dimension and grasp force in dorsal premotor cortex and
      primary motor cortex neurons during reach to grasp in the monkey.
AB  - A fundamental question is how the CNS controls the hand with its many degrees of
      freedom. Several motor cortical areas, including the dorsal premotor cortex (PMd)
      and primary motor cortex (M1), are involved in reach to grasp. Although neurons
      in PMd are known to modulate in relation to the type of grasp and neurons in M1
      in relation to grasp force and finger movements, whether specific parameters of
      whole hand shaping are encoded in the discharge of these cells has not been
      studied. In this study, two monkeys were trained to reach and grasp 16 objects
      varying in shape, size, and orientation. Grasp force was explicitly controlled,
      requiring the monkeys to exert either three or five levels of grasp force on each
      object. The animals were unable to see the objects or their hands. Single PMd and
      M1 neurons were recorded during the task, and cell firing was examined for
      modulation with object properties and grasp force. The firing of the vast
      majority of PMd and M1 neurons varied significantly as a function of the object
      presented as well as the object grasp dimension. Grasp dimension of the object
      was an important determinant of the firing of cells in both PMd and M1. A smaller
      percentage of PMd and M1 neurons were modulated by grasp force. Linear encoding
      was prominent with grasp force but less so with grasp dimension. The correlations
      with grasp dimension and grasp force were stronger in the firing of M1 than PMd
      neurons and across both regions the modulation with these parameters increased as
      reach to grasp proceeded. All PMd and M1 neurons that signaled grasp force also
      signaled grasp dimension, yet the two signals showed limited interactions,
      providing a neural substrate for the independent control of these two parameters
      at the behavioral level.

PMID- 19403753
TI  - The polyadenylation site of Mimivirus transcripts obeys a stringent 'hairpin
      rule'.
AB  - Mimivirus, a giant DNA virus infecting Acanthamoeba, is revealing an increasing
      list of unique features such as a 1.2-Mb genome with numerous genes not found in
      other viruses, a uniquely conserved promoter signal, and a particle of unmatched
      complexity using two distinct portals for genome delivery and packaging. Herein,
      we contribute a further Mimivirus distinctive feature discovered by sequencing a
      panel of viral cDNAs produced for probing the structure of Mimivirus transcripts.
      All Mimivirus mRNAs are polyadenylated at a site coinciding exactly with
      unrelated, but strongly palindromic, genomic sequences. The analysis of 454 Life
      Sciences (Roche) FLX cDNA tags (150,651) confirmed this finding for all Mimivirus
      genes independent of their transcription timings and expression levels. The
      absence of a suitable palindromic signal between adjacent genes results in
      transcripts encompassing multiple ORFs in the same or even in opposite
      orientations. Surprisingly, Mimivirus tRNAs are expressed as polyadenylated
      messengers, including an ORF/tRNA composite mRNA. To our knowledge, both the
      nature and the stringency of the "hairpin rule" defining the location of
      polyadenylation sites are unique, raising once more the question of Mimivirus's
      evolutionary origin. The precise molecular mechanisms implementing the hairpin
      rule into the 3'-end processing of Mimivirus pre-mRNAs remain to be elucidated.

PMID- 19403755
TI  - Comparison of poliovirus recombinants: accumulation of point mutations provides
      further advantages.
AB  - The roles of recombination and accumulation of point mutations in the origin of
      new poliovirus (PV) characteristics have been hypothesized, but it is not known
      which are essential to evolution. We studied phenotypic differences between
      recombinant PV strains isolated from successive stool specimens of an oral PV
      vaccine recipient. The studied strains included three PV2/PV1 recombinants with
      increasing numbers of mutations in the VP1 gene, two of the three with an amino
      acid change I-->T in the DE-loop of VP1, their putative PV1 parent and strains
      Sabin 1 and 2. Growth of these viruses was examined in three cell lines:
      colorectal adenocarcinoma, neuroblastoma and HeLa. The main observation was a
      higher growth rate between 4 and 6 h post-infection of the two recombinants with
      the I-->T substitution. All recombinants grew at a higher rate than parental
      strains in the exponential phase of the replication cycle. In a temperature
      sensitivity test, the I-->T-substituted recombinants replicated equally well at
      an elevated temperature. Complete genome sequencing of the three recombinants
      revealed 12 (3), 19 (3) and 27 (3) nucleotide (amino acid) differences from
      Sabin. Mutations were located in regions defining attenuation, temperature
      sensitivity, antigenicity and the cis-acting replicating element. The
      recombination site was in the 5' end of 3D. In a competition assay, the most
      mutated recombinant beat parental Sabin in all three cell lines, strongly
      suggesting that this virus has an advantage. Two independent intertypic
      recombinants, PV3/PV1 and PV3/PV2, also showed similar growth advantages, but
      they also contained several point mutations. Thus, our data defend the hypothesis
      that accumulation of certain advantageous mutations plays a key role in gaining
      increased fitness.

PMID- 19403754
TI  - Virulence variation among isolates of western equine encephalitis virus in an
      outbred mouse model.
AB  - Little is known about viral determinants of virulence associated with western
      equine encephalitis virus (WEEV). Here, we have analysed six North American WEEV
      isolates in an outbred CD1 mouse model. Full genome sequence analyses showed < or
      =2.7 % divergence among the six WEEV isolates. However, the percentage mortality
      and mean time to death (MTD) varied significantly when mice received subcutaneous
      injections of 10(3) p.f.u. of each virus. Two WEEV strains, McMillan (McM) and
      Imperial 181 (IMP), were the most divergent of the six in genome sequence; McM
      caused 100 % mortality by 5 days post-infection, whereas IMP caused no mortality.
      McM had significantly higher titres in the brain than IMP. Similar differences in
      virulence were observed when McM and IMP were administered by aerosol, intranasal
      or intravenous routes. McM was 100 % lethal with an MTD of 1.9 days when 10(3)
      p.f.u. of each virus was administered by intracerebral inoculation; in contrast,
      IMP caused no mortality. The presence of IMP in the brains after infection by
      different routes and the lack of observed mortality confirmed that IMP is
      neuroinvasive but not neurovirulent. Based on morbidity, mortality, MTD, severity
      of brain lesions, virus distribution patterns, routes of infection and
      differences in infection of cultured cells, McM and IMP were identified as high-
      and low-virulence isolates, respectively.

PMID- 19403756
TI  - Effect of citrus hosts on the generation, maintenance and evolutionary fate of
      genetic variability of citrus exocortis viroid.
AB  - Citrus exocortis viroid (CEVd) populations are composed of closely related
      haplotypes whose frequencies in the population result from the equilibrium
      between mutation, selection and genetic drift. The genetic diversity of CEVd
      populations infecting different citrus hosts was studied by comparing populations
      recovered from infected trifoliate orange and sour orange seedling trees after 10
      years of evolution, with the ancestral population maintained for the same period
      in the original host, Etrog citron. Furthermore, populations isolated from these
      trifoliate orange and sour orange trees were transmitted back to Etrog citron
      plants and the evolution of their mutant spectra was studied. The results
      indicate that (i) the amount and composition of the within-plant genetic
      diversity generated varies between these two hosts and is markedly different from
      that which is characteristic of the original Etrog citron host and (ii) the
      genetic diversity found after transmitting back to Etrog citron is
      indistinguishable from that which is characteristic of the ancestral Etrog citron
      population, regardless of the citrus plant from which the evolved populations
      were isolated. The relationship between the CEVd populations from Etrog citron
      and trifoliate orange, both sensitive hosts, and those from sour orange, which is
      a tolerant host, is discussed.

PMID- 19403757
TI  - A mutation in helicase motif IV of herpes simplex virus type 1 UL5 that results
      in reduced growth in vitro and lower virulence in a murine infection model is
      related to the predicted helicase structure.
AB  - A variant was selected from a clinical isolate of herpes simplex virus type 1
      (HSV-1) during a single passage in the presence of a helicase-primase inhibitor
      (HPI) at eight times the IC(50). The variant was approximately 40-fold resistant
      to the HPI BAY 57-1293 and it showed significantly reduced growth in tissue
      culture with a concomitant reduction in virulence in a murine infection model.
      The variant contained a single mutation (Asn342Lys) in the UL5 predicted
      functional helicase motif IV. The Asn342Lys mutation was transferred to a
      laboratory strain, PDK cl-1, and the recombinant acquired the expected resistance
      and reduced growth characteristics. Comparative modelling and docking studies
      predicted the Asn342 position to be physically distant from the HPI interaction
      pocket formed by UL5 and UL52 (primase). We suggest that this mutation results in
      steric/allosteric modification of the HPI-binding pocket, conferring an indirect
      resistance to the HPI. Slower growth and moderately reduced virulence suggest
      that this mutation might also interfere with the helicase-primase activity.

PMID- 19403759
TI  - Identification of Streptococcus agalactiae isolates from various phylogenetic
      lineages by matrix-assisted laser desorption ionization-time of flight mass
      spectrometry.
AB  - Variations in proteins related to bacterial diversity may affect species
      identification performed using matrix-assisted laser desorption ionization
      (MALDI)-time of flight mass spectrometry. Using this method, we identified 110
      Streptococcus agalactiae isolates characterized by serotyping and multilocus
      sequence typing. Serotype III and sequence type 23 strains expressed the widest
      variation in molecular weight of putative "species-identifying" biomarker ions.
      Recognition of the diversity of MALDI patterns observed in strains that represent
      all major intraspecies lineages assists in the constitution of an optimal
      reference database.

PMID- 19403758
TI  - Rapid real-time nucleic Acid sequence-based amplification-molecular beacon
      platform to detect fungal and bacterial bloodstream infections.
AB  - Bloodstream infections (BSIs) are a significant cause of morbidity and mortality.
      Successful patient outcomes are diminished by a failure to rapidly diagnose these
      infections and initiate appropriate therapy. A rapid and reliable diagnostic
      platform of high sensitivity is needed for the management of patients with BSIs.
      The combination of an RNA-dependent nucleic acid sequence-based amplification and
      molecular beacon (NASBA-MB) detection system in multiplex format was developed to
      rapidly detect medically important BSI organisms. Probes and primers representing
      pan-gram-negative, pan-gram-positive, pan-fungal, pan-Candida, and pan
      Aspergillus organisms were established utilizing 16S and 28S rRNA targets for
      bacteria and fungi, respectively. Two multiplex panels were developed to rapidly
      discriminate bacterial or fungal infections at the subkingdom/genus level with a
      sensitivity of 1 to 50 genomes. A clinical study was performed to evaluate the
      accuracy of this platform by evaluating 570 clinical samples from a tertiary-care
      hospital group using blood bottle samples. The sensitivity, specificity, and
      Youden's index values for pan-gram-positive detection and pan-gram-negative
      detection were 99.7%, 100%, 0.997 and 98.6%, 95.9%, 0.945, respectively. The
      positive predictive values (PPV) and the negative predictive values (NPV) for
      these two probes were 100, 90.7, and 99.4, 99.4, respectively. Pan-fungal and pan
      Candida probes showed 100% sensitivity, specificity, PPV, and NPV, and the pan
      Aspergillus probe showed 100% NPV. Robust signals were observed for all probes in
      the multiplex panels, with signal detection in <15 min. The multiplex real-time
      NASBA-MB assay provides a valuable platform for the rapid and specific diagnosis
      of bloodstream pathogens, and reliable pathogen identification and
      characterization can be obtained in under 3 h.

PMID- 19403760
TI  - Reverse transcription-loop-mediated isothermal amplification assay for rapid
      detection of hepatitis E virus.
AB  - The one-step single-tube betaine-free reverse transcription (RT)-loop-mediated
      isothermal amplification assay was developed for rapid diagnosis of hepatitis E
      virus. This assay amplified the target gene in less than 45 min (even as short as
      20 min) under isothermal conditions at 63 degrees C, and the sensitivity of this
      assay was 100-fold greater than that of RT-PCR. This assay demonstrated a
      detection limit of 0.045 fg (nine copies/reaction).

PMID- 19403761
TI  - Evaluation of five commercial real-time PCR assays for detection of Mycoplasma
      pneumoniae in respiratory tract specimens.
AB  - The performances of five commercial TaqMan real-time PCR assays for the detection
      of Mycoplasma pneumoniae in respiratory tract specimens were evaluated in
      comparison with an in-house real-time PCR. All kits allowed prompt and specific
      results, validated by the use of an internal control. The Nanogen kit showed the
      best clinical sensitivity.

PMID- 19403763
TI  - Pyrosequencing analysis of 20 nucleotides of internal transcribed spacer 2
      discriminates Candida parapsilosis, Candida metapsilosis, and Candida
      orthopsilosis.
AB  - Two new cryptic sister species, Candida orthopsilosis and Candida metapsilosis,
      were recently identified by consistent DNA sequence differences among several
      genes within the genetically heterogeneous Candida parapsilosis complex. Here, we
      present data demonstrating that Pyrosequencing analysis of 20 nucleotides of
      internal transcribed spacer region 2 rapidly and robustly distinguishes between
      these three closely related Candida species.

PMID- 19403762
TI  - RNA (E6 and E7) assays versus DNA (E6 and E7) assays for risk evaluation for
      women infected with human papillomavirus.
AB  - In the majority of cases, high-risk human papillomavirus (HR HPV) infections
      regress spontaneously, with only a small percentage progressing to high-grade
      lesions. Current screening methods are based on DNA detection. An alternative
      would be to monitor expression of the E6 and E7 viral oncogenes continuously
      expressed by malignant phenotypes. In the work reported in this paper, we
      compared the two methods for a group of women with high-risk HPV infections.
      Cervical specimens from 400 women, previously found to be HPV DNA positive, were
      analyzed for HPV DNA by a liquid hybridization assay and typed by multiplex PCR
      (for types 16, 18, 31, and 33). Identification of HR HPV E6 and E7 RNA
      transcripts was performed using real-time reverse transcription-PCR and nucleic
      acid sequence-based amplification assays. Results were compared with concurrent
      cytological data. HR HPVs were found in 61.2% of patients. The most common
      genotype was HPV type 16 (HPV-16) (47.1%), followed by HPV-18, HPV-31, and HPV
      33. Nine percent of cases involved other genotypes. Among 223 HPV DNA-positive
      samples, only 118 were positive in the RNA test. Among HPV DNA-positive patients
      with normal cytology, we detected E6 and E7 RNA transcripts in two cases (18.2%).
      The rate of detection increased gradually with the grade of the observed lesions,
      rising from 20% for patients with atypical squamous cells of undetermined
      significance to 48.1% for women with low-grade squamous intraepithelial lesions
      and 86.3% for those with high-grade squamous intraepithelial lesions. These
      results suggest that testing for HPV E6 and E7 transcripts could be a useful tool
      for screening and patient management, providing more accurate predictions of risk
      than those obtained by DNA testing.

PMID- 19403764
TI  - The first vancomycin-intermediate Staphylococcus aureus strains isolated from
      patients in Thailand.
AB  - We screened 533 and 361 methicillin (meticillin)-resistant Staphylococcus aureus
      strains isolated in a university hospital in 2002 and 2003 and in 2006 and 2007,
      respectively, and identified 4 (0.8%) of the strains in the first group and 8
      (2.2%) of the strains in second group as heterogeneous vancomycin-resistant S.
      aureus (heterogeneous VISA) strains and 3 (0.8%) of the strains in the second
      group as VISA strains. This is the first report of VISA strains isolated from
      patients in Thailand.

PMID- 19403765
TI  - Epidemic of postsurgical infections caused by Mycobacterium massiliense.
AB  - An epidemic of infections after video-assisted surgery (1,051 possible cases)
      caused by rapidly growing mycobacteria (RGM) and involving 63 hospitals in the
      state of Rio de Janeiro, Brazil, occurred between August 2006 and July 2007. One
      hundred ninety-seven cases were confirmed by positive acid-fast staining and/or
      culture techniques. Thirty-eight hospitals had cases confirmed by mycobacterial
      culture, with a total of 148 available isolates recovered from 146 patients. Most
      (n = 144; 97.2%) isolates presented a PRA-hsp65 restriction pattern suggestive of
      Mycobacterium bolletii or Mycobacterium massiliense. Seventy-four of these
      isolates were further identified by hsp65 or rpoB partial sequencing, confirming
      the species identification as M. massiliense. Epidemic isolates showed
      susceptibility to amikacin (MIC at which 90% of the tested isolates are inhibited
      [MIC(90)], 8 microg/ml) and clarithromycin (MIC(90), 0.25 microg/ml) but
      resistance to ciprofloxacin (MIC(90), >or=32 microg/ml), cefoxitin (MIC(90), 128
      microg/ml), and doxycycline (MIC(90), >or=64 microg/ml). Representative epidemic
      M. massiliense isolates that were randomly selected, including at least one
      isolate from each hospital where confirmed cases were detected, belonged to a
      single clone, as indicated by the analysis of pulsed-field gel electrophoresis
      (PFGE) patterns. They also had the same PFGE pattern as that previously observed
      in two outbreaks that occurred in other Brazilian cities; we designated this
      clone BRA100. All five BRA100 M. massiliense isolates tested presented consistent
      tolerance to 2% glutaraldehyde. This is the largest epidemic of postsurgical
      infections caused by RGM reported in the literature to date in Brazil.

PMID- 19403766
TI  - Aspergillus section Fumigati typing by PCR-restriction fragment polymorphism.
AB  - Recent studies have shown that there are multiple clinically important members of
      the Aspergillus section Fumigati that are difficult to distinguish on the basis
      of morphological features (e.g., Aspergillus fumigatus, A. lentulus, and
      Neosartorya udagawae). Identification of these organisms may be clinically
      important, as some species vary in their susceptibilities to antifungal agents.
      In a prior study, we utilized multilocus sequence typing to describe A. lentulus
      as a species distinct from A. fumigatus. The sequence data show that the gene
      encoding beta-tubulin, benA, has high interspecies variability at intronic
      regions but is conserved among isolates of the same species. These data were used
      to develop a PCR-restriction fragment length polymorphism (PCR-RFLP) method that
      rapidly and accurately distinguishes A. fumigatus, A. lentulus, and N. udagawae,
      three major species within the section Fumigati that have previously been
      implicated in disease. Digestion of the benA amplicon with BccI generated unique
      banding patterns; the results were validated by screening a collection of
      clinical strains and by in silico analysis of the benA sequences of Aspergillus
      spp. deposited in the GenBank database. PCR-RFLP of benA is a simple method for
      the identification of clinically important, similar morphotypes of Aspergillus
      spp. within the section Fumigati.

PMID- 19403767
TI  - Putative adhesins of enteropathogenic and enterohemorrhagic Escherichia coli of
      serogroup O26 isolated from humans and cattle.
AB  - Enterohemorrhagic Escherichia coli (EHEC) strains are responsible for food
      poisoning in developed countries via consumption of vegetal and animal food
      sources contaminated by ruminant feces, and some strains (O26, O111, and O118
      serogroups) are also responsible for diarrhea in young calves. The prevalence of
      27 putative adhesins of EHEC and of bovine necrotoxigenic E. coli (NTEC) was
      studied with a collection of 43 bovine and 29 human enteropathogenic (EPEC) and
      EHEC strains and 5 non-EPEC/non-EHEC (1 bovine and 4 human) O26 strains, using
      specific PCRs. Four "groups" of adhesins exist, including adhesins present in all
      O26 strains, adhesins present in most O26 strains, adhesins present in a few O26
      strains, and adhesins not present in O26 strains. The common profile of EHEC/EPEC
      strains was characterized by the presence of loc3, loc5, loc7, loc11, loc14, paa,
      efa1, iha, lpfA(O26), and lpfA(O113) genes and the absence of loc1, loc2, loc6,
      loc12, loc13, saa, and eibG genes. Except for the lpfA(O26) gene, which was
      marginally associated with bovine EHEC/EPEC strains in comparison with human
      strains (P = 0.012), none of the results significantly differentiated bovine
      strains from human strains. One adhesin gene (ldaE) was statistically (P < 0.01)
      associated with O26 EHEC/EPEC strains isolated from diarrheic calves in
      comparison with strains isolated from healthy calves. ldaE-positive strains could
      therefore represent a subgroup possessing the specific property of producing
      diarrhea in young calves. This is the first time that the distribution of
      putative adhesins has been described for such a large collection of EHEC/EPEC O26
      strains isolated from both humans and cattle.

PMID- 19403768
TI  - Comparison of a variable-number tandem-repeat (VNTR) method for typing
      Mycobacterium avium with mycobacterial interspersed repetitive-unit-VNTR and
      IS1245 restriction fragment length polymorphism typing.
AB  - Mycobacterium avium complex (MAC) infections are increasing annually in various
      countries, including Japan, but the route of transmission and pathophysiology of
      the infection remain unclear. Currently, a variable-number tandem-repeat (VNTR)
      typing method using the Mycobacterium avium tandem repeat (MATR) loci (MATR-VNTR)
      is employed in Japan for epidemiological studies using clinical isolates of M.
      avium. In this study, the usefulness of this MATR-VNTR typing method was compared
      with that of the IS1245-restriction fragment length polymorphism (IS1245-RFLP)
      typing method and a mycobacterial interspersed repetitive-unit (MIRU)-VNTR typing
      method reported previously (V. C. Thibault, M. Grayon, M. L. Boschiroli, C.
      Hubbans, P. Overduin, K. Stevenson, M. C. Gutierrez, P. Supply, and F. Biet, J.
      Clin. Microbiol. 45:2404-2410, 2007). Seventy clinical isolates identified as M.
      avium from human immunodeficiency virus-negative patients with MAC infections
      were used. MATR-VNTR typing using 15 loci distinguished 56 patterns of different
      allele profiles, yielding a Hunter-Gaston discriminatory index (HGDI) of 0.990.
      However, IS1245-RFLP and MIRU-VNTR typing yielded HGDIs of 0.960 and 0.949,
      respectively, indicating that MATR-VNTR has an excellent discriminatory power
      compared with MIRU-VNTR and IS1245-RFLP typing. Moreover, concomitant use of the
      MATR-VNTR method and IS1245-RFLP typing increased the HGDI to 0.999. MATR-VNTR
      typing is inexpensive and easy to perform and could thus be useful in
      establishing a digital multifacility database that will greatly contribute to the
      clarification of the transmission route and pathophysiology of M. avium
      infections.

PMID- 19403769
TI  - Vancomycin MICs for Staphylococcus aureus vary by detection method and have
      subtly increased in a pediatric population since 2005.
AB  - Vancomycin MICs for Staphylococcus aureus isolates in a pediatric hospital with a
      high rate of staphylococcal infections were examined for any increase over a 7
      year period. A broth microdilution scheme allowed direct comparison of the MICs
      generated by this method to MICs generated by Etest. MICs generated by both
      methods were determined with the same inoculum suspension. One hundred sixty-five
      S. aureus isolates were selected on the basis of the patients having been
      bacteremic or having received vancomycin as the definitive therapy for their
      infections. Of the 165 isolates, 117 were methicillin-resistant S. aureus and 48
      were methicillin-susceptible S. aureus. Forty-seven were acquired in the hospital
      (nosocomial), 56 were community acquired, and 62 were community onset-health care
      associated. All but one isolate tested by broth microdilution had MICs of < 1.0
      microg/ml, while 96% of these same isolates tested by Etest had MICs of > or = 1
      microg/ml. A significant increase in MICs that occurred after study year 4 (2004
      to 2005) was demonstrated by the Etest (P < 0.00007) but not by broth
      microdilution. MICs were not different for isolates of community or health care
      origin, regardless of methodology. The proportion of isolates with Etest MICs of
      < 1 and > or = 1 microg/ml between children with bacteremia for < or = 5 days and
      > 5 days (P = 0.3) was not different. We conclude that MICs for pediatric
      isolates have increased slightly since 2005 and therapeutic decisions based on
      vancomycin MICs need to be made by considering the methodology used.

PMID- 19403770
TI  - Novel recombinant virus assay for measuring susceptibility of human
      immunodeficiency virus type 1 group M subtypes to clinically approved drugs.
AB  - Combination therapy can successfully suppress human immunodeficiency virus (HIV)
      replication in patients but selects for drug resistance, requiring subsequent
      resistance-guided therapeutic changes. This report describes the development and
      validation of a novel assay that offers a uniform method to measure
      susceptibility to all clinically approved HIV type 1 (HIV-1) drugs targeting
      reverse transcriptase (RT), protease (PR), integrase (IN), and viral entry. It is
      an assay in which the antiviral effect on infection within a single replication
      cycle is measured in triply transfected U87.CD4.CXCR4.CCR5 cells, based on
      homologous recombination between patient-derived amplicons and molecular proviral
      clones tagged with the enhanced green fluorescent protein (EGFP) reporter gene
      and from which certain viral genomic regions are removed. The deletions stretch
      from p17 codon 7 to PR codon 98 in pNL4.3-DeltagagPR-EGFP, from PR codons 1 to 99
      in pNL4.3-DeltaPR-EGFP, from RT codons 1 to 560 in pNL4.3-DeltaRT-EGFP, from IN
      codons 1 to 288 in pNL4.3-DeltaIN-EGFP, and from gp120 codon 34 to gp41 codon 237
      in pNL4.3-Deltaenv-EGFP. The optimized experimental conditions enable the
      investigation of patient samples regardless of viral subtype or coreceptor use.
      The extraction and amplification success rate for a set of clinical samples
      belonging to a broad range of HIV-1 group M genetic forms (A-J, CRF01-03, CRF05,
      and CRF12-13) and displaying a viral load range of 200 to >500,000 RNA copies/ml
      was 97%. The drug susceptibility measurements, based on discrimination between
      infected and noninfected cells on a single-cell level by flow cytometry, were
      reproducible, with coefficients of variation for resistance ranging from 7% to
      31%, and were consistent with scientific literature in terms of magnitude and
      specificity.

PMID- 19403771
TI  - Resistance of Acanthamoeba cysts to disinfection in multiple contact lens
      solutions.
AB  - Acanthamoebae are free-living amoebae found in the environment, including soil,
      freshwater, brackish water, seawater, hot tubs, and Jacuzzis. Acanthamoeba
      species can cause keratitis, a painful vision-threatening infection of the
      cornea, and fatal granulomatous encephalitis in humans. More than 20 species of
      Acanthamoeba belonging to morphological groups I, II, and III distributed in 15
      genotypes have been described. Among these, Acanthamoeba castellanii, A.
      polyphaga, and A. hatchetti are frequently identified as causing Acanthamoeba
      keratitis (AK). Improper contact lens care and contact with nonsterile water
      while wearing contact lenses are known risk factors for AK. During a recent
      multistate outbreak, AK was found to be associated with the use of Advanced
      Medical Optics Complete MoisturePlus multipurpose contact lens solution, which
      was hypothesized to have had insufficient anti-Acanthamoeba activity. As part of
      the investigation of that outbreak, we compared the efficacies of 11 different
      contact lens solutions against cysts of A. castellanii, A. polyphaga, and A.
      hatchetti (the isolates of all species were genotype T4), which were isolated in
      2007 from specimens obtained during the outbreak investigation. The data,
      generated with A. castellanii, A. polyphaga, and A. hatchetti cysts, suggest that
      the two contact lens solutions containing hydrogen peroxide were the only
      solutions that showed any disinfection ability, with 0% and 66% growth,
      respectively, being detected with A. castellanii and 0% and 33% growth,
      respectively, being detected with A. polyphaga. There was no statistically
      significant difference in disinfection efficacy between the 11 solutions for A.
      hatchetti.

PMID- 19403772
TI  - Use of reverse transcriptase PCR to subtype N1 to N9 neuraminidase genes of avian
      influenza viruses.
AB  - Reverse transcriptase PCR designed to amplify the N1 to N9 neuraminidase (NA)
      genes of avian influenza viruses detected 118 of the 119 NA genes tested (99.2%)
      in a subtype-specific manner. This technique successfully subtyped all 167 recent
      avian influenza viruses isolated from birds. Subtype specificity was confirmed by
      sequence analyses of all 285 PCR products.

PMID- 19403773
TI  - Adenovirus microsatellite reveals dynamics of transmission during a recent
      epidemic of human adenovirus serotype 14 infection.
AB  - This study reveals diverse-length polymorphisms in long mononucleotide repeats
      (microsatellites) in several serotypes of epidemic human respiratory adenovirus.
      The length of one of these microsatellites, a homopolymeric thymidine [poly(T)]
      repeat, is measured in 68 isolates of adenovirus serotype 14. These isolates were
      collected during a series of sudden and sometimes fatal outbreaks among both
      military recruits and civilians as the virus emerged for the first time in the
      United States in 2006 and 2007. The results demonstrate the usefulness of
      adenoviral microsatellites as high-resolution molecular strain markers. The
      described homopolymer is hypervariable in length, varying from 12 to 17 bp in the
      analyzed sample set. All intermediate lengths were identified in at least one
      isolate. Furthermore, the specific length of the marker is stable for significant
      periods of time (up to 7 months) at individual sites where the virus is in
      consistent circulation. The microsatellite also can maintain specific length
      identity through site-to-site transmission events, as determined by the analysis
      of isolates from three advanced training sites that appeared to be subject to
      pathogen transfer from one of the affected recruit training installations. Public
      database searches revealed that the polymorphic nature of the microsatellite
      extends to other species B serotypes, and that other polymorphic microsatellites
      can be identified readily in a variety of epidemic respiratory adenovirus clades.
      This study shows that microsatellites are a ubiquitous source of polymorphic
      markers for human adenoviruses and demonstrates their use through an
      epidemiological analysis of isolates from a recent North American epidemic.

PMID- 19403774
TI  - Reliability of the Vitek 2 yeast susceptibility test for detection of in vitro
      resistance to fluconazole and voriconazole in clinical isolates of Candida
      albicans and Candida glabrata.
AB  - The Vitek 2 yeast susceptibility test was evaluated by testing 122 Candida
      isolates against fluconazole and voriconazole. Excellent categorical agreement
      with the CLSI broth microdilution method was observed (97.5% for both the
      azoles). Moreover, the Vitek 2 system was able to identify all but 2 of 59
      investigated fluconazole-resistant organisms.

PMID- 19403775
TI  - Rapid molecular characterization of Clostridium difficile and assessment of
      populations of C. difficile in stool specimens.
AB  - Our laboratory has developed testing methods that use real-time PCR and
      pyrosequencing analysis to enable the rapid identification of potential
      hypervirulent Clostridium difficile strains. We describe a real-time PCR assay
      that detects four C. difficile genes encoding toxins A (tcdA) and B (tcdB) and
      the binary toxin genes (cdtA and cdtB), as well as a pyrosequencing assay that
      detects common deletions in the tcdC gene in less than 4 h. A subset of
      historical and recent C. difficile isolates (n = 31) was also analyzed by pulsed
      field gel electrophoresis to determine the circulating North American pulsed
      field (NAP) types that have been isolated in New York State. Thirteen different
      NAP types were found among the 31 isolates tested, 13 of which were NAP type 1
      strains. To further assess the best approach to utilizing our conventional and
      molecular methods, we studied the populations of C. difficile in patient stool
      specimens (n = 23). Our results indicated that 13% of individual stool specimens
      had heterogeneous populations of C. difficile when we compared the molecular
      characterization results for multiple bacterial isolates (n = 10). Direct
      molecular analysis of stool specimens gave results that correlated well with the
      results obtained with cultured stool specimens; the direct molecular analysis was
      rapid, informative, and less costly than the testing of multiple patient stool
      isolates.

PMID- 19403776
TI  - First insight into Mycobacterium tuberculosis epidemiology and genetic diversity
      in Trinidad and Tobago.
AB  - This report is based on a 1-year recruitment of all of the culture-positive
      Mycobacterium tuberculosis cases in Trinidad and Tobago (n = 132). The study
      population was characterized by a high male-to-female sex ratio of 4 and a human
      immunodeficiency virus-tuberculosis (TB) coinfection rate of 30%. It mainly
      occurred among African descendants, who represent 37.5% of the total population
      but 69.7% of all TB cases (P < 0.001). Spoligotyping resulted in 25 different
      patterns and 12 clusters (2 to 74 strains per cluster), with the predominance of
      a highly conserved spoligotype international type clone, SIT566.

PMID- 19403777
TI  - Shiga toxin, cytolethal distending toxin, and hemolysin repertoires in clinical
      Escherichia coli O91 isolates.
AB  - Shiga toxin (Stx)-producing Escherichia coli (STEC) strains of serogroup O91 are
      the most common human pathogenic eae-negative STEC strains. To facilitate
      diagnosis and subtyping of these pathogens, we genotypically and phenotypically
      characterized 100 clinical STEC O91 isolates. Motile strains expressed flagellar
      antigens H8 (1 strain), H10 (2 strains), H14 (52 strains), and H21 (20 strains)
      or were H nontypeable (Hnt) (10 strains); 15 strains were nonmotile. All
      nonmotile and Hnt strains possessed the fliC gene encoding the flagellin subunit
      of the H14 antigen (fliC(H14)). Most STEC O91 strains possessed enterohemorrhagic
      E. coli hlyA and expressed an enterohemolytic phenotype. Among seven stx alleles
      identified, stx(2dact), encoding mucus- and elastase-activatable Stx2d, was
      present solely in STEC O91:H21, whereas most strains of the other serotypes
      possessed stx(1). Moreover, only STEC O91:H21 possessed the cdt-V cluster,
      encoding cytolethal distending toxin V; the toxin was regularly expressed and was
      lethal to human microvascular endothelial cells. Infection with STEC O91:H21 was
      associated with hemolytic-uremic syndrome (P = 0.0015), whereas strains of the
      other serotypes originated mostly in patients with nonbloody diarrhea. We
      conclude that STEC O91 clinical isolates belong to at least four lineages that
      differ by H antigens/fliC types, stx genotypes, and non-stx putative virulence
      factors, with accumulation of virulence determinants in the O91:H21 lineage.
      Isolation of STEC O91 from patients' stools on enterohemolysin agar and the rapid
      initial subtyping of these isolates using fliC genotyping facilitate the
      identification of these emerging pathogens in clinical and epidemiological
      studies and enable prediction of the risk of a severe clinical outcome.

PMID- 19403778
TI  - Pharmacokinetic considerations regarding tigecycline for multidrug-resistant
      (MDR) Klebsiella pneumoniae or MDR Acinetobacter baumannii urosepsis.

PMID- 19403779
TI  - Campylobacter concisus: a new character in the Crohn's disease story?

PMID- 19403780
TI  - Towards a new reference test for surra in camels.
AB  - Current serological diagnosis of Trypanosoma evansi infection in camels is based
      on the native variable antigen type RoTat 1.2. The goal of this study was to
      develop a novel serological diagnostic test based on a nonvariable protein and
      freed from the use of rats or mice for its production. An enzyme-linked
      immunosorbent assay using a recombinant extracellular domain of invariant surface
      glycoprotein 75 (ELISA/rISG75) was developed and tested on a collection of 184
      camel sera. The results were compared to those obtained from three established
      antibody detection tests based on variable surface glycoprotein RoTat 1.2: an
      ELISA for T. evansi (ELISA/T. evansi), a card agglutination test for
      trypanosomiasis (CATT/T. evansi), and an immune trypanolysis (TL) assay. The
      ELISA/rISG75 and the ELISA/T. evansi showed a sensitivity of 94.6% (95%
      confidence interval [CI], 87.8 to 98.2%, at 19% positivity cutoff value) and
      98.9% (95% CI, 94.1 to 99.8, at 12% positivity cutoff value), respectively. The
      ELISA/rISG75 had 100% specificity (CI, 95.9 to 100%), while the ELISA/T. evansi
      showed 98.9% specificity (CI, 95.9 to 100%). The ELISA/rISG75 demonstrated an
      almost perfect agreement with the TL assay, the CATT/T. evansi, and the ELISA/T.
      evansi, with kappa scores of at least 0.94. The ELISA/rISG75, having a
      performance comparable to that of the gold standard (the TL assay) and being
      independent of antigenic variation, may become a new reference test for surra in
      camels. It opens avenues for the diagnosis of T. evansi infections in other hosts
      as well as for the development of a pan-Trypanozoon test for detection of
      Trypanosoma brucei brucei, T. b. gambiense, T. b. rhodesiense, T. evansi, and T.
      equiperdum.

PMID- 19403781
TI  - Antibodies to pneumococcal proteins PhtD, CbpA, and LytC in Filipino pregnant
      women and their infants in relation to pneumococcal carriage.
AB  - This study focuses on the immunogenicity of the following three pneumococcal
      vaccine candidate proteins in Filipino infants, all inducing protection in animal
      models: pneumococcal histidine triad protein D (PhtD), choline binding protein A
      (CbpA), and the lysozyme LytC. The immunoglobulin G antibody concentrations to
      PhtD, its putative, protective, and exposed C-terminal fragment (PhtD C), CbpA,
      and LytC were measured by enzyme immunoassay in 52 serum samples from pregnant
      women, 39 cord blood samples, and consecutive serum samples (n = 263) from 52
      newborns between 6 weeks and 10 months of age scheduled to be taken at six time
      points. A nasopharyngeal swab to detect pneumococcal carriage was taken parallel
      to the serum samples. The antibody concentrations in the cord blood samples were
      similar to those in the samples from the mothers. In infant sera, the geometric
      mean antibody concentrations (GMCs) for all three proteins decreased until the
      age of 18 weeks and started to increase after that age, suggesting that the
      infants' own antibody production started close to the age of 4 to 5 months. The
      increase in GMCs by age, most clear-cut for CbpA, was associated with
      pneumococcal carriage. Anti-PhtD concentrations were higher than anti-PhtD C
      concentrations but correlated well (r of 0.89 at 10.5 months), suggesting that
      antibodies are directed to the supposedly exposed and protective C-terminal part
      of PhtD. Our results show that young children are able to develop an antibody
      response to PhtD, CbpA, and LytC and encourage the development of pneumococcal
      protein vaccines for this age group.

PMID- 19403782
TI  - 9-O-acetylated sialoglycoproteins are important immunomodulators in Indian
      visceral leishmaniasis.
AB  - Overexpression of disease-associated 9-O-acetylated sialoglycoproteins (9-O
      AcSGPs) on peripheral blood mononuclear cells (PBMC) of visceral leishmaniasis
      (VL) patients (PBMC(VL)) compared to their levels of expression in healthy
      individuals has been demonstrated using a lectin, achatinin-H, with specificity
      toward 9-O-acetylated sialic acid derivatives alpha2-6 linkage with subterminal N
      acetylgalactosamine (9-O-AcSAalpha2-6GalNAc). The decreased presence of disease
      associated 9-O-AcSGPs on different immune cells of parasitologically cured
      individuals after successful treatment relative to the levels in patients with
      active VL prior to treatment was demonstrated. However, their contributory role
      as immunomodulatory determinants on PBMC(VL) remained unexplored. Accordingly, 9
      O-AcSGPs on PBMC(VL) were sensitized with achatinin-H, leading to their enhanced
      proliferation compared to that observed with different known mitogens or parasite
      antigen. This lymphoproliferative response was characterized by evaluation of the
      TH1/TH2 response by intracellular staining and enzyme-linked immunosorbent assay
      for secreted cytokines, and the results were corroborated by their genetic
      expression. Sensitized PBMC(VL) evidenced a mixed TH1/TH2 cellular response with
      a predominance of the TH1 response, indicating the ability of 9-O-AcSGPs to
      modulate the host cell toward a favorable response. Interestingly, the humoral
      and cellular responses showed a good correlation. Further, high levels of anti-9
      O-AcSGP antibodies with an order of distribution of immunoglobulin M (IgM) > IgG1
      = IgG3 > IgG4 > IgG2 > IgE could be explained by a mixed TH1/TH2 response. A good
      correlation of enhanced 9-O-AcSGPs with both the cell-mediated (r = 0.98) and
      humoral (r = 0.99) response was observed. In summary, it may be concluded that
      sensitization of 9-O-AcSGPs on PBMC(VL) may provide a basis for the modulation of
      the host's immune response by their controlled expression, leading to a
      beneficial immune response and influencing the disease pathology.

PMID- 19403783
TI  - Evaluation of an immunofiltration assay that detects immunoglobulin M antibodies
      against the ZEBRA protein for the diagnosis of Epstein-Barr virus infectious
      mononucleosis in immunocompetent patients.
AB  - The performance of an immunofiltration assay (IMFA) that detects immunoglobulin M
      (IgM) antibodies to the Epstein-Barr virus (EBV) ZEBRA (BamHI Z EBV replication
      activator) protein was evaluated for the diagnosis of EBV infectious
      mononucleosis (IM) in immunocompetent patients. The test panel consisted of 47
      sera displaying an EBV-specific antibody profile compatible with an acute primary
      EBV infection from patients with clinical and biological features of EBV IM, 20
      sera from healthy individuals either with a past EBV infection or who were EBV
      seronegative, 20 sera displaying an equivocal EBV antibody pattern (viral capsid
      antigen IgG positive [VCA IgG+], VCA IgM+, and EBV nuclear antigen-1 IgG+), and
      15 sera obtained from patients with a mononucleosis-like syndrome owing to
      cytomegalovirus, human herpesvirus 6, or parvovirus B19. Overall, the sensitivity
      and the specificity of the assay were found to be 92.5%, and 97.3%, respectively.
      The sensitivity of the assay for the diagnosis of heterophile antibody-negative
      EBV IM was 86.2%. The IMFA is rapid, easy to perform, and, thus, suitable for
      point-of-care testing, and it may be used as a first-line test for the diagnosis
      of acute EBV IM in immunocompetent patients.

PMID- 19403784
TI  - Clinical features that affect indirect-hemagglutination-assay responses to
      Burkholderia pseudomallei.
AB  - Melioidosis, a disease endemic to northern Australia and Southeast Asia, is
      caused by the soil saprophyte Burkholderia pseudomallei. The indirect
      hemagglutination assay (IHA) is the most frequently used serological test to help
      confirm exposure to the causative organism. However, despite culture-confirmed
      disease, patients often have a negative IHA result at presentation and
      occasionally fail to seroconvert in serial testing. We retrospectively examined
      results for all patients with culture-confirmed melioidosis from our laboratory
      between January 1996 and August 2008. One hundred forty patients had a recorded
      IHA titer at presentation, 71 of which were positive at a titer of 1:40 or
      greater. Fifty-three patients went on to have subsequent IHAs 1 month or more
      after presentation. The relationships between IHA responses and clinical features
      were examined. The presence of bacteremia was significantly associated with a
      negative IHA at presentation. The coexistence of diabetes was associated with the
      presence of a positive IHA at presentation. In total, 14 patients (26%)
      demonstrated persistently negative IHA titers upon serial testing. No clinical
      factors were found to be significantly associated with this phenomenon.
      Supplementary testing using melioidosis-specific immunoglobulin G by EIA
      demonstrated different effects, with only Aboriginal or Torres Straits Islander
      ethnicity being significantly associated with a positive EIA at presentation.
      Reasons for these findings are examined, and directions for future research are
      discussed.

PMID- 19403785
TI  - Relationships between work satisfaction, emotional exhaustion and mental health
      among Swiss primary care physicians.
AB  - BACKGROUND: Work-related satisfaction is an important determinant of quality of
      care. However, its relationship with doctors' mental health is poorly understood.
      It could have an independent beneficial effect on mental health (direct
      association) or simply reduce the impact of work stress on mental health
      (moderating or 'buffering' role). METHODS: One thousand seven hundred and thirty
      two Swiss primary care physicians (824 board-certified generalists, 436 general
      internists, 162 paediatricians, 147 internal medicine specialists and 163
      physicians without specialty qualification) completed a mailed questionnaire.
      Previously, validated instruments were used to measure mental health (SF-12),
      emotional exhaustion [Maslach Burnout Inventory (MBI)] and work-related
      satisfaction. Linear regression models with mental health as dependant variable
      were used to study the relationships between these variables. Differences in
      mental health scores were standardized to represent a one standard deviation (SD)
      difference in the other scales [standardized beta coefficients (SBC)]. RESULTS:
      In multivariate analyses, higher levels of mental health were found in
      respondents with higher work-related satisfaction with current income and social
      prestige (SBC 1.04) and professional relations (SBC 0.57), and in respondents
      with lower emotional exhaustion (SBC -4.98) and higher personal accomplishment
      scores (SBC 1.72). Interaction terms between these dimensions of work-related
      satisfaction and emotional exhaustion were significant, supporting a 'buffering'
      role of these dimensions. CONCLUSION: Work-satisfaction with current income,
      social prestige and professional relations are important correlates of mental
      health among primary care physicians, as well as emotional exhaustion. Higher
      levels of these dimensions of work-related satisfaction seems to mitigate the
      relationship between emotional exhaustion and physicians' mental health.

PMID- 19403786
TI  - Is depression associated with health risk-related behaviour clusters in adults?
AB  - BACKGROUND: Depressive disorders have been linked to health risk-related
      behaviours (HRBs) considered separately. Our objective was to study whether
      depression is associated with the co-occurrence of HRBs in adults. METHODS: A
      sample of 17 355 subjects aged > or =18 years, derived from the 2002-03 cross
      sectional Decennial Health Survey; probable depression was assessed with the CES
      D scale. A cluster analysis of various HRBs (tobacco use, alcohol use, binge
      drinking, physical inactivity, certain eating habits) was used to study their co
      occurrence. Multiple regressions adjusted on demographic and socio-economic
      characteristics, Body Mass Index and chronic illnesses were performed to study
      associations between probable depression and the HRBs clusters obtained. RESULTS:
      Five clusters were observed evidencing a gradient of cumulative exposure to HRBs:
      'healthy lifestyles (Cluster 1), 'non-daily-consumers-fruit-and-green-vegetables'
      (Cluster 2), 'regular alcohol users' (Cluster 3), 'daily smokers' (Cluster 4) and
      'cumulate risk takers' (Cluster 5). Compared with Cluster 1, positive
      associations were found between probable depression and Clusters 2, 4 and 5: OR
      1.49 (95% CI 1.26-1.76) for Cluster 2; OR 1.81 (95% CI 1.54-2.12) for Cluster 4;
      OR 2.05 (95% CI 1.68-2.51) for Cluster 5. For Cluster 3, no association was
      found: OR 1.01 (95% CI 0.84-1.21). CONCLUSIONS: HRBs tend to co-occur in the
      general population, more frequently in case of probable depression. Further
      research is necessary to disentangle the direction of the links between
      depression and HRB clusters. Nonetheless, these results question the classic
      design of education campaigns considering HRBs separately. Moreover, screening
      for depression should be systematic during prevention consultations and various
      HRBs should be monitored when treating depressive patients.

PMID- 19403787
TI  - Anterior thalamic lesions stop synaptic plasticity in retrosplenial cortex
      slices: expanding the pathology of diencephalic amnesia.
AB  - Recent, convergent evidence places the anterior thalamic nuclei at the heart of
      diencephalic amnesia. However, the reasons for the severe memory loss in
      diencephalic amnesia remain unknown. A potential clue comes from the dense,
      reciprocal connections between the anterior thalamic nuclei and retrosplenial
      cortex, another region vital for memory. We now report a loss of synaptic
      plasticity [long-term depression (LTD)] in rat retrosplenial cortex slices months
      following an anterior thalamic lesion. The loss of LTD was lamina-specific,
      occurring only in superficial layers of the cortex and was associated with a
      decrease in GABA(A)-mediated inhibitory transmission. As retrosplenial cortex is
      itself vital for memory, this distal lesion effect will amplify the impact of
      anterior thalamic lesions. These findings not only provide novel insights into
      the functional pathology of diencephalic amnesia and have implications for the
      aetiology of the posterior cingulate hypoactivity in Alzheimer's disease, but
      also show how distal changes in plasticity could contribute to diaschisis.

PMID- 19403789
TI  - Understanding oriental medicine using a systems approach.
AB  - Two international meetings, the International Physiome Symposium 2008 and the
      Workshop on Systems Biology (SB) and Oriental Medicine (OM), were held to discuss
      the most appropriate scientific tools to research OM. Participants agreed that
      since OM is holistic medicine it needs a systems approach such as SB. However, SB
      itself is still a long way from identifying the high-level organization processes
      in the biological system that might correlate with concepts in OM. As such, a
      modest goal of launching a project to examine the problems of translation and
      interpretation of OM concepts would be the first step.

PMID- 19403788
TI  - In vivo measurement of axon diameter distribution in the corpus callosum of rat
      brain.
AB  - Here, we present the first in vivo non-invasive measurement of the axon diameter
      distribution in the rat corpus callosum. Previously, this measurement was only
      possible using invasive histological methods. The axon diameter, along with other
      physical properties, such as the intra-axonal resistance, membrane resistance and
      capacitance etc. helps determine many important functional properties of nerves,
      such as their conduction velocity. In this work, we provide a novel magnetic
      resonance imaging method called AxCaliber, which can resolve the distinct
      signatures of trapped water molecules diffusing within axons as well as water
      molecules diffusing freely within the extra-axonal space. Using a series of
      diffusion weighted magnetic resonance imaging brain scans, we can reliably infer
      both the distribution of axon diameters and the volume fraction of these axons
      within each white matter voxel. We were able to verify the known microstructural
      variation along the corpus callosum of the rat from the anterior (genu) to
      posterior (splenium) regions. AxCaliber yields a narrow distribution centered
      approximately 1 microm in the genu and splenium and much broader distributions
      centered approximately 3 microm in the body of the corpus callosum. The axon
      diameter distribution found by AxCaliber is generally broader than those usually
      obtained by histology. One factor contributing to this difference is the
      significant tissue shrinkage that results from histological preparation. To that
      end, AxCaliber might provide a better estimate of the in vivo morphology of white
      matter. Being a magnetic resonance imaging based methodology, AxCaliber has the
      potential to be used in human scanners for morphological studies of white matter
      in normal and abnormal development, and white matter related diseases.

PMID- 19403790
TI  - The simple life: on the benefits of low self-complexity.
AB  - This article examines the spillover amplification hypothesis, which proposes that
      because people lower in self-complexity experience stronger responses to life
      events they will show relatively better well-being in the presence of positive
      factors (e.g., better social support) and relatively poorer well-being in the
      presence of negative factors (e.g., a history of negative experiences). Across
      three studies, support for spillover amplification was found. Specifically,
      people lower in self-complexity revealed greater self-esteem, less depression,
      and fewer illnesses when they had greater social support (Study 1) and more
      desirable personality characteristics (Study 2), yet they had poorer well-being
      if they had a history of many negative life events (Study 3). Thus, how one's
      self-concept is represented in memory moderates the relationship between many
      well-established factors and well-being.

PMID- 19403791
TI  - The source effect: person descriptions by self versus others have differential
      effects on impression formation.
AB  - Self-presentation via favorable self-descriptions may not lead to the desired
      impression, whereas positive descriptions by others may be more effective because
      they seem less susceptible to motivated bias. In four experiments, we
      investigated whether person descriptions have more impact on impressions when
      provided by third parties than by targets themselves. Results showed that target
      impressions were consistently more in line with the target description when
      positive sociability-related or positive competency-related information was given
      by a third party than by the target. This source effect always occurred for
      ratings of claimed traits. In addition, ratings of the target's sociability were
      also affected when the claim was about competency. Source effects were not
      obtained for negative self-descriptions. The results are discussed in terms of
      the presumed underlying process on the basis of mediation data.

PMID- 19403792
TI  - Stigma management and well-being: the role of perceived social support, emotional
      processing, and suppression.
AB  - Lesbians and gay men frequently make decisions about concealing or disclosing
      their stigmatized identity. Past research has found that disclosing one's sexual
      orientation is often beneficial. This study aimed to answer the question, "why?".
      Specifically, this study tested a model in which perceived social support,
      emotional processing, and suppression mediate the association between disclosure
      and well-being. To capture disclosure decisions in real time, participants
      completed a 2-week daily diary study and a 2-month follow-up survey. As expected,
      participants generally reported greater well-being on days when they disclosed
      (vs. concealed) their sexual orientation. Perceived social support was a
      consistent predictor of well-being and mediator of the association between
      disclosure and well-being. Although less consistent across time and measures,
      emotional processing and to a lesser extent suppression were also significantly
      associated with disclosure and well-being. This research advances the scientific
      understanding of concealable stigmatized identities and their impact on
      individual well-being.

PMID- 19403794
TI  - Model-based reinforcement learning under concurrent schedules of reinforcement in
      rodents.
AB  - Reinforcement learning theories postulate that actions are chosen to maximize a
      long-term sum of positive outcomes based on value functions, which are subjective
      estimates of future rewards. In simple reinforcement learning algorithms, value
      functions are updated only by trial-and-error, whereas they are updated according
      to the decision-maker's knowledge or model of the environment in model-based
      reinforcement learning algorithms. To investigate how animals update value
      functions, we trained rats under two different free-choice tasks. The reward
      probability of the unchosen target remained unchanged in one task, whereas it
      increased over time since the target was last chosen in the other task. The
      results show that goal choice probability increased as a function of the number
      of consecutive alternative choices in the latter, but not the former task,
      indicating that the animals were aware of time-dependent increases in arming
      probability and used this information in choosing goals. In addition, the choice
      behavior in the latter task was better accounted for by a model-based
      reinforcement learning algorithm. Our results show that rats adopt a decision
      making process that cannot be accounted for by simple reinforcement learning
      models even in a relatively simple binary choice task, suggesting that rats can
      readily improve their decision-making strategy through the knowledge of their
      environments.

PMID- 19403795
TI  - Stimulus-outcome learnability differentially activates anterior cingulate and
      hippocampus at feedback processing.
AB  - Memory systems are known to be influenced by feedback and error processing, but
      it is not well known what aspects of outcome contingencies are related to
      different memory systems. Here we use the Rescorla-Wagner model to estimate
      prediction errors in an fMRI study of stimulus-outcome association learning. The
      conditional probabilities of outcomes for a given stimulus are manipulated so
      that associations are either learnable or unlearnable (pseudorandom). The delay
      between stimulus and outcome is jittered so that we can separately compare
      activity for either stimulus processing or feedback processing. We find that
      hippocampus and anterior cingulate are differentially active primarily at
      feedback processing: Learnable associations are correlated with significantly
      more hippocampal activity and significantly less anterior cingulate activity than
      unlearnable associations. We also find that positive prediction errors modulate
      feedback processing in the midbrain for both types of associations. We suggest
      that learnable associations use more declarative memory, unlearnable associations
      involve more uncertainty monitoring, and, in both kinds of associations, positive
      prediction errors provide a reinforcement signal.

PMID- 19403793
TI  - Intrahippocampal infusions of anisomycin produce amnesia: contribution of
      increased release of norepinephrine, dopamine, and acetylcholine.
AB  - Intra-amygdala injections of anisomycin produce large increases in the release of
      norepinephrine (NE), dopamine (DA), and serotonin in the amygdala. Pretreatment
      with intra-amygdala injections of the beta-adrenergic receptor antagonist
      propranolol attenuates anisomycin-induced amnesia without reversing the
      inhibition of protein synthesis, and injections of NE alone produce amnesia.
      These findings suggest that abnormal neurotransmitter responses may be the basis
      for amnesia produced by inhibition of protein synthesis. The present experiment
      extends these findings to the hippocampus and adds acetylcholine (ACh) to the
      list of neurotransmitters affected by anisomycin. Using in vivo microdialysis at
      the site of injection, release of NE, DA, and ACh was measured before and after
      injections of anisomycin into the hippocampus. Anisomycin impaired inhibitory
      avoidance memory when rats were tested 48 h after training and also produced
      substantial increases in local release of NE, DA, and ACh. In an additional
      experiment, pretreatment with intrahippocampal injections of propranolol prior to
      anisomycin and training significantly attenuated anisomycin-induced amnesia. The
      disruption of neurotransmitter release patterns at the site of injection appears
      to contribute significantly to the mechanisms underlying amnesia produced by
      protein synthesis inhibitors, calling into question the dominant interpretation
      that the amnesia reflects loss of training-initiated protein synthesis necessary
      for memory formation. Instead, the findings suggest that proteins needed for
      memory formation are available prior to an experience, and that post
      translational modifications of these proteins may be sufficient to enable the
      formation of new memories.

PMID- 19403797
TI  - Visual object pattern separation deficits in nondemented older adults.
AB  - Young and nondemented older adults were tested on a continuous recognition memory
      task requiring visual pattern separation. During the task, some objects were
      repeated across trials and some objects, referred to as lures, were presented
      that were similar to previously presented objects. The lures resulted in
      increased interference and an increased need for pattern separation. For each
      object, the participant was asked to indicate whether (1) this was the first time
      the object was seen (new), (2) the object was seen previously (old), or (3) the
      object was similar to a previous object (similar). Older adults were able to
      correctly identify objects as old or new as well as young adults; however, older
      adults were impaired when identifying lures as similar. Therefore, pattern
      separation may be less efficient in older adults resulting in poorer recognition
      memory performance when interference is increased.

PMID- 19403796
TI  - Fatty acid amide hydrolase (FAAH) inhibition enhances memory acquisition through
      activation of PPAR-alpha nuclear receptors.
AB  - Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of
      anandamide (a cannabinoid CB(1)-receptor ligand) and oleoylethanolamide and
      palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome
      proliferator-activated nuclear receptors, PPAR-alpha) when and where they are
      naturally released in the brain. Using a passive-avoidance task in rats, we found
      that memory acquisition was enhanced by the FAAH inhibitor URB597 or by the PPAR
      alpha agonist WY14643, and these enhancements were blocked by the PPAR-alpha
      antagonist MK886. These findings demonstrate novel mechanisms for memory
      enhancement by activation of PPAR-alpha, either directly by administering a PPAR
      alpha agonist or indirectly by administering a FAAH inhibitor.

PMID- 19403798
TI  - Simultaneous overexpression of Oct4 and Nanog abrogates terminal myogenesis.
AB  - Oct4 and Nanog are two embryonic stem (ES) cell-specific transcription factors
      that play critical roles in the maintenance of ES cell pluripotency. In this
      study, we investigated the effects of Oct4 and Nanog expression on the
      differentiation state of myogenic cells, which is sustained by a strong positive
      feedback loop. Oct4 and Nanog, either independently or simultaneously, were
      overexpressed in C2C12 myoblasts, and the expression of myogenic lineage-specific
      genes and terminal differentiation was observed by RT-PCR. Overexpression of Oct4
      in C2C12 cultures repressed, while exogenous Nanog did not significantly alter
      C2C12 terminal differentiation. The expression of Pax7 was reduced in all Oct4
      overexpressing myoblasts, and we identified a major Oct4-binding site in the Pax7
      promoter. Simultaneous expression of Oct4 and Nanog in myoblasts inhibited the
      formation of myotubes, concomitant with a reduction in the endogenous levels of
      hallmark myogenic markers. Furthermore, overexpression of Oct4 and Nanog induced
      the expression of their endogenous counterparts along with the expression of
      Sox2. Using mammalian two-hybrid assays, we confirmed that Oct4 functions as a
      transcriptional repressor whereas Nanog functions as a transcriptional activator
      during muscle terminal differentiation. Importantly, in nonobese diabetic (NOD)
      severe combined immunodeficiency (SCID) mice, the pluripotency of C2C12 cells was
      conferred by overexpression of Oct4 and Nanog. These results suggest that Oct4 in
      cooperation with Nanog strongly suppresses the myogenic differentiation program
      and promotes pluripotency in myoblasts.

PMID- 19403799
TI  - Novel epigenetic regulation of skeletal muscle myosin heavy chain genes. Focus on
      "Differential epigenetic modifications of histones at the myosin heavy chain
      genes in fast and slow skeletal muscle fibers and in response to muscle
      unloading".

PMID- 19403800
TI  - Role of the glutamate 185 residue in proton translocation mediated by the proton
      coupled folate transporter SLC46A1.
AB  - The proton-coupled folate transporter (PCFT) SLC46A1 mediates uphill folate
      transport into enterocytes in proximal small intestine coupled to the inwardly
      directed proton gradient. Hereditary folate malabsorption is due to loss-of
      function mutations in the PCFT gene. This study addresses the functional role of
      conserved charged amino acid residues within PCFT transmembrane domains with a
      detailed analysis of the PCFT E185 residue. D156A-, E185A-, E232A-, R148A-, and
      R376A-PCFT mutants lost function at pH 5.5, as assessed by transient transfection
      in folate transport-deficient HeLa cells. At pH 7.4, function was preserved only
      for E185A-PCFT. Loss of function for E185A-PCFT at pH 5.5 was due to an eightfold
      decrease in the [(3)H]methotrexate (MTX) influx V(max); the MTX influx K(t) was
      identical to that of wild-type (WT)-PCFT (1.5 microM). Consistent with the
      intrinsic functionality of E185A-PCFT, [(3)H]MTX influx at pH 5.5 or 7.4 was
      trans-stimulated in cells preloaded with nonlabeled MTX or 5
      formyltetrahydrofolate. Replacement of E185 with Leu, Cys, His, or Gln resulted
      in a phenotype similar to E185A-PCFT. However, there was greater preservation of
      activity (approximately 38% of WT) for the similarly charged E185D-PCFT at pH
      5.5. All E185 substitution mutants were biotin accessible at the plasma membrane
      at a level comparable to WT-PCFT. These observations suggest that the E185
      residue plays an important role in the coupled flows of protons and folate
      mediated by PCFT. Coupling appears to have a profound effect on the maximum rate
      of transport, consistent with augmentation of a rate-limiting step in the PCFT
      transport cycle.

PMID- 19403802
TI  - Quality of life: a fertile field for inquiry.

PMID- 19403803
TI  - Micromanaging oligodendrocyte differentiation by noncoding RNA: toward a better
      understanding of the lineage commitment process.

PMID- 19403801
TI  - MAGI-1 interacts with Slo1 channel proteins and suppresses Slo1 expression on the
      cell surface.
AB  - Large conductance Ca(2+)-activated K(+) (BK(Ca)) channels encoded by the Slo1
      gene (also known as KCNMA1) are physiologically important in a wide range of cell
      types and form complexes with a number of other proteins that affect their
      function. We performed a yeast two-hybrid screen to identify proteins that
      interact with BK(Ca) channels using a bait construct derived from domains in the
      extreme COOH-terminus of Slo1. A protein known as membrane-associated guanylate
      kinase with inverted orientation protein-1 (MAGI-1) was identified in this
      screen. MAGI-1 is a scaffolding protein that allows formation of complexes
      between certain transmembrane proteins, actin-binding proteins, and other
      regulatory proteins. MAGI-1 is expressed in a number of tissues, including
      podocytes and the brain. The interaction between MAGI-1 and BK(Ca) channels was
      confirmed by coimmunoprecipitation and glutathione S-transferase pull-down assays
      in differentiated cells of a podocyte cell line and in human embryonic kidneys
      (HEK)293T cells transiently coexpressing MAGI-1a and three different COOH
      terminal Slo1 variants. Coexpression of MAGI-1 with Slo1 channels in HEK-293T
      cells results in a significant reduction in the surface expression of Slo1, as
      assessed by cell-surface biotinylation assays, confocal microscopy, and whole
      cell recordings. Partial knockdown of endogenous MAGI-1 expression by small
      interfering RNA (siRNA) in differentiated podocytes increased the surface
      expression of endogenous Slo1 as assessed by electrophysiology and cell-surface
      biotinylation assays, whereas overexpression of MAGI-1a reduced steady-state
      voltage-evoked outward current through podocyte BK(Ca) channels. These data
      suggest that MAGI-1 plays a role in regulation of surface expression of BK(Ca)
      channels in the kidney and possibly in other tissues.

PMID- 19403804
TI  - Kalirin-7: linking spine plasticity and behavior.

PMID- 19403805
TI  - Parallel use of two behavioral mechanisms for chemotaxis in Caenorhabditis
      elegans.
AB  - Caenorhabditis elegans shows chemotaxis to various odorants and water-soluble
      chemoattractants such as NaCl. Previous studies described the pirouette mechanism
      for chemotaxis, in which C. elegans quickly changes the direction of locomotion
      by using a set of stereotyped behaviors, a pirouette, in response to a decrease
      in the concentration of the chemical. Here, we report the discovery of a second
      mechanism for chemotaxis, called the weathervane mechanism. In this strategy
      animals respond to a spatial gradient of chemoattractant and gradually curve
      toward higher concentration of the chemical. By computer simulation, we find that
      both of these mechanisms contribute to chemotaxis and both mechanisms need to act
      in parallel for efficient chemotaxis. Using laser ablation of individual neurons
      to examine the underlying neural circuit, we find the ASE sensory neurons and AIZ
      interneurons are essential for both the pirouette and weathervane mechanisms in
      chemotaxis to NaCl. Salt-conditioned animals show reversed responses in both of
      these behaviors, leading to avoidance of NaCl. These results provide a platform
      for detailed molecular and cellular analyses of chemotaxis and its plasticity in
      this model organism.

PMID- 19403806
TI  - Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in
      depression-related behavior.
AB  - No animal models replicate the complexity of human depression. However, a number
      of behavioral tests in rodents are sensitive to antidepressants and may thus tap
      important underlying biological factors. Such models may also offer the best
      opportunity to discover novel treatments. Here, we used several of these models
      to test the hypothesis that the acid-sensing ion channel-1a (ASIC1a) might be
      targeted to reduce depression. Genetically disrupting ASIC1a in mice produced
      antidepressant-like effects in the forced swim test, the tail suspension test,
      and following unpredictable mild stress. Pharmacologically inhibiting ASIC1a also
      had antidepressant-like effects in the forced swim test. The effects of ASIC1a
      disruption in the forced swim test were independent of and additive to those of
      several commonly used antidepressants. Furthermore, ASIC1a disruption interfered
      with an important biochemical marker of depression, the ability of stress to
      reduce BDNF in the hippocampus. Restoring ASIC1a to the amygdala of ASIC1a(-/-)
      mice with a viral vector reversed the forced swim test effects, suggesting that
      the amygdala is a key site of ASIC1a action in depression-related behavior. These
      data are consistent with clinical studies emphasizing the importance of the
      amygdala in mood regulation, and suggest that ASIC1a antagonists may effectively
      combat depression.

PMID- 19403808
TI  - Early deficits in spatial memory and theta rhythm in experimental temporal lobe
      epilepsy.
AB  - Patients with temporal lobe epilepsy (TLE), the most common form of epilepsy in
      adults, often display cognitive deficits. The time course and underlying
      mechanisms of cognitive decline remain unknown during epileptogenesis (the
      process leading to epilepsy). Using the rat pilocarpine model of TLE, we
      performed a longitudinal study to assess spatial and nonspatial cognitive
      performance during epileptogenesis. In parallel, we monitored interictal-like
      activity (ILA) in the hippocampal CA1 region, as well as theta oscillations, a
      brain rhythm central to numerous cognitive processes. Here, we report that
      spatial memory was altered soon after pilocarpine-induced status epilepticus,
      i.e., already during the seizure-free, latent period. Spatial deficits correlated
      with a decrease in the power of theta oscillations but not with the frequency of
      ILA. Spatial deficits persisted when animals had spontaneous seizures (chronic
      stage) without further modification. In contrast, nonspatial memory performances
      remained unaffected throughout. We conclude that the reorganization of
      hippocampal circuitry that immediately follows the initial insult can affect
      theta oscillation mechanisms, in turn, resulting in deficits in hippocampus
      dependent memory tasks. These deficits may be dissociated from the process that
      leads to epilepsy itself but could instead constitute, as ILA, early markers in
      at-risk patients and/or provide beneficial therapeutic targets.

PMID- 19403810
TI  - Activity-dependent repression of Cbln1 expression: mechanism for developmental
      and homeostatic regulation of synapses in the cerebellum.
AB  - Cbln1, which belongs to the C1q/tumor necrosis factor superfamily, is released
      from cerebellar granule cells and plays a crucial role in forming and maintaining
      excitatory synapses between parallel fibers (PFs; axons of granule cells) and
      Purkinje cells not only during development but also in the adult cerebellum.
      Although neuronal activity is known to cause morphological changes at synapses,
      how Cbln1 signaling is affected by neuronal activity remains unclear. Here, we
      show that chronic stimulation of neuronal activity by elevating extracellular
      K(+) levels or by adding kainate decreased the expression of cbln1 mRNA within
      several hours in mature granule cells in a manner dependent on L-type voltage
      dependent Ca(2+) channels and calcineurin. Chronic activity also reduced Cbln1
      protein levels within a few days, during which time the number of excitatory
      synapses on Purkinje cell dendrites was reduced; this activity-induced reduction
      of synapses was prevented by the addition of exogenous Cbln1 to the culture
      medium. Therefore, the activity-dependent downregulation of cbln1 may serve as a
      new presynaptic mechanism by which PF-Purkinje cell synapses adapt to chronically
      elevated activity, thereby maintaining homeostasis. In addition, the expression
      of cbln1 mRNA was prevented when immature granule cells were maintained in high
      K(+) medium. Since immature granule cells are chronically depolarized before
      migrating to the internal granule layer, this depolarization-dependent regulation
      of cbln1 mRNA expression may also serve as a developmental switch to facilitate
      PF synapse formation in mature granule cells in the internal granule layer.

PMID- 19403809
TI  - p75 and TrkA signaling regulates sympathetic neuronal firing patterns via
      differential modulation of voltage-gated currents.
AB  - Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic
      factor (BDNF) act through the tropomyosin-related receptor tyrosine kinases (Trk)
      and the pan-neurotrophin receptor (p75) to regulate complex developmental and
      functional properties of neurons. While NGF activates both receptor types in
      sympathetic neurons, differential signaling through TrkA and p75 can result in
      widely divergent functional outputs for neuronal survival, growth, and synaptic
      function. Here we show that TrkA and p75 signaling pathways have opposing effects
      on the firing properties of sympathetic neurons, and define a mechanism whereby
      the relative level of signaling through these two receptors sets firing patterns
      via coordinate regulation of a set of ionic currents. We show that signaling
      through the p75 pathway causes sympathetic neurons to fire in a phasic pattern
      showing marked accommodation. Signaling through the NGF-specific TrkA, on the
      other hand, causes cells to fire tonically. Neurons switch rapidly between firing
      patterns, on the order of minutes to hours. We show that changes in firing
      patterns are caused by neurotrophin-dependent regulation of at least four voltage
      gated currents: the sodium current and the M-type, delayed rectifier, and calcium
      dependent potassium currents. Neurotrophin release, and thus receptor activation,
      varies among somatic tissues and physiological state. Thus, these data suggest
      that target-derived neurotrophins may be an important determinant of the
      characteristic electrical properties of sympathetic neurons and therefore
      regulate the functional output of the sympathetic nervous system.

PMID- 19403807
TI  - Protracted withdrawal from alcohol and drugs of abuse impairs long-term
      potentiation of intrinsic excitability in the juxtacapsular bed nucleus of the
      stria terminalis.
AB  - The juxtacapsular bed nucleus of the stria terminalis (jcBNST) is activated in
      response to basolateral amygdala (BLA) inputs through the stria terminalis and
      projects back to the anterior BLA and to the central nucleus of the amygdala.
      Here we show a form of long-term potentiation of the intrinsic excitability (LTP
      IE) of jcBNST neurons in response to high-frequency stimulation of the stria
      terminalis. This LTP-IE, which was characterized by a decrease in the firing
      threshold and increased temporal fidelity of firing, was impaired during
      protracted withdrawal from self-administration of alcohol, cocaine, and heroin.
      Such impairment was graded and was more pronounced in rats that self-administered
      amounts of the drugs sufficient to maintain dependence. Dysregulation of the
      corticotropin-releasing factor (CRF) system has been implicated in manifestation
      of protracted withdrawal from dependent drug use. Administration of the selective
      corticotropin-releasing factor receptor 1 (CRF(1)) antagonist R121919 [2,5
      dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino-pyrazolo[1,5
      a]pyrimidine)], but not of the CRF(2) antagonist astressin(2)-B, normalized
      jcBNST LTP-IE in animals with a history of alcohol dependence; repeated, but not
      acute, administration of CRF itself produced a decreased jcBNST LTP-IE. Thus,
      changes in the intrinsic properties of jcBNST neurons mediated by chronic
      activation of the CRF system may contribute to the persistent emotional
      dysregulation associated with protracted withdrawal.

PMID- 19403811
TI  - Delta-catenin regulates spine and synapse morphogenesis and function in
      hippocampal neurons during development.
AB  - The maintenance of spine and synapse number during development is critical for
      neuronal circuit formation and function. Here we show that delta-catenin, a
      component of the cadherin-catenin cell adhesion complex, regulates spine and
      synapse morphogenesis during development. Genetic ablation or acute knockdown of
      delta-catenin leads to increases in spine and synapse density, accompanied by a
      decrease in tetrodotoxin induced spine plasticity. Our results indicate that
      delta-catenin may mediate conversion of activity-dependent signals to
      morphological spine plasticity. The functional role of delta-catenin in
      regulating spine density does not require binding to cadherins, but does require
      interactions with PDZ domain-containing proteins. We propose that the
      perturbations in spine and synaptic structure and function observed after
      depletion of delta-catenin during development may contribute to functional
      alterations in neural circuitry, the cognitive deficits observed in mutant mice,
      and the mental retardation pathology of Cri-du-chat syndrome.

PMID- 19403813
TI  - Feature-dependent sensitive periods in the development of complex sound
      representation.
AB  - Simple tonal stimuli can shape spectral tuning of cortical neurons during an
      early epoch of brain development. The effects of complex sound experience on
      cortical development remain to be determined. We exposed rat pups to a frequency
      modulated (FM) sweep in different time windows during early development, and
      examined the effects of such sensory experience on sound representations in the
      primary auditory cortex (AI). We found that early exposure to a FM sound resulted
      in altered characteristic frequency representations and broadened spectral tuning
      in AI neurons, whereas later exposure to the same sound only led to greater
      selectivity for the sweep rate and direction of the experienced FM sound. These
      results indicate that cortical representations of different acoustic features are
      shaped by complex sounds in a series of distinct sensitive periods.

PMID- 19403812
TI  - Drosophila Miro is required for both anterograde and retrograde axonal
      mitochondrial transport.
AB  - Microtubule-based transport of mitochondria into dendrites and axons is vital for
      sustaining neuronal function. Transport along microtubule tracks proceeds in a
      series of plus and minus end-directed movements that are facilitated by kinesin
      and dynein motors. How the opposing movements are controlled to achieve effective
      transport over large distances remains unclear. Previous studies showed that the
      conserved mitochondrial GTPase Miro is required for mitochondrial transport into
      axons and dendrites and serves as a Ca(2+) sensor that controls mitochondrial
      mobility. To directly examine Miro's significance for kinesin- and/or dynein
      mediated mitochondrial motility, we live-imaged movements of GFP-tagged
      mitochondria in larval Drosophila motor axons upon genetic manipulations of Miro.
      Loss of Drosophila Miro (dMiro) reduced the effectiveness of both anterograde and
      retrograde mitochondrial transport by selectively impairing kinesin- or dynein
      mediated movements, depending on the direction of net transport. Net
      anterogradely transported mitochondria exhibited reduced kinesin- but normal
      dynein-mediated movements. Net retrogradely transported mitochondria exhibited
      much shorter dynein-mediated movements, whereas kinesin-mediated movements were
      minimally affected. In both cases, the duration of short stationary phases
      increased proportionally. Overexpression (OE) of dMiro also impaired the
      effectiveness of mitochondrial transport. Finally, loss and OE of dMiro altered
      the length of mitochondria in axons through a mechanistically separate pathway.
      We suggest that dMiro promotes effective antero- and retrograde mitochondrial
      transport by extending the processivity of kinesin and dynein motors according to
      a mitochondrion's programmed direction of transport.

PMID- 19403815
TI  - Sensory weighting of force and position feedback in human motor control tasks.
AB  - In daily life humans integrate force and position feedback from mechanoreceptors,
      proprioception, and vision. With handling relatively soft, elastic objects, force
      and position are related and can be integrated to improve the accuracy of an
      estimate of either one. Sensory weighting between different sensory systems
      (e.g., vision and proprioception) has been extensively studied. This study
      investigated whether similar weighting can be found within the proprioceptive
      sensory system, more specifically between the modalities force and position. We
      hypothesized that sensory weighting is governed by object stiffness: position
      feedback is weighted heavier on soft objects (large deflections), while force
      feedback is weighted heavier on stiff objects (small deflections). Subjects were
      instructed to blindly reproduce either position or force while holding a one
      degree of freedom haptic manipulator that simulated a linear spring with one of
      four predetermined stiffnesses. In catch trials the spring was covertly replaced
      by a nonlinear spring. The difference in force (DeltaF) and position (DeltaX)
      between the regular and the catch trials revealed the sensory weighting between
      force and position feedback. A maximum likelihood estimation model predicted
      that: (1) task instruction did not affect the outcome measures, and (2) force
      feedback is weighted heavier with increasing object stiffness as was
      hypothesized. Both effects were found experimentally, and the subjects' sensory
      weighting closely resembled the optimal model predictions. To conclude, this
      study successfully demonstrated sensory weighting within the proprioceptive
      system.

PMID- 19403814
TI  - ABCG2 is upregulated in Alzheimer's brain with cerebral amyloid angiopathy and
      may act as a gatekeeper at the blood-brain barrier for Abeta(1-40) peptides.
AB  - Alzheimer's disease (AD) is characterized by accumulation and deposition of Abeta
      peptides in the brain. Abeta deposition in cerebrovessels occurs in many AD
      patients and results in cerebral amyloid angiopathy (AD/CAA). Since Abeta can be
      transported across blood-brain barrier (BBB), aberrant Abeta trafficking across
      BBB may contribute to Abeta accumulation in the brain and CAA development.
      Expression analyses of 273 BBB-related genes performed in this study showed that
      the drug transporter, ABCG2, was significantly upregulated in the brains of
      AD/CAA compared with age-matched controls. Increased ABCG2 expression was
      confirmed by Q-PCR, Western blot, and immunohistochemistry. Abcg2 was also
      increased in mouse AD models, Tg-SwDI and 3XTg. Abeta alone or in combination
      with hypoxia/ischemia failed to stimulate ABCG2 expression in BBB endothelial
      cells; however, conditioned media from Abeta-activated microglia strongly induced
      ABCG2 expression. ABCG2 protein in AD/CAA brains interacted and
      coimmunoprecipitated with Abeta. Overexpression of hABCG2 reduced drug uptake in
      cells; however, interaction of Abeta(1-40) with ABCG2 impaired ABCG2-mediated
      drug efflux. The role of Abcg2 in Abeta transport at the BBB was investigated in
      Abcg2-null and wild-type mice after intravenous injection of Cy5.5-labeled
      Abeta(1-40) or scrambled Abeta(40-1). Optical imaging analyses of live animals
      and their brains showed that Abcg2-null mice accumulated significantly more Abeta
      in their brains than wild-type mice. The finding was confirmed by
      immunohistochemistry. These results suggest that ABCG2 may act as a gatekeeper at
      the BBB to prevent blood Abeta from entering into brain. ABCG2 upregulation may
      serve as a biomarker of CAA vascular pathology in AD patients.

PMID- 19403816
TI  - Stimulus-specific adaptation in the inferior colliculus of the anesthetized rat.
AB  - To identify sounds as novel, there must be some neural representation of commonly
      occurring sounds. Stimulus-specific adaptation (SSA) is a reduction in neural
      response to a repeated sound. Previous studies using an oddball stimulus paradigm
      have shown that SSA occurs at the cortex, but this study demonstrates that
      neurons in the inferior colliculus (IC) also show strong SSA using this paradigm.
      The majority (66%) of IC neurons showed some degree of SSA. Approximately 18% of
      neurons showed near-complete SSA. Neurons with SSA were found throughout the IC.
      Responses of IC neurons were reduced mainly during the onset component of the
      response, and latency was shorter in response to the oddball stimulus than to the
      standard. Neurons with near-complete SSA were broadly tuned to frequency,
      suggesting a high degree of convergence. Thus, some of the mechanisms that may
      underlie novelty detection and behavioral habituation to common sounds are
      already well developed at the midbrain.

PMID- 19403817
TI  - Neural dynamics in inferior temporal cortex during a visual working memory task.
AB  - Intelligent organisms are capable of tracking objects even when they temporarily
      disappear from sight, a cognitive capacity commonly referred to as visual working
      memory (VWM). The neural basis of VWM has been the subject of significant
      scientific debate, with recent work focusing on the relative roles of posterior
      visual areas, such as the inferior temporal cortex (ITC), and the prefrontal
      cortex. Here we reexamined the contribution of ITC to VWM by recording from
      highly selective individual ITC neurons as monkeys engaged in multiple versions
      of an occlusion-based memory task. As expected, we found strong evidence for a
      role of ITC in stimulus encoding. We also found that almost half of these
      selective cells showed stimulus-selective delay period modulation, with a small
      but significant fraction exhibiting differential responses even in the presence
      of simultaneously visible interfering information. When we combined the
      informational content of multiple neurons, we found that the accuracy with which
      we could decode memory content increased drastically. The memory epoch analyses
      suggest that behaviorally relevant visual memories were reinstated in ITC.
      Furthermore, we observed a population-wide enhancement of neuronal response to a
      match stimulus compared with the same stimulus presented as a nonmatch. The
      single-cell enhancement preceded any match effects identified in the local field
      potential, leading us to speculate that enhancement is the result of neural
      processing local to ITC. Moreover, match enhancement was only later followed by
      the more commonly observed match suppression. Altogether, the data support the
      hypothesis that, when a stimulus is held in memory, ITC neurons are actively
      biased in favor of task-relevant visual representations and that this bias can
      immediately impact subsequent recognition events.

PMID- 19403818
TI  - TrkB signaling is required for both the induction and maintenance of tissue and
      nerve injury-induced persistent pain.
AB  - Activation of primary afferent nociceptors produces acute, short-lived pain, and
      tissue or nerve injury induces long-term enhancement of nociceptive processing,
      manifested as hypersensitivity to thermal and mechanical stimulation. Here we
      used a chemical-genetic and pharmacological approach to study the contribution of
      the receptor tyrosine kinase, type 2 (TrkB) to the generation and maintenance of
      injury-induced persistent pain. We performed the studies in wild-type mice and
      transgenic (TrkB(F616A)) mice that express mutant but fully functional TrkB
      receptors. By injecting a small molecule derivative of the protein kinase
      inhibitor protein phosphatase 1 (1NM-PP1), it is possible to produce highly
      selective inhibition of TrkB autophosphorylation in adult mice, without
      interfering with the activity of other protein kinases. We report that oral
      administration of 1NM-PP1, at doses that blocked phosphorylation of TrkB in the
      spinal cord, had no effect in behavioral tests of acute heat, mechanical, or
      chemical pain sensitivity. However, the same pretreatment with 1NM-PP1 prevented
      the development of tissue- or nerve injury-induced heat and mechanical
      hypersensitivity. Established hypersensitivity was transiently reversed by
      intraperitoneal injection of 1NM-PP1. Although interfering with TrkB signaling
      altered neither acute capsaicin nor formalin-induced pain behavior, the prolonged
      mechanical hypersensitivity produced by these chemical injuries was prevented by
      1NM-PP1 inhibition of TrkB signaling. We conclude that TrkB signaling is not only
      an important contributor to the induction of heat and mechanical hypersensitivity
      produced by tissue or nerve injury but also to the persistence of the pain.

PMID- 19403819
TI  - Monkey prefrontal cortical pyramidal and putative interneurons exhibit
      differential patterns of activity between prosaccade and antisaccade tasks.
AB  - Previous studies have shown that prefrontal cortex (PFC) neurons carry task
      related activity; however, it is largely unknown how this selectivity is
      implemented in PFC microcircuitry. Here, we exploited known differences in
      extracellular action potential waveforms, and antidromic identification, to
      classify PFC neurons as putative pyramidal or interneurons, and investigate their
      relative contributions to task-selectivity. We recorded the activity of
      prefrontal neurons while monkeys performed a blocked pro/antisaccade task in
      which they were required to look either toward or away from a peripheral visual
      stimulus. We found systematic differences in activity between neuron classes.
      Putative pyramidal neurons had higher stimulus-related activity on antisaccade
      trials, whereas putative interneurons exhibited greater activity for prosaccades.
      These findings suggest that task-selectivity in the PFC may be shaped by
      interactions between these neuronal classes. They are also consistent with the
      robust deficits in antisaccade performance frequently observed in disease states
      associated with PFC dysfunction.

PMID- 19403821
TI  - Excitotoxic death of retinal neurons in vivo occurs via a non-cell-autonomous
      mechanism.
AB  - The central hypothesis of excitotoxicity is that excessive stimulation of
      neuronal NMDA-sensitive glutamate receptors is harmful to neurons and contributes
      to a variety of neurological disorders. Glial cells have been proposed to
      participate in excitotoxic neuronal loss, but their precise role is defined
      poorly. In this in vivo study, we show that NMDA induces profound nuclear factor
      kappaB (NF-kappaB) activation in Muller glia but not in retinal neurons.
      Intriguingly, NMDA-induced death of retinal neurons is effectively blocked by
      inhibitors of NF-kappaB activity. We demonstrate that tumor necrosis factor alpha
      (TNFalpha) protein produced in Muller glial cells via an NMDA-induced NF-kappaB
      dependent pathway plays a crucial role in excitotoxic loss of retinal neurons.
      This cell loss occurs mainly through a TNFalpha-dependent increase in Ca(2+)
      permeable AMPA receptors on susceptible neurons. Thus, our data reveal a novel
      non-cell-autonomous mechanism by which glial cells can profoundly exacerbate
      neuronal death following excitotoxic injury.

PMID- 19403820
TI  - Nicotinamide mononucleotide adenylyl transferase-mediated axonal protection
      requires enzymatic activity but not increased levels of neuronal nicotinamide
      adenine dinucleotide.
AB  - Axonal degeneration is a hallmark of many neurological disorders. Studies in
      animal models of neurodegenerative diseases indicate that axonal degeneration is
      an early event in the disease process, and delaying this process can lead to
      decreased progression of the disease and survival extension. Overexpression of
      the Wallerian degeneration slow (Wld(s)) protein can delay axonal degeneration
      initiated via axotomy, chemotherapeutic agents, or genetic mutations. The Wld(s)
      protein consists of the N-terminal portion of the ubiquitination factor Ube4b
      fused to the nicotinamide adenine dinucleotide (NAD(+)) biosynthetic enzyme
      nicotinamide mononucleotide adenylyl transferase 1 (Nmnat1). We previously showed
      that the Nmnat1 portion of this fusion protein was the critical moiety for Wld(s)
      mediated axonal protection. Here, we describe the development of an automated
      quantitative assay for assessing axonal degeneration. This method successfully
      showed that Nmnat1 enzymatic activity is important for axonal protection as
      mutants with reduced enzymatic activity lacked axon protective activity. We also
      found that Nmnat enzymes with diverse sequences and structures from various
      species, including Drosophila melanogaster, Saccharomyces cerevisiae, and
      archaebacterium Methanocaldococcus jannaschii, which encodes a protein with no
      homology to eukaryotic Nmnat enzymes, all mediate robust axonal protection after
      axotomy. Besides the importance of Nmnat enzymatic activity, we did not observe
      changes in the steady-state NAD(+) level, and we found that inhibition of
      nicotinamide phosphoribosyltransferase (Nampt), which synthesizes substrate for
      Nmnat in mammalian cells, did not affect the protective activity of Nmnat1. These
      results provide the possibility of a role for new Nmnat enzymatic activity in
      axonal protection in addition to NAD(+) synthesis.

PMID- 19403822
TI  - Alpha9 integrin promotes neurite outgrowth on tenascin-C and enhances sensory
      axon regeneration.
AB  - Damaged CNS axons are prevented from regenerating by an environment containing
      many inhibitory factors. They also lack an integrin that interacts with tenascin
      C, the main extracellular matrix glycoprotein of the CNS, which is upregulated
      after injury. The alpha9beta1 integrin heterodimer is a receptor for the
      nonalternatively spliced region of tenascin-C, but the alpha9 subunit is absent
      in adult neurons. In this study, we show that PC12 cells and adult rat dorsal
      root ganglion (DRG) neurons do not extend neurites on tenascin-C. However, after
      forced expression of alpha9 integrin, extensive neurite outgrowth from PC12 cells
      and adult rat DRG neurons occurs. Moreover, both DRG neurons and PC12 cells
      secrete tenascin-C, enabling alpha9-transfected cells to grow axons on tissue
      culture plastic. Using adeno-associated viruses to express alpha9 integrin in
      vivo in DRGs, we examined axonal regeneration after cervical dorsal rhizotomy or
      dorsal column crush in the adult rat. After rhizotomy, significantly more dorsal
      root axons regrew into the dorsal root entry zone at 6 weeks after injury in
      alpha9 integrin-expressing animals than in green fluorescent protein (GFP)
      controls. Similarly, after a dorsal column crush injury, there was significantly
      more axonal growth into the lesion site compared with GFP controls at 6 weeks
      after injury. Behavioral analysis after spinal cord injury revealed that both
      experimental and control groups had an increased withdrawal latency in response
      to mechanical stimulation when compared with sham controls; however, in response
      to heat stimulation, normal withdrawal latencies returned after alpha9 integrin
      treatment but remained elevated in control groups.

PMID- 19403823
TI  - The translational repressors Nanos and Pumilio have divergent effects on
      presynaptic terminal growth and postsynaptic glutamate receptor subunit
      composition.
AB  - Pumilio (Pum) is a translational repressor that binds selectively to target mRNAs
      and recruits Nanos (Nos) as a corepressor. In the larval neuromuscular system,
      Pum represses expression of the translation factor eIF-4E and the glutamate
      receptor subunit GluRIIA. Here, we show that Nos, like Pum, is expressed at the
      neuromuscular junction (NMJ) and in neuronal cell bodies. Surprisingly, however,
      Nos and Pum have divergent functions on both the presynaptic and postsynaptic
      sides of the NMJ. In nos mutant and nos RNA interference larvae, the number of
      NMJ boutons is increased, whereas loss of Pum reduces the bouton number. On the
      postsynaptic side, Nos acts in opposition to Pum in regulating the subunit
      composition of the glutamate receptor. NMJ active zones are associated with
      GluRIIA- and GluRIIB-containing receptor clusters. Loss of Nos causes
      downregulation of GluRIIA and increases the levels of GluRIIB. Consistent with
      this finding, the electrophysiological properties of NMJs lacking postsynaptic
      Nos suggest that they use primarily GluRIIB-containing receptors. Nos can
      regulate GluRIIB in the absence of GluRIIA, suggesting that the effects of Nos on
      GluRIIB levels are at least partially independent of synaptic competition between
      GluRIIA and GluRIIB. Nos is a target for Pum repression, and Pum binds
      selectively to the 3' untranslated regions of the nos and GluRIIA mRNAs. Our
      results suggest a model in which regulatory interplay among Pum, Nos, GluRIIA,
      and GluRIIB could cause a small change in Pum activity to be amplified into a
      large shift in the balance between GluRIIA and GluRIIB synapses.

PMID- 19403825
TI  - Activity pattern-dependent long-term potentiation in neocortex and hippocampus of
      GluA1 (GluR-A) subunit-deficient mice.
AB  - The AMPA receptor subunit GluA1 (GluR-A) has been implicated to be critically
      involved in the expression of long-term potentiation (LTP) and memory formation.
      Mice lacking this subunit possess a profound spatial working memory deficit. We
      investigated the influence of the GluA1 subunit on the expression of LTP in
      pyramidal neurons of the hippocampus CA1 region and somatosensory cortex layer
      2/3 for different cellular LTP protocols in adult mice. We found that the GluA1
      subunit was not required for LTP in cortical pyramidal neurons. In contrast,
      GluA1-dependent LTP expression in CA1 pyramidal neurons was differentially
      dependent on the LTP induction parameters. Depolarization pairing was
      exclusively, theta-burst pairing was partially, and spike-timing-dependent
      plasticity (STDP) was independent of the GluA1 subunit. Spike-timing-dependent
      LTP required postsynaptic membrane fusion in CA1 pyramidal neurons. We conclude
      that during LTP induction at the hippocampal CA3-to-CA1 synapse the recruitment
      of the GluA1 subunit is controlled by particular electrical activity patterns
      that might reflect specific behavioral states. Furthermore, other LTP expression
      mechanisms exist that do not require the presence of GluA1. The previously
      reported spatial working memory deficits in GluA1-lacking mice (Gria1(-/-) mice)
      together with these results suggest that STDP might be a likely basis for the
      formation of spatial reference memory whereas it is not required for the rapid
      formation of spatial working memory where a fast but transient increase of
      synaptic efficacy might be needed.

PMID- 19403824
TI  - How multiple conductances determine electrophysiological properties in a
      multicompartment model.
AB  - Most neurons have large numbers of voltage- and time-dependent currents that
      contribute to their electrical firing patterns. Because these currents are
      nonlinear, it can be difficult to determine the role each current plays in
      determining how a neuron fires. The lateral pyloric (LP) neuron of the
      stomatogastric ganglion of decapod crustaceans has been studied extensively
      biophysically. We constructed approximately 600,000 versions of a four
      compartment model of the LP neuron and distributed 11 different currents into the
      compartments. From these, we selected approximately 1300 models that match well
      the electrophysiological properties of the biological neuron. Interestingly,
      correlations that were seen in the expression of channel mRNA in biological
      studies were not found across the approximately 1300 admissible LP neuron models,
      suggesting that the electrical phenotype does not require these correlations. We
      used cubic fits of the function from maximal conductances to a series of
      electrophysiological properties to ask which conductances predominantly influence
      input conductance, resting membrane potential, resting spike rate, phasing of
      activity in response to rhythmic inhibition, and several other properties. In all
      cases, multiple conductances contribute to the measured property, and the
      combinations of currents that strongly influence each property differ. These
      methods can be used to understand how multiple currents in any candidate neuron
      interact to determine the cell's electrophysiological behavior.

PMID- 19403826
TI  - Homeostatic and nonhomeostatic modulation of learning in human motor cortex.
AB  - Motor learning is important throughout life for acquisition and adjustment of
      motor skill. The extent of motor learning may be modulated by the history of
      motor cortex activity, but little is known which metaplasticity rule (homeostatic
      vs nonhomeostatic) governs this interaction. Here, we explored in nine healthy
      adults the effects of three different paired associative stimulation (PAS)
      protocols on subsequent learning of rapid thumb flexion movements. PAS resulted
      in either a long-term potentiation (LTP)-like increase in excitability of the
      stimulated motor cortex (PAS(LTP)), or a long-term depression (LTD)-like decrease
      (PAS(LTD)), or no change (control condition, PAS(CON)). Learning was indexed by
      the increase in peak acceleration of the trained movement. Delays of 0 and 90 min
      between PAS and motor practice were tested. At the 0 min delay, PAS(LTD) strongly
      facilitated motor learning (homeostatic interaction), and PAS(LTP) also
      facilitated learning, although to a lesser extent (nonhomeostatic interaction).
      At the 90 min delay, PAS(LTD) facilitated learning, whereas PAS(LTP) depressed
      learning (interactions both homeostatic). Therefore, facilitation of learning by
      previous brain stimulation occurs primarily and most effectively through
      homeostatic interactions, but at the 0 min delay, nonhomeostatic mechanisms such
      as LTP-induced blockade of LTD and nonsaturated LTP-induced facilitation of
      learning might also play a role. The present findings demonstrate that motor
      learning in humans can be modulated by noninvasive brain stimulation and suggest
      the possibility of enhancing motor relearning in defined neurological patients.

PMID- 19403827
TI  - Persistent transcription- and translation-dependent long-term potentiation
      induced by mGluR1 in hippocampal interneurons.
AB  - Hippocampal interneurons synchronize the activity of large neuronal ensembles
      during memory consolidation. Although the latter process is manifested as
      increases in synaptic efficacy which require new protein synthesis in pyramidal
      neurons, it is unknown whether such enduring plasticity occurs in interneurons.
      Here, we uncover a long-term potentiation (LTP) of transmission at individual
      interneuron excitatory synapses which persists for at least 24 h, after
      repetitive activation of type-1 metabotropic glutamate receptors [mGluR1-mediated
      chemical late LTP (cL-LTP(mGluR1))]. cL-LTP(mGluR1) involves presynaptic and
      postsynaptic expression mechanisms and requires both transcription and
      translation via phosphoinositide 3-kinase/mammalian target of rapamycin and MAP
      kinase kinase-extracellular signal-regulated protein kinase signaling pathways.
      Moreover, cL-LTP(mGluR1) involves translational control at the level of
      initiation as it is prevented by hippuristanol, an inhibitor of eIF4A, and
      facilitated in mice lacking the cap-dependent translational repressor, 4E-BP. Our
      results reveal novel mechanisms of long-term synaptic plasticity that are
      transcription and translation-dependent in inhibitory interneurons, indicating
      that persistent synaptic modifications in interneuron circuits may contribute to
      hippocampal-dependent cognitive processes.

PMID- 19403830
TI  - Multitasking of attention and memory functions in the primate prefrontal cortex.
AB  - In motor and sensory areas of cortex, neuronal activity often depends on the
      location of a movement target or a sensory stimulus, with each neuron tuned to a
      single part of space called a preferred direction (when motor) or a receptive
      field (when sensory). As we previously reported, some neurons in the monkey
      prefrontal cortex are tuned to two parts of space, which we interpreted as
      reflecting attention and working memory, respectively. Monkeys performed a
      behavioral task in which they attended to a visual stimulus at one location while
      remembering a second place, and these locations were varied from trial to trial
      to assess spatial tuning. Most spatially tuned neurons specialized in either
      attentional or mnemonic processing, but about one-third of the cells showed
      tuning for both. Here, we show that the latter population, called multitasking
      neurons, improves the encoding of both the attended and remembered locations.
      These neurons do so for three reasons: (1) the preferred directions for attention
      and for working memory usually differ (and often diametrically oppose one
      another), (2) they have stronger tuning than specialized cells, and (3) pairs of
      multitasking neurons represent these cognitive parameters more efficiently than
      pairs that include even a single specialized cell. These findings suggest that
      multitasking neurons provide a computational advantage for behaviors that place
      simultaneous demands on two or more cognitive processes.

PMID- 19403828
TI  - Differential regulation of gonadotropin-releasing hormone neuron activity and
      membrane properties by acutely applied estradiol: dependence on dose and estrogen
      receptor subtype.
AB  - Gonadotropin-releasing hormone (GnRH) neurons are critical to controlling
      fertility. In vivo, estradiol can inhibit or stimulate GnRH release depending on
      concentration and physiological state. We examined rapid, nongenomic effects of
      estradiol. Whole-cell recordings were made of GnRH neurons in brain slices from
      ovariectomized mice with ionotropic GABA and glutamate receptors blocked.
      Estradiol was bath applied and measurements completed within 15 min. Estradiol
      from high physiological (preovulatory) concentrations (100 pm) to 100 nm enhanced
      action potential firing, reduced afterhyperpolarizing potential (AHP) and
      increased slow afterdepolarization amplitudes (ADP), and reduced I(AHP) and
      enhanced I(ADP). The reduction of I(AHP) was occluded by previous blockade of
      calcium-activated potassium channels. These effects were mimicked by an estrogen
      receptor (ER) beta-specific agonist and were blocked by the classical receptor
      antagonist ICI182780. ERalpha or GPR30 agonists had no effect. The acute
      stimulatory effect of high physiological estradiol on firing rate was dependent
      on signaling via protein kinase A. In contrast, low physiological levels of
      estradiol (10 pm) did not affect intrinsic properties. Without blockade of
      ionotropic GABA and glutamate receptors, however, 10 pm estradiol reduced firing
      of GnRH neurons; this was mimicked by an ERalpha agonist. ERalpha agonists
      reduced the frequency of GABA transmission to GnRH neurons; GABA can excite to
      these cells. In contrast, ERbeta agonists increased GABA transmission and
      postsynaptic response. These data suggest rapid intrinsic and network modulation
      of GnRH neurons by estradiol is dependent on both dose and receptor subtype. In
      cooperation with genomic actions, nongenomic effects may play a role in feedback
      regulation of GnRH secretion.

PMID- 19403829
TI  - Importin 13 regulates neurotransmitter release at the Drosophila neuromuscular
      junction.
AB  - In an unbiased genetic screen designed to isolate mutations that affect synaptic
      transmission, we have isolated homozygous lethal mutations in Drosophila importin
      13 (imp13). Imp13 is expressed in and around nuclei of both neurons and muscles.
      At the larval neuromuscular junction (NMJ), imp13 affects muscle growth and
      formation of the subsynaptic reticulum without influencing any presynaptic
      structural features. In the absence of imp13, the probability of release of
      neurotransmitter and quantal content is increased, yet the abundance of the
      postsynaptic receptors and the amplitude of miniature excitatory junctional
      potentials are not affected. Interestingly, imp13 is required in the muscles to
      control presynaptic release. Thus, imp13 is a novel factor that affects
      neurotransmitter release at the fly NMJ. Its role in the context of synaptic
      homeostasis is discussed.

PMID- 19403831
TI  - The N-terminal domain of Slack determines the formation and trafficking of
      Slick/Slack heteromeric sodium-activated potassium channels.
AB  - Potassium channels activated by intracellular Na(+) ions (K(Na)) play several
      distinct roles in regulating the firing patterns of neurons, and, at the single
      channel level, their properties are quite diverse. Two known genes, Slick and
      Slack, encode K(Na) channels. We have now found that Slick and Slack subunits
      coassemble to form heteromeric channels that differ from the homomers in their
      unitary conductance, kinetic behavior, subcellular localization, and response to
      activation of protein kinase C. Heteromer formation requires the N-terminal
      domain of Slack-B, one of the alternative splice variants of the Slack channel.
      This cytoplasmic N-terminal domain of Slack-B also facilitates the localization
      of heteromeric K(Na) channels to the plasma membrane. Immunocytochemical studies
      indicate that Slick and Slack-B subunits are coexpressed in many central neurons.
      Our findings provide a molecular explanation for some of the diversity in
      reported properties of neuronal K(Na) channels.

PMID- 19403832
TI  - AbetaPP/APLP2 family of Kunitz serine proteinase inhibitors regulate cerebral
      thrombosis.
AB  - The amyloid beta-protein precursor (AbetaPP) is best recognized as the precursor
      to the Abeta peptide that accumulates in the brains of patients with Alzheimer's
      disease, but less is known about its physiological functions. Isoforms of AbetaPP
      that contain a Kunitz-type serine proteinase inhibitor (KPI) domain are expressed
      in brain and, outside the CNS, in circulating blood platelets. Recently, we
      showed that KPI-containing forms of AbetaPP regulates cerebral thrombosis in vivo
      (Xu et al., 2005, 2007). Amyloid precursor like protein-2 (APLP2), a closely
      related homolog to AbetaPP, also possesses a highly conserved KPI domain.
      Virtually nothing is known of its function. Here, we show that APLP2 also
      regulates cerebral thrombosis risk. Recombinant purified KPI domains of AbetaPP
      and APLP2 both inhibit the plasma clotting in vitro. In a carotid artery
      thrombosis model, both AbetaPP(-/-) and APLP2(-/-) mice exhibit similar
      significantly shorter times to vessel occlusion compared with wild-type mice
      indicating a prothrombotic phenotype. Similarly, in an experimental model of
      intracerebral hemorrhage, both AbetaPP(-/-) and APLP2(-/-) mice produce
      significantly smaller hematomas with reduced brain hemoglobin content compared
      with wild-type mice. Together, these results indicate that AbetaPP and APLP2
      share overlapping anticoagulant functions with regard to regulating thrombosis
      after cerebral vascular injury.

PMID- 19403833
TI  - Distinct encoding of spatial and nonspatial visual information in parietal
      cortex.
AB  - It is well established that the primate parietal cortex plays an important role
      in visuospatial processing. Parietal cortex damage in both humans and monkeys can
      lead to behavioral deficits in spatial processing, and many parietal neurons,
      such as in the macaque lateral intraparietal area (LIP), are strongly influenced
      by visual-spatial factors. Several recent studies have shown that LIP neurons can
      also convey robust signals related to nonspatial factors, such as color, shape,
      and the behavioral context or rule that is relevant for solving the task at hand.
      But what is the relationship between the encoding of spatial factors and more
      abstract, nonspatial, influences in LIP? To examine this, we trained monkeys to
      group visual motion patterns into two arbitrary categories, and recorded the
      activity of LIP neurons while monkeys performed a categorization task in which
      stimuli were presented either inside each neuron's receptive field (RF) or at a
      location in the opposite visual field. While the activity of nearly all LIP
      neurons showed strong spatial dependence (i.e., greater responses when stimuli
      were presented within neurons' RFs), we also found that many LIP neurons also
      showed reliable encoding of the category membership of stimuli even when the
      stimuli were presented away from neurons' RFs. This suggests that both spatial
      and nonspatial information can be encoded by individual LIP neurons, and that
      parietal cortex may be a nexus for the integration of visuospatial signals and
      more abstract task-dependent information during complex visually based behaviors.

PMID- 19403835
TI  - SRC family kinases are required for limb trajectory selection by spinal motor
      axons.
AB  - Signal relay by guidance receptors at the axonal growth cone is a process
      essential for the assembly of a functional nervous system. We investigated the in
      vivo function of Src family kinases (SFKs) as growth cone guidance signaling
      intermediates in the context of spinal lateral motor column (LMC) motor axon
      projection toward the ventral or dorsal limb mesenchyme. Using in situ mRNA
      detection we determined that Src and Fyn are expressed in LMC motor neurons of
      chick and mouse embryos at the time of limb trajectory selection. Inhibition of
      SFK activity by C-terminal Src kinase (Csk) overexpression in chick LMC axons
      using in ovo electroporation resulted in LMC axons selecting the inappropriate
      dorsoventral trajectory within the limb mesenchyme, with medial LMC axon
      projecting into the dorsal and ventral limb nerve with apparently random
      incidence. We also detected LMC axon trajectory choice errors in Src mutant mice
      demonstrating a nonredundant role for Src in motor axon guidance in agreement
      with gain and loss of Src function in chick LMC neurons which led to the
      redirection of LMC axons. Finally, Csk-mediated SFK inhibition attenuated the
      retargeting of LMC axons caused by EphA or EphB over-expression, implying the
      participation of SFKs in Eph-mediated LMC motor axon guidance. In summary, our
      findings demonstrate that SFKs are essential for motor axon guidance and suggest
      that they play an important role in relaying ephrin:Eph signals that mediate the
      selection of motor axon trajectory in the limb.

PMID- 19403834
TI  - Propriospinal bypass of the serotonergic system that can facilitate stepping.
AB  - The neurotransmitter systems mediating spinal locomotion in response to epidural
      spinal cord stimulation (ES) have not been identified. Here, we examine the role
      of the serotonergic system in regulating locomotor behavior of decerebrated cats
      during ES at L4-L5. ES elicited coordinated, weight-bearing, hindlimb stepping
      with plantar foot placement on a moving treadmill belt. Ketanserin [a 5
      hydroxytryptamine (serotonin) (5-HT)(2/7) receptor antagonist] depressed this
      locomotor activity: only weak rhythmic movements without plantar foot placement
      and depressed EMG activity were observed. Cyproheptadine, a nonselective 5-HT
      blocker, prevented facilitation of stepping by epidural stimulation. These data
      demonstrate an important role of the serotonergic system in facilitating
      locomotion in the presence of epidural stimulation. In the presence of
      ketanserin, passive movements of one forelimb in a step-like manner immediately
      induced stepping of both hindlimbs with EMG patterns similar to those observed
      with ES without ketanserin. Thus, a non-5-HT-dependent spinal circuitry
      projecting from the cervical to the lumbar region of the spinal cord can
      facilitate stepping. The specific neurotransmitters responsible for this forelimb
      facilitated stepping of the hindlimbs are unknown. These data suggest that a 5
      HT(2/7) receptor-dependent pathway that processes hindlimb locomotor-like
      proprioception to facilitate hindlimb stepping can be complemented with
      proprioceptive afferents from the forelimbs via a non-5-HT(2/7) receptor
      neurotransmitter system. Thus, different neurotransmitter receptor systems can be
      used to mediate the same type of sensory event, i.e., locomotor-like
      proprioception to facilitate the same motor task, i.e., hindlimb stepping.

PMID- 19403837
TI  - Comparative evaluation of the measurement properties of various shoulder outcome
      instruments.
AB  - BACKGROUND: Various shoulder outcome instruments have been used despite lack of
      information on their measurement properties; reliability, responsiveness, and
      validity; and correlation with health-related quality of life. HYPOTHESIS: Most
      shoulder outcome instruments have poor correlation with Short Form-36, a general
      measure of health-related quality of life, and with each other. STUDY DESIGN:
      Cohort study (diagnosis); Level of evidence, 2. METHODS: A consecutive group of
      285 patients who had undergone shoulder surgery completed several shoulder
      outcome instruments-Short Form-36; University of California, Los Angeles shoulder
      score; American Shoulder and Elbow Surgeons shoulder evaluation form; Constant
      score; Simple Shoulder Test; Western Ontario Shoulder Instability Index; and the
      rating sheet for Bankart repair (Rowe score)-preoperatively and at 3, 6, 9, and
      12 months postoperatively. Internal consistency, standardized response mean,
      effect size, and Pearson correlation were used to evaluate reliability,
      responsiveness, and validity. RESULTS: The American Shoulder and Elbow Surgeons
      form, Simple Shoulder Test, and Western Ontario Shoulder Instability Index
      displayed good internal consistency. The University of California, Los Angeles
      shoulder score and American Shoulder and Elbow Surgeons form exhibited good
      responsiveness, whereas Short Form-36 showed the least responsiveness. Pearson
      correlation coefficients between the shoulder outcome instruments and Short Form
      36 were less than excellent (r < .60). Pearson correlation coefficients between
      the outcome instruments were generally low except for the Constant score and
      University of California, Los Angeles shoulder score (r = .673, P < .01).
      CONCLUSION: There was no single shoulder outcome instrument that was superior to
      the others in terms of the measurement properties. Most of the tested shoulder
      outcome instruments did not reflect health-related quality of life well and
      poorly correlated with each other. This meant that the comparison of a given
      surgical result with different outcome instruments might be of little practical
      utility. Further prospective and serial studies should be conducted to develop
      better shoulder outcome instruments that have significant reliability,
      responsiveness, validity, and correlation with health-related quality of life. A
      careful combination of outcome instruments might be necessary to compensate the
      current evaluation systems.

PMID- 19403838
TI  - Iatrogenic severe depression of high-density lipoprotein cholesterol.
AB  - The authors present 5 cases of paradoxical depression of high-density lipoprotein
      (HDL) cholesterol induced by fibrate drugs. In a 24-month review of all cases
      seen in one physician's practice at the Winnipeg Health Sciences Centre Lipid
      Clinic, 492 patients made a total of 1187 visits. Sixty-eight of them were given
      a fibrate drug (14%). Ten patients had HDL cholesterol levels that were less than
      0.5 mmol/L (2%), and of these, 5 cases were due to exposure to fenofibrate (1%).
      These 5 cases comprised 7.4% of the 68 patients who were given any fibrate drug
      during that period. Mean levels were as follows: HDL cholesterol on fenofibrate
      0.27, off fenofibrate 1.0 mmol/L and apo A1 on fenofibrate 0.41, off fenofibrate
      1.17 g/L. A literature review revealed documented cases in 37 patients involving
      fibrates alone or in combination with other drugs known to cause decreased HDL
      cholesterol levels. In 13 patients, exposure was to fibrate therapy alone; in
      those exposed to combinations, the effect was clearly attributable to fibrates in
      9; in 14, the nonfibrates (mostly rosiglitazone) were the attributable drugs; and
      in 1, it was impossible to tell. Thus, fibrate therapy should always be suspected
      as a cause of profoundly depressed HDL cholesterol.

PMID- 19403836
TI  - Short-latency visual input to the subthalamic nucleus is provided by the midbrain
      superior colliculus.
AB  - The subthalamic nucleus (STN) is one of the principal input nuclei of the basal
      ganglia. Using electrophysiological techniques in anesthetized rats, we show that
      the STN becomes responsive to visual stimuli at short latencies when local
      disinhibitory injections are made into the midbrain superior colliculus (SC), an
      important subcortical visual structure. Significantly, only injections into the
      lateral, but not medial, deep layers of the SC were effective. Corresponding
      disinhibition of primary visual cortex also was ineffective. Complementary
      anatomical analyses revealed a strong, regionally specific projection from the
      deep layers of the lateral SC to neurons in rostral and dorsal sectors of the
      STN. Given the retinocentric organization of the SC, these results suggest that
      lower-field stimuli represented in the lateral colliculus have a direct means of
      communicating with the basal ganglia via the STN that is not afforded to visual
      events occurring in the upper visual field.

PMID- 19403839
TI  - Vibrotactile perception and effects of short-term exposure to hand-arm vibration.
AB  - This study clarifies whether the established frequency weighting procedure for
      evaluating exposure to hand-transmitted vibration can effectively evaluate the
      temporary changes in vibrotactile perception thresholds due to pre-exposure to
      vibration. In addition, this study investigates the relationship between changes
      of the vibrotactile perception thresholds and the normalized energy-equivalent
      frequency-weighted acceleration. The fingers of 10 healthy subjects, five male
      and five female, were exposed to vibration under 16 conditions with a combination
      of different frequencies, intensities, and exposure times. The vibration
      frequencies were 31.5 and 125 Hz and exposure lasted between 2 and 16 min.
      According to International Organization for Standardization (ISO) 5349-1, the
      energy-equivalent frequency-weighted acceleration for the experimental time of 16
      min is 2.5 or 5.0 m s(-2) root-mean-square, corresponding to a 8-h equivalent
      acceleration, A(8), of approximately 0.5 and 0.9 m s(-2), respectively. A measure
      of the vibrotactile perception thresholds was conducted before the different
      exposures to vibration. Immediately after the vibration exposure, the acute
      effect was measured continuously on the exposed index finger for the first 75 s,
      followed by 30 s of measures every minute for a maximum of 10 min. If the
      subject's thresholds had not recovered, the measures continued for a maximum of
      30 min with measurements taken every 5 min. Pre-exposure to vibration
      significantly influenced vibrotactile thresholds. This study concludes that the
      influence on the thresholds depends on the frequency of the vibration stimuli.
      Increased equivalent frequency-weighted acceleration resulted in a significant
      change in threshold, but the thresholds were unaffected when changes in the
      vibration magnitude were expressed as the frequency-weighted acceleration or the
      unweighted acceleration. Moreover, the frequency of the pre-vibration exposure
      significantly influenced (up to 25 min after exposure) recovery time of the
      vibrotactile thresholds. This study shows that the frequency weighting procedure
      in ISO 5349-1 is unable to predict the produced acute changes in the vibrotactile
      perception. Moreover, the results imply that the calculation of the 'energy
      equivalent' frequency-weighted acceleration does not reflect the acute changes of
      the vibration perception thresholds due to pre-exposure to vibration.
      Furthermore, when testing for the vibrotactile thresholds, exposure to vibration
      on the day of a test might influence the results. Until further knowledge is
      obtained, the previous practice of 3 h avoidance of vibration exposure before
      assessment is recommended.

PMID- 19403840
TI  - Bayesian modeling of exposure and airflow using two-zone models.
AB  - Mathematical modeling is being increasingly used as a means for assessing
      occupational exposures. However, predicting exposure in real settings is
      constrained by lack of quantitative knowledge of exposure determinants.
      Validation of models in occupational settings is, therefore, a challenge. Not
      only do the model parameters need to be known, the models also need to predict
      the output with some degree of accuracy. In this paper, a Bayesian statistical
      framework is used for estimating model parameters and exposure concentrations for
      a two-zone model. The model predicts concentrations in a zone near the source and
      far away from the source as functions of the toluene generation rate, air
      ventilation rate through the chamber, and the airflow between near and far
      fields. The framework combines prior or expert information on the physical model
      along with the observed data. The framework is applied to simulated data as well
      as data obtained from the experiments conducted in a chamber. Toluene vapors are
      generated from a source under different conditions of airflow direction, the
      presence of a mannequin, and simulated body heat of the mannequin. The Bayesian
      framework accounts for uncertainty in measurement as well as in the unknown rate
      of airflow between the near and far fields. The results show that estimates of
      the interzonal airflow are always close to the estimated equilibrium solutions,
      which implies that the method works efficiently. The predictions of near-field
      concentration for both the simulated and real data show nice concordance with the
      true values, indicating that the two-zone model assumptions agree with the
      reality to a large extent and the model is suitable for predicting the
      contaminant concentration. Comparison of the estimated model and its margin of
      error with the experimental data thus enables validation of the physical model
      assumptions. The approach illustrates how exposure models and information on
      model parameters together with the knowledge of uncertainty and variability in
      these quantities can be used to not only provide better estimates of model
      outputs but also model parameters.

PMID- 19403841
TI  - Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk.
AB  - It was suggested that vitamin D levels influence cancer development. The vitamin
      D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D.
      Results from previous studies on the association of VDR polymorphisms with
      different cancer types are somewhat contradictory, and the role of VDR in the
      etiology of cancer is still equivocal. We therefore performed a meta-analysis on
      the association between the two most studied VDR polymorphisms (FokI and BsmI)
      and any cancer site. Up to January 2009, we identified 67 independent studies. We
      used random-effects models to provide summary odds ratio (SOR) for VDR
      polymorphisms and cancer. We tested homogeneity of effects across studies and
      publication bias and explored between-study heterogeneity. When comparing FokI ff
      with FF carriers, we found a significant increase in skin cancer [SOR; 95%
      confidence intervals (CIs): 1.30; 1.04-1.61] and breast cancer (SOR; 95%CI: 1.14;
      1.03-1.27) risk. For the same genotype comparison, we found a significantly
      higher risk of cancer when we pooled estimates from cancer sites possibly
      associated with vitamin D levels (prostate, breast, skin, ovary, non-Hodgkin
      lymphoma and colorectal). A significant reduction in prostate cancer risk was
      observed for carriers of BsmI Bb compared with bb genotype (SOR; 95%CI: 0.83;
      0.69-0.99). In Caucasian populations, both Bb and BB carriers had a significant
      reduced risk of cancer at any site. In conclusion, this meta-analysis showed that
      VDR FokI and BsmI polymorphisms might modulate the risk of cancer of breast, skin
      and prostate and possibly affect cancer risk at any site in Caucasians.

PMID- 19403842
TI  - Height and site-specific cancer risk: A cohort study of a korean adult
      population.
AB  - To evaluate the association between height and risk of cancer in an East Asian,
      middle-income population, the authors followed up a cohort of 788,789 Koreans
      (449,214 men and 339,575 women) aged 40-64 years for cancer incidence between
      1994 and 2003. Cox proportional hazards regression analysis was used to evaluate
      the association. Each 5-cm increment in height was associated with 5% and 7%
      higher risk of all-sites cancer in men and women, respectively, after adjustment
      for age, body mass index, and behavioral and socioeconomic factors. When the
      associations were evaluated for site-specific cancers, a positive association was
      observed for cancer of the colon and thyroid in both men and women. Among gender
      specific cancers, prostate cancer was positively associated with height in men.
      In women, there was a positive association between height and cancers of the
      breast and ovary, which did not change even after additional adjustment for
      reproductive factors. Although more clarification is needed for some site
      specific cancers, the same positive association of height with cancer in a middle
      income Korean population as found in high-income Western populations supports the
      influence of early life environment on cancer development in adulthood.

PMID- 19403843
TI  - Exposure to farm crops, livestock, and farm tasks and risk of glioma: the Upper
      Midwest Health Study.
AB  - Some studies of brain cancer have found an excess risk for farmers. The National
      Institute for Occupational Safety and Health previously found no increased glioma
      risk for ever (vs. never) being exposed to pesticides on a farm among 798 cases
      and 1,175 population-based controls (adult (ages 18-80 years) nonmetropolitan
      residents of Iowa, Michigan, Minnesota, and Wisconsin). For this analysis (1995
      1998), 288 cases and 474 controls (or their proxies) who had lived on farms at
      age 18 years or after were asked about exposure to crops, livestock, and farm
      tasks. Logistic regression was used to calculate odds ratios adjusted for age,
      age group, sex, state, and education. Never immediately washing up (adjusted odds
      ratio (OR) = 3.08, 95% confidence interval (CI): 1.78, 5.34) or changing clothes
      (OR = 2.84, 95% CI: 1.04, 7.78) after applying pesticides was associated with
      increased glioma risk. Living on a farm on which corn, oats, soybeans, or hogs
      were raised was associated with decreased risk (corn-OR = 0.37, 95% CI: 0.20,
      0.69; oats-OR = 0.63, 95% CI: 0.40, 1.00; soybeans-OR = 0.69, 95% CI: 0.48, 0.98;
      hogs-OR = 0.63, 95% CI: 0.43, 0.93). Negative associations may be due to chance
      or a "healthy farmer" effect. Farmers' increased risk of glioma may be due to
      work practices, other activities, or an inverse association with allergies
      (reported by other investigators).

PMID- 19403844
TI  - Time-varying effects of prognostic factors associated with disease-free survival
      in breast cancer.
AB  - Early detection and effective treatments have dramatically improved breast cancer
      survivorship, yet the risk of relapse persists even 15 years after the initial
      diagnosis. It is important to identify prognostic factors for late breast cancer
      events. The authors investigated time-varying effects of tumor characteristics on
      breast-cancer-free survival using data on 3,088 breast cancer survivors from 4 US
      states who participated in a randomized dietary intervention trial in 1995-2006,
      with maximum follow-up through 15 years (median, 9 years). A piecewise constant
      penalized spline approach incorporating time-varying coefficients was adopted,
      allowing for deviations from the proportional hazards assumption. This method is
      more flexible than standard approaches, provides direct estimates of hazard
      ratios across time intervals, and is computationally tractable. Having a stage II
      or III tumor was associated with a 3-fold higher hazard of breast cancer than
      having a stage I tumor during the first 2.5 years after diagnosis; this hazard
      ratio decreased to 2.1 after 7.7 years, but higher tumor stage remained a
      significant risk factor. Similar diminishing effects were found for poorly
      differentiated tumors. Interestingly, having a positive estrogen receptor status
      was protective up to 4 years after diagnosis but detrimental after 7.7 years
      (hazard ratio = 1.5). These results emphasize the importance of careful
      statistical modeling allowing for possibly time-dependent effects in long-term
      survivorship studies.

PMID- 19403846
TI  - Increased radiation dose to overweight and obese patients from radiographic
      examinations.
AB  - PURPOSE: To estimate the increase in effective radiation dose from diagnostic x
      rays for overweight and obese adult patients, as compared with the effective dose
      for lean reference phantoms. MATERIALS AND METHODS: Relative effective radiation
      doses (E/E(0)) for the acquisition of chest and abdominal radiographs were
      calculated by using Monte Carlo computer simulations of effective doses delivered
      to adult phantoms with (E) and without (E(0)) subcutaneous adipose tissue added
      to the torso for five fat distributions. Total (anterior plus posterior) fat
      thicknesses ranged from 0 to 38 cm. RESULTS: For 30 cm of additional fat, E/E(0)
      values for 120-kVp chest and 80-kVp abdomen radiographs ranged from approximately
      2 to 31 and 2 to 83 for male patients, respectively, and from 2 to 45 and 2 to 76
      for female patients, respectively, depending on the type of fat distribution and
      patient orientation in the x-ray beam (anteroposterior or posteroanterior).
      Orienting the patient such that the thinnest fat layer was facing away from the x
      ray tube minimized E/E(0), which was well approximated by using the formula
      E/E(0) = [B(t)/B(0)] x exp(kt(DF)), where B(t) and B(0) are the antiscatter grid
      Bucky factors for patient thicknesses of t and t = 20 cm, respectively; k, a
      constant; and t(DF), the distal (beam exit) fat layer thickness. Reductions in
      E/E(0) reached 14% and 20% for the thickest phantoms when x-ray tube voltages
      were increased by 10 and 20 kVp, respectively, for abdominal radiography in the
      male phantom. CONCLUSION: Effective doses from radiographic examinations in the
      extremely obese can exceed 100 mSv from only a small number of abdominal
      examinations and should be minimized to the extent possible and monitored.
      Exponential dose increases for increased subcutaneous fat thicknesses can be
      reduced substantially by positioning the patient so that the thinnest fat layer
      (anterior or posterior) is closest to the image receptor. Increasing the tube
      voltage also reduces the dose-but to a much smaller extent.

PMID- 19403847
TI  - Locally advanced rectal cancer: MR imaging for restaging after neoadjuvant
      radiation therapy with concomitant chemotherapy. Part I. Are we able to predict
      tumor confined to the rectal wall?
AB  - PURPOSE: To retrospectively assess accuracy of magnetic resonance (MR) imaging
      after radiation therapy with concomitant chemotherapy for downsizing of the
      primary lesion to ypT0-2 tumor confined to rectal wall in locally advanced rectal
      cancer, with histopathologic findings as reference standard, and to evaluate
      additional value of volumetric analysis. MATERIALS AND METHODS: The institutional
      review board approved the study and waived informed consent. Sixty-seven patients
      met criteria of the study. T2-weighted MR images obtained before and after
      radiation therapy with concomitant chemotherapy were assessed for tumor stage by
      expert abdominal radiologist, colorectal surgeon, and general radiologist.
      Sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) were calculated; tumor volume was measured (compared with
      Mann-Whitney U test). Findings were correlated with histopathologic findings.
      RESULTS: Sixty-seven patients (38 men, 29 women; mean age, 63 years) who
      underwent radiation therapy with concomitant chemotherapy and surgery (all but
      one) were evaluated. The PPV for prediction of tumor confined to rectal wall
      (ypT0-2) was 91% (10 of 11), 86% (six of seven), and 88% (seven of eight) for
      expert abdominal radiologist, surgeon, and general radiologist, respectively. In
      24 patients, sensitivity was 42% (10), 25% (six), and 29% (seven). ypT0-2 tumors
      had significantly smaller volumes than did ypT3-4 tumors before radiation therapy
      with concomitant chemotherapy (55 vs 92 cm(3), P = .038). Volume reduction rates
      were significantly higher in ypT0-2 than in ypT3-4 tumors (89% vs 61%, P < .001).
      If volume before radiation therapy with concomitant chemotherapy was 50 cm(3) or
      smaller and volume reduction rate was 75% or higher, excised tumor was always
      confined to rectal wall (ypT0-2). By using these criteria, 43% (six of 14) of
      cases with overstaging could have been predicted to be ypT0-2 tumors correctly.
      CONCLUSION: Downsizing to ypT0-2 tumors can be accurately predicted by combining
      morphologic tumor staging predictions with results from volumetric analyses. MR
      images obtained after radiation therapy with concomitant chemotherapy might be
      helpful in more individualized treatment planning.

PMID- 19403848
TI  - Locally advanced rectal cancer: MR imaging for restaging after neoadjuvant
      radiation therapy with concomitant chemotherapy. Part II. What are the criteria
      to predict involved lymph nodes?
AB  - PURPOSE: To prospectively determine diagnostic performance of predictive criteria
      for nodal restaging after radiation therapy with concomitant chemotherapy by
      using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance
      (MR) imaging in patients with rectal cancer. MATERIALS AND METHODS: After
      institutional review board approval and informed consent were obtained, 39
      patients (24 men, 15 women; mean age, 64 years) with rectal cancer underwent
      USPIO-enhanced two-dimensional (2D) T2-weighted fast spin-echo, three-dimensional
      (3D) T1-weighted gradient-echo, and 3D T2*-weighted MR for restaging. Two
      observers evaluated nodes for border irregularity, short- and long-axis
      diameters, and estimated percentage of white region (<30%, 30%-50%, or >50%)
      within the node (3D T2*-weighted images). Ratio of the measured surface area of
      the white region within the black node to the measured surface area of the total
      node (Ratio(A)) was calculated. Signal intensity (SI) in gluteus muscle (SI(GM))
      and in total node (SI(TN)) were used to calculate SI(TN)/SI(GM) ratio.
      Histopathologic findings were reference standard. Receiver operating
      characteristic (ROC) curves were compared and interobserver agreement was
      determined. RESULTS: Lesion-by-lesion analysis was feasible in 201 lymph nodes.
      Area under the ROC curve (AUC) of border and short- and long-axis diameters for
      observer 1 were 0.85, 0.87, and 0.88 and for observer 2 were 0.70, 0.89, and
      0.87, respectively. AUC for estimated percentage of white region within the node,
      Ratio(A), and SI(TN)/SI(GM) ratio for observer 1 were 0.98, 0.99, and 0.62 and
      for observer 2 were 0.97, 0.98, and 0.65, respectively. AUC for USPIO-enhanced MR
      criteria was significantly better than AUC for conventional MR criteria (P <
      .01). All criteria except border irregularity and SI(TN)/SI(GM) ratio showed high
      interobserver agreement (kappa > 0.79). CONCLUSION: The most reliable predictors
      for identifying benign nodes after radiation therapy with concomitant
      chemotherapy by using USPIO-enhanced MR imaging for restaging in patients with
      rectal cancer were estimated percentage of white region within the node and
      Ratio(A). Measurements on standard 2D T2-weighted fast spin-echo images versus
      primary staging results offer reasonably good accuracy to identify benign lymph
      nodes after therapy.

PMID- 19403849
TI  - Fourier X-ray scattering radiography yields bone structural information.
AB  - PURPOSE: To characterize certain aspects of the microscopic structures of
      cortical and trabecular bone by using Fourier x-ray scattering imaging. MATERIALS
      AND METHODS: Protocols approved by the National Institutes of Health Animal Care
      and Use Committee were used to examine ex vivo the hind limb of a rat and the toe
      of a pig. The Fourier x-ray scattering imaging technique involves the use of a
      grid mask to modulate the cone beam and Fourier spectral filters to isolate the
      harmonic images. The technique yields attenuation, scattering, and phase-contrast
      (PC) images from a single exposure. In the rat tibia cortical bone, the
      scattering signals from two orthogonal grid orientations were compared by using
      Wilcoxon signed rank tests. In the pig toe, the heterogeneity of scattering and
      PC signals was compared between trabecular and compact bone regions of uniform
      attenuation by using F tests. RESULTS: In cortical bone, the scattering signal
      was significantly higher (P < 10(-15)) when the grid was parallel to the
      periosteal surface. Trabecular bone, as compared with cortical bone, appeared
      highly heterogeneous on the scattering (P < 10(-34)) and PC (P < 10(-27)) images.
      CONCLUSION: The ordered alignment of the mineralized collagen fibrils in compact
      bone was reflected in the anisotropic scattering signal in this bone. In
      trabecular bone, the porosity of the mineralized matrix accounted for the
      granular pattern seen on the scattering and PC images.

PMID- 19403850
TI  - Low temperature maximizes growth of Crocus vernus (L.) Hill via changes in carbon
      partitioning and corm development.
AB  - In Crocus vernus, a spring bulbous species, prolonged growth at low temperatures
      results in the development of larger perennial organs and delayed foliar
      senescence. Because corm growth is known to stop before the first visual sign of
      leaf senescence, it is clear that factors other than leaf duration alone
      determine final corm size. The aim of this study was to determine whether reduced
      growth at higher temperatures was due to decreased carbon import to the corm or
      to changes in the partitioning of this carbon once it had reached the corm.
      Plants were grown under two temperature regimes and the amount of carbon fixed,
      transported, and converted into a storable form in the corm, as well as the
      partitioning into soluble carbohydrates, starch, and the cell wall, were
      monitored during the growth cycle. The reduced growth at higher temperature could
      not be explained by a restriction in carbon supply or by a reduced ability to
      convert the carbon into starch. However, under the higher temperature regime, the
      plant allocated more carbon to cell wall material, and the amount of glucose
      within the corm declined earlier in the season. Hexose to sucrose ratios might
      control the duration of corm growth in C. vernus by influencing the timing of the
      cell division, elongation, and maturation phases. It is suggested that it is this
      shift in carbon partitioning, not limited carbon supply or leaf duration, which
      is responsible for the smaller final biomass of the corm at higher temperatures.

PMID- 19403851
TI  - The late Na+ current (INa) inhibitor ranolazine attenuates effects of palmitoyl-L
      carnitine to increase late INa and cause ventricular diastolic dysfunction.
AB  - Palmitoyl-L-carnitine (PC), an ischemic metabolite, causes cellular Na(+) and
      Ca(2+) overload and cardiac dysfunction. This study determined whether ranolazine
      [(+/-)-1-piperazineacetamide, N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2
      methoxyphenoxy)propyl]-] attenuates PC-induced Na(+) current and ventricular
      contractile dysfunction of the isolated heart. PC (4 microM, 30 min) increased
      late Na(+) current by 1034 +/- 349% in guinea pig isolated ventricular myocytes;
      ranolazine (10 microM) and tetrodotoxin (TTX, 3 microM) significantly attenuated
      this effect of PC. PC increased left ventricular end-diastolic pressure (LVEDP),
      coronary perfusion pressure (CPP), wall stiffness, and cardiac lactate and
      adenosine release from the isolated heart. Ranolazine (10 microM) significantly
      reduced the PC-induced increase in LVEDP by 72 +/- 6% (n = 6, p < 0.001), reduced
      left ventricular wall stiffness, and attenuated the PC-induced increase of CPP by
      53 +/- 10% (n = 6-7, p < 0.05). Ranolazine (10 microM) reduced the PC-induced
      increases of lactate and adenosine release by 70 +/- 8 and 81 +/- 5%,
      respectively (n = 6, p <or= 0.05 for both). TTX (2 microM) significantly (p <
      0.05) reduced PC-induced increases of CPP and LVEDP. Pretreatment of isolated
      myocytes or hearts with the free radical scavenger tiron (4,5-dihydroxy-1,3
      benzenedisulfonic acid, disodium salt) (1 mM) significantly reduced the effects
      of PC to cause increases of late Na(+) current and LVEDP, respectively, but
      unlike ranolazine or TTX, tiron did not reverse increases of late Na(+) current
      and LVEDP caused by PC. In summary, ranolazine and TTX, inhibitors of the late
      Na(+) current, attenuated the PC-induced ventricular contractile dysfunction and
      increase of coronary resistance in the guinea pig isolated heart.

PMID- 19403852
TI  - The effects of repeated opioid administration on locomotor activity: II.
      Unidirectional cross-sensitization to cocaine.
AB  - Sensitization refers to an increase in sensitivity to the effects of a drug and
      is believed to play a role in the etiology of substance use disorders. Cross
      sensitization has been observed between drugs from different pharmacological
      classes and may play a role in the escalation of drug use in polydrug-abusing
      populations. The purpose of this study was to examine cross-sensitization between
      opioids and cocaine and to determine the extent to which cross-sensitization is
      mediated by an opioid's selectivity for mu, kappa, and delta receptors. Separate
      groups of rats were treated with opioid receptor agonists and antagonists every
      other day for 10 days, and the locomotor effects of cocaine were tested 8 days
      later. The mu agonists, morphine and buprenorphine, and the delta agonist,
      BW373U86 [(+/-)-4-[(R(*))-[(2S(*),5R(*))-2,5-dimethyl-4-(2-propenyl)-1
      piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide hydrochloride],
      produced cross-sensitization to cocaine, such that repeated administration of
      these drugs over a 10-day period significantly enhanced cocaine's locomotor
      effects when tested later. Coadministration of the opioid antagonist naltrexone
      prevented morphine and buprenorphine from producing cross-sensitization.
      Coadministration of naltrexone, but not the delta antagonist naltrindole, also
      prevented BW373U86 from producing cross-sensitization. The kappa agonist
      spiradoline failed to produce cross-sensitization, but coadministration of
      spiradoline prevented morphine and buprenorphine from producing cross
      sensitization. The ability of spiradoline to block cross-sensitization was itself
      blocked by the kappa antagonist nor-binaltorphimine. The mixed mu/kappa opioids
      butorphanol, nalbuphine, and nalorphine did not produce cross-sensitization under
      any condition examined. These data indicate that agonist activity at mu receptors
      positively modulates cross-sensitization between opioids and cocaine, whereas
      agonist activity at kappa receptors negatively modulates this effect.

PMID- 19403853
TI  - The effects of repeated opioid administration on locomotor activity: I. Opposing
      actions of mu and kappa receptors.
AB  - Repeated administration of many addictive drugs leads to a progressive increase
      in their locomotor effects. This increase in locomotor activity often develops
      concomitantly with increases in their positive-reinforcing effects, which are
      believed to contribute to the etiology of substance use disorders. The purpose of
      this study was to examine changes in sensitivity to the locomotor effects of
      opioids after their repeated administration and to determine the role of mu and
      kappa receptors in mediating these effects. Separate groups of rats were treated
      with opioid receptor agonists and antagonists every other day for 10 days, and
      changes in locomotor activity were measured. Repeated administration of the mu
      agonists, morphine and buprenorphine, produced a progressive increase in
      locomotor activity during the treatment period, and this effect was blocked by
      coadministration of the opioid antagonist naltrexone. The kappa agonist
      spiradoline decreased locomotor activity when administered alone and blocked the
      progressive increase in locomotor activity produced by morphine. The ability of
      spiradoline to block morphine-induced increases in locomotor activity was itself
      blocked by pretreatment with the kappa antagonist nor-binaltorphimine. Repeated
      administration of high doses, but not low or moderate doses, of the mixed
      mu/kappa agonists butorphanol, nalbuphine, and nalorphine produced a progressive
      increase in locomotor activity during the treatment period. Doses of butorphanol,
      nalbuphine, and nalorphine that failed to produce a progressive increase in
      locomotor activity when administered alone did so when subjects were pretreated
      with nor-binaltorphimine. These findings suggest that mu and kappa receptors have
      functionally opposing effects on opioid-mediated locomotor activity and
      sensitization-related processes.

PMID- 19403855
TI  - Nervous and vestibular toxicities of acrylonitrile and iminodipropionitrile.

PMID- 19403854
TI  - Signal transducer and activator of transcription 1 (STAT1) is essential for
      chromium silencing of gene induction in human airway epithelial cells.
AB  - Hexavalent chromium (Cr(VI)) promotes lung injury and pulmonary diseases through
      poorly defined mechanisms that may involve the silencing of inducible protective
      genes. The current study investigated the hypothesis that Cr(VI) actively signals
      through a signal transducer and activator of transcription 1 (STAT1)-dependent
      pathway to silence nickel (Ni)-induced expression of vascular endothelial cell
      growth factor A (VEGFA), an important mediator of lung injury and repair. In
      human bronchial airway epithelial (BEAS-2B) cells, Ni-induced VEGFA transcription
      by stimulating an extracellular regulated kinase (ERK) signaling cascade that
      involved Src kinase-activated Sp1 transactivation, as well as increased hypoxia
      inducible factor-1 alpha (HIF-1 alpha) stabilization and DNA binding. Ni
      stimulated ERK, Src, and HIF-1 alpha activities, as well as Ni-induced VEGFA
      transcript levels were inhibited in Cr(VI)-exposed cells. We previously
      demonstrated that Cr(VI) stimulates STAT1 to suppress VEGFA expression. In BEAS
      2B cells stably expressing STAT1 short hairpin RNA, Cr(VI) increased VEGFA
      transcript levels and Sp1 transactivation. Moreover, in the absence of STAT1,
      Cr(VI), and Ni coexposures positively interacted to further increase VEGFA
      transcripts. This study demonstrates that metal-stimulated signaling cascades
      interact to regulate transcription and induction of adaptive or repair responses
      in airway cells. In addition, the data implicate STAT1 as a rate limiting
      mediator of Cr(VI)-stimulated gene regulation and suggest that cells lacking
      STAT1, such as many tumor cell lines, have opposite responses to Cr(VI) relative
      to normal cells.

PMID- 19403856
TI  - Interference of endocrine disrupters with thyroid hormone receptor-dependent
      transactivation.
AB  - Thyroid hormones regulate critical developmental processes and key metabolic
      pathways. A number of natural and synthetic substances have been identified which
      adversely interfere with the endocrine system. These so-called endocrine
      disrupters (ED) have mainly been studied for their impact on the gonadal hormone
      axis. The aim of this work was to develop a novel sensitive and convenient in
      vitro screening assay for the detection and characterization of potential ED of
      thyroid hormone (TH)-dependent transactivation of gene transcription and to apply
      this tool to test relevant environmental and nutritive ED compounds. We
      constructed a TH-responsive luciferase-based reporter plasmid and established a
      reporter gene assay in a 96 well microplate format using the human
      hepatocarcinoma cell line HepG2 as host system. Both the synthetic TH receptor
      (TR) agonist GC-1 and the antagonist NH-3 were used to evaluate the assay.
      Concentration-response data of test compounds (food constituents, isoflavones,
      ultraviolet-absorbers, pesticides, industrial chemicals) were recorded in
      activation assays. In addition, interference with TH-mediated transactivation was
      tested by coincubation of the ED with triiodothyronine (T(3)) in competition
      assays. Most ED tested affected T(3) reporter gene activity at concentrations of
      1 microM or higher and displayed either agonistic or mixed agonistic/antagonistic
      activities. Effects of relevant ED occurred only at relatively high
      concentrations compared with the endogenous TR ligand T(3). However, on basis of
      their high production volumes and potential bioaccumulation of some fat-soluble
      ED our data indicate the need to carefully monitor certain ED for potential
      disruption of the TH system in intact organisms and humans.

PMID- 19403857
TI  - Diet-derived nutrients mediate the inhibition of hypothalamic NPY neurons in the
      arcuate nucleus of mice during refeeding.
AB  - Fasting activates orexigenic neuropeptide Y neurons in the hypothalamic arcuate
      nucleus (ARC) of mice, which is reversed by 2 h refeeding with standard chow.
      Here, we investigated the contribution of diet-derived macronutrients and
      anorectic hormones to the reversal of the fasting-induced ARC activation during 2
      h refeeding. Refeeding of 12-h-fasted mice with a cellulose-based, noncaloric
      mash induced only a small reduction in c-Fos expression. Refeeding with diets,
      containing carbohydrates, protein, or fat alone reversed it similar to chow;
      however, this effect depended on the amount of intake. The fasting-induced ARC
      activation was unchanged by subcutaneously injected amylin, CCK (both 20
      microg/kg), insulin (0.2 U/kg and 0.05 U/kg) or leptin (2.6 mg/kg). Insulin and
      leptin had no effect on c-Fos expression in neuropeptide Y or proopiomelanocortin
      containing ARC neurons. Interestingly, CCK but not amylin reduced the ghrelin
      induced c-Fos expression in the ARC in ad libitum-fed mice, suggesting that CCK
      may inhibit orexigenic ARC neurons when acting together with other feeding
      related signals. We conclude that all three macronutrients and also non
      nutritive, ingestion-dependent signals contribute to an inhibition of orexigenic
      ARC neurons after refeeding. Similar to the previously demonstrated inhibitory in
      vivo action of peptide YY, CCK may be a postprandial mediator of ARC inhibition.

PMID- 19403859
TI  - Short-term blackcurrant extract consumption modulates exercise-induced oxidative
      stress and lipopolysaccharide-stimulated inflammatory responses.
AB  - Exercise-induced oxidative stress is instrumental in achieving the health
      benefits from regular exercise. Therefore, inappropriate use of fruit-derived
      products (commonly applied as prophalytic antioxidants) may counteract the
      positive effects of exercise. Using human exercise and cellular models we found
      that 1) blackcurrant supplementation suppressed exercise-induced oxidative
      stress, e.g., plasma carbonyls (0.9 +/- 0.1 vs. 0.6 +/- 0.1 nmol/mg protein,
      placebo vs. blackcurrant), and 2) preincubation of THP-1 cells with an
      anthocyanin-rich blackcurrant extract inhibited LPS-stimulated cytokine secretion
      [TNF-alpha (16,453 +/- 322 vs. 10,941 +/- 82 pg/ml, control vs. extract, P <
      0.05) and IL-6 (476 +/- 14 vs. 326 +/- 32 pg/ml, control vs. extract, P < 0.05)]
      and NF-kappaB activation. In addition to its antioxidant and anti-inflammatory
      properties, we found that postexercise plasma collected after blackcurrant
      supplementation enhanced the differential temporal LPS-stimulated inflammatory
      response in THP-1 cells, resulting in an early suppression of TNF-alpha (1,741 +/
      32 vs. 1,312 +/- 42 pg/ml, placebo vs. blackcurrant, P < 0.05) and IL-6 (44 +/-
      5 vs. 36 +/- 3 pg/ml, placebo vs. blackcurrant, P < 0.05) secretion after 24 h.
      Furthermore, by using an oxidative stress cell model, we found that preincubation
      of THP-1 cells with hydrogen peroxide (H(2)O(2)) prior to extract exposure caused
      a greater suppression of LPS-stimulated cytokine secretion after 24 h, which was
      not evident when cells were simultaneously incubated with H(2)O(2) and the
      extract. In summary, our findings support the concept that consumption of
      blackcurrant anthocyanins alleviate oxidative stress, and may, if given at the
      appropriate amount and time, complement the ability of exercise to enhance immune
      responsiveness to potential pathogens.

PMID- 19403860
TI  - Microbial experimental evolution.
AB  - Microbes have been widely used in experimental evolutionary studies because they
      possess a variety of valuable traits that facilitate large-scale experimentation.
      Many replicated populations can be cultured in the laboratory simultaneously
      along with appropriate controls. Short generation times and large population
      sizes make microbes ideal experimental subjects, ensuring that many spontaneous
      mutations occur every generation and that adaptive variants can spread rapidly
      through a population. Another highly useful experimental feature is the ability
      to preserve and store ancestral and evolutionarily derived clones. These can be
      revived in parallel to allow the direct measurement of the competitive fitness of
      a descendant compared with its ancestor. The extent of adaptation can thereby be
      measured quantitatively and compared statistically by direct competition among
      derived groups and with the ancestor. Thus, fitness and adaptation need not be
      matters of qualitative speculation, but are quantitatively measurable variables
      in these systems. Replication allows the quantification of heterogeneity in
      responses to imposed selection and thereby statistical distinction between
      changes that are systematic responses to the selective regimen and those that are
      specific to individual populations.

PMID- 19403858
TI  - SOD1 deficiency causes salt sensitivity and aggravates hypertension in
      hydronephrosis.
AB  - Hydronephrosis causes renal dysfunction and salt-sensitive hypertension, which is
      associated with nitric oxide deficiency and abnormal tubuloglomerular feedback
      (TGF) response. We investigated the role of oxidative stress for salt sensitivity
      and for hypertension in hydronephrosis. Hydronephrosis was induced in superoxide
      dismutase 1-transgenic (SOD1-tg), SOD1-deficient (SOD1-ko), and wild-type mice
      and in rats. In mice, telemetric measurements were performed during normal (0.7%
      NaCl) and high-sodium (4% NaCl) diets and with chronic tempol supplementation.
      The 8-iso-prostaglandin-F(2alpha) (F2-IsoPs) and protein excretion profiles and
      renal histology were investigated. The acute effects of tempol on blood pressure
      and TGF were studied in rats. In hydronephrosis, wild-type mice developed salt
      sensitive hypertension (114 +/- 1 to 120 +/- 2 mmHg), which was augmented in SOD1
      ko (125 +/- 3 to 135 +/- 4 mmHg) but abolished in SOD1-tg (109 +/- 3 to 108 +/- 3
      mmHg). SOD1-ko controls displayed salt-sensitive blood pressure (108 +/- 1 to 115
      +/- 2 mmHg), which was not found in wild types or SOD1-tg. Chronic tempol
      treatment reduced blood pressure in SOD1-ko controls (-7 mmHg) and in
      hydronephrotic wild-type (-8 mmHg) and SOD1-ko mice (-16 mmHg), but had no effect
      on blood pressure in wild-type or SOD1-tg controls. SOD1-ko controls and
      hydronephrotic wild-type and SOD1-ko mice exhibited increased fluid excretion
      associated with increased F2-IsoPs and protein excretion. The renal
      histopathological changes found in hydronephrotic wild-type were augmented in
      SOD1-ko and diminished in SOD-tg mice. Tempol attenuated blood pressure and
      normalized TGF response in hydronephrosis [DeltaP(SF): 15.2 +/- 1.2 to 9.1 +/-
      0.6 mmHg, turning point: 14.3 +/- 0.8 to 19.7 +/- 1.4 nl/min]. Oxidative stress
      due to SOD1 deficiency causes salt sensitivity and plays a pivotal role for the
      development of hypertension in hydronephrosis. Increased superoxide formation may
      enhance TGF response and thereby contribute to hypertension.

PMID- 19403861
TI  - Enhancement of Ih, but not inhibition of IM, is a key mechanism underlying the
      PACAP-induced increase in excitability of guinea pig intrinsic cardiac neurons.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) increases excitability
      of guinea pig cardiac neurons, an effect mediated by PACAP-selective PAC(1)
      receptors. In dissociated guinea pig cardiac neurons, PACAP causes a positive
      shift of the voltage dependence of activation of the hyperpolarization-activated
      nonselective cation current (I(h)). This observation suggested that an
      enhancement of I(h) contributed to the increase in excitability in neurons within
      whole-mount cardiac ganglia preparations. To evaluate the role of I(h) in the
      PACAP-induced increase in excitability, we compared the increase in action
      potentials generated by 10 nM PACAP in control neurons and in neurons treated
      with ZD7288 (10 or 100 muM) or CsCl (2 or 2.5 mM), drugs known to inhibit I(h).
      In control cells exposed to PACAP, 1-s depolarizing current pulses elicited
      multiple action potential firing in 79% of the neurons. In ZD7288- or CsCl
      containing solutions, the 10 nM PACAP-induced increase in excitability was
      markedly suppressed, with 7% and 21% of the neurons generating multiple action
      potentials, respectively. Prior results indicated that PACAP initiates
      depolarization by activating an inward current, which is separate from its
      enhancement of I(h). Here, we show that a PACAP-induced depolarization was
      comparable in control neurons and neurons bathed in a CsCl-containing solution,
      an observation indicating that CsCl did not interfere with activation of the
      PAC(1) receptor by PACAP. Additional experiments indicated that pretreatment with
      the putative M current (I(M)) inhibitor 1 mM BaCl(2), but not 10 microM XE991,
      initiated multiple firing in a majority of neurons, with resting potentials
      maintained at approximately -60 mV. Furthermore, in Ba(2+)-treated cells, 10 nM
      PACAP increased the number of action potentials generated. Our results indicate
      that PACAP enhancement of I(h), rather than inhibition of I(M) and other 1 mM
      Ba(2+)-sensitive K(+) currents, is a key ionic mechanism contributing to the
      peptide-induced increase in excitability for neurons within whole-mount cardiac
      ganglia preparations.

PMID- 19403863
TI  - Chronic immunoneutralization of brain angiotensin-(1-12) lowers blood pressure in
      transgenic (mRen2)27 hypertensive rats.
AB  - Angiotensin-(1-12) [ANG-(1-12)] is a newly identified peptide detected in a
      variety of rat tissues, including the brain. To determine whether brain ANG-(1
      12) participates in blood pressure regulation, we treated male adult (mRen2)27
      hypertensive rats (24-28 wk of age) with Anti-ANG-(1-12) IgG or Preimmune IgG via
      an intracerebroventricular cannula for 14 days. Immunoneutralization of brain ANG
      (1-12) lowered systolic blood pressure (-43 +/- 8 mmHg on day 3 and -26 +/- 7
      mmHg on day 10 from baseline, P < 0.05). Water intake was lower on
      intracereroventricular day 6 in the Anti-ANG-(1-12) IgG group, accompanied by
      higher plasma osmolality on day 13, but there were no differences in urine
      volume, food intake, or body weight during the 2-wk treatment. In Preimmune IgG
      treated animals, there were no significant changes in these variables over the 2
      wk period. The antihypertensive effects produced by endogenous neutralization of
      brain ANG-(1-12) suggest that ANG-(1-12) is functionally active in brain pathways
      regulating blood pressure.

PMID- 19403862
TI  - Prenatal programming of rat thick ascending limb chloride transport by low
      protein diet and dexamethasone.
AB  - Prenatal administration of dexamethasone and a low-protein diet has been shown to
      result in hypertension in the offspring when they are adults. The cause for the
      hypertension is unknown. The purpose of this study was to examine whether there
      was prenatal programming of thick ascending limb transport. Rats were
      administered either dexamethasone for 4 days (0.2 mg/kg body wt) by
      intraperitoneal injection daily between the 15th and 18th day of gestation, or
      they were fed a low-protein diet (6% protein) or an isocaloric normal protein
      diet (20% protein) from day 12 gestation until birth. The offspring were studied
      as adults. Prenatal dexamethasone and dietary protein deprivation resulted in an
      increase in blood pressure. Offspring of mothers fed a low-protein diet had an
      increase in medullary but not cortical bumetanide-sensitive Na-K-2Cl
      cotransporter (NKCC2) protein abundance (P < 0.01). There was not a statistically
      significant increase in medullary NKCC2 by prenatal dexamethasone (P = 0.07).
      Both prenatal administration of dexamethasone and a low-protein diet resulted in
      an increase in medullary thick ascending limb chloride transport compared with
      control (298 +/- 33 pmoles x mm(-1) x min(-1), 280 +/- 26 pmoles x mm(-1) x min(
      1), and 191 +/- 21 pmoles x mm(-1) x min(-1), respectively P < 0.05). There was a
      higher lumen-positive transepithelial potential difference in the prenatal
      dexamethasone and low-protein group compared with control as well. Administration
      of furosemide for 24 h resulted in a decrease in blood pressure in the low
      protein group but not the control group. This study demonstrates that insults
      administered to the fetus can program altered sodium transport. Increased tubular
      sodium transport is a likely cause for the hypertension by prenatal programming.

PMID- 19403864
TI  - Changes in cerebral blood flow, cerebral metabolites, and breathing movements in
      the sheep fetus following asphyxia produced by occlusion of the umbilical cord.
AB  - Severe global fetal asphyxia, if caused by a brief occlusion of the umbilical
      cord, results in prolonged cerebral hypoperfusion in fetal sheep. In this study,
      we sought evidence to support the hypothesis that cerebral hypoperfusion is a
      consequence of suppressed cerebral metabolism. In the 24 h following complete
      occlusion of the umbilical cord for 10 min, sagittal sinus blood flow velocity
      was significantly decreased for up to 12 h. Capillary blood flow, measured using
      microspheres, decreased at 1 and 5 h after cord occlusion in many brain regions,
      including cortical gray and white matter. Microdialysis probes implanted in the
      cerebral cortex revealed an increase in extracellular glucose concentrations in
      gray matter for 7-8 h postasphyxia, while lactate increased only briefly,
      suggesting decreased cerebral glucose utilization over this time. Although these
      data, as well as the concurrent suppression of breathing movements and
      electrocortical activity, support the concept of hypometabolic hypoperfusion, the
      significant increase of pyruvate and glycerol concentrations in dialysate fluid
      obtained from the cerebral cortex at 3-8 h after cord occlusion suggests an
      eventual loss of membrane integrity. The prolonged increase of breathing
      movements for many hours suggests loss of the pontine/thalamic control that
      produces the distinct pattern of fetal breathing movements.

PMID- 19403866
TI  - Methods, technology and resources: drivers of discovery.

PMID- 19403867
TI  - The szilard hypothesis on the nature of aging revisited.
AB  - This year marks the 50th anniversary of a nearly forgotten hypothesis on aging by
      Leo Szilard, best known for his pioneering work in nuclear physics, his
      participation in the Manhattan Project during World War II, his opposition to the
      nuclear arms race in the postwar era, and his pioneering ideas in biology. Given
      a specific set of assumptions, Szilard hypothesized that the major reason for the
      phenomenon of aging was aging hits, e.g., by ionizing radiation, to the gene
      bearing chromosomes and presented a mathematical target-hit model enabling the
      calculation of the average and maximum life span of a species, as well as the
      influence of increased exposure to DNA-damaging factors on life expectancy. While
      many new findings have cast doubt on the specific features of the model, this was
      the first serious effort to posit accumulated genetic damage as a cause of
      senescence. Here, we review Szilard's assumptions in the light of current
      knowledge on aging and reassess his mathematical model in an attempt to reach a
      conclusion on the relevance of Szilard's aging hypothesis today.

PMID- 19403871
TI  - IAEA NUMDAB: taking the pulse of nuclear medicine worldwide.

PMID- 19403876
TI  - Quantitative gated SPECT-derived phase analysis on gated myocardial perfusion
      SPECT detects left ventricular dyssynchrony and predicts response to cardiac
      resynchronization therapy.
AB  - The significance of left ventricular (LV) dyssynchrony for the prediction of
      response to cardiac resynchronization therapy (CRT) has been demonstrated.
      Parameters reflecting LV dyssynchrony (phase SD, histogram bandwidth) can be
      derived from gated myocardial perfusion SPECT (GMPS) using phase analysis. The
      feasibility of LV dyssynchrony assessment with phase analysis on GMPS using
      Quantitative Gated SPECT (QGS) software has not been demonstrated in patients
      undergoing CRT. The aim of the present study was to validate the QGS algorithm
      for phase analysis on GMPS in a direct comparison with echocardiography using
      tissue Doppler imaging (TDI) for LV dyssynchrony assessment. Also, prediction of
      response to CRT using GMPS and phase analysis was evaluated. METHODS: Patients (n
      = 40) with severe heart failure (New York Heart Association class III-IV), an LV
      ejection fraction of no more than 35%, and a QRS complex greater than or equal to
      120 ms were evaluated for LV dyssynchrony using GMPS and echocardiography with
      TDI. At baseline and after 6 mo of CRT, clinical status, LV volumes, and LV
      ejection fraction were evaluated. Patients with functional improvement were
      classified as CRT responders. RESULTS: Both histogram bandwidth (r = 0.69, r(2) =
      0.48, SEE = 25.4, P < 0.01) and phase SD (r = 0.65, r(2) = 0.42, SEE = 26.8, P <
      0.01) derived from GMPS correlated significantly with TDI for assessment of LV
      dyssynchrony. At baseline, CRT responders showed a significantly larger histogram
      bandwidth (94 degrees +/- 23 degrees vs. 68 degrees +/- 21 degrees , P < 0.01)
      and a larger phase SD (26 degrees +/- 6 degrees vs. 18 degrees +/- 5 degrees , P
      < 0.01) than did nonresponders. Receiver-operating-characteristic curve analysis
      identified an optimal cutoff value of 72.5 degrees for histogram bandwidth to
      predict CRT response, yielding a sensitivity of 83% and a specificity of 81%. For
      phase SD, sensitivity and specificity similar to those for histogram bandwidth
      were obtained at a cutoff value of 19.6 degrees . CONCLUSION: QGS phase analysis
      on GMPS correlated significantly with TDI for the assessment of LV dyssynchrony.
      Moreover, a high accuracy for prediction of response to CRT was obtained using
      either histogram bandwidth or phase SD.

PMID- 19403868
TI  - Beneficial endocrine but adverse exocrine effects of sitagliptin in the human
      islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions
      with metformin.
AB  - OBJECTIVE: We sought to establish the extent and mechanisms by which sitagliptin
      and metformin singly and in combination modify islet disease progression in human
      islet amyloid polypeptide transgenic (HIP) rats, a model for type 2 diabetes.
      RESEARCH DESIGN AND METHODS: HIP rats were treated with sitagliptin, metformin,
      sitagliptin plus metformin, or no drug as controls for 12 weeks. Fasting blood
      glucose, insulin sensitivity, and beta-cell mass, function, and turnover were
      measured in each group. RESULTS: Sitagliptin plus metformin had synergistic
      effects to preserve beta-cell mass in HIP rats. Metformin more than sitagliptin
      inhibited beta-cell apoptosis. Metformin enhanced hepatic insulin sensitivity;
      sitagliptin enhanced extrahepatic insulin sensitivity with a synergistic effect
      in combination. beta-Cell function was partially preserved by sitagliptin plus
      metformin. However, sitagliptin treatment was associated with increased
      pancreatic ductal turnover, ductal metaplasia, and, in one rat, pancreatitis.
      CONCLUSIONS: The combination of metformin and sitagliptin had synergistic actions
      to preserve beta-cell mass and function and enhance insulin sensitivity in the
      HIP rat model of type 2 diabetes. However, adverse actions of sitagliptin
      treatment on exocrine pancreas raise concerns that require further evaluation.

PMID- 19403877
TI  - Optimizing 131I uptake after rhTSH stimulation in patients with nontoxic
      multinodular goiter: evidence from a prospective, randomized, double-blind study.
AB  - Prestimulation with recombinant human thyroid-stimulating hormone (rhTSH)
      augments radioiodine (131)I therapy for benign nontoxic multinodular goiter. The
      purpose of this study was to determine the optimal time interval between rhTSH
      and (131)I administration to enhance thyroid radioactive iodine uptake (RAIU).
      METHODS: Patients were randomized, in a 2-factorial design, to receive either a
      0.1-mg dose of rhTSH (n = 60) or placebo (n = 30) and to a time interval of 24,
      48, or 72 h before (131)I administration. The rhTSH- or placebo-stimulated RAIU
      study was performed at 4 wk after a baseline RAIU assessment in a tertiary
      referral center at a university hospital. A total of 90 patients (78 women;
      median age, 52 y; range, 22-83 y) referred to (131)I therapy for symptomatic
      nontoxic goiter (median goiter volume, 63 mL; range, 25-464 mL) were included in
      the study. Change in thyroid RAIU was determined at 24 and 96 h after (131)I
      tracer administration. RESULTS: In the placebo subgroups, RAIU did not change
      significantly from baseline. The mean (+/-SE) 24-h RAIU increased from 33.8% +/-
      2.3% to 66.0% +/- 1.8% (111.2% increase) with a 24-h interval, from 36.8% +/-
      2.1% to 64.6% +/- 2.7% (83.3% increase) with a 48-h interval, and from 33.0% +/-
      2.7% to 49.6% +/- 2.5% (62.4% increase) with a 72-h interval. All within-group
      changes were highly significant (P < 0.001). The effect was negatively correlated
      with initial RAIU (r = -0.703, P < 0.001). The increase in 24- and 96-h RAIU was
      significantly higher in the rhTSH/24-h group than it was in the rhTSH/72-h group
      (P = 0.023 and 0.012, respectively) and insignificantly higher than in the
      rhTSH/48-h group (P = 0.37 and 0.26, respectively). CONCLUSION: The effect of
      rhTSH on thyroid RAIU is most pronounced when administered 24 h before (131)I
      administration and declines with longer time intervals. Whether there is a
      similar time dependency for goiter reduction after rhTSH-stimulated (131)I
      therapy remains to be clarified.

PMID- 19403878
TI  - Simultaneous PET imaging of P-glycoprotein inhibition in multiple tissues in the
      pregnant nonhuman primate.
AB  - Studies in rodents indicate that the disruption of P-glycoprotein (P-gp) function
      increases drug distribution into the developing fetus and organs such as the
      brain. To simultaneously and serially evaluate the effect of P-gp activity and
      inhibition on the tissue distribution of drugs in a more representative animal
      model, we tested the feasibility of conducting whole-body PET of the pregnant
      nonhuman primate (Macaca nemestrina). We used (11)C-verapamil as the prototypic P
      gp substrate and cyclosporine A (CsA) as the prototypic inhibitor. METHODS: Four
      pregnant macaques (gestational age, 145-159 d; gestational term, 172 d) were
      imaged after the intravenous administration of (11)C-verapamil (30-72 MBq/kg)
      before and during intravenous infusion of CsA (12 or 24 mg/kg/h, n = 2 each). The
      content of verapamil and its metabolites in plasma samples was determined using a
      rapid solid-phase extraction method. The plasma and tissue time-radioactivity
      concentration curves of (11)C were integrated over 0-9 min after each verapamil
      injection. The tissue or arterial plasma area under the time-concentration curve
      (AUC(tissue)/AUC(plasma)) served as a measure of the tissue distribution of (11)C
      radioactivity. CsA effect on (11)C radioactivity distribution was interpreted as
      P-gp inhibition. The change in the fetal liver AUC ratio served as a reporter of
      placental P-gp inhibition. RESULTS: CsA effect on tissue distribution of (11)C
      radioactivity (AUC ratios) did not increase with the mean blood concentration of
      CsA, indicating a near-maximal P-gp inhibition. CsA increased maternal brain and
      fetal liver distribution of (11)C radioactivity by 276% +/- 88% (P < 0.05) and
      122% +/- 75% (P < 0.05), respectively. Changes in other measured tissues were not
      statistically significant. CONCLUSION: These data demonstrate for the first time,
      to our knowledge, the feasibility of simultaneous, serial, noninvasive imaging of
      P-gp activity and inhibition in multiple maternal organs and the placenta in the
      nonhuman primate. Our findings, consistent with previous data in rodents,
      indicate that the activity of P-gp in the placenta and the blood-brain barrier is
      high and that the inhibition of P-gp facilitates drug distribution across these
      barriers.

PMID- 19403879
TI  - Monitoring and predicting response to therapy with 18F-FDG PET in colorectal
      cancer: a systematic review.
AB  - Molecular imaging with (18)F-FDG PET has been proven useful in the management of
      colorectal cancer. (18)F-FDG PET plays a pivotal role in staging before surgical
      resection of recurrent colorectal cancer and metastases, in the localization of
      recurrence in patients with an unexplained rise in serum carcinoembryonic antigen
      levels, and in the assessment of residual masses after treatment. Currently,
      there is increasing interest in the role of (18)F-FDG PET beyond staging. The
      technique appears to have significant potential for the characterization of
      tumors and for the prediction of prognosis in the context of treatment
      stratification and early assessment of tumor response to therapy. This systematic
      review provides an overview of the literature on the value of (18)F-FDG PET for
      monitoring and predicting the response to therapy in colorectal cancer. The
      review covers chemotherapy response monitoring in advanced colorectal cancer,
      monitoring of the effects of local ablative therapies, and preoperative
      radiotherapy and multimodality treatment response evaluation in primary rectal
      cancer. Given the added value of (18)F-FDG PET for these indications,
      implementation in clinical practice and systematic inclusion in therapeutic
      trials to exploit the potential of (18)F-FDG PET are warranted.

PMID- 19403880
TI  - Monitoring predominantly cytostatic treatment response with 18F-FDG PET.
AB  - (18)F-FDG PET and, more recently, PET/CT have been established as response
      biomarkers for monitoring cytotoxic or cytoreductive cancer therapies. With the
      advent of targeted cancer therapies, which are predominantly cytostatic, (18)F
      FDG PET is increasingly being used to monitor the therapeutic response to these
      agents as well. The impressive outcome of (18)F-FDG PET studies in patients with
      gastrointestinal stromal tumors treated with imatinib mesylate brought to the
      forefront the use of this biomarker for assessing the response to targeted
      therapies. The use of (18)F-FDG PET for this purpose has practical challenges,
      including quantitative analysis and timing of scans. This review provides a
      summary of clinical studies of targeted therapies done to date with (18)F-FDG PET
      and provides guidance on practical issues to ensure the optimal interpretation of
      imaging data in drug development and for patient care.

PMID- 19403882
TI  - Still no time for complacency: Developmental effects of prenatal methamphetamine
      exposure.

PMID- 19403883
TI  - The learning curve for neuroendovascular procedures: how important is it?

PMID- 19403884
TI  - Providing cancer care to a graying and diverse cancer population in the 21st
      century: are we prepared?

PMID- 19403881
TI  - From RECIST to PERCIST: Evolving Considerations for PET response criteria in
      solid tumors.
AB  - The purpose of this article is to review the status and limitations of anatomic
      tumor response metrics including the World Health Organization (WHO) criteria,
      the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This
      article also reviews qualitative and quantitative approaches to metabolic tumor
      response assessment with (18)F-FDG PET and proposes a draft framework for PET
      Response Criteria in Solid Tumors (PERCIST), version 1.0. METHODS: PubMed
      searches, including searches for the terms RECIST, positron, WHO, FDG, cancer
      (including specific types), treatment response, region of interest, and
      derivative references, were performed. Abstracts and articles judged most
      relevant to the goals of this report were reviewed with emphasis on limitations
      and strengths of the anatomic and PET approaches to treatment response
      assessment. On the basis of these data and the authors' experience, draft
      criteria were formulated for PET tumor response to treatment. RESULTS:
      Approximately 3,000 potentially relevant references were screened. Anatomic
      imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely
      applied but still has limitations in response assessments. For example, despite
      effective treatment, changes in tumor size can be minimal in tumors such as
      lymphomas, sarcoma, hepatomas, mesothelioma, and gastrointestinal stromal tumor.
      CT tumor density, contrast enhancement, or MRI characteristics appear more
      informative than size but are not yet routinely applied. RECIST criteria may show
      progression of tumor more slowly than WHO criteria. RECIST 1.1 criteria
      (assessing a maximum of 5 tumor foci, vs. 10 in RECIST) result in a higher
      complete response rate than the original RECIST criteria, at least in lymph
      nodes. Variability appears greater in assessing progression than in assessing
      response. Qualitative and quantitative approaches to (18)F-FDG PET response
      assessment have been applied and require a consistent PET methodology to allow
      quantitative assessments. Statistically significant changes in tumor standardized
      uptake value (SUV) occur in careful test-retest studies of high-SUV tumors, with
      a change of 20% in SUV of a region 1 cm or larger in diameter; however, medically
      relevant beneficial changes are often associated with a 30% or greater decline.
      The more extensive the therapy, the greater the decline in SUV with most
      effective treatments. Important components of the proposed PERCIST criteria
      include assessing normal reference tissue values in a 3-cm-diameter region of
      interest in the liver, using a consistent PET protocol, using a fixed small
      region of interest about 1 cm(3) in volume (1.2-cm diameter) in the most active
      region of metabolically active tumors to minimize statistical variability,
      assessing tumor size, treating SUV lean measurements in the 1 (up to 5 optional)
      most metabolically active tumor focus as a continuous variable, requiring a 30%
      decline in SUV for "response," and deferring to RECIST 1.1 in cases that do not
      have (18)F-FDG avidity or are technically unsuitable. Criteria to define
      progression of tumor-absent new lesions are uncertain but are proposed.
      CONCLUSION: Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1
      criteria have limitations, particularly in assessing the activity of newer cancer
      therapies that stabilize disease, whereas (18)F-FDG PET appears particularly
      valuable in such cases. The proposed PERCIST 1.0 criteria should serve as a
      starting point for use in clinical trials and in structured quantitative clinical
      reporting. Undoubtedly, subsequent revisions and enhancements will be required as
      validation studies are undertaken in varying diseases and treatments.

PMID- 19403885
TI  - American society of clinical oncology policy statement: disparities in cancer
      care.
AB  - The American Society of Clinical Oncology (ASCO) has embarked on an intensive
      campaign to integrate elimination of cancer health disparities into the Society's
      overall mission and activities. Key components of this commitment are enhancing
      awareness of disparities; improving access to care; and supporting research on
      health disparities. Major objectives are to advance the education of the oncology
      community in the care of patients from underserved and minority populations;
      increase the diversity of the clinical oncology workforce as a requisite to
      improving access to cancer care for the underserved; and support research in the
      area of health disparities. Racial and ethnic disparities in cancer care are an
      issue of critical importance to ASCO, the oncology community, and our society at
      large. The health disparities initiative outlined herein enunciates ASCO's
      dedication to eliminating disparities in cancer care and discusses our
      multipronged approach for addressing disparities within the clinical oncology
      community. ASCO is committed to collaborating with the diverse community of
      stakeholders to undertake the following: develop policies to guarantee equal
      access to quality health care, with special emphasis on reducing insurance and
      economic barriers to cancer care; develop a comprehensive plan to increase
      awareness of racial and ethnic disparities in cancer care; execute a strategy to
      enhance the supply of minority physicians and to improve the training of the
      oncology workforce to meet the needs of racially and ethnically diverse cancer
      patients; increase prioritization of public and private research on cancer care
      disparities; develop mechanisms to increase participation of racially and
      ethnically diverse populations in cancer clinical trials; and support initiatives
      to enhance patients' involvement in their cancer care.

PMID- 19403886
TI  - Future of cancer incidence in the United States: burdens upon an aging, changing
      nation.
AB  - PURPOSE: By 2030, the United States' population will increase to approximately
      365 million, including 72 million older adults (age > or = 65 years) and 157
      million minority individuals. Although cancer incidence varies by age and race,
      the impact of demographic changes on cancer incidence has not been fully
      characterized. We sought to estimate the number of cancer patients diagnosed in
      the United States through 2030 by age and race. METHODS: Current demographic
      specific cancer incidence rates were calculated using the Surveillance
      Epidemiology and End Results database. Population projections from the Census
      Bureau were used to project future cancer incidence through 2030. RESULTS: From
      2010 to 2030, the total projected cancer incidence will increase by approximately
      45%, from 1.6 million in 2010 to 2.3 million in 2030. This increase is driven by
      cancer diagnosed in older adults and minorities. A 67% increase in cancer
      incidence is anticipated for older adults, compared with an 11% increase for
      younger adults. A 99% increase is anticipated for minorities, compared with a 31%
      increase for whites. From 2010 to 2030, the percentage of all cancers diagnosed
      in older adults will increase from 61% to 70%, and the percentage of all cancers
      diagnosed in minorities will increase from 21% to 28%. CONCLUSION: Demographic
      changes in the United States will result in a marked increase in the number of
      cancer diagnoses over the next 20 years. Continued efforts are needed to improve
      cancer care for older adults and minorities.

PMID- 19403888
TI  - Hematopoietic stem cell transplantation in Griscelli syndrome type 2: a single
      center report on 10 patients.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative
      treatment for Griscelli syndrome type 2, an inherited immune disorder causing
      fatal hemophagocytic lymphohistiocytosis (HLH). Optimal therapeutic modalities
      are not yet well known. We retrospectively analyzed the outcome for 10 patients
      who underwent HSCT in a single center between 1996 and 2008. Seven patients (70%)
      were cured of the primary immune defect (mean follow-up, 5.2 years; range, 0.8
      12.0 years), 4 of them without neurologic sequelae. In the 3 deceased patients,
      death occurred within 110 days of HSCT and was probably due to adverse reaction
      to HSCT in 2 patients and to HLH relapse in one patient. One patient received 2
      transplants because of graft failure. Clinical events included veno-occlusive
      disease (n = 5), acute (n = 7) or chronic (n = 1) graft-versus-host disease II
      III, and Epstein-Barr virus-induced lymphoproliferative disease (n = 2). Of the 7
      patients with neurologic involvement before HSCT, 4 survived and 2 presented
      sequelae. Furthermore, 1 patient lacking neurologic involvement before HSCT
      developed long-term sequelae. These results demonstrate the efficacy of HSCT in
      curing the immune disorder but also show that neurologic HLH before HSCT is a
      major factor, given the neurologic sequelae after otherwise successful HSCT.
      Additional studies are required to improve treatment.

PMID- 19403889
TI  - Imatinib for refractory chronic graft-versus-host disease with fibrotic features.
AB  - We previously reported that patients with fibrotic, chronic graft-versus-host
      disease (cGVHD) have antibodies activating the platelet-derived growth factor
      receptor pathway. Because this pathway can be inhibited by imatinib, we performed
      a pilot study including 19 patients with refractory cGVHD, given imatinib at a
      starting dose of 100 mg per day. All patients had active cGVHD with measurable
      involvement of skin or other districts and had previously failed at least 2
      treatment lines. Patient median age was 29 years (range, 10-62 years), and median
      duration of cGvHD was 37 months (range, 4-107 months). The organs involved were
      skin (n = 17), lung (n = 11), and bowel (n = 5); 15 patients had sicca syndrome.
      Imatinib-related, grade 3 to 4 toxicity included fluid retention, infections, and
      anemia. Imatinib was discontinued in 8 patients: in 3 because of toxicity and in
      5 because of lack of response (n = 3) or relapse of malignancy (n = 2). Overall
      response rate at 6 months was 79%, with 7 complete remissions (CRs) and 8 partial
      remissions (PRs). With a median follow-up of 17 months, 16 patients are alive, 14
      still in CR or PR. The 18-month probability of overall survival is 84%. This
      study suggests that imatinib is a promising treatment for patients with
      refractory fibrotic cGVHD.

PMID- 19403887
TI  - In search of adrenocortical stem and progenitor cells.
AB  - Scientists have long hypothesized the existence of tissue-specific (somatic) stem
      cells and have searched for their location in different organs. The theory that
      adrenocortical organ homeostasis is maintained by undifferentiated stem or
      progenitor cells can be traced back nearly a century. Similar to other organ
      systems, it is widely believed that these rare cells of the adrenal cortex remain
      relatively undifferentiated and quiescent until needed to replenish the organ, at
      which time they undergo proliferation and terminal differentiation. Historical
      studies examining cell cycle activation by label retention assays and
      regenerative potential by organ transplantation experiments suggested that the
      adrenocortical progenitors reside in the outer periphery of the adrenal gland.
      Over the past decade, the Hammer laboratory, building on this hypothesis and
      these observations, has endeavored to understand the mechanisms of adrenocortical
      development and organ maintenance. In this review, we summarize the current
      knowledge of adrenal organogenesis. We present evidence for the existence and
      location of adrenocortical stem/progenitor cells and their potential contribution
      to adrenocortical carcinomas. Data described herein come primarily from studies
      conducted in the Hammer laboratory with incorporation of important related
      studies from other investigators. Together, the work provides a framework for the
      emerging somatic stem cell field as it relates to the adrenal gland.

PMID- 19403891
TI  - Do tests of executive functioning predict ability to downregulate emotions
      spontaneously and when instructed to suppress?
AB  - Behavioral regulation is a hallmark feature of executive functioning (EF). The
      present study investigated whether commonly used neuropsychological test measures
      of EF (i.e., working memory, Stroop, trail making, and verbal fluency) were
      related to ability to downregulate emotion both spontaneously and when instructed
      to suppress emotional expressions. To ensure a wide range of EF, 24
      frontotemporal lobar degeneration patients, 7 Alzheimer's patients, and 17
      neurologically normal controls participated. Participants were exposed to an
      acoustic startle stimulus (single aversive noise burst) under three conditions:
      (1) unwarned, (2) warned with no instructions (to measure spontaneous emotion
      downregulation), and (3) warned with instructions to suppress (to measure
      instructed emotion downregulation). Results indicated that higher verbal fluency
      scores were related to greater emotion regulation (operationalized as reduction
      in body movement and emotional facial behavior when warned of the impending
      startle) in both regulation conditions. No relationships were found between
      emotion regulation in these conditions and the other EF measures. We conclude
      that, of four commonly used measures of EF, verbal fluency best indexes the
      complex processes of monitoring, evaluation, and control necessary for successful
      emotion regulation, both spontaneously and following instructions to suppress.

PMID- 19403890
TI  - Coarse threat images reveal theta oscillations in the amygdala: a
      magnetoencephalography study.
AB  - Neurocognitive models propose a specialized neural system for processing threat
      related information, in which the amygdala plays a key role in the analysis of
      threat cues. fMRI research indicates that the amygdala is sensitive to coarse
      visual threat relevant information-for example, low spatial frequency (LSF)
      fearful faces. However, fMRI cannot determine the temporal or spectral
      characteristics of neural responses. Consequently, we used magnetoencephalography
      to explore spatiotemporal patterns of activity in the amygdala and cortical
      regions with blurry (LSF) and normal angry, fearful, and neutral faces. Results
      demonstrated differences in amygdala activity between LSF threat-related and LSF
      neutral faces (50-250 msec after face onset). These differences were evident in
      the theta range (4-8 Hz) and were accompanied by power changes within visual and
      frontal regions. Our results support the view that the amygdala is involved in
      the early processing of coarse threat related information and that theta is
      important in integrating activity within emotion-processing networks.

PMID- 19403893
TI  - Catechol-O-methyltransferase Val158Met genotype affects neural correlates of
      aversive stimuli processing.
AB  - It was previously shown that variation of the catechol-O-methyltransferase (COMT)
      gene modulates brain activity during the processing of stimuli with negative
      valence, but not for pleasant stimuli. Here, we tested whether the COMT genotype
      also modulates the electrophysiological correlates of emotional processing and
      explored whether the environmental factor of life stress influences this effect.
      Using the early posterior negativity (EPN) paradigm, event-related brain
      potentials were measured in 81 healthy individuals during the processing of
      pictures that evoked emotions of positive and negative valence. As was
      hypothesized, the COMT genotype affected the EPN amplitudes for unpleasant
      stimuli, but not for pleasant ones. Specifically, Met/Met carriers respond more
      sensitively to unpleasant stimuli, as compared with Val/Val carriers. We did not
      find evidence that life stress moderates the effect of the COMT genotype on
      emotional stimuli processing.

PMID- 19403892
TI  - Recognition of affective prosody in brain-damaged patients and healthy controls:
      a neurophysiological study using EEG and whole-head MEG.
AB  - A passive oddball experiment was used in which stimuli were emotional
      exclamations differing in their affective tone. In both electroencephalography
      (EEG) and magnetoencephalography (MEG), deviants elicited an N300 component,
      sometimes accompanied by a slow wave. Both components had a symmetrical
      distribution, but the former was more posterior than the latter. The same
      responses to prosodic stimuli were significant in 6 of 27 patients with severe
      disorders of consciousness (persistent vegetative state and minimally conscious
      state) and in all 3 of the examined locked-in patients, indicating that the
      procedure can be applied for testing neurological patients. The occurrence of
      significant responses depended on the presence or absence of a lesion to the
      right temporal lobe. Obviously, the N300 depends on the activity of the right
      temporal cortex but does not originate there. We suggest that the component is
      related not to the recognition of affective prosody as such, but to the following
      detection of affective mismatch due to violations of emotional context of
      stimulation.

PMID- 19403894
TI  - Electrophysiological differences in the processing of affective information in
      words and pictures.
AB  - It is generally assumed that affective picture viewing is related to higher
      levels of physiological arousal than is the reading of emotional words. However,
      this assertion is based mainly on studies in which the processing of either words
      or pictures has been investigated under heterogenic conditions. Positive,
      negative, relaxing, neutral, and background (stimulus fragments) words and
      pictures were presented to subjects in two experiments under equivalent
      experimental conditions. In Experiment 1, neutral words elicited an enhanced late
      positive component (LPC) that was associated with an increased difficulty in
      discriminating neutral from background stimuli. In Experiment 2, high-arousing
      pictures elicited an enhanced early negativity and LPC that were related to a
      facilitated processing for these stimuli. Thus, it seems that under some
      circumstances, the processing of affective information captures attention only
      with more biologically relevant stimuli. Also, these data might be better
      interpreted on the basis of those models that postulate a different access to
      affective information for words and pictures.

PMID- 19403895
TI  - An investigation of the neural correlates of attention and effector switching
      using ERPs.
AB  - Event-related brain potentials (ERPs) were used to examine the neural correlates
      of attention and effector switching when one or both types of switches were
      performed on a given trial. The response time data revealed that switch costs
      tended to increase from attention switches to effector switches to
      attention+effector switches. For right-hand responses, attention switching was
      associated with a parietal slow wave and effector switching was associated with a
      central readiness potential. For left-hand responses, attention switching was
      associated with a parietal slow wave, and effector switching was associated with
      a parietal slow wave and a readiness potential. These data suggest that the
      independence of the neural systems supporting attention and effector switching
      may be limited to instances where the dominant hemisphere controls the response.

PMID- 19403896
TI  - Anticipatory reconfiguration elicited by fully and partially informative cues
      that validly predict a switch in task.
AB  - Task-switching studies show no behavioral benefit of partially informative cues.
      However, ERP evidence of an early cue-locked positivity elicited by both fully
      and partially informative cues suggests that both cues trigger an anticipatory
      component of task set reconfiguration (Nicholson, Karayanidis, Davies, & Michie,
      2006). We examined this apparent discrepancy using a cued-trials task-switching
      paradigm with three tasks. The ERP finding of an early cue-locked positivity was
      replicated for both switch-to cues, which validly predicted an upcoming switch
      trial and specified the new task set, and switch-away cues, which validly
      predicted an upcoming switch trial but not the new task set. This component was
      not elicited by a noninformative cue that did not specify whether the task would
      switch or repeat. Switch-away cues resulted in more accurate but not faster
      responding than did noninformative cues. Modeling of decision processes confirmed
      a speed-accuracy trade-off between these conditions and a preparation benefit for
      both switch-to and switch-away cues. These results indicate that both fully and
      partially informative cues elicit an early anticipatory component of task set
      reconfiguration that is reflected in the early cue-locked positivity. We argue
      that the pattern of results is most consistent with a task set inhibition account
      of this early anticipatory component of task set reconfiguration.

PMID- 19403898
TI  - Controlling conflict of interest--proposals from the Institute of Medicine.

PMID- 19403897
TI  - A masked priming ERP study of letter processing using single letters and false
      fonts.
AB  - Previous event-related potential (ERP) research on letter processing has
      suggested that a P150 reflects low-level, featural processing, whereas a P260
      reflects high-level, abstract letter processing. In order to investigate the
      specificity of these effects, ERPs were recorded in a masked priming paradigm
      using matching and nonmatching pairs of letters (e.g., g-g, g-j) and false fonts
      (e.g.,[SYMBOL: SEE TEXT], [SYMBOL: SEE TEXT]). If the P150 priming effect indexes
      featural processing, there should be no effect of condition on the P150, since
      the letters and false fonts shared visual features. If the P260 priming effect
      indexes the processing of abstract letter representations, it should be evident
      only in the letter condition. As was expected, the P150 priming effect was
      similar for letters and false fonts; however, the P260 priming effect was also
      similar between conditions. Thus, the P260 priming effect may not be sensitive to
      abstract letter processing per se, or such processing may be extremely abstract.

PMID- 19403900
TI  - Rationing antiretroviral therapy in Africa--treating too few, too late.

PMID- 19403899
TI  - Images in clinical medicine. Chvostek's sign and carpopedal spasm.

PMID- 19403901
TI  - Dronedarone for atrial fibrillation--an odyssey.

PMID- 19403902
TI  - Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection.
AB  - BACKGROUND: Current therapy for chronic hepatitis C virus (HCV) infection is
      effective in less than 50% of patients infected with HCV genotype 1. Telaprevir,
      a protease inhibitor specific to the HCV nonstructural 3/4A serine protease,
      rapidly reduced HCV RNA levels in early studies. METHODS: We randomly assigned
      patients infected with HCV genotype 1 to one of three telaprevir groups or to the
      control group. The control group (called the PR48 group) received peginterferon
      alfa-2a (180 microg per week) and ribavirin (1000 or 1200 mg per day, according
      to body weight) for 48 weeks, plus telaprevir-matched placebo for the first 12
      weeks (75 patients). The telaprevir groups received telaprevir (1250 mg on day 1
      and 750 mg every 8 hours thereafter) for 12 weeks, as well as peginterferon alfa
      2a and ribavirin (at the same doses as in the PR48 group) for the same 12 weeks
      (the T12PR12 group, 17 patients) or for a total of 24 weeks (the T12PR24 group,
      79 patients) or 48 weeks (the T12PR48 group, 79 patients). The primary outcome
      was a sustained virologic response (an undetectable HCV RNA level 24 weeks after
      the end of therapy). RESULTS: The rate of sustained virologic response was 41%
      (31 of 75 patients) in the PR48 group, as compared with 61% (48 of 79 patients)
      in the T12PR24 group (P=0.02), 67% (53 of 79 patients) in the T12PR48 group
      (P=0.002), and 35% (6 of 17 patients) in the T12PR12 group (this group was
      exploratory and not compared with the control group). Viral breakthrough occurred
      in 7% of patients receiving telaprevir. The rate of discontinuation because of
      adverse events was higher in the three telaprevir-based groups (21%, vs. 11% in
      the PR48 group), with rash the most common reason for discontinuation.
      CONCLUSIONS: Treatment with a telaprevir-based regimen significantly improved
      sustained virologic response rates in patients with genotype 1 HCV, albeit with
      higher rates of discontinuation because of adverse events. (ClinicalTrials.gov
      number, NCT00336479.)

PMID- 19403904
TI  - Clinical practice. Asthma in pregnancy.

PMID- 19403903
TI  - Telaprevir and peginterferon with or without ribavirin for chronic HCV infection.
AB  - BACKGROUND: In patients with chronic infection with hepatitis C virus (HCV)
      genotype 1, treatment with peginterferon alfa and ribavirin for 48 weeks results
      in rates of sustained virologic response of 40 to 50%. Telaprevir is a specific
      inhibitor of the HCV serine protease and could be of value in HCV treatment.
      METHODS: A total of 334 patients who had chronic infection with HCV genotype 1
      and had not been treated previously were randomly assigned to receive one of four
      treatments involving various combinations of telaprevir (1250 mg on day 1, then
      750 mg every 8 hours), peginterferon alfa-2a (180 microg weekly), and ribavirin
      (dose according to body weight). The T12PR24 group (81 patients) received
      telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks, followed by
      peginterferon alfa-2a and ribavirin for 12 more weeks. The T12PR12 group (82
      patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks.
      The T12P12 group (78 patients) received telaprevir and peginterferon alfa-2a
      without ribavirin for 12 weeks. The PR48 (control) group (82 patients) received
      peginterferon alfa-2a and ribavirin for 48 weeks. The primary end point, a
      sustained virologic response (an undetectable HCV RNA level 24 weeks after the
      end of therapy), was compared between the control group and the combined T12P12
      and T12PR12 groups. RESULTS: The rate of sustained virologic response for the
      T12PR12 and T12P12 groups combined was 48% (77 of 160 patients), as compared with
      46% (38 of 82) in the PR48 (control) group (P=0.89). The rate was 60% (49 of 82
      patients) in the T12PR12 group (P=0.12 for the comparison with the PR48 group),
      as compared with 36% (28 of 78 patients) in the T12P12 group (P=0.003; P=0.20 for
      the comparison with the PR48 group). The rate was significantly higher in the
      T12PR24 group (69% [56 of 81 patients]) than in the PR48 group (P=0.004). The
      adverse events with increased frequency in the telaprevir-based groups were
      pruritus, rash, and anemia. CONCLUSIONS: In this phase 2 study of patients
      infected with HCV genotype 1 who had not been treated previously, one of the
      three telaprevir groups had a significantly higher rate of sustained virologic
      response than that with standard therapy. Response rates were lowest with the
      regimen that did not include ribavirin. (ClinicalTrials.gov number, NCT00372385.)

PMID- 19403905
TI  - Aspergillosis.

PMID- 19403906
TI  - Images in clinical medicine. Familial hypercholesterolemia.

PMID- 19403907
TI  - Case records of the Massachusetts General Hospital. Case 14-2009. A 36-year-old
      man with chest pain, dysphagia, and pleural and mediastinal calcifications.

PMID- 19403908
TI  - A step forward in therapy for hepatitis C.

PMID- 19403909
TI  - Clinical decisions. Management of incidental hepatitis C virus infection.

PMID- 19403910
TI  - Peginterferon alfa-2a and ribavirin in Latino and non-Latino whites with
      hepatitis C.

PMID- 19403911
TI  - Blood oxygen on Mount Everest.

PMID- 19403912
TI  - Endometriosis.

PMID- 19403913
TI  - Mortality attributable to smoking in China.

PMID- 19403914
TI  - Vitamin D deficiency in critically ill patients.

PMID- 19403915
TI  - Identification of small-molecule modulators of mouse SVZ progenitor cell
      proliferation and differentiation through high-throughput screening.
AB  - Adult mouse subventricular zone (SVZ) neural stem/progenitor cells are
      multipotent self-renewing cells that retain the capacity to generate the major
      cell types of the central nervous system in vitro and in vivo. The relative ease
      of expanding SVZ cells in culture as neurospheres makes them an ideal model for
      carrying out large-scale screening to identify compounds that regulate neural
      progenitor cell proliferation and differentiation. The authors have developed an
      adenosine triphosphate-based cell proliferation assay using adult SVZ cells to
      identify small molecules that activate or inhibit progenitor cell proliferation.
      This assay was miniaturized to a 1536-well format for high-throughput screening
      (HTS) of >1 million small-molecule compounds, and 325 and 581 compounds were
      confirmed as potential inducers of SVZ cell proliferation and differentiation,
      respectively. A number of these compounds were identified as having a selective
      proliferative and differentiation effect on SVZ cells versus mouse Neuro2a
      neuroblastoma cells. These compounds can potentially be useful pharmacological
      tools to modulate resident stem cells and neurogenesis in the adult brain. This
      study represents a novel application of primary somatic stem cells in the HTS of
      a large-scale compound library.

PMID- 19403917
TI  - Fragment-based screening using surface plasmon resonance technology.
AB  - Surface plasmon resonance (SPR) technology has emerged as a new and powerful
      technique to investigate the interaction between low-molecular-weight molecules
      and target proteins. In the present work, the authors assemble from a large
      compound collection a library of 2226 molecules (fragments having low molecular
      weights between 100 and 300 Da) to screen them for binding to chymase, a serine
      protease. Both the active chymase and a zymogen-like form of the protein were
      used in parallel to distinguish between specific and unspecific binding. The
      relative ligand-binding activity of the immobilized protein was periodically
      measured with a reference compound. The screening experiments were performed at
      25 degrees C at a fragment concentration of 200 microM in the presence of 2%
      DMSO. Applying the filter cascade, affinity-selectivity-competition (competition
      with reference compounds and cross-competition with fragments), 80 compounds show
      up as positive screening hits. Competition experiments between fragments show
      that they bind to different parts of the active site. Of 36 fragments co
      crystallized for X-ray studies, 12 could be located in the active site of the
      protein. These results validate the authors' library and demonstrate that the
      application of SPR technology as a filter in fragment screening can be achieved
      successfully.

PMID- 19403916
TI  - A novel high-throughput screening assay for sickle cell disease drug discovery.
AB  - Although the pathophysiology and molecular basis of sickle cell disease (SCD)
      were described more than half a century ago, an effective and safe therapy is not
      yet available. This may be explained by the lack of a suitable high-throughput
      technique that allows rapid screening of thousands of compounds for their
      antisickling effect. The authors have thus developed a novel high-throughput
      screening (HTS) assay based on detecting the ability of red blood cells (RBC) to
      traverse a column of tightly packed Sephacryl chromatography beads. When
      deoxygenated, sickle RBC are rigid and remain on the top of the column. However,
      when deoxygenated and treated with an effective antisickling agent, erythrocytes
      move through the Sephacryl media and produce a red dot on the bottom of the assay
      tubes. This approach has been adapted to wells in a 384-well microplate. Results
      can be obtained by optical scanning: The size of the red dot is proportional to
      the antisickling effect of the test molecule. The new assay is simple,
      inexpensive, reproducible, requires no special reagents, and should be readily
      adaptable to robotic HTS systems. It has the potential to identify novel drug
      candidates, allowing the development of new therapeutic options for individuals
      affected with SCD.

PMID- 19403918
TI  - The interaction of proline-rich ligands with profilin probed with an enzyme
      linked immunosorbent assay.
AB  - To detect interactions of different proline-rich ligands with profilins, the
      authors developed a simple analytical antibody-based screening method. Profilin I
      or profilin IIa was coated in microplates, and ligand binding was monitored via
      antibody detection. Using purified components, the authors show that the assay is
      very sensitive as nanomolar concentrations of recombinant profilin ligands can be
      used. They further apply this technique to detect interaction of profilin with
      various proline-rich partners, either endogenously present or ectopically
      expressed as tagged fusions, using lysates. With this assay, the authors identify
      Shootin1 as a novel profilin IIa partner. In addition, they demonstrate that this
      assay can be used for studying competition or ternary complex formation. In
      conclusion, they developed a sensitive, easy-to-use, and versatile method for the
      study of the interaction between profilin and different ligands.

PMID- 19403919
TI  - Design, synthesis, and pharmacology of fluorescently labeled analogs of
      serotonin: application to screening of the 5-HT2C receptor.
AB  - Novel fluorescent derivatives of serotonin have been synthesized and used as
      tracers for the development of a 5-HT2C fluorescence polarization assay.
      Serotonin analogs that feature a fluorescent probe attached through an ether
      linkage at the tryptamine 5-position have high affinity for the 5-HT2C receptor,
      and affinity is dependent on both linker length and pendent dye. These variables
      have been optimized to generate Cy3B derivative 5a, which has 10-fold higher 5
      HT2C affinity relative to serotonin (Kd=0.23 nM). In receptor activation
      experiments, 5a acts as a full agonist of 5-HT2C. Upon binding to 5-HT2C cell
      membranes, 5a shows a robust increase in fluorescence polarization (FP) signal.
      In an FP binding assay using 5a as a tracer ligand, Ki values for known 5-HT2C
      agonists and antagonists showed excellent agreement with Ki values from
      radioligand binding (r2=0.93). The FP ligand assay is suitable for high
      throughput drug screening applications with respect to speed of analysis,
      displaceable signal, precision, and sensitivity to various reagents. A 384-well
      based high-throughput assay that is rapid, economical, and predictive of test
      compounds' ability to bind to the 5-HT2C receptor has been compiled and
      validated.

PMID- 19403920
TI  - Beta-arrestin-based Bret2 screening assay for the "non"-beta-arrestin binding CB1
      receptor.
AB  - CB1 receptor (CB1R) antagonists have been demonstrated to be effective in
      treating obesity and related disorders. This study has been focused on
      establishing a beta-arrestin 2-based screening assay for the CB1R using BRET2
      technology. When the existing BRET2 screening platform was applied to the CB1R,
      the authors discovered that the receptor interacted weakly with beta-arrestin 2,
      resulting in unsatisfactory assay performance. To enhance the beta-arrestin
      binding capacity, they replaced the C-terminal tail of the CB1R with tails from
      either the V2 or BRS3 receptors, both of which interact strongly with beta
      arrestin 2. Using this chimeric approach, the authors screened a small compound
      library and identified 21 antagonist and inverse agonist hits with IC50 and EC50
      values ranging from 0.3 nM to 7.5 microM. Both primary and secondary screening
      were performed with Z'>0.5, suggesting that the assay is a robust and cost
      effective alternative to existing cell-based assays.

PMID- 19403921
TI  - Kappa opioid receptor screen with the Tango beta-arrestin recruitment technology
      and characterization of hits with second-messenger assays.
AB  - Assays for high-throughput screening of G-protein-coupled receptors (GPCRs) have
      typically revolved around receptor binding, guanine nucleotide binding, and
      second-messenger assays measuring intracellular cAMP and calcium levels. New
      assay development has been directed toward G-protein-independent signaling
      pathways, including protein redistribution in response to activated receptors.
      beta-arrestin recruitment to agonist-stimulated GPCRs is the basis for the
      Transfluor, PathHunter, and Tango GPCR screening platforms. In the Tango GPCR
      technology, receptor activation results in the recruitment of a TEV protease:beta
      arrestin fusion protein to the activated receptor where the TEV protease releases
      the GAL4-VP16 tethered to the target GPCR by a 7-amino acid TEV protease site.
      The release of the transcription factor results in expression of the beta
      lactamase (bla) reporter gene. The authors performed a small library screen with
      a Tango cell line expressing the kappa opioid receptor and identified a series of
      compounds with a similar core chemical structure that were selective agonists for
      the kappa opioid receptor over the Amicro and delta opioid receptors. These
      compounds were validated in additional second-messenger assays, confirming the
      agonist activity of the identified compounds. These results provide insight into
      the value of screening compounds in multiple assay technologies to better
      characterize the compound's potency and efficacy.

PMID- 19403922
TI  - Screening for NNRTIs with slow dissociation and high affinity for a panel of HIV
      1 RT variants.
AB  - A lead optimization library consisting of 800 HIV-1 nonnucleoside reverse
      transcriptase inhibitors (NNRTIs) was screened in parallel against 4 clinically
      relevant variants of HIV-1 RT (Wt, L100I, Y181C, and K103N) using a surface
      plasmon resonance-based biosensor. The aim was to identify inhibitors suitable in
      specific topical microbicides efficient for preventing the transmission of a
      range of clinically significant strains of HIV-1. The authors hypothesized that
      such compounds should have high affinity and slow dissociation rates for multiple
      variants of the target. To efficiently analyze the large amount of real-time data
      (sensorgrams) that were generated in the screening, they initially used signals
      from 3 selected time points to identify compounds with high affinity and slow
      dissociation for the complete panel of enzyme variants. Hits were confirmed by
      visually inspecting the complete sensorgrams. Two structurally unrelated
      compounds fulfilled the hit criteria, but only 1 compound was found to (a)
      compete with a known NNRTI for binding to the NNRTI site, (b) inhibit HIV-1 RT
      activity, and (c) inhibit HIV-1 replication in cell culture, for all 4 enzyme
      variants. This novel screening methodology offers high-resolution real-time
      kinetic data for multiple targets in parallel. It is expected to have broad
      applicability for the discovery of compounds with defined kinetic profiles,
      crucial for optimal therapeutic effects.

PMID- 19403923
TI  - Development of a cell-based assay for measurement of c-Met phosphorylation using
      AlphaScreen technology and high-content imaging analysis.
AB  - c-Met is a receptor tyrosine kinase (RTK) with a critical role in many
      fundamental cellular processes, including cell proliferation and differentiation.
      Deregulated c-Met signaling has been implicated in both the initiation and
      progression of human cancers and therefore represents an attractive target for
      anticancer therapy. Monitoring the phosphorylation status of relevant tyrosine
      residues provides an important method of assessing c-Met kinase activity. This
      report describes a novel assay to monitor c-Met phosphorylation in cells using
      Amplified Luminescent Proximity Homogeneous Assay (AlphaScreen) technology. Using
      AlphaScreen, the authors were able to detect both global and site-specific
      phosphorylation of c-Met in transformed cell lines. Data obtained from the
      AlphaScreen assay were compared to data obtained from a high-content imaging
      (HCI) method developed in parallel to monitor c-Met phosphorylation at the single
      cell level. The AlphaScreen assay was miniaturized to a 384-well format with
      acceptable signal-to-background ratio (S/B) and Z' statistics and was employed to
      measure c-Met kinase activity in situ after treatment with potent c-Met-specific
      kinase inhibitors. The authors discuss the utility of quantifying endogenous
      cellular c-Met phosphorylation in lead optimization and how the modular design of
      the AlphaScreen assay allows its adaptation to measure cellular activity of other
      kinases.

PMID- 19403925
TI  - Use of a real-time fluorescence monitoring system for high-throughput screening
      for prolyl isomerase inhibitors.
AB  - Cyclophilin is a ubiquitous peptidyl prolyl cis/trans isomerase that plays
      critical roles in many biological processes. A number of cyclophilin inhibitors
      have been designed based on the structure of the immunosuppressant cyclosporin A.
      To discover inhibitors that have other structures, the authors established the
      high-throughput screening (HTS) method using FDSS6000 real-time fluorescence
      detector. The inhibitors identified with this HTS showed significant correlation
      with direct interaction as measured by surface plasmon resonance. This high
      throughput assay system is a powerful tool for the discovery of peptidylprolyl
      isomerase inhibitors.

PMID- 19403924
TI  - New high-throughput fluorimetric assay for discovering inhibitors of UDP-N
      acetylmuramyl-L-alanine: D-glutamate (MurD) ligase.
AB  - A novel assay for monitoring the activity of the bacterial enzyme UDP-N
      acetylmuramyl-L-alanine:D-glutamate ligase (MurD ligase) is presented. MurD,
      which belongs to an enzyme family of Mur ligases, is essential for the synthesis
      of bacterial peptidoglycan and therefore represents an attractive target for the
      discovery of novel antibacterial agents. The inhibition assay described in this
      article is amenable to high-throughput screening. It is based on the detection of
      the accumulation of adenosine 5'-diphosphate (ADP), a product of the reaction
      catalyzed by MurD ligase, by conversion to a fluorescent signal via a coupled
      enzyme system, using the ADP Quest assay kit from DiscoveRx. The novel assay has
      been validated by obtaining KM,app values for substrates D-Glu, UDP- N
      acetylmuramyl-L-alanine (UMA) and ATP that are in agreement with the data
      reported in the literature. A counterscreen assay was introduced to eliminate
      false positives, and some of the known MurD inhibitors have been retested to
      compare the data measured with different methods. Moreover, a focused library of
      around 1000 compounds was screened for the inhibition of MurD to assess the
      performance and robustness of the assay. Finally, a novel MurD inhibitor
      belonging to a new structural class, with an IC50 value of 105 microM, was
      discovered.

PMID- 19403926
TI  - Porcine hypothalamic aromatase cytochrome P450: isoform characterization, sex
      dependent activity, regional expression, and regulation by enzyme inhibition in
      neonatal boars.
AB  - Domestic pigs have three CYP19 genes encoding functional paralogues of the enzyme
      aromatase cytochrome P450 (P450arom) that are expressed in the gonads, placenta,
      and preimplantation blastocyst. All catalyze estrogen synthesis, but the gonadal
      type enzyme is unique in also synthesizing a nonaromatizable biopotent
      testosterone metabolite, 1OH-testosterone (1OH-T). P450arom is expressed in the
      vertebrate brain, is higher in males than females, but has not been investigated
      in pigs, to our knowledge. Therefore, these studies defined which of the porcine
      CYP19 genes was expressed, and at what level, in adult male and female
      hypothalamus. Regional expression was examined in mature boars, and regulation of
      P450arom expression in neonatal boars was investigated by inhibition of P450arom
      with letrozole, which is known to reprogram testicular expression. Pig
      hypothalami expressed the gonadal form of P450arom (redesignated the
      "gonadal/hypothalamic" porcine CYP19 gene and paralogue) based on functional
      analysis confirmed by cloning and sequencing transcripts. Hypothalamic tissue
      synthesized 1OH-T and was sensitive to the selective P450arom inhibitor
      etomidate. Levels were 4-fold higher in male than female hypothalami, with
      expression in the medial preoptic area and lateral borders of the ventromedial
      hypothalamus of boars. In vivo, letrozole-treated neonates had increased
      aromatase activity in hypothalami but decreased activity in testes. Therefore,
      although the same CYP19 gene is expressed in both tissues, expression is
      regulated differently in the hypothalamus than testis. These investigations, the
      first such studies in pig brain to our knowledge, demonstrate unusual aspects of
      P450arom expression and regulation in the hypothalamus, offering promise of
      gaining better insight into roles of P450arom in reproductive function.

PMID- 19403927
TI  - Normalizing gene expression levels in mouse fetal germ cells.
AB  - Real-time PCR has become a popular method to analyze transcription of genes that
      are developmentally regulated during organogenesis of the testes and ovaries.
      However, the heterogenous cell populations and commitment to strikingly different
      developmental pathways of the germ and somatic cells in these organs complicate
      analysis of this process. The selection of suitable reference genes for
      quantifying gene expression in this system is essential, but to date it has not
      been sufficiently addressed. To rectify this problem, we have used fluorescence
      activated cell sorting to purify germ cells from mouse fetal testes and ovaries
      and examined 16 common housekeeping genes for their suitability as reference
      genes. In pure populations of germ cells isolated from Embryonic Day 12.5 (E12.5)
      to E15.5 male and female gonads, Mapk1 and Sdha were identified as the most
      stable reference genes. Analysis of the heterogenous fraction of gonadal somatic
      cells revealed that Canx and Top1 were stable in both sexes, whereas a
      comparative analysis of germ and somatic cell populations identified Canx and
      Mapk1 as suitable reference genes through these developmental stages. Application
      of these reference genes to quantification of gene expression in developing
      gonads revealed that past assays, which employed nonverified reference genes,
      have in some cases provided misleading gene expression profiles. This study has
      identified suitable reference genes to directly compare expression profiles of
      genes expressed in germ and somatic cells of male and female fetal gonads.
      Application of these reference genes to expression analysis in fetal germ and
      somatic cells provides a more accurate system in which to profile gene expression
      in these tissues.

PMID- 19403929
TI  - A botanical extract from channel flow inhibits cell proliferation, induces
      apoptosis, and suppresses CCL5 in human endometriotic stromal cells.
AB  - Growing evidence suggests that medicinal herbs have direct actions on endometrial
      cells. By screening multiple herbs using an in vitro model of endometriosis, we
      found that a commonly used herbal formula exerted considerable antiproliferative
      effects. Our purpose was to investigate the effects of this antiendometriosis
      herbal mixture on cell proliferation, apoptosis, and CCL5 expression and
      secretion in endometriotic stromal cells in vitro. Isolated normal endometrial,
      eutopic, and ectopic endometriotic stromal cells were cultured under established
      conditions. Cell proliferation, apoptosis, and CCL5 gene expression protein
      secretion was evaluated after incubation with different concentrations of an
      antiendometriosis herbal mixture extract. Cell proliferation was assessed by cell
      counting, (3)H-thymidine incorporation, and MTS assays. Apoptosis was determined
      by blotting using anti-cleaved caspase 3 antibodies and by a TUNEL assay. CCL5
      gene expression and protein secretion were determined by transient transfection
      of gene promoter reporters and ELISAs in cell supernatants. Extracts of a
      traditional herbal mixture dose-dependently decreased cell proliferation in
      normal, eutopic, and ectopic endometriotic stromal cells. (3)H-Thymidine uptake
      and MTS confirmed these findings. The herbal extracts induced apoptosis, as
      evidenced by activation of caspase 3 and the presence of TUNEL-positive cells
      after treatment. The herbal extracts also suppressed CCL5 gene transcription and
      protein secretion in endometriotic stromal cells, even when corrected for cell
      number. Extracts from a medicinal herbal mixture have direct effects on cell
      proliferation, apoptosis, and CCL5 production in endometriotic stromal cells. Our
      findings support the further investigation of novel, potentially safe and well
      tolerated botanical products as future endometriosis treatments.

PMID- 19403928
TI  - Constitutive activation of Beta-catenin in uterine stroma and smooth muscle leads
      to the development of mesenchymal tumors in mice.
AB  - Leiomyomas and other mesenchymally derived tumors are the most common neoplasms
      of the female reproductive tract. Presently, very little is known about the
      etiology and progression of these tumors, which are the primary indication for
      hysterectomies. Dysregulated WNT signaling through beta-catenin is a well
      established mechanism for tumorigenesis. We have developed a mouse model that
      expresses constitutively activated beta-catenin in uterine mesenchyme driven by
      the expression of Cre recombinase knocked into the Mullerian-inhibiting substance
      type II receptor promoter locus to investigate its effects on uterine endometrial
      stroma and myometrium. These mice show myometrial hyperplasia and develop
      mesenchymal tumors with 100% penetrance that exhibit histological and molecular
      characteristics of human leiomyomas and endometrial stromal sarcomas. By
      immunohistochemistry, we also show that both transforming growth factor beta and
      the mammalian target of rapamycin are induced by constitutive activation of beta
      catenin. The prevalence of the tumors was greater in multiparous mice, suggesting
      that their development may be a hormonally driven process or that changes in
      uterine morphology during pregnancy and after parturition induce injury and
      repair mechanisms that stimulate tumorigenesis from stem/progenitor cells, which
      normally do not express constitutively activated beta-catenin. Additionally,
      adenomyosis and endometrial gland hyperplasia were occasionally observed in some
      mice. These results show evidence suggesting that dysregulated, stromal, and
      myometrial WNT/beta-catenin signaling has pleiotropic effects on uterine function
      and tumorigenesis.

PMID- 19403931
TI  - Clinical outcome of immunoglobulin light chain amyloidosis affecting the kidney.
AB  - BACKGROUND: The kidney is affected by immunoglobulin light chain amyloidosis (AL)
      in more than 50% of patients who present with the disease, but long-term
      predictors for and outcomes after renal replacement therapy are not well
      described. METHODS: Kaplan-Meier and multivariate analyses were performed in a
      uniformly treated cohort of 145 patients with biopsy-proven AL who were monitored
      for at least 11 years. Outcome measurements were needed for renal replacement
      therapy and survival. RESULTS: Among patients presenting with renal AL, 42%
      ultimately received renal replacement therapy versus 5% of patients who did not
      have this presentation. Patients with renal amyloid who received dialysis support
      had significantly higher serum creatinine and 24-h urine protein levels at
      presentation. Patients with lambda light chain amyloid were significantly more
      likely to have renal involvement and had significantly greater urinary protein
      loss than patients with kappa light chain amyloid. Serum creatinine level was an
      independent predictor of overall survival when corrected for cardiac involvement.
      For 38 patients who received dialysis, median survival from Day 1 of dialysis was
      10.4 months, and 26% of patients with AL ultimately received renal replacement
      therapy versus 42% of patients who presented with renal AL specifically.
      CONCLUSIONS: Presenting 24-h urine protein loss and creatinine values predict
      which patients will require dialysis. Median survival for patients starting
      dialysis is <1 year. The presence of lambda light chain amyloid predicts the
      increased likelihood of renal involvement.

PMID- 19403930
TI  - Estrogen promotes germ cell and seminiferous tubule development in the baboon
      fetal testis.
AB  - The foundation for development of the male reproduction system occurs in utero,
      but relatively little is known about the regulation of primate fetal testis
      maturation. Our laboratories have shown that estrogen regulates key aspects of
      the physiology of pregnancy and fetal development. Therefore, in the present
      study, we characterized and quantified germ cells and Sertoli cells in the fetal
      baboon testis in late normal gestation (i.e., Day 165; term is 184 days) and in
      baboons administered the aromatase inhibitor letrozole throughout the second half
      of gestation to assess the impact of endogenous estrogen on fetal testis
      development. In untreated baboons, the seminiferous cords were comprised of
      undifferentiated (i.e., type A) spermatogonia classified by their morphology as
      dark (Ad) or pale (Ap), gonocytes (precursors of type A spermatogonia),
      unidentified cells (UI), and Sertoli cells. In letrozole-treated baboons, serum
      estradiol levels were decreased by 95%. The number per milligram of fetal testis
      (x10(4)) of Ad spermatogonia (0.42 +/- 0.11) was 45% lower (P = 0.03), and that
      of gonocytes (0.58 +/- 0.06) and UI (0.45 +/- 0.12) was twofold greater (P < 0.01
      and P = 0.06, respectively), than in untreated baboons. Moreover, in the
      seminiferous cords of estrogen-deprived baboons, the basement membrane appeared
      fragmented, the germ cells and Sertoli cells appeared disorganized, and vacuoles
      were present. We conclude that endogenous estrogen promotes fetal testis
      development and that the changes in the germ cell population in the estrogen
      deprived baboon fetus may impair spermatogenesis and fertility in adulthood.

PMID- 19403933
TI  - Extensive-stage small-cell lung cancer--moving beyond response rate?

PMID- 19403932
TI  - Time of onset in haemodialysis access-induced distal ischaemia (HAIDI) is related
      to the access type.
AB  - BACKGROUND: A small portion of haemodialysis patients develop hand ischaemia
      (HAIDI, haemodialysis access-induced distal ischaemia) in the presence of an
      arteriovenous access (AVA). It is unknown if the time of onset of ischaemia is
      related to the type of AVA. This review aims to investigate if a relationship is
      present between the type of AVA and the time of onset and intensity of HAIDI.
      METHODS: Standard databases and reference lists of the pertinent literature were
      systematically searched. HAIDI was classified as 'acute' (<24 h after routine
      access construction), 'subacute' (within 1 month) or 'chronic' (>1 month).
      Location, type and follow-up of AVA were tabulated. RESULTS: Twenty-one studies
      reporting on surgically or percutaneously corrected HAIDI patients (n = 464)
      fulfilled the inclusion criteria. Acute HAIDI strongly (88%) correlated with non
      autogenous AVA. In contrast, chronic HAIDI was predominantly (91%) observed
      following autogenous AVA based on the cubital segment of the brachial artery. A
      simple clinical classification for chronic HAIDI guiding treatment strategies is
      proposed. CONCLUSIONS: Hand ischaemia occurring early after routine access
      surgery is usually related to grafts and not to autogenous access construction.
      If patients have several risk factors for acute hand ischaemia (diabetes),
      nephrologists and vascular surgeons may choose an autogenous AVA. A disadvantage
      of an autogenous access is its association with chronic hand ischaemia,
      particularly if constructed with a brachial artery.

PMID- 19403934
TI  - Brain metastases and subtypes of breast cancer.

PMID- 19403936
TI  - BRCA-deficient animal models and cisplatin resistance.

PMID- 19403935
TI  - Phase II study of sunitinib in men with advanced prostate cancer.
AB  - BACKGROUND: This study explored the efficacy and tolerability of sunitinib, an
      inhibitor of tyrosine kinase receptors, in men with castration-resistant prostate
      cancer (CRPC). METHODS: Men with no prior chemotherapy (group A) and men with
      docetaxel (Taxotere)-resistant prostate cancer (group B) were treated with
      sunitinib. The primary end point was confirmed 50% prostate-specific antigen
      (PSA) decline. Secondary end points included objective response rate and safety.
      Serum-soluble biomarkers were measured. RESULTS: Seventeen men were enrolled in
      each group. One confirmed PSA response was observed in each group, and an
      additional eight men and seven men had stable PSA at week 12 in groups A and B,
      respectively. Improvements in imaging were observed in the absence of post
      treatment PSA declines. Common adverse effects included fatigue, nausea,
      diarrhea, myelosuppression and transaminase elevation. Significant changes
      following sunitinib treatment were observed in serum-soluble biomarkers including
      soluble vascular endothelial growth factor receptor-2, platelet-derived growth
      factor aa, placental growth factor and leptin. CONCLUSIONS: Sunitinib monotherapy
      resulted in few confirmed 50% post-treatment declines in PSA in men with CRPC.
      Serum markers of angiogenesis confirmed on-target effects of sunitinib.
      Assessments of radiographic disease status were often discordant with changes in
      PSA, indicating that alternate end points are important in future trials.

PMID- 19403937
TI  - Ketoconazole retains activity in patients with docetaxel-refractory prostate
      cancer.

PMID- 19403938
TI  - Diethylstilbestrol (DES) retains activity and is a reasonable option in patients
      previously treated with docetaxel for castration-resistant prostate cancer.

PMID- 19403940
TI  - Hypertension as a surrogate marker for the activity of anti-VEGF agents.

PMID- 19403939
TI  - Arterial hypertension and clinical benefit of sunitinib, sorafenib and
      bevacizumab in first and second-line treatment of metastatic renal cell cancer.

PMID- 19403942
TI  - Highly sensitive quantification of serum malonate, a possible marker for de novo
      lipogenesis, by LC-ESI-MS/MS.
AB  - We describe a new sensitive and specific method for the quantification of serum
      malonate (malonic acid, MA), which could be a new biomarker for de novo
      lipogenesis (fatty acid synthesis). This method is based upon a stable isotope
      dilution technique using LC-MS/MS. MA from 50 microl of serum was derivatized
      into di-(1-methyl-3-piperidinyl)malonate (DMP-MA) and quantified by LC-MS/MS
      using the positive electrospray ionization mode. The detection limit of the DMP
      MA was approximately 4.8 fmol (500 fg) (signal-to-noise ratio = 10), which was
      more than 100 times more sensitive compared with that of MA by LC-MS/MS using the
      negative electrospray ionization mode. The relative standard deviations between
      sample preparations and measurements made using the present method were 4.4% and
      3.2%, respectively, by one-way ANOVA. Recovery experiments were performed using
      50 microl aliquots of normal human serum spiked with 9.6 pmol (1 ng) to 28.8 pmol
      (3 ng) of MA and were validated by orthogonal regression analysis. The results
      showed that the estimated amount within a 95% confidence limit was 14.1 +/- 1.1
      pmol, which was in complete agreement with the observed X(0) = 15.0 +/- 0.6 pmol,
      with a mean recovery of 96.0%. This method provides reliable and reproducible
      results for the quantification of MA in human serum.

PMID- 19403944
TI  - School-age children talk about chess: does knowledge drive syntactic complexity?
AB  - PURPOSE: This study examined language productivity and syntactic complexity in
      school-age children in relation to their knowledge of the topic of discussion-the
      game of chess. METHOD: Children (N = 32; mean age = 10;11 [years;months]) who
      played chess volunteered to be interviewed by an adult examiner who had little or
      no experience playing chess. Children's chess knowledge and experience was
      assessed, and each child was classified as a novice or an expert player. Each
      child participated in 3 speaking tasks: General Conversation, Chess Conversation,
      and Chess Explanation. Interviews were audiorecorded, transcribed into Systematic
      Analysis of Language Transcripts (J. F. Miller & R. Chapman, 2003), segmented
      into T-units, and coded for finite clauses. Each speaking task was analyzed for
      total T-units; mean length of T-unit; clausal density; and nominal, relative, and
      adverbial clause use. RESULTS: Total T-units, mean length of T-unit, clausal
      density, and the use of each type of subordinate clause was substantially higher
      in the Chess Explanation task compared with the Chess Conversation task or the
      General Conversation task. Compared with the novices, the experts knew more about
      chess, had played longer, and were stronger players. Nevertheless, the novices
      and experts did not differ on any of the language factors for any of the speaking
      tasks. CONCLUSIONS: Language productivity and syntactic complexity in school-age
      children are strongly influenced by the speaking task. When children are
      presented with a motivating and challenging topic, they rise to the occasion to
      explain the finer details of it to a naive adult.

PMID- 19403943
TI  - Sustained attention in children with specific language impairment (SLI).
AB  - PURPOSE: Information-processing limitations have been associated with language
      problems in children with specific language impairment (SLI). These processing
      limitations may be associated with limitations in attentional capacity, even in
      the absence of clinically significant attention deficits. In this study, the
      authors examined the performance of 4- to 6-year-old children with SLI and their
      typically developing (TD) peers on a visual sustained attention task. It was
      predicted that the children with SLI would demonstrate lower levels of
      performance in the absence of clinically significant attention deficits. METHOD:
      A visual continuous performance task (CPT) was used to assess sustained attention
      in 13 children with SLI (M = 62.07 months) and 13 TD age-matched controls (M =
      62.92 months). All children were screened for normal vision, hearing, and
      attention. Accuracy (d') and response time were analyzed to see if this sustained
      attention task could differentiate between the 2 groups. RESULTS: The children
      with SLI were significantly less accurate but not significantly slower than the
      TD children on this test of visual sustained attention. CONCLUSION: Children with
      SLI may have reduced capacity for sustained attention in the absence of
      clinically significant attention deficits that, over time, could contribute to
      language learning difficulties.

PMID- 19403945
TI  - On the sensitivity and specificity of nonword repetition and sentence recall to
      language and memory impairments in children.
AB  - PURPOSE: The present study examined the utility of 2 measures proposed as markers
      of specific language impairment (SLI) in identifying specific impairments in
      language or working memory in school-age children. METHOD: A group of 400 school
      age children completed a 5-min screening consisting of nonword repetition and
      sentence recall. A subset of low (n = 52) and average (n = 38) scorers completed
      standardized tests of language, short-term and working memory, and nonverbal
      intelligence. RESULTS: Approximately equal numbers of children were identified
      with specific impairments in either language or working memory. A group about
      twice as large had deficits in both language and working memory. Sensitivity of
      the screening measure for both SLI and specific working memory impairments was
      84% or greater, although specificity was closer to 50%. Sentence recall
      performance below the 10th percentile was associated with sensitivity and
      specificity values above 80% for SLI. CONCLUSIONS: Developmental deficits may be
      specific to language or working memory, or include impairments in both areas.
      Sentence recall is a useful clinical marker of SLI and combined language and
      working memory impairments.

PMID- 19403946
TI  - What influences literacy outcome in children with speech sound disorder?
AB  - PURPOSE: In this study, the authors evaluated literacy outcome in children with
      histories of speech sound disorder (SSD) who were characterized along 2
      dimensions: broader language function and persistence of SSD. In previous
      studies, authors have demonstrated that each dimension relates to literacy but
      have not disentangled their effects. Methods Two groups of children (86 SSD and
      37 controls) were recruited at ages 5-6 and were followed longitudinally. The
      authors report the literacy of children with SSD at ages 7-9, compared with
      controls and national norms, and relative to language skill and SSD persistence
      (both measured at age 5-6). RESULTS: The SSD group demonstrated elevated rates of
      reading disability. Language skill but not SSD persistence predicted later
      literacy. However, SSD persistence was associated with phonological awareness
      impairments. Phonological awareness alone predicted literacy outcome less well
      than a model that also included syntax and nonverbal IQ. CONCLUSIONS: Results
      support previous literature findings that SSD history predicts literacy
      difficulties and that the association is strongest for SSD + language impairment
      (LI). Magnitude of phonological impairment alone did not determine literacy
      outcome, as predicted by the core phonological deficit hypothesis. Instead,
      consistent with a multiple deficit approach, phonological deficits appeared to
      interact with other cognitive factors in literacy development.

PMID- 19403947
TI  - Epidemiology of speech and language impairment in a nationally representative
      sample of 4- to 5-year-old children.
AB  - PURPOSE: To draw on multiple sources of information to determine prevalence of
      speech and language impairment in young Australian children. METHOD: Information
      about 4,983 children (ages 4-5 years) from Growing Up in Australia: The
      Longitudinal Study of Australian Children (Australian Institute of Family
      Studies, 2007) was obtained via parent interviews and questionnaires, teacher
      questionnaires, and direct assessment. Data were statistically weighted to the
      Australian population of 253,202 children in the target age group. RESULTS:
      Parent-reported prevalence: 25.2% had concerns about how their child talked and
      made speech sounds (11.8% "concerned"; 13.4% "a little concerned"), and 9.5% had
      concerns about how their child understood language (4.4% "concerned"; 5.1% "a
      little concerned"). Parents who reported concerns identified "speech not clear to
      others" as the most frequent area of difficulty (12.0%). Teacher-reported
      prevalence: 22.3% of children were considered to be less competent than others in
      their expressive language ability (6.7% "much less competent"; 15.6% "less
      competent"); 16.9% were considered to be less competent than others in their
      receptive language ability (4.0% "much less competent"; 12.9% "less competent").
      The match between parent and teacher identification was higher for expressive
      speech and language concern than for receptive language. Direct assessment: 13.0%
      of children were 1-2 SDs below the mean on the Adapted Peabody Picture Vocabulary
      Test-III (S. Rothman, 2003), and a further 1.7% were > 2 SDs below the mean.
      Parent and teacher reports were significantly correlated with scores obtained via
      direct assessment. Period prevalence: Parents and teachers reported that 14.5% of
      children had accessed speech-language pathologist (SLP) services. 2.2% indicated
      that they needed but could not access an SLP. CONCLUSION: Multiple indicators of
      speech and language impairment in diverse contexts confirmed the high prevalence
      of this condition in early childhood and a concomitant need for SLP services.

PMID- 19403948
TI  - Participation of chlorophyll b reductase in the initial step of the degradation
      of light-harvesting chlorophyll a/b-protein complexes in Arabidopsis.
AB  - The light-harvesting chlorophyll a/b-protein complex of photosystem II (LHCII) is
      the most abundant membrane protein in green plants, and its degradation is a
      crucial process for the acclimation to high light conditions and for the recovery
      of nitrogen (N) and carbon (C) during senescence. However, the molecular
      mechanism of LHCII degradation is largely unknown. Here, we report that
      chlorophyll b reductase, which catalyzes the first step of chlorophyll b
      degradation, plays a central role in LHCII degradation. When the genes for
      chlorophyll b reductases NOL and NYC1 were disrupted in Arabidopsis thaliana,
      chlorophyll b and LHCII were not degraded during senescence, whereas other
      pigment complexes completely disappeared. When purified trimeric LHCII was
      incubated with recombinant chlorophyll b reductase (NOL), expressed in
      Escherichia coli, the chlorophyll b in LHCII was converted to 7-hydroxymethyl
      chlorophyll a. Accompanying this conversion, chlorophylls were released from
      LHCII apoproteins until all the chlorophyll molecules in LHCII dissociated from
      the complexes. Chlorophyll-depleted LHCII apoproteins did not dissociate into
      monomeric forms but remained in the trimeric form. Based on these results, we
      propose the novel hypothesis that chlorophyll b reductase catalyzes the initial
      step of LHCII degradation, and that trimeric LHCII is a substrate of LHCII
      degradation.

PMID- 19403950
TI  - Plasma amino acid responses after consumption of beverages with varying protein
      type.
AB  - PURPOSE: To examine how different proteins in a carbohydrate-protein beverage
      affect postprandial amino acid (AA), glucose, and insulin responses. METHODS: Two
      randomized, repeated-measures experiments were performed. In one, 10 volunteers
      drank 3 carbohydrate-protein beverages (380 kcal, 76 g carbohydrate, 19 g
      protein, 2 g fat) in separate (>7 days) trials, each differing in protein type.
      All drinks consisted of cocoa (4 g) and nonfat dry milk (1 g) supplemented with
      casein (CAS), whey (WP), or a casein and whey blend (CAS-WP). Ten additional
      volunteers consumed the same drinks after 60 min of varying-intensity exercise
      (60% and 85% VO2peak). Blood glucose, insulin, glucose-dependent insulinotrophic
      polypeptide (GIP), and AAs were measured every 15-30 min for 4 hr after beverage
      consumption. RESULTS: Branched-chain AA concentrations peaked at 30 min and did
      not differ between beverages at rest (0.69 +/- 0.12 mmol/L) or postexercise (0.70
      +/- 0.07 mmol/L). There were no significant differences between beverages with
      respect to initial (time 0-60) or total area under the curve (time 0-240) for any
      outcome measures at rest or postexercise. CONCLUSION: High-carbohydrate beverages
      containing various proportions of milk proteins procured from a supplier to the
      commercial industry had no impact on AA concentration. Retrospective chemical
      analysis of commercial proteins showed that casein was partially hydrolyzed;
      therefore, consumers should carefully consider the manufacturer (to ensure that
      the product contains intact protein) or other factors (i.e., cost or taste) when
      procuring these beverages for their purported physiological effects.

PMID- 19403949
TI  - Selective survival rescue in 15-lipoxygenase-1-deficient retinal pigment
      epithelial cells by the novel docosahexaenoic acid-derived mediator,
      neuroprotectin D1.
AB  - The integrity of the retinal pigment epithelial (RPE) cell is essential for the
      survival of rod and cone photoreceptor cells. Several stressors, including
      reactive oxygen species, trigger apoptotic damage in RPE cells preceded by an
      anti-inflammatory, pro-survival response, the formation of neuroprotectin D1
      (NPD1), an oxygenation product derived from the essential omega-3 fatty acid
      family member docosahexaenoic acid. To define the ability of NPD1 and other
      endogenous novel lipid mediators in cell survival, we generated a stable
      knockdown human RPE (ARPE-19) cell line using short hairpin RNA to target 15
      lipoxygenase-1. The 15-lipoxygenase-1-deficient cells exhibited 30% of the
      protein expression, and 15-lipoxygenase-2 remained unchanged, as compared with an
      ARPE-19 cell line control established using nonspecific short hairpin RNA
      transfected cells. NPD1 synthesis was stimulated by tumor necrosis factor
      alpha/H2O2-mediated oxidative stress in nonspecific cells (controls), whereas in
      silenced cells, negligible amounts of NPD1, 12(S)- and 15(S)
      hydroxyeicosatetraenoic acid, and lipoxin A4 were found under these conditions.
      Neither control nor the deficient cells showed an increase in 15-lipoxygenase-1
      protein content after 16 h of oxidative stress, suggesting that the increased
      activity of 15-lipoxygenase-1 is due to activation of pre-existing proteins. 15
      Lipoxygenase-silenced cells also displayed an exacerbated sensitivity to
      oxidative stress-induced apoptosis when compared with the control cells. NPD1
      selectively and potently rescued 15-lipoxygenase-silenced cells from oxidative
      stress-induced apoptosis. These results demonstrate that 15-lipoxygenase-1 is
      activated by oxidative stress in ARPE-19 cells and that NPD1 is part of an early
      survival signaling in RPE cells.

PMID- 19403951
TI  - Changes in body composition with yogurt consumption during resistance training in
      women.
AB  - INTRODUCTION: Resistance training is an effective method to decrease body fat
      (BF) and increase fat-free mass (FFM) and fat oxidation (FO). Dairy foods
      containing calcium and vitamin D might enhance these benefits. This study
      investigated the combined effects of habitual yogurt consumption and resistance
      training on body composition and metabolism. METHODS: Untrained women (N = 35)
      participated in an 8-wk resistance-training program. The yogurt group (Y)
      consumed 3 servings of yogurt containing vitamin D per day, and the control
      groups maintained their baseline low-dairy-calcium diet. Postexercise, Y consumed
      1 of the 3 servings/d fat-free yogurt, the protein group consumed an isocaloric
      product without calcium or vitamin D, and the carbohydrate group consumed an
      isocaloric product without protein. Strength, body composition, fasted resting
      metabolic rate (RMR) and FO, and serum 25-hydroxyvitamin D were measured before
      and after training. RESULTS: Calories (kcal x kg-1 x d-1) and protein (g x kg-1 x
      d-1) significantly increased from baseline for Y. FFM increased (main effect p =
      .002) and %BF decreased (main effect .02) for all groups with training, but Group
      x Time interactions were not observed. RMR and FO did not change with training
      for any group. CONCLUSION: Habitual consumption of yogurt during resistance
      training did not augment changes in body composition compared with a low-dairy
      diet. Y decreased %BF as a result of training, however, even with increased
      calorie consumption.

PMID- 19403952
TI  - Carbohydrate ingestion improves performance of a new reliable test of soccer
      performance.
AB  - The aim of the study was to investigate the reliability of a new test of soccer
      performance and evaluate the effect of carbohydrate (CHO) on soccer performance.
      Eleven university footballers were recruited and underwent 3 trials in a
      randomized order. Two of the trials involved ingesting a placebo beverage, and
      the other, a 7.5% maltodextrin solution. The protocol comprised a series of ten 6
      min exercise blocks on an outdoor Astroturf pitch, separated by the performance
      of 2 of the 4 soccer-specific tests, making the protocol 90 min in duration. The
      intensity of the exercise was designed to be similar to the typical activity
      pattern during soccer match play. Participants performed skill tests of
      dribbling, agility, heading, and shooting throughout the protocol. The
      coefficients of variation for dribbling, agility, heading, and shooting were
      2.2%, 1.2%, 7.0%, and 2.8%, respectively. The mean combined placebo scores were
      42.4 +/- 2.7 s, 43.1 +/- 3.7 s, 210 +/- 34 cm, and 212 +/- 17 points for agility,
      dribbling, heading, and kicking, respectively. CHO ingestion led to a combined
      agility time of 41.5 +/- 0.8 s, for dribbling 41.7 +/- 3.5 s, 213 +/- 11 cm for
      heading, and 220 +/- 5 points for kicking accuracy. There was a significant
      improvement in performance for dribbling, agility, and shooting (p < .05) when
      CHO was ingested compared with placebo. In conclusion, the protocol is a reliable
      test of soccer performance, and ingesting CHO leads to an improvement in soccer
      performance.

PMID- 19403953
TI  - Duathlon performance unaltered by short-term changes in dietary fat and
      carbohydrates.
AB  - PURPOSE: This study investigated the effects of short-term dietary changes on
      metabolism and duathlon performance. METHODS: Eleven men underwent a high-fat
      (HF; >65% fat from energy) or a high-carbohydrate (CHO; HC) diet (>60% CHO from
      energy). Energy intake was individualized, and commercially available foods were
      prepared and packaged for each participant 48 hr before they completed a
      laboratory-based duathlon (5-km run, 30 km cycling, and 10-km run). Blood samples
      were obtained before, immediately after, and 1 and 2 hr after the duathlon for
      determination of glucose, insulin, and glucagon. Oxygen consumption, ratings of
      perceived exertion (RPE), and respiratory-exchange ratio were assessed, and fat
      and CHO oxidation were estimated before, during, and after the duathlon. RESULTS:
      Dietary records indicated a significant difference in fat content ingested before
      the duathlons (p < .05). Time to complete the duathlon did not differ between the
      HC- and the HF-diet trials. CHO-oxidation rate was higher during the HC-diet
      trial than during the HF-diet trial (p = .006). Fat-oxidation rates were higher
      in the HF-diet trial than in the HC-diet trial (p = .001). No differences in RPE
      were found between dietary trials. Blood glucose concentration was higher
      immediately after the duathlon in the HC-diet trial than in the HF-diet trial and
      remained higher 1 and 2 hr after the duathlon (p < .05). CONCLUSION: Duathlon
      performance was not altered by short-term changes in dietary fat or CHO
      composition despite higher blood glucose concentrations under the HC condition.

PMID- 19403954
TI  - Improved cycling time-trial performance after ingestion of a caffeine energy
      drink.
AB  - CONTEXT: Not all athletic competitions lend themselves to supplementation during
      the actual event, underscoring the importance of preexercise supplementation to
      extend endurance and improve exercise performance. Energy drinks are composed of
      ingredients that have been found to increase endurance and improve physical
      performance. PURPOSE: The purpose of the study was to investigate the effects of
      a commercially available energy drink, ingested before exercise, on endurance
      performance. METHODS: The study was a double-blind, randomized, crossover design.
      After a 12-hr fast, 6 male and 6 female trained cyclists (mean age 27.3 +/- 1.7
      yr, mass 68.9 +/- 3.2 kg, and VO2 54.9 +/- 2.3 ml x kg-1 x min-1) consumed 500 ml
      of either flavored placebo or Red Bull Energy Drink (ED; 2.0 g taurine, 1.2 g
      glucuronolactone, 160 mg caffeine, 54 g carbohydrate, 40 mg niacin, 10 mg
      pantothenic acid, 10 mg vitamin B6, and 10 microg vitamin B12) 40 min before a
      simulated cycling time trial. Performance was measured as time to complete a
      standardized amount of work equal to 1 hr of cycling at 70% Wmax. RESULTS:
      Performance improved with ED compared with placebo (3,690 +/- 64 s vs. 3,874 +/-
      93 s, p < .01), but there was no difference in rating of perceived exertion
      between treatments. b-Endorphin levels increased during exercise, with the
      increase for ED approaching significance over placebo (p = .10). Substrate
      utilization, as measured by open-circuit spirometry, did not differ between
      treatments. CONCLUSION: These results demonstrate that consuming a commercially
      available ED before exercise can improve endurance performance and that this
      improvement might be in part the result of increased effort without a concomitant
      increase in perceived exertion.

PMID- 19403955
TI  - Conjugated linoleic acid combined with creatine monohydrate and whey protein
      supplementation during strength training.
AB  - PURPOSE: The authors examined the combined effects of conjugated linoleic acid
      (CLA), creatine (C), and whey protein (P) supplementation during strength
      training. METHODS: Sixty-nine participants (52 men, 17 women; M +/- SD age 22.5
      +/-2.5 yr) were randomly assigned (double-blind) to 1 of 3 groups: CCP (6 g/d CLA
      + 9 g/d C + 36 g/d P; n = 22), CP (C + P + placebo oil; n = 25), or P (P +
      placebo oil; n = 22) during 5 wk of strength training (4-5 sets, 6-12
      repetitions, 6 d/wk). Measurements were taken for body composition (air
      displacement plethysmography), muscle thickness (ultrasound) of the flexors and
      extensors of the elbow and knee, 1-repetition-maximum (1-RM) strength (leg press
      and bench press), urinary markers of bone resorption (N-telopeptides, NTx),
      myofibrillar protein catabolism (3-methylhistidine; 3-MH), oxidative stress (8
      isoprostanes), and kidney function (microalbumin) before and after training.
      RESULTS: Contrast analyses indicated that the CCP group had a greater increase in
      bench-press (16.2% +/- 11.3% vs. 9.7% +/- 17.0%; p < .05) and leg-press (13.1% +/
      9.9% vs. 7.7% +/-14.2%; p < .05) strength and lean-tissue mass (2.4% +/- 2.8%
      vs. 1.3% +/-4.1%; p < .05) than the other groups combined. All groups increased
      muscle thickness over time (p < .05). The relative change in 3-MH (CCP -4.7% +/-
      70.2%, CP -0.4% +/- 81.4%, P 20.3% +/- 75.2%) was less in the groups receiving
      creatine (p < .05), with the difference for NTx also close to significance (p =
      .055; CCP -3.4% +/- 66.6%, CP -3.9% +/- 64.9%, P 26.0% +/- 63.8%). There were no
      changes in oxidative stress or kidney function. CONCLUSION: Combining C, CLA, and
      P was beneficial for increasing strength and lean-tissue mass during heavy
      resistance training.

PMID- 19403956
TI  - Dietary supplement use among elite young German athletes.
AB  - Little is known about the prevalence and motives of supplement use among elite
      young athletes who compete on national and international levels. Therefore, the
      current survey was performed to assess information regarding the past and present
      use of dietary supplements among 164 elite young athletes (16.6 +/- 3.0 years of
      age). A 5-page questionnaire was designed to assess their past and present (last
      4 weeks) use of vitamins, minerals, carbohydrate, protein, and fat supplements;
      sport drinks; and other ergogenic aids. Furthermore, information about motives,
      sources of advice, supplement sources, and supplement contamination was assessed.
      Eighty percent of all athletes reported using at least 1 supplement, and the
      prevalence of use was significantly higher in older athletes (p < .05). Among
      supplement users, minerals, vitamins, sport drinks, energy drinks, and
      carbohydrates were most frequently consumed. Only a minority of the athletes
      declared that they used protein/amino acids, creatine, or other ergogenic aids.
      Major motives for supplement use were health related, whereas performance
      enhancement and recommendations by others were less frequently reported.
      Supplements were mainly obtained from parents or by athletes themselves and were
      mostly purchased in pharmacies, supermarkets, and health-food stores. Among all
      athletes, only 36% were aware of the problem of supplement contamination. The
      survey shows that supplement use is common and widespread among German elite
      young athletes. This stands in strong contrast to recommendations by leading
      sport organizations against supplement use by underage athletes.

PMID- 19403957
TI  - Surface characterization of the chitosan membrane after oxygen plasma treatment
      and its aging effect.
AB  - Chitosan has received considerable attention for biomedical applications in
      recent years because of its biocompatibility and biodegradability. In this paper,
      angle-resolved x-ray photoelectron spectroscopy (ARXPS) was carried out to
      investigate the chemical groups' spatial orientation on the chitosan membrane
      surface. Oxygen plasma treatment was also employed to improve the surface
      hydrophilicity of the chitosan membrane. The results of ARXPS revealed the
      distribution of surface polar groups, such as-OH and O=CNH(2) toward the membrane
      bulk, which was the origin of the chitosan membrane surface hydrophobicity. The
      contact angle measurements and XPS results indicated that oxygen plasma treatment
      can markedly improve the surface hydrophilicity and surface energy of the
      chitosan membrane by incorporating oxygen-containing polar groups. With the
      existence of the aging process, the influence of plasma treatment was not
      permanent, it faded with storage time. The ARXPS result discovered that the
      reorientation of polar functional groups generated by plasma treatment toward the
      membrane bulk was primarily responsible for the aging effect.

PMID- 19403958
TI  - Statistical analysis and definition of blockages-prediction formulae for the
      wastewater network of Oslo by evolutionary computing.
AB  - Oslo Vann og Avlopsetaten (Oslo VAV)-the water/wastewater utility in the
      Norwegian capital city of Oslo-is assessing future strategies for selection of
      most reliable materials for wastewater networks, taking into account not only
      material technical performance but also material performance, regarding
      operational condition of the system.The research project undertaken by SINTEF
      Group, the largest research organisation in Scandinavia, NTNU (Norges Teknisk
      Naturvitenskapelige Universitet) and Oslo VAV adopts several approaches to
      understand reasons for failures that may impact flow capacity, by analysing
      historical data for blockages in Oslo.The aim of the study was to understand
      whether there is a relationship between the performance of the pipeline and a
      number of specific attributes such as age, material, diameter, to name a few.
      This paper presents the characteristics of the data set available and discusses
      the results obtained by performing two different approaches: a traditional
      statistical analysis by segregating the pipes into classes, each of which with
      the same explanatory variables, and a Evolutionary Polynomial Regression model
      (EPR), developed by Technical University of Bari and University of Exeter, to
      identify possible influence of pipe's attributes on the total amount of predicted
      blockages in a period of time.Starting from a detailed analysis of the available
      data for the blockage events, the most important variables are identified and a
      classification scheme is adopted.From the statistical analysis, it can be stated
      that age, size and function do seem to have a marked influence on the proneness
      of a pipeline to blockages, but, for the reduced sample available, it is
      difficult to say which variable it is more influencing. If we look at total
      number of blockages the oldest class seems to be the most prone to blockages, but
      looking at blockage rates (number of blockages per km per year), then it is the
      youngest class showing the highest blockage rate. EPR allowed identifying the
      relation between attitude to block and pipe's attributes in order to understand
      what affects the possibility to have a blockage in the pipe. EPR provides
      formulae to compute the accumulated number of blockages for a pipe class at the
      end of a given period of time. Those formulae do not represent simply regression
      models but highlight those variables which affect the physical phenomenon in
      question.

PMID- 19403959
TI  - Potential of turbidity monitoring for real time control of pollutant discharge in
      sewers during rainfall events.
AB  - Turbidity sensors can be used to continuously monitor the evolution of pollutant
      mass discharge. For two sites within the Paris combined sewer system, continuous
      turbidity, conductivity and flow data were recorded at one-minute time intervals
      over a one-year period. This paper is intended to highlight the variability in
      turbidity dynamics during wet weather. For each storm event, turbidity response
      aspects were analysed through different classifications. The correlation between
      classification and common parameters, such as the antecedent dry weather period,
      total event volume per impervious hectare and both the mean and maximum hydraulic
      flow for each event, was also studied. Moreover, the dynamics of flow and
      turbidity signals were compared at the event scale. No simple relation between
      turbidity responses, hydraulic flow dynamics and the chosen parameters was
      derived from this effort. Knowledge of turbidity dynamics could therefore
      potentially improve wet weather management, especially when using pollution-based
      real-time control (P-RTC) since turbidity contains information not included in
      hydraulic flow dynamics and not readily predictable from such dynamics.

PMID- 19403960
TI  - Oxidation of some typical wastewater contaminants (tributyltin, clarithromycin,
      metoprolol and diclofenac) by ozone.
AB  - The rate constants of the reactions of O(3) with some typical wastewater
      pollutants (tributyltin, the macrolide antibiotic clarithromycin, the beta
      blocker metoprolol and the analgesic diclofenac) were determined and some
      mechanistic aspects were elucidated. Except for tributyltin compounds that react
      only slowly with O(3) (k=4-7 M(-1) s(-1)), the compounds react fast (k>10(4) M(
      1) s(-1)) and can be eliminated at low O(3) doses. Clarithromycin reacts at its
      dimethylamino group and yields the corresponding N-oxide that is no longer
      biologically active. The nitrogen is also the major site of O(3) attack in
      diclofenac and in metoprolol. This gives rise to *OH radicals and these are the
      precursors of hydroxylated products and markedly contribute to chloride release
      in diclofenac.

PMID- 19403961
TI  - Effects of exogenous spermidine on subcellular distribution and chemical forms of
      cadmium in Typha latifolia L. under cadmium stress.
AB  - The effects of foliar spraying with spermidine (Spd) on the subcellular
      distribution and chemical speciation of Cd in Typha latifolia L. in hydroponic
      system were investigated. Increased Cd concentration in the medium caused an
      increase of Cd concentration in all tissues and all subcellular fractions, with
      the highest Cd level occurring in roots, followed by rhizomes and leaves and the
      greatest accumulation was in cell walls, soluble fraction and organelle
      containing fractions ranked next, respectively. The greatest amount of Cd was
      found in the extraction of 1 mol.L(-1) NaCl, followed by 2% HAC, deionized water,
      80% ethanol, residues and the least in 0.6 mol.L(-1) HCl. The subcellular
      distribution and different chemical forms of Cd both decreased after Spd
      application and were more inhibited by 0.25 than 0.50 mmol.L(-1) Spd, especially
      in roots at 0.10 mmol.L(-1) Cd treatment. It could be suggested that the
      retention of Cd in roots, cell walls binding with metal, metal ion
      compartmentation in vacuoles and Cd forms existing in undissolved and integrated
      with pectates and protein play an important role in Cd detoxification and Spd
      could enhance the tolerance of cattail to Cd stress.

PMID- 19403962
TI  - Study of an organoclay for the sorption of dissolved organic compounds in the
      wastewaters from offshore platform operation.
AB  - The goal of this research work was to find a sorbent able to selectively retain
      the harmful dissolved compounds in the wastewaters from offshore platform
      operation but not the carboxylic acids and to study the effects of the most
      important parameters on the sorption process. BTX compounds (benzene, toluene and
      p-xylene) and acetic acid were chosen as the representatives of the harmful
      compounds and carboxylic acids groups respectively since they are found in the
      highest concentrations. An organically modified clay was determined to be the
      most suitable sorbent, where performance was evaluated at different values of pH
      (3, 5 and 8), acetic acid concentration (0, 160 and 320 mg/l), salinity (0, 35
      and 70 g/l) and temperature (20, 40 and 60 degrees C). Results show that there is
      a sorption competition between BTX and acetic acid. Sorption of BTX compounds
      decreased with increasing initial acetic acid concentration and temperature, and
      increased proportionally with the salinity. Sorption of acetic acid, however,
      decreased with increasing pH, temperature and salinity.

PMID- 19403963
TI  - Fair and sustainable irrigation water management in the Babai basin, Nepal.
AB  - This paper attempts to find a strategy to provide year-round irrigation for
      cultivating three crops per year in the southern plains of the country taking a
      case study of the Babai basin. Despite having enough flows during the summer for
      growing rice in total 27,000 ha area, the dry season flows of the Babai river can
      irrigate only 6,300 ha in winter and 4,000 ha in spring limiting the cropping
      intensity to 138.50%. It is proposed to irrigate the 7,500 ha southern dry area
      at the right bank bringing water from a large snow-fed river: the Karnali. Water
      balance study of the three irrigation regions to be irrigated from the Babai
      source preserving their existing water rights showed that the year-round
      irrigation at the west with the proposed arrangement will fall short of only 13.9
      million m(3) water volume. At the east side, the head reach area and the tail
      portion will fall short of 19.4 and 66.4 million m(3) of water to insure a
      cropping intensity of 250%. The deficits can be fulfilled by means of capturing
      the excess river water of rainy season in local reservoirs and by making
      conjunctive use of groundwater. The proposed solution is financially,
      environmentally and socially viable being a cost effective, user friendly and
      should be the linchpin towards attaining a sustainable year-round irrigation in
      the region.

PMID- 19403964
TI  - Cost-benefit evaluation of a decentralized water system for wastewater reuse and
      environmental protection.
AB  - This paper proposed a net benefit value (NBV) model for cost-benefit evaluation
      of wastewater treatment and reuse projects, and attention was mainly paid to
      decentralized systems which are drawing wide interests all over the world
      especially in the water-deficient countries and regions. In the NBV model, all
      the factors related to project costs are monetary ones which can be calculated by
      using traditional methods, while many of the factors related to project benefits
      are non-monetary ones which need sophisticated methods for monetization. In this
      regard, the authors elaborated several methods for monetization of the benefits
      from wastewater discharge reduction, local environment improvement, and human
      health protection. The proposed model and methods were applied for the cost
      benefit evaluation of a decentralized water reclamation and reuse project in a
      newly developed residential area in Xi'an, China. The system with dual-pipe
      collection and grey water treatment and reuse was found to be economically
      ineligible (NBV > 0) when all the treated water is reused for artificial pond
      replenishment, gardening and other non-potable purposes by taking into account
      the benefit of water saving. As environmental benefits are further considered,
      the economic advantage of the project is more significant.

PMID- 19403965
TI  - Optimization of measurement campaigns for calibration of a conceptual sewer
      model.
AB  - To simulate hydrological models of combined sewer systems an accurate calibration
      is indispensable. In addition to all sources of uncertainties in data collection
      due to the measurement methods itself, it is a key question which data has to be
      collected to calibrate a hydrological model, how long measurement campaigns
      should last and where that data has to be collected in a spatial distributed
      system as it is neither possible nor sensible to measure the complete system
      characteristics. In this paper we address this question by means of stochastic
      modelling. Using Monte Carlo Simulation different calibration strategies
      (selection of measurement sites, selection of rainfall-events) and different
      calibration parameters (overflow volume, number of overflows) are tested, in
      order to evaluate the influence on predicting the total overflow volume of the
      entire system. This methodology is applied in a case study with the aim to
      calculate the combined sewer overflow (CSO) efficiency. It can be shown that a
      distributed hydrological model can be calibrated sufficiently when calibration is
      done on 30% of all existing CSOs based on long-term observation. Event based
      calibration is limited possible to a limited extend when calibration events are
      selected carefully as wrong selection of calibration events can result in a
      complete failure of the calibration exercise.

PMID- 19403967
TI  - Optimum contracted-for water supply for hotels in arid coastal regions.
AB  - Hotels in arid coastal areas use mainly desalinated water for their domestic
      water demands, and treated wastewater for irrigating green areas. Private water
      companies supply these hotels with their domestic water needs. There is normally
      a contractual agreement stating a minimum requirement that has to be supplied by
      the water company and that the hotel management has to pay for regardless of its
      actual consumption ("contracted-for water supply"). This paper describes a model
      to determine what value a hotel should choose for its contracted-for water supply
      in order to minimize its total annual water costs. An example from an arid
      coastal tourism-dominated city is presented: Sharm El Sheikh, Egypt.The managers
      of hotels with expected high occupancy rates (74% and above) can contract for
      more than 80%. On the other hand, hotels with expected lower occupancy rates (60%
      and less) can contract for less than 70% of the peak daily domestic water demand.
      With a green area ratio of 40 m(2)/room or less, an on-site wastewater treatment
      plant can satisfy the required irrigation demand for an occupancy rate as low as
      42%. Increasing the ratio of green irrigated area to 100 m(2)/room does not
      affect the contracted-for water supply at occupancy rates above 72%; at lower
      occupancy rates, however, on-site treated wastewater is insufficient for
      irrigating the green areas. Increasing the green irrigated area to 120 m(2)/room
      increases the need for additional water, either from externally sourced treated
      wastewater or potable water. The cost of the former is much lower than the latter
      (0.58 versus 1.52 to 2.14 US$/m(3) in the case study area).

PMID- 19403966
TI  - Use of cyanopigment determination as an indicator of cyanotoxins in drinking
      water.
AB  - The indicator function of the fluorescence signals of the cyanopigments
      phycocyanin and phycoerythrin as early warning parameters against the
      microcystins in drinking water was investigated by lab- and pilot-scale studies.
      The early warning function of the fluorescence signals was examined with regard
      to the signals' real-time character, their sensitivity and the behaviour of the
      cyanopigments in different treatment stages in comparison to microcystins.
      Fluorescence measurements confirmed the real-time character, since they can be
      carried out on-site without the pre-concentration of pigments. The limit of
      detection of phycoerythrin is determined at 0.7 microg/L and of phycocyanin at
      5.3 microg/L respectively. If the pigment/microcystin ratio is known and
      calculated to be higher than 1, very low microcystin concentrations can be
      estimated by the fluorescence signals. The compared behaviour of both pigments
      and selected microcystins (MC-LR and MC-RR) during water treatment shows that
      pigments have an early warning function against microcystins in conventional
      treatment stages using pre-oxidation with permanganate, powdered-activated carbon
      and chlorination. In contrast, cyanopigments do not have an early warning
      function if chlorine dioxide is used as a pre-oxidant or final disinfection
      agent. In order to use pigment control measurements in drinking water treatment
      the initial pigment/toxin ratio of the raw water must be known.

PMID- 19403968
TI  - The effect of turbidity levels and Moringa oleifera concentration on the
      effectiveness of coagulation in water treatment.
AB  - Laboratory experiments were carried out to assess the water purification and
      antimicrobial properties of Moringa oleifera (MO). Hence different concentrations
      (25 to 300 mg/L) were prepared from a salt (1 M NaCl) extract of MO fine powder
      and applied to natural surface water whose turbidity levels ranged from 50 to 450
      NTU. The parameters determined before and after coagulation were turbidity, pH,
      colour, hardness, iron, manganese and Escherichia coli. The experiments showed
      that turbidity removal is influenced by the initial turbidity since the lowest
      turbidity removal of 83.2% was observed at 50 NTU, whilst the highest of 99.8%
      was obtained at 450 NTU. Colour removal followed the same trend as the turbidity.
      The pH exhibited slight variations through the coagulation. The hardness removal
      was very low (0 to 15%). However, high removals were achieved for iron (90.4% to
      100%) and manganese (93.1% to 100%). The highest E. coli removal achieved was
      96.0%. Its removal was associated with the turbidity removal. The optimum MO
      dosages were 150 mg/L (50 NTU and 150 NTU) and 125 mg/L for the rest of the
      initial turbidity values. Furthermore all the parameters determined satisfied the
      WHO guidelines for drinking water except for E. coli.

PMID- 19403969
TI  - Hydraulic modelling of sewage exfiltration.
AB  - Exfiltration of waste water in sewer networks represents a potential danger for
      the soil and the aquifer. Various modelling approaches have been proposed to
      quantify sewerage exfiltration and its spatial and temporal variation. Common
      models are based on the law of Darcy, extended by a more or less detailed
      consideration of the expansion of leaks, the characteristics of the soil and the
      colmation layer. In the paper investigations are introduced, which are focused on
      the actual water content of the soil and its influence on exfiltration rates.
      Modelling results with HYDRUS 1D show, that under unsaturated conditions initial
      exfiltration rates are increased compared to saturated conditions. In experiments
      it was found, that the matrix potential increases the tightness of the colmation
      layer. Further a colmation model was deduced, which allows the calculation of the
      thickness and conductivity of the colmation layer.

PMID- 19403970
TI  - Pollutant removal performance of field-scale stormwater biofiltration systems.
AB  - The pollutant removal performance of three separate stormwater biofiltration
      systems in two different climates was assessed. At one of the sites, rain events
      were simulated, while actual runoff events were monitored at the other two sites.
      In all cases, concentrations of total suspended solids (TSS), copper, lead and
      zinc were effectively and reliably reduced, despite variations in inflow
      concentrations. Two biofiltration systems also effectively reduced phosphorus
      concentrations, however the third system discharged elevated phosphorus
      concentrations relative to inflow; this is attributed to poor specification of
      filter media properties. Effluent nitrogen concentrations were more variable at
      all sites and ranged from being substantially lower to considerably higher than
      inflow concentrations. Flow was also measured at two sites, where it was
      determined that volumetric reductions in runoff further improved pollutant
      removal. TSS and heavy metals will be reliably removed by a wide range of soil
      based filter media, as will phopshorus, as long as the phosphorus content of the
      filter media is low. However, nitrogen removal remains a challenge because it is
      easily transformed to soluble forms and is influenced by wetting and drying.
      These results are essentially consistent with related laboratory studies.

PMID- 19403971
TI  - Simulation of ammonium and chromium transport in porous media using coupling
      scheme of a numerical algorithm and a stochastic algorithm.
AB  - The migration of the species of chromium and ammonium in groundwater and their
      effective remediation depend on the various hydro-geological characteristics of
      the system. The computational modeling of the reactive transport problems is one
      of the most preferred tools for field engineers in groundwater studies to make
      decision in pollution abatement. The analytical models are less modular in nature
      with low computational demand where the modification is difficult during the
      formulation of different reactive systems. Numerical models provide more detailed
      information with high computational demand. Coupling of linear partial
      differential Equations (PDE) for the transport step with a non-linear system of
      ordinary differential equations (ODE) for the reactive step is the usual mode of
      solving a kinetically controlled reactive transport equation. This assumption is
      not appropriate for a system with low concentration of species such as chromium.
      Such reaction systems can be simulated using a stochastic algorithm. In this
      paper, a finite difference scheme coupled with a stochastic algorithm for the
      simulation of the transport of ammonium and chromium in subsurface media has been
      detailed.

PMID- 19403972
TI  - Treatment of red wine vinasses with non-conventional substrates for removing
      coloured compounds.
AB  - Vinasses from the wine industry were treated with different materials to remove
      colour as a first step for treatment. Peat, several composts and red mud from
      bauxite refining were evaluated as adsorbents for coloured compounds, and their
      performances compared to that of activated charcoal. Among the materials assayed,
      grape marc vermicompost gave the best results, followed by peat. A sharp decrease
      of absorbance between 400-800 nm took place in vinasses after the treatments with
      these two materials, whereas the other substrates did not reduce the colour of
      the vinasses as did activate charcoal, grape marc vermicompost and peat.
      Moreover, grape marc vermicompost and peat were activated on high temperatures or
      grinding, producing better results in colour removal, although with negative
      effects on the electrical conductivity and nutrient concentration in the
      wastewater. The results of the treatment of vinasses with activated charcoal were
      reproduced and even overcame, in the case of the reduction of the optical density
      of vinasses at 665 nm, using grape marc vermicompost.

PMID- 19403973
TI  - Assessing wastewater dilution in small rivers with high resolution conductivity
      probes.
AB  - Installation and maintenance of flow gauging stations to assess wastewater
      dilution in small creeks is expensive. The method outlined in this paper provides
      a flexible and cheap alternative for situations with dilution factors smaller
      than 10 and unambiguous flow direction. It is shown that conductivity profiles
      from three sampling locations enable accurate identification of the dilution
      factor with an uncertainty of +/-10-30%. Furthermore, much insight can be gained
      on the temporal behavior of both, the receiving water and the wastewater
      treatment system by combined analysis of conductivity and temperature data. In
      this case study the data also enabled identification and tracking down of illegal
      polluters.

PMID- 19403974
TI  - Instrumental characterization of odour: a combination of olfactory and analytical
      methods.
AB  - Odour emissions are a major environmental issue in wastewater treatment plants
      and are considered to be the main cause of disturbance noticed by the exposed
      population. Odour measurement is carried out using analytical or sensorial
      methods. Sensorial analysis, being assigned to the "human sensor", is the cause
      of a considerable uncertainty. In this study a correlation between analytical and
      sensorial methods was investigated. A novel tool was used to both define odour
      indexes and characterise the odour sources and the volatile substances that cause
      annoyance in a wastewater treatment plant, with the aim to remove the subjective
      component in the measure of the odours and define the induced impact. The sources
      and the main chemical substances responsible for the olfactory annoyances were
      identified. Around 36 different substances were detected, with more than half
      being smell relevant components as well as responsible. Dimethyl disulphide was
      identified as key compound. Results highlight the applicability of highly
      correlation between analytical and sensorial methods in odour emission
      monitoring.

PMID- 19403975
TI  - Design and validation of a wind tunnel system for odour sampling on liquid area
      sources.
AB  - The aim of this study is to describe the methods adopted for the design and the
      experimental validation of a wind tunnel, a sampling system suitable for the
      collection of gaseous samples on passive area sources, which allows to simulate
      wind action on the surface to be monitored. The first step of the work was the
      study of the air velocity profiles. The second step of the work consisted in the
      validation of the sampling system. For this purpose, the odour concentration of
      some air samples collected by means of the wind tunnel was measured by dynamic
      olfactometry. The results of the air velocity measurements show that the wind
      tunnel design features enabled the achievement of a uniform and homogeneous air
      flow through the hood. Moreover, the laboratory tests showed a very good
      correspondence between the odour concentration values measured at the wind tunnel
      outlet and the odour concentration values predicted by the application of a
      specific volatilization model, based on the Prandtl boundary layer theory. The
      agreement between experimental and theoretical trends demonstrate that the
      studied wind tunnel represents a suitable sampling system for the simulation of
      specific odour emission rates from liquid area sources without outward flow.

PMID- 19403976
TI  - Fault tree analysis for urban flooding.
AB  - Traditional methods to evaluate flood risk generally focus on heavy storm events
      as the principal cause of flooding. Conversely, fault tree analysis is a
      technique that aims at modelling all potential causes of flooding. It quantifies
      both overall flood probability and relative contributions of individual causes of
      flooding. This paper presents a fault model for urban flooding and an application
      to the case of Haarlem, a city of 147,000 inhabitants. Data from a complaint
      register, rainfall gauges and hydrodynamic model calculations are used to
      quantify probabilities of basic events in the fault tree. This results in a flood
      probability of 0.78/week for Haarlem. It is shown that gully pot blockages
      contribute to 79% of flood incidents, whereas storm events contribute only 5%.
      This implies that for this case more efficient gully pot cleaning is a more
      effective strategy to reduce flood probability than enlarging drainage system
      capacity. Whether this is also the most cost-effective strategy can only be
      decided after risk assessment has been complemented with a quantification of
      consequences of both types of events. To do this will be the next step in this
      study.

PMID- 19403977
TI  - Application of Eriobotrya japonica (Thunb.) Lindley (Loquat) seed biomass as a
      new biosorbent for the removal of malachite green from aqueous solution.
AB  - A new biosorbent, Eriobotrya japonica (loquat) seed biomass, has been
      investigated in order to remove malachite green (MG) from aqueous solutions. The
      factors affecting the biosorption process such as adsorbent dosage, pH of the
      solution and contact time were studied. The results showed that as the dose of
      loquat seed increased, the percentage of MG biosorption decreased accordingly.
      The experimental data suggested that the maximum pH for efficient biosorption of
      MG was 5.0. The biosorption process was relatively fast and equilibrium was
      achieved after about 60 min. Freundlich and Langmuir adsorption isotherm models
      were used for adsorption equilibrium data and based on the Langmuir isotherm
      plots the maximum bisorption capacity (Q(max)) value was calculated to be 57.47
      mg/g at 20 degrees C. The biosorption kinetics was determined by fitting pseudo
      first-order and pseudo-second-order kinetic models to the experimental data, with
      the second-order model providing the best description of MG biosorption onto
      loquat seed. Various thermodynamic parameters such as free energy change
      DeltaG(0), enthalpy of sorption DeltaH(0) and entropy DeltaS(0) were estimated.
      The positive value of DeltaH(0) and negative values of DeltaG(0) show the
      sorption process is endothermic and spontaneous. The positive value of DeltaS(0)
      shows the increased randomness at the solid-liquid interface during the
      biosorption of dyes onto loquat seed.

PMID- 19403978
TI  - Removal of guar and humus from water by layered double hydroxides.
AB  - Natural organic matter such as guar and humus are recalcitrant to conventional
      pretreatment technologies and can potentially foul processes such as membranes
      during water treatment. An innovative method of using synthetic layered double
      hydroxides (LDH) was investigated for removing common natural organic matter in
      the form of guar gum (GG) and humic acid (HA) from water. Adsorption isotherms
      were evaluated with Langmuir and Freundlich models. Results show the affinity of
      GG and HA to LDH to be 11.31 and 9.33 mg g(-1) LDH, respectively. Kinetic
      isotherms indicate that the sorbing rates of LDH to GG and HA increase with
      initial GG and HA concentrations, fitting a pseudo-second order model. This study
      demonstrate that LDH may be an effective material in removing GG and HA from
      waters and offer an alternative to conventional pretreatment technologies for the
      mitigation fouling of membrane and other systems in water treatment.

PMID- 19403979
TI  - Proficiency testing as the key element in implementing EN13275 olfactometry.
AB  - The technical standard for dynamic olfactometry EN13725:2003 is now widely
      applied in testing of odours for environmental management purposes. Many
      laboratories working in this field apply QA/QC systems according to ISO17025 and
      are accredited under international accreditation, e.g. European Accreditation and
      NATA (Australia). One of the key elements of the EN13725 standard is the
      requirement to attain defined levels of statistical performance parameters, in
      particular Precision under repeatability conditions r and Accuracy A. For the
      reference odour n-butanol laboratories can establish these performance
      characteristics in-house, through internal QA/QC measurements. However, the real
      proof of the pudding is to demonstrate compliance with the requirements in
      externally organised blind proficiency testing. Proficiency testing for
      olfactometry has been used since the mid 1980s in the Netherlands and Germany.
      Currently international proficiency tests are organised by private firm Olfatec,
      under EN ISO/IEC 17020:2004 accreditation. In 2007 the most recent test was held,
      with 29 laboratories participating in the extended proficiency test using n
      butanol. Of the participating laboratories 12 fully complied with the statistical
      performance criteria of EN13725. This result confirms that the EN13725
      performance criteria are attainable in practice. It also shows that the majority
      of laboratories claiming to work according to EN13725 actually fail to do so on
      the key issue of the performance characteristics, a key element of the EN13725
      standard. Even more worrying is that among the laboratories that fail to attain
      the required performance, many are accredited under ISO17025. Of 36 accredited
      laboratories for olfactometry in Europe only 12 have demonstrated compliance in
      2007. This situation may create a false sense of security among users of the data
      produced, trusting that they can apply uncertainties according to EN13725 while
      in fact the uncertainty can be larger. It is therefore very important that
      corrective actions are implemented, and that the accreditation organisations
      monitor the implementation and also ensure that all laboratories claiming to work
      according to EN13725 under ISO17025 accreditation actually are able to attain the
      minimum criteria for precision and accuracy in successive proficiency tests. For
      users of olfactometry results it must be absolutely clear that a laboratory
      working according to EN13725 under ISO17025 accreditation will deliver results
      with a defined and satisfactory uncertainty. Such laboratories must be able to
      consistently pass proficiency tests for olfactometry. Accreditation bodies are
      the key guardians of this reasonable expectation..

PMID- 19403980
TI  - Ferric ion adsorption and electrodesorption by carbon nanotubes and nanofibres
      films.
AB  - Carbon nanotubes and nanofibres (CNTs-CNFs) films have been grown on Ni sheets by
      low pressure chemical vapor deposition system and show good physical adsorption
      capability for ferric (Fe(3 + )) ions. The studies of adsorption kinetics and
      isotherms indicate that Fe(3 + ) adsorption process was regarded as first-order
      model and followed a Langmuir isotherm indicating monolayer adsorption. The
      saturated CNTs-CNFs film is easy to be regenerated by electrodesorption with
      direct voltage applied. The result shows that the combination of adsorption and
      electrodesorption by CNTs-CNFs is a promising technology to remove the Fe(3 + )
      contamination in solution, which can be further extended to the process of other
      heavy metal ions.

PMID- 19403981
TI  - An investigation into advanced oxidation of three chlorophenoxy pesticides in
      surface water.
AB  - The performance of Fenton's reagent in removing 2,4-D, MCPA and mecoprop from
      surface water has been evaluated here. Initial trials were undertaken at a
      pesticide concentration of 4.5 x 10(-5) mol l(-1) in deionised water at pH 3 and
      two different stoichiometric ratios of pesticide: Fe(II): H(2)O(2) (1:1:10,
      1:10:10) were evaluated. At the 1:1:10 ratio, approximately 10 minutes were
      required to achieve a 50% removal of the pesticide. At the higher ratio the
      removal achieved after 1 minute, was >90%. Subsequent experiments studied the
      performance of Fenton (4.5 x 10(-4) mol l(-1) Fe(II): 4.5 x 10(-4) mol l(-1)
      H(2)O(2)) in surface water spiked with pesticides and the impact of pH on the
      rate and degree of pesticide degradation was investigated. The removal was
      significantly improved at pH 3 in comparison to pH 6.5. The effect of Fenton on
      DOC removal from surface water was followed. Experiments investigated the
      performance of Fenton at pesticide concentrations of 7.5 x 10(-9) mol l(-1) in
      surface water. Fenton was shown to be an effective treatment for removing low
      levels of pesticides from surface waters at pH 3 & 4.

PMID- 19403982
TI  - Suitability of adsorption isotherms for predicting the retention capacity of
      active slag filters removing phosphorus from wastewater.
AB  - Active slag filters are an emerging technology for removing phosphorus (P) from
      wastewater. A number of researchers have suggested that adsorption isotherms are
      a useful tool for predicting P retention capacity. However, to date the
      appropriateness of using isotherms for slag filter design remains unverified due
      to the absence of benchmark data from a full-scale, field filter operated to
      exhaustion. This investigation compared the isotherm-predicted P retention
      capacity of a melter slag with the P adsorption capacity determined from a full
      scale, melter slag filter which had reached exhaustion after five years of
      successfully removing P from waste stabilization pond effluent. Results from the
      standard laboratory batch test showed that P adsorption correlated more strongly
      with the Freundlich Isotherm (R(2)=0.97, P<0.01) than the Langmuir Isotherm, a
      similar finding to previous studies. However, at a P concentration of 10 mg/L,
      typical of domestic effluent, the Freundlich equation predicted a retention
      capacity of 0.014 gP/kg slag; markedly lower than the 1.23 gP/kg slag adsorbed by
      the field filter. Clearly, the result generated by the isotherm bears no
      resemblance to actual field capacity. Scanning electron microscopy analysis
      revealed porous, reactive secondary minerals on the slag granule surfaces from
      the field filter which were likely created by weathering. This slow weathering
      effect, which generates substantial new adsorption sites, is not accounted for by
      adsorption isotherms rendering them ineffective in slag filter design.

PMID- 19403983
TI  - Effects of telmisartan therapy on metabolic profiles and serum high molecular
      weight (HMW)-adiponectin level in Japanese male hypertensive subjects with
      abdominal obesity.
AB  - AIM: Telmisartan, an angiotensin II receptor blocker (ARB), was reported to have
      partial peroxisome proliferator-activated receptor gamma (PPAR gamma) activity in
      vitro. Also, adipocyte-derived protein adiponectin, especially its high molecular
      weight (HMW) form, has been reported to have beneficial effects on insulin
      resistance and atherosclerosis. We investigated the effects of 3-month
      telmisartan therapy on various metabolic parameters, including serum HMW
      adiponectin and high-sensitivity C-reactive protein (hs-CRP) levels in male
      hypertensive subjects with abdominal obesity. METHODS: This study included 19
      Japanese male hypertensive subjects, aged 51.2+/-7.6 (mean+/-SD) years, and body
      mass index 27.7+/-4.1 kg/m(2). In these subjects, 14 were naive to telmisartan
      treatment (40.0+/-15.7 mg daily), and 5 were changed from other ARBs to
      telmisartan. Serum HMW adiponectin concentration was assayed using HMW-selective
      ELISA kit. RESULTS: In all 19 subjects, systolic/diastolic blood pressure (BP)
      decreased from 153/98 to 134/85 mmHg (p<0.001 for both). Serum HMW-adiponectin
      level increased from 2.06+/-0.81 to 2.40+/-0.96 microg/mL (+16.4%, p=0.017). Body
      weight, glucose, insulin, lipids and hs-CRP did not change during the study
      period, and there were no adverse effects in any subject. In the newly
      administered group (n=14), the results were almost the same: BP decreased from
      155/98 to 134/84 mmHg (p=0.0015 for both), and serum HMW-adiponectin level
      increased from 2.07+/-0.68 to 2.39+/-0.99 microg/mL (+15.5%, p=0.089).
      CONCLUSION: These data suggest that telmisartan therapy is efficient for
      controlling BP, and may exert beneficial effects on HMW adiponectin in male
      hypertensive subjects with abdominal obesity.

PMID- 19403984
TI  - SPARC is a major secretory gene expressed and involved in the development of
      proliferative diabetic retinopathy.
AB  - AIM: Neovascularization is an important event in proliferative diabetic
      retinopathy (PDR), where various secretory proteins including multiple growth
      factors are considered to be involved in this process. We searched for secretory
      proteins expressed in a surgical specimen obtained from the eyes of patients with
      PDR. METHODS: We developed the oligo-cap signal sequence trap (SST) strategy
      which enables us to screen for secretory or membrane proteins from a minimal
      starting material. Using this method, we were able to screen a cDNA library
      constructed from a surgical specimen obtained from the eyes of the patients with
      PDR. RESULTS: Majority of the cloned cDNAs turned out to encode secreted protein
      acidic and rich in cystein (SPARC), strongly suggesting that SPARC is highly
      expressed in PDR. Analysis of vitreous fluid from various patients has shown that
      the concentration of SPARC protein is increased in patients with PDR.
      Furthermore, subretinal injection of recombinant SPARC adenovirus induced PDR
      like changes in the rat eye. CONCLUSIONS: Our results strongly suggested that
      SPARC is involved in the development of diabetic retinopathy (DR).

PMID- 19403985
TI  - Relations between serum reactive oxygen metabolites (ROMs) and various
      inflammatory and metabolic parameters in a Japanese population.
AB  - AIM: Both oxidative stress and inflammation are known to play roles in the
      pathogenesis of cardiovascular disease. We investigated the relations between
      reactive oxygen metabolites (ROMs) and various inflammatory and metabolic
      parameters in a Japanese population. METHODS: We analyzed 48 male and 69 female
      subjects, aged 25 to 65 years, who underwent an annual health checkup in our
      university. Serum ROM level was assayed using a free radical elective evaluator.
      We also measured serum concentrations of high-sensitivity C-reactive protein
      (hsCRP), insulin, and high molecular weight (HMW) adiponectin. RESULTS: Although
      the serum ROM level in females (347+/-83 Carr U) was slightly higher than in
      males (333+/-53 Carr U), this was not statistically significant. In the 48 male
      subjects, the ROM level negatively correlated with age (r=-0.344, p=0.0161), and
      positively correlated with the hsCRP level (r=0.306, p=0.0338). In the 69 female
      subjects, the ROM level negatively correlated with serum creatinine (r=-0.293,
      p=0.0141), and positively correlated with insulin (r=0.278, p=0.0202), the
      insulin resistance index (r=0.286, p=0.0170) and hsCRP levels (r=0.487,
      p<0.0001). Stepwise multiple regression analysis revealed that serum hsCRP,
      creatinine, and age were independently correlated with the serum ROMs level
      (R2=0.365; F value highest for hsCRP). When the study subjects were divided into
      tertiles according to the ROM level, serum hsCRP was significantly different
      among the three groups: its level was highest in the highest tertile of ROMs
      (p<0.001). CONCLUSION: These results suggest that the serum ROM level is closely
      associated with serum hsCRP in Japanese adult subjects.

PMID- 19403986
TI  - Effects of Rosuvastatin on Oxidized-LDL Cholesterol in the Elderly.

PMID- 19403987
TI  - Heparin cofactor II is an independent protective factor against peripheral
      arterial disease in elderly subjects with cardiovascular risk factors.
AB  - AIM: Heparin cofactor II (HCII) specifically inactivates thrombin action at the
      injured vascular wall. We have reported that HCII is a protective factor against
      coronary in-stent restenosis and carotid atherosclerosis; however, it is unclear
      whether there is any correlation between plasma HCII levels and the development
      of peripheral arterial disease (PAD). METHODS: Plasma HCII activity and the ankle
      brachial pressure index (ABI) were determined in 494 elderly subjects with
      cardiovascular risk factors. PAD was diagnosed by ABI below 0.9, and 62 subjects
      were diagnosed with PAD. The relationship between factors that affect
      cardiovascular events and the prevalence of PAD was statistically evaluated.
      RESULTS: Mean HCII activity in PAD subjects was significantly lower than in non
      PAD subjects (87.5+/-19.7% v.s. 94.6+/-17.8%, p=0.009). Multivariate logistic
      regression analysis showed that age (odds ratio [OR]: 1.062, p=0.0016), current
      smoking (OR 3.028, p=0.002) and diabetes mellitus (OR 2.656, p=0.008) were
      independent and progressive determinants of PAD. In contrast, HCII was an
      independent inhibitory factor of PAD (OR: 0.982, p=0.048). CONCLUSIONS: Plasma
      HCII activity is inversely related to the prevalence of PAD. HCII may function as
      the sole protective factor against PAD in elderly people with cardiovascular risk
      factors.

PMID- 19403988
TI  - Smoking confers a MTHFR 677C>T genotype-dependent risk for systemic
      atherosclerosis: results from a large number of elderly autopsy cases that died
      in a community-based general geriatric hospital.
AB  - AIM: We attempted to explore interactions between smoking and the genetic
      polymorphism of 24 atherosclerosis-related candidate genes in systemic
      atherosclerosis. METHODS: The study comprised 1,503 consecutive autopsy cases.
      The male-to-female ratio was 1.16 and the average age at death was 80.3 years.
      Seventy percent of men and 22% of women were current or past smokers. The degree
      of atherosclerosis in 10 arteries was semi-quantitatively assessed. Melting curve
      analysis analyzed 34 single nucleotide polymorphisms (SNPs) of 24 genes. RESULTS:
      Twenty-four SNPs did not interact with smoking on atherosclerosis, while 7 SNPs
      interacted in one artery and 2 SNPs in two arteries. The genotypes of MTHFR
      677C>T and smoking significantly interacted in four arteries, including the
      common carotid artery, common and external iliac arteries, and femoral artery.
      The odds ratios of smoking on atherosclerosis were high (3.034.63) in TT
      homozygotes, intermediate (1.755.24) in heterozygotes, and low (1.752.63) in CC
      homozygotes in systemic arteries except for cerebral and coronary arteries.
      CONCLUSION: MTHFR 677 TT homozygotes are more likely to develop atherosclerosis
      than heterozygotes or CC homozygotes, if they smoke. Thus, smoking cessation is
      more important in the prevention of atherosclerosis in MTHFR 677 TT homozygotes.

PMID- 19403989
TI  - Characteristics of reference intervals of metabolic factors in healthy Japanese:
      a proposal to set generation- and gender-specific diagnostic criteria for
      metabolic syndrome.
AB  - AIM: To verify the clinical diagnostic criteria for metabolic syndrome (MetS
      Criteria) for Japanese (Japanese-Criteria) from the viewpoint of reference
      intervals (RIs) of metabolic factors. METHODS: In healthy subjects selected from
      1,379 males and 1,528 females aged 20-65 years, generation-and gender-specific
      RIs of metabolic factors were determined. Then, from the upper or lower limits of
      the RIs, new MetS-Criteria were tentatively set (New-Criteria). RESULTS: RIs of
      some metabolic factors were associated with gender- and/or generation-specific
      differences. In both genders, the New-Criteria for subjects in their 40s and over
      (older adults) were comparable to the Japanese-Criteria, whereas the New-Criteria
      for these in their 30s and less (younger adults) were not. Levels of cut-off
      values in the New-Criteria for younger adults were mostly between those of the
      Japanese-Criteria and recently established MetS-Criteria for adolescents. The
      prevalence of metabolic syndrome estimated by the Japanese-Criteria and the New
      Criteria well corresponded in older adults but significantly differed in younger
      adults. CONCLUSION: MetS-Criteria prepared on gender- and generation-specific
      bases may be necessary. The Japanese-Criteria, which may still have room for
      minor changes, seem to be valid at least for older adults; however, new MetS
      Criteria should be established for younger adults.

PMID- 19403990
TI  - In addition to insulin resistance and obesity, brachial-ankle pulse wave velocity
      is strongly associated with metabolic syndrome in Chinese--a population-based
      study (Taichung Community Health Study, TCHS).
AB  - AIM: To investigate the association between arterial stiffness (present with
      brachial-ankle pulse wave velocity (baPWV)) and metabolic syndrome (MetS) in a
      population-based study of middle-aged Chinese. METHODS: MetS was defined using
      the AHA/NHLBI criteria. A total of 1,018 subjects aged 40 years and over were
      recruited in 2004. Homeostasis model assessment was applied to estimate the
      degree of insulin resistance (HOMA-IR). The baPWV was divided into four groups by
      quartiles. RESULTS: The prevalence of MetS and its individual components
      increased by the increase in baPWV quartiles. After adjusting for age, BMI, HOMA
      IR, smoking, alcohol drinking, betel nut chewing, and physical activity status,
      multiple logistic regression revealed that baPWV groups were significantly
      associated with MetS. Compared with the lowest baPWV quartile, the adjusted odds
      ratio of having MetS in baPWV quartile II, III, IV was 2.10 (1.034.28), 4.48
      (2.169.26), 10.4 (4.5324.0) in men, and 4.20 (1.4712.0), 14.6 (5.2240.6), 16.3
      (5.4848.2) in women, respectively. The prevalence of MetS increased with the
      increase of age, HOMA-IR, and BMI groups. The optimal cut-off values of baPWV for
      MetS were 1,539 cm/sec in men and 1,482 cm/sec in women, respectively.
      CONCLUSIONS: In addition to insulin resistance and obesity, baPWV was strongly
      related to MetS in middle-aged Taiwan Chinese. The cut-off value of baPWV for
      cardiovascular disease differed between genders.

PMID- 19403991
TI  - Apolipoprotein A-V is a potent modulator of HDL and VLDL components in
      preadolescent children.
AB  - AIM: Mice lacking apolipoprotein A-V (apoA-V) displayed an increase in serum
      triglyceride (TG) levels; however, the correlation of apoA-V levels with TG
      levels in humans is controversial, and the exact mechanism by which apoA-V
      affects TG levels is unclear. The aim of the present study was to clarify the
      impact of apoA-V on the lipoprotein subclass profile in preadolescent children,
      which has not been studied. METHOD: The study subjects were 178 (89 male, 89
      female) 4th grade elementary school children (mean+/-SD: 9.5+/-0.5 years old).
      ApoA-V levels were determined by an enzyme-linked immunosorbent assay, and the
      lipid component of each lipoprotein fraction and their particle sizes were
      measured by HPLC. RESULTS: Levels of apoA-V showed no gender difference in
      preadolescent children, and were not affected by anthropometric variables. ApoA-V
      had a negative association with serum TG levels and TG levels in each lipoprotein
      fraction, and a positive association with HDL-C. In particular, apoA-V appears to
      contribute to the increase in cholesterol levels in the larger HDL fraction.
      CONCLUSIONS: It was suggested that apoA-V is a potent modulator of HDL and VLDL
      components in preadolescent children.

PMID- 19403992
TI  - Effects of eicosapentaenoic acid on endothelial cell-derived microparticles,
      angiopoietins and adiponectin in patients with type 2 diabetes.
AB  - AIM: The aim of this study was to evaluate the significance of endothelial cell
      derived microparticles (EDMP), angiopoietin-2 (Ang-2) and adiponectin in
      hyperlipidemic patients with and without type 2 diabetes mellitus, and to compare
      the two for the effects of eicosapentaenoic acid (EPA) on these markers. METHODS:
      One hundred and twenty-six hyperlipidemic patients with and without type 2
      diabetes mellitus received EPA 1,800 mg daily, and 50 of the patients were non
      diabetic. RESULTS: EDMP and Ang-2 levels prior to treatment were higher in
      diabetic patients than in non-diabetic patients, whereas adiponectin levels were
      lower in diabetics. When diabetic patients were classified into two groups on the
      basis of Ang-2 levels, the levels of all markers remained unchanged in those
      without a high Ang-2 level after EPA treatment. In contrast, all markers except
      for adiponectin were decreased significantly in diabetic patients with high Ang-2
      levels after 6 months of EPA treatment. These diabetic patients with high Ang-2
      levels displayed a more significant increase in adiponectin levels after EPA
      treatment than those who did not. CONCLUSION: These results suggest that EPA
      possesses an adiponectin-dependent anti-atherosclerotic effect and may be
      beneficial for the prevention of vascular complications in diabetic patients with
      high Ang-2 levels.

PMID- 19403993
TI  - Peripheral-type benzodiazepine receptor antagonist is effective in relieving
      neuropathic pain in mice.
AB  - cDNA microarray analysis showed the expression of peripheral-type benzodiazepine
      receptor (PBR) mRNA is slightly enhanced in the spinal cord of mice with spinal
      nerve injury (SNL) as compared with sham-operated mice. PBR transports
      cholesterol to the mitochondria, where cholesterol is converted to pregnenolone.
      Pregnenolone is then metabolized to progesterone, an activator of progesterone
      receptor, and further metabolized to produce allopregnanolone and 3alpha,21
      dihydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THDOC), positive allosteric
      modulators and activators of the GABA(A) receptor. In the present study, we first
      tested whether the enhanced PBR expression is causally related to neuropathic
      pain, and we found that the PBR antagonist PK11195 is effective in reducing SNL
      induced mechanical allodynia and thermal hyperalgesia. Next we tested whether the
      PK11195-induced antinociception is attributable to reduced neurosteroid
      synthesis, which may possibly lead to reduced activation of the progesterone
      receptor and/or GABA(A) receptor. We found that allopregnanolone and
      3alpha,5alpha-THDOC are effective in reducing the anti-hyperalgesic effect of
      PK11195, suggesting a partial contribution of reduced GABA(A)-receptor activation
      to PK11195-induced antinociception.

PMID- 19403994
TI  - Zonisamide increases dopamine turnover in the striatum of mice and common
      marmosets treated with MPTP.
AB  - The effect of zonisamide, an antiepileptic agent with anti-parkinsonian effects,
      was studied on dopamine neurons of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-treated C57 mice and common marmosets. Groups of mice (n = 8 - 9) were
      treated with: MPTP (15 mg/kg every 2 h x4); MPTP plus zonisamide (40 mg/kg
      administered 1 h before each MPTP dose); MPTP plus selegiline (2 mg/kg
      administered 1 h before the first MPTP dose); zonisamide (40 mg/kg x4); and
      saline controls. Groups of common marmosets (n = 4 - 6) were treated with: MPTP
      (2.5 mg/kg every 24 h x3); MPTP plus zonisamide (40 mg/kg administered 1 h before
      each MPTP dose); MPTP plus selegiline (2 mg/kg administered 1 h before the first
      MPTP dose); and saline controls. Brain dopamine and its metabolites were
      determined by HPLC. Dopamine content decreased in the striatum of MPTP-treated
      mice and monkeys. Co-administration of selegiline inhibited the effect of MPTP
      and dopamine contents were similar to those of the controls. Co-administration of
      zonisamide did not inhibit the effect of MPTP on dopamine content, but increased
      striatal dopamine turnover of animals treated with MPTP plus zonisamide more than
      in those treated with MPTP alone. MPTP treatment caused a compensatory increase
      of dopamine turnover in the striatum by remaining neurons. Zonisamide may help
      dopaminergic neurons by increasing striatal dopamine turnover following MPTP
      treatment.

PMID- 19403995
TI  - Anticancer effects of phenoxazine derivatives revealed by inhibition of cell
      growth and viability, disregulation of cell cycle, and apoptosis induction in
      HTLV-1-positive leukemia cells.
AB  - Adult T-cell leukemia (ATL) is a malignant tumor of human CD4(+) T cells infected
      with a human retrovirus, T lymphotropic virus type-1 (HTLV-1). The aim of the
      present study was to investigate the apoptotic effects of phenoxazines, 2-amino
      4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-1), 3-amino-1,4alpha
      dihydro-4alpha,8-dimethyl-2H-phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3
      one (Phx-3) on a T cell leukemia cell line from ATL patients, MT-1 cells; HTLV-1
      transformed T-cell lines, HUT-102 cells and MT-2 cells; and an HTLV-1-negative
      rat sarcoma cell line, XC cells. Among these phenoxazines, Phx-3 at
      concentrations of less than 10 microg/ml extensively inhibited growth and cell
      viability; arrested cell cycles at sub G(0)/G(1) phase; and augmented apoptosis
      of MT-1, HUT-102, and MT-2 cells. However, these phenoxazines did not affect the
      cell viability of an HTLV-1-negative rat sarcoma cell line, XC cells, and
      phytohemaggutinin-activated human peripheral blood mononuclear cells, although
      they markedly inhibited the growth of these cells. The transmission of HTLV-1
      from HTLV-1-positive cells (MT-2 cells) to HTLV-1-negative cells (XC cells) was
      considered to be prevented by Phx-1, Phx-2, or Phx-3 because the syncytium
      formation between these cells was inhibited markedly in the presence of these
      phenoxazines. The present results suggest that Phx-1, Phx-2, and, in particular,
      Phx-3 may be useful as therapeutic agents against ATL, which is extremely
      refractory to current therapies.

PMID- 19403996
TI  - Amelioration of renal ischemia-reperfusion injury by inhibition of IL-6
      production in the poloxamer 407-induced mouse model of hyperlipidemia.
AB  - It is largely unknown whether hyperlipidemia is involved in the pathobiology of
      renal ischemia-reperfusion (I/R) injury that is an important cause of acute
      kidney injury. Here we studied the effect of experimental dyslipidemia on renal
      I/R injury. Renal I/R injury was less severe in hyperlipidemic mice treated with
      poloxamer 407 than in the control mice. Cytokine analyses revealed decreased
      levels of renal and serum IL-6 in the hyperlipidemic mice after renal I/R.
      Protection from renal I/R injury in the hyperlipidemic mice was diminished by
      administration of recombinant IL-6. Concanavalin A-induced IL-6 release from
      cultured splenocytes derived from the hyperlipidemic mice was lower than that
      from splenocytes of normal mice. In hypercholesterolemic apolipoprotein E
      knockout mice, in which renal I/R injury is less severe than in control mice,
      renal I/R-induced IL-6 production was also less than that in controls. In
      angiopoietin-like 3-deficient mice, which were hypolipidemic, renal dysfunction
      and renal IL-6 level after I/R were similar to those of control mice. Our data
      indicate that the presence of experimental hyperlipidemia may be associated with
      a decreased risk of renal I/R injury, possibly mediated by reduced renal IL-6
      production after the insult and extend the notion that an anti-IL6 agent would be
      useful for the treatment of acute kidney injury.

PMID- 19403997
TI  - Rokitamycin induces a mitochondrial defect and caspase-dependent apoptosis in
      human T-cell leukemia Jurkat cells.
AB  - Macrolides are a well-known family of oral antibiotics whose antibacterial
      spectrum of activity covers most relevant bacterial species responsible for
      respiratory infectious disease. In recent years, it has been reported that
      macrolides have not only bactericidal activity but also direct immunomodulating
      activity in mammals. In this study, we observed new physiological activity of
      macrolides and examined whether various macrolides induce apoptosis in human
      leukemia cell lines. We investigated the effects of 13 different macrolides on
      the viability of Jurkat and HL-60 cells. Among all the macrolides used in this
      study, rokitamycin, a semisynthetic macrolide with a 16-member ring, effectively
      induced cell death. Rokitamycin induced DNA fragmentation and caspase activation,
      resembling the progression of apoptosis. Moreover, rokitamycin reduced the
      mitochondrial transmembrane potential and released cytochrome c from mitochondria
      to the cytosol, suggesting that mitochondrial perturbation is involved in
      rokitamycin-induced apoptosis. These results suggest that rokitamycin possesses
      not only bactericidal activity but also pro-apoptotic activity in human leukemia
      cells.

PMID- 19403998
TI  - Demethylation dynamics of the paternal genome in pronuclear-stage bovine zygotes
      produced by in vitro fertilization and ooplasmic injection of freeze-thawed or
      freeze-dried spermatozoa.
AB  - This study was designed to investigate the dynamics of the paternal genome
      demethylation in pronuclear-stage bovine zygotes produced either by in vitro
      fertilization (IVF) or intracytoplasmic sperm injection (ICSI) using freeze
      thawed (FT) as well as freeze-dried (FD) bull sperm stored at +4 or -196 C for
      one year. Zygotes were fixed and immunostained using anti-5-methyl-cytosin at 8,
      10, 14 and 18 h post IVF (hpi) and at 6 and 12 h post ICSI (hpic). In
      conventional IVF-derived zygotes, the overall average of the relative methylation
      (RM; male/female) decreased from 0.92 at 8 hpi to 0.69 at 10 hpi (P<0.05) without
      any additional decrease at 14 and 18 hpi (0.67 and 0.64, respectively; P>0.05).
      This was accompanied by higher proportions of zygotes showing RM<0.6 (45.5, 37.5
      and 38.2% at 10, 14 and 18 hpi, respectively; P<0.05) compared with 3.7% at 8
      hpi. The overall averages of the RM in the FT-ICSI derived zygotes (0.79 and 0.66
      at 6 and 12 hpic, respectively) were similar to those in the corresponding IVF
      derived zygotes (8 and 14 hpi), but a higher proportion of the 6 hpic zygotes
      (37.8%; P<0.05) showed an RM<0.6 compared with the 8 hpi zygotes (3.7%). The
      proportions of FD-ICSI derived zygotes at 12 hpic showing an RM<0.6 (60.6 and
      62.4% for +4 and -196 C storage, respectively) were higher than that of the FT
      ICSI derived zygotes (39.4%; P<0.05). Thus, the bovine paternal genome rapidly
      demethylated within 10 h after IVF and 6 h after ICSI, and the freeze-drying
      and/or the storage process had no adverse effect on demethylation of the paternal
      genome. The extent of demethylation in the pronuclear-stage bovine zygotes was
      moderate, with 0.4< or =RM<0.6.

PMID- 19404000
TI  - Prostaglandin F(2alpha) regulates the nitric oxide generating system in bovine
      luteal endothelial cells.
AB  - The objective of the present study was to elucidate whether luteolytic
      prostaglandin F(2alpha) (PGF) plays roles in regulating the nitric oxide (NO)
      generating system in luteal endothelial cells (LECs). Reverse transcriptase PCR,
      immunoblotting and immunostaining revealed the presence of PGF receptor mRNA (521
      bp) and protein (64 kDa) in cultured LECs obtained from the mid-stage corpus
      luteum. When cultured LECs were exposed to 0.1 microM-10 microM PGF, NO
      production was significantly stimulated by PGF at 24 h. When LECs were exposed to
      1 microM PGF for 2, 6 and 24 h, PGF did not affect the expressions of endothelial
      NO synthase (eNOS) mRNA and protein. On the other hand, PGF stimulated the
      expression of inducible NOS (iNOS) mRNA (P<0.05) and protein (P<0.05) at 2 h, but
      not at 6 and 24 h. By observing the conversion of [(3)C](L)-arginine to [(3)C](L)
      citrulline, we found that PGF stimulated NOS activity in cultured LECs at 2 h
      (P<0.05). The overall findings indicate that bovine LECs are a target for PGF and
      that PGF stimulates iNOS expression and NOS activity in bovine LECs. Stimulation
      of the NO generating system and NOS activity by PGF may result in increasing
      local NO production followed by luteolysis.

PMID- 19403999
TI  - Lysophosphatic acid modulates prostaglandin secretion in the bovine endometrial
      cells differently on days 8-10 of the estrous cycle and early pregnancy.
AB  - Lysophosphatidic acid (LPA) is becoming a new player in regulation of the
      reproductive processes of domestic animals. In the present study, we examined
      whether LPA modulates prostaglandin (PG) synthesis in the bovine endometrium at
      the time of the early maternal pregnancy recognition compared with the respective
      days of the estrous cycle and the enzymatic mechanism of this action. Bovine
      epithelial and stromal endometrial cells isolated from the uteri on days 8-10 of
      the estrous cycle and pregnancy were cultured with LPA for 24 h. LPA increased
      PGE(2) production in stromal cells during the estrous cycle and early pregnancy.
      On days 8-10 of pregnancy, LPA inhibited PGF(2alpha) production in epithelial
      cells. LPA stimulated PGES mRNA expression in stromal cells during both examined
      phases and inhibited PGFS mRNA expression in epithelial cells on days 8-10 of
      pregnancy. The overall results indicate that LPA may serve as a luteotropic
      factor during the luteal phase of the estrous cycle and early pregnancy
      stimulating PGE(2) synthesis and mRNA expression for PGES in stromal cells.
      Moreover, during early pregnancy, LPA might protect bovine CL and early embryo
      development by decreasing PGF(2alpha) synthesis and mRNA expression for PGFS in
      the epithelial cells of the bovine endometrium.

PMID- 19404001
TI  - Early presence of immune cells in the developing gonad of the gilthead seabream
      (Sparus aurata Linnaeus, 1758).
AB  - A great deal is known regarding the process of sex differentiation in fish.
      However, little is known about the presence of immune cells and cytokines in this
      process. In the gilthead seabream, both immune cells and cytokines play an
      important role in the tissue reorganization of the gonads during the adult
      reproductive cycle. We have studied, using light microscopy and
      immunocytochemistry, the ontogenetic development of the gilthead seabream gonads,
      focusing on the presence of immune cells and cytokines. We show that the
      testicular area is quickly differentiated and becomes functional in specimens
      less than a year old, while the ovarian area differentiates later and continues
      to develop during the first two years of life. Throughout the morphogenesis
      process, acidophilic granulocytes were present in the gonad. Interleukin-1b
      (Il1b) is produced in the testicular area in juveniles and male fish, but not in
      the ovarian area. Macrophage-colony stimulating factor receptor (Mcsfr) is not
      produced in the undifferentiated gonad and is only found once the testicular area
      is well developed.

PMID- 19404002
TI  - Effect of vanadate on the chromatin configuration in pig GV-oocytes.
AB  - Vanadate, an inhibitor of tyrosine phosphatases, has been reported to prevent
      germinal vesicle breakdown in mammalian oocytes. We examined the effect of
      vanadate on the chromatin configuration of fully grown pig oocytes. In the
      presence of human menopausal gonadotropin (hMG), vanadate (0.5-5 mM) resulted in
      a dose-dependent change in oocyte chromatin in germinal vesicles from the
      condensed state to a decondensed filamentous or stringy configuration. The effect
      of vanadate and hMG on chromatin configuration could be replicated with 2 mM
      dibutyryl cyclic AMP (dbcAMP) in place of hMG. Western blot analysis showed that
      vanadate caused a massive accumulation in the oocytes of tyrosine-phosphorylated
      proteins with a range of molecular weights that was enhanced by both hMG and
      dbcAMP in a similar manner. These results suggest that inhibition of tyrosine
      phosphatase(s) in the presence of an effective level of cAMP induces a change in
      chromatin configuration of pig oocytes.

PMID- 19404003
TI  - Plasma and fecal sex steroid hormone profiles during the estrous cycle in a
      Japanese serow (Capricornis crispus).
AB  - We aimed to determine plasma progesterone and estradiol-17beta concentrations, as
      well as fecal progesterone concentrations during the estrous cycle in a female 8
      year-old Japanese serow (Capricornis crispus). The step frequencies during the
      night were recorded by a pedometer attached to the serow's hind leg from October
      to the following June. Estrous behavior was also monitored during the day. Blood
      samples were taken once a day from 8 February to 10 March from an indwelling
      catheter placed in the jugular vein. Fecal samples were taken once or twice a day
      from 1 January to 29 April. Plasma and fecal progesterone and plasma estradiol
      concentrations were determined using time-resolved fluoroimmunoassays. The estrus
      behavior observed lasted for 2-3 days. Peak step frequencies were recorded
      between November and April, at intervals of 17-19 days. Plasma progesterone
      concentrations remained elevated (1-7.7 ng/ml) for 12 days during non-estrus, and
      plasma estradiol concentrations were highest when the peak step frequency and
      estrous behavior were observed. Step frequency increased around the times fecal
      progesterone levels fell to basal levels. Progesterone concentrations in feces
      were significantly correlated with those in sera. Thus, measurement of fecal
      progesterone concentrations might be useful for monitoring the reproductive
      status of the Japanese serow.

PMID- 19404004
TI  - [Application of NFkappaB inhibitor for arthritis].
AB  - Recent progress in DNA technologies has provided the strategies to regulate the
      transcription of disease-related genes in vivo using antisense
      oligodeoxynucleotide (ODN). Transfection of cis-element double-stranded
      oligodeoxynucleotides (decoy ODNs) has been reported as a new therapeutic tool of
      anti-gene strategies for gene therapy. In the field of arthritis, decoy ODNs
      strategies have been significant therapeutic potential. The concept of regulation
      the disease related gene expression at the level of transcriptional factor may be
      more therapeutic effects compared with monotherapy in arthritis. Injection of
      NFkappaB decoy ODN into the affected joint resulted in marked suppression of
      joint destruction in CIA models. In vitro studies demonstrated that the
      inhibitory effect on inflammatory cytokines and matrix metalloproteinase
      production from stimulated synovial cells derived from rheumatoid arthritis
      patients. NFkappaB decoy ODN inhibited induction of osteoclasts and bone
      resorption ability. Parthenolide is one of the main sesquiterpense lactones
      responsible for the bioactivities of feverfew and recently reported to inhibit
      NFkappaB activation. Parthenolide has ameliorated the severity of joint
      destruction in experimental animal model. Based upon these findings, NFkappaB may
      be one of important therapeutic target for arthritis.

PMID- 19404005
TI  - [Imatinib].
AB  - The progress in molecular targeting therapy includes two tides, namely, small
      molecule compounds and large molecule biological agents. Although the latter
      prevails in the field of clinical immunology, the former attracts more and more
      attention in these few years. Most of molecular targeting small compounds are the
      inhibitors of tyrosine kinases, including pioneering imatinib which inhibits the
      receptor for platelet-derived growth factor (PDGF), c-Abl, etc. The therapeutic
      concentrations of imatinib almost completely abrogated the morphological
      alteration and proliferation of fibroblastic cells induced by PDGF stimulation in
      3-dimensional culture system in vitro. Indeed, imatinib has been shown to be
      effective in various animal disease models for arthritis, interstitial pneumonia,
      glomerulonephritis, and pulmonary hypertension. Furthermore, its efficacy in
      patients with systemic sclerosis has been recently reported from several
      institutes. Since established treatments had not been found for fibrotic lesion
      before, imatinib, a dual inhibitor of both transforming growth factor beta-, and
      PDGF-signaling, is likely to be a potent drug against fibrosis. Its efficacy and
      safety in fibrotic and immune-mediated diseases, such as systemic sclerosis, are
      currently under investigation throughout the world.

PMID- 19404006
TI  - Jak inhibitor ; possibility and mechanism as a new disease modifying anti
      rheumatic drug.
AB  - Treatment of rheumatoid arthritis (RA) has developed dramatically by the
      appearance of biologics. However the development of a new anti-rheumatic drug is
      necessary because of its issue on route of administration and expense. Recently,
      inhibitors targeting tyrosine kinase known as Janus kinase (Jak) has shown
      prominent effect on RA. Jak family is comprised by Jak1, Jak2, Jak3 and Tyk2
      which is necessary for signal transduction for inflammatory cytokines. INCB18424
      targeting Jak1/2 and CP690,550 targeting Jak3 has been developed and is now on
      phase II clinical study for RA. Results from those clinical studies have proven
      that these inhibitors can be effective as biologics with few side effects.
      However, it has been reported that inhibitors are less specific than it has been
      expect and that non-specificity can be important for its effect. Therefore, we
      think that the mechanism of inhibitors cannot be explained by its inhibition of a
      single kinase. Herein, we describe IL-10 overproduction by Jak3 and Stat6
      deficient dendritic cell. We speculate that this is one possible mechanism of
      action for CP690,550 although as for its non-specificity we need further
      investigation to predict not only its effect but also its side effect in a long
      term administration.

PMID- 19404007
TI  - [A new therapeutic approach for autoimmune diseases by the sphingosine 1
      phosphate receptor modulator, fingolimod (FTY720)].
AB  - Fingolimod (FTY720) is the first of a new immunomodulator class : sphingosine 1
      phosphate (S1P) receptor modulator. We have found FTY720 by chemical modification
      of a natural product, myriocin derived from Isaria sinclairii, a kind of
      vegetative wasp. FTY720 has shown to be highly effective in experimental
      allograft models and autoimmune disease models. A most striking feature of FTY720
      is the induction of a marked decrease in peripheral blood lymphocytes at doses
      that show immunomodulating effects in these models. It is revealed that the
      reduction of circulating lymphocytes by FTY720 is due to sequestration of
      lymphocytes into secondary lymphoid organs and thymus. FTY720 is rapidly
      converted to FTY720-phosphate (FTY720-P) by sphingosine kinases. FTY720-P acts as
      a potent agonist at S1P receptor type 1 (S1P(1)), internalizes S1P(1) on
      lymphocytes, and inhibits the migration of lymphocytes toward S1P. Thus, it is
      highly likely that immunomodulating effects of FTY720 are caused by inhibition of
      S1P/S1P(1)-dependent lymphocyte egress from secondary lymphoid organs and thymus.
      Since FTY720 possesses a novel mechanism of action and is reported to be highly
      effective in multiple sclerosis patients, it is presumed that FTY720 provides a
      new therapeutic approach for autoimmune diseases including multiple sclerosis.

PMID- 19404008
TI  - [Diagnostic utility of anti-cyclic citrullinated peptide antibody in early
      rheumatoid arthritis].
AB  - Current therapeutic strategies against rheumatoid arthritis (RA) employ
      increasingly aggressive regimens from an early stage of the disease ; thus,
      serological markers more specific than IgM-rheumatoid factor (IgM-RF) are
      desirable. Anti-cyclic citrullinated peptide (anti-CCP) antibody has been
      reported as a useful and highly specificity marker for the diagnosis of RA. To
      clarify the diagnostic utility of anti-CCP antibody in early RA, we measured
      serum concentrations of anti-CCP antibody, IgM-RF, anti-agalactosyl IgG antibody
      and matrix metalloproteinase (MMP)-3 in 184 polyarthritis patients who showed
      onset symptoms within the previous 2 years. The diagnostic sensitivity of anti
      CCP antibody in early RA was 60.0%, equivalent to IgM-RF (66.3%) and anti
      agalactosyl IgG antibody (66.0%). Specificity, positive predictive values and
      diagnostic accuracy of anti-CCP antibody were the best among the four tested
      makers. In 38 patients who initially did not meet the ACR criteria for RA, but
      were diagnosed with RA during the course, the diagnostic sensitivity of anti-CCP
      antibody was 55.3%. On the other hand, the disease activity score (DAS) 28 of
      anti-CCP antibody positive and the negative patients was 5.16 and 5.34,
      respectively. Our data indicated that determination of anti-CCP antibody was
      useful for early diagnosis of RA.

PMID- 19404009
TI  - [A case of systemic lupus erythematosus complicated with autoimmune hepatitis and
      thrombotic thrombocytic purpura].
AB  - A 51-year-old woman was admitted to our hospital because of systemic jaundice,
      general fatigue in August 24, 2007. She was diagnosed with systemic lupus
      erythematosus (SLE) as a result of a discoid rash, photosensitivity,
      lymphocytopenia, elevated serum anti ds-DNA antibody and a positive test for
      antinuclear antibody. Her laboratory data revealed severe liver dysfunction,
      suggesting autoimmune hepatitis (AIH). She was also diagnosed with thrombotic
      thrombocytic purpura (TTP) because of thrombocytopenia, hemolytic anemia, renal
      dysfunction and decreased ADAM-TS13 activity. The patient was treated by
      methylprednisolone pulse therapy, fresh frozen plasma infusion and
      ursodeoxycholic acid. Her symptoms and laboratory data rapidly improved and a
      liver biopsy was carried out. Interface hepatitis and lymphocyte infiltration
      were observed in the specimen. A diagnosis of definite AIH was made from her
      International AIH group score of 20 points. AIH and TTP are rare complications of
      SLE. The prevalence of the complication of SLE and AIH has been reported as 1.7
      approximately 2.7%, and that of SLE and TTP as 1 approximately 4%. We reported
      here a rare case of SLE complicated with AIH and TTP.

PMID- 19404010
TI  - [Hemophagocytic syndrome in late-onset SLE patients].
AB  - We report two elderly male patients with hemophagocytic syndrome (HPS) associated
      with systemic lupus erythematosus (SLE). They were admitted to the hospital
      because of general malaise. At admission, they showed fever of unknown origin and
      hematological abnormalities without typical symptoms for SLE such as arthralgia
      or malar rash. Chest X-rays, computed tomography and cardiac sonogram
      demonstrated unilateral pleural and pericardial effusions. Bone marrow aspiration
      revealed hypocellular marrow with increased macrophages phagocytosing blood cells
      in the both cases. One patient had positive reactivity for direct Coombs's test
      and high level of platelet-associated antibody, whose symptoms were ameliorated
      only by 20 mg per day of prednisolone. The other patient, however, progressive
      worsened and died regardless of intensive treatment containing methyl
      prednisolone pulse therapy. Late-onset lupus (LO-SLE) patients tend to have a
      more insidious onset of disease, and less frequently show typical symptoms of
      early-onset SLE such as malar rash. So it seems to be important that clinicians
      make a fast diagnosis and proper treatment for LO-SLE and associated HPS by
      careful observation for the latent symptoms and laboratory findings.

PMID- 19404011
TI  - [A case of chronic graft-versus-host disease presenting with polymyositis].
AB  - Polymyositis is an uncommon manifestation as a complication of chronic graft
      versus-host disease (GVHD). We report a case of a 55 years' old woman diagnosed
      as polymyositis 2 years after bone marrow transplantation against T-cell
      lymphoma. Muscle weakness and the elevation of CPK value were compatible with
      pathognomonic findings of polymyositis. However, the muscle weakness was
      distributed particularly into distal lower extremities and neck. It is different
      from that of the typical findings in autoimmune polymyositis. Histological
      findings showed atrophy and anisocytosis of muscles without invasion of
      mononuclear cells. This might be a case of GVHD-induced polymyositis occurring
      symptomatically after substantially progressing under the treatment with
      immunosuppressive agents to control chronic GVHD after bone marrow
      transplantation. The treatment with prednisone (1 mg/kg) brought the rapid
      improvement of muscle weakness and CPK value as well as mouth dryness and
      cholestatic liver dysfunction like in primary biliary cirrhosis. Moreover, dose
      up of cyclosporine and addition of mizolibine allowed for the use of lower dose
      of prednisone. This case suggested that the mononuclear cells invasion into
      muscles in a chronic GVHD patient could not always be a definitive finding of
      chronic GVHD-associated polymyositis because of prior use of immunosuppressive
      agents.

PMID- 19404012
TI  - [A case of polymyalgia rheumatica where a complication of large-vessel vasculitis
      was diagnosed by FDG-PET].
AB  - The patient was a 74-year-old female presenting with abrupt onset of fever and
      proximal muscle pains. She had been diagnosed with polymyalgia rheumatica (PMR).
      On physical examination, there was no tenderness or dilatation of the temporal
      artery and ocular fundi were normal. 18F-FDG-PET revealed accumulation of FDG in
      the aorta as well as in the bilateral subclavian arteries, which strongly
      suggested inflammation of the large blood vessels. Magnetic resonance angiography
      disclosed stenosis of the bilateral subclavian arteries, which was consistent
      with angitis. This case was considered to have developed PMR at an old age with
      positive HLA DR4, and to have a complication large-vessel giant cell arteritis
      (LV-GCA). Administration of prednisolone at a dose of 20 mg/day promptly relieved
      the fever and the myalgia as well. It is difficult to diagnose GCA in PMR if no
      tenderness or dilatation of the temporal artery is present. FDG-PET is considered
      useful, not only for exploration of tumors, but also for evaluation of
      inflammation of large vessels.

PMID- 19404013
TI  - [Picture in clinical hematology no. 36: Case of primary effusion lymphoma with
      severe pericardial effusion].

PMID- 19404014
TI  - [Review of changes introduced by the new WHO classification (4th edition) of
      lymphoid malignancies. An overview].

PMID- 19404015
TI  - [Acute lymphoblastic leukemia].

PMID- 19404016
TI  - [Mature B-cell neoplasms].

PMID- 19404017
TI  - [Mature T- and NK cell neoplasms].

PMID- 19404018
TI  - [Hodgkin lymphoma].

PMID- 19404019
TI  - [Immunodeficiency-associated lymphoproliferative disorders, histiocytic and
      dendritic cell neoplasms].

PMID- 19404020
TI  - [Importance of dose intensity in chemotherapy--lessons from adjuvant chemotherapy
      for early breast cancer].

PMID- 19404021
TI  - [Histone modification: a new era of targeting epigenetics].

PMID- 19404022
TI  - [Multiple myeloma relapsed or progressed as plasmacytoma after allogeneic reduced
      intensity stem cell transplantation: report of three cases].
AB  - Autologous peripheral blood stem cell transplantation (auto-PBSCT) is considered
      the standard therapy for younger patients with multiple myeloma, however,
      survival curve doesn't reach plateau. On the other hand, allogeneic reduced
      intensity stem cell transplantation (RIST) with graft-versus-myeloma (GVM)
      effects is expected to be the curable therapy. We had three cases received RIST
      (one case as a salvage therapy for relapse after tandem auto-PBSCT, and two cases
      as an intentional RIST after achieving partial response by auto-PBSCT). All of
      three cases relapsing or progressing after RIST showed disease type of
      plasmacytoma without plasma cells in the bone marrow. That may be because
      conditioning regimen doesn't include total body irradiation, or GVM is
      ineffective in plasmacytoma, but effective in bone marrow. Here, we report
      clinical course of these three cases with some consideration.

PMID- 19404023
TI  - [Analysis of plasma concentration of thalidomide in Japanese patients of multiple
      myeloma with renal dysfunction].
AB  - The serum concentration of thalidomide in multiple myeloma (MM) patients with
      renal insufficiency has not been investigated in Japan. We examined the serum
      concentration of thalidomide 12 and 16 hours after administration in 5 patients
      with MM (one with normal renal function and four with renal insufficiency,
      including one on hemodialysis (HD)) taking 100-200 mg/day. Concentrations 12 and
      16 hours after administration corresponded to those before and after HD,
      respectively, in the patient on HD. The thalidomide concentration was not
      significantly increased by renal insufficiency. We could not detect any
      correlation between the concentration of thalidomide and its clinical effect.
      Since the elimination of thalidomide during HD seems to be greater than during
      the same period on a non-HD day, it was suggested that thalidomide could be
      eliminated by HD. The concentrations 12 hours after administration were similar
      with or without HD. From these results, even in Japanese patients, the
      thalidomide dosage need not be modified for renal insufficiency and HD.

PMID- 19404024
TI  - [Bacillus cereus sepsis and subarachnoid hemorrhage following consolidation
      chemotherapy for acute myelogenous leukemia].
AB  - A 64-year-old man with acute myelogenous leukemia (FAB classification, M7) in
      remission received consolidation chemotherapy with mitoxantrone/cytosine
      arabinoside. WBC counts decreased to 0/microl on day 14, and fever (39.3 degrees
      C) and epigastralgia developed on day 15. Cefozopran was instituted for febrile
      neutropenia; however, on day 16, he was found to be in cardiac arrest. CT scan on
      day 16 revealed subarachnoid hemorrhage. Gram-positive rods were isolated from
      blood cultures on day 15, and were later identified as B.cereus. He recovered
      transiently, but eventually died on day 19. Postmortem examination demonstrated
      many colonies of B. cereus in the cerebrum, cerebellum, lung, and liver.
      Hepatocyte necrosis was also observed in the liver. Bacterial aneurysms or septic
      emboli were not identified in the arachnoid vessels, but necrosis of cerebral
      vessels was prominent, which was considered to be the cause of subarachnoid
      hemorrhage. Fatal subarachnoid hemorrhage has been reported to be associated with
      B. cereus sepsis, which developed at nadir following chemotherapy for leukemia
      patients. Because of the aggressive clinical course of B. cereus sepsis,
      including the risk for subarachnoid hemorrhage, early treatment with effective
      antibiotics for B. cereus sepsis would be important in the management of leukemia
      patients after chemotherapy.

PMID- 19404025
TI  - [Serum sickness induced by rituximab infusion; report of two cases with
      hematological malignancies].
AB  - We report 2 cases of serum sickness after rituximab infusion. Case 1 is a patient
      with Waldenstrom's macroglobulinemia, and case 2 is a patient with marginal-zone
      B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type and Sjogren's
      syndrome. Both patients had polyclonal hypergammaglobulinemia, were treated with
      rituximab monotherapy, developed serum sickness between 9 and 17 days after the
      first rituximab infusion, developed fever and arthralgia, and improved soon after
      corticosteroid treatment. Serum sickness after rituximab treatment for
      hematological malignancies is very rare as far as we know. We identified three
      risk factors of serum sickness after rituximab infusion from previous reports and
      our cases; administration of rituximab alone, the existence of Sjogren's
      syndrome, and polyclonal hypergammaglobulinemia.

PMID- 19404026
TI  - [Lymphoplasmacytic lymphoma with a breast tumor and IgG+IgA type biclonal
      gammopathy].
AB  - An 88-year-old female was admitted to our hospital due to a right breast tumor
      and biclonal gammopathy (IgG-lambda and IgA-lambda). CT scan showed systemic
      lymphadenopathy. Tumor specimens were comprised of medium-sized atypical
      lymphocytes. Lymphoepithelial lesions and plasmacytic differentiation were
      observed. The atypical lymphocytes were positive for CD20, CD79a, Bcl-2, CD5 and
      negative for CD10, Cyclin D1. Moreover, the cells expressed IgG-lambda or IgA
      lambda. We diagnosed the patient's disease as lymphoplasmacytic lymphoma (LPL).
      Although biclonal gammopathy with IgM elevation has been reported in LPL
      patients, this is the first case of IgG+IgA type biclonal gammopathy.

PMID- 19404029
TI  - [The relationship of microalbuminuria with left ventricular functions and silent
      myocardial ischemia in asymptomatic patients with type 2 diabetes].
AB  - OBJECTIVES: Recently, microalbuminuria (MA), a marker of advanced renal failure,
      has been shown to be related with cardiovascular disease especially in diabetic
      patients. This study was designed to investigate the relationship between MA and
      left ventricular functions and silent myocardial ischemia documented by exercise
      test in patients with type 2 diabetes mellitus. STUDY DESIGN: The study included
      50 asymptomatic patients (36 women, 14 men; mean age 63+/-7 years) with type 2
      diabetes. All the patients underwent treadmill test and biochemical tests
      following transthoracic echocardiography. Microalbuminuria was diagnosed from a
      24-hour urine sample on two different days and the patients were evaluated in two
      groups based on the presence (= or >30 mg/dl) or absence (<30 mg/dl) of MA.
      RESULTS: Twelve patients (24%) were found to have MA. There were no significant
      differences between patients with and without (n=38; 76%) MA with regard to age,
      sex, blood pressure, cardiovascular risk factors, plasma glucose, cholesterol,
      and triglyceride levels, and parameters of renal function (p>0.05). The duration
      of diabetes was significantly longer in patients with MA (p=0.03).
      Echocardiographic findings showed no significant differences in left ventricular
      systolic and diastolic functions between patients with and without MA (p>0.05).
      Exercise test revealed ischemic changes in 21 patients (42%). The incidence of
      silent myocardial ischemia was significantly higher among patients with MA (9/12
      and 75% vs. 12/38 and 31.6%, p<0.001). CONCLUSION: Our data suggest that MA can
      be used as an important marker for coronary artery disease in patients with
      diabetes mellitus.

PMID- 19404030
TI  - [Assessment of the relationship between silent myocardial ischemia,
      microalbuminuria, and left ventricular function in asymptomatic subjects with non
      insulin dependent diabetes mellitus].

PMID- 19404028
TI  - Moderate and heavy alcohol consumption among Turks: long-term impact on mortality
      and cardiometabolic risk.
AB  - OBJECTIVES: The impact of alcohol consumption on various outcomes was
      prospectively evaluated in the participants of the Turkish Adult Risk Factor
      Study. STUDY DESIGN: A total of 3,443 men and women (mean age 47.6+/-12 years)
      were included at baseline and followed-up for a mean of 7.4 years (range 5 to 9
      years). Alcohol drinking status was assessed as abstention and brackets of
      moderate and heavy intake. Only 19.5% of adults (35% of men and 4.2% of women)
      reported consumption of alcohol. In each multivariate analysis, individuals with
      the examined endpoint at baseline were excluded, and alcohol drinking status was
      adjusted for age, sex, smoking status, and physical activity. RESULTS: Alcohol
      intake increased overall mortality (by 2-fold) in men drinking heavily, but not
      in men drinking moderately, nor in women. Heavy drinking in combined sexes
      predicted the risk for incident coronary heart disease (CHD) (RR 2.3; 95% CI
      1.30; 4.05), while moderate drinking tended to be protective (RR 0.72; 95% CI
      0.50; 1.035). Heavy intake predicted incident diabetes risk (RR 2.13) and tended
      to be so for new metabolic syndrome (MetS) in men (RR 1.71), whereas moderate
      alcohol intake was not significantly associated with subsequent development of
      diabetes or MetS and the risk for MetS was reduced in women (p=0.10). CONCLUSION:
      Risk of alcohol intake depends on the amount used: heavy intake raising the risk
      for diabetes and CHD in combined sexes, and overall mortality in men, contrasted
      to moderate intake reducing (borderline) the CHD risk and marginally reducing all
      cause mortality. Risk for MetS tends to be reduced in women alone.

PMID- 19404031
TI  - The influence of dipper and nondipper blood pressure patterns on left ventricular
      functions in hypertensive patients: a tissue Doppler study.
AB  - OBJECTIVES: We investigated the effect of dipper and non-dipper blood pressure
      patterns on left ventricular diastolic filling parameters in hypertensive
      patients. STUDY DESIGN: Fifty-five hypertensive patients (37 women, 18 men; mean
      age 55+/-10 years) were evaluated with echocardiography and ambulatory 24-hour
      blood pressure monitoring. All the patients received antihypertensive drug
      therapy for at least three months prior to the evaluations. Tissue Doppler
      derived systolic and diastolic parameters were compared. RESULTS: Dipper and
      nondipper blood pressure patterns were found in 22 patients (40%) and 33 patients
      (60%), respectively. Both groups had similar left ventricular systolic and
      diastolic diameters. Dipper patients had significantly lower values for left
      atrial diameter (p<0.0001), interventricular septum (p=0.001) and posterior wall
      (p=0.012) thickness, left ventricular mass (p=0.017) and mass index (p=0.021).
      Both groups had similar mitral E and A waves, E/A ratio, E-wave deceleration
      time, isovolumetric relaxation time, and tissue Doppler-derived A' wave. Dipper
      patients had a significantly lower E/E' ratio (10.8+/-3.4 vs. 14.1+/-3.6;
      p=0.002) and significantly higher systolic (S') (p=0.05) and early diastolic (E')
      (p=0.027) tissue velocities. Based on the E/E' ratios being <15 or = or >15, the
      frequency of dipper hypertension was significantly higher in patients with E/E'
      <15 (48.8% vs. 9.1%; p=0.019). The frequency of dippers was also higher among
      patients having an E/E' ratio of <8, compared to those having an E/E' ratio of =
      or >8 to <15 (90% vs. 35.3%; p=0.019). CONCLUSION: Nondipper blood pressure
      pattern may be associated with increased left ventricular mass, impaired left
      ventricular systolic and diastolic dysfunction, and higher left ventricular
      filling pressures.

PMID- 19404032
TI  - [Compensatory hemodynamic variations for cardiovascular stabilization in complete
      atrioventricular block before and after pacemaker implantation].
AB  - OBJECTIVES: Stabilization of the cardiovascular system is maintained by
      variations in hemodynamic and hormonal parameters in complete atrioventricular
      (AV) block. We investigated the variations in hemodynamic parameters and brain
      natriuretic peptide (BNP) levels before and after permanent pacemaker
      implantation for complete AV block. STUDY DESIGN: We evaluated 25 patients (14
      men, 11 women; mean age 72+/-10 years; range 39 to 83 years) who presented with a
      complaint of syncope due to complete AV block. All the patients were
      hemodynamically stable on presentation and were monitored in the coronary care
      unit until permanent pacemaker implantation. Variations in the cardiovascular
      system were determined before and two weeks after pacemaker implantation,
      including mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO),
      systemic vascular resistance (SVR), systemic aortic compliance (SAC), and BNP
      levels. RESULTS: The mean heart rates were 36+/-6 beat/min and 65+/-10 beat/min
      before and after pacing, respectively. Compared to the pacing period, CO was
      significantly lower (p<0.001) and SVR was significantly higher (p=0.001) before
      pacemaker implantation, suggesting a compensatory rise in SVR. The mean arterial
      pressure did not show a significant difference and remained within normal ranges
      before and after pacing. There were no significant differences in SV, SAC, and
      BNP levels before and after pacemaker implantation, with BNP exhibiting increased
      levels in both periods. CONCLUSION: While no compensatory alterations occur in
      SV, SAC, and BNP before and after pacemaker implantation, decreased CO in
      complete AV block seems to be balanced by increased SVR, which results in
      maintenance of MAP within the normal range.

PMID- 19404033
TI  - [The diagnostic value of N-terminal B-type natriuretic peptide in diastolic heart
      failure: comparison with echocardiographic findings].
AB  - OBJECTIVES: We investigated the value of N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) to diagnose diastolic heart failure (DHF) without left
      ventricular (LV) hypertrophy. STUDY DESIGN: The study included 33 patients (17
      males, 16 females) with DHF, who had acute pulmonary congestion and LV ejection
      fraction (EF) >50% on admission, and were stable for at least six months of
      follow-up. The control group consisted of 18 hypertensive patients (9 males, 9
      females) without cardiac symptoms, whose LV mass indices matched the study group,
      and EF was >50%. Plasma NT-proBNP levels were measured and all patients were
      evaluated by echocardiography to examine the relationship between NT-proBNP
      levels and the ratio of peak early diastolic mitral velocity to peak early
      diastolic mitral annular velocity (E/E'). RESULTS: NT-proBNP levels were
      significantly increased in the DHF group (293.4+/-52.1 pg/ml vs. 123.1+/-23.5
      pg/ml, p=0.043). Concerning the severity of diastolic dysfunction and NT-proBNP
      levels, patients with delayed relaxation (n=24) did not differ from the controls,
      whereas those with pseudonormal (n=5) and restrictive (n=4) forms had
      significantly elevated NT-proBNP levels (p=011). In ROC analysis, an NT-proBNP
      level of = or >490 pg/ml predicted DHF with 40% sensitivity and 94% specificity.
      The mean E/E' values were 5.4, 15.4, and 17.6 in patients with delayed
      relaxation, pseudonormal, and restrictive forms, respectively. When all the
      patients were examined in three groups according to the E/E' values (E/E'<8;
      E/E'=8-15; E/E'>15), those having E/E' >15 had significantly higher NT-proBNP
      levels (p=0.0001). There was a highly significant relationship between E/E' and
      NT-proBNP (r=0.761, p=0.001). In ROC analysis, a threshold of 269.1 pg/ml for NT
      proBNP predicted E/E' >15 with 90% sensitivity and 73% specificity. In logistic
      regression analysis, left atrial diameter (p=0.018) and E/E' (p=0.05) were
      independent factors affecting the NT-proBNP level. CONCLUSION: Plasma NT-proBNP
      levels are elevated in DHF independently from LV hypertrophy. NT-proBNP levels
      provide estimation of LV end-diastolic pressure in symptomatic hypertensive
      patients with preserved systolic LV function.

PMID- 19404034
TI  - Aneurysm of the right atrial appendage in an elderly patient.
AB  - A 72-year-old male patient presented with a complaint of pain in both legs during
      short walks of less than 50 meters. Physical examination showed weak arterial
      pulses in both lower extremities. Electrocardiographic and telecardiographic
      evaluations were normal. A previous abdominal ultrasonography examination
      performed for abdominal pain showed an abdominal aortic aneurysm. Coronary
      angiography findings were normal; however, peripheral angiography showed an
      abdominal aortic aneurysm and extensive critical bilateral peripheral artery
      disease. Transthoracic echocardiography disclosed an aneurysmal structure
      neighboring the right atrium. Transesophageal echocardiography demonstrated a
      30x18-mm chamber suggestive of a right atrial appendage aneurysm. Cardiac
      magnetic resonance imaging confirmed the presence of the right atrial appendage
      aneurysm, 25x15 mm in size, over the tricuspid valve. The neck of the aneurysm
      was 11 mm. The patient underwent surgery which included grafting of the abdominal
      aorta and aortobifemoral bypass. He was discharged uneventfully on oral
      anticoagulant therapy.

PMID- 19404035
TI  - Superior vena cava syndrome arising from subclavian vein port catheter
      implantation and paraneoplastic syndrome.
AB  - Central venous thrombosis is an important complication of venous catheterization.
      We presented a 49-year-old male patient who developed massive central venous
      thrombosis causing superior vena cava (SVC) syndrome after placement of a right
      subclavian vein port catheter. The patient had inoperable gastric cancer for
      which he had been receiving chemotherapy for two years. He had a six-month
      history of fixed port catheter placement into the right subclavian vein. Contrast
      enhanced computed tomography (CT) of the chest showed complete obstruction of the
      SVC and CT angiography showed extensive thrombosis from the subclavian vein to
      the end of the SVC. Extensive lung and mediastinal metastases were also observed.
      Surgical intervention was not considered. Fibrinolytic therapy was instituted
      with 75 mg tissue plasminogen activator (tPA) infusion for 18 hours. The
      patient's symptoms and the signs of SVC syndrome disappeared and clinical
      parameters returned to normal within several hours. The day after completion of
      fibrinolytic therapy, repeat contrast CT angiography showed total resolution of
      SVC thrombosis. Slow infusion of tPA may be effective in the treatment of SVC
      syndrome caused by acute thrombosis.

PMID- 19404036
TI  - Exercise-induced ventricular tachycardia associated with asymptomatic Brugada
      syndrome in a patient with urinary bladder stone.
AB  - It is well-known that autonomic nerve modulation has an important role in the
      occurrence of ventricular tachyarrhythmias in Brugada syndrome. A 59-year-old man
      underwent cardiac evaluation before surgery for urinary bladder stone. He had no
      cardiac complaints and the only coronary risk factor was heavy smoking. The
      electrocardiogram showed a saddleback type ST-segment elevation in leads V1-V2,
      and left axis deviation. During exercise stress test, ventricular tachycardia
      with a left bundle branch block pattern appeared, and the saddleback type ST
      segment elevation in V2 changed into a coved-type ECG at the recovery phase. The
      ventricular tachycardia was hemodynamically stable and normalized without
      medication. An echocardiogram showed normal left and right ventricular functions,
      and subsequent coronary angiography revealed normal coronary arteries. Based on
      these findings, a diagnosis of asymptomatic Brugada syndrome was made.
      Considering this particular case, it can be speculated that bladder-cardiac
      reflex may stimulate the autonomic nervous system via the vagus nerve and unmask
      Brugada syndrome.

PMID- 19404037
TI  - An important cause of dyspnea after coronary artery bypass grafting: phrenic
      nerve paralysis.
AB  - Diaphragmatic paralysis (DP) due to phrenic nerve paralysis is a rare
      complication after cardiac surgery. A 48-year-old male patient developed
      respiratory insufficiency, tachypnea, sinus tachycardia, chest pain, pneumonia,
      and fever immediately after coronary artery bypass grafting. Paradoxical movement
      of the epigastrium was noted during spontaneous ventilation and the chest X-ray
      showed elevation of the left hemidiaphragm. The diagnosis of DP was confirmed by
      ultrasonographic assessment. Antibiotherapy and intermittent positive airway
      pressure ventilation by a nasal mask resulted in significant improvement in the
      general condition of the patient. Respiratory problems were observed only on
      exertion. Spontaneous recovery of DP was considered and the patient was
      discharged 10 days after surgery with grade 1 dyspnea. However, after six months
      of follow-up, increased elevation of the left hemidiaphragm was noted on the
      chest X-ray with worsening respiratory discomfort even at rest. Thoracoscopic
      diaphragmatic plication was performed. After the operation, dyspnea disappeared,
      the chest X-ray showed the left hemidiaphragm in its normal position, and there
      was marked improvement in spirometric values.

PMID- 19404038
TI  - [Endomyocardial disease: a case report].
AB  - Endomyocardial disease is a form of restrictive cardiomyopathy, of unknown
      etiology, which occurs most commonly in tropical and subtropical areas. It is
      characterized by the formation of endomyocardial fibrosis of the apical and
      subvalvular regions of one or both ventricles. A 29-year-old male patient was
      admitted with restrictive cardiomyopathy and decompensated heart failure.
      Telecardiography showed cardiomegaly and right pleural effusion. Transthoracic
      echocardiography revealed preserved left ventricular systolic functions, biatrial
      dilatation, apical obliteration of both ventricles, increased endocardial
      echoreflectivity, and pericardial effusion. The right ventricular outflow tract
      was dilated. There was no endocardial thickening in this region. Doppler
      examination showed grade 3 mitral and tricuspid regurgitation. Ventriculograms
      showed apical obliteration of both ventricles, marked decrease in the size of the
      right ventricular cavity, significant dilatation of the right ventricular outflow
      tract and both atria, and severe mitral and tricuspid regurgitation. Laboratory
      findings showed no hypereosinophilia. Hepatic congestion, splenomegaly, and
      ascites were noted on abdominal ultrasonography. Following cardiac
      catheterization, the patient was placed on the waiting list for cardiac
      transplantation.

PMID- 19404039
TI  - [A case of aortic coarctation mimicking interrupted aorta].
AB  - An asymptomatic, healthy, 19-year-old male patient was examined for aortic
      coarctation upon detection of a heart murmur and hypertension on routine physical
      examination. Transthoracic echocardiography (TTE) showed rupture of the sinus of
      Valsalva and bicuspid aortic valve. Findings of aortography and computed
      tomography (CT) angiography were compatible with an interrupted aorta. For
      further delineation, transesophageal echocardiography (TEE) was performed and
      color Doppler imaging showed passage at the site of the descending aorta, which
      was suggestive of interruption by other imaging methods. The patient underwent
      surgery for aortic coarctation. At surgery, severe aortic coarctation was noted
      and corrected. Although TTE is usually adequate for the diagnosis of aortic
      coarctation, even aortography and CT angiography were misleading in this
      particular case, and differentiation from interrupted aorta was only possible by
      TEE.

PMID- 19404040
TI  - Case images: intrapericardial bullet.

PMID- 19404041
TI  - [Case images: Spontaneous coronary artery spasm during coronary angiography].

PMID- 19404042
TI  - [Case images: mitral valve mass: echocardiography and magnetic resonance imaging
      findings].

PMID- 19404043
TI  - [Letter to the editor: Turkey's publications in cardiovascular medicine].

PMID- 19404044
TI  - [Global risk and objectives in cardiovascular diseases].
AB  - The management of diseases arising from a single cause is straightforward.
      However, with regard to the clinical manifestations of atherosclerotic disease
      (coronary heart disease, stroke, peripheral vascular disease, and aneurysms) the
      situation is more complex, since atherosclerosis represents the product of
      multiple interacting risk factors. The modern approach to managing cardiovascular
      risks is to reduce an individual's total or global risk, rather than grading risk
      by individual risk factors alone. Recent guidelines stress the need for total
      risk estimation and recommend the use of risk charts like Framingham or SCORE
      before treating risk factors like dyslipidemia. One should keep in mind that
      treatment should be directed to those at greatest risk and management decisions
      based on a single risk factor may be misleading. For instance, a male smoker with
      a cholesterol level of 200 mg/dl and systolic blood pressure of 160 mmHg can be
      at four times higher risk than a female non-smoker with a cholesterol level of
      300 mg/dl and systolic blood pressure of 120 mmHg, indicating a higher global
      risk and priority for the treatment of dyslipidemia. If risk assessment is based
      on the cholesterol alone, then this woman would have a higher priority than the
      man due to the higher cholesterol level. In this review, global risk management
      strategies will be discussed in detail.

PMID- 19404045
TI  - [Dyslipidemia, atherosclerosis, and vulnerable plaques: the effect of
      atorvastatin on atherosclerosis and plaque structure].
AB  - Atherosclerotic vascular disease is characterized by inflammation and lipid
      accumulation resulting from detrimental effects of several risk factors on
      vascular structure, including dyslipidemia. The disease progresses slowly and
      insidiously resulting in acute coronary syndromes when the plaque ruptures. The
      plaques having a high propensity to rupture are defined as vulnerable. The
      vulnerability of the plaque is determined by several factors such as its lipid
      content, degree of inflammation, strength of the fibrous cap, degree of
      apoptosis, necrosis, and neovascularization. The patient's risk profile and
      characteristics are also related to the vulnerability of plaques. The main aim in
      preventive cardiology is to prevent the formation of atherosclerotic plaques or
      to stabilize the existing plaques to decrease cardiovascular events. Lifestyle
      modifications, reduction in risk factors, and some pharmacologic measures can
      improve plaque stabilization. Statins contribute to plaque stabilization by their
      lipid lowering and pleiotropic effects. Several studies have shown that, with
      statin treatment, the plaque becomes more stable, resulting in a decrease in
      cardiovascular events. This review summarizes the studies about plaque
      stabilizing effects of atorvastatin.

PMID- 19404046
TI  - [Atorvastatin in primary prevention].
AB  - Statins are one of the most widely used drugs in medical treatment and have been
      shown to prevent cardiovascular disease or reduce risk in a large number of
      studies. Although there is a general class effect, there are differences with
      regard to structure and efficacy between these agents. Among these agents,
      atorvastatin is a potent statin whose efficacy has been demonstrated in many
      clinical trials. Despite the presence of numerous clinical studies, data on
      atorvastatin related to primary prevention are limited compared to secondary
      prevention. In this article, clinical results of primary prevention trials with
      atorvastatin and data on its cost-effectiveness are reviewed. It is concluded
      that atorvastatin has a role in primary prevention and the cost of its use seems
      to be lower than commonly accepted cost-effectiveness thresholds.

PMID- 19404047
TI  - [Atorvastatin in secondary prevention].
AB  - During the 10 years of atorvastatin availability in the Turkish market, the
      physicians have had the opportunity to observe the accumulation of data related
      to its beneficial effect on clinical endpoints. The scope of this review is
      limited to the trials concerning the role of atorvastatin in secondary
      prevention. In GREACE and ALLIANCE studies, the benefit of atorvastatin was
      demonstrated in patients with coronary heart disease in real-world setting. TNT
      was the first trial which showed that aggressive lipid lowering therapy was more
      protective than a moderate one in patients with stable coronary artery disease.
      In the MIRACL trial, 80 mg atorvastatin was compared with placebo and found
      effective in preventing ischemic events in patients with non-ST elevation acute
      coronary syndromes. PROVE-IT proved that aggressive lipid lowering therapy with
      atorvastatin 80 mg was much more effective than moderate therapy (pravastatin 40
      mg) in patients with all types of acute coronary syndromes. AVERT was the first
      statin trial to show that aggressive therapy with atorvastatin was at least as
      effective as angioplasty in patients with stable coronary artery disease. The
      SPARCL trial demonstrated the efficacy of atorvastatin in secondary prevention of
      patients with stroke.

PMID- 19404048
TI  - [Statins with a perspective of lifelong therapy].
AB  - LDL cholesterol is the primary target of treatment for lowering the risk of
      cardiovascular events in both primary and secondary prevention. The usual drug to
      achieve this goal is HMG-CoA reductase inhibitors (statins), which constitute the
      most potent and effective class to reduce LDL cholesterol. Statins have been
      shown to be associated with good patient compliance, lower adverse events, and
      few drug interactions. Clinical trials have demonstrated that statin therapy
      reduces all clinical manifestations of atherosclerotic disease. These trials have
      also shown that the amount of risk reduction achieved is closely related to the
      degree of adherence to treatment. Despite evidence for the benefits of LDL
      lowering with statins, initiation of treatment, achievement of the goals, and
      long-term adherence to therapy remain far from optimal. However, in order to
      achieve maximum benefit from statin therapy as seen in clinical trials, it is
      important that patients receive optimal-dose therapy for the rest of their lives.
      This review is concerned with a combination of patient-, physician-, and health
      delivery system-focused interventions, as outlined by the ATP III guidelines to
      improve adherence in clinical practice.

PMID- 19404052
TI  - Lymph node harvest after proctectomy for invasive rectal adenocarcinoma following
      neoadjuvant therapy: does the same standard apply?
AB  - PURPOSE: Recent reports indicate that neoadjuvant therapy significantly reduces
      the lymph node harvest of rectal cancer. The aim of this study was to interpret
      the lymph node harvest in this setting based on the primary tumor response.
      METHODS: All patients undergoing proctectomy were included. Three variables were
      used as indicators of primary tumor response: ypT stage, tumor size, and tumor
      regression grade. RESULTS: From 1998 to 2007, 237 patients were identified: 157
      in the neoadjuvant therapy group and 80 in the nonneoadjuvant therapy group.
      Neoadjuvant therapy significantly reduced the number of lymph nodes harvested (P
      = 0.011). Compared with the nonneoadjuvant group, there were significantly fewer
      lymph nodes in the neoadjuvant early T stage group (P = 0.001), small tumor size
      group (P = 0.003), and low tumor regression grade group (P < 0.001). However,
      there was no significant difference between the nonneoadjuvant group and the
      neoadjuvant advanced T stage (P = 0.664), large tumor (P = 0.815), and high tumor
      regression grade groups (P = 0.566). CONCLUSION: The current standard of lymph
      node harvest should be applied to patients with poorly responding primary tumors
      after neoadjuvant therapy. However, a new standard may be necessary to define the
      adequate number of lymph nodes for tumors that respond well to neoadjuvant
      therapy.

PMID- 19404053
TI  - Long-term morbidity and oncologic outcomes of laparoscopic-assisted anterior
      resection for upper rectal cancer: ten-year results of a prospective, randomized
      trial.
AB  - PURPOSE: We have previously reported the five-year results of a randomized trial
      comparing laparoscopic and open resection for cancer of the upper rectum and
      rectosigmoid junction. The aim of this follow-up study is to report on the long
      term morbidity and ten-year oncologic outcomes among the subgroup of patients
      with upper rectal cancer. METHODS: From September 1993 to October 2002, 153
      patients with upper rectal cancer were randomly assigned to receive either
      laparoscopic-assisted (n = 76) or open (n = 77) anterior resection. Patients were
      last followed up in December 2007. Long-term morbidity, survival, and disease
      free interval were prospectively recorded. Data were analyzed by intention-to
      treat principle. RESULTS: The demographic data of the two groups were comparable.
      More patients in the open group developed adhesion-related bowel obstruction
      requiring hospitalization (P = 0.001) and intervention. The overall long-term
      morbidity rate was also significantly higher in the open group (P = 0.012). After
      curative resection, the probabilities of cancer-specific survival at ten years of
      the laparoscopic-assisted and open groups were 83.5 percent and 78.0 percent,
      respectively (P = 0.595), and their probabilities of being disease-free at ten
      years were 82.9 percent and 80.4 percent, respectively (P = 0.698). CONCLUSION:
      Laparoscopic-assisted anterior resection for upper rectal cancer is associated
      with fewer long-term complications and similar ten-year oncologic outcomes when
      compared with open surgery.

PMID- 19404054
TI  - Outcomes of surgery alone for lower rectal cancer with and without pelvic
      sidewall dissection.
AB  - PURPOSE: The goal of this retrospective multicenter study was to investigate the
      efficacy of pelvic sidewall dissection for lower rectal cancer. METHODS: Data
      from 1,272 consecutive patients who underwent total mesorectal excision for lower
      rectal cancer in 12 institutions from 1991 through 1998 were reviewed. The rates
      of local recurrence and survival in patients with pelvic sidewall dissection were
      compared with those without pelvic sidewall dissection. Logistic regression
      analysis was used to determine independent risk factors for lymph node metastasis
      and local recurrence, and the Cox proportional hazards model was used to
      determine independent prognostic factors. RESULTS: Of the 1,272 patients, 784
      underwent pelvic sidewall dissection. Among them, 117 patients (14.9 percent) had
      lateral pelvic lymph node metastasis. Risk factors for lateral pelvic lymph node
      metastasis included female gender, tumor not well-differentiated adenocarcinoma,
      and perirectal lymph node metastasis. Lateral pelvic and perirectal lymph node
      metastases were independent risk factors for local recurrence. The Cox
      proportional hazard model showed age, grade of histology, invasion depth of the
      tumor, perirectal lymph node metastasis, and lateral pelvic lymph node metastasis
      to be independent prognostic factors. No significant differences between patients
      with and those without pelvic sidewall dissection were seen regarding rates of
      local recurrence (10.5 percent vs. 7.4 percent) or five-year overall survival
      (75.8 percent vs. 79.5 percent). Although the proportion of patients with
      advanced stages of disease was greater in patients who had pelvic sidewall
      dissection, no differences between the two groups were seen in local recurrence
      even when tumor category was taken into account. However, lack of pelvic sidewall
      dissection was a predictor of poor prognosis. CONCLUSIONS: Although pelvic
      sidewall dissection does not appear to confer overall benefits regarding local
      recurrence or survival, the effectiveness of pelvic sidewall dissection in
      specific patient groups remains uncertain. A randomized controlled study is
      necessary to clarify this issue.

PMID- 19404055
TI  - Long-term survival after transanal excision of T1 rectal cancer.
AB  - PURPOSE: Several series report higher recurrence after transanal excision of T1
      rectal cancer than after radical resection. However, the impact of transanal
      excision on cancer mortality has not been adequately studied. The purpose of this
      study was to compare oncologic outcomes of transanal excision with those of
      radical resection. METHODS: Patients with transanal excision or radical resection
      for T1 rectal cancer treated between 1985 and 2004 were identified from a
      prospective database. Patients receiving preoperative chemotherapy or radiation
      or with tumors >12 cm from the anal verge were excluded. RESULTS: The final
      cohort comprised 145 radical resections and 137 transanal excisions. The
      transanal excision group was notable for older mean age (64 vs. 59 years),
      shorter mean distance from anal verge (5.9 vs. 7.8 cm), and smaller tumor size
      (2.3 vs. 3.1 cm). Lymphovascular invasion and poor differentiation were similar
      in both groups. Twenty percent of radical resection specimens had lymph node
      metastasis. Median follow-up was 5.6 years. Local recurrence was noted in a
      higher proportion of transanal excision patients (13.2 vs. 2.7 percent, P =
      0.001). After transanal excision the hazard ratio for local recurrence was 11.3
      (95 percent confidence interval, 2.6-49.2), and disease-specific survival was
      inferior (87 vs. 96 percent at 5 years, P = 0.03, hazard ratio 2.8 [range, 1.04
      7.3]). CONCLUSIONS: Transanal excision offers inferior oncologic results,
      including greater risk of cancer-related death. This procedure should be
      restricted to patients who have prohibitive medical contraindications to major
      surgery or have made an informed decision to accept the oncologic risks of local
      excision and avoid the functional consequences of rectal resection.

PMID- 19404056
TI  - Impact of the aging population on the demand for colorectal procedures.
AB  - PURPOSE: With the baby boomers entering retirement age, the United States
      population is seeing a dramatic increase in the number of elderly individuals. We
      hypothesized that as a result, during the next 20 years, the demand for
      colorectal procedures will grow rapidly. METHODS: We used the 2005 Nationwide
      Inpatient Sample and the Florida State Ambulatory Surgery Database as source
      data. From these two data sources, we identified commonly performed inpatient and
      outpatient colorectal procedures, as well as associated diagnoses. These data
      were combined with census projections to generate projected volumes for the
      selected procedures and diagnoses. RESULTS: Between 2005 and 2025, the United
      States population is expected to grow by 18 percent, with disproportionate growth
      in individuals aged 65 to 74 years (92 percent) and those aged 75+ years (54
      percent). We forecast that growth in outpatient procedures and inpatient
      procedures will be 21.3 percent and 40.6 percent, respectively. Inpatient
      operations for colon cancer and rectal cancer show the greatest growth.
      CONCLUSIONS: During the next two decades, demographic changes in the United
      States population will lead to a marked increase in the use of colorectal
      surgical services, especially inpatient and oncologic procedures. The ability of
      the surgical workforce to meet this projected growth in demand should be
      assessed.

PMID- 19404059
TI  - Stapled transanal rectal resection vs. transvaginal rectocele repair for
      treatment of obstructive defecation syndrome.
AB  - PURPOSE: Stapled transanal rectal resection has been introduced as a new
      technology for the management of obstructive defecation syndrome. In this study
      we observed the clinical outcomes for stapled transanal rectal resection as
      compared with transvaginal rectocele repair for obstructive defecation syndrome.
      METHODS: This study is a retrospective review of patients who received
      transvaginal rectocele repair for obstructive defecation syndrome from June 1997
      to February 2002 as compared with patients who received stapled transanal rectal
      resection from June 2005 to August 2007. The clinical outcomes observed were
      operative time, estimated blood loss, length of stay, complication rate,
      procedure failure rate, recurrence rate, time to recurrence, and dyspareunia
      rate. RESULTS: Thirty-seven patients had transvaginal rectocele repair for
      management of obstructive defecation syndrome, and 36 patients had stapled
      transanal rectal resection. There was no difference in the age of patients
      receiving either procedure (transvaginal rectocele repair, 57.92 years old;
      stapled transanal rectal resection, 53.19 years old; P = 0.1096). Evaluation of
      the clinical outcomes showed that transvaginal rectocele repair had a longer
      operative time (transvaginal rectocele repair, 85 minutes; stapled transanal
      rectal resection, 52 minutes; P = or<0.0001), greater estimated blood loss
      (transvaginal rectocele repair, 108 ml; stapled transanal rectal resection, 43
      ml; P = 0.0015), and a lower complication rate (transvaginal rectocele repair,
      18.9 percent; stapled transanal rectal resection, 61.1 percent; P = 0.0001).
      CONCLUSION: The stapled transanal rectal resection procedure can be done with
      shorter operative times and less blood loss than transvaginal rectocele repair,
      however, it has a higher complication rate.

PMID- 19404060
TI  - Brush cytology for the diagnosis of colorectal cancer.
AB  - PURPOSE: The purpose of this study was to analyze the results of brush cytology
      for the diagnosis of colorectal cancer and compare them with the results of
      endoscopic biopsy and histologic evaluation of the resected specimen. METHODS:
      Nine hundred eighteen patients who had brush cytology, endoscopic biopsy, and a
      definitive resection of a colorectal lesion between 1990 to 2006 were identified
      from our pathology database. RESULTS: Cytology alone had a sensitivity of 88.2
      percent, a specificity of 94.1 percent, a positive predictive value of 98.6
      percent, and a negative predictive value of 61.9 percent for the diagnosis of
      colorectal cancer. Brush cytology always recognized malignant cells, with a
      positive predictive value of 100 percent. There was no significant difference
      between brush cytology and biopsy, which had a sensitivity of 86.9 percent,
      specificity of 98.1 percent, positive predictive value of 99.5 percent, and a
      negative predictive value of 60.3 percent. Combining the results of brush
      cytology and biopsy resulted in a statistically significant increase in
      sensitivity to 97.4 percent (P < 0.001), a significant increase in the negative
      predictive value to 88.4 percent (P < 0.001), and a significant reduction in the
      false-negative rate to 0.03 percent (P < 0.001) for the diagnosis of colorectal
      cancer. CONCLUSIONS: Brush cytology is as accurate as endoscopic biopsy for the
      diagnosis of colorectal cancer, and combining these two diagnostic modalities
      resulted in a significant improvement in the definitive diagnosis of cancer,
      which might reduce the need for further biopsy.

PMID- 19404061
TI  - An experimentally successful new sphincter-conserving treatment for anal fistula.
AB  - PURPOSE: A new sphincter-conserving treatment was evaluated in a porcine model.
      METHODS: A total of 36 fistulas were created by procedures that have been
      published previously. At fistula induction a skin biopsy was taken from which to
      culture fibroblasts. Four weeks after induction, when fistulas were well
      established, the fistula tracks were cored out. Collagen paste modified from
      Permacol injection (Covidien, Mansfield, MA) was then used as a solitary infill
      material in 11 tracks, cultured autologous fibroblasts being added to this in a
      further 18 tracks. The track was cored out in seven controls, but these tracks
      were not treated with infill material. All of the internal and external openings
      were closed. Anorectal excision was then carried out under terminal anesthesia at
      2 to 12 weeks. Histologic examination of individual tracks was performed by an
      experienced pathologist. RESULTS: In this quadruped all of the infilled tracks
      healed, autologous fibroblasts having the best tissue integration, but only two
      of seven control tracks healed. CONCLUSIONS: Removal of the fistula track
      followed by injection of collagen healed all of the cases. The addition of
      autologous fibroblasts improved the histologic appearance of the tracks. A pilot
      study in human fistula patients is in progress.

PMID- 19404062
TI  - Laparoscopic peritoneal lavage or primary anastomosis with defunctioning stoma
      for Hinchey 3 complicated diverticulitis: results of a comparative study.
AB  - PURPOSE: This study was designed to compare postoperative outcomes of
      laparoscopic peritoneal lavage and open primary anastomosis with defunctioning
      stoma in the management of Hinchey 3 diverticulitis. METHODS: From 1994 to 2006,
      35 patients underwent laparoscopic peritoneal lavage for Hinchey 3 diverticulitis
      in three institutions. Data prospectively collected were compared with those of a
      retrospective series of 24 patients matched for Hinchey's classification and who
      underwent primary anastomosis with defunctioning stoma. RESULTS: There was no
      postoperative death. Postoperative morbidity was not different between the two
      groups. One patient in the laparoscopic peritoneal lavage group required a
      Hartmann's procedure because of a colonic fistula. One patient in the primary
      anastomosis with defunctioning stoma group underwent a reoperation for incisional
      dehiscence. The median hospital stay was lower in patients treated by
      laparoscopic peritoneal lavage (8 vs. 17 days, P < 0.0001). Twenty-five patients
      in the laparoscopic peritoneal lavage group underwent elective laparoscopic
      resection. One of them required conversion to laparotomy. All patients in the
      primary anastomosis with defunctioning stoma group have had their ileostomy
      closed. Cumulative surgical morbidity (16 vs. 37.5 percent, P = 0.0507) and
      hospital stay (14 vs. 23 days, P < 0.0001) were lower in the laparoscopic
      peritoneal lavage group. CONCLUSION: In the management of Hinchey 3
      diverticulitis, laparoscopic peritoneal lavage does not result in excess
      morbidity or mortality, it reduces the length of hospital stay and avoids a stoma
      in most patients, and it is, therefore, a reasonable alternative to primary
      anastomosis with defunctioning stoma.

PMID- 19404063
TI  - Evidence-based and clinical outcome scores to facilitate audit and feedback for
      colorectal cancer care.
AB  - PURPOSE: To describe a methodology for surgical audit and feedback based on
      hospital-level indicators of the quality of colorectal cancer care. METHODS:
      Process and outcome indicators were identified from a population-based database
      (N = 3095 patients treated by 258 surgeons at 130 hospitals across New South
      Wales between February 1, 2000 and January 31, 2001). Hospitals were ranked on
      each indicator, with those in the lowest 20th percentile receiving a score of 0
      and the remainder receiving a score of 1. Scores for individual indicators were
      then summed for each hospital and divided by the number of relevant indicators to
      provide an evidence-based score (EBS) and a clinical outcome score. RESULTS: Ten
      process and six clinical outcome indicators were identified. Hospital-level
      summary scores ranged from 0.14 to 1.0 for evidence-based processes and from 0.17
      to 1.0 for clinical outcomes. Evidence-based score and clinical outcome score
      were independent (r = 0.12, P = 0.32). There was a small positive association
      between evidence-based score and caseload (r = 0.33, P = 0.005) but clinical
      outcome score and caseload were unrelated (r = 0.11, P = 0.36). CONCLUSIONS:
      Evidence-based score and clinical outcome score address different aspects of
      quality of care. The wide variability of hospitals' outcome scores and an
      association of evidence-based score and caseload indicate that simple scores may
      be useful in audit and feedback.

PMID- 19404066
TI  - Outcomes and prognostic factors for squamous-cell carcinoma of the anal canal:
      analysis of patients from the National Cancer Data Base.
AB  - PURPOSE: The objective of this study was to assess survival and prognostic
      factors for anal carcinoma in the population. METHODS: Patients with squamous
      cell carcinoma of the anal canal were identified from the National Cancer Data
      Base (1985-2000). Univariate and multivariable methods were used to assess
      factors associated with survival. Concordance was calculated to assess agreement
      between American Joint Committee on Cancer stage and actual outcome. RESULTS:
      Nineteen thousand one hundred ninety-nine patients with anal carcinoma were
      identified (Stage I, 25.3 percent; Stage II, 51.8 percent; Stage III, 17.1
      percent; Stage IV, 5.7 percent). Overall five-year survival was 58.0 percent. The
      American Joint Committee on Cancer (6th edition) staging system provided good
      survival discrimination by stage: I, 69.5 percent; II, 59.0 percent; III, 40.6
      percent; and IV, 18.7 percent (concordance index, 0.663). On multivariable
      analysis, patients with anal carcinoma had a higher risk of death if they were
      male, >or=65 years old, black, living in lower median incomes areas, and had more
      advanced T stage tumors, nodal or distant metastases, or poorly differentiated
      cancers (P < 0.0001). There was not a significant difference in survival by
      hospital type or year of diagnosis. CONCLUSION: Although tumor characteristics
      and staging affect prognosis, patient factors, such as gender, race, and
      socioeconomic status, are also important prognostic factors for squamous-cell
      carcinoma of the anal canal.

PMID- 19404067
TI  - Magnetic resonance imaging prediction of an involved surgical resection margin in
      low rectal cancer.
AB  - PURPOSE: Low rectal cancers (<5 cm from the anal verge), compared with all
      others, have greater positive resection margin rates, attributed to mesorectal
      tapering and higher perforation risk. The aim of this study was to assess
      positive resection margin prediction by using magnetic resonance imaging staging.
      METHODS: The following features were analyzed by using preoperative magnetic
      resonance imaging from 101 consecutive patients with low rectal tumors: tumor
      location (posterior/anterior) and magnetic resonance stage (Stage 1-2, tumor
      within the intersphincteric plane; Stage 3-4 tumor extending into the
      intersphincteric plane). Magnetic resonance imaging tumor regression grade was
      measured where posttreatment magnetic resonance imaging was available and
      compared with histopathologic findings. RESULTS: Seventy of 101 patients had
      abdominoperineal excisions, and 31 of 101 had low anterior resections. Using
      logistic regression, positive resection margin odds were higher for magnetic
      resonance Stages 3 to 4 than Stages 1 to 2 by a factor of 17.7 (P < 0.001), and
      positive resection margin odds were higher by a factor of 2.8 for anterior vs.
      posterior tumors (P = 0.026). Magnetic resonance imaging tumor regression grade
      strongly predicted for positive resection margins; 11 of 15 patients with little
      treatment response had positive resection margins, compared with 2 of 15 with >50
      percent complete treatment response on magnetic resonance imaging (P < 0.001).
      CONCLUSION: Significant magnetic resonance imaging positive resection margin
      predictors are tumor into or beyond the intersphincteric plane and magnetic
      resonance imaging tumor regression grade.

PMID- 19404068
TI  - Hand-assisted laparoscopic vs. open subtotal colectomy for severe ulcerative
      colitis.
AB  - PURPOSE: This study aimed to assess the feasibility and safety of undergoing
      emergency subtotal colectomy with hand-assisted laparoscopic surgery in patients
      with severe ulcerative colitis. METHODS: We reviewed the medical records of 60
      patients who underwent emergency subtotal colectomy with hand-assisted
      laparoscopic technique (30 cases) or open technique (30 cases) for severe
      ulcerative colitis. RESULTS: No intraoperative complications occurred in either
      group. One patient in the laparoscopic group required conversion to open surgery.
      The median operative time was significantly longer in the laparoscopic group (242
      vs. 191 minutes; P < 0.001). The rate of early postoperative complications in the
      laparoscopic group was significantly less than that in the open group (37 percent
      vs. 63 percent; P = 0.041). In the open group, four patients required
      relaparotomy because of peritoneal abscess or strangulation ileus, whereas no
      patient required relaparotomy in the laparoscopic group (P = 0.040). In the
      laparoscopic group, the median duration of postoperative food prohibition was
      significantly shorter (4.8 vs. 5.9 days; P = 0.007), and the median length of
      hospital stay was significantly shorter (23.0 vs. 33.0 days; P = 0.001).
      CONCLUSIONS: Although the operative time was elongated in the laparoscopic group,
      intraoperative safety and postoperative recovery were satisfactory. For severe
      ulcerative colitis, hand-assisted laparoscopic surgery can be an alternative to
      conventional open surgery.

PMID- 19404069
TI  - Perineal Crohn's disease: an indicator of poor prognosis and potential
      proctectomy.
AB  - PURPOSE: There is a subset of patients with perianal Crohn's disease whose course
      is unusually severe. The hypotheses of this study are that these patients often
      have direct perineal involvement with Crohn's disease and that this involvement
      can be recognized clinically. METHODS: A prospective database with data from 1989
      to 2005 was examined for patients with perianal Crohn's disease. Patients were
      divided into those with and those without perineal involvement, defined by the
      presence of at least one of the following findings: spontaneous perineal
      ulceration; nonhealing, painless fissures; or waxy perineal edema. Presentation,
      treatment, and outcome of the two groups were compared. RESULTS: Seventy-two
      patients were identified, 19 with perineal involvement and 63 without. Perineal
      Crohn's disease was more often seen in women, presented at a younger age, and was
      associated with less small bowel and more colonic Crohn's. The chances of healing
      in patients with perineal Crohn's disease were lower (32 vs. 66 percent) and
      proctectomy was more likely (26 vs. 3.7 percent) than when the perineum was
      normal. CONCLUSION: Perineal involvement with Crohn's disease can be diagnosed on
      physical examination and confirmed by the finding of granulomas. When perineal
      involvement is suspected, surgery should be avoided and consideration given to
      medical therapy.

PMID- 19404070
TI  - Laparoscopic intracorporeal ileocolic resection for Crohn's disease: is it safe?
AB  - PURPOSE: The aim of this study was to assess the impact of laparoscopic ileocolic
      resection with intracorporeal vascular division and anastomosis on the outcome of
      patients with terminal ileal Crohn's disease. METHODS: Prospective data on
      patients undergoing laparoscopic ileocolic resection for Crohn's disease confined
      to terminal ileum and cecum with or without fistulas were reviewed. Exclusion
      criteria were frozen abdomen, recurrent Crohn's disease following resection, and
      perforated Crohn's disease. Laparoscopic ileocolic resection involved a lateral
      to-medial approach encompassing ten sequential steps. Values were medians
      (range). RESULTS: From January 1992 to June 2006, 80 laparoscopic ileocolic
      resections were attempted with a 1.2 percent conversion rate. Sixty-two women and
      18 men, age 40 (19-55) years, had a body mass index of 26 (18-37) and an American
      Society of Anesthesiologists' score of 1 (1-3), and 23.7 percent had previously
      undergone abdominal surgery. Operating time was 155 (130-210) minutes. Estimated
      blood loss was 250 (50-600) ml. Length of the skin incision at the specimen
      extraction site was 35 (30-44) mm. The complication/reoperation rate was 7.5
      percent. The readmission rate was 3.7 percent. Except for smoking (P < 0.005),
      there were no significant differences between patients with and those without
      complications. The recurrence rate was 30 percent (24 of 80). The median time to
      recurrence was 64 months. CONCLUSION: Laparoscopic ileocolic resection with
      intracorporeal vascular division and anastomosis resulted in a favorable outcome
      in selected patients with refractory terminal ileal Crohn's disease.

PMID- 19404071
TI  - Electrothermal bipolar vessel sealing system vs. harmonic scalpel in colorectal
      laparoscopic surgery: a prospective, randomized study.
AB  - PURPOSE: This study was designed to compare the efficacy and safety of
      laparoscopic colorectal surgery performed with the aid of LigaSure vessel-sealing
      system or Ultracision. METHODS: Patients eligible for elective laparoscopic right
      or left hemicolectomy or anterior resection of rectum were randomly assigned to
      either the use of Ligasure or Ultracision. The primary end point was
      intraoperative reduction of blood loss. Secondary end points were intraoperative
      and postoperative morbidity and operative time. RESULTS: Between April 2005 and
      December 2006, 140 consecutive patients were included in the study (70 Ligasure
      and 70 Ultracision. We performed 31 right hemicolectomies, 69 left
      hemicolectomies, and 40 anterior resections of rectum. Blood loss was 109.6 ml
      (Ultracision 107.9 ml vs. Ligasure 111.2 ml, P value = 0.72). Intraoperative
      complication rate was 2.8 percent (Ultracision 1.4 percent vs. Ligasure 4.2
      percent, P value < 0.01). Postoperative mortality was 0.7 percent. The overall
      conversion rate was 7.8 percent, 6 in the Ligasure group and 5 in the Ultracision
      group (P value = 0.09). Operative time, considered from pneumoperitoneum to
      minilaparotomy, was 115.7 minutes (Ultracision 114.8 minutes vs. Ligasure 116.3
      minutes, P value = 0.89). CONCLUSIONS: Results showed that Ligasure and
      Ultracision are both useful instruments for laparoscopic colorectal surgery with
      no significant difference in terms of intraoperative/postoperative morbidity and
      operative time. Choice of which technique to perform should be according to the
      surgeon's preference.

PMID- 19404072
TI  - Personality rather than clinical variables determines quality of life after major
      colorectal surgery.
AB  - PURPOSE: Clinical factors, especially the presence of a stoma, have been presumed
      to be the major determinants of quality of life after colorectal surgery. We
      investigated the relative influence of other variables, e.g., patient's
      personality, sense of coherence, and coping strategies, to determine the validity
      of this long-held assumption. METHODS: We investigated 79 patients undergoing
      major colorectal surgery. Quality of Life was assessed with the Short Form-36 and
      Gastrointestinal Quality of Life Index questionnaires at three and 12 months
      postsurgery. Additionally, baseline psychologic data on personality and sense of
      coherence were assessed. The results were analyzed in both a bivariate manner and
      by multivariate hierarchical regression analysis. RESULTS: In the bivariate
      analysis, clinical parameters had a small and temporary effect on quality of
      life, if any. In the multivariate model the character of the underlying disease
      and the presence of a stoma did not affect quality of life significantly. In
      contrast, emotional lability, extraversion, and sense of coherence had a strong
      and lasting influence, accounting for 49 percent of variance (Delta R2) for
      emotional quality of life, 22 percent for physical and 32 percent for disease
      specific Quality of Life. CONCLUSION: Personality exerts a strong and lasting
      effect on quality of life after colorectal surgery. This effect by far exceeds
      the influence of common clinical variables.

PMID- 19404073
TI  - Longitudinal assessment of quality of life in rectal cancer patients with or
      without stomas following primary resection.
AB  - PURPOSE: The purpose of this study was to assess the longitudinal impact of stoma
      formation on the health-related quality of life of rectal cancer patients treated
      with adjuvant chemotherapy. METHODS: Health-related quality of life data was
      prospectively collected in a randomized trial designed to compare 24 weeks of
      bolus 5-fluorouracil/leucovorin with 12 weeks of continuous 5-fluorouracil in
      patients with resected Dukes B and C colorectal cancer. Health-related quality of
      life data was collected at baseline, during adjuvant treatment, and at one and
      three years after completion of chemotherapy. RESULTS: Between 1993 and 2003, 186
      rectal cancer patients were enrolled. One hundred thirty-nine patients had
      anterior resection, of whom 46 had a temporary defunctioning colostomy. Forty
      seven patients had abdominoperineal resection with formation of a permanent
      colostomy. There was no significant difference in global health-related quality
      of life between patients with and patients without a stoma at any time point.
      However, during adjuvant treatment, role (P = 0.04) and social (P = 0.005)
      functioning were significantly worse in stoma patients than in nonstoma patients.
      Moreover, the impairment in social functioning persisted at one (P = 0.03) and
      three years (P = 0.04) after adjuvant chemotherapy. CONCLUSION: Our results
      demonstrate important adverse effects of either temporary or permanent stoma
      formation on subsequent health-related quality of life in patients with rectal
      cancer.

PMID- 19404075
TI  - Prognostic heterogeneity of endosonographic T3 rectal cancer.
AB  - PURPOSE: This study aimed to assess the prognostic implications of uT3 rectal
      carcinomas according to the tumor thickness and to analyze the correlation
      between this ultrasound-based parameter and other prognostic factors. METHODS:
      Seventy-four patients with uT3(pM0) rectal tumors underwent primary surgery from
      1996 to 2003. Preoperative endorectal ultrasound was used to assess uN stage,
      maximum tumor perimeter, and maximum tumor thickness. An ultrasound maximum tumor
      thickness cutoff point for local recurrence subdividing T3 tumors into uT3a and
      uT3b was established. RESULTS: Median follow-up was 41 months (range, 24-59). The
      5-year actuarial local and overall recurrence rates were 9.82 percent (n = 7) and
      42.46 percent (n = 23), respectively. uN stage(P = 0.05), circumferential
      resection margin involvement (P = 0.002), an ultrasound maximum tumor thickness
      (P = 0.01), and locally advanced tumors (P = 0.001) were related to a
      significantly increased risk of local recurrence. An ultrasound maximum tumor
      thickness (hazard ratio, 1.15; 95 percent confidence interval, 1.0-1.2) and
      locally advanced tumor (hazard ratio, 17.21; 95 percent confidence interval, 2.99
      98.84) were preoperative independent variables for predicting local recurrence.
      Locally advanced tumor was the only preoperative independent prognostic factor
      for overall recurrence (P = 0.004; hazard ratio, 1.09; 95 percent confidence
      interval, 1.0-1.1). An ultrasound maximum tumor thickness with a 19-mm cutoff
      point, subdividing the T3 tumors into uT3a and uT3b, can be used to predict local
      recurrence. Locally advanced tumors (P = 0.02) and circumferential resection
      margin involvement (P = 0.005) showed a significant association with an
      ultrasound maximum tumor thickness >19 mm. CONCLUSIONS: A maximum tumor thickness
      measured by endorectal ultrasound in pT3 rectal cancer is an independent
      prognostic factor for local and overall recurrence. An ultrasound maximum tumor
      thickness cutoff point of 19 mm may be useful to classify patients preoperatively
      and to select them for primary surgery or neoadjuvant therapy.

PMID- 19404074
TI  - Emergency first presentation of colorectal cancer predicts significantly poorer
      outcomes: a review of 356 consecutive Irish patients.
AB  - PURPOSE: Colorectal cancer commonly presents first as an emergency and is likely
      to be complicated by bowel obstruction/perforation requiring more difficult
      procedures, with poorer outcomes. Analysis of all of the procedures performed on
      patients diagnosed in Wexford General Hospital, Ireland, during the period 2000
      to 2006 was carried out to validate this hypothesis in our western European
      population. METHODS: Retrospective analysis of a prospectively maintained
      database of patient demographics, diagnosis, procedures, and mode of presentation
      (elective, emergency) was undertaken. RESULTS: A total of 356 patients with
      colorectal cancer underwent 498 procedures during the years 2000 to 2006. Eighty
      four emergency endoscopies and 100 emergency bowel resections were performed.
      Obstructive lesions were more likely to require emergency resection (P < 0.001).
      Median survival time for patients treated electively was 82 months vs. 59 months
      for patients treated on an emergency basis. CONCLUSIONS: Of all colonic
      resections, 34 percent were carried out as emergencies and were significantly
      more likely to be complicated by obstruction or perforation (P < 0.001).
      Emergency resections were associated with a significantly poorer perioperative
      mortality and five-year survival rate (P < 0.001). Forty-one percent of
      colorectal cancers diagnosed at endoscopy were first seen emergently. These data
      raise concerns regarding public awareness of colorectal cancer and resource
      allocation and reemphasize the need for a national colorectal screening program.

PMID- 19404076
TI  - Treatment of transsphincteric anal fistulas: are fistula plugs an acceptable
      alternative?
AB  - PURPOSE: Treatments for transsphincteric, cryptoglandular anal fistulas pose
      risks for high recurrence rates and impaired anal continence. Anal fistula plugs
      have gained popularity because of reports of success without compromising the
      anal sphincter. To examine the benefit of the anal fistula plug, we compared its
      success rate with a standard treatment for transsphincteric fistulas with similar
      indications, the transanal mucosal advancement flap. METHODS: We examined the
      outcomes of all patients with transsphincteric fistulas who underwent anal
      fistula plug repair from July 2005 to December 2006, excluding those with Crohn's
      disease or less than three months of follow-up. They were compared with a
      historical control group of patients (2001-2005) with similar transsphincteric
      fistulas who underwent a transanal mucosal advancement flap procedure because the
      anal fistula plug was not available. The same surgeons performed both procedures.
      Outcome was assessed from medical records or telephone follow-up. RESULTS: Twenty
      nine patients underwent an anal fistula plug repair, and 26 patients underwent a
      flap procedure. Fistula closure rates were 34 percent for plugs and 62 percent
      for flaps (P = 0.045). The groups were similar in all respects except that 3
      percent of plug patients and 58 percent of flap patients had postoperative
      inpatient stays and the median follow-up was longer (279 vs. 819 days) for the
      flap group. CONCLUSION: Fistula closure rates were significantly lower with anal
      fistula plugs than with advancement flaps. Although the low success rates for
      fistula plugs could be a result of patient selection, more data needs to be
      accrued before fistula plugs can be recommended as definitive first-line
      treatment for transsphincteric fistulas.

PMID- 19404077
TI  - Long-term outcome of Altemeier's procedure for rectal prolapse.
AB  - INTRODUCTION: Altemeier's procedure is infrequently applied in European countries
      and because of the small number of patients treated in each center, its long-term
      reliability is uncertain. METHODS: Medical records of 93 patients (median age, 77
      years) undergoing perineal rectosigmoidectomy associated with levatorplasty in 72
      patients (78 percent) were reviewed; 65 patients (70 percent) suffered from major
      fecal incontinence. RESULTS: There was no postoperative mortality. Eight (8.6
      percent) major complications were observed (3 pelvic hematomas, 1 anastomotic
      dehiscence, 1 sigmoid perforation, 1 pararectal abscess, and 2 late anal
      strictures), and 13 (14 percent) minor complications. At a mean follow-up of 41
      (range, 12-112) months the complete recurrence rate was 18 percent (17 patients);
      these patients were treated with a repeat Altemeier's procedure (6 patients),
      Delorme's operation (1 patient), Wells' rectopexy (1 patient), postanal repair (1
      patient), anal bulking agents (2 patients), and sacral nerve stimulation (2
      patients). Anal manometry significantly improved postoperatively. Incontinence
      improved postoperatively in 30 cases (28 percent), deteriorated in 2 patients,
      while 4 patients developed minor incontinence. CONCLUSIONS: Perineal
      rectosigmoidectomy for rectal prolapse is a relatively safe and effective
      treatment, in particular, for frail, older patients, with a low postoperative
      morbidity, but the recurrence rate is not negligible and restoration of
      continence is unpredictable.

PMID- 19404078
TI  - Measure of the voluntary contraction of the puborectal sling as a predictor of
      successful sphincter repair in the treatment of anal incontinence.
AB  - PURPOSE: Overlapping sphincteroplasty is the surgery of choice for incontinent
      patients with an anterior defect after childbirth. Numerous predictive factors
      have been proposed, but no preoperative variables have been successfully shown to
      be reproducible. The purpose of this study was to assess the prognostic value of
      voluntary contraction of the puborectal sling before sphincter repair for anal
      incontinence. METHODS: This prospective study evaluated 109 consecutive women who
      underwent surgery for postobstetric anal incontinence. Voluntary contraction of
      the puborectal sling was measured by perineal ultrasound before the surgery.
      Severity of anal incontinence was evaluated preoperatively and postoperatively
      with the Miller Incontinence Score (total incontinence = 18, complete continence
      = 0). RESULTS: The proportion of patients with scores <or=3 was 16.7 percent when
      the preoperative voluntary contraction of the puborectal sling was <or=4 mm, 48.1
      percent when it was 4.1 to 8 mm, and 98.7 percent when it was >8 mm (P < 0.001).
      Using <or=8 mm to define abnormal shortening, the sensitivity of the test was
      0.95 (95 percent confidence interval, 0.75-1.00) and specificity was 0.84 (95
      percent confidence interval, 0.75-0.91). CONCLUSION: A preoperative voluntary
      contraction of the puborectal sling >8 mm convincingly discriminates between
      patients with a good functional outcome and those with an unsatisfactory outcome
      after sphincter repair for postobstetric anal incontinence.

PMID- 19404079
TI  - Endosonography of the anal canal: findings in children.
AB  - PURPOSE: The aim of this study was to determine the endosonographic anatomy in
      children to define normal age-related differences in sphincter morphology and
      measurements. METHODS: One hundred ten consecutive children (76 males and 34
      females; mean age, 3.94 years; range, 1.10-15.09) with endoanal ultrasonography
      were studied. The thickness of the anal canal of the internal and external anal
      sphincter of each child was registered and correlated with the age. RESULTS: At
      the high level, the puborectalis muscles were clearly visualized, with a median
      thickness of 4.73 mm, and the internal anal sphincters were observed, with a mean
      thickness of 1.21 mm. At the mid level, both the internal and external anal
      sphincters were visualized, as well. The mean internal anal sphincter thickness
      was 1.23 mm and the median thickness of the external anal sphincter was 4.47 mm.
      At the lower level, the median external anal sphincter thickness was 5.39 mm.
      There was no significant correlation between the thickness of the internal and
      external sphincters and sex. The puborectalis and the external anal sphincter
      thickness showed a highly significant positive correlation with age. There was no
      significant correlation between the internal sphincter thickness and age.
      CONCLUSIONS: The endosonographic morphology of children is similar to that of
      adults, although the structures in children less than 5 years of age are
      difficult to differentiate. We detected a significant increase in the thickness
      of the external anal sphincter as patients grow older, but not in the internal
      anal sphincter.

PMID- 19404080
TI  - Biomarkers correlate with colon cancer and risks: a preliminary study.
AB  - PURPOSE: We previously reported that gene expression analysis of biopsies of
      normal-appearing large intestinal mucosa can distinguish individuals with colonic
      cancer and many individuals at risk for colon cancer from controls. The purpose
      of this study was to determine whether noninvasively removed rectal swabs can
      identify individuals with colon cancer or risk of colon cancer as effectively as
      we previously demonstrated using biopsies. METHODS: Rectal mucosa cells were
      removed by rectal swabs, and their gene expression profiles were compared with
      those of biopsies removed by colonoscopy. Expression of 16 genes in the rectal
      mucosa of 12 individuals with colon cancer, 25 with polyps, 37 with family or
      self-reported cancer history, and 23 controls was measured by real-time reverse
      transcription-polymerase chain reaction. RESULTS: We found similar results using
      rectal swabs and biopsies. Groups of individuals with or at risk for cancer
      showed an altered gene expression profile compared with controls. Moreover, each
      of the 12 cancer patients showed altered expression relative to the mean of
      controls. CONCLUSIONS: Gene expression analysis using rectal swabs may provide a
      convenient way to screen for colon cancer.

PMID- 19404081
TI  - Multimedia article. Combined sentinel node biopsy and localized sigmoid resection
      entirely by natural orifice transluminal endoscopic surgery: a new challenge to
      the old paradigm.
AB  - INTRODUCTION: We demonstrate localized sigmoidectomy with sentinel node biopsy
      performed entirely via natural orifice transluminal endoscopic surgery in a
      porcine model (see Video, Supplemental Digital Content 1,
      http://links.lww.com/A1170). METHODS: To perform transluminal endoscopic sentinel
      node biopsy in the sigmoid mesocolon, a conventional double-channel gastroscope
      created both the gastrotomy and pneumoperitoneum enabling peritoneoscopy. The
      sigmoid colon was exposed by an intracolonic magnet under extracorporeal control
      while intraluminal colonoscopy performed lymphatic mapping via submucosal
      injection of methylene blue dye. After searching the mesocolon for blue-stained
      lymph channels, the sentinel nodes were resected and retrieved by the
      intraperitoneal fiberscope. Immediate thereafter localized sigmoidectomy was
      performed via an additional transcolonic access just above the rectosigmoid
      junction. With the circular stapler anvil placed early into the proximal colon,
      mesenteric dissection and proximal transection were performed using conventional
      laparoscopic instruments worked through a long standard trocar passed transanally
      through the colotomy. The specimen was delivered per ano (pull-through technique)
      and the distal margin cross-stapled extracorporeally, including the colotomy
      within the specimen. Stapled intestinal anastomosis was fashioned by passing a
      circular stapler transanally (thus returning the rectal stump to its anatomic
      position) and mating it with the in situ anvil. The gastrotomy was closed as
      previously described. RESULTS: The operative duration was 31.4 minutes and
      technical success was readily achieved. Patency and integrity of the anastomosis
      was confirmed by sigmoidoscopy. CONCLUSION: Oncologically propitious surgery for
      germinal colonic neoplasia may be encompassed by natural orifice transluminal
      endoscopic surgery. This provocative proposal challenges the conventional
      treatment paradigm for early stage colonic neoplasia although much further
      validation of the concepts involved is required.

PMID- 19404083
TI  - Isolated intrathoracic hiatal herniation of the twisted sigmoid colon: report of
      a case.
AB  - The hiatus hernia and sigmoid volvulus are usually found in older patients. The
      delay of the treatment of both of these illnesses may result in increased
      morbidity and mortality. We report a case of an isolated intrathoracic hiatal
      herniation of the twisted sigmoid colon. The patient complained about cramping
      abdominal pain, vomiting, and dyspnea. Chest X-ray and CT scan of the thorax
      showed a distended colonic segment in the posterior mediastinum. The patient
      underwent cruroplasty, Nissen fundoplication, and sigmoid colon resection. This
      is the first report of such a rare case.

PMID- 19404084
TI  - Aggressive phenotype of MYH-associated polyposis with jejunal cancer and intra
      abdominal desmoid tumor: report of a case.
AB  - MYH-associated polyposis is an inherited autosomal recessive disease, linked to
      biallelic germline MYH mutations, which predisposes to the development of
      multiple colorectal adenomas and cancer. The colonic and extracolonic phenotype
      of this syndrome is very heterogeneous. We report the case of a young male
      patient with an aggressive MYH-associated polyposis phenotype. He presented at
      aged 30 years with more than 100 colonic polyps and 4 colonic adenocarcinomas. At
      aged 35 years, Spigelman Stage IV duodenal adenomatosis was detected. When he was
      39 years old, he developed three synchronous jejunal adenocarcinomas and a
      mesenteric desmoid tumor. Based on this report, we believe that screening of the
      entire small bowel should be recommended in MYH-associated polyposis patients,
      especially in those with duodenal adenomas. Similar to patients with familial
      adenomatous polyposis, desmoid tumors also may be part of the clinical spectrum
      of MYH-associated polyposis and may prove to be a significant clinical problem in
      patients submitted to prophylactic colectomy.

PMID- 19404085
TI  - Circular stapler introducer: a novel device to facilitate stapled colorectal
      anastomosis.
AB  - OBJECTIVES: A circular stapler introducer was developed to protect the head of
      the circular stapler and enable atraumatic introduction and advancement of the
      circular stapler without interfering with the application and safety of an
      anastomosis. METHODS: In a Phase I prospective study, we tested the feasibility
      and safety of the novel circular stapler introducer device in 60 consecutive
      patients undergoing left-sided colorectal resections. RESULTS: The median
      distance of the anastomoses from the anal verge was 12 cm (7-20, n = 60). Total
      morbidity was 15 percent. No mortality was observed. Handling of the circular
      stapler introducer was considered nonproblematic by all surgeons who participated
      in the study. No interference of the circular stapler introducer with the
      circular stapling devices used was encountered. The advancement of the stapler
      into the end of the colorectal stump was always possible with the aid of the
      circular stapler introducer. CONCLUSIONS: Use of the circular stapler introducer
      facilitates the double-stapling technique of colorectal anastomosis. The circular
      stapler introducer has great potential and should be tested in larger studies.

PMID- 19404086
TI  - Mosapride and postoperative ileus.

PMID- 19404082
TI  - Prevalence and outcome of anemia after restorative proctocolectomy: a clinical
      literature review.
AB  - PURPOSE: Iron and/or vitamin B12 deficiency anemias, which have adverse effects
      on patients' quality of life, are commonly observed and often overlooked
      complications after restorative proctocolectomy. We performed a systematic review
      of publications on the prevalence of anemia as well as on the impact of anemia on
      a range of clinical, functional, quality of life, and economic outcomes in
      restorative proctocolectomy patients. This information is important to help
      healthcare providers through a comprehensive overview to increase awareness about
      a condition that could require therapy to improve patient healthcare and quality
      of life. METHODS: We reviewed the English language publications on the incidence
      of anemia and its adverse effect after restorative proctocolectomy The United
      States National Library of Medicine database (MEDLINE), the Excerpta Medica
      database (EMBASE), the Cochran Library, and the Google search engine were
      searched for published articles on the prevalence and impact of anemia in post
      restorative proctocolectomy surgical patients. RESULTS: The long-term
      complication most frequently described after RPC is pouchitis. Pouchitis is
      significantly associated with iron deficiency anemia caused by pouch mucosal
      bleeding. Other causes are insufficient and/or impaired iron absorption. It has
      also been observed, however, that restorative proctocolectomy patients with
      underlying familial adenomatous polyposis rarely develop pouchitis yet show
      higher rates of iron deficiency anemia compared to those patients with underlying
      ulcerative colitis. Other causes shown as independent risk factors for iron
      deficiency anemia in restorative proctocolectomy patients are malignancy, desmoid
      tumors, and J-pouch configuration. Vitamin B12 deficiency anemia is also common
      after restorative proctocolectomy. About one-third of restorative proctocolectomy
      patients show abnormal Schilling test and 5 percent have low referenced serum
      cobalamin. It has been observed that the degree resection of the terminal-ileum,
      malabsorption, bacterial overgrowth, and dietary factors are among the known
      causes of cobalamin deficiency. Folate deficiency has not been reported in
      restorative proctocolectomy patients. Describing restorative proctocolectomy
      surgery and its outcomes, in patients without anemia, the quality of life is
      reported excellent regardless of operative technique. CONCLUSIONS: Anemia is not
      uncommon following restorative proctocolectomy and has been shown to have
      negative effects on the patient's quality of life and the economy and may
      substantially increase healthcare costs. The treatment of anemia and its
      underlying causes is important to improving clinical and economic outcomes.

PMID- 19404087
TI  - Nitrergic inhibitory component of rectal response to pelvic nerve stimulation.

PMID- 19404088
TI  - Sacral nerve stimulation and constipation: still a long way to go.

PMID- 19404091
TI  - Adverse effect of BioGlue on the outcome of transanal advancement flap repair.

PMID- 19404092
TI  - Open colectomies vs. laparoscopic colectomies: can we generalize to real-world
      practice settings?

PMID- 19404096
TI  - Dephosphorylation of beta-arrestin 1 in glioblastomas.
AB  - Beta-Arrestins act as signal terminators for G protein-coupled receptors; they
      have also been implicated as scaffolding proteins for Src and mitogen-activated
      protein kinase signaling pathways and transactivators of receptor tyrosine
      kinases, suggesting their possible role in development and oncogenic signaling.
      Dephosphorylation of serine 412 is necessary for Src and mitogen-activated
      protein kinase transactivation. We hypothesized that altered beta-arrestin 1
      phosphorylation and activation status could play a role in gliomagenesis. Using
      monoclonal anti-phospho-(serine 412)- and total beta-arrestin 1 antibodies, we
      performed immunohistochemistry on 126 human glioma samples and 7 nonneoplastic
      controls and Western blot analysis on 5 glioblastomas and 5 nonneoplastic
      controls. We found high constitutive beta-arrestin 1 phosphorylation in
      nonneoplastic brain tissue, particularly in neurons and neuropil. Most Grade II
      and III gliomas retained high beta-arrestin 1 phosphorylation. By contrast, most
      of the glioblastoma samples (58/81) showed nearly complete beta-arrestin 1
      dephosphorylation by immunohistochemistry and decreased relative phosphorylation
      by Western blot. Expression of constitutively activated epidermal growth factor
      receptor vIII in U251 cells caused decreased beta-arrestin 1 phosphorylation
      without altering total beta-arrestin 1 levels. These results suggest that beta
      arrestin 1 dephosphorylation/inactivation is associated with aspects of the
      malignant behavior of glioblastomas.

PMID- 19404101
TI  - Shape memory alloys: metallurgy, biocompatibility, and biomechanics for
      neurosurgical applications.
AB  - SHAPE MEMORY ALLOYS possess distinct dynamic properties with particular
      applications in neurosurgery. Because of their unique physical characteristics,
      these materials are finding increasing application where resiliency,
      conformation, and actuation are needed. Nitinol, the most frequently manufactured
      shape memory alloy, responds to thermal and mechanical stimuli with remarkable
      mechanical properties such as shape memory effect, super-elasticity, and high
      damping capacity. Nitinol has found particular use in the biomedical community
      because of its excellent fatigue resistance and biocompatibility, with special
      interest in neurosurgical applications. The properties of nitinol and its
      diffusionless phase transformations contribute to these unique mechanical
      capabilities. The features of nitinol, particularly its shape memory effect,
      super-elasticity, damping capacity, as well as its biocompatibility and
      biomechanics are discussed herein. Current and future applications of nitinol and
      other shape memory alloys in endovascular, spinal, and minimally invasive
      neurosurgery are introduced. An understanding of the metallurgic properties of
      nitinol provides a foundation for further exploration of its use in neurosurgical
      implant design.

PMID- 19404102
TI  - Virtual temporal bone: an interactive 3-dimensional learning aid for cranial base
      surgery.
AB  - OBJECTIVE: We have developed an interactive virtual model of the temporal bone
      for the training and teaching of cranial base surgery. METHODS: The virtual model
      was based on the tomographic data of the Visible Human Project. The male Visible
      Human's computed tomographic data were volumetrically reconstructed as virtual
      bone tissue, and the individual photographic slices provided the basis for
      segmentation of the middle and inner ear structures, cranial nerves, vessels, and
      brainstem. These structures were created by using outlining and tube editing
      tools, allowing structural modeling either directly on the basis of the
      photographic data or according to information from textbooks and cadaver
      dissections. For training and teaching, the virtual model was accessed in the
      previously described 3-dimensional workspaces of the Dextroscope or Dextrobeam
      (Volume Interactions Pte, Ltd., Singapore), whose interfaces enable volumetric
      exploration from any perspective and provide virtual tools for drilling and
      measuring. RESULTS: We have simulated several cranial base procedures including
      approaches via the floor of the middle fossa and the lateral petrous bone. The
      virtual model suitably illustrated the core facts of anatomic spatial
      relationships while simulating different stages of bone drilling along a variety
      of surgical corridors. The system was used for teaching during training courses
      to plan and discuss operative anatomy and strategies. CONCLUSION: The Virtual
      Temporal Bone and its surrounding 3-dimensional workspace provide an effective
      way to study the essential surgical anatomy of this complex region and to teach
      and train operative strategies, especially when used as an adjunct to cadaver
      dissections.

PMID- 19404103
TI  - Intraoperative computed tomography with integrated navigation system in a
      multidisciplinary operating suite.
AB  - OBJECTIVE: We report our preliminary experience in a prospective series of
      patients with regard to feasibility, work flow, and image quality using a
      multislice computed tomographic (CT) scanner combined with a frameless
      neuronavigation system (NNS). METHODS: A sliding gantry 40-slice CT scanner was
      installed in a preexisting operating room. The scanner was connected to a
      frameless infrared-based NNS. Image data was transferred directly from the
      scanner into the navigation system. This allowed updating of the NNS during
      surgery by automated image registration based on the position of the gantry.
      Intraoperative CT angiography was possible. The patient was positioned on a
      radiolucent operating table that fits within the bore of the gantry. During image
      acquisition, the gantry moved over the patient. This table allowed all positions
      and movements like any normal operating table without compromising the
      positioning of the patient. For cranial surgery, a carbon-made radiolucent head
      clamp was fixed to the table. RESULTS: Experience with the first 230 patients
      confirms the feasibility of intraoperative CT scanning (136 patients with
      intracranial pathology, 94 patients with spinal lesions). After a specific work
      flow, interruption of surgery for intraoperative scanning can be limited to 10 to
      15 minutes in cranial surgery and to 9 minutes in spinal surgery. Intraoperative
      imaging changed the course of surgery in 16 of the 230 cases either because
      control CT scans showed suboptimal screw position (17 of 307 screws, with 9 in 7
      patients requiring correction) or that tumor resection was insufficient (9
      cases). Intraoperative CT angiography has been performed in 7 cases so far with
      good image quality to determine residual flow in an aneurysm. Image quality was
      excellent in spinal and cranial base surgery. CONCLUSION: The system can be
      installed in a preexisting operating environment without the need for special
      surgical instruments. It increases the safety of the patient and the surgeon
      without necessitating a change in the existing surgical protocol and work flow.
      Imaging and updating of the NNS can be performed at any time during surgery with
      very limited time and modification of the surgical setup. Multidisciplinary use
      increases utilization of the system and thus improves the cost-efficiency
      relationship.

PMID- 19404104
TI  - A 3-dimensional computed tomographic procedure for planning retrosigmoid
      craniotomy.
AB  - OBJECTIVE: The planning of retrosigmoid craniotomies often relies on anatomic
      landmarks on the posterolateral surface of the cranium, such as the asterion.
      However, the location of the asterion is not fixed with respect to the underlying
      transverse-sigmoid sinus complex. We introduce a simple procedure that uses 3
      dimensional (3D) computed tomographic imaging to project the transverse-sigmoid
      sinus complex onto the external surface of the cranium. METHODS: We enrolled 8
      patients scheduled for retrosigmoid craniotomy (Group 1) and 30 patients without
      posterior fossa lesions (Group 2). The procedure consists of 3 steps: 1) marking
      the sinus on the internal surface on 3D images of the cranium, 2) transferring
      the marks to the external surface on axial images, and 3) checking the
      transferred marks on the external surface of the cranium on 3D images. RESULTS:
      In Group 1, the craniotomies planned with the aid of our procedure coincided with
      findings made at surgery, indicating the accuracy of our procedure. When we
      applied it in morphometric studies in Group 2, we found that the relative
      location of the transverse-sigmoid sinus junction to the asterion, the superior
      nuchal line, and the posterior edge of the mastoid process exhibited a high
      degree of individual variation. CONCLUSION: Retrosigmoid craniotomy standardized
      according to anatomic landmarks raises the risk for sinus injury because of
      variations in their location. We offer our 3D computed tomographic imaging-based
      procedure as a useful device for the planning of safer retrosigmoid craniotomies.

PMID- 19404105
TI  - Depiction of small veins draining into the vein of galen using preoperative 3
      dimensional navigation in living patients.
AB  - OBJECTIVE: The purpose of this study was to delineate the anatomy of the
      precentral cerebellar vein, superior vermian vein, and internal occipital vein
      using reconstructions of computed tomographic and magnetic resonance imaging
      scans with navigation software. These data were compared with previous anatomic
      and angiographic findings to show the resolution and accuracy of the system.
      METHODS: We retrospectively reviewed 100 patients with intracranial pathologies
      (50 computed tomographic scans with contrast and 50 magnetic resonance imaging
      scans with gadolinium) using a neuronavigation workstation for 3-dimensional
      reconstruction. Particular attention was paid to depiction of the precentral
      cerebellar vein, superior vermian vein, and internal occipital vein. The data
      were reviewed and analyzed. RESULTS: The precentral cerebellar vein, superior
      vermian vein, and its tributary, the supraculminate vein, were depicted in 52
      (52%) patients. The internal occipital vein was delineated on 99 (49.5%) sides
      and joined the basal vein and vein of Galen in 39 (39.4%) and 60 (60.6%)
      hemispheres, respectively. Comparing these results with previous angiographic
      studies, the ability of the neuronavigation system for depicting these vessels is
      similar to that of digital subtraction angiography. CONCLUSION: This study
      illustrates the possibility of depicting the small vessels draining into the
      pineal region venous complex using 3-dimensional neuronavigation with an accuracy
      comparable to that of digital subtraction angiography. This tool provides
      important information for both surgical planning and intraoperative orientation.

PMID- 19404106
TI  - Greater superficial petrosal nerve dissection: back to front or front to back?
AB  - OBJECTIVE: To introduce a novel surgical technique for the dissection of the
      greater superficial petrosal nerve (GSPN) in the middle fossa approach. METHODS:
      Interdural temporal elevation was performed with a front-to-back technique to
      preserve the GSPN in 12 sides of 6 injected cadaveric heads dissected through a
      middle fossa approach. RESULTS: The GSPN emerged from the facial hiatus in a
      shallow bony groove proximally, ran into a deeper sphenopetrosal groove, and
      eventually reached the mandibular nerve. With front-to-back dissection, this
      nerve was easily identified at the posterior border of the mandibular nerve.
      Dissection from front to back minimized the retraction force applied to the
      proximal part of the GSPN, which was preserved in all specimens. CONCLUSION: The
      temporal dura can be elevated safely with a front-to-back technique to preserve
      the GSPN and to help maintain the physiological integrity of the facial nerve.

PMID- 19404107
TI  - Three-dimensional endoscopic pituitary surgery.
AB  - OBJECTIVE: We describe a novel 3-dimensional (3-D) stereoendoscope and discuss
      our early experience using it to provide improved depth perception during
      transsphenoidal pituitary surgery. METHODS: Thirteen patients underwent endonasal
      endoscopic transsphenoidal surgery. A 6.5-, 4.9-, or 4.0-mm, 0- and 30-degree
      rigid 3-D stereoendoscope (Visionsense, Ltd., Petach Tikva, Israel) was used in
      all cases. The endoscope is based on "compound eye" technology, incorporating a
      microarray of lenses. Patients were followed prospectively and compared with a
      matched group of patients who underwent endoscopic surgery with a 2-dimensional
      (2-D) endoscope. Surgeon comfort and/or complaints regarding the endoscope were
      recorded. RESULTS: The 3-D endoscope was used as the sole method of visualization
      to remove 10 pituitary adenomas, 1 cystic xanthogranuloma, 1 metastasis, and 1
      cavernous sinus hemangioma. Improved depth perception without eye strain or
      headache was noted by the surgeons. There were no intraoperative complications.
      All patients without cavernous sinus extension (7of 9 patients) had gross tumor
      removal. There were no significant differences in operative time, length of stay,
      or extent of resection compared with cases in which a 2-D endoscope was used.
      Subjective depth perception was improved compared with standard 2-D scopes.
      CONCLUSION: In this first reported series of purely 3-D endoscopic
      transsphenoidal pituitary surgery, we demonstrate subjectively improved depth
      perception and excellent outcomes with no increase in operative time. Three
      dimensional endoscopes may become the standard tool for minimal access
      neurosurgery.

PMID- 19404109
TI  - Microsurgical management of incompletely coiled and recurrent aneurysms: trends,
      techniques, and observations on coil extrusion.
AB  - OBJECTIVE: With the growing volume of aneurysms treated with endovascular methods
      and the unavoidable risks of incomplete coiling or recurrence, the volume of
      coiled aneurysms requiring surgical management is growing. We present a
      consecutive surgical experience with previously coiled aneurysms to examine
      clinical trends, the phenomenon of coil extrusion, microsurgical techniques, and
      morphological features affecting clippability. METHODS: During a 10-year period,
      43 patients underwent surgical management of an incompletely coiled or recurrent
      aneurysm (Gurian group B). Most patients (88%) presented initially with
      subarachnoid hemorrhage, most commonly (28%) located in the anterior
      communicating artery, and 42% of aneurysms were large or giant sized. RESULTS:
      Twenty-one patients had incompletely coiled aneurysms and 22 patients had
      recurrent aneurysms, with a mean time to recurrence of 28 months. Coil extrusion
      was observed in 1 of the incompletely coiled (5%) and 12 of the recurrent
      aneurysms (55%). Overall, 33 aneurysms were clipped directly, 7 unclippable
      aneurysms were bypassed, and 3 were wrapped. Three patients died (surgical
      mortality, 7%), 1 patient (2%) experienced permanent neurological morbidity, and
      the remaining 39 patients (91%) had good outcomes (mean follow-up, 4.3 years).
      CONCLUSION: This study demonstrated a sharp increase in the incidence of coiled
      aneurysms requiring surgery, reflecting the increasing numbers of patients opting
      for endovascular therapy initially. Coil extrusion occurs more often than
      expected, is often misdiagnosed on angiography as simply compaction, and seems to
      be a time-dependent process not seen acutely. Direct clipping is the preferred
      microsurgical treatment of coiled aneurysms and may be predicted by the
      relationship between coil width and compaction height (C/H < 2.5, or a wedge
      angle < 90 degrees). We recommend a bypass strategy for unclippable coiled
      aneurysms because it can be executed methodically; has predictable ischemia
      times; and is associated with more favorable results than thrombectomy, coil
      extraction, and clip reconstruction.

PMID- 19404108
TI  - Cavernous hemangioma of the mesencephalon: tonsillouveal transaqueductal
      approach.
AB  - OBJECTIVE: Recent advances in microsurgical techniques facilitate surgical
      resection of brainstem lesions that were previously considered inoperable. In
      this article we present, for the first time, the tonsillouveal transaqueductal
      approach to access a progressively symptomatic cavernoma within the depth of the
      tegmentum of the mesencephalon. METHODS: A 52-year-old woman presented with a
      history of slowly progressive right-sided hemiparesis and ataxia. On magnetic
      resonance imaging, a relatively large cavernoma involving the tegmentum of the
      mesencephalon was shown. The sylvian aqueduct was patent and there was no
      secondary ventriculomegaly. The patient underwent surgery via a suboccipital
      craniotomy and C1 laminectomy. The right tonsillouveal and medullotonsillar
      spaces were opened to the level of the choroidal point of the posteroinferior
      cerebellar artery. The tela choroidea was incised from the foramen of Magendie to
      the telovelar junction. Looking through the aqueduct and at a point 5 mm superior
      to its inferior inlet, there was a small cherry-like blister protruding into the
      aqueductal anterior surface. This was used as an entry point to access the
      cavernoma. The space around the cavernoma was gently dissected and the cavernoma
      was circumferentially coagulated to shrink it in a concentric manner toward its
      center. RESULTS: The total removal of the lesion was achieved and the
      histopathological findings were consistent with a cavernoma. As a result of
      noncommunicating hydrocephalus, the patient needed a ventriculoperitoneal shunt.
      The 1-year postoperative neurological examination was consistent with
      preoperative findings. CONCLUSION: This report shows, for the first time, direct
      surgical removal of a cavernous hemangioma in the mesencephalic tegmentum via the
      aqueduct. This approach adds to contemporary microneurosurgery, respecting
      functional anatomy and minimizing neurological deficits.

PMID- 19404110
TI  - Anatomy of the superior ophthalmic vein approach for direct endovascular access
      to vascular lesions of the orbit and cavernous sinus.
AB  - OBJECTIVE: The superior ophthalmic vein (SOV) provides an alternative venous
      access for the treatment of carotid-cavernous fistulae. Its direct surgical
      exposure and cannulation can be difficult. This study was performed to identify
      anatomic landmarks to facilitate localization and exposure of the SOV. METHODS:
      The vascular tree of 6 formalin-fixed human cadaveric heads was injected with
      colored silicone. The SOV was exposed using a periorbital incision. The diameter
      of the SOV, its distance to the inferior border of the incision, and the angle
      formed by the SOV and sagittal midpupillary line were measured. The tributaries
      of the SOV and its orbital anatomy and relationship to the supraorbital
      notch/foramen were evaluated. RESULTS: The SOV was located in the superomedial
      quadrant of the orbit. Its mean diameter was 2.2 mm (standard deviation, +/-1.2
      mm). The mean distance from the SOV to the superior sulcus of the eyelid nasally
      was 5.9 mm (standard deviation, +/-2.0 mm). The mean angle formed by the SOV and
      the sagittal midpupillary line was 27.9 degrees (standard deviation, +/-5.4
      degrees). The tributaries of the SOV were the angular vein and supraorbital vein
      (SPOV). The SPOV, identified in all 12 dissections, could be followed to the SOV
      within the orbit. The SPOV was always located inside the supraorbital
      notch/foramen when the latter was present. CONCLUSION: The SOV is located at the
      superomedial quadrant of the orbit. The SPOV is a reliable reference during
      surgical exposure. A lid crease or subbrow incision centered over the
      supraorbital notch simplifies identification of the SOV.

PMID- 19404111
TI  - Transciliary orbitofrontozygomatic approach to lesions of the anterior cranial
      fossa.
AB  - OBJECTIVE: Several variations on the supraorbital craniotomy via a forehead or
      eyebrow incision have been described in the literature in recent years. A
      modification of this approach, the transciliary orbitofrontozygomatic approach,
      has been used by the authors as a minimally invasive method of approaching
      certain intracranial pathologies. The authors present their experience with this
      technique in 105 consecutive patients with tumors or aneurysms of the anterior
      cranial fossa. METHODS: A transciliary keyhole approach was used in all cases.
      From June 1998 to June 2005, 37 tumors, 1 cavernous malformation, and 77 anterior
      circulation aneurysms were treated (67 females, 38 males; age range, 8-77 years)
      with an orbitofrontozygomatic approach via an eyebrow incision. Patients were
      followed by the authors at a single institution for 1 year postoperatively.
      RESULTS: Of the 105 patients treated with a transciliary orbitofrontozygomatic
      approach, 2 (1.9%) developed a cerebrospinal leak. Two other patients (1.9%) very
      early in the series had persistent forehead asymmetry at 1 year postoperatively.
      Two patients who underwent surgery for a ruptured aneurysm experienced an
      intraoperative rupture, which was thought to be unrelated to the exposure. None
      of the operations had to be converted to a pterional craniotomy. CONCLUSION: This
      approach was used in 105 consecutive patients who underwent operation for either
      tumors or aneurysms via an eyebrow incision. The transciliary
      orbitofrontozygomatic approach is associated with low surgical morbidity.
      Although experience with this technique is still limited, it is a viable
      alternative in cases in which the pathology resides in the midline or anterior
      fossa.

PMID- 19404112
TI  - Translaminar versus pedicle screw fixation of C2: comparison of surgical
      morbidity and accuracy of 313 consecutive screws.
AB  - OBJECTIVE: C2 translaminar (TL) screws rigidly capture the posterior elements of
      C2, avoid risk of vertebral artery injury, and are less technically demanding
      than C2 pedicle (PD) screws. However, a C2-TL screw breach places the spinal cord
      at risk, and the durability of C2-TL screws remains unknown. It is unclear if TL
      versus PD screw fixation of C2 is truly associated with less operative morbidity,
      greater accuracy of screw placement, or equivalent durability. METHODS: We
      retrospectively reviewed the records of 167 consecutive patients undergoing
      posterior cervical fusion with either PD or TL screw fixation of C2.
      Perioperative morbidity, breach of the C2 lamina or pedicle on postoperative
      computed tomographic scans, and rates of operative revision were compared between
      PD and TL screw constructs in axial (C1-C2 or C1-C3) and subaxial (C2 and caudal)
      cervical fusions. RESULTS: In total, 152 C2-TL screws and 161 C2-PD screws were
      placed in 167 patients. Thirty-one (19%) cases of axial cervical fusion (C1-C2 or
      C1-C3) were performed (mean age, 63.8 +/- 20.6 years) with either C2-TL (16
      [52%]) or C2-PD (15 [48%]) screw fixation. One hundred thirty-six (81%) cases of
      subaxial cervical fusion (C2-caudal) were performed (mean age, 57.9 +/- 14.7
      years) with either C2-TL (66 [49%]) or C2-PD (70 [51%]) screw fixation. For both
      axial and subaxial cervical fusions, baseline patient characteristics and all
      measures of perioperative morbidity were similar between C2-TL and C2-PD screw
      cohorts. In total, 11 (7%) PD screws breached the pedicle (0 requiring acute
      revision) versus only 2 (1.3%) TL screws that breached the C2 lamina (1 requiring
      acute revision) (P = 0.018). By 1 year postoperatively, pseudoarthrosis or screw
      pullout requiring reoperation was required in 4 (6.1%) patients with C2-TL screws
      versus 0 (0%) patients with PD screws (P < 0.05 for subaxial constructs). No
      cases of C2-TL or C2-PD axial fusion required reoperation or screw pullout or
      pseudoarthrosis. CONCLUSION: In our experience, radiographic breach of C2 pedicle
      screws occurred more frequently than C2 laminar screw breach. However, this was
      not associated with an increase in morbidity. By 12 months postoperatively, C2-TL
      screws were associated with a greater incidence of operative revision when used
      in subaxial constructs but similarly effective for axial cervical constructs. The
      1-year durability of C2-TL screws might be inferior to C2 pedicle screws for
      subaxial fusions, but equally effective for axial cervical fusions.

PMID- 19404113
TI  - Open kyphoplasty for management of severe osteoporotic spinal fractures.
AB  - OBJECTIVE: Osteoporotic compression fractures, which can lead to neurological
      complications in some cases, are an increasingly frequent occurrence. These
      lesions require decompression surgery with or without spinal stabilization
      procedures. In this article, we present the preliminary results obtained using
      open kyphoplasty, a new method of treating vertebral compression disorders.
      METHODS: Sixteen patients were included in this prospective study, and a total of
      17 vertebrae were treated. All of the patients had vertebral compression
      fractures associated with neurological disorders. The surgical treatment
      consisted of open kyphoplasty after laminectomy and decompression. Short-segment
      vertebral osteosynthesis was also performed in patients with pronounced local
      kyphosis. Pain was rated at clinical assessments, and radiological assessments
      were performed to determine the restored vertebral height and the correction of
      any local vertebral kyphosis. RESULTS: Analysis of the results obtained using
      this method showed that vertebral height was significantly improved (P < 0.001)
      and local kyphosis was significantly reduced (P < 0.001). The mean operating time
      was 90 minutes. The neurological status of all patients improved; 14 patients
      recovered completely from their neurological symptoms. The last 2 patients had
      associated neurological disease but were able to walk. There were 2 superficial
      postoperative infections. CONCLUSION: This method for treating severe
      osteoporotic compression fractures associated with neurological disorders gives
      successful results and can be used to treat neurological compression fractures
      while consolidating the vertebral body. Therefore, this less invasive approach
      seems to be particularly useful for treating compression fractures in the
      thoracolumbar spine junction in elderly patients who often have comorbidities.

PMID- 19404114
TI  - Primary dural repair during minimally invasive microdiscectomy using standard
      operating room instruments.
AB  - OBJECTIVE: Minimally invasive microdiscectomies are commonly being performed for
      disc herniations. Although inadvertent dural tears are not common, they do occur.
      Present management of many dural tears includes fibrin glue or other adhesive
      substances over the dura, tight closure of the fascia and skin, and possibly
      bedrest. Because these surgeries are usually performed through a small tube, a
      primary dural repair can be prohibitively difficult. One reason for the
      difficulty in a primary closure is that the small tube limits the use of proper
      opening and closing of standard dural repair instruments as well as the proper
      angulation of the instruments. METHODS: To circumvent this difficulty, we have
      improvised using commonly available instruments in the operating room for primary
      dural closure. RESULTS: We describe our technique and present a video
      demonstrating the method of primary dural closure without custom-made
      instruments. CONCLUSION: Primary dual repair during minimally invasive
      microdiscectomy can be performed using standard operation room instruments,
      including a standard micropituitary ronguer, 5-0 Prolene suture (Ethicon, Inc.,
      Somerville, NJ), and a laparoscopic knot pusher.

PMID- 19404115
TI  - Pediatric sural nerve harvest: a fully endoscopic technique.
AB  - OBJECTIVE: The sural nerve has long been a favorite for peripheral nerve repair.
      Traditional "stocking seam" and "stair-step" harvest techniques both have serious
      drawbacks, including unsightly scarring with contractures occasionally leading to
      equinovarus deformities, long operative time, and poor quality and length of
      graft. Our objective was to develop a truly endoscopic method of sural nerve
      harvest using 1 small incision and 1 stab incision. METHODS: An endoscope
      designed for harvesting vascular conduits was used for nerve graft dissection.
      The nerve was then cut through a stab incision below the popliteal fossa. Sural
      nerve harvest was performed on 3 pediatric patients, aged 5 months to 3.5 years,
      between October and December of 2007. RESULTS: Nerve graft lengths were 9.5 to 13
      cm. The mean operative time was 18 minutes from incision to graft removal and 36
      minutes from incision to dressing placement. During all procedures, the brachial
      plexus exploration proceeded unimpeded during the graft harvest. Under
      microscopic inspection, the nerve grafts were much less damaged than those
      harvested previously with the stair-step technique. There were no complications
      during a mean follow-up period of 3 months. CONCLUSION: Advantages over
      previously described techniques include: 1) reduction from three or four 1.5-cm
      incisions to one 1.5-cm incision and one 3-mm incision, 2) a significant decrease
      in operative time, 3) increased ease of performing the graft harvest
      simultaneously with the brachial plexus dissection, and 4) a notable improvement
      in the graft, both in length and appearance.

PMID- 19404116
TI  - VarioGuide: a new frameless image-guided stereotactic system--accuracy study and
      clinical assessment.
AB  - OBJECTIVE: VarioGuide (BrainLAB AG, Feldkirchen, Germany) is a new system for
      frameless image-guided stereotaxy. In the present study, we aimed to assess
      target point accuracy in a laboratory setting and the clinical feasibility of the
      system. METHODS: Using the phantom of our frame-based stereotactic system
      (Riechert-Mundinger; Inomed Medizintechnik GmbH, Teningen, Germany), target
      points were approached from different angles with the frameless system. Target
      point deviation in the x, y, and z planes was assessed. Furthermore, patients
      harboring intracranial lesions were diagnostically biopsied using VarioGuide.
      RESULTS: Phantom-based accuracy measurements yielded a mean target point
      deviation of 0.7 mm. Between February 2007 and April 2008, 27 patients were
      diagnostically biopsied. Lesion volumes ranged from 0.2 to 117.6 cm3, trajectory
      length ranged from 25.3 to 64.1 mm, and the diagnostic yield was 93%. CONCLUSION:
      Concluding from the phantom measurements with ideal image-object registration,
      assumed spherical lesions with a volume of 0.524 cm can be biopsied with 100%
      target localization. Early clinical data revealed VarioGuide to be safe and
      accurate for lesions of 0.2 cm3 and larger. Thereby, the system seems feasible
      for the biopsy of most intracranial lesions.

PMID- 19404117
TI  - Isolation of the brain-related factor of the error between intended and achieved
      position of deep brain stimulation electrodes implanted into the subthalamic
      nucleus for the treatment of Parkinson's disease.
AB  - OBJECTIVE: Although a few studies have quantified errors in the implantation of
      deep brain stimulation electrodes into the subthalamic nucleus (STN), a
      significant trend in error direction has not been reported. We have previously
      found that an error in axial plane, which is of most concern because it cannot be
      compensated for during deep brain stimulation programming, had a posteromedial
      trend. We hypothesized that this trend results from a predominance of a
      directionally oriented error factor of brain origin. Accordingly, elimination of
      nonbrain (technical) error factors could augment this trend. Thus, implantation
      accuracy could be improved by anterolateral compensation during target planning.
      METHODS: Surgical technique was revised to minimize technical error factors.
      During 22 implantations, targets were selected on axial magnetic resonance
      imaging scans up to 1.5 mm anterolateral from the STN center. Using fusion of
      postoperative computed tomographic and preoperative magnetic resonance imaging
      scans, implantation errors in the axial plane were obtained and compared with
      distances from the lead to the STN to evaluate the benefit of anterolateral
      compensation. RESULTS: Twenty errors and the mean error had a posteromedial
      direction. The average distances from the lead to the target and to the STN were
      1.7 mm (range, 0.8-3.1 mm) and 1.1 mm (range, 0.1-1.9 mm), respectively. The
      difference between the 2 distances was significant (paired t test, P < 0.0001).
      The lower parts of the lead were consistently bent in the posteromedial direction
      on postoperative scout computed tomographic scans, suggesting that a brain
      related factor is responsible for the reported error. CONCLUSION: Elimination of
      the technical factors of error during STN deep brain stimulation implantation can
      result in a consistent posteromedial error. Implantation accuracy may be improved
      by compensation for this error in advance.

PMID- 19404118
TI  - Microsurgical and endoscopic anatomy of the vidian canal.
AB  - OBJECTIVE: The vidian canal, the conduit through the sphenoid bone for the vidian
      nerve and artery, has become an important landmark in surgical approaches to the
      cranial base. The objective of this study was to examine the anatomic features of
      the vidian canal, nerve, and artery, as well as the clinical implications of our
      findings. METHODS: Ten adult cadaveric specimens and 10 dried skulls provided 40
      vidian canals for examination with x 3 to x 20 magnification and the endoscope.
      RESULTS: The paired vidian canals are located in the skull base along the line of
      fusion of the pterygoid process and body of the sphenoid bone. The canal opens
      anteriorly into the medial part of the pterygopalatine fossa and posteriorly at
      the upper part of the anterolateral edge of the foramen lacerum. The vidian
      nerve, when followed posteriorly, reaches the lateral surface of the anterior
      genu of the petrous carotid and the anteromedial part of the cavernous sinus
      where the nerve is continuous with the greater petrosal nerve. The bone
      surrounding the upper part of 12 of 20 vidian canals protruded into the floor of
      the sphenoid sinus and one canal had a bony dehiscence that exposed its contents
      under the sinus mucosa. Nine petrous carotid arteries (45%) gave rise to a vidian
      artery, all of which anastomosed with the vidian branch of the maxillary artery
      in the vidian canal or pterygopalatine fossa. The vidian canal can be exposed by
      opening the floor of the sphenoid sinus, the posterior wall of the maxillary, the
      posterior part of the lateral wall of the nasal cavity, and the medial part of
      the floor of the middle fossa. CONCLUSION: The vidian canal and nerve are
      important landmarks in accessing the anterior genu of the petrous carotid,
      anteromedial part of the cavernous sinus, and petrous apex.

PMID- 19404119
TI  - Microscopic and endoscopic extracranial approaches to the cavernous sinus:
      anatomic study.
AB  - OBJECTIVE: In the past 2 decades, various extracranial approaches to the
      cavernous sinus (CS), using either microscopic or endoscopic techniques, have
      been described. The aim of this study was to describe the distinctive anatomic
      features of these approaches and compare their efficacy in exposing the sella and
      parasellar areas. METHODS: Ten adult cadaver heads with red latex injected in the
      arterial system were used. Five different approaches were performed: 1) endonasal
      microscopic transsphenoidal approach; 2) sublabial microscopic transsphenoidal
      approach, including its variation described by Fraioli et al. ; 3) transmaxillary
      microscopic approach; 4) paraseptal endoscopic transsphenoidal approach; and 5)
      transethmoid-pterygoid-sphenoidal endoscopic approach. The CS exposition was
      evaluated for each approach and a grading system, which considers surgical
      maneuverability as well as visualization, was used. RESULTS: The medial CS
      compartment is well exposed with all endoscopic and microscopic transsphenoidal
      approaches, but it is insufficiently exposed with the transmaxillary approach.
      The variation to the sublabial microscopic approach suggested by Fraioli et al.
      allows its widest microsurgical exposure. The lateral compartment is well
      visualized with the transmaxillary microscopic and the endoscopic approaches. The
      major anatomic structures that can limit exposure of the CS lateral compartment
      are the posterior ethmoid and medial pterygoid process. CONCLUSION: The sublabial
      transsphenoidal microscopic approach, with its variations, allows the most
      versatile extracranial microscopic exposure of the sella and CS. The paraseptal,
      binostril endoscopic approach allows a very good exposure of the CS; the
      transethmoid-pterygoid-sphenoidal endoscopic approach achieves the best
      maneuverability in the lateral compartment of the CS.

PMID- 19404120
TI  - Anatomic study of the infraorbital foramen for radiofrequency neurotomy of the
      infraorbital nerve.
AB  - OBJECTIVE: To examine the anatomy of the infraorbital canal and foramen and the
      angles at which a radiofrequency probe must be directed to enter the infraorbital
      foramen and canal, as a guide to performing radiofrequency ablation of the
      infraorbital nerve in patients with relative or absolute contraindications to
      lesions of the trigeminal ganglion or posterior root. METHODS: Eleven cadaveric
      skulls were studied. The infraorbital nerve, after passing through the
      infraorbital foramen, enters the infraorbital canal and groove in the floor of
      the orbit before reaching the foramen rotundum. Small probes were placed through
      the foramen into the infraorbital canal, and pictures were taken in the
      anteroposterior and sagittal planes. The pictures were analyzed using the
      ImageTool program (University of Texas Health Science Center, San Antonio, TX) to
      calculate the anteroposterior and sagittal angles of the probe. The distances of
      the foramen from the midline, lateral edge of the anterior nasal aperture, and
      inferior orbital rim were examined. RESULTS: A probe introduced through the cheek
      from below and medial to the foramen and directed upward and laterally at an
      angle of approximately 22 degrees in the coronal plane and 120 degrees in the
      sagittal plane toward a point approximately 26 mm from the midline and 8 mm below
      the inferior orbital rim will penetrate the infraorbital foramen for placement of
      the probe's tip in the infraorbital canal. CONCLUSION: The coordinates for
      placement of the radiofrequency probe through the infraorbital foramen and into
      the infraorbital canal are reviewed, along with a discussion of pitfalls in
      radiofrequency ablation of the nerve.

PMID- 19404121
TI  - Jugular tubercle and vertebral artery/posterior inferior cerebellar artery
      anatomic relationship: a 3-dimensional angiography computed tomography
      anthropometric study.
AB  - OBJECTIVE: To evaluate structural variations of the jugular tubercles (JTs) and
      their relationships with the vertebral artery, the posterior inferior cerebellar
      artery (PICA), and the vertebrobasilar junction (VBJ). METHODS: The depth,
      height, and width of the JTs were measured using 30 cadaveric basicranial
      specimens and 50 three-dimensional angiography computed tomographic (angio-CT)
      scans evaluating morphological variations between the 2 sides. Angio-CT analysis
      evaluated the relationships of the JTs with the vertebral arteries and the PICAs.
      The location of the VBJ with respect to the JT level in the coronal plane was
      evaluated. RESULTS: In the cadaveric specimens, the mean JT depth ranged from 0.9
      to 3.1 cm, the mean height ranged from 0.6 to 1.5 cm, and the mean width ranged
      from 0.4 to 1.2 cm. According to the 3-dimensional angio-CT scans, JT
      measurements ranged as follows: depth, 0.7 to 2.6 cm; height, 0.6 to 1.4 cm; and
      width, 0.3 to 1.2 cm. The vertebral artery was in close contact with the JT on
      the left side in 30% of cases and on the right side in 24% of the cases. On axial
      scans, the PICA origin was classified as anterior to the JT in 20.5% of patients
      on the left side and 17.4% on the right, at the JT level in 50% of patients on
      the left side and 45.7% on the right, and posterior to the JT in 29.5% of
      patients on the left side and 36.9% on the right. On coronal scans, the PICA
      origin was classified as superior to the JT in 13.6% of patients on the left side
      and 8.7% on the right, at the JT level in 54.6% of patients on the left side and
      50% on the right, and inferior to the JT in 31.8% of patients on the left side
      and 41.3% on the right. In the coronal plane, the VBJ was located above the
      tubercles in 16 patients (32%), at the JT level in 28 patients (56%), and below
      the tubercles in 6 patients (12%). CONCLUSION: A precise morphometric analysis of
      the JTs on 3-dimensional CT scans was quick and safe and showed significant
      variations in their size and shape. The relationship of the JT with vertebral
      artery and the PICA varied significantly, as well as with the VBJ location.
      Knowledge of these morphological variations can contribute to optimal
      preoperative surgical planning, minimizing retraction and reducing morbidity
      during extreme lateral infrajugular-transtubercular exposure surgery.

PMID- 19404122
TI  - Endoscopic image-guided transoral approach to the craniovertebral junction: an
      anatomic study comparing surgical exposure and surgical freedom obtained with the
      endoscope and the operating microscope.
AB  - OBJECTIVE: The transoral approach is the most direct and commonly used method to
      access the ventral craniocervical junction. Recently, an endonasal, endoscopic
      approach to the craniovertebral junction was proposed. We reasoned that the
      coupling of the endoscope with the direct transoral approach and image guidance
      could result in a minimally invasive, simple approach to the ventral
      craniovertebral junction. We investigated the potential usefulness of such an
      approach in a cadaver model. METHODS: A direct transoral approach to the
      craniovertebral junction was performed using computed tomography-based image
      guidance in 9 fresh adult head specimens. Endoscopic odontoidectomy was performed
      in 5 specimens. In the remaining 4 specimens, the surgical working area and
      surgical freedom associated with an endoscopic and a microscopic approach to the
      ventral craniovertebral junction were evaluated and compared. In these 4
      specimens, we also measured and compared the exposure of the clivus provided by
      the endoscope and by the operating microscope without splitting the soft palate.
      RESULTS: With variously angled endoscopic assistance and image guidance, it was
      possible to tailor the excision of the anterior arch of the atlas and to
      precisely identify the odontoid process and its related ligaments
      intraoperatively, resulting in a complete and controlled odontoidectomy. The
      surgical area exposed over the posterior pharyngeal wall was significantly
      improved using the endoscope (606.5 +/- 127.4 mm3) compared with the operating
      microscope (425.7 +/- 100.8 mm3), without any compromise of surgical freedom (P <
      0.05). The extent of the clivus exposed with the endoscope (9.5 +/- 0.7 mm)
      without splitting the soft palate was significantly improved compared with that
      associated with microscopic approach (2.0 +/- 0.4 mm) (P < 0.05). CONCLUSION:
      With the aid of the endoscope and image guidance, it is possible to approach the
      ventral craniovertebral junction transorally with minimal tissue dissection, no
      palatal splitting, and no compromise of surgical freedom. In addition, the use of
      an angled-lens endoscope can significantly improve the exposure of the clivus
      without splitting the soft palate. An endoscope-assisted transoral approach is a
      direct and powerful tool for the treatment of surgical pathology at the
      craniovertebral junction.

PMID- 19404123
TI  - Gamma knife radiosurgery-induced cavernous hemangioma: case report.
AB  - OBJECTIVE: We report a rare case of gamma knife radiation-induced cavernous
      hemangioma. CLINICAL PRESENTATION: A 35-year-old man underwent resection of a
      left vestibular schwannoma and gamma knife radiosurgery (maximal dose, 24 Gy;
      marginal dose, 12 Gy) for the residual schwannoma. Follow-up magnetic resonance
      images showed no tumor progression. Ten years later, he developed right
      hemihyperesthesia and mild hemiparesis. Magnetic resonance imaging revealed a
      size reduction at the resected tumor site and a newly developed lesion in the
      adjacent pons. No connection was observed between the new mass and the previous
      tumor. The T2-weighted image showed the new mass as heterogeneous and "popcorn
      like" with a mixed signal intensity core and a hypointense hemosiderin rim. Two
      years after its appearance, the new lesion appeared hypointense on the T2
      weighted image, with a hyperintense core on the T1-weighted image. These findings
      were compatible with cavernous hemangioma. INTERVENTION: We diagnosed the new
      lesion as a radiation-induced cavernous hemangioma. Ten days after admission,
      symptoms improved without surgical intervention. CONCLUSION: Gamma knife
      radiosurgery induced this rare case of cavernous hemangioma in an area that
      received a low dose of irradiation and was distant from the primary tumor.
      Because patients undergoing radiosurgery face the possibility, although small,
      that such neoplasms may occur, they should be followed for many years.

PMID- 19404124
TI  - Large distal anterior cerebral artery aneurysm treated with resection and
      interposition graft: case report.
AB  - OBJECTIVE: Distal anterior cerebral artery (DACA) aneurysms are rare,
      representing only 2% to 6.7% of all intracranial aneurysms. Most of them are
      small. Large and giant aneurysms are even rarer in this location. Only 26 giant
      pericallosal (PC) aneurysms have been reported thus far. Various surgical
      techniques have been used to treat these aneurysms, including direct aneurysm
      neck clipping, aneurysm trapping, proximal occlusion of the anterior cerebral
      artery, or a combination of clipping with coiling or a bypass procedure. The
      report presents an unusual case of a complex DACA aneurysm managed by resection
      and interposition arterial graft. CLINICAL PRESENTATION: A 69-year-old woman
      presented with acute onset of a severe headache. A digital subtraction angiogram
      showed a partially thrombosed, complex broad-necked A2-A3 junction aneurysm
      involving the origin of PC and callosomarginal vessels with a probability of a
      dissection of the DACA. The left PC artery was significantly narrowed. Because of
      the complex neck and involvement of the origin of PC and callosomarginal
      arteries, endovascular treatment was not possible, and microsurgical treatment
      was planned. TECHNIQUE: A large, partially thrombosed, and fusiform anterior
      cerebral artery A2-A3 aneurysm, with evidence of previous bleeding, was found and
      treated with resection and a short interposition graft using a segment of the
      superficial temporal artery. CONCLUSION: Surgical treatment of a large DACA
      aneurysm may be difficult due to a complex neck and the involvement of the branch
      vessels. Resection and interposition grafting and A3-A3 or A4-A4 anastomoses are
      treatment options for such patients.

PMID- 19404126
TI  - Spontaneous delayed proximal migration of enterprise stent after staged treatment
      of wide-necked basilar aneurysm: technical case report.
AB  - OBJECTIVE: To document a unique technical issue with a relatively newly released
      intravascular stent used for adjunctive treatment of wide-necked cerebral
      aneurysms. CLINICAL PRESENTATION: A 48-year-old woman with a sister who had a
      large unruptured wide-necked basilar aneurysm underwent screening evaluation that
      revealed a nearly identical aneurysm. She also harbored small unruptured right
      superior cerebellar and left anterior cerebral artery aneurysms. INTERVENTION:
      Endovascular treatment of the 11.5-mm basilar aneurysm was performed in a staged
      manner. Stent placement was performed first, followed by delayed coil
      embolization of the aneurysm 9 weeks later. Follow-up angiography at the time of
      the second procedure revealed significant spontaneous proximal migration of the
      Enterprise Vascular Reconstruction Device and Delivery System (Cordis
      Neurovascular, Inc., Miami Lakes, FL) with the distal extent of the device
      migrating from the right P2 segment into the neck of the aneurysm. Coil
      embolization was performed despite migration of the vascular reconstruction
      device. CONCLUSION: The use of stents in the endovascular treatment of cerebral
      aneurysms has vastly improved our ability to treat complex lesions. Technical
      issues remain with these devices, and description of this event may alter the way
      we use the Enterprise Vascular Reconstruction Device and Delivery System in terms
      of staging procedures, and when evaluating the particular vascular anatomy of the
      individual patient with special attention to parent artery vessel size.

PMID- 19404125
TI  - Rupture of a spinal artery aneurysm attributable to exacerbated Sjogren syndrome:
      case report.
AB  - OBJECTIVE: Presentation of a patient with acute subarachnoid hemorrhage from a
      ruptured spinal artery aneurysm attributable to exacerbated Sjogren syndrome.
      CLINICAL PRESENTATION: A 46-year-old woman with symptoms of exacerbated Sjogren
      syndrome experienced the acute onset of extreme headache accompanied by nuchal
      rigidity. INTERVENTION: A computed tomographic scan revealed subarachnoid
      hemorrhage. Angiography showed an isolated aneurysm of a branch of the right
      vertebral artery that was a feeding artery of the anterior spinal artery. Neither
      operative clipping nor endovascular coiling of the aneurysm was reasonable, owing
      to the high risk of occluding the anterior spinal artery during the intervention.
      Further diagnostic measures confirmed Sjogren syndrome and revealed
      cryoglobulinemic vasculitis, membranoproliferative glomerulonephritis with acute
      renal failure, Hashimoto thyroiditis, and acute hydrocephalus. In the course of
      conservative treatment, the patient recovered completely from the subarachnoid
      hemorrhage. One year after treatment with glucocorticoids and immunosuppressive
      agents, both the aneurysm and the vasculitis could no longer be detected on
      conventional angiography. CONCLUSION: Generally, spinal artery aneurysms are
      exceptionally rare, and few cases of rupture with subsequent subarachnoid
      hemorrhage have been published. We report on a ruptured spinal aneurysm
      attributable to Sjogren syndrome-associated cryoglobulinemic vasculitis.
      Conservative treatment with glucocorticoids and immunosuppressive agents led to
      resolution of the vasculitic spinal aneurysm.

PMID- 19404127
TI  - Brainstem cavernous malformations.
AB  - Brainstem cavernous malformations (CMs) continue to present a considerable source
      of controversy in the neurosurgical community, with an accumulating volume of
      literature detailing their natural history and their surgical and radiosurgical
      management. As part of a systematic review of the literature, 12 natural history
      studies, 52 surgical series, and 14 radiosurgical series were tabulated. Annual
      bleeding rates for brainstem CMs ranged from 2.3% to 4.1% in natural history
      studies and from 2.68% to 6.8% in surgical series before intervention. Rebleed
      rates as high as 21.5% in natural history studies and greater than once per year
      in surgical series were reported. A total of 684 of 745 CMs (92%) were documented
      as completely resected in 46 series that provided specific information on
      resection rates. Early postoperative morbidity ranged from 29% to 67% in larger
      surgical series, although it was often transient. Thirty of 61 partially resected
      lesions rebled; 4 of these rebleeds were fatal. Twelve additional patients died
      from surgically related causes for a combined postoperative rebleeding and
      surgically related mortality rate of 1.9%. Across 45 series (683 patients), 85%
      of patients were reported as the same or improved, 14% were worse, and 1.9% died
      from surgically related causes at long-term follow-up. Patients with
      anterolateral pontine lesions generally appeared to have a better functional
      recovery, whereas those requiring excision via the floor of the fourth ventricle
      had relatively worse long-term outcomes. Radiosurgical series demonstrated
      conflicting data; some reported a statistically significant decrease in CM
      rebleeding rates after 2 years, whereas others did not, partially related to
      dosimetry. Postradiosurgical morbidity was nonetheless significantly greater for
      CMs than for arteriovenous malformations.

PMID- 19404129
TI  - General anesthesia versus local anesthesia for carotid surgery.

PMID- 19404128
TI  - Evaluation of Onyx HD-500 embolic system in the treatment of 84 wide-neck
      intracranial aneurysms.
AB  - OBJECTIVE: We report our results using Onyx HD-500 (Micro Therapeutics, Inc.,
      Irvine, CA) in the endovascular treatment of wide-neck intracranial aneurysms,
      which have a high rate of incomplete occlusion and recanalization with platinum
      coils. METHODS: Sixty-nine patients with 84 aneurysms were treated. Most of the
      aneurysms were located in the anterior circulation (80 of 84 aneurysms), were
      unruptured (74 of 84 aneurysms), and were incidental. Ten presented with
      subarachnoid hemorrhage, and 15 were symptomatic. All aneurysms had wide necks
      (neck >4 mm and/or dome-to-neck ratio <1.5). Fifty aneurysms were small (<12 mm),
      30 were large (12 to <25 mm) and 4 were giant. Angiographic follow-up was
      available for 65 of the 84 aneurysms at 6 months, for 31 of the 84 aneurysms at
      18 months, and for 5 of the 84 aneurysms at 36 months. RESULTS: Complete aneurysm
      occlusion was seen in 65.5% of aneurysms on immediate control, in 84.6% at 6
      months, and in 90.3% at 18 months. The rates of complete occlusion were 74%,
      95.1%, and 95.2% for small aneurysms and 53.3%, 70%, and 80% for large aneurysms
      at the same follow-up periods. Progression from incomplete to complete occlusion
      was seen in 68.2% of all aneurysms, with a higher percentage in small aneurysms
      (90.9%). Aneurysm recanalization was observed in 3 patients (4.6%), with
      retreatment in 2 patients (3.3%). Procedural mortality was 2.9%. Overall
      morbidity was 7.2%. CONCLUSION: Onyx embolization of intracranial wide-neck
      aneurysms is safe and effective. Morbidity and mortality rates are similar to
      those of other current endovascular techniques. Larger samples and longer follow
      up periods are necessary.

PMID- 19404130
TI  - From mutant mice to "vascular permeability therapy" in cavernous angiomas?

PMID- 19404131
TI  - Endothelial progenitor cells in moyamoya disease.

PMID- 19404132
TI  - Stem cell populated implanted trachea.

PMID- 19404133
TI  - Choice of imaging for low-back pain: does it matter?

PMID- 19404134
TI  - Imaging cellular therapeutics: a novel approach.

PMID- 19404135
TI  - Targeted oncogenes create a new realistic mouse model of glioblastoma multiforme.

PMID- 19404137
TI  - A new era of outcomes research.

PMID- 19404136
TI  - "TOR"rific potential for new human therapies?

PMID- 19404141
TI  - Virtual neurosurgery: forceps, scissors, and suction meet the microprocessor,
      rocket science, and nuclear physics.

PMID- 19404142
TI  - Consensus statement on concussion in sport--the 3rd International Conference on
      Concussion, Zurich, November 2008.

PMID- 19404143
TI  - The metamorphosis of neurological surgery and the reinvention of the
      neurosurgeon.
AB  - Since its inception more than 12,000 years ago, neurosurgery has progressed
      through a number of phases, largely dictated by the available supporting bodies
      of information and technical adjuvants that allowed progress. The recent rapid
      escalation of technical progress related to surgery of the nervous system as well
      as global and regional climates have created diverse demands for the field and
      have challenged traditional methods of education for developing needed
      neurosurgical expertise. The creation of the "new neurosurgeon" is, in fact, the
      creation of many individuals and is dependent on objectives that are based on the
      needs directed toward the field. These needs are local, national, and
      international, and they are created by medical, scientific, economic, social, and
      political factors. Specific education should be directed toward these needs from
      early educational involvements at the premedical level but also should pervade
      the entire medical specialty exposure and postgraduate training. This
      communication discusses specific categories of needs and makes suggestions
      regarding programs and involvements that may address elements of the situation.
      General information and educational principles are discussed, along with
      recommendations for the fostering of a climate of innovation for the field.

PMID- 19404144
TI  - Optogenetic neuromodulation.
AB  - Modulation of the nervous system by electrical or chemical means
      (neuromodulation) is becoming increasingly sophisticated, with application to a
      growing number of neurological diseases. However, both chemical and electrical
      neuromodulation are limited in their specificity. Electrical stimulation, for
      example, indiscriminately activates different neuronal populations within the
      electrical field, leading to side effects that can limit efficacy. The delivery
      of genes that encode proteins capable of conveying light sensitivity to neurons
      has provided a tool that may overcome some of the limitations of traditional
      neuromodulation techniques. Activation or inhibition of specific neuronal
      populations with different wavelengths of light opens up possibilities for
      modulating neural circuits with previously unimagined levels of precision. We
      briefly review this new technology, illustrating its advantages and potential
      applications.

PMID- 19404145
TI  - Surrogate markers predict angiogenic potential and survival in patients with
      glioblastoma multiforme.
AB  - OBJECTIVE: The neovascularization of malignant brain tumors is a poorly
      understood phenomenon. Radiographic and histological evidence of increased
      vascularity correlate with clinical grade of gliomas. However, a quantitative
      noninvasive assay to assess glioma vascularity and associated clinical
      aggressiveness has not been developed. Circulating endothelial progenitor cells
      are unique vascular precursors recruited from the bone marrow through the
      circulation to form new tumor blood vessels. These cells were measured in
      patients undergoing surgery for glioblastoma multiforme (GBM). We hypothesized
      that this might reflect the extent of tumor vascularity, predict prognosis, or be
      useful as an assay to assess response to antiangiogenesis therapies. In addition,
      we report on a novel in vitro assay to assess the proangiogenic activity within
      the plasma samples obtained from glioma patients. METHODS: Fifty-six patients
      with various-grade gliomas had peripheral venous blood collected at the time of
      surgery and at subsequent visits during the follow-up period. The blood was
      separated into plasma and cellular fractions. The plasma was utilized in a human
      umbilical vein endothelial cell-based angiogenic assay. The cellular fraction
      containing endothelial progenitor cells was isolated, and specific cellular
      phenotypes were immunologically separated and counted using flow cytometry.
      Pathological samples were reviewed at the time of initial resection, and each
      patient's clinical course was monitored until the time of manuscript submission.
      RESULTS: Plasma derived from peripheral blood of patients with GBM scored
      significantly higher on the functional angiogenic scale compared with plasma
      derived from patients with low-grade gliomas and from controls. In addition, all
      patients with GBM had measurable numbers of bone marrow-derived endothelial
      precursor cells coexpressing CD133 and vascular endothelial growth factor
      receptor 2 in their peripheral circulation at the time of tumor resection. These
      cells range from less than 0.1% to 1.6% of the entire circulating mononuclear
      white blood cell population, or approximately 200,000 cells in some patients. A
      statistically significant relationship was observed between the percentage of
      endothelial progenitor cells in the peripheral blood at the time of initial GBM
      resection and survival. CONCLUSION: These studies suggest that plasma and
      circulating CD133+ vascular endothelial growth factor receptor 2+ proangiogenic
      cells are present in the peripheral blood of patients with glioma and can be used
      as a surrogate biomarker to measure tumor angiogenicity. These cells can be
      measured at the time of diagnosis and monitored in the postoperative period.
      These assays can be used to predict tumor aggressiveness. Also promising is their
      potential to identify patients with increased angiogenic activity who might
      respond maximally to antiangiogenesis therapies or to assess tumor response in
      patients using those therapies as the use of these adjuvant molecular modalities
      becomes more prevalent in neuro-oncology.

PMID- 19404146
TI  - The survival impact of postoperative infection in patients with glioblastoma
      multiforme.
AB  - OBJECTIVE: The capacity for local infection to prolong survival in patients with
      cancer is a widely accepted but unsubstantiated principle. The neurosurgical
      literature contains anecdotal reports of patients with malignant gliomas who
      experienced prolonged remission of their tumors after a bacterial infection. This
      association has not been explored in a larger series of patients with malignant
      glioma with postoperative infections. METHODS: A single-center operative
      experience accumulated over 10 years was examined to evaluate whether
      postoperative infections conferred a survival advantage in patients with
      glioblastoma multiforme. A total of 382 patients were examined, and 18 bacterial
      infections were identified. The vast majority (17 cases, 94%) of these were gram
      positive infections. Cases were compared with age-matched controls. Survival
      differences were evaluated using Kaplan-Meier curves, and other differences were
      tested using the Mann-Whitney U test. RESULTS: Cases and controls were younger
      and survived longer than the overall study sample, but cases and controls were
      similar at baseline. A moderate, statistically insignificant survival advantage
      was seen in the case group (Kaplan-Meier P = 0.27). However, when patients with
      infections in the first quarter and first half of their postoperative survival
      were examined, this survival advantage disappeared. There was no significant
      survival difference in any subgroup analyzed, including deep infections, bone
      flap infections, or infections caused by any specific organism. CONCLUSION: In
      this single-center study, postoperative infection did not confer any survival
      advantage in patients with glioblastoma multiforme.

PMID- 19404147
TI  - Awake craniotomy for brain tumors near eloquent cortex: correlation of
      intraoperative cortical mapping with neurological outcomes in 309 consecutive
      patients.
AB  - OBJECTIVE: Intraoperative localization of cortical areas for motor and language
      function has been advocated to minimize postoperative neurological deficits. We
      report herein the results of a retrospective study of cortical mapping and
      subsequent clinical outcomes in a large series of patients. METHODS: Patients
      with intracerebral tumors near and/or within eloquent cortices (n = 309) were
      clinically evaluated before surgery, immediately after, and 1 month and 3 months
      after surgery. Craniotomy was tailored to encompass tumor plus adjacent areas
      presumed to contain eloquent cortex. Intraoperative cortical stimulation for
      language, motor, and/or sensory function was performed in all patients to safely
      maximize surgical resection. RESULTS: A gross total resection (> or =95%) was
      obtained in 64%, and a resection of 85% or more was obtained in 77% of the
      procedures. Eloquent areas were identified in 65% of cases, and in that group,
      worsened neurological deficits were observed in 21% of patients, whereas only 9%
      with negative mapping sustained such deficits (P < 0.01). Intraoperative
      neurological deficits occurred in 64 patients (21%); of these, 25 (39%)
      experienced worsened neurological outcome at 1 month, whereas only 27 of 245
      patients (11%) without intraoperative changes had such outcomes (P < 0.001). At 1
      month, 83% overall showed improved or stable neurological status, whereas 17% had
      new or worse deficits; however, at 3 months, 7% of patients had a persistent
      neurological deficit. Extent of resection less than 95% also predicted worsening
      of neurological status (P < 0.025). CONCLUSION: Negative mapping of eloquent
      areas provides a safe margin for surgical resection with a low incidence of
      neurological deficits. However, identification of eloquent areas not only failed
      to eliminate but rather increased the risk of postoperative deficits, likely
      indicating close proximity of functional cortex to tumor.

PMID- 19404148
TI  - Neural connection between bilateral basal temporal regions: cortico-cortical
      evoked potential analysis in patients with temporal lobe epilepsy.
AB  - OBJECTIVE: In patients with temporal lobe epilepsy, invasive
      electroencephalographic study has shown that epileptic activities arising from
      the unilateral temporal lobe often propagate to the contralateral temporal lobe.
      Which commissural pathways are responsible for this spreading remains
      controversial. Some previous studies, however, have suggested that
      interhemispheric connections between bilateral basal temporal regions (BTR) might
      have a significant role in propagation of epileptic activities. METHODS: We
      attempted to elucidate the neural connections between bilateral BTRs using the
      cortico-cortical evoked potential (CCEP) method. Five consecutive patients with
      temporal lobe epilepsy who underwent intracranial electroencephalographic
      monitoring were studied. RESULTS: CCEP responses were recorded from a total of 24
      electrodes after stimulation of the contralateral BTRs (24 CCEPs/720 recordings;
      3.33%). There were 3 types of CCEP waveform: type N-P (16 of 24; 66.7%)
      consisting of an initial negative peak followed by a positive peak; type N (4 of
      24; 16.7%) showing a negative peak only, and type P (4 of 24; 16.7%) showing a
      positive peak only. The latencies ranged from 48.2 to 102.3 ms (mean, 65.5 ms)
      for negative peaks and 70.2 to 122.0 ms (mean, 95.2 ms) for positive peaks. In
      all patients, the basal temporal language area was associated with at least 1
      CCEP, either as a stimulated region or a recorded region (11 of 24; 45.8%).
      CONCLUSION: These data indicate that there is a neural connection between
      bilateral BTRs. In consideration of the involvement of the basal temporal
      language area, we speculate that these responses may reflect some physiological
      connections between bilateral BTRs.

PMID- 19404149
TI  - Influence of motor functional magnetic resonance imaging on the surgical
      management of children and adolescents with symptomatic focal epilepsy.
AB  - OBJECTIVE: To determine the clinical value of motor functional magnetic resonance
      imaging (fMRI) in the presurgical evaluation of a large group of children and
      adolescents with epilepsy caused by lesions close to the central sulcus. METHODS:
      Forty-three patients (19 males; mean age, 13 years) with lesional focal epilepsy
      underwent motor fMRI as part of a multidisciplinary standardized presurgical
      evaluation between 2000 and 2006. fMRI data were analyzed using statistical
      parametric mapping (SPM2) and screened for the presence of movement-related
      artifacts. The ways in which the results of motor fMRI influenced the decision
      making process were reviewed. RESULTS: The success rate of motor fMRI was 93% and
      data were of high quality in 67.5% of the patients. Together with other clinical
      considerations, motor fMRI results contributed to the surgical management of 32
      patients (74%). They helped 1) to determine the type of surgery in 23 patients
      (72%; 12 cases with and 11 cases without invasive functional mapping), 2) to
      indicate a reduced benefit-risk ratio with the consequence that surgery was not
      further considered in 5 patients (16%), and 3) to indicate that surgery was not
      an appropriate option because of the high risk of motor function deficit in 4
      patients (12%). CONCLUSION: Motor fMRI can be performed with a high degree of
      success and good data quality in this population of patients. It has an important
      additive role in the discussion of the feasibility of resective surgery
      contributing to the decision-making process for children with epilepsy caused by
      brain lesions close to the central sulcus.

PMID- 19404151
TI  - Radionuclide shunt patency study for evaluation of suspected ventriculoperitoneal
      shunt malfunction in adults with normal pressure hydrocephalus.
AB  - OBJECTIVE: Shunt patency studies are performed to determine whether shunt
      revision surgery is needed in malfunctioned ventriculoperitoneal shunt. The aim
      of our study was to develop a simple diagnostic algorithm in the diagnostic
      workup and identify factors associated with improvement after revision surgery.
      METHODS: A retrospective review of patients with confirmed shunt obstruction who
      underwent a revision surgery and were followed for 6 to 12 months was performed.
      A simpler algorithm to identify shunt obstruction was created and compared with
      the 4-variable algorithm. RESULTS: Of the 63 patients in whom shunt obstruction
      was suspected, 39 were diagnosed with complete or partial obstruction. Thirty
      seven patients underwent shunt revision surgery that included removal of shunt (n
      = 2), conversion to a ventriculoatrial shunt (n = 8), and relocation of the
      distal end of the catheter into a different part of the peritoneal cavity (n =
      27). Improvements were seen in 63.3% (n = 19) of patients evaluated at 6 months
      and 63.6% (n = 14) of patients evaluated at 12 months. The positive predictive
      value of the study was 80%. A simpler 1-variable algorithm using T(1/2) (half
      time) could correctly classify 86.9% of patients with shunt obstruction, compared
      with a 4-variable algorithm that correctly classified 80% of patients.
      CONCLUSION: Shunt patency studies are very useful for evaluation of shunt
      patency. Their results can be interpreted using a single-variable (T(1/2))
      algorithm. Patients most likely to respond to a revision surgery are those who
      had a good response to original placement of a ventriculoperitoneal shunt.

PMID- 19404152
TI  - Cerebrospinal fluid drainage and dynamics in the diagnosis of normal pressure
      hydrocephalus.
AB  - INTRODUCTION: Because of the difficulty in distinguishing idiopathic normal
      pressure hydrocephalus (INPH) from other neurodegenerative conditions unrelated
      to cerebrospinal fluid (CSF) dynamics, response to CSF shunting remains highly
      variable. We examined the utility of CSF drainage and CSF pressure (Pcsf)
      dynamics in predicting response to CSF shunting for patients with INPH. METHODS:
      Fifty-one consecutive INPH patients underwent continuous lumbar Pcsf monitoring
      for 48 hours followed by 72 hours of slow CSF drainage before
      ventriculoperitoneal shunting. Response to CSF drainage and B-wave
      characteristics were assessed via multivariate proportional-hazards regression
      analysis. RESULTS: Improvement in 1, 2, or all 3 INPH symptoms was observed in 35
      (69%), 28 (55%), and 11 (22%) patients, respectively, after CSF shunt
      implantation by 12 months after surgery. A positive response to CSF drainage was
      found to be an independent predictor of shunt responsiveness (relative risk,
      0.30; 95% confidence interval, 0.09-0.98; P = 0.05). There was no difference in
      Pcsf wave characteristics between the shunt-responsive and -nonresponsive groups,
      regardless of whether 1-, 2-, or 3-symptom improvement was used to define
      response to CSF shunting. CONCLUSION: In this study of 51 INPH patients who
      underwent Pcsf monitoring with waveform analysis and CSF drainage followed by
      shunt surgery, there was no correlation between specific Pcsf wave
      characteristics and objective symptomatic improvement after shunt placement. Pcsf
      monitoring with B-wave analysis contributes little to the diagnostic dilemma with
      INPH patients. Clinical response to continuous CSF drainage over a 72-hour period
      suggests a high likelihood of shunt responsiveness.

PMID- 19404154
TI  - Remnants of occipital vertebrae: proatlas segmentation abnormalities.
AB  - OBJECTIVE: Developmental remnants around the foramen magnum, or proatlas
      segmentation abnormalities, have been recorded in postmortem studies but very
      rarely in a clinical setting. Because of their rarity, the pathological anatomy
      has been misunderstood, and treatment has been fraught with failures. The
      objectives of this prospective study were to understand the correlative anatomy,
      pathology, and embryology and to recognize the clinical presentation and gain
      insights on the treatment and management. METHODS: Our craniovertebral junction
      (CVJ) database started in 1977 and comprises 5200 cases. This prospective study
      has retrieval capabilities. Neurodiagnostic studies changed with the evolution of
      imaging. Seventy-two patients were recognized as having symptomatic proatlas
      segmentation abnormalities. RESULTS: Ventral bony masses from the clivus or
      medial occipital condyle occurred in 66% (44/72), lateral or anterolateral
      compressive masses in 37% (27 of 72 patients), and dorsal bony compression in 17%
      (12 of 72 patients). Hindbrain herniation was associated in 33%. The age at
      presentation was 3 to 23 years. Motor symptoms occurred in 72% (52 of 72
      patients); palsies in Cranial Nerves IX, X, and XII in 33% (24 of 72 patients);
      and vertebrobasilar symptoms in 25% (18 of 72 patients). Trauma precipitated
      symptoms in 55% (40 of 72 patients). The best definition of the abnormality was
      demonstrated by 3-dimensional computed tomography combined with magnetic
      resonance imaging. Treatment was aimed at decompression of the pathology and
      stabilization. CONCLUSION: Remnants of the occipital vertebrae around the foramen
      magnum were recognized in 72 of 5200 CVJ cases (7.2%). Magnetic resonance imaging
      with 3-dimensional computed tomography of the CVJ provides the best definition
      and understanding of the lesions. Brainstem myelopathy and lower cranial nerve
      deficits are common clinical presentations in the first and second decades of
      life. Treatment is aimed at decompression of the pathology and CVJ stabilization.

PMID- 19404153
TI  - Surgical treatment of cerebellar schistosomiasis.
AB  - OBJECTIVE: To explore the surgical treatment of cerebellar schistosomiasis.
      METHODS: Twelve cases of cerebellar schistosomiasis treated in our department
      were analyzed retrospectively. RESULTS: All cases were cured. At the 2-year
      follow-up examination, all patients could perform physical tasks normally.
      CONCLUSION: Cerebellar schistosomiasis tends to cause mass effect of the
      posterior cranial fossa and increased intracranial pressure. Microresection of
      the pathological focus and decompression of the posterior cranial fossa should be
      effective therapeutic measures.

PMID- 19404155
TI  - Radiographic restoration of lumbar alignment after transforaminal lumbar
      interbody fusion.
AB  - OBJECTIVE: Restoration of lumbar lordosis is a critical factor in long-term
      success after lumbar fusions. Transforaminal lumbar interbody fusion (TLIF) is a
      popular surgical technique in the lumbar spine, but few data exist on change in
      spinal alignment after the procedure. METHODS: Eighty patients who underwent TLIF
      surgery were retrospectively reviewed (minimum follow-up period, 2 years).
      Standing x-rays were assessed for changes in focal and segmental kyphosis, and
      restoration of lumbar lordosis. Improvement in spondylolisthesis, sagittal
      balance, and scoliosis were also assessed. Fusion was assessed as well. RESULTS:
      Eighty operations were performed at 107 levels. Mean presenting lumbar Cobb angle
      measurement (L1-S1) was 36.3 +/- 4.5 degrees (range, 12-77 degrees). Forty
      patients (50%) had sagittal imbalance. Mean postoperative Cobb angle (L1-S1) was
      55.1 +/- 6.6. Thirty-three of 36 patients with segmental kyphosis (92%) had
      restoration of lordosis. Improvement in alignment was most prominent at the
      surgical level (mean increase in lordosis, 20.2 +/- 4.2 degrees). The improvement
      in lumbar lordosis among patients undergoing multilevel TLIFs (27.3 +/- 3.4
      degrees) was significantly higher compared with patients undergoing single-level
      operations (17.4 +/- 4.4) (Student's t test, P = 0.0004). Thirty of the 40
      patients with sagittal imbalance (75%) achieved immediate restoration of normal
      sagittal balance. The ability to restore normal sagittal balance was correlated
      with a sagittal imbalance of less than 10 cm (P = 0.0001). Spondylolisthesis was
      completely corrected at the TLIF site in 90 of 99 levels (91%). Three patients
      (4%) required reoperation, 2 for implant disengagement and 1 for worsening
      kyphoscoliosis above the original surgical levels. Two of the 80 patients had
      pseudoarthrosis; hence, the rate of pseudoarthrosis was 2.5%. CONCLUSION: The
      TLIF operation is highly effective in improving spinal alignment in patients with
      degenerative spinal disorders when the appropriate surgical technique is
      implemented.

PMID- 19404157
TI  - Local chronic hypoperfusion secondary to sinus high pressure seems to be mainly
      responsible for the formation of intracranial dural arteriovenous fistula.
AB  - OBJECTIVE: To investigate the cause of intracranial dural arteriovenous fistula,
      focusing on the role of angiogenic factors and local chronic brain hypoperfusion.
      METHODS: One hundred twenty rats were assigned to 4 groups: group A (n = 35), the
      venous hypertension group; group B (n = 35), the venous hypertension and sinus
      thrombosis group; group C (n = 25), the sham operation group; and group D (n =
      25), the sagittal sinus thrombosis group. Mean arterial pressure, sinus pressure,
      cerebral perfusion pressure, and regional cerebral blood flow were monitored
      during the operation and 1, 2, 4, and 12 weeks after the operation.
      Immunohistological and Western blot analyses of vascular endothelial growth
      factor and matrix metalloproteinase-9 were performed, and perfusion magnetic
      resonance imaging of the brain was performed during the follow-up. RESULTS: In
      groups A and B, a decreased cerebral perfusion pressure from 98.25 +/- 5.83 to
      69.35 +/- 6.87 mm Hg and from 99.32 +/- 4.19 to 64.79 +/- 6.71 mm Hg was
      detected, respectively. Concurrently, the cerebral blood flow obviously
      decreased. In the right occipital lobe only, the hypoperfusion state lasted for
      12 weeks. Immunohistological staining of vascular endothelial growth factor was
      persistently positive in the right occipital lobe, arachnoid membrane, and nearby
      dura mater. Angiogenesis in the dura mater was prominent 12 weeks after the
      operation in groups A and B. Western blotting showed high expression of vascular
      endothelial growth factor and matrix metalloproteinase-9 in the dura mater in
      groups A and B. CONCLUSION: Chronic local hypoperfusion secondary to intracranial
      sinus high pressure seemed to be the main cause of angiogenesis in the dura
      mater, leading to the formation of intracranial dural arteriovenous fistula.

PMID- 19404156
TI  - In vitro characterization of a targeted, dye-loaded nanodevice for intraoperative
      tumor delineation.
AB  - OBJECTIVE: To synthesize and complete in vitro characterization of a novel, tumor
      targeted nanodevice for visible intraoperative delineation of brain tumors.
      METHODS: The ability of dye-loaded polyacrylamide nanoparticles (NP) containing
      methylene blue, Coomassie blue, or indocyanine green to cause color change in the
      9L glioma cell lines was evaluated. Cells were incubated with dye-loaded NPs,
      photographed, and analyzed colorimetrically. Confocal microscopy was used to
      determine subcellular localization of NPs in treated cells. RESULTS: Incubation
      of glioma cell lines with dye-loaded NPs resulted in clearly visible,
      quantifiable cell tagging in a dose- and time-dependent manner. Dye-loaded NPs
      were observed to bind to the surface and become internalized by glioma cells.
      Coating the NP surface with F3, a peptide that binds to the tumor cell surface
      receptor nucleolin, significantly increased NP affinity for glioma cells. F3
      targeting also significantly increased the rate of cell tagging by dye-loaded
      NPs. Finally, F3-targeted NPs demonstrated specificity for targeting various
      cancer cell lines based on their surface expression of cell surface nucleolin.
      CONCLUSION: F3-targeted dye-loaded NPs efficiently cause definitive color change
      in glioma cells. This report represents the first use of targeted NPs to cause a
      visible color change in tumor cell lines. Similar nanodevices may be used in the
      future to enable visible intraoperative tumor delineation during tumor resection.

PMID- 19404158
TI  - Intravenous polyethylene glycol successfully treats severe acceleration-induced
      brain injury in rats as assessed by magnetic resonance imaging.
AB  - OBJECTIVE: Polyethylene glycol (PEG) is a nontoxic molecule with known efficacy
      as a cell membrane sealant, improving histological and behavioral outcomes in
      trauma models. Diffusion-weighted (DW) magnetic resonance imaging (MRI) is the
      most sensitive method of detecting in vivo diffuse axonal injury (DAI), where a
      decreased apparent diffusion coefficient (ADC) of water reflects cytotoxic edema.
      We use DW-MRI to assess severe DAI in rats treated with a single acute postinjury
      injection of PEG. METHODS: Rats were divided into uninjured, injured saline
      treated, and injured PEG-treated groups. Injury groups received a severe brain
      injury using an impact-acceleration weight-drop model. Saline or PEG was
      administered acutely as a single intravenous dose to injured saline-treated and
      injured PEG-treated groups, respectively. DW-MRI analysis was performed at
      postinjury day 7 with a 9.4-T magnet. ADC was calculated for cortex, corpus
      callosum/hippocampus, and thalamus in each group. RESULTS: An expected decrease
      in ADC, representing cytotoxic edema, was observed in the injured saline-treated
      group. The injured PEG-treated group demonstrated no decrease in ADC relative to
      the uninjured rats, and the difference between ADC in saline and PEG-treated
      groups reached significance for all 3 zones of assessed brain. Differences were
      seen grossly between injured saline-treated and injured PEG-treated groups on
      representative color-mapped ADC images. CONCLUSION: A single intravenous dose of
      PEG dramatically limits sequelae of severe acceleration-induced brain injury--in
      this case, assessed by cytotoxic edema on DW-MRI--by intervening at the primary
      injury level of neuronal membrane disruption. This outcome is unprecedented, as
      no prior treatments for DAI have demonstrated similar efficacy. DAI treatment
      with intravenous PEG may have future clinical relevance and warrants further
      investigation.

PMID- 19404159
TI  - Transplanted bone marrow stromal cells promote axonal regeneration and improve
      motor function in a rat spinal cord injury model.
AB  - OBJECTIVE: Recent studies have indicated that bone marrow stromal cells (BMSCs)
      have the potential to improve neurological function when transplanted into animal
      models of spinal cord injury (SCI). However, it is still unclear how the
      transplanted BMSCs promote functional recovery after SCI. In this study,
      therefore, we evaluated how the transplanted BMSCs restore the function of the
      dorsal corticospinal tracts in the injured spinal cord. METHODS: The rats were
      subjected to incomplete SCI by means of a pneumatic impact device. BMSC or
      vehicle transplantation into the rostral site of SCI was performed at 7 days
      after injury. Neurological symptoms were assessed throughout the experiments.
      Fluoro-Ruby was injected into the dorsal funiculus of the rostral site of SCI at
      63 days after injury. The fate of the transplanted BMSCs was examined using
      immunohistochemistry. RESULTS: BMSC transplantation significantly enhanced
      functional recovery of the hind limbs. The number of Fluoro-Ruby-labeled fibers
      of the dorsal corticospinal tracts at the caudal site of SCI was significantly
      higher in the BMSC-transplanted animals than in the vehicle-transplanted animals.
      Some of the engrafted BMSCs were positive for Fluoro-Ruby, NeuN, and MAP2 in the
      gray matter, suggesting that they acquired neuronal phenotypes and built synaptic
      connection with the host's neural circuits. Others in the white matter
      morphologically simulated the astrocytes and were also positive for glial
      fibrillary acidic protein. CONCLUSION: The findings suggest that the transplanted
      BMSCs acquire neural cell phenotypes around the injury site and contribute to
      rebuild the neural circuits, including the corticospinal tract, promoting
      functional recovery of the hind limbs.

PMID- 19404160
TI  - Theodor Kocher's craniometer.
AB  - The first half of the 20th century witnessed the rapid emergence of neurological
      surgery as a surgical subspecialty. Only few surgeons made a name for themselves
      equally in general surgery and neurological surgery. One of them was the Swiss
      surgeon Theodor Kocher (1841-1917). He was honored with the Nobel Prize for his
      innovative approaches to pathology and surgery of the thyroid gland. Kocher also
      attracted students from all over the world to his laboratory to study the
      pathology of neurotrauma and the consequences of increased intracranial pressure
      on brain function. One of his most interesting contributions to the neurosurgical
      equipment of his time is a craniometer, used to correlate the location of
      intracranial pathology to landmarks on the surface of the cranium. Craniometers
      can be seen as simple forerunners of today's sophisticated stereotactic frames.
      They contributed significantly to the advancement of neurological surgery,
      allowing localization of known functional centers as well as lesions of the brain
      in a 3-dimensional system.

PMID- 19404161
TI  - Assessment between phosphoglycerate dehydrogenase gene and schizophrenia in
      Korean population.

PMID- 19404162
TI  - No association between Rho-associated coiled-coil forming protein
      serine/threonine kinase1 gene and schizophrenia in the Japanese population.

PMID- 19404163
TI  - Lack of association between polymorphisms of neuropeptide Y and schizophrenia in
      Korean population.

PMID- 19404150
TI  - Perioperative fever and outcome in surgical patients with aneurysmal subarachnoid
      hemorrhage.
AB  - OBJECTIVE: We examined the incidence of perioperative fever and its relationship
      to outcome among patients enrolled in the Intraoperative Hypothermia for Aneurysm
      Surgery Trial. METHODS: One thousand patients with initial World Federation of
      Neurological Surgeons grades of I to III undergoing clipping of intracranial
      aneurysms after subarachnoid hemorrhage were randomized to intraoperative
      normothermia (36 degrees C-37 degrees C) or hypothermia (32.5 degrees C-33.5
      degrees C). Fever (> or =38.5 degrees C) and other complications (including
      infections) occurring between admission and discharge (or death) were recorded.
      Functional and neuropsychologic outcomes were assessed 3 months postoperatively.
      The primary outcome variable for the trial was dichotomized Glasgow Outcome Scale
      (good outcome versus all others). RESULTS: Fever was reported in 41% of patients.
      In 97% of these, fever occurred in the postoperative period. The median time from
      surgery to first fever was 3 days. All measures of outcome were worse in patients
      who developed fever, even in those without infections or who were World
      Federation of Neurological Surgeons grade I. Logistic regression analyses were
      performed to adjust for differences in preoperative factors (e.g., age, Fisher
      grade, initial neurological status). This demonstrated that fever continued to be
      significantly associated with most outcome measures, even when infection was
      added to the model. An alternative stepwise model selection process including all
      fever-related measures from the preoperative and intraoperative period (e.g.,
      hydrocephalus, duration of surgery, intraoperative blood loss) resulted in the
      loss of significance for dichotomized Glasgow Outcome Scale, but significant
      associations between fever and several other outcome measures remained. After
      adding postoperative delayed ischemic neurological deficits to the model, only
      worsened National Institutes of Health Stroke Scale score, Barthel Activities of
      Daily Living index, and discharge destination (home versus other) remained
      independently associated with fever. CONCLUSION: These findings suggest that
      fever is associated with worsened outcome in surgical subarachnoid hemorrhage
      patients, although, because the association between fever and the primary outcome
      measure for the trial is dependent on the covariates used in the analysis
      (particularly operative events and delayed ischemic neurological deficits), we
      cannot rule out the possibility that fever is a marker for other events. Only a
      formal trial of fever treatment or prevention can address this issue.

PMID- 19404164
TI  - Functional and radiological outcomes of 360 degrees fusion of three or more
      motion levels in the lumbar spine for degenerative disc disease.
AB  - STUDY DESIGN: This is a single-center, multisurgeon, retrospective study of
      radiologic and functional outcome measures at a minimum 2-year follow-up.
      OBJECTIVE: We studied the radiologic and functional outcomes following 3 or more
      motion segment fusions of the lumbar spine for low back pain due to multilevel
      degenerative disc disease. SUMMARY OF BACKGROUND DATA: Good functional outcomes
      have been reported for 1 or 2-level fusions, but there are no reports dealing
      specifically with 3 or more level fusions. METHODS: A total of 80 adult patients
      met the inclusion/exclusion criteria of multilevel (3 or more motion segments)
      360 degrees fusion for lumbar degenerative disc disease, failed nonoperative
      treatment for at least 1 year, no previous lumbar fusion, no fracture, tumor or
      infection of the spine, completed preoperative and postoperative functional
      questionnaires including SF-36 (n = 80), Oswestry (n = 69), Roland Morris (n =
      68), and radiologic evaluation of fusion solidity with a minimum follow-up of 2
      years. RESULTS: The average patient age was 57 years (range, 27-81). The mean
      follow-up was 4 years (2-7). On average, patients had fusion of 4 motion segments
      (range, 3-8 levels). Solid arthrodesis at the first surgery was achieved in 65/80
      (81%). Adjacent segment degeneration was noted in 11 patients. Of these, 5 had
      undergone an extension of their fusion within the study period. There were no
      deaths or neurologic complications. Deep wound infection occurred in 2 patients,
      neither requiring implant removal. The Oswestry Disability Index scores improved
      from 49.8 to 35.1 (29.5%) (P < 0.001). The Roland Morris scores improved from
      17.6 to 12.2 (30.7%) (P < 0.001). For the SF-36 scales, significant (P < 0.001)
      improvement was seen in all scales except Role Emotional scores and Mental
      Composite Scales. CONCLUSION: The surgical treatment of lumbar degenerative disc
      disease by 360 degrees fusion should be considered for properly selected
      patients. The goal of surgery is reduction, not elimination of disability.

PMID- 19404165
TI  - Acute chest pain in a top soccer player due to thoracic disc herniation.
AB  - STUDY DESIGN: Case report. OBJECTIVE: An unusual and previously not reported case
      of upper thoracic disc herniation combined with acute chest pain, is presented.
      SUMMARY OF BACKGROUND DATA: Disc herniation in the thoracic spine is rare. There
      are only a few cases of thoracic disc herniation in top athletes presented in the
      literature. The clinical presentation of a thoracic disc herniation can vary
      widely depending on its location and morphologic characteristics. Clinically, the
      acute symptoms may be severe. METHODS: A 24-year-old soccer player with acute
      left-sided chest pain that started in the middle of a soccer game has been
      followed clinically and with MRI examinations for 3 years. RESULTS: MRI of the
      thoracic spine showed a left-sided paramedial disc herniation at T2-T3 level and
      the right-sided paramedial disc herniation at T3-T4 level. The player was
      prescribed initial rest and subsequent physical rehabilitation. He had no further
      symptoms during rehabilitation to full training, and could resume play and
      remained symptom free for the rest of the season.The following season, the player
      experienced a similar sudden thoracic pain episode during training. This time the
      chest pain was right-sided. A new MRI of the thoracic spine showed unchanged
      findings. The initial rehabilitation was similar to the one used in the first
      episode. After 15 months with no symptoms during normal life the player was
      allowed to increase the intensity of training gradually and after 2 years the
      patient played soccer at elite level again. However, 3 years later the symptoms
      relapsed and the player ended his career after another rehabilitation period.
      CONCLUSION: In conclusion, it is important to consider thoracic disc herniation
      as acute chest pain in athletes and that the long-term prognosis of this entity
      is not always good.

PMID- 19404166
TI  - Dumbbell synovial sarcoma of the thoracolumbar spine: a case report.
AB  - STUDY DESIGN: A case report is of a giant dumbbell-shaped synovial sarcoma of the
      thoracolumbar spine is presented. OBJECTIVE: To report a case of a rare dumbbell
      shaped tumor treated by multimodal approach. Surgical procedures, adjuvant
      treatment, and outcome were discussed. SUMMARY OF BACKGROUND DATA: Synovial
      sarcomas of the spine are very rare tumors. Radical surgical resection is the
      goal, but is often not feasible. Dumbbell-shaped spinal synovial sarcoma with a
      giant extraspinal extension has not yet been reported. The rationale for 2-step
      surgical procedure and adjuvant therapy is discussed in light of the clinical
      picture, preoperative imaging and extension of the disease. METHODS: A 32-year
      old male patient presented with signs of quickly progressive paraparesis. A
      dumbbell-shaped tumor at the level Th12-L1 was found with a giant retroperitoneal
      extension. Tumor was nonradically excised in a 2-step operation: first through a
      dorsal approach with laminectomy and removal of the intraspinal extradural part,
      and later through a laparotomy with removal of the retroperitoneal part.
      Histologic examination revealed highly malignant synovial sarcoma. Patient was
      treated with chemotherapy and radiotherapy after surgery. RESULTS: Patient was in
      remission and symptom free for 1 year after surgery; he then developed a local
      recurrence and died soon afterwards. CONCLUSION: A good treatment result was
      achieved initially. A combined approach in cases like this is warranted, with as
      radical surgery as possible in order to avoid local recurrence, a common cause of
      treatment failure in sarcomas.

PMID- 19404167
TI  - Myositis ossificans in psoas muscle after lumbar spine fracture.
AB  - STUDY DESIGN: A case report. OBJECTIVE: To report a case of myositis ossificans
      in the psoas muscle after lumbar spine fracture. SUMMARY OF BACKGROUND DATA:
      Myositis ossificans is a benign condition of heterotopic bone formation in
      skeletal muscle. It predominantly occurs in large muscles of extremities
      following injury. Occurrence in the psoas muscle is rare with no previous reports
      of this condition associated with vertebral fracture in patients without
      hematologic abnormality. METHODS: A 56-year-old man was referred to our hospital
      for a mass located in the left psoas muscle and an L3 compression fracture. He
      complained of low back and left leg pain after a fall 2 weeks previously.
      Magnetic resonance (MR) imaging obtained 12 days after trauma showed an L3
      compression fracture with a left psoas mass with low T1 and high T2 signal
      intensity, associated edema, and enhancement. Computed tomography (CT) scans
      showed a suspicious slightly high-density mass in the left psoas area. The
      radiologic features of the mass were consistent with a hematoma. RESULTS: After 1
      week, CT scans showed calcification at the hematoma site. Histologic examination
      following CT-guided biopsy demonstrated new bone formation, atrophy of skeletal
      muscle fibers, and fibrosis. Lymphocytes were focally infiltrating. Irregularly
      anastomosing bony trabeculae and fibroblastic cell proliferation were noted. On
      follow-up MRI and CT scans 2 months later, the previous calcified mass was no
      longer evident. CONCLUSION: Myositis ossificans usually occurs in extremities and
      is very uncommon in the psoas muscle. We report psoas myositis ossificans that
      developed from hemorrhage and edema associated with a lumbar fracture and
      required only 2 months to regress completely. When one finds a soft tissue mass
      with surrounding edema in the psoas muscle combined with a vertebral compression
      fracture, myositis ossificans should be included in the differential diagnosis.

PMID- 19404168
TI  - Bilateral pneumothoraces, pneumomediastinum, pneumoperitoneum,
      pneumoretroperitoneum, and subcutaneous emphysema after thoracoscopic anterior
      fracture stabilization.
AB  - STUDY DESIGN: Case report and clinical discussion. OBJECTIVE: A rare case of air
      passage into multiple body compartments after thoracoscopic minimally invasive
      spine surgery is described. SUMMARY OF BACKGROUND DATA: In recent years, there is
      growing interest in thoracoscopic minimally invasive spine surgery for the
      treatment of thoracic and lumbar spine fractures. Severe complications due to the
      operative procedure are rare. METHODS: We present a case of a 73-year-old woman
      who developed bilateral pneumothoraces, pneumomediastinum, pneumoperitoneum,
      pneumoretroperitoneum, and subcutaneous emphysema after thoracoscopic anterior
      stabilization of a Th12 fracture. RESULTS: The operative procedure was completed
      without any obvious intraoperative complications. Routine made postoperative
      radiograph of the chest revealed a pneumothorax on the right side, bilateral
      subphrenic free air, and bilateral supraclavicular air. Subsequently, a CT scan
      showed bilateral pneumothoraces, pneumomediastinum, pneumoperitoneum,
      pneumoretroperitoneum and a supraclavicular subcutaneous emphysema. Bronchoscopy,
      esophagogastroduodenoscopy, and laryngoscopy showed no hollow organ injury or any
      other pathologic changes. Intraabdominal free air and pneumothoraces could not be
      detected on thoracic radiographs after 2 days. The patient remained
      cardiopulmonary stable throughout the hospital course. CONCLUSION: This report
      documents a rare case of air passage into multiple body compartments after
      thoracoscopic-assisted treatment of a spinal fracture, which has not yet been
      described previously. After exclusion of a tracheo-bronchial and hollow organ
      injury the process was self-limiting. To avoid this complication, special care
      should be taken to evacuate all intrathoracal air at the end of the endoscopic
      procedure.

PMID- 19404169
TI  - Paraplegia caused by an epidural hematoma in a patient with unrecognized chronic
      idiopathic thrombocytopenic purpura following an epidural steroid injection.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To report a rare case of complicated
      paraplegia caused by a spontaneous epidural hematoma following an epidural
      steroid injection in a patient with unrecognized chronic idiopathic
      thrombocytopenic purpura (ITP) and to review relevant literature and discuss
      etiology, pathogenesis, and clinical features. SUMMARY OF BACKGROUND DATA: A
      spinal epidural hematoma is a rare but potentially catastrophic complication,
      which could develop in patients without any risk factors. Some patients with
      chronic ITP are asymptomatic. To our knowledge there has been no previous report
      of such a complication. METHODS: This is a retrospective review of a case seen at
      our institution. RESULTS: The authors present a case of a 67-year-old woman who
      received an epidural steroid injection following complaints of lower back pain
      and bilateral buttock and leg pain. One day later, the patient had right leg
      numbness and weakness extending to her right knee; she was taken for emergency
      surgery. An emergency magnetic resonance imaging revealed an epidural hematoma
      with high-signal intensity on T2 imaging in the lumbar spinal cord and spinal
      cord compression with subdural hematoma. One week later, she was progressively
      developing lower extremity paraplegia with an L1 motor level and no sensory or
      sphincter activity. She was taken from the emergency room at our institution to
      the operating room for emergency decompression. After an uneventful course for 1
      year, the patient presented with progressive bilateral lower extremity paralysis.
      CONCLUSION: Epidural steroid therapy is a commonly used conservative therapy;
      however, complications could develop in patients without any risk factors.
      Clinicians who plan an epidural steroid injection must perform a rigorous
      evaluation through a detailed physical examination, simple laboratory tests, and
      history taking to prevent various risks associated with spinal cord compression.

PMID- 19404170
TI  - Stress fracture of bilateral posterior facet after insertion of interspinous
      implant.
AB  - STUDY DESIGN: A case report of stress fracture of bilateral lumbar posterior
      facet after implantation of interspinous process device is reported and the
      literature reviewed. OBJECTIVE.: To report the rare case of stress fracture of
      bilateral lumbar posterior facet after implantation of interspinous process
      device. SUMMARY OF BACKGROUND DATA: A 64-year-old woman presented with severe
      back pain and radiating pain in both legs. In her history, she had undergone
      implantation of L4-L5 interspinous process device (Coflex, Paradigm Spine,
      Wurmlingen, Germany) for her neurogenic claudication at 6 years ago. Magnetic
      resonance image demonstrated signal change suggesting bilateral L4 inferior
      process. To the best of the authors' knowledge, there has been no report stress
      fracture of posterior facet after implantation of interspinous process device.
      METHODS: This study reviewed the patient's medical record, her imaging studies,
      and related literatures. RESULTS: In the reported case, stress fracture of
      bilateral posterior facet was documented with MRI and confirmed with surgical
      treatment for the surgical treatment of spinal stenosis. The involved facet joint
      was at the site affected by previously implanted interspinous process device.
      CONCLUSION: Posterior facet fracture can occur as a complication of interspinous
      process device.

PMID- 19404172
TI  - Effectiveness of physical therapy and epidural steroid injections in lumbar
      spinal stenosis.
AB  - STUDY DESIGN: Randomized single-blind controlled trial. OBJECTIVE: We aimed to
      compare the effects of epidural steroid injections and physical therapy program
      on pain and function in patients with lumbar spinal stenosis (LSS). SUMMARY OF
      BACKGROUND DATA: LSS is one of the most common degenerative spinal disorders
      among elderly population. Initial treatment of this disabling painful condition
      is usually conservative including analgesics, nonsteroidal anti-inflammatory
      drugs, exercise, physical therapy, or epidural steroid injections. Owing to lack
      of sufficient data concerning the effectiveness of conservative treatment in LSS,
      we aimed to compare the effectiveness of epidural steroid injections and physical
      therapy program in a randomized controlled manner. METHODS: A total of 29
      patients diagnosed as LSS were randomized into 3 groups. Group 1 (n = 10)
      received an inpatient physical therapy program for 2 weeks, group 2 (n = 10)
      received epidural steroid injections, and group 3 (n = 9) served as the controls.
      All study patients additionally received diclofenac and a home-based exercise
      program. The patients were evaluated at baseline, 2 weeks, 1 month, 3 months, and
      6 months after treatment by finger floor distance, treadmill walk test, sit-to
      stand test, weight carrying test, Roland Morris Disability Index, and Nottingham
      Health Profile. RESULTS: Both epidural steroid and physical therapy groups have
      demonstrated significant improvement in pain and functional parameters and no
      significant difference was noted between the 2 treatment groups. Significant
      improvements were also noted in the control group. Pain and functional assessment
      scores (RMDI, NHP physical activity subscore) were significantly more improved in
      group 2 compared with controls at the second week. CONCLUSION: Epidural steroid
      injections and physical therapy both seem to be effective in LSS patients up to 6
      months of follow-up.

PMID- 19404174
TI  - Degenerative anular changes induced by puncture are associated with insufficiency
      of disc biomechanical function.
AB  - STUDY DESIGN: In vivo experiments to examine physiologic consequences and in
      vitro tests to determine immediate biomechanical effects of anular injury by
      needle puncture. OBJECTIVE: To determine whether a relationship exists between
      induction of degenerative changes in anulus fibrosus (AF) and compromised disc
      biomechanical function according to injury size. SUMMARY OF BACKGROUND DATA:
      Various studies in intervertebral disc mechanics, degeneration, and regeneration
      involve the creation of a defect in the anulus fibrosus (AF). However, the impact
      of the puncture, itself, on biomechanical function and disc health are not
      understood. METHODS: For in vivo experiments, rat caudal discs subjected to
      percutaneous anular punctures using different gauge size hypodermic needles (18,
      22, 26 g) and nonpunctured controls were examined histologically up to 4 weeks
      postsurgery. For in vitro biomechanical testing, healthy motion segments were
      isolated and their creep compression response assessed immediately after needle
      puncture. RESULTS: We found that needle size-dependence of creep compression
      behavior paralleled the size-dependence of degenerative changes in the AF.
      Specifically, 18-g punctures resulted in inward bulging of the AF, lamellar
      disorganization, and cellular changes. These changes were not seen in 22- and 26
      g punctured discs. Biomechanical tests showed that only 18-g needle punctures led
      to significant changes in disc mechanics. Importantly, a statistically
      significant association was found between needle sizes that caused biomechanical
      changes and induction of degenerative changes in the AF. CONCLUSION: Our findings
      suggest that injury sizes large enough to disrupt biomechanical function are
      needed to drive degenerative changes in rat caudal disc AF. Based on the data, we
      believe that small anular defects become sealed, allowing the disc to function
      normally and the AF to heal. Larger defects appear to require longer wound
      closure times, and may prolong the duration of impaired disc function.

PMID- 19404173
TI  - Vasomotion of intraradicular microvessels in rat.
AB  - STUDY DESIGN: This study is to investigate the changes of vasomotion of
      intraradicular microvessels in vivo. OBJECTIVE: We have observed microvascular
      corrosion casts of the lumbar nerve root by scanning electron microscopy and used
      an immunohistochemical technique to investigate the presence and distribution of
      autonomic and sensory nerve in blood vessels of the nerve root. SUMMARY OF
      BACKGROUND DATA: It is generally considered that the genesis of radiculopathy
      associated with the degenerative conditions of the spine may result from both
      mechanical compression and circulatory disturbance. However, the neurogenic
      control of intraradicular blood flow has received little attention in the past.
      METHODS: For three-dimensional observation of intraradicular vessels, we used
      scanning electron microscopic examination of microvascular corrosion casts in ten
      Wister rats. To investigate the mechanism of vasomotion of the nerve root, we
      used immunohistochemical methods. The sections were incubated overnight with
      antisera to tyrosine hydroxylase, choline acetyl transferase, substance P,
      calcitonin-gene-related peptide, vasoactive intestinal peptide, somatostatin,
      neuropeptide Y, leucine-enkephalin, cholecystokinin octapeptide, brain-nitric
      oxide synthase, and endothelium-nitric oxide synthase. Abidin-biotin complex
      method was used as the immunohistochemical procedure and the sections were
      observed under the light microscope. RESULTS: The general view of whole vascular
      casts of the lumbar spinal cord and nerve roots showed a high density of vessels.
      Bifurcation or anastomoses of capillaries approximately took place at right
      angles in a T-shaped pattern and capillaries showed a lot of ring-like
      compressions. This ring-like compression on the cast may represent a vascular
      sphincter in the microvessels. This study also reveals the existence of
      perivascular adrenergic, cholinergic, peptidergic, and nitroxydergic innervation
      with a possible role in neurogenic regulation of nerve root circulation.
      CONCLUSION: Perivascular nerve plexuses around intraradicular microvessels
      suggest that the autonomic nerves play an important role in intraradicular
      circulation.

PMID- 19404176
TI  - Effect of modified techniques in Bryan cervical disc arthroplasty.
AB  - STUDY DESIGN: A prospective, randomized study of the clinical and radiographic
      outcomes in patients undergoing single- and 2-level cervical arthroplasty with
      Bryan cervical disc (Medtronic Sofamor Danek, Memphis, TN). OBJECTIVE: This study
      was designed to investigate the modified techniques of cervical arthroplasty with
      Bryan disc and analyze the clinical and radiologic effects. SUMMARY OF BACKGROUND
      DATA: Aggravation of kyphosis is the known challenge after arthroplasty. Disc
      insertion angle and overmilling were reported to be factors causing kyphosis.
      However, few studies have performed methods to avoid these factors. Additionally,
      translation and length matching of prosthesis seemed to be ignored. There have
      been no studies regarding the effects of modified techniques for the prevention
      of these adverse outcomes. METHODS: Modified techniques include change in disc
      insertion, reducing overmilling of endplates, the assurance of the anterior
      borders at the same horizontal line, and the accurate fitness of prosthesis size.
      Techniques described in product monograph were applied to 20 patients (control
      group) and modified techniques were applied to 19 patients (investigational
      group). Clinical and radiologic (radiograph) follow-ups of all the patients were
      performed before surgery and after surgery (6 months). Comparisons between the 2
      groups in terms of functional spinal unit angle, shell angle, the anteroposterior
      displacement between the 2 metal shells in the neutral position, and the fitness
      of prosthesis size were performed. RESULTS: Radiologic outcomes in
      investigational group were significantly superior to those in control group;
      clinical outcomes were similar in both groups. CONCLUSION: The modified
      techniques can improve the outcomes of the cervical arthroplasty with Bryan disc
      and prevent the unexpected imbalance and motion of cervical spine.

PMID- 19404175
TI  - The mandibular angle as a landmark for identification of cervical spinal level.
AB  - STUDY DESIGN: Retrospective radiographic review. OBJECTIVE: To determine the
      utility of the mandibular angle as a landmark for identification of cervical
      spinal level. SUMMARY OF BACKGROUND DATA: Improper localization of the skin
      incision during anterior cervical spine surgery may lead to increased technical
      difficulty of the surgery. Although the use of traditional palpable anterior neck
      landmarks (hyoid bone, cricoid cartilage, thyroid cartilage, and carotid
      tubercle) help identify appropriate spinal levels, their reliability has not been
      validated in actual surgeries. We hypothesize that the angle of the mandible (AM)
      is a consistently palpable landmark, and that the mandible can be used to
      accurately template the distance to subaxial cervical levels using preoperative
      radiographs. METHODS: As a pilot study, we prospectively evaluated 30 consecutive
      patients who underwent anterior cervical diskectomy and fusion to assess the
      interobserver accuracy of palpating the mandibular angle, hyoid, carotid
      tubercle, and thyroid and cricoid cartilages. In a second set of 26 consecutive
      patients undergoing anterior cervical diskectomy and fusion, we then
      retrospectively reviewed standing preoperative lateral plain radiographs of the
      cervical spine, in addition to supine lateral cervical spine radiographs taken at
      the time of surgery, to assess: (1) the position of the AM relative to the
      corresponding cervical spinal level, and (2) whether or not the position of the
      AM relative to the subaxial cervical levels is different on preoperative standing
      films and intraoperative supine films. In these same 26 patients, we also
      measured the vertical distance between the AM and the location of each subaxial
      intervertebral disc space. These measurements were repeated for the hyoid bone as
      a control for each patient. RESULTS: The interobserver accuracy was 100% between
      observers for identifying the AM, hyoid bone, thyroid cartilage, and cricothyroid
      membrane, and 93% for carotid tubercle. The frequency with which anterior neck
      landmarks were palpable by the surgeon and assisting senior residents was as
      follows: AM (100%), hyoid bone (83%), thyroid cartilage and cricothyroid membrane
      (93%), and carotid tubercle (Surgeon: 63%, Resident: 57%, P = 0.79). There was
      100% correlation between the position of the mandibular angle in the preoperative
      standing lateral radiograph and the intraoperative supine lateral radiograph,
      compared with 65% with the hyoid bone. The distances between the AM or hyoid to
      each disc space did not vary significantly between preoperative and
      intraoperative radiographs (P > 0.05). CONCLUSION: The mandibular angle was shown
      to be the most consistently palpable landmark. Further, the distance from the
      mandible, measured on preoperative plain lateral cervical spine radiographs, is
      an accurate template to determine cervical spine levels during anterior cervical
      spine surgery.

PMID- 19404177
TI  - Cervical motion assessment using virtual reality.
AB  - STUDY DESIGN: Repeated measures of cervical motion in asymptomatic subjects.
      OBJECTIVES: To introduce a virtual reality (VR)-based assessment of cervical
      range of motion (ROM); to establish inter and intratester reliability of the VR
      based assessment in comparison with conventional assessment in asymptomatic
      individuals; and to evaluate the effect of a single VR session on cervical ROM.
      SUMMARY OF BACKGROUND DATA: Cervical ROM and clinical issues related to neck pain
      is frequently studied. A wide variety of methods is available for evaluation of
      cervical motion. To date, most methods rely on voluntary responses to an
      assessor's instructions. However, in day-to-day life, head movement is generally
      an involuntary response to multiple stimuli. Therefore, there is a need for a
      more functional assessment method, using sensory stimuli to elicit spontaneous
      neck motion. VR attributes may provide a methodology for achieving this goal.
      METHODS: A novel method was developed for cervical motion assessment utilizing an
      electromagnetic tracking system and a VR game scenario displayed via a head
      mounted device. Thirty asymptomatic participants were assessed by both
      conventional and VR-based methods. Inter and intratester repeatability analyses
      were performed. The effect of a single VR session on ROM was evaluated. RESULTS:
      Both assessments showed non-biased results between tests and between testers (P >
      0.1). Full-cycle repeatability coefficients ranged between 15.0 degrees and 29.2
      degrees with smaller values for rotation and for the VR assessment. A single VR
      session significantly increased ROM, with largest effect found in the rotation
      direction. CONCLUSION: Inter and intratester reliability was supported for both
      the VR-based and the conventional methods. Results suggest better repeatability
      for the VR method, with rotation being more precise than flexion/extension. A
      single VR session was found to be effective in increasing cervical motion,
      possibly due to its motivating effect.

PMID- 19404178
TI  - Outcome of conservative surgery for giant cell tumor of the sacrum.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: To estimate the clinical outcome
      of conservative surgery (intralesional curettage or partial excision) aided by
      effective intraoperative hemorrhage control in patients with giant cell tumors of
      the sacrum. SUMMARY OF BACKGROUND DATA: Giant cell tumors of the sacrum present a
      challenging therapeutic problem. Wide resection is associated with higher
      morbidity and spinal instability. Whether conservative surgery aided by effective
      intraoperative hemorrhage control can achieve low recurrence rates remains
      uncertain. METHODS: The clinical records of 24 patients with an average age of 35
      years who had undergone conservative surgery for sacral giant cell tumor between
      1996 and 2005 were evaluated retrospectively. The disease onset, tumor size,
      operation records, complications, follow-up status, and functional outcome were
      analyzed. RESULTS: The mean duration of follow-up was 58 months (median, 50
      months; range: 25-132 months). All the patients had a conservative procedure
      aided by intraoperative occlusion of the abdominal aorta. The mean estimated
      blood loss was 3217 mL. The mean length of the operation was 190 minutes. Seven
      (29.2%) patients developed recurrences. The mean time from the index surgical
      procedure to the first recurrence was 13 months (range: 8-31 months). The 5-year
      local recurrence-free survival rate was 69.6%. Seventeen (70.8%) patients
      retained normal urinary function and 16 (66.7%) patients preserved normal bowel
      function. No patients had urinary or bowel dysfunction when both S3 nerves were
      preserved. Ten (41.7%) patients had complications perioperatively or during the
      follow-up. Seven (29.2%) patients had wound complications. CONCLUSION:
      Considering the acceptable local recurrence rate, conservative surgery aided by
      effective control of intraoperative hemorrhage should be considered as an
      alternative procedure for patients with giant cell tumors of the sacrum. The
      advantages include lower morbidity, reduced neurologic deficits, speed and ease
      of the surgical procedure, reduced blood loss, preservation of spinal and pelvic
      continuity, and a low recurrence rate.

PMID- 19404179
TI  - Correction hinge in the compromised cord for severe and rigid angular kyphosis
      with neurologic deficits.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To report the use of a reliable and
      safe technique for the surgical management of severe and rigid angular kyphotic
      deformities with neurologic deficits. SUMMARY OF BACKGROUND DATA: Severe and
      rigid angular kyphotic deformity can result in difficult to treat neurologic
      deficits. Previously described techniques are an ordeal for both the patient and
      the surgeon and run the risk of damaging the compromised spinal cord because of
      stretch, compression, deformation, and direct intraoperative cord manipulation
      during the procedure. METHODS: Seventeen consecutive patients with neurologic
      deficits due to severe and rigid angular kyphotic deformity were treated with
      circumferential neurologic decompression and correction by one-shot in situ
      cantilever bending at the apex of the deformity with a fixed hinge in the
      compromised spinal cord. The procedure involved minimal manipulation, stretching,
      compression, and deformation of the vulnerable cord. Minimum follow-up after
      surgery was 2 years (range: 2.5-6.4 years). Mean Cobb angle of kyphotic deformity
      was 105.3 degrees (range: 85 degrees -121 degrees ). All patients exhibited
      neurologic deficits. There were 6, 7, and 4 patients classified as Frankel B, C,
      and D, respectively. Etiologic diagnoses were congenital kyphosis in 6 and
      postinfectious kyphosis in 11 patients. RESULTS: Mean operation time was 194
      minutes and average blood loss was 1621 mL. All patients showed neurologic
      improvement. Two of the Frankel B patients improved to Frankel E and 2 each to
      Frankel D and C. Two of the Frankel C patients improved to Frankel D, whereas 5
      improved to Frankel E. All Frankel D patients improved to Frankel E. Kyphotic
      deformity correction was 30% in the sagittal plane. Complications were minor.
      CONCLUSION: Circumferential neurologic decompression and one-shot cantilever
      bending correction with a fixed hinge in the compromised cord is a safe and
      effective alternative for surgical treatment of severe and rigid angular kyphotic
      deformities with neurologic deficits.

PMID- 19404180
TI  - Sagittal spinal posture after Pilates-based exercise in healthy older adults.
AB  - STUDY DESIGN: Longitudinal, repeated-measures study. OBJECTIVE: The aim of this
      study was to determine changes in sagittal spinal posture in older adults during
      standing and sitting after a Pilates-based exercise program. SUMMARY OF
      BACKGROUND DATA: Pilates exercise is purported to improve posture, however, few
      peer-reviewed articles are available to provide scientific support. Most previous
      studies were conducted in young dancers, and the effect of Pilates exercise on
      spinal posture in older adults remained unclear. METHODS: Thirty-four healthy
      older adults aged over 60 years volunteered for this study. A two-dimensional
      PEAK Motus motion analysis system was used to measure sagittal spinal angles.
      Participants were tested on 2 occasions before the exercise program to establish
      a baseline measure, and undertook a supervised Pilates-based exercise program
      twice weekly for 10 weeks. Participants were tested on another 2 occasions,
      immediately after the exercise program, and after a short-term follow-up.
      RESULTS: Baseline measures in both standing and sitting postures remained
      unchanged except for the lumbar spine angle in sitting. Immediately after the
      Pilates-based exercise program, older adults stood with slightly decreased
      thoracic flexion and sat with slightly increased lumbar extension. No significant
      differences were found during the follow-up period. CONCLUSION: The individually
      designed Pilates-based exercise program was feasible for healthy older adults,
      and the high attendance rate supports the suitability of the exercise program
      over a long period. Considering the variability of the baseline measure, small
      improvement was only observed in the thoracic kyphosis during standing. The long
      term effect of Pilates exercise requires further investigation.

PMID- 19404181
TI  - Polish adaptation of scoliosis research society-22 questionnaire.
AB  - STUDY DESIGN: Polish adaptation of the original version of Scoliosis Research
      Society (SRS) instrument. OBJECTIVE: The transcultural adaptation of SRS-22 and
      evaluation of its internal consistency. SUMMARY OF BACKGROUND DATA: High
      psychometric value of the SRS-22 Questionnaire has made it an effective
      evaluation instrument in clinically assessing the functional status of patients
      with adolescent idiopathic scoliosis. METHODS: First, 2 translators translated
      the original version into Polish. Afterwards, the translators identified
      differences between the translations and produced a consensus version. In the
      third stage, 2 native English speakers produced back translations. Finally, a
      team of 2 orthopedic surgeons, translators, a statistician and a psychologist
      reviewed all the translations to produce a prefinal version. The questionnaire
      was administered to 60 girls at the age of 16.6, SD 2.0 with adolescent
      idiopathic scoliosis treated with the Cotrel-Dubousset method in Pediatric
      Orthopaedics and Traumatology Clinic in Poznan. RESULTS: The internal consistency
      in the Polish version equaled 0.89 for the overall result and 0.81 for function,
      0.81 for pain, 0.80 for mental health, 0.77 for self-image, and 0.69 for
      treatment satisfaction domains, respectively. CONCLUSION: The Polish version of
      SRS-22 is characterized by high internal consistency for all domains and for the
      overall score, which makes it an evaluation tool after surgical treatment
      compatible with the original SRS-22.

PMID- 19404184
TI  - Re: Manchikanti L, Singh V, Falco FJ, et al. Cervical medial branch blocks for
      chronic cervical facet joint pain: a randomized, double-blind, controlled trial
      with one-year follow-up. Spine 2008;33:1813-20.

PMID- 19404182
TI  - Insertion of the artificial disc replacement: a cadaver study comparing the
      conventional surgical technique and the use of a navigation system.
AB  - STUDY DESIGN: Comparison of total disc replacement (TDR) with and without
      computer-assisted surgical navigation. OBJECTIVE: To test and evaluate the
      accuracy of computer-assisted navigation for the lumbar spine by comparing the
      traditional C-arm-aided insertion of an arthroplasty device to the navigation
      aided insertion of the implant. SUMMARY OF BACKGROUND DATA: Previous studies have
      shown that poor placement of the CHARITE disc can be correlated to worse clinical
      results. Because of parallax effect, exclusive use of fluoroscopy could make
      placement of the artificial disc less accurate. False positioning may also lead
      to spondylolisthesis, disc degeneration of the adjacent segment, subsidence of
      the disc, and failure of the implant. METHODS: Ten human cadaver spine specimens
      were used at 3 lumbar segments (L3-L4, L4-L5, and L5-S1). Before implantation,
      all artificial discs were planned for "ideal" placement on a digital computed
      tomography image. Fifteen lumbar intervertebral disc prostheses (Depuy, Raynham,
      MA) were placed using Vector Vision image guidance (BrainLAB AG, Munich,
      Germany), by an inexperienced TDR-surgeon. Fifteen lumbar intervertebral disc
      prostheses were placed with exclusive use of fluoroscopy by an experienced TDR
      surgeon. After insertion, DICOM computed tomography scans were analyzed using
      computer software to assess placement accuracy of each disc prosthesis. RESULTS:
      The navigated placement of the disc was significantly more accurate. Only 3
      navigated disc prostheses were suboptimal and none was poorly placed. CONCLUSION:
      Surgical computer-assisted navigation may be a useful tool in the hands of a
      spine surgeon to achieve more accurate placement of the disc prosthesis. Because
      of the parallax effect, computer-assisted navigation offers more placement
      accuracy than stan- dard fluoroscopy. Because the accurate placement of total
      disc prosthesis has been correlated with better clinical outcome, further study
      regarding the navigation of the TDR is essential.

PMID- 19404185
TI  - Re: Manchikanti L, Singh V, Falco FJE, et al. Cervical medial branch blocks for
      chronic cervical facet joint pain. A randomized, double-blind, controlled trial
      with one-year follow-up. Spine 2008;33:1813-20.

PMID- 19404187
TI  - Noninvasive evaluation of lower urinary tract function in children with cerebral
      palsy.
AB  - OBJECTIVE: The aim of this study was noninvasive evaluation of voiding function
      in children with cerebral palsy. DESIGN: Sixty children with cerebral palsy were
      enrolled in the study. Urinary system symptoms were recorded. Uroflowmetric tests
      were carried out, and postvoid residual volume was measured immediately after
      voiding by using a portable ultrasonic device developed for children. The
      expected age-related bladder capacity was calculated and compared with the
      observed bladder capacity. Uroflowmetric curves were evaluated and classified as
      normal (bell-shaped) and abnormal. RESULTS: Thirty-three of the children (55%)
      were symptomatic. In 17 (28.3%) of the children, postvoid residual urine was
      observed. There was a statistically significant difference between the expected
      bladder capacity (271.6 +/- 38.3 ml) and the observed bladder capacity (154.5 +/-
      111.8 ml) (P < 0.001). Observed bladder capacity was lower than the expected
      bladder capacity in 56 (93.3%) of the children. In the evaluation of the
      uroflowmetric charts, 22 (36.7%) children had abnormal curves. CONCLUSIONS:
      Bladder capacity is decreased in most children with cerebral palsy, and postvoid
      residue is present in an important proportion. Uroflowmetry and portable
      ultrasonic device combination is a noninvasive, well-tolerated, and efficient
      method in the first line evaluation of lower urinary tract function in children
      with cerebral palsy.

PMID- 19404188
TI  - Sensory nerve conduction studies in neuralgic amyotrophy.
AB  - Neuralgic amyotrophy is a painful, episodic peripheral nerve disorder localized
      to the brachial plexus. Sensory symptoms occur in 80% of the patients. We
      assessed the frequency of abnormalities in sensory nerve conduction studies of
      the lateral and medial antebrachial cutaneous, radial sensory, median sensory,
      and ulnar sensory nerves in 112 patients. Sensory nerve conduction studies showed
      abnormalities in <20% of nerves, even when the nerve was clinically affected. The
      lateral and medial antebrachial cutaneous nerves were most often abnormal, in 15%
      and 17% of nerves. No correlation with the presence or localization of clinical
      deficits was found. Brachial plexus sensory nerve conduction studies seem to be
      of little diagnostic value in neuralgic amyotrophy. Our findings also indicate
      that some sensory lesions may be in the nerve roots instead of the plexus. An
      examination of normal sensory nerve conduction studies does not preclude
      neuralgic amyotrophy as a diagnosis.

PMID- 19404189
TI  - Remote effects of dry needling on the irritability of the myofascial trigger
      point in the upper trapezius muscle.
AB  - OBJECTIVE: To investigate the remote effect of dry needling on the irritability
      of a myofascial trigger point in the upper trapezius muscle. DESIGN: Thirty-five
      patients with active myofascial trigger points in upper trapezius muscles were
      randomly divided into two groups: 18 patients in the control group received sham
      needling, and 17 patients in the dry-needling group received dry needling into
      the myofascial trigger point in the extensor carpi radialis longus muscle. The
      subjective pain intensity, pressure pain threshold, and range of motion of the
      neck were assessed before and immediately after the treatment. RESULTS:
      Immediately after dry needling in the experimental group, the mean pain intensity
      was significantly reduced, but the mean pressure threshold and the mean range of
      motion of cervical spine were significantly increased. There were significantly
      larger changes in all three parameters of measurement in the dry-needling group
      than that in the control group. CONCLUSIONS: This study demonstrated the remote
      effectiveness of dry needling. Dry needling of a distal myofascial trigger point
      can provide a remote effect to reduce the irritability of a proximal myofascial
      trigger point.

PMID- 19404190
TI  - Effects of amantadine in children with impaired consciousness caused by acquired
      brain injury: a pilot study.
AB  - OBJECTIVE: To conduct a pilot study of amantadine in children with impaired
      consciousness caused by acquired brain injury, to establish design feasibility,
      and to assess the effect on level of arousal and consciousness. DESIGN:
      Randomized, double-blind, placebo-controlled crossover trial. Seven subjects
      (mean age, 12.7 yrs) with an acquired brain injury (mean duration, 6 wks) were
      randomized to receive either 3 wks of placebo or amantadine, followed by a 1-wk
      washout period and then 3 wks of the other agent. Main outcome measures were the
      Coma/Near-Coma Scale and Coma Recovery Scale-Revised, each done three times per
      week. Subjective evaluations of change in arousal and consciousness by the parent
      and physician were done weekly. RESULTS: Five subjects completed the study. There
      was no significant difference in the slopes of recovery during either arm for the
      Coma/Near-Coma Scale (P = 0.24) or the Coma Recovery Scale-Revised (P = 0.28),
      although improvements in consciousness were noted by the physician during weeks
      when amantadine was given (P = 0.02). CONCLUSIONS: This study suggests that
      amantadine facilitates recovery of consciousness in pediatric acquired brain
      injury and provides important information necessary to design future more
      definitive studies.

PMID- 19404191
TI  - Hip pain, instability caused by labral tears, and an acetabular giant cell tumor.

PMID- 19404192
TI  - Rectus muscle strain akin to a mass lesion of the thigh: sonography distinguishes
      the nuance.

PMID- 19404193
TI  - Antidepressant-like effects of nicotine and mecamylamine in the mouse forced swim
      and tail suspension tests: role of strain, test and sex.
AB  - Clinical and preclinical evidence suggest a role of nicotinic acetylcholine
      receptors in major depression. In humans, both nicotine and the nonselective
      nicotinic acetylcholine receptor antagonist mecamylamine ameliorate depressive
      symptoms. Similarly, both drugs produce antidepressant-like effects in rodents.
      In rats, the most consistent finding is antidepressant-like effects of nicotine,
      but not mecamylamine. Conversely, in mice, several studies show antidepressant
      like effects of mecamylamine, whereas nicotine has shown modest or no effects.
      These contradictory results might be because of genetic differences. Here, we
      compared the effects of nicotine and mecamylamine in females and males of NMRI,
      C57BL/6J and BALB/c mice using the mouse forced swim (mFST) and tail suspension
      tests (mTST). In the mFST, mecamylamine, but not nicotine, increased swim
      distance in NMRI mice. In contrast, nicotine, but not mecamylamine, increased
      swim distance in C57BL/6J mice. Both drugs increased swim distance in BALB/c
      mice. Effects in the mFST were independent of sex. In the mTST, mecamylamine
      decreased immobility in NMRI mice only, independent of sex. Nicotine was devoid
      of effects in the mTST, except in female C57BL/6J mice, where it increased
      immobility. We hypothesize that nicotine and mecamylamine produce antidepressant
      like effects through partially different mechanisms.

PMID- 19404194
TI  - L-DOPA attenuates hyperactivity of Roborovskii hamsters.
AB  - The Roborovskii hamster (Phodopus roborovskii) has been shown to have high
      locomotor activity (hyperactivity) and low dopamine concentrations in the brain.
      We hypothesized that low brain dopamine concentrations play a role in the
      pathogenesis of hyperactivity. In this study, therefore, we investigated the
      effects of L-DOPA (L-3,4-dihydroxyphenylalanine), the precursor of dopamine, on
      the locomotor activity of Roborovskii hamster to verify the above hypothesis. An
      open field test was employed to measure the locomotor activity. Administration of
      L-DOPA dose-dependently decreased locomotor activity including distance of path
      and time spent moving. L-DOPA increased the brain concentration of dopamine and
      its metabolite 3,4-dihydroxyphenylacetic acid. Concurrently, L-DOPA caused
      increase of norepinephrine, decrease of serotonin, and atypical alteration of
      their metabolite concentrations. These findings mainly suggest that in
      Roborovskii hamsters, a low level of brain dopamine neurotransmission is one of
      the reasons for hyperactivity, and hyperactivity can be attenuated by L-DOPA.

PMID- 19404195
TI  - Helicobacter pylori infection and chronic atrophic gastritis: associations
      according to severity of disease.
AB  - BACKGROUND: Helicobacter pylori infection is an established risk factor for
      chronic atrophic gastritis. However, estimates of the strength of this
      association have varied widely, possibly due to clearance of the infection in
      severe stages of chronic atrophic gastritis, which may lead to underestimation of
      the association. We assessed the association of H. pylori infection with chronic
      atrophic gastritis according to severity of disease. METHODS: We measured serum
      pepsinogen I and II (as surrogates for chronic atrophic gastritis) and antibodies
      against H. pylori by ELISA in 9444 men and women aged 50-74 years in a population
      based study in Saarland, a state of Germany. The association between H. pylori
      and chronic atrophic gastritis (defined as pepsinogen I <70 ng/mL and pepsinogen
      I/II-ratio <3) was analyzed after stratification of chronic atrophic gastritis
      cases by quintiles of pepsinogen I as proxy marker for severity of chronic
      atrophic gastritis. RESULTS: When all cases were included, the odds ratio for the
      association with Chronic atrophic gastritis for H. pylori infection alone was 2.9
      (95% confidence interval 2.3-3.6); it was 4.1 (3.2-5.2), for H. pylori infection
      that was positive for the presence of Ig G antibodies specific to the cytotoxin
      associated gene A (CagA) protein-a well-established virulence factor of H.
      pylori. These ORs ranged from 11 (5.2-22) and 16 (7.7-34) for the quintile of
      cases with highest pepsinogen I (least severe cases) to 1.0 (0.7-1.6) and 0.9
      (0.5-1.5) for the quintile of cases with lowest pepsinogen I (most severe cases).
      Five of 7 cases with CagA-seropositivity but negative H. pylori serostatus (a
      pattern indicative of past infection) were in the group of most severe cases.
      CONCLUSIONS: Our results support the hypothesis of major underestimation of the
      association of H. pylori and chronic atrophic gastritis, due to clearance of the
      infection in advanced stages of the disease. These results suggest that the
      association is much stronger than estimated by most epidemiologic studies to
      date.

PMID- 19404196
TI  - Influence of angiotensinogen and angiotensin-converting enzyme polymorphisms on
      cardiac hypertrophy and improvement on maximal aerobic capacity caused by
      exercise training.
AB  - BACKGROUND: The allele threonine (T) of the angiotensinogen has been associated
      with ventricular hypertrophy in hypertensive patients and soccer players.
      However, the long-term effect of physical exercise in healthy athletes carrying
      the T allele remains unknown. We investigated the influence of methionine (M) or
      T allele of the angiotensinogen and D or I allele of the angiotensin-converting
      enzyme on left-ventricular mass index (LVMI) and maximal aerobic capacity in
      young healthy individuals after long-term physical exercise training. DESIGN:
      Prospective clinical trial. METHODS: Eighty-three policemen aged between 20 and
      35 years (mean+/-SD 26+/-4.5 years) were genotyped for the M235T gene
      angiotensinogen polymorphism (TT, n = 25; MM/MT, n = 58) and angiotensin
      converting enzyme gene insertion/deletion (I/D) polymorphism (II, n = 18; DD/DI,
      n = 65). Left-ventricular morphology was evaluated by echocardiography and
      maximal aerobic capacity (VO2peak) by cardiopulmonary exercise test before and
      after 17 weeks of exercise training (50-80% VO2peak). RESULTS: Baseline VO2peak
      and LVMI were similar between TT and MM/MT groups, and II and DD/DI groups.
      Exercise training increased significantly and similarly VO2peak in homozygous TT
      and MM/MT individuals, and homozygous II and DD/DI individuals. In addition,
      exercise training increased significantly LVMI in TT and MM/MT individuals
      (76.5+/-3 vs. 86.7+/-4, P = 0.00001 and 76.2+/-2 vs. 81.4+/-2, P = 0.00001,
      respectively), and II and DD/DI individuals (77.7+/-4 vs. 81.5+/-4, P = 0.0001
      and 76+/-2 vs. 83.5+/-2, P = 0.0001, respectively). However, LVMI in TT
      individuals was significantly greater than in MM/MT individuals (P = 0.04). LVMI
      was not different between II and DD/DI individuals. CONCLUSION: Left-ventricular
      hypertrophy caused by exercise training is exacerbated in homozygous TT
      individuals with angiotensinogen polymorphism.

PMID- 19404197
TI  - Association of serum adiponectin levels and coronary flow reserve in women with
      normal coronary angiography.
AB  - BACKGROUND: Women may have atypical clinical presentations and atypical risk
      factors of coronary artery disease. Adiponectin has anti-insulin-resistant
      properties and antiatherogenic effects. We investigated the association between
      serum adiponectin levels and coronary flow reserve (CFR) in women with normal
      coronary arteries. METHODS: CFR was assessed in 45 consecutive women (mean age
      54.2+/-9.2 years) with normal epicardial coronary arteries by coronary
      angiography. Serum adiponectin, C-reactive protein, insulin, and glucose levels
      were examined and Homeostasis Model Assessment for Insulin Resistance index was
      calculated. Peak diastolic coronary flow velocities were measured in distal left
      anterior descending artery at baseline and after dipyridamole infusion by
      transthoracic pulsed wave Doppler echocardiography. CFR was calculated as the
      ratio of hyperemic to baseline peak diastolic velocities. A CFR value > or =2 was
      accepted as normal. RESULTS: Adiponectin levels were lower in patients with
      impaired CFR than those with normal CFR (7.1+/-2.3 vs. 13.8+/-6.7 microg/ml
      P<0.001). Adiponectin levels were correlated with CFR (r=0.531, P<0.001) and
      inversely correlated with C-reactive protein (r=-0.308, P=0.047), insulin (r=
      0.426, P=0.008), and Homeostasis Model Assessment for Insulin Resistance index
      (r=-0.442, P=0.004). Adiponectin levels of < or =8.5 muU/ml had 83% sensitivity
      and 93% specificity [receiver operating characteristic area 0.084, P<0.001, 95%
      confidence interval (0.56-1.08)] for predicting impaired CFR. CONCLUSION:
      Decreased adiponectin levels are associated with impaired CFR in women with
      normal epicardial coronary arteries and hypoadiponectinemia may be a risk factor
      for impaired CFR in women.

PMID- 19404198
TI  - Cancer incidence pattern in Cordoba, Argentina.
AB  - Cancer is the second cause of death in Argentina; nevertheless the distribution
      of the cancer incidence rates throughout the country is unknown. This study was
      conducted to describe cancer incidence patterns in Cordoba Province. Incidence
      data were supplied by the Government Cordoba Cancer Registry. Demographic
      information (age, sex, and place of residence) and diagnosis, certified by a
      pathologist, about all incident cases from June 2003 to May 2005 by type and 5
      year age groups were obtained. Comparison of the incidence rate of cancer in
      various counties was performed by using standardized incidence rates (SIR) per
      100,000 inhabitants using the world standard population. Estimated SIRs were used
      to build up incidence maps. Two indicators were created: sex ratio and site
      specific ratio. Mixed Poisson models were fitted. Taken as a whole for all
      counties, SIR was 121.42 and 141.57 for men and women, respectively. The most
      common sites in men were prostate (13.62), lung (10.12), colon (7.53), and
      bladder (7.03); in women were breast (22.51) and colon (3.31). The highest and
      lowest rates were in urban and rural areas, respectively. Cancer registry has a
      pivotal role in cancer control. Such information is the primary resource of
      information not only for epidemiological research on cancer determinants but also
      for planning and evaluating health services for the policies of prevention,
      diagnosis and treatment of the disease.

PMID- 19404199
TI  - Optimal management of sternoclavicular septic arthritis.
AB  - Sternoclavicular septic arthritis is uncommon. We present a case occurring after
      closed upper limb trauma and highlight the importance of clinical recognition and
      prompt computed tomography imaging. Appropriate, timely, antibiotic and surgical
      therapy is required to limit bony destruction and potential complications.

PMID- 19404200
TI  - Tropical calcific pancreatitis and its association with CTRC and SPINK1 (p.N34S)
      variants.
AB  - BACKGROUND: Tropical calcific pancreatitis (TCP) is a relatively common form of
      chronic pancreatitis in parts of Asia and Africa. The SPINK1 variant p.N34S is
      strongly associated with TCP, but other genetic factors remain to be defined.
      Chymotrypsinogen C (CTRC) degrades trypsinogen and loss-of-function variants have
      been found in European patients with chronic pancreatitis. Preliminary data
      indicate that CTRC might increase the risk for TCP. MATERIALS AND METHODS: We
      selected 150 Indian TCP patients and 150 Indian controls to perform mutational
      screening of the complete coding region of CTRC and exon 3 of SPINK1. We
      performed in-silico analysis and functional studies of novel CTRC variants.
      RESULTS: We identified eight variants among this sample. Three were synonymous
      and c.180 C>T was significantly enriched in patients (odds ratio=2.09; 95%
      confidence interval=1.19-3.67; P=0.03). We identified a novel nonsynonymous CTRC
      (p.G61R) variant in one of 146 patients (0.7%), but absent from controls. In
      silico analysis showed that this variant affected a conserved residue, and
      functional analysis showed that p.G61R results in a complete loss of CTRC
      secretion from transiently transfected human embryonic kidney 293T cells. SPINK1
      p.N34S was present in 31.8% of patients compared with 4.7% in controls, there was
      no significant cosegregation with CTRC variants. CONCLUSION: The contribution of
      CTRC variants to TCP is relatively small, but the identification of novel loss-of
      function variants (p.G61R) underscores the importance of the trypsinogen pathway
      in causing TCP.

PMID- 19404201
TI  - Complicated wireless capsule enteroscopy in a patient with Crohn's disease.
AB  - An 18-year-old male experienced a first episode of Crohn's disease with
      inflammation of the colon, stenosis of small intestine and a fistula of the anal
      sphincter. After resection of the fistula and 30 cm of proximal ileum the patient
      remained free of symptoms under medication with azathioprine and mesalazine for 6
      years. Then, blood in the stool occurred. Diagnostic work-up - gastroscopy and
      colonoscopy 2004 and 2006, magnetic resonance enteroclysis 2004 and 2006 and
      wireless capsule enteroscopy 2006 - revealed slight inflammation in the ileum but
      no bleeding source. The bleeding ceased, but after 2 uneventful years abdominal
      cramps appeared and diagnostic work-up (magnetic resonance enteroclysis,
      radiograph) located the capsule still in the terminal ileum proximal to an
      inflamed stenosis. Corticosteroids were subscribed for 4 weeks, but the capsule
      stayed in place. Surgery was discussed, but denied by the patient. Finally, the
      capsule could be taken out by double balloon enteroscopy.

PMID- 19404202
TI  - Severe hepatitis associated with the use of black cohosh: a report of two cases
      and an advice for caution.
AB  - In spite of the fact that severe side effects have been reported, black cohosh
      [Actaea racemosa (syn. Cimifuga racemosa)] is likely to be one of the most
      popular herbs used in the treatment of postmenopausal symptoms and menstrual
      dysfunction. We report the cases of two patients, one with submassive liver
      necrosis and the other with chronic hepatitis most likely related to the use of
      two different preparations containing black cohosh. This represents another
      advice for caution concerning this popular preparation of inconsistent
      therapeutic value.

PMID- 19404203
TI  - Hepatocellular adenoma in advanced-stage fatty liver disease.
AB  - Hepatocellular adenomas are defined as benign hepatocellular neoplasms occurring
      in otherwise near normal liver and adenomatosis as 10 or more such lesions. We
      present a case of a 45-year-old man with radiological adenomatosis,
      histologically confirmed with resection of one lesion, arising within advanced
      stage nonalcoholic fatty liver disease (nearly cirrhotic). Hepatocellular
      adenomas have recently been divided into four categories and the lesion in the
      present case had morphologic and immunohistochemical features of an inflammatory
      hepatocellular adenoma. These findings demonstrate that, in contrast to the
      current dogma, nodules within advanced-stage liver disease may rarely be best
      classified as adenomas. This should be considered in the radiological
      differential diagnosis when assessing a patient's suitability for
      transplantation.

PMID- 19404204
TI  - Validation of the Spanish Work Productivity and Activity impairment
      questionnaire: Crohn's disease version.
AB  - BACKGROUND: The Work Productivity and Activity Impairment questionnaire has only
      been partially validated in Crohn's disease. OBJECTIVE: To test the Work
      Productivity and Activity Impairment questionnaire for use in Crohn's disease
      patients. METHODS: A validated Spanish translation of the test was assessed.
      'Discriminant validity' was evaluated by comparing Work Productivity and Activity
      Impairment scores in Crohn's disease patients with active versus inactive
      disease, and in patients versus healthy controls. 'Convergent validity' was
      tested comparing Work Productivity and Activity Impairment questionnaire with
      quality of life, Crohn's disease activity index and a debriefing questionnaire.
      'Reproducibility' of repeated tests was evaluated by comparing two Work
      Productivity and Activity Impairment measures obtained 2 weeks apart in stable
      patients. 'Responsiveness' was determined by comparing Work Productivity and
      Activity Impairment values in the same patients during a flare-up of Crohn's
      disease and during remission. The Wilcoxon test for paired data and the Mann
      Whitney U test for unpaired data were used for comparisons. RESULTS: One hundred
      and six patients were included in the various steps of the analysis. All Work
      Productivity and Activity Impairment parameters showed adequate discriminant and
      convergent validity and responsiveness. The test's reproducibility was also
      adequate, except for the evaluation of presenteeism (the impairment of
      productivity while working). CONCLUSION: The Spanish Work Productivity and
      Activity Impairment questionnaire is a valid and reliable measurement of work
      impairment in Crohn's disease. Unexpectedly, the test did not present
      satisfactory reproducibility for the evaluation of presenteeism. The reliability
      of this last finding should be evaluated in further studies.

PMID- 19404206
TI  - Treatment of chronic hepatitis C in sickle cell disease and thalassaemic patients
      with interferon and ribavirin.
AB  - BACKGROUND/AIM: Hepatic complications are a major cause of death in patients with
      congenital anaemia and chronic hepatitis C. Ribavirin is usually contraindicated
      in patients with haemolytic anaemia. This pilot study evaluated the efficacy and
      safety of antiviral treatment in patients with sickle cell disease (SCD) or beta
      thalassaemia major (TM). METHODS: Eleven consecutive SCD and TM patients were
      included. Interferon monotherapy was administrated in the two first thalassaemic
      patients. Other patients received combination therapy with full dose of pegylated
      interferon 2b and increasing doses of ribavirin, starting with a low dose of
      ribavirin (400 mg/day). RESULTS: Hepatitis C virus genotypes were 1 or 4 in nine
      cases. A sustained virological response achieved in five of 11 patients despite
      unfavourable factors to response (genotypes, nonresponders to an earlier
      treatment). Haemoglobin level at the end of treatment was higher than baseline
      levels in five of six SCD patients. No SCD patient needed a transfusion during
      and after treatment period, neither presented vasoocclusive crisis. The mean
      increase in transfusion requirements was 32.5% in the thalassaemic group.
      CONCLUSION: A sustained virological response can be obtained in SCD and TM
      patients. No earlier study of excellent haematological tolerance among SCD
      patients under ribavirin has been reported to date. The results of this study
      suggest that full dose ribavirin could be used from the start of treatment in SCD
      patients.

PMID- 19404207
TI  - Differential ferritin expression is associated with iron deficiency in coeliac
      disease.
AB  - BACKGROUND: Sixty percent of people with coeliac disease (CD) are iron deficient.
      Many, however, remain iron replete despite the disease. AIMS: (i) To characterize
      the changes in duodenal iron transport proteins in CD with and without iron
      deficiency. (ii) To examine if iron-activated gut lymphocytes can inhibit iron
      export in an enterocyte cell model. METHODS: Endoscopic duodenal biopsies were
      collected from patients with normal duodenum with and without iron deficiency
      anaemia and untreated CD sufferers with iron deficiency (n=10 each group). mRNA
      expression of iron transport proteins was determined by quantitative real time
      PCR. Protein localization and expression was determined from histology sections
      in patients with normal duodenum (n=20), and patients with untreated CD with and
      without iron deficiency (n=20). In addition, CaCo2 cells were cocultured with
      iron-activated lymphocytes 55Fe was used to determine the effect on CaCo2 cell
      iron transport. RESULTS: The expression of divalent metal transporter 1 and
      ferroportin was increased in CD with or without iron deficiency. Ferritin
      expression was increased in CD but only in those with associated iron deficiency.
      TNF-alpha produced by activated lymphocytes inhibited iron export from CaCo2
      cells. CONCLUSION: Increased enterocyte ferritin expression may promote iron
      deficiency in CD and this effect seems to be dependent upon TNF-alpha expression
      in gut lymphocytes.

PMID- 19404208
TI  - Jaundice revealing a k light chain myeloma because of liver light chain deposits.
AB  - We report the case of a 77-year-old man referred for jaundice and diagnosed with
      intrahepatic light chain deposit as primary manifestation of a kappa light chain
      multiple myeloma. Jaundice is a very rare way of presentation for myeloma. In our
      observation, diagnosis was made by liver biopsy, which found light chain deposits
      infiltrating perisinusoidal spaces. We discuss jaundice's possible mechanisms in
      myeloma.

PMID- 19404205
TI  - Changing prevalence of upper gastrointestinal disease in 28 893 Koreans from 1995
      to 2005.
AB  - OBJECTIVES: Changes in the pattern of gastrointestinal diseases in a population
      tend to be influenced by changes in diet and lifestyle. Shifts in
      gastrointestinal disease from 1995 to 2005 in Korea were evaluated,
      retrospectively. METHODS: Seventeen nationwide medical centers participated in
      this study. The cross-sectional review of endoscopic findings in 28 893 patients
      included 8441 patients from 1995, 10 350 patients from 2000, and 10 102 patients
      from 2005. RESULTS: The prevalence of reflux esophagitis increased from 1.8% in
      1995 to 5.9% in 2000 and 9.1% in 2005 (P<0.001, the P value was only for the
      comparison between 1995 and 2005, the followings were as same). The prevalence of
      peptic ulcer diseases was 18.0% in 1995, 19.1% in 2000, and 20.2% in 2005
      (P<0.001). Although no significant differences were noted in duodenal ulcers
      (8.4, 8.7, and 8.2%, P=0.449), gastric ulcers showed an increasing trend (9.6,
      10.5, and 12.0%, P<0.001). The prevalence of gastric cancer increased from 3.4%
      in 1995 to 4.5% in 2000 (P<0.001), but then decreased to 2.4% in 2005 (P<0.001).
      The incidence of advanced gastric cancer was 2.5, 3.2, and 1.3%, respectively
      (P<0.001), and that of early gastric cancer remained constant with rates of 0.8%,
      1.3, and 1.1%, respectively (P=0.056). CONCLUSION: The cross-sectional review of
      data collected in 1995, 2000, and 2005 showed an increase in reflux esophagitis
      and peptic ulcer diseases. Meanwhile, the prevalence of gastric cancer increased
      until 2000, but decreased in 2005.

PMID- 19404209
TI  - Gastrointestinal stromal tumor complicated by Streptococcus milleri bacteremia
      and liver abscess.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms
      of the gastrointestinal tract. Often discovered incidentally, GISTs can present
      with nonspecific abdominal symptoms or more overt symptoms of bleeding,
      obstruction, or perforation. Despite a myriad of clinical presentations,
      bacteremia associated with a GIST has not been described. In this report, we
      present an unusual clinical case that illustrates how GISTs can become infected,
      and demonstrate the importance of Streptococcus milleri bacteremia as an
      indicator of possible underlying gastrointestinal neoplasm.

PMID- 19404211
TI  - A phase I study of amrubicin and carboplatin for previously untreated patients
      with extensive-disease small cell lung cancer.
AB  - BACKGROUND: Amrubicin and cisplatin are active in the treatment of small cell
      lung cancer (SCLC), and carboplatin is an analogue of cisplatin with less
      nonhematological toxicity. The appropriate dose of amrubicin and carboplatin
      combination chemotherapy for previously untreated patients with extensive-disease
      (ED) SCLC has not been established. PURPOSE: To determine the maximum-tolerated
      dose and dose-limiting toxicity (DLT) of amrubicin and carboplatin in ED-SCLC.
      PATIENTS AND METHODS: Eligibility criteria were chemotherapy-naive ED-SCLC
      patients, performance status 0-1, age < or =75, and adequate hematological,
      hepatic, and renal function. Patients received escalating amrubicin doses under a
      fixed target area under the curve (AUC) 5 of carboplatin (Chatelut formula).
      Amrubicin and carboplatin were administered by intravenous (IV) infusion on days
      1, 2, and 3, and day 1, respectively. The initial dose of amrubicin was 30
      mg/m(2), and the dose was escalated to 35 and 40 mg/m(2). RESULTS: Sixteen
      patients were enrolled and 15 eligible patients were evaluated. One of six
      patients in level 1, one of six in level 2, and three of three in level 3
      experienced DLTs. The presentation of DLTs included neutropenia, leukopenia,
      thrombocytopenia, febrile neutropenia, and liver dysfunction. Evaluation of
      responses were two complete response, nine partial response, three stable
      disease, and one progressive disease (response rate 73%), and the median survival
      time was 13.6 months. The maximum-tolerated doses of amrubicin and carboplatin
      were determined as 40 mg/m(2) and AUC 5. A dose of 35 mg/m(2) amrubicin and
      carboplatin AUC 5 was recommended in this regimen. CONCLUSIONS: This regimen is
      associated with an acceptable tolerability profile, and warrants evaluation in
      the phase II setting.

PMID- 19404212
TI  - Patterns of local and nodal failure in malignant pleural mesothelioma after
      extrapleural pneumonectomy and photon-electron radiotherapy.
AB  - INTRODUCTION: Multimodality therapy including extrapleural pneumonectomy (EPP),
      chemotherapy, and radiotherapy (RT) is often recommended for fit patients with
      early stage malignant pleural mesothelioma. Planning RT after an EPP is difficult
      due to the large target area, the high doses required to prevent recurrence, and
      the proximity of critical structures. We studied patterns of local and nodal
      recurrence in patients treated at our institution with EPP and RT, and whether
      advanced treatment planning techniques, such as intensity modulated radiotherapy
      (IMRT), could have been of potential benefit. METHODS: From 1993 to 2008, 86
      patients with malignant pleural mesothelioma underwent EPP followed by
      hemithoracic RT (median dose: 54 Gy). The RT technique included a combination of
      photons and electrons to maximize dose to the target, whereas minimizing dose to
      normal tissues. After treatment, patients were followed with serial imaging and
      patterns of local and nodal failure were studied. RESULTS: Median follow-up time
      for 78 analyzed patients was 17 months. Eight percent were in stage I, 35% stage
      II, 55% stage III, and 2% stage IV. Ten percent of all patients developed late
      grade 3 pulmonary toxicity and no patient died of RT. Fifteen patients failed in
      local and/or nodal sites and did not have a distant component to their failure
      pattern. Of these 15 patients, 10 failed in regions of dose inhomogeneity and
      could have possibly benefited from IMRT. CONCLUSIONS: The photon-electron
      technique was tolerable, but IMRT may provide better target coverage in some
      patients. IMRT's advantages must be balanced against the increased risk of fatal
      pulmonary toxicity.

PMID- 19404210
TI  - XM02, the first biosimilar G-CSF, is safe and effective in reducing the duration
      of severe neutropenia and incidence of febrile neutropenia in patients with small
      cell or non-small cell lung cancer receiving platinum-based chemotherapy.
AB  - BACKGROUND: Recombinant granulocyte colony-stimulating factors such as Neupogen
      are used to treat chemotherapy-induced neutropenia. The aim of the study was to
      show that a new granulocyte colony-stimulating factor, XM02, is as safe and
      effective as Neupogen in the treatment of chemotherapy-induced neutropenia in
      patients with small cell or non-small cell lung cancer. PATIENTS AND METHODS: A
      total of 240 patients receiving platinum-based chemotherapy were randomized in
      cycle 1 to treatment with daily injections (subcutaneous 5 microg/kg/d) of XM02
      (n = 160) or Filgrastim Neupogen (n = 80) for at least 5 days and a maximum of 14
      days. In subsequent cycles, all patients received XM02. RESULTS: The mean
      duration of severe neutropenia was 0.5 and 0.3 days in cycle 1 for XM02 and
      Filgrastim, respectively. In the analysis of covariance for duration of severe
      neutropenia in cycle 1, the estimated treatment difference "XM02 minus
      Filgrastim" was 0.157 days, with 95% confidence level (-0.114 days, 0.428 days),
      which was included in the prespecified equivalence range (-1, 1). There was no
      statistically significant difference of the end point incidence of febrile
      neutropenia in cycle 1 between XM02 and Filgrastim (p = 0.2347). The adverse
      event profile was similar between XM02 and Filgrastim. CONCLUSION: XM02
      demonstrated similar efficacy and safety profile as the reference medication
      Filgrastim in cycle 1. In conclusion, treatment with XM02 is beneficial in
      ameliorating severe neutropenia and febrile neutropenia in lung cancer patients
      receiving myelosuppressive chemotherapy. XM02 is safe and well tolerated in the
      doses applied in this study.

PMID- 19404213
TI  - A phase II study of concurrent chemoradiation with weekly docetaxel, carboplatin,
      and radiation therapy followed by consolidation chemotherapy with docetaxel and
      carboplatin for locally advanced inoperable non-small cell lung cancer (NSCLC).
AB  - INTRODUCTION: The current standard of care for good performance status patients
      with locally advanced non-small cell lung carcinoma is concurrent chemoradiation,
      although a clearly superior regimen has not been identified. Docetaxel has been
      shown to possess good single-agent activity against non-small cell lung cancer
      (NSCLC) and radiosensitizing properties, both alone and synergistically with
      carboplatin. We undertook this phase II study to determine the safety and
      efficacy of weekly docetaxel-carboplatin and concurrent radiation therapy
      followed by docetaxel-carboplatin consolidation for the treatment of locally
      advanced NSCLC. METHODS: Sixty-seven patients having previously untreated stage
      IIIA or IIIB unresectable NSCLC were enrolled, with 61 patients evaluated for
      endpoints. Docetaxel 20 mg/m IV infusion over 30 minutes followed by carboplatin
      area under the curve = 2 over 30 minutes was administered weekly during
      concurrent thoracic radiotherapy. After 3 week rest, consolidation docetaxel 75
      mg/m(2) IV infusion over 60 minutes and carboplatin area under the curve = 6 over
      30 minutes was administered every 3 weeks for two cycles. Concurrent thoracic
      radiation consisted of 45 Gy (1.8 Gy fractions 5 d/wk for first 5 weeks) followed
      by 18 Gy boost (2.0 Gy fractions 5 d/wk for 2 weeks) for a total dose of 63 Gy.
      RESULTS: One and 2 years overall survival rates were 45 and 20%, respectively.
      Progression free survival at 1 year was 27%. Median survival time was 12 months.
      Median time to progression was 8 months. The primary hematologic toxicity was
      leukopenia. The primary nonhematologic toxicity was esophagitis. CONCLUSION: The
      administered regimen of weekly docetaxel-carboplatin and concurrent radiation
      therapy followed by docetaxel-carboplatin consolidation has acceptable toxicity
      profile. However, the overall survivals at 1 and 2 years are somewhat
      disappointing.

PMID- 19404214
TI  - Classification by mass spectrometry can accurately and reliably predict outcome
      in patients with non-small cell lung cancer treated with erlotinib-containing
      regimen.
AB  - PURPOSE: Although many lung cancers express the epidermal growth factor receptor
      and the vascular endothelial growth factor, only a small fraction of patients
      will respond to inhibitors of these pathways. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MS) has shown promise in
      biomarker discovery, potentially allowing the selection of patients who may
      benefit from such therapies. Here, we use a matrix-assisted laser
      desorption/ionization MS proteomic algorithm developed from a small dataset of
      erlotinib-bevacizumab treated patients to predict the clinical outcome of
      patients treated with erlotinib alone. METHODS: Pretreatment serum collected from
      patients in a phase I/II study of erlotinib in combination with bevacizumab for
      recurrent or refractory non-small cell lung cancer was used to develop a
      proteomic classifier. This classifier was validated using an independent
      treatment cohort and a control population. RESULT: A proteomic profile based on
      11 distinct m/z features was developed. This predictive algorithm was associated
      with outcome using the univariate Cox proportional hazard model in the training
      set (p = 0.0006 for overall survival; p = 0.0012 for progression-free survival).
      The signature also predicted overall survival and progression-free survival
      outcome when applied to a blinded test set of patients treated with erlotinib
      alone on Eastern Cooperative Oncology Group 3503 (n = 82, p < 0.0001 and p =
      0.0018, respectively) but not when applied to a cohort of patients treated with
      chemotherapy alone (n = 61, p = 0.128). CONCLUSION: The independently derived
      classifier supports the hypothesis that MS can reliably predict the outcome of
      patients treated with epidermal growth factor receptor kinase inhibitors.

PMID- 19404215
TI  - Analysis of the T descriptors and other prognosis factors in pathologic stage I
      non-small cell lung cancer in China.
AB  - BACKGROUND: The seventh edition of the tumor, node, metastasis Classification of
      Malignant Tumors is due to be published in 2009. The recommendations of
      International Association for the Study of Lung Cancer for changes to the T
      descriptors have been published. We combined this new parameter with other well
      established prognostic factors and performed multivariate survival analyses to
      validate its value in Chinese stage I non-small cell lung cancer (NSCLC).
      METHODS: We try to validate the new staging project in 325 patients who underwent
      complete surgical resection for stage I NSCLC in Single Institution of Shanghai
      Chest Hospital from 1998 to 2003. Variables in the analysis included age, gender,
      performance status, history of smoking, pathologic type, type of resection
      (pneumonectomy, lobectomy, and bilobectomy), tumor size (greatest dimension of
      tumor), T-status (T1 or T2), type of lymph node resection (systematic mediastinal
      lymphadenectomy or mediastinal lymph node sampling), lymphovascular vessel
      invasion, and adjuvant chemotherapy. RESULTS: The 5-year overall survival (OS) of
      patients whose tumor measured no larger than 2 cm in largest diameter or larger
      than 2 cm but no larger than 3 cm were 75.49 and 74.58%, respectively. For those
      with tumors measured larger than 3 cm but smaller than 5 cm or larger than 5 cm
      but smaller than 7 cm were 60.87 and 55.63%. The 5-year OS of patients whose
      tumor measured larger than 7 cm was 46.15% (p = 0.025). The 5-year disease-free
      survival rates of patients whose tumor measured no larger than 2 cm in largest
      diameter or larger than 2 cm but no larger than 3 cm were 67.65 and 66.67%,
      respectively. For those with tumors measured larger than 3 cm but smaller than 5
      cm or larger than 5 cm but smaller than 7 cm were 53.14 and 52.63%. The 5-year
      disease-free survival rate of patients whose tumor measured larger than 7 cm was
      30.77% (p = 0.009). Multivariate analyses revealed that age, gender, type of
      resection (pneumonectomy, lobectomy, and bilobectomy), tumor size (greatest
      dimension of tumor), type of lymph node resection (systematic mediastinal
      lymphadenectomy or mediastinal lymph node sampling), and lymphovascular vessel
      invasion were significant predictive factors for OS. CONCLUSIONS: The tumor size
      is a significant independent prognostic factors in stage I NSCLC.

PMID- 19404216
TI  - Epidermal growth factor receptor gene in primary tumor and metastatic sites from
      non-small cell lung cancer.
AB  - INTRODUCTION: The majority of patients with non-small cell lung cancer (NSCLC)
      develop distant metastases. Epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors are capable of reducing brain and adrenal metastases. However,
      the EGFR status may be discordant between primary NSCLC and the corresponding
      metastases. METHODS: Using fluorescence in situ hybridization (FISH) analysis,
      the EGFR gene status was evaluated in a series of 38 cerebral or adrenal
      metastases collected from two institutions and in the corresponding primary
      tumors. Also, EGFR mutational analysis was performed using direct sequencing on
      the cerebral metastases. RESULTS: EGFR FISH was positive in 28% of the primary
      tumors and in 45% of the metastases (p < 0.05). Among the seven cases FISH
      positive at the metastatic site but negative in the primary tumor, six were brain
      metastases, and one was an adrenal metastasis; all were polysomic for chromosome
      7, none were amplified. No EGFR mutations have been found in the cerebral
      metastases. CONCLUSION: Because the molecular asset of EGFR may change during the
      metastatic progression of NSCLC to brain (but not to adrenal), the selection of
      patients with brain metastasis for specific targeted therapies by EGFR FISH
      analysis should be performed on metastatic lesions rather than on their
      corresponding primary tumors.

PMID- 19404217
TI  - Final overall results of a study with a novel triplet induction chemotherapy
      regimen (PACCAGE) followed by consolidation radiotherapy in locally advanced
      inoperable non-small cell lung cancer (NSCLC).
AB  - INTRODUCTION: We report the long term and overall results of a triplet induction
      chemotherapy regimen followed by standard radiotherapy in patients with locally
      advanced inoperable stage III non-small cell lung cancer. METHODS: Three cycles
      of paclitaxel, carboplatin, and gemcitabine were administered every 3 weeks
      before standard fractionated consolidation radiotherapy starting at least 4 weeks
      after the last chemotherapy administration. Toxicity and antitumor response was
      assessed in detail as well as the progression free and overall survival. RESULTS:
      Sixty-four patients (25 stage IIIA and 39 stage IIIB) received a total of 179
      cycles of chemotherapy. Fifty-six received the planned three cycles. Full-dose
      radiotherapy was administered in 47 patients (73%), a reduced dose in 11 (17%)
      and none in six (10%). A 55% objective response rate (OR) (one complete and 34
      partial responses) was observed after induction chemotherapy. After completing
      the whole treatment including radiotherapy, the OR was 40 of 47 evaluable
      patients (85%). Median time to progression was 10.9 month and median overall
      survival was 17.2 month, with a significant difference between stage IIIA and
      stage IIIB patients (23.4 versus 10.5 month; p = 0.011). The strongest predictor
      for a favorable long-term outcome was a metabolic complete response after
      chemotherapy. CONCLUSION: Induction chemotherapy with the paclitaxel,
      carboplatin, and gemcitabine regimen preceding radiotherapy in patients with
      locally advanced inoperable stage III non-small cell lung cancer was feasible and
      active. Radiotherapy could be administered at a full dose in the majority of
      patients with acceptable toxicity. Long-term survival results of this sequential
      chemoradiotherapy regimen appear similar to those of concurrent treatment.
      Patients not achieving a metabolic complete response after induction chemotherapy
      should be the focus of studies aiming at improved local control.

PMID- 19404218
TI  - The PI3-K/AKT-pathway and radiation resistance mechanisms in non-small cell lung
      cancer.
AB  - The phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (AKT) pathway is
      associated with all three major radiation resistance mechanisms: intrinsic
      radiosensitivity, tumor cell proliferation, and hypoxia. In cell signaling
      cascades, the PI3-K/AKT signaling pathway is a key regulator of normal and
      cancerous growth and cell fate decisions by processes such as proliferation,
      invasion, apoptosis, and induction of hypoxia-related proteins. Activation of
      this pathway can be the result of stimulation of receptor tyrosine kinases such
      as epidermal growth factor receptor or vascular endothelial growth factor
      receptor or from mutations or amplification of PI3-K or AKT itself which are
      frequently found in non-small cell lung cancer (NSCLC). Furthermore, several
      treatment modalities such as radiotherapy can stimulate this survival pathway.
      Monitoring and manipulation of this signal transduction pathway may have
      important implications for the management of NSCLC. Strong and independent
      associations were found between expression of activated AKT (pAKT) and treatment
      outcome in clinical trials. Direct targeting and inhibition of this pathway may
      increase radiosensitivity by antagonizing the radiation induced cellular defense
      mechanisms especially in tumors that have activated the PI3-K/AKT cascade. To
      successfully implement these treatments in daily practice, there is a need for
      molecular predictors of sensitivity to inhibitors of PI3-K/AKT activation. In
      conclusion, the PI3-K/AKT pathway plays a crucial role in cellular defense
      mechanisms. Therefore, quantification of the activation status is a potential
      parameter for predicting treatment outcome. More importantly, specific targeting
      of this pathway in combination with radiotherapy or chemotherapy may enhance
      tumor control in NSCLC by antagonizing cellular defense in response to treatment.

PMID- 19404219
TI  - Prediction of true positive lung cancers in individuals with abnormal suspicious
      chest radiographs: a prostate, lung, colorectal, and ovarian cancer screening
      trial study.
AB  - INTRODUCTION: Chest radiographs are routinely employed in clinical practice.
      Radiographic findings that are abnormal suspicious (AS) for lung cancer occur
      commonly. The majority of AS radiographic abnormalities are not cancer. This
      study identifies predictors of true positive (TP) AS and presents models for
      estimating the probability of lung cancer. METHODS: This is a prospective cohort
      study nested in the randomized National Cancer Institute's Prostate Lung
      Colorectal Ovarian Cancer Screening Trial (PLCO). First-time AS screens in the
      screening arm of the PLCO were studied. Associations between nonradiographic and
      radiographic factors, and TP AS were evaluated by multiple logistic regression.
      RESULTS: The PLCO intervention arm had 77,465 individuals, of whom 12,314 were AS
      and of these 232 (1.9%) had lung cancer (were TP). Important independent
      predictors of TP were older age, lower education, greater pack years and duration
      smoking history, body mass index <30, family history of lung cancer, lung nodule,
      lung mass, unilateral mediastinal or hilar lymphadenopathy, lung infiltrate, and
      upper/middle chest AS location. The model including these variables had a
      receiver operator characteristic area under the curve (ROC AUC) of 86.4%. This
      model excluding the smoking variables had an ROC AUC of 77.1% and excluding all
      nonradiographic variables had an ROC AUC of 73.3% (p < 0.0001 for all these model
      differences). Smoking and nonsmoking nonradiographic variables significantly
      added to prediction. CONCLUSION: This study identifies important nonradiographic
      and radiographic predictors of lung cancer, and presents an accurate model for
      estimating the probability of lung cancer in individuals with suspicious
      radiographs. These findings may be of value for screening, research, and patient
      and clinician decision-making.

PMID- 19404220
TI  - Electrophysiological evidence for a two-stage process underlying single chord
      priming.
AB  - In this study, we examine through electrophysiological measures three alternative
      mechanisms underlying musical chord priming: psychoacoustic distance, common
      parent-key, and distance along the circle of fifths. In contrast with previous
      behavioral studies, we present complex tones which do not blur the melodic
      component, we present various chord arrangements, and we focus on nonmusicians.
      Target major chords, in three different harmonic conditions (1, 2, and 4 steps
      along the circle of fifths between prime and target chords), elicited two centro
      anterior negativities labeled N5E (early) and N5L (late) suggesting a
      dissociation between an earlier psychoacoustic process based on pitch commonality
      and proximity and a later cognitive process based on a common parent-key.

PMID- 19404221
TI  - Reducing cycle times in pediatric emergency medicine.
AB  - OBJECTIVE: Reducing cycle times in pediatric emergency medicine is an ongoing
      challenge to practitioners and institutions who strive to provide outstanding
      medical care in a caring and efficient manner amid the chaotic environment of a
      busy emergency department. For institutions that wish to undertake such a task,
      there is scant pediatric literature on these topics. The objectives of this study
      were to reduce emergency department cycle times and to set a benchmark in these
      areas for pediatric emergency medicine. METHODS: After the implementation of
      interventions to promote efficiency, goals were chosen in 2 areas: operational
      and clinical cycle time reductions. The goals were set for 1 year and then
      followed longitudinally for an additional 4 years to evaluate sustainability of
      results. For the first year, the operational goal for the emergency center (EC)
      was to reduce the time in department (TID) from 3 hours 6 minutes to 2 hours 50
      minutes, representing a 9% decrease. The corresponding goal in quick kid (QK) was
      to reduce the TID from 1 hour 35 minutes to 1 hour 15 minutes, representing a 21%
      decrease. The clinical goal for both the EC and QK was to reduce the time to
      initial administration of pain medications for suspected extremity fractures from
      1 hour 42 minutes to 30 minutes, representing a 71% decrease. RESULTS: During the
      initial year of the study, the mean time in the EC decreased by 9%, whereas in
      QK, the mean TID decreased by 16%. The time to administration of pain medications
      for patients with suspected fracture decreased by 58%. Longitudinal analysis
      revealed sustainability of in all areas studied. CONCLUSIONS: At 1 year, we were
      able to reduce cycle times in the main EC and QK and time of pain medication
      administration for patients with suspected fractures. These results were
      sustainable over time and in the face of increasing patient volume. We anticipate
      this work will set benchmarks in pediatric emergency medicine for process
      improvement and support the development of similar programs to reduce cycle times
      and improve operational efficiency.

PMID- 19404222
TI  - Use of the pediatric EZ-IO needle by emergency medical services providers.
AB  - OBJECTIVE: The aim of this study was to examine emergency medical services
      providers' use of a new intraosseous needle designed for pediatric patients.
      METHODS: This prospective pilot study was conducted between May 2006 and October
      2007. After completing an initial training session, the EZ-IO PD was deployed for
      use on patients. Emergency medical services (EMS) providers completed a telephone
      data collection process after each insertion attempt. Data regarding insertion
      failure or success (insertion of needle into the bone with subsequent fluid
      flow), time to fluid flow, provider comfort with the device, device performance
      assessment, and recommendation for future use were collected. RESULTS: Two
      hundred forty-six EMS providers (EMT-P and registered nurses) from 14 EMS
      agencies consented to participation. Nineteen insertions were completed by 19
      different providers during the study period. Successful insertion was achieved in
      18 (95%) of 19 patients (95% confidence interval [CI], 85%-100%). Successful
      insertion was achieved in less than 60 seconds by 13 (72%) of 15 providers (95%
      CI, 60%-94%; 4 providers, no response). Fourteen out of 17 providers (82%)
      reported feeling very comfortable (59%) or comfortable (23%) with the device (95%
      CI, 64%-100%; 2 non-responses). Fourteen (82%) of 17 providers (95% CI, 64%-100%)
      with a successful insertion felt that the device worked very well, and the
      remaining 3 (18%) felt that it worked well. Thirteen (78%) of 17 providers (95%
      CI, 56%-96%) recommended future use of the EZ-IO needle over the Illinois needle.
      Two providers (11%) recommended the use of both needles, and 2 providers (11%)
      were unsure if they would recommend one of the intraosseous needles over the
      other. A total of 5 complications were reported by the providers: infiltration
      during use (2); slow flow rate (2); and needle dislodgement (1) when moving the
      patient into the ambulance. CONCLUSIONS: This device has a high insertion success
      rate with our provider group. Most of our EMS providers also felt comfortable
      using the device and recommend the device for future use.

PMID- 19404223
TI  - Serious adverse events during procedural sedation with ketamine.
AB  - OBJECTIVES: Compare the frequency of respiratory adverse events between patients
      who received intramuscular (IM) versus intravenous ketamine. METHODS: Case
      control study from 1997 to 2005 at a large urban pediatric emergency department.
      Adverse events were defined as apnea, hypoxemia (oximetry <93%), hypoventilation,
      laryngospasm, and other upper airway obstruction. Serious adverse events were
      defined by the level of intervention and included those cases that required
      positive pressure ventilation, insertion of oral or nasal airway, or endotracheal
      intubation. Minor adverse events were respiratory events requiring minimal
      intervention (stimulation, supplemental O2, airway repositioning). Controls (2:1)
      were selected by the next chronological patient in the data set who received
      ketamine but had no respiratory adverse event. RESULTS: Four thousand two hundred
      fifty-two patients received ketamine; 102 cases (2.4%) had respiratory adverse
      events, including 38 patients with severe adverse events (0.9%). Interventions
      for the cases included supplemental O2 (59/102, 58%), airway repositioning
      (36/102, 35%), continuous positive airway pressure (7/102, 7%), positive pressure
      ventilation (33/102, 32%), nasal airway (2/102, 2%), oral airway (1/102, 1%),
      stimulation (11/102, 11%), and intubation (1/102, 1%). Overall, 33% of all
      subjects received IM ketamine including 47% of cases and 27% of controls.
      Intramuscular IM ketamine was associated with increased likelihood of adverse
      events (odds ratio [OR] 2.1, 95% CI, 1.3-3). Twenty (69%) of the 29 patients with
      laryngospasm received IM ketamine (OR, 5.2; 95% CI, 2.3-11.9) and 20 (53%) of the
      38 patients who had severe events were administered IM (OR, 2.4; 95% CI, 1.2
      4.9). Use of pre-sedation morphine or combined administration with midazolam
      and/or atropine was not associated with adverse events. Specific procedures were
      not associated with increased adverse events. CONCLUSIONS: Respiratory adverse
      events with ketamine are uncommon. Serious events, like laryngospasm, are rare
      but occur more commonly with IM administration. This increased risk associated
      with IM administration should be considered in the sedation plan.

PMID- 19404224
TI  - Evaluating the injury incidence from skate shoes in the United States.
AB  - OBJECTIVES: The goals of this study were to evaluate whether the increased use of
      skate shoes may lead to an increase in injuries for children and adolescents aged
      5 to 14 years in the United States and to describe the types of injuries reported
      by emergency departments as a result of skate shoe use. METHODS: Retrospective
      analysis of the National Electronic Injury Surveillance System database from
      January 1, 2002 to December 31, 2006 for injuries resulting from footwear in
      children and adolescents aged 5 to 14 years. Injuries resulting from skate shoe
      use were identified by manual review of the data. RESULTS: For the 5-year period,
      an estimated 3525 patients between 5 and 14 years of age were treated in United
      States emergency departments for injuries resulting from skate shoe use. The
      percentage of injuries resulting from skate shoes of total footwear-related
      injuries varied by year, however, with 1.0%, 1.0%, 0.8%, and 1.9% occurring in
      2002 to 2005, respectively, and 11.8% occurring in 2006. This substantial
      increase in 2006 accounts for 73.6% of skate shoe-related injuries and is
      statistically significant (chi, P = <0.0001). This rising trend in 2006
      paralleled national skate shoe sales, with a correlation coefficient of
      0.9982.Most of the injured children and adolescents were white, and there was a
      slight, nonsignificant predominance of boys. Most injuries in all 5-year-olds
      were fractures (46.7%), followed by contusions (17.9%) and sprains (17.2%). The
      most frequent site of fracture was the forearm (38.4%), followed by the wrist
      (35.1%) and the leg (14.9%). Other injuries included lacerations (7.3%),
      concussions (6.6%), internal organ injuries (0.9%), hematomas (0.2%),
      dislocations (0.2%), and injuries not otherwise specified (3.1%). Based on
      national estimates, 104 (0.01%) patients required admission to the hospital. No
      injuries recorded in the National Electronic Injury Surveillance System database
      resulted in death. CONCLUSIONS: As the first study analyzing injury rates as a
      result of skate shoe use in the United States, this study demonstrated a recent
      increase in injuries to children and adolescents using skate shoes, which
      paralleled the products' sales increase. The types of injuries are primarily a
      wide range of non-life threatening bone and soft tissue injuries.

PMID- 19404226
TI  - Do all pediatric patients who have a febrile seizure require transport by
      advanced life support?
AB  - OBJECTIVE: In the state of New Jersey, all pediatric patients who are transported
      to the hospital by emergency medical services for seizures are evaluated by both
      advanced life support (ALS) and basic life support (BLS) units. The state triage
      protocol mandates that a paramedic unit be dispatched. The purpose of this study
      is establish that the subset of those patients who experience simple febrile
      seizures could be safely transported by BLS, subsequently freeing much needed ALS
      resources. METHODS: This study was performed using a retrospective chart review.
      Seventy-one consecutive patients who experienced febrile seizures and were
      transported to the Bristol-Meyers-Squib Children's Hospital/Robert Wood Johnson
      University Hospital via ALS were included. These patients were risk stratified
      into groups which were analyzed for interventions, including inpatient admission,
      medication delivery, intubation, or respiratory support. RESULTS: From this
      analysis, we are identified factors in the history and physical examination of
      patients in the field that would help to classify the patient as having a "simple
      febrile seizure" and thus significantly lowering the risk of any potential
      negative outcome. CONCLUSIONS: Simple febrile seizure patients are suitable for
      transport via BLS. Further studies should be done to confirm this conclusion.

PMID- 19404225
TI  - Epidemiology of admissions in a pediatric resuscitation room.
AB  - OBJECTIVE: Describe the epidemiology of a pediatric resuscitation room (PRR).
      METHODS: A prospective study was performed in a pediatric emergency department
      (PED) from June 17, 2004 to March 19, 2006. Collected data were date and time of
      admission in the unit and, in the PRR, age and sex, geographical origin, mode of
      transportation, PED referral mode, diagnosis, evolution, and resuscitation
      techniques. Statistical analysis included a univariate analysis of hypothetical
      links between variables and their relation to the risk of death or transfer to
      the pediatric intensive care unit, then a multivariate analysis by logistical
      regression where the dependant variable was this risk. RESULTS: Three hundred
      sixty-one patients totaled 370 admissions. The male-female ratio was 1.3. Mean
      (SD) age was 5.5 (5.2) years. A quarter of the population was recommended for
      admission by a physician. Main causes were cardiocirculatory (32%), neurological
      (26%), respiratory (23%), and traumas (18%), and 17% were hospitalized in an
      intensive care unit and 4 died. Sixteen technical resuscitation procedures were
      performed. Children from 0 to 2 years old were more often admitted for
      cardiocirculatory insufficiency (P < 0.001). The children who were at higher risk
      for pediatric intensive care unit transfer or death were children from 0 to 2
      years old (P < 0.001), an admission for respiratory insufficiency (P < 0.001),
      and an arrival by medicalized transport (P = 0.003). CONCLUSIONS: In addition to
      national guidelines for PRR management, the teaching and knowledge of the
      different diagnosis admitted in the PRR and their resuscitation technical
      procedures warranty a serener approach of those stressful situations.

PMID- 19404227
TI  - Final evaluation of the 2005 to 2007 National Pediatric Emergency Medicine
      Fellows' Conferences.
AB  - OBJECTIVE: Evaluate the effectiveness of the 2005 to 2007 National Pediatric
      Emergency Medicine (PEM) Fellows Conference series in achieving predefined
      objectives in the domains of scholarship, leadership, and partnership. METHODS:
      Conference attendees included fellows in the existing PEM fellowship programs.
      Self-administered preconference and postconference questionnaires measured
      knowledge, research-related confidence, beliefs about institutional support for
      Emergency Medical Services for Children (EMSC) research, and intentions to engage
      in 7 specific behaviors relating to scholarship, leadership, and partnership.
      Pearson product-moment correlations measured relationships among continuous
      variables. Repeated-measures analysis of variance measured change between
      preconference and postconference measures. Hierarchical multiple linear
      regression models identified predictors of postconference intentions to engage in
      each of the 7 specific behaviors, controlling for preconference intention.
      RESULTS: Approximately one third of all PEM fellows attended the conference each
      year. Preconference and postconference questionnaires were completed by at least
      70% of attendees each year. Because several fellows attended more than one
      conference, data were analyzed from the first conference that a fellow attended.
      In each year, we observed significant increases in attendees' conference-specific
      knowledge, confidence, and intentions to continue in EMSC research, join national
      collaborative research networks, and establish national mentoring relationships.
      CONCLUSIONS: The National PEM Fellows' Conference is an effective means to
      increasing fellows' knowledge about scholarship, leadership, and partnership in
      EMSC and increasing their confidence and intentions to conduct research in EMSC.

PMID- 19404228
TI  - Parental preference for rehydration method for children in the emergency
      department.
AB  - OBJECTIVE: To determine which rehydration method, oral or intravenous, parents
      would choose for their child when given the opportunity to make an informed
      decision and to determine factors influencing preference. METHODS: Parents of
      children, aged 6 months to 5 years, who presented to a pediatric emergency
      department with a chief complaint of vomiting and/or diarrhea were eligible.
      After triage evaluation and before physician assessment, research assistants
      presented educational materials regarding the method, risks, and benefits of both
      oral and intravenous rehydration. Parents were then asked to complete a survey
      asking them their preference, reasons for their preference, questions about their
      child's current illness, and demographic information. RESULTS: Two hundred sixty
      parents completed the study. Ninety eight (38%) preferred oral rehydration, and
      162 (62%) preferred intravenous rehydration. Time of day, presence of siblings in
      the ED requiring parental attention, presence of another adult to provide
      support, parental age, educational attainment, and employment status were not
      statistically associated with the stated preference. Of those parents who
      selected intravenous rehydration, 53% stated that they would choose oral
      rehydration if there was an oral medication available that would significantly
      decrease vomiting. Of those parents who selected oral rehydration, 32% stated
      that they would choose intravenous rehydration if there was a topical medication
      available that would significantly decrease the pain of intravenous catheter
      placement. CONCLUSIONS: When given the opportunity to make an informed decision,
      more parents chose intravenous rehydration. However, the prospect of an effective
      oral antiemetic medication might lead more parents to choose oral rehydration.

PMID- 19404229
TI  - Children born small for gestational age: multidisciplinary approach.
AB  - The definition of a newborn SGA changes depending on which parameter is taken as
      reference. For the neonatologists who are the first to take care of these
      newborns the most used parameter in the past has been the weight that should be
      below the 10 centile for the reference standards. In the last years paediatric
      endocrinologists are more and more interested in the length of these newborns, a
      parameter more accurate to growth. This paper presents the last consensus
      statements regarding the definition of SGA newborns taken into consideration the
      length, the weight, both or them and even the head circumference.

PMID- 19404230
TI  - Intrauterine growth retardation (IUGR): prenatal diagnosis by imaging.
AB  - The early detection of the IUGR is of great importance. The ultrasounds technique
      is the gold standard to estimate the foetal size. The combination of some
      biochemical markers and uterine doppler opens a promising way for an early
      identification of the IUGR. The estimated foetal weight or the abdominal
      circumference combined with a doppler of the umbilical artery seems to be the
      most sensitive and specific method to diagnose a pathological growth retardation
      due to a foetal placental disfunction. The umbilical doppler and also of the
      cerebral arteries and the venous doppler besides the biophysical procedures, have
      to be used to plan the optimal moment for the delivery.

PMID- 19404231
TI  - Intrauterine growth retardation (IUGR): epidemiology and etiology.
AB  - Intrauterine growth retardation (IUGR) is mainly due to a pathologic slow-down in
      the fetal growth pace, resulting in a fetus that is unable to reach its growth
      potential. IUGR frequency will vary depending on the discrimination criteria
      adopted. It is extremely important to use local or national fetal growth graphs
      in order to avoid some confounding factors. IUGR incidence in newborns would be
      between 3% and 7% of the total population. In our experience it is 5.13% a figure
      similar to the one obtained by other authors but with a progressively higher
      incidence during the last decade. There are multiple maternal factors that can
      generally be grouped into constitutional and general factors given that they
      affect age, weight, race, maternal cardiac volume, etc, socioeconomic factors
      with key incidence in the mother's nutrition level, where a poor maternal
      nutrition level would be the key factor in this group. We have evaluated multiple
      factors as possible contributors to the IUGR risk: race, parents' age, mother's
      height (cm), mother's birth weight and before pregnancy (kg), ponderal gain and
      blood pressure during pregnancy, and previous SGA newborns. Socioeconomic factors
      like social class, parents' profession, habitual residence, salary, immigration,
      and diet were also evaluated. We also included variables such as total daily
      working time and time mothers spent standing up, daily sleeping time (hrs),
      stress self-perception test at work and primiparity age. Toxic factors during
      pregnancy: tobacco (active and passive), alcohol, drugs and coffee consumption.
      Fetal or utero-placental factors were considered. In our study, the most
      significant etiologic factors were: Active and passive tobacco consuming,
      mother's stress level, increase of total months worked during pregnancy, total
      daily working hours and time mothers spent standing up and finally, the parent's
      height. Our data support the main objective of reducing the incidence of SGA
      newborns after IUGR by fighting against tobacco from all fields, including the
      passive smoking habit, and improving the laboral conditions of the pregnant
      mother, lowering the number of daily hours worked, the physical activity and
      trying to avoid and to cope with stressful situations.

PMID- 19404232
TI  - Study of apoptosis and related proteins, CRH and hpGH in placentas of newborns
      small for gestational age (SGA).
AB  - The aim of this study is to quantify the expression of apoptotic genes and genes
      related to the development and growth in placentas of pregnancies with IUGR
      (intrauterine growth restriction) and normal placentas. We studied the expression
      of Bcl-2, Caspase3, hpGH (human placental growth hormone) and CRH (corticotropin
      releasing hormone) genes in normal and IUGR placentas. In addition we have
      demonstrated this expression by immunohistochemical techniques. MATERIAL AND
      METHODS: Placentas of newborns with intrauterine infections, complicated
      pregnancies, congenital malformations and birth asphyxia were excluded. RNA
      extraction and purification. Total RNA was extracted and cleansed from the lysate
      using RNA wiz (Ambion) and Qiagen Rneasy Mini (Qiagen). cDNA synthesis. This
      assay was performed using the Retroscript Kit, Ambion. RT-PCR was performed with
      the LightCycler System 2.0 (Roche Diagnostics) and the LightCycler FastStart DNA
      Master Plus SYBR Green I. An immunochemical study was performed using the
      Envision Plus Dako protocol. RESULTS: Bcl-2, hpGH and CRH are down regulated in
      the SGA group in comparison to the control group. Caspase3 is up regulated in the
      SGA group in comparison to the control group. We demonstrated that in placentas
      from pregnancies with IUGR, expression of Bcl-2is diminished and expression of
      caspase 3 is augmented compared to normal placentas.

PMID- 19404233
TI  - Study of early detection of cardiovascular risk factors in children born small
      (SGA) and review of literature.
AB  - Many children are born small for gestational age (SGA), due to intrauterine
      growth retardation (IUGR) and in recent years we have witnessed an increase in
      the prevalence of this problem. In our region, Aragon, 5% of children (between
      550-600 per year) are born SGA, which represents a serious public health problem.
      Some studies have suggested that these patients have a higher risk of suffering
      from high blood pressure (HBP), dyslipidemia, obesity, insulin resistant diabetes
      and atherosclerosis in adulthood. Nevertheless other publications do not support
      this hypothesis, so given the lack of consensus on the potential risks of this
      situation, we believed it would be interesting to study, at an early stage of
      life, whether a sample of children born SGA would present greater cardiovascular
      risk factors than children born with an adequate weight for gestational age
      (AGA).

PMID- 19404234
TI  - Growth and growth hormone treatment in short stature children born small for
      gestational age.
AB  - Persistent short stature is one of the most frequent complications of being born
      small for gestational age (SGA) as almost 15% of such children have a low adult
      height. Additionally, individuals born SGA may have low lean body mass and
      increased central adiposity which put them at risk of long-term morbidity related
      to insulin resistance and metabolic disease. Onset of puberty appears at a normal
      age but comes relatively early for their actual height. There are studies that
      show that the pubertal growth spurt is moderately decreased in SGA and some girls
      may experience advanced pubarche and menarche. We have retrospectively analyzed
      64 untreated SGA children and we have observed that adult height was lower than
      target height and positively correlated with maternal height, target height and
      height at onset of puberty; the tempo of puberty was very similar between SGA and
      controls but pubertal growth spurt was lower in SGA than in controls. The
      pathophysiology of postnatal growth failure is complex and different anomalies in
      the GH-IGF axis had been described. The effect of GH therapy on linear growth and
      adult height has been extensively studied in the last 15 years. In the short
      term, GH treatment produces an acceleration of growth with a significant
      increment of height which is dose dependent during the first 3-4 years. The long
      term response is less dose dependent and the vast majority of short SGA children
      reach an adult height within normal standards and adequate for their target
      height. There is an important variation in the growth response of SGA children to
      GH indicating that SGA represents a heterogeneous condition in which response
      during the first year is the most important predictor of subsequent growth
      response. GH appears to be safe at the current doses employed but monitoring of
      IGF-I, IGFBP-3 and glucose metabolism is mandatory during therapy.

PMID- 19404235
TI  - Psychomotor and intellectual development (Neurocognitive Function) of children
      born small for gestational age (SGA). Transversal and longitudinal study.
AB  - Although much is now known about the effects of intrauterine growth retardation
      (IUGR) on children born SGA with regard to anthropometric and biochemical
      parameters and their treatment, there are still many gaps associated with its
      impact on neurocognitive functions. In our experience published several years
      ago, IUGR has a negative effect on neurocognitive development, regardless of
      whether these children showed evidence of catch-up growth or not or of the socio
      economic conditions that might contribute to the situation. We have now
      accumulated a large number of cases, many of whom have been followed
      longitudinally, some for up to 7 years, many having been treated with GH from the
      time when this therapy was first approved by the EMA. Apart from the cases
      mentioned, other confounding factors such as gestational age, Apgar score,
      neonatal comorbidity and the possible effects of GH treatment have also been
      included. In addition and using our own reference standards, we now present our
      experience, which confirms what we had already noted in the past, that IUGR is in
      itself a condition that often causes psychomotorintellectual impairment, may be
      extremely severe and tends to worsen. This negative impact of IUGR on
      neurocognitive development does not depend on how the child grows,spontaneous
      growth is better and when growth is not altered by GH therapy. Later studies will
      be able to confirm whether early treatment with GH throughout the 2nd year of
      life, or an early specific stimulation programme, or the sum of both, can improve
      the neurocognitive development of these children. IUGR prevention, acting on
      causal factors that are partly avoidable such as smoking, working conditions and
      stress during pregnancy (see the corresponding article in this supplement) proves
      once again to be the best way to stop this negative impact on the IQ of many
      children born SGA.

PMID- 19404236
TI  - In vivo bioluminescent imaging of mammary tumors using IVIS spectrum.
AB  - 4T1 mouse mammary tumor cells can be implanted sub-cutaneously in nu/nu mice to
      form palpable tumors in 15 to 20 days. This xenograft tumor model system is
      valuable for the pre-clinical in vivo evaluation of putative antitumor compounds.
      The 4T1 cell line has been engineered to constitutively express the firefly
      luciferase gene (luc2). When mice carrying 4T1-luc2 tumors are injected with
      Luciferin the tumors emit a visual light signal that can be monitored using a
      sensitive optical imaging system like the IVIS Spectrum. The photon flux from the
      tumor is proportional to the number of light emitting cells and the signal can be
      measured to monitor tumor growth and development. IVIS is calibrated to enable
      absolute quantitation of the bioluminescent signal and longitudinal studies can
      be performed over many months and over several orders of signal magnitude without
      compromising the quantitative result. Tumor growth can be monitored for several
      days by bioluminescence before the tumor size becomes palpable or measurable by
      traditional physical means. This rapid monitoring can provide insight into early
      events in tumor development or lead to shorter experimental procedures. Tumor
      cell death and necrosis due to hypoxia or drug treatment is indicated early by a
      reduction in the bioluminescent signal. This cell death might not be accompanied
      by a reduction in tumor size as measured by physical means. The ability to see
      early events in tumor necrosis has significant impact on the selection and
      development of therapeutic agents. Quantitative imaging of tumor growth using
      IVIS provides precise quantitation and accelerates the experimental process to
      generate results.

PMID- 19404237
TI  - An optical cloak made of dielectrics.
AB  - Invisibility devices have captured the human imagination for many years. Recent
      theories have proposed schemes for cloaking devices using transformation optics
      and conformal mapping. Metamaterials, with spatially tailored properties, have
      provided the necessary medium by enabling precise control over the flow of
      electromagnetic waves. Using metamaterials, the first microwave cloaking has been
      achieved but the realization of cloaking at optical frequencies, a key step
      towards achieving actual invisibility, has remained elusive. Here, we report the
      first experimental demonstration of optical cloaking. The optical 'carpet' cloak
      is designed using quasi-conformal mapping to conceal an object that is placed
      under a curved reflecting surface by imitating the reflection of a flat surface.
      The cloak consists only of isotropic dielectric materials, which enables
      broadband and low-loss invisibility at a wavelength range of 1,400-1,800 nm.

PMID- 19404238
TI  - Controlling interpenetration in metal-organic frameworks by liquid-phase epitaxy.
AB  - Metal-organic frameworks (MOFs) are highly porous materials generally consisting
      of two building elements: inorganic coupling units and organic linkers. These
      frameworks offer an enormous porosity, which can be used to store large amounts
      of gases and, as demonstrated in more recent applications, makes these compounds
      suitable for drug release. The huge sizes of the pores inside MOFs, however, also
      give rise to a fundamental complication, namely the formation of sublattices
      occupying the same space. This interpenetration greatly reduces the pore size and
      thus the available space within the MOF structure. We demonstrate here that the
      formation of the second, interpenetrated framework can be suppressed by using
      liquid-phase epitaxy on an organic template. This success demonstrates the
      potential of the step-by-step method to synthesize new classes of MOFs not
      accessible by conventional solvothermal methods.

PMID- 19404240
TI  - Similarities between structural distortions under pressure and chemical doping in
      superconducting BaFe2As2.
AB  - The discovery of a new family of high-T(C) materials, the iron arsenides (FeAs),
      has led to a resurgence of interest in superconductivity. Several important
      traits of these materials are now apparent: for example, layers of iron
      tetrahedrally coordinated by arsenic are crucial structural ingredients. It is
      also now well established that the parent non-superconducting phases are
      itinerant magnets, and that superconductivity can be induced by either chemical
      substitution or application of pressure, in sharp contrast to the cuprate family
      of materials. The structure and properties of chemically substituted samples are
      known to be intimately linked; however, remarkably little is known about this
      relationship when high pressure is used to induce superconductivity in undoped
      compounds. Here we show that the key structural features in BaFe2As2, namely
      suppression of the tetragonal-to-orthorhombic phase transition and reduction in
      the As-Fe-As bond angle and Fe-Fe distance, show the same behaviour under
      pressure as found in chemically substituted samples. Using experimentally derived
      structural data, we show that the electronic structure evolves similarly in both
      cases. These results suggest that modification of the Fermi surface by structural
      distortions is more important than charge doping for inducing superconductivity
      in BaFe2As2.

PMID- 19404239
TI  - Intravaginal gene silencing using biodegradable polymer nanoparticles densely
      loaded with small-interfering RNA.
AB  - Vaginal instillation of small-interfering RNA (siRNA) using liposomes has led to
      silencing of endogenous genes in the genital tract and protection against
      challenge from infectious disease. Although siRNA lipoplexes are easily
      formulated, several of the most effective transfection agents available
      commercially may be toxic to the mucosal epithelia and none are able to provide
      controlled or sustained release. Here, we demonstrate an alternative approach
      using nanoparticles composed entirely of FDA-approved materials. To render these
      materials effective for gene silencing, we developed novel approaches to load
      them with high amounts of siRNA. A single dose of siRNA-loaded nanoparticles to
      the mouse female reproductive tract caused efficient and sustained gene
      silencing. Knockdown of gene expression was observed proximal (in the vaginal
      lumen) and distal (in the uterine horns) to the site of topical delivery. In
      addition, nanoparticles penetrated deep into the epithelial tissue. This is the
      first report demonstrating that biodegradable polymer nanoparticles are effective
      delivery vehicles for siRNA to the vaginal mucosa.

PMID- 19404241
TI  - Free-standing nanoparticle superlattice sheets controlled by DNA.
AB  - Free-standing nanoparticle superlattices (suspended highly ordered nanoparticle
      arrays) are ideal for designing metamaterials and nanodevices free of substrate
      induced electromagnetic interference. Here, we report on the first DNA-based
      route towards monolayered free-standing nanoparticle superlattices. In an
      unconventional way, DNA was used as a 'dry ligand' in a microhole-confined,
      drying-mediated self-assembly process. Without the requirement of specific Watson
      Crick base-pairing, we obtained discrete, free-standing superlattice sheets in
      which both structure (inter-particle spacings) and functional properties
      (plasmonic and mechanical) can be rationally controlled by adjusting DNA length.
      In particular, the edge-to-edge inter-particle spacing for monolayered
      superlattice sheets can be tuned up to 20 nm, which is a much wider range than
      has been achieved with alkyl molecular ligands. Our method opens a simple yet
      efficient avenue towards the assembly of artificial nanoparticle solids in their
      ultimate thickness limit--a promising step that may enable the integration of
      free-standing superlattices into solid-state nanodevices.

PMID- 19404243
TI  - Altered M(1) muscarinic acetylcholine receptor (CHRM1)-Galpha(q/11) coupling in a
      schizophrenia endophenotype.
AB  - Alterations in muscarinic acetylcholine receptor (CHRM) populations have been
      implicated in the pathology of schizophrenia. Here we have assessed whether the
      receptor function of the M(1) subtype (CHRM1) is altered in a sub-population of
      patients with schizophrenia, defined by marked (60-80%) reductions in cortical
      [3H]-pirenzepine (PZP) binding, and termed 'muscarinic receptor-deficit
      schizophrenia' (MRDS). Using a [35S]-GTPgammaS-Galpha(q/11) immunocapture method
      we have assessed whether CHRM1 signalling in human cortex (Brodmann area 9 (BA9))
      is altered in post mortem tissue from a MRDS group compared with a subgroup of
      patients with schizophrenia displaying normal PZP binding, and controls with no
      known history of psychiatric or neurological disorders. The CHRM agonist
      (oxotremorine-M) and a CHRM1-selective agonist (AC-42) increased Galpha(q/11)
      [35S]-GTPgammaS binding, with AC-42 producing responses that were approximately
      50% of those maximally evoked by the full agonist, oxotremorine-M, in control and
      subgroups of patients with schizophrenia. However, the potency of oxotremorine-M
      to stimulate Galpha(q/11)-[35S]-GTPgammaS binding was significantly decreased in
      the MRDS group (pEC(50) (M)=5.69+/-0.16) compared with the control group (6.17+/
      0.10) and the non-MRDS group (6.05+/-0.07). The levels of Galpha(q/11) protein
      present in BA9 did not vary with diagnosis. Maximal oxotremorine-M-stimulated
      Galpha(q/11)-[35S]-GTPgammaS binding in BA9 membranes was significantly increased
      in the MRDS group compared with the control group. Similar, though non
      statistically significant, trends were observed for AC-42. These data provide
      evidence that both orthosterically and allosterically acting CHRM agonists can
      stimulate a receptor-driven functional response ([35S]-GTPgammaS binding to
      Galpha(q/11)) in membranes prepared from post mortem human dorsolateral
      prefrontal cortex of patients with schizophrenia and controls . Furthermore, in a
      subgroup of patients with schizophrenia displaying markedly decreased PZP binding
      (MRDS) we have shown that although agonist potency may decrease, the efficacy of
      CHRM1-Galpha(q/11) coupling increases, suggesting an adaptative change in
      receptor-G protein coupling efficiency in this endophenotype of patients with
      schizophrenia.

PMID- 19404244
TI  - Clomipramine and glucocorticoid receptor function.

PMID- 19404245
TI  - Mucosal immunology of geohelminth infections in humans.
AB  - There is limited data on the human mucosal immune response to geohelminths, but
      extensive data from experimental animals. Geohelminth infections may modulate
      mucosal immunity with effects on parasite expulsion or persistence and mucosal
      inflammation. Geohelminths are considered to have important effects on immunity
      to mucosal vaccines, infectious disease susceptibility, and anti-inflammatory
      effects in inflammatory bowel disease and asthma. This review will discuss the
      findings of studies of human immunity to geohelminths and their potential effects
      on non-parasite mucosal immune responses. Such effects are likely to be of public
      health importance in middle- and low-income countries where these parasites are
      endemic. There is a need for human studies on the effects of geohelminth
      infections on mucosal immunity and the potential for anthelmintic treatment to
      modify these effects. Such studies are likely to provide important insights into
      the regulation of mucosal immunity and inflammation, and the development of more
      effective mucosal vaccines.

PMID- 19404242
TI  - The hippocampus and cingulate cortex differentially mediate the effects of
      nicotine on learning versus on ethanol-induced learning deficits through
      different effects at nicotinic receptors.
AB  - The current study examined the effects of nicotine infusion into the dorsal
      hippocampus or anterior cingulate on fear conditioning and on ethanol-induced
      deficits in fear conditioning, and whether these effects involved receptor
      activation or inactivation. Conditioning consisted of two white noise (30 s, 85
      dB)-foot-shock (2 s, 0.57 mA) pairings. Saline or ethanol was administered to
      C57BL/6 mice 15 min before training and saline or nicotine was administered 5 min
      before training or before training and testing. The ability of the high-affinity
      nicotinic acetylcholinergic receptor (nAChR) antagonist dihydro-beta-erythroidine
      (DHbetaE) to modulate the effects of ethanol and nicotine was also tested; saline
      or DHbetaE was administered 25 (injection) or 15 (infusion) minutes before
      training or before training and testing. Infusion of nicotine into the
      hippocampus enhanced contextual fear conditioning but had no effect on ethanol
      induced learning deficits. Infusion of nicotine into the anterior cingulate
      ameliorated ethanol-induced deficits in contextual and cued fear conditioning but
      had no effect on learning in ethanol-naive mice. DHbetaE blocked the effects of
      nicotine on ethanol-induced deficits; interestingly, DHbetaE alone and co
      administration of subthreshold doses of DHbetaE and nicotine also ameliorated
      ethanol-induced deficits but failed to enhance learning. Finally, DHbetaE failed
      to ameliorate ethanol-induced deficits in beta2 nAChR subunit knockout mice.
      These results suggest that nicotine acts in the hippocampus to enhance contextual
      learning, but acts in the cingulate to ameliorate ethanol-induced learning
      deficits through inactivation of high-affinity beta2 subunit-containing nAChRs.

PMID- 19404246
TI  - Cholera toxin B suppresses allergic inflammation through induction of secretory
      IgA.
AB  - In healthy individuals, humoral immune responses to allergens consist of serum
      IgA and IgG4, whereas cellular immune responses are controlled by regulatory T
      (Treg) cells. In search of new compounds that might prevent the onset of
      allergies by stimulating this type of immune response, we have focused on the
      mucosal adjuvant, cholera toxin B (CTB), as it induces the formation of Treg
      cells and production of IgA. Here, we have found that CTB suppresses the
      potential of dendritic cells to prime for Th2 responses to inhaled allergen. When
      we administered CTB to the airways of naive and allergic mice, it strongly
      suppressed the salient features of asthma, such as airway eosinophilia, Th2
      cytokine synthesis, and bronchial hyperreactivity. This beneficial effect was
      only transferable to other mice by transfer of B but not of T lymphocytes. CTB
      caused a transforming growth factor-beta-dependent rise in antigen-specific IgA
      in the airway luminal secretions, which was necessary for its preventive and
      curative effect, as all effects of CTB were abrogated in mice lacking the luminal
      IgA transporting polymeric Ig receptor. Not only do these findings show a novel
      therapeutic avenue for allergy, they also help to explain the complex
      relationship between IgA levels and risk of developing allergy in humans.

PMID- 19404247
TI  - The global portfolio of new antimalarial medicines under development.
AB  - With the elimination of malaria now considered a realistic goal, it would be
      useful for scientists and policy makers to have an inventory of the arsenal of
      antimalarials, current and prospective, that could help make this goal a reality.
      In order to provide an overview of antimalarial projects in recent clinical
      development, we review here the global portfolio of antimalarial drugs in
      clinical phases of development complemented by projects in the preclinical and
      early discovery phases. The portfolio is discussed in terms of the novelty of the
      new molecules and their potential health impact in terms of addressing the
      requirements for the control and eventual eradication of malaria.

PMID- 19404248
TI  - Pretransplant pharmacodynamic analysis of immunosuppressive agents using CFSE
      based T-cell proliferation assay.
AB  - The impact of pretransplant T-cell sensitivity testing using carboxylfluorescein
      diacetate succinimidyl ester (CFSE)-based flow cytometry was studied in 32
      patients with chronic renal failure. There was considerable interindividual
      variation in the inhibitory effects of cyclosporine (CSA), tacrolimus (TAC), and
      prednisolone (PRD) but only a small amount of interindividual variation for
      mycophenolic acid (MPA). Patients with high sensitivity to CSA tended to
      experience viral reactivation. In addition to post-transplant blood-level
      monitoring, pretransplant pharmacodynamics could provide useful information on
      optimal and safe immunosuppressive therapy.

PMID- 19404249
TI  - Thinking about broadly cross-reactive vaccines.

PMID- 19404250
TI  - Lifeact cannot visualize some forms of stress-induced twisted F-actin.

PMID- 19404251
TI  - Without a trace? PiggyBac-ing toward pluripotency.

PMID- 19404252
TI  - Imaging intracellular RNA distribution and dynamics in living cells.
AB  - Powerful methods now allow the imaging of specific mRNAs in living cells. These
      methods enlist fluorescent proteins to illuminate mRNAs, use labeled
      oligonucleotide probes and exploit aptamers that render organic dyes fluorescent.
      The intracellular dynamics of mRNA synthesis, transport and localization can be
      analyzed at higher temporal resolution with these methods than has been possible
      with traditional fixed-cell or biochemical approaches. These methods have also
      been adopted to visualize and track single mRNA molecules in real time. This
      review explores the promises and limitations of these methods.

PMID- 19404253
TI  - Super-resolution video microscopy of live cells by structured illumination.
AB  - Structured-illumination microscopy can double the resolution of the widefield
      fluorescence microscope but has previously been too slow for dynamic live
      imaging. Here we demonstrate a high-speed structured-illumination microscope that
      is capable of 100-nm resolution at frame rates up to 11 Hz for several hundred
      time points. We demonstrate the microscope by video imaging of tubulin and
      kinesin dynamics in living Drosophila melanogaster S2 cells in the total internal
      reflection mode.

PMID- 19404254
TI  - Isolation of human iPS cells using EOS lentiviral vectors to select for
      pluripotency.
AB  - Induced pluripotent stem (iPS) cells may be of use in regenerative medicine.
      However, the low efficiency of reprogramming is a major impediment to the
      generation of patient-specific iPS cell lines. Here we report the first selection
      system for the isolation of human iPS cells. We developed the EOS (Early
      Transposon promoter and Oct-4 (Pou5f1) and Sox2 enhancers) lentiviral vector to
      specifically express in mouse and human embryonic stem cells but not in primary
      fibroblasts. The bicistronic EOS vector marked emerging mouse and human iPS cell
      colonies with EGFP, and we used puromycin selection to aid the isolation of iPS
      cell lines that expressed endogenous pluripotency markers. These lines
      differentiated into cell types from all three germ layers. Reporter expression
      was extinguished upon differentiation and therefore monitored the residual
      pluripotent cells that form teratomas. Finally, we used EOS selection to
      establish Rett syndrome-specific mouse and human iPS cell lines with known
      mutations in MECP2.

PMID- 19404256
TI  - Common genetic variants on 5p14.1 associate with autism spectrum disorders.
AB  - Autism spectrum disorders (ASDs) represent a group of childhood
      neurodevelopmental and neuropsychiatric disorders characterized by deficits in
      verbal communication, impairment of social interaction, and restricted and
      repetitive patterns of interests and behaviour. To identify common genetic risk
      factors underlying ASDs, here we present the results of genome-wide association
      studies on a cohort of 780 families (3,101 subjects) with affected children, and
      a second cohort of 1,204 affected subjects and 6,491 control subjects, all of
      whom were of European ancestry. Six single nucleotide polymorphisms between
      cadherin 10 (CDH10) and cadherin 9 (CDH9)-two genes encoding neuronal cell
      adhesion molecules-revealed strong association signals, with the most significant
      SNP being rs4307059 (P = 3.4 x 10(-8), odds ratio = 1.19). These signals were
      replicated in two independent cohorts, with combined P values ranging from 7.4 x
      10(-8) to 2.1 x 10(-10). Our results implicate neuronal cell-adhesion molecules
      in the pathogenesis of ASDs, and represent, to our knowledge, the first
      demonstration of genome-wide significant association of common variants with
      susceptibility to ASDs.

PMID- 19404258
TI  - High-frequency modification of plant genes using engineered zinc-finger
      nucleases.
AB  - An efficient method for making directed DNA sequence modifications to plant genes
      (gene targeting) is at present lacking, thereby frustrating efforts to dissect
      plant gene function and engineer crop plants that better meet the world's
      burgeoning need for food, fibre and fuel. Zinc-finger nucleases (ZFNs)-enzymes
      engineered to create DNA double-strand breaks at specific loci-are potent
      stimulators of gene targeting; for example, they can be used to precisely modify
      engineered reporter genes in plants. Here we demonstrate high-frequency ZFN
      stimulated gene targeting at endogenous plant genes, namely the tobacco
      acetolactate synthase genes (ALS SuRA and SuRB), for which specific mutations are
      known to confer resistance to imidazolinone and sulphonylurea herbicides.
      Herbicide-resistance mutations were introduced into SuR loci by ZFN-mediated gene
      targeting at frequencies exceeding 2% of transformed cells for mutations as far
      as 1.3 kilobases from the ZFN cleavage site. More than 40% of recombinant plants
      had modifications in multiple SuR alleles. The observed high frequency of gene
      targeting indicates that it is now possible to efficiently make targeted sequence
      changes in endogenous plant genes.

PMID- 19404257
TI  - Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.
AB  - Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with
      complex genetic origins. Previous studies focusing on candidate genes or genomic
      regions have identified several copy number variations (CNVs) that are associated
      with an increased risk of ASDs. Here we present the results from a whole-genome
      CNV study on a cohort of 859 ASD cases and 1,409 healthy children of European
      ancestry who were genotyped with approximately 550,000 single nucleotide
      polymorphism markers, in an attempt to comprehensively identify CNVs conferring
      susceptibility to ASDs. Positive findings were evaluated in an independent cohort
      of 1,336 ASD cases and 1,110 controls of European ancestry. Besides previously
      reported ASD candidate genes, such as NRXN1 (ref. 10) and CNTN4 (refs 11, 12),
      several new susceptibility genes encoding neuronal cell-adhesion molecules,
      including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to
      controls (P = 9.5 x 10(-3)). Furthermore, CNVs within or surrounding genes
      involved in the ubiquitin pathways, including UBE3A, PARK2, RFWD2 and FBXO40,
      were affected by CNVs not observed in controls (P = 3.3 x 10(-3)). We also
      identified duplications 55 kilobases upstream of complementary DNA AK123120 (P =
      3.6 x 10(-6)). Although these variants may be individually rare, they target
      genes involved in neuronal cell-adhesion or ubiquitin degradation, indicating
      that these two important gene networks expressed within the central nervous
      system may contribute to the genetic susceptibility of ASD.

PMID- 19404262
TI  - More food for thought.

PMID- 19404260
TI  - Mechanism of differential control of NMDA receptor activity by NR2 subunits.
AB  - N-methyl-d-aspartate (NMDA) receptors (NMDARs) are a major class of excitatory
      neurotransmitter receptors in the central nervous system. They form glutamate
      gated ion channels that are highly permeable to calcium and mediate activity
      dependent synaptic plasticity. NMDAR dysfunction is implicated in multiple brain
      disorders, including stroke, chronic pain and schizophrenia. NMDARs exist as
      multiple subtypes with distinct pharmacological and biophysical properties that
      are largely determined by the type of NR2 subunit (NR2A to NR2D) incorporated in
      the heteromeric NR1/NR2 complex. A fundamental difference between NMDAR subtypes
      is their channel maximal open probability (P(o)), which spans a 50-fold range
      from about 0.5 for NR2A-containing receptors to about 0.01 for receptors
      containing NR2C and NR2D; NR2B-containing receptors have an intermediate value
      (about 0.1). These differences in P(o) confer unique charge transfer capacities
      and signalling properties on each receptor subtype. The molecular basis for this
      profound difference in activity between NMDAR subtypes is unknown. Here we show
      that the subunit-specific gating of NMDARs is controlled by the region formed by
      the NR2 amino-terminal domain (NTD), an extracellular clamshell-like domain
      previously shown to bind allosteric inhibitors, and the short linker connecting
      the NTD to the agonist-binding domain (ABD). The subtype specificity of NMDAR
      P(o) largely reflects differences in the spontaneous (ligand-independent)
      equilibrium between open-cleft and closed-cleft conformations of the NR2-NTD.
      This NTD-driven gating control also affects pharmacological properties by setting
      the sensitivity to the endogenous inhibitors zinc and protons. Our results
      provide a proof of concept for a drug-based bidirectional control of NMDAR
      activity by using molecules acting either as NR2-NTD 'closers' or 'openers'
      promoting receptor inhibition or potentiation, respectively.

PMID- 19404261
TI  - Bmi1 regulates mitochondrial function and the DNA damage response pathway.
AB  - Mice deficient in the Polycomb repressor Bmi1 develop numerous abnormalities
      including a severe defect in stem cell self-renewal, alterations in thymocyte
      maturation and a shortened lifespan. Previous work has implicated de-repression
      of the Ink4a/Arf (also known as Cdkn2a) locus as mediating many of the aspects of
      the Bmi1(-/-) phenotype. Here we demonstrate that cells derived from Bmi1(-/-)
      mice also have impaired mitochondrial function, a marked increase in the
      intracellular levels of reactive oxygen species and subsequent engagement of the
      DNA damage response pathway. Furthermore, many of the deficiencies normally
      observed in Bmi1(-/-) mice improve after either pharmacological treatment with
      the antioxidant N-acetylcysteine or genetic disruption of the DNA damage response
      pathway by Chk2 (also known as Chek2) deletion. These results demonstrate that
      Bmi1 has an unexpected role in maintaining mitochondrial function and redox
      homeostasis and indicate that the Polycomb family of proteins can coordinately
      regulate cellular metabolism with stem and progenitor cell function.

PMID- 19404259
TI  - Precise genome modification in the crop species Zea mays using zinc-finger
      nucleases.
AB  - Agricultural biotechnology is limited by the inefficiencies of conventional
      random mutagenesis and transgenesis. Because targeted genome modification in
      plants has been intractable, plant trait engineering remains a laborious, time
      consuming and unpredictable undertaking. Here we report a broadly applicable,
      versatile solution to this problem: the use of designed zinc-finger nucleases
      (ZFNs) that induce a double-stranded break at their target locus. We describe the
      use of ZFNs to modify endogenous loci in plants of the crop species Zea mays. We
      show that simultaneous expression of ZFNs and delivery of a simple heterologous
      donor molecule leads to precise targeted addition of an herbicide-tolerance gene
      at the intended locus in a significant number of isolated events. ZFN-modified
      maize plants faithfully transmit these genetic changes to the next generation.
      Insertional disruption of one target locus, IPK1, results in both herbicide
      tolerance and the expected alteration of the inositol phosphate profile in
      developing seeds. ZFNs can be used in any plant species amenable to DNA delivery;
      our results therefore establish a new strategy for plant genetic manipulation in
      basic science and agricultural applications.

PMID- 19404263
TI  - Lubiprostone: trials and tribulations.

PMID- 19404265
TI  - Antioxidants for pain relief in chronic pancreatitis.

PMID- 19404264
TI  - Diagnosis of celiac disease in pediatric patients.

PMID- 19404266
TI  - Achievement of endoscopic hemostasis.

PMID- 19404268
TI  - How to choose the best preparation for colonoscopy.
AB  - The success and accuracy of colonoscopy is largely dependent on appropriate
      cleansing of the colon. The ideal bowel preparation should be safe, well
      tolerated and effective. Although colonoscopy preparations are vastly better than
      the earliest barium enemas used in X-ray regimens, none of the currently
      available formulations sufficiently fulfills the above criteria. Currently used
      techniques of colon cleansing include dietary and cathartic methods, gut lavage
      and the administration of phosphates. All of these methods are efficacious,
      particularly when administered in a split dose (one the evening before and one
      just before the planned colonoscopy). Gut lavage methods are the safest method;
      however, dietary and cathartic methods are also reasonably safe. Low-dose
      phosphate preparations are well tolerated, but safety concerns have led to the
      withdrawal of some phosphate products from the US market. A new oral sulfate
      product that achieves a desirable balance of safety, tolerability in patients and
      efficacy will shortly be introduced. Physicians should be aware of the range of
      colonoscopy preparations available and their limitations, so that the best
      preparation can be chosen for an individual patient.

PMID- 19404269
TI  - Secondary sclerosing cholangitis.
AB  - Secondary sclerosing cholangitis (SSC) is a chronic cholestatic biliary disease,
      characterized by inflammation, obliterative fibrosis of the bile ducts, stricture
      formation and progressive destruction of the biliary tree that leads to biliary
      cirrhosis. SSC is thought to develop as a consequence of known injuries or
      secondary to pathological processes of the biliary tree. The most frequently
      described causes of SSC are longstanding biliary obstruction, surgical trauma to
      the bile duct and ischemic injury to the biliary tree in liver allografts. SSC
      may also follow intra-arterial chemotherapy. Sclerosing cholangitis in critically
      ill patients is a largely unrecognized new form of SSC, and is associated with
      rapid progression to liver cirrhosis. The mechanisms leading to cholangiopathy in
      critically ill patients are widely unknown; however, the available clinical data
      indicate that ischemic injury to the intrahepatic biliary tree may be one of the
      earliest events in the development of this severe form of sclerosing cholangitis.
      Therapeutic options for most forms of SSC are limited, and patients with SSC who
      do not undergo transplantation have significantly reduced survival compared with
      patients with primary sclerosing cholangitis. Sclerosing cholangitis in
      critically ill patients, in particular, is associated with rapid disease
      progression and poor outcome.

PMID- 19404267
TI  - Eosinophilic esophagitis: the newest esophageal inflammatory disease.
AB  - Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory disease of
      undetermined pathophysiology that results in dense mucosal eosinophilia and
      esophageal dysfunction. In childhood, vague symptoms associated with GERD and
      feeding difficulties are the first manifestations of EoE. Adults typically
      present with dysphagia and food impaction. No pathognomonic features have been
      identified for EoE and, therefore, its diagnosis must be made on both clinical
      and histological grounds. Effective treatments rely on steroids and dietary
      exclusions.

PMID- 19404270
TI  - Carcinogenesis in IBD: potential targets for the prevention of colorectal cancer.
AB  - In patients with IBD, chronic colonic inflammation increases the risk of
      colorectal cancer, perhaps because inflammation predisposes these tissues to
      genomic instability. Carcinogenesis in the inflamed colon seems to follow a
      different sequence of genetic alterations than that observed in sporadic cancers
      in the uninflamed colon. In this Review, we focus on the genetic alterations in
      colitis-associated colorectal cancer that contribute to the acquisition of the
      essential hallmarks of cancer, and on how those alterations differ from sporadic
      colorectal cancers. Our intent is to provide a conceptual basis for categorizing
      carcinogenetic molecular abnormalities in IBD, and for understanding how cancer
      preventive therapies might target reversal of acquired abnormalities in specific
      biochemical pathways.

PMID- 19404272
TI  - The erosive potential of candy sprays.
AB  - OBJECTIVE: To determine the erosive potential of seven different commercially
      available candy sprays in vitro and in vivo. MATERIAL AND METHODS: The erosive
      potential was determined in vitro by measuring the pH and neutralisable acidity.
      The salivary pH and flow rate were measured in healthy volunteers after
      administration of a single dose of candy spray. RESULTS: Candy sprays have an
      extremely low pH (1.9-2.3) and a neutralisable acidity varying between 0.8-1.6 ml
      of 0.25M NaOH. In vivo, candy sprays induced a short-term 3.0 to 5.8-fold
      increase in salivary flow rate with a concomitant drop in salivary pH to values
      between 4.4 and 5.8. CONCLUSION: All candy sprays tested have an erosive
      potential. This information is of use for clinicians counselling juvenile
      patients with dental erosion.

PMID- 19404273
TI  - Serum androgen levels and their association to depression and Alzheimer dementia
      in a cohort of 75-year-old men over 5 years: results of the VITA study.
AB  - The role of androgens on cognitive function and mood is not well documented yet.
      We therefore evaluated all male participants (n=247, mean age 75.7 years) of a
      population-based study regarding testosterone, dehydroepiandrosterone sulfate
      (DHEAS), depression and Alzheimer Dementia (AD) for 5 years using the DSM-IV and
      NINCDS-ADRDA criteria. At study entry, low serum testosterone levels (<350 ng per
      100 ml) were present in 45 (30.8%), low DHEAS (<50 microg per 100 ml) in 44
      (30.1%), depression in 11 (7.5%) and AD in 7 (4.7%) men. After 5 years, the
      number of men with low testosterone levels increased to 52 (+15.5%), for low
      DHEAS to 57 (+29.5%) for depression to 34 (+219%) and for AD to 43 (+515%).
      Testosterone levels were not associated to prevalence or incidence of depression
      or dementia. Mean testosterone was 398.1 ng per 100 ml in depressive men and
      431.7 ng per 100 ml in those without depression (P=0.57) and 406.3 ng per 100 ml
      in those with AD versus 429.5 ng per 100 ml without AD (P=0.66).

PMID- 19404274
TI  - Clinicopathological characteristics and outcomes of patients with crescentic
      lupus nephritis.
AB  - There are few clinicopathologic and outcome data on patients with crescentic
      lupus nephritis, therefore, we determined factors of the disease by
      retrospectively reviewing the records of 327 patients diagnosed with lupus
      nephritis. Of these, 152 cases were regrouped as class IV-G, including 33
      patients with crescentic glomerulonephritis. Significantly, all patients with
      crescentic glomerulonephritis had acute kidney injury as compared with only about
      a quarter of the patients without the disease. On pathological evaluation,
      activity scores, chronicity indexes, relapse rates, and the frequency of positive
      serum anti-neutrophil cytoplasmic antibody (ANCA) were each significantly higher,
      whereas complete remission rates and renal outcomes, over a mean follow-up of 4
      years, were significantly poorer in patients with crescentic glomerulonephritis.
      Our study shows that crescentic glomerulonephritis was not rare in patients with
      lupus nephritis and that their long-term outcome was poor. The precise role of
      ANCA in the pathologic course of crescentic lupus nephritis remains to be
      determined.

PMID- 19404275
TI  - The link between obesity and albuminuria: adiponectin and podocyte dysfunction.
AB  - With the recent rise in the prevalence of obesity worldwide, obesity-related
      albuminuria is now being recognized as a critical risk factor for cardiovascular
      disease. However, there is an urgent need for a better understanding of this
      association. Recent clinical studies suggest that the adipocyte hormone
      adiponectin may play a key role in the development of obesity-related
      albuminuria. Moreover, studies with the adiponectin knockout mouse indicate that
      adiponectin can regulate podocyte function and thus contribute to the initial
      development of albuminuria. Future studies examining renal adipocyte cell biology
      are needed to develop preventive and therapeutic strategies for combatting the
      complications of obesity.

PMID- 19404271
TI  - Principles and clinical implications of the brain-gut-enteric microbiota axis.
AB  - While bidirectional brain-gut interactions are well known mechanisms for the
      regulation of gut function in both healthy and diseased states, a role of the
      enteric flora--including both commensal and pathogenic organisms--in these
      interactions has only been recognized in the past few years. The brain can
      influence commensal organisms (enteric microbiota) indirectly, via changes in
      gastrointestinal motility and secretion, and intestinal permeability, or
      directly, via signaling molecules released into the gut lumen from cells in the
      lamina propria (enterochromaffin cells, neurons, immune cells). Communication
      from enteric microbiota to the host can occur via multiple mechanisms, including
      epithelial-cell, receptor-mediated signaling and, when intestinal permeability is
      increased, through direct stimulation of host cells in the lamina propria.
      Enterochromaffin cells are important bidirectional transducers that regulate
      communication between the gut lumen and the nervous system. Vagal, afferent
      innervation of enterochromaffin cells provides a direct pathway for
      enterochromaffin-cell signaling to neuronal circuits, which may have an important
      role in pain and immune-response modulation, control of background emotions and
      other homeostatic functions. Disruption of the bidirectional interactions between
      the enteric microbiota and the nervous system may be involved in the
      pathophysiology of acute and chronic gastrointestinal disease states, including
      functional and inflammatory bowel disorders.

PMID- 19404276
TI  - Community-based interventions to optimize early childhood development in low
      resource settings.
AB  - OBJECTIVE: Interventions targeting the early childhood period (0 to 3 years) help
      to improve neuro-cognitive functioning throughout life. Some of the more low
      cost, low resource-intensive community practices for this age-group are play,
      reading, music and tactile stimulation. This research was conducted to summarize
      the evidence regarding the effectiveness of such strategies on child development,
      with particular focus on techniques that may be transferable to developing
      countries and to children at risk of developing secondary impairments. STUDY
      DESIGN: PubMed, PsycInfo, Embase, ERIC, CINAHL and Cochrane were searched for
      studies involving the above strategies for early intervention. Reference lists of
      these studies were scanned and other studies were incorporated based on snow
      balling. RESULT: Overall, 76 articles corresponding to 53 studies, 24 of which
      were randomized controlled trials, were identified. Sixteen of those studies were
      from low- and middle-income countries. Play and reading were the two commonest
      interventions and showed positive impact on intellectual development of the
      child. Music was evaluated primarily in intensive care settings. Kangaroo Mother
      Care, and to a lesser extent massage, also showed beneficial effects. Improvement
      in parent-child interaction was common to all the interventions. CONCLUSION: Play
      and reading were effective interventions for early childhood interventions in low
      and middle-income countries. More research is needed to judge the effectiveness
      of music. Kangaroo Mother Care is effective for low birth weight babies in
      resource poor settings, but further research is needed in community settings.
      Massage is useful, but needs more rigorous research prior to being advocated for
      community-level interventions.

PMID- 19404279
TI  - Estimated glomerular filtration rate: time for a performance review?
AB  - Measurement of the glomerular filtration rate (GFR) is an essential element in
      assessing renal function. Formulaic estimations of GFR (eGFRs) are widely used
      but have many pitfalls. Application of eGFR without adjustment for the effects of
      aging and gender results in overdiagnosis of chronic kidney disease (CKD). eGFR
      formulae also contain variables that independently influence the risk of CKD and
      cardiovascular disease. eGFR needs a performance review to foster its evolution
      as a clinically useful tool.

PMID- 19404280
TI  - The international realities of live donor kidney transplantation.
AB  - Horvat and coauthors report on trends in living kidney transplantation in 69
      countries, having assembled the data from registries, national societies, the
      medical literature, and direct contact with transplant centers. Assembling
      worldwide data on live-donor kidney transplants is a commendable accomplishment
      that serves the international transplant community well.

PMID- 19404281
TI  - Angiotensin II type 2 receptor in chronic kidney disease: the good side of
      angiotensin II?
AB  - Angiotensin II is believed to mediate blood pressure-independent progressive
      renal damage in chronic kidney disease (CKD). The evidence is less definitive
      than has been implied, and the studies by Benndorf et al. suggest that
      angiotensin II acting through its type 2 receptor may even have beneficial
      effects, although the responsible mechanisms remain to be defined. These and
      other data suggest that the concept of blood pressure-independent angiotensin
      signaling being uniformly deleterious in CKD is an oversimplification that needs
      re-evaluation.

PMID- 19404283
TI  - Treatment for hyperkalemia in hyporeninemic hypoaldosteronism.

PMID- 19404284
TI  - Factors aside from Helicobacter pylori play an important role in the occurrence
      of peptic ulcer in dialysis patients.

PMID- 19404286
TI  - About the association between high alkaline phosphatase and risk of death and
      hospitalization in dialysis patients.

PMID- 19404287
TI  - Is standard GLA gene mutation analysis definitive for the diagnosis of Fabry
      disease?

PMID- 19404289
TI  - The importance of expert education in enabling informed, activated patients.

PMID- 19404292
TI  - Vascular access calcification may be only an intermediate factor for mortality.

PMID- 19404293
TI  - Angiotensin-converting enzyme 2 (ACE2) gene and protein expression in diabetic
      patients without nephropathy.

PMID- 19404295
TI  - Response to 'Hormone therapy and loss of kidney function'.

PMID- 19404296
TI  - High-volume peritoneal dialysis in acute kidney injury.

PMID- 19404298
TI  - The Case. A child with metabolic acidosis and growth retardation.

PMID- 19404299
TI  - Chronic edema from protein-losing enteropathy: scintigraphic diagnosis.

PMID- 19404300
TI  - Peripheral blood gene expression profiling in Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is a common chronic autoimmune disease characterized by
      lymphocytic infiltration of exocrine glands. The affected cases commonly present
      with oral and ocular dryness, which is thought to be the result of inflammatory
      cell-mediated gland dysfunction. To identify important molecular pathways
      involved in SS, we used high-density microarrays to define global gene expression
      profiles in the peripheral blood. We first analyzed 21 SS cases and 23 controls,
      and identified a prominent pattern of overexpressed genes that are inducible by
      interferons (IFNs). These results were confirmed by evaluation of a second
      independent data set of 17 SS cases and 22 controls. Additional inflammatory and
      immune-related pathways with altered expression patterns in SS cases included B-
      and T-cell receptor, insulin-like growth factor-1, granulocyte macrophage-colony
      stimulating factor, peroxisome proliferator-activated receptor-alpha/retinoid X
      receptor-alpha and PI3/AKT signaling. Exploration of these data for relationships
      to clinical features of disease showed that expression levels for most interferon
      inducible genes were positively correlated with titers of anti-Ro/SSA (P<0.001)
      and anti-La/SSB (P<0.001) autoantibodies. Diagnostic and therapeutic approaches
      targeting interferon-signaling pathway may prove most effective in the subset of
      SS cases that produce anti-Ro/SSA and anti-La/SSB autoantibodies. Our results
      strongly support innate and adaptive immune processes in the pathogenesis of SS,
      and provide numerous candidate disease markers for further study.

PMID- 19404302
TI  - Diabetes drugs pass cardiovascular risk check.

PMID- 19404301
TI  - Variation in the upstream region of P-Selectin (SELP) is a risk factor for SLE.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Genome-wide
      linkage studies implicated a region containing the adhesion molecule P-Selectin.
      This family-based study revealed two regions of association within P-Selectin.
      The strongest signal, from a 21.4-kb risk haplotype, stretched from the promoter
      into the first two consensus repeat (CR) regions (P=8 x 10(-4)), with a second
      association from a 14.6-kb protective haplotype covering CR 2-9 (P=0.0198). The
      risk haplotype is tagged by the rare C allele of rs3753306, which disrupts the
      binding site of the trans-activating transcription factor HNF-1. One other
      variant (rs3917687) on the risk haplotype was significant after permutation
      (P(10000)<1 x 10(-5)), replicated in independent pseudo case-control analysis and
      was significant by meta-analysis (P=4.37 x 10(-6)). A third associated variant on
      the risk haplotype (rs3917657) replicated in 306 US SLE families and was
      significant in a joint UK-SLE data set after permutation. The protective
      haplotype is tagged by rs6133 (a non-synonymous variant in CR8 (P=9.00 x 10(-4)),
      which also shows association in the pseudo case-control analysis (P=1.09 x 10(
      3)) and may contribute to another signal in P-Selectin. We propose that
      polymorphism in the upstream region may reduce expression of P-Selectin, the
      mechanism by which this promotes autoimmunity is unknown, although it may reduce
      the production of regulatory T cells.

PMID- 19404303
TI  - Harnessing open innovation.

PMID- 19404305
TI  - Pharma industry strategic performance: 2008-2013E.

PMID- 19404306
TI  - Atherosclerosis drug fails to meet Phase III trial end point.

PMID- 19404307
TI  - NR2B antagonist pursued for treatment-resistant depression.

PMID- 19404309
TI  - Jingwu Zang. Interview by Bethan Hughes.

PMID- 19404310
TI  - Ustekinumab.

PMID- 19404311
TI  - Therapeutic targets to reduce cardiovascular disease in type 2 diabetes.
AB  - The potential cardiovascular risks that are associated with drugs for type 2
      diabetes have recently raised considerable clinical and regulatory concerns. As
      some risk factors for cardiovascular disease and type 2 diabetes are related,
      identifying agents that target shared underlying pathways and processes is an
      attractive therapeutic strategy. In this article, we review the background to and
      the implications of recent regulatory guidance on the development of new drugs
      for diabetes, and discuss the potential cardiovascular effects of selected
      classes of diabetes drugs that are currently being investigated.

PMID- 19404314
TI  - Adding nebivolol to ongoing antihypertensive therapy improves blood pressure and
      response rates in patients with uncontrolled stage I-II hypertension.
AB  - This study assessed blood pressure (BP) reductions and response rates following
      addition of nebivolol to ongoing antihypertensive therapy in patients with
      uncontrolled stage I-II hypertension despite antihypertensive treatment. Patients
      with an average sitting diastolic BP (SiDBP) > or =90 and < or =109 mm Hg while
      taking an antihypertensive regimen were included in this double-blind, placebo
      controlled, parallel-group study. The primary efficacy end point was reduction
      from baseline to week 12 in mean trough SiDBP. In total, 669 patients were
      randomized to once-daily nebivolol 5, 10 or 20 mg or placebo. Addition of
      nebivolol 5, 10 and 20 mg significantly reduced BP; placebo-subtracted least
      squares mean reductions in trough SiDBP were -3.3, -3.5 and -4.6 mm Hg,
      respectively (P<0.001) and -5.7, -3.7 and -6.2 mm Hg in trough sitting systolic
      BP (SiSBP), respectively (P< or =0.015). Adding nebivolol 5-20 mg resulted in
      significantly more responders (SiDBP <90 or > or =10 mm Hg reduction; range: 53.0
      65.1 vs 41.3% with placebo; P< or =0.028) and significantly better control rates
      (SiSBP/SiDBP <140/90 mm Hg; range: 41.3-52.7 vs 29.3% with placebo; P< or
      =0.029). Nebivolol was well tolerated; the incidence of adverse events with
      nebivolol was similar to that with placebo (40.2 vs 38.9%, respectively;
      P=0.763). Addition of once-daily nebivolol to ongoing antihypertensive therapy
      provided significant additional BP reductions and better response rates in
      patients with uncontrolled hypertension and was well tolerated.

PMID- 19404312
TI  - Targeting the CNS to treat type 2 diabetes.
AB  - Research on the role of peripheral organs in the regulation of glucose
      homeostasis has led to the development of various monotherapies that aim to
      improve glucose uptake and insulin action in these organs for the treatment of
      type 2 diabetes. It is now clear that the central nervous system (CNS) also plays
      an important part in orchestrating appropriate glucose metabolism, with
      accumulating evidence linking dysregulated CNS circuits to the failure of normal
      glucoregulatory mechanisms. There is evidence that there is substantial overlap
      between the CNS circuits that regulate energy balance and those that regulate
      glucose levels, suggesting that their dysregulation could link obesity and
      diabetes. These findings present new targets for therapies that may be capable of
      both inducing weight loss and improving glucose regulation.

PMID- 19404313
TI  - Therapies for hyperglycaemia-induced diabetic complications: from animal models
      to clinical trials.
AB  - Long-term diabetes increases the likelihood of developing secondary damage to
      numerous systems, and these complications represent a substantial cause of
      morbidity and mortality. Establishing the causes of diabetes remains the key step
      towards eradicating the disease, but the prevention and amelioration of diabetic
      complications is equally important for the millions of individuals who already
      have the disease or are likely to develop it before prophylaxis or a cure become
      routinely available. In this Review, we focus on four common complications of
      diabetes, discuss the range of pathologies that are precipitated by
      hyperglycaemia and highlight emerging targets for therapeutic intervention.

PMID- 19404315
TI  - Low-Sodium DASH reduces oxidative stress and improves vascular function in salt
      sensitive humans.
AB  - Salt induces oxidative stress in salt-sensitive (SS) animals and man. It is not
      known whether in SS subjects the low-sodium dietary approaches to stop
      hypertension (LS-DASH) reduces oxidative stress more than DASH, which is high in
      antioxidants. To assess the effects of DASH and LS-DASH on oxidative stress, 19
      volunteers were studied after 3 weeks of a standardized usual low fruits and
      vegetables diet (ULFV), followed by 3 weeks on DASH (both diets approximately 120
      mmol Na(+) per day), then 3 weeks on LS-DASH (60 mmol Na(+) per day). SS was
      defined as systolic blood pressure >or=5 mm Hg lower on LS-DASH than DASH. In SS
      subjects (N=9), systolic blood pressure was lower on LS-DASH (111.0+/-2.0 mm Hg)
      than DASH (118.0+/-2.2, P<0.01) and ULFV (122.3+/-2.7, P=0.002). In salt
      resistant (SR) volunteers (N=10), systolic blood pressure was lower on DASH
      (113.0+/-1.6) than ULFV (119.0+/-1.8, P<0.05) but not LS-DASH (115.7+/-1.8).
      Urine F2-isoprostanes, a marker of oxidative stress, were lower in SS subjects on
      LS-DASH (1.69+/-0.24) than ULFV (3.09+/-0.50, P<0.05) and marginally lower than
      DASH (2.46+/-0.44, P<0.20). F2-isoprostanes were not different among the three
      diets in SR volunteers (2.18+/-0.29, 2.06+/-0.29, 2.27+/-0.53, respectively).
      Aortic augmentation index, a measure of vascular stiffness, was lower in SS
      subjects on LS-DASH than either DASH or ULFV, and lower on DASH than ULFV in SR
      volunteers. In SS but not SR subjects, LS-DASH is associated with lower values
      for F2-isoprostanes and the aortic augmentation index. The results suggest that
      LS-DASH decreases oxidative stress, improves vascular function and lowers blood
      pressure in SS but not SR volunteers.

PMID- 19404317
TI  - MEK inhibitors potentiate dexamethasone lethality in acute lymphoblastic leukemia
      cells through the pro-apoptotic molecule BIM.
AB  - Glucocorticoids (GCs) are common components of many chemotherapeutic regimens for
      lymphoid malignancies. GC-induced apoptosis involves an intrinsic mitochondria
      dependent pathway. We and others have shown that BIM (BCL-2 interacting mediator
      of cell death), a BH3-only pro-apoptotic protein, is up-regulated by
      dexamethasone (Dex) treatment in acute lymphoblastic leukemia (ALL) cells and
      plays an essential role in Dex-induced apoptosis. Furthermore, BIM is inactivated
      by extracellular signal-regulated kinase (ERK)-mediated phosphorylation. We
      therefore hypothesized co-treatment with Dex and MEK/ERK inhibitors would promote
      apoptosis in ALL cells through BIM up-regulation and activation. We show here
      that MEK inhibitors (PD184352 and PD98059) synergistically enhance Dex lethality
      in a variety of ALL cells and in two primary ALL specimens. Co-treatment with Dex
      and PD184352 results in BIM accumulation, pro-apoptotic BAX/BAK activation, and
      cytochrome c release from mitochondria. Down-regulation of BIM by short-hairpin
      RNA (shRNA) in ALL cells suppressed BAX/BAK activation, cytochrome c release, and
      cell death by Dex/PD184352 co-treatment. BIM accumulated by this treatment
      sequesters anti-apoptotic BCL-XLMCL-1, resulting in the release of BAK from these
      anti-apoptotic molecules. This study provides a rational foundation for future
      attempts to improve the activity of GCs with clinically relevant pharmacologic
      MEK inhibitors in the treatment of ALL and possibly other hematologic
      malignancies.

PMID- 19404318
TI  - Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib
      therapy for chronic myeloid leukemia.
AB  - Imatinib is the current standard of care in the treatment of chronic myeloid
      leukemia (CML), inducing durable responses and prolonged progression-free
      survival. However, plasma exposure to the drug from a given dosing regimen can
      vary widely among patients. Reasons for this may include incomplete adherence,
      intrinsic variations in the metabolism of imatinib, and drug-drug interactions.
      Data from two recent studies have shown a correlation between imatinib trough
      plasma concentration and clinical response, leading to suggestions that
      maintaining imatinib blood concentrations above approximately 1000 ng/ml might be
      associated with improved outcomes. In patients who do not respond as well as
      expected to initial imatinib treatment, measurement of trough plasma
      concentration could assist with decisions about whether to increase the dose.
      Blood-level testing may also be helpful in other clinical scenarios: for example,
      when poor adherence is suspected, adverse reactions are unusually severe, or
      there is a possible drug-drug interaction. Further work is required to confirm
      prospectively the link between imatinib plasma concentrations and response, and
      to define effective trough concentrations in different patient populations.
      However, based on the current data, imatinib blood-level testing seems to be a
      useful aid when making clinical decisions in CML.

PMID- 19404319
TI  - Absence of somatic mutations of NEMO in keratoacanthoma.

PMID- 19404320
TI  - Asymmetry in siRNA design.

PMID- 19404321
TI  - Gene therapy for cardiomyocytes, a heart beat away.

PMID- 19404322
TI  - Recombinant DNA advisory committee updates recommendations on gene transfer for x
      linked severe combined immunodeficiency.

PMID- 19404325
TI  - Dotting the I's and crossing the T's: integration analyses in transduced patient
      T cells.

PMID- 19404326
TI  - Abundance, composition, diversity and novelty of soil Proteobacteria.
AB  - Small subunit (16S) rRNA gene surveys generating near full-length 16S rRNA clones
      offer a unique opportunity for in-depth phylogenetic analysis to highlight the
      breadth of diversity within various major bacterial phyla encountered in soil.
      This study offers a detailed phylogenetic analysis of the Proteobacteria
      affiliated clones identified from 13,001 nearly full-length 16S rRNA gene clones
      derived from Oklahoma tall-grass prairie soil. Proteobacteria was the most
      abundant phylum in the community, and comprised 25% of the total clones. The most
      abundant and diverse class within the Proteobacteria was Alphaproteobacteria,
      followed by the Delta-, Beta- and Gammaproteobacteria. Members of the Epsilon-
      and Zetaproteobacteria were not detected in the dataset. Our analysis identified
      15 novel order-level and 48 novel family-level Proteobacteria lineages. In
      addition, we show that the majority of Proteobacteria clones in the dataset
      belong to orders and families containing no described cultivated representatives
      (50% and 65%, respectively). An examination of the ecological distribution of the
      six most abundant Proteobacteria lineages in this dataset with no characterized
      pure culture representatives provided important information regarding their
      global distribution and environmental preferences. This level of novel
      phylogenetic diversity indicates that our understanding of the functions of soil
      microorganisms, even those belonging to phyla with numerous and diverse well
      characterized cultured representatives such as the Proteobacteria, remains far
      from adequate.

PMID- 19404327
TI  - The genome sequence of the psychrophilic archaeon, Methanococcoides burtonii: the
      role of genome evolution in cold adaptation.
AB  - Psychrophilic archaea are abundant and perform critical roles throughout the
      Earth's expansive cold biosphere. Here we report the first complete genome
      sequence for a psychrophilic methanogenic archaeon, Methanococcoides burtonii.
      The genome sequence was manually annotated including the use of a five-tiered
      evidence rating (ER) system that ranked annotations from ER1 (gene product
      experimentally characterized from the parent organism) to ER5 (hypothetical gene
      product) to provide a rapid means of assessing the certainty of gene function
      predictions. The genome is characterized by a higher level of aberrant sequence
      composition (51%) than any other archaeon. In comparison to hyper/thermophilic
      archaea, which are subject to selection of synonymous codon usage, M. burtonii
      has evolved cold adaptation through a genomic capacity to accommodate highly
      skewed amino-acid content, while retaining codon usage in common with its
      mesophilic Methanosarcina cousins. Polysaccharide biosynthesis genes comprise at
      least 3.3% of protein coding genes in the genome, and Cell wall, membrane,
      envelope biogenesis COG genes are overrepresented. Likewise, signal transduction
      (COG category T) genes are overrepresented and M. burtonii has a high 'IQ' (a
      measure of adaptive potential) compared to many methanogens. Numerous genes in
      these two overrepresented COG categories appear to have been acquired from
      epsilon- and delta-Proteobacteria, as do specific genes involved in central
      metabolism such as a novel B form of aconitase. Transposases also distinguish M.
      burtonii from other archaea, and their genomic characteristics indicate they have
      an important role in evolving the M. burtonii genome. Our study reveals a
      capacity for this model psychrophile to evolve through genome plasticity
      (including nucleotide skew, horizontal gene transfer and transposase activity)
      that enables adaptation to the cold, and to the biological and physical changes
      that have occurred over the last several thousand years as it adapted from a
      marine to an Antarctic lake environment.

PMID- 19404328
TI  - Focus on host subversion.
AB  - A collection of seven reviews surveys how microorganisms subvert host cell
      biology.

PMID- 19404329
TI  - Genetic privacy and piracy.
AB  - On the eve of a decision on a new gene diagnostics law in Germany, the debate
      about risks and benefits, although important, must not derail essential
      legislation.

PMID- 19404330
TI  - Virus entry by macropinocytosis.
AB  - As obligatory intracellular parasites, viruses rely on host-cell functions for
      most aspects of their replication cycle. This is born out during entry, when most
      viruses that infect vertebrate and insect cells exploit the endocytic activities
      of the host cell to move into the cytoplasm. Viruses belonging to vaccinia,
      adeno, picorna and other virus families have been reported to take advantage of
      macropinocytosis, an endocytic mechanism normally involved in fluid uptake. The
      virus particles first activate signalling pathways that trigger actin-mediated
      membrane ruffling and blebbing. Usually, this is followed by the formation of
      large vacuoles (macropinosomes) at the plasma membrane, internalization of virus
      particles and penetration by the viruses or their capsids into the cytosol
      through the limiting membrane of the macropinosomes. We review the molecular
      machinery involved in macropinocytosis and describe what is known about its role
      in virus entry.

PMID- 19404331
TI  - Targeting of immune signalling networks by bacterial pathogens.
AB  - Host defence against microbial pathogens requires appropriate coordination of
      multiple signalling pathways. These pathways are triggered by innate immune
      recognition of conserved microbial molecules, and initiate an inflammatory
      cascade that involves recruitment of leukocytes to the site of infection,
      activation of antimicrobial effector mechanisms and induction of an adaptive
      immune response that promotes clearance of infection and long-term immune memory.
      Microbial pathogens possess specialized proteins termed virulence factors, which
      interfere with host defence at several levels. Many virulence factors from
      diverse pathogens have been identified in recent years and their functions linked
      to disruption of essential processes of immune defence, from signalling to
      phagocytosis. Although the diversity of pathogens and virulence factors is
      immense, common themes have emerged with regard to how microbial pathogens
      interfere with immune responses. Here we discuss recent advances in our
      understanding of how virulence factors target innate and adaptive immune
      responses, focusing on bacterial pathogens. We also propose that pathogens
      responsible for causing acute infection tend to target central components (hubs)
      of cellular signalling pathways, causing global disruption of the host response.
      By contrast, pathogens that cause chronic or persistent infections tend to target
      more peripheral signalling network components (nodes) to promote pathogen
      persistence.

PMID- 19404333
TI  - From cell differentiation to the cell cycle: how failing in biochemistry led to
      success in morphology.

PMID- 19404334
TI  - Breaking a temporal barrier: signalling crosstalk regulates the initiation of
      border cell migration.
AB  - Correct timing of developmental events is crucial for generating a normal
      organism. During oogenesis in Drosophila melanogaster, migration of border cells
      occurs in a defined temporal window and requires Jak/Stat and steroid hormone
      signalling. The initiation of border-cell migration is now shown to be timed by
      Jak/Stat-mediated downregulation of the BTB domain transcriptional regulator
      Abrupt, which acts as a negative regulator of steroid hormone signalling.

PMID- 19404332
TI  - Viral avoidance and exploitation of the ubiquitin system.
AB  - The versatility of ubiquitin in regulating protein function and cell behaviour
      through post-translational protein modification makes it a particularly
      attractive target for viruses. Here we review how viruses manipulate the
      ubiquitin system to favour their propagation by redirecting cellular ubiquitin
      enzymes or encoding their own ubiquitin components to enable replication, egress
      and immune evasion. These studies not only reveal the many cellular processes
      requiring ubiquitin but also illustrate how viruses usurp their host cells.

PMID- 19404335
TI  - Smurf1 zaps the talin head.
AB  - Focal adhesion turnover is essential for cell migration. New results show that
      the talin head liberated from talin by calpain II cleavage has a key role in
      these events, and that its levels are tightly regulated by Smurf1-mediated
      ubiquitylation counteracted by Cdk5-mediated phosphorylation.

PMID- 19404338
TI  - Expression of thyroglobulin on follicular dendritic cells of thyroid mucosa
      associated lymphoid tissue (MALT) lymphoma.
AB  - Reportedly, thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is closely
      associated with Hashimoto's thyroiditis. However, it remains unknown which
      antigen is closely associated with thyroid MALT lymphoma. We examined whether B
      cell response to thyroglobulin (Tg), which is a common thyroid-specific
      autoantigen, is related etiologically to the pathogenesis of thyroid MALT
      lymphoma. Expression of human Tg antigens and Cluster of differentiation (CD) 35
      was examined immunohistochemically in 15 cases of thyroid MALT lymphoma using
      paraffin-embedded, formalin-fixed tissue specimens. In all cases of thyroid MALT
      lymphoma, human Tg was detected immunohistochemically in the follicular
      epithelial cells and follicular dendritic cells (FDCs). These FDCs were positive
      by double immunostaining for anti-human Tg rabbit polyclonal antibody (Ab) and
      for CD35. Results showed that the Tg, a thyroid autoantigen, had immunostained
      the germinal center of the thyroid MALT lymphoma. The Tg was present in the FDCs,
      as revealed by the staining pattern of the germinal center;this fact was
      confirmed by double immunostaining of anti-human Tg mouse monoclonal Ab and anti
      CD35 mouse monoclonal Ab. The results of our study suggest that Tg is an
      autoantigen that is recognized by thyroid MALT lymphoma cells.

PMID- 19404336
TI  - SCAI blocks MAL-evolent effects on cancer cell invasion.
AB  - SCAI is a newly discovered protein that reduces cancer cell invasiveness. SCAI
      inhibits the MAL/SRF transcriptional activator complex that is downstream of Rho
      GTPase and actin, resulting in reduced expression of beta1-integrins and loss of
      invasive potential.

PMID- 19404339
TI  - The 3'-untranslated region of ADAMTS1 regulates its mRNA stability.
AB  - ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an
      inflammatory-induced gene. We have previously reported that ADAMTS1 was strongly
      but transiently expressed in the infarcted heart. In this study, we investigated
      whether a 3'-untranslated region (UTR) affects the mRNA stability of this gene.
      When stimulated with tissue necrosis factor (TNF)-alpha, the expression level of
      ADAMTS1 mRNA rapidly increased, but the induction of ADAMTS1 mRNA peaked at 6h
      after stimulation, after which the expression levels of ADAMTS1 mRNA decreased.
      The 3'-UTR ADAMTS1 mRNA contains multiple adenine and uridine-rich elements,
      suggesting that the 3'-UTR may regulate gene stability. The addition of
      actinomycin D, an RNA synthesis inhibitor, demonstrated the decay of induced
      ADAMTS1 mRNA by TNF-alpha. Furthermore, a region containing multiple AUUUA motifs
      within the ADAMTS1 3'-UTR destabilized transfected Enhanced Green Fluorescence
      Protein (EGFP) mRNA expression. These results demonstrated that the ADAMTS1 3'
      UTR may regulate the expression of ADAMTS1 mRNA.

PMID- 19404340
TI  - Doppler echocardiographic assessment of left ventricular diastolic function in
      chronic hypoxic rats.
AB  - Little information is available on the mechanism of diastolic left ventricular
      (LV) dysfunction in patients with chronic respiratory disease complicated by
      hypoxia. The purpose of this study was to investigate how chronic hypoxia impairs
      LV diastolic function in an hypoxic animal model. Thirty-six male Wistar rats 8
      weeks old were assigned to normoxia (N), chronic hypoxia (CH), and re-normoxia
      (RN) groups, 12 rats per group. The N group rats were kept in ambient air for 8
      weeks, while the CH group was kept hypoxic for 8 weeks. After 8 weeks of hypoxia
      the RN group rats were kept for a further 8 weeks in ambient air. LV systolic and
      diastolic functions, as well as right ventricular (RV) function, were analyzed
      using Doppler echocardiography;we also measured the hematocrit, and weighed the
      LV and RV. Hematocrit, RV weight/body weight, and RV weight/LV weight were higher
      in the CH group than in the other 2 groups. However, most of these parameters
      returned to normoxia levels after re-normoxia. In the CH group, LV dimension and
      area were smaller than in the other 2 groups. LV systolic function was preserved
      in all groups;however, in the CH group, mitral flow showed a restrictive pattern,
      while pulmonary flow demonstrated a pulmonary hypertensive pattern with prolonged
      RV ejection time. In conclusion, chronic hypoxia induced pulmonary hypertension
      and RV hypertrophy. Although LV systolic function was preserved, diastolic
      function was impaired in hypoxia. Ventricular interaction may impair LV diastolic
      function.

PMID- 19404341
TI  - Relationship of psychological factors with physical activity stage of change in
      prime-and middle-aged Japanese.
AB  - The present study aimed to investigate the status of physical activity and the
      differences in psychological factors associated with physical activity from the
      perspective of transtheoretical model stages between prime- and middle-aged
      Japanese. The study involved 375 prime-aged volunteers (175 men, 200 women) and
      557 middle-aged volunteers (247 men, 310 women) living in Kuse, a town in Okayama
      Prefecture, Japan. We found that the prime-aged men at the preparation stage had
      significantly higher self-efficacy scores than at the contemplation stage
      (p<0.01). Middle-aged men had significantly higher self-efficacy scores at the
      contemplation stage than at the precontemplation stage (p<0.001). Middle-aged
      women, meanwhile, had significantly higher self-efficacy scores at the
      maintenance stage than at the action stage (p<0.01), and at the contemplation
      stage than at the precontemplation stage (p<0.001). The present findings provide
      valuable information about the differences in psychological factors affecting
      physical activity between prime-aged and middle-aged community-dwelling Japanese.
      This information may be useful to health professionals as they develop effective
      community-based intervention programs for target populations.

PMID- 19404342
TI  - Beneficial effects of Vitis coignetiae Pulliat leaves on nonalcoholic
      steatohepatitis in a rat model.
AB  - Vitis coignetiae Pulliat (Yamabudo) is used as a health juice and wine based on
      the abundant polyphenols and anthocyanins in its fruit. However, it is not known
      whether the leaves of this plant confer similar benefits. This study investigated
      the hepatoprotective effects of aqueous extracts from Vitis coignetiae Pulliat
      leaves (VCPL) in an animal model of nonalcoholic steatohepatitis (NASH). Rats
      were fed a choline-deficient high-fat diet for four weeks to generate fatty
      livers. NASH was induced by oxidative stress loading. Ten weeks later, blood and
      liver samples were collected from anesthetized animals and assessed
      biochemically, histologically, and histochemically to determine the extent of
      oxidative stress injury and the overall effects of VCPL. Six-week VCPL extract
      supplementation reduced serum levels of liver enzymes, decreased CYP2E1
      induction, increased plasma antioxidant activities and delayed the progression of
      liver fibrosis. The findings suggested that VCPL has strong radical-scavenging
      activity and may be beneficial in preventing NASH progression.

PMID- 19404343
TI  - Supportive intervention using a mobile phone in behavior modification.
AB  - The authors previously developed a mobile ecological momentary assessment (EMA)
      system as a real-time data collection device using a mobile phone. In this study,
      a real-time advice function and real-time reporting function were added to the
      previous system as a supportive intervention. The improved system was found to
      work effectively and was applied to several clinical cases, including patients
      with depressive disorder, dizziness, smoking habit, and bronchial asthma. The
      average patient compliance rate was high (89%) without the real-time advice and
      higher (93%) with the advice. The trends in clinical data for patients using a
      mobile EMA with/without the new function were analyzed for up to several months.
      In the case of dizziness, an improving trend in its clinical data was observed
      after applying the real-time advice, and in the case of depressive disorder, a
      stabilizing trend was observed. The mobile EMA system with the real-time advice
      function could be useful as a supportive intervention in behavior modification
      and for motivating patients in self-management of their disease.

PMID- 19404345
TI  - An optical coherence microscope for 3-dimensional imaging in developmental
      biology.
AB  - An optical coherence microscope (OCM) has been designed and constructed to
      acquire 3-dimensional images of highly scattering biological tissue. Volume
      rendering software is used to enhance 3-D visualization of the data sets. Lateral
      resolution of the OCM is 5 mm (FWHM), and the depth resolution is 10 mm (FWHM) in
      tissue. The design trade-offs for a 3-D OCM are discussed, and the fundamental
      photon noise limitation is measured and compared with theory. A rotating 3-D
      image of a frog embryo is presented to illustrate the capabilities of the
      instrument.

PMID- 19404346
TI  - A pulsed finite-difference time-domain (FDTD) method for calculating light
      scattering from biological cells over broad wavelength ranges.
AB  - We combine the finite-difference time-domain method with pulse response
      techniques in order to calculate the light scattering properties of biological
      cells over a range of wavelengths simultaneously. The method we describe can be
      used to compute the scattering patterns of cells containing multiple
      heterogeneous organelles, providing greater geometric flexibility than Mie theory
      solutions. Using a desktop computer, we calculate the scattering patterns for
      common homogeneous models of biological cells and also for more complex
      representations of cellular morphology. We find that the geometry chosen
      significantly impacts scattering properties, emphasizing the need for careful
      consideration of appropriate theoretical models of cellular scattering and for
      accurate microscopic determination of optical properties.

PMID- 19404347
TI  - Measurement of polarization mode dispersion vectors using the polarization
      dependent signal delay method.
AB  - We describe a new time-domain method for determining the vector components of
      polarization-mode dispersion from measurements of the mean signal delays for four
      polarization launches. Using sinusoidal amplitude modulation and sensitive phase
      detection, we demonstrate that the PMD vector components measured with the new
      method agree with results obtained from the more traditional Muller Matrix
      Method.

PMID- 19404348
TI  - Resolved object imaging and localization with the use of a backpropagation
      algorithm.
AB  - Optical diffusion tomography is an emerging technology that generates images of
      objects imbedded in turbid media using scattered light. To date, however, most
      demonstrations of this technology use a sphere or a collection of spheres as the
      imbedded object. Here we use a backpropagation algorithm and a planar geometry to
      reconstruct images of resolved objects (airplane models) imbedded in tissue
      phantoms. In addition, we show that we can locate the resolved objects in three
      dimensions in the turbid medium using only a single planar view. The imaging
      system uses diffuse photon density waves produced using kilohertz modulation
      (that is, essentially dc illumination).

PMID- 19404349
TI  - A low cost adaptive optics system using a membrane mirror.
AB  - A low cost adaptive optics system constructed almost entirely of commercially
      available components is presented. The system uses a 37 actuator membrane mirror
      and operates at frame rates up to 800Hz using a single processor. Numerical
      modelling of the membrane mirror is used to optimize parameters of the system.
      The dynamic performance of the system is investigated in detail using a
      diffractive wavefront generator based on a ferroelectric spatial light modulator.
      This is used to produce wavefronts with time-varying aberrations. The ability of
      the system to correct for Kolmogorov turbulence with different strengths and
      effective wind speeds is measured experimentally using the wavefront generator.

PMID- 19404350
TI  - Real-time visualization of domain formation in periodically poled lithium
      niobate.
AB  - We present video footage demonstrating real-time visualization of domain
      formation in periodically-poled lithium niobate (PPLN). This in-situ, non
      destructive technique provides important visual information concerning the global
      quality and dynamics of domain patterning during the fabrication of PPLN.

PMID- 19404351
TI  - Manufacturing of a fiber optic Young's double pinhole interferometer for use as a
      3-D profilometer.
AB  - The method used to manufacture a Young's double pinhole interferometer is dis
      ussed. This interferometer is destined to be used in a surface profilometer using
      two wavelengths so that the zero order fringe can be determined. Hence stringent
      requirements are placed on the absolute length difference between the two output
      fibers of a single mode coupler. These requirements are discussed along with the
      manufacturing process. The interferometer is shown along with measurements
      showing a length difference on the order of 6microm.

PMID- 19404352
TI  - Transparency effects on powder speckle decorrelation.
AB  - Laser speckle decorrelation has previously been applied to measure the mean
      powder size of bulk powder beds and the roughness of porous rocks. The angular
      decorrelation rate of laser speckle from bulk powder beds correlates strongly
      with the mean powder size. However it was found that the angular decorrelation
      rates of transparent powders were much higher than those of opaque or dyed
      powders of the same size distribution. The accuracy of size measurements could be
      severely compromised if transparency effects were not compensated. Monte Carlo
      modelling of remitted photon path lengths in a powder bed suggests and
      experimental data supports that diffuse reflectance data may be used to correct
      for transparency effects on angular decorrelation rate data.

PMID- 19404353
TI  - Spectral response of plasmon resonant nanoparticles with a non-regular shape.
AB  - We study the plasmon resonances of 10 (nm)--100 (nm) two-dimensional metal
      particles with a non-regular shape. Movies illustrate the spectral response of
      such particles in the optical range. Contrary to particles with a simple shape
      (cylinder, ellipse) non-regular particles exhibit many distinct resonances over a
      large spectral range. At resonance frequencies, extremely large enhancements of
      the electromagnetic fields occur near the surface of the particle, with
      amplitudes several hundred-fold that of the incident field. Implications of these
      strong and localized fields for nano-optics and surface enhanced Raman scattering
      (SERS) are also discussed.

PMID- 19404354
TI  - Self-starting mode-locked cavity-dumped femtosecond Ti:sapphire laser employing a
      semiconductor saturable absorber mirror.
AB  - We report on a novel design of a cavity-dumped Ti:sapphire laser employing a
      semiconductor saturable absorber mirror (SESAM) to assure self-starting. With
      pump powers as low as 3.5 W, a stable operation is achieved, producing pulses of
      about 90 fs duration and single pulse energies of up to 34 nJ at 800 kHz dumping
      rate. The suppression ratios of the preceeding and consecutive pulses are better
      than 350:1, thus making this system an ideal excitation source for time
      correlated photon counting experiments.

PMID- 19404355
TI  - A thin film of short oriented linear Frenkel chains as an optical bistable
      element.
AB  - A numerical study of reflectivity and transmittivity of an ensemble of short
      oriented linear Frenkel chains, which forms a thin film with a thickness of the
      order of an optical wavelength, is carried out. The eigenstates of a single chain
      are considered to be of a collective (excitonic) origin. A distribution of chains
      over lengths resulting in inhomogeneous broadening of the exciton optical
      transition is taken into account. We report a bistable behavior of both
      reflectivity and transmittivity of the film in a spectral domain close to the
      exciton resonance, caused by saturation of the nonlinear refraction index.
      Estimates of driving parameters show that thin films of oriented J-aggregates of
      polymethine dyes deposited on a dielectric substrate seem to be a suitable object
      for observation of the predicted behavior.

PMID- 19404356
TI  - Resonance in scattering and absorption from large noble gas clusters.
AB  - Light scattering in large noble gas clusters irradiated by intense laser pulses
      was studied and compared to absorption measurements. The scattering signal shows
      the presence of a peak, when the pulse width was varied, similar to one
      previously reported in absorption measurements. The peak of the scattering,
      however, occurs at a longer pulse width than for absorption. This result
      disagrees with a simple simulation and may be due to propagation or non-linear
      effects not included in the model.

PMID- 19404357
TI  - Scanning laser reflectometry of retinal and subretinal tissues.
AB  - Measurements of the human ocular fundus that make use of the light returning
      through the pupil are called reflectometry. Early reflectometry studies were
      limited by poor light return from the retina and strong reflections from the
      anterior surface of the eye. Artifacts produced misleading results in diseases
      like age-related macular degeneration. Novel laser sources, scanning, confocal
      optics, and digital imaging provide improved sampling of the signal from the
      tissues of interest: photoreceptors and retinal pigment epithelial cells. A wider
      range of wavelengths is now compared, including the near infrared. Reflectometry
      now provides functional mapping, even in severe pathology.

PMID- 19404358
TI  - Diffusion of Cs atoms in Ne buffer gas measured by optical magnetic resonance
      tomography.
AB  - Optical magnetic resonance tomography uses optical pumping and the paramagnetic
      Faraday effect to image spin density distributions in optically thin media. In
      this paper we present an apparatus that allows to measure the distribution of
      spin-polarized Cs atoms, which we applied to study the diffusion of Cs in Ne
      buffer gas by time-resolved 2D-mapping of the evolution of an initial
      inhomogeneous spin distribution. The diffusion constant D0 for Cs in a Ne buffer
      gas of 1013 mbar is determined as 0.20(1) cm2?s.

PMID- 19404359
TI  - Delivery of F2-excimer laser light by aluminum hollow fibers.
AB  - A hollow fiber composed of a glass-tube substrate and an aluminum thin film
      coated upon the inside of the tube delivers F2-excimer laser light. A smooth,
      aluminum thin film was deposited by using metal-organic chemical vapor deposition
      using dimethylethylamine:alane (DMEAA) as the precursor. It was shown that the
      transmission loss of the fiber with a 1.0-mm inner diameter was as low as 0.5
      dB/m for the fiber with 1.0-mm diameter when the bore of the fiber is pressurized
      with an inert gas to remove the absorption of air. When the fiber is bent at the
      radius of 30 cm, the additional loss was 1.6 dB.

PMID- 19404362
TI  - Editorial.
AB  - Validation-by-competition has arrived. Collaboration and incubation are next.
      This appears be the breakout year. I've mentioned previously the electronic
      publishing plans and projects of the Institute of Physics in the U.K., of the
      American Acoustical Society and of the American Physical Society. As of July 1,
      2000, all of them will have in operation free-standing, all-electronic, peer
      reviewed journals. The New Journal of Physics, Acoustic Research Letters Online,
      and Special Topics - Accelerators and Beams, respectively, are the names of these
      competitors of Optics Express. They go by the acronyms NJP, ARLO and STAB.

PMID- 19404363
TI  - Effects of optical layer impairments on 2.5 Gb/s optical CDMA transmission.
AB  - We conducted a computer simulation study to assess the effects of optical layer
      impairments on optical CDMA (O-CDMA) transmission of 8 asynchronous users at 2.5
      Gb/s each user over a 214-km link. It was found that with group velocity
      dispersion compensation, two other residual effects, namely, the nonzero
      chromatic dispersion slope of the single mode fiber (which causes skew) and the
      non-uniform EDFA gain (which causes interference power level to exceed signal
      power level of some codes) degrade the signal to multi-access interference (MAI)
      ratio. In contrast, four wave mixing and modulation due to the Kerr and Raman
      contributions to the fiber nonlinear refractive index are less important. Current
      wavelength-division multiplexing (WDM) technologies, including dispersion
      management, EDFA gain flattening, and 3 rd order dispersion compensation, are
      sufficient to overcome the impairments to the O-CDMA transmission system that we
      considered.

PMID- 19404364
TI  - Coaxial periodic optical waveguide.
AB  - Guided modes in a dielectric waveguide structure with a coaxial periodic multi
      layer are investigated by using a matrix formula with Bessel functions. We show
      that guided modes exist in the structure, and that the field is confined in the
      core which consists of the optically thinner medium. The dispersion curves are
      discontinuous, so that the modes can exist only in particular wavelength bands
      corresponding to the stop bands of the periodic structure of the clad. It is
      possible that the waveguide structure can be applied to filters or optical fibers
      to reduce nonlinear effects.

PMID- 19404365
TI  - Deep subsurface imaging in tissues using spectral and polarization filtering.
AB  - Deep subsurface imaging in tissues is demonstrated by employing both spectral and
      polarization discrimination of the backscattered photons. This technique provides
      enhancement in the visibility of subsurface structures via processing of the
      depolarized images obtained using polarized illumination at different
      wavelengths. The experimental results demonstrate detection and imaging of a high
      scattering object located up to 1.5-cm beneath the surface of a host chicken
      tissue used as the model medium.

PMID- 19404366
TI  - Directional correlation in direct and sequential double ionization of model
      atoms.
AB  - We discuss directional dependence in the time development of spatial
      wavefunctions, which includes jet formation, for two-electron model atoms exposed
      to intense laser fields. Two competing scenarios for double ionization are
      evident: (1) both electrons emerge simultaneously from the core region and on the
      same side of the nucleus, and (2) the electrons detach on opposite sides but not
      simultaneously. The importance of the electron-electron repulsion contribution to
      the competing processes is investigated for various laser intensities.

PMID- 19404367
TI  - Introduction.
AB  - Laser techniques for micromachining and other forms of material processing, such
      as texturing, scribing and surface cleaning, have been moving into industrial
      processes increasingly over the past few years. The recent advances in
      femtosecond laser micromachining have prompted a lively debate, both in the
      literature and at international conferences, on the subject of the most
      appropriate type of laser to carry out these processes in the industrial
      environment, whilst bearing in mind the importance to industrial users of
      ruggedness, reliability, cost and speed, as well as the quality of the finished
      part. Some of the protagonists in this debate have accepted invitations to
      contribute papers to this Focus Issue of Optics Express.

PMID- 19404368
TI  - Sub-diffraction limited structuring of solid targets with femtosecond laser
      pulses.
AB  - Possibilities to produce sub-diffraction limited structures in thin metal films
      and bulk dielectric materials using femtosecond laser pulses are investigated.
      The physics of ultrashort pulse laser ablation of solids is outlined. Results on
      the fabrication of sub-micrometer structures in 100-200 nm chrome-coated surfaces
      by direct ablative writing are reported. Polarization maintaining optical
      waveguides produced by femtosecond laser pulses inside crystalline quartz are
      demonstrated.

PMID- 19404369
TI  - Micro-ablation with high power pulsed copper vapor lasers.
AB  - Visible and UV lasers with nanosecond pulse durations, diffraction-limited beam
      quality and high pulse repetition rates have demonstrated micro-ablation in a
      wide variety of materials with sub-micron precision and sub-micron-sized heat
      affected zones. The copper vapour laser (CVL) is one of the important industrial
      lasers for micro-ablation applications. Manufacturing applications for the CVL
      include orifice drilling in fuel injection components and inkjet printers, micro
      milling of micromoulds, via hole drilling in printed circuit boards and silicon
      machining. Recent advances in higher power (100W visible, 5W UV), diffraction
      limited, compact CVLs are opening new possibilities for manufacturing with this
      class of nanosecond laser.

PMID- 19404370
TI  - Industrial applications of laser micromachining.
AB  - The use of pulsed lasers for microprocessing material in several manufacturing
      industries is presented. Microvia, ink jet printer nozzle and biomedical catheter
      hole drilling, thin-film scribing and micro-electro-mechanical system (MEMS)
      fabrication applications are reviewed.

PMID- 19404371
TI  - Laser removal of oxides and particles from copper surfaces for microelectronic
      fabrication.
AB  - Laser removal of surface oxides and small particles from copper surfaces was
      carried out using a Q-switched Nd:YAG laser. Oxide layers and small particles on
      copper surfaces should be removed for the improvement of solder quality on
      printed circuit boards (PCBs) and for the prevention of circuit failure or loss
      of production yield during the fabrication of microelectronic devices. A
      selective removal of surface oxides from a copper surface was achieved by the
      laser treatment, which was confirmed by on-line acoustic monitoring of the
      process. An angular laser cleaning technique in which the laser irradiates the
      surface at a glancing angle was used for effective removal of the particles from
      the surface. The unique characteristics of this technique and the cleaning
      mechanism are discussed.

PMID- 19404372
TI  - Focusing of high numerical aperture cylindrical-vector beams.
AB  - Cylindrical-vector beams are of increasing recent interest for their role in
      novel laser resonators and their applications to electron acceleration and
      scanning microscopy. In this paper, we calculate cylindrical-vector fields, near
      the focal region of an aplanatic lens, and briefly discuss some applications. We
      show that, in the particular case of a tightly focused, radially polarized beam,
      the polarization shows large inhomogeneities in the focal region, while the
      azimuthally polarized beam is purely transverse even at very high numerical
      apertures.

PMID- 19404373
TI  - Bending-induced colouring in a photonic crystal fibre.
AB  - A photonic crystal fibre has been fabricated with a photonic crystal that is
      surrounded by a number of silica cores. Bending of the fibre induces an
      interaction between the core and photonic crystal areas, resulting in a highly
      wavelength-dependent loss of the core modes. White-light transmission experiments
      are presented which show that the colour of the transmitted light changes as a
      function of the fibre-bending radius. We compare the results to a simple model
      and find agreement.

PMID- 19404374
TI  - Multiply scattered light tomography and confocal imaging: detecting
      neovascularization in age-related macular degeneration.
AB  - A novel technique, Multiply Scattered Light Tomography (MSLT), and confocal
      Infrared Imaging are used to provide diagnostic information using a comfortable,
      rapid, and noninvasive method. We investigated these techniques in detecting
      neovascularization in age-related macular degeneration. The MSLT used a Vertical
      Cavity Surface Emitting Laser (VCSEL) at 850 nm, while the confocal imaging
      technique used either the VCSEL or a 790 nm laser diode. Both were implemented
      into the topographical scanning system (TopSS, Laser Diagnostic Technologies,
      Inc.) Confocal imaging with both lasers provided different information about
      neovascularization as a function of focal plane, and different also from MSLT.

PMID- 19404375
TI  - Separation of coherent and incoherent nonlinearities in a heterodyne pump-probe
      experiment.
AB  - We demonstrate that the transient coherent nonlinearity (coherent artifact)
      affecting the pump-probe response of semiconductor optical amplifiers can be
      experimentally separated from the incoherent transient. The technique is based on
      measuring the mirror component of the coherent artifact which is a background
      free four--wave mixing signal at a different frequency with respect to the
      transmitted probe in a heterodyne detection scheme. Measurements on amplifiers of
      different length reveal strong deviations from the commonly expected symmetric
      shape of the coherent artifact in case of long waveguides.

PMID- 19404376
TI  - Experimental and scalar beam propagation analysis of an air-silica microstructure
      fiber.
AB  - We study the higher order guided modes in an air-silica microstructure fiber
      comprising a ring of six large air-holes surrounding a Germanium doped core. We
      characterize the modes experimentally using an intra-core Bragg grating. The
      experimentally observed modes are then accurately modeled by beam propagation
      simulations using an index profile similar to the observed fiber cross section.
      Theory and experiment confirm the presence of "inner cladding" modes with
      approximate cylindrical symmetry near the core, similar to conventional cladding
      modes, but which strongly exhibit the symmetry of the microstructure at large
      radius. Such modes are useful in fabricating robust tunable grating filters and
      we show that the Bragg grating is a useful diagnostic to measure their effective
      indices and intensity profiles.

PMID- 19404377
TI  - Near-field localization of ultrashort optical pulses in transverse 1-D periodic
      nanostructures.
AB  - We present a transverse 1-D periodic nanostructure which exhibits lateral
      internal Thorneld localization for normally incident ultrashort pulses, and which
      may be applied to the enhancement of nonlinear optical phenomena. The peak
      intensity of an optical pulse propagating in the nanostructure is approximately
      12 times that of an identical incident pulse propagating in a bulk material of
      the same refractive index. For second harmonic generation, an overall enhancement
      factor of approximately 10.8 is predicted. Modeling of pulse propagation is
      performed using Fourier spectrum decomposition and Rigorous Coupled-Wave Analysis
      (RCWA).

PMID- 19404378
TI  - The impact on the reflectance in VIS of a type of crude oil film floating on the
      water surface.
AB  - This paper reports the reflective features of a water surface covered with an oil
      film expressed by the dependence of the reflectance on the angle of light
      incidence and wavelength a nd film thickness with respect to downward and upward
      light fluxes. The sensitivity of the shape of these functions on the oil type
      appears especially strong in case of the upward light fluxes as opposed to
      downward fluxes.

PMID- 19404379
TI  - High-sensitivity pulse spectrogram measurement using two-photon absorption in a
      semiconductor at 1.5-microm wavelength.
AB  - A femtosecond pulse characterization technique is developed using frequency
      resolved optical gating based on the two-photon absorption in an InP crystal.The
      technique provides direct visual monitoring of pulse frequency chirping in the
      time-spectral domain for femtosecond pulses with a pulse energy as low as 3.8
      pJ.Pulse chirping and pedestal wings of 10-GHz optical fiber solitons are
      characterized experimentally for the first time by this technique.

PMID- 19404380
TI  - Diffractive optical elements with continuous relief fabricated by focused ion
      beam for monomode fiber coupling.
AB  - The design, microfabrication and testing of diffractive optical elements (DOE's)
      with continuous relief used for fiber coupling are discussed in detail. DOE's
      with diameters as small as 50 mm are fabricated by means of focused ion beam
      (FIB) technology. A focused Ga+ ion beam is used to mill a continuous relief
      microstructure at a 50 kV acceleration voltage. The optical performance of DOE's
      made in this way was compared with that of DOE's fabricated by other methods. The
      focusing performance of DOE's fabricated with three and six annulus by FIB
      milling was investigated. Testing of the system which has a coupling efficiency
      of -1.25 dB (75%) shows that the design meets the application's requirement for
      fiber coupling, and that DOE's manufactured by our FIB technology are
      practicable. Compared with a conventional fiber coupling system that uses a plano
      - convex lens, our system has the advantages of simplicity, short focal length,
      low cost for the lens and high coupling efficiency.

PMID- 19404381
TI  - Inversionless gain in an optically-dense resonant Doppler-broadened medium.
AB  - Resonant nonlinear-optical interference processes in four-level Doppler-broadened
      media are studied. Specific features of amplification and optical switching of
      short-wavelength radiation in a strongly-absorbing resonant gas under coherent
      quantum control with two longer wavelength radiations, are investigated. The
      major outcomes are illustrated with virtual experiments aimed at inversionless
      short-wavelength amplification, which also address deficiencies in this regard in
      recent experiments. With numerical simulations related to the proposed experiment
      in optically-dense sodium dimer vapor, we show optimal condition for optical
      switching and the expected gain of the probe radiation, which is above the
      oscillation threshold.

PMID- 19404382
TI  - Intramolecular Homolytic Aromatic Substitution of Alkyl 2-Benzimidazolyl Sulfones
      as a Means of Entry into Alkyl Radicals for Organic Synthesis.
AB  - The intramolecular radical aromatic substitution of heteroaryl sulfones by
      tethered aryl radicals has been investigated as a source of alkyl radicals. The 1
      (2-iodobenzyl)benzimidazole-2-sulfonyl system was found to be the most effective,
      while a tetrazole-based system did not undergo the desired radical aromatic
      substitution at all. Application of the benzimidazole-based system to the
      generation of alkyl radical and their subsequent use in radical cyclizations was
      demonstrated.

PMID- 19404383
TI  - Intervention in context-sensitive probabilistic Boolean networks revisited.
AB  - An approximate representation for the state space of a context-sensitive
      probabilistic Boolean network has previously been proposed and utilized to devise
      therapeutic intervention strategies. Whereas the full state of a context
      sensitive probabilistic Boolean network is specified by an ordered pair composed
      of a network context and a gene-activity profile, this approximate representation
      collapses the state space onto the gene-activity profiles alone. This reduction
      yields an approximate transition probability matrix, absent of context, for the
      Markov chain associated with the context-sensitive probabilistic Boolean network.
      As with many approximation methods, a price must be paid for using a reduced
      model representation, namely, some loss of optimality relative to using the full
      state space. This paper examines the effects on intervention performance caused
      by the reduction with respect to various values of the model parameters. This
      task is performed using a new derivation for the transition probability matrix of
      the context-sensitive probabilistic Boolean network. This expression of
      transition probability distributions is in concert with the original definition
      of context-sensitive probabilistic Boolean network. The performance of optimal
      and approximate therapeutic strategies is compared for both synthetic networks
      and a real case study. It is observed that the approximate representation
      describes the dynamics of the context-sensitive probabilistic Boolean network
      through the instantaneously random probabilistic Boolean network with similar
      parameters.

PMID- 19404384
TI  - Local control of excitation-contraction coupling in human embryonic stem cell
      derived cardiomyocytes.
AB  - We investigated the mechanisms of excitation-contraction (EC) coupling in human
      embryonic stem cell-derived cardiomyocytes (hESC-CMs) and fetal ventricular
      myocytes (hFVMs) using patch-clamp electrophysiology and confocal microscopy. We
      tested the hypothesis that Ca(2+) influx via voltage-gated L-type Ca(2+) channels
      activates Ca(2+) release from the sarcoplasmic reticulum (SR) via a local control
      mechanism in hESC-CMs and hFVMs. Field-stimulated, whole-cell [Ca(2+)](i)
      transients in hESC-CMs required Ca(2+) entry through L-type Ca(2+) channels, as
      evidenced by the elimination of such transients by either removal of
      extracellular Ca(2+) or treatment with diltiazem, an L-type channel inhibitor.
      Ca(2+) release from the SR also contributes to the [Ca(2+)](i) transient in these
      cells, as evidenced by studies with drugs interfering with either SR Ca(2+)
      release (i.e. ryanodine and caffeine) or reuptake (i.e. thapsigargin and
      cyclopiazonic acid). As in adult ventricular myocytes, membrane depolarization
      evoked large L-type Ca(2+) currents (I(Ca)) and corresponding whole-cell
      [Ca(2+)](i) transients in hESC-CMs and hFVMs, and the amplitude of both I(Ca) and
      the [Ca(2+)](i) transients were finely graded by the magnitude of the
      depolarization. hESC-CMs exhibit a decreasing EC coupling gain with
      depolarization to more positive test potentials, "tail" [Ca(2+)](i) transients
      upon repolarization from extremely positive test potentials, and co-localized
      ryanodine and sarcolemmal L-type Ca(2+) channels, all findings that are
      consistent with the local control hypothesis. Finally, we recorded Ca(2+) sparks
      in hESC-CMs and hFVMs. Collectively, these data support a model in which tight,
      local control of SR Ca(2+) release by the I(Ca) during EC coupling develops early
      in human cardiomyocytes.

PMID- 19404385
TI  - Ambient air pollution and birth defects in brisbane, australia.
AB  - BACKGROUND: Birth defects are a major public health concern as they are the
      leading cause of neonatal and infant mortality. Observational studies have linked
      environmental pollution to adverse birth outcomes, including congenital
      anomalies. This study examined potential associations between ambient air
      pollution and congenital heart defects and cleft lip or palate among births in
      Brisbane, Australia (1998-2004). METHODS: Ambient air pollution levels were
      averaged over weeks 3-8 of pregnancy among 150,308 births. Using a case-control
      design, we used conditional logistic regression and matched cases to 5 controls.
      Analyses were conducted using all births, and then births where the mother
      resided within 6 and 12 kilometers of an ambient air quality monitor. FINDINGS:
      When analyzing all births there was no indication that ambient air pollution in
      Brisbane was associated with a higher risk of cardiac defects. Among births where
      the mother resided within 6 kilometers of an ambient air quality monitor, a 5 ppb
      increase in O(3) was associated with an increased risk of pulmonary artery and
      valve defects (OR 2.96, 95% CI: 1.34, 7.52) while a 0.6 ppb increase in SO(2) was
      associated with an increased risk of aortic artery and valve defects (OR 10.76,
      95% CI: 1.50, 179.8). For oral cleft defects among all births, the only adverse
      association was between SO(2) and cleft lip with or without cleft palate (OR
      1.27, 95% CI: 1.01, 1.62). However, various significant inverse associations were
      also found between air pollutants and birth defects. CONCLUSIONS: This study
      found mixed results and it is difficult to conclude whether ambient air pollution
      in Brisbane has an adverse association with the birth defects examined. Studies
      using more detailed estimates of air pollution exposure are needed.

PMID- 19404386
TI  - Comparative component analysis of exons with different splicing frequencies.
AB  - Transcriptional isoforms are not just random combinations of exons. What has
      caused exons to be differentially spliced and whether exons with different
      splicing frequencies are subjected to divergent regulation by potential elements
      or splicing signals? Beyond the conventional classification for alternatively
      spliced exons (ASEs) and constitutively spliced exons (CSEs), we have classified
      exons from alternatively spliced human genes and their mouse orthologs (12,314
      and 5,464, respectively) into four types based on their splicing frequencies.
      Analysis has indicated that different groups of exons presented divergent
      compositional and regulatory properties. Interestingly, with the decrease of
      splicing frequency, exons tend to have greater lengths, higher GC content, and
      contain more splicing elements and repetitive elements, which seem to imply that
      the splicing frequency is influenced by such factors. Comparison of non
      alternatively spliced (NAS) mouse genes with alternatively spliced human
      orthologs also suggested that exons with lower splicing frequencies may be newly
      evolved ones which gained functions with splicing frequencies altered through the
      evolution. Our findings have revealed for the first time that certain factors may
      have critical influence on the splicing frequency, suggesting that exons with
      lower splicing frequencies may originate from old repetitive sequences, with
      splicing sites altered by mutation, gaining novel functions and become more
      frequently spliced.

PMID- 19404387
TI  - A conserved multi-gene family induces cross-reactive antibodies effective in
      defense against Plasmodium falciparum.
AB  - BACKGROUND: Two related merozoite surface proteins, MSP3 and MSP6, have
      previously been identified as targets of antibody-dependent cellular inhibition
      (ADCI), a protective mechanism against Plasmodium falciparum malaria. Both MSP3
      and MSP6 share a common characteristic small N-terminal signature amino-acid
      stretch (NLRNA/G), a feature similar to MSP3-like orthologs identified in other
      human and primate malaria parasites. METHODS/RESULTS: This signature amino-acid
      sequence led to the identification of eight ORFs contiguously located on P.
      falciparum chromosome 10. Our subsequent investigations on their expression,
      localization, sequence conservation, epitope sharing, immunogenicity and the
      functional role of antibodies in defense are reported here. Six members of P.
      falciparum MSP3-multigene family share similar sequence organization within their
      C-terminal regions, are simultaneously expressed as merozoite surface proteins
      and are highly conserved among parasite isolates. Each of these proteins is a
      target of naturally occurring antibodies effective at parasite killing in ADCI
      assays. Moreover, both naturally occurring antibodies and those generated by
      immunization display cross-reactivity with other members of the family and
      exhibit varied binding avidities. CONCLUSIONS/SIGNIFICANCE: The unusual
      characteristics of the MSP3 multi-gene family lead us to hypothesize that the
      simultaneous expression of targets eliciting cross-reactive antibody responses
      capable of controlling parasite densities could represent an immune process
      selected through evolution to maintain homeostasis between P. falciparum and
      human hosts; a process that allows the continuous transmission of the parasite
      without killing the host. Our observations also have practical consequences for
      vaccine development by suggesting MSP3 vaccine efficacy might be improved when
      combined with the various C-terminus regions of the MSP3 family members to
      generate a wider range of antibodies acting and to increase vaccine
      immunogenicity in varied human genetic backgrounds.

PMID- 19404388
TI  - Monomeric bistability and the role of autoloops in gene regulation.
AB  - Genetic toggle switches are widespread in gene regulatory networks (GRN).
      Bistability, namely the ability to choose among two different stable states, is
      an essential feature of switching and memory devices. Cells have many regulatory
      circuits able to provide bistability that endow a cell with efficient and
      reliable switching between different physiological modes of operation. It is
      often assumed that negative feedbacks with cooperative binding (i.e. the
      formation of dimers or multimers) are a prerequisite for bistability. Here we
      analyze the relation between bistability in GRN under monomeric regulation and
      the role of autoloops under a deterministic setting. Using a simple geometric
      argument, we show analytically that bistability can also emerge without
      multimeric regulation, provided that at least one regulatory autoloop is present.

PMID- 19404389
TI  - Can ethograms be automatically generated using body acceleration data from free
      ranging birds?
AB  - An ethogram is a catalogue of discrete behaviors typically employed by a species.
      Traditionally animal behavior has been recorded by observing study individuals
      directly. However, this approach is difficult, often impossible, in the case of
      behaviors which occur in remote areas and/or at great depth or altitude. The
      recent development of increasingly sophisticated, animal-borne data loggers, has
      started to overcome this problem. Accelerometers are particularly useful in this
      respect because they can record the dynamic motion of a body in e.g. flight,
      walking, or swimming. However, classifying behavior using body acceleration
      characteristics typically requires prior knowledge of the behavior of free
      ranging animals. Here, we demonstrate an automated procedure to categorize
      behavior from body acceleration, together with the release of a user-friendly
      computer application, "Ethographer". We evaluated its performance using
      longitudinal acceleration data collected from a foot-propelled diving seabird,
      the European shag, Phalacrocorax aristotelis. The time series data were converted
      into a spectrum by continuous wavelet transformation. Then, each second of the
      spectrum was categorized into one of 20 behavior groups by unsupervised cluster
      analysis, using k-means methods. The typical behaviors extracted were
      characterized by the periodicities of body acceleration. Each categorized
      behavior was assumed to correspond to when the bird was on land, in flight, on
      the sea surface, diving and so on. The behaviors classified by the procedures
      accorded well with those independently defined from depth profiles. Because our
      approach is performed by unsupervised computation of the data, it has the
      potential to detect previously unknown types of behavior and unknown sequences of
      some behaviors.

PMID- 19404390
TI  - Expression signatures of metastatic capacity in a genetic mouse model of lung
      adenocarcinoma.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is the foremost cause of cancer
      related death in Western countries, which is due partly to the propensity of
      NSCLC cells to metastasize. The biologic basis for NSCLC metastasis is not well
      understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we addressed this deficiency by
      transcriptionally profiling tumors from a genetic mouse model of human lung
      adenocarcinoma that develops metastatic disease owing to the expression of K
      ras(G12D) and p53(R172H). We identified 2,209 genes that were differentially
      expressed in distant metastases relative to matched lung tumors. Mining of
      publicly available data bases revealed this expression signature in a subset of
      NSCLC patients who had a poorer prognosis than those without the signature.
      CONCLUSIONS/SIGNIFICANCE: These findings provide evidence that K-ras(G12D);
      p53(R172H) mice recapitulate features of human NSCLC metastasis and will provide
      a useful platform on which to study the biologic basis for lung adenocarcinoma
      metastasis and its prevention by novel agents.

PMID- 19404391
TI  - A method to quantify mouse coat-color proportions.
AB  - Coat-color proportions and patterns in mice are used as assays for many processes
      such as transgene expression, chimerism, and epigenetics. In many studies, coat
      color readouts are estimated from subjective scoring of individual mice. Here we
      show a method by which mouse coat color is quantified as the proportion of coat
      shown in one or more digital images. We use the yellow-agouti mouse model of
      epigenetic variegation to demonstrate this method. We apply this method to live
      mice using a conventional digital camera for data collection. We use a raster
      graphics editing program to convert agouti regions of the coat to a standard,
      uniform, brown color and the yellow regions of the coat to a standard, uniform,
      yellow color. We use a second program to quantify the proportions of these
      standard colors. This method provides quantification that relates directly to the
      visual appearance of the live animal. It also provides an objective analysis with
      a traceable record, and it should allow for precise comparisons of mouse coats
      and mouse cohorts within and between studies.

PMID- 19404393
TI  - Polymorphism located between CPT1B and CHKB, and HLA-DRB1*1501-DQB1*0602
      haplotype confer susceptibility to CNS hypersomnias (essential hypersomnia).
AB  - BACKGROUND: SNP rs5770917 located between CPT1B and CHKB, and HLA-DRB1*1501
      DQB1*0602 haplotype were previously identified as susceptibility loci for
      narcolepsy with cataplexy. This study was conducted in order to investigate
      whether these genetic markers are associated with Japanese CNS hypersomnias
      (essential hypersomnia: EHS) other than narcolepsy with cataplexy. PRINCIPAL
      FINDINGS: EHS was significantly associated with SNP rs5770917 (P(allele) =
      3.6x10(-3); OR = 1.56; 95% c.i.: 1.12-2.15) and HLA-DRB1*1501-DQB1*0602 haplotype
      (P(positivity) = 9.2x10(-11); OR = 3.97; 95% c.i.: 2.55-6.19). No interaction
      between the two markers (SNP rs5770917 and HLA-DRB1*1501-DQB1*0602 haplotype) was
      observed in EHS. CONCLUSION: CPT1B, CHKB and HLA are candidates for
      susceptibility to CNS hypersomnias (EHS), as well as narcolepsy with cataplexy.

PMID- 19404392
TI  - Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2
      suppression to reduce HIV-1 transmission: the partners study.
AB  - BACKGROUND: The Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a
      phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2)
      suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to
      their HIV-1 susceptible partners, which requires recruitment of HIV-1
      serodiscordant heterosexual couples. We describe the baseline characteristics of
      this cohort. METHODS: HIV-1 serodiscordant heterosexual couples, in which the HIV
      1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and
      was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern
      Africa. Demographic, behavioral, clinical and laboratory characteristics were
      assessed. RESULTS: Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the
      HIV-1 infected partners were women. Couples had cohabitated for a median of 5
      years (range 2-9) with 28% reporting unprotected sex in the month prior to
      enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men
      were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted
      infections were uncommon (<5%), except for Trichomonas vaginalis in 14% of HIV-1
      infected women. Median baseline CD4 count for HIV-1 infected participants was
      462cells/mcL and median HIV-1 plasma RNA was 4.2 log(10) copies/mL. After
      adjusting for age and African region, correlates of HIV-1 RNA level included male
      gender (+0.24 log(10) copies/mL; p<0.001) and CD4 count (-0.25 and -0.55 log(10)
      copies/mL for CD4 350-499 and >500 relative to <350, respectively, p<0.001).
      CONCLUSIONS: The Partners Study successfully enrolled a cohort of 3408
      heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1
      transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir
      for HSV-2 suppression in preventing HIV-1 transmission and provide insights into
      biological and behavioral factors determining heterosexual HIV-1 transmission.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00194519.

PMID- 19404395
TI  - Cold induces micro- and nano-scale reorganization of lipid raft markers at mounds
      of T-cell membrane fluctuations.
AB  - Whether and how cold causes changes in cell-membrane or lipid rafts remain poorly
      characterized. Using the NSOM/QD and confocal imaging systems, we found that cold
      caused microscale redistribution of lipid raft markers, GM1 for lipid and CD59
      for protein, from the peripheral part of microdomains to the central part on
      Jurkat T cells, and that cold also induced the nanoscale size-enlargement (1/3-
      to 2/3-fold) of the nanoclusters of lipid raft markers and even the
      colocalization of GM1 and CD59 nanoclusters. These findings indicate cold-induced
      lateral rearrangement/coalescence of raft-related membrane heterogeneity. The
      cold-induced re-distribution of lipid raft markers under a nearly-natural
      condition provide clues for their alternations, and help to propose a model in
      which raft lipids associate themselves or interact with protein components to
      generate functional membrane heterogeneity in response to stimulus. The data also
      underscore the possible cold-induced artifacts in early-described cold-related
      experiments and the detergent-resistance-based analyses of lipid rafts at 4
      degrees C, and provide a biophysical explanation for recently-reported cold
      induced activation of signaling pathways in T cells. Importantly, our
      fluorescence-topographic NSOM imaging demonstrated that GM1/CD59 raft markers
      distributed and re-distributed at mounds but not depressions of T-cell membrane
      fluctuations. Such mound-top distribution of lipid raft markers or lipid rafts
      provides spatial advantage for lipid rafts or contact molecules interacting
      readily with neighboring cells or free molecules.

PMID- 19404394
TI  - CD133+ anaplastic thyroid cancer cells initiate tumors in immunodeficient mice
      and are regulated by thyrotropin.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most lethal human
      malignancies. Its rapid onset and resistance to conventional therapeutics
      contribute to a mean survival of six months after diagnosis and make the
      identification of thyroid-cancer-initiating cells increasingly important.
      METHODOLOGY/PRINCIPAL FINDINGS: In prior studies of ATC cell lines, CD133(+)
      cells exhibited stem-cell-like features such as high proliferation, self-renewal
      and colony-forming ability in vitro. Here we show that transplantation of
      CD133(+) cells, but not CD133(-) cells, into immunodeficient NOD/SCID mice is
      sufficient to induce growth of tumors in vivo. We also describe how the
      proportion of ATC cells that are CD133(+) increases dramatically over three
      months of culture, from 7% to more than 80% of the total. This CD133(+) cell pool
      can be further separated by flow cytometry into two distinct populations:
      CD133(+/high) and CD133(+/low). Although both subsets are capable of long-term
      tumorigenesis, the rapidly proliferating CD133(+/high) cells are by far the most
      efficient. They also express high levels of the stem cell antigen Oct4 and the
      receptor for thyroid stimulating hormone, TSHR. Treating ATC cells with TSH
      causes a three-fold increase in the numbers of CD133(+) cells and elicits a dose
      dependent up-regulation of the expression of TSHR and Oct4 in these cells. More
      importantly, immunohistochemical analysis of tissue specimens from ATC patients
      indicates that CD133 is highly expressed on tumor cells but not on neighboring
      normal thyroid cells. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is the
      first report indicating that CD133(+) ATC cells are solely responsible for tumor
      growth in immunodeficient mice. Our data also give a unique insight into the
      regulation of CD133 by TSH. These highly tumorigenic CD133(+) cells and the
      activated TSH signaling pathway may be useful targets for future ATC therapies.

PMID- 19404396
TI  - Domain swapping and different oligomeric States for the complex between
      calmodulin and the calmodulin-binding domain of calcineurin a.
AB  - BACKGROUND: Calmodulin (CaM) is a ubiquitously expressed calcium sensor that
      engages in regulatory interactions with a large number of cellular proteins.
      Previously, a unique mode of CaM target recognition has been observed in the
      crystal structure of a complex between CaM and the CaM-binding domain of
      calcineurin A. METHODOLOGY/PRINCIPAL FINDINGS: We have solved a high-resolution
      crystal structure of a complex between CaM and the CaM-binding domain of
      calcineurin A in a novel crystal form, which shows a dimeric assembly of
      calmodulin, as observed before in the crystal state. We note that the
      conformation of CaM in this complex is very similar to that of unliganded CaM,
      and a detailed analysis revels that the CaM-binding motif in calcineurin A is of
      a novel '1-11' type. However, using small-angle X-ray scattering (SAXS), we show
      that the complex is fully monomeric in solution, and a structure of a canonically
      collapsed CaM-peptide complex can easily be fitted into the SAXS data. This
      result is also supported by size exclusion chromatography, where the addition of
      the ligand peptide decreases the apparent size of CaM. In addition, we studied
      the energetics of binding by isothermal titration calorimetry and found them to
      closely resemble those observed previously for ligand peptides from CaM-dependent
      kinases. CONCLUSIONS/SIGNIFICANCE: Our results implicate that CaM can also form a
      complex with the CaM-binding domain of calcineurin in a 1 ratio 1 stoichiometry,
      in addition to the previously observed 2 ratio 2 arrangement in the crystal
      state. At the structural level, going from 2 ratio 2 association to two 1 ratio 1
      complexes will require domain swapping in CaM, accompanied by the characteristic
      bending of the central linker helix between the two lobes of CaM.

PMID- 19404397
TI  - Flotillins interact with PSGL-1 in neutrophils and, upon stimulation, rapidly
      organize into membrane domains subsequently accumulating in the uropod.
AB  - BACKGROUND: Neutrophils polarize and migrate in response to chemokines. Different
      types of membrane microdomains (rafts) have been postulated to be present in rear
      and front of polarized leukocytes and disruption of rafts by cholesterol
      sequestration prevents leukocyte polarization. Reggie/flotillin-1 and -2 are two
      highly homologous proteins that are ubiquitously enriched in detergent resistant
      membranes and are thought to shape membrane microdomains by forming homo- and
      hetero-oligomers. It was the goal of this study to investigate dynamic membrane
      microdomain reorganization during neutrophil activation. METHODOLOGY/PRINCIPAL
      FINDINGS: We show now, using immunofluorescence staining and co
      immunoprecipitation, that endogenous flotillin-1 and -2 colocalize and associate
      in resting spherical and polarized primary neutrophils. Flotillins redistribute
      very early after chemoattractant stimulation, and form distinct caps in more than
      90% of the neutrophils. At later time points flotillins accumulate in the uropod
      of polarized cells. Chemotactic peptide-induced redistribution and capping of
      flotillins requires integrity and dynamics of the actin cytoskeleton, but does
      not involve Rho-kinase dependent signaling related to formation of the uropod.
      Both flotillin isoforms are involved in the formation of this membrane domain, as
      uropod location of exogenously expressed flotillins is dramatically enhanced by
      co-overexpression of tagged flotillin-1 and -2 in differentiated HL-60 cells as
      compared to cells expressing only one tagged isoform. Flotillin-1 and -2
      associate with P-selectin glycoprotein ligand 1 (PSGL-1) in resting and in
      stimulated neutrophils as shown by colocalization and co-immunoprecipitation.
      Neutrophils isolated from PSGL-1-deficient mice exhibit flotillin caps to the
      same extent as cells isolated from wild type animals, implying that PSGL-1 is not
      required for the formation of the flotillin caps. Finally we show that stimulus
      dependent redistribution of other uropod-located proteins, CD43 and
      ezrin/radixin/moesin, occurs much slower than that of flotillins and PSGL-1.
      CONCLUSIONS/SIGNIFICANCE: These results suggest that flotillin-rich actin
      dependent membrane microdomains are importantly involved in neutrophil uropod
      formation and/or stabilization and organize uropod localization of PSGL-1.

PMID- 19404398
TI  - Inorganic polyphosphate modulates TRPM8 channels.
AB  - Polyphosphate (polyP) is an inorganic polymer built of tens to hundreds of
      phosphates, linked by high-energy phosphoanhydride bonds. PolyP forms complexes
      and modulates activities of many proteins including ion channels. Here we
      investigated the role of polyP in the function of the transient receptor
      potential melastatin 8 (TRPM8) channel. Using whole-cell patch-clamp and
      fluorescent calcium measurements we demonstrate that enzymatic breakdown of polyP
      by exopolyphosphatase (scPPX1) inhibits channel activity in human embryonic
      kidney and F-11 neuronal cells expressing TRPM8. We demonstrate that the TRPM8
      channel protein is associated with polyP. Furthermore, addition of scPPX1 altered
      the voltage-dependence and blocked the activity of the purified TRPM8 channels
      reconstituted into planar lipid bilayers, where the activity of the channel was
      initiated by cold and menthol in the presence of phosphatidylinositol 4,5
      biphosphate (PtdIns(4,5)P(2)). The biochemical analysis of the TRPM8 protein also
      uncovered the presence of poly-(R)-3-hydroxybutyrate (PHB), which is frequently
      associated with polyP. We conclude that the TRPM8 protein forms a stable complex
      with polyP and its presence is essential for normal channel activity.

PMID- 19404399
TI  - The influence of clinical information in the histopathologic diagnosis of
      melanocytic skin neoplasms.
AB  - BACKGROUND: We tested the relevance of clinical information in the
      histopathologic evaluation of melanocytic skin neoplasm (MSN). METHODS:
      Histopathologic specimens from 99 clinically atypical MSN were circulated among
      ten histopathologists; each case had clinical information available in a database
      with a five-step procedure (no information; age/sex/location; clinical diagnosis;
      clinical image; dermoscopic image); each step had a histopathologic diagnosis (D1
      through D5); each diagnostic step had a level of diagnostic confidence (LDC)
      ranging from 1 (no diagnostic certainty) to 5 (absolute diagnostic certainty).
      The comparison of the LDC was employed with an analysis of variance (ANOVA) for
      repeated measures. FINDINGS: In D1 (no information), 36/99 cases (36.3%) had
      unanimous diagnosis; in D5 (full information available), 51/99 cases (51.5%) had
      unanimous diagnosis (p for difference between proportions <0.001). The observer
      agreement expressed as kappa increased significantly from D1 to D5. The mean LDC
      linearly increased for each observer from D1 through D5 (p for linear trend
      <0.001). On average, each histopathologist changed his initial diagnosis in 7
      cases (range: 2-23). Most diagnostic changes were in D2 (age/sex/location).
      INTERPRETATION: The histopathologic criteria for the diagnosis of MSN can work as
      such, but the final histopathologic diagnosis is a clinically-aided
      interpretation. Clinical data sometimes reverse the initial histopathologic
      evaluation.

PMID- 19404401
TI  - Muscle mitochondrial uncoupling dismantles neuromuscular junction and triggers
      distal degeneration of motor neurons.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS), the most frequent adult onset
      motor neuron disease, is associated with hypermetabolism linked to defects in
      muscle mitochondrial energy metabolism such as ATP depletion and increased oxygen
      consumption. It remains unknown whether muscle abnormalities in energy metabolism
      are causally involved in the destruction of neuromuscular junction (NMJ) and
      subsequent motor neuron degeneration during ALS. METHODOLOGY/PRINCIPAL FINDINGS:
      We studied transgenic mice with muscular overexpression of uncoupling protein 1
      (UCP1), a potent mitochondrial uncoupler, as a model of muscle restricted
      hypermetabolism. These animals displayed age-dependent deterioration of the NMJ
      that correlated with progressive signs of denervation and a mild late-onset motor
      neuron pathology. NMJ regeneration and functional recovery were profoundly
      delayed following injury of the sciatic nerve and muscle mitochondrial uncoupling
      exacerbated the pathology of an ALS animal model. CONCLUSIONS/SIGNIFICANCE: These
      findings provide the proof of principle that a muscle restricted mitochondrial
      defect is sufficient to generate motor neuron degeneration and suggest that
      therapeutic strategies targeted at muscle metabolism might prove useful for motor
      neuron diseases.

PMID- 19404400
TI  - Complex evolution of a Y-chromosomal double homeobox 4 (DUX4)-related gene family
      in hominoids.
AB  - The human Y chromosome carries four human Y-chromosomal
      euchromatin/heterochromatin transition regions, all of which are characterized by
      the presence of interchromosomal segmental duplications. The Yq11.1/Yq11.21
      transition region harbours a peculiar segment composed of an imperfectly
      organized tandem-repeat structure encoding four members of the double homeobox
      (DUX) gene family. By comparative fluorescence in situ hybridization (FISH)
      analysis we have documented the primary appearance of Y-chromosomal DUX genes
      (DUXY) on the gibbon Y chromosome. The major amplification and dispersal of DUXY
      paralogs occurred after the gibbon and hominid lineages had diverged. Orthologous
      DUXY loci of human and chimpanzee show a highly similar structural organization.
      Sequence alignment survey, phylogenetic reconstruction and recombination
      detection analyses of human and chimpanzee DUXY genes revealed the existence of
      all copies in a common ancestor. Comparative analysis of the circumjacent beta
      satellites indicated that DUXY genes and beta-satellites evolved in concert.
      However, evolutionary forces acting on DUXY genes may have induced amino acid
      sequence differences in the orthologous chimpanzee and human DUXY open reading
      frames (ORFs). The acquisition of complete ORFs in human copies might relate to
      evolutionary advantageous functions indicating neo-functionalization. We propose
      an evolutionary scenario in which an ancestral tandem array DUX gene cassette
      transposed to the hominoid Y chromosome followed by lineage-specific chromosomal
      rearrangements paved the way for a species-specific evolution of the Y
      chromosomal members of a large highly diverged homeobox gene family.

PMID- 19404402
TI  - A novel fibronectin binding motif in MSCRAMMs targets F3 modules.
AB  - BACKGROUND: BBK32 is a surface expressed lipoprotein and fibronectin (Fn)-binding
      microbial surface component recognizing adhesive matrix molecule (MSCRAMM) of
      Borrelia burgdorferi, the causative agent of Lyme disease. Previous studies from
      our group showed that BBK32 is a virulence factor in experimental Lyme disease
      and located the Fn-binding region to residues 21-205 of the lipoprotein.
      METHODOLOGY/PRINCIPAL FINDINGS: Studies aimed at identifying interacting sites
      between BBK32 and Fn revealed an interaction between the MSCRAMM and the Fn F3
      modules. Further analysis of this interaction showed that BBK32 can cause the
      aggregation of human plasma Fn in a similar concentration-dependent manner to
      that of anastellin, the superfibronectin (sFn) inducing agent. The resulting Fn
      aggregates are conformationally distinct from plasma Fn as indicated by a change
      in available thermolysin cleavage sites. Recombinant BBK32 and anastellin affect
      the structure of Fn matrices formed by cultured fibroblasts and inhibit
      endothelial cell proliferation similarly. Within BBK32, we have located the sFn
      forming activity to a region between residues 160 and 175 which contains two
      sequence motifs that are also found in anastellin. Synthetic peptides mimicking
      these motifs induce Fn aggregation, whereas a peptide with a scrambled sequence
      motif was inactive, suggesting that these motifs represent the sFn-inducing
      sequence. CONCLUSIONS/SIGNIFICANCE: We conclude that BBK32 induces the formation
      of Fn aggregates that are indistinguishable from those formed by anastellin. The
      results of this study provide evidence for how bacteria can target host proteins
      to manipulate host cell activities.

PMID- 19404403
TI  - A vault nanoparticle vaccine induces protective mucosal immunity.
AB  - BACKGROUND: Generation of robust cell-mediated immune responses at mucosal
      surfaces while reducing overall inflammation is a primary goal for vaccination.
      Here we report the use of a recombinant nanoparticle as a vaccine delivery
      platform against mucosal infections requiring T cell-mediated immunity for
      eradication. METHODOLOGY/PRINCIPAL FINDINGS: We encapsulated an immunogenic
      protein, the major outer membrane protein (MOMP) of Chlamydia muridarum, within
      hollow, vault nanocapsules (MOMP-vaults) that were engineered to bind IgG for
      enhanced immunity. Intranasal immunization (i.n) with MOMP-vaults induced anti
      chlamydial immunity plus significantly attenuated bacterial burden following
      challenge infection. Vault immunization induced anti-chlamydial immune responses
      and inflammasome formation but did not activate toll-like receptors. Moreover,
      MOMP-vault immunization enhanced microbial eradication without the inflammation
      usually associated with adjuvants. CONCLUSIONS/SIGNIFICANCE: Vault nanoparticles
      containing immunogenic proteins delivered to the respiratory tract by the i.n.
      route can act as "smart adjuvants" for inducing protective immunity at distant
      mucosal surfaces while avoiding destructive inflammation.

PMID- 19404404
TI  - A molecular function map of Ewing's sarcoma.
AB  - BACKGROUND: EWS-FLI1 is a chimeric ETS transcription factor that is, due to a
      chromosomal rearrangement, specifically expressed in Ewing's sarcoma family
      tumors (ESFT) and is thought to initiate the development of the disease. Previous
      genomic profiling experiments have identified EWS-FLI1-regulated genes and genes
      that discriminate ESFT from other sarcomas, but so far a comprehensive analysis
      of EWS-FLI1-dependent molecular functions characterizing this aggressive cancer
      is lacking. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a molecular function
      map of ESFT was constructed based on an integrative analysis of gene expression
      profiling experiments following EWS-FLI1 knockdown in a panel of five ESFT cell
      lines, and on gene expression data from the same platform of 59 primary ESFT. Out
      of 80 normal tissues tested, mesenchymal progenitor cells (MPC) were found to fit
      the hypothesis that EWS-FLI1 is the driving transcriptional force in ESFT best
      and were therefore used as the reference tissue for the construction of the
      molecular function map. The interrelations of molecular pathways were visualized
      by measuring the similarity among annotated gene functions by gene sharing. The
      molecular function map highlighted distinct clusters of activities for EWS-FLI1
      regulated genes in ESFT and revealed a striking difference between EWS-FLI1 up-
      and down-regulated genes: EWS-FLI1 induced genes mainly belong to cell cycle
      regulation, proliferation, and response to DNA damage, while repressed genes were
      associated with differentiation and cell communication. CONCLUSIONS/SIGNIFICANCE:
      This study revealed that EWS-FLI1 combines by distinct molecular mechanisms two
      important functions of cellular transformation in one protein, growth promotion
      and differentiation blockage. By taking MPC as a reference tissue, a significant
      EWS-FLI1 signature was discovered in ESFT that only partially overlapped with
      previously published EWS-FLI1-dependent gene expression patterns, identifying a
      series of novel targets for the chimeric protein in ESFT. Our results may guide
      target selection for future ESFT specific therapies.

PMID- 19404405
TI  - Angiotensin-(1-7) and the g protein-coupled receptor MAS are key players in renal
      inflammation.
AB  - Angiotensin (Ang) II mediates pathophysiologial changes in the kidney. Ang-(1-7)
      by interacting with the G protein-coupled receptor Mas may also have important
      biological activities.In this study, renal deficiency for Mas diminished renal
      damage in models of renal insufficiency as unilateral ureteral obstruction and
      ischemia/reperfusion injury while the infusion of Ang-(1-7) to wild-type mice
      pronounced the pathological outcome by aggravating the inflammatory response. Mas
      deficiency inhibited NF-kappaB activation and thus the elevation of inflammation
      stimulating cytokines, while Ang-(1-7) infusion had proinflammatory properties in
      experimental models of renal failure as well as under basal conditions. The Ang
      (1-7)-mediated NF-kappaB activation was Mas dependent but did not involve Ang II
      receptors. Therefore, the blockade of the NF-kappaB-activating properties of the
      receptor Mas could be a new strategy in the therapy of failing kidney.

PMID- 19404406
TI  - Tubulin tyrosination is required for the proper organization and pathfinding of
      the growth cone.
AB  - BACKGROUND: During development, neuronal growth cones integrate diffusible and
      contact guidance cues that are conveyed to both actin and microtubule (MT)
      cytoskeletons and ensure axon outgrowth and pathfinding. Although several post
      translational modifications of tubulin have been identified and despite their
      strong conservation among species, their physiological roles during development,
      especially in the nervous sytem, are still poorly understood.
      METHODOLOGY/FINDINGS: Here, we have dissected the role of a post-translational
      modification of the last amino acid of the alpha-tubulin on axonal growth by
      analyzing the phenotype of precerebellar neurons in Tubulin tyrosin ligase knock
      out mice (TTL(-/-)) through in vivo, ex vivo and in vitro analyses. TTL(-/-)
      neurons are devoid of tyrosinated tubulin. Their pathway shows defects in vivo,
      ex vivo, in hindbrains open-book preparations or in vitro, in a collagen matrix.
      Their axons still orient toward tropic cues, but they emit supernumerary branches
      and their growth cones are enlarged and exhibit an emission of mis-oriented
      filopodia. Further analysis of the TTL(-/-) growth cone intracellular
      organization also reveals that the respective localization of actin and MT
      filaments is disturbed, with a decrease in the distal accumulation of Myosin IIB,
      as well as a concomitant Rac1 over-activation in the hindbrain. Pharmacological
      inhibition of Rac1 over-activation in TTL(-/-) neurons can rescue Myosin IIB
      localization. CONCLUSIONS/SIGNIFICANCE: In the growth cone, we propose that
      tubulin tyrosination takes part in the relative arrangement of actin and MT
      cytoskeletons, in the regulation of small GTPases activity, and consequently, in
      the proper morphogenesis, organization and pathfinding of the growth cone during
      development.

PMID- 19404408
TI  - A population-based clinical trial of irinotecan and Carboplatin.
AB  - Purpose. Phase I trials of anticancer drugs are commonly conducted using the
      method of modified Fibonacci. We have developed a population-based design for
      phase I trials of combining anticancer drugs such as irinotecan and carboplatin.
      Patients and Methods. Intrapatient dose escalation of irinotecan and carboplatin
      was performed according to a predetermined schema to reach individual dose
      limiting toxicity (DLT) in 50 patients with solid tumors refractory to previous
      chemotherapy. The individual toxicity-limiting dose levels were analyzed for
      normal distribution using the method of Ryan-Joiner and subsequently used to
      determine a population-based maximum tolerated dose (pMTD). For comparison, a
      simulation study was performed using the method of modified Fibonacci. Results.
      The most common dose-limiting toxicities (DLTs) included neutropenia (58%),
      thrombocytopenia (16%), and diarrhea (8%). The frequency of individual toxicity
      limiting dose levels of 50 patients approximated a normal distribution. The dose
      levels associated with individual limiting toxicities ranged from level 1
      (irinotecan 100 mg/m(2) and carboplatin AUC = 4 mg/mL x min) to level 8
      (irinotecan 350 mg/m(2) and carboplatin AUC = 6). The pMTD was determined to be
      dose level 3 (150 mg/m(2) for irinotecan and AUC = 5 for carboplatin). In
      contrast, the MTD was determined to be dose level 4 (200 mg/m(2) for irinotecan
      and AUC 5 for carboplatin) by modified-Fibonacci simulation. Conclusions. The
      population-based design of phase I trial allows optimization of dose intensity
      and derivation of a pMTD. The pMTD has been applied in phase II trial of
      irinotecan and carboplatin in patients with small-cell lung cancer.

PMID- 19404407
TI  - Type I interferons and interferon regulatory factors regulate TNF-related
      apoptosis-inducing ligand (TRAIL) in HIV-1-infected macrophages.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that
      participates in HIV-1 pathogenesis through the depletion of CD4+ T cells. TRAIL
      is expressed on the cell membrane of peripheral immune cells and can be cleaved
      into a soluble, secreted form. The regulation of TRAIL in macrophages during HIV
      1 infection is not completely understood. In this study, we investigated the
      mechanism(s) of TRAIL expression in HIV-1-infected macrophages, an important cell
      type in HIV-1 pathogenesis. A human monocyte-derived macrophage (MDM) culture
      system was infected with macrophage-tropic HIV-1(ADA), HIV-1(JR-FL), or HIV
      1(BAL) strains. TRAIL, predominantly the membrane-bound form, increased following
      HIV-1 infection. We found that HIV-1 infection also induced interferon regulatory
      factor (IRF)-1, IRF-7 gene expression and signal transducers and activators of
      transcription 1 (STAT1) activation. Small interfering RNA knockdown of IRF-1 or
      IRF-7, but not IRF-3, reduced STAT1 activation and TRAIL expression. Furthermore,
      the upregulation of IRF-1, IRF-7, TRAIL, and the activation of STAT1 by HIV-1
      infection was reduced by the treatment of type I interferon (IFN)-neutralizing
      antibodies. In addition, inhibition of STAT1 by fludarabine abolished IRF-1, IRF
      7, and TRAIL upregulation. We conclude that IRF-1, IRF-7, type I IFNs, and STAT1
      form a signaling feedback loop that is critical in regulating TRAIL expression in
      HIV-1-infected macrophages.

PMID- 19404409
TI  - Hemoperitoneum in a cirrhotic patient due to rupture of retroperitoneal varix.
AB  - The rupture of retroperitoneal varices is a rare and catastrophic complication of
      portal hypertension. We describe a case of this nature, the first in Brazilian
      medical literature, and also reviewing all previous 34 cases. We systematically
      analyzed all therapeutic approach and propose a management algorithm for
      diagnosis and treatment of this lethal condition. The majority of the patients
      presented with abdominal pain, distention and hypotension, and developed
      hemorrhagic shock. Rupture of retroperitoneal varices can be properly managed if
      an early diagnosis is made and surgery is performed promptly, which is the only
      effective treatment. Arteriography should be used when the suspicion is of
      rupture of hepatocellular carcinoma.

PMID- 19404410
TI  - Early, low-level auditory-somatosensory multisensory interactions impact reaction
      time speed.
AB  - Several lines of research have documented early-latency non-linear response
      interactions between audition and touch in humans and non-human primates. That
      these effects have been obtained under anesthesia, passive stimulation, as well
      as speeded reaction time tasks would suggest that some multisensory effects are
      not directly influencing behavioral outcome. We investigated whether the initial
      non-linear neural response interactions have a direct bearing on the speed of
      reaction times. Electrical neuroimaging analyses were applied to event-related
      potentials in response to auditory, somatosensory, or simultaneous auditory
      somatosensory multisensory stimulation that were in turn averaged according to
      trials leading to fast and slow reaction times (using a median split of
      individual subject data for each experimental condition). Responses to
      multisensory stimulus pairs were contrasted with each unisensory response as well
      as summed responses from the constituent unisensory conditions. Behavioral
      analyses indicated that neural response interactions were only implicated in the
      case of trials producing fast reaction times, as evidenced by facilitation in
      excess of probability summation. In agreement, supra-additive non-linear neural
      response interactions between multisensory and the sum of the constituent
      unisensory stimuli were evident over the 40-84 ms post-stimulus period only when
      reaction times were fast, whereas subsequent effects (86-128 ms) were observed
      independently of reaction time speed. Distributed source estimations further
      revealed that these earlier effects followed from supra-additive modulation of
      activity within posterior superior temporal cortices. These results indicate the
      behavioral relevance of early multisensory phenomena.

PMID- 19404412
TI  - What is the Most Sensitive Measure of Water Maze Probe Test Performance?
AB  - The water maze is commonly used to assay spatial cognition, or, more generally,
      learning and memory in experimental rodent models. In the water maze, mice or
      rats are trained to navigate to a platform located below the water's surface.
      Spatial learning is then typically assessed in a probe test, where the platform
      is removed from the pool and the mouse or rat is allowed to search for it.
      Performance in the probe test may then be evaluated using either occupancy-based
      (percent time in a virtual quadrant [Q] or zone [Z] centered on former platform
      location), error-based (mean proximity to former platform location [P]) or
      counting-based (platform crossings [X]) measures. While these measures differ in
      their popularity, whether they differ in their ability to detect group
      differences is not known. To address this question we compiled five separate
      databases, containing more than 1600 mouse probe tests. Random selection of
      individual trials from respective databases then allowed us to simulate
      experiments with varying sample and effect sizes. Using this Monte Carlo-based
      method, we found that the P measure consistently outperformed the Q, Z and X
      measures in its ability to detect group differences. This was the case regardless
      of sample or effect size, and using both parametric and non-parametric
      statistical analyses. The relative superiority of P over other commonly used
      measures suggests that it is the most appropriate measure to employ in both low-
      and high-throughput water maze screens.

PMID- 19404413
TI  - Reprogramming somatic cells to their embryonic state.
AB  - Embryonic stem (ES) cells have the capacity to form every type of cell in our
      adult bodies due to their pluripotency. The prospective use of ES cells in
      regenerative therapies for human diseases such as Parkinson's disease and
      diabetes has raised the interest in identifying the mechanisms that allow these
      cells to maintain pluripotent fate and differentiate along many lineages.
      However, ethical questions regarding the use of human eggs andor embryos for
      medical research have limited the ability of scientists to develop therapies with
      human ES cells. Three recent papers in Nature and Cell Stem Cell have revealed
      novel methods of reprogramming somatic cells into cells with the same pluripotent
      potential as ES cells via the expression of only four transcription factors.
      These scientific advances illuminate the mechanisms that drive pluripotent fate
      in embryonic cells. In addition, by giving scientists a model to study ES-like
      cells that are not derived from embryos, these newly identified models have the
      potential to progress therapies for regenerative medicine.

PMID- 19404414
TI  - The subtle benefits of being promiscuous: adaptive evolution potentiated by
      enzyme promiscuity.
AB  - In this commentary we discuss recent progress in our understanding of adaptive
      protein evolution. We begin with a general introduction to proteins and their
      evolution, quickly focusing on the question of how natural selection produces
      proteins with novel functions. We then summarize the theory of latent protein
      adaptation advanced by the joint articles by Amitai et al. (2007), HFSP J. 1, 67
      78 and Wroe et al. (2007) HFSP J. 1, 79-87, published in the first issue edition
      of the HFSP Journal. This theory provides a biophysical framework linking the
      effects of individual mutations on promiscuous protein function, neutral genetic
      drift, and gene duplication to the process of adaptive protein evolution.

PMID- 19404411
TI  - Extracting kinematic parameters for monkey bipedal walking from cortical neuronal
      ensemble activity.
AB  - The ability to walk may be critically impacted as the result of neurological
      injury or disease. While recent advances in brain-machine interfaces (BMIs) have
      demonstrated the feasibility of upper-limb neuroprostheses, BMIs have not been
      evaluated as a means to restore walking. Here, we demonstrate that chronic
      recordings from ensembles of cortical neurons can be used to predict the
      kinematics of bipedal walking in rhesus macaques - both offline and in real time.
      Linear decoders extracted 3D coordinates of leg joints and leg muscle
      electromyograms from the activity of hundreds of cortical neurons. As more
      complex patterns of walking were produced by varying the gait speed and
      direction, larger neuronal populations were needed to accurately extract walking
      patterns. Extraction was further improved using a switching decoder which
      designated a submodel for each walking paradigm. We propose that BMIs may one day
      allow severely paralyzed patients to walk again.

PMID- 19404415
TI  - Phenotypic evolution is restrained by complex developmental processes.
AB  - The paper, "Evolution and development of inflorescence architectures" by
      Przemyslaw Prusinkiewicz, Yvette Erasmus, Brendan Lane, Lawrence D. Harder and
      Enrico Coen [Science, 316, 1452-1456 (2007)], sets to accomplish a longstanding
      goal: to explain, for the first time, how and to what extent developmental
      constraints restrict phenotypic evolution. Prusinkiewicz and collaborators
      provide a relatively simple model that accounts for the variety of patterns of
      inflorescence architecture found among angiosperms, in which only a few of all
      possible types are observed.

PMID- 19404417
TI  - The New Robotics-towards human-centered machines.
AB  - Research in robotics has moved away from its primary focus on industrial
      applications. The New Robotics is a vision that has been developed in past years
      by our own university and many other national and international research
      institutions and addresses how increasingly more human-like robots can live among
      us and take over tasks where our current society has shortcomings. Elder care,
      physical therapy, child education, search and rescue, and general assistance in
      daily life situations are some of the examples that will benefit from the New
      Robotics in the near future. With these goals in mind, research for the New
      Robotics has to embrace a broad interdisciplinary approach, ranging from
      traditional mathematical issues of robotics to novel issues in psychology,
      neuroscience, and ethics. This paper outlines some of the important research
      problems that will need to be resolved to make the New Robotics a reality.

PMID- 19404416
TI  - Chemical genetics: reshaping biology through chemistry.
AB  - To understand biological processes, biologists typically study how perturbations
      of protein functions affect the phenotype. Protein activity in living cells can
      be influenced in many different ways: by manipulation of the genomic information,
      by injecting inhibitory antibodies, or, more recently, by the use of ribonucleic
      acid-medicated interference (RNAi). All these methods have proven to be extremely
      helpful, as they possess a high degree of specificity. However, they are less
      suitable for experiments requiring precise timing and fast reversibility of the
      perturbation. The advantage of small molecules is that they specifically interact
      with their target on a fast time scale and often in a reversible manner. In the
      last 15 years, this approach, termed "chemical genetics," has received a lot of
      attention. The term genetics pays tribute to the analogy between chemical
      genetics and the classic genetic approach, where manipulations at the gene level
      are used to draw conclusions about the function of the corresponding protein.
      Chemical genetics has only recently been used as a systematic approach in
      biology. The term was coined in the 1990's, when combinatorial chemistry was
      developed as a fast method to synthesize large compound libraries [Mitchison
      (1994) "Towards a pharmacological genetics," Chem. Biol. 1, 3-6; Schreiber (1998)
      "Chemical genetics resulting from a passion for synthetic organic chemistry,"
      Bioorg. Med. Chem. 6, 1127-1152].

PMID- 19404418
TI  - Characterizing multiple metal ion binding sites within a ribozyme by cadmium
      induced EPR silencing.
AB  - In ribozyme catalysis, metal ions are generally known to make structural andor
      mechanistic contributions. The catalytic activity of a previously described Diels
      Alderase ribozyme was found to depend on the concentration of divalent metal
      ions, and crystallographic data revealed multiple binding sites. Here, we
      elucidate the interactions of this ribozyme with divalent metal ions in solution
      using electron paramagnetic resonance (EPR) spectroscopy. Manganese ion
      titrations revealed five high-affinity Mn(2+) binding sites with an upper K(d) of
      0.6+/-0.2 muM. In order to characterize each binding site individually, EPR
      silent Cd(2+) ions were used to saturate the other binding sites. This cadmium
      induced EPR silencing showed that the Mn(2+) binding sites possess different
      affinities. In addition, these binding sites could be assigned to three different
      types, including innersphere, outersphere, and a Mn(2+) dimer. Based on
      simulations, the Mn(2+)-Mn(2+) distance within the dimer was found to be
      approximately 6 A, which is in good agreement with crystallographic data. The EPR
      spectroscopic characterization reveals no structural changes upon addition of a
      Diels-Alder product, supporting the concept of a preorganized catalytic pocket in
      the Diels-Alder ribozyme and the structural role of these ions.

PMID- 19404419
TI  - Characterization of the nucleation barriers for protein aggregation and amyloid
      formation.
AB  - Despite the complexity and the specificity of the amino acid code, a variety of
      peptides and proteins unrelated in sequence and function exhibit a common
      behavior and assemble into highly organized amyloid fibrils. The formation of
      such aggregates is often described by a nucleation and growth mechanism, in which
      the proteins involved also form intermediate oligomeric aggregates before they
      reorganize and grow into ordered fibrils with a characteristic cross-beta
      structure. It is extremely difficult to experimentally obtain an accurate
      description of the early stages of this phenomenon due to the transient nature
      and structural heterogeneity of the oligomeric precursors. We investigate here
      the phenomenon of ordered aggregation by using the recently introduced tube model
      of polypeptide chains in conjunction with the generic hypothesis of amyloid
      formation. Under conditions where oligomer formation is a rare event-the most
      common conditions for forming amyloid fibrils by experiment-we calculate directly
      the nucleation barriers associated with oligomer formation and conversion into
      cross-beta structure in order to reveal the nature of these species, determine
      the critical nuclei, and characterize their dependence on the hydrophobicity of
      the peptides and the thermodynamic parameters associated with aggregation and
      amyloid formation.

PMID- 19404420
TI  - Building a realistic neuronal model that simulates multi-joint arm and hand
      movements in 3D space.
AB  - The question as to how the brain controls voluntary movements of the arm and hand
      still remains largely unsolved despite much research focused on behavioral
      studies, neurophysiological investigations, and neuronal modeling in computer
      science. This is because behavioral studies are usually performed without
      detailed knowledge of the underlying neuronal networks, neurophysiological
      studies often lack an understanding of the function, and neuronal models are
      frequently focused on a particular control problem with restricted knowledge of
      the underlying neuronal networks involved. Therefore, it seems appropriate to
      start by trying to integrate knowledge of neuronal networks with known function
      and computer based neuronal models to seek more realistic models that can better
      control robots or artificial limbs and hands. We propose to combine knowledge of
      a behavioral model for reaching with the hand toward an object, which is based on
      detailed knowledge of the underlying neuronal network, and a neuronal model that
      includes several functional levels, from the planning level via intermediate
      levels to the final level of control of motoneurons and muscles.

PMID- 19404421
TI  - Molecular mechanics and DNA replication regulation.
AB  - Magnetic and optical tweezers are providing novel insights on the structure,
      energetics, and functional dynamics of biological macromolecules. The modulation
      of DNA topology has provided very appropriate opportunities to study with these
      technologies the energetic and mechanistic features of the action of DNA
      topoisomerases, the enzymes that maintain the physiological level of negative
      superhelicity in the genome. Modulation of the superhelical state of the DNA
      replication origins is essential for the initiation of DNA synthesis in
      prokaryotes and eukaryotes. The results obtained recently from independent
      studies of two different groups combine to give new insights on the topological
      aspects of this process. With magnetic tweezers it was shown that the inhibition
      of human topoisomerase I by camptothecin freezes the drug-enzyme-DNA complex and
      specifically forbids the relaxation of positive supercoils; a study of the in
      vivo role of topoisomerase I on the activation of a human origin showed that this
      process is forbidden when the enzyme is frozen on the origin DNA by camptothecin.
      The inhibition of the relaxation of positive supercoils, probably introduced by
      the proteins performing origin activation, is therefore lethal for this process.
      Thus, the use of advanced physical technologies provides insights on an essential
      biological process.

PMID- 19404422
TI  - Trapping the nematode on a micro chip for the future of science.
AB  - At the basis of neuroscience is the correlation between behavior and neural
      signals. This relationship is studied using a variety of techniques, including
      fluorescent intensity measurements of genetically encoded calcium indicators. The
      simple structure and conservation of some basic developmental pathways between
      vertebrates and Caenorhabditis elegans makes it an ideal model for studies
      employing this technique, but it has been difficult to apply neural stimuli in a
      controlled way to such a small organism. New microfabrication techniques allow
      the creation of "worm traps" via a combination of lithography and microfluidic
      regulation. These micro-scale devices have made possible the immobilization of
      nematodes in the absence of glue (which could affect the worms' neural activity),
      in addition to offering more control over the application and removal of stimuli
      than was possible in previous experimental setups. Chronis et al. link an
      increase in AVA (a type of motor neurons formed by bilaterally symmetric
      interneuron pairs) neural activity to the initiation of anterior-traveling body
      waves, and observed an increase in ASH (a type of sensory neurons responsible for
      a wide range of avoidance behaviors in response to chemical and physical
      stimulations) neural activity in response to stimulation by high osmotic strength
      solutions. The microfabrication developments described can be combined with
      recent advances in the biological sciences, in particular the developmental
      embryology, to yield solutions to important problems, such as the detection of
      low concentration substrates and the analysis of homeostasis and embryonic
      development.

PMID- 19404423
TI  - Fat(al) attraction: oxidized lipids act as "eat-me" signals.
AB  - Phagocytosis of apoptotic cell corpses is a conserved and well-regulated process
      and is required to maintain tissue homeostasis within an organism. Evidence
      suggests that apoptotic cell engulfment by macrophages is dependent upon the
      externalization of phosphatidylserine (PS) on the plasma membrane of the dying
      cell. Furthermore, oxidation of PS and other phospholipids may serve to
      facilitate cell corpse removal. However, our understanding of how these various
      lipid "eat-me" signals are recognized by macrophages has been limited. Using a
      combination of cellular and animal models, along with an array of biophysical
      methods, Hazen and his associates (Greenberg et al., J. Exp. Med., 2006, 203,
      2613-2625;Li et al., Biochemistry, 2007, 46, 5009-5017) have now identified the
      scavenger receptor CD36 as a putative receptor for oxidized PS on apoptotic
      cells; moreover, they have deduced the conformation of the oxidized lipid ligand
      that is recognized by this receptor, thus providing structural insight into how
      phagocytes recognize senescent or apoptotic cells.

PMID- 19404425
TI  - Uninformative memories will prevail: the storage of correlated representations
      and its consequences.
AB  - Autoassociative networks were proposed in the 80's as simplified models of memory
      function in the brain, using recurrent connectivity with Hebbian plasticity to
      store patterns of neural activity that can be later recalled. This type of
      computation has been suggested to take place in the CA3 region of the hippocampus
      and at several levels in the cortex. One of the weaknesses of these models is
      their apparent inability to store correlated patterns of activity. We show,
      however, that a small and biologically plausible modification in the "learning
      rule" (associating to each neuron a plasticity threshold that reflects its
      popularity) enables the network to handle correlations. We study the stability
      properties of the resulting memories (in terms of their resistance to the damage
      of neurons or synapses), finding a novel property of autoassociative networks:
      not all memories are equally robust, and the most informative are also the most
      sensitive to damage. We relate these results to category-specific effects in
      semantic memory patients, where concepts related to "non-living things" are
      usually more resistant to brain damage than those related to "living things," a
      phenomenon suspected to be rooted in the correlation between representations of
      concepts in the cortex.

PMID- 19404426
TI  - Understanding complex behaviors by analyzing optimized models: C. elegans
      gradient navigation.
AB  - We study how individual components of a complex behavior, so-called behavioral
      units, should be sequentially arranged when the overall goal is energy
      efficiency. We apply an optimization scheme to an existing probabilistic model of
      C. elegans chemical gradient navigation and find a family of solutions that share
      common properties. This family is used to analyze general principles of
      behavioral unit organization, which give rise to search strategies that match
      qualitatively with those observed in the animal. Specifically, the reorientation
      behavior emerging in energy efficient virtual worm searchers mimics the pirouette
      strategy observed in C. elegans, and the virtual worms dwell at the peak of the
      gradient. Our model predicts that pirouettes are in part associated with the
      inability to evaluate the gradient during a turn and that the animal does not act
      upon gradient information while reversing. Together, our results indicate that
      energy efficiency is an important factor in determining C. elegans gradient
      navigation. Our framework for the analysis of complex behaviors may, in the
      future, be used as part of an integrated approach to studying the neural basis of
      these behaviors.

PMID- 19404427
TI  - Acoustic physics of surface-attached biochemical species.
AB  - In this Commentary, we discuss the paper Quantitative Determination of Size and
      Shape of Surface-Bound DNA Using an Acoustic Wave Sensor [Tsortos et al.,
      Biophys. J. 94(7), 2706-2715 (2008)]. The paper under discussion presents a novel
      theory that uses the response of a Shear-Horizontal Surface Acoustic Wave device
      to characterize surface-attached double- and triple-strand DNA. The authors
      relate the length and curvature of the DNA strands to the interfacial viscosity
      using classical polymer theory. In this Commentary, we discuss their results in
      the broader context of acoustic wave detection of biochemical interactions and
      some of the factors involved when probing "soft" surfaces. Specifically, we
      present a review of interfacial coupling and slip, and discuss how these
      phenomena can affect biosensors employing acoustic wave detection techniques.

PMID- 19404424
TI  - Molecular tools for cell and systems biology.
AB  - The sequencing of the genomes of key organisms and the subsequent identification
      of genes merely leads us to the next real challenge in modern biology-revealing
      the precise functions of these genes. Further, detailed knowledge of how the
      products of these genes behave in space and time is required, including their
      interactions with other molecules. In order to tackle these considerable tasks, a
      large and continuously expanding toolbox is required to probe the functions of
      proteins on a cellular level. Here, the currently available tools are described
      and future developments are projected. There is no doubt that only the close
      interplay between the life science disciplines in addition to advances in
      engineering will be able to meet the challenge.

PMID- 19404428
TI  - Molecular motors: a traffic cop within?
AB  - Intracellular transport along microtubules is often bidirectional, employing
      multiple plus- and minus-end directed motors. How cells regulate such transport
      in time and space is a fundamental but unsolved question in cell biology. A
      recent paper presents a new modeling approach to predict how much of transport
      can be understood just from our knowledge of the motors involved. The model can
      generate strikingly complex patterns of motion, mimicking key aspects of cargo
      transport in vivo. Previous studies had inferred that plus-end motors on
      bidirectional cargoes are usually turned off when the minus-end motors are
      engaged (and vice versa). In the model, such motor coordination can arise from
      motors competing in a tug-of-war, without help from additional regulators. This
      new theoretical framework should stimulate much research that will help unravel
      whether regulation of intracellular transport is dominated by higher-order
      control mechanisms or is achieved simply by tuning basic properties of the motors
      themselves.

PMID- 19404429
TI  - Gene regulatory network inference using out of equilibrium statistical mechanics.
AB  - Spatiotemporal control of gene expression is fundamental to multicellular life.
      Despite prodigious efforts, the encoding of gene expression regulation in
      eukaryotes is not understood. Gene expression analyses nourish the hope to
      reverse engineer effector-target gene networks using inference techniques.
      Inference from noisy and circumstantial data relies on using robust models with
      few parameters for the underlying mechanisms. However, a systematic path to gene
      regulatory network reverse engineering from functional genomics data is still
      impeded by fundamental problems. Recently, Johannes Berg from the Theoretical
      Physics Institute of Cologne University has made two remarkable contributions
      that significantly advance the gene regulatory network inference problem. Berg,
      who uses gene expression data from yeast, has demonstrated a nonequilibrium
      regime for mRNA concentration dynamics and was able to map the gene regulatory
      process upon simple stochastic systems driven out of equilibrium. The impact of
      his demonstration is twofold, affecting both the understanding of the operational
      constraints under which transcription occurs and the capacity to extract relevant
      information from highly time-resolved expression data. Berg has used his
      observation to predict target genes of selected transcription factors, and
      thereby, in principle, demonstrated applicability of his out of equilibrium
      statistical mechanics approach to the gene network inference problem.

PMID- 19404430
TI  - Exploring the transport of plant metabolites using positron emitting
      radiotracers.
AB  - Short-lived positron-emitting radiotracer techniques provide time-dependent data
      that are critical for developing models of metabolite transport and resource
      distribution in plants and their microenvironments. Until recently these
      techniques were applied to measure radiotracer accumulation in coarse regions
      along transport pathways. The recent application of positron emission tomography
      (PET) techniques to plant research allows for detailed quantification of real
      time metabolite dynamics on previously unexplored spatial scales. PET provides
      dynamic information with millimeter-scale resolution on labeled carbon, nitrogen,
      and water transport over a small plant-size field of view. Because details at the
      millimeter scale may not be required for all regions of interest, hybrid
      detection systems that combine high-resolution imaging with other radiotracer
      counting technologies offer the versatility needed to pursue wide-ranging plant
      physiological and ecological research. In this perspective we describe a recently
      developed hybrid detection system at Duke University that provides researchers
      with the flexibility required to carry out measurements of the dynamic responses
      of whole plants to environmental change using short-lived radiotracers. Following
      a brief historical development of radiotracer applications to plant research, the
      role of radiotracers is presented in the context of various applications at the
      leaf to the whole-plant level that integrates cellular and subcellular signals
      andor controls.

PMID- 19404431
TI  - Collective behavior in animal groups: theoretical models and empirical studies.
AB  - Collective phenomena in animal groups have attracted much attention in the last
      years, becoming one of the hottest topics in ethology. There are various reasons
      for this. On the one hand, animal grouping provides a paradigmatic example of
      self-organization, where collective behavior emerges in absence of centralized
      control. The mechanism of group formation, where local rules for the individuals
      lead to a coherent global state, is very general and transcends the detailed
      nature of its components. In this respect, collective animal behavior is a
      subject of great interdisciplinary interest. On the other hand, there are several
      important issues related to the biological function of grouping and its
      evolutionary success. Research in this field boasts a number of theoretical
      models, but much less empirical results to compare with. For this reason, even if
      the general mechanisms through which self-organization is achieved are
      qualitatively well understood, a quantitative test of the models assumptions is
      still lacking. New analysis on large groups, which require sophisticated
      technological procedures, can provide the necessary empirical data.

PMID- 19404433
TI  - Toward integration of in vivo molecular computing devices: successes and
      challenges.
AB  - The computing power unleashed by biomolecule based massively parallel
      computational units has been the focus of many interdisciplinary studies that
      couple state of the art ideas from mathematical logic, theoretical computer
      science, bioengineering, and nanotechnology to fulfill some computational task.
      The output can influence, for instance, release of a drug at a specific target,
      gene expression, cell population, or be a purely mathematical entity. Analysis of
      the results of several studies has led to the emergence of a general set of rules
      concerning the implementation and optimization of in vivo computational units.
      Taking two recent studies on in vivo computing as examples, we discuss the impact
      of mathematical modeling and simulation in the field of synthetic biology and on
      in vivo computing. The impact of the emergence of gene regulatory networks and
      the potential of proteins acting as "circuit wires" on the problem of
      interconnecting molecular computing device subunits is also highlighted.

PMID- 19404432
TI  - Actomyosin purse strings: renewable resources that make morphogenesis robust and
      resilient.
AB  - Dorsal closure in Drosophila is a model system for cell sheet morphogenesis and
      wound healing. During closure two sheets of lateral epidermis move dorsally to
      close over the amnioserosa and form a continuous epidermis. Forces from the
      amnioserosa and actomyosin-rich, supracellular purse strings at the leading edges
      of these lateral epidermal sheets drive closure. Purse strings generate the
      largest force for closure and occur during development and wound healing
      throughout phylogeny. We use laser microsurgery to remove some or all of the
      purse strings from developing embryos. Free edges produced by surgery undergo
      characteristic responses as follows. Intact cells in the free edges, which
      previously had no purse string, recoil away from the incision and rapidly
      assemble new, secondary purse strings. Next, recoil slows, then pauses at a
      turning point. Following a brief delay, closure resumes and is powered to
      completion by the secondary purse strings. We confirm that the assembly of the
      secondary purse strings requires RhoA. We show that alpha-actinin alternates with
      nonmuscle myosin II along purse strings and requires nonmuscle myosin II for its
      localization. Together our data demonstrate that purse strings are renewable
      resources that contribute to the robust and resilient nature of closure.

PMID- 19404434
TI  - Making connections for life: an in vivo map of the yeast interactome.
AB  - Proteins are the true workhorses of any cell. To carry out specific tasks, they
      frequently bind other molecules in their surroundings. Due to their structural
      complexity and flexibility, the most diverse array of interactions is seen with
      other proteins. The different geometries and affinities available for such
      interactions typically bestow specific functions on proteins. Having available a
      map of protein-protein interactions is therefore of enormous importance for any
      researcher interested in gaining insight into biological systems at the level of
      cells and organisms. In a recent report, a novel approach has been employed that
      relies on the spontaneous folding of complementary enzyme fragments fused to two
      different proteins to test whether these interact in their actual cellular
      context [Tarassov et al., Science 320, 1465-1470 (2008)]. Genome-wide application
      of this protein-fragment complementation assay has resulted in the first map of
      the in vivo interactome of Saccharomyces cerevisiae. The current data show
      striking similarities but also significant differences to those obtained using
      other large-scale approaches for the same task. This warrants a general
      discussion of the current state of affairs of protein-protein interaction studies
      and foreseeable future trends, highlighting their significance for a variety of
      applications and their potential to revolutionize our understanding of the
      architecture and dynamics of biological systems.

PMID- 19404435
TI  - Pulsing cells: how fast is too fast?
AB  - Signal transduction pathways are complex coupled sets of biochemical reactions
      evolved to transmit and process information about the state of the immediate cell
      environment. Can we design experiments that would inform us about the properties
      and limitations of signal processing? Recent studies suggest that this indeed can
      be achieved by exciting a cell with carefully designed oscillatory stimuli.
      Although this analysis has its caveats, complex temporal stimulation of signal
      transduction networks can serve to rapidly advance our understanding of these
      information channels and ultimately create intelligent ways of controlling them.

PMID- 19404436
TI  - Similia similibus: pairing of homologous chromosomes driven by the
      physicochemical properties of DNA.
AB  - Genetic recombination in eukaryotes requires the pairing of homologous
      chromosomes to allow precise molecular exchanges between chromosome pairs at
      intertwined structures called Holliday junctions, the formation of which requires
      the action of the RecA protein. The mechanism behind the precise pairing of
      structures as long as chromosomes remains mysterious. In yeast, during the
      initial phases of meiosis, chromosomes are paired at approximately 65 kilobase
      intervals via paranemic interactions that do not involve strand breakage nor the
      intervention of analogs of the RecA protein. It has been proposed that these
      paranemic interactions could occur between G-rich chromosomal regions, but
      putting in register stretches of homologous sequences hundreds of kb long remains
      challenging. Recent developments on the theory of the physicochemical properties
      of DNA in aqueous solutions, in presence of di- or multivalent counterions, leads
      to the prediction that molecules with the same sequence tend to pair
      spontaneously by paranemic interactions depending on the electrostatic properties
      of DNA. Experimental support for this prediction has now been provided in vitro
      with naked DNA. This newly discovered property of DNA duplexes may thus provide a
      clue to solve the puzzle of the premeiotic pairing.

PMID- 19404437
TI  - Nanoscale hydrodynamics in the cell: balancing motorized transport with
      diffusion.
AB  - One of the central problems in the cell is how to transport molecules around the
      cell to desired locations. Since low Reynolds number conditions apply and
      diffusional times are large, without the aid of molecular motors to transport the
      fluid quickly cells could not survive, yet diffusion is still essential for the
      ultimate delivery of the goods. This paradox of low Reynolds numberlarge Peclet
      number has been solved by the algal weed Chara corallina in ingenious ways, as
      the recent paper by Goldstein, et al. [Proc. Natl. Acad. Sci. 105, 3663-3667
      (2008)] discusses at a deep but accessible way using modern hydrodynamic
      modeling.

PMID- 19404438
TI  - Light sheet-based fluorescence microscopy: more dimensions, more photons, and
      less photodamage.
AB  - Light-sheet-based fluorescence microscopy (LSFM) is a fluorescence technique that
      combines optical sectioning, the key capability of confocal and two-photon
      fluorescence microscopes with multiple-view imaging, which is used in optical
      tomography. In contrast to conventional wide-field and confocal fluorescence
      microscopes, a light sheet illuminates only the focal plane of the detection
      objective lens from the side. Excitation is, thus, restricted to the fluorophores
      in the volume near the focal plane. This provides optical sectioning and allows
      the use of regular cameras in the detection process. Compared to confocal
      fluorescence microscopy, LSFM reduces photo bleaching and photo toxicity by up to
      three orders of magnitude. In LSFM, the specimen is embedded in a transparent
      block of hydrogel and positioned relative to the stationary light sheet using
      precise motorized translation and rotation stages. This feature is used to image
      any plane in a specimen. Additionally, multiple views obtained along different
      angles can be combined into a single data set with an improved resolution. LSFMs
      are very well suited for imaging large live specimens over long periods of time.
      However, they also perform well with very small specimens such as single yeast
      cells. This perspective introduces the principles of LSFM, explains the
      challenges of specimen preparation, and introduces the basics of a microscopy
      that takes advantage of multiple views.

PMID- 19404439
TI  - Cell adhesion and response to synthetic nanopatterned environments by steering
      receptor clustering and spatial location.
AB  - During adhesion and spreading, cells form micrometer-sized structures comprising
      transmembrane and intracellular protein clusters, giving rise to the formation of
      what is known as focal adhesions. Over the past two decades these structures have
      been extensively studied to elucidate their organization, assembly, and molecular
      composition, as well as to determine their functional role. Synthetic materials
      decorated with biological molecules, such as adhesive peptides, are widely used
      to induce specific cellular responses dependent on cell adhesion. Here, we focus
      on how surface patterning of such bioactive materials and organization at the
      nanoscale level has proven to be a useful strategy for mimicking both physical
      and chemical cues present in the extracellular space controlling cell adhesion
      and fate. This strategy for designing synthetic cellular environments makes use
      of the observation that most cell signaling events are initiated through
      recruitment and clustering of transmembrane receptors by extracellular-presented
      signaling molecules. These systems allow for studying protein clustering in cells
      and characterizing the signaling response induced by, e.g., integrin activation.
      We review the findings about the regulation of cell adhesion and focal adhesion
      assembly by micro- and nanopatterns and discuss the possible use of substrate
      stiffness and patterning in mimicking both physical and chemical cues of the
      extracellular space.

PMID- 19404441
TI  - Measuring variability.
AB  - GENE EXPRESSION IS A NOISY STOCHASTIC PROCESS, SINCE IT INVOLVES AT ITS CORE
      INTERACTIONS BETWEEN SINGLE MOLECULES: a polymerase and a binding site. However,
      many biological processes directly dependent upon gene expression are reliable.
      Prominent among them is morphogenesis: how are body parts so consistently
      generated and proportioned? In the early embryo, gradients of certain proteins
      called morphogens affect the pattern of cell differentiation and embryonic
      development. The variability in morphogen patterns and its effect in the
      proportions of the embryo has been intriguing biologists for a long time, but the
      limitations, variability and limited reproducibility of immunostaining of fixed
      embryos does not allow dynamic measurements. New tools now allow precise
      measurement of the variability of morphogen patterning in living Drosophila
      embryos, making it possible to probe the underlying mechanisms of development.

PMID- 19404442
TI  - Passing the El Greco test.
AB  - In recent years, the increasing use of modelling to capture biological complexity
      has revealed two complementary approaches. One is to build ever more
      comprehensive models in the hope that they will lead to useful predictions. The
      other approach is to get to the essence of the underlying processes by
      simplifying and clarifying complex problems through various levels of
      abstraction. Unfortunately, these two approaches are sometimes confounded, as is
      highlighted by a recent commentary by Alvarez-Buylla et al. [HFSP Journal, 1(2),
      99-103 (2007)]. Their commentary raises several concerns about a paper we
      published on the development of inflorescences, the branching structures that
      bear flowers. Alvarez-Buylla et al. claim that the model we propose is too
      simplistic and propose an alternative "toy model," which they believe is more
      realistic and can account for the data just as effectively. However, they do not
      run simulations based on their model. We show here that, depending on how this
      toy model is interpreted, it either does not deliver what Alvarez-Buylla et al.
      claim, or is a special case of the model we proposed, or is so vague that its
      consequences are unclear. Our analysis demonstrates the importance of modelling
      in simplifying, clarifying and following through the consequences of particular
      hypotheses. Without this it is all too easy to construct elaborate models on
      shaky foundations.

PMID- 19404440
TI  - Mechanical factors activate beta-catenin-dependent oncogene expression in APC
      mouse colon.
AB  - beta-catenin acts as a critical regulator of gastrointestinal homeostasis through
      its control of the Wnt signaling pathway, and genetic or epigenetic lesions which
      activate Wnt signaling are the primary feature of colon cancer. beta-catenin is
      also a key element of mechanotranscription pathways, leading to upregulation of
      master developmental gene expression during Drosophila gastrulation, or
      regulating mammalian bone development and maintenance. Here we investigate the
      impact of mechanical stimulation on the initiation of colon cancer. Myc and
      Twist1, two oncogenes regulated through beta-catenin, are expressed in response
      to transient compression in APC deficient (APC(1638N+)) colon tissue explants,
      but not in wild-type colon explants. Mechanical stimulation of APC(1638N+) tissue
      leads to the phosphorylation of beta-catenin at tyrosine 654, the site of
      interaction with E-cadherin, as well as to increased nuclear localization of beta
      catenin. The mechanical activation of Myc and Twist1 expression in APC(1638N+)
      colon can be prevented by blocking beta-catenin phosphorylation using Src kinase
      inhibitors. Microenvironmental signals are known to cooperate with genetic
      lesions to promote the nuclear beta-catenin accumulation which drives colon
      cancer. Here we demonstrate that when APC is limiting, mechanical strain, such as
      that associated with intestinal transit or tumor growth, can be interpreted by
      cells of preneoplastic colon tissue as a signal to initiate a beta-catenin
      dependent transcriptional program characteristic of cancer.

PMID- 19404444
TI  - Trends in fluorescence imaging and related techniques to unravel biological
      information.
AB  - Optical microscopy is among the most powerful tools that the physical sciences
      have ever provided biology. It is indispensable for basic lab work, as well as
      for cutting edge research, as the visual monitoring of life processes still
      belongs to the most compelling evidences for a multitude of biomedical
      applications. Along with the rapid development of new probes and methods for the
      analysis of laser induced fluorescence, optical microscopy over past years
      experienced a vast increase of both new techniques and novel combinations of
      established methods to study biological processes with unprecedented spatial and
      temporal precision. On the one hand, major technical advances have significantly
      improved spatial resolution. On the other hand, life scientists are moving toward
      three- and even four-dimensional cell biology and biophysics involving time as a
      crucial coordinate to quantitatively understand living specimen. Monitoring the
      whole cell or tissue in real time, rather than producing snap-shot-like two
      dimensional projections, will enable more physiological and, thus, more
      clinically relevant experiments, whereas an increase in temporal resolution
      facilitates monitoring fast nonperiodic processes as well as the quantitative
      analysis of characteristic dynamics.

PMID- 19404443
TI  - The origin of modern terrestrial life.
AB  - The study of the origin of life covers many areas of expertise and requires the
      input of various scientific communities. In recent years, this research field has
      often been viewed as part of a broader agenda under the name of "exobiology" or
      "astrobiology." In this review, we have somewhat narrowed this agenda, focusing
      on the origin of modern terrestrial life. The adjective "modern" here means that
      we did not speculate on different forms of life that could have possibly appeared
      on our planet, but instead focus on the existing forms (cells and viruses). We
      try to briefly present the state of the art about alternative hypotheses
      discussing not only the origin of life per se, but also how life evolved to
      produce the modern biosphere through a succession of steps that we would like to
      characterize as much as possible.

PMID- 19404445
TI  - Direct mechanical measurement of geodesic structures in rat mesenchymal stem
      cells.
AB  - During numerous biological processes, cell adhesion, cell migration and cell
      spreading are vital. These basic biological functions are regulated by the
      interaction of cells with their extracellular environment. To examine the
      morphology and mechanical changes occurring in mesenchymal stem cells cultured on
      a mechanically rigid substrate, atomic force microscopy and fluorescence
      microscopy were employed. Investigations of the cells revealed both linear and
      geodesic F-actin configurations. No particular cell characteristics or intra
      cellular location were implicated in the appearance of the geodesic structures.
      However, the length of time the cells were cultured on the substrate correlated
      with the percentage appearance of the geodesic structures. Calculating energy
      dissipation from cell images acquired by dynamic mode atomic force microscopy, it
      was observed that the vertices of the geodesic structures had significantly
      higher energy dissipation compared to the linear F-actin and the glass. This
      supports work by Lazarides [J. Cell Biol. 68, 202-219 (1976)], who postulated
      that the vertices of these geodesic structures should have a greater flexibility.
      Our results also support predictions based on the microfilament tensegrity model.
      By understanding the basic principles of cell ultrastructure and cell mechanics
      in relation to different extracellular environments, a better understanding of
      physiological and pathological process will be elicited.

PMID- 19404448
TI  - Quantitative analysis of fluorescence lifetime imaging made easy.
AB  - Fluorescence lifetime imaging is a valuable and versatile tool for the
      investigation of the molecular environment of fluorophores in living cells. It is
      ideally suited-and is therefore increasingly used-for the quantification of the
      occurrence of Forster Resonance Energy Transfer, a powerful microscopy method for
      the detection of subnanometer conformational changes, protein-protein
      interactions, and protein biochemical status. However, careful quantitative
      analysis is required for the correct and meaningful interpretation of
      fluorescence lifetime data. This can be a daunting task to the nonexpert user,
      and is the source for many avoidable errors and unsound interpretations. Digman
      and colleagues (Digman et al., 2007, Biophys. J. 94, L14-6) present an analysis
      technique that avoids data fitting in favor of a simple graphical polar data
      representation. In this "phasor" space, the physics of lifetime imaging becomes
      more intuitive and accessible also to the inexperienced user. The cumulated
      information from image pixels, even over different cells, describes patterns and
      trajectories that can be visually interpreted in physically meaningful ways. Its
      usefulness is demonstrated in the study of the dimerization of the uPAR receptor
      (Caiolfa et al., 2007, J. Cell Biol. 179, 1067-1082).

PMID- 19404446
TI  - How molecular motors shape the flagellar beat.
AB  - Cilia and eukaryotic flagella are slender cellular appendages whose regular
      beating propels cells and microorganisms through aqueous media. The beat is an
      oscillating pattern of propagating bends generated by dynein motor proteins. A
      key open question is how the activity of the motors is coordinated in space and
      time. To elucidate the nature of this coordination we inferred the mechanical
      properties of the motors by analyzing the shape of beating sperm: Steadily
      beating bull sperm were imaged and their shapes were measured with high precision
      using a Fourier averaging technique. Comparing our experimental data with wave
      forms calculated for different scenarios of motor coordination we found that only
      the scenario of interdoublet sliding regulating motor activity gives rise to
      satisfactory fits. We propose that the microscopic origin of such "sliding
      control" is the load dependent detachment rate of motors. Agreement between
      observed and calculated wave forms was obtained only if significant sliding
      between microtubules occurred at the base. This suggests a novel mechanism by
      which changes in basal compliance could reverse the direction of beat
      propagation. We conclude that the flagellar beat patterns are determined by an
      interplay of the basal properties of the axoneme and the mechanical feedback of
      dynein motors.

PMID- 19404447
TI  - Insight or illusion? Seeing inside the cell with mesoscopic simulations.
AB  - The expulsion of material from a cell by fusion of vesicles at the plasma
      membrane, and the entry of a virus by membrane invagination are complex membrane
      associated processes whose control is crucial to cell survival. Our ability to
      visualize the dynamics of such processes experimentally is limited by spatial
      resolution and the speed of molecular rearrangements. The increase in computing
      power of the last few decades enables the construction of computational tools for
      observing cellular processes in silico. As experiments yield increasing amounts
      of data on the protein and lipid constituents of the cell, computer simulations
      parametrized using this data are beginning to allow models of cellular processes
      to be interrogated in ways unavailable in the laboratory. Mesoscopic simulations
      retain only those molecular features that are believed to be relevant to the
      processes of interest. This allows the dynamics of spatially heterogeneous
      membranes and the crowded cytoplasmic environment to be followed at a modest
      computational cost. The price for such power is that the atomic detail of the
      constituents is much lower than in atomistic Molecular Dynamics simulations. We
      argue that this price is worth paying because mesoscopic simulations can generate
      new insight into the complex, dynamic life of a cell.

PMID- 19404450
TI  - Compositionality, stochasticity, and cooperativity in dynamic models of gene
      regulation.
AB  - We present an approach for constructing dynamic models for the simulation of gene
      regulatory networks from simple computational elements. Each element is called a
      "gene gate" and defines an inputoutput relationship corresponding to the binding
      and production of transcription factors. The proposed reaction kinetics of the
      gene gates can be mapped onto stochastic processes and the standard ordinary
      differential equation (ODE) description. While the ODE approach requires fixing
      the system's topology before its correct implementation, expressing them in
      stochastic pi-calculus leads to a fully compositional scheme: network elements
      become autonomous and only the inputoutput relationships fix their wiring. The
      modularity of our approach allows to pass easily from a basic first-level
      description to refined models which capture more details of the biological
      system. As an illustrative application we present the stochastic repressilator,
      an artificial cellular clock, which oscillates readily without any cooperative
      effects.

PMID- 19404449
TI  - The network and the synapse: 100 years after Cajal.
AB  - A century ago, Ramon y Cajal proposed that the brain consisted of huge numbers of
      neurons that communicated with each other through junctions called synapses.
      Today we routinely monitor single neuron and single synapse responses, and we
      have elaborate maps of connections between different regions of the brain. What
      we lack is a way to bridge these two scales of representing neuronal circuits.
      The challenges in doing so are formidable: even a small mammalian neuronal
      circuit has many thousands of neurons and millions of synapses. Can we keep track
      of individual cells and synapses in this crowd? Here we examine how two recent
      techniques may complement each other to do so. The recent "Brainbow" method is a
      way to color-code cells and their projections, so we can see which cells come
      near each other, but cannot be sure they connect. Functional circuit mapping
      tells us about connections between cells, but we cannot identify more than a
      handful at a time. Together these methods may fill in each other's blanks and
      give us brain wiring diagrams that combine scale and precision.

PMID- 19404452
TI  - Quantitative differences in tissue surface tension influence zebrafish germ layer
      positioning.
AB  - This study provides direct functional evidence that differential adhesion,
      measurable as quantitative differences in tissue surface tension, influences
      spatial positioning between zebrafish germ layer tissues. We show that embryonic
      ectodermal and mesendodermal tissues generated by mRNA-overexpression behave on
      long-time scales like immiscible fluids. When mixed in hanging drop culture,
      their cells segregate into discrete phases with ectoderm adopting an internal
      position relative to the mesendoderm. The position adopted directly correlates
      with differences in tissue surface tension. We also show that germ layer tissues
      from untreated embryos, when extirpated and placed in culture, adopt a
      configuration similar to those of their mRNA-overexpressing counterparts. Down
      regulating E-cadherin expression in the ectoderm leads to reduced surface tension
      and results in phase reversal with E-cadherin-depleted ectoderm cells now
      adopting an external position relative to the mesendoderm. These results show
      that in vitro cell sorting of zebrafish mesendoderm and ectoderm tissues is
      specified by tissue interfacial tensions. We perform a mathematical analysis
      indicating that tissue interfacial tension between actively motile cells
      contributes to the spatial organization and dynamics of these zebrafish germ
      layers in vivo.

PMID- 19404453
TI  - Changing disciplinary borders into frontiers of progress.

PMID- 19404454
TI  - Human frontier science: the program, the organization, and the journal.

PMID- 19404451
TI  - Role of bacterial peptidase F inferred by statistical analysis and further
      experimental validation.
AB  - Despite the quantity of high-throughput data available nowadays, the precise role
      of many proteins has not been elucidated. Available methods for classifying
      proteins and reconstructing metabolic networks are efficient for finding global
      categories, but do not answer the biologist's specific and targeted questions.
      Following Yamanishi et al. [Yamanishi, Y, Vert, JP, Nakaya, A, and Kaneisha, M
      (2003). "Extraction of correlated clusters from multiple genomic data by
      generalized kernel canonical correlation analysis." Bioinformatics 19, Suppl. 1,
      i323-i330] we used a kernel canonical correlation analysis (KCCA) to predict the
      role of the bacterial peptidase PepF. We integrated five existing data types:
      protein metabolic networks, microarray data, phylogenetic profiles, distances
      between proteins and incomplete two-dimensional-gel data (for which we propose a
      completion strategy), available for Lactococcus lactis to determine relationships
      between proteins. The predicted relationships were then used to guide our
      laboratory work which proved most of the predictions correct. PepF had previously
      been characterized as a zinc dependent endopeptidase [Nardi, M, Renault, P, and
      Monnet, V (1997). "Duplication of the pepF gene and shuffling of DNA fragments on
      the lactose plasmid of Lactococcus lactis." J. Bacteriol. 179, 4164-4171; Monnet,
      V, Nardi, M, Chopin, MC, and Gripon, JC (1994). "Biochemical and genetic
      characterization of PepF on oligoendopeptidase from Lactococcus lactis." J. Bio.
      Chem. 269, 32070-32076]. Analyzing a PepF mutant, we confirmed its participation
      in protein secretion through a strong relationship between the signal peptidase I
      and PepF predicted by the KCCA. The global nature of our approach made it
      possible to discover pleiotropic roles of the protein which had remained unknown
      using classical approaches.

PMID- 19404455
TI  - Probing synaptic signaling with quantum dots.
AB  - Synapses are the principal substrates of neuronal communication in the brain.
      Neuroscientists are trying to understand how the remodeling of synapses at the
      molecular level leads to changes in learning and memory. The lateral movement of
      neurotransmitter receptors is emerging as an important mechanism in the control
      of synaptic transmission. However, our understanding of the spatial dynamics of
      membrane receptors at synapses has been limited largely because of a lack of
      appropriate tools to resolve single receptors in living cells. Fluorescent
      quantum dots represent promising probes to monitor individual synaptic receptors
      in living neural circuits. Bats and colleagues (Bats, Groc, and Choquet, Neuron
      53, 719, 2007) used quantum dots to track the ins and outs of glutamate receptors
      at synapses, showing that the receptors bring company as they diffuse in the
      synapse to become trapped via their partner's local connections. Their study
      sheds new light on the mechanisms used by synapses to change their efficacy,
      which may impact on our understanding of the cellular and molecular basis of
      learning and memory.

PMID- 19404456
TI  - Bundling, sliding, and pulling microtubules in cells and in silico.
AB  - Microtubules and other proteins self-organize into complex dynamic structures
      such as the mitotic spindle, which separates the chromosomes during cell
      division. Much is known about the individual molecular players involved in
      assembly and positioning of the mitotic spindle, but how they act together to
      generate the often unexpected behavior of the whole microtubule system is not
      understood. Two recent papers use a combination of experimental (imaging) and
      theoretical (computer simulation) methods to explore the formation of bipolar
      linear microtubule arrays in fission yeast and the oscillatory movement of the
      mitotic spindle in the nematode worm. In the simulation approach, the rules for
      the interactions of the components (microtubules and microtubule-associated
      proteins) are specified and the evolution of the system is followed, with the aim
      of identifying the minimal set of components that can mimic the real system. The
      work on fission yeast concludes that bipolar microtubule structures can arise
      from self-organization of microtubules through nucleators, bundlers, and sliders,
      without a requirement for a special microtubule-organizing center. The work on
      the worm embryo suggests that both the positive feedback that drives oscillations
      and the centering force that limits their amplitude may arise from microtubule
      pulling forces. The systems approach exemplified by these papers should stimulate
      new experiments aimed at discovering the principles of cellular organization.

PMID- 19404457
TI  - How single molecule detection measures the dynamic actions of life.
AB  - Biomolecules dynamically work in cells in which a variety of molecules assemble
      and interact in unique manner. The molecular mechanisms underlying several
      biological processes have been elucidated from the results obtained from the
      descriptions of cell function, from the snapshots of the structures of
      biomolecules involved in these processes, and from the biochemical properties of
      these reactions in vitro. Recently developed single molecule measurements have
      revealed the dynamic properties of the biomolecules that have been hidden in the
      data that have been averaged over large numbers of molecules in both ensemble
      measurement and in cells. Single molecule imaging and manipulation of single
      molecules have allowed the visualization of the dynamic operations of molecular
      motors, enzymatic reactions, structural dynamics of biomolecules, and cell
      signaling processes. The results have shown that the single molecule techniques
      are powerful tools to monitor the dynamic actions of biomolecules and their
      assemblies. This approach has been applied to a variety of fields within the life
      sciences. As new information emerges about the dynamic actions of biomolecules
      using methods of single molecule detection new views on how biological processes
      work will be revealed.

PMID- 19404458
TI  - Reinforcement learning: Computational theory and biological mechanisms.
AB  - Reinforcement learning is a computational framework for an active agent to learn
      behaviors on the basis of a scalar reward signal. The agent can be an animal, a
      human, or an artificial system such as a robot or a computer program. The reward
      can be food, water, money, or whatever measure of the performance of the agent.
      The theory of reinforcement learning, which was developed in an artificial
      intelligence community with intuitions from animal learning theory, is now giving
      a coherent account on the function of the basal ganglia. It now serves as the
      "common language" in which biologists, engineers, and social scientists can
      exchange their problems and findings. This article reviews the basic theoretical
      framework of reinforcement learning and discusses its recent and future
      contributions toward the understanding of animal behaviors and human decision
      making.

PMID- 19404459
TI  - Magnetoreception in birds: different physical processes for two types of
      directional responses.
AB  - Migratory orientation in birds involves an inclination compass based on radical
      pair processes. Under certain light regimes, however, "fixed-direction" responses
      are observed that do not undergo the seasonal change between spring and autumn
      typical for migratory orientation. To identify the underlying transduction
      mechanisms, we analyzed a fixed-direction response under a combination of 502 nm
      turquoise and 590 nm yellow light, with migratory orientation under 565 nm green
      light serving as the control. High-frequency fields, diagnostic for a radical
      pair mechanism, disrupted migratory orientation without affecting fixed-direction
      responses. Local anaesthesia of the upper beak where magnetite is found in birds,
      in contrast, disrupted the fixed-direction response without affecting migratory
      orientation. The two types of responses are thus based on different physical
      principles, with the compass response based on a radical pair mechanism and the
      fixed-direction responses probably originating in magnetite-based receptors in
      the upper beak. Directional input from these receptors seems to affect the
      behavior only when the regular inclination compass does not work properly.
      Evolutionary considerations suggest that magnetite-based receptors may represent
      an ancient mechanism that, in birds, has been replaced by the modern inclination
      compass based on radical-pair processes now used for directional orientation.

PMID- 19404460
TI  - A propagating ERKII switch forms zones of elevated dendritic activation
      correlated with plasticity.
AB  - Strong inputs to neurons trigger complex biochemical events leading to synaptic
      plasticity. These biochemical events occur at many spatial scales, ranging from
      submicron dendritic spines to signals that propagate hundreds of microns from
      dendrites to the nucleus. ERKII is an important signaling molecule that is
      involved in many aspects of plasticity, including local excitability,
      communication with the nucleus, and control of local protein synthesis. We
      observed that ERKII activation spreads long distances in apical dendrites of
      stimulated hippocampal CA1 pyramidal neurons. We combined experiments and models
      to show that this >100 mum spread was too large to be explained by biochemical
      reaction-diffusion effects. We show that two modes of calcium entry along the
      dendrite contribute to the extensive activation of ERKII. We predict the
      occurrence of feedback between biophysical events resulting in calcium entry, and
      biochemical events resulting in ERKII activation. This feedback causes a switch
      like propagation of ERKII activation, coupled with enhanced electrical
      excitability, along the apical dendrite. We propose that this propagating switch
      forms zones on dendrites in which plasticity is facilitated.

PMID- 19404461
TI  - Latent evolutionary potentials under the neutral mutational drift of an enzyme.
AB  - Biological systems exhibit mutational robustness, or neutrality, whereby the
      impact of mutations is minimized. Does neutrality hamper their ability to adapt
      in the face of changing environments? We monitored changes in genotype and
      phenotype that occur within a neutral mutational network of an enzyme,
      experimentally and computationally (see accompanying article). Using the enzyme
      PON1 as a model, we performed random mutagenesis and purifying selection to purge
      deleterious mutations. We characterized approximately 300 variants that are
      apparently neutral, or close to neutral, with respect to PON1's levels of
      expression and native lactonase activity. Their activities with promiscuous
      substrates and ligands indicated significant changes in adaptive potentials.
      Almost half of the variants exhibited changes in promiscuous activities,
      specificities, or inhibition, and several of these were found to be one or two
      mutations, closer to potentially new phenotypes: aryl esterase, thiolactonase,
      phosphotriesterase, or drug resistance. This empirical measure of phenotypic
      changes under neutrality supports the notion that sequence changes that are
      neutral, i.e., non-adaptive, in a current context can facilitate adaptation under
      changing circumstances, by both expanding the activity range of existing enzymes
      and thus providing an immediate advantage, and by reducing the number of
      mutations required for divergence of new functions.

PMID- 19404463
TI  - The HFSP Journal one year on: moving forward with a new feature.

PMID- 19404462
TI  - A structural model of latent evolutionary potentials underlying neutral networks
      in proteins.
AB  - A central question in molecular evolution concerns the nature of phenotypic
      transitions, in particular, if neutral mutations hamper or somehow facilitate
      adaptability of proteins to new requirements. Proteins have been found to
      fluctuate between different structures, with frequencies of structures being
      proportional to their stability. Therefore, functional promiscuity may correspond
      to different structures with energies close to the ground state which then
      represent multiple selectable traits. We here postulate that these near-ground
      state structures facilitate smooth transitions between phenotypes. Using a
      biophysical heteropolymer model with exhaustive mappings of sequences onto
      structures, we demonstrate that this is indeed possible because of a smooth
      gradient of stability along which any structural phenotype can be optimized and
      also because of mutational proximity of similar phenotypes in genotype space. Our
      model provides a biophysical rationalization of the intriguing, and otherwise
      puzzling experimental observation that adaptation to new requirements, e.g.,
      latent function of a promiscuous enzyme, can proceed while the "old,"
      phenotypically dominant function is maintained along a series of seemingly
      neutral mutations (see accompanying article). Thus pleiotropy may facilitate
      adaptation of latent traits before gene duplications and increase the effective
      adaptability of proteins.

PMID- 19404464
TI  - Tying new knots in synthetic biology.
AB  - Recent years have seen the emergence of synthetic biology, which encompasses the
      engineering of living organisms as well as the implementation of biological
      behavior in non-living substrates. Many of these engineered systems have
      harnessed the diverse toolkit of proteins, genes, and cellular processes that
      nature offers. While these efforts have been fruitful, they have also illustrated
      the difficulty associated with programming highly complex functions by tapping
      into cellular processes. Another set of efforts has focused on building circuits,
      performing computation, and constructing nanoscale machines using nucleic acids.
      Zhang et al., 2007, Science 318, 1121-1125 and Yin et al., 2008, Nature 451, 318
      322 recently demonstrated flexible approaches for the modular construction of
      such biochemical devices exclusively using DNA. These approaches have exciting
      implications both for engineering living cells and for mimicking life-like
      behavior at the nanoscale.

PMID- 19404465
TI  - Optical microscopy beyond the diffraction limit.
AB  - Over the past century the resolution of far-field optical microscopes, which rely
      on propagating optical modes, was widely believed to be limited because of
      diffraction to a value on the order of a half-wavelength lambda2 of the light
      used. Although immersion microscopes had slightly improved resolution on the
      order of lambda2n, the increased resolution was limited by the small range of
      refractive indices, n, of available transparent materials. We are experiencing
      quick demolition of the diffraction limit in optical microscopy. Over the past
      few years numerous nonlinear optical microscopy techniques based on
      photoswitching and saturation of fluorescence demonstrated far-field resolution
      of 20 to 30 nm. The latest exciting example of these techniques has been
      demonstrated by Huang et al. [Science 319, 810-813 (2008)]. Moreover, recent
      progress in metamaterials indicates that artificial optical media can be created,
      which do not exhibit the diffraction limit. Resolution of linear "immersion"
      microscopes based on such metamaterials appears limited only by losses, which can
      be compensated by gain media. Thus, optical microscopy is quickly moving towards
      the 10 nm resolution scale, which should bring about numerous revolutionary
      advances in biomedical imaging.

PMID- 19404466
TI  - Fixing the location and dimensions of functional neocortical columns.
AB  - The quest to understand the way in which neurons interconnect to form circuits
      that function as a unit began when Ramon y Cajal concluded that axo-dendritic
      apposition were too conspicuous to be incidental and proposed that two neurons
      must be communicating through these points of contact (see Shepherd and Erulkar,
      1997, Trends Neurosci., 20, 385-392). Lorente de No was probably the first to
      predict that a defined group of vertically displaced neurons in the neocortex
      could form functional units (Lorente de No, 1938, Physiology of the Nervous
      System, 20, OUP: 291-330) for which Mountcastle found experimental evidence (see
      Mountcastle, 1997, Brain, 120, 701-722) and which was ultimately demonstrated by
      Hubel and Wiesel in their elegant discovery of the orientation selective columns
      (Hubel and Wiesel, 1959, J. Physiol., 148, 574-591). Until today, however, it is
      still not clear what shapes functional columns. Anatomical units, as in the
      barrel cortex, would make it easier to explain, but the neocortex is largely a
      continuous slab of closely packed neurons from which multiple modules emerge that
      can overlap partially or even completely on the same anatomical space. Are the
      columns in fixed anatomical locations or are they dynamically assigned and what
      anatomical and physiological properties are operating to shape their dimensions?
      A recent study explores how the geometry of single neurons places structural
      constraints on the dimensions of columns in the visual cortex (Stepanyants et
      al., 2008, Cereb Cortex, 18, 13-24).

PMID- 19404467
TI  - Brain controlled robots.
AB  - In January 2008, Duke University and the Japan Science and Technology Agency
      (JST) publicized their successful control of a brain-machine interface for a
      humanoid robot by a monkey brain across the Pacific Ocean. The activities of a
      few hundred neurons were recorded from a monkey's motor cortex in Miguel
      Nicolelis's lab at Duke University, and the kinematic features of monkey
      locomotion on a treadmill were decoded from neural firing rates in real time. The
      decoded information was sent to a humanoid robot, CB-i, in ATR Computational
      Neuroscience Laboratories located in Kyoto, Japan. This robot was developed by
      the JST International Collaborative Research Project (ICORP) as the
      "Computational Brain Project." CB-i's locomotion-like movement was video-recorded
      and projected on a screen in front of the monkey. Although the bidirectional
      communication used a conventional Internet connection, its delay was suppressed
      below one over several seconds, partly due to a video-streaming technique, and
      this encouraged the monkey's voluntary locomotion and influenced its brain
      activity. This commentary introduces the background and future directions of the
      brain-controlled robot.

PMID- 19404469
TI  - Transistor analogs of emergent iono-neuronal dynamics.
AB  - Neuromorphic analog metal-oxide-silicon (MOS) transistor circuits promise
      compact, low-power, and high-speed emulations of iono-neuronal dynamics orders-of
      magnitude faster than digital simulation. However, their inherently limited input
      voltage dynamic range vs power consumption and silicon die area tradeoffs makes
      them highly sensitive to transistor mismatch due to fabrication inaccuracy,
      device noise, and other nonidealities. This limitation precludes robust analog
      very-large-scale-integration (aVLSI) circuits implementation of emergent iono
      neuronal dynamics computations beyond simple spiking with limited ion channel
      dynamics. Here we present versatile neuromorphic analog building-block circuits
      that afford near-maximum voltage dynamic range operating within the low-power MOS
      transistor weak-inversion regime which is ideal for aVLSI implementation or
      implantable biomimetic device applications. The fabricated microchip allowed
      robust realization of dynamic iono-neuronal computations such as coincidence
      detection of presynaptic spikes or pre- and postsynaptic activities. As a
      critical performance benchmark, the high-speed and highly interactive iono
      neuronal simulation capability on-chip enabled our prompt discovery of a minimal
      model of chaotic pacemaker bursting, an emergent iono-neuronal behavior of
      fundamental biological significance which has hitherto defied experimental
      testing or computational exploration via conventional digital or analog
      simulations. These compact and power-efficient transistor analogs of emergent
      iono-neuronal dynamics open new avenues for next-generation neuromorphic,
      neuroprosthetic, and brain-machine interface applications.

PMID- 19404468
TI  - Fast fluorescence microscopy for imaging the dynamics of embryonic development.
AB  - Live imaging has gained a pivotal role in developmental biology since it
      increasingly allows real-time observation of cell behavior in intact organisms.
      Microscopes that can capture the dynamics of ever-faster biological events,
      fluorescent markers optimal for in vivo imaging, and, finally, adapted
      reconstruction and analysis programs to complete data flow all contribute to this
      success. Focusing on temporal resolution, we discuss how fast imaging can be
      achieved with minimal prejudice to spatial resolution, photon count, or to
      reliably and automatically analyze images. In particular, we show how integrated
      approaches to imaging that combine bright fluorescent probes, fast microscopes,
      and custom post-processing techniques can address the kinetics of biological
      systems at multiple scales. Finally, we discuss remaining challenges and
      opportunities for further advances in this field.

PMID- 19404470
TI  - Kinetic proofreading of gene activation by chromatin remodeling.
AB  - Gene activation in eukaryotes involves the concerted action of histone tail
      modifiers, chromatin remodelers, and transcription factors, whose precise
      coordination is currently unknown. We demonstrate that the experimentally
      observed interactions of the molecules are in accord with a kinetic proofreading
      scheme. Our finding could provide a basis for the development of quantitative
      models for gene regulation in eukaryotes based on the combinatorical interactions
      of chromatin modifiers.

PMID- 19404471
TI  - Shining a light on post-translational modification.
AB  - Post-translational modification, such as phosphorylation or glycosylation,
      provides a mechanism for increasing the diversity of protein structures in the
      cell and regulating biological activity. In addition, such modifications may
      result in the localization of proteins to specific cellular organelles, with
      incorrect targeting being associated with a number of diseases. The simplest
      strategy to identify the functional importance of post-translational
      modifications is to use mutagenesis methods to replace the residue that is post
      translationally modified by one that cannot undergo the relevant chemical
      transformation. Merely causing "loss of function" does not, however, address
      questions concerning how cellular function depends on the timing of post
      translational changes andor the movement of modified proteins between organelles.
      The recent demonstration that genetically encoded "photocaged" proteins can be
      employed to resolve such issues therefore represents an exciting advance in this
      research area, and is an elegant illustration of the power of combining the power
      of chemical synthesis and methods for manipulating the biological machinery of
      protein synthesis.

PMID- 19404472
TI  - Energy landscape along an enzymatic reaction trajectory: hinges or cracks?
AB  - Are the most dynamically flexible regions around the equilibrium structure of an
      enzyme the same regions involved in the transition state for rate limiting
      processes involved in the enzymatic reaction? Kern and-coworkers (Wolf-Watzet
      al., 2004; Henzler-Wildman et al., 2007a, 2007b) have shown that insights about
      functionally relevant motions that determine the overall enzyme turnover rate can
      be obtained by investigating conformational dynamics around the equilibrium basin
      of the enzyme adenylate kinase. An allosteric change in protein structure turns
      out to be the controlling process. In this commentary we compare results of this
      study with earlier predictions of the route by which the enzyme undergoes its
      conformational change. These predictions are based on the idea that the energy
      surface for the protein is determined by the end structures of the conformational
      change. A key issue is whether the protein moves by specific hinges or whether it
      "cracks" and accesses partially unfolded states during its structural change.

PMID- 19404473
TI  - Get round and stiff for mitosis.
AB  - Cell rounding is a common feature of cell division. The spherical shape that
      cells adopt during mitosis is apparently neither a simple detachment nor a global
      softening or stiffening that allows cells to adopt what seems to be a mechanical
      equilibrium. It is a highly complex mechanical transformation by which membrane
      folding and peripheral signals focusing can match spindle size in order to ensure
      a proper cell division. Recent new insight into the mechanism involved will
      prompt the scientific community to focus on the regulation of the physical links
      that exist between the lipid bilayer membrane and the underlying actin
      cytoskeleton since it now appears that these will strongly influence some crucial
      cellular events such as the spatial organization of cell division.

PMID- 19404474
TI  - "Developmental mechanics": cellular patterns controlled by adhesion, cortical
      tension and cell division.
AB  - How embryos are shaped during development has inspired the work of many,
      embryologists, geneticists, but also mathematicians such as Turing, and
      physicists. Despite the inherent complexity of the problems it tackles,
      developmental biology has produced one of the most spectacular conceptual
      achievements, demonstrating that embryos are built with conserved molecules that
      orchestrate pattern and morphogenesis. As the logic of development now emerges,
      new challenges arise, such as how tissue mechanics is controlled. Quantitative
      approaches and computational models are essential to predict tissue organization
      and cell shapes. I review briefly how physical concepts have fueled this research
      in the past decades.

PMID- 19404477
TI  - Mutational spaces for leaf shape and size.
AB  - A key approach to understanding how genes control growth and form is to analyze
      mutants in which shape and size have been perturbed. Although many mutants of
      this kind have been described in plants and animals, a general quantitative
      framework for describing them has yet to be established. Here we describe an
      approach based on Principal Component Analysis of organ landmarks and outlines.
      Applying this method to a collection of leaf shape mutants in Arabidopsis and
      Antirrhinum allows low-dimensional spaces to be constructed that capture the key
      variations in shape and size. Mutant phenotypes can be represented as vectors in
      these allometric spaces, allowing additive gene interactions to be readily
      described. The principal axis of each allometric space reflects size variation
      and an associated shape change. The shape change is similar to that observed
      during the later stages of normal development, suggesting that many phenotypic
      differences involve modulations in the timing of growth arrest. Comparison
      between allometric mutant spaces from different species reveals a similar range
      of phenotypic possibilities. The spaces therefore provide a general quantitative
      framework for exploring and comparing the development and evolution of form.

PMID- 19404479
TI  - Applications of signal processing techniques to bioinformatics, genomics, and
      proteomics.

PMID- 19404476
TI  - From DNA nanotechnology to synthetic biology.
AB  - Attempts to construct artificial systems from biological molecules such as DNA
      and RNA by self-assembly are compatible with the recent development of synthetic
      biology. Genetic mechanisms can be used to produce or control artificial
      structures made from DNA and RNA, and these structures can in turn be used as
      artificial gene regulatory elements, in vitro as well as in vivo. Artificial
      biochemical circuits can be incorporated into cell-like reaction compartments,
      which opens up the possibility to operate them permanently out of equilibrium. In
      small systems, stochastic effects become noticeable and will have to be accounted
      for in the design of future systems.

PMID- 19404475
TI  - Coupling between neuronal activity and microcirculation: implications for
      functional brain imaging.
AB  - In the neocortex, neurons with similar response properties are often clustered
      together in column-like structures, giving rise to what has become known as
      functional architecture-the mapping of various stimulus feature dimensions onto
      the cortical sheet. At least partially, we owe this finding to the availability
      of several functional brain imaging techniques, both post-mortem and in-vivo,
      which have become available over the last two generations, revolutionizing
      neuroscience by yielding information about the spatial organization of active
      neurons in the brain. Here, we focus on how our understanding of such functional
      architecture is linked to the development of those functional imaging
      methodologies, especially to those that image neuronal activity indirectly,
      through metabolic or haemodynamic signals, rather than directly through
      measurement of electrical activity. Some of those approaches allow exploring
      functional architecture at higher spatial resolution than others. In particular,
      optical imaging of intrinsic signals reaches the striking detail of approximately
      50 mum, and, together with other methodologies, it has allowed characterizing the
      metabolic and haemodynamic responses induced by sensory-evoked neuronal activity.
      Here, we review those findings about the spatio-temporal characteristics of
      neurovascular coupling and discuss their implications for functional brain
      imaging, including position emission tomography, and non-invasive neuroimaging
      techniques, such as funtional magnetic resonance imaging, applicable also to the
      human brain.

PMID- 19404480
TI  - Simple use of the suppository type povidone-iodine can prevent infectious
      complications in transrectal ultrasound-guided prostate biopsy.
AB  - Purpose. To determine the effect of simple use of suppository povidone-iodine on
      infectious complications after transrectal ultrasonography-guided biopsy of the
      prostate. Methods. All 481 patients are included and received antibiotic
      prophylaxis. Among them, 360 patients received povidone-iodine suppository
      (Gynobetadine; 200 mg) immediately prior to biopsy and 121 patients did not.
      Infectious complications were classified. To evaluate bactericidal effects, we
      counted bacterial colonies in the rectum, harvested from a rectal swab before
      insertion of the suppository and after biopsy. Aliquots of the suspended
      bacterial strains were added to Mueller-Hinton agar medium for incubation. Colony
      counts were determined. Results. Infectious complications developed in 1 case
      (0.3%) in the rectal preparation group (Group 1) and in 8 cases (6.6%) in the
      nonrectal preparation group (Group 2). One in Group 1 had a fever without sepsis.
      Two patients had sepsis and six had fever without sepsis in Group 2. Rectal
      preparation was a statistically significant risk factor influencing the
      development of infectious complications. In vitro experiments, the mean number of
      colony-forming units decreased 99.9% after the rectal povidone-iodine
      preparation. Conclusions. All through the biopsy, povidone-iodine melted into the
      rectum and decreased the bacterial colony count. Simple use of povidone-iodine
      suppository before prostate biopsy minimizes the risk of infectious
      complications.

PMID- 19404482
TI  - MBX-102/JNJ39659100, a novel non-TZD selective partial PPAR-gamma agonist lowers
      triglyceride independently of PPAR-alpha activation.
AB  - MBX-102/JNJ-39659100 (MBX-102) is a selective, partial PPAR-gamma agonist that
      lowers glucose in the absence of some of the side effects, such as weight gain
      and edema, that are observed with the TZDs. Interestingly MBX-102 also displays
      pronounced triglyceride lowering in preclinical rodent models and in humans.
      Although in vitro reporter gene studies indicated that MBX-102 acid is a highly
      selective PPAR-gamma agonist that lacks PPAR-alpha activity, we sought to
      determine if PPAR-alpha activation in vivo could possibly contribute to the
      triglyceride lowering abilities of MBX-102. In vivo studies using ZDF and ZF rats
      demonstrated that MBX-102 lowered plasma triglycerides. However in ZF rats, MBX
      102 had no effect on liver weight or on hepatic expression levels of PPAR-alpha
      target genes. Further in vitro studies in primary human hepatocytes supported
      these findings. Finally, the ability of MBX-102 to lower triglycerides was
      maintained in PPAR-alpha knockout mice, unambiguously establishing that the
      triglyceride lowering effect of MBX-102 is PPAR-alpha independent. The in vivo
      lipid lowering abilities of MBX-102 are therefore mediated by an alternate
      mechanism which is yet to be determined.

PMID- 19404481
TI  - Immunohistochemical localization of the bradykinin B1 and B2 receptors in human
      nasal mucosa.
AB  - Bradykinin (BK) has been tobe thought a potent mediator involved in allergic
      rhinitis because BK was recovered from the nasal lavage fluid of allergic
      rhinitis patients after allergen provocation and BK receptor antagonists relief
      nasal allergic symptoms. Two mammalian BK receptor subtypes, B1 and B2, have been
      defined based on their pharmacological properties. We investigated the
      localization of these receptors by immunohistochemistry. Human turbinates were
      obtained after turbinectomy from 12 patients with nasal obstruction refractory to
      medical therapy. The immunohistochemical study revealed that epithelial cells,
      submucosal glands, fibroblast, vascular smooth muscle, vascular endothelial
      cells, and macrophages showed immunoreactivity for both B1 and B2 receptors. The
      B2 receptor expression was found in peripheral nerve fibers, whereas the B1
      expression was not observed in nerves. The results may have an important clinical
      implication for understanding the differential roles of BK receptor subtypes on
      upper airway diseases such as allergic rhinitis and nonallergic rhinitis.

PMID- 19404484
TI  - Clustering of gene expression data based on shape similarity.
AB  - A method for gene clustering from expression profiles using shape information is
      presented. The conventional clustering approaches such as K-means assume that
      genes with similar functions have similar expression levels and hence allocate
      genes with similar expression levels into the same cluster. However, genes with
      similar function often exhibit similarity in signal shape even though the
      expression magnitude can be far apart. Therefore, this investigation studies
      clustering according to signal shape similarity. This shape information is
      captured in the form of normalized and time-scaled forward first differences,
      which then are subject to a variational Bayes clustering plus a non-Bayesian
      (Silhouette) cluster statistic. The statistic shows an improved ability to
      identify the correct number of clusters and assign the components of cluster.
      Based on initial results for both generated test data and Escherichia coli
      microarray expression data and initial validation of the Escherichia coli
      results, it is shown that the method has promise in being able to better cluster
      time-series microarray data according to shape similarity.

PMID- 19404483
TI  - Statistical analysis of microarray data with replicated spots: a case study with
      synechococcus WH8102.
AB  - Until recently microarray experiments often involved relatively few arrays with
      only a single representation of each gene on each array. A complete genome
      microarray with multiple spots per gene (spread out spatially across the array)
      was developed in order to compare the gene expression of a marine cyanobacterium
      and a knockout mutant strain in a defined artificial seawater medium. Statistical
      methods were developed for analysis in the special situation of this case study
      where there is gene replication within an array and where relatively few arrays
      are used, which can be the case with current array technology. Due in part to the
      replication within an array, it was possible to detect very small changes in the
      levels of expression between the wild type and mutant strains. One interesting
      biological outcome of this experiment is the indication of the extent to which
      the phosphorus regulatory system of this cyanobacterium affects the expression of
      multiple genes beyond those strictly involved in phosphorus acquisition.

PMID- 19404485
TI  - Asymmetric Synthesis of (+)-Iso-6-Cassine via Stereoselective Intramolecular
      Amidomercuration.
AB  - The first asymmetric synthesis of (+)-iso-6-cassine is described. Lipase
      catalyzed resolution, enantioselective Overman rearrangement, and
      diastereoselective intramolecular amidomercuration were used for the installation
      of the three stereocenters in (+)-iso-6-cassine, and cross-metathesis was
      employed for the attachment of the side-chain.

PMID- 19404486
TI  - Overexpression of nuclear transport factor 2 may protect against diabetic
      retinopathy.
AB  - PURPOSE: We performed human, animal, and in vitro studies to examine the
      potential role of nuclear transport factor 2 (NTF2) in conferring resistance to
      diabetic retinopathy (DR). METHODS: Blood NTF2 levels were assessed in two groups
      of patients with type 2 diabetes mellitus. Group P patients had a history of
      proliferative DR (PDR), while group N patients did not. The retinal vasculature
      was examined in diabetic rats three months after they received an intravitreal
      injection of a recombinant adeno-associated virus (rAAV) vector overexpressing
      NTF2 (rAAV2-NTF2). Control rats were treated with rAAV2 only. Rat retinal
      capillary endothelial cells (RRCECs) were infected with rAAV2-NTF2, or with a
      vector expressing siRNA targeted against NTF2, to assess the effects of
      overexpression and inhibition of NTF2 on vascular endothelial growth factor
      (VEGF) expression (mRNA and protein). RESULTS: There was a strong trend for
      patients with DR to have lower blood NTF2 levels compared to those who did not
      have DR (0.10+/-0.01 versus 0.20+/-0.08, p=0.079). There was significantly less
      retinal blood vessel leakage in diabetic rats infected with rAAV2-NTF2 compared
      to controls (16.5+/-2.9 versus 24.7+/-7.3, p=0.039). These rats exhibited normal
      retinal vasculature and blood-retinal barrier function. VEGF expression was
      inhibited by NTF2 overexpression and stimulated by NTF2 inhibition, (protein
      [0.41+/-0.05 versus 0.23+/-0.06] and mRNA [0.37+/-0.04 versus 0.23+/-0.06] p<0.01
      for all). CONCLUSIONS: These finding suggest that NTF2 is a potential mediator of
      retinal vasculature integrity. NTF2 may act by altering VEGF expression, thereby
      influencing the development of DR in patients with diabetes mellitus.

PMID- 19404487
TI  - Retinal oscillations carry visual information to cortex.
AB  - Thalamic relay cells fire action potentials that transmit information from retina
      to cortex. The amount of information that spike trains encode is usually
      estimated from the precision of spike timing with respect to the stimulus.
      Sensory input, however, is only one factor that influences neural activity. For
      example, intrinsic dynamics, such as oscillations of networks of neurons, also
      modulate firing pattern. Here, we asked if retinal oscillations might help to
      convey information to neurons downstream. Specifically, we made whole-cell
      recordings from relay cells to reveal retinal inputs (EPSPs) and thalamic outputs
      (spikes) and then analyzed these events with information theory. Our results show
      that thalamic spike trains operate as two multiplexed channels. One channel,
      which occupies a low frequency band (<30 Hz), is encoded by average firing rate
      with respect to the stimulus and carries information about local changes in the
      visual field over time. The other operates in the gamma frequency band (40-80 Hz)
      and is encoded by spike timing relative to retinal oscillations. At times, the
      second channel conveyed even more information than the first. Because retinal
      oscillations involve extensive networks of ganglion cells, it is likely that the
      second channel transmits information about global features of the visual scene.

PMID- 19404495
TI  - Making the case: solutions for tough times.

PMID- 19404497
TI  - A case study: using social tagging to engage students in learning Medical Subject
      Headings.
AB  - In exploring new ways of teaching students how to use Medical Subject Headings
      (MeSH), librarians at Boston University's Alumni Medical Library (AML) integrated
      social tagging into their instruction. These activities were incorporated into
      the two-credit graduate course, "GMS MS 640: Introduction to Biomedical
      Information," required for all students in the graduate medical science program.
      Hands-on assignments and in-class exercises enabled librarians to present MeSH
      and the concept of a controlled vocabulary in a familiar and relevant context for
      the course's Generation Y student population and provided students the
      opportunity to actively participate in creating their education. At the
      conclusion of these activities, students were surveyed regarding the clarity of
      the presentation of the MeSH vocabulary. Analysis of survey responses indicated
      that 46% found the concept of MeSH to be the clearest concept presented in the in
      class intervention.

PMID- 19404494
TI  - MAVS-mediated apoptosis and its inhibition by viral proteins.
AB  - BACKGROUND: Host responses to viral infection include both immune activation and
      programmed cell death. The mitochondrial antiviral signaling adaptor, MAVS (IPS
      1, VISA or Cardif) is critical for host defenses to viral infection by inducing
      type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses
      has not been elucidated. PRINCIPAL FINDINGS: We show that MAVS causes apoptosis
      independent of its function in initiating IFN-I production. MAVS-induced cell
      death requires mitochondrial localization, is caspase dependent, and displays
      hallmarks of apoptosis. Furthermore, MAVS(-/-) fibroblasts are resistant to
      Sendai virus-induced apoptosis. A functional screen identifies the hepatitis C
      virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV)
      nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly
      as a method of immune evasion. SIGNIFICANCE: This study describes a novel role
      for MAVS in controlling viral infections through the induction of apoptosis, and
      identifies viral proteins which inhibit this host response.

PMID- 19404498
TI  - Search strategies to identify information on adverse effects: a systematic
      review.
AB  - OBJECTIVES: The review evaluated studies of electronic database search strategies
      designed to retrieve adverse effects data for systematic reviews. METHODS:
      Studies of adverse effects were located in ten databases as well as by checking
      references, hand-searching, searching citations, and contacting experts. Two
      reviewers screened the retrieved records for potentially relevant papers.
      RESULTS: Five thousand three hundred thirteen citations were retrieved, yielding
      19 studies designed to develop or evaluate adverse effect filters, of which 3 met
      the inclusion criteria. All 3 studies identified highly sensitive search
      strategies capable of retrieving over 95% of relevant records. However, 1 study
      did not evaluate precision, while the level of precision in the other 2 studies
      ranged from 0.8% to 2.8%. Methodological issues in these papers included the
      relatively small number of records, absence of a validation set of records for
      testing, and limited evaluation of precision. CONCLUSIONS: The results indicate
      the difficulty of achieving highly sensitive searches for information on adverse
      effects with a reasonable level of precision. Researchers who intend to locate
      studies on adverse effects should allow for the amount of resources and time
      required to conduct a highly sensitive search.

PMID- 19404499
TI  - Development of a new academic digital library: a study of usage data of a core
      medical electronic journal collection.
AB  - OBJECTIVES: The current study evaluates the results of a previously reported
      method for creating a core medical electronic journal collection for a new
      medical school library, validates the core collection created specifically to
      meet the needs of the new school, and identifies strategies for making cost
      effective e-journal selection decisions. METHODS: Usage data were extracted for
      four e-journal packages (Blackwell-Synergy, Cell Press, Lippincott Williams &
      Wilkins, and ScienceDirect). Usage was correlated with weighted point values
      assigned to a core list of journal titles, and each package was evaluated for
      relevancy and cost-effectiveness to the Florida State University College of
      Medicine (FSU COM) population. RESULTS: The results indicated that the
      development of the core list was a valid method for creating a new twenty-first
      century, community-based medical school library. Thirty-seven journals are
      identified for addition to the FSU COM core list based on use by the COM, and
      areas of overlapping research interests between the university and the COM are
      identified based on use of specific journals by each population. CONCLUSIONS: The
      collection development approach that evolved at the FSU COM library was useful
      during the initial stages of identifying and evaluating journal selections and in
      assessing the relative value of a particular journal package for the FSU COM
      after the school was established.

PMID- 19404500
TI  - A bibliometric analysis of the scientific literature on Internet, video games,
      and cell phone addiction.
AB  - OBJECTIVES: The aim of this study was to locate the scientific literature dealing
      with addiction to the Internet, video games, and cell phones and to characterize
      the pattern of publications in these areas. METHODS: One hundred seventy-nine
      valid articles were retrieved from PubMed and PsycINFO between 1996 and 2005
      related to pathological Internet, cell phone, or video game use. RESULTS: The
      years with the highest numbers of articles published were 2004 (n = 42) and 2005
      (n = 40). The most productive countries, in terms of number of articles
      published, were the United States (n = 52), China (n = 23), the United Kingdom (n
      = 17), Taiwan (n = 13), and South Korea (n = 9). The most commonly used language
      was English (65.4%), followed by Chinese (12.8%) and Spanish (4.5%). Articles
      were published in 96 different journals, of which 22 published 2 or more
      articles. The journal that published the most articles was Cyberpsychology &
      Behavior (n = 41). Addiction to the Internet was the most intensely studied
      (85.3%), followed by addiction to video games (13.6%) and cell phones (2.1%).
      CONCLUSIONS: The number of publications in this area is growing, but it is
      difficult to conduct precise searches due to a lack of clear terminology. To
      facilitate retrieval, bibliographic databases should include descriptor terms
      referring specifically to Internet, video games, and cell phone addiction as well
      as to more general addictions involving communications and information
      technologies and other behavioral addictions.

PMID- 19404501
TI  - The great contribution: Index Medicus, Index-Catalogue, and IndexCat.
AB  - OBJECTIVE: The systematic indexing of medical literature by the Library of the
      Surgeon-General's Office (now the National Library of Medicine) has been called
      "America's greatest contribution to medical knowledge." In the 1870s, the library
      launched two indexes: the Index Medicus and the Index-Catalogue of the Library of
      the Surgeon-General's Office. Index Medicus is better remembered today as the
      forerunner of MEDLINE, but Index Medicus began as the junior partner of what the
      library saw as its major publication, the Index-Catalogue. However, the Index
      Catalogue had been largely overlooked by many medical librarians until 2004, when
      the National Library of Medicine released IndexCat, the online version of Index
      Catalogue. Access to this huge amount of material raised new questions: What was
      the coverage of the Index-Catalogue? How did it compare and overlap with the
      Index Medicus? METHOD: Over 1,000 randomly generated Index Medicus citations were
      cross-referenced in IndexCat. RESULTS: Inclusion, form, content, authority
      control, and subject headings were evaluated, revealing that the relationship
      between the two publications was neither simple nor static through time. In
      addition, the authors found interesting anomalies that shed light on how medical
      literature was selected and indexed in "America's greatest contribution to
      medical knowledge."

PMID- 19404502
TI  - Web usability testing with a Hispanic medically underserved population.
AB  - OBJECTIVES: Skilled website developers value usability testing to assure user
      needs are met. When the target audience differs substantially from the
      developers, it becomes essential to tailor both design and evaluation methods. In
      this study, researchers carried out a multifaceted usability evaluation of a
      website (Healthy Texas) designed for Hispanic audiences with lower computer
      literacy and lower health literacy. METHODS: METHODS INCLUDED: (1) heuristic
      evaluation by a usability engineer, (2) remote end-user testing using WebEx
      software; and (3) face-to-face testing in a community center where use of the
      website was likely. RESULTS: Researchers found standard usability testing methods
      needed to be modified to provide interpreters, increased flexibility for time on
      task, presence of a trusted intermediary such as a librarian, and accommodation
      for family members who accompanied participants. Participants offered
      recommendations for website redesign, including simplified language, engaging and
      relevant graphics, culturally relevant examples, and clear navigation.
      CONCLUSIONS: User-centered design is especially important when website developers
      are not representative of the target audience. Failure to conduct appropriate
      usability testing with a representative audience can substantially reduce use and
      value of the website. This thorough course of usability testing identified
      improvements that benefit all users but become crucial when trying to reach an
      underserved audience.

PMID- 19404504
TI  - Partnering to promote service continuity in the event of an emergency: a
      successful collaboration between two interlibrary loan departments.

PMID- 19404503
TI  - Disappearing act: decay of uniform resource locators in health care management
      journals.
AB  - OBJECTIVES: This study examines the problem of decay of uniform resource locators
      (URLs) in health care management journals and seeks to determine whether
      continued availability at a given URL relates to the date of publication, the
      type of resource, or the top-level URL domain. METHODS: The authors determined
      the availability of web-based resources cited in articles published in five
      source journals from 2002 to 2004. The data were analyzed using correlation, chi
      square, and descriptive statistics. Attempts were made to locate the unavailable
      resources. RESULTS: After checking twice, 49.3% of the original 2,011 cited
      resources could not be located at the cited URL. The older the article, the more
      likely that URLs in the reference list of that article were inactive (r = -0.62,
      P<0.001, n = 1,968). There was no difference in availability across resource
      types (chi(2) = 5.28, df = 2, P = 0.07, n = 1,786). Whether an URL was active
      varied by top-level domain (chi(2) = 14.92, df = 4, P = 0.00, n = 1,786).
      CONCLUSIONS: URL decay is a serious problem in health care management journals.
      In addition to using website archiving tools like WebCite, publishers should
      require authors to both keep copies of Internet-based information they used and
      deposit copies of data with the publishers.

PMID- 19404505
TI  - The Research Imperative: Medical Library Association policy and the curricula of
      schools of library and information science.

PMID- 19404506
TI  - Medical librarians' uses and perceptions of social tagging.

PMID- 19404507
TI  - Embedded librarians: one library's model for decentralized service.

PMID- 19404508
TI  - Accuracy of references in the ophthalmic literature.

PMID- 19404510
TI  - Health literacy: an exploratory bibliometric analysis, 1997-2007.

PMID- 19404509
TI  - Liaison librarian tiers: levels of service.

PMID- 19404512
TI  - Spontaneous disappearance of high titre factor VIII inhibitor 15 years after
      unsuccessful ITI.
AB  - The most serious complication of haemophilia A is development of a high-titre
      factor VIII (FVIII) inhibitor which renders the patient unresponsive to FVIII
      replacement. Bleeding complications can only be controlled using FVIII-inhibitor
      bypassing agents but their effect is less certain. The ultimate goal is to
      eliminate the inhibitor by immune tolerance induction therapy (ITI) using daily
      high doses of FVIII. The success rate of ITI using various protocols is between
      56 and 79% (1, 2). If ITI is unsuccessful, the inhibitor usually persists
      throughout life. We report on a patient with a high titre FVIII inhibitor that
      persisted after ITI but spontaneously disappeared 15 years later.

PMID- 19404511
TI  - [Relevance of a single dose of 270 microg/kg recombinant factor VIIa for the
      treatment of patients with haemophilia and inhibitors - Recommendations from the
      GTH experts].
AB  - Recombinant factor VIIa (rFVIIa; NovoSeven) is, besides other indications,
      authorised for the treatment of bleeding episodes in patients with hereditary
      haemophilia A or B and inhibitors. Based on the results of three clinical
      studies, marketing authorisation was granted for the single dose of 270 microg/kg
      body weight rFVIIa for the treatment of mild to moderate bleeding episodes in
      patients with haemophilia A or B with inhibitors in March 2007. Thereupon, an
      expert group analysed the relevance of this additional treatment option for
      clinical routine. Compared with the repeated application of 90 microg/kg body
      weight rFVIIa, quality of life may be improved if the single dose of 270
      microg/kg body weight rFVIIa reduces the number of injections. The single dose
      has a benefit for those patients who require several rFVIIa applications or who
      do not respond adequately to low doses. Moreover, patients with poor venous
      access or patients who fear injections or reject them (especially children) may
      benefit from the single dose. The prescription of 270 microg/kg body weight
      rFVIIa as a single dose instead of multiple dosing of 90 microg/kg body weight is
      basically an individual and indication-related decision.

PMID- 19404513
TI  - Lepirudin treatment in a boy with suspected HIT II after surgery because of
      tetralogy of Fallot.
AB  - Heparin-induced thrombocytopenia (HIT II) in childhood is rare. Suspected HIT II
      requires immediate diagnostic and therapeutic measures in order to avoid
      potentially life threatening complications. Heparin must be stopped immediately.
      We report on a 6-year old boy who required cardiac surgery due to tetralogy of
      Fallot. To our knowledge he had been exposed to heparin for the first time during
      cardiac catheterization on the day before surgery. Preoperatively, platelet count
      was normal. Postoperatively (3 days after heparin exposure), he developed
      pulmonary and renal failure and required inotropic cardiac support and dialysis.
      He also developed progressive (severe) thrombocytopenia under heparin therapy on
      day 2-3 postoperatively. The dialysis filter required daily exchanges due to
      clotting despite increasing heparin doses. The first ELISA for HIT on postop day
      4 was negative. 3 days later a repeated test was positive. Von Willebrand factor
      antigen and D-dimers were markedly increased. The patient was immediately
      switched to lepirudin and subsequently stabilized slowly. No major systemic
      thrombosis occurred. After lepirudin treatment for 6 weeks the patient was fully
      recovered and HIT II-testing was negative again. CONCLUSION: In children with
      progressive thrombocytopenia in the setting of heparin exposure and signs of
      major or micro thrombosis HIT II must be ruled out. Even if a first early test
      turns out negative repeated testing should be performed. Lepirudin
      anticoagulation is effective and should be monitored correctly. Platelet
      transfusion should be avoided in HITII.

PMID- 19404514
TI  - [Clinical and laboratory aspects of the Aspirin-like defect as hereditary
      thrombocytopathy].
AB  - The Aspirin-like defect (ALD) is caused by defects in the intraplatelet
      arachidonic acid (AA)-metabolism. We here present the characteristics of a larger
      cohort in a single centre. PATIENTS, METHODS: Based on 17 ALD index patients
      bleeding symptoms, agonist-induced platelet aggregation and closure times in the
      PFA-100 test were analysed in a family cohort of altogether 52 individuals from
      17 families. Absent aggregation to AA (maximal aggregation <or= 10%) was the main
      diagnostic criterion. A mild ALD was diagnosed when aggregation was 11-40%.
      RESULTS: In addition to 17 ALD index patients, 13 family members displayed ALD. 4
      family members were diagnosed with a mild ALD. Epistaxis, easy bruising,
      menorrhagia and perioperative hemorrhage were the most common bleeding symptoms,
      whereas three quarters of ALD patients presented with >or=1 bleeding symptoms.
      CONCLUSION: In case of a bleeding tendency diagnostic procedures should rule out
      primary haemostatic defects. Hereditary platelet function defects including ALD
      are an important differential diagnosis. Family studies are reasonable.

PMID- 19404515
TI  - Coagulation testing in the evaluation of suspected child abuse.
AB  - Every year in Germany nearly 3000 cases of child abuse were reported. When
      children are presented at emergency units with suspicious injuries and bruises a
      detailed documentation an evaluation is necessary after emergency treatment. As
      differential diagnosis inherited or acquired bleeding disorders should be
      excluded. In addition to a detailed evaluation of personal and family history and
      a physical evaluation different coagulation test to exclude defects of primary
      and secondary hemostasis should be performed. Clinician must know the limitations
      of these tests and keep in mind that an abnormal coagulation test does not
      exclude child abuse. Coagulation defects may be the consequence of child abuse
      and neglect or the two conditions may coexist.

PMID- 19404516
TI  - Identification of a novel factor X deletion in combination with a missense
      mutation in the F10 gene - Genotype-phenotype correlation in a girl with severe
      factor X deficiency.
AB  - The genotype-phenotype relationship of compound heterozygous factor X deficiency
      in a young girl with severe factor X deficiency and bleeding symptoms is
      characterized. We identified a novel deletion of exon 6 and a missense mutation
      (c.856G>A, Val286Met) in exon 7 of the F10 gene leading to a compound
      heterozygous state and causing severe factor X deficiency. Therapeutic options
      for patients with symptomatic factor X deficiency are demonstrated.

PMID- 19404517
TI  - A large Swiss family with Bernard-Soulier syndrome - Correlation phenotype and
      genotype.
AB  - Bernard-Soulier syndrome (BSS) is a rare, autosomal recessive inherited bleeding
      disorder associated with thrombocytopenia, thrombocytopathy and giant platelets.
      BSS is caused by genetic alterations of the glycoprotein (GP) Ib/V/IX complex. We
      report on a large Swiss family of whom four family members suffer from BSS. Here,
      a homozygous missense mutation in position 1829 (A(R)G) of the GPIX gene
      constituting a N45S substitution is the cause for the bleeding symptoms. A total
      of 38 family members within two generations were analyzed regarding the N45S
      mutation by DNA sequencing and restriction fragment length polymorphism. The
      laboratory parameters which are characteristically for BSS such as platelet
      count, platelet volume and the expression of CD42a (GPIX), CD42b (GPIbalpha) and
      CD41 (GPIIb) were measured for all 38 individuals. The four homozygous patients
      showed bleeding symptoms, thrombocytopenia and giant platelets. In these
      patients, the expression of CD42a (GPIX), CD42b (GPIbalpha) was diminished.
      Interestingly, the intensity of the bleeding symptoms of the 4 homozygous family
      members seemed to vary although they carry the same mutation. The 24 heterozygous
      carriers did not differ significantly from their 10 wildtype family members
      regarding bleeding symptoms and laboratory analysis.

PMID- 19404518
TI  - Acquired von Willebrand syndrome as side effect of valproic acid therapy in
      children is rare.
AB  - To determine the frequency and clinical relevance of acquired von Willebrand
      syndrome (aVWS) due to antiepileptic therapy by valproic acid, we investigated 50
      consecutive children in three neuropediatric institutions. Coagulation factors
      were determined in local laboratories before and three times after starting
      therapy with valproic acid. Parameters of von Willebrand factor (VWF) were
      additionally investigated in a reference laboratory including multimeric
      analysis. Significant changes in the coagulation system were found concerning
      fibrinogen (decreased from 287 +/- 70 mg/dl to 222 +/- 67 mg/dl; p < 0.001) and
      platelet count. Changes of VWF parameters were also found but no patient
      developed laboratory defined aVWS. We conclude that the bleeding tendency
      observed in some children undergoing antiepileptic therapy with valproic acid is
      not due to aVWS.

PMID- 19404519
TI  - ITI with high-dose FIX and combined immunosuppressive therapy in a patient with
      severe haemophilia B and inhibitor.
AB  - Inhibitor development is a rare but serious event in hemophilia B patients.
      Management is hampered by the frequent occurrence of allergic reactions to factor
      IX, low success rates of current inhibitor elimination protocols and the risk of
      development of nephrotic syndrome. Single cases of immune tolerance induction
      (ITI) including immunosuppressive agents like mycophenolat mofetil (MMF) or
      rituximab have been reported. We present a case of successful inhibitor
      elimination with a combined immune-modulating therapy and high-dose factor IX
      (FIX). This boy had developed a FIX inhibitor at the age of 5 years and had a
      history of allergic reactions to FIX and to FEIBAO. Under on-demand treatment
      with recombinant activated FVII the inhibitor became undetectable but the boy
      suffered from multiple joint and muscle bleeds. At the age of 11.5 years ITI was
      attempted with a combination of rituximab, MMF, dexamethasone, intravenous
      immunoglobulins and high-dose FIX. The inhibitor did not reappear and FIX half
      life normalized. No allergic reaction, no signs of nephrotic syndrome and no
      serious infections were observed.

PMID- 19404520
TI  - The problem of novel FVIII missense mutations for haemophilia A genetic
      counseling.
AB  - Molecular genetic testing for factor VIII (FVIII) mutations is indicated in
      haemophilia A since determination of FVIII activity cannot reliably identify
      female carriers. Given the large number of FVIII mutations the identification of
      novel mutations is not uncommon. Since amino acid polymorphisms of FVIII are
      rare, missense mutations in patients with haemophilia A which are not found in
      the normal population are considered as causative in general practice when no
      other mutation can be detected by complete FVIII gene sequencing. We report a
      novel rare missense variant (P2311S) in a haemophilia A family that was
      mistakenly considered as pathogenic leading to amniocentesis, prenatal diagnosis
      and influenced the peripartal management of the putatively affected child.
      Subsequently, we identified the novel causative mutation V197G in the family's
      index case which could be detected neither in the neonate nor in his mother.
      CONCLUSION: This case emphasizes the necessity to establish the molecular
      diagnosis in the family's index case and to perform expression studies of novel
      mutations to prove their causative nature.

PMID- 19404521
TI  - Reassessment of treatment modalities for paediatric patients with chronic immune
      thrombocytopenia.
AB  - Approximately 70% of children have the acute form of immune thrombocytopenia
      (ITP), which is defined by recovery within six months of presentation with or
      without treatment. Chronic ITP is to be reserved for patients with platelets <
      100000/microl for more than twelve months and exclusion of other diagnosis like
      systemic lupus erythematosus or bone marrow failures. In children, the chance of
      spontaneous recovery is 52% after diagnosis of chronic ITP. The Intercontinental
      Childhood ITP Study group recommends that children without bleeding may not
      require therapy regardless of their platelet count. Whereas in patients with
      bleeding symptoms first line therapy is defined and includes steroids or
      immunoglobuline, second line therapy in refractory patients with significant
      hemorrhagic problems is unclear. Guidelines recommend splenectomy, but for more
      than 50 years patients and physicians look for pharmacological alternatives. It
      may be that rituximab is a promising option which has been proven to be effective
      with few adverse effects. Till now the treatment has focused on immunomodulation.
      Research has now focused on stimulating platelet production. In this review we
      discuss old and new therapy modalities for children with cITP.

PMID- 19404522
TI  - Inhibitor treatment by rituximab in congenital haemophilia A - Two case reports.
AB  - The development of neutralizing alloantibodies (inhibitors) to factor VIII
      (FVIII) is one of the most serious complications in the treatment of
      haemophiliacs. Inhibitors occur in approximately 20 to 30% of previously
      untreated patients (PUPs), predominantly children, with severe haemophilia A
      within the first 50 exposure days (ED). Immune tolerance induction (ITI) leads to
      complete elimination of the inhibitor in up to 80% of the patients and offers the
      possibility to restore regular FVIII prophylaxis. However, patients with high
      titre inhibitors, in whom standard ITI fails, usually impose with high morbidity
      and mortality and therefore prompting physicians to alternate therapy regimens.
      Rituximab, an anti-CD 20 monoclonal antibody has been successfully used in
      children and adults for the management of B-cell mediated disorders. We report on
      the use of a new protocol including rituximab in two adolescents with severe
      haemophilia A and high titre inhibitors, severe bleeding tendency and high
      clotting factor consumption after failing standard ITI. Both patients received a
      concomitant treatment with FVIII according to the Bonn protocol, cyclosporine A
      and immunoglobulin. Treatment with rituximab resulted in a temporary B-cell
      depletion leading to the disappearance of the inhibitor. FVIII recovery and half
      life turned towards normal ranges. In patient 1 the inhibitor reappeared 14
      months after the last rituximab administration. In patient 2 complete immune
      tolerance could be achieved for 60 months. Bleeding frequency diminished
      significantly and clinical joint status improved in both patients. In patient 1
      the treatment course was complicated by aspergillosis and hepatitis B infection.
      CONCLUSION: Rituximab may be favourable for patients with congenital haemophilia,
      high-titre inhibitors and a severe clinical course in whom standard ITI has
      failed. Prospective studies are required to determine safety, efficacy and
      predictors of success.

PMID- 19404523
TI  - [Contraception and thrombophilia].
AB  - The risk of thromboembolic events (TE) is increased by acquired or inherited
      thrombophilias (IT). We know that some hormonal contraceptives also increase the
      risk of thrombosis, thus, the use of such contraceptives are discussed as
      contraindications in women with IT. TEs are infrequent events in children and
      adolescents and in the majority of cases are associated with secondary
      complications from underlying chronic illness. Although adolescents are not
      typically considered to be at high-risk for TE, this cohort is frequently using
      hormonal contraception, leading to an increased risk in cases with unknown IT.
      The risk of TE with pregnancy alone is higher than associated with combined
      hormonal contraception. Progestin-only methods have not been found to increase
      the risk of TE with only moderate changes of coagulation proteins compared to
      normal reference values. CONCLUSION: Thrombophilic women are good candidates for
      progestin-only contraceptive methods.

PMID- 19404525
TI  - [Severe prekallikrein deficiency due to a compound heterozygosis in the KLKB1
      gene].
AB  - A 14 year old boy was referred to us for a detailed coagulation study because a
      previously performed aPTT has been found prolonged. The boy had no history of
      bleeding symptoms and also the family history was negative for bleeding or
      thrombotic events. The aPTT in the patient was 96 s (reference range: 24-36 s),
      prothrombin time and thrombin time were both normal. As the cause for the
      prolonged aPTT we identified a severe prekallikrein deficiency (prekallikrein
      activity < 1%). The prekallikrein deficiency results from two mutations in the
      KLKB 1-gene: first, an insertion of 1 bp in codon 149 in exon 5 and, second, a
      base exchange Cys 548 (TGC) > Tyr (TAC) in exon 14. The boy inherited the first
      mutation from his father and the second from his mother. The mutation in the
      paternal allele was not described before the completion of our study. There are
      two brothers of the propositus, one with normal prekallikrein activity and no
      mutations in the KLKB1-gene, the other showed the same constellation as the
      propositus.

PMID- 19404524
TI  - Response to DDAVP in children with von Willebrand disease type 2.
AB  - We have prospectively evaluated the biologic response to desmopressin (DDAVP) in
      28 children with type 2 von Willebrand disease (VWD) in correlation with the
      phenotype and the molecular defect of VWF. The diagnosis of VWD type 2 was mainly
      based on VWF functional parameters and/or an aberrant VWF multimer pattern.
      Seventeen different mutations were identified (6 of them novel). No response with
      respect to the functional parameters VWF:RCo and/or VWF:CB was seen in patients
      with severe abnormality of the VWF multimer pattern. One patient with VWD type 2A
      phenotype IIC Miami did not respond with respect to VWF:CB, but showed a good
      response of VWF:Ag and FVIII:C as expected. Interestingly he showed a
      persistently high level of VWF:Ag and FVIII:C up to 4 hours after DDAVP infusion.
      Patients with minor alterations of multimer structure and particular mutations
      responded well to DDAVP, whereas patients with normal multimer structure but a
      defect in platelet dependent functional parameters did not respond with VWF:RCo.
      CONCLUSION: Children with VWD type 2 show a variable response to desmopressin
      depending on the mutation that correlates with the functional defect and the
      presence or absence as well as the half-life of large VWF multimers. Our data
      emphasize the usefulness of DDAVP testing even in patients with VWD type 2,
      possibly with the exception of VWD type 2B.

PMID- 19404526
TI  - Amniotic fluid embolism: the complication of known pathomechanism but without
      pathogenetic therapy?

PMID- 19404527
TI  - Methodological issues affecting estimates of bleeding risks and consequences
      after venous thromboembolism.

PMID- 19404528
TI  - Hypergravity and microgravity influence haemostasis.

PMID- 19404529
TI  - Inflammatory markers for ischaemic stroke.

PMID- 19404530
TI  - Female gender is a risk factor for stroke and thromboembolism in atrial
      fibrillation patients.

PMID- 19404531
TI  - Role of antithrombin concentrate in treatment of hereditary antithrombin
      deficiency. An update.
AB  - Antithrombin (AT) functions as a potent natural anticoagulant and serine protease
      inhibitor that inactivates many enzymes in the coagulation cascade. Antithrombin
      also possesses antiinflammatory properties, many of which are mediated by its
      actions as an anticoagulant. Hereditary AT deficiency is a rare, underrecognised
      medical condition that is associated with inadequate endogenous anticoagulation
      thought to result from impaired inhibition of serine protease coagulation
      factors. Inherited as an autosomal dominant trait, congenital AT deficiency
      typically reduces functional AT levels to 40-60% of normal. As a result,
      individuals with hereditary AT deficiency have a > or = 50% lifetime risk of
      venous thromboembolism (VTE). Specifically, AT deficiency is associated with a
      three- to seven-fold higher risk of VTE compared with other thrombophilias. Thus,
      maintaining adequate levels of AT during high-risk periods is an important
      treatment goal. Long-term anticoagulant thromboprophylaxis is not recommended in
      asymptomatic patients with AT deficiency because of the increased risk of
      haemorrhage. However, treatment guidelines recommend short-term
      thromboprophylaxis in high-risk clinical settings, including surgery, trauma, and
      management of pregnancy, labour, and delivery. The goal of treatment for patients
      with hereditary AT deficiency is an initial increase in AT activity to > or =
      120% of normal levels followed by maintenance of AT activity at > or = 80% of
      normal levels. Plasma-derived AT, heparin, fresh frozen plasma, and human
      recombinant AT are treatment options for individuals with hereditary AT
      deficiency. The objective of this review is to discuss hereditary AT deficiency
      and the role of AT replacement therapy in the treatment of patients with this
      congenital disorder.

PMID- 19404532
TI  - Do common prothrombotic mutations influence the risk of cerebral ischaemia in
      patients with patent foramen ovale? Systematic review and meta-analysis.
AB  - Conflicting results are available on the association of prothrombotic genetic
      abnormalities with patent foramen ovale (PFO)-related cerebral ischaemia. We
      comprehensively sought and identified studies of the association of both the
      factor V Leiden (FV(G1691A) mutation) and the prothrombin mutation (PT(G20210A)
      mutation) with PFO-related cerebral ischaemia and did meta-analyses to assess the
      evidence for such a relation. We analysed data from six eligible studies in 856
      cases and 1,001 control subjects. Additional unpublished data from a new series
      including 463 subjects were also entered into the analysis. The PT(G20210A)
      variant was significantly associated with PFO-related stroke in comparison with
      both control subjects (odds ratio [OR] 3.85; 95% confidence interval [CI] 2.22 to
      6.66) and non-PFO-associated stroke patients (OR 2.31; 95% CI 1.20 to 4.43),
      whereas a trend toward an association was observed for the FV(G1691A) mutation
      (OR 1.18; 95% CI 0.73 to 1.90, compared to control subjects; OR 1.14; 95% CI 0.62
      to 2.09, compared to non-PFO-associated stroke patients). The status of carrier
      of either the FV(G1691A) mutation or the PT(G20210A) variant was associated with
      a risk for stroke of 1.98 (95% CI 1.38 to 2.83) and 1.62 (95% CI 1.03 to 2.57),
      as compared to control subjects and non-PFO-associated stroke patients,
      respectively. Addition of common prothrombotic genetic variants to standard
      initial screening may contribute to stratifying PFO-associated stroke patients at
      different risk of ischaemic events and targeting secondary prevention strategies.

PMID- 19404533
TI  - Plasma elimination kinetics for factor VII are independent of its activation to
      factor VIIa and complex formation with plasma inhibitors.
AB  - The mechanism for the elimination of factor VII (FVII) from the circulation is
      unknown, just as it is unclear how activation of FVII to FVIIa and subsequent
      complex formation with antithrombin III (AT) or alpha2-macroglobulin (alpha2M)
      affects clearance. The possibility that the clearance mechanism involves
      activation and inhibitor complex formation as obligatory intermediate reactions
      is examined in this study. Human and murine sera were spiked with human FVIIa in
      the absence and presence of heparin and analysed for complex formation. Complex
      formation in vivo was studied after intravenous injection of (125)I-VIIa in mice;
      and the pharmacokinetics (PK) of human and murine FVIIa was studied in normal
      mice. Furthermore, comparative PK studies were performed with FVII, FVIIa, active
      site blocked FVIIa and a preformed FVIIa-AT complex in normal and alpha2M
      deficient mice. The data demonstrated that FVIIa-AT complexes and to a much
      lesser extent FVIIa-alpha2M-complexes accumulated in vivo after FVIIa
      administration. FVIIa-AT accounted for about 50% of total FVIIa antigen left in
      the circulation after 3 hours. All FVII derivatives studied including FVII, FVIIa
      and FVIIa-AT were cleared with similar rates suggesting an elimination kinetics
      which is unaffected by FVII activation and subsequent inactivation by plasma
      inhibitors.

PMID- 19404534
TI  - In-vitro evaluation of anti-factor IXa aptamer on thrombin generation, clotting
      time, and viscoelastometry.
AB  - The REG1 system consists of factor IXa inhibitor, RB006, an aptamer-based
      anticoagulant and its antidote, RB007. The optimal use of RB006 can be
      facilitated by understanding its effect on the formation of thrombin and fibrin,
      and other standard tests of coagulation. Blood from consented volunteers was
      drawn into 3.2% citrate (9:1 v/v) and either used immediately or centrifuged to
      obtain platelet-poor plasma. Increasing concentrations of aptamer (6-24
      microg/ml) alone or in combination with heparin (0.1 U/ml) or lepirudin (0.2
      microg/ml) were added to blood and plasma samples. Activated clotting times
      (ACT+, low range-ACT), thrombelastometry (ROTEM) or thrombelastography (TEG) were
      performed in recalcified whole blood samples. Thrombin generation, prothrombin
      time (PT) and activated partial thromboplastin time (aPTT) were performed in
      plasma samples. To some samples the antidote RB007 was added to neutralise the
      anticoagulation activity of RB006. In all experiment the ratio of RB006 to RB007
      was kept 1:2. RB006 dose-dependently prolonged aPTT and low range-ACT, but, as
      expected, had no effect on PT. RB006 prolonged the lag time and decreased the
      peak of Actin-triggered thrombin generation. Thrombin-activated TEG demonstrated
      that RB006 decreases the rate of clot formation. These effects were potentiated
      when RB006 was combined with heparin or lepirudin. In all experiments RB007
      reversed the effects of RB006 back to baseline. In conclusion, RB006 inhibits
      thrombin generation and clot formation in a concentration-dependent manner. It is
      feasible to monitor RB006 and its reversal with RB007 using aPTT, low range-ACT,
      and thrombin-activated TEG.

PMID- 19404535
TI  - Epitope specificity of anti-factor VIII antibodies from inhibitor positive
      acquired and congenital haemophilia A patients using synthetic peptides spanning
      A and C domains.
AB  - Development of antibodies (Ab) that either block the function of coagulation
      factor VIII (FVIII) (inhibitors) or clear it from circulation, seriously
      complicate the treatment of haemophilia A patients with FVIII products.
      Autoantibodies which develop in subjects without congenital FVIII defects, cause
      acquired haemophilia, a rare but life-threatening coagulopathy. Identification of
      the FVIII epitopes to which inhibitor Abs bind will help understanding the
      mechanisms of inhibitor activity, and perhaps development of new therapies. Here,
      we examined the FVIII peptide sequence regions recognised by anti-FVIII Ab in the
      plasma of six congenital and one acquired haemophilia patients with high
      inhibitor titers (24.4-2000 BU/ml). We used indirect ELISA and overlapping
      synthetic peptides, 20 residues long, spanning the sequence of the A and C FVIII
      domains. None of the plasma samples reacted with A1, A3 or C1 domain peptides.
      Six plasmas reacted with A2 and/or C2 peptides. Peptides spanning residues A2-521
      690 and C2-2251-2332 were recognised most frequently and strongly. They include
      residues that contribute to the binding sites for activated factor IX and
      phosphatidyl serine/von Willebrand factor. These results suggest that anti-FVIII
      Abs share a pattern of antigen specificity in our panel of patients, and that
      exposed regions of the FVIII molecule that form functionally important binding
      sites elicit an intense Ab response.

PMID- 19404536
TI  - Coagulation factor XIII serves as protein disulfide isomerase.
AB  - Tissue transglutaminase was reported to act as protein disulfide isomerase (PDI).
      We studied whether plasma transglutaminase - coagulation factor XIII (FXIII) -
      has PDI activity as well. PDI activity was measured by determining the ability to
      renature reduced-denatured RNase (rdRNase). We found that FXIII can renature
      rdRNase, with efficiency comparable to commercial PDI. This PDI activity was
      inhibited by bacitracin. Like tissue transglutaminase, FXIII-mediated PDI
      activity is independent of its transglutaminase activity and is located on the A
      subunit. Surface-associated PDI has been previously shown to catalyse two
      distinct functions: transnitrosation with subsequent release of intracellular
      nitric oxide and disulfide bond rearrangement during platelet integrin ligation.
      Our results imply that FXIII-PDI activity may have a role in platelet function.

PMID- 19404537
TI  - Procoagulant activity and phosphatidylserine of amniotic fluid cells.
AB  - Amniotic fluid (AF) may induce disseminated intravascular coagulation (DIC) when
      it enters maternal circulation by breaching the placental-maternal circulation
      barrier. The precise mechanism of the procoagulant activity of AF is unclear, but
      tissue factor (TF) has been proposed to be the main cause. As one constituent of
      AF, AF cells accumulate and undergo apoptosis continuously. Therefore, we
      speculate that AF cells have procoagulant activity due to the externalisation of
      phosphatidylserine (PS). The present study aims to demonstrate that, in addition
      to TF, the PS that is externalised on AF cells is important for the procoagulant
      activity of AF. Ten AF samples from parturient women were analysed using
      lactadherin as the probe for PS. Anti-TF antibody also was used to identify TF
      and its associated coagulation functions in AF cells. Normal platelets,
      neutrophils, and lymphocytes were harvested as controls. Confocal microscopy and
      flow cytometry was used to assess PS expression on AF cells. The procoagulant
      activity of AF cells was demonstrated by a plasma coagulation assay and further
      confirmed by factor Xase/prothrombinase assays. PS and TF were present on most AF
      cells, providing substantial procoagulant activity. Furthermore, factor Xase and
      prothrombinase assays showed that AF cells substantially enforced the activation
      of factor X and prothrombin. PS on AF cells is an important procoagulant source
      for AF. Lactadherin is an ideal anticoagulant for inhibiting the procoagulant
      activity of AF cells.

PMID- 19404538
TI  - Acquired factor V inhibitor. A problem-based systematic review.
AB  - Acquired factor V(FV) inhibitors as a rare bleeding disorder, poses a formidable
      challenge to treating physicians with limited evidence to guide its management.
      We systematically reviewed our experience in Singapore and the published
      literature to determine possible answers to clinical questions formulated on the
      manifestation and best management of non-bovine thrombin and non-congenital
      acquired FV inhibitors. The incidence in Singapore was 0.09 cases per million
      person years (3 cases over 10 years). Seventy-three other cases meeting pre
      defined search criteria were found in the published literature. Bleeding occurred
      in 68.4% of these patients, with mucous membranes being the most common site.
      Intracranial and retroperitoneal bleeds carried the highest mortality. The
      mortality rate from bleeding was 12%. There was a tendency for FV levels and
      PT/aPTT prolongation to predict bleeding but not the inhibitor level. No
      consistently effective haemostatic agent could be determined, but platelet
      transfusion should probably be the first line therapy. Among bleeding patients,
      inhibitors tended to disappear faster with inhibitor elimination therapy (IET)
      compared to without IET (60 vs. 150 days, p=0.299). IET made no significant
      difference among non-bleeding patients (p=0.511) and is thus recommended for
      bleeding patients or those with high bleeding risk. Steroids as single agent IET
      was effective in the majority of patients. Logical management approaches may be
      drawn but are limited by small sample size, heterogeneity of reports, and
      potential publication bias. The inception of a comprehensive registry will
      provide more reliable data that may verify our findings.

PMID- 19404539
TI  - Influence of molecular weight of chemically sulfated citrus pectin fractions on
      their antithrombotic and bleeding effects.
AB  - Evaluated were the anticoagulant and antithrombotic activities, and bleeding
      effect of two chemically sulfated polysaccharides, obtained from citric pectin,
      with different average molar masses. Both low-molecular-weight (Pec-LWS, 3,600
      g/mol) and high-molecular-weight sulfated pectins (Pec-HWS, 12,000 g/mol) had
      essentially the same structure, consisting of a (1-->4)-linked alpha-D-GalpA
      chain with almost all its HO-2 and HO-3 groups substituted by sulfate. Both
      polysaccharides had anticoagulant activity in vitro, although Pec-HWS was a more
      potent antithrombotic agent in vivo, giving rise to total inhibition of venous
      thrombosis at a dose of 3.5 mg/kg body weight. Surprisingly, in contrast with
      heparin, Pec-HWS and Pec-LWS are able to directly inhibit alpha-thrombin and
      factor Xa by a mechanism independent of antithrombin (AT) and/or heparin co
      factor II (HCII). Moreover, Pec-HWS provided a lower risk of bleeding than
      heparin at a dose of 100% effectiveness against venous thrombosis, indicating it
      to be a promising antithrombotic agent.

PMID- 19404540
TI  - A long-lasting, plasmin-activatable thrombin inhibitor aids clot lysis in vitro
      and does not promote bleeding in vivo.
AB  - The leech protein hirudin is a potent inhibitor of thrombin, but clinical use of
      recombinant hirudin is restricted by haemorrhagic risks, and complicated by
      hirudin's rapid clearance from the circulation. We previously employed albumin
      fusion to slow hirudin variant 3 (HV3) clearance. In this study, we hypothesized
      that reconfiguration of the chimera, appending human serum albumin (HSA) to the N
      terminus of HV3, with an intervening plasmin cleavage site, would create a slowly
      cleared, plasmin-activatable HV3. Potential plasmin cleavage sites were screened
      by expression in Escherichia coli, interposed between glutathione
      sulfotransferase and HV3 domains. The most reactive sequence (GSGIYR-ITY) was
      recreated in C-terminally His-tagged albumin fusion protein HSACHV3, expressed in
      Pichia pastoris yeast and purified by nickel-chelate affinity chromatography.
      HSACHV3 showed no thrombin inhibitory activity in the absence of plasmin, but
      liberated active HV3 in a time- and concentration-dependent manner in its
      presence. In a discontinuous clot assay involving clot-bound thrombin, HSACHV3
      assisted clot lysis by limiting clot extension in a tPA- and concentration
      dependent manner. Similar results were obtained in plasma at higher
      concentrations of HSACHV3. The chimeric protein exhibited much slower clearance
      in mice than unfused HV3, and indistinguishable pharmacokinetics from unfused
      recombinant HSA. In a mouse tail transection bleeding model, doses of HSACHV3
      identical to those of HV3 that elicited a four-fold increase in the volume of
      shed blood were without effect. Our results suggest that HSACHV3 is a fully
      latent, plasmin activatable, long-lasting hirudin, of potential benefit in
      thrombotic disorders resistant to natural or pharmacological clot lysis.

PMID- 19404542
TI  - VIDAS D-dimer in combination with clinical pre-test probability to rule out
      pulmonary embolism. A systematic review of management outcome studies.
AB  - Clinical outcome studies have shown that it is safe to withhold anticoagulant
      therapy in patients with suspected pulmonary embolism (PE) who have a negative D
      dimer result and a low pretest probability (PTP) either using a PTP model or
      clinical gestalt. It was the objective of the present study to assess the safety
      of the combination of a negative VIDAS D-dimer result in combination with a non
      high PTP using the Wells or Geneva models to exclude PE. A systematic literature
      search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of
      Controlled Trials and all EBM Reviews. Seven studies (6 prospective management
      studies and 1 randomised controlled trial) reporting failure rates at three
      months were included in the analysis. Non-high PTP was defined as "unlikely"
      using the Wells' model, or "low/intermediate" PTP using either the Geneva score,
      the Revised Geneva Score, or clinical gestalt. Two reviewers independently
      extracted data onto standardised forms. A total of 5,622 patients with
      low/intermediate or unlikely PTP were assessed using the VIDAS D-dimer. PE was
      ruled out by a negative D-dimer test in 2,248 (40%, 95% confidence intervals [CI]
      38.7 to 41.3%) of them. The three-month thromboembolic risk in patients left
      untreated on the basis of a low/intermediate or unlikely PTP and a negative D
      dimer test was 3/2,166 (0.14%, 95% CI 0.05 to 0.41%). In conclusion, the
      combination of a negative VIDAS D-dimer result and a non-high PTP effectively and
      safely excludes PE in an important proportion of outpatients with suspected PE.

PMID- 19404541
TI  - Venous thromboembolism and bleeding in a community setting. The Worcester Venous
      Thromboembolism Study.
AB  - Bleeding is the most frequent complication of antithrombotic therapy for venous
      thromboembolism (VTE). However, little attention has been paid to the impact of
      bleeding after VTE in the community setting. The purpose of this investigation
      was to describe the incidence rate of bleeding after VTE, to characterize
      patients most at risk for bleeding, and to assess the impact of bleeding on rates
      of recurrent VTE and all-cause mortality. The medical records of residents of the
      Worcester (MA, USA) metropolitan area diagnosed with ICD-9 codes consistent with
      potential VTE during 1999, 2001, and 2003 were individually validated and
      reviewed by trained data abstracters. Clinical characteristics, acute treatment,
      and outcomes (including VTE recurrence rates, bleeding rates, and mortality) over
      follow-up (up to 3 years maximum) were evaluated. Bleeding occurred in 228 (12%)
      of 1,897 patients with VTE during our follow-up. Of these, 115 (58.8%) had
      evidence of early bleeding occurring within 30 days of VTE diagnosis. Patient
      characteristics associated with bleeding included impaired renal function and
      recent trauma. Other than a history of prior VTE, the occurrence of bleeding was
      the strongest predictor of recurrent VTE (hazard ratio [HR] 2.18; 95% confidence
      interval [CI] 1.54-3.09) and was also a predictor of total mortality (HR 1.97;
      95%CI 1.57-2.47). The occurrence of bleeding following VTE is associated with an
      increased risk of recurrent VTE and mortality. Future study of antithrombotic
      strategies for VTE should be informed by this finding. Advances that result in
      decreased bleeding rates may paradoxically decrease the risk of VTE recurrence.

PMID- 19404543
TI  - In-hospital symptomatic venous thromboembolism and antithrombotic prophylaxis in
      Internal Medicine. Findings from a multicenter, prospective study.
AB  - Hospitalised medical patients are at increased risk of venous thromboembolism
      (VTE), but the incidence of hospitalisation-related VTE in unselected medical
      inpatients has not been extensively studied, and uncertainties remain about the
      optimal use of thromboprophylaxis in this setting. Aims of our prospective,
      observational study were to assess the prevalence of VTE and the incidence of
      symptomatic, hospitalisation-related events in a cohort of consecutive patients
      admitted to 27 Internal Medicine Departments, and to evaluate clinical factors
      associated with the use of thromboprophylaxis. Between March and September 2006,
      a total of 4,846 patients were included in the study. Symptomatic VTE with onset
      of symptoms later than 48 hours after admission ("hospital-acquired" events,
      primary study end-point) occurred in 26 patients (0.55%), while the overall
      prevalence of VTE (including diagnosis prior to or at admission) was 3.65%.
      During hospital stay antithrombotic prophylaxis was administered in 41.6% of
      patients, and in 58.7% of those for whom prophylaxis was recommended according to
      the 2004 Guidelines of the American College of Chest Physicians. The choice of
      administering thromboprophylaxis or not appeared qualitatively adherent to
      indications from randomised clinical trials and international guidelines, and bed
      rest was the strongest determinant of the use of prophylaxis. Data from our real
      world study confirm that VTE is a relevant complication in patients admitted to
      Internal Medicine Departments, and recommended tromboprophylaxis is still under
      used, in particular in some patients groups. Further efforts are needed to better
      define risk profile and to optimise prophylaxis in the heterogeneous setting of
      medical inpatients.

PMID- 19404544
TI  - Effects of microgravity and hypergravity on platelet functions.
AB  - Many serious thrombotic and haemorrhagic diseases or fatalities have been
      documented in human being exposed to microgravity or hypergravity environments,
      such as crewmen in space, roller coaster riders, and aircrew subjected to high-G
      training. Some possible related organs have been examined to explore the
      mechanisms underlying these gravity change-related diseases. However, the role of
      platelets which are the primary players in both thrombosis and haemostasis is
      unknown. Here we show that platelet aggregation induced by ristocetin or collagen
      and platelet adhesion to von Willebrand factor (VWF) were significantly decreased
      after platelets were exposed to simulated microgravity. Conversely, these
      platelet functions were increased after platelets were exposed to hypergravity.
      The tail bleeding time in vivo was significantly shortened in mice exposed to
      high-G force, whereas, was prolonged in hindlimb unloaded mice. Furthermore,
      three of 23 mice died after 15 minutes of -8 Gx stress. Platelet thrombi
      disseminated in the heart ventricle and blood vessels in the brain, lung, and
      heart from the dead mice. Finally, glycoprotein (GP) Ibalpha surface expression
      and its association with the cytoskeleton were significantly decreased in
      platelets exposed to simulated microgravity, and obviously increased in
      hypergravity-exposed platelets. These data indicate that the platelet functions
      are inhibited in microgravity environments, and activated under high-G
      conditions, suggesting a novel mechanism for gravity change-related haemorrhagic
      and thrombotic diseases. This mechanism has important implications for preventing
      and treating gravity change-related diseases, and also suggests that special
      attentions should be paid to human actions under different gravity conditions.

PMID- 19404545
TI  - Influence of platelet count on the expression of platelet collagen receptor
      glycoprotein VI (GPVI) in patients with acute coronary syndrome.
AB  - Platelets play a key role in the development of an acute coronary syndrome (ACS)
      and contribute to cardiovascular events. Platelet collagen receptor glycoprotein
      VI (GPVI) contributes significantly to platelet adhesion and thrombus formation
      in ACS. We consecutively investigated both the platelet count and the platelet
      surface expression of GPVI in 843 patients with a symptomatic coronary artery
      disease verified by coronary angiography. Four hundred fourteen patients
      presented with stable angina pectoris and 429 patients with ACS. Platelet surface
      expression of GPVI and CD62P was determined by flow cytometry and platelet count
      with a coulter counter, plasmatic soluble GPVI was measured by ELISA. Platelet
      GPVI expression in patients with ACS was compared to platelet count. Patients
      with ACS showed significantly elevated GPVI expression levels in the first and
      second quartiles of platelet count compared to patients with higher platelet
      count [mean fluorescence intensity (MFI) +/- standard deviation): 1(st) vs.
      4(th): 20.44 +/- 6.1 vs. 18.62 +/- 3.7; p=0.012; 2(nd)vs.3(rd):21.2+/
      8.5vs.18.76+/-3.7;P=0.03; 2(nd)vs.4(th): 21.2+/-8.5vs.18.62+/-3.7;P=0.004], which
      was paralleled in trend for the CD62P expression [MFI: 1(st) vs. 4(th): 11.2 +/-
      6.8 vs. 12.3 +/- 9; p=0.057; 2(nd) vs. 3(rd): 16.3 +/- 16 vs.12.7 +/- 5.3;
      p=0.138; 2(nd) vs. 4(th): 16.3 +/- 16 vs.11 +/- 4.4; p=0.043]. In a subgroup of
      48 patients with ACS, determination of soluble GPVI showed similar results
      [plasma GPVI (ng/ml): 1(st)vs.4(th): 1.6 +/- 0.6 vs. 1.2 +/- 0.4; p=0.046; 1(st)
      vs. 3(rd): 1.6 +/- 0.6 vs. 1.1 +/- 0.5; p=0.038; 2(nd) vs. 3(rd): 1.9 +/- 0.8 vs.
      1.1 +/- 0.5; p=0.04; 2(nd) vs. 4(th): 1.9 +/- 0.8 vs. 1.2 +/- 0.4; p=0.056].
      Thus, a lower platelet count comes along with a higher GPVI surface expression
      and plasma concentration in patients with ACS, which potentially reflects
      increased activation and enhanced recruitment of platelets to the site of
      vascular injury.

PMID- 19404546
TI  - Modification of the cytoprotective protein C pathway during Dengue virus
      infection of human endothelial vascular cells.
AB  - Dengue fever (DF) is the most prevalent arthropod-borne viral disease of humans.
      No safe vaccine is available, there is no experimental animal model and no
      specific treatment (antiviral) for Dengue virus (DV) infection exists. The
      pathogenic mechanisms of the severe forms of the disease, such as Dengue shock
      syndrome (DSS) and Dengue haemorrhagic fever (DHF), in which endothelial damage
      is the pathognomonic sign, are not fully understood. Clinical observations have
      revealed significant abnormalities in the coagulation and inflammation systems,
      with increased levels of soluble thrombomodulin (sTM) in the plasma of patients
      with DHF/DSS (grade III or IV). Blood sTM was proposed as an early predictor of
      DSS during the febrile stage. However, the role of the DV in endothelial injury
      during DSS is unclear. Here, we present novel insights into the participation of
      DV in the downregulation of the thrombomodulin-thrombin-protein C complex
      formation at the endothelial surface, with a reduction in activated protein C
      (APC). APC is the most important vasoprotective protein because it downregulates
      thrombin generation (by the inactivation of procoagulant factors Va and VIIIa)
      and has anti-inflammatory, antiapoptotic, and barrier protection properties.
      These biological functions of APC are associated with the endothelial protein C
      receptor (EPCR) and protease-activated receptor 1 (PAR-1) signalling pathways,
      which link the coagulation-inflammation responses. We found alterations in the
      antithrombotic and cytoprotective protein C pathways during DV infection of human
      endothelial vascular cells, which may explain the vasculopathy observed during
      DHF/DSS. Clarification of the basic principles that underlie these processes has
      important implications for the design of new therapeutic strategies for DHF/DSS.

PMID- 19404547
TI  - Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with
      other subtypes of ischaemic stroke.
AB  - Few studies have examined the relationship between inflammatory biomarker blood
      levels, cardioembolic stroke subtype and neurological deficit. So the aim of our
      study is to evaluate plasma levels of immuno-inflammatory variables in patients
      with cardio-embolic acute ischaemic stroke compared to other diagnostic subtypes
      and to evaluate the relationship between immuno-inflammatory variables, acute
      neurological deficit and brain infarct volume. One hundred twenty patients with
      acute ischaemic stroke and 123 controls without a diagnosis of acute ischaemic
      stroke were evaluated. The type of acute ischaemic stroke was classified
      according to the TOAST classification. We evaluated plasma levels of IL-1beta,
      TNF-alpha, IL-6 and IL-10, E-selectin, P-selectin, sICAM-1,sVCAM-1, vWF, TPA and
      PAI-1. Patients with ischaemic stroke classified as cardio-embolic (CEI) showed,
      compared to other subtypes, significantly higher median plasma levels of TNF
      alpha , IL-6 and IL-1beta. Furthermore stroke patients classified as lacunar
      showed, compared to other subtypes, significantly lower median plasma levels of
      TNF-alpha, IL-6 and IL-1beta. Multiple linear regression showed a significant
      association between the Scandinavian Stroke Scale (SSS) score at admission and
      diagnostic subtype, infarct volume of cardio-embolic strokes and some
      inflammatory variables. Our findings confirm that cardio-embolic strokes have a
      worse clinical presentation and produce larger and more disabling strokes than
      other ischaemic stroke subtypes reporting a possible explanation of higher immuno
      inflammatory activation of the acute phase.

PMID- 19404548
TI  - Gender differences in stroke risk of atrial fibrillation patients on oral
      anticoagulant treatment.
AB  - The efficacy of adjusted-dose oral anticoagulant treatment (OAT) in the
      prevention of stroke in atrial fibrillation (AF) is well documented. Available
      data show that AF patients are widely heterogeneous in terms of ischaemic stroke
      risk. The role of female gender as a predictor of stroke risk is inconsistent, in
      particular it is unclear if warfarin treatment is able to prevent stroke equally
      in both sexes. We performed a prospective study on 780 AF patients on OAT,
      followed by an Anticoagulation Clinic, to evaluate if female gender is a risk
      factor for stroke among patients on OAT and if the quality of anticoagulation is
      different between genders. No difference was found in relation to the quality of
      anticoagulation between genders (p=0.5). During follow-up 33 patients had major
      bleedings (rate 1.37 x 100 pt/yrs) but no difference was found between genders in
      bleeding risk. Forty patients had ischaemic events [rate 1.66 x 100 pt/yrs; males
      rate 1.2 x 100 pt/yrs; females rate 2.43 x 100 pt/yrs; p=0.042; relative risk
      (RR) of females vs. males 2.0 (95% confidence interval [CI] 1.3-3.1); p= 0.004].
      The higher rate of ischaemic events in females with respect to males was
      confirmed at Cox regression analysis after correction for age (p=0.009). In
      addition, strokes occurring in females were more disabling, and RR for severe and
      fatal stroke, defined according to Modified Rankin scale, of females vs. males
      was 3.1 (95% CI 1.3-6.5; p=0.001). In conclusion, our data show a higher risk of
      stroke in anticoagulated AF females with respect to males, despite a similar
      quality of anticoagulation.

PMID- 19404549
TI  - Variants in the coagulation factor 2 receptor (F2R) gene influence the risk of
      myocardial infarction in men through an interaction with interleukin 6 serum
      levels.
AB  - Thrombin-activated factor 2 receptor (F2R) links thrombosis to inflammation
      modulating interleukin (IL)6 synthesis. We have investigated the role of F2R
      genetic variants and their interaction with IL6 serum levels in the occurrence of
      myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP).
      Seven SNPs -1738 G/A, -506-/GGCCGCGGGAAGC (D/I), 2860 G/A, 2930 T/C, 9113 C/A,
      9333 C/T and 120813 T/C within F2R locus were genotyped in the SHEEP (n=2,774).
      The C allele at position 2930 was associated with a slight reduction in MI risk
      in men. IL6 serum levels were higher in male cases carrying genotypes AA at the 
      1738 (p= 0.01) and GG at the 2860 loci (p= 0.03) and both alleles were found to
      differentially modulate IL6 serum levels in the context of selective haplotypes.
      High IL6 serum levels (>75(th) percentile), were independently associated with an
      increased risk of MI in men with an odds ratio (OR) (95% confidence interval
      [CI]) of 2.44 (1.72-3.46), (p=0.0016), but not in women ( OR 0.83 [95%CI 0.50
      1.36], p=0.64). In the presence of high IL6 serum levels, the -1738A allele
      increased and the 2860A allele reduced the risk of MI (all p < or = 0.02).
      Consistently, the AG diplotype increased MI risk (OR 1.71 [95%CI 1.17-2.51],
      p=0.005). The -1738 and 2860 loci association with IL6 serum levels was
      replicated in men in the Stockholm Coronary Artery Risk Factor (SCARF) study
      (both p < or = 0.04). In the pooled data from the two populations, the A and G
      allele modulated the risk of MI in men with high IL6 serum levels (p < or =
      0.03). Our results demonstrate that in men F2R genetic variants influence the
      risk of MI mainly through an interaction with IL6 serum levels.

PMID- 19404550
TI  - Regulation of urokinase receptor function and pericellular proteolysis by the
      integrin alpha(5)beta(1).
AB  - Interactions between the uPA receptor (uPAR) and various integrins, including
      alpha(5)beta(1), are known to modulate integrin-dependent cell adhesion, and we
      have shown that the integrin-associated tetraspanin protein CD82 down-regulates
      uPAR-dependent plasminogen activation by affecting alpha(5)beta(1) cellular
      localisation. Here we have investigated whether overexpression of alpha(5)beta(1)
      directly affects uPAR-dependent pericellular proteolysis. CHO cells
      overexpressing alpha(5)beta(1) were found to activate plasminogen at a rate up to
      18-fold faster than B2CHO cells which are alpha(5)-deficient. This effect was
      dependent on the activation state of alpha(5)beta(1), as it was maximal in the
      presence of Mn(2+). To determine the role of uPAR-alpha(5)beta(1) interactions in
      this effect, we determined the adhesion of these cells to immobilised soluble
      uPAR (suPAR). Neither cell-type was found to adhere to suPAR, but both cell types
      were found to adhere to an anti-uPAR monoclonal antibody in a uPAR- and integrin
      dependent manner. This adhesion was 10-fold greater in the absence of
      alpha(5)beta(1), possibly implicating the involvement of non-alpha(5)-integrins.
      Soluble forms of the various components were used to investigate the molecular
      basis of these effects, but no direct interactions could be demonstrated between
      alpha(5)beta(1) and either uPAR, uPA or uPA-uPAR complex. This suggests that
      assembly of these components on the plasma membrane is required to influence uPAR
      function, increasing uPAR-dependent pericellular proteolysis and decreasing uPAR
      dependent cell adhesion. These interactions may be modified by other integrins,
      suggesting a complex interplay between uPAR and integrins on the cell surface
      with the potential to regulate invasive cell migration.

PMID- 19404552
TI  - Comparative study of accuracy and clinical agreement of the CoaguChek XS portable
      device versus standard laboratory practice in unexperienced patients.
AB  - The objective of the study was to compare the accuracy and clinical agreement of
      the CoaguChek XS versus the standard laboratory practice. Forty-one patients on
      long-term anticoagulation with acenocumarol without previous experience in self
      monitoring participated to obtain 218 pairs of data. Several methods for
      comparative statistics were applied to assess the possible disagreements between
      techniques as well as a range of previously published criteria of clinical
      agreement and the very recently described error-grid for INR comparison that we
      partially modify. The mean age was 52.1 and the indications for oral
      anticoagulation were prosthetic valves (36.59%), atrial fibrillation (34.15%),
      venous thromboembolic disease (21.95%) and others (7.31%) with a target range of
      2-3 INR units (63.4%) or 2.5-3.5 (36.6%). Analyzing the whole series of data, the
      Pearsons rho correlation coefficient for precision between methods was 0.95 and
      the C(b) bias correction factor for accuracy 0.99 with a minimal bias of 0.1 INR
      units between methods applying the Bland-Altman plot. The linear regression
      procedure described by Passing and Bablok showed a minimal deviation from the
      best-fit line and a slope of 0.90. The mean of the absolute relative differences
      was 7% which is in the "very good" range of agreement. No results were found in
      the clinically "dangerous" D zone of the error-grids with 99% of data in the
      clinically irrelevant and low relevant areas A and B. In this study self
      management with the CoaguChek XS was clinically safe and reliable.

PMID- 19404551
TI  - Association of genetic variants with myocardial infarction in Japanese
      individuals with chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a serious clinical condition that is associated
      with a high incidence of cardiovascular disease and end-stage renal disease.
      Although CKD has been recognised as a risk factor for myocardial infarction (MI),
      genetic factors for predisposition to MI in individuals with CKD have remained
      largely unknown. The purpose of the present study was to identify genetic
      variants that confer susceptibility to MI in Japanese individuals with CKD. The
      study subjects comprised 1,339 Japanese individuals with CKD, including 496
      subjects with MI and 843 controls. The genotypes for 248 polymorphisms of 181
      candidate genes were determined by a method that combines the polymerase chain
      reaction and sequence-specific oligonucleotide probes with suspension array
      technology. An initial screen of allele frequencies by the chi-square test
      revealed that the 11496G-->A (Arg353Gln) polymorphism of F7 (rs6046) was
      significantly (false discovery rate <0.05) associated with the prevalence of MI
      in individuals with CKD. Subsequent multivariable logistic regression analysis
      with adjustment for covariates and a stepwise forward selection procedure also
      revealed that this polymorphism was significantly (p <0.005) associated with MI,
      with the variant A (Gln) allele protecting against this condition. Determination
      of genotype for the 11496G-->A (Arg353Gln) polymorphism of F7 may prove
      informative for assessment of the genetic risk for MI in individuals with CKD.

PMID- 19404553
TI  - Fibrinogen Krakow: a novel hypo/dysfibrinogenemia mutation in fibrinogen gamma
      chain (Asn325Ile) affecting fibrin clot structure and function.

PMID- 19404554
TI  - First case of protein S deficiency due to a translocation t(3;21)(q11.2;q22).

PMID- 19404555
TI  - Two novel mutations at contiguous codons in the fibrinogen Bbeta chain associated
      with hypofibrinogenaemia.

PMID- 19404556
TI  - Endothelial progenitor cells are selectively mobilised immediately after coronary
      artery bypass grafting or valve surgery.

PMID- 19404557
TI  - Competition of unfractionated heparin and idraparinux on activated partial
      thromboplastin time and effect of exogenous antithrombin.

PMID- 19404558
TI  - Evaluation of the CoaguChek XS Plus system in a Swiss community setting.

PMID- 19404559
TI  - N-nitrosamines in the southern Swedish rubber industries - exposure, health
      effects, and immunologic markers.
AB  - OBJECTIVES: The aim of this study was twofold: (i) to evaluate the air levels of
      N-nitrosamines in the Swedish rubber industry and (ii) to estimate the risk of
      symptoms and changed levels of immunologic markers in relation to these levels.
      METHODS: Using adsorption tubes, we collected samples of N-nitrosamines in the
      breathing zone of 96 rubber workers and analyzed them with liquid chromatography
      tandem mass spectrometry. Of these 96 workers, 66 were included in a medical
      examination and blood analysis together with an additional 106 rubber workers and
      118 unexposed subjects. Medical and occupational histories were obtained in
      structured interviews, symptoms were recorded and immunologic markers analyzed in
      blood. RESULTS: The sum of N-nitrosamines ranged from less than the limit of
      detection to 36 microg/m (3)and differed with the vulcanization (ie, curing
      process) method used. Workers vulcanizing with a salt bath had the highest levels
      (median 4.2 microg/m (3)). Compared to the unexposed subjects, the rubber workers
      had an increased risk of nosebleeds, eye and throat symptoms, hoarseness, cough,
      nausea, headache, and changed levels of eosinophils and total immunoglobulin G
      (IgG). However, we found no clear exposure-response relationship with the
      symptoms or the immunologic markers studied. CONCLUSIONS: High levels of N
      nitrosamines were found and must be lowered considerably in order to decrease the
      risk of cancer. There is a need for an occupational exposure limit for N
      nitrosamines in Sweden. The lack of exposure-response relationships with the
      subacute symptoms examined in this study may be due to a healthy-worker selection
      or to the possibility that the symptoms are caused by an exposure not co-varying
      with N-nitrosamines.

PMID- 19404560
TI  - A tumor of an ectopic ureter mimicking uterine cervix adenocarcinoma: case report
      and brief review.
AB  - Single system ectopic ureter is a rare congenital malformation of the urinary
      tract, frequently associated with genital tract malformations. We report the
      first case of an adenocarcinoma arising in an ectopic ureter in a woman and
      mimicking uterine cervical adenocarcinoma. A 34-year-old woman, previously
      diagnosed as having bicornuate uterus, presented with post-coital bleeding. On
      gynecological exam, there were two cervixes with a small nodule on the left
      cervix. After nodule biopsy, the initial diagnosis was adenocarcinoma of the
      uterine cervix. Pelvic ultrasound and magnetic resonance imaging demonstrated an
      ectopic tumoral ureter draining a dysplastic pelvic kidney and inserted in the
      cervix of a bicornuate uterus. The patient was treated by radical hysterectomy
      and left nephroureterectomy. Pathological exam demonstrated an adenocarcinoma
      arising in the ectopic ureter. We suggest that this case could be an argument for
      recommending regular follow-up for women with ectopic ureter for detecting
      malignant transformation.

PMID- 19404561
TI  - The association between diabetes mellitus and urinary incontinence in adult
      women.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of the study was to investigate the
      relationship of diabetes mellitus and urinary incontinence in adult women.
      METHODS: We conducted a cross-sectional, comparative study with a case-control
      design. One thousand three hundred eighty-one women (aged 20-87 years) attending
      six Primary Healthcare Centers in Turkey were enrolled in this study, after
      giving their informed consent. Subjects were dichotomized into cases and controls
      according to presence of diabetes mellitus (DM) and were matched for the
      confounding factors age, body mass index (BMI), and reproductive history.
      RESULTS: Nine hundred ten women were included: 273 diabetics and 637 non
      diabetics. Diabetes was shown to be associated with a 2.5-fold risk increase for
      urinary incontinence (UI), and age and BMI were weakly associated with UI. UI was
      significantly more prevalent in diabetic women: 41% diabetic and 22.1% non
      diabetic women reported UI (p < 0.001). Age, BMI, and DM were revealed as
      independent determinants of UI in adult women. Urge incontinence was more
      prevalent in non-diabetic women, whereas stress and mixed incontinence were more
      prevalent among diabetic women. CONCLUSIONS: DM is the most important independent
      determinant of UI.

PMID- 19404562
TI  - Orally administered lemon/orange juice improved MRCP imaging of pancreatic ducts.
AB  - BACKGROUND: The aim of this study was to determine the effectiveness of oral
      administration of lemon/orange juice in improving the visualization of pancreatic
      ducts on MRCP. MATERIALS AND METHODS: MRCP images were generated before and at
      every 15 min for 90 min after oral administration of lemon/orange juice in a dose
      of 2 ml/kg in 20 volunteers and 26 patients. The pre- and post-administration
      images were compared and analyzed qualitatively and quantitatively. RESULTS: In
      20 volunteers and 26 patients, the visualization at pancreatic duct of head,
      body, tail, accessory pancreatic duct, and branch duct was improved after juice
      administration. The diameter of pancreatic ducts was augmented, and the
      differences in the mean values before and after oral juice were highly
      significant at both sites in volunteers and patients (P < 0.01). In 20 volunteers
      and 26 patients, after juice administration, the best visualization of the
      pancreatic duct was achieved at (58.98 +/- 14.96) min and (59.41 +/- 13.79) min,
      respectively, and the overlap imaging of oral juice was especially observed at
      (42.86 +/- 10.92) min and (41.63 +/- 9.32) min, respectively. CONCLUSIONS: Orally
      lemon/orange juice is an effective method to improve MRCP imaging of pancreatic
      ducts. The lemon/orange juice should be administered at 60 min prior to MRCP.

PMID- 19404563
TI  - Hypocholesterolemic effect of Nostoc commune var. sphaeroides Kutzing, an edible
      blue-green alga.
AB  - BACKGROUND: Intake of an edible blue-green alga Nostoc commune var. sphaeroides
      Kutzing (N. Commune) has been shown to lower plasma total cholesterol
      concentration, but the mechanisms behind the hypocholesterolemic effect have not
      been elucidated. AIM OF THE STUDY: To elucidate the mechanisms underlying the
      cholesterol-lowering effect of N. commune in mice. METHODS: Male C57BL/6J mice
      were fed the AIN-93 M diet supplemented with 0 or 5% (wt/wt) dried N. Commune for
      4 weeks. Lipid levels in the plasma and liver, intestinal cholesterol absorption
      and fecal sterol excretion were measured. Expression of hepatic and intestinal
      genes involved in cholesterol metabolism was evaluated by quantitative realtime
      PCR. RESULTS: N. commune supplementation significantly reduced total plasma
      cholesterol and triglyceride concentrations by approximately 20% compared to
      controls. Intestinal cholesterol absorption was significantly decreased, while
      fecal neutral sterol output was significantly increased in N. commune-fed mice.
      mRNA levels of the cholesterol transporters such as Niemann Pick C1 Like 1,
      scavenger receptor class B type 1, ATP-binding cassette transporters G5 and A1 in
      small intestine were not significantly different between two groups. Hepatic
      lipid contents including total cholesterol, triglyceride and free cholesterol in
      N. commune-fed mice were not significantly altered. However, the expression of
      cholesterol modulating genes including sterol regulatory element binding protein
      2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase were significantly
      increased in mice fed N. commune. CONCLUSIONS: N. commune supplementation exerted
      a hypocholesterolemic effect in mice, largely in part, by reducing intestinal
      cholesterol absorption and promoting fecal neutral sterol excretion.

PMID- 19404565
TI  - Effects of high glucose and thiamine on the balance between matrix
      metalloproteinases and their tissue inhibitors in vascular cells.
AB  - Pericyte survival in diabetic retinopathy depends also on interactions with
      extracellular matrix (ECM) proteins, which are degraded by matrix
      metalloproteinases (MMP). Elevated glucose influences ECM turnover, through
      expression of MMP and their tissue inhibitors, TIMP. We reported on reduced
      pericyte adhesion to high glucose-conditioned ECM and correction by thiamine. We
      aimed at verifying the effects of thiamine and benfotiamine on MMP-2, MMP-9 and
      TIMP expression and activity in human vascular cells with high glucose. In HRP,
      MMP-2 activity, though not expression, increased with high glucose and decreased
      with thiamine and benfotiamine; TIMP-1 expression increased with high glucose
      plus thiamine and benfotiamine; MMP-9 was not expressed. In EC, MMP-9 and MMP-2
      expression and activity increased with high glucose, but thiamine and
      benfotiamine had no effects; TIMP-1 expression was unchanged. Neither glucose nor
      thiamine modified TIMP-2 and TIMP-3 expression. TIMP-1 concentrations did not
      change in either HRP or EC. High glucose imbalances MMP/TIMP regulation, leading
      to increased ECM turnover. Thiamine and benfotiamine correct the increase in MMP
      2 activity due to high glucose in HRP, while increasing TIMP-1.

PMID- 19404564
TI  - Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular
      carcinoma.
AB  - BACKGROUND: Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB
      DTPA) is an MRI contrast agent with perfusion and hepatoselective properties. The
      purpose of the study was to examine uptake of Gd-EOB-DTPA in the hepatobiliary
      phase in hepatocellular carcinoma (HCC). METHODS: A retrospective analysis of 22
      patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI was
      performed. Enhancement ratios (ERs) and expression levels of the organic anion
      transporter (OATP) 1B3 protein were examined. RESULTS: Gd-EOB-DTPA accumulated in
      the hepatobiliary phase in 6 of the 22 cases. All 6 Gd-EOB-DTPA-positive cases
      were moderately differentiated HCC, but 11 other moderately differentiated HCCs
      did not show Gd-EOB-DTPA uptake. Histopathologically, 4 Gd-EOB-DTPA-positive HCCs
      and 5 Gd-EOB-DTPA-negative HCCs produced bile. HCCs with Gd-EOB-DTPA uptake
      overexpressed OATP1B3 compared with HCCs without Gd-EOB-DTPA uptake, and OATP1B3
      levels were significantly correlated with ERs (r=0.91, P<0.0001). CONCLUSIONS:
      Uptake of Gd-EOB-DTPA in HCC is determined by expression of OATP1B3 rather than
      by tumor differentiation or bile production.

PMID- 19404566
TI  - Influence of iron metabolism indices on glycated haemoglobin but not glycated
      albumin levels in premenopausal women.
AB  - We have recently shown that in premenopausal women without anaemia, glycated
      haemoglobin (HbA(1C)) is inversely associated with mean corpuscular haemoglobin
      (MCH). Based on the hypothesis that iron deficient state (IDS) due to
      menstruation may influence erythrocyte metabolism and thereby HbA(1C) levels, we
      examined the relation of iron metabolism indices with HbA(1C) in premenopausal
      women. HbA(1C), serum glycated albumin (GA) and iron metabolism indices were
      determined in 104 premenopausal women with normal glucose tolerance. Among them,
      17 were diagnosed with iron deficiency anaemia (IDA) and 30 with IDS. The other
      57 subjects were diagnosed with normal iron state (NIS). HbA(1C) levels showed
      significant inverse association with serum iron, serum transferrin saturation and
      serum ferritin in 104 study participants. Multivariate regression analysis
      identified serum ferritin as negatively associated with HbA(1C). These were also
      observed in 87 premenopausal women without IDA. HbA(1C) levels in IDA subjects
      and in IDS subjects were higher than it in NIS subjects, while GA levels were not
      different among the three groups of subjects. In conclusions, iron metabolism
      indices influence HbA(1C) levels, but not serum GA levels, in premenopausal
      women.

PMID- 19404567
TI  - How increased VEGF induces glomerular hyperpermeability: a potential signaling
      pathway of Rac1 activation.
AB  - Despite growing evidence for a pathogenic role of vascular endothelial growth
      factor (VEGF) in microvascular complications of diabetes, the underlying
      mechanism responsible for its detrimental effect remains unknown. In the current
      study, we hypothesized that some of the detrimental effects of VEGF on
      microvascular endothelial cells in the diabetic milieu stem from its aberrant
      signaling, which leads to perturbed tight junction assembly and increased
      endothelial permeability. Using an integrated in vitro approach, we investigated
      whether the effect of VEGF on endothelial cell permeability involves Rac1 GTPase
      activation and tight junction disassembly. Rac1 activity was detected by Western
      blotting in cell membrane protein as well as pull-down assay. The permeability of
      glomerular endothelial cells monolayer was detected as transendothelial
      electronic resistance. Then tyrosine phosphorylated occludin protein was detected
      by Western blotting after immunoprecipitation. N17Rac1 cells are obtained by
      transfection of glomerular endothelial cells with a dominant negative mutant of
      Rac1. The data obtained in this study indicate that activation of Rac1 GTPase
      contributes to VEGF-induced endothelial cell hyperpermeability. We also observed
      that Rac1 activation leads to increased endothelial permeability through tyrosine
      phosphorylation of occludin. Indeed, N17Rac1 cells dramatically attenuated the
      effect of VEGF on phospho-occludin and endothelial cell permeability. These
      results, when taken together, provide a framework for understanding the role of
      VEGF-induced Rac1/phospho-occludin pathway in the integrity of endothelial
      barrier function in the glomerulus.

PMID- 19404568
TI  - Analysis of the membrane fluidity of erythrocyte ghosts in diabetic,
      spontaneously hypertensive rats.
AB  - Diabetes and hypertension are closely related diseases associated with changes in
      membrane fluidity. Here, we measured the membrane fluidity of erythrocyte ghosts
      from spontaneously hypertensive rats (SHR), with or without streptozotocin (STZ)
      induced diabetes, at the ages of 1, 3 and 6 months, by introducing the use of the
      intramolecular excimer forming dipyrenylpropane (DPyP) in this model. Type 2
      diabetes mellitus (T2DM) was induced in 48-h-old, newborn male SHR by
      intraperitoneal injection of STZ. We found lower excimer to monomer (I (e)/I (m))
      DPyP ratios in diabetic SHR than in control SHR at 3 and 6 months old, indicating
      a decrease in membrane fluidity. Simultaneously, the composition of fatty acids
      was determined and it was found that the unsaturated to saturated fatty acids
      ratio (U/S) was compatible with changes in membrane fluidity. These results
      suggest that the change in fatty acid composition of erythrocyte ghosts
      contributes significantly to the decreased membrane fluidity detected with DPyP
      in diabetic SHR.

PMID- 19404569
TI  - Atypic geniculate neuralgia: atypic anatomic correlation of cranial nerve roots
      and AICA.
AB  - Geniculate neuralgia is a rare cause of craniofacial pains. The anterior inferior
      cerebellar artery is the offending vessel which compress nervus intermedius in
      the patients with typical geniculate neuralgia. We report a patient whose pain
      was atypical for either geniculate neuralgia and trigeminal neuralgia. At
      operation the anterior inferior cerebellar artery was coursing with the nerves
      and was separated. After the decompression the pain resolved immediately.

PMID- 19404570
TI  - Management strategies of intercavernous sinus bleeding during transsphenoidal
      surgery.
AB  - BACKGROUND: Transsphenoidal surgery has been well established as an effective
      primary treatment for tumours of the sellar region. During the dural opening, the
      prominent intercavernous sinus poses limitations for this approach and may
      contribute to incomplete tumour resections. METHOD: Based on our experience from
      940 cases of conventional transsphenoidal surgery, we have developed a stepwise
      protocol for achieving bleeding control in 72 cases (7.7%) that had prominent
      anterior intercavernous sinus. FINDINGS: A custom-made 45-degree right- or left
      angled bipolar coagulator (38 cases) or Landolt bipolar coagulator (29 cases;
      Aesculp, Tuttlingen, Germany) was inserted into the small dural opening, and both
      of the dural layers were coagulated together so that the potential space between
      the endoosteal layer and meningeal layer could be sealed, and the dural opening
      could be extended. When the anterior portion of the medial wall of the cavernous
      sinus was accidentally opened, we then placed a small piece of oxidised
      regenerated cellulose (Surgicel; Johnson & Johnson, North Yorkshire, UK) at the
      opening of the medial wall of the cavernous sinus and coagulated both dural
      layers together starting from the sellar floor side with a custom-made 45-degree
      angled bipolar coagulator. For the relatively large opening of the cavernous
      sinus, a microfibrillar collagen haemostat (Avitene; MedChem Products, Woburn,
      MA) or fleece-coated fibrin glue (TachoComb; Nycomed Austria, Linz, Austria)
      patch was applied over the opened cavernous sinus with gentle compression and was
      found to be effective in most cases. Rarely, direct suture of the opened medial
      wall of the cavernous sinus was necessary in five cases. CONCLUSIONS: We describe
      a stepwise approach to overcome unusual bleedings from the prominent
      intercavernous sinus during conventional transsphenoidal surgery. Our surgical
      experience reveals that these methods can be very effective for the control of
      sinus bleeding.

PMID- 19404571
TI  - Medial wall of the cavernous sinus: microanatomical diaphanoscopic and episcopic
      investigation.
AB  - PURPOSE: To elucidate the question whether expansion of pituitary adenomas into
      the cavernous sinus (CS) has to be regarded as focal penetration rather than
      invasion, a microanatomical study of the medial wall (MW) of the CS was
      performed. METHOD: Fourteen sellar hemiblocks underwent microsurgical dissection
      from lateral and medial approach. The thickness of the MW of the CS was examined
      by diaphanoscopy. FINDINGS: The internal carotid artery (ICA) was adherent to the
      MW in five cases. In five specimens the lateral wall of the sella turcica
      consisted of a single layer without perforations. In nine cases this wall had two
      layers. There was no perforation of both layers in any case. Diaphanoscopy
      revealed thin MW in the lateral border of the sella (n = 13), below the
      horizontal segment of the ICA (n = 10), and antero-inferiorly to the carotid
      syphon (n = 9). CONCLUSIONS: Expansion into the CS may be facilitated by low
      anatomical resistance against chronic tumor growth.

PMID- 19404572
TI  - Long-term implantation of deep brain stimulation electrodes in the pontine
      micturition centre of the Gottingen minipig.
AB  - AIM: To implant deep brain stimulation (DBS) electrodes in the porcine pontine
      micturition centre (PMC) in order to establish a large animal model of PMC-DBS.
      METHOD: Brain stems from four Gottingen minipigs were sectioned coronally into 40
      mum-thick histological sections and stained with Nissl, auto-metallographic
      myelin stain, tyrosine hydroxylase and corticotrophin-releasing factor
      immunohistochemistry in order to identify the porcine PMC. DBS electrodes were
      then stereotaxically implanted on the right side into the PMC in four Gottingen
      minipigs, and the bladder response to electrical stimulation was evaluated by
      subsequent cystometry performed immediately after the operation and several weeks
      later. FINDINGS: A paired CRF-dense area homologous to the PMC in other species
      was encountered in the rostral pontine tegmentum medial to the locus coeruleus
      and ventral to the floor of the fourth ventricle. Electrical stimulation of the
      CRF-dense area resulted in an increased detrusor pressure followed by visible
      voiding in some instances. The pigs were allowed to survive between 14 and 55
      days, and electrical stimulation resulting in an increased detrusor pressure was
      performed on more than one occasion without affecting consciousness or general
      thriving. None of the pigs developed postoperative infections or died
      prematurely. CONCLUSIONS: DBS electrodes can be implanted for several weeks in
      the identified CRF-dense area resulting in a useful large animal model for basic
      research on micturition and the future clinical use of this treatment modality in
      neurogenic supra-pontine voiding disorders.

PMID- 19404573
TI  - First experimental results with a new waterjet dissector: Erbejet 2.
AB  - BACKGROUND: Waterjet dissection represents a useful technique for many surgical
      procedures. In this experimental study, the technical features and dissection
      qualities of the new Erbejet 2 with its new pump and nozzle applicator system are
      evaluated for its neurosurgical use compared to the established Helix Hydro-Jet.
      METHODS: One hundred twenty-six fresh cadaveric pig brains were simultaneously
      cut with the Helix Hydro-Jet and Erbejet 2. Different pressure levels were
      applied to cerebral tissue with and without meninges, cerebellum and brainstem.
      Additionally, dissection characteristics of various cutting media were
      investigated. FINDINGS: There was a nearly equal dissection quality at up to 10
      bar of both instruments. In contrast to the Helix Hydro-Jet, Erbejet 2
      application at higher pressures resulted in an almost linear increase of
      dissection depth with a small standard deviation. Smoother cutting margins and
      less foaming were found. Preserved vessels were observed with both devices.
      Hydroxyaethyl starch led, in contrast to Ringer's solution and isotonic saline
      solution, to increased dissection width and more foaming. CONCLUSIONS: The new
      Erbejet 2 is more precise, with almost linear correlation of pressure and
      dissection depth compared to the Helix Hydro-Jet. Less foaming and the possible
      application of various separating media are a considerable advantage. All things
      considered, the new Erbejet 2 offers more options to enlarge the field of
      neurosurgical indications for waterjet dissection.

PMID- 19404574
TI  - Intracranial growing teratoma syndrome following radiotherapy--an unusually
      fulminant course.
AB  - INTRODUCTION: Residual radiologically progressive masses following multimodality
      treatment of malignant mixed intracranial germ cell tumors are described. Often
      these enlarge, and this is called the growing teratoma syndrome. A similar
      phenomenon during radiotherapy alone has not been described. SUBJECTS AND
      METHODS: A 5-year old boy presented with features of raised intracranial
      pressure. Imaging revealed a posterior third ventricular mass, which was biopsied
      endoscopically. RESULTS: A review of the scanty tissue was suggestive of a pineal
      parenchymal tumor, and hence radiation was planned. After just ten fractions, he
      developed rapid neurological deterioration. Repeat imaging raised a possibility
      of a teratomatous tumor. He underwent emergency excision. However, he had a
      stormy postoperative course and succumbed to deep venous infarction. Histology
      revealed a purely mature teratoma. CONCLUSION: Though a growing teratoma syndrome
      has been described following chemotherapy, no such report while on radiation
      exists. Ours could be the first such reported case. We discuss the possible
      mechanisms with a review of the literature.

PMID- 19404575
TI  - Denuded human amniotic membrane seeding bone marrow stromal cells as an effective
      composite matrix stimulates axonal outgrowth of rat neural cortical cells in
      vitro.
AB  - BACKGROUND: Previous studies have shown that axonal outgrowth in the damaged
      central nervous system is closely related to the local microenvironment.
      Transplantation of bone marrow stromal cells (BMSC) or BMSC with some
      biomaterials has been used to treat various central nervous system diseases with
      some success. In the current study, we investigated if BMSC on denuded human
      amniotic membrane (DhAM) as a composite matrix could stimulate axonal outgrowth
      or not. METHOD: After completely removing the cells on the amniotic membrane with
      a tryptic and mechanical approach, we seeded BMSC on it. The MTS was applied to
      test the cytotoxicity of DhAM compared with PLGA and PLL. The morphology of the
      BMSC was observed by light, electronic and laser confocal microscopy. We also
      used four kinds of substance (PLL, DhAM, BMSC + PLL, BMSC + DhAM) to coculturing
      with the cortical neurons. Finally, the lengths of axons in each group were
      studied using the positive axon-specific marker NF-H. FINDINGS: The DhAM was
      devoid of cellular components and only its intact basement membrane was left.
      BMSC grew on the substrate and proliferated with a flat to fusiform morphology.
      In the MTS test, the results indicated that BMSC cultured in DhAM extract had a
      high survival rate (> 80%). Moreover, the cortical neural axons in the
      experimental group (BMSC + DhAM) were longer (287.37 +/- 12.72 microm) than in
      the other groups (P < 0.01). CONCLUSIONS: This study demonstrates that the DhAM
      was a good carrier to support growth of BMSC and BMSC on DhAM was an effective
      composite matrix to support the outgrowth of the axons of rat cortical neurons in
      vitro. Future studies of the use of the composite matrix in disorders are
      planned.

PMID- 19404576
TI  - Sources and patterns of pain in lumbar disc disease: revisiting Francis Murphey's
      theory.
AB  - OBJECT: Francis Murphey's theory was analyzed to determine whether or not his
      opinion is evidence-based medicine and whether or not it can be applied
      clinically. METHODS: The English literature was reviewed using Medline in
      reference to Dr. Murphey's theory of discogenic chronic LBP, which was first
      postulated in 1967. Deductive and inductive logic was utilized for the evaluation
      of his theory. We reviewed and analyzed his unprecedented study of the annulus
      fibrosus (AF) and posterior longitudinal ligament (PLL) under local anesthesia
      that was presented to the Congress of Neurological Surgeons in 1967 and 1972.
      RESULTS: He reported that: "It is found that the posterior longitudinal ligament
      and the remaining annulus fibrosus over the herniated discs are also exquisitely
      tender; even the slightest pressure on them produces pain." We noticed that in
      Dr. Murphey's presentation, he did not disclose any hard data, yet he concluded:
      "when an incomplete tear in the annulus occurs and if the tear is in the midline
      posterior, a fragment of nucleus will protrude in this tear, stretching the
      annulus and posterior longitudinal ligament, causing midline back pain. If the
      tear in the annulus is lateral, the pain is over the sacroiliac joint in the
      buttock and hip, and 20% of the patients in the lower abdomen, groin or testicle
      on that side." CONCLUSIONS: Because of a flaw in his understanding, in our
      opinion the unproven mechanical theory of discogenic LBP is weak inductive logic
      and does not justify discography and intra-discal procedures.

PMID- 19404577
TI  - Central nervous system cryptococcoma in immunocompetent patients: a short review
      illustrated by a new case.
AB  - OBJECTIVE: Cryptococcal infection in CNS is frequently seen in HIV patients and
      those with other immunosuppressed conditions. However, cryptococcal granuloma in
      CNS in immunocompetent patient is rare. We present one new case of cryptococcoma
      and review literature to illustrate diagnosis and treatment of these lesions.
      METHODS: We conducted literature search in Pubmed search engine of the National
      Center for Biotechnology Information. RESULTS: Seventeen cases of CNS cryptoccoma
      in immunocompetent patients, including ours, have been reported to date. Of them,
      two patients had lesions inside spinal cord, and C. neoformans var. gattii was
      identified in three cases. All patients were symptomatic with normal
      immunocompetency although two patients had type 2 diabetes mellitus and one had
      torsades de pointes. Eight patients received surgical treatment and all were
      given antifungal agents except one suspected of teniasis. CONCLUSIONS: With
      literature reports and our experiences, we suggest that ring shaped enhancement
      of mass lesion with or without cystic changes in MR scan may indicate
      cryptococcoma, but definitive diagnosis relies on pathology study of lesion
      specimen. Open surgery and anti-fungal therapy should be scheduled, and outcome
      of cryptococcoma is largely determined by its locations.

PMID- 19404578
TI  - Reducible and irreducible os odontoideum in childhood treated with posterior
      wiring, instrumentation and fusion. Past or present?
AB  - BACKGROUND: The aim of the study was to evaluate the results of instrumented rod
      and wire fusion in children with craniovertebral junction (CVJ) instability and
      os odontoideum. METHODS: We evaluated seven children (mean age 9.85 years) with
      Down and Morquio's syndromes and primary os odontoideum. X-ray, computerized
      tomography (CT) scan and magnetic resonance (MR) imaging of the CVJ showed
      reducible instability in all of the cases but one. All the children underwent
      surgical correction by means of posterior wiring, instrumentation, fusion and
      external orthosis. A posterior wiring technique was also utilized in the only
      child with irreducible preoperative atlantoaxial instability, which, however,
      proved to be reducible under general anesthesia. FINDINGS: At maximum follow-up
      (observation range 28 to 106 months, mean 59.42 months), the clinical picture was
      improved in all the patients. The postoperative neuroradiological investigations
      demonstrated satisfactory bony fusion with neural decompression in all patients.
      CONCLUSIONS: A wiring technique to correct atlantoaxial instabilities has been
      shown to be more relevant in these children with syndromic atlantoaxial
      dislocation and os odontoideum due to its simplicity, safety (continuous
      fluoroscopic assistance is not necessary and there is no risk of neuro-vascular
      injuries) and lower costs (no complex hardware devices; no neuronavigation
      systems are required). Preoperative irreducibility of the C1-C2 shift is not an
      absolute criterion for transoral decompression in children since os odontoideum
      can be reduced under general anesthesia.

PMID- 19404580
TI  - Promoting Global Research Excellence in Severe Sepsis (PROGRESS): lessons from an
      international sepsis registry.
AB  - BACKGROUND: The PROGRESS Registry (Promoting Global Research Excellence in Severe
      Sepsis) was designed to provide comparative data reflecting everyday clinical
      practice, thereby allowing participating institutions to explore and benchmark
      medical interventions in severe sepsis. MATERIALS AND METHODS: PROGRESS was an
      international, noninterventional, prospective, observational registry collecting
      data that describe the management and outcomes of severe sepsis patients in
      intensive care units (ICUs). Patients were enrolled who had been diagnosed with
      severe sepsis (suspected or proven infection and >or= 1 acute sepsis-induced
      organ dysfunction) at the participating institutions, where de-identified data
      were entered directly into a secured website. PROGRESS was governed by an
      independent international medical advisory board. RESULTS: PROGRESS took place in
      276 ICUs in 37 countries, and 12,881 patients were identified as having severe
      sepsis. There was considerable variation among countries in enrollment levels,
      provision of standard treatment and supportive therapies, and ICU and hospital
      outcomes. Eight countries accounted for 65.2% of the enrolled patients. Males
      (59.3%) and Caucasian (48.6%) patients predominated the patient cohort. Diagnosis
      of severe sepsis was prior to ICU admission in 45.7% of patients, at ICU
      admission in 29.1% of patients, and after ICU admission in the remainder.
      Globally, ICU and hospital mortality rates were 39.2% and 49.6%, respectively.
      The mean length of ICU and hospital stay was 14.6 days and 28.2 days,
      respectively. CONCLUSIONS: The PROGRESS international sepsis registry
      demonstrates that a large web-based sepsis registry is feasible. Wide variations
      in outcomes and use of sepsis therapies were observed between countries. These
      results also suggest that additional opportunities exist across countries to
      improve severe sepsis outcomes.

PMID- 19404582
TI  - Dose-finding and pharmacokinetic study of orally administered indibulin (D-24851)
      to patients with advanced solid tumors.
AB  - Indibulin (ZIO-301/D-24851) is an orally applied small molecule with antitumor
      activity based upon destabilization of microtubule polymerization. The purpose of
      this phase I study was to determine the maximum tolerated dose (MTD) as well as
      the dose limiting toxicity (DLT), the pharmacokinetics, safety and tolerability
      of orally administered indibulin as capsule formulation in patients with advanced
      solid tumors. Patients received a single dose of indibulin. Seven dose-levels
      were evaluated: 100 mg, 150 mg, 250 mg, 350 mg and 600 mg once daily (QD), 450 mg
      and 600 mg twice daily (BID). After a washout period, patients received indibulin
      at the pre-defined daily dose for 14 days every 3 weeks (multiple dose part). A
      total of 28 patients entered the study. Indibulin administered as capsules was
      generally well tolerated. The MTD was not reached. There was a disproportionate
      increase of the area under the plasma concentration-time curve (AUC) with dose,
      with declining AUC corrected for dose starting at the 250 mg dose-level. There
      was no significant difference in AUC of indibulin after multiple dosing (day 1
      14) compared to single administration (day-4). Inter-patient variability in AUC
      (102% CV) was high. A plateau in drug exposure was observed prior to reaching the
      MTD. Continued dose-escalation was unlikely to yield any increase in exposure of
      indibulin. The formulation needs optimization to increase the systemic exposure
      upon oral administration.

PMID- 19404581
TI  - Lipopolysaccharide from Escherichia coli prevents indomethacin-induced gastric
      damage in rats: role of non-protein sulfhydryl groups and leukocyte adherence.
AB  - OBJECTIVE AND DESIGN: To investigate the role of non-protein sulfhydryl groups
      (NP-SH) and leukocyte adhesion in the protective effect of lipopolysaccharide
      (LPS) from Escherichia coli against indomethacin-induced gastropathy. MATERIALS
      OR SUBJECTS: Male Wistar rats were divided into four groups: saline, LPS, saline
      + indomethacin and LPS + indomethacin, with six rats in each group. TREATMENT:
      Rats were pretreated with LPS (300 microg/kg, by intravenous) or saline. After 6
      h, indomethacin was administered (20 mg/kg, by gavage). METHODS: Three hours
      after treatments, rats were killed. Macroscopic gastric damage, gastric NP-SH
      concentration, myeloperoxidase (MPO) activity and mesenteric leukocyte adhesion
      (intravital microscopy) were assessed. Statistical analysis was performed using
      one-way analysis of variance followed by the Newman-Keuls test. Statistical
      significance was set at P < 0.05. RESULTS: LPS reduced the gastric damage,
      gastric MPO activity and increased gastric NP-SH concentration in indomethacin
      induced gastropathy. LPS alone increased gastric NP-SH when compared to saline.
      Indomethacin increased leukocyte adhesion when compared to the saline, and LPS
      reduced indomethacin-induced leukocyte adhesion. In addition, LPS alone did not
      change leukocyte adhesion, when compared to the saline. CONCLUSION: LPS
      protective effect against indomethacin-induced gastropathy is mediated by an
      increase in the NP-SH and a decrease in leukocyte-endothelial adhesion.

PMID- 19404583
TI  - Papillary glioneuronal tumor-evidence of stem cell origin with biphenotypic
      differentiation.
AB  - Papillary glioneuronal tumors are newly recognized seizure producing tumors. We
      report two such cases with immunohistochemical characterization of glial and
      neuronal components and briefly review literature. Co-localization of glial and
      neuronal markers was demonstrable on confocal microscopy with expression of stem
      cell markers (Nestin and CD133) suggesting possible origin from neuroepithelial
      stem cell with biphenotypic differentiation.

PMID- 19404585
TI  - [New agents for the prevention of venous thromboembolism].

PMID- 19404586
TI  - [Fever of unknown origin in malignancies].
AB  - Fever is a common symptom in patients with malignancies. On the one hand it may
      be an (initial) symptom of cancer, on the other hand it may occur as a side
      effect of chemotherapy. Often a precise cause of fever can not be established and
      in these cases febrile temperatures >38.3 degrees C without proof of infection or
      relapse/progress of tumor is defined as fever of unknown origin. Especially
      hematologic neoplasias are accompanied by fever. Here, neoplastic fever must be
      distinguished from fever following immunosuppressive chemotherapy. In the latter
      severe infections due to neutropenia induced by cytoreductive chemotherapy is
      often identified as the cause of fever. These patients display a high morbidity
      and mortality, especially if an empiric anti-infectious treatment is not
      administered in time. A meticulous diagnostic work-up is therefore necessary, and
      until proven otherwise, an infectious cause must be considered and empiric
      antibiotic treatment initiated.

PMID- 19404587
TI  - Combined antiviral activity of interferon-alpha and RNA interference directed
      against hepatitis C without affecting vector delivery and gene silencing.
AB  - The current standard interferon-alpha (IFN-alpha)-based therapy for chronic
      hepatitis C virus (HCV) infection is only effective in approximately half of the
      patients, prompting the need for alternative treatments. RNA interference (RNAi)
      represents novel approach to combat HCV by sequence-specific targeting of viral
      or host factors involved in infection. Monotherapy of RNAi, however, may lead to
      therapeutic resistance by mutational escape of the virus. Here, we proposed that
      combining lentiviral vector-mediated RNAi and IFN-alpha could be more effective
      and avoid therapeutic resistance. In this study, we found that IFN-alpha
      treatment did not interfere with RNAi-mediated gene silencing. RNAi and IFN-alpha
      act independently on HCV replication showing combined antiviral activity when
      used simultaneously or sequentially. Transduction of mouse hepatocytes in vivo
      and in vitro was not effected by IFN-alpha treatment. In conclusion, RNAi and IFN
      alpha can be effectively combined without cross-interference and may represent a
      promising combinational strategy for the treatment of hepatitis C.

PMID- 19404588
TI  - Clinical value of fibrillatory wave amplitude on surface ECG in patients with
      persistent atrial fibrillation.
AB  - PURPOSE: We postulated that amplitude of fibrillatory (F)-wave in patients with
      persistent AF would correlate with clinical characteristics and outcome in
      patients undergoing catheter ablation for AF. METHOD: Maximal and mean amplitude
      of F-waves were measured in V1 and lead II in 90 patients prior to ablation for
      persistent AF. F-wave amplitudes were correlated to clinical, echocardiographic
      variables, and outcome. RESULTS: F-wave > or = 0.1 mV in lead II and V1 was
      correlated with younger age and shorter AF history, and in lead II only was
      correlated with a smaller left atrium. Higher F-wave amplitude at baseline
      predicted AF termination during ablation. Maximal amplitude of > or = 0.07 mV
      predicted AF termination by ablation with 82%/79% sensitivity and 68%/73%
      specificity in V1/lead II respectively. An association between F-wave amplitude
      and AF recurrence was observed. Forty-three percent of patients with mean f wave
      amplitude <0.05 in lead V1 had AF recurrence compared to 12% of those with F-wave
      > or = 0.05 (p = 0.004). CONCLUSION: Longer AF duration, older age and larger LA
      size are associated with fine AF amplitude. High F-wave amplitude predicts
      procedural termination of arrhyhmia in patients with persistent AF and freedom
      from AF upon follow-up.

PMID- 19404589
TI  - The expression of inducible nitric oxide synthase (iNOS) in the testis and
      epididymis of rats with a dihydrotestosterone (DHT) deficiency.
AB  - In our previous studies, we showed that a finasteride-induced DHT deficiency may
      cause changes in the morphology of the seminiferous epithelium without any
      morphological alteration of the epididymis. In this study, we demonstrated the
      constitutive immunoexpression of inducible nitric oxide synthase (iNOS) in the
      testis and epididymis of Wistar rats treated with finasteride for 28 days (the
      duration of two cycles of the seminiferous epithelium) and 56 days (the duration
      of one spermatogenesis). We noted that a 56-day finasteride treatment mainly
      caused a decrease in the level of circulating DHT, as well as a statistically
      insignificant decrease in the level of T. The hormone deficiency also led to a
      change in the iNOS immnoexpression in the testis and epididymis of the
      finasteride-treated rats. In vitro, DHT did not modify NO production by the
      epithelial cells of the caput epididymis even when stimulated with LPS and
      IFNgamma, but it did give rise to an increase in NO production by the epithelial
      cells of the cauda epididymis without the stimulation. DHT did not have a
      statistically significant influence on estradiol production by cultured, LPS- and
      IFNgamma-stimulated epithelial cells from the caput and cauda epididymis. In
      conclusion, our data clearly indicates that a finasterideinduced DHT deficiency
      intensifies the constitutive expression of iNOS in most rat testicular and
      epididymal cells, so it can be expected that the expression of inducible nitric
      oxide synthase (iNOS) could be regulated by DHT. On the other hand, the profile
      of the circulating DHT and T levels strongly suggests that the regulation of
      constitutive iNOS expression is complex and needs more detailed study.

PMID- 19404590
TI  - Effects of gestational cadmium exposure on pregnancy outcome and development in
      the offspring at age 4.5 years.
AB  - The objective of the present study was to evaluate the potential effect of
      maternal cadmium exposure on pregnancy outcome and development in the offspring
      at age 4.5 years. Between November 2002 and December 2003, 109 normal pregnant
      women were enrolled in our cohort from Da-Ye Country, Hubei Province in Central
      China. The placental, whole blood, and cord blood levels of cadmium were
      determined by inductively coupled plasma mass spectrometer (ICP-MS). The 106
      children at 4.5 years of age given birth by the aforementioned women were
      followed up and the following rate was 97.25%. Detailed questionnaire surveys,
      anthropometric measurements were performed, and IQ development was evaluated by
      Wechsler Preschool and Primary Scale of Intelligence Revised Edition (WPPSI-R).
      Multiple linear regression analysis indicated that cord blood cadmium level was
      significantly negatively correlated with fetus development. Low birth weight
      (less than 2,500 g) occurred significantly more frequently in infants with higher
      cord blood cadmium than in those exposed to lower levels of cord blood cadmium.
      Significantly negative correlation was found between cord blood cadmium exposure
      and WPPSI-R IQ full score after controlling for confounding variables. It was
      concluded that cord blood cadmium concentration was a factor that influenced
      fetus growth and later IQ development.

PMID- 19404591
TI  - Aluminium, cadmium and lead concentration in the hair of tobacco smokers.
AB  - In the research, the contents of heavy metals, Al, Cd and Pb, in the hair of
      individuals who reside in similar environmental conditions were spectrometrically
      determined with the use of atomic emission spectrometry-inductively coupled
      plasma spectrophotometer. The relation to their tobacco smoking habit, age and
      sex was established. It was observed that the level of all three determined
      elements was generally higher in the hair of smokers in comparison to hair of non
      smokers in both younger and older age groups. In addition, it has been observed
      that, in the group of elderly people over 50 years old, there was an increase in
      the content of aluminium, cadmium and lead both in smokers and non-smokers,
      irrespective of their sex. The sex-related differences in the content of the
      investigated elements were not unidirectional, and only in few cases did they
      reveal statistical significance.

PMID- 19404595
TI  - [Cost control in treatment of the severely injured by the Trauma Network DGU].

PMID- 19404596
TI  - [Atypical dislocated dens fracture type II with rotational atlantoaxial luxation
      after a riding accident].
AB  - We present a rare case of a combined dislocated odontoid dens fracture type II
      (Anderson/D'Alonzo) and rotational atlantoaxial luxation in a 15-year-old girl
      who was involved in a riding accident.She fell off her horse after it had stopped
      suddenly, losing consciousness for a few minutes. At presentation in the
      hospital, she had no complaints other than limited, painful neck movement.
      Radiologically, a posterior dislocation of an odontoid type II fracture
      (Anderson/D'Alonzo) was found. Computed tomography reconstruction demonstrated a
      rotational, hooklike fixed luxation of the left atlantoaxial facet joint. Manual
      repositioning after application of a cervical collar failed. Therefore, operative
      treatment was indicated for this highly unstable fracture. Posterior
      transarticular atlantoaxial screw fixation according to Magerl was performed; an
      iliac corticocancellous bone graft was harvested and shaped to conform to the
      posterior processes of C1 and C2. Additionally a hook-claw atlas fixation of C1
      was done.To our knowledge, this is the first case of adolescent atlantoaxial
      cervical spine trauma in combination with an odontoid fracture and fixed
      rotational luxation reported in literature.

PMID- 19404597
TI  - [Partial aplasia of the atlas in a child].
AB  - Congenital anomalies of the atlas are rare but well documented. They can range
      from total agenesis to partial clefts of the posterior and/or anterior arches and
      are mostly incidental findings after a sustained trauma. It is essential to
      differentiate these congenital variants from fractures of the atlas to prevent
      the patient from unnecessary (neuro-) surgical intervention. In this article the
      case of a 10-year-old girl is described with an unusual finding of partial
      aplasia of the posterior arch. The clinical features and diagnostic and
      therapeutic procedures are discussed.

PMID- 19404598
TI  - Irresistible bouquet of death--how are burying beetles (Coleoptera: Silphidae:
      Nicrophorus) attracted by carcasses.
AB  - Chemical composition of volatiles emitted from fresh mouse carcasses (laboratory
      mice, Mus musculus) was studied using solid sample injection technique (solid
      phase micro-extraction), two-dimensional gas chromatography with time of flight
      mass spectrometric detection and gas chromatography with electroantennographic
      detection. Electroantennography (EAG) and laboratory olfactometric behavioural
      observations were used to study the antennal sensitivity to identified
      infochemicals and their attractiveness for burying beetles Nicrophorus vespillo
      and Nicrophorus vespilloides (Silphidae: Nicrophorinae). Chemical analysis showed
      that immediately after death, emitted volatiles did not differ from those emitted
      by a living organism. However, in the course of time, sulphur-containing
      chemicals, specifically methanethiol, methyl thiolacetate, dimethyl sulphide,
      dimethyl disulphide and dimethyl trisulphide appear. EAG measurements revealed
      antennal sensitivity to these compounds. Behavioural tests in laboratory
      olfactometer showed that dimethyl sulphide, dimethyl disulphide and dimethyl
      trisulphide are highly attractive to both studied species. The data suggest that
      sulphur-containing chemicals are involved in mediating the fresh carcass
      attractiveness for N. vespillo and N. vespilloides.

PMID- 19404599
TI  - When signal meets noise: immunity of the frog ear to interference.
AB  - Sound stimulates the tympanic membrane (TM) of anuran amphibians through
      multiple, poorly understood pathways. It is conceivable that interactions between
      the internal and external inputs to the TM contribute to the nonlinear effects
      that noise is known to produce at higher levels of the auditory pathway. To
      explore this issue, we conducted measurements of TM vibration in response to
      tones in the presence of noise in the frog Eupsophus calcaratus. Laser vibrometry
      revealed that the power spectra (n = 16) of the TM velocity in response to pure
      tones at a constant level of 80 dB sound-pressure level (SPL) had a maximum
      centered at an average frequency of 2,344 Hz (range 1,700-2,990 Hz) and a maximum
      velocity of 61.1 dB re 1 microm/s (range 42.9-66.6 dB re 1 microm/s). These TM
      vibration velocity response profiles in the presence of increasing levels of 4
      kHz band-pass noise were unaltered up to noise levels of 90 dB SPL. For the
      relatively low spectral densities of the noise used, the TM remains in its linear
      range. Such vibration patterns facilitate the detection of tonal signals in noise
      at the tympanic membrane and may underlie the remarkable vocal responsiveness
      maintained by males of E. calcaratus under noise interference.

PMID- 19404601
TI  - [Report from NeuroUpdate in Wiesbaden (13/14 February 2009)].

PMID- 19404600
TI  - Impact of biocide treatments on the bacterial communities of the Lascaux Cave.
AB  - The Lascaux Cave contains a remarkable set of paintings from the Upper
      Palaeolithic. Shortly after discovery in 1940, the cave was modified for public
      viewing and, in 2001, was invaded by a Fusarium solani species complex.
      Benzalkonium chloride was used from 2001 to 2004 to eliminate the fungal
      outbreak. In this study, we carried out a sampling in most of the cave halls and
      galleries. Sequence analysis and isolation methods detected that the most
      abundant genera of bacteria were Ralstonia and Pseudomonas. We suggest that, as a
      result of years of benzalkonium chloride treatments, the indigenous microbial
      community has been replaced by microbial populations selected by biocide
      application.

PMID- 19404602
TI  - [Internet therapy. Opportunities and boundaries].
AB  - Internet therapy is directed toward people whose access to the usual treatment
      structures is limited. Further, Internet therapy is aimed at patients with
      circumscribed psychiatric disorders or symptoms. Compared to usual face-to-face
      treatment the duration of the Internet therapy programs evaluated were rather
      short, and frequently only small populations were examined. The studies presented
      demonstrate that Internet-based therapy of specific disorders is suitable for a
      significant reduction of symptoms. As follow-up data of longer duration are not
      available, no concluding statement relating to sustained symptom reduction can be
      made. Further, it remains unclear whether efficacy of the Internet therapy
      programs examined is comparable to usual treatment, since only two studies
      compare Internet therapy with face-to-face treatment.

PMID- 19404604
TI  - [Neurosurgical standards in deep brain stimulation : consensus recommendations of
      the German Deep Brain Stimulation Association].
AB  - Surgery combining stereotactically guided implantation of brain electrodes in
      subcortical key structures of the brain with the connection of these brain
      electrodes to subcutaneously implanted impulse generators is one precondition for
      the therapeutic application of deep brain stimulation (DBS). During the last 10
      15 years minimal requirements concerning this surgery have been formulated,
      addressing in particular technical equipment and operational procedures and being
      also in parts supported quantitatively by systematic investigations. Only
      appropriate patient management, high technical standards and an adequate surgical
      technique can minimize the frequency of those complications, which are supposed
      to be directly caused by surgery. High-resolution imaging is the basis for target
      definition, determination of the surgical approach, documentation of final
      electrode position and postoperative exclusion of iatrogenic intracerebral
      haemorrhage. In addition, the quality of treatment planning depends largely on
      the image processing and viewing possibilities provided by specific planning
      software. Further issues, for which standards are defined, address
      electrophysiological and clinical examinations to be performed intraoperatively
      and general surgical measures, which should be considered during implantation of
      DBS systems. This review summarizes and evaluates requirements imposed on the
      aforementioned system components and working steps, taking into consideration
      data from the literature.

PMID- 19404603
TI  - [Deep brain stimulation for essential tremor. Consensus recommendations of the
      German Deep Brain Stimulation Association].
AB  - In Germany, deep brain stimulation (DBS) of the thalamic ventralis intermedius
      nucleus (VIM) is licensed for treatment of essential tremor in cases unresponsive
      to pharmacotherapy. Especially a bothersome hand tremor interfering with
      activities of daily living will improve, whereas head, tongue or vocal tremor
      shows less response. DBS was proven to be superior to lesional thalamotomy with
      better functional outcome and less adverse effects. The consensus statement
      presented here reflects the current recommendations of the German Deep Brain
      Stimulation Study Group for inclusion and exclusion criteria as well as for peri
      , intra- and postoperative neurological management.

PMID- 19404605
TI  - [Deep brain stimulation for dystonia. Consensus recommendations of the German
      Deep Brain Stimulation Association].
AB  - Medical treatment of dystonia, particularly generalised forms of the disorder, is
      often not satisfactory or causes intolerable side effects. In focal dystonia, a
      reasonable treatment option with botulinum toxin exists but some patients either
      do not respond well or develop neutralising antibodies with secondary therapy
      failure. Deep brain stimulation (DBS) of the globus pallidus internus has been
      shown to be effective in both generalised and focal dystonia. This paper gives
      recommendations regarding the use of DBS in different forms of dystonia based on
      the currently available scientific data as well as the longstanding personal
      experience of the authors. The inclusion criteria for DBS candidates as well as
      the peri- and postoperative patient management are addressed. These
      recommendations were developed in a consensus procedure in the German Deep Brain
      Stimulation Association.

PMID- 19404606
TI  - [Affective disorders. The significance of psychotherapeutic approaches].
AB  - The use of psychotherapeutic strategies is essential in the treatment of
      affective disorders. Psychotherapy proved to be at least equivalent to
      antidepressant medication in the treatment of mild to moderate depression. In
      severe cases, the combination of both treatments is considered by guidelines to
      be the standard treatment. Psychotherapeutic approaches show a longer latency
      than antidepressants; however, the effects are longer lasting. Regarding the
      effectiveness of pharmacotherapy sobering results have been published recently.
      Therefore, the further development of psychotherapy deserves special attention.
      Cognitive behavioral therapy and interpersonal therapy provide the highest
      evidence. The empirical basis for psychodynamic psychotherapies is still limited.
      In the treatment of chronic depression a new approach--cognitive behavioral
      analysis system of psychotherapy--is gaining importance. There is a trend towards
      an increasing specification of psychotherapy for distinct subgroups of depressed
      patients. Challenges for the future include increasing treatment efficacy,
      investigating mechanisms of efficacy and predictors for a differential
      indication, and making effective approaches generally available to all patients.

PMID- 19404608
TI  - GAD65 vaccination: 5 years of follow-up in a randomised dose-escalating study in
      adult-onset autoimmune diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this study was to ascertain whether treatment of
      GAD65 autoantibody (GADA)-positive diabetic patients with alum-formulated
      recombinant GAD65 (GAD-alum) is safe and does not compromise beta cell function.
      METHODS: This Phase 2, placebo-controlled, dose-escalation clinical trial, which
      was randomized through a central office, was performed in 47 GADA-positive type 2
      diabetic patients, who received subcutaneous injections of GAD-alum (4 [n = 9],
      20 [n = 8], 100 [n = 9] or 500 [n = 8] microg) or placebo (n = 13) at weeks 1 and
      4 of the trial. Participants and caregivers were blinded to group assignments.
      The primary outcome was safety as assessed by neurological tests, medications and
      beta cell function evaluated over 5 years, representing the end of the trial.
      RESULTS: No severe study-related adverse events occurred during the 5 year follow
      up. None of the dose groups was associated with an increased risk of starting
      insulin treatment compared with the placebo group. The use of oral hypoglycaemic
      agents did not differ between the dose groups. After 5 years, fasting C-peptide
      levels declined in the placebo group (-0.24; 95% CI -0.41 to -0.07 log(10)
      nmol/l; p = 0.01) and the 500 microg dose group (-0.37; 95% CI -0.57 to -0.17
      log(10) nmol/l; p = 0.003), but not in the 4 microg (-0.10; 95% CI -0.28 to 0.07
      log(10) nmol/l; p = 0.20), 20 microg (0.04; 95% CI -0.12 to 0.19 log(10) nmol/l;
      p = 0.58) and 100 microg (0.00; 95% CI -0.20 to -0.20 log(10) nmol/l; p = 0.98)
      dose groups. CONCLUSIONS/INTERPRETATION: The primary outcome of safety was
      achieved, since no severe study-related adverse events occurred. TRIAL
      REGISTRATION: Because the study was initiated before 1 July 2005, the protocol
      was not registered in a registry.

PMID- 19404610
TI  - Early organ dysfunction course, cooling time and outcome in classic heatstroke.
AB  - PURPOSE: To describe the course of early organ dysfunction in a cohort of
      patients admitted in ICU suffering classic heatstroke. METHODS: Prospective
      observational single-centre cohort study with a 1-year follow-up. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Clinical and biological data of 22 patients
      were analysed. Median body temperature on admission was 41.1 degrees C.
      Respiratory, circulatory, haematological, hepatic and renal function all
      deteriorated within the first 24 h of admission. ICU-mortality was 63.6%. Cooling
      time, serum lactate, serum cardiac troponin I and creatinine were significantly
      higher in non-survivors. Early ICU-mortality (within 7 days of ICU stay) was due
      to multiple organ failure. Late ICU-mortality was due to neurological disability.
      CONCLUSIONS: Classic heat stroke may demonstrate a rapidly worsening organ
      dysfunction course leading to death even though cooling procedures and intensive
      care management are promptly started.

PMID- 19404609
TI  - Combined analysis of 19 common validated type 2 diabetes susceptibility gene
      variants shows moderate discriminative value and no evidence of gene-gene
      interaction.
AB  - AIMS/HYPOTHESIS: The list of validated type 2 diabetes susceptibility variants
      has recently been expanded from three to 19. The variants identified are common
      and have low penetrance in the general population. The aim of the study is to
      investigate the combined effect of the 19 variants by applying receiver operating
      characteristics (ROC) to demonstrate the discriminatory value between glucose
      tolerant individuals and type 2 diabetes patients in a cross-sectional population
      of Danes. METHODS: The 19 variants were genotyped in three study populations: the
      population-based Inter99 study; the ADDITION study; and additional type 2
      diabetic patients and glucose-tolerant individuals. The case-control studies
      involved 4,093 type 2 diabetic patients and 5,302 glucose-tolerant individuals.
      RESULTS: Single-variant analyses demonstrated allelic odds ratios ranging from
      1.04 (95% CI 0.98-1.11) to 1.33 (95% CI 1.22-1.45). When combining the 19
      variants, subgroups with extreme risk profiles showed a threefold difference in
      the risk of type 2 diabetes (lower 10% carriers with < or =15 risk alleles vs
      upper 10% carriers with > or =22 risk alleles, OR 2.93 (95% CI 2.38-3.62, p = 1.6
      x 10(-25)). We calculated the area under a ROC curve to estimate the
      discrimination rate between glucose-tolerant individuals and type 2 diabetes
      patients based on the 19 variants. We found an area under the ROC curve of 0.60.
      Two-way gene-gene interaction showed few nominal interaction effects.
      CONCLUSIONS/INTERPRETATION: Combined analysis of the 19 validated variants
      enables detection of subgroups at substantially increased risk of type 2
      diabetes; however, the discrimination between glucose-tolerant and type 2
      diabetes individuals is still too inaccurate to achieve clinical value.

PMID- 19404611
TI  - No difference between knotless sutures and suture anchors in arthroscopic repair
      of Bankart lesions in collision athletes.
AB  - The purpose of this study was to compare the clinical results of knotless and
      knot-tying suture anchors in arthroscopic Bankart repair of collision athletes.
      Thirty-eight athletes underwent arthroscopic Bankart repairs. The mean age of the
      patients at the time of surgery was 23 years. Bio-Knot-tying anchors were used in
      18 patients, and Bio-Knotless suture anchors were used in 20 patients.
      Preoperative and postoperative evaluations were performed by Rowe scores. At the
      end of 40 months follow-up, both the knot-tying and the knotless suture anchor
      groups had similar postoperative results. There were no differences between Knot
      Tying and Knotless repair about late disengagement and re-dislocation in this
      patient group. Knotless repair provided secure and low-profile repair without
      introducing complexities to the procedure of arthroscopic knot tying one.

PMID- 19404612
TI  - Rapid oxidation of ring methyl groups is the primary mechanism of
      biotransformation of gemfibrozil by the fungus Cunninghamella elegans.
AB  - The hypolipidemic agent gemfibrozil (GEM), which has been studied for its
      metabolism in humans and animals, was investigated to elucidate its primary
      metabolism by Cunninghamella elegans. The fungus produced ten metabolites (FM1
      FM9 and FM6') from the biotransformation of GEM. Based on LC/MS/MS and NMR
      analyses, a major metabolite, FM7, was identified as 2'-hydroxymethyl GEM. FM6
      was considered to be 5'-hydroxymethyl GEM, after comparison of results LC/MS,
      LC/MS/MS, and UV absorption spectra to FM7. The combined concentration of FM6 and
      FM7 was found to increase up to 0.83 mM by day 2, and then decreased gradually
      with incubation time, followed by a noticeable increase in the biotransformation
      product, FM1, up to 0.86 mM by day 15. NMR analyses confirmed that FM1 was 2',5'
      dihydroxymethyl GEM. Further minor oxidations of the aromatic ring and carboxylic
      acid intermediates were also detected. Based upon these findings, the major
      fungal metabolic pathway for GEM is likely to occur via production of 2',5'
      dihydroxymethyl GEM from 2'-hydroxymethyl GEM. These relatively rapid and diverse
      biotransformations of GEM by C. elegans suggest that depending upon conditions,
      it may also follow a similar biodegradation fate when released into the natural
      environment.

PMID- 19404613
TI  - Mood stabilizers increase prepulse inhibition in DBA/2NCrl mice.
AB  - RATIONALE: Lithium and several antiepileptic drugs have mood-stabilizing effects
      in bipolar disorder and schizophrenia. Both disorders are characterized by
      deficits in prepulse inhibition (PPI) of the acoustic startle response.
      OBJECTIVES: Using the DBA/2 model of naturally low PPI, which is reliably
      increased by antipsychotics, five mood stabilizers in clinical use were tested to
      determine whether they would also increase PPI in this model. All drugs were
      administered intraperitoneally (i.p.) 30 min before testing. RESULTS: Lithium
      chloride (30 mg/kg), topiramate (100 and 300 mg/kg), carbamazepine (30, 60, and
      100 mg/kg), valproic acid (178 and 316 mg/kg), and lamotrigine (3, 10, and 30
      mg/kg) increased percent PPI. The antiepileptic drugs carbamazepine, valproic
      acid, and lamotrigine at high doses also decreased no-stimulus amplitudes and
      increased startle amplitudes. At high doses of carbamazepine, valproic acid, and
      lamotrigine, increases in percent PPI were independent of the increases in
      startle amplitude. CONCLUSIONS: The demonstrated efficacy of five mood
      stabilizers in the DBA/2 model of naturally low PPI points to the translational
      value of this model in predicting therapeutic activity in schizophrenia and
      bipolar disorder of compounds with diverse mechanisms of action.

PMID- 19404615
TI  - Simultaneous anhedonia and exaggerated locomotor activation in an animal model of
      depression.
AB  - RATIONALE: Anhedonia, or hyposensitivity to normally pleasurable stimuli, is a
      cardinal symptom of depression. As such, reward circuitry may comprise a
      substrate with relevance to this symptom of depression. OBJECTIVES: Our aim was
      to characterize in the rat changes in the rewarding properties of a
      pharmacological and a natural stimulus following olfactory bulbectomy (OBX), a
      pre-clinical animal model of depression. METHODS: We measured amphetamine
      enhancement of brain stimulation reward, changes in sucrose intake, as well as
      striatal cAMP response element binding protein (CREB) activity, a molecular index
      previously associated with depressant-like behavior. Moreover, since alteration
      of psychomotor activity is also a common symptom of depression, and
      psychostimulant reward and locomotion are thought to share common neurobiology,
      we used the same treatment schedule of amphetamine to probe for changes in
      locomotion. RESULTS: Our findings show that OBX produces a behavioral phenotype
      characterized by both anhedonia and exaggerated locomotor activation. Thus, we
      observed a blunted response to the rewarding properties of amphetamine (1 mg/kg,
      21 days post-lesion), a long-lasting reduction in sucrose intake and increased
      striatal CREB activity. In addition, the same dose of amphetamine, at a
      coincident time post-lesion, triggered an exaggerated response to its locomotor
      stimulant actions. CONCLUSIONS: These paradoxical findings are not consistent
      with the notion that reward and locomotion are mediated by a common substrate;
      this dissociation may be useful in modeling psychiatric disorders such as mixed
      depressive states. In addition, our findings suggest that central reward
      circuitry may constitute a possible target for rationally designed therapeutics
      for depression.

PMID- 19404618
TI  - Phosphoester hydrolysis by cerium(IV)-thiacalix[4]arene complexes and its
      application to immunoassay.
AB  - Thiacalix[4]arenetetrasulfonate was treated with Ce(IV) in water at pH 9.5 to
      give novel phosphoester-hydrolyzing complexes. The dinuclear Ce(IV) complex
      promoted the hydrolysis of p-nitrophenyl phosphate with a turnover frequency of
      6.8 h(-1) at 50 degrees C, showing fourfold higher activity than the mononuclear
      complex. The dinuclear complex was readily immobilized onto an antibody by simply
      mixing them in water, hence its phosphatase-like activity was applied to the
      color-developing reaction in immunoassay. The model assay using an antibody
      labeled with the dinuclear complex allowed the detection of as little as 10 ng
      mL(-1) of a tumor marker, Bence-Jones protein, in a 96-well microtiter plate
      format. Analysis of urine for Bence-Jones protein was performed by the proposed
      method.

PMID- 19404617
TI  - Effect of aspirin on hypothalamic-pituitary-adrenal function and on
      neuropsychological performance in healthy adults: a pilot study.
AB  - RATIONALE: Hypothalamic-pituitary-adrenal axis dysregulation predicts poor
      clinical and biochemical response to antidepressants. Antiglucocorticoids have
      therapeutic benefits but most have a troublesome adverse event profile. Aspects
      of neuropsychological performance, notably working memory, are susceptible to
      corticosteroid modulation and are impaired in depression. Aspirin has been shown
      to attenuate the adrenocorticotropic hormone (ACTH) and cortisol response to
      physiological challenge suggesting its potential to act as an augmenting agent in
      depression. OBJECTIVES: To examine the effect of sub-acute (300 mg daily for 7
      days) aspirin pre-treatment on the cortisol awakening response and the effect of
      acute (600 mg) and sub-acute aspirin on the neuroendocrine and neuropsychological
      response to the arginine vasopressin analogue, desmopressin. RESULTS: We
      demonstrated that aspirin pre-treatment did not attenuate the cortisol or ACTH
      response to desmopressin but, as hypothesised, significantly reduced the cortisol
      awakening response and improved working memory. CONCLUSIONS: Further studies to
      examine the impact of aspirin on neuropsychological performance and HPA axis
      function are warranted.

PMID- 19404616
TI  - Dissociable effects of noradrenaline, dopamine, and serotonin uptake blockade on
      stop task performance in rats.
AB  - RATIONALE: The stop-signal paradigm measures the ability to stop a motor response
      after its execution has been initiated. Impairments in inhibiting inappropriate
      behavior and prolonged stop-signal reaction times (SSRTs) are characteristic of
      several psychiatric disorders, most notably attention deficit/hyperactivity
      disorder. While there is relative consensus regarding the anatomical substrates
      of behavioral inhibition, the neurochemical imbalance responsible for the
      deficits in stopping displayed by impulsive individuals is still a matter of
      debate. OBJECTIVE: The aim of this study was to investigate the effects of
      manipulating brain monoamine levels on stop task parameters. METHODS: Lister
      hooded rats were trained on the rodent version of the stop-signal task and
      administered different monoamine transporter inhibitors: citalopram, which
      selectively blocks the serotonin transporter; atomoxetine, which selectively
      blocks the noradrenaline transporter; and GBR-12909, which selectively blocks the
      dopamine transporter (DAT), and the alpha-2 adrenergic agonist guanfacine.
      RESULTS: Atomoxetine speeded SSRT and increased accuracy for go-trials.
      Citalopram slowed go reaction time and decreased go accuracy at the highest dose
      (1 mg/kg). GBR-12909 speeded go reaction time and impaired both go and stop
      accuracy. Guanfacine negatively modulated all principal stop and go measures at
      the highest dose used (0.3 mg/kg). CONCLUSIONS: The results suggest that
      atomoxetine exerts its beneficial effects on SSRT via its action on noradrenaline
      re-uptake, as the specific DAT blocker GBR-12909 and serotonin reuptake blockade
      had only minor effects on SSRT. The speeding of the go reaction time by dopamine
      reuptake blockade is consistent with the hypothesis that the hypothetical stop
      and go processes are modulated by distinct monoaminergic systems.

PMID- 19404620
TI  - Multisensory integration of drumming actions: musical expertise affects perceived
      audiovisual asynchrony.
AB  - We investigated the effect of musical expertise on sensitivity to asynchrony for
      drumming point-light displays, which varied in their physical characteristics
      (Experiment 1) or in their degree of audiovisual congruency (Experiment 2). In
      Experiment 1, 21 repetitions of three tempos x three accents x nine audiovisual
      delays were presented to four jazz drummers and four novices. In Experiment 2,
      ten repetitions of two audiovisual incongruency conditions x nine audiovisual
      delays were presented to 13 drummers and 13 novices. Participants gave forced
      choice judgments of audiovisual synchrony. The results of Experiment 1 show an
      enhancement in experts' ability to detect asynchrony, especially for slower
      drumming tempos. In Experiment 2 an increase in sensitivity to asynchrony was
      found for incongruent stimuli; this increase, however, is attributable only to
      the novice group. Altogether the results indicated that through musical practice
      we learn to ignore variations in stimulus characteristics that otherwise would
      affect our multisensory integration processes.

PMID- 19404614
TI  - The effect of increased serotonergic neurotransmission on aggression: a critical
      meta-analytical review of preclinical studies.
AB  - RATIONALE: The role of serotonin (5-HT) on aggression has been extensively
      studied; nonetheless, the role of this neurotransmitter in aggression is still
      inconclusive. OBJECTIVES: The current meta-analytical review investigated the
      role of increased 5-HT neurotransmission in aggression. METHODS: Preclinical
      studies using serotonin reuptake inhibitors, 5-hydroxytryptophan, L-tryptophan,
      or serotonin (5-HT) to increase 5-HT levels were included in this meta-analysis.
      An overall effect of serotonin on aggression was calculated, and the role of
      several moderator variables was analyzed. RESULTS: A total of 218 effect sizes
      revealed that increased 5-HT had an overall significant inhibitory effect on
      aggression (r = 0.3). The results showed that increased 5-HT had the strongest
      inhibitory effect on aggression when (1) a specific strain or species (e.g., Long
      Evans) was used; (2) aggression was offensive or predatory and/or induced by
      administration of 5,7-dihydroxytryptamine or p-chlorophenylalanine; (3)
      zimelidine, sertraline, L-tryptophan, citalopram, or 5-HT were used to increase 5
      HT; (4) treatment was acute; (5) long chronic treatment durations were used; and
      (6) time between last injection and behavior testing was within 8 h before or
      after peak plasma concentration of drug. In contrast, the results revealed that
      increased-5-HT-facilitated aggression could be predicted when (1) Wistar rats,
      (2) social isolation or stress to induce aggression, and/or (3) animals treated
      for less than 3 weeks were used. CONCLUSIONS: Although 5-HT has an overall
      inhibitory effect on aggression, the animal's genetic background, drug, treatment
      time, aggression inducing paradigm, and aggression type are critical variables
      that influence and modify this effect.

PMID- 19404622
TI  - Limitations of feedforward control in multiple-phase steering movements.
AB  - When attempting to perform bi-phasic steering movements (such as a lane change)
      in the absence of visual and inertial feedback, drivers produce a systematic
      heading error in the direction of the lane change (Wallis et al., Curr Biol
      12(4):295-299, 2002; J Exp Psychol Hum Percept Perform 33(55):1127-1144, 2007).
      Theories of steering control which employ exclusively open-loop control
      mechanisms cannot accommodate this finding. In this article we show that a
      similar steering error occurs with obstacle avoidance, and offer compelling
      evidence that it stems from a seemingly general failure of human operators to
      correctly internalise the dynamics of the steering wheel. With respect to lateral
      position, the steering wheel is an acceleration control device, but we present
      data indicating that drivers treat it as a rate control device. Previous findings
      from Wallis et al. can be explained the same way. Since an open-loop control
      mechanism will never succeed when the dynamics of the controller are internalised
      improperly, we go on to conclude that regular, appropriately timed sensory
      feedback-predominantly from vision-is necessary for regulating heading, even
      during well-practiced, everyday manoeuvres such as lane changing and obstacle
      avoidance.

PMID- 19404621
TI  - Preservation of crossmodal selective attention in healthy aging.
AB  - The goal of the present study was to determine if older adults benefited from
      attention to a specific sensory modality in a voluntary attention task and
      evidenced changes in voluntary or involuntary attention when compared to younger
      adults. Suppressing and enhancing effects of voluntary attention were assessed
      using two cued forced-choice tasks, one that asked participants to localize and
      one that asked them to categorize visual and auditory targets. Involuntary
      attention was assessed using the same tasks, but with no attentional cues. The
      effects of attention were evaluated using traditional comparisons of means and
      Cox proportional hazards models. All analyses showed that older adults benefited
      behaviorally from selective attention in both visual and auditory conditions,
      including robust suppressive effects of attention. Of note, the performance of
      the older adults was commensurate with that of younger adults in almost all
      analyses, suggesting that older adults can successfully engage crossmodal
      attention processes. Thus, age-related increases in distractibility across
      sensory modalities are likely due to mechanisms other than deficits in
      attentional processing.

PMID- 19404623
TI  - The hand's automatic pilot can update visual information while the eye is in
      motion.
AB  - When participants reach for a target, their hand can adjust to a change in target
      position that occurs while their eyes are in motion (the hand's automatic pilot)
      even though they are not aware of the target's displacement (saccadic suppression
      of perceptual experience). However, previous studies of this effect have
      displayed the target without interruption, such that the new target position
      remains visible during the fixation that follows the saccade. Here we test
      whether a change in target position that begins and ends during the saccade can
      be used to update aiming movements. We also ask whether such information can be
      acquired from two targets at a time. The results showed that participants
      responded to single and double target jumps even when these targets were
      extinguished prior to saccade termination. The results imply that the hand's
      automatic pilot is updated with new visual information even when the eye is in
      motion.

PMID- 19404624
TI  - Coordinate transformations for hand-guided saccades.
AB  - Relatively little is known about the role of proprioception in eye-hand
      coordination. In a previous article (Ren et al. J Neurophysiol 96:1464-1477,
      2006), we observed anisotropic (direction-dependent) saccade overshoots to hand
      held targets during active, but not passive hand movements. We hypothesized that
      these errors arose from a limb-centered anisotropic efference copy which was
      transformed (uncompensated) into head coordinates for saccade control. Here, we
      tested this hypothesis and the role of head orientation signals in this
      transformation, by dissociating limb coordinates from head coordinates. Twelve
      human subjects made saccades to hand-held targets actively placed at eight radial
      locations on a frontally placed table in a dark room with four conditions: (1)
      right hand (body and head centered), (2) left hand (body and head centered), (3)
      right hand (head tilted counter-clockwise), (4) right hand (head tilted
      clockwise). In condition 1, we observed the same anisotropic pattern of
      overshooting errors-approximately along the axis of the forearm-that we reported
      previously. Overall, these amplitude errors were much smaller for the left hand.
      However, the anisotropic pattern was observed for both hands, but reversed
      symmetrically between the right versus left hand. Head tilt did not cause any
      systematic errors in saccade direction. Moreover, during head tilt, the
      anisotropic amplitude errors-while showing some distortions-did not rotate with
      the head. These findings suggest that transformations of somatosensory
      information into oculomotor coordinates account for head orientation, and that
      the anisotropic amplitude errors in hand-guided saccades arise in limb
      coordinates.

PMID- 19404625
TI  - Translating nociceptive processing into human pain models.
AB  - As volunteers can easily communicate quality and intensity of painful stimuli,
      human pain models appear to be ideally suited to test analgesic compounds, but
      also to study pain mechanisms. Acute stimulation of nociceptors under physiologic
      conditions has proven not to be of particular use as an experimental pain model.
      In contrast, if the experimental models include sensitization of the peripheral
      or central pain processing they may indeed mimic certain aspects of chronic pain
      conditions. Peripheral inflammatory conditions can be induced experimentally with
      sensitization patterns correlating to clinical inflammatory pain. There are also
      well-characterized models of central sensitization, which mimic aspects of
      neuropathic pain patients such as touch evoked allodynia and punctate
      hyperalgesia. The main complaint of chronic pain patients, however, is
      spontaneous pain, but currently there is no human model available that would
      mimic chronic inflammatory or neuropathic pain. Thus, although being helpful for
      proof of concept studies and dose finding, current human pain models cannot
      replace patient studies for testing efficacy of analgesic compounds.

PMID- 19404627
TI  - Differential effects of delay upon visually and haptically guided grasping and
      perceptual judgments.
AB  - Experiments with visual illusions have revealed a dissociation between the
      systems that mediate object perception and those responsible for object-directed
      action. More recently, an experiment on a haptic version of the visual size
      contrast illusion has provided evidence for the notion that the haptic modality
      shows a similar dissociation when grasping and estimating the size of objects in
      real-time. Here we present evidence suggesting that the similarities between the
      two modalities begin to break down once a delay is introduced between when people
      feel the target object and when they perform the grasp or estimation. In
      particular, when grasping after a delay in a haptic paradigm, people scale their
      grasps differently when the target is presented with a flanking object of a
      different size (although the difference does not reflect a size-contrast effect).
      When estimating after a delay, however, it appears that people ignore the size of
      the flanking objects entirely. This does not fit well with the results commonly
      found in visual experiments. Thus, introducing a delay reveals important
      differences in the way in which haptic and visual memories are stored and
      accessed.

PMID- 19404626
TI  - Differential effects of TRPV channel block on polymodal activation of rat
      cutaneous nociceptors in vitro.
AB  - The capsaicin receptor TRPV1 is a polymodal sensory transducer molecule in the
      pain pathway. TRPV1 integrates noxious heat, tissue acidosis and chemical stimuli
      which are all known to cause pain. Studies on TRPV1-deficient mice suggest that
      TRPV1 is essential for acid sensing by nociceptors and for thermal hyperalgesia
      in inflammation of the skin, but not for transducing noxious heat. After TRPV1,
      other TRPV channels were cloned with polymodal properties and sensitivity to
      noxious heat, named TRPV2, TRPV3 and TRPV4. While TRPV3 and TRPV4 are
      predominantly warm sensors, TRPV2's threshold is in the noxious range (>52
      degrees C). However, mice deficient of TRPV2 and TRPV1 or TRPV3 or TRPV4 show no
      major impairment of noxious heat sensing. Ruthenium red, a water soluble
      polycationic dye, was found to block the pore of the capsaicin-operated cation
      channel TRPV1 thus interfering with all polymodal ways of TRPV1 activation.
      Antagonistic effects of the dye were subsequently described on many other TRP
      channels, especially on the heat-sensitive ones of the vanilloid family, TRPV2,
      TRPV3 and TRPV4. In this study, we used the rat skin-nerve preparation to define
      the possible actions of ruthenium red on the proton, capsaicin and noxious heat
      activation of native polymodal nociceptors. Ruthenium red was found to suppress
      only the capsaicin-induced excitation and desensitization of these nerve endings.
      On the contrary, the proton and heat-induced discharge responses of the single
      fibres were not influenced. Additionally, we found that the dye concentration
      dependently increases the excitability of the neurons resulting in ongoing
      activity and burstlike discharge. These differential results are discussed in the
      light of recent findings from transgenic mouse models, and they point once more
      to major (pharmacological) differences between cellular models of nociception,
      including spinal ganglion neuron and transfected cell lines, and the real native
      nerve endings.

PMID- 19404628
TI  - A comparison of motor skill learning and retention in younger and older adults.
AB  - The goal of the current study was to explore learning and short-term retention
      using a modified serial reaction time task. The multi-finger sequence task was
      designed to present repeated and random sequences in a completely interleaved
      fashion, giving participants within block, variable practice, on the two types of
      sequences. Eighteen younger adults (M(age) = 24 years) and 15 older adults
      (M(age) = 65 years) participated in the experiment. Participants were asked to
      respond on a piano keyboard to a visual stimulus that appeared in one of four
      squares on the computer screen. They were not informed that one of the sequences
      presented would repeat. Sequence-specific learning, within-day and across-days,
      was inferred from differences in accuracy and reaction time between repeated and
      random sequences. Age equivalence was observed in sequence-specific learning and
      retention across days, and suggests that older adults may benefit from variable
      practice.

PMID- 19404629
TI  - Saccades and reaches, behaving differently.
AB  - Previously, we have shown, both in humans and monkeys, that the latencies of
      exogenously generated saccades decrease with an increase in the number of
      response alternatives (Lawrence et al. in J Vis 8:26, 1-7, 2008). Because this
      pattern of latencies was in the direction opposite that predicted by Hick (Q J
      Exp Psychol 4:11-26, 1952), we termed the effect an "anti-Hick's" effect. In
      contrast, previous research has shown that reach latencies increase with an
      increase in response alternatives (e.g., Wright et al. in Exp Brain Res 179:475
      496, 2007). Given that there are known interactions between the saccade and reach
      systems, we examined whether the direction of the relationship between latencies
      and response alternatives differed when saccades and reaches are concomitantly
      executed. Interestingly, we found that the pattern of latencies nevertheless
      persisted in a visually guided saccade and reach task. These results place an
      important constraint on the anti-Hick's effect, suggesting not only that the
      effect is localized within the saccade system, but also that it is localized in
      the saccade system at a level in which saccade and reach signals do not interact.

PMID- 19404631
TI  - Impact of CYP2C19 phenotypes on escitalopram metabolism and an evaluation of
      pupillometry as a serotonergic biomarker.
AB  - PURPOSE: To investigate the impact of cytochrome P450 2C19 (CYP2C19) phenotypes
      on escitalopram metabolism and to evaluate pupillometry as a serotonergic
      biomarker. METHODS: This was a double-blind, crossover design study with single
      and multiple doses of 10 mg escitalopram and placebo in panels of CYP2C19
      extensive (EM) and poor metabolisers (PM). Pupillometry was measured by a
      NeurOptics Pupillometer-PLR. RESULTS: Five PM and eight EM completed the study.
      The CYP2C19 phenotype significantly affected the metabolism of escitalopram. The
      area under the time-plasma concentration curve (AUC(0-24)) was 1.8-fold higher in
      PM than in EM after both single and multiple doses. Escitalopram treatment did
      not affect the maximum pupil size, but it did statistically significantly
      decrease the relative amplitude of the pupil light reflex compared to the
      placebo; this effect was equal in both phenotype groups. CONCLUSIONS: The CYP2C19
      polymorphism affects escitalopram metabolism, but the difference does not justify
      dose adjustment. The puzzling results from pupillometry can be due to interplay
      between a central and a local serotonergic effect. Based on these results,
      pupillometry can not be recommended as a serotonergic biomarker.

PMID- 19404630
TI  - Effect of reduced cutaneous cues on motion perception and postural control.
AB  - To investigate whether the sensory perception could be a more direct assessment
      of sensory deficit as oppose to the postural performance, we examined the effect
      of reduced cutaneous cues on motion perception and motion control. The subject
      was translated in a mediolateral direction with a single sinusoidal acceleration
      at a stimulus frequency of 0.25 Hz with a peak acceleration magnitude ranging
      from 0.25 to 8 mG in the dark. Two different plantar cutaneous conditions were
      provided: the control condition (barefoot) and the reduced cutaneous condition
      (foot on a spongy surface). For each foot-sole sensory condition, the subject
      completed six sets of 33 randomly ordered translation stimuli. After each
      translational stimulus, the subject reported their perceived direction of motion
      by pressing a hand-held button. The center of pressure (COP) and joint kinematics
      of the quiet stance were also measured. The results showed a significant increase
      in perception threshold as well as COP variation in the anteroposterior direction
      in the reduced cutaneous cue trials. However, a non-significant increase in COP
      in the mediolateral direction was shown. Multivariate covariance analysis of
      joint kinematics showed changes in postural coordination, such as increased
      reliance on hip strategy under reduced cutaneous cues condition, that have not
      been differentiated by univariate measures. The observed discrepancy in the
      significance of the contribution of plantar cutaneous cues to the detection
      threshold and the COP variation implies that the 'perception' could provide more
      direct and sensitive assessment of the sensory degradation than the 'action'.

PMID- 19404632
TI  - Tolerability and pharmacokinetics of non-fixed and fixed combinations of
      artesunate and amodiaquine in Malaysian healthy normal volunteers.
AB  - OBJECTIVE: There is limited pharmacokinetic data available for the combination
      artesunate + amodiaquine, which is used widely to treat uncomplicated malaria.
      This study examines the bioavailability and tolerability of a fixed (200 mg
      artesunate + 540 mg amodiaquine) and loose (200 mg + 612 mg) combination with a
      2x2 cross-over design in 24 healthy volunteers. METHODS: Parent compounds and
      metabolites [dihydroartemisinin (DHA) and desethylamodiaquine (DEAQ)] were
      measured by high-performance liquid chromatography-electrochemical detection, and
      the area under the curve (AUC)(0-t) and C(max) were compared by an analysis of
      variance (ANOVA) based on geometric least square means using the Schuirmann two
      one-sided test. RESULTS: The AUC(0-t) for total DHA and DEAQ were 1522 +/- 633
      and 30021 +/- 14211 ng h/ml for the fixed products and 1688 +/- 767 and 40261 +/-
      19824 ng h/ml (mean +/- standard deviation) for the loose products. The ANOVA
      showed no statistical differences except for sequence effect for DHA. The values
      obtained with the fixed product were within the 125% bioequivalent limits but
      extend below the 80% bioequivalence limits. CONCLUSION: Both combinations were
      well tolerated and had comparable pharmacokinetic profiles; differences are
      unlikely to be clinically relevant.

PMID- 19404633
TI  - Determination of axonal transport velocities via image cross- and
      autocorrelation.
AB  - On their way to the synapse and back, neuronal proteins are carried in cargo
      vesicles along axons and dendrites. Here, we demonstrate that the key parameters
      of axonal transport, i.e., particle velocities and pausing times can be read out
      from CCD-camera images automatically. In the present study, this is achieved via
      cross- and autocorrelation of kymograph columns. The applicability of the method
      was measured on simulated kymographs and data from axonal transport timeseries of
      mRFP-labeled synaptophysin. In comparing outcomes of velocity determinations via
      a performance parameter that is analogous to the signal-to-noise ratio (SNR)
      definition, we find that outcomes are dependent on sampling, particle numbers and
      signal to noise of the kymograph. Autocorrelation of individual columns allows
      exact determination of pausing time populations. In contrast to manual tracking,
      correlation does not require experience, a priori assumptions or disentangling of
      individual particle trajectories and can operate at low SNR.

PMID- 19404634
TI  - Gating the pore of potassium leak channels.
AB  - A key feature of potassium channel function is the ability to switch between
      conducting and non-conducting states by undergoing conformational changes in
      response to cellular or extracellular signals. Such switching is facilitated by
      the mechanical coupling of gating domain movements to pore opening and closing.
      Two-pore domain potassium channels (K(2P)) conduct leak or background potassium
      selective currents that are mostly time- and voltage-independent. These channels
      play a significant role in setting the cell resting membrane potential and,
      therefore modulate cell responsiveness and excitability. Thus, K(2P) channels are
      key players in numerous physiological processes and were recently shown to also
      be involved in human pathologies. It is well established that K(2P) channel
      conductance, open probability and cell surface expression are significantly
      modulated by various physical and chemical stimuli. However, in understanding how
      such signals are translated into conformational changes that open or close the
      channels gate, there remain more open questions than answers. A growing line of
      evidence suggests that the outer pore area assumes a critical role in gating
      K(2P) channels, in a manner reminiscent of C-type inactivation of voltage-gated
      potassium channels. In some K(2P) channels, this gating mechanism is facilitated
      in response to external pH levels. Recently, it was suggested that K(2P) channels
      also possess a lower activation gate that is positively coupled to the outer pore
      gate. The purpose of this review is to present an up-to-date summary of research
      describing the conformational changes and gating events that take place at the
      K(2P) channel ion-conducting pathway during the channel regulation.

PMID- 19404637
TI  - Continuous power generation and microbial community structure of the anode
      biofilms in a three-stage microbial fuel cell system.
AB  - A mediator-less three-stage two-chamber microbial fuel cell (MFC) system was
      developed and operated continuously for more than 1.5 years to evaluate
      continuous power generation while treating artificial wastewater containing
      glucose (10 mM) concurrently. A stable power density of 28 W/m(3) was attained
      with an anode hydraulic retention time of 4.5 h and phosphate buffer as the
      cathode electrolyte. An overall dissolved organic carbon removal ratio was about
      85%, and coulombic efficiency was about 46% in this MFC system. We also analyzed
      the microbial community structure of anode biofilms in each MFC. Since the
      environment in each MFC was different due to passing on the products to the next
      MFC in series, the microbial community structure was different accordingly. The
      anode biofilm in the first MFC consisted mainly of bacteria belonging to the
      Gammaproteobacteria, identified as Aeromonas sp., while the Firmicutes dominated
      the anode biofilms in the second and third MFCs that were mainly fed with
      acetate. Cyclic voltammetric results supported the presence of a redox
      compound(s) associated with the anode biofilm matrix, rather than mobile
      (dissolved) forms, which could be responsible for the electron transfer to the
      anode. Scanning electron microscopy revealed that the anode biofilms were
      comprised of morphologically different cells that were firmly attached on the
      anode surface and interconnected each other with anchor-like filamentous
      appendages, which might support the results of cyclic voltammetry.

PMID- 19404636
TI  - Origin and evolution of the vertebrate leukocyte receptors: the lesson from
      tunicates.
AB  - Two selected receptor genes of the immunoglobulin superfamily (IgSF), one CTX/JAM
      family member, and one poliovirus receptor-like nectin that have features of
      adhesion molecules can be expressed by Ciona hemocytes, the effectors of
      immunity. They can also be expressed in the nervous system (CTX/JAM) and in the
      ovary (nectin). The genes encoding these receptors are located among one set of
      genes, spread over Ciona chromosomes 4 and 10, and containing other IgSF members
      homologous to those encoded by genes present in a tetrad of human (1, 3 + X, 11,
      21 + 19q) or bird chromosomes (1, 4, 24, 31) that include the leukocyte receptor
      complex. It is proposed that this tetrad is due to the two rounds of duplication
      that affected a single prevertebrate ancestral region containing a primordial
      leukocyte receptor complex involved in immunity and other developmental
      regulatory functions.

PMID- 19404638
TI  - Optimization of L: -methionine feeding strategy for improving S-adenosyl-L: 
      methionine production by methionine adenosyltransferase overexpressed Pichia
      pastoris.
AB  - The recombinant Pichia pastoris harboring an improved methionine
      adenosyltransferase (MAT) shuffled gene was employed to biosynthesize S-adenosyl
      L: -methionine (SAM). Two L: -methionine (L: -Met) addition strategies were used
      to supply the precursor: the batch addition strategy (L: -Met was added
      separately at three time points) and the continuous feeding strategies (L: -Met
      was fed continuously at the rate of 0.1, 0.2, and 0.5 g l(-1) h(-1),
      respectively). SAM accumulation, L: -Met conversion rate, and SAM productivity
      with the continuous feeding strategies were all improved over the batch addition
      strategy, which reached 8.46 +/- 0.31 g l(-1), 41.7 +/- 1.4%, and 0.18 +/- 0.01 g
      l(-1) h(-1) with the best continuous feeding strategy (0.2 g l(-1) h(-1)),
      respectively. The bottleneck for SAM production with the low L: -Met feeding rate
      (0.1 g L(-1) h(-1)) was the insufficient L: -Met supply. The analysis of the key
      enzyme activities indicated that the tricarboxylic acid cycle and glycolytic
      pathway were reduced with the increasing L: -Met feeding rate, which decreased
      the adenosine triphosphate (ATP) synthesis. The MAT activity also decreased as
      the L: -Met feeding rate rose. The reduced ATP synthesis and MAT activity were
      probably the reason for the low SAM accumulation when the L: -Met feeding rate
      reached 0.5 g l(-1) h(-1).

PMID- 19404635
TI  - Gating mechanisms in Cys-loop receptors.
AB  - The Cys-loop receptor superfamily of ligand-gated ion channels has a prominent
      role in neuronal signalling. These receptors are pentamers, each subunit
      containing ten beta-strands in the extracellular domain and four alpha-helical
      transmembrane domains (M1-M4). The M2 domain of each subunit lines the intrinsic
      ion channel pore and residues within the extracellular domain form ligand binding
      sites. Ligand binding initiates a conformational change that opens the ion
      selective pore. The coupling between ligand binding in the extracellular domain
      and opening of the intrinsic ion channel pore located in the membrane is not
      fully understood. Several loop structures, such as loop 2, the Cys-loop, the pre
      M1 region and the M2-M3 loop have been implicated in receptor activation. The
      current "conformational change wave" hypothesis suggests that binding of a ligand
      initiates a rotation of the beta-sheets around an axis that passes through the
      Cys-loop. Due to this rotation, the Cys-loop and loop 2 are displaced. Movement
      of the M2-M3 loop then twists the M2 domain leading to a separation of the
      helices and opening of the pore. The publication of a crystal structure of an
      acetylcholine binding protein and the refined structure of the Torpedo marmorata
      acetylcholine receptor have improved the understanding of the mechanisms and
      structures involved in coupling ligand binding to channel gating. In this review,
      the most recent findings on some of these loop structures will be reported and
      discussed in view of their role in the gating mechanism.

PMID- 19404639
TI  - Large bone distractor for open reconstruction of articular fractures of the
      calcaneus.
AB  - The results of operative treatment of two groups of patients with articular
      fractures of the calcaneus were evaluated. Twenty-three cases were treated
      surgically using a standard reconstruction procedure. In the second group of 19
      patients a large bone distractor was used; it held the soft tissue flap
      retracted, while aiding in articular and tuberosity fragment reduction and
      increasing visualisation by distraction of the posterior talocalcaneal joint.
      After a year, the anatomical and functional results, together with the operative
      time, were evaluated. All fractures healed with good or very good anatomical
      results. All cases, except those with complications (n = 3), achieved good (n =
      28) or very good (n = 11) functional scoring. The distractor group had
      significantly shorter operative times, and less manpower was needed during
      surgery. We conclude that the large bone distractor is a useful tool in open
      reconstruction of articular calcaneal fractures.

PMID- 19404640
TI  - Wilms' tumor gene 1 (WT1) expression in subtypes of acute lymphoblastic leukemia
      (ALL) of adults and impact on clinical outcome.
AB  - Wilms' tumor gene 1 (WT1) is gaining increasing attention as a therapeutic target
      molecule due to its common expression in acute leukemias and its involvement in
      cell proliferation. Here, we reported on WT1 messenger RNA expression levels at
      diagnosis in a series of 238 adult acute lymphoblastic leukemia (ALL) samples of
      various subtypes and clinical outcome. WT1 expression was found in 219 out of 238
      ALL samples (92%). Compared to a cohort of acute myeloid leukemia patients, the
      median WT1 expression level in ALL was significantly lower with large variations
      among different ALL subgroups. Specifically, WT1 expression levels were low in
      mature B-ALL and highest in ALL cases with co-expression of myeloid markers,
      making it a useful therapeutic target molecule in adult ALL with the exception of
      mature B-ALL. Cox regression analysis, considering ALL phenotype as well as
      molecular-cytogenetic subsets, revealed no independent prognostic role of WT1
      expression level for disease-free and overall survival.

PMID- 19404641
TI  - A phase II study of uracil-tegafur plus doxorubicin and prognostic factors in
      patients with unresectable biliary tract cancer.
AB  - PURPOSE: The purpose of this study was to clarify the safety and efficacy of
      combination chemotherapy of uracil-tegafur (UFT) and doxorubicin (UFD regimen),
      and to identify the prognostic factors in patients with unresectable advanced
      biliary tract cancer who received systemic chemotherapy. METHODS: Patients with
      histologically or cytologically confirmed, measurable biliary tract cancer,
      including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer,
      and ampullary cancer, who were not suitable candidates for surgery, were eligible
      for the study. Patients received oral UFT at 300 mg/m(2) per day divided into two
      doses on days 1-14 and intravenous doxorubicin at 30 mg/m(2) on day 1. This cycle
      was repeated every 21 days. The relationship between the patient characteristics
      and the prognosis was examined. Univariate and multivariate analyses were
      conducted to identify the prognostic factors associated with survival. RESULTS:
      Sixty-one patients from 12 institutions were enrolled in the late phase II study
      between April 2005 and March 2006. Of the 61 patients, 4 patients had partial
      responses, for an objective response rate of 6.6% (95% CI: 1.8-15.9%); 28
      patients had stable disease, 27 had progressive diseases, and 2 patients were not
      evaluated. The median progression-free survival was 1.6 months, and the overall
      median survival time was 6.5 months. In the 85 patients who received this UFD
      chemotherapy in previous and late phase II studies, multivariate analysis
      revealed the ECOG performance status 1 (P = 0.001), gallbladder as the primary
      cancer site (P = 0.014), T-factor 4 of the TNM classification (P = 0.035), and
      elevated serum lactate dehydrogenase levels (P = 0.043) as being associated with
      a significantly shorter survival. CONCLUSIONS: Combination chemotherapy of UFT
      and doxorubicin had minimum activity against advanced biliary tract cancer.
      Performance status was identified as the most important prognostic factor in
      patients who received systemic chemotherapy.

PMID- 19404642
TI  - Response of imatinib-resistant extra-abdominal aggressive fibromatosis to
      sunitinib: case report and review of the literature on response to tyrosine
      kinase inhibitors.
AB  - PURPOSE: Aggressive fibromatosis (AF) is usually a slowly growing locally
      invasive tumor, but may exhibit a much more aggressive phenotype. The role of
      chemotherapy in AF is not well defined, but can be useful in some cases. We
      examined the response of a case to both imatinib and sunitinib. METHODS: We
      report a case of an aggressive multicentric extra-abdominal AF that was
      responsive to sunitinib, but resistant to imatinib. RESULTS: A 23-year-old woman
      developed painful multifocal AF of both legs and gluteal muscles that progressed
      after surgery and treatment with methotrexate/vinblastine and pegylated-liposomal
      doxorubicin. She received six cycles of ifosfamide/etoposide (IMV), and obtained
      a good response with elimination of pain. After 5 months, she developed
      progression and again received six cycles of IMV, with cessation of symptoms.
      After 13 months, tumors recurred. Although the AF was symptomatic and
      progressing, she was hesitant to receive chemotherapy and began treatment with
      sunitinib 50 mg/day for 28 days of a 42-day cycle. At 4 months, she could walk on
      her heels without pain. After 13 months of sunitinib, therapy was changed to
      imatinib 400 mg/day; after 7 days she noticed increasing pain in the AF lesions
      and decreased knee flexibility. Imatinib was continued, but after 2 months of
      imatinib, she could only walk a few steps due to pain. Sunitinib was reinstituted
      at 37.5 mg/day and symptoms improved within 1.5 weeks, with a marked reduction of
      symptoms at 1 month. She was doing well with a normal activity level, 32 months
      after initially beginning sunitinib. CONCLUSIONS: We conclude that sunitinib may
      be useful in some cases of AF.

PMID- 19404643
TI  - ABT-737, a BH3 mimetic, induces glutathione depletion and oxidative stress.
AB  - PURPOSE: This study assessed the role of oxidative stress and loss of glutathione
      in ABT-737-induced apoptosis. METHODS: Jurkat human acute lymphocytic leukemia
      cells and HeLa cells transfected with a tet-regulated Bcl-2 expression system
      were treated with ABT-737 or its less active stereoisomer. GSH concentrations,
      intracellular reactive oxygen species (ROS), caspase activation and apoptotic DNA
      fragmentation were measured. RESULTS: ABT-737 induced oxidative stress through
      decreased GSH and increased intracellular hydrogen peroxide and superoxide
      levels. Apoptotic DNA fragmentation and caspase activation were the consequences
      of this oxidative stress. Combining ABT-737 with ROS-inducing agents such as
      adaphostin or etoposide enhanced cell death. CONCLUSIONS: These results
      demonstrate that inhibition of Bcl-2 causes a loss of GSH, an increase in ROS,
      caspase activation and subsequent apoptosis. Clinically, redox alterations as a
      consequence of Bcl-2 inhibition by ABT-737 should be considered in devising
      combination therapies with this novel agent or its derivatives.

PMID- 19404646
TI  - Increased expression of CD154 and FAS in SLE patients' lymphocytes.
AB  - An increased level of apoptotic material and B cell activation leading to
      autoantibody production are hallmarks of systemic lupus erythematoses (SLE).
      Increased FAS expression, apoptosis, and CD154-mediated signaling, enabling T-B
      cell interaction are involved in the pathogenesis of SLE. This study addresses
      the expression profile of CD154 and FAS in the peripheral blood of patients with
      SLE, rheumatoid arthritis (RA) and normal healthy control donors. Surface markers
      on peripheral blood T and B cells from patients and healthy control donors were
      assessed using flow cytometry. The expression of CD154 and FAS were significantly
      increased in T and B cells of SLE patients as compared to healthy control donors
      and RA patients. In SLE and RA patients, FAS expression strongly correlated with
      CD154 expression on T cells, which was not found in healthy control donors. FAS
      expression was also associated with the occurrence of anti-DNA antibodies. We
      demonstrate high CD154 and FAS expression as a characteristic feature of SLE.
      This pattern may reflect simultaneous activation of apoptosis and activation of B
      T cell interaction in SLE.

PMID- 19404647
TI  - Which portion of the natural panorama is used for view-based navigation in the
      Australian desert ant?
AB  - Ants that forage in visually rich environments often develop idiosyncratic routes
      between their nest and a profitable foraging ground. Such route knowledge is
      underpinned by an ability to use visual landmarks for guidance and place
      recognition. Here we ask which portions of natural visual scenes are essential
      for visually guided navigation in the Australian desert ant Melophorus bagoti
      whose foragers navigate through a habitat containing grass tussocks, shrubs and
      trees. We captured M. bagoti foragers after they had returned to their nest from
      a feeder, but before they had entered their nest, and tested their ability to
      home accurately from a series of release locations. We used this simple release
      paradigm to investigate visually guided navigation by monitoring the accuracy of
      nestwards orientation when parts of the ants' visual field were obscured. Results
      show that the lower portion of the visual panorama is more important for visually
      guided homing than upper portions. Analysis of panoramic images captured from the
      release and nest locations support the hypothesis that the important visual
      information is provided by the panoramic contour, where terrestrial objects
      contrast against sky, rather than by a limited number of salient landmarks such
      as tall trees.

PMID- 19404645
TI  - Connexins participate in the initiation and progression of atherosclerosis.
AB  - Connexins are members of a large family of transmembrane proteins that form
      hemichannels or gap junctions. These channels allow the exchange of ions and
      small metabolites between the cytosol and extracellular space or between
      neighboring cells. Connexins are important in vascular physiology; they support
      radial and longitudinal cell-to-cell communication in the vascular wall. Four
      connexins are expressed in the vascular wall: Cx37, Cx40, Cx43, and Cx45. Their
      expression is not uniform in all blood vessels and varies with vascular territory
      and species. Significant changes in the expression pattern of vascular connexins
      have been described during the development of atherosclerosis, a progressive
      inflammatory disease. In this review, we provide an overview of (1) the tools
      used to study the involvement of connexins in atherosclerosis, (2) the
      participation of connexins in atherogenesis, (3) the increasing interest of a
      polymorphism in the human connexin37 gene as marker of cardiovascular disease,
      and (4) the possible therapeutic implications of connexins.

PMID- 19404648
TI  - Comparison of implantable central venous ports with catheter insertion via
      external jugular cut down and subclavian puncture in children: single center
      experience.
AB  - PURPOSE: The purpose of this study is to demonstrate the efficacy, safety and
      long-term advantages of catheter insertion via external jugular vein (EJV) cut
      down for implantable central venous port in children. MATERIALS AND METHODS:
      Thirty-nine central venous ports were implanted with catheter insertion via
      subclavian puncture in the children (group 1) with average age of 4.2 years.
      Forty-three were done by inserting the catheter via EJV cut down in the children
      (group 2) with average age of 4.8 years. Ports remained functional for a total of
      11,890 patient days in group 1 and 15,743 patient days in group 2. RESULTS: The
      ports were unplanned removed in 28.2% of patients (11/39) in group 1 with
      comparison of 7.0% of patients (3/43; p < 0.01) in group 2. Five patients (12.8%
      of ports implanted) suffered an infectious complication in group 1 and just one
      patient (2.3% of ports implanted; p < 0.01) occurred in group 2. Permanent
      aspiration occlusion occurred in every two patients for each group with incidence
      of 5.1% in group 1 and 4.7% in group 2. Catheter fracture occurred in three
      patients in group 1 (7.7%). One case with catheter disconnected to the port was
      found in group 1 (2.6%). The disconnected catheter was removed from right
      ventricle by interventional therapy. CONCLUSION: Insertion of the catheter via
      the EJV cut down for implantable central venous port is significant better than
      insertion of the catheter via subclavian puncture in children.

PMID- 19404644
TI  - Obstructive sleep apnea, immuno-inflammation, and atherosclerosis.
AB  - Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder leading to
      cardiovascular and metabolic complications. OSA is also a multicomponent
      disorder, with intermittent hypoxia (IH) as the main trigger for the associated
      cardiovascular and metabolic alterations. Indeed, recurrent pharyngeal collapses
      during sleep lead to repetitive sequences of hypoxia-reoxygenation. This IH
      induces several consequences such as hemodynamic, hormonometabolic, oxidative,
      and immuno-inflammatory alterations that may interact and aggravate each other,
      resulting in artery changes, from adaptive to degenerative atherosclerotic
      remodeling. Atherosclerosis has been found in OSA patients free of other
      cardiovascular risk factors and is related to the severity of nocturnal hypoxia.
      Early stages of artery alteration, including functional and structural changes,
      have been evidenced in both OSA patients and rodents experimentally exposed to
      IH. Impaired vasoreactivity with endothelial dysfunction and/or increased
      vasoconstrictive responses due to sympathetic, endothelin, and renin-angiotensin
      systems have been reported and also contribute to vascular remodeling and
      inflammation. Oxidative stress, inflammation, and vascular remodeling can be
      directly triggered by IH, further aggravated by the OSA-associated
      hormonometabolic alterations, such as insulin resistance, dyslipidemia, and
      adipokine imbalance. As shown in OSA patients and in the animal model, genetic
      susceptibility, comorbidities (obesity), and life habits (high fat diet) may
      aggravate atherosclerosis development or progression. The intimate molecular
      mechanisms are still largely unknown, and their understanding may contribute to
      delineate new targets for prevention strategies and/or development of new
      treatment of OSA-related atherosclerosis, especially in patients at risk for
      cardiovascular disease.

PMID- 19404650
TI  - Heterotopic salivary gland presenting as a supra-clavicular swelling.
AB  - A 5-month-old female was referred to the paediatric surgery clinic with a neck
      swelling in the right supra-clavicular region. This was thought clinically to be
      cystic hygroma. Pathology showed an ectopic salivary gland. This should be added
      to the list of differential diagnoses of neck swelling in childhood.

PMID- 19404649
TI  - Long-term outcome of asymptomatic patients with congenital cystic adenomatoid
      malformation.
AB  - PURPOSE: Congenital cystic adenomatoid malformation (CCAM) represents a rare
      congenital anomaly of the lung. It remains controversial whether patients with
      asymptomatic lesions warrant early surgical intervention. Our aim was to review
      the outcome of asymptomatic CCAM patients at a paediatric tertiary centre.
      METHODS: The medical case notes of all children with CCAM presenting to our
      institution between 1986 and 2007 were reviewed. Data on pre- and post-natal
      investigations, clinical presentation, lesion site, type of surgical procedure,
      timing, and outcomes of surgery were reviewed. RESULTS: A total of 35 patients
      were diagnosed with CCAM during the 21-year study period (1986-2007). Sixty
      percent (n = 21) were asymptomatic at birth including eight patients with
      prenatal ultrasound scan confirming CCAM. In this group, 18 patients (86%)
      subsequently developed symptoms (median age 2 years, range 1 month-13 years) and
      required surgery. Symptoms included pneumonia with or without infected CCAM
      (43%), respiratory distress (14%) and spontaneous pneumothorax (14%). Eight
      patients underwent multiple hospital presentations with complications related to
      CCAM. Of the 21 initially asymptomatic patients, 17 (81%) underwent surgical
      resection. Only one of these patients was completely asymptomatic prior to
      surgery. There were eight post-operative complications and no mortality. One
      patient underwent a second thoracotomy for residual CCAM. The median length of
      hospital stay was 9 days (range 3-32 days). CONCLUSION: This study suggests
      patients who present with asymptomatic CCAM will subsequently become symptomatic.
      Early surgical referral and intervention may be beneficial to avoid the
      development of complications.

PMID- 19404651
TI  - Clear cell colorectal carcinoma: a case report with analysis of neo-angiogenesis.

PMID- 19404652
TI  - Pathology and new players in the pathogenesis of brain edema.
AB  - Brain edema continues to be a major cause of mortality after diverse types of
      brain pathologies such as major cerebral infarcts, hemorrhages, trauma,
      infections and tumors. The classification of edema into vasogenic, cytotoxic,
      hydrocephalic and osmotic has stood the test of time although it is recognized
      that in most clinical situations there is a combination of different types of
      edema during the course of the disease. Basic information about the types of
      edema is provided for better understanding of the expression pattern of some of
      the newer molecules implicated in the pathogenesis of brain edema. These
      molecules include the aquaporins, matrix metalloproteinases and growth factors
      such as vascular endothelial growth factors A and B and the angiopoietins. The
      potential of these agents in the treatment of edema is discussed. Since many
      molecules are involved in the pathogenesis of brain edema, effective treatment
      cannot be achieved by a single agent but will require the administration of a
      "magic bullet" containing a variety of agents released at different times during
      the course of edema in order to be successful.

PMID- 19404653
TI  - Absence of alpha-synuclein pathology in postencephalitic parkinsonism.
AB  - Postencephalitic parkinsonism (PEP), a chronic complication of encephalitis
      lethargica, is a tauopathy characterized by multisystem neuronal loss and gliosis
      with widespread neurofibrillary lesions composed of both 3- and 4-repeat (3R and
      4R) tau isoforms. Previous immunohistochemical studies in a small number of PEP
      cases demonstrated absence of Lewy bodies as well as the lack of other alpha
      synuclein pathology, classifying PEP as a "pure" tauopathy. Neuropathologic
      examination of 10 brains with clinico-pathologically verified PEP confirmed
      widespread neurodegeneration in subcortical and brainstem areas associated with
      multifocal neurofibrillary pathology comprising both 3R and 4R tau. Very rare
      beta-amyloid deposits were observed in two elderly patients, while Lewy bodies
      and neurites or any other alpha-synuclein deposits were completely absent. The
      causes and molecular background of total absence of alpha-synuclein pathology in
      PEP, in contrast to most other tauopathies, remain as unknown as the pathogenesis
      of PEP.

PMID- 19404654
TI  - Percutaneous suturing of the ruptured Achilles tendon with endoscopic control.
AB  - INTRODUCTION: A prospective study of modified percutaneous Achilles tendon repair
      performed between 1999 and 2005 under local infiltration anesthesia is presented;
      the study evaluated the results of percutaneous repair technique by visualization
      of the synovia under endoscopic control, followed by early functional
      postoperative treatment for surgical intervention of acute Achilles tendon
      ruptures. PATIENTS: Sixty-two patients (58 males, 4 females, mean age 32) were
      treated by percutaneous suturing with modified Bunnel technique under endoscopic
      control within 10 days after acute total rupture. Physiotherapy was initiated
      immediately after the operation and patients were encouraged to weight-bearing
      ambulation with a walking brace-moon boot as tolerated. Full weight-bearing was
      allowed minimum after 3 weeks postoperatively without brace. RESULTS: The
      procedure was tolerated in all patients. There were no significant ROM limitation
      was observed. Two patients experienced transient hypoesthesia in the region of
      sural nerve that spontaneously resolved in 6 months. Fifty-nine patients (95%)
      including professional athletes returned to their previous sportive activities,
      while 18 of them (29%) had some minor complaints. The interval from injury to
      return to regular work and rehabilitation training was 11.7 weeks (10-13 weeks).
      At the latest follow-up (mean: 46 months; range: 12-78 months), all the patients
      had satisfactory results with a mean American Orthopedic Foot and Ankle Society's
      ankle-hindfoot score of 94.6. No re-ruptures, deep venous thrombosis or wound
      problems occurred. CONCLUSION: The proposed method offers a reasonable treatment
      option for acute total Achilles tendon rupture with a low number of
      complications. The rerupture rate and return to preinjury activities are
      comparable to open and percutaneous without endoscopic control procedures.

PMID- 19404656
TI  - Prospective randomized trial of TVT and TOT as primary treatment for female
      stress urinary incontinence with or without pelvic organ prolapse in Southeast
      China.
AB  - OBJECTIVE: To compare the outcomes of tension- free vaginal tape (TVT) and
      transobturator tape (TOT) in the treatment of female stress urinary incontinence
      with or without concomitant pelvic organ prolapse (POP). METHODS: One hundred and
      forty patients with SUI were randomly allocated to TVT (n=70) or TOT (n=70). The
      objective outcomes were assessed with a stress test, 1-h pad test. Subjective
      outcomes were assessed with UDI-6/(IIQ-7) questionnaires. RESULTS: The surgical
      outcomes revealed no significant difference between TVT and TOT surgical route.
      Both the subjective and objective cure rates were 91.4% in the TOT group, while
      90 and 92.8% in the TVT group, respectively. The results showed the association
      to pelvic floor surgical techniques did not diminish a year later. TOT procedure
      has a shorter operative time for patients without concomitant surgery.
      CONCLUSION: The efficacy and safety of TVT procedure were similar to that of TOT
      procedure for female stress urinary incontinence with or without concomitant POP.

PMID- 19404655
TI  - Mammotome versus ATEC: a comparison of two breast vacuum biopsy techniques under
      sonographic guidance.
AB  - PURPOSE: The study evaluates the differences between the Mammotome (MT) and ATEC
      (A) vacuum biopsy (VB) of the breast in terms of diagnostic reliability, biopsy
      duration and complications. METHODS: In a prospective randomized study, 62
      ultrasound-guided VBs of the breast were performed. MT and A were compared using
      Mann-Whitney U test. RESULTS: The mean lesion size and the BI-RADS distribution
      were equal in both groups. Representative tissue was extracted in all 62
      biopsies; thus no repeat biopsies were necessary. A sonographically guided
      complete excision was possible in 46 cases. More imaging-guided complete
      excisions were achieved with the MT than with A (87 vs. 63%). Technical
      complications occurred twice with A and once with MT. No medical complications
      occurred in either group. CONCLUSIONS: Both systems are suitable for the
      diagnostic clarification of unclear breast lesions as well as complete excision
      of benign lesions under sonographic imaging. Sonographically guided complete
      resection was achieved more often with the MT.

PMID- 19404657
TI  - Knowledge, attitude and practices of contraception in urban population of North
      India.
AB  - BACKGROUND: Despite the provision of safe and affordable family planning
      services, 120 million couples worldwide are not using any contraception to limit
      or space their family, and many who use one or the other method, conceive.
      According to the National Population Policy (NPP) 2000, various methods of
      contraception and fertility regulation shall be made accessible to all, so that
      India's population in 2010 will be 1,107 million instead of 1,162 million.
      MATERIALS AND METHODS: A hospital-based cross-sectional survey conducted in 2006.
      In-person interviews carried out with attendees of Gynaecology and Obstetrics
      outpatient clinics, and indoor patients of three hospitals of urban population to
      collect data regarding knowledge, attitude and practices of family planning
      methods. RESULTS: A total of 55.2% subjects were aware of contraceptive methods,
      mostly barrier (52.7%), IUCD (46.1%) and oral pills (43.2%), but only 31.7% had
      ever used barrier contraception, IUCD 10.3% and oral pills 3.3%. Permanent
      methods were known to nearly 50% subjects but acceptance was very less, 5% only.
      Emergency contraception was known to 13.8% subjects. CONCLUSION: Majority of
      women have favorable attitude towards family planning, but use of long-acting new
      methods is still low in our population, which needs to be promoted.

PMID- 19404658
TI  - Can sonographic endometrial pattern be an early indicator for tubal ectopic
      pregnancy and related tubal rupture?
AB  - PURPOSE: The present study aims to determine whether sonographic endometrial
      pattern can be addressed as an early indicator for tubal ectopic pregnancy and
      related tubal rupture in case ultrasonography reveals no adnexal mass and
      maternal serum beta human chorionic gonadotropin (HCG) level is below the
      discriminatory zone (<or=1,000 mIU/mL). METHODS: The study evaluated the
      endometrial features of 441 naturally conceived and asymptomatic first trimester
      (99 tubal ectopic, 138 failing and 264 normal intrauterine) with maternal serum
      beta HCG levels<or=1,000 mIU/mL and indeterminate sonographic findings. RESULTS:
      Tubal ectopic, failing intrauterine and normal intrauterine pregnancies are
      statistically similar in aspect of endometrial thickness. However, trilaminar
      endometrial pattern was significantly less frequent in failing and normal
      intrauterine pregnancies but significantly more frequent in ruptured tubal
      pregnancies. Also the relative risk of tubal rupture is significantly higher in
      case of trilaminar endometrial pattern. Trilaminar endometrial pattern has a
      sensitivity of 21.2%, specificity of 93.9%, positive predictive value of 50.0%
      and negative predictive value of 80.5% for distinguishing tubal ectopic
      pregnancy. Moreover, the sensitivity, specificity, positive and negative
      predictive values of the same pattern are computed to be 60.0, 95.7, 85.7 and
      84.6%, respectively, in the prediction of ruptured tubal pregnancy. CONCLUSIONS:
      Sonographic appearance of endometrium may be used to predict tubal pregnancy when
      ultrasonography shows no adnexal mass and maternal serum HCG<or=1,000 mIU/mL.
      That is, trilaminar pattern may indicate tubal pregnancy and warn about a
      possible related rupture in case of previous ectopic pregnancy or pelvic surgery.

PMID- 19404659
TI  - Do asymptomatic patients require routine hemoglobin testing following uneventful,
      unplanned cesarean sections?
AB  - OBJECTIVE: To determine the clinical usefulness of routine postoperative
      hemoglobin testing after unplanned, uneventful cesarean sections in low-risk
      women without any signs or symptoms of anemia and to identify possible risk
      factors for hemorrhage. MATERIALS AND METHODS: Retrospective analysis of the
      charts of all women who underwent non-elective and uneventful cesarean section
      over 12 months was performed and demographic data, estimated blood loss at
      surgery, pre- and post-operative hemoglobin values, postoperative symptoms
      suggesting anemia, and incidence of transfusion were tabulated. Statistical
      analysis was done with Student t test and Mann-Whitney U test. RESULTS: A total
      of 2,450 women were delivered during the study period among whom 743 of them
      (30.3%) underwent cesarean section. Among the cesarean sections, 421 (56.6%) were
      found to be unplanned and uneventful operations performed in low-risk women with
      no postoperative signs or symptoms for anemia. The mean preoperative hemoglobin
      of the low-risk asymptomatic women was 11.7+/-1.99 g/dl, whereas it was 11.24+/
      1.99 g/dl, postoperatively (P<0.001). In 72% of the patients, there was a drop in
      hemoglobin concentrations, whereas 24.5% experienced an increase and 3.5% showed
      no change, postoperatively. Only one woman experienced a drop of greater than 30%
      in hemoglobin concentration. Since the woman did not show any signs of
      hemodynamic instability or symptoms of anemia, she was not transfused.
      CONCLUSION: Our findings suggest that routine hemoglobin testing following
      uneventful, unplanned cesarean section neither change postoperative management
      nor determine the patients requiring blood transfusion.

PMID- 19404660
TI  - Cajal's contribution to the knowledge of the neuronal cell nucleus.
AB  - In 1906, the Spanish neurobiologist Santiago Ramon y Cajal was awarded the Nobel
      Prize in Physiology or Medicine in recognition of his work on the structure of
      neurons and their connections. Cajal is commonly regarded as the father of modern
      neuroscience. What is less well known is that Cajal also had a great interest in
      intracellular neuronal structures and developed the reduced silver nitrate method
      for the study of neurofibrils (neurofilaments) and nuclear subcompartments. It
      was in 1903 that Cajal discovered the "accessory body" ("Cajal body") and seven
      years later, published an article on the organization of the cell nucleus in
      mammalian neurons that represents a masterpiece of nuclear structure at the light
      microscopy level. In addition to the accessory body, it includes the analysis of
      several nuclear components currently recognized as fibrillar centers of the
      nucleolus, nuclear speckles of splicing factors, transcription foci, nuclear
      matrix, and the double nuclear membrane. The aim of this article is to revisit
      Cajal's contributions to the knowledge of the neuronal nucleus in light of our
      current understanding of nuclear structure and function.

PMID- 19404662
TI  - Comparison of central corneal thickness and anterior chamber depth measurements
      using three imaging technologies in normal eyes and after phakic intraocular lens
      implantation.
AB  - BACKGROUND: The repeatability and interchangeability of imaging devices measuring
      central corneal thickness (CCT) and anterior chamber depth (ACD) are important in
      the assessment of patients considering refractive surgery. The purpose of this
      study was to investigate the agreement of CCT and ACD measurements using three
      imaging technologies in healthy eyes and in eyes after phakic intraocular lens
      implantation (pIOL). METHODS: In this comparative study, CCT and ACD were
      measured using anterior segment optical coherence tomography (AS-OCT), Orbscan
      II, and Pentacam in 33 healthy volunteers (66 eyes) and 22 patients (42 eyes)
      after pIOL implantation. Intraobserver repeatability was evaluated for all three
      devices in the healthy volunteer group. RESULTS: Pairwise comparison of CCT
      measurements showed significant differences between all devices (P < 0.001),
      except for the AS-OCT and Orbscan II in the healthy volunteer group (P = 0.422)
      and the Orbscan II and Pentacam in the pIOL group (P = 0.214). ACD measurements
      demonstrated significant differences between all pairwise comparisons in both
      groups (P < or = 0.001). Intraobserver reliability was high for CCT and ACD
      measurements in the healthy volunteer group, with coefficients of variation
      ranging from 0.6% to 1.2% and 0.4% to 0.5% respectively. CONCLUSIONS: CCT and ACD
      measurements using AS-OCT, Orbscan II, and Pentacam demonstrated high
      intraobserver reliability. However, these devices should not be used
      interchangeably for measurements of CCT and ACD in healthy subject and patients
      after pIOL implantation.

PMID- 19404661
TI  - Intravitreal ranibizumab (Lucentis) in the treatment of retinal angiomatous
      proliferation (RAP).
AB  - BACKGROUND: Retinal angiomatous proliferation (RAP) is a distinct variant of
      neovascular age-related macular degeneration (AMD). The aim of this study is to
      evaluate the functional and anatomic outcome after intravitreal ranibizumab
      (Lucentis) treatment in patients with RAP. METHODS: Prospective study of
      consecutive patients with newly diagnosed or recurrent RAP treated with
      intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and
      December 2007. Baseline and monthly follow-up visits included best-corrected
      visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein
      and indocyanine green angiography were performed at baseline and repeated at
      least every 3 months. RESULTS: Thirty-one eyes of 31 patients were treated with
      0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007.
      The mean age of the patients was 82.6 years (SD:4.9). The mean number of
      intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to
      12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline
      mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR
      BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD:
      0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7
      lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 microm, and
      decreased significantly to a mean of 224 microm (P < 0.001) at the last follow
      up. Mean reduction of CMT was 152 microm (SD: 58). An average of 81.5% of the
      total visual improvement and 85% of the total CMT reduction occurred during the
      first post-operative month after one intravitreal injection of ranibizumab.
      During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No
      injection complications or systemic drug-related side-effects were noted during
      the follow-up period. CONCLUSIONS: Intravitreal ranibizumab injections appeared
      to be an effective and safe treatment for RAP, resulting in visual gain and
      reduction in macular thickness. Further long-term studies to evaluate the
      efficacy of intravitreal ranibizumab in RAP are warranted.

PMID- 19404663
TI  - Change in ocular alignment after topical anesthetic cataract surgery.
AB  - BACKGROUND: To report the incidence of, and change in ocular misalignment
      following topical anesthetic cataract surgery. METHODS: Prospectively, 160
      consecutive patients who were scheduled for cataract surgery under topical
      anesthesia were evaluated. All patients had a complete ophthalmic examination,
      including ocular alignment evaluation, just before and 1 day, 1 week, 3 weeks,
      and 2 months after cataract surgery. RESULTS: Preoperatively, 26 patients had
      ocular misalignment. Mean deviation in these preexisting misalignment was 7.2 +/-
      6.8 prism diopters (PD). Postoperatively, the angle of deviation improved to 5.4
      +/- 7.4 PD. Acquired ocular misalignment after cataract surgery occurred in 12 of
      160 patients (8%) at 1 day, and seven of 131 (5%) at 2 months. None of these
      seven patients sought medical attention for the diplopia. CONCLUSIONS: The
      overall incidence of topical anesthesia-related change in ocular alignment after
      uneventful cataract surgery was 5%. However, no patients had symptomatic
      diplopia. Topical anesthetic cataract surgery could abolish the risk of
      postoperative diplopia and improve the heterophoric status of preexisting
      misalignment.

PMID- 19404664
TI  - Kestenbaum procedure on the vertical rectus muscles with simultaneous
      compensation of the induced cyclodeviation for nystagmus patients with chin-up or
      chin-down head posture.
AB  - BACKGROUND: Kestenbaum surgery is performed for nystagmus-related abnormal head
      posture, and symmetrically changes the position of both eyes to shift the null
      point to the primary position. Most patients with infantile nystagmus have their
      null point zone in a lateral gaze position. Less frequently, surgery can be
      performed to reduce chin-up or chin-down head posture. We report indications for,
      and the results of eight consecutive interventions performed according to the
      Kestenbaum principle for the reduction of a chin-up or chin-down head posture.
      METHODS: In a retrospective study, the clinical findings for eight patients who
      consecutively underwent treatment in the University Eye Hospital of Cologne
      between 2001 and 2007 were investigated. The patients were aged 6 to 16 years;
      median age was 6.5 years. For all patients, surgery was to correct a chin-up or
      chin-down head posture due to infantile nystagmus. Preoperatively, five patients
      showed a chin-down, three a chin-up head posture. All vertical rectus muscles
      were recessed or tucked between 6 and 7 mm; the resulting cyclodeviation was
      reduced by an intervention on the superior oblique muscles (6 to 8 mm tucking, in
      the case of chin-down, or recession in the case of chin-up head posture).
      RESULTS: Surgery was successful in seven of the eight patients, with a reduction
      of the vertical head posture to less than 10 degrees. In the cases of chin-down
      posture, head posture was reduced to between 0 degrees and a maximum of 20
      degrees in one case postoperatively (before the operation 20 degrees to 35
      degrees ); in the cases of chin-up posture, to less than 8 degrees (before the
      operation 25 degrees to 35 degrees). One case showed no postoperative improvement
      in chin-down posture but a head turn to the left of up to 20 degrees; another
      case had a remaining chin-up posture of 8 degrees with a right turn of 15 degrees
      . Binocular vision was better or the same in all cases after surgery. CONCLUSION:
      For nystagmus patients with chin-up or chin-down head posture, surgery for
      bilateral parallel shifting of the eyes can considerably improve the head
      posture. It is possible to compensate the induced cyclodeviation at the same time
      by bilateral surgery on the superior oblique muscles.

PMID- 19404665
TI  - Changes in neovascular choroidal morphology after intravitreal bevacizumab
      injection: prospective trial on 156 eyes throughout 12-month follow-up.
AB  - BACKGROUND: To report 12-month follow-up results of 156 eyes treated with anti
      VEGF for subfoveal choroidal neovascularization (CNV) secondary to age-related
      macular degeneration, and to verify the efficacy of this treatment in terms of
      functional results and changes of morphology of choroidal membrane for the
      different types of choroidal neovascularization analyzed. METHODS: This
      prospective case series study included subjects with different forms of subfoveal
      CNV. After the first intravitreal injection of 1.25 mg bevacizumab at baseline,
      re-injections of bevacizumab were scheduled at least 4 weeks after initial
      treatment following standardized criteria. RESULTS: One hundred and fifty six
      patients were divided into two study groups: 60 eyes with classic CNV (group C)
      and 96 eyes with occult CNV (group O). The improvement in BCVA was greater in
      group C than group O, although the difference was not statistically significant
      (P = 0.26). The area of CNV and subretinal fibrous tissue/disciform scar remained
      stable over time in both groups. The macular thickness significantly decreased
      through the follow-up period in both groups. The hyper-reflective area of the
      neovascular complex remained stable in both groups during the first 6 months of
      follow-up, whereas a slight increase of hyper-reflective lesion size occurred
      throughout the second 6 months of follow-up. CONCLUSION: The CNV lesion treated
      with IVB didn't disappear in neither group, but showed less exudation,
      demonstrated by a decrease in the area of leakage from CNV, subretinal fluid
      area, and centre point retinal thickness on OCT.

PMID- 19404666
TI  - Diabetic patients with retinopathy show increased retinal venous oxygen
      saturation.
AB  - BACKGROUND: Longstanding diabetes mellitus results in a disturbed
      microcirculation. A new imaging oximeter was used to investigate the effect of
      this disturbance on retinal vessel oxygen saturation. METHODS: The haemoglobin
      oxygen saturation was measured in the retinal arterioles and venules of 41
      diabetic patients (65 +/- 12.3 years) with mild non-proliferative through
      proliferative diabetic retinopathy (DR). Twelve individuals (61.3 +/- 6.2 years,
      mean +/- standard deviation) without systemic or ocular disease were investigated
      as controls. Measurements were taken by an imaging oximeter (oxygen module by
      Imedos GmbH, Jena). This technique is based on the proportionality of the oxygen
      saturation and ratio of the optical density of the vessel at two wavelengths (548
      nm and 610 nm). RESULTS: Whereas there were no significant differences in the
      arterial oxygen saturation between controls and diabetic retinopathy at any
      stage, the venous oxygen saturation increased in diabetic patients with the
      severity of the retinopathy: controls 63 +/- 5%, mild non-proliferative DR 69 +/-
      7%, moderate non-proliferative DR 70 +/- 5%, severe non-proliferative DR, 75 +/-
      5%, and proliferative DR 75 +/- 8%. CONCLUSIONS: The increase of retinal vessel
      oxygen saturation in diabetic retinopathy points to a diabetic microvascular
      alteration. This may be due to occlusions and obliterations in the capillary bead
      and the formation of arterio-venous shunt vessels. On the other hand,
      hyperglycaemia-induced endothelial dysfunction, with subsequent suppression of
      the endothelial NO-synthase and disturbance of the vascular auto-regulation, may
      contribute to retinal tissue hypoxia.

PMID- 19404667
TI  - Human signal peptide had advantage over mouse in secretory expression.
AB  - The signal peptide is a critical component in the secretory expression of protein
      in eukaryotic cells. It has been verified that the signal peptide of mouse nerve
      growth factor could mediate the secretory expression of beta-endorphin in
      cultured non-neuronal cells. Although there is a counterpart of nerve growth
      factor in human genome, no research about the signal sequence from human genome
      has been reported. The function of mediating secretory expression is affected by
      many factors. We assumed that the counterpart from human genome could function as
      the signal peptide from mouse nerve growth factor does and these two signal
      sequences had different efficiency in mediating secretory expression of beta
      endorphin, but we could not figure out which one had a better function. To
      validate our hypothesis and give an answer to the question, we constructed two
      eukaryotic vectors, pcDNA3.1-hEP and pcDNA3.1-mEP, containing human and mouse
      signal sequences in fusion genes, respectively. RT-PCR showed that the
      constructed fusion genes were expressed in NIH3T3 cells. We also found that the
      detected beta-endorphin by the immunofluorescent technique was mainly in the
      cytoplasm of NIH3T3 cells. The concentration of beta-endorphin in the culture
      medium by RIA is 280.33 +/- 24.16 (pg/ml) and 191.04 +/- 7.96 (pg/ml) from
      pcDNA3.1-hEP and pcDNA3.1-mEP, respectively, and there was a significant
      statistical difference between them (P < 0.05). A difference existed between them
      and that from blank vector individually (P < 0.01). These findings suggest that
      our constructed fusion gene containing the signal sequence of human nerve growth
      factor can be secretorily expressed and the efficiency of the signal peptide from
      human nerve growth factor is higher than that of mouse signal peptide.

PMID- 19404668
TI  - Protein phosphatase 1A (PPM1A) is involved in human cytotrophoblast cell invasion
      and migration.
AB  - Trophoblast invasion is crucial for embryo implantation and placentation.
      Excessive trophoblast invasion leads to hydatidiform moles and choriocarcinoma.
      PPM1A is a phosphatase which dephosphorylates and inactivates a broad range of
      substrates, including TGF-beta, MAP kinases, p38 and JNK kinase cascades, and is
      involved in tumor suppression. The objective of this study was to investigate the
      expression of PPM1A in normal and malignant human placenta and its role in
      trophoblast invasion, which shares many similarities with invasion of tumor
      cells. By Western blotting and immunocytochemistry, significantly higher
      expression of PPM1A in human placental villi at term was found as compared with
      that during the first trimester. Furthermore, the expression level of PPM1A
      protein in hydatidiform moles was lower compared with that during normal
      pregnancy. We further investigated the function of PPM1A in extravillous
      trophoblast cell line HTR8/SVneo. Transwell migration and Matrigel invasion
      assays demonstrated that PPM1A siRNA significantly promoted the motility and
      invasiveness of the cells. Gelatin zymography showed that knockdown of PPM1A with
      siRNA elevated the expression of pro-matrix metalloproteinase pro-(MMP)-9, but
      down-regulated tissue inhibitors of metalloproteinases (TIMP)-2. The present data
      indicate that PPM1A plays a critical role in the regulation of normal
      placentation by inhibiting trophoblast migration and invasion.

PMID- 19404669
TI  - The elevated expression of calcitonin receptor by cells recruited into the
      endothelial layer and neo-intima of atherosclerotic plaque.
AB  - Calcitonin receptor-immunoreactive (CTR-ir) endothelial and foam cells were
      identified in atherosclerotic plaque within the abdominal and thoracic aortas of
      rabbits fed a cholesterol-supplemented diet. Initially, cells within the
      endothelial layers of nascent atherosclerotic plaque of arteries were also CD34
      positive, a marker of precursor cells of the haematopoietic lineage. In a further
      rabbit model with more advanced cardiovascular disease, CTR-ir cells were located
      deeper within the plaque as well as within the endothelial layer overlying the
      neo-intima. Finally, in the third model, in which the 4-week period on the
      atherogenic diet was followed by a 12-week period of regression on a normal chow
      diet, during which serum cholesterol levels returned to the normal range, CTR-ir
      was markedly reduced in the stabilized fibrous cap of plaque. Thus, the
      expression of CTR is associated with the early cellular events involved in plaque
      formation and is down-regulated as stabilisation of plaque progresses in the
      process of healing.

PMID- 19404670
TI  - Normalized EMG to normalized torque relationship of vastus intermedius muscle
      during isometric knee extension.
AB  - The purpose of the present study was to investigate the electromyography (EMG) to
      torque relationship of the vastus intermedius (VI) muscle. Thirteen healthy men
      performed maximal voluntary contraction (MVC) and submaximal contraction during
      isometric knee extension at 10% of the MVC to 90% of the MVC at intervals of 10%
      of the MVC level. Surface EMG was detected from four muscle components of the QF
      muscle group, i.e., VI, vastus lateralis (VL), vastus medialis, and rectus
      femoris (RF) muscles. Normalized muscle activation in the VI muscle was
      significantly lower than in the VL muscle at a lower torque level (20 and 40% of
      MVC) and significantly lower compared to the RF muscle at a higher torque level
      (from 60 to 90% of MVC). These results suggest that neuromuscular activation in
      the VI muscle is not consistent with the other components of QF muscle group
      during submaximal knee extension contractions.

PMID- 19404671
TI  - Effects of exercise training on the matrix metalloprotease response to acute
      exercise.
AB  - Matrix metalloproteases (MMPs) in the circulation are thought to modulate the
      activation of growth factors, cytokines, and angiogenesis, facilitating
      physiological adaptations to exercise training. The purpose of this work was to
      characterize serum MMP-1, MMP-2, MMP-3, and MMP-9 concentrations pre- and post
      eight weeks of exercise training. We tested the hypothesis that exercise training
      would influence serum MMP concentrations in response to an acute resistance
      exercise test (ARET). Participants were randomized into an 8-week training
      program (5 days per week) that emphasized callisthenic (CT, N = 8) or resistance
      (RT, N = 8) exercise. Serum MMP concentrations (MMP-1, -2, -3, -9) were assessed
      in men (N = 16) in response to an acute bout of high-intensity resistance
      exercise (six sets of 10-RM squats with 2-min inter-set rest periods) both before
      and after 8 weeks of training. Training resulted in a temporal shift in the peak
      MMP-1 concentration from post-ARET to mid-ARET in both groups. Post-training, MMP
      9 concentrations were increased immediately after the ARET in the CT group as
      compared to pre-training ARET concentrations. RT did not alter MMP-3 and -9
      concentrations. These data suggest that the mode of exercise training influences
      the MMP response to an acute bout of exercise, revealing a possible role of MMPs
      in initiating training-specific adaptations.

PMID- 19404672
TI  - Fatigue resistance during high-intensity intermittent exercise from childhood to
      adulthood in males and females.
AB  - This study examined the maturation pattern of fatigue resistance (FR) from
      childhood to adulthood in females and males during high-intensity intermittent
      exercise and compared FR between females and males in childhood and adolescence.
      Thirty males (boys 11.3 +/- 0.5 years, teen-males 14.7 +/- 0.3 years, men 24.0 +/
      2.1 years) and 30 females (girls 10.9 +/- 0.6 years, teen-females 14.4 +/- 0.7
      years, women 25.2 +/- 1.4) participated in this study. They performed high
      intensity intermittent exercise (4 x 18 maximal knee flexions and extensions with
      1-min rest) on an isokinetic dynamometer at 120 degrees s(-1). Peak torque of
      flexors (PTFL) and extensors (PTEX), and total work (TW) were measured. FR was
      calculated as % of PTEX, PTFL, and TW in 4th versus 1st set. FR was greater (P <
      0.05) in boys versus teen-males and men, and in teen-males versus men. In
      females, FR was greater (P < 0.05) in girls versus teen-females and women, but
      not different between teen-females and women. FR was not different in boys versus
      girls and in teen-males versus teen-females. FR for PTFL, PTEX, and TW correlated
      negatively (P < 0.001) with the respective peak values (r = -0.68 to -0.84), and
      FR for TW with peak lactate (r = -0.58 to -0.69). In addition, age correlated (P
      < 0.01) with FR for males (r = -0.75) and females (r = -0.55). In conclusion, FR
      during high-intensity intermittent exercise undergoes a gradual decline from
      childhood to adulthood in males, while in females the adult profile establishes
      at mid-puberty (14-15 years). The maturation profile of FR in males and females
      during development appears to reflect the maturation profiles of peak torque,
      short-term muscle power, and lactate concentration after exercise.

PMID- 19404673
TI  - Totally laparoscopic pancreaticoduodenectomy for locally advanced gastric cancer.
AB  - BACKGROUND: In patients having locally advanced cancer of the stomach with
      suspected tumor infiltration to the pancreatic head or the duodenum, a concurrent
      pancreaticoduodenectomy with gastrectomy is occasionally prerequisite to achieve
      a microscopically tumor-free surgical margin. MATERIALS AND METHODS: We present
      the first series of successful totally laparoscopic pancreaticoduodenectomy
      (TLPD) for advanced gastric cancer with suspected infiltration to the pancreatic
      head. RESULTS: TLPD was successfully performed without adverse events during
      surgery and resulted in favorable short-term outcomes of three patients with
      locally advanced gastric cancer with suspected invasion to the pancreas.
      CONCLUSIONS: Although TLPD for locally advanced gastric cancer is a technically
      difficult challenging operation that requires careful dissection along the major
      vessels, intracorporeal tie sutures, and the placement of an external drainage
      tube into a narrow pancreatic duct, this procedure is technically feasible and
      safe in the hands of experienced surgeons. Long-term follow-up is mandatory to
      validate oncological outcome.

PMID- 19404674
TI  - Angiotensin II type 1 receptor mediates partially hyposmotic-induced increase of
      I (Ks) current in guinea pig atrium.
AB  - A repolarizing conduction in the heart augmented by hyposmotic or mechanically
      induced membrane stretch is the slow component of delayed rectifier K(+) current
      (I (Ks)). I (Ks) upregulation is recognized as a factor promoting appearance of
      atrial fibrillation (AF) since gain-of-function mutations of the channel genes
      have been detected in congenital AF. Mechanical stretch activates angiotensin II
      type 1 (AT(1)) receptor in the absence of its physiological ligand angiotensin
      II. We investigated the functional role of AT(1) receptor in I (Ks) enhancement
      in hyposmotically challenged guinea pig atrial myocytes using the whole-cell
      patch-clamp method. In atrial myocytes exposed to hyposmotic solution with
      osmolality decreased to 70% of the physiological level, I (Ks) was enhanced by
      84.1%, the duration of action potential at 90% repolarization (APD(90)) was
      decreased by 16.8%, and resting membrane potential was depolarized (+4.9 mV). The
      hyposmotic-induced effects on I (Ks) and APD(90) were significantly attenuated by
      specific AT(1) receptor antagonist candesartan (1 and 5 muM). Pretreatment of
      atrial myocytes with protein tyrosine kinase inhibitors tyrphostin A23 and A25
      suppressed but the presence of tyrosine phosphatase inhibitor orthovanadate
      augmented hyposmotic stimulation of I (Ks). The above results implicate AT(1)
      receptor and tyrosine kinases in the hyposmotic modulation of atrial I (Ks) and
      suggest acute antiarrhythmic properties of AT(1) antagonists in the settings of
      stretch-related atrial tachyarrhythmias.

PMID- 19404675
TI  - A novel insight into the regulation of light-independent chlorophyll biosynthesis
      in Larix decidua and Picea abies seedlings.
AB  - Light-independent chlorophyll (Chl) biosynthesis is a prerequisite for the
      assembly of photosynthetic pigment-protein complexes in the dark. Dark-grown
      Larix decidua Mill. seedlings synthesize Chl only in the early developmental
      stages and their Chl level rapidly declines during the subsequent development.
      Our analysis of the key regulatory steps in Chl biosynthesis revealed that
      etiolation of initially green dark-grown larch cotyledons is connected with
      decreasing content of glutamyl-tRNA reductase and reduced 5-aminolevulinic acid
      synthesizing capacity. The level of the Chl precursor protochlorophyllide also
      declined in the developing larch cotyledons. Although the genes chlL, chlN and
      chlB encoding subunits of the light-independent protochlorophyllide
      oxidoreductase were constitutively expressed in the larch seedlings, the
      accumulation of the ChlB subunit was developmentally regulated and ChlB content
      decreased in the fully developed cotyledons. The efficiency of chlB RNA-editing
      was also reduced in the mature dark-grown larch seedlings. In contrast to larch,
      dark-grown seedlings of Picea abies (L.) Karst. accumulate Chl throughout their
      whole development and show a different control of ChlB expression. Analysis of
      the plastid ultrastructure, photosynthetic proteins by Western blotting and
      photosynthetic parameters by gas exchange and Chl fluorescence measurements
      provide additional experimental proofs for differences between dark and light Chl
      biosynthesis in spruce and larch seedlings.

PMID- 19404676
TI  - Effects of MULTIFOLIATE-PINNA, AFILA, TENDRIL-LESS and UNIFOLIATA genes on
      leafblade architecture in Pisum sativum.
AB  - In order to dissect the genetic regulation of leafblade morphogenesis, 16
      genotypes of pea, constructed by combining the wild-type and mutant alleles of
      MFP, AF, TL and UNI genes, were quantitatively phenotyped. The morphological
      features of the three domains of leafblades of four genotypes, unknown earlier,
      were described. All the genotypes were found to differ in leafblade morphology.
      It was evident that MFP and TL functions acted as repressor of pinna
      ramification, in the distal domain. These functions, with and without interaction
      with UNI, also repressed the ramification of proximal pinnae in the absence of AF
      function. The expression of MFP and TL required UNI function. AF function was
      found to control leafblade architecture multifariously. The earlier identified
      role of AF as a repressor of UNI in the proximal domain was confirmed. Negative
      control of AF on the UNI-dependent pinna ramification in the distal domain was
      revealed. It was found that AF establishes a boundary between proximal and distal
      domains and activates formation of leaflet pinnae in the proximal domain.

PMID- 19404678
TI  - Giardiasis in kindergartens: prevalence study in Berlin, Germany, 2006.
AB  - In Germany, an increase of notified giardiasis was observed between 2002 (n =
      3,101) and 2007 (n = 3,651) with 62% of cases acquired in Germany. The highest
      incidence was reported in 1- to 5-year-olds (2001-2007, 11.5/100,000 on average)
      and Berlin is one of the most affected states (17.5/100,000). We performed a
      cross-sectional study in five Berlin kindergartens differing in socioeconomic
      status and migrant proportion in order to estimate the prevalence and investigate
      routes of transmission among children under 6 years of age. Stool samples were
      screened for Giardia lamblia and Cryptosporidium parvum using microscopical and
      antigen detection. Giardia-positive samples underwent PCR and subtyping. Two
      hundred two children participated (mean age 3.4 years). We found three girls
      (1.5%) who tested positive for G. lamblia genotype-A3, all clustering in one
      kindergarten (prevalence 5.5%). No common source was identified. Two children
      were symptomatic. Possible dog-to-child transmission was established for one of
      the symptomatic cases. All contact-tracing results were negative. Other
      microscopically detected parasites (Blastocystis hominis, Endolimax nana cysts,
      Entamoeba coli cysts and Iodamoeba butschlii cysts) were found in 4% of children.
      In summary, a substantial level of Giardiasis may be prevalent in some of
      Berlin's kindergartens, despite standard hygienic measures being followed. The
      relatively high prevalence in one kindergarten indicates the need for further
      studies to identify risk factors for children, which may help to guide possible
      interventions and strategies. Giardiasis should be considered as a differential
      diagnosis in children with unclear gastrointestinal symptoms. Additional
      education and training on proper toilet and food hygiene may further reduce the
      possibility of child-to-child transmission.

PMID- 19404677
TI  - RfaB, a galactosyltransferase, contributes to the resistance to detergent and the
      virulence of Salmonella enterica serovar Enteritidis.
AB  - In this study, a deletion mutant of rfaB (DeltarfaB) was observed to be
      susceptible to sodium dodecyl sulfate and less tolerant to bile salts. In
      addition, pre-incubation in 10% bile salts increased bacterial tolerance to 30%
      bile salts. We also showed that the DeltarfaB mutant invaded HeLa cells less than
      the wild type and resulted in a lower ratio of intracellular bacteria.
      Competitive infection of mice showed that the DeltarfaB mutant was defective in
      the colonization of host organs and was cleared more quickly in fecal shedding.
      Transforming of a plasmid containing a wild-type allele of rfaB (pRB3-rfaB)
      partially rescued the defect of the DeltarfaB mutant. The results suggest that
      RfaB, which is responsible to add the glycosyl residue to the core
      lipopolysaccharide, contributes to the tolerance to detergent and the virulence
      of Salmonella enterica serovar Enteritidis.

PMID- 19404679
TI  - Regions associated with repression of the barley (Hordeum vulgare) VERNALIZATION1
      gene are not required for cold induction.
AB  - Activity of the VERNALIZATION1 (VRN1) gene is required for flowering in temperate
      cereals such as wheat and barley. In varieties that require prolonged exposure to
      cold to flower (vernalization), VRN1 is expressed at low levels and is induced by
      vernalization to trigger flowering. In other varieties, deletions or insertions
      in the first intron of the VRN1 gene are associated with increased VRN1
      expression in the absence of cold treatment, reducing or eliminating the
      requirement for vernalization. To characterize natural variation in VRN1, the
      first intron of the barley (Hordeum vulgare) VRN1 gene (HvVRN1) was assayed for
      deletions or insertions in a collection of 1,000 barleys from diverse
      geographical regions. Ten alleles of HvVRN1 containing deletions or insertions in
      the first intron were identified, including three alleles that have not been
      described previously. Different HvVRN1 alleles were associated with differing
      levels of HvVRN1 expression in non-vernalized plants and with different flowering
      behaviour. Using overlapping deletions, we delineated regions in the HvVRN1 first
      intron that are associated with low levels of HvVRN1 expression in non-vernalized
      plants. Deletion of these intronic regions does not prevent induction of HvVRN1
      by cold or the maintenance of increased HvVRN1 expression following cold
      treatment. We suggest that regions within the first intron of HvVRN1 are required
      to maintain low levels of HvVRN1 expression prior to winter but act independently
      of the regulatory mechanisms that mediate induction of HvVRN1 by cold during
      winter.

PMID- 19404680
TI  - Expression of four pha genes involved in poly-beta-hydroxybutyrate production and
      accumulation in Rhodobacter sphaeroides FJ1.
AB  - A cluster of genes encoding polyhydroxybutyrate (PHB) depolymerase (phaZ), PHB
      synthase (phaC), phasin (phaP), and the regulator protein (phaR) was previously
      identified in Rhodobacter sphaeroides FJ1 (R. sphaeroides FJ1). In this study, we
      investigated the role of the PhaR protein on the expression of the pha genes.
      Immunoblot analysis revealed that the expressions of phaP, phaZ and phaR genes in
      wild-type cells of R. sphaeroides FJ1 are repressed during the active growth
      phase, with the exception of phaC. A phaR deletion mutant of R. sphaeroides FJ1
      was constructed, and the basal level of phaP and phaZ expression in this mutant
      was markedly increased. Electrophoretic mobility shift assays demonstrated that
      PhaR binds to the promoter region of phaP as well as those of phaR and phaZ.
      These results suggest that the PhaR protein is a repressor of phaP, phaR, and
      phaZ genes in R. sphaeroides FJ1.

PMID- 19404681
TI  - Kinetic studies of the oxidation of glutathione in protein refolding buffer.
AB  - Here, we examined the change of glutathione (GSH) under different conditions and
      determined the appropriate kinetic schemes to describe its change of
      concentration. GSH was continuously oxidized into glutathione disulfide (GSSG) as
      incubation period increased at the temperatures ranging from 10 to 50 degrees
      Celsius while certain oxidation by-products were also observed at the later stage
      of reaction at higher temperatures (70-90 degrees Celsius). The addition of 0.3
      mM GSSG in 3 mM GSH solution delayed the onset of GSH oxidation without
      significantly changing the rate of GSH oxidation. Our results also revealed that
      GSH oxidation could be facilitated upon the addition of copper (II) ion whereas
      GSH oxidation was found to be decelerated when EDTA was present. In kinetic
      analysis, the reaction orders of GSH oxidation under various conditions were
      determined. Moreover, the temperature dependence of the rate of GSH oxidation was
      modeled by Arrhenius and Eyring equations and resultant activation parameters
      were also presented.

PMID- 19404682
TI  - Treatment of domestic wastewater in an up-flow anaerobic sludge blanket reactor
      followed by moving bed biofilm reactor.
AB  - The performance of a laboratory-scale sewage treatment system composed of an up
      flow anaerobic sludge blanket (UASB) reactor and a moving bed biofilm reactor
      (MBBR) at a temperature of (22-35 degrees C) was evaluated. The entire treatment
      system was operated at different hydraulic retention times (HRT's) of 13.3, 10
      and 5.0 h. An overall reduction of 80-86% for COD(total); 51-73% for
      COD(colloidal) and 20-55% for COD(soluble) was found at a total HRT of 5-10 h,
      respectively. By prolonging the HRT to 13.3 h, the removal efficiencies of
      COD(total), COD(colloidal) and COD(soluble) increased up to 92, 89 and 80%,
      respectively. However, the removal efficiency of COD(suspended) in the combined
      system remained unaffected when increasing the total HRT from 5 to 10 h and from
      10 to 13.3 h. This indicates that, the removal of COD(suspended) was independent
      on the imposed HRT. Ammonia-nitrogen removal in MBBR treating UASB reactor
      effluent was significantly influenced by organic loading rate (OLR). 62% of
      ammonia was eliminated at OLR of 4.6 g COD m(-2) day(-1). The removal efficiency
      was decreased by a value of 34 and 43% at a higher OLR's of 7.4 and 17.8 g COD m(
      2) day(-1), respectively. The mean overall residual counts of faecal coliform in
      the final effluent were 8.9 x 10(4) MPN per 100 ml at a HRT of 13.3 h, 4.9 x
      10(5) MPN per 100 ml at a HRT of 10 h and 9.4 x 10(5) MPN per 100 ml at a HRT of
      5.0 h, corresponding to overall log(10) reduction of 2.3, 1.4 and 0.7,
      respectively. The discharged sludge from UASB-MBBR exerts an excellent settling
      property. Moreover, the mean value of the net sludge yield was only 6% in UASB
      reactor and 7% in the MBBR of the total influent COD at a total HRT of 13.3 h.
      Accordingly, the use of the combined UASB-MBBR system for sewage treatment is
      recommended at a total HRT of 13.3 h.

PMID- 19404683
TI  - Tympanic temperature in confined beef cattle exposed to excessive heat load.
AB  - Angus crossbred yearling steers (n = 168) were used to evaluate effects on
      performance and tympanic temperature (TT) of feeding additional potassium and
      sodium to steers exposed to excessive heat load (maximum daily ambient
      temperature exceeded 32 degrees C for three consecutive days) during seasonal
      summer conditions. Steers were assigned one of four treatments: (1) control; (2)
      potassium supplemented (diet containing 2.10% KHCO3); (3) sodium supplemented
      (diet containing 1.10% NaCl); or (4) potassium and sodium supplemented (diet
      containing 2.10% KHCO3 and 1.10% NaCl). Overall, additional KHCO3 at the 2% level
      or NaCl at the 1% level did not improve performance or heat stress tolerance with
      these diet formulations. However, the addition of KHCO3 did enhance water intake.
      Independent of treatment effects, TT of cattle displaying high, moderate, or low
      levels of stress suggest that cattle that do not adequately cool down at night
      are prone to achieving greater body temperatures during a subsequent hot day.
      Cattle that are prone to get hot but can cool at night can keep average tympanic
      temperatures at or near those of cattle that tend to consistently maintain lower
      peak and mean body temperatures. In addition, during cooler and moderately hot
      periods, cattle change TT in a stair-step or incremental pattern, while under hot
      conditions, average TT of group-fed cattle moves in conjunction with ambient
      conditions, indicating that thermoregulatory mechanisms are at or near maximum
      physiological capacity.

PMID- 19404684
TI  - Marine phospholipids--a promising new dietary approach to tumor-associated weight
      loss.
AB  - GOALS OF WORK: Advanced tumor disease very often evokes excessive loss of body
      weight. Among others, fish oil or marine fatty acid ethyl esters were
      investigated for treatment of cancer cachexia with controversial results. In this
      study, a new formulation of marine fatty acids was investigated, the marine
      phospholipids, with more than 50% of phospholipid-bound fatty acids being
      eicosapentaenoic and docosahexaenoic acid. MATERIALS AND METHODS: Thirty-one
      tumor patients with various tumor entities suffering from weight loss were asked
      to take marine phospholipids (1.5 g/day) as softgel capsules for a period of 6
      weeks. Compliance, body weight, appetite, and quality of life as well as the
      fatty acid profile in plasma and blood cells were monitored; 17 patients could be
      analyzed. MAIN RESULTS: Marine phospholipids were very well accepted; low-dose
      supplementation resulted in a significant increase of eicosapentaenoic and
      docosahexaenoic acid in plasma phospholipids; therefore, significantly reducing
      the n-6 to n-3 fatty acid ratio. A stabilization of body weight was achieved
      (median weight change of +0.6% after 6 weeks), while appetite and quality of life
      improved. CONCLUSIONS: These promising first results encourage further
      investigation of marine phospholipids in cancer care.

PMID- 19404685
TI  - Role of the cyclooxygenase pathway in chemotherapy-induced oral mucositis: a
      pilot study.
AB  - GOALS: Oral mucositis can be a significant and dose-limiting complication of high
      dose cancer therapy. Mucositis is a particularly severe problem in patients
      receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem
      cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury
      and pain through upregulation of pro-inflammatory prostaglandins, including
      prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n =
      3) pilot study was to examine the role of the COX pathway in causing mucosal
      injury and pain in chemotherapy-induced oral mucositis. MATERIALS AND METHODS: We
      collected blood, saliva, and oral mucosal biopsy specimens from three autologous
      HSCT patients at the following time-points before and after administration of
      conditioning chemotherapy: Day -10, +10, +28, and +100, where day 0 is day of
      transplant. RNA extracted from full-thickness tissue samples was measured by RT
      PCR for the following: COX-1, COX-2, microsomal prostaglandin E synthase (mPGES),
      IL-1beta, and TNF-alpha. Blood and saliva samples were measured by ELISA for PGE2
      and PGI2, which are markers of COX activity. Severity of oral mucositis was
      determined using the Oral Mucositis Index. Severity of pain due to oral mucositis
      was measured using a Visual Analog Scale. Relationships between the different
      variables were examined using Spearman rank correlation coefficients. MAIN
      RESULTS: Mean mucositis and pain scores increased significantly after
      administration of chemotherapy and then gradually declined. The correlation
      between changes in mucositis and pain scores was strong and statistically
      significant. The following additional correlations were statistically
      significant: between tissue COX-1 and pain; between tissue mPGES and pain;
      between salivary PGE1 and pain; between salivary PGI2 and pain. Other
      relationships were not statistically significant. CONCLUSIONS: Our finding of
      significant associations of pain scores with tissue COX-1 and mPGES, as well as
      salivary prostaglandins, is suggestive of a role for the cyclooxygenase pathway
      in mucositis, possibly via upregulation of pro-inflammatory prostaglandins.
      However, our small sample size may have contributed to the lack of significant
      associations between COX-2 and other inflammatory mediators with mucosal injury
      and pain. Thus, additional studies with larger numbers of subjects are warranted
      to confirm the involvement of the cyclooxygenase pathway in chemotherapy-induced
      mucositis.

PMID- 19404686
TI  - Mycorrhizal synthesis of Tuber indicum with two indigenous hosts, Castanea
      mollissima and Pinus armandii.
AB  - Tuber indicum is one of the most renowned commercialized fungi in China.
      Mycorrhizal investigations, however, have been carried out mainly with exotic
      trees. Up to now there is no detailed description of morphology of the
      mycorrhizae formed with the indigenous hosts of T. indicum. Containerized
      seedlings of two indigenous hosts of the fungus in southwestern China, Pinus
      armandii and Castanea mollissima, were inoculated with aqueous spore suspension
      of T. indicum in two kinds of substrates. Mycorrhizae began to form 4 months
      after inoculation and were harvested at 9 months. The contributing fungus of the
      mycorrhizae was confirmed to be T. indicum by morphological and ITS-rDNA sequence
      analyses. The morphology of emanating hyphae and epidermoid-like mantle
      appearance was similar to the mycorrhizae obtained with some European trees. The
      high morphological variation and the similarity to that of Tuber melanosporum
      makes it difficult to distinguish the mycorrhizae of the two species by
      morphology alone. The synthesis of mycorrhizae of T. indicum with its indigenous
      hosts will be of great significance for planned cultivation of the Asian black
      truffles.

PMID- 19404687
TI  - Biomechanical evaluation of a new fixation device for the thoracic spine.
AB  - The technology used in surgery for spinal deformity has progressed rapidly in
      recent years. Commonly used fixation techniques may include monofilament wires,
      sublaminar wires and cables, and pedicle screws. Unfortunately, neurological
      complications can occur with all of these, compromising the patients' health and
      quality of life. Recently, an alternative fixation technique using a metal clamp
      and polyester belt was developed to replace hooks and sublaminar wiring in
      scoliosis surgery. The goal of this study was to compare the pull-out strength of
      this new construct with sublaminar wiring, laminar hooks and pedicle screws.
      Forty thoracic vertebrae from five fresh frozen human thoracic spines (T5-12)
      were divided into five groups (8 per group), such that BMD values, pedicle
      diameter, and vertebral levels were equally distributed. They were then potted in
      polymethylmethacrylate and anchored with metal screws and polyethylene bands. One
      of five fixation methods was applied to the right side of the vertebra in each
      group: Pedicle screw, sublaminar belt with clamp, figure-8 belt with clamp,
      sublaminar wire, or laminar hook. Pull-out strength was then assessed using a
      custom jig in a servohydraulic tester. The mean failure load of the pedicle screw
      group was significantly larger than that of the figure-8 clamp (P = 0.001),
      sublaminar belt (0.0172), and sublaminar wire groups (P = 0.04) with no
      significant difference in pull-out strength between the latter three constructs.
      The most common mode of failure was the fracture of the pedicle. BMD was
      significantly correlated with failure load only in the figure-8 clamp and pedicle
      screw constructs. Only the pedicle screw had a statistically significant higher
      failure load than the sublaminar clamp. The sublaminar method of applying the
      belt and clamp device was superior to the figure-8 method. The sublaminar belt
      and clamp construct compared favorably to the traditional methods of sublaminar
      wires and laminar hooks, and should be considered as an alternative fixation
      device in the thoracic spine.

PMID- 19404689
TI  - Craniovertebral junction lesions: our experience with the transoral surgical
      approach.
AB  - The aim of this study is to review our experience with the transoral surgical
      management of anterior craniovertebral junction (CVJ) lesions with particular
      attention to the decision making and to the indication for a consecutive
      stabilization. During 10 years (1998-2007), 52 consecutive patients presenting
      exclusively fixed anterior compression at the cervicomedullary junction underwent
      transoral surgery. Mean age was 55.85 years (range 17-75 years). Encountered
      lesions were: malformation (32 cases), rheumatoid arthritis (11 cases), tumor (5
      cases) or trauma (4 cases). A total of 79% of patients presented with
      chronic/recurrent headache (cranial and/or high-cervical pain), 73% with varying
      degrees of quadrip aresis, and 29% with lower cranial nerve deficits. All of the
      patients but two, with posterior stabilization performed elsewhere, underwent
      synchronous anterior decompression and posterior occipitocervical fixation.
      Adjuncts to the transoral approach (Le Fort I with or without splitting of the
      palate), tailored to the local anatomy and to the extension of the lesions, were
      performed in seven cases. Follow-up ranged between 4 and 96 months. Of 35
      patients with severe preoperative neurological deficits, 33 improved. The
      remaining 15 patients who presented with mild symptoms, healed throughout the
      follow-up. Perioperative mortality occurred in two cases and surgical morbidity
      in eight cases (dural laceration, cerebrospinal fluid leak with meningitis,
      malocclusion, oral wound dehiscence and occipital wound infection). Delayed
      instability occurred in one patient because of cranial settling of C2 vertebral
      body. A successful surgery achieving a stable decompression at the CVJ is an
      expertise demanding procedure. It requires accurate preoperative evaluation and,
      appropriate choice of decompression technique and stabilization instruments.
      Enlarged transoral approaches (despite higher morbidity) are a supportive means
      in cases of severe basilar invagination, cranial extension of the lesion or
      limited jaw mobility.

PMID- 19404688
TI  - Comparison of single-level L4-L5 versus L5-S1 lumbar disc replacement: results
      and prognostic factors.
AB  - The aim of our prospective non-randomized clinical study was to analyze operative
      data, short-term results, safety, efficacy, complications, and prognostic factors
      for single-level total lumbar disc replacement (TLDR), and to compare results
      between different levels (L4-L5 vs. L5-S1). Thirty-six patients with single-level
      L4-L5 or L5-S1 TLDR, with 1-year minimum follow-up (FU), had complete clinical
      [SF36, visual analog scale (VAS), Oswestry Disability Index (ODI)] and
      radiological data, and were included in our study. Mean FU was 38.67 +/- 17.34
      months. Replaced level was L4-L5 in 12 (33.3%) cases, and L5-S1 in 24 cases
      (66.7%). Mean age at diagnosis was 41.17 +/- 7.14 years. 24 (66.7%) were females
      and 12 (33.3%) were males. Statistical analyses were assessed using t tests or
      Mann-Whitney test for continuous variables and Chi-square test or Fisher's exact
      test analyses for categorical variables. Univariate linear regression and binary
      logistic regression analyses were utilized to evaluate the relationship between
      surgical outcomes and covariates (gender, age, etiology, treated level, pre
      operative SF36, ODI, and VAS). Mean operative time was 147.03 +/- 30.03 min. Mean
      hospital stay was 9.69 +/- 5.39 days, and mean return to ambulation was 4.31 +/-
      1.17 days. At 1-year FU, patients revealed a statistical significant improvement
      in VAS pain (P = 0.000), ODI lumbar function (P = 0.000), and SF36 general health
      status (P = 0.000). Single-level TLDR is a good alternative to fusion for chronic
      discogenic low back pain refractory to conservative measures. Our study confirmed
      satisfactory clinical results for monosegmental L4-L5 and L5-S1 disc prosthesis,
      with no difference between the two different levels for SF36 (P = 0.217), ODI (P
      = 0.527), and VAS (P = 0.269). However, replacement of the L4-L5 disc is affected
      by an increased risk of complication (P = 0.000). There were no prognostic
      factors for intraoperative blood loss or return to ambulation. Age (P = 0.034)
      was the only prognostic factor for operative time. Hospital stay was affected by
      level (P = 0.036) and pre-op VAS (P = 0.006), while complications were affected
      by the level (P = 0.000) and pre-op ODI (P = 0.049). Complete pre-operative
      assessment (in particular VAS and ODI questionnaires) is important because more
      debilitating patients will have more hospital stay and higher complications or
      complaints. Patients had to be informed that complications, possibly severe, are
      particularly frequent (80.6%).

PMID- 19404690
TI  - Cervical fixation in the pediatric patient: our experience.
AB  - The surgical management of cervical instability in children is a challenging
      issue. Although the indications for internal fixation are similar to those for
      adults, accurate pre-surgery study and sharp surgical techniques are necessary
      because of the size of such patients' anatomy, their peculiar tissue biology and
      the wide spectrum of diseases requiring cervical fusion. Our case study is made
      up of 31 patients, 15 male and 16 female, with an average age of 7 years and 6
      months (2 years and 6 months to 18 years) who underwent cervical fusion for
      instability. Their physical condition presented various different pathologies
      ranging from congenital deformity, systemic skeletal disease, tumors, trauma,
      post-surgery instability. We performed occipito-cervical fusion in 11 cases, 5 of
      which involved stabilization at the cranium-vertebral junction. We used
      instrumentation in 13 cases (3 sublaminar wiring, 10 rigid adult
      instrumentation). We used rigid adult instrumentation in three patients under 10
      years of age, treated by rod, occipital screws and sublaminar hook
      instrumentation in steel C0-C2 (9-year-old male, affected by os odontoideum in
      Down's syndrome; male of 7 years and 10 months, affected by os odontoideum in
      Down's syndrome; female of 4 years and 6 months with occipito-cervical stenosis
      and C0-C2 instability in Hurler's syndrome). We operated on two patients under 3
      years of age, using sublaminar wiring with bone precursors and allograft at level
      C0-C2 (one of these was a 30-month-old male with post-traumatic instability C0
      C2, while the other was a 17-month-old male with C0-C2 instability in Larsen's
      syndrome). The average follow-up age was 7 years and 1 month (between 1 and 18
      years). Cervical fusion was assessed by X-ray examinations at 4th and 12th weeks
      and at 6th and 12th months after surgery. Where implants could allow, RMN
      examination was performed at 1st month after surgery. In the other cases, in
      which implants do not allow RMN to be performed, CT scan and standard X-rays were
      carried out, and new X-rays were performed every other year. We experienced two
      cases of sublaminar wiring rupture without impairment of bone fusion. No patient
      suffered major complications (infection and osteomyelitis, rigid instrumentation
      mobilization, incomplete fusion with instability, neurologic impairment,
      insufficient cervical spine range of movement to cope with everyday life
      activities, cervical pain). Even though most authors still indicate that rigid
      instrumentation should be performed in cases over 10 years of age and sublaminar
      wiring in cases over 3 years of age, our findings demonstrate that this age limit
      can be lowered. We have treated children under 10 years of age by rigid adult
      instrumentation and under 36 months of age by wiring. The anatomic size of the
      patient is the most important factor in determining the use of instrument
      arthrodesis to treat pediatric cervical spine instability. Although not easy, it
      is possible and preferable in many cases to adapt fixation to child cervical
      spine even in very young patients.

PMID- 19404691
TI  - Implantation of amniotic membrane to reduce postlaminectomy epidural adhesions.
AB  - Postlaminectomy epidural adhesion is implicated as a main cause of "failed back
      surgery syndrome" and associated with increased risk of complications during
      revision surgery. Various materials acting as mechanical barriers to reduce
      fibroblasts infiltration into epidural space have met with limited success. In
      present research, amniotic membrane (AM) was studied to investigate its effects
      on reducing epidural scar adhesion after laminectomy in a canine model.
      Laminectomy sites were created at L-1, L-3, L-5, and L-7 levels in 24 adult
      mongrel dogs. Freeze dried AM (FAM), cross-linked AM (CAM), and autologous free
      fat (AFF) were implanted, respectively, at a randomly assigned site in each dog
      with the remaining untreated site serving as internal control. The animals were
      sacrificed at 1, 6, and 12 weeks postoperatively. Then, gross pathologic
      observation including scar amount and adhesion tenacity, qualitative histology
      evaluation, and quantitative histology analysis were compared. Gross observation
      demonstrated that scar amount and adhesion tenacity of CAM group were
      significantly lower in comparison with those of FAM and non-treatment groups. A
      white, slightly vascularized CAM layer covered the dura mater without tenacious
      scar adhesion. The histology analysis also indicated reduced fibroblasts
      infiltration and consequent epidural fibrosis, which were similar to the results
      of AFF group. In conclusion, the CAM is effective in reducing epidural fibrosis
      and scar adhesion after laminectomy in canine model. It is a promising
      biomaterial for future clinical applications.

PMID- 19404692
TI  - A novel sustained-release clotrimazole varnish for local treatment of oral
      candidiasis.
AB  - The use of dental varnish for therapeutic purposes has been reported for fluoride
      or antibacterial drugs. Our objectives were to develop a sustained-release
      varnish containing an antifungal drug (clotrimazole) for topical application and
      to evaluate the release rate of the drug in human saliva in comparison with an
      available commercial troche and their acceptance by healthy volunteers. Following
      in vitro optimization of the release rate from the varnish, we have embarked on a
      crossover comparative study assessing the oral sensations and pharmacokinetics of
      a 10-mg clotrimazole oral troche versus a 10-mg sustained-release clotrimazole
      varnish in 14 human volunteers over a period of 5 h. Saliva samples were assessed
      for clotrimazole concentration by high performance liquid chromatography
      analysis. The volunteers' evaluation of the varnish and troche (taste, other
      sensory changes, convenience, and oral suitability) were recorded. At all time
      points, salivary clotrimazole concentrations were higher, and the terminal half
      life was significantly prolonged in the varnish group in comparison to the
      control group. This can be attributed to continuous release of clotrimazole from
      the varnish formulation. The duration of the drug over the minimal inhibitory
      concentration, following application of the varnish, was more than threefold
      longer than following administration of the troche. The developed sustained
      release varnish can be applied in patients at a lower frequency than troches,
      thus, achieving higher patient compliance and efficacy. This novel varnish
      application can serve as the basis for a new treatment approach to oral
      candidiasis, a very common chronic opportunistic infection with improved clinical
      outcome.

PMID- 19404694
TI  - Effects of mouthrinses containing essential oils and alcohol-free chlorhexidine
      on human plaque acidogenicity.
AB  - The aim of this in vivo study was to evaluate the effect of two antimicrobial
      mouthrinses on dental plaque acidogenicity after a sucrose challenge. Twenty
      subjects, with a mean age of 59 years, participated in a double-blind
      intraindividual randomized study. Three mouthrinses were used in 16-day rinsing
      periods in addition to their regular mechanical oral hygiene: a solution with
      essential oils (EO), solution with alcohol-free chlorhexidine (CHX) and water
      (negative control). The three test periods were separated by 3-month washout
      periods. Changes in plaque acidogenicity were evaluated after a sucrose challenge
      at day 0 (baseline) and at day 17 of each mouthrinse period using the microtouch
      method. Both CHX and EO resulted at day 17 in statistically significant less
      attenuated pH falls compared to the water rinse. The CHX mouthrinse resulted in
      the least pronounced pH values compared with EO (ns) during the whole 30-min
      period. When calculated as area under the curve (AUC), significantly lower values
      (AUC(6.2) ) were found for CHX and EO at day 17 compared to day 0. A significant
      difference for AUC(6.2) between CHX and water was found at day 17. No
      statistically significant differences were found for any of the comparisons with
      AUC(5.7). The results from this study indicate that both the essential oils and
      the alcohol-free chlorhexidine reduced plaque acidogenicity after a sucrose
      challenge. Large interindividual variations were observed.

PMID- 19404695
TI  - Oral manifestations of HIV/AIDS in China: a review.
AB  - PURPOSE: The purpose of this study is to review the Chinese-language medical and
      dental literature from 1982 to 2008 on oral manifestations (OMs) of patients with
      HIV/AIDS for introducing the spectrum of OMs of the patients in China. MATERIALS
      AND METHODS: All data were extracted from 18 references which had used diagnostic
      criteria for HIV/AIDS. Four of the references had used the EC-Clearinghouse
      classification for oral lesions in HIV infection. The feasible overall rate and
      95% confidence interval (95%CI) of the data on OMs were calculated. RESULTS: Risk
      group analysis revealed that, of 203 patients, 64.3% were men and 35.7% were
      women (age range, 5 months to 64 years; mean age in three studies, 34.0, 34.3,
      and 36.1 years). Of these patients, 22.2% were infected by sexual contacts, 11.8%
      by intravenous drug use (IDU), 59.6% by blood or its products, 2.9% by mother to
      child transmission, and 3.4% were unclear. In 203 patients, oral candidiasis (OC)
      was the most common lesion (66%, 95%CI = 59.48-72.52%), followed by herpes
      simplex (HS) (22.2%, 95%CI = 16.48-27.92%), ulcerative stomatitis (14.8%, 95%CI =
      9.92-19.68%), salivary gland disease (11.3%, 95%CI = 6.94-15.66%), oral hairy
      leukoplakia (OHL) (9.8%, 95%CI = 5.71-13.89%), necrotizing gingivitis (5.9%,
      95%CI = 2.66-9.14%), Kaposi's sarcoma (2.9%, 95%CI = 0.59-5.21%), other malignant
      tumors (2.9%, 95%CI = 0.59-5.21%), and linear gingival erythema (2.0%, 95%CI =
      0.07-3.93%). CONCLUSIONS: The spectrum of OMs reported from China is similar to
      that described in the international literature. Present data are useful to
      supplement international resources of HIV/AIDS research.

PMID- 19404696
TI  - Ecotoxicological research and related legislation in Serbia.
AB  - INTRODUCTION: Several hot spots of severe freshwater pollution and sediment
      contamination (mostly heavy metals, polyaromatic hydrocarbons and polychlorinated
      biphenyls) have been identified in Serbia as the consequence of outdated
      environmental legislation, negligible amounts of properly treated waste waters
      and accidental spills. DISCUSSION: Since ecotoxicological methods have never been
      incorporated into risk assessment procedures, mandatory effluent discharge or
      ambient water monitoring programmes, ecotoxicological research, based on
      bioaccumulation studies, conventional ecotoxicological tests and, recently,
      biomarkers of exposure and effect have been restricted to independent small- to
      medium-scale studies, conducted, basically, to confirm, underline or oppose the
      results of chemical-based monitoring and to lament on inadequate environmental
      regulations/policy and management practice. Although hot and unresolved
      ecotoxicological problems still remain beyond the reach of ecotoxicological
      research currently conducted in Serbia, or are tackled only sporadically, it is
      to be expected that on-going research and institutional capacity building should,
      hopefully, increase the competence and competitiveness of scientific community
      and speed up the process of harmonisation of national environmental legislation
      and policy with European Union.

PMID- 19404697
TI  - Effect of body fat distribution on the transcription response to dietary fat
      interventions.
AB  - Combination of decreased energy expenditure and increased food intake results in
      fat accumulation either in the abdominal site (upper body obesity, UBO) or on the
      hips (lower body obesity, LBO). In this study, we used microarray gene expression
      profiling of adipose tissue biopsies to investigate the effect of body fat
      distribution on the physiological response to two dietary fat interventions.
      Mildly obese UBO and LBO male subjects (n = 12, waist-to-hip ratio range 0.93
      1.12) were subjected to consumption of diets containing predominantly either long
      chain fatty acids (PUFA) or medium-chain fatty acids (MCT). The results revealed
      (1) a large variation in transcription response to MCT and PUFA diets between UBO
      and LBO subjects, (2) higher sensitivity of UBO subjects to MCT/PUFA dietary
      intervention and (3) the upregulation of immune and apoptotic pathways and
      downregulation of metabolic pathways (oxidative, lipid, carbohydrate and amino
      acid metabolism) in UBO subjects when consuming MCT compared with PUFA diet. In
      conclusion, we report that despite the recommendation of MCT-based diet for
      improving obesity phenotype, this diet may have adverse effect on inflammatory
      and metabolic status of UBO subjects. The body fat distribution is, therefore, an
      important parameter to consider when providing personalized dietary
      recommendation.

PMID- 19404698
TI  - A depressing state of knowledge.

PMID- 19404699
TI  - Prevalence and clinical feature of the "overlap syndrome", obstructive sleep
      apnea (OSA) and chronic obstructive pulmonary disease (COPD), in OSA population.
AB  - PURPOSE: The association of chronic obstructive pulmonary disease (COPD) and
      obstructive sleep apnea (OSA), defined overlap syndrome by Flenley, is frequent.
      Aims of the present study were to assess the frequency of overlap syndrome in 168
      consecutive OSA patients, and to evaluate the functional pulmonary hemodynamic,
      and polysomnographic consequences of this association by comparing Overlap
      patients with OSA patients. METHODS: From the results of the pulmonary and
      polysomnographic investigation, patients were classified as OSA patients (group
      1), having an apneas/hypopneas index (AH/I) > 15/hr, and Overlap patients (group
      2), i. e. OSA patients with an obstructive spirographic pattern (FEV1<60%,
      FEV1/FVC<65%, RV>130%, RV/TLC>140% of predicted value) not reversible after beta2
      agonist inhalation. Group 1 consisted of 135 Patients (115 males, 20 females, age
      56+/-10 yr, BMI 32+/-6 Kg/m(2)); the group 2 included 33 patients (30 males, 3
      females, age 56+/-11 yr., BMI 34 +/- 6 Kg/m(2)). RESULTS: The OSA and Overlap
      patients were similar in most respects: age, BMI, clinical characteristic. In
      awake Overlap patients had lower PaO(2), higher PaCO(2) and Ppa (p<0.001), and an
      obstructive spirographic pattern, as compared to OSA patients. During sleep the
      overlap group had a higher AH/I and a lower mean SaO(2) (p<0.05), a reduction of
      the sleep efficency (p<0.05), and a reduction in the duration of 1NREM and REM
      sleep stage (p<0.05), as compared to group 1. CONCLUSION: In conclusion, an
      associated COPD is observed in more than 19% of OSA patients. Overlap patients
      are at increased risk of developing pulmonary hypertension and show a poorer
      quality of sleep as compared with OSA patients. The possibility of developing cor
      pulmonale should be given particular attention in the diagnosis and follow-up of
      Overlap patients.

PMID- 19404700
TI  - Depression in sleep disorders clinics.
AB  - PURPOSE: The purpose of this paper was to determine the incidence of depression
      in our sleep disorders clinics (and it's relation to patient characteristics) and
      to determine whether the incidence of depression varies in patients with and
      without sleep apnea. METHODS: The Beck Depression Inventory (BDI) was
      administered to evaluate patients for depression. We reviewed records of all new
      patients between November, 1995 and May, 1996 and determined their BDI scores and
      polysomnogram (PSC) results. Patients were divided based on their respiratory
      disturbance index (RDI); a cut off value of 15 was chosen. Patients were re
      divided based on the BDI score (13 or greater suggestive of depression). The age,
      sex, body mass index (BMI), BDI or RDI (as appropriate) and arousal indices were
      compared. RESULTS: Sixty-three patients were enrolled; 29% were depressed. BDI
      scores and PSG data were available in 42 patients. Those with a high RDI had
      significantly lower BDI scores and higher arousal indices. Those with a high and
      low BDI scores were not significantly different in any of the parameters
      evaluated. CONCLUSIONS: Symptoms of depression are commonly seen in a sleep
      clinic. In patients with symptoms suggestive of SA but with low RDI scores, a
      diagnosis of depression should be entertained. The presence of depression,
      however, should not negatively influence a decision to perform PSG.

PMID- 19404702
TI  - The risks of "Laissez-Faire".

PMID- 19404703
TI  - Heart block and nonocclusive mesenteric ischemia.

PMID- 19404701
TI  - Image techniques in the evaluation of the upper airway in the obstructive sleep
      apnea syndrome.

PMID- 19404704
TI  - Dynamics of parathyroid hormone secretion after total parathyroidectomy and
      autotransplantation.
AB  - BACKGROUND: Secondary hyperparathyroidism is a common complication in uremic
      patients. Total parathyroidectomy combined with partial autotransplantation into
      brachioradialis muscle has been the preference among the options for surgical
      treatment. This study was designed to evaluate the reserve and ability of
      suppression of autotransplanted parathyroid tissue using dynamics tests. METHODS:
      We studied, prospectively, 12 patients in recent (RP) and late (LP) postoperative
      of total parathyroidectomy with autotransplantation. For analysis of the
      secretory reserve capacity, we induced hypocalcemia by ethylenediaminetetraacetic
      acid (EDTA) infusion. Furthermore, for analysis of the ability for parathyroid
      hormone (PTH) suppression, the hypercalcemia test was used, by intravenous
      administration of calcium in LP. RESULTS: In RP, there was a decrease in the
      average serum levels of PTH, phosphorus, and alkaline phosphatase, which ranged
      from 13 to 231 (87 +/- 65) pg/ml, 2.3 to 6.2 (3.3 +/- 1.1) mg/dl, and 77 to 504
      (250 +/- 135) U/L, respectively, similar to that observed in LP. The analysis of
      the average curve of variations in PTH during testing of the stimulus with EDTA
      showed lack of secretion in RP and partial response in LP. Impaired suppression
      ability of the graft in LP was observed in the test with intravenous calcium.
      CONCLUSIONS: Total parathyroidectomy followed by partial autotransplantation was
      effective in reducing PTH serum levels in patients with terminal kidney disease.
      The elevation of serum calcium during the suppression test was not able to
      inhibit the autograft gland secretion of PTH. The assessment of parathyroid graft
      function demonstrated an inability to respond to the stimulus of hypocalcemia
      induced by EDTA, although there was a partial recovery, in late postoperative
      period.

PMID- 19404705
TI  - Gastroesophageal reflux disease and morbid obesity: is there a relation?
AB  - Gastroesophageal reflux disease (GERD) is highly prevalent in morbidly obese
      patients, and a high body mass index (BMI) is a risk factor for the development
      of GERD. However, the mechanism by which the BMI affects esophageal acid exposure
      is not completely understood. Although many advances have been made in the
      understanding of the pathophysiology of GERD, many aspects of the pathophysiology
      of this disease in morbidly obese patients remain unclear. The following review
      describes the current evidence linking esophageal reflux to obesity, covering the
      pathophysiology of the disease and the implications for treatment of GERD in the
      obese patient.

PMID- 19404707
TI  - Re: Surgical management of peritoneal dialysis peritonitis: the impact of
      peritoneal sclerosis.

PMID- 19404708
TI  - Intra-abdominal pressure and abdominal compartment syndrome in acute general
      surgery.
AB  - BACKGROUND: Intra-abdominal pressure (IAP) is a harbinger of intra-abdominal
      mischief, and its measurement is cheap, simple to perform, and reproducible.
      Intra-abdominal hypertension (IAH), especially grades 3 and 4 (IAP > 18 mmHg),
      occurs in over a third of patients and is associated with an increase in intra
      abdominal sepsis, bleeding, renal failure, and death. PATIENTS AND METHODS:
      Increased IAP reading may provide an objective bedside stimulus for surgeons to
      expedite diagnostic and therapeutic work-up of critically ill patients. One of
      the greatest challenges surgeons and intensivists face worldwide is lack of
      recognition of the known association between IAH, ACS, and intra-abdominal
      sepsis. This lack of awareness of IAH and its progression to ACS may delay timely
      intervention and contribute to excessive patient resuscitation. CONCLUSIONS: All
      patients entering the intensive care unit (ICU) after emergency general surgery
      or massive fluid resuscitation should have an IAP measurement performed every 6
      h. Each ICU should have guidelines relating to techniques of IAP measurement and
      an algorithm for management of IAH.

PMID- 19404706
TI  - Hyperparathyroidism and malnutrition with severe vitamin D deficiency.
AB  - BACKGROUND: Vitamin D deficiency and its associated problems are common in
      developing Asian countries and countries of the Middle East. Various factors,
      including poor nutritional status and other compounding factors such as dietary,
      cultural, ethnic, and environmental factors, play a major role in contributing to
      the poor calcium and vitamin D homeostasis. Vitamin D deficiency is thought to
      exacerbate signs and symptoms of hyperparathyroidism (HPT). In this overview, we
      present evidence of the impact of vitamin D and calcium deficiency on primary HPT
      (PHPT). METHODS: We performed an evidence-based review of articles published in
      the English language between January 1960 and June 2008. RESULTS: Level IV
      evidence suggests widespread calcium and vitamin D deficiency in developing
      countries (issue 1). Limited level IV evidence suggests malnutrition as a primary
      cause of calcium and vitamin D deficiency (issue 2). Level IV evidence suggests
      that calcium and vitamin deficiencies cause secondary HPT and possibly PHPT as
      well (issues 3 and 4). A literature search revealed only six studies that
      correlated vitamin D levels with clinical, biochemical, and pathologic features
      of PHPT (issue 5). These studies provide level IV evidence suggesting that
      vitamin D deficiency causes some specific clinical features of PHPT as well as
      exacerbating other features of the disease. CONCLUSIONS: In the developing
      countries, which have severe vitamin D and calcium deficient population, PHPT
      patients present with advanced disease and particularly severe bone symptoms.
      There is presently only level IV evidence of vitamin D status affecting the
      clinical severity of PHPT.

PMID- 19404710
TI  - Preoperative u-PAR gene expression in bone marrow indicates the potential power
      of recurrence in breast cancer cases.
AB  - INTRODUCTION: The clinical significance of isolated tumor cells (ITC) in
      peripheral blood (PB) and bone marrow (BM) as predictive markers in the
      recurrence or metastasis of breast cancer has not yet been determined. In the
      current study, we focused on the urokinase plasminogen activator receptor (u-PAR)
      gene as a powerful indicator of the potential to relapse after surgery. PATIENTS
      AND METHODS: We examined CK-7 and CK19 as an ITC marker and u-PAR as a candidate
      indicator for metastasis in PB and BM from 800 cases of breast cancer by
      quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR).
      Serum tumor markers, carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15
      3), were compared with u-PAR or CK status. RESULTS: CK7 in PB was positive in 262
      cases that showed a poorer disease-free survival (DFS) than 478 CK7(-) cases (P <
      0.05). The 153 cases of u-PAR(+) in BM showed significantly poorer DFS and
      overall survival (OS) than did the 579 cases of u-PAR(-) in BM (P < 0001 and P <
      0.0001, respectively). In PB, a significant difference was also observed between
      330 cases of u-PAR(+) and 437 cases of u-PAR(-) (P < 0.0001). The hazard ratio
      (HR) for prediction of recurrence was significantly higher in u-PAR (P < 0.0001;
      HR 0.0519) than the level of three serum tumor markers. DISCUSSION: u-PAR
      expresses in cancer cells during the dormant phase. The current findings revealed
      that the expression levels of u-PAR in PB and BM evaluated preoperatively
      indicate the potential to relapse or metastasize after surgery.

PMID- 19404709
TI  - Proanthocyanidin protects intestine and remote organs against mesenteric
      ischemia/reperfusion injury.
AB  - BACKGROUND: Intestinal ischemia/reperfusion (IR) induces a systemic inflammatory
      response and releases harmful substances that may affect the function and
      integrity of distant organs such as lung, liver, and kidney. We conducted this
      study to find out if proanthocyanidins (PA) has protective effects against
      mesenteric IR injury and mesenteric IR-induced intestinal and distant organ
      injury. MATERIALS AND METHODS: Thirty-two Sprague-Dawley rats were divided into
      four groups: control, control + PA, IR, IR + PA. The IR and IR + PA groups were
      subjected to mesenteric arterial ischemia for 60 min and reperfusion for 6 h. The
      Control + PA and IR + PA groups were administered PA (100 mg/kg/day via oral
      gavage) for 7 days prior to injury insult. We collected ileal and distant organ
      tissues, such as pulmonary, hepatic, and kidney specimens to measure tissue
      levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione
      peroxidase (GPx), and nitrite plus nitrate (NO(x)), and we then evaluated
      histological changes. RESULTS: In the IR group, significant increases in MDA and
      NO(x) levels and significant increases in SOD and GPx activities of intestine,
      liver, kidney, and lung were observed. The MDA and NO(x) levels were
      significantly lower, as were the SOD and GPx activities in the IR + PA group than
      that in the IR group. Although the intestine and distant organs damage scores
      were significantly higher in the IR group, these injuries were prevented by PA in
      the IR + PA group. CONCLUSIONS: This study demonstrates that PA has a significant
      effect in the protection of the intestine and the remote organs against
      mesenteric IR injury.

PMID- 19404713
TI  - [Iatrogenic dental and maxillary injuries associated with procedures performed by
      anesthesiologists].

PMID- 19404712
TI  - Role of technology assessment in orthopaedics.
AB  - A technology assessment is a literature-based research project that seeks to
      determine whether a medical device, drug, procedure, or biologic is effective or
      to summarize literature on a given technology. A well-conducted assessment is a
      form of secondary research that employs the same steps used in primary research
      studies (ie, well-designed clinical trials). The primary difference is that in
      technology assessment the investigator does not collect the raw data. Rather,
      (s)he must use data collected by someone else. Nevertheless, a well-designed
      assessment, like a well-designed study, employs the scientific method, which is a
      method designed to combat bias. When there is little available information, such
      as with new technologies, unbiased examinations can typically show that
      enthusiasm for that technology is not backed by much data. When there is more
      information, assessments can not only determine whether a technology is
      effective, but also how effective it is. Technology assessments can provide busy
      orthopaedic surgeons (who do not have the time to keep up with and critically
      evaluate current literature) with succinct information that enables them to
      rapidly determine what is and what is not known about any given medical
      technology.

PMID- 19404714
TI  - Abnormal aortic-to-radial arterial pressure gradients resulting in misdiagnosis
      of hemodynamic instability.

PMID- 19404715
TI  - Brain metastases in patients with pelvic or abdominal malignancy do not prevail
      in the posterior fossa: a retrospective study.
AB  - Pelvic and gastrointestinal tumors are generally considered to have a
      predilection to metastasize to the posterior fossa rather than to the
      supratentorial brain. Review of imaging of 100 patients with brain metastases
      from pelvic and gastrointestinal primary tumors and of 100 patients with brain
      metastases from other primary tumors did not reveal a difference in distribution
      of brain metastases between the two groups of patients. So, there is no evidence
      that pelvic and gastrointestinal tumors metastasize preferentially to the
      posterior fossa.

PMID- 19404711
TI  - Role of ischemic preconditioning in liver surgery and hepatic transplantation.
AB  - INTRODUCTION: The purpose of this review is to summarize intraoperative surgical
      strategies available to decrease ischemia-reperfusion injury associated with
      liver resection and liver transplantation. MATERIAL AND METHOD: We conducted a
      critical review of the literature evaluating the potential applications of
      hepatic ischemic preconditioning (IPC) for hepatic resection surgery and liver
      transplantation. In addition, we provide a basic bench-to-bedside summary of the
      liver physiology and cell signaling mechanisms that account for the protective
      effects seen with hepatic IPC.

PMID- 19404716
TI  - Parkinson's disease sleep scale, sleep logs, and actigraphy in the evaluation of
      sleep in parkinsonian patients.
AB  - The aim of this study was to compare the results of the day-to-day self
      evaluation of sleep quality by sleep logs with Parkinson's disease sleep scale
      (PDSS) in Parkinson's disease (PD) patients. Actigraphy was used as an
      independent analysis of nighttime activity interfering with sleep. A total of 71
      idiopathic PD patients and 21 age- and sex-matched normal individuals lacking any
      type of sleep disturbance were recruited. Sleep was evaluated by PDSS, 7-d sleep
      log and actigraphy. Sleep logs and PDSS showed reduced sleep quality and daytime
      somnolence scores in moderate/severe PD patients as compared to healthy controls.
      Significant correlations were found between sleep quality in sleep logs and all
      domains of PDSS sleep quality, except for the presence of nocturia, which
      correlated with nocturnal activity. PD severity and depression were the only
      predictors of reduced sleep quality. The retrospective and day-to-day sleep self
      evaluations were coincident. Reduced sleep quality was related to increased PD
      severity and depression scores.

PMID- 19404717
TI  - A small-scale randomized controlled trial of the revised new forest parenting
      programme for preschoolers with attention deficit hyperactivity disorder.
AB  - The revised new forest parenting programme (NFPP) is an 8-week psychological
      intervention designed to treat ADHD in preschool children by targeting, amongst
      other things, both underlying impairments in self-regulation and the quality of
      mother-child interactions. Forty-one children were randomized to either the
      revised NFPP or treatment as usual conditions. Outcomes were ADHD and ODD
      symptoms measured using questionnaires and direct observation, mothers' mental
      health and the quality of mother-child interactions. Effects of the revised NFPP
      on ADHD symptoms were large (effect size >1) and significant and effects
      persisted for 9 weeks post-intervention. Effects on ODD symptoms were less
      marked. There were no improvements in maternal mental health or parenting
      behavior during mother-child interaction although there was a drop in mothers'
      negative and an increase in their positive comments during a 5-min speech sample.
      The small-scale trial, although limited in power and generalizability, provides
      support for the efficacy of the revised NFPP. The findings need to be replicated
      in a larger more diverse sample.

PMID- 19404718
TI  - Prevalence of major depression in preschool children.
AB  - The prevalence of preschool major depressive disorder (MDD) was studied in the
      community. The whole population of children between 3 and 6 years attending
      preschool nurseries in three areas (one urban, one rural and one suburban) in
      Spain (n = 1,427) were contacted. Selection was by a two-stage procedure. At
      stage I, the ESDM 3-6, a screening measure for preschool depression, was used to
      identify a sample for more intensive interviewing. Sensitivity and specificity of
      the cut-off point of the ESDM 3-6 had been previously tested in a pilot study (n
      = 229). During the first stage, 222 preschool children (15.6%) were found to be
      probable depressives, because they scored 27 or more, the cut-off used. At stage
      II, the children were interviewed and diagnosed by the consensus of two
      clinicians, blind to the ESDM 3-6 results. DSM-IV diagnostic criteria were used
      to define caseness. A total of 16 children (1.12%) met the MDD criteria. The
      prevalence by areas was urban 0.87%, rural 0.88%, suburban 1.43%. Sex
      distribution prevalence was 1:1. This study is a contribution to the scarce
      epidemiology of preschool depression in the community.

PMID- 19404719
TI  - Interleukin 8 gene polymorphisms and susceptibility to restenosis after
      percutaneous coronary intervention.
AB  - Interleukin-8 is a strong mediator of inflammation and has been implicated in the
      biochemical pathways involved in a wide range of inflammatory diseases including
      atherosclerosis. We investigated the potential influence of two common functional
      polymorphisms of the interleukin (IL)-8 gene: -251A/T and 781C/T on
      susceptibility to in stent restenosis (ISR) following percutaneous coronary
      intervention (PCI). The hypothesis was tested by screening for the prevalence of
      the above polymorphisms in 201 coronary artery disease (CAD) patients subjected
      to PCI and presenting with symptoms or signs of recurrent ischemia. Patients were
      angiographically re-evaluated and formed the ISR group (n = 73) and the non-ISR
      group (n = 128) based on the presence or absence of ISR. One hundred and forty
      seven subjects without angiographic evidence of CAD formed a reference control
      group (non-CAD group). A borderline statistically significant higher frequency of
      the TT(251)TT(781) combined genotype was observed in patients with ISR on re
      evaluation compared with patients with normal follow-up angiography. The
      predominance of TT(251)TT(781) was independent of conventional risk factors for
      cardiovascular disease. Consequently, T(251)T(781) haplotype was significantly
      more common in the ISR group. The above observations indicate that the genetic
      diversity of the IL-8 gene influences patient susceptibility to ISR and suggests
      the implication of IL-8-mediated pathways in the process of ISR. However, the
      rarity of T(251)T(781) haplotype makes any clinical application of the above
      observations unfeasible.

PMID- 19404721
TI  - PCR-SSCP and sequence analysis of three Odontotermes spp. (order: isoptera;
      family: termitidae) on the basis of partial 16SrRNA gene.
AB  - Partial 16S gene fragments were amplified by using specific primers in few
      species/populations of termites of the genus Odontotermes
      (Isoptera:Termitidae:Macrotermitinae), and the PCR products were subjected to
      SSCP analysis. Three haplotypes obtained were subjected to sequencing. The
      sequences obtained were characterized to see the frequencies of each nucleotide
      bases. High A + T content was observed. The inter-specific pairwise sequence
      divergence in Odontotermes spp. ranged from 0% to 4.8% across the entire 16S gene
      fragment. Identical sequences were found between two populations of O. horni.
      Individuals of different species having Type-I conformational pattern, i.e. O.
      obesus (-AI) and O. horni (-MI), as well as Type-II of O. obesus (-UII) and O.
      bhagwatii (-CHII) had no percent diversity. Phylogenetic trees drawn on the basis
      of distance Neighbour-joining method revealed clustering of individuals according
      to their genera and families.

PMID- 19404720
TI  - Mechanism of attenuation by beta-hydroxy-beta-methylbutyrate of muscle protein
      degradation induced by lipopolysaccharide.
AB  - The mechanism of the effect of beta-hydroxy-beta-methylbutyrate (HMB) on protein
      degradation induced by lipopolysaccharide (LPS) has been evaluated in murine
      myotubes. HMB (50 muM) completely attenuated total protein degradation induced by
      LPS (1-100 ng/ml), formation of reactive oxygen species (ROS) and activation of
      caspase-3/-8. Specific inhibitors of caspase-3/-8 completely attenuated ROS
      production, total protein degradation and the LPS-induced autophosphorylation of
      dsRNA-dependent protein kinase (PKR). Protein degradation in response to LPS or
      ROS production was not seen in myotubes transfected with mutant PKRDelta6,
      suggesting that PKR was involved in ROS production, which was essential for total
      protein degradation. This was confirmed using the antioxidant butylated
      hydroxytoluene (BHT) which completely attenuated protein degradation in response
      to LPS. The link between PKR activation and ROS production was mediated through
      p38 mitogen-activated protein kinase (MAPK), which was activated by LPS in
      myotubes transfected with wild-type PKR, but not PKRDelta6. Both ROS production
      and protein degradation induced by LPS were completely attenuated by SB203580, a
      specific inhibitor of p38MAPK. This suggests that LPS induces protein degradation
      through a signalling cascade involving activation of caspase-3/-8, activation of
      PKR and production of ROS through p38MAPK, and that this process is attenuated by
      HMB.

PMID- 19404722
TI  - Electrolytic deposition of hydroxyapatite coating on thermal treated Ti-40Zr.
AB  - In this study, hydroxyapatite (HA) was coated on both thermal treated and
      untreated Ti-40Zr substrates by means of electrolytic deposition. It was
      predicted that the HA layer would increase the bioactivity and osteoconductivity
      of the Ti-40Zr substrate, and a thermal treatment would improve the bonding
      strength between the HA layer and Ti-40Zr substrate, and prevent the corrosion of
      the Ti-40Zr substrate. First, the Ti-40Zr samples were annealed at various
      temperatures (200, 300, 400, 500 and 600 degrees C respectively). After
      annealing, samples were immersed in a Ca(NO(3))(2).4H(2)O and
      (NH(4))(3)PO(4).3H(2)O solution for the electrolytic deposition of the HA
      coating. Various analyses of the coating were conducted, including surface
      morphology, phase structure, corrosion resistance, biocompatibility, and bond
      strength between HA and Ti-40Zr. Experimental results indicated that the bonding
      strength of the HA coating on the thermal treated Ti-40Zr was markedly improved
      when compared to that of the HA coating on an untreated Ti-40Zr alloy. The
      corrosion resistance of Ti-40Zr was also improved by the use of the thermal
      treatment, as shown by a potentiodynamic polarization test. Finally, osteoblast
      like cells cultured on the HA coating surface were found to have proliferated on
      all samples.

PMID- 19404723
TI  - Mechanical properties of organically modified silicates for bone regeneration.
AB  - In this paper, different organic-inorganic hybrid materials based in the CaO
      SiO(2)-poly(dimethyl siloxane) PDMS system have been characterised by means of
      nanoindentation and their static mechanical properties (Young's modulus, and
      hardness) have been investigated. These mechanical properties have been discussed
      in relation to the chemical composition and structure of the different hybrid
      materials. Besides, the mechanical behaviour of hybrid materials is visco-elastic
      and it therefore presents phenomena of creep that will be influenced by the
      temperature of the mechanical test; undoubtedly, a temperature of 37 degrees C
      accelerates the processes of creep.

PMID- 19404724
TI  - Telephone-administered cognitive behavioral therapy: a case study of anxiety and
      depression in Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic medical illness with a high incidence of
      psychiatric comorbidity, specifically depression and anxiety. Research on
      treatment of such psychiatric complications is scarce. Non-pharmaceutical
      treatment options are especially attractive. Cognitive behavioral therapy (CBT)
      is a psychotherapeutic treatment option that has been successful in other
      chronically medically ill populations with comorbid depression and anxiety. The
      current research had two aims. The first was to pilot the feasibility of
      screening and identifying PD patients with symptoms of anxiety and depression in
      a specialized outpatient clinic. The second aim was to pilot the feasibility of
      telephone-administered CBT for the treatment of depression and anxiety in persons
      with PD, which was done through a case series comparing telephone-administered
      CBT to a Support strategy. A fairly large portion (67.5%) of patients screened in
      the outpatient clinic were identified as having symptoms of anxiety and/or
      depression. Results also indicated that CBT delivered via the telephone is a
      useful approach for targeting psychiatric symptoms in this population. A case
      example is given to illustrate the clinical considerations associated with
      delivering therapy via telephone to persons with PD.

PMID- 19404725
TI  - Cognitive and behavioral treatments for anxiety and depression in a patient with
      an implantable cardioverter defibrillator (ICD): a case report and clinical
      discussion.
AB  - Implantable cardioverter-defibrillators (ICDs) are the treatment of choice for
      patients at risk for potentially life threatening arrhythmias. The associated
      stress of living with an implanted device and receiving ICD shock therapy has
      been noted to exert a psychological toll on the individual patient and family.
      Anxious and depressive symptomatology is frequently reported by these patients,
      thus creating a demand for tailored psychological interventions for this
      population. The current case report describes the components, delivery, and
      effectiveness of a targeted treatment approach for anxiety and depression in an
      individual with an ICD. Test results and interview data revealed significant
      improvements in multiple domains of cognitive, emotional, and behavioral
      functioning. Improvements in marital relations were also achieved. These
      treatment effects were maintained at follow-up and in the context of acute,
      medical stressors. Future clinical and research directions are also discussed.

PMID- 19404728
TI  - The principle of inverse effectiveness in multisensory integration: some
      statistical considerations.
AB  - The principle of inverse effectiveness (PoIE) in multisensory integration states
      that, as the responsiveness to individual sensory stimuli decreases, the strength
      of multisensory integration increases. I discuss three potential problems in the
      analysis of multisensory data with regard to the PoIE. First, due to 'regression
      towards the mean,' the PoIE may often be observed in datasets that are analysed
      post-hoc (i.e., when sorting the data by the unisensory responses). The solution
      is to design discrete levels of stimulus intensity a priori. Second, due to
      neurophysiological or methodological constraints on responsiveness, the PoIE may
      be, in part, a consequence of 'floor' and 'ceiling' effects. The solution is to
      avoid analysing or interpreting data that are too close to the limits of
      responsiveness, enabling both enhancement and suppression to be reliably
      observed. Third, the choice of units of measurement may affect whether the PoIE
      is observed in a given dataset. Both relative (%) and absolute (raw) measurements
      have advantages, but the interpretation of both is affected by systematic changes
      in response variability with changes in response mean, an issue that may be
      addressed by using measures of discriminability or effect-size such as Cohen's d.
      Most importantly, randomising or permuting a dataset to construct a null
      distribution of a test parameter may best indicate whether any observed inverse
      effectiveness specifically characterises multisensory integration. When these
      considerations are taken into account, the PoIE may disappear or even reverse in
      a given dataset. I conclude that caution should be exercised when interpreting
      data that appear to follow the PoIE.

PMID- 19404727
TI  - Implications of gain modulation in brainstem circuits: VOR control system.
AB  - Gain modulation is believed to be a common integration mechanism employed by
      neurons to combine information from various sources. Although gain fields have
      been shown to exist in some cortical and subcortical areas of the brain, their
      existence has not been explored in the brainstem. In the present modeling study,
      we develop a physiologically relevant simplified model for the angular vestibulo
      ocular reflex (VOR) to show that gain modulation could also be the underlying
      mechanism that modifies VOR function with sensorimotor context (i.e. concurrent
      eye positions and stimulus intensity). The resulting nonlinear model is further
      extended to generate both slow and quick phases of the VOR. Through simulation of
      the hybrid nonlinear model we show that disconjugate eye movements during the VOR
      are an inevitable consequence of the existence of such gain fields in the
      bilateral VOR pathway. Finally, we will explore the properties of the predicted
      disconjugate component. We will demonstrate that the apparent phase
      characteristics of the disconjugate response vary with the concurrent conjugate
      component.

PMID- 19404726
TI  - Mammary involution and breast cancer risk: transgenic models and clinical
      studies.
AB  - Postlactational involution is the process following weaning during which the
      mammary gland undergoes massive cell death and tissue remodeling as it returns to
      the pre-pregnant state. Lobular involution is the process by which the breast
      epithelial tissue is gradually lost with aging of the mammary gland. While
      postlactational involution and lobular involution are distinct processes, recent
      studies have indicated that both are related to breast cancer development.
      Experiments using a variety of rodent models, as well as observations in human
      populations, suggest that deregulation of postlactational involution may act to
      facilitate tumor formation. By contrast, new human studies show that completion
      of lobular involution protects against subsequent breast cancer incidence.

PMID- 19404729
TI  - "Touched" by light: event-related potentials (ERPs) to visuo-haptic stimuli in
      peri-personal space.
AB  - Parietal neuronal populations have been found which respond bimodally to visual
      and somatosensory input regarding one's own limbs or even perceived haptic input
      of a false limb (Graziano et al., Science 290:1782-1785, 2000). Further, neuronal
      populations have been observed which respond preferentially to visual stimuli
      presented in spatial congruence with our hands (Graziano, Proc Natl Acad Sci USA
      96:10418-10421, 1999). In this study, we examined event-related potentials (ERPs)
      elicited by laser dots projected onto or above participants' index and middle
      fingers during a sustained-attention task. We hypothesized that visual stimuli
      projected onto the hand would elicit differences in ERP deflections related to
      sensory gating and categorization in comparison to when projected close to the
      hand. Participants responded via a footswitch to rare target flashes of light
      occurring on or directly above the middle finger of the attended hand. We found
      enhanced amplitudes of the N1 and P3 deflections when the stimuli fell onto the
      finger tips as opposed to above them. Furthermore, the N1 for unattended stimuli
      was less suppressed when the lasers were projected onto the fingers.
      Behaviorally, participants were less accurate to targets when the lasers fell
      onto the fingers. We conclude that when the lasers appear to "touch" the
      participants, they act to automatically draw participants' attention. Thus visual
      stimuli projected onto the fingers of the 'unattended' hand are harder to filter
      out, leading to decreases in accuracy during task performance.

PMID- 19404730
TI  - Mismatch negativity with visual-only and audiovisual speech.
AB  - The functional organization of cortical speech processing is thought to be
      hierarchical, increasing in complexity and proceeding from primary sensory areas
      centrifugally. The current study used the mismatch negativity (MMN) obtained with
      electrophysiology (EEG) to investigate the early latency period of visual speech
      processing under both visual-only (VO) and audiovisual (AV) conditions. Current
      density reconstruction (CDR) methods were used to model the cortical MMN
      generator locations. MMNs were obtained with VO and AV speech stimuli at early
      latencies (approximately 82-87 ms peak in time waveforms relative to the acoustic
      onset) and in regions of the right lateral temporal and parietal cortices.
      Latencies were consistent with bottom-up processing of the visible stimuli. We
      suggest that a visual pathway extracts phonetic cues from visible speech, and
      that previously reported effects of AV speech in classical early auditory areas,
      given later reported latencies, could be attributable to modulatory feedback from
      visual phonetic processing.

PMID- 19404731
TI  - A biometric latent curve analysis of memory decline in older men of the NAS-NRC
      twin registry.
AB  - Previous research has shown cognitive abilities to have different biometric
      patterns of age-changes. We examined the variation in episodic memory (word
      recall task) for over 6,000 twin pairs who were initially aged 59-75, and were
      subsequently re-assessed up to three more times over 12 years. In cross-sectional
      analyses, variation in the number of words recalled independent of age was
      explained largely by non-shared influences (65-72%), with clear additive genetic
      influences (12-32%), and marginal shared family influences (1-18%). The
      longitudinal phenotypic analysis of the word recall task showed systematic linear
      declines over age, but several nonlinear models with more dramatic changes at
      later ages, improved the overall fit. A two-part spline model for the
      longitudinal twin data with an optimal turning point at age 74 led to: (a) a
      separation of non-shared environmental influences and transient measurement error
      (~50%); (b) strong additive genetic components of this latent curve (~44% at age
      60) with increases (over 50%) up to age 74, but with no additional genetic
      variation after age 74; (c) the smaller influences of shared family environment
      (~15% at age 74) were constant over all ages; (d) non-shared effects play an
      important role over most of the life-span but diminish after age 74.

PMID- 19404732
TI  - IL-17 stimulates migration of carotid artery vascular smooth muscle cells in an
      MMP-9 dependent manner via p38 MAPK and ERK1/2-dependent NF-kappaB and AP-1
      activation.
AB  - Inappropriate vascular remodeling is thought to be the main cause of restenosis
      following angioplasty. Migration of vascular smooth muscle cells (VSMC) into
      lumina, which is promoted by degradation of the extracellular matrix by matrix
      metalloproteinases (MMPs) plays a causal role in pathological vascular
      remodeling. The aim of the present research is to explore the effects of a novel
      cytokine, IL-17, on migration of VSMC and MMP-9 secretion. Carotid artery VSMC
      was isolated from Sprague-Dawley rats. Expression of MMP-9 and cell migration
      induced by IL-17 and its related signal pathway were detected. The results showed
      that IL-17-induced migration of VSMC in an MMP-9-dependent manner. IL-17-induced
      MMP-9 expression was via p38 MAPK and ERK1/2 dependent NF-kappaB and AP-1
      activation. The present results demonstrated that IL-17 may play a role in
      vascular remodeling and targeting IL-17 or its specific downstream mediators is a
      potentially novel therapeutic pathway for attenuating the post-angioplastic
      restenosis.

PMID- 19404733
TI  - A longitudinal study of childhood depression and anxiety in relation to weight
      gain.
AB  - Adult mood disturbances are highly correlated with obesity, although little is
      known about the developmental relationship between mood disorders and weight.
      This study investigated the relationship between childhood psychopathology and
      weight over the course of 3 years. Body Mass Index (BMI) percentiles and
      demographic data of children (ages 8-18) with depression (n = 143) or anxiety (n
      = 43) were compared to healthy controls (n = 99). Both childhood depression
      (chi(2) = 4.6, p = 0.03) and anxiety (chi(2) = 6.0, p = 0.01) were associated
      with increased BMI percentiles. Compared to controls, BMI percentiles of
      depressed females over the course of the study differed profoundly (chi(2) = 7.0,
      p = 0.01) and BMI percentiles of anxious females approached significance (chi(2)
      = 3.7, p = 0.06). Males with anxiety showed a greater trend towards overweight
      (chi(2) = 3.3, p = 0.07) in comparison to controls. The major finding that
      depression and anxiety are associated with increased BMI percentiles in a non
      obese sample suggests that childhood psychopathology is an important factor that
      should be carefully monitored.

PMID- 19404734
TI  - Association of genetic variation in mitotic kinases with breast cancer risk.
AB  - An RNAi-based functional screening of mitotic kinases in Drosophila recently
      identified a number of members of the kinome that are required for normal cell
      division. Depletion of these kinases resulted in a number of different mitotic
      abnormalities including spindle malformation, chromosome mis-segregation,
      centrosome amplification and failure of cytokinesis (Bettencourt-Dias et al. in
      Nature 432:980-987, 2004). Since mitotic defects are commonly observed in cancer
      cells, these kinases may contribute to tumor development and/or progression. To
      investigate whether common genetic variation in the mitotic kinases are
      associated with breast cancer risk, we genotyped 386 single nucleotide
      polymorphisms (SNPs) from 44 mitotic kinase genes, in 798 breast cancer cases and
      843 unaffected controls from a clinic-based study. A total of 22 SNPs from 13
      kinase genes displayed significant associations with breast cancer risk (P(trend)
      < or = 0.05), including two SNPs from FYN (rs6914091 and rs1465061) that remained
      of interest after accounting for multiple testing (q = 0.06). These associations
      were stronger when evaluating cases with estrogen and progesterone receptor
      positive tumors. In addition, haplotype-based tests identified significant
      associations with risk for common haplotypes of the MAST2 (P = 0.04) and MAP2K4
      (P = 0.006) genes. Although requiring replication, these findings suggest that
      genetic polymorphisms in mitotic kinases that have been implicated in chromosome
      instability and aneuploidy may contribute to the development of breast cancer.

PMID- 19404735
TI  - ATM germline mutations in women with familial breast cancer and a relative with
      haematological malignancy.
AB  - Biallelic inactivation of the ATM gene causes ataxia-telangiectasia (A-T), a
      complex neurological disease associated with a high risk of leukaemias and
      lymphomas. Mothers of A-T children, obligate ATM heterozygote mutation carriers,
      have a breast cancer (BC) relative risk of about 3. The frequency of ATM carriers
      in BC women with a BC family history has been estimated to be 2.70%. To further
      our clinical understanding of familial BC and examine whether haematological
      malignancies are predictive of ATM germline mutation, we estimated the frequency
      of heterozygote mutation carriers in a series of 122 BC women with a family
      history of both BC and haematological malignancy and without BRCA1/2 mutation.
      The gene screening was performed with a new high throughput method, EMMA
      (enhanced mismatch mutation analysis). Amongst 28 different ATM variants, eight
      mutations have been identified in eight patients: two mutations leading to a
      putative truncated protein and six being likely deleterious mutations. One of the
      truncating mutations was initially interpreted as a missense mutation,
      p.Asp2597Tyr, but is actually a splice mutation
      (c.7789G>T/p.Asp2597_Lys2643>LysfsX3). The estimated frequency of ATM
      heterozygote mutation carriers in our series is 6.56% (95% CI: 2.16-10.95), a
      significantly higher figure than that observed in the general population,
      estimated to be between 0.3 and 0.6%. Although a trend towards an increased
      frequency of ATM carriers was observed, it was not different from that observed
      in a population of familial BC women not selected for haematological malignancy
      as the frequency of ATM carriers was 2.70%, a value situated in the confidence
      interval of our study.

PMID- 19404736
TI  - The c.5242C>A BRCA1 missense variant induces exon skipping by increasing splicing
      repressors binding.
AB  - Several unclassified variants (UV) of BRCA1 can be deleterious by affecting
      normal pre-mRNA splicing. Here, we investigated the consequences at the mRNA
      level of the frequently encountered c.5242C>A UV in BRCA1 exon 18. We show that
      the c.5242C>A variant induces skipping of exon 18 in UV carriers and in vitro.
      This alteration predicted to disrupt the first BRCT domain of BRCA1. We show that
      two splicing repressors, hnRNP A1 and hnRNP H/F, display a significant preference
      toward binding with the mutated exon 18 and assemble into a protein complex.
      Sequence analysis of the region surrounding the c.5242C>A change reveals the
      presence of hnRNP A1 and hnRNP H/F binding sites, which are modified by several
      UVs. Mutation of these sites alters the RNA binding ability of both splicing
      regulators. In conclusion, our work supports the model of the pathogenicity of
      the c.5242C>A BRCA1 variant that induces exon skipping by creating a sequence
      with silencer properties. We propose that other UVs in exon 18 interfere with
      splicing complex assembly by perturbing the binding of hnRNP A1 and hnRNP H/F to
      their respective cis-elements. RNA analysis is therefore necessary for the
      assessment of the consequences of UVs on splicing of disease-associated genes and
      to enable adequate genetic counseling for breast/ovarian cancer families.

PMID- 19404737
TI  - Extracellular matrix fibrotic markers in heart failure.
AB  - Given the importance of fibrous tissue in leading to myocardial dysfunction, non
      invasive assessment of fibrosis could prove a clinically useful tool in heart
      failure (HF) patients. Biomarkers may be used for early detection of otherwise
      subclinical disease, diagnostic assessment of an acute or chronic clinical
      syndrome, risk stratification of patients with a suspected or confirmed
      diagnosis, selection of an appropriate therapeutic intervention and monitoring
      the response to therapy. Extracellular matrix (ECM) biomarkers in HF are
      promising biomarkers. They are able to detect early changes in heart and large
      vessel structure and function and transition to HF. High ECM biomarker levels
      have been associated with poor outcome. The ability of treatment to reduce
      myocardial fibrosis in HF patients may be monitored by the measurement of various
      serum peptides arising from the metabolism of collagen types. Biomarkers may be
      selectively influenced by pharmacological agents.

PMID- 19404738
TI  - Transcriptional responses to environmental metal exposure in wild yellow perch
      (Perca flavescens) collected in lakes with differing environmental metal
      concentrations (Cd, Cu, Ni).
AB  - To investigate the mechanisms involved in metal stress in wild fish, yellow perch
      (Perca flavescens) were collected in eight lakes of the Rouyn-Noranda and Sudbury
      regions (Canada). Due to mining and smelting activities, these two regions indeed
      present a broad contamination gradient in metal concentrations (Cd, Cu, Zn and
      Ni; water, sediment and prey) and offer a unique research opportunity to
      investigate relationships between metal bioaccumulation and resulting deleterious
      effects in indigenous biota chronically exposed to metal mixtures. The expression
      level of genes encoding for proteins involved in metal detoxification
      (metallothioneins, mts), protein protection (heat shock protein-70, hsp-70),
      growth (insulin-like growth factor-1, igf-1), aerobic energy metabolism
      (cytochrome c oxydase, cco-1) and protection against oxidative stress (Cu/Zn
      superoxide dismutase, sod-1) were assessed in fish liver and muscle in
      association with protein and enzymatic assays for cytochrome c oxidase (CCO).
      Bioaccumulation of both Cd and Cu increased in response to higher ambient metal
      concentrations, but the two metals clearly have different modes of action. For
      Cd, changes in gene expression levels were more marked in the liver than in the
      dorsal muscle, whereas for Cu the opposite trend was observed. Hepatic Cd
      accumulation was linked to decreased cco-1 and sod-1 gene expression, whereas Cu
      accumulation was associated with a decrease in CCO enzymatic activity and an
      increase in total protein concentration and in cco-1, mts and hsp-70 gene
      expression levels. For Ni, no significant correlations were observed at the
      transcriptional level, but increasing hepatic Ni concentrations were
      significantly and positively correlated with protein concentrations and CCO
      activity. By coupling gene expression to biochemical and physiological endpoints,
      this work provides new insights into the mechanisms involved in metal stress and
      the adaptive response of fish chronically exposed to metal mixtures.

PMID- 19404739
TI  - Use of Cathorops spixii as bioindicator of pollution of trace metals in the
      Santos Bay, Brazil.
AB  - In the present study Cathorops spixii, was evaluated as a bioindicator fish for
      trace metal pollution. Concentrations of cobalt (Co), iron (Fe), selenium (Se)
      and zinc (Zn) were determined by Instrumental Neutron Activation Analysis in
      liver. Mercury (Hg) and methyl-mercury (MeHg) were analyzed by Cold Vapor Atomic
      Absorption Spectrometry in muscles and livers. High concentrations of Co, Fe, Se
      and Zn were observed in C. spixii from Santos Bay in comparison to fish collected
      in a non-polluted site in the same Brazilian coast. These trace metal
      concentrations were out of the permissible levels for human consumption.
      Although, Hg and MeHg levels were low, the C. spixii could still be used as an
      effective bioindicator to observe trace metal behaviors in the environment in
      function of the bioaccumulation process observed mainly by other analyzed trace
      metals. Thus, the use of this species is strongly recommended to monitor the
      effects and behavior of trace metal pollution in aquatic ecosystems in Brazil due
      to its bioaccumulation function.

PMID- 19404741
TI  - Metabolic effects of blocking lactate transport in brain cortical tissue slices
      using an inhibitor specific to MCT1 and MCT2.
AB  - A novel inhibitor of lactate transport, AR-C122982, was used to study the effect
      of inhibiting the monocarboxylate transporters MCT1 and MCT2 on cortical brain
      slice metabolism. We studied metabolism of L-[3-13C]lactate, and D-[1-13C]glucose
      under a range of conditions. Experiments using L-[3-13C]lactate showed that the
      inhibitor AR-C122982 altered exchange of lactate. Under depolarizing conditions,
      net flux of label from D-[1-13C]glucose was barely altered by 10 or 100 nM AR
      C122982. In the presence of AMPA or glutamate there were increases in net flux of
      label and metabolic pool sizes. These data suggest lactate may supply
      compartments in the brain not usually directly accessed by glucose. In general,
      it would appear that movement of lactate between cell types is not essential for
      metabolic activity, with the heavy metabolic workloads imposed being unaffected
      by inhibition of MCT1 and MCT2. Further experiments investigating the mechanism
      of operation of AR-C122982 are necessary to corroborate this finding.

PMID- 19404740
TI  - New insights into mechanisms of gamma-diketone-induced axonopathy.
AB  - We analyzed the impact of axonopathy-inducing agents 1,2-diacetylbenzene (1,2
      DAB) and 2,5-hexanedione (2,5-HD) on membrane-bound protein disulfide isomerase
      (mPDI) versus soluble PDI (sPDI), or PDI-family member thioredoxin (THX), and
      asked whether changes in PDI/THX were associated with production of
      oxidative/nitrosative species in the Sprague-Dawley rat. We show that 1,2-DAB and
      2,5-HD lower the abundance of sPDI and THX. However, the protein expression of
      mPDI is increased in 1,2-DAB axonopathy and neuroproteins became more S
      nitrosylated. The abundance of heme oxygenase-1 (HO-1) and isoforms of nitric
      oxide synthase (neuronal, endothelial, and inducible NOS) remained unchanged
      suggesting that S-nitrosylation occured via increased mPDI-transnitrosylation
      and/or diminished THX-denitrosylation. The transcription of PDI and glucose
      regulated protein-78 (GRP-78) remained unchanged indicating that post
      translational modifications, e.g. S-nitrosylation, mediate the pathogenesis of
      gamma-diketone axonopathy. These findings open opportunities for new therapeutic
      testing (e.g., supplementation with denitrosylating THX) in gamma-diketone
      induced axonal disease.

PMID- 19404743
TI  - Improvement of chloroperoxidase stability by covalent immobilization on chitosan
      membranes.
AB  - Chloroperoxidase (CPO) from Caldariomyces fumago was optimally covalently
      immobilized on chitosan membranes pretreated with 0.8 M glutaraldehyde at pH 3.5
      to give 3.18 mg CPO g(-1) support. Using monochlorodimedone (MCD) as assay
      substrate, the immobilized-CPO retained 40% activity at 50 degrees C after 40 min
      whereas free CPO retained only 0.02%. The residual activity for immobilized-CPO
      was 99 and 58% compared with 68 and 43% for free CPO in the presence of 1.5 M
      urea and 300 microM H(2)O(2), respectively, after 20 h.

PMID- 19404744
TI  - Molecular analysis of antioxidant genes in the extremohalophile marine bacterium
      Exiguobacterium sp. CNU020.
AB  - Exiguobacterium sp. CNU020, an alkaliphile and extremohalophile bacterium, is
      resistant to 20 mM H(2)O(2), a concentration that is lethal to most bacteria.
      Representative antioxidant genes of catalase and superoxide dismutase (SOD),
      obtained by PCR amplification of the genomic DNA, were characterized: the 252-bp
      catalase gene shared 77% similarity in the deduced amino acid sequence to that of
      E. oxidotolerans T-2-2(T). The 420-bp SOD gene had the closest similarity (94.3%)
      to the manganese-SOD of E. sibiricum 255-15. Through activity-staining analysis,
      stain CNU020 had at least four catalase isoforms: C1, C2, C3 and C4. Expression
      of each catalase isoform was dependent on the growth phase and oxidants but two
      catalases (C3 and C4) were always induced and expressed at a similar rate,
      indicating that they were constitutively expressed. RT-PCR-based expression
      analysis at the transcriptional level suggested that the catalase gene is
      strongly expressed in response to 2 mM H(2)O(2), 0.2 mM Paraquat and 0.2 mM
      menadione. However, the SOD gene exhibited no observable expression pattern with
      2 mM H(2)O(2) despite its strong expression when exposed to Paraquat and
      menadione.

PMID- 19404745
TI  - In vivo conjugation-coupled recombinational cloning of a Streptomyces lividans
      chromosomal telomeric DNA using a linear plasmid.
AB  - The high efficiency of homologous recombination in yeast and bacteria makes it
      useful for recombinational cloning of large genomic segments in vivo. The low
      efficiency of homologous recombination in Streptomyces has hindered the
      development of this cloning method. Unlike the inefficient mobilization of
      chromosomal markers, conjugative plasmid transfer is very efficient in
      Streptomyces. Here we report that the conjugation-coupled recombination procedure
      can be used to transfer a 10 kb chromosomal telomeric segment of Streptomyces
      lividans into a linear plasmid. The plasmid predominated in the population of
      cells after transfer into recipients. These results may promote the development
      of the recombinational cloning of large chromosomal segments in Streptomyces in
      vivo.

PMID- 19404746
TI  - Incorporation of non-natural modules into proteins: structural features beyond
      the genetic code.
AB  - The biotechnological application of enzymes necessitates a permanent quest for
      new biocatalysts. Among others, improvement of catalytic activity, modification
      of substrate specificity, or increase in stability of the enzymes are desirable
      goals. The exploration of homologous enzymes from various sources or DNA-based
      methods, like site-directed mutagenesis or directed evolution, yield an
      incredible variety of biocatalysts but they all rely on the restricted number of
      canonical amino acids. Chemistry offers an almost unlimited palette of additional
      modifications which can endow the proteins with improved or even completely new
      properties. Numerous techniques to furnish proteins with non-natural amino acids
      or non-proteinogenic modules have been introduced and are reviewed with special
      focus on expressed protein ligation, a method that combines the potential of
      protein biosynthesis and chemical synthesis.

PMID- 19404747
TI  - Crystal structures, DNA-binding studies and antioxidant  activities of the
      Ln(III) complexes with 7-methoxychromone-  3-carbaldehyde-isonicotinoyl
      hydrazone.
AB  - The neutral mononuclear Ln(III) complexes (Ln = La, Sm) with 7-methoxychrom-one-3
      carbaldehyde-isonicotinoyl hydrazone ligand (L) have been synthesized,
      characterized and investigated their interactions with calf-thymus DNA. The
      results show that the binding affinity of the La(III) complex is stronger than
      that of the Sm(III) complex and that of the ligand (L). Furthermore, the
      antioxidant activities of the ligand (L) and its Ln(III) complexes (Ln = La, Sm)
      were studied in detail.

PMID- 19404748
TI  - Transcriptional responses of Haemophilus parasuis  to iron-restriction stress in
      vitro.
AB  - Haemophilus parasuis is the causative agent of Glasser's disease, which is
      responsible for the increasing economic losses in the pig industry worldwide. In
      this study, selective capture of transcribed sequences approach was used to
      investigate the transcriptional responses of H. parasuis to iron-restriction
      stress. Thirty-six genes were identified to be up-regulated under iron-restricted
      conditions. Knowledge of the genes involved in adaptation to environments
      encountered during disease will help understand the mechanisms of pathogenesis
      for this economically significant bacterium.

PMID- 19404749
TI  - Anti-diabetic effects of vanadium(III, IV, V)-chlorodipicolinate complexes in
      streptozotocin-induced diabetic rats.
AB  - Vanadium(III, IV, V)-chlorodipicolinate (dipic-Cl) complexes, including
      H[VIII(dipic-Cl)2] . 5H2O (V3dipic-Cl), VIVO(dipic-Cl)(H2O)2 (V4dipic-Cl) and
      K[VVO2(dipic-Cl)] (V5dipic-Cl), were prepared with the indicated oxidation
      states. Our aim was to evaluate the anti-diabetic effects of V3dipic-Cl, V4dipic
      Cl and V5dipic-Cl in streptozotocin-induced diabetic rats. Vanadium complexes
      were orally administered to diabetic rats at concentrations of 0.1-0.3 mg/ml in
      the drinking water. We found that vanadium-chlorodipicolinate (V-dipic-Cl)
      complexes at the concentration of 0.1 mg/ml did not exhibit blood glucose
      lowering effects when administered to diabetic rats for 20 days. However, the
      levels of fasting blood glucose in diabetic rats were decreased after treatment
      with 0.3 mg/ml of V4dipic-Cl and V5dipic-Cl complexes for the following 20 days.
      Although administration of both V4dipic-Cl and V5dipic-Cl significantly lowered
      diabetic hyperglycemia, the vanadium intake from administration of V4dipic-Cl is
      nearly 1.5-fold greater compared to that of V5dipic-Cl. Treatment with the
      H2dipic-Cl ligand and all three V-dipic-Cl complexes significantly lowered serum
      cholesterol, while administration of the V5dipic-Cl complex lowered serum
      cholesterol significantly more than administration of the ligand alone. Treatment
      with ligand alone did not have an effect on serum triglyceride, while
      administration of the V4dipic-Cl and V5dipic-Cl significantly lowered the
      elevated serum triglyceride associated with diabetes. Oral administration of the
      ligand and all V-dipic-Cl complexes did significantly lower diabetes elevated
      serum alkaline phosphatase. Treatment with H2dipic-Cl ligand and V4dipic-Cl and
      V5dipicCl significantly lowered diabetes elevated aspartate amino transferase.
      These results indicate that the health of the treated animals did not seem to be
      further compromised compared to that of diabetic animals. In addition, oral
      administration of H2dipic-Cl, V3dipic-Cl, V4dipic-Cl and V5dipic-Cl did not alter
      diabetic serum creatinine and blood urea nitrogen levels, suggesting no
      significant side effects of vanadium treatment on renal functions at the dose of
      0.3 mg/ml in diabetic rats. The results presented here suggest that the anti
      diabetic effects of treatment with V-dipic-Cl complexes were likely associated in
      part with the oxidation state of vanadium.

PMID- 19404751
TI  - Exogenous ABA accentuates the differences in root hydraulic properties between
      mycorrhizal and non mycorrhizal maize plants through regulation of PIP
      aquaporins.
AB  - The arbuscular mycorrhizal (AM) symbiosis has been shown to modulate the same
      physiological processes as the phytohormone abscisic acid (ABA) and to improve
      plant tolerance to water deficit. The aim of the present research was to evaluate
      the combined influence of AM symbiosis and exogenous ABA application on plant
      root hydraulic properties and on plasma-membrane intrinsic proteins (PIP)
      aquaporin gene expression and protein accumulation after both a drought and a
      recovery period. Results obtained showed that the application of exogenous ABA
      enhanced osmotic root hydraulic conductivity (L) in all plants, regardless of
      water conditions, and that AM plants showed lower L values than nonAM plants, a
      difference that was especially accentuated when plants were supplied with
      exogenous ABA. This effect was clearly correlated with the accumulation pattern
      of the different PIPs analyzed, since most showed reduced expression and protein
      levels in AM plants fed with ABA as compared to their nonAM counterparts. The
      possible involvement of plant PIP aquaporins in the differential regulation of L
      by ABA in AM and nonAM plants is further discussed.

PMID- 19404750
TI  - The tomato brassinosteroid receptor BRI1 increases binding of systemin to tobacco
      plasma membranes, but is not involved in systemin signaling.
AB  - The tomato wound signal systemin is perceived by a specific high-affinity,
      saturable, and reversible cell surface receptor. This receptor was identified as
      the receptor-like kinase SR160, which turned out to be identical to the
      brassinosteroid receptor BRI1. Recently, it has been shown that the tomato bri1
      null mutant cu3 is as sensitive to systemin as wild type plants. Here we explored
      these contradictory findings by studying the responses of tobacco plants
      (Nicotiana tabacum) to systemin. A fluorescently-labeled systemin analog bound
      specifically to plasma membranes of tobacco suspension-cultured cells that
      expressed the tomato BRI1-FLAG transgene, but not to wild type tobacco cells. On
      the other hand, signaling responses to systemin, such as activation of mitogen
      activated protein kinases and medium alkalinization, were neither increased in
      BRI1-FLAG-overexpressing tobacco cells nor decreased in BRI1-silenced cells as
      compared to levels in untransformed control cells. Furthermore, in transgenic
      tobacco plants BRI1-FLAG became phosphorylated on threonine residues in response
      to brassinolide application, but not in response to systemin. When BRI1
      transcript levels were reduced by virus-induced gene silencing in tomato plants,
      the silenced plants displayed a phenotype characteristic of bri1 mutants.
      However, their response to overexpression of the Prosystemin transgene was the
      same as in control plants. Taken together, our data suggest that BRI1 can
      function as a systemin binding protein, but that binding of the ligand does not
      transduce the signal into the cell. This unusual behavior and the nature of the
      elusive systemin receptor will be discussed.

PMID- 19404752
TI  - The Pakistan Risk of Myocardial Infarction Study: a resource for the study of
      genetic, lifestyle and other determinants of myocardial infarction in South Asia.
AB  - The burden of coronary heart disease (CHD) is increasing at a greater rate in
      South Asia than in any other region globally, but there is little direct evidence
      about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS)
      is an epidemiological resource to enable reliable study of genetic, lifestyle and
      other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over
      5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over
      5,000 matched controls aged 30-80 years. For each participant, information has
      been recorded on demographic factors, lifestyle, medical and family history,
      anthropometry, and a 12-lead electrocardiogram. A range of biological samples has
      been collected and stored, including DNA, plasma, serum and whole blood. During
      its next stage, the study aims to expand recruitment to achieve a total of about
      20,000 cases and about 20,000 controls, and, in subsets of participants, to
      enrich the resource by collection of monocytes, establishment of lymphoblastoid
      cell lines, and by resurveying participants. Measurements in progress include
      profiling of candidate biochemical factors, assay of 45,000 variants in 2,100
      candidate genes, and a genomewide association scan of over 650,000 genetic
      markers. We have established a large epidemiological resource for CHD in South
      Asia. In parallel with its further expansion and enrichment, the PROMIS resource
      will be systematically harvested to help identify and evaluate genetic and other
      determinants of MI in South Asia. Findings from this study should advance
      scientific understanding and inform regionally appropriate disease prevention and
      control strategies.

PMID- 19404753
TI  - Altered fast- and slow-twitch muscle fibre characteristics in female mice with a
      (S248F) knock-in mutation of the brain neuronal nicotinic acetylcholine receptor.
AB  - We generated a mouse line with a missense mutation (S248F) in the gene (CHRNA4)
      encoding the alpha4 subunit of neuronal nicotinic acetylcholine receptor (nAChR).
      Mutant mice demonstrate brief nicotine induced dystonia that resembles the
      clinical events seen in patients with the same mutation. Drug-induced dystonia is
      more pronounced in female mice, thus our aim was to determine if the S248F
      mutation changed the properties of fast- and slow-twitch muscle fibres from
      female mutant mice. Reverse transcriptase-PCR confirmed CHRNA4 gene expression in
      the brain but not skeletal muscles in normal and mutant mice. Ca(2+) and Sr(2+)
      force activation curves were obtained using skinned muscle fibres prepared from
      slow-twitch (soleus) and fast-twitch (EDL) muscles. Two significant results were
      found: (1) the (pCa(50) - pSr(50)) value from EDL fibres was smaller in mutant
      mice than in wild type (1.01 vs. 1.30), (2) the percentage force produced at pSr
      5.5 was larger in mutants than in wild type (5.76 vs. 0.24%). Both results
      indicate a shift to slow-twitch characteristics in the mutant. This conclusion is
      supported by the identification of the myosin heavy chain (MHC) isoforms. Mutant
      EDL fibres expressed MHC I (usually only found in slow-twitch fibres) as well as
      MHC IIa. Despite the lack of spontaneous dystonic events, our findings suggest
      that mutant mice may be having subclinical events or the mutation results in a
      chronic alteration to muscle neural input.

PMID- 19404754
TI  - Changes of the bacterial assemblages throughout an urban drinking water
      distribution system.
AB  - We analyzed the bacterial 16S rRNA gene diversity throughout the major components
      of the drinking water distribution system of a ca. 52,000-inhabitants city
      (Trikala City, Greece) in order to describe the changes of the bacterial
      assemblages and to detect possible bacterial pathogens which are not included in
      the standard monitoring process. Bacterial DAPI counts and DNA extraction was
      performed in the water pumping wells, the water treatment tank and tap water from
      households. Approximately 920 bp of the bacterial 16S rDNA were PCR-amplified,
      cloned, and sequenced for a total of 191 clones, which belonged to 112 unique
      phylotypes. The water of the pumping wells harbored a typical subsurface
      bacterial assemblage, with no human pathogens, dominated by beta-Proteobacteria.
      Cell abundance in the water treatment tank decreased significantly, close to
      detection limit, but bacterial diversity remained high. However, the dominance of
      beta-Proteobacteria decreased considerably, indicating the sensitivity of this
      group to drinking water disinfection treatment. Tap water from the households
      hosted a much less diverse, low-cell bacterial assemblage, dominated by
      Mycobacterium-like phylotypes, related to biofilm bacterial communities.

PMID- 19404755
TI  - Assessment of water quality parameters in the stream Galyan, Trabzon, Turkey.
AB  - This paper presents a comprehensive evaluation of drinking water quality from the
      stream Galyan and its tributary, the stream Kustul, in Trabzon Province, Turkey.
      In this study, surface water quality data for 20 physical and chemical parameters
      were determined and collected from three monitoring stations of the understudy
      stream during April 2004 to March 2005. According to the Turkish Water Pollution
      Control Regulation, the stream Galyan water was classified, and the studied
      parameters were evaluated for the values proposed by Turkish Standard (TS) 266
      and World Health Organization (WHO) guidelines. The results showed that TS 266
      and WHO guidelines were exceeded for Fe (up to 860 microg/l) and Cr (up to 134.7
      microg/l). Pearson's correlation was also used to determine the relationship of
      the studied parameters and as a result significant correlations were observed
      between some parameters.

PMID- 19404757
TI  - An approach for land suitability evaluation using geostatistics, remote sensing,
      and geographic information system in arid and semiarid ecosystems.
AB  - This study was undertaken to incorporate geostatistics, remote sensing, and
      geographic information system (GIS) technologies to improve the qualitative land
      suitability assessment in arid and semiarid ecosystems of Arsanjan plain,
      southern Iran. The primary data were obtained from 85 soil samples collected from
      tree depths (0-30, 30-60, and 60-90 cm); the secondary information was acquired
      from the remotely sensed data from the linear imaging self-scanner (LISS-III)
      receiver of the IRS-P6 satellite. Ordinary kriging and simple kriging with
      varying local means (SKVLM) methods were used to identify the spatial dependency
      of soil important parameters. It was observed that using the data collected from
      the spectral values of band 1 of the LISS-III receiver as the secondary variable
      applying the SKVLM method resulted in the lowest mean square error for mapping
      the pH and electrical conductivity (ECe) in the 0-30-cm depth. On the other hand,
      the ordinary kriging method resulted in a reliable accuracy for the other soil
      properties with moderate to strong spatial dependency in the study area for
      interpolation in the unstamped points. The parametric land suitability evaluation
      method was applied on the density points (150 x 150 m(2)) instead of applying on
      the limited representative profiles conventionally, which were obtained by the
      kriging or SKVLM methods. Overlaying the information layers of the data was used
      with the GIS for preparing the final land suitability evaluation. Therefore,
      changes in land characteristics could be identified in the same soil uniform
      mapping units over a very short distance. In general, this new method can easily
      present the squares and limitation factors of the different land suitability
      classes with considerable accuracy in arbitrary land indices.

PMID- 19404758
TI  - First recorded proliferation of Coolia monotis (Meunier, 1919) in the North Lake
      of Tunis (Tunisia) correlation with environmental factors.
AB  - Coolia monotis is a potentially toxic epiphytic dinoflagellate widespread along
      the Mediterranean coasts, where it is frequently detected year round at low
      concentrations. However, it only proliferates recurrently in some localities. The
      North Lake of Tunis is one of the affected areas in the southwestern part of the
      Mediterranean Sea. This site is one of the most productive aquatic Tunisian areas
      (Recreational Fisheries and shellfish collecting). In the south part of this area
      of study, recurrent C. monotis proliferation (5 x10(5) cells per liter) took
      place in late spring and early summer of 2006. During this proliferation, the
      spatial distribution of C. monotis species, phytoplankton community, and abiotic
      factors were studied. The composition of the phytoplankton community exhibited a
      clear dominance of dinoflagellates over other genera. We suggest that
      proliferation development of C. monotis was linked to climatic conditions, water
      temperature (r = 0.24, p < 0.05) and high concentrations of nitrogenous
      nutrients, essentially NH(4)(+) (r = 0.18, p < 0.05) and NO(3)(-) (r = 0.21, p <
      0.05).

PMID- 19404756
TI  - Monitoring pollution in Tunisian coasts using a scale of classification based on
      biochemical markers in worms Nereis (Hediste) diversicolor.
AB  - This paper aims to assess the marine environment quality along the Tunisian
      coasts using a statistical approach based on biomarkers response in the
      polychaete worms Nereis (Hediste) diversicolor. Worms were collected from six
      sites: Bizerta Lagoon, Gargour, Nakta, Mahres, Skhira and from Teboulba
      considered as a reference site. The biomarkers selected in this work were (1) the
      activities of cytochrome P450-dependent NADPH cytochrome c reductase (NADPH red)
      as phase I enzyme, (2) glutathione S-transferase as phase II enzyme and (3) the
      acetylcholinesterase activity as neurotoxicity marker. Oxidative stress was
      evaluated using catalase activity and malondialdehyde accumulation. For each
      biomarker, a discriminatory factor was calculated and a response index was
      allocated. For each site, a multi-marker pollution index was calculated as the
      sum of the response index of each of the five more discriminating biomarkers. The
      results show differences between sites compared with the reference samples. The
      multi-marker approach confirms that worms from Bizerta and Mahress have been
      submitted to highly polluted environment. Mahress shows the highest multi-marker
      pollution index, indicating a highly contamination status.

PMID- 19404759
TI  - Seasonal variation in physicochemical properties of coastal waters of Kalpakkam,
      east coast of India with special emphasis on nutrients.
AB  - A study pertaining to the seasonal variation in physicochemical properties of the
      coastal waters was carried out at Kalpakkam coast for a period of 1 year
      (February 2006 to January 2007). It revealed that the coastal water was
      significantly influenced by freshwater input during North East (NE) monsoon and
      post-monsoon periods. Concentration of all the nutrients and dissolved oxygen
      (DO) was relatively high during the NE monsoon, whereas, salinity and chlorophyll
      a (chl-a) were at their minimum level during this period. Phytoplankton
      production peak was observed in summer during which a typical marine condition
      prevailed. The present observed values of nitrate, phosphate, silicate, and
      turbidity are significantly high (five to ten times) compared to that of the pre
      Tsunami period from this coast. Relatively low DO and chl-a concentration was
      noticed during the post-Tsunami period. A notable feature of this study is that
      though nutrient concentration in the coastal waters during post-Tsunami period
      has increased significantly, turbidity, the most single dominating factor, was
      found to adversely affect the phytoplankton production during post-Tsunami period
      as reflected by relatively low chl-a concentration. Thus, the post-Tsunami period
      may result in a change in coastal biodiversity pattern concomitant with change in
      coastal water quality.

PMID- 19404760
TI  - Indoor and outdoor airborne bacteria in child day-care centers in Edirne City
      (Turkey), seasonal distribution and influence of meteorological factors.
AB  - This paper presents information about airborne mesophilic bacteria in the indoor
      and outdoor air of child day-care centers (CDCCs) in the city of Edirne, Turkey.
      Air samples were collected using the Petri plate gravitational settling method
      from the indoor and outdoor air of CDCCs. Counts of airborne bacteria were
      measured as colony forming units (CFU) collected by gravity onto Brain Heart
      Infusion Agar plates (with 5% sheep blood). Samples were taken monthly over a
      period of 12 months between January and December 2004. A total of 3,120 bacteria
      colonies were counted on 192 Petri plates. Four groups of culturable bacteria
      were identified: gram-positive cocci, gram-positive bacilli, endospore-forming
      gram-positive bacilli, and gram-negative bacteria. Airborne gram-positive
      bacteria were the most abundant at more than 95% of the measured population.
      While gram-positive cocci were more common in indoor environments, gram-positive
      bacilli were more dominant in outdoor air. Bacteria commonly isolated from CDCCs
      were identified at a genus level. Staphylococcus (39.16%), Bacillus (18.46%),
      Corynebacterium (16.25%), and Micrococcus (7.21%) were dominant among the genera
      identified in the present study. The dominant genera identified in the day-care
      centers were Staphylococcus, Micrococcus, and Corynebacterium for indoor air and
      Bacillus, Corynebacterium, and Staphylococcus for outdoor air. Staphylococcus,
      Streptococcus, Bacillus, and Corynebacterium genera were found in samples from
      every month. Bacterial colony counts were compared by sampling location (indoors
      and outdoors), seasons, and meteorological factors. We found negative
      correlations between the monthly total outdoor bacterial counts and the sampling
      day's average relative humidity and average rainfall, and the monthly average
      rainfall. Fluctuations in bacterial counts in different seasons were observed.

PMID- 19404761
TI  - Structural analysis of trypanosomal sirtuin: an insight for selective drug
      design.
AB  - The infectious disease burden imposed by trypanosomatidae family continues to
      create burden in countries that are least equipped to bring new medicines to the
      clinic. For sickness caused by this family of parasites (African trypanosomiasis,
      Chagas disease, and leishmaniasis) no vaccines are available, and currently
      available drugs suffer from insufficient efficacy, excessive toxicity, and steady
      loss of effectiveness due to resistance. Availability of the genome sequence of
      pathogens of this family offers a unique avenue for the identification of novel
      common drug targets for all three pathogens. Sirtuin family of nicotinamide
      adenine dinucleotide (NAD)-dependent deacetylases are remarkably conserved
      throughout evolution from archaebacteria to eukaryotes and plays an important
      role in trypanosomatidae biology and virulence. In order to gain insight for
      selective drug design, three-dimensional (3D) models of L. major, L. infantum, T.
      brucie, and T. cruzi sirtuin were constructed by homology modeling and compared
      with human sirtuin. The molecular electrostatic potentials and cavity depth
      analysis of these models suggest that the inhibitor binding catalytic domain has
      various minor structural differences in the active site of trypanosomal and human
      sirtuin, regardless of sequence similarity. These studies have implications for
      designing effective strategies to identify inhibitors that can be developed as
      novel broad-spectrum antitrypanosomal drugs.

PMID- 19404762
TI  - Evaluation of the cytogenetic damage induced by the organophosphorous insecticide
      acephate.
AB  - The organophosphorous insecticide acephate was tested for its ability to induce
      in vitro cytogenetic effect in human peripheral lymphocytes by using the
      chromosomal aberrations (CAs), sister chromatid exchange (SCE) and micronuclei
      (MN) assay. The level of nuclear DNA damage of acephate was evaluated by using
      the comet assay. Concentrations of 12.5, 25, 50, 100 and 200 mug mL(-1) of
      acephate were used. All concentrations of acephate induced significant increase
      in the frequency of CAs and in the formation of MN dose dependently (r = 0.92 at
      24 h, r = 0.95 at 48 h for CAs, r = 0.87 for MN). A significant increase was
      observed in induction of SCE at 50, 100 and 200 mug mL(-1) concentrations during
      24 h treatment and at all concentrations (except 12.5 mug mL(-1)) during 48 h
      treatment period in a dose-dependent manner (r = 0.84 at 24 h, r = 0.88 at 48 h).
      Acephate did not affect the replicative index and cytokinesis-block proliferation
      index (CBPI). However, it significantly decreased the mitotic index at all three
      highest concentrations (50, 100, 200 mug mL(-1)) for 24 h treatment and at all
      concentrations (except 12.5 mug mL(-1)) for 48 h treatment, dose-dependently (r =
      0.94 at 24 h, r = 0.92 at 48 h). A significant increase in mean comet tail length
      was observed at 100 and 200 mug mL(-1) concentrations compared with negative
      control in a concentration-dependent manner (r = 0.94). The mean comet tail
      intensity was significantly increased at only 200 mug mL(-1) concentration. The
      present results indicate that acephate is a clastogenic, cytotoxic agent and it
      causes DNA damage at high concentrations in human lymphocytes in culture.

PMID- 19404764
TI  - Testing coexistence and genetic containment for an autogamous crop.
AB  - Is there any risk that the threshold for admixture of genetically modified seeds
      in the harvest of a conventional cultivar, 0.9% in Europe, will be exceeded in
      the case of inbreeder crops? Using herbicide-resistant foxtail millet, Setaria
      italica, as a model of a preferentially autogamous crop, such as wheat and rice,
      field experiments show that genotype admixture due to pollen flow between
      adjacent fields is about 0.03% on average for the 10 adjacent meters, and 10
      times less in the next 20-m lane. In the case of a maternally inherited
      resistance gene, the admixture rate is at least 100 times lower. Recessive
      herbicide resistance has also been tested but would be efficient only if the
      agreed coexistence rules were based on phenotype detection.

PMID- 19404763
TI  - Generation of stable Xenopus laevis transgenic lines expressing a transgene
      controlled by weak promoters.
AB  - Combining two existing protocols of trangenesis, namely the REMI and the I-SceI
      meganuclease methods, we generated Xenopus leavis expressing a transgene under
      the control of a promoter that presented a restricted pattern of activity and a
      low level of expression. This was realized by co-incubating sperm nuclei, the I
      SceI enzyme and the transgene prior to transplantation into unfertilized eggs.
      The addition of the woodchuck hepatitis virus posttranscriptional regulatory
      element in our constructs further enhanced the expression of the transgene
      without affecting the tissue-specificity of the promoter activity. Using this
      combination of methods we produced high rates of fully transgenic animals that
      stably transmitted the transgene to the next generations with a transmission rate
      of 50% indicating a single integration event.

PMID- 19404765
TI  - Loss via peritoneal fluid as a factor for low 25(OH)D3 level in peritoneal
      dialysis patients.
AB  - BACKGROUND/AIMS: In patients with end-stage renal disease (ESRD), the 25
      hydroxyvitamin D3 (25(OH)D3) level is known to be lower compared to that of the
      normal population. In the present study, we evaluated the influences of dialysis
      methods on the serum 25(OH)D3 level in patients with ESRD who are treated with
      hemodialysis and peritoneal dialysis. METHODS: Thirty-nine peritoneal dialysis
      (PD), 49 hemodialysis (HD) patients, and 33 healthy controls were included in the
      present study. The mean HD period was 30.38 +/- 21.81 months and the mean PD
      period was 26.35 +/- 24.04 months. Serum samples from the HD and PD patients and
      healthy controls were examined in terms of 25(OH)D3, intact parathyroid hormone
      (iPTH), and other biochemical laboratory tests. Additionally, the 25(OH)D3 level
      in the peritoneal fluid was analyzed in the PD group. RESULTS: The mean 25(OH)D3
      levels in the control, HD, and PD groups were 26.63 +/- 10.89, 21.65 +/- 12.38,
      and 13.46 +/- 9.41 nmol/l, respectively (P < 0.001). The mean peritoneal fluid
      25(OH)D3 level was 28.53 +/- 7.66 nmol/l. Moreover, blood and PD fluid 25(OH)D3
      levels were 34 compared in the PD group. The 25(OH)D3 level in dialysate was
      higher than that of serum in PD patients (P < 0.001). CONCLUSION: The
      significantly lower blood levels of 25(OH)D3 in PD patients compared to those of
      HD patients were thought to be due to 25(OH)D3 loss via peritoneal fluid.

PMID- 19404766
TI  - Retrospective analysis of clinical profile prognostic factors and outcomes of 19
      patients of emphysematous pyelonephritis.
AB  - AIM: We aimed to study the clinical profile, prognostic factors, and the 6-month
      outcome of patients with emphysematous pyelonephritis (EPN) METHODS: All patients
      admitted with a diagnosis of emphysematous pyelonephritis between January 2001
      and July 2007 were included. RESULTS: Overall 19 cases were diagnosed to have
      emphysematous pyelonephritis. There were 16 females and three males. Fourteen
      cases had type 2 diabetes mellitus. Fourteen cases had unilateral involvement and
      five had bilateral involvement. Eleven cases were classified as having class 1 or
      2 disease and eight cases had class 3 and 4 disease. E. coli was the most common
      organism cultured (68.4%). Five cases underwent percutaneous drainage of the
      collecting system and three cases had nephrectomy of which 10.5% (two with
      advanced disease) expired. Shock at admission (p = 0.03), serum creatinine >5.0
      mg/dl (p = 0.035) and DIC (p = 0.017) were independent poor prognostic factors.
      There was no difference in the prognosis between patients who had >or=2 or <2
      poor prognostic factors (p = 0.16). However, prognosis was not related to disease
      class, unilateral vs. bilateral involvement, sepsis or the age of the patient. At
      6 months, two patients were on maintenance hemodialysis. CONCLUSIONS: In cases of
      EPN, shock, serum creatinine >5.0 mg/dl and DIC at admission are poor prognostic
      factors. Larger prospective studies are needed to confirm our findings.

PMID- 19404767
TI  - Extrapulmonary tuberculosis in a hemodialysis patient with unusual clinical
      presentation.
AB  - The incidence of active tuberculosis in patients undergoing maintenance dialysis
      for a long time is considerably higher than that in general population. A 39-year
      old male treated by hemodialysis three times a week for six months was admitted
      to the hospital with a painless mass palpable under his right areola. X-ray
      examination of chest showed a hyperintense lesion. Computed tomography revealed a
      cystic mass in the superior segment of inferior lobe near the thoracic vertebrae.
      Needle aspiration of the lesion revealed granulomas and acid-resistant bacteria.
      Anti-tuberculous therapy was therefore initiated. After eight months the patient
      was admitted back with paraplegia. Magnetic resonance imaging (MRI) revealed that
      the lesion defined by computed tomography (CT) was extending to the spinal duct
      and compressing the spinal cord. A tissue biopsy was performed and granulomas
      were identified. Mycobacterium tuberculosis grew in the culture. This case
      suggests that in areas with a high incidence of tuberculosis renal patients in a
      high-risk group should be examined periodically to exclude insidious infection
      and reduce morbidity and mortality.

PMID- 19404769
TI  - Construction and characterization of a cDNA library from head kidney of Japanese
      sea bass (Lateolabrax japonicus).
AB  - In this paper, a cDNA expression library from head kidney of Japanese sea bass
      (Lateolabrax japonicus) was constructed for the first time. The first-strand cDNA
      was synthesized with Moloney Murine Leukaemia virus reverse transcriptase and the
      double-stranded cDNA was digested by Xho I enzyme. Size fractionation was
      performed on CHROMA SPIN-400 columns. cDNA fragments longer than 500 bps were
      ligated into the lambdaZAPExpress vector. The recombinant DNA was packaged in
      vitro with Gigapack III gold packaging extract. The titers of the primary and
      amplified library were 1.0 x 10(5) and 5.0 x 10(9) pfu/ml, respectively. To
      characterize the constructed cDNA library, 15 phage plaques were selected
      randomly to test the inserted fragments. The results showed that the inserts were
      mostly longer than 500 bps. To test the utility, the library was screened with
      primers designed for three immune-related genes of, Myxovirus resistant (Mx),
      tumor necrosis factor-alpha (TNF-alpha) and Toll-like receptor (TLR). Results of
      Blastn and alignment showed that they are members of Mx, TNF-alpha and TLR gene
      families, respectively, which meets our anticipates for this cDNA library as an
      immune-related one. These results confirmed that the cDNA library constructed
      will provide a useful tool for gene cloning and expression analysis in immune
      system of Japanese sea bass.

PMID- 19404768
TI  - Ophiostomatoid fungi (Ascomycota) associated with Pinus tabuliformis infested by
      Dendroctonus valens (Coleoptera) in northern China and an assessment of their
      pathogenicity on mature trees.
AB  - Dendroctonus valens is an invasive pest in coniferous forests of northern China.
      It was suspected of being responsible for the death of more than three million
      Pinus tabuliformis trees. The present study sought to identify the ophiostomatoid
      fungi associated with D. valens in northern China and understand the possible
      role of these fungi in the pine decline. On the basis of morphology, physiology,
      mating compatibility and phylogenetic analyses of multiple DNA sequences, seven
      species of ophiostomatoid fungi were isolated from and around D. valens
      galleries: Leptographium alethinum, Grosmannia koreana (teleomorph of L.
      koreanum), L. procerum, L. sinoprocerum, L. truncatum, Pesotum aureum and P.
      pini. All have been recorded for the first time in China. Among them, the
      occurrence of the dominant species L. procerum is positively linked to attack
      intensities of D. valens. The pathogenicity of four species (L. koreanum, L.
      procerum, L. sinoprocerum and L. truncatum) was tested on mature P. tabuliformis
      trees by stem inoculation. All inoculated strains caused significant necrotic
      lesions on the inner bark. However, L. koreanum and L. truncatum induced more
      extensive lesions than L. procerum and L. sinoprocerum. Their association with D.
      valens and the P. tabuliformis decline is discussed.

PMID- 19404771
TI  - Questions never asked. Positive family outcomes of extremely premature
      childbirth.
AB  - OBJECTIVE: To explore positive aspects of family life after extremely premature
      childbirth, thereby supplementing current literature on long-term family outcome.
      DESIGN: Semi-structured, qualitative research interviews were analysed according
      to the editing strategy described by Miller and Crabtree. SETTING: Denmark,
      Europe. PARTICIPANTS: Nine fathers and 11 mothers of 14 children born before 28
      completed weeks of gestation at a tertiary centre were interviewed when their
      children were 7-10 years old. RESULTS: Whereas developmental delay, functional
      limitations, family burden, and parental distress are commonly used outcome
      measures, experiences of another nature were reported in the lives of survivors
      and their parents in our study. Thus, in spite of periods of deep distress and
      fear, periods of concern and anxiety and for some parents a workload far beyond
      average, parents' descriptions of their children's trajectories were also
      characterised by a perception of improvement and progress. Likewise, all parents
      reported much love and joy from child rearing. CONCLUSIONS: The value of these
      results may lie in the perspective they add to the interpretation of current
      research, the inspiration they may lend to future research on family outcome, as
      well as the balance they may offer in the information provided to parents of
      premature children.

PMID- 19404770
TI  - Contextualizing clinical research: the epistemological role of clinical
      equipoise.
AB  - Since its introduction in 1987, Benjamin Freedman's principle of clinical
      equipoise has enjoyed widespread uptake in bioethics discourse. Recent years,
      however, have witnessed a growing consensus that the principle is fundamentally
      flawed. One of the most vocal critics has undoubtedly been Franklin Miller. In a
      2008 paper, Steven Joffe and Miller build on this critical work, offering a new
      conception of clinical research ethics based on science, taking what they call a
      "scientific orientation" toward the ethics of clinical research. Though there is
      much to recommend Joffe and Miller's scientifically oriented conception of
      clinical research ethics, I believe that both the critical and constructive
      projects suffer from the same basic mistake: inattention to context. The internal
      norms of science cannot be fully specified, let alone satisfied, independently of
      contextual (external) factors that only come into view when we are attentive to
      the particular context of that form of inquiry.

PMID- 19404772
TI  - Life events and oral-health-related quality of life among young adults.
AB  - PURPOSE: Life-course approaches to understanding the determinants of health have
      led to a greater focus on the effects of life events on health. Life events may
      be construed as either positive or negative, and may have differential health
      effects. The aims of the study were to assess the association of positive and
      negative life events with oral-health-related quality of life (OHRQoL). METHODS:
      In 2005-2006, 1,859 study participants aged around 30 years old were surveyed by
      mailed self-complete questionnaire and invited to attend a dental examination.
      Data collected included life events, social support (MSPSS) and OHRQoL (OHIP-14).
      A total of 632 people responded (43% response). RESULTS: Multivariate analysis
      controlling for sex, education, income, dental behaviour and social support
      showed that the lower (OR = 0.4, 0.2-0.6) and middle tertiles (OR = 0.6, 0.4-0.9)
      for negative life events were associated with lower prevalence of problems
      related to OHRQoL compared to the higher tertile. CONCLUSIONS: OHRQoL among young
      adults was associated with negative life events, but not positive life events.
      This suggests that negative life events involving social readjustment need to
      considered as determinants of health in life-course oral epidemiology frameworks.

PMID- 19404773
TI  - Viability and cell cycle analysis of equine fibroblasts cultured in vitro.
AB  - This experiment aimed to study equine fibroblasts in culture analyzing and the
      cell cycle and viability of cells pre- and post-freezing. Skin fragments were
      obtained from 6 horses and cultured in DMEM high glucose + 10% FCS in 5% CO(2)
      until the beginning of confluence. Two passages were performed before freezing.
      Cells subjected to serum starvation (0.5% FCS) were analyzed for viability and
      cell cycle at 24, 48, 72, 96, 120, 144 and 168 h of culture. For the confluent
      groups, cells were analyzed at the moment they achieved confluence. Cellular
      viability was assisted with Hoescht 33342 and propidium iodide. The analysis of
      apoptosis/necrosis and cell cycle was performed using a flow cytometer (FACS
      Calibur BD((R))) after staining the cells with annexin V and propidium iodide.
      Both optical microscopy and flow cytometry confirmed that cellular viability was
      similar for serum starvation and confluent groups (average 84%). Similarly, both
      methods were efficient to synchronize the cell cycle before freezing. However,
      after thawing, serum starvation, for more than 24 h, was superior to culture for
      synchronizing cells in G0/G1 (69% x 90%). The results of this experiment indicate
      that equine fibroblasts can be efficiently cultured after thawing.

PMID- 19404774
TI  - Childhood predictive genetic testing for Li-Fraumeni syndrome.
AB  - Presymptomatic genetic testing in childhood for adult onset conditions is
      generally discouraged as it does not directly benefit the child and removes their
      autonomy. In certain cancer prone conditions such as Familial Adenomatous
      Polyposis and Von Hippel Lindau disease there are risks of disease in childhood
      and benefit to children not inheriting a mutation in being able to forego
      unpleasant screening tests. Li-Fraumeni syndrome caused by constitutional TP53
      mutations there are also implications in childhood with a risk of around 20% of a
      childhood malignancy. However, as yet no evidence based surveillance programme
      has been identified. We describe our experience of childhood testing for four
      children in two Li-Fraumeni families caused by TP53 mutations.

PMID- 19404775
TI  - Basal and inducible expression of the thiol-sensitive ART2.1 ecto-ADP
      ribosyltransferase in myeloid and lymphoid leukocytes.
AB  - ADP-ribosylation of cell surface proteins in mammalian cells is a post
      translational modification by which ecto-ADP-ribosyltransferases (ARTs) transfer
      ADP-ribose from extracellular NAD to protein targets. The ART2 locus at murine
      chromosome 7 encompasses the tandem Art2a and Art2b genes that encode the
      distinct ART2.1 and ART2.2 proteins. Although both ecto-enzymes share 80%
      sequence identity, ART2.1 activity is uniquely regulated by an allosteric
      disulfide bond that is reducible in the presence of extracellular thiols, such as
      cysteine and glutathione, that accumulate in hypoxic and ischemic tissues.
      Previous studies have characterized the expression of ART2.1 and ART2.2 in murine
      T lymphocytes but not in other major classes of lymphoid and myeloid leukocytes.
      Here, we describe the expression of ART2.1 activity in a wide range of freshly
      isolated or tissue-cultured murine myeloid and lymphoid leukocytes. Spleen
      derived macrophages, dendritic cells (DC), and B cells constitutively express
      ART2.1 as their predominant ART while spleen T cells express both ART2.1 and the
      thiol-independent ART2.2 isoform. Although bone-marrow-derived macrophages (BMDM)
      and dendritic cells (BMDC) constitutively express ART2.1 at low levels, it is
      markedly up-regulated when these cells are stimulated in vitro with IFNbeta or
      IFNgamma. ART2.1 expression and activity in splenic B cells is modestly up
      regulated during incubation in vitro for 24 h, a condition that promotes B cell
      apoptosis. This increase in ART2.1 is attenuated by IL-4 (a B cell survival
      factor), but is not affected by IFNbeta/gamma, suggesting a possible induction of
      ART2.1 as an ancillary response to B cell apoptosis. In contrast, ART2.1 and
      ART2.2, which are highly expressed in freshly isolated splenic T cells, are
      markedly down-regulated when purified T cells are incubated in vitro for 12-24 h.
      Studies with the BW5147 mouse thymocyte line verified basal expression of ART2.1
      and ART2.2, as in primary spleen T cells, and demonstrated that both isoforms can
      be up-regulated when T cells are maintained in the presence of IFNs. Comparison
      of the surface proteins which are ADP-ribosylated by ART2.1 in the different
      leukocyte subtypes indicated both shared and cell-specific proteins as ART2.1
      substrates. The LFA-1 integrin, a major target for ART2.2 in T cells, is also ADP
      ribosylated by the ART2.1 expressed in macrophages. Thus, ART2.1, in contrast to
      ART2.2, is expressed in a broad range of myeloid and lymphoid leukocytes. The
      thiol redox-sensitive nature of this ecto-enzyme suggests an involvement in
      purinergic signaling that occurs in the combined context of inflammation and
      hypoxia/ischemia.

PMID- 19404777
TI  - Triggers of the HSP70 stress response: environmental responses and laboratory
      manipulation in an Antarctic marine invertebrate (Nacella concinna).
AB  - The Antarctic limpet, Nacella concinna, exhibits the classical heat shock
      response, with up-regulation of duplicated forms of the inducible heat shock
      protein 70 (HSP70) gene in response to experimental manipulation of seawater
      temperatures. However, this response only occurs in the laboratory at
      temperatures well in excess of any experienced in the field. Subsequent
      environmental sampling of inter-tidal animals also showed up-regulation of these
      genes, but at temperature thresholds much lower than those required to elicit a
      response in the laboratory. It was hypothesised that this was a reflection of the
      complexity of the stresses encountered in the inter-tidal region. Here, we
      describe a further series of experiments comprising both laboratory manipulation
      and environmental sampling of N. concinna. We investigate the expression of HSP70
      gene family members (HSP70A, HSP70B, GRP78 and HSC70) in response to a further
      suite of environmental stressors: seasonal and experimental cold, freshwater,
      desiccation, chronic heat and periodic emersion. Lowered temperatures (-1.9
      degrees C and -1.6 degrees C), generally produced a down-regulation of all HSP70
      family members, with some up-regulation of HSC70 when emerging from the winter
      period and increasing sea temperatures. There was no significant response to
      freshwater immersion. In response to acute and chronic heat treatments plus
      simulated tidal cycles, the data showed a clear pattern. HSP70A showed a strong
      but very short-term response to heat whilst the duplicated HSP70B also showed
      heat to be a trigger, but had a more sustained response to complex stresses.
      GRP78 expression indicates that it was acting as a generalised stress response
      under the experimental conditions described here. HSC70 was the major chaperone
      invoked in response to long-term stresses of varying types. These results provide
      intriguing clues not only to the complexity of HSP70 gene expression in response
      to environmental change but also insights into the stress response of a non-model
      species.

PMID- 19404778
TI  - The expression and prognosis of FOXO3a and Skp2 in human hepatocellular
      carcinoma.
AB  - The forkhead box proteins (FOXO proteins) comprise a large family of functionally
      diverse transcription factors involved in cellular proliferation, transformation,
      differentiation and longevity. Recently, ubiquitination and proteasome
      degradation of FOXO3a have been reported. In this study, we investigated the role
      of FOXO3a and Skp2 in human hepatocellular carcinoma progression.
      Immunohistochemical analysis was performed on formalin-fixed paraffin sections of
      91 specimens. Furthermore in vitro, western-blot analysis and protein
      stabilization studies were used to study the relationship between FOXO3a and
      Skp2. We found that the expression of FOXO3a was negatively related with Skp2
      expression (r = -0.583; p < 0.05) and FOXO3a expression correlated significantly
      with histological grade (p = 0.000), cirrhosis (p = 0.015), and tumor size (p =
      0.043) while Skp2 expression correlated significantly with histological grade (p
      = 0.000) and tumor size (p = 0.005). Kaplan-Meier analysis revealed that survival
      curves of low versus high expressers of FOXO3a and Skp2 showed a highly
      significant separation in HCC (p < 0.01). Our results suggested that FOXO3a and
      Skp2 may be considered to be important prognosis in human hepatocellular
      carcinoma. In vitro studies suggested that the degradation of FOXO3a may
      dependent on the expression of Skp2 in the proliferated Huh7 cells.

PMID- 19404779
TI  - Identification of chaulmoogric acid as a small molecule activator of protein
      phosphatase 5.
AB  - Protein phosphatase 5 (PP5) is an important protein phosphatase that is
      abundantly expressed in the central nervous system. Recent studies showed that
      PP5 activity in the neocortex from patients with Alzheimer's disease (AD) is
      decreased significantly, suggesting that small molecule PP5 activator may have
      therapeutic potential for AD. We performed a biochemical screening for PP5
      activators with the microsource compound library. Chaulmoogric acid was
      identified to be an effective activator with EC(50) value of 134.5 microM.
      Importantly, results from circular dichroism (CD) and limited proteolysis study
      showed that chaulmoogric acid binds to a region of tetratricopeptide repeat (TPR)
      domain of PP5 resulting in complete loss of helical contents. These results
      demonstrate a different mechanism of action from that of arachidonic acid, a
      known activator for PP5 dephosphorylation activity. Synergistic activation of PP5
      enzymatic activity was also observed with combined application of both compounds
      at relatively low concentrations. Therefore, further structure activity
      relationship study of chaulmoogric acid may facilitate the discovery of small
      molecules that can synergize with endogenous arachidonic acid for PP5 activation.

PMID- 19404780
TI  - The new application of biosorption properties of Enteromorpha prolifera.
AB  - The main goal of this paper was to elaborate the possibility of industrial
      application of biosorption properties of Enteromorpha prolifera (production of
      mineral feed additives for livestock). In this study, biosorption process was
      used in the binding of chromium(III) ions from aqueous solution by the green
      macroalga. The kinetics of biosorption process was studied in a batch system with
      respect to the initial pH, temperature, initial metal ion concentration, and
      initial biomass concentration. E. prolifera demonstrated good biosorption
      properties. The equilibrium biosorption capacity increased with pH and with
      initial concentration of metal ions. The uptake of chromium(III) ions by the
      dried alga was affected by the temperature, but in small extent. With increase of
      the biomass concentration, the decrease of biosorption capacity at equilibrium
      was observed. The best biosorption conditions were determined as the initial pH
      5, temperature 25 degrees Celsius, the initial chromium(III) ions concentration
      400 mg/L, and biosorbent concentration 1.0 g/L. Biosorption capacity at
      equilibrium reached at these conditions was 100 mg/g. The mechanism of the
      biosorption of chromium(III) ions by E. prolifera was analyzed in equilibrium
      experiments. Equilibrium data were fitted to Langmuir, Dubinin-Radushkevich, and
      Freundlich adsorption isotherms. The most suitable model for describing the
      obtained data was Langmuir model. The experimental results and the analysis of
      the solution before and after biosorption process suggested ion-exchange
      mechanism.

PMID- 19404781
TI  - Heterologous expression and characterization of an endoglucanase from a symbiotic
      protist of the lower termite, Reticulitermes speratus.
AB  - RsSymEG, an endoglucanase of glycosyl hydrolase family (GHF) 7 encoded by a
      transcript isolated from the symbiotic protist of the termite Reticulitermes
      speratus, is expressed in Aspergillus oryzae. Interestingly, purified RsSymEG1
      has a relatively higher specific activity (603 micromol min(-1) mg(-1) protein)
      and V(max) value (769.6 unit/mg protein) than previously reported data for GHF7
      endoglucanase of Trichoderma ressei. It also has the same K(m) value (1.97 mg/ml)
      with Clostridium cellulolyticum enzymes that contain cellulose binding module, a
      property indicative of high affinity to substrate, though no cellulose binding
      module is found within it. Thin-layer chromatography analysis revealed that
      RsSymEG1 preferentially hydrolyzes the beta-1,4-cellulosic linkage of
      cellodextrins into cellobiose and glucose.

PMID- 19404782
TI  - Overlapping features of eclampsia and postpartum angiopathy.
AB  - INTRODUCTION: Postpartum cerebral angiopathy (PPA) is considered one of a diverse
      group of rare conditions termed "reversible cerebral vasoconstriction syndromes".
      Existing literature suggest considerable overlap in the manifestations of
      eclampsia and PPA. METHODS: Retrospective case series review of PPA and eclampsia
      from a single neurosciences intensive care unit patient log identified over a
      consecutive 18-month period. A MEDLINE search (using OVID) of the English
      literature from 1950 through October 2008 was also performed. RESULTS: Four
      patients who meet the obstetrical criteria for eclampsia and four patients whose
      clinical and radiographic features were consistent with PPA were identified.
      Twenty-eight patients with PPA were identified from the literature and showed
      significant clinical and radiographic overlap without cohort. CONCLUSION: Given
      the overlapping clinical, laboratory, and radiographical features of eclampsia
      and PPA, it is probable they share a similar underlying pathophysiological
      mechanism and represent different clinical expressions of the same pregnancy
      related disorder. The obstetrical definition of eclampsia may be to strict when
      applied in the neurosciences intensive care unit.

PMID- 19404783
TI  - Low-dose and high-dose synacthen tests and the hemodynamic response to
      hydrocortisone in acute traumatic brain injury.
AB  - INTRODUCTION: In order to identify whether low-dose (1 microg) tetracosactide
      (Synacthen) testing may be preferable to high-dose (250 microg) testing in the
      diagnosis of adrenal insufficiency in traumatic brain injury (TBI), as suggested
      by studies in other forms of critical illness. METHODS: We retrospectively
      reviewed the results of modified tetracosactide tests (involving administration
      of both low-dose and high-dose tetracosactide) conducted for clinical indications
      in patients in a neurocritical care unit within 10 days of TBI. Sixty-three
      modified tests were included and cortisol concentrations before and after
      administration of tetracosactide were extracted from the hospital records. Data
      were also extracted regarding hemodynamic response to empirical corticosteroid
      therapy, based on rapid weaning from vasoactive drugs. RESULTS: Cortisol
      increments at 30 and 60 min following tetracosactide correlated well in the low
      dose test (r(2) = 0.875, P < 0.0001). The mean cortisol concentration was 581
      nmol/l at 30 min and 556 nmol/l at 60 min in the low-dose test. Cortisol
      increments following low-dose and high-dose testing correlated well overall (r(2)
      = 0.839, P < 0.0001), but results were discordant in 27 of 63 cases (43%) when
      the same diagnostic threshold was used. ROC curve analysis showed that both tests
      performed poorly in identifying hemodynamic steroid responsiveness (AUC 0.553 and
      0.502, respectively). CONCLUSIONS: In the low-dose tetracosactide test, it is
      sufficient to determine cortisol concentrations at baseline and at 30 min. Low
      dose and high-dose tests give discordant results in a significant proportion of
      cases when using the same diagnostic threshold. Neither test can be used to guide
      the initiation of corticosteroid therapy in acute TBI.

PMID- 19404791
TI  - The uterine cervix and the importance of cervical secretions.

PMID- 19404784
TI  - 4-Nitrophenol isolated from diesel exhaust particles disrupts regulation of
      reproductive hormones in immature male rats.
AB  - In previous studies, we found that 4-nitrophenol (PNP) isolated from diesel
      exhaust particles exhibited both estrogenic and anti-androgenic activities. This
      compound is also a degradation product of the insecticide parathion. Here, we
      investigated the in vivo effect of PNP on reproductive function in immature male
      rats. Twenty-eight-day-old rats were injected subcutaneously with PNP (0.01, 0.1,
      1, or 10 mg/kg) daily for 14 days. Plasma concentrations of luteinizing hormone
      (LH) were significantly lower in all PNP dosage groups than in the control group,
      and follicle-stimulating hormone (FSH) was significantly decreased in rats
      treated with 0.1, 1, or 10 mg/kg PNP. However, plasma concentrations of
      testosterone were significantly increased by 10 mg/kg PNP, and plasma
      concentrations of immunoreactive (ir)-inhibin were also significantly increased
      in the 0.1, 1, and 10 mg/kg PNP groups. Plasma concentrations of prolactin were
      significantly increased by 10 mg/kg PNP, and plasma concentrations of
      corticosterone were significantly increased in all treatment groups. These
      findings clearly show that PNP influences the hypothalamic-pituitary-gonadal axis
      in immature male rats, with decreased secretion of LH and FSH and increased
      secretion of testosterone and inhibin. PNP, therefore, appears to disrupt
      endocrine activity in the immature male reproductive system.

PMID- 19404792
TI  - In vitro influence of stem surface finish and mantle conformity on pressure
      generation in cemented hip arthroplasty.
AB  - BACKGROUND AND PURPOSE: Under physiological loads, debonded cemented femoral
      stems have been shown to move within their cement mantle and generate a fluid
      pump that may facilitate peri-prosthetic osteolysis by pressurizing fluid and
      circulating wear debris. The long-term physiological loading of rough and
      polished tapered stems in vitro has shown differences in performance, with
      greater interface pressures generated by the rough stems. In this study we
      investigated the individual effects of stem surface finish, degree of mantle
      wear, and mode of loading on the stem pump mechanism. METHOD: Rough and polished
      stems were loaded under different regimes in artificially worn cement mantles
      that permitted either 2 or 5 degrees of rotational stem movement, and the
      interface pressures were compared. RESULTS: The pressures generated by the rough
      and polished stems were similar in either type of mantle. The pattern of pressure
      generation in the 2-degree mantles was similar to the pressures generated by
      rough stems after long-term loading, but the high posterior wall pressures fell
      and the tip pressures increased in the 5-degree mantles. The torsional loads were
      principal drivers of pressure generation in all areas of the interface other than
      the implant tip, where axial loading predominated. INTERPRETATION: Femoral stems
      with rotational instability under cyclic torsional loads generate elevated
      interface fluid pressures and flows independently of stem surface finish. The
      rough surface finish is only important in creating this instability in tapered
      stems.

PMID- 19404793
TI  - In vitro comparison of the effects of rough and polished stem surface finish on
      pressure generation in cemented hip arthroplasty.
AB  - BACKGROUND AND PURPOSE: High pressures around implants can cause bone lysis and
      loosening. We investigated how pressures are generated around cemented femoral
      stems. METHOD: We compared the pressures generated by rough and polished tapered
      stems at their cement interfaces, in an in vitro model, before and after 1
      million load cycles. RESULTS: At the start of the study, the loading of both
      polished and rough stems generated interface pressures that were not
      statistically significantly different. After 1 million load cycles, the rough
      stems generated greater interface pressures than at the start (p = 0.03), with
      maximum pressure wave amplitudes of 450,000 Pa or 3,375 mm Hg. The pressures
      generated by polished stems were similar before and after 1 million load cycles,
      and were lower than the pressures generated by the rough stems (p = 0.01). Stem
      loading caused micromotion between the stem and cement. Polished stems migrated
      distally in the cement but retained rotational and axial stability. The rough
      stems also migrated distally and wore the cement mantle, leading to increased
      rotational instability. INTERPRETATION: The change in the rotational micromotion
      of the rough stem is likely to be the principal cause of the increased stem pump
      output and to be a key factor in the longevity of cemented femoral implants.

PMID- 19404794
TI  - Impaction bone grafting of the acetabulum at hip revision using a mix of bone
      chips and a biphasic porous ceramic bone graft substitute.
AB  - BACKGROUND AND PURPOSE: One of the greatest problems of revision hip arthroplasty
      is dealing with lost bone stock. Good results have been obtained with impaction
      grafting of allograft bone. However, there have been problems of infection,
      reproducibility, antigenicity, stability, availability of bone, and cost. Thus,
      alternatives to allograft have been sought. BoneSave is a biphasic porous ceramic
      specifically designed for use in impaction grafting. BoneSave is 80% tricalcium
      phosphate and 20% hydroxyapatite. Previous in vitro and in vivo studies have
      yielded good results using mixtures of allograft and BoneSave, when compared with
      allograft alone. This study is the first reported human clinical trial of
      BoneSave in impaction grafting. METHODS: We performed a single-institution, multi
      surgeon, prospective cohort study. 43 consecutive patients underwent revision hip
      arthroplasty using BoneSave and allograft to restore missing bone in the
      acetabulum. 9 patients had cemented acetabular components implanted and 34
      uncemented. 10 patients had cemented femoral components implanted and 1 had an
      uncemented femoral component. 32 patients did not have their femoral component
      revised. RESULTS: No patients were lost to follow-up. At a mean follow-up of 24
      (11-48) months, there were no re-revisions and there was no implant migration. 1
      acetabular component had confluent lucent lines at the implant-graft interface.
      Complications were rare (1 fracture, 2 dislocations). Patient satisfaction with
      the procedure was high. INTERPRETATION: Short-term results indicate that
      impaction grafting of BoneSave and allograft is an effective method of dealing
      with loss of bone stock at revision hip surgery.

PMID- 19404796
TI  - Is wear debris responsible for failure in alumina-on-alumina implants?
AB  - BACKGROUND AND PURPOSE: Ceramic-on-ceramic articulation is an attractive
      alternative to metal-on-polyethylene (PE) bearings, but little is known about the
      in vivo effects induced by dissemination of alumina wear debris in the
      periprosthetic tissues. We hypothesized that wear debris is not the main factor
      responsible for loosening and failure of the implant but that mechanical problems
      caused by incorrect surgical technique, prosthetic design, or trauma, may cause
      instability of the implants and result in production of wear debris. PATIENTS AND
      METHODS: Clinical, radiographic, laboratory, and microbiological data from 30
      consecutive patients with failed alumina-on-alumina arthroplasties, 19 with
      screwed socket and 11 with press-fit socket, were systematically collected and
      evaluated. Retrieved peri-implant tissues and prosthesis wear were also analyzed.
      RESULTS AND INTERPRETATION: Loosening was due to malpositioning, primary
      mechanical instability, trauma, or infection. Bone stock was generally preserved,
      even if screwed implants showed higher levels of osteolysis. Variable implant
      wear and tissue macrophage reaction were present but activation of giant
      cells/osteoclasts was not induced, and no correlation between histocytic reaction
      and the level of osteolysis was found. These findings indicate that, in contrast
      to the situation with metal-on-PE bearings, wear debris and occasional osteolysis
      were the effect rather than the cause of failure of ceramic-on-ceramic implants,
      and that press-fit socket fixation was the socket fixation design of preference.

PMID- 19404795
TI  - Three-dimensional mechanical evaluation of joint contact pressure in 12
      periacetabular osteotomy patients with 10-year follow-up.
AB  - BACKGROUND AND PURPOSE: Because of the varying structure of dysplastic hips, the
      optimal realignment of the joint during periacetabular osteotomy (PAO) may differ
      between patients. Three-dimensional (3D) mechanical and radiological analysis
      possibly accounts better for patient-specific morphology, and may improve and
      automate optimal joint realignment. PATIENTS AND METHODS: We evaluated the 10
      year outcomes of 12 patients following PAO. We compared 3D mechanical analysis
      results to both radiological and clinical measurements. A 3D discrete-element
      analysis algorithm was used to calculate the pre- and postoperative contact
      pressure profile within the hip. Radiological angles describing the coverage of
      the joint were measured using a computerized approach at actual and theoretical
      orientations of the acetabular cup. Quantitative results were compared using
      postoperative clinical evaluation scores (Harris score), and patient-completed
      outcome surveys (q-score) done at 2 and 10 years. RESULTS: The 3D mechanical
      analysis indicated that peak joint contact pressure was reduced by an average
      factor of 1.7 subsequent to PAO. Lateral coverage of the femoral head increased
      in all patients; however, it did not proportionally reduce the maximum contact
      pressure and, in 1 case, the pressure increased. This patient had the lowest 10
      year q-score (70 out of 100) of the cohort. Another hip was converted to hip
      arthroplasty after 3 years because of increasing osteoarthritis. INTERPRETATION:
      The 3D analysis showed that a reduction in contact pressure was theoretically
      possible for all patients in this cohort, but this could not be achieved in every
      case during surgery. While intraoperative factors may affect the actual surgical
      outcome, the results show that 3D contact pressure analysis is consistent with
      traditional PAO planning techniques (more so than 2D analysis) and may be a
      valuable addition to preoperative planning and intraoperative assessment of joint
      realignment.

PMID- 19404797
TI  - Outcome and serum ion determination up to 11 years after implantation of a
      cemented metal-on-metal hip prosthesis.
AB  - BACKGROUND AND PURPOSE: Little is known about the long-term outcome of cemented
      metal-on-metal hip arthroplasties. We evaluated a consecutive series of metal-on
      metal polyethylene-backed cemented hip arthroplasties implanted in patients under
      60 years of age. METHODS: 109 patients (134 joint replacements) were followed
      prospectively for mean 9 (7-11) years. The evaluation included clinical score,
      radiographic assessment, and blood sampling for ion level determination. RESULTS:
      At the final review, 12 hips had been revised, mainly because of aseptic
      loosening of the socket. Using revision for aseptic loosening as the endpoint,
      the survival rate at 9 years was 91% for the cup and 99% for the stem. In
      addition, 35 hips showed radiolucent lines at the bone-cement interface of the
      acetabulum and some were associated with osteolysis. The median serum cobalt and
      chromium levels were relatively constant over time, and were much higher than the
      detection level throughout the study period. The cobalt level was 1.5 microg/L 1
      year after implantation, and 1.44 microg/L 9 years after implantation.
      INTERPRETATION: Revisions for aseptic loosening and radiographic findings in the
      sockets led us to halt metal-on-metal-backed polyethylene cemented hip
      arthroplasty procedures. If the rigidity of the cemented socket is a reason for
      loosening, excessive release of metal ions and particles may be involved. Further
      investigations are required to confirm this hypothesis and to determine whether
      subluxation, microseparation, and hypersensitivity also play a role.

PMID- 19404798
TI  - Bipolar cemented hip hemiarthroplasty in patients with femoral neck fracture who
      are on hemodialysis is associated with risk of stem migration.
AB  - BACKGROUND AND PURPOSE: Femoral neck fractures are considerably more common in
      patients on hemodialysis than in the general population. We determined the
      outcome of bipolar hemiarthroplasty for hip fracture in patients with long-term
      hemodialysis and compared it with that of a matched-paired group of patients with
      intact renal function. METHODS: We analyzed 26 bipolar hemiarthroplasties in 23
      hemodialysed patients with a mean age of 56 (41-78) years who were followed for
      mean 3.6 (1-8) years. These cases were matched for age, sex, and BMI with 26
      patients with femoral neck fractures and normal renal function. The mean follow
      up time in the control group was 7 (5-10) years. As primary surgery for their
      femoral neck fracture, all patients had a bipolar hemiarthroplasty with a 28-mm
      metal-polyethylene internal articulation and a cemented stem. RESULTS: The
      mortality rate was 21% in the hemodialysed group and 4% in the control group (p =
      0.005). The bipolar head migrated in 1 patient in the hemodialysed group but in
      none of the patients in the case-matched group. In the hemodialysed group, 8
      stems migrated and 3 of these were revised, whereas in the control group 3 stems
      migrated and 2 were revised. The stem migration in the hemodialysed group was not
      preceded by the development of osteolysis or radiolucent lines at the bone-cement
      interface. The cumulative survival for prosthesis migration as endpoint was 44%
      at 5 years in the hemodialysed group and 96% in the control group (p = 0.03).
      INTERPRETATION: The main mode of failure of cemented bipolar hemiarthroplasties
      in hemodialysed patients is stem migration, due to failure of the bone-cement
      interface.

PMID- 19404799
TI  - Bone healing of severe acetabular defects after revision arthroplasty.
AB  - BACKGROUND AND PURPOSE: Healing of acetabular bone grafts may be difficult to
      assess in conventional radiographs. We used PET to analyze healing of morselized
      bone allografts, impacted in large osteolytic acetabular defects at revision
      arthroplasty. PATIENTS AND METHODS: 7 cases had a cup revision because of
      loosening, with repair of a segmental defect using a perforated, wide and thin
      plate. The osteolytic acetabulum was impacted with morselized bone allograft
      before cementing a polyethylene cup. [(18)F]-fluoride PET scans were used to
      monitor bone healing inside the graft bed 1 week, 4 weeks, and 12 months after
      surgery. The contralateral pelvic bone above the acetabulum was used as
      reference. A second group of 4 cases was analyzed for bone-forming activity in
      the state of mechanical loosening of an acetabular component of a THA. RESULTS:
      Preoperatively, the uptake was raised by 64% compared to the reference. 1 week
      after surgery it was increased by 77% in segmental regions, while the uptake was
      at the reference level in cavitary regions. After 4 months the uptake was
      increased by 91% in cavitary regions and by 117% in segmental regions. 1 year
      after surgery, the increase in uptake was 20% in both regions. All implants were
      stable on radiographs. INTERPRETATION: We found PET to be a sensitive and useful
      method for evaluation of the spatial and temporal development of bone formation.

PMID- 19404800
TI  - Dislocation of total hip replacement in patients with fractures of the femoral
      neck.
AB  - BACKGROUND: Total hip replacement is increasingly used in active, relatively
      healthy elderly patients with fractures of the femoral neck. Dislocation of the
      prosthesis is a severe complication, and there is still controversy regarding the
      optimal surgical approach and its influence on stability. We analyzed factors
      influencing the stability of the total hip replacement, paying special attention
      to the surgical approach. PATIENTS AND METHODS: We included 713 consecutive hips
      in a series of 698 patients (573 females) who had undergone a primary total hip
      replacement (n = 311) for a non-pathological, displaced femoral neck fracture
      (Garden III or IV) or a secondary total hip replacement (n = 402) due to a
      fracture-healing complication after a femoral neck fracture. We used Cox
      regression to evaluate factors associated with prosthetic dislocation after the
      operation. Age, sex, indication for surgery, the surgeon's experience, femoral
      head size, and surgical approach were tested as independent factors in the model.
      RESULTS: The overall dislocation rate was 6%. The anterolateral surgical approach
      was associated with a lower risk of dislocation than the posterolateral approach
      with or without posterior repair (2%, 12%, and 14%, respectively (p < 0.001)).
      The posterolateral approach was the only factor associated with a significantly
      increased risk of dislocation, with a hazards ratio (HR) of 6 (2-14) for the
      posterolateral approach with posterior repair and of 6 (2-16) without posterior
      repair. INTERPRETATION: In order to minimize the risk of dislocation, we
      recommend the use of the anterolateral approach for total hip replacement in
      patients with femoral neck fractures.

PMID- 19404801
TI  - High hip center bipolar hemiarthroplasty for non-reconstructable pelvic
      discontinuity.

PMID- 19404802
TI  - Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip
      spacers in vivo.
AB  - BACKGROUND AND PURPOSE: Late infections after total hip arthroplasty are still a
      problem. Treatment procedures include resection arthroplasty with implantation of
      antibiotic-loaded beads or implantation of an antibiotic-impreganted spacer.
      However, little is known about antibiotic elution from bone cement beyond the
      first 2-3 postoperative days in humans. METHODS: 17 hip spacers (80 g PMMA, 1g
      gentamicin, and 4 g vancomycin) and 11 chains (40 g PMMA, 0.5 g gentamicin, and 2
      g vancomycin) in 28 patients were studied. The release of both agents was
      measured in the drainage fluid on a daily basis. The drains were left in situ
      until less than 50 mL was produced per day. The elution of both antibiotics was
      determined by fluorescence polarization immunoassay. Systemic antibiotics were
      given postoperatively according to antibiogram. If possible, no gentamicin or
      vancomycin was given. RESULTS: Peak mean concentrations from beads and spacers
      were reached for gentamicin (1,160 (12-371) microg/mL and 21 (0.7-39) microg/mL,
      respectively) and for vancomycin (80 (21-198) microg/mL and 37 (3.3-72)
      microg/mL) on day 1. The last concentrations to be determined were 3.7 microg/mL
      gentamicin and 23 microg/mL vancomycin in the beads group after 13 days, and 1.9
      microg/mL gentamicin and 6.6 microg/mL vancomycin in the spacer group after 7
      days. Between the fifth and seventh day, an intermittent increase in elution of
      vancomycin from both beads and spacers and of gentamicin from spacers was
      noticed. No renal or hepatic dysfunction was observed. INTERPRETATION: Beads
      showed higher elution characteristics in vivo than the spacers due to their
      larger surface area; however, a great amount of inter-subject variability was
      seen for both beads and spacers. The inferior elution properties of spacers
      emphasize the importance of additional systemic antibiotics for this treatment
      procedure during the postoperative period. Future studies should clarify whether
      the dose of antibiotics or length of antibiotic therapy may be reduced in the
      case of bead implantation, without jeopardizing the control of infection.

PMID- 19404803
TI  - Association between psoas abscess and prosthetic hip infection: a case-control
      study.
AB  - BACKGROUND AND PURPOSE: The relationship between prosthetic hip infection and a
      psoas abscess is poorly documented. We determined the frequency of prosthetic hip
      infections associated with psoas abscesses and identified their determinants.
      METHODS: We conducted a 2-year observational study. Data from patients with psoas
      abscesses that were associated with prosthetic hip infections were examined in a
      case-control study. RESULTS: Of 106 patients admitted to the Infectious Diseases
      Department with prosthetic hip infection, 13 also had a psoas abscess (12%; 95%
      CI: 6-19). By conditional logistic regression analysis, psoas abscesses were
      observed more frequently in cases of hematogenous prosthetic infections (OR = 93,
      p = 0.06) and in patients with a history of neoplasm (OR = 20, p = 0.03).
      INTERPRETATION: Our results suggest that the presence of psoas abscesses is a
      frequent but under-diagnosed complication of prosthetic hip infection. We
      recommend that an abdominal CT scan be performed on patients with hematogenous
      prosthetic hip infection or with a history of neoplasm.

PMID- 19404804
TI  - Poor results of drilling in early stages of juxta-articular osteonecrosis in 12
      joints affected by Gaucher disease.
AB  - BACKGROUND AND PURPOSE: Gaucher disease is heterogeneous. One of the most
      devastating complications is bone involvement, ranging from mild osteopenia to
      osteonecrosis, but no markers have been discovered to predict onset and/or
      progression. We describe our experience in a large referral center using drilling
      for juxta-articular osteonecrosis in young patients with Gaucher disease.
      PATIENTS AND METHODS: We retrospectively reviewed medical data from all patients
      who were recommended to undergo drilling for osteonecrosis of juxta-articular
      bone of the femoral head, the humeral head, or upper tibia for acute
      osteonecrosis at a pre-collapse stage. RESULTS: 11 patients (mean age 34 years)
      underwent drilling of 12 joints with juxta-articular osteonecrosis; 3 (mean age
      51 years) refused intervention. 9 joints that were drilled showed advancing joint
      degeneration within 0.5 to 4 years. 3 joints have undergone replacement. Of the 3
      joints that did not undergo drilling, 2 have undergone replacement and 1 has
      collapsed with osteoarthritis. INTERPRETATION: We found equally poor outcome with
      and without drilling. Effective intervention can only be achieved by improving
      our understanding of bone physiology and pathophysiology in Gaucher disease.

PMID- 19404805
TI  - Low rate of infected knee replacements in a nationwide series--is it an
      underestimate?
AB  - BACKGROUND AND PURPOSE: Specialist hospitals have reported an incidence of early
      deep infections of < 1% following primary knee replacement. The purpose of this
      study was to estimate the infection rate in a nationwide series using register
      based data. METHODS: The Finnish Arthroplasty Register (FAR) was searched for
      primary unicompartmental, total, and revision knee arthroplasties performed in
      1997 through 2003 and eventual revision arthroplasties. The FAR data on revision
      arthroplasties was supplemented by a search of the national Hospital Discharge
      Register (HDR) for debridements, partial and total revision knee replacements,
      resection arthroplasties, arthrodeses, and amputations. RESULTS: During the first
      postoperative year, 0.33% (95% CI: 0.13-0.84), 0.52% (0.45-0.60) and 1.91% (1.40
      2.61) of the primary UKAs, primary TKAs, and revision TKAs, respectively, were
      reoperated due to infection. The 1-year rate of reoperations due to infection
      remained constant in all arthroplasty groups over the observation period. The
      overall infection rate calculated using FAR data only was 0.77% (95% CI: 0.69
      0.86), which was lower, but was not, however, statistically significantly
      different from the overall infection rate calculated using endpoint data combined
      from FAR and HDR records (0.89%; 95% CI: 0.80-0.99). FAR registered revision
      arthroplasties and patellar resurfacing arthroplasties reliably but missed a
      considerable proportion of other reoperations. INTERPRETATION: More reoperations
      performed due to infection can be expected as the numbers of knee arthroplasties
      increase, since there has been no improvement in the early infection rate.
      Finnish Arthroplasty Register data appear to underestimate the incidence of
      reoperations performed due to infection.

PMID- 19404806
TI  - Reduced hospital stay, morphine consumption, and pain intensity with local
      infiltration analgesia after unicompartmental knee arthroplasty.
AB  - BACKGROUND AND PURPOSE: The degree of postoperative pain is usually moderate to
      severe following knee arthroplasty. We investigated the efficacy of local
      administration of analgesics into the operating area, both intraoperatively and
      postoperatively. METHODS: 40 patients undergoing unicompartmental knee
      arthroplasty (UKA) were randomized into 2 groups in a double-blind study
      (ClinicalTrials.gov identifier: NCT00653926). In group A (active), 200 mg
      ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 106 mL) were
      infiltrated intraoperatively into the soft tissue, while in group P (placebo), no
      injections were given. 21 hours postoperatively, 150 mg ropivacain, 30 mg
      ketorolac, and 0.1 mg epinephrine were injected intraarticularly via a catheter
      in group A, whereas patients in group P were injected with the same volume of
      saline (22 mL). RESULTS: Median hospital stay was shorter in group A than in
      group P: 1 (1-6) days as opposed to 3 (1-6) days (p < 0.001). Postoperative pain
      in group A was statistically significantly lower at rest after 6 h and 27 h and
      on movement after 6, 12, 22, and 27 h. Morphine consumption was statistically
      significantly lower in group A for the first 48 h, resulting in a lower frequency
      of nausea, pruritus, and sedation. Postoperatively, there were improved
      functional scores (Oxford knee score and EQ-5D) in both groups relative to the
      corresponding preoperative values. INTERPRETATION: Local injection of analgesics
      periarticularly at the end of the operation and intraarticularly at 21 h
      postoperatively provided excellent pain relief and earlier home discharge
      following UKA. There was a high degree of patient satisfaction in both groups
      after 6 months (Clinical Trials.gov: NCT 00653926).

PMID- 19404807
TI  - How to avoid complications of distraction osteogenesis for first
      brachymetatarsia.
AB  - BACKGROUND AND PURPOSE: Distraction osteogenesis may be used for the treatment of
      brachymetatarsia. However, few reports have been published on first metatarsal
      lengthening by this method. We evaluated the complications of distraction
      osteogenesis for first brachymetatarsia and here we provide a solution. PATIENTS
      AND METHODS: 16 patients (27 feet) underwent distraction osteogenesis for first
      brachymetatarsia. Mean age at time of surgery was 20 (12-34) years and mean
      duration of postoperative follow-up was 5 (2-13) years. A unilateral external
      fixator was fixed at the medial aspect of the metatarsus. The distraction axis
      was parallel to the plantar surface of the foot in the sagittal plane and to the
      second metatarsal axis in the transversal plane. RESULTS: First metatarsal length
      expressed as a proportion of second metatarsal length was 60% (55-64). Average
      degree of metatarsal lengthening was 42% (34-54), and the average lengthening
      index was 64 (39-93) days/cm. The most common complication was stiffness of the
      metatarsophalangeal joint (12 feet). Deformities that included cavus foot and
      hallux valgus occurred in 3 feet each, and callus fractures occurred in 3 feet.
      The other complications were pin breakage and pin tract infection in 2 feet each.
      INTERPRETATION: Distraction osteogenesis for first brachymetatarsia can give
      satisfactory cosmetic and functional results. However, several complications are
      commonly encountered. This report on complications and their solutions may help
      those attempting distraction osteogenesis for first brachymetatarsia.

PMID- 19404808
TI  - No evidence for the effectiveness of bracing in patients with thoracolumbar
      fractures.
AB  - BACKGROUND AND PURPOSE: The use of braces is widespread in patients with
      thoracolumbar fractures. The effectiveness of bracing, however, is controversial.
      We sought evidence for the effect of bracing in patients with traumatic
      thoracolumbar fractures based on outcome and length of hospital stay (LOS).
      Furthermore, we evaluated the incidence of complications of bracing. METHODS: An
      electronic search strategy with extensive MeSH headings was used in various
      databases to identify studies that compared bracing and non-bracing therapies.
      Two reviewers independently selected systematic reviews, randomized controlled
      trials (RCTs), controlled clinical trials, and observational studies, and both
      assessed the methodological quality and extracted the data. RESULTS: No
      systematic reviews or RCTs were found. 7 retrospective studies were included.
      None of these studies showed an effect of bracing. Because of poor methodological
      quality, no best-evidence synthesis could be performed. One observational study
      was selected in which a complication of bracing was reported. INTERPRETATION: In
      the present literature, there is no evidence for the effectiveness of bracing in
      patients with traumatic thoracolumbar fractures. The lack of high-quality studies
      prevents relevant conclusions from being drawn.

PMID- 19404809
TI  - The Western Ontario Shoulder Instability Index (WOSI): validity, reliability, and
      responsiveness retested with a Swedish translation.
AB  - BACKGROUND AND PURPOSE: The WOSI score questionnaire is a tool designed for self
      assessment of shoulder function for patients with instability problems. We made a
      translation into Swedish and retested the score by analyzing the psychometric
      properties validity, reliability, and responsiveness. PATIENTS AND METHODS: 3
      patient materials were used for the assessment: (A) a follow-up on a group of 32
      patients more than 8 years after having primary posttraumatic shoulder
      dislocation. Evaluation of Pearson's correlation coefficient between WOSI and
      Rowe score and for test-retest reliability was made; (B) 22 patients, treated
      with a surgical stabilization of the shoulder at our department, were evaluated
      with Pearson's correlation coefficient between WOSI and EQ-5D, and between WOSI
      and a VAS-scale of general shoulder function. Also, Cronbach's alpha, effect
      size, and floor, and ceiling effects were analyzed; (C) 45 students with healthy
      shoulders (reference group) had their WOSI score determined. RESULTS: The
      construct validity (Pearson's correlation coefficient) was adequate (0.59)
      between the WOSI score and the Rowe score. The agreement with an ICC value (test
      retest) for the WOSI score was excellent (0.94). Cronbach's alpha (internal
      consistency) was satisfactory, with 0.89 preoperatively and 0.95 postoperatively.
      All 22 patients in group B reported improvement in the WOSI score (mean 29%).
      Responsiveness was excellent, with an effect size of 1.67 for the WOSI score.
      There were no floor or ceiling effects for the Swedish WOSI score. The mean WOSI
      score from group C with 45 normal healthy shoulders was 96%, with no floor but
      high ceiling effects. INTERPRETATION: WOSI score does not require an examination
      of the patient and can be administered by mail. The high ICC and sensitivity
      makes it able to monitor an individual patient's progress. At this retest, the
      WOSI score has good validity, a high degree of reliability, and a high degree of
      responsiveness, all at the same level as in the original publication. We
      recommend the WOSI when evaluating patients with instability problems.

PMID- 19404810
TI  - Different osteosyntheses for Colles' fracture: a mechanical study in 42 cadaver
      bones.
AB  - BACKGROUND AND PURPOSE: In recent years several different plate designs for
      internal fixation of fractures of the distal radius have been developed. However,
      few biomechanical studies have been performed to compare these new implants. The
      purpose of this study was to compare the mechanical properties of 5 different
      commercially available plates (3 volar and 2 dorsal) with standard K-wire
      fixation using a distal radial cadaver model. MATERIAL AND METHODS: 42 human
      radial bones from 26 cadavers were included. The bone mineral density (BMD) was
      measured by DEXA in all bones, and the radial bones were assigned to 6 equiv
      alent groups based on bone density and total amount of mineral. A distal radial
      osteotomy was done and a dorsal 30-degree wedge of bone was removed. 1 K-wire
      fixation group and 5 plate groups were tested for rigidity, yield load, and
      maximum load. RESULTS: When data from dorsally and volarly applied plates were
      pooled, we did not find any statistically significant differences between them
      regarding stiffness, yield load, and maximum load. The K-wire group showed
      significantly lower yield load than 3 of the plate groups. There were no
      statistically significant differences in yield load between the 5 plate groups.
      The K-wire group showed lower rigidity than the plate groups. The K-wire group
      and 1 plate group failed at a statistically significant lower maximum load than
      the 4 other plate groups. INTERPRETATION: The volar plates had the same
      mechanical stability as the dorsally applied plates, and they are therefore a
      good alternative to dorsally applied plates. K-wire osteosynthesis was inferior
      to plate osteosyntheses regarding all mechanical properties.

PMID- 19404813
TI  - Revision arthrodesis of the ankle: posterior inlay bone grafting in 11 patients.

PMID- 19404811
TI  - Sonication is superior to scraping for retrieval of bacteria in biofilm on
      titanium and steel surfaces in vitro.
AB  - BACKGROUND AND PURPOSE: Low-virulence implant infections are characterized by
      bacterial colonization of the implant with subsequent biofilm formation. In these
      cases, soft tissue biopsies often prove to be culture negative. Consequently,
      detachment of the causative adherent bacteria is crucial for correct
      microbiological diagnosis. Using an in vitro model, we compared 4 methods of
      biofilm sampling from metal surfaces. METHODS: Discs of titanium and steel were
      incubated in the presence of Staphylococcus aureus, Staphylococcus epidermidis,
      Enterococcus faecalis, and Propionibacterium acnes in Mueller Hinton broth. Non
      adherent bacteria were removed by repeated rinsing of the discs. 10 parallels of
      each disc were subjected to 1 of 4 methods for bacterial recovery: (A) sonication
      of the discs, (B) scraping of the discs using surgical blades followed by
      streaking of the blades onto agar plates, (C) scraping of the discs followed by
      vortex mixing of the surgical blades, and (D) scraping of the discs followed by
      sonication of the surgical blades. Quantitative bacterial cultures were performed
      for each sampling method. RESULTS: With the exception of S. epidermidis on steel,
      sonication efficiently and reliably dislodged biofilm bacteria. The scraping
      methods employed did not detach bacteria embedded in biofilm. INTERPRETATION:
      Scraping of metal surfaces is not an adequate method for sampling of biofilm
      bacteria in vitro.

PMID- 19404812
TI  - Tourniquets and exsanguinators: a potential source of infection in the orthopedic
      operating theater?
AB  - BACKGROUND AND PURPOSE: Fomites are increasingly being recognised as a source of
      hospital-acquired infection. We have therefore assessed tourniquets and
      exsanguinators for the presence of bacterial pathogens in 1 elective and 2 trauma
      orthopedic hospitals. MATERIAL AND METHODS: Swabs were taken prior to and after
      decontaminating these devices with 1 of 3 different cleaning modalities. These
      were then assessed for colony counts and organisms identified. RESULTS: Bacteria
      commonly implicated in surgical site infections such as coagulase-negative
      staphylococci, Staphylococcus aureus and Proteus spp. were prevalent. We also
      found a resistant strain of Acinetobacter and Candida. Exsanguinators were the
      most heavily contaminated devices, and colony counts in the trauma hospitals were
      up to 400% higher than in the elective hospital. Alcohol- and non-alcohol-based
      sterile wipes were both highly effective in decontaminating the devices.
      INTERPRETATION: Infectious organisms reside on the tourniquets and exsanguinators
      presently used in the orthopedic theater. These fomites may possibly be a source
      of surgical site infection. We have demonstrated a simple and effective means of
      decontaminating these devices between cases.

PMID- 19404815
TI  - Reflections on 40 years of involvement in 'community and politics' in psychiatry.

PMID- 19404816
TI  - Reflections on facilitated discharge from a mental health service.
AB  - OBJECTIVE: The aim of this paper is to review research evidence and describe our
      experience of facilitated discharge from mental health services to primary care.
      METHOD: A literature review of facilitated discharge was conducted. In addition,
      the clinical characteristics of 21 discharged and 21 non-discharged patients from
      one shared care service were compared in a retrospective file review. Thirty-one
      patients in another facilitated discharge program were surveyed. RESULTS:
      Discharged patients had a higher level of function. There was a trend towards
      discharged patients being female and employed with less chronic illness,
      involuntary treatment, behavioural symptoms, depot medication, triage contact,
      service contact with family, and more mood disorder. Of the 10 survey
      respondents, 60% reported feeling better compared with their last service
      contact, 70% felt not having contact was a good thing and most saw their doctors
      regularly and reported a good relationship. CONCLUSIONS: There was a trend
      towards more stable patients being discharged and it appeared that they responded
      positively to this, without a clear indication of which factors best determine
      suitability for discharge. Consequently, we elected to incorporate discharge
      planning processes as a core function of case management and increase shared care
      with the primary care sector.

PMID- 19404817
TI  - The impact of a changed environment on arousal levels of patients in a secure
      extended rehabilitation facility.
AB  - OBJECTIVE: This study sought to investigate the effect of changes of the physical
      ward environment on levels of arousal and aggression in long-stay patients in a
      secure extended rehabilitation facility. METHOD: Seclusion episodes, extended
      seclusion episodes, staff report of aggressive incidents and Brief Psychiatric
      Rating Scale (BPRS) measures of psychopathology were compared in the same group
      of long-stay rehabilitation patients over a period of 3 months before and 3
      months after a move from a temporary, refurbished medical ward to a large, light
      filled, purpose-built facility. RESULTS: Fifteen patients were present during
      both investigation periods. The majority were male (80%) and had a diagnosis of
      schizophrenia (53%) or schizoaffective disorder (13%). There were statistically
      significant reductions in the mean number of seclusion episodes, mean number of
      extended seclusion episodes (> 4 hours) and BPRS total score following the move.
      There were statistically significant increases in ambient light conditions in the
      new unit. CONCLUSIONS: The physical environment of long-stay rehabilitation wards
      may influence aggressive behaviour and arousal in chronically ill patients.

PMID- 19404818
TI  - Improvised explosive devices and traumatic brain injury: the military experience
      in Iraq and Afghanistan.
AB  - OBJECTIVE: The current conflicts in Iraq and Afghanistan have seen frequent use
      of improvised explosive devices resulting in thousands of casualties, with
      traumatic brain injuries particularly common. The recent literature is reviewed
      to provide information to clinicians on the management of this condition. METHOD:
      A Medline search from 2001-2008, using the terms Afghanistan, blast injury,
      improvised explosive devices, Iraq and traumatic brain injury, was performed.
      RESULTS: The United States military experience predominates in the literature.
      The use of body armour and other advances has led to improved survival rates
      among blast injury victims. Resultant neuropsychiatric injuries, in particular
      traumatic brain injuries, are discussed. There is debate about the prevalence of
      traumatic brain injuries. The diagnosis, management, relationship with
      posttraumatic stress disorder and prognosis of traumatic brain injury are
      reviewed. CONCLUSIONS: Traumatic brain injury has been described as the
      'signature wound' of the current conflicts in Iraq and Afghanistan. While this
      term is highly debatable and probably unhelpful, clinicians need to know about
      this condition to provide the best management.

PMID- 19404819
TI  - A brief, descriptive typology of depressed mood.
AB  - OBJECTIVE: The purpose of this paper is to consider the potential clinical
      utility of a descriptive typology of negative mood states that can present as,
      and tend to get loosely subsumed under, the broad ranging term, 'depression'.
      METHOD: Information and ideas from clinical practice and the existing literature
      have been brought together with a view to compiling a provisional, brief,
      descriptive typology of depressed mood. CONCLUSION: A qualitative typology of
      various kinds of depressed mood has heuristic value in engaging, formulating and
      planning treatment for people presenting with 'depression'.

PMID- 19404820
TI  - Merleau-Ponty and me: some phenomenological reflections upon my recent bone
      marrow transplant.
AB  - OBJECTIVE: During my illness and transplant I experienced an overwhelming
      existential crisis involving a complex intertwining of meaning and body which was
      often ignored, rejected, or misunderstood by others and at times by myself, which
      led to painful feelings of alienation. My treatment and my own conceptualizations
      seemed founded on assumptions of a separation of body and mind that were not true
      to what I was experiencing. I searched for a more accurate understanding, which I
      eventually found in the writings of the French existential philosopher Merleau
      Ponty. CONCLUSIONS: Merleau-Ponty's extensive elaboration of the deep ambiguity
      of our existence as body-subjects provides an alternative model to those of the
      mind/body dichotomy currently in vogue in medicine and psychiatry. I found his
      writings a useful framework within which to comprehend my experiences. I wanted
      to write about these experiences and how they relate to Merleau-Ponty's insights
      because I found that those individuals who were able to relate to me at this
      level of existential ambiguity were invaluable to my recovery.

PMID- 19404824
TI  - The doctrine of integration in psychiatry and the pre-Socratics.

PMID- 19404821
TI  - Hallucinations arising in the context of torn attachment, traumatic childhood and
      tapeworms.
AB  - OBJECTIVE: The aim of this paper is to describe the processes underlying
      psychotic symptoms in an adolescent who presented to our service at the age of 15
      years. CONCLUSION: A teenage female presented having experienced her early
      childhood in a war-torn third-world country, during which time her mother died,
      and she suffered worm infestation, neglect and trauma, before being adopted by a
      family in a developed country, where she lived for several years prior to
      relocating to Australia. The presenting complaints included longstanding anxiety,
      depressive and dissociative symptoms, with subsequent behavioural problems and
      learning difficulties. More recently, she had developed auditory hallucinations,
      and the antipsychotic she had been taking was beneficial. An MRI of the brain
      demonstrated lesions in keeping with healed parasitic disease
      (neurocysticercosis). The patient's hallucinations are discussed in the context
      of the relationship between a traumatic childhood and psychosis, and
      neurocysticercosis. Within months of her presentation, the hallucinations
      resolved as her step-mother became more available. Her antipsychotic medication
      is being carefully decreased, and the patient is engaging in psychological
      therapies to deal with her past trauma and disrupted attachment.

PMID- 19404831
TI  - Parental locus of control and psychological well-being in mothers of children
      with intellectual disability.
AB  - BACKGROUND: Psychological mechanisms may help to explain the variance observed in
      parental psychological adjustment in parents of children with intellectual
      disability (ID). In this study, parental locus of control and its role in
      relation to maternal psychological well-being was explored. METHOD:
      Questionnaires were sent to 91 mothers of children with ID at two time points, 18
      months apart. RESULTS: Parental locus of control was associated with both
      maternal positive perceptions and with maternal distress. Regression analyses
      showed that dimensions of parental locus of control were significant predictors
      of negative maternal adjustment. Maternal positive perceptions were predicted by
      perceived control of the child and belief in fate or chance. Overall parental
      internal-external locus of control entered into a bidirectional relationship with
      stress over 18 months. CONCLUSIONS: Parental locus of control is a construct that
      may explain some of the variance in maternal well-being and thus is a construct
      that merits further research.

PMID- 19404832
TI  - Assessing anger in people with intellectual disability.
AB  - BACKGROUND: There is a growing interest in the use of cognitive approaches for
      the treatment of psychological difficulties with people who have intellectual
      disability. The aim of the present study was to investigate the properties of an
      anger inventory, the relationship between self-reported and staff-reported levels
      of anger, and the relationship between different staff measures. METHOD: Two
      studies are described that use self-report and staff-report measures. The first
      study employs a cross sectional design and the second, a longitudinal design.
      RESULTS: No relationship was found between self-reported and staff-reported
      levels of anger on the first measurement occasion, but on the second measurement
      occasion after some intervention a significant relationship was found. If staff
      had accompanied individuals during an intervention a larger correlation was
      found. CONCLUSION: These results suggest that staff may require specific training
      or exposure to a therapeutic environment before they can predict the response of
      people with intellectual disability on the anger inventory. This suggests that
      involvement of care staff in interventions may be useful therapeutically.

PMID- 19404829
TI  - Adapting mass spectrometry-based platforms for clinical proteomics applications:
      The capillary electrophoresis coupled mass spectrometry paradigm.
AB  - Single biomarker detection is common in clinical laboratories due to the
      currently available method spectrum. For various diseases, however, no specific
      single biomarker could be identified. A strategy to overcome this diagnostic void
      is to shift from single analyte detection to multiplexed biomarker profiling.
      Mass spectrometric methods were employed for biomarker discovery in body fluids.
      The enormous complexity of biofluidic proteome compartments implies upstream
      fractionation. For this reason, mass spectrometry (MS) was coupled to two
      dimensional gel electrophoresis, liquid chromatography, surface-enhanced laser
      desorption/ionization, or capillary electrophoresis (CE). Differences in
      performance and operating characteristics make them differentially suited for
      routine laboratory applications. Progress in the field of clinical proteomics
      relies not only on the use of an adequate technological platform, but also on a
      fast and efficient proteomic workflow including standardized sample preparation,
      proteomic data processing, statistical validation of biomarker selection, and
      sample classification. Based on CE-MS analysis, we describe how proteomic
      technology can be implemented in a clinical laboratory environment. In the last
      part of this review, we give an overview of CE-MS-based clinical studies and
      present information on identity and biological significance of the identified
      peptide biomarkers providing evidence of disease-induced changes in proteolytic
      processing and posttranslational modification.

PMID- 19404833
TI  - Effects of child characteristics on the outcomes of a parent support program.
AB  - BACKGROUND: Previous research has reported on the effectiveness of the Signposts
      program for supporting families of children with an intellectual disability and
      difficult behaviour (Hudson et al., 2003; Hudson, Cameron, & Matthews, 2008).
      This paper reports on an investigation of the extent to which child
      characteristics moderate the effectiveness of the program. METHOD: Data collected
      from 689 participants in the Signposts program were analysed to examine if the
      child characteristics of gender, age, or associated disability impacted on
      outcomes. RESULTS: The gender analyses produced mean effect sizes of 0.39 for
      boys and 0.42 for girls; however, this difference was not statistically
      significant. The age analyses produced mean effect sizes of 0.38 for children
      aged 2-5 years, 0.42 for children aged 6-12 years, and 0.30 for children aged 13
      18 years; however, these differences among the age groups were not statistically
      significant. The associated disability analyses across 7 groups produced mean
      effect sizes ranging from 0.31 to 0.75; however, the differences among these
      groups were not statistically significant. CONCLUSIONS: First, gender was not a
      moderating variable. Second, while the effect size for the older age group seemed
      to be marginally lower than that of the other two groups, age was not found to be
      a moderating variable. Finally, type of associated disability was not found to be
      a moderating variable. Methodological limitations of the study necessitate care
      in interpreting the findings.

PMID- 19404834
TI  - Enrichment, stress, and growth from parenting an individual with an autism
      spectrum disorder.
AB  - BACKGROUND: Past researchers have focused primarily on the associated negative
      impact of caring for a child with special needs. In this study, caregivers report
      the enrichment and stress of caring for a child with an autism spectrum disorder.
      METHOD: Eighty caregivers completed the Social Communication Questionnaire (SCQ),
      Effects of the Situation Questionnaire (ESQ), and Posttraumatic Growth Inventory
      (PTGI). Enrichment and stress scores were compared to symptom severity data and
      posttraumatic growth scores. RESULTS: Consistent with prior research, caregivers
      reported greater levels of stress than enrichment. On just over half of the
      stress/enrichment variables, parental ratings of stress and enrichment were
      negatively correlated. Scores of total stress and enrichment were not correlated
      to the severity of the individual's symptoms or caregivers' growth scores.
      CONCLUSIONS: These findings suggest that although stress is a major concern for
      caregivers, enrichment and growth may also occur in varying degrees.

PMID- 19404835
TI  - Searching for acceptance: challenges encountered while raising a child with
      autism.
AB  - BACKGROUND: Autism, a severe childhood disorder, affects the family system in
      dramatic ways. METHOD: Fifty-two parents of children with autism were interviewed
      to explore their struggles and their successes qualitatively. RESULTS: Five
      challenges that emerged from these family's experiences were: Development,
      Questioning, Devastation, Solutions, and Growth. Every parent described the
      confusion that resulted from their child's behavioural presentation and the
      feelings of loss and devastation that occurred after discovering their child has
      autism. Parents, however, were swift and eager to mobilise resources to help
      their child, sometimes in any possible way. Almost every parent described
      significant, positive experiences that resulted from raising a child with autism,
      despite the hardships. CONCLUSIONS: The findings of this study provide important
      considerations for professionals and families.

PMID- 19404836
TI  - The impact of child, family, and professional support characteristics on the
      quality of life in families of young children with disabilities.
AB  - BACKGROUND: Families of young children with disabilities are faced with ongoing
      challenges that impact various aspects of family life. Given the increasing
      emphasis on promoting positive outcomes in these families, the overall aim of the
      current study was to examine the contribution of child, family, and support
      characteristics to the quality of life in families of young children with
      disabilities. METHOD: The sample was recruited from several early childhood
      intervention programs within metropolitan Melbourne, Australia, and consisted of
      64 families of children aged between 3 and 5 years with a developmental delay or
      disability. RESULTS: As a whole, parental perceptions and experiences of family
      centred professional support was one of the strongest predictors of family
      quality of life. The perceived intensity of child behavioural problems as well as
      support from extended family members also accounted for a significant proportion
      of unique variance in predicting quality of family life. CONCLUSION: The current
      findings provide further evidence for the importance of a family-focused approach
      to intervention that acknowledges and provides support that is tailored to the
      unique needs of each individual family. The practical implications of these
      results as well as directions for future research are discussed.

PMID- 19404837
TI  - Secondary special educators' transition involvement.
AB  - BACKGROUND: Different roles and responsibilities are required of school
      professionals to facilitate students' successful transition from school to post
      school lives. Special educators' involvement in transition services is essential
      for better post-school outcomes for students with disability. METHOD: The
      Transition Involvement Survey with five domains was developed for the study and a
      total of 343 secondary special educators in the United States participated.
      MANOVA and post hoc discriminant analysis were used to examine group differences
      across the five domains. RESULTS: Special educators rated highly in their
      involvement in transition planning but less so in other domains. Receiving in
      service training was significantly related to educators' transition involvement
      but receiving pre-service training was found to be only partly related.
      CONCLUSION: The gap between special educators' knowledge and involvement in
      extending transition services affects the provision of services. Recommendations
      from this study support stronger personnel preparation to improve this situation.

PMID- 19404838
TI  - Peer-mediated teaching and augmentative and alternative communication for
      preschool-aged children with autism.
AB  - BACKGROUND: The aim of this study was to assess the effectiveness of two
      communication interventions for preschool-aged children with autism. METHOD: Six
      typically developing peers were taught to implement peer-mediated naturalistic
      teaching, with and without a speech generating device (SGD), during play sessions
      with 3 classmates with autism in three preschools. Generalisation probes were
      conducted during mealtimes at the preschools. A multiple baseline design was used
      to assess the outcomes of the two intervention conditions. RESULTS: All 3
      children with autism increased their communicative behaviours immediately
      following the introduction of the two interventions, and generalised these
      increases to mealtime interactions with their peers. However, only 1 child
      maintained these increases in communication. CONCLUSION: These results provide
      preliminary evidence for the effectiveness of combining peer-mediated
      naturalistic teaching with the use of SGDs for preschool-aged children with
      autism. Suggestions for improving the maintenance of intervention effects are
      provided.

PMID- 19404839
TI  - My shield will protect me against the ANTS: treatment of PTSD in a client with an
      intellectual disability.
AB  - BACKGROUND: There are limited interventions for individuals with posttraumatic
      stress disorder (PTSD) who also have an intellectual disability. This paper
      reports the successful treatment of a client with an intellectual disability who
      experienced PTSD following abuse in an intimate relationship. We describe the use
      of an innovative coping technique ("the shield") developed by the first author to
      allow exposure to intrusive traumatic memories. METHOD: Treatment involved
      exposure, stress reduction techniques, and modified cognitive techniques.
      RESULTS: After 9 sessions of therapy over 3 months, the client had experienced no
      flashbacks. These gains were maintained at a 5-month follow-up. CONCLUSION: PTSD
      symptoms were successfully treated and the client reported additional
      improvements in overall functioning. Limitations and questions about the
      mechanism of action are raised.

PMID- 19404840
TI  - None of the As in ABA stand for autism: dispelling the myths.

PMID- 19404842
TI  - Splenic irradiation in the management of Waldenstrom macroglobulinemia.

PMID- 19404843
TI  - A practical approach to the understanding and diagnosis of lymphoma: an
      assessment of the WHO classification based on immunoarchitecture and immuno
      ontogenic principles.
AB  - This review aims to interrelate the major lymphoma types in the current World
      Health Organization (WHO) classification to construct a framework for
      understanding and diagnostic application. Multiple morphological, phenotypical
      and molecular genotypical data are assessed in order to categorise lymphomas into
      germinal centre (GC) and extracentric (EC) subgroups. GC entities [lymphocyte
      predominant Hodgkin, follicular, Burkitt's, angioimmunoblastic T-cell and diffuse
      large B-cell lymphoma (DLBCL) with GC profile] express bcl-6, CD10 and/or the GC
      homing chemokine CXCL13, and harbour ongoing somatic hypermutations (SHM), but
      not Epstein-Barr virus (EBV) in its higher latency states. Post-GC entities
      [classical Hodgkin, marginal zone and lymphoplasmacytic lymphomas, half of
      chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), DLBCL with
      'activated' or post-GC profile, primary effusion lymphoma, plasmacytoma and
      myeloma] express, instead, MUM.1 and/or CD138, harbour static rather than ongoing
      SHM, and may harbour EBV in higher latency states. The remainder of CLL/SLL and
      the majority of mantle cell lymphoma without SHM constitute the pre-GC ('naive')
      category, with coexpression of IgD and CD5. Lymphomas can be categorised across
      lineage (B- or T-cell) and relationship against host immune response (Hodgkin or
      non-Hodgkin) into GC and EC groups, affording leverage in their differential
      diagnosis.

PMID- 19404844
TI  - Activation of extracellular regulated kinases (ERK1/2) predicts poor prognosis in
      urothelial bladder carcinoma and is not associated with B-Raf gene mutations.
AB  - AIM: The analysis of the presence of B-Raf gene mutations in relation to ERK1/2
      activation in bladder urothelial carcinoma (UC), in order to determine their
      potential role in tumour aggressiveness and patients' survival. METHODS:
      Polymerase chain reaction-single strand confirmation polymorphism (PCR-SSCP) and
      sequencing analysis were used for B-Raf gene mutation detection. pERK1/2 and
      FGFR3 expression were examined by immunohistochemistry in 152 and 116 primary
      UCs, respectively. RESULTS: None of the cases displayed mutations in exon 15 of B
      Raf gene. Nuclear or cytoplasmic pERK immunoreactivity was displayed in 99.3% and
      96.7% of cases, respectively. pERK nuclear expression increased with histological
      grade and with T-category. Nuclear and cytoplasmic pERK expression was unrelated
      to FGFR3 expression. In univariate survival analysis of muscle-invasive
      carcinomas, advanced T-category and higher pERK nuclear expression (p = 0.018)
      adversely affected survival. However, multivariate analysis in non-invasive as
      well as in muscle-invasive carcinomas selected only T-category as a significant
      prognosticator. CONCLUSIONS: Our findings suggest that elevated pERK expression
      occurs in UCs in the absence of B-Raf mutations and is not correlated with FGFR3
      over-expression. Moreover, it implicates ERK activation in the acquisition of a
      more aggressive phenotype. However, the assessment of pERK1/2 expression does not
      seem to add to the prognostic information provided by classical prognosticators.

PMID- 19404845
TI  - Expression and clinical significance of Notch receptors in human renal cell
      carcinoma.
AB  - AIMS: The pathological roles of Notch receptors in renal cell carcinoma (RCC) are
      still unclear, although Notch receptors have been shown to have an effect on many
      malignant tumours. Therefore, in this study, we examined the patterns of
      expression and clinical significance of Notch receptors in RCC. METHODS: Eighty
      four cases of renal cell carcinoma tissues were detected by immunohistochemistry.
      Eleven paired fresh surgical renal cell carcinoma and adjacent non-neoplastic
      renal samples were analysed by Western blot and reverse transcriptase polymerase
      chain reaction. In addition, the expression of Notch receptors in renal cancer
      cell lines (A498 and 786-O) and human normal kidney tubule epithelial cell lines
      (HK-2 and HKC) were analysed by Western blot. RESULTS: The expression levels of
      Notch1 and Notch4 were absent or significantly decreased in renal cell carcinoma
      tissues compared with the adjacent non-neoplastic tissues [Notch1: 22.6% (19/84)
      versus 78.7% (59/75); Notch4: 27.4% (23/84) versus 73.3% (55/75); p < 0.05).
      Moreover, the levels of expression of Notch1 and Notch4 were also markedly down
      regulated in human renal cancer cell lines. Notch1 was negatively correlated with
      tumour stage, while Notch4 expression had no significant association with
      pathological parameters. The levels of expression of Notch2 and Notch3 were
      minimally detected in tumours and non-neoplastic tissues. CONCLUSION: Our
      findings indicated that the expression of Notch receptors was deregulated and
      Notch signalling might play an important role in the progress of renal cell
      carcinoma.

PMID- 19404846
TI  - Glomerular basement membrane thickness in an Asian population using a novel image
      analysis software.
AB  - AIMS: We aimed to develop an image analysis software that enabled measurement of
      glomerular basement membrane (GBM) thickness. METHODS: With this software, we
      evaluated the range of GBM widths found in a cohort of Asian patients diagnosed
      with a spectrum of renal diseases including minimal change/IgM nephropathy, focal
      and segmental glomerulosclerosis, IgA nephropathy, systemic lupus erythematosus
      nephritis, diabetic nephropathy, pauci-immune crescentic glomerulonephritis, thin
      basement membrane disease, and tubulointerstitial nephritis. Measurements were
      taken from a minimum of five glomerular capillary loops of each glomerulus. For
      each loop, at least 10 different points of the GBM were measured. RESULTS: The
      average GBM width measured for minimal change disease was 347.4 +/- 9.0 nm, with
      the highest value being 403.9 nm and lowest being 214.7 nm. No association was
      found between GBM width and gender. We found a significant increase in GBM width
      in pathological states like lupus nephropathy (p < 0.0001), diabetic nephritis (p
      < 0.001) and tubulointerstitial nephritis (p < 0.01) as compared with minimal
      change disease. Only one case of thin membrane nephropathy (198.7 nm) was
      available for analysis and we found a significant thinning of the GBM.
      CONCLUSIONS: These observations provide insights into the range of GBM thickness
      in several disease states and support the use of this novel software in the daily
      diagnostic laboratory setting.

PMID- 19404847
TI  - Use of X-chromosome inactivation pattern and laser microdissection to determine
      the clonal origin of focal nodular hyperplasia of the liver.
AB  - AIM: To determine the clonal origin of the whole lesion and each nodule of focal
      nodular hyperplasia (FNH) and elucidate its nature, simultaneously comparing the
      clonal composition with hepatocellular adenoma (HA). METHODS: Nine FNHs from
      eight women, two HAs and four hepatocellular carcinomas (HCCs) were examined by
      clonality assays based on X-chromosomal inactivation mosaicism in females and
      laser microdissection. Genomic DNA was isolated from each nodule, the whole
      lesion and surrounding liver parenchyma, pretreated with Hpa II or Hha I, and
      amplified via nested PCR for phosphoglycerate kinase (PGK) and androgen receptor
      (AR) genes. The single nucleotide polymorphism at the PGK locus was identified by
      incubation with Bst XI and agarose gel electrophoresis, and the CAG repeat length
      polymorphism at AR locus was revealed on denaturing polyacrylamide gels and
      visualised by silver staining. RESULTS: Monoclonality was confirmed in both of
      the two HAs and all of the four HCCs examined, while polyclonality was shown in
      all nine FNHs as determined by the whole lesions, demonstrating their distinction
      from neoplastic lesions. A total of 108 nodules, including 96 nodules of altered
      hepatocytes (NAH) and 12 ordinary regenerative nodules (ORN), were microdissected
      from eight of the nine FNH lesions. Loss of X-chromosomal inactivation mosaicism
      was demonstrated in 39 (40.6%) of 96 NAHs, indicating the monoclonal, neoplastic
      nature. In contrast, polyclonality was demonstrated in all of the 12 ORNs and the
      surrounding liver parenchyma. CONCLUSIONS: FNH is composed of numerous NAHs and
      ORNs. The whole lesion shows a polyclonal cell composition, but neoplastic
      transformation has occurred in some of the nodules. Clonal assay is useful for
      its distinction from HA, and sampling the whole or larger part of the lesion is
      necessary.

PMID- 19404848
TI  - Immunohistochemical expression of EGFR in colorectal carcinoma correlates with
      high but not low level gene amplification, as demonstrated by CISH.
AB  - AIM: To assess and compare immunohistochemical expression of epidermal growth
      factor receptor (EGFR) with gene amplification as demonstrated by chromogenic in
      situ hybridisation (CISH), in colorectal adenocarcinoma. METHODS: Sections from
      100 consecutive colorectal cancer resection specimens were stained for EGFR using
      immunohistochemistry and CISH. Immunohistochemical assessment was independently
      performed at two laboratories, using the same antibody and protocols. RESULTS:
      With immunohistochemistry, strong circumferential membrane staining (3+ staining)
      was demonstrated in only 5% of cases, and this was only focal in three of five
      cases. At one laboratory, weak or incomplete staining (1+ or 2+) was observed in
      five further cases (5%), which had been negative at the other laboratory. CISH
      demonstrated high level gene amplification (>10 copies/nucleus) in the same five
      cases which had demonstrated 3+ staining with immunohistochemistry, and in those
      cases where the staining was focal, the amplification was demonstrated in the
      same foci of the tumour. Five further cases (5%) had low level amplification (5
      10 copies per nucleus); these cases did not exhibit significant positive staining
      with immunohistochemistry. All the cases which demonstrated gene amplification
      (high or low level) arose in the distal colon. There was no correlation between
      gene amplification status and a variety of other variables, including stage at
      diagnosis, mucinous differentiation, neuroendocrine differentiation, or loss of
      expression of mismatch repair proteins. CONCLUSIONS: Immunohistochemical
      expression of EGFR is variable between laboratories, even using standardised
      protocols. 3+ staining is predictive of high level gene amplification, but
      correlates very poorly with low level amplification, which may still be
      clinically significant. In some cases gene amplification was only focal, offering
      a potential explanation for poor response to targeted therapy in patients with
      EGFR positive tumours.

PMID- 19404849
TI  - Histopathology reporting of breast cancer in Queensland: the impact on the
      quality of reporting as a result of the introduction of recommendations.
AB  - AIMS: Recommendations for the pathology reporting of breast cancer were released
      in Australia to ensure detailed communication of important prognostic features
      and good patient management. An audit of the reporting of invasive breast cancer
      in Queensland was conducted to determine how well these guidelines were utilised
      in 2004. METHODS: A random sample of reports was audited for inclusion of
      recommended criteria. The proportion of reports meeting each of the criteria was
      determined and compared across whether the report was in a synoptic report
      template or in a free text format. Comparison was made with published data from
      prior to the release of the recommendations. RESULTS: Of the 419 reports in the
      sample, at least 90% of reports included lesion size, histological type,
      histological grade, lymph node involvement, margins of excision, lymphovascular
      invasion, and changes in adjacent breast tissue individually, and 74% included
      all seven of these essential criteria. Synoptic reports accounted for 76% of the
      sample and were significantly more likely to have documented grade (p < 0.001),
      quadrant (p = 0.003), calcification (p < 0.001), lymphovascular invasion (p <
      0.001), changes in non-neoplastic breast (p < 0.001) and ductal carcinoma in situ
      criteria (p < 0.001) compared with free text report format. The most notable
      improvements since the implementation of the recommendations were in
      documentation of adjacent breast tissue (92% versus 49%) and lymphovascular
      invasion (97% versus 54%). CONCLUSION: Breast cancer reporting in Queensland has
      improved since the implementation of the recommendations, however further
      improvements would likely be seen if there is more widespread utilisation of a
      synoptic report format.

PMID- 19404850
TI  - Expression and prognostic significance of SIRT1 in ovarian epithelial tumours.
AB  - AIMS: Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent
      deacetylase. Recently, some studies have suggested that SIRT1 could be over
      expressed in breast, prostate and colon cancers and up-regulated SIRT1
      inactivates p53 by deacetylation. Therefore, we investigated the prevalence and
      the prognostic impact of SIRT1 and p53 expression in ovarian epithelial tumours.
      METHODS: Immunohistochemical expression of SIRT1 and p53 were evaluated using
      tissue microarray in 40 cases of benign epithelial tumours, 36 cases of
      borderline tumours, and 90 cases of malignant tumours. RESULTS: Expression of
      SIRT1 was significantly increased in malignant epithelial tumours compared to
      benign and borderline epithelial tumours (p < 0.001). In particular, a high
      proportion of serous carcinoma expressed SIRT1 (86%, 55/64 cases). Despite the
      frequent expression of SIRT1 in malignant ovarian epithelial tumours, serous
      carcinomas of high FIGO stage showed less frequent SIRT1 expression compared to
      that of low stage serous carcinomas (p = 0.029). Moreover, increased expression
      of SIRT1 in serous carcinoma correlated with increased overall survival by
      univariate (p = 0.014) and multivariate analyses. CONCLUSIONS: Over-expression of
      SIRT1 may play an important role in the early stage of ovarian carcinogenesis.

PMID- 19404851
TI  - Mammary-like gland adenoma of the vulva: review of 46 cases.
AB  - AIMS: Hidradenoma papilliferum (HP) of the anogenital region, which was
      previously thought to be an apocrine tumour, is now believed to be derived from
      anogenital mammary-like glands (MLG) and is more accurately termed MLG adenoma.
      We sought to explore any ramifications that may have resulted from the perceived
      change in histogenesis of this tumour. METHODS: We performed a
      clinicopathological audit of 46 cases. RESULTS: The mean age was 52 years and the
      range 31-90 years. Symptoms occurred in 23%, comprising nodules of increasing
      size 9%, pruritus 9% and bleeding 6%. Tumours occurred in the known distribution
      of mammary-like glands. The labia minora accounted for 50%, labia majora 40%,
      fourchette 7% and clitoris 3%. Tumours were described clinically as cystic in
      42%, ulcerated 33% and solid 25%. Histologically, adjacent normal MLG were often
      present. There was striking diversity in histology. Tubular, papillary, cystic
      and solid areas were seen in various combinations. Two cell types, epithelial and
      myoepithelial, were present. The most common epithelial cell, the ductal cell,
      was seen alone in 43% or associated with apocrine metaplasia (57%) and/or foam
      cells (13%) and/or squamous cells (13%). Myoepithelial cells were usually
      flattened, but were prominent and clear cell in type in 11%. Stroma was variable
      in amount and either desmoplastic or sclerotic. Inflammatory cells were
      particularly associated with tumours involving the surface. Unusual architectural
      patterns resembled breast lesions such as erosive adenomatosis, sclerosing
      adenosis and ductal adenoma. No recurrence or association with malignancy was
      recorded. CONCLUSIONS: MLG adenomas demonstrate a marked diversity in
      histological pattern and cell morphology. The ductal cell and a site compatible
      with and/or the presence of adjacent normal MLG are the most characteristic
      features. Unusual vulvar tumours, which have been previously reported as erosive
      adenomatosis, sclerosing adenosis, papillary adenofibroma, syringocystadenoma
      papilliferans, etc., are variants of MLG adenomas.

PMID- 19404852
TI  - Validation of the revised MDRD formula and the original Cockcroft and Gault
      formula for estimation of the glomerular filtration rate using Australian data.
AB  - AIMS: The estimation of glomerular filtration rate (eGFR) using the MDRD
      (Modification of Diet in Renal Disease) formula is a recommended practice in
      Australia, New Zealand and other countries. Since the original development of
      this formula, an international process to align assays for serum creatinine has
      been undertaken and a revised version of the MDRD formula has been produced for
      these assays. Additionally, the Cockcroft and Gault (C&G) formula remains
      recommended for drug dosing decisions, although there are different versions of
      the formula using either actual weight or calculated ideal body weight. We aimed
      to assess these formulae using Australian data. METHODS: We assessed the revised
      MDRD and the C&G formulae by comparison with radio-isotope GFR measurements using
      patients routinely referred for this test. The MDRD was compared to GFR corrected
      for body surface area and the C&G to the uncorrected GFR. RESULTS: The MDRD was
      shown to have the expected scatter of over +/-30% but with median values not
      significantly different from isotopic GFR measurements and without a systematic
      deviation due to age, gender, height, weight or body mass index (BMI). The
      original C&G formula generally provided a good estimate of GFR, however the use
      of ideal body weight rather than actual body weight produced an under-estimated
      GFR in this population which was more prominent with increasing age and BMI.
      CONCLUSIONS: The MDRD and original C&G formulae were found to be valid in an
      Australian setting. The C&G formula, when calculated using weight estimated from
      patient height, was found to underestimate GFR in some patients.

PMID- 19404853
TI  - Diagnosis of cutaneous melanocytic tumours by four-colour fluorescence in situ
      hybridisation.
AB  - BACKGROUND: Accurate classification of primary melanocytic tumours as benign or
      malignant is crucial for prognostic prediction and appropriate patient
      management. Several chromosomal aberrations have been frequently identified in
      melanomas, but are absent in melanocytic naevi. We performed four-colour
      fluorescence in situ hybridisation (FISH) analysis of melanocytic tumours to
      determine the accuracy of the technique in classifying melanocytic tumours as
      benign or malignant. METHODS: FISH was performed on paraffin-embedded tissue from
      40 histologically unequivocal melanocytic tumours (10 metastatic melanomas, 10
      primary melanomas and 20 benign melanocytic naevi) using the product Vysis LSI
      RREB1/LSI MYB/LSI CCND1/CEP 6 probes (Abbott Molecular Laboratories, USA), which
      is designed to detect the copy number of the RREB1 (6p25), MYB (6q23), and CCND1
      (11q13) genes and FISH positivity is defined by means of a scoring algorithm.
      RESULTS: FISH distinguished the melanomas and the naevi with a sensitivity of 90%
      (10/10 primary melanoma cases and 8/10 metastatic melanoma cases, respectively),
      and a specificity of 95%. The most common abnormalities in the melanomas were
      increased copies of 11q (70%) and 6p (70%), followed by 6q loss relative to cep6
      (50%). Fifteen of the 18 positive melanomas were positive by more than one
      criterion. CONCLUSIONS: The results of this study show that FISH, using a panel
      of four probes, is a sensitive and specific method of classifying benign and
      malignant melanocytic tumours. The four-colour FISH technique has the potential
      to assist in the stratification of the subgroup of melanocytic tumours which are
      difficult to classify using conventional histology.

PMID- 19404854
TI  - Paradoxical effect of Klebsiella pneumoniae OmpK36 porin deficiency.
AB  - AIM: To evaluate the effect of defined mutations in the major OmpK35 and OmpK36
      porins in Klebsiella pneumoniae on the activity of two common plasmid-mediated
      AmpC enzymes. METHODS: Naturally occurring conjugative plasmids containing
      bla(DHA-1) and bla(CMY-2) were obtained from K. pneumoniae isolates in western
      Sydney. These were moved into K. pneumoniae ATCC13883 and isogenic porin
      knockouts Kp885 (DeltaompK35) and Kp886 (DeltaompK36), created by homologous
      recombination of kanamycin resistance cartridges into the specified genes, and
      their antimicrobial susceptibilities compared. RESULTS: beta-lactam resistance
      was greater in the presence of CMY-2-containing plasmids than DHA-1-containing
      plasmids, and higher in K. pneumoniae than Escherichia coli. Neither cefepime nor
      imipenem resistance was observed, and DHA-mediated cefotaxime and
      ticarcillin/clavulanate resistance was unexpectedly reduced from 8-24 (CTX) and
      >256 (TIM) mg/L in Kp13883 to 1-2 (CTX) and 32-48 mg/L (TIM) in the isogenic
      DeltaompK36 porin knockout Kp886. CONCLUSIONS: AmpC plasmids in particular are an
      important cause of transmissible resistance to ticarcillin/clavulanate in K.
      pneumoniae, but probably not in E. coli. Single knockouts of OmpK35 and OmpK36
      porins in K. pneumoniae do not significantly increase antibiotic resistance in K.
      pneumoniae, and a paradoxical lowering of resistance to CTX and TIM is seen with
      deletion of ompK36. This has potentially important clinical implications.

PMID- 19404855
TI  - High throughput detection of microsatellite instability (MSI) in sporadic
      colorectal cancer by MSI COPPER denaturing high performance liquid
      chromatography.

PMID- 19404856
TI  - Frameshift mutation at mononucleotide repeat in ERCC5 in gastric carcinomas with
      microsatellite instability.

PMID- 19404857
TI  - Absence of pro-apoptotic CYTOCHROME C gene mutation in common solid cancers and
      acute leukaemias.

PMID- 19404858
TI  - Gastrointestinal stromal tumour with osteoclast-like giant cells and aneurysmal
      bone cyst-like features.

PMID- 19404859
TI  - Cervical adenocarcinoma metastatic to the ovary mimicking primary ovarian
      carcinoma.

PMID- 19404860
TI  - Florid cystic endosalpingiosis inside a uterine subserous leiomyoma.

PMID- 19404861
TI  - Mixed epithelial and stromal tumour (MEST) of the kidney: a clinicopathological
      report of three cases.

PMID- 19404862
TI  - Transitional cell carcinoma of the urinary tract in renal transplant recipients.

PMID- 19404863
TI  - Primary chondroblastic osteogenic sarcoma of the clavicle: a rare occurrence.

PMID- 19404865
TI  - Erectile dysfunction after prostatectomy: an evaluation of the risk factors.
AB  - OBJECTIVE: The occurrence of erectile dysfunction (ED) in patients who have
      undergone prostatectomy has been assessed in the previous studies; however, its
      rate and risk factors vary in different studies. This study was conducted to
      assess the possible risk factors for ED after prostatectomy. MATERIAL AND
      METHODS: In total, 246 men with benign prostatic hyperplasia (BPH) who were
      candidates for either open prostatectomy or transurethral resection of the
      prostate (TURP) were admitted in this study during a period of 3 years between
      December 2000 and December 2003. Cardiac risk index was assessed before the
      operation using American Heart Association guidelines and erectile function was
      assessed both preoperatively and 6 months after surgery. Patients with moderate
      to severe ED according to the five-item version of the International Index of
      Erectile Function were considered as ED afflicted. In this study, the prevalence
      of preoperative ED, the incidence of postoperative ED, and those conditions that
      could lead to an increase in the incidence of postoperative ED in either
      procedure were determined. RESULTS: The mean age of the patients was 63.7+/-9.7
      years. The prevalence rates of preoperative ED were 24.6% and 25.9% in TURP and
      open prostatectomy groups, respectively. Among patients with no or mild ED
      preoperatively, 12.5% showed moderate to severe ED postoperatively (13.4% in TURP
      group vs 11.25% in open prostatectomy group). CONCLUSIONS: The incidence rate of
      postoperative ED after prostatectomy was 12.5%. Risk factors for its appearance
      included hypertension, diabetes mellitus, higher transfusion rates, higher
      cardiac risk index and an older age.

PMID- 19404864
TI  - Hepatic ethanol elimination kinetics in patients with cirrhosis.
AB  - OBJECTIVE: To address the question of whether increased ethanol elimination in
      alcoholics can be ascribed to increased metabolism via alcohol dehydrogenase
      (ADH; K(m) around 0.2 mM) or the microsomal ethanol-oxidizing system (MEOS; K(m)
      10 mM) by kinetic analysis of hepatic ethanol elimination in recently drinking
      patients with alcoholic cirrhosis and healthy subjects. A further objective was
      to investigate whether systemic clearance of ethanol at low arterial ethanol
      concentrations can be used as a measure of hepatic blood flow. MATERIAL AND
      METHODS: Six patients with alcoholic cirrhosis were enrolled after 2 days of
      abstinence, along with 6 healthy subjects. Ethanol was administered as 6
      successive infusions in increasing doses. Arterial and hepatic venous blood
      concentrations of ethanol were measured; hepatic blood flow was measured
      simultaneously. Kinetic parameters were calculated according to the sinusoidal
      perfusion model of enzymatic elimination by the intact liver. RESULTS: Mean
      hepatic K(m) for ethanol was 0.16 mM (range 0.09-0.36) in healthy subjects and
      0.36 mM (range 0.16-0.69) in patients with cirrhosis (p>0.3), both compatible
      with the K(m) for ADH. The two groups of subjects had similar V(max) values
      (p>0.3). Extrahepatic elimination of ethanol accounted for more than 50% of total
      elimination in both groups, which precludes the use of systemic clearance as a
      measure of hepatic blood flow. CONCLUSIONS: The results support the hypothesis
      that ADH remains the main pathway for hepatic elimination of ethanol in recently
      drinking patients with alcoholic cirrhosis. We interpret this as evidence against
      a significant contribution of MEOS in vivo.

PMID- 19404867
TI  - Mirtazapine and hyperpigmentation.

PMID- 19404868
TI  - Biosynthesis of leukotriene B4 in human polymorphonuclear leukocytes: regulation
      by cholesterol and other lipids.
AB  - Leukotriene B4 (LTB4) is one of the most potent chemotactic compounds produced in
      macrophages and neutrophils. LTB4 is a product of arachidonic acid oxygenation by
      5-lipoxygenase pathway. We present here the data on regulation of LT synthesis in
      human polymorphonuclear leukocytes by cholesterol, cholesterol sulfate and
      cholesterol phosphate. The addition of Pseudomonas aeruginosa lipopolysaccharides
      (LPS) with lipid vesicles containing phosphatidylcholine or
      phosphatidylcholine/cholesterol (70:30) showed that omitting cholesterol
      abolished the effect of LPS on LT synthesis. We show here the capacity of
      cholesterol sulfate, the most abundant sulfated sterol in human blood, to
      suppress LT production in human neutrophils and to neutralize the effect of P.
      aeruginosa LPS on LT synthesis. We suggest that sulfated lipids serve as specific
      endogenous regulators of LT synthesis in neutrophils, and anti-inflammatory
      therapy may be based on modification of cholesterol level and its conversion to
      anionic derivatives.

PMID- 19404869
TI  - Mercury modulates interplay between IL-1beta, TNF-alpha, and gap junctional
      intercellular communication in keratinocytes: mitigation by lycopene.
AB  - Gap junctional intercellular communication (GJIC) is used to control cell
      proliferation. It is not surprising then that a lack of GJIC (i.e., during loss
      of contact inhibition among adjacent cells) is associated with cancer
      promotion/progression. There also seems to be a link between ineffective GJIC and
      increases in inflammatory events. Interestingly, many cytokines released during
      an inflammatory response also have critical roles in cancer cell survival.
      Specifically, TNFalpha and IL-1beta are important for initiating/augmenting
      CD8(+)- and NK-cell mediated killing; however, in what appears counterintuitive,
      each--at times--can act to protect cancer cells against apoptosis, a major
      mechanism for cell killing from within. It is thus plausible to assume that
      certain toxicants might act as cancer promoters in manners distinct
      from/augmentive of direct effects on DNA, i.e., by concurrently altering GJIC and
      cytokine formation in host or microenvironment of a cancer cell. Our research has
      evaluated effects of many toxicants upon keratinocytes; in particular, we have
      examined effects of mercury on GJIC and on TNFalpha and IL-1beta levels in (and
      secretion by) these cells. In the studies here, a tomato preparation (i.e., an
      oleoresin) bearing the antioxidant carotenoid lycopene was examined for its
      effects on GJIC and cytokine formation by keratinocytes in general, and its
      potential ability to mitigate/reverse the toxic effects of mercury in the cells
      in particular. It was shown that a 4-hr treatment with the oleoresin (containing
      56, 6 nM lycopene) re-established GJIC among--and increased the formation of IL
      1beta and TNFalpha that had been significantly reduced within--keratinocytes that
      had been pre-treated for 24 hr with 10 nM HgCl(2). These results show that
      effects of mercury likely depend on some level of oxidative stress and that its
      potential effects on keratinocyte GJIC and cytokine concentrations could, in an
      exposed host, be mitigated/reversed by increased dietary intake of carotenoids
      like lycopene.

PMID- 19404870
TI  - Different regulation of MHC class I antigen processing components in human
      tumors.
AB  - In recent years, progress has been made in understanding how peptides presented
      by MHC Class I molecules were generated, in particular which proteases are
      involved in this process and how intracellular pathways influence antigen
      presentation in professional antigen-presenting cells and various types of tumor
      cells. This review will give an overview of MHC Class I abnormalities in
      malignancies and their underlying molecular mechanisms. Dependent on the tumor
      types structural alterations in particular of the MHC Class I heavy chain,
      beta(2)-m and the TAP1 subunit have been found at a low frequency, whereas
      dysregulation of MHC Class I antigen processing components appears to be the
      major mechanism of MHC Class I down-regulation in tumors of distinct origin. This
      could occur at the epigenetic, transcriptional and/or post-transcriptional level.
      The lack or suppression of MHC Class I surface expression due to antigen
      processing deficiencies are accompanied by reduced recognition and lysis by
      antigen-specific cytotoxic T-lymphocytes, which is further often associated with
      disease progression.

PMID- 19404871
TI  - MHC restriction and allogeneic immune responses.
AB  - Discovery of major histocompatability complex (MHC) restriction helped in the
      understanding of how T-lymphocytes recognize antigens on bacteria, viruses, and
      tumor cells. It was initially accepted that MHC restriction was a consequence of
      "adaptive differentiation" in the thymus; during differentiation, the forming
      repertoire of T-lymphocytes "learned" a low affinity for self MHC molecules via
      positive selection. This view was later countered by discovery of artifacts in
      underlying studies and the fact that adaptive differentiation could not explain
      direct allogeneic and allorestricted recognition phenomena. Data from experiments
      with TCR transgenic animals, individual MHC/peptide complex expression, and
      recipients of xenogenic thymus glands yielded evidence of an ability to adapt to
      microenvironment and a low specificity of positive selection. These facts led to
      an alternative interpretation of MHC restriction explained, in part, by
      specificity of a pool of effector cells activated by primary immunization.
      Details of this phenomenon were defined in studies that noted differential
      primary structures of peptides that bound various allelic forms of MHC molecules.
      Here, the T-lymphocyte repertoire formed in the thymus was a result, in part, of
      random rearrangement of germinal sequences of TCR gene fragments. Such pre
      selected repertoires were inherently capable of reacting with different allelic
      forms of MHC molecules. In contrast, MHC molecules were characterized by
      significant intraspecies polymorphisms; negative and positive selections were
      aimed at adaptation of a pre-selected repertoire to a specific microenvironment
      in an individual. Via elimination of autoreactive clones and sparing of a broad
      spectrum of specificity to potential pathogens, selection in the thymus could be
      considered a life-long allogeneic reaction of a pre-selected repertoire to self
      MHC molecules resulting in tolerance to "self," increased responsiveness to
      foreign MHC molecules, and cross-reactivity of the mature T-lymphocyte repertoire
      to individual foreign peptides plus self MHC.

PMID- 19404872
TI  - Gene expression changes in the mesenteric lymph nodes of rats after oral peanut
      extract exposure.
AB  - New techniques are needed to broaden the understanding of the food allergic
      response. The capacity of peanut extract to influence gene expression profiles
      was investigated in a Brown Norway rat model for food allergy. Brown Norway rats
      were sensitized to peanut extract (0, 1 and 10 mg/rat/d) by daily oral gavage and
      were dissected after 3, 7 or 14 days of exposure. RNA extracted from mesenteric
      lymph nodes of individual rats were hybridized against a common reference pool on
      Agilent whole rat genome (4*44k) arrays. The raw data were normalized and
      statistically analyzed using the statistical program R. A False Discovery Rate of
      10% and a Fold Ratio of - 1.5 < or = Fold Ratio or Fold Ratio > or = 1.5 between
      the experimental groups and their respective control groups were applied.
      Differentially expressed genes were clustered into a heatmap. Functional
      annotation and GeneOntology term enrichment were examined. Furthermore, the
      involvement of the differentially expressed genes in specific cellular pathways
      was investigated with MetaCore. Gene expression changes, which were both dose-
      and time-dependent, were detected after sensitization to peanut. A total of 64
      genes were differentially expressed, of which 60 were up-regulated and four were
      down-regulated. These changes were related to the regulation of immunological
      processes, most notably increased cell division. The findings indicate that
      responses to peanut include proliferation of immunologically relevant tissues,
      which can be identified by analysis of gene expression profiles. This may lay a
      basis for further research into possibilities for discrimination of allergenic
      from non-allergenic proteins.

PMID- 19404873
TI  - Recent progress and diverse effects in developmental immunotoxicology: overview
      of a symposium at the 46th Annual SOT Meeting, Charlotte, NC.
AB  - It has long been known that the developing immune system is more sensitive and
      susceptible than the adult immune system to some drugs and environmental
      contaminants. However, notable advances have been made in the database of studies
      supporting developmental immunotoxicity (DIT) over the past 5 years. There is
      considerable evidence that responses of the immune system can be quantitatively
      or qualitatively different from normal adult responses when xenobiotic exposure
      occurs during critical periods of immune system development. Qualitative
      differences of DIT relative to adult exposures include examples of more
      persistent effects, a latency of effects, and immune dysfunction that is
      fundamentally different than effects observed when adults are exposed. A
      symposium was presented at the Society of Toxicology annual meeting to provide an
      update on advances in the maturing field of developmental immunotoxicology and to
      facilitate discussion on the range of DIT and later life effects following
      developmental exposure. In particular, presentations focused on implications of
      neuroendocrine cross-talk for DIT, the association between developmental air
      pollutant exposure and asthma, and recent evidence that developmental exposure to
      2,3,7,8-tetrachlorodibenzo-p-dioxin may increase the risk of autoimmune
      responses. Several important concepts relative to DIT assessment were
      illustrated, i.e., (1) Screening for immunosuppression alone is not sufficient to
      identify all potential immunotoxic effects; (2) DIT cannot be reliably predicted
      from studies that only utilize adult exposures; (3) Functional testing protocols
      are preferred in the assessment of DIT; (4) Gender-related differences should be
      routinely assessed; (5) Latency (i.e., later-life adverse outcomes resulting from
      developmental exposures) is an important consideration that cannot be detected in
      adult exposure studies; and, (6) There is increasing support for DIT testing
      protocols with continuous exposure throughout development until the immune assay
      is performed.

PMID- 19404874
TI  - Developmental immunotoxicology (DIT): windows of vulnerability, immune
      dysfunction and safety assessment.
AB  - Developmental immunotoxicity (DIT) is an increasing health concern since DIT
      outcomes predispose children to those diseases that have been on the rise in
      recent decades (e.g., childhood asthma, allergic diseases, autoimmune conditions,
      childhood infections). The enhanced vulnerability of the developing immune system
      for environmental insult is based on unique immune maturational events that occur
      during critical windows of vulnerability in early life. The semi-allogeneic
      pregnancy state, with suppression of graft rejection and associated skewing of
      the fetal and neonatal immune system, also influences the specific nature of DIT
      outcomes. In the exposed offspring, targeted immunosuppression can co-exist with
      an increased risk of allergic and/or autoimmune disease. Because with DIT immune
      dysfunction rather than profound immunosuppression is the greater concern,
      testing approaches should emphasize multi-functional assessment. Beyond T-cells,
      dendritic cells and macrophages are sensitive targets. The last-trimester fetus
      and the neonate are normally depressed in T(H)1-dependent functions and postnatal
      acquisition of needed T(H)1 capacity is a major concern with DIT. With this in
      mind, assessment should include a measure of T(H)1-dependent cell-mediated
      immunity [cytotoxic T-lymphocyte (CTL) activity or delayed-type hypersensitivity
      (DTH) response] in conjunction with a multi-isotype T-dependent antibody response
      (TDAR) and evaluation of innate immunity (e.g., NK activity). Other parameters
      such as immune histology, immunophenotyping, cytokine responses, and organ
      weights can be useful when included with immune functional evaluation. A
      multifunctional DIT protocol using influenza challenge is presented as one
      example of an approach that permits dysfunction and misregulation to be
      evaluated.

PMID- 19404875
TI  - Perinatal TCDD exposure and the adult onset of autoimmune disease.
AB  - Modulation of the developing immune system can occur following perinatal exposure
      to a number of immunotoxic compounds, including polyhalogenated hydrocarbons like
      2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD; dioxin), the most toxic of the
      congeners. Studies in rodents have shown immunologic effects from perinatal TCDD
      exposure are more severe and persistent than following exposure in the adult, and
      include what appears to be life-long immunosuppression. Whether prenatal TCDD
      exposure may predispose an individual to postnatal autoimmune disease remains
      largely unknown. TCDD crosses the placenta and alters normal prenatal thymocyte
      maturation, T-cell receptor expression and expression of thymic major
      histocompatability complex Class II molecules. During the juvenile stage, mice
      exposed to TCDD prenatally show increased peripheral T-cells possessing
      "autoreactive" variable-beta receptors. These data suggest that gestational
      exposure to TCDD may interfere with normal development of central tolerance in
      the thymus. In possible support of this theory, when autoimmune disease-prone
      mice were treated with TCDD during gestation, postnatal autoimmunity had an
      accelerated onset and was exacerbated. This review provides an overview of the
      currently available information, which appears to support a hypothesis for
      increased risk of postnatal autoimmune responses as a result of TCDD exposure
      during the sensitive time of immune system establishment.

PMID- 19404876
TI  - Maternal and early life stress effects on immune function: relevance to
      immunotoxicology.
AB  - Stress is triggered by a variety of unexpected environmental stimuli, such as
      aggressive behavior, fear, forced physical activity, sudden environmental
      changes, social isolation or pathological conditions. Stressful experiences
      during very early life (particularly, maternal stress during fetal ontogeny) can
      permanently alter the responsiveness of the nervous system, an effect called
      programming or imprinting. Programming affects the hypothalamic-pituitary
      adrenocortical (HPA) axis, brain neurotransmitter systems, sympathetic nervous
      system (SNS), and the cognitive abilities of the offspring, which can alter
      neural regulation of immune function. Prenatal or early life stress may
      contribute to the maladaptive immune responses to stress that occur later in
      life. This review focuses on the effect of maternal and early life stress on
      immune function in the offspring across life span. It highlights potential
      mechanisms by which prenatal stress impacts immune functions over life span. The
      literature discussed in this review suggests that psychosocial stress during pre-
      and early postnatal life may increase the vulnerability of infants to the effects
      of immunotoxicants or immune-mediated diseases, with long-term consequences.
      Neural-immune interactions may provide an indirect route through which
      immunotoxicants affect the developing immune system. A developmental approach to
      understanding how immunotoxicants interact with maternal and early life stress
      induced changes in immunity is needed, because as the body changes
      physiologically across life span so do the effects of stress and immunotoxicants.
      In early and late life, the immune system is more vulnerable to the effects of
      stress. Stress can mimic the effects of aging and exacerbate age-related changes
      in immune function. This is important because immune dysregulation in the elderly
      is more frequently and seriously associated with clinical impairment and death.
      Aging, exposure to teratogens, and psychological stress interact to increase
      vulnerability and put the elderly at the greatest risk for disease.

PMID- 19404877
TI  - Immunotoxicologic analysis of maternal transmission of asthma risk.
AB  - Asthma has origins in early life. Epidemiological studies show that maternal,
      more than paternal, asthma significantly increases a child's risk of developing
      the disease. Experimental animal models exist which reproduce the increased
      susceptibility to asthma seen in human studies, and allow analysis of immunotoxic
      mechanisms that may contribute to neonatal allergy. In addition to maternal
      asthma, chemically-induced skin contact hypersensitivity or exposure during
      pregnancy of non-allergic females to certain environmental agents, e.g., air
      pollution particles, can also result in increased susceptibility to asthma in
      their offspring. We review here experimental models of maternal transmission of
      asthma risk, the progress to date in identifying mechanisms, and potential
      directions for future research.

PMID- 19404879
TI  - Globalizing Chinese medicine. Introductory note.

PMID- 19404880
TI  - Chinese propriety medicines: an "alternative modernity?" The case of the anti
      malarial substance artemisinin in East Africa.
AB  - This article discusses various modes of "modernizing" traditional Chinese medical
      drugs (zhongyao [image: see text]) and transforming them into so-called Chinese
      propriety medicines (zhongchengyao [image: see text]) that are flooding the
      current neoliberal wellness markets. This article argues that the chemical
      procedures used in the manufacture of Chinese propriety medicines are highly
      culture-specific and deserve being considered as instantiations of an
      "alternative modernity" (e.g., Knauft 2002), rather than of "Westernization."
      These Western-Chinese combinations, produced in strife toward fulfilling Mao
      Zedong's Communist-revolutionary vision, have a potential to represent a critical
      alterity to Western health policies, challenging rhetoric against such
      combinations. However, as is also noted in this article based on ethnographic
      fieldwork in East Africa, their potential alterity has been corroded for at least
      two reasons. First, the medical rationale for dispensing these medications has
      been shaped by commercial demands in ways that have worked toward transforming
      the formerly scholarly Chinese medical tradition (as outlined by Bates 1995) into
      a consumer-near and popular "folk medicine" (as defined by Farquhar 1994:212).
      Second, the repertoire of Chinese propriety medicines is impoverished as its
      efficacious "alternatively modern" drugs are being redefined as "modern"
      biomedical drugs. The article concludes that the potentially critical alterity of
      any formerly scholarly traditional medicine is more likely to be lost in those
      fields of health care that are both highly commercialized and polarized by the
      biomedical imperative to distinguish between "traditional" and "modern"
      medicines. As example for demonstrating how contentious the issue is, qinghaosu
      [image: see text] (artemisinin) is put center stage. It is an anti-malarial
      substance which in the 1970s Chinese scientists extracted from the Chinese
      medical drug qinghao [image: see text] (Herba Artemisiae annuae). Some Chinese
      practitioners in East Africa argued that artemisinin belonged among the Chinese
      propriety medicines they sold. Although according to Western biomedical criteria
      and the Chinese scientists who were involved in its chemical identification,
      artemisinin is a "modern" Western drug, their polemics deserve to be more closely
      analyzed as what social scientists have recognized as an "alternative modernity."

PMID- 19404878
TI  - Acculturation, physical activity, and obesity among Hispanic adolescents.
AB  - OBJECTIVE: Little is known about how acculturation may influence participation in
      leisure-time physical activity and obesity among adolescents. The objective of
      this study was to examine these associations among Hispanic adolescents. DESIGN:
      Data were drawn from the 2003 National Survey of Children's Health, restricted to
      Hispanic adolescents aged 10-17 (n=4704). Acculturation was assessed by proxy
      measures (generation status and language spoken at home). Adolescents who were
      not reported to engage in physical activity lasting at least 20 minutes, that was
      vigorous enough to cause sweating and hard breathing, for at least three days per
      week were defined as failing to meet physical activity requirements. Obesity was
      defined as gender and age-specific body mass index values at or above the 95th
      percentile of the reference population. Multiple logistic regressions were
      performed to adjust for confounders. RESULTS: Of the Hispanic adolescents
      studied, 25.2%, 43.8%, and 31.1% were first, second, and third generation or
      more, respectively. English was the primary language in the home for 42.8% of
      these adolescents. Compared with adolescents in the third generation, adolescents
      from immigrant families had higher odds for not obtaining recommended physical
      activity (first generation: adjusted odds ratio [AOR] = 1.50, 95% conference
      intervals [CI]: 1.09, 2.05; second generation: AOR = 1.29, 95% CI: 0.99, 1.69).
      Living in homes where English was not the primary language, vs. English-speaking
      homes, was also associated with not obtaining recommended physical activity (AOR
      = 1.36, 95% CI: 1.06, 1.75). The unadjusted prevalence of obesity was higher in
      homes where English was not the primary language (22.5% vs. 16.1%; p<0.01), but
      this difference disappeared after adjusting for family socioeconomic status.
      Generational status was not a significant correlate of obesity. CONCLUSIONS:
      Findings suggest that future public health interventions that aim to increasing
      physical activity among Hispanic adolescents should be tailored based on
      generational status and English-language use.

PMID- 19404881
TI  - Practitioner decisions to engage in Chinese medicine: cultural messages under the
      skin.
AB  - Theories of agency and decision making have been applied to processes by which
      patients select therapeutic interventions. Another kind of decision making occurs
      when individuals choose to engage in the practice of a therapeutic modality. This
      article draws on fieldwork and interview data with non-Chinese and immigrant
      Chinese practitioners of Chinese medicine in the United States, focusing on
      Boston, Massachusetts, and New York City, as case illustrations. I apply theories
      of agency and decision making to how and why these practitioners chose to engage
      in Chinese modalities. I build on Volker Scheid's (2002) analysis of agency,
      grounded in Chinese medicine theory, to propose the Chinese concept of xin
      ([image: see text] heart-mind) as an analytical frame, suggesting that it can
      fruitfully be set in tension with Pierre Bourdieu's notion of habitus and Antonio
      Gramsci's discussion of the "common-sense" nature of hegemony. I draw on a non
      Eurocentric concept to enrich the theoretical discussion of agency and decision
      making.

PMID- 19404882
TI  - A doctor of the highest caliber treats an illness before it happens.
AB  - "A doctor of the highest caliber treats an illness before it happens," a
      seemingly antiquated doctrine in traditional Chinese medicine, is enjoying
      surging popularity among practitioners in urban China and the United States
      today. In this essay, I examine how the meanings and contours of traditional
      Chinese medicine have shifted in recent decades as it is molded into a
      "preventive medicine" through translocal encounters. From the 1960s and the early
      1970s, the emphasis China's socialist health care placed on preventive health
      among the rural poor shaped the practice of Chinese herbal medicine and
      especially acupuncture. This version of preventive medicine was also exported to
      the Third World, which China strove to champion. Since the end of the Cold War
      and especially during the 1990s, as China strives to "get on track with the
      world" (specifically, affluent nation-states, especially in North America and the
      European Union), traditional Chinese medicine has been rapidly commodified and
      reinvented as a new kind of preventive medicine tailored for cosmopolitan, middle
      class lifestyles. The emergence of this radically new preventive medicine
      resuscitates certain stories of antiquity and continuity, emphasizing that
      traditional Chinese medicine has always been "preventive" while obliterating
      recent memories of the proletariat world and its preventive medicine.

PMID- 19404883
TI  - Which pedagogical principles should clinical teachers know? Teachers and
      education experts disagree. Disagreement on important pedagogical principles.
AB  - BACKGROUND: In a previous study, a group of non-clinician medical education
      experts identified 30 pedagogical principles, knowledge of which might enhance
      clinical teaching effectiveness. AIMS: To assess expert teachers? perceptions of
      which basic pedagogical principles, if known and understood, would enhance their
      teaching effectiveness. METHOD: We conducted an on-line Delphi consensus-building
      study with 25 expert clinical teachers who rated the importance to teaching
      effectiveness of each of the 30 principles. RESULTS: There was agreement between
      clinicians and PhD education experts on the importance of several of the
      principles but there was major disagreement between the 2 groups for many
      principles, including those related to assessment and those relevant to clinical
      teachers? day to day teaching activities. CONCLUSIONS: The lack of concordance
      between clinical teachers and education experts with respect to how the 30
      principles rank in importance may have serious implications for faculty
      development and for the design, development, and assessment of educational
      programs. Program directors and curriculum designers should exploit the strengths
      of both clinician and non-clinician educators to assure the success of
      educational programs.

PMID- 19404884
TI  - Domains of effective teaching process students perspectives in two medical
      schools.
AB  - BACKGROUND: There has been little systematic investigation of student belief
      about the characteristics of the optimum process for clinical bedside teaching.
      AIMS: The intent was to identify the most important characteristics of the
      bedside teaching experience from the perspective of two groups of students, one
      from Oman and the other from Canada. METHOD: Students were asked to complete a
      questionnaire about their concept of the ideal process of bedside teaching. Their
      answers were analyzed using factor analysis. RESULTS: Answers provided by the
      students was consistent with the presence of six domains. These corresponded to
      Preparation, Introduction, Experience, Summary, Explanation, and Conclusion.
      'Preparation' involves consideration of the patient and the knowledge level of
      the learners, 'Introduction' involves effective communication, and 'Experience'
      means the need for the students to be actively involved in the history and
      physical examination. The remaining three domains deal with the need to provide a
      summary and elaboration as well as advice and feedback. These 6 factors explained
      60% of the total variance. CONCLUSIONS: While these areas still need to be
      defined more closely, the application of these six domains to the structure of
      the bedside teaching experience is likely to result in improved student learning.

PMID- 19404885
TI  - Still far to go--an investigation of gender perspective in written cases used at
      a Swedish medical school.
AB  - OBJECTIVE: Given decisions to implement a gender perspective in medical
      education, this study investigated gender perspective in written cases used at a
      Swedish medical school. METHOD: All course organizers on terms 5-11 were asked to
      submit the case descriptions used in 2005. The 257 cases collected were subjected
      to content analysis focussing on sex of author and patient; whether there were
      any guidelines for tutors; and whether the case touched on biological sex
      differences, psychosocial and gender aspects. RESULTS: The majority of cases were
      written by male teachers. The proportions of male and female patients were equal.
      There were instructions for tutors in 20% of the cases. Sex differences were
      mentioned in 7% of cases. Psychosocial data were meager. Ten cases (4%) contained
      gender aspects and four of them presented gender as a main issue. CONCLUSIONS:
      The lack of instructions for tutors and overall scant interest in psychosocial
      issues were important obstacles for gender implementation. Actually, ignoring
      psychosocial conditions means that a gender perspective is also neglected. The
      results illuminate the importance of monitoring and follow-ups for a successful
      implementation of gender. Our method of scrutinizing written cases might be
      useful also for other medical schools.

PMID- 19404886
TI  - Learning intimate examinations with simulated patients: the evaluation of medical
      students' performance.
AB  - BACKGROUND: For fifth-year's undergraduates of the medical school, a project with
      simulated patients (Intimate Examination Associates, IEA) was implemented in 2002
      at the University of Antwerp. In this project, students from the new curriculum
      (NC) learned uro-genital, rectal, gynaecological and breast examination in
      healthy, trained volunteers and received feedback focused on personal attitude,
      technical and communication skills. Former curriculum (FC) students however
      trained these skills only during internship in the sixth year after a single
      training on manikins. AIMS: This study assessed the effect of learning intimate
      examinations with IEA's by comparing students from FC and NC on four different
      outcome parameters. METHODS: Three groups were compared: FC after internships
      without IEA training, NC after internships with IEA training and fifth year NC
      immediately after the IEA training. Four assessment instruments: an OSCE using
      checklists and global rating scales to assess the technical skills, a score list
      on students attitudes and performance filled in by the IEA's, a student
      questionnaire on self-assessed competence and a questionnaire on the frequency of
      performing intimate skills during internships. RESULTS: Both NC groups scored
      globally better in the OSCE (significance for male examination). Sub-scores for
      'completeness' and 'systematic' approach was significantly higher in both NC
      groups for male and female examinations. NC students reported better self
      assessed competence and performance concerning gynaecological and urological
      clinical and communication skills during internship. The best results were
      obtained after IEA training and internship was done for the four outcomes. IEA's
      are influenced by the 'experienced' students after internship: FC and NC after
      internship both scored better than the fifth year NC who only received the IEA
      training so far. CONCLUSION: Learning intimate examinations with IEA's has a
      positive effect on the performance of medical students. This beneficial effect is
      on its turn reinforced during internships.

PMID- 19404887
TI  - Resident run journal club: a model based on the adult learning theory.
AB  - BACKGROUND: Multiple formats of journal club exist but data is lacking regarding
      which model is most effective. Many residents are dissatisfied with their current
      format, which was the case at our institution. AIM: This article discusses a
      resident run model, residents' perceptions following its implementation, and
      recommendations for running a successful journal club. Practice points Journal
      club formats vary extensively without a clearly superior method. Defining goals
      is the first step to a successful journal club. Structured review instruments for
      articles enhance journal club. The presence of subspecialty staff may augment
      learning. Resident-run models of journal club can be successfully implemented.
      METHODS: A resident run model of journal club was developed based on Adult
      Learning Theory. A 30-question survey was created to assess residents' attitudes
      and satisfaction with the new model. RESULTS: All respondents preferred the new
      model compared to the old model. Residents reported the new model increased their
      medical knowledge (88%) and they were able to apply the methods learned in
      journal club to actual patients (82%). CONCLUSIONS: A resident run model of
      journal club may be a viable option for those attempting to start or improve
      their current club.

PMID- 19404888
TI  - Is a web-based concordance test feasible to assess therapeutic decision-making
      skills in a French context?
AB  - BACKGROUND: At the end of undergraduate medical curriculum, a written simulation
      based examination is used in France to assess therapeutic decision-making skills
      and to rank students for the purpose of matching their training specialties.
      However, this examination based on a single assessment method remains a subject
      of debate. AIM: To study the feasibility of a web-based Concordance test for
      therapeutic decision-making assessment. METHODS: A 12 clinical-case Concordance
      test was developed based on objectives for the undergraduate training program.
      The test was administered on line to candidates with different levels of clinical
      experience. Fifteen therapeutic teachers constituted the reference panel. Data
      analysis included analysis of variance, post-hoc test, and Cronbach's alpha.
      RESULTS: One hundred and seventy participants (113 students, 34 residents, 23
      physicians) fully completed the free-access test on line with no technical
      problems. Differences between the mean scores for groups were significant (p <
      0.001). Significant differences occurred between fourth year students and
      residents (p < 0.001), fourth year students and physicians (p = 0.001). No
      difference was found between residents and physicians. Reliability coefficient
      was 0.67. CONCLUSION: A web-based Concordance test in the field of therapeutic
      decision-making was considered feasible in a French learning environment. Further
      research is warranted to determine its usefulness as a part of the National
      Examination.

PMID- 19404889
TI  - Portfolio critics: do they have a point?

PMID- 19404890
TI  - The effectiveness of portfolios for post-graduate assessment and education: BEME
      Guide No 12.
AB  - BACKGROUND: Portfolios in post-graduate healthcare education are used to support
      reflective practice, deliver summative assessment, aid knowledge management
      processes and are seen as a key connection between learning at organisational and
      individual levels. This systematic review draws together the evidence on the
      effectiveness of portfolios across postgraduate healthcare and examines the
      implications of portfolios migrating from paper to an electronic medium across
      all professional settings. METHODS: A literature search was conducted for
      articles describing the use of a portfolio for learning in a work or professional
      study environment. It was designed for high sensitivity and conducted across a
      wide range of published and unpublished sources relevant to professional
      education. No limits for study design or outcomes, country of origin or language
      were set. Blinded, paired quality rating was carried out, and detailed appraisal
      of and data extraction from included articles was managed using an online tool
      developed specifically for the review. Findings were discussed in-depth by the
      team, to identify and group pertinent themes when answering the research
      questions. RESULTS: Fifty six articles from 10 countries involving seven
      healthcare professions met our inclusion criteria and minimum quality threshold;
      mostly uncontrolled observational studies. Portfolios encouraged reflection in
      some groups, and facilitated engagement with learning. There was limited evidence
      of the influence of a number of factors on portfolio use, including ongoing
      support from mentors or peers, implementation method, user attitude and level of
      initial training. Confounding variables underlying these issues, however have not
      been fully investigated. A number of authors explored the reliability and
      validity of portfolios for summative assessment but reports of accuracy across
      the disparate evidence base varied. Links to competency and Quality Assurance
      frameworks have been demonstrated. There were conflicting reports about whether
      the different purposes of portfolios can be combined without compromising the
      meaningfulness of the contents. There was good evidence that the flexibility of
      the electronic format brought additional benefits to users, assessors and
      organisations, and encouraged more enthusiastic use. Security of data remained a
      high priority issue at all levels, and there was emerging evidence of successful
      transfer between electronic portfolio systems. CONCLUSION: The evidence base is
      extensive, but contains few high quality studies with generalisable messages
      about the effectiveness of portfolios. There is, however, good evidence that if
      well implemented, portfolios are effective and practical in a number of ways
      including increasing personal responsibility for learning and supporting
      professional development. Electronic versions are better at encouraging
      reflection and users voluntarily spend longer on them. Regular feedback from a
      mentor enhances this success, despite competing demands on users' time and
      occasional scepticism about the purpose of a portfolio. Reports of inter-rater
      reliability for summative assessments of portfolio data are varied and there is
      benefit to be gained from triangulating with other assessment methods. There was
      insufficient evidence to draw conclusions on how portfolios work in
      interdisciplinary settings.

PMID- 19404891
TI  - The educational effects of portfolios on undergraduate student learning: a Best
      Evidence Medical Education (BEME) systematic review. BEME Guide No. 11.
AB  - INTRODUCTION: In recent years, the use of portfolios as learning and assessment
      tools has become more widespread across the range of health professions. Whilst a
      growing body of literature has accompanied these trends, there is no clear
      collated summary of the evidence for the educational effects of the use of
      portfolios in undergraduate education. This systematic review is the result of
      our work to provide such a summary. METHODS: We developed a protocol based on the
      recommendations of the Best Evidence Medical Education (BEME) collaboration.
      Citations retrieved by electronic searches of 10 databases were assessed against
      pre-defined inclusion/exclusion criteria by two independent reviewers and full
      texts of potentially relevant articles were obtained. Studies were identified for
      inclusion in the review by examination of full text articles by two independent
      reviewers. At all stages, discrepancies were resolved by consensus. Data relating
      to characteristics of the student population, intervention, outcome measures,
      student design and outcomes were collected using a piloted data extraction form.
      Each study was assessed against 11 quality indicators designed to provide
      information about how well it was designed and conducted; and against the
      Kirkpatrick hierarchy as modified for educational settings. Comparisons between
      different groups were carried out using the Kruskal-Wallis test (non-parametric
      ANOVA) or the Mann-Whitney U test as appropriate. RESULTS: Electronic searches
      yielded 2,348 citations. A further 23 citations were obtained by hand searching
      of reference lists. About 554 full articles were retrieved and assessed against
      our inclusion criteria. Of the 69 studies included in our review, 18 were from
      medicine, 32 from nursing and 19 from other allied health professions, including
      dentistry, physiotherapy and radiography. In all professional groups, portfolios
      were used mainly in the clinical setting, completion was compulsory, reflection
      required and assessment (either formative, summative or a combination of both)
      the norm. Three studies used electronic portfolios. Whilst many studies used a
      combination of data collection methods, over half of all included studies used
      questionnaires, a third used focus group interviews and another third used direct
      assessment of portfolios. Most studies assessed student or tutor perceptions of
      the effect of the use of portfolios on their learning. Five studies used a
      comparative design, one of which was a randomized controlled trial. Studies were
      most likely to meet the quality indicators relating to appropriateness of study
      subjects, clarity of research question and completeness of data. However, in many
      studies, methods were not reported in sufficient detail to allow a judgement to
      be made. About 19 of the 69 included studies (27%) met seven or more quality
      indicators. Across all professions, such 'higher quality' studies were more
      likely to have been published recently. The median 'quality score' (number of
      indicators met) rose from two for studies published in 2000 or earlier to seven
      for studies published in 2005 or later. Significant differences were observed
      between the quality scores for studies published in or before 2000 and those
      published between 2001 and 2004 (p = 0.027), those published in or before 2000
      and those published in 2005 or later (p = 0.002) and between all studies (p =
      0.004). Similar trends were seen in all professional groups. About 59 (85%) of
      the included studies were assessed at level 1 of the modified Kirkpatrick
      hierarchy (i.e. 'participation' effects, including 'post hoc' evaluations of
      student perceptions of the effects of keeping a portfolio on their learning).
      About 9 (13%) of the studies reported direct measurement of changes in student
      skills or attitudes and one study reported a change in student behaviour. The
      main effects of portfolio use identified by the included studies were:
      Improvement in student knowledge and understanding (28 studies, six at
      Kirkpatrick level 2 or above), greater self-awareness and encouragement to
      reflection (44 studies, seven at Kirkpatrick level 2 or above) and the ability to
      learn independently (10 studies, one at Kirkpatrick level 2). The findings of
      higher quality studies also identified benefits in these areas. They reported
      improved student knowledge and understanding, particularly the ability to
      integrate theory with practice, although a correlation with improved scores in
      other assessments was not always apparent. Greater self-awareness and engagement
      in reflection were also noted, although some studies questioned the quality of
      the reflection undertaken. Higher quality studies also suggest that use of
      portfolios improves feedback to students and gives tutors a greater awareness of
      students' needs, may help students to cope with uncertain or emotionally
      demanding situations and prepares students for postgraduate settings in which
      reflective practice is required. Time commitment required to collate a portfolio
      was the major drawback identified. In two of the studies, this was found to
      detract from other clinical learning. CONCLUSIONS: At present, the strength and
      extent of the evidence base for the educational effects of portfolios in the
      undergraduate setting is limited. However, there is evidence of an improving
      trend in the quality of reported studies. 'Higher quality' papers identify
      improvements in knowledge and understanding, increased self-awareness and
      engagement in reflection and improved student-tutor relationships as the main
      benefits of portfolio use. However, they also suggest that whilst portfolios
      encourage students to engage in reflection, the quality of those reflections
      cannot be assumed and that the time commitment required for portfolio completion
      may detract from other learning or deter students from engaging with the process
      unless required to do so by the demands of assessment. Further work is needed to
      strengthen the evidence base for portfolio use, particularly comparative studies
      which observe changes in student knowledge and abilities directly, rather than
      reporting on their perceptions once a portfolio has been completed.

PMID- 19404892
TI  - Creating effective poster presentations: AMEE Guide no. 40.
AB  - Poster presentations have become an important part of professional meetings and
      are recognized as valuable tools for teaching and assessment. An effective poster
      is a visual communication tool that will help you engage colleagues in
      conversation, convey your main point to large numbers of people, and advertise
      your work. An effective poster is a highly condensed version of a research paper
      constructed primarily of visual displays of data with just enough supporting text
      to provide context, interpretation, and conclusions. A new AMEE Guide, 'Creating
      Effective Poster Presentations', provides guidance and is illustrated with
      annotated examples.

PMID- 19404893
TI  - Evidence-based medicine teaching in UK medical schools.
AB  - BACKGROUND: It is recognized that clinicians need training in evidence-based
      medicine (EBM), however there is considerable variation in the content and
      methods of the EBM curriculum in UK medical schools. AIMS: To determine current
      practice and variation in EBM undergraduate teaching in UK medical schools and
      inform the strategy of medical schools and the National Knowledge Service.
      METHODS: We contacted all 32 medical schools in the UK and requested that the
      person primarily responsible for EBM undergraduate teaching complete a short
      online survey and provide their EBM curriculum. RESULTS: The survey was completed
      by representatives from 20 (63%) medical schools and curriculum details were
      received from 5 (16%). There is considerable variation in the methods and content
      of the EBM curriculum. Although the majority of schools teach core EBM topics,
      relatively few allow students to practice the skills or assess such skills. EBM
      teaching is restricted by lack of curriculum time, trained tutors and teaching
      materials. CONCLUSIONS: Key elements to progress include the integration of EBM
      with clinical specialties, tutor training and the availability of high-quality
      teaching resources. The development of a national undergraduate EBM curriculum
      may help in promoting progress in EBM teaching and assessment in UK medical
      schools.

PMID- 19404894
TI  - Assessment of medical professionalism: who, what, when, where, how, and ... why?
AB  - Medical professionalism is increasingly recognized as a core competence of
      medical trainees and practitioners. Although the general and specific domains of
      professionalism are thoroughly characterized, procedures for assessing them are
      not well-developed. This article outlines an approach to designing and
      implementing an assessment program for medical professionalism that begins and
      ends with asking and answering a series of critical questions about the purpose
      and nature of the program. The process of exposing an assessment program to a
      series of interrogatives that comprise an integrated and iterative framework for
      thinking about the assessment process should lead to continued improvement in the
      quality and defensibility of that program.

PMID- 19404896
TI  - E-learning in medical education: Guide supplement 32.3--practical application.

PMID- 19404895
TI  - E-learning in medical education: Guide supplement 32.2--practical application.
AB  - E-portfolios are often celebrated as the choice of technology to engage students
      and trainees in the personal development processes which underpin their academic
      and professional careers, but the process of portfolio creation cannot work in
      isolation. Research highlights the importance of feedback, relevance and
      assessment in engaging users and encouraging the pedagogical processes which can
      be exploited by the online environment. The use of an e-portfolio needs to be
      embedded firmly into the curriculum and embraced by educators and users alike.

PMID- 19404897
TI  - E-learning in medical education: Guide supplement 32.4--practical application.

PMID- 19404898
TI  - Morbidity in a population of low-income, female users of MDMA and other drugs.
AB  - Few previous studies have reported on the overall health of drug-using women. To
      investigate this, 696 low-income women aged 18-31 were recruited in a cross
      sectional study from gynecological care clinics in Texas between 2001 and 2003.
      Compared to exclusive marijuana users and non-drug users, women who used MDMA and
      those who used other illicit drugs but not MDMA reported more gynecological
      conditions, medical conditions, depressive symptoms, and physical somatic
      complaints. We concluded that young, low-income women who used more than one
      illicit drug experience significantly more physical and psychological morbidity.
      Generalization of this study results may be limited to young women with low
      income but not to other populations.

PMID- 19404899
TI  - Warfarin-associated fetal intracranial hemorrhage in woman with mitral valve
      replacements: a case report.
AB  - Warfarin-associated fetal hemorrhage is a fatal event. We report the case of a 39
      year-old woman who had been taking warfarin for 23 years since undergoing mitral
      valve replacement. Thereafter, when she was found to be pregnant, the medication
      was switched to heparin from 6 to 21 weeks of gestation. Following this, she was
      prescribed oral warfarin again (3.5 mg per day), with a strict control of
      prothrombin time/international normalized ratio (PT/INR). At 23 weeks of
      gestation, fetal intracranial hemorrhage occurred because of maternal exposure to
      warfarin. Maternal PT/INR does not correlate well with the activity of warfarin
      in the fetus and currently, there is no direct way to prevent fetal intracranial
      hemorrhage. Hence, further research on the optimal coagulation therapy in
      pregnant women with valve replacement should be encouraged.

PMID- 19404900
TI  - Outpatient oral misoprostol for prolonged pregnancies: a pilot investigation.
AB  - We evaluated the effectiveness of oral misoprostol for outpatient cervical
      ripening and labor induction in prolonged pregnancies. We performed a randomized,
      double-blind, placebo-controlled study of women at 40 to 42 weeks' gestation with
      well-dated pregnancies, singleton gestations, Bishop scores less than 6, vertex
      presentations, and intact membranes. Subjects received either oral misoprostol
      100 microg or placebo daily for 3 days unless the subject developed significant
      cervical change or began labor spontaneously. Study drug was repeated every 24
      hours for a maximum of three doses if subjects did not develop significant
      cervical change or enter labor. Induction of labor was not allowed while the
      subject was enrolled in the study. Forty-three subjects were randomized to
      receive misoprostol and 44 randomized to receive placebo. A significant
      difference was noted in reduction of time from study entry to both active phase
      (p < 0.001) and delivery (p < 0.001) in the misoprostol group. Fewer women
      remained undelivered after the 72-hour study period in the misoprostol group.
      There were no differences in route of delivery or neonatal outcomes between
      groups. CONCLUSION: Daily administration of oral misoprostol over 3 days to women
      with prolonged pregnancies shortened time intervals from dosing to entry into
      active labor and delivery compared with placebo.

PMID- 19404901
TI  - [Anatomical considerations on treatment strategies for compression syndromes of
      the fibular nerve in the proximal leg].
AB  - BACKGROUND: Posttraumatic or iatrogen compression syndromes of the common fibular
      nerve (CFN) are frequent. Based on previous anatomical investigations the aim of
      this study was to analyse the course of the CFN along the proximal portion of the
      leg with respect to its relationship to the anterior intermuscular septum (AIS).
      Further sites of constriction or fibrous fixation should be defined. MATERIAL AND
      METHODS: Anatomical dissection of 111 cadaveric leg specimens was performed.
      Twenty additional legs were used for histological examination of the respective
      region within the AIS of the leg. By means of medical records of three patients
      our current treatment strategy is demonstrated. RESULTS: A tight fixation of the
      most proximal motor branch of the deep fibular nerve (DFN) within the AIS at its
      entering point to the anterior compartment could be demonstrated. CONCLUSION: We
      conclude, that selective decompression not only of the CFN, but of the DFN
      branches which are fixed in the AIS along their course through the proximal
      portion of the leg, is mandatory during compression syndromes of the CFN.

PMID- 19404903
TI  - [High resolution CT (HRCT) imaging findings in hypersensitivity pneumonitis]

PMID- 19404902
TI  - [The study of medicine today: patient actors and "hammer examination"].

PMID- 19404904
TI  - [Fatigue].

PMID- 19404905
TI  - [What is your diagnosis?].

PMID- 19404906
TI  - [Percutaneous aortic valve replacement in high risk patients].
AB  - The degenerative, calcified aortic stenosis is the most common form of adult
      valvular heart disease. Surgical aortic valve replacement is the method of choice
      and can be performed at low risk in suitable candidates. However, a fair amount
      of patients is rejected from surgery due to old age and preexisting comorbidities
      increasing operative mortality. For this reason frequently operation is not
      accomplished. Today, with the development of percutaneous aortic valve
      replacement, the treatment of aortic stenosis has entered a new era providing a
      new durable treatment option.

PMID- 19404907
TI  - [New therapeutic opportunities in metastatic renal cell carcinoma].
AB  - Until recently metastatic renal cell carcinoma was considered refractory to the
      available therapies. A better understanding of the molecular biology and the
      introduction of targeted agents led to a significant improvement in the prognosis
      of patients with metastatic renal cell carcinoma. In this paper the molecular
      pathology, specifically the deregulation of the oxygen adaption mechanisms
      leading to tumorangiognesis will be presented. Based on these fundamental
      mechanisms the targeted agents will be introduced. These agents have been tested
      in randomized phase III trials in different clinical and prognostic situations.
      The results and the side-effects of sunitinib, sorafenib, temsirolimus,
      everolimus and bevacizumab treatment will be presented leading to a possible
      treatment algorithm.

PMID- 19404909
TI  - [Connection between hyponatriemia and local herpes in an old lady?].
AB  - We report the case of a 84 year old patient who developed a syndrome of
      inappropriate antidiuretic hormone secretion (SIADH) with severe hyponatremia in
      the context of a localized herpes zoster L1/2. This is a rare but known
      complication of localized varizella zoster infection. Under water restriction and
      salt administration the hyponatremia was corrected slowly. One month after
      hospital discharge the patient showed a normal sodium value without diet.

PMID- 19404913
TI  - [Tachycardias--CME-EKG 24. Solution].

PMID- 19404916
TI  - Circulating tumor cells in HER-2 positive metastatic breast cancer patients
      treated with trastuzumab and chemotherapy.
AB  - The detection of circulating tumor cells (CTCs) in peripheral blood may have
      important prognostic and predictive implications in breast cancer treatment. A
      limitation in this field has been the lack of a validated method of accurately
      measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains
      a major challenge. The goal of this paper is to present a sensitive and specific
      methodology of detecting CTCs in women with HER-2 positive metastatic breast
      cancer, and to examine its role as a marker that tracks disease response during
      treatment with trastuzumab-containing regimens. The study included patients with
      HER-2-positive metastatic breast cancer enrolled on two different clinical
      protocols using a trastuzumab-containing regimen. Serial CTCs were measured at
      planned time points and clinical correlations were made. Immunomagnetic selection
      of circulating epithelial cells was used to address the specificity of tumor cell
      detection using cytokeratin 19 (CK19). In addition, the extracellular domain of
      the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19
      accurately reflect tumor burden. The presence of CTCs at first restaging was
      associated with disease progression. We observed an association between CK19 and
      HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar
      pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall
      response and a change of HER-2/ECD from positive at baseline to negative at best
      overall response was associated with favorable treatment response. Our study
      supports the prognostic and predictive role of the detection of CTCs in treatment
      of HER-2-positive metastatic breast cancer patients. The association between CK19
      and markers of disease burden is in line with the concept that CTCs may be a
      reliable measure of tumor cells in the peripheral blood of patients with
      metastatic breast cancer. The association of CTCs at first restaging with
      treatment failure indicates that CTCs may have a role as surrogate markers to
      monitor treatment response.

PMID- 19404917
TI  - Association of interleukin-6 -174G>C promoter polymorphism with risk of cervical
      cancer.
AB  - BACKGROUND: The etiology of cervical cancer is associated with excessive
      inflammation-mediated tumorigenesis. Interleukin-6 (IL-6), a multifunctional
      cytokine, regulates inflammation and various physiological processes. We
      therefore aimed to evaluate the association of the IL-6 -174G>C polymorphism with
      predisposition to cervical cancer. MATERIALS AND METHODS: The present case
      control study comprised 160 histopathologically confirmed cases of cervical
      cancer and 200 healthy controls. Polymorphism for the IL-6 gene was genotyped by
      amplification refractory mutation system (ARMS) polymerase chain reaction (PCR).
      RESULTS: We observed a significant association of the IL-6 -174CC genotype with
      risk of cervical cancer (OR=3.16; p=0.014). An increased risk of developing stage
      I tumors was found in individuals with a heterozygous (GC) genotype (OR=3.63,
      p=0.003). In a case-only analysis, the risk was further increased in patients
      consuming tobacco products (OR=3.14; p=0.033). CONCLUSION: The CC genotype in the
      IL-6 promoter region may confer a high risk of cervical cancer, which is further
      modulated in patients who are tobacco users.

PMID- 19404918
TI  - Mutational analysis of the BRAF gene in transitional cell carcinoma of the
      bladder.
AB  - PURPOSE: Mutational activation of the MAP kinase pathway is frequently found in
      many types of cancer. Recently, activating mutations in the BRAF gene, an
      important activator of this pathway, have been described in several tumor types
      including melanoma, colorectal and papillary thyroid cancer. The most frequent
      mutation in exon 15 (V600E) as well as several other mutations within exons 11
      and 15 result in constitutive activation of the oncoprotein. MATERIALS AND
      METHODS: Our study aimed to investigate BRAF mutations in 30 human bladder tumors
      and their adjacent normal tissues. The V600E mutation was screened by PCR/RFLP
      and exons 11, 14 and 15 of BRAF including intron-exon boundaries were sequenced.
      RESULTS: We detected two tumor specimens bearing two different mutations, both of
      which were found in exon 15. One sample showed the T1799A (V600E) and the other
      the G1798T (V600L) mutation. The first specimen was stage pT1a and grade II,
      whereas the second was stage pT2b and grade III. No mutations within the coding
      region of exons 11, 14, 15 and the intron-exon junctions for the remaining
      samples were found. CONCLUSIONS: Our results suggest that involvement of BRAF
      mutations in the development of transitional cell carcinoma of the bladder is
      infrequent.

PMID- 19404919
TI  - Quantification of VEGF isoforms and VEGFR transcripts by qRT-PCR and their
      significance in acute myeloid leukemia.
AB  - Vascular endothelial growth factor (VEGF) and its receptors are known to play an
      important role in normal and pathological hematopoiesis but the prognostic impact
      of VEGF isoform transcripts in acute myeloid leukemia (AML) has not been
      addressed. We conducted a single-institution prospective study to analyze the
      impact of these angiogenic factors and the expression of their receptors on the
      survival of adult patients newly diagnosed with AML. We investigated the levels
      of VEGF transcript isoforms VEGF121, -145, -165, -189 and -206 and their
      receptors, VEGFR-1 and VEGFR-2, using quantitative reverse transcriptase
      polymerase chain reaction assays in peripheral blood mononuclear cells (PBMCs) of
      67 consecutive AML patients at diagnosis. VEGF total protein was measured for
      comparison with mRNA levels in PBMCs. The VEGF121 splice variant transcript in
      AML PBMCs was significantly higher than in the normal controls. VEGF transcripts
      were quantified in all samples while its protein was detected in 42/67 (63%) of
      AML samples. High levels of VEGF121, VEGF165 transcripts and VEGF protein in AML
      were significantly related to a worse prognosis when analyzing overall survival
      (p<0.0001, p=0.019 and p=0.012, respectively) or event-free survival (p<0.0001,
      p=0.010 and p=0.047) using univariate analysis. In multivariable analysis only
      VEGF121 expression remained an independent prognostic factor for either event
      free survival or overall survival [aHR=8.83 (3.48-22.4), p<0.0001, and aHR=9.52
      (3.41-26.6), p<0.0001]. No prognostic value was observed for the other isoforms
      and the two receptors. Our findings show that the level of VEGF121 mRNA in
      circulating cells from AML patients is a strong independent prognostic parameter,
      which could be useful in the management of unselected AML patients.

PMID- 19404920
TI  - Haptoglobin genotypes in nasopharyngeal carcinoma.
AB  - AIM: Haptoglobin polymorphisms are associated with different cancers; however,
      the occurrence of nasopharyngeal carcinoma (NPC) in relation to haptoglobin
      polymorphisms has not been reported. In this study, the distribution of
      haptoglobin genotypes among patients with NPC was investigated and the prognostic
      significance of haptoglobin genotypes was further analyzed. MATERIAL AND METHODS:
      Haptoglobin genotypes were analyzed using polymerase chain reaction and
      electrophoresis. The genotypes were determined in the sera of 49 NPC patients and
      in 134 controls. RESULTS: The haptoglobin genotypes of patients with NPC were as
      follows: Hp 1-1, 2%; Hp 2-1, 39%; Hp 2-2, 59%. The frequency of the Hp 2-2
      genotype was much higher in NPC patients than in control individuals (p=0.044).
      Furthermore, NPC patients with the Hp 2-2 genotype had advanced T stages
      (p=0.001) and larger primary tumor volumes (p=0.035) than those with Hp 2-1 or 1
      1. CONCLUSION: An increased frequency of the Hp 2-2 genotype was associated with
      NPC. The Hp 2 allele was also overexpressed in NPC patients. NPC patients with
      the Hp 2-2 genotype had advanced T stage and a larger primary tumor volume. Hp 2
      2 may be a negative prognostic factor in NPC.

PMID- 19404921
TI  - Cytokeratin and vimentin expression in breast cancer.
AB  - BACKGROUND: The transition from epithelial keratin to mesenchymal vimentin
      expression marks an important step in the malignant progression of breast cancer.
      This study analyzed the clinical significance of cytokeratin and vimentin in
      patients with breast cancer. MATERIALS AND METHODS: Expression of cytokeratin and
      vimentin was evaluated by immunohistochemistry on paraffin-embedded tissue
      sections of patients with breast cancer. RESULTS: Loss of cytokeratin was seen in
      11% of the patients. A clearer trend towards loss of cytokeratin was observed in
      patients with stage IV disease and PR negativity. Weak cytokeratin expression was
      present in patients who developed recurrence or metastatic disease. Loss of
      cytokeratin was associated with reduced overall survival in univariate and
      multivariate analysis, gain of vimentin expression was seen in 57% of breast
      carcinoma patients. It was higher in patients with lymph node positivity,
      advanced stage, HER2 positivity, and disease recurrence or metastasis.
      Multivariate survival analysis indicated that gain of vimentin expression was
      associated with reduced relapse-free survival. CONCLUSION: Loss of cytokeratin
      and gain of vimentin expression are indicators of biologically aggressive breast
      carcinoma.

PMID- 19404923
TI  - Elevated CA 19-9 levels in mature cystic teratoma of the ovary.
AB  - The purpose of this study was to evaluate the clinical value of serum tumor
      markers in patients with ovarian mature cystic teratoma (MCT). We retrospectively
      evaluated 163 women who underwent surgery for MCT of the ovary between March 2003
      and August 2007 and who provided preoperative blood samples for the measurement
      of CA 19-9 and CA 125. The rates of elevated serum CA 19-9 and CA 125 levels were
      31.9% (52/163) and 13.5% (22/163), respectively. The rate of ovarian torsion was
      12.9% (21/163). There were significant differences between the elevated CA 19-9
      group and the normal CA 19-9 group in the diameters of the tumors and the rates
      of ovarian torsion. Elevated serum CA 19-9 levels correlated with larger tumor
      diameters and higher torsion rates. CA 19-9 may be a useful tool for the
      diagnosis of ovarian MCT. Elevated CA 19-9 levels appear to correlate with larger
      tumor diameters and higher rates of ovarian torsion.

PMID- 19404922
TI  - Levels of cathepsins S and H in pleural fluids of inflammatory and neoplastic
      origin.
AB  - Cathepsins S and H are present in immune cells and tissues and may play a role in
      the activation of an adoptive immune response. Our goal was to assess their
      protein levels in pleural fluids from 82 patients who underwent thoracentesis or
      thoracoscopy for therapeutic or diagnostic reasons and to relate them to an
      inflammatory, neoplastic or hemodynamic origin. Pleural effusions were also
      analyzed for a panel of 13 inflammatory or proliferative markers to test possible
      links to a nonspecific host reaction. Increased levels of cathepsin S were found
      in parainflammatory and cancer-related effusions compared to transudates.
      Cathepsin H levels were elevated only in parainflammatory effusions, whereas the
      levels in cancer-related effusions were comparable to transudates. Cathepsin S
      values significantly correlated with LDH, alpha-1-AT, VEGF, sICAM, sVCAM, MPO,
      uPA, MMP-9/TIMP-1, IL-8 and MCP-1, but not with CRP, IL-10 or cathepsin H. In
      contrast to cathepsin S, cathepsin H values did not correlate with markers of
      inflammation, indicating a specific role for cathepsin H in the pleural host
      response. In conclusion, the estimation of cathepsin S and cathepsin H may help
      to distinguish between effusions of different etiology.

PMID- 19404925
TI  - The effect of newer drugs on health spending: do they really increase the costs?
AB  - We analyze the influence of technological progress on pharmaceuticals on rising
      health expenditures using US State level panel data. Improvements in medical
      technology are believed to be partly responsible for rapidly rising health
      expenditures. Even if the technological progress in medicine improves health
      outcomes and life quality, it can also increase the expenditure on health care.
      Our findings suggest that newer drugs increase the spending on prescription drugs
      since they are usually more expensive than their predecessors. However, they
      lower the demand for other types of medical services, which causes the total
      spending to decline. We estimate that a 1-year decrease in the average age of
      prescribed drugs causes per capita health expenditures to decrease by $45.43. The
      biggest decline occurs in spending on hospital care due to newer drugs.

PMID- 19404924
TI  - Gene-specific methylation: potential markers for colorectal cancer.
AB  - PURPOSE: Aberrant methylation of the promoter region is associated with silencing
      of many genes in neoplasia. CpG island methylation is an epigenetic mechanism for
      transcriptional silencing that occurs at various stages of colon tumorigenesis.
      In this study, we tested the promoter methylation and expression of seven genes
      from various pathways of DNA repair, apoptosis and inflammation, i.e., sFRP1,
      MLH1, RASSF1A, CDA, v-fgr, LYN-B, and TNFR10d. METHOD: The genes were analyzed by
      quantitative polymerase chain reaction for the level of gene expression. The
      promoter methylation status of the genes was studied by methylation-specific
      polymerase chain reaction. RESULT: The correlation of promoter methylation status
      with suppressed gene expression patterns suggested a potential role for the
      silencing these genes in colon cancer progression. CONCLUSION: Promoter
      methylations of the studied genes could be explored as promising biomarkers for
      new diagnostic, prognostic and therapeutic targets of colorectal cancer.

PMID- 19404926
TI  - LC/MS/MS analysis of capsaicin using multiple transition pairs-some view points
      to ponder.

PMID- 19404927
TI  - On-column refolding of corticotropin-releasing factor receptor 1 extracellular
      domain by size exclusion chromatography.
AB  - Expressing the extracellular domain of corticotropin releasing factor receptor 1
      in Escherichia coli usually results in the formation of inclusion bodies. Here we
      describe the optimization of refolding by applying size exclusion chromatography
      with a denaturing guanidine hydrochloride gradient and a refolding buffer
      containing glycerol. Several chromatographic parameters like gradient length,
      flow rate, sample concentration and chromatography resin characteristics were
      evaluated. Recovery yields of refolded protein above 50% using a Superdex 200
      column demonstrate the usefulness of this method.

PMID- 19404928
TI  - Tocilizumab and missed personalized medicine opportunities for patients with
      rheumatoid arthritis?

PMID- 19404929
TI  - MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant
      protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To elucidate the role of microRNA (miRNA) in the pathogenesis of
      rheumatoid arthritis (RA), we analyzed synoviocytes from RA patients for their
      miRNA expression. METHODS: Synoviocytes derived from surgical specimens obtained
      from RA patients were compared with those obtained from osteoarthritis (OA)
      patients for their expression of a panel of 156 miRNA with quantitative stem-loop
      reverse transcription-polymerase chain reaction. The miRNA whose expression
      decreased or increased in RA synoviocytes as compared with OA synoviocytes were
      identified, and their target genes were predicted by computer analysis. We used
      an in vitro system of enhancing the expression of specific miRNA by transfection
      of precursors into synoviocytes, and then we performed proliferation, cell cycle,
      and apoptosis assays, as well as enzyme-linked immunosorbent assays for cytokine
      production. The effects of transfection on predicted target protein and messenger
      RNA (mRNA) were then examined by Western blot analysis and luciferase reporter
      assay. RESULTS: We found that miR-124a levels significantly decreased in RA
      synoviocytes as compared with OA synoviocytes. Transfection of precursor miR-124a
      into RA synoviocytes significantly suppressed their proliferation and arrested
      the cell cycle at the G1 phase. We identified a putative consensus site for miR
      124a binding in the 3'-untranslated region of cyclin-dependent kinase 2 (CDK-2)
      and monocyte chemoattractant protein 1 (MCP-1) mRNA. Induction of miR-124a in RA
      synoviocytes significantly suppressed the production of the CDK-2 and MCP-1
      proteins. Luciferase reporter assay demonstrated that miR-124a specifically
      suppressed the reporter activity driven by the 3'-untranslated regions of CDK-2
      and MCP-1 mRNA. CONCLUSION: The results of this study suggest that miR-124a is a
      key miRNA in the posttranscriptional regulatory mechanisms of RA synoviocytes.

PMID- 19404931
TI  - Clinical images: Oxalate tophus.

PMID- 19404932
TI  - The sense of smell in systemic lupus erythematosus.
AB  - OBJECTIVE: To assess the olfactory functions in systemic lupus erythematosus
      (SLE) patients compared with age- and sex-matched healthy controls, and to
      examine the association between the sense of smell and disease activity and
      central nervous system (CNS) involvement. METHODS: Olfactory functions in 50 SLE
      patients and 50 age- and sex-matched controls were evaluated using the Sniffin'
      Sticks test, the 3 stages of which are threshold, discrimination, and
      identification (TDI) of different odors. TDI scores were analyzed according to
      SLE disease activity and CNS involvement. RESULTS: In both the SLE and control
      groups, smell deficit correlated with male sex and older age. A decrease in the
      sense of smell was observed in SLE patients (46%) and controls (25%) (P<or=0.02),
      while loss of smell (anosmia) was documented only in SLE patients (10%). Total
      TDI scores and individual stages of smell correlated with SLE Disease Activity
      Index (P<0.001) and CNS manifestations (P<0.03). CONCLUSION: Our findings suggest
      that there is a decrease in the sense of smell in SLE patients compared with
      healthy subjects and that the decrease in the sense of smell among SLE patients
      correlates with disease activity and CNS involvement.

PMID- 19404930
TI  - Altered mineralization of human osteoarthritic osteoblasts is attributable to
      abnormal type I collagen production.
AB  - OBJECTIVE: Bone tissue in osteoarthritis (OA) is composed of abundant
      undermineralized osteoid matrix. The aim of this study was to investigate the
      mechanisms responsible for this abnormal matrix, using in vitro OA subchondral
      osteoblasts. METHODS: Primary normal and OA osteoblasts were prepared from tibial
      plateaus. Phenotype was determined by alkaline phosphatase activity, and
      osteocalcin, osteopontin, prostaglandin E2 (PGE2), and transforming growth factor
      beta1 (TGFbeta1) were assessed by enzyme-linked immunosorbent assay. Expression
      of COL1A1 and COL1A2 was determined by real-time polymerase chain reaction. The
      production of type I collagen was determined by the release of its C-terminal
      propeptide and Western blot analysis. In vitro mineralization was evaluated by
      alizarin red staining. Inhibition of TGFbeta1 expression was performed using a
      small interfering RNA technique. RESULTS: Mineralization of OA osteoblasts was
      reduced compared with mineralization of normal osteoblasts, even in the presence
      of bone morphogenetic protein 2 (BMP-2). Alkaline phosphatase and osteocalcin
      levels were elevated in OA osteoblasts compared with normal osteoblasts, whereas
      osteopontin levels were similar. The COL1A1-to-COL1A2 messenger RNA ratio was 3
      fold higher in OA osteoblasts compared with normal osteoblasts, and the
      production of collagen by OA osteoblasts was increased. Because TGFbeta1 inhibits
      BMP-2-dependent mineralization, and because TGFbeta1 levels are approximately 4
      fold higher in OA osteoblasts than in normal osteoblasts, inhibiting TGFbeta1
      levels in OA osteoblasts corrected the abnormal COL1A1-to-COL1A2 ratio and
      increased alizarin red staining. CONCLUSION: Elevated TGFbeta1 levels in OA
      osteoblasts are responsible, in part, for the abnormal ratio of COL1A1 to COL1A2
      and for the abnormal production of mature type I collagen. This abnormal COL1A1
      to-COL1A2 ratio generates a matrix that blunts mineralization in OA osteoblasts.

PMID- 19404933
TI  - Improvement of lipid profile is accompanied by atheroprotective alterations in
      high-density lipoprotein composition upon tumor necrosis factor blockade: a
      prospective cohort study in ankylosing spondylitis.
AB  - OBJECTIVE: Cardiovascular mortality is increased in ankylosing spondylitis (AS),
      and inflammation plays an important role. Inflammation deteriorates the lipid
      profile and alters high-density lipoprotein cholesterol (HDL-c) composition,
      reflected by increased concentrations of serum amyloid A (SAA) within the
      particle. Anti-tumor necrosis factor (anti-TNF) treatment may improve these
      parameters. We therefore undertook the present study to investigate the effects
      of etanercept on lipid profile and HDL composition in AS. METHODS: In 92 AS
      patients, lipid levels and their association with the inflammation markers C
      reactive protein (CRP), erythrocyte sedimentation rate, and SAA were evaluated
      serially during 3 months of etanercept treatment. HDL composition and its
      relationship to inflammation markers was determined in a subgroup of patients,
      using surface-enhanced laser desorption/ionization time-of-flight analysis.
      RESULTS: With anti-TNF treatment, levels of all parameters of inflammation
      decreased significantly, whereas total cholesterol, HDL-c, and apolipoprotein A-I
      (Apo A-I) levels increased significantly. This resulted in a better total
      cholesterol:HDL-c ratio (from 3.9 to 3.7) (although the difference was not
      statistically significant), and an improved Apo B:Apo A-I ratio, which decreased
      by 7.5% over time (P=0.008). In general, increases in levels of all lipid
      parameters were associated with reductions in inflammatory activity. In addition,
      SAA was present at high levels within HDL particles from AS patients with
      increased CRP levels and disappeared during treatment, in parallel with declining
      plasma levels of SAA. CONCLUSION: Our results show for the first time that during
      anti-TNF therapy for AS, along with favorable changes in the lipid profile, HDL
      composition is actually altered whereby SAA disappears from the HDL particle,
      increasing its atheroprotective ability. These findings demonstrate the
      importance of understanding the role of functional characteristics of HDL-c in
      cardiovascular diseases related to chronic inflammatory conditions.

PMID- 19404934
TI  - Evaluation of the diagnostic utility of spinal magnetic resonance imaging in
      axial spondylarthritis.
AB  - OBJECTIVE: Magnetic resonance imaging (MRI) is increasingly used for the
      diagnosis of axial spondylarthritis (SpA), but it is unknown whether
      characteristic lesions are actually specific for SpA. This study was undertaken
      to compare MRI patterns of disease in active SpA, degenerative arthritis (DA),
      and malignancy. METHODS: Fat-suppressed MRI of the axial skeleton was performed
      on 174 patients with back pain and 11 control subjects. Lesions detected by MRI,
      including Romanus lesions (RLs) and end-plate, diffuse vertebral body, posterior
      element, and spinous process bone marrow edema (BME) lesions, were scored in a
      blinded manner. An imaging diagnosis was given based on MRI findings alone, and
      this was compared with the gold-standard treating physician's diagnosis. RESULTS:
      The physician diagnosis was SpA in 64 subjects, DA in 45 subjects, malignancy in
      45 subjects, other diagnoses in 20 subjects, and normal in 11 subjects. There was
      72% agreement between the imaging diagnosis and physician diagnosis. End-plate
      edema, degenerative discs, and RLs were frequently observed in patients with any
      of the 3 major diagnoses. Single RLs were of low diagnostic utility for SpA, but
      >or=3 RLs (likelihood ratio [LR] 12.4) and severe RLs (LR infinite) in younger
      subjects were highly diagnostic of SpA. Posterior element BME lesions of mild or
      moderate grade were also highly diagnostic of SpA (LR 14.5). The most common
      diagnostic confusion was between SpA and DA, since both had RLs present and the
      presence/absence of degenerative discs did not change the diagnostic assessment.
      CONCLUSION: This study confirms the high diagnostic utility of MRI in axial SpA,
      with severe or multiple RLs evident on MRI being characteristic in younger
      patients and mild/moderate posterior element lesions being specific for SpA.
      However, MRI lesions previously considered to be characteristic of SpA could also
      be found frequently in patients with DA and patients with malignancy, and
      therefore such lesions should be interpreted with caution, particularly in older
      patients.

PMID- 19404935
TI  - Histone deacetylase 7, a potential target for the antifibrotic treatment of
      systemic sclerosis.
AB  - OBJECTIVE: We have recently shown a significant reduction in cytokine-induced
      transcription of type I collagen and fibronectin in systemic sclerosis (SSc) skin
      fibroblasts upon treatment with trichostatin A (TSA). Moreover, in a mouse model
      of fibrosis, TSA prevented the dermal accumulation of extracellular matrix. The
      purpose of this study was to analyze the silencing of histone deacetylase 7 (HDAC
      7) as a possible mechanism by which TSA exerts its antifibrotic function.
      METHODS: Skin fibroblasts from patients with SSc were treated with TSA and/or
      transforming growth factor beta. Expression of HDACs 1-11, extracellular matrix
      proteins, connective tissue growth factor (CTGF), and intercellular adhesion
      molecule 1 (ICAM-1) was analyzed by real-time polymerase chain reaction, Western
      blotting, and the Sircol collagen assay. HDAC-7 was silenced using small
      interfering RNA. RESULTS: SSc fibroblasts did not show a specific pattern of
      expression of HDACs. TSA significantly inhibited the expression of HDAC-7,
      whereas HDAC-3 was up-regulated. Silencing of HDAC-7 decreased the constitutive
      and cytokine-induced production of type I and type III collagen, but not
      fibronectin, as TSA had done. Most interestingly, TSA induced the expression of
      CTGF and ICAM-1, while silencing of HDAC-7 had no effect on their expression.
      CONCLUSION: Silencing of HDAC-7 appears to be not only as effective as TSA, but
      also a more specific target for the treatment of SSc, because it does not up
      regulate the expression of profibrotic molecules such as ICAM-1 and CTGF. This
      observation may lead to the development of more specific and less toxic targeted
      therapies for SSc.

PMID- 19404936
TI  - The alpha7 nicotinic acetylcholine receptor on fibroblast-like synoviocytes and
      in synovial tissue from rheumatoid arthritis patients: a possible role for a key
      neurotransmitter in synovial inflammation.
AB  - OBJECTIVE: Recent studies have suggested an important role for neurotransmitters
      as modulators of inflammation. Therefore, we undertook this study to investigate
      the expression of the alpha7 subunit of the nicotinic acetylcholine receptor
      (alpha7nAChR) and its function in rheumatoid arthritis (RA). METHODS: The
      potential role of the alpha7nAChR in modulating proinflammatory cytokine
      expression in fibroblast-like synoviocytes (FLS) was identified by screening an
      adenoviral short hairpin RNA (Ad.shRNA) library. An alpha7-specific antibody was
      used for immunohistochemistry, and fluorescein isothiocyanate-labeled alpha
      bungarotoxin, which binds specifically to the alpha7nAChR, was used for
      immunofluorescence. Gene expression in FLS was determined by quantitative
      polymerase chain reaction with primers specific for the alpha7nAChR. In addition,
      we analyzed messenger RNA (mRNA) expression of dupalpha7, a variant alpha7
      transcript. Next, we studied the functional role of the alpha7nAChR in RA FLS by
      examining the effects of alpha7-specific agonists on the production of
      interleukin-6 (IL-6) and IL-8 by activated FLS. RESULTS: A screen using an
      Ad.shRNA library against 807 transcripts revealed that a specific alpha7nAChR
      shRNA potently modulated IL-8 and matrix metalloproteinase expression in FLS. The
      alpha7nAChR was expressed in the inflamed synovium from RA patients,
      predominantly in the intimal lining layer. We found alpha7nAChR expression at
      both the mRNA and protein level in cultured RA FLS. FLS also constitutively
      expressed dupalpha7 mRNA. Specific alpha7nAChR agonists reduced tumor necrosis
      factor alpha-induced IL-6 and IL-8 production by FLS. CONCLUSION: The alpha7nAChR
      and its dupalpha7 variant are expressed in RA synovium, where they may play a
      critical role in regulating inflammation. Targeting the alpha7nAChR could provide
      a novel antiinflammatory approach to the treatment of RA.

PMID- 19404938
TI  - Rheumatoid arthritis joint progression in sustained remission is determined by
      disease activity levels preceding the period of radiographic assessment.
AB  - OBJECTIVE: Joint damage is related to disease activity in rheumatoid arthritis
      (RA), but the degree of its progression and the temporal associations between
      disease activity and joint damage are unclear. The aim of this study was to
      evaluate whether there is a latency in the effect of disease activity on
      radiographic progression in patients with RA. METHODS: Data were obtained from
      the PREMIER trial, a 2-year randomized, controlled clinical trial of adalimumab
      plus methotrexate versus methotrexate alone or adalimumab alone in early RA.
      Radiographic progression of joint damage was calculated using the modified total
      Sharp score in a subset of patients whose disease was in remission (Simplified
      Disease Activity Index<or=3.3) in the second year of the trial. The progression
      of damage in the second year was compared between groups of patients whose
      disease was already in remission for an additional period of 3, 6, or 9 months
      during the first year. Analysis of variance was used to test for a linear trend.
      RESULTS: Among 794 patients with early RA, 119 (15%) achieved sustained remission
      during the second year, with no difference in radiographic progression across the
      3 treatment groups. Radiographic progression in the second year was significantly
      different between patients with 3, 6, or 9 additional months of remission during
      year 1 (mean change in the modified Sharp score 1.19 in those with 3 additional
      months of remission versus 0.20 in those with 6 additional months of remission
      and -0.32 in those with 9 additional months of remission; P<0.05). The results
      were supported by similar findings in a series of sensitivity analyses.
      CONCLUSION: These data indicate that the level of disease activity as well as the
      duration of remission affect subsequent progression of radiographic damage in RA.
      This latency between disease activity and its effects on radiographic progression
      should be considered when evaluating radiographic outcomes in trials of RA.

PMID- 19404937
TI  - Association of biomarkers with pre-radiographically defined and radiographically
      defined knee osteoarthritis in a population-based study.
AB  - OBJECTIVE: To evaluate 10 biomarkers in magnetic resonance imaging (MRI)
      determined, pre-radiographically defined osteoarthritis (pre-ROA) and
      radiographically defined OA (ROA) in a population-based cohort of subjects with
      symptomatic knee pain. METHODS: Two hundred one white subjects with knee pain,
      ages 40-79 years, were classified into OA subgroups according to MRI-based
      cartilage (MRC) scores (range 0-4) and Kellgren/Lawrence (K/L) grades of
      radiographic severity (range 0-4): no OA (MRC score 0, K/L grade<2), pre-ROA (MRC
      score>or=1, K/L grade<2), or ROA (MRC score>or=1, K/L grade>or=2). Urine and
      serum samples were assessed for levels of the following biomarkers: urinary
      biomarkers C-telopeptide of type II collagen (uCTX-II), type II and types I and
      II collagen cleavage neoepitopes (uC2C and uC1,2C, respectively), and N
      telopeptide of type I collagen, and serum biomarkers sC1,2C, sC2C, C-propeptide
      of type II procollagen (sCPII), chondroitin sulfate 846 epitope, cartilage
      oligomeric matrix protein, and hyaluronic acid. Multicategory logistic regression
      was performed to evaluate the association of OA subgroup with individual
      biomarker levels and biomarker ratios, adjusted for age, sex, and body mass
      index. RESULTS: The risk of ROA versus no OA increased with increasing levels of
      uCTX-II (odds ratio [OR] 3.12, 95% confidence interval [95% CI] 1.35-7.21), uC2C
      (OR 2.13, 95% CI 1.04-4.37), and uC1,2C (OR 2.07, 95% CI 1.06-4.04), and was
      reduced in association with high levels of sCPII (OR 0.53, 95% CI 0.30-0.94). The
      risk of pre-ROA versus no OA increased with increasing levels of uC2C (OR 2.06,
      95% CI 1.05-4.01) and uC1,2C (OR 2.06, 95% CI 1.12-3.77). The ratios of type II
      collagen degradation markers to collagen synthesis markers were better than
      individual biomarkers at differentiating the OA subgroups, e.g., the ratio of
      [uCTX-II][uC1,2C] to sCPII was associated with a risk of ROA versus no OA of 3.47
      (95% CI 1.34-9.03) and a risk of pre-ROA versus no OA of 2.56 (95% CI 1.03-6.40).
      CONCLUSION: Different cartilage degradation markers are associated with pre-ROA
      than are associated with ROA, indicating that their use as diagnostic markers
      depends on the stage of OA. Biomarker ratios contrasting cartilage degradation
      with cartilage synthesis are better able to differentiate OA stages compared with
      levels of the individual markers.

PMID- 19404939
TI  - Induction of the expression of profibrotic cytokines and growth factors in normal
      human peripheral blood monocytes by gadolinium contrast agents.
AB  - OBJECTIVE: Nephrogenic systemic fibrosis (NSF) is a severe fibrosing disorder
      occurring in patients with renal insufficiency. The majority of patients with
      this disorder have documented exposure to magnetic resonance imaging contrast
      agents containing Gd. The purpose of this study was to examine the effects of
      gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd[DTPA-BMA];
      Omniscan) as compared with Gd-DTPA and GdCl3 on the expression and production of
      cytokines and growth factors by normal human peripheral blood monocytes in vitro
      and to examine whether conditioned media from Gd-exposed peripheral blood
      monocytes could induce a profibrotic phenotype in dermal fibroblasts. METHODS:
      Normal human peripheral blood monocytes isolated by Ficoll-Hypaque gradient
      centrifugation and plastic adherence were incubated with various concentrations
      of Gd[DTPA-BMA], Gd-DTPA, or GdCl3. Gene expression of interleukins 4, 6, and 13,
      interferon-gamma, tumor necrosis factor alpha, transforming growth factor beta,
      connective tissue growth factor, and vascular endothelial growth factor were
      assessed by real-time polymerase chain reaction (PCR) analysis. Production and
      secretion of cytokines and growth factors by Gd compound-exposed monocytes was
      quantified by enzyme-linked immunosorbent assay proteome multiplex arrays. The
      effects of conditioned media from the Gd compound-exposed monocytes on the
      phenotype of normal human dermal fibroblasts were examined by real-time PCR and
      Western blotting. RESULTS: The 3 Gd-containing compounds stimulated the
      expression and production of numerous cytokines and growth factors by normal
      human peripheral blood monocytes. Conditioned media from these cells induced a
      profibrotic phenotype in normal human dermal fibroblasts. CONCLUSION: The 3 Gd
      containing compounds studied induce potent cellular responses in normal human
      peripheral blood monocytes, which may participate in the development of tissue
      fibrosis in NSF.

PMID- 19404940
TI  - Methylation status of CpG islands in the promoter regions of signature genes
      during chondrogenesis of human synovium-derived mesenchymal stem cells.
AB  - OBJECTIVE: Human synovium-derived mesenchymal stem cells (MSCs) can efficiently
      differentiate into mature chondrocytes. It has been suggested that DNA
      methylation is one mechanism that regulates human chondrogenesis; however, the
      methylation status of genes related to chondrogenic differentiation is not known.
      The purpose of this study was to investigate the CpG methylation status in human
      synovium-derived MSCs during experimental chondrogenesis, with a view toward
      potential therapeutic use in osteoarthritis. METHODS: Human synovium-derived MSCs
      were subjected to chondrogenic pellet culture for 3 weeks. The methylation status
      of 12 regions in the promoters of 10 candidate genes (SOX9, RUNX2, CHM1, FGFR3,
      CHAD, MATN4, SOX4, GREM1, GPR39, and SDF1) was analyzed by bisulfite sequencing
      before and after differentiation. The expression levels of these genes were
      analyzed by real-time reverse transcription-polymerase chain reaction.
      Methylation status was also examined in human articular cartilage. RESULTS:
      Bisulfite sequencing analysis indicated that 10 of the 11 CpG-rich regions
      analyzed were hypomethylated in human progenitor cells before and after 3 weeks
      of pellet culture, regardless of the expression levels of the genes. The
      methylation status was consistently low in SOX9, RUNX2, CHM1, CHAD, and FGFR3
      following an increase in expression upon differentiation and was low in GREM1 and
      GPR39 following a decrease in expression upon chondrogenesis. One exceptional
      instance of a differentially methylated CpG-rich region was in a 1-kb upstream
      sequence of SDF1, the expression of which decreased upon differentiation.
      Paradoxically, the hypermethylation status of this region was reduced after 3
      weeks of pellet culture. CONCLUSION: The DNA methylation levels of CpG-rich
      promoters of genes related to chondrocyte phenotypes are largely kept low during
      chondrogenesis in human synovium-derived MSCs.

PMID- 19404941
TI  - Cartilage repair in a rat model of osteoarthritis through intraarticular
      transplantation of muscle-derived stem cells expressing bone morphogenetic
      protein 4 and soluble Flt-1.
AB  - OBJECTIVE: The control of angiogenesis during chondrogenic differentiation is an
      important issue affecting the use of stem cells in cartilage repair, especially
      with regard to the persistence of regenerated cartilage. This study was
      undertaken to investigate the effect of vascular endothelial growth factor (VEGF)
      stimulation and the blocking of VEGF with its antagonist, soluble Flt-1 (sFlt-1),
      on the chondrogenesis of skeletal muscle-derived stem cells (MDSCs) in a rat
      model of osteoarthritis (OA). METHODS: We investigated the effect of VEGF on
      cartilage repair in an immunodeficiency rat model of OA after intraarticular
      injection of murine MDSCs expressing bone morphogenetic protein 4 (BMP-4) in
      combination with MDSCs expressing VEGF or sFlt-1. RESULTS: In vivo, a combination
      of sFlt-1- and BMP-4-transduced MDSCs demonstrated better repair without
      osteophyte formation macroscopically and histologically following OA induction,
      when compared with the other groups. Higher differentiation/proliferation and
      lower levels of chondrocyte apoptosis were also observed in sFlt-1- and BMP-4
      transduced MDSCs compared with a combination of VEGF- and BMP-4-transduced MDSCs
      or with BMP-4-transduced MDSCs alone. In vitro experiments with mixed pellet
      coculture of MDSCs and OA chondrocytes revealed that BMP-4-transduced MDSCs
      produced the largest pellets, which had the highest gene expression of not only
      type II collagen and SOX9 but also type X collagen, suggesting formation of
      hypertrophic chondrocytes. CONCLUSION: Our results demonstrate that MDSC-based
      therapy involving sFlt-1 and BMP-4 repairs articular cartilage in OA mainly by
      having a beneficial effect on chondrogenesis by the donor and host cells as well
      as by preventing angiogenesis, which eventually prevents cartilage resorption,
      resulting in persistent cartilage regeneration and repair.

PMID- 19404942
TI  - Regulation of autophagy in human and murine cartilage: hypoxia-inducible factor 2
      suppresses chondrocyte autophagy.
AB  - OBJECTIVE: We have previously demonstrated that the transcription factor hypoxia
      inducible factor 1 (HIF-1) promotes the onset of autophagy in chondrocytes. The
      overall goal of this study was to test the hypothesis that another HIF family
      transcription factor, HIF-2, modulates the induction of autophagy by
      chondrocytes. METHODS: Expression of HIF-1, HIF-2, and light chain 3 (LC3) in
      human and murine articular cartilage was visualized by immunohistochemistry.
      Suppression of HIF-2 was achieved using small interfering RNA technology.
      Assessments of autophagic flux and lysosomal activity, as well as ultrastructural
      analysis, were performed in chondrocytes in cell culture. RESULTS: HIF-2 was
      expressed abundantly by cells in human and murine articular cartilage and in the
      cartilage of mineralizing vertebrae from neonatal mice. Protein levels were
      reduced in articular cartilage from older mice, in end-plate cartilage from mice,
      and in chondrocytes from human osteoarthritic (OA) cartilage. HIF-2 was robustly
      expressed in the prehypertrophic cells of mouse growth cartilage. When HIF-2alpha
      was silenced, the generation of reactive oxygen species was found to be elevated,
      with a concomitant decrease in catalase and superoxide dismutase activity.
      Suppression of HIF-2 was associated with decreased Akt-1 and mammalian target of
      rapamycin activities, reduced Bcl-xL expression, and a robust autophagic
      response, even under nutrient-replete conditions. In these silenced chondrocytes,
      HIF-1 expression was elevated. Decreased HIF-2 expression was associated with
      autophagy in OA tissues and aging cartilage samples. The autophagic response of
      chondrocytes in HIF-2alpha-knockout mouse growth plate showed an elevated
      autophagic response throughout the plate. CONCLUSION: Based on these
      observations, we conclude that HIF-2 is a potent regulator of autophagy in
      maturing chondrocytes. Our data suggest that this protein acts as a brake on the
      autophagy-accelerator function of HIF-1.

PMID- 19404943
TI  - Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL.
AB  - OBJECTIVE: RANKL has been implicated in the pathogenesis of glucocorticoid
      induced osteoporosis. This study was undertaken to evaluate the efficacy of
      denosumab, a neutralizing monoclonal antibody against human RANKL (hRANKL), in a
      murine model of glucocorticoid-induced osteoporosis. METHODS: Eight-month-old
      male homozygous hRANKL-knockin mice expressing a chimeric RANKL protein with a
      humanized exon 5 received 2.1 mg/kg of prednisolone or placebo daily over 4 weeks
      via subcutaneous slow-release pellets and were additionally treated with
      phosphate buffered saline or denosumab (10 mg/kg subcutaneously twice weekly).
      Two groups of wild-type mice were also treated with either prednisolone or
      vehicle. RESULTS: The 4-week prednisolone treatment induced loss of vertebral and
      femoral volumetric bone mineral density in the hRANKL-knockin mice.
      Glucocorticoid-induced bone loss was associated with suppressed vertebral bone
      formation and increased bone resorption, as evidenced by increases in the number
      of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, TRAP-5b
      protein in bone extracts, serum levels of TRAP-5b, and urinary excretion of
      deoxypyridinoline. Denosumab prevented prednisolone-induced bone loss by a
      pronounced antiresorptive effect. Biomechanical compression tests of lumbar
      vertebrae revealed a detrimental effect of prednisolone on bone strength that was
      prevented by denosumab. CONCLUSION: Our findings indicate that RANKL inhibition
      by denosumab prevents glucocorticoid-induced loss of bone mass and strength in
      hRANKL-knockin mice.

PMID- 19404944
TI  - Indoleamine 2,3 dioxygenase-mediated tryptophan catabolism regulates accumulation
      of Th1/Th17 cells in the joint in collagen-induced arthritis.
AB  - OBJECTIVE: Indoleamine 2,3 dioxygenase (IDO) is a catabolic enzyme that initiates
      the kynurenine pathway of tryptophan degradation and has immunomodulatory
      properties. The aim of this study was to investigate the regulation of collagen
      induced arthritis by tryptophan catabolism mediated by IDO. METHODS: Arthritis
      was induced by immunization with type II collagen. After induction of arthritis,
      the expression of IDO was analyzed by quantitative reverse transcription
      polymerase chain reaction. The effect of IDO deficiency on collagen-induced
      arthritis was assessed in vivo by administration of 1-methyltryptophan and
      clinical and histologic evaluation of IDO-deficient mice. The requirement for IDO
      activation was bypassed by administration of L-kynurenine. RESULTS: IDO was
      induced in lymph node dendritic cells after collagen immunization. Systemic
      inhibition of tryptophan catabolism during active arthritis increased disease
      severity. Conversely, bypassing the requirement for tryptophan degradation by the
      administration of L-kynurenine resulted in amelioration of arthritis.
      Furthermore, IDO-deficient mice showed a higher incidence of arthritis and
      exacerbated disease severity compared with IDO-competent mice. Such increased
      disease activity in IDO-deficient mice correlated early with increased production
      of the proinflammatory cytokines interferon-gamma and interleukin-17 by lymph
      node T cells and later with increased infiltration of Th1 and Th17 cells in the
      inflamed joints. CONCLUSION: Our data indicate that the induction of IDO controls
      the accumulation of Th1 and Th17 pathogenic T cells at the site of inflammation
      during collagen-induced arthritis. Therefore, manipulation of the kynurenine
      pathway of tryptophan degradation provides the potential for therapeutic
      intervention in rheumatoid arthritis.

PMID- 19404945
TI  - The good initial response to therapy with a combination of traditional disease
      modifying antirheumatic drugs is sustained over time: the eleven-year results of
      the Finnish rheumatoid arthritis combination therapy trial.
AB  - OBJECTIVE: To evaluate the evolution of functional and clinical outcomes over 11
      years in patients with early rheumatoid arthritis (RA) initially treated with a
      combination of 3 disease-modifying antirheumatic drugs (DMARDs) or with a single
      DMARD. METHODS: A cohort of 199 patients with early active RA were initially
      randomized to receive treatment with a combination of methotrexate,
      sulfasalazine, and hydroxychloroquine with prednisolone or treatment with a
      single DMARD (initially, sulfasalazine) with or without prednisolone. After 2
      years, the drug treatment strategy became unrestricted, but still targeted
      remission. At 11 years, function was assessed with the Health Assessment
      Questionnaire (HAQ), and clinical outcomes were assessed with the modified
      Minimal Disease Activity (MDA) measure and the American College of Rheumatology
      (ACR) criteria for remission. RESULTS: At 11 years, 138 patients were assessed
      (68 in the combination-DMARD group and 70 in the single-DMARD group). The mean+/
      SD HAQ scores were 0.34+/-0.54 in the combination-DMARD group and 0.38+/-0.58 in
      the single-DMARD group (P=0.88). Modified MDA was achieved by 63% (95% confidence
      interval [95% CI] 51, 77) and by 43% (95% CI 32, 55) (P=0.016) of the combination
      DMARD group and the single-DMARD group, respectively, and ACR remission by 37%
      (95% CI 26, 49) and by 19% (95% CI 11, 29) (P=0.017), respectively. CONCLUSION:
      Initial therapy with a combination of DMARDs in early RA results in higher rates
      of patients achieving modified MDA and strict ACR remission even over the long
      term than initial single-DMARD therapy. Targeting remission with tight clinical
      controls results in good functional and clinical outcomes in most RA patients.

PMID- 19404946
TI  - Induction of CCR2-dependent macrophage accumulation by oxidized phospholipids in
      the air-pouch model of inflammation.
AB  - OBJECTIVE: Macrophages are key players in the pathogenesis of rheumatoid
      synovitis as well as in atherosclerosis. To determine whether atherogenic
      oxidized phospholipids potentially contribute to synovial inflammation and
      subsequent monocyte/macrophage recruitment, we examined the effects of oxidized 1
      palmitoyl-2-arachidonoyl-sn-3-glycero-phosphorylcholine (OxPAPC) on chemokine
      expression and leukocyte recruitment in a facsimile synovium in vivo using the
      murine air-pouch model. METHODS: Air pouches were raised by 2 injections of
      sterile air, and inflammation was induced by injecting either lipopolysaccharide
      (LPS) or OxPAPC into the pouch lumen. Inflammation was assessed by analysis of
      inflammatory gene expression using reverse transcription-polymerase chain
      reaction or immunohistochemical analysis, and leukocytes were quantified in the
      lavage fluid and in the pouch wall after staining with Giemsa or after enzymatic
      digestion followed by fluorescence-activated cell sorter analysis. RESULTS:
      Application of OxPAPC resulted in selective recruitment of monocyte/macrophages
      into the air-pouch wall, but not in the lumen. In contrast, LPS induced both
      monocyte and neutrophil accumulation in the pouch lumen as well as in the wall.
      LPS, but not OxPAPC, induced the expression of adhesion molecules E-selectin, P
      selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule
      1. OxPAPC increased the expression of the CCR2 ligands monocyte chemotactic
      protein 1 (MCP-1), MCP-3, and MCP-5, as well as RANTES and growth-related
      oncogene alpha (GROalpha), while it down-regulated the expression of CCR2 on
      macrophages. Moreover, oxidized phospholipid-induced macrophage accumulation was
      abrogated in CCR2-/- mice. CONCLUSION: These data demonstrate that oxidized
      phospholipids trigger a type of inflammatory response that leads to selective
      macrophage accumulation in vivo, a process relevant for the pathogenesis of
      chronic inflammatory rheumatic diseases.

PMID- 19404947
TI  - Activation of the interferon-gamma signaling pathway in systemic lupus
      erythematosus peripheral blood mononuclear cells.
AB  - OBJECTIVE: To investigate interferon-gamma (IFNgamma) signaling in peripheral
      blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus
      (SLE) by analyzing IFNgamma receptor (IFNgammaR) expression, STAT-1 expression
      and phosphorylation, and the regulation of IFNgamma-inducible genes. METHODS:
      Fluorocytometry was used to investigate expression of STAT-1, pSTAT-1, CD95, HLA
      DR, class I major histocompatibility complex (MHC), IFNgamma-inducible 10-kd
      protein (IP-10), monokine induced by IFNgamma (Mig), and IFNgammaR in PBMCs from
      SLE patients and healthy individuals. STAT-1 phosphorylation was determined by
      fluorocytometry and Western blotting after stimulation with IFNalpha or IFNgamma.
      Quantitative polymerase chain reaction was used to assess messenger RNA (mRNA)
      expression of the IFNgamma-inducible genes IP-10 and Mig shortly after
      preparation or after stimulation with IFNgamma in monocytes. RESULTS: STAT-1
      expression was increased in PBMCs from SLE patients and correlated significantly
      with disease activity and with the IFN-inducible expression of CD95 and HLA-DR.
      STAT-1 expression also showed a trend toward association with class I MHC
      expression. In addition, the expression of other IFNgamma-inducible genes, such
      as IP-10 or Mig, was increased in SLE monocytes. While STAT-1 phosphorylation in
      SLE PBMCs and PBMCs from healthy individuals was similar after IFNalpha
      stimulation, incubation with IFNgamma induced STAT-1 phosphorylation only in SLE
      lymphocytes. Moreover, SLE monocytes showed a considerably higher increase in
      pSTAT-1 expression upon IFNgamma stimulation than monocytes from healthy
      individuals. Increased responsiveness of SLE monocytes to IFNgamma was also
      confirmed on the mRNA level, where expression of the IFN-inducible, STAT-1
      dependent genes IP-10 and Mig was more efficiently increased in SLE cells.
      However, IFNgammaR was similarly expressed on SLE lymphocytes and monocytes and
      those from healthy individuals. CONCLUSION: In addition to supporting the role of
      IFNs in SLE immunopathogenesis in general, the findings of the present study
      support a role of IFNgamma in this disease.

PMID- 19404949
TI  - Clinical images: Cement embolism following percutaneous vertebroplasty.

PMID- 19404948
TI  - Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritis.
AB  - OBJECTIVE: The majority of patients with Chlamydia-induced reactive arthritis do
      not present with the classic triad of arthritis, conjunctivitis/iritis, and
      urethritis. Moreover, acute chlamydial infections are often asymptomatic. The aim
      of the present study was to assess the prevalence of synovial Chlamydia
      trachomatis and Chlamydia pneumoniae infections in patients with chronic
      undifferentiated spondylarthritis (uSpA). METHODS: Study patients met the
      European Spondylarthropathy Study Group criteria for SpA, without evidence of
      ankylosing spondylitis, psoriasis, inflammatory bowel disease, or preceding
      dysentery. Symptoms were present for >or=6 months. Each patient underwent a
      synovial biopsy; tissue and concomitantly obtained peripheral blood mononuclear
      cells (PBMCs) were analyzed by polymerase chain reaction (PCR) for C trachomatis
      and C pneumoniae DNA. Other data collected on the day of the biopsy included
      standard demographic information and medical history, including any known history
      of C trachomatis or C pneumoniae. Physical examination (including joint count,
      evaluation for dactylitis and/or enthesitis, and skin examination) and HLA-B27
      typing were performed. Synovial tissue (ST) samples from 167 patients with
      osteoarthritis (OA) were used as controls. RESULTS: Twenty-six patients met the
      entry criteria and underwent synovial biopsy (25 knee, 1 wrist). Sixteen of them
      (62%) were positive for C trachomatis and/or C pneumoniae DNA (10 for C
      trachomatis, 4 for C pneumoniae, and 2 for both). PCR analysis of ST revealed the
      presence of Chlamydia significantly more frequently in patients with uSpA than in
      OA controls (P<0.0001). No specific clinical characteristics differentiated
      Chlamydia-positive from Chlamydia-negative patients. PBMCs from 4 of the 26 uSpA
      patients (15%) were positive for Chlamydia, and Chlamydia was found in ST from 2
      of these 4 patients. No significant correlation between PCR positivity and HLA
      B27 positivity was found. CONCLUSION: The frequency of Chlamydia-positive ST
      samples, as determined by PCR, was found to be significantly higher in patients
      with uSpA than in patients with OA. Our results suggest that in many patients
      with uSpA, chlamydial infection, which is often occult, may be the cause.

PMID- 19404950
TI  - Association of interleukin-1 receptor antagonist and interleukin-6 polymorphisms
      with osteolysis after total hip arthroplasty: comment on the article by Gordon et
      al.

PMID- 19404951
TI  - Association of a specific ERAP1/ARTS1 haplotype with disease susceptibility in
      ankylosing spondylitis.
AB  - OBJECTIVE: Alterations in antigen processing have been proposed to play a
      significant role in the pathogenesis of ankylosing spondylitis (AS). A non-major
      histocompatibility complex gene encoding an endoplasmic reticulum aminopeptidase,
      ERAP1, has been implicated recently. This study assessed 13 coding single
      nucleotide polymorphisms (SNPs) from 5 genes involved in antigen processing
      (ERAP1, TAP1, TAP2, LMP2, and LMP7) in 3 Canadian cohorts of patients with AS, to
      address the possibility of gene interactions in disease susceptibility. METHODS:
      The study involved 992 AS cases and 1,437 controls from 3 centers (472 cases and
      451 controls from Alberta, 138 cases and 392 controls from Newfoundland, and 382
      cases and 594 controls from Toronto). Most of the patients with AS and healthy,
      unrelated controls were Caucasians of northern European descent. Single-marker
      and haplotype associations were determined using an allelic likelihood ratio test
      in UNPHASED, version 3.0.12, and the WHAP program, respectively. P values for
      significance of haplotype associations were calculated using a permutation test.
      RESULTS: A specific ERAP1 haplotype, rs27044/10050860/30187-CCT, was strongly
      associated with increased risk of AS in all 3 case-control cohorts (pooled odds
      ratio [OR] 1.81, 95% confidence interval [95% CI] 1.46-2.24; P=7x10(-8)), while a
      second specific ERAP1 haplotype, rs30187/26618/26653-CTG, reduced the disease
      risk (pooled OR 0.77, 95% CI 0.67-0.88; P=9x10(-5)). Significant associations
      were also noted for 3 ERAP1 SNP variants (rs10050860, rs30187, and rs26653),
      although no significant haplotype interaction between ERAP1 and TAP/LMP loci was
      evident. CONCLUSION: These data indicate that an AS disease locus may reside on a
      specific ERAP1 haplotype, and its effect is not multiplicative with contributions
      from TAP and LMP genes.

PMID- 19404952
TI  - The PRL -1149 G/T polymorphism and rheumatoid arthritis susceptibility.
AB  - OBJECTIVE: Previous studies have demonstrated that the PRL -1149 T (minor) allele
      decreases prolactin expression and may be associated with autoimmune disease. The
      aim of this study was to determine the role of the PRL -1149 G/T polymorphism
      (rs1341239) in rheumatoid arthritis (RA) susceptibility. METHODS: We examined the
      association between PRL -1149 G/T and RA risk in 4 separate study populations,
      consisting of a total of 3,405 RA cases and 4,111 controls of self-reported white
      European ancestry. Samples were genotyped using 1 of 3 genotyping platforms, and
      strict quality control metrics were applied. We tested for association using a 2
      tailed Cochran-Mantel-Haenszel additive, fixed-effects model. RESULTS: In the
      individual populations, odds ratios (ORs) for an association between PRL -1149 T
      and RA risk ranged from 0.80 to 0.97. In a joint meta-analysis across all 4
      populations, the OR for an association between PRL -1149 T and RA risk was 0.90
      (95% confidence interval 0.84-0.96, P=0.001). CONCLUSION: Our findings indicate a
      possible association between the PRL -1149 T allele and decreased RA risk. The
      effect size is small but similar to ORs for other genetic polymorphisms
      associated with complex traits, including RA.

PMID- 19404955
TI  - Important role of interleukin-3 in the early phase of collagen-induced arthritis.
AB  - OBJECTIVE: Activation of basophils contributes to memory immune responses and
      results in exacerbation of collagen-induced arthritis (CIA). We undertook the
      present study to analyze the production and biologic effects of interleukin-3 (IL
      3), a strong activator of basophils, in CIA. METHODS: Arthritis was induced by
      immunization with type II collagen. Mice were treated with blocking monoclonal
      antibodies against IL-3 or with recombinant IL-3. Clinical scoring, histologic
      analysis, fluorescence-activated cell sorter analysis, enzyme-linked
      immunosorbent assay, and cell culturing were performed to assess disease activity
      and IL-3 production. RESULTS: IL-3 was produced in large quantities by collagen
      specific CD4+ T cells in the spleen and was present in the synovial tissue during
      onset of arthritis, but was down-regulated in paws with severe inflammation.
      Blockade of IL-3 during the time of arthritis onset resulted in profound
      improvement of the disease, with reductions in synovial leukocyte and cytokine
      levels, peripheral blood basophil levels, and anticollagen antibody titers.
      Blockade of IL-3 during the late phase of arthritis had no beneficial effect.
      Administration of recombinant IL-3 during onset of arthritis induced a marked
      exacerbation of the disease, with increased peripheral blood basophil and plasma
      IL-6 levels and increased titers of anticollagen antibody. In studies of the
      regulation of IL-3 expression in CD4+ T cells, IL-6 and IL-4 suppressed the
      release of IL-3 by activated CD4+ T cells, whereas lipopolysaccharide and CpG DNA
      up-regulated IL-3 secretion in activated CD4+ T cells by acting on costimulatory
      cells. CONCLUSION: Taken together, the present results demonstrate for the first
      time that IL-3 has an important role in the early phase of CIA.

PMID- 19404954
TI  - Regulation of pulmonary inflammation and fibrosis through expression of integrins
      alphaVbeta3 and alphaVbeta5 on pulmonary T lymphocytes.
AB  - OBJECTIVE: Pulmonary diseases associated with fibrosis, including scleroderma
      lung disease, are characterized by the accumulation of T cells in the lungs.
      These cells are thought to facilitate lung fibrosis, but the exact mechanisms of
      their profibrotic action are not clear. Several alphaV-containing integrins,
      including alphaVbeta3 and alphaVbeta5, have been shown to directly activate
      transforming growth factor beta (TGFbeta) and promote collagen accumulation. The
      aim of this study was to investigate whether pulmonary T cells express
      profibrotic integrins and regulate collagen accumulation. METHODS: Expression of
      integrins was assessed by immunohistochemical analysis of lung tissue, by flow
      cytometry using bronchoalveolar lavage fluid from patients with systemic
      sclerosis (SSc), and in a CCL18 overexpression animal model of pulmonary T cell
      infiltration. Experiments in cell cultures were performed to determine whether
      integrin-expressing T cells are profibrotic in cocultures with pulmonary
      fibroblasts and, if so, through what possible mechanism. RESULTS: Lymphocytes and
      integrin-positive cells were present in the lungs, and pulmonary T cells
      expressed integrins alphaVbeta3 and alphaVbeta5 in patients with SSc and in the
      animal model. Systemic administration of neutralizing anti-integrin alphaV
      antibody or a genetic deficiency of integrin beta3 in the CCL18 overexpression
      model significantly attenuated CCL18-driven pulmonary lymphocytic infiltration
      and collagen accumulation. Jurkat T cells overexpressing integrin alphaVbeta3 or
      integrin alphaVbeta5 in cocultures with primary pulmonary fibroblasts stimulated
      collagen accumulation and Smad2 nuclear translocation. Neutralizing anti-TGFbeta
      antibody attenuated the profibrotic effect of integrin-expressing T cells.
      CONCLUSION: Pulmonary infiltrating T lymphocytes may express integrins
      alphaVbeta3 and alphaVbeta5 that are necessary for lymphocytic infiltration and T
      cell-associated TGFbeta activation and collagen accumulation.

PMID- 19404956
TI  - Coexpression of CD177 and membrane proteinase 3 on neutrophils in antineutrophil
      cytoplasmic autoantibody-associated systemic vasculitis: anti-proteinase 3
      mediated neutrophil activation is independent of the role of CD177-expressing
      neutrophils.
AB  - OBJECTIVE: Wegener's granulomatosis (WG) is strongly associated with
      antineutrophil cytoplasmic autoantibodies (ANCAs) directed against proteinase 3
      (PR3). Recent studies have shown that membrane-bound PR3 (mPR3) is differentially
      expressed and colocalizes with CD177/NB1 on circulating neutrophils. We undertook
      this study to assess the differential expression of CD177 on neutrophils from
      patients with ANCA-associated systemic vasculitis (ASV) in comparison with
      patients with systemic lupus erythematosus (SLE), patients with rheumatoid
      arthritis (RA), and healthy individuals, and to investigate whether
      colocalization of mPR3 and CD177 affects anti-PR3-mediated neutrophil activation.
      METHODS: Expression of CD177 and mPR3 was analyzed by flow cytometry on isolated
      neutrophils from patients with ASV (n=53), those with SLE (n=30), those with RA
      (n=26), and healthy controls (n=31). Neutrophil activation mediated by anti-PR3
      antibodies was assessed by measuring the oxidative burst with a dihydrorhodamine
      assay. RESULTS: Percentages of CD177-expressing neutrophils were significantly
      higher in patients with ASV and those with SLE than in healthy controls. In 3
      healthy donors, CD177 expression was not detected. After priming with tumor
      necrosis factor alpha, neutrophils remained negative for CD177 while mPR3
      expression was induced. Neutrophils from CD177-negative donors or CD177-
      neutrophils sorted from donors with bimodal expression were susceptible to anti
      PR3-mediated oxidative burst. Variation in the extent of anti-PR3-mediated
      neutrophil activation among different donors occurred independent of the
      percentage of CD177-expressing neutrophils. CONCLUSION: Membrane expression of
      CD177 on circulating neutrophils is increased in patients with ASV and in those
      with SLE, but not in RA patients. However, primed neutrophils from CD177-negative
      individuals also express mPR3 and are susceptible to anti-PR3-mediated oxidative
      burst, suggesting that recruitment of CD177-independent mPR3 is involved in anti
      PR3-induced neutrophil activation.

PMID- 19404957
TI  - Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in
      rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled
      clinical studies.
AB  - OBJECTIVE: To assess the efficacy and safety of VX-702, a p38 MAPK inhibitor, in
      patients with active, moderate-to-severe rheumatoid arthritis (RA). METHODS: Two
      12-week, double-blind, placebo-controlled studies of VX-702 were conducted in
      patients with active, moderate-to-severe RA. In the VeRA study, 313 patients
      received placebo or 2 daily doses of VX-702. In Study 304, 117 patients received
      placebo, daily VX-702, or twice weekly VX-702 in addition to concomitant
      methotrexate (MTX). Study end points included the proportion of patients meeting
      the American College of Rheumatology 20% improvement criteria (an ACR20
      response), ACR50 and ACR70 responses, changes in the serum levels of biomarkers
      of inflammation, and safety assessments. RESULTS: The numerically superior ACR20
      response rates among patients receiving VX-702 compared with those receiving
      placebo in both studies did not reach pairwise statistical significance at the
      highest doses in either study. At week 12 in the VeRA study, ACR20 response rates
      were 40%, 36%, and 28% among patients receiving 10 mg of VX-702, 5 mg of VX-702,
      and placebo, respectively. In Study 304, the response rates were 40%, 44%, and
      22% for patients receiving 10 mg VX-702 daily plus MTX, 10 mg VX-702 twice weekly
      plus MTX, and placebo, respectively. Reductions in the levels of C-reactive
      protein, soluble tumor necrosis factor receptor p55, and serum amyloid A were
      observed as early as week 1 in both studies, but these levels rapidly returned to
      baseline values by week 4. The overall frequency of adverse events was similar
      between the VX-702 and placebo groups. In the VeRA study, serious infections were
      more frequent in the VX-702 groups compared with the placebo group (2.4% versus
      0%) but not in Study 304 (2.6% versus 4.9%). CONCLUSION: The modest clinical
      efficacy plus the transient suppression of biomarkers of inflammation observed in
      this study suggest that p38 MAPK inhibition may not provide meaningful, sustained
      suppression of the chronic inflammation seen in RA.

PMID- 19404958
TI  - Serum levels of vitamin D, sunlight exposure, and knee cartilage loss in older
      adults: the Tasmanian older adult cohort study.
AB  - OBJECTIVE: To determine the associations between serum levels of vitamin D,
      sunlight exposure, and knee cartilage loss cross-sectionally and longitudinally
      in older adults. METHODS: A total of 880 randomly selected subjects (mean age 61
      years [range 51-79 years], 50% women) were studied at baseline, and 353 of these
      subjects were studied 2.9 years later. Serum levels of 25-hydroxyvitamin D
      (25[OH]D) were assessed by radioimmunoassay, and sunlight exposure was assessed
      by questionnaire. T1-weighted fat-suppressed magnetic resonance imaging (MRI) of
      the right knee was performed to determine knee cartilage volume and defects. Knee
      radiographic osteoarthritis (OA) and knee pain were also assessed. RESULTS: The
      mean 25(OH)D serum level was 52.8 nmoles/liter at baseline (range 13-119
      nmoles/liter). Winter sunlight exposure and serum 25(OH)D level were both
      positively associated with medial and lateral tibial cartilage volume, and a
      serum 25(OH)D level<50 nmoles/liter was associated with increased medial
      tibiofemoral joint space narrowing (all P<0.05). Longitudinally, baseline serum
      25(OH)D level predicted change in both medial and lateral tibial cartilage volume
      (beta=+0.04% per annum per nmole/liter for both; P<0.05), and change in serum
      25(OH)D level was positively associated with change in medial tibial cartilage
      volume. These associations were consistent in subjects with radiographic OA and
      knee pain and/or in women, but not in men or in subjects without radiographic OA
      or knee pain. CONCLUSION: Sunlight exposure and serum 25(OH)D levels are both
      associated with decreased knee cartilage loss (assessed by radiograph or MRI).
      This is best observed using the whole range of 25(OH)D levels rather than
      predefined cut points and implies that achieving vitamin D sufficiency may
      prevent and/or retard cartilage loss in knee OA.

PMID- 19404959
TI  - Generalized Wegener's granulomatosis in an immunocompetent adult after
      cytomegalovirus mononucleosis and bacterial urinary tract infection.
AB  - Human cytomegalovirus (HCMV) is frequently detected in autoimmune diseases, but
      its role in such disorders is poorly understood. Herein we describe the case of a
      young woman who developed generalized Wegener's granulomatosis (WG) after HCMV
      mononucleosis and urinary tract infection. During mononucleosis, the patient had
      extraordinarily high plasma levels of proinflammatory cytokines such as
      interleukin-5 and lymphotoxin alpha, autoantibodies, and a higher blood level of
      viral DNA than were found in other immunocompetent patients infected with HCMV or
      healthy controls. Active HCMV replication was detected after the onset of
      vasculitis, and HCMV genomes or antigens were found in blood, urine, and
      inflammatory lesions on the kidney. Thus, HCMV may have triggered or exacerbated
      inflammation and autoimmunity in this case of WG.

PMID- 19404953
TI  - Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors
      for increased carotid intima-media thickness in the atherosclerosis prevention in
      pediatric lupus erythematosus cohort.
AB  - OBJECTIVE: To evaluate risk factors for subclinical atherosclerosis in a
      population of patients with pediatric systemic lupus erythematosus (SLE).
      METHODS: In a prospective multicenter study, a cohort of 221 patients underwent
      baseline measurements of carotid intima-media thickness (CIMT) as part of the
      Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial. SLE
      disease measures, medications, and traditional risk factors for atherosclerosis
      were assessed. A standardized protocol was used to assess the thickness of the
      bilateral common carotid arteries and the mean maximal IMT of 12 segments.
      Univariable analysis identified potential associations with CIMT, which were
      examined in multivariable linear regression modeling. RESULTS: Based on the mean
      mean common or the mean-max CIMT as the dependent variable, univariable analysis
      showed significant associations of the following variables with increased CIMT:
      increasing age, longer SLE duration, minority status, higher body mass index
      (BMI), male sex, increased creatinine clearance, higher lipoprotein(a) level,
      proteinuria, azathioprine treatment, and prednisone dose. In multivariable
      modeling, both azathioprine use (P=0.005 for the mean-mean model and P=0.102 for
      the mean-max model) and male sex (P<0.001) were associated with increases in the
      mean-max CIMT. A moderate dosage of prednisone (0.15-0.4 mg/kg/day) was
      associated with decreases in the mean-max CIMT (P=0.024), while high-dose and low
      dose prednisone were associated with increases in the mean-mean common CIMT
      (P=0.021) and the mean-max CIMT (P=0.064), respectively. BMI (P<0.001) and
      creatinine clearance (P=0.031) remained associated with increased mean-mean
      common CIMT, while increasing age (P<0.001) and increasing lipoprotein(a) level
      (P=0.005) were associated with increased mean-max CIMT. CONCLUSION: Traditional
      as well as nontraditional risk factors were associated with increased CIMT in
      this cohort of patients in the APPLE trial. Azathioprine treatment was associated
      with increased CIMT. The relationship between CIMT and prednisone dose may not be
      linear.

PMID- 19404960
TI  - Down-regulation of myeloid cell leukemia 1 by epigallocatechin-3-gallate
      sensitizes rheumatoid arthritis synovial fibroblasts to tumor necrosis factor
      alpha-induced apoptosis.
AB  - OBJECTIVE: Overexpression of the antiapoptotic protein myeloid cell leukemia 1
      (Mcl-1) in rheumatoid arthritis (RA) synovial fibroblasts is a major cause of
      their resistance to tumor necrosis factor alpha (TNFalpha)-induced apoptosis.
      This study was undertaken to evaluate the efficacy of epigallocatechin-3-gallate
      (EGCG) in down-regulating Mcl-1 expression and its mechanism of RA synovial
      fibroblast sensitization to TNFalpha-induced apoptosis. METHODS: EGCG effects on
      cultured RA synovial fibroblast cell morphology, proliferation, and viability
      over 72 hours were determined by microscopy and a fluorescent cell enumeration
      assay. Caspase 3 activity was determined by a colorimetric assay. Western
      blotting was used to evaluate the apoptosis mediators poly(ADP-ribose) polymerase
      (PARP), Mcl-1, Bcl-2, Akt, and nuclear translocation of NF-kappaB. RESULTS: In RA
      synovial fibroblasts, EGCG (5-50 microM) inhibited constitutive and TNFalpha
      induced Mcl-1 protein expression in a concentration- and time-dependent manner
      (P<0.05). Importantly, EGCG specifically abrogated Mcl-1 expression in RA
      synovial fibroblasts and affected Mcl-1 expression to a lesser extent in
      osteoarthritis and normal synovial fibroblasts or endothelial cells. Inhibition
      of Mcl-1 by EGCG triggered caspase 3 activity in RA synovial fibroblasts, which
      was mediated via down-regulation of the TNFalpha-induced Akt and NF-kappaB
      pathways. Caspase 3 activation by EGCG also suppressed RA synovial fibroblast
      growth, and this effect was mimicked by Akt and NF-kappaB inhibitors.
      Interestingly, Mcl-1 degradation by EGCG sensitized RA synovial fibroblasts to
      TNFalpha-induced PARP cleavage and apoptotic cell death. CONCLUSION: Our findings
      indicate that EGCG itself induces apoptosis and further sensitizes RA synovial
      fibroblasts to TNFalpha-induced apoptosis by specifically blocking Mcl-1
      expression and, hence, may be of promising adjunct therapeutic value in
      regulating the invasive growth of synovial fibroblasts in RA.

PMID- 19404962
TI  - Oncostatin M-induced CCL2 transcription in osteoblastic cells is mediated by
      multiple levels of STAT-1 and STAT-3 signaling: an implication for the
      pathogenesis of arthritis.
AB  - OBJECTIVE: To examine the roles of STATs 1 and 3 in CCL2 production in human
      osteoblastic cells and their influences on arthritis development. METHODS: The
      expression of CCL2 in primary human osteoblasts and U2OS human osteoblastic cells
      was examined by Northern blotting and enzyme-linked immunosorbent assay. The
      roles of STAT-1/3 and c-Fos were assessed using short hairpin RNAs (shRNA) to
      silence their functions. Serine phosphorylation of STATs was assessed by Western
      blotting. Promoter activities of c-Fos and CCL2 were assessed by chloramphenicol
      acetyltransferase and luciferase assays, respectively. Interactions of STAT-1,
      STAT-3, and c-Fos with DNA were evaluated by electrophoretic mobility shift assay
      (EMSA) and immunoprecipitation. The effect of the JAK inhibitor AG-490 on
      collagen-induced arthritis (CIA) in rats was examined using immunohistochemistry.
      RESULTS: Oncostatin M (OSM) stimulated CCL2 expression in primary human
      osteoblasts and U2OS cells. In U2OS cells, STAT-1 and STAT-3 were involved in OSM
      stimulated CCL2 expression, and both the phosphatidylinositol 3-kinase/Akt and
      MEK/ERK pathways were implicated in the activation of these STATs. STAT-1 and
      STAT-3 modulated the expression of c-Fos and directly transactivated the CCL2
      promoter. Moreover, EMSA showed formation of a DNA-protein complex containing
      STAT-1, STAT-3, and interestingly, c-Fos. Immunoprecipitation confirmed the
      binding between c-Fos and STAT-1/3. Reporter assay revealed synergistic
      attenuation of CCL2 promoter activity by shRNA targeting of STAT-1, STAT-3, and c
      Fos. AG-490 suppressed OSM-stimulated activation of STAT-1/3 and synthesis of
      CCL2 in vitro and diminished the severity of CIA and the number of CCL2
      synthesizing osteoblasts in vivo. CONCLUSION: These findings show that multiple
      levels of STAT-1/3 signaling modulate OSM-stimulated CCL2 expression in human
      osteoblastic cells. Clinically, this pathway may be related to the pathogenesis
      of arthritis.

PMID- 19404963
TI  - Cadherin 11 promotes invasive behavior of fibroblast-like synoviocytes.
AB  - OBJECTIVE: To define the expression pattern of cadherin 11 in the destructive
      pannus tissue of patients with rheumatoid arthritis, and to determine whether
      cadherin 11 expression in fibroblast-like synoviocytes controls their invasive
      capacity. METHODS: Cadherin 11 expression in rheumatoid synovial tissue was
      evaluated using immunohistochemistry. To examine the role of cadherin 11 in
      regulating the invasive behavior of fibroblast-like synoviocytes, we generated L
      cell clones expressing wild-type cadherin 11, mutant cadherin 11, and empty
      vector-transfected controls. The invasive capacity of L cell transfectants and
      cultured fibroblast-like synoviocytes treated with a blocking cadherin 11-Fc
      fusion protein or control immunoglobulin was determined in Matrigel invasion
      assays. RESULTS: Immunohistochemical analysis revealed that cadherin 11 is
      abundantly expressed in cells at the cartilage-pannus junction in rheumatoid
      synovitis. Assays to determine invasion demonstrated a 2-fold increased invasive
      capacity of cadherin 11-transfected L cells compared with L cells transfected
      with E-cadherin or control vector. The invasive behavior of L cells stably
      transfected with a cadherin 11 construct that lacked the juxtamembrane
      cytoplasmic domain was diminished to the level of vector control L cells.
      Furthermore, treatment with the cadherin 11-Fc fusion protein diminished the
      invasive capacity of fibroblast-like synoviocytes. CONCLUSION: The results of
      these in vitro studies implicate a role for cadherin 11 in promoting cell
      invasion and contribute insight into the invasive nature of fibroblast-like
      synoviocytes in chronic synovitis and rheumatoid arthritis.

PMID- 19404961
TI  - Gene expression profiling in neutrophils from children with polyarticular
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: We have previously reported a defect in neutrophil activation in
      children with polyarticular juvenile idiopathic arthritis (JIA). The current
      study was undertaken to determine whether gene expression abnormalities persist
      in JIA in remission and to use systems biology analysis to elucidate pathologic
      pathways in polyarticular JIA. METHODS: We performed gene expression profiling on
      neutrophils from children with polyarticular JIA. Children were grouped according
      to disease status. We studied 14 children with active disease who were taking
      medication, 8 children with clinical remission of disease who were taking
      medication (CRM status), and 6 children with clinical remission of disease who
      were not taking medication (CR status). We also studied 13 healthy children whose
      age ranges overlapped those of the patients. RESULTS: Neutrophil abnormalities
      persisted in children with polyarticular JIA even after disease remission was
      achieved. Children with active disease and those with CRM status showed no
      differences in expression of specific genes, although they could be separated on
      cluster analysis. A comparison of children with CR status and healthy control
      children revealed networks of pro- and antiinflammatory genes that suggested that
      remission is a state of homeostasis and balance rather than a return to normal
      immune function. Furthermore, gene overexpression in patients with CR status
      supports the hypothesis that neutrophils play a role in regulating adaptive
      immunity in this disease. CONCLUSION: Neutrophil gene profiling in polyarticular
      JIA suggests important roles for neutrophils in disease pathogenesis. These
      findings suggest the presence of complex interactions between innate and adaptive
      immunity, that are not easily modeled in conventional, linear, reductionist
      systems.

PMID- 19404964
TI  - Rituximab is effective in the treatment of refractory ophthalmic Wegener's
      granulomatosis.
AB  - OBJECTIVE: To investigate the efficacy of rituximab in patients with refractory
      ophthalmic Wegener's granulomatosis (WG). METHODS: Data from 10 consecutive
      patients with refractory ophthalmic WG treated with rituximab were
      retrospectively reviewed. In all patients, the ophthalmic disease was driving
      treatment decisions, and disease activity had persisted despite standard
      immunosuppressive treatment. Patients had refractory scleritis (n=3), orbital
      granulomas causing optic nerve compromise (n=4), or a combination of both
      conditions (n=3). All patients had been treated with at least 3 different
      immunosuppressive agents, and 5 patients had previously been treated with tumor
      necrosis factor alpha blockade. Rituximab was administered intravenously in 2
      doses, 2 weeks apart, in combination with standard treatment. Disease activity
      was monitored clinically by an interdisciplinary approach, including disease
      activity scoring, immunodiagnostics, and magnetic resonance imaging, as well as
      by corresponding reductions in the required dose of conventional medication.
      RESULTS: A beneficial response to treatment with rituximab was seen in all 10
      patients, including induction of clinical remission. In all patients, the
      peripheral blood B cell count fell to zero during treatment with rituximab.
      Titers of classic antineutrophil cytoplasmic antibodies fell in association with
      B cell counts, and this reduction was correlated with improved clinical findings.
      CONCLUSION: In contrast to previous observations, this study showed that
      treatment with rituximab was associated with clinical improvement in patients
      with refractory ophthalmic WG.

PMID- 19404965
TI  - Transmembrane BAFF from rheumatoid synoviocytes requires interleukin-6 to induce
      the expression of recombination-activating gene in B lymphocytes.
AB  - OBJECTIVE: B cells that accumulate in the synovial tissue of rheumatoid arthritis
      (RA) patients revise their receptors due to coordinate expression of
      recombination-activating gene 1 (RAG-1) and RAG-2 genes. The aim of this study
      was to determine the mechanisms that control this re-expression. METHODS: B cells
      from healthy control subjects were cocultured with fibroblast-like synoviocytes
      (FLS) from patients with RA and osteoarthritis (OA). Re-expression of RAG
      messenger RNA (mRNA) and proteins was analyzed by reverse transcription
      polymerase chain reaction (RT-PCR) and indirect immunofluorescence. Activity of
      RAG enzymes was evaluated by flow cytometry to measure variations in
      immunoglobulin kappa and lambda light chain expression and by ligation-mediated
      PCR to assess specific DNA breaks. Blocking antibodies, short hairpin RNA, and
      recombinant cytokine were used to identify the molecules involved in RAG re
      expression. RESULTS: RA FLS, but not OA FLS, induced B cells to re-express RAG
      mRNA and proteins. Enzymes were functional, since the kappa-to-lambda ratios
      decreased and specific DNA breaks were detectable after coculture with RA FLS.
      Transmembrane BAFF provided the first signal of RAG re-expression, since its down
      regulation in RA FLS prevented RAG gene transcription in B cells. The failure of
      transmembrane BAFF from OA FLS to induce RAG suggests that a second signal was
      provided by RA FLS. Interleukin-6 (IL-6) is a candidate, since blockade of its
      receptors precluded transcription of RAG genes by RA FLS. Unless supplemented
      with IL-6, OA FLS were unable to induce RAG gene expression in normal B cells.
      CONCLUSION: Two independent signals are required for the induction of RAG gene
      expression in B cells that infiltrate the synovium of patients with RA.

PMID- 19404966
TI  - Th17 and natural Treg cell population dynamics in systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the relative abundance and activities of Th17 cells and
      natural Treg cells in systemic lupus erythematosus (SLE). METHODS: Blood samples
      were collected from 50 adult patients with SLE. Samples were processed to detect
      Th17 cells and natural Treg cells by flow cytometry, and related gene expression
      was assessed by real-time reverse transcription-polymerase chain reaction. Skin
      biopsy specimens were collected for histologic assessment. The function of Th17
      cells in relation to human umbilical vein endothelial cells (HUVECs) was studied
      in vitro. Th17 cells were also examined in lupus-prone MRL/Mp-lpr/lpr (MRL/lpr)
      mice. RESULTS: We demonstrated the presence of Th17 cells among the peripheral
      blood mononuclear cells (PBMCs) and in the involved organs of patients with
      active SLE. Both the percentage of circulating Th17 cells and the ability to
      produce interleukin-17A (IL-17A) were increased in samples derived from patients
      with active SLE. The number of Th17 cells increased during SLE flare, especially
      in patients with vasculitis, and decreased following certain treatments. We
      observed that IL-17A from patients with SLE could induce adhesion molecule
      messenger RNA expression in HUVECs and adhesion of T cells to HUVECs. An increase
      in the percentage of Th17 cells was correlated with natural Treg cell depletion
      during disease flare. Finally, expansion of the Th17 cell population was detected
      in MRL/lpr mice. CONCLUSION: SLE flare might be linked to the expansion of the
      Th17 cell population and the depletion of natural Treg cell subpopulations.
      Expansion of the Th17 cell population might be related to a distinct cytokine
      environment in active SLE. Th17 cells and microenvironmental IL-17A are involved
      in vascular inflammation in SLE. Antagonism of Th17 cells by IL-17A-blocking
      antibodies should be explored as a treatment of SLE.

PMID- 19404967
TI  - Confirmation of STAT4, IL2/IL21, and CTLA4 polymorphisms in rheumatoid arthritis.
AB  - OBJECTIVE: Recent advances have led to novel identification of genetic
      polymorphisms that are associated with susceptibility to rheumatoid arthritis
      (RA). Currently, 5 loci (HLA, PTPN22, TRAF1/C5, TNFAIP3, and STAT4) have been
      consistently reported, whereas others have been observed less systematically. The
      aim of the present study was to independently replicate 3 recently described RA
      susceptibility loci, STAT4, IL2/IL21, and CTLA4, in a large Dutch case-control
      cohort, and to perform a meta-analysis of all published studies to date and
      investigate the relevance of the findings in clinically well-defined subgroups of
      RA patients with or without autoantibodies. METHODS: The STAT4, IL2/IL21, and
      CTLA4 gene polymorphisms (rs7574865, rs6822844, and rs3087243, respectively) were
      genotyped in 877 RA patients and 866 healthy individuals. A meta-analysis of all
      published studies of disease association with these polymorphisms was performed
      using the Mantel-Haenszel fixed-effects method. RESULTS: An association of STAT4,
      IL2/IL21, and CTLA4 with RA was detected in Dutch patients (odds ratio [OR] 1.19
      [P=0.031], OR 0.84 [P=0.051], and OR 0.87 [P=0.041], respectively). Results from
      the meta-analysis confirmed an association of all 3 polymorphisms with RA in
      Caucasians (OR 1.24 [P=1.66x10(-11)], OR 0.78 [P=5.6x10(-5)], and OR 0.91
      [P=1.8x10(-3)], respectively). The meta-analysis also revealed that STAT4
      predisposed to disease development equally in patients with autoantibodies and
      those without autoantibodies, and that CTLA4 enhanced the development of anti
      citrullinated protein antibody (ACPA)-positive RA as compared with ACPA-negative
      RA. CONCLUSION: Our results replicate and firmly establish the association of
      STAT4 and CTLA4 with RA and provide highly suggestive evidence for IL2/IL21 loci
      as a risk factor for RA. Given the strong statistical power of our meta-analysis
      to confirm a true-positive association, these findings provide considerable
      support for the involvement of CTLA4 in distinct subsets of RA patients.

PMID- 19404968
TI  - The dynamics of macrophage lineage populations in inflammatory and autoimmune
      diseases.

PMID- 19404973
TI  - Should patients with rheumatoid arthritis receive statin therapy?

PMID- 19404974
TI  - Effect of ciprofloxacin-mediated inhibition on cell proliferation in rat tendon
      cells: comment on the article by Tsai et al.

PMID- 19404975
TI  - Clinical images: Podoconiosis: foot edema resulting from regional geochemistry.

PMID- 19404976
TI  - Clinical images: Gout attack and stiff knee in an airline passenger in economy
      class.

PMID- 19404977
TI  - Mann-Whitney U test and Kruskal-Wallis test should be used for comparisons of
      differences in medians, not means: comment on the article by van der Helm-van Mil
      et al.

PMID- 19404978
TI  - Defensin-related peptide 1 (Defr1) is allelic to Defb8 and chemoattracts immature
      DC and CD4+ T cells independently of CCR6.
AB  - Beta-defensins comprise a family of cationic, antimicrobial and chemoattractant
      peptides. The six cysteine canonical motif is retained throughout evolution and
      the disulphide connectivities stabilise the conserved monomer structure. A murine
      beta-defensin gene (Defr1) present in the main defensin cluster of C57B1/6 mice,
      encodes a peptide with only five of the canonical six cysteine residues. In other
      inbred strains of mice, the allele encodes Defb8, which has the six cysteine
      motif. We show here that in common with six cysteine beta-defensins, defensin
      related peptide 1 (Defr1) displays chemoattractant activity for CD4(+) T cells
      and immature DC (iDC), but not mature DC cells or neutrophils. Murine Defb2
      replicates this pattern of attraction. Defb8 is also able to attract iDC but not
      mature DC. Synthetic analogues of Defr1 with the six cysteines restored (Defr1
      Y5C) or with only a single cysteine (Defr1-1c(V)) chemoattract CD4(+) T cells
      with reduced activity, but do not chemoattract DC. Beta-defensins have previously
      been shown to attract iDC through CC receptor 6 (CCR6) but neither Defr1 or its
      related peptides nor Defb8, chemoattract cells overexpressing CCR6. Thus, we
      demonstrate that the canonical six cysteines of beta-defensins are not required
      for the chemoattractant activity of Defr1 and that neither Defr1 nor the six
      cysteine polymorphic variant allele Defb8, act through CCR6.

PMID- 19404979
TI  - DNAX accessory molecule-1 (CD226) promotes human hepatocellular carcinoma cell
      lysis by Vgamma9Vdelta2 T cells.
AB  - Human Vgamma9Vdelta2 T lymphocytes can be activated by nonpeptidic antigens such
      as the mevalonate pathway-derived isopentenyl pyrophosphate or synthetic
      phosphoantigen such as bromohydrin pyrophosphate. They display a strong cytotoxic
      activity against several tumor types, including hepatocellular carcinoma (HCC).
      Little is known about the mechanisms underlying Vgamma9Vdelta2 T-cell recognition
      of tumor cells, but there is strong evidence that activating NK receptors play a
      role in gammadelta T-cell cytotoxicity. In this study, we showed that the two NK
      receptors DNAX accessory molecule-1 (DNAM-1) and CD96 were expressed by
      Vgamma9Vdelta2 T cells. The ligands Nectin-like-5 specific of both DNAM-1 and
      CD96, and also Nectin-2, an additional ligand of DNAM-1, were present on all HCC
      cell lines analyzed. Furthermore, we demonstrated by mAb-mediated masking
      experiments that cytotoxicity against HCC cells as well as IFN-gamma production
      in gammadelta T cells were dependent on DNAM-1. Our experiments indicated that
      Nectin-like-5 but not Nectin-2 was involved in DNAM-1-dependent gammadelta T-cell
      functions. We did not reveal a role for CD96 in the killing of HCC cells.
      Finally, we showed by combined mAb-mediated blockade that DNAM-1 and NKG2D could
      cooperate in the cell lysis of HCC.

PMID- 19404981
TI  - Clonal dissection of the human memory B-cell repertoire following infection and
      vaccination.
AB  - The analysis of the human memory B-cell repertoire is of both fundamental and
      practical significance. We developed a simple method for the selective activation
      of memory B cells in total fresh or frozen PBMC using a combination of R848 and
      IL-2. In these conditions, 30-40% of memory B cells generated clones producing on
      average 200 ng IgG in 10 days. This method was used to measure the frequency of
      antigen-specific memory B cells as well as the fine specificity, cross-reactivity
      and neutralizing activity of the secreted antibodies. Following influenza
      vaccination, specific B cells expanded dramatically, reaching up to 50% of total
      clonable memory B cells on day 14. Specific B-cell expansions were detected also
      in individuals that did not show a significant serological response. Dynamic
      changes and persistence of B cells specific for a variety of pathogens were
      documented in serial PBMC samples collected over almost two decades. These
      results reveal novel aspects of memory B-cell kinetics and provide a powerful
      tool to monitor immune responses following infection and vaccination.

PMID- 19404982
TI  - Regulatory T cells enter the pancreas during suppression of type 1 diabetes and
      inhibit effector T cells and macrophages in a TGF-beta-dependent manner.
AB  - Treg can suppress autoimmune diseases such as type 1 diabetes, but their in vivo
      activity during suppression remains poorly characterized. In type 1 diabetes,
      Treg activity has been demonstrated in the pancreatic lymph node, but little has
      been studied in the pancreas, the site of autoimmune islet destruction. In this
      study we induced islet-specific Treg from the BDC-6.9 TCR transgenic mouse by
      activation of T cells in the presence of TGF-beta. These Treg can suppress
      spontaneous diabetes as well as transfer of diabetes into NOD.scid mice by
      diabetic NOD spleen cells or activated BDC-2.5 TCR transgenic Th1 effector T
      cells. In the latter transfer model, we observed infiltration of the pancreas by
      both effector T cells and Treg, suggesting that Treg are active in the
      inflammatory site and are not just restricted to the draining lymph node. Within
      the pancreas, we demonstrate that Treg transfer causes a reduction in the number
      of effector Th1 T cells and macrophages, and also inhibits effector T-cell
      cytokine and chemokine production. Although we found no role for TGF-beta in
      vitro, transfection of effector T cells with a dominant-negative TGF-beta
      receptor demonstrated that in vivo suppression of diabetes by TGF-beta-induced
      Treg is TGF-beta-dependent.

PMID- 19404986
TI  - Immunology and the biomedical student pipeline.

PMID- 19404984
TI  - Requirement of phospholipase C-gamma2 (PLCgamma2) for Dectin-1-induced antigen
      presentation and induction of TH1/TH17 polarization.
AB  - DC recognize microbial components through an array of receptors known as PRR. PRR
      initiate intracellular signals, which engender DC with the capacity to stimulate
      T-cell responses. Dectin-1 is a PRR that recognizes beta-glucan, a major
      constituent of many fungi's outer cell wall. Here we show that Dectin-1 activates
      DC through phospholipase (PLC)gamma2 signaling. PLCgamma2-deficient DC were
      unable to expand antigen-specific T cells and induce T(H)1 and T(H)17
      differentiation in response to beta-glucan. Mechanistically, PLCgamma2-deficiency
      impaired the capacity of DC to secrete polarizing cytokines following exposure to
      beta-glucan. Dectin-1 required PLCgamma2 to activate MAPK, AP-1 and NF-kappaB,
      which induce cytokine gene expression. Moreover, PLCgamma2 controlled Dectin-1
      mediated NFAT activation and induction of NFAT-dependent genes such as IL-2,
      cyclooxigenase-2 and Egr transcription factors. We conclude that PLCgamma2 is a
      crucial signaling mediator that modifies DC gene expression program to activate
      DC responses to beta-glucan-containing pathogens.

PMID- 19404987
TI  - Shine a light: imaging the immune system.
AB  - Intra vital microscopy and whole-body imaging promise to revolutionize how we
      study the immune system. They compel by the intrinsic beauty of the images
      obtained and the undeniable direct biological relevance of the observations.
      However, it is important to remember that in many cases, fundamental insights
      into the underlying biological processes have already been obtained using ex vivo
      reductionist approaches. Indeed, it is likely that with the advent of
      microfluidics, new and exciting avenues will open up for ex vivo experimentation.
      Here, we give a brief but comprehensive overview of the various imaging
      techniques available, their relative strengths and shortcomings and how these
      tools have been used to get us to where we are today. The challenge for the
      future will be to apply the most suitable technology and to integrate the
      findings across various imaging disciplines to build a unified, comprehensive
      "big picture" of the immune system.

PMID- 19404988
TI  - Granzyme A expression reveals distinct cytolytic CTL subsets following influenza
      A virus infection.
AB  - CTL mediate anti-viral immunity via targeted exocytosis of cytolytic granules
      containing perforin and members of the granzyme (grz) serine protease family.
      Here, we provide the first analysis of grzA protein expression by murine anti
      viral CTL. During the progression of influenza A virus infection, CTL expressed
      two divergent cytolytic phenotypes: grzA(-)B(+) and grzA(+)B(+). CTL lacked grzA
      expression during the initial rounds of antigen-driven division. High levels of
      grzA were expressed by influenza-specific CTL early post infection (day 6),
      particularly in tissues associated with the infected respiratory tract
      (bronchoalveolar lavage, lung). Following resolution of influenza infection, a
      small population of memory CTL expressed grzA. Interestingly, individual
      influenza A virus-derived epitope-specific CTL expressed different levels of
      grzA. The grzA expression hierarchy was determined to be
      K(b)PB1(703)=D(b)F2(62)=K(b)NS2(114)>D(b)NP(366)=D(b)PA(224) and inversely
      correlated with CTL magnitude. Therefore following influenza infection, a CTL
      cytolytic hierarchy was established relating to the different profiles of antigen
      expression and relative immunodominance. Analysis of CTL grzA expression during
      influenza virus immunity has enabled a more detailed insight into the cytolytic
      mechanisms of virus elimination.

PMID- 19404989
TI  - Treatment of adolescent depression: what we have come to know.

PMID- 19404990
TI  - Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis:
      revisited.
AB  - Voxel-based analyses (VBA) are increasingly being used to detect white matter
      abnormalities with diffusion tensor imaging (DTI) in different types of
      pathologies. However, the validity, specificity, and sensitivity of statistical
      inferences of group differences to a large extent depend on the quality of the
      spatial normalization of the DTI images. Using high-dimensional nonrigid
      coregistration techniques that are able to align both the spatial and
      orientational diffusion information and incorporate appropriate templates that
      contain this complete DT information may improve this quality. Alternatively, a
      hybrid technique such as tract-based spatial statistics (TBSS) may improve the
      reliability of the statistical results by generating voxel-wise statistics
      without the need for perfect image alignment and spatial smoothing. In this
      study, we have used (1) a coregistration algorithm that was optimized for
      coregistration of DTI data and (2) a population-based DTI atlas to reanalyze our
      previously published VBA, which compared the fractional anisotropy and mean
      diffusivity maps of patients with amyotrophic lateral sclerosis (ALS) with those
      of healthy controls. Additionally, we performed a complementary TBSS analysis to
      improve our understanding and interpretation of the VBA results. We demonstrate
      that, as the overall variance of the diffusion properties is lowered after
      normalizing the DTI data with such recently developed techniques (VBA using our
      own optimized high-dimensional nonrigid coregistration and TBSS), more reliable
      voxel-wise statistical results can be obtained than had previously been possible,
      with our VBA and TBSS yielding very similar results. This study provides support
      for the view of ALS as a multisystem disease, in which the entire frontotemporal
      lobe is implicated.

PMID- 19404991
TI  - Neural correlates of the females' susceptibility to negative emotions: an insight
      into gender-related prevalence of affective disturbances.
AB  - Considerable studies reported that females are more susceptible to affective
      disturbances such as depression, anxiety disorder, and phobia compared to males.
      Based on the close relation between emotional sensitivity and liability to
      affective disturbances (Hofer et al. [2006]: NeuroImage 32, 854-862; Spearing
      [2001]: Bipolar disorder, 2nd ed. Bethesda (MA): National institute of Mental
      Health), this study investigated the neural mechanism underlying the females'
      liability to affective disturbances by hypothesizing that females are more
      susceptible to negative emotions than males. Event-related potentials (ERPs) were
      recorded for highly negative (HN), moderately negative (MN), and neutral images
      in Experiment 1, and for highly positive, moderately positive, and neutral images
      in Experiment 2, whereas subjects (15 males and 15 females) performed a
      standard/deviant distinction task, irrespective of the emotional valence of
      deviants in both experiments. In addition to the prominent emotional reactions
      evoked by HN stimuli in both genders, Experiment 1 displayed conspicuous
      emotional responses of females to MN stimuli across N2 and P3 components, which
      were absent in males. In contrast, Experiment 2 demonstrated neither significant
      valence effect, nor significant valence by gender interaction effect at these
      components. Thus, although both genders are sensitive to HN stimuli, females,
      instead of males, are particularly susceptible to negative stimuli of lesser
      salience, and this female specific susceptibility does not exist to the positive
      stimuli. Therefore, females must be more susceptible to negative emotions in life
      settings, which may be one important mechanism underlying their higher prevalence
      of affective disturbances.

PMID- 19404992
TI  - Nanochemistry: what is next?

PMID- 19404993
TI  - Ex vivo expansion of adipose tissue-derived stem cells in spinner flasks.
AB  - Recent reports indicate that adipose tissue is a novel source of multipotent stem
      cells that can be used in cell therapy and tissue engineering. However, using the
      traditional cultivation of adipose tissue-derived stem cells (ADSCs), it is hard
      to meet the needs of clinical applications. To obtain a large number of ADSCs
      while retaining their stemness, we seeded ADSCs in collagen/chitosan scaffolds
      and compared the proliferation of ADSCs in a 3-D static environment in dishes and
      a 3-D dynamic environment in spinner flask. The growth dynamic parameters of
      ADSCs were examined using a CCK-8 kit every other day, and the variations of
      glucose and lactic acid concentrations were analyzed every day. After 14 days,
      the cells were observed under a scanning electron microscope. The surface markers
      (CD29, CD34, CD44, CD45, CD73, CD105, CD166 and HLA-DR), the specific
      transcription factors (Nanog, Oct-4, Sox-2 and Rex-1) and the multi
      differentiation potential (adipogenic, osteogenic and chondrogenic) were also
      assayed to identify the stemness of expanded cells. The results showed that the
      cells in scaffolds in spinner flask could be expanded by more than 26 times, and
      they presented better morphology and vitality and stronger differentiation
      ability than the cells cultivated in scaffolds statically. All the cells
      maintained stem cell characteristics after proliferation. Therefore, spinner
      flask cultivation is an easy-to-use, inexpensive system for expanding ADSCs in 3
      D scaffolds.

PMID- 19404997
TI  - Predicting depression in rheumatoid arthritis: the signal importance of pain
      extent and fatigue, and comorbidity.
AB  - OBJECTIVE: To determine the incidence of self-reported depression (SRD) in
      rheumatoid arthritis and to identify and rank clinically useful predictors of
      depression. METHODS: We assessed 22,131 patients for SRD between 1999 and 2008.
      We collected demographic, clinical and treatment data, household income,
      employment and work disability status, comorbidity, scales for function, pain,
      global, and fatigue, the Regional Pain Scale (RPS), the Symptom Intensity (SI)
      scale (a linear combination of the RPS and the fatigue scales) and linear
      combinations of the Health Assessment Questionnaire, pain and global severity. We
      used logistic regression analyses with multivariable fractional polynomial
      predictors, and Random Forest analysis to determine the importance of the
      predictors. RESULTS: The cross-sectional prevalence of self-reported depression
      was 15.2% (95% confidence interval [95% CI] 14.7-15.7%) and the incidence rate
      was 5.5 (95% CI 5.3-5.7) per 100 patient years of observation. The cumulative
      risk of SRD after 9 years was 38.3% (95% CI 36.6-40.1%). Almost all variables
      were significant predictors in logistic models. In Random Forest analyses, the SI
      scale, followed by comorbidity, best predicted self-reported depression, and no
      other variable or combination of variables improved prediction compared with the
      SI scale. CONCLUSION: Pain extent and fatigue (SI scale) are the dominant
      predictors of SRD. These variables, also of central importance in the
      symptomatology of fibromyalgia, are powerful markers of distress. A strong case
      can be made for the inclusion of these assessments in routine rheumatology
      practice. In addition, actual knowledge of comorbidity provides important
      insights into the patient's global health and associated perceptions.

PMID- 19404994
TI  - Functional status of men with the fragile X premutation, with and without the
      tremor/ataxia syndrome (FXTAS).
AB  - BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS), which occurs in
      some premutation carriers of the fragile X mental retardation 1 (FMR1) gene, is a
      neurodegenerative disorder characterized by action tremor, gait ataxia, and
      impaired executive cognitive functioning. OBJECTIVE: To evaluate the nature and
      severity of functional limitations among male carriers of the fragile X
      premutation, both with and without FXTAS. METHODS: Forty-two subjects with FXTAS
      and 24 asymptomatic premutation carriers were compared to 32 control subjects on
      measures of physical functioning, activities of daily living (ADLs; e.g. eating,
      bathing), and instrumental activities of daily living (IADLs; e.g. shopping,
      managing medications). Ordinary least squares regression, controlling for age,
      education, medical comorbidity, and pain, was used to examine group differences
      in physical and functional performance. RESULTS: Men with FXTAS performed
      significantly worse than control subjects on all dependent measures, showing
      greater limitations in physical functioning, as well as ADL and IADL performance
      (p < 0.05). Subsequent analyses suggested that physical and functional
      impairments among men with FXTAS result largely from deficits in motor and
      executive functioning and that CGG repeat length is associated with functional
      impairment. Asymptomatic carriers of the fragile X premutation performed
      similarly to control subjects on all measures. CONCLUSIONS: This study provides
      the first comprehensive evaluation of functional status among male premutation
      carriers. Although carriers without FXTAS performed similarly to control
      subjects, men with FXTAS showed evidence of significant physical and functional
      impairment, which appears to result largely from motor and executive deficits
      characteristic of the syndrome.

PMID- 19404998
TI  - Do acute-phase reactants predict response to glucocorticoid therapy in
      retroperitoneal fibrosis?
AB  - OBJECTIVE: To determine the value of the erythrocyte sedimentation rate (ESR) and
      the C-reactive protein (CRP) level at the time of diagnosis for predicting
      radiographic response to glucocorticoid therapy in patients with retroperitoneal
      fibrosis (RFP). METHODS: Data were collected retrospectively for 37 patients with
      an established diagnosis of RFP (the diagnosis was proven by biopsy in 31
      patients), all of whom met the following inclusion criteria: 1) availability of a
      recorded baseline ESR and/or CRP level and results of computed tomography or
      magnetic resonance imaging, 2) availability of followup CRP level and/or ESR with
      radiographic imaging 12-24 weeks after initiation of therapy, and 3) treatment
      with prednisone monotherapy at a starting dosage of 40-60 mg daily. Patients were
      divided into 2 therapeutic response groups: group 1 showed radiographic
      regression, and group 2 showed no change or radiographic progression. Any
      progression or regression was determined by an estimated change of > or =25%.
      RESULTS: The median baseline CRP levels were 2.2 mg/dl (interquartile range [IQR]
      1.4-8.0) in group 1 and 1.2 mg/dl (IQR 0.8-4.1) in group 2 (P = 0.35). The median
      baseline ESR in group 1 was 57.5 mm/hour (IQR 39.2-102.5), which was not
      statistically different from the median ESR in group 2 (58 mm/hour [IQR 33-66]).
      The mean CRP level and ESR tended to be higher in patients with radiographic
      regression, but these differences failed to reach statistical significance.
      Spearman's correlation coefficient revealed no correlation between the baseline
      CRP level (r = -0.11, P = 0.51) or ESR (r = -0.06, P = 0.71) and the radiographic
      response. CONCLUSION: The ESR and CRP level at baseline are poor predictors of a
      therapeutic response to glucocorticoid therapy in patients with RPF.

PMID- 19404999
TI  - Biologic therapy and pregnancy outcomes in women with rheumatic diseases.

PMID- 19405000
TI  - Comparison of drug retention rates and causes of drug discontinuation between
      anti-tumor necrosis factor agents in rheumatoid arthritis.
AB  - OBJECTIVE: Tumor necrosis factor (TNF) inhibitors have revolutionized the
      treatment of severe rheumatoid arthritis (RA), yet drug discontinuation is
      common. The aim of this study was to compare treatment retention rates and
      specific causes of anti-TNF discontinuation in a population-based RA cohort.
      METHODS: All patients treated with etanercept, infliximab, or adalimumab within
      the Swiss Clinical Quality Management RA cohort between 1997 and 2006 were
      included in the study. Causes of treatment discontinuation were broadly
      categorized as adverse events (AEs) or nontoxic causes, and further subdivided
      into specific categories. Specific causes of treatment interruption were analyzed
      using a Cox proportional hazards model and adjusted for potential confounders.
      RESULTS: A total of 2,364 anti-TNF treatment courses met the inclusion criteria.
      Treatment discontinuation was reported 803 times: 309 with etanercept, 249 with
      infliximab, and 245 with adalimumab. Drug inefficacy represented the largest
      single cause of treatment discontinuation (55.8% of cases). The median time of
      receiving anti-TNF therapy was 37 months, but discontinuation rates differed
      between the 3 anti-TNF agents (P < 0.001), with shorter retention rates for
      infliximab (hazard ratio [HR] 1.24, 99% confidence interval [99% CI] 1.01-1.51).
      The specific causes of treatment discontinuation revealed an increased risk of
      AEs with infliximab (HR 1.4, 99% CI 1.003-1.96), mostly due to an increased risk
      of infusion or allergic reactions (HR 2.11, 99% CI 1.23-3.62). Other
      discontinuation causes were equally distributed between the anti-TNF agents.
      CONCLUSION: In this population, infliximab was associated with higher overall
      discontinuation rates compared with etanercept and adalimumab, which is mainly
      due to an increased risk of infusion or allergic reactions.

PMID- 19405001
TI  - The high prevalence of knee osteoarthritis in a rural Chinese population: the
      Wuchuan osteoarthritis study.
AB  - OBJECTIVE: To estimate the prevalence of radiographic and symptomatic knee
      osteoarthritis (OA) in a remote rural region of northern China, and compare them
      with those reported in Beijing and with data from the Framingham (Massachusetts)
      cohort. METHODS: A population-based cross-sectional survey was conducted among
      1,030 residents of Wuchuan County, Inner Mongolia, age > or =50 years. Survey
      participants, mostly farmers reporting heavy physical occupational activity,
      completed an interviewer-based questionnaire, and bilateral weight-bearing
      posteroanterior semiflexed knee radiographs were obtained. RESULTS: Whereas the
      overall prevalence of radiographic knee OA was similar to that demonstrated in
      the Beijing OA study, men in Wuchuan had approximately double the prevalence of
      severe radiographic knee OA (prevalence ratio [PR] 2.5, 95% confidence interval
      [95% CI] 1.6-3.8) and symptomatic knee OA (PR 1.9, 95% CI 1.3-2.9). Women in
      Wuchuan also had a higher prevalence of both severe radiographic (PR 1.4, 95% CI
      1.0-2.0) and symptomatic knee OA (PR 1.6, 95% CI 1.2-2.1) compared with their
      Beijing counterparts. The prevalence of bilateral OA and lateral compartment
      disease were 2-3 times higher in both Chinese cohorts compared with estimates
      from the Framingham OA study. CONCLUSION: The prevalence of symptomatic knee OA
      in rural areas of China is much higher than reported from urban regions of China
      or in the Framingham cohort. The higher representation of bilateral and lateral
      compartment disease in China suggests a unique phenotype to OA. These findings
      will be useful for guiding the distribution of future health care resources and
      preventive strategies.

PMID- 19405002
TI  - Problems experienced by people with arthritis when using a computer.
AB  - OBJECTIVE: To describe the prevalence of computer use problems experienced by a
      sample of people with arthritis, and to determine differences in the magnitude of
      these problems among people with rheumatoid arthritis (RA), osteoarthritis (OA),
      and fibromyalgia (FM). METHODS: Subjects were recruited from the Arthritis
      Network Disease Registry and asked to complete a survey, the Computer Problems
      Survey, which was developed for this study. Descriptive statistics were
      calculated for the total sample and the 3 diagnostic subgroups. Ordinal
      regressions were used to determine differences between the diagnostic subgroups
      with respect to each equipment item while controlling for confounding demographic
      variables. RESULTS: A total of 359 respondents completed a survey. Of the 315
      respondents who reported using a computer, 84% reported a problem with computer
      use attributed to their underlying disorder, and approximately 77% reported some
      discomfort related to computer use. Equipment items most likely to account for
      problems and discomfort were the chair, keyboard, mouse, and monitor. Of the 3
      subgroups, significantly more respondents with FM reported more severe
      discomfort, more problems, and greater limitations related to computer use than
      those with RA or OA for all 4 equipment items. CONCLUSION: Computer use is
      significantly affected by arthritis. This could limit the ability of a person
      with arthritis to participate in work and home activities. Further study is
      warranted to delineate disease-related limitations and develop interventions to
      reduce them.

PMID- 19405003
TI  - Development and validation of a composite disease activity score for juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: To develop and validate a composite disease activity score for
      juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity
      Score (JADAS). METHODS: The JADAS includes 4 measures: physician global
      assessment of disease activity, parent/patient global assessment of well-being,
      active joint count, and erythrocyte sedimentation rate. These variables are part
      of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50,
      and Pedi 70 criteria for improvement. Validation analyses were conducted on
      >4,500 patients and included assessment of construct validity, discriminant
      validity, and responsiveness to change. Three versions of the JADAS were tested
      based on 71-joint (range 0-101), 27-joint (range 0-57), or 10-joint (range 0-40)
      counts. Statistical performances of the JADAS were compared with those of 2
      rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints
      (DAS28) and the Clinical Disease Activity Index (CDAI). RESULTS: The JADAS
      demonstrated good construct validity, yielding strong correlations with JIA
      activity measures not included in the score and moderate correlations with the
      Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS
      versions were comparable, but superior to those yielded by the DAS28 and CDAI.
      The area under the curve of the JADAS predicted long-term disease outcome,
      measured as radiographic progression over 3 years. In 2 clinical trials, the
      JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and
      revealed strong responsiveness to clinical change. CONCLUSION: The JADAS was
      found to be a valid instrument for assessment of disease activity in JIA and is
      potentially applicable in standard clinical care, observational studies, and
      clinical trials.

PMID- 19405004
TI  - Cognitive impairment and employment status in systemic lupus erythematosus: a
      prospective longitudinal study.
AB  - OBJECTIVE: To determine the relationship between cognitive impairment and
      employment in patients with systemic lupus erythematosus (SLE). METHODS: A total
      of 167 consecutive patients with SLE were prospectively evaluated, and underwent
      standardized neuropsychological tests. Multivariate logistic regression was used
      to determine the likelihood of being unemployed, adjusting for sociodemographic
      characteristics, employment status at study entry, disease activity, disease
      duration, damage scores, and depression. RESULTS: At study entry, 118 (70.7%) of
      167 patients were employed. In the multivariate analysis, after adjusting for
      confounders, unemployment was predicted by the number of cognitive domains
      impaired (odds ratio [OR] 1.76, 95% confidence interval [95% CI] 1.58-6.72),
      depression (OR 1.3, 95% CI 1.1-3.1), fewer years of education (OR 0.12, 95% CI
      0.02-0.34), and the presence of anticardiolipin antibodies (OR 1.43, 95% CI 1.2
      6.1). Complex attention (OR 1.7, 95% CI 1.2-3.6), memory (OR 3.1, 95% CI 1.5
      6.2), and executive functions (OR 2.4, 95% CI 1.9-6.1) were predictors of
      unemployment at study entry. After 3 years, 61 (51.7%) of 118 patients were
      employed (OR 2.25, 95% CI 1.38-3.68; P = 0.001). The likelihood of being
      unemployed after 3 years was predicted by the number of cognitive domains
      impaired (OR 3.8, 95% CI 2.5-7.71), depression (OR 2.31, 95% CI 1.01-5.21), fewer
      years of education (OR 0.09, 95% CI 0.01-0.42), and the presence of
      anticardiolipin antibodies (OR 2.1, 95% CI 1.2-4.9). Complex attention (OR 2.2,
      95% CI 1.1-3.8), memory (OR 3.6, 95% CI 2.1-6.4), executive functions (OR 1.8,
      95% CI 1.2-7.3), and reasoning/problem solving (OR 1.9, 95% CI 1.4-7.2) were
      associated with unemployment after 3 years. CONCLUSION: The number of cognitive
      spheres, and especially attention, memory, and executive functions, are important
      factors associated with unemployment in patients with SLE.

PMID- 19405005
TI  - Treatment of relapsing polychondritis with rituximab: a retrospective study of
      nine patients.
AB  - OBJECTIVE: Rituximab, a chimeric monoclonal antibody directed against the CD20
      antigen expressed by B cells, is now considered an effective second-line therapy
      in various systemic diseases. We describe here the effects of rituximab in
      patients with relapsing polychondritis. METHODS: This was a retrospective study
      of 9 patients with relapsing polychondritis who received different regimens of
      rituximab in addition to their ongoing therapies. Clinical, laboratory,
      physiologic, and radiologic indicators were used to assess disease activity. We
      also examined their corticosteroid doses and any change in immunosuppressive
      agents. We then compared disease activity in the 6 months preceding rituximab
      administration and at 6 and 12 months after. RESULTS: At 6 months, 2 patients
      showed partial improvement, 4 were stable, and 3 had worsened disease; however,
      no patient had complete remission. At 12 months (after exclusion of the 3
      patients whose disease had worsened at 6 months), 2 patients remained stable and
      4 had worsened disease; however, there were no partial or complete remissions. B
      cells were counted in 8 patients during the first 6 months after treatment, and B
      cell depletion was observed in all of the patients. CONCLUSION: Although we
      cannot rule out the possibility that rituximab had a small effect, our patients'
      clinical courses did not improve significantly with this treatment.

PMID- 19405006
TI  - Defining remission in rheumatoid arthritis: results of an initial American
      College of Rheumatology/European League Against Rheumatism consensus conference.
AB  - OBJECTIVE: Due to advances in rheumatoid arthritis (RA) therapies over the last
      few years, an increasing proportion of patients are able to achieve a state of
      remission. However, the definition of remission is unclear. Currently, randomized
      controlled trials around the world use different remission definitions and
      consequently measure different aspects of a patient's disease state. The need for
      a uniform definition of remission is vital for research findings to be correctly
      interpreted. METHODS: The American College of Rheumatology (ACR) constituted a
      committee that included international clinical researchers, trialists, and
      clinical epidemiologists in order to redefine remission in RA. This group was
      asked to study current definitions of remission, explore the theoretical
      underpinning of the concept of remission, and develop a research agenda that
      would inform future work in the development of an ACR definition of remission.
      RESULTS: In its first meeting, the committee preferred to develop a strict
      definition, implying no or very low disease activity. Such a definition would
      need to be validated against long-term outcome, e.g., physical function and
      damage. CONCLUSION: The committee decided to consider both a definition for
      trials and a modified version for clinical practice. Since the first meeting, the
      ACR and the European League Against Rheumatism (EULAR) have decided to sponsor
      this initiative as an official ACR/EULAR collaboration.

PMID- 19405007
TI  - Capillaroscopic skin ulcer risk index: a new prognostic tool for digital skin
      ulcer development in systemic sclerosis patients.
AB  - OBJECTIVE: Digital ulcerations are one of the most frequent manifestations of
      microangiopathy in patients with systemic sclerosis (SSc; scleroderma). The early
      detection of SSc patients who are at high risk to develop digital ulcers could
      allow a preventive treatment of these complications with reduction of morbidity
      and social costs. The aim of our study was to develop a capillaroscopic skin
      ulcer risk index (CSURI) that can predict the onset of new digital ulcers by
      using nailfold videocapillaroscopy (NVC) in patients with SSc. METHODS: We
      performed NVC in 120 consecutive unselected patients with SSc (13 men, 107 women,
      mean +/- SD age 56.1 +/- 13.4 years, mean +/- SD SSc duration 44.7 +/- 60.7
      months) to assess the total number of capillaries in the distal row (N), maximum
      loop diameter (D), number of megacapillaries (M), and the M:N ratio. RESULTS:
      Within 3 months since NVC examination, 35 of 120 patients experienced digital
      ulcers. A significant association between ischemic lesions and the M:N ratio, N,
      and D was observed; the combination of these parameters allowed us to develop the
      CSURI, which is characterized by the formula D x M:N(2). A receiver operating
      characteristic curve analysis showed an area under the curve of 0.926 for ulcer
      appearance, with specificity and sensitivity of 85.9% and 94.3%, respectively, at
      the cutoff value of 2.94. Interestingly, 33 of 35 patients with new skin ulcers
      had a CSURI >2.94, but only 2 of 35 had a CSURI < or =2.94. CONCLUSION: The
      proposed CSURI may represent a novel tool with the ability to predict the
      development of digital ulcers in patients with scleroderma.

PMID- 19405008
TI  - Measuring shoulder function: a systematic review of four questionnaires.
AB  - OBJECTIVE: To conduct a systematic review of the quality and content of the
      psychometric evidence relating to 4 shoulder disability scales: the Disabilities
      of the Arm, Shoulder, and Hand (DASH) questionnaire, the Shoulder Pain and
      Disability Index (SPADI), the American Shoulder and Elbow Surgeons (ASES) score,
      and the Simple Shoulder Test (SST). METHODS: We conducted a structured search
      using 3 databases (Medline, CINAHL, EMBase). In total, 71 published primary
      studies were analyzed. A pair of raters conducted data extraction and critical
      appraisal using structured tools. A descriptive synthesis was performed. RESULTS:
      Quality ratings of 55% of the studies reviewed reached a level of > or =75%. Most
      studies suggest that all 4 questionnaires have excellent reliability (intraclass
      correlation coefficient > or =0.90). The 4 questionnaires are strongly correlated
      (r >0.70) with each other and with a number of similar indices, and the
      questionnaires were able to differentiate between different populations and
      disability levels. The minimal detectable change (MDC) is approximately 9.4 for
      the ASES, 10.5 for the DASH, and 18 for the SPADI; the minimal clinically
      important difference (MCID) is approximately 6.4 for the ASES and 10.2 for the
      DASH, and ranges between 8 and 13 for the SPADI. MDC and MCID have not been
      defined for the SST. CONCLUSION: The psychometric properties of the ASES, DASH,
      and SPADI have been shown to be acceptable for clinical use. Conversely, some
      properties of the SST still need be evaluated, particularly the absolute errors
      of measurement. Overall, validation studies have focused on less clinically
      relevant properties (construct validity or group reliability) than estimates of
      MDC and MCID.

PMID- 19405009
TI  - An early view of the international Sjogren's syndrome registry.

PMID- 19405010
TI  - Introduction to special section: biologic agents in the treatment of rheumatic
      diseases-the first decade.

PMID- 19405011
TI  - Epidemiology and clinical characteristics of Behcet's disease in the US: a
      population-based study.
AB  - OBJECTIVE: Behcet's disease (BD) is a rare, multisystem inflammatory disorder of
      unknown cause. Although well-documented in Eastern populations, epidemiologic
      data is scarce in North American countries. Here we describe the incidence and
      prevalence of BD in Olmsted County, Minnesota over 45 years. METHODS: We
      identified an incidence cohort of subjects age >/=18 years who had a clinical
      diagnosis of and/or fulfilled the International Study Group (ISG) criteria for BD
      from January 1, 1960 to January 1, 2005. Age- and sex-specific incidence and
      prevalence were estimated and age- and sex-adjusted to the 2000 US total
      population. RESULTS: The study population was comprised of 13 subjects with BD;
      11 fulfilled ISG criteria between 1960 and 2005. Mean +/- SD age was 31 +/- 9
      years, and 69% were white. Point prevalence in 2000 was 5.2 per 100,000
      population (95% confidence interval [95% CI] 0.64-9.84). The overall annual age-
      and sex-adjusted incidence of BD was 0.38 per 100,000 population (95% CI 0.17
      0.59), with a higher incidence in women (0.51 per 100,000; 95% CI 0.17-0.84) than
      in men (0.26 per 100,000; 95% CI 0.004-0.52). Dermatologic lesions included oral
      ulcers (100%), genital ulcers (62%), erythema nodosum (46%), and papulopustular
      lesions (54%). Ocular lesions, vascular complications, and central nervous system
      involvement were present in 8, 3, and 3 subjects, respectively. CONCLUSION: Our
      study shows an overall incidence of 0.38 per 100,000 population, which is
      comparable with other Western populations. The prevalence of 5.2 per 100,000
      population is similar to estimates reported in Western countries, but lower than
      that in countries along the Silk Road.

PMID- 19405012
TI  - Validation of a manual ability questionnaire in patients with systemic sclerosis.
AB  - OBJECTIVE: To adapt and validate a manual ability questionnaire, the ABILHAND,
      developed through the Rasch methodology in patients with systemic sclerosis
      (SSc). METHODS: The original version of the ABILHAND, which includes 81 manual
      daily activities, was presented to 156 patients with SSc. They were asked to
      provide their perceived difficulty in performing each manual activity on a 3
      level scale: impossible, difficult, or easy. Items were selected from well
      established psychometric criteria. The patients were reassessed 1 month later to
      test the reproducibility. Concomitantly, they were clinically evaluated for their
      disease activity/severity, and their functional ability was tested with the
      Health Assessment Questionnaire (HAQ). RESULTS: The 26 selected items defined a
      unidimensional and linear measure of manual ability and showed a continuous
      progression in their difficulty. The item difficulty hierarchy was invariant
      across 12 patient-related factors and the manual ability score was reproducible
      over time. Finally, the manual ability was significantly poorer in SSc patients
      with more severe disease, and was negatively correlated with the HAQ score (rho =
      -0.733). CONCLUSION: The SSc-adapted ABILHAND questionnaire is a reliable, valid,
      reproducible, linear, and unidimensional measure to assess and followup on the
      manual ability of patients with SSc; therefore, it could become a useful
      additional tool in clinical trials to assess treatment efficacy.

PMID- 19405013
TI  - Differences in the workforce experiences of women and men with arthritis
      disability: a population health perspective.
AB  - OBJECTIVE: To examine the employment status characteristics of people with
      arthritis disability, with a focus on gender differences and who remains in the
      workforce. METHODS: Analyses were based on cross-sectional, self-reported data of
      the Canadian Participation and Activity Limitation Survey, administered in 2001
      2002 (n = 28,908). Labor force status was categorized into employed, unemployed,
      and not in the labor force. Prevalence estimates were derived from descriptive
      analyses, and logistic regression determined the factors associated with being
      out of the labor force. Chi-square and sex-stratified analyses examined gender
      differences. RESULTS: An estimated 2.3% of the working-age population (ages 25-64
      years) reported arthritis disability, and >50% were out of the labor force. Being
      female, single, older, and having less education and more severe pain and
      disability were associated with being out of the labor force. Employed women with
      arthritis disability required more accommodations in the workplace and reported
      more activity limitations than men. Perceived discrimination was more likely to
      be reported by employed men, and men reported more changes to their work than
      women. CONCLUSION: This study underscores the importance of looking more closely
      at differences in the employment experiences of women and men. Specifically, the
      results suggest that arthritis may marginalize women and men in different ways.
      Women may be more likely to leave employment, whereas men may be more likely to
      remain working and report negative workplace experiences.

PMID- 19405014
TI  - Reintroduction of etanercept during treatment of cutaneous Mycobacterium marinum
      infection in a patient with ankylosing spondylitis.

PMID- 19405015
TI  - Circulating concentration of infliximab and response to treatment in ankylosing
      spondylitis: results from a randomized control study.
AB  - OBJECTIVE: A minority of patients with ankylosing spondylitis (AS) fail to
      respond to infliximab treatment. This study compared the circulating infliximab
      concentration and the presence of clinical symptoms in patients continuously
      treated with infliximab or after treatment interruption. METHODS: Patients with
      active AS were randomly assigned at week 0 to receive infliximab either at weeks
      4, 6, 10, and then every 6 weeks (continuous treatment), or at weeks 4, 6, and 10
      and then upon symptom recurrence (on-demand treatment). The circulating
      concentration of infliximab was determined early during treatment and at weeks 46
      and 52 for the continuous treatment group or upon relapse for the on-demand
      group. Response in the continuous treatment group was defined at week 58 using
      the ASsessment in AS International Working Group Criteria for 20% improvement.
      RESULTS: Among the 93 patients in the continuous treatment group, treatment
      failure was not associated with a low circulating concentration of infliximab,
      either during early treatment or at 1 year. Eleven (39.2%) of the 28
      nonresponders had an infliximab concentration of >10 microg/ml at week 52,
      whereas 9 (13.8%) of the 65 responders had an infliximab concentration of <1
      microg/ml. In the on-demand group, the infliximab concentration at relapse
      closely correlated with the time to relapse. However, 24 (36.9%) of 65 patients
      had a resurgence of clinical symptoms at an infliximab concentration of >10
      microg/ml, whereas 25 patients (38.4%) had a relapse at an infliximab
      concentration of <0.5 microg/ml. CONCLUSION: Responsiveness to infliximab
      treatment is highly heterogeneous among individuals with AS, and this parameter
      overcomes the circulating infliximab concentration to explain treatment success
      or failure.

PMID- 19405016
TI  - Medial opening wedge high tibial osteotomy: a prospective cohort study of gait,
      radiographic, and patient-reported outcomes.
AB  - OBJECTIVE: To evaluate the effect of medial opening wedge high tibial osteotomy
      on gait, radiographic, and patient-reported outcomes over a 2-year postoperative
      period in patients with varus alignment and medial compartment knee
      osteoarthritis, and to identify significant predictors of outcome. METHODS: We
      used an observational cohort study design and prospectively administered 3
      dimensional quantitative gait analysis, hip to ankle weight-bearing radiographs,
      and patient-reported outcomes preoperatively and 6, 12, 18, and 24 months
      postoperatively. Observed changes with 95% confidence intervals (95% CIs) were
      calculated. Multivariate linear regression and cluster analysis were used to
      evaluate associations between patient characteristics and 2-year outcomes in
      dynamic knee joint load (external knee adduction moment during gait) and Knee
      Injury and Osteoarthritis Outcome Scores (KOOS). RESULTS: A total of 126 patients
      (mean age 47.48 years) were included in the study. Mean changes suggested
      clinically important improvements in malalignment (change in mechanical axis
      angle 8.04 degrees [95% CI 7.16 degrees , 8.93 degrees ]), medial compartment
      load during gait (change in knee adduction moment -1.38 [95% CI -1.53, -1.22]
      percentage body weight x height), and all KOOS domain scores (change in pain
      23.19 [95% CI 19.49, 26.89] KOOS points). A small (13%) increase in knee
      adduction moment was observed from 6 to 24 months postoperatively. Few
      preoperative clinical and/or gait characteristics assessed at baseline were
      significantly associated with 2-year outcomes. CONCLUSION: A medial opening wedge
      high tibial osteotomy with correction to approximately neutral alignment produces
      substantial and clinically important changes in dynamic knee joint load and
      patient-reported measures of pain, function, and quality of life 2 years
      postoperatively. Changes in knee adduction moment observed in the first 2 years
      postoperatively should be explored as potential predictors of longer-term success
      and subgroups of patients with poor outcomes.

PMID- 19405017
TI  - Hip flexion range of motion and physical function in hip osteoarthritis:
      mediating effects of hip extensor strength and pain.
AB  - OBJECTIVE: Hip flexion range of motion (ROM), hip extensor strength (torque
      production), and hip pain are important correlates of physical function in
      individuals with hip osteoarthritis (OA). However, the relationships among these
      variables remain unclear. The purpose of this study was to examine whether hip
      extensor strength and hip pain mediate the association between hip flexion ROM
      and physical function. METHODS: Participants were 100 adults (mean age 62 years)
      with radiographically confirmed hip OA. Passive hip flexion ROM was measured
      using a digital inclinometer, and isometric hip extensor strength was measured
      using a force transducer. Self-report measures of physical function and pain were
      assessed by the Short Form 36 (SF-36) questionnaire, and physical performance was
      assessed by the gait speed, step test, and stair climb test. RESULTS: Multiple
      mediation analyses, adjusted for demographic and anthropometric measures,
      revealed that the association between hip flexion ROM and SF-36 physical function
      scores was fully mediated by SF-36 bodily pain scores and hip extensor strength.
      Hip extensor strength mediated the hip flexion effects on gait speed and step
      test performance, while the SF-36 bodily pain scores mediated the hip flexion
      stair performance association. CONCLUSION: In individuals with symptomatic hip
      OA, hip pain and hip extensor strength mediated the influence of hip flexion ROM
      on physical function. These results suggest that interventions to improve the
      range of hip motion may be clinically indicated.

PMID- 19405018
TI  - Patient-reported outcomes following biologic therapy in a sample of adults with
      rheumatoid arthritis recruited from community-based rheumatologists.
AB  - OBJECTIVE: To examine self-reported symptoms and functioning in a community-based
      sample of persons with rheumatoid arthritis who did and did not initiate
      treatment with biologic agents. METHODS: Data were from annual telephone
      interviews (1998-2003) with an observational cohort identified through community
      rheumatologists. Self-reported function and symptoms of subjects who initiated
      biologic therapy (etanercept or infliximab) and reported consistent use at 2
      annual interviews (continuous use; n = 64) were compared at 1 year prior to
      initiation of therapy (baseline), and years 1 and 2 of therapy to those with no
      biologic therapy (n = 183) and those who initiated biologic therapy but
      discontinued use (n = 42). RESULTS: At baseline, subjects taking biologic agents
      reported significantly worse function and symptoms on all measures except fatigue
      and pain severity. After 2 years, significant differences in the Health
      Assessment Questionnaire scores remained, but there were no other significant
      differences between the nonuser group and the continuous use group. The
      discontinued use group exhibited significantly greater pain severity and more
      painful joints than nonusers. Improvements in the number of painful (33.4% versus
      16.2%; P = 0.004), and swollen (38.4% versus 18.7%; P = 0.003) joints, and
      morning stiffness (27.3% versus 10.4%; P = 0.001) were more frequent in the
      continuous use group than in the nonuser group. CONCLUSION: Results suggest that
      biologic treatment was initiated based on severe disease. Over approximately 17
      months of treatment, differences in some but not all symptoms between the
      continuous use group and the nonuser group narrowed to statistical
      nonsignificance.

PMID- 19405019
TI  - Probing for local activity-related modulation of the infrared backscattering of
      the brain cortex.
AB  - The possibility to measure the metabolic activity of the brain cortex, with
      submillimeter spatial and subsecond temporal resolution, would open up enticing
      scenarios in addressing basic issues on the relation between different structural
      components of brain signal processing, and in providing an operational pathway to
      interaction with (dis)functional signal patterns. In the present article, we
      report the description of a simple system that allows the detection of the minute
      changes that occur in the optical backscattering of the cortex as a metabolic
      response to external stimuli. The simplicity of the system is compatible with
      scalability to an implantable probe. We validate the system on an animal model,
      and we propose an algorithm to extract meaningful data from the measured signal.
      We thus show the detection of individual haemodynamic cortical responses to
      individual stimulation events, and we provide operational considerations on the
      signal structure.

PMID- 19405020
TI  - Effects of false-evidence ploys and expert testimony on jurors' verdicts,
      recommended sentences, and perceptions of confession evidence.
AB  - During interrogations, police may use false-evidence ploys or fabricated claims
      to convince suspects to confess. Mock jurors read trial materials containing
      interrogation transcripts with or without a false-evidence ploy and one of two
      expert witness conditions (present or absent). We examined jurors' verdicts,
      recommended sentences, and perceptions of the interrogation. Although factual
      evidence and the defendant's confession remained constant across conditions,
      false-evidence ploys led to fewer convictions and shorter sentences. Jurors also
      perceived interrogations with ploys as more deceptive and coercive. Expert
      testimony reduced convictions and increased interrogation deception and coercion
      ratings. Across ploy types, participants rated demeanor ploys as less deceptive
      and recommended longer sentences for confessors. Outcomes reveal important,
      previously unrecognized consequences of false-evidence ploys.

PMID- 19405021
TI  - Studying the effects of correlation on protein selection in proteomics data.
AB  - Recently, Efron (2007) provided methods for assessing the effect of correlation
      on false discovery rate (FDR) in large-scale testing problems in the context of
      microarray data. Although FDR procedure does not require independence of the
      tests, existence of correlation grossly under- or overestimates the number of
      critical genes. Here, we briefly review Efron's method and apply it to a
      relatively smaller spectrometry proteomics data. We show that even here the
      correlation can affect the FDR values and the number of proteins declared as
      critical.

PMID- 19405022
TI  - PPI spider: a tool for the interpretation of proteomics data in the context of
      protein-protein interaction networks.
AB  - Recent advances in experimental technologies allow for the detection of a
      complete cell proteome. Proteins that are expressed at a particular cell state or
      in a particular compartment as well as proteins with differential expression
      between various cells states are commonly delivered by many proteomics studies.
      Once a list of proteins is derived, a major challenge is to interpret the
      identified set of proteins in the biological context. Protein-protein interaction
      (PPI) data represents abundant information that can be employed for this purpose.
      However, these data have not yet been fully exploited due to the absence of a
      methodological framework that can integrate this type of information. Here, we
      propose to infer a network model from an experimentally identified protein list
      based on the available information about the topology of the global PPI network.
      We propose to use a Monte Carlo simulation procedure to compute the statistical
      significance of the inferred models. The method has been implemented as a freely
      available web-based tool, PPI spider (http://mips.helmholtz
      muenchen.de/proj/ppispider). To support the practical significance of PPI spider,
      we collected several hundreds of recently published experimental proteomics
      studies that reported lists of proteins in various biological contexts. We
      reanalyzed them using PPI spider and demonstrated that in most cases PPI spider
      could provide statistically significant hypotheses that are helpful for
      understanding of the protein list.

PMID- 19405023
TI  - Detergent addition to tryptic digests and ion mobility separation prior to MS/MS
      improves peptide yield and protein identification for in situ proteomic
      investigation of frozen and formalin-fixed paraffin-embedded adenocarcinoma
      tissue sections.
AB  - The identification of proteins involved in tumour progression or which permit
      enhanced or novel therapeutic targeting is essential for cancer research. Direct
      MALDI analysis of tissue sections is rapidly demonstrating its potential for
      protein imaging and profiling in the investigation of a range of disease states
      including cancer. MALDI-mass spectrometry imaging (MALDI-MSI) has been used here
      for direct visualisation and in situ characterisation of proteins in breast
      tumour tissue section samples. Frozen MCF7 breast tumour xenograft and human
      formalin-fixed paraffin-embedded breast cancer tissue sections were used. An
      improved protocol for on-tissue trypsin digestion is described incorporating the
      use of a detergent, which increases the yield of tryptic peptides for both fresh
      frozen and formalin-fixed paraffin-embedded tumour tissue sections. A novel
      approach combining MALDI-MSI and ion mobility separation MALDI-tandem mass
      spectrometry imaging for improving the detection of low-abundance proteins that
      are difficult to detect by direct MALDI-MSI analysis is described. In situ
      protein identification was carried out directly from the tissue section by MALDI
      MSI. Numerous protein signals were detected and some proteins including histone
      H3, H4 and Grp75 that were abundant in the tumour region were identified.

PMID- 19405024
TI  - Ser/Thr/Tyr phosphoproteome analysis of pathogenic and non-pathogenic Pseudomonas
      species.
AB  - Protein phosphorylation on serine, threonine, and tyrosine is well established as
      a crucial regulatory posttranslational modification in eukaryotes. With the
      recent whole-genome sequencing projects reporting the presence of
      serine/threonine kinases and two-component proteins both in prokaryotes and
      eukaryotes, the importance of protein phosphorylation in archaea and bacteria is
      gaining acceptance. While conventional biochemical methods failed to obtain a
      snapshot of the bacterial phosphoproteomes, advances in MS methods have paved the
      way for in-depth mapping of phosphorylation sites. Here, we present
      phosphoproteomes of two ecologically diverse non-enteric Gram-negative bacteria
      captured by a nanoLC-MS-based approach combined with a novel phosphoenrichment
      method. While the phosphoproteome data from the two species are not very similar,
      the results reflect high similarity to the previously published dataset in terms
      of the pathways the phosphoproteins belong to. This study additionally provides
      evidence to prior observations that protein phosphorylation is common in
      bacteria. Notably, phosphoproteins identified in Pseudomonas aeruginosa belong to
      motility, transport, and pathogenicity pathways that are critical for survival
      and virulence. We report, for the first time, that motility regulator A, probably
      acting via the novel secondary messenger cyclic diguanylate monophosphate,
      significantly affects protein phosphorylation in Pseudomonas putida.

PMID- 19405025
TI  - Proteomic analysis of parthenogenetic and in vitro fertilized porcine embryos.
AB  - Proteomic data from embryos are essential for the completion of whole proteome
      catalog due to embryo-specific expression of certain proteins. In this study,
      using reverse phase LC-MS/MS combined with 1-D SDS-PAGE, we identified 1625
      mammalian and 735 Sus scrofa proteins from porcine zygotes that included both
      cytosolic and membranous proteins. We also found that the global protein profiles
      of parthenogenetically activated (PA) and in vitro fertilized (IVF) zygotes were
      similar but differences in expression of individual proteins were also evident.
      These differences were not due to culture conditions, polyspermy or non
      activation of oocytes, as the same culture method was used in both groups, the
      frequency of polyspermy was 24.3+/-3.0% and the rates of oocyte activation did
      not differ (p>0.05) between PA and IVF embryos. Consistent with proteomic data,
      fluorescent Hoechst 33 342 staining and terminal deoxynucleotidyl transferase
      dUTP nick end labeling assay also revealed that PA embryos were of poor quality
      as they contained less cells per blastocyst and were more predisposed to
      apoptosis (p<0.05), although their in vitro development rates were similar. To
      our knowledge, this is the first report on global peptide sequencing and
      quantification of protein in PA and IVF embryos by LC-MS/MS that may be useful as
      a reference map for future studies.

PMID- 19405026
TI  - A comprehensive proteome map of the Haemophilus parasuis serovar 5.
AB  - Haemophilus parasuis is the causative agent of Glasser's disease of pigs, a
      disease associated with fibrinous polyserositis, polyarthritis and meningitis.
      Systematic reference maps of outer membrane, intracellular and extracellular
      proteome fractions of the clinical isolate H. parasuis SH0165 were examined by 2
      DE coupled with MALDI-TOF MS. A total of 539 proteins spots were successfully
      identified, corresponding to 317 different proteins that were classified into
      functional categories. The majority of these proteins were linked to housekeeping
      functions in amino acid transport and metabolism, secondary metabolites
      biosynthesis, transport and catabolism and post-translational modification,
      protein turnover and chaperones. A significant number of outer membrane proteins
      were identified, such as Wza, Omp2, Omp5, D15 and PalA, which were supposed to
      play important roles in basic physiology of H. parasuis. In addition, several
      virulence-associated proteins involved in type I (TolC), type III (DsbA and DsbC)
      and type V (Autotransporter adhesins) secretion systems, and solute-binding
      proteins participating in iron-uptake systems were also identified in the present
      study.

PMID- 19405027
TI  - Proteomic analysis of chicory root identifies proteins typically involved in cold
      acclimation.
AB  - Chicory (Cichorium intybus) roots contain high amounts of inulin, a fructose
      polymer used as a storage carbohydrate by the plant and as a human dietary and
      prebiotic compound. We performed 2-D electrophoretic analysis of proteins from
      root material before the first freezing period. The proteins were digested with
      trypsin and the peptides analyzed by MS (MALDI-TOF/TOF). From the 881 protein
      spots analyzed, 714 proteins corresponded to a database accession, 619 of which
      were classified into functional categories. Besides expected proteins (e.g.
      related to metabolism, energy, protein synthesis, or cell structure), other well
      represented categories were proteins related to folding and stability (49 spots),
      proteolysis (49 spots), and the stress response (67 spots). The importance of
      abiotic stress response was confirmed by the observation that 7 of the 21 most
      intense protein spots are known to be involved in cold acclimation. These results
      suggest a major effect of the low temperature period that preceded root
      harvesting.

PMID- 19405028
TI  - Identification of elicitor-responsive proteins in rice leaves by a proteomic
      approach.
AB  - Experiments were conducted to identify the differentially expressed proteins in
      rice (Oryza sativa L.) plants after treatment with the glycoprotein elicitor CSB
      I, purified from ZC(13), a race of the rice blast fungus Magnaporthe grisea. The
      interactions of two near isogenic lines of rice, C101A51 and CO39, with ZC(13)
      resulted in completely incompatible and compatible types, respectively. Proteins
      were extracted from rice leaves at 12 and 24 h after treatment with CSB I.
      Temporal changes in total proteins were examined using 2-DE. Among more than 900
      protein spots reproducibly detected on each gel, 11 were up-regulated, three were
      down-regulated and seven were newly induced during, at a minimum, one time point.
      Twenty-one differentially expressed proteins were identified by linear ion trap
      quadrupole (LTQ)-MS/MS. The identified proteins were classified into six
      categories based on their putative function reported: (i) defense proteins (PR
      10a, PR-5 and putative salt-induced protein), (ii) signal transduction
      (nucleoside diphosphate kinase and putative profilin), (iii) ROS (Mn-SOD, Cu/Zn
      SOD, GST and CAT), (iv) programmed cell death (translationally controlled tumor
      protein), (v) molecule biosynthesis (putative ribosomal protein S5, putative
      ribosomal protein L12, putative translational elongation factor Tu and putative
      chaperonin 21 precursor) and (vi) metabolism (putative fructose-bisphosphate
      aldolase class-I, putative malate dehydrogenase, cytoplasmic malate
      dehydrogenase, putative acid phosphatase, putative transketolase1 and gamma
      hydroxybutyrate dehydrogenase-like protein). All of these proteins (except Cu/Zn
      SOD, putative acid phosphatase and translationally controlled tumor protein) were
      induced faster and to a higher degree in C101A51 than in CO39. These data suggest
      that the incompatible rice line may possess a more sensitive recognition system
      that can identify and react to specific chemical, biological or physical triggers
      in a more efficient manner, thus eliciting an early and fast defense response.

PMID- 19405029
TI  - Protein profile in hepatitis B virus replicating rat primary hepatocytes and
      HepG2 cells by iTRAQ-coupled 2-D LC-MS/MS analysis: Insights on liver
      angiogenesis.
AB  - Hepatitis B virus (HBV) infection and in particular Hepatitis B Virus X Protein
      have been shown to modulate angiogenesis. However, a comprehensive and
      coordinated mechanism in the HBV-induced angiogenesis remains to be established.
      In this study, transient transfection of replicative HBV genome was carried out
      in rat primary hepatocytes (RPHs) as well as HepG2 cells. Angiogenesis was
      assessed by tube formation assay. 2-D LC-MS/MS analysis was used to detect
      differentially expressed proteins in cells, supporting HBV replication compared
      with those transfected with the empty vector. A cell-based HBV replication was
      established in both RPHs and HepG2 cells. HBV replication-induced angiogenesis
      was indicated by tube formation of endothelial cells cultured in condition medium
      from RPHs or HepG2 cells supporting HBV replication. Enzymes associated with
      angiogenesis, namely fumarate hydratase and tryptophanyl-tRNA synthetase, were
      identified by 2-D LC-MS/MS analysis in HBV replicating RPHs and HepG2 cells. Our
      results indicated that the application of quantitative proteomics based on iTRAQ
      can be an effective approach to evaluate the effects of HBV replication on liver
      angiogenesis. The angiogenesis-associated proteins identified in our study may
      eventually lead to novel anti-angiogenic hepatocellular carcinoma cancer therapy
      based on tumor vascular targeting or be the markers for hepatocellular carcinoma
      diagnosis.

PMID- 19405030
TI  - Recent developments in the application of proteomics to the analysis of plant
      responses to heavy metals.
AB  - Pollution of soils by heavy metals is an ever-growing problem throughout the
      world, and is the result of human activities as well as geochemical weathering of
      rocks and other environmental causes such as volcanic eruptions, acid rain and
      continental dusts. Plants everywhere are continuously exposed to metal
      contaminated soils. The uptake of heavy metals not only constrains crop yields,
      but can also be a major hazard to the health of humans and to the entire
      ecosystem. Although analysis of gene expression at the mRNA level has enhanced
      our understanding of the response of plants to heavy metals, many questions
      regarding the functional translated portions of plant genomes under metal stress
      remain unanswered. Proteomics offers a new platform for studying complex
      biological functions involving large numbers and networks of proteins, and can
      serve as a key tool for revealing the molecular mechanisms that are involved in
      interactions between toxic metals and plant species. This review focuses on
      recent developments in the applications of proteomics to the analysis of the
      responses of plants to heavy metals; such studies provide a deeper understanding
      of protein responses and the interactions among the possible pathways that are
      involved in detoxification of toxic metals in plant cells. In addition, the
      challenges faced by proteomics in understanding the responses of plants to toxic
      metal are discussed, and some possible future strategies for meeting these
      challenges are proposed.

PMID- 19405031
TI  - Direct recognition of LPS by human but not murine CD8+ T cells via TLR4 complex.
AB  - LPS comprises a major PAMP and is a key target of the immune system during
      bacterial infection. While LPS can be recognised by innate immune cells via the
      TLR4 complex, it is unknown whether T lymphocytes, especially CD8(+) T cells are
      also capable of doing so. We report here that naive human CD8(+) T cells, after
      activation by TCR stimulation, express surface TLR4 and CD14. These activated
      CD8(+) T cells can then secrete high concentrations of IFN-gamma, granzyme and
      perforin in response to LPS. These effects can be specifically inhibited using
      siRNA for TLR4. Furthermore, LPS can synergize with IL-12 to polarize the CD8(+)
      T cells into cytotoxic T-cell 1 (Tc1) that produce IFN-gamma but not IL-4, with
      or without TCR activation. Moreover, CD8(+)CD45RO(+) memory T cells
      constitutively expressed TLR4 and markedly enhanced IFN-gamma production when
      stimulated with LPS. In contrast, activated murine CD8(+) T cells lack TLR4 and
      CD14 expression and fail to respond to LPS for proliferation and cytokine
      production. Thus, human but not murine CD8(+) T cells are able to directly
      recognise bacterial LPS via LPS receptor complex and TLR4 provides a novel signal
      for the activation of effector and memory human CD8(+) T cells.

PMID- 19405032
TI  - First evidence of a membrane-bound, tyramine and beta-phenylethylamine producing,
      tyrosine decarboxylase in Enterococcus faecalis: a two-dimensional
      electrophoresis proteomic study.
AB  - The soluble and membrane proteome of a tyramine producing Enterococcus faecalis,
      isolated from an Italian goat cheese, was investigated. A detailed analysis
      revealed that this strain also produces small amounts of beta-phenylethylamine.
      Kinetics of tyramine and beta-phenylethylamine accumulation, evaluated in
      tyrosine plus phenylalanine-enriched cultures (stimulated condition), suggest
      that the same enzyme, the tyrosine decarboxylase (TDC), catalyzes both tyrosine
      and phenylalanine decarboxylation: tyrosine was recognized as the first substrate
      and completely converted into tyramine (100% yield) while phenylalanine was
      decarboxylated to beta-phenylethylamine (10% yield) only when tyrosine was
      completely depleted. The presence of an aspecific aromatic amino acid
      decarboxylase is a common feature in eukaryotes, but in bacteria only indirect
      evidences of a phenylalanine decarboxylating TDC have been presented so far.
      Comparative proteomic investigations, performed by 2-DE and MALDI-TOF/TOF MS, on
      bacteria grown in conditions stimulating tyramine and beta-phenylethylamine
      biosynthesis and in control conditions revealed 49 differentially expressed
      proteins. Except for aromatic amino acid biosynthetic enzymes, no significant
      down-regulation of the central metabolic pathways was observed in stimulated
      conditions, suggesting that tyrosine decarboxylation does not compete with the
      other energy-supplying routes. The most interesting finding is a membrane-bound
      TDC highly over-expressed during amine production. This is the first evidence of
      a true membrane-bound TDC, longly suspected in bacteria on the basis of the gene
      sequence.

PMID- 19405033
TI  - Understanding rice plant resistance to the Brown Planthopper (Nilaparvata
      lugens): a proteomic approach.
AB  - Engineering and breeding resistant plant varieties are the most effective and
      environmentally friendly ways to control agricultural pests and improve crop
      performance. However, the mechanism of plant resistance to pests is poorly
      understood. Here we used a quantitative mass-spectrometry-based proteomic
      approach for comparative analysis of expression profiles of proteins in rice leaf
      sheaths in responses to infestation by the brown planthopper (Nilaparvata lugens
      Stal, BPH), which is a serious rice crop pest. Proteins involved in multiple
      pathways showed significant changes in expression in response to BPH feeding,
      including jasmonic acid synthesis proteins, oxidative stress response proteins,
      beta-glucanases, protein; kinases, clathrin protein, glycine cleavage system
      protein, photosynthesis proteins and aquaporins. The corresponding genes of eight
      important proteins were further analyzed by quantitative RT-PCR. Proteomic and
      transcript responses that were related to wounding, oxidative and pathogen stress
      overlapped considerably between BPH-resistant (carrying the resistance gene
      BPH15) and susceptible rice lines. In contrast, proteins and genes related to
      callose metabolism remained unchanged and glycine cleavage system protein was up
      regulated in the BPH-resistant lines, indicating that they have an efficient and
      specific defense mechanism. Our results provide new information about the
      interaction between rice and the BPH.

PMID- 19405034
TI  - RNF2 is the target for phosphorylation by the p38 MAPK and ERK signaling
      pathways.
AB  - RNF2, a member of polycomb group (PcG) proteins, is involved in chromatin
      remodeling. However, mechanisms that regulate RNF2 function are unknown. To
      identify such mechanisms, RNF2 was expressed in HEK-293 cells and analyzed by 2-D
      electrophoresis. RNF2 was resolved into at least seven protein spots, migrating
      toward the lower pI from its expected pI of 6.38, suggesting that RNF2 undergoes
      post-translational modifications. Western blotting indicated that majority of
      these RNF2 spots contained phosphoserine(s), which were completely
      dephosphorylated upon treatment with a phosphatase. SB203580, a specific
      inhibitor of p38 MAPK, inhibited RNF2 phosphorylation at one site. On the other
      hand, PD98059, an inhibitor of MEK1/2, inhibited majority of the phosphorylation
      events in RNF2. Mass spectrometry analysis identified that RNF2 expressed in Sf9
      insect cells undergoes co-translational excision of (1)Met coupled to N
      acetylation of (2)Ser, and phosphorylation of (41)Ser. Interestingly, (41)Ser is
      a predicted p38/MAPK phosphorylation site, consistent with the loss of
      phosphorylation induced by SB203580. Further analysis indicated that RNF2
      phosphorylation differentially modulates the expression of transcription factors
      and histone 2B acetylation. These results provide first evidence for
      phosphorylation of RNF2, and suggest that the mitogen activated protein kinases
      including p38 MAPK and ERK1/2 regulate growth, stress response, differentiation
      and other cellular processes, through phosphorylation of RNF2.

PMID- 19405035
TI  - High-throughput generation of tagged stable cell lines for proteomic analysis.
AB  - We present an optimized system for rapid generation of localization and affinity
      purification-tagged mammalian stable cell lines that facilitates complex
      purification and interacting protein identification. The improved components of
      this method, including the flexibility of inducible expression, circumvent issues
      associated with toxicity, clonal selection, sample yields and time to data
      acquisition. We have applied this method to the study of cell-cycle regulators
      and novel microtubule-associated proteins.

PMID- 19405036
TI  - Alford pleas in the age of innocence.
AB  - In 1970, the Supreme Court handed down a decision in North Carolina v. Alford
      that has since allowed defendants who do not wish to risk their fates at trial to
      plead guilty while simultaneously asserting their innocence. Although "Alford
      pleas" have remained unexamined by researchers, the increasing number of
      identified wrongful convictions of those factually innocent highlights the need
      for an in-depth examination of them. In the present study, using the Department
      of Justice 2004 State Survey of Inmates in Correctional Facilities dataset, we
      examined the likelihood of entering Alford pleas over traditional guilty, no
      contest, and not guilty pleas for those convicted of murder/manslaughter.
      Although we generally found few differences between the three guilty plea types,
      interesting differences between Alford and not guilty pleas emerged. Implications
      for actual innocence are discussed.

PMID- 19405037
TI  - Exposure to inhomogeneous static magnetic field ceases mechanical allodynia in
      neuropathic pain in mice.
AB  - Magnetic therapy as a self-care intervention has led to the conduct of numerous
      human trials and animal experiments. Results concerning the analgesic efficacy of
      magnetic exposure, however, are inconsistent. By using a magnetic device
      generating an inhomogeneous static magnetic field (iSMF), here we studied how the
      whole-body exposure to iSMF may influence the mechanical withdrawal threshold
      (MWT) of the hind paw in different stages of neuropathic pain evoked by partial
      ligation of the sciatic nerve in mice. It was found that iSMF exposure did not
      prevent the decrease of MWT in the first postoperative week. A 2-week long iSMF
      treatment that was started just after the nerve ligation elevated MWT values to a
      modest extent. However, the effectiveness of a daily exposure to iSMF was much
      more prominent when it was applied between postoperative days 15 and 28. In this
      case, MWT was already noticeably increased after the first treatment and it
      practically reached the control values by the end of the 2-week long exposure
      period. The results suggest that exposure to iSMF cannot prevent the development
      of mechanical allodynia, but can inhibit processes that maintain the increased
      sensitivity to mechanical stimuli in neuropathic pain.

PMID- 19405040
TI  - Daily consumption of Reliv Glucaffect for 8 weeks significantly lowered blood
      glucose and body weight in 50 subjects.
AB  - A public change to healthier lifestyles with more physical activity and better
      nutrition, including caloric restriction, is required to address the obesity
      epidemic. Weight loss can be achieved by caloric restrictions; current research
      suggests that this may be achieved by consumption of slowly absorbed
      carbohydrates owing to the resulting prolonged satiety. Our rationale was to
      prolong the satiety of overweight volunteers by supplementation with a
      proprietary formulation Glucaffect which delays absorption of carbohydrates.
      Glucaffect provides potent alpha-glucosidase inhibitors of herbal source such
      Pycnogenol, Madeglucyl and various others which obstruct absorption of
      carbohydrates, such as starch. Fifty overweight subjects received either
      Glucaffect or an inactive control product for eight weeks. Consumption of
      Glucaffect was found to statistically significantly lower blood-fasting glucose
      from baseline 145.3 mg/dL to 101.1 mg/dL (-30.4%) and Hba1c from 7.59% to 6.33%
      as compared to the control group where values decreased only marginally. The
      weight and the body mass index (BMI) decreased significantly from an average of
      88.5 kg (BMI 26.8 kg/m2) to 81.3 kg (BMI 24.5 kg/m2) as compared to the control
      group. In conclusion, Glucaffect enabled subjects with metabolic syndrome to
      achieve healthy BMI and blood glucose levels. Glucaffect was well tolerated and
      no subject dropped out.

PMID- 19405039
TI  - Independent anti-inflammatory effect of insulin in newly diagnosed type 2
      diabetes.
AB  - BACKGROUND: Although insulin has been reported to have an anti-inflammatory
      effect, whether this effect is independent of its property to reduce blood
      glucose with insulin treatment in type 2 diabetes has not been investigated in
      detail. The purpose of this study was to evaluate the independent anti
      inflammatory effect of insulin in patients with newly diagnosed type 2 diabetes.
      RESEARCH DESIGN AND METHODS: An 8-week, randomized, parallel-group study that
      enrolled 90 patients with newly diagnosed type 2 diabetes, who were randomly
      assigned to receive either insulin or metformin, was carried out. The doses of
      insulin and metformin were titrated according to fasting plasma glucose (FPG) and
      postprandial plasma glucose (PPG) during the 4 weeks; the target of FPG was 126
      mg/dL and that of PPG was 160 mg/dL. The blood glucose levels were kept
      stabilized till the end of the study. The serum concentrations of high-sensitive
      C-reactive protein (hsCRP) and interleukin (IL)-6 were measured before starting
      the study and 4 and 8 weeks after initiation of insulin or metformin therapy.
      RESULTS: After 4 weeks of dose titration, the levels of FPG were reduced in the
      two groups compared to baseline (p < 0.001), but there was no significant
      difference between the two groups (p > 0.05). During the next 4 weeks' treatment,
      the levels of FPG were stable, but the serum concentration of hsCRP and IL-6 was
      markedly reduced in the insulin-treated group compared with that in the metformin
      treated group (p < 0.001). CONCLUSIONS: Our data suggest that insulin has an anti
      inflammatory effect that is independent of the reduction it causes in blood
      glucose.

PMID- 19405041
TI  - What do potential jurors know about police interrogation techniques and false
      confessions?
AB  - Psychological police interrogation methods in America inevitably involve some
      level of pressure and persuasion to achieve their goal of eliciting confessions
      of guilt from custodial suspects. In this article, we surveyed potential jurors
      about their perceptions of a range of psychological interrogation techniques, the
      likelihood that such techniques would elicit a true confession from guilty
      suspects, and the likelihood that such techniques could elicit a false confession
      from innocent suspects. Participants recognized that these interrogation
      techniques may be psychologically coercive and may elicit true confessions, but
      believed that psychologically coercive interrogation techniques are not likely to
      elicit false confessions. The findings from this survey study indicate that
      potential jurors believe that false confessions are both counter- intuitive and
      unlikely, even in response to psychologically coercive interrogation techniques
      that have been shown to lead to false confessions from the innocent. This study
      provides empirical support for the idea that expert witnesses may helpfully
      inform jurors about the social science research on psychologically coercive
      interrogation methods and how and why such interrogation techniques can lead to
      false confessions.

PMID- 19405038
TI  - Reductions in neuronal density in elderly depressed are region specific.
AB  - OBJECTIVE: Frontal regions, including the orbitofrontal cortex (ORB) and
      dorsolateral prefrontal cortex (dlPFC) have been implicated in the neuropathology
      of geriatric depression. Prominent reductions in pyramidal neuron density have
      been recently reported in the ORB of older depressed subjects. However, the
      cellular pathology of the dlPFC has not yet been examined in these subjects.
      METHODS: Postmortem tissue from the dlPFC (Brodmann's area 9, BA9) was collected
      from 10 older (>60 years old) subjects diagnosed with major depression and 10 age
      matched non-psychiatric controls (CTRL). The majority of the subjects were the
      same as those used for our previous study on neuronal reductions in the ORB in
      older depressed. Overall (all six layers combined), and laminar density of
      pyramidal (presumably glutamatergic), and non-pyramidal (GABAergic) neurons as
      well as cortical and laminar width were measured using linear optical disector of
      Stereoinvestigator software. RESULTS: Neither the overall nor laminar density of
      pyramidal or non-pyramidal neurons was significantly different between groups.
      The cortical and laminar widths were also not affected. CONCLUSIONS: These
      results suggest that neuronal prefrontal pathology in elderly depressed is region
      specific. No significant changes were detected in the density of any type of
      neurons in the dlPFC of elderly depressed subjects (present study) whereas,
      prominent reductions in the density of pyramidal glutamatergic neurons were
      observed previously in the ORB.

PMID- 19405042
TI  - Standardization of the first-trimester fetal cardiac examination using
      spatiotemporal image correlation with tomographic ultrasound and color Doppler
      imaging.
AB  - OBJECTIVE: The challenges of the first-trimester examination of the fetal heart
      may in part be overcome by technical advances in three-dimensional (3D)
      ultrasound techniques. Our aim was to standardize the first-trimester 3D imaging
      approach to the cardiac examination to provide the most consistent and accurate
      display of anatomy. METHODS: Low-risk women with normal findings on first
      trimester screening at 11 to 13 + 6 weeks had cardiac ultrasound using the
      following sequence: (1) identification of the four-chamber view; (2) four
      dimensional (4D) volume acquisition with spatiotemporal image correlation (STIC)
      and color Doppler imaging (angle = 20 degrees, sweep 10 s); (3) offline,
      tomographic ultrasound imaging (TUI) analysis with standardized starting plane
      (four-chamber view), slice number and thickness; (4) assessment of fetal cardiac
      anatomy (four-chamber view, cardiac axis, size and symmetry, atrioventricular
      valves, great arteries and descending aorta) with and without color Doppler.
      RESULTS: 107 consecutive women (age, 16-42 years, body mass index 17.2-50.2
      kg/m(2)) were studied. A minimum of three 3D volumes were obtained for each
      patient, transabdominally in 91.6%. Fetal motion artifact required acquisition of
      more than three volumes in 20%. The median time for TUI offline analysis was 100
      (range, 60-240) s. Individual anatomic landmarks were identified in 89.7-99.1%.
      Visualization of all structures in one panel was observed in 91 patients (85%).
      CONCLUSION: Starting from a simple two-dimensional cardiac landmark-the four
      chamber view-the standardized STIC-TUI technique enables detailed segmental
      cardiac evaluation of the normal fetal heart in the first trimester.

PMID- 19405043
TI  - Inhibitory effects of a gradient static magnetic field on normal angiogenesis.
AB  - Angiogenesis, the formation of new blood vessels, is critical in many normal and
      pathological processes such as development, reproduction, tumor growth, and
      metastasis. Recently, exposure to moderate-intensity static magnetic fields (1 mT
      to 1 T) has attracted much attention for its potential therapeutic value as a
      noninvasive intervening method. Nevertheless, the effects of moderate-intensity
      and spatial gradient static magnetic fields (GSMF) on angiogenesis have not
      received enough attention. In this study, the effects of GSMF (0.2-0.4 T, 2.09
      T/m, 1-11 days) on angiogenesis were investigated both in vitro and in vivo. An
      MTT assay was used as an in vitro method to detect the proliferation ability of
      human umbilical veins endothelial cells (HUVECs). Two kinds of in vivo models, a
      chick chorioallantoic membrane (CAM) and a matrigel plug, were used to detect the
      effects of GSMF on angiogenesis. The results showed that the proliferation
      ability of HUVECs was significantly inhibited 24 h after the onset of exposure.
      With regard to the CAM model, vascular numbers in the CAM that was continuously
      exposed to the GSMF were all less than those in normal condition. In accordance
      with the gross appearance, the contents of hemoglobin in the models exposed to
      GSMF for 7-9 days were also less. In addition, similar to the CAM model, the
      results of vascular density and hemoglobin contents in the matrigel plug also
      demonstrated that the GSMF exposure for 7 or 11 days inhibited vascularization.
      These findings indicate that GSMF might inhibit or prevent new blood vessels
      formation and could be helpful for the treatment of some diseases relevant to
      pathological angiogenesis.

PMID- 19405044
TI  - Extended-release niacin decreases serum fetuin-A concentrations in individuals
      with metabolic syndrome.
AB  - BACKGROUND: Fetuin-A, a liver-secreted phosphoprotein and physiological inhibitor
      of insulin receptor tyrosine kinase, is associated with insulin resistance,
      metabolic syndrome (MetS), and an increased risk for type 2 diabetes. However,
      studies on the modulation of circulating levels of fetuin-A are limited. The goal
      of this study was to determine the effect of niacin administration on serum total
      and phosphorylated fetuin-A (phosphofetuin-A) concentrations in individuals with
      MetS and correlate with changes in serum lipids, insulin sensitivity, and markers
      of inflammation. METHODS: Fifteen sedentary, obese, male participants, who met
      the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP
      III) criteria for MetS, were treated with extended-release niacin (Niaspan) for 6
      weeks. Blood samples were obtained before and after treatment with niacin.
      RESULTS: Serum fetuin-A and phosphofetuin-A concentrations were decreased
      following niacin administration (p < 0.005). Changes in fetuin-A concentrations
      were correlated with changes in triglyceride (r = 0.62, p = 0.01) and C-reactive
      protein (CRP) concentrations (r = 0.58, p < 0.05) after niacin treatment. Changes
      in high-density lipoproteins (HDL)-cholesterol following niacin intervention were
      negatively correlated with changes in serum fetuin-A (p < 0.05) and phosphofetuin
      A concentrations (p < 0.05). Serum cortisol levels were significantly elevated
      after niacin administration. CONCLUSIONS: Niacin treatment lowers serum total-
      and phosphofetuin-A concentrations in individuals with MetS, and these changes
      correlate with the beneficial changes in serum lipids. Because niacin is known to
      induce insulin resistance, these findings suggest that fetuin-A may not be a
      mediator of niacin-induced insulin resistance but it may blunt the insulin
      resistance induced by niacin by decreasing its circulating concentrations.

PMID- 19405046
TI  - Determinants of Thailand household healthcare expenditure: the relevance of
      permanent resources and other correlates.
AB  - Several papers in the leading health economics journals modeled the determinants
      of healthcare expenditure using household survey or family budgets data of
      developed countries. Past work largely used self-reported current income as the
      core determinant, whereas the theoretically correct concept of household resource
      constraint is permanent or long-run income (a la Milton Friedman). This paper
      strives to rectify the theoretical oversight of using current income by
      augmenting the model with household asset. Using longitudinal data, we
      constructed 'wealth index' as a distinct covariate to capture the households'
      tendency to liquidate assets when defraying necessary healthcare liabilities
      after exhausting cash incomes. (Current income and assets together capture the
      household expanded resource base). Using 98 632 household observations from
      Thailand Socio-Economic Surveys (1994-2000 biennial data cycles) we found, using
      a double-hurdle model with dependent errors, that out-of-pocket healthcare
      spending behaves as a technical necessity across income quintiles and household
      sizes. Pre-1997 economic shock income elasticities are smaller than the post
      shock estimates across income quintiles for large and small households. Proximity
      to death, median age, and assets are also among other significant determinants.
      Our novel findings extend the theoretical consistency of a multi-level decision
      model in household healthcare expenditure in the developing Asian country
      context.

PMID- 19405045
TI  - When the solution is part of the problem: problem solving in elderly suicide
      attempters.
AB  - OBJECTIVES: Depression, loss, and physical illness are associated with suicide in
      the elderly. However, the nature of individual vulnerability remains poorly
      understood. Poor problem solving has been suggested as a risk factor for suicide
      in younger adults. Unresolved problems may create an accumulation of stressors.
      Thus, those with perceived deficits in problem-solving ability may be predisposed
      to suicidal behavior. To test this hypothesis, we investigated whether elderly
      suicide attempters perceived their problem solving as deficient. METHODS: Sixty
      four individuals aged 60 and older participated in the study including depressed
      suicide attempters, depressed non-attempters, and non-depressed controls. The
      social problem solving inventory-revised: short-version was used to measure
      participants' perceived social problem solving, assessing both adaptive problem
      solving dimensions (positive problem orientation and rational problem solving)
      and dysfunctional dimensions (negative problem orientation,
      impulsivity/carelessness, and avoidance). RESULTS: Depressed elderly who had
      attempted suicide perceived their overall problem solving as deficient, compared
      to non-suicidal depressed and non-depressed elderly. Suicide attempters perceived
      their problems more negatively and approached them in a more impulsive manner. On
      rational problem solving and avoidant style sub-scales, suicide attempters did
      not differ from non-suicidal depressed. However, both depressed groups reported
      lower rational problem solving and higher avoidance compared to non-depressed
      controls. CONCLUSIONS: A perception of life problems as threatening and
      unsolvable and an impulsive approach to problem solving appear to predispose
      vulnerable elderly to suicide attempts.

PMID- 19405048
TI  - Association of a new intronic polymorphism of the SOD2 gene (G1677T) with cancer.
AB  - There is growing evidence of the correlation between cancer and reactive oxygen
      species (ROS), especially superoxide. Low expression levels of the Mn-superoxide
      dismutase (SOD2) enzyme have been reported in cancer patients. Genetic variation
      in the regulatory regions of the SOD2 gene may increase the risk of cancer. We
      identified a genetic variation (G1677T, rs2Y758Y339) in the vicinity of the
      enhancer region located in intron 2 of the SOD2 gene that creates a potential
      glucocorticoid responsive element, and developed an assay to screen DNA samples
      of 220 individuals (73 control, 59 prostate cancer survival individuals and 88
      lung cancer biopsies). There were no significant differences in the genotype
      frequency distribution among prostate, lung cancer and control (p = 0.074 and
      0.057, respectively). However, we identified an association of T allele with a
      decreased risk of lung cancer (OR = 0.525, p = 0.037). The use of the G1677T
      polymorphism of SOD2 gene as a genetic risk marker may suggest new approaches for
      detection, prevention, treatment, and prognosis of cancer.

PMID- 19405049
TI  - TRPM7 is not associated with amyotrophic lateral sclerosis-parkinsonism dementia
      complex in the Kii peninsula of Japan.
AB  - Amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS/PDC) is a
      distinct neurodegenerative disorder characterized by ALS pathology with
      neurofibrillary tangles (NFTs) in the spinal cord and brain. Recent clinical
      studies have revealed a high incidence and a high familial occurrence of ALS/PDC
      in both Guam and the Kii peninsula of Japan, suggesting a strong genetic
      predisposition to this disorder. The T1482I variant (rs8042919) of TRPM7 gene
      which is suggested to play roles in regulating the cellular homeostasis of
      Ca(2+), Mg(2+), and trace metals, has recently been reported to be associated
      with Guamanian patients with ALS/PDC. To investigate whether TRPM7 is associated
      with Kii ALS/PDC, we conducted parametric linkage analyses of the TRPM7 locus in
      a large extended family with ALS/PDC. Linkage analysis did not reveal any
      evidence supporting the linkage to the TRPM7 locus. Resequencing of the entire
      coding region of TRPM7 did not reveal any pathogenic mutations in an affected
      individual in this family. The allele frequencies of the T1482I in affected
      individuals in this family or in those from other families are not significantly
      different from those in regional controls or those in HapMap-JPT samples. These
      results indicate that TRPM7 is not associated with ALS/PDC in the Kii peninsula
      of Japan.

PMID- 19405050
TI  - Characterization of pharmacogenetically relevant CYP2D6 and ABCB1 gene
      polymorphisms in a Portuguese population sample.
AB  - Differences in metabolism of drugs can lead to severe toxicity or therapeutic
      failure. In addition to cytochrome P450 2D6, which plays a critical role in drug
      metabolism, ABCB1 encoded P-glycoprotein (PGP) is also an important determinant
      in drug bioavailability. The genes encoding these molecules are highly variable
      among populations and, given their clinical importance in drug therapy,
      determining CYP2D6 and ABCB1 allele frequencies in specific populations is very
      important for useful application in clinical settings. In this study the
      frequency of the pharmacologically relevant CYP2D6*3, *4, *5, *6 allelic variants
      and gene duplication, and ABCB1 C1236T and C3435T gene polymorphisms and their
      haplotypes was determined in a population sample of 100 Portuguese healthy
      subjects. CYP2D6 allele frequencies were 1.4% (*3), 13.3% (*4), 2.8% (*5), 1.8%
      (*6) and 6.1% (gene duplication), with 5% of the individuals classified as PM and
      8.4% as UM. The frequencies obtained for the non-functional alleles and for the
      CYP2D6 gene duplication are in agreement with other South European populations,
      and reinforce the previously suggested south/north gradient of CYP2D6
      duplications. Allelic frequencies for the ABCB1 polymorphisms were 52% (3435C)
      and 54% (1236C) and the most common haplotype (1236C-3435C) occurred with a
      frequency of 45.5%. Although allele and haplotype frequency data for ABCB1 in
      Southern Europe is limited, some discrepancies were found with other European
      populations, with possible therapeutic implications for PGP substrate drugs.

PMID- 19405051
TI  - Quenching mechanisms and diffusional pathways in micellar systems unravelled by
      time-resolved magnetic-field effects.
AB  - Magnetic-field effects (MFEs) are used to investigate the photoreaction of
      xanthone (A) and DABCO (D) in anionic (SDS) or cationic (DTAC) micelles at high
      pH (DABCO = 1,4-diazabicyclo[2.2.2]octane, SDS = sodium dodecyl sulfate, DTAC =
      dodecyl trimethyl ammonium chloride). From MFE experiments with nanosecond time
      resolution, the radical anion A(.)(-) can be observed without any interference
      from the much more strongly absorbing triplet (3)A*, the different quenching
      processes can be separated and their rates can be measured. Triplet (3)A* is
      quenched dynamically both by the SDS micelle (k(1) = 5.0x10(5) s(-1)) and by
      DABCO approaching from the aqueous phase (k(2) = 2.0x10(9) M(-1) s(-1)). Static
      quenching by solubilised DABCO (association constant with the SDS micelles, 1.5
      M(-1)) also participates at high DABCO concentrations, but is chemically
      nonproductive and does not lead to MFE generation. The MFEs stemming from the
      radical ion pairs A(.)(-) D(.)(+) are about 40 times larger in the anionic
      micelles than in the cationic ones despite a higher yield of free radicals in the
      latter case. This can be rationalised by different diffusional dynamics: Because
      of the location of their precursors, A(.)(-) and D(.)(+) are formed at opposite
      sides of the micelle boundary. Subsequently, the negatively charged Stern layer
      of the SDS micelle traps the radical cation, which then undergoes surface
      diffusion, so both the recombination probability and the spin mixing are high; in
      contrast, the positive surface charge of the DTAC micelle forces the radical
      cation into the bulk of the solution, thus efficiently blocking a recombination.

PMID- 19405052
TI  - Catalytic asymmetric Baeyer-Villiger oxidation in water by using Pt(II) catalysts
      and hydrogen peroxide: supramolecular control of enantioselectivity.
AB  - The enantioselective Baeyer-Villiger oxidation of cyclic ketones is a challenging
      reaction, especially when using environmentally friendly oxidants. The reaction
      was carried out in water by using soft Lewis acid Pt(II) complexes that have
      chiral diphosphines as well as monophosphines. Addition of a surfactant is
      crucial, which leads to the formation of micelles that act as nanoreactors in
      which the substrate and catalyst encounter each other in an ordered medium that
      in several cases positively influences both the conversion and the selectivity of
      the reactions. This is due to the combination of the hydrophobic effect (which
      confines the components of the reaction in the micelles), together with
      supramolecular interactions between the partners within the ordered palisade
      provided by the alkyl chains of the surfactant. For the oxidation of meso
      cyclobutanones, addition of surfactant allowed the reaction to proceed in high
      yields and the enantiometic excess (ee; 56%) was higher than in organic solvents.
      Subsequent extension to meso-cyclohexanones resulted in a general decrease in
      yields but an enhancement of enantioselectivity (ee up to 92%) moving from
      organic to water-surfactant media, regardless of the substrate or the catalyst
      employed. Different behaviour was observed with chiral cyclobutanones 7 and 10:
      with 7 the best catalyst was 1 g, whereas with the larger substrate, 10,
      complexes 1 a-b performed better in terms of enantioselectivity. Each combination
      of substrate, catalyst and surfactant is a new system and supramolecular
      reciprocal interactions together with the hydrophobic character of the
      counterparts play crucial roles. The asymmetric Baeyer-Villiger oxidation in
      water catalyzed by 1 a-h in the presence of micelles is a viable reaction that
      often benefits from the hydrophobic effect, leading to substantial increases in
      enantioselectivity.

PMID- 19405053
TI  - Highly enantio- and diastereoselective organocatalytic desymmetrization of
      prochiral cyclohexanones by simple direct aldol reaction catalyzed by proline.

PMID- 19405054
TI  - Red- and blue-shifted hydrogen bonds in the cis-trans noncyclic formic acid
      dimer.
AB  - The cis-trans noncyclic formic acid dimer was studied by means of MP2 method with
      6-31G(d,p), 6-31+G(d,p) and 6-311+G(d,p) basis sets. It exhibits simultaneously
      red-shifted O-H...O and blue-shifted C-H...O hydrogen bonds. AIM and NBO analyses
      are performed at the MP2/6-31+G(d,p) level to explore their properties and
      origins. AIM analysis provides the evidence that the O-H bond becomes weaker and
      the C-H bond becomes stronger upon the hydrogen bond formations. Intermolecular
      and intramolecular hyperconjugations have important influence on the electron
      densities in the X-H (X = O, C) sigma bonding orbital and its sigma* antibonding
      orbital. The electron densities in the two orbitals are closely connected with
      the X-H (X = O, C) bond length, and they are used to quantitatively estimate the
      bond length variation. The larger amount of charge transfer in the red-shifted O
      H...O hydrogen bond is due to its favorable H...O electron channel, whereas the
      H...O electron channel in the blue-shifted C-H...O hydrogen bond is weaker.
      Structural reorganization effects shorten the C-H bond by approximately 30% when
      compared to the C-H bond contraction upon the dimerization. Strikingly, it leads
      to a small elongation and a slight red shift of the O-H bond. Both
      rehybridization and repolarization result in the X-H (X = O, C) bond contraction,
      but their effects on the O-H bond do not hold a dominant position. The hydrogen
      bonding processes go through the electrostatic attractions, van der Waals
      interactions, charge-transfer interactions, hydrogen-bonding interactions and
      electrostatic repulsions. Electrostatic attractions are of great importance on
      the origin of the red-shifted O-H...O hydrogen bond, especially the strong
      H(delta+)...O(delta-) attraction. For the blue-shifted C-H...O hydrogen bond, the
      considerable nucleus-nucleus repulsion between H and O atoms caused by the strong
      electrostatic attraction between C and O atoms is a possible reason for the C-H
      bond contraction and its blue shift.

PMID- 19405055
TI  - Conformational landscape of supersonically expanded 1-(fluorophenyl)ethanols and
      their monohydrated clusters.
AB  - The effects of the presence of the ring fluorine atom on the conformational
      landscape of supersonically expanded isomeric 1-(fluorophenyl)ethanols and their
      monohydrated clusters are investigated by resonant two-photon ionization (R2PI)
      spectroscopy, coupled with time-of-flight (TOF) mass spectrometry. In contrast to
      the very simple spectrum of 1-phenylethanol, the lack of structural symmetry of
      the aromatic rings of isomeric 1-(fluorophenyl)ethanols generates more
      complicated spectra, characterized by several low-frequency progressions of
      bands. Their interpretation is based on the strict correspondence with
      theoretical predictions at the D-B3LYP/6-31G** level of theory. Monohydration of
      the 1-(fluorophenyl)ethanol isomers favours exclusive formation of the
      corresponding conformers, characterized by the O-H...O(w)-H...pi intracomplex
      interaction and whose excitation spectrum exhibits features attributed to the
      C(1)-C(alpha) torsion plus intermolecular water torsion.

PMID- 19405056
TI  - The folly of protobranching: turning repulsive interactions into attractive ones
      and rewriting the strain/stabilization energies of organic chemistry.
AB  - Strain/stabilization energies: Recently it has been argued that the accepted
      strain/stabilization energies of fundamental species are incorrect because they
      ignore the effects of protobranching. Here it is shown that the basic premise of
      the protobranching mechanism is unlikely and that conventional
      strain/stabilization energies are more chemically important than those from the
      protobranching approach.

PMID- 19405057
TI  - Cage chirality of P-C cage compounds: highly diastereoselective formation of
      diastereomeric P5-deltacyclenes, separation of diastereomers, and removal of the
      chiral auxiliary.
AB  - An effective cyclic addition reaction of diastereomeric (R*)diphenyltin-3,5
      di(tert-butyl)-1,2,4-triphosphole derivatives 6 a-c (R* = (-)-cis-myrtanyl (a), (
      )-trans-myrtanyl (b), m-(2-bornyl-2-ene)phenyl (c) with two equivalents of tert
      butylphosphaalkyne 1 leads to 1:1 mixtures of diastereomeric stannylated
      pentaphosphadeltacyclene derivatives 7 a-c with seven stereogenic centers in the
      cage unit. The (-)-cis-myrtanyl derivative 7 a could be separated into its
      diastereomers; destannylation of diastereomer 7 a(RR) led to the P-H cage 8 as a
      pure enantiomer. Circular dichroism (CD) spectroscopy of the pure diastereomer 7
      a(RR) and the enantiomer 8 give evidence for identical stereoisomers of the P(5)
      deltacyclene cage units and prove a strong dominance of the chiral cages over the
      chiral auxiliary groups with respect to their chiroptical properties. Absolute X
      ray structure investigations of the majority of the compounds presented in the
      paper reveal the details of the stereochemistry of the asymmetric P-C cage units.
      In this paper we demonstrated for the first time a general preparative route to
      stereochemically fully defined asymmetric P-C cage compounds by separation of
      diastereomers and replacement of the chiral auxiliary group.

PMID- 19405058
TI  - Predicting the NMR spectra of paramagnetic molecules by DFT: application to
      organic free radicals and transition-metal complexes.
AB  - Nuclear shieldings, including the Fermi contact and pseudocontact terms, have
      been calculated with DFT methods in a variety of open-shell molecules
      (nitroxides, aryloxyl and various transition-metal complexes), thereby predicting
      (1)H and (13)C chemical shifts. In general, when experimental data are reliable a
      good agreement with experimental values is observed, thus demonstrating the
      predictive power of DFT also in this context. However, the general accuracy is
      lower than that for closed-shell species. A few inconsistencies in literature
      values are reconciled by reassigning some shifts. Structural, magnetic, and
      dynamic parameters have also been put into the Solomon-Bloembergen equations to
      predict signal line shapes, in particular those of signals that are difficult to
      locate or are undetectable. Guidelines are provided to predict the order of
      magnitude of relaxation rates. It is shown that DFT-predicted paramagnetic shifts
      can greatly assist in obtaining and understanding the NMR spectra of paramagnetic
      molecules, which generally require different experimental strategies and exhibit
      problems in detection and assignment.

PMID- 19405059
TI  - Highly selective catalytic conversion of phenolic bio-oil to alkanes.
AB  - Oil and water: A new energy-efficient and atom-economical catalytic route for the
      production of alkanes and methanol by upgrading the phenolic fraction of bio-oil
      has been developed. The one-pot aqueous-phase hydrodeoxygenation process is based
      on two catalysts facilitating consecutive hydrogenation, hydrolysis, and
      dehydration reactions.

PMID- 19405060
TI  - Understanding covalent mechanochemistry.
AB  - The time is ripe: A general theoretical framework based on force-transformed
      potential energy surfaces rationalizes the intriguing results of recent
      experiments in the emerging field of covalent mechanochemistry.

PMID- 19405061
TI  - Structural tracking of a bimolecular reaction in solution by time-resolved X-ray
      scattering.
AB  - Molecular movies: Time-resolved X-ray scattering provides direct structural
      information on an electronically excited complex while it is formed in the
      bimolecular reaction between excited octahydrogen[tetrakis-mu-diphosphito
      1kappaP:2kappaP'-diplatinate](4-) (PtPOP*) and thallium ions. In the exciplex one
      thallium(I) and two platinum(II) ions are found to be collinear.

PMID- 19405062
TI  - Raman spectra of poly(p-phenylenevinylene)s with fluorinated vinylene units:
      evidence of inter-ring distortion.
AB  - Ring the changes: Experimental Raman spectra of fluorinated and non-fluorinated
      polyphenylenevinylenes are assigned according to quantum chemical calculations
      for oligomer model systems [picture: see text]. Characteristic differences in the
      spectra can be traced back to strong inter-ring distortion of the fluorinated
      compounds.The Raman spectrum of poly{2-methoxy-5-[(2-ethylhexyl)oxy]-1,4
      phenylenedifluorovinylene} (MEH-PPDFV) is reported and compared with that of a
      well-known non-fluorinated reference polymer, namely poly{2-methoxy-5-[(2
      ethylhexyl)oxy]-1,4-phenylenevinylene} (MEH-PPV). The Raman spectra of both
      polymers are assigned on the basis of density functional theory calculations of
      the corresponding oligomers. The main differences between vinylene fluorinated
      and non-fluorinated structures deal with the intensity, frequency shift and
      broadening of C--C vinylene stretching. Additional differences concern the
      relative intensities of C-C phenylene and vinylene stretching as well as the
      deformation modes in the range 1250-1350 cm(-1). It is shown that these effects
      are due to the larger distortion from planarity of the fluorinated polymer,
      compared with the non-fluorinated counterpart, induced by repulsive interactions
      between the fluorine atoms on the vinylene units and the oxygen atoms of the
      alkoxy groups on the aromatic rings.

PMID- 19405063
TI  - Further evidence of the anti-inflammatory effects of silver nanoparticles.
AB  - The production of pure silver in nanoparticle size has opened new dimensions in
      the clinical use of this precious metal. We and others have demonstrated
      previously that silver nanoparticles (nAg) possess efficient antimicrobial
      activity. Herein we show they may also have significant anti-inflammatory effects
      in a postoperative peritoneal adhesion model. This finding provides further
      insight into the biological actions of nAg as well as a potentially novel therapy
      for peritoneal adhesions in clinical surgery.With the advent of nanoscience, pure
      silver can now be made into nanometer-sized particles. As a result, we are able
      to explore the potentially beneficial properties of pure silver. In our previous
      study using a burn wound model in mice, we demonstrated that besides
      antibacterial action, silver nanoparticles (nAg) appear to have anti-inflammatory
      properties. Herein we further confirm the anti-inflammatory effects of nAg and
      explore their potential clinical application through a postoperative peritoneal
      adhesion model. We also elucidate the potential mechanism of action of silver.
      Our in vitro and in vivo experimental findings show that nAg are effective at
      decreasing inflammation in peritoneal adhesions without significant toxic
      effects. This study thus provides further evidence for and contributes to the
      understanding of the anti-inflammatory properties of nAg and may also give a
      novel therapeutic direction for the prevention of postoperative adhesions.

PMID- 19405064
TI  - Discovery of a new class of non-imidazole oxazoline-based histamine H(3) receptor
      (H(3)R) inverse agonists.
AB  - H(3)R inverse agonists based on an aminopropoxy-phenyloxazoline framework
      constitute highly valuable druglike lead compounds that display efficacy in a
      mouse model of recognition memory.

PMID- 19405065
TI  - Parallel pathways and free-energy landscapes for enzymatic hydride transfer
      probed by hydrostatic pressure.
AB  - Mutation of an active-site residue in morphinone reductase leads to a
      conformationally rich landscape that enhances the rate of hydride transfer from
      NADH to FMN at standard pressure (1 bar). Increasing the pressure causes
      interconversion between different conformational substates in the mutant enzyme.
      While high pressure reduces the donor-acceptor distance in the wild-type enzyme,
      increased conformational freedom "dampens" its effect in the mutant.We show that
      hydride transfer from NADH to FMN catalysed by the N189A mutant of morphinone
      reductase occurs along parallel "chemical" pathways in a conformationally rich
      free-energy landscape. We have developed experimental kinetic and spectroscopic
      tools by using hydrostatic pressure to explore this free-energy landscape. The
      crystal structure of the N189A mutant enzyme in complex with the unreactive
      coenzyme analogue NADH(4) indicates that the nicotinamide moiety of the analogue
      is conformationally less restrained than the corresponding structure of the wild
      type NADH(4) complex. This increased degree of conformational freedom in the
      N189A enzyme gives rise to the concept of multiple reactive configurations
      (MRCs), and we show that the relative population of these states across the free
      energy landscape can be perturbed experimentally as a function of pressure.
      Specifically, the amplitudes of individual kinetic phases that were observed in
      stopped-flow studies of the hydride transfer reaction are sensitive to pressure;
      this indicates that pressure drives an altered distribution across the energy
      landscape. We show by absorbance spectroscopy that the loss of charge-transfer
      character of the enzyme-coenzyme complex is attributed to the altered population
      of MRCs on the landscape. The existence of a conformationally rich landscape in
      the N189A mutant is supported by molecular dynamics simulations at low and high
      pressure. The work provides firm experimental and computational support for the
      existence of parallel pathways arising from multiple conformational states of the
      enzyme-coenzyme complex. Hydrostatic pressure is a powerful and general probe of
      multidimensional energy landscapes that can be used to analyse experimentally
      parallel pathways for enzyme-catalysed reactions. We suggest that this is
      especially the case following directed mutation of a protein, which can lead to
      increased population of reactant states that are essentially inaccessible in the
      free-energy landscape of wild-type enzyme.

PMID- 19405066
TI  - Probing the role of backbone hydrogen bonding in a critical beta sheet of the
      extracellular domain of a cys-loop receptor.
AB  - Probing the sheet: The network of hydrogen bonds formed in the outer beta sheet
      of the nicotinic acetylcholine receptor (nAChR; see figure) is fairly robust and
      tolerates single amide-to-ester mutations throughout. However, eliminating two
      proximal hydrogen bonds completely destroys receptor function; this adds further
      support to gating models that ascribe important roles to these beta strands of
      the nAChR extracellular domain.Long-range communication is essential for the
      function of members of the Cys-loop family of neurotransmitter-gated ion
      channels. The involvement of the peptide backbone in binding-induced
      conformational changes that lead to channel gating in these membrane proteins is
      an interesting, but unresolved issue. To probe the role of the peptide backbone,
      we incorporated a series of alpha-hydroxy acid analogues into the beta-sheet-rich
      extracellular domain of the muscle subtype of the nicotinic acetylcholine
      receptor, the prototypical Cys-loop receptor. Specifically, mutations were made
      in beta strands 7 and 10 of the alpha subunit. A number of single backbone
      mutations in this region were well tolerated. However, simultaneous introduction
      of two proximal backbone mutations led to surface-expressed, nonfunctional
      receptors. Together, these data suggest that while the receptor is remarkably
      robust in its ability to tolerate single amide-to-ester mutations throughout
      these beta strands, more substantial perturbations to this region have a profound
      effect on the protein. These results support a model in which backbone movements
      in the outer beta sheet are important for receptor function.

PMID- 19405067
TI  - Solution-based evolution and enhanced methanol oxidation activity of monodisperse
      platinum-copper nanocubes.
AB  - Shape-controlled catalysis: High-quality Pt-Cu nanocubes with an average size of
      about 8 nm (see picture, scale bar = 20 nm) were synthesized from a high
      temperature organic solution system in the presence of various capping ligands.
      These cubic Pt-Cu nanocrystals terminated with {100} facets demonstrated a
      superior catalytic activity towards methanol oxidation compared to similar sized
      Pt-Cu and Pt nanospheres.

PMID- 19405068
TI  - Histone H3 N-terminal peptide binds directly to its own mRNA: a possible mode of
      feedback inhibition to control translation.
AB  - Give me some feedback: In vitro selection of aptamers against the H3 peptide
      provided specific hairpin RNAs that possess high homology with histone H3 mRNA.
      The identified H3 hairpin RNA binds specifically to the H3 peptide with
      micromolar affinity and dose-dependently inhibits in vitro translation of the H3
      protein. Consequently, the hairpin RNA and H3 peptide are one of the rare cis-
      and trans-elements on coding regions found among housekeeping proteins in higher
      eukaryotes.

PMID- 19405069
TI  - A hydride-rich magnesium cluster.
AB  - High-de-hydride! A straightforward reaction between a magnesium silylamido/N
      heterocyclic carbene adduct and phenylsilane provides a {Mg(4)H(6)} cluster
      molecule that may be regarded as a combination of two magnesium dihydride and two
      magnesium monohydride moieties.

PMID- 19405071
TI  - Enantioselective Robinson-type annulation reaction catalyzed by chiral phosphoric
      acids.
AB  - Let's resolve our differences: Implementation of an enantioselective Michael
      addition followed by an intramolecular aldol reaction catalyzed by two phosphoric
      acids has enabled the synthesis of cyclohexenone derivatives with excellent
      enantioselectivities. Prominent kinetic resolution was observed in the latter
      reaction. Ar = aromatic group, X = H, halogen, Y = H, Me, halogen.

PMID- 19405078
TI  - Current literature in diabetes.

PMID- 19405074
TI  - Design of triazole-tethered glycoclusters exhibiting three different spatial
      arrangements and comparative study of their affinities towards PA-IL and RCA 120
      by using a dna-based glycoarray.
AB  - Sugar-coated chips: Glycoside clusters are valuable tools for carbohydrate-lectin
      recognition studies. However, the spatial arrangement of the sugar residues is a
      key issue in the design of high-affinity glycoclusters. Here the affinities of
      linear and antenna- and calixarene-based galactoside clusters towards two lectins
      derived from Pseudomonas aeruginosa and Ricinus communis were compared by means
      of glycoarrays.Interactions between proteins and carbohydrates are involved in a
      large number of crucial biological events. Many efforts have been devoted to the
      design and synthesis of unnatural saccharides displaying high affinities towards
      targeted lectins. Among others, glycoside clusters have proven to be valuable
      tools for these recognition studies. However, the spatial arrangements of the
      sugar residues are a key issue in the design of high-affinity glycoclusters.
      Here, the affinities of linear and antenna- and calixarene-based galactoside
      clusters against two lectins, derived from Pseudomonas aeruginosa and Ricinus
      communis, have been compared by means of glycoarrays.

PMID- 19405075
TI  - Advanced glycation end products in diabetic patients with optimized glycaemic
      control and their effects on endothelial reactivity: possible implications in
      venous graft failure.
AB  - BACKGROUND: Diabetic patients exhibit an increased risk of saphenous graft
      occlusion after coronary bypass. Advanced glycation end products (AGEs) are
      ubiquitous signalling proteins that are associated with vascular and neurological
      complication of diabetes. The aim of this study is to verify whether AGE levels
      may promote endothelial cell alterations responsible for vein graft failure.
      METHODS: Segments of saphenous vein were obtained from both normal people and
      diabetic patients (HbA(1c) < 6.0%) at the time of coronary surgery. Cultured
      endothelial cells were incubated in the absence/presence of AGEs (2 and 20
      microM), and mRNA and protein for both receptor of AGEs (RAGE) and peroxisome
      proliferator-activated receptors-gamma (PPAR-gamma) were analysed by real-time
      polymerised chain reaction (PCR) and Western blot analysis. In the same fashion,
      the cell release of reactive oxygen species (ROS) was estimated in the
      absence/presence of AGEs by spectrofluorimetric analysis. Finally, neutrophil
      endothelial adhesion was evaluated in saphenous vein segments with and without
      the addition of AGEs. RESULTS: AGEs activated in a dose-dependent manner the
      expression of RAGE and inhibited PPAR-gamma expression in endothelial cells as
      testified by both reverse transcription-PCR (RT-PCR) and Western blot analysis.
      Stimulation of cultured endothelial cells with AGEs significantly enhanced
      intracellular ROS formation in a dose-dependent manner. Finally, neutrophil
      endothelial adhesion was significantly increased after incubation of control
      veins with AGEs. CONCLUSIONS: These findings indicate that even in diabetic
      patients with HbA(1c) < 6.0%, elevated serum levels of AGE determine a sort of a
      pro-thrombotic state, providing a common mechanism that could explain the
      increased rate of vein graft occlusion in this population.

PMID- 19405079
TI  - New prospects for immunotherapy at diagnosis of type 1 diabetes.
AB  - Immune intervention at diagnosis of type 1 diabetes (T1D) aims to prevent or
      reverse the disease by blocking autoimmunity, thereby preserving/restoring beta
      cell mass and function. Recent clinical trials of non-specific and of antigen
      specific immune therapies have demonstrated the feasibility of modulation of
      islet-specific autoimmunity in patients with partial prevention of loss of
      insulin secretion. In a series of review articles published in this issue of the
      journal, some of the most promising approaches of immune intervention in T1D are
      presented. Here we outline the rationale of such interventions and future
      prospects in this area.

PMID- 19405080
TI  - The prevalence of GAD antibodies in Korean women with gestational diabetes
      mellitus and their clinical characteristics during and after pregnancy.
AB  - BACKGROUND: We conducted this research in order to evaluate the prevalence of
      glutamic acid decarboxylase antibodies (GADA) in Korean women with gestational
      diabetes mellitus (GDM), to identify the clinical characteristics of these women,
      and to gauge the prevalence of diabetes among them after childbirth. METHODS: We
      studied 887 Korean women with GDM who were screened for GADA, and assessed their
      antepartum clinical characteristics and the outcomes of their pregnancies. At 6
      weeks' postpartum, 75 g oral glucose tolerance tests were performed to determine
      the diabetic status of GDM women with GADA. RESULTS: The prevalence of GADA in
      Korean women with GDM was 1.7%. Plasma glucose levels at 0- and 3-h during oral
      glucose tolerance tests were significantly different between GADA-positive and
      GADA-negative women with GDM. There were no significant differences between them
      in terms of age, body mass index, family history of diabetes, fasting insulin,
      and lipid profiles. However, GADA-positive women with GDM required insulin
      treatment during pregnancy more frequently than GADA-negative patients. The
      development of diabetes at early postpartum was significantly higher in GADA
      positive women with GDM than those who were GADA negative. CONCLUSIONS: The
      prevalence of GADA in Korean women with GDM was low. However, GADA-positive women
      with GDM are more susceptible to subsequently developing type 1 diabetes, even in
      the early postpartum period. Long-term follow up studies and intervention to
      prevent type 1 diabetes among GADA-positive GDM women are needed.

PMID- 19405081
TI  - The anti-interleukin-1 in type 1 diabetes action trial--background and rationale.
AB  - Type 1 diabetes (T1D) is caused by an inflammatory destruction of pancreatic beta
      cells. Pro-inflammatory cytokines, in particular interleukin-1 (IL-1), have been
      suggested to be effector molecules based on the observations that pro
      inflammatory cytokines cause beta-cell apoptosis in vitro and aggravate diabetes
      in vivo, and that inhibition of the action of these cytokines reduce diabetes
      incidence in animal models of type 1 diabetes and islet graft destruction. This
      review presents the rationale for and design of a recently launched double-blind,
      multicenter, randomized clinical trial that investigates the effect of
      interleukin-1 antagonism on beta-cell function in subjects with T1D of recent
      onset.

PMID- 19405083
TI  - The physical characteristics and usage patterns of stone axe and pounding hammers
      used by long-tailed macaques in the Andaman Sea region of Thailand.
AB  - Stone hammering in natural conditions has been extensively investigated in
      chimpanzees and bearded capuchins. In contrast, knowledge of stone tool use in
      wild Old World monkeys has been limited to anecdotal reports, despite having
      known for over 120 years that Macaca fascicularis aurea use stone tools to
      process shelled foods from intertidal zones on islands in the Andaman Sea. Our
      report is the first scientific investigation to look at the stone tools used by
      these macaques. We observed they were skilled tool users and used stone tools
      daily. They selected tools with differing qualities for differing food items, and
      appeared to use at least two types of stone tools. Pounding hammers were used to
      crush shellfish and nuts on anvils and axe hammers were used to pick or chip at
      oysters attached to boulders or trees. We found significant physical differences
      between these two tools. Tools at oyster beds were smaller and exhibited scarring
      patterns focused more often on the points, whereas tools found at anvils were
      larger and showed more scarring on the broader surfaces. We also observed grip
      differences between the two tool types. Lastly, macaques struck targets with axe
      hammers more rapidly and over a wider range of motion than with pounding hammers.
      Both our behavioral and lithic data support that axe hammers might be used with
      greater control and precision than pounding hammers. Hand-sized axe hammers were
      used for controlled chipping to crack attached oysters, and larger pounding
      hammers were used to crush nuts and unattached shellfish on anvils. In addition
      to stones, they also used hand-sized auger shells (Turritella attenuata) as picks
      to axe attached oysters. Pound hammering appears similar to the stone tools used
      by chimpanzees and capuchins, but axe hammering has not yet been documented in
      other nonhuman primates in natural conditions.

PMID- 19405082
TI  - Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic
      mice islets.
AB  - BACKGROUND: Taurine (TAU), a naturally occurring sulfur-containing amino acid, is
      found at high concentrations in plasma and mammalian tissues and regulates
      osmolarity, ion channel activity, and glucose homeostasis. Several reports have
      shown that physiological plasma TAU levels seem to be important for adequate beta
      (beta)-cell function and insulin action, since low concentrations of TAU in the
      plasma have been reported in the pre-diabetic and diabetic states. METHODS:
      Glucose tolerance and insulin sensitivity were investigated in mice supplemented
      with 2% (w/v) TAU in their drinking water for 30 days, as well as the insulin
      secretion from isolated islets stimulated by glucose or L-leucine. RESULTS: TAU
      supplemented mice demonstrated improved glucose tolerance and higher insulin
      sensitivity, compared to controls (CTL). In addition, their islets secreted more
      insulin in response to high concentrations of glucose and L-leucine. L-[U
      (14)C]leucine oxidation was higher in TAU than in CTL islets, whereas D-[U
      (14)C]glucose oxidation, ATP levels, glucose transporter (GLUT) 2 and glucokinase
      (GCK) protein expressions were similar in both types of islets. The L-type
      beta(2) subunit voltage-sensitive Ca(2+) channel protein, as well as (45)Ca
      uptake, were significantly higher in TAU-supplemented than CTL islets. In
      addition, islets from TAU-supplemented mice secreted more glucagon than CTL
      islets at low glucose. CONCLUSIONS: TAU supplementation improves glucose
      tolerance and insulin sensitivity in mice, as well as insulin secretion from
      isolated islets. The latter effect seems to be, at least in part, dependent on a
      better Ca(2+) handling by the islets.

PMID- 19405084
TI  - Novel three-dimensional MRI technique for study of cartilaginous hip surfaces in
      Legg-Calve-Perthes disease.
AB  - Treatment of Legg-Calve-Perthes disease (LCPD) may improve if new knowledge can
      be obtained regarding how articular cartilage changes shape during the course of
      this disorder. A new technique is presented showing how analyses of magnetic
      resonance images can be used to quantify the three-dimensional changes in the
      femoral and acetabular articulating cartilage surfaces of children with LCPD. Ten
      male subjects (8 +/- 1 years) with unilateral LCPD were enrolled in this IRB
      approved study. Sets of magnetic resonance images of both hips were obtained at
      three different times. Three-dimensional virtual models of the cartilage were
      created from these images, and mathematical spheres were fit to the articulating
      surfaces. Five parameters (size, shape deformity (sphericity error), radial
      growth rate, joint fit, and joint incongruity) were used to quantify cartilage
      surface shape. Data were analyzed by using a linear mixed-model. Joint
      incongruity, i.e., the distance between the centers of the femoral and acetabular
      spheres, was slightly more than 2.5 times larger (p = 0.001) in LCPD hips than
      the contralateral normal hips. Cartilage shape deformity was 65% larger in hips
      with LCPD than in normal hips. Growth rates of the femoral head and the opposing
      acetabular surface showed that distortion of the femoral surface occurred first
      and the opposing acetabular surface followed. Mean radial difference (acetabular
      surface radius minus femoral surface radius) in LCPD hips was less than half (p <
      0.01) the value of normal hips. Interobserver variability was approximately 10%
      of the value attributable to LCPD. This is the first known report presenting a
      technique that quantifies the three-dimensional size, deformity, growth, fit. and
      incongruity of the femoral and acetabular articulating cartilaginous surfaces of
      LCPD and contralateral normal hips. The data obtained support the use of this
      technique and provide pilot data for a future clinical study of LCPD. Objective
      assessment of cartilage shape enabled by this technique may aid future diagnoses,
      enable monitoring of three-dimensional femoral and acetabular remodeling, and
      permit quantitative assessment of treatment efficacy.

PMID- 19405085
TI  - Elevated parathyroid hormone levels after parathyroidectomy for primary
      hyperparathyroidism.
AB  - BACKGROUND: Curative parathyroidectomy is associated with elevated levels of
      parathyroid hormone (PTH) with eucalcemia. This study sought to determine the
      frequency, clinical significance, and risk factors of this finding. METHODS:
      Seventy-six consecutive patients surgically treated for primary
      hyperparathyroidism due to a single parathyroid adenoma in 2006 to 2007 were
      monitored for 1 month postoperatively; those with elevated PTH levels (>70 pg/mL)
      were monitored for 18 months. RESULTS: Nineteen patients (25%) had high
      postoperative PTH levels with normal calcium levels. Compared with the remaining
      patients, this group had a significantly higher average preoperative PTH level
      (224.89 vs 156.86 pg/mL) and a lesser intraoperative decrease in PTH.
      CONCLUSIONS: About 25% of eucalcemic patients may have elevated PTH levels after
      parathyroidectomy. A high preoperative PTH level (>225 pg/mL) may predict a
      persistently high postoperative level. Evaluation of blood and urine calcium,
      bone density, and cardiac function should be considered in affected patients.

PMID- 19405086
TI  - Management of squamous cell carcinoma of the base of tongue with chemoradiation
      and brachytherapy.
AB  - BACKGROUND: Treatment of base of tongue (BOT) squamous cell carcinoma (SCC) has
      traditionally been associated with poor prognosis and significant morbidity. We
      report a program consisting of concurrent chemoradiation followed by
      brachytherapy for these patients. METHODS: We reviewed all patients in our
      institution with previously untreated BOT SCC (1996-2004) who received this
      treatment program. RESULTS: In 88 patients (median age, 60.2 years; 37 T1/T2; 51
      T3/T4), cervical lymph node metastases were present in 71 patients (80.7%). Six
      patients had residual/subsequent cervical metastases requiring 7 neck
      dissections. Local recurrence occurred in 16 patients (18.2%) and distant
      metastases occurred in 9 patients (10.2%). Median follow-up time was 3.1 years
      (range, 0.5-7.8 years). Three-year overall survival was 80.9% (95% CI: 69.6% to
      88.3%). Locoregional control rate was 79.9% and disease-specific survival was
      69.5% at 3 years. CONCLUSIONS: Concurrent chemoradiotherapy followed with
      brachytherapy is a safe and effective method of treatment of SCC of the BOT.

PMID- 19405087
TI  - Initial clinical experience with helical tomotherapy for head and neck cancer.
AB  - BACKGROUND: To report a single-institutional experience with the use of helical
      tomotherapy (HT)-based intensity-modulated radiotherapy (IMRT) for head and neck
      cancer. METHODS: Seventy-seven consecutive patients were treated with HT for
      squamous cell carcinoma of the head and neck to a median dose of 66 Gy (range, 60
      to 72 Gy). Megavoltage CT scans were obtained as part of an image-guided
      registration protocol for patient alignment before each treatment. Concurrent
      chemotherapy was administered to 48 patients (62%). RESULTS: The 2-year estimates
      of overall survival, local-regional control, and disease-free survival were 82%,
      77%, and 71%, respectively. Spatial evaluation of local-regional failures
      revealed that 16 of the 18 patients who progressed in the primary site or neck
      failed in the high-dose planning target volume (PTV). CONCLUSIONS: HT appears to
      achieve clinical outcomes comparable to contemporary series reporting on IMRT for
      head and neck cancer.

PMID- 19405088
TI  - Image-guided surgery in an occult neck metastasis.
AB  - BACKGROUND: We report a case of a squamous cell carcinoma of the right tonsillar
      region with 5 metastatic lymph nodes and a retropharyngeal metastasis, the latter
      detected in the preoperative MRI scan. METHODS AND RESULTS: The treatment
      consisted of excision of the tumor in the oral cavity and the bilateral neck
      dissection. Despite careful exploration, a retropharyngeal metastasis was not
      identifiable during this procedure. This failure encouraged us to use navigation
      guided surgery in a second step. The difficulty in using navigation in soft
      tissue of the neck is the fixation of the neck. Therefore, a thermoplastic head
      mask, normally indicated in radiation therapy, was used for both the preoperative
      CT and navigation-guided surgery. The retropharyngeal metastasis was successfully
      excised with this method. CONCLUSION: This is the first reported attempt to use
      navigation-guided surgery in the soft tissue of the neck. It reveals new
      opportunities for navigation in the future.

PMID- 19405089
TI  - Integrated genomic and transcriptional analysis of the in vitro evolution of
      telomerase-immortalized urothelial cells (TERT-NHUC).
AB  - Much progress has been made in identifying the molecular genetic alterations that
      occur in bladder cancer. However, in many cases the genes targeted by these
      alterations are not known. Telomerase immortalized human urothelial cells (TERT
      NHUC) are a useful resource for in vitro studies of genes involved in urothelial
      transformation. When cultured under standard conditions they remain genetically
      stable but when cultured under low-density conditions they exhibit genetic
      instability and acquire chromosomal alterations. TERT-NHUC from three donors were
      cultured at low plating density and examined at four time-points during a culture
      period of 600 days. Analyses included population doubling kinetics, array-based
      CGH (aCGH), chromosome counts, fluorescence in situ hybridization (FISH),
      mutation analysis, Affymetrix gene expression analysis, Western blotting for p16,
      anchorage-independent growth and tumorigenicity assays. Alterations acquired
      during continued culture of TERT-NHUC at low density (TERT-NHUC-L) included some
      observed in urothelial carcinoma (UC) cell lines and primary UC. Examination of
      gene expression in TERT-NHUC with distinct acquired genetic aberrations may
      pinpoint genes targeted by these alterations. Data from an aCGH study of UC cell
      lines and primary tumors were examined for changes in chromosomal regions that
      also showed alterations in TERT-NHUC-L. Loss of a region on 2q including BOK was
      identified in UC cell lines and primary tumors. DNER and FRAS1 were identified as
      potential candidate genes, whose expression is altered independently of the
      acquisition of any genetic event.

PMID- 19405090
TI  - Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis.
AB  - OBJECTIVES/HYPOTHESIS: Although many proinflammatory cytokines have been
      identified in nasal polyp tissue, the initial trigger that causes this
      inflammation characterized by edema, lymphocytosis, and eosinophilia, is still
      unknown. The purpose of the present study is to identify the presence of genetic
      polymorphisms in proinflammatory, anti-inflammatory, and chemokine genes that
      might contribute to genetic susceptibility to chronic hyperplastic sinusitis with
      nasal polyposis (CHSwNP). STUDY DESIGN: Case control study. METHODS: Buccal swabs
      were taken from the left and right oral mucosal surfaces from 179 patients with
      CHSwNP and 153 nonpolyposis controls with the Purgene DNA purification protocol
      (Gentra). Genotyping assays for cytokine gene loci were performed on 14 cytokine
      genes using the iPlex Gold and the Mass Array Compact system (Sequenom, San
      Diego, CA). Tests of Hardy-Weinberg equilibrium proportions were performed
      separately in the cases and controls. Tests for evidence of association between
      alleles at each single-nucleotide polymorphism (SNP) and case-control status were
      performed using unconditional logistic regression. RESULTS: The frequency of the
      A allele in a SNP located in tumor necrosis factor (TNF)-alpha (rs1800629) is
      significantly different in patients with nasal polyposis versus controls without
      nasal polyposis, 18.6% and 11.5%, respectively with an individuals' odds of
      susceptibility to nasal polyps increasing almost two-fold (odds ratio, 1.86;
      confidence interval, 1.4-3.09) given at least one copy of the A allele at this
      SNP. All other cytokine gene polymorphisms of both inflammatory, anti
      inflammatory, and chemokine genes were not statistically different between the
      two groups. CONCLUSIONS: TNF-alpha-308, a SNP in the promoter region of this
      cytokine gene is associated with increased odds of developing nasal polyposis.
      TNF-alpha is a potent immuno-mediator and proinflammatory cytokine that has been
      implicated in the pathogenesis of a large number of human diseases. The location
      of this gene on the short arm of chromosome 6, with the major histocompatibility
      complex genes and complement, has raised the probability that polymorphism within
      this locus may contribute to a genetic association of this region of the genome
      with a wide variety of infectious and autoimmune diseases.

PMID- 19405091
TI  - Efficacy of microdebrider intracapsular adenotonsillectomy as validated by
      polysomnography.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of microdebrider intracapsular
      tonsillectomy (MT) as a treatment for pediatric obstructive sleep apnea (OSA) and
      sleep disordered breathing. STUDY DESIGN: A retrospective study evaluating
      polysomnogram outcomes for 26 patients who had undergone MT by a sole surgeon
      (M.G.) for OSA. METHODS: Chart review of patients who underwent polysomnograms
      pre- and post-adenotonsillectomy. This study represents a single pediatric
      otolaryngologist's experience at two tertiary care medical centers (Children's
      Memorial Hospital and Evanston Hospital) in the greater Chicago area. RESULTS:
      Statistically significant improvement of both the apnea-hypopnea index (AHI) and
      apnea index with P < .0001. All 26 children in the cohort had improved AHI scores
      following intracapsular tonsillectomy. Statistical analysis was performed using a
      P value < .05, which was significant. CONCLUSIONS: MT is an effective means of
      treating obstructive sleep apnea. Because of its favorable surgical outcomes and
      minimal morbidity, an increasing number of studies have found MT to be an
      excellent option for the surgical management of adenotonsillar hypertrophy in
      pediatric patients with OSA.

PMID- 19405092
TI  - Hip flexor fatigue limits walking in Charcot-Marie-Tooth disease.
AB  - Charcot-Marie-Tooth (CMT) disease results in distal lower limb weakness that
      affects walking. In this study we assess the role of the hip flexors in
      compensating for distal weakness while walking and the effects of prolonged
      walking on these putative compensatory strategies. Eighteen subjects with CMT
      disease were compared with 14 matched controls while they walked on a treadmill
      to a predetermined point of perceived effort. A significant reduction was
      observed in peak hip flexor velocity during walking and hip flexor maximal
      voluntary contraction. In a second session following selective fatigue of the hip
      flexors, hip flexor velocity decreased immediately on walking, and walking
      duration was greatly reduced. This study suggests that hip flexors compensate for
      distal weakness and that fatigue in the hip flexors can limit walking duration.
      Treatments directed toward improving proximal muscle strength may therefore help
      to delay onset of hip flexor fatigue and thus prolong walking duration.

PMID- 19405093
TI  - The identification of enzyme targets for the optimization of a valine producing
      Corynebacterium glutamicum strain using a kinetic model.
AB  - The enzyme targets for the rational optimization of a Corynebacterium glutamicum
      strain constructed for valine production are identified by analyzing the control
      of flux in the valine/leucine pathway. The control analysis is based on
      measurements of the intracellular metabolite concentrations and on a kinetic
      model of the reactions in the investigated pathway. Data-driven and model-based
      methods are used and evaluated against each other. The approach taken gives a
      quantitative evaluation of the flux control and it is demonstrated how the
      understanding of flux control is used to reach specific recommendations for
      strain optimization. The flux control coefficients (FCCs) with respect to the
      valine excretion rate were calculated, and it was found that the control is
      distributed mainly between the acetohydroxyacid synthase enzyme (FCC = 0.32), the
      branched chain amino acid transaminase (FCC = 0.27), and the exporting
      translocase (FCC = 0.43). The availability of the precursor pyruvate has
      substantial influence on the valine flux, whereas the cometabolites are less
      important as demonstrated by the calculation of the respective response
      coefficients. The model is further used to make in-silico predictions of the
      change in valine flux following a change in enzyme level. A doubling of the
      enzyme level of valine translocase will result in an increase in valine flux of
      31%. By optimizing the enzyme levels with respect to valine flux it was found
      that the valine flux can be increased by a factor 2.5 when the optimal enzyme
      levels are implemented.

PMID- 19405095
TI  - IBDfinder and SNPsetter: tools for pedigree-independent identification of
      autozygous regions in individuals with recessive inherited disease.
AB  - Autozygosity mapping of recessive genes can be performed on a small number of
      affected individuals from consanguineous pedigrees. With the advent of microarray
      SNP analysis, acquiring genotype data has become extremely simple and quick, in
      comparison to gene mapping with microsatellite markers. However, the subsequent
      data analysis required to identify autozygous regions can still be a significant
      obstacle. For rapid gene identification, it may be desirable to integrate
      information from heterogeneous groups of affected individuals, both familial and
      isolated, under various assumptions of ancestry and locus heterogeneity, that are
      not amenable to formal linkage analysis. Unfortunately, there are few computer
      programs aimed specifically at facilitating this type of data sifting. Here, we
      demonstrate two new programs that facilitate the identification of autozygous
      regions within a heterogeneous SNP dataset derived from familial and sporadic
      affected individuals.

PMID- 19405094
TI  - Relative contribution of simple mutations vs. copy number variations in five
      Parkinson disease genes in the Belgian population.
AB  - The relative contribution of simple mutations and copy number variations (CNVs)
      in SNCA, PARK2, PINK1, PARK7, and LRRK2 to the genetic etiology of Parkinson
      disease (PD) is still unclear because most studies did not completely analyze
      each gene. In a large group of Belgian PD patients (N = 310) and control
      individuals (N = 270), we determined the mutation frequency of both simple
      mutations and CNVs in these five PD genes, using direct sequencing, multiplex
      amplicon quantification (MAQ), and real-time PCR assays. Overall, we identified
      14 novel heterozygous variants, of which 11 were absent in control individuals.
      We observed eight PARK2 (multiple) exon multiplications in PD patients and one
      exon deletion in a control individual. Furthermore, we identified one SNCA whole
      gene duplication. The PARK2 and LRRK2 mutation frequencies in Belgian PD patients
      were similar to those reported in other studies. However, at this stage the true
      pathogenic nature of some heterozygous mutations in recessive genes remains
      elusive. Furthermore, though mutations is SNCA, PINK1, and PARK7 are rare, our
      identification of a SNCA duplication confirmed that screening of these genes
      remains meaningful.

PMID- 19405096
TI  - Identification and characterization of SMPD1 mutations causing Niemann-Pick types
      A and B in Spanish patients.
AB  - Niemann-Pick disease (NPD) types A/B are both caused by a deficiency of lysosomal
      acid sphingomyelinase and display autosomal recessive inheritance. These two
      types of the disease were described according to the presence (type A) or absence
      (type B) of neurological symptoms. We present a molecular analysis of 19 Spanish
      NPD A/B patients and two from Maghreb. Eight of the patients had type A and 13
      had type B NPD. All mutant SMPD1 alleles were identified, including 17 different
      mutations, 10 of which were novel. The only frequent mutations in the 21 NPD
      patients were c.1823_1825delGCC (p.R608del) (38%) and c.1445C>A (p.A482E) (9%).
      Genotype-phenotype correlations were established for most of the mutations and,
      in particular, the p.R608del-type B association was confirmed. This mutation
      accounts for 61.5% of the mutant alleles in the type B subgroup of patients.
      Expression studies performed on six of the identified mutations confirmed them to
      be disease-causing due to their low enzyme activity. An allele with a mutation
      affecting a noncanonical donor splice site produced only aberrant mRNAs,
      corresponding to previously reported nonfunctional SMPD1 minor transcripts. This
      study is the first exhaustive mutational analysis of Spanish Niemann-Pick A/B
      disease patients.

PMID- 19405098
TI  - ZOONET: perspectives on the evolution of animal form. Meeting report.
AB  - What drives evolution? This was one of the main questions raised at the final
      ZOONET meeting in Budapest, Hungary, in November 2008. The meeting marked the
      conclusion of ZOONET, an EU-funded Marie-Curie Research Training Network
      comprising nine research groups from all over Europe (Max Telford, University
      College London; Michael Akam, University of Cambridge; Detlev Arendt, EMBL
      Heidelberg; Maria Ina Arnone, Stazione Zoologica Anton Dohrn Napoli; Michalis
      Averof, IMBB Heraklion; Graham Budd, Uppsala University; Richard Copley,
      University of Oxford; Wim Damen, University of Cologne; Ernst Wimmer, University
      of Gottingen). ZOONET meetings and practical courses held during the past four
      years provided researchers from diverse backgrounds--bioinformatics,
      phylogenetics, embryology, palaeontology, and developmental and molecular biology
      -the opportunity to discuss their work under a common umbrella of evolutionary
      developmental biology (Evo Devo). The Budapest meeting emphasized in-depth
      discussions of the key concepts defining Evo Devo, and bringing together ZOONET
      researchers with external speakers who were invited to present their views on the
      evolution of animal form. The discussion sessions addressed four main topics: the
      driving forces of evolution, segmentation, fossils and phylogeny, and the future
      of Evo Devo.

PMID- 19405097
TI  - Identification and characterization of mutations in FANCL gene: a second case of
      Fanconi anemia belonging to FA-L complementation group.
AB  - Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder
      characterized by aplastic anemia, cancer susceptibility and cellular sensitivity
      to DNA crosslinking agents. Eight FA proteins (FANCA, FANCB, FANCC, FANCE, FANCF,
      FANCG, FANCL and FANCM) and three non-FA proteins (FAAP100, FAAP24 and HES1) form
      an FA nuclear core complex, which is required for monoubiquitination of the
      FANCD2-FANCI dimer upon DNA damage. FANCL possesses a PHD/RING-finger domain and
      is a putative E3 ubiquitin ligase subunit of the core complex. In this study, we
      report an FA patient with an unusual presentation belonging to the FA-L
      complementation group. The patient lacks an obvious FA phenotype except for the
      presence of a cafe-au-lait spot, mild hypocellularity and a family history of
      leukemia. The molecular diagnosis and identification of the FA subgroup was
      achieved by FA complementation assay. We identified bi-allelic novel mutations in
      the FANCL gene and functionally characterized them. To the best of our knowledge,
      this is the second reported case belonging to the FA-L complementation group.

PMID- 19405099
TI  - Susceptibility of mouse minute virus to inactivation by heat in two cell culture
      media types.
AB  - Viral contaminations of biopharmaceutical manufacturing cell culture facilities
      are a significant threat and one for which having a risk mitigation strategy is
      highly desirable. High temperature, short time (HTST) mammalian cell media
      treatment may potentially safeguard manufacturing facilities from such
      contaminations. HTST is thought to inactivate virions by denaturing proteins of
      the viral capsid, and there is evidence that HTST provides ample virucidal
      efficacy against nonenveloped or naked viruses such as mouse minute virus (MMV),
      a parvovirus. The aim of the studies presented herein was to further delineate
      the susceptibility of MMV, known to have contaminated mammalian cell
      manufacturing facilities, to heat by exposing virus-spiked cell culture media to
      a broad range of temperatures and for various times of exposure. The results of
      these studies show that HTST is capable of inactivating MMV by three orders of
      magnitude or more. Thus, we believe that HTST is a useful technology for the
      purposes of providing a barrier to adventitious contamination of mammalian cell
      culture processes in the biopharmaceutical industry.

PMID- 19405100
TI  - Intraneuronal signaling pathways of metallothionein.
AB  - Metallothionein (MT) belongs to a family of metal-binding cysteine-rich proteins
      comprising several structurally related proteins implicated in tissue protection
      and regeneration after injuries and functioning as antiapoptotic antioxidants in
      neurological disorders. This has been demonstrated in animals receiving MT
      treatment and in mice with endogenous MT overexpression or null mutation during
      various experimental models of neuropathology, and also in patients with
      Alzheimer's disease and amyotrophic lateral sclerosis. Exogenously applied MT
      increases neurite outgrowth and neuronal survival in rat cerebellar, hippocampal,
      dopaminergic, and cortical neurons in vitro. In this study, the intraneuronal
      signaling involved in MT-mediated neuritogenesis was examined. The MT-induced
      neurite outgrowth in cultures of cerebellar granule neurons was dependent on
      activation of a heterotrimeric G-protein-coupled pathway but not on protein
      tyrosine kinases or on receptor tyrosine kinases. Activation of phospholipase C
      was necessary for MT-induced neurite outgrowth, and furthermore it was shown that
      inhibition of several intracellular protein kinases, such as protein kinase A,
      protein kinase C, phosphatidylinositol 3-kinase, Ca(2+)/calmodulin kinase-II, and
      mitogen-activated protein kinase kinase, abrogated the MT-mediated neuritogenic
      response. In addition, exogenously applied MT resulted in a decrease in
      phosphorylation of intraneuronal kinases implicated in proinflammatory reactions
      and apoptotic cell death, such as glycogen synthase-serine kinase 3alpha, Jun,
      and signal transducer and activator of transcription 3. This paper elucidates the
      intraneuronal molecular signaling involved in neuroprotective effects of MT.

PMID- 19405101
TI  - Acetylcholine synthesis and release in NIH3T3 cells coexpressing the high
      affinity choline transporter and choline acetyltransferase.
AB  - Acetylcholine (ACh) is known to be a key neurotransmitter in the central and
      peripheral nervous systems, but it is also produced in a variety of non-neuronal
      tissues and cells, including lymphocytes, placenta, amniotic membrane, vascular
      endothelial cells, keratinocytes, and epithelial cells in the digestive and
      respiratory tracts. To investigate contribution made by the high-affinity choline
      transporter (CHT1) to ACh synthesis in both cholinergic neurons and nonneuronal
      cells, we transfected rat CHT1 cDNA into NIH3T3ChAT cells, a mouse fibroblast
      line expressing mouse choline acetyltransferase (ChAT), to establish the
      NIH3T3ChAT 112-1 cell line, which stably expresses both CHT1 and ChAT. NIH3T3ChAT
      112-1 cells showed increased binding of the CHT1 inhibitor [(3)H]hemicholinium-3
      (HC-3) and greater [(3)H]choline uptake and ACh synthesis than NIH3T3ChAT 103-1
      cells, a CHT1-negative control cell line. HC-3 significantly inhibited ACh
      synthesis in NIH3T3ChAT 112-1 cells but did not affect synthesis in NIH3T3ChAT
      103-1 cells. ACh synthesis in NIH3T3ChAT 112-1 cells was also reduced by
      amiloride, an inhibitor of organic cation transporters (OCTs) involved in low
      affinity choline uptake, and by procaine and lidocaine, two local anesthetics
      that inhibit plasma membrane phospholipid metabolism. These results suggest that
      CHT1 plays a key role in ACh synthesis in NIH3T3ChAT 112-1 cells and that choline
      taken up by OCTs or derived from the plasma membrane is also utilized for ACh
      synthesis in both cholinergic neurons and nonneuronal cholinergic cells, such as
      lymphocytes.

PMID- 19405103
TI  - Specificity of the second messenger pathways involved in basic fibroblast growth
      factor-induced survival and neurite growth in chick ciliary ganglion neurons.
AB  - Basic fibroblast growth factor (bFGF) exerts multiple neurotrophic actions on
      cultured neurons from the ciliary ganglion of chick embryo, among them promotion
      of neuronal survival and of neurite outgrowth. To understand the specificity of
      the signal transduction cascades involved in the control of these processes, we
      used pharmacological inhibitors of the three main effectors known to act
      downstream of the bFGF receptor (FGFR): phospholipase Cgamma (PLCgamma), mitogen
      activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3-K).
      Neuronal survival was assessed at 24 and 48 hr; neurite growth was analyzed both
      on dissociated neurons and on explants of whole ganglia. Our data show that only
      the PI3-K pathway is involved in the survival-promoting effect of bFGF; on the
      other hand, all three effectors converge on the enhancement of neurite outgrowth,
      both on isolated neurons and in whole ganglia.

PMID- 19405102
TI  - The two-hydrophobic domain tertiary structure of reticulon proteins is critical
      for modulation of beta-secretase BACE1.
AB  - beta-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is a membrane
      bound protease that is essential for the production of beta-amyloid protein
      (Abeta). Given the crucial role of Abeta accumulation in Alzheimer's disease
      (AD), inhibition of BACE1 activity may represent a feasible therapeutic strategy
      in the treatment of AD. Recently, we and others identified reticulon 3 (RTN3) and
      reticulon 4-B/C (RTN4-B/C or Nogo-B/C) as membrane proteins that interact with
      BACE1 and inhibit its ability to produce Abeta. In this study, we employed
      various mutants of RTN3 and RTN4-C and C. elegans RTN to investigate the
      molecular mechanisms by which RTNs regulate BACE1. We found that RTN3 mutants
      lacking the N-terminal or C-terminal or loop domain as well as a RTN4-C mutant
      lacking the C-terminal domain bound to BACE1 comparably to wild-type RTN3 and
      RTN4-C. Furthermore, overexpression of wild-type RTN3, RTN4-C, and these RTN
      mutants similarly reduced Abeta40 and Abeta42 secretion by cells expressing
      Swedish mutant APP. C. elegans RTN, which has low homology to human RTNs, also
      interacted with BACE1 and inhibited Abeta secretion. In contrast, two RTN3
      mutants containing deletions of the first or second potential transmembrane
      domains and an RTN3 swap mutant of the second transmembrane domain bound BACE1
      but failed to inhibit Abeta secretion. Collectively, these results suggest that
      the two-transmembrane-domain tertiary structure of RTN proteins is critical for
      the ability of RTNs to modulate BACE1 activity, whereas N-terminal, C-terminal
      and loop regions are not essential for this function.

PMID- 19405104
TI  - Stereological investigation of age-related changes of myelinated fibers in the
      rat cortex.
AB  - In the present study, the cortex volume, total volume, total length and mean
      diameter of the myelinated fibers in the cortices of young, middle-aged, and aged
      Long-Evans rats were quantitatively investigated by using stereological methods
      and electron microscopy techniques. There were no significant differences in the
      myelinated fibers between young and middle-aged rat cortex. The cortex volume and
      the total length of the myelinated fibers in the cortex of aged rats were
      significantly lower than those of young and middle-aged rats. However, no
      significant difference was found in the total volume of the myelinated fibers
      among three groups. The disproportional changes in the total length and total
      volume of the myelinated fibers in the cortex of aged rats and the absolute
      distribution of the total length of the myelinated fibers in the cortex of the
      three groups suggested that the age-induced decrease of the myelinated fibers
      might be due mainly to a loss of the myelinated fibers with smaller diameters.
      The present results together with our previous findings indicated that the age
      related changes of the myelinated fibers occurred widely in the central nervous
      system and that the age-related changes of the myelinated fibers in cortex
      occurred later than those in white matter.

PMID- 19405106
TI  - Specific PCR product primer design using memetic algorithm.
AB  - To provide feasible primer sets for performing a polymerase chain reaction (PCR)
      experiment, many primer design methods have been proposed. However, the majority
      of these methods require a relatively long time to obtain an optimal solution
      since large quantities of template DNA need to be analyzed. Furthermore, the
      designed primer sets usually do not provide a specific PCR product size. In
      recent years, evolutionary computation has been applied to PCR primer design and
      yielded promising results. In this article, a memetic algorithm (MA) is proposed
      to solve primer design problems associated with providing a specific product size
      for PCR experiments. The MA is compared with a genetic algorithm (GA) using an
      accuracy formula to estimate the quality of the primer design and test the
      running time. Overall, 50 accession nucleotide sequences were sampled for the
      comparison of the accuracy of the GA and MA for primer design. Five hundred runs
      of the GA and MA primer design were performed with PCR product lengths of 150-300
      bps and 500-800 bps, and two different methods of calculating T(m) for each
      accession nucleotide sequence were tested. A comparison of the accuracy results
      for the GA and MA primer design showed that the MA primer design yielded better
      results than the GA primer design. The results further indicate that the proposed
      method finds optimal or near-optimal primer sets and effective PCR products in a
      dry dock experiment. Related materials are available online at
      http://bio.kuas.edu.tw/ma-pd/.

PMID- 19405105
TI  - Identification of major S-nitrosylated proteins in murine experimental autoimmune
      encephalomyelitis.
AB  - Nitrosative stress has been implicated in the pathophysiology of several CNS
      disorders, including multiple sclerosis (MS) and its animal model experimental
      autoimmune encephalomyelitis (EAE). We have recently shown that protein
      nitrosothiols (PrSNOs) accumulate in the brain of MS patients, and there is
      indirect evidence that PrSNO levels are also increased in EAE. In this study we
      sought to identify the major PrSNOs in the spinal cord of EAE animals prepared by
      active immunization of C57/BL6 mice with MOG(35-55) peptide. For this purpose,
      PrSNOs from control and EAE mice at various disease stages were derivatized with
      HPDP-biotin, and the biotinylated proteins were isolated with streptavidin
      agarose. Proteins from total and streptavidin-bound fractions were then analyzed
      by Western blotting using antibodies against the major S-nitrosylated substrates
      of CNS tissue. With this approach we found that the proportion of S-nitrosylated
      neurofilament proteins, NMDA receptors, alpha/beta-tubulin, beta-actin, and GAPDH
      is increased in EAE. Other potential substrates either were not S-nitrosylated in
      vivo (HCN3, HSP-72, CRMP-2, gamma-actin, calbindin) or their S-nitrosylation
      levels were unaltered in EAE (Na/K ATPase, hexokinase, glycogen phosphorylase).
      We also discovered that neuronal specific enolase is the major S-nitrosylated
      protein in acute EAE. Given that S-nitrosylation affects protein function, it is
      likely that the observed changes are significant to the pathophysiology of
      inflammatory demyelination.

PMID- 19405108
TI  - House dust mite protozoon on a nasal smear in a case of allergic rhinitis.

PMID- 19405109
TI  - Utility of glypican-3 and survivin in differentiating hepatocellular carcinoma
      from benign and preneoplastic hepatic lesions and metastatic carcinomas in liver
      fine-needle aspiration biopsies.
AB  - Glypican-3 (GPC-3), a membrane-anchored heparin sulfate proteoglycan, has been
      shown to be expressed in approximately 80% of hepatocellular carcinoma (HCC) but
      not in benign hepatic lesions. Survivin, a novel inhibitor of apoptosis, and a
      prognostic marker, has also been expressed in HCC. We evaluated these two
      immunomarkers (GPC-3 and survivin) in differentiating HCC from benign and
      preneoplastic hepatic lesions and metastatic carcinomas, comparing them to HepPar
      1 (hepatocyte paraffin-1) in liver fine-needle aspiration biopsies
      (FNAB).Immunohistochemistry for GPC-3, survivin and HepPar-1 was performed on 92
      FNAB including HCC, hepatic cirrhosis, focal nodular hyperplasia (FNH), hepatic
      adenoma, dysplastic hepatic nodules and metastatic carcinomas. Immunostaining was
      scored as positive, if > or =10% of tumor cells stained.GPC-3 is immunoexpressed
      in 56.8% of HCC, but not in benign and preneoplastic hepatic lesions, or
      metastatic carcinomas; whereas survivin is expressed in HCC (86.4%), benign
      hepatic lesions (85.7%), dysplastic hepatic nodules (100%) and metastatic
      carcinomas (94.3%). HepPar-1 is immunoexpressed in HCC (72.7%), benign hepatic
      lesions (100%), dysplastic nodules (100%) and metastatic carcinomas (2.9%). The
      sensitivity and specificity of GPC-3, survivin and HepPar-1 for detection of HCC
      are 56.8 and 100%, 86.4 and 6.3%, 72.7 and 70.8%, respectively.GPC-3 is a
      reliable and more specific immunohistochemical marker than survivin for the
      diagnosis of HCC in FNAB. HepPar-1, although a more sensitive marker than GPC-3,
      has a lower specificity for detection of HCC. Our data supports the potentially
      significant diagnostic utility of GPC-3 in FNABs in differentiating primary
      malignant from benign and preneoplastic liver lesions, and metastatic carcinomas.

PMID- 19405107
TI  - A novel inducible tyrosine kinase receptor to regulate signal transduction and
      neurite outgrowth.
AB  - Nervous system growth factor gene delivery can promote axonal growth and prevent
      cell death in animal models of CNS trauma and neurodegenerative diseases. The
      ability to regulate growth factor expression or signaling pathways downstream
      from growth factor receptors remains a desirable goal for in vivo gene transfer.
      To achieve precise pharmacological modulation of neurotrophin activity, we have
      generated a chimeric trkA receptor (ItrkA) by fusing the entire intracellular
      domain of the trkA high-affinity NGF receptor to two intracellular, modified
      FK506 binding domains for the synthetic small molecule dimerization ligand
      AP20187. Rat PC12 cells were transduced with lentiviral vectors containing ItrkA
      and green fluorescent protein (GFP; via an internal ribosome entry site).
      Treatment of ItrkA-expressing PC12 cells with AP20187 induced neurite outgrowth
      and differentiation in a time- and dose-dependent fashion, with a half-maximal
      response at a concentration of 1 nM AP20187. Seventy percent of cells responded
      to AP20187 by day 3. Western blots demonstrated that AP20187 treatment resulted
      in phosphorylation of Erk1/2 and Akt in ItrkA-transduced PC12 cells but not in
      nontransduced, naive cells. Phosphorylation levels were comparable to levels
      obtained with 50 ng/ml nerve growth factor (NGF). In addition, ItrkA lentiviral
      transduction of primary E15 dorsal root ganglion neurons significantly increased
      neurite growth three- to fourfold in the presence of AP20187 compared with
      control GFP transduced and naive neurons. These results demonstrate that small
      ligand-induced dimerization of the intracellular domain of trkA can efficiently
      simulate the biological activity of NGF and provide a means to regulate
      intracellular neurotrophin receptor signaling.

PMID- 19405110
TI  - Cervical tuberculosis detection in Papanicolaou-stained smear: case report with
      review of literature.
AB  - Genital tract tuberculosis is usually secondary to an extragenital tubercular
      focus. Cervical tuberculosis, however, is rare accounting for up to 3% of all
      genital tract diseases. The diagnosis of tuberculosis is usually established on
      multiple cervical biopsies followed by bacteriological confirmation. There are
      only a handful of reports on the diagnosis of tubercular cervicitis in cervical
      smears. We hereby report a case of cervical tuberculosis which was diagnosed on
      cervical smear. We also carried out a brief literature review of the cases
      diagnosed previously on cervical smear.

PMID- 19405111
TI  - Fine-needle aspiration cytology of metastatic eccrine porocarcinoma.
AB  - Eccrine porocarcinoma (EP), although rare, is widely recognized as the most
      common malignant sweat gland tumor. EP typically grows slowly and usually is
      cured by surgical excision with clear margins. An elevated mortality rate,
      however, is observed when regional lymph nodes are involved. We herein describe
      cytohistologic findings in a case of metastatic EP. An 86-year-old man with a
      history of EP of the left lateral ankle and squamous cell carcinoma in situ
      (Bowen's disease) of the penis presented with enlarged left inguinal lymph nodes.
      A superficial fine-needle aspiration (FNA) was performed and demonstrated a
      hypercellular sample with discohesive clusters and/or individual tumor cells. The
      tumor cells were round or oval with most of the cells showing dense, refractile
      cytoplasm. Intracytoplasmic vacuoles were readily appreciated in some of the
      cells. Nuclear enlargement, high N/C ratio, nuclear hyperchromasia, bi- and
      multinucleation, and prominent nucleoli were seen. A diagnosis of metastatic
      eccrine porocarcinoma was rendered. Enlarged retroperitoneal lymph nodes were
      detected and CT-guided left retroperitoneal core biopsy was performed 1 week
      later. The biopsy revealed features consistent with metastatic eccrine
      porocarcinoma.

PMID- 19405112
TI  - Fine-needle aspiration cytology in the diagnosis of malignant proliferating
      trichilemmal tumor: Report of a case and review of the literature.
AB  - Malignant proliferating trichilemmal tumor is a rare cutaneous neoplasm derived
      from the outer root sheath of the hair follicle. Fine-needle aspiration cytology
      is being increasingly used in the investigation of primary and metastatic
      cutaneous tumors. However, there are few reports on the cytology of trichilemmal
      tumors in the literature. We describe the cytological features of this uncommon
      adnexal tumor presenting as a scalp mass in a 58-year-old woman. In view of its
      aggressive biological behavior, it is crucial for cytologists to be aware of this
      rare lesion and distinguish it from primary cutaneous squamous-cell carcinoma.
      The differences on fine-needle aspiration cytology can be subtle and pose
      problems in diagnosis.

PMID- 19405113
TI  - Mycobacterium avium complex infection in a neck abscess: a diagnostic pitfall in
      fine-needle aspiration biopsy of head and neck lesions.
AB  - Fine-needle aspiration biopsy (FNAB) is a useful tool in the diagnosis of
      mycobacterial disease, especially Mycobacterium tuberculosis. However,
      nontuberculous mycobacterial infection diagnosed with FNAB material is much
      rarer, with Mycobacterium avium complex being the most common. In this report, we
      present the case of a 21-year-old HIV positive man, who presented with a
      unilateral, tender, enlarging cervical neck mass. FNAB had revealed acute
      inflammation. Mycobacterium avium complex grew in culture from the material that
      was aspirated and was confirmed by DNA probe. Because of the paucity of articles
      on this subject in the cytology literature, it is important to reiterate the
      value of the material aspirated at the bedside and the clinic in the diagnosis of
      infectious disease. When faced with antibiotic-resistant cellulitis and
      abscesses, the FNAB material must be sent for acid fast bacteria smears and
      culture.

PMID- 19405114
TI  - Genomic instability of micronucleated cells revealed by single-cell comparative
      genomic hybridization.
AB  - Nuclear variation in size and shape and genomic instability are hallmarks of
      dedifferentiated cancer cells. Although micronuclei are a typical long-term
      consequence of DNA damage, their contribution to chromosomal instability and
      clonal diversity in cancer disease is unclear. We isolated cancer cells with or
      without micronuclei to perform genomic analysis. Cell suspensions of HT1080
      fibrosarcoma cells from either 2D culture or after isolation from 3D collagen
      matrix culture were stained with Hoechst 33342 and after classification for
      presence or absence of a micronucleus via bright-field and epifluorescence
      microscopy, cells were individually aspirated with a micropipette. Subsequently,
      whole-genome amplification and single-cell comparative genomic hybridization
      (CGH) were applied to detect genomic aberrations. The data show a high-fidelity
      isolation and genome amplification that lacks adverse effects by prior Hoechst
      33342 staining. HT1080 cells showed a high degree of divergent amplifications,
      but neither location nor frequency of aberrations was dependent on 2D or 3D
      culture conditions or micronucleation. Thus, single-cell selection of defined
      nuclear states is amenable to single-cell CGH and here provides first insight
      into the aberration drift and genomic diversity in cancer cells with and without
      micronuclei.

PMID- 19405115
TI  - Fluorescence activated cell sorting of live female germ cells and somatic cells
      of the mouse fetal gonad based on forward and side scattering.
AB  - Analysis of female mammalian germ cells has been hindered by difficulties in
      isolating high purity germ cell populations from embryonic and fetal gonads.
      Meiotic prophase stage oocytes are particularly difficult to isolate due to the
      lack of suitable surface markers. Oct4 promoter driven GFP expression has been
      used to distinguish germ cells/oocytes (GFP positive) from somatic cells (GFP
      negative), however, the requirement for transgenic animals has limited the use of
      this technique. We analyzed the side- and forward scattering properties of living
      cell populations obtained from fetal ovaries of Oct4-GFP transgenic and wild-type
      mice. On the basis of these measurements, we defined criteria that allow the
      discrimination and identification of germ cells and somatic cells within cell
      suspensions of nontransgenic female fetal gonads. The described method is
      suitable for the isolation of populations of germ cells and somatic cells of
      higher than 90% purity. We also demonstrated that the sorted cells can be used in
      downstream immunofluorescence and RT-PCR applications. Hence, we conclude that
      side and forward scattering based sorting of female germ cells is a valuable tool
      that will benefit the understanding of female gametogenesis.

PMID- 19405116
TI  - The beta-thymosins: intracellular and extracellular activities of a versatile
      actin binding protein family.
AB  - The beta-thymosins are N-terminally acetylated peptides of about 5 kDa molecular
      mass and composed of about 40-44 amino acid residues. The first member of the
      family, thymosin beta4, was initially isolated from thymosin fraction 5, prepared
      in five steps from calf thymus. Thymosin beta4 was supposed to be specifically
      produced and released by the thymic gland and to possess hormonal activities
      modulating the immune response. Various paracrine effects have indeed been
      reported for these peptides such as cardiac protection, angiogenesis, stimulation
      of wound healing, and hair growth. Besides these paracrine effects, it was noted
      that beta-thymosins occur in high concentration in the cytoplasm of many
      eukaryotic cells and bind to the cytoskeletal component actin. Subsequently it
      became apparent from in vitro experiments that they preferentially bind to
      monomeric (G-)actin and stabilize it in its monomeric form. Due to this ability
      the beta-thymosins are the main intracellular actin sequestering factor, i.e.,
      they posses the ability to remove monomeric actin from the dynamic assembly and
      disassembly processes of the actin cytoskeleton that constantly occur in
      activated cells. In this review we will concentrate on the intracellular activity
      and localization of the beta-thymosins, i.e., their modulating effect on the
      actin cytoskeleton.

PMID- 19405117
TI  - Chemical networks with inflows and outflows: a positive linear differential
      inclusions approach.
AB  - Certain mass-action kinetics models of biochemical reaction networks, although
      described by nonlinear differential equations, may be partially viewed as state
      dependent linear time-varying systems, which in turn may be modeled by convex
      compact valued positive linear differential inclusions. A result is provided on
      asymptotic stability of such inclusions, and applied to a ubiquitous biochemical
      reaction network with inflows and outflows, known as the futile cycle. We also
      provide a characterization of exponential stability of general homogeneous
      switched systems which is not only of interest in itself, but also plays a role
      in the analysis of the futile cycle.

PMID- 19405118
TI  - Targeting AKT with the proapoptotic peptide, TAT-CTMP: a novel strategy for the
      treatment of human pancreatic adenocarcinoma.
AB  - Pancreatic adenocarcinoma carries an ominous prognosis and has little effective
      treatment. Several studies have demonstrated that the potently antiapoptotic
      phosphatidyl inositol 3'-kinase (PI3K)-protein kinase B/AKT pathway is active in
      pancreas cancer. A recent study identified an endogenous AKT antagonist, carboxyl
      terminal modulator protein (CTMP). CTMP inhibits the phosphorylation of AKT,
      preventing full activation of the kinase. We screened several cell permeable
      peptides from the N-terminal domain of CTMP (termed TAT-CTMP1-4) in vitro and
      found one that caused significant apoptosis in pancreatic adenocarcinoma cell
      lines. An inactive variant of this peptide was synthesized and used as a negative
      control. In all cell lines tested, TAT-CTMP4 induced a dose-dependent increase in
      apoptosis as detected by %-TUNEL positive cells and %-active caspase-3 (% active
      caspase-3 ranged from 31.2 to 61.9 at the highest dose tested (10 microM). A
      screening of various cell and tissue types revealed that the proapoptotic
      activity was highest in pancreatic adenocarcinoma. TAT-CTMP induced similar
      levels of active caspase-3 as several other known inducers of apoptosis:
      gemcitabine, radiation therapy, wortmannin and recombinant tumor necrosis factor
      (TNF)-alpha. No apoptosis was observed in donor human peripheral blood
      mononuclear cells (PBMC, p < 0.01). We further showed that TAT-CTMP4 could
      augment either gemcitabine chemotherapy or radiation therapy, standard therapies
      for pancreas cancer. Pancreatic adenocarcinoma xenografts treated with a single
      dose of TAT-CTMP4 demonstrated a marked increase in caspase-3 positive tumor
      cells when compared with untreated controls. Additionally, pancreatic
      adenocarcinoma allografts treated with intratumoral TAT-CTMP and systemic
      gemcitabine displayed a significantly smaller tumor burden while undergoing
      treatment than mice in control groups (p < 0.001). These data indicate that
      inhibiting AKT with CTMP may be of therapeutic benefit in the treatment of
      pancreatic adenocarcinoma and, when combined with established therapies, may
      result in an increase in tumor cell death.

PMID- 19405119
TI  - Identification of integrins alpha6 and beta7 as c-Jun- and transformation
      relevant genes in highly invasive fibrosarcoma cells.
AB  - Understanding the mechanisms of tumor cell invasion is essential for our attempts
      to prevent cancer deaths. We screened by DNAmicroarrays the c-Jun- and
      transformation-related gene expression changes in S-adenosylmethionine
      decarboxylase (AdoMetDC)-overexpressing mouse fibroblasts that are highly
      invasive in vivo, and their derivatives expressing a tetracycline-inducible
      dominant-negative mutant of c-Jun (TAM67) or c-Jun shRNA. Among the small set of
      target genes detected were integrins alpha6 and beta7, cathepsin L and thymosin
      beta4, all upregulated in the AdoMetDC-transformed cells and downregulated upon
      reversal of transformation by TAM67 or c-Jun shRNA. The upregulation of integrin
      alpha6 subunit, pairing with integrin beta1, endowed the transformed cells with
      the capability to attach to basement membrane laminin and to spread. Further,
      inhibition of integrin alpha6 or beta1 function with neutralizing antibodies
      blocked the invasiveness of AdoMetDC-transformants and human HT-1080 fibrosarcoma
      cells in three-dimensional Matrigel. Moreover, immunohistochemical analyses
      showed strong integrin alpha6 staining in high-grade human fibrosarcomas. Our
      data show that c-Jun can regulate all three key steps of invasion: cell adhesion
      (integrin alpha6), basement membrane/extracellular matrix degradation (cathepsin
      L) and cell migration (thymosin beta4). In addition, this is the first study to
      associate integrin beta7, known as a leukocyte-specific integrin binding to
      endothelial/epithelial cell adhesion molecules, with the transformed phenotype in
      cells of nonleukocyte origin. As tumor cell invasion is a prerequisite for
      metastasis, the observed critical role of integrin alpha6beta1 in fibrosarcoma
      cell invasion/spreading allures testing antagonists to integrin alpha6beta1,
      alone or combined with inhibitors of cathepsin L and thymosin beta4, as
      chemotherapeutic agents.

PMID- 19405120
TI  - Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells
      mediated by exosomal nanoparticles.
AB  - We previously reported that exosomal nanoparticles secreted by human pancreatic
      tumoral cell lines decrease tumoral cell proliferation through the mitochondria
      dependent apoptotic pathway, because of activation of pro-apoptotic phosphatase
      and tensin homolog deleted on chromosome 10 (PTEN) and of glucose synthase kinase
      3beta (GSK-3beta). Interactions between exosomal nanoparticles and cells are
      thought to involve membrane lipid rafts. However, the underlying mechanism is
      unknown. Here, we report that the interaction of exosomal nanoparticles with
      pancreatic cancer cells led to decreased expression of hairy and enhancer-of
      split homolog-1 (Hes-1), the intranuclear target of Notch-1 signaling pathway,
      and to activation of the apoptotic pathway after a cell cycle arrest in G(0)G(1)
      phase. Strikingly, the expression level of Notch-1 pathway components was
      critical, because exosomal nanoparticles decreased the proliferation of cells in
      which these partners are either weakly represented, in differentiated
      adenocarcinoma cells, or inhibited, in poorly differentiated carcinoma cells, by
      blocking presenilin in the gamma-secretase complex that regulates the Notch-1
      pathway. Overexpression of Notch-1 intracellular domain resulted in the reversion
      of the cell proliferation inhibition promoted by exosomal nanoparticles. Blocking
      presenilin unexpectedly resulted in activation of PTEN and GSK-3beta. Conversely,
      inhibiting either PTEN or GSK-3beta increased Hes-1 expression and partially
      counteracted the inhibition of proliferation promoted by exosomal nanoparticles,
      highlighting reciprocal regulations between Notch signaling and PTEN/GSK-3beta.
      We concluded that interactions of exosomal nanoparticles with target cells, at
      lipid rafts where Notch-1 pathway partners are localized, hampered the
      functioning of the Notch-1 survival pathway and activated the apoptotic pathway,
      which determines tumoral cell fate.

PMID- 19405122
TI  - Establishing a relationship between activity reduction in human perirhinal cortex
      and priming.
AB  - Perirhinal neurons exhibit reduced firing rates with stimulus repetition, a
      phenomenon termed "repetition suppression." However, relationships between
      perirhinal repetition suppression and behavioral expressions of memory remain
      unclear. We used anatomically constrained functional magnetic resonance imaging
      (fMRI) to assess relationships between perirhinal activity and priming, a type of
      implicit memory. Priming was expressed as speeded animacy judgments for old
      versus new words. Concurrently, old words elicited less neural activity in
      bilateral perirhinal cortex. The magnitude of the left perirhinal activity
      reduction selectively predicted the magnitude of behavioral priming in an across
      subjects hierarchical linear regression analysis. These findings have
      implications for considering how perirhinal cortex may contribute to different
      neurocognitive functions, possibly including both implicit memory and familiarity
      based recognition. This study documents the first evidence linking behavioral
      measures of priming to information processing in perirhinal cortex.

PMID- 19405121
TI  - BCL6 cooperates with CD40 stimulation and loss of p53 function to rapidly
      transform primary B cells.
AB  - The BCL6 transcriptional repressor protein has been shown to promote B-cell
      lymphoma in transgenic mouse models. The mechanism by which BCL6 transforms
      primary B cells is unclear, although repression of the p53 tumor suppressor is
      thought to play a role. Here, we showed that BCL6 has critical oncogene functions
      that are independent of p53 repression. We found that BCL6 cooperates with
      constitutive CD40 signaling to rapidly transform p53-deficient primary mouse B
      cells in vitro. Constitutive CD40 signaling alone does not transform p53
      deficient B cells, indicating that BCL6 acts specifically as an immortalizing
      oncogene in this system. The BCL6 transformed B cells are polyclonal and form
      polyclonal tumors. At the initiation of the cultures, BCL6 does not significantly
      alter cell cycle progression, but it does promote increased cell survival. Early
      cultures of BCL6-expressing B cells exhibited marked repression of ATR and
      p27kip1 but not other BCL6 target genes, suggesting that the ATR and p27kip1
      genes have key early roles in mediating BCL6 transformation function. BCL6
      transformed cell lines exhibited further decreases of ATR and p27kip1 expression
      plus strong decreases in Blimp1 and PDCD2 expression. Our study provides
      important clues about the critical target genes used by BCL6 to transform primary
      B cells and indicates that the CD40 signaling pathway can collaborate with BCL6
      in the transformation of primary B cells. Thus, our study demonstrates a rapid in
      vitro system to analyze the transformation function of BCL6.

PMID- 19405123
TI  - Treatment of disseminated paraganglioma with gemcitabine and docetaxel.
AB  - A male with metastatic paraganglioma received different chemotherapy regimens and
      14 arterial embolizations with no or short-lasting clinical benefit. He was
      started on gemcitabine and docetaxel and, after two cycles, remission of all
      clinical signs occurred over 2 months. A complete biochemical response was
      achieved and angiographic signs of portal hypertension disappeared. He received
      18 cycles of therapy and no limiting side effects were observed. More than 2
      years after gemcitabine and docetaxel treatment, the patient remains symptom
      free. Gemcitabine and docetaxel could be a potential therapeutic strategy for
      this patient.

PMID- 19405124
TI  - A frequent target of paraproteins in the sera of patients with multiple myeloma
      and MGUS.
AB  - Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS)
      and multiple myeloma (MM) paraproteins might play a role in the pathogenesis of
      these neoplasms. We screened a human fetal brain-derived macroarray with the IgA
      or IgG containing sera of 192 consecutive MGUS and MM patients. Twenty-nine of
      192 (15.1%) paraproteins reacted with paratarg-7, a protein of unknown function
      which is expressed in all human tissues. Paratarg-7 reactivity was similarly
      frequent among IgA and IgG paraproteins, but all paratarg-7 reactive IgG
      paraproteins belonged to the IgG3 subtype with 24/57 IgG3 (42.1%) paraproteins
      displaying this specificity. Sequence analysis of paratarg-7 derived from
      patients having a paraprotein with specificity for paratarg-7 revealed no
      differences to paratarg-7 derived from patients with paraproteins of other
      specificities or healthy controls, excluding mutations or polymorphisms as a
      reason for its autoimmunogenicity. Similarly, Western-blot analysis showed
      identical bands for paratarg-7 derived from patients and controls. The above
      random frequency of paratarg-7 as a paraprotein target suggests that paratarg-7
      might be involved in the development of the respective clonal proliferations. The
      identification of paratarg-7 as an antigenic target enables the more detailed
      analysis of tumor-host interactions in these patients and their role in the
      pathogenesis of MM and MGUS.

PMID- 19405125
TI  - MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and
      to glioblastoma outcome.
AB  - The human telomerase reverse transcriptase (hTERT) gene is upregulated in a
      majority of malignant tumours. A variable tandem repeat, MNS16A, has been
      reported to be of functional significance for hTERT expression. Published data on
      the clinical relevance of MNS16A variants in brain tumours have been
      contradictory. The present population-based study in the Nordic countries and the
      United Kingdom evaluated brain-tumour risk and survival in relation to MNS16A
      minisatellite variants in 648 glioma cases, 473 meningioma cases and 1,359 age,
      sex and geographically matched controls. By PCR-based genotyping all study
      subjects with fragments of 240 or 271 bp were judged as having short (S) alleles
      and subjects with 299 or 331 bp fragments as having long (L) alleles. Relative
      risk of glioma or meningioma was estimated with logistic regression adjusting for
      age, sex and country. Overall survival was analysed using Kaplan-Meier estimates
      and equality of survival distributions using the log-rank test and Cox
      proportional hazard ratios. The MNS16A genotype was not associated with risk of
      occurrence of glioma, glioblastoma (GBM) or meningioma. For GBM there were median
      survivals of 15.3, 11.0 and 10.7 months for the LL, LS and SS genotypes,
      respectively; the hazard ratio for having the LS genotype compared with the LL
      was significantly increased HR 2.44 (1.56-3.82) and having the SS genotype versus
      the LL was nonsignificantly increased HR 1.46 (0.81-2.61). When comparing the LL
      versus having one of the potentially functional variants LS and SS, the HR was
      2.10 (1.41-3.1). However, functionality was not supported as there was no trend
      towards increasing HR with number of S alleles. Collected data from our and
      previous studies regarding both risk and survival for the MNS16A genotypes are
      contradictory and warrant further investigations.

PMID- 19405126
TI  - Copy number gain and oncogenic activity of YWHAZ/14-3-3zeta in head and neck
      squamous cell carcinoma.
AB  - Gene amplification, a common mechanism for oncogene activation in cancers, has
      been used in the discovery of novel oncogenes. Low-level copy number gains are
      frequently observed in head and neck squamous cell carcinomas (HNSCCs) where
      numerous amplification events and potential oncogenes have already been reported.
      Recently, we applied restriction landmark genome scanning to study gene
      amplifications in HNSCC and located novel and uncharacterized regions in primary
      tumor samples. Gain on chromosome 8q22.3, the location of YWHAZ (14-3-3zeta), is
      found in 30-40% HNSCC cases. Data obtained from fluorescence in situ
      hybridization and immunohistochemistry on HNSCC tissue microarrays confirmed
      frequent low-level YWHAZ copy number gain and protein overexpression. YWHAZ mRNA
      was frequently upregulated in patients' tumor tissues. Furthermore, YWHAZ RNAi
      significantly suppressed the growth rate of HNSCC cell lines, and overexpression
      of YWHAZ in HaCaT immortalized human skin keratinocytes promotes overgrowth, as
      well as morphological changes. Reduced YWHAZ levels increased the G1/G0-phase
      proportion, decreased the S-phase proportion and the rate of DNA synthesis. Based
      on this evidence, we suggest that YWHAZ is a candidate proto-oncogene and
      deserves further investigation into its role in HNSCC carcinogenesis.

PMID- 19405127
TI  - Identification and characterization of a novel germline p53 mutation in a patient
      with glioblastoma and colon cancer.
AB  - Germline mutations in the p53 tumor suppressor gene have been identified in
      patients with Li-Fraumeni syndrome (LFS) and patients with Li-Fraumeni-like
      syndrome (LFL). However, to date, germline p53 mutations in patients not
      fulfilling the criteria of LFS or LFL have been reported only very rarely. In our
      study, a novel germline c.584T>C (p.Ile195Thr) mutation of the p53 gene was found
      in a 21-year-old male with a glioblastoma and colon cancer. He had no family
      history of cancer within second-degree relatives, and loss of the wild-type p53
      allele and overexpression of p53 protein were observed in both tumors. Functional
      analyses revealed transactivation and growth suppressive function activities of
      the Thr195-type p53 to be impaired. These results suggest germline p53 mutations
      to possibly be responsible for a subset of young adult patient with multiple
      malignant tumors, even those not meeting the clinical criteria for LFS or LFL.

PMID- 19405128
TI  - Mitochondrial inhibitor 3-nitroproprionic acid enhances oxidative modification of
      alpha-synuclein in a transgenic mouse model of multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a progressive neurodegenerative disease
      characterized by autonomic failure, parkinsonism, cerebellar ataxia, and
      oligodendrocytic accumulation of alpha-synuclein (alphasyn). Oxidative stress has
      been linked to neuronal death in MSA and the mitochondrial toxin 3-nitropropionic
      acid (3NP) is known to enhance the motor deficits and neurodegeneration in
      transgenic mice models of MSA. However, the effect of 3NP administration on
      alphasyn itself has not been studied. In this context, we examined the
      neuropathological effects of 3NP administration in alphasyn transgenic mice
      expressing human alphasyn (halphasyn) under the control of the myelin basic
      protein (MBP) promoter and the effect of this administration on posttranslational
      modifications of alphasyn, on levels of total alphasyn, and on its solubility. We
      demonstrate that 3NP administration altered levels of nitrated and oxidized
      alphasyn in the MBP-halphasyn tg while not affecting global levels of
      phosphorylated or total alphasyn. 3NP administration also exaggerated
      neurological deficits in the MBP-halphasyn tg mice, resulting in widespread
      neuronal degeneration and behavioral impairment.

PMID- 19405129
TI  - Fully-automated, multi-stage hippocampus mapping in very mild Alzheimer disease.
AB  - Landmark-based high-dimensional diffeomorphic maps of the hippocampus (although
      accurate) is highly-dependent on rater's anatomic knowledge of the hippocampus in
      the magnetic resonance images. It is therefore vulnerable to rater drift and
      errors if substantial amount of effort is not spent on quality assurance,
      training, and re-training. A fully-automated, FreeSurfer-initialized large
      deformation diffeomorphic metric mapping procedure of small brain substructures,
      including the hippocampus, has been previously developed and validated in small
      samples. In this report, we demonstrate that this fully-automated pipeline can be
      used in place of the landmark-based procedure in a large-sample clinical study to
      produce similar statistical outcomes. Some direct comparisons of the two
      procedures are also presented.

PMID- 19405130
TI  - A single-trace dual-process model of episodic memory: a novel computational
      account of familiarity and recollection.
AB  - Dual-process theories of episodic memory state that retrieval is contingent on
      two independent processes: familiarity (providing a sense of oldness) and
      recollection (recovering events and their context). A variety of studies have
      reported distinct neural signatures for familiarity and recollection, supporting
      dual-process theory. One outstanding question is whether these signatures reflect
      the activation of distinct memory traces or the operation of different retrieval
      mechanisms on a single memory trace. We present a computational model that uses a
      single neuronal network to store memory traces, but two distinct and independent
      retrieval processes access the memory. The model is capable of performing
      familiarity and recollection-based discrimination between old and new patterns,
      demonstrating that dual-process models need not to rely on multiple independent
      memory traces, but can use a single trace. Importantly, our putative familiarity
      and recollection processes exhibit distinct characteristics analogous to those
      found in empirical data; they diverge in capacity and sensitivity to sparse and
      correlated patterns, exhibit distinct ROC curves, and account for performance on
      both item and associative recognition tests. The demonstration that a single
      trace, dual-process model can account for a range of empirical findings
      highlights the importance of distinguishing between neuronal processes and the
      neuronal representations on which they operate.

PMID- 19405131
TI  - Automated segmentation of hippocampal subfields from ultra-high resolution in
      vivo MRI.
AB  - Recent developments in MRI data acquisition technology are starting to yield
      images that show anatomical features of the hippocampal formation at an
      unprecedented level of detail, providing the basis for hippocampal subfield
      measurement. However, a fundamental bottleneck in MRI studies of the hippocampus
      at the subfield level is that they currently depend on manual segmentation, a
      laborious process that severely limits the amount of data that can be analyzed.
      In this article, we present a computational method for segmenting the hippocampal
      subfields in ultra-high resolution MRI data in a fully automated fashion. Using
      Bayesian inference, we use a statistical model of image formation around the
      hippocampal area to obtain automated segmentations. We validate the proposed
      technique by comparing its segmentations to corresponding manual delineations in
      ultra-high resolution MRI scans of 10 individuals, and show that automated volume
      measurements of the larger subfields correlate well with manual volume estimates.
      Unlike manual segmentations, our automated technique is fully reproducible, and
      fast enough to enable routine analysis of the hippocampal subfields in large
      imaging studies.

PMID- 19405132
TI  - Selective effect of age, Apo e4, and Alzheimer's disease on hippocampal
      subfields.
AB  - Histopathological studies and animal models suggest that different physiological
      and pathophysiological processes exert different subfield specific effects on the
      hippocampus. High-resolution images at 4T depict details of the internal
      structure of the hippocampus allowing for in vivo volumetry of hippocampal
      subfields. The aims of this study were (1) to determine patterns of hippocampal
      subfield volume loss due to normal aging and Apo e4 carrier state, (2) to
      determine subfield specific volume losses due to preclinical (MCI) and clinical
      Alzheimer's disease (AD) and their modification due to age and Apo e4 carrier
      state. One hundred fifty seven subjects (119 cognitively healthy elderly
      controls, 20 MCI and 18 AD) were studied with a high resolution T2 weighted
      imaging sequence obtained at 4T aimed at the hippocampus. Apo e4 carrier state
      was known in 95 subjects (66 controls, 14 MCI, 15 AD). Subiculum (SUB), CA1, CA1
      CA2 transition zone (CA1-2 transition), CA3- dentate gyrus (CA3&DG) were manually
      marked. Multiple linear regression analysis was used to test for effects of age,
      Apo e4 carrier state and effects of MCI and AD on different hippocampal
      subfields. Age had a significant negative effect on CA1 and CA3&DG volumes in
      controls (P < 0.05). AD had significantly smaller volumes of SUB, CA1, CA1-2
      transition, and MCI had smaller CA1-2 transition volumes than controls (P <
      0.05). Apo e4 carrier state was associated with volume loss in CA3&DG compared to
      non-Apo e4 carriers in healthy controls and AD. Based on these findings, we
      conclude that subfield volumetry provides regional selective information that
      allows to distinguish between different normal and pathological processes
      affecting the hippocampus and thus for an improved differential diagnosis of
      neurodegenerative diseases affecting the hippocampus.

PMID- 19405133
TI  - Survival outcome in childhood ALL: experience from a tertiary care centre in
      North India.
AB  - BACKGROUND: Survival of children with ALL, in developing nations has not kept
      pace with cure rates in developed countries. Our study was designed to assess
      survival data and identify risk factors. PROCEDURE: Data of 762 patients with ALL
      were analyzed. Information regarding the clinical-demographic profile, therapy
      and course of illness were recorded. Status and duration at last follow-up were
      utilized to generate Kaplan-Meier survival curves. RESULTS: The mean age was 5.7
      +/- 0.23 years (M/F, 3.2:1). Parents of 230 (30.2%) patients opted for no
      therapy. There were 68 and 60 deaths in induction and remission phases
      respectively. Besides these, 111 children either defaulted therapy or were lost
      to follow up. Relapsed disease was documented in 125 cases. The 5-year OS and EFS
      was 46% and 43% respectively. Survival analysis, using the Cox multivariate
      regression, for gender (P = 0.659, CI: 0.852-1.161), age (P = 0.943, CI: 0.725
      1.225), symptom-diagnosis interval (P = 0.002, CI: 1.116-1.668), WCC (P < 0.001,
      CI: 1.353-1.814) and platelet count (P = 0.001, CI: 0.546-0.849) was performed.
      Bulk disease (P = 0.049, CI: 0.428-0.986), mediastinal adenopathy (P = 0.045, CI:
      1.040-3.697), WCC (P = 0.016, CI: 1.395-2.691), platelet count (P = 0.031, CI:
      0.431-0.967) and administration of 2 intensification blocks (P = 0.012, CI: 0.624
      0.940) were found to be significant predictors of outcome by multivariate
      analysis. CONCLUSIONS: The management of ALL requires financial resources and
      access to quality supportive care. One third of our patients opted for no
      therapy. The other problem areas were a high proportion of therapy defaulters,
      lost to follow up and infection related deaths during induction and remission
      phases. The introduction of remedial measures for resolving the difficulties
      identified would hopefully improve cure rates in ALL in developing nations.

PMID- 19405134
TI  - Hematological responses of the grey carpet shark (Chiloscyllium punctatum) and
      the epaulette shark (Hemiscyllium ocellatum) to anoxia and re-oxygenation.
AB  - We compared the hematological responses of wild and captive populations of two
      closely related sharks to a standardized anoxic challenge and during a 12 hr
      recovery period in normoxia: the epaulette shark (Hemiscyllium ocellatum,
      Bonnaterre, 1788) and the grey carpet shark (Chiloscyllium punctatum, Muller and
      Henle, 1838). Compared to normoxic controls, a significant increase in hematocrit
      (captive 22.3%; wild 35.9%) coupled with a decline in mean corpuscular hemoglobin
      concentration occurred in epaulette sharks indicating erythrocyte swelling in
      response to anoxia. However, the grey carpet shark had a significantly increased
      hematocrit (captive 27.2%; wild 29.3%), erythrocyte count (captive 37.6%; wild
      46.3%) and hemoglobin concentration (captive 31.9%; wild 31.5%), suggesting a
      release of erythrocytes into the circulation and/or hemoconcentration in response
      to anoxia. Plasma glucose concentrations were maintained in both wild and captive
      epaulette sharks and in wild grey carpet sharks during anoxia but increased
      significantly after 2 hr of re-oxygenation (epaulette: captive 55.8%; wild 50.1%;
      grey carpet shark: wild 70.3%) and remained elevated for 12 hr. Captive grey
      carpet sharks had an immediate increase in plasma glucose concentrations after
      anoxia (96.4%), which was sustained for 12 hr of re-oxygenation. Lactate
      concentrations significantly increased in captive and wild animals of both
      species after anoxia, reaching a peak at 2 hr of re-oxygenation. Both species
      showed significant, yet divergent, hematological changes in response to anoxia
      and re-oxygenation, which may not only prolong their survival and assist in
      recovery but also reflect their respective ecophysiological adaptations to the
      extreme environments that they inhabit.

PMID- 19405135
TI  - Progressive neurocognitive impairment in young adult survivors of childhood acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Despite the extensive literature on neuropsychological sequelae after
      treatment of childhood acute lymphoblastic leukemia (ALL), the very-long-term
      neurocognitive outcome of the survivors is poorly studied. We assessed
      neuropsychological functioning in a population-based cohort of young adult
      childhood ALL survivors. PROCEDURE: Neuropsychological testing was performed on
      64 survivors an average of 20 years after the diagnosis. The test battery
      included verbal intelligence quotient (VIQ) and performance intelligence quotient
      (PIQ), memory function, orientation and attention as well as motor performance.
      Cranial irradiation had been administered to 44 survivors as part of ALL
      treatment, whereas 20 survivors had been treated solely with chemotherapy. A
      control group consisted of 45 healthy young adults. Earlier neuropsychological
      test results of 45 of the survivors were available for comparison. RESULTS: The
      ALL survivors attained significantly lower test scores than the controls in all
      the neuropsychological function areas. The mean VIQ test scores were 91, 100, and
      109 (P < 0.001), and the mean PIQ test scores 100, 111, and 118 (P < 0.001) for
      the irradiated survivors, non-irradiated survivors and controls, respectively.
      Memory and motor functions were impaired among the irradiated survivor group
      compared with the controls. A significant decline in PIQ and VIQ test scores was
      observed in the irradiated survivor group during the follow-up period, but only
      in VIQ in the non-irradiated group. CONCLUSIONS: Survivors of childhood ALL
      suffer from long-lasting progressive neuropsychological impairment, especially
      when treatment includes cranial irradiation.

PMID- 19405136
TI  - Low-frequency-induced synaptic potentiation: a paradigm shift in the field of
      memory-related plasticity mechanisms?
AB  - Long-term potentiation (LTP) and long-term depression (LTD) are two forms of
      synaptic plasticity thought to play functional roles in learning and memory
      processes. It is generally assumed that the direction of synaptic modifications
      (i.e., up- or down-regulation of synaptic strength) depends on the specific
      pattern of afferent inputs, with high frequency activity or stimulation
      effectively inducing LTP, while low-frequency patterns often elicit LTD. This
      dogma ("high frequency-LTP, low frequency-LTD") has recently been challenged by
      evidence demonstrating low frequency stimulation (LFS)-induced synaptic
      potentiation in the rodent hippocampus and amygdala. Extensive work in the past
      decades has focused on deciphering the mechanisms by which high frequency
      stimulation of afferent fiber systems results in LTP. With this review, we will
      compare and contrast the well-known synaptic and cellular mechanisms underlying
      classical, high-frequency-induced LTP to those mediating the more recently
      discovered phenomena of LFS-induced synaptic enhancement. In addition, we argue
      that LFS protocols provide a means to more accurately mimic some endogenous,
      oscillatory activity patterns present in hippocampal and extra-hippocampal
      (especially neocortical) circuits during periods of memory consolidation.
      Consequently, LFS-induced synaptic potentiation offers a novel and important
      avenue to investigate cellular and systems-level mechanisms mediating the
      encoding, consolidation, and transfer of information throughout multiple
      forebrain networks implicated in learning and memory processes. (c) 2009 Wiley
      Liss, Inc.

PMID- 19405137
TI  - The hippocampus contributes to memory expression during transitive inference in
      mice.
AB  - There is substantial evidence that the hippocampus plays a role in transitive
      inference, the capacity to link overlapping memories and subsequently make novel
      judgments between elements of those memories that are only indirectly related.
      However, it is unclear whether the hippocampus is involved primarily during the
      original acquisition of the overlapping memories, or additionally during the
      flexible expression of those memories during transitive judgments. Here, we
      demonstrated that selective hippocampal damage produced after acquisition of the
      overlapping memories resulted in a severe impairment in subsequent transitive
      inference judgments, indicating that the hippocampus does play an important role
      beyond the initial learning phase. Furthermore, this study extends to mice a role
      for the hippocampus in transitive inference, as previously observed in other
      species.

PMID- 19405138
TI  - Lactic acidosis and hypoglycemia with ALL relapse following engrafted bone marrow
      transplant.
AB  - Lactic acidosis together with hypoglycemia in the face of hematologic malignancy
      is a grave development. A 7-year-old male with pre-B-cell ALL following
      hematopoietic cell transplant was admitted to our hospital in his second relapse.
      On hospital days 4 and 5, he developed refractory hypoglycemia, lactic acidosis,
      central respiratory failure, and acute renal failure. Bicarbonate infusion, B
      vitamins, and hemodialysis were not effective. Care was withdrawn on hospital day
      9. Further understanding of the mechanisms that cause the combined onset of
      lactic acidosis and hypoglycemia will help clinicians in implementing timely
      therapies that may reduce mortality.

PMID- 19405139
TI  - Initial presentation of unscreened children with sickle cell disease: the Toronto
      experience.
AB  - BACKGROUND: The morbidity and mortality related to sickle cell disease (SCD) has
      decreased since the introduction of newborn screening in the United States. Given
      the multicultural nature of the Canadian population and the growing African
      Canadian population, it is concerning that there is no national neonatal
      screening program for SCD in Canada. The objective of this study was to evaluate
      the most common manner in which SCD is diagnosed in children when neonatal
      screening is not available routinely. PROCEDURE: The study design was a
      retrospective chart review. All children aged from birth to 18 years with SCD and
      an admission to the Hospital for Sick Children in Toronto, Canada, between 1978
      and 2004 were eligible for inclusion. RESULTS: Fifty-two percent of the children
      with SCD were diagnosed through some form of screening while 48% were diagnosed
      with symptoms suggestive of their disease. The median age at time of diagnosis
      was 0.75 years in the "screened" group, and 2 years in the "symptom" group (P <
      0.05). The most common symptomatic presentation was with a vaso-occlusive crisis.
      Fifteen percent presented with more severe symptoms including acute chest
      syndrome (5.5%), acute splenic sequestration (5%), sepsis (3.3%), aplastic crisis
      (1%), priapism (0.5%), meningitis (0.5%), stroke (0.5%), and death (1%).
      CONCLUSIONS: Fifteen percent of children with undiagnosed SCD presented initially
      with severe complications of the disease. The morbidity and mortality related to
      undiagnosed SCD underscores the need for a national neonatal screening program in
      Canada.

PMID- 19405140
TI  - Neonatal acute myeloid leukemia in an infant whose mother was exposed to
      diethylstilboestrol in utero.
AB  - We report on an acute myeloid leukemia in a neonate whose mother was exposed to
      diethylstilboestrol in utero. The newborn presented with leukemia cutis,
      hemorrhagic skin lesions, hyperleucocytosis and disseminated intravascular
      coagulation. A bone marrow examination confirmed the diagnosis of acute monocytic
      leukemia with a t(11;19) MLL-ELL fusion transcript. Chemotherapy was initiated
      but the child developed a bilateral pulmonary infection that led to fatal
      respiratory distress. This case shows acute myeloid leukemia and the third
      pediatric leukemia reported after maternal diethylstilboestrol exposure.

PMID- 19405141
TI  - Clinical course and outcome in children with acute lymphoblastic leukemia and
      asparaginase-associated pancreatitis.
AB  - BACKGROUND: Asparaginase, an agent used in the treatment of acute lymphoblastic
      leukemia (ALL), is associated with the development of pancreatitis. The clinical
      course and long-term outcome of patients experiencing this complication has not
      been extensively detailed. PROCEDURE: We reviewed the clinical course for all
      children with ALL diagnosed with pancreatitis at the Dana-Farber Cancer
      Institute/Children's Hospital Boston between 1987 and 2003. The outcome of these
      patients was compared with that of patients with ALL who did not experience
      pancreatitis. RESULTS: Twenty-eight of 403 children (7%) were diagnosed with
      pancreatitis. Patients 10-18 years old at diagnosis had 2.4 times the risk of
      developing pancreatitis compared with younger patients. Pancreatitis typically
      occurred early in the course of therapy (median 4 weeks after first dose of
      asparaginase). Ninety-three percent of affected patients were hospitalized and
      57% received parenteral nutrition. No patient developed chronic sequelae or died
      as a result of pancreatitis. Sixteen (57%) patients were re-treated with
      asparaginase, 10 of whom had another episode of pancreatitis. No significant
      differences in event-free survival were observed when comparing patients with and
      without a history of pancreatitis. CONCLUSION: Asparaginase-associated
      pancreatitis was more common in older children, and caused significant acute
      morbidity. It tended to occur after the first few doses of asparaginase,
      suggesting a predisposition to this complication rather than a cumulative drug
      effect. Re-treatment with asparaginase after an episode of pancreatitis was
      associated with a high risk of recurrent pancreatitis.

PMID- 19405142
TI  - Move it or lose it--is stimulation of the vestibular system necessary for normal
      spatial memory?
AB  - Studies in both experimental animals and human patients have demonstrated that
      peripheral vestibular lesions, especially bilateral lesions, are associated with
      spatial memory impairment that is long-lasting and may even be permanent.
      Electrophysiological evidence from animals indicates that bilateral vestibular
      loss causes place cells and theta activity to become dysfunctional; the most
      recent human evidence suggests that the hippocampus may cause atrophy in patients
      with bilateral vestibular lesions. Taken together, these studies suggest that
      self-motion information provided by the vestibular system is important for the
      development of spatial memory by areas of the brain such as the hippocampus, and
      when it is lost, spatial memory is impaired. This naturally suggests the converse
      possibility that activation of the vestibular system may enhance memory.
      Surprisingly, there is some human evidence that this may be the case. This review
      considers the relationship between the vestibular system and memory and suggests
      that the evolutionary age of this primitive sensory system as well as how it
      detects self-motion (i.e., detection of acceleration vs. velocity) may be the
      reasons for its unique contribution to spatial memory.

PMID- 19405144
TI  - New frontiers in computational analysis of human hippocampal anatomy.

PMID- 19405143
TI  - Prolonged voluntary wheel-running stimulates neural precursors in the hippocampus
      and forebrain of adult CD1 mice.
AB  - Voluntary wheel-running induces a rapid increase in proliferation and
      neurogenesis by neural precursors present in the adult rodent hippocampus. In
      contrast, the responses of hippocampal and other central nervous system neural
      precursors following longer periods of voluntary physical activity are unclear
      and are an issue of potential relevance to physical rehabilitation programs. We
      investigated the effects of a prolonged, 6-week voluntary wheel-running paradigm
      on neural precursors of the CD1 mouse hippocampus and forebrain. Examination of
      the hippocampus following 6 weeks of running revealed two to three times as many
      newly born neurons and 60% more proliferating cells when compared with standard
      housed control mice. Among running mice, the number of newly born neurons
      correlated with the total running distance. To establish the effects of wheel
      running on hippocampal precursors dividing during later stages of the prolonged
      running regime, BrdU was administered after 3 weeks of running and the BrdU
      retaining cells were analyzed 18 days later. Quantifications revealed that the
      effects of wheel-running were maintained in late-stage proliferating cells, as
      running mice had two to three times as many BrdU-retaining cells within the
      hippocampal dentate gyrus, and these yielded greater proportions of both mature
      neurons and proliferative cells. The effects of prolonged wheel-running were also
      detected beyond the hippocampus. Unlike short-term wheel-running, prolonged wheel
      running was associated with higher numbers of proliferating cells within the
      ventral forebrain subventricular region, a site of age-associated decreases in
      neural precursor proliferation and neurogenesis. Collectively, these findings
      indicate that (i) prolonged voluntary wheel-running maintains an increased level
      of hippocampal neurogenesis whose magnitude is linked to total running
      performance, and (ii) that it influences multiple neural precursor populations of
      the adult mouse brain.

PMID- 19405145
TI  - Clinical application of measurement of hippocampal atrophy in degenerative
      dementias.
AB  - Hippocampal atrophy is a characteristic and early feature of Alzheimer's disease.
      Volumetry of the hippocampus using T1-weighted magnetic resonance imaging (MRI)
      has been used not only to assess hippocampal involvement in different
      neurodegenerative diseases as a potential diagnostic biomarker, but also to
      understand the natural history of diseases, and to track changes in volume over
      time. Assessing change in structure circumvents issues surrounding
      interindividual variability and allows assessment of disease progression. Disease
      modifying effects of putative therapies are important to assess in clinical
      trials and are difficult using clinical scales. As a result, there is increasing
      use of serial MRI in trials to detect potential slowing of atrophy rates as an
      outcome measure. Automated and yet reliable methods of quantifying such change in
      the hippocampus would therefore be very valuable. Algorithms capable of measuring
      such changes automatically have been developed and may be applicable to predict
      decline to a diagnosis of dementia in the future. This article details the
      progress in using MRI to understand hippocampal changes in the degenerative
      dementias and also describes attempts to automate hippocampal segmentation in
      these diseases.

PMID- 19405146
TI  - Parametric surface modeling and registration for comparison of manual and
      automated segmentation of the hippocampus.
AB  - Accurate and efficient segmentation of the hippocampus from brain images is a
      challenging issue. Although experienced anatomic tracers can be reliable, manual
      segmentation is a time consuming process and may not be feasible for large-scale
      neuroimaging studies. In this article, we compare an automated method, FreeSurfer
      (V4), with a published manual protocol on the determination of hippocampal
      boundaries from magnetic resonance imaging scans, using data from an existing
      mild cognitive impairment/Alzheimer's disease cohort. To perform the comparison,
      we develop an enhanced spherical harmonic processing framework to model and
      register these hippocampal traces. The framework treats the two hippocampi as a
      single geometric configuration and extracts the positional, orientation, and
      shape variables in a multiobject setting. We apply this framework to register
      manual tracing and FreeSurfer results together and the two methods show stronger
      agreement on position and orientation than shape measures. Work is in progress to
      examine a refined FreeSurfer segmentation strategy and an improved agreement on
      shape features is expected.

PMID- 19405148
TI  - The role of medial temporal lobe in retrieving spatial and nonspatial relations
      from episodic and semantic memory.
AB  - This study examined the involvement of medial temporal lobe, especially the
      hippocampus, in processing spatial and nonspatial relations using episodic and
      semantic versions of a relational judgment task. Participants studied object
      arrays and were tested on different types of relations between pairs of objects.
      Three prevalent views of hippocampal function were considered. Cognitive map
      theory (O'Keefe and Nadel (1978) The Hippocampus as a Cognitive Map. USA: Oxford
      University Press) emphasizes hippocampal involvement in spatial relational tasks.
      Multiple trace theory (Nadel and Moscovitch (1997) Memory consolidation,
      retrograde amnesia and the hippocampal complex Curr Opin Neurobiol 7:217-227)
      emphasizes hippocampal involvement in episodic tasks. Eichenbaum and Cohen's
      ((2001) From Conditioning to Conscious Recollection: Memory Systems of the Brain.
      USA: Oxford University Press) relational theory predicts equivalent hippocampal
      involvement in all relational tasks within both semantic and episodic memory. The
      fMRI results provided partial support for all three theories, though none of them
      fit the data perfectly. We observed hippocampal activation during all relational
      tasks, with increased activation for spatial compared to nonspatial relations,
      and for episodic compared to semantic relations. The placement of activation
      along the anterior-posterior axis of the hippocampus also differentiated the
      conditions. We suggest a view of hippocampal function in memory that incorporates
      aspects of all three theories.

PMID- 19405147
TI  - Oxidative stress status and RNA expression in hippocampus of an animal model of
      Alzheimer's disease after chronic exposure to aluminum.
AB  - It is well established that aluminum (Al) is a neurotoxic agent that induces the
      production of free radicals in brain. Accumulation of free radicals may cause
      degenerative events of aging such as Alzheimer's disease. On the other hand,
      melatonin (Mel) is a known antioxidant, which can directly act as free radical
      scavenger, or indirectly by inducing the expression of some genes linked to the
      antioxidant defense. In this study, AbetaPP female transgenic (Tg2576) (Tg) and
      wild-type mice (5 months of age) were fed with Al lactate supplemented in the
      diet (1 mg Al/g diet). Simultaneously, animals received oral Mel (10 mg/kg)
      dissolved in tap water until the end of the study at 11 months of age. Four
      treatment groups were included for both Tg and wild-type mice: control, Al only,
      Mel only, and Al+Mel. At the end of the period of treatment, hippocampus was
      removed and processed to examine the following oxidative stress markers: reduced
      glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD),
      glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and
      thiobarbituric acid reactive substances (TBARS). Moreover, the gene expression of
      Cu-ZnSOD, GR, and CAT was evaluated by real-time RT-PCR. Aluminum concentration
      in hippocampus was also determined. The biochemical changes observed in this
      tissue suggest that Al acts as a pro-oxidant agent. Melatonin exerts an
      antioxidant action by increasing the mRNA levels of the antioxidant enzymes SOD,
      CAT, and GR evaluated in presence of Al and Mel, with independence of the animal
      model.

PMID- 19405149
TI  - gammaH2AX marks the main events of the spermatogenic process.
AB  - Recent findings reveal that chromatin reorganization requires formation and
      repair of DNA double strand breaks (DSBs). Therefore, dynamic changes in
      chromatin structure taking place along the mitotic and the meiotic processes
      should be accompanied by histone H2AX phosphorylation and formation of gamma
      H2AX, a prominent event occurring at DSB sites. Accordingly, gamma H2AX has been
      detected at multiple developmental steps in adult germ cells. Nevertheless, no
      comprehensive study focusing on the main biological events occurring in the
      seminiferous epithelium has been carried out in mammals. Here I analyze H2AX
      phosphorylation in immunostained testis sections comparing PAS/cresyl violet
      counterstained, noncounterstained, and immuno-fluorescence preparations and show
      several waves of H2AX phosphorylation/dephosphorylation coupled to various
      developmental phases of spermatogonia and spermatocytes as well as to spermatid
      differentiation. The combined detection of DNA replication or free 3'-OH DNA ends
      highlight the possible significance of gamma H2AX at these locations.

PMID- 19405150
TI  - Mice lacking adenylyl cyclase-5 cope badly with repeated restraint stress.
AB  - Physiological responses to acute stress proceed with the activation of the
      hypothalamus-pituitary-adrenal gland (HPA) system. Many brain regions are known
      to modulate the HPA axis activation in stress responses, but the detailed neural
      circuits and signaling system in the upstream of the HPA axis have to be explored
      further. Type 5 adenylyl cyclase (AC5) is highly concentrated in the dorsal
      striatum and nucleus accumbens, which are implicated in reward and stress-related
      behavior. AC5(-/-) mice exposed to daily 2-hr restraint stress for only 3-5 days
      showed poor stress-coping responses, including severe body weight loss, poor coat
      condition, respiratory difficulties, and freezing behavior. Plasma corticosterone
      levels during 2-hr stress sessions increased in AC5(-/-) mice compared with those
      of AC5(+/+) mice. However, neither the corticosterone receptor antagonist RU486
      nor the CRH receptor antagonist NBI27914 blocked their poor stress coping,
      whereas the administration of the GABA(A) receptor allosteric modulator diazepam
      or the D1 dopamine receptor antagonist SCH23390 prior to restraint stress
      sessions changed their stress-coping response to the stressed AC5(+/+) mouse
      level. Stress-triggered c-Fos expression was completely blunted in the dorsal
      striatum of AC5(-/-). These results suggest that the AC5-associated signal system
      and neural network are involved in the regulation of anxiety and stress-coping
      response.

PMID- 19405151
TI  - Physiological responses of CHO cells to repetitive hydrodynamic stress.
AB  - A majority of the previous investigations on the hydrodynamic sensitivity of
      mammalian cells have focused on lethal effects as determined by cell death or
      lysis. In this study, we investigated the effect of hydrodynamic stress on CHO
      cells in a fed-batch process using a previously reported system which subjects
      cells to repetitive, high levels of hydrodynamic stress, quantified by energy
      dissipation rate (EDR). The results indicated that cell growth and monoclonal
      antibody production of the test cells were very resistant to the hydrodynamic
      stress. Compared to the control, no significant variation was observed at the
      highest EDR tested, 6.4 x 10(6) W/m(3). Most product quality attributes were not
      affected by intense hydrodynamic stress either. The only significant impact was
      on glycosylation. A shift of glycosylation pattern was observed at EDR levels at
      or higher than 6.0 x 10(4) W/m(3), which is two orders of magnitude lower than
      the EDR where physical cell damage, as measured by lactate dehydrogenase release,
      was observed. While not as extensively investigated, a second monoclonal antibody
      produced in a different CHO clone exhibited the same glycosylation change at an
      intensive EDR, 2.9 x 10(5) W/m(3). Conversely, a low EDR of 0.9 x 10(2) W/m(3)
      had no effect on the glycosylation pattern. As 6.0 x 10(4) W/m(3), the lowest EDR
      that triggers the glycosylation shift, is about one order of magnitude higher
      than the estimated, maximum EDR in typically operated, large-scale stirred tank
      bioreactors, further studies in a lower EDR range of 1 x 10(3)-6.0 x 10(4) W/m(3)
      are needed to assess the glycosylation shift effect under typical large-scale
      bioreactor operation conditions. Follow-up studies in stirred tanks are also
      needed to confirm the glycosylation shift effect and to validate the repetitive
      hydrodynamic stress model.

PMID- 19405152
TI  - A two-phase partitioning airlift bioreactor for the treatment of BTEX
      contaminated gases.
AB  - This investigation characterizes a novel 11 L airlift two-phase partitioning
      bioreactor (TPPB) for the treatment of gases contaminated with a mixture of
      benzene, toluene, ethylbenzene, and o-xylene (BTEX). The application of the TPPB
      technology in an airlift bioreactor configuration provides a novel technology
      that reduces energy intensity relative to traditional stirred tank TPPB
      configurations. The addition of a solid second phase of silicone rubber beads
      (10%, v/v) or of a liquid second phase of silicone oil (10%, v/v) resulted in
      enhanced performance of the airlift bioreactor relative to the single phase case,
      with 20% more BTEX being removed from the gas phase during an imposed transient
      loading. During a 4 h loading step change of three times the nominal loading (60
      g m(-3) h(-1)), overall removal efficiencies for the airlift TPPBs containing a
      liquid or solid phase remained above 75%, whereas the single phase airlift had an
      overall removal efficiency of 47.1%. The airlift TPPB containing a silicone
      rubber second phase was further characterized by testing performance during
      steady-state operation over a range of loadings and inlet gas flow rates in the
      form of a 3(2) factorial experimental design. Optimal operating conditions that
      avoid oxygen limitations and that still have a slow enough gas flow rate for
      sufficient BTEX transfer from the gas phase to the working volume are identified.
      The novel solid-liquid airlift TPPB reduces energy inputs relative to stirred
      tank designs while being able to eliminate large amounts of BTEX during both
      steady-state and fluctuating loading conditions.

PMID- 19405153
TI  - Characterization of cryogel monoliths for extraction of minor proteins from milk
      by cation exchange.
AB  - Extraction and purification of high-value minor proteins directly from milk
      without pre-treatment is a challenge for the dairy industry. Pre-treatment of
      milk before extraction of proteins by conventional packed-bed chromatography is
      usually necessary to prevent column blockage but it requires several steps that
      result in significant loss of yield and activity for many minor proteins. In this
      paper, we demonstrate that it is possible to pass 40-50 column volumes of various
      milk samples (raw whole milk, homogenized milk, skim milk and acid whey) through
      a 5 mL cryogel chromatographic column at 550 cm/h without exceeding its pressure
      limits if the processing temperature is maintained above 35 degrees C. The
      dynamic binding capacity obtained for the cryogel matrix (2.1 mg/mL) was similar
      to that of the binding capacity (2.01 mg/mL) at equilibrium with 0.1 mg/mL of
      lactoferrin in the feed samples. The cryogel column selectively binds lactoferrin
      and lactoperoxidase with only minor leakage in flowthrough fractions. Lactoferrin
      was recovered from elution fractions with a yield of over 85% and a purity of
      more than 90%. These results, together with the ease of manufacture, low cost and
      versatile surface chemistry of cryogels suggest that they may be a good
      alternative to packed-bed chromatography for direct capture of proteins from
      milk.

PMID- 19405154
TI  - Gene-expression-based quality scores indicate optimal harvest point in Bordetella
      pertussis cultivation for vaccine production.
AB  - The evolution of vaccine product quality during batch cultivation of Bordetella
      pertussis, the causative agent of whooping cough, was investigated with the goal
      to determine the optimal harvest point. The process was explored by measuring
      mRNA expression at frequent intervals during cultivation. The genes that are
      involved in virulence are already known for this product and changes in their
      expression levels are proposed to be indicative for product quality. A
      quantitative product quality score is calculated based on the expression levels
      of these virulence genes, which allows comparison of expected product quality
      between culture samples. Product quality scores were maximal throughout the
      logarithmic growth phase, but dropped significantly at the start of the
      stationary phase. This showed that the decreasing lactate and glutamate
      concentrations towards the end of the batch are critical for product quality. On
      line measurement of these nutrients allows the cultivation process to be
      harvested at the optimal harvest point, increasing process robustness and
      consistency.

PMID- 19405155
TI  - Coronary compression caused by stenting a right pulmonary artery conduit.
AB  - Extrinsic compression of the left main coronary artery is a rare and life
      threatening complication of endovascular stenting of pulmonary artery conduits.
      This case report describes fatal myocardial infarction caused by compression of
      the left main coronary artery due to stent placement in a stenosed right
      pulmonary artery conduit.

PMID- 19405156
TI  - Transapical left ventricular access for difficult to reach interventional targets
      in the left heart.
AB  - OBJECTIVE: Interventional targets may be virtually "excluded" due to vascular
      access problems or complex previous surgical procedures. This study reviews our
      experience using transapical ventricular puncture to gain direct access to the
      systemic ventricle. PATIENTS: Patient 1 (74 years, 2 previous sternotomies),
      patient 2 (66 years, 5 previous sternotomies), and patient 5 (69 years, 3
      previous sternotomies) with prosthetic valves had paravalvular mitral valve
      leaks. Patient 3 (6.3 years, 2 previous sternotomies) with an extracardiac Fontan
      conduit, had a significant residual leak after two previous surgical attempts of
      patch closure of a severely regurgitant right atrioventricular valve. Patient 4
      (10 months) had failure of standard ablation of the posteroseptal region of the
      mitral valve with persistent life-threatening episodes of ventricular
      tachycardia. METHODS: Procedures were performed under general anesthesia. Entry
      site was percutaneous in three patients and in two (and one conversion) a mini
      thoracotomy was used. Sheaths were placed (6 F) using standard Seldinger
      technique, followed by the procedure as required. Direct surgical closure of the
      puncture site was done in 4 patients and in patient 3, a percutaneous vascular
      occlusion device was used. RESULTS: Easy and immediate access was obtained in all
      patients. The paravalvular leaks were crossed within seconds and completely
      closed with Amplatzer occluders. In patient 3 the valve was crossed using a
      Brokenbrough needle and a 12-mm Amplatzer device was placed in the patch leak.
      Patient 4 was successfully ablated using a 7-F irrigated catheter endo- and
      epicardially. Complications were in the percutaneous puncture group: in one
      patient a coronary artery was punctured and in one a hemothorax developed.
      CONCLUSION: Direct left ventricular puncture offers a very useful alternative
      access site in selected patients to reach "inaccessible" targets for certain
      percutaneous interventions in patients where standard approaches may be
      impossible or difficult.

PMID- 19405157
TI  - Percutaneous closure of a postinfarction ventricular septal defect and an
      iatrogenic left ventricular free-wall perforation using two Amplatzer muscular
      VSD occluders.
AB  - A 83-year-old woman underwent percutaneous closure of postinfarction ventricular
      septal defect following anteroseptal myocardial infarction and percutaneous
      coronary intervention with stent implantation of the left anterior descending
      coronary artery. Postinfarction percutaneous ventricular septal defect closure
      was initially complicated by an iatrogenic left ventricular free-wall
      perforation. Both defects were closed using two Amplatzer muscular VSD occluders
      during the same session.

PMID- 19405158
TI  - Novel mobile telemedicine system for real-time transmission of out-of-hospital
      ECG data for ST-elevation myocardial infarction.
AB  - The guidelines recommend routine use of 12-lead electrocardiogram (ECG) and
      advance notification to the emergency department for patients with ST-elevation
      myocardial infarction (STEMI). However, transmission of out-of-hospital 12-lead
      ECG to emergency department is still not widely practiced and ECG interpretation
      before arrival at the emergency department is not established. We have developed
      a novel mobile telemedicine system to transmit real-time 12-lead ECG data between
      moving ambulances and in-hospital physicians in cardiovascular emergency cases.
      When used, this system immediately identifies patients with STEMI and it is
      coupled to a centralized system to alert the cardiac catheterization teams to
      prepare for prompt intervention. This report presents the first case with STEMI
      who was successfully treated using this novel mobile telemedicine system.

PMID- 19405159
TI  - Successful embolization of a left ventricular pseudoaneurysm after perventricular
      ventricular septal defect device closure.
AB  - Perventricular device closure has become an important management adjunct for
      ventricular septal defects deemed inoperable and difficult to address in the
      catheterization laboratory. Complications directly related to the procedure are
      rarely reported, and all have been manifest in the periprocedural period. We
      present the case of a 6-week-old boy who underwent perventricular closure of a
      muscular ventricular septal defect and had a left ventricle pseudoaneurysm
      identified 10 months later during catheterization to close residual septal
      defects. We describe the subsequent percutaneous coil embolization of the
      pseudoaneurysm and clinical follow-up.

PMID- 19405160
TI  - Rebuttal: Guilty thermistors or maybe not?

PMID- 19405161
TI  - Comparing long-term outcomes between drug-eluting and bare-metal stents in the
      treatment of cardiac allograft vasculopathy.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of death
      after the first year following heart transplantation. We compared restenosis
      rates, mortality, and other major adverse cardiac events (MACE) between
      transplant recipients treated with DES and BMS for CAV. METHODS: All patients
      from our heart transplant registry undergoing PCI with stenting for CAV were
      identified. Procedural data, baseline clinical characteristics, yearly coronary
      angiography, cardiac events and death were prospectively collected. Primary
      outcome was in-stent restenosis (ISR). Secondary outcomes were in-segment
      restenosis, target vessel revascularization (TVR), all-cause mortality and
      combined MACE. RESULTS: 36 lesions in 25 patients treated with DES were compared
      with 31 BMS-treated lesions in 19 patients. There were no significant differences
      in baseline characteristics. 12-month incidence of ISR was 0% with DES vs. 12.9%
      with BMS, P = 0.03. Over mean (+/-standard error) follow-up of 51.1 +/- 7.5
      months this difference was significant for vessels < or =3 mm in diameter, hazard
      ratio (HR) DES vs. BMS 0.37 (95% CI 0.11 to 0.95) P = 0.037; but not for vessels
      >3 mm P = 0.45. However, there was no difference in overall longterm patency
      because of similar rates of in-segment restenosis between DES and BMS, HR 1.13
      (95% CI 0.43 to 2.97) P = 0.81. Also, the rates of TVR, death from any cause and
      combined MACE were similar; log rank P 0.88, 0.67, and 0.85, respectively.
      CONCLUSION: This study suggests that after PCI for cardiac allograft
      vasculopathy, despite a lower in-stent restenosis rate in DES compared with BMS,
      in-segment restenosis and clinical cardiac endpoints are similar.

PMID- 19405162
TI  - Experimental evaluation of a new articulated Amplatzer ductal occluder device
      without fabric.
AB  - OBJECTIVES: To describe a new percutaneous PDA device. BACKGROUND: The ADO II was
      developed by AGA Medical for closure of small-moderate sized PDAs via a small
      delivery catheter from an antegrade or retrograde catheter approach. The
      objective of this study was to evaluate the technical feasibility, safety, and
      efficacy of the ADO II in a canine PDA model. METHODS: The ADO-II consists of
      multi-layer nitinol wire braid with symmetric retention disks and an articulating
      connecting center waist, without sewn-in polyester, that can be delivered though
      a 4-5F catheter. A PDA was surgically created in nine dogs. Transcatheter
      occlusion of the PDA was performed using the ADO II. Angiographic and hemodynamic
      data were obtained at 7, 30, 60, and 90 days post-procedure. The devices were
      then harvested for pathology. RESULTS: Devices were placed transarterially (n =
      8) and transvenously (n = 1). All PDAs were occluded and there were no
      significant pressure gradients (P > 0.05) at the immediate and 90 post-implant
      evaluations. Pathology found endothelial coverage on all aortic and pulmonary
      disks, except at the tip of the microscrew. There were no procedural
      complications. One canine was euthanized 4 hr after device implant because of a
      clinical deterioration. The staff veterinarian and pathologist concluded that the
      animal's illness was not device related. CONCLUSIONS: The Amplatzer ADO II
      devices can be safely deployed in animal models of PDAs, with complete resolution
      of the PDA shunt. The lower profile and symmetry of the ADO II allows for venous
      or arterial approach and smaller delivery catheter size. The ADO-II is expected
      to be a preferred alternative for closure of small-moderate PDAs.

PMID- 19405163
TI  - Automated contrast injectors for angiography: devices, methodology, and safety.
AB  - Automated contrast injectors (ACIs) are widely employed in interventional
      cardiology, radiology and neurology. Information regarding the specifications of
      advanced ACIs and the appropriate injection settings of these devices is limited
      in the medical literature. This review describes the specifications of the most
      widely used ACIs and provides appropriate recommendations for injection settings
      for the various angiographic studies. These recommendations are based on expert
      consensus and commercial experience regarding characteristics of devices,
      catheters and contrast. The suggested settings were not subject to rigorous
      comparative clinical assessment. This review should increase the familiarity,
      comfort and appreciation of safety among ACI users.

PMID- 19405165
TI  - Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor
      dependent mechanism.
AB  - BACKGROUND: Classical effects of oestrogen involve activation of target genes
      after binding nuclear receptors. Oestrogenic effects too rapid for DNA
      transcription (non-genomic) are known to occur. The effect of oestrogen on
      colonic motility is unknown despite the prevalence of gastrointestinal symptoms
      in pregnant and premenopausal women. METHODS: Histologically normal colon was
      obtained from proximal resection margins of colorectal carcinoma specimens.
      Circular smooth muscle strips were microdissected and suspended in organ baths
      under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol
      (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8).
      Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8).
      Other strips were exposed to calphostin C or cycloheximide. Carbachol was added
      in increasing concentrations and contractile activity was recorded isometrically.
      RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per
      cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action,
      the effect was apparent within minutes and reversible. It was observed with both
      17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by
      cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor
      mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth
      muscle by a non-genomic mechanism involving cell membrane coupling.

PMID- 19405166
TI  - By the way, doctor.  I have healthy cholesterol levels, but a high triglyceride
      level.  What are triglycerides, and how dangerous is it to have high levels?

PMID- 19405164
TI  - Direct metabolic fingerprinting of commercial herbal tinctures by nuclear
      magnetic resonance spectroscopy and mass spectrometry.
AB  - INTRODUCTION: Tinctures are widely used liquid pharmaceutical preparations
      traditionally obtained by maceration of one or more medicinal plants in ethanol
      water solutions. Such a process results in the extraction of virtually hundreds
      of structurally diverse compounds with different polarities. Owing to the large
      chemical diversity of the constituents present in the herbal tinctures, the
      analytical tools used for the quality control of tinctures are usually optimised
      only for the detection of single chemical entities or specific class of
      compounds. OBJECTIVE: In order to overcome the major limitations of the current
      methods used for analysis of tinctures, a new methodological approach based on
      NMR spectroscopy and MS spectrometry has been tested with different commercial
      tinctures. METHODOLOGY: Diffusion-edited 1H-NMR (1D DOSY) and 1H-NMR with
      suppression of the ethanol and water signals have been applied here for the first
      time to the direct analysis of commercial herbal tinctures derived from Echinacea
      purpurea, Hypericum perforatum, Ginkgo biloba and Valeriana officinalis. The
      direct injection of the tinctures in the MS detector in order to obtain the
      corresponding metabolic profiles was also performed. RESULTS: Using both NMR and
      MS methods it was possible, without evaporation or separation steps, to obtain a
      metabolic fingerprint able to distinguish between tinctures prepared with
      different plants. Batch-to-batch homogeneity, as well as degradation after the
      expiry date of a batch, was also investigated. CONCLUSION: The techniques
      proposed here represent fast and convenient direct analyses of medicinal herbal
      tinctures.

PMID- 19405167
TI  - Hormone therapy.  An update on risks and benefits.

PMID- 19405168
TI  - Cardiovascular comorbidities and blood pressure control in  stroke survivors.
AB  - OBJECTIVE: To examine the association of cardiovascular(CV) comorbidities with
      the likelihood of being a stroke survivor and to determine the prevalence,
      treatment, and control of hypertension in this population. METHODS: In the
      National Health and Nutrition Examination Survey from 1999 to 2004, 495 stroke
      survivors, aged 20 years or older, were characterized by CV risk factors and
      comorbidities. Hypertension prevalence, treatment,and control rates were
      determined and logistic regression was performed to examine the likelihood of
      stroke according to the presence of comorbidities. RESULTS: Of the stroke
      survivors, 59.4% were women, 57.1%were at least 65 years of age, 66.2% were
      overweight/obese, 25.1% were current smokers, 75.1% had hypertension, and 79.3%
      had additional comorbidities,including diabetes mellitus (24.7%), coronary artery
      disease(28.8%), chronic kidney disease (25.3%), heart failure(16.5%), and
      peripheral arterial disease (10.9%). The odds(and 95% confidence intervals) of
      prevalent stroke were 2.2(1.5-3.2), 5.0 (3.2-7.8), 4.1 (2.1-7.8), and 10.0 (4.8
      20.9)with one, two, three, and four or more comorbidities,respectively. Of these
      high-risk stroke survivors with comorbidities and hypertension, 18% were not
      receiving antihypertensive therapy; of those receiving therapy, 55.3%did not meet
      a systolic blood pressure goal of less than 140 mmHg and, on average, were 20
      mmHg above this target. CONCLUSION: A high percentage of stroke
      survivors,projected to 4.98 million adults in the USA have multiple CV risk
      factors, numerous comorbidities, and poor control of hypertension, placing them
      at increased risk for further complications. Therefore, increased efforts must be
      made to reduce overall global risk in these high-risk persons.

PMID- 19405169
TI  - Re: JSLS(2008)12:113-116 Postoperative Pain After Laparoscopic Ventral Hernia
      Repair: a prospective comparison of sutures versus tacks.

PMID- 19405170
TI  - Meta-analysis: statistical methods  for binary data pooling.

PMID- 19405171
TI  - Generating tolerogenic dendritic cells with neuropeptides.
AB  - Induction of antigen-specific tolerance is critical to prevent autoimmunity, to
      maintain immune homeostasis, and to achieve transplant tolerance. In addition to
      their classic role as sentinels of the immune response, dendritic cells (DCs)
      play important roles in maintaining peripheral tolerance through the
      induction/activation of regulatory T (Treg) cells. The possibility of generating
      tolerogenic DCs opens new therapeutic perspectives in autoimmune and inflammatory
      diseases. Characterizing endogenous factors that contribute to the development of
      tolerogenic DCs is highly relevant. Some neuropeptides that are produced during
      the ongoing inflammatory response have emerged as endogenous anti-inflammatory
      agents that participate in the regulation of the processes that ensure self
      tolerance. Here, we examine the latest research findings indicating that the role
      of these neuropeptides in immune tolerance is partially mediated through
      differential effects on DC functions, which depend on the differentiation and
      activation states. Importantly, neuropeptides such as vasoactive intestinal
      peptide, pituitary adenylate cyclase-activating polypeptide, and melanocyte
      stimulating hormone have demonstrated an ability to induce tolerogenic DCs with
      the capacity to generate CD4 and CD8 Treg cells. The possibility of generating or
      expanding ex vivo tolerogenic DCs with neuropeptides indicates the therapeutic
      potential for autoimmune diseases and graft-versus-host disease after allogeneic
      transplantation in humans.

PMID- 19405172
TI  - Melanoma vaccines: The problems of local immunosuppression.
AB  - The incidence of cutaneous melanoma in Europe is rising, and the disease is
      incurable once metastases occur. Because melanoma expresses antigens that can be
      specifically recognized by the immune system, and because this disease
      occasionally undergoes spontaneous regression mediated by anti-tumor immunity, a
      number of different melanoma vaccines have been developed and tested clinically.
      Although most such vaccines show efficacy in vitro and an ability to stimulate
      anti-melanoma immune responses in blood, they have proved disappointing in
      clinical practice. It has become increasingly clear that the interaction between
      melanoma and the immune system is determined locally, within the tumor or
      draining lymph nodes. It is now clear that melanoma cells have the ability to
      anergize the immune system by inducing an immunosuppressive microenvironment that
      may explain the inability of systemic vaccines to alter patient outcomes. This
      subversion of the immune system involves alteration of dendritic cell (DC)
      function by tumor-derived cytokines, leading to the generation of suppressive and
      regulatory T lymphocytes. Successful melanoma vaccination probably requires
      therapeutic neutralization of the immunosuppressive microenvironment, which will
      require greater understanding of the molecular mechanisms used by the tumor to
      promote immunosuppression. Nevertheless, if these problems can be overcome, it
      seems likely that the efficacy of melanoma vaccines could be greatly enhanced.

PMID- 19405173
TI  - Dendritic cell tolerogenicity: a key mechanism in immunomodulation by vitamin D
      receptor agonists.
AB  - Dendritic cells (DC) induce or tolerize T cells, and tolerogenic DCs can promote
      the development of regulatory T cells (Treg) with suppressive activity. Thus, the
      possibility of manipulating DCs and enhancing their tolerogenic properties using
      different pharmacologic or biologic agents could be exploited to control a
      variety of chronic immuno-mediated inflammatory conditions. Among agents able to
      promote induction of tolerogenic DCs, vitamin D receptor (VDR) agonists have
      attracted considerable attention, also because of their potential in clinical
      translation. DCs are key targets for the immunomodulatory effects of VDR
      agonists, which shape DC phenotype and function, enhancing their tolerogenicity
      in adaptive immune responses. Tolerogenic DCs induced by a short treatment with
      VDR agonists promote CD4+CD25+Foxp3+ Treg cells that are able to mediate
      transplantation tolerance and to arrest the development of autoimmune diseases.
      VDR agonists not only favor induction of CD4+CD25+ Treg cells, but can also
      enhance their recruitment at inflammatory sites. The tolerogenic properties
      induced by VDR agonists in DCs, leading to enhanced Treg cell development, likely
      contribute to the beneficial activity of these hormone-like molecules in
      autoimmune disease and graft rejection models, highlighting their applicability
      to the treatment of chronic inflammatory conditions sustained by autoreactive or
      alloreactive immune responses.

PMID- 19405175
TI  - Induction of ILT expression on nonprofessional antigen presenting cells: Clinical
      applications.
AB  - Achieving tolerance toward solid organ allografts remains challenging.
      Nonprofessional antigen-presenting cells, mainly endothelial cells, representing
      the first barrier between the donor organ and the recipient immune system
      represent a promising platform to induce tolerance towards allografts without
      compromising the recipient's immune system. Expression of ILT3 and ILT4, two
      members of the immunoglobulin-like transcript (ILT) family, has been demonstrated
      in endothelial cells in vitro and in vivo resulting in modulated endothelium
      dependent T-cell activation. We here review mechanisms and effects of ILT3/ILT4
      upregulation on endothelial cells and their potential significance in solid organ
      transplantation.

PMID- 19405174
TI  - Expression and function of immunoglobulin-like transcripts on tolerogenic
      dendritic cells.
AB  - The expression of inhibitory immunoglobulin-like transcripts (ILTs) on dendritic
      cells (DCs) is a biomarker of tolerogenic DCs. In this article we discuss current
      knowledge on the function of ILTs and explore the molecular mechanisms involved
      in modulation of DCs via the inhibitory receptor and its natural ligand,
      rendering these cells tolerogenic. We propose a method to enhance targeting of
      inhibitory receptors on DCs using microparticles containing a preferential
      ligand, HLA-G, and monoclonal antibody against the pan-DCs marker CD11c. The
      double-coated microparticles increase the binding of ILT4 receptor and improve
      modulation of DCs in vitro and in vivo. This targeting concept can be used for
      regulation of specific immune responses to antigens in transplantation,
      autoimmunity, allergy, and cancer.

PMID- 19405176
TI  - Function and dysfunction of dendritic cells in autoimmune rheumatic diseases.
AB  - Dendritic cells (DC) have been implicated both in initiation of immunity and in
      immune tolerance. The mechanisms whereby tolerogenic DC may induce and maintain
      peripheral tolerance include the generation or expansion of regulatory T cells
      (Treg) and the promotion of T-cell anergy or deletion. A wide spectrum of
      hematopoietic growth factors and cytokines are endowed with the ability to
      differentiate tolerogenic DC both in vitro and in vivo. Based on this knowledge,
      therapeutic vaccination with cytokine-modulated tolerogenic DC has been applied
      to animal models of autoimmune disorders. This article will review the current
      experimental evidence underpinning DC dysfunction in rheumatic autoimmune
      diseases and will discuss how the manipulation of DC and Treg number and function
      may control undesired T-cell responses.

PMID- 19405177
TI  - Implant stability in relation to   osseointegration: an experimental study   in
      the Labrador dog.
AB  - OBJECTIVE: Resonance frequency analysis (RFA) is supposed to determine implant
      stability. The relation between RFA and the degree of bone-to-implant contact
      (BIC), however, is unclear. The objective of the present experiment was to
      evaluate RFA values in relation to osseointegration. MATERIAL AND METHODS: In 20
      Labrador dogs, all mandibular premolars were extracted bilaterally. After 3
      months, four transmucosal screw-shaped experimental implants were placed in each
      mandibular premolar region. The implants (12 mm length, slashed circle 4.1mm,
      insertion depth 9 mm) were either SLA surface or turned surface implants. The
      animals were divided into four groups (five dogs in each group) to study healing
      following implant installation at 2 h, 4 days, 1, 2, 4, 6, 8 and 12 weeks. Two
      experimental implants of each type were installed in each edentulous premolar
      region. A plaque control program was initiated 2 weeks after each implant
      installation. RFA assessments were performed at the time of implant installation,
      at one to three occasions during the monitoring period and at the termination of
      the experiment. At the end of the experiment, the dogs were sacrificed and each
      implant site was dissected and processed for histological analysis. The results
      of the histological analysis, i.e. marginal bone level, degree of
      osseointegration (BIC%) and bone density, were compared with the corresponding
      Implant Stability Quotient (ISQ) values of the RFA assessment. RESULTS: No
      correlations between histological parameters of osseointegration and ISQ values
      could be identified. Marginal bone level changes, differences in BIC% and bone
      density were not reflected in the RFA at any time-point during the 12-week
      monitoring period. CONCLUSION: The value of RFA to predict implant stability over
      time and to determine at which time-point an implant may be exposed to functional
      load has to be questioned.

PMID- 19405178
TI  - Evaluation of an elderly faller by medical students and rehabilitation residents.
AB  - As part of the development of a curriculum for medical students and
      rehabilitation residents at New York University School of Medicine, an Objective
      Structured Clinical Examination (OSCE) station was developed for formative
      evaluation. The goal was to determine the existing knowledge and competence of
      medical students and rehabilitation residents in the analysis and treatment of a
      geriatric patient with a history of falls. This OSCE station was designed to
      focus on three specific clinical skills needed in assessing the elderly faller.
      The OSCE station was a standardized patient (SP) encounter with a 75-year-old man
      presenting with falls. Seventy-five medical students and 41 rehabilitation
      medicine residents participated in the study. There was high agreement between
      the SP and a geriatric physician used to assess performance on gait (Cronbach
      alpha=0.918) and orthostatic blood pressure (Cronbach alpha=0.887) assessment. Of
      the medical students, 43.5% did not check orthostatic blood pressure, 56.8% did
      not evaluate gait, and 92.0% did not consider assistive device prescription. Only
      20.0% checked both orthostatic blood pressure and gait. Likewise, 73.8% of
      residents did not check orthostatic blood pressure, 38.1% did not evaluate gait
      and 92.9% did not consider assistive device prescription. Only 19.0% checked both
      orthostatic blood pressure and gait. The results of this examination are alarming
      and suggest that education regarding the approach to an elderly person who falls
      is inadequate, leaving students and residents poorly prepared to take care of the
      "silver tsunami."

PMID- 19405179
TI  - Will psychiatry survive in the long-term care setting?

PMID- 19405180
TI  - Plasma homocysteine and cerebrospinal fluid neurodegeneration biomarkers in mild
      cognitive impairment and dementia.

PMID- 19405181
TI  - Apolipoprotein E, dementia, and human longevity.

PMID- 19405182
TI  - In-hospital stroke.

PMID- 19405183
TI  - Feeling tired predicts functional status, physical activity, and mortality in
      elderly people.

PMID- 19405184
TI  - Treatment of pulmonary embolism with low-dose prolonged infusion of tissue-type
      plasminogen activator in an 85-year-old woman.

PMID- 19405185
TI  - Evidence for genetic association between East Asian and western North American 
      Crataegus L. (Rosaceae) and rapid divergence of the eastern North American 
      lineages based on multiple DNA sequences.
AB  - Phylogeographic relationships were constructed for 72 Old and New World Crataegus
      species using combinations of four chloroplast and up to five nuclear regions.
      Maximum parsimony, maximum likelihood, and Bayesian results yield consistent
      relationships among major lineages. The close associations of the East Asian and
      western North American species point toward ancient trans-Beringian migrations.
      Relationships among eastern North American species are poorly resolved and few
      groups are identified that are congruent with existing classifications. Scant
      variation and short internal branches among these species suggest rapid
      divergence associated with polyploidy and hybridization. Incongruence between the
      chloroplast and nuclear data, and morphology suggest hybrid origins of three
      species from an extinct European lineage (the male parent) and three different
      North American female parents. Europe and eastern North America are suggested as
      the most recent common areas for Crataegus; at least four dispersal events are
      inferred to explain the present distribution of the genus.

PMID- 19405186
TI  - Opioid-induced hyperalgesia in a patient with dementia.

PMID- 19405187
TI  - The role of   MRI in the diagnosis of proximal femoral fractures in the  
      elderly.

PMID- 19405188
TI  - Molecular phylogenetics reveals extreme morphological homoplasy  in Brazilian
      worm lizards challenging current taxonomy.
AB  - Amphisbaenians are fossorial squamate reptiles distributed mainly in South
      America and Africa. Brazilian worm lizards belong to the family Amphisbaenidae,
      which has far more recognized species than any of the other five amphisbaenian
      families. Morphological datasets recovered Amphisbaenidae as paraphyletic, while
      previous molecular phylogenetic studies did not include enough taxa to solve the
      generic-level relationships within this family. We present a molecular
      phylogenetic hypothesis based on a sample of 58 amphisbaenians, including
      representatives of six of the seven South American genera. Our molecular data
      include sequences from two mitochondrial genes (16S, ND2; 1,184 characters) and
      three nuclear genes (RAG-1, C-MOS, BDNF; 1,898 characters). Our phylogenetic
      hypothesis is not fully resolved, although it does not support the monophyly of
      most genera except Leposternon. Morphological characters currently used to
      diagnose genera of South American amphisbaenians are homoplastic, and the
      taxonomy based on them is not appropriate. We revise the taxonomy of this group
      and sink several South American genera of Amphisbaenidae (Cercolophia, Bronia,
      Aulura, Anops and Leposternon) into Amphisbaena.

PMID- 19405189
TI  - Dementia in multiple system atrophy: does it exist?

PMID- 19405190
TI  - Phylogeny and biogeography of Alangiaceae (Cornales) inferred from DNA 
      sequences, morphology, and fossils.
AB  - Alangiaceae, in the basal Asterid clade Cornales, consists of only one genus,
      Alangium. The genus has approximately 24 species distributed mainly in tropical
      and subtropical regions of the Old World and is well represented in the Tertiary
      fossil record of the northern hemisphere. We conducted phylogenetic and
      biogeographic analyses for Alangium by integrating data from DNA sequences,
      morphology, and fossils to evaluate systematic and biogeographic hypotheses. The
      results largely agree with the traditional classification of four sections within
      the genus, and suggest sects. Conostigma and Rhytidandra are successive sister
      taxa to a clade containing sects. Marlea and Alangium. Our results also indicate
      that the widespread species A. chinense consists of at least two lineages
      meriting recognition as distinct species. Biogeographic analysis using DIVA and
      divergence time dating with the Bayesian method (MULTIDIVTIME) resolved the
      ancestor of Alangium as being in S.E. Asia in the Late Cretaceous. Several
      intercontinental migrations involving the margin of the Tethys seaway (TESW), the
      North Atlantic land bridge (NALB) or the Bering land bridge (BLB), and long
      distance dispersals are suggested. The results support TESW for plant migration
      of thermophilic (including evergreen) taxa in the early Tertiary.

PMID- 19405191
TI  - Intracranial pathology in elders with blunt head trauma.

PMID- 19405192
TI  - Treatment of multifocal motor neuropathy with immunoglobulin: does route of
      administration matter?

PMID- 19405194
TI  - The elder patient   with suspected acute coronary syndromes in the emergency  
      department.

PMID- 19405193
TI  - Plastid and nuclear DNA markers reveal intricate relationships at subfamilial 
      and tribal levels in the soapberry family (Sapindaceae).
AB  - The economically important soapberry family (Sapindaceae) comprises about 1900
      species mainly found in the tropical regions of the world, with only a few genera
      being restricted to temperate areas. The infrafamilial classification of the
      Sapindaceae and its relationships to the closely related Aceraceae and
      Hippocastanaceae - which have now been included in an expanded definition of
      Sapindaceae (i.e., subfamily Hippocastanoideae) - have been debated for decades.
      Here we present a phylogenetic analysis of Sapindaceae based on eight DNA
      sequence regions from the plastid and nuclear genomes and including 85 of the 141
      genera defined within the family. Our study comprises 997 new sequences of
      Sapindaceae from 152 specimens. Despite presenting 18.6% of missing data our
      complete data set produced a topology fully congruent with the one obtained from
      a subset without missing data, but including fewer markers. The use of additional
      information therefore led to a consistent result in the relative position of
      clades and allowed the definition of a new phylogenetic hypothesis. Our results
      confirm a high level of paraphyly and polyphyly at the subfamilial and tribal
      levels and even contest the monophyletic status of several genera. Our study
      confirms that the Chinese monotypic genus Xanthoceras is sister to the rest of
      the family, in which subfamily Hippocastanoideae is sister to a clade comprising
      subfamilies Dodonaeoideae and Sapindoideae. On the basis of the strong support
      demonstrated in Sapindoideae, Dodonaeoideae and Hippocastanoideae as well as in
      14 subclades, we propose and discuss informal groupings as basis for a new
      classification of Sapindaceae.

PMID- 19405195
TI  - Did glacials and/or interglacials promote allopatric incipient speciation in East
      Asian temperate plants? Phylogeographic and coalescent analyses on refugial 
      isolation and divergence in Dysosma versipellis.
AB  - To explore the evolutionary consequences of climate-induced fluctuations in
      presently fragmented temperate forest habitats in continental East Asia we
      investigated the phylogeography and demographic history of the temperate
      deciduous forest endemic Dysosma versipellis from disjunct montane sites in
      Central-Southeast China. Based on a survey of chloroplast (cp) DNA sequence
      variation, our analyses show that this perennial herb consists of morphologically
      indistinguishable western and central/eastern cpDNA lineages. Coalescent analyses
      under the 'isolation with migration' (IM) model support an ancient (Mid
      Pleistocene) divergence between these lineages, with the western lineage having
      persisted without significant population growth in a long-term refuge just east
      of the Tibetan (Qinghai-Xizang) Plateau. In contrast, for the central/eastern
      lineage, we found strong evidence for population expansion from a refuge located
      south of the middle and lower reaches of the Yangtze River, and likely coinciding
      with the last or penultimate interglacial, followed by considerable population
      isolation and divergence in situ over (at least) the latest glacial-interglacial
      cycle. In line with recent evidence from palaeomodeling of East Asian forest
      biomes, our results suggest that the same vicariance factor, i.e. climate-induced
      eco-geographic isolation through (a)biotic displacement of temperate-deciduous
      forested habitats, promoted the divergence of D. versipellis lineages and
      populations at different spatial-temporal scales and over glacial and
      interglacial periods. Thus, there is no evidence that populations of D.
      versipellis merged at lower elevations during the last glacial(s). As such, D.
      versipellis accords with the premise that Late Quaternary refugial isolation is
      likely to have enhanced allopatric (incipient) species formation of temperate
      plants in East Asia.

PMID- 19405196
TI  - Molecular evidence for the Southern Hemisphere origin and deep-sea 
      diversification of spiny lobsters (Crustacea: Decapoda: Palinuridae).
AB  - Spiny lobsters (family Palinuridae) are economically important marine animals
      that have been the subject of a considerable amount of research. However, the
      phylogeny of this group remains disputed. Morphological analyses have not been
      able to resolve the relationships of the various members of the group, and no
      agreement has yet been reached on its phylogeny as indicated by the different
      gene trees reported to date. In the present study, we attempt to reconstruct the
      phylogeny of Palinuridae and its allies using sequences from three nuclear
      protein-coding genes (phosphoenolpyruvate carboxykinase, sodium-potassium ATPase
      alpha-subunit and histone 3). The inferred topology receives strong nodal support
      for most of the branches. The family Palinuridae is found to be paraphyletic with
      the polyphyletic Synaxidae nested within it. Stridentes forms a monophyletic
      assemblage, indicating that the stridulating sound producing organ evolved only
      once in the spiny lobsters. By contrast, Silentes is paraphyletic, as
      Palinurellus is more closely related to Stridentes than to other Silentes genera.
      The three genera restricted to the southern high latitudes (Jasus, Projasus and
      Sagmariasus) constitute the basal lineages in the spiny lobsters, suggesting a
      Southern Hemisphere origin for the group. Subsequent diversification appears to
      have been driven by the closure of the Tethys Sea and the formation of the
      Antarctic circumpolar current, which isolated the northern and southern taxa.
      Contrary to an earlier hypothesis that postulated evolution from a deep-sea
      ancestral stock, the shallow-water genus Panulirus is the basal taxon in
      Stridentes, while the deep-sea genera Puerulus and Linuparus are found to be
      derived. This indicates that the spiny lobsters invaded deep-sea habitats from
      the shallower water rocky reefs and then radiated. Our results suggest that
      Synaxidae is not a valid family, and should be considered to be synonymous with
      Palinuridae. We also found that the previously proposed subgenera Sagmariasus and
      Nupalirus are genetically highly diverged, and both warrant a generic status.

PMID- 19405197
TI  - Bulbar and spinal muscular atrophy (Kennedy's disease): a review.
AB  - Bulbar and spinal muscular atrophy (BSMA) is an adult-onset, X-linked recessive
      trinucleotide, polyglutamine disorder, caused by expansion of a polymorphic CAG
      tandem-repeat in exon 1 of the androgen-receptor (AR) gene on chromosome Xq11-12.
      Pathogenetically, mutated AR accumulates in nuclei and cytoplasm of motor
      neurons, resulting in their degeneration and loss. Phenotypically, patients
      present with amyotrophic, proximal or distal weakness and wasting of the facial,
      bulbar and limb muscles, occasionally sensory disturbances, and endocrinologic
      disturbances, such as androgen resistance, gynecomastia, elevated testosterone or
      progesterone, and reduced fertility. There may be mild hyper-CK-emia, abnormal
      motor and sensory nerve conduction studies, and neuropathic and myopathic
      alterations on muscle biopsy. The golden standard for diagnosing BSMA is genetic
      analysis, demonstrating a CAG-repeat number >40. No causal therapy is available,
      but symptomatic therapy should be provided for tremor, endocrinologic
      abnormalities, sensory disturbances, or muscle cramps. The course is slowly
      progressive, the ability to walk lost only late in life, only few patients
      require ventilatory support, and life expectancy only slightly reduced.

PMID- 19405199
TI  - Comparative phylogeography of two endemic birds of the Tibetan plateau, the white
      rumped snow finch (Onychostruthus taczanowskii) and the Hume's ground tit
      (Pseudopodoces humilis).
AB  - Postglacial colonization has created the main phylogeographical structures in the
      endemic species of the Tibetan plateau; however, patterns of diversification are
      species idiosyncratic and indicative of variations in geographic divergence. Here
      we compare the phylogeographical structures of two endemic birds of the Tibetan
      plateau, the white-rumped snow finch (Onychostruthus taczanowskii) and the Hume's
      ground tit (Pseudopodoces humilis), both of which are commonly associated with
      alpine meadow habitats. Our results suggested that these two species experienced
      rapid population expansion at times estimated as 0.05-0.16 million years ago
      (Ma). These expansion periods were congruent with the retreat of the last
      extensive glacial period (0.5-0.175 Ma). Whereas O. taczanowskii populations were
      derived from a single more widely distributed refugium that existed along the
      east margin of the Tibetan plateau, P. humilis expanded from independent refugia
      that were located within both the northeast and southeast margin of the Tibetan
      plateau. While both birds experienced similar colonization events, their
      phylogeographical structures are quite contrasting. No trace of geographical
      divergence is found in O. taczanowskii, suggesting that considerable gene flow
      occurred after the postglacial colonization. In contrast, a geographic separation
      can be detected between two refugia populations of P. humilis, specifically the
      higher altitude platform and lower altitude edge regional groups. The gene flow
      between these two regions is restricted (M = 0.43). We estimate the divergence
      time as approximately 0.361 Ma, dating to the extensive glacial period. Potential
      explanations for the different phylogeographical structures of these two
      sympatric birds may include variance in dispersal ability, altitude specific and
      independent or semicontinuous refugia. While a combination of high flight ability
      and semicontinuous refugium may have promoted gene flow in O. taczanowskii
      populations, weak dispersal coupled with separated refugia may have sufficiently
      isolated populations such to facilitate genetic divergence in P. humilis.

PMID- 19405198
TI  - Optimizing referral of patients with neuromuscular disorders to allied health
      care.
AB  - BACKGROUND AND PURPOSE: To report the predictive validity of the perceived
      limitations in activities and need questionnaire (PLAN-Q), a screening instrument
      to support neurologists to select patients with neuromuscular disorders (NMD) for
      referral for a one-off consultation by occupational therapist (OT), physical
      therapist (PT) and speech therapist (ST). METHODS: In a cross-sectional
      validation study, 102 patients with various NMD participated. Patients received a
      one-off consultation by an expert OT, PT and ST and filled out the PLAN-Q.
      Therapists rated the appropriateness of the one-off consultations based on need,
      available treatment and patient's motivation. Receiver Operation Characteristic
      analysis and multivariate logistic regression analysis were used to obtain a PLAN
      Q based prediction model for the appropriateness of the one-off consultations.
      RESULTS: Probability for a one-off OT consultation increased from 64% to 78% (95%
      CI: 69-85%). Prior test probability for a one-off ST consultation increased from
      44% to 61% (95% CI: 48-73%). Prior test probability for one-off PT consultation
      could not be increased. CONCLUSION: Screening patients with NMD using the PLAN-Q
      may assist neurologists in selecting the appropriate patients for a one-off
      consultation by OT and ST. Unlike our expectations the screening did not guide
      referral for a one-off consultation by PT.

PMID- 19405200
TI  - Nuclear and mitochondrial diversification in two native California minnows: 
      insights into taxonomic identity and regional phylogeography.
AB  - Diversification of the California icthyofauna has been greatly influenced by a
      complex geomorphological history and past fluctuations in climate regimes. This
      complex history has resulted in areas of high endemism for a number of taxa. Here
      we present data on the two species in the genus Lavinia, the California roach
      (Lavinia symmetricus) and hitch (Lavinia exilicauda), that are widespread
      throughout the region. Individuals were sequenced at two mitochondrial DNA
      fragments and genotyped at eight microsatellite loci. Mitochondrial DNA indicated
      the presence to two highly divergent clades representing roach from the Gualala
      and Pit Rivers, which diverged from all other Lavinia approximately 3-6 MYA.
      Support was also foundfor roach from the Navarro River, Tomales Bay region, the
      Red Hills region, and the Russian River-Clear Lake basin. We found no evidence
      for any geographical groupings of mtDNA haplotypes for roach and hitch from the
      Monterey Bay region and the Sacramento-San Joaquin River drainages. Additionally
      roach and hitch from these two areas could not be readily distinguished by mtDNA
      data. Analysis of microsatellite DNA recovered all groupings found in the mtDNA
      analysis and was able to separate out roach, hitch, and all currently recognized
      subspecies of each species. These results indicate that hybridization may obscure
      the phylogenetic/phylogeographic informativeness of mtDNA in this group.
      Additionally, these results suggest that differentiation in this group occurs at
      the river basin level and that the described genetic entities constitute distinct
      units and should be conserved as such.

PMID- 19405201
TI  - Evolutionary inferences on the diversity of the genus Aotus (Platyrrhini,
      Cebidae)  from mitochondrial cytochrome c oxidase subunit II gene sequences.

PMID- 19405202
TI  - Comparison of the characteristics for in-hospital and out-of-hospital ischaemic
      strokes.
AB  - BACKGROUND AND PURPOSE: Patients who are being admitted to a hospital due to
      diseases other than stroke may develop a stroke (in-hospital stroke; IHS).
      METHODS: We enrolled 111 consecutive patients who developed IHS outside a
      neurology ward during a 5-year period at a single hospital. The frequency,
      characteristics, and outcomes for IHS patients were compared with patients who
      develop ischaemic stroke outside of the hospital (out-of-hospital stroke; OHS).
      RESULTS: Forty-six percent of IHS occurred in the department of cardiology or
      cardiovascular surgery and 60% were associated with surgery or procedures. In
      comparison with the OHS patient group, the IHS patient group showed an increased
      frequency of cardiac disease, leukocytosis, and anemia. Cardioembolism, stroke of
      other determined etiologies, and an incomplete evaluation were more common in the
      IHS group, whereas large artery atherosclerosis was more frequent in the OHS
      group. The IHS group had up to a 10-fold higher mortality than the OHS group,
      with sepsis being the most common cause of death in the IHS group. CONCLUSIONS:
      IHS has distinct etiologies and stroke mechanisms from OHS. The prevention and
      management of infection could decrease mortality in IHS patients.

PMID- 19405203
TI  - Population genetic structure and geographical differentiation of the Chinese
      catfish Hemibagrus macropterus (Siluriformes, Bagridae): evidence for altered
      drainage patterns.

PMID- 19405204
TI  - Cytomegalovirus ventriculoencephalitis presenting as a Wernicke's encephalopathy
      like syndrome.

PMID- 19405205
TI  - Botulinum toxin for trigeminal neuralgia.

PMID- 19405207
TI  - FL: Anesthesiologist fails to intubate reflux Pt: was death forty-two days later
      a triable issue?

PMID- 19405206
TI  - Comment on AAN-EFNS guidelines on trigeminal neuralgia management.

PMID- 19405208
TI  - Advances in oocyte cryopreservation--part II: rapid cooling using vitrification.
AB  - PURPOSE: The need for freezing oocytes has been established for females
      undergoing potential therapy that could damage their ovarian egg reserve, for
      ethical or religious reasons (not having excess embryos frozen) or for women
      nearing the age of lower fecundity but not married and not ready to use donor
      sperm. Applying cryopreservation techniques for oocytes used for embryos resulted
      in very poor pregnancy results. A rapid flash freezing technique has rekindled
      interest in oocyte freezing known as vitrification. METHODS: Certain
      modifications, especially minimizing the volume, have resulted in marked improved
      pregnancy rates with vitrified thawed oocytes. The lower volume allows decreased
      exposure to the toxic cryoprotection. Commercial interests have developed an
      effective device called cryotop but some concerns about microorganism
      contamination exist because it is an open system. Modifications have been made to
      make available the cryotip, a closed device which addresses the contamination
      issue. RESULTS: Frozen oocyte survival rates upon thawing fertilization rates and
      subsequent pregnancy rates after embryo transfer have been reported comparable to
      data with frozen thawed embryos. CONCLUSIONS: Because of the uncertainty of the
      programmable freezer used for the slow cool method and because there has been
      more commercial interest in the vitrification method, the "flash" freeze protocol
      seems to have an edge over the slow cool method for oocyte freezing.

PMID- 19405209
TI  - Three successful pregnancies following natural conception over an 8-year time
      span despite serum follicle stimulating hormone level greater than 15 mIU/ml.
AB  - PURPOSE: To demonstrate that the concept that a level of serum follicle
      stimulating hormone (FSH) of > 15 mIU/ml on day 3 of a younger woman's menstrual
      cycle suggests that the remaining eggs are of very poor quality consistent with a
      woman of very advanced reproductive age is a fallacy. METHODS: A woman with a
      serum FSH > 15 mIU/ml on day 3 was studied over an 8-year time period. RESULTS:
      Despite the absence of therapy with follicle maturing drugs, and at the latter
      part of the study the development of oligomenorrhea, the woman had three
      successful conceptions over eight years without ART techniques. Though two of her
      pregnancies were treated with progesterone starting in the luteal phase, her last
      pregnancy was without any treatment. CONCLUSIONS: The policy of certain
      physicians to advise couples that their eggs are extremely unlikely to develop
      into a normal pregnancy because of increased day 3 serum FSH and that they should
      immediately proceed to using donor oocytes (even if that is not their desire) is
      wrong. These women should be given an attempt to achieve a pregnancy with their
      own eggs. However, the treating physician should avoid the use of high-dosage
      follicle maturing drugs.

PMID- 19405210
TI  - Type I error robustness of ANOVA and ANOVA on ranks when the number of treatments
      is large.
AB  - Agricultural screening trials often involve a large number (t) of treatments in a
      complete block design with limited replication (b = 3 or 4 blocks). The null
      hypothesis of interest is that of no differences between treatments. For the
      commonly used analysis of variance (ANOVA) procedure, most texts do not discuss
      agreement between actual and nominal Type I error rates in the presence of
      nonnormality, in this small b, large t, situation. Similarly, for the Friedman
      and the increasingly popular "ANOVA on ranks" procedures, it is not easy to find
      results concerning null performance given b small and t large. In this article,
      we therefore present results, from two different bodies of theory, that provide
      useful insight concerning null performance of these ANOVA and rank procedures
      when t is large. The two types of theory are (i) the classical approach based on
      moment approximations to the permutation distribution, and (ii) central-limit
      theory-based asymptotics in the nonstandard t--> infinity situation. Both
      approaches demonstrate the validity of standard ANOVA and of ANOVA on within
      block ranks, under nonnormality when t is large. Choice of the procedure to be
      used on a given data set should therefore be based on consideration of power
      properties. In general, ANOVA on ranks will be superior to standard ANOVA for
      data with frequent extreme values.

PMID- 19405211
TI  - Outbreak news. Swine influenza.

PMID- 19405212
TI  - Psychological health.

PMID- 19405213
TI  - Statistical implications of the choice between a dichotomous or continuous trait
      in studies of interobserver agreement.
AB  - A frequently occurring question in the planning of studies is whether to measure
      the trait of interest on a continuous or dichotomous scale. An issue potentially
      relevant to this question centers around the resulting reliability of the
      measure. Assuming the continuous trait has a normal distribution, we quantify the
      effect of this decision on the overall number of subjects required to test
      whether a population reliability coefficient equals a specified criterion value.
      Two distinct cases are explored: the choice between a continuous response and a
      truly dichotomous response, and the case in which an inherently continuous
      response is dichotomized. In both cases, and particularly in the second, the loss
      of power associated with measuring the trait on a dichotomous scale is shown to
      be always severe and frequently prohibitive.

PMID- 19405214
TI  - The collection of William G. Myers M.D., Ph.D., the godfather of the cyclotron.

PMID- 19405215
TI  - Detecting change in the composition of multispecies community.
AB  - This paper describes an approach to extracting a trend from a time series of the
      composition of a multispecies community. The approach is based on a modification
      of a method for trend extraction from ordinary multiple time series. Two
      applications to a Northwest Atlantic ecosystem are described.

PMID- 19405217
TI  - Virulence mechanisms of Moraxella in the pathogenesis of infection.
AB  - PURPOSE OF REVIEW: Moraxella catarrhalis is an emerging human-specific pathogen
      responsible for upper and lower respiratory tract infections. Understanding the
      events in the complex pathogenesis and underlying mechanisms during M.
      catarrhalis infection is a key to the development of novel therapeutics and
      vaccines. RECENT FINDINGS: Several novel findings have been reported on Moraxella
      pathogenesis and, in parts, explain how the species stands as a commensal in
      preschool children and survives in the host. Molecular structures for different
      adhesins in addition to target ligands with respect to signalling and invasion
      have been defined. Evasion of the complement system allows Moraxella to survive
      in the mucosa and by neutralizing [alpha]1-antichymotrypsin the protease activity
      is increased, resulting in tissue destruction and thus promotion of bacterial
      attachment. Moraxella-dependent cell activation via immunoglobulin D in addition
      to toll-like receptors and specific epithelial cell inhibition by cross-linking
      of carcinoembryonic antigen-related cell adhesion molecule-1 in the early innate
      immune response and, finally, the ability of M. catarrhalis to form biofilms are
      other specific research areas of interest. SUMMARY: Recent advances have allowed
      a more detailed picture of the processes involved in bacteria-host cell
      interactions, the cause of inflammatory processes and specific host defense
      responses against the intriguing species Moraxella.

PMID- 19405216
TI  - Management of paediatric HIV-1 resistance.
AB  - PURPOSE OF REVIEW: Children have higher rates of virological failure than adults,
      often associated with more extensive resistance and limited second-line options.
      In order to maintain clinical benefits of highly active antiretroviral therapy
      (HAART) into adulthood, particularly for children starting at a young age,
      strategies are needed to limit the emergence of resistance and to offer highly
      effective subsequent lines of therapy. Similarly, well resourced settings face
      challenges regarding extensive resistance accumulated over the past decade or
      more, particularly resulting from suboptimal therapies. RECENT FINDINGS: Rates of
      resistance at failure of nonnucleoside reverse-transcriptase inhibitor based
      HAART are higher in developing countries than in well resourced settings. In the
      latter, second-generation protease inhibitors tipranavir and darunavir are
      promising, with tipranavir now licensed for those above 2 years and darunavir
      showing good trial results in children above 6 years. However, combination with
      new classes such as integrase inhibitors (currently in phase I trials) and CCR5
      antagonists (no paediatric data yet) will probably be necessary to gain maximal
      long-term benefits. SUMMARY: Common goals in paediatric HIV for both resource
      rich and resource-limited settings are to limit vertical transmission, minimize
      emergence of resistant viruses in both mother and child where prevention of
      mother-to-child transmission fails, and limit resistance in children starting
      HAART. Optimal sequencing of regimens in the absence of resistance testing is a
      priority research area. Paediatric studies using newer classes of agents are of
      paramount importance, as well as expanding access to existing antiretrovirals.

PMID- 19405218
TI  - Space, authority and the female emigrant afloat.
AB  - In the latter half of the nineteenth century, all emigrants travelling out to the
      Australian colonies experienced a range of measures designed for their
      protection. As well as physical protection, the future roles of single emigrant
      women, as paid domestic labour or, ultimately, as unpaid wives and mothers,
      required that the care accorded to them also took on social and moral concerns.
      This paper discusses the shipboard structures, particularly spatial arrangements,
      that were designed both to protect emigrant women in transit to the colonies and
      to protect the colonial investment.

PMID- 19405219
TI  - Marriage as bondage: the anomaly of the citizen wife.
AB  - The meaning of marriage for women was a hotly disputed issue in Australia during
      the first half of the twentieth century and beyond. Conscious of their status as
      citizens, interwar feminists became preoccupied with the anomalous condition of
      wives in a modern democracy. The provision of personal service in exchange for
      keep, the condition of wives was defined as an anachronism, a political relic, a
      form of feudal bondage. Feminists campaigned for the economic independence of
      married women, demanding legislation that would give wives legal ownership of
      household savings as well as a legal entitlement to a share in their husbands'
      wages.

PMID- 19405220
TI  - Changi: a place of personal pilgrimages and collective histories.
AB  - This article investigates the meaning that the Changi historical site has had for
      its visitors. The study traces how the landmarks and relics of the former
      prisoner-of-war camp at Changi in Singapore have been re-created and, in some
      cases, relocated for the public since the end of World War II. Changi's meaning
      as a place is derived not only from the significance that it has for the ex
      prisoners of war and their relatives, who frequently revisit the site: many
      visitors for whom Changi represents a major historical event in their own
      national history also attach considerable importance to the site.

PMID- 19405221
TI  - Women in the discourse of Balzac's Horace Bianchon.

PMID- 19405222
TI  - [Gautier's Tahoser and Flaubert's Salammbo: the Oriental woman and the voyage
      beyond history].

PMID- 19405223
TI  - "Blanche et Noir": Louise Faure-Favier and the liberated woman.

PMID- 19405224
TI  - Molecular imaging of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) are a renewable source of differentiated cell
      types that may be employed in various tissue regeneration strategies. However,
      clinical implementation of cell transplantation therapy is hindered by legitimate
      concerns regarding the in vivo teratoma formation of undifferentiated hESCs and
      host immune reactions to allogenic cells. Investigating in vivo hESC behaviour
      and the ultimate feasibility of cell transplantation therapy necessitates the
      development of novel molecular imaging techniques to longitudinally monitor hESC
      localization, proliferation, and viability in living subjects. An innovative
      approach to harness the respective strengths of various imaging platforms is the
      creation and use of a fusion reporter construct composed of red fluorescent
      protein (RFP), firefly luciferase (fluc), and herpes simplex virus thymidine
      kinase (HSV-tk). The imaging modalities made available by use of this construct,
      including optical fluorescence, bioluminescence, and positron emission tomography
      (PET), mat be adapted to investigate a variety of physiological phenomena,
      including the spatio-temporal kinetics of hESC engraftment and proliferation in
      living subjects. This chapter describes the applications of reporter gene imaging
      to accelerate basic science research and clinical studies involving hESCs through
      (1) isolation of a homogenous hESC population, (2) noninvasive, longitudinal
      tracking of the location and proliferation of hESCs administered to a living
      subject, and (3) ablation of the hESC graft in the event of cellular misbehavior.

PMID- 19405225
TI  - A distinctive cinema culture.

PMID- 19405226
TI  - Gendered configurations of colonial and metropolitan space in "Pepe le Moko".

PMID- 19405227
TI  - Policy reform and the politics of housing in the British Conservative Party 1924
      1929.

PMID- 19405228
TI  - Abstracts of the 5th International Meeting for Affective, Behavioural and
      Cognitive Disorders in the Elderly.February 26-28, 2009. Verona, Italy.

PMID- 19405229
TI  - Model workers or hardened Nazis? The Australian debate about admitting German
      migrants, 1950-1952.

PMID- 19405231
TI  - Drawing the line: sex education and homosexuality in South Australia, 1985.

PMID- 19405233
TI  - Case of the month. Heck's disease (focal epithelial hyperplasia).

PMID- 19405234
TI  - Benign mucous membrane pemphigoid concurrent with primary sclerosing cholangitis.

PMID- 19405236
TI  - Technology in the dental office--is your practice up to speed?

PMID- 19405235
TI  - Designing a dental office.

PMID- 19405237
TI  - Removing the shield that minimizes new patient flow.

PMID- 19405238
TI  - Dental lab CE and point of origin law now in effect.

PMID- 19405239
TI  - Diversifying the operation: Southern Baptist missions in China at the turn of the
      century 1890-1910.

PMID- 19405240
TI  - [Psychological history in France, 1968-97: a 14 November 1998 conference in
      Ghent].

PMID- 19405241
TI  - [The beginnings of the Pflege Journal and its publishers, especially Silvia
      Kappeli, who took measure and became a standard setter].

PMID- 19405242
TI  - [Basic principles of diver medical certification].

PMID- 19405243
TI  - [Extreme mountain climbing with type 1 diabetes].

PMID- 19405244
TI  - Improving vaccination cold chain.

PMID- 19405245
TI  - Symptom experience of family caregivers of patients with cancer.
AB  - OBJECTIVES: To review the literature on depression, anxiety,sleep disturbance,
      fatigue, and pain in family caregivers of patients with cancer in the context of
      the Symptom Management Model (SMM)developed at the University of California, San
      Francisco (UCSF). DATA SOURCES: Published research studies and systematic reviews
      from 1990-2007. DATA SYNTHESIS: Studies of depressive symptoms in caregivers of
      patients with cancer were the most numerous. A limited number of studies examined
      anxiety, fatigue, sleep disturbance, and pain. Most studies focused on the
      symptom experience dimension of the UCSF SMM. CONCLUSIONS: Based on the small
      sample sizes, cross-sectional nature of the studies, and lack of comparison
      groups, little is known about the prevalence and effects of symptoms in
      caregivers of patients with cancer. IMPLICATIONS FOR NURSING: Additional research
      is needed to determine the prevalence, severity, and effects of symptoms on
      caregivers. Better descriptive, correlational studies will lead to the
      development of interventions to improve symptom management for this group of
      caregivers.

PMID- 19405246
TI  - What happened at the College of Physicians of Philadelphia?

PMID- 19405247
TI  - E-Resources at the Osler Library: special collections databases, the Canadian
      Health Obituaries Index File, and the Bibliography of Canadian Health Sciences
      Periodicals.

PMID- 19405248
TI  - National Museum of Health and Medicine digitization project.

PMID- 19405249
TI  - Apgar Papers at NLM.

PMID- 19405251
TI  - Bringing it to the masses: introducing Med I students to medical history through
      the Ohio State University Medical Heritage Center.

PMID- 19405250
TI  - Art, literature, and medicine.

PMID- 19405252
TI  - Netter exhibit in New Jersey.

PMID- 19405253
TI  - Genetics of Crohn's disease.

PMID- 19405254
TI  - Genetic testing for cancer prevention: are we ready for it?

PMID- 19405255
TI  - Effect of bending exercise on gastroesophageal reflux in symptomatic patients.
AB  - BACKGROUND: Recumbency and bending are thought to provoke symptoms of reflux in
      patients with gastroesophageal reflux disease (GERD). The effect of exercise
      which involved bending and abdominal contractions was evaluated in symptomatic
      patients of GERD using continuous 24-hour ambulatory esophageal pH test. METHODS:
      Twenty-five patients with GERD, confirmed by abnormal 24-hour esophageal pH
      study, performed exercise for 30 minutes consisting of 5 sessions of 6 minutes
      each. The exercise involved toe touching from supine, sitting and standing
      position of 2 minutes' duration each. Each 2 minutes' period included 8
      repetitions of the same exercise of 15 seconds' duration. 24-hour esophageal
      pHmetry was done on day 1 without exercise and on day 2 with 30-minute exercise.
      Reflux time percent (RT%) pH <4 was compared between days 1 and 2 and 30 minutes
      before and during exercise. RESULTS: Fourteen patients were upright refluxers and
      11 patients were combined refluxers, which included 4 patients with supine reflux
      and 7 patients who refluxed both in supine and upright positions. The median
      (range) 24-hour RT% on day 1 and day 2 was 7 (5-40) and 7 (4-46), respectively
      (p=0.15). RT% during 30 minutes exercise compared with 30 minutes before exercise
      was 6.6 (0-60) and 0.0 (0.0-80) (p=0.02), respectively. In combined and upright
      refluxers, RT% during and before exercise was 13 (0-53) and 0.0 (0.0-42)
      (p=0.008), respectively and 0.0 (0-60) and 0.0 (0-80), (p=0.71), respectively.
      RT% between upright and combined refluxers during exercise was 0.0 (0-60) and 13
      (0-53), respectively (p=0.004). The mean (SD) LES pressure in mmHg in combined
      and upright refluxers was 7 (2.9) and 19.6 (6.8), respectively (p=0.008).
      Esophagitis in combined and upright refluxers was seen in 8 patients (72.7%) and
      2 patients (14.3%), respectively. Two patients (8%) developed symptoms during
      exercise. CONCLUSION: Exercise which involves bending precipitates reflux in
      patients with moderate-to-severe GERD.

PMID- 19405256
TI  - Cyclosporine in the treatment of severe steroid refractory ulcerative colitis: a
      retrospective analysis of 24 cases.
AB  - BACKGROUND: Cyclosporine A (CsA) has been found to be the first successful
      therapy used in the recovery of patients with steroid-refractory ulcerative
      colitis (UC). However, the long-term benefits of cyclosporine remain
      questionable. We report our results on the use of CsA in patients with severe
      steroid-refractory UC. METHODS: The records of all patients with steroid
      refractory UC treated with CsA from January 2003 to December 2007 were reviewed.
      Demographics, clinical characteristics of the disease, responsiveness to CsA,
      complications arising from the treatment and the need for surgery were recorded
      for all patients. RESULTS: Of 146 admissions of severe UC, 24 patients who were
      steroid refractory (mean age 41.7 years; 11 men) received intravenous
      cyclosporine (4 mg/kg/day) for mean of 6.63 days (range 1-7), followed by oral
      CsA for a period of 3 months. All patients had failed to respond to intravenous
      hydrocortisone given for 7 days. Four patients required a colectomy immediately,
      three of whom failed to respond to CsA, and one had convulsions following drug
      administration. Nineteen of the 24 patients (79%), in whom a colectomy was
      avoided during the early stages of their treatment, were followed up for a mean
      of approximately 38 months (range 12-62 months). Three patients required surgery
      on follow up; one was operated at day 94, another in the second year and one in
      the third year. Overall, 16 of 24 patients (67%) remained colectomy-free. The
      main side-effects observed included infections, tremors, paresthesias, headache,
      hypertension, hypertrichosis and peripheral neuropathy. Three of seven patients
      who had to undergo surgery died within 2 weeks. CONCLUSIONS: Our study shows that
      surgery can be avoided in two-thirds of patients with steroid refractive severe
      UC. However, the drug toxicity and mortality are significant.

PMID- 19405257
TI  - Acute mesenteric ischemia: causes and mortality rates over sixteen years in
      southern Iran.
AB  - Acute mesenteric ischemia (AMI) is a catastrophic disorder of the
      gastrointestinal tract with high mortality. Few data on the characteristics of
      this disease in Iran are available. Patient records of public and private
      hospitals in Shiraz, southern Iran, with impression of acute abdomen, bowel
      gangrene or abdominal pain, and patients with risk factors for this disease, who
      were admitted between March 1989 and March 2005, were reviewed. Among the 10,000
      patient records studied, 105 patients (mean age 57 years) with AMI were
      identified. The mortality rate was 50.4%. The most common symptom was abdominal
      pain (98.1%). Heart diseases were seen in 44.7% of cases. The mortality rate was
      lower in patients undergoing mesenteric angiography (p=0.014). In those patients
      in whom the site of lesion was identified, venous thrombosis was the most common
      type (41.9%). AMI is a common cause of acute abdomen especially in elderly
      patients, with venous thrombosis being the most common type.

PMID- 19405258
TI  - Ramadan fasting and inflammatory bowel disease.
AB  - Ramadan fasting may induce changes in gastrointestinal physiology. The effect of
      this fasting on inflammatory bowel disease (IBD) is not known. We conducted a
      cohort study in the month of Ramadan in 2006 to assess the effect of Ramadan
      fasting on IBD. Sixty patients with IBD, who were in remission and undertook
      fasting according to their own free will underwent assessment of quality-of-life
      (QoL) parameters, psychological state and the severity of symptoms before and
      after Ramadan. There was no correlation between the number of fasting days and
      the severity of the disease, QoL and psychological state of the patients. QoL did
      not change after Ramadan. Younger patients with ulcerative colitis (UC) fasted
      for a greater number of days (p=0.01) compared to older patients. The mean score
      of anxiety, using a modified version of the Hospital Anxiety and Depression Scale
      was 12.7 (6.0) before Ramadan in women with UC, and decreased to 9.8 (4.4)
      afterfasting (p=0.026). Men with UC had a mean score of colitis activity index of
      3.5 before Ramadan, which decreased to 1.7 after fasting (p=0.008). It appears
      that Ramadan fasting does not impose serious risks on patients with IBD.

PMID- 19405260
TI  - Dissolution of pharmacobezoar using carbonated beverage.
AB  - Bezoars are concretion of undigested material found in the upper alimentary
      tract, particularly the stomach. Physiologic disturbances such as
      gastrointestinal dysmotility or anatomical derangements have been described as
      contributory in most cases of pharmacobezoars. Gastric phamacobezoars can be
      treated with endoscopic fragmentation or surgery. Gastric lavage with carbonated
      beverage has been successfully used to treat gastric phytobezoars. We report a 67
      year-old man with pharmacobezoar successfully treated by infusion and intrabezoar
      injection of carbonated beverage. Subsequent endoscopy revealed an underlying
      adenocarcinoma in the stomach.

PMID- 19405259
TI  - An Indian family of multiple endocrine neoplasia type 1 (MEN1): molecular
      diagnosis, treatment and follow up.
AB  - BACKGROUND/OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal,
      dominant syndrome, characterized mainly by the combination of tumors involving
      the parathyroid, pancreatic and pituitary glands. Genetic sequencing leading to
      early treatment of family members has not yet been reported in Indian patients.
      METHODS: We performed molecular analysis of the MEN1 gene to identify mutations
      in an Indian family with MEN1 syndrome. The proband was identified with multiple
      peptic ulcers because of multifocal recurrent gastrinomas, as well as parathyroid
      and pituitary adenomas. All the 10 exons of the MEN1 gene were amplified using
      the polymerase chain reaction (PCR). The MEN1 gene was then screened by direct
      DNA sequencing. RESULTS: The proband is asymptomatic 3 years after total
      pancreatectomy and removal of parathyroid adenomas. DNA sequencing revealed the
      presence of a heterozygous Y227X mutation in exon 4 of the MEN1 gene in the
      proband. Four of the seven mutant-carrying family members are at present
      asymptomatic. Following screening, one asymptomatic child has been identified
      with and treated for insulinoma and parathyroid adenoma. CONCLUSION: Detection of
      the MEN1 gene mutation enables selection of family members for screening and long
      term follow up.

PMID- 19405261
TI  - IGF-I as a marker of disease activity and nutritional status in patients with
      inflammatory bowel disease.

PMID- 19405262
TI  - Helicobacter pylori positivity in esophageal and esophagogastric junction
      adenocarcinoma.

PMID- 19405263
TI  - Cholestatic hepatitis due to azathioprine and tacrolimus in a adult renal
      allograft recipient.

PMID- 19405264
TI  - Pajamas with a hole: a holistic solution to an embarrassing problem.

PMID- 19405265
TI  - Acute pancreatitis in viral infections with possible progression to chronic
      pancreatitis.

PMID- 19405266
TI  - Hepatocellular carcinoma infiltrating the duodenum presenting as hematemesis.

PMID- 19405267
TI  - Hepatocellular carcinoma with intravascular and right atrial extension.

PMID- 19405268
TI  - Detection of retroperitoneal fistula of the colon by CT colonography.

PMID- 19405269
TI  - [Low back pain, frequent symptoms with multiple facets].

PMID- 19405270
TI  - [Conservative treatment of chronic low back pain: what is new in 2008?].
AB  - An overview of the recent literature on chronic low back pain is presented from a
      general practitioner's perspective. Several drugs are available however the
      magnitude of their effect is low and they should be tailored to patient's
      preference. The cost-benefit ratio of strong opioid is controversial. Different
      types of exercises have favourable effect on function and quality of life. Graded
      activity, taking into account kinesio-phobia, may be more important than any
      specific type of exercise. Spinal infiltration should only be used in much
      selected patients. In case of unfavourable evolution, multidisciplinary
      approaches should be the next step. Caring for low back pain patients is a
      difficult exercise. There is no universal recipe. The emphasis should be put on
      tailoring treatment approaches to patient perspective.

PMID- 19405271
TI  - [Imaging in inflammatory spine diseases].
AB  - There is a mean delay of 5 to 8 years between the onset of symptoms and the
      diagnosis of ankylosing spondylitis. This is due to the fact that radiographic
      sacroiliitis is delayed. The purpose of an earlier diagnosis is emphasized by the
      need for better management, the new diagnostic method including magnetic
      resonance imaging and by the efficacy of anti-TNF therapy. The current criteria
      are classification but not diagnostic criteria. Their sensitivity is insufficient
      for an early diagnosis of ankylosing spondylitis. MRI criteria allow to
      differentiate inflammatory signs from degenerative signs in patients sent for
      aspecific low back pain. The aims of this article are to illustrate the different
      stages of the disease from early inflammatory involvement to ankylosis and to
      discuss the role of imaging in the management of affected patients.

PMID- 19405272
TI  - [Inflammatory back pain].
AB  - Inflammatory back pain is more than just inflammatory pain, but a set of symptoms
      which presence must evoke a diagnosis of ankylosing spondylitis. However, it is
      insufficient by itself for a diagnosis which can only be reach as part of a
      diagnostic strategy searching for other clinical, biological or radiological
      abnormalities in order to obtain adequate diagnostic probability, while
      acknowledging the limitations of all these examinations.

PMID- 19405273
TI  - [Radiculopathy due to lumbar disc herniation].
AB  - The knowledge on radiculopathy due to lumbar disc herniation has considerably
      improved over the last years. The physiopathology has been better characterised,
      new drugs are under investigation and thanks to high quality studies, and the
      role of surgery is now better defined. This review focused on practical
      principles for the general practitioner.

PMID- 19405274
TI  - [Lumbar spinal stenosis: scientific evidence of surgical treatment].
AB  - In 2000, Nachemson and coll. published a book about modern treatment of spine
      related pathologies. They concluded that evidence regarding efficiency of
      surgical and non surgical treatments of lumbar spinal stenosis was poor. Despite
      this and the fact that the precise mechanism of pain is still unknown, surgical
      treatment of spinal stenosis, mainly consisting in a laminectomy, has made it
      through the years. More recently, higher quality scientific publications have
      brought significant evidence that surgery yields better short and long term
      functional results, than non surgical conservative treatment. This advantage
      might also compensate for possible internistic complications in a usually older
      and fragile population.

PMID- 19405275
TI  - [Vertebro-plasty: a rheumatologist's point of view].
AB  - Percutaneous vertebro-plasty is an efficient treatment of the symptomatic
      vertebral compression fracture refractory to optimal medical therapy. The
      procedure is used for neoplastic lesions, aggressive angioma, but also
      osteoporotic compression fractures. In order to adequately advice our patients,
      it is essential to know its indications and possible complications. However, to
      practice a vertebro-plasty for an osteoporotic compression fracture without any
      long term management of the osteoporotic disease is useless. Unfortunately, it
      still happens too often and it is essential that orthopedic surgeons, general
      practitioner, radiologist, rheumatologist, and any practitioners work together to
      guarantee the optimal management of our patients.

PMID- 19405276
TI  - [Lina Stern, Genovese academician persecuted in the Soviet Union].

PMID- 19405277
TI  - [Hospitals in Neuchatel: a revolution from the Bottom to the Top ].

PMID- 19405278
TI  - [Medical ethics in outbreaks of human influenza].

PMID- 19405279
TI  - [What has become of the vapors of yester year].

PMID- 19405280
TI  - [Place of stem cells in cardiovascular therapy].

PMID- 19405282
TI  - [Laboratories and stress of mass media].

PMID- 19405281
TI  - [Influenza virus, human: two avenues for the new treatment].

PMID- 19405283
TI  - Insurance burden may be handed to nurses.

PMID- 19405284
TI  - Shedding pounds.

PMID- 19405285
TI  - We must not forget acute pain when improving pain services.

PMID- 19405286
TI  - Does applying pressure reduce pain in intramuscular injections?

PMID- 19405288
TI  - How effective are psychological therapies and antidepressants for irritable bowel
      syndrome?

PMID- 19405287
TI  - Palliative care 1: principles of palliative care nursing and end-of-life care.
AB  - The first in this three-part series examines the diversity and challenges
      inherent in nurses' contribution to palliative care. The art and the science of
      caring for those who are dying and their families has long been recognised as an
      immensely demanding and rewarding part of health and social care. For nurses, it
      is central to the values and principles that underpin clinical practice.

PMID- 19405290
TI  - An overview of acute exacerbations of COPD: assessing and preventing acute
      exacerbations of COPD.
AB  - COPD is a chronic respiratory disorder that is a major cause of morbidity for
      patients and carers, and is predicted to be the third leading cause of death
      worldwide by 2020 (Murray and Lopez, 1997). It is characterised by chronic
      airflow limitation, airway inflammation, structural changes to the airways and
      parenchyma and some systemic effects (Global Initiative for Chronic Obstructive
      Lung Disease (GOLD), 2008). It is primarily caused by smoking, although other
      causes such as occupational factors have been identified (NICE, 2004). This
      article aims to provide an overview of some important aspects of acute
      exacerbations of COPD that need to be considered by all healthcare professionals.

PMID- 19405289
TI  - We must not miss having our say on how local services are run.

PMID- 19405291
TI  - The nurse's role in managing patients with bronchiectasis: an overview of
      treatment and management of patients with bronchiectasis.
AB  - In a previous article on bronchiectasis, Alan Peres defined bronchiectasis, its
      pathophysiology and clinical manifestations, and how nurses may assess patients
      presenting with it (Peres, 2008). This article provides an overview of treatment
      and the role of the nurse in providing and managing the care of patients with
      this condition.

PMID- 19405292
TI  - Respiratory inhaled therapy 2: choosing an inhaler.
AB  - The second article in a two-part series takes a detailed look at what issues
      healthcare professionals should consider when selecting an inhaler for a patient.
      It looks at the differences between the different types and explains how they
      should be used. Part one looked at the use of pressurised metered dose inhalers
      (Heslop, 2008).

PMID- 19405293
TI  - On why there are so few BME nurses in senior NHS posts.

PMID- 19405294
TI  - The NHS is a resource to be protected not plundered.

PMID- 19405298
TI  - [French emergency medicine, a concept recognized by all].

PMID- 19405299
TI  - [A day with the triage nurse in the emergency service admission].

PMID- 19405300
TI  - [Specific and complementary nursing competences in the management of psychiatric
      emergencies].

PMID- 19405301
TI  - [Caring for the person during terminal care in the emergency room].

PMID- 19405302
TI  - [When the exercise of nursing care is in a context of aggression].

PMID- 19405303
TI  - [To be better informed on how to manage violent situations].

PMID- 19405304
TI  - [Being a new young nurse with a diploma. Interview by Jerome Jean].

PMID- 19405305
TI  - [The nursing care plan guide].

PMID- 19405306
TI  - [Preventing anxiety and pain in children in pediatric emergencies].

PMID- 19405307
TI  - [Screening and care of foot lesions in hemodialysis].

PMID- 19405308
TI  - [Education in targeted care planning].

PMID- 19405309
TI  - [Medication administration errors immediately reported by the nursing personnel].

PMID- 19405310
TI  - [Admission of low vision or blind persons to a health institution].

PMID- 19405312
TI  - [Omega 3 fatty acids].

PMID- 19405311
TI  - [Albert Calmette (1863-1933)].

PMID- 19405313
TI  - Patient advocacy in an era of financial constraints.

PMID- 19405314
TI  - The imperative for disease modifying treatments in Alzheimer's disease.

PMID- 19405315
TI  - Orthopaedic admissions due to sports and recreation injuries.
AB  - The health benefits of exercise may be attenuated by sports and recreation
      related injury (SRI). Though the majority of SRI are mild and self-limiting, a
      significant number are serious and require orthopaedic intervention. The aims of
      this study were to assess the burden of these serious injuries on the orthopaedic
      inpatient service, and to investigate potential target areas for injury
      prevention. All 1,590 SRI seen in the ED over a 3-month period were analysed
      using the Patient Information Management System to determine which patients
      received inpatient orthopaedic care. The medical records of those 63 patients who
      required inpatient care under orthopaedics were reviewed and data collected on
      demographic features, history, operative procedure and theatre resources, and
      length of hospital stay. Data were analyzed using SPSS. SRI accounted for 12.3%
      of all ED presentations. The principal activities resulting in injury requiring
      orthopaedic care were soccer, hurling and informal play e.g. trampoline. Falls
      made up 37% of the overall mechanism of injury but 68% of the injuries severe
      enough to require operative management. Most operative procedures were performed
      as part of a routine day trauma list but 20% were performed out of hours. This
      group of injuries places a significant burden on a busy trauma service. Injury
      prevention measures such as public education regarding falls in sport may have a
      role in reducing this burden.

PMID- 19405316
TI  - Benign prostatic hyperplasia presenting with renal failure--what is the role for
      transurethral resection of the prostate (TURP)?
AB  - The aim of the study was to determine the role of transurethralresection of
      prostate (TURP) in normalising renal function in men presenting with obstructive
      renal failure secondary to benign prostatic hyperplasia. We reviewed the cases of
      14 men who presented in the last 5 years with renal impairment associated with
      symptoms of bladder outflow obstruction and radiological evidence of obstructive
      uropathy. The mean serum creatinine at presentation was 632 ng/mL (range 1299 -
      225). The mean age at presentation was 68.2 years (range 50 - 83 years). Duration
      of symptoms prior to presentation ranged between 1 - 118 months (mean 21.5
      months). Following catheter insertion, all patients underwent TURP. Six of the 14
      patients required dialysis prior to surgery. Histology of the resected prostate
      confirmed benign prostatic hypertrophy and/or hyperplasia in all cases. Patients
      with carcinoma of the prostate were excluded from the study. Following TURP, 2 of
      the 14 men (14%) failed to void spontaneously following removal of catheter - one
      patient performs clean self intermittent catheterization (CSIC), the other man
      has an in-dwelling catheter in situ. One patient died 7 months following TURP due
      to a myocardial infarction. However, 8 patients, (57%) remained dialysis
      dependent following TURP. Two of these patients have since undergone successful
      renal transplantation. Of the remaining 6 patients, only 3 have normal renal
      function with the other 3 experiencing moderately elevated serum creatinine
      (range 236 - 344 ng/mL). In patients presenting with renal failure due to bladder
      outflow obstruction, TURP restores normal voiding pattern in many cases. However
      renal failure due to bladder outflow obstruction tends to be more refractory and
      only 3 of 14 patients experienced return to normal renal function post treatment.

PMID- 19405317
TI  - Vaccination--knowledge and attitudes of school children.
AB  - Low vaccine up-take in Ireland resulted in the measles epidemic of 2000-2001, and
      more recent outbreaks of mumps in many schools and colleges. Forty-five schools
      were selected from a list of secondary schools in Ireland using a table of random
      numbers, and teachers were requested to distribute self-administered
      questionnaires to their 4th year students. The questionnaires were analysed using
      Epi-Info and chi-square test. 86% (n=675) of students considered themselves
      inadequately informed about vaccines and vaccine-preventable diseases. 67.9%
      (n=532) wanted the topic added to the science syllabus. 88.3% (n=692) agreed that
      they would vaccinate their own children against all childhood diseases. It is
      recommended that the topic of vaccination be covered more completely by the
      Junior Certificate Science syllabus. It is concluded that the vaccination up-take
      rates in the Ireland should rise with the next generation.

PMID- 19405318
TI  - Severe bone demineralisation is associated with higher mortality in children with
      cystic fibrosis.
AB  - Decreased bone mineral density (BMD) is an emerging problem for clinicians who
      care for children with Cystic fibrosis (CF). The aim of this study was to
      determine prevalence and assess risk factors for reduced BMD in our adolescent
      population with CF. All bone densitometry scans (n=99) performed on children
      (n=79) with a mean age 13.6 (10-19.2) years over a 7 year period (2000-2007) were
      reviewed. Patient records were reviewed for correlating clinical data. Low BMD is
      frequently present in adults and children with variable reports (36-66%). In our
      study, BMD expressed as z score of L2-L4 spine was reduced in a total of 50%
      children with a preponderance of males. Bone demineralization was strongly
      associated with increasing age (p=0.03), diminished lung function (p=0.027),
      reduced body mass index (p=0.001) and treatment with oral corticosteroids
      (p=0.02).

PMID- 19405319
TI  - Knowledge of the indications for endoscopic ultrasound (EUS) among
      gastroenterologists and non-gastroenterologists.
AB  - The level of awareness among Irish doctors of the appropriate indications for
      endoscopic ultrasound (EUS) is unknown. This study assessed knowledge of EUS
      indications among consultants and trainees in 3 Irish teaching hospitals. A
      questionnaire was designed to test knowledge of EUS indications in 4 organ
      systems: oesophagus, gastroduodenum, hepatopancreatobiliary system and
      colorectum. The questionnaire was distributed to consultants and trainees (both
      gastroenterology and non-gastroenterology) in 3 major Irish teaching hospitals.
      The survey was distributed to 86 doctors, all of whom replied: 18 consultants (11
      gastroenterologists,) 40 registrars (28 gastroenterology) and 26 SHOs/interns.
      Knowledge of appropriate EUS indications was best among consultant
      gastroenterologists (82%) and GI registrars (79%), compared with non-GI
      consultants (74%), non-GI registrars (72%) and SHOs/interns (68%). Among
      gastroenterologists and GI registrars, knowledge levels of oesophageal (89%, 85%)
      and gastroduodenal applications (92%, 95%) was best while knowledge of colorectal
      applications (75%, 71%) was poorest. GI consultants and GI registrars display
      good knowledge of appropriate EUS indications although their knowledge of
      applications for colorectal disease is poorest. Future studies focusing on the
      education of non-gastroenterologists of the role of EUS would be helpful.

PMID- 19405320
TI  - Acute colonic obstruction due to benign prostatic hypertrophy.
AB  - A seventy two year old man presented to the Emergency Department with clinical
      features of colonic obstruction. Subsequent radiological investigations confirmed
      this impression and revealed the aetiology to be compression of the sigmoid colon
      against the sacrum by a massively distended urinary bladder. Chronic urinary
      retention due to benign prostatic hypertrophy is an extremely unusual cause of
      large bowel obstruction. Little in this patient's clinical findings suggested
      this aetiology. We reviewed the literature in this area and highlight the
      benefits of CT scanning over contrast studies.

PMID- 19405321
TI  - Merkel cell carcinoma metastasis to the iris in a 23 year old female.
AB  - Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine malignancy which
      predominantly affects elderly caucasians. The pathogenesis is poorly understood
      but ultraviolet light and immunosuppression have both been implicated. MCC most
      commonly arises on sun exposed areas of the head and neck or extremities and has
      a propensity for local recurrence and regional lymph node metastasis. It may
      present as a violaceous or non specific firm nodule or as a small plaque.
      Histological diagnosis can be difficult and electron microscopy or
      immunohistochemistry are frequently required in addition to light microscopy.
      Management is stage dependant and frequently involves wide surgical excision with
      or without chemotherapy or radiation therapy. Early diagnosis and complete
      surgical excision is associated with a favourable prognosis. However, aggressive
      tumours with regional recurrence or distant metastases result in a median
      survival of 9 months. Reports of primary MCC of the eyelids have been reported in
      the literature. Intra-ocular metastases to the choroid and ciliary body have also
      been reported.

PMID- 19405322
TI  - Berry syndrome in association with familial limb malformation.
AB  - We describe a newborn boy diagnosed with Berry syndrome consisting of a distal
      aortopulmonary septal defect, aortic origin of the right pulmonary artery, and
      interruption of the aorta. The child was noted to have reduplication of the right
      thumb. The child's mother had a claw malformation of her left hand but a normal
      cardiovascular status. Genetic analysis for TBX5 and SALL4 mutations were
      negative in both the patient and his mother. This case describes the first ever
      report of Berry syndrome in an infant with reduplication of the right thumb and
      familial limb malformation.

PMID- 19405323
TI  - First Irish pregnancies after IVF with gestational carrier.
AB  - In this report, our early experience with screening, monitoring and coordinating
      IVF utilising gestational carrier treatment is described. Although congenital and
      iatrogenic etiologies for uterine factor infertility manifest distinctly
      different reasons for considering a gestational carrier approach, we outline a
      unified management strategy for both conditions. One patient had congenital
      absence of the uterus and proximal vagina (Mayer-Rokitansky-Kuster-Hauser
      syndrome variant), while another patient presented post-hysterectomy and adjuvant
      brachytherapy for invasive squamous cervical carcinoma. Conception was
      established for both patients, the first pregnancies to be achieved using an
      IVF/gestational carrier technique in Ireland. As demonstrated here, selected
      patients with at least one intact ovary who suffer from uterine factor
      infertility can be excellent candidates for IVF with embryo transfer to a
      carefully screened gestational carrier. The role of individual and group
      counselling is reviewed; professional legal advice is prudent in complex cases.

PMID- 19405324
TI  - Iliopsoas abscess: a re-emerging clinical entity not to be forgotten.
AB  - Iliopsoas abscesses are relatively rare clinical entities. They present with
      subtle and non-specific symptoms and as a result the diagnosis is often delayed,
      leading to significant morbidity and mortality. With an increasing number of
      immunocompromised patients in the population the prevalence of this condition is
      set to rise. Therefore, early diagnosis and appropriate management remain a
      challenge for clinicians. We present three patients with iliopsoas abscesses, two
      of which were primary and one of which was secondary to Crohn's disease. The
      average age of patients was 59 years and both patients with primary psoas
      abscesses were male. All presented with non-specific symptoms. Psoas sign was
      present in only one patient. CT confirmed the diagnosis in all cases. Treatment
      consisted of appropriate antibiotic cover and associated percutaneous drainage.
      The psoas abscess that was secondary to underlying Crohn's disease was
      subsequently treated with surgical excision of the affected segment of bowel and
      lavage of the abscess cavity. A high index of suspicion is required to ensure the
      accurate and early diagnosis of this rare clinical entity. Abdominal CT scanning
      remains the gold standard for diagnosis. Management is with appropriate
      antibiotics and adequate drainage. This can be achieved by either percutaneous or
      surgical drainage. Such treatment can reduce the overall morbidity and mortality
      of this condition.

PMID- 19405325
TI  - Allowances for training.

PMID- 19405326
TI  - Thrombosis and psychosis--possible association with the antiphospholipid syndrome
      and anticardiolipin antibodies.

PMID- 19405327
TI  - Accidental ecstasy ingestion in a two year old.

PMID- 19405328
TI  - Network. Why being a practising depressive needn't preclude you from developing
      that leadership quality.

PMID- 19405329
TI  - ROTEM analysis: a significant advance in the field of rotational
      thrombelastography.
AB  - At the turn of the century, a significant advance in the rapidly expanding field
      of rotational thrombelastography (ROTEG), known at present as thrombelastometry
      or ROTEM analysis, was developed at the Ludwig-Maximillian University in Munich.
      The measuring unit is operated by a laptop computer. There are four temperature
      controlled measuring channels in which the global assays not only detect
      coagulation factor defects but also platelet function, abnormal fibrinogen
      polymerisation, anticoagulant defects and hyperfibrinolysis. ROTEM has steadily
      increased in popularity, particularly because of its well-established application
      as a diagnostic aid at the point of care in the critical care situation. It also
      provides a useful guide in the choice of an appropriate therapeutic option in the
      bleeding patient, reducing costs by avoiding administration of costly component
      therapy such as fresh-frozen plasma, cryoprecipitate, platelet concentrates or
      antifibrinolytic agents. As well as being useful in monitoring anticoagulant
      therapy and the use of pharmacological agents, ROTEM is a valuable research tool
      in the field of hypercoagulability, fibrinolysis, factor XIII activity and the
      ultimate phases of the blood coagulation process.

PMID- 19405330
TI  - Risk of blood splashes to the eye during surgery.
AB  - BACKGROUND: With the advent of a new infectious era involving the HIV and
      hepatitis B and C viruses, concern has arisen about transmission of these viruses
      through ocular blood splashes during surgery. The purpose of the study was to
      determine the risk of ocular blood splashes to surgeons and their assistants
      during surgery. METHOD: Surgeons and assistants in several surgical disciplines
      were requested to wear facemasks with a transparent plastic visor. The visors
      were collected postoperatively and inspected for macroscopic and microscopic
      blood splashes. RESULTS: Fifty-nine per cent of the surgeons and assistants
      refused to wear facemasks with a visor. The incidence of blood splashes in those
      who participated was 45%. There was a trend for blood splashes to be more common
      during major surgery and during elective surgery. Surgeons and assistants were
      subject to similar risk. CONCLUSION: This study confirms the significant risk of
      ocular blood splashes during surgery, while also suggesting that both surgeons
      and assistants lack appreciation of the risk.

PMID- 19405331
TI  - Antibiotic prophylaxis for patients undergoing elective endoscopic retrograde
      cholangiopancreatography. A survey of South African endoscopists and review of
      the literature.
AB  - BACKGROUND: Antibiotic prophylaxis for endoscopic retrograde
      cholangiopancreatography (ERCP) is controversial. We set out to assess the
      current antibiotic prescribing practice among South African endoscopists who
      perform ERCPs, and then reviewed international guidelines and relevant studies.
      METHODS: Our audit of South African endoscopists who perform ERCPs took the form
      of a questionnaire. For the literature review a Pubmed search was performed from
      1978 to March 2008, and these findings were compared with the current practice in
      South Africa. RESULTS: No specific protocols were being implemented widely in
      South Africa, and there was a marked difference in the practice between surgical
      and medical gastroenterologists, with surgeons using antibiotics more often.
      There was also a wide spectrum of antibiotic types that were being used. The
      Pubmed search revealed only 7 randomised controlled trials, with little consensus
      between them as to the absolute indications for prophylactic antibiotics in ERCP.
      CONCLUSIONS: Guidelines on antibiotic prophylaxis for ERCP are based on poor
      evidence. Varied opinions on its indications in South Africa may reflect the
      situation in other countries as well.

PMID- 19405332
TI  - Laparoscopic repair of Morgagni diaphragmatic hernia in children.
AB  - Minimal invasive surgery allows for excellent visualisation of the diaphragm, and
      is increasingly used for the repair of diaphragmatic hernias in children. This
      report describes laparoscopic repairs between 2001 and 2007 of four Morgagni
      hernias in children. All defects were treated successfully using the laparoscopic
      method, with no recurrences. The laparoscopic method is an ideal way to treat
      this type of diaphragmatic hernia.

PMID- 19405333
TI  - Preduodenal portal vein: a potential laparoscopic cholecystectomy nightmare.
AB  - Variations of biliary anatomy are well described. Those of most relevance to the
      operative surgeon are the variations of the extrahepatic ducts and their
      relationships to the right hepatic artery and its branches. We describe another
      even rarer congenital anomaly of a preduodenal portal vein. Its embryological
      derivation and presentation are discussed to heighten awareness of its
      recognition and reduce the potential of a serious operative misadventure.

PMID- 19405334
TI  - Tuberculosis resembling a malignant tumour.

PMID- 19405335
TI  - MDT's five-minute interview.

PMID- 19405336
TI  - The delicate balancing act of metallic biomaterials.
AB  - Ever since metals have been used within the human body, there has been
      controversy over whether they do harm as well as good. There is now another
      dimension to this issue provided by experiences with recent metal-on-metal hip
      replacements.

PMID- 19405337
TI  - Implications of material selection on the design of packaging machinery.
AB  - Material selection has significant implications on the design and cost of
      horizontal-form-fill-seal packaging machinery. To avoid excessive costs, machine
      redesigns and project delays, material selection must be reconciled early in the
      project and revisited throughout the construction of the machine.

PMID- 19405338
TI  - Micro moulding: the route to a successful product.
AB  - This account of a company's struggle to take its product from concept to market
      reality details how micro moulding techniques can help meet difficult design
      requirements and create successful products with increased output.

PMID- 19405339
TI  - Novel alloy for speciality needle applications.
AB  - A novel cobalt-chromium (CoCr) based alloy, optimised for speciality needle
      applications, has been benchmarked against Type 304 stainless steel in a series
      of mechanical test and experimental needle trials. The results reported indicate
      that the CoCr alloy has the potential to overcome current limitations in
      endoscopic and minimally invasive surgery.

PMID- 19405340
TI  - Avoiding surprises when implementing a single quality system.
AB  - European medical device manufacturers are sometimes surprised to learn that
      operating ISO 13485 alone is not sufficient to meet United States (US) quality
      system requirements. This article discusses important considerations for meeting
      US and European requirements when operating under a single quality system.

PMID- 19405342
TI  - [Death in media prime time. "A beautiful death honors the whole life".
      (Italian)].

PMID- 19405343
TI  - [Spasticity defied].

PMID- 19405341
TI  - Use of polymeric materials in orally inhaled and nasal drug products.
AB  - To maintain a high standard of quality in the materials and components used in
      the container systems of orally inhaled and nasal drug products, manufacturers
      need to collaborate closely with all those in the supply chain. Best practices in
      information sharing, particularly in relation to change control, are outlined
      here.

PMID- 19405344
TI  - [Neglect of infants and children as a form of child abuse].

PMID- 19405345
TI  - [Use of a probiotic in nosocomial infection: no effect in pediatric intensive
      care patients].

PMID- 19405346
TI  - [Delegating medical responsibilities to nurses--allowed by law?].

PMID- 19405347
TI  - [Hearing loss in childhood--questions for pediatric audiology].

PMID- 19405348
TI  - [The BeKD (German Professional Society of Pediatric Nursing) included in the
      "early intervention" program].

PMID- 19405349
TI  - [Faculty for nursing careers--how does the future look?].

PMID- 19405350
TI  - [Retinopathy of prematurity].
AB  - Retinopathy of prematurity (ROP) is a complex disease of the developing retinal
      vasculature in premature infants. Clinical manifestations range from mild,
      usually transient changes of the peripheral retina to severe progressive
      vasoproliferation, and potentally blinding retinal detachment. With better
      standards in premature units and with increased survival rate of low gestational
      age and low birth weight infants the incidence of ROP also increased. The
      incidence of ROP has been decreasing in developed countries over the past decade,
      and ROP has become potentially confined to immature neonates with birth weights
      less than 1000 grams in these countries. Prematurity and retinal immaturity are
      the major risk factors. Oxygenation, respiratory distress, apnea, bradycardia,
      hearth disease, infection, hypercarbia, acidosis, anemia, and the need for
      transfusion are thought by some to be contributory factors. All of the preterm
      babies with a birth weight under 1500 grams and a gestational age under 32 weeks
      should be followed for ROP.

PMID- 19405351
TI  - [Comment on "Natural healing in nursing. I. Aromatherapy"].

PMID- 19405352
TI  - [Revision of the nursing care need concept: only the beginning of a comprehensive
      nursing reform].

PMID- 19405353
TI  - [Delayed motherhood].

PMID- 19405354
TI  - Lives in the balance.

PMID- 19405355
TI  - Restoring the magic.

PMID- 19405356
TI  - Before you sign . . .

PMID- 19405357
TI  - Do you have an assisted-suicide plan?

PMID- 19405358
TI  - Stimulus saves Medicaid, but nobody's celebrating.

PMID- 19405360
TI  - Despite recession, doc outlook remains bright.

PMID- 19405359
TI  - Metabolic agents lead in total dollars spent.

PMID- 19405362
TI  - Changing culture to support wellness. Interview by John Marcille.

PMID- 19405361
TI  - Million-dollar claim club.

PMID- 19405363
TI  - Modern cardiovascular programs cut costs, inpatient days, and deaths.

PMID- 19405364
TI  - Plans and physicians in Hawaii experiment with online 'visits'.

PMID- 19405365
TI  - Providers enlisted to curtail waste.

PMID- 19405366
TI  - Cigna's CDHP study bolsters prevention.

PMID- 19405367
TI  - Part D plans embrace specialty drug tiers.

PMID- 19405368
TI  - The pursuit of happy docs.

PMID- 19405369
TI  - Transgenic goats are key to antithrombin production.

PMID- 19405370
TI  - Public spending on health care to accelerate.

PMID- 19405371
TI  - Clinical Centers of Excellence. Gynecologic oncology.

PMID- 19405372
TI  - Clinical Centers of Excellence. Gynecologic oncology. Duke University Medical
      Center.

PMID- 19405373
TI  - Clinical Centers of Excellence. Gynecologic oncology. University of Texas M.D.
      Anderson cancer center.

PMID- 19405374
TI  - Clinical Center of Excellence. Gynecologic oncology. Cedars-Sinai medical center.

PMID- 19405375
TI  - Clinical centers of Excellence. Gynecologic oncology. Yale cancer center.

PMID- 19405376
TI  - A tangled web.

PMID- 19405377
TI  - Suffering in silence.

PMID- 19405378
TI  - When religious beliefs collide with medicine.

PMID- 19405379
TI  - Effect of Emblica officinalis (Gaertn) on lens regeneration in the frog, Rana
      cyanophlyctis (Schneider).
AB  - Emblica officinalis (Amla) accelerated cell proliferation and dedifferentiation
      of pigmented epithelial cells of dorsal iris and consequently induced lens
      regeneration in R. cyanophlyctis. Further it enhanced the percentage of lens
      regeneration not only in young tadpoles but also is adult frogs. Lens
      regeneration ability declined with the age of animals in both control as well as
      treated groups.

PMID- 19405380
TI  - Hepato and reno protective action of Calendula officinalis L. flower extract.
AB  - Flower extract of C. officinalis L. was evaluated for its protective effect
      against CCl4 induced acute hepatotoxicity and cisplatin induced nephrotoxicity.
      The activities of serum marker enzymes of liver injury like glutamate pyruvate
      transaminase (SGPT), glutamate oxaloacetate transaminase (SGOT) and alkaline
      phosphatase (ALP) which were increased by CCl4 injection was found to be
      significantly reduced by the pretreatment of the flower extract at 100 and 250
      mg/kg body weight. The lipid peroxidation in liver, the marker of membrane damage
      and the total bilirubin content in serum were also found to be at significantly
      low level in the extract pretreated group, indicating its protective role. The
      kidney function markers like urea and creatinine were significantly increased in
      cisplatin treated animals. However, their levels were found to be lowered in the
      extract pretreated groups (100 and 250 mg/kg body weight). Moreover, cisplatin
      induced myelosuppression was ameliorated by the extract pretreatment. Treatment
      with the extract produced enhancement of antioxidant enzymes--superoxide
      dismutase and catalase and glutathione. Results suggest a protective role of the
      flower extract of C. officinalis against CCl4 induced acute hepatotoxicity and
      cisplatin induced nephrotoxicity. Extract has been found to contain several
      carotenoids of which lutein, zeaxanthin and lycopene predominates. Possible
      mechanism of action of the flower extract may be due to its antioxidant activity
      and reduction of oxygen radicals.

PMID- 19405382
TI  - Effect of conventional antihypertensive drugs on hypolipidemic action of garlic
      in rats.
AB  - The present study was undertaken to determine the possible alteration in
      hypolipidemic actions of garlic homogenate (GH) in presence of conventional
      antihypertensive drugs, propranolol (PRO), hydrochlorothiazide (HYD) and
      captopril (CAP). Albino rats fed with normal fat diet (NFD) or high fat diet
      (HFD) were treated with GH at three different doses (125, 250 and 500 mg/kg)
      orally for 30 days or in combination with PRO (10 mg/kg, po), HYD (10 mg/kg, po)
      and CAP (30 mg/kg, po) during last 7 days of GH treatment. After the treatment,
      total cholesterol (TC), LDL-cholesterol, triglyceride (TG) and HDL-cholesterol
      were measured in serum and antiatherogenic index was calculated. The result
      showed that moderate and high doses of GH possessed potential antiatherosclerotic
      property that was significantly attenuated by PRO and HYD. However, GH
      antihyperlipidemic activity was augmented by CAP. It was concluded that
      administration of PRO and HYD decrease the hypolipidemic effect of GH and
      administration of GH along with CAP augmented the hypolipidemic effect of GH in
      rats.

PMID- 19405381
TI  - Antiatherogenic and antiperoxidative effects of garlic and soy proteins in
      alcohol fed rats.
AB  - Rats fed with alcohol (18%) at 3.76 g/day for 45 days showed significant
      reduction in body weight, glutathione (GSH) content and activities of superoxide
      dismutase (SOD) and catalase in liver. Lecithin cholesterol acyltransferase
      (LCAT) in plasma, levels of HDL cholesterol in serum, hepatic bile acid
      production and fecal excretion of neutral sterols also showed significant
      reduction. Simultaneous feeding of garlic protein (GP) or soy protein (SP) (500
      mg/kg body weight/day for 45 days) to alcohol fed groups increased each of above
      parameters significantly towards normal values. Increase in GSH content and
      catalase activity in liver, was significantly higher for SP treated group than
      for GP treated group. However, increase in plasma LCAT was significantly higher
      for GP treated group than for SP treated group. Alcohol fed rats showed
      significant increase in liver weight, serum and tissue cholesterol, serum
      triacylglycerol (TAG), phospholipids (PL) and free fatty acid (FFA) levels and
      activity of HMGCoA reductase in liver and intestine. Lipid peroxidation, glucose
      6 phosphate dehydrogenase (G6PD), glutathione peroxidase (GPx) and glutathione
      reductase (GR) in liver and incorporation of labeled acetate into liver
      cholesterol also showed significant increase. GP and SP treated rats showed
      decrease in these values towards normal. GP feeding showed a better effect than
      SP in lowering serum and heart total cholesterol, and in maintaining GPx at near
      normal level, while SP feeding showed a better effect in lowering serum FFA level
      and maintaining GR activity at near normal level. In suppressing incorporation of
      labeled acetate into serum cholesterol, GP feeding showed a better effect than
      SP. Antiatherogenic and antiperoxidative effects of these proteins may be due to
      lower lysine/arginine ratio.

PMID- 19405383
TI  - Lipid lowering activity of ethanolic extract of leaves of Aegle marmelos (Linn.)
      in hyperlipidaemic models of Wistar albino rats.
AB  - Lipid lowering effect of 50% ethanolic extract of the leaves of A. marmelos
      (Linn.) was evaluated in triton and diet induced hyperlipidaemic models of Wistar
      albino rats. The extract at 125 and 250 mg/kg dose levels inhibited the elevation
      in serum cholesterol and triglycerides levels on Triton WR 1339 administration in
      rats. The extract at the same dose levels significantly attenuated the elevated
      serum total cholesterol and triglycerides with an increase in the high-density
      lipoprotein cholesterol in high-fat diet- induced hyperlipidaemic rats. The
      standard drugs atorvastatin in the former and gemfibrozil in the latter studies
      showed slightly better effects.

PMID- 19405384
TI  - Protective effect of Piper longum Linn. on monosodium glutamate induced oxidative
      stress in rats.
AB  - Protective effect of ethanol extract of Piper longum Linn. against monosodium
      glutamate (MSG) induced toxicity was studied. Rats, orally administered with MSG
      at a dose of 8 mg/g body weight for 20 consecutive days, showed an increase in
      liver weight and rate of lipid peroxidation. Glutathione (GSH) in serum, liver
      and kidney showed decreased concentration. Significant increase was noticed in
      activities of serum alanine amino transferase (ALT) and aspartate amino
      transferase (AST), levels of serum triacylglycerol, total cholesterol and urea.
      Histopathological examination of liver and kidney showed central venous
      congestion, diffuse degeneration and necrosis of hepatocytes in para cortical and
      midzonal areas of liver and diffuse cortical tubular degeneration of kidney. Oral
      administration of ethanol extract of P. longum fruits at 300 mg/kg body weight
      along with MSG significantly reduced the levels of lipid peroxides in serum,
      liver and kidney, serum AST activity, serum levels of triacylglycerol and total
      cholesterol. Though, there was an increase in the level of GSH in tissues it was
      not significant. However, the treatment failed to reduce the levels of ALT and
      urea. Examination of tissue sections also exhibited normal histological
      architecture of both the organs. The present study revealed that administration
      of P. longum provided significant protection to liver and kidney from the
      oxidative stress of MSG, though the dose rate was not sufficient to provide a
      complete protection.

PMID- 19405385
TI  - Anti-nociceptive effect of duloxetine in mouse model of diabetic neuropathic
      pain.
AB  - The involvement of adenosinergic pathway in the anti-nociceptive effect of
      duloxetine, a balanced 5-HT/NE reuptake inhibitor, was evaluated in
      streptozotocin induced diabetic male albino mice of Laca strain. After four weeks
      of single injection of streptozotocin (200 mg/kg, ip), mice were tested in the
      tail immersion and hot-plate assays. Cerebral adenosine levels were measured by
      high-performance liquid chromatography (HPLC/PDA detector). Diabetic mice
      exhibited significant hyperalgesia along with increased plasma glucose, decreased
      body weights and reduced cerebral adenosine levels. Administration of duloxetine
      (5, 10 and 20 mg/kg, ip) to diabetic mice produced dose-dependent anti
      nociceptive effect in both tail-immersion and hot-plate assays. Adenosine levels
      were also significantly and dose-dependently increased by different doses of
      duloxetine. The results demonstrated the involvement of adenosinergic pathway in
      duloxetine mediated anti-hyperalgesia in diabetic neuropathic pain.

PMID- 19405387
TI  - In vitro growth and shoot multiplication in Terminalia bellerica roxB. under
      controlled carbon dioxide environment.
AB  - The shoot cultures of Terminalia bellerica Roxb. were grown on Murashige and
      Skoog's medium containing 1.5 mg 1(-1) BAP (6- benzyl aminopurine), and
      supplemented with or without sucrose (3%). A range of CO2 concentrations (0.0,
      0.6, 10, 40 g(-3)) was provided in small acrylic chambers by using different
      concentrations and combinations of NaHCO3 (sodium bicarbonate), Na2CO3 (sodium
      carbonate), KHCO3 (potassium bicarbonate) and K2CO3 (potassium carbonate). To
      obtain a CO2-free environment, a saturated solution of 10% of KOH (potassium
      hydroxide) was kept in the chamber. Complete absence of carbon source caused
      death of shoots within 20 days. Under controlled and enriched CO2, the shoots
      grew fully photoautotropically on sucrose-free medium. The growth of cultures was
      better with carbon dioxide (40 g(-3)) than sucrose (3%) in the medium. Maximum
      number of shoots, number of leaves per cluster, fresh and dry weight and
      chlorophyll contents were recorded when both sucrose and CO2 (40 g(-3)) were
      provided to the culture.

PMID- 19405386
TI  - Role of PGrs and inhibitors in induction and control of somatic embryogenesis in
      Themeda quadrivalvis.
AB  - Somatic embryogenesis could be achieved in Themeda quadrivalvis (Linn.) O. Ktze 
      fodder grass species on MS medium supplemented with 2,4-D. Incorporation of
      putrescine in the medium stimulated embryogenesis, however its lower
      concentration stimulated production of non-regenerative callus. Other polyamines
      such as spermine and spermidine could not evoke similar response. Ascorbic acid
      used as antioxidant could not prevent browning in embryogenic cultures, however
      it stimulated embryogenesis. Inhibition of auxin polar transport by use of TIBA
      and HFCA reduced the embryogenic response significantly and produced distorted or
      abnormal embryos. Antiethylene substances such as AgNO3 and CoCl2 added in the
      medium adversely affected the process of embryogenesis and counteracting the
      stimulatory role of ethylene.

PMID- 19405388
TI  - Distribution and biodegradation of polycyclic aromatic hydrocarbons in
      contaminated sites of Hisar (India).
AB  - Fifty-two soil samples were collected from various location of the Hisar city.
      These samples were analysed for six polycyclic aromatic hydrocarbons
      (naphthalene, acenaphthene, phenanthrene, anthracene, fluoranthene, and pyrene).
      Total mean concentration of six PAHs varied from 51.79 to 148.82 mg kg(-1) dry
      weight of the soil, PAH concentration was higher in soil samples from local auto
      market while lower concentration was recorded in agricultural soil. Effect ofpH
      (5.0 to 9.0), temperature (20 degrees to 40 degrees C), and concentration of PAHs
      (5 to 20 mg kg(-1)) on biodegradation were optimized. Biodegradation of
      phenanthrene (3-ring) and pyrene (4-ring) was evaluated using two acclimatized
      microbial strains Pseudomonas putida and Pseudomonas paucimobilis. Biodegradation
      was maximum in sterilized artificial spiked soil with phenanthrene (5 mg kg(-1))
      and pyrene (5 mg kg(-1)) at pH 7.0 and at 30 degrees C (optimized conditions)
      than the native unsterilized contaminated soil (without optimized conditions) in
      42 days of incubation period with Pseudomonas putida and Pseudomonas
      paucimobilis. Phenanthrene was completely disappeared after 28 days with P.
      putida and after 35 days with P. paucimobilis. Whereas, pyrene was disappeared up
      to 97.40% with P. putida and 95.5% with P. paucimobilis after 42 days incubation
      period at optimum conditions. Under unoptimized conditions, disappearance of
      phenanthrene was 65.89% with P. putida and 57.81% with P. paucimobilis after 42
      days, whereas the % disappearance of pyrene was 59.80% with P. putida and 52.07%
      with P. paucimobilis.

PMID- 19405389
TI  - Antimicrobial activity of endemic Digitalis lamarckii Ivan from Turkey.
AB  - Antimicrobial activity of the methanolic extracts of leaves and flowers of D.
      lamarckii Ivan, (Scophulariaceae), an endemic plant species of Turkey, was tested
      on ten bacterial and four yeast strains. Effective antibacterial activity was
      observed in four bacterial strains. Minimum inhibitory concentration (MIC) was
      calculated by use of liquid culture tests and in all the four effective bacterial
      strains, the MIC was found to be > or = 199.5 mg/ml. The minimum bactericidal
      concentration (MBC) of B. subtilis, S. aureus, and L. monocytogenes was
      calculated to be > or = 199.5 mg/ml, and MBC value for Shigella was calculated as
      > or = 399 mg/ml.

PMID- 19405390
TI  - Shelf life and colonization of soil by clay based cyanobacterial inocula.
AB  - Four heterocystous cyanobacteria, isolated from grasslands of Ujjain were
      selected to prepare the clay based inoculants. Inoculants were evaluated for
      shelf life in terms of the titer value at 6 month intervals for 24 months. For
      colonization by inoculants in natural grasslands, the clay based inocula were
      applied to the field at: 40, 80 and 120 kg/ha and their survival was estimated at
      different time interval. Fuller's earth based inoculants had showed 50-65%
      survival after two year storage. After showing an initial decline, the population
      of the inoculated cyanobacteria became stable after 3 months. The inoculated
      strains persisted in the soil for longer duration, even after four months, their
      population was about 10-70 times higher than that of the uninoculated plots.

PMID- 19405391
TI  - Time for some remedies. As the health reform debate heats up, primary care must
      remain a top-tier issue.

PMID- 19405394
TI  - Paying by the bundle. Docs, hospitals 'at risk' under new CMS demo.

PMID- 19405395
TI  - By the numbers. Largest master's programs in health administration.

PMID- 19405396
TI  - [Surgical treatment of esophageal rupture of different localization].
AB  - The results of treatment of 37 patients, suffering esophageal rupture (ER), which
      had occurred due to foreign body perforation, thoracic and neck trauma
      consequences, iatrogenic damage, chemical burn perforation, and 12 patients with
      Boehrhaave syndrome, are presented. The complex of roentgenological methods was
      applied for the ER investigation. Surgical methods and operative accesses,
      depending on the esophageal damage level, are depicted. The esophageal lower
      third rupture constitutes the most prognostically unfavorable one.

PMID- 19405397
TI  - [The newly occurred and recurrent gastric ulcers after organ-preserving
      operations for the ulcer disease].
AB  - The literature data and the results of own investigations on gastric recurrent
      ulcers occurrence after organpreserving operations performance for the ulcer
      disease are summarized. The data on gastric recurrent ulcers occurrence rate are
      adduced. Modern views on possible causes of occurrence, necessary volume and
      informativity of investigation methods and tactics of treatment are presented.
      Gastroduodenal motor-evacuation function disorders, duodenogastric reflux and
      gastric hypersecretion are suggested as a most frequent causes of gastric
      recurrent ulcers occurrence. The method of operative intervention choice for
      recurrent gastric ulcer is determined by the cause of its occurrence, as well as
      the character of ulcer complication and the kind of previous surgical procedure
      performed.

PMID- 19405399
TI  - [The tactics choice for endoscopic bile ducts sanation in choledocholithiasis].
AB  - The results of treatment of 1420 patients, suffering choledocholithiasis, are
      presented. Three degrees of complicity of biliary ducts endoscopic sanation (ES)
      performance, depending on concrement diameter and pancreatic part of common
      biliary duct diameter ratio, were delineated. Differentiated tactics of
      treatment, depending on ES complexity, with predominant performance of
      transpapillary endoscopic interventions and lithotripsy, was elaborated.
      Application of the elaborated tactics of treatment had promoted lowering of the
      ES failure rate in 1.6 times, complications rate -- in 2.2 times and lethality --
      in 1.5 times.

PMID- 19405398
TI  - [Ultrasonographic diagnosis of hepatic polycystosis and the place of
      transcutaneous interventions under ultrasonographic guidance during palliative
      treatment].
AB  - The hepatic polycystosis (HPC) signs are studied up and the disease course stages
      are formulated. Transcutaneous puncture (TCP) under ultrasonographic
      investigation guidance with subsequent residual cavity sclerotherapy was applied
      in 53 patients as a method of palliative treatment of the disease. Indications
      for the method application, the procedure technique and tactics of the patients
      management were elaborated. The method of a staged treatment using periodical TCP
      conduction under ultrasonographic guidance was clinically introduced. Its
      efficacy was proved as a self-supporting method of palliative treatment of the
      disease in different stages. The best results were obtained after operative
      treatment for significant HPC in a compensation stage (the first stage--open or
      laparoscopic fenestration) with subsequent periodical TCP conduction (second
      stage - supportive treatment). Such combined tactics we consider the most
      effective method of HPC palliative treatment.

PMID- 19405400
TI  - [Results of surgical treatment of patients with subhepatic cholestasis of non
      tumor etiology].
AB  - There were studied the results, termed from 12 to 24 months, of operatively
      treated patients for subhepatic cholestasis of nontumoral etiology. The general
      clinical examination, ultrasonographic investigation were performed to the
      patients, as well as morphological changes estimation in hepatic fine-needle
      biopsies samples, biochemical indices and the state of systemic hepatic blood
      circulation. Application of complex staged operative interventions, added by
      hepatoregenerative operations, have had favored normalization of laboratory
      indices and structural hepatic changes as well as the hepatic blood supply
      improvement due to systolic inflow enhancement by 26% and microcirculatory bed
      blood circulation -- by 51%.

PMID- 19405401
TI  - [Application of ozone therapy in complex treatment of patients with acute
      necrotizing pancreatitis].
AB  - Examination and treatment of 32 patients was done, in whom an acute necrotic
      pancreatitis was diagnosed. In 16 patients (the main group) ozonotherapy,
      according to scheme, elaborated in the clinic, was added to conventional
      treatment. The ozonotherapy application had permitted to reduce the rate of
      performance of "open" operative interventions. The cellular, humoral and local
      immunity improvement and biochemical indices normalization were noted. The
      stationary treatment duration was 21.4 days at average in the main group and 34.5
      -- in a control one. The relaparotomy performance rate in the main group was
      lesser than in a control one.

PMID- 19405402
TI  - [The treatment of an acute paraproctitis].
AB  - The results of surgical treatment of an acute paraproctitis in 708 patients, in 9
      (1.27%) of whom gangrenous -- putrificated form of paraproctitis was diagnosed,
      are adduced. In 187 (42.6%) patients the abscess disclosure with intraintestinal
      purulent fistula, going into intestinal lumen, excision was performed, together
      with cryptectomy -- in 182 (41.4%), the ligature method was applied in 18 (4.1%)
      with subsequent fistula excision and its internal orifice plasty using mucosal
      submucosal flap. For extrasphincteric or transsphincteric purulent tunnel the
      abscess was opened and drained, its internal orifice sutured, using 'distant"
      removable suture. It internal orifice was not revealed there was accomplished
      procedure of disclosure and draining of purulent cavity, the wound sanation with
      insufflation of ozone-oxygen mixture. In anaerobic paraproctitis the procedure
      consisted of disclosure and draining of purulent cavities with necrectomy was
      performed. To all the patients antibacterial therapy was conducted. In 20 (4.5%)
      patients an acute paraproctitis recurrence had occurred, in 9 (2%) -- pararectal
      fistula, and in 5 (1.1%) -- the anal sphincter stage I insufficiency.

PMID- 19405404
TI  - [Surgical correction of tubular breast deformities].
AB  - The results of tubular chest surgical correction in 24 patients--women were
      analyzed. Differentiated approach to the operative treatment method choice was
      applied, depending on the chest volume and tubularity type. Positive aesthetic
      result was achieved.

PMID- 19405403
TI  - [Peculiarities of the venous bed vessels reconstruction while performing liver
      transplantation from live relative donor in children].
AB  - The rate of hepatic transplantation from live relative donor in children is
      increasing in all over the world and in Ukraine as well. Significant incidence of
      the pathology together with necessity of technically complex intervention
      performance causes the need for surgical technique improvement, a new methods
      elaboration and clinical introduction, permitting to lower the postoperative
      complications rate. Technical complexity constitutes the main peculiarity of
      transplantation operation of liver, obtained from live relative donor, in
      children, it is caused by the vessels small diameter, pathological changes of the
      recipient portal vein and lack of plastic material for reconstruction of vessels.
      There are proposed various plastic methods for the transplant portal inflow and
      venous outflow guaranteeing to achieve a success while performing left lateral
      hepatic section transplantation, permitting to improve the results of hepatic
      transplantation from live relative donor in children.

PMID- 19405405
TI  - [Maximal removal of pathogenic microorganisms and their toxins from abdominal
      cavity in patients with extended purulent peritonitis after the operation].
AB  - The efficacy was analyzed and comparative estimation of the results was done,
      based on investigation, conducted in 63 laboratory animals and 30 patients,
      suffering extended purulent peritonitis, in whom a new method of abdominal cavity
      sanation was applied, using the "sac" made of polyvynilpirrolidon shell and
      homemade coal-mineral adsorbent UM--5 for enterodetoxication in complex of
      treatment after the operation. Maximal removal of microorganisms and their life
      activities products from abdominal cavity and small intestine lumen, the adhesive
      process and interintestinal abscesses elimination, the intoxication severity
      reduction were promoted by a new approach application.

PMID- 19405407
TI  - Multimodal treatment of attention-deficit/hyperactivity disorder in children.

PMID- 19405406
TI  - [The role of videothoracoscopy in diagnosis and treatment of metastatic tumoral
      pleuritis].
AB  - The experience of diagnosis and treatment of 108 patients, suffering malignant
      metastatic exudative pleuritis, is presented. Different variants of
      pleuropulmonary biopsy, performed under local anesthesia and narcosis, are
      suggested. Special attention is dedicated to various methods of pleurodesis,
      performed as a variant of palliative treatment and prophylaxis of exudation.
      Comparative characteristics on efficacy of various methods of pleurodesis and the
      others are adduced. Simple methods, using chemopreparations, must be preferred
      while choosing the pleurodesis method. All the patients are alive.

PMID- 19405408
TI  - Treatment of otitis media with perforated tympanic membrane.

PMID- 19405409
TI  - Current strategies in the diagnosis and treatment of childhood attention
      deficit/hyperactivity disorder.
AB  - Symptoms of childhood attention-deficit/hyperactivity disorder affect cognitive,
      academic, behavioral, emotional, social, and developmental functioning. Attention
      deficit/hyperactivity disorder is the most commonly diagnosed neurodevelopmental
      disorder in children and adolescents. An estimated 2 to 16 percent of school-aged
      children have been diagnosed with the disorder. The prevalence of attention
      deficit/hyperactivity disorder in the primary care setting is similar to that in
      the general community, depending on the diagnostic criteria and population
      studied. The causality of attention-deficit/hyperactivity disorder is relatively
      unknown. Most recent studies focus on the role of dopamine; norepinephrine; and,
      most recently, serotonin neurotransmitters. The disorder is classified into three
      general subtypes: predominantly hyperactive-impulsive, predominantly inattentive,
      and combined. Screening tools and rating scales have been devised to assist with
      the diagnosis. Appropriate treatment can dramatically improve the function and
      quality of life of the patient and family. Pharmacologic treatment includes
      stimulants, such as methylphenidate and mixed amphetamine salts, or
      nonstimulants, such as atomoxetine. Behavioral approaches, particularly those
      that reward desirable behavior, are also effective. A combination of
      pharmacologic and behavioral therapies is recommended.

PMID- 19405410
TI  - Evaluating and understanding articles about treatment.
AB  - Each year physicians must decide which of the thousands of newly published
      articles they will take time to read. To determine which articles are the most
      clinically useful, physicians should assess their relevance, validity, and
      clinical importance. Using these criteria can drastically decrease the number of
      articles physicians need to read.

PMID- 19405411
TI  - Drug treatments for polycystic ovary syndrome.
AB  - Polycystic ovary syndrome is a condition present in approximately 5 to 10 percent
      of women of childbearing age. Diagnosis can be difficult because the signs and
      symptoms can be subtle and varied. These may include hirsutism, infertility,
      menstrual irregularities, and biochemical abnormalities, most notably insulin
      resistance. Treatment should target specific manifestations and individualized
      patient goals. When choosing a treatment regimen, physicians must take into
      account comorbidities and the patient's desire for pregnancy. Lifestyle
      modifications should be used in addition to medical treatments for optimal
      results. Few agents have been approved by the U.S. Food and Drug Administration
      specifically for use in polycystic ovary syndrome, and several agents are
      contraindicated in pregnancy. Insulin-sensitizing agents are indicated for most
      women with polycystic ovary syndrome because they have positive effects on
      insulin resistance, menstrual irregularities, anovulation, hirsutism, and
      obesity. Metformin has the most data supporting its effectiveness. Rosiglitazone
      and pioglitazone are also effective for ameliorating hirsutism and insulin
      resistance. Metformin and clomiphene, alone or in combination, are first-line
      agents for ovulation induction. Insulin-sensitizing agents, oral contraceptives,
      spironolactone, and topical eflornithine can be used in patients with hirsutism.

PMID- 19405412
TI  - Risks and benefits of pacifiers.
AB  - Physicians are often asked for guidance about pacifier use in children,
      especially regarding the benefits and risks, and when to appropriately wean a
      child. The benefits of pacifier use include analgesic effects, shorter hospital
      stays for preterm infants, and a reduction in the risk of sudden infant death
      syndrome. Pacifiers have been studied and recommended for pain relief in newborns
      and infants undergoing common, minor procedures in the emergency department
      (e.g., heel sticks, immunizations, venipuncture). The American Academy of
      Pediatrics recommends that parents consider offering pacifiers to infants one
      month and older at the onset of sleep to reduce the risk of sudden infant death
      syndrome. Potential complications of pacifier use, particularly with prolonged
      use, include a negative effect on breastfeeding, dental malocclusion, and otitis
      media. Adverse dental effects can be evident after two years of age, but mainly
      after four years. The American Academy of Family Physicians recommends that
      mothers be educated about pacifier use in the immediate postpartum period to
      avoid difficulties with breastfeeding. The American Academy of Pediatrics and the
      American Academy of Family Physicians recommend weaning children from pacifiers
      in the second six months of life to prevent otitis media. Pacifier use should not
      be actively discouraged and may be especially beneficial in the first six months
      of life.

PMID- 19405414
TI  - Screening for bacterial vaginosis in pregnancy to prevent preterm delivery.

PMID- 19405415
TI  - White, opaque fluid in a blood draw. Hypertriglyceridemia.

PMID- 19405417
TI  - How Obama is using the science of change.

PMID- 19405416
TI  - It's high time.

PMID- 19405418
TI  - The new age of extinction.

PMID- 19405419
TI  - Better learning through fidgeting.

PMID- 19405420
TI  - My hopes and expectations for the next year.

PMID- 19405421
TI  - The advantage of converged systems.

PMID- 19405422
TI  - Revving up revenue.

PMID- 19405423
TI  - The big payoff.

PMID- 19405424
TI  - The road to effective RCM.

PMID- 19405425
TI  - Getting real with payers and patients.

PMID- 19405426
TI  - Time to punch-in.

PMID- 19405427
TI  - Reflections on 2008--forecast for 2009.

PMID- 19405428
TI  - The great buyback. Systems are repurchasing bonds priced to move.

PMID- 19405429
TI  - HHS: don't call on self-referrals. Inspector general's office narrows scope of
      disclosure.

PMID- 19405430
TI  - Time to collaborate. President's call requires willingness of all to compromise.

PMID- 19405431
TI  - Upon closer inspection. As the U.S. imports more drugs and devices, the FDA's
      overseas initiatives aim to head off trouble at the source.

PMID- 19405432
TI  - Stop the bleeding? Orthopedic surgeons split on merit of CMS VTE goals.

PMID- 19405433
TI  - By the numbers. Largest behavioral health providers.

PMID- 19405434
TI  - Strain distribution in the proximal human femoral metaphysis.
AB  - There is significant interest in the stress-strain state in the proximal femoral
      metaphysis, because of its relevance for hip fractures and prosthetic
      replacements. The scope of this work was to provide a better understanding of the
      strain distribution, and of its correlation with the different directions of
      loading, and with bone quality. A total of 12 pairs of human femurs were
      instrumented with strain gauges. Six loading configurations were designed to
      cover the range of directions spanned by the hip joint force. Inter-specimen
      variability was reduced if paired specimens were considered. The principal strain
      magnitude varied greatly between loading configurations. This suggests that
      different loading configurations need to be simulated in vitro. The strain
      magnitude varied between locations but, on average, was compatible with the
      strain values measured in vivo. The strain magnitudes and the direction of
      principal tensile strain in the head and neck were compatible with the
      spontaneous fractures of the proximal femur reported in some subjects. The
      principal tensile strain was significantly larger where the cortical bone was
      thinner; the compressive strain was larger where the cortical bone was thicker.
      The direction of the principal strain varied significantly between measurement
      locations but varied little between loading configurations. This suggests that
      the anatomy and the distribution of anisotropic material properties enable the
      proximal femur to respond adequately to the changing direction of daily loading.

PMID- 19405435
TI  - Advanced computer-aided design for bone tissue-engineering scaffolds.
AB  - The design of scaffolds with an intricate and controlled internal structure
      represents a challenge for tissue engineering. Several scaffold-manufacturing
      techniques allow the creation of complex architectures but with little or no
      control over the main features of the channel network such as the size, shape,
      and interconnectivity of each individual channel, resulting in intricate but
      random structures. The combined use of computer-aided design (CAD) systems and
      layer-manufacturing techniques allows a high degree of control over these
      parameters with few limitations in terms of achievable complexity. However, the
      design of complex and intricate networks of channels required in CAD is extremely
      time-consuming since manually modelling hundreds of different geometrical
      elements, all with different parameters, may require several days to design
      individual scaffold structures. An automated design methodology is proposed by
      this research to overcome these limitations. This approach involves the
      investigation of novel software algorithms, which are able to interact with a
      conventional CAD program and permit the automated design of several geometrical
      elements, each with a different size and shape. In this work, the variability of
      the parameters required to define each geometry has been set as random, but any
      other distribution could have been adopted. This methodology has been used to
      design five cubic scaffolds with interconnected pore channels that range from 200
      to 800 microm in diameter, each with an increased complexity of the internal
      geometrical arrangement. A clinical case study, consisting of an integration of
      one of these geometries with a craniofacial implant, is then presented.

PMID- 19405436
TI  - The biomechanics of the T2 femoral nailing system: a comparison of synthetic
      femurs withfinite element analysis.
AB  - Intramedullary nails are commonly used to repair femoral fractures. Fractures in
      normal healthy bone often occur in the young during motor vehicle accidents.
      Although clinically beneficial, bone refracture and implant failure persist.
      Large variations in human femur quality and geometry have motivated recent
      experimental use of synthetic femurs that mimic human tissue and the development
      of increasingly sophisticated theoretical models. Four synthetic femurs were
      fitted with a T2 femoral nailing system (Stryker, Mahwah, New Jersey, USA). The
      femurs were not fractured in order to simulate post-operative perfect union. Six
      configurations were created: retrograde nail with standard locking (RS),
      retrograde nail with advanced locking 'off' (RA-off), retrograde nail with
      advanced locking 'on' (RA-on), antegrade nail with standard locking (AS),
      antegrade nail with advanced locking 'off' (AA-off), and antegrade nail with
      advanced locking 'on' (AA-on). Strain gauges were placed on the medial side of
      femurs. A 580 N axial load was applied, and the stiffness was measured. Strains
      were recorded and compared with results from a three-dimensional finite element
      (FE) model. Experimental axial stiffnesses for RA-off (771.3 N/mm) and RA-on
      (681.7 N/mm) were similar to intact human cadaveric femurs from previous
      literature (757 + 264 N/mm). Conversely, experimental axial stiffnesses for AS
      (1168.8N/mm), AA-off (1135.3N/mm), AA-on (1152.1 N/mm), and RS (1294.0 N/mm) were
      similar to intact synthetic femurs from previous literature (1290 +/- 30 N/mm).
      There was better agreement between experimental and FE analysis strains for RS
      (average percentage difference, 11.6 per cent), RA-on (average percentage
      difference, 11.1 per cent), AA-off (average percentage difference, 13.4 per
      cent), and AA-on (average percentage difference, 16.0 per cent), than for RA-off
      (average percentage difference, 33.5 per cent) and AS (average percentage
      difference, 32.6 per cent). FE analysis was more predictive of strains in the
      proximal and middle sections of the femur-nail construct than the distal. The
      results mimicked post-operative clinical stability at low static axial loads once
      fracture healing begins to occur.

PMID- 19405437
TI  - The importance of a thick cement mantle depends on stem geometry and stem-cement
      interfacial bonding.
AB  - The thickness of the cement mantle around the femoral component of total hip
      replacements is a contributing factor to aseptic loosening and revision.
      Nevertheless, various designs of stems and surgical tooling lead to cement
      mantles of different thicknesses. Opinion is divided on whether a thick mantle
      enhances implant longevity. This study investigates the effect of cement mantle
      thickness on accumulated damage in the cement, and how this is influenced by the
      presence or absence of a proximal collar and on whether the stem-cement interface
      remains bonded. Three-dimensional finite element simulations incorporating creep
      and non-linear damage accumulation were performed to investigate cracking in the
      cement mantles around Stanmore Hips under physiologically informed stair-climbing
      and gait loads. Cement mantle thickness, stem-cement interfacial bonding, and
      collar design were varied to assess the interactive effects of these parameters.
      In all cases, damage levels were three to six times higher when the stem-cement
      interface remained bonded. Cement mantle thickness had little effect on cement
      damage accumulation around debonded collared stems but was critical in both
      bonded and collarless cases, where a thicker mantle reduced cement cracking.
      Damage around a smooth debonded stem with a collar is thus much less sensitive to
      cement thickness than around bonded or collarless stems.

PMID- 19405438
TI  - Minimal-resection arthroplasty to treat meniscal tears with associated condyle
      lesions: finite element analysis.
AB  - An early intervention prosthesis which minimizes the extent of resected healthy
      bone would be advantageous to patients for whom a total or unicompartmental
      replacement would sacrifice extensive healthy tissue. In this study the use of a
      device to treat osteoarthritis localized upon a single condyle of the femur with
      an associated irreparable meniscal tear is considered. The effects of implant
      alignment are considered from the standpoint of kinematics and potential for
      cartilage damage. The results suggest that alterations in implant position
      influence joint kinematics during stance. Anteroposterior (AP) adjustment of the
      medial prosthesis minimizes the capability of the knee to rotate internally,
      placing higher demands on the cruciate ligaments. AP adjustments of the lateral
      prosthesis induces greater posterior drawback, reducing internal-external
      rotation. Natural knee kinematics are best reproduced by the medial condyle
      rather than the lateral condyle. Stress exposure of the cartilage increased with
      the introduction of the femoral condyle prosthesis, which may progress eventually
      to osteoarthritis, although the results indicate that the medial condyle device
      is less likely to lead to cartilage damage than is lateral condyle replacement.
      This study demonstrates that a minimal-resection femoral condyle device may
      provide sufficient knee joint function to serve as an interim treatment prior to
      total or unicompartmental knee arthroplasty.

PMID- 19405439
TI  - Mechanical properties of bovine articular cartilage under microscale indentation
      loading from atomic force microscopy.
AB  - Atomic force microscopy (AFM) techniques have been increasingly used for
      investigating the mechanical properties of articular cartilage. According to the
      previous studies reporting the microscale Young's modulus under AFM indentation
      tests, the Hertz contact model has been employed with a sharp conical tip
      indenter. However, the non-linear microscale behaviour of articular cartilage
      could not be resolved by the standardized Hertz analysis using small and sharp
      atomic force microscope tips. Therefore, the objective of this study was to
      evaluate the microscale Young's modulus of articular cartilage more accurately
      through a non-Hertzian approach with a spherical tip of 5 microm diameter, and to
      characterize its microscale mechanical behaviour. This methodology adopted in the
      present study was proved by the consistent values between the microscale (2 per
      cent, about 9.3 kPa; 3 per cent, about 17.5kPa) and macroscale (2 per cent, about
      8.3kPa; 3 per cent, about 18.3kPa) Young's moduli for 2 per cent and 3 per cent
      agarose gel (n = 100). Therefore, the microscale Young's modulus evaluated in
      this study is representative of more accurate measurements of cartilage stiffness
      at the 600 nm deformation level and corresponds to approximately 30.9 kPa (n =
      100). Furthermore, on this level of the microscale deformation, articular
      cartilage showed depth-dependent and frequency-independent behaviour under AFM
      indentation loading. These findings reveal the microscale mechanical behaviour of
      articular cartilage more accurately and can be employed further to design
      microscale structures of chondrocyte-seeded scaffolds and tissue-engineered
      cartilage by evaluating their microscale properties.

PMID- 19405441
TI  - Median sternotomy: comparative testing of braided superelastic and monofilament
      stainless steel sternal sutures.
AB  - A new device to reduce the risk of post-operative complications following median
      sternotomy is proposed, made of a superelastic shape memory alloy and called a
      braided tubular superelastic (BTS) suture. This study compares the viability of
      the BTS suture with that of the standard monofilament stainless steel (MSS)
      suture. A custom test bench was developed to perform comparative testing of the
      two sternal closure systems. Sternal models made of polyurethane were closed
      using common wiring configurations. Static and dynamic tensile separation forces,
      up to a maximum of 1200 N, were then applied to the closed sternums. The MSS and
      BTS sutures are compared in terms of the force required to open completely the
      sternum, the compression force at the sternum midline, and the permanent sternum
      opening. With a smaller sternum opening and a higher tensile separation force,
      the MSS suture showed greater rigidity than the BTS suture. The BTS suture,
      however, displayed a better capacity to reapply compression forces at the sternum
      midline following the repetitive application and release of tensile separation
      forces. These results confirm the potential of the BTS suture technology, but
      further studies using cadaveric sterna are needed to attest definitely to the
      benefits of using the BTS suture to improve bone healing.

PMID- 19405440
TI  - Accuracy of digitization of bony landmarks for measuring change in scapular
      attitude.
AB  - Digitizing bony landmarks is a common technique used to measure scapular
      position, but it has not been validated against a gold standard. The aim of this
      study was to determine the accuracy of this technique for four physiological arm
      movements using optoelectronic markers mounted on scapular bone pins as a gold
      standard. Eight subjects had bone pins inserted into their lateral scapular
      spine. Three points were digitized on the scapula with an optoelectronic probe:
      the medial root of the scapular spine, the posterolateral corner of the acromion,
      and the inferior angle of the scapula. The four active movements tested in this
      study were glenohumeral abduction, glenohumeral horizontal adduction, hand behind
      back, and forward reaching. The three bony landmarks were digitized six times in
      three different positions for each movement. Data from one subject were rejected
      secondary to pin loosening. The overall position-specific r.m.s. errors ranged
      from 2.0 degrees to 12.5 degrees. The full abduction position had considerably
      higher r.m.s. errors than the other positions (posterior tipping, 12.5 degrees;
      upward rotation, 7.3 degrees; internal rotation, 12.0 degrees). It appears that
      the digitization of bony landmarks may be a valid method for measuring changes in
      scapular attitude with the following caveats: the full abduction position has a
      high r.m.s. error, and small scapular motions have high percentage errors.

PMID- 19405442
TI  - Detection of the furcation involvement of a multi-rooted molar using natural
      frequency analysis: a numerical approach.
AB  - The aim of this study was to evaluate the potential for using the natural
      frequency (NF) as a parameter to detect vertical bone loss at the furcation of
      human molars as well as to assess the role that the surrounding bone plays in
      maintaining molar stability. A three-dimensional finite element model of the
      human maxillary molar was built. The NF values of the molar modal were calculated
      with one-sided, two-sided, and three-sided vertical bone loss. It was found that
      the change in the NF was less than 25 per cent in molars with a one-sided defect
      when the bone level varied by 10 mm from the cementoenamel junction. However,
      when a three-sided bony defect was simulated, the change in the NF ranged from 40
      to 60 per cent. In addition, it was found that bone loss that had reached the
      furcation entrance (4 mm) resulted in a sharp change in the NF value.
      Furthermore, it was found that bone loss involving the mesial and distal surfaces
      resulted in a larger decrease in the NF value compared with bone loss involving
      the buccal and palatal surfaces. These results demonstrated that the bone
      surrounding the mesial and distal sides plays a more important role in
      maintaining molar stability than does the bone surrounding the buccal and palatal
      sides.

PMID- 19405443
TI  - The accuracy and precision of a micro computer tomography volumetric measurement
      technique for the analysis of in-vitro tested total disc replacements.
AB  - Total disc replacements (TDRs) in the spine have been clinically successful in
      the short term, but there are concerns over long-term failure due to wear, as
      seen in other joint replacements. Simulators have been used to investigate the
      wear of TDRs, but only gravimetric measurements have been used to assess material
      loss. Micro computer tomography (microCT) has been used for volumetric
      measurement of explanted components but has yet to be used for in-vitro studies
      with the wear typically less than < 20 mm3 per 10(6) cycles. The aim of this
      study was to compare microCT volume measurements with gravimetric measurements
      and to assess whether microCT can quantify wear volumes of in-vitro tested TDRs.
      microCT measurements of TDR polyethylene cores were undertaken and the results
      compared with gravimetric assessments. The effects of repositioning, integration
      time, and scan resolution were investigated. The best volume measurement
      resolution was found to be +/- 3 mm3, at least three orders of magnitude greater
      than those determined for gravimetric measurements. In conclusion, the microCT
      measurement technique is suitable for quantifying in-vitro TDR polyethylene wear
      volumes and can provide qualitative data (e.g. wear location), and also further
      quantitative data (e.g. height loss), assisting comparisons with in-vivo and ex
      vivo data. It is best used alongside gravimetric measurements to maintain the
      high level of precision that these measurements provide.

PMID- 19405444
TI  - [Morphofunctional organization of reserve stem cells providing for asexual and
      sexual reproduction of invertebrates].
AB  - Published and original data indicating evolutionary conservation of the
      morphofunctional organization of reserve stem cells providing for asexual and
      sexual reproduction of invertebrates are reviewed. Stem cells were studied in
      representatives of five animal types: archeocytes in sponge Oscarella malakhovi
      (Porifera), large interstitial cells in colonial hydroid Obelia longissima
      (Cnidaria), neoblasts in an asexual race of planarian Girardia tigrina
      (Platyhelmintes), stem cells in colonial rhizocephalans Peltogasterella gracilis,
      Polyascus polygenea, and Thylacoplethus isaevae (Arthropoda), and colonial
      ascidian Botryllus tuberatus (Chordata). Stem cells in animals of such diverse
      taxa feature the presence of germinal granules, are positive for proliferating
      cell nuclear antigen, demonstrate alkaline phosphatase activity (at marker of
      embryonic stem cells and primary germ cells in vertebrates), and rhizocephalan
      stem cells express the vasa-like gene (such genes are expressed in germline cells
      of different metazoans). The self-renewing pool of stem cells is the cellular
      basis of the reproductive strategy including sexual and asexual reproduction.

PMID- 19405446
TI  - [A study of protein profile changes in differentiating human myoblasts].
AB  - The changes in the protein profile in cultured human myoblasts after induction of
      differentiation was studied by proteomic techniques (a combination of O'Farrell
      two-dimensional electrophoresis and subsequent protein identification by MALDI
      TOF MS and MS/MS analyses). Forty-one proteins have been identified, 25 of which
      were present in both proliferating and differentiating myoblasts, which allows
      them to be considered as myoblast housekeeping proteins. The changes in the
      distribution of some isoforms of tropomyosins, S100 proteins, cofilin, etc. have
      been revealed. The possible role of these changes in the cell protein profile in
      the realization of the program of skeletal muscle cell differentiation is
      discussed.

PMID- 19405445
TI  - [Direct cell-cell communications and social behavior of cells in mammals,
      protists, and bacteria. Possible causes of multicellularity].
AB  - Comparison of current data on direct cell-cell communications in mammals,
      protists, and bacteria suggests that the emergence of the signaling systems of
      self-organization underlay the emergence of multicellular organisms. Biogenic
      amines, regulators of coordinated behavior and aggregation in bacteria, have been
      found in protists and multicellular organisms. In metazoans, biogenic amines have
      become specific neurotransmitters. At the same time, the studies on
      synchronization of protein synthesis rhythm in mammalian cell cultures
      demonstrated that noradrenaline and serotonin have conserved their ancient
      function of cell-cell cooperation in mammals, which is manifested as coordinated
      social behavior of cells in population in the case of bacteria and multicellular
      organisms.

PMID- 19405447
TI  - [An improved method of genomic in situ hybridization (GISH) for distinguishing
      closely related genomes of tetraploid and hexaploid wheat species].
AB  - An improved modification of genomic in situ hybridization (GISH) was proposed. It
      allows clear and reproducible discrimination between closely related genomes of
      both tetraploid and hexaploid wheat species due to preannealing of labeled DNA
      probes and prehybridization of chromosomal samples with blocking DNA. The method
      was applied to analyze intergenomic translocations 6A:6B and 1A:6B identified in
      the IG46147 and IG116188 samples of tetraploid wheat Triticum dicoccoides by C
      banding. The structure of the rearranged chromosomes was defined for two
      translocation variants, and the breakpoints were identified on the chromosome
      arms. Possible application of the developed GISH variant to study genome
      reorganizations during speciation of allopolyploid plants in evolution is
      discussed.

PMID- 19405448
TI  - [Circulatory system in chicken skeletal muscle in the second half of
      embryogenesis: shape, bloodstream, and vascular reactivity].
AB  - A restructuring of the capillary bed-from the embryonic structure with a three
      dimensional network of wide and long protocapillaries to the mature structure
      with high density of thin and short capillaries along the fibers-has been
      demonstrated in the chick skeletal muscle on embryonic days 10-19 by morphometric
      analysis. In this case, the volumetric flow rate and capillary luminal area per
      cm3 of the muscle remained unaltered, while the blood volume in it significantly
      dropped. The response of muscle circulation to nitroprusside (increase) and
      noradrenaline (decrease) appeared in 19-day-old embryos, but this response could
      develop only under conditions of initially low or high bloodstream, respectively.
      We propose that the arterial trunk lumen area to the total capillary lumen area
      remains constant as the intraorganic circulation is formed, which provides for
      the required linear blood velocity in capillaries.

PMID- 19405449
TI  - [How chicken embryo survives after half of shell is sealed?].
AB  - The goal of this study was to explore the development of the gas transport
      systems in chick embryos after half of the shell surface is closed on incubation
      day 11. By the end of day 3 of the experiment (incubation day 14), the vascular
      reduction in the chorioallantois under the covered zone is fully compensated by
      the vessel dilatation and growth in the intact half. In parallel, the oxygen
      capacity of blood elevates and hematopoiesis increases: the indices of
      hematocrit, hemoglobin, and erythrocyte count increase by half. The development
      of the left ventricular myocardium accelerates through the myocyte hyperplasia
      and their more mature ultrastructure. The obtained data indicate that hypoxia
      accelerates the embryonic development and leads to earlier and faster
      differentiation of the gas transport systems. However, the efficiency of
      antihypoxic responses is limited by the upper bound of capillary density in the
      chorionic respiratory network. After 1 week of the experiment (incubation day
      18), the total vascular volume in the chorioallantois is halved relative to
      control, while the arterial walls substantially thicken in the open part, which
      increases the peripheral resistance. Atherosclerosis and dystrophy of
      cardiomyocytes developed in the left ventricle. These general hemodynamic
      abnormalities are accompanied by a notable embryonic growth inhibition. Thus, the
      structural compensation of the gas transport systems in the experiment becomes
      exhausted and cannot provide for increasing metabolic demands of the growing
      embryo.

PMID- 19405451
TI  - [Qualifications of exotic nurses].

PMID- 19405452
TI  - [Global market for valuable nurses].

PMID- 19405450
TI  - [Mechanodependent cell movements in the axial rudiments of Xenopus gastrulae].
AB  - Sandwich explants of the suprablastoporal area of Xenopus early-mid gastrula and
      same stages of entire embryos were stretched with two needles perpendicular to
      the direction of natural elongation of the axial rudiments. The changes in the
      embryonic shape and histological structure were monitored as well as the
      arrangement of descendants of one of dorsal blastomers labeled with fluorescein
      dextran at the 16-cell stage. A substantial fraction of stretched explants
      reoriented along the applied stretch direction. The arrangement dynamics of
      fluorescein-dextran-labeled cells and explant shape demonstrate that this is an
      active response based on convergent intercalation of cells induced by stretching.
      Stretched gastrulae demonstrated arrested gastrulation, dorsoventral extension of
      the blastopore, and ventral flow of labeled cells towards the lateral lips of the
      blastopore, which was also mediated by convergent intercalation and tensotaxis.
      The obtained data are discussed in terms of the hypothesis of mechanical stress
      hyper-restoration.

PMID- 19405453
TI  - [There is often a light from out of the shadows].

PMID- 19405454
TI  - [Is the diagnostic-related group always at fault?].

PMID- 19405455
TI  - [Familiarity with every-day activities].

PMID- 19405456
TI  - ["The profession of the specialist is more closely allied with the patient"].

PMID- 19405457
TI  - [Concept for improving the processes of death].

PMID- 19405458
TI  - ["I chatter with advice to no-one about anything"].

PMID- 19405459
TI  - [Taking another risk, even when it can get hard].

PMID- 19405460
TI  - [An unhealthy development].

PMID- 19405461
TI  - [Responsibilities and stakes in one's life work].

PMID- 19405463
TI  - [When the signs are unlucky].

PMID- 19405462
TI  - [The patient with dementia, a completely separate subject].

PMID- 19405464
TI  - [Domestic violence].

PMID- 19405466
TI  - High-pressure (up to 10.7 GPa) crystal structure of single-component molecular
      metal [Au(tmdt)2].
AB  - The crystal structure of the single-component molecular metal [Au(tmdt)(2)] was
      examined at pressures up to 10.7 GPa in order to examine whether the high
      pressure structure reflects the crystal's metallic nature. Crystal structure
      analyses were performed at 0.2, 0.8, 1.3, 3.0, 5.5, and 10.7 GPa on the basis of
      the powder X-ray diffraction data obtained by using the synchrotron radiation
      source SPring-8. The unit cell volume at 10.7 GPa was approximately 75% of the
      initial volume, indicating that [Au(tmdt)(2)] is a 'soft material' like a typical
      molecular crystal in spite of its metallic nature. The pressure dependences of
      the bond lengths of the Au(tmdt)(2) molecule were found to be approximately 1
      order of magnitude smaller than those of the intermolecular atomic distances.
      These results seem to justify the commonly accepted conjecture that the molecule
      usually behaves almost like a rigid body up to a fairly high pressure. It was
      found that the anisotropy of the lattice compression of the insulating I(2)
      crystal below 20 GPa can be essentially interpreted on the basis of a very simple
      'interatomic repulsion model', which assumes that the molecules in the crystal
      are packed such that as far as possible, an increase in the interatomic
      repulsions between neighboring molecules is avoided. However, the maximum
      decrease in the intermolecular distance in [Au(tmdt)(2)] was observed along the a
      direction although there were many intermolecular S...S contacts shorter than the
      van der Waals distance (3.70 A) along this direction. The shortest intermolecular
      S...S distance was 2.73 A at 10.7 GPa, which is approximately 1 A shorter than
      the S...S van der Waals distance (3.70 A). The crystal lattice of [Au(tmdt)(2)]
      is considered to be stabilized by the enhancement of the intermolecular
      overlapping of the conduction molecular orbitals having large amplitudes on
      peripheral S atoms. Although the crystal is composed of 'isolated molecules' like
      a typical insulating molecular crystal, its compressibility behavior seems to
      reflect its metallic nature.

PMID- 19405467
TI  - Increased dispersion of supported gold during methanol carbonylation conditions.
AB  - The active site in supported gold catalysts for the carbonylation of methanol has
      been identified as dimers/trimers of gold which are formed from large gold
      particles >10 nm in diameter. Methyl iodide was found to be critical for this
      dispersion process and to maintain the catalyst in the active form. This study
      also shows that it may be possible to redisperse gold catalysts, in general,
      after reaction.

PMID- 19405465
TI  - Solution and fluorescence properties of symmetric dipicolylamine-containing
      dichlorofluorescein-based Zn2+ sensors.
AB  - The mechanism by which dipicolylamine (DPA) chelate-appended fluorophores respond
      to zinc was investigated by the synthesis and study of five new analogues of the
      2',7'-dichlorofluorescein-based Zn(2+) sensor Zinpyr-1 (ZP1). With the use of
      absorption and emission spectroscopy in combination with potentiometric
      titrations, a detailed molecular picture has emerged of the Zn(2+) and H(+)
      binding properties of the ZP1 family of sensors. The two separate N(3)O donor
      atom sets on ZP1 converge to form binding pockets in which all four heteroatoms
      participate in coordination to either Zn(2+) or protons. The position of the
      pyridyl group nitrogen atom, 2-pyridyl or 4-pyridyl, has a large impact on the
      fluorescence response of the dyes to protons despite relatively small changes in
      pK(a) values. The fluorescence quenching effects of such multifunctional electron
      donating units are often taken as a whole. Despite the structural complexity of
      ZP1, however, we provide evidence that the pyridyl arms of the DPA appendages
      participate in the quenching process, in addition to the contribution from the
      tertiary nitrogen amine atom. Potentiometric titrations reveal ZP1 dissociation
      constants (K(d)) for Zn(2+) of 0.04 pM and 1.2 nM for binding to the first and
      second binding pockets of the ligand, respectively, the second of which
      correlates with the value observed by fluorescence titration. This result
      demonstrates that both binding pockets of this symmetric, ditopic sensor need to
      be occupied in order for full fluorescence turn-on to be achieved. These results
      have significant implications for the design and implementation of fluorescent
      sensors for studies of mobile zinc ions in biology.

PMID- 19405468
TI  - TfNH2 as achiral hydrogen-bond donor additive to enhance the selectivity of a
      transition metal catalyzed reaction. Highly enantio- and diastereoselective
      rhodium-catalyzed cyclopropanation of alkenes using alpha-cyano diazoacetamide.
AB  - A highly stereoselective (up to 98% ee and 99:1 dr) Rh(II)-catalyzed formation of
      nitrile-substituted cyclopropanes is described. Alpha-cyano diazoacetamide
      reagents react with a variety of mono- and disubstituted olefins in good yields
      and excellent enantio- and diastereocontrol. Less reactive substrates, such as
      aliphatic olefins, also undergo the reaction. This new methodology features the
      unprecedented use of an achiral hydrogen-bond donor additive to enhance the
      selectivity and exploits the powerful trans-directing ability of amides solving
      the diastereocontrol issue of the formation of substituted 1-cyanocyclopropane-1
      carboxy derivatives.

PMID- 19405469
TI  - Photogelling colloidal dispersions based on light-activated assembly of
      nanoparticles.
AB  - Photorheological (PR) fluids, i.e., fluids whose rheology can be tuned by light,
      have been a recent focus for our laboratory. We are interested in low-cost
      approaches to PR fluids using molecules or materials that are readily available.
      Toward this end, we report a new concept for such fluids based on light-activated
      assembly of nanoparticles into a physical network (gel). Our system consists of
      disk-like nanoparticles of laponite along with a surfactant stabilizer (Pluronic
      F127) and the photoacid generator (PAG), diphenyliodonium-2-carboxylate
      monohydrate. Initially, the nanoparticles are sterically stabilized by the
      surfactant, and the result is a stable, low-viscosity dispersion. Upon UV
      irradiation, the PAG gets photolyzed, lowering the pH by approximately 3 units.
      In turn, the stabilizing surfactant is displaced from the negatively charged
      faces of the nanoparticle disks while the edges of the disks become positively
      charged. The particles are thereby induced to assemble into a three-dimensional
      "house-of-cards" network that extends through the sample volume. The net result
      is a light-induced sol to gel transition, i.e., from a low, water-like viscosity
      to an infinite viscosity and yield stress. The yield stress of the photogel is
      sufficiently high to support the weight of small objects. The gel can be
      converted back to a sol by increasing either the pH or the surfactant content.

PMID- 19405471
TI  - High hydrogen storage capacity of porous carbons prepared by using activated
      carbon.
AB  - A kind of activated carbon with further carbon dioxide and potassium hydroxide
      activations for hydrogen storage was investigated. The carbon dioxide and
      potassium hydroxide activations have apparently different effects on the pore
      structures and textures of the activated carbon which closely associated with the
      hydrogen storage properties. The potassium hydroxide activation can remarkably
      donate microporosity to the frameworks of the activated carbon. One of the
      resultant porous carbons exhibited a high surface area of up to 3190 m(2) g(-1)
      and large gravimetric hydrogen uptake capacity of 7.08 wt % at 77 K and 20 bar,
      which is one of the largest data reported for the porous carbon materials. This
      result suggests that the porous carbon with large amounts of active sites, high
      surface area, and high micropore volume related to optimum pore size could
      achieve high gravimetric hydrogen storage.

PMID- 19405470
TI  - A general solution for unstable boronic acids: slow-release cross-coupling from
      air-stable MIDA boronates.
AB  - Many boronic acids, including 2-heterocyclic, vinyl, and cyclopropyl derivatives,
      are inherently unstable, which can limit their benchtop storage and/or efficient
      cross-coupling. We herein report the first general solution to this problem: in
      situ slow release of unstable boronic acids from the corresponding air-stable
      MIDA boronates. This remarkably general approach has transformed all three
      classes of these unstable boronic acids into shelf-stable and highly effective
      building blocks for cross-coupling with a wide range of aryl and heteroaryl
      chlorides.

PMID- 19405473
TI  - Metastable supramolecular polymer nanoparticles via intramolecular collapse of
      single polymer chains.
AB  - We present an elegant approach for fabricating polymeric nanoparticles via the
      reversible noncovalent intramolecular cross-linking of single polymer chains. By
      protecting the well-studied 2-ureido-pyrimidinone moiety with an o-nitrobenzyl
      group, we have introduced a latent quadruple hydrogen bonding motif.
      Incorporating this group into linear poly(norbornenes) creates a class of
      supramolecular materials that can be readily dissolved and subsequently cross
      linked upon irradiation with UV light, eliminating the need for selective solvent
      techniques. This is a facile method for producing well-defined particles with
      narrow polydispersity as confirmed by atomic force microscopy. By virtue of the
      nature of the intramolecular cross-linking (supramolecular interactions of
      pendant groups), these metastable nanoparticles are akin to folded
      biomacromolecules, representing the first step in linking synthetic polymers and
      self-folded biopolymers.

PMID- 19405472
TI  - Enantiomerization dynamics and a catalytic dynamic resolution of N-trimethylallyl
      2-lithiopyrrolidine.
AB  - The barriers to enantiomerization of N-trimethylallyl-2-lithiopyrrolidine have
      been measured in the presence of sparteine,1, N,N'-diisopropylbispidine, 2, and
      diaminoalkoxide 3. We have additionally demonstrated a rare example of a
      catalytic dynamic resolution using either of two ligands, achieving enantiomer
      ratios of up to 93:7.

PMID- 19405476
TI  - Pattern size reduction effect via a "mix and match" sequential imprinting
      technique.
AB  - Nanoimprint lithography is traditionally thought of as a one-to-one pattern
      replication process, where the negative of the surface relief pattern from a mold
      is reproduced exactly onto a resist material. As such, each pattern design will
      require a mold to be fabricated with the pattern required. The mold used is
      typically fabricated by various lithographic processes, many of which are costly
      and time-consuming. In this work, we report the use of a "mix and match"
      sequential imprinting technique where line-space patterns of different gap sizes
      were achieved through the different combinations of feature size and relative
      alignments of the molds. More significantly, patterns with gap sizes smaller than
      the molds were obtained, resulting in a size reduction effect. A gap size
      reduction as high as 93% had been achieved in imprinted polystyrene and we have
      exploited the patterns as shadow masks used for the deposition of nanometer sized
      metal lines. The main advantage of this gap size reduction effect lies in the
      tunability of the process, which removes the need for the design and purchase of
      newer and more expensive imprinting molds.

PMID- 19405477
TI  - Strain-induced droplet retraction memory in a pickering emulsion.
AB  - We studied the deformation and relaxation of a water droplet covered with
      polystyrene latex particles (diameter ca. 200 nm) and embedded in an immiscible
      fluid after a large strain jump. We show that the presence of the solid particles
      at the droplet interface slows down the retraction kinetics in comparison with a
      pure water droplet and induces flow singularity not observed with pure water
      droplets. The terminal relaxation time of the retraction process, defined as the
      characteristic time required for the droplet to relax to its spherical
      equilibrium shape, increases linearly with the applied strain. This result
      implies a memory effect induced by the presence of solid particles at the droplet
      interface in a solid-stabilized or Pickering emulsion.

PMID- 19405474
TI  - Biochemical and biophysical analysis of five disease-associated human
      adenylosuccinate lyase mutants.
AB  - Adenylosuccinate lyase (ASL), a catalyst of key reactions in purine biosynthesis,
      is normally a homotetramer in which three subunits contribute to each of four
      active sites. Human ASL deficiency is an inherited metabolic disease associated
      with autism and mental retardation. We have characterized five disease-associated
      ASL mutants: R194C and K246E are located at subunit interfaces, L311V is in the
      central helical region away from the active site, and R396C and R396H are at the
      entrance to the active site. The V(max) (at 25 degrees C) for R194C is comparable
      to that of WT, while those of L311V, R396C, R396H, and K246E are considerably
      reduced and affinity for adenylosuccinate is retained. The mutant enzymes have
      decreased positive cooperativity as compared to WT. K246E exists mainly as dimer
      or monomer, accounting for its negligible activity, whereas the other mutant
      enzymes are similar to WT in the predominance of tetramer. At 37 degrees C, the
      specific activity of WT and these mutant enzymes slowly decreases 30-40% with
      time and reaches a limiting specific activity without changing significantly the
      amount of tetramer. Mutant R194C is unique in being rapidly inactivated at the
      harsher temperature of 60 degrees C, indicating that it is the least stable
      enzyme in vitro. Conformational changes in the mutant enzymes are evident from
      protein fluorescence intensity at 25 degrees C and after incubation at 37 degrees
      C, which correlates with the loss of enzymatic activity. Thus, these disease
      associated single mutations can yield enzyme with reduced activity either by
      affecting the active site or by perturbing the enzyme's structure and/or native
      conformation which are required for catalytic function.

PMID- 19405475
TI  - Nuclear receptors homo sapiens Rev-erbbeta and Drosophila melanogaster E75 are
      thiolate-ligated heme proteins which undergo redox-mediated ligand switching and
      bind CO and NO.
AB  - Nuclear receptors E75, which regulates development in Drosophila melanogaster,
      and Rev-erbbeta, which regulates circadian rhythm in humans, bind heme within
      their ligand binding domains (LBD). The heme-bound ligand binding domains of E75
      and Rev-erbbeta were studied using electronic absorption, MCD, resonance Raman,
      and EPR spectroscopies. Both proteins undergo redox-dependent ligand switching
      and CO- and NO-induced ligand displacement. In the Fe(III) oxidation state, the
      nuclear receptor hemes are low spin and 6-coordinate with cysteine(thiolate) as
      one of the two axial heme ligands. The sixth ligand is a neutral donor,
      presumably histidine. When the heme is reduced to the Fe(II) oxidation state, the
      cysteine(thiolate) is replaced by a different neutral donor ligand, whose
      identity is not known. CO binds to the Fe(II) heme in both E75(LBD) and Rev
      erbbeta(LBD) opposite a sixth neutral ligand, plausibly the same histidine that
      served as the sixth ligand in the Fe(III) state. NO binds to the heme of both
      proteins; however, the NO-heme is 5-coordinate in E75 and 6-coordinate in Rev
      erbbeta. These nuclear receptors exhibit coordination characteristics that are
      similar to other known redox and gas sensors, suggesting that E75 and Rev-erbbeta
      may function in heme-, redox-, or gas-regulated control of cellular function.

PMID- 19405478
TI  - Enzyme-activated RGD ligands on functionalized poly(ethylene glycol) monolayers:
      surface analysis and cellular response.
AB  - We report on the design, stepwise synthesis, and surface analysis of enzyme
      responsive surfaces that present cell adhesive RGD sequences on-demand, that is,
      by enzymatic hydrolysis of inactive RGD containing precursors that carry
      cleavable steric blocking groups. These surfaces, incorporating poly(ethylene
      glycol) (PEG) monolayers coupled via epoxy silanes to glass, are functionalized
      via stepwise solid phase synthesis, presenting a versatile and straightforward
      approach to preparation of peptide surfaces. Successive amino acid coupling and
      deprotection steps using fluorenylmethoxycarbonyl (Fmoc) chemistry are verified
      using surface analysis with time-of-flight secondary-ion mass spectrometry (ToF
      SIMS) and X-ray photoelectron spectroscopy (XPS). Exposure of surfaces to
      elastase results in activation of cell binding ligands as demonstrated using
      osteoblast cells. These surfaces may have applications in spatiotemporally
      controlled attachment of cells as relevant for three-dimensional tissue
      engineering scaffolds and cell-based biosensors.

PMID- 19405479
TI  - An innovative method to control the incipient flow boiling through grafted
      surfaces with chemical patterns.
AB  - The onset of flow boiling of a liquid is linked to the superheat condition that
      is necessary to activate the nucleation sites on contacting surfaces. The
      nucleation sites are usually represented by cavities in the rough surface of the
      heat exchanger. On smooth surfaces, the region where bubble detachment does not
      occur due to the lack of superheating may constitute a serious limitation for
      microfluidic devices. This paper shows the first experimental evidence that the
      position of the active nucleation sites can be controlled through chemical
      patterning of smooth surfaces: in this study, the heated surfaces are chemically
      grafted with alkylsilane self-assembled monolayers by microcontact printing. The
      analysis of the propagation of the bubble zone area quantitatively shows that the
      bubbles remain localized on top of the grafted zone and that, in the initial
      phase of the experiment, the center of mass of the bubble zone only moves along
      the vertical axis, without lateral drift.

PMID- 19405480
TI  - Engineering transfer of micro- and nanometer-scale features by surface energy
      modification.
AB  - Micropatterning of surfaces is gaining importance in various applications ranging
      from biosensors to microfluidic and lab-on-a-chip devices, where the control of
      the surface chemistry is of great importance for the application. In this paper,
      we introduce a patterning technique of topographical features, which is
      applicable on different substrates by modifying their surface energy. The
      textured surface is obtained via polydimethylsiloxane (PDMS) transfer, and the
      topographical parameters can be systematically tailored by selective treatment
      with oxygen plasma of either the PDMS stamp, the substrate, or both. Our approach
      is an alternative technique to create micro- and nanopatterns of various height
      and shape over a large area on different substrates. The possibility to control
      cell behavior on different surfaces tailored with this microtransfer patterning
      approach was also evaluated. The cell culture on patterned surfaces showed the
      possibility of modulating cell adhesion. Our method is based on simple transfer
      of silicone elastomeric patterns to the surface, and therefore, it is very simple
      and fast compared to other complex techniques. These observations could have
      implications for tissue-scaffold engineering science in areas such as
      microfluidic devices and control of cell adhesion.

PMID- 19405482
TI  - Micromachined hydrogel stamper for soft printing of biomolecules with adjustable
      feature dimensions.
AB  - We report on the development of a hydrogel stamper with built-in reservoirs for
      soft-printing of biomolecules with adjustable feature dimensions. The stamper
      consists of potassium hydroxide (KOH)-etched silicon cavities onto which
      biomolecule-soaked low cross-linked density hydrogel with large pores and low
      mechanical strength is loaded. Application of weight to the top surface allows
      for a controllable protrusion of hydrogel from the opposite nozzles. Such
      protrusion combined with a suitable spacer between the stamper and a substrate
      provides a means for printing features with dimensions depending on the applied
      weight. Utilizing the above method, we successfully stamped bovine serum albumin
      conjugated with fluorescein isothiocyanate (BSA-FITC) model proteins on
      hydrophilic silicon substrates with a feature dimension ratio of 20:1 using a
      single stamper.

PMID- 19405481
TI  - Asymmetric wetting of patterned surfaces composed of intrinsically hysteretic
      materials.
AB  - Wetting of chemically heterogeneous surfaces is modeled using a phase field
      theory. We focus on a chemically heterogeneous surface composed of squares of one
      component material embedded in another. Unlike previous studies where the
      component materials were characterized only by an equilibrium contact angle, in
      this paper each of the component materials is constitutively allowed to exhibit
      hysteresis. Using this approach, we investigate the effect of heterogeneity
      length scale on observed macroscopic behavior. Cassie theory is found to be
      applicable only in the limit of vanishing length scale. For surfaces with a
      finite heterogeneity length scale, the advancing and receding contact angles
      deviate from Cassie theory. We find that this deviation and its length scale
      dependence are asymmetric and depend on the wetting properties of the embedded
      material relative to the contiguous substrate.

PMID- 19405483
TI  - Theoretical insights into the hydrated (10.4) calcite surface: structure,
      energetics, and bonding relationships.
AB  - Roothaan-Hartree-Fock molecular orbital methods were applied to investigate the
      ground-state structural, energetic properties, and bonding relationships of the
      hydrated (10.4) calcite surface. The adsorption of water molecules was modeled at
      the 6-31G(d,p) level of theory using Ca(n)(CO(3))(n) slab cluster models (4 <or=
      n <or= 18) with a varying number of H(2)O monomers (2 <or= (H(2)O)(n) <or= 6)
      interacting with the surface. Modeling results add fresh insights into the
      detailed 3D structural registry of the first and second hydration layers and the
      reconstructed (10.4) calcite surface, complementary to the information acquired
      from earlier atomistic, density functional, X-ray scattering, and grazing
      incidence X-ray diffraction studies. Both the modeled energies and geometries
      agree best with results of earlier density functional calculations, supporting
      the associative character of adsorbed water molecules. Two adsorption
      configurations are postulated: (i) H(2)O molecules interacting with surface Ca
      through ionic bonding and by hydrogen bonding to a surface O with their dipole
      slightly oblique above the surface (1st hydration layer), and (ii) H(2)O
      molecules that hydrogen bond to surface O and to H(2)O molecules in the first
      hydration layer with their dipole nearly parallel to the surface (2nd hydration
      layer). These interactions are consistent with the "chemisorption" and
      "physisorption" of H(2)O on calcite surfaces, proposed on the basis of previous
      thermogravimetric and Fourier-transformed infrared studies. Most significant is
      the distortion of the surface Ca-O octahedra caused by the relaxation (and
      possibly rupture) of some Ca-O bonds upon hydration, weakening the topmost atomic
      layer. These findings are consistent with interpretations of X-ray photoelectron
      spectroscopy, density functional theory, and electrokinetic studies that suggest
      the preferential release of surface Ca atoms over surface CO(3) groups upon
      hydration of the cleavage surface. These insights will help to elucidate
      mechanisms of carbonate mineral dissolution, the rearrangement of surface layers,
      ion replacement, charge development, and solute transport through subsurface
      lattice layers.

PMID- 19405484
TI  - Tuning microstructures in organogels: gelation and spectroscopic properties of
      mono- and bis-cholesterol-linked diphenylbutadiene derivatives.
AB  - The gelation and photophysical properties of mono- and bis-cholesterol
      derivatives linked to diphenylbutadiene have been investigated. Scanning electron
      microscopy of xerogels of the monocholesterol derivatives indicated that these
      molecules self-assemble into 3D networks consisting of helically twisted fibers.
      In contrast, the morphology of xerogels of the bis-cholesterol derivatives
      indicated agglomerated spheres. In concentrated solutions (> 10(-4) M), the self
      assembled superstructure of the monocholesterol derivatives consists of helically
      twisted fibers whereas that of the bis-cholesterol derivatives indicated
      clustered spheres. An investigation of spectroscopic properties suggests that the
      morphology of the superstructures formed in these systems may be correlated to
      the nature of the molecular aggregates formed. Absorption and emission spectral
      studies as a function of concentration and temperature suggested the formation of
      predominantly J-type aggregates in the monocholesterol and H-type aggregates in
      the bis-cholesterol derivatives. It is proposed that the slipped stack
      arrangement within the J aggregates of the monocholesterol derivatives resulted
      in the formation of helically twisted fibers, whereas the cofacial arrangement in
      the H aggregates of the bis-cholesterol derivatives could prevent such fiber
      formation, resulting in the formation of the agglomerated spheres.

PMID- 19405485
TI  - Optoelectronic energy transfer at novel biohybrid interfaces using light
      harvesting complexes from Chloroflexus aurantiacus.
AB  - In nature, nanoscale supramolecular light harvesting complexes initiate the
      photosynthetic energy collection process at high quantum efficiencies. In this
      study, the distinctive antenna structure from Chloroflexus aurantiacusthe
      chlorosomeis assessed for potential exploitation in novel biohybrid
      optoelectronic devices. Electrochemical characterization of bacterial fragments
      containing intact chlorosomes with the photosynthetic apparatus show an increase
      in the charge storage density near the working electrode upon light stimulation
      and suggest that chlorosomes contribute approximately one-third of the overall
      photocurrent. Further, isolated chlorosomes (without additional photosynthetic
      components, e.g., reaction centers, biochemical mediators) produce a photocurrent
      (approximately 8-10 nA) under light saturation conditions. Correlative
      experiments indicate that the main chlorosome pigment, bacteriochlorophyll-c,
      contributes to the photocurrent via an oxidative mechanism. The results reported
      herein are the first to demonstrate that isolated chlorosomes (lipid-enclosed
      sacs of pigments) directly transduce light energy in an electrochemical manner,
      laying an alternative, biomimetic approach for designing photosensitized
      interfaces in biofuel cells and biomedical devices, such as bioenhanced retinal
      prosthetics.

PMID- 19405486
TI  - Scanning ion conductance microscopy: a model for experimentally realistic
      conditions and image interpretation.
AB  - Scanning ion conductance microscopy (SICM) is a scanned probe microscopy
      technique in which the probe is a fine glass pipet filled with a contact
      (reference) electrode and an electrolyte solution. The current flow between the
      reference electrode and a second reference electrode positioned in bulk solution
      when the two electrodes are biased externally can be used as a feedback signal to
      maintain a constant separation between the tip and a surface during imaging. In
      usual practice the tip position is modulated over a small amplitude perpendicular
      to the surface, and the resulting alternating current (AC) is used as the
      feedback signal, although the direct current can also be used. A comprehensive
      model for the current response is reported. Laplace's equation has been solved
      for the electrolyte solution for a range of tip geometries, enabling the factors
      controlling the tip current to be identified. The approach developed is shown to
      represent an improvement over earlier semiempirical treatments. To explore the
      influence of surface topography on the (AC) current response, various surfaces
      have been considered, including a tip moved toward a planar surface (in the
      normal direction) and tips scanned over a pit and a step in the surface. The
      results have allowed a critical assessment of the SICM response as a means of
      probing surface topography. Features identified through simulation have been
      found in experiments through studies of two model substrates for which imaging
      results are reported. In typical experimental practice, the response of the SICM
      tip to surface features occurs over much greater lateral distances than the size
      of the pipet aperture.

PMID- 19405487
TI  - Origin of solvent dependence of photosensitized splitting of a cyclobutane
      pyrimidine dimer by a covalently linked chromophore.
AB  - In model studies involving the mechanisms of DNA photolyases, two reverse solvent
      effects on the quantum yield of photosensitized splitting of a cyclobutane
      pyrimidine dimer (CPD) by a covalently linked chromophore have been reported. One
      is an increase in the splitting efficiency in lower polarity solvents for model
      compounds with a short linker between the dimer and the chromophore. Another is
      more efficient splitting in higher polarity solvents for model compounds with a
      flexible and long linker. To unravel mechanisms of two opposite solvent effects,
      five covalently linked indole-dimer compounds with different-length linkers were
      prepared. Two solvent effects as described above were observed through measuring
      quantum yields of dimer splitting of these model compounds in four solvents.
      According to Marcus theory, back electron transfer in the splitting reaction was
      analyzed quantitatively in light of relative data of a model compound in four
      solvents. It was demonstrated that the dependence of the quantum yield on solvent
      polarity for the flexible long-linker system would derive from the change in the
      distance between a dimer unit (acceptor) and an indole moiety (electron donor) in
      different solvents. With increasing solvent polarity, a U-shaped conformation of
      the model compound would become a preferred conformation because of the
      hydrophobic interaction between indole and dimer moiety, and their distances
      would become closer. On the basis of Marcus theory, calculated results reveal
      that the rate of back electron transfer would be slowed down with increasing
      solvent polarity and the distance reduced, giving a more efficient splitting.
      Meanwhile, some new insights into mechanisms of DNA photoreactivation mediated by
      photolyases were gained.

PMID- 19405488
TI  - Surface-initiated activators generated by electron transfer for atom transfer
      radical polymerization in detection of DNA point mutation.
AB  - Amplification-by-Polymerization reportedly offers a sensitive and detector-free
      approach for DNA detection. However, the requirement for an oxygen-free
      environment when classic radical polymerization reactions are used in signal
      amplification significantly limits the mobility of this approach for point-of
      need applications. We report here the employment of a purge-free
      controlled/"living" polymerization reaction, activators generated by electron
      transfer for atom transfer radical polymerization (AGET ATRP), to achieve signal
      amplification upon DNA hybridization. Its aptitude in simplifying assay procedure
      and shortening assay turn-around has been demonstrated in this report, which
      substantiates the feasibility of using Amplification-by-Polymerization for high
      throughput or portable screening of genetic mutations. In addition, employment of
      water-soluble ascorbic acid as the reducing agent has overcome the hurdles
      encountered by heterogeneous AGET ATRP reactions. Optimization of AGET ATRP in
      the presence of oligonucleotides has been conducted where tris[(2
      pyridyl)methyl]amine (TPMA) was selected as the catalyst ligand for its mild
      reaction rate. Effective polymer growth has been achieved when the concentration
      of the Cu(II) catalyst was controlled at 20 mM and ascorbic acid at 18 mM. The
      propagation and termination reaction constants have been derived, purporting the
      speculated controlled growth kinetics during polymer grafting. A linear
      relationship between the grafted polymer film thickness and the amount of
      captured DNA target sequences has been established, which provides the
      quantification basis during DNA detection. Detection of DNA sequences with single
      point mutations has been successful regardless of the mutation site.

PMID- 19405489
TI  - Fabrication and electrocatalytic properties of chitosan and keplerate-type
      polyoxometalate {Mo72Fe30} hybrid films.
AB  - Hybrid films composed of chitosan and Keplerate-type polyoxometalate, {Mo72Fe30}
      (Mo72VIFe30IIIO252L102.ca.180H2O, L=H2O/CH3COO-/Mo2O8/9n-), were fabricated on
      quartz, silicon, and ITO substrates by layer-by-layer (LbL) method. The LbL films
      were characterized by UV-vis spectroscopy, X-ray photoelectron spectroscopy
      (XPS), atomic force microscopy (AFM), and cyclic voltammetry (CV). UV-vis spectra
      show that the absorbance values at characteristic wavelengths of the multilayer
      films increase almost linearly with the number of chitosan/{Mo72Fe30} bilayers.
      XPS spectra confirm the incorporation of chitosan and {Mo72Fe30} into the films.
      The electrocatalytic reduction of ClO3-, BrO3-, and IO3- by chitosan/{Mo72Fe30}
      hybrid films in an acidic aqueous solution shows an electrocatalytic reduction
      activity of IO3->BrO3->ClO3-. In particular, the modified electrodes exhibited
      high electrocatalytic activity for reduction of IO3-.

PMID- 19405490
TI  - Note on the free energy of transfer of fullerene C60 simulated by using classical
      potentials.
AB  - Diverse atomistic parameters of C60 have been developed and utilized to simulate
      fullerene solutions in biological environments. However, no thermodynamic
      assessment and validation of these parameters have been so far realized. Here, we
      employ extensive molecular dynamics simulations with the thermodynamic
      integration method in the isothermal-isobaric ensemble to investigate the
      transfer of a single fullerene C60 between different solvent environments using
      different potential models. A detailed analysis is performed on the structure and
      standard Gibbs free energy of transfer of C60 from benzene to ethanol. All of the
      interactions concerned in the transfer process are included via atomistic models.
      We notice that having only structural and dynamical properties is not decisive to
      validate reliable atomic parameters capable of describing a more realistic
      thermodynamic process. Thus, we employ the calculated free energy of transfer to
      validate more accurate atomic parameters for the solvation thermodynamics of
      fullerenes by direct comparison with the solubility experimental data.

PMID- 19405491
TI  - Nickelacyclic-cobaltocene vs. nickelacyclic-nickelocene. Synthesis, X-ray
      structures, electron transfer activity, EPR spectroscopy, and theoretical
      calculations.
AB  - Reactions of 9-nickelafluorenyllithium with cobalt and nickel
      pentamethylcyclopentadienyl-acetylacetonates resulted in the formation of the
      novel nickelacyclic-cobaltocene 2 and nickelacyclic-nickelocene 3, respectively,
      in which the central metal atom is bonded to the nickelafluorenyl ring. On the
      basis of their redox propensity, compounds 2 and 3 were oxidized to the
      corresponding monocations [2](+) and [3](+). The crystal and molecular structures
      of both the redox couples were determined by single-crystal X-ray analysis. In
      spite of their structural similarity, they display a rather different electron
      transfer ability. To throw light on such an aspect, the pertinent redox couples
      have been examined by EPR spectroscopy and the nature of the frontier orbitals
      involved in the redox activity of the neutral precursors has been supported by
      extended Huckel theoretical calculations.

PMID- 19405492
TI  - Solid-phase synthesis of novel 7,8-functionalized pyrazolo[1,5-a][1,3,5]-2-oxo-4
      thioxotriazine derivatives via cyclization reactions of dithiocarboxy resin bound
      pyrazoles.
AB  - A general method is described for the solid-phase synthesis of novel 7,8
      functionalized pyrazolo[1,5-a][1,3,5]-2-oxo-4-thioxotriazine derivatives. The
      sequence developed for this purpose is based on cyclization reactions of resin
      bound 3,4-functionalized-5-amino-1-dithiocarboxypyrazoles 4 and 5, promoted by
      reaction with various isocyanates. The resin-bound pyrazoles produced by
      cyclization reactions of cyanocarboimidates 8 or 3-ethoxyacrylonitriles 9 with
      Merrifield resin linked hydrazine dithiocarbazate 3, serve as key intermediates
      for subsequent bicyclic heterocycle diversification. Reactions of the resin-bound
      5-amino-1-dithiocarboxy pyrazoles 4 and 5 with various aryl isocyanates produce
      the novel 7,8-functionalized pyrazolo[1,5-a][1,3,5]-2-oxo-4-thioxotriazine
      derivatives 6 and 7 in good yields and high purities.

PMID- 19405493
TI  - Spectroscopic study of the benchmark Mn+-H2 complex.
AB  - We have recorded the rotationally resolved infrared spectrum of the weakly bound
      Mn+-H2 complex in the H-H stretch region (4022-4078 cm(-1)) by monitoring Mn+
      photodissociation products. The band center of Mn+-H2, the H-H stretch
      transition, is shifted by -111.8 cm(-1) from the transition of the free H2
      molecule. The spectroscopic data suggest that the Mn+-H2 complex consists of a
      slightly perturbed H2 molecule attached to the Mn+ ion in a T-shaped
      configuration with a vibrationally averaged intermolecular separation of 2.73 A.
      Together with the measured Mn+...H2 binding energy of 7.9 kJ/mol (Weis, P.; et
      al. J. Phys. Chem. A 1997, 101, 2809.), the spectroscopic parameters establish
      Mn+-H2 as the most thoroughly characterized transition-metal cation-dihydrogen
      complex and a benchmark for calibrating quantum chemical calculations on
      noncovalent systems involving open d-shell configurations. Such systems are of
      possible importance for hydrogen storage applications.

PMID- 19405494
TI  - Unusual hydrophobic interactions in acidic aqueous solutions.
AB  - Hydrophobic interaction, which is believed to be a primary driving force for many
      fundamental chemical and biological processes such as nanostructure self
      assembly, micelle formation, and protein folding, is different in acidic aqueous
      solutions compared to salt solutions. In this study, the aggregation/dispersion
      behavior of nonpolar hydrophobic molecules in aqueous solutions with varying acid
      (HCl) concentrations is investigated using novel molecular dynamics simulations
      and compared to the hydrophobic behavior in corresponding salt (NaCl) solutions.
      The formation of unusual weakly bound hydrophobe-hydrated proton solvation
      structures is observed and can be attributed to the unique "amphiphilic"
      characteristic of hydrated protons. This molecular-level mechanism for the acid
      enhanced dissolution of hydrophobic particles also provides a novel
      interpretation for the apparent anomaly of the hydronium cation in the Hofmeister
      series.

PMID- 19405495
TI  - The unusual solid-state structure of mercury oxide: relativistic density
      functional calculations for the group 12 oxides ZnO, CdO, and HgO.
AB  - The solid-state structure of mercury oxide and its low-pressure modifications are
      known to significantly differ from those found for the corresponding zinc and
      cadmium compounds, that is, one changes from a simple hexagonal wurtzite or cubic
      rock salt structure found in zinc oxide and cadmium oxide to unusual chainlike
      montroydite and cinnabar structures in mercury oxide. Here, we present
      relativistic and nonrelativistic density functional studies which demonstrate
      that this marked structural difference is caused by relativistic effects. For
      HgO, the simple rock salt structure is only accessible at higher pressures.
      Relativistic effects reduce the cohesive energy by 2.2 eV per HgO unit and
      decrease the density of the crystal by 14% due to a change in the crystal
      symmetry. Band structure and density of states calculations also reveal large
      changes in the electronic structure due to relativistic effects, and we argue
      that the unusual yellow to red color of HgO is a relativistic effect as well.

PMID- 19405496
TI  - Molecular modeling of imidazolium-based [Tf2N-] ionic liquids: microscopic
      structure, thermodynamic and dynamic properties, and segmental dynamics.
AB  - The microscopic structure, thermodynamic properties, local segmental dynamics,
      and self-diffusion coefficients of three ionic liquids (ILs) with a common anion,
      namely, the bis(trifluoromethylsulfonyl) imide ([Tf2N-]), and imidazolium-based
      cations that differ in the alkyl tail length, namely, the 1-butyl-3
      methylimidazolium ([C4mim+]), the 1-hexyl-3-methylimidazolium ([C6mim+]), and the
      1-octyl-3-methylimidazolium ([C8mim+]), are calculated over the temperature range
      of 298.15-333.15 K and pressure range of 0.1-60 MPa. Quantum calculations based
      on density functional theory are performed on isolated ion pairs, and minimum
      energy conformers are identified. Electronic density results are used to estimate
      the electrostatic potential of a molecular force field that is used subsequently
      for long molecular dynamics (MD) simulations of bulk ILs. Thermodynamic
      properties calculated from MD are shown to be in excellent agreement for the bulk
      density and good agreement for derivative properties when compared to
      experimental data. The new force field is an improvement over earlier ones for
      the same ILs. The microscopic structure as expressed through the radial
      distribution function is thoroughly calculated, and it is shown that the bulk
      structure characteristics are very similar to those obtained from the quantum
      calculations on isolated ion pairs. The segmental dynamics expressed in terms of
      bond and torsion angle decorrelation is shown to assume a broad range of
      characteristic times. Molecular segments in the alkyl tail of the cations are
      significantly faster than segments in the vicinity of the imidazolium ring.
      Finally, the new force field predicts accurately the self-diffusion coefficients
      of the cations and the anions over the entire temperature range examined, thus
      confirming its validity for a broad range of physical properties.

PMID- 19405497
TI  - OH-initiated degradation of unsaturated esters in the atmosphere: kinetics in the
      temperature range of 287-313 K.
AB  - The kinetics of the gas-phase reactions of hydroxyl radicals (OH) with methyl
      methacrylate (k(1)), butyl methacrylate (k(2)), butyl acrylate (k(3)), and vinyl
      acetate (k(4)) have been investigated for the first time as a function of
      temperature using the relative technique. The experiments were performed in a
      1080 L quartz glass photoreactor over the temperature range (T = 287-313 K) at a
      total pressure of 760 +/- 10 Torr synthetic air using in situ FTIR absorption
      spectroscopy to monitor the concentration-time behaviors of reactants. OH
      radicals were produced by the 254 nm photolysis of hydrogen peroxide (H(2)O(2)).
      The following Arrhenius expressions (in units of cm(3) molecule(-1) s(-1))
      adequately describe the measured rate coefficients as a function of temperature:
      k(1) = (1.97 +/- 0.95) x 10(-12) exp[(921 +/- 52)/T], k(2) = (1.65 +/- 1.05) x
      10(-11) exp[(413 +/- 34)/T], k(3) = (4.4 +/- 2.5) x 10(-13) exp[(1117 +/-
      105)/T], and k(4) = (4.06 +/- 2.02) x 10(-12) exp[(540 +/- 49)/T]. All of the
      rate coefficients display a negative temperature dependence and low pre
      exponential factor, which supports an addition mechanism for the reactions
      involving reversible OH-adduct formation. The rate coefficients (in units of
      cm(3) molecule(-1) s(-1)) determined at room temperature (298 K) were as follows:
      k(1) = (4.30 +/- 0.98) x 10(-11), k(2) = (6.63 +/- 1.42) x 10(-11), k(3) = (2.17
      +/- 0.48) x 10(-11), and k(4) = (2.48 +/- 0.61) x 10(-11). The results are
      compared with previous values of the rate coefficients reported in the
      literature, which were mainly measured at room temperature. The reactivity of the
      various unsaturated esters toward the OH radical is discussed in terms of
      structure activity relationships and parallels are drawn with the OH-radical
      activities of structurally similar compounds. Using the kinetic parameters
      determined in this work, residence times of the esters in the atmosphere with
      respect to their reaction with OH have been determined and are compared with
      other possible degradation pathways. Possible atmospheric implications of the
      various degradation pathways studied are discussed.

PMID- 19405498
TI  - Rotationally inelastic collisions of CN(A(2)Pi) with small molecules.
AB  - An optical-optical double resonance technique has been utilized to investigate
      rotational energy transfer of selected rotational/fine-structure levels of
      CN(A(2)Pi, v = 3) in collisions with the molecular partners CO(2) and CH(4).
      Total removal rate constants for several rotational/fine-structure levels were
      measured for both collision partners. State-to-state relative rate constants were
      determined for several initial levels. These show a strikingly strong collisional
      propensity to conserve the fine-structure/Lambda-doublet label, akin to our
      previous observations with the N(2) collision partner. The possible origin of
      this propensity is discussed.

PMID- 19405499
TI  - Combustion pathways of the alkylated heteroaromatics: bond dissociation
      enthalpies and alkyl group fragmentations.
AB  - The bond dissociation enthalpies (BDEs) of the alkyl groups of the alkyl
      substituted heterocycles have been studied and compiled using DFT methodology,
      with the intent of modeling the larger heterocyclic functionalities found in
      coal. DFT results were calibrated against CBS-QB3 calculations, and qualitative
      trends were reproduced between these methods. Loss of hydrogen at the benzylic
      position provided the most favorable route to radical formation, for both the
      azabenzenes and five-membered heterocycles. The ethyl derivatives had lower BDE
      values than the methyl derivatives due to increased stabilization of the
      corresponding radicals. Calculated spin densities correlated well with bond
      dissociation enthalpies for these compounds, while geometric effects were minimal
      with respect to the heterocycles themselves. Temperature effects on the bond
      dissociation enthalpies were minor, ranging by about 5 kcal/mol from 298 to 2000
      K; the free energies of reaction dropped significantly over the same range due to
      entropic effects. Monocyclic heteroaromatic rings were seen to replicate the
      chemistry of multicyclic heteroaromatic systems.

PMID- 19405500
TI  - New prototype isoreticular metal-organic framework Zn(4)O(FMA)(3) for gas
      storage.
AB  - A new isoreticular metal-organic framework Zn(4)O(FMA)(3).xG (1; FMA = fumarate;
      G = guest molecules) of a primitive cubic net was synthesized and structurally
      characterized. With intersecting pores of about 6.8 x 6.8 A, the activated 1a
      exhibits high gas adsorption with respect to H(2), CH(4), and CO(2).

PMID- 19405501
TI  - Accelerated development procedure for molecularly imprinted polymers using
      membrane filterplates.
AB  - A novel technique for the synthesis and testing of large numbers of molecularly
      imprinted polymers is described requiring much less time than the commonly used
      miniMIP approach. Instead of vials, the polymers are synthesized on the surface
      of microfiltration membranes in multiwell filterplates. The thin polymeric films
      enable accelerated template removal. The MIP development procedure is thereby
      shortened to two days. Performance of the system was demonstrated by creating a
      combinatorial library of MIPs selective for cimetidine, an antiulcer drug. The
      polymer composition has been optimized. An experimental design combined with a
      multivariate analysis (i.e., response surface modeling) was used to minimize the
      number of experiments in the optimization process. The highest imprinting factor
      was obtained using a MAA/EDMA/template molar ratio of 3.5:19.5:1.

PMID- 19405502
TI  - Electron super-rich radicals. III. On the peculiar behavior of the
      aminodihydroxymethyl radical in the gas phase.
AB  - In contrast to previously reported electron-super-rich trihydroxy-, triamino- and
      diaminohydroxymethyl radicals, the title aminodihydroxymethyl radical (1)
      generates a fraction of metastable species in the form of their deuterium
      isotopologues. The lifetimes of metastable radicals produced by femtosecond
      collisional electron transfer to aminodihydroxymethyl cations exceed 4 mus. The
      main fraction of 1 dissociates by fast loss of a hydroxyl hydrogen atom to form
      carbamic acid. Loss of an amino hydrogen atom is less facile and becomes <10%
      competitive at high internal energies or if the main dissociation is slowed down
      by deuterium isotope effects. RRKM calculations of unimolecular rate constants on
      a CCSD(T)/aug-cc-pVTZ potential energy surface gave a reasonably good fit for the
      competitive dissociations of 1 but not for the fraction of nondissociating
      radicals. The metastable species are attributed to excited electronic states
      which are predicted to have favorable Franck-Condon factors for being formed by
      collisional electron transfer.

PMID- 19405503
TI  - Synthesis of [60]fulleroindolines: palladium-catalyzed heteroannulations of
      [60]fullerene with o-iodoanilines.
AB  - The palladium-catalyzed reaction of C(60) with a variety of o-iodoanilines
      afforded the first synthesis of C(60)-fused indoline derivatives. A plausible
      reaction mechanism was proposed.

PMID- 19405504
TI  - Ring-closing metathesis reactions on azinium salts: straightforward access to
      quinolizinium cations and their dihydro derivatives.
AB  - The ring-closing metathesis reaction of 1-butenyl-2-vinylpyridinium salts and 2
      butenyl-1-vinylpyridinium salts using Grubbs second generation and Hoveyda-Grubbs
      catalysts proved to be an efficient approach to 3,4-dihydro- and 1,2
      dihydroquinolizinium salts and the corresponding quinolizinium derivatives by an
      improved thermal oxidation in the presence of Pd/C without solvent. A comparative
      study showed that the quinolizinium system was obtained in better yields through
      the 3,4-dihydroquinolizinium route, thus allowing the synthesis of quinolizinium
      derivatives or improvements in the yields of some examples reported previously.

PMID- 19405505
TI  - Why is the Suzuki-Miyaura cross-coupling of sp3 carbons in alpha-bromo sulfoxide
      systems fast and stereoselective? A DFT study on the mechanism.
AB  - The stereoselectivity-determining oxidative addition step in the Suzuki-Miyaura
      cross-coupling of alpha-bromo sulfoxides is analyzed computationally through DFT
      calculations on a model system defined by Pd(PMe(3))(2) and CH(3)SOCH(2)Br. Both
      monophospine and bisphosphine complexes have been considered, different reaction
      pathways being characterized through location of the corresponding transition
      states. The lowest energy transition states correspond to nucleophilic
      substitution mechanisms, which imply inversion of configuration at the carbon, in
      good agreement with experimental data on the process. The energy-lowering and
      stereodirecting role of the sulfinyl substituent is explained through its
      attractive interactions with the palladium center, which are only possible in the
      most favored mechanisms.

PMID- 19405506
TI  - Crystal structure of a trypanocidal 4,4'-bis(imidazolinylamino)diphenylamine
      bound to DNA.
AB  - The pursuit of small molecules that bind to DNA has led to the discovery of
      selective and potent antitrypanosomal agents, specifically 4,4'
      bis(imidazolinylamino)- and 4,4'-bis(guanidino)diphenylamine compounds, CD27 and
      CD25, respectively. Although the antitrypanosomal properties of these compounds
      have been characterized, further development of this series of compounds requires
      assessment of their DNA site selectivities and affinities. Toward this end, both
      compounds have been analyzed and found to selectively bind AT sequences. However,
      CD27 was found to bind with higher affinity to 5'-AATT than 5'-ATAT while CD25
      bound more weakly but equally well to either sequence. To detail the nature of
      its interactions with DNA, the crystal structure of CD27, bound to its preferred
      DNA-binding site 5'-AATT within a self-complementary oligonucleotide, 5'
      d(CTTAATTCGAATTAAG), was determined at 1.75 A using a host-guest approach.
      Although CD27 is predicted to be highly twisted in its energy-minimized state, it
      adopts a more planar crescent shape when bound in the minor groove of the DNA.
      Interactions of CD27 with 5'-AATT include bifurcated hydrogen bonds, providing a
      basis for selectivity of this site, and favorable van der Waals interactions in a
      slightly widened minor groove. Thus, an induced fit results from conformational
      changes in both the ligand and the DNA. Our studies suggest a basis for
      understanding the mechanism of the antitrypanosomal activity of these symmetric
      diphenylamine compounds.

PMID- 19405507
TI  - Concise synthesis of capuramycin.
AB  - A concise total synthesis of capuramycin (1), a promising preclinical TB drug
      lead, is achieved by high-yield formations of the cyanohydrin 5a and 4'',5''
      glycal derivative 12. Capuramycin can be synthesized in eight steps from the
      uridine building block 5a with >30% overall yield. The synthetic intermediates
      reported here are useful for generation of analogs to improve pharmacokinetic
      properties of capuramycin.

PMID- 19405508
TI  - Cytotoxic and HIF-1alpha inhibitory compounds from Crossosoma bigelovii.
AB  - Cytotoxicity-guided fractionation of an organic solvent extract of the plant
      Crossosoma bigelovii led to the discovery of a new strophanthidin glycoside (1)
      and two new 2-methylchromone glycosides (2 and 3). Also isolated were the known
      chromones eugenin and noreugenin, the indole alkaloid ajmalicine, the
      dibenzylbutane lignan secoisolariciresinol, the dibenzylbutyrolactone lignan
      matairesinol, and the furanone 5-tetradec-5-enyldihydrofuran-2-one. Further
      investigation into the biological properties of strophanthidin glycosides
      revealed a connection between inhibition of HIF-1 activation and the
      glycosylation of the genin. This work is the first published study of the
      bioactive phytochemicals of the family Crossosomataceae.

PMID- 19405509
TI  - Biomolecular-motor-based nano- or microscale particle translocations on DNA
      microarrays.
AB  - We aimed to create autonomous on-chip systems that perform targeted
      translocations of nano- or microscale particles in parallel using machinery that
      mimics biological systems. By exploiting biomolecular-motor-based motility and
      DNA hybridization, we demonstrate that single-stranded DNA-labeled microtubules
      gliding on kinesin-coated surfaces acted as cargo translocators and that single
      stranded DNA-labeled cargoes were loaded/unloaded onto/from gliding microtubules
      at micropatterned loading/unloading sites specified by DNA base sequences. Our
      results will help to create autonomous molecular sorters and sensors.

PMID- 19405510
TI  - Copper-free "click" modification of DNA via nitrile oxide-norbornene 1,3-dipolar
      cycloaddition.
AB  - Nitrile oxides react smoothly and rapidly with norbornene-modified DNA in a
      copper-free click reaction. The reaction allows high density functionalization of
      oligodeoxyribonucleotides (ODNs) with a large variety of molecules directly on
      solid supports and even in synthesizers without the need for an additional
      catalyst.

PMID- 19405511
TI  - Enhanced electrocatalytic activity of Pt subnanoclusters on graphene nanosheet
      surface.
AB  - Graphene nanosheet (GNS) gives rise to an extraordinary modification to the
      properties of Pt cluster electrocatalysts supported on it. The Pt/GNS
      electrocatalyst revealed an unusually high activity for methanol oxidation
      reaction compared to Pt/carbon black catalyst. The Pt/GNS electrocatalyst also
      revealed quite a different characteristic for CO oxidation among the measured
      catalyst samples. It is found that Pt particles below 0.5 nm in size are formed
      on GNS, which would acquire the specific electronic structures of Pt, modifying
      its catalytic activities.

PMID- 19405512
TI  - Organocatalytic syn-aldol reactions of dioxanones with (S)-isoserinal hydrate:
      synthesis of L-deoxymannojirimycin and L-deoxyidonojirimycin.
AB  - We report a new protocol for synthesis of L-1-deoxymannojirimycin, L-1
      deoxyidonojirimycin, and the N-isopropyl derivative of the latter compound from
      the readily available precursors (S)-isoserinal hydrate and 2-tert-butyl-2-methyl
      1,3-dioxan-5-one. The key steps include diastereoselective proline-catalyzed syn
      aldol transformation and a reductive amination/cyclization.

PMID- 19405513
TI  - Alkyl derivatives of bis(perfluoroalkylsulfonylimino)trifluoromethanesulfonic
      acid.
AB  - N-methyl and N-ethyl derivatives of N-(trifluoromethylsulfonyl)-[N'
      (trifluoromethylsufonyl)-trifluoromethylsulfoximidoyl] imides 2a,b were prepared
      by alkylation of bis(trifluoromethylsulfonylimino)trifluoromethanesulfonic acid 1
      or its silver salt 1a. It turns out that these imides are strong alkylating
      agents in spite of the fact that Me (Et) groups are attached to nitrogen atom.
      The alkylating activity of n-PrI, i-PrI, n-BuI, and n-AmI in the presence of
      silver salt of bis(trifluoromethylsulfonylimino)trifluoromethanesulfonic acid 1a
      was investigated.

PMID- 19405514
TI  - Nuclear magnetic resonance studies on covalent modification of amino acids thiol
      and amino residues by monofunctional aryl 13C-isocyanates, models of skin and
      respiratory sensitizers: transformation of thiocarbamates into urea adducts.
AB  - Exposure to aryl isocyanates, intermediates in the manufacture of polyurethanes,
      provokes lung sensitization and asthma but also occupational allergic contact
      dermatitis, sensitization occurring from a single accidental exposure. The
      initial step in the sensitization process is believed to be the covalent binding
      of the -N triple bond C triple bond O group with nucleophilic residues on
      proteins. While a wide knowledge exists on the reactivity of skin sensitizers
      toward amino acids, little is known about respiratory sensitizers such as aryl
      isocyanates. (13)C-Labeled monofunctional aryl isocyanates were synthesized, and
      their reactivities toward nucleophilic amino acids, GSH, and a model peptide were
      studied by (13)C and [(1)H-(13)C] NMR spectroscopy. An acetonitrile/buffer
      solution was used as a solvent to avoid the hampering of the follow up of the
      reactivity by the isocyanate hydrolysis competing reaction. The compounds reacted
      with thiol groups, through the formation of thiocarbamate bonds and with amino
      groups to form urea derivatives. The reactivity was confirmed with GSH,
      containing both free amino and thiol groups, and with a model peptide,
      particularly in the case of the reaction with lysine. The use of (13)C NMR to
      follow the aryl isocyanates reversible conjugation with thiol groups is also
      reported. Particularly, it is shown that thiocarbamate adducts can be converted
      into adducts of the urea kind by reaction with amino groups. These results
      confirmed the hypothesis by which thiol-containing peptides/proteins may act as
      carriers of isocyanates for possible reaction at a later time and/or place with
      other nucleophiles and confirmed the role of lysine as a good competing
      nucleophilic amino acid. The reactivity of aryl isocyanates with thiol and amino
      groups needs thus to be considered in their assigned sensitization processes.

PMID- 19405515
TI  - Quantitation of pyridyloxobutyl DNA adducts in nasal and oral mucosa of rats
      treated chronically with enantiomers of N'-nitrosonornicotine.
AB  - N'-Nitrosonornicotine (NNN) is one of the most important strong carcinogens in
      tobacco products and is believed to play a significant role in the induction of
      esophageal cancer in smokers and oral cavity cancer in snuff dippers. NNN is
      metabolically activated through cytochrome P450-catalyzed alpha-hydroxylation. 2'
      Hydroxylation produces a reactive intermediate 4-(3-pyridyl)-4
      oxobutanediazohydroxide (7), which alkylates DNA to form pyridyloxobutyl (POB)
      DNA adducts. DNA pyridyloxobutylation from NNN treatment, as measured by released
      4-hydroxy-1-(3-pyridyl)-1-butanone (HPB, 8), has been observed in vitro and in
      vivo. In the present study, we have used liquid chromatography-electrospray
      ionization-tandem mass spectrometry (LC-ESI-MS/MS) to analyze specific POB-DNA
      adducts in the nasal olfactory, nasal respiratory, and oral mucosa of F344 rats
      treated chronically with (R)-NNN or (S)-NNN in the drinking water (10 ppm, 1-20
      weeks). Adduct levels in the nasal respiratory mucosa exceeded those in the nasal
      olfactory and oral mucosa. (R)-NNN treatment generated 2-4 times more adducts in
      the nasal olfactory and respiratory mucosa than did (S)-NNN at most time points.
      O(2)-[4-(3-Pyridyl)-4-oxobut-1-yl]thymidine (O(2)-POB-dThd, 11) predominated in
      the nasal olfactory and respiratory mucosa, followed by 7-[4-(3-pyridyl)-4-oxobut
      1-yl]guanine (7-POB-Gua, 14). Levels of O(2)-[4-(3-pyridyl)-4-oxobut-1
      yl]cytosine (O(2)-POB-Cyt, 13) and O(6)-[4-(3-pyridyl)-4-oxobut-1-yl]-2'
      deoxyguanosine (O(6)-POB-dGuo, 12) were significantly lower. In the oral mucosa,
      the opposite stereoselectivity was observed, with (S)-NNN treatment producing 3-5
      times more POB-DNA adducts than did (R)-NNN. O(2)-POB-dThd and 7-POB-dGuo were
      the two major adducts, and their levels were similar. Overall, POB-DNA adduct
      formation in the nasal olfactory and nasal respiratory mucosa was similar to that
      previously observed in the lung, whereas in the oral mucosa, the trend resembled
      that in the esophagus. These results indicate that different mechanisms are
      involved in NNN metabolism and tumorigenesis in rat nasal and oral tissues. NNN
      enters the nasal mucosa through the circulation, and tissue-specific metabolism
      is important, while in the oral mucosa, direct exposure and local activation both
      play significant roles. Our results also support the potential importance of NNN
      as an oral carcinogen in people who use smokeless tobacco products.

PMID- 19405517
TI  - Preparation of polymer monoliths that exhibit size exclusion properties for
      proteins and peptides.
AB  - Protein-resistant poly(ethylene glycol methyl ether acrylate-co-polyethylene
      glycol diacrylate) monoliths were prepared in 150 microm i.d. capillaries using
      novel binary porogenic solvents consisting of ethyl ether and poly(ethylene
      oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) or PPO-PEO-PPO
      copolymer with molecular weights (MWs) from 2700 to 5800. The effects of the MWs
      and concentrations of these surfactants in the porogenic solvent mixture on the
      pore properties of the resultant monoliths were investigated. Several of the
      monoliths showed improvements in protein and peptide separations over an extended
      MW range compared to monoliths synthesized using non-surfactant porogens (i.e.,
      low MW organic liquids). The pore size distributions were examined using inverse
      size-exclusion chromatography (ISEC) of a select series of proteins and peptides
      covering a wide MW range. It was found that the best monolith had relatively
      large fractions of micropores (<2 nm, 11.9%) and mesopores in the range from 2.8
      to 15.7 nm (8.5%), which are important for size-exclusion separation of peptides
      and proteins, respectively. The new monoliths possessed high mechanical rigidity
      that enabled them to withstand pressures up to approximately 4000 psi.

PMID- 19405516
TI  - The loop connecting metal-binding domains 3 and 4 of ATP7B is a target of a
      kinase-mediated phosphorylation.
AB  - Cu-ATPase ATP7B (Wilson's disease protein) transports copper into the trans-Golgi
      network for biosynthetic incorporation into ceruloplasmin and sequesters excess
      copper to endocytic vesicles for further export out of the cell. The activity and
      intracellular location of ATP7B are regulated by copper levels; the trafficking
      of ATP7B between cellular compartments is coupled to changes in the level of
      protein phosphorylation. Neither the nature of the kinase(s) phosphorylating
      ATP7B nor the location of phosphorylation sites is known. We demonstrate that the
      membrane-bound ATP7B is phosphorylated by an ATP-dependent, GTP-independent
      kinase that can be either soluble or membrane-associated. Mg(2+) or Mn(2+) is
      necessary for kinase activity. We further show that the recombinant N-terminal
      domain of ATP7B (N-ATP7B) is a specific target for a kinase-mediated
      phosphorylation in vitro and in cells. Although exogenous addition of copper is
      not required for kinase activity, copper binding to N-ATP7B markedly alters the
      exposure of loops connecting the metal-binding subdomains (MBDs) to proteolysis
      and facilitates phosphorylation by 25-30%. MBD1-2 and MBD4-5 linkers become
      protected, while MBD2-3 and MBD3-4 regions remain exposed. A significant, 5-fold
      increase in the level of phosphorylation is also observed for the ATP7B variant
      that lacks the 29 kDa N-terminal fragment (mostly likely comprised of MBD1-3).
      Analysis of phosphorylated peptides by two-dimensional gel electrophoresis and
      mass spectrometry points to the loop connecting MBD3 and MBD4 as a region of
      phosphorylation. Altogether, the results suggest a mechanism in which kinase
      mediated phosphorylation of ATP7B is controlled by a conformational state of N
      ATP7B.

PMID- 19405518
TI  - Stabilized mixed micelles with a temperature-responsive core and a functional
      shell.
AB  - Formation and stabilization of multiresponsive micelles with a mixed
      poly(ethylene oxide)/polyelectrolyte shell and a temperature-responsive
      poly(propylene oxide) core were studied. Various poly(ethylene oxide)-block
      poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO) triblock
      copolymers were mixed with poly(acrylic acid)-block-poly(propylene oxide)-block
      poly(acrylic acid) (PAA-PPO-PAA) or poly(dimethylaminoethyl methacrylate)-block
      poly(propylene oxide)-block-poly(dimethylaminoethyl methacrylate) (PDMAEMA-PPO
      PDMAEMA) triblock copolymers. The micelles formed by binary mixtures of well
      defined compositions at a specific pH were additionally stabilized by loading
      with pentaerythritol tetraacrylate (PETA), that was polymerized and cross-linked
      "in situ" with UV assistance. Depending on both the composition of the copolymers
      and the experimental conditions, either spherical or wormlike "stabilized
      polymeric micelles with a mixed shell" (SPMMS) were observed by dynamic light
      scattering (DLS) and transmission electron microscopy (TEM). The SPMMS that
      contained PAA blocks in the shell were pH-sensitive, such that a reversible
      transition from well-dispersed SPMMS to precipitate could be promoted. In
      contrast, the SPMMS with a PEO/PDMAEMA mixed shell remained well-dispersed in the
      2-11 pH range. Finally, SPMMS were successfully exploited as templates for the
      preparation of Ag nanoparticles (Ag NPs).

PMID- 19405519
TI  - Plasmon enhancement and surface wave quenching for phase ratiometry in
      coextraction-based fluorosensors.
AB  - In this study, a novel fluorescence ratiometric sensing scheme is presented. Gold
      nanoparticles (GNPs) were lipophilized with dodecanethiol and incorporated in the
      ether phase of a coextraction based ammonium sensor. The novel concept of this
      sensing scheme is that the analyte response involves a movement of the
      fluorophore toward lipophilized GNPs in an organic phase. Properly arranged, the
      system benefits from surface plasmon enhancement as well as increased lossy
      surface wave quenching as the fluorophore moves toward the GNPs. Likely
      constructive scattering effects are also present due to some build-up of
      nanoparticle clusters. The sensor configuration significantly reduced the noise
      level, increased the ratiometric signal, and improved the limit of detection
      approximately 3 orders of magnitude as compared with the optical sensor without
      the nanoparticles and ion-selective ammonium electrodes. Qualitative and
      quantitative detection limits were 1.7 and 5.7 nM, respectively. The sensing
      scheme is versatile and can be utilized for many other ions.

PMID- 19405520
TI  - Excitation energies of zinc porphyrin in aqueous solution using long-range
      corrected time-dependent density functional theory.
AB  - We study the low-lying excited states of the zinc porphyrin molecule in aqueous
      solution using long-range corrected TDDFT. We report results using the CAM-B3LYP
      and CAM-PBE0 functionals and compare them with previously reported excited states
      based on high-level coupled cluster (CC) methods. The aqueous environment is
      treated via a QM/MM approach.

PMID- 19405521
TI  - Imidazolin-2-iminato complexes of rare earth metals with very short metal
      nitrogen bonds: experimental and theoretical studies.
AB  - The reactions of 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-imine (Im(Dipp)NH, 1
      H) with trimethylsilylmethyl lithium (LiCH(2)SiMe(3)) and anhydrous rare earth
      metal trichlorides MCl(3) afforded the imidazolin-2-iminato complexes
      [(1)MCl(2)(THF)(3)] (2a, M = Sc; 2b, M = Y; 2c, M = Lu) and [(1)GdCl(2)(THF)(2)]
      x [LiCl(THF)(2)] (2d). Treatment of complexes 2 with dipotassium
      cyclooctatetradienide, K(2)(C(8)H(8)) resulted in the formation of two- or three
      legged piano-stool complexes of the type [(eta(8)-C(8)H(8))M(1)(THF)(n)] (3a, M =
      Sc, n = 1; 3b, M = Y, n = 2; 3c, M = Lu, n = 2; 3d, M = Gd, n = 2). X-ray
      diffraction analyses of all eight complexes 2 and 3 revealed the presence of very
      short metal-nitrogen bonds, which are among the shortest ever observed for these
      elements. [(eta(8)-C(8)H(8))Sc(1)(THF)] (3a) reacted with 2,6-dimethylphenyl
      isothiocyanate (Xy-NCS) to form the [2 + 2]-cycloaddition product 4, which
      contains a thioureato-N,N' moiety. The related COT-titanium complex [(eta(8)
      C(8)H(8))TiCl(1)] (6) could be obtained from [(1)TiCl(3)] (5) by reaction with
      K(2)(C(8)H(8)) and was structurally characterized. As a theoretical analysis of
      the nature of the metal-nitrogen bond, density functional theory (DFT)
      calculations have been carried out for complexes 3a and 6 and also for the model
      complexes [(eta(8)-C(8)H(8))Sc(NIm(Me))] (7), [(eta(8)-C(8)H(8))Ti(NIm(Me))](+)
      (8), and [(eta(8)-C(8)H(8))Ti(NXy)] (9), revealing a marked similarity of the
      bonding in imidazolin-2-iminato and conventional imido metal complexes.

PMID- 19405522
TI  - Rapid optimization of MRM-MS instrument parameters by subtle alteration of
      precursor and product m/z targets.
AB  - Multiple reaction monitoring (MRM) is a highly sensitive method of targeted mass
      spectrometry (MS) that can be used to selectively detect and quantify peptides
      based on the screening of specified precursor peptide-to-fragment ion
      transitions. MRM-MS sensitivity depends critically on the tuning of instrument
      parameters, such as collision energy and cone voltage, for the generation of
      maximal product ion signal. Although generalized equations and values exist for
      such instrument parameters, there is no clear indication that optimal signal can
      be reliably produced for all types of MRM transitions using such an algorithmic
      approach. To address this issue, we have devised a workflow functional on both
      Waters Quattro Premier and ABI 4000 QTRAP triple quadrupole instruments that
      allows rapid determination of the optimal value of any programmable instrument
      parameter for each MRM transition. Here, we demonstrate the strategy for the
      optimizations of collision energy and cone voltage, but the method could be
      applied to other instrument parameters, such as declustering potential, as well.
      The workflow makes use of the incremental adjustment of the precursor and product
      m/z values at the hundredth decimal place to create a series of MRM targets at
      different collision energies that can be cycled through in rapid succession
      within a single run, avoiding any run-to-run variability in execution or
      comparison. Results are easily visualized and quantified using the MRM software
      package Mr. M to determine the optimal instrument parameters for each transition.

PMID- 19405523
TI  - Proteolytic fragments of chromogranins A and B represent major soluble components
      of chromaffin granules, illustrated by two-dimensional proteomics with NH(2)
      terminal Edman peptide sequencing and MALDI-TOF MS.
AB  - Neuroendocrine chromaffin granules of adrenal medulla represent regulated
      secretory vesicles that secrete neuropeptides and catecholamines which mediate
      cell-cell communication for physiological functions. This study addressed the
      identification of the major proteins in these secretory vesicles that provide
      dynamic storage and secretion of bioactive molecules. Proteins of the soluble
      compartment of the vesicles were separated by two-dimensional gels and subjected
      to NH(2)-terminal Edman sequencing for identification and determination of NH(2)
      termini. Results showed that proteolytic fragments of chromogranin A (CgA) and
      chromogranin B (CgB) represent the major proteins of these secretory vesicles.
      These fragments resulted from cleavage of their respective precursor proteins at
      dibasic and monobasic sites, which is consistent with the known cleavage
      specificities of prohormone processing enzymes. MALDI-TOF MS analyses of protein
      spots similar in molecular weight that possessed a range of pI values were
      represented by molecular forms of CgA and CgB proteins. These findings indicate
      the high prevalence of endogenous CgA and CgB proteolytic fragments that function
      in chromaffin secretory vesicles for release of bioactive molecules for cell-cell
      communication.

PMID- 19405525
TI  - Adsorbed CO on group 10 metal fragments: a DFT study.
AB  - DFT calculations on the helicopter and cartwheel rotations of one CO molecule
      adsorbed at the bridge site on metal-surface fragments, characterized by two
      (M(8)) or three (M(14)) metal-atom layers (M = Ni, Pd, Pt) were performed by the
      B3LYP[LANL2DZ+6-31 g(d,p)] method, to rationalize the adsorption energetics and
      the steric hindrance characteristics of surface CO molecules. Potential Energy
      Surfaces were obtained, either fixing the C-O bond-length or allowing it to
      change. The behavior of the three metals, as obtained from the study of the
      configurational space characterizing the CO adsorption on the fragments was
      explained on the basis of the interaction energies involved in the different CO/M
      systems. The results, obtained by using the M(14) fragments and varying both the
      C-O and the CO/M distances, point out that the CO adsorption on the Ni fragment
      is stabilized by surface-configurations in which the O atom is pointing toward a
      metal center. At variance, C-O bond elongation and stabilization occur on Pd when
      the O atom is situated between two palladium atoms. The CO adsorption on Pt
      displays similar characteristics to those observed on the Pd systems, but with
      the fundamental difference caused by the destabilization of the Pt-O interactions
      when the O atom is situated exactly between two Pt atoms. The calculations
      allowed us to estimate the IR spectroscopy frequency and band-broadening of the
      adsorbed CO stretching by a statistic analysis on a large set of energy / bond
      length computed data. Good agreement with the experimental results was obtained
      for all the metals, in particular concerning the frequencies. Reliable band
      broadenings were also obtained for the CO/Ni and CO/Pt systems, while the lower
      band-broadening value for the CO/Pd system was related to the small extent of the
      configurational sampling space.

PMID- 19405526
TI  - Comparison of nonbinary similarity coefficients for similarity searching,
      clustering and compound selection.
AB  - Several recent studies have compared the relative performance of a selection of
      similarity coefficients when applied to chemical databases represented by binary
      fingerprints. Considerable variation in performance, when used for
      (dis)similarity-based techniques, such as similarity searching, database
      clustering, and dissimilarity-based compound selection, has been reported, the
      reasons for which are closely related to molecular size. For many of these
      similarity coefficients, an alternative form can be derived which is applicable
      to sets of nonbinary data, such as calculated or measured physicochemical
      properties, or counts of substructural fragments. Here we report on several
      studies which have been undertaken to investigate the relative performance of
      twelve coefficients when applied to nonbinary data using such (dis)similarity
      based techniques. Results suggest that no single coefficient is appropriate for
      all methodologies investigated and that the size bias detected with binary data
      is not as apparent when the data and, hence, coefficient are nonbinary in nature.

PMID- 19405527
TI  - Optimization of ultrasound-assisted extraction of phenolic compounds,
      antioxidants, and anthocyanins from grape (Vitis vinifera) seeds.
AB  - Important functional components from Campbell Early grape seed were extracted by
      ultrasound-assisted extraction (UAE) technology. The experiments were carried out
      according to a five level, three variable central composite rotatable design
      (CCRD). The best possible combinations of ethanol concentration, extraction
      temperature, and extraction time with the application of ultrasound were obtained
      for the maximum extraction of phenolic compounds, antioxidant activities, and
      anthocyanins from grape seed by using response surface methodology (RSM). Process
      variables had significant effect on the extraction of functional components with
      extraction time being highly significant for the extraction of phenolics and
      antioxidants. The optimal conditions obtained by RSM for UAE from grape seed
      include 53.15% ethanol, 56.03 degrees C temperature, and 29.03 min time for the
      maximum total phenolic compounds (5.44 mg GAE/100 mL); 53.06% ethanol, 60.65
      degrees C temperature, and 30.58 min time for the maximum antioxidant activity
      (12.31 mg/mL); and 52.35% ethanol, 55.13 degrees C temperature, and 29.49 min
      time for the maximum total anthocyanins (2.28 mg/mL). Under the above-mentioned
      conditions, the experimental total phenolics were 5.41 mg GAE/100 mL, antioxidant
      activity was 12.28 mg/mL, and total anthocyanins were 2.29 mg/mL of the grape
      seed extract, which is well matched with the predicted values.

PMID- 19405524
TI  - Functionalized congener approach to the design of ligands for G protein-coupled
      receptors (GPCRs).
AB  - Functionalized congeners, in which a chemically functionalized chain is
      incorporated at an insensitive site on a pharmacophore, have been designed from
      the agonist and antagonist ligands of various G protein-coupled receptors
      (GPCRs). These chain extensions enable a conjugation strategy for detecting and
      characterizing GPCR structure and function and pharmacological modulation. The
      focus in many studies of functionalized congeners has been on two families of
      GPCRs: those responding to extracellular purines and pyrimidines-i.e., adenosine
      receptors (ARs) and P2Y nucleotide receptors. Functionalized congeners of small
      molecule as ligands for other GPCRs and non-G protein coupled receptors have also
      been designed. For example, among biogenic amine neurotransmitter receptors,
      muscarinic acetylcholine receptor antagonists and adrenergic receptor ligands
      have been studied with a functionalized congener approach. Adenosine A(1), A(2A),
      and A(3) receptor functionalized congeners have yielded macromolecular
      conjugates, irreversibly binding AR ligands for receptor inactivation and cross
      linking, radioactive probes that use prosthetic groups, immobilized ligands for
      affinity chromatography, and dual-acting ligands that function as binary drugs.
      Poly(amidoamine) dendrimers have served as nanocarriers for covalently conjugated
      AR functionalized congeners. Rational methods of ligand design derived from
      molecular modeling and templates have been included in these studies. Thus, the
      design of novel ligands, both small molecules and macromolecular conjugates, for
      studying the chemical and biological properties of GPCRs have been developed with
      this approach, has provided researchers with a strategy that is more versatile
      than the classical medicinal chemical approaches.

PMID- 19405529
TI  - High performance zeolite LTA pervaporation membranes on ceramic hollow fibers by
      dipcoating-wiping seed deposition.
AB  - We demonstrate for the first time that by one single hydrothermal synthesis a
      zeolite LTA membrane with a high flux of 9.0 kg/m(2) h and high water/ethanol
      separation factor of 10,000 could be formed on a ceramic hollow fiber that is
      known for its ability to form a compact module. The flux is the highest reported
      in the literatures. A novel seeding method, dipcoating-wiping, is key to
      obtaining zeolite membranes with high separation performance because it
      reproducibly produces a uniform and trace seed layer on the support. This new
      seeding method is expected to have serious implications for making defect-free
      zeolite films and membranes for many applications. The membranes reported here
      have the potential to solve the key problems that have prevented zeolite
      membranes from widespread use for biofuel production.

PMID- 19405530
TI  - Carbon nanotube growth from diamond.
AB  - We demonstrate that nanosize diamond particles in a stable solid phase can act as
      nuclei for carbon nanotube (CNT) growth by chemical vapor deposition. This growth
      process is explained by a new growth mechanism, where the surface diffusion of
      carbon adatoms on the solid surface of nanoparticles plays an important role,
      contrary to the bulk diffusion in conventional metal catalysts. The use of
      diamond nanoparticles overcomes the issues of deactivation due to fusion with
      each other or reaction with substrate materials in the CNT growth using
      conventional metal catalysts and promotes high-density CNT growth from highly
      dense nanoparticles on any substrate.

PMID- 19405528
TI  - Potent cytotoxic C-11 modified geldanamycin analogues.
AB  - 17-Allylamino-17-demethoxygeldanamycin (17-AAG) inhibits the activity of Hsp90,
      an important target for treatment of cancers. In an effort to identify analogues
      of geldanamycin (GDM) with properties superior to those of 17-AAG, we synthesized
      C-11 modified derivatives of GDM including ethers, esters, carbazates, ketones,
      and oximes and measured their affinity for Hsp90 and their ability to inhibit
      growth of human cancer cells. In accordance with crystal structures reported for
      complexes of GDMs with Hsp90, bulky groups attached to C-11 interfered with Hsp90
      binding while smaller groups such as 11-O-methyl allowed Hsp90 binding. In
      addition, these analogues also showed in vitro cytotoxicity against human cancer
      cell lines. Esterification of the 11-OH of 17-AAG eliminated Hsp90 binding in
      vitro. The readily hydrolyzed esters acted as prodrugs during the measurement of
      cytotoxicity. Thus, during these experiments, the esters were hydrolyzed,
      releasing 17-AAG. Several 11-O-methyl-17-alkylaminogeldanamycin analogues were
      identified with improved potency relative to 17-AAG.

PMID- 19405531
TI  - Self-organizing functional materials via ionic self assembly: porphyrins H- and J
      aggregates on synthetic chrysotile nanotubes.
AB  - Positively charged, synthetic chrysotile nanotubes act as inorganic tectons
      supporting H- and J-type aggregates of anionic porphyrins with markedly different
      optical properties, making these nanohybrid materials of interest for application
      in nanotechnology.

PMID- 19405532
TI  - Bifunctional acyltransferase/decarboxylase LnmK as the missing link for beta
      alkylation in polyketide biosynthesis.
AB  - Beta-alkylations contribute to the vast structural diversity displayed by
      polyketide natural products. A unified pathway has been proposed for introduction
      of both beta-methyl and beta-ethyl branches catalyzed by hydroxymethylglutaryl
      CoA synthase homologues that utilize acetyl- or propionyl-S-acyl carrier protein
      (ACP) as a substrate. While the origin of acetyl-S-ACP has been established, that
      of propionyl-S-ACP remains unknown. Here we report the characterization of LnmK
      from the leinamycin biosynthetic machinery as a bifunctional
      acyltransferase/decarboxylase (AT/DC) that derives propionyl-S-ACP from
      methylmalonyl-CoA, accounting for the missing link of the beta-ethyl or propionyl
      branch in polyketide biosynthesis. LnmK represents an emerging family of novel
      AT/DC enzymes and could be exploited by combinatorial biosynthesis methods to
      engineer novel polyketides, especially those with beta-alkyl branches.

PMID- 19405534
TI  - Association of highly compact type II diabetes related islet amyloid polypeptide
      intermediate species at physiological temperature revealed by diffusion NMR
      spectroscopy.
AB  - Self-association of human islet amyloid polypeptide (hIAPP) is correlated with
      the development of type II diabetes by the disruption of cellular homeostasis in
      islet cells through the formation of membrane-active oligomers. The toxic species
      of hIAPP responsible for membrane damage has not been identified. In this study,
      we show by pulsed field gradient NMR spectroscopy that the monomeric form of the
      toxic, amyloidogenic human variant of IAPP (hIAPP) adopts a temperature dependent
      compact folded conformation that is absent in both the nontoxic and
      nonamyloidogenic rat variant of IAPP and absent in hIAPP at low temperatures,
      suggesting this compact form of monomeric hIAPP may be linked to its later
      aggregation and cytotoxicity. In addition to the monomeric form of hIAPP, a large
      oligomeric species greater than 100 nm in diameter is also present but does not
      trigger the nucleation-dependent aggregation of IAPP at 4 degrees C, indicating
      the large oligomeric species may be an off-pathway intermediate that has been
      predicted by kinetic models of IAPP fiber formation. Furthermore, analysis of the
      polydispersity of the calculated diffusion values indicates small oligomeric
      species of hIAPP are absent in agreement with a recent ultracentrifugation study.
      The absence of small oligomeric species in solution suggests the formation of
      small, well-defined ion channels by hIAPP may proceed by aggregation of monomeric
      IAPP on the membrane, rather than by the insertion of preformed structured
      oligomers from the solution state as has been proposed for other amyloidogenic
      proteins.

PMID- 19405535
TI  - Spin trapping of Au-H intermediate in the alcohol oxidation by supported and
      unsupported gold catalysts.
AB  - Electron paramagnetic resonance (EPR) spectroscopy and spin trapping were used to
      explore the mechanism of alcohol oxidation over gold catalysts. Reaction of
      secondary alcohols with supported and unsupported gold catalysts (e.g.,
      Au/CeO(2), polymer-incarcerated Au nanoparticles, PPh(3)-protected Au
      nanoparticles) in the presence of spin traps led to the formation of a hydrogen
      spin adduct. Using isotope labeling, we confirmed that the hydrogen in the spin
      adduct originates from the cleavage of the C-H bond in the alcohol molecule. The
      formation of the hydrogen spin adduct most likely results from the abstraction of
      hydrogen from the Au surface by a spin trap. These results thus strongly suggest
      intermediate formation of Au-H species during alcohol oxidation. The role of
      oxygen in this mechanism is to restore the catalytic activity rather than oxidize
      alcohol. This was further confirmed by carrying out gold-catalyzed alcohol
      oxidation in the absence of oxygen, with nitroxides as hydrogen abstractors. The
      support (e.g., metal oxides) can activate oxygen and act as an H abstractor from
      the gold surface and hence lead to a faster recovery of the activity. Peroxyl
      radicals were also observed during alcohol oxidation, consistent with a free
      radical autoxidation mechanism. However, this mechanism is likely to be a minor
      side reaction, which does not lead to the formation of an appreciable amount of
      oxidation products.

PMID- 19405533
TI  - Long-distance proton transfer with a break in the bacteriorhodopsin active site.
AB  - Bacteriorhodopsin is a proton-pumping membrane protein found in the plasma
      membrane of the archaeon Halobacterium salinarium. Light-induced isomerization of
      the retinal chromophore from all-trans to 13-cis leads to a sequence of five
      conformation-coupled proton transfer steps and the net transport of one proton
      from the cytoplasmic to the extracellular side of the membrane. The mechanism of
      the long-distance proton transfer from the primary acceptor Asp85 to the
      extracellular proton release group during the O --> bR is poorly understood.
      Experiments suggest that this long-distance transfer could involve a transient
      state [O] in which the proton resides on the intermediate carrier Asp212. To
      assess whether the transient protonation of Asp212 participates in the
      deprotonation of Asp85, we performed hybrid Quantum Mechanics/Molecular Mechanics
      proton transfer calculations using different protein structures and with
      different retinal geometries and active site water molecules. The structural
      models were assessed by computing UV-vis excitation energies and C=O vibrational
      frequencies. The results indicate that a transient [O] conformer with protonated
      Asp212 could indeed be sampled during the long-distance proton transfer to the
      proton release group. Our calculations suggest that, in the starting proton
      transfer state O, the retinal is strongly twisted and at least three water
      molecules are present in the active site.

PMID- 19405536
TI  - Destruction of the hydration shell around tetraalkylammonium ions at the
      electrochemical interface.
AB  - The structure and behavior of the hydration shells around tetraethyl-, -propyl-,
      and -butylammonium ions (Et(4)N(+), Pr(4)N(+), and Bu(4)N(+), respectively) at a
      CO-covered Pt electrode was studied by surface-enhanced IR absorption
      spectroscopy. Selective concentration of cations at the electrochemical interface
      by controlling the applied potential facilitates the observation of the hydration
      shells without interference from hydrated anions. We report for the first time
      that the hydration shells around Pr(4)N(+) and Bu(4)N(+) are decomposed at
      sufficiently negative potentials because of the strong electrostatic attraction
      with the surface. On the other hand, the hydration shell around Et(4)N(+), the
      smallest ion, is more stable and does not decompose in the potential range
      examined. The difference in the stability can be ascribed to the difference in
      the size of the central cation. On the other hand, the hydration shells are
      easily deconstructed on a bare Pt surface because of the stronger interaction
      with the surface.

PMID- 19405537
TI  - Mutations in the FMN domain modulate MCD spectra of the heme site in the
      oxygenase domain of inducible nitric oxide synthase.
AB  - The nitric oxide synthase (NOS) output state for NO production is a complex of
      the flavin mononucleotide (FMN)-binding domain and the heme domain, and thereby
      it facilitates the interdomain electron transfer from the FMN to the catalytic
      heme site. Emerging evidence suggests that interdomain FMN-heme interactions are
      important in the formation of the output state because they guide the docking of
      the FMN domain to the heme domain. In this study, notable effects of mutations in
      the adjacent FMN domain on the heme structure in a human iNOS bidomain
      oxygenase/FMN construct have been observed by using low-temperature magnetic
      circular dichroism (MCD) spectroscopy. The comparative MCD study of wild-type and
      mutant proteins clearly indicates that a properly docked FMN domain contributes
      to the observed L-Arg perturbation of the heme MCD spectrum in the wild-type
      protein and that the conserved surface residues in the FMN domain (E546 and E603)
      play key roles in facilitating a productive alignment of the FMN and heme domains
      in iNOS.

PMID- 19405538
TI  - Chiral lanthanum(III)-binaphthyldisulfonate complexes for catalytic
      enantioselective Strecker reaction.
AB  - A catalytic enantioselective Strecker reaction catalyzed by novel chiral
      lanthanum(III)-binaphthyl disulfonate complexes was developed. The key to
      promoting the reactions was a semistoichiometric amount of AcOH or i-PrCO(2)H,
      which takes advantage of HCN generation in situ. The corresponding cyanation
      products were obtained in high yields and with high enantioselectivities.

PMID- 19405539
TI  - Lipid-dependent effects of halothane on gramicidin channel kinetics: a new role
      for lipid packing stress.
AB  - We find that the sensitivity of gramicidin A channels to the anesthetic halothane
      is highly lipid dependent. Specifically, exposure of membranes made of lamellar
      DOPC to halothane in concentrations close to clinically relevant reduces channel
      lifetimes by 1 order of magnitude. At the same time, gramicidin channels in
      membranes of nonlamellar DOPE are affected little, if at all, by halothane. We
      attribute this difference in channel behavior to a difference in the stress of
      lipid packing into a planar lipid bilayer, wherein the higher stress of DOPE
      packing reduces the degree of halothane partitioning into the hydrophobic
      interior.

PMID- 19405540
TI  - Synthesis, short-range structure, and electrochemical properties of new phases in
      the Li-Mn-N-O system.
AB  - A crystal-chemical exploration of part of the Li-Mn-N-O system was carried out.
      Several samples were synthesized using Li(3)N, Mn(x)N and Li(2)O and
      characterized with chemical analysis, XRD, XAS, and NMR. An increase in the
      starting proportion of Li(2)O increases the amounts of lithium and oxygen in the
      compounds, but, according to the XANES Mn K-edge spectra, all the oxynitrides
      still contain Mn(5+) ions preferentially coordinated by N(3-), forming [MnN(4)]
      tetrahedra. The analysis of the position of these samples in the compositional
      Li(3)N-Li(2)O-MnN(x) ternary phase diagram and the plot of their cell parameters
      against the oxygen molar fraction indicates that all the oxynitrides belong to
      the same tie-line, which also includes Li(2)O but not Li(7)MnN(4). Although the
      XRD patterns suggest that these samples crystallize in a disordered antifluorite
      type structure, the analysis of the (6)Li NMR data indicates that short-range
      ordering does exist. The performance as electrode materials in lithium batteries
      of the synthesized samples was also evaluated. Li(7.9)MnN(3.2)O(1.6) was shown to
      be the most attractive candidate because of its higher capacity values and
      improved retention upon cycling with respect to the other members of the series.

PMID- 19405541
TI  - Experimental insight into the radiation resistance of zirconia-based americium
      ceramics.
AB  - Our works shows that the americium pyrochlore (241)Am(2)Zr(2)O(7) undergoes a
      phase transition to a defect-fluorite structure along with an unusual volume
      contraction when subjected to internal radiation from alpha-emitting actinides.
      Disorder relaxation proceeds through the simultaneous formation of cation
      antisites and oxygen Frenkel pairs. X-ray absorption spectroscopy at the Am-L(II)
      and the Zr-K edges reveals that Am-O polyhedra show an increasing disorder with
      increasing exposure. In contrast, the Zr-O polyhedral units remain highly
      ordered, while rotating along edges and corners, thereby reducing the structural
      strain imposed by the growing disorder around americium. We believe it is this
      particular property of the compound that provides the remarkable resistance to
      radiation (>9.4 x 10(18) alpha-decay events g(-1) or 0.80 dpa).

PMID- 19405542
TI  - Photochemically-induced acid generation from 18-molybdodiphosphate and 18
      tungstodiphosphate within poly(2-hydroxyethyl methacrylate) films.
AB  - The capability of ammonium 18-molybdodiphosphate, (NH(4))(6)P(2)Mo(18)O(62)
      (Mo(18)(6-)), and ammonium 18-tungstodiphosphate, (NH(4))(6)P(2)W(18)O(62)
      (W(18)(6-)), to photochemically generate acid within films of a polymer with
      hydroxylic functional groups (namely, within poly(2-hydroxyethyl methacrylate)
      (PHEMA) films) is demonstrated. Upon UV irradiation, both 2:18 polyoxometalates
      (POMs) investigated are reduced with concomitant oxidation of PHEMA and
      generation of acid, which subsequently catalyzes the cross-linking of PHEMA. The
      photoacid generation is mainly evidenced by monitoring the protonation of an
      appropriate acid indicator (4-dimethylamino-4'-nitrostilbene) with UV
      spectroscopy and by photolithographic imaging experiments. By comparing the
      efficiency of both POMs to induce acid-catalyzed cross-linking of PHEMA under
      similar conditions, the W(18)(6-) ion is found to be more efficient in photoacid
      generation than the Mo(18)(6-) ion. Imaging of the POM-containing PHEMA films
      through UV photolithographic processing is demonstrated. In that process, both
      POMs can be entirely leached during the development step by using pure water as a
      developer, resulting in patterned PHEMA films. This characteristic renders the
      investigated POMs attractive materials for applications, especially in the area
      of biomaterials, where removal of the photoacid generator from the film at the
      end of the process is desirable.

PMID- 19405543
TI  - A helix swapping study of two protein cages.
AB  - Protein cages have been the focus of studies across multiple scientific
      disciplines. They have been used to deliver drugs, as templates for
      nanostructured materials, as substrates in the development of bio-orthogonal
      chemistry, and to restrict diffusion to study spatially confined reactions.
      Although their monomers fold into four-helix bundle structures, two cage
      proteins, DPS and BFR, self-assemble to form a 12-mer with tetrahedral symmetry
      and an octahedrally symmetric 24-mer, respectively. These monomers share strong
      similarities of both sequence and tertiary structure. However, they differ in the
      presence of a short additional helix. In BFR, the fifth helix is at the C
      terminus and is positioned along the 4-fold symmetry axis, whereas with DPS, an
      extra helix helps to define the 2-fold axis in the cage and is located between
      the second and third helices in the monomer bundle. In an attempt to investigate
      if these short helices govern protein assembly, mutants were designed and
      produced that delete and swap these minidomains. All mutants form highly helical
      structures that unfold cooperatively as evidenced by thermal melting followed by
      circular dichroism. Dynamic light scattering, size exclusion chromatography, and
      sedimentation equilibrium experiments demonstrated that although many of the BFR
      mutants do not self-assemble and form lower-order complexes, many DPS mutants
      could form cages despite their unnatural design. Taken together, our data
      indicate that the BC helix is less important than the E helix for overall cage
      self-assembly, suggesting that dimerization may not play a role in nanostructure
      formation that is as key as previously assumed. Additionally, we found that
      fusing the minidomain from BFR onto DPS results in a mutant that assembles into a
      homogeneous population of a novel protein oligomer. This assembled cage while
      still formed from 12 subunits is larger in overall shape than that of the native
      protein.

PMID- 19405544
TI  - Structure-activity relations of nanolipoblockers with the atherogenic domain of
      human macrophage scavenger receptor A.
AB  - Oxidized low density lipoprotein (oxLDL) uptake by macrophages is mediated by
      scavenger receptors and leads to unregulated cholesterol accumulation. Micellar
      nanolipoblockers (NLBs) consist of alkyl chains and polyethylene glycol on mucic
      acid. NLBs functionalized with anionic groups inhibit oxLDL uptake via the
      scavenger receptor A (SR-A). Molecular modeling and docking approaches were used
      to understand the structure-activity relationship (SAR) between NLBs and SR-A.
      Six NLB models were docked to the SR-A homology model to investigate charge
      placement and clustering. NLB models with the most favorable binding energy were
      also the most effective oxLDL inhibitors in THP-1 macrophages. Mutant SR-A models
      were generated by replacing charged residues with alanine. All charged residues
      in the region were necessary, with Lys60, Lys63, and Lys66 having the greatest
      effect on binding. We hypothesize that structural studies aided by theoretical
      modeling and docking can be used to design promising NLB candidates with optimal
      binding properties.

PMID- 19405545
TI  - Non-cytotoxic silver nanoparticle-polysaccharide nanocomposites with
      antimicrobial activity.
AB  - In this work we study (i) the formation and stabilization of silver nanoparticles
      in a bioactive chitosan-derived polysaccharide solution, (ii) the antimicrobial
      properties, either in solution or in 3D hydrogel structures, obtained by mixtures
      with the polysaccharide alginate, and (iii) the cytotoxicity of the latter
      nanocomposite materials on different eukaryotic cell lines. Antimicrobial results
      show that these nanocomposite systems display a very effective bactericidal
      activity toward both Gram+ and Gram- bacteria. However, the hydrogel does not
      show any cytotoxic effect toward three different eukaryotic cell lines. This is
      due to the fact that the nanoparticles, immobilized in the gel matrix, can exert
      their antimicrobial activity by simple contact with the bacterial membrane, while
      they can not be uptaken and internalized by eukaryotic cells. This novel finding
      could advantageously contribute to responding to the growing concerns on the
      toxicity of nanoparticles and facilitate the use of silver-biopolymer composites
      in the preparation of biomaterials.

PMID- 19405546
TI  - The relationship between nanoscale architecture and charge transport in
      conjugated nanocrystals bridged by multichromophoric Polymers.
AB  - We report on the self-assembly and the electrical characterization of bicomponent
      films consisting of an organic semiconducting small molecule blended with a rigid
      polymeric scaffold functionalized in the side chains with monomeric units of the
      same molecule. The molecule and polymer are a perylene-bis(dicarboximide) monomer
      (M-PDI) and a perylene-bis(dicarboximide)-functionalized poly(isocyanopeptide) (P
      PDI), which have been codeposited on SiO(x) and mica substrates from solution.
      These bicomponent films have been characterized by atomic force microscopy (AFM)
      and Kelvin probe force microscopy (KPFM), revealing the relationship between
      architecture and function for various supramolecular nanocrystalline arrangements
      at a nanometer spatial resolution. Monomer-polymer interactions can be controlled
      by varying solvent and/or substrate polarity, so that either the monomer packing
      dictates the polymer morphology or vice versa, leading to a morphology exhibiting
      M-PDI nanocrystals connected with each other by P-PDI polymer wires. Compared to
      pure M-PDI or P-PDI films, those bicomponent films that possess polymer
      interconnections between crystallites of the monomer display a significant
      improvement in electrical connectivity and a 2 orders of magnitude increase in
      charge carrier mobility within the film, as measured in thin film transistor
      (TFT) devices. Of a more fundamental interest, our technique allows the bridging
      of semiconducting crystals, without the formation of injection barriers at the
      connection points.

PMID- 19405547
TI  - Pharmacotherapy for the secondary prevention of stroke.
AB  - Stroke recurrence continues to be the major risk for stroke survivors. Risk
      factor control and antithrombotic medication are two major strategies for
      patients with a prior stroke or transient ischaemic attack (TIA) to prevent
      stroke recurrence. Hypertension, dyslipidaemia and diabetes mellitus are risk
      factors that are modifiable by pharmacotherapy, as well as by lifestyle
      modification. Antihypertensive treatment is recommended for secondary stroke
      prevention for both hypertensive and normotensive patients. HMG-CoA reductase
      inhibitor (statin) therapy to obtain an intensive lipid-lowering effect is also
      highly recommended. A recent trial indicated that treatment with pioglitazone is
      effective for patients with type 2 diabetes. However, the evidence for risk
      factor control is relatively new, and further studies are needed for better
      evidence-based prevention. For patients with noncardioembolic ischaemic stroke or
      TIA, antiplatelet therapy rather than anticoagulation is recommended to reduce
      the risk of recurrent stroke and other cardiovascular events. Aspirin was the
      first antiplatelet agent to have established evidence for secondary stroke
      prevention. Currently, aspirin monotherapy, the combination of aspirin and
      extended-release dipyridamole, and clopidogrel monotherapy are recommended as the
      major choices. The combination of aspirin and clopidogrel is not routinely
      recommended. Adjusted-dose warfarin with a target international normalized ratio
      range between 2.0 and 3.0 is recommended after an ischaemic stroke or TIA
      associated with nonvalvular atrial fibrillation. Bleeding complications are a
      critical problem with antithrombotic therapy. Warfarin, as well as antiplatelet
      therapy, increases the incidence of bleeding and worsens the severity of the
      bleeding events. Choosing antithrombotic agents and their intensity (dosage)
      appropriate to the stroke mechanism and the patient's condition are essential for
      secondary stroke prevention.

PMID- 19405549
TI  - Medical expulsive therapy for distal ureteral stones.
AB  - Although minimally invasive treatments for ureteral stones are efficacious, they
      are not free of complications and are associated with high cost. Medical
      expulsive therapy (MET) has recently emerged as an alternative strategy for the
      initial management of small distal ureteral stones. A MEDLINE search was
      undertaken to evaluate all currently available data on efficacy and safety of MET
      therapy in such patients. The specific mechanism of action on the ureteral smooth
      muscle and the emerging evidence of the efficacy (defined as either an increase
      in expulsion rate or a decrease in time to expulsion) and low-risk profile
      suggest that alpha-adrenergic receptor antagonists (alpha-blockers) and calcium
      channel antagonists should be the initial medical treatment in patients amenable
      to conservative therapy. NSAIDs and anticholinergics have not shown efficacy as
      single agents or in combination with alpha-blockers or nifedipine.
      Corticosteroids may provide a small additive effect when combined with either
      alpha-blockers or nifedipine.

PMID- 19405548
TI  - Endometriosis: current therapies and new pharmacological developments.
AB  - Endometriosis is a chronic inflammatory condition that is responsive to
      management with steroids. The establishment of a steady hormonal environment and
      inhibition of ovulation can temporarily suppress ectopic implants and reduce
      inflammation as well as associated pain symptoms. In terms of pharmacological
      management, the currently available agents are not curative, and treatment often
      needs to be continued for years or until pregnancy is desired. Similar efficacy
      has been observed from the various therapies that have been investigated for
      endometriosis. Accordingly, combined oral contraceptives and progestins, based on
      their favourable safety profile, tolerability and cost, should be considered as
      first-line options, as an alternative to surgery and for post-operative adjuvant
      use. In situations where progestins and oral contraceptives prove ineffective,
      are poorly tolerated or are contraindicated, gonadotrophin-releasing hormone
      analogues, danazol or gestrinone may be used. Future therapeutic options for
      managing endometriosis must compare favourably against existing agents before
      they can be considered for inclusion into current practice. Finally, as
      reproductive prognosis is not ameliorated by medical treatment, it is not
      indicated for women seeking conception.

PMID- 19405551
TI  - Olmesartan medoxomil/amlodipine.
AB  - black triangle Olmesartan medoxomil/amlodipine is a fixed-dose combination of
      olmesartan medoxomil and amlodipine, both established antihypertensive agents.
      Dose titration with the individual constituent drugs is recommended before
      switching to the equivalent fixed-dose combination. black triangle In a
      randomized, double-blind, factorial trial in patients with mild to severe
      hypertension, 8 weeks of olmesartan medoxomil/amlodipine was more effective in
      reducing diastolic BP (DBP) and systolic BP (SBP) than placebo or equivalent
      dosages of olmesartan medoxomil or amlodipine as monotherapy. black triangle In
      two randomized, double-blind trials in patients with moderate to severe
      hypertension not adequately treated with amlodipine or olmesartan medoxomil
      monotherapy, 8 weeks of olmesartan medoxomil/amlodipine 20 mg/5 mg, 40 mg/5 mg or
      40 mg/10 mg per day was more effective in reducing DBP and SBP than continuing
      treatment with olmesartan medoxomil 20 mg/day or amlodipine 5 mg/day monotherapy.
      black triangle More patients receiving olmesartan medoxomil/amlodipine at
      approved dosages than monotherapy recipients at equivalent dosages reached BP
      goals (42.5-51.0% vs 21.1-36.3% in the factorial trial and 44.5-54% vs 28.5-30%
      in the monotherapy comparisons). black triangle In the comparison with amlodipine
      monotherapy, >70% of olmesartan medoxomil/amlodipine recipients, some requiring
      upwards dosage adjustment, met BP goals. black triangle Olmesartan
      medoxomil/amlodipine was generally well tolerated in clinical trials. Peripheral
      oedema was significantly less common in olmesartan medoxomil/amlodipine 40 mg/10
      mg per day than amlodipine monotherapy 10 mg/day recipients.

PMID- 19405552
TI  - Fesoterodine.
AB  - black triangle Fesoterodine is a muscarinic receptor antagonist that is rapidly
      and extensively converted to the active and more potent metabolite 5
      hydroxymethyltolterodine. The drug is approved for once-daily oral administration
      in patients with overactive bladder syndrome (OAB). black triangle In two large,
      12-week, randomized, double-blind, multicentre, phase III trials, oral
      fesoterodine 4 or 8 mg once daily improved the symptoms of OAB (frequency of
      micturition, urgency and urge incontinence) significantly more than placebo.
      black triangle Furthermore, significantly more patients receiving fesoterodine 4
      or 8 mg once daily had a positive response to therapy than those receiving
      placebo, as determined by a treatment questionnaire. black triangle Health
      related quality of life was improved to a significantly greater extent in
      patients with OAB who received fesoterodine 4 or 8 mg once daily than in those
      who received placebo in a post hoc analysis of pooled data from the phase III
      trials. black triangle Fesoterodine 4 or 8 mg once daily was generally well
      tolerated in patients with OAB; the most frequent adverse event was dry mouth,
      which was generally mild to moderate in severity.

PMID- 19405554
TI  - Theory of competitive adsorption-nucleation in polypeptide-mediated
      biomineralization.
AB  - The process of biomineralization occurs in various natural organisms with
      astonishing ease by the interplay between polymers and mineralization but eludes
      a fundamental understanding. In addressing how specific polymers direct selection
      of mineral morphologies and their growth kinetics, we present a new model based
      on a competition between adsorption of polymers onto selective interfaces and
      nucleation growth of minerals. The model is couched in the context of zinc oxide,
      crystallized from solutions containing polypeptides, where systematic
      experimental data are available. Adsorption of the polymer onto certain
      crystallographic planes leads to poisoning of the surfaces, and as a result these
      surfaces are arrested from further growth. By this mechanism, originally
      disfavored growth sectors are promoted to grow by suppressing the initial faster
      growing sectors. Our theory predicts the relative growth rates of different
      sectors altered by selective adsorption of polymers. Theoretical prediction of
      the dependence of the aspect ratio on polypeptide concentration is in agreement
      with experimental results, providing credence to the applicability of adsorption
      nucleation models to polymer-mediated biomineralization.

PMID- 19405553
TI  - Ferric carboxymaltose: a review of its use in iron-deficiency anaemia.
AB  - Ferric carboxymaltose (Ferinject(R)), a novel iron complex that consists of a
      ferric hydroxide core stabilized by a carbohydrate shell, allows for controlled
      delivery of iron to target tissues. Administered intravenously, it is effective
      in the treatment of iron-deficiency anaemia, delivering a replenishment dose of
      up to 1000 mg of iron during a minimum administration time of </=15 minutes.
      Results of several randomized trials have shown that intravenously administered
      ferric carboxymaltose rapidly improves haemoglobin levels and replenishes
      depleted iron stores in various populations of patients with iron-deficiency
      anaemia, including those with inflammatory bowel disease, heavy uterine bleeding,
      postpartum iron-deficiency anaemia or chronic kidney disease. It was well
      tolerated in clinical trials. Ferric carboxymaltose is, therefore, an effective
      option in the treatment of iron-deficiency anaemia in patients for whom oral iron
      preparations are ineffective or cannot be administered. Ferric carboxymaltose is
      a macromolecular ferric hydroxide carbohydrate complex, which allows for
      controlled delivery of iron within the cells of the reticuloendothelial system
      and subsequent delivery to the iron-binding proteins ferritin and transferrin,
      with minimal risk of release of large amounts of ionic iron in the serum.
      Intravenous administration of ferric carboxymaltose results in transient
      elevations in serum iron, serum ferritin and transferrin saturation, and,
      ultimately, in the correction of haemoglobin levels and replenishment of depleted
      iron stores. The total iron concentration in the serum increased rapidly in a
      dose-dependent manner after intravenous administration of ferric carboxymaltose.
      Ferric carboxymaltose is rapidly cleared from the circulation and is distributed
      primarily to the bone marrow ( approximately 80%) and also to the liver and
      spleen. Repeated weekly administration of ferric carboxymaltose does not result
      in accumulation of transferrin iron in patients with iron-deficiency anaemia.
      Intravenously administered ferric carboxymaltose was effective in the treatment
      of iron-deficiency anaemia in several 6- to 12-week, randomized, open-label,
      controlled, multicentre trials in various patient populations, including those
      with inflammatory bowel disease, heavy uterine bleeding or postpartum iron
      deficiency anaemia, and those with chronic kidney disease not undergoing or
      undergoing haemodialysis. In most trials, patients received either ferric
      carboxymaltose equivalent to an iron dose of </=1000 mg (or 15 mg/kg in those
      weighing <66 kg) administered over </=15 minutes (subsequent doses administered
      at 1-week intervals) or oral ferrous sulfate at a dose equivalent to 65 mg iron
      three times daily or 100 mg iron twice daily. In one trial, patients with chronic
      kidney disease undergoing haemodialysis received 200 mg of iron intravenously
      either as ferric carboxymaltose or iron sucrose administered into the
      haemodialysis line two to three times weekly. In all trials, ferric
      carboxymaltose was administered until each patient had received his or her
      calculated total iron replacement dose. Haemoglobin-related outcomes improved in
      patients with iron-deficiency anaemia receiving ferric carboxymaltose. Treatment
      with ferric carboxymaltose was associated with rapid and sustained increases from
      baseline in haemoglobin levels. Ferric carboxymaltose was considered to be as
      least as effective as ferrous sulfate with regard to changes from baseline in
      haemoglobin levels or the proportion of patients achieving a haematopoietic
      response at various timepoints. In general, improvements in haemoglobin levels
      were more rapid with ferric carboxymaltose than with ferrous sulfate. In patients
      with chronic kidney disease undergoing haemodialysis, ferric carboxymaltose was
      at least as effective as iron sucrose. Ferric carboxymaltose also replenished
      depleted iron stores and improved health-related quality-of-life (HR-QOL) in
      patients with iron-deficiency anaemia. Recipients of ferric carboxymaltose
      demonstrated improvements from baseline in serum ferritin levels and transferrin
      saturation, as well as improvements from baseline in HR-QOL assessment scores.
      Ferric carboxymaltose was at least as effective as ferrous sulfate with regard to
      endpoints related to serum ferritin levels, transferrin saturation and HR-QOL.
      Ferric carboxymaltose was well tolerated in clinical trials in patients with iron
      deficiency anaemia, with most drug-related adverse events considered to be mild
      to moderate in severity. Commonly reported drug-related adverse events include
      headache, dizziness, nausea, abdominal pain, constipation, diarrhoea, rash and
      injection-site reactions. The incidence of drug-related adverse events in
      patients receiving intravenous ferric carboxymaltose was generally similar to
      that in patients receiving oral ferrous sulfate. In general, rash and local
      injection-site reactions were more common with ferric carboxymaltose, whereas
      gastrointestinal adverse events were more frequent with ferrous sulfate. In
      patients with chronic kidney disease undergoing haemodialysis, a lower proportion
      of ferric carboxymaltose than iron sucrose recipients experienced at least one
      drug-related adverse event.

PMID- 19405555
TI  - Net transport due to noise-induced internal reciprocating motion.
AB  - We consider a system of two coupled Brownian particles fluctuating between two
      states. The fluctuations are produced by both equilibrium thermal and external
      nonthermal noise, the transition rates depending on the interparticle distance.
      An externally induced modulation of the transition rates acts on the internal
      degree of freedom (the interparticle distance) and generates reciprocating motion
      along this coordinate. The system moves unidirectionally due to rectification of
      the internal motion by asymmetric friction fluctuations and thus operates as a
      dimeric motor that converts input energy into net movement. The properties of the
      motor are primarily determined by the properties of the reciprocating engine,
      represented by the interparticle distance dynamics. Two main mechanisms are
      recognized by which the engine operates: energetic and informational. In the
      physically important cases where only one of the motion-inducing mechanisms is
      operative, exact solutions can be found for the model with linearly coupled
      particles. We focus on the informational mechanism, in which thermal noise is
      involved as a vital component and the reciprocating velocity exhibits a rich
      behavior as a function of the model parameters. An efficient rectification method
      for the reciprocating motion is also discussed.

PMID- 19405556
TI  - Coverage of dynamic correlation effects by density functional theory functionals:
      density-based analysis for neon.
AB  - The problem of linking the dynamic electron correlation effects defined in
      traditional ab initio methods [or wave function theories (WFTs)] with the
      structure of the individual density functional theory (DFT) exchange and
      correlation functionals has been analyzed for the Ne atom, for which nondynamic
      correlation effects play a negligible role. A density-based approach directly
      hinged on difference radial-density (DRD) distributions defined with respect the
      Hartree-Fock radial density has been employed for analyzing the impact of dynamic
      correlation effects on the density. Attention has been paid to the elimination of
      basis-set incompleteness errors. The DRD distributions calculated by several ab
      initio methods have been compared to their DFT counterparts generated for
      representatives of several generations of broadly used exchange-correlation
      functionals and for the recently developed orbital-dependent OEP2 exchange
      correlation functional [Bartlett et al., J. Chem. Phys. 122, 034104 (2005)]. For
      the local, generalized-gradient, and hybrid functionals it has been found that
      the dynamic correlation effects are to a large extend accounted for by densities
      resulting from exchange-only calculations. Additional calculations with self
      interaction corrected exchange potentials indicate that this finding cannot be
      explained as an artifact caused by the self-interaction error. It has been
      demonstrated that the VWN5 and LYP correlation functionals do not represent any
      substantial dynamical correlation effects on the electron density, whereas these
      effects are well represented by the orbital-dependent OEP2 correlation
      functional. Critical comparison of the present results with their counterparts
      reported in literature has been made. Some attention has been paid to
      demonstrating the differences between the energy- and density-based perspectives.
      They indicate the usefulness of density-based criteria for developing new
      exchange-correlation functionals.

PMID- 19405550
TI  - Community-associated meticillin-resistant Staphylococcus aureus infections:
      epidemiology, recognition and management.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) is an important cause of
      infection, particularly in hospitalized patients and those with significant
      healthcare exposure. In recent years, epidemic community-associated MRSA (CA
      MRSA) infections occurring in patients without healthcare risk factors have
      become more frequent. The most common manifestation of CA-MRSA infection is skin
      and soft tissue infection, although necrotizing pneumonia, sepsis and
      osteoarticular infections can occur. CA-MRSA strains have become endemic in many
      communities and are genetically distinct from previously identified MRSA strains.
      CA-MRSA may be more capable colonizers of humans and more virulent than other S.
      aureus strains. Specific mechanisms of pathogenicity have not been elucidated,
      but several factors have been proposed as responsible for the virulence of CA
      MRSA, including the Panton-Valentine leukocidin, phenol-soluble modulins and type
      I arginine catabolic mobile element. The movement of CA-MRSA strains into the
      nosocomial setting limits the utility of using clinical risk factors alone to
      designate community- or healthcare-associated status. Identification of unique
      genetic characteristics and genotyping are valuable tools for MRSA
      epidemiological studies. Although the optimum pharmacological therapy for CA-MRSA
      infections has not been determined, many CA-MRSA strains remain broadly
      susceptible to several non-beta-lactam antibacterial agents. Empirical
      antibacterial therapy should include an MRSA-active agent, particularly in areas
      where CA-MRSA is endemic.

PMID- 19405557
TI  - An efficient generalized polyelectron population analysis in orbital spaces: the
      hole-expansion methodology.
AB  - We present relations leading to an efficient generalized population analysis in
      orbital spaces of usual delocalized molecular orbital wave functions. Besides the
      calculation of the diagonal elements of the reduced density matrices of any
      order, one can also calculate efficiently the probabilities (or, in general, the
      weights) of various occupation schemes of local electronic structures, by using
      generalized density operators referring to both electrons and electron holes.
      Within this population analysis, correlated molecular orbital wave functions can
      be used, and there are no restrictions to the number of the analyzed electrons
      and electron holes. It is based on the hole-expansion methodology, according to
      which a given electronic population is expanded in terms involving only electron
      holes, which as shown, can be calculated very efficiently; usual difficulties
      arising from the necessity to handle extremely large local determinantal basis
      sets are avoided, without introducing approximations. Although an emphasis is
      given for populations in the basis of orthogonal orbital spaces (providing
      probabilities), the case of nonorthogonal ones is also considered in order to
      show the connection of the generalized populations and the traditional weights
      obtained from valence-bond wave functions. Physically meaningful populations can
      be obtained by using natural orbitals, such as the natural atomic orbitals (NAOs)
      (orthogonal orbitals) or the pre-NAO's (nonorthogonal orbitals); numerical
      applications for pyrrole molecule are presented in the basis of these natural
      orbitals.

PMID- 19405558
TI  - Optimal sampling efficiency in Monte Carlo simulation with an approximate
      potential.
AB  - Building on the work of Iftimie et al. [J. Chem. Phys. 113, 4852 (2000)] and Gelb
      [J. Chem. Phys. 118, 7747 (2003)], Boltzmann sampling of an approximate potential
      (the "reference" system) is used to build a Markov chain in the isothermal
      isobaric ensemble. At the end points of the chain, the energy is evaluated at a
      more accurate level (the "full" system) and a composite move encompassing all of
      the intervening steps is accepted on the basis of a modified Metropolis
      criterion. For reference system chains of sufficient length, consecutive full
      energies are statistically decorrelated and thus far fewer are required to build
      ensemble averages with a given variance. Without modifying the original
      algorithm, however, the maximum reference chain length is too short to
      decorrelate full configurations without dramatically lowering the acceptance
      probability of the composite move. This difficulty stems from the fact that the
      reference and full potentials sample different statistical distributions. By
      manipulating the thermodynamic variables characterizing the reference system
      (pressure and temperature, in this case), we maximize the average acceptance
      probability of composite moves, lengthening significantly the random walk between
      consecutive full energy evaluations. In this manner, the number of full energy
      evaluations needed to precisely characterize equilibrium properties is
      dramatically reduced. The method is applied to a model fluid, but implications
      for sampling high-dimensional systems with ab initio or density functional theory
      potentials are discussed.

PMID- 19405559
TI  - Bottlenecks to vibrational energy flow in carbonyl sulfide: structures and
      mechanisms.
AB  - Finding the causes for the nonstatistical vibrational energy relaxation in the
      planar carbonyl sulfide (OCS) molecule is a longstanding problem in chemical
      physics: Not only is the relaxation incomplete long past the predicted
      statistical relaxation time but it also consists of a sequence of abrupt
      transitions between long-lived regions of localized energy modes. We report on
      the phase space bottlenecks responsible for this slow and uneven vibrational
      energy flow in this Hamiltonian system with three degrees of freedom. They belong
      to a particular class of two-dimensional invariant tori which are organized
      around elliptic periodic orbits. We relate the trapping and transition mechanisms
      with the linear stability of these structures.

PMID- 19405560
TI  - Approximated electron repulsion integrals: Cholesky decomposition versus
      resolution of the identity methods.
AB  - We compare two procedures to gain efficiency by approximating two-electron
      integrals in molecular electronic structure calculations. The first one is based
      on a Cholesky decomposition (CD) of two-electron integrals, the second one on the
      use of preoptimized auxiliary or fitting basis sets employed in a "resolution of
      the identity" (RI) technique. We present and test auxiliary bases for
      approximating the Coulomb term, which further improves accuracy over previously
      proposed fitting bases. It is shown that RI methods lead to insignificant errors
      only, which are partly comparable to or even better than that of CD treatments;
      but RI procedures are superior in speed. CD methods have certain advantages,
      however, particularly for extended basis sets.

PMID- 19405561
TI  - Dissociation aided and side chain sampling enhanced Hamiltonian replica exchange.
AB  - A new application of Hamiltonian replica exchange method is suggested: The
      potential energy function is adjusted in such a way that repulsive forces between
      atoms of solute are reinforced. This dissociation action helps the system to
      escape from the local minima on the free energy landscape. Compared with other
      Hamiltonian replica exchange methods in which the potential energy between solute
      atoms and between solute and solvent atoms was reduced, and compared with the
      temperature replica exchange method, the new scheme displays superior ability to
      overcome large free energy barrier in a model system. For protein simulation, the
      side chain conformation sampling turns out to be an issue and an enhancement
      method is introduced. Combining the dissociation aided method with the specific
      side chain sampling technique is proven to be a help to explore the complex
      energy landscape of protein, which is demonstrated by three independent ab initio
      folding simulations on the trpzip2 peptide.

PMID- 19405562
TI  - Energy-consistent pseudopotentials and correlation consistent basis sets for the
      5d elements Hf-Pt.
AB  - New relativistic energy-consistent pseudopotentials have been generated for the
      5d transition metals Hf-Pt. The adjustment was done in numerical two-component
      multiconfiguration Hartree-Fock calculations, using atomic valence-energy spectra
      from four-component multiconfiguration Dirac-Hartree-Fock calculations as
      reference data. The resulting two-component pseudopotentials replace the
      [Kr]4d(10)4f(14) cores of the 5d transition metals and can easily be split into a
      scalar-relativistic and a spin-orbit part. They reproduce the all-electron
      reference energy data with deviations of approximately 0.01 eV for
      configurational averages and approximately 0.05 eV for individual relativistic
      states. Full series of correlation consistent basis sets from double to quintuple
      zeta have also been developed in this work for use with the new pseudopotentials.
      In addition, all-electron triple-zeta quality correlation consistent basis sets
      are also reported in order to provide calibration for the pseudopotential
      treatment. The accuracy of both the pseudopotentials and basis sets are assessed
      in extensive coupled cluster benchmark calculations of atomic ionization
      potentials, electron affinities, and selected excitation energies of all the 5d
      metal atoms, including the effects of spin-orbit coupling.

PMID- 19405563
TI  - Open-shell molecular electronic states from the parametric two-electron reduced
      density-matrix method.
AB  - The parametric variational two-electron reduced-density-matrix (2-RDM) method,
      developed from an analysis of positivity (N-representability) constraints on the
      2-RDM, is extended to treat both closed- and open-shell molecules in singlet,
      doublet, and triplet spin states. The parametric 2-RDM method can be viewed as
      using N-representability conditions to modify the 2-RDM from a configuration
      interaction singles-doubles wave function to make the energy size extensive while
      keeping the 2-RDM approximately N-representable [J. Kollmar, Chem. Phys. 125,
      084108 (2006); A. E. DePrince and D. A. Mazziotti, Phys. Rev. A 76, 049903
      (2007)]. Vertical excitation energies between triplet and singlet states are
      computed in a polarized valence triple-zeta basis set. In comparison to
      traditional single-reference wave function methods, the parametric 2-RDM method
      recovers a larger percentage of the multireference correlation in the singlet
      excited states, which improves the accuracy of the vertical excitation energies.
      Furthermore, we show that molecular geometry optimization within the parametric 2
      RDM method can be efficiently performed through a Hellmann-Feynman-like relation
      for the energy gradient with respect to nuclear coordinates. Both the open-shell
      extension and the energy-gradient relation are applied to computing relative
      energies and barrier heights for the isomerization reaction HCN(+)<-->HNC(+). The
      computed 2-RDMs very nearly satisfy well known, necessary N-representability
      conditions.

PMID- 19405564
TI  - Intracule functional models. IV. Basis set effects.
AB  - We have calculated position and dot intracules for a series of atomic and
      molecular systems, starting from an unrestricted Hartree-Fock wave function,
      expanded using the STO-3G, 6-31G, 6-311G, 6-311++G, 6-311++G(d,p), 6
      311++G(3d,3p), and 6-311++G(3df,3pd) basis sets as well as the nonpolarized part
      of Dunning's cc-pV5Z basis. We find that the basis set effects on the intracules
      are small and that correlation energies from the dot intracule ansatz are
      remarkably insensitive to the basis set quality. Mean absolute errors in
      correlation energies across the G1 data set agree to within 2 mE(h) for all basis
      sets tested.

PMID- 19405566
TI  - Exploring the capabilities of quantum optimal dynamic discrimination.
AB  - Optimal dynamic discrimination (ODD) uses closed-loop learning control techniques
      to discriminate between similar quantum systems. ODD achieves discrimination by
      employing a shaped control (laser) pulse to simultaneously exploit the unique
      quantum dynamics particular to each system, even when they are quite similar. In
      this work, ODD is viewed in the context of multiobjective optimization, where the
      competing objectives are the degree of similarity of the quantum systems and the
      level of controlled discrimination that can be achieved. To facilitate this
      study, the D-MORPH gradient algorithm is extended to handle multiple quantum
      systems and multiple objectives. This work explores the trade-off between laser
      resources (e.g., the length of the pulse, fluence, etc.) and ODD's ability to
      discriminate between similar systems. A mechanism analysis is performed to
      identify the dominant pathways utilized to achieve discrimination between similar
      systems.

PMID- 19405567
TI  - Nonadiabatic corrections to rovibrational levels of H2.
AB  - The leading nonadiabatic corrections to rovibrational levels of a diatomic
      molecule are expressed in terms of three functions of internuclear distance:
      corrections to the adiabatic potential, the effective nuclear mass, and the
      effective moment of inertia. The resulting radial Schrodinger equation for
      nuclear motion is solved numerically yielding accurate nonadiabatic energies for
      all rovibrational levels of the H(2) molecule. Results for states with J < or =
      10 are in excellent agreement with previous calculations by Wolniewicz, and for
      states with J > 10 are new.

PMID- 19405565
TI  - Calculating solution redox free energies with ab initio quantum
      mechanical/molecular mechanical minimum free energy path method.
AB  - A quantum mechanical/molecular mechanical minimum free energy path (QM/MM-MFEP)
      method was developed to calculate the redox free energies of large systems in
      solution with greatly enhanced efficiency for conformation sampling. The QM/MM
      MFEP method describes the thermodynamics of a system on the potential of mean
      force surface of the solute degrees of freedom. The molecular dynamics (MD)
      sampling is only carried out with the QM subsystem fixed. It thus avoids "on-the
      fly" QM calculations and thus overcomes the high computational cost in the direct
      QM/MM MD sampling. In the applications to two metal complexes in aqueous
      solution, the new QM/MM-MFEP method yielded redox free energies in good agreement
      with those calculated from the direct QM/MM MD method. Two larger biologically
      important redox molecules, lumichrome and riboflavin, were further investigated
      to demonstrate the efficiency of the method. The enhanced efficiency and
      uncompromised accuracy are especially significant for biochemical systems. The
      QM/MM-MFEP method thus provides an efficient approach to free energy simulation
      of complex electron transfer reactions.

PMID- 19405568
TI  - Recovering four-component solutions by the inverse transformation of the infinite
      order two-component wave functions.
AB  - The two-component Hamiltonian of the infinite-order two-component (IOTC) theory
      is obtained by a unitary block-diagonalizing transformation of the Dirac
      Hamiltonian. Once the IOTC spin orbitals are calculated, they can be back
      transformed into four-component solutions. The transformed four component
      solutions are then used to evaluate different moments of the electron density
      distribution. This formally exact method may, however, suffer from certain
      approximations involved in its numerical implementation. As shown by the present
      study, with sufficiently large basis set of Gaussian functions, the Dirac values
      of these moments are fully recovered in spite of using the approximate identity
      resolution into eigenvectors of the p(2) operator.

PMID- 19405569
TI  - Approximating quantum many-body intermolecular interactions in molecular clusters
      using classical polarizable force fields.
AB  - Many-body intermolecular interaction expansions provide a promising avenue for
      the efficient quantum mechanical treatment of molecular clusters and condensed
      phase systems, but the computationally expensive three-body and higher terms are
      often nontrivial. When polar molecules are involved, these many-body terms are
      typically dominated by electrostatic induction effects, which can be approximated
      relatively easily. We demonstrate an accurate and inexpensive hybrid
      quantum/classical model in which one- and two-body interactions are computed
      quantum mechanically, while the many-body induction effects are approximated with
      a simple classical polarizable force field. Whereas typical hybrid
      quantum/classical models partition a system spatially into distinct quantum and
      classical regions, the model demonstrated here partitions based on the order in
      the many-body interaction series. This enables a spatially homogeneous treatment
      of the entire system, which could prove advantageous in studying a wide range of
      condensed-phase molecular systems.

PMID- 19405570
TI  - Analysis and classification of symmetry breaking in linear ABA-type triatomics.
AB  - The symmetry of the nuclear framework of polyatomic molecules is qualitatively
      lowered by small changes in their geometry. This may lead to a dramatic change in
      the nature of their Hartree-Fock (HF) solutions and to a singular behavior of the
      corresponding potential energy surfaces (PESs), which may persist even at the
      correlated level if based on these HF references. We examine a general shape of
      the restricted HF (RHF) and open-shell RHF PESs for the linear triatomic
      molecules of the ABA type in the vicinity of the symmetric D(2h) geometries and
      the role played by the spin-restricted (singlet or doublet) stability of the
      corresponding HF solutions. This enabled us to classify the character of these
      surfaces into three basic types depending on the nature of the cut of the PES
      along the asymmetric stretching mode coordinate. We also examine the implications
      of the type of these nodes on the PES obtained at the post-HF correlated CCSD(T)
      level as well as on the determination of the vibrational frequencies for both the
      symmetric and asymmetric stretching modes. When using either the numerical
      differentiation of the PES or the solution of the Schrodinger equation for the
      nuclear motion for this purpose, it is shown that either method yields very good
      results for the symmetric mode frequencies, while the former approach may yield
      highly erroneous values for the asymmetric mode frequencies depending on the type
      of the HF PES at the equilibrium geometry in which case the latter approach still
      provides us with reasonably good results.

PMID- 19405571
TI  - Bubble merging in breathing DNA as a vicious walker problem in opposite
      potentials.
AB  - We investigate the coalescence of two DNA bubbles initially located at weak
      domains and separated by a more stable barrier region in a designed construct of
      double-stranded DNA. In a continuum Fokker-Planck approach, the characteristic
      time for bubble coalescence and the corresponding distribution are derived, as
      well as the distribution of coalescence positions along the barrier. Below the
      melting temperature, we find a Kramers-type barrier crossing behavior, while at
      high temperatures, the bubble corners perform drift diffusion toward coalescence.
      In the calculations, we map the bubble dynamics on the problem of two vicious
      walkers in opposite potentials. We also present a discrete master equation
      approach to the bubble coalescence problem. Numerical evaluation and stochastic
      simulation of the master equation show excellent agreement with the results from
      the continuum approach. Given that the coalesced state is thermodynamically
      stabilized against a state where only one or a few of the base pairs of the
      barrier region are re-established, it appears likely that this type of setup
      could be useful for the quantitative investigation of thermodynamic DNA stability
      data as well as the rate constants involved in the unzipping and zipping dynamics
      of DNA in single molecule fluorescence experiments.

PMID- 19405572
TI  - Microcanonical rates, gap times, and phase space dividing surfaces.
AB  - The general approach to classical unimolecular reaction rates due to Thiele is
      revisited in light of recent advances in the phase space formulation of
      transition state theory for multidimensional systems. Key concepts, such as the
      phase space dividing surface separating reactants from products, the average gap
      time, and the volume of phase space associated with reactive trajectories, are
      both rigorously defined and readily computed within the phase space approach. We
      analyze in detail the gap time distribution and associated reactant lifetime
      distribution for the isomerization reaction HCN <==> CNH, previously studied
      using the methods of phase space transition state theory. Both algebraic (power
      law) and exponential decay regimes have been identified. Statistical estimates of
      the isomerization rate are compared with the numerically determined decay rate.
      Correcting the RRKM estimate to account for the measure of the reactant phase
      space region occupied by trapped trajectories results in a drastic overestimate
      of the isomerization rate. Compensating but as yet not fully understood trapping
      mechanisms in the reactant region serve to slow the escape rate sufficiently that
      the uncorrected RRKM estimate turns out to be reasonably accurate, at least at
      the particular energy studied. Examination of the decay properties of
      subensembles of trajectories that exit the HCN well through either of two
      available symmetry related product channels shows that the complete trajectory
      ensemble effectively attains the full symmetry of the system phase space on a
      short time scale t approximately < 0.5 ps, after which the product branching
      ratio is 1:1, the "statistical" value. At intermediate times, this statistical
      product ratio is accompanied by nonexponential (nonstatistical) decay. We point
      out close parallels between the dynamical behavior inferred from the gap time
      distribution for HCN and nonstatistical behavior recently identified in reactions
      of some organic molecules.

PMID- 19405573
TI  - Fine structure and hyperfine perturbations in the pure rotational spectrum of the
      VCl radical in its X 5Delta(r) state.
AB  - The pure rotational spectrum of the VCl radical in its (5)Delta(r) ground state
      has been recorded in the range 236-417 GHz using millimeter/submillimeter direct
      absorption techniques. This species was created in an ac discharge of VCl(4) and
      argon. Ten rotational transitions of V(35)Cl were measured in all five Omega
      ladders; an additional nine transitions of the Omega=1 spin state were recorded
      in order to evaluate the (51)V hyperfine structure. Hyperfine interactions
      associated with the (35)Cl nucleus were not resolved, consistent with the ionic
      structure of the molecule. Because of extensive perturbations caused by the low
      lying A (5)Pi(r) excited state, the rotational spectrum of the ground state has
      been found to be quite irregular. The four lowest Omega ladders exhibit unusually
      large lambda-doubling interactions, with the Omega=1 component showing the
      largest splitting, over 2 GHz in magnitude. The Omega=1 transitions are also
      shifted to higher frequency relative to the other spin components. In addition,
      the hyperfine structure varies widely between the Omega ladders, and an avoided
      crossing is observed in two transitions of both the Omega=1e and 2e components.
      The data have been analyzed with a case (c) Hamiltonian, and effective
      rotational, lambda-doubling, and hyperfine constants have been determined for
      V(35)Cl. Higher-order parity-dependent magnetic hyperfine terms d(Delta2) and
      d(Delta3) were required in the analysis, derived from perturbation theory, in
      addition to the usual d(Delta) parameter. The local perturbations evident in
      these spectra indicate that the A (5)Pi(r) excited state lies within the spin
      orbit manifold of the ground state, well below the predicted value of 517 cm(-1).
      Mixing of the A (5)Pi(r) and X (5)Delta(r) states apparently causes both local
      and global perturbations in the ground state spectrum.

PMID- 19405574
TI  - H3(+) + H2 isotopic system at low temperatures: microcanonical model and
      experimental study.
AB  - State-to-state thermal rate coefficients for reactions of all H(3)(+) + H(2)
      isotopic variants are derived and compared to new experimental data. The
      theoretical data are also sought for astrochemical modeling of cold environments
      (<50 K). The rates are calculated on the basis of a microcanonical approach using
      the Langevin model and the conservation laws of mass, energy, angular momentum,
      and nuclear spin. Full scrambling of all five nuclei during the collision is
      assumed for the calculations and alternatively partial dynamical restrictions are
      considered. The ergodic principle of the collision is employed in two limiting
      cases, neglecting (weak ergodic limit) or accounting for explicit degeneracies of
      the reaction mechanisms (strong ergodic limit). The resulting sets of rate
      coefficients are shown to be consistent with the detailed balance and
      thermodynamical equilibrium constants. Rate coefficients, k(T), for the
      deuteration chain of H(3)(+) with HD as well as H(2)D(+)/H(3)(+) equilibrium
      ratios have been measured in a variable temperature 22-pole ion trap. In
      particular, the D(2)H(+) + HD --> D(3)(+) + H(2) rate coefficient indicates a
      change in reaction mechanism when going to higher temperatures. The good overall
      agreement between experiment and theory encourages the use of the theoretical
      predictions for astrophysical modeling.

PMID- 19405575
TI  - Pure rotational spectra of the CCCF radical.
AB  - Pure rotational transitions of a new carbon-chain radical CCCF in a supersonic
      jet have been observed for the first time using a Fourier-transform microwave
      spectrometer with a pulsed-discharge nozzle. The radical was produced by a pulsed
      electric discharge in a C(2)H(2) and CF(4) mixture diluted to 0.1% and 0.1% with
      Ne, respectively. Rotational transitions with spin and hyperfine splittings have
      been observed in the region from 9.1 GHz for N(K(a)K(c)) = 1(01)-0(00) to 27.3
      GHz for N(K(a)K(c)) = 3(03)-2(02). The rotational constant, the spin-rotation
      interaction constant, and the hyperfine coupling constants due to the F nucleus
      have been precisely determined from the least-squares analysis, yielding B =
      4555.8043(44), gamma(eff) = -7.105(16), b(F,eff) = 368(19), and c(eff) = 
      284.832(61) MHz. The determined molecular constants were compared with those
      obtained from high-level ab initio calculations and concluded that the CCCF
      radical has a bent ground state X(2)A(').

PMID- 19405576
TI  - Structures and reactions of methanol molecules on cobalt cluster ions studied by
      infrared photodissociation spectroscopy.
AB  - Structures of methanol molecules chemisorbed on cobalt cluster ions, Co(n)(+)
      (n=2-6), were investigated by infrared photodissociation (IR-PD) spectroscopy in
      the wavenumber range of 3400-4000 cm(-1). All the IR-PD spectra measured exhibit
      an intense peak in the region of the OH stretching vibration. In the IR-PD
      spectra of Co(2)(+)(CH(3)OH)(2,3) and Co(3)(+)(CH(3)OH)(3), weak peaks were
      observed additionally in the vicinity of 3000 cm(-1), being assignable to the CH
      stretching vibration. The comparison of the experimental results with the
      calculated ones leads us to conclude that (1) molecularly chemisorbed species,
      Co(n)(+)(CH(3)OH)(m) (m=1-3), and dissociatively chemisorbed species,
      Co(n)(+)(CH(3)OH)(m-1)(CH(3))(OH), are dominant and (2) the methanol
      dehydrogenation proceeds via an intermediate, Co(n)(+)(CH(3))(OH).

PMID- 19405577
TI  - Nitrous oxide dimer: an ab initio coupled-cluster study of isomers,
      interconversions, and infrared fundamental bands, and experimental observation of
      a new fundamental for the polar isomer.
AB  - Improved quantum chemistry (coupled-cluster) results are presented for
      spectroscopic parameters and the potential energy surface for the N(2)O dimer.
      The calculations produce three isomer structures, of which the two lowest energy
      forms are those observed experimentally: a nonpolar C(2h)-symmetry planar slipped
      antiparallel geometry (with inward-located O atoms) and a higher-energy polar
      C(s)-symmetry planar slipped-parallel geometry. Harmonic vibrational frequencies
      and infrared intensities for these isomers are calculated. The low-frequency
      intermolecular vibrational mode predictions should be useful for future
      spectroscopic searches, and there is good agreement in the one case where an
      experimental value is available. The frequency shifts for the high-frequency
      intramolecular stretching vibrations, relative to the monomer, were calculated
      and used to help locate a new infrared band of the polar isomer, which
      corresponds to the weaker out-of-phase combination of the nu(1) antisymmetric
      stretch of the individual monomers. The new band was observed in the region of
      the monomer nu(1) fundamental for both ((14)N(2)O)(2) and ((15)N(2)O)(2) using a
      tunable infrared diode laser to probe a pulsed supersonic jet expansion, and
      results are presented.

PMID- 19405578
TI  - Theoretical study of proton tunneling in the excited state of tropolone.
AB  - Ab initio CIS/6-311++G(d,p) calculations of geometry and vibrational frequencies
      have been carried out in the A state of tropolone. The grids of potential energy
      surfaces along the coordinates of high frequency tunneling vibration and the low
      frequency coupled vibration have been calculated. Two-dimensional model
      potentials, formed from symmetric mode coupling potential and squeezed double
      well potential, have been fitted to the calculated potential energy surfaces and
      used to analyze proton dynamics. The tunneling splittings for different
      vibrationally excited states have been calculated and compared with the available
      experimental data. The model potential energy surfaces, based on the CIS/6
      311++G(d,p) calculations, give good estimation of the tunneling energy splittings
      in the vibrationally ground and excited states of tropolone and explain monotonic
      decrease in tunneling splittings with the excitation of low-frequency out-of
      plane modes and increase in the tunneling splittings with the excitation of low
      frequency planar modes.

PMID- 19405579
TI  - R-matrix calculation of low-energy electron collisions with uracil.
AB  - R-matrix calculations on electron-uracil collisions are presented within the
      static exchange, static exchange plus polarization, and close-coupling
      approximations. Particularly as input for the close-coupling calculations, a
      series of target calculations is performed which considers low-lying singlet and
      triplet excited states of the uracil target. The scattering calculations find
      three low-lying shape resonances of (2)A(") symmetry and three higher-energy
      Feshbach resonances of (2)A(') symmetry. In both symmetries the precise resonance
      parameters are found to be sensitive to the treatment of polarization effects
      employed. Cross sections are presented for both elastic scattering and electronic
      excitation. Comparisons are made with energy-dependent, differential cross
      section measurements at 90 degrees angle and good agreement is found for
      scattering energies above 0.5 eV.

PMID- 19405580
TI  - Excited states of Nb3N2 and Nb3C2: density functional theory, CASSCF, and MRCI
      studies.
AB  - Complete active space self-consistent field (CASSCF) and multireference
      configuration interaction (MRCI) methods are used to investigate the Nb(3)N(2)
      and Nb(3)C(2) clusters in order to determine the agreement between multireference
      methods, density functional theory (DFT), and experiment. These two clusters are
      ideal candidates to study as the known spectroscopy can serve to validate the
      computational results, yet there is still room for the calculations to inform
      further spectroscopic experiments. We find that the MRCI leading configuration
      for each of the ground states is in agreement with that predicted by DFT but only
      accounts for up to 70% of the total configuration. CASSCF and DFT geometries are
      also in general agreement. Transition energies between the neutral and cationic
      manifolds are found to be poorly predicted by MRCI relative to the
      computationally cheap DFT method. For Nb(3)C(2) we find that a higher energy
      isomer may have an electronic transition in the spectral vicinity as the lowest
      energy isomer.

PMID- 19405581
TI  - The electronic spectrum of the fluoroborane free radical. I. Theoretical
      calculation of the vibronic energy levels of the ground and first excited
      electronic states.
AB  - The fluoroborane (HBF) free radical has a large vibronic interaction which splits
      the orbitally degenerate (2)Pi state in the linear configuration into two
      separate electronic states, one strongly bent and one linear. The observed
      vibrational structure of the electronic transition between the Renner-Teller pair
      of states is very complex. As an aid to understanding the spectrum, the vibronic
      energy levels of the ground and first excited states have been calculated from
      high-level ab initio potential energy surfaces using a variational method. The
      vibrational frequencies and anharmonicities have been derived from these energy
      levels and the boron and hydrogen isotope shifts have been predicted. Although
      the ground state energy levels are for the most part well behaved, the excited
      state levels show substantial Renner-Teller mixing with nearby ground vibrational
      states. The calculations in the present work have been successfully used in the
      companion paper to make vibrational assignments of the laser-induced fluorescence
      spectra of HBF and DBF.

PMID- 19405582
TI  - The electronic spectrum of the fluoroborane free radical. II. Analysis of laser
      induced fluorescence and single vibronic level emission spectra.
AB  - Subsequent to our spectroscopic detection of the HBX (X=F, Cl, Br) free radicals
      (S.-G. He, F. X. Sunahori, and D. J. Clouthier, J. Am. Chem. Soc. 127, 10814
      (2005)), the electronic spectrum of the A (2)A(")Pi-X (2)A(') system of the
      fluoroborane (HBF) radical in the 600-745 nm region has been studied in detail
      using the pulsed discharge jet technique. The band system involves a linear-bent
      transition between the two Renner-Teller components of what would be a (2)Pi
      state at linearity. Using the results of our theoretical study of the ground and
      excited state vibrational energy levels and (11)B-(10)B isotope shifts (see the
      companion paper), the vibrational quantum numbers of the bands in the laser
      induced fluorescence (LIF) spectra have been assigned. Rotational and vibrational
      analyses of the LIF and wavelength resolved emission spectra have been carried
      out, from which the linear excited state and the bent ground state equilibrium
      configurations have been confirmed. The ground state molecular geometry of HBF
      has been determined as r(0)(BH)=1.214(2) A, r(0)(BF)=1.303 4(5) A, and
      theta=120.7(1) degrees. Based on high-level ab initio calculations and symmetry
      considerations, predissociation of the excited state into H((2)S)+BF((1)Sigma(+))
      on the ground state potential energy surface is identified as the cause of the
      breaking off of fluorescence in the LIF spectra.

PMID- 19405583
TI  - Photoionization efficiency spectroscopy and density functional theory
      investigations of RhHo2O(n) (n = 0-2) clusters.
AB  - The experimental and theoretical adiabatic ionization energies (IEs) of the
      rhodium-holmium bimetallic clusters RhHo(2)O(n) (n=0-2) have been determined
      using photoionization efficiency spectroscopy and density functional theory (DFT)
      calculations. Both sets of data show the IE of RhHo(2)O to be significantly lower
      than the values for RhHo(2) and RhHo(2)O(2), which are found to be similar. This
      indicates that there are significant changes in electronic properties upon
      sequential addition of oxygen atoms to RhHo(2). The DFT investigations show that
      the lowest energy neutral structures are a C(2v) triangle for RhHo(2), a C(2v)
      planar structure for RhHo(2)O where the O atom is doubly bridged to the Ho-Ho
      bond, and a C(2v) nonplanar structure for RhHo(2)O(2), where the O(2) is
      dissociative and each O atom is doubly bridged to the Ho-Ho bond in the cluster
      above and below the RhHo(2) trimer plane. Good correlation between the
      experimental and computational IE data imply that the lowest energy neutral
      structures calculated are the most likely isomers ionized in the molecular beam.
      In particular, the theoretical adiabatic IE for the dissociative RhHo(2)O(2)
      structure is found to compare better with the experimentally determined value
      than the corresponding lowest energy O(2) associative structure.

PMID- 19405584
TI  - Site-dependent photodissociation of vibrationally excited CD3NH2.
AB  - The N-H and C-D bond fission in partially deuterated methylamine, CD(3)NH(2), has
      been investigated using vibrationally mediated photodissociation. Jet-cooled
      action spectra and Doppler profiles of the H and D photofragments were monitored
      following approximately 243.1 nm photodissociation of the parent pre-excited to
      two, three or four N-H stretch quanta. The action spectra were analyzed in terms
      of simplified local mode/normal mode (LM/NM) and NM models, allowing band
      assignment and determination of the strong resonances involved in the coupling.
      The Doppler profiles show that the released H and D photofragments have low
      translational energy content and that the H is the dominant product, although its
      yield decreases as higher pre-excited N-H vibrational states are dissociated. The
      dynamics of the site-dependent bond fission in CD(3)NH(2) is discussed.

PMID- 19405585
TI  - Stable T2Si(n) (T = Fe, Co, Ni, 1 < or = n < or = 8) cluster motifs.
AB  - First principles studies on the geometry, electronic structure, and magnetic
      properties of neutral and anionic Fe(2)Si(n), Co(2)Si(n), and Ni(2)Si(n) (1 < or
      = n < or = 8) clusters have been carried out within a gradient corrected density
      functional framework. It is shown that these clusters display a variety of
      magnetic species with varying magnetic moment and different magnetic coupling
      between the two transition metal atoms. While Fe(2)Si(n) clusters are mostly
      ferromagnetic with large moments, Ni(2)Si(n) clusters are mostly nonmagnetic. Our
      studies of the variation of the binding energy upon addition of successive Si
      atoms and the gap between the highest occupied molecular orbital and the lowest
      unoccupied molecular orbital indicate that many of the motifs are quite stable
      and could be suitable as building blocks for generating magnetic cluster
      assembled materials. The studies also reveal motifs that could be used in
      molecular electronic devices to generate spin polarized currents or large
      magnetoresistance.

PMID- 19405586
TI  - Roto-translational Raman spectra of pairs of hydrogen molecules from first
      principles.
AB  - We calculate the collision-induced, roto-translational, polarized, and
      depolarized Raman spectra of pairs of H(2) molecules. The Schrodinger equation of
      H(2)-H(2) scattering in the presence of a weak radiation field is integrated in
      the close-coupled scheme. This permits the accounting for the anisotropy of the
      intermolecular potential energy surface and thereby it includes mixing of
      polarizability components. The static polarizability invariants, trace and
      anisotropy, of two interacting H(2) molecules were obtained elsewhere [Li et al.,
      J. Chem. Phys. 126, 214302 (2007)] from first principles. Here we report the
      associated spherical tensor components which, along with the potential surface,
      are input in the calculation of the supramolecular Raman spectra. Special
      attention is paid to the interferences in the wings of the rotational S(0)(0) and
      S(0)(1) lines of the H(2) molecule. The calculated Raman pair spectra show
      reasonable consistency with existing measurements of the polarized and
      depolarized Raman spectra of pairs of H(2) molecules.

PMID- 19405587
TI  - Tensor cross sections and collisional depolarization of OH(X 2Pi) in collisions
      with helium.
AB  - Tensor cross sections for collisions of OH(X (2)Pi) with helium are computed
      using accurate ab initio potential energy surfaces computed by Lee et al. We use
      these cross sections to predict rate constants for collisional depolarization of
      specific rotational fine-structure levels of OH(X (2)Pi) in collisions with
      helium. Good agreement is found with the results of the two-color polarization
      spectroscopy experiments of Paterson et al. [J. Chem. Phys. 129, 074304 (2008)].
      By examination of partial cross sections, the range of impact parameters at which
      collisional depolarization occurs is shown to be similar to that for rotationally
      inelastic collisions.

PMID- 19405588
TI  - Structural properties of glucose-dimethylsulfoxide solutions probed by Raman
      spectroscopy.
AB  - Raman spectroscopy was employed to achieve a molecular level description of
      solvation properties in glucose-dimethylsulfoxide (DMSO) solutions. The analysis
      of Raman spectra confirms the importance of the dipole-dipole interaction in
      determining structural properties of pure DMSO; the overall intermolecular
      structure is maintained in the whole 20-75 degrees C temperature range
      investigated. The blueshift of the CH stretching modes observed at higher
      temperatures points out that CH(3)...O contacts contribute to the cohesive energy
      of the DMSO liquid system. The addition of glucose perturbs the intermolecular
      ordering of DMSO owing to the formation of stable solute-solvent hydrogen bonds.
      The average number of OH...OS contacts (3.2+/-0.3) and their corresponding energy
      (approximately 20 kJ/mol) were estimated. Besides, the concentration dependence
      of the CH stretching bands and the behavior of the noncoincidence effect on the
      SO band, suggest that the dipole-dipole and CH(3)...O interactions among DMSO
      molecules are disfavored within the glucose solvation layer. These findings
      contribute to improve our understanding about the microscopic origin of solvent
      properties of DMSO toward more complex biomolecular systems.

PMID- 19405589
TI  - On dynamic heterogeneity in supercooled liquids.
AB  - A simplified molecular theory for the dynamics of liquids near the glass
      transition temperature T(g) is developed and compared with experimental viscosity
      and diffusion behavior. Its basis is the spatial fluctuations of local density, a
      property that depends on isothermal compressibility and thus occurs naturally in
      all liquids at equilibrium. Instantaneous liquid structure is approximated by
      randomly distributed arrays of two domains having either higher or lower density
      than the average. The time dependence of fluctuations is represented by a
      sequence of such structures, each having a lifetime that varies with the
      macroscopic density. The dynamic environment of a molecule within a domain (slow
      or fast) depends on the density of its domain (high or low). Translational
      diffusion and orientational relaxation depend on different averages of the slow
      and fast domain contributions and lead, on approaching T(g), to a progressive
      departure from the Stoke-Einstein relationship. Predictions are made using
      macroscopic viscosity-density relationships within the individual domains. They
      depend only on the choice of domain size, which, according to this formulation,
      is insensitive to temperature. The data for three well-studied nonpolymeric
      liquids were found to be in reasonable accord with NMR assessments of domain
      size.

PMID- 19405590
TI  - Phase-resolved two-dimensional spectroscopy based on collinear n-wave mixing in
      the ultrafast time domain.
AB  - We present a novel approach for femtosecond two-dimensional (2D) spectroscopy in
      the midinfrared combining a collinear beam geometry and phase-resolved detection.
      Two phase-locked pulses of variable time delay tau interact with the sample. The
      transmitted electric fields are measured in real time t by electro-optic
      sampling. 2D spectra are generated by Fourier transforming the signal along the
      two time axes tau and t. In the 2D spectra, nonlinear signals originating from
      different orders n in the electric field are separated. Such decomposition of the
      overall response is demonstrated by mapping the nonlinear response of
      intersubband transitions in GaAs/AlGaAs multiple quantum wells.

PMID- 19405591
TI  - Rotation of methyl radicals in a solid krypton matrix.
AB  - Electron spin resonance (ESR) measurements were carried out to study the rotation
      of methyl radicals (CH(3)) in a solid krypton matrix at 17-31 K temperature
      range. The radicals were produced by dissociating methane by plasma bursts
      generated by a focused 193 nm excimer laser radiation during the krypton gas
      condensation on the substrate. The ESR spectrum exhibits only isotropic features
      at the temperature range examined, and the intensity ratio between the symmetric
      (A) and antisymmetric (E) spin state lines exhibits weaker temperature dependence
      than in a solid argon matrix. However, the general appearance of the methyl
      radical spectrum depends strongly on temperature due to the pronounced
      temperature dependency of the E state linewidths. The rotational energy level
      populations are analyzed based on the static crystal field model, pseudorotating
      cage model, and quantum chemical calculations for an axially symmetric, planar
      rotor. Crystal field strength parameter values of -140 cm(-1) in Ar and -240 cm(
      1) in Kr match most closely the experimentally observed rotational energy level
      shifts from the gas phase value. In the alternative model, considering the
      lattice atom movement in a pseudorotating cage, the effective lowering of the
      rotational constants B and C to 80%-90% leads to similar effects.

PMID- 19405592
TI  - Translational and internal states of hydrogen molecules produced from the
      ultraviolet photodissociation of amorphous solid methanol.
AB  - Translationally and internally hot H(2) molecules are produced from the 157 nm
      photodissociation of amorphous solid methanol at 90 K by two distinct mechanisms:
      exothermic recombination of two H-atom photoproducts bound to the surface and
      unimolecular molecular elimination of H(2) from the photoexcited methanol. The
      vibrationally hot H(2)(v=2-5) products are characterized by high translational
      and rotational temperatures. A third mechanism, the almost thermoneutral
      abstraction of a hydrogen atom from methanol parent molecule by the
      photolytically produced hydrogen atom, yields translationally and rotationally
      cold H(2)(v=0 and 1) products. Comparison with the results of the vacuum
      ultraviolet photolysis of water ice is discussed. Production of translationally
      hot and cold hydrogen atoms is also confirmed.

PMID- 19405593
TI  - Probing chiral solute-water hydrogen bonding networks by chirality transfer
      effects: a vibrational circular dichroism study of glycidol in water.
AB  - Vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of
      (S)-(-)-glycidol were measured in water with a concentration of 6.0M in the 1000
      1750 cm(-1) region. Prominent and complex VCD spectral features were detected at
      the water bending vibrational region. Our experimental results show that water
      molecules can become optically active through hydrogen bonding interactions with
      glycidol molecules. To model the glycidol-water hydrogen bonding network in the
      solution, molecular dynamics simulations using the AMBER9 suite of programs were
      carried out. Altogether, 34 conformers of the small glycidol-(water)(N) clusters
      with N=1, 2, 3, and 4 were considered. Geometry optimizations, harmonic frequency
      calculations, and the VA and VCD intensity predictions of these small glycidol
      water clusters were performed at the B3LYP/6-311++G(d,p) level of theory using
      the GAUSSIAN 03 program package. Strong cooperative hydrogen bonding effects were
      detected in the larger glycidol-(water)(N) clusters. The population weighted VA
      and VCD spectra of each N group of glycidol (water)(N=1,2,3,4) were used to
      produce the simulated VA and VCD spectra, which are in good agreement with the
      experimental VA and VCD spectra. The study shows that all these clusters make
      important contributions to the observed spectra and are the most important
      species in the aqueous solution with complicated equilibriums among them.

PMID- 19405594
TI  - Transport properties of highly asymmetric hard-sphere mixtures.
AB  - The static and dynamic properties of binary mixtures of hard spheres with a
      diameter ratio of sigma(B)/sigma(A)=0.1 and a mass ratio of m(B)/m(A)=0.001 are
      investigated using event driven molecular dynamics. The contact values of the
      pair correlation functions are found to compare favorably with recently proposed
      theoretical expressions. The transport coefficients of the mixture, determined
      from simulation, are compared to the predictions of the revised Enskog theory
      using both a third-order Sonine expansion and direct simulation Monte Carlo.
      Overall, the Enskog theory provides a fairly good description of the simulation
      data, with the exception of systems at the smallest mole fraction of larger
      spheres (x(A)=0.01) examined. A "fines effect" was observed at higher packing
      fractions, where adding smaller spheres to a system of large spheres decreases
      the viscosity of the mixture; this effect is not captured by the Enskog theory.

PMID- 19405595
TI  - Efficient approach to nucleation and growth dynamics: stationary diffusion flux
      model.
AB  - A new model describing the evolution of clusters in the processes of nucleation
      and growth is proposed. The diffusion flux in the nonstationary Fokker-Planck
      equation with an unknown distribution function is approximated by the closed form
      expression containing the steady-state solution of the Zeldovich-Frenkel
      equation. This is justified due to the smallness of induction time of cluster
      formation compared to the time scale observed in experiments. The resulting
      stationary diffusion flux model is valid for all cluster sizes, computationally
      efficient and applicable to various types of cluster formation processes. Its
      application to a nucleation pulse experiment shows an excellent agreement with
      the solution of the set of formally exact Becker-Doring equations.

PMID- 19405597
TI  - Purely absorptive three-dimensional infrared spectroscopy.
AB  - We demonstrate a method to collect purely absorptive three-dimensional (3D) fifth
      order vibrational spectra on the model system CO(2) in H(2)O. The six beam
      interferometer is described, as well as a method to experimentally determine the
      phase of the 3D spectrum. The measured spectra agree very well with simulations
      of the data based on the cumulant expansion. There are five peaks corresponding
      to different paths up and down the vibrational ladder. The positions, signs, and
      amplitudes of the peaks agree with theoretical predictions, and the intensities
      of the peaks scale linearly with concentration. Based on the concentration
      dependence and agreement between the simulations and measurements, we conclude
      that cascaded lower order signals contribute negligibly to the observed signal.

PMID- 19405596
TI  - Bottom-up derivation of an effective thermostat for united atoms simulations of
      water.
AB  - In this article we derive the effective pairwise interactions in a Langevin-type
      united atoms model of water. The interactions are determined from the
      trajectories of a detailed molecular dynamics simulation of simple point charge
      water. A standard method is used for estimating the conservative interaction,
      whereas a new "bottom-up" method is used to determine the effective dissipative
      and stochastic interactions. We demonstrate that when compared to the standard
      united atoms model, the transport properties of the coarse-grained model is
      significantly improved by the introduction of the derived dissipative and
      stochastic interactions. The results are compared to a previous study, where a
      "top-down" approach was used to obtain transport properties consistent with those
      of the simple point charge water model.

PMID- 19405598
TI  - Characterization of fluid-solid phase transition of hard-sphere fluids in
      cylindrical pore via molecular dynamics simulation.
AB  - Equation of state and structure of hard-sphere fluids confined in a cylindrical
      hard pore were investigated at the vicinity of fluid-solid transition via
      molecular dynamics simulation. By constructing artificial closed-packed
      structures in a cylindrical pore, we explicitly capture the fluid-solid phase
      transition and coexistence for the pore diameters from 2.17sigma to 15sigma.
      There exist some midpore sizes, where the phase coexistence might not exist or
      not clearly be observable. We found that the axial pressure including coexistence
      follows oscillatory behavior in different pore sizes; while the pressure tends to
      decrease toward the bulk value with increasing pore size, the dependence of the
      varying pressure on the pore size is nonmonotonic due to the substantial change
      of the alignment of the molecules. The freezing and melting densities
      corresponding to various pore sizes, which are always found to be lower than
      those of the bulk system, were accurately obtained with respect to the axial
      pressure.

PMID- 19405599
TI  - Critical cavity in the stretched fluid studied using square-gradient density
      functional model with triple-parabolic free energy.
AB  - The generic square-gradient density-functional model with triple-parabolic free
      energy is used to study the stability of a cavity introduced into the stretched
      liquid. The various properties of the critical cavity, which is the largest
      stable cavity within the liquid, are compared with those of the critical bubble
      of the homogeneous bubble nucleation. It is found that the size of the critical
      cavity is always smaller than that of the critical bubble, while the work of
      formation of the former is always higher than the latter in accordance with the
      conjectures made by Punnathanam and Corti [J. Chem. Phys. 119, 10224 (2003)]
      deduced from the Lennard-Jones fluids. Therefore their conjectures about the
      critical cavity size and the work of formation would be more general and valid
      even for other types of liquid such as metallic liquid or amorphous. However, the
      scaling relations they found for the critical cavity in the Lennard-Jones fluid
      are marginally satisfied only near the spinodal.

PMID- 19405600
TI  - Osmotic compression of droplets of hard rods: a computer simulation study.
AB  - By means of computer simulations, we study how droplets of hard, rodlike
      particles optimize their shape and internal structure under the influence of the
      osmotic compression caused by the presence of spherical particles that act as
      depletion agents. At sufficiently high osmotic pressures, the rods that make up
      the drops spontaneously align to turn them into uniaxial nematic liquid
      crystalline droplets. The nematic droplets or "tactoids" that are formed this way
      are not spherical but elongated, resulting from the competition between the
      anisotropic surface tension and the elastic deformation of the director field. In
      agreement with recent theoretical predictions, we find that sufficiently small
      tactoids have a uniform director field, while large ones are characterized by a
      bipolar director field. From the shape and director-field transformation of the
      droplets, we are able to estimate the surface anchoring strength and an average
      of the elastic constants of the hard-rod nematic.

PMID- 19405601
TI  - Structures and magnetic properties of Si(n)Mn (n = 1-15) clusters.
AB  - The structure, electronic, magnetic properties of Si(n)Mn clusters up to n=15 are
      systematically investigated using the density functional theory within the
      generalized gradient approximation. In the most stable configurations of Si(n)Mn
      clusters, the equilibrium site of Mn atom gradually moves from convex, to a
      surface, and to a concave site as the number of Si atoms varying from 1 to 15.
      Starting from n=11, the Mn atom completely falls into the center of the Si outer
      frame, forming Mn-encapsulated Si cages. Maximum peaks of second-order energy
      difference are found at n=6, 8, 10, and 12, indicating that these clusters
      possess relatively higher stability. The electronic structures and magnetic
      properties of Si(n)Mn clusters are discussed. The magnetic moment of Si(n)Mn
      clusters mainly is located on Mn atom. The 3d electrons in Mn atom play a
      dominant role in the determination of the magnetism of Mn atom in Si(n)Mn
      clusters. Furthermore, the moment of Mn atom in Si(n)Mn clusters exhibits
      oscillatory behavior and are quenched at n>7 except for n=12, mainly due to the
      charge transfer, strong hybridization between Mn 4s, 3d, 4p and Si 3s, 3p states.

PMID- 19405602
TI  - Master curves and radial distribution functions for shear dilatancy of liquid n
      hexadecane via nonequilibrium molecular dynamics simulations.
AB  - Shear dilatancy, a significant nonlinear behavior of nonequilibrium
      thermodynamics states, has been observed in nonequilibrium molecular dynamics
      (NEMD) simulations for liquid n-hexadecane fluid under extreme shear conditions.
      The existence of shear dilatancy is relevant to the relationship between the
      imposed shear rate gamma and the critical shear rate gamma(c). Consequently, as
      gamma<gamma(c), the intermolecular equilibrium distance of the fluid remains
      unchanged, while the nonequilibrium state of the fluid approaches equilibrium. In
      contrast to gamma>gamma(c), the intermolecular distance is lengthened
      substantially by strong shear deformation breaking the equilibrium thermodynamic
      state so that shear dilatancy takes place. Notably, a characteristic shear rate
      gamma(m), which depends on the root mean square molecular velocity and the
      average free molecular distance, is found in nonequilibrium thermodynamics state
      curves. Studies of the variations in the intermolecular radial distribution
      function (RDF) with respect to the shear rate provide a direct measure of the
      variation in the degree of intermolecular separation. Additionally, the
      variations of the RDF curve in the microscopic regime are consistent with those
      of the nonequilibrium thermodynamic state in the macroscopic world. By inspecting
      the overall shape of the RDF curve, it can be readily corroborated that the fluid
      of interest exists in the liquid state. More importantly, both primary
      characteristic values, the equilibrium thermodynamic state variable and a
      particular shear rate of gamma(p), are determined cautiously, with gamma(p)
      depending on the gamma(m) value and the square root of pressure. Thereby, the
      nonequilibrium thermodynamic state curves can be normalized as temperature-,
      pressure-, and density-invariant master curves, formulated by applying the Cross
      constitutive equation. Clearly, gamma(c) occurs at which a reduced shear rate
      gamma/gamma(p) approaches 0.1. Furthermore, the trends in the rates of shear
      dilatancy in both the constant-pressure and constant-volume NEMD systems under
      isothermal conditions conform to the cyclic rule of pressure, as a function of
      density and shear rate.

PMID- 19405603
TI  - On the structure of high-pressure high-temperature eta-O2.
AB  - In situ high-pressure high-temperature x-ray diffraction and optical studies have
      been conducted on solid oxygen between 10 and 20 GPa and up to 700 K. Optical
      observations and Raman spectroscopic studies have been utilized to confirm the
      existence of eta-O(2) and to identify phase behavior and phase boundaries of beta
      , epsilon- and eta-O(2) at elevated temperatures. Subsequent single-crystal
      synchrotron x-ray diffraction studies yielded the structure of the eta-O(2) phase
      at 15.9 GPa and 625 K.

PMID- 19405604
TI  - First-principles investigation of isomerization by proton transfer in beta
      fumaric acid crystal.
AB  - Crystal structure of fumaric acid was investigated by Car-Parrinello molecular
      dynamics and Path Integral molecular dynamics. We propose a mechanism of
      isomerization by proton transfer in the solid state. It is shown that the three
      conformers of fumaric acid observed in cryogenic Ar matrix are also present in
      the solid. Standard ab initio Car-Parrinello dynamics of the studied solid at 100
      K indicates that barrier height for proton transfer is too high to enable thermal
      jump over the barrier. Path Integral method in this particular case significantly
      changes proton behavior in the hydrogen bridge, and the proton tunneling process
      is observed. Vibrational spectra of investigated system HOOC-CH=CH-COOH and its
      deuterated analog DOOC-CH=CH-COOD were calculated and compared with experimental
      data.

PMID- 19405605
TI  - Electron transfer dynamics: Zusman equation versus exact theory.
AB  - The Zusman equation has been widely used to study the effect of solvent dynamics
      on electron transfer reactions. However, application of this equation is limited
      by the classical treatment of the nuclear degrees of freedom. In this paper, we
      revisit the Zusman equation in the framework of the exact hierarchical equations
      of motion formalism, and show that a high temperature approximation of the
      hierarchical theory is equivalent to the Zusman equation in describing electron
      transfer dynamics. Thus the exact hierarchical formalism naturally extends the
      Zusman equation to include quantum nuclear dynamics at low temperatures. This new
      finding has also inspired us to rescale the original hierarchical equations and
      incorporate a filtering algorithm to efficiently propagate the hierarchical
      equations. Numerical exact results are also presented for the electron transfer
      reaction dynamics and rate constant calculations.

PMID- 19405606
TI  - The structure of diaminodurene and the dynamics of the methyl groups.
AB  - Diaminodurene crystallizes in the orthorhombic space group Pbca, with eight
      molecules in the unit cell. Four inequivalent methyl groups with different
      environments exist in a molecule. The amino groups are also different, which is
      well reflected in infrared spectra. Two tunneling modes are resolved at 23.7 and
      7.0 microeV at 4.5 K. Their intensities are consistent with the presence of two
      further unresolved tunneling modes. Quasielastic spectra are composed of three
      Lorentzians of equal intensities. The two low activation energies and tunnel
      modes are modeled into consistent rotational potentials. The third activation
      energy and a librational band are used to guess the strength of the two stronger
      rotational potentials. The internal modes related to the torsional/librational
      vibrations mix with ring torsions in the range of 70-220 cm(-1). This way the
      tunnel modes couple to ring torsions whose energy determines the broadening of
      both tunnel bands. The calculations for free molecules yield mode frequencies a
      little bit lower than the experimental inelastic neutron scattering (INS) values.
      Application of theoretical methods elaborated for the crystalline state leads to
      a satisfactory consistency. It is also valid for bending modes of NH(2) groups,
      which in the solid state show much higher frequencies than in the gas phase, as
      expected.

PMID- 19405607
TI  - Theoretical investigation of methane under pressure.
AB  - We present computer simulations of liquid and solid phases of condensed methane
      at pressures below 25 GPa, between 150 and 300 K, where no appreciable molecular
      dissociation occurs. We used molecular dynamics (MD) and metadynamics techniques
      and empirical potentials in the rigid molecule approximation, whose validity was
      confirmed a posteriori by carrying out ab initio MD simulations for selected
      pressure and temperature conditions. Our results for the melting line are in
      satisfactory agreement with existing measurements. We find that the fcc crystal
      transforms into a hcp structure with four molecules per unit cell (B phase) at
      about 10 GPa and 150 K, and that the B phase transforms into a monoclinic high
      pressure phase above 20 GPa. Our results for solid/solid phase transitions are
      consistent with those of Raman studies but the phase boundaries estimated in our
      calculations are at higher pressure than those inferred from spectroscopic data.

PMID- 19405608
TI  - Nanoscale organization in piperidinium-based room temperature ionic liquids.
AB  - Here we report on the complex nature of the phase diagram of N-alkyl-N
      methylpiperidinium bis(trifluoromethanesulfonyl)imide ionic liquids using several
      complementary techniques and on their structural order in the molten state using
      small-wide angle x-ray scattering. The latter study indicates that the
      piperidinium aliphatic alkyl chains tend to aggregate, forming alkyl domains
      embedded into polar regions, similar to what we recently highlighted in the case
      of other ionic liquids.

PMID- 19405610
TI  - Effective interactions in multisite cells for adsorption in microporous
      materials.
AB  - Local, discrete models of self-interacting multisite adsorption cells have been
      shown to be able to provide a coarse-grained representation of equilibrium
      properties of small molecules adsorbed in nanoporous materials at the mesoscopic
      scale. In the present work we show how the essential statistical properties of a
      host cell of structured sites with multiple adsorption energies and particle
      particle interactions (that is the partition function, the average energy, and
      the average number of guests close to the windows connecting the cell to its
      surroundings) can be reproduced by a less-structured cell with two occupancy
      dependent adsorption energy levels.

PMID- 19405609
TI  - Nonergodic activated kinetics in polar media.
AB  - A theoretical formulation is developed for the activated kinetics when some
      subset of nuclear modes of the thermal bath is slower than the reaction and
      ergodicity of the thermal bath is not maintained. Nonergodic free energy profiles
      along the reaction coordinate are constructed by using restricted canonical
      ensembles with the phase space available to the system found by solving a self
      consistent kinetic equation. The resulting activation barrier incorporates not
      only thermodynamic parameters but also dynamical information from the time
      autocorrelation function of the solute-solvent interaction energy. The theory is
      applied to the reactions of solvolysis and charge transfer in polar media.

PMID- 19405611
TI  - First principles band structure calculations based on self-consistent screened
      Hartree-Fock exchange potential.
AB  - A screened Hartree-Fock (HF) exchange potential with the dielectric constant was
      previously reported by Shimazaki and Asai [Chem. Phys. Lett. 466, 91 (2008)], in
      which the inverse of the dielectric constant was used to represent a fraction of
      the HF exchange term. In that report, the experimentally obtained value for the
      dielectric constant was employed. Herein, we discuss a self-consistent technique,
      in which the value of the dielectric constant can be automatically determined.
      This technique enables the energy band structure to be determined without using
      the experimental value. The band energy structure of diamond is calculated, a
      self-consistent procedure is determined to give closer bandgaps compared with the
      local density approximation and the generalized gradient approximation.

PMID- 19405612
TI  - Analyte chemisorption and sensing on n- and p-channel copper phthalocyanine thin
      film transistors.
AB  - Chemical sensing properties of phthalocyanine thin-film transistors have been
      investigated using nearly identical n- and p-channel devices. P-type copper
      phthalocyanine (CuPc) has been modified with fluorine groups to convert the
      charge carriers from holes to electrons. The sensor responses to the tight
      binding analyte dimethyl methylphosphonate (DMMP) and weak binding analyte
      methanol (MeOH) were compared in air and N(2). The results suggest that the
      sensor response involves counterdoping of pre-adsorbed oxygen (O(2)). A linear
      dependence of chemical response to DMMP concentration was observed in both n- and
      p- type devices. For DMMP, there is a factor of 2.5 difference in the chemical
      sensitivity between n- and p-channel CuPc thin-film transistors, even though it
      has similar binding strength to n- and p-type CuPc molecules as indicated by the
      desorption times. The effect is attributed to the difference in the analyte
      perturbation of electron and hole trap energies in n- and p-type materials.

PMID- 19405613
TI  - Adsorption of a Ru(II) dye complex on the Au(111) surface: photoemission and
      scanning tunneling microscopy.
AB  - The adsorption of the dye molecule N3 [cis-bis(isothiocyanato)bis(2,2(')
      bipyridyl-4,4(')-dicarboxylato)-ruthenium(II)] on the Au(111) surface has been
      studied using core-level and valence photoemission and scanning tunneling
      microscopy (STM). The dye molecules were deposited in situ using ultrahigh vacuum
      electrospray deposition. The core-level spectra reveal that the molecule bonds to
      the surface via sulfur atoms with no deprotonation of the carboxylic groups. The
      STM images show that at low coverage the molecules decorate the Au(111)
      herringbone reconstruction and form uniform monolayers as the coverage is
      increased.

PMID- 19405614
TI  - Non-IPR C60 solids.
AB  - Films comprising predominantly novel isomers of C(60) [=C(60)(nIPR)] have been
      generated by low energy ion beam deposition of vibronically excited C(60)(+) onto
      graphite followed by selective sublimation of C(60)(I(h)) from the deposited
      isomer mixture. The incident ions were generated by electron impact
      ionization/fragmentation of sublimed C(70). Images of the C(60)(nIPR) films
      obtained by applying atomic force microscopy show aggregates, which we attribute
      to covalently interlinked C(60)(nIPR) units. The covalent bonds are inferred from
      the significantly higher thermal stability of the C(60)(nIPR) films compared to
      the C(60)(I(h)) van der Waals solid-as measured by thermal desorption with mass
      spectrometric detection of the C(60) mass channel (the only desorbable species).
      In contrast to the characteristic doublet structure of the occupied valence band
      in the ultraviolet photoelectron spectrum of pure C(60)(I(h)), the valence band
      of C(60)(nIPR) films exhibits a triplet feature with the additional peak
      occurring at a binding energy of approximately 2.6 eV. This is an indicator of
      the electronic modifications induced by intermolecular bonding. C(60)(nIPR) films
      exhibit a narrower band gap than found for C(60)(I(h)). They also have
      significantly different chemical reactivity toward incorporation of thermal
      energy deuterium atoms. In order to model the experimental photoelectron spectra,
      various covalently linked oligomers of (#1809)C(60)(C(2v)), the second most
      stable conventional 60-atom fullerene cage, were calculated by means of the
      density functional theory. These spectral predictions together with analogous
      previous observations on related fullerene solids such as C(58) lead us to infer
      that C(60)(nIPR) films consist of fullerene cage isomers containing one or more
      adjacent pentagon pairs, which mediate covalent cage-cage interconnection.

PMID- 19405615
TI  - Mediation of chain reactions by propagating radicals during halogenation of H
      masked Si(100): implications for atomic-scale lithography and processing.
AB  - Scanning tunneling microscopy reveals a free radical-induced surface chain
      reaction in the chlorination of nanoscale patterns on an otherwise H-passivated
      (masked) Si(100). While scanning probe methods can be used to pattern active
      surface regions with single-bond precision, follow-up selective chemical vapor
      deposition with polyatomic molecules can produce various filling characteristics.
      On active surface regions, molecular Cl(2) undergoes an atom abstraction reaction
      in which a Si dangling bond abstracts one atom of the incident Cl(2) molecule
      while the complementary Cl atom is scattered away from the initial abstraction
      site either back into the vacuum or to be captured by a second dangling bond and
      adsorbed there, or to react with a nearby adsorbed H atom to form volatile HCl.
      In contrast, I(2) undergoes only dissociative adsorption on two immediately
      neighboring dangling bonds, whereby two I-Si bonds are formed simultaneously upon
      cleavage of the I(2) bond. The different chemisorption processes of the two model
      diatomic molecular gases place intrinsic limitations on atomic-scale lithography
      and processing: Adsorption of Cl(2) results in spillage over the prepatterned
      regions of active bonds. In contrast, adsorption of I(2) is a pair process and
      results in under-filling.

PMID- 19405616
TI  - Free energy analysis for adsorption-induced lattice transition of flexible
      coordination framework.
AB  - We conduct grand canonical Monte Carlo simulations and free energy analysis for a
      gate adsorption phenomenon, which is experimentally observed in flexible
      frameworks of porous coordination polymers. Our calculations demonstrate that the
      stabilization provided by the guest adsorption drives the structural transition,
      surmounting the energy cost in creating the adsorption space due to the movement
      of the host framework. Furthermore, the existence of an energy barrier between
      two local minima in the free-energy landscape is found to result in hysteretic
      adsorption.

PMID- 19405617
TI  - Numerical approach to time-dependent quantum transport and dynamical Kondo
      transition.
AB  - An accurate and efficient numerical approach is developed for the transient
      electronic dynamics of open quantum systems at low temperatures. The calculations
      are based on a formally exact hierarchical equations of motion quantum
      dissipation theory [J. S. Jin et al., J. Chem. Phys. 128, 234703 (2008)]. We
      propose a hybrid scheme that combines the Matsubara expansion technique and a
      frequency dispersion treatment to account for reservoir correlation functions.
      The new scheme not just admits various forms of reservoir spectral functions but
      also greatly reduces the computational cost of the resulting hierarchical
      equations, especially in the low temperature regime. Dynamical Kondo effects are
      obtained and the cotunneling induced Kondo transitions are resolved in the
      transient current in response to time-dependent external voltages.

PMID- 19405618
TI  - Assembly dynamics of two-beta sheets revealed by molecular dynamics simulations.
AB  - The assembly dynamics of two beta sheets with different initial separation
      distances are explored by multiple all-atom molecular dynamics simulations with
      the presence of explicit water solvent. The beta sheet is composed of seven
      identical peptides in an antiparallel fashion. The peptide sequence is the 20-29
      segment of human Islet amyloid polypeptide. Our simulations show that the
      assembly occurs not only in the lateral direction but also along the longitudinal
      direction, which provides a new insight into the assembly pathway at the early
      stage of fibril elongation. Based on Poisson-Boltzmann free energy analysis and
      quasiharmonic configuration entropy estimation, the entropic contribution is
      found to play an important role in the longitudinal assembly. Moreover, a
      possible oligomeric state with cyclic form is suggested based on one assembly
      model found in the simulations, illustrating the polymorphic nature of
      aggregation of the amyloidogenic peptide.

PMID- 19405619
TI  - Accurately determining single molecule trajectories of molecular motion on
      surfaces.
AB  - This paper presents a method for simultaneously determining multiple trajectories
      of single molecules from sequential fluorescence images in the presence of
      photoblinking. The tracking algorithm is computationally nondemanding and does
      not assume a model for molecular motion, which allows one to determine correct
      trajectories even when a distribution of movement speeds is present. We applied
      the developed procedure to the important problem of monitoring surface motion of
      single molecules under ambient conditions. By limiting the laser exposure using
      sample scanning confocal microscopy, long-time trajectories have been extracted
      without the use of oxygen scavengers for single fluorescent molecules. Comparison
      of the experimental results to simulations showed that the smallest diffusion
      constants extracted from the trajectories are limited by detector shot noise
      giving error in locating the positions of the individual molecules. The
      simulations together with the single molecule trajectories and distributions of
      diffusion constants allowed us therefore to distinguish between mobile and
      immobile molecules. Because the analysis algorithm only requires a time series of
      images, the procedure presented here can be used in conjunction with various
      imaging methodologies to study a wide range of diffusion processes.

PMID- 19405620
TI  - Evaluating the ability to form single crystal.
AB  - Design of crystal materials requires predicting the ability of bulk materials to
      form single crystals, challenging current theories of material design. By
      introducing a concept of condensing potential (CP), it is shown via vast
      simulations of crystal growth for fcc (Ni, Cu, Al, Ar) and hcp (Mg), that
      materials with larger CP can grow into perfect single crystal more easily. Due to
      the simplicity of the calculation of CP, this method might prove a convenient way
      to evaluate the ability of materials to form single crystal.

PMID- 19405621
TI  - Hydrodynamic friction coefficients of coated spherical particles.
AB  - The complete set of hydrodynamic friction coefficients for a spherical particle
      coated with a porous layer and immersed in a viscous fluid is evaluated in
      analytic form. The coefficients allow the calculation of the flow disturbance
      caused by the coated particle for any incident flow which satisfies the creeping
      flow equations. The coefficients may be used for the evaluation of hydrodynamic
      pair interactions between coated spheres, as well as for the numerical
      calculation of many-sphere hydrodynamic interactions, and the calculation of
      transport properties of suspensions of coated spherical particles.

PMID- 19405622
TI  - Density functional study of chemical reaction equilibrium for dimerization
      reactions in slit and cylindrical nanopores.
AB  - We present a theoretical study of the effects of confinement on chemical reaction
      equilibrium in slit and cylindrical nanopores. We use a density functional theory
      (DFT) to investigate the effects of temperature, pore geometry, bulk pressure,
      transition layering, and capillary condensation on a dimerization reaction that
      mimics the nitric oxide dimerization reaction, 2NO <==> (NO)(2), in carbonlike
      slit and cylindrical nanopores in equilibrium with a vapor reservoir. In addition
      to the DFT calculations, we also utilize the reaction ensemble Monte Carlo method
      to supplement the DFT results for reaction conversion. This work is an extension
      of the previous DFT study by Tripathi and Chapman [J. Chem. Phys. 118, 7993
      (2003)] on the dimerization reactions confined in the planar slits.

PMID- 19405623
TI  - Mechanism and dynamics of the reaction of XeF2 with fluorinated Si(100): possible
      role of gas phase dissociation of a surface reaction product in plasmaless
      etching.
AB  - Xenon difluoride is observed to react with Si-Si sigma-dimer and sigma-lattice
      bonds of Si(100)2 x 1 at 150 K by single and two atom abstraction at F coverages
      above 1 ML. As in the limit of zero F coverage, a measurable fraction of the
      scattered, gas phase product of single atom abstraction, XeF, is sufficiently
      internally excited to dissociate into F and Xe atoms before detection. Using the
      XeF internal energy and orientation distributions determined in the limit of zero
      coverage, the laws of conservation of momentum, energy, and mass are applied to
      the measured F velocity and angular distributions at higher coverage to simulate
      the Xe atom velocity and angular distributions and their intensities at higher
      coverage. The simulation predicts the observed Xe atom velocity and angular
      distributions at high coverage reasonably well, largely because the exothermicity
      channeled to XeF remains approximately constant as the coverage increases. This
      constancy is an opportune consequence of the trade-off between the attractiveness
      of the potential energy surface as the coverage is increased and the dynamics of
      the XeF product along the potential surface. The energy, momentum, and mass
      conservation analysis is also used to distinguish between Xe atoms that arise
      from XeF gas phase dissociation and Xe atoms that are produced by two atom
      abstraction. This distinction enables the calculation of percentages of the
      single and two atom abstraction pathways, as well as the percentages of the two
      pathways available to the Xe atom produced by two atom abstraction, inelastic
      scattering, and desorption. Finally, the simulation reveals that between 9% and
      12% of F atoms produced by gas phase dissociation of XeF are scattered back
      toward the surface. These F atoms likely react readily with Si to form the higher
      fluorides that ultimately lead to etching. Gas phase dissociation of the
      scattered product of a surface reaction is a novel mechanism to explain the
      unique reactivity of XeF(2) to etch Si in the absence of a plasma.

PMID- 19405624
TI  - Density functional theory for adsorption of colloids on the polymer-tethered
      surfaces: effect of polymer chain architecture.
AB  - A density functional theory is used to investigate adsorption of colloids on the
      surfaces grafted by polymers of different architectures, including linear, star,
      branched, and dendritic structures. In order to calculate the direct bonding
      connectivity integral, a new numerical algorithm is proposed for polymers with
      complex architecture. A good agreement of the calculated results and the
      simulation and experimental data in studying grafted hard chain brushes confirm
      that our approach does lead a correct prediction. Accordingly, adsorption of
      colloids in the negative exponential attractive surface was studied. The effects
      of grafting density, attractive strength, molecular concentration, and size on
      adsorption were considered. The contour maps of excluded rate show that a complex
      architecture of polymer chains is much more effective in preventing adsorption
      than linear polymer brush. The results also show that the grafting density and
      complex architecture are two key factors to prevent colloidal adsorption, while
      the surface attractive strength only exhibits slight effect on colloidal
      adsorption. For polymer brushes with complex architecture, the height of
      potential of mean force is strongly dependent on the colloidal size. The larger
      the size, the higher is the potential of mean force, which means that the larger
      colloidal molecules are harder to penetrate the brush. In short, to prevent
      colloidal adsorption, it is more suitable to use the polymer brushes with complex
      architecture.

PMID- 19405625
TI  - Simulating dynamic crossover behavior of semiflexible linear polymers in solution
      and in the melt.
AB  - We present a molecular dynamics study of the dynamic scaling behavior of linear
      polymers in solution and in the melt when their character changes from fully
      flexible to semiflexible. The stiffness of the chains is determined by a bending
      potential. It is shown that the relaxation times tau(p) characterizing the
      internal dynamics of the polymer chains as well as the mean square mode
      amplitudes <chi(p)(2)> exhibit a clear crossover from Rouse to bending modes with
      increasing mode number p. For small mode numbers p the well-known p(-2) Rouse
      behavior is observed, whereas large mode numbers exhibit the p(-4) scaling,
      typical of the bending modes of semiflexible chains. We study the extension and
      the onset of the region where the crossover from p(-2) to p(-4) behavior occurs.
      With increasing stiffness of the chains we observe a shift of the crossover
      domain to smaller p-values. We also investigate the effect of chain stiffness on
      the monomer dynamics, based on their mean square displacements. Finally, we
      compare our results to previous simulations, where the scaling behavior of
      semiflexible chains was studied and which were restricted to a smaller range of
      persistence lengths l(p) and p values.

PMID- 19405626
TI  - Conformational behavior of diblock comb copolymers.
AB  - The conformational behavior of a single diblock copolymer chain with comb blocks
      is studied by computer simulation. The comb blocks have equal lengths of the
      backbones and side chains and differ only by the degree of grafting of the side
      chains. The collapse behavior is studied for two cases: (i) comb diblock
      copolymer with attracting backbones of the blocks and swollen side chains and
      (ii) comb diblock copolymer with attracting monomer units of the side chains of
      the blocks and swollen backbones. In both cases the conformation of a globule
      with a tail is observed when one of the block collapses while the other stays
      swollen. At high attraction micellar-type globules are formed. The core of the
      micelle consists of attracting monomeric units and the soluble segments (side
      chains or backbones) comprise the corona. It is shown that separation of
      monomeric units belonging to different blocks can take place both in the core and
      in the corona regions of the micelle.

PMID- 19405627
TI  - Periodic density functional theory studies of Li-doped polythiophene: dependence
      of electronic and structural properties on dopant concentration.
AB  - We report periodic B3LYP6-31G(**) density functional theory calculations on Li
      doped polythiophene at various dopant concentrations using (SC(4)H(2))(m)Li(2)
      unit cells for m=2, 6, and 10. Uniform doping by Li atoms and by pairs of Li
      atoms on adjacent thiophene rings are considered with the primary aim of
      comparing polaron versus bipolaron properties. Properties examined include
      geometries, charge distributions, polaron/bipolaron formation energies, dopant
      binding energies, band structures, and densities of states.

PMID- 19405628
TI  - Equilibrium polymerization models of re-entrant self-assembly.
AB  - As is well known, liquid-liquid phase separation can occur either upon heating or
      cooling, corresponding to lower and upper critical solution phase boundaries,
      respectively. Likewise, self-assembly transitions from a monomeric state to an
      organized polymeric state can proceed either upon increasing or decreasing
      temperature, and the concentration dependent ordering temperature is
      correspondingly called the "floor" or "ceiling" temperature. Motivated by the
      fact that some phase separating systems exhibit closed loop phase boundaries with
      two critical points, the present paper analyzes self-assembly analogs of re
      entrant phase separation, i.e., re-entrant self-assembly. In particular, re
      entrant self-assembly transitions are demonstrated to arise in thermally
      activated equilibrium self-assembling systems, when thermal activation is more
      favorable than chain propagation, and in equilibrium self-assembly near an
      adsorbing boundary where strong competition exists between adsorption and self
      assembly. Apparently, the competition between interactions or equilibria
      generally underlies re-entrant behavior in both liquid-liquid phase separation
      and self-assembly transitions.

PMID- 19405630
TI  - Symmetry and order in systems chemistry.
AB  - Systems chemistry seeks to find fundamental insights into the emergent properties
      of complex systems and living matter. Thus chemists use a "bottom-up" approach
      for the design and integration of simple elements as a means of producing self
      organized systems that can serve as feasible models. Toward this end, networks of
      replicating molecules have been produced and their dynamic behavior was analyzed
      both experimentally and by simulation. In this paper we describe our analysis of
      the reaction mechanisms which build up these systems. To do so, we revisit models
      for self-replication and template assisted catalysis and expand them to describe
      the kinetics of small catalytic networks. From symmetry requirements and
      reasonable chemical assumptions, it is shown that the construction of
      increasingly complex networks requires higher order catalysis. Specifically, we
      explain why low order catalysis, in which a monomeric molecule serves as a
      template, is incapable of efficiently activating cooperative cross catalytic
      elements and basic asymmetric sequentially linked units, so that at least second
      order catalysis, in which dimeric molecules serve as templates, is necessary.
      These cooperative and asymmetric linked units are required components of more
      complex molecular networks. We compare our results with other experimental
      evidence for the centrality of higher order catalysis and discuss the
      implications of our results on molecular self-organization and other aspects of
      systems chemistry.

PMID- 19405631
TI  - The structure of random packings of freely jointed chains of tangent hard
      spheres.
AB  - We analyze the structure of dense random packings of freely jointed chains of
      tangent hard spheres as a function of concentration (packing density) with
      particular emphasis placed on the behavior in the vicinity of their maximally
      random jammed (MRJ) state. Representative configurations over the whole density
      range are generated through extensive off-lattice Monte Carlo simulations on
      systems of average chain lengths ranging from N=12 to 1000 hard spheres. Several
      measures of order are used to quantitatively describe either local structure
      (sphere arrangements and bonded geometry) or global behavior (chain conformations
      and statistics). In addition, the employed measures are used to elucidate the
      effect of connectivity on structure, by comparing monatomic and chain assemblies
      of hard spheres at the MRJ state.

PMID- 19405629
TI  - Absolute FKBP binding affinities obtained via nonequilibrium unbinding
      simulations.
AB  - We compute the absolute binding affinities for two ligands bound to the FKBP
      protein using nonequilibrium unbinding simulations. The methodology is
      straightforward requiring little or no modification to many modern molecular
      simulation packages. The approach makes use of a physical pathway, eliminating
      the need for complicated alchemical decoupling schemes. We compare our
      nonequilibrium results to those obtained via a fully equilibrium approach and to
      experiment. The results of this study suggest that to obtain accurate results
      using nonequilibrium approaches one should use the stiff-spring approximation
      with the second cumulant expansion. From this study we conclude that
      nonequilibrium simulation could provide a simple means to estimate protein-ligand
      binding affinities.

PMID- 19405632
TI  - Synchrotron investigation on the sheared structure evolution of syndiotactic
      polypropylene crystallization process.
AB  - The final structure of molten syndiotactic polypropylene (sPP) sheared under
      different conditions was investigated by synchrotron small-angle x-ray scattering
      (SAXS) and wide-angle x-ray diffraction (WAXD) techniques to elucidate the shear
      effects on sPP crystalline structure. The results obtained from the WAXD show
      that there is no variation on crystalline form but a little difference on the
      orientation of the 200 reflection. The SAXS data indicate that the lamellar
      thickness and long period have not been affected by shear but the lamellar
      orientation is dependent on shear. The experimental data of sPP crystallization
      from sheared melt may indicate a mesophase structure that is crucial to the shear
      effects on the final polymer multiscale crystalline structures.

PMID- 19405633
TI  - Theoretical evidence of barrier-free proton transfer in 7-azaindole-water cluster
      anions.
AB  - Water clusters of 7-azaindole (7AI) and its radical anion with up to three water
      molecules have been investigated by B3LYP and MP2 methods. While the adiabatic
      electron affinities (AEAs) of 7AI(H(2)O)(n=0,1) and the most stable configuration
      of 7AI(H(2)O)(2) were calculated to be negative, the AEAs of 7AI(H(2)O)(3) were
      found to be positive, consistent with the experimental observation that the
      cluster anions of 7AI(-)(H(2)O)(n) start to appear continuously in mass spectra
      when n > or = 3. However, some high-energy configurations of 7AI(H(2)O)(2) were
      found to have potential for capturing excess electrons and forming stable anions.
      The B3LYP approach was shown to systematically overestimate the AEA due to its
      insufficient description of buckling of conjugated ring induced by electron
      attachment. The computational results show that the activation energy of proton
      transfer in 7AI(-)(H(2)O)(n) decreases as the number of water molecule increases.
      For n = 3, electron attachment was found to induce a barrier-free proton transfer
      from water to 7AI(-), resulting in the formation of a neutral radical of
      protonated 7AI solvated by a water cluster of hydroxyl anion, OH(-)(H(2)O)(2).
      The protonated structures were found to be lower in energy than the fully
      tautomerized structures where the tautomeric 7AI radical anion is solvated by a
      neutral water cluster. In addition, the tautomeric structures were found to be
      kinetically unstable with respect to the reverse transformation to the protonated
      structures. These results indicate that the protonated configuration of 7AI(
      )(H(2)O)(3) is the major species detected in molecular beam experiments. This
      conclusion was further confirmed by the calculations of vertical detachment
      energies of cluster anions. The van der Waals structures of 7AI(-)(H(2)O)(3), in
      which the water molecules locate over the 7AI conjugated ring and point their O-H
      bonds toward the pi-electron cloud, were explored as well. Comparison of the
      protonation energies for DNA base anions and 7AI anion suggests that analogous
      proton-transfer reactions might occur in the water clusters of DNA base anions
      with only few water molecules.

PMID- 19405634
TI  - Formation of lamellar structures from spherical particles.
AB  - We report disorder to lamellar transition in a system of spherically symmetric
      particles where the interparticle potential consists of a short-ranged attraction
      and a longer-ranged repulsion. The system provides a simplified model for aqueous
      dispersions of colloidal particles and globular proteins that may exhibit
      stable/metastable clusters or microscopic phases. By using a non-mean-field
      density functional theory, we predict that under appropriate conditions, a
      lamellar phase with alternating condensed and dilute layers of particles is
      thermodynamically more stable than a uniform disordered phase at the same
      temperature and molecular number density. Formation of the lamellar structure may
      prohibit the macroscopic fluid-fluid phase transition. At a given condition, the
      width of the condensed lamellar layers increases with the overall particle
      density but the trend is opposite for the dilute lamellar layers. A minimal
      lamellar periodicity is obtained when the condensed and dilute layers have
      approximately the same thickness.

PMID- 19405635
TI  - Nuclear relaxation and critical fluctuations in membranes containing cholesterol.
AB  - Nuclear resonance frequencies in bilayer membranes depend on lipid composition.
      Our calculations describe the combined effects of composition fluctuations and
      diffusion on nuclear relaxation near a miscibility critical point. Both tracer
      and gradient diffusion are included. The calculations involve correlation
      functions and a correlation length xi=xi(0)T/(T-T(c)), where T-T(c) is
      temperature above the critical temperature and xi(0) is a parameter of molecular
      length. Several correlation functions are examined, each of which is related in
      some degree to the Ising model correlation function. These correlation functions
      are used in the calculation of transverse deuterium relaxation rates in magic
      angle spinning and quadrupole echo experiments. The calculations are compared
      with experiments that report maxima in deuterium and proton nuclear relaxation
      rates at the critical temperature [Veatch et al., Proc. Nat. Acad. Sci. U.S.A.
      104, 17650 (2007)]. One Ising-model-related correlation function yields a maximum
      1/T(2) relaxation rate at the critical temperature for both magic angle spinning
      and quadrupole echo experiments. The calculated rates at the critical temperature
      are close to the experimental rates. The rate maxima involve relatively rapid
      tracer diffusion in a static composition gradient over distances of up to 10-100
      nm.

PMID- 19405636
TI  - Effect of knotting on polymer shapes and their enveloping ellipsoids.
AB  - We simulate freely jointed chains to investigate how knotting affects the overall
      shapes of freely fluctuating circular polymeric chains. To characterize the
      shapes of knotted polygons, we construct enveloping ellipsoids that minimize
      volume while containing the entire polygon. The lengths of the three principal
      axes of the enveloping ellipsoids are used to define universal size and shape
      descriptors analogous to the squared radius of gyration and the inertial
      asphericity and prolateness. We observe that polymeric chains forming more
      complex knots are more spherical and also more prolate than chains forming less
      complex knots with the same number of edges. We compare the shape measures,
      determined by the enveloping ellipsoids, with those based on constructing
      inertial ellipsoids and explain the differences between these two measures of
      polymer shape.

PMID- 19405637
TI  - Profiles of equilibrium constants for self-association of aromatic molecules.
AB  - Analysis of the noncovalent, noncooperative self-association of identical
      aromatic molecules assumes that the equilibrium self-association constants are
      either independent of the number of molecules (the EK-model) or change
      progressively with increasing aggregation (the AK-model). The dependence of the
      self-association constant on the number of molecules in the aggregate (i.e., the
      profile of the equilibrium constant) was empirically derived in the AK-model but,
      in order to provide some physical understanding of the profile, it is proposed
      that the sources for attenuation of the equilibrium constant are the loss of
      translational and rotational degrees of freedom, the ordering of molecules in the
      aggregates and the electrostatic contribution (for charged units). Expressions
      are derived for the profiles of the equilibrium constants for both neutral and
      charged molecules. Although the EK-model has been widely used in the analysis of
      experimental data, it is shown in this work that the derived equilibrium
      constant, K(EK), depends on the concentration range used and hence, on the
      experimental method employed. The relationship has also been demonstrated between
      the equilibrium constant K(EK) and the real dimerization constant, K(D), which
      shows that the value of K(EK) is always lower than K(D).

PMID- 19405638
TI  - Coherence resonance induced by the deviation of non-Gaussian noise in coupled
      Hodgkin-Huxley neurons.
AB  - Neurons are noisy elements. Noise arises from both intrinsic and extrinsic
      sources. In this paper, we numerically study the effect of a particular kind of
      colored non-Gaussian noise (NGN), mainly of its deviation q from Gaussian noise,
      on the collective firing in bidirectionally coupled deterministic Hodgkin-Huxley
      neurons. It is found that the coefficient of variation (CV), characterizing the
      temporal regularity of the collective spikes, nonlinearly changes with increasing
      q and passes through a minimum at an intermediate optimal q where the collective
      spiking becomes most regular, which represents the presence of coherence
      resonance (CR). We also present a global view of CV as a function of q and neuron
      number N under various appropriate values of noise intensity. For each value of
      noise intensity, there is an island present in the contour plot, which
      sufficiently demonstrates the phenomenon of "q-induced CR." This phenomenon,
      termed as q-induced CR, shows that there is an optimal deviation of the NGN by
      which the coupled neurons may behave most periodically in time. Our results
      provide a novel constructive role of the deviation of the NGN in information
      processing and signal transduction in real neural systems.

PMID- 19405639
TI  - On nonadiabatic calculation of dipole moments.
AB  - We show that a recent non-Born-Oppenheimer calculation of dipole moments exhibits
      obscure points and is not consistent with the well known Hellmann-Feynman
      theorem.

PMID- 19405640
TI  - Comment on "Dipole moment and hyperfine parameters of H(35)Cl and D(35)Cl" [J.
      Chem. Phys. 53, 1686 (1970)].

PMID- 19405644
TI  - Invited article: data analysis of the floating potential measurement unit aboard
      the international space station.
AB  - We present data from the Floating Potential Measurement Unit (FPMU) that is
      deployed on the starboard truss of the International Space Station. The FPMU is a
      suite of instruments capable of redundant measurements of various plasma
      parameters. The instrument suite consists of a floating potential probe, a wide
      sweeping spherical Langmuir probe, a narrow-sweeping cylindrical Langmuir probe,
      and a plasma impedance probe. This paper gives a brief overview of the
      instrumentation and the received data quality, and then presents the algorithm
      used to reduce I-V curves to plasma parameters. Several hours of data are
      presented from August 5, 2006 and March 3, 2007. The FPMU derived plasma density
      and temperatures are compared with the International Reference Ionosphere (IRI)
      and Utah State University-Global Assimilation of Ionospheric Measurement (USU
      GAIM) models. Our results show that the derived in situ density matches the USU
      GAIM model better than the IRI, and the derived in situ temperatures are
      comparable to the average temperatures given by the IRI.

PMID- 19405645
TI  - A Fourier transform spectrometer without a beam splitter for the vacuum
      ultraviolet range: From the optical design to the first UV spectrum.
AB  - We describe a Fourier transform (FT) spectrometer designed to operate down to 60
      nm (20 eV) on a synchrotron radiation beamline for high resolution absorption
      spectrometry. As far as we know, such an instrument is not available below 140 nm
      mainly because manufacturing accurate and efficient beam splitters remains a
      major problem at these wavelengths, especially if a wide bandwidth operation is
      desired. In order to overcome this difficulty, we developed an interferometer
      based on wave front division instead of amplitude division. It relies on a
      modified Fresnel bimirror configuration that requires only flat mirrors. The
      instrument provides path difference scanning through the translation of one
      reflector. During the scanning, the moving reflector is controlled by an optical
      system that keeps its direction constant within a tolerable value and provides an
      accurate interferometric measurement of the path difference variation. Therefore,
      a regular interferogram sampling is obtained, producing a nominal spectral
      impulse response and an accurate spectral calibration. The first results
      presented in this paper show a measured spectral resolution of delta(sigma)=0.33
      cm-1 (interval between spectral samples). This was obtained with a sampling
      interval of 29 nm (path difference) and 512 K samples from a one-sided
      interferogram using a cosine FT. Such a sampling interval should allow the
      recording of large bandwidth spectra down to lambda=58 nm with an ultimate
      resolving power of 500,000 at this wavelength. In order to check the instrument
      performances, we first recorded an interferogram from a He-Ne stabilized laser.
      This provided the actual spectral impulse function, which was found to be fully
      satisfactory. The determination of the impulse response distortion and of the
      noise on the vacuum ultraviolet (VUV) spectral range provided accurate
      information in the sampling error profile over a typical scan. Finally, the
      instrument has been moved to the SU5 undulator-based synchrotron radiation
      beamline (Super-ACO facility, LURE, Orsay, France). A high resolution spectrum of
      O2 (the Schumann-Runge absorption bands, 185-200 nm) was computed from recorded
      interferograms using the beamline monochromator at the zeroth order to feed the
      instrument with an 11% relative bandwidth "white" beam (2003). These UV
      measurements are very close to those found in the literature, showing nominal
      performances of the FT spectrometer that should translate into an unprecedented
      resolving power at shortest VUV wavelengths. A recent upgrade (2007) and future
      developments will be discussed in light of the current installation of the
      upgraded FT spectrometer as a permanent endstation for ultrahigh resolution
      absorption spectrometry on the VUV beamline DESIRS at SOLEIL, the new French
      third generation synchrotron facility.

PMID- 19405646
TI  - Use of ruthenium dyes for subnanosecond detector fidelity testing in real time
      transient absorption.
AB  - Transient absorption spectroscopy is a powerful tool for the study of
      photoreactions on time scales from femtoseconds to seconds. Typically, reactions
      slower than approximately 1 ns are recorded by the "classical" technique; the
      reaction is triggered by an excitation flash, and absorption changes accompanying
      the reaction are recorded in real time using a continuous monitoring light beam
      and a detection system with sufficiently fast response. The pico- and femtosecond
      region can be accessed by the more recent "pump-probe" technique, which
      circumvents the difficulties of real time detection on a subnanosecond time
      scale. This is paid for by accumulation of an excessively large number of shots
      to sample the reaction kinetics. Hence, it is of interest to extend the classical
      real time technique as far as possible to the subnanosecond range. In order to
      identify and minimize detection artifacts common on a subnanosecond scale, like
      overshoot, ringing, and signal reflections, rigorous testing is required of how
      the detection system responds to fast changes of the monitoring light intensity.
      Here, we introduce a novel method to create standard signals for detector
      fidelity testing on a time scale from a few picoseconds to tens of nanoseconds.
      The signals result from polarized measurements of absorption changes upon
      excitation of ruthenium complexes {[Ru(bpy)(3)](2+) and a less symmetric
      derivative} by a short laser flash. Two types of signals can be created depending
      on the polarization of the monitoring light with respect to that of the
      excitation flash: a fast steplike bleaching at magic angle and a
      monoexponentially decaying bleaching for parallel polarizations. The lifetime of
      the decay can be easily varied via temperature and viscosity of the solvent. The
      method is applied to test the performance of a newly developed real time
      transient absorption setup with 300 ps time resolution and high sensitivity.

PMID- 19405647
TI  - A multimodal spectroscopy system for real-time disease diagnosis.
AB  - The combination of reflectance, fluorescence, and Raman spectroscopy-termed
      multimodal spectroscopy (MMS)-provides complementary and depth-sensitive
      information about tissue composition. As such, MMS is a promising tool for
      disease diagnosis, particularly in atherosclerosis and breast cancer. We have
      developed an integrated MMS instrument and optical fiber spectral probe for
      simultaneous collection of all three modalities in a clinical setting. The MMS
      instrument multiplexes three excitation sources, a xenon flash lamp (370-740 nm),
      a nitrogen laser (337 nm), and a diode laser (830 nm), through the MMS probe to
      excite tissue and collect the spectra. The spectra are recorded on two
      spectrograph/charge-coupled device modules, one optimized for visible wavelengths
      (reflectance and fluorescence) and the other for the near-infrared (Raman), and
      processed to provide diagnostic parameters. We also describe the design and
      calibration of a unitary MMS optical fiber probe 2 mm in outer diameter,
      containing a single appropriately filtered excitation fiber and a ring of 15
      collection fibers, with separate groups of appropriately filtered fibers for
      efficiently collecting reflectance, fluorescence, and Raman spectra from the same
      tissue location. A probe with this excitation/collection geometry has not been
      used previously to collect reflectance and fluorescence spectra, and thus
      physical tissue models ("phantoms") are used to characterize the probe's
      spectroscopic response. This calibration provides probe-specific modeling
      parameters that enable accurate extraction of spectral parameters. This clinical
      MMS system has been used recently to analyze artery and breast tissue in vivo and
      ex vivo.

PMID- 19405649
TI  - Advanced photoelectric effect experiment beamline at Elettra: A surface science
      laboratory coupled with Synchrotron Radiation.
AB  - We report the main characteristics of the advanced photoelectric effect
      experiments beamline, operational at Elettra storage ring, featuring a fully
      independent double branch scheme obtained by the use of chicane undulators and
      able to keep polarization control in both linear and circular mode. The paper
      describes the novel technical solutions adopted, namely, (a) the design of a
      quasiperiodic undulator resulting in optimized suppression of higher harmonics
      over a large photon energy range (10-100 eV), (b) the thermal stability of optics
      under high heat load via cryocoolers, and (c) the end station interconnected
      setup allowing full access to off-beam and on-beam facilities and, at the same
      time, the integration of users' specialized sample growth chambers or modules.

PMID- 19405648
TI  - Three-dimensional fluence rate measurement and data acquisition system for
      minimally invasive light therapies.
AB  - Light based therapies such as photodynamic therapy are in need of advanced tools
      for light fluence rate dosimetry and monitoring within the context of therapy
      planning and light delivery to ensure maximum treatment efficacy. The use of a
      single, multisensor fiber-based fluorescent probe capable of performing spatially
      resolved fluence rate measurements along an axis was demonstrated. This work
      extends the previous technique and describes a fluence rate quantification system
      able to employ up to 12 multisensor probes to simultaneously measure fluence rate
      distribution throughout a 3D treatment volume. The system optoelectronics
      provides for sensor calibration, data acquisition, and weighted least-squares
      processing to extract localized fluence rate information in real-time. Core
      components include an integrating cylinder for source sensor calibration, a 2D
      back thin CCD detector for sensor signal detection from multiple probes, high
      speed data acquisition card, and custom software for real-time extraction of
      fluence rate information from all sensors.

PMID- 19405650
TI  - Fluorescence decay-time constants in organic liquid scintillators.
AB  - The fluorescence decay-time constants have been measured for several scintillator
      mixtures based on phenyl-o-xylylethane (PXE) and linear alkylbenzene (LAB)
      solvents. The resulting values are of relevance for the physics performance of
      the proposed large-volume liquid scintillator detector Low Energy Neutrino
      Astronomy (LENA). In particular, the impact of the measured values to the search
      for proton decay via p-->K(+)nu is evaluated in this work.

PMID- 19405651
TI  - Rapidly pulsed helium droplet source.
AB  - A pulsed valve connected to a closed-cycle cryostat was optimized for producing
      helium droplets. The pulsed droplet beam appeared with a bimodal size
      distribution. The leading part of the pulse consists of droplets suitable for
      doping with molecules. The average size of this part can be varied between 10(4)
      and 10(6) helium atoms, and the width of the distribution is smaller as compared
      to a continuous-flow droplet source. The system has been tested in a single pulse
      mode and at repetition rates of up to 500 Hz with almost constant intensity. The
      droplet density was found to be increased by more than an order of magnitude as
      compared to a continuous-flow droplet source.

PMID- 19405652
TI  - Development of a compact electron ion coincidence analyzer using a coaxially
      symmetric mirror electron energy analyzer and a miniature polar-angle-resolved
      time-of-flight ion mass spectrometer with four concentric anodes.
AB  - A compact electron ion coincidence (EICO) analyzer that uses a coaxially
      symmetric mirror electron energy analyzer and a miniature polar-angle-resolved
      time-of-flight ion mass spectrometer with four concentric anodes was developed
      for surface science and surface analysis. The apparatus is especially useful in
      the study of ion desorption stimulated by an Auger process because information on
      the mass, yield, desorption polar angle, and kinetic energy of ions can be
      obtained for the selected core-ionization-final-states or the selected Auger
      final-states. The analyzer can be used also for analysis of the configuration of
      specific surface molecules because the desorption polar angles reflect the
      direction of surface bonds. The EICO analyzer was evaluated by measuring polar
      angle-resolved-ion yield spectra and coincidence spectra of Auger-electron and
      polar-angle-resolved H(+) from condensed water.

PMID- 19405653
TI  - Arc discharge ion source for europium and other refractory metals implantation.
AB  - The best method for the impurity doping to the host material is the ion
      implantation. Due to high melting point of the rare earth standard metal ion
      sources are useless. One of the solution is to use chemical compounds of rare
      earths characterized by low melting point. In this paper we describe the novel
      design of the ion source suitable for refractory metal (e.g., rare earths) ion
      implantation. The dependencies of Eu(+) current on cathode and arc currents as
      well as on hydrogen flow are presented. Europium (III) chloride as the source of
      the europium atoms was used. Europium ions were produced during collisions of
      evaporated and decomposed EuCl(3) molecules with fast electrons. The typical
      current of the europium ion beam extracted from the ion source was 25 microA for
      the extraction voltage of 25 kV. The ion source works without maintenance breaks
      for approximately 50 h, which enables high dose implantation. The presented ion
      source needs neither advanced high power supplies nor high vacuum regime.

PMID- 19405655
TI  - Multichannel microwave interferometer for the levitated dipole experiment.
AB  - A four-channel microwave interferometer (center frequency: 60 GHz) has been
      constructed to measure plasma density profiles in the levitated dipole experiment
      (LDX). The LDX interferometer has a unique design owing to the unique geometry of
      LDX. The main design features of the interferometer are: (1) the transmitted beam
      traverses the plasma entirely in O-mode; (2) the interferometer is a heterodyne
      system employing two free-running oscillators; (3) four signals of data are
      received from just on transmitted beam; (4) phase shifts are detected in
      quadrature. Calibration tests demonstrate that the interferometer measures phase
      shifts with an uncertainty of approximately 5 degrees . Plasma densities in LDX
      corresponding to phase shifts of up to 5pi are routinely and successfully
      measured.

PMID- 19405654
TI  - Porous plug gas injection systems for studies of hydrocarbon dissociation and
      transport in the DIII-D tokamak.
AB  - A probe has been designed, constructed, and successfully used to inject methane
      into the DIII-D lower divertor in a manner imitating natural release by chemical
      erosion. This porous plug injector (PPI) probe consists of a self-contained gas
      reservoir with an integrated pressure gauge and a 3 cm diameter porous surface
      through which gas is injected into the lower divertor of the tokamak. The probe
      is positioned flush with the divertor target surface by means of the divertor
      materials evaluation system. Two gas delivery systems were developed: in the
      first, gas flow is regulated by a remotely controlled microvalve and in the
      second by a fixed micro-orifice flow restrictor. Because of the large area of the
      porous surface through which gas is admitted, the injected hydrocarbon molecules
      see a local carbon surface (>90% carbon) similar to that seen by hydrocarbons
      being emitted by chemical sputtering from surrounding carbon tiles. The
      distributed gas source also reduces the disturbance to the local plasma while
      providing sufficient signal for spectroscopic detection. In situ spectroscopic
      measurements with the PPI in DIII-D allow the direct calibration of response for
      measured plasma conditions from a known influx of gas.

PMID- 19405656
TI  - A digital control system for external magnetohydrodynamic modes in tokamak
      plasmas.
AB  - A feedback system for controlling external, long-wavelength magnetohydrodynamic
      activity is described. The system is comprised of a network of localized magnetic
      pickup and control coils driven by four independent, low-latency field
      programable gate array controllers. The control algorithm incorporates digital
      spatial filtering to resolve low mode number activity, temporal filtering to
      correct for frequency-dependent amplitude and phase transfer effects in the
      control hardware, and a Kalman filter to distinguish the unstable plasma mode
      from noise.

PMID- 19405657
TI  - Seeding magnetic fields for laser-driven flux compression in high-energy-density
      plasmas.
AB  - A compact, self-contained magnetic-seed-field generator (5 to 16 T) is the
      enabling technology for a novel laser-driven flux-compression scheme in laser
      driven targets. A magnetized target is directly irradiated by a kilojoule or
      megajoule laser to compress the preseeded magnetic field to thousands of teslas.
      A fast (300 ns), 80 kA current pulse delivered by a portable pulsed-power system
      is discharged into a low-mass coil that surrounds the laser target. A >15 T
      target field has been demonstrated using a <100 J capacitor bank, a laser
      triggered switch, and a low-impedance (<1 Omega) strip line. The device has been
      integrated into a series of magnetic-flux-compression experiments on the 60 beam,
      30 kJ OMEGA laser [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)]. The
      initial application is a novel magneto-inertial fusion approach [O. V. Gotchev et
      al., J. Fusion Energy 27, 25 (2008)] to inertial confinement fusion (ICF), where
      the amplified magnetic field can inhibit thermal conduction losses from the hot
      spot of a compressed target. This can lead to the ignition of massive shells
      imploded with low velocity-a way of reaching higher gains than is possible with
      conventional ICF.

PMID- 19405658
TI  - Diagnostic development in precise opacity measurement of radiatively heated Al
      plasma on Shenguang II laser facility.
AB  - Simultaneous measurements of the self-emission spectrum, the backlighting source
      spectrum, and the transmission spectrum in one shot, which reduce the
      experimental uncertainties from shot-to-shot fluctuation, are essential for
      precise opacity experiments. In order to achieve precise absorption spectrum of
      Al plasmas, a special half sample sandwich target was designed and short
      backlighter was used to provide time- and space-resolving diagnostics on the
      Shenguang II high power laser facility. In the measurement, a cylindrical cavity
      with CH foam baffles was used to provide a clean x-ray radiation environment for
      sample heating. The x-ray source spectrum, the transmission spectrum, and the
      self-emission spectrum of the soft x-ray heated Al sample were recorded in one
      shot with a penta-erythritol tetrakis (hydroxymethy) methane C(CH(2)OH)(4) (PET)
      crystal spectrometer by using the point-projection method. Experimental results
      have been compared with the calculation results of a detailed level accounting
      opacity code.

PMID- 19405659
TI  - Measurements of plasma potential in high-pressure microwave plasmas.
AB  - Plasma potential of a high-pressure ( approximately 1 Torr) microwave-generated
      argon plasma is measured using a Langmuir probe and a cold emissive probe. The
      operation of a hot emissive probe in a high-pressure plasma has been very
      difficult due to frequent burn-outs and significantly reduced lifetime of the
      probe filament, which, in turn, limits the possibility of collecting a wide range
      of data. The I-V characteristics from both Langmuir and emissive probes are
      interpreted using the collisionless probe theory since the collision correction
      factor is not very significant. The plasma potential determined from both
      Langmuir and cold emissive probe characteristics agrees well with one another and
      is observed to be dependent on the operating gas pressure but relatively
      unchanged as a function of the microwave power. An average plasma potential
      determined over the operating range of microwave powers varies nonlinearly with
      the gas pressure.

PMID- 19405660
TI  - A microcomputed tomography guided fluorescence tomography system for small animal
      molecular imaging.
AB  - A prototype small animal imaging system was created for coupling fluorescence
      tomography (FT) with x-ray microcomputed tomography (microCT). The FT system has
      the potential to provide synergistic information content resultant from using
      microCT images as prior spatial information and then allows overlay of the FT
      image onto the original microCT image. The FT system was designed to use single
      photon counting to provide maximal sensitivity measurements in a noncontact
      geometry. Five parallel detector locations are used, each allowing simultaneous
      sampling of the fluorescence and transmitted excitation signals through the
      tissue. The calibration and linearity range performance of the system are
      outlined in a series of basic performance tests and phantom studies. The ability
      to image protoporphyrin IX in mouse phantoms was assessed and the system is ready
      for in vivo use to study biological production of this endogenous marker of
      tumors. This multimodality imaging system will have a wide range of applications
      in preclinical cancer research ranging from studies of the tumor microenvironment
      and treatment efficacy for emerging cancer therapeutics.

PMID- 19405661
TI  - A metrological large range atomic force microscope with improved performance.
AB  - A metrological large range atomic force microscope (Met. LR-AFM) has been set up
      and improved over the past years at Physikalisch-Technische Bundesanstalt (PTB).
      Being designed as a scanning sample type instrument, the sample is moved in three
      dimensions by a mechanical ball bearing stage in combination with a compact z
      piezostage. Its topography is detected by a position-stationary AFM head. The
      sample displacement is measured by three embedded miniature homodyne
      interferometers in the x, y, and z directions. The AFM head is aligned in such a
      way that its cantilever tip is positioned on the sample surface at the
      intersection point of the three interferometer measurement beams for satisfying
      the Abbe measurement principle. In this paper, further improvements of the Met.
      LR-AFM are reported. A new AFM head using the beam deflection principle has been
      developed to reduce the influence of parasitic optical interference phenomena.
      Furthermore, an off-line Heydemann correction method has been applied to reduce
      the inherent interferometer nonlinearities to less than 0.3 nm (p-v). Versatile
      scanning functions, for example, radial scanning or local AFM measurement
      functions, have been implemented to optimize the measurement process. The
      measurement software is also improved and allows comfortable operations of the
      instrument via graphical user interface or script-based command sets. The
      improved Met. LR-AFM is capable of measuring, for instance, the step height,
      lateral pitch, line width, nanoroughness, and other geometrical parameters of
      nanostructures. Calibration results of a one-dimensional grating and a set of
      film thickness standards are demonstrated, showing the excellent metrological
      performance of the instrument.

PMID- 19405662
TI  - Reconstruction of atomic force microscopy image by using nanofabricated tip
      characterizer toward the actual sample surface topography.
AB  - The atomic force microscopy (AFM) image is a dilation of the sample surface
      topography due to the finite-sized AFM tip. We accurately estimated the tip apex
      shape with a nanofabricated Si tip characterizer and applied the estimated tip
      shape function to a dilation-erosion algorithm for image reconstruction. The
      reconstructed images from the original AFM images attained with different AFM
      tips show consistent surface features and closely match the high-resolution field
      emission scanning electron microscope image. The results demonstrate the
      reliability of our method and suggest the importance of AFM image reconstruction
      for a variety of technologies requiring new strategies of measuring,
      interpreting, manipulating, and positioning in the submicrometer and nanometer
      range.

PMID- 19405663
TI  - Development of wearable optical topography system for mapping the prefrontal
      cortex activation.
AB  - Optical topography (OT) based on near infrared spectroscopy is effective for
      measuring changes in the concentrations of oxygenated hemoglobin (oxy-Hb) and
      deoxygenated hemoglobin (deoxy-Hb) in the brain. It can be used to investigate
      brain functions of subjects of all ages because it is noninvasive and less
      constraining for subjects. Conventional OT systems use optical fibers to
      irradiate the scalp and detect light transmitted through the tissue in the human
      head, but optical fibers limit the subject's head position, so some small systems
      have been developed without using optical fibers. These systems, however, have a
      small number of measurement channels. We developed a prototype of a small, light,
      and wearable OT system that covers the entire forehead. We measured changes in
      the concentrations of oxy-Hb and deoxy-Hb in the prefrontal cortex while a
      subject performed a word fluency task. The results show typical changes in oxy-Hb
      and deoxy-Hb during the task and suggest that the prototype of our system can be
      used to investigate functions in the prefrontal cortex.

PMID- 19405664
TI  - Effects of anisotropic material property on the spring constant and the resonant
      frequency of atomic force microscope cantilever.
AB  - Atomic force microscope (AFM) is a powerful tool for force measurement in
      nanoscale. Many methods have been developed to obtain the precise cantilever's
      spring constant for improving the accuracy of force measurement. AFM cantilevers
      are usually made by single crystal silicon of which the anisotropic material
      property seriously affects the spring constant of cantilevers and has not
      considered before. In this paper, the density function theory was used to
      calculate the anisotropic stiffness matrix of crystal silicon, which was used in
      the finite element analysis to calculate lateral, axial, bending spring
      constants, and resonant frequencies of rectangular AFM cantilevers. These results
      were compared with those derived from other theoretical methods and with those
      provided by the manufacturers. The results showed that the anisotropic material
      property significantly affected the spring constants and the resonant frequencies
      of the AFM cantilever. The assumption of equivalent isotropic property of the
      rectangular AFM cantilever would cause an error up to 29.72%. Furthermore, two
      equations were proposed to obtain the spring constants and the resonant
      frequencies of crystal silicon AFM cantilever with the axis located at different
      cantilever-crystal angles.

PMID- 19405666
TI  - Tapping mode microwave impedance microscopy.
AB  - We report tapping mode microwave impedance imaging based on atomic force
      microscope platforms. The shielded cantilever probe is critical to localize the
      tip-sample interaction near the tip apex. The modulated tip-sample impedance can
      be accurately simulated by the finite-element analysis and the result agrees
      quantitatively to the experimental data on a series of thin-film dielectric
      samples. The tapping mode microwave imaging is also superior to the contact mode
      in that the thermal drift in a long time scale is totally eliminated and an
      absolute measurement on the dielectric properties is possible. We demonstrated
      tapping images on working nanodevices, and the data are consistent with the
      transport results.

PMID- 19405665
TI  - A system for high-resolution depth-resolved optical imaging of fluorescence and
      absorption contrast.
AB  - Laminar optical tomography (LOT) is a new three-dimensional in vivo functional
      optical imaging technique. Adopting a microscopy-based setup and diffuse optical
      tomography (DOT) imaging principles, LOT can perform both absorption- and
      fluorescence-contrast imaging with higher resolution (100-200 microm) than DOT
      and deeper penetration (2-3 mm) than laser scanning microscopy. These features,
      as well as a large field of view and acquisition speeds up to 100 frames per
      second, make LOT suitable for depth-resolved imaging of stratified tissues such
      as retina, skin, endothelial tissues and the cortex of the brain. In this paper,
      we provide a detailed description of a new LOT system design capable of imaging
      both absorption and fluorescence contrast, and present characterization of its
      performance using phantom studies.

PMID- 19405667
TI  - Frequency noise in frequency modulation atomic force microscopy.
AB  - Atomic force microscopy (AFM) using the frequency modulation (FM) detection
      method has been widely used for atomic/molecular-scale investigations of various
      materials. Recently, it has been shown that high-resolution imaging in liquids by
      the FM-AFM is also possible by reducing the noise-equivalent displacement in the
      cantilever displacement sensor and by oscillating the cantilever at a small
      amplitude even with the extremely reduced Q-factor due to the hydrodynamic
      interaction between the cantilever and the liquid. However, it has not been
      clarified how the noise reduction of the displacement sensor contributes to the
      reduction in the frequency noise in the FM-AFM in low-Q environments. In this
      article, the contribution of the displacement sensor noise to the frequency noise
      in the FM-AFM is described in detail to show how it is important to reduce the
      noise-equivalent displacement in the displacement sensor especially in low-Q
      environments.

PMID- 19405668
TI  - A control approach to cross-coupling compensation of piezotube scanners in
      tapping-mode atomic force microscope imaging.
AB  - In this article, an approach based on the recently developed inversion-based
      iterative control (IIC) to cancel the cross-axis coupling effect of piezoelectric
      tube scanners (piezoscanners) in tapping-mode atomic force microscope (AFM)
      imaging is proposed. Cross-axis coupling effect generally exists in piezoscanners
      used for three-dimensional (x-y-z axes) nanopositioning in applications such as
      AFM, where the vertical z-axis movement can be generated by the lateral x-y axes
      scanning. Such x/y-to-z cross-coupling becomes pronounced when the scanning is at
      large range and/or at high speed. In AFM applications, the coupling-caused
      position errors, when large, can generate various adverse effects, including
      large imaging and topography distortions, and damage of the cantilever probe
      and/or the sample. This paper utilizes the IIC technique to obtain the control
      input to precisely track the coupling-caused x/y-to-z displacement (with sign
      flipped). Then the obtained input is augmented as a feedforward control to the
      existing feedback control in tapping-mode imaging, resulting in the cancellation
      of the coupling effect. The proposed approach is illustrated through two
      exemplary applications in industry, the pole-tip recession examination, and the
      nanoasperity measurement on hard-disk drive. Experimental results show that the
      x/y-to-z coupling effect in large-range (20 and 45 microm) tapping-mode imaging
      at both low to high scan rates (2, 12.2 to 24.4 Hz) can be effectively removed.

PMID- 19405669
TI  - Thermionic emission and a novel electron collector in a liquid helium
      environment.
AB  - We study two techniques to create electrons in a liquid helium environment. One
      is thermionic emission of tungsten filaments in a low temperature cell in the
      vapor phase with a superfluid helium film covering all surfaces; the other is
      operating a glowing filament immersed in bulk liquid helium. We present both the
      steady state and rapid sweep I-V curves and the electron current yield. These
      curves, having a negative dynamic resistance region, differ remarkably from those
      of a vacuum tube filament. A novel low temperature vapor-phase electron collector
      for which the insulating helium film on the collector surface can be removed is
      used to measure emission current. We also discuss our achievement of producing
      multielectron bubbles in liquid helium by a new method.

PMID- 19405670
TI  - An apparatus for in situ x-ray scattering measurements during polymer injection
      molding.
AB  - We report a novel instrument for synchrotron-based in situ x-ray scattering
      measurements during injection molding processing. It allows direct, real-time
      monitoring of molecular-scale structural evolution in polymer materials
      undergoing a complex processing operation. The instrument is based on a
      laboratory-scale injection molding machine, and employs customized mold tools
      designed to allow x-ray access during mold filling and subsequent solidification,
      while providing sufficient robustness to withstand high injection pressures. The
      use of high energy, high flux synchrotron radiation, and a fast detector allows
      sufficiently rapid data acquisition to resolve time-dependent orientation
      dynamics in this transient process. Simultaneous monitoring of temperature and
      pressure signals allows transient scattering data to be referenced to various
      stages of the injection molding cycle. Representative data on a commercial liquid
      crystalline polymer, Vectra(R) B950, are presented to demonstrate the features of
      this apparatus; however, it may find application in a wide range of polymeric
      materials such as nanocomposites, semicrystalline polymers and fiber-reinforced
      thermoplastics.

PMID- 19405671
TI  - Phase sensitive Brillouin scattering measurements with a novel magneto-optic
      modulator.
AB  - A recently reported phase sensitive Brillouin light scattering technique is
      improved by use of a magnetic modulator. This modulator is based on Brillouin
      light scattering in a thin ferrite film. Using this magnetic modulator in time
      and space Brillouin light scattering measurements, we have increased phase
      contrast and excluded influence of optical inhomogeneities in the sample. We also
      demonstrate that the quality of the resulting interference patterns can be
      improved by data postprocessing using the simultaneously recorded information
      about the reference light.

PMID- 19405673
TI  - A setup combining magneto-optical Kerr effect and conversion electron Mossbauer
      spectrometry for analysis of the near-surface magnetic properties of thin films.
AB  - We propose a system allowing the characterization of thin magnetic multilayer
      structures that combine conversion electron Mossbauer spectrometry (CEMS) under
      applied magnetic field with the magneto-optical Kerr effect (MOKE) technique.
      Measured hysteresis loops obtained from the MOKE part are used for investigation
      of sample surface magnetic properties. The CEMS part of such a system is suitable
      for studying the spatial spin distribution during magnetization reversal under
      applied magnetic field, whose values are established from the measured MOKE loop.
      The combined technique is demonstrated on the results obtained at 300 K on an
      exchange-coupled ferrimagnetic amorphous GdFe/TbFe bilayer, where the center of
      the GdFe layer is enriched in (57)Fe. Both techniques confirm in-plane uniaxial
      anisotropy. The spin structure at the position of the probe layer is analyzed for
      several values of the external magnetic field applied in the hard magnetization
      axis direction.

PMID- 19405672
TI  - Absolute spin calibration of an electron spin polarimeter by spin-resolved
      photoemission from the Au(111) surface states.
AB  - Here we report the absolute characterization of a spin polarimeter by measuring
      the Sherman function with high precision. These results have been obtained from
      the analysis of the spin and angle-resolved photoemission spectra of Au(111)
      surface states. The measurements have been performed with a 250 kHz repetition
      rate Ti:sapphire amplified laser system combined with a high energy-, angle-, and
      spin-resolving time-of-flight electron spectrometer.

PMID- 19405674
TI  - Miniature diamond anvil cell for broad range of high pressure measurements.
AB  - A miniature versatile nonmagnetic diamond anvil cell for diverse physical
      property measurement under cryogenic environments and high magnetic fields at
      high pressure has been developed. Several such cells have been manufactured and
      tested in the Physical Properties Measurement System (PPMS) by Quantum Design at
      high pressures and low temperatures. The cells have good pressure stability
      during temperature scans down to helium temperatures and back to room
      temperature. The cells have been tested in strong magnetic fields and
      demonstrated excellent nonmagnetic properties. The wide-angle side openings give
      the possibility to use this cell as a "panoramic cell" in synchrotron experiments
      requiring large angle off-axis access. The possible experiments, which may use
      this cell, include spectroscopic experiments (optical, synchrotron Mossbauer,
      Raman, x-ray emission, etc.), different types of x-ray diffraction experiments,
      transport measurements (resistivity, magnetoresistivity, thermoelectromotive
      force, etc.), measurements of susceptibility, and many other conventional and
      synchrotron experiments at very low temperatures and in strong magnetic fields.

PMID- 19405675
TI  - Apparatus for probing preignition behavior of hypergolic materials.
AB  - The determination of the condensed-phase preignition chemistry of hypergolic
      bipropellant pairs has been considerably challenging due to toxicity and
      reactivity of the used materials. In this work, we describe a new experimental
      technique for characterizing preignition behavior of hypergolic materials. Small
      quantities of the bipropellant pair are brought in contact under isothermal
      conditions, and spectral transmission measurements on the evolved products are
      performed using Fourier transform infrared spectroscopy. The gaseous products are
      subsequently quantified to yield species concentration profiles at various
      temperatures, hence facilitating the elucidation of the detailed condensed-phase
      chemical kinetics responsible for the ignition in the gas phase.

PMID- 19405676
TI  - A new cavity based absorption instrument for detection of water isotopologues in
      the upper troposphere and lower stratosphere.
AB  - We describe here the Harvard integrated cavity output spectroscopy (ICOS) isotope
      instrument, a mid-IR infrared spectrometer using ICOS to make in situ
      measurements of the primary isotopologues of water vapor (H(2)O, HDO, and H(2)
      (18)O) in the upper troposphere and lower stratosphere (UTLS). The long path
      length provided by ICOS provides the sensitivity and accuracy necessary to
      measure these or other trace atmospheric species at concentrations in the ppbv
      range. The Harvard ICOS isotope instrument has been integrated onto NASA's WB-57
      high-altitude research aircraft and to date has flown successfully in four field
      campaigns from winter 2004-2005 to the present. Off-axis alignment and a fully
      passive cavity ensure maximum robustness against the vibrationally hostile
      aircraft environment. The very simple instrument design permitted by off-axis
      ICOS is also helpful in minimizing contamination necessary for accurate
      measurements in the dry UTLS region. The instrument is calibrated in the
      laboratory via two separate water addition systems and crosscalibrated against
      other instruments. Calibrations have established an accuracy of 5% for all
      species. The instrument has demonstrated measurement precision of 0.14 ppmv, 0.10
      ppbv, and 0.16 ppbv in 4 s averages for H(2)O, HDO, and H(2) (18)O, respectively.
      At a water vapor mixing ratio of 5 ppmv the isotopologue ratio precision is
      50[per thousand] and 30[per thousand] for deltaD and delta(18)O, respectively.

PMID- 19405677
TI  - Single-scan measurement of conductance of a quartz crystal microbalance array
      coupled with resonant markers for biosensing in liquid phase.
AB  - This work presents a method for sensing the viscoelastic property of liquid/solid
      interface using a quartz crystal microbalance (QCM) array. Each sensor in a QCM
      array has a unique resonant frequency and can be identified by a single-scan
      measurement of admittance (or impedance). The resonant frequency encoding at each
      sensor in an array was realized by connecting a capacitor with a known
      capacitance, called a resonant marker, to the sensor in series. Changes in the
      resonant frequency of all sensors in an array can be determined using an
      impedance analyzer and a program that determines the frequencies at which the
      conductance is at a local maximum. The sensing method allows every sensor output
      (resonant frequency) to be obtained without the use of time-consuming multiplexed
      hardware and software. Adsorptions of biomolecules by multiple sensor are
      monitored in the liquid phase to demonstrate the feasibility of frequency
      encoding using resonant markers and the single-scan measurement of conductance of
      a QCM array.

PMID- 19405678
TI  - Construction of an integrated Raman- and angular-scattering microscope.
AB  - We report on the construction of a multimodal microscope platform capable of
      gathering both elastically and inelastically scattered light from a 38 mum(2)
      region in both epi- and transillumination geometries. Simultaneous monitoring of
      elastic and inelastic scattering from a microscopic region allows noninvasive
      characterization of the chemistry and morphology of a living sample without the
      need for exogenous dyes or labels, thus allowing measurements to be made
      longitudinally in time on the same sample as it evolves naturally. A sample is
      illuminated either from above or below with a focused 785 nm TEM(00) mode laser
      beam, with elastic and inelastic scattering collected by two separate measurement
      arms. The measurements may be made either simultaneously, if identical
      illumination geometries are used, or sequentially, if the two modalities utilize
      opposing illumination paths. In the inelastic arm, Stokes-shifted light is
      dispersed by a spectrograph onto a charge-coupled device (CCD) array. In the
      elastic scattering collection arm, a relay system images the microscope's back
      aperture onto a CCD array. Postprocessing of the inelastic scattering to remove
      fluorescence signals yields high quality Raman spectra that report on the
      sample's chemical makeup. Comparison of the elastically scattered pupil images to
      generalized Lorenz-Mie theory yields estimated size distributions of scatterers
      within the sample.

PMID- 19405679
TI  - Autonomous low-power magnetic data collection platform to enable remote high
      latitude array deployment.
AB  - A major driver in the advancement of geophysical sciences is improvement in the
      quality and resolution of data for use in scientific analysis, discovery, and for
      assimilation into or validation of empirical and physical models. The need for
      more and better measurements together with improvements in technical capabilities
      is driving the ambition to deploy arrays of autonomous geophysical instrument
      platforms in remote regions. This is particularly true in the southern polar
      regions where measurements are presently sparse due to the remoteness, lack of
      infrastructure, and harshness of the environment. The need for the acquisition of
      continuous long-term data from remote polar locations exists across geophysical
      disciplines and is a generic infrastructure problem. The infrastructure, however,
      to support autonomous instrument platforms in polar environments is still in the
      early stages of development. We report here the development of an autonomous low
      power magnetic variation data collection system. Following 2 years of field
      testing at the south pole station, the system is being reproduced to establish a
      dense chain of stations on the Antarctic plateau along the 40 degrees magnetic
      meridian. The system is designed to operate for at least 5 years unattended and
      to provide data access via satellite communication. The system will store 1 s
      measurements of the magnetic field variation (<0.2 nT resolution) in three vector
      components plus a variety of engineering status and environment parameters. We
      believe that the data collection platform can be utilized by a variety of low
      power instruments designed for low-temperature operation. The design, technical
      characteristics, and operation results are presented here.

PMID- 19405680
TI  - Microwave phase detection at the level of 10(-11) rad.
AB  - We report on a noise measurement system with the highest spectral resolution ever
      achieved in the microwave domain. It is capable of detecting the phase
      fluctuations in rms amplitude of 2x10(-11) rad/sqrt Hz at Fourier frequencies
      above a few kilohertz. Such precision allows the study of intrinsic fluctuations
      in various microwave components and materials, as well as precise tests of
      fundamental physics. Employing this system we discovered a previously unknown
      phenomenon of down-conversion of pump oscillator phase noise into the low
      frequency voltage fluctuations.

PMID- 19405681
TI  - Matched wideband low-noise amplifiers for radio astronomy.
AB  - Two packaged low noise amplifiers for the 0.3-4 GHz frequency range are
      described. The amplifiers can be operated at temperatures of 300-4 K and achieve
      noise temperatures in the 5 K range (<0.1 dB noise figure) at 15 K physical
      temperature. One amplifier utilizes commercially available, plastic-packaged SiGe
      transistors for first and second stages; the second amplifier is identical except
      it utilizes an experimental chip transistor as the first stage. Both amplifiers
      use resistive feedback to provide input reflection coefficient S11<-10 dB over a
      decade bandwidth with gain over 30 dB. The amplifiers can be used as rf
      amplifiers in very low noise radio astronomy systems or as i.f. amplifiers
      following superconducting mixers operating in the millimeter and submillimeter
      frequency range.

PMID- 19405682
TI  - Apparatus and method to measure dielectric properties (epsilon(') and epsilon("))
      of ionic liquids.
AB  - Conventional techniques for measurement of dielectric properties of ionic liquids
      or electrolyte solutions fail because the samples are largely short circuited by
      the high electrical conductance. The object of the author's research activity was
      to elaborate an apparatus (microwave dielectrometer) and method suitable to
      measure the dielectric constant (epsilon(')) and loss factor (epsilon(")) of well
      conducting ionic liquids and other solvents. This process is based on a revised
      waveguide method completed with an automatic calibration possibility. Contrary to
      conventional measuring methods this technique uses about 20 W/g power density.
      The measurements were carried out at 2.45 GHz frequency in the temperature range
      from 10 up to 100 degrees C. The obtained (epsilon(')) and (epsilon(")) values of
      different solvents were compared with several published (calculated and measured)
      data. Statistical analysis was used to determine the error of measurements and
      distilled water was chosen as a standard for study of data dispersion. To
      accomplish statistical analysis, namely, the dielectric characteristics have to
      be determined at the same temperature. The values of variances were less or equal
      1 in case of epsilon(') and decrease with increasing temperature. In case of
      epsilon(") the variance data were much smaller.

PMID- 19405683
TI  - Measurement of urinary calcium using AT89C51RD2 microcontroller.
AB  - A simple and inexpensive absorption technique for determination of calcium ion in
      urine samples is developed, comprising a light emitting diode (650 nm) as the
      light source and photodiode as the detector with AT89C51RD2 microcontroller. The
      design of the system and details of interface, calibration, and procedure of
      operation are explained in this paper. Software is developed to monitor sample
      processing and to display the results in liquid crystal display screen. With 15
      microl sample volume, a linear output is obtained in the range of 2.5-7.5 mM
      calcium with a detection limit of 0.06 mM. Interferences from other cations such
      as monovalent ion and divalent ion are investigated in the expected range, which
      are normally present in clinical samples, and absorption changes over the pH
      range of 3-12 are also determined. This system has been demonstrated successfully
      for the successive assay of calcium in urine samples, with the results comparing
      well to those achieved and in good agreement with values obtained with the
      current clinical spectrophotometric method at 95% of confidence level.

PMID- 19405684
TI  - Magnetic-field cycling instrumentation for dynamic nuclear polarization-nuclear
      magnetic resonance using photoexcited triplets.
AB  - To advance static solid-state NMR with hyperpolarized nuclear spins, a system has
      been developed enabling dynamic nuclear polarization (DNP) using electron spins
      in the photoexcited triplet state with X-band microwave apparatus, followed by
      static solid-state nuclear magnetic resonance (NMR) experiments using the
      polarized nuclear-spin system with a goniometer. In order to perform the DNP and
      NMR procedures in different magnetic fields, the DNP system and the NMR system
      are spatially separated, between which the sample can be shuttled while its
      orientation is controlled in a reproducible fashion. We demonstrate that the
      system developed in this work is operational for solid-state NMR with
      hyperpolarized nuclear-spin systems in static organic materials, and also discuss
      the application of our system.

PMID- 19405685
TI  - Dose profile measurement using an imaging plate: Evaluation of filters using
      Monte Carlo simulation of 4 MV x-rays.
AB  - Computed radiography (CR) is gradually replacing film. The application of CR for
      two-dimensional profiles and off-axis ratio (OAR) measurement using an imaging
      plate (IP) in a CR system is currently under discussion. However, a well known
      problem for IPs in dosimetry is that they use high atomic number (Z) materials,
      such as Ba, which have an energy dependency in a photon interaction. Although
      there are some reports that it is possible to compensate for the energy
      dependency with metal filters, the appropriate thicknesses of these filters and
      where they should be located have not been investigated. The purpose of this
      study is to find the most suitable filter for use with an IP as a dosimetric
      tool. Monte Carlo simulation (Geant4 8.1) was used to determine the filter to
      minimize the measurement error in OAR measurements of 4 MV x-rays. In this
      simulation, the material and thickness of the filter and distance between the IP
      and the filter were varied to determine most suitable filter conditions that gave
      the best fit to the MC calculated OAR in water. With regard to changing the
      filter material, we found that using higher Z and higher density material
      increased the effectiveness of the filter. Also, increasing the distance between
      the filter and the IP reduced the effectiveness, whereas increasing the thickness
      of the filter increased the effectiveness. The result of this study showed that
      the most appropriate filter conditions consistent with the calculated OAR in
      water were the ones with the IP sandwiched between two 2 mm thick lead filters at
      a distance of 5 mm from the IP or the IP sandwiched directly between two 1 mm
      lead filters. Using these filters, we measured the OAR at 10 cm depth with 100 cm
      source-to-surface distance and surface 10x10 cm(2) field size. The results of
      this measurement represented that it is possible to achieve measurements with
      less than within 2.0% and 2.0% in the field and with less than 1.1% and 0.6% out
      of the field by using 2 and 1 mm lead filters, respectively.

PMID- 19405686
TI  - A strategy to eliminate all nonlinear effects in constant-voltage hot-wire
      anemometry.
AB  - A constant-voltage anemometer is subject to nonlinear effects when the operating
      hot wire is exposed to large velocity fluctuations in the incident flow. This
      results in the generation of undesirable higher harmonics, just as in the two
      classic systems, constant-current and constant-temperature anemometers, for which
      no attempts are normally made to correct the nonlinearities. The present
      investigation shows that these undesirable higher harmonics can be suppressed in
      the case of a constant-voltage anemometer. A new approach to process experimental
      data is proposed. It is based on three explicit equations established and solved
      with all terms included, i.e., without linearization. These are (1) the first
      order differential equation that describes the electronic circuit of a constant
      voltage anemometer-this equation permits to deduce the instantaneous resistance
      of the hot wire from the output voltage of the anemometer; (2) the first-order
      differential equation that expresses the thermal lag behavior of the hot wire
      when used in a constant-voltage mode-this equation permits to restore the
      instantaneous resistance that an ideal wire would have without thermal inertia in
      the same flow conditions; and (3) the algebraic relation that expresses the heat
      transfer law of an ideal wire, according to King's law, a look-up table, or a
      polynomial fit-this relation permits to deduce the instantaneous flow velocity
      from the instantaneous resistance of the ideal wire. The proposed method is
      easily implemented on a personal computer and permits odd turbulence moments,
      such as skewness factors, to be obtained satisfactorily.

PMID- 19405687
TI  - Portable laser-heating stand for synchrotron applications.
AB  - A compact, double-sided laser-heating system for diamond-cell synchrotron
      applications is described. The optical table, containing laser, spectrometer, and
      all optics for visual observation and measuring temperatures and pressures has an
      area of less than 1/2 m(2) and weighs less than 20 kg. All components can be
      remotely controlled at micron levels with simple dc motors and pneumatic drives.
      The design allows quick alignment of the laser-heated hot spot with the x-ray
      beam and the spectrometer. The prealigned system can be set up at most
      synchrotron beamlines within about 1 h. We carried out measurements on a variety
      of materials above one megabar and up to over 4000 K at both the x-ray
      diffraction beamline ID 27 and the x-ray absorption beamline ID 24 at the
      European Synchrotron Facility. A new measurement of the melting temperature of
      iron by x-ray absorption spectroscopy is presented.

PMID- 19405688
TI  - Friction models incorporating thermal effects in highly precision actuators.
AB  - This paper presents two models based on the LuGre model for friction with
      consideration of thermal effects. In Model I, parameters in the LuGre model are
      considered as temperature dependent. In Model II, parameters in the LuGre model
      are considered as temperature independent; while a temperature-dependent function
      is added to the temperature-independent LuGre model. Both models are
      experimentally evaluated, which shows that both can effectively incorporate
      thermal effects but Model II has better accuracy. Since these models are
      developed in the context of the motion system, they should be readily
      incorporated in motion control algorithms for effective control of motion systems
      with friction if temperature rise is significant in these systems.

PMID- 19405689
TI  - An iterative curve fitting method for accurate calculation of quality factors in
      resonators.
AB  - A new method for eliminating the noise effect in interpreting the measured
      magnitude transfer characteristic of a resonator, in particular in extracting the
      Q-factor, is proposed and successfully tested. In this method the noise
      contribution to the measured power spectral density of resonator is iteratively
      excluded through a sequence of least-square curve fittings. The advantage of the
      presented method becomes more tangible when the signal to noise power ratio (SNR)
      is close to unity. A set of experiments for a resonant cantilever vibrating at
      different amplitudes has shown that when SNR is less than 10, the calculation
      results of conventional methods in extracting the Q-factor, i.e., the 3 dB
      bandwidth and single least-square curve fit, exhibit significant deviations from
      the actual Q-factor, while the result of the proposed iterative method remains in
      5% margin of error even for a SNR of unity. This method is especially useful when
      no specific data is available about the measurement noise, except the assumption
      that the noise spectral density is constant over the measured bandwidth.

PMID- 19405690
TI  - A new magnetic bearing using Halbach magnet arrays for a magnetic levitation
      stage.
AB  - Next-generation lithography requires a high precision stage, which is compatible
      with a high vacuum condition. A magnetic levitation stage with six degrees-of
      freedom is considered state-of-the-art technology for a high vacuum condition.
      The noncontact characteristic of magnetic levitation enables high precision
      positioning as well as no particle generation. To position the stage against
      gravity, z-directional electromagnetic levitation mechanisms are widely used.
      However, if electromagnetic actuators for levitation are used, heat is inevitably
      generated, which deforms the structures and degrades accuracy of the stage. Thus,
      a gravity compensator is required. In this paper, we propose a new magnetic
      bearing using Halbach magnet arrays for a magnetic levitation stage. The novel
      Halbach magnetic bearing exerts a force four times larger than a conventional
      magnetic bearing with the same volume. We also discuss the complementary
      characteristics of the two magnetic bearings. By modifying the height of the
      center magnet in a Halbach magnetic bearing, a performance compromise between
      levitating force density and force uniformity is obtained. The Halbach linear
      active magnetic bearing can be a good solution for magnetic levitation stages
      because of its large and uniform levitation force.

PMID- 19405691
TI  - A smart microfour-point probe with ultrasharp in-plane tips.
AB  - We propose a smart microfour-point probe (micro4PP) with ultrasharp in-plane tips
      that are arranged in a square with a spacing of 20 microm. The micro4PP consists
      of a supporting cantilever and four subcantilevers. The subcantilevers are
      symmetrically suspended from the square frame at the end of the supporting
      cantilever. A thermal actuator based on the bimorph effect is also integrated on
      each subcantilever for functionalization of interest. The unique configuration of
      the four-terminal tips is very useful for versatile applications of the micro4PP.

PMID- 19405692
TI  - Magnetic force driven six degree-of-freedom active vibration isolation system
      using a phase compensated velocity sensor.
AB  - A six-axis active vibration isolation system (AVIS) is developed using voice coil
      actuators. Point contact configuration is employed to have an easy assembly of
      eight voice coil actuators to an upper and a base plates. The velocity sensor,
      using an electromagnetic principle that is commonly used in the vibration
      control, is investigated since its phase lead characteristic causes an
      instability problem for a low frequency vibration. The performances of the AVIS
      are investigated in the frequency domain and finally validated by comparing with
      the passive isolation system using the atomic force microscope images.

PMID- 19405693
TI  - Nanoposition sensors with superior linear response to position and unlimited
      travel ranges.
AB  - With the advancement in nanotechnology, the ability of positioning/measuring at
      subnanometer scale has been one of the most critical issues for the
      nanofabrication industry and researchers using scanning probe microscopy.
      Commercial nanopositioners have achieved direct measurements at the scale of 0.01
      nm with capacitive sensing metrology. However, the commercial sensors have small
      dynamic ranges (up to only a few hundred micrometers) and are relatively large in
      size (centimeters in the transverse directions to the motion), which is necessary
      for healthy signal detections but making it difficult to use on smaller devices.
      This limits applications in which large materials (on the scale of centimeters or
      greater) are handled with needs of subnanometer resolutions. What has been done
      in the past is to combine the fine and coarse translation stages with different
      dynamic ranges to simultaneously achieve long travel range and high spatial
      resolution. In this paper, we present a novel capacitive position sensing
      metrology with ultrawide dynamic range from subnanometer to literally any
      practically desired length for a translation stage. This sensor will greatly
      simplify the task and enhance the performance of direct metrology in a hybrid
      translational stage covering translation tasks from subnanometer to centimeters.

PMID- 19405694
TI  - Nondestructive detection of hidden chemical compounds with laser Compton
      scattering gamma rays.
AB  - A nondestructive assay method for measuring a shielded chemical compound has been
      proposed. The chemical compound is measured by using a nuclear resonance
      fluorescence (NRF) measurement technique with an energy tunable laser Compton
      scattering (LCS) gamma-ray source. This method has an advantage that hidden
      materials can be detected through heavy shields such as iron plates of a
      thickness of several centimeters. A detection of a chemical compound of melamine,
      C(3)H(6)N(6), shielded by 15-mm-thick iron and 4-mm-thick lead plates is
      demonstrated. The NRF gamma-rays of (12)C and (14)N of the melamine are measured
      by using the LCS gamma-rays of the energies of up to 5.0 MeV. The observed ratio
      ((12)C/(14)N)(exp)=0.39+/-0.12 is consistent with (C/N)(melamine)=0.5.

PMID- 19405695
TI  - Design and implementation of a system with a multielement thermopile for
      monitoring temperature of a plane.
AB  - In this paper, we report the design of a system equipped with a multielement
      thermopile for measuring the temperature of a given plane. We evaluate the
      performance of our measurement system, which comprises a microcontroller, an
      analog-to-digital converter, a liquid crystal display (LCD), light-emitting
      diodes (LEDs), a buzzer, laser pointers, and a rotary encoder. We use different
      types of display modes such as an LCD for displaying the measured temperature,
      LEDs which colors indicate the temperature range, and an RS-232 or a wireless
      interface that transmits the temperature values to be displayed as different
      colors on a PC screen. The buzzer/alarm in the system is activated when the
      threshold temperature is reached. The system is inexpensive, portable, and can be
      used for two-dimensional temperature measurements; further, its emissivity can be
      easily adjusted. The effective detection range of this system is from -20 to 115
      degrees C, and the field of view is 41 degrees x32 degrees ; the measurement
      error is confined to +/-1 degrees C. The experimental results demonstrate the
      effectiveness of the system in monitoring the temperature of a remote plane.
      Hence, it is possible to identify a hot spot that occurred in the electrical
      heating equipment or a smoldering source hidden in upholstery.

PMID- 19405696
TI  - A novel method for preparing stoichiometric SnO(2) thin films at low temperature.
AB  - Tin oxide is a well known nonstoichiometric material with dual valency. The
      invariance of stoichiometry is very intriguing. As of today no report is
      available for preparing perfect stoichiometric tin oxide. Here we report a novel
      method to prepare stoichiometric tin oxide by modifying the known plasma enhanced
      chemical vapor deposition technique using SnCl(4)-xH(2)O as precursor and O(2) as
      reactant gas at various temperatures from 300 to 800 degrees C. Tetragonal rutile
      structure of SnO(2) was found, grown along the [110] direction. X-ray
      photoelectron spectroscopic measurement showed constant Sn/O ratio. Sn 3d and O
      1s were found composed of only Sn(4+) (487.2 eV) and O-Sn(4+) (531.2 eV) with
      equal peak widths. Raman band intensity ( approximately 633 cm(-1)) was found
      increasing with temperature, indicating the morphological changes. Sheet
      resistance of approximately 0.5 kOmega/at 300 degrees C was measured that reduces
      to approximately 0.1 kOmega/at 600 degrees C. It is found that film stoichiometry
      remains unaltered, while the structural morphology changes significantly.

PMID- 19405697
TI  - High performance diffuse reflectance circular dichroism spectrophotometer.
AB  - A new dual-purpose transmittance circular dichroism (CD) and diffuse reflectance
      CD (DRCD) universal chiroptical spectrophotometer (UCS-3, J-800KCMFII) was
      successfully developed to have the capability of measuring DRCD spectra down to
      190 nm with high efficiency, based on UCS-2: J-800KCMF. Optical components newly
      used in UCS-3 are the integrating sphere of optimum size and material to achieve
      high performance particularly in the shorter wavelength region, a baffle
      installed to reduce the first specular reflection signals, and a condenser lens
      to increase light intensity per area for small samples. As a result, UCS-3 has
      become a very powerful instrument to measure DRCD spectra of powdered samples in
      situ, with approximately 20 times sensitivity of existing UCS-2. We could show
      that to achieve similar quality DRCD spectra, only 50 mug of (S)-(+)-1,1(')
      binaphthyl-2,2(')-diyl hydrogen phosphate is required on UCS-3, as compared with
      1.12 mg for UCS-2.

PMID- 19405698
TI  - Characterizing piezoscanner hysteresis and creep using optical levers and a
      reference nanopositioning stage.
AB  - A method using atomic force microscope (AFM) optical levers and a reference
      nanopositioning stage has been developed to characterize piezoscanner hysteresis
      and creep. The piezoscanner is fixed on a closed-loop nanopositioning stage, both
      of which have the same arrangement on each axis of the three spatial directions
      inside the AFM-based nanomanipulation system. In order to achieve
      characterization, the optical lever is used as a displacement sensor to measure
      the relative movement between the nanopositioning stage and the piezoscanner by
      lateral tracking a well-defined slope with the tapping mode of the AFM
      cantilever. This setup can be used to estimate a piezoscanner's voltage input
      with a reference displacement from the nanopositioning stage. The hysteresis and
      creep were accurately calibrated by the method presented, which use the current
      setup of the AFM-based nanomanipulation system without any modification or
      additional devices.

PMID- 19405700
TI  - X-ray- and electron-induced infrared emission spectroscopy.
AB  - We demonstrate the use of Fourier transform infrared (IR) spectroscopy for
      midinfrared emission measurements following x-ray or electron excitation. Spectra
      from an InAs low band-gap semiconductor film, which emits in the IR from 3000 to
      3400 cm(-1), are presented. There is good agreement between the present results
      and previously published laser-excited spectra. Using focused beams, it should be
      possible to perform sub-diffraction-limited IR imaging. In addition, simultaneous
      structural and electronic analysis could be performed using the x-ray or electron
      excitation probes.

PMID- 19405699
TI  - Small angle x-ray scattering with a beryllium compound refractive lens as
      focusing optic.
AB  - At BW4 at HASYLAB a beryllium compound refractive lens (Be-CRL) is used for the
      focusing in small-angle x-ray scattering experiments. Using it provides the
      advantages of higher long-term stability and a much easier alignment compared to
      a setup with focusing mirrors. In our investigations presented here, we show the
      advantages of using a Be-CRL in small-angle and also ultra small-angle x-ray
      scattering. We investigated the beam characteristics at the sample position with
      respect to spot size and photon flux. The spot size is comparable to that of a
      setup with focusing mirrors but with a gain in flux and better long-term
      stability. It is also shown that plane mirrors are still necessary to suppress
      higher order energies passing the monochromator.

PMID- 19405701
TI  - A 2.8 K cryogen-free cryostat with compact optical geometry for multiple photon
      counting.
AB  - Interest in solid scintillators down to liquid helium temperature and below has
      grown recently, fuelled by searches for exotic processes in particle physics. We
      describe a closed-cycle optical cryostat with a 2.8 K base temperature and a
      compact optical geometry for multiple photon counting. The large numerical
      aperture achieved, of the order of 0.79 from the optical center to each of the
      two windows and amounting to 40% of the total solid angle, allows a significant
      gain in the efficiency of photon collection. This and the relatively big sample
      size that can be used facilitate the study of scintillators under gamma
      irradiation. These features should be an asset for multiple photon counting
      techniques at low temperatures.

PMID- 19405702
TI  - Quantitative optical recognition of highly reproducible ultrathin oxide films in
      microelectrochemical anodization.
AB  - Automatized microelectrochemical investigations are achieved using a scanning
      droplet cell. The area reproducibility for a 100 mum oxide spot is found to be
      better than 1%, a value typically difficult to reach even in macroscopic samples.
      A systematic change in color appearance is seen for oxide films with a thickness
      ranging from 14 to 27 nm. Analysis of optical images yields a strictly linear
      relation between relative transmission and anodization charge and thus allows
      determination of the oxide thickness with a remarkable precision better than 0.5
      nm at an absolute film thickness value that is at least a factor of 20 smaller
      than the wavelength of light.

PMID- 19405703
TI  - Determination of energy band gap of nanocrystalline SbSI using diffuse
      reflectance spectroscopy.
AB  - Twelve methods of determining energy band gap (E(g)) of semiconductors using
      diffuse reflectance spectroscopy have been applied in investigations of
      sonochemically produced antimony sulfoiodide (SbSI) consisting of nanowires. It
      has been proved that the best method of determining E(g) is based on simultaneous
      fitting of many mechanisms of absorption to the spectral dependence of Kubelka
      Munk function evaluated from the diffuse reflectance data. It allows determining
      the values of indirect forbidden E(g), the Urbach energy, and the constant
      absorption/scattering of the examined semiconductor.

PMID- 19405704
TI  - A variable torque motor compatible with magnetic resonance imaging.
AB  - High magnetic fields used in magnetic resonance imaging (MRI) do not allow the
      employment of conventional motors due to various incompatibility issues. This
      paper reports on a new motor that can operate in or near high field magnets used
      for MRI. The motor was designed to be operational with the MRI equipment and
      could be used in a rotating imaging gantry inside the magnet designed for dual
      modality imaging. Furthermore, it could also be used for image guided robotic
      interventional procedures inside a MRI system if so desired. The prototype motor
      was developed using magnetic resonance (MR) compatible materials, and its
      functionality with MR imaging was evaluated experimentally by measuring the
      performance of the motor and its effect on the MR image quality. Since in our
      application, namely, single photon emission tomography, the motor has to perform
      precise stepping of the gantry in small angular steps the most important
      parameter is the start-up torque. The experimental results showed that the motor
      has a start-up torque up to 1.37 Nm and rotates at 196 rpm when a constant
      voltage difference of 12 V is applied at a magnetic field strength of 1 T. The MR
      image quality was quantified by measuring the signal-to-noise of images acquired
      under different conditions. The results presented here indicate that the motor is
      MR compatible and could be used for rotating an imaging gantry or a surgical
      device inside the magnet.

PMID- 19405705
TI  - Comment on "Generation of cold low divergent atomic beam of indium by laser
      ablation" [Rev. Sci. Instrum. 76, 113302 (2005)].
AB  - We present measurements of the velocity distribution of calcium atoms in an
      atomic beam generated using a dual-stage laser back-ablation apparatus.
      Distributions are measured using a velocity selective Doppler time-of-flight
      technique. They are Boltzmann-like with rms velocities corresponding to
      temperatures above the melting point for calcium. Contrary to a recent report in
      the literature, this method does not generate a subthermal atomic beam.

PMID- 19405708
TI  - Noninvasive, in vivo imaging of blood-oxygenation dynamics within the mouse brain
      using photoacoustic microscopy.
AB  - Photoacoustic microscopy (PAM) has been used to obtain high-resolution,
      noninvasive images of the in vivo mouse brain. In this work, we exploit the high
      depth and temporal resolutions of PAM to noninvasively image the blood
      oxygenation dynamics of multiple cortex vessels in the mouse brain simultaneously
      in response to controlled hypoxic and hyperoxic challenges. These results confirm
      the ability of PAM to track blood oxygenation in the mouse brain, a critical
      aspect of imaging brain activity through the hemodynamic response.

PMID- 19405709
TI  - Extracting diagnostic stromal organization features based on intrinsic two-photon
      excited fluorescence and second-harmonic generation signals.
AB  - Intrinsic two-photon excited fluorescence (TPEF) and second-harmonic generation
      (SHG) signals are shown to differentiate between normal and neoplastic human
      esophageal stroma. It was found that TPEF and SHG signals from normal and
      neoplastic stroma exhibit different organization features, providing quantitative
      information about the biomorphology and biochemistry of tissue. By comparing
      normal with neoplastic stroma, there were significant differences in collagen
      related changes, elastin-related changes, and alteration in proportions of matrix
      molecules, giving insight into the stromal changes associated with cancer
      progression and providing substantial potential to be applied in vivo to the
      clinical diagnosis of epithelial precancers and cancers.

PMID- 19405707
TI  - Dynamic noninvasive monitoring of renal function in vivo by fluorescence lifetime
      imaging.
AB  - Kidneys normally filter the blood of excess salts and metabolic products, such as
      urea, while retaining plasma proteins. In diseases such as multiple myeloma and
      diabetes mellitus, the renal function is compromised and protein escapes into the
      urine. In this study, we present the use of fluorescence lifetime imaging (FLI)
      to image excess serum protein in urine (proteinuria). The near-infrared
      fluorescent dye LS-288 has distinct lifetimes when bound to protein versus free
      in solution, providing contrast between the protein-rich viscera and the mostly
      protein-free bladder. FLI with LS-288 in mice revealed that fluorescence lifetime
      (FLT) differences in the bladder relative to surrounding tissues was due to the
      fractional contributions of the bound and unbound dye molecules. The FLT of LS
      288 decreased in the case of proteinuria while fluorescence intensity was
      unchanged. The results show that FLI can be useful for the dynamic imaging of
      protein-losing nephropathy due to diabetes mellitus and other renal diseases and
      suggest the potential use of the FLI to distinguish tumors from fluid-filled
      cysts in the body.

PMID- 19405710
TI  - Evaluation of the contribution of the renal capsule and cortex to kidney
      autofluorescence intensity under ultraviolet excitation.
AB  - The use of reduced nicotinamide adenine dinucleotide (NADH) fluorescence to gain
      metabolic information on kidneys in response to an alteration in oxygen
      availability has previously been experimentally demonstrated, but signal
      quantification has not, to date, been addressed. In this work the relative
      contribution to rat kidney autofluorescence of the capsule versus cortex under
      ultraviolet excitation is determined from experimental results obtained using
      autofluorescence microscopy and a suitable mathematical model. The results allow
      for a quantitative assessment of the relative contribution of the signal
      originating in the metabolically active cortex as a function of capsule thickness
      for different wavelengths.

PMID- 19405711
TI  - Calibration and validation of an optical sensor for intracellular oxygen
      measurements.
AB  - Calibration of fluorescent optical sensors for accurate, quantitative
      intracellular measurements in vivo suffers from lack of a representative medium
      that appropriately simulates the molecular complexity of the cytosol. We present
      a novel protocol for accurate intracellular oxygen sensing via fluorescence
      lifetime imaging microscopy (FLIM) using cell lysate-FLIM measurements to correct
      the in vitro calibration of a fluorescent oxygen sensor, and we describe electron
      paramagnetic resonance (EPR) validation studies. Lysate-FLIM studies provided
      biochemical information, while EPR provided a "gold standard" for intracellular
      oxygen estimation. Oxygen levels were evaluated in living human normal squamous
      and adenocarcinoma esophageal epithelial cells, and good agreement was observed
      between oxygen levels derived from the optical protocol and EPR. The proposed
      protocol introduces the concept of a living cell line as a reference for
      estimating unknown oxygen levels in other cell lines and accounts for high
      degrees of variability between different cell lines.

PMID- 19405712
TI  - Dynamic topographic mapping of the human bladder during voiding using functional
      near-infrared spectroscopy.
AB  - Functional near-infrared spectroscopy (fNIRS) with multichannel instruments and
      grids of source-detector pairs can map regional change in
      oxygenation/hemodynamics. Developed for cortical brain mapping, fNIRS technology
      has relevance in other organs where pathology affects the microcirculation. We
      describe fNIRS of the human bladder for evaluation of hemodynamic change during
      voiding. A 5x5-cm grid with two source-detector pairs is placed on the abdomen
      suprapubically in an asymptomatic male. In four separate trials, after natural
      bladder filling NIRS-derived changes in oxyhemoglobin (O(2)Hb), deoxyhemoglobin
      (HHb), and total hemoglobin (tHb) concentration are recorded during voiding
      (measured via uroflow), using four channels of a four wavelength continuous wave
      instrument. Graphic and video images (topographic mapping software) are
      generated. Changes in tHb occur following permission to void that predominantly
      reflected variation in O(2)Hb; tHb peaks at maximum urine flow then falls to a
      nadir lasting to uroflow end. Change in fNIRS video color intensity correlates
      with graphic change in chromophore concentration. Color variations across the
      mapped area suggest regional hemodynamic variation. fNIRS bladder studies
      generate reproducible chromophore data consistent with single channel studies,
      but the dynamic color video and larger tissue area monitored potentially offer
      new methodology for investigating regional variations in bladder oxygenation and
      hemodynamics.

PMID- 19405714
TI  - Strategy of topical vaccination with nanoparticles.
AB  - Liposomes in the nanosize range have been recognized as a versatile drug delivery
      system of both hydrophilic and lipophilic molecules. In order to develop a
      liposome-based topical vaccination strategy, five different types of liposomes
      were tested as a putative vaccine delivery system on pig ear skin. The
      investigated liposomes mainly varied in size, lipid composition, and surface
      charge. Using hydrophilic and hydrophobic fluorescent dyes as model drugs,
      penetration behavior was studied by means of confocal laser scanning microscopy
      of intact skin and histological sections, respectively. Follicular penetration of
      the liposomes was measured in comparison to a standard, nonliposomal formulation
      at different time points. Dependent on time but independent of their different
      characters, the liposomes showed a significantly higher penetration depth into
      the hair follicles compared to the standard formulation. The standard formulation
      reached a relative penetration depth of 30% of the full hair follicle length
      after seven days, whereas amphoteric and cationic liposomes had reached
      approximately 70%. Penetration depth of negatively charged liposomes did not
      exceed 50% of the total follicle length. The fluorescence dyes were mainly
      detected in the hair follicle; only a small amount of dye was found in the upper
      parts of the epidermis.

PMID- 19405715
TI  - Automated detection and analysis of fluorescent in situ hybridization spots
      depicted in digital microscopic images of Pap-smear specimens.
AB  - Fluorescence in situ hybridization (FISH) technology has been widely recognized
      as a promising molecular and biomedical optical imaging tool to screen and
      diagnose cervical cancer. However, manual FISH analysis is time-consuming and may
      introduce large inter-reader variability. In this study, a computerized scheme is
      developed and tested. It automatically detects and analyzes FISH spots depicted
      on microscopic fluorescence images. The scheme includes two stages: (1) a feature
      based classification rule to detect useful interphase cells, and (2) a knowledge
      based expert classifier to identify splitting FISH spots and improve the accuracy
      of counting independent FISH spots. The scheme then classifies detected
      analyzable cells as normal or abnormal. In this study, 150 FISH images were
      acquired from Pap-smear specimens and examined by both an experienced
      cytogeneticist and the scheme. The results showed that (1) the agreement between
      the cytogeneticist and the scheme was 96.9% in classifying between analyzable and
      unanalyzable cells (Kappa=0.917), and (2) agreements in detecting normal and
      abnormal cells based on FISH spots were 90.5% and 95.8% with Kappa=0.867. This
      study demonstrated the feasibility of automated FISH analysis, which may
      potentially improve detection efficiency and produce more accurate and consistent
      results than manual FISH analysis.

PMID- 19405716
TI  - Forster resonance energy transfer-based total internal reflection fluorescence
      reader for apoptosis.
AB  - A fluorescence reader for the detection of Forster resonance energy transfer
      (FRET) on surfaces of living cells is described. The method is based on multiple
      total internal reflections (TIR) of an incident laser beam within a glass slide,
      such that individual samples on top of the glass slide are illuminated
      simultaneously by an evanescent electromagnetic field. Enhanced cyan fluorescent
      protein (ECFP) anchored to the inner leaflet of the plasma membrane is optically
      excited and transfers its excitation energy via the peptide linker Asp-Glu-Val
      Asp (DEVD) to an enhanced yellow fluorescent protein. Upon apoptosis, DEVD is
      cleaved, and energy transfer is disrupted, as proven by an increase of
      fluorescence intensity as well as of fluorescence lifetime of the donor ECFP. Due
      to selective excitation of membrane-associated fluorophores, intracellular
      fluorescence and background luminescence from the surrounding medium are
      eliminated. Therefore, this test system appears to be a sensitive device for the
      detection of apoptosis and more generally for drug screening or in vitro
      diagnosis on a nanometer scale.

PMID- 19405717
TI  - Fluorescent immunolabeling of cancer cells by quantum dots and antibody scFv
      fragment.
AB  - Semiconductor quantum dots (QDs) coupled with cancer-specific targeting ligands
      are new promising agents for fluorescent visualization of cancer cells. Human
      epidermal growth factor receptor 2/neu (HER2/neu), overexpressed on the surface
      of many cancer cells, is an important target for cancer diagnostics. Antibody
      scFv fragments as a targeting agent for direct delivery of fluorophores offer
      significant advantages over full-size antibodies due to their small size, lower
      cross-reactivity, and immunogenicity. We have used quantum dots linked to anti
      HER2/neu 4D5 scFv antibody to label HER2/neu-overexpressing live cells. Labeling
      of target cells was shown to have high brightness, photostability, and
      specificity. The results indicate that construction based on quantum dots and
      scFv antibody can be successfully used for cancer cell visualization.

PMID- 19405718
TI  - Study of gold nanoparticles and live cells interactions by using planar
      evanescent wave excitation.
AB  - We present a planar evanescent wave (PEW) technique combined with phase contrast
      optical microscopy to study the interactions between cells and gold nanoparticles
      (AuNPs). The PEW method employs a dual-fiber-line guide to couple light into a
      thin glass slide. It produces a uniform and long evanescent wave near the glass
      surface, as verified by the optical near-field measurement. High-contrast AuNP
      images are obtained by the PEW illumination. At the same time, cells are observed
      only by using the phase contrast microscopy. The nanoparticles and cell images
      indicated that unmodified AuNPs had no interactions with cells, possibly due to
      the negative surface charges on both cells and nanoparticles. The electrostatic
      concept was further verified by coating AuNPs with positively charged poly (L
      lysine). DNA aptamers for surface mucin glycoprotein were coated on AuNPs to
      demonstrate the application for single nanoparticle tracking.

PMID- 19405719
TI  - In vivo Raman flow cytometry for real-time detection of carbon nanotube kinetics
      in lymph, blood, and tissues.
AB  - Nanoparticles are intensively being explored as contrast agents for medical
      diagnostics and therapies using various optical methods. We present the first
      demonstration of the use of time-resolved Raman spectroscopy for in vivo real
      time detection of circulating carbon nanotubes (CNTs) or cancer cells labeled
      with CNTs in the lymph, blood, and tissues of live animals with fast spectral
      acquisition times of down to few milliseconds. After intravenously administering
      CNTs in the tail vein of the rat, this technique provides the ability to detect
      the circulation of CNTs in the blood microvessels of the intact rat ear. The
      capability of Raman spectroscopy is also demonstrated to monitor, identify, and
      image the CNTs during their transportation by lymphatics in the rat ear and
      mesentery. The strong and specific Raman scattering properties of CNTs make it
      possible to detect in vitro and in vivo single cancer cells (HeLa) tagged with
      CNTs. In vivo Raman flow cytometry opens a new avenue for multiparameter analysis
      of circulating nanoparticles with strong Raman scattering properties and their
      pharmokinetics in blood and lymph systems. Moreover, this technology has the
      potential for molecular detection and identification of circulating tumor cells,
      and infections labeled with CNTs.

PMID- 19405720
TI  - Nanophotothermolysis of multiple scattered cancer cells with carbon nanotubes
      guided by time-resolved infrared thermal imaging.
AB  - Nanophotothermolysis with long laser pulses for treatment of scattered cancer
      cells and their clusters is introduced with the main focus on real-time
      monitoring of temperature dynamics inside and around individual cancer cells
      labeled with carbon nanotubes. This technique utilizes advanced time- and
      spatially-resolved thermal radiometry imaging for the visualization of laser
      induced temperature distribution in multiple-point absorbing targets. The
      capability of this approach was demonstrated for monitoring of thermal effects
      under long laser exposure (from millisecond to seconds, wavelength 1,064 nm,
      maximum power 1 W) of cervical cancer HeLa cells labeled with carbon nanotubes in
      vitro. The applications are discussed with a focus on the nanophotothermolysis of
      small tumors, tumor margins, or micrometastases under the guidance of near-IR and
      microwave radiometry.

PMID- 19405721
TI  - Photoacoustic molecular imaging with antibody-functionalized single-walled carbon
      nanotubes for early diagnosis of tumor.
AB  - Single-walled carbon nanotubes (SWNT) in a poly(ethylene)ghycol solution are a
      biocompatible transporters with strong optical absorption in the near-infrared
      region, in which the biological tissue is almost transparent with very low
      absorbance. Here, antibody-functionalized SWNTs for tumor early detection with
      photoacoustic molecular imaging in vivo are reported. To lay the groundwork for
      this goal and insure system stability, images were collected in tissue simulating
      phantoms to determine appropriate detectable concentrations of SWNTs. Preliminary
      in vitro and in vivo results showed that a high contrast and a high efficient
      targeting of integrin alpha(v)beta(3) positive U87 human glioblastoma tumours in
      mice could be achieved. The nontoxicity of functionalized SWNTs has also been
      demonstrated in our experiment; this feature ensures that SWNTs can be used for
      clinical applications. This study suggests that photoacoustic molecular imaging
      with antibody-functionalized SWNTs has the potential to be an effective early
      tumor diagnosis method.

PMID- 19405723
TI  - Silicon nanoparticles produced by femtosecond laser ablation in water as novel
      contamination-free photosensitizers.
AB  - We report the synthesis of novel inorganic contamination-free photosensitizers
      based on colloidal silicon nanoparticles prepared by laser ablation in pure
      deionized water. We show that such nanoparticles are capable of generating
      singlet oxygen ((1)O(2)) under laser irradiation with a yield estimated at 10% of
      that of photofrin, which makes them a potential candidate for therapeutics,
      antiseptics, or disinfectants. We also discuss a model of (1)O(2) generation and
      the possibility for optimizing its release. Potential advantages of such novel
      inorganic photosensitizers include stable and nonphotobleaching (1)O(2) release,
      easy removal, and low dark toxicity.

PMID- 19405722
TI  - Cancer photothermal therapy in the near-infrared region by using single-walled
      carbon nanotubes.
AB  - Single-walled carbon nanotubes (SWNTs) have a high optical absorbance in the near
      infrared (NIR) region. In this special optical window, biological systems are
      known to be highly transparent. The optical properties of SWNTs provide an
      opportunity for selective photothermal therapy for cancer treatment.
      Specifically, CoMoCAT nanotubes with a uniform size (about 0.81 nm) and a narrow
      absorption peak at 980 nm are ideal candidates for such a novel approach. Here,
      CoMoCAT SWNTs are conjugated to folate, which can bind specifically to the
      surface of the folate receptor tumor markers. Folate-SWNT (FA-SWNT) targeted
      tumor cells were irradiated by a 980-nm laser. In our in vitro and in vivo
      experiments, FA-SWNT effectively enhanced the photothermal destruction on tumor
      cells and noticeably spared the photothermal destruction for nontargeted normal
      cells. Thus, SWNTs, combined with suitable tumor markers, can be used as novel
      nanomaterials for selective photothermal therapy for cancer treatment.

PMID- 19405724
TI  - Effect of size of TiO(2) nanoparticles applied onto glass slide and porcine skin
      on generation of free radicals under ultraviolet irradiation.
AB  - Titanium dioxide (TiO(2)) nanoparticles are extensively used today in sunscreens
      and coatings as protective compounds for human skin and material surfaces from UV
      radiation. In this paper, such particles are investigated by electron
      paramagnetic resonance spectroscopy as sources of free radicals under UV
      irradiation. The surface density of a placebo with embedded particles corresponds
      to the recommendations of dermatologists (2 mg cm(-2)). It is revealed that if
      applied onto glass, small particles 25 nm in diameter produce an increased amount
      of free radicals compared to the larger ones of 400 nm diam and the placebo
      itself. However, if applied onto porcine skin in vitro, there is no statistically
      distinct difference in the amount of radicals generated by the two kinds of
      particles on skin and by the skin itself. This proves that although particles as
      part of sunscreens produce free radicals, the effect is negligible in comparison
      to the production of radicals by skin in vitro.

PMID- 19405725
TI  - Delivery of optical contrast agents using Triton-X100, part 1: reversible
      permeabilization of live cells for intracellular labeling.
AB  - Effective delivery of optical contrast agents into live cells remains a
      significant challenge. We sought to determine whether Triton-X100, a detergent
      commonly used for membrane isolation and protein purification, could be used to
      effectively and reversibly permeabilize live cells for delivery of targeted
      optical contrast agents. Although Triton-X100 is widely recognized as a good cell
      permeabilization agent, no systematic study has evaluated the efficiency,
      reproducibility, and reversibility of Triton-X100-mediated permeabilization in
      live mammalian cells. We report a series of studies to characterize macromolecule
      delivery in cells following Triton-X100 treatment. Using this approach, we
      demonstrate that molecules ranging from 1 to 150 kDa in molecular weight can be
      reproducibly delivered into live cells by controlling the moles of Triton-X100
      relative to the number of cells to be treated. When Triton-X100 is administered
      at or near the minimum effective concentration, cell permeabilization is
      generally reversed within 24 h, and treated cells continue to proliferate and
      show metabolic activity during the restoration of membrane integrity. We conclude
      that Triton-X100 is a promising permeabilization agent for efficient and
      reproducible delivery of optical contrast agents into live mammalian cells.

PMID- 19405727
TI  - Determination of the cuticula thickness of human and porcine hairs and their
      potential influence on the penetration of nanoparticles into the hair follicles.
AB  - An efficient penetration and long-term storage of topically applied substances is
      important for drug delivery in medical treatment and cosmetics. It has recently
      become apparent that the hair follicles represent an efficient and long-term
      reservoir for topically applied substances. It was found that particles sized 300
      600 nm penetrate more efficiently into the hair follicles than smaller or larger
      particles. In the present paper, the hair surface structure of human and porcine
      hairs was analyzed by electron microscopy. It could be observed that the
      thickness of the cuticula corresponds to the optimal size of the nanoparticles
      for penetration into the hair follicles. Additionally, it could be demonstrated
      that the cuticula of human vellus and terminal hairs were of similar thickness
      (approx. 530 nm), while the thickness of the cuticula obtained from porcine ear
      bristles were slightly thinner (approx. 320 nm).

PMID- 19405726
TI  - Delivery of optical contrast agents using Triton-X100, part 2: enhanced mucosal
      permeation for the detection of cancer biomarkers.
AB  - Uniform delivery of optical contrast agents through mucosal tissue has proven a
      significant challenge. Topical permeation enhancers that have proven useful for
      skin demonstrate limited success in mucosal tissue. We sought to develop a
      topical permeation strategy capable of delivering tissue-impermeant molecular
      specific contrast agents through mucosal epithelium in a uniform, controlled
      manner. We demonstrate that Triton-X100 can be utilized to deliver targeted and
      untargeted optical contrast agents through freshly excised normal mucosal
      epithelium and epithelial cancer. Macromolecules up to 150 kDa in size were
      successfully delivered via transcellular and paracellular routes. The depth of
      Triton-mediated permeation was modulated by varying the treatment time and
      concentration. Uniform epithelial penetration to a depth of 500 mum was achieved
      in approximately 1.5 h for molecules of 40 kDa or less. Larger optical probes
      required longer treatment times. Coadministration of molecular-specific contrast
      agents with Triton-X100 treatment facilitated simultaneous labeling of biomarkers
      on the cell membrane, in the cytoplasm, and in the nucleus with high specificity.
      Together, these data suggest that Triton-X100 is a promising topical permeation
      enhancer for mucosal delivery of tissue-impermeant molecular-specific optical
      contrast agents.

PMID- 19405728
TI  - Qualitative detection of single submicron and nanoparticles in human skin by
      scanning transmission x-ray microscopy.
AB  - First results on single particle detection in human skin samples by x-ray
      microscopy are reported. 94+/-6 and 161+/-13 nm gold core particles with silica
      shells and 298+/-11 nm silica particles coated with a gold shell on
      ultramicrotome sections of human skin were determined. The particles were applied
      on fresh intact skin samples, which were sectioned prior to imaging. After
      screening the sections by conventional microscopy techniques, defined areas of
      interest were qualitatively investigated by scanning transmission x-ray
      microscopy at the Swiss Light Source. In studies on the percutaneous penetration
      of 161+/-13 nm particles on human skin samples, x-ray microscopy yielded high
      resolution images of single particles spreading on the superficial layer of the
      stratum corneum and on the epithelium in superficial parts of hair follicles. No
      deeper penetration was observed. The present work using x-ray microscopy provides
      the unique opportunity to study qualitative penetration processes and membrane
      particle interactions on the level of single particles. This goes beyond present
      approaches using optical microscopy. Further improvement of this approach will
      allow one to study particles with different physicochemical properties and
      surface modifications, including responses of the exposed tissue.

PMID- 19405729
TI  - Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer
      phototherapy.
AB  - We describe an application of plasmonic silica/gold nanoshells to produce a
      controllable laser hyperthermia in tissues with the aim of the enhancement of
      cancer photothermal therapy. Laser irradiation parameters are optimized on the
      basis of preliminary experimental studies using a test-tube phantom and
      laboratory rats. Temperature distributions on the animal skin surface at
      hypodermic and intramuscular injection of gold nanoparticle suspensions and
      affectations by the laser radiation are measured in vivo with a thermal imaging
      system. The results of temperature measurements are compared with tissue
      histology.

PMID- 19405730
TI  - Contrasting properties of gold nanoshells and titanium dioxide nanoparticles for
      optical coherence tomography imaging of skin: Monte Carlo simulations and in vivo
      study.
AB  - The effect of silica/gold nanoshells and titanium dioxide nanoparticles on the
      optical properties of skin is studied. By implementing in vivo measurements and
      Monte Carlo simulations, we analyze the efficiency of using these nanoparticles
      as contrasting agents for optical coherence tomography (OCT) imaging of skin. In
      vivo measurements are performed on pig skin, where nanoparticle suspension drops
      have been applied. The identification of skin layers is performed by comparison
      with corresponding histology images. Experimental results exhibit an increase in
      contrast of the obtained OCT images after a single nanoparticles application.
      Multiple applications do not lead to increase in the obtained contrast. To
      interpret the obtained experimental OCT images of skin and understand the
      mechanisms of contrasting, a set of Monte Carlo calculations is performed. The
      results of the simulations exhibit good qualitative agreement with the
      experimental images, and prove that the contrasting originates from the
      nanoparticles added, while the contrast of inclusion originates from the absence
      of nanoparticles within it and their presence in the surrounding area.

PMID- 19405731
TI  - Effects of Er:YAG laser irradiation and manipulation treatments on dentin
      components, part 1: Fourier transform-Raman study.
AB  - The effects of laser etching, decontamination, and storage treatments on dentin
      components were studied using Fourier transform (FT)-Raman spectroscopy. Thirty
      bovine incisors were prepared to expose the dentin surface and then divided in
      two main groups based upon the decontamination process and storage procedure:
      autoclaved (group A, n=15) or stored in thymol aqueous solution (group B, n=15).
      The surfaces of the dentin slices were schematically divided into four areas,
      with each one corresponding to a treatment subgroup. The specimens were either
      etched with phosphoric acid (control subgroup) or irradiated with erbium-doped
      yttrium-aluminum-garnet (Er:YAG) laser (subgroups: I-80 mJ, II-120 mJ, and III
      180 mJ, and total energy of 12 J). Samples were analyzed by FT-Raman
      spectroscopy; we collected three spectra for each area (before and after
      treatment). The integrated areas of five Raman peaks were calculated to yield
      average spectra. The areas of the peaks associated with phosphate content
      (P<0.001), type I collagen, and organic C-H bonds (P<0.05) were reduced
      significantly in group A (control). Analyses of samples irradiated with reduced
      laser energies did not show significant changes in the dentin components. These
      results suggest that thymol storage treatment is advised for in vitro study;
      furthermore, 12 J of Er:YAG laser energy does not affect dentin components.

PMID- 19405732
TI  - Effects of Er:YAG laser irradiation and manipulation treatments on dentin
      components, part 2: energy-dispersive X-ray fluorescence spectrometry study.
AB  - The effects of laser etching, decontamination, and storage treatments on dentin
      components were studied by energy-dispersive X-ray fluorescence spectrometry
      (EDXRF). Thirty bovine incisors were prepared to expose the dentin surface and
      then divided into two main groups based upon the decontamination process and
      storage procedure: autoclaved (group A, n=15) or stored in aqueous thymol
      solution (group B, n=15). The surfaces of the dentin slices were schematically
      divided into four areas, with each one corresponding to a treatment subgroup. The
      specimens were either etched with phosphoric acid (control subgroup) or
      irradiated with erbium-doped yttrium-aluminum-garnet (Er:YAG) laser (subgroups: I
      80 mJ, II-120 mJ, and III-180 mJ). Samples were analyzed by micro-EDXRF, yielding
      three spectra for each area (before and after treatment). Surface mappings
      covering an area of 80x60 points with steps of 20 mum were also performed on
      selected specimens. The amount of Ca and P in group A specimens decreased
      significantly (P<0.05) after the acid etching and the CaP ratio increased
      (P<0.001). Er:YAG laser-etching using lower laser energies did not produce
      significant changes in dentin components. The mapping data support the hypothesis
      that acid etching on dentin produced a more chemically homogeneous surface and
      thus a more favorable surface for the diffusion of adhesive monomers.

PMID- 19405733
TI  - Scanning illumination-acquisition system for noncontact optical tomography.
AB  - A new method for the detection of light traversing a diffuser/nondiffuser
      interface and its simultaneous determination for optical tomography is proposed,
      and the preliminary results are shown. The method is based on the use of a point
      detector and two uncoupled scanning systems-one for illumination and the other
      for registration-together with active modification of the optics guided by the
      surface topography to generate virtual detectors on the interface.

PMID- 19405734
TI  - In vivo fluorescence lifetime tomography.
AB  - Local molecular and physiological processes can be imaged in vivo through
      perturbations in the fluorescence lifetime (FLT) of optical imaging agents. In
      addition to providing functional information, FLT methods can quantify specific
      molecular events and multiplex diagnostic and prognostic information. We have
      developed a fluorescence lifetime diffuse optical tomography (DOT) system for in
      vivo preclinical imaging. Data is captured using a time-resolved intensified
      charge coupled device (ICCD) system to measure fluorescence excitation and
      emission in the time domain. Data is then converted to the frequency domain, and
      we simultaneously reconstruct images of yield and lifetime using an extension to
      the normalized Born approach. By using differential phase measurements, we
      demonstrate DOT imaging of short lifetimes (from 350 ps) with high precision (+/
      5 ps). Furthermore, this system retains the efficiency, speed, and flexibility of
      transmission geometry DOT. We demonstrate feasibility of FLT-DOT through a
      progressive series of experiments. Lifetime range and repeatability are first
      measured in phantoms. Imaging of subcutaneous implants then verifies the FLT-DOT
      approach in vivo in the presence of inhomogeneous optical properties. Use in a
      common research scenario is ultimately demonstrated by imaging accumulation of a
      targeted near-infrared (NIR) fluorescent-labeled peptide probe (cypate-RGD) in a
      mouse with a subcutaneous tumor.

PMID- 19405735
TI  - Rapid identification of anterior and posterior root of cauda equina nerves by
      near-infrared diffuse reflectance spectroscopy.
AB  - A new rapid chemometric method has been developed to identify the anterior and
      posterior roots of cauda equina nerves by near-infrared (NIR) diffuse reflectance
      spectroscopy. NIR spectra of nerves were measured using a Fourier transform NIR
      spectrometer equipped with a fiber-optic probe. The result revealed no observable
      difference in the spectra between the anterior and posterior root samples, but
      the two roots could be identified by cluster analysis based on the differences of
      their spectral features. The overall accuracy of the cluster analysis model was
      87.5%, and the accuracy for the actual anterior root and actual posterior root
      were 95% and 80%, respectively. The result suggested that NIR spectroscopy in
      combination with the chemometrics method (cluster analysis) could be used to
      classify the anterior and posterior roots of cauda equina nerves. The proposed
      method required only a few minutes, while classical methods commonly required at
      least one hour. It was demonstrated that the new method could provide a rapid,
      correct, nondestructive and low-cost potential means to quickly differentiate
      anterior and posterior roots in mixed cauda equina nerves, which would be helpful
      for surgeons to align nerve stumps correctly.

PMID- 19405736
TI  - Novel approach to assess the emissivity of the human skin.
AB  - To study the radiation emitted by the human skin, the emissivity of its surface
      must be known. We present a new approach to measure the emissivity of the human
      skin in vivo. Our method is based on the calculation of the difference of two
      infrared images: one acquired before projecting a CO(2) laser beam on the surface
      of the skin and the other after such projection. The difference image contains
      the radiation reflected by the skin, which is used to calculate the emissivity,
      making use of Kirchhoff's law and the Helmholtz reciprocity relation. With our
      method, noncontact measurements are achieved, and the determination of the skin
      temperature is not needed, which has been an inconvenience for other methods. We
      show that it is possible to make determinations of the emissivity at specific
      wavelengths. Last, our results confirm that the human skin obeys Lambert's law of
      diffuse reflection and that it behaves almost like a blackbody at a wavelength of
      10.6 microm.

PMID- 19405737
TI  - Laser optoacoustic imaging system for detection of breast cancer.
AB  - We designed, fabricated and tested the laser optoacoustic imaging system for
      breast cancer detection (LOIS-64), which fuses optical and acoustic imaging
      techniques in one modality by utilizing pulsed optical illumination and ultrawide
      band ultrasonic detection of resulting optoacoustic (OA) signals. The system was
      designed to image a single breast slice in craniocaudal or mediolateral
      projection with an arc-shaped array of 64 ultrawide-band acoustic transducers.
      The system resolution on breast phantoms was at least 0.5 mm. The single-channel
      sensitivity of 1.66 mVPa was estimated to be sufficient for single-pulse imaging
      of 6 to 11 mm tumors through the whole imaging slice of the breast. The
      implemented signal processing using the wavelet transform allowed significant
      reduction of the low-frequency (LF) acoustic noise, allowed localization of the
      optoacoustic signals from tumors, and enhanced the contrast and sharpened the
      boundaries of the optoacoustic images of the tumors. During the preliminary
      clinical studies on 27 patients, the LOIS-64 was able to visualize 18 out of 20
      malignant lesions suspected from mammography and ultrasound images and confirmed
      by the biopsy performed after the optoacoustic tomography (OAT) procedure.

PMID- 19405738
TI  - Confocal fluorescence microendoscopy of bronchial epithelium.
AB  - Confocal microendoscopy permits the acquisition of high-resolution real-time
      confocal images of bronchial mucosa via the instrument channel of an endoscope.
      We report here on the construction and validation of a confocal fluorescence
      microendoscope and its use to acquire images of bronchial epithelium in vivo. Our
      objective is to develop an imaging method that can distinguish preneoplastic
      lesions from normal epithelium to enable us to study the natural history of these
      lesions and the efficacy of chemopreventive agents without biopsy removal of the
      lesion that can introduce a spontaneous regression bias. The instrument employs a
      laser-scanning engine and bronchoscope-compatible confocal probe consisting of a
      fiber-optic image guide and a graded-index objective lens. We assessed the
      potential of topical application of physiological pH cresyl violet (CV) as a
      fluorescence contrast-enhancing agent for the visualization of tissue morphology.
      Images acquired ex vivo with the confocal microendoscope were first compared with
      a bench-top confocal fluorescence microscope and conventional histology. Confocal
      images from five sites topically stained with CV were then acquired in vivo from
      high-risk smokers and compared to hematoxylin and eosin stained sections of
      biopsies taken from the same site. Sufficient contrast in the confocal imagery
      was obtained to identify cells in the bronchial epithelium. However, further
      improvements in the miniature objective lens are required to provide sufficient
      axial resolution for accurate classification of preneoplastic lesions.

PMID- 19405739
TI  - In vitro imaging of remaining dentin and pulp chamber by optical coherence
      tomography: comparison between 850 and 1280 nm.
AB  - We report the application of optical coherence tomography (OCT) to generate
      images of the remaining dentin and pulp chamber of in vitro human teeth.
      Bidimensional images of remaining dentin and of the pulp chamber were obtained
      parallel to the long axis of the teeth, by two OCT systems operating around 1280
      and 850 nm, and compared to tomography images using the i-CAT(R) Cone Beam
      Volumetric Tomography system as the gold standard. The results demonstrated the
      efficacy of the OCT technique; furthermore, the wavelength close to 1280 nm
      presented greater penetration depth in the dentine than 850 nm, as expected from
      scattering and absorption coefficients. The OCT technique has great potential to
      be used on clinical practice, preventing accidental exposure of the pulp and
      promoting preventive restoration treatment.

PMID- 19405740
TI  - Quantitative diffuse reflectance and fluorescence spectroscopy: tool to monitor
      tumor physiology in vivo.
AB  - This study demonstrates the use of optical spectroscopy for monitoring tumor
      oxygenation and metabolism in response to hyperoxic gas breathing. Hemoglobin
      saturation and redox ratio were quantified for a set of 14 and 9 mice,
      respectively, measured at baseline and during carbogen breathing (95% O(2), 5%
      CO(2)). In particular, significant increases in hemoglobin saturation and
      fluorescence redox ratio were observed upon carbogen breathing. These data were
      compared with data obtained concurrently using an established invasive technique,
      the OxyLite partial oxygen pressure (pO(2)) system, which also showed a
      significant increase in pO(2). It was found that the direction of changes were
      generally the same between all of the methods, but that the OxyLite system was
      much more variable in general, suggesting that optical techniques may provide a
      better assessment of global tumor physiology. Optical spectroscopy measurements
      are demonstrated to provide a reliable, reproducible indication of changes in
      tumor physiology in response to physiologic manipulation.

PMID- 19405741
TI  - In vivo time-resolved spectroscopy of the human bronchial early cancer
      autofluorescence.
AB  - Time-resolved measurements of tissue autofluorescence (AF) excited at 405 nm were
      carried out with an optical-fiber-based spectrometer in the bronchi of 11
      patients. The objectives consisted of assessing the lifetime as a new
      tumor/normal (T/N) tissue contrast parameter and trying to explain the origin of
      the contrasts observed when using AF-based cancer detection imaging systems. No
      significant change in the AF lifetimes was found. AF bronchoscopy performed in
      parallel with an imaging device revealed both intensity and spectral contrasts.
      Our results suggest that the spectral contrast might be due to an enhanced blood
      concentration just below the epithelial layers of the lesion. The intensity
      contrast probably results from the thickening of the epithelium in the lesions.
      The absence of T/N lifetime contrast indicates that the quenching is not at the
      origin of the fluorescence intensity and spectral contrasts. These lifetimes (6.9
      ns, 2.0 ns, and 0.2 ns) were consistent for all the examined sites. The fact that
      these lifetimes are the same for different emission domains ranging between 430
      and 680 nm indicates that there is probably only one dominant fluorophore
      involved. The measured lifetimes suggest that this fluorophore is elastin.

PMID- 19405743
TI  - Noninvasive determination of cell nucleoplasmic viscosity by fluorescence
      correlation spectroscopy.
AB  - Noninvasive and reliable quantification of rheological characteristics in the
      nucleus is extremely useful for fundamental research and practical applications
      in medicine and biology. This study examines the use of fluorescence correlation
      spectroscopy (FCS) to noninvasively determine nucleoplasmic viscosity (eta(nu)),
      an important parameter of nucleoplasmic rheology. Our FCS analyses show that
      eta(nu) of lung adenocarcinoma (ASTC-a-1) and HeLa cells are 1.77+/-0.42 cP and
      1.40+/-0.27 cP, respectively, about three to four times larger than the water
      viscosity at 37 degrees C. eta(nu) was reduced by 31 to 36% upon hypotonic
      exposure and increased by 28 to 52% from 37 to 24 degrees C. In addition, we
      found that eta(nu) of HeLa cells reached the lowest value in the S phase and that
      there was no significant difference of eta(nu) between in the G1 and G2 phases.
      Last, nucleoplasmic viscosity was found to be larger than cytoplasmic viscosity
      in both HeLa and ASTC-a-1 cells. These results indicate that FCS can be used as a
      noninvasive tool to investigate the microenvironment of living cells. This is the
      first report on the measurement of eta(nu) in living cells synchronized in the
      G1, S, and G2 phases.

PMID- 19405742
TI  - Quantitation and mapping of tissue optical properties using modulated imaging.
AB  - We describe the development of a rapid, noncontact imaging method, modulated
      imaging (MI), for quantitative, wide-field characterization of optical absorption
      and scattering properties of turbid media. MI utilizes principles of frequency
      domain sampling and model-based analysis of the spatial modulation transfer
      function (s-MTF). We present and compare analytic diffusion and probabilistic
      Monte Carlo models of diffuse reflectance in the spatial frequency domain. Next,
      we perform MI measurements on tissue-simulating phantoms exhibiting a wide range
      of l values (0.5 mm to 3 mm) and (micro(s) (')micro(a)) ratios (8 to 500),
      reporting an overall accuracy of approximately 6% and 3% in absorption and
      reduced scattering parameters, respectively. Sampling of only two spatial
      frequencies, achieved with only three camera images, is found to be sufficient
      for accurate determination of the optical properties. We then perform MI
      measurements in an in vivo tissue system, demonstrating spatial mapping of the
      absorption and scattering optical contrast in a human forearm and dynamic
      measurements of a forearm during venous occlusion. Last, metrics of spatial
      resolution are assessed through both simulations and measurements of spatially
      heterogeneous phantoms.

PMID- 19405744
TI  - Spatiotemporal image correlation spectroscopy measurements of flow demonstrated
      in microfluidic channels.
AB  - Accurate blood flow measurements during surgery can improve an operation's chance
      of success. We developed near-infrared spatio-temporal image spectroscopy (NIR
      STICS), which has the potential to make blood flow measurements that are
      difficult to accomplish with existing methods. Specifically, we propose the
      technique and we show feasibility on phantom measurements. NIR-STICS has the
      potential of measuring the fluid velocity in small blood vessels (less than 1 mm
      in diameter) and of creating a map of blood flow rates over an area of
      approximately 1 cm(2). NIR-STICS employs near-infrared spectroscopy to probe
      inside blood vessel walls and spatiotemporal image correlation spectroscopy to
      directly-without the use of a model-extract fluid velocity from the fluctuations
      within an image. We present computer simulations and experiments on a phantom
      system that demonstrate the effectiveness of NIR-STICS.

PMID- 19405745
TI  - Ultrasound-modulated optical tomography in reflection mode with ring-shaped light
      illumination.
AB  - We have succeeded in implementing ring-shaped light illumination ultrasound
      modulated optical tomography (UOT) in reflection mode. The system used intense
      acoustic bursts and a charge-coupled device (CCD) camera-based speckle contrast
      detection method. In addition, the implementation allows placing the tissue
      sample below (not within) an acoustic coupling water tank and scanning the tissue
      without moving the sample. Thus, the UOT system is more clinically applicable
      than previous transmission-mode systems. Furthermore, we have successfully imaged
      an ex vivo methylene-blue-dyed sentinel lymph node (SLN) embedded at a depth of
      13 mm in chicken breast tissue. This UOT system offers several advantages:
      noninvasiveness, nonionizing radiation, portability, cost effectiveness, and the
      possibility of combination with ultrasound pulse-echo imaging and photoacoustic
      imaging. One potential application of the UOT system is mapping SLNs in axillary
      staging for breast cancer patients.

PMID- 19405746
TI  - Three-dimensional pointwise comparison of human retinal optical property at 845
      and 1060 nm using optical frequency domain imaging.
AB  - To compare the optical properties of the human retina, 3-D volumetric images of
      the same eye are acquired with two nearly identical optical coherence tomography
      (OCT) systems at center wavelengths of 845 and 1060 nm using optical frequency
      domain imaging (OFDI). To characterize the contrast of individual tissue layers
      in the retina at these two wavelengths, the 3-D volumetric data sets are
      carefully spatially matched. The relative scattering intensities from different
      layers such as the nerve fiber, photoreceptor, pigment epithelium, and choroid
      are measured and a quantitative comparison is presented. OCT retinal imaging at
      1060 nm is found to have a significantly better depth penetration but a reduced
      contrast between the retinal nerve fiber, the ganglion cell, and the inner
      plexiform layers compared to the OCT retinal imaging at 845 nm.

PMID- 19405747
TI  - Near-infrared autofluorescence imaging of cutaneous melanins and human skin in
      vivo.
AB  - In recent years, near-infrared (NIR) autofluorescence imaging has been explored
      as a novel technique for tissue evaluation and diagnosis. We present an NIR
      fluorescence imaging system optimized for the dermatologic clinical setting, with
      particular utility for the direct characterization of cutaneous melanins in vivo.
      A 785-nm diode laser is coupled into a ring light guide to uniformly illuminate
      the skin. A bandpass filter is used to purify the laser light for fluorescence
      excitation, while a long-pass filter is used to block the main laser wavelength
      but pass the spontaneous components for NIR reflectance imaging. A computer
      controlled filter holder is used to switch these two filters to select between
      reflectance and fluorescence imaging modes. Both the reflectance and fluorescence
      photons are collected by an NIR-sensitive charge-coupled device (CCD) camera to
      form the respective images. Preliminary results show that cutaneous melanin in
      pigmented skin disorders emits higher NIR autofluorescence than surrounding
      normal tissue. This confirmed our previous findings from NIR fluorescence
      spectroscopy study of cutaneous melanins and provides a new approach to directly
      image the distributions of cutaneous melanins in the skin. In-vivo NIR
      autofluorescence images may be useful for clinical evaluation and diagnosis of
      pigmented skin lesions, including melanoma.

PMID- 19405748
TI  - In vivo confocal imaging of epidermal cell migration and dermal changes post
      nonablative fractional resurfacing: study of the wound healing process with
      corroborated histopathologic evidence.
AB  - In vivo wound healing response post nonablative fractional laser treatment is
      evaluated. Seven healthy subjects receive treatments with a Fraxel re:store laser
      system on the forearm with pulse energies ranging from 10 to 70 mJ. The treatment
      sites are imaged at 1-h increments up to 40 h using confocal microscope z-stacks
      using 10-mum-depth spacing. At least five individual microscopic treatment zones
      are imaged per subject, time point, and treatment energy. Images are analyzed for
      tissue structure and morphology to classify each lesion as healed or not healed,
      depending on epidermal re-epithelialization at each time point and treatment
      energy. Probit analysis is used to statistically determine the ED(50) and ED(84)
      probabilities for a positive dose response (healed lesion) as a function of
      treatment energy. Confocal observations reveal epidermal keratinocyte migration
      patterns confirmed with histological analysis using hematoxylin and eosin (HE)
      and lactate dehydrogenase (LDH) staining at 10 mJ at 0, 7, 16, and 24-h post
      treatment. Results indicate that more time is required to conclude re
      epithelialization with larger lesion sizes (all less than 500 mum) corresponding
      to higher treatment energies. For the entire pulse energy range tested, epidermal
      re-epithelialization concludes between 10 to 22-h post-treatment for ED(50) and
      13 to 28 h for ED(84).

PMID- 19405749
TI  - Optical clearing of the skin for near-infrared fluorescence image-guided surgery.
AB  - Near-infrared (NIR) light penetrates relatively deep into skin, but its
      usefulness for biomedical imaging is constrained by high scattering of living
      tissue. Previous studies have suggested that treatment with hyperosmotic
      "clearing" agents might change the optical properties of tissue, resulting in
      improved photon transport and reduced scatter. Since this would have a profound
      impact on image-guided surgery, we seek to quantify the magnitude of the optical
      clearing effect in living subjects. A custom NIR imaging system is used to
      perform sentinel lymph node mapping and superficial perforator angiography in
      vivo on 35-kg pigs in the presence or absence of glycerol or polypropylene
      glycol:polyethylene glycol (PPG:PEG) pretreatment of skin. Ex-vivo, NIR
      fluorescent standards are placed at a fixed distance beneath sections of excised
      porcine skin, either preserved in saline or stored dry, then treated or not
      treated with glycerol. Fluorescence intensity through the skin is quantified and
      analyzed statistically. Surprisingly, the expected increase in intensity is not
      measurable either in vivo or ex vivo, unless the skin is previously dried.
      Histological evaluation shows a morphological difference only in stratum corneum,
      with this difference being negligible in living tissue. In conclusion, topically
      applied hyperosmotic agents are ineffective for image-guided surgery of living
      subjects.

PMID- 19405751
TI  - Objective refraction from aberrometry: theory.
AB  - A theoretical framework to formulate and solve the problem of obtaining the
      objective refraction of an eye from aberrometric data is presented. Matrix
      formalism was applied to represent lens power and beam vergences in standard
      clinical, sphere+cylinder (S+C) refraction, and to describe the vergence error of
      a general aberrated skew ray. The vergence error matrix of each ray passing
      through the pupil is obtained, and the global refractive error is obtained by
      simple pupil average. The 2 x 2 vergence error matrix of a skew ray can be
      decomposed into the sum of two even-symmetric and odd-symmetric contributions.
      The even symmetric part corresponds to classic S+C refractive errors. The odd
      component can not be corrected with standard lenses. All odd components have zero
      mean over pupil, and do not contribute to the global refractive error, which is
      completely determined by S+C components. The contributions of wavefront Zernike
      modes to the global vergence error were obtained: The contributions of odd orders
      are zero, but all even HOA, but spherical aberration, contribute to refractive
      error. The matrix formulation of power and vergence errors provided a direct,
      simple way to use aberrometers as objective refractometers.

PMID- 19405752
TI  - Calibration beads containing luminescent lanthanide ion complexes.
AB  - The reliability of lanthanide luminescence measurements, by both flow cytometry
      and digital microscopy, would be enhanced by the availability of narrowband
      emitting, UV excited lanthanide calibration beads. 0.5-, 3-, and 5-microm beads
      containing a luminescent europium-complex are manufactured. The luminescence
      distribution of the 5-microm beads is measured with a time-delayed light-scatter
      gated luminescence flow cytometer to have a 7.0% coefficient of variation (CV)
      The spacial distribution of the europium-complex in individual beads is
      determined to be homogeneous by confocal microscopy. Emission peaks are found at
      592, 616 (width 9.9 nm), and 685 nm with a PARISS spectrophotometer. The kinetics
      of the luminescence bleaching caused by UV irradiation of the 0.5- and 5-microm
      beads measured under LED excitation with a fluorescence microscope indicate that
      bleaching does not interfere with their imaging. The luminescence lifetimes in
      water and air were 340 and 460 micros, respectively. Thus, these 5-microm beads
      can be used for spectral calibration of microscopes equipped with a spectrograph,
      as test particles for time-delayed luminescence flow cytometers, and possibly as
      labels for macromolecules and cells.

PMID- 19405753
TI  - Time-gated flow cytometry: an ultra-high selectivity method to recover ultra-rare
      event mu-targets in high-background biosamples.
AB  - A fundamental problem for rare-event cell analysis is auto-fluorescence from
      nontarget particles and cells. Time-gated flow cytometry is based on the temporal
      domain discrimination of long-lifetime (>1 micros) luminescence-stained cells and
      can render invisible all nontarget cell and particles. We aim to further evaluate
      the technique, focusing on detection of ultra-rare-event 5-microm calibration
      beads in environmental water dirt samples. Europium-labeled 5-microm calibration
      beads with improved luminescence homogeneity and reduced aggregation were
      evaluated using the prototype UV LED excited time-gated luminescence (TGL) flow
      cytometer (FCM). A BD FACSAria flow cytometer was used to sort accurately a very
      low number of beads (<100 events), which were then spiked into concentrated
      samples of environmental water. The use of europium-labeled beads permitted the
      demonstration of specific detection rates of 100%+/-30% and 91%+/-3% with 10 and
      100 target beads, respectively, that were mixed with over one million nontarget
      autofluorescent background particles. Under the same conditions, a conventional
      FCM was unable to recover rare-event fluorescein isothiocyanate (FITC)
      calibration beads. Preliminary results on Giardia detection are also reported. We
      have demonstrated the scientific value of lanthanide-complex biolabels in flow
      cytometry. This approach may augment the current method that uses
      multifluorescence-channel flow cytometry gating.

PMID- 19405755
TI  - Improved depth resolution in near-infrared diffuse reflectance spectroscopy using
      obliquely oriented fibers.
AB  - We demonstrate a significant improvement of depth selectivity when using
      obliquely oriented fibers for near-infrared (NIR) diffuse reflectance
      spectroscopy. This is confirmed by diffuse reflectance measurements of a two
      layer tissue-mimicking phantom across the spectral range from 1,000 to 1,940 nm.
      The experimental proof is supported by Monte Carlo simulations. The results
      reveal up to fourfold reduction in the mean optical penetration depth, twofold
      reduction in its variation, and a decrease in the number of scattering events
      when a single fiber is oriented at an angle of 60 deg. The effect of reducing the
      mean optical penetration depth is enhanced by orienting both fibers inwardly.
      Using outwardly oriented fibers enables more selective probing of deeper layers,
      while reducing the contribution from surface layers. We further demonstrate that
      the effect of an inward oblique arrangement can be approximated to a decrease in
      fiber-to-fiber separation in the case of a perpendicular fiber arrangement. This
      approximation is valid in the weak- or absorption-free regime. Our results assert
      the advantages of using obliquely oriented fibers when attempting to specifically
      address superficial tissue layers, for example, for skin cancer detection, or in
      noninvasive glucose monitoring. Such flexibility could be further advantageous in
      a range of minimally invasive applications, including catheter-based
      interventions.

PMID- 19405750
TI  - Differentiation of benign and malignant breast tumors by in-vivo three
      dimensional parallel-plate diffuse optical tomography.
AB  - We have developed a novel parallel-plate diffuse optical tomography (DOT) system
      for three-dimensional in vivo imaging of human breast tumor based on large
      optical data sets. Images of oxy-, deoxy-, and total hemoglobin concentration as
      well as blood oxygen saturation and tissue scattering were reconstructed. Tumor
      margins were derived using the optical data with guidance from radiology reports
      and magnetic resonance imaging. Tumor-to-normal ratios of these endogenous
      physiological parameters and an optical index were computed for 51 biopsy-proven
      lesions from 47 subjects. Malignant cancers (N=41) showed statistically
      significant higher total hemoglobin, oxy-hemoglobin concentration, and scattering
      compared to normal tissue. Furthermore, malignant lesions exhibited a twofold
      average increase in optical index. The influence of core biopsy on DOT results
      was also explored; the difference between the malignant group measured before
      core biopsy and the group measured more than 1 week after core biopsy was not
      significant. Benign tumors (N=10) did not exhibit statistical significance in the
      tumor-to-normal ratios of any parameter. Optical index and tumor-to-normal ratios
      of total hemoglobin, oxy-hemoglobin concentration, and scattering exhibited high
      area under the receiver operating characteristic curve values from 0.90 to 0.99,
      suggesting good discriminatory power. The data demonstrate that benign and
      malignant lesions can be distinguished by quantitative three-dimensional DOT.

PMID- 19405754
TI  - Uniform-intensity, visible light source for in situ imaging.
AB  - A flexible, low-cost, high-brightness light source for biological and biomedical
      imaging is presented. The illuminating device consists of a custom-size square
      plastic pouch 10 to 20 mm on a side and 1 to 3 mm thick that can be inserted
      fully or partially into both in situ or in vitro specimens to be imaged. The
      pouch contains a silicone-based gel medium embedded with silica particles that
      scatters light and provides a reasonably uniform, planar light source. Light is
      delivered to the pouch using a multimode optical fiber and a high-intensity
      tungsten lamp. Pouch size and geometry can be readily altered as needed for a
      particular application. Benefits of the device include reasonably uniform light
      intensity, low temperature rise (<2 degrees C), a nearly white light spectrum,
      and a thin (<2 mm thick) flexible form factor. The design, fabrication, and
      preliminary results from the device are presented using hamster cheek pouch
      tissue, with comparisons to standard intravital microscopy, along with
      suggestions for further improvement and potential uses.

PMID- 19405756
TI  - Comparison of human and porcine skin for characterization of sunscreens.
AB  - The universal sun protection factor (USPF) characterizing sunscreen efficacy
      based on spectroscopically determined data, which were obtained using the tape
      stripping procedure. The USPF takes into account the complete ultraviolet (UV)
      spectral range in contrast to the classical sun protection factor (SPF). Until
      now, the USPF determination has been evaluated only in human skin. However,
      investigating new filters not yet licensed excludes in vivo investigation on
      human skin but requires the utilization of a suitable skin model. The penetration
      behavior and the protection efficacy of 10 commercial sunscreens characterized by
      USPF were investigated, comparing human and porcine skin. The penetration
      behavior found for typical UV filter substances is nearly identical for both skin
      types. The comparison of the USPF obtained for human and porcine skin results in
      a linear relation between both USPF values with a correlation factor R(2)=0.98.
      The results demonstrate the possibility for the use of porcine skin to determine
      the protection efficacy of sunscreens.

PMID- 19405758
TI  - Application of hyperosmotic agent to determine gastric cancer with optical
      coherence tomography ex vivo in mice.
AB  - Noninvasive tumor imaging could lead to the early detection and timely treatment
      of cancer. Optical coherence tomography (OCT) has been reported as an ideal
      diagnostic tool for distinguishing tumor tissues from normal tissues based on
      structural imaging. In this study, the capability of OCT for functional imaging
      of normal and tumor tissues based on time- and depth-resolved quantification of
      the permeability of biomolecules through these tissues is investigated. The
      orthotopic graft model of gastric cancer in nude mice is used, normal and tumor
      tissues from the gastric wall are imaged, and a diffusion of 20% aqueous solution
      of glucose in normal stomach tissues and gastric tumor tissues is monitored and
      quantified as a function of time and tissue depth by an OCT system. Our results
      show that the permeability coefficient is (0.94+/-0.04)x10(-5) cms in stomach
      tissues and (5.32+/-0.17)x10(-5) cms in tumor tissues, respectively, and that
      tumor tissues have a higher permeability coefficient compared to normal tissues
      in optical coherence tomographic images. From the results, it is found that the
      accurate and sensitive assessment of the permeability coefficients of normal and
      tumor tissues offers an effective OCT image method for detection of tumor tissues
      and clinical diagnosis.

PMID- 19405759
TI  - Fully automated deconvolution method for on-line analysis of time-resolved
      fluorescence spectroscopy data based on an iterative Laguerre expansion
      technique.
AB  - Time-resolved fluorescence spectroscopy (TRFS) is a powerful analytical tool for
      quantifying the biochemical composition of organic and inorganic materials. The
      potential of TRFS for tissue diagnosis has been recently demonstrated. To
      facilitate the translation of TRFS to the clinical arena, algorithms for online
      TRFS data analysis are essential. A fast model-free TRFS deconvolution algorithm
      based on the Laguerre expansion method has previously been introduced. One
      limitation of this method, however, is the need to heuristically select two
      parameters that are crucial for the accurate estimation of the fluorescence
      decay: the Laguerre parameter alpha and the expansion order. Here, a new
      implementation of the Laguerre deconvolution method is introduced, in which a
      nonlinear least-square optimization of the Laguerre parameter alpha is performed,
      and the optimal expansion order is selected based on a minimum description length
      criterion (MDL). In addition, estimation of the zero-time delay between the
      recorded instrument response and fluorescence decay is also performed based on
      normalized mean square error criterion (NMSE). The method is validated on
      experimental data from fluorescence lifetime standards, endogenous tissue
      fluorophores, and human tissue. The proposed automated Laguerre deconvolution
      method will facilitate online applications of TRFS, such as real-time clinical
      tissue diagnosis.

PMID- 19405757
TI  - Tangential resolution improvement in thermoacoustic and photoacoustic tomography
      using a negative acoustic lens.
AB  - We developed a novel concept of using a negative acoustic lens to increase the
      acceptance angle of an unfocused large-area ultrasonic transducer (detector),
      leading to more than twofold improvement of the tangential resolution in both
      thermoacoustic and photoacoustic tomography. In both thermoacoustic and
      photoacoustic tomography, for a given transducer bandwidth, the aperture size of
      the detector affects the tangential resolution greatly when the object of
      interest is near the detector surface. We were able to overcome such tangential
      resolution deterioration by attaching an acoustic concave lens, made of acrylic
      in front of the flat detector surface. We then quantified the tangential
      resolution improvement using phantom images. We also showed that the use of the
      negative lens preserves the shape of an object after the image is reconstructed.

PMID- 19405760
TI  - Re-evaluation of model-based light-scattering spectroscopy for tissue
      spectroscopy.
AB  - Model-based light scattering spectroscopy (LSS) seemed a promising technique for
      in-vivo diagnosis of dysplasia in multiple organs. In the studies, the residual
      spectrum, the difference between the observed and modeled diffuse reflectance
      spectra, was attributed to single elastic light scattering from epithelial
      nuclei, and diagnostic information due to nuclear changes was extracted from it.
      We show that this picture is incorrect. The actual single scattering signal
      arising from epithelial nuclei is much smaller than the previously computed
      residual spectrum, and does not have the wavelength dependence characteristic of
      Mie scattering. Rather, the residual spectrum largely arises from assuming a
      uniform hemoglobin distribution. In fact, hemoglobin is packaged in blood
      vessels, which alters the reflectance. When we include vessel packaging, which
      accounts for an inhomogeneous hemoglobin distribution, in the diffuse reflectance
      model, the reflectance is modeled more accurately, greatly reducing the amplitude
      of the residual spectrum. These findings are verified via numerical estimates
      based on light propagation and Mie theory, tissue phantom experiments, and
      analysis of published data measured from Barrett's esophagus. In future studies,
      vessel packaging should be included in the model of diffuse reflectance and use
      of model-based LSS should be discontinued.

PMID- 19405761
TI  - Extended-working-distance multiphoton micromanipulation microscope for deep
      penetration imaging in live mice and tissue.
AB  - We constructed a multiphoton (2-P) microscope with space to mount and operate
      microphysiology hardware, and still acquire high quality 2-P images of tumor
      cells deep within tissues of live mice. We reconfigured for nondescanned 2-P
      imaging, a dedicated electrophysiology microscope, the Nikon FN1. This microscope
      is compact, with retractable objectives, allowing more stage space. The
      instrument is fitted with long-working-distance objectives (2.5- to 3.5-mm WD)
      with a narrow bore, high NA, and efficient UV and IR light transmission. The
      system is driven by a powerful 3.5-W peak power pulsed Ti-sapphire laser with a
      broad tuning range. This 2-P system images a fluorescent standard to a depth of
      750 to 800 microm, acquires images of murine pancreatic tumors in vivo, and also
      images fluorescently labeled T-cells inside live, externalized mouse lymph nodes.
      Effective imaging depths range between 100 and 500 microm. This compares
      favorably with the 100- to 300 microm micron depth attained by many 2-P systems,
      especially descanned 2-P instruments, and 40-microm-deep imaging with confocal
      microscopes. The greater depth penetration is attributable to the use of high-NA
      long-working-distance water-dipping lenses incorporated into a nondescanned
      instrument with carefully configured laser beam introduction and image
      acquisition optics. Thus the new system not only has improved imaging
      capabilities, but allows micromanipulation and maintenance of tissues and organs.

PMID- 19405763
TI  - Visualizing laser-skin interaction in vivo by multiphoton microscopy.
AB  - Recently, multiphoton microscopy has gained much popularity as a noninvasive
      imaging modality in biomedical research. We evaluate the potential of multiphoton
      microscopy for monitoring laser-skin reaction in vivo. Nude mouse skin is
      irradiated with an erbium:YAG laser at various fluences and immediately imaged by
      a multiphoton microscope. The alterations of cutaneous nonlinear optical
      properties including multiphoton autofluorescence and second-harmonic generation
      associated with laser irradiation are evaluated morphologically and
      quantitatively. Our results show that an erbium:YAG laser at a low fluence can
      selectively disrupt the stratum corneum, and this alteration may account for the
      penetration enhancing effect of laser-assisted transcutaneous drug delivery. At a
      higher fluence, the zone of tissue ablation as well as the disruption of the
      surrounding stratum corneum, keratinocytes, and dermal extracellular matrix can
      be better characterized by multiphoton microscopy as compared with conventional
      histology. Furthermore, the degree of collagen damage in the residual thermal
      zone can be quantified by second-harmonic generation signals, which have
      significant difference between control skin, skin irradiated with a 1.5-, 8-, and
      16-J/cm2 erbium:YAG laser (P<0.05). We show that multiphoton microscopy can be a
      useful noninvasive imaging modality for monitoring laser-skin reaction in vivo.

PMID- 19405762
TI  - Imaging cortical absorption, scattering, and hemodynamic response during ischemic
      stroke using spatially modulated near-infrared illumination.
AB  - We describe a technique that uses spatially modulated near-infrared (NIR)
      illumination to detect and map changes in both optical properties (absorption and
      reduced scattering parameters) and tissue composition (oxy- and deoxyhemoglobin,
      total hemoglobin, and oxygen saturation) during acute ischemic injury in the rat
      barrel cortex. Cerebral ischemia is induced using an open vascular occlusion
      technique of the middle cerebral artery (MCA). Diffuse reflected NIR light (680
      to 980 nm) from the left parietal somatosensory cortex is detected by a CCD
      camera before and after MCA occlusion. Monte Carlo simulations are used to
      analyze the spatial frequency dependence of the reflected light to predict
      spatiotemporal changes in the distribution of tissue absorption and scattering
      properties in the brain. Experimental results from seven rats show a 17+/-4.7%
      increase in tissue concentration of deoxyhemoglobin and a 45+/-3.1, 23+/-5.4, and
      21+/-2.2% decrease in oxyhemoglobin, total hemoglobin concentration and cerebral
      tissue oxygen saturation levels, respectively, 45 min following induction of
      cerebral ischemia. An ischemic index (I(isch)=ctHHbctO(2)Hb) reveals an average
      of more then twofold contrast after MCAo. The wavelength-dependence of the
      reduced scattering (i.e., scatter power) decreased by 35+/-10.3% after MCA
      occlusion. Compared to conventional CCD-based intrinsic signal optical imaging
      (ISOI), the use of structured illumination and model-based analysis allows for
      generation of separate maps of light absorption and scattering properties as well
      as tissue hemoglobin concentration. This potentially provides a powerful approach
      for quantitative monitoring and imaging of neurophysiology and metabolism with
      high spatiotemporal resolution.

PMID- 19405764
TI  - Optical properties of the medulla and the cortex of human scalp hair.
AB  - An increasing number of applications, including non- or minimally invasive
      diagnostics and treatment as well as various cosmetic procedures, has resulted in
      a need to determine the optical properties of hair and its structures. We report
      on the measurement of the total attenuation coefficient of the cortex and the
      medulla of blond, gray, and Asian black human scalp hair at a 633-nm wavelength.
      Our results show that for blond and gray hair the total attenuation coefficient
      of the medulla is more than 200 times higher compared to that of the cortex. This
      difference is only 1.5 times for Asian black hair. Furthermore, we present the
      total attenuation coefficient of the cortex of blond, gray, light brown, and
      Asian black hair measured at wavelengths of 409, 532, 633, 800, and 1064 nm. The
      total attenuation coefficient consistently decreases with an increase in
      wavelength, as well as with a decrease in hair pigmentation. Additionally, we
      demonstrate the dependence of the total attenuation coefficient of the cortex and
      the medulla of Asian black hair on the polarization of incident light. A similar
      dependence is observed for the cortex of blond and gray hair but not for the
      medulla of these hair types.

PMID- 19405765
TI  - Ellipsometric surface plasmon resonance.
AB  - We develop a new multifunctional optical biochip system that integrates an
      ellipsometer with a surface plasmon resonance (SPR) feature. This newly developed
      biochip biosensor, which we call ESPR for an ellipsometric SPR, provides us with
      a system to retrieve detailed information such as the optical properties of
      immobilized biomolecular monolayers, surface concentration variations of
      biomedical reactions, and kinetic affinity between biomolecules required for
      further biotech analysis. Our ESPR can also serve as both a research and
      development tool and a manufacturing tool for various biomedical applications.

PMID- 19405766
TI  - Time-resolved observation of surface-enhanced Raman scattering from gold
      nanoparticles during transport through a living cell.
AB  - We perform time-resolved observation of living cells with gold nanoparticles
      using surface-enhanced Raman scattering (SERS). The position and SERS spectra of
      50-nm gold nanoparticles are simultaneously observed by slit-scanning Raman
      microscopy with high spatial and temporal resolution. From the SERS observation,
      we confirm the attachment of the particles on the cell surface and the entry into
      the cell with the subsequent generation of SERS signals from nearby molecules. We
      also confirm that the strong dependence of SERS spectra on the position of the
      particle during the transportation of the particle through the cell. The obtained
      SERS spectra and its temporal fluctuation indicate that the molecular signals
      observable by this technique are given only from within a limited volume in close
      proximity to the nanoparticles. This confirms the high spatial selectivity and
      resolution of SERS imaging for observation of biomolecules involved in cellular
      events in situ.

PMID- 19405767
TI  - Raman spectroscopic analysis of the increase of the carotenoid antioxidant
      concentration in human skin after a 1-week diet with ecological eggs.
AB  - Skin aging is mainly caused by the destructive action of free radicals, produced
      by the UV light of the sun. The human skin has developed a protection system
      against these highly reactive molecules in the form of the antioxidative
      potential. Carotenoids are one of the main components of the antioxidants of the
      human skin. From former studies, it is known that skin aging is reduced in
      individuals with high levels of carotenoids. Because most of the antioxidants
      cannot be produced by the human organism, they must be up taken by nutrition.
      Using noninvasive Raman spectroscopic measurements it is demonstrated that not
      only fruits and vegetables but also eggs contain high concentrations of
      antioxidants including carotenoids, which are even doubled in the case of
      ecological eggs. After a 1-week diet with ecological eggs performed by six
      volunteers, it is found that the concentration of the carotenoids in the skin of
      the volunteers increased by approx. 20%. Our study does not intend to recommend
      exorbitant egg consumption, as eggs also contain harmful cholesterol. But in the
      case of egg consumption, ecological eggs from hens kept on pasture should be
      preferred to also receive a benefit for the skin.

PMID- 19405769
TI  - Characterizing liquid turbid media by frequency-domain photon-migration
      spectroscopy.
AB  - We present a wavelength-tunable frequency-domain instrument for the
      characterization of liquid turbid media. The instrument employs a tunable
      titanium-sapphire laser modulated by an acousto-optic modulator. The absorption
      and reduced scattering coefficient of Intralipid(R) 20%, diluted to
      concentrations of 0.94 to 4.00%, are measured over the wavelength range 710 to
      850 nm at 10-nm intervals. The standard measurement errors for the absorption and
      reduced scattering coefficients are 1 and 2.5%, respectively. Extrapolation to 0%
      Intralipid(R) concentration gives an absorption coefficient that closely follows
      that of water, overestimating the absorption of pure water by less than 10%. The
      reduced scattering coefficient is compared at 750 nm with published results and
      is found consistent within the experimental error. We compare the reduced
      scattering coefficient to an estimate based on Mie theory and find the reduced
      scattering coefficient underestimated the Mie theory result by about 9%.

PMID- 19405768
TI  - Femtosecond laser ablation of the stapes.
AB  - A femtosecond laser, normally used for LASIK eye surgery, is used to perforate
      cadaveric human stapes. The thermal side effects of bone ablation are measured
      with a thermocouple in an inner ear model and are found to be within acceptable
      limits for inner ear surgery. Stress and acoustic events, recorded with
      piezoelectric film and a microphone, respectively, are found to be negligible.
      Optical microscopy, scanning electron microscopy, and optical coherence
      tomography are used to confirm the precision of the ablation craters and lack of
      damage to the surrounding tissue. Ablation is compared to that from an Er:YAG
      laser, the current laser of choice for stapedotomy, and is found to be superior.
      Ultra-short-pulsed lasers offer a precise and efficient ablation of the stapes,
      with minimal thermal and negligible mechanical and acoustic damage. They are,
      therefore, ideal for stapedotomy operations.

PMID- 19405770
TI  - Bipolar cellular morphology of malignant melanoma in unstained human melanoma
      skin tissue.
AB  - Microstructures of unstained human melanoma skin tissues have been examined by
      multimodal nonlinear optical microscopy. The polarized shape of the individual
      melanoma cell can be readily recognized-a phenotype that has been identified in
      laboratory cultures as characteristic of proliferating melanocytes but has not
      been demonstrated in clinical instances. The results thus provide snapshots of
      invading melanoma cells in their native environment and suggest a practical means
      of connecting in vitro laboratory studies to in vivo processes.

PMID- 19405771
TI  - Ultrasound-modulated fluorescence based on a fluorophore-quencher-labeled
      microbubble system.
AB  - Ultrasound-modulated fluorescence from a fluorophore-quencher-labeled microbubble
      system driven by a single ultrasound pulse was theoretically quantified by
      solving a modified Herring equation (for bubble oscillation), a two-energy-level
      rate equation (for fluorophore excitation), and a diffusion equation (for light
      propagation in tissue). The efficiency of quenching caused by fluorescence
      resonance energy transfer (FRET) between the fluorophore and the quencher was
      modulated when the microbubble oscillates in size driven by the ultrasound pulse.
      Both intensity- and lifetime-based imaging methods are discussed in three
      different illumination modes of the excitation light: continuous wave (DC),
      frequency domain (FD), and time domain (TD). Results show that microbubble
      expansion opens a time period during which the quenching efficiency is
      dramatically reduced so that the emitted fluorescence strength and fluorophore
      lifetime are significantly increased. The modulation efficiency may even reach
      100%. In addition, an important finding in this study is that in TD illumination
      mode, the modulated fluorescence photons may be temporally separated from the
      unmodulated photons, which makes the modulation efficiency limited only by
      thermal noise of the measurement system.

PMID- 19405772
TI  - Near-infrared narrow-band imaging of gold/silica nanoshells in tumors.
AB  - Gold nanoshells (GNS) are a new class of nanoparticles that can be optically
      tuned to scatter or absorb light from the near-ultraviolet to near-infrared (NIR)
      region by varying the core (dielectric silica)/shell (gold) ratio. In addition to
      spectral tunability, GNS are inert and bioconjugatable, making them potential
      labels for in vivo imaging and therapy of tumors. We report the use of GNS as
      exogenous contrast agents for enhanced visualization of tumors using narrow-band
      imaging (NBI). NBI takes advantage of the strong NIR absorption of GNS to
      distinguish between blood and nanoshells in the tumor by imaging in narrow
      wavelength bands in the visible and NIR, respectively. Using tissue-simulating
      phantoms, we determined the optimum wavelengths to enhance contrast between blood
      and GNS. We then used the optimum wavelengths for ex vivo imaging of tumors
      extracted from human colon cancer xenograft bearing mice injected with GNS.
      Systemically delivered GNS accumulated passively in tumor xenografts by the
      enhanced permeability and retention (EPR) effect. Ex vivo NBI of tumor xenografts
      demonstrated heterogeneous distribution of GNS with a clear distinction from the
      tumor vasculature. The results of this study demonstrate the feasibility of using
      GNS as contrast agents to visualize tumors using NBI.

PMID- 19405773
TI  - Registration of planar bioluminescence to magnetic resonance and x-ray computed
      tomography images as a platform for the development of bioluminescence tomography
      reconstruction algorithms.
AB  - The procedures we propose make possible the mapping of two-dimensional (2-D)
      bioluminescence image (BLI) data onto a skin surface derived from a three
      dimensional (3-D) anatomical modality [magnetic resonance (MR) or computed
      tomography (CT)] dataset. This mapping allows anatomical information to be
      incorporated into bioluminescence tomography (BLT) reconstruction procedures and,
      when applied using sources visible to both optical and anatomical modalities, can
      be used to evaluate the accuracy of those reconstructions. Our procedures, based
      on immobilization of the animal and a priori determined fixed projective
      transforms, should be more robust and accurate than previously described efforts,
      which rely on a poorly constrained retrospectively determined warping of the 3-D
      anatomical information. Experiments conducted to measure the accuracy of the
      proposed registration procedure found it to have a mean error of 0.36+/-0.23 mm.
      Additional experiments highlight some of the confounds that are often overlooked
      in the BLT reconstruction process, and for two of these confounds, simple
      corrections are proposed.

PMID- 19405774
TI  - Three-wavelength technique for the measurement of oxygen saturation in arterial
      blood and in venous blood.
AB  - Pulse oximetry is an optical technique for the assessment of oxygen saturation in
      arterial blood and is based on the different light absorption spectra for
      oxygenated and deoxygenated hemoglobin and on two-wavelength
      photoplethysmographic (PPG) measurement of arterial blood volume increase during
      systole. The technique requires experimental calibration for the determination of
      the relationship between PPG-derived parameters and arterial oxygen saturation,
      and this calibration is a source of error in the method. We suggest a three
      wavelength PPG technique for the measurement of arterial oxygen saturation that
      has no need for calibration if the three wavelengths are properly selected in the
      near-infrared region. The suggested technique can also be implemented for the
      assessment of venous oxygen saturation by measuring the decrease in transmission
      of light through a tissue after increasing its blood volume by venous occlusion.
      The oxygen saturation in venous blood is a parameter that is related to oxygen
      consumption in tissue and to tissue blood flow. The three-wavelength method has
      the potential to provide accurate oxygen saturation measurements in arterial and
      venous blood, but experimental validation of the theory is still required to
      confirm this claim.

PMID- 19405776
TI  - Monte Carlo modeling of multilayer phantoms with multiple fluorophores:
      simulation algorithm and experimental validation.
AB  - This work is first a description of a statistical simulation algorithm developed
      for simulating the spectral absorption and emission of several fluorophores in an
      absorbing and diffusing multilayer model. Second, a detailed experimental
      validation of the simulation program is conducted on two sets of liquid and solid
      multilayer phantoms, containing one, two, or three fluorophores, within absorbing
      and scattering media. Experimental spatially resolved reflectance spectra are
      acquired in the wavelength band 400 to 800 nm and compared to corresponding
      simulated spectra. The degree of similarity between experimentation and
      simulation data is quantified. The results obtained underline good correlations
      with mean errors varying from 2 to 10%, depending on the number of layers and on
      the complexity of the phantom's composition.

PMID- 19405775
TI  - Photoacoustic tomography of the mouse cerebral cortex with a high-numerical
      aperture-based virtual point detector.
AB  - The mouse cerebral cortex was imaged in situ by photoacoustic tomography (PAT).
      Instead of a flat ultrasonic transducer, a virtual point detector based on a high
      numerical aperture (NA), positively focused transducer was used. This virtual
      point detector has a wide omnidirectional acceptance angle, a high sensitivity,
      and a negligible aperture effect. In addition, the virtual point detector can be
      located much more closely to the object during the detection. Compared with a
      finite-size flat transducer, images generated by using this virtual point
      detector have both uniform signal-to-noise ratio (SNR) and resolution.

PMID- 19405777
TI  - Line scan fluorescence correlation spectroscopy for three-dimensional
      microfluidic flow velocity measurements.
AB  - The flow direction of microfluidics in biological applications is not limited to
      two dimensions, but often extends to three dimensions. Currently there are
      optical methods available for the measurement of 3-D microfluidic flow vectors,
      but with low spatial resolution. Line scan fluorescence correlation spectroscopy
      (FCS) was proposed to determine flow directions in 2-D within microchannels and
      small blood vessels in our previous work. Importantly, its spatial resolution was
      demonstrated to be as good as 0.5 microm. In this work, we extend line scan FCS
      to the third dimension for the characterization of 3-D flow velocity vectors. The
      spatial resolution is close to the diffraction limit using a scan length of 0.5
      microm in all three dimensions. The feasibility of line scan FCS for 3-D
      microfluidic flow is verified by measurements in microchannels and small blood
      vessels of zebrafish embryos.

PMID- 19405778
TI  - Automatic algorithm for skin profile detection in photoacoustic microscopy.
AB  - We have developed an automatic algorithm to detect the skin profiles in the
      volumetric data acquired by photoacoustic microscopy for subcutaneous vasculature
      imaging. This algorithm analyzes the relationship between amplitudes of
      photoacoustic signals generated from the skin surface and underlying blood
      vessels to achieve a rough estimation of the skin profile. A better approximation
      of the skin profile is then acquired after nonparametric smoothing and Gaussian
      low-pass spatial filtering. An auto-fit scan mechanism is further developed based
      on the detected skin profile to achieve good ultrasonic focusing on the
      subcutaneous vessel layer when the skin contour variation is much larger than the
      ultrasonic focal zone. The importance of skin profile detection in calculating
      the maximum-amplitude-projection images and significantly improving the image
      quality by employing the auto-fit scan are demonstrated by in vivo experimental
      results.

PMID- 19405782
TI  - Antidepressants at environmentally relevant concentrations affect predator
      avoidance behavior of larval fathead minnows (Pimephales promelas).
AB  - The effects of embryonic and larval exposure to environmentally relevant (ng/L)
      concentrations of common antidepressants, fluoxetine, sertraline, venlafaxine,
      and bupropion (singularly and in mixture) on C-start escape behavior were
      evaluated in fathead minnows (Pimephales promelas). Embryos (postfertilization
      until hatching) were exposed for 5 d and, after hatching, were allowed to grow in
      control well water until 12 d old. Similarly, posthatch fathead minnows were
      exposed for 12 d to these compounds. High-speed (1,000 frames/s) video recordings
      of escape behavior were collected and transferred to National Institutes of
      Health Image for frame-by-frame analysis of latency periods, escape velocities,
      and total escape response (combination of latency period and escape velocity).
      When tested 12 d posthatch, fluoxetine and venlafaxine adversely affected C-start
      performance of larvae exposed as embryos. Conversely, larvae exposed for 12 d
      posthatch did not exhibit altered escape responses when exposed to fluoxetine but
      were affected by venlafaxine and bupropion exposure. Mixtures of these four
      antidepressant pharmaceuticals slowed predator avoidance behaviors in larval
      fathead minnows regardless of the exposure window. The direct impact of reduced C
      start performance on survival and, ultimately, reproductive fitness provides an
      avenue to assess the ecological relevance of exposure in an assay of relatively
      short duration.

PMID- 19405783
TI  - The toxicity of Roundup Original Max to 13 species of larval amphibians.
AB  - With the increased use of glyphosate-based herbicides (marketed under several
      names, including Roundup and Vision), there has been a concomitant increased
      concern about the unintended impacts that particular formulations containing the
      popular surfactant polyethoxylated tallowamine (POEA) might have on amphibians.
      Published studies have examined a relatively small number of anuran species
      (primarily from Australia and eastern North America) and, surprisingly, no
      species of salamanders. Using a popular formulation of glyphosate (Roundup
      Original Max), the goal of the present study was to conduct tests of lethal
      concentrations estimated to kill 50% of a population after 96 h (LC50(96-h)) on a
      wider diversity of species from both eastern and western North America. Tests
      were conducted on nine species of stage 25, larval anurans from three families
      (Ranidae: Rana pipiens, R. clamitans, R. sylvatica, R. catesbeiana, R. cascadae;
      Bufonidae: Bufo americanus, B. boreas; and Hylidae: Hyla versicolor, Pseudacris
      crucifer) and four species of larval salamanders from two families
      (Ambystomatidae: Ambystoma gracile, A. maculatum, A. laterale; and Salamandridae:
      Notophthalmus viridescens). For the nine species of larval anurans, LC50(96-h)
      values ranged from 0.8- to 2.0-mg acid equivalents per liter with relatively
      little pattern in differential sensitivity among the species or families. The
      four species of larval salamanders were less sensitive than the anurans, with
      LC50(96-h) values ranging from 2.7- to 3.2-mg acid equivalents per liter and no
      substantial differences among the species of salamanders. This work substantially
      increases the available data on amphibian sensitivity to glyphosate formulations
      that include either POEA surfactants or the equally moderately to highly toxic
      surfactants of Roundup Original Max and should be useful for improving future
      risk assessments.

PMID- 19405785
TI  - In vitro differentiation and attachment of human embryonic stem cells on
      periodontal tooth root surfaces.
AB  - Periodontal tissue engineering based on cell replacement therapies is a promising
      field for improved regeneration of tooth supporting structures lost as a result
      of destructive periodontal diseases. Human embryonic stem cells (hESCs) could
      become adequate cell source for tissue engineering because of their unlimited
      proliferative potential and ability to differentiate to all somatic cell types.
      The aim of this study was to analyze the differentiation capacity of hESCs toward
      periodontal compartment cells and their relationship with tooth root surfaces in
      vitro. Periodontal ligament fibroblastic cell (PDLF) cultures were established
      and characterized; hESCs (HUES-9 line) were expanded in undifferentiated state
      and characterized for pluripotency morphologically and immunohistochemically.
      Extracted tooth root slices (RS) of 300 microm thickness, prepared with both
      periodontal and endodontic instrumentation, were used. Three different
      experimental groups were established: (i) undifferentiated hESC colonies cultured
      on and around the RS; (ii) undifferentiated hESC colonies cultured on and around
      RS with PDLF coculture, and (iii) undifferentiated hESC colonies cultured on and
      around RS with PDLF coculture in osteoinductive medium for 3 weeks. The
      fibrogenic and osteogenic marker expression was assessed with
      immunohistochemistry; histological staining and scanning electron microscopy were
      utilized to determine the relationship between differentiating hESCs and
      mineralized tooth root structures. Results demonstrate that hESC differentiation
      is influenced by tooth structures, PDLFs, and osteogenic medium, resulting with
      increased propensity toward mesenchymal lineage commitment, and formation of soft
      hard tissue relationship in close contact areas. The proposed experimental system
      may facilitate further understanding in development of periodontal structures and
      contribute to realization of hESCs as a cell source in periodontal tissue
      engineering applications.

PMID- 19405784
TI  - Three-dimensional epithelial tissues generated from human embryonic stem cells.
AB  - The use of pluripotent human embryonic stem (hES) cells for tissue engineering
      may provide advantages over traditional sources of progenitor cells because of
      their ability to give rise to multiple cell types and their unlimited expansion
      potential. We derived cell populations with properties of ectodermal and
      mesenchymal cells in two-dimensional culture and incorporated these divergent
      cell populations into three-dimensional (3D) epithelial tissues. When grown in
      specific media and substrate conditions, two-dimensional cultures were enriched
      in cells (EDK1) with mesenchymal morphology and surface markers. Cells with a
      distinct epithelial morphology (HDE1) that expressed cytokeratin 12 and beta
      catenin at cell junctions became the predominant cell type when EDK1 were grown
      on surfaces enriched in keratinocyte-derived extracellular matrix proteins. When
      these cells were incorporated into the stromal and epithelial tissue compartments
      of 3D tissues, they generated multilayer epithelia similar to those generated
      with foreskin-derived epithelium and fibroblasts. Three-dimensional tissues
      demonstrated stromal cells with morphologic features of mature fibroblasts, type
      IV collagen deposition in the basement membrane, and a stratified epithelium that
      expressed cytokeratin 12. By deriving two distinct cell lineages from a common
      hES cell source to fabricate complex tissues, it is possible to explore
      environmental cues that will direct hES-derived cells toward optimal tissue form
      and function.

PMID- 19405786
TI  - Genotype-based therapeutic approach for colorectal cancer: state of the art and
      future perspectives.
AB  - BACKGROUND: There is a considerable need to increase efforts in maximizing
      clinical outcome in the treatment of colorectal cancer, and the identification of
      genetic factors underlying drug response seems to be one of the most promising
      areas in this research field. METHODS: Clinical trials and pharmacogenetic
      association studies were reviewed to offer an overview of the most commonly
      reported polymorphisms in candidate genes critically involved in the response to
      the chemotherapeutics used at present in the management of colorectal cancer.
      RESULTS: Several studies investigating the association between genotype and
      therapeutic results show contrasting data, thus determining increasing
      uncertainty in the identification of reliable predictive genetic markers of drug
      response. However, some of the genetic variations identified in genes encoding
      thymidylate synthase, dihydropyrimidine dehydrogenase, glutathione S-transferase
      pi, and uridine diphosphate glucosyltransferase 1A1 seem to be promising
      predictors of drug efficacy and/or toxicity. CONCLUSION: Additional investigation
      is needed to validate fully the clinical relevance of individual genetic
      differences in the variability of drug response. It is hoped that this knowledge
      base will offer, in the not too distant future, the opportunity to overcome the
      empirical trial-and-error method in favor of therapeutic drug optimization based
      on individual genetic make-up.

PMID- 19405787
TI  - Treatment strategies for Legionella infection.
AB  - Given the nonspecific clinical manifestations of Legionnaires' disease and the
      high mortality of untreated Legionnaires' disease, we recommend routine use of
      Legionella testing, especially the Legionella urinary antigen test, for all
      patients with community-acquired pneumonia. This includes patients with
      ambulatory pneumonia and hospitalized children. Legionella cultures should be
      more widely available, especially in hospitals where the drinking water is
      colonized with Legionella. Azithromycin or levofloxacin can be considered as
      first-line therapy. Other antibiotics including tetracyclines, tigecycline, other
      fluoroquinolones and other macrolides (especially clarithromycin) are also
      effective. The clinical response of quinolones may be somewhat more favorable
      compared to macrolides, but the outcome is similar. If the Legionnaires' disease
      is hospital-acquired, culturing of the hospital drinking water for Legionella is
      indicated.

PMID- 19405788
TI  - Pharmacotherapy for diabetic retinopathy.
AB  - BACKGROUND: Diabetic macular edema (DME) and proliferative diabetic retinopathy
      (PDR) continue to cause significant visual loss among patients with diabetes
      mellitus. In some patients unresponsive to standard laser techniques, as well as
      improved control of blood pressure and blood sugar, pharmacologic treatment may
      be beneficial. Although no agent is now approved by the FDA for this purpose,
      many agents are now being studied in randomized clinical trials (RCTs).
      OBJECTIVE: To review concisely the chief pharmacotherapies for diabetic
      retinopathy available at present. METHODS: Literature review and synopsis.
      RESULTS: Used alone, intravitreal triamcinolone acetonide (IVTA) seems to have
      some short-term efficacy against DME, but longer-term outcomes (< or = 3 years)
      using IVTA monotherapy showed a lesser benefit than focal/grid laser treatment in
      a prospective RCT done by the Diabetic Retinopathy Clinical Research Network.
      Intravitreal anti-VEGF agents have demonstrated some short-term efficacy against
      DME, and continuing RCTs will evaluate combination therapies (anti-VEGF and
      laser) for both DME and PDR. Other agents are being evaluated in pilot studies
      and Phase II RCTs. CONCLUSION: Pharmacotherapies for DME and PDR have potential
      for vision stabilization or improvement. Continuing RCTs will provide evidence
      based data on their role in clinical practice. A potential role for
      pharmacotherapy in the prevention of DME and PDR is also emerging.

PMID- 19405789
TI  - Treatment strategies for hot flushes.
AB  - BACKGROUND: Vasomotor symptoms are the most common complaints for which
      menopausal women seek medical care. Eighty per cent of all menopausal women will
      have hot flushes and night sweats, and of these 9% will have severe symptoms
      impacting their quality of life. Ideally, treatment should target the group most
      severely afflicted, and options for treatment should be tailored to each woman,
      since, for most women, vasomotor symptoms spontaneously resolve in 3 - 5 years.
      Recommendation at this time is for the shortest duration of therapy, which means
      that episodic review of therapy is indicated. OBJECTIVE: To review the latest
      literature investigating therapies for vasomotor symptoms and to discuss their
      effectiveness with emphasis on placebo-controlled, randomized clinical trials.
      METHODS: A literature search in PubMed for 'vasomotor symptoms', 'menopause
      symptoms', 'hot flushes', 'hot flashes' and 'night sweats' from 2003 to the
      present was performed. CONCLUSIONS: Estrogen remains the gold standard for
      treating vasomotor symptoms. As investigations into the physiology of hot flushes
      continue, centrally active drugs (selective serotonin or norepinephrine-serotonin
      reuptake inhibitors and gabapentin) have increased in use. The benefit from
      dietary herbal supplements is still inconclusive; however, recent studies have
      shown some mild response to soy and black cohosh.

PMID- 19405790
TI  - Treatment strategies for acute pulmonary embolism.
AB  - BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening condition that
      has been treated with anticoagulation for almost 50 years. OBJECTIVES: To review
      the current treatment options for PE and discuss recently published new features.
      METHODS: We reviewed literature involving the treatment strategies for venous
      thromboembolism (VTE) and in particular pulmonary embolism. Specific attention
      was drawn towards the evidence of the present treatment and of drugs being
      studied in Phase III trials. RESULTS/CONCLUSIONS: Treatment of acute PE consists
      of parenteral administration of heparin, low-molecular-weight heparin or
      fondaparinux overlapped and followed by oral vitamin K antagonists for a minimum
      of 3 months. Contemporary features include the emergence of new anticoagulant
      drugs such as oral synthetic inhibitors of thrombin or factor Xa. The duration of
      anticoagulation for unprovoked VTE remains highly debated.

PMID- 19405791
TI  - Treatment of acute bacterial exacerbations of chronic bronchitis.
AB  - BACKGROUND: Controversies persist regarding the optimal management of patients
      with acute exacerbations of chronic bronchitis (AECB). OBJECTIVE: To evaluate the
      available evidence on relevant issues, namely the need for administering
      antimicrobials in patients with AECB, the identification of the subgroup of
      patients with AECB needing antibiotics, the antimicrobial regimen of choice and
      its optimal duration, the existence of new agents, and the value of non
      antimicrobial regimens for AECB. METHODS: Data from various sources of evidence,
      including recent relevant meta-analyses, were appraised. CONCLUSION:
      Administration of antimicrobial agents, combined with bronchodilators and
      systemic corticosteroids, is warranted in approximately half of AECBs (i.e., in
      bacterial exacerbations) to achieve a survival benefit. Simple clinical
      parameters, mainly sputum purulence, and biomarkers, such as procalcitonin, are
      useful in identifying patients requiring antibiotics. Advanced antibiotics
      (quinolones, macrolides, or amoxicillin/clavulanic acid) are more effective than
      'old' antibiotics in AECB; regimens of short duration (for 5 days) are preferred.
      There is no difference between several classes of advanced antibiotics regarding
      their short-term effectiveness; however, quinolones are associated with better
      long-term outcomes than macrolides. Newer quinolones and new formulations of
      macrolides enrich clinicians' armamentarium against AECB.

PMID- 19405792
TI  - Treatment of the inflammatory myopathies: update and practical recommendations.
AB  - BACKGROUND: The inflammatory myopathies are a heterogeneous group of diseases
      including dermatomyositis, polymyositis, and inclusion body myositis. Clinical
      trials in myositis are rare, making it difficult to make clear recommendations on
      the treatment of these rare disorders. OBJECTIVE: To give an overview of
      treatment options and strategies and to provide the clinician with a framework
      that can be used in treating patients with myositis. METHODS: Results of clinical
      trials in myositis, case series and important case reports are presented and
      discussed. RESULTS/CONCLUSION: Most patients with dermatomyositis or polymyositis
      require treatment with oral high-dose prednisone combined with azathioprine or
      methotrexate to facilitate early tapering of prednisone. In case of treatment
      failure, intravenous immunoglobulin can be tried, followed by rituximab,
      mycophenolate mofetil, or tacrolimus depending on the specific clinical
      situation. A treatment trial with oral prednisone combined with methotrexate is
      advised in a subgroup of patients with inclusion body myositis.

PMID- 19405793
TI  - Treatment strategies for cystic fibrosis: what's in the pipeline?
AB  - Cystic fibrosis (CF) is an inherited disease, characterised by pancreatic
      malabsorption (with poor growth) and impaired mucociliary clearance (leading to
      recurrent pulmonary infection). The prognosis has markedly improved over the last
      40 years. This was achieved initially by improving pancreatic enzyme supplements
      and more recently through drugs designed to treat pulmonary infection, reduce
      inflammation and enhance mucociliary clearance. The CF gene has been sequenced,
      allowing new therapeutic targets to be identified. Currently the greatest
      therapeutic challenges are to correct the biochemical defect of CF and to
      identify effective treatments for chronic respiratory infection. This review
      provides an overview of CF, the treatment strategies currently used, and new
      drugs undergoing clinical trials.

PMID- 19405794
TI  - Management of complicated infections in the era of antimicrobial resistance: the
      role of tigecycline.
AB  - BACKGROUND: Increasing antimicrobial resistance and infection complications pose
      challenges to optimal antibiotic therapy. Paucity of new antibiotics (and the
      eventual bacterial resistance they face) highlights the critical need for more
      appropriate use of broadly effective agents, which may help to thwart the
      dramatic rise in global resistance. Single agents that can be combined
      effectively with others, if needed, promise the simplest overall utility.
      Approved in 2005 to treat complicated skin and intra-abdominal infections,
      tigecycline is a novel extended-spectrum minocycline derivative that circumvents
      bacterial resistance, as it is unaffected by efflux pumps and ribosomal
      protection. However, tigecycline should not be used as empiric monotherapy for
      treatment of health-care associated infections known or suspected to be owing to
      Pseudomonas aeruginosa or Proteus spp. OBJECTIVE: This article summarizes the
      demonstrated clinical utility of tigecycline so far. METHODS: A MEDLINE search
      examined authoritative published clinical studies, reviews and case reports
      detailing the clinical record of tigecycline since 2004. RESULTS/CONCLUSION:
      Tigecycline continues to maintain satisfactory profiles of safety, efficacy and
      antimicrobial resistance avoidance. Regardless, continued surveillance is needed
      to detect reduced susceptibility and resistance against both community and
      nosocomial pathogens. Judicious use of agents reserved for multidrug resistant
      pathogens is vital to preserve their effectiveness.

PMID- 19405795
TI  - Atopiclair.
AB  - BACKGROUND: MAS063DP cream has received marketing authorization in the USA and
      the EU as a medical device for the relief of symptoms of atopic dermatitis (AD)
      and contact dermatitis. OBJECTIVE: Review of technical and clinical data in the
      literature on MAS063DP to evaluate the role that MAS063DP (Sinclair
      Pharmaceuticals Ltd) holds in the management of patients affected by AD. METHODS:
      We explored the characteristics and efficacy of the product by a wide-ranging
      search of the medical and scientific studies in the literature and drew our
      conclusions also on the basis of our medical practice and knowledge concerning
      the treatment guidelines and therapy options of AD. CONCLUSION: MAS063DP is a
      product dermatologists could enroll in the treatment of signs and symptoms of
      mild-to-moderate AD in adult and pediatric patients.

PMID- 19405796
TI  - Itraconazole for severe asthma with fungal sensitivity.

PMID- 19405798
TI  - Transoral robotic surgery (TORS) in laryngeal and hypopharyngeal cancer.
AB  - OBJECTIVES: The current trend in managing laryngeal and hypopharyngeal cancer is
      to perform organ preservation therapy, which improves quality of life and
      decreases treatment-related morbidity. Transoral robotic surgery (TORS) can
      overcome the limit of "line of sight" often met in classic transoral procedure.
      We utilized a robotic surgical system to evaluate the feasibility and oncologic
      safety of transoral partial pharyngectomy and laryngectomy. MATERIALS AND
      METHODS: TORS was performed by using a "da Vinci surgical robot" (Intuitive
      Surgical, Inc., Sunnyvale, CA). An FK retractor (Gyrus Medical Inc., Maple Grove,
      MN) was used to expose the cancerous lesion transorally, and an endoscopic arm
      was introduced through the oral cavity with two instrument arms placed 30 degrees
      apart from the endoscopic arm. We performed TORS on 1 patient with pyriform sinus
      carcinoma and 4 patients with glottic carcinoma as a prospective human trial.
      RESULTS: Average surgical time measured was 39 minutes, including an average of
      25 minutes used for locating the robotic surgical system in place and exposing
      the lesion. TORS can provide a magnified three-dimensional view and overcome the
      limitation resulting from the "line of sight" that hinders the classic transoral
      procedure. All surgical resection margins were free of carcinoma. There were no
      perioperative complications, and also, no mortality due to the surgical
      procedure. CONCLUSIONS: This study demonstrates that the application of TORS for
      partial pharyngectomy and partial laryngectomy is technically feasible and safe.

PMID- 19405797
TI  - Correlation between gene expression and clinical data through linear and
      nonlinear principal components analyses: muscular dystrophies as case studies.
AB  - The large dimension of microarray data and the complex dependence structure among
      genes make data analysis extremely challenging. In the last decade several
      statistical techniques have been proposed to tackle genome-wide expression data;
      however, clinical and molecular data associated to pathologies have often been
      considered as separate dimensions of the same phenomenon, especially when
      clinical variables lie on a multidimensional space. A better comprehension of the
      relationships between clinical and molecular data can be obtained if both data
      types are combined and integrated. In this work we adopt a multidimensional
      correlation strategy together with linear and nonlinear principal component, to
      integrate genetic and clinical information obtained from two sets of dystrophic
      patients. With this approach we decompose different aspects of clinical
      manifestations and correlate these features with the correspondent patterns of
      differential gene expression.

PMID- 19405799
TI  - Peritoneal adhesions to prosthetic materials: an experimental comparative study
      of treated and untreated polypropylene meshes placed in the abdominal cavity.
AB  - BACKGROUND: Frequently, hernia repair requires polypropylene (PP) meshes, which
      carry a well-known adhesiogenic risk when placed in contact to the intestine. The
      aim of this experimental study in a rat model was to assess the role of some
      materials, when combined with PP, in preventing the adhesions' formation.
      MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were assigned to five
      groups for intraperitoneal mesh placement: untreated PP, PP+polyurethane (PP+PU),
      PP+Surgisis (PP+SIS), PP+expanded polytetrafluoroethylene (PP+ePTFE), and a
      control group without mesh. Twenty-one days and 3 and 6 months after the
      operation, an assessment of adhesion formation was performed, scoring adhesions
      in terms of extent and type and the adhesion index (AI; product of adhesions'
      extent and type). RESULTS: No significant difference was seen between PP+SIS,
      PP+PU, and control groups in adhesions extent/quality and in AI. The PP+SIS group
      had significantly lower adhesions' quality value and AI than PP+ePTFE. PP+PU had
      significantly lower adhesions' extent/quality value and AI than PP+ePTFE. The
      control group had adhesions with significantly lower extent/quality and AI than
      PP+ePTFE. The PP group had significantly more and denser adhesions, compared to
      PP+ePTFE, as well as a significantly higher AI. CONCLUSIONS: Adhesions' incidence
      is reduced by using treated PP meshes. PP+PU and PP+SIS were superior to PP+ePTFE
      in adhesion prevention.

PMID- 19405800
TI  - Novel approach of laparoscopic transperitoneal en bloc resection of urachal tumor
      and umbilectomy with a comparison of various techniques.
AB  - Urachal carcinoma is a rare cancer that accounts for less than 1% of all bladder
      cancers. Surgical resection remains the mainstay of treatment. With partial
      cystectomy, long-term survival is possible following complete resection of the
      tumor. In this paper, we describe a novel approach of laparoscopic en bloc
      partial cystectomy and umbilectomy. We emphasize the importance of complete
      resection of the tumor and umbilicus and prevention of tumor spillage during the
      procedure. The literature is also reviewed for the comparison of various
      laparoscopic techniques.

PMID- 19405801
TI  - Laparoscopic uterine vessels occlusion for the treatment of interstitial
      pregnancy.
AB  - Interstitial pregnancy is a rare form of ectopic pregnancy, but it results in
      significant maternal morbidity and mortality. In this paper, describe a case of
      interstitial pregnancy that was successfully managed by laparoscopic occlusion of
      the ipsilateral ascending branch of uterine artery and the communication of the
      ovarian artery. It would help to minimize the active bleeding and allow removing
      the gestation sac, placental tissue, and repair the interstitial tube. In this
      case, the operative bleeding was 80 mL only, and the operative time was 70
      minutes. The patient shared good postoperative recovery, and serum beta human
      chorionic gonadotropin decreased to below normal levels within 1 month after the
      operation. This procedure should be considered as a treatment option for
      unruptured interstitial pregnancy and may allow for conserving the patient's
      uterus and fallopian tube and preserving the future fertility.

PMID- 19405803
TI  - Laparoscopic gastric transposition with cervical esophagogastric anastomosis for
      long gap pure esophageal atresia.
AB  - The management of long-gap pure esophageal atresia remains controversial.
      Treatment options include primary repair with or without circular myotomoies of
      the upper pouch, proximal and distal pouch dilation/stretching, colon/small
      intestinal replacement, and gastric transposition/pull-up. Of these options, only
      the gastric transposition can be performed in a completely laparoscopic approach.
      In this paper, we report a case of complete laparoscopic gastric transposition
      with cervical esophagogastric anastomosis in an infant with long-gap pure
      esophageal atresia.

PMID- 19405802
TI  - Efficacy of periportal infiltration and intraperitoneal instillation of
      ropivacaine after laparoscopic surgery in children.
AB  - Postoperative pain is less intense after laparoscopic than after open surgery.
      However, minimally invasive surgery is not a a pain-free procedure. Many trials
      have been done in adults using intraperitoneal and/or incisional local
      anesthetic, but similar studies have not yet been reported in the literature in
      children. AIM: The aim of this study was to evaluate the analgesic effect of
      periportal infiltration and intraperitoneal instillation of ropivacaine in
      children undergoing laparoscopic surgery. MATERIALS AND METHODS: Thirty patients
      who underwent laparoscopic surgery were randomly allocated to one of three
      groups. Group A (n = 10) received local infiltration of port sites with 10 mL of
      ropivacaine. Group B (n = 10) received both an infiltration of port sites with 10
      mL of ropivacaine and an intraperitoneal instillation of 10 mL of ropivacaine.
      Group C did not receive any analgesic treatment. The local anesthetic was always
      administered at the end of surgery. The degree of postoperative abdominal
      parietal pain, abdominal visceral pain, and shoulder pain was assessed by using a
      Wong-Baker pain scale and a Visual Analog Scale (VAS) at 3, 6 12, and 24 hours
      postoperatively. The following parameters were also evaluated: rescue analgesic
      treatment, length of hospital stay, and time of return to normal activities.
      RESULTS: Three hours after operation, patients had low pain scores. Six and 12
      hours postoperatively, the abdominal parietal pain was significantly higher (P <
      0.0005) in group C than in the other two groups, both treated with an
      infiltration at the trocar sites; mean intensity of abdominal visceral pain was
      significantly lower (P < 0.0005) in group B than in groups A and C; the overall
      incidence of shoulder pain was significantly lower (P < 0.0005) in group B
      patients than in patients of groups A and C. At 20 hours postoperatively, pain
      scores were significantly reduced of intensity in all groups. Rescue analgesic
      treatment was significantly higher in group C, if compared to groups A and B 12
      hours after the operation. No statistically significant difference was found in
      length of hospital stay, but children who received analgesic treatment had a more
      rapid return to normal activities than untreated patients (P < 0.0005).
      CONCLUSIONS: Our study demonstrates that the combination of local infiltration
      and intraperitoneal instillation of ropivacaine is more effective for pain relief
      in children after laparoscopic surgery than the administration of ropivacaine
      only at the trocar sites.

PMID- 19405804
TI  - Laparoscopic removal of a gastric trichobezoar in a pediatric patient.
AB  - Trichobezoars from the ingestion of hair typically develop into a large,
      spherical foreign body within the stomach. Due to the frequently large size,
      endoscopic removal is usually not feasible beyond diagnosis. Likewise, the size
      often has forced surgeons to remove these trichobezoars via laparotomy.
      Laparoscopic removal of gastric trichobezoars has been reported, but the concern
      with this technique is that the complete removal of the large bezoar without
      spillage of hairs in the peritoneal cavity may be difficult. As such, most of the
      reports are laparoscopic assisted, but still utilize an extended incision to
      facilitate direct removal from the peritoneal cavity. In this case, we describe
      in this paper the complete laparoscopic removal of a giant trichobezoar in a 10
      year-old child without spillage, using piecemeal removal through the umbilical
      incision without extending the incisions.

PMID- 19405805
TI  - Combined laparoscopic cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy in a patient with peritoneal mesothelioma.
AB  - The role of minimally invasive, laparoscopic hyperthermic intraperitoneal
      chemotherapy (HIPEC) has been reported by several centers around the world,
      mainly to palliate intractable ascites in patients with extensive peritoneal
      surface malignancies who are not candidates for a complete cytoreduction. In this
      paper, we report on the first case of combined laparoscopic cytoreductive surgery
      and HIPEC with curative intent in a patient with limited peritoneal mesothelioma.

PMID- 19405806
TI  - Diagnostic characteristics of given video capsule endoscopy in diagnosis of
      celiac disease: a meta-analysis.
AB  - BACKGROUND AND AIMS: In the view of small sample sizes of the studies published
      so far, the value of video capsule endoscopy (VCE) in diagnosing celiac disease
      (CD) is yet to be determined. The aim of this work was to systemically determine
      the overall diagnostic characteristics of VCE in diagnosing noncomplicated CD,
      compared to the gold standard, using meta-analysis. PATIENTS AND METHODS: An
      extensive literature search was performed looking for prospective, controlled
      trials, with investigators blinded to results of the pathology of small-bowel
      biopsies. Two independent authors performed data extraction and assessment of the
      methodologic quality of each trial. Diagnostic characteristics of each trial were
      collected, and pooled sensitivity, specificity, likelihood ratios, and diagnostic
      odds ratios were computed. Description of complications and costs was included,
      if reported. RESULTS: A total of three studies met the inclusion criteria (n =
      107; 63 with CD and 44 without). The overall pooled VCE sensitivity was 83% (95%
      confidence interval [CI] = 71-90%) and specificity was 98% (95% CI = 88-99.6%).
      No major complications were reported. The costs were mentioned only in one study.
      CONCLUSIONS: The overall diagnostic characteristics of VCE, when used to diagnose
      celiac disease, though good with an experienced eye, could not justify the
      routine use of VCE as an alternative to the pathology of small-bowel biopsies.
      More studies are needed with proper cost-benefit analysis.

PMID- 19405807
TI  - Laparoscopic proximal Roux-en-Y gastrojejunal diversion in children: preliminary
      experience from a single center.
AB  - BACKGROUND: Neurologically impaired children (NIC) have a high risk of recurrence
      of gastroesophageal reflux (GER) following fundoplication. A postpyloric feeding
      tube may be useful when gastric emptying disorders occur; however, dislocation
      and difficulty in feeding management often require more aggressive procedures.
      Total esophagogastric dissociation (Bianchi's TEGD) is an alternative to the
      classic fundoplication procedure, whereas laparoscopic gastric bypass is a
      frequently performed procedure in morbid obesity, improving gastric outlet. AIM:
      The aim of this paper is to present a preliminary experience on the laparoscopic
      Roux-en-Y gastrojejunal bypass, associated with Nissen fundoplication and
      gastrostomy, to treat and prevent GER in NIC with gastric emptying disorders.
      MATERIALS AND METHODS: Eight neurologically impaired children underwent surgical
      treatment because of feeding problems and pulmonary complications. The procedure
      included: 1) hiatoplasty, 2) Nissen fundoplication, 3) 20-cm Roux-en-Y
      gastrojejunal anastomosis and jejuno-jejunal anastomosis, and 4) gastrostomy.
      RESULTS: All cases were fed on postoperative day 3 without any intraoperative
      complications. One case developed an obstruction of the distal anastomosis due to
      adhesion and needed reoperation. Outcome was clinically evaluated with serial
      upper gastrointestinal contrast studies and endoscopies. CONCLUSIONS:
      Laparoscopic proximal Roux-en-Y gastrojejunal diversion, without gastric
      resection, is a safe, feasible procedure that improves gastric emptying and
      reduces the risk of GER recurrence. Yet, long-term results still have to be
      evaluated.

PMID- 19405808
TI  - Successful laparoscopic treatment of hemorrhage from ileal duplication cyst in a
      10-year-old Saudi boy.
AB  - Lower gastrointestinal hemorrhage often produces diagnostic difficulty in
      children. Endoscopy, radionuclide scans, computed tomography/magnetic resonance
      angiography, and conventional angiography have been the usual armamentarium for
      locating the site of bleeding. In recent times, laparoscopy has offered an
      effective tool for diagnosing various intra-abdominal, especially extraluminal,
      pathologies elusive to other modalities of diagnosis. In this paper, we present a
      case of massive hemorrhage from an ileal duplication cyst in a 10-year-old Saudi
      boy diagnosed and treated by laparoscopy. We believe this is the first such
      reported case from the Kingdom of Saudi Arabia.

PMID- 19405809
TI  - NOTES performed using multiple ports of entry: Current experience and potential
      implications for urologic applications.
AB  - An isolated transgastric port raises serious limitations in performing natural
      orifice translumenal endoscopic surgery (NOTES) complex procedures in the urology
      field. In an attempt to overcome these limitations, several solutions has been
      advanced, such as the hybrid approach (adding a single abdominal port access) or
      the pure NOTES combined approach (joining multiple natural orifice ports). To
      review the current state of experimental and clinical results of multiple ports
      in NOTES, a literature search of PubMed was performed, seeking publications from
      January 2002 to 2008 on NOTES. In addition, we looked at pertinent abstracts of
      annual meetings of the American Urological Association, the European Association
      of Urology, and the World Congress of Endourology from 2007. Multiple ports of
      entry seem to be necessary, mainly for moderately complex procedures. Thus, we
      could find studies using the hybrid approach (combination of transgastric or
      transvaginal access with a single transabdominal port), or using the pure NOTES
      combined approach (transgastric and transvesical, transvaginal and transcolonic,
      or transgastric and transvaginal). There is still limited experience in humans
      using these approaches, and no comparative studies exist to date. It is
      predictable that for moderately complex procedures, we will need multiple ports,
      so the transvaginal-transabdominal (hybrid) approach is the most appealing,
      whereas in a pure NOTES perspective, the transgastric-transvesical approach seems
      to be the preferred approach. We are waiting for new equipment and instruments
      that are more appropriate for these novel techniques.

PMID- 19405812
TI  - Age-associated decrease of high-density lipoprotein-mediated reverse cholesterol
      transport activity.
AB  - High-density lipoproteins (HDL) are considered atheroprotective in contrast to
      low-density lipoproteins (LDL), which are atherogenic in their oxidized form. A
      growing body of evidence suggests that HDL exert part of their antiatherogenic
      effect by counteracting LDL oxidation as well as their proinflammatory effect.
      However, a number of studies, carried over the past 30 years, have shown that
      cholesterol efflux plays a major role in the atheroprotective effects of HDL and
      cholesterol homeostasis. These studies have further identified the scavenger
      receptor type B-I (SR-BI), the adenosine triphosphate (ATP)-binding cassette
      transporters ATP-binding cassette subfamily A1 (ABCA1), ATP-binding cassette
      subfamily G1 (ABCG1) and ABCG4, the liver X receptor/retinoid X receptor
      (LXR/RXR) and peroxisome proliferator-activated receptorgamma(PPAR gamma)
      transcription factors, the HDL components apolipoprotein A-I (apoA-I), lecithin
      cholesterol acyltransferase (LCAT), and phospholipids as additional mediators of
      cholesterol transport. Cholesterol efflux occurs via three independent pathways:
      (1) aqueous diffusion, (2) nonspecific efflux via SR-BI receptors, and (3)
      specific efflux via cholesterol-responsive members of the ABC superfamily.
      Whereas aqueous diffusion and scavenger receptor class B, type I (SR-BI)-mediated
      efflux transport free cholesterol to a wide variety of cholesterol acceptors
      (particles containing phospholipids, HDL, and lipidated apo-lipoproteins; LDL,
      etc), the ABCA1 pathway mediates the transport of cholesterol in a unidirectional
      manner, mainly to lipid-poor apoA-I. In contrast, the ABCG1 pathway is
      responsible for the transport of cholesterol to all the subfamily members of HDL.
      Although HDL-mediated cholesterol efflux is apoA-I-dependent, recent studies have
      suggested an involvement of the enzyme paraoxonase 1 (PON1). Cholesterol efflux
      is carried on by a number of factors such as genetic mutations, smoking, stress,
      and high-fat diets. It is attenuated with aging due to changes in the composition
      and structure of HDL, especially the phosphatidylcholine/sphingomyelin ratio, the
      fluidity of the phospholipidic layer, the concentration of apoA-I, and the
      activity of PON1. This review summarizes the findings that cholesterol
      homeostasis is disrupted with aging as a consequence of dysfunctional cholesterol
      efflux and the impairment of physiological functions.

PMID- 19405811
TI  - Women's opinions about routine HIV testing during pregnancy: implications for the
      opt-out approach.
AB  - The 1995 United States Public Health Service (USPHS) recommendation regarding HIV
      testing for pregnant women was revised in 2003 calling for routine HIV testing
      for pregnant women with patient notification. Routine testing (opt-out screening)
      offers women the opportunity to decline HIV testing but eliminates the
      requirement of pretest counseling and separate written consent. To assess women's
      opinions about the opt-out approach to HIV testing during pregnancy, a cross
      sectional survey was conducted in May-June 2004 at 14 geographically diverse
      clinics funded by Ryan White CARE Act (RWCA) Part C and Part D agreements. Of 853
      women respondents to the one-page, self-completed survey questionnaire, 90%
      agreed with routine HIV testing and 91% reported being comfortable with testing,
      demonstrating that the large majority of women agree with and support HIV testing
      as a part of routine prenatal care. Women's opinions were associated with HIV
      testing status, e.g., 76% of women who had never been tested for HIV thought HIV
      testing should be part of a routine pregnancy check-up as compared with women who
      were HIV-negative (93%) or HIV-positive (90%) (chi(2) = 31.3943, p < 0.0001).
      Comfort with HIV testing was associated with higher HIV knowledge. Approximately
      half of the respondents indicated that HIV tests are different from other tests
      and that women need more information prior to testing. Results demonstrated clear
      consensus in support of routine testing. Increased efforts to disseminate
      resources to providers coupled with providers' effective communication of
      information to pregnant women can build on the support that women have conveyed
      for HIV testing during pregnancy.

PMID- 19405813
TI  - Adeno-associated virus-8-mediated intravenous transfer of myostatin propeptide
      leads to systemic functional improvements of slow but not fast muscle.
AB  - Myostatin is a member of the transformating growth factor-beta (TGF-beta)
      superfamily of proteins and is produced almost exclusively in skeletal muscle
      tissue, where it is secreted and circulates as a serum protein. Myostatin acts as
      a negative regulator of muscle mass through the canonical SMAD2/3/4 signaling
      pathway. Naturally occurring myostatin mutants exhibit a 'double muscling'
      phenotype in which muscle mass is dramatically increased as a result of both
      hypertrophy and hyperplasia. Myostatin is naturally inhibited by its own
      propeptide; therefore, we assessed the impact of adeno-associated virus-8 (AAV8)
      myostatin propeptide vectors when systemically introduced in MF-1 mice. We noted
      a significant systemic increase in muscle mass in both slow and fast muscle
      phenotypes, with no evidence of hyperplasia; however, the nuclei-to- cytoplasm
      ratio in all myofiber types was significantly reduced. An increase in muscle mass
      in slow (soleus) muscle led to an increase in force output; however, an increase
      in fast (extensor digitorum longus [EDL]) muscle mass did not increase force
      output. These results suggest that the use of gene therapeutic regimens of
      myostatin inhibition for age-related or disease-related muscle loss may have
      muscle-specific effects.

PMID- 19405814
TI  - A comprehensive review on mesenchymal stem cell growth and senescence.
AB  - In recent years mesenchymal stem cells (MSCs) have generated a great deal of
      excitement as an attractive alternative to embryonic stem cells (ESCs) in cell
      based regenerative medicine. In contrast to cells of embryonic origin, however,
      the clinical application of MSCs is heavily restricted by their finite ability of
      self-renewal, in which they resemble the rest of the somatic cells. Yet the
      mechanisms controlling MSC proliferation and senescence remain unclear. This
      review summarizes recent advances in our understanding of the factors affecting
      MSC expansion in vitro and discusses the pattern of their senescence with
      particular emphasis on the role of telomere shortening, activation of effectory
      pathways, and oxidative stress. The issues associated with MSC growth and
      senescence will be shown in the context of other somatic cells, and all of the
      parallels and disparities will be delineated precisely.

PMID- 19405815
TI  - Transcolonic NOTES: Current experience and potential implications for urologic
      applications.
AB  - There has been a progressive evolution in the field of surgery over the past 100
      years-from the invasive open laparotomy to increasing less invasive techniques of
      laparoscopy. Conversely, the field of gastrointestinal endoscopy has witnessed a
      surge in increasingly more interventional techniques, previously only in the
      realm of gastrointestinal surgery, such as transgastric pseudocyst drainage and
      transgastric endoscopic pancreatic debridement. Natural orifice translumenal
      endoscopic surgery (NOTES) may represent a convergence and collaboration of the
      two fields and a paradigm shift in the concepts of both minimally invasive
      surgery and interventional endoscopy. NOTES involves performance of intra
      abdominal surgical procedures via an incisional opening through a natural orifice
      (mouth, anus, vagina, or urethra). Although early studies focused on the
      transgastric approach, there has been increasing numbers of NOTES procedures
      reported via the transcolonic, transvaginal, and transvesical approach. While
      further research needs to be undertaken to evaluate the feasibility, safety, and
      applicability of NOTES in a clinical setting, it has the potential to become an
      integral facet of minimally invasive intra-abdominal surgery in the future. In
      particular, given the trend in urology toward increasing minimally invasive
      techniques, NOTES embodies the next incremental step needed to further reduce
      patient morbidity and procedural trauma in urologic interventions. This article
      will explore the transcolonic approach to the peritoneal cavity.

PMID- 19405816
TI  - Journal of Endourology. Preface.

PMID- 19405817
TI  - Effect of Er,Cr:YSGG laser parameters on shear bond strength and microstructure
      of dentine.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of different
      Er,Cr:YSGG laser parameters on the morphology of irradiated dentine and the shear
      bond strength between resin composites and irradiated dentine. MATERIALS AND
      METHODS: Dentine specimens prepared from extracted human third molars were
      randomly assigned to six groups, including one receiving phosphoric acid etching,
      and five others with different laser parameters: 5 W for 30 sec, 2.5 W for 30
      sec, 2.5 W for 60 sec, 1.5 W for 30 sec, and 1.5 W for 100 sec. Surface
      morphology was examined using a scanning electron microscope (SEM). Average
      roughness (Ra) was determined with a profilometer. Bonding of resin composites to
      the dentine specimens was tested in shear mode. RESULTS: The dentine surfaces
      irradiated by the Er,Cr:YSGG laser showed a scaly and rugged appearance and open
      dentinal tubules without smear layer production. The 5-W-irradiated group had the
      highest roughness value (p < 0.05). One-way ANOVA revealed that the shear bond
      strength of resin composites to the laser-irradiated dentine ranged from 12.35
      15.61 MPa, and was not significantly (p > 0.05) different from the bond strength
      seen in the acid-etched dentine of 19.06 MPa. However, the surface roughness of
      the laser-irradiated dentine was significantly (p < 0.05) higher than that of the
      acid-etched dentine. CONCLUSIONS: The 5-W power setting may be suitable for
      dental restoration applications in terms of shear bond strength and activation
      area.

PMID- 19405818
TI  - Wound healing with PRGF infiltration in CO(2) laser lesions of the tongue: an
      animal study.
AB  - OBJECTIVE: This study was done of the effects of plasma rich in growth factors
      (PRGF) on the healing of tongue wounds induced by the CO(2) laser. MATERIALS AND
      METHODS: A prospective blind study was made of 60 Sprague-Dawley rats divided
      into two groups after the creation of tongue lesions using the CO(2) laser.
      Nothing was applied to the resulting wounds in the first group, while PRGF was
      applied to the 30 wounds in the second group. Wound re-epithelialization and
      inflammation were measured after 7, 14, and 28 d. RESULTS: No significant
      differences were seen between the two groups in relation to wound re
      epithelialization, and the group without PRGF actually showed significantly
      better resolution of the inflammatory process after 14 d (p = 0.036).
      CONCLUSIONS: After 28 d, the rat tongue wounds produced by the CO(2) laser showed
      complete healing, independently of PRGF application.

PMID- 19405819
TI  - Evaluation of the surface roughness and morphologic features of Y-TZP ceramics
      after different surface treatments.
AB  - OBJECTIVE: This study aimed to investigate the effect of different energy
      intensities of the Er:YAG laser and of air abrasion with Al(2)O(3) particles on
      the surface roughness and morphologic characteristics of yttrium-stabilized
      tetragonal zirconia (Y-TZP) ceramics. BACKGROUND DATA: Surface roughness enhances
      the micromechanical interlocking of luting agents to ceramic surfaces. However,
      the most appropriate surface treatment for Y-TZP ceramics has yet to be
      determined. MATERIALS AND METHODS: Two Y-TZP materials were evaluated: Cercon
      Smart Ceramics and Procera Zirconia. Thirty plates from each ceramic material
      were randomly divided into five groups according to the surface treatment
      received (none [control], air abrasion, or irradiation with the Er:YAG laser at
      three different energy intensities [200, 400, or 600 mJ]). After the surface
      treatments, the ceramic plates were gold-coated and their surface roughness (Ra,
      microm) was measured using confocal microscopy. For each ceramic system, the
      surface roughness was analyzed through two-way ANOVA/Tukey's test, with a 5%
      significance level. Changes in the morphological characteristics of the ceramics
      were examined through light and scanning electron microscopy. RESULTS: For both
      zirconia-based materials, irradiation with 400 mJ or 600 mJ increased surface
      roughness and provided significant morphological changes. Air-abraded Cercon
      surfaces were rougher compared to the ones irradiated with 200 mJ of laser
      energy, whereas Procera surfaces irradiated with 200 mJ were rougher than the air
      abraded ones. CONCLUSIONS: Higher laser power settings (400 and 600 mJ) cause
      excessive material deterioration, making them unsuitable as surface treatments
      for zirconia surfaces. Irradiation with 200 mJ provides mild surface alterations,
      with intermediary features between the effects of air abrasion and higher laser
      intensities.

PMID- 19405820
TI  - Update on the changing numbers and distribution of periodontists.
AB  - A review of the 2006 and past American Dental Association (ADA) studies on the
      distribution of dentists provides information on the evolving number of
      periodontists. Despite an overall increase in the number of periodontists, major
      differences continue in practitioner/population ratios in different geographic
      areas. As in past reviews, suggestions are offered for efforts by the ADA and/or
      the American Academy of Periodontology to draw attention to the limited numbers
      of periodontists in particular regions and states; to increase efforts to educate
      the public on the need and value of periodontal services; and to increase the
      profession's awareness of the growing diversity in the nation's population and
      the need to modify and adjust its efforts to attract underserved populations with
      different familial, cultural, and educational backgrounds.

PMID- 19405822
TI  - Author's Response: Re: Finkelman RD. Letter to the Editor: Re: "Clinical
      Guidelines of the Italian Society of Periodontology for the Reconstructive
      Surgical Treatment of Angular Bony Defects in Periodontal Patients".

PMID- 19405823
TI  - Re: a pilot study to evaluate a tissue-engineered bilayered cell therapy as an
      alternative to tissue from the palate.

PMID- 19405825
TI  - A prospective multicenter 5-year radiographic evaluation of crestal bone levels
      over time in 596 dental implants placed in 192 patients.
AB  - BACKGROUND: Dental implants have been used to replace missing teeth to provide
      function and esthetics. One goal of such restorations is to maintain host tissue
      around the implants. The purpose of this prospective multicenter human clinical
      trial was to evaluate radiographic marginal bone levels around non-submerged
      hollow cylindrical and solid-screw implants for 5 years after loading. METHODS:
      Patients older than 18 years of age with sufficient native bone to surround a
      dental implant without imposing on a vital structure were recruited at five
      sites. Solid-screw or hollow-cylinder implants with a titanium plasma-sprayed
      implant surface were placed in the anterior maxilla or anterior mandible and
      restored with fixed restorations. Baseline radiographs were taken at the time of
      implant placement. Subsequent radiographs were taken at the time of final
      prosthesis placement, at 6 months after prosthesis placement, and annually from
      prosthesis placement for 5 years. RESULTS: The results of 596 implants in 192
      patients at five international sites revealed that clinically significant
      remodeling of the marginal bone occurred during the first 6 months after implant
      placement, with a mean (+/- SD) marginal bone loss of 2.44 +/- 1.20 mm. After
      that, clinically insignificant mean changes in the bone were observed. Overall,
      0.22 +/- 0.42 mm of bone loss occurred between the time of prosthesis placement
      and 1-year postloading. Between 1-year postloading and the last 5-year recall,
      0.18 +/- 0.88 mm bone loss occurred. Because 2.84 +/- 1.63 mm of bone loss
      occurred between implant placement and the 5-year postloading follow-up, 86% of
      the total mean bone loss over the course of 5 years was accounted for at the time
      of prosthesis placement. These same trends occurred if the data were analyzed
      with regard to implant design (solid screw and hollow cylinder), type of
      restoration (single and multiple), and length of implant (8 to 10, 12, and 14 to
      16 mm). CONCLUSIONS: These data demonstrate that, in general, clinically
      significant marginal bone remodeling occurred between the time of implant
      placement and final prosthesis placement around one-stage non-submerged titanium
      implants with a titanium plasma-sprayed surface. Subsequent to that, bone loss
      observed around implants up to 5 years postloading was minimal. These results
      suggest that the factors that influence early healing around implants are
      significantly different from those that affect later marginal bone remodeling.

PMID- 19405826
TI  - Temporal association of elevated C-reactive protein and periodontal disease in
      men.
AB  - BACKGROUND: Most studies on the relationship between serum C-reactive protein
      (CRP) and periodontal disease have been cross-sectional. In this study, we
      investigated the temporal association between CRP and periodontal disease by
      following a large number of subjects for 1 year. METHODS: We studied 11,162 men
      in Nagoya, Japan, who had an initial dental examination as part of a complete
      physical examination and then underwent the same examination 1 year later. For
      the 4,997 men without periodontal disease at baseline, logistic regression
      analysis was performed to examine the relationship between baseline CRP and
      periodontal disease 1 year later, adjusting for age, body mass index,
      glycosylated hemoglobin A1c level, and smoking status. Similarly, logistic
      regression analysis was performed to examine the relationship between periodontal
      disease at baseline and CRP 1 year later for the 10,376 men with normal baseline
      CRP, adjusting for the same confounding factors. RESULTS: Among men without high
      CRP at baseline, periodontal disease at baseline correlated to CRP 1 year later.
      The odds ratio was 1.336 (95% confidence interval [CI]: 1.115 to 1.674). However,
      in the men without periodontal disease, no significant correlations were seen
      with baseline CRP or periodontal disease 1 year later. The odds ratio was 1.163
      (95% CI: 0.894 to 1.513). CONCLUSION: Periodontal disease increased the risk for
      high serum CRP levels in men after 1 year of follow-up.

PMID- 19405827
TI  - The relationship between serum lipids and periodontitis in elderly non-smokers.
AB  - BACKGROUND: There are common risk factors for periodontal disease and
      cardiovascular disease in elderly patients. Some studies reported that a low
      total cholesterol (TC) serum level is associated with a higher level of death in
      the elderly. The purpose of this study was to investigate the relationship
      between serum lipids and periodontal disease in non-smoking elderly patients.
      METHODS: Two hundred thirty-four non-smokers (63 males and 171 females)
      participated in this study. Multiple regression analysis was performed to
      evaluate the relationship between serum lipids and periodontitis and between
      serum lipids and inflammatory factors. The percentage of sites with probing depth
      (PD) > or =4 mm, clinical attachment level (CAL) > or =4 mm, and bleeding on
      probing (BOP) were used as dependent variables. TC, high-density lipoprotein
      cholesterol (HDL-C), gender, and the number of teeth present were included in the
      model as independent variables in the first analysis. TC, HDL-C, and low-density
      lipoprotein cholesterol (LDL-C) were used as dependent variables. Albumin,
      inorganic phosphorus, calcium, and C-reactive protein were used as independent
      variables in the second analysis. RESULTS: According to the results of the
      multiple linear regression analysis, TC was associated with the percentage of
      sites with PD > or =4 mm (P <0.01; beta = -0.19), CAL > or =4 mm (P <0.01; beta =
      -0.20), and BOP (P = 0.03; beta = -0.16). HDL-C and LDL-C have a significant
      association with inflammatory markers and inorganic phosphorus and calcium,
      respectively. CONCLUSION: Higher TC is associated with a lower prevalence of
      periodontitis in non-smoking elderly patients.

PMID- 19405828
TI  - Clinical features of early periodontitis.
AB  - BACKGROUND: Most of the evidence on periodontitis in young individuals originates
      in case series or case-control studies of poor quality. We investigated the
      intraoral distribution of clinical attachment level (CAL) and probing depth (PD)
      and the associations between the oral hygiene parameters and the signs of
      periodontitis (CAL and PD) in adolescents. METHODS: This study consisted of 87
      cases presenting with CAL > or =3 mm in at least two of the 16 teeth recorded and
      73 non-cases who did not fulfill this inclusion criterion, nested in a fully
      enumerated adolescent population, who were screened for signs of periodontitis.
      The 160 subjects were reexamined by a single trained and calibrated periodontist.
      The intraoral patterns of periodontal destruction were described graphically.
      RESULTS: Cases had more supragingival plaque, more supragingival calculus, and
      more bleeding on probing than non-cases. The intraoral patterns of periodontal
      destruction were similar in cases and non-cases. The site-specific associations
      between the putative determinants supragingival plaque, supragingival calculus,
      and bleeding on probing and the signs of periodontal destruction were highly
      positive. CONCLUSION: The results of this study lend little support to the notion
      that a particular intraoral pattern of breakdown is specific to young cases of
      severe periodontitis, nor do the results support the view that destruction is
      incommensurate with oral hygiene parameters.

PMID- 19405829
TI  - The impact of the stone age diet on gingival conditions in the absence of oral
      hygiene.
AB  - BACKGROUND: The objective of this study was to assess the oral microbiota and
      clinical data in subjects without access to traditional oral hygiene methods and
      who ate a diet available in the Stone Age. METHODS: Ten subjects living in an
      environment replicating the Stone Age for 4 weeks were enrolled in this study.
      Bleeding on probing (BOP), gingival and plaque indices, and probing depth (PD)
      were assessed at baseline and at 4 weeks. Microbiologic samples were collected at
      the mesio-buccal subgingival aspects of all teeth and from the dorsum of the
      tongue and were processed by checkerboard DNA-DNA hybridization methods. RESULTS:
      No subject had periodontitis. Mean BOP decreased from 34.8% to 12.6% (P <0.001).
      Mean gingival index scores changed from 0.38 to 0.43 (not statistically
      significant) and mean plaque scores increased from 0.68 to 1.47 (P <0.001). PD at
      sites of subgingival sampling decreased (mean difference: 0.2 mm; P <0.001). At
      week 4, the total bacterial count was higher (P <0.001) for 24 of 74 species,
      including Bacteroides ureolyticus, Eikenella corrodens, Lactobacillus
      acidophilus, Capnocytophaga ochracea, Escherichia coli, Fusobacterium nucleatum
      naviforme, Haemophilus influenzae, Helicobacter pylori, Porphyromonas
      endodontalis, Staphylococcus aureus (two strains), Streptococcus agalactiae,
      Streptococcus anginosis, and Streptococcus mitis. Bacterial counts from tongue
      samples were higher at baseline (P <0.001) for 20 species, including Tannerella
      forsythia (previously T. forsythensis), Aggregatibacter actinomycetemcomitans
      (previously Actinobacillus actinomycetemcomitans; serotype a), and Streptococcus
      spp. CONCLUSIONS: The experimental gingivitis protocol is not applicable if the
      diet (e.g., Stone Age) does not include refined sugars. Although plaque levels
      increased, BOP and PD decreased. Subgingival bacterial counts increased for
      several species not linked to periodontitis, whereas tongue bacterial samples
      decreased during the study period.

PMID- 19405830
TI  - Biologic assessment of antiseptic mouthwashes using a three-dimensional human
      oral mucosal model.
AB  - BACKGROUND: The biologic safety profile of oral health care products is often
      assumed on the basis of simplistic test models such as monolayer cell culture
      systems. We developed and characterized a tissue-engineered human oral mucosal
      model, which was proven to represent a potentially more informative and more
      clinically relevant alternative for the biologic assessment of mouthwashes. The
      aim of this study was to evaluate the biologic effects of alcohol-containing
      mouthwashes on an engineered human oral mucosal model. METHODS: Three-dimensional
      (3D) models were engineered by the air/liquid interface culture technique using
      human oral fibroblasts and keratinocytes. The models were exposed to phosphate
      buffered saline (negative control), triethylene glycol dimethacrylate (positive
      control), cola, and three types of alcohol-containing mouthwashes. The biologic
      response was recorded using basic histology; a cell proliferation assay; 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tissue-viability assay;
      transmission electron microscopy (TEM) analysis; and the measurement of release
      of interleukin (IL)-1beta by enzyme-linked immunosorbent assay. RESULTS:
      Statistical analysis showed that there was no significant difference in tissue
      viability among the mouthwashes, cola, and negative control groups. However,
      exposure to the positive control significantly reduced the tissue viability and
      caused severe cytotoxic epithelial damage as confirmed by histology and TEM
      analysis. A significant increase of IL-1beta release was observed with the
      positive control and, to a lesser extent, with two of the tested mouthrinses.
      CONCLUSIONS: The 3D human oral mucosal model can be a suitable model for the
      biologic testing of mouthwashes. The alcohol-containing mouthwashes tested in
      this study do not cause significant cytotoxic damage and may slightly stimulate
      IL-1beta release.

PMID- 19405831
TI  - Comparison of dermal matrix and polytetrafluoroethylene membrane for socket bone
      augmentation: a clinical and histologic study.
AB  - BACKGROUND: Remodeling and resorption of the alveolar crest, specifically at the
      buccal aspect, characterize the healing extraction socket. These result in
      narrowing and shortening of the alveolar ridge, which compromise esthetics and
      complicate restoration. Alveolar ridge augmentation has been proposed to
      facilitate future site restoration by minimizing ridge resorption. Therefore, the
      purpose of this study was to compare extraction socket healing and alveolar ridge
      alteration after socket augmentation using bone allograft covered with an
      acellular dermal matrix (ADM) or polytetrafluoroethylene (PTFE) membrane.
      METHODS: Twenty non-smoking healthy subjects were selected. Each subject required
      maxillary premolar, canine, or central incisor tooth extraction. The extraction
      sites were debrided and grafted with a mineralized bone allograft that was
      covered with an ADM or PTFE membrane. Postoperative appointments were scheduled
      at 2, 4, and 8 weeks. After 16 weeks of healing, final measurements were
      performed, and trephine core biopsies were obtained for histomorphometric
      analysis. Implants were placed immediately after biopsy harvesting. RESULTS:
      Eighteen subjects completed the study. All sites healed without adverse events
      and allowed for implant placement. PTFE membranes exfoliated prematurely, with an
      average retention time of 16.6 days, whereas the ADM membranes appeared to be
      incorporated into the tissues. Buccal plate thickness loss was 0.44 and 0.3 mm,
      with a vertical loss of 1.1 and 0.25 mm, for ADM and PTFE, respectively. Bone
      quality assessment indicated D3 to be the most prevalent (61%). Histomorphometric
      analysis revealed 41.81% versus 47.36% bone, 58.19% versus 52.64% marrow/fibrous
      tissue, and 13.93% versus 14.73% particulate graft remaining for ADM and PTFE,
      respectively. No statistical difference was found between the two treatment
      groups for any of the parameters. CONCLUSION: All sites evaluated showed minimal
      ridge alterations, with no statistical difference between the two treatment
      modalities with respect to bone composition and horizontal and vertical bone
      loss, indicating that both membranes are suitable for alveolar ridge
      augmentation.

PMID- 19405832
TI  - Periodontal therapy reduces plasma levels of interleukin-6, C-reactive protein,
      and fibrinogen in patients with severe periodontitis and refractory arterial
      hypertension.
AB  - BACKGROUND: Recent epidemiologic studies suggest that inflammation is the link
      between periodontal diseases and cardiovascular complications. This study aimed
      to evaluate the effects of non-surgical periodontal treatment on plasma levels of
      inflammatory markers (interleukin [IL]-6, C-reactive protein [CRP], and
      fibrinogen) in patients with severe periodontitis and refractory arterial
      hypertension. METHODS: Twenty-two patients were examined and randomly divided
      into two groups. The test group was composed of 11 patients (mean age, 48.9 +/-
      3.9 years) who received periodontal treatment, whereas the control group had 11
      patients (mean age, 49.7 +/- 6.0 years) whose treatment was delayed for 3 months.
      Demographic and clinical periodontal data were collected, and blood tests were
      performed to measure the levels of IL-6, CRP, and fibrinogen at baseline and 3
      months later. RESULTS: The clinical results showed that the mean percentages of
      sites with bleeding on probing, probing depth (PD) 4 to 5 mm, PD > or =6 mm,
      clinical attachment loss (CAL) 4 to 5 mm, and CAL > or =6 mm were significantly
      reduced in the test group 3 months after periodontal treatment. There were no
      significant differences between the data at baseline and 3 months in the control
      group. Periodontal treatment significantly reduced the blood levels of
      fibrinogen, CRP, and IL-6 in the test group. CONCLUSION: Non-surgical periodontal
      therapy was effective in improving periodontal clinical data and in reducing the
      plasma levels of IL-6, CRP, and fibrinogen in hypertensive patients with severe
      periodontitis.

PMID- 19405833
TI  - Cytokine gene polymorphisms associated with rheumatoid arthritis and
      periodontitis in Japanese adults.
AB  - BACKGROUND: Cytokines play a major role in the pathogenesis of rheumatoid
      arthritis (RA) and periodontitis. Both diseases were previously shown to be
      partly influenced by cytokine gene polymorphisms. Therefore, we evaluated whether
      the distributions of the cytokine genotypes were unique to subjects with both
      diseases. METHODS: The study subjects consisted of Japanese adults with RA (RA
      group; n = 153), periodontitis only (P group; n = 117), and healthy individuals
      (H group; n = 108). Clinical periodontal condition was defined by measurements of
      probing depth, clinical attachment level, and bleeding on probing. Genomic DNA
      was isolated from peripheral blood and analyzed for the determination of 16 gene
      polymorphisms encoding interleukin (IL)-1, -2, -4, -6, and -10, tumor necrosis
      factor-alpha, and transforming growth factor-beta 1. RESULTS: The frequency of
      patients with RA who exhibited periodontitis was 89.5% (RA + P group; n = 137).
      No significant differences were observed in any of the frequencies of cytokine
      genotypes and alleles among the subject groups. After adjustment for age, gender,
      and smoking status, multiple logistic regression analysis revealed a significant
      difference in the distribution of IL-1B +3954 genotypes between RA + P and P
      groups (P = 0.006) and between RA + P and H groups (P = 0.008). CONCLUSION:
      Japanese individuals with RA and periodontitis may exhibit different
      distributions of IL-1B +3954 genotypes than healthy controls and subjects with
      periodontitis only.

PMID- 19405834
TI  - Decreased interleukin-2 responses to Fusobacterium nucleatum and Porphyromonas
      gingivalis in generalized aggressive periodontitis.
AB  - BACKGROUND: Compromised T-cell responses to periodontal pathogens may contribute
      to the pathogenesis of generalized aggressive periodontitis (GAgP). In this
      study, we attempted to characterize T-helper cell (Th1, Th2, and Th17) responses
      in patients with GAgP and healthy controls upon stimulation with disease-relevant
      pathogens. METHODS: Mononuclear cells (MNCs) from 10 white patients with GAgP and
      10 white controls were stimulated with Porphyromonas gingivalis American Type
      Culture Collection (ATCC) 33277 (Pg), Prevotella intermedia ATCC 25611,
      Fusobacterium nucleatum ATCC 49256 (Fn), and similar bacteria isolated from the
      participants' inherent oral flora. Tetanus toxoid (TT) was used as control
      antigen. The resulting production of interferon-gamma (IFN-gamma) and interleukin
      (IL)-2, -4, -5 and -17 and the induced proliferation of CD4+ T cells were
      measured. RESULTS: MNCs from patients with GAgP exhibited decreased IL-2
      responses to Pg and Fn. No difference was observed between patients with GAgP and
      controls with regard to CD4+ T-cell proliferation or the production of IFN-gamma
      and IL-4, -5, and -17, irrespective of whether type strains or bacteria isolated
      from the participants' oral cavity were used for stimulation. Moreover, similar
      proliferative and cytokine responses to TT were observed. Notably, smoking
      patients with GAgP exhibited significantly lower IFN-gamma responses to the
      bacteria and to TT than non-smoking patients or controls. CONCLUSIONS: The
      decreased IL-2 responses of patients with GAgP to Pg and Fn combined with
      adequate IL-2 responses to TT suggest an impaired antigen-specific T-cell
      reactivity with periodontal pathogens in GAgP. The decreased IFN-gamma responses
      of smokers within the patient group suggest that smoking may aggravate this
      impairment.

PMID- 19405835
TI  - Potential of bioactive glass particles of different size ranges to affect bone
      formation in interproximal periodontal defects in dogs.
AB  - BACKGROUND: The aim of this study was to compare the potential of bioactive glass
      particles of different size ranges to affect bone formation in periodontal
      defects, using the guided tissue regeneration model in dogs. METHODS: In six
      dogs, 2-wall intrabony periodontal defects were surgically created and chronified
      on the mesial surfaces of mandibular third premolars and first molars
      bilaterally. After 1 month, each defect was randomly assigned to treatment with
      bioabsorbable membrane in association with bioactive glass with particle sizes
      between 300 and 355 microm (group 1) or between 90 and 710 microm (group 2),
      membrane alone (group 3), or negative control (group 4). The dogs were sacrificed
      12 weeks after surgeries, and histomorphometric measurements were made of the
      areas of newly formed bone, new mineralized bone, and bioactive glass particle
      remnants. RESULTS: With regard to the area of bioactive glass particle remnants,
      there was a statistically significant difference between groups 1 and 2, favoring
      group 1. There were greater areas of mineralized bone in groups 1 and 2 compared
      to groups 3 and 4 (P <0.05). CONCLUSION: The bioactive glass particles of small
      size range underwent faster resorption and substitution by new bone than the
      larger particles, and the use of bioactive glass particles favored the formation
      of mineralized bone.

PMID- 19405836
TI  - Periodontal biotype influence on the volume maintenance of onlay grafts.
AB  - BACKGROUND: Autogenous osseous transplants have advantages, including the
      maintenance of bone density and high concentrations of growth factors. Little is
      known about the potential long-term influence of periodontal biotype on the
      volume maintenance of block grafts. METHODS: Forty patients who received
      autogenous block transplants prior to implant placement were included in the
      study. Digital photographs and periapical radiographs were taken after
      restoration. Clinical parameters, including bleeding on probing, mobility,
      suppuration, mucosal recession, and buccal tissue transparency, were recorded at
      yearly intervals. A computerized tomography (CT) scan was taken at an average of
      42 months (n = 20) postaugmentation. RESULTS: The clinical examination revealed
      no implant transparency, mucosal recession, mobility, bleeding on probing, or
      suppuration (n = 40) at 48 months. CT scans showed varying thicknesses (0.5 to 4
      mm) of buccal cortical bone around the implants. The increased width at the
      recipient site postgraft was 7.6 mm, maintaining, on average, 98% of the
      augmented width. The buccal osseous thickness at the implant sites averaged 2.0
      +/- 0.8 mm compared to 0.7 +/- 0.5 mm for the adjacent teeth (95% confidence
      interval: 0.85 to 1.65 mm; P <0.0001). Even when adjacent teeth had a thin
      biotype, the transplanted sites maintained statistically significant thicker
      buccal cortical plate at all sites (P <0.0001). CONCLUSIONS: Grafted site
      phenotype did not seem to be influenced by the adjacent teeth biotype. Autogenous
      osseous transplants can predictably reconstruct function and esthetics and seemed
      to maintain stable bone volume around implants at an average of 3.5 years.

PMID- 19405837
TI  - Comparative immunohistochemical study of the distribution of fibronectin in
      healthy and diseased root surfaces.
AB  - BACKGROUND: Periodontal disease is an inflammatory process which may result in
      damage to and/or loss of tooth-supporting tissues, including bone, cementum, and
      periodontal ligament. Significant evidence supports a strong correlation between
      periodontitis and diseased or altered cementum. The aim of this study was to
      investigate the presence and distribution of fibronectin in normal human cementum
      and to determine whether its distribution is altered in periodontitis. METHODS:
      Five healthy and 10 periodontally affected teeth were collected. Following
      fixation and demineralization, specimens were embedded in paraffin, sectioned,
      and exposed to antibodies against fibronectin. Stained sections were assessed
      using light microscopy. RESULTS: The distribution of fibronectin, in the form of
      fibrils, in normal cementum was uniform in the whole cementum mass. In recession
      cementum, fibronectin appeared to lose its fibrillar morphology or to be
      completely amorphous on the whole cementum mass. Fibronectin showed variation in
      its distribution and fibrillar structure in pocket cementum; its absence from the
      cementum surface is characteristic. In the cementum apical to the pocket,
      fibronectin showed normal fibril structures, similar to normal cementum.
      CONCLUSIONS: Changes in cementum due to periodontitis include changes in the
      distribution and morphology of fibronectin. These changes may influence the
      ability for regeneration and connective tissue attachment onto periodontally
      affected root surfaces.

PMID- 19405839
TI  - The constitutive activation of extracellular signal-regulated kinase 1 and 2 in
      periodontal ligament nerve fibers.
AB  - BACKGROUND: The extracellular signal-regulated kinases 1 and 2 (ERK1/2) have been
      implicated in the inflammation-dependent sensitization of nociceptors. Because
      the periodontal ligament (PDL) contains numerous nociceptors and mechanoceptors,
      phosphorylation of ERK1/2 was investigated in nerve fibers of the PDL to
      elucidate the role of constitutive local activation of ERK1/2 in peripheral
      sensitization. METHODS: Decalcified free-floating sections of rat molars with PDL
      were incubated using total (t)-ERK1/2 and phosphorylated (p)-ERK1/2 antibodies.
      For identification of nerve fibers in the PDL, double staining was performed
      using protein gene product 9.5 (PGP 9.5) with p-ERK1/2. To test whether p-ERK1/2
      activated in sensory and mechanoreceptive terminals, double incubations were
      performed using p-ERK1/2 with calcitonin gene-related peptide (CGRP) and with
      calretinin. Labeled nerve fibers were quantified by the point-counting method.
      RESULTS: In cervical, midroot, and apical zones of the PDL, t-ERK1/2- and p
      ERK1/2-labeled nerve fibers were found in close association with blood vessels.
      The p-ERK1/2-labeled free nerve fibers were often detected in cervical and apical
      areas of the PDL. In nerve fibers of the PDL, p-ERK1/2 was colocalized with PGP
      9.5, CGRP, and calretinin. CONCLUSIONS: The perivascular distribution of t-ERK1/2
      and p-ERK1/2 in nerve fibers in the PDL is compatible with a role for the
      constitutive activation of ERK1/2 in the neural regulation of blood vessels in
      the PDL. The colocalizations of p-ERK1/2 with CGRP and calretinin indicate that
      ERK1/2 is constitutively activated in a subpopulation of sensory and
      mechanoreceptive nerve terminals in the PDL.

PMID- 19405840
TI  - Removal of an amalgam tattoo using a subepithelial connective tissue graft and
      laser deepithelialization.
AB  - BACKGROUND: A 56-year-old female presented for periodontal treatment with a large
      amalgam tattoo located in alveolar mucosa on the facial aspect of her maxillary
      central incisors. The lesion had been present for 42 years since having
      endodontic surgery at teeth #8 and #9 after a traumatic childhood incident.
      METHODS: A two-stage surgical approach was used to eliminate the lesion,
      beginning with a subepithelial connective tissue graft to increase tissue
      thickness subjacent to the amalgam tattoo. After 6 weeks of healing, the
      overlying pigmented tissue was removed using laser surgery to expose the
      underlying grafted connective tissue. RESULTS: After 2 months of healing
      following laser surgery, the amalgam pigmentation was completely removed, with
      good color match and an increased width of keratinized tissue at the surgical
      site. CONCLUSION: A relatively large amalgam tattoo in the esthetic zone can be
      adequately removed by a two-stage procedure using grafted palatal connective
      tissue and laser deepithelialization.

PMID- 19405838
TI  - Expression profile of human gingival fibroblasts induced by interleukin-1beta
      reveals central role of nuclear factor-kappa B in stabilizing human gingival
      fibroblasts during inflammation.
AB  - BACKGROUND: Interleukin (IL)-1beta is a key cytokine in the pathogenesis of
      periodontitis, and it induces inflammatory mediators in periodontal diseases. We
      developed immortalized human gingival fibroblasts (HGFs), investigated the
      effects of IL-1beta on the gene expression using expression arrays containing
      approximately 40,000 genes, and tested the role of nuclear factor-kappa B (NF
      kappaB) in maintaining an activated HGF population. METHODS: Total RNA was
      isolated from IL-1beta-induced and mock-induced control cells. Gene expression
      analyses were performed using expression arrays and confirmed by quantitative
      real-time polymerase chain reaction. Western blot analysis to show inhibitor of
      kappa B-alpha (IkappaBalpha) phosphorylation and immunostaining of cells for NF
      kappaB nuclear translocation were performed. Apoptosis was confirmed by assay of
      poly ADP-ribose polymerase (PARP) cleavage. RESULTS: A total of 382 probe sets
      corresponding to 254 genes were differentially expressed in IL-1beta-induced
      cells (P <0.001). A total of 215 genes were upregulated, and 39 genes were
      downregulated. Most notable NF-kappaB pathway members (NFkappaB1, NFkappaB2,
      IkappaBalpha, IkappaBepsilon, IkappaBzeta, REL, RELB, and TA-NFKBH) were
      upregulated. IkappaBalpha was phosphorylated, and NF-kappaB accumulated in the
      nucleus. An IL-1beta-induced set of 27 genes was downregulated by an NF-kappaB
      inhibitor, leading to a decreased number of viable cells and suggesting an
      antiapoptotic role for NF-kappaB. CONCLUSIONS: IL-1beta leads to a large number
      of significant expression changes consistent with a pathologic role in
      periodontitis, including enhancement of inflammatory cytokines, chemokines,
      transcription factors, matrix metalloproteinases, adhesion molecules, and
      especially NF-kappaB-dependent antiapoptotic genes. NF-kappaB activation blocks
      apoptosis, thereby stabilizing the HGF population in inflammation.

PMID- 19405841
TI  - Symphysis revisited: clinical and histologic evaluation of newly formed bone and
      reharvesting potential of previously used symphysial donor sites for onlay bone
      grafting.
AB  - BACKGROUND: This article reports on the reharvesting potential of newly formed
      bone in previously used symphysial donor sites. METHODS: This study included five
      patients who were scheduled for sequential onlay bone augmentations prior to
      dental implant placement using the symphysis area as a donor site. At 5 months
      after bone augmentation, computed tomography scans of donor sites revealed
      healing from the first surgery. Because additional bone augmentation was
      required, the same sites were revisited for bone harvesting. Reharvesting was
      performed 5 months after the first harvesting. A small portion of the harvested
      bone from two patients was evaluated histologically. RESULTS: Five months
      postharvesting, clinical observation of the donor sites resembled newly formed
      bone as a conglomerate of bovine bone particles. In the five patients, bone
      continuity was observed between new bone at the donor defect sites and
      surrounding bone. Additional blocks were reharvested from the same sites and
      successfully grafted to recipient sites. Dental implants were inserted 5 months
      after the second augmentation, which healed uneventfully. Histologically, bovine
      bone particles were surrounded by woven bone, with areas of mature bone with well
      organized osteons. CONCLUSIONS: Remodeling of a symphysial donor area enabled
      reuse of the site for additional harvesting. Intraoral bone sources could serve
      as a long-lasting renewable source of high-quality bone.

PMID- 19405857
TI  - The application of low-level laser therapy after cesarean section does not
      compromise blood prolactin levels and lactation status.
AB  - OBJECTIVE: This study evaluates the systemic effect of low-level laser therapy
      (LLLT) on blood prolactin levels and lactation status when it is used to hasten
      surgical wound healing in women having undergone a cesarean section. BACKGROUND
      DATA: LLLT has been used in parturient patients for postpartum mastitis and
      nipple soreness. However, previous studies have revealed hormonal and
      physiological effects of LLLT on the lactation status. MATERIALS AND METHODS:
      Twenty healthy women scheduled for cesarean section were randomly divided into
      two groups: an LLLT group and a control group. LLLT was delivered as follows: (1)
      irradiation with 980 nm (100 mW, 3.3 J/cm(2), total energy 60 J), and 650 nm (30
      mW, 1.5 J/cm(2), total energy 27 J) to the incision line, and (2) intravenous
      laser irradiation at 2.5 mW and 650 nm for 15 min on three consecutive
      postoperative days. Except for LLLT, all the therapeutic conditions in both
      groups were identical. Blood prolactin levels were measured in the groups on the
      third postoperative day, and tissue samples were taken from the wound margins for
      histological evaluation on the 10th postoperative day. RESULTS: Although there
      was a difference between blood prolactin levels in the two groups, the difference
      was not statistically significant (p = 0.205). However, there was a statistically
      significant difference in the mean lymphocyte counts and number of vessel lumina,
      with higher numbers seen in the LLLT group. CONCLUSION: LLLT after cesarean
      section has no serious deleterious effects on lactation, and it helps to modulate
      metabolic processes and thus promotes wound healing post-surgery.

PMID- 19405858
TI  - Efficacy of interferential low-level laser therapy using two independent sources
      in the treatment of knee pain.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of an
      interferential pattern generated by two identical and independent lasers in the
      relief of knee pain. BACKGROUND DATA: Low-level laser therapy (LLLT) is generally
      applied by a single probe. MATERIALS AND METHODS: A double-blind controlled
      clinical trial was performed on 152 patients with knee pain who were randomly
      assigned into two different groups. Group I patients (n = 76) received
      interferential laser therapy generated by two identical laser probes located
      opposite each other on the knee joint. Group II patients (n = 76) received one
      live probe in conventional laser therapy and one dummy probe. The device used in
      both groups was an AlGaAs laser (wavelength 810 nm, power 100 mW, in continuous
      mode). Fifteen laser sessions were applied transcutaneously on 5 knee points (6
      J/point) per session. In addition, patients in both groups received a quadriceps
      strength program based on isometric exercises. A visual analogue scale (VAS) was
      used for pain evaluation in different situations, such as in standing, in knee
      flexion/extension, and when going up and down stairs. VAS pain scores were
      evaluated before, in the middle of, and after treatment. RESULTS: ANOVA results
      showed no significant differences between groups for all VAS scores or in the
      interaction with the sessions (p > 0.05). The VAS score results showed a
      statistically significant pain reduction throughout all sessions (p = 0.000).
      CONCLUSIONS: Interferential laser therapy is safe and effective in reducing knee
      pain. However, the results of the study indicate that it is not superior to the
      use of a single conventional laser.

PMID- 19405848
TI  - Syndromes of telomere shortening.
AB  - Telomeres and telomerase were initially discovered in pursuit of questions about
      how the ends of chromosomes are maintained. The implications of these discoveries
      to age-related disease have emerged in recent years with the recognition of a
      group of telomere-mediated syndromes. Telomere-mediated disease was initially
      identified in the context of dyskeratosis congenita, a rare syndrome of premature
      aging. More recently, mutations in telomerase components were identified in
      adults with idiopathic pulmonary fibrosis. These findings have revealed that the
      spectrum of telomere-mediated disease is broad and includes clinical
      presentations in both children and adults. We have previously proposed that these
      disorders be collectively considered as syndromes of telomere shortening. Here,
      the spectrum of these disorders and the unique telomere genetics that underlies
      them are reviewed. I also propose broader clinical criteria for defining telomere
      mediated syndromes outside of dyskeratosis congenita, with the goal of
      facilitating their diagnosis and highlighting their pathophysiology.

PMID- 19405859
TI  - Blue laser irradiation enhances extracellular calcification of primary
      mesenchymal stem cells.
AB  - BACKGROUND DATA AND OBJECTIVE: Mesenchymal stem cells (MSCs) are multipotent
      cells present in adult bone marrow that replicate as undifferentiated cells and
      can differentiate to lineages of mesenchymal tissues. Homeostatic control of bone
      remodeling maintains bone mass by ensuring that bone resorption and bone
      formation occur sequentially and in a balanced manner. As most homeostatic
      functions occur in a circadian manner, a circadian clock could control bone mass.
      Here we show that laser irradiation can direct the extracellular calcification of
      mouse MSCs by altering the intracellular localization of the circadian rhythm
      protein cryptochrome 1 (CRY1). MATERIALS AND METHODS: MSCs were irradiated with a
      blue laser (wavelength 405 nm) for 180 sec via a fiber attached to the bottom of
      the culture dish. After laser irradiation, the MSCs were incubated in osteogenic
      differentiation medium for 5 d. After laser irradiation, circadian rhythm protein
      CRY1 was immunostained and histochemical staining for extracellular calcification
      was observed. RESULTS: Laser irradiation promoted extracellular calcification of
      MSCs, induced the translocation of CRY1 protein from the cytoplasm to the
      nucleus, and decreased CRY1 mRNA levels quantified by real-time PCR. Since the
      timing of nuclear accumulation of clock proteins constitutes an important step in
      the transcription-translation feedback loop driving the circadian core
      oscillator, laser irradiation could provide a simple and effective technology for
      clock protein localization and turnover. Our results also indicate that CRY1 is a
      master regulator of circadian rhythm that regulates the extracellular
      calcification of MSCs. CONCLUSION: Laser irradiation could provide a simple and
      effective means of controlling the fate of MSCs as a therapeutic strategy, and
      act as a "molecular switch" of regulatory proteins by suppressing CRY
      transcription. Furthermore, this model system may be useful for exploring the
      cross-talk between circadian rhythm and cell function.

PMID- 19405860
TI  - Recall of three heart disease risk factor diagnoses among low-income women.
AB  - BACKGROUND: Success of interventions targeting heart disease risk factors depends
      largely on whether patients understand their risk factors, as awareness and
      acceptance are necessary steps in controlling and managing these conditions. The
      goal of this analysis was to assess whether women with identified heart disease
      risk factors are able to recall their diagnoses 1 year later. METHODS: The
      WISEWOMAN program provides heart disease screening and intervention services to
      low-income underinsured and uninsured women. The study used 2000-2005 data for
      WISEWOMAN participants with newly identified high blood pressure, high
      cholesterol, or diabetes to assess their likelihood of reporting never having
      been told of their conditions 1 year later. RESULTS: Among women with high blood
      pressure at baseline, 66% (n = 1140) reported never having been told they have
      this condition 1 year later. Black women were less likely to report never being
      told (OR 0.62, p < 0.01) than white women. Women older than 60 were more likely
      to report never being told (OR = 1.62, p < 0.01) than women younger than 50.
      Among women with high cholesterol at baseline, 46% (n = 1312) reported never
      being told 1 year later. Less educated women were more likely to report never
      being told (OR 2.29, p < 0.01) than high school graduates. Among women with high
      glucose at baseline, 54% (n = 123) reported never being told 1 year later.
      CONCLUSIONS: A provider-patient communication gap or inability of low-income
      patients to retain health information hampers public health efforts to encourage
      individuals with heart disease risk factors to make the behavior changes
      necessary to reduce these risks.

PMID- 19405861
TI  - Sex differences in the incidence of hemorrhagic and ischemic stroke among
      diabetics in Taiwan.
AB  - BACKGROUND: Diabetes mellitus is an important risk factor for stroke, but whether
      there is differential gender-specific risk has not been fully elucidated. We
      aimed to explore the impact of gender on incidence and relative risks of
      hemorrhagic and ischemic stroke among the diabetic population in Taiwan. METHODS:
      In this study, 500,868 diabetic patients and 500,248 age matched and-sex-matched
      nondiabetic individuals were linked to inpatient claims (1997-2002) to identify
      hospitalizations for nontraumatic hemorrhagic and ischemic stroke. Incidence
      density was calculated with the Poisson assumption, and Kaplan-Meier analysis was
      used to assess the cumulative incidence over a 6-year follow-up period. We also
      evaluated the relative hazards of stroke in relation to diabetes with the Cox
      proportional hazard model, adjusted with demographics and geographic regions.
      RESULTS: The incidence of hemorrhagic stroke in diabetic women was less than that
      in diabetic men except in those aged > or =85, but the difference between male
      and female diabetic patients was less pronounced with ischemic stroke. The hazard
      ratios (HRs) of hemorrhagic and ischemic stroke among diabetic women were
      increased by a magnitude of 1.2 and 1.32, respectively, which were significantly
      higher than those of diabetic men. Further age-stratified analysis indicated that
      young and middle-aged diabetic women tended to have higher HRs and that diabetic
      women aged <35 suffered from particularly high HRs (HR 7.69, 95% confidence
      interval [CI] 1.81-32.75 for hemorrhagic stroke, and HR = 8.46, 95% CI 4.28-16.75
      for ischemic stroke). CONCLUSIONS: There was a significant gender-diabetes
      interactive effect on the incidence of hemorrhagic and ischemic stroke.
      Additionally, young Taiwanese diabetic patients were most vulnerable to an
      increased relative risk of hemorrhagic and ischemic stroke. Comprehensive
      diabetic care with stroke prevention measures should be emphasized in young
      diabetic people in order to prevent premature disability.

PMID- 19405847
TI  - Unraveling a multifactorial late-onset disease: from genetic susceptibility to
      disease mechanisms for age-related macular degeneration.
AB  - Aging-associated neurodegenerative diseases significantly influence the quality
      of life of affected individuals. Genetic approaches, combined with genomic
      technology, have provided powerful insights into common late-onset diseases, such
      as age-related macular degeneration (AMD). Here, we discuss current findings on
      the genetics of AMD to highlight areas of rapid progress and new challenges. We
      also attempt to integrate available genetic and biochemical data with cellular
      pathways involved in aging to formulate an integrated model of AMD pathogenesis.

PMID- 19405863
TI  - In vivo and in vitro efficacy of amodiaquine against Plasmodium falciparum in an
      area of continued use of 4-aminoquinolines in East Africa.
AB  - In light of reports of increasing resistance of parasites to amodiaquine in
      African countries in which Plasmodium falciparum is endemic as well as the
      paucity of recent in vitro sensitivity data, we assessed the in vivo and in vitro
      sensitivity to amodiaquine of P. falciparum isolates from 128 pediatric
      outpatients (0.5-10 years old) in Pingilikani, Kilifi District, Kenya, who were
      treated with amodiaquine (10 mg/kg/day for 3 days). The polymerase chain reaction
      corrected parasitological cure rate on day 28 (by Kaplan-Meier analysis) was 82%
      (95% confidence interval [CI], 74%-88%). Twenty-six percent (17/66) of tested
      pretreatment P. falciparum field isolates had 50% in vitro growth inhibition at
      concentrations of N-desethyl-amodiaquine (DEAQ)-the major biologically active
      metabolite of amodiaquine-above the proposed resistance threshold of 60 nmol/L,
      but baseline median DEAQ 50% inhibitory concentration values were not associated
      with subsequent risk of asexual parasite recrudescence (29 nmol/L [95% CI, 23-170
      nmol/L] and 34 nmol/L [95% CI, 30-46 nmol/L] for patients with and those without
      recrudescences, respectively). The median absolute neutrophil count dropped by
      1.3 X 10(3) cells/microL (95% CI, -1.7 X 10(3) to -0.7 X 10(3) cells/microL)
      between days 0 and 28. The high prevalence of in vitro and in vivo resistance
      precludes the use of amodiaquine on its own as second-line treatment. These
      findings also suggest that the value of amodiaquine combinations as first- or
      second-line treatment in areas with similar patterns of 4-aminoquinoline
      resistance should be reassessed.

PMID- 19405862
TI  - Quality of life and self-esteem of long-term survivors of invasive and
      noninvasive cervical cancer.
AB  - OBJECTIVE: We compared long-term survivors of invasive and noninvasive cervical
      cancer (1) to determine if there are differences in the quality of life (QOL) and
      (2) to assess the association between self-esteem and QOL. METHODS: A sample of
      cervical cancer survivors diagnosed with invasive and noninvasive cervical cancer
      during 1995-1996 was drawn from the metropolitan Detroit Surveillance,
      Epidemiology, and End Results (SEER) cancer registry. There were 145
      participating survivors, 42 with invasive and 103 with noninvasive cervical
      cancer. Data were collected using a structured interview, conducted primarily
      over the telephone. The outcome measures were the QOL (measured by the Medical
      Outcomes Study Short Form-36 [SF-36]) summary scales, the Physical Component
      Summary (PCS) score and the Mental Component Summary (MCS) score. Differences in
      MCS and PCS between women with invasive and noninvasive cancer were determined
      using analysis of covariance (ANCOVA). Multivariate analysis was performed to
      determine the association between self-esteem and MCS and PCS. RESULTS: There
      were no differences in either PCS or MCS scores between long-term survivors of
      invasive and noninvasive cervical cancer. Self-esteem was associated with MCS but
      not with PCS in women with invasive cancer as well as in women with noninvasive
      cancer. CONCLUSIONS: The distinctive association of self-esteem with MCS but not
      PCS indicates that interventions for supporting and improving self-esteem may be
      more effective by promoting psychological well-being rather than physical well
      being. Moreover, women with noninvasive cervical cancer, a group often neglected
      in cervical cancer studies, should also be targeted for these interventions.

PMID- 19405864
TI  - Identification of MICA as a susceptibility gene for pulmonary Mycobacterium avium
      complex infection.
AB  - Host genetic susceptibility to adult pulmonary Mycobacterium avium complex
      disease remains unknown. To identify genetic loci for the disease, we prepared 3
      sets of pooled DNA samples from 300 patients and 300 sex-matched control subjects
      and genotyped 19,651 microsatellite markers in a case-control manner. D6S0009i
      located in the MICA (major histocompatibility complex class I chain-related A)
      gene, which encodes a ligand of the NKG2D receptor-had the lowest P value in
      pooled and individual DNA typing. The A6 allele of the microsatellite was
      significantly associated with female patients (P <. 001), whereas the classical
      HLA-B and HLA-DRB1 alleles did not show significant association. Functional
      analysis of allelic expression imbalance revealed that A6-derived messenger RNA
      was more highly expressed than non-A6-derived messenger RNA in human bronchial
      epithelial cells. MICA was expressed in bronchiolar epithelium, alveolar
      macrophages, and granulomatous lesions. These findings suggest that MICA might be
      one of the immune molecules affecting the pathogenesis of the disease.

PMID- 19405865
TI  - Influence of loop electrosurgical excision procedure on subsequent acquisition of
      new human papillomavirus infections.
AB  - BACKGROUND: The impact of loop electrosurgical excision procedure (LEEP)
      treatment for cervical precancerous lesions on subsequent acquisition of new
      human papillomavirus (HPV) infections is not well described. METHODS: The
      acquisition of new HPV infections was compared in HPV-positive women who
      underwent colposcopy and were treated by LEEP (n = 195) and those who were
      untreated (n = 1625) at entry into a 2-year study. Cumulative incidence rate
      ratios (IRRs) for treated versus untreated women at 6- and 24-months of follow
      up, with 95% confidence intervals (CIs), were calculated for infection by
      individual HPV genotypes, any HPV genotypes, any carcinogenic HPV genotypes, any
      noncarcinogenic HPV genotypes, and phylogenetic groups of HPV genotypes. RESULTS:
      Treated women were 29% less likely than untreated women to have carcinogenic HPV
      genotypes detected at 6-month follow-up visits (IRR, 0.71; 95% CI, 0.50-1.00) and
      were 18% less likely to have these genotypes detected at 24-month follow-up
      visits (IRR, 0.82; 95% CI, 0.68-1.01). Treated women were 56% less likely to have
      HPV genotypes of the alpha9 phylogenetic species (which includes HPV-16) detected
      at 6-month follow-up visits (IRR, 0.44; 95% CI, 0.23-0.85) and were 40% less
      likely to have these genotype detected at 24-month follow-up visits (IRR, 0.60;
      95% CI, 0.42-0.85). CONCLUSION: LEEP may reduce the acquisition of certain
      carcinogenic HPV genotypes related to HPV-16.

PMID- 19405866
TI  - Sequelae of World War II: an outbreak of chronic cutaneous nontuberculous
      mycobacterial infection among Satowanese islanders.
AB  - BACKGROUND: After World War II, residents of Satowan (population, 650 persons),
      an outer island in the state of Chuuk, Federated States of Micronesia, noted a
      high prevalence of a chronic, progressive skin disease known locally as "spam."
      METHODS: Island residents who had chronic, progressive verrucous or keloidal
      plaques for >3 months were considered case patients. Tissue specimens were
      obtained for culture, histopathological analysis, mycobacterial polymerase chain
      reaction (PCR), and comparison with the hsp65 gene of Mycobacterium marinum. We
      performed a case-control study involving all cases and randomly selected control
      individuals from the community. RESULTS: A total of 39 case patients were
      identified, with a median age of 26.0 years (range, 8-82 years); 74.4% were male,
      and the mean duration of disease was 12.5 years. A total of 98 control
      individuals were enrolled. Results of all 19 mycobacterial tissue cultures were
      negative, and histopathological analysis of all 9 lesions showed suppurative
      granulomatous inflammation with negative results of mycobacterial and fungal
      stains. In 7 of 9 paraffin-embedded samples, nontuberculous mycobacterial DNA was
      detected by PCR, and 2 sequenced products had 95% and 87% identity to M. marinum.
      All case patients were taro farmers (odds ratio, undefined; P < .01), and among
      taro farmers, when the analysis was controlled for sex, contact with water-filled
      World War II-era bomb craters was associated with infection (odds ratio, 8.2; P <
      .01). CONCLUSIONS: "Spam disease" is a chronic, progressive skin disease of high
      prevalence on Satowan and is associated with taro farming and contact with World
      War II-era bomb craters. Histopathological and PCR data demonstrate a
      nontuberculous mycobacterial infection as the cause.

PMID- 19405868
TI  - The relationship between obesity and fecundity.
AB  - OBJECTIVE: Obesity is an important factor that might reduce fecundity. In order
      to determine the underlying physiological mechanisms and risk factors, the
      obesity-fecundity association is investigated in relation to parity, menstrual
      cycle regularity, smoking habits, and age. METHODS: This was a retrospective
      cohort study of 22,840 women who gave birth between January 2006 and January 2007
      in the Dr Zekai Tahir Burak Women's Health Research and Education Hospital. Age,
      parity, prepregnancy body mass index (BMI) values, time to pregnancy data related
      to smoking, and reproductive, medical, and gynecological history were obtained
      from the medical records. RESULTS: Fecundity was reduced for overweight and obese
      women compared with optimal weight women, and this reduction was more evident for
      obese primiparous women. Fecundity remained reduced for overweight and obese
      women with normal menstrual cycles. Obese and overweight women were found to
      smoke significantly more than the optimal weight group. CONCLUSIONS: Obesity was
      found to be associated with reduced fecundity for all weight-adjusted groups of
      women and persisted for women with regular cycles. Weight loss should be
      encouraged initially during the treatment of infertile overweight and obese
      women.

PMID- 19405867
TI  - Neurologic manifestations of paradoxical tuberculosis-associated immune
      reconstitution inflammatory syndrome: a case series.
AB  - BACKGROUND: Paradoxical neurologic tuberculosis-associated immune reconstitution
      inflammatory syndrome (TB-IRIS) is a potentially life-threatening condition that
      occurs within 3 months after starting combination antiretroviral therapy (ART).
      The reports in the published literature are anecdotal, and the prevalence and
      outcomes of neurologic TB-IRIS are unknown. METHODS: We prospectively assessed
      patients with suspected TB-IRIS from June 2005 through October 2007 at our
      hospital in Cape Town, South Africa. We defined paradoxical TB-IRIS and
      paradoxical neurologic TB-IRIS with use of consensus clinical case definitions.
      We collected data on tuberculosis diagnosis, ART, details of TB-IRIS diagnosis,
      other opportunistic infections, corticosteroid use, and outcome. RESULTS: We
      reviewed 279 patients with suspected TB-IRIS, 54 (19%) of whom had suspected
      neurologic TB-IRIS, and 225 (81%) of whom had suspected non-neurologic TB-IRIS.
      Paradoxical TB-IRIS was diagnosed in 190 patients; 23 (12%) of these 190 patients
      had neurologic TB-IRIS (95% confidence interval, 7%-17%). Eight had meningitis, 7
      had tuberculoma, 5 had both tuberculoma and meningitis, and 3 had
      radiculomyelopathy. Twenty (87%) of the 23 patients with neurologic TB-IRIS
      required hospital admission (median duration, 12 days; interquartile range, 6-24
      days), and 21 (91%) received corticosteroids (median duration, 58 days;
      interquartile range, 29-86 days). Outcomes 6 months after the initial assessment
      for neurologic deterioration were as follows: 16 (70%) of the patients were alive
      (10 of these patients had documented full physical and mental recovery), 3 (13%)
      were dead, and 4 (17%) were lost to follow-up. CONCLUSIONS: Paradoxical
      neurologic TB-IRIS accounts for 12% of paradoxical TB-IRIS cases. Neurologic TB
      IRIS causes considerable short-term morbidity but has reasonable long-term
      outcomes. Further research is needed to devise optimal diagnostic and management
      strategies for patients with tuberculosis who experience neurologic deterioration
      after starting ART.

PMID- 19405869
TI  - Postpartum sacral fracture presenting as lumbar pain.
AB  - Abstract Many woman have low back pain and sacral pain during pregnancy and in
      the postpartum period. The pain is most often caused by mechanical compression of
      the soft tissues and ligaments in the pelvis. It is rare for a sacral fracture to
      cause pain during pregnancy or immediately after birth. Few cases of sacral
      fracture in the postpartum period have been reported to date. Here, we describe
      the imaging features of a sacral fracture associated with radicular symptoms in a
      woman who had just delivered her first child.

PMID- 19405870
TI  - Autoimmune hepatitis in the HIV-infected patient: a therapeutic dilemma.
AB  - Autoimmune hepatitis (AIH) is a progressive, chronic hepatitis that has rarely
      been reported in HIV-infected individuals. Among patients who are candidates for
      hepatitis C virus (HCV) treatment, screening for AIH should be considered,
      because interferon has the potential to cause fulminant hepatic failure in the
      setting of immune-mediated injury. During a 4-year period, we identified four HIV
      infected patients who were referred for evaluation of persistently elevated
      aminotransferases, two of whom were also infected with HCV. Serologic testing and
      the hepatic histologic appearance were consistent with AIH. Although each patient
      initiated treatment with corticosteroids and immunosuppressive agents, all four
      eventually developed life-threatening infectious or adverse metabolic effects
      that resulted in treatment discontinuation. Of note, one HIV/HCV co-infected
      patient was able to initiate HCV treatment with interferon after AIH remission
      was documented. While these cases illustrate that AIH can produce hepatic injury
      in virally infected individuals, we recommend that treatment for AIH in HIV
      infected patients should be individualized after careful consideration of the
      potential risks and likely benefits.

PMID- 19405871
TI  - Semi-automated unidirectional sequence analysis for mutation detection in a
      clinical diagnostic setting.
AB  - BACKGROUND: The past 10 years have seen an improvement in sequence data quality
      due to the introduction of capillary sequencers and new sequencing chemistries.
      In parallel, new software programs for automated mutation detection have been
      developed. We evaluated the sensitivity of semiautomated unidirectional sequence
      analysis for the detection of heterozygous base substitutions using the Mutation
      Surveyor software package. METHODS: Detection rates for heterozygous base
      substitutions in 29 genes by automated and visual inspection were compared.
      Examples of heterozygous bases not detected in one direction during bidirectional
      analysis were also sought through a national survey of United Kingdom (UK)
      genetics laboratories. Sequence quality was assessed in a consecutive cohort of
      50 patients for whom the 39 exons of the ABCC8 gene had been sequenced in one
      direction. RESULTS: A total of 701 different heterozygous base substitutions were
      detected by the software with no false negatives (sensitivity >or=99.57%). Four
      examples of heterozygous bases missed in one direction during bidirectional
      analysis were reported. Two were detected using unidirectional analysis settings,
      and the other two bases had low-quality scores. Of the 1950 amplicons examined,
      97.2% had a quality score >or=30 and an average PHRED-like score >or=50 for the
      defined region of interest, and 98.1% of the 323,650 bases had a PHRED score >40.
      CONCLUSIONS: We found no evidence to support a requirement for bidirectional
      sequencing. Semiautomated analysis of good quality unidirectional sequence data
      has high sensitivity and is suitable for heterozygote mutation scanning in
      clinical diagnostic laboratories. Further work is required to determine minimum
      quality parameters for semiautomated analysis.

PMID- 19405872
TI  - Killer cell immunoglobulin-like receptor genotypes in Behcet's disease patients:
      any role for the 3DP1*001/002 pseudogene?
AB  - AIMS: Genotypic profiles of the natural killer cell immunoglobulin-like receptors
      (KIR) have been reported to vary among different ethnic groups and variable
      clinical entities. This study represents the second report on its distribution
      among patients with Behcet's disease (BD). We studied 43 unrelated Lebanese
      Behcet's patients, had their DNA typed using sequence-specific primer technique
      for the presence of 16 KIR genes and pseudogenes loci, and compared them to the
      general Lebanese population. RESULTS: In addition to sharing common features with
      the general population, the AA genotype was still the most frequent--however,
      with five new KIR profiles identified. There was no statistically significant
      distribution of the different KIR genes between the cases (BD patients) and
      controls (Lebanese population); however, KIR3DP1*001/002 was found to be
      significantly different between the BD patients and the Lebanese population, but
      this significance was lost after correction for all KIR loci. CONCLUSION: The
      results lead to an interesting future research question of whether or not KIR
      genotype is involved in the predisposition to or pathogenesis of BD especially
      that a pseudogene is controversially in question. This is the second report that
      describes the KIR genotypic profile in such an important clinical disease but the
      first to shed a light on the possible role of a pseudogene.

PMID- 19405873
TI  - Genetic testing of stored biological samples: views of 570 U.S. workers.
AB  - AIMS: Storing tissue samples for future genetic testing raises practical and
      ethical issues regarding informed consent and confidentiality. Employed adults'
      views on this are uniquely valuable but have been little studied. METHODS: This
      study surveyed 570 employees at a U.S. defense laboratory and an academic medical
      center regarding their willingness to have tissue stored for future genetic
      testing, interest in receiving results of future testing and being contacted for
      consent for future testing, and acceptability of various tissue-storage options.
      RESULTS: Respondents were somewhat interested in providing samples and
      significantly less interested in providing traceable samples than untraceable
      samples. Workers with concerns about having a genetic illness were more
      interested in providing tissue for future testing. Most participants expressed
      strong desire to be asked before future genotyping and to receive those test
      results. Respondents preferred that tissue samples be stored with their doctor,
      local medical facility, or local research university rather than with their
      employer, a government agency, or an insurance company. CONCLUSIONS: Employed
      adults valued future genetic testing as being important to their well-being and
      strongly preferred reconsenting for future use of stored tissue. These data
      provide a baseline to measure potential changes in workers' attitudes since the
      passage of the U.S. Genetic Information Nondiscrimination Act in 2008.

PMID- 19405874
TI  - Identification of patients at high risk of psychological distress after BRCA1
      genetic testing.
AB  - To predict which women might suffer from abnormally high levels of anxiety and
      depression after receiving a positive genetic BRCA1 test result, series of
      pregenetic testing and postgenetic testing psychological measurements were
      performed. Of 3524 women who returned the psychological test sheets before
      receiving their genetic test result, 111 women were found to carry a BRCA1
      mutation. We found that overall, anxiety does not increase in women who receive a
      positive BRCA1 genetic test result; however, women who experience high levels of
      anxiety before genetic testing continue to experience high levels of anxiety up
      to 1 year posttesting. There were differences in cancer-related distress in
      affected and unaffected women. BRCA1 carriers with a previous diagnosis of cancer
      had significantly higher levels of cancer-related distress at 1 month posttest
      than those without cancer. Our findings suggest that healthcare providers should
      consider including a brief pretest psychological assessment before initiating
      genetic testing for BRCA1 and BRCA2.

PMID- 19405875
TI  - The BRCA1 3'-UTR: 5711+421T/T_5711+1286T/T genotype is a possible breast and
      ovarian cancer risk factor.
AB  - BACKGROUND: A significant proportion of familial and early-onset breast and
      ovarian cancers occur in individuals without coding mutations of BRCA1 and BRCA2.
      AIMS: We identified genetic variation at 3'-untranslated region (UTR) of BRCA1 in
      familial and early-onset breast and ovarian cancer patients both with and without
      BRCA1/2 mutation in the coding regions (BRCA1/2 pos and BRCA1/2 neg), and
      verified the possible cancer risk factor of the specific 3'-UTR variation using
      functional analysis. METHODS: BRCA1 SNP analysis was screened in 46 patients and
      103 unaffected Thais by heteroduplex analysis and DNA sequencing. After chi
      square test for the potential cancer association of the specific 3'-UTR
      genotypes, the functional tests were conducted using several strategies of the
      luciferase gene expression model. RESULTS: We document the existence of two 3'
      UTR polymorphic sites, the 5711+421(G or T) and the 5711+1286(C or T). Frequency
      of homozygous genotype 5711+421T/T_5711+1286T/T (or T/T-T/T) in the group of
      BRCA1/2 neg cancer patients was triple of that seen in unaffected persons and
      showed a significant cancer association (p = 0.007). Functional analysis of these
      polymorphic sites using luciferase experiments showed an obvious significant
      reduction in activity associated with the T allele at both sites. CONCLUSION:
      These results suggest that the inheritance of specific 3'-UTR polymorphisms may
      predispose individuals to early-onset or familial breast or ovarian cancer.

PMID- 19405876
TI  - Species identification through DNA "barcodes".
AB  - Conventional methods for forensic species identification are mainly based on
      immunological procedures, which have limited applications for old and degraded
      specimens. The mitochondrial cytochrome b gene sequence has emerged in forensics
      among molecular methods. Recent investigations in the taxonomic field have
      suggested that a DNA-based identification system may aid the resolution of animal
      diversity and classification using sequence analysis and phylogenetic links.
      Selected gene sequences can be viewed as a genetic "barcode," which is enclosed
      in every cell, and barcoding is a standardized approach for characterizing
      species using short DNA sequences as a diagnostic biomarker for organisms. The
      aim of this study was to evaluate the potential of barcode mitochondrial genes,
      such as the cytochrome c oxidase sub 1 (COI) and the 16S rRNA gene, as a forensic
      tool. We developed a new approach for species testing and identification with a
      singleplex PCR amplification that will be useful not only in criminal casework
      but also in biosecurity, food authentication, investigation against poaching or
      illegal trade of endangered species, and wildlife enforcement. Seven fragments
      ranging from 157 to 541 bp (base pairs) in humans were selected from COI and 16S
      rRNA genes by different redesigned sets of primers suitable for forensic
      purposes. The specificity of each primer pair was evaluated with a single PCR
      reaction on different substrates, and the diversity values were calculated by
      statistical tests to select a set of markers that could be useful in different
      caseworks. A case example of forensic species identification is also presented.

PMID- 19405877
TI  - Primer site polymorphisms: potential implications for bone marrow engraftment
      monitoring.
AB  - Assessment of chimerism after allogeneic bone marrow transplant frequently relies
      on PCR amplification of donor- and recipient-specific polymorphic short tandem
      repeats (STR) with subsequent fluorescent detection of amplicons. In vitro
      amplification of STR loci is often achieved through commercially available,
      multiplex PCR kits. While originally developed for forensic purposes, these kits
      are increasingly being used in clinical laboratories for early detection of graft
      failure and relapse of disease. Despite the obvious benefits of sensitivity,
      accuracy, reproducibility, and ease-of-use of these commercial kits, laboratories
      must understand the technological shortcomings of such assays to avoid
      misinterpretation of patient results. The current case illustrates how primer
      site polymorphisms associated with specific STR alleles can potentially lead to
      erroneous interpretation of engraftment analysis using one of these multiplex STR
      kits.

PMID- 19405878
TI  - Deletion of exons 1a-2 of BRCA1: a rather frequent pathogenic abnormality.
AB  - Women carrying a pathogenic mutation in either BRCA1 or BRCA2 have a major risk
      of developing breast and/or ovarian cancer. The majority of mutations in these
      genes are small point mutations. Since the development of multiplex ligation
      dependent probe amplification, an increasing number of large genomic
      rearrangements have been detected. Here, we describe the characterization of
      pathogenic deletions of exons 1a-2 of BRCA1 in six families using loss of
      heterozygosity, array comparative genomic hybridization, and sequence analyses.
      Two families harbor a 37 kb deletion starting in intron 2 of psi BRCA1,
      encompassing NBR2, and exons 1a-2 of BRCA1, while the other four families have an
      8 kb deletion with breakpoints in intron 2 of NBR2 and intron 2 of BRCA1. This
      observation, together with the previously described families with exon 1a-2
      deletions of BRCA1, demonstrates that this type of deletions is relatively
      frequent in breast/ovarian cancer families.

PMID- 19405879
TI  - Association between the ACTN3 R577X polymorphism and artistic gymnastic
      performance in Italy.
AB  - The ACTN3 (R577X) gene encodes for a structural protein that is exclusively
      expressed in the Z-disc of type II muscle fibers. Homozygosis (577XX) for the
      stop codon in the ACTN3 polymorphism results in alpha-actinin-3 complete
      deficiency. Previous studies have shown low frequencies of the ACTN3 XX genotype
      in elite sprinters compared to the general population. This study tests 35
      Italian elite gymnasts and 53 controls. ACTN3 XX genotype (2.8% vs. 18.8%; p <
      0.04) and X allele (27.1% vs. 43.3%; p < 0.04) frequencies were significantly
      lower in gymnasts compared to controls. The ACTN3 XX genotype was
      underrepresented in female and male gymnasts compared to controls, but was only
      significant for males (male: 0% vs. 16.1%, p < 0.04; female: 5.5% vs. 22.7%, p =
      0.39). These results suggest that alpha-actinin-3 is beneficial to skeletal
      muscle function in generating forceful contractions at high velocity. In
      conclusion, our results associated the ACTN3 R577X polymorphism with male and
      possibly female elite gymnastic performance.

PMID- 19405880
TI  - Executive Board cuts costs to balance 2010 budget.

PMID- 19405882
TI  - What is your diagnosis? Discrete prostatic cysts.

PMID- 19405883
TI  - Filovirus infections.

PMID- 19405881
TI  - Equine veterinarians affected yet resilient in sour economy.

PMID- 19405884
TI  - Effects of adjunct electroacupuncture on severity of postoperative pain in dogs
      undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk
      disease.
AB  - OBJECTIVE: To compare severity of postoperative pain in dogs undergoing
      hemilaminectomy because of acute thoracolumbar intervertebral disk disease
      treated with a combination of conventional analgesics and electroacupuncture
      (EAP) or with conventional analgesics alone. DESIGN: Controlled clinical trial.
      ANIMALS: 15 dogs undergoing surgery because of acute thoracolumbar disk disease.
      PROCEDURES: Dogs were alternately assigned to treatment (conventional analgesics
      and adjunct EAP) and control (conventional analgesics alone) groups. Analgesic
      treatment was adjusted as necessary by the attending clinician, who was not aware
      of group assignment. Pain scores were assigned 1, 3, and 12 hours after surgery
      and every 12 hours thereafter for 72 hours by the same individual who performed
      acupuncture treatments. RESULTS: Total dose of fentanyl administered during the
      first 12 hours after surgery was significantly lower in the treatment group than
      in the control group, but dosages of analgesics administered from 12 through 72
      hours after surgery did not differ between groups. Pain score was significantly
      lower in the treatment group than in the control group 36 hours after surgery,
      but did not differ significantly between groups at any other time. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results provided equivocal evidence that adjunct EAP
      might provide some mild benefit in regard to severity of postoperative pain in
      dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral
      disk disease.

PMID- 19405885
TI  - Gastric histopathologic abnormalities in dogs: 67 cases (2002-2007).
AB  - OBJECTIVE: To test the hypothesis that intestinal pathologic changes are often
      concurrent with gastric pathologic changes in dogs and to characterize the
      historical, physical, clinicopathologic, imaging, and endoscopic findings in dogs
      with gastric histopathologic abnormalities. DESIGN: Retrospective case series.
      ANIMALS: 67 dogs with gastric histopathologic abnormalities. PROCEDURES: Medical
      records from dogs that had undergone gastrotomy, gastroduodenoscopy, or
      gastroscopy between September 2002 and September 2007 were identified. Dogs were
      included in the study when histopathologic abnormalities were detected during
      evaluation of gastric tissue sections. History, clinical examination findings,
      results of diagnostic tests, diagnoses, treatments, and outcome were recorded for
      each dog. RESULTS: 67 dogs with gastric histopathologic abnormalities were
      included in the study. The most frequent clinical sign recorded was vomiting
      (36/67 [53.7%] dogs). The most common biochemical abnormality recorded was
      panhypoproteinemia (27/64 [42.2%] dogs). Lymphoplasmacytic gastritis was the most
      frequent histopathologic finding recorded (34/67 [50.7%] dogs). For dogs in which
      both intestinal biopsy specimens and gastric biopsy specimens were collected,
      concurrent pathologic changes were recorded in 43 of 60 (71.7%) dogs. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results of this study suggested that intestinal
      pathologic changes are commonly concurrent in dogs with gastric pathologic
      changes. This supports the practice of collecting both gastric and duodenal
      biopsy specimens every time gastroduodenoscopy is performed. Lymphoplasmacytic
      gastritis was the most commonly recorded gastric histopathologic finding and was
      often of minimal or mild severity.

PMID- 19405886
TI  - Effects of extracorporeal shock wave therapy on wounds of the distal portion of
      the limbs in horses.
AB  - OBJECTIVE: To evaluate the effects of focused, extracorporeal shock wave therapy
      (ESWT) on the healing of wounds of the distal portion of the limbs in horses.
      DESIGN: Randomized controlled trial. ANIMALS: 6 healthy adult horses. PROCEDURES:
      In each horse, a 4-cm-diameter full-thickness wound that included underlying
      periosteum was created on the dorsomedial aspect of each metacarpus and two 3-cm
      diameter full-thickness wounds that included underlying periosteum were created
      on the dorsomedial aspect of each metatarsus. One randomly selected metacarpal
      wound and a randomly selected pair of metatarsal wounds were treated once weekly
      with ESWT at an energy flux density of 0.11 mJ/mm(2). For metacarpal wounds, swab
      specimens were collected for bacterial culture on days 1, 2, and 3 and area of
      epithelialization and extent of wound contraction were measured at 3- to 4-day
      intervals. Metatarsal wounds were biopsied after 2 and 4 weeks, and
      immunohistochemical staining for vascular endothelial growth factor, transforming
      growth factor-beta1, and insulin-like growth factor-1 was performed. RESULTS:
      Results of bacterial culture, area of epithelialization, and percentage of wound
      contraction did not differ between treated and untreated wounds; however, healing
      time for treated wounds (mean, 76 days) was significantly shorter than healing
      time for untreated wounds (90 days). Staining intensity of growth factors did not
      differ significantly between treated and untreated wounds. CONCLUSIONS AND
      CLINICAL RELEVANCE: Findings suggested that ESWT may stimulate healing of wounds
      of the distal portion of the limbs in horses, although the mechanism by which
      healing was stimulated could not be identified.

PMID- 19405888
TI  - Comparison of three treatment regimens for sheep and goats with caseous
      lymphadenitis.
AB  - OBJECTIVE: To compare the effectiveness of 3 treatment regimens for small
      ruminants with caseous lymphadenitis. DESIGN: Randomized clinical trial. ANIMALS:
      44 client-owned sheep and goats. PROCEDURES: Aspirates were obtained from 48
      lesions of 44 enrolled animals and submitted for bacterial culture. Animals were
      randomly assigned to 1 of 3 treatment groups. Treatment for group A (n = 15
      lesions) consisted of opening, draining, and flushing the lesions and SC
      administration of procaine penicillin G. Treatment for group B (n = 15 lesions)
      consisted of closed-system lavage and intralesional administration of
      tulathromycin. Treatment for group C (n = 18 lesions) consisted of closed-system
      lavage and SC administration of tulathromycin. All animals were reexamined
      approximately 1 month after treatment, unless treatment failure was detected
      prior to that time. RESULTS: 43 animals with lesions had positive results
      (Corynebacterium pseudotuberculosis) for bacterial culture. Proportions of
      lesions that had resolution of infection by 1 month after treatment did not
      differ significantly among the treatment groups (group A, 13/14 [92.9%]; 95%
      confidence interval [CI], 69.5% to 99.6%; group B, 10/12 [83.3%]; 95% CI, 54.9%
      to 97.1%; and group C, 14/17 [82.4%]; 95% CI, 59.1% to 95.3%). CONCLUSIONS AND
      CLINICAL RELEVANCE: Acceptable alternatives to opening, draining, and flushing of
      lesions may exist for treatment of sheep and goats with caseous lymphadenitis.
      Use of tulathromycin and penicillin in this study constituted extralabel drug
      use, which would require extended withholding times before milk or meat of
      treated sheep and goats can be sold for human consumption.

PMID- 19405891
TI  - Prognostic indicators for nonambulatory cattle treated by use of a flotation tank
      system in a referral hospital: 51 cases (1997-2008).
AB  - OBJECTIVE: To evaluate clinical variables assessed during the first 24 hours of
      hospitalization as prognostic indicators for nonambulatory cattle treated by use
      of a flotation tank. DESIGN: Retrospective case series. ANIMALS: 51 nonambulatory
      cattle that underwent flotation treatment. PROCEDURES: Signalment, history, serum
      biochemical analyses, patient behavior during flotation, and outcome data were
      collected from medical records. Outcome was survival to discharge from the
      hospital or nonsurvival (death or euthanasia). Data were analyzed by use of
      Wilcoxon rank sum, Fisher exact, and chi(2) tests. RESULTS: 19 of 51 cattle
      survived. Survivors and nonsurvivors did not differ significantly with regard to
      median weight; age; stage of lactation; duration of recumbency prior to
      flotation; serum potassium, ionized calcium, or phosphate concentrations at
      admission to the hospital; or serum creatine kinase activity (value at admission
      to the hospital, highest value, and last recorded value). Cattle that were able
      to walk out of the tank after the first flotation treatment were 4.8 times as
      likely to survive as those that could not. Cattle that did not eat during
      flotation treatment were 1.9 times as likely to die as those that ate. Cattle
      that stood apparently normally on all limbs during the first flotation treatment
      were 2.9 times as likely to survive as those that had an asymmetric stance or
      were unable to stand. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that
      objective variables evaluated during the first 24 hours of hospitalization and
      flotation treatment are associated with outcome among nonambulatory cattle;
      findings might assist in logical decision making with respect to treatment
      options.

PMID- 19405894
TI  - Comparison of two fecal egg recovery techniques and larval culture for
      cyathostomins in horses.
AB  - OBJECTIVE: To compare the McMaster and centrifugal flotation techniques and
      larval culture for recovery of cyathostomin (small strongyle) eggs from the feces
      of horses. SAMPLE POPULATION: Fecal samples from 101 horses. PROCEDURES: In
      experiment I, homogenized fresh feces from a single horse were randomly
      subsampled by use of each technique for 10 replicates. In experiment II, samples
      from 43 horses that had no anthelmintic treatment were analyzed by use of
      McMaster, centrifugal flotation, and larval culture techniques. In experiment
      III, 57 horses were treated with an anthelmintic by owners, and fecal samples
      were analyzed as for experiment II. RESULTS: In experiment I, use of the McMaster
      technique recovered 72% of the eggs obtained by use of centrifugal flotation from
      paired subsamples. In experiment II, use of the McMaster technique recovered 81%
      of the eggs obtained by use of centrifugal flotation. Only cyathostomins resulted
      from individual larval cultures. In experiment III, 24 samples had negative
      results for all 3 tests, 18 samples had positive results only with larval
      cultures, and 15 samples had positive results of centrifugal flotation (only 5 of
      which had positive results via the McMaster technique). CONCLUSIONS AND CLINICAL
      RELEVANCE: Centrifugal flotation consistently was superior to the McMaster
      technique, especially at low fecal egg numbers. The combination of centrifugal
      flotation and larval culture may provide the best accuracy for evaluation of
      anthelmintic efficacy.

PMID- 19405893
TI  - Evaluation of changes in serum lipoprotein and apolipoprotein patterns in cows
      with ketosis.
AB  - OBJECTIVE: To detect changes in serum lipoprotein and apolipoprotein profiles via
      precipitation and electrophoresis in ketotic cows and in those cows treated with
      different methods. ANIMALS: 21 cows with clinical and subclinical ketosis, 7
      healthy cows in the early lactation period, and 7 healthy cows in the
      nonlactation period. PROCEDURES: Ketotic cows were allocated into 3 groups; the
      first group was treated with dextrose and dexamethasone, the second group with
      dextrose and prednisolone, and the third group with dextrose and insulin. The
      beta and alpha lipoproteins were precipitated with dextran sulfate-magnesium
      chloride in ketotic cows after treatment and healthy cows in the nonlactation and
      lactation periods. The serum samples, precipitates, and supernatants were
      examined via agarose gel electrophoresis for detection of alterations in serum
      lipoproteins. Subsequently, alterations in serum apolipoproteins were detected
      via SDS-PAGE of precipitates. RESULTS: Compared with serum beta and alpha
      lipoprotein concentrations in healthy cows during nonlactation, those in cows
      during lactation were higher; however, those in cows with ketosis were lower. The
      SDS-PAGE analysis of serum beta lipoproteins revealed that apolipoprotein E
      (approx 36 and 40 kDa) decreased in ketotic cows, in comparison with healthy cows
      in the nonlactation and lactation periods, but increased after treatment.
      Decreases in apolipo-protein B (approx 222 kDa), apolipoprotein A-I (19 and 24
      kDa), apolipoprotein A-IV (55 kDa), apolipoprotein C-III (8.8 and 10.2 kDa), and
      albumin (66 kDa) concentrations were detected in ketotic cows, in comparison with
      the healthy cows in the lactation period. CONCLUSIONS AND CLINICAL RELEVANCE:
      Serum lipoprotein and apolipoproteins may routinely be determined via
      precipitation and electrophoresis in the diagnosis and treatment of ketosis.

PMID- 19405889
TI  - Efficacy of feeding plasma-derived commercial colostrum replacer for the
      prevention of transmission of Mycobacterium avium subsp paratuberculosis in
      Holstein calves.
AB  - OBJECTIVE: To estimate the relative risk of paratuberculosis (Johne's disease
      [JD]) in calves fed a plasma-derived colostrum-replacement (CR) product versus
      raw bovine maternal colostrum (MC). STUDY DESIGN: Randomized controlled clinical
      trial. ANIMALS: 497 heifer calves born in 12 JD-endemic commercial Holstein dairy
      farms located in Minnesota and Wisconsin. PROCEDURES: Every calf was separated
      from its dam within 30 to 60 minutes after birth and systematically assigned to
      be fed raw bovine MC (control group, n = 261 calves) or CR (treatment group, 236
      calves). The calves were monitored to adulthood and tested for Mycobacterium
      avium subsp paratuberculosis (MAP) infection by use of an ELISA to detect serum
      antibodies against MAP and bacterial culture for MAP in feces at approximately
      30, 42, and 54 months of age. Weibull regression models were used to evaluate the
      effect of feeding CR (vs raw bovine MC) on the risk of developing JD infection.
      RESULTS: Calves fed CR at birth were less likely (hazard ratio = 0.559) to become
      infected with MAP (as determined by use of an ELISA, bacterial culture, or both
      diagnostic tests), compared with the likelihood for calves fed MC at birth.
      CONCLUSIONS AND CLINICAL RELEVANCE: This study revealed that feeding CR reduced
      the risk of developing MAP infection in Holstein calves born in JD-endemic herds,
      which implied that feeding raw bovine MC may be a source of MAP for calves.
      Plasma colostrum-replacement products may be an effective management tool for use
      in dairy herds attempting to reduce the prevalence of JD.

PMID- 19405895
TI  - Cardiopulmonary effects of diazepam-ketamine-isoflurane or xylazine-ketamine
      isoflurane during abdominal surgery in foals.
AB  - OBJECTIVE: To evaluate cardiopulmonary effects of anesthetic induction with
      diazepam and ketamine or xylazine and ketamine, with subsequent maintenance of
      anesthesia with isoflurane, in foals undergoing abdominal surgery. ANIMALS: 17
      pony foals. PROCEDURES: Foals underwent laparotomy at 7 to 15 days of age and
      laparoscopy 7 to 10 days later. Foals were randomly assigned to receive diazepam,
      ketamine, and isoflurane (D/K/Iso; n = 8) or xylazine, ketamine, and isoflurane
      (X/K/Iso; 9) for both procedures. RESULTS: During anesthesia for laparotomy,
      cardiac index, and mean arterial blood pressure ranged from 110 to 180 mL/kg/min
      and 57 to 81 mm Hg, respectively, in the D/K/Iso group and 98 to 171 mL/kg/min
      and 50 to 66 mm Hg, respectively, in the X/K/Iso group. Cardiac index, heart
      rate, and arterial blood pressures were significantly higher in the D/K/Iso
      group, compared with the X/K/Iso group. During anesthesia for laparoscopy,
      cardiac index and mean arterial blood pressure ranged from 85 to 165 mL/kg/min
      and 67 to 83 mm Hg, respectively, in the D/K/Iso group, and 98 to 171 mL/kg/min
      and 48 to 67 mm Hg, respectively, in the X/K/Iso group. Heart rates and arterial
      blood pressures were significantly higher in the D/K/Iso group, compared with the
      X/K/Iso group. There were no significant differences between groups during either
      experimental period for percentage end-tidal isoflurane, arterial blood gas
      partial pressures, or pH values. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthesia
      of foals for abdominal surgery with D/K/Iso was associated with less hemodynamic
      depression than with X/K/Iso.

PMID- 19405897
TI  - Influence of early conditioning exercise on the development of gross cartilage
      defects and swelling behavior of cartilage extracellular matrix in the equine
      midcarpal joint.
AB  - OBJECTIVE: To investigate the influence of early conditioning exercise on the
      development of gross cartilage defects and swelling behavior of cartilage
      extracellular matrix (ECM) in the midcarpal joint of horses. ANIMALS: 12
      Thoroughbreds. PROCEDURES: 6 horses underwent early conditioning exercise from
      birth to 18 months of age (CONDEX group), and 6 horses were used as control
      animals (PASTEX group). The horses were euthanized at 18 months of age, and the
      midcarpal joints were harvested. Gross defects of the cartilage surface were
      classified and mapped. Opposing surfaces of the third and radial carpal bones
      were used to quantify swelling behavior of the cartilage ECM. RESULTS: A wide
      range of gross defects was detected in the cartilage on the opposing surfaces of
      the bones of the midcarpal joint; however, there was no significant difference
      between the CONDEX and PASTEX groups. Similarly, no significant difference in
      swelling behavior of the cartilage ECM was evident between the CONDEX and PASTEX
      groups. CONCLUSIONS AND CLINICAL RELEVANCE: In the study reported here, we did
      not detect negative influences of early conditioning exercise on the prevalence
      of gross defects in cartilage of the midcarpal joint or the quality of the
      cartilage ECM as defined by swelling behavior. These results suggested that early
      conditioning exercise may be used without negative consequences for the midcarpal
      joint and the cartilage ECM of the third and radial carpal bones.

PMID- 19405896
TI  - Effect of remifentanil hydrochloride administered via constant rate infusion on
      the minimum alveolar concentration of isoflurane in cats.
AB  - OBJECTIVE: To evaluate the effects of increasing doses of remifentanil
      hydrochloride administered via constant rate infusion (CRI) on the minimum
      alveolar concentration (MAC) of isoflurane in cats. ANIMALS: 6 healthy adult
      cats. PROCEDURES: For each cat, 2 experiments were performed (2-week interval).
      On each study day, anesthesia was induced and maintained with isoflurane; a
      catheter was placed in a cephalic vein for the administration of lactated
      Ringer's solution or remifentanil CRIs, and a catheter was placed in the jugular
      vein for collection of blood samples for blood gas analyses. On the first study
      day, individual basal MAC (MAC(Basal)) was determined for each cat. On the second
      study day, 3 remifentanil CRIs (0.25, 0.5, and 1.0 microg/kg/min) were
      administered (in ascending order); for each infusion, at least 30 minutes elapsed
      before determination of MAC (designated as MAC(R0.25), MAC(R0.5), and MAC(R1.0),
      respectively). A 15-minute washout period was allowed between CRIs. A control MAC
      (MAC(Control)) was determined after the last remifentanil infusion. RESULTS: Mean
      +/- SD MAC(Basal) and MAC(Control) values at sea level did not differ
      significantly (1.66 +/- 0.08% and 1.52 +/- 0.21%, respectively). The MAC values
      determined for each remifentanil CRI did not differ significantly. However,
      MAC(R0.25), MAC(R0.5), and MAC(R1.0) were significantly decreased, compared with
      MAC(Basal), by 23.4 +/- 7.9%, 29.8 +/- 8.3%, and 26.0 +/- 9.4%, respectively.
      CONCLUSIONS AND CLINICAL RELEVANCE: The 3 doses of remifentanil administered via
      CRI resulted in a similar degree of isoflurane MAC reduction in adult cats,
      indicating that a ceiling effect was achieved following administration of the
      lowest dose.

PMID- 19405898
TI  - Evaluation of changes in cardiac biomarker concentrations and enzyme activities
      in serum after short- and long-duration transcutaneous cardiac pacing in dogs.
AB  - OBJECTIVE: To evaluate serum cardiac biomarker concentrations and selected enzyme
      activities in dogs with experimentally induced bradyarrhythmias after short- (1
      hour) and long- (3-hour) duration transcutaneous cardiac pacing (TCP). ANIMALS:
      10 healthy Beagles. PROCEDURES: In each dog, anesthesia was induced with propofol
      (5 mg/kg, IV) and maintained via inhalation of isoflurane in oxygen. To induce
      bradyarrhythmia, diltiazem was administered IV (20 to 50 mg/dog). Transcutaneous
      cardiac pacing was performed for 1 hour (5 dogs) or 3 hours (5 dogs) by use of an
      automated external cardiac pulse generator and a transdermal electrode. Serum
      concentrations of creatine kinase-MB fraction and cardiac troponin I and
      activities of aspartate transaminase, creatine kinase, and lactate dehydrogenase
      were evaluated the day before (baseline) and at intervals until 7 days after TCP.
      RESULTS: Increases (from baseline) in serum cardiac biomarker concentrations and
      enzyme activities were detected in the long-duration TCP group; changes in the
      short-duration TCP group were more minor and largely not significant. Although
      severity of myocardial and skeletal muscular injuries was apparently greater with
      greater duration of TCP, the injuries were not persistent; most variables were
      within reference range within 3 days after TCP. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that application of TCP for > 1 hour in dogs may
      cause myocardial and skeletal muscular injuries. Serum concentrations of creatine
      kinase-MB fraction and cardiac troponin I and activities of aspartate
      transaminase, creatine kinase, and lactate dehydrogenase should be more carefully
      monitored after TCP of > 1 hour's duration to evaluate potential myocardial
      damages.

PMID- 19405899
TI  - Use of signal analysis of heart sounds and murmurs to assess severity of mitral
      valve regurgitation attributable to myxomatous mitral valve disease in dogs.
AB  - OBJECTIVE: To investigate use of signal analysis of heart sounds and murmurs in
      assessing severity of mitral valve regurgitation (mitral regurgitation [MR]) in
      dogs with myxomatous mitral valve disease (MMVD). ANIMALS: 77 client-owned dogs.
      PROCEDURES: Cardiac sounds were recorded from dogs evaluated by use of
      auscultatory and echocardiographic classification systems. Signal analysis
      techniques were developed to extract 7 sound variables (first frequency peak,
      murmur energy ratio, murmur duration > 200 Hz, sample entropy and first minimum
      of the auto mutual information function of the murmurs, and energy ratios of the
      first heart sound [S1] and second heart sound [S2]). RESULTS: Significant
      associations were detected between severity of MR and all sound variables, except
      the energy ratio of S1. An increase in severity of MR resulted in greater
      contribution of higher frequencies, increased signal irregularity, and decreased
      energy ratio of S2. The optimal combination of variables for distinguishing dogs
      with high-intensity murmurs from other dogs was energy ratio of S2 and murmur
      duration > 200 Hz (sensitivity, 79%; specificity, 71%) by use of the auscultatory
      classification. By use of the echocardiographic classification, corresponding
      variables were auto mutual information, first frequency peak, and energy ratio of
      S2 (sensitivity, 88%; specificity, 82%). CONCLUSIONS AND CLINICAL RELEVANCE: Most
      of the investigated sound variables were significantly associated with severity
      of MR, which indicated a powerful diagnostic potential for monitoring MMVD.
      Signal analysis techniques could be valuable for clinicians when performing risk
      assessment or determining whether special care and more extensive examinations
      are required.

PMID- 19405900
TI  - Pancreatic response in healthy dogs fed diets of various fat compositions.
AB  - OBJECTIVE: To indirectly assess the pancreatic response in healthy dogs that were
      fed diets of different fat compositions with or without supplemental pancreatic
      enzymes and medium-chain triglycerides (MCTs). ANIMALS: 10 healthy adult dogs.
      PROCEDURES: Dogs were fed 4 diets once in random order at 1-week intervals; food
      was withheld from the dogs for > or = 12 hours prior to the feeding of each diet.
      Diets A and B contained 16% and 5% crude fat, respectively; diet C was composed
      of diet A with pancreatic enzymes; and diet D was composed of diet B with
      pancreatic enzymes and MCTs. Serum canine trypsin-like immunoreactivity (cTLI)
      and canine pancreatic lipase immunoreactivity (cPLI) concentrations were measured
      before (0 hours) and at 1 to 2 and 6 hours after feeding. Serum gastrin
      concentration was measured at 0 hours and at 5 to 10 minutes and 1 to 2 hours
      after feeding. A gastrin assay validation study was performed to confirm accuracy
      of test results in dogs. Data were analyzed by use of a repeated-measures general
      ANOVA. RESULTS: Serum cTLI, cPLI, or gastrin concentrations in the dogs did not
      differ among the different diets fed, among dogs, or over time. When multiple
      comparisons were analyzed, diet D caused the least amount of measurable
      pancreatic response, although this difference was not significant. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results did not indicate a significant effect of dietary
      fat content or addition of supplemental MCT oil or pancreatic enzymes in diets on
      serum cTLI, cPLI, or gastrin concentrations in healthy dogs.

PMID- 19405901
TI  - Assessment of cytologic evaluation of preputial epithelial cells as a diagnostic
      test for detection of adrenocortical disease in castrated ferrets.
AB  - OBJECTIVE: To determine whether results of cytologic evaluation of preputial
      epithelial cells correspond to results of a serum endocrine hormone assay and
      clinical signs associated with adrenocortical disease in castrated ferrets.
      ANIMALS: 13 clinically normal ferrets and 8 ferrets with signs of adrenocortical
      disease. PROCEDURES: Blood and preputial lavage samples were collected from each
      ferret. Serum samples were submitted to the University of Tennessee Veterinary
      Diagnostic Laboratory for performance of an endocrine hormone assay. Differential
      epithelial cell counts were performed on preputial lavage samples to determine
      the percentage of cornified cells. Results of cytologic evaluation were compared
      with results of the endocrine hormone assay and clinical status of ferrets.
      RESULTS: The percentage of cornified preputial epithelial cells was not
      significantly correlated with serum 17B-estradiol or androstenedione
      concentration but was significantly correlated with serum 17-hydroxyprogesterone
      concentration (r = 0.60). The percentage of cornified preputial epithelial cells
      was higher in ferrets with clinical signs of adrenocortical disease (mean +/- SD,
      71.3 +/- 16.9%) than in clinically normal ferrets (55.5 +/- 19.0%). CONCLUSIONS
      AND CLINICAL RELEVANCE: Cornification of preputial epithelial cells was
      correlated with an increase in serum 17-hydroxyprogesterone concentration as well
      as clinical signs of adrenocortical disease in castrated ferrets. Additional
      investigation is needed to elucidate the mechanism of preputial epithelial cell
      cornification in castrated ferrets.

PMID- 19405902
TI  - Effects of low-dose oligofructose treatment administered via nasogastric
      intubation on induction of laminitis and associated alterations in glucose and
      insulin dynamics in horses.
AB  - OBJECTIVE: To ascertain whether laminitis can be induced via administration of
      oligofructose (OF) at doses of 5.0 and 7.5 g/kg in horses and to assess glucose
      and insulin dynamics before and after treatment. ANIMALS: 19 adult horses.
      PROCEDURES: Horses were fed OF (1.0 g/kg) mixed with oats for 6 days.
      Oligofructose at doses of 5.0 and 7.5 g/kg was then mixed with 4 L of water and
      administered (0 hours) to 8 (group A) and 4 (group B) horses, respectively, via
      nasogastric intubation; 8 horses received water alone. One horse in group A that
      did not develop laminitis was subsequently treated again and included in group B.
      Before and at intervals after treatment, resting plasma glucose and serum insulin
      concentrations were measured and frequently sampled IV glucose tolerance tests
      were performed. Area under the glucose curve (AUCg) and area under the insulin
      curve (AUCi) were calculated, and minimal model analyses were performed. RESULTS:
      3 of 8 horses in group A and all 4 horses in group B developed laminitis.
      Significant treatment-time effects were detected for resting plasma glucose
      concentrations and AUCg. Among horses in group A, mean AUCg values at 24 and 48
      hours were 34% and 32% higher, respectively, than the mean value at 24 hours.
      Treatment groups did not differ significantly with respect to resting serum
      insulin concentration, AUCi, or minimal model analysis results. CONCLUSIONS AND
      CLINICAL RELEVANCE: In horses, laminitis can be induced and glucose dynamics
      altered via nasogastric administration of 5.0 g of OF/kg. An alteration in
      insulin dynamics was not detected following treatment with OF.

PMID- 19405903
TI  - Kinetics of inhibition of purified bovine neutrophil matrix metalloproteinase 9
      by low-molecular-weight inhibitors.
AB  - OBJECTIVE: To measure the effects of lowmolecular-weight inhibitors on the
      activity of bovine neutrophil matrix metalloproteinase 9 (MMP-9). SAMPLE
      POPULATION: Bovine MMP-9 purified from bovine neutrophilconditioned medium.
      PROCEDURES: Neutrophils were degranulated by stimulation with phorbol ester.
      Enzyme purification was performed by use of gelatin affinity and gel-filtration
      chromatography. Activated enzyme was incubated with inhibitors prior to addition
      of substrate (gelatin fluorescein conjugate or fluorogenic peptide). Rates of
      enzymatic cleavage were determined by monitoring fluorescence as the reactions
      progressed. Values of IC(50) (molar concentration of compound that inhibits
      specific activity by 50%) and K(I) (in vitro inhibition constant) were
      determined. RESULTS: Rates of enzymatic activity of monomeric and dimeric bovine
      MMP-9 measured by use of gelatin and peptide substrates were linear with respect
      to time and concentrations of enzyme and substrate. The MMP-9 was potently
      inhibited by hydroxamic acids (IC(50) for gelatin, 29.2 to 55.7 nM; IC(50) for
      peptide, 4.8 to 24.6 nM; K(I), 0.2 to 0.5 nM), whereas tetracyclines (IC(50) for
      gelatin, 30.1 to 112.7 MM; IC(50) for peptide, 48.0 to 123.8 MM; K(I), 25.2 to
      61.4 microM) and chlorhexidine (IC(50) for gelatin, 139.1MM; IC(50) for peptide,
      672.5MM to 1.7 mM; K(I), 495.0 to 663.0 MM) had limited inhibition. Gelatinase
      specific inhibitor SB-3CT had intermediate potency (IC(50) for peptide, 185.0 to
      290.0 nM; K(I), 66.5 to 86.0 nM). CONCLUSIONS AND CLINICAL RELEVANCE: Bovine MMP
      9 was potently inhibited by hydroxamic acids and gelatinase inhibitor. These
      compounds may be useful as modulators of neutrophil-mediated protease activity in
      cattle.

PMID- 19405904
TI  - Assessment of clotrimazole gels for in vitro stability and in vivo retention in
      the frontal sinus of dogs.
AB  - OBJECTIVE: To evaluate the stability and retention of viscous formulations of the
      antifungal drug clotrimazole in vitro and to evaluate retention times,
      absorption, and histologic response to these compounds when placed in the frontal
      sinus of dogs. ANIMALS: 6 male Beagles. PROCEDURES: 1% clotrimazole gels were
      formulated with hydroxypropyl cellulose, poloxamer, and carboxymethylcellulose
      sodium bases. Commercially available 1% clotrimazole creams were also evaluated.
      Each compound was incubated at 37 degrees C in a funnel. Volume retained and
      clotrimazole stability were evaluated for 4 weeks. Six compounds were then chosen
      for in vivo evaluation. The frontal sinuses of 6 dogs were filled with 1 of the 6
      compounds. Computed tomographic evaluation was performed weekly for up to 4 weeks
      to evaluate gel retention. Blood samples were collected to evaluate clotrimazole
      absorption. Following euthanasia, sinuses were examined histologically. RESULTS:
      Commercially available clotrimazole creams were not retained in funnels in vitro.
      In vivo, hydroxypropyl cellulose- and carboxymethylcellulose-based gels resulted
      in the most severe inflammatory response and were retained the longest. Poloxamer
      based gels had a shorter retention time and were associated with less
      inflammation. Clotrimazole was minimally absorbed. Despite a marked inflammatory
      response to several of the clotrimazole-containing gels, no notable adverse
      clinical responses were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Poloxamer
      gels had the most promise for improving drug contact within the frontal sinus of
      dogs, while limiting the inflammatory response. Poloxamer gels have the
      additional benefit of improved handling as a result of reverse gelation (ie, they
      gel when warmed to 37 degrees C).

PMID- 19405905
TI  - Microsatellite loci in urine supernatant and stored samples from racehorses.
AB  - OBJECTIVE: To evaluate whether urine supernatant contains amplifiable DNA and to
      determine factors that influence genotyping of samples from racehorses after
      storage and transportation. SAMPLE POPULATION: 580 urine, 279 whole blood, and 40
      plasma samples obtained from 261 Thoroughbreds and Standardbreds. PROCEDURES:
      Genomic DNA was isolated from stored blood and urine samples collected from
      racehorses after competition. Quantified DNA was evaluated to determine whether 5
      equine microsatellite loci (VHL20, HTG4, AHT4, HMS6, and HMS7) could be amplified
      by use of PCR techniques. Fragment size of each amplified locus was determined by
      use of capillary electrophoresis. RESULTS: High-molecular-weight and amplifiable
      DNA were recovered from refrigerated blood samples, but recovery from urine
      varied. Deoxyribonucleic acid was recovered from both urine supernatant and
      sediment. Freeze-thaw cycles of urine caused accumulation of amplifiable DNA in
      the supernatant and clearance of naked DNA. Repeated freeze-thaw cycles
      significantly decreased DNA yield and induced DNA degradation, which resulted in
      failure to detect microsatellite loci. Select drugs detected in test samples did
      not affect PCR amplification. Contaminants in DNA isolates inhibited PCR
      amplification and resulted in partial microsatellite profiles. CONCLUSIONS AND
      CLINICAL RELEVANCE: Properly stored urine and blood samples were successfully
      genotyped, but subjecting urine to freeze-thaw cycles was most detrimental to the
      integrity of DNA. Increasing the volume of urine used improved recovery of DNA.

PMID- 19405906
TI  - Effects of treadmill inclination on electromyographic activity and hind limb
      kinematics in healthy hounds at a walk.
AB  - OBJECTIVE: To evaluate the effect of treadmill incline on muscle activity and
      joint range of motion (ROM) in hind limbs of dogs. ANIMALS: 8 purpose-bred
      healthy adult hounds. PROCEDURES: Activities of the hamstring (semimembranosus,
      semitendinosus, and biceps femoris muscles), gluteal (superficial, middle, and
      deep gluteal muscles), and quadriceps (femoris, vastus lateralis, vastus
      intermedius, and vastus medialis muscles) muscle groups and hip and stifle joint
      ROM were measured with surface electrogoniometric and myographic sensors in
      hounds walking on a treadmill at 0.54 m/s at inclines of 5%, 0%, and -5% in
      random order. Mean electromyographic activities and mean ROMs at each inclination
      were compared for swing and stance phases. RESULTS: Treadmill inclination did not
      affect duration of the stance and swing phases or the whole stride. When
      treadmill inclination was increased from -5% to 5%, hip joint ROM increased and
      the degree of stifle joint extension decreased significantly. In the beginning of
      the stance phase, activity of the hamstring muscle group was significantly
      increased when walking at a 5% incline versus a 5% decline. In the end of the
      stance phase, that activity was significantly increased when walking at a 5%
      incline versus at a 5% decline or on a flat surface. Activity of the gluteal and
      quadriceps muscle groups was not affected when treadmill inclination changed.
      CONCLUSIONS AND CLINICAL RELEVANCE: Treadmill inclination affected joint
      kinematics only slightly. Walking on a treadmill at a 5% incline had more
      potential to strengthen the hamstring muscle group than walking on a treadmill
      with a flat or declined surface.

PMID- 19405907
TI  - Pharmacokinetics and bioavailability of metformin in horses.
AB  - OBJECTIVE: To determine pharmacokinetics and oral bioavailability of metformin in
      healthy horses. ANIMALS: 4 adult horses. PROCEDURES: 6 g of metformin was
      administered 3 times IV and PO (fed and unfed) to each horse, by use of a
      crossover design, with a 1-week washout period between treatments. Plasma
      metformin concentration was determined via high-pressure liquid chromatography.
      RESULTS: Mean +/- SD distribution half-life of metformin following IV
      administration was 24.9 +/- 0.4 minutes with a volume of distribution of 0.3 +/-
      0.1 L/kg. Mean area under the curve was 20.9 +/- 2.0 h.microg/mL for IV
      administration; PO administration resulted in area under the curves of 1.6 +/-
      0.4 h.microg/mL in unfed horses and 0.8 +/- 0.2 h.microg/mL in fed horses.
      Bioavailability was determined to be approximately 7.1 +/- 1.5% in unfed horses
      and 3.9 +/- 1.0% in fed horses. The maximal concentration following PO
      administration in unfed horses was 0.4 +/- 0.1 microg/mL with a time at maximal
      concentration of 0.9 +/- 0.1 hours. In fed horses, maximal concentration was
      reduced to 0.3 +/- 0.04 microg/mL with a time at maximal concentration at 1.3 +/-
      0.3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: The low bioavailability of
      metformin may explain the reported lack of clinical success in improving insulin
      sensitivity with metformin treatment in horses. Dosages and dose intervals
      previously used may have been insufficient to achieve plasma concentrations of
      drug comparable to the therapeutic range achieved in humans. Therefore, a larger
      and more frequently administered dose may be required to fully evaluate efficacy
      of metformin in horses.

PMID- 19405908
TI  - Effects of long-term extracorporeal blood perfusion of the distal portion of
      isolated equine forelimbs on metabolic variables and morphology of laminar
      tissue.
AB  - OBJECTIVE: To establish an ex vivo model of blood perfusion in the distal portion
      of isolated equine forelimbs that closely represents the in vivo situation in the
      laminar tissue of the hoof. SAMPLE POPULATION: 18 forelimbs collected from 9
      healthy adult horses following slaughter at a licensed abattoir. PROCEDURES: The
      distal portion of isolated equine forelimbs from 9 horses were perfused under
      physiologic conditions over a period of 6, 8, and 10 hours with autologous blood.
      To determine cell viability in perfused tissues, indicators for metabolism
      (lactate generation and glucose and oxygen consumption) as well as indicators for
      cell damage (potassium concentration and lactate dehydrogenase activity) were
      examined at 1-hour intervals from samples of the perfusate. Weight gain in the
      forelimb was used to determine the edema index. After perfusion, light and
      electron microscopic examinations of laminar tissue specimens were performed.
      RESULTS: During hemoperfusion of the isolated forelimbs, mean +/- SD glucose
      consumption was 197.4 +/- 65.1 mg/h, lactate generation was 1.84 +/- 0.79 mmol/h,
      and oxygen consumption was 6.4 x 10(-6) +/- 8.9 x 10(-5) mL.g(-1).min(-1).
      Neither an efflux of potassium into the perfusate nor a relevant increase of the
      lactate dehydrogenase activity was detected, indicating low amounts of cellular
      damage in the perfused tissues. Weight gain of forelimbs was 1.02 +/- 0.95%.
      Histologic and ultrastructural appearance of the laminar tissue revealed no signs
      of tissue damage. CONCLUSIONS AND CLINICAL RELEVANCE: Isolated equine limbs were
      perfused under physiologic conditions over a period of < or = 10 hours without
      structural damage to the laminar tissue.

PMID- 19405910
TI  - Kinetic analysis of human protein arginine N-methyltransferase 2: formation of
      monomethyl- and asymmetric dimethyl-arginine residues on histone H4.
AB  - Protein arginine N-methyltransferases (PRMTs) methylate arginine residues within
      proteins using S-adenosyl-L-methionine (AdoMet) to form S-adenosyl-L-homocysteine
      and methylarginine residues. All PRMTs produce omega-NG-monomethylarginine (MMA)
      residues and either asymmetric omega-N(G),N(G)-dimethylarginine (aDMA) or
      symmetric omega-N(G),N'(G)-dimethylarginine (sDMA) residues, referred to as Type
      I or Type II activity respectively. Here we report methylation activity from
      PRMT2 and compare it with PRMT1 activity using UPLC-MS/MS (ultra-performance
      liquid chromatography-tandem MS), gel electrophoresis, and thin-layer
      chromatography. We show that PRMT2 is a Type I enzyme and that the ratio of aDMA
      to MMA produced by PRMTs 1 and 2 is dependent on the substrate, regardless of
      rate or K(m), suggesting that the reactions for both enzymes are distributive
      rather than processive. Using UPLC-MS/MS we find that, for PRMT2, the
      dissociation constant (KAs) and K(m) of AdoMet and the Km of histone H4 are
      similar to values for PRMT1, whereas the PRMT2 k(cat) is 800-fold less than the
      PRMT1 k(cat). Although PRMT2 activity is substantially lower than PRMT1 in vitro,
      the fact that both enzymes selectively methylate histone H4 suggest that PRMT2,
      like PRMT1, may act as a transcription co-activator through this modification.

PMID- 19405909
TI  - Thioesterase superfamily member 2 (Them2)/acyl-CoA thioesterase 13 (Acot13): a
      homotetrameric hotdog fold thioesterase with selectivity for long-chain fatty
      acyl-CoAs.
AB  - Them2 (thioesterase superfamily member 2) is a 140-amino-acid protein of unknown
      biological function that comprises a single hotdog fold thioesterase domain. On
      the basis of its putative association with mitochondria, accentuated expression
      in oxidative tissues and interaction with StarD2 (also known as
      phosphatidylcholine-transfer protein, PC-TP), a regulator of fatty acid
      metabolism, we explored whether Them2 functions as a physiologically relevant
      fatty acyl-CoA thioesterase. In solution, Them2 formed a stable homotetramer,
      which denatured in a single transition at 59.3 degrees C. Them2 exhibited
      thioesterase activity for medium- and long-chain acyl-CoAs, with Km values that
      decreased exponentially as a function of increasing acyl chain length. Steady
      state kinetic parameters for Them2 were characteristic of long-chain mammalian
      acyl-CoA thioesterases, with minimal values of Km and maximal values of kcat/Km
      observed for myristoyl-CoA and palmitoyl-CoA. For these acyl-CoAs, substrate
      inhibition was observed when concentrations approached their critical micellar
      concentrations. The acyl-CoA thioesterase activity of Them2 was optimized at
      physiological temperature, ionic strength and pH. For both myristoyl-CoA and
      palmitoyl-CoA, the addition of StarD2 increased the kcat of Them2. Enzymatic
      activity was decreased by the addition of phosphatidic acid/phosphatidylcholine
      small unilamellar vesicles. Them2 expression, which was most pronounced in mouse
      heart, was associated with mitochondria and was induced by activation of
      PPARalpha (peroxisome-proliferator-activated receptor alpha). We conclude that,
      under biological conditions, Them2 probably functions as a homotetrameric long
      chain acyl-CoA thioesterase. Accordingly, Them2 has been designated as the 13th
      member of the mammalian acyl-CoA thioesterase family, Acot13.

PMID- 19405912
TI  - Anti-oxidant enzymes and related elements in term and preterm newborns.
AB  - BACKGROUND: Although oxidative stress-related diseases mostly affect neonates
      with extremely low birthweight, healthy preterm newborns might also be at risk of
      oxidative damages. The aim of the present study was to verify this possibility.
      METHODS: Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), erythrocyte glutathione
      peroxidase (GSHPx) and superoxide dismutase (SOD), plasma and erythrocyte
      concentrations of selenium, zinc and copper were measured until 100 days of life
      in 30 preterm infants with mean +/- SD birthweight and gestational age of 1605 +/
      122 g and 34.5 +/- 0.5 weeks. The control group included 30 term infants with
      birthweight 3123 158 g and gestational age 39.6 0.7 weeks. RESULTS: Throughout
      the study period urinary 8-OHdG, taken as a marker of oxidative stress, was
      significantly higher in the preterm than in the term group. Up until 20 days of
      life, GSHPx activity was significantly lower in the preterm than in the term
      infants but this was not associated with any apparent selenium deficiency.
      Conversely, up until 100 days, preterm infants had significantly reduced SOD
      levels that appeared to reflect a shortage of the elements needed for this
      enzyme's activity, notably copper, the plasma concentrations of which were
      constantly and significantly below the control values. CONCLUSION: The
      nutritional status of the elements related to the anti-oxidant enzymes,
      especially zinc and copper, should be carefully assessed in preterm infants, even
      if their birthweight is not extremely low.

PMID- 19405913
TI  - Autoantibody to heterogeneous nuclear ribonucleoprotein-A2 (RA33) in juvenile
      idiopathic arthritis: clinical significance.
AB  - BACKGROUND: Objective biomarkers are needed for early diagnosis of juvenile
      idiopathic arthritis (JIA). Anti-A33 antibodies are considered good markers for
      adult rheumatoid arthritis (RA), but little information is available on their
      occurrence in JIA. The aim of the present study was therefore to investigate the
      value of anti-RA33 for diagnosis of JIA (both early and established disease), and
      its relation to markers of disease activity, and bone resorption. SUBJECTS: This
      case-control study was conducted on 34 children with JIA. Ten patients with
      arthritis of short duration (<6 weeks) were included, as undifferentiated
      arthritis. Forty-four age- and sex- matched healthy children served as controls.
      Beside evaluation and assessment of disease activity, urinary calcium, serum
      parathyroid hormone and serum anti-RA33 were measured in included subjects.
      Joints were examined radiologically and modified Larsen index (LI) was estimated.
      RESULTS: During follow up, eight of the patients with undifferentiated arthritis
      were diagnosed as having early JIA. Patients with JIA (early and established
      cases) had higher anti-RA33 levels than the control group (z = 6.04, 3.95,
      respectively). A total of 66.7% of the patients were positive for anti-RA33,
      results were comparable in early and established cases. Anti-RA33 values were
      correlated to disease activity (clinical and laboratory), to laboratory markers
      (urinary calcium, parathyroid hormone levels) and radiological evidence (LI) of
      bone resorption (r = 0.95, 0.63, 0.94, respectively). CONCLUSION: Anti-RA33 is
      detected in two-thirds of JIA patients and occurs with comparable frequency early
      in the disease. Its levels are correlated to disease activity and markers of bone
      resorption and it seems to convey diagnostic and prognostic insights for
      appropriate management.

PMID- 19405914
TI  - Molecular analysis of the SMN and NAIP genes in Iranian spinal muscular atrophy
      patients.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular
      disorder characterized by degeneration of spinal cord anterior horn cells,
      leading to muscular atrophy. SMA is clinically classified into three subgroups
      based on the age of onset and severity. The majority of patients with SMA have
      homozygous deletions of exons 7 and 8 of the survival motor neuron (SMN) gene.
      The purpose of the present study was to determine the frequency of SMN and
      neuronal apoptosis inhibitory protein (NAIP) gene deletions in Iranian SMA
      patients. Experience in prenatal diagnosis of SMA in this population is also
      reported. METHODS: To study the frequency of deletions of SMN and NAIP genes in
      an Iranian sample group, 75 unrelated SMA patients (54 type I, eight type II and
      13 type III) were analyzed according to the methods described by van der Steege
      et al and Roy et al. RESULTS: Homozygous deletion of SMN1 exons 7 and/or 8 were
      identified in 68 out of 75 patients (90%). Deletion of exon 5 of the NAIP gene
      was found in 40/54 of type I, 2/8 of type II and 1/13 of type III patients.
      CONCLUSIONS: Deletion of the SMN1 gene is a major cause of SMA in Iran, and NAIP
      gene deletions were common in the present patients with type I SMA. Also, the
      incidence of NAIP deletion is higher in more severe SMA.

PMID- 19405915
TI  - Dietary chloride deficiency due to new liquid nutritional products.
AB  - BACKGROUND: In infants the ingestion of chloride-deficient formulas was
      previously reported to cause hypochloremic metabolic alkalosis and hypokalemia,
      which is referred to as dietary chloride deficiency syndrome. Since that time,
      however, dietary chloride deficiency has not been commonly recognized. The aim of
      the present study was to evaluate the clinical features of dietary chloride
      deficiency syndrome caused by the ingestion of newly marketed liquid nutritional
      products. METHODS: This was a retrospective chart review of 59 patients with
      severe motor and intellectual disability (SMID); they had been given newly
      marketed liquid nutritional products that were later found to be chloride
      deficient. RESULTS: Eight-nine weeks after changing to the new liquid nutritional
      products, clinical symptoms and laboratory abnormalities were noted. The main
      clinical finding was weight loss; 22% of subjects lost >5% of their bodyweight. A
      small number of the subjects had a mild bowel movement disorder; diarrhea and
      constipation were found in six and three patients, respectively. Hyponatremia,
      hypokalemia, and hypochloremia occurred in 33.9%, 44.5%, and 50.8%, respectively.
      CONCLUSIONS: Chloride-deficient liquid nutritional products can cause weight
      loss, hypochloremic metabolic alkalosis, and hypokalemia in persons with severe
      motor and intellectual disability.

PMID- 19405916
TI  - Clinical or radiologic measurements and 3-D gait analysis in children with pes
      planus.
AB  - BACKGROUND: Static measurement in clinical and radiologic evaluation is often
      used in assessment of pes planus, but it is important to know whether pes planus
      leads to abnormal gait pattern. The purpose of the present study was to assess
      the clinical and radiologic findings of children with pes planus and the
      relationship between clinical, radiologic findings and parameters obtained in 3-D
      gait analysis. METHODS: Thirteen children with pes planus were selected. Physical
      measurements included femoral anteversion, internal and external rotation, thigh
      foot angle (TFA), and resting calcaneal stance position (RCSP). Radiologic
      measurements included talo-calcaneal angle (TCA), talometatarsal angle (TMA),
      calcaneal pitch, and forefoot adduction on simple X-ray, and femoral anteversion,
      tibial torsion and rotation on computed tomography (CT). 3-D gait analysis was
      also performed and kinetic and kinematic data were obtained in sagittal, frontal,
      and transverse plane. The correlation between clinical, radiologic, and gait
      analysis data was investigated. RESULTS: RCSP was found to be significantly
      correlated with TMA. TMA was also correlated with TCA. TCA on simple X-ray was
      correlated with maximal internal and external rotation angle of the knee joint on
      gait analysis. CONCLUSION: TMA was the factor most related to degree of calcaneal
      valgus measured on physical exam. Larger TCA contributed to decreased maximal
      external rotation and increased maximal internal rotation in gait cycle. Clinical
      or radiological methods, however, had very limited ability to predict gait
      deviance of pes planus.

PMID- 19405917
TI  - Is thrombocytopenia suggestive of organism-specific response in neonatal sepsis?
AB  - BACKGROUND: It is controversial whether thrombocytopenia is suggestive of one (or
      more) causative agents of neonatal sepsis: a low platelet count has been related
      in turn to Gram-positive, Gram-negative or fungal sepsis. METHODS: A
      retrospective, cohort study on 514 very low-birthweight (VLBW) neonates admitted
      over a 9 year period to a large tertiary neonatal intensive care unit (NICU) in
      Italy was carried out. Through database search, data on platelet counts, sepsis,
      clinical course, and microbiological culture were collected and analyzed.
      Statistical analysis was performed to look for significant association between
      thrombocytopenia and sepsis caused by different (Gram-positive, Gram-negative or
      fungal) organisms. RESULTS: Sepsis diagnosed on microbiological criteria occurred
      in 197 of 514 VLBW neonates (38.3%), and thrombocytopenia (at least one finding
      of platelet count <80,000/mm(3)) was detected in 34 (17.2%) of the 197 septic
      infants. Thrombocytopenia occurred in 10 of 51 neonates with fungal sepsis
      (19.6%), and in 24 of 146 with bacterial sepsis (16.4%; P = 0.37). The difference
      was not significant when clustering for sepsis caused by Gram-positive (nine
      thrombocytopenic of 51 with Gram-positive sepsis, 17.6%; P = 0.40) and Gram
      negative organisms (15/95, 15.7%; P = 0.22), or when considering only coagulase
      negative Staphylococcus sepsis (6/37, 16.2%; P = 0.25). CONCLUSIONS: In contrast
      with previous reports, thrombocytopenia might not be an organism-specific marker
      of sepsis. Caution should be maintained in relating a low platelet count to any
      infectious agent (or group of agents) in preterm VLBW neonates.

PMID- 19405918
TI  - Sensitivity of rapid immunoassay for influenza A and B in the early phase of the
      disease.
AB  - BACKGROUND: Immunochromatography (IC) tests are often used for the rapid
      diagnosis of influenza. Once influenza is diagnosed, an anti-influenza drug can
      be administered. Physicians claim, however, that they are not sufficiently
      sensitive, especially in the early phase of the disease. The aim of the present
      study was therefore to analyze the sensitivity of the IC test from the standpoint
      of virology. METHODS: To evaluate the sensitivity of the IC test statistically,
      736 nasopharyngeal specimens were subjected to the IC test and virus isolation
      (VI). The IC test (+) specimens were compared with VI (+) specimens in the early
      phase after fever onset. Amounts of the virus in IC(-)VI(+) specimens were
      compared with those in IC(+)VI(+) specimens on real-time reverse transcriptase
      polymerase chain reaction. The isolated viruses from these specimens were
      subjected to the IC test at the same dose. The nucleotide sequences of NP genes
      were compared. RESULTS: The IC test was less sensitive for diagnosis in the early
      phase of the disease. Amounts of virus were significantly lower in IC(-)VI(+)
      specimens than in IC(+)VI(+) specimens. No variations were observed in the
      isolated viruses. CONCLUSIONS: The IC test is not sufficiently sensitive owing to
      the low amount of virus in the nasopharyngeal tract in the early phase of the
      disease. Influenza should be diagnosed on the basis of clinical symptoms within 1
      day after the fever onset.

PMID- 19405919
TI  - Risk factors for neurological complications in complete hemolytic uremic syndrome
      caused by Escherichia coli O157.
AB  - BACKGROUND: The aim of the present study was to investigate the predictive
      parameters for encephalopathy in complete hemolytic uremic syndrome (HUS) in a
      large outbreak of O157: H7 infection in 1996. METHODS: A total of 182 inpatients,
      71 of whom had complete HUS, including 12 patients with neurological
      complications, and 46 colitis patients were studied. Presenting signs and
      symptoms (n = 115) and laboratory data (n = 69) were analyzed using monovariate
      and multivariate analysis. RESULTS: After adjusting for age and gender, logistic
      regression showed that presenting symptoms such as bloody diarrhea (odds ratio
      [OR] = 7.39), proteinuria (OR = 6.16), hematuria (OR = 8.31), oliguria (OR =
      17.4) and a pale face (OR = 10.7) were useful for predicting complete HUS. Also,
      increased white blood cell counts >12,000 microL/mL (OR = 10.0) and C-reactive
      protein >1.5 mg/dL (OR = 7.39) at the onset of infection, were useful as
      predictive laboratory parameters. To predict neurological complications in
      complete HUS patients, the average daily increase of lactate dehydrase >1200 IU/L
      per day (OR = 26.3) and creatinine >0.5 mg/dL per day (OR = 12) were found to be
      useful on multivariate logistic regression. CONCLUSION: There are useful
      predictive clinical factors for neurological complications in complete HUS.

PMID- 19405920
TI  - Efficacy of micafungin in treating four premature infants with candidiasis.
AB  - BACKGROUND: Although clinical experience in neonates with candidiasis exists for
      amphotericin B and fluconazole, these standard treatments are often hindered by
      drug-associated toxicity or development of resistant strains. The aim of the
      present study was therefore to investigate the efficacy and tolerability of a new
      antifungal agent, micafungin (MCFG), for treating Candida infections in premature
      infants. METHODS: This was a retrospective cohort study. Premature infants
      diagnosed with Candida infections from October 2003 to July 2004 were brought to
      the neonatal intensive care unit at the Center of Perinatal Medicine, Nara
      Medical University Hospital. Four newborns were given 0.5-1.0 mg/kg per day
      micafungin. RESULTS: Four premature infants (mean +/- SD gestational age, 24.1 +/
      0.9 weeks; mean +/- SD birthweight, 579.3 +/- 80.5 g) experienced complications
      from Candida infection; two cases of the fungal infection were caused by Candida
      glabrata and two cases were caused by Candida albicans. MCFG was administered at
      0.5 or 1.0 mg/kg per day (mean dosage days, 9.8 +/- 3.1 days) and it decreased
      beta-D-glucan levels while improving clinical symptoms in all cases.
      Additionally, there were no apparent side-effects. CONCLUSION: MCFG is both
      effective and tolerable for use in premature infants suffering from Candida
      infections.

PMID- 19405921
TI  - Epidemiology of neonatal sepsis in South Korea.
AB  - BACKGROUND: Neonatal sepsis is a severe clinical syndrome characterized by
      systemic signs of infection, shock and system organ failure; diagnosis is
      confirmed on positive culture from a normally sterile site(s). There are few
      reports comparing incidence, mortality, and risk factors between clinically
      diagnosed sepsis and that confirmed by culture. METHODS: All infants diagnosed
      with early- (within first 72 h after birth) or late-onset (72 h-4 weeks after
      birth) neonatal sepsis between 1997 and 1999 from four neonatal centers in South
      Korea, were investigated. RESULTS: The estimated incidence rate of neonatal
      sepsis during the 3 years was 30.5 per 1000 live births for clinical sepsis and
      6.1 per 1000 live births for sepsis with positive culture, with case-fatality
      rates of 4.7% and 2.2%, respectively. When only early-onset sepsis was
      considered, the incidence and fatality rates were 25.1 per 1000 live births and
      6.1% for clinical sepsis, and 4.3 per 1000 live births and 2.5% for culture
      confirmed sepsis, respectively. For the 179 patients (185 causative organisms) of
      proven sepsis, Staphylococcus spp. including S. aureus were the most frequent
      isolates. In early-onset clinical sepsis, having very low birthweight (<or=1500
      g), a low Apgar score at 5 min (<or=7), and being male were related to higher
      rates of case-fatality (relative risk: 11.3, 6.8 and 2.5, respectively).
      CONCLUSIONS: Clinical sepsis was more common than culture-confirmed sepsis and
      had a higher case-fatality rate. It seems prudent to take rapid and decisive
      steps toward better management of the high-risk group whether the sepsis is
      clinically diagnosed or culture confirmed.

PMID- 19405922
TI  - Comparison of neonatal outcome for inborn and outborn very low-birthweight
      preterm infants.
AB  - BACKGROUND: The aim of the present study was to compare the neonatal outcome of
      very low-birthweight (VLBW) preterm infants with regard to inborn and outborn
      status in a medical center of Southern Taiwan, where short-distance neonatal
      transport is the rule and maternal transport was not well established. METHODS:
      This retrospective study included outborn VLBW preterm infants admitted to the
      neonatal intensive care unit of Chang Gung Memorial Hospital at Kaohsiung after
      neonatal transport during the period from 1999 through 2003. An equal number of
      inborn preterm infants matched for gender and birthweight were included as
      controls. Infants with lethal congenital anomalies or who died in the delivery
      room were excluded. Data were collected from reviewing medical charts. RESULTS: A
      total of 34 inborn VLBW infants and 34 outborn VLBW infants with neonatal
      transport were included. Chronic lung disease (CLD) was significantly more
      frequent in the outborn group according to McNemar test (P = 0.0124) and logistic
      regression. Logistic regression also showed that outborn status (P = 0.0173) and
      birthweight (P = 0.0024) were the two most important risk factors for development
      of CLD. CONCLUSION: Well-trained short distance neonatal transport is useful and
      valuable for VLBW infants with gestation age of 27-34 weeks in Southern Taiwan.
      The respiratory outcome, however, was poor in the outborn group in terms of
      incidence of CLD. To improve the respiratory outcome, further modification of
      respiratory care during transportation or antenatal maternal transport is
      crucial.

PMID- 19405923
TI  - Eleven consecutive years of respiratory syncytial virus outbreaks in Croatia.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of severe
      lower respiratory tract infections (LRTI) in infants. The aim of the present
      study was to analyze the epidemiologic characteristics of RSV outbreaks in
      Croatian children. METHODS: Over a period of 11 consecutive years (1994-2005),
      3435 inpatients with acute respiratory infections (ARI) aged from birth to 10
      years and were residing in Zagreb County were tested for infection with RSV and
      other respiratory viruses at the Virology Department, Croatian National Institute
      of Public Health. RSV was identified in nasopharyngeal secretions by isolation on
      cell culture and/or detection with monoclonal antibodies using a direct
      fluorescence assay. RESULTS: RSV was the most common causative agent of ARI
      (42.2%; 658/1559) for the infants 0-6 months of age. It was also the etiologic
      agent of LRTI in 49% (495/1010) of infants of similar age. RSV was demonstrated
      in 56.5% (382/676) of infants with bronchiolitis, and in 36.5% (49/134) of those
      with pneumonia in this age group. CONCLUSION: The overall prevalence of RSV
      infection in Croatian children with acute respiratory illness, and its occurrence
      in various age groups, has remained stable over the past decade. RSV was found to
      be the most common cause of bronchiolitis occurring throughout childhood (52.7%;
      482/913).

PMID- 19405924
TI  - Toxocara seropositivity in Sri Lankan children with asthma.
AB  - BACKGROUND: Toxocariasis occurs in humans due to infection with Toxocara canis or
      T. cati, the nematode parasites of dogs and cats, respectively. The relationship
      between toxocariasis and asthma is complex, with some studies demonstrating that
      children with asthma were more likely to be Toxocara seropositive as compared to
      non-asthmatic children, and other studies indicating no such significant
      relationship. The aim of the present study was to investigate Toxocara
      seropositivity and its association with asthma in a selected group of Sri Lankan
      children. METHODS: Two groups of children were studied: group 1 included 100
      children with confirmed bronchial asthma who were on regular inhaler steroid
      treatment for asthma; group 2 included 96 children who did not have physician
      diagnosed asthma or upper respiratory tract infections, attending the same
      hospital. Diagnosis of Toxocara seropositivity was based on IgG Toxocara
      Microwell Serum Elisa Kits. Enzyme-linked immunosorbent assay was regarded as
      positive for a reading of 0.3 optical density units. Stool samples were examined
      for helminth ova. RESULTS: Toxocara seropositivity in children with asthma was
      29% and this was significantly more than Toxocara seropositivity among non
      asthmatic children (P < 0.001). Toxocara seropositivity was identified as a
      significant risk factor of asthma in a univariate model. Eosinophilia was seen in
      a significantly higher proportion of non-asthmatic and asthmatic children who
      were Toxocara seropositive. Toxocara seropositivity, however, was not identified
      as a significant risk factor in a multivariate model. CONCLUSIONS: The analysis
      confirmed previously identified risk factors for asthma but there was no
      association between the helminth parasitic infection, toxocariasis and bronchial
      asthma in children.

PMID- 19405925
TI  - Peritonitis rates and common microorganisms in continuous ambulatory peritoneal
      dialysis and automated peritoneal dialysis.
AB  - BACKGROUND: The aim of the present study was to perform a multicenter
      investigation in Turkish children on chronic peritoneal dialysis by examining the
      rates of peritonitis as well as causative organisms according to year. METHODS:
      Twelve pediatric renal units participated in this study and data were obtained by
      review of the medical records. RESULTS: One hundred and thirty-two patients were
      on continuous ambulatory peritoneal dialysis (CAPD), 21 were on automated
      peritoneal dialysis (APD) and 59 were on CAPD and APD at different times. Mean
      durations of CAPD and APD were 24.2 +/- 21.1 months and 22.9 +/- 12.8 months,
      respectively. Seventy-one (33%) out of 212 patients had no peritonitis episode.
      Overall peritonitis rate was one episode per 15.5 patient-months. The peritonitis
      rate was one episode per 15.4 patient-months for APD and one episode per 15.6
      patient-months for CAPD. Coagulase-negative staphylococcus was the most common
      cause of peritonitis among patients with positive culture (20.6%). While the
      incidence of Gram-negative infection remained unchanged according to year in
      patients on CAPD (P = 0.68), the rate of Gram-negative peritonitis in children on
      APD was significantly higher (P = 0.03). CONCLUSIONS: Peritonitis rate was
      similar in CAPD and APD, but the risk of Gram-negative peritonitis in APD was
      higher than that of CAPD.

PMID- 19405926
TI  - Thoracoscopic surgery in children in the Kyushu area of Japan.
AB  - BACKGROUND: Recently, minimally invasive thoracoscopic surgery has offered
      several options for both the diagnosis and surgical treatment in the field of
      pediatric surgery. This report reviews the surgical experience in order to assess
      the problems including the complications, encountered during thoracoscopic
      surgery in children under 15 years of age in the Kyushu area, Japan. METHODS:
      From 1993 to 2005, 153 boys and 103 girls underwent thoracoscopic surgery for
      chest disease. Pertinent information included number of operations for each year,
      sex, age, indication, treatment procedure, follow-up duration, cause of
      conversion to thoracotomy, method of treatment, and complication. RESULTS: There
      has gradually been an increase in the number of operations every year. These
      included procedures for funnel chest, n= 121; pneumothorax, n= 25; mediastinal
      tumor, n= 25; palmar hyperhydrosis, n= 23; neuroblastoma, n= 11; and cystic lung
      disease, n= 10. A large portion of the surgery was for patients under 1 year of
      age excluding neonates. Approximately half of the procedures were for the
      excision of a neuroblastoma. Approximately half of the patients older than 5
      years of age underwent Nuss procedure for funnel chest. Almost all of the
      pneumothorax and palmar hyperhydrosis surgery was for patients 14 or 15 years
      old. Three patients required a conversion to a standard thoracotomy. Six
      complications occurred. There was no mortality associated with the thoracoscopic
      surgical procedures. CONCLUSIONS: Thoracoscopy is a useful diagnostic and
      therapeutic tool for both infants and children. Various thoracoscopic complex
      procedures have been performed both safely and effectively.

PMID- 19405927
TI  - Characteristics of pediatric-onset spinal cord injury.
AB  - BACKGROUND: Although children rarely experience spinal cord injuries (SCI), those
      who do are subject to various lifelong disabilities and morbidities. The aim of
      the present study was to retrospectively assess the characteristics of pediatric
      onset SCI patients and their differences among age groups. METHODS: Clinical
      characteristics were compared in 48 patients who experienced SCI during childhood
      and adolescence and who underwent rehabilitation treatment. Clinical
      characteristics were compared in patients under 4 years old (group A), 4-12 years
      old (group B), and 13-18 years old (group C) at SCI onset. Radiological findings
      were compared in 20 patients who were examined on both plain radiograph and
      computed tomography. RESULTS: The overall male: female ratio was 3:2, with SCI
      due to non-traumatic causes more frequent overall. Of traumatic causes of SCI,
      vehicle accident was the most frequent. Of non-traumatic causes, congenital
      anomaly was most frequent in group A, but tumors became dominant as age
      increased. Overall, thoracic cord level of injury was most frequent. SCI without
      radiologic abnormalities (SCIWORA) was predominant in group A, but none was
      observed in group C. Spinal fractures with or without subluxation accounted for
      >60% of group C SCI. CONCLUSIONS: Non-traumatic, thoracic cord injury was
      frequent in the pediatric SCI population. SCIWORA was predominant in younger
      children.

PMID- 19405928
TI  - Are city population and the number of emergency medical facilities correlated?
AB  - BACKGROUND: The shortage of physicians is reported in the small cities in Japan,
      but the mal-distribution of physicians and emergency medical facilities has not
      been fully investigated. METHODS: Survey of Medical Institutions, 2005, Survey of
      Physicians, Dentists and Pharmacists, 2004, and 2005 Population Census of Japan
      were used. The relationships between city population and the numbers of medical
      resources such as emergency medical facilities, physicians and pediatricians were
      analyzed. RESULTS: The population and the number of emergency medical facilities
      of 895 cities were strongly correlated (r = 0.800, P = 0.000), and the numbers of
      the physicians and pediatricians had strong relationships to city population.
      CONCLUSION: All the cities cannot provide 24 h emergency services, therefore
      access time to medical facilities should be shortened by the construction of a
      transportation network instead of dispatching physicians to remote districts.

PMID- 19405929
TI  - Congenital cardiac malformations in neonates with apparently isolated
      gastrointestinal malformations.
AB  - BACKGROUND: The association of congenital cardiac malformations (CCM) with
      malformations of the gastrointestinal tract/abdominal wall is known.
      Nevertheless, the data presently available are derived from patient populations
      that include some special conditions known to be associated with a high rate of
      CCM. The aim of the present study was therefore to determine the incidence of
      cardiac malformations among neonates with apparently isolated malformations of
      the gastrointestinal tract/abdominal wall. METHODS: A total of 201 neonates with
      apparently isolated gastrointestinal malformations were screened on
      echocardiography. RESULT: Thirty-six (17.9%) of the neonates were diagnosed as
      having a CCM. When the four most frequent gastrointestinal malformations were
      evaluated, a CCM was diagnosed in 11/69 (15.9%) with anal atresia, in 9/38
      (23.7%) with tracheoesophageal fistula/esophageal atresia, in 2/25 (8%) with
      diaphragmatic hernia and in 5/17 (29.4%) with intestinal atresia. In 11 of 36
      patients (30.6%) with CCM, the cardiac problems were hemodynamically significant,
      requiring anti-congestive and/or surgical treatment. CONCLUSION: A significant
      number of neonates with apparently isolated gastrointestinal malformations had
      CCM. Because almost all patients with malformations of the gastrointestinal
      tract/abdominal wall require early surgical intervention, they should be
      evaluated on echocardiography to investigate CCM at the earliest opportunity.

PMID- 19405930
TI  - Cross-calibration of multi-frequency bioelectrical impedance analysis with eight
      point tactile electrodes and dual-energy X-ray absorptiometry for assessment of
      body composition in healthy children aged 6-18 years.
AB  - BACKGROUND: In diagnosis and treatment of obesity, body composition analysis
      including percent body fat (%BF) is useful in the clinical setting. Because
      bioelectrical impedance analysis (BIA) could be used quickly, easily and was non
      invasive in clinical setting, the purpose of the present study was to evaluate
      the usefulness of multi-frequency BIA with eight-point tactile electrodes (MF
      BIA8; InBody 720, Biospace) compared with dual-energy X-ray absorptiometry (DXA)
      in healthy children and adolescents. METHODS: A total of 166 children and
      adolescents under 18 (male, n = 86; female, n = 80) were recruited. Height,
      weight, body mass index (BMI) and Tanner stage were measured for each subject.
      The body composition such as fat-free mass (FFM), fat mass (FM), and %BF was
      measured on BIA and DXA and compared. RESULTS: On linear regression analysis, DXA
      FFM = 1.006(BIA FFM) + 0.554, R(2) = 0.99 and the standard error of the estimate
      (SEE) was 1.16 kg; DXA FM = 0.971(BIA FM) - 0.596, R(2) = 0.93; SEE, 1.34 kg; and
      DXA %BF = 0.940(BIA %BF) - 1.026, R(2) = 0.858; SEE, 3.03%. Limit of agreement in
      FFM, FM, and %BF was 0.7 +/- 2.3 kg, -0.9 +/- 2.9 kg and -2.2 +/- 6.1%,
      respectively. CONCLUSIONS: Although the %BF was not interchangeable with DXA, MF
      BIA8 (InBody 720; Biospace) could be used to measure body composition of children
      and adolescents in the clinical field because of its high precision.

PMID- 19405931
TI  - First-episode versus recurrent acute rheumatic fever: is it different?
AB  - BACKGROUND: Recurrent episodes of acute rheumatic fever (RF) can lead to
      rheumatic heart disease with considerable disability and mortality in children.
      RF can recur in the absence of secondary prophylaxis. The differences in clinical
      manifestations and outcome between first-episode and recurrent RF have been less
      studied. METHODS: A cross-section of patients under 14 years was studied for 2
      years (2003-2005) in order to compare the clinical, laboratory, echocardiographic
      profile and outcome of first-episode RF with recurrent attacks, and risk factors
      for recurrence and mortality. Patients without a previous history of RF and/or
      mitral stenosis (MS) and/or aortic stenosis (AS) were defined as first-episode
      patients, and patients with previous history of RF and/or MS and/or AS, were
      defined as recurrent RF patients based on the Jones criteria. RESULTS: Of 51
      patients in total, 26 had first-episode RF and 25 had recurrent RF. Arthritis
      occurred in a significantly higher number of first-episode patients (P = 0.047)
      whereas shortness of breath (SOB; P = 0.003), palpitation (P = 0.034), and aortic
      regurgitation (AR; P = 0.001) occurred in a significantly higher number of
      recurrent RF patients. Audible murmur of corresponding echocardiographic
      regurgitation was present in all recurrent RF patients whereas audible murmur was
      present in 61.5% and echocardiographic regurgitation in 81% in first-episode
      patients (P = 0.007). Palpitation, SOB, audible murmur, thrill, age and AR on
      admission were independent predictors of recurrence. Palpitation, age and AS on
      admission were independent predictors of mortality. CONCLUSIONS: Subclinical
      carditis occurred only in the first-episode patients, which requires further
      evaluation for clinical significance. Because all deaths occurred in recurrent RF
      group (P = 0.02), secondary prophylaxis and management of sore throat need re
      emphasis.

PMID- 19405932
TI  - Hypergalactosemia in early infancy: diagnostic strategy with an emphasis on
      imaging.
AB  - BACKGROUND: Portosystemic shunt is one of the main causes of persistent
      hypergalactosemia without enzyme deficiency, but the diagnostic imaging strategy
      has not yet been established. The purpose of the present study was to establish a
      diagnostic imaging strategy. METHODS: A retrospective investigation of the
      clinical and imaging findings of 10 children with persistent hypergalactosemia
      without enzyme deficiency detected by screening was undertaken. RESULTS: Abnormal
      ultrasonography (US) findings were detected in all eight patients with liver
      disorders. In three patients with citrin deficiency, the combination of fatty
      liver on US and laboratory evidence of cholestasis led to the diagnosis. In three
      patients with portosystemic shunt, US on sedation clearly depicted the shunt
      vessels. The extent was more easily understood on contrast computed tomography
      (CT). Per-rectal portal scintigraphy with N-isopropyl-p-I-123 iodoamphetamine and
      lung perfusion scintigraphy with (99m)Tc macroaggregated albumin were useful for
      evaluation of portal shunt index and assessment of pulmonary arteriovenous shunt.
      One patient underwent transarterial coil embolization. In two patients with
      hepatic tumor, the lesions and its vascularity were clearly demonstrated on US
      and dynamic CT. In one patient, small shunt index on per-rectal portal
      scintigraphy suggested no need for treatment. The other patient was treated with
      a combination of steroid, radiation, and interventional radiology. The etiology
      remained unknown in two children. CONCLUSIONS: In the assessment of
      hypergalactosemia, US is the modality of choice. CT is a useful tool for more
      detailed evaluation of the abnormalities found on US. Per-rectal portal
      scintigraphy and pulmonary perfusion scintigraphy play an important role in the
      evaluation of portosystemic shunt. Interventional radiology is sometimes
      effective.

PMID- 19405933
TI  - Intravenous luteinizing hormone-releasing hormone has no effect on serum N
      terminal pro-brain natriuretic peptide in children and adolescents.
AB  - BACKGROUND: Little is known about the acute effects of i.v. luteinizing hormone
      releasing hormone (LHRH) on the heart function, therefore the aim of the present
      study was to measure N-terminal pro-brain natriuretic peptide (N-BNP) in
      children, who underwent a diagnostic work up for short stature or delayed
      puberty. METHODS: N-BNP was measured in 52 children before and after
      administration of LHRH. Serum N-BNP obtained from 255 healthy children and
      adolescents (aged birth-18.3 years) served as a reference. RESULTS: There was no
      significant difference between baseline N-BNP of children who underwent the LHRH
      diagnostic test and their healthy peers. There was no significant serum N-BNP
      level change before or after administration of LHRH (59 +/- 36 pg/mL vs 58 +/- 34
      pg/mL). N-BNP fell from 399 +/- 425 pg/mL in newborns and reached 44 +/- 36 pg/mL
      in children aged 12-18 years. CONCLUSION: Short stature or delayed puberty had no
      effect on heart function determined by serum N-BNP; i.v. LHRH does not acutely
      influence the level of serum N-BNP.

PMID- 19405934
TI  - Serum pro-hepcidin levels in term and preterm newborns with sepsis.
AB  - BACKGROUND: An iron regulatory peptide hormone, hepcidin, is also part of the
      innate immune system and is strongly induced during infections and inflammation.
      The aim of the present study was to determine serum levels of the 60 aa pro
      hormone form of hepcidin (pro-hepcidin) in full-term and preterm newborns with
      sepsis and to determine the possible relationships between pro-hepcidin levels
      and serum iron and complete blood count parameters. METHODS: Fifteen preterm
      newborns with sepsis, 17 healthy preterm, six full-term newborns with sepsis and
      16 healthy full-term newborns were included the study. Blood samples were
      collected from patients with sepsis at the time of clinical diagnosis. Each blood
      sample was analyzed for complete blood count, serum iron and ferritin
      concentrations, iron-binding capacity, and pro-hepcidin level. RESULTS: The mean
      serum pro-hepcidin level (mean +/- SD) in preterm neonates with sepsis and in
      healthy preterm newborns was 565.4 +/- 519.5 ng/mL and 279.8 +/- 227.6 ng/mL,
      respectively (P < 0.05). The mean serum pro-hepcidin level in full-term newborns
      with sepsis and in healthy full-term neonates was 981.4 +/- 415.4 ng/mL and 482
      +/- 371.9 ng/mL, respectively (P < 0.05). Although the mean serum ferritin levels
      in the two groups with sepsis were higher when compared with the healthy groups,
      the difference was not statistically significant in full-term newborns. No
      statistically significant correlations were found between serum pro-hepcidin
      levels and any other parameters in each group. CONCLUSIONS: Serum pro-hepcidin
      levels were higher in newborns with sepsis (either premature or full-term) than
      they were in healthy newborns at the time of clinical diagnosis.

PMID- 19405935
TI  - Automated FingerPrint Background removal: FPB.
AB  - BACKGROUND: The construction of a whole-genome physical map has been an essential
      component of numerous genome projects initiated since the inception of the Human
      Genome Project. Its usefulness has been proved for whole-genome shotgun projects
      as a post-assembly validation and recently it has also been used in the assembly
      step to constrain on BACs positions. Fingerprinting is usually the method of
      choice for construction of physical maps. A clone fingerprint is composed of true
      peaks representing real fragments and background peaks, mainly composed of E.
      coli genomic DNA, partial digestions, star activity by-products, and machine
      background. High-throughput fingerprinting leads to the production of thousands
      of BAC clone fingerprints per day. That is why background peaks removal has
      become an important issue and needs to be automatized, especially in capillary
      electrophoresis based fingerprints. RESULTS: At the moment, the only tools
      available for such a task are GenoProfiler and its descendant FPMiner. The large
      variation in the quality of fingerprints that is usually present in large
      fingerprinting projects represents a major difficulty in the correct removal of
      background peaks that has only been partially addressed by the methods so far
      adopted that all require a long manual optimization of parameters. Thus, we
      implemented a new data-independent tool, FPB (FingerPrint Background removal),
      suitable for large scale projects as well as mapping of few clones. CONCLUSION:
      FPB is freely available at http://www.appliedgenomics.org/tools.php. FPB was used
      to remove the background from all fingerprints of three grapevine physical map
      projects. The first project consists of about 50,000 fingerprints, the second one
      consists of about 70,000 fingerprints, and the third one consists of about 45,000
      fingerprints. In all cases a successful assembly was built.

PMID- 19405936
TI  - Assessing quality of life in a randomized clinical trial: correcting for missing
      data.
AB  - BACKGROUND: Health-related quality of life is a topic of current interest. This
      paper considers a randomized phase III study of radiation therapy with concurrent
      chemotherapy (docetaxel) versus radiation therapy alone in non-small cell lung
      cancer, stage III A/B. Longitudinal data on quality of life have been obtained
      through repeated administration of a multi-item questionnaire (EORTC QLQ-C30)
      developed by the European Organisation for Research and Treatment of Cancer.
      Missingness in the data is owing to patients having failed to complete the
      questionnaire at some of the scheduled filling-in times. METHODS: We have
      analysed a monotone (in terms of missingness) subset of the data as regards
      estimation of the mean score of a summary measure of self-reported quality of
      life in a hypothetical drop-out-free population at different points in time.
      Missingness is a difficult issue of great importance. We have therefore chosen to
      compare three different methods that are relatively easy to implement: the linear
      increments method, the inverse-probability-weighting method and the Markov
      process method. Single imputation has been applied in a supplementary analysis to
      fill in for all the non-consecutive missing score values prior to the execution
      of the estimation procedure. RESULTS: For the response in focus, the observed
      mean score at a certain time is larger than the estimated mean scores, which
      implies that the true mean score is easily overestimated unless the missingness
      is appropriately adjusted for. Comparison of the treatment arms shows a
      significant difference in mean score at the end of treatment. CONCLUSION: Use of
      proper methodology developed for analysing data subject to missingness is
      necessary to reduce potential estimation bias. The quality of life of patients
      receiving radiation therapy with concurrent chemotherapy (docetaxel) appears
      somewhat worse than that of patients receiving radiation therapy alone in the
      period during which treatment is given. The conclusions are robust for the choice
      of statistical methods.

PMID- 19405937
TI  - Cardiovascular magnetics resonance diagnosis of cystic tumor of the
      atrioventricular node.
AB  - Late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) has proven
      to be the gold standard for viability assessment. LGE CMR is also useful for
      identifying the nature of cardiac masses or lesions. We report a case of a rare
      primary cystic tumor of the atrioventricular node, in which CMR proved to be
      valuable.

PMID- 19405938
TI  - Outcomes and factors influencing survival in cirrhotic cases with spontaneous
      rupture of hepatocellular carcinoma: a multicenter study.
AB  - BACKGROUND: Spontaneous rupture is rare complication of hepatocellular carcinoma
      (HCC) with high mortality rate in cirrhotic cases. The aim of this study was to
      determine the factors influencing prognosis in cases of spontaneously ruptured
      HCC and to investigate the outcomes of the treatments employed, especially
      transcatheter arterial embolization (TAE). METHODS: A retrospective multicenter
      study was conducted in 48 cirrhotic patients with spontaneous rupture of HCC.
      Conservative treatment was employed in 32 patients (ConT group) and TAE was
      performed in 16 patients (TAE group). RESULTS: The median survival time (MST) in
      the ConT group was only 13.1 days and the survival rate was extremely poor: 59.4%
      at 7 days, 37.5% at 14 days, and 6.3% at 30 days. On the other hand, the MST in
      the TAE group was 244.8 days and the survival rate was 87.5% at 1 month, 56.3% at
      3 months, 23.4% at 12 months, and 15.6% at 24 months. According to the results of
      univariate analyses, factors associated with poor hepatic function and poor
      suitability for TAE was important determinants of short-term death (less than 3
      weeks) among the patients (p < 0.05). On the other hand, among the patients in
      whom initial TAE was successfully performed (n = 15), a multivariate analysis
      showed that a maximum tumor size not exceeding 7 cm was the only independent
      factor determining long-term survival (p = 0.0130). CONCLUSION: Despite the
      inherent limitations of this retrospective study, TAE appears to be a useful
      treatment strategy for cirrhotic patients with spontaneous HCC rupture, as it
      yielded a longer survival period compared with conservative treatment in patients
      with ruptured HCC. Among the patients with ruptured HCC in whom initial TAE was
      successfully performed, the maximum tumor size was an important factor
      influencing survival.

PMID- 19405939
TI  - Bos taurus genome sequence reveals the assortment of immunoglobulin and surrogate
      light chain genes in domestic cattle.
AB  - BACKGROUND: The assortment of cattle immunoglobulin and surrogate light chain
      genes has been extracted from the version 3.1 of Bos taurus genome sequence as a
      part of an international effort to sequence and annotate the bovine genome.
      RESULTS: 63 variable lambda chain and 22 variable kappa chain genes were
      identified and phylogenetically assigned to 8 and 4 subgroups, respectively. The
      specified phylogenetic relationships are compatible with the established ruminant
      light chain variable gene families or subgroups. Because of gaps and
      uncertainties in the assembled genome sequence, the number of genes might change
      in the future versions of the genome sequence. In addition, three bovine
      surrogate light chain genes were identified. The corresponding cDNAs were cloned
      and the expression of the surrogate light chain genes was demonstrated from fetal
      material. CONCLUSION: The bovine kappa gene locus is compact and simple which may
      reflect the preferential use of the lambda chain in cattle. The relative
      orientation of variable and joining genes in both loci are consistent with a
      deletion mechanism in VJ joining. The orientation of some variable genes cannot
      be determined from the data available. The number of functional variable genes is
      moderate when compared to man or mouse. Thus, post-recombinatorial mechanisms
      might contribute to the generation of the bovine pre-immune antibody repertoire.
      The heavy chains probably contribute more to recombinational immunoglobulin
      repertoire diversity than the light chains but the heavy chain locus could not be
      annotated from the version 3.1 of Bos taurus genome.

PMID- 19405940
TI  - In silico miRNA prediction in metazoan genomes: balancing between sensitivity and
      specificity.
AB  - BACKGROUND: MicroRNAs (miRNAs), short approximately 21-nucleotide RNA molecules,
      play an important role in post-transcriptional regulation of gene expression. The
      number of known miRNA hairpins registered in the miRBase database is rapidly
      increasing, but recent reports suggest that many miRNAs with restricted temporal
      or tissue-specific expression remain undiscovered. Various strategies for in
      silico miRNA identification have been proposed to facilitate miRNA discovery.
      Notably support vector machine (SVM) methods have recently gained popularity.
      However, a drawback of these methods is that they do not provide insight into the
      biological properties of miRNA sequences. RESULTS: We here propose a new strategy
      for miRNA hairpin prediction in which the likelihood that a genomic hairpin is a
      true miRNA hairpin is evaluated based on statistical distributions of observed
      biological variation of properties (descriptors) of known miRNA hairpins. These
      distributions are transformed into a single and continuous outcome classifier
      called the L score. Using a dataset of known miRNA hairpins from the miRBase
      database and an exhaustive set of genomic hairpins identified in the genome of
      Caenorhabditis elegans, a subset of 18 most informative descriptors was selected
      after detailed analysis of correlation among and discriminative power of
      individual descriptors. We show that the majority of previously identified miRNA
      hairpins have high L scores, that the method outperforms miRNA prediction by
      threshold filtering and that it is more transparent than SVM classifiers.
      CONCLUSION: The L score is applicable as a prediction classifier with high
      sensitivity for novel miRNA hairpins. The L-score approach can be used to rank
      and select interesting miRNA hairpin candidates for downstream experimental
      analysis when coupled to a genome-wide set of in silico-identified hairpins or to
      facilitate the analysis of large sets of putative miRNA hairpin loci obtained in
      deep-sequencing efforts of small RNAs. Moreover, the in-depth analyses of miRNA
      hairpins descriptors preceding and determining the L score outcome could be used
      as an extension to miRBase entries to help increase the reliability and
      biological relevance of the miRNA registry.

PMID- 19405941
TI  - Identification of differentially expressed subnetworks based on multivariate
      ANOVA.
AB  - BACKGROUND: Since high-throughput protein-protein interaction (PPI) data has
      recently become available for humans, there has been a growing interest in
      combining PPI data with other genome-wide data. In particular, the identification
      of phenotype-related PPI subnetworks using gene expression data has been of great
      concern. Successful integration for the identification of significant subnetworks
      requires the use of a search algorithm with a proper scoring method. Here we
      propose a multivariate analysis of variance (MANOVA)-based scoring method with a
      greedy search for identifying differentially expressed PPI subnetworks. RESULTS:
      Given the MANOVA-based scoring method, we performed a greedy search to identify
      the subnetworks with the maximum scores in the PPI network. Our approach was
      successfully applied to human microarray datasets. Each identified subnetwork was
      annotated with the Gene Ontology (GO) term, resulting in the phenotype-related
      functional pathway or complex. We also compared these results with those of other
      scoring methods such as t statistic- and mutual information-based scoring
      methods. The MANOVA-based method produced subnetworks with a larger number of
      proteins than the other methods. Furthermore, the subnetworks identified by the
      MANOVA-based method tended to consist of highly correlated proteins. CONCLUSION:
      This article proposes a MANOVA-based scoring method to combine PPI data with
      expression data using a greedy search. This method is recommended for the highly
      sensitive detection of large subnetworks.

PMID- 19405942
TI  - Detection of serum MMP-7 and MMP-9 in cholangiocarcinoma patients: evaluation of
      diagnostic accuracy.
AB  - BACKGROUND: Cholangiocarcinoma is an aggressive tumor with a tendency for local
      invasion and distant metastases. Timely diagnosis is very important because
      surgical resection (R0) remains the only hope for a cure. However, at present,
      there is no available tumor marker that can differentiate cholangiocarcinoma from
      benign bile duct disease. Previous studies have demonstrated that matrix
      metalloproteinase (MMP)-7 and MMP-9 are frequently expressed in
      cholangiocarcinoma specimens. METHODS: This study was designed to determine
      whether the serum levels of MMP-7 and MMP-9 can discriminate cholangiocarcinoma
      patients from benign biliary tract disease patients in comparison to
      carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). We
      measured the level of CEA, CA19-9, MMP-7 and MMP-9 in the serum of 44
      cholangiocarcinoma and 36 benign biliary tract diseases patients. RESULTS: Among
      the serum levels of CEA, CA19-9, MMP-7 and MMP-9, only the serum MMP-7 level was
      significantly higher in the patients with cholangiocarcinoma (8.9 +/- 3.43 ng/ml)
      compared to benign biliary tract disease patients (5.9 +/- 3.03 ng/ml) (p <
      0.001). An receiver operating characteristic (ROC) curve analysis revealed that
      the detection of the serum MMP-7 level is reasonably accurate in differentiating
      cholangiocarcinoma from benign biliary tract disease patients (area under curve =
      0.73; 95% CI = 0.614-0.848). While the areas under the curve of the ROC curves
      for CEA, CA19-9 and MMP-9 were 0.63 (95% CI = 0.501-0.760), 0.63 (95% CI = 0.491
      0.761) and 0.59 (95% CI = 0.455-0.722), respectively. CONCLUSION: Serum MMP-7
      appears to be a valuable diagnostic marker in the discrimination of
      cholangiocarcinoma from benign biliary tract disease. Further prospective studies
      for serum MMP-7 measurement should be carried out to further investigate the
      potential of this molecule as a biomarker of cholangiocarcinoma.

PMID- 19405943
TI  - Transient effect of weak electromagnetic fields on calcium ion concentration in
      Arabidopsis thaliana.
AB  - BACKGROUND: Weak magnetic and electromagnetic fields can influence physiological
      processes in animals, plants and microorganisms, but the underlying way of
      perception is poorly understood. The ion cyclotron resonance is one of the
      discussed mechanisms, predicting biological effects for definite frequencies and
      intensities of electromagnetic fields possibly by affecting the physiological
      availability of small ions. Above all an influence on Calcium, which is crucial
      for many life processes, is in the focus of interest. We show that in Arabidopsis
      thaliana, changes in Ca2+-concentrations can be induced by combinations of
      magnetic and electromagnetic fields that match Ca2+-ion cyclotron resonance
      conditions. RESULTS: An aequorin expressing Arabidopsis thaliana mutant (Col0-1
      Aeq Cy+) was subjected to a magnetic field around 65 microtesla (0.65 Gauss) and
      an electromagnetic field with the corresponding Ca2+ cyclotron frequency of 50
      Hz. The resulting changes in free Ca2+ were monitored by aequorin
      bioluminescence, using a high sensitive photomultiplier unit. The experiments
      were referenced by the additional use of wild type plants. Transient increases of
      cytosolic Ca2+ were observed both after switching the electromagnetic field on
      and off, with the latter effect decreasing with increasing duration of the
      electromagnetic impact. Compared with this the uninfluenced long-term loss of
      bioluminescence activity without any exogenic impact was negligible. The magnetic
      field effect rapidly decreased if ion cyclotron resonance conditions were
      mismatched by varying the magnetic fieldstrength, also a dependence on the
      amplitude of the electromagnetic component was seen. CONCLUSION: Considering the
      various functions of Ca2+ as a second messenger in plants, this mechanism may be
      relevant for perception of these combined fields. The applicability of recently
      hypothesized mechanisms for the ion cyclotron resonance effect in biological
      systems is discussed considering it's operating at magnetic field strengths weak
      enough, to occur occasionally in our all day environment.

PMID- 19405944
TI  - Elevation of Bombina variegata peptide 8 in mice with collagen-induced arthritis.
AB  - BACKGROUND: Bombina variegate peptide 8 (Bv8) is a small protein secreted by frog
      skin. Recently it has been shown to contribute to tumor angiogenesis in mouse
      model. The purpose of this study was to investigate Bv8 in mice with type II
      collagen-induced arthritis (CIA). METHODS: We induced CIA in male DBA/1J mice.
      The severity of arthritis was evaluated based on an arthritis score. RNA was
      extracted from the joint, and examined for Bv8 mRNA expression by RT-PCR and real
      time RT-PCR. Synovial tissue and bone marrow were immunohistochemically examined
      using anti-Bv8 antibody. RESULTS: The level of Bv8 mRNA expression in the joint
      was below the detection limit in the control group, but was elevated in the CIA
      group, and was correlated with the arthritis score. In addition, an increase in
      Bv8-positive cells was observed in the synovium and bone marrow in the CIA group.
      CONCLUSION: Bv8 was elevated in the synovium and bone marrow of CIA mice,
      suggesting that Bv8 plays an important role in the pathogenesis of arthritis.

PMID- 19405946
TI  - Visceral leishmaniasis with cardiac involvement in a dog: a case report.
AB  - A dog presented with cutaneous nodules, enlarged lymph nodes and oedema in limbs,
      face and abdomen. The diagnosis of visceral leishmaniasis was established by
      identification of Leishmania amastigotes within macrophages from skin and
      popliteal lymph node biopsies. At necropsy, lesions were found in different
      organs, but it was particularly striking to observe large areas of pallor in the
      myocardium. Histological examination revealed an intense chronic inflammatory
      reaction in many organs, and numerous macrophages were found to contain
      amastigote forms of Leishmania. The inflammatory reaction was especially severe
      in the heart, where large areas of the myocardium appeared infiltrated with huge
      numbers of mononuclear immune cells, causing cardiac muscle atrophy and
      degeneration. Despite the severe inflammation, the number of parasitized
      macrophages was low in the myocardium, as revealed by immunohistochemical
      staining of Leishmania amastigotes. Because cardiac involvement is not usually
      described in this condition, this dog represents a very rare case of canine
      visceral leishmaniasis with affection of the myocardium.

PMID- 19405945
TI  - Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are
      strongly prognostic in luminal breast cancer.
AB  - INTRODUCTION: Breast cancers are traditionally divided into hormone-receptor
      positive and negative cases. This classification helps to guide patient
      management. However, a subgroup of hormone-receptor positive patients relapse
      irrespective of hormonal therapy. Gene expression profiling has classified breast
      tumours into five major subtypes with significant different outcome. The two
      luminal subtypes, A and B, show high expression of ESR1, GATA3 and FOXA1 genes.
      Prognostic biomarkers for oestrogen receptor (ER)-positive cases include
      progesterone receptor (PR) and androgen receptor (AR), and proteins related to
      proliferation or apoptotic resistance. The aim of this study was to identify the
      best predictors of success of hormonal therapy. METHODS: By immunohistochemistry
      we studied 10 markers in a consecutive series of 832 cases of breast carcinoma
      treated at the Paoli-Calmettes Institute from 1990 to 2002 and deposited onto
      tissue microarrays (TMA). These markers were luminal-related markers ER, PR, AR,
      FOXA1 and GATA3 transcription factors, proliferation-related Ki67 and CCND1,
      ERBB2, anti-apoptotic BCL2 and P53. We also measured vascular peritumoural
      invasion (VPI), size, grade and lymph node involvement. For 143 cases, gene
      expression profiles were available. Adjuvant chemotherapy and hormonal therapy
      were given to high- and low-risk patients, respectively. The 162 events observed
      and taken into account were metastases. RESULTS: Molecular expression of the 10
      parameters and subtype with ER status were strongly correlated. Of the 67 luminal
      A cases of this series, 63 were ER-positive. Multivariate analyses showed the
      highly significant prognostic value of VPI (hazard ratio (HR) = 2.47), Ki67 (HR =
      2.9), P53 (HR = 2.9) and GATA3 (HR = 0.5) for the 240 patients who received
      hormonal therapy. CONCLUSIONS: A panel of three antibodies (Ki67, P53 and GATA3)
      associated with VPI can significantly improve the traditional prognosticators in
      predicting outcome for ER-positive breast cancer patients receiving hormonal
      therapy.

PMID- 19405948
TI  - Economic burden of cholera in the WHO African region.
AB  - BACKGROUND: In 2007, various countries around the world notified 178677 cases of
      cholera and 4033 cholera deaths to the World Health Organization (WHO). About 62%
      of those cases and 56.7% of deaths were reported from the WHO African Region
      alone. To date, no study has been undertaken in the Region to estimate the
      economic burden of cholera for use in advocacy for its prevention and control.
      The objective of this study was to estimate the direct and indirect cost of
      cholera in the WHO African Region. METHODS: Drawing information from various
      secondary sources, this study used standard cost-of-illness methods to estimate:
      (a) the direct costs, i.e. those borne by the health-care system and the family
      in directly addressing cholera; and (b) the indirect costs, i.e. loss of
      productivity caused by cholera, which is borne by the individual, the family or
      the employer. The study was based on the number of cholera cases and deaths
      notified to the World Health Organization by countries of the WHO African Region.
      RESULTS: The 125018 cases of cholera notified to WHO by countries of the African
      Region in 2005 resulted in a real total economic loss of US$39 million, US$ 53.2
      million and US$64.2 million, assuming a regional life expectancies of 40, 53 and
      73 years respectively. The 203,564 cases of cholera notified in 2006 led to a
      total economic loss US$91.9 million, US$128.1 million and US$156 million,
      assuming life expectancies of 40, 53 and 73 years respectively. The 110,837 cases
      of cholera notified in 2007 resulted in an economic loss of US$43.3 million,
      US$60 million and US$72.7 million, assuming life expectancies of 40, 53 and 73
      years respectively. CONCLUSION: There is an urgent need for further research to
      determine the national-level economic burden of cholera, disaggregated by
      different productive and social sectors and occupations of patients and
      relatives, and national-level costs and effectiveness of alternative ways of
      scaling up population coverage of potable water and clean sanitation facilities.

PMID- 19405947
TI  - Development of a novel small antibody that retains specificity for tumor
      targeting.
AB  - BACKGROUND: For the targeted therapy of solid tumor mediated by monoclonal
      antibody (mAb), there have different models of rebuilding small antibodies
      originated from native ones. Almost all natural antibody molecules have the
      similar structure and conformation, but those rebuilt small antibodies cannot
      completely keep the original traits of parental antibodies, especially the
      reduced specificity, which gravely influences the efficacy of small antibodies.
      METHODS: In this study, authors developed a novel mimetic in the form of
      V(H)FR1(C-10-)V(H)CDR1-V(H)FR2-V(L)CDR3-V(L)FR4(N-10) for a parental mAb induced
      with human breast cancer, and the mimetic moiety was conjugated to the C-terminal
      of toxicin colicin Ia. The novel fusion peptide, named protomimecin (PMN), was
      administered to MCF-7 breast cancer cells to demonstrate its killing competency
      in vitro and in vivo. RESULTS: Compared with original antibody-colicin Ia (Fab
      Ia) and single-chain antibody-colicin Ia (Sc-Ia) fusion proteins, PMN retained
      the targeting specificity of parental antibody and could specifically kill MCF-7
      cells in vitro. By injecting intraperitoneally into BALB/c athymic mice bearing
      MCF-7 tumors, with reduced affinity, PMN significantly suppressed the growth of
      tumors compared with control mice treated by toxicin protein, Fab-Ia protein, Sc
      Ia protein or by PBS (p < 0.05). CONCLUSION: This novel mimetic antibody retained
      original specificity of parental antibody, and could effectively guide killer
      moiety to suppress the growth of breast cancer by targeted cell death.

PMID- 19405949
TI  - Structure-Function analysis of the CTLA-4 interaction with PP2A.
AB  - BACKGROUND: CTLA-4 functions primarily as an inhibitor of T cell activation.
      There are several candidate explanations as to how CTLA-4 modulates T cell
      responses, but the exact mechanism remains undefined. The tail of CTLA-4 does not
      have any intrinsic enzymatic activity but is able to associate with several
      signaling molecules including the serine/threonine phosphatase PP2A. PP2A is a
      heterotrimeric molecule comprised of a regulatory B subunit associated with a
      core dimer of a scaffolding (A) and a catalytic (C) subunit. RESULTS: Here, we
      performed an analysis of the human CTLA-4 interface interacting with PP2A. We
      show that PP2A interacts with the cytoplasmic tail of CTLA-4 in two different
      sites, one on the lysine rich motif, and the other on the tyrosine residue
      located at position 182 (but not the tyrosine 165 of the YVKM motif). Although
      the interaction between CTLA-4 and PP2A was not required for inhibition of T cell
      responses, it was important for T cell activation by inverse agonists of CTLA-4.
      Such an interaction was functionally relevant because the inverse agonists
      induced IL-2 production in an okadaic acid-dependent manner. CONCLUSION: Our
      studies demonstrate that PP2A interacts with the cytoplasmic tail of human CTLA-4
      through two motifs, the lysine rich motif centered at lysine 155 and the tyrosine
      residue 182. This interaction and the phosphatase activity of PP2A are important
      for CTLA-4-mediated T cell activation.

PMID- 19405950
TI  - Further validation of the Health Scale of Traditional Chinese Medicine (HSTCM).
AB  - BACKGROUND: Few health measurement scales are based on Chinese medicine theory.
      The Health Scale of Traditional Chinese Medicine (HSTCM) was developed to fill
      this gap. The aim of this study is to validate the HSTCM. METHODS: A convenience
      sample of 630 participants was recruited in 11 settings. All participants were
      asked to complete the HSTCM and World Health Organization Quality of Life Measure
      Abbreviated Version (WHOQOL-BREF). RESULTS: Properties of the HSTCM were tested.
      Intra-class correlation coefficient representing the inter-interviewer
      reliability was 0.99 (95%CI) for the overall instrument. Spearman-Brown
      correlation coefficient and Cronbach's coefficient alpha were 0.81 and 0.94
      respectively, indicating satisfactory internal reliability and inter-interviewer
      reliability. Spearman's rho correlation coefficient between the HSTCM and WHOQOL
      BREFF was -0.67. A receiver operating characteristic (ROC) curve analysis was
      performed to test the discriminate validation. Areas under the ROC curve analysis
      for the HSTCM and its domains ranged 0.71-0.87 and all the lower levels of 95%CI
      were greater than 0.50. CONCLUSION: The HSTCM was validated as a generic health
      scale and may complement existing health measurement scales in Chinese medicine
      health care.

PMID- 19405951
TI  - RANKL increases the level of Mcl-1 in osteoclasts and reduces bisphosphonate
      induced osteoclast apoptosis in vitro.
AB  - INTRODUCTION: Bisphosphonates are the most widely used class of drug for
      inhibiting osteoclast-mediated bone loss, but their effectiveness at preventing
      joint destruction in rheumatoid arthritis has generally been disappointing. We
      examined whether the ability of bisphosphonates to induce osteoclast apoptosis
      and inhibit bone resorption in vitro is influenced by the cytokine receptor
      activator of nuclear factor-kappa B ligand (RANKL), an important mediator of
      inflammation-induced bone loss. METHODS: Rabbit osteoclasts were treated with the
      bisphosphonates clodronate or alendronate for up to 48 hours in the absence or
      presence of RANKL. Changes in cell morphology and induction of apoptosis were
      examined by scanning electron microscopy, whilst resorptive activity was
      determined by measuring the area of resorption cavities. Changes in the level of
      anti-apoptotic proteins, including Mcl-1, Bcl-2, and Bcl-x>L, were determined in
      rabbit osteoclasts and in cytokine-starved mouse osteoclasts by Western blotting.
      RESULTS: RANKL significantly attenuated the ability of both clodronate and
      alendronate to induce osteoclast apoptosis and inhibit bone resorption. Treatment
      of rabbit osteoclasts with RANKL was associated with an increase in the anti
      apoptotic protein Mcl-1 but not Bcl-2. A role for Mcl-1 in osteoclast survival
      was suggested using osteoclasts generated from mouse bone marrow macrophages in
      the presence of RANKL + macrophage colony-stimulating factor (M-CSF) since
      cytokine deprivation of mouse osteoclasts caused a rapid loss of Mcl-1 (but not
      Bcl-2 or Bcl-xL), which preceded the biochemical and morphological changes
      associated with apoptosis. Loss of Mcl-1 from mouse osteoclasts could be
      prevented by factors known to promote osteoclast survival (RANKL, M-CSF, tumour
      necrosis factor-alpha [TNF-alpha], or lipopolysaccharide [LPS]). CONCLUSIONS:
      RANKL protects osteoclasts from the apoptosis-inducing and anti-resorptive
      effects of bisphosphonates in vitro. The ability of RANKL (and other pro
      inflammatory factors such as TNF-alpha and LPS) to increase the level of Mcl-1 in
      osteoclasts may explain the lack of effectiveness of some bisphosphonates in
      preventing inflammation-induced bone loss.

PMID- 19405953
TI  - Proteome analysis of schizophrenia patients Wernicke's area reveals an energy
      metabolism dysregulation.
AB  - BACKGROUND: Schizophrenia is likely to be a consequence of DNA alterations that,
      together with environmental factors, will lead to protein expression differences
      and the ultimate establishment of the illness. The superior temporal gyrus is
      implicated in schizophrenia and executes functions such as the processing of
      speech, language skills and sound processing. METHODS: We performed an individual
      comparative proteome analysis using two-dimensional gel electrophoresis of 9
      schizophrenia and 6 healthy control patients' left posterior superior temporal
      gyrus (Wernicke's area - BA22p) identifying by mass spectrometry several protein
      expression alterations that could be related to the disease. RESULTS: Our
      analysis revealed 11 downregulated and 14 upregulated proteins, most of them
      related to energy metabolism. Whereas many of the identified proteins have been
      previously implicated in schizophrenia, such as fructose-bisphosphate aldolase C,
      creatine kinase and neuron-specific enolase, new putative disease markers were
      also identified such as dihydrolipoyl dehydrogenase, tropomyosin 3, breast cancer
      metastasis-suppressor 1, heterogeneous nuclear ribonucleoproteins C1/C2 and
      phosphate carrier protein, mitochondrial precursor. Besides, the differential
      expression of peroxiredoxin 6 (PRDX6) and glial fibrillary acidic protein (GFAP)
      were confirmed by western blot in schizophrenia prefrontal cortex. CONCLUSION:
      Our data supports a dysregulation of energy metabolism in schizophrenia as well
      as suggests new markers that may contribute to a better understanding of this
      complex disease.

PMID- 19405952
TI  - Apigenin, a non-mutagenic dietary flavonoid, suppresses lupus by inhibiting
      autoantigen presentation for expansion of autoreactive Th1 and Th17 cells.
AB  - INTRODUCTION: Lupus patients need alternatives to steroids and cytotoxic drugs.
      We recently found that apigenin, a non-mutagenic dietary flavonoid, can sensitize
      recurrently activated, normal human T cells to apoptosis by inhibiting nuclear
      factor-kappa-B (NF-kappaB)-regulated Bcl-xL, cyclooxygenase 2 (COX-2), and
      cellular FLICE-like inhibitory protein (c-FLIP) expression. Because sustained
      immune activation and hyperexpression of COX-2 and c-FLIP contribute to lupus, we
      treated SNF1 mice that spontaneously develop human lupus-like disease with
      apigenin. METHODS: SNF1 mice with established lupus-like disease were injected
      with 20 mg/kg of apigenin daily and then monitored for development of severe
      nephritis. Histopathologic changes in kidneys, IgG autoantibodies to nuclear
      autoantigens in serum and in cultures of splenocytes, along with nucleosome
      specific T helper 1 (Th1) and Th17 responses, COX-2 expression, and apoptosis of
      lupus immune cells were analyzed after apigenin treatment. RESULTS: Apigenin in
      culture suppressed responses of Th1 and Th17 cells to major lupus autoantigen
      (nucleosomes) up to 98% and 92%, respectively, and inhibited the ability of lupus
      B cells to produce IgG class-switched anti-nuclear autoantibodies helped by these
      Th cells in presence of nucleosomes by up to 82%. Apigenin therapy of SNF1 mice
      with established lupus suppressed serum levels of pathogenic autoantibodies to
      nuclear antigens up to 97% and markedly delayed development of severe
      glomerulonephritis. Apigenin downregulated COX-2 expression in lupus T cells, B
      cells, and antigen-presenting cells (APCs) and caused their apoptosis.
      Autoantigen presentation and Th17-inducing cytokine production by dendritic cells
      were more sensitive to the inhibitory effect of apigenin in culture, as evident
      at 0.3 to 3 muM, compared with concentrations (10 to 100 microM) required for
      inducing apoptosis. CONCLUSIONS: Apigenin inhibits autoantigen-presenting and
      stimulatory functions of APCs necessary for the activation and expansion of
      autoreactive Th1 and Th17 cells and B cells in lupus. Apigenin also causes
      apoptosis of hyperactive lupus APCs and T and B cells, probably by inhibiting
      expression of NF-kappaB-regulated anti-apoptotic molecules, especially COX-2 and
      c-FLIP, which are persistently hyperexpressed by lupus immune cells. Increasing
      the bioavailability of dietary plant-derived COX-2 and NF-kappaB inhibitors, such
      as apigenin, could be valuable for suppressing inflammation in lupus and other
      Th17-mediated diseases like rheumatoid arthritis, Crohn disease, and psoriasis
      and in prevention of inflammation-based tumors overexpressing COX-2 (colon,
      breast).

PMID- 19405955
TI  - Comparative toxicity of 24 manufactured nanoparticles in human alveolar
      epithelial and macrophage cell lines.
AB  - BACKGROUND: A critical issue with nanomaterials is the clear understanding of
      their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of
      similar equivalent spherical diameter and various elemental compositions on 2
      human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a
      generic experimental set-up that would allow the rapid screening of cytotoxic
      effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and
      Neutral Red) and analyzed 2 time points (3 and 24 hours) for each cell type and
      nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle
      concentration inducing 50% cell mortality) was calculated. RESULTS: The use of
      MTT assay on THP-1 cells exposed for 24 hours appears to be the most sensitive
      experimental design to assess the cytotoxic effect of one nanoparticle. With this
      experimental set-up, Copper- and Zinc-based nanoparticles appear to be the most
      toxic. Titania, Alumina, Ceria and Zirconia-based nanoparticles show moderate
      toxicity, and no toxicity was observed for Tungsten Carbide. No correlation
      between cytotoxicity and equivalent spherical diameter or specific surface area
      was found. CONCLUSION: Our study clearly highlights the difference of sensitivity
      between cell types and cytotoxicity assays that has to be carefully taken into
      account when assessing nanoparticles toxicity.

PMID- 19405954
TI  - The effects of high frequency subthalamic stimulation on balance performance and
      fear of falling in patients with Parkinson's disease.
AB  - BACKGROUND: Balance impairment is one of the most distressing symptoms in
      Parkinson's disease (PD) even with pharmacological treatment (levodopa). A
      complementary treatment is high frequency stimulation in the subthalamic nucleus
      (STN). Whether STN stimulation improves postural control is under debate. The aim
      of this study was to explore the effects of STN stimulation alone on balance
      performance as assessed with clinical performance tests, subjective ratings of
      fear of falling and posturography. METHODS: Ten patients (median age 66, range 59
      69 years) with bilateral STN stimulation for a minimum of one year, had their
      anti-PD medications withdrawn overnight. Assessments were done both with the STN
      stimulation turned OFF and ON (start randomized). In both test conditions, the
      following were assessed: motor symptoms (descriptive purposes), clinical
      performance tests, fear of falling ratings, and posturography with and without
      vibratory proprioceptive disturbance. RESULTS: STN stimulation alone
      significantly (p = 0.002) increased the scores of the Berg balance scale, and the
      median increase was 6 points. The results of all timed performance tests, except
      for sharpened Romberg, were significantly (p <or= 0.016) improved. The patients
      rated their fear of falling as less severe, and the total score of the Falls
      Efficacy Scale(S) increased (p = 0.002) in median with 54 points. All patients
      completed posturography when the STN stimulation was turned ON, but three
      patients were unable to do so when it was turned OFF. The seven patients with
      complete data showed no statistical significant difference (p values >or= 0.109)
      in torque variance values when comparing the two test situations. This applied
      both during quiet stance and during the periods with vibratory stimulation, and
      it was irrespective of visual input and sway direction. CONCLUSION: In this
      sample, STN stimulation alone significantly improved the results of the clinical
      performance tests that mimic activities in daily living. This improvement was
      further supported by the patients' ratings of fear of falling, which were less
      severe with the STN stimulation turned ON. Posturography could not be performed
      by three out of the ten patients when the stimulation was turned OFF. The
      posturography results of the seven patients with complete data showed no
      significant differences due to STN stimulation.

PMID- 19405956
TI  - Comparison of strategies for substantiating freedom from scrapie in a sheep
      flock.
AB  - BACKGROUND: The public health threat represented by a potential circulation of
      bovine spongiform encephalopathy agent in sheep population has led European
      animal health authorities to launch large screening and genetic selection
      programmes. If demonstrated, such a circulation would have dramatic economic
      consequences for sheep breeding sector. In this context, it is important to
      evaluate the feasibility of qualification procedures that would allow sheep
      breeders demonstrating their flock is free from scrapie. Classical approaches,
      based on surveys designed to detect disease presence, do not account for scrapie
      specificities: the genetic variations of susceptibility and the absence of live
      diagnostic test routinely available. Adapting these approaches leads to a
      paradoxical situation in which a greater amount of testing is needed to
      substantiate disease freedom in genetically resistant flocks than in susceptible
      flocks, whereas probability of disease freedom is a priori higher in the former
      than in the latter. The goal of this study was to propose, evaluate and compare
      several qualification strategies for demonstrating a flock is free from scrapie.
      RESULTS: A probabilistic framework was defined that accounts for scrapie
      specificities and allows solving the preceding paradox. Six qualification
      strategies were defined that combine genotyping data, diagnostic tests results
      and flock pedigree. These were compared in two types of simulated flocks:
      resistant and susceptible flocks. Two strategies allowed demonstrating disease
      freedom in several years, for the majority of simulated flocks: a strategy in
      which all the flock animals are genotyped, and a strategy in which only founders
      animals are genotyped, the flock pedigree being known. In both cases, diagnostic
      tests are performed on culled animals. The less costly strategy varied according
      to the genetic context (resistant or susceptible) and to the relative costs of a
      genotyping exam and of a diagnostic test. CONCLUSION: This work demonstrates that
      combining data sources allows substantiating a flock is free from scrapie within
      a reasonable time frame. Qualification schemes could thus be a useful tool for
      voluntary or mandatory scrapie control programmes. However, there is no general
      strategy that would always minimize the costs and choice of the strategy should
      be adapted to local genetic conditions.

PMID- 19405957
TI  - Efficient context-dependent model building based on clustering posterior
      distributions for non-coding sequences.
AB  - BACKGROUND: Many recent studies that relax the assumption of independent
      evolution of sites have done so at the expense of a drastic increase in the
      number of substitution parameters. While additional parameters cannot be avoided
      to model context-dependent evolution, a large increase in model dimensionality is
      only justified when accompanied with careful model-building strategies that guard
      against overfitting. An increased dimensionality leads to increases in numerical
      computations of the models, increased convergence times in Bayesian Markov chain
      Monte Carlo algorithms and even more tedious Bayes Factor calculations. RESULTS:
      We have developed two model-search algorithms which reduce the number of Bayes
      Factor calculations by clustering posterior densities to decide on the equality
      of substitution behavior in different contexts. The selected model's fit is
      evaluated using a Bayes Factor, which we calculate via model-switch thermodynamic
      integration. To reduce computation time and to increase the precision of this
      integration, we propose to split the calculations over different computers and to
      appropriately calibrate the individual runs. Using the proposed strategies, we
      find, in a dataset of primate Ancestral Repeats, that careful modeling of context
      dependent evolution may increase model fit considerably and that the combination
      of a context-dependent model with the assumption of varying rates across sites
      offers even larger improvements in terms of model fit. Using a smaller nuclear
      SSU rRNA dataset, we show that context-dependence may only become detectable upon
      applying model-building strategies. CONCLUSION: While context-dependent
      evolutionary models can increase the model fit over traditional independent
      evolutionary models, such complex models will often contain too many parameters.
      Justification for the added parameters is thus required so that only those
      parameters that model evolutionary processes previously unaccounted for are added
      to the evolutionary model. To obtain an optimal balance between the number of
      parameters in a context-dependent model and the performance in terms of model
      fit, we have designed two parameter-reduction strategies and we have shown that
      model fit can be greatly improved by reducing the number of parameters in a
      context-dependent evolutionary model.

PMID- 19405958
TI  - The decentralisation-centralisation dilemma: recruitment and distribution of
      health workers in remote districts of Tanzania.
AB  - BACKGROUND: The implementation of decentralisation reforms in the health sector
      of Tanzania started in the 1980s. These reforms were intended to relinquish
      substantial powers and resources to districts to improve the development of the
      health sector. Little is known about the impact of decentralisation on
      recruitment and distribution of health workers at the district level. Reported
      difficulties in recruiting health workers to remote districts led the Government
      of Tanzania to partly re-instate central recruitment of health workers in 2006.
      The effects of this policy change are not yet documented. This study highlights
      the experiences and challenges associated with decentralisation and the partial
      re-centralisation in relation to the recruitment and distribution of health
      workers. METHODS: An exploratory qualitative study was conducted among informants
      recruited from five underserved, remote districts of mainland Tanzania.
      Additional informants were recruited from the central government, the NGO sector,
      international organisations and academia. A comparison of decentralised and the
      reinstated centralised systems was carried out in order to draw lessons necessary
      for improving recruitment, distribution and retention of health workers. RESULTS:
      The study has shown that recruitment of health workers under a decentralised
      arrangement has not only been characterised by complex bureaucratic procedures,
      but by severe delays and sometimes failure to get the required health workers.
      The study also revealed that recruitment of highly skilled health workers under
      decentralised arrangements may be both very difficult and expensive.
      Decentralised recruitment was perceived to be more effective in improving
      retention of the lower cadre health workers within the districts. In contrast,
      the centralised arrangement was perceived to be more effective both in recruiting
      qualified staff and balancing their distribution across districts, but poor in
      ensuring the retention of employees. CONCLUSION: A combination of centralised and
      decentralised recruitment represents a promising hybrid form of health sector
      organisation in managing human resources by bringing the benefits of two worlds
      together. In order to ensure that the potential benefits of the two approaches
      are effectively integrated, careful balancing defining the local-central
      relationships in the management of human resources needs to be worked out.

PMID- 19405959
TI  - Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and
      growth by matrix metalloproteinase-dependent and independent mechanisms.
AB  - INTRODUCTION: The stromal microenvironment has a profound influence on tumour
      cell behaviour. In tumours, the extracellular matrix (ECM) composition differs
      from normal tissue and allows novel interactions to influence tumour cell
      function. The ECM protein tenascin-C (TNC) is frequently up-regulated in breast
      cancer and we have previously identified two novel isoforms - one containing exon
      16 (TNC-16) and one containing exons 14 plus 16 (TNC-14/16). METHODS: The present
      study has analysed the functional significance of this altered TNC isoform
      profile in breast cancer. TNC-16 and TNC-14/16 splice variants were generated
      using PCR-ligation and over-expressed in breast cancer cells (MCF-7, T47D, MDA-MD
      231, MDA-MB-468, GI101) and human fibroblasts. The effects of these variants on
      tumour cell invasion and proliferation were measured and compared with the
      effects of the large (TNC-L) and fully spliced small (TNC-S) isoforms. RESULTS:
      TNC-16 and TNC-14/16 significantly enhanced tumour cell proliferation (P < 0.05)
      and invasion, both directly (P < 0.01) and as a response to transfected
      fibroblast expression (P < 0.05) with this effect being dependent on tumour cell
      interaction with TNC, because TNC-blocking antibodies abrogated these responses.
      An analysis of 19 matrix metalloproteinases (MMPs) and tissue inhibitor of matrix
      metalloproteinases 1 to 4 (TIMP 1 to 4) revealed that TNC up-regulated expression
      of MMP-13 and TIMP-3 two to four fold relative to vector, and invasion was
      reduced in the presence of MMP inhibitor GM6001. However, this effect was not
      isoform-specific but was elicited equally by all TNC isoforms. CONCLUSIONS: These
      results demonstrate a dual requirement for TNC and MMP in enhancing breast cancer
      cell invasion, and identify a significant role for the tumour-associated TNC-16
      and TNC-14/16 in promoting tumour invasion, although these isoform-specific
      effects appear to be mediated through MMP-independent mechanisms.

PMID- 19405960
TI  - Colocalization of connexin 36 and corticotropin-releasing hormone in the mouse
      brain.
AB  - BACKGROUND: Gap junction proteins, connexins, are expressed in most endocrine and
      exocrine glands in the body and are at least in some glands crucial for the
      hormonal secretion. To what extent connexins are expressed in neurons releasing
      hormones or neuropeptides from or within the central nervous system is, however,
      unknown. Previous studies provide indirect evidence for gap junction coupling
      between subsets of neuropeptide-containing neurons in the paraventricular nucleus
      (PVN) of the hypothalamus. Here we employ double labeling and retrograde tracing
      methods to investigate to what extent neuroendocrine and neuropeptide-containing
      neurons of the hypothalamus and brainstem express the neuronal gap junction
      protein connexin 36. RESULTS: Western blot analysis showed that connexin 36 is
      expressed in the PVN. In bacterial artificial chromosome transgenic mice, which
      specifically express the reporter gene Enhanced Green Fluorescent Protein (EGFP)
      under the control of the connexin 36 gene promoter, EGFP expression was detected
      in magnocellular (neuroendocrine) and in parvocellular neurons of the PVN.
      Although no EGFP/connexin36 expression was seen in neurons containing oxytocin or
      vasopressin, EGFP/connexin36 was found in subsets of PVN neurons containing
      corticotropin-releasing hormone (CRH), and in somatostatin neurons located along
      the third ventricle. Moreover, CRH neurons in brainstem areas, including the
      lateral parabrachial nucleus, also expressed EGFP/connexin 36. CONCLUSION: Our
      data indicate that connexin 36 is expressed in subsets of neuroendocrine and CRH
      neurons in specific nuclei of the hypothalamus and brainstem.

PMID- 19405962
TI  - OxDBase: a database of oxygenases involved in biodegradation.
AB  - BACKGROUND: Oxygenases belong to the oxidoreductive group of enzymes (E.C. Class
      1), which oxidize the substrates by transferring oxygen from molecular oxygen
      (O2) and utilize FAD/NADH/NADPH as the co-substrate. Oxygenases can further be
      grouped into two categories i.e. monooxygenases and dioxygenases on the basis of
      number of oxygen atoms used for oxidation. They play a key role in the metabolism
      of organic compounds by increasing their reactivity or water solubility or
      bringing about cleavage of the aromatic ring. FINDINGS: We compiled a database of
      biodegradative oxygenases (OxDBase) which provides a compilation of the oxygenase
      data as sourced from primary literature in the form of web accessible database.
      There are two separate search engines for searching into the database i.e. mono
      and dioxygenases database respectively. Each enzyme entry contains its common
      name and synonym, reaction in which enzyme is involved, family and subfamily,
      structure and gene link and literature citation. The entries are also linked to
      several external database including BRENDA, KEGG, ENZYME and UM-BBD providing
      wide background information. At present the database contains information of over
      235 oxygenases including both dioxygenases and monooxygenases. This database is
      freely available online at http://www.imtech.res.in/raghava/oxdbase/. CONCLUSION:
      OxDBase is the first database that is dedicated only to oxygenases and provides
      comprehensive information about them. Due to the importance of the oxygenases in
      chemical synthesis of drug intermediates and oxidation of xenobiotic compounds,
      OxDBase database would be very useful tool in the field of synthetic chemistry as
      well as bioremediation.

PMID- 19405961
TI  - Extracellular Hsp72, an endogenous DAMP, is released by virally infected airway
      epithelial cells and activates neutrophils via Toll-like receptor (TLR)-4.
AB  - BACKGROUND: Neutrophils play an important role in the pathophysiology of RSV,
      though RSV does not appear to directly activate neutrophils in the lower airways.
      Therefore locally produced cytokines or other molecules released by virally
      infected airway epithelial cells are likely responsible for recruiting and
      activating neutrophils. Heat shock proteins (HSPs) are generally regarded as
      intracellular proteins acting as molecular chaperones; however, HSP72 can also be
      released from cells, and the implications of this release are not fully
      understood. METHODS: Human bronchial epithelial cells (16HBE14o-) were infected
      with RSV and Hsp72 levels were measured by Western blot and ELISA. Tracheal
      aspirates were obtained from critically ill children infected with RSV and
      analyzed for Hsp72 levels by ELISA. Primary human neutrophils and differentiated
      HL-60 cells were cultured with Hsp72 and supernatants analyzed for cytokine
      production. In some cases, cells were pretreated with polymyxin B prior to
      treatment with Hsp72. IkappaBalpha was assessed by Western blot and EMSA's were
      performed to determine NF-kappaB activation. HL-60 cells were pretreated with
      neutralizing antibody against TLR4 prior to Hsp72 treatment. Neutrophils were
      harvested from the bone marrow of wild type or TLR4-deficient mice prior to
      treatment with Hsp72. RESULTS: Infection of 16HBE14o- with RSV showed an
      induction of intracellular Hsp72 levels as well as extracellular release of
      Hsp72. Primary human neutrophils from normal donors and differentiated HL-60
      cells treated with increasing concentrations of Hsp72 resulted in increased
      cytokine (IL-8 and TNFalpha) production. This effect was independent of the low
      levels of endotoxin in the Hsp72 preparation. Hsp72 mediated cytokine production
      via activation of NF-kappaB translocation and DNA binding. Using bone marrow
      derived neutrophils from wild type and TLR4-mutant mice, we showed that Hsp72
      directly activates neutrophil-derived cytokine production via the activation of
      TLR4. CONCLUSION: Collectively these data suggest that extracellular Hsp72 is
      released from virally infected airway epithelial cells resulting in the
      recruitment and activation of neutrophils.

PMID- 19405963
TI  - Role of educational level in the relationship between Body Mass Index (BMI) and
      health-related quality of life (HRQL) among rural Spanish women.
AB  - BACKGROUND: The impact of obesity on health-related quality of life (HRQL) has
      been little explored in rural areas. The goal of this study is to ascertain the
      association between obesity and HRQL among Spanish women living in a rural area,
      and the influence of their educational level. METHODS: Cross-sectional study with
      personal interview of 1298 women (aged 18 to 60) randomly selected from the
      electoral rolls of 14 towns in Galicia, a region in the north-west of Spain. HRQL
      was assessed using the SF-36 questionnaire. The association between body mass
      index (BMI) and suboptimal scores in the different HRQL dimensions was summarised
      using odds ratios (ORs), obtained from multivariate logistic regression models.
      Separate analyses were conducted for women who had finished their education
      younger than 16 years old and women with secondary education to assess
      differences in the relationship between BMI and HRQL according to educational
      level. RESULTS: Among women with primary or lower education, obesity was
      associated with a higher prevalence of suboptimal values in the following
      dimensions: Physical functioning (OR: 1.97; 95%CI: 1.22-3.18); Role-physical (OR:
      1.81; 95%CI: 1.04-3.14); General health (OR: 1.76; 95%CI: 1.10-2.81); and Role
      emotional (OR: 2.52; 95%CI: 1.27-5.03). In women with higher education, physical
      functioning was the only dimension associated with obesity (OR: 2.02: 95%CI 0.83
      4.97). CONCLUSION: The impact of obesity on women's HRQL is greater among those
      with a lower educational level. This group registered higher prevalence of
      obesity and poorer self-perceived health.

PMID- 19405964
TI  - Beneficial impacts of a national smokefree environments law on an indigenous
      population: a multifaceted evaluation.
AB  - BACKGROUND: Smokefree environments legislation is increasingly being implemented
      around the world. Evaluations largely find that the legislation is popular,
      compliance is high and report improved air quality and reduced exposure to
      secondhand smoke (SHS). The impact of the legislation on disadvantaged groups,
      including indigenous peoples has not been explored. We present findings from a
      multifaceted evaluation of the impact of the smokefree workplace provisions of
      the New Zealand Smokefree Environments Amendment Act on Maori people in New
      Zealand. Maori are the indigenous people of New Zealand. The Smokefree
      Environments Amendment Act extended existing smokefree legislation to almost all
      indoor workplaces in December 2004 (including restaurants and pubs/bars).
      METHODS: Review of existing data and commissioned studies to identify evidence
      for the evaluation of the new legislation: including attitudes and support for
      the legislation; stakeholders views about the Act and the implementation process;
      impact on SHS exposure in workplaces and other settings; and impact on smoking
      related behaviours. RESULTS: Support for the legislation was strong among Maori
      and reached 90% for smokefree restaurants and 84% for smokefree bars by 2006.
      Maori stakeholders interviewed were mostly supportive of the way the legislation
      had been introduced. Reported exposure to SHS in workplaces decreased similarly
      in Maori and non-Maori with 27% of employed adult Maori reporting SHS exposure
      indoors at work during the previous week in 2003 and 9% in 2006. Exposure to SHS
      in the home declined, and may have decreased more in Maori households containing
      one or more smokers. For example, the proportion of 14-15 year old Maori children
      reporting that smoking occurred in their home fell from 47% in 2001 to 37% in
      2007. Similar reductions in socially-cued smoking occurred among Maori and non
      Maori. Evidence for the effect on smoking prevalence was mixed. Maori responded
      to the new law with increased calls to the national Quitline service. CONCLUSION:
      The New Zealand Smokefree Environments Amendment Act had a range of positive
      effects, including reducing SHS exposure among Maori communities. If the
      experience is replicated in other countries with indigenous populations, it
      suggests that comprehensive smokefree environments legislation will have
      beneficial effects on the health of indigenous groups and could contribute to
      reducing inequalities in health within societies.

PMID- 19405965
TI  - Transcriptomic analysis of the entomopathogenic nematode Heterorhabditis
      bacteriophora TTO1.
AB  - BACKGROUND: The entomopathogenic nematode Heterorhabditis bacteriophora and its
      symbiotic bacterium, Photorhabdus luminescens, are important biological control
      agents of insect pests. This nematode-bacterium-insect association represents an
      emerging tripartite model for research on mutualistic and parasitic symbioses.
      Elucidation of mechanisms underlying these biological processes may serve as a
      foundation for improving the biological control potential of the nematode
      bacterium complex. This large-scale expressed sequence tag (EST) analysis effort
      enables gene discovery and development of microsatellite markers. These ESTs will
      also aid in the annotation of the upcoming complete genome sequence of H.
      bacteriophora. RESULTS: A total of 31,485 high quality ESTs were generated from
      cDNA libraries of the adult H. bacteriophora TTO1 strain. Cluster analysis
      revealed the presence of 3,051 contigs and 7,835 singletons, representing 10,886
      distinct EST sequences. About 72% of the distinct EST sequences had significant
      matches (E value < 1e-5) to proteins in GenBank's non-redundant (nr) and
      Wormpep190 databases. We have identified 12 ESTs corresponding to 8 genes
      potentially involved in RNA interference, 22 ESTs corresponding to 14 genes
      potentially involved in dauer-related processes, and 51 ESTs corresponding to 27
      genes potentially involved in defense and stress responses. Comparison to ESTs
      and proteins of free-living nematodes led to the identification of 554 parasitic
      nematode-specific ESTs in H. bacteriophora, among which are those encoding F-box
      like/WD-repeat protein theromacin, Bax inhibitor-1-like protein, and PAZ domain
      containing protein. Gene Ontology terms were assigned to 6,685 of the 10,886
      ESTs. A total of 168 microsatellite loci were identified with primers designable
      for 141 loci. CONCLUSION: A total of 10,886 distinct EST sequences were
      identified from adult H. bacteriophora cDNA libraries. BLAST searches revealed
      ESTs potentially involved in parasitism, RNA interference, defense responses,
      stress responses, and dauer-related processes. The putative microsatellite
      markers identified in H. bacteriophora ESTs will enable genetic mapping and
      population genetic studies. These genomic resources provide the material base
      necessary for genome annotation, microarray development, and in-depth gene
      functional analysis.

PMID- 19405967
TI  - Understanding Ferguson's delta: time to say good-bye?
AB  - A critique of Hankins, M: 'How discriminating are discriminative instruments?'
      Health and Quality of Life Outcomes 2008, 6:36.

PMID- 19405966
TI  - Geographic distribution of suitable hosts explains the evolution of specialized
      gentes in the European cuckoo Cuculus canorus.
AB  - BACKGROUND: Several types of selective forces can act to promote parasite
      specialization. Parasites might specialize on some suitable hosts at the cost of
      decreasing effectiveness when exploiting other species of hosts, and
      specialization can be more easily selected for in hosts that the parasites will
      easily find. Thus demographic characteristics of suitable hosts such as
      population density and its spatial consistency could be key factors predicting
      probability of parasite specialization and speciation. Here, we explore this
      hypothesis by studying the relationship between occurence of specialized races of
      the European cuckoo (Cuculus canorus) (i.e. gentes) and mean and coefficient of
      variation in population density estimated for 12 different European regions.
      RESULTS: The results were in accordance with the hypothesis because specialized
      cuckoo egg morphs were more common in suitable hosts with high population density
      and low variation in population density at the level of host species or genera.
      CONCLUSION: We have presented evidence suggesting that population density and
      homogeneity of geographic distribution of hosts explain, at least partly, the
      evolution of specialized egg-morphs of the European cuckoo. These results are
      consistent with the hypothesis that resource (i.e., host) predictability explains
      the evolution of host races and species of parasites.

PMID- 19405968
TI  - Using in silico models to simulate dual perturbation experiments: procedure
      development and interpretation of outcomes.
AB  - BACKGROUND: A growing number of realistic in silico models of metabolic functions
      are being formulated and can serve as 'dry lab' platforms to prototype and
      simulate experiments before they are performed. For example, dual perturbation
      experiments that vary both genetic and environmental parameters can readily be
      simulated in silico. Genetic and environmental perturbations were applied to a
      cell-scale model of the human erythrocyte and subsequently investigated. RESULTS:
      The resulting steady state fluxes and concentrations, as well as dynamic
      responses to the perturbations were analyzed, yielding two important conclusions:
      1) that transporters are informative about the internal states (fluxes and
      concentrations) of a cell and, 2) that genetic variations can disrupt the natural
      sequence of dynamic interactions between network components. The former arises
      from adjustments in energy and redox states, while the latter is a result of
      shifting time scales in aggregate pool formation of metabolites. These two
      concepts are illustrated for glucose-6 phosphate dehydrogenase (G6PD) and
      pyruvate kinase (PK) in the human red blood cell. CONCLUSION: Dual perturbation
      experiments in silico are much more informative for the characterization of
      functional states than single perturbations. Predictions from an experimentally
      validated cellular model of metabolism indicate that the measurement of cofactor
      precursor transport rates can inform the internal state of the cell when the
      external demands are altered or a causal genetic variation is introduced.
      Finally, genetic mutations that alter the clinical phenotype may also disrupt the
      'natural' time scale hierarchy of interactions in the network.

PMID- 19405969
TI  - Comparison of a high and a low intensity smoking cessation intervention in a
      dentistry setting in Sweden: a randomized trial.
AB  - BACKGROUND: Tobacco is still the number one life style risk factor for ill health
      and premature death and also one of the major contributors to oral problems and
      diseases. Dentistry may be a potential setting for several aspects of clinical
      public health interventions and there is a growing interest in several countries
      to develop tobacco cessation support in dentistry setting. The aim of the present
      study was to assess the relative effectiveness of a high intensity intervention
      compared with a low intensity intervention for smoking cessation support in a
      dental clinic setting. METHODS: 300 smokers attending dental or general health
      care were randomly assigned to two arms and referred to the local dental clinic
      for smoking cessation support. One arm received support with low intensity
      treatment (LIT), whereas the other group was assigned to high intensity treatment
      (HIT) support. The main outcome measures included self-reported point prevalence
      and continuous abstinence (> or = 183 days) at the 12-month follow-up. RESULTS:
      Follow-up questionnaires were returned from 86% of the participants. People in
      the HIT-arm were twice as likely to report continuous abstinence compared with
      the LIT-arm (18% vs. 9%, p = 0.02). There was a difference (not significant)
      between the arms in point prevalence abstinence in favour of the HIT-protocol
      (23% vs. 16%). However, point prevalence cessation rates in the LIT-arm reporting
      additional support were relatively high (23%) compared with available data
      assessing abstinence in smokers trying to quit without professional support.
      CONCLUSION: Screening for willingness to quit smoking within the health care
      system and offering smoking cessation support within dentistry may be an
      effective model for smoking cessation support in Sweden. The LIT approach is less
      expensive and time consuming and may be appropriate as a first treatment option,
      but should be integrated with other forms of available support in the community.
      The more extensive and expensive HIT-protocol should be offered to those who are
      unable to quit with the LIT approach in combination with other support. TRIAL
      REGISTRATION:  TRIAL REGISTRATION NUMBER: NCT00670514.

PMID- 19405970
TI  - Looking for a pattern: an MEG study on the abstract mismatch negativity in
      musicians and nonmusicians.
AB  - BACKGROUND: The mismatch negativity (MMN) is an early component of event-related
      potentials/fields, which can be observed in response to violations of
      regularities in sound sequences. The MMN can be elicited by simple feature (e.g.
      pitch) deviations in standard oddball paradigms as well as by violations of more
      complex sequential patterns. By means of magnetoencephalography (MEG) we
      investigated if a pattern MMN could be elicited based on global rather than local
      probabilities and if the underlying ability to integrate long sequences of tones
      is enhanced in musicians compared to nonmusicians. RESULTS: A pattern MMN was
      observed in response to violations of a predominant sequential pattern (AAAB)
      within a standard oddball tone sequence consisting of only two different tones.
      This pattern MMN was elicited even though the probability of pattern deviants in
      the sequence was as high as 0.5. Musicians showed more leftward-lateralized
      pattern MMN responses, which might be due to a stronger specialization of the
      ability to integrate information in a sequence of tones over a long time range.
      CONCLUSION: The results indicate that auditory grouping and the probability
      distribution of possible patterns within a sequence influence the expectations
      about upcoming tones, and that the MMN might also be based on global statistical
      knowledge instead of a local memory trace. The results also show that auditory
      grouping based on sequential regularities can occur at a much slower presentation
      rate than previously presumed, and that probability distributions of possible
      patterns should be taken into account even for the construction of simple oddball
      sequences.

PMID- 19405971
TI  - Survey on prevalence and risk factors on HIV-1 among pregnant women in North
      Rift, Kenya: a hospital based cross-sectional study conducted between 2005 and
      2006.
AB  - BACKGROUND: The HIV/AIDS epidemic in Kenya is a major public-health problem.
      Estimating the prevalence of HIV in pregnant women provides essential information
      for an effective implementation of HIV/AIDS control measures and monitoring of
      HIV spread within a country. The objective of this study was to determine the
      prevalence of HIV infection, risk factors for HIV/AIDS and immunologic
      (lymphocyte profile) characteristics among pregnant women attending antenatal
      clinics in three district hospitals in North-Rift, Kenya. METHODS: Blood samples
      were collected from pregnant women attending antenatal clinics in three district
      hospitals (Kitale, Kapsabet and Nandi Hills) after informed consent and pre-test
      counseling. The samples were tested for HIV antibodies as per the guidelines laid
      down by Ministry of Health, Kenya. A structured pretested questionnaire was used
      to obtain demographic data. Lymphocyte subset counts were quantified by standard
      flow cytometry. RESULTS: Of the 4638 pregnant women tested, 309 (6.7%) were HIV
      seropositive. The majority (85.1%) of the antenatal attendees did not know their
      HIV status prior to visiting the clinic for antenatal care. The highest
      proportion of HIV infected women was in the age group 21-25 years (35.5%). The 31
      35 age group had the highest (8.5%) HIV prevalence, while women aged more than 35
      years had the lowest (2.5%).Women in a polygamous relationship were significantly
      more likely to be HIV infected as compared to those in a monogamous relationship
      (p = 0.000). The highest HIV prevalence (6.3%) was recorded among antenatal
      attendees who had attended secondary schools followed by those with primary and
      tertiary level of education (6% and 5% respectively). However, there was no
      significant relationship between HIV seropositivity and the level of education (p
      = 0.653 and p = 0.469 for secondary and tertiary respectively). The mean CD4
      count was 466 cells/mm3 (9-2000 cells/mm3). Those that had less than 200
      cells/mm3 accounted for 14% and only nine were on antiretroviral therapy.
      CONCLUSION: Seroprevalence of HIV was found to be consistent with the reports
      from the national HIV sentinel surveys. Enumeration of T-lymphocyte (CD4/8)
      should be carried out routinely in the antenatal clinics for proper timing of
      initiation of antiretroviral therapy among HIV infected pregnant women.

PMID- 19405972
TI  - Evidence synthesis as the key to more coherent and efficient research.
AB  - BACKGROUND: Systematic review and meta-analysis currently underpin much of
      evidence-based medicine. Such methodologies bring order to previous research, but
      future research planning remains relatively incoherent and inefficient. METHODS:
      To outline a framework for evaluation of health interventions, aimed at
      increasing coherence and efficiency through i) making better use of information
      contained within the existing evidence-base when designing future studies; and
      ii) maximising the information available and thus potentially reducing the need
      for future studies. RESULTS: The framework presented insists that an up-to-date
      meta-analysis of existing randomised controlled trials (RCTs) should always be
      considered before future trials are conducted. Such a meta-analysis should inform
      critical design issues such as sample size determination. The contexts in which
      the use of individual patient data meta-analysis and mixed treatment comparisons
      modelling may be beneficial before further RCTs are conducted are considered.
      Consideration should also be given to how any newly planned RCTs would contribute
      to the totality of evidence through its incorporation into an updated meta
      analysis. We illustrate how new RCTs can have very low power to change inferences
      of an existing meta-analysis, particularly when between study heterogeneity is
      taken into consideration. CONCLUSION: While the collation of existing evidence as
      the basis for clinical practice is now routine, a more coherent and efficient
      approach to planning future RCTs to strengthen the evidence base needs to be
      developed. The framework presented is a proposal for how this situation can be
      improved.

PMID- 19405973
TI  - Identifying genes related to choriogenesis in insect panoistic ovaries by
      Suppression Subtractive Hybridization.
AB  - BACKGROUND: Insect ovarioles are classified into two categories: panoistic and
      meroistic, the later having apparently evolved from an ancestral panoistic type.
      Molecular data on oogenesis is practically restricted to meroistic ovaries. If we
      aim at studying the evolutionary transition from panoistic to meroistic, data on
      panoistic ovaries should be gathered. To this end, we planned the construction of
      a Suppression Subtractive Hybridization (SSH) library to identify genes involved
      in panoistic choriogenesis, using the cockroach Blattella germanica as model.
      RESULTS: We constructed a post-vitellogenic ovary library by SSH to isolate genes
      involved in choriogenesis in B. germanica. The tester library was prepared with
      an ovary pool from 6- to 7-day-old females, whereas the driver library was
      prepared with an ovary pool from 3- to 4-day-old females. From the SSH library,
      we obtained 258 high quality sequences which clustered into 34 unique sequences
      grouped in 19 contigs and 15 singlets. The sequences were compared against non
      redundant NCBI databases using BLAST. We found that 44% of the unique sequences
      had homologous sequences in known genes of other organisms, whereas 56% had no
      significant similarity to any of the databases entries. A Gene Ontology analysis
      was carried out, classifying the 34 sequences into different functional
      categories. Seven of these gene sequences, representative of different categories
      and processes, were chosen to perform expression studies during the first
      gonadotrophic cycle by real-time PCR. Results showed that they were mainly
      expressed during post-vitellogenesis, which validates the SSH technique. In two
      of them corresponding to novel genes, we demonstrated that they are specifically
      expressed in the cytoplasm of follicular cells in basal oocytes at the time of
      choriogenesis. CONCLUSION: The SSH approach has proven to be useful in
      identifying ovarian genes expressed after vitellogenesis in B. germanica. For
      most of the genes, functions related to choriogenesis are postulated. The
      relatively high percentage of novel genes obtained and the practical absence of
      chorion genes typical of meroistic ovaries suggest that mechanisms regulating
      chorion formation in panoistic ovaries are significantly different from those of
      meroistic ones.

PMID- 19405974
TI  - Endemicity response timelines for Plasmodium falciparum elimination.
AB  - BACKGROUND: The scaling up of malaria control and renewed calls for malaria
      eradication have raised interest in defining timelines for changes in malaria
      endemicity. METHODS: The epidemiological theory for the decline in the Plasmodium
      falciparum parasite rate (PfPR, the prevalence of infection) following
      intervention was critically reviewed and where necessary extended to consider
      superinfection, heterogeneous biting, and aging infections. Timelines for malaria
      control and elimination under different levels of intervention were then
      established using a wide range of candidate mathematical models. Analysis focused
      on the timelines from baseline to 1% and from 1% through the final stages of
      elimination. RESULTS: The Ross-Macdonald model, which ignores superinfection, was
      used for planning during the Global Malaria Eradication Programme (GMEP). In
      models that consider superinfection, PfPR takes two to three years longer to
      reach 1% starting from a hyperendemic baseline, consistent with one of the few
      large-scale malaria control trials conducted in an African population with
      hyperendemic malaria. The time to elimination depends fundamentally upon the
      extent to which malaria transmission is interrupted and the size of the human
      population modelled. When the PfPR drops below 1%, almost all models predict
      similar and proportional declines in PfPR in consecutive years from 1% through to
      elimination and that the waiting time to reduce PfPR from 10% to 1% and from 1%
      to 0.1% are approximately equal, but the decay rate can increase over time if
      infections senesce. CONCLUSION: The theory described herein provides simple
      "rules of thumb" and likely time horizons for the impact of interventions for
      control and elimination. Starting from a hyperendemic baseline, the GMEP planning
      timelines, which were based on the Ross-Macdonald model with completely
      interrupted transmission, were inappropriate for setting endemicity timelines and
      they represent the most optimistic scenario for places with lower endemicity.
      Basic timelines from PfPR of 1% through elimination depend on population size and
      low-level transmission. These models provide a theoretical basis that can be
      further tailored to specific control and elimination scenarios.

PMID- 19405975
TI  - Design, analysis, and presentation of crossover trials.
AB  - OBJECTIVE: Although crossover trials enjoy wide use, standards for analysis and
      reporting have not been established. We reviewed methodological aspects and
      quality of reporting in a representative sample of published crossover trials.
      METHODS: We searched MEDLINE for December 2000 and identified all randomized
      crossover trials. We abstracted data independently, in duplicate, on 14 design
      criteria, 13 analysis criteria, and 14 criteria assessing the data presentation.
      RESULTS: We identified 526 randomized controlled trials, of which 116 were
      crossover trials. Trials were drug efficacy (48%), pharmacokinetic (28%), and
      nonpharmacologic (30%). The median sample size was 15 (interquartile range 8-38).
      Most (72%) trials used 2 treatments and had 2 periods (64%). Few trials reported
      allocation concealment (17%) or sequence generation (7%). Only 20% of trials
      reported a sample size calculation and only 31% of these considered pairing of
      data in the calculation. Carry-over issues were addressed in 29% of trial's
      methods. Most trials reported and defended a washout period (70%). Almost all
      trials (93%) tested for treatment effects using paired data and also presented
      details on by-group results (95%). Only 29% presented CIs or SE so that data
      could be entered into a meta-analysis. CONCLUSION: Reports of crossover trials
      frequently omit important methodological issues in design, analysis, and
      presentation. Guidelines for the conduct and reporting of crossover trials might
      improve the conduct and reporting of studies using this important trial design.

PMID- 19405976
TI  - Evaluation of the effect of stent strut profile on shear stress distribution
      using statistical moments.
AB  - BACKGROUND: In-stent restenosis rates have been closely linked to the wall shear
      stress distribution within a stented arterial segment, which in turn is a
      function of stent design. Unfortunately, evaluation of hemodynamic performance
      can only be evaluated with long term clinical trials. In this work we introduce a
      set of metrics, based on statistical moments, that can be used to evaluate the
      hemodynamic performance of a stent in a standardized way. They are presented in
      the context of a 2D flow study, which analyzes the impact of different strut
      profiles on the wall shear stress distribution for stented coronary arteries.
      RESULTS: It was shown that the proposed metrics have the ability to evaluate
      hemodynamic performance quantitatively and compare it to a common standard. In
      the context of the simulations presented here, they show that stent's strut
      profile significantly affect the shear stress distribution along the arterial
      wall. They also demonstrates that more streamlined profiles exhibit better
      hemodynamic performance than the standard square and circular profiles. The
      proposed metrics can be used to compare results from different research groups,
      and provide an improved method of quantifying hemodynamic performance in
      comparison to traditional techniques. CONCLUSION: The strut shape found in the
      latest generations of stents are commonly dictated by manufacturing limitations.
      This research shows, however, that strut design can play a fundamental role in
      the improvement of the hemodynamic performance of stents. Present results show
      that up to 96% of the area between struts is exposed to wall shear stress levels
      above the critical value for the onset of restenosis when a tear-drop strut
      profile is used, while the analogous value for a square profile is 19.4%. The
      conclusions drawn from the non-dimensional metrics introduced in this work show
      good agreement with an ordinary analysis of the wall shear stress distribution
      based on the overall area exposed to critically low wall shear stress levels. The
      proposed metrics are able to predict, as expected, that more streamlined profiles
      perform better hemodynamically. These metrics integrate the entire morphology of
      the shear stress distribution and as a result are more robust than the
      traditional approach, which only compares the relative value of the local wall
      shear stress with a critical value of 0.5 Pa. In the future, these metrics could
      be employed to compare, in a standardized way, the hemodynamic performance of
      different stent designs.

PMID- 19405978
TI  - Daptomycin in experimental murine pneumococcal meningitis.
AB  - BACKGROUND: Daptomycin, a lipopeptide antibiotic, could be an alternative to
      vancomycin for treatment of pneumococcal meningitis. We determined the activity
      of daptomycin versus vancomycin, with dexamethasone as an adjuvant, in a murine
      model of pneumococcal meningitis. METHODS: Ninety-six 25-30 gram mice were
      inoculated intracisternally with serotype 3 Streptococcus pneumoniae modified by
      the integration of a luminescent lux operon. All mice were treated with either
      dexamethasone 1 mg/kg intraperitoneally every 6 hours alone or in combination
      with either vancomycin or daptomycin, also administered intraperitoneally. Serum
      antimicrobial concentrations were selected to approximate those achieved in
      humans. Following treatment, bioluminescence and cerebrospinal fluid (CSF)
      bacterial concentrations were determined. Caspase-3 staining was used to assess
      apoptosis on brain histopathology. RESULTS: Sixteen hours post intracisternal
      inoculation, bacterial titers in CSF were 6.8 log10 cfu/ml. Amongst the animals
      given no antibiotic, vancomycin 50 mg/kg at 16 and 20 hours or daptomycin 25
      mg/kg at 16 hours, CSF titers were 7.6, 3.4, and 3.9 log10 cfu/ml, respectively,
      at 24 hours post infection (p-value, < 0.001 for both vancomycin or daptomycin
      versus no antibiotic); there was no significant difference in bactericidal
      activity between the vancomycin and daptomycin groups (p-value, 0.18). CSF
      bioluminescence correlated with bacterial titer (Pearson regression coefficient,
      0.75). The amount of apoptosis of brain parenchymal cells was equivalent among
      treatment groups. CONCLUSION: Daptomycin or vancomycin, when given in combination
      with dexamethasone, is active in the treatment of experimental pneumococcal
      meningitis.

PMID- 19405977
TI  - Social influences upon injection initiation among street-involved youth in
      Vancouver, Canada: a qualitative study.
AB  - BACKGROUND: Street-involved youth are a population at risk of adopting injection
      as a route of administration, and preventing the transition to injection drug use
      among street youth represents a public health priority. In order to inform
      epidemiological research and prevention efforts, we conducted a qualitative study
      to investigate the initiation of injection drug use among street-involved youth
      in Vancouver, Canada. METHODS: Qualitative interviews with street youth who
      inject drugs elicited descriptions of the adoption of injection as a route of
      administration. Interviewees were recruited from the At-Risk Youth Study (ARYS),
      a cohort of street-involved youth who use illicit drugs in Vancouver, Canada.
      Audio recorded interviews were transcribed verbatim and a thematic analysis was
      conducted. RESULTS: 26 youth aged 16 to 26 participated in this study, including
      12 females. Among study participants the first injection episode frequently
      featured another drug user who facilitated the initiation of injecting. Youth
      narratives indicate that the transition into injecting is influenced by social
      interactions with drug using peers and evolving perceptions of injecting, and
      rejecting identification as an injector was important among youth who did not
      continue to inject. It appears that social conventions discouraging initiating
      young drug users into injection exist among established injectors, although this
      ethic is often ignored. CONCLUSION: The importance of social relationships with
      other drug users within the adoption of injection drug use highlights the
      potential of social interventions to prevent injection initiation. Additionally,
      developing strategies to engage current injectors who are likely to initiate
      youth into injection could also benefit prevention efforts.

PMID- 19405979
TI  - Intraoperative angiography should be standard in cerebral aneurysm surgery.
AB  - Intraoperative angiography (IOA) has proven to be a safe and effective adjunct to
      surgical repair of cerebral aneurysms. Substantial practice variation exists
      regarding use of this modality in different centers, including use of IOA
      routinely, selectively, or rarely. In this editorial, we discuss our experience
      and review the existing literature to develop an argument for routine use of IOA
      during cerebral aneurysm surgery.

PMID- 19405980
TI  - Frequency of vacA, cagA and babA2 virulence markers in Helicobacter pylori
      strains isolated from Mexican patients with chronic gastritis.
AB  - BACKGROUND: Helicobacter pylori has been strongly associated with chronic
      gastritis, peptic and duodenal ulcers, and it is a risk factor for gastric
      cancer. Three major virulence factors of H. pylori have been described: the
      vacuolating toxin (VacA), the cytotoxin-associated gene product (CagA) and the
      adhesion protein BabA2. Since considerable geographic diversity in the prevalence
      of H. pylori virulence factors has been reported, the aim of this work was to
      establish the H. pylori and vacA, cagA and babA2 gene status in 238 adult
      patients, from a marginal urban area of Mexico, with chronic gastritis. METHODS:
      H. pylori was identified in cultures of gastric biopsies by nested PCR. vacA and
      cagA genes were detected by multiplex PCR, whereas babA2 gene was identified by
      conventional PCR. RESULTS: H. pylori-positive biopsies were 143 (60.1%). All H.
      pylori strains were vacA+; 39.2% were cagA+; 13.3% were cagA+ babA2+ and 8.4%
      were babA2+. Mexican strains examined possessed the vacA s1, m1 (43.4%), s1, m2
      (24.5%), s2, m1 (20.3%) and s2, m2 (11.9%) genotypes. CONCLUSION: These results
      show that the Mexican patients suffering chronic gastritis we have studied had a
      high incidence of infection by H. pylori. Forty four percent (63/143) of the H.
      pylori strains analyzed in this work may be considered as highly virulent since
      they possessed two or three of the virulence markers analyzed: vacA s1 cagA babA2
      (9.8%, 14/143), vacA s1 babA2 (4.9%, 7/143), and vacA s1 cagA (29.4%, 42/143).
      However, a statistically significant correlation was not observed between vacAs1,
      cagA and babA2 virulence markers (chi2 test; P > 0.05).

PMID- 19405982
TI  - Lack of association between polymorphisms of MASP2 and susceptibility to SARS
      coronavirus infection.
AB  - BACKGROUND: The pathogenesis of severe acute respiratory disease syndrome (SARS)
      is not fully understood. One case-control study has reported an association
      between susceptibility to SARS and mannan-binding lectin (MBL) in China. As the
      downstream protein of MBL, variants of the MBL-associated serine protease-2
      (MASP2) gene may be associated with SARS coronavirus (SARS-CoV) infection in the
      same population. METHODS: Thirty individuals with SARS were chosen for analysis
      of MASP2 polymorphisms by means of PCR direct sequencing. Tag single nucleotide
      polymorphisms (tagSNPs) were chosen using pairwise tagging algorithms. The
      frequencies of four tag SNPs (rs12711521, rs2261695, rs2273346 and rs7548659)
      were ascertained in 376 SARS patients and 523 control subjects, using the Beckman
      SNPstream Ultra High Throughput genotyping platform. RESULTS: There is no
      significant association between alleles or genotypes of the MASP2 tagSNP and
      susceptibility to SARS-CoV in both Beijing and Guangzhou populations. Diplotype
      (rs2273346 and rs12711521)were analyzed for association with susceptibility to
      SARS, no statistically significant evidence of association was observed. The
      Beijing and Guangzhou sample groups were homogeneous regarding demographic and
      genetic parameters, a joined analysis also showed no statistically significant
      evidence of association. CONCLUSION: Our data do not suggest a role for MASP2
      polymorphisms in SARS susceptibility in northern and southern China.

PMID- 19405983
TI  - Apoptosis signal-regulating kinase 1 mediates denbinobin-induced apoptosis in
      human lung adenocarcinoma cells.
AB  - In the present study, we explore the role of apoptosis signal-regulating kinase 1
      (ASK1) in denbinobin-induced apoptosis in human lung adenocarcinoma (A549) cells.
      Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative
      mutant (ASK1DN), two antioxidants (N-acetyl-L-cysteine (NAC) and glutathione
      (GSH)), a c-Jun N-terminal kinase (JNK) inhibitor (SP600125), and an activator
      protein-1 (AP-1) inhibitor (curcumin). Treatment of A549 cells with denbinobin
      caused increases in ASK1 activity and reactive oxygen species (ROS) production,
      and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with
      denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH,
      and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1
      specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short
      interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The
      denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were
      inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results
      suggest that denbinobin might activate ASK1 through ROS production to cause
      JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results
      in A549 cell apoptosis.

PMID- 19405981
TI  - Glycogen synthase kinase-3 inhibition disrupts nuclear factor-kappaB activity in
      pancreatic cancer, but fails to sensitize to gemcitabine chemotherapy.
AB  - BACKGROUND: Aberrant activation NF-kappaB has been proposed as a mechanism of
      drug resistance in pancreatic cancer. Recently, inhibition of glycogen synthase
      kinase-3 has been shown to exert anti-tumor effects on pancreatic cancer cells by
      suppressing NF-kappaB. Consequently, we investigated whether inhibition of GSK-3
      sensitizes pancreatic cancer cells to the chemotherapeutic agent gemcitabine.
      METHODS: GSK-3 inhibition was achieved using the pharmacological agent AR-A014418
      or siRNA against GSK-3 alpha and beta isoforms. Cytotoxicity was measured using a
      Sulphorhodamine B assay and clonogenic survival following exposure of six
      different pancreatic cancer cell lines to a range of doses of either gemcitabine,
      AR-A014418 or both for 24, 48 and 72 h. We measured protein expression levels by
      immunoblotting. Basal and TNF-alpha induced activity of NF-kappaB was assessed
      using a luciferase reporter assay in the presence or absence of GSK-3 inhibition.
      RESULTS: GSK-3 inhibition reduced both basal and TNF-alpha induced NF-kappaB
      luciferase activity. Knockdown of GSK-3 beta reduced nuclear factor kappa B
      luciferase activity to a greater extent than GSK-3 alpha, and the greatest effect
      was seen with dual knockdown of both GSK-3 isoforms. GSK-3 inhibition also
      resulted in reduction of the NF-kappaB target proteins XIAP, Bcl-XL, and cyclin
      D1, associated with growth inhibition and decreased clonogenic survival. In all
      cell lines, treatment with either AR-A014418, or gemcitabine led to growth
      inhibition in a dose- and time-dependent manner. However, with the exception of
      PANC-1 where drug synergy occurred with some dose schedules, the inhibitory
      effect of combined drug treatment was additive, sub-additive, or even
      antagonistic. CONCLUSION: GSK-3 inhibition has anticancer effects against
      pancreatic cancer cells with a range of genetic backgrounds associated with
      disruption of NF-kappaB, but does not significantly sensitize these cells to the
      standard chemotherapy agent gemcitabine. This lack of synergy might be context or
      cell line dependent, but could also be explained on the basis that although NF
      kappaB is an important mediator of pancreatic cancer cell survival, it plays a
      minor role in gemcitabine resistance. Further work is needed to understand the
      mechanisms of this effect, including the potential for rational combination of
      GSK3 inhibitors with other targeted agents for the treatment of pancreatic
      cancer.

PMID- 19405984
TI  - Spirochaetes as intestinal pathogens: lessons from a Brachyspira genome.
AB  - Anaerobic spirochaetes of the genus Brachyspira have long been known as important
      gut pathogens of pigs, but increasingly they are recognised as causing disease in
      birds and other animal species, including human beings. The genome sequence of
      the major swine pathogen Brachyspira hyodysenteriae was recently published, and
      this revealed extensive genome optimisation that leads to adaptation to the
      complex environment of the colon. The genome sequences of other pathogenic and
      non-pathogenic Brachyspira species are becoming available, and this data will
      help to reveal how these species have evolved and adapted to varied lifestyles in
      the large intestines of different species, and why some but not others can induce
      colitis and diarrhoea.

PMID- 19405985
TI  - Giant right coronary artery aneurysm- case report and literature review.

PMID- 19405986
TI  - Impact of cultural differences in self on cognitive appraisals in posttraumatic
      stress disorder.
AB  - BACKGROUND: Accumulating research indicates posttraumatic stress disorder (PTSD)
      is a universal phenomenon. However, it remains substantially unknown as to
      whether the processes implicated in the aetiology and maintenance of PTSD are
      culturally similar. AIMS: This study investigated the impact of cultural
      differences in self on negative cognitive appraisals in those with and without
      PTSD. METHOD: Trauma survivors with PTSD and without PTSD from independent and
      interdependent cultures (N = 106) provided trauma narratives. Narratives were
      coded for negative cognitive appraisals (mental defeat, control strategies,
      alienation and permanent change) as in Ehlers and colleagues' previous work.
      RESULTS: Replicating Ehlers and colleagues' work, trauma survivors with PTSD from
      independent cultures reported more mental defeat, alienation, permanent change
      and less control strategies than non-PTSD trauma survivors from independent
      cultures. In contrast, for those from interdependent cultures, only alienation
      appraisals differentiated between trauma survivors with and without PTSD. Those
      with PTSD had more alienation appraisals than those without PTSD. CONCLUSIONS:
      The findings suggest cultural differences in self impact on the relationship
      between appraisals and posttraumatic psychological adjustment. Theoretical and
      clinical implications are discussed.

PMID- 19405987
TI  - Household food insecurity is a risk factor for iron-deficiency anaemia in a multi
      ethnic, low-income sample of infants and toddlers.
AB  - OBJECTIVE: The present study examines the relationships of household food
      security status with Fe deficiency (ID) and Fe-deficiency anaemia (IDA) among
      children less than 3 years of age, and associated factors that contribute to ID
      and IDA. DESIGN: Cross-sectional study and chart review. The US Food Security
      Survey Module was administered to adult caregivers as part of the Children's
      Sentinel Nutrition Assessment Project (C-SNAP). Haematological data were obtained
      from medical records. SETTING: A large metropolitan medical centre in
      Minneapolis, Minnesota, USA. SUBJECTS: A multi-ethnic sample of 2853 low-income
      children aged <36 months who received care at the medical centre. RESULTS: Among
      the caregivers, 23.3 % reported low household food security and 11.6 % reported
      very low household food security (VLFS). After controlling for background
      factors, children from households with VLFS were almost twice as likely to have
      IDA than were children from households with high or marginal food security (OR =
      1.98, 95 % CI 1.11, 3.53); the corresponding associations for ID were not
      statistically significant. CONCLUSIONS: The prevalence of IDA in early childhood
      is significantly larger in low-income infants and toddlers living in VLFS
      households. Asian, Hispanic and African-American children have elevated
      prevalences of ID and IDA. Breast-feeding may be associated with elevated ID and
      IDA, while participation in the Special Supplemental Nutrition Program for Women,
      Infants, and Children (WIC) may be protective for ID.

PMID- 19405988
TI  - Nutrition and body weights of Canadian children watching television and eating
      while watching television.
AB  - OBJECTIVE: To examine whether eating while watching television poses a risk for
      poor nutrition and excess body weight over and above that of time spent watching
      television. DESIGN: We analysed data of grade 5 students participating in a
      comprehensive population-based survey in the Canadian province of Nova Scotia.
      This survey included the Harvard's Youth Food Frequency Questionnaire, students'
      height and weight measurements, and a parent survey. We applied multivariable
      linear and logistic random effects models to quantify the associations of
      watching television and eating while watching television with diet quality and
      body weight. SETTING: The province of Nova Scotia, Canada. SUBJECTS: Grade 5
      students (n 4966). RESULTS: Eating supper while watching television negatively
      affected the consumption of fruits and vegetables and overall diet quality. More
      frequent supper while watching television was associated with more soft drink
      consumption, a higher percentage energy intake from sugar out of total energy
      from carbohydrate, a higher percentage energy intake from fat, and a higher
      percentage energy intake from snack food. These associations appeared independent
      of time children spent watching television. Both watching television and eating
      while watching television were positively and independently associated with
      overweight. CONCLUSIONS: Our observations suggest that both sedentary behaviours
      from time spent watching television as well as poor nutrition as a result of
      eating while watching television contribute to overweight in children. They
      justify current health promotion targeting time spent watching television and
      call for promotion of family meals as a means to avoid eating in front of the
      television.

PMID- 19405989
TI  - Pregnancy-related food habits among women of rural Sikkim, India.
AB  - OBJECTIVE: Every society follows its own traditional health-care beliefs and
      practices during and after pregnancy, which is intimately linked to its socio
      cultural environment. The objective of the present study was to document
      pregnancy-related food practices and the social-cultural factors linked with
      them. DESIGN: The present study was a cross-sectional one conducted among a group
      of women residing in five villages in east Sikkim, India. Mothers who had given
      birth to a child one year before the survey participated in the study. The
      mothers answered a pre-tested questionnaire on food habits and practices followed
      antepartum and for 6 weeks postpartum. SUBJECTS: The study group consisted of 199
      women of Nepali caste groups with variations in economic condition. RESULTS: More
      than 86 % of mothers consumed special foods during the postpartum period. Taboos
      on different food categories during the postpartum were reported only by 65.3 %
      of mothers. Factors found to be significantly associated with special food
      consumption were literacy status during the antepartum and parity during the
      postpartum. CONCLUSIONS: The change in consumption patterns reflects the success
      of a safe motherhood campaign propagated by the government. Detailed
      investigation in this area, involving per capita daily consumption during
      pregnancy and the postpartum period, is needed.

PMID- 19405991
TI  - Plagiarism and misconduct in scientific publishing.

PMID- 19405990
TI  - Assessing individual dietary intake from common-plate meals: a new tool for an
      enduring practice.
AB  - OBJECTIVE: The purposes of the present study were to estimate individual intake
      from common-plate meals among Bedouin Arabs using a modified 24 h recall
      questionnaire, and to evaluate reported energy intake (EI) by comparison with
      estimated energy requirement (EER). DESIGN: Weighed records were used to develop
      a method of quantifying intake from common plates. Reported EI and nutrient
      intakes were obtained from administration of the modified 24 h recall. The
      relative standard error (RSE) was used to evaluate the reliability of reported
      nutrient intakes. The FAO/WHO/United Nations University and Oxford equations and
      reported physical activity levels were used to compute ratios of reported EI to
      BMR and EER. SETTING: Population centres of traditionally semi-nomadic Bedouin
      Arabs undergoing sedentarization/urbanization in southern Israel. SUBJECTS: A
      convenience sample of 451 adults (aged 19-82 years). RESULTS: Mean (se) energy
      intake was 9648 (276) kJ/d (2306 (66) kcal/d) for men and 8230 (172) kJ/d (1967
      (41) kcal/d) for women, of which carbohydrates accounted for 63-64 %. The
      nutrient intakes evaluated had RSE ratios of less than 25 %. EI:EER ratios ranged
      from 0.86 to 0.89, and from 0.87 to 0.93 among non-dieters who ate the usual
      amount on the recall day. CONCLUSIONS: The modified 24 h recall produced
      plausible estimates of energy and nutrient intakes, comparable to those obtained
      with the 24 h recall in other populations. The modified questionnaire makes an
      important contribution to facilitating large-scale nutritional surveillance in
      the Bedouin population, and may serve as a model for modifying dietary
      instruments to quantify individual intake in other populations that practise
      common-plate eating.

PMID- 19405992
TI  - Cytochrome P450-mediated metabolism in the human gut wall.
AB  - OBJECTIVE: Although the human small intestine serves primarily as an absorptive
      organ for nutrients and water, it also has the ability to metabolise drugs.
      Interest in the small intestine as a drug-metabolising organ has been increasing
      since the realisation that it is probably the most important extrahepatic site of
      drug biotransformation. KEY FINDINGS: Among the metabolising enzymes present in
      the small intestinal mucosa, the cytochromes P450 (CYPs) are of particular
      importance, being responsible for the majority of phase I drug metabolism
      reactions. Many drug interactions involving induction or inhibition of CYP
      enzymes, in particular CYP3A, have been proposed to occur substantially at the
      level of the intestine rather than exclusively within the liver, as originally
      thought. CYP3A and CYP2C represent the major intestinal CYPs, accounting for
      approximately 80% and 18%, respectively, of total immunoquantified CYPs. CYP2J2
      is also consistently expressed in the human gut wall. In the case of CYP1A1,
      large interindividual variation in the expression levels has been reported. Data
      for the intestinal expression of the polymorphic CYP2D6 are conflicting. Several
      other CYPs, including the common hepatic isoform CYP2E1, are expressed in the
      human small intestine to only a very low extent, if at all. The distribution of
      most CYP enzymes is not uniform along the human gastrointestinal tract, being
      generally higher in the proximal regions of the small intestine. SUMMARY: This
      article reviews the current state of knowledge of CYP enzyme expression in human
      small intestine, the role of the gut wall in CYP-mediated metabolism, and how
      this metabolism limits the bioavailability of orally administered drugs. Possible
      interactions between drugs and CYP activity in the small intestine are also
      discussed.

PMID- 19405993
TI  - Evaluation of solid lipid microparticles produced by spray congealing for topical
      application of econazole nitrate.
AB  - OBJECTIVES: The aims of this study were to evaluate the suitability of the spray
      congealing technique to produce solid lipid microparticles (SLMs) for topical
      administration and to study the skin permeation of a drug from SLMs compared with
      solid lipid nanoparticles (SLNs). METHODS: Econazole nitrate was used as model
      drug and Precirol ATO 5 as the lipidic carrier. SLMs and SLNs were both prepared
      at 5:1, 10:1 and 12.5:1 lipid:drug weight ratios and characterised in terms of
      particle size, morphology, encapsulation efficiency and chemical analysis of the
      particle surface. SLMs and SLNs were also incorporated into HPMC K 100M hydrogels
      for ex-vivo drug permeation tests using porcine epidermis. KEY FINDINGS: SLMs had
      particle sizes of 18-45 microm, while SLNs showed a mean diameter of 130-270 nm.
      The encapsulation efficiency was 80-100%. Permeation profiles of econazole
      nitrate were influenced by both particle size (significant difference until 9 h)
      and the amount of lipid. CONCLUSIONS: The results confirm the usefulness of SLNs
      as carriers for topical administration and suggest the potential of SLMs for the
      delivery of drugs to the skin.

PMID- 19405994
TI  - Stress-induced cardiac insufficiency relating to abnormal leptin and FKBP12.6 is
      ameliorated by CPU0213, an endothelin receptor antagonist, which is not affected
      by the CYP3A suppressing effect of erythromycin.
AB  - OBJECTIVES: Cardiac injury induced by isoprenaline produces stress. This stress
      can be mediated by the activated endothelin and leptin pathway; thus, the
      endothelin receptor antagonist CPU0213 may reverse these changes. CPU0213 is
      metabolized mainly by cytochrome P450 (CYP)3A, thus, erythromycin, an inhibitor
      of CYP3A, could affect its effects by raising its plasma levels. METHODS: Forty
      rats were divided into five groups. Group 1 rats were normal. Group 2 rats were
      administered isoprenaline (1 mg/kg, s.c.) for 10 days. Groups 3, 4 and 5 were
      administered isoprenaline, but group 3 was given erythromycin (100 mg/kg, p.o.)
      alone on days six to ten, group 4 was given CPU0213 20 mg/kg (s.c.) on days six
      to ten, whilst group 5 received erythromycin plus CPU0213 on days six to ten.
      Measurements were conducted to observe changes in the haemodynamics, cardiac
      weight index, serum lactate dehydrogenase and creatine kinase levels, and
      expression of endothelin receptor A (ETA), leptin and its OBRb receptor. KEY
      FINDINGS: In isoprenaline-treated rats, cardiac hypertrophy and dysfunction were
      found. This was associated with upregulated myocardial leptin protein and OBRb
      receptor mRNA. Immunohistochemical assay of ETA was upregulated, accompanied with
      downregulation of FKBP12.6 (calstabin 2) in isoprenaline-treated rats. These
      effects were significantly reversed by CPU0213. HPLC assay presented an increased
      plasma level of CPU0213 by erythromycin, but no change in its effects.
      CONCLUSIONS: CPU0213 improved isoprenaline-induced cardiomyopathy by modulating
      ETA, leptin and FKBP12.6. However, erythromycin increased plasma levels but did
      not change its effects.

PMID- 19405996
TI  - RT-PCR analysis of ABC, SLC and SLCO drug transporters in human lung epithelial
      cell models.
AB  - OBJECTIVES: Carrier-mediated transport mechanisms play crucial roles in drug
      absorption and elimination processes, as well as in the transport of endogenous
      molecules affecting cellular regulation and function. In this study we used RT
      PCR analysis to characterise the mRNA transcript expression of a wide range of
      membrane carrier transporters in several in-vitro lung epithelial cell models.
      Transporters studied included: 11 ATP-binding cassette (ABC) transporters, 11
      solute carrier (SLC) transporters and 9 solute carrier organic anion (SLCO)
      transporters. METHODS: The cell culture models included both established cell
      lines (A549, Calu-3, 16HBE14o-, BEAS-2B) and freshly isolated lung epithelial
      cells in primary culture (human bronchial and alveolar epithelial cells). KEY
      FINDINGS: The expression profiles of several clinically relevant drug
      transporters were characterised using RT-PCR analysis. Our results showed
      differential transporter expression in cell culture models from different regions
      of the lung and also highlighted disparities when comparing lung cell lines with
      primary cell culture models. Differences in transporter expression between cell
      models of pulmonary and gastrointestinal origin were also noted. CONCLUSIONS: The
      information will guide and validate the use of in-vitro lung epithelial cell
      lines in the study of pulmonary administered drugs and candidate molecules.

PMID- 19405995
TI  - Amitriptyline inhibits the activity of the rat glutamate transporter EAAT3
      expressed in Xenopus oocytes.
AB  - OBJECTIVES: Evidence suggests that glutamatergic systems may be involved in the
      pathophysiology of major depression and the mechanism of action of
      antidepressants. We have investigated the effects of amitriptyline, a tricyclic
      antidepressant, on the activity of the excitatory amino acid transporter type 3
      (EAAT3), a protein that can regulate extracellular glutamate concentrations in
      the brain. METHODS: EAAT3 was expressed in Xenopus oocytes. Using a two-electrode
      voltage clamp, membrane currents were recorded after application of 30 microM L
      glutamate in the presence or absence of various concentrations of amitriptyline
      or after application of various concentrations of L-glutamate in the presence or
      absence of 0.64 microM amitriptyline. KEY FINDINGS: Amitriptyline concentration
      dependently reduced EAAT3 activity. This inhibition reached statistical
      significance at 0.38-1.27 microM amitriptyline. Amitriptyline 0.64 microM reduced
      the pharmacokinetic parameter Vmax, but did not affect the pharmacokinetic
      parameter Km, of EAAT3 for L-glutamate. The amitriptyline inhibition disappeared
      after a 4-min washout. Phorbol-12-myristate-13-acetate, a protein kinase C
      activator, increased EAAT3 activity. However, 0.64 microM amitriptyline induced a
      similar degree of decrease in EAAT3 activity in the presence or absence of
      phorbol-12-myristate-13-acetate. CONCLUSIONS: Our results suggested that
      amitriptyline at clinically relevant concentrations reversibly reduced EAAT3
      activity via decreasing its maximal velocity of glutamate transporting function.
      The effects of amitriptyline on EAAT3 activity may have represented a novel site
      of action for amitriptyline to increase glutamatergic neurotransmission. Protein
      kinase C may not have been involved in the effects of amitriptyline on EAAT3.

PMID- 19405997
TI  - Effects of quinidine on antinociception and pharmacokinetics of morphine in rats.
AB  - AIM: The aim of this study was to investigate the effect of quinidine, a P
      glycoprotein inhibitor, on the pharmacokinetics and pharmacodynamics of morphine
      in rats. METHODS: Rats were given morphine (30 mg/kg p.o. or 30 mg/kg over 10 min
      i.v.) 30 min after pretreatment with quinidine (30 mg/kg p.o.). Antinociceptive
      effects were determined using the tail immersion test. Concentrations of morphine
      in plasma and brain were also determined. KEY FINDINGS: The antinociception of
      morphine was significantly enhanced by oral administration of quinidine, with a
      3.1-fold greater area under the effect-time curve than that in vehicle-treated
      rats. Morphine concentrations in plasma and brain were significantly increased by
      quinidine. The area under the plasma concentration-time curve after oral or
      intravenous administration of morphine was increased 5.2- and 1.7-fold,
      respectively, in quinidine-pretreated rats compared with vehicle-pretreated rats.
      Quinidine caused a 40% decrease in the total clearance of morphine and increased
      the concentration of morphine in the brain, although the brain-to-plasma
      concentration ratio was not changed. CONCLUSIONS: Oral administration of
      quinidine increases the absorption of morphine from the gastrointestinal tract
      and subsequently enhances the concentration in the brain and its antinociceptive
      effect. Enhanced intestinal absorption of morphine may be due largely to
      inhibition of intestinal P-glycoprotein by quinidine.

PMID- 19405998
TI  - Specific aminopeptidases of excised human nasal epithelium and primary culture: a
      comparison of functional characteristics and gene transcripts expression.
AB  - OBJECTIVES: To investigate whether growing human nasal epithelium as primary
      cultures alters aminopeptidase B (APB), aminopeptidase N (APN) and
      dipeptidyldipeptidase (DPPIV) metabolic characteristics, and mRNA gene transcript
      expression. METHODS: The formation of 7-amino-methyl coumarin from specific
      substrates for APN (L-alanine-4-methyl-coumaryl-7-amide, APB (L-arginine-4-methyl
      coumaryl-7-amide) and DPPIV (glycyl-L-proline-4-methyl-coumaryl-7-amide) was used
      to estimate the KM, Vmax and the effect of aminopeptidases inhibitors on the
      enzymes. Polymerase chain reaction was used to investigate gene expression. KEY
      FINDINGS: Results of this study showed that: (1) both the excised tissues and
      primary cultures of human nasal epithelium expressed APN, APB and DPPIV activity;
      (2) the KM of APB, APN and DPPIV was not significantly different in cell and
      tissue homogenates; (3) except for APN, the Vmax was not significantly different
      in the two metabolism models; (4) there was no statistically significant
      difference in the behaviours of APB, APN and DPPIV in response to inhibition by
      puromycin and bestatin in the two models; (5) the mRNA transcripts that encode
      APB, APN and DPPIV were expressed in both cell culture and tissue homogenate.
      CONCLUSIONS: Based on the results of this study, it may be concluded that nasal
      primary culture system is suitable for investigating peptide and protein
      metabolism and enzymatic stability in human nasal epithelium. Except for APN, the
      tissue culture conditions did not significantly alter the functional and
      molecular expression of the aminopeptidases.

PMID- 19405999
TI  - The importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism
      for the separation of analgesic and antipyretic effects of lornoxicam in rats
      with paw inflammation.
AB  - OBJECTIVES: Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits
      strong analgesic and anti-inflammatory effects but a weak antipyretic effect in
      rat models. Our aim was to investigate the mechanism of separation of potencies
      or analgesic and antipyretic effects of lornoxicam in relation to its effect on
      prostaglandin E2 (PGE2) production in the inflammatory paw and the brain.
      METHODS: A model of acute or chronic paw inflammation was induced by Freund's
      complete adjuvant injection into the rat paw. Lornoxicam (0.01-1 mg/kg),
      celecoxib (0.3-30 mg/kg) or loxoprofen (0.3-30 mg/kg) was administered orally to
      the rats and the analgesic and antipyretic effects were compared. The paw
      hyperalgesia was assessed using the Randall-Selitto test or the flexion test.
      Dorsal subcutaneous body temperature was measured as indicator of pyresis. After
      the measurement of activities, the rats were sacrificed and the PGE2 content in
      the paw exudate, cerebrospinal fluid or brain hypothalamus was measured by enzyme
      immunoassay. KEY FINDINGS: In a chronic model of arthritis, lornoxicam, celecoxib
      and loxoprofen reduced hyperalgesia with an effective dose that provides 50%
      inhibition (ED50) of 0.083, 3.9 and 4.3 mg/kg respectively, whereas the effective
      dose of these drugs in pyresis was 0.58, 0.31 and 0.71 mg/kg respectively. These
      drugs significantly reduced the PGE2 level in paw exudate and the cerebrospinal
      fluid. In acute oedematous rats, lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and
      loxoprofen 2.4 mg/kg significantly reduced hyperalgesia to a similar extent. On
      the other hand, lornoxicam did not affect the elevated body temperature, whereas
      celecoxib and loxoprofen significantly reduced the pyrexia to almost the normal
      level. These drugs significantly reduced the PGE2 level in inflamed paw exudate
      lo almost the normal level. On the other hand, lornoxicam did not change PGE2
      level in the brain hypothalamus, whereas celecoxib and loxoprofen strongly
      decreased it. CONCLUSIONS: Lornoxicam exhibits strong analgesic but weak
      antipyretic effects in rats with paw inflammation. Such a separation of effects
      is related to its efficacy in the reduction of PGE2 levels in the paw and brain
      hypothalamus.

PMID- 19406000
TI  - Influence of dosing schedules on toxicity and antitumour effects of combined
      cisplatin and docetaxel treatment in mice.
AB  - OBJECTIVES: The combination of cisplatin and docetaxel shows a better cure rate
      against non-small-cell lung cancer than other drug combinations in clinical
      studies; however, severe myelosuppression and nephrotoxicity are dose-limiting
      factors. The purpose of this study was to establish a suitable dosing schedule to
      reduce adverse effects and improve the antitumour effects. METHODS: Cisplatin and
      docetaxel were administered i.p. to male ICR mice simultaneously, or sequentially
      with either cisplatin or docetaxel first followed by the second drug 12 h later
      (docetaxel-cisplatin and cisplatin-docetaxel groups). Antitumour effects of these
      schedules were also tested in C57BL/6N mice bearing Lewis lung carcinomas. KEY
      FINDINGS: The simultaneous docetaxel/cisplatin group showed the lowest survival
      rate and the highest blood urea nitrogen (BUN) concentration. Cisplatin
      concentrations in the plasma and kidney were higher in the simultaneous dosing
      group than the sequential dosing groups. Antitumour effect was the greatest in
      the docetaxel-cisplatin group. CONCLUSIONS: The docetaxel-cisplatin regimen
      inhibited tumour growth the best and reduced mortality and nephrotoxicity.

PMID- 19406001
TI  - Mechanisms involved in the antinociceptive and anti-inflammatory effects of bis
      selenide in mice.
AB  - OBJECTIVES: The present study examined the mechanisms involved in the
      antinociceptive effects of bis selenide [(Z)-2,3-bis(4-chlorophenylselanyl)prop-2
      en-1-ol]. METHODS: The effects of oral bis selenide were tested against licking
      behaviour and oedema in mice induced by formalin, serotonin, histamine,
      glutamate, phorbol 12-myristate 13-acetate (PMA), 8-bromoadenosine 3',5'-cyclic
      monophosphate (8-BrcAMP) and prostaglandin E2. The effects of a variety of
      receptor antagonists on the antinociceptive activity were tested to determine the
      likely mechanism of action of bis selenide. KEY FINDINGS: Bis selenide caused
      antinociception on the first and second phases of the formalin test, with mean
      ID50 values of 34.21 (29.66-39.45) and 15.86 (12.17-20.67) mg/kg and maximal
      inhibition of 65+/-3% and 90+/-1%, respectively. At 50 mg/kg bis selenide
      significantly inhibited (31+/-2%) paw oedema induced by intraplantar injection of
      formalin. At 25 mg/kg given 5 min after the formalin injection, bis selenide
      caused a significant inhibition (42+/-5%) in the second phase of the formalin
      test, whereas the prophylactic treatment caused more intense inhibition (64+/
      3%). Oral administration of bis selenide reduced licking and paw oedema induced
      by serotonin, histamine, glutamate, PGE2, PMA and 8-BrcAMP. The antinociceptive
      effect of bis selenide (25 mg/kg, p.o.) on the formalin test was reversed by i.p.
      administration of p-chlorophenylalanine methyl ester (an inhibitor of serotonin
      synthesis), ketanserin (a selective 5-HT2A receptor antagonist), ondansetron (a 5
      HT3 receptor antagonist) and ranitidine (a histamine H2-receptor antagonist).
      CONCLUSIONS: Glutamatergic, prostaglandin E2, serotonergic (5-HT2A and 5-HT3) and
      histamine H2 receptors are involved in the antinociceptive effects of bis
      selenide in mice. The interaction of bis selenide with protein kinase C and A
      signalling pathways was also demonstrated.

PMID- 19406002
TI  - Pharmacological and metabolic characterisation of the potent sigma1 receptor
      ligand 1'-benzyl-3-methoxy-3H-spiro[[2]benzofuran-1,4'-piperidine].
AB  - OBJECTIVES: The pharmacology and metabolism of the potent sigma1 receptor ligand
      1'-benzyl-3-methoxy-3H-spiro[[2]benzofuran-1,4'-piperidine] were evaluated.
      METHODS: The compound was tested against a wide range of receptors, ion channels
      and neurotransmitter transporters in radioligand binding assays. Analgesic
      activity was evaluated using the capsaicin pain model. Metabolism by rat and
      human liver microsomes was investigated, and the metabolites were identified by a
      variety of analytical techniques. KEY FINDINGS: 1'-benzyl-3-methoxy-3H
      spiro[[2]benzofuran-1,4'-piperidine] (compound 1) is a potent sigma1 receptor
      ligand (Ki 1.14 nM) with extraordinarily high sigma1/sigma2 selectivity (>1100).
      It was selective for the sigma1 receptor over more than 60 other receptors, ion
      channels and neurotransmitter transporters, and did not interact with the human
      ether-a-go-go-related gene (hERG) cardiac potassium channel. Compound 1 displayed
      analgesic activity against neuropathic pain in the capsaicin pain model (53%
      analgesia at 16 mg/kg), indicating that it is a sigma1 receptor antagonist. It
      was rapidly metabolised by rat liver microsomes. Seven metabolites were
      unequivocally identified; an N-debenzylated metabolite and a hydroxylated
      metabolite were the major products. Pooled human liver microsomes formed the same
      metabolites. Studies with seven recombinant cytochrome P450 isoenzymes revealed
      that CYP3A4 produced all the metabolites identified. The isoenzyme CYP2D6 was
      inhibited by 1 (IC50 88 nM) but did not produce any metabolites. CONCLUSIONS: 1'
      benzyl-3-methoxy-3H-spiro[[2]benzofuran-1,4'-piperidine] is a potent and
      selective sigma1 receptor antagonist, which is rapidly metabolised. Metabolically
      more stable sigma1 ligands could be achieved by stabilising the N-benzyl
      substructure.

PMID- 19406004
TI  - Identification of in-vivo and in-vitro metabolites of palmatine by liquid
      chromatography-tandem mass spectrometry.
AB  - OBJECTIVES: Despite its important therapeutic value, the metabolism of palmatine
      is not yet clear. Our objective was to investigate its in-vivo and in-vitro
      metabolism. METHODS: Liquid chromatography-tandem electrospray ionization mass
      spectrometry (LC-ESI/MSn) was employed in this work. In-vivo samples, including
      faeces, urine and plasma of rats, were collected after oral administration of
      palmatine (20 mg/kg) to rats. In-vitro samples were prepared by incubating
      palmatine with intestinal flora and liver microsome of rats, respectively. All
      the samples were purified via a C18 solid-phase extraction procedure, then
      chromatographically separated by a reverse-phase C18 column with methanol-formic
      acid aqueous solution (pH 3.5, 70:30 v/v) as mobile phase, and detected by an on
      line MSn detector. The structure of each metabolite was elucidated by comparing
      its molecular weight, retention time and full-scan MSn spectra with those of the
      parent drug. KEY FINDINGS: The results revealed that 12 metabolites were present
      in rat faeces, 13 metabolites in rat urine, 7 metabolites in rat plasma, 10
      metabolites in rat intestinal flora and 9 metabolites in rat liver microsomes.
      Except for six of the metabolites in rat urine, the other in-vivo and in-vitro
      metabolites were reported for the first time. CONCLUSIONS: Seven new metabolites
      of palmatine (tri-hydroxyl palmatine, di-demethoxyl palmatine, tri-demethyl
      palmatine, mono-demethoxyl dehydrogen palmatine, di-demethoxyl dehydrogen
      palmatine, mono-demethyl dehydrogen palmatine, tri-demethyl dehydrogen palmatine)
      were reported in this work.

PMID- 19406003
TI  - Endothelium-independent vasorelaxation by the selective alpha estrogen receptor
      agonist propyl pyrazole triol in rat aortic smooth muscle.
AB  - OBJECTIVES: This study investigated the signalling mechanism of the relaxant
      responses to the estrogen receptor (ERalpha) agonist PPT (propyl pyrazole triol)
      in endothelium-denuded rat aortic rings. METHODS: Several compounds, including
      protein kinase G (PKG) inhibitors and potassium channel inhibitors, were tested
      against PPT-dependent rat aortic relaxation. Cyclic GMP and cytosolic calcium
      responses to PPT in isolated aortic smooth muscle were investigated in parallel.
      KEY FINDINGS: PPT vasorelaxation was largely reduced by the selective ERalpha
      antagonist methyl-piperidinopyrazole (MPP; -91.6+/-2.5%), by the selective PKG
      inhibitor Rp-8-Br-cGMP (-78.6+/-4.9%), by the specific soluble guanylyl cyclase
      inhibitor ODQ (1H-(1,2,4)-oxadiazolo[4,3-a]quinoxalin-1-one; -85.3+/-5.2%) and to
      a lesser extent by the selective BKCa (large-conductance calcium- and voltage
      activated potassium channel) inhibitor iberiotoxin (-59.3%), the selective IKCa
      (intermediate-conductance calcium-activated potassium channel) inhibitor TRAM-34
      (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole; -50.7%) and the voltage-gated
      potassium channel inhibitor 4-aminopyridine (-40.8%). In isolated aortic smooth
      muscle, PPT strongly enhanced the cyclic GMP content (+144%) and Rp-8-Br-cGMP
      largely reduced the PPT-dependent calcium signal (-80.8%). CONCLUSIONS: ERalpha
      receptor stimulation in rat aortic smooth muscle evokes a PKG-signalling pathway,
      likely triggering relaxation by BKCa and IKCa channel opening.

PMID- 19406005
TI  - Novel action of 7-O-galloyl-D-sedoheptulose isolated from Corni Fructus as a
      hypertriglyceridaemic agent.
AB  - OBJECTIVES: We investigated the lipid-lowering activity of 7-O-galloyl-D
      sedoheptulose, an active component of Corni Fructus, and related mechanisms.
      METHODS: Rats were fed a high-fructose diet for 6 days, followed by treatment
      with 7-O-galloyl-D-sedoheptulose, 5, 10 or 20 mg/kg per day, or fenofibrate
      (positive control). KEY FINDINGS: The high-fructose diet induced an increase in
      body weight, hypertriglyceridaemia, hyperglycaemia and hypertension.
      Administration of 7-O-galloyl-D-sedoheptulose significantly reduced the levels of
      triglyceride in the serum and liver (being more effective than fenofibrate) but
      did not lead to changes in liver weight or hepatic function, whereas fenofibrate
      increased the liver weight markedly. The preventive effect of 7-O-galloyl-D
      sedoheptulose against the accumulation of triglyceride and cholesterol was
      related to the up-regulation of peroxisome proliferator-activated receptor alpha
      expression. CONCLUSIONS: The present study supports the role of 7-O-galloyl-D
      sedoheptulose as a promising agent against hypertriglyceridaemia without hepatic
      side-effects.

PMID- 19406006
TI  - Silymarin inhibits melanin synthesis in melanocyte cells.
AB  - OBJECTIVES: The aim was to search for inhibitors of melanogenesis from natural
      resources. METHODS: The inhibitory effect of silymarin on melanogenesis in a
      spontaneously immortalized mouse melanocyte cell line, Mel-Ab, was studied. KEY
      FINDINGS: Silymarin significantly prevented melanin production in a dose
      dependent manner with an IC50 value (concentration producing 50% maximal
      inhibition) of 28.2 microg/ml, without effects on cell viability. Also, silymarin
      inhibited L-DOPA oxidation activity of tyrosinase, the rate-limiting melanogenic
      enzyme, in cell based-systems but it did not directly affect cell-free tyrosinase
      activity. Furthermore, Western blot analysis indicated that silymarin decreased
      the expression of tyrosinase protein. CONCLUSIONS: This study suggests that the
      depigmenting effect of silymarin might be attributable to inhibition of
      tyrosinase expression and that silymarin may be useful as a natural skin
      lightening agent.

PMID- 19406007
TI  - Brain targeting studies on buspirone hydrochloride after intranasal
      administration of mucoadhesive formulation in rats.
AB  - OBJECTIVES: The purpose of this study was to find out whether nasal application
      of buspirone could increase its bioavailability and directly transport the drug
      from nose to brain. METHODS: A nasal formulation (Bus-chitosan) was prepared by
      dissolving 15.5 mg buspirone hydrochloride, 1% w/v chitosan hydrochloride and 5%
      w/v hydroxypropyl beta-cyclodextrin (HP-beta-CD) in 5 ml of 0.5% sodium chloride
      solution. The formulation was nasally administered to rats and the plasma and
      brain concentration compared with that for buspirone hydrochloride solution after
      intravenous and intranasal (Bus-plain) administration. The brain drug uptake was
      also confirmed by gamma scintigraphic study. KEY FINDINGS: The nasal Bus-chitosan
      formulation improved the absolute bioavailability to 61% and the plasma
      concentration peaked at 30 min whereas the peak for nasal Bus-plain formulation
      was 60 min. The AUC0-480 in brain after nasal administration of Bus-chitosan
      formulation was 2.5 times that obtained by intravenous administration (711+/-252
      ng/g vs 282+/-110 ng/g); this was also considerably higher than that obtained
      with the intranasal Bus-plain formulation (354+/-80 ng/g). The high percentage of
      direct drug transport to the brain (75.77%) and high drug targeting index (>1)
      confirmed the direct nose to brain transport of buspirone following nasal
      administration of Bus-chitosan formulation. CONCLUSIONS: These results
      conclusively demonstrate increased access of buspirone to the blood and brain
      from intranasal solution formulated with chitosan and HP-beta-CD.

PMID- 19406008
TI  - Effect of sodium houttuyfonate on myocardial hypertrophy in mice and rats.
AB  - OBJECTIVES: The aim of the study was to determine the effect of sodium
      houttuyfonate on myocardial hypertrophy and its mechanism of action in mice and
      rats. METHODS: A mouse model of myocardial hypertrophy was established by
      subcutaneous injection with isoproterenol. Mice were randomly divided into five
      groups: normal control; isoproterenol control; isoproterenol plus metoprolol;
      isoproterenol plus low- and high-dose sodium houttuyfonate. A rat model of
      myocardial hypertrophy was established by intraperitoneal injection with L
      thyroxine. Rats were randomly divided into five groups: normal control; L
      thyroxine control; L-thyroxine plus captopril; L-thyroxine plus low- and high
      dose sodium houttuyfonate. At the end of the experiments, the left ventricular
      weight index and heart weight index were determined in mice and rats, the size of
      cardiomyocytes was measured in rats and the concentrations of cAMP in plasma and
      angiotensin II in ventricular tissue of mice were detected by radioimmunoassay.
      The endothelin-1 concentration was measured by radioimmunoassay and the
      hydroxyproline content was measured by a digestive method in ventricular tissue
      of rats. KEY FINDINGS: After 7-9 days of treatment, sodium houttuyfonate
      significantly reduced the left ventricular weight index and heart weight index in
      mice and rats with myocardial hypertrophy, decreased the size of cardiomyocytes
      in rats, and reduced the content of cAMP and angiotensin II in mice with
      myocardial hypertrophy. It also decreased the endothelin-1 concentration and the
      hydroxyproline content in ventricular tissue in rats. CONCLUSIONS: Sodium
      houttuyfonate can inhibit myocardial hypertrophy in mouse and rat models by
      restricting the activity of the sympathetic nervous system and decreasing the
      levels of angiotensin II and endothelin-1 in ventricular tissue.

PMID- 19406010
TI  - Response surface optimization for determination of volatile organic compounds in
      water samples by headspace-gas chromatography-mass spectrometry method.
AB  - The determination of benzene, toluene, p-xylene, tetrachloroethene,
      chlorobenzene, and dibromomethane in water by headspace analysis combined with
      gas chromatography-mass spectrometry (HS-GC-MS) has been investigated. An
      optimization strategy for the analysis of the six volatile organic compounds
      (VOCs) is presented with the experimental design and response surface methodology
      aid. Thermostatting time, temperature, and salt quantity were optimized by using
      a central composite design, and quadratic models relating peak areas to the three
      factors were built. The mathematical models were tested on a number of simulated
      data set and had a coefficient of R2>0.98. The factor effects were visualized as
      three-dimensional response surfaces and contour plots. The optimal conditions
      were achieved in 36.8 min, at 90 degrees C, and with 6 g of NaCl. The method
      showed a good agreement between the experimental data and predictive values
      throughout the studied parameter space, and was suitable for optimization studies
      of the VOCs in water by the HS-GC-MS method.

PMID- 19406009
TI  - Retraction.

PMID- 19406011
TI  - Photodegradation of crude oil on a solid support.
AB  - The modifications of crude oil after absorption on silica, montmorillonite, and
      zeolite were studied. Solid-phase microextraction gas chromatography-mass
      spectrometry analysis showed that some compounds are kept better by the solid
      support than other ones. The modifications that occurred were studied considering
      the relative amount of different classes of compounds, the number of compounds in
      function of the number of carbon atoms, and the relative amount in function of
      the number of carbon atoms for different classes of compounds (linear alkanes,
      branched alkanes, cyclic alkanes, aromatic hydrocarbons, and alkenes). The
      modifications which occurred after irradiation with a 125 W high pressure mercury
      arc towards Pyrex were studied. A global index of the modifications which
      occurred was proposed. All of the solids prevent photodegradation. Zeolite was
      the worst, while the most preservative effect was showed by montmorillonite.

PMID- 19406012
TI  - GC determination of acetone, acetaldehyde, ethanol, and methanol in biological
      matrices and cell culture.
AB  - A gas chromatography with flame ionization detection method (GC-FID) with direct
      injection, using a capillary column, was validated to determine ethanol,
      acetaldehyde, methanol, and acetone in different human matrices, such as whole
      blood, vitreous humour, and urine, with clinical and forensic interest. This
      method was also employed to quantify these compounds in cell culture medium, thus
      being useful in basic research. A good peak resolution was achieved, with linear
      correlation between concentration and peak areas for all the compounds in all the
      matrices. The inter- and intra-day precisions of the method were always under 15%
      and 10%, respectively. The accuracy of the method, calculated as the percentage
      of the target concentration, was within the acceptable limits. The obtained
      limits of detection were below 0.85 mg/L for acetaldehyde and below 0.75 mg/L for
      the other considered compounds. The small injection volume and the high split
      ratios applied, allied to the high performance of the GC column, resulted in very
      good peak resolution and high sensitivities. This method is easy to perform,
      making it suitable for the routine of clinical biochemistry and forensic
      laboratories.

PMID- 19406013
TI  - GC and mass spectral studies on acylated side chain regioisomers of 3-methoxy-4
      methyl-phenethylamine and 4-methoxy-3-methyl-phenethylamine.
AB  - The side chain regioiomers of the 3-methoxy-4-methylphenethylamines and 4-methoxy
      3-methyl-phenethylamines have mass spectra essentially equivalent to the
      controlled drug substance 3,4-methylenedioxymethamphetamine (3,4-MDMA), all have
      molecular weight of 193 and major fragment ions in their electron ionization mass
      spectra at m/z 58 and 135/136. Furthermore, the compounds in this study have ring
      substitutions in the same relative positions as 3,4-MDMA. The nonequivalence of
      the substituents (methoxy and methyl) yields two sets of compounds, 3-methoxy-4
      methyl- and 4-methoxy-3-methylphenethylamines. The perfluoroacyl derivatives
      (pentafluoropropionylamides and heptafluorobutrylamides) of the primary and
      secondary regioisomeric amines were prepared and evaluated in gas chromatography
      mass spectrometry studies. The mass spectra for these derivatives are
      significantly individualized and the resulting unique fragment ions allow for
      specific side chain identification. The heptafluorobutrylamide derivatives offer
      more fragment ions than the pentafluoropropionylamides for molecular
      individualization among these regioisomeric substances. These acylated
      derivatives show excellent resolution on a dimethyl polysiloxane stationary phase
      such as Rtx-1.

PMID- 19406014
TI  - Determination of camphor and borneol in Flos Chrysanthemi Indici by UAE and GC
      FID.
AB  - In the work, ultrasonic-assisted extraction (UAE) followed by gas chromatography
      with flame ionization detector (GC-FID) is developed for the quantitative
      analysis of the bioactive components of camphor and borneol in a traditional
      Chinese medicine (TCM) of Flos Chrysanthemi Indici. The extraction parameters are
      investigated. The optimum extraction conditions found are: solvent, methanol;
      solvent to sample ratio, 12:1 (v/w); extraction time, 15 min. Camphor and borneol
      are determined using this extraction method in Flos Chrysanthemi Indici samples
      from 5 different growing areas. The relative standard deviation values for
      camphor and borneol are 8.4% and 5.6%, respectively. The recoveries for camphor
      and borneol are 89% and 95%, respectively, and the method detection limits are
      lower than 0.23 microg/mL. To demonstrate the method feasibility, steam
      distillation is also used to analyze camphor and borneol in Flos Chrysanthemi
      Indici samples from these different growing areas. The statistical comparison by
      t-test (95% confidence level) showed no significant difference between these
      results. It has been shown that the proposed UAE-GC-FID is a simple, rapid, and
      reliable method for quantitative analysis of camphor and borneol in TCM, and a
      potential tool for quality assessment of Flos Chrysanthemi Indici.

PMID- 19406016
TI  - Mixed sorbent phases for thick film open tubular traps.
AB  - In this work, we present a technique for the preparation of tailor-made sorbent
      phases for thick film open tubular traps. Solid or liquid polymers are dispersed
      in a polydimethylsiloxane (PDMS) pre-polymer, which is cross-linked in situ after
      coating. The technique is evaluated by preparing thick film open tubular traps
      with PDMS containing solid or liquid poly(ethylene glycol) (PEG). A significant
      increase in retention for polar analytes is observed, even when only 7.5% PEG is
      present. The increase in retention for 3-chloro-1,2-propanediol is more than
      tenfold. The preparation method is simple and no solvents are required. Also, the
      concept provides great flexibility in terms of phase composition.

PMID- 19406015
TI  - Study of the alarming volatile characteristics of Tessaratoma papillosa using
      SPME-GC-MS.
AB  - The stinkbug's volatile compositions would alter very much before and after
      stinkbugs were disturbed or irritated, which caused the alarming effect. An
      efficient headspace solid-phase microextraction sampling method was established
      to study the alarming volatile characteristics and potential alarming volatiles
      of stinkbugs (Tessaratoma papillosa) followed by gas chromatography-mass
      spectrometry detection. The number of volatiles identified was 16 and 22 before
      and after stinkbug irritation, respectively. Long-chain alkanes, alkenes, and
      alcohols consisted of the main volatile compositions of Tessaratoma papillosa.
      When stinkbugs were disturbed, the typical unsaturated volatiles were released,
      especially including a series of tridecane derivatives. In comparison with the
      volatile compounds of lichi leaf and flower (plants the stinkbug eats), it could
      be seen that most stinkbug alarming volatiles were synthesized by the insects
      themselves, and that they do not originate from their food. The different
      statistical alarming volatile characteristics of Tessaratoma papillosa before and
      after irritation were interpreted by principal component analysis in the original
      Chromatography Data Processing System. However, temperature and light did not
      affect the alarming volatile characteristics. The variety of the stinkbug
      alarming volatile characteristics before and after irritation was specified by
      common model strategy. Tridecane, [E]-2-hexenal, dodecane, [E]-2-hexen-1-ol
      acetate, and 2,3-dimethyl-1-pentene contributed most to the various alarming
      volatile characteristics before and after irritation, which might be the
      potential alarming volatiles. It is hoped that this work will provide useful
      information for insect control.

PMID- 19406017
TI  - An isocratic HPLC method for the simultaneous determination of cholesterol,
      cardiolipin, and DOPC in lyophilized lipids and liposomal formulations.
AB  - Phospholipids, such as 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and
      1,1',2,2'-tetramyristoyl cardiolipin, along with cholesterol, form liposomes in
      aqueous media and have been investigated at NeoPharm (Lake Bluff, IL) as drug
      delivery systems. To accurately assess the effectiveness of various formulations
      involving the use of aforementioned phospholipids and cholesterol, their
      quantitative determination is essential. An isocratic high-performance liquid
      chromatographic method for the simultaneous determination of cholesterol,
      cardiolipin, and DOPC in various pharmaceutical formulations containing the
      active drug substance has consequently been developed and is presented here. The
      current method utilizes an ASTEC-diol analytical column and is shown to be
      stability-indicating and free from interference from any of the formulation
      excipients, such as sucrose, sodium chloride, and sodium lactate. The analytes
      are detected using an evaporative light scattering detector (Alltech or Polymer
      Laboratories). The quantitation of each lipid component is performed using non
      linear regression analysis. The retention characteristics of the analytes are
      examined as a function of eluent composition (e.g., pH, salt content, organic to
      aqueous phase ratio) and column temperature. The method was validated and was
      found to be sensitive, specific, rugged, and cost-effective. The current method
      provides enhanced chromatographic separation for lipid components as well as
      degradation products as compared to similar methods reported in the literature.
      It is also inherently simpler than other similar methods reported in the
      literature that typically use complex gradient elution.

PMID- 19406018
TI  - Validation of single isocratic HPLC method for the assay of valdecoxib and
      determination of metaisomer impurity.
AB  - A sensitive and accurate isocratic high-performance liquid chromagraphic method
      is developed for the determination of both metaisomer impurity and assay of
      valdecoxib drug substance. This method uses a Phenomenex Luna C18 (2) column, a
      mobile phase of 60:30:10 (v/v) 20 mM NaH2PO4, methanol, and tetrahydrofuran,
      respectively, with UV detection. This method is validated and its stability
      indicating capability is established by performing stress studies under acidic,
      basic, oxidation, light, humidity, and thermal conditions. Valdecoxib is well
      separated from its metaisomer impurity with a resolution of more than 2.0. The
      limit of detection of 0.007% is obtained for the metaisomer impurity, and the
      relative response factor is also determined. Repeatability is good, with a
      relative standard deviation of not more than 0.2% and 0.8% for the assay and
      impurity methods, respectively. A system suitability test is developed with
      acceptance criteria and the requirements are met throughout the method
      validation. The method is validated as robust to variations in chromatographic
      conditions.

PMID- 19406019
TI  - Low level determination of 4-amino-2-ethoxy-cinnamic acid and its ethyl ester in
      a drug substance and its formulation prototypes by HPLC-UV-DAD.
AB  - A reversed-phase high-performance liquid chromatographic method (HPLC) with diode
      array detection (DAD) has been evaluated for monitoring trace levels of
      impurities, such as 4-amino-2-ethoxy-cinnamic acid (impurity A), hydrochloride
      salt of 4-amino-2-ethoxy-ethyl cinnamate (impurity B), and 4-bromo-3-ethoxy
      nitrobenzene (impurity C), in drug substance and 3 different formulation
      prototypes. These compounds have been highlighted as potential genotoxins and 2
      ethoxy-4-amino-cinnamic acid (impurity A) as possible degradant isolated during
      the synthesis of BI drug substance. HPLC-UV-DAD was found to be more promising,
      and limits of quantification were between 0.09 and 0.6 microg/mL, which enabled
      detection limits in drug substance at 2-15 ppm for a 15 mg/mL solution. All three
      genotoxic impurities are completely resolved from each other as well as from
      diluent peaks, drug substance, and other related impurities within 40 min. The
      retention times of impurities A, B, and C were 3.4, 13.1, and 21.3 min. The
      results demonstrating the specificity, assay precision, recovery, linearity, and
      range achieved during the method validation experiments are presented in this
      paper.

PMID- 19406020
TI  - Effect of trace amounts of water in the mobile phase of normal-phase
      enantioselective high-performance liquid chromatography on selectivity and
      resolution of optical isomers.
AB  - The irreproducibility of normal-phase enantioselective high-performance liquid
      chromatography (HPLC) could be attributed to the presence or absence of trace
      amounts of water in one or more components of the mobile phase. The effect of
      trace amounts of water on chromatographic characteristics in normal-phase
      enantioselective HPLC was investigated by deliberate addition of controlled,
      trace amounts of water into the mobile phase for the separation of T-3811ME and
      its undesired enantiomer. Commercial 2-propanol was pre-mixed with 2% (v/v) water
      and then used for preparation of the mobile phase in combination with such
      organic modifiers as ethanol and methanol at different ratios. The results showed
      up to 30% improvement in the resolution (Rs), 4% in selectivity (alpha), and 39%
      in efficiency (plate number N) compared to using a mobile phase prepared from
      neat commercial 2-propanol. Thus, the effect of trace amounts of water in the
      mobile phase of normal-phase enantioselective HPLC was demonstrated.

PMID- 19406023
TI  - Updates in infertility treatment.

PMID- 19406021
TI  - Simultaneous determination of salbutamol, ractopamine, and clenbuterol in animal
      feeds by SPE and LC-MS.
AB  - A liquid chromatography-mass spectrometry (LC-MS) method for the simultaneous
      determination of salbutamol, ractopamine, and clenbuterol in commercial feeds was
      developed. Samples were extracted with phosphoric acid-methanol solution, and
      further clean-up was achieved with a C18 cation exchange mixed mode cartridge.
      Separation of analytes was developed on a C18 column with 0.01 M aqueous ammonium
      formate solution (pH 3.8)-acetonitrile by gradient program, and characterized by
      LC-MS on a quadrupole detector, in electrospray positive ion mode. This method
      provides average recoveries for salbutamol, ractopamine, and clenbuterol of 83
      110% and coefficients of variation of 1.5-11% in feeds spiked in the range of 0.5
      500 mg/kg. The limits of detection and quantification in feeds were 0.01 mg/kg
      and 0.05 mg/kg, respectively. Such limits are well below the dose of 2-25 mg/kg
      feed proposed as effective.

PMID- 19406024
TI  - HIV and reproductive health: a South African experience.
AB  - Acquired immune deficiency syndrome (AIDS), caused by the human immunodeficiency
      virus (HIV), disproportionately affects Africa whereby the majority of new
      infections and deaths occur in sub-Saharan Africa. It is the leading cause of
      death in Africa and a major cause of maternal mortality. HIV/AIDS impacts on
      every aspect of reproductive health and presents considerable challenges to
      healthcare systems. Fertility is particularly valued in Africa and voluntary
      childlessness is unusual. AIDS results in a reduction in both fecundity and
      fertility, as well as compromising the outcome of pregnancy. The stigma of
      childlessness is quite profound and impacts both social life and social standing
      within the community, particularly of the women who are affected. Unfortunately,
      treatment for infertility is often inadequate and, because of limited resources,
      is frequently denied to HIV-positive couples. Undoubtedly the challenges in
      dealing with the HIV/AIDS pandemic in Africa are enormous; however, appropriate
      solutions are available and these need to be put in place. It is essential that
      the management of the HIV patient is holistic and takes all needs, including that
      of fertility, into account.

PMID- 19406025
TI  - Demographics of infertility.
AB  - The demographic composition of many developed countries threatens their economies
      and global influence. On the one hand, the increased cost of living and of
      raising children discourages couples from starting families until later in life
      while, on the other hand, improved living standards have increased life
      expectancy. Together, these have resulted in a low total fertility rate and a net
      increase in the elderly population. The financial and employment protection
      incentives offered by governments have had relatively little impact on this
      demographic trend, and a multi-level approach is needed. Governments are,
      therefore, considering alternatives as part of a so-called 'population policy
      mix'. One option is to promote access to assisted reproductive technology for
      infertile couples. The prevalence of infertility has increased, in part because
      of general health issues, such as obesity and the rise in sexually transmitted
      diseases, and also because women are postponing having their first child.
      Improving accessibility to assisted reproductive technology will relieve the
      burden of infertility on these couples and may contribute to effectively
      challenging the problem of low total fertility rates in many developed countries.

PMID- 19406026
TI  - International evolution of legislation and guidelines in medically assisted
      reproduction.
AB  - The most noticeable characteristic of the legal situation in Europe regarding
      medically assisted reproduction is the enormous variety of rules. It is hard to
      find two countries with the same rules regarding a topic like embryo research or
      donor insemination. Moreover, there has been a rapid evolution of the law and
      regulation of medically assisted reproduction in the last 15 years. This legal
      mosaicism is threatened by increasing pressure from politicians and international
      societies. Three topics are discussed in this article: (i) the relationship
      between ethics and politics, and the impact on national legislation; (ii) the
      evaluation of international legal harmonization; and (iii) alternative solutions
      to some of the problems. It is concluded that consensus and harmonization only
      has moral value when it is brought about by discussion and persuasion, not by
      force.

PMID- 19406027
TI  - Human corpus luteum physiology and the luteal-phase dysfunction associated with
      ovarian stimulation.
AB  - The human corpus luteum is a temporary endocrine gland that develops after
      ovulation from the ruptured follicle during the luteal phase. It is an important
      contributor of steroid hormones, particularly progesterone, and is critical for
      the maintenance of early pregnancy. Luteal-phase dysfunction can result in
      premature regression of the gland, with a subsequent shift to an infertile cycle.
      Understanding the mechanism of steroidogenesis during corpus luteum growth and
      regression is crucial for evaluating the normal physiology and pathophysiology of
      reproductive cycles. The rate-limiting step in corpus luteum steroidogenesis is
      the transport of cholesterol to the site of steroid production. Steroidogenic
      acute regulatory protein is a key player in this process and is positively
      correlated with progesterone concentrations throughout the early and mid-luteal
      phase. Changes in the endocrine environment brought on by the gonadotrophins used
      for ovarian stimulation are thought to underlie the corpus luteum dysfunction
      associated with IVF cycles. While ovarian hyperstimulation syndrome is associated
      with human chorionic gonadotrophin (HCG), studies suggest that exogenous
      progesterone provides necessary luteal support in patients undergoing IVF. The
      current trend towards simple stimulation protocols and the use of single-embryo
      transfers provide further opportunity to revisit HCG administration as luteal
      support.

PMID- 19406028
TI  - Identifying real differences in live birth rates between HMG and rFSH in IVF.
AB  - Fertility treatment strives for the delivery of a healthy live birth. Human
      menopausal gonadotrophin (HMG) and recombinant FSH (rFSH) are the two types of
      gonadotrophin currently used for ovarian stimulation in assisted reproduction
      treatments. Although both HMG and rFSH have been shown to be effective, a number
      of studies have examined whether a potential difference in clinical benefit or
      outcome exists between treatments. Unlike rFSH preparations, HMG contains both
      FSH and LH activity (in the form of LH and human chorionic gonadotrophin, which
      are short- and long-acting, respectively). The beneficial effect of exogenous LH
      activity has been investigated in the Menotrophin versus Recombinant FSH in-vitro
      Fertilisation Trial (MERiT), which revealed differences in embryo quality and
      endometrial receptivity between rFSH and highly purified HMG. Current evidence
      suggests that HMG provides significantly higher live birth rates than rFSH in
      women undergoing ovarian stimulation for in-vitro fertilization/intracytoplasmic
      sperm injection cycles using long gonadotrophin-releasing hormone agonist
      protocol. Further studies will continue to provide data with which to expand
      these findings and optimize the chances of achieving a live birth following
      assisted reproduction treatment.

PMID- 19406029
TI  - Benefits of luteinizing hormone activity in ovarian stimulation for IVF.
AB  - Knowledge of the physiology of folliculogenesis has led to a better understanding
      of the role of LH activity in this process. This role has been investigated in
      the setting of ovarian stimulation and several treatment modalities have been
      proposed. LH activity can be provided in the forms of: (i) human menopausal
      gonadotrophins (HMG), (ii) recombinant LH (rLH), (iii) human chorionic
      gonadotrophin (HCG), and (iv) recombinant HCG (rHCG). Current evidence suggests
      that ovarian stimulation performed with HMG in patients treated with a long
      gonadotrophin releasing hormone (GnRH) agonist protocol seems to result in
      increased (3-4%) clinical pregnancy rates compared with recombinant FSH (rFSH).
      Data regarding the short GnRH agonist or GnRH antagonist protocol are scarce and
      firm conclusions cannot be drawn. Administration of rLH prior or during ovarian
      stimulation with rFSH does not seem to increase the probability of pregnancy.
      Existing data suggest that HCG is capable of partially or completely replacing
      FSH administration during the mid-to-late follicular phase of an ovarian
      stimulation cycle, leading to a decreased requirement for FSH, without
      compromising pregnancy rates. High quality evidence originating from randomized
      controlled trials regarding the potential value of rHCG administration during
      ovarian stimulation for IVF is not available.

PMID- 19406030
TI  - Role of the endocrine profile for the achievement of pregnancy with IVF.
AB  - The predictive value of pre-ovulatory hormones for achievement of pregnancy has
      been extensively evaluated in assisted reproductive technologies. Currently, no
      high-quality evidence exists to support or deny an association between oestradiol
      levels on the day of human chorionic gonadotrophin (HCG) administration and
      pregnancy achievement in IVF cycles. Retrospective studies appear to support the
      lack of such an association. Progesterone elevation on the day of HCG
      administration does not appear to be associated with the probability of clinical
      pregnancy in women undergoing IVF. Finally, no retrospective studies exist to
      suggest that low endogenous midfollicular LH concentrations are associated with a
      significantly decreased probability of ongoing pregnancy beyond 12 weeks of
      gestation in IVF. In two prospective studies, high endogenous LH concentrations
      during down-regulation were associated with a decreased probability of ongoing
      pregnancy beyond 12 weeks of gestation. Existing studies evaluating the
      association between single measurements of pre-ovulatory hormones and the
      achievement of pregnancy are of low quality and cannot lead to solid conclusions.
      Based on the available literature, it appears that no association exists between
      single assessments of oestradiol, progesterone or LH, and pregnancy achievement.

PMID- 19406031
TI  - Ovarian stimulation and embryo quality.
AB  - To study the effects of different ovarian stimulation approaches on oocyte and
      embryo quality, it is imperative to assess embryo quality with a reliable and
      objective method. Embryos rated as high quality by standardized morphological
      assessment are associated with higher implantation and pregnancy rates. However,
      embryo morphology on day 3 after fertilization is not a reliable indication of a
      normal chromosomal constitution. Therefore, using embryo morphology as the sole
      parameter for embryo quality is not ideal. Screening of embryos for chromosomal
      aneuploidies before transfer can be used to assess the chromosomal competence of
      embryos, which has been shown to have a direct relationship with the approach
      used for ovarian stimulation. However, gene expression analysis of cumulus
      granulosa cells is a promising non-invasive technique for determining embryo
      quality. Cumulus cells are closely associated with oocytes, and oocyte-cumulus
      cell communication is vital to oocyte development. Cumulus cells respond to both
      gonadotrophins and paracrine factors from oocytes, with a distinct gene
      expression pattern. Future approaches analysing the expression of relevant genes
      in cumulus cells using real-time polymerase chain reaction may enable us to
      monitor the consequences of different stimulation protocols and identify the
      underlying molecular mechanisms by which they influence oocyte/embryo quality.

PMID- 19406033
TI  - Uterine dynamics: impact on the human reproduction process.
AB  - This review assesses data on the possible relationship between the contractility
      of the non-pregnant uterus and the human reproduction process. The possibility of
      assessing non-invasively uterine contractility using ultrasound scans has
      improved understanding of hormone regulation and the influence of uterine
      contractility on the human embryo implantation process in both natural and
      ovarian stimulation cycles. Contractions of the non-pregnant uterus are
      influenced by ovarian hormones and, presumably, partake in the in-vivo
      fertilization and embryo implantation processes in humans. Approaches aimed at
      either stimulating or inhibiting uterine contractions could be instrumental in
      improving pregnancy rates after the use of assisted reproductive technologies.

PMID- 19406032
TI  - Maintenance of genetic integrity during natural and assisted reproduction.
AB  - The essence of reproduction involves propagation of genetic information from
      parents to offspring. In mammals, the frequency of spontaneously acquired
      mutations is lower in germ-line cells than in somatic cells, reflecting the role
      played by germline cells in the propagation of genetic information and the
      importance of maintaining genetic integrity in these cells. The Big Blue((R))
      transgenic mouse model was used to investigate the frequency and spectrum of: (i)
      spontaneous point mutations in germ cells as they develop naturally during the
      life cycle of the mouse; and (ii) acquired mutations that are normally
      transmitted from parents to offspring during natural and assisted reproduction.
      The study found that germ cells normally maintain a frequency of spontaneous
      point mutations that is 5-10-fold lower than that observed in somatic cells from
      the same individual, leading to embryos with very low frequencies of point
      mutations in the next generation. No significant differences in the frequency or
      spectrum of mutations between naturally conceived fetuses and assisted-conception
      fetuses were observed, indicating that, with respect to maintenance of genetic
      integrity, these methods are safe. Preliminary analysis of fetuses produced by
      somatic cell nuclear transfer indicates that maintenance of genetic integrity is
      regulated in a tissue-specific manner by epigenetic mechanisms that are subject
      to reprogramming during cloning.

PMID- 19406034
TI  - Single-embryo transfer versus multiple-embryo transfer.
AB  - Despite the progress made in assisted reproductive technology, live birth rates
      remain disappointingly low. Multiple-embryo transfer has been an accepted
      practice with which to increase the success rate. This has led to a higher
      incidence of multiple-order births compared with natural conception, which not
      only increase the risk of mortality and morbidity to both mother and children but
      are also associated with social and economic consequences. Elective single-embryo
      transfer (eSET) was developed in an effort to increase singleton pregnancies in
      assisted reproduction. Studies comparing eSET with multiple-embryo transfer
      highlight the benefit of this approach and suggest that, with careful patient
      selection and the transfer of good-quality embryos, the risk of a multiple-order
      pregnancy can be reduced without significantly decreasing live birth rates.
      Although the use of eSET has gradually increased in clinical practice, its
      acceptance has been limited by factors such as availability of funding and
      awareness of the procedure. An open discussion of eSET is warranted in an effort
      to enable a broader understanding by physicians and patients of the merits of
      this approach. Ultimately, eSET may provide a more cost-effective, potentially
      safer approach to patients undergoing assisted reproduction technology.

PMID- 19406035
TI  - How to avoid ovarian hyperstimulation syndrome: a new indication for dopamine
      agonists.
AB  - Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic
      complication associated with ovarian stimulation. Despite the numerous
      breakthroughs that have been made in other areas of assisted reproduction
      technology, it is only in recent years that the understanding of OHSS has
      advanced sufficiently to develop treatment options aimed at reducing the
      incidence and effects of OHSS. However, suitable predictors and tests with which
      to identify susceptible patients remain unreliable, although anti-Mullerian
      hormone is currently a good risk-factor candidate. More progress has been made
      with the prevention of OHSS, and physicians now have a wide range of treatment
      options, including coasting, re-initiation of gonadotrophin-releasing hormone
      (GnRH) antagonist and induction of a luteinizing hormone flare-up using GnRH
      agonist. Recently, vascular endothelial growth factor (VEGF) has been identified
      as a key player in the vascular permeability that is associated with OHSS. The
      use of the dopamine agonist cabergoline has been found to reduce the effects of
      VEGF-mediated vascular permeability without compromising implantation and
      pregnancy rates. Together, these treatments will complement the ongoing progress
      with other procedures such as in-vitro maturation and oocyte vitrification, and
      enable physicians to improve the prediction and prevention of OHSS.

PMID- 19406036
TI  - Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells:
      necessity of immunosuppressive treatment for sustained improvement.
AB  - OBJECTIVE: The purpose of the present study was to examine the efficacy of
      transplantation of mouse embryonic stem (ES) into Parkinson's disease (PD) model
      mice as well as the necessity of immunosuppression in allogeneic donor-host
      combinations. MATERIALS AND METHODS: ES cells, derived from SvJ129 strain mice,
      were differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro by
      an embryoid body (EB)-based multistep differentiation method and used as graft
      cells for PD mice, which were prepared by injection of 6-hydroxydopamine (OHDA)
      into C57BL/6, BALB/c and C3H/HeN strains. Mice from each strain were divided into
      Groups 1-3. Four weeks after the 6-OHDA injection, Group 1 received phosphate
      buffered saline in the striatum wounds, while Group 2 received 2 x 10(4) graft
      cells, and Group 3 mice received 2 x 10(4) graft cells and were also treated with
      cyclosporine A. RESULTS: Apomorphine-induced rotational behavior was improved in
      Groups 2 and 3, but not in Group 1. However, the behavioral improvement ceased
      later in Group 2, whereas sustained improvement was observed in Group 3
      throughout the 8 week observation period after transplantation. ES-derived TH(+)
      cells were found at the grafted sites at the end of the experiment in Groups 2
      and 3, and tended to be more abundant in Group 3. CONCLUSION: Intra-striatum
      transplantation of ES-derived dopaminergic neurons was effective in treating PD
      mice, even in allogeneic donor-host combinations. Immunosuppressive treatment did
      not have an effect on initial behavioral restoration after transplantation;
      however, it was necessary for sustained improvement over a prolonged period.

PMID- 19406037
TI  - Nicotine tolerance to PC12 cell line: acute and chronic exposures modulate
      dopamine D2 receptor and tyrosine hydroxylase expression.
AB  - PC12 is a clonal cell line from chromaffin tumor of rat adrenal pheochromocytoma
      that releases catecholamine including dopamine, which via interaction with its
      receptor (D(1) and D(2) receptor), is known to be involved in reward and
      reinforcement properties of many addictive drugs like nicotine. Nicotine
      tolerance is the key aspect of nicotine addiction. However, nicotine tolerance on
      dopamine receptors in PC12 cell line is poorly understood. In this paper, we have
      demonstrated the tolerance to acute and chronic nicotine administrations on PC12
      cell line on the basis of the expressions of dopamine receptors and tyrosine
      hydroxylase, the rate-limiting enzyme of dopamine biosynthesis, by Western blot,
      immunohistochemistry and in situ hybridization. In vitro treatment of nicotine
      resulted in similar expressional changes of dopamine D(2) receptor and tyrosine
      hydroxylase at protein and mRNA levels in dose- and time-dependent manner,
      whereas dopamine D(1) receptor did not reveal any positive output. Moreover,
      moderate to strong signals were obtained from 0.1 to 10 microM of nicotine
      concentrations and the signals were gradually decreased at 100 and 1000 microM
      nicotine concentrations relative to the untreated control cell line. Therefore,
      this study implied a new approach towards nicotine tolerance which is likely to
      be related to the modulation of dopamine D(2) receptor and tyrosine hydroxylase
      expressions by chronic and acute nicotine exposures in PC12 cell line.

PMID- 19406038
TI  - SPIKES for difficult conversations with cancer patients.

PMID- 19406040
TI  - Selection of patients with hepatocellular carcinoma for sorafenib.
AB  - Sorafenib, a multitargeted anti-VEGF receptor and raf kinase inhibitor, was
      recently approved by the FDA for treating unresectable hepatocellular carcinoma
      (HCC) based on 2 randomized phase III studies. In addition, a phase II study
      evaluating sorafenib in patients with HCC and Child-Pugh A and B and a phase I
      study evaluating sorafenib in patients with organ dysfunction have provided
      insight about the safety and efficacy of sorafenib in patients with HCC and more
      advanced cirrhosis, and any difference in outcome based on etiology of HCC. The
      lack of objective responses observed in the sorafenib arm in the SHARP study also
      raises practical issues about how to assess response or efficacy of the therapy
      and thus how long a patient should receive sorafenib. This article addresses
      these questions on the use of sorafenib in HCC, both in the locally advanced and
      metastatic settings, in addition to the potential future applications and uses of
      sorafenib.

PMID- 19406041
TI  - Transplantation for hepatocellular carcinoma and cholangiocarcinoma.
AB  - Hepatocellular carcinoma (HCC) and cholangiocarcinoma represent more than 95% of
      primary hepatic malignancies in adults. The incidence of both seems to be rising.
      Any form of cirrhosis and primary sclerosing cholangitis represent independent
      risk factors for the development of HCC and cholangiocarcinoma, respectively. The
      surgical treatment of these malignancies has evolved significantly in the past
      decade, and liver transplantation (LT) has revolutionized the prognosis of these
      conditions. Provided both malignancies are diagnosed early in their natural
      history, LT offers a greater than 75% chance of survival at 4 years. This is a
      remarkable improvement in the treatment of primary hepatic malignancies and
      compares favorably with any other form of treatment, including partial liver
      resection. The application of specific pretransplantation staging criteria, along
      with the addition of neoadjuvant chemoradiation therapy for cholangiocarcinoma,
      has made these results possible. The development of living donor LT further
      expands the treatment horizon for both diseases. It also lessens the impact of
      the scarcity of available deceased donor organs available for transplantation.
      The future challenge is to better characterize biologic staging/prognostic
      indicators that could expand the understanding and success in treating both
      malignancies.

PMID- 19406042
TI  - Increasing incidence of intrahepatic cholangiocarcinoma and its relationship to
      chronic viral hepatitis.
AB  - Primary liver cancer is the sixth most common cancer and third most common cause
      of cancer death worldwide. Cholangiocarcinoma is the second most common primary
      liver tumor after hepatocellular carcinoma. Because the incidence of intrahepatic
      cholangiocarcinoma is rising in most areas worldwide, identification of the main
      causes of this problem is urgently needed. Despite well-known risk factors in the
      development of intrahepatic cholangiocarcinoma, recent reports focus on chronic
      hepatitis B and C viral infections because an increasing number of studies have
      observed an association. The relationship, however, is still not conclusive
      because of the diversity in clinical reports and the lack of in vitro evidences.
      This issue should be emphasized and further investigation is required for
      clarification.

PMID- 19406044
TI  - A communication approach for oncologists: understanding patient coping and
      communicating about bad news, palliative care, and hospice.
AB  - Oncologists frequently approach patients to discuss difficult topics, such as bad
      news about cancer progression and referrals to palliative care and hospice. To
      communicate effectively in these difficult situations, it is helpful to assess
      what the patient knows and wants to know about their disease in general and,
      specifically, their prognosis. Although some patients fully accept the diagnosis
      of cancer and cope well, most patients struggle with how best to cope. This
      struggle often manifests itself with the patient vacillating between unrealistic
      hopes for longevity while also indicating prognostic awareness by talking about
      funeral plans. Although this coping is normal, it is difficult for most
      clinicians to interpret. This article presents a framework for understanding
      normal patient coping and gives specific examples of how to talk with these
      patients during difficult transitions, such as times of disease progression, and
      about referral to hospice and palliative care.

PMID- 19406043
TI  - NCCN clinical practice guidelines in oncology: palliative care.

PMID- 19406045
TI  - Palliative care across the continuum of cancer care.
AB  - Optimal oncology care requires the integration of palliative medicine into
      oncology care across the disease trajectory. All patients require screening for
      palliative care services at the initial oncologic visit and reassessment
      throughout the continuum of care. As a result of the increasing attention focused
      on palliative care nationally and internationally, the domains of palliative
      cancer care have been elucidated and have fostered the development of guidelines
      for quality palliative care. The recent recognition of palliative medicine as a
      subspecialty in the United States, the growing number of hospital-based
      palliative care programs, and the accreditation of palliative medicine fellowship
      programs by the Accreditation Council for Graduate Medical Education highlight
      the increased visibility of palliative medicine. This provides hope for the
      future of oncologic care. The palliative approach is subsumed in cancer care--it
      provides assistance with decision-making, symptom management, and access to
      financial, emotional, and spiritual services. A fully integrated program of
      oncology and palliative care provides the greatest opportunity for care and cure.

PMID- 19406039
TI  - NCCN clinical practice guidelines in oncology: hepatobiliary cancers.

PMID- 19406046
TI  - Diagnostic strategies using DNA testing for hereditary haemochromatosis in at
      risk populations: a systematic review and economic evaluation.
AB  - OBJECTIVE: To evaluate DNA testing for detecting hereditary haemochromatosis
      (HHC) in subgroups of patients suspected of having the disorder and in family
      members of those diagnosed with HHC. DATA SOURCES: Major electronic databases,
      searched from inception to April 2007. REVIEW METHODS: A systematic review was
      undertaken using a priori methods and a de novo model developed to assess costs
      and consequences of DNA testing. RESULTS: Eleven studies were identified for
      estimating the clinical validity of genotyping for the C282Y mutation for the
      diagnosis of HHC. No clinical effectiveness studies meeting the inclusion
      criteria were identified. Two North American cost-effectiveness studies of
      reasonable quality were identified but their generalisability to the UK is not
      clear. Three cohort studies met the inclusion criteria for the review of
      psychosocial aspects. All had methodological limitations and their
      generalisability is difficult to determine. The clinical sensitivity of C282Y
      homozygosity for HHC ranged from 28.4% to 100%, or from 91.3% to 92.4% when
      considering only the most relevant studies. Clinical specificity ranged from
      98.8% to 100%. One study found that gene testing was a cost-effective method of
      screening relatives of patients with haemochromatosis, whereas the other found
      that genotyping the spouse of a homozygote was the most cost-efficient strategy.
      Genetic testing for haemochromatosis appears to be well accepted, is accompanied
      by few negative psychosocial outcomes and may lead to reduced anxiety. The de
      novo economic model showed that, in people suspected of having haemochromatosis,
      the DNA strategy is cost saving compared with the baseline strategy using liver
      biopsy (cost saved per case detected 123 pounds), largely because of the
      reduction in liver biopsies. For family testing of siblings the DNA strategy is
      not cost saving because of the costs of the DNA test (additional cost per case
      detected 200 pounds). If the cost of the test were to reduce from 100 pounds to
      60 pounds, the DNA strategy would be the cheaper one. For family testing of
      offspring the DNA test strategy is cheaper than the baseline biochemical testing
      strategy (cost saved per case detected 7982 pounds). Sensitivity analyses showed
      that the conclusions in each case are robust across all reasonable parameter
      values. CONCLUSIONS: The preferred strategy in practice is DNA testing in
      conjunction with testing iron parameters when there is clear clinical indication
      of risk for haemochromatosis because of biochemical criteria or when there is
      familial risk for HHC. Access to genetic testing and centralisation of test
      provision in expert laboratories would lower the cost of testing, improve the
      cost-effectiveness of the strategy and improve the quality of information
      provided to clinicians and patients.

PMID- 19406048
TI  - [18F-fluorodeoxyglucose positron emission tomography in the evaluation of therapy
      response assessment in lymphomas. Systematic literature review and meta
      analysis].
AB  - This systematic review of literature analyze the utility of positron emission
      tomography (PET or PET-CT) with 18F-fluorodeoxyglucose, as a diagnostic tool in
      the assessment of response to chemotherapy and immunotherapy in lymphomas, in
      terms of diagnostic accuracy in prospective publications. A literature search was
      conducted in major databases and through manual review from the reference lists
      of articles that were recovered. The methodological quality of the selected items
      was evaluated using the QUADAS questionnaire. 9 publications were analyzed after
      the filtering process. The methodological quality of the same was broadly
      acceptable. In patients with LH, the negative predictive value of FDG-PET after 2
      3 cycles of chemotherapy, was ranged between 93.4% (95% CI, 92.6-94.3) and 100%
      (95% CI, 99.3-100%), and after the treatment, the negative predictive value of
      PET-FDG, was between 94.3% (95% CI, 92.8-95.7) and 100% (95% CI, 97.1-100). In
      patients with residual masses and LH, the meta-analysis of results showed a
      sensitivity of 100% (95% CI, 0.753-1) and a specificity of 84% (95% CI, 0.699
      0.934). PET-FDG seems to be a useful tool to evaluate the response to treatment
      of patients with lymphoma. However, it recommended further prospective studies
      and that possibly conducted in hybrid PET-CT scans, to determine its usefulness.

PMID- 19406049
TI  - [Peri-ictal SPECT in temporal lobe epilepsy: post-surgical evaluation].
AB  - INTRODUCTION: our aim was to evaluate the usefulness of peri-ictal SPECT in
      localising the epileptogenic region (ER) in candidates for temporal lobectomy to
      treat medically refractory complex partial seizures (CPS). Interictal and ictal
      SPECT, MRI and video-EEG results were compared and the positive predictive value
      (PPV) was calculated in those patients with good surgical outcome. MATERIALS AND
      METHODS: 37 patients who had a minimum of 3 years follow-up after surgery were
      studied retrospectively. Pre-surgical evaluation had included video-EEG
      monitoring, MRI and interictal and ictal SPECT. These results were compared to
      the surgically treated ER and successful outcome confirmed by post-surgical
      clinical follow-up. 29/37 patients remained seizure-free in the post-surgical
      follow-up. Interictal and peri-ictal SPECT were performed using 740 MBq of 99mTc
      HMPAO. Peri-ictal SPECT was ictal in 25 patients and postictal in 12. RESULTS: ER
      concordance with video-EEG and peri-ictal SPECT was 86% (32/37 patients). It was
      84% (31/37) for MRI and 54% (20/37 patients) for interictal SPECT. Peri-ictal
      SPECT localised the ER in 8/11 patients with discordant MRI and video-EEG
      results. Ictal SPECT localised the ER in the correct temporal lobe in 23/25
      patients (92% concordance). In the 29 patients with a good surgical outcome, the
      PPV of video-EEG was 95% (27/29) and it was 90% (26/29) for both MRI and peri
      ictal SPECT. CONCLUSIONS: peri-ictal brain SPECT is well able to localize ER in
      patients with temporal lobe epilepsy. Periictal SPECT concordance with ER was as
      good as video-EEG and MRI and its PPV was as good as that of MRI. We strongly
      recommend its use in the pre-surgical evaluation of temporal lobe epilepsy,
      especially when MRI and EEG are discordant.

PMID- 19406051
TI  - [Influence of temperature on the calibration curves in IRMA for neuron-specific
      enolase and its physicochemical interpretation].
AB  - BACKGROUND: immunoradiometric assay (IRMA) is one of the principal methods used
      for the analytical determination of neuron specific enolase (NSE) concentration.
      We studied the influence of temperature on the calibration curves obtained by
      this method, and a physicochemical justification based on two theoretical models
      is proposed. MATERIAL AND METHODS: we used a commercially available RIA kit for
      NSE and a gamma counter. Data was analysed using Statistical software. RESULTS
      AND DISCUSSION: activity bound to the antibody increases with temperature,
      producing results that are consistent with two modifications to the four
      parameter and Langmuir equations. CONCLUSIONS: the two models used successfully
      reproduce the results, with the adsorption model being preferable due to its
      greater simplicity and clearer physical significance.

PMID- 19406050
TI  - [The immunohistochemical expression of cyclin B1 is associated with higher SUV in
      18F-FDG-PET in non-small cell lung cancer patients. Initial results].
AB  - AIM: to study the expression of cyclin B1 and its possible relationship with the
      maximum SUV in FDG-PET and MIB1 expression in patients with NSCLC. MATERIALS AND
      METHODS: 49 patients (15 adenocarcinomas, 27 squamous cell carcinomas and 7
      bronchoalveolar carcinomas) were included in this study; the immunohistochemical
      expression of cyclin B1 was determined using the tissue-array technique. Each PET
      was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on
      an Advance system (GE) in 2D acquisition mode. RESULTS: cyclin B1 expression was
      detected in 40 out of 45 cases. The SUV values were higher (p=0.04) in the cyclin
      B1+ cases than in the negative cases (16.4+/-8.1 vs 10.9+/-6.2). Cyclin B1
      expression and SUV values were not correlated with the clinical stage. The
      expression of cyclin B1+ correlated positively (p<0.0001) with that of MIB1.
      After univariate analysis, only the cellular proliferation was a prognostic
      factor (p=0.037). CONCLUSIONS: our results suggest that there is a direct
      correlation between cyclin B1 expression and max-SUV values in the PET of NSCLC
      patients. When the association of cyclin B1 with positive MIB1 is also
      considered, our results support the role of cell proliferation in FDG uptake by
      the tumour.

PMID- 19406052
TI  - [Desmoid tumor of the thoraco-abdominal wall characterized with 18F
      fluorodeoxyglucose PET/ CT scan. Correlation with magnetic resonance and bone
      scintigraphy. Review of the literature].
AB  - Desmoid tumours are uncommon benign tumours but with aggressive behaviour,
      resulting from the proliferation of well-differentiated fibroblasts. Clinically,
      they present as a painless firm soft tissue mass. They can be solitary or
      multiple and have potential infiltrative capacity. When planning treatment, it is
      important to assess the correct tumour extent to permit curative radical surgery
      minimizing possible local recurrence. Different imaging techniques help to
      characterise these tumours. At present, magnetic resonance is the tool of choice
      for studying these tumours. The role of nuclear medicine techniques, such as bone
      scintigraphy, or more recently FDG-PET, has not been defined in the evaluation of
      these neoplasms. We present the case of a patient with a desmoid tumour of the
      abdominal-chest wall and we review the related literature.

PMID- 19406053
TI  - [Gallbladder cancer staging with 18F-FDG PET-CT].
AB  - Gallbladder cancer is the most common biliary tract neoplasm. It generally
      affects the elderly, who are usually clinically asymptomatic. When symptoms
      appear, they suggest the presence of complications locally or due to tumour
      progression. Late diagnosis of the disease indicates a poor prognosis for these
      patients. Surgery is the only treatment with curative intent, but it is only
      possible in the early stages. Diagnostic imaging of this type of tumour is
      usually performed with ultrasonography, computed tomography or magnetic resonance
      cholangiography. Positron emission tomography (PET) with fluorodeoxyglucose (FDG)
      with dedicated scanners or hybrid PET-CT scans are new diagnostic tools which
      could help in the pre-surgical diagnosis of these tumours. We present three cases
      to illustrate the usefulness of PET-FDG in the pre-surgical staging of
      gallbladder cancer.

PMID- 19406054
TI  - [Casual finding of a right-left shunt on ventilation/perfusion scintigraphy
      performed due to suspicion of pulmonary embolism].

PMID- 19406055
TI  - [Visualisation of prostate cancer liver metastases on a 99mTc-MDP bone scan].

PMID- 19406056
TI  - [111In-DTPAOC SPECT-CT in radiation pulmonary fibrosis].

PMID- 19406057
TI  - [Brain perfusion image with a portable mini-gamma camera (Sentinella) in brain
      death].

PMID- 19406059
TI  - Left radial approach in cardiac catheterization. Does it really matter?

PMID- 19406058
TI  - [Positron emission tomography/computed tomography with 18F-FDG. PET Working
      Group. Procedures Committee of the Spanish Society of Nuclear Medicine].

PMID- 19406060
TI  - Antithrombotic therapy for the prevention of reinfarction after reperfusion
      therapy: the price of success.

PMID- 19406061
TI  - New pharmacological options for patients with atrial fibrillation: the ATHENA
      trial.

PMID- 19406062
TI  - The left radial approach in daily practice. A randomized study comparing femoral
      and right and left radial approaches.
AB  - INTRODUCTION AND OBJECTIVES: The right radial (RR) approach has been incorporated
      into daily clinical practice as a valid alternative to the femoral (F) approach.
      The left radial (LR) approach is seldom used and few data are available from
      randomized studies comparing this approach with F and RR approaches. METHODS: We
      randomized 1005 consecutive patients referred to a tertiary-care hospital for
      cardiac catheterization to different approaches. Procedures were performed by
      three interventional cardiologists experienced in transradial catheterization.
      There were no exclusion criteria. The primary end-point was the percentage of
      procedures completed using the assigned approach. Secondary endpoints were the
      percentage completed in the absence of contraindications to any approach, the
      duration of the procedure, and the incidence of vascular complications. RESULTS:
      More procedures were completed with the F approach (LR, 71%; F, 92%; RR, 68%; P<
      .001). The success rate in the absence of contraindications to any approach
      (n=907) was greater with the F approach, with no difference between LR and RR
      approaches (LR, 80%; F, 96%; RR, 82%; P< .001). The canalization time was greater
      with the LR approach (P< .001), the time required for diagnosis was shorter with
      the F approach (P< .001) and compression was faster with the radial approach (P<
      .001). There was no difference in the total duration of diagnostic procedures
      (P=.22) or interventions (P=.9). The incidence of vascular complications was
      lower with the radial approach (P=.03). CONCLUSIONS: The left radial approach is
      as valid an alternative to the femoral approach as the right radial approach.

PMID- 19406063
TI  - Comparison of medium-term outcomes obtained with drug-eluting stents and coronary
      artery bypass grafts in an unselected population of diabetic patients with
      multivessel coronary disease. Propensity score analysis.
AB  - INTRODUCTION AND OBJECTIVES: Since the introduction of drug-eluting stents, the
      optimum revascularization strategy in diabetic patients with multivessel coronary
      disease has remained controversial. METHODS: This study used multivariate
      logistic regression analysis and propensity score matching to compare results in
      270 consecutive diabetic patients (2000-2004) with multivessel disease (> or =2
      vessels with a >70% de novo stenosis involving the proximal left anterior
      descending coronary artery) who underwent either coronary artery bypass grafting
      (CABG; n=142) or implantation of a drug-eluting stent (DES; i.e. rapamycin or
      paclitaxel; n=128). The following clinical outcomes (i.e. major adverse cardiac
      or cerebrovascular events [MACCEs]) were assessed: death, nonfatal myocardial
      infarction (MI), stroke and repeat revascularization at 2 years. RESULTS:
      Patients who received DESs were older (67.5+/-7 years vs. 65.3+/-8 years; P=.05)
      and more often had a previous MI (49.2% vs. 28.2%; P< .01), but no more often had
      a depressed left ventricular ejection fraction < or =45% (32.4% vs. 28.1%).
      Coronary anatomy was more complex in surgical patients (SYNTAX score, 25.9+/-7
      vs. 18.5+/-6; P< .001) and the quality of revascularization was better (i.e.
      anatomically complete revascularization: 52.8% vs. 28.1%; P< .01). The incidence
      of MACCEs was 18.7% in the CABG group and 21.8% in the DES group (adjusted odds
      ratio [OR] = 0.93; 95% confidence interval [CI], 0.47-1.86). The composite
      endpoint of death, MI or stroke occurred in 15.8% undergoing CABG and 12.9%
      receiving a DES (adjusted OR = 1.19; 95% CI, 0.72-1.88). There was less need for
      revascularization in CABG patients (4.3% vs. 12.1%; adjusted OR = 0.42; 95% CI,
      0.16-1.14; P=.09). CONCLUSIONS: In an unselected population of diabetic patients
      with multivessel coronary disease, the principle advantage of CABG was the
      reduced need for revascularization. There was no difference in the rate of death,
      MI or stroke.

PMID- 19406064
TI  - In-hospital outcomes associated with fibrinolytic and thienopyridine use in
      patients with ST-segment elevation acute myocardial infarction. The global
      registry of acute coronary events.
AB  - INTRODUCTION AND OBJECTIVES: To investigate how thienopyridine treatment, with or
      without associated fibrinolysis, affects the rates of major bleeding and
      inhospital death in patients with ST-elevation myocardial infarction (STEMI).
      METHODS: The rates of major bleeding and in-hospital death were studied in 14,259
      consecutive patients with STEMI. During hospitalization, 5340 (38%) received
      thienopyridines, 3007 (21%) received fibrinolytic drugs, and 2044 (14%) received
      both. RESULTS: Major bleeding occurred more frequently in patients who received
      thienopyridines with or without fibrinolytics, in 4.6% and 4.1%, respectively,
      compared with 2.3% in those who received fibrinolytics alone and 2.8% in those
      who received neither (P< .001). Multivariate analysis, which included adjustments
      for risk factors for bleeding, percutaneous coronary intervention and cardiac
      catheterization, showed that thienopyridine treatment was an independent risk
      factor for bleeding (odds ratio=1.68; 95% confidence interval, 1.23-2.31). In
      hospital mortality was lower in patients who received a thienopyridine, and such
      treatment was an independent predictor of lower mortality (odds ratio=0.50; 95%
      confidence interval, 0.39-0.60). CONCLUSIONS: Thienopyridine treatment was
      associated with an increased risk of major bleeding but also with a better in
      hospital prognosis. These findings in unselected patients with STEMI, who are
      representative of those seen in daily clinical practice, complement, but do not
      replace, the data obtained in randomized clinical trails of selected patients.

PMID- 19406065
TI  - Cystatin C provides more information than other renal function parameters for
      stratifying risk in patients with acute coronary syndrome.
AB  - INTRODUCTION AND OBJECTIVES: The protein cystatin C has a stable plasma
      concentration and is eliminated exclusively by the kidneys. The aim of this study
      was to determine the prognostic value of cystatin C in patients with acute
      coronary syndrome (ACS). METHODS: The prospective study included 203 hospitalized
      ACS patients. Clinical evaluation during the first 24 hours of hospitalization
      included a hemogram and measurement of creatinine, cystatin C, total and
      fractionated cholesterol and markers of myocardial necrosis. The glomerular
      filtration rate (GFR) was estimated using the MDRD (Modification of Diet in Renal
      Disease) equation. A comparison was made between two groups of patients divided
      according to a serum cystatin-C level above or below 0.95 mg/L. The mean follow
      up period was 151 days. RESULTS: In total, 90 patients (44.3%) had a cystatin-C
      level < or =0.95 mg/L and 113 (55.7%) had a level >0.95 mg/L. Those with a
      cystatin-C level >0.95 mg/L had poorer in-hospital outcomes, including more
      frequent heart failure (51.3% vs. 13.3%; P=.001) and higher in-hospital mortality
      (17.6% vs. 3.3%; P=.001), as well as higher mortality throughout follow-up (22.0%
      vs. 5.6%; P=.001). Multivariate analysis adjusted for age, ejection fraction and
      troponin-I and high-sensitivity C-reactive protein concentrations showed that
      cystatin C was the most powerful independent predictor of a cardiovascular event
      (relative risk=1.91; 95% confidence interval, 1.03-3.53). Patients with a GFR >60
      mL/1.73 m(2) and a cystatin-C level >0.95 mg/L had higher in-hospital mortality
      (10.2% vs. 3.9%; P=.001). CONCLUSIONS: Measurement of cystatin C in high-risk ACS
      patients may be clinically useful for risk stratification during hospitalization,
      particularly in those with a normal GFR.

PMID- 19406066
TI  - Clinical outcomes with off-pump coronary surgery after angioplasty with stent.
AB  - INTRODUCTION AND OBJECTIVES: The aim was to determine whether prior coronary
      stent implantation affects postoperative outcomes in patients undergoing coronary
      artery bypass grafting. METHODS: Between January 2005 and April 2008, a
      retrospective analysis was carried out to evaluate the effect of prior coronary
      stent implantation in patients undergoing off-pump coronary surgery on the
      incidence of major cardiovascular events in the postoperative period (i.e. at 30
      days or during postoperative hospitalization). RESULTS: In total, 796 consecutive
      patients underwent coronary artery bypass grafting. Of these, 116 (14.6%) had a
      coronary stent at the time of surgery. Patients with and without stents had
      similar levels of risk (i.e. EuroSCORE). Multivariate analysis, adjusted for the
      presence of confounding variables (i.e. preoperative left ventricular ejection
      fraction <40%, critical preoperative state, age, history of cerebrovascular
      accident, recent acute myocardial infarction, number of diseased coronary
      vessels, incomplete revascularization and on-pump conversion), showed that the
      presence of a stent was significantly associated with increased risks of
      postoperative myocardial infarction (relative risk [RR]=3.13; 95% confidence
      interval [CI], 1.75-5.96), in-hospital cardiac mortality (RR=4.62; 95% CI, 1.76
      12.11) and in-hospital all-cause mortality (RR=3.65; 95% CI, 1.60-8.34).
      CONCLUSIONS: In our experience, coronary artery stent implantation prior to
      coronary surgery was associated with increased risks of postoperative myocardial
      infarction, cardiac mortality and all-cause mortality in the postoperative
      period.

PMID- 19406067
TI  - Mortality risk in spanish adults with diagnosed diabetes, undiagnosed diabetes or
      pre-diabetes. The Asturias study 1998-2004.
AB  - INTRODUCTION AND OBJECTIVES: Although type-2 diabetes is a well-known cause of
      death, the mortality associated with undiagnosed diabetes and early-stage
      dysglycemia has not been clearly determined. METHODS: This study included 1015
      individuals aged 30-75 years who took part in the first phase of the Asturias
      study (1998-1999). Participants completed a questionnaire and underwent a
      physical examination and an oral glucose tolerance test (OGTT). All deaths that
      occurred in the cohort within 6 years of follow-up (i.e. December 1998 to
      December 2004) were recorded. RESULTS: Participants were divided into four groups
      according to the condition indicated by their OGTT result in the first phase of
      the study: normoglycemia, pre-diabetes, undiagnosed diabetes or diagnosed
      diabetes (World Health Organization 1999 criteria). A total of 42 deaths were
      recorded during follow-up. With normoglycemic individuals acting as a control
      group, multivariate analysis showed that the relative risk of mortality was 2.5
      (95% CI, 1-6.3) in the group with diagnosed diabetes, 2.7 (95% CI, 1.1-6.7) in
      the group with undiagnosed diabetes and 1.6 (95% CI, 0.7-4) in the group with pre
      diabetes. CONCLUSIONS: Both individuals with diagnosed diabetes and those with
      undiagnosed diabetes had a risk of mortality around 2.5-3 times greater than
      individuals with normoglycemia. Those with pre-diabetes also had increased
      mortality relative to the control group, though the difference was not
      significant.

PMID- 19406068
TI  - Quantitative analysis of left ventricular function as a tool in clinical
      research. Theoretical basis and methodology.
AB  - The usefulness the left ventricular ejection fraction as a surrogate endpoint in
      clinical trials has been confirmed by numerous studies. However, if this approach
      is to be applied successfully, images must be acquired in a rigorously controlled
      manner, and it is advisable to use measurement units that have been specifically
      developed for quantitative analysis of the imaging parameters obtained with
      current imaging techniques. This review summarizes what is now known about the
      left ventricular ejection fraction and left ventricular volumes, discusses the
      importance of measurement units in image analysis, and describes the different
      imaging techniques available. Finally, there is a discussion of how to select the
      best imaging technique for specific clinical applications.

PMID- 19406069
TI  - Molecular basis of leukocyte-endothelium interactions during the inflammatory
      response.
AB  - The process of leukocyte extravasation, a critical step in the inflammatory
      response, involves the migration of leukocytes from the bloodstream towards
      target tissues, where they exert their effector function. Leukocyte extravasation
      is orchestrated by the combined action of cellular adhesion receptors and
      chemotactic factors, and involves radical morphological changes in both
      leukocytes and endothelial cells. Thus, it constitutes an active process for both
      cell types and promotes the rapid and efficient influx of leukocytes to
      inflammatory foci without compromising the integrity of the endothelial barrier.
      This article provides a review of leukocyte extravasation from both molecular and
      mechanical points of view, with a particular emphasis on the most recent findings
      on the topic. It includes a description of newly revealed steps in the adhesion
      cascade, such as slow rolling motion, intraluminal crawling and alternative
      pathways for transcellular migration, and discusses the functional role of novel
      adhesion receptors, the spatiotemporal organization of receptors at the plasma
      membrane and the signaling pathways that control different phases of the
      extravasation process.

PMID- 19406070
TI  - Image in cardiology. Pulmonary vein isolation and sinus rhythm.

PMID- 19406071
TI  - Cardiac monitoring in stroke units: importance of diagnosing atrial fibrillation
      in acute ischemic stroke.
AB  - In patients with stroke, atrial fibrillation is an independent risk factor and
      indicates a poor prognosis. Cardiac monitoring is carried out for longer periods
      in stroke units. The aim of this study was to determine the frequency at which
      atrial fibrillation is detected in stroke units and the percentage of patients
      with acute ischemic stroke or transient ischemic attack who receive anticoagulant
      therapy. The study included 465 patients, who were monitored in a stroke unit for
      an average of 54.55+/-35.74 h. Atrial fibrillation was detected in 33 (48.5% had
      paroxysmal atrial fibrillation and 51.5% had persistent atrial fibrillation). The
      most common risk factor was hypertension. Anticoagulation therapy was started in
      57.5%. In conclusion, use of cardiac monitoring in a stroke unit was useful for
      detecting atrial fibrillation in patients with acute stroke and resulted in
      treatment modification in more than half the affected patients.

PMID- 19406072
TI  - Knowledge of correct blood pressure measurement procedures among medical and
      nursing students.
AB  - This study reports on the level of knowledge about correct blood pressure (BP)
      measurement procedures among 175 third-year and 176 sixth-year students at a
      medical faculty and 58 third-year students at a nursing college. Only 51.8% of
      all students thought that they knew how to measure BP correctly (28.6% in the
      third year and 61.9% in the sixth year at the medical faculty and 91.4% at the
      nursing college). Among sixth-year medical students, 12.5% knew the appropriate
      cuff size, 35% that the stethoscope diaphragm should not be placed under the
      cuff, and 43% that the cuff deflation rate affects BP measurement. Among nursing
      students, 33% knew the appropriate cuff size, 22% that an outpatient's BP should
      be measured more than once during each visit, and 55% that a diagnosis of
      hypertension can only be made if the BP is elevated on more than one visit.

PMID- 19406073
TI  - A homozygous MYBPC3 gene mutation associated with a severe phenotype and a high
      risk of sudden death in a family with hypertrophic cardiomyopathy.
AB  - Genetic studies can play a key role in the comprehensive evaluation of familiar
      hypertrophic cardiomyopathy and in the development of individualized medicine.
      Although only a few cases have been described, there exists a group of patients
      with complex genotypes that are associated with severe disease manifestations and
      a high risk of sudden death. We describe a family in which some members
      experienced the early development of systolic and diastolic dysfunction while
      others experienced sudden death at a young age. We identified a novel homozygous
      mutation (IVS6+5G>A) in the myosin-binding protein-C gene that explained the
      phenotype of affected individuals and that enabled us to estimate the risk in
      other family members and to offer genetic counseling.

PMID- 19406074
TI  - Thrombosis of an apparently normal thoracic aorta: another case, another
      conundrum.

PMID- 19406075
TI  - Ivabradine as a treatment option for inappropriate sinus tachycardia.

PMID- 19406077
TI  - Thrombectomy after failed fibrinolysis in prosthetic tricuspid valve thrombosis.

PMID- 19406076
TI  - Long-duration self-limiting idiopathic ventricular fibrillation.

PMID- 19406078
TI  - Myocardial infarction and intraventricular thrombosis masked by acute
      myopericarditis in a patient with thrombocytosis.

PMID- 19406079
TI  - Essential thrombocythemia and acute myocardial infarction.

PMID- 19406080
TI  - Optical coherence tomography after rotational atherectomy.

PMID- 19406081
TI  - Coronary artery dissection assessed by optical coherence tomography.

PMID- 19406082
TI  - [Survival of rats subjected to different levels of pulmonary injury].
AB  - OBJECTIVE: To determine a pulmonary injury model in rats that is associated with
      moderate mortality after extubation. DESIGN AND SETTING: An experimental study in
      an animal model of ventilator-induced lung injury in the animal research
      laboratory in Virgen de las Nieves University Hospital. SUBJECTS AND METHOD: A
      total of 45 male Wistar-Kyoto rats weighing 250-300g received food and water ad
      libitum. The rats were anesthetized and a tracheotomy was performed by insertion
      of endotracheal tube by tracheotomy. INTERVENTIONS: Pulmonary injury due to
      mechanical ventilation was maintained for 60 min with high tidal volume (25
      ml/kg) combined with intratracheal instillation of different doses of 0,9% saline
      solution. Rats were randomly distributed into 3 groups (15 animals in each group)
      with different amounts of instilled saline solution: group I, 0.5 ml/250 g body
      weight; group II, 1 ml/250 g body weight, and group III, 1.5 ml/250 g body
      weight. MAIN MEASUREMENTS: Survival of animals after extubation was recorded
      every 5 min for the first 40 min and then at 3 h, 24 h, 72 h, and 7 days.
      RESULTS: Survival in rats that received 0.5, 1 and 1.5 ml/250 g of intratracheal
      saline solution was 60%, 43% and 0% respectively, with statistically significant
      differences between groups receiving 0.5 and 1.5 ml/250 g (p = 0.003).
      CONCLUSIONS: Survival in rats mechanically ventilated with high moderate volume
      is influenced by increased doses of intratracheal saline solution and this is
      important to design studies that analyze the effect the interventions on
      mortality.

PMID- 19406084
TI  - [Variations in health-related quality of life in critical patients].
AB  - OBJECTIVE: To determine the changes in the health-related quality of life (hRQOL)
      six months after discharge from the ICU and the conditions associated to them.
      DESIGN: A prospective cohort study. SETTING: 14 beds medical-surgical intensive
      care unit (ICU). PATIENTS: A total of 247 patients admitted to our ICU for more
      than 24 hours with a follow-up of 6 months were study. Those admitted with acute
      coronary syndrome or for monitoring purposes were excluded. INTERVENTION: A
      quality of life survey was conducted using the score developed by the PAEEC group
      (project of the epidemiological analysis of critical illness) to assess hRQOL
      before ICU admission and 6 months after discharge. RESULTS: The hRQOL
      deteriorated, going from a median value of 3 to 6 (p < 0.001). The multivariate
      analysis showed less deterioration of hRQOL in patients with chronic health
      conditions registered on the APAChE-II score (regression coefficient [RC] = -1.4;
      95% CI, -2.5 to -0.2; p < 0.02) and in those with a hRQOL > or = 10 points (RC = 
      4,4; 95% CI, -5.9 to -2.8; p < 0.001). There was more deterioration in
      polytraumatized patients (RC = 1.9; 95% CI, 0.6-3.3; p = 0.01) or with renal
      failure (RC = 3.9; 95% CI, 1.9-5.9; p < 0.001) or in those with a stay duration
      longer than 10 days (RC = 1.9; 95% CI, 0.6-3.2; p < 0.001). CONCLUSIONS: Most
      patients experience deterioration of hRQOL. Patients with chronic diseases or
      with worst previous hRQOL who survive 6 months experience less deterioration of
      hRQOL than those who are polytraumatized or have renal failure or a longer ICU
      stay.

PMID- 19406083
TI  - [Percutaneous tracheotomy and cricothyroidotomy in the critical patient].
AB  - OBJECTIVE: To review and compare the complications of percutaneous tracheotomy
      (TP) and cricothyroidotomy (CT) used to perform tracheal intubation in patients
      requiring prolonged mechanical ventilation. DESIGN: A prospective, observational
      study performed from October 2004 to October 2006, and follow-up of course until
      May 2007. SETTING: Intensive care service from a university-affiliated teaching
      hospital. PATIENTS: A total of 82 patients in which CT or TP were necessary.
      Forty-three TP and 39 CT were performed. MAIN MEASUREMENTS: Reason for TP or CT,
      demographic data, severity scores, ICU length of stay, orotracheal intubation
      (OTI) days, CT/TP early and late complications and in-hospital evolution were
      collected. RESULTS: TP/CT were performed due to prolonged ventilation in 62 (76%)
      patients and because of impaired neurological status in the remaining patients.
      There were no differences between TP/CT in gender, APACHE II, ICU length of stay,
      previous OTI days. Patients in the CT group were older (68 +/- 9 vs 54 +/- 15
      years, p < 0.001). There were 5 mild adverse events (3 guide angulations and 2
      lateral tracheal punctions) after TP, and 1 severe adverse event (pulmonary
      ventilation problem) after CT. There were no fatal event related with TP/CT.
      Thirty-four patients were decanulated. Mild local injuries were seen in 8
      patients (6 TP vs 2 CT). Only 1 subglottic granuloma was seen late in CT group.
      CONCLUSIONS: In our experience CT constitutes a safety and feasible alternative
      to TP when TP is counter-indicated.

PMID- 19406085
TI  - [Neuromuscular abnormalities in critical illness].
AB  - The spectrum of neuromuscular disease encountered in today's intensive care units
      (ICU) has evolved over the last few decades. However, in spite of many studies on
      neuromuscular disorders complicating critical illness as well as its
      epidemiology, etiology, treatment and prognosis, several key areas remain
      unclear. Two main groups are found among these neuromuscular abnormalities. The
      first group includes primary neuromuscular disorders present on admission to the
      ICU in which a possible etiology can be identified. Guillain-Barre syndrome and
      myasthenia gravis are two of the most common diseases admitted to ours units. In
      the second group, weakness is acquired in the ICU in the absence of preexisting
      neuromuscular disease. It is believed to reflect illnesses or treatments
      occurring in the ICU. Critical illness polyneuropathy (CIP) is the most clearly
      defined neuromuscular complication in this group. However, although we have
      better knowledge of its clinical, diagnosis, and prognosis features, its
      pathophysiological substrate has not been fully elucidated. Neuromuscular
      junction defects and specially myopathies, that frequently coexist with CIP, are
      the others main causes of acquired weakness in critically ill patients. Advances
      in understanding of these neuromuscular disorders could have an important impact
      in terms of developing effective preventive and therapeutic interventions that
      could help to improve the poor prognosis of these patients.

PMID- 19406086
TI  - [Utility of recruitment maneuvers (pro)].
AB  - In recent years lung recruitment maneuvers (RM) have awakened an increasing
      interest due to their potential beneficial effects in lung protection so that
      they have been progressively introduced into clinical practice. Many clinical and
      experimental studies have described the physiological benefits obtained after
      lung re-expansion although these benefits are not uniform, partly because of the
      wide heterogeneity of the RMs applied and lack of criteria defining their goal.
      Therefore, to date it has been difficult to establish the role of recruitment in
      the ventilatory management of ARDS patients. However, the information obtained
      from recent studies has improved our understanding regarding the mechanisms
      governing lung recruitment, interpretation of its response and its side effects
      and this has strongly contributed to its improved practical application. Lung
      recruitment must be applied in a protocolized and individualized way,
      establishing the pressure necessary to obtain the reasonably possible maximum
      lung re-expansion in each patient. Post RM PEEP adjustment is an essential aspect
      which, if ignored, renders RM useless and possibly without indication. Taking
      these essential aspects into account we are getting closer to, as the author
      believes, finally demonstrating the benefit of RM in lung protection and ARDS
      patients' outcome.

PMID- 19406087
TI  - [Utility of recruitment maneuvers (con)].
AB  - A reduction in both total lung volume and in lung parenchyma useful for gas
      exchange has been observed in ARDS patients. Applying an appropriate ventilatory
      pattern that includes PEEP can open up collapsed areas of the lung to aeration,
      thus ensuring a more homogeneous distribution of air in the lung. However, the
      heterogeneous patterns observed in patients with ARDS vary widely in their
      response to ventilation with PEEP. Recruitment maneuvers (RM) have been proposed
      as an adjuvant treatment to mechanical ventilation to re-expand collapsed lung
      tissue in ARDS. Nevertheless, it is unclear whether RM are useful when patients
      are ventilated with high PEEP or when they have fibrosis, stiff chest wall, or
      hypovolemia, among other conditions. Likewise, decisions about RM must take into
      account not only their short- and long-term efficacy and reversibility, but also
      possible adverse effects derived from the high pressures reached during RM,
      including barotrauma, hemodynamic alterations, reduced systolic volume and aortic
      flow, and difficulties in venous return, as well as the possibility of bacterial
      translocation to the bloodstream or other organs. This article review the effects
      of RM as adjuvant treatment to mechanical ventilation in ARDS patients and
      discuss its efficacy and potential benefits as well as the different interactions
      that RM can have with the diverse conditions that can be associated to ARDS.

PMID- 19406088
TI  - [Clinical, epidemiological and taxonomic aspects of systemic candidiasis in an
      intensive care unit].
AB  - The clinical and epidemiological profile and survival of patients admitted into
      our intensive care unit (ICU) was analyzed. A retrospective-prospective case
      series from 2002 to 2004 and 2005 to 2006, respectively, of patients diagnosed
      with systemic candidiasis in an ICU in a tertiary hospital was studied. Twenty
      six cases with systemic candidiasis were included (75% of the cases were male).
      These subjects underwent multiple vascular or drainage interventions and had a
      prolonged length of stay in ICU. The first motive to enter ICU was sepsis.
      Candida albicans (CA) was isolated in 53.8% of cases versus 46.2% for other
      Candidae (CNA). Over the last years, we have observed a progressively higher
      incidence for CNA (p = 0.02). We registered an especially high mortality rate
      (42%), that is higher in the CA group. <<Sevilla Score>> defined the mortality in
      the progressive risk groups (p = 0.026).

PMID- 19406089
TI  - [Recurrent pulmonary edema in a patient with intracranial bleeding. A case
      report].

PMID- 19406090
TI  - [In the intensive medicine services, informed consent should be requested for non
      urgent transfusion].

PMID- 19406091
TI  - [Future perspectives for clinical autopsy in patients from critic and urgent care
      units].

PMID- 19406092
TI  - [Cardiac tamponade for massive pericardial effusion secondary to primary
      hypothyroidism].

PMID- 19406094
TI  - A quantitative stopped-flow fluorescence assay for measuring polymerase
      elongation rates.
AB  - The measurement of nucleic acid polymerase elongation rates is often done via a
      lengthy experimental process involving radiolabeled substrates, quenched
      elongation experiments, electrophoretic product separation, and band
      quantitation. In this work, we describe an alternative real-time stopped-flow
      assay for obtaining kinetic parameters for elongation of extended sequences. The
      assay builds on our earlier PETE (polymerase elongation template element) assay
      designed for high-throughput screening purposes [S.P. Mestas, A.J. Sholders, O.B.
      Peersen, A fluorescence polarization-based screening assay for nucleic acid
      polymerase elongation activity, Anal. Biochem. 365 (2007) 194-200] and relies on
      measuring how long it takes a polymerase to reach the end of a defined length
      template. Using poliovirus polymerase and self-priming hairpin RNA substrates
      with 6- to 26-nt-long templating regions, we demonstrate that the assay can be
      used to determine V(max) rates for elongation and apparent K(m) values for
      nucleotide triphosphate (NTP) use. Modeling the reaction kinetics as a series of
      irreversible steps allows us to numerically fit the entire time-based dataset by
      properly accounting for the temporal distribution of intermediate species. This
      enables us to determine average elongation rates over heterogeneous templating
      regions that mimic viral genome substrates. The assay is easily extendable to
      other RNA and DNA polymerases, can accommodate secondary structures in the
      template, and can in principle be used for any enzyme traversing along an
      extended substrate.

PMID- 19406095
TI  - Comparative analysis of human saliva microbiome diversity by barcoded
      pyrosequencing and cloning approaches.
AB  - Metagenomic studies traditionally rely on cloning polymerase chain reaction (PCR)
      products and sequencing multiple clones. However, this approach is tedious and
      expensive, thereby limiting the range and scale of questions that can be
      addressed. Recent developments in DNA sequencing technologies enable a dramatic
      increase in throughput via parallel in-depth analysis of many samples with
      limited sample processing and lower costs. We directly compared the traditional
      cloning approach with a barcoded pyrosequencing method to see whether the latter
      accurately describes microbiome diversity in human saliva. Our results indicate
      that despite the shorter read lengths, the pyrosequencing approach provides a
      description of the human salivary microbiome that is in good agreement with
      results based on the traditional cloning and sequencing approach.

PMID- 19406093
TI  - Changing patterns of West Nile virus transmission: altered vector competence and
      host susceptibility.
AB  - West Nile virus (WNV) is a flavivirus (Flaviviridae) transmitted between Culex
      spp. mosquitoes and avian hosts. The virus has dramatically expanded its
      geographic range in the past ten years. Increases in global commerce, climate
      change, ecological factors and the emergence of novel viral genotypes likely play
      significant roles in the emergence of this virus; however, the exact mechanism
      and relative importance of each is uncertain. Previously WNV was primarily
      associated with febrile illness of children in endemic areas, but it was
      identified as a cause of neurological disease in humans in 1994. This modulation
      in disease presentation could be the result of the emergence of a more virulent
      genotype as well as the progression of the virus into areas in which the age
      structure of immunologically naive individuals makes them more susceptible to
      severe neurological disease. Since its introduction to North America in 1999, a
      novel WNV genotype has been identified that has been demonstrated to disseminate
      more rapidly and with greater efficiency at elevated temperatures than the
      originally introduced strain, indicating the potential importance of temperature
      as a selective criteria for the emergence of WNV genotypes with increased
      vectorial capacity. Even prior to the North American introduction, a mutation
      associated with increased replication in avian hosts, identified to be under
      adaptive evolutionary pressure, has been identified, indicating that adaptation
      for increased replication within vertebrate hosts could play a role in increased
      transmission efficiency. Although stable in its evolutionary structure, WNV has
      demonstrated the capacity for rapidly adapting to both vertebrate hosts and
      invertebrate vectors and will likely continue to exploit novel ecological niches
      as it adapts to novel transmission foci.

PMID- 19406096
TI  - Extraction of RNA from Ca-alginate-encapsulated yeast for transcriptional
      profiling.
AB  - We have developed a method for preparing high-quality total RNA from Ca-alginate
      encapsulated Saccharomyces cerevisiae that is suitable for microarray analysis.
      Encapsulated cells were harvested from immobilized cell reactors and flash-frozen
      in liquid nitrogen. Following low-temperature mechanical disruption, cells were
      freed from Ca-alginate by reverse ionotropic gelation and purified by
      centrifugation, and then total RNA was extracted using hot acid phenol. The yield
      and quality of the RNA were consistently high; the RNA was free of contaminating
      alginate, and in microarray analysis it performed as well as RNA isolated from
      planktonic cells.

PMID- 19406097
TI  - Evaluating the utility of the HTRF Transcreener ADP assay technology: a
      comparison with the standard HTRF assay technology.
AB  - The HTRF (homogeneous time-resolved fluorescence) Transcreener ADP assay is a new
      kinase assay technology marketed by Cis-Bio International (Bagnols-Ceze, France).
      It measures kinase activity by detecting the formation of ADP using a monoclonal
      antibody and HTRF detection principles. In this article, we compare this
      technology with a standard HTRF kinase assay using EGFR [L858R/T790M] mutant
      enzyme as a case study. We demonstrate that the HTRF Transcreener ADP assay
      generated similar kinetic constants and inhibitor potency compared with the
      standard HTRF assay. However, the smaller dynamic window and lower Z' factor of
      the HTRF Transcreener ADP assay make this format less preferable for high
      throughput screening. Based on the assay principle, the HTRF Transcreener ADP
      assay can detect both kinase and ATPase activities simultaneously. The ability to
      probe ATPase activity opens up new avenues for assaying kinases with intrinsic
      ATPase activity without the need to identify substrates, and this can speed up
      the drug discovery process. However, caution must be exercised because any
      contaminating ATPase activity will result in an invalid assay. The inability to
      tolerate high concentrations of ATP in the assay will also limit the application
      of this technology, especially in compound mechanistic studies such as ATP
      competition. Overall, the HTRF Transcreener ADP assay provides a new alternative
      tool to complement existing assay technologies for drug discovery.

PMID- 19406098
TI  - Mechanism and energetics by which glutamic acid 242 prevents leaks in cytochrome
      c oxidase.
AB  - Cytochrome c oxidase (CcO) is the terminal enzyme of aerobic respiration. The
      energy released from the reduction of molecular oxygen to water is used to pump
      protons across the mitochondrial or bacterial membrane. The pump function
      introduces a mechanistic requirement of a valve that prevents protons from
      flowing backwards during the process. It was recently found that Glu-242, a key
      amino acid in transferring protons to be pumped across the membrane and to the
      site of oxygen reduction, fulfils the function of such a valve by preventing
      simultaneous contact to the pump site and to the proton-conducting D-channel
      (Kaila V.R.I. et al. Proc. Natl. Acad. Sci. USA 105, 2008). Here we have
      incorporated the valve model into the framework of the reaction mechanism. The
      function of the Glu valve is studied by exploring how the redox state of the
      surrounding metal centers, dielectric effects, and membrane potential, affects
      the energetics and leaks of this valve. Parallels are drawn between the dynamics
      of Glu-242 and the long-standing obscure difference between the metastable O(H)
      and stable O states of the binuclear center. Our model provides a suggestion for
      why reduction of the former state is coupled to proton translocation while
      reduction of the latter is not.

PMID- 19406099
TI  - The multiple roles of light-harvesting chlorophyll a/b-protein complexes define
      structure and optimize function of Arabidopsis chloroplasts: a study using two
      chlorophyll b-less mutants.
AB  - The multiple roles of light-harvesting chlorophyll a/b-protein complexes in the
      structure and function of Arabidopsis chloroplasts were investigated using two
      chlorophyll b-less mutants grown under metal halide lamps with a significant far
      red component. In ch1-3, all six light-harvesting proteins of photosystem (PS) II
      were greatly decreased; in ch1-3lhcb5, Lhcb5 was completely absent while the
      other five proteins were further decreased. The thylakoids of ch1-3 were less
      negatively-charged than the wild type, and those of ch1-3lhcb5 were even less so.
      Despite the expected weaker electrostatic repulsion, however, thylakoids in
      leaves of the mutants were not well stacked, an effect we attribute to lower van
      der Waals attraction, lower electrostatic attraction between opposite charges,
      and the absence or instability of PSII supercomplexes and peripheral light
      harvesting trimers. The quantum yield of oxygen evolution in leaves decreased
      from 0.109 (wild type) to 0.087 (ch1-3) and 0.081 (ch1-3lhcb5) O(2) (photon
      absorbed)(-1); we attribute this decrease to an excessive spillover from PSII to
      PSI, a limited PSII antenna, and increased light-independent thermal dissipation
      in PSII in the mutants. Destabilization of the donor side of PSII, indicated by
      slower electron donation to the redox-active tyrosine Y(Z)(*) in ch1-3, probably
      enhanced PSII susceptibility to photoinactivation, increased the non-functional
      PSII complexes in vivo, and further inactivated PSII complexes in vitro. The
      evolution of chlorophyll b-containing chloroplasts seems to fine-tune oxygenic
      photosynthesis.

PMID- 19406101
TI  - dXNP/DATRX increases apoptosis via the JNK and dFOXO pathway in Drosophila
      neurons.
AB  - Mutation of the XNP/ATRX gene, which encodes an SNF2 family ATPase/helicase
      protein, leads to ATR-X syndrome and several other X-linked mental retardation
      syndromes. Although XNP/ATRX is a chromatin remodeler, the molecular mechanism by
      which mental retardation occurs in patients with ATR-X has yet to be determined.
      To better understand the role of XNP/ATRX in neuronal development, we expressed
      Drosophila XNP (dXNP/DATRX) ectopically in Drosophila neurons. Neuronal
      expression of dXNP/DATRX resulted in various developmental defects and induced
      strong apoptosis. These defects and apoptosis were suppressed by Drosophila
      inhibitor of apoptosis protein 1. Expression of dXNP/DATRX also increased JNK
      activity and the levels of reaper and hid transcripts, which are pro-apoptotic
      factors that activate caspase. Furthermore, dXNP/DATRX-induced rough eye
      phenotype and apoptosis were suppressed by dFOXO deficiency. These results
      suggest that dXNP/DATRX is involved in caspase-dependent apoptosis in Drosophila
      neurons via regulation of the JNK and dFOXO pathway.

PMID- 19406102
TI  - TNF superfamily member, TL1A, is a potential mucosal vaccine adjuvant.
AB  - The identification of cytokine adjuvants capable of inducing an efficient mucosal
      immune response against viral pathogens has been long anticipated. Here, we
      attempted to identify the potential of tumor necrosis factor superfamily (TNFS)
      cytokines to function as mucosal vaccine adjuvants. Sixteen different TNFS
      cytokines were used to screen mucosal vaccine adjuvants, after which their immune
      responses were compared. Among the TNFS cytokines, intranasal immunization with
      OVA plus APRIL, TL1A, and TNF-alpha exhibited stronger immune response than those
      immunized with OVA alone. TL1A induced the strongest immune response and
      augmented OVA-specific IgG and IgA responses in serum and mucosal compartments,
      respectively. The OVA-specific immune response of TL1A was characterized by high
      levels of serum IgG1 and increased production of IL-4 and IL-5 from splenocytes
      of immunized mice, suggesting that TL1A might induce Th2-type responses. These
      findings indicate that TL1A has the most potential as a mucosal adjuvant among
      the TNFS cytokines.

PMID- 19406103
TI  - Lysosomal exocytosis: an important event during invasion of lamp deficient cells
      by extracellular amastigotes of Trypanosoma cruzi.
AB  - Trypanosoma cruzi is an obligate intracellular organism in vertebrate hosts.
      Lysosomes are involved in parasite invasion. LAMP-1 and LAMP-2 are the most
      abundant glycoproteins of the lysosomal membrane. This study is the first report
      on the invasion of T. cruzi extracellular amastigotes (EA) in single LAMP-1 or
      LAMP-2 knockouts, respectively, or in two independent LAMP-1/2 double-knockout
      cell lines. When compared to their respective wild type clones, the EA show
      higher infectivity in LAMP-2 knockouts, but no difference was seen in LAMP-1
      knockout cells. Similarly, EA invasion rate was higher for one of the double
      knockout clones but not for the other. Higher lysosomal exocytosis correlated
      with a higher invasion rate and early lysosomal marker acquisition. These
      findings suggest that lysosomal exocytosis is important to EA cell invasion.
      Also, phagolysosome maturation in knockout cell lines differed from previous
      results revealing that EA enter cells by a mechanism other than receptor-mediated
      phagocytosis.

PMID- 19406100
TI  - Arginine 383 is a crucial residue in ABCG2 biogenesis.
AB  - ABCG2 is an ATP-binding cassette half-transporter initially identified in
      multidrug-resistant cancer cell lines and recently suggested to play an important
      role in pharmacokinetics. Here we report studies of a conserved arginine
      predicted to localize near the cytoplasmic side of TM1. First, we determined the
      effect of losing charge and bulk at this position via substitutions with glycine
      and alanine. The R383G mutant when transfected into HEK cells was not detectable
      on immunoblot or by functional assay, while the R383A mutant exhibited detectable
      but significantly decreased levels compared to wild-type, partial retention in
      the ER and altered glycosylation. Efflux of the ABCG2-substrates mitoxantrone and
      pheophorbide a was observed. Our experiments suggested rapid degradation of the
      R383A mutant by the proteasome via a kifunensine-insensitive pathway.
      Interestingly, overnight treatment of the R383A mutant with mitoxantrone assisted
      in protein maturation as evidenced by a shift to the N-glycosylated form. The
      R383A mutant when expressed in insect cells, though detected on the surface, had
      no measurable ATPase activity. In addition, substitution with the positively
      charged lysine resulted in significantly decreased protein expression levels in
      HEK cells, while retaining function. In conclusion, arginine 383 is a crucial
      residue for ABCG2 biogenesis, where even the most conservative mutations have a
      large impact.

PMID- 19406104
TI  - Avian reovirus influences phosphorylation of several factors involved in host
      protein translation including eukaryotic translation elongation factor 2 (eEF2)
      in Vero cells.
AB  - Viral infection usually influences cellular protein synthesis either actively or
      passively via modification of various translation initiation factors. Here we
      demonstrated that infection with avian reovirus (ARV) interfered with cellular
      protein synthesis. This study demonstrated for the first time that ARV influenced
      the phosphorylation of translation initiation factors including eIF4E and eIF-4G.
      Interestingly, ARV also induced phosphorylation of eukaryotic translation
      elongation factor (eEF2) in a time- and dose-dependent manner. Inhibition of mTOR
      by rapamycin notably increased the level of phosphorylated eEF2 in infected
      cells. However, rapamycin did not show any negative effects on ARV replication,
      suggesting that phosphorylation of eEF2 in infected cells did not reduce ARV
      propagation. These results demonstrated for the first time that ARV promotes
      phosphorylation of eEF2 which in turn influenced host protein production not
      simply by modulating the function of translation initiation factors but also by
      regulating elongation factor eEF2.

PMID- 19406105
TI  - Bestrophin genes are expressed in Xenopus development.
AB  - The Bestrophin-1/VMD2 gene has been implicated in Best disease, a juvenile-onset
      vitelliform macular dystrophy. The Bestrophin proteins have anion channel
      activity, and the four mammalian members share sequence homologies in multiple
      transmembrane domains and an RFP-tripeptide motif. The expression patterns and
      functions of the Bestrophin genes in retinal pigment epithelium have been studied
      intensively, whereas little is known about their roles in vertebrate
      embryogenesis. This study examined the roles of four Xenopus tropicalis homologs
      of BEST genes. The xtBest genes showed spatially and temporally distinct
      expression. xtBest-2 was the only maternally expressed Best gene, and both xtBest
      2 and the Xenopus laevis Best-2 gene were expressed at the edge of the blastopore
      lip including the organizer. Ectopic expression of xBest-2 caused defects in
      dorsal axis formation and in mesodermal gene expression during gastrulation.
      These results suggest a new role of the Bestrophin family genes in early
      vertebrate embryogenesis.

PMID- 19406106
TI  - Insulin-like growth factor-1 receptor activation prevents high glucose-induced
      mitochondrial dysfunction, cytochrome-c release and apoptosis.
AB  - Vascular disease is the leading cause of morbidity and mortality in patients with
      diabetes. Persistent hyperglycemia--the dominant metabolic derangement of
      diabetes, can cause endothelial cell apoptosis. Diabetes is often associated with
      low insulin like growth factor-1 (IGF-1), and the latter state has been linked to
      adverse risk profile and increased cardiovascular disease incidence. Since IGF-1
      acts as an important survival factor for multiple cell types, this study was to
      investigate whether IGF-1 exert regulatory effects on high glucose-induced
      apoptosis of vascular endothelial cells. Exposure to high glucose dose- and time
      dependently induced apoptotic changes (e.g., DNA fragmentation, altered
      mitochondrial membrane potential, and cytochrome-c release) in human umbilical
      vein endothelial cells (HUVECs). Addition of IGF-1 blocked the high glucose
      effect in a manner dependent on expression of IGF-1 receptor (IGF-1R) since
      silencing IGF-1R with small interference RNA could diminish the IGF-1' anti
      apoptosis effect. Our findings show that enhanced IGF-1 signaling inhibits
      glucose-induced apoptosis in HUVECs by reducing mitochondrial dysfunction, and
      maintaining the mitochondrial retention of cytochrome-c. These results may have
      therapeutic implications in preventing/reducing diabetes associated endothelial
      dysfunction.

PMID- 19406108
TI  - Evaluation of the binding orientations of testosterone in the active site of
      homology models for CYP2C11 and CYP2C13.
AB  - Cytochromes P-450 2C11 and 2C13 are the major CYPs in rat liver microsomes.
      Despite a high degree of sequence identity, these two isozymes display different
      positional and regio-specific metabolism of steroid hormones, such as
      testosterone. CYP2C11 converts testosterone to 2alpha-hydroxyl and 16alpha
      hydroxyl metabolites, while CYP2C13 produces primarily the 6beta-hydroxyl
      metabolite. Using a human CYP2C9 crystal structure as the template, homology
      models were generated for CYP2C11 and CYP2C13. Despite similar volume of the
      binding pockets for CYP2C11 and CYP2C13, the models for these two CYPs showed a
      substantial difference in the shape of the substrate-binding sites. Substrate
      docking using rigid and induced-fit methods showed that testosterone fits into
      the substrate-binding sites of both CYP2C11 and CYP2C13 without the need of added
      constraints. These docking exercises appear to support testosterone binding in
      both CYP2C11 and CYP2C13. A constrained docking using energy minimization is
      required to position testosterone for more precise positional and regio
      specificity in supporting the observed metabolism. These results demonstrate the
      complexity of using modeling for understanding the binding of substrate to CYPs,
      and suggest that, as a complement to the metabolism data, modeling and docking
      may yield reliable structural information for the molecular interaction between
      the substrate and the CYPs.

PMID- 19406110
TI  - Environmental housing affects the duration of mechanical allodynia and the spinal
      astroglial activation in a rat model of chronic inflammatory pain.
AB  - In this study, we aimed at investigating the effect of an enriched environment
      (EE) on the recovery from chronic inflammatory pain. Inflammatory pain was
      induced by the injection of 2 mg of carrageenan (CAR) into the right knee of male
      Sprague-Dawley rats (n=34). Rats were housed either singly (S-housed) or in an EE
      (EE-housed). The EE consisted of a large cage (L x W x H=2.0 x 1.0 x 0.8 m)
      containing various attributes (e.g. running wheels, shelter house, climbing
      frame). Withdrawal response to von Frey filament was used to assess mechanical
      allodynia at days post-operative (DPO) -1, 1, 7, 14, 21 and 28. S-housed animals
      showed a marked tactile sensitivity in the ipsilateral paw from DPO1 to DPO21.
      Four weeks after the CAR injection, S-housed rats were no longer allodynic. In
      contrast, EE-housed rats showed a significantly faster recovery: already at
      DPO21, they were no longer allodynic. In a first attempt to analyse the possible
      role of astroglial cells in the EE-induced effect, histological analysis at DPO21
      was performed. Immunohistochemical staining of the spinal dorsal horn at L3-L5
      indeed showed that spinal levels of astroglial activation are different between
      the two housing groups and therefore may play a role in the EE-induced effect on
      the duration of mechanical allodynia. In conclusion, our results showed that EE
      housing results in a reduced duration of mechanical allodynia in chronic
      inflammatory pain in rats. Astroglial activation is suggested to be involved in
      this housing effect.

PMID- 19406109
TI  - Neuroprotection of ethanol against cerebral ischemia/reperfusion induced brain
      injury through GABA receptor activation.
AB  - In this study we investigated whether ethanol could play neuroprotective effects
      against ischemic brain injury and the related mechanism. Cresyl violet staining
      results demonstrated that moderate dose of ethanol administered
      intracerebroventricularly (i.c.v.) had neuroprotective effect against ischemia
      reperfusion induced neuronal cell death. Ethanol also inhibited the
      phosphorylation of JNK3 induced by cerebral ischemia-reperfusion. Three separate
      drugs, NS3763 (the selective antagonist of GluR5), GluR5 antisense
      oligodeoxynucleotides (AS-ODNs) and Bicuculline (an antagonist of GABA
      receptors), were found to inhibit the neuroprotective effect of ethanol.
      Moreover, the GABA receptor agonist muscimol could attenuate the JNK3
      phosphorylation. Taken together, the results suggest that during ischemia
      reperfusion ethanol may activate presynaptic GluR5-KA and postsynaptic GABA
      receptors continuously, and the activation of GABA receptors inhibits the JNK3
      signal pathway. The results show a novel potential mechanism underlying ethanol
      protective effects.

PMID- 19406107
TI  - nAChR agonist-induced cognition enhancement: integration of cognitive and
      neuronal mechanisms.
AB  - The identification and characterization of drugs for the treatment of cognitive
      disorders has been hampered by the absence of comprehensive hypotheses. Such
      hypotheses consist of (a) a precisely defined cognitive operation that
      fundamentally underlies a range of cognitive abilities and capacities and, if
      impaired, contributes to the manifestation of diverse cognitive symptoms; (b)
      defined neuronal mechanisms proposed to mediate the cognitive operation of
      interest; (c) evidence indicating that the putative cognition enhancer
      facilitates these neuronal mechanisms; (d) and evidence indicating that the
      cognition enhancer facilitates cognitive performance by modulating these
      underlying neuronal mechanisms. The evidence on the neuronal and attentional
      effects of nAChR agonists, specifically agonists selective for alpha4beta2*
      nAChRs, has begun to support such a hypothesis. nAChR agonists facilitate the
      detection of signals by augmenting the transient increases in prefrontal
      cholinergic activity that are necessary for a signal to gain control over
      behavior in attentional contexts. The prefrontal microcircuitry mediating these
      effects include alpha4beta2* nAChRs situated on the terminals of thalamic inputs
      and the glutamatergic stimulation of cholinergic terminals via ionotropic
      glutamate receptors. Collectively, this evidence forms the basis for hypothesis
      guided development and characterization of cognition enhancers.

PMID- 19406111
TI  - Facilitation of motor imagery through movement-related cueing.
AB  - In the past few years, the use of motor imagery as an adjunct to other forms of
      training has been studied extensively. However, very little attention has been
      paid to how imagery could be used to greatest effect. It is well known that the
      provision of external cues has a beneficial effect on motor skill acquisition and
      performance during physical practice. Since physical execution and mental imagery
      share several common mechanisms, we hypothesized that motor imagery might be
      affected by external cues in a similar way. To examine this, we compared the
      motor imagery performance of three groups of 15 healthy participants who either
      physically performed or imagined performing a goal-directed cyclical wrist
      movement in the presence or the absence of visual and/or auditory external cues.
      As outcome measures, the participants' imagery vividness scores and eye movements
      were measured during all conditions. We found that visual movement-related cues
      improved the spatial accuracy of the participants' eye movements during imagery,
      while auditory cues specifically enhanced their temporal accuracy. Furthermore,
      both types of cues significantly improved the participants' imagery vividness.
      These findings indicate that subjects may imagine a movement in a better way when
      provided with external movement-related stimuli, which may possibly be useful
      with regard to the efficiency of mental practice in (clinical) training
      protocols.

PMID- 19406115
TI  - Determination of cell fates in the R7 equivalence group of the Drosophila eye by
      the concerted regulation of D-Pax2 and TTK88.
AB  - In the developing Drosophila eye, the precursors of the neuronal photoreceptor
      cells R1/R6/R7 and non-neuronal cone cells share the same developmental potential
      and constitute the R7 equivalence group. It is not clear how cells of this group
      elaborate their distinct fates. Here we show that both TTK88 and D-Pax2 play
      decisive roles in cone cell development and act in concert to transform
      developing R1/R6/R7 into cone cells: while TTK88 blocks neuronal development, D
      Pax2 promotes cone cell specification. In addition, ectopic TTK88 in R cells
      induces apoptosis, which is suppressed by ectopic D-Pax2. We further demonstrate
      that Phyllopod (Phyl), previously shown to promote the neuronal fate in R1/R6/R7
      by targeting TTK for degradation, also inhibits D-Pax2 transcription to prevent
      cone cell specification. Thus, the fates of R1/R6/R7 and cone cells are
      determined by a dual mechanism that coordinately activates one fate while
      inhibiting the other.

PMID- 19406112
TI  - Spinal NMDA NR1 subunit expression following transient TNBS colitis.
AB  - BACKGROUND: N-methyl-D-aspartic acid (NMDA) receptors play an important role in
      the development of hypersensitivity to visceral and somatic stimuli following
      inflammation or tissue injury. Our objective was to investigate the role of NMDA
      NR1 receptors in the spinal cord (T10-L1; L4-S1) of a subset of rats that remain
      hypersensitive following the histological resolution of TNBS-induced colitis
      compared to saline treated rats and rats that had recovered both behaviorally and
      histologically. We hypothesized that NMDA NR1 subunit expression mediates
      hypersensitivity following transient TNBS colitis. METHODS: Male Sprague-Dawley
      rats (150 g-250 g) received 20 mg/rat intracolonic trinitrobenzene sulfonic acid
      (TNBS) in 50% ethanol or saline. Animals underwent nociceptive visceral/somatic
      pain testing 16 weeks after resolution of TNBS colitis. Animals were sacrificed
      and their spinal cords (T10-L1; L4-S1) were retrieved and 2-dimensional
      polyacrylamide gel electrophoresis and immunohistocytochemistry techniques were
      used to investigate spinal-NMDA receptor expression. RESULTS: NR1(001) was the
      only NMDA NR1 receptor subunit that was expressed in recovered and control rats,
      whereas hypersensitive animals expressed NR1(011) and NR1(111) as well as
      NR1(001) subunits. Immunohistochemistry analysis demonstrated increased
      expression of NMDA NR1-N1, C1, and C2-plus expression in laminae I and II of the
      spinal cord (T10-L1; L4-S1) in hypersensitive rats but not in recovered/control
      rats. CONCLUSIONS: Selective increases in the expression of the NMDA NR1 splice
      variants occur in hypersensitive rats following resolution of TNBS colitis. This
      suggests that the NMDA NR1 receptor plays an important role in the development of
      neuronal plasticity and central sensitization. The recombination of NR1 splice
      variants may serve as a key functional protein that maintains hypersensitivity
      following resolution of TNBS colitis.

PMID- 19406114
TI  - SHB1 plays dual roles in photoperiodic and autonomous flowering.
AB  - Flowering was initiated by the integration of environmental signals such as day
      length with the internal development status in Arabidopsis, a facultative long
      day plant. The photoperiodic flowering involves two key components, CONSTANS and
      FT, whereas the autonomous flowering is operated through a central quantitative
      floral repressor, FLC, and several other genes that act upstream of FLC. SOC1
      acts downstream to integrate the flowering signals from the two pathways. Here,
      we report that SHB1 plays dual roles in both photoperiodic and autonomous
      flowering. shb1-D, a gain-of-function mutant, flowered early and shb1, a loss-of
      function allele, flowered late under both long days and short days. The shb1-D
      mutation activated the expression of CO, FT, and SOC1 under both long and short
      days, and however, the co-2 mutation attenuated the shb1-D activated expression
      of FT and SOC1 only under long days but not short days. The shb1-D or shb1
      mutations also reduced and increased, respectively, the expression of FLC under
      both long and short days. Transgenic remedy of FLC to wide-type level in shb1-D
      background also reverted shb1-D flowering and FT or SOC1 expression to wild type
      mostly under short days. Furthermore, the shb1-D suppression on FLC expression is
      likely operated through LD as ld-3 blocked this suppression and SHB1 appears to
      act upstream of LD. In summary, SHB1 represents signaling steps that regulate CO
      expression in leaves and LD or FLC expression in either leaves or shoot apical
      meristem, contributing to a threshold expression of SOC1 in shoot apical meristem
      for floral initiation.

PMID- 19406113
TI  - Transcriptional activities of the Pax6 gene eyeless regulate tissue specificity
      of ectopic eye formation in Drosophila.
AB  - Pax genes encode DNA binding proteins that play pivotal roles in the
      determination of complex tissues. Members of one subclass, Pax6, function as
      selector genes and play key roles in the retinal development of all seeing
      animals. Mutations within the Pax6 homologs including fly eyeless, mouse Small
      eye and human Pax6 lead to severe retinal defects in their respective systems. In
      Drosophila eyeless and twin of eyeless, play non-redundant roles in the
      developing retina. One particularly interesting characteristic of these genes is
      that, although expression of either gene can induce ectopic eye formation in non
      retinal tissues, there are differences in the location and frequencies at which
      the eyes develop. eyeless induces much larger ectopic eyes, at higher
      frequencies, and in a broader range of tissues than twin of eyeless. In this
      report we describe a series of experiments conducted in both yeast and flies that
      has identified protein modules that are responsible for the differences in tissue
      transformation. These domains appear to contain transcriptional activator and
      repressor activity of distinct strengths. We propose a model in which the
      selective presence of these activities and their relative strengths accounts, in
      part, for the disparity to which ectopic eyes are induced in response to the
      forced expression of eyeless and twin of eyeless. The identification of both
      transcriptional activator and repressor activity within the Pax6 protein furthers
      our understanding of how this gene family regulates tissue determination.

PMID- 19406117
TI  - Patterning of an ascidian embryo along the anterior-posterior axis through
      spatial regulation of competence and induction ability by maternally localized
      PEM.
AB  - In ascidian embryos, anterior-posterior (A-P) patterning of the vegetal cells is
      regulated by posteriorizing activities of a localized egg region known as
      posterior-vegetal cortex/cytoplasm (PVC). PEM is an essential component of the
      PVC and is involved in the posterior-specific cell cleavage pattern. Here we
      report a novel function of PEM independently of its function in cleavage
      regulation; it controls cell fate by excluding competence to respond to the FGF
      signal for notochord induction from posterior-vegetal cells. PEM was found to
      regulate the nuclear accumulation of beta-catenin, an upstream activator of the
      competence factor. PEM also influences A-P patterning in the animal hemisphere.
      It was found to regulate FGF signal expression and restrict the occurrence of
      brain induction only in the anterior region. Our results suggest a model in which
      PEM patterns the embryo along the A-P axis through regulation of the spatial
      distribution of competence and induction ability.

PMID- 19406116
TI  - Vasa and the germ line lineage in a colonial urochordate.
AB  - Germ cell sequestering in Animalia is enlightened by either, launching true germ
      line along epigenetic or preformistic modes of development, or by somatic
      embryogenesis, where no true germ line is set aside. The research on germ line
      somatic tissue segregation is of special relevancy to colonial organisms like
      botryllid ascidians that reconstruct, on a weekly basis, completely new sets of
      male and female gonads in newly formed somatic tissues. By sequencing and
      evaluating expression patterns of BS-Vasa, the Botryllus schlosseri orthologue of
      Vasa, in sexually mature and asexual colonies during blastogenesis, we have
      demonstrated that the BS-Vasa mRNA and protein are not expressed exclusively in
      germ cell lineages, but appeared in cells repeatedly emerging de novo in the
      colony, independently of its sexual state. In addition, we recorded an immediate
      Vasa response to cellular stress (UV irradiation) indicating additional functions
      to its germ line assignments. To confirm germ lineage exclusivity, we examined
      the expression of three more stem cell markers (BS-Pl10, Bl-piwi and Oct4). Vasa
      co-expression with Pl10 and Oct4 was detected in germ line derivatives and with
      Bl-piwi in somatic tissues. Presumptive primordial germ cells (PGC-like cells),
      that are Vasa(+)/Pl10(+)/Oct4(+) and 6-12 microm in diameter, were first detected
      in wrapped-tail embryos, in oozooids, in sexual/asexual colonies, within a newly
      identified PGC niche termed as 'budlet niche', and in circulating blood borne
      cells, indicating epigenetic embryogenesis. Alternatively, BS-Vasa co-expression
      with piwi orthologue, an omnipresent bona fide stemness flag, in non germ line
      cell populations, may indicate germ cell neogenesis (somatic embryogenesis) in B.
      schlosseri. Both alternatives are not necessarily mutually exclusive.

PMID- 19406118
TI  - Involvement of different types of potassium channels in the antidepressant-like
      effect of tramadol in the mouse forced swimming test.
AB  - Administration of tramadol elicited an antidepressant-like effect in the rat
      forced swimming test (FST) by a mechanism dependent on the inhibition of the L
      arginine-nitric oxide (NO)-guanylate cyclase pathway. Since it has been reported
      that NO can activate different types of potassium (K(+)) channels in several
      tissues, the present study investigated the possibility of synergistic
      interactions between different types of K(+) channel inhibitors and tramadol in
      the mouse FST. Intracerebroventricular pretreatment of mice with
      tetraethylammonium (TEA, a non-specific inhibitor of K(+) channels, 25 pg/site),
      glibenclamide (an ATP-sensitive K(+) channel inhibitor, 0.5 pg/site) or
      charybdotoxin (a large- and intermediate conductance calcium-activated K(+)
      channel inhibitor, 25 pg/site) was able to produce a synergistic action of a
      subeffective dose of tramadol (1 mg/kg, p.o.). Conversely, pretreatment with
      apamin (a small-conductance calcium-activated K(+) channel inhibitor, 10 pg/site)
      did not modify the action of a subeffective dose of tramadol (1 mg/kg, p.o.).
      Administration of tramadol and the K(+) channel inhibitors, alone or in
      combination, did not affect the number of crossings and rearings in the open
      field test (OFT). Reduction in the immobility time elicited by an active dose of
      tramadol (40 mg/kg, p.o.) in the FST was prevented by pretreatment of mice with
      cromakalim (a K(+) channel opener, 10 microg/site, i.c.v.), without affecting the
      number of crossings and rearings in the OFT. Thus, our findings clearly suggest
      that oral acute administration of tramadol produces antidepressant-like effect on
      the FST in mice by a mechanism that involves the K(+) channels.

PMID- 19406120
TI  - Establishment of medakafish as a model for stem cell-based gene therapy:
      efficient gene delivery and potential chromosomal integration by baculoviral
      vectors.
AB  - Viral vectors hold promise and challenges in gene therapy. Specifically, we have
      previously shown that baculoviral (BV) vectors have a high efficiency of gene
      delivery in human embryonic stem (ES) cells. Here we report the development of a
      complementary system to further our evaluation by utilizing the laboratory fish
      medaka that has ES cell lines and tools for experimental analyses in vitro and in
      vivo. We show that BV vectors can give rise to almost 100% of transient gene
      delivery in the medaka ES cell line MES1. BV-transduced MES1 cells reproducibly
      (at approximately 10(-5)) produce GFP-expressing colonies that, upon manual
      isolation, develop into stable clones during 300 days of culture. Surprisingly,
      BV transduction can also mediate efficient gene integration in the medaka genome,
      as fluorescent in situ hybridization revealed the presence of the BV-delivered
      gfp transgene in multiple locations in nuclei and on various chromosomes of
      metaphase spreads. We show that BV transduction does not compromise the genome
      stability and pluripotency of MES1 cells. We conclude that BV can efficiently
      mediate gene delivery and chromosomal integration in medaka ES cells. Therefore,
      medaka provides a powerful system for analyzing the potential of BV-mediated gene
      delivery in stem cells and gene therapy.

PMID- 19406119
TI  - Does telmisartan prevent hepatic fibrosis in rats with alloxan-induced diabetes?
AB  - BACKGROUND/AIMS: This study evaluated the effect of telmisartan on the livers of
      diabetic rats and also aimed to determine the hepatic distribution and role of
      transforming growth factor beta (TGF-beta) in diabetes-related hepatic
      degeneration while taking into account the possible protective effects of
      telmisartan. METHODS: Fifteen adult male rats were used and divided into three
      groups: the non-diabetic healthy group, alloxan-induced diabetic control group,
      and the alloxan-induced diabetic telmisartan group. The non-diabetic healthy
      group and the diabetic control group were exposed to saline for 30 days, while
      the group treated with diabetic drugs was orally administered telmisartan for 30
      days (10 mg/kg/day). At the end of the experiment, the rats were sacrificed and
      the livers were dissected and transferred into the fixation solution. The livers
      were then evaluated using stereological and histopathological methods. RESULTS:
      Our study of the numerical density of hepatocytes shows a significant difference
      between the diabetic control group and diabetic rats treated with telmisartan.
      Immunohistochemical staining for TGF-beta in liver sections of the diabetic rats
      treated with telmisartan showed no immunoreactivity. The diabetic control group
      was determined to be strongly immunoreactive to TGF-beta. CONCLUSION: Results
      suggest that telmisartan may reduce type-I diabetes mellitus-induced hepatic
      injury by suppressing activated hepatic stellate cells through concomitant TGF
      beta1 down-regulation.

PMID- 19406121
TI  - Akirin1 (Mighty), a novel promyogenic factor regulates muscle regeneration and
      cell chemotaxis.
AB  - Akirin1 (Mighty) is a downstream target gene of myostatin and has been shown to
      be a promyogenic factor. Although expressed in many tissues, akirin1 is
      negatively regulated by myostatin specifically in skeletal muscle tissue. In this
      manuscript we have characterized the possible function of akirin1 in postnatal
      muscle growth. Molecular and immunohistological analyses indicated that while low
      levels of akirin1 are associated with quiescent satellite cells (SC), higher
      levels of akirin1 are detected in activated proliferating SC indicating that
      akirin1 could be associated with satellite cell activation. In addition to SC,
      macrophages also express akirin1, and increased expression of akirin1 resulted in
      more efficient chemotaxis of both macrophages and myoblasts. Akirin1 appears to
      regulate chemotaxis of both macrophages and myoblasts by reorganising actin
      cytoskeleton, leading to more efficient lamellipodia formation via a PI3 kinase
      dependent pathway. Expression analysis during muscle regeneration also indicated
      that akirin1 expression is detected very early (day 2) in regenerating muscle,
      and expression gradually peaks to coincide the nascent myotube formation stage of
      muscle regeneration. Based on these results we propose that akirin1 could be
      acting as a transducer of early signals of muscle regeneration. Thus, we
      speculate that myostatin regulates key steps of muscle regeneration including
      chemotaxis of inflammatory cells, SC activation and migration through akirin1.

PMID- 19406123
TI  - Featuring... Frank Sargent winner of the 2009 FEBS Letters Young Scientist Award.
      Interview by Daniela Ruffell.

PMID- 19406122
TI  - Fem1a is a mitochondrial protein up-regulated upon ischemia-reperfusion injury.
AB  - Various expression studies have shown a preferential muscle expression of the
      mouse Fem1a gene, but no data is available on the subcellular localization of the
      corresponding protein. Here, using a specific antibody, we show that Fem1a is
      expressed preferentially in cardiac muscle, brain and liver. Moreover, using
      immunofluorescence and electron microscopy, as well as biochemical assays, we
      demonstrate that Fem1a is localized within mitochondria of C2C12 myoblasts and
      cardiac muscle cells. Finally, we show that the expression of Fem1a, which is a
      cellular partner of the EP4 receptor for prostaglandin E(2), is increased in
      mouse hearts after myocardial infarction.

PMID- 19406124
TI  - Hippocampal and striatal dependent navigation: sex differences are limited to
      acquisition.
AB  - Estrogen has been demonstrated to enhance the use of hippocampal-based place
      learning while reducing the use of striatal-based motor-response strategy (Korol,
      D.L., Malin, E.L., Borden, K.A., Busby, R.A., & Couper-Leo, J. (2004). Shifts in
      preferred learning strategy across the estrous cycle in female rats. Horm. Behav.
      45, 330-338). Previous research has focused on task acquisition and the switch
      from a place to motor-response navigation with training. The current paradigm
      allowed an examination of the interplay between these two systems by having well
      trained animals switch strategies "on demand." Female and male Sprague-Dawley
      rats were taught a motor-response task on a plus maze. The rats were then
      introduced to a place task and taught to switch, by cue, from the motor-response
      to place strategy. Finally, the rats were trained to continuously alternate
      between place and motor-responses strategies. The maze configuration allowed for
      an analysis of cooperative choices (both strategies result in the same goal arm),
      competitive choices (both strategies result in different goal arms), and single
      strategy choices (can only use the motor-response strategy). The results indicate
      that sex and estrogen-related effects on navigation strategy are limited to the
      initial stages of learning a task. The role of sex and estrogen is diminished
      once the task is well learned, and presumably, the relative involvement of the
      hippocampal and striatal systems is established.

PMID- 19406125
TI  - Preconditioning with diazoxide prevents reoxygenation-induced rigor-type
      hypercontracture.
AB  - Ischemic preconditioning has a powerful protective potential against a
      reperfusion-induced injury of the post-ischemic myocardium. Cardiomyocyte
      hypercontracture, i.e. excessive cell shortening, is an essential mechanism of
      the reperfusion-induced injury. Rigor contracture, i.e. Ca(2+)-independent
      contracture, has been shown to be an import component of the reperfusion-induced
      hypercontracture. Since rigor contracture is dependent on the rapidity of the
      metabolic recovery during reoxygenation, we hypothesized that preconditioning of
      the cardiomyocyte mitochondria may improve mitochondrial function to restore the
      energy balance during the initial phase of reoxygenation and may thus prevent
      rigor contracture. For this purpose adult rat cardiomyocytes were exposed to
      anoxia with subsequent reoxygenation. For preconditioning, cells were pre-treated
      with the mitochondrial ATP-sensitive K(+) channel opener diazoxide. Pre-treatment
      with 100 micromol/l diazoxide significantly reduced the reoxygenation-induced
      hypercontracture of cardiomyocytes due to an attenuation of the Ca(2+)
      independent rigor-type contracture, which was accompanied by an acceleration of
      the phosphocreatine resynthesis during the initial phase of reoxygenation.
      Treatment with the mitochondrial ATP-sensitive K(+) channel antagonist 5
      hydroxydecanoate (500 micromol/l) during preconditioning phase abolished these
      protective effects. Similarly, partial suppression of the mitochondrial function
      with 100 micromol/l NaCN during the reoxygenation phase abolished the diazoxide
      effects. Finally, in isolated rat hearts, preconditioning with diazoxide prior to
      global ischemia significantly improved left ventricular function and attenuated
      hypercontracture during reperfusion. This effect could be abolished by the
      treatment with 100 micromol/l NaCN during reperfusion. Taken together,
      pharmacological preconditioning of cardiomyocytes with diazoxide protects against
      the reoxygenation-induced rigor hypercontracture due to an improvement of the
      energy recovery at the onset of reoxygenation.

PMID- 19406126
TI  - Stress-induced dilated cardiomyopathy in a knock-in mouse model mimicking human
      titin-based disease.
AB  - Mutations in a variety of myofibrillar genes cause dilated cardiomyopathy (DCM)
      in humans, usually with dominant inheritance and incomplete penetrance. Here, we
      sought to clarify the functional effects of the previously identified DCM-causing
      TTN 2-bp insertion mutation (c.43628insAT) and generated a titin knock-in mouse
      model mimicking the c.43628insAT allele. Mutant embryos homozygous for the Ttn
      knock-in mutation developed defects in sarcomere formation and consequently died
      before E9.5. Heterozygous mice were viable and demonstrated normal cardiac
      morphology, function and muscle mechanics. mRNA and protein expression studies on
      heterozygous hearts demonstrated elevated wild-type titin mRNA under resting
      conditions, suggesting that up-regulation of the wild-type titin allele
      compensates for the unstable mutated titin under these conditions. When
      chronically exposed to angiotensin II or isoproterenol, heterozygous mice
      developed marked left ventricular dilatation (p<0.05) with impaired fractional
      shortening (p<0.001) and diffuse myocardial fibrosis (11.95+/-2.8% vs. 3.7+/
      1.1%). Thus, this model mimics typical features of human dilated cardiomyopathy
      and may further our understanding of how titin mutations perturb cardiac function
      and remodel the heart.

PMID- 19406127
TI  - Contributions of interfacial residues of human Interleukin15 to the specificity
      and affinity for its private alpha-receptor.
AB  - Human interleukin 15 (hIL15) is a soluble cytokine that plays a key role in the
      maintenance of long-lasting responses against pathogens and a valuable target for
      the treatment of autoimmune diseases. In this study, we sought to elucidate the
      thermodynamic basis of the recognition mechanism for its private alpha-receptor
      (hIL15Ralpha), considered the first step of the interleukin's activation pathway.
      Binding of wild-type hIL15 to its alpha-receptor is characterized by a very slow
      dissociation rate constant and driven by a favorable enthalpy change. We further
      studied the kinetic and energetic consequences of substituting residues of hIL15
      located at the contact interface by means of the surface plasmon resonance
      technique. Replacement of negatively charged residues with Ala indicates that the
      energetics of interaction is primarily driven by electrostatic forces, manifested
      by a dramatic acceleration of the dissociation step and a reduction of favorable
      binding enthalpy. Our analyses also unveiled a novel and critical role for
      residue Tyr26 in the interaction, which facilitates desolvation of key charged
      residues during the assembly of the complex. These results were rationalized in
      terms of a previously reported structure of hIL15.hIL15alpha, demonstrating that
      the binding energetics is dominated by interactions occurring at three hot spots
      whose spatial locations coincide with a previously proposed structural division
      of the contact interface in three regions. Specifically, Region 1 is the main
      contributor to the binding energy of the complex by establishing very favorable
      electrostatic interactions with the receptor; Region 2 is also dominated by
      electrostatic forces, although of a lesser intensity; and Region 3 confers
      specificity to the association by means of high shape complementarity and by
      bringing additional stabilization energy to the complex. The biological impact of
      hIL15 mutations with the most effect on alpha-receptor binding was evaluated in a
      cell-based proliferation assay, validating the conclusions of our thermodynamic
      analyses and highlighting the functional importance of molecular contacts that
      promote prolonged binding of the interleukin to the alpha-receptor. In closing,
      the thermodynamics and physicochemical nature of the interactions observed in
      IL15h.IL15Ralpha complex, together with interactions in Region 3 of the
      interleukin, poses a stark contrast with the structurally related and sometimes
      functionally redundant interleukin 2.

PMID- 19406128
TI  - Mechanism of aquaporin-4's fast and highly selective water conduction and proton
      exclusion.
AB  - Members of the aquaporin (AQP) family are expressed in almost every organism,
      including 13 homologues in humans. Based on the electron crystallographic
      structure of AQP1, the hydrogen-bond isolation mechanism was proposed to explain
      why AQPs are impermeable to protons despite their very fast water conduction. The
      mechanism by which AQPs exclude protons remained controversial, however. Here we
      present the structure of AQP4 at 2.8 A resolution obtained by electron
      crystallography of double-layered two-dimensional crystals. The resolution has
      been improved from the previous 3.2 A, with accompanying improvement in data
      quality resulting in the ability to identify individual water molecules. Our
      structure of AQP4, the predominant water channel in the brain, reveals eight
      water molecules in the channel. The arrangement of the waters provides support
      for the hydrogen-bond isolation mechanism. Our AQP4 structure also visualizes
      five lipids, showing that direct interactions of the extracellular surface of
      AQP4 with three lipids in the adjoining membrane help stabilize the membrane
      junction.

PMID- 19406129
TI  - The role of large environmental noise in masting: general model and example from
      pistachio trees.
AB  - Masting is synchronous, highly variable reproduction in a plant population, or
      synchronized boom-bust cycles of reproduction. These pulses of resources have
      cascading effects through ecosystems, and thus it is important to understand
      where they come from. How does masting happen and synchronize? In this paper, we
      suggest a mechanism for this. The mechanism is inspired by data from a pistachio
      orchard, which suggest that large environmental noise may play a crucial role in
      inducing masting in plant populations such as pistachio. We test this idea
      through development and analysis of a mathematical model of plant reproduction.
      We start with a very simple model, and generalize it based on the current models
      of plant reproduction and masting. Our results suggest that large environmental
      noise may indeed be a crucial part of the mechanism of masting in certain types
      of plant populations, including pistachio. This is a specific example of an
      important functional consequence of the interactions between stochasticity and
      nonlinearity.

PMID- 19406130
TI  - A task-specific validation of homogeneous non-linear optimisation approaches.
AB  - In biomechanics, musculoskeletal models are typically redundant. This situation
      is referred to as the distribution problem. Often, static, non-linear
      optimisation methods of the form "min: phi(f) subject to mechanical and muscular
      constraints" have been used to extract a unique set of muscle forces. Here, we
      present a method for validating this class of non-linear optimisation approaches
      where the homogeneous cost function, phi(f), is used to solve the distribution
      problem. We show that the predicted muscle forces for different loading
      conditions are scaled versions of each other if the joint loading conditions are
      just scaled versions. Therefore, we can calculate the theoretical muscle forces
      for different experimental conditions based on the measured muscle forces and
      joint loadings taken from one experimental condition and assuming that all input
      into the optimisation (e.g., moment arms, muscle attachment sites, size, fibre
      type distribution) and the optimisation approach are perfectly correct. Thus
      predictions of muscle force for other experimental conditions are accurate if the
      optimisation approach is appropriate, independent of the musculoskeletal geometry
      and other input required for the optimisation procedure. By comparing the muscle
      forces predicted in this way to the actual muscle forces obtained experimentally,
      we conclude that convex homogeneous non-linear optimisation approaches cannot
      predict individual muscle forces properly, as force-sharing among synergistic
      muscles obtained experimentally are not just scaled versions of joint loading,
      not even in a first approximation.

PMID- 19406131
TI  - Multiclass cancer classification by support vector machines with class-wise
      optimized genes and probability estimates.
AB  - We investigate the multiclass classification of cancer microarray samples. In
      contrast to classification of two cancer types from gene expression data,
      multiclass classification of more than two cancer types are relatively hard and
      less studied problem. We used class-wise optimized genes with corresponding one
      versus-all support vector machine (OVA-SVM) classifier to maximize the
      utilization of selected genes. Final prediction was made by using probability
      scores from all classifiers. We used three different methods of estimating
      probability from decision value. Among the three probability methods, Platt's
      approach was more consistent, whereas, isotonic approach performed better for
      datasets with unequal proportion of samples in different classes. Probability
      based decision does not only gives true and fair comparison between different one
      versus-all (OVA) classifiers but also gives the possibility of using them for any
      post analysis. Several ensemble experiments, an example of post analysis, of the
      three probability methods were implemented to study their effect in improving the
      classification accuracy. We observe that ensemble did help in improving the
      predictive accuracy of cancer data sets especially involving unbalanced samples.
      Four-fold external stratified cross-validation experiment was performed on the
      six multiclass cancer datasets to obtain unbiased estimates of prediction
      accuracies. Analysis of class-wise frequently selected genes on two cancer
      datasets demonstrated that the approach was able to select important and relevant
      genes consistent to literature. This study demonstrates successful implementation
      of the framework of class-wise feature selection and multiclass classification
      for prediction of cancer subtypes on six datasets.

PMID- 19406132
TI  - Computed tomographic colonography and high-risk adenomas: a gap in the
      guidelines?

PMID- 19406134
TI  - Allele-specific expression as a new genetic susceptibility mechanism for
      colorectal cancer.

PMID- 19406133
TI  - Evidence for the role of the brain-gut axis in inflammatory bowel disease:
      depression as cause and effect?

PMID- 19406135
TI  - Myth and reality underlying the needed expansion of graduate medical education.

PMID- 19406136
TI  - Radiofrequency ablation of Barrett's esophagus: should everybody get it?

PMID- 19406137
TI  - Upper gastrointestinal involvement in pediatric Crohn's disease.

PMID- 19406141
TI  - A perspective on bi-allelic MUTYH mutations in patients with hyperplastic
      polyposis syndrome.

PMID- 19406142
TI  - Polymorphism in cytochrome P450 2A6 and glutathione S-transferase P1 modifies
      head and neck cancer risk and treatment outcome.
AB  - A case control study was carried out to investigate the association of
      functionally important polymorphism in cytochrome P450 2A6 (CYP2A6) and
      glutathione S-transferase P1 (GSTP1) genes with head and neck squamous cell
      carcinoma (HNSCC) and treatment response in cases receiving a combination of
      chemo-radiotherapy. The study group consisted of 350 males suffering from HNSCC
      and an equal number of male controls. Multivariate logistic regression analysis
      revealed statistically significant decrease in risk to HNSCC in cases with
      variant genotypes (CYP2A6*1B and CYP2A6*4C) of CYP2A6 (OR: 0.78; 95% CI: 0.43
      1.22; P=0.04) or GSTP1 (OR: 0.71; 95% CI: 0.51-1.00; P=0.05). The risk associated
      with these variant genotypes was found to be further decreased in cases carrying
      a combination of variant genotypes of CYP2A6 and GSTP1 (OR: 0.40; 95% CI: 0.25
      0.65; P=0.00). A similar decrease in risk was observed in cases with variant
      genotypes of CYP2A6 (OR: 0.59; 95% CI: 0.40-0.86; P=0.00) or GSTP1 (OR: 0.62; 95%
      CI: 0.42-0.91; P=0.01) and who were regular tobacco users (cigarette smokers or
      tobacco chewers). Interestingly, only 27% of the cases carrying the variant forms
      of CYP2A6 (*1A/*4C+*1B/*4C+*4C/*4C) responded to the treatment for HNSCC when
      compared to those with wild-type genotype (69%). However with GSTP1, cases with
      homozygous mutant genotype (Val/Val) showed a superior treatment response (75%)
      when compared to cases with wild-type genotype (25%). Further, cases carrying a
      combination of variant genotype of CYP2A6 and wild-type genotype of GSTP1
      exhibited a very poor treatment response demonstrating that polymorphisms in
      CYP2A6 and GSTP1 not only modified the risk to HNSCC but also played a major role
      in determining the chemotherapeutic response.

PMID- 19406143
TI  - Approachability and the amygdala: insights from Williams syndrome.
AB  - Williams syndrome (WS) is a genetic neurodevelopmental disorder in which
      hypersociability is a characteristic feature. Given that the amygdala has been
      identified as an integral component of the neural system underlying sociability,
      researchers have suggested that the abnormal amygdala volumes found in
      individuals with WS may play a role in their hypersociability. The aim of this
      study was to examine the relationship between amygdala volume and
      hypersociability, as measured by approachability ratings, in 22 individuals with
      WS and 22 normal controls matched on chronological age, sex, and handedness. We
      confirmed previous findings of increased amygdala volumes and higher
      approachability ratings of both 'positive' and 'negative' faces in individuals
      with WS. A positive relationship between right amygdala volume and
      approachability ratings was found in individuals with WS, particularly ratings of
      'negative' faces. The results unexpectedly revealed that individuals with WS
      report using features other than the eyes and mouth to determine approachability,
      particularly when they are younger. These findings support the theory that
      amygdala dysfunction in WS is related to their hypersociability. Furthermore, we
      propose that individuals with WS use atypical cognitive strategies compared to
      controls to determine approachability.

PMID- 19406144
TI  - Novel C-6 substituted and unsubstituted pregnane derivatives as 5alpha-reductase
      inhibitors and their effect on hamster flank organs diameter size.
AB  - The present study is addressed to ascertain the inhibitory effect of several
      progesterone derivatives having a chlorine substituent at C-6 (12a-12d), 15 with
      a bromine substituent at C-6 and 14a-14d, without any halogen atom at C-6 all
      having an ester side chain at C-17 (benzoate ester bearing a Cl, F and a Br atom
      at C-4 position of the phenyl ring) on the 5alpha-reductase enzyme activity
      present in human prostate. In addition, it was also of interest to investigate
      the pharmacological effect on hamster flank organs diameter size. In order to
      study the structure-activity relationships of steroids 12a-12d, 14a-14d and 15 we
      determined the concentration of these steroids that inhibited 50% of the activity
      of human prostate 5alpha-reductase enzyme (IC(50)), as well as the in vivo effect
      of these compounds in the hamster flank organs diameter size. We also
      ascertained, the capacity of these steroids to bind to the androgen receptors
      present in the rat prostate cytosol using labeled mibolerone (MIB) for monitoring
      the binding to the androgen receptor. The results from this study indicated that
      compounds 12a-12d (having a chlorine substituent at C-6), 14a-14d (lacking a
      halogen atom at C-6), 13 and 15 (having a bromine atom at C-6) showed an
      increased antiandrogenic effect (lower value for the diameter of the flank
      organs) as compared to the flank organs from testosterone-treated hamsters. On
      the other hand, the series of compounds containing a chlorine substituent at C-6
      compounds (12a-12d) showed a higher antiandrogenic activity as compared to the
      compounds lacking a halogen atom at C-6 (14a, 14b and 14d). Although compounds 13
      and 15 decreased the flank organs diameter size, however, this increase was not
      statistically significant as compared to that of the commercially available
      product finasteride. The steroidal derivatives 13, 14a-14d (lacking the chlorine
      substituent at C-6) and 15 (having a bromine atom at C-6) exhibited a higher
      5alpha-reductase inhibitory activity (lower IC(50) values) as compared to the
      series of compounds 12a-12d having the halogen substituent at C-6. Finasteride
      reduced the diameter size of the flank organs. The effect of this steroid and
      compounds 12a-12d, 13, 14a-14d and 15 on hamster flank organs can be explained by
      the fact that these steroids did not bind to the androgens receptor, which
      indicates that its mechanism of action is an inhibiting for the 5alpha-reductase
      activity. This enzyme is present in the hamster flank organs and was inhibited by
      the novel steroids in the human prostate homogenates.

PMID- 19406146
TI  - The effect of eating behavior on weight loss and maintenance during a lifestyle
      intervention.
AB  - OBJECTIVE: To investigate the effects of intensive counseling on eating behavior
      and weight loss and maintenance and their associations. METHODS: A randomized
      weight loss counseling intervention with follow-up of 18 months, conducted
      between 2002-2004 at Oulu University Hospital, Finland included obese adults
      (n=82, body mass index >27 kg/m(2)). Subjects were randomized into 1) intensive
      counseling and 2) short-term counseling. Forty-nine subjects who completed the
      study were included. Eating behavior was repeatedly assessed by the Three Factor
      Eating Questionnaire-18 and Binge Eating Scale. RESULTS: Eating behavior improved
      in both groups. Effect of counseling was -5.0+/-5.7 kg compared with -2.4+/-2.5
      kg in the control group (p<0.05 between the groups) during the first 6 months. At
      18 months the weight loss results were -2.6+/-6 kg and -0.7+/-3.5 kg,
      respectively (NS). Success in weight loss maintenance is associated with improved
      eating behavior (p<0.05). By contrast, failure in weight loss is associated with
      high scores of uncontrolled eating and binge eating symptoms at the baseline
      (p<0.05). CONCLUSIONS: Both intensive and short-term interventions improved
      eating behavior and weight loss but there was no difference between the two modes
      of intervention. The association between the improvement of eating behaviour and
      the success of weight loss suggests a causal relationship which however should be
      confirmed in a prospective study focusing specifically on this aspect.

PMID- 19406147
TI  - Validity and prognostic value of parental ratings of children's activity.
AB  - OBJECTIVE: To determine whether parental reports of children's physical activity
      are stable over time and correlate with objectively-measured physical activity.
      METHODS: Participants were 322 twin children from a large UK twin cohort. When
      the children were aged 4 (1999) and 11 (2006), mothers rated their activity
      levels using four different measures. These included children's enjoyment of
      active pastimes, their habitual activity level, their activity compared with
      others of the same age and sex and a standard scale for 'fidgetiness'. Children
      wore an Actigraph (model 7164) for 7 consecutive days at the 11 year follow up
      from which total physical activity was calculated. RESULTS: From age 4 to 11
      amount and enjoyment of physical activity declined, but significant temporal
      correlations over the 7 year interval (range r=0.19 to 0.52) suggested that
      relative activity level was maintained. Habitual physical activity level,
      enjoyment of activity and fidgetiness at age 11 were all significantly associated
      with activity counts (all p values<0.05). CONCLUSIONS: These results indicate
      that parental ratings can be valid indicators of children's physical activity,
      and that children who are perceived to be more active at 4 years are still more
      active at 11 years.

PMID- 19406148
TI  - On sex/gender related similarities and differences in fMRI language research.
AB  - Again and again, attempts have been made to find correlates of sex/gender
      differences in the human brain. Despite the insistence with which differences
      have been stated, empirical results have not been unequivocal: evidence for and
      against the influence of sex in the makeup of men's and women's brains has been
      presented. This article focuses on the relevance of sex/gender related
      differences in fMRI research, especially with regard to language processing. By
      discussing some crucial criteria from fMRI examinations, we demonstrate the
      existence of paradigmatic, methodological and statistical defaults that interfere
      with assessing the presence or absence of sex/gender differences. These criteria
      are, among others, the use of contrast analyses, the function of the variable
      sex/gender as a co-item and the "publication bias". It is argued that dealing
      with the sex/gender variable will, at least to some degree, inevitably lead to
      the detection of differences rather than to the detection of similarities.

PMID- 19406145
TI  - Chronic NF-kappaB activation delays RasV12-induced premature senescence of human
      fibroblasts by suppressing the DNA damage checkpoint response.
AB  - Normal cells divide for a limited number of generations, after which they enter a
      state of irreversible growth arrest termed replicative senescence. While
      replicative senescence is due to telomere erosion, normal human fibroblasts can
      undergo stress-induced senescence in response to oncogene activation, termed
      oncogene-induced senescence (OIS). Both, replicative and OIS, initiate a DNA
      damage checkpoint response (DDR) resulting in the activation of the p53
      p21(Cip1/Waf1) pathway. However, while the nuclear factor-kappaB (NF-kappaB)
      signaling pathway has been implicated in DDR, its role in OIS has not been
      investigated. Here, we show that oncogenic Ha-RasV12 promoted premature
      senescence of IMR-90 normal human diploid fibroblasts by activating DDR, hence
      verifying the classical model of OIS. However, enforced expression of a
      constitutively active IKKbeta T-loop mutant protein (IKKbetaca), significantly
      delayed OIS of IMR-90 cells by suppressing Ha-RasV12 instigated DDR. Thus, our
      experiments have uncovered an important selective advantage in chronically
      activating canonical NF-kappaB signaling to overcome the anti-proliferative OIS
      response of normal primary human fibroblasts.

PMID- 19406149
TI  - Event-related oscillations in mice: effects of stimulus characteristics.
AB  - Event-related oscillations (EROs) are rhythmic changes that are evoked by sensory
      and/or cognitive processes that influence the dynamics of the EEG. EROs are
      estimated by a decomposition of the EEG signal into phase and magnitude
      information for a range of frequencies and then changes in those frequencies are
      characterized over a millisecond time scale with respect to task events. EROs
      have been demonstrated to be sensitive measures of both normal and abnormal
      cognitive functioning in humans but have not been fully described in mice. The
      results of these studies demonstrate that EROs can be generated in cortical sites
      in mice in the delta, theta, alpha/beta frequency ranges in response to auditory
      stimuli. Oscillations in the 7.5-40 Hz frequencies were significantly affected in
      the 0-50 ms time range in response to differences in tone frequency. Whereas,
      changes in tone loudness produced changes in oscillations in the 7.5-40 Hz
      frequencies in the 350-800 ms range. No significant changes in EROs were found to
      differences in tone probability. These studies suggest that EROs are an
      electrophysiological assay sensitive to tone characteristics and as such may be
      suitable for the exploration of the effects of genetic or neuropharmacological
      manipulations on neurosensory processing in mice.

PMID- 19406151
TI  - Effect of cancellation on triggered averaging used to determine synchronization
      between motor unit discharge in separate muscles.
AB  - Synchronization between single motor unit (SMU) discharges in separate muscles
      has been estimated from peaks in averaged electromyographic (EMG) recordings from
      one muscle triggered from SMU discharge in another. This study evaluated the
      effect of EMG signal cancellation on this measure of synchronization. SMU
      activity was recorded with 8 fine-wire electrodes in vastus medialis obliquus
      (VMO) and vastus lateralis (VL) during gentle isometric knee extension in 7
      subjects. Data from 5 VL recordings were summed then rectified, or rectified then
      summed, to produce multi-unit recordings with and without cancellation,
      respectively. Averages of summed VL data were triggered from VMO SMUs.
      Synchronization, defined as a peak >3 SD above the triggered average mean,
      occurred in 73.68% and 78.95% of recordings with and without cancellation,
      respectively. To further investigate the effect of cancellation on
      synchronization, 250 "virtual" EMG recordings were created from VL data. VL SMUs
      were sorted and modified with respect to discharge rate, amplitude and polarity
      to create a collection of possible SMU discharge patterns. Virtual recordings
      were added one-by-one to VL recordings that showed synchronization. Virtual
      channels were rectified then added or added then rectified, to create data with
      and without cancellation. Identification of synchronization decreased similarly
      in both conditions with addition of virtual data. Our data show estimation of
      synchronization from triggered averages is more likely to detect synchronization
      in recordings with fewer SMUs, but cancellation has little effect.
      Synchronization must be interpreted with caution if number of SMUs changes
      between conditions.

PMID- 19406150
TI  - The optimization of TaqMan real-time RT-PCR assay for transcriptional profiling
      of GABA-A receptor subunit plasticity.
AB  - The GABA-A receptor plays a critical role in inhibitory neurotransmission in the
      brain. Quantitation of GABA-A receptor subunits in various brain regions is
      essential to understand their role in plasticity and brain disorders. However,
      conventional RNA assays are tedious and less sensitive for use in studies of
      subunit plasticity. Here we describe optimization of a sensitive assay of GABA-A
      receptor subunit gene expression by TaqMan real-time PCR. For each subunit gene,
      a set of primers and TaqMan fluorogenic probe were designed to specifically
      amplify the target template. The TaqMan methodology was optimized for
      quantification of mouse GABA-A receptor subunits (alpha(1-6), beta(1-3),
      gamma(2), and delta) and GAPDH. The TaqMan reaction detected very low levels of
      gene expression ( approximately 100 template copies of cDNA). A standard curve
      for GAPDH and one of the target genes, constructed using the cDNA, revealed
      slopes around -3.4 (r(2)=0.990), reflecting similar optimum PCR efficiencies. The
      methodology was utilized for quantification of the GABA-A receptor alpha(4)
      subunit, which is known to upregulate following withdrawal from chronic
      progesterone or neurosteroids. Our results show that the alpha(4)-subunit
      expression increased threefold in the hippocampus following neurosteroid
      withdrawal in mice. The TaqMan PCR assay allows sensitive, high-throughput
      transcriptional profiling of complete GABA-A receptor subunit family, and thus
      provides specific tool for studies of GABA-A receptor subunit plasticity in
      neurological and psychiatric animal models.

PMID- 19406152
TI  - Analysis of sialoadhesin expression on mouse alveolar macrophages.
AB  - Sialoadhesin (Sn) is a macrophage-restricted receptor that was first
      characterised on mouse resident bone marrow macrophages as a receptor that
      mediates the binding, without ingestion, of sheep erythrocytes. Sn is highly
      conserved in mammals but its expression on tissue macrophages is heterogeneous.
      In the mouse, high levels of erythrocytes binding are shown on macrophages from
      lymphoid tissues but a low erythrocytes binding activity is detectable on
      macrophages isolated from the broncho-alveolar space. Yet, Sn expression has been
      demonstrated on human, rat and pig alveolar macrophages (AM) using methods of
      molecular biology. Therefore, the present study aimed to investigate the
      expression of Sn on mouse AM in order to confirm the presence of the protein on
      this population of murine macrophages. Using cytometrical analyses, we showed
      that Sn was expressed on mouse AM surface. Following desialylation, AM largely
      bound erythrocytes and this binding was inhibited by 3D6, an anti-mouse Sn
      monoclonal antibody, in a dose-dependent manner. This indicates that Sn is
      expressed on mouse AM but that the sialic acid binding activity mediated by this
      molecule is naturally masked by endogenous sialic acid within the glycocalyx on
      the cell surface.

PMID- 19406153
TI  - Unimpaired immune functions in the absence of Mrp4 (Abcc4).
AB  - Dendritic cell (DC) migration to draining lymph nodes is important for the
      initiation of an effective immune response. Recently we reported that the human
      ATP-binding cassette (ABC) transporter multidrug resistance protein 4 (MRP4 and
      ABCC4) is required for the migration of human DC. Since the ABC transporter MRP1
      (ABCC1) was previously shown to play a role in both human and mouse DC migration,
      we here studied whether Mrp4 is similarly required for DC migration in mice and
      whether the absence of Mrp4 interferes with the generation of an immune response.
      Immunological responses were compared in wild-type FVB (FVBwt), FVB Mrp4 knockout
      (KO) or FVB Mrp4/5 double knockout (dKO) mice. Skin, a preferred immunization
      site, was analyzed for DC markers, as well as for Mrp1 and Mrp4 expression.
      Whereas Mrp1 was abundantly present within FVBwt skin, only few Mrp4 expressing
      cells were detected. In addition, no Mrp4 protein expression was detected on in
      vitro cultured FVBwt bone marrow-derived DC (BM-DC). DC migration from murine ear
      skin was unaltered between FVBwt and MRP4/5 dKO animals. The absence of Mrp4 also
      had no effect on immune responses upon allergen sensitization, immunization or
      oral tolerance induction. We thus conclude that in contrast to its human
      counterpart, murine Mrp4 is not involved in DC migration, nor indeed, in the
      generation of an effective immune response. These data reveal disparities in the
      physiological role of ABC transporters between species, which may derive from
      differences in substrate specificity.

PMID- 19406154
TI  - A simple, rapid and inexpensive method for localization of Tomato yellow leaf
      curl virus and Potato leafroll virus in plant and insect vectors.
AB  - A simple, rapid, inexpensive method for the localization of virus transcripts in
      plant and insect vector tissues is reported here. The method based on fluorescent
      in situ hybridization using short DNA oligonucleotides complementary to an RNA
      segment representing a virus transcript in the infected plant or insect vector.
      The DNA probe harbors a fluorescent molecule at its 5' or 3' ends. The protocol:
      simple fixation, hybridization, minimal washing and confocal microscopy, provides
      a highly specific signal. The reliability of the protocol was tested by
      localizing two phloem-limited plant virus transcripts in infected plants and
      insect tissues: Tomato yellow leaf curl virus (TYLCV) (Begomovirus:
      Geminiviridae), exclusively transmitted by the whitefly Bemisia tabaci
      (Gennadius) in a circulative non-propagative manner, and Potato leafroll virus
      (Polerovirus: Luteoviridae), similarly transmitted by the aphid Myzus persicae
      (Sulzer). Transcripts for both viruses were localized specifically to the phloem
      sieve elements of infected plants, while negative controls showed no signal.
      TYLCV transcripts were also localized to the digestive tract of B. tabaci,
      confirming TYLCV route of transmission. Compared to previous methods for
      localizing virus transcripts in plant and insect tissues that include complex
      steps for in-vitro probe preparation or antibody raising, tissue fixation, block
      preparation, sectioning and hybridization, the method described below provides
      very reliable, convincing, background-free results with much less time, effort
      and cost.

PMID- 19406156
TI  - Evaluation of Epstein-Barr virus antibodies, anti-VCA avidity by
      immunofluorescence and immunoblot assays for assessment of Epstein-Barr virus
      immunologic state.
AB  - Three hundred twenty two serum samples were evaluated by indirect
      immunofluorescence assay (IFA) and immunoblotting for the assessment of the
      immunologic status of Epstein-Barr virus (EBV). Serological profiles of 322 serum
      samples were classified by the IgM and IgG antibodies by the immunofluorescence
      assay as seronegative, acute infection, reactivation and past infection. Higher
      rates of seropositivity were determined in serum samples belonging to old age
      groups. Routine tests used for EBV diagnosis were efficient.

PMID- 19406155
TI  - Simultaneous one-tube full-length amplification of the NA, NP, M, and NS genes of
      influenza A viruses for reverse genetics.
AB  - Reverse genetics of influenza A viruses has expedited increasingly basic research
      and vaccine development. Target-primed plasmid amplification using full-length
      PCR amplicons as inserts was established previously for strain-independent and
      rapid cloning of all eight influenza A virus genes. This method involves separate
      amplification of each viral gene using segment-specific primers. Four different
      primer pairs are required for PCR amplification of the neuraminidase gene
      depending on the subtype. In order to reduce the number of necessary PCRs, a pair
      of primers with truncated 3' ends was designed in the present study. This primer
      pair permitted reliable amplification of the NA, NP, M, and NS genes in one tube
      whose products can be separated subsequently by their sizes. Full-length
      amplicons can be generated with this one primer pair from the NA genes of all
      nine subtypes. By avoiding separate assays for several viral genes, this parallel
      PCR steps up rapid universal cloning of influenza A virus genes further.

PMID- 19406157
TI  - Characterization of an avian influenza virus H5N1 Egyptian isolate.
AB  - The highly pathogenic influenza virus H5N1 that infected chickens in Egypt in
      2006 was characterized at immunologic and molecular levels. Cloacal swabs from
      chicken were analyzed by rapid antigen detection and RT-PCR using H5- and N1
      specific primers, which confirmed the presence of an H5N1 influenza virus in
      infected chickens. Sequencing results revealed 100% homology of both genes with
      previously published sequences of H5N1 isolates from Egypt and the Middle East.
      The virus was isolated and propagated in MDBK cells in culture. Host cells showed
      a substantial cytopathic effect within 2 days of infection, which increased
      dramatically by the fourth day. Plaque infectivity titers of virus harvested from
      cell culture were initially 10(5)PFUs/ml and increased to 10(8)PFUs/ml after two
      additional passages and ultrafiltration. Formaldehyde treatment completely
      inactivated the virus, and MDBK cells inoculated with the killed virus showed no
      cytopathic effect. Two days after chickens were immunized with the killed virus,
      their sera showed that the killed Egyptian isolate was highly immunogenic.
      Western blot analysis showed that sera had antibodies reacting to four viral
      peptides: hemagglutinin (61.5kDa), RNA-binding protein (56kDa), neuraminidase
      (50kDa), and 45-kDa protein. In a challenge infection, the vaccine protected
      immunized chickens from death and reduced viral shedding.

PMID- 19406158
TI  - Replication reduction neutralization test, a quantitative RT-PCR-based technique
      for the detection of neutralizing hantavirus antibodies.
AB  - Hantaviruses, which are mainly rodent-borne viruses, cause hemorrhagic fever with
      renal syndrome in the Old World, and hantavirus pulmonary syndrome in the New
      World. A neutralization test based on quantitative RT-PCR, the replication
      reduction neutralization test (RRNT), was developed for efficient detection of
      hantavirus-neutralizing antibodies. The effectiveness of the RRNT was evaluated
      by examining several hantaviruses and hantavirus-specific convalescent human
      serum samples. All convalescent serum samples tested by RRNT caused significant
      decreases in hantavirus genomes with only one specific hantavirus species, which
      allowed a straightforward identification of the related hantavirus. The results
      obtained by RRNT were completely comparable with the results obtained by focus
      reduction neutralization test (FRNT). The RRNT approach is a reliable and rapid
      alternative for FRNT, hitherto considered as the gold standard for hantavirus
      serology.

PMID- 19406159
TI  - A novel, colorimetric neutralization assay for measuring antibodies to influenza
      viruses.
AB  - A colorimetric cell proliferation assay for measuring neutralizing antibodies to
      influenza viruses in human sera is described. Following a 90-min incubation, the
      serum-virus mixture was transferred to Madin-Darby canine kidney cells cultured
      in 96-well plates. After further incubation for three days, a tetrazolium salt
      was added to the wells. Cellular mitochondrial dehydrogenases cleave the
      tetrazolium salt to formazan, and the resulting color change is read by a
      spectrophotometer. The absorbance values correlate directly to the number of
      viable cells in the assay well and thus also to the neutralizing activity of
      influenza-specific antibodies present in the serum. With the few hands-on
      manipulations required, this assay allows simultaneous testing of a considerable
      number of sera, offers opportunities for automation, and is suitable for use
      under biosafety level-3 conditions. The test was used to study the antibody
      response after the administration of seasonal, inactivated, trivalent influenza
      vaccine. Antibody titers determined by the neutralization test in pre- and post
      vaccination serum pairs were compared with those obtained by the hemagglutination
      inhibition assay. The neutralization test yielded higher pre- and post
      vaccination titers and a larger number of significant increases in post
      vaccination antibody titer than the hemagglutination inhibition test. This new
      test format could serve as a valuable laboratory tool for influenza vaccine
      studies.

PMID- 19406161
TI  - Monitoring of human cytomegalovirus glycoprotein B genotypes using real-time
      quantitative PCR in immunocompromised Chinese patients.
AB  - Based on sequence variation in the N-terminus of glycoprotein B (gB), human
      cytomegalovirus (HCMV) can be classified into four gBn genotypes, and these
      genotypes are associated with different clinical outcomes. The distribution of
      gBn genotypes and the level of gBn DNA load were examined in immunocompromised
      Chinese patients using real-time quantitative PCR. In addition, the PCR and pp65
      antigenemia results were compared. In 1480 specimens, 81.4% were antigen
      positive, 12.6% were PCR-positive. The gB genotype distribution was as follows
      among PCR-positive samples: gBn1, 63.1%; gBn2, 13.4%; gBn3, 8.6%; gBn4, not
      detected; mixed genotypes, 14.9% (gBn1 and gBn3, 14.4%; gBn2 and gBn3, 0.5%). The
      gBn3 and gBn1 genotypes had the highest and lowest copy numbers, respectively
      (p<0.05). The quantity of gBn DNA found in PCR-positive, pp65-negative samples
      was significantly lower than that found in PCR-positive, pp65-positive samples
      (p<0.05). The PCR and antigenemia results did not differ among bone marrow
      transplant patients, solid organ transplant patients, and immunocompromised
      patients without transplantation (p>0.05). HCMV gBn genotyping using real-time
      quantitative PCR was established successfully, and the distribution of gBn
      genotypes in immunocompromised Chinese patients was investigated. This method may
      help to understand better the relationship between gBn genotype and clinical
      outcome and aid in clinical detection.

PMID- 19406160
TI  - Genetic variations in a well conserved 5'-untranslated region of hepatitis C
      virus genome isolated in Pakistan.
AB  - The diversity and extent of sequence variations between hepatitis C virus (HCV)
      isolates from Pakistan were studied and the probable effects of these variations
      were assessed on secondary viral structures. Sequencing and phylogenetic analysis
      was performed on 33 samples, of which 25 were typed as genotype 3 by RFLP
      (restriction fragment length polymorphism) and 8 remained unresolved. Rooted
      neighbour-joining (NJ) tree revealed that 28 isolates were HCV type 3a and 5
      isolates were typed as 3b. The majority of unresolved samples clustered in a
      different branch of genotype 3, supported by a bootstrap value of 71%. Another,
      cluster, cluster I, was found to have a bootstrap value of 81%. Genetic distance
      values showed significant diversity of isolates in these two clusters compared to
      the reference sequences. Pair-wise comparison showed the presence of additional
      restriction sites of HaeIII and RsaI in unresolved isolates. In conclusion,
      unique sequence variability was observed in the 5'-UTR of HCV type 3 isolates
      from Pakistan. One of the reasons for this sequence variability is the presence
      of mutations, which are additional restriction sites in the 5'-UTR. These
      mutations were also responsible for failure of conventional RFLP to type some of
      the HCV isolates.

PMID- 19406162
TI  - Baculovirus surface display of NS3 nonstructural protein of classical swine fever
      virus.
AB  - Classical swine fever virus (CSFV) causes significant losses in the pig industry
      in many countries. NS3 proteins of CSFV, which include serine protease and RNA
      helicase/nucleotide triphosphatase (NTPase) activities, are multifunctional
      proteins involved in polyprotein processing and viral replication. Previous
      reports showed that NS3 protein can induce apoptosis in host cells that present
      cytopathic effects (CPE). Baculovirus/insect cell systems are used widely for
      recombinant protein production. In this study, one recombinant baculovirus BacSC
      NS3 expressing histidine-tagged NS3 with the transmembrane domain (TM) and
      cytoplasmic domain (CTD) derived from baculovirus envelope protein gp64 of
      baculovirus was constructed. After infection, NS3 was expressed and anchored to
      the plasma membrane of Sf-9 cells, as demonstrated by Western blot assay and
      confocal microscopy. Immunogold electron microscopy demonstrated that the NS3
      glycoprotein successfully displayed on the baculoviral envelope. Animal vaccine
      tests showed that recombinant baculovirus BacSC-NS3 elicited significantly higher
      NS3 antibody titers in the treated mouse models than the control group. This
      report demonstrated the potential of NS3-pseudotyped baculovirus expression of
      NS3 protein successfully.

PMID- 19406163
TI  - Impact of hepatitis B virus genotypes and surface antigen variants on the
      performance of HBV real time PCR quantification.
AB  - Quantitative PCR assays used to monitor hepatitis B virus (HBV) load differ in
      their ability to detect different HBV variants. This study evaluated the
      performance of the Abbott RT PCR assay for quantitating DNA from different HBV
      genotypes and from HBV variants bearing HBsAg gene mutations. The study was
      performed on a randomly-selected sample with a viral load >6logIU/mL for each
      genotype and on 25 HBsAg variants. Each sample was assayed using the Abbott RT
      assay and with the Roche Cobas AmpliPrep-Cobas TaqMan as a reference method. All
      HBV genotypes were detected with the Abbott RT assay with an equivalent dynamic
      range (1-8logIU/mL). For each genotype, the data suggest that the assay was
      linear over the entire dilution range (r(2): 0.985-0.995). For the 25 HBsAg
      variants, viral titres determined with the two assays correlated well (r(2):
      0.929). The mean difference between the two methods was -0.295 (95% CI: -0.520 to
      -0.071). The difference was lower than 1log unit in all but two cases. In
      conclusion, the Abbott RT assay can detect and quantify DNA from different HBV
      variants with equivalent performance and is thus suitable for routine monitoring
      of patients with chronic HBV infections.

PMID- 19406164
TI  - Development of a primer-probe energy transfer real-time PCR assay for improved
      detection of classical swine fever virus.
AB  - Classical swine fever (CSF) is a contagious and devastating disease, causing
      serious losses in the pig industry worldwide. Vaccination of pigs with the
      conventional C-strain vaccine has been practised in different regions of the
      world in order to prevent the disease. In the control programmes of CSF, rapid
      detection and identification of the causing agent, classical swine fever virus
      (CSFV) is a crucial step. This study describes a novel real-time PCR assay based
      on primer-probe energy transfer (PriProET) technology for improved detection of
      CSFV. The assay is able to detect 20 copies of viral cDNA per reaction, showing a
      high sensitivity. The specificity has been evaluated by testing 57 pestiviruses,
      representing all species and unclassified pestiviruses. The assay has been found
      to be highly reproducible. Following PCR amplification, melting curve analysis
      allows confirmation of specific amplicons, and differentiation between wild-type
      CSFV and certain C-strain vaccines. This study provides a new tool for the
      diagnosis of CSF.

PMID- 19406165
TI  - Application of antibodies against nonstructural protein 2B of dengue serotype 2
      virus induced by DNA immunisation or recombinant protein NS 2B immunisation in
      BALB/c mice.
AB  - To investigate the structure and function of nonstructural (NS) protein 2B of the
      dengue serotype 2 virus (DV2) during infection, polyclonal antibodies (Abs)
      against DV2 NS2B were prepared by immunisation with NS2B protein or by DNA
      immunisation. The full-length NS2B gene was cloned and inserted into the
      prokaryotic expression vector pQE31, resulting in a vector, named pQE-NS2B, or
      into the eukaryotic expression vector pCAGGS-P7, resulting in the vector pCAG
      NS2B. The pQE-NS2B vector was transfected into Escherichia coli JM109, and
      recombinant NS2B protein was obtained by Ni(2+)-NTA agarose affinity
      chromatography. Vero cells transfected with pCAG-NS2B showed that NS2B protein
      can be expressed in eukaryotic cells. Finally, mice were immunised with the
      recombinant NS2B protein or pCAG-NS2B. Anti-NS2B sera from the immunised mice
      could specifically react with DV2 NS2B proteins, as visualised by fluorescence
      staining and Western blotting. Immunisation with NS2B protein induced a higher
      titre of the antibody than that induced by DNA immunisation. These data indicate
      that our antisera against DV2 NS2B can recognise both the natural and denatured
      NS2B protein. Based on these results, the polyclonal Abs could be used as a tool
      for studying the role of NS2B in the pathogenesis of DV2.

PMID- 19406166
TI  - Accurate single-day titration of adenovirus vectors based on equivalence of
      protein VII nuclear dots and infectious particles.
AB  - Protein VII is an abundant component of adenovirus particles and is tightly
      associated with the viral DNA. It enters the nucleus along with the infecting
      viral genome and remains bound throughout early phase. Protein VII can be
      visualized by immunofluorescent staining as discrete dots in the infected cell
      nucleus. Comparison between protein VII staining and expression of the 72kDa DNA
      binding protein revealed a one-to-one correspondence between protein VII dots and
      infectious viral genomes. A similar relationship was observed for a helper
      dependent adenovirus vector expressing green fluorescent protein. This
      relationship allowed accurate titration of adenovirus preparations, including
      wild-type and helper-dependent vectors, using a 1-day immunofluorescence method.
      The method can be applied to any adenovirus vector and gives results equivalent
      to the standard plaque assay.

PMID- 19406167
TI  - Detection and quantitation of Citrus leaf blotch virus by TaqMan real-time RT
      PCR.
AB  - A real-time RT-PCR assay based on the TaqMan chemistry was developed for reliable
      detection and quantitation of Citrus leaf blotch virus (CLBV) in citrus plants.
      Detection by this method was highly specific and about one thousand times more
      sensitive than detection by conventional RT-PCR. An external standard curve using
      in vitro synthesized RNA transcripts of the selected target allowed a
      reproducible quantitative assay, with a wide dynamic range (seven logarithmic
      units of concentration) and very low variation coefficient values. This protocol
      enabled detection of as little as 100 copies of CLBV RNA in various tissues and
      citrus varieties infected with CLBV sources from different geographical origins.
      The new assay greatly improves current detection methods for CLBV and it has been
      most helpful for the Spanish citrus sanitation, quarantine and certification
      programs, and fitness evaluation of infectious cDNA clones of CLBV, useful
      potentially as viral vectors for citrus.

PMID- 19406168
TI  - Broadly targeted multiprobe QPCR for detection of coronaviruses: Coronavirus is
      common among mallard ducks (Anas platyrhynchos).
AB  - Coronaviruses (CoVs) can cause trivial or fatal disease in humans and in animals.
      Detection methods for a wide range of CoVs are needed, to understand viral
      evolution, host range, transmission and maintenance in reservoirs. A new concept,
      "Multiprobe QPCR", which uses a balanced mixture of competing discrete non- or
      moderately degenerated nuclease degradable (TaqMan) probes was employed. It
      provides a broadly targeted and rational single tube real-time reverse
      transcription PCR ("NQPCR") for the generic detection and discovery of CoV.
      Degenerate primers, previously published, and the new probes, were from a
      conserved stretch of open reading frame 1b, encoding the replicase. This
      multiprobe design reduced the degree of probe degeneration, which otherwise
      decreases the sensitivity, and allowed a preliminary classification of the
      amplified sequence directly from the QPCR trace. The split probe strategy allowed
      detection of down to 10 viral nucleic acid equivalents of CoV from all known CoV
      groups. Evaluation was with reference CoV strains, synthetic targets, human
      respiratory samples and avian fecal samples. Infectious-Bronchitis-Virus (IBV)
      related variants were found in 7 of 35 sample pools, from 100 wild mallards (Anas
      platyrhynchos). Ducks may spread and harbour CoVs. NQPCR can detect a wide range
      of CoVs, as illustrated for humans and ducks.

PMID- 19406169
TI  - Schistosoma mansoni P-glycoprotein levels increase in response to praziquantel
      exposure and correlate with reduced praziquantel susceptibility.
AB  - One potential physiological target for new antischistosomals is the parasite's
      system for excretion of wastes and xenobiotics. P-glycoprotein (Pgp), a member of
      the ATP-binding-cassette superfamily of proteins, is an ATP-dependent efflux pump
      involved in transport of toxins and xenobiotics from cells. In vertebrates,
      increased expression of Pgp is associated with multidrug resistance in tumor
      cells. Pgp may also play a role in drug resistance in helminths. In this report,
      we examine the relationship between praziquantel (PZQ), the current drug of
      choice against schistosomiasis, and Pgp expression in Schistosoma mansoni. We
      show that levels of RNA for SMDR2, a Pgp homolog from S. mansoni, increase
      transiently in adult male worms following exposure to sub-lethal concentrations
      (100-500 nM) of PZQ. A corresponding, though delayed, increase in anti-Pgp
      immunoreactive protein expression occurs in adult males following exposure to
      PZQ. The level of anti-Pgp immunoreactivity in particular regions of adult worms
      also increases in response to PZQ. Adult worms from an Egyptian S. mansoni
      isolate with reduced sensitivity to PZQ express increased levels of SMDR2 RNA and
      anti-Pgp-immunoreactive protein, perhaps indicating a role for multidrug
      resistance proteins in development or maintenance of PZQ resistance.

PMID- 19406171
TI  - Regulation of epithelial apical junctions and barrier function by Galpha13.
AB  - The epithelial tight junction forms a barrier to paracellular solute movement. In
      this study we show that the heterotrimeric G-protein Galpha13 regulates the
      epithelial tight junction barrier. We generated MDCKII kidney epithelial cell
      lines in which the expression of an active Galpha13 mutant (Galpha13Q226L) could
      be induced. We demonstrated that Galpha13Q226L expression increased paracellular
      permeability and caused the disruption and redistribution of proteins comprising
      the tight junction and the adherens junction away from sites of cell contact and
      the appearance of basal stress fibers. The effects on the junctional proteins and
      the actin cytoskeleton were abrogated by the Rho kinase inhibitor Y27632 but not
      by the Src kinase inhibitor PP2. The Galpha13 mediated increase in permeability
      was also Src kinase independent but was partly dependent on Rho kinase
      signalling. Our data establish a link between Galpha13, Rho kinase signaling and
      epithelial barrier function and not only demonstrate that Galpha13 regulates
      epithelial apical junction properties but that it does so via signaling pathways
      that are distinct from the closely related protein Galpha12.

PMID- 19406173
TI  - Structural and functional bases for allosteric control of MMP activities: can it
      pave the path for selective inhibition?
AB  - The zinc-dependent matrix metalloproteinases (MMPs) belong to a large family of
      structurally homologous enzymes. These enzymes are involved in a wide variety of
      biological processes ranging from physiological cell proliferation and
      differentiation to pathological states associated with tumor metastasis,
      inflammation, tissue degeneration, and cell death. Controlling the enzymatic
      activity of specific individual MMPs by antagonist molecules is highly desirable,
      first, for studying their individual roles, and second as potential therapeutic
      agents. However, blocking the enzymatic activity with synthetic small inhibitors
      appears to be an extremely difficult task. Thus, this is an unmet need presumably
      due to the high structural homology between MMP catalytic domains. Recent reports
      have recognized a potential role for exosite or allosteric protein regions,
      distinct from the extended catalytic pocket, in mediating MMP activation and
      substrate hydrolysis. This raises the possibility that MMP enzymatic and non
      enzymatic activities may be modified via antagonist molecules targeted to such
      allosteric sites or to alternative enzyme domains. In this review, we discuss the
      structural and functional bases for potential allosteric control of MMPs and
      highlight potential alternative enzyme domains as targets for designing highly
      selective MMP inhibitors.

PMID- 19406170
TI  - Helminth immunoregulation: the role of parasite secreted proteins in modulating
      host immunity.
AB  - Helminths are masterful immunoregulators. A characteristic feature of helminth
      infection is a Th2-dominated immune response, but stimulation of immunoregulatory
      cell populations, such as regulatory T cells and alternatively activated
      macrophages, is equally common. Typically, Th1/17 immunity is blocked and
      productive effector responses are muted, allowing survival of the parasite in a
      "modified Th2" environment. Drug treatment to clear the worms reverses the
      immunoregulatory effects, indicating that a state of active suppression is
      maintained by the parasite. Hence, research has focussed on "excretory-secretory"
      products released by live parasites, which can interfere with every aspect of
      host immunity from initial recognition to end-stage effector mechanisms. In this
      review, we survey our knowledge of helminth secreted molecules, and summarise
      current understanding of the growing number of individual helminth mediators that
      have been shown to target key receptors or pathways in the mammalian immune
      system.

PMID- 19406172
TI  - Proteolytic and non-proteolytic roles of membrane type-1 matrix metalloproteinase
      in malignancy.
AB  - This manuscript provides an overview of the dynamic interactions which play an
      important role in regulating cancer cell functions. We describe and discuss,
      primarily, those interactions which involve membrane type-1 matrix
      metalloproteinase (MT1-MMP), its physiological inhibitor tissue inhibitor of
      metalloproteinases-2 (TIMP-2), furin-like proprotein convertases and the low
      density lipoprotein-related protein 1 (LRP1) signaling scavenger receptor. The
      interaction among these cellular proteins controls the efficiency of the
      activation of MT1-MMP and the unorthodox intracellular signaling which is
      generated by the catalytically inert complex of MT1-MMP with TIMP-2 and which
      plays a potentially important role in the migration of cancer cells. Our in-depth
      understanding of these cellular mechanisms may provide the key to solving the
      puzzling TIMP-2 paradox. This unsolved paradox arises from the fact that TIMP-2
      is a powerful inhibitor of MMPs including MT1-MMP, but at the same time high
      levels of TIMP-2 positively correlate with an unfavorable prognosis in cancer
      patients. Solving the TIMP-2 paradox may lead to solving a similar PAI-1 paradox
      and produce a clearer understanding of the biochemical mechanisms which control
      the functionality of the urokinase-type plasminogen activator*urokinase
      receptor*plasminogen activator inhibitor type-1 (uPAR*uPA*PAI-1) system in
      cancer.

PMID- 19406174
TI  - A dual mechanism of cytoprotection afforded by M-LDH in embryonic heart H9C2
      cells.
AB  - Muscle form of lactate dehydrogenase (M-LDH), a minor LDH form in cardiomyocytes,
      physically interacts with ATP-sensitive K+ (K ATP) channel-forming subunits.
      Here, we have shown that expression of 193gly-M-LDH, an inactive mutant of M-LDH,
      inhibit regulation of the K ATP channels activity by LDH substrates in embryonic
      rat heart H9C2 cells. In cells expressing 193gly-M-LDH chemical hypoxia has
      failed to activate K ATP channels. The similar results were obtained in H9C2
      cells expressing Kir6.2AFA, a mutant form of Kir6.2 with largely decreased K+
      conductance. Kir6.2AFA has slightly, but significantly, reduced cellular survival
      under chemical hypoxia while the deleterious effect of 193gly-M-LDH was
      significantly more pronounced. The levels of total and subsarcolemmal ATP in H9C2
      cells were not affected by Kir6.2AFA, but the expression of 193gly-M-LDH led to
      lower levels of subsarcolemmal ATP during chemical hypoxia. We conclude that M
      LDH regulates both the channel activity and the levels of subsarcolemmal ATP and
      that both mechanism contribute to the M-LDH-mediated cytoprotection.

PMID- 19406175
TI  - Japanese encephalitis virus-based replicon RNAs/particles as an expression system
      for HIV-1 Pr55 Gag that is capable of producing virus-like particles.
AB  - Ectopic expression of the structural protein Pr55(Gag) of HIV-1 has been limited
      by the presence of inhibitory sequences in the gag coding region that must
      normally be counteracted by HIV-1 Rev and RRE. Here, we describe a cytoplasmic
      RNA replicon based on the RNA genome of Japanese encephalitis virus (JEV) that is
      capable of expressing HIV-1 gag without requiring Rev/RRE. This replicon system
      was constructed by deleting all three JEV structural protein-coding regions (C,
      prM, and E) from the 5'-proximal region of the genome and simultaneously
      inserting an HIV-1 gag expression cassette driven by the internal ribosome entry
      site of encephalomyocarditis virus into the 3'-proximal noncoding region of the
      genome. Transfection of this JEV replicon RNA led to expression of Pr55(Gag) in
      the absence of Rev/RRE in the cytoplasm of hamster BHK-21, human HeLa, and mouse
      NIH/3T3 cells. Production of the Pr55(Gag) derived from this JEV replicon RNA
      appeared to be increased by approximately 3-fold when compared to that based on
      an alphavirus replicon RNA. Biochemical and morphological analyses demonstrated
      that the Pr55(Gag) proteins were released into the culture medium in the form of
      virus-like particles. We also observed that the JEV replicon RNAs expressing the
      Pr55(Gag) could be encapsidated into single-round infectious JEV replicon
      particles when transfected into a stable packaging cell line that provided the
      three JEV structural proteins in trans. This ectopic expression of the HIV-1
      Pr55(Gag) by JEV-based replicon RNAs/particles in diverse cell types may
      represent a useful molecular platform for various biological applications in
      medicine and industry.

PMID- 19406177
TI  - Inhibition of endoplasm reticulum stress by ghrelin protects against
      ischemia/reperfusion injury in rat heart.
AB  - Ghrelin is a multi-functional polypeptide with cardiovascular protective effects.
      We aimed to explore whether the cardioprotective effect of ghrelin is mediated by
      inhibiting myocardial endoplasmic reticulum stress (ERS). A Langendorff model of
      isolated rat heart was used with ischemia/reperfusion (I/R; 40/120 min). Cardiac
      function was monitored, and histomorphologic features, degree of myocardial
      injury, level of ERS markers, and number of apoptotic cardiomyocytes were
      determined. Compared with control group, the I/R group showed significantly
      decreased cardiac function, seriously damaged myocardial tissue, increased number
      of apoptotic cells, and overexpression of mRNA and protein of ERS markers.
      However, preadministration of ghrelin in vivo (10(-8)mol/kg, intraperitoneal
      injection, every 12h, twice in all) greatly ameliorated the damaged heart
      function, attenuated myocardial injury and apoptosis, and decreased the
      expression of ERS markers: it decreased the mRNA and protein levels of glucose
      regulated protein78 (GRP78) and C/EBP homologous protein (CHOP), with reduced
      caspase-12 protein expression. Furthermore, in vitro, ghrelin directly inhibited
      the myocardial ERS response induced by tunicamycin or dithiothreitol in rat
      cardiac tissue. Ghrelin could protect the heart against I/R injury, at least in
      part, through inhibiting myocardial ERS.

PMID- 19406178
TI  - Ouabain evokes exocytosis dependent on ryanodine and mitochondrial calcium stores
      that is not followed by compensatory endocytosis at the neuromuscular junction.
AB  - Ouabain is a cardiotonic glycoside that inhibits the sodium potassium ATPase pump
      leading to sodium accumulation in nerve terminals. At the frog neuromuscular
      junction, ouabain induces acetylcholine release and a rapid depletion of synaptic
      vesicles. In the present work, we used FM1-43 vital labeling to dissect the
      effect of ouabain on synaptic vesicles recycling. We first examined images of
      nerve-muscle preparations that were stained with FM1-43 by electrical stimulation
      of the nerve and destained with ouabain. We observed that ouabain induced
      exocytosis of synaptic vesicles independently of extracellular calcium, implying
      a mechanism of exocytosis that can bypass the requirement for extracellular
      calcium. We therefore tested the hypothesis that ouabain induces exocytosis by
      mobilizing intracellular calcium and we report that calcium release from
      endoplasmic reticulum through ryanodine receptors is necessary for ouabain-evoked
      exocytosis. In addition, the ouabain-evoked exocytosis was dependent on calcium
      released from mitochondria. We also investigated if exocytosis evoked by ouabain
      is followed by compensatory endocytosis. We observed that muscles incubated with
      FM1-43 in the presence of ouabain did not present significant staining. In
      conclusion, our data demonstrate that exocytosis evoked by ouabain is independent
      on extracellular calcium but dependent on calcium release from endoplasmic
      reticulum and mitochondrial stores. In addition, we suggest that ouabain can be
      used as a pharmacological tool to uncouple synaptic vesicles exocytosis from
      endocytosis at the neuromuscular junction.

PMID- 19406176
TI  - Genetic diversity of the ORF5 gene of porcine reproductive and respiratory
      syndrome virus isolates in China from 2006 to 2008.
AB  - Since April 2006, swine herds have experienced the outbreaks of a highly
      pathogenic porcine reproductive and respiratory syndrome (PRRS) in China. To
      explore the possible mechanism of the emergence of the highly pathogenic PRRS and
      more fully understand the extent of genetic diversity of PRRSV in China, we
      analyzed the ORF5 gene sequences of 159 representative PRRSV isolates in 16
      provinces from 2006 to 2008. Sequence and phylogenetic analyses showed that all
      these 159 isolates belonged to the North American genotype and were further
      divided into six subgenotypes; 140 of 159 isolates were closely related to the
      highly pathogenic PRRSV with 98.5-100% nucleotide and 98.3-100% amino acid
      sequence identities and belonged to Subgenotype I; and 3, 8, 4, 3, 1 of 159
      isolates were part of Subgenotypes II-VI, respectively. Amino acid analysis of
      the GP5 protein revealed that all the isolates in Subgenotypes I-III were found
      to be highly variable in the primary neutralizing epitope; most of the isolates
      in Subgenotypes I and IV had more glycosylation sites than those in Subgenotypes
      II, III, V and VI; and 1, 5, and 9 unique amino acid mutations were observed in
      Subgenotypes I, IV and VI, respectively. In conclusion, our study provides the
      evidence of coexistence of six different subgenotype isolates in pigs in China
      from 2006 to 2008, and emphasizes the importance of reinforcing PRRSV
      surveillance, especially after the emergence of highly pathogenic PRRS in China.

PMID- 19406179
TI  - The autoimmunity-related polymorphism PTPN22 1858C/T is associated with anti
      titin antibody-positive myasthenia gravis.
AB  - Genetic variation in the intracellular tyrosine phosphatase PTPN22 has been
      recently associated with susceptibility to various autoimmune diseases.
      Myasthenia gravis (MG) is a complex genetic disease with a distinct clinical and
      pathological heterogeneity. We conducted a case-control association study for the
      PTPN22 1858C/T polymorphism in Hungarian and German MG patients (n = 282) and
      regional controls (n = 379). We detected an association of the PTPN22 1858T
      allele with MG in the subgroup of nonthymoma patients with anti-titin antibodies
      present (n = 50; T allele frequency 21% vs 11% in controls; p = 0.005, odds ratio
      2.1, 95% confidence interval 1.23-3.58). This overrepresentation was reported
      independently in both Hungarian and German MG patients compared with regional
      controls. We conclude that the common autoimmune polymorphism PTPN22 1858C/T may
      account for disease susceptibility in a subset of nonthymoma MG patients with
      anti-titin antibodies present.

PMID- 19406180
TI  - A pcDNA-Ehcpadh vaccine against Entamoeba histolytica elicits a protective Th1
      like response in hamster liver.
AB  - DNA vaccines are promising tools to fight parasitic diseases, including
      amoebiasis caused by the protozoan Entamoeba histolytica. Here we studied the
      immunogenicity and protective efficacy of a DNA vaccine against this parasite
      composed by the EhCPADH surface complex encoding genes (Ehcp112 and Ehadh112).
      EhCPADH is formed by an adhesin (EhADH112) and a cysteine proteinase (EhCP112),
      both involved in the parasite virulence. We evaluated transcription, protein
      expression, immunological response and protection against hepatic amoebiasis in
      hamsters intradermally and intramuscularly immunized with a mixture of pcDNA
      Ehadh112 and pcDNA-Ehcp112 plasmids. RT-PCR and immunohistochemical assays showed
      that both antigens were differentially expressed in spleen and liver of immunized
      animals. No significant antibody immune response was induced by either route.
      However, intradermally inoculated hamsters presented a robust Th1-like immune
      response, characterized by high levels of INF-gamma and TNF-alpha cytokines,
      detected in the liver of animals challenged with virulent trophozoites. Animals
      showed significant protection against amoebiasis manifested by a higher survival
      rate and a significant prevention of liver abscess formation. We conclude that a
      refinement of this DNA vaccine could be a good choice to control hepatic
      amoebiasis.

PMID- 19406181
TI  - Alternative vaccination locations: who uses them and can they increase flu
      vaccination rates?
AB  - Since many unvaccinated individuals do not regularly contact the traditional
      health care system, we sought to determine the role that alternative vaccination
      locations (e.g., workplaces and retail clinics) could play in increasing
      influenza vaccination coverage. Between February 14, 2008 and March 10, 2008, a
      25-question influenza vaccine questionnaire was administered to a nationally
      representative, stratified sample of panelists. Our results found that while
      alternative locations are covering some segments not captured by the traditional
      health care system (e.g., younger, working, white individuals in metropolitan
      areas), they are not serving many other segments (e.g., minority, rural, or lower
      income patients).

PMID- 19406183
TI  - Sialivac: an intranasal homologous inactivated split virus vaccine containing
      bacterial sialidase for the control of avian influenza in poultry.
AB  - A simple, effective inactivated avian flu vaccine composed of three homologous
      highly pathogenic (HP) H5N1 strains combined with Clostridium perfringens type A
      107 sialidase/neuramindase and chitosan as a trans epithelial carrier adjuvant
      applied intranasally to poultry is described. Poultry were vaccinated with an
      inactivated, solvent split, chitosan adjuvanted intranasal (IN) vaccine with and
      without C. perfringens sialidase and the resulting serum IgG antibody measured by
      haemagglutination inhibition (HI) and mucosal IgA by ELISA. The clinical
      effectiveness was demonstrated by disease intervention field trials, where the
      ability of an intranasal vaccine containing three homologous inactivated solvent
      split HP H5N1 strains, C. perfringens sialidase and chitosan was successful in
      controlling the disease in intensively reared commercial chickens. Evidence is
      presented by demonstrating effective intervention with IN vaccine during
      outbreaks in poultry previously vaccinated with commercial heterologous H5N2
      intramuscular (IM) vaccine and reassorted H5N1 Re-1 vaccine which had failed to
      protect intensively reared birds. Intervention with the IN vaccine in such flocks
      completely halted the infection within 2-5 days. Survivors ceased to excrete live
      virus. Stimulation of the common mucosal immune system (CMIS) and the early
      production of secretory IgA and subsequently humoral IgG demonstrated by
      laboratory controlled experiments and field studies revealed the ability of
      intranasally vaccinated birds to resist lethal virus challenge. A strategy of
      mucosal immunisation is recommended to reduce the incidence of disease in
      intensively reared poultry and thus minimise the generation and transfer of
      mutated highly pathogenic subtypes to humans and other animals.

PMID- 19406182
TI  - Single- and multiple-clade influenza A H5N1 vaccines induce cross protection in
      ferrets.
AB  - The rapid evolution, genetic diversity, broad host range, and increasing human
      infection with avian influenza A (H5N1) viruses highlight the need for an
      efficacious cross-clade vaccine. Using the ferret model, we compared induction of
      cross-reactive immunity and protective efficacy of three single-clade H5N1
      vaccines and a novel multiple-clade H5N1 vaccine, with and without MF59 adjuvant.
      Reverse genetics (rg) was used to generate vaccine viruses containing the
      hemagglutinin (HA) and neuraminidase genes of wild-type H5N1 viruses. Ferrets
      received two doses of inactivated whole-virus vaccine separated by 3 weeks.
      Single-clade vaccines (7.5 microg HA per dose) included rg-A/Vietnam/1203/04
      (clade 1), rg-A/Hong Kong/213/03 (clade 1), and rg-A/Japanese White Eye/Hong
      Kong/1038/06 (clade 2.3). The multiple-clade vaccine contained 3.75 microg HA per
      dose of each single-clade vaccine and of rg-A/Whooper Swan/Mongolia/244/05 (clade
      2.2). Two doses of vaccine were required to substantially increase anti-HA and
      virus neutralizing antibody titers to H5N1 viruses. MF59 adjuvant enhanced
      induction of clade-specific and cross-clade serum antibody responses, reduced
      frequency of infection (as determined by upper respiratory tract virus shedding
      and seroconversion data), and eliminated disease signs. The rg-A/Hong Kong/213/03
      vaccine induced the highest antibody titers to homologous and heterologous H5N1
      viruses, while rg-A/Japanese White Eye/Hong Kong/1038/06 vaccine induced the
      lowest. The multiple-clade vaccine was broadly immunogenic against clade 1 and 2
      viruses. The rg-A/Vietnam/1203/04 vaccine (the currently stockpiled H5N1 vaccine)
      most effectively reduced upper respiratory tract virus shedding after challenge
      with clade 1 and 2 viruses. Importantly, all vaccines protected against lethal
      challenge with A/Vietnam/1203/04 virus and provided cross-clade protection.

PMID- 19406184
TI  - Report of the 5th meeting on the evaluation of pandemic influenza prototype
      vaccines in clinical trials: World Health Organization, Geneva, Switzerland, 12
      13 February 2009.
AB  - Influenza vaccines are potentially the most efficacious means of mitigating the
      impact of influenza pandemic and might contribute to the rapid containment of an
      emerging pandemic virus. On the 12-13 February 2009, the Initiative For Vaccine
      Research (IVR) of the World Health Organisation convened the 5th meeting on the
      'Evaluation of pandemic influenza prototype vaccines in clinical trials' in
      Geneva. This was a follow-up meeting to the 4th meeting held on 14-15 February
      2008 [Girard M, Palkonyay L, Kieny MP. Report of the 4th meeting on the
      evaluation of pandemic influenza prototype vaccines in clinical trials. Vaccine
      2008;26:4975-7], and presentations were made by representatives from industry,
      academia, and governmental organisations. This year's meeting aimed to update the
      progress made during the past year on H5N1 and other prototype pandemic vaccines
      that have undergone clinical trials. A number of vaccine types were covered,
      including classical egg-derived inactivated vaccines, cell-derived inactivated
      vaccines, live-attenuated vaccines (LAIV) and vaccines developed using new
      technologies. The effects of different adjuvants and prime-boosting schedules
      were important topics, and further data were presented to show that children
      mount vigorous antibody responses to several H5N1 vaccines. Other subjects
      presented and discussed were standardisation, and regulatory issues concerning
      pandemic vaccines.

PMID- 19406185
TI  - c-di-GMP as a vaccine adjuvant enhances protection against systemic methicillin
      resistant Staphylococcus aureus (MRSA) infection.
AB  - Cyclic diguanylate (c-di-GMP) is a novel immunomodulator and immune enhancer that
      triggers a protective host innate immune response. The protective effect of c-di
      GMP as a vaccine adjuvant against Staphylococcus aureus infection was
      investigated by subcutaneous (s.c.) vaccination with two different S. aureus
      antigens, clumping factor A (ClfA) and a nontoxic mutant staphylococcal
      enterotoxin C (mSEC), then intravenous (i.v.) challenge with viable methicillin
      resistant S. aureus (MRSA) in a systemic infection model. Mice immunized with c
      di-GMP plus mSEC or c-di-GMP plus ClfA vaccines then challenged with MRSA
      produced strong antigen-specific antibody responses demonstrating immunogenicity
      of the vaccines. Bacterial counts in the spleen and liver of c-di-GMP plus mSEC
      and c-di-GMP plus ClfA-immunized mice were significantly lower than those of
      control mice (P<0.001). Mice immunized with c-di-GMP plus mSEC or c-di-GMP plus
      ClfA showed significantly higher survival rates at day 7 (87.5%) than those of
      the non-immunized control mice (33.3%) (P<0.05). Furthermore, immunization of
      mice with c-di-GMP plus mSEC or c-di-GMP plus ClfA induced not only very high
      titers of immunoglobulin G1 (IgG1), but c-di-GMP plus mSEC also induced
      significantly higher levels of IgG2a, IgG2b and IgG3 compared to alum adjuvant
      (P<0.01 and P<0.001, respectively) and c-di-GMP plus ClfA induced significantly
      higher levels of IgG2a, IgG2b and IgG3 compared to alum adjuvant (P<0.001). Our
      results show that c-di-GMP should be developed as an adjuvant and
      immunotherapeutic to provide protection against systemic infection caused by S.
      aureus (MRSA).

PMID- 19406186
TI  - Directed molecular evolution improves the immunogenicity and protective efficacy
      of a Venezuelan equine encephalitis virus DNA vaccine.
AB  - We employed directed molecular evolution to improve the cross-reactivity and
      immunogenicity of the Venezuelan equine encephalitis virus (VEEV) envelope
      glycoproteins. The DNA encoding the E1 and E2 proteins from VEEV subtypes IA/B
      and IE, Mucambo virus (MUCV), and eastern and western equine encephalitis viruses
      (EEEV and WEEV) were recombined in vitro to create libraries of chimeric genes
      expressing variant envelope proteins. ELISAs specific for all five parent viruses
      were used in high-throughput screening to identify those recombinant DNAs that
      demonstrated cross-reactivity to VEEV, MUCV, EEEV, and WEEV after administration
      as plasmid vaccines in mice. Selected variants were then used to vaccinate larger
      cohorts of mice and their sera were assayed by both ELISA and by plaque reduction
      neutralization test (PRNT). Representative variants from a library in which the
      E1 gene from VEEV IA/B was held constant and only the E2 genes of the five parent
      viruses were recombined elicited significantly increased neutralizing antibody
      titers to VEEV IA/B compared to the parent DNA vaccine and provided improved
      protection against aerosol VEEV IA/B challenge. Our results indicate that it is
      possible to improve the immunogenicity and protective efficacy of alphavirus DNA
      vaccines using directed molecular evolution.

PMID- 19406187
TI  - Modulation of carcinogen bioavailability by immunisation with benzo[a]pyrene
      conjugate vaccines.
AB  - Benzo[a]pyrene (B[a]P) conjugate vaccines based on ovalbumin, tetanus toxoid and
      diphtheria toxoid (DT) as carrier proteins were developed to investigate the
      effect of specific antibodies on the bioavailability of this ubiquitous
      carcinogen and its metabolites. After metabolic activation of this prototype
      carcinogen, B[a]P forms DNA adducts which initiate chemical carcinogenesis. B[a]P
      DT conjugate induced the most robust immune response. The antibodies reacted not
      only with B[a]P but also with the proximate carcinogen 7,8-diol-B[a]P. Antibodies
      modulated the bioavailability of B[a]P and its metabolic activation in a dose
      dependent manner by sequestration in the blood. Our results showed that this
      immune prophylactic strategy influences the pharmacokinetic of B[a]P and further
      studies to investigate their effects on chemical carcinogenesis are warranted.

PMID- 19406189
TI  - Efficacy of three inactivated vaccines against bluetongue virus serotype 8 in
      sheep.
AB  - Bluetongue has become a major animal health issue in the European Union. The
      member states and Switzerland have agreed on a vaccination strategy. Three
      different inactivated monovalent vaccines against bluetongue virus serotype 8
      were selected for the compulsory vaccination program carried out in Germany in
      2008. The efficacy of these vaccines was evaluated in a pilot study in sheep
      immunised under field conditions by clinical, virological and serological
      examination before and after experimental challenge infection with a BTV-8 field
      isolate. Antibody levels prior to challenge infection differed between the
      vaccinated groups, but all seroconverted animals were fully protected against
      clinical disease and virus replication. Only one vaccinated animal was very
      weakly positive in the real-time RT-PCR at day 10 after challenge infection, and
      one seronegative sheep in one of the vaccine groups was not protected.

PMID- 19406190
TI  - Reduction in the incidence of invasive pneumococcal disease after general
      vaccination with 7-valent pneumococcal conjugate vaccine in Germany.
AB  - General vaccination with the 7-valent pneumococcal conjugate vaccine was
      recommended in Germany in July 2006 for all children <2 years. The proportion of
      reported invasive pneumococcal disease (IPD) caused by vaccine serotypes before
      vaccine introduction was considerably lower than in the US. We report data from
      nationwide surveillance of IPD in children with two reporting sources, pediatric
      hospitals and microbiological laboratories in Germany. Incidence rates with
      regard to age groups and pneumococcal serotypes are based on capture recapture
      estimates combining the two reporting sources. Between July 1, 1997 and June 30,
      2003, 2680 cases (an average 447 yearly cases) of IPD were observed in children
      <16 years in Germany compared to 223 cases between July 1, 2007 and June 30,
      2008. A significant reduction in overall incidence (4/100,000-3.2/100,000) was
      attributed to significant reductions in children younger than 2 years
      (20.0/100,000-11.0/100,000). While the incidence of all serotypes included in the
      vaccine was reduced in the age group <2 years, the incidence of non-vaccine
      serotypes remained stable. These data show a first success of the pneumococcal
      vaccination program in Germany. Further changes in incidence and serotype
      distribution of IPD are subject to future surveillance.

PMID- 19406188
TI  - Cationic lipid/DNA complexes (JVRS-100) combined with influenza vaccine (Fluzone)
      increases antibody response, cellular immunity, and antigenically drifted
      protection.
AB  - Safe and effective adjuvants for influenza vaccines that could increase both the
      levels of neutralizing antibody, including against drifted viral subtypes, and T
      cell immunity would be a major advance in vaccine design. The JVRS-100 adjuvant,
      consisting of DOTIM/cholesterol cationic liposome-DNA complexes, is particularly
      promising for vaccines that require induction of high levels of antibody and T
      cell immunity, including CD8(+) cytotoxic T lymphocytes (CTL). Inclusion of
      protein antigens with JVRS-100 results in the induction of enhanced humoral and
      cell-mediated (i.e., CD4(+) and CD8(+) T cells) immune responses. The JVRS-100
      adjuvant combined with a split trivalent influenza vaccine (Fluzone-sanofi
      pasteur) elicited increased antibody and T-cell responses in mice and non-human
      primates compared to vaccination with Fluzone alone. Mice vaccinated with JVRS
      100-Fluzone and challenged with antigenically drifted strains of H1N1 (PR/8/34)
      and influenza B (B/Lee/40) viruses had higher grade protection, as measured by
      attenuation of weight loss and increased survival, compared to recipients of
      unadjuvanted vaccine. The results indicate that the JVRS-100 adjuvant
      substantially increases immunogenicity and protection from drifted-strain
      challenge using an existing influenza vaccine.

PMID- 19406191
TI  - Effect of the carthamins yellow from Carthamus tinctorius L. on hemorheological
      disorders of blood stasis in rats.
AB  - Hemorheological disorders may play an important role in the pathogenesis and
      development of many diseases. Blood stasis, i.e. the decrease of blood flow
      velocity, indicates hemorheological abnormalities. The carthamins yellow (CY),
      isolated from Carthamus tinctorius L., has been extensively used as a natural
      food colorant. We investigated the effects of CY on a blood stasis model, which
      was obtained by placing rats in ice-cold water during the time interval between
      two injections of epinephrine. The results demonstrated that the CY significantly
      decreased the whole blood viscosity, plasma viscosity, and erythrocyte
      aggregation index, which were increased in the blood stasis model. Hematocrit and
      platelet aggregation were reduced, while prothrombin time was delayed with
      increasing doses of CY. Therefore, CY administration might provide the additional
      benefit of increasing blood fluidity by lowering blood viscosity, which can be of
      great value in the prevention of hemorheological disorder-associated diseases in
      at risk patients. Meanwhile, the mild activities of antiplatelet aggregation and
      anticoagulation induced by CY should be considered, if these relatively untoward
      symptoms occurred when the hemorrhagic patients ate food colored by CY. However
      the small amounts used in food are highly unlikely to cause adverse effects.

PMID- 19406192
TI  - Effect of taurine supplementation on cytochrome P450 2E1 and oxidative stress in
      the liver and kidneys of rats with streptozotocin-induced diabetes.
AB  - To investigate whether diabetes-induced alterations of CYP2E1 and oxidative
      stress can be modulated by dietary taurine supplementation, male Wistar rats were
      divided into non-diabetic, diabetic, and diabetic taurine-supplemented groups
      (administered at 2% in the drinking water). Increased levels of CYP2E1-catalyzed
      p-nitrophenol hydroxylation were found in liver and kidney microsomes of rats
      with STZ-induced diabetes compared to those of non-diabetic control rats.
      Immunoblot and RT-PCR analyses of CYP2E1 protein and mRNA levels in the liver and
      kidneys showed the same trend as with enzyme activities. Taurine supplementation
      significantly decreased the enzyme activity and expression (protein and mRNA) of
      CYP2E1 in diabetic rat kidneys. Plasma beta-hydroxybutyrate concentration was
      significantly reduced in taurine-treated diabetic rats. The induction of heme
      oxygenase-1 mRNA was suppressed by taurine treatment in diabetic rat kidneys. An
      increase in reduced glutathione (GSH) and a higher ratio of reduced to oxidized
      glutathione (GSH/GSSG) together with lower values of thiobarbituric acid-reactive
      substances (TBARS) were observed in the kidneys of taurine-treated diabetic rats.
      However, taurine supplementation caused only a slight or insignificant effect on
      these alternations in the liver of diabetic rats. Our results show dietary
      taurine may reduce CYP2E1 expression and activity, and oxidative stress in
      kidneys of diabetic rats.

PMID- 19406193
TI  - Influence of Helicteres isora administration for diabetes mellitus: Its effect on
      erythrocyte membrane and antioxidant status.
AB  - In this study the effect of Helicteres isora L. on erythrocyte membrane bound
      enzymes and antioxidants activity in plasma and erythrocytes of streptozotocin
      (STZ) induced diabetic model was investigated. The aqueous bark extract of H.
      isora was administered orally for 30 days to control and STZ induced diabetic
      rats. The effect of bark extract on glucose, insulin, haemoglobin, glycosylated
      haemoglobin, TBARS, hydroperoxide, superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxide (GPx), glutathione-S-transferase (GST), vitamins C and E,
      reduced glutathione (GSH) and membrane bound enzymes were studied. The levels of
      glucose, glycosylated haemoglobin, TBARS, hydroperoxide, and vitamin E were
      increased significantly whereas the level of insulin, haemoglobin, as well as
      antioxidants, membrane bound total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase and
      Mg(2+)-ATPase were decreased significantly in STZ diabetic rats. Administration
      of bark extract to diabetic rats showed a decrease in the levels of glucose,
      glycosylated haemoglobin, lipid peroxidation markers and vitamin E. In addition
      the levels of insulin, haemoglobin, enzymatic antioxidants, vitamin C, and GSH
      and the activities of membrane bound enzymes also were increased in H. isora
      treated diabetic rats. The present study indicates that the H. isora possesses a
      significant favourable effect on erythrocyte membrane bound enzymes and
      antioxidants defense system in addition to its antidiabetic effect.

PMID- 19406194
TI  - Concomitant administration of sodium 2,3-dimercapto-1-propanesulphonate (DMPS)
      and diphenyl diselenide reduces effectiveness of DMPS in restoring damage induced
      by mercuric chloride in mice.
AB  - The effect of combined therapy with diphenyl diselenide (PhSe)(2) and sodium 2,3
      dimercapto-propane-1-sulphonate (DMPS) against alterations induced by mercury
      (Hg(2+)) was evaluated. Mice were exposed to mercuric chloride (HgCl(2)) (1mg/kg,
      subcutaneously) for two weeks. After that, mice received (PhSe)(2) (15.6 mg/kg),
      or DMPS (12.6 mg/kg), or a combination of both for one week. Thiobarbituric acid
      reactive substances (TBARS), ascorbic acid and Hg(2+) levels and glutathione S
      transferase (GST) and catalase (CAT) activities were carried out in kidney.
      Hematological parameters, plasmatic bilirubin, uric acid, urea and creatinine
      levels as well as lactate dehydrogenase (LDH) activity were determined. (PhSe)(2)
      or DMPS restored the increase in LDH activity and TBARS, bilirubin, uric acid,
      urea and creatinine levels caused by HgCl(2). The levels of erythrocytes,
      hemoglobin and hematocrit reduced by HgCl(2) exposure were restored by (PhSe)(2)
      or DMPS administration in mice. Leukocyte and platelet counts modified by HgCl(2)
      exposure were restored by (PhSe)(2) or DMPS therapy. DMPS restored the increase
      in Hg(2+) levels induced by exposure to HgCl(2). Concomitant administration of
      (PhSe)(2) and DMPS reduced the effectiveness of DMPS in restoring damage induced
      by HgCl(2). Combined therapy with (PhSe)(2) and DMPS was less effective than
      isolated therapies in restoring the damage induced by HgCl(2) in mice.

PMID- 19406195
TI  - Toxic and essential trace elemental contents in fish species from the Black Sea,
      Turkey.
AB  - Toxic and essential element content of ten different fish species from the Black
      Sea were determined by atomic absorption spectrometry after microwave digestion
      method. The validation of the presented procedure is performed by the analysis of
      standard reference materials (NRCC-DORM 2 Dogfish Muscle). The relative standard
      deviations were found to be lower than 10%. Toxic element content in fish samples
      were found 25-84 microg/kg for mercury, 0.11-0.32 microg/g for arsenic, 0.28-0.87
      microg/g for lead, 0.10-0.35 microg/g for cadmium, 1.14-3.60 microg/g for nickel.
      Trace element content in fish samples were found 36.2-145 microg/g for iron, 0.65
      2.78 microg/g for copper, 2.76-9.10 microg/g for manganese, 38.8-93.4 microg/g
      for zinc, 0.19-0.85 microg/g for selenium, 0.63-1.74 microg/g for chromium. The
      levels of lead and cadmium in fish samples were higher than the recommended legal
      limits for human consumption.

PMID- 19406196
TI  - Macranthoside B, a hederagenin saponin extracted from Lonicera macranthoides and
      its anti-tumor activities in vitro and in vivo.
AB  - Macranthoside B (MB) is a hederagenin saponin extracted from the flower bud of
      Lonicera macranthoides. In this study, we defined the anticancer effect of MB
      both in vitro and in vivo using cell proliferation assays and xenograft tumor
      growth assays. Our data indicate that MB inhibits the proliferation of various
      kinds of cancer cells with IC(50) values in the range of 10-20 microM. Moreover,
      the volume and weight of xenograft tumors in nude mice treated with 5mg/kgMB were
      decreased remarkably compared to those of the vehicle control group. Furthermore,
      DAPI staining and flow cytometry analysis with Annexin V/PI double staining
      revealed that more apoptotic cells were observed following MB treatment. In
      addition, degradation of PARP (poly-ADP-ribose polymerase), and activation of the
      caspase cascade for intrinsic pathways were observed. We also found that the
      expression of Bcl-2 protein decreased and the protein level of Bax increased
      which leading to an increase of the Bax/Bcl-2 ratio. Our results showed that MB
      exhibited strong anti-tumor effect and mitochondrion-mediated apoptosis induction
      involved in it.

PMID- 19406198
TI  - Lack of genoprotective effect of phytosterols and conjugated linoleic acids on
      Caco-2 cells.
AB  - Much interest has focused on the cholesterol-lowering effects of phytosterols
      (plant sterols) but limited data suggests they may also possess anti-carcinogenic
      activity. Conjugated linoleic acids (CLA), sourced from meat and dairy products
      of ruminant animals, has also received considerable attention as a potential anti
      cancer agent. Therefore, the aims of this project were to (i) examine the effects
      of phytosterols and CLA on the viability and growth of human intestinal Caco-2
      cells and (ii) determine their potential genoprotective (comet assay), COX-2
      modulatory (ELISA) and apoptotic (Hoechst staining) activities. Caco-2 cells were
      supplemented with the phytosterols campesterol, beta-sitosterol, or beta
      sitostanol, or a CLA mixture, or individual CLA isomers (c10t12-CLA, t9t11-CLA)
      for 48 h. The three phytosterols, at the highest levels tested, were found to
      reduce both the viability and growth of Caco-2 cells while CLA exhibited isomer
      specific effects. None of the phytosterols protected against DNA damage. At a
      concentration of 25 microM, both c10t12-CLA and t9t11-CLA enhanced (P<0.05)
      oxidant-induced, but not mutagen-induced, DNA damage. Neither the phytosterols
      nor CLA induced apoptosis or modulated COX-2 production. In conclusion,
      campesterol, beta-sitosterol, beta-sitostanol, c10t12-CLA, and t9t11-CLA were not
      toxic to Caco-2 cells, at the lower levels tested, and did not exhibit potential
      anti-carcinogenic activity.

PMID- 19406197
TI  - Human health risk of polychlorinated biphenyls and organochlorine pesticides
      resulting from seafood consumption in South Korea, 2005-2007.
AB  - Organochlorines (OCs) such as polychlorinated biphenyls (PCBs) and organochlorine
      pesticides (OCPs), were measured in 26 species of seafood commonly consumed by
      the Korean population. PCBs and DDTs were the predominant contaminants with
      concentrations from 0.2 to 41 ng/g wet wt and from<0.04 to 37 ng/g wet wt, while
      CHLs (<0.01-1.9 ng/g wet wt), HCB (<0.004-1.0 ng/g wet wt), and HCHs (<0.02-0.4
      ng/g wet wt) were 1-2 orders of magnitude lower than the concentrations of PCBs
      and DDTs. The dominant PCBs and OCPs were PCB 153, 187, 138, and 118 and p,p'
      DDE, HCB, p,p'-DDT, and p,p'-DDD, respectively. Dietary intakes of OCs for the
      general population, males, and females were estimated as 69, 78, and 60 ng/kg
      body weight/week, respectively. Mackerel, tuna, and hairtail were the main
      contributors to the dietary intakes of OCs. Among the eight age groups
      investigated, infants <2 years had the highest dietary exposure to OCs. Hazard
      ratios of non-cancer risk of all of the OCs were less than one, while the
      lifetime cancer risks of PCBs and DDTs were all greater than unity for Korean
      populations.

PMID- 19406200
TI  - Safety assessment of heat-sterilized green tea catechin preparation: a 6-month
      repeat-dose study in rats.
AB  - Evidence suggests that the purported health benefits associated with green tea
      consumption are related to tea catechins. In the present study, potential adverse
      effects of a standardized heat-sterilized green tea catechin (GTC-H) preparation
      was investigated following gavage administration to rats at doses of 0, 120, 400,
      1200 mg/kg/day for 6 months. A decaffeinated high-dose group (1200 mg/kg/day)
      (GTC-HDC), was included for comparison. A possibly test article-related clinical
      finding of intermittent increased activity was noted in the 400 and 1200
      mg/kg/day GTC-H groups, but was not considered to be adverse. Lower body weight
      gains without any decrease in food consumption were noted in the high-dose (1200
      mg/kg/day)-treated GTC-H and GTC-HDC females. In the high-dose male GTC-H group,
      a lower total motor activity count for the 60-min session was noted prior to
      dosing at the study week 25 evaluations compared to the control group. Similar
      changes were not observed in the GTC-HDC group. Based on the results of this
      study, the no-observed-adverse-effect level (NOAEL) for GTC-H was 1200 mg/kg/day
      for males, the highest dose tested, and 400mg/kg/day for females based on reduced
      body weight gains. The NOAEL for GTC-HDC was 1200 mg/kg/day for males and could
      not be determined in females.

PMID- 19406199
TI  - Protective effects of Salvia plebeia compound homoplantaginin on hepatocyte
      injury.
AB  - Salvia plebeia R. Br is a traditional Chinese herb which has been considered as
      an inflammatory mediator used for treatment of many infectious diseases including
      hepatitis. Previously, the compound homoplantaginin was isolated in our group.
      Hence, we evaluated the protective effects of homoplantaginin on hepatocyte
      injury. Homoplantaginin displayed an antioxidant property in a cell-free system
      and showed IC(50) of reduction level of DPPH radical at 0.35 microg/ml. In human
      hepatocyte HL-7702 cells exposed to H(2)O(2), the addition of 0.1-100 microg/ml
      of homoplantaginin, which did not have a toxic effect on cell viability,
      significantly reduced lactate dehydrogenase (LDH) leakage, and increased
      glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)
      in supernatant. In vivo assay, we employed the model of Bacillus Calmette-Guerin
      (BCG)/lipopolysaccharide (LPS)-induced hepatic injury mice to evaluate efficacy
      of homoplantaginin. Homoplantaginin (25-100mg/kg) significantly reduced the
      increase in serum alanine aminotranseferase (ALT) and aspartate aminotransferase
      (AST), decreased the levels of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1 (IL-1). The same treatment also reduced the content of
      thiobarbituric acid-reactive substances (TBARS), elevated the levels of GSH, GSH
      Px and SOD in hepatic homogenate. The histopathological analysis showed that the
      grade of liver injury was ameliorated with reduction of inflammatory cells and
      necrosis of liver cells in homoplantaginin treatment mice. These results suggest
      that homoplantaginin has a protective and therapeutic effect on hepatocyte
      injury, which might be associated with its antioxidant properties.

PMID- 19406201
TI  - The subcellular localization of MEK and ERK--a novel nuclear translocation signal
      (NTS) paves a way to the nucleus.
AB  - The ERK cascade is a central signaling pathway that regulates a large number of
      intracellular processes including proliferation, differentiation, development and
      also survival or apoptosis. The induction of so many distinct and even opposing
      cellular processes raises the question as to how the signaling specificity of the
      cascade is regulated. In the past few years, subcellular localization of
      components of the ERK cascade was shown to play an important role in specificity
      determination. Here we describe the dynamic subcellular localization of Raf
      kinases, MEKs, and particularly ERKs, which translocate into the nucleus during
      many cellular processes to induce transcription. We also describe in details the
      recent identification of a novel nuclear translocation mechanism for ERKs, which
      is based on a nuclear translocation sequence (NTS) within their kinase insert
      domain (KID). Phosphorylation of this domain, mainly upon stimulation, allows
      ERKs to interact with the nuclear importing protein - importin7, which mediates
      the penetration of the interacting ERKs into the nucleus via nuclear pores.
      Interestingly, the NTS is not specific to ERKs, and seems to be a general signal
      for regulating nuclear accumulation of various proteins, including MEKs, upon
      their stimulation. Better understanding of this mechanism may clarify the role of
      the massive nuclear translocation of many regulatory proteins shortly after their
      stimulation.

PMID- 19406202
TI  - Endocrine/paracrine control of zebrafish ovarian development.
AB  - Ovarian differentiation and the processes of follicle development, oocyte
      maturation and ovulation are complex events, requiring the coordinated action of
      regulatory molecules. In zebrafish, ovarian development is initiated at 10 days
      after hatching and fish become sexually mature at 3 months. Adult zebrafish have
      asynchronous ovaries, which contain follicles of all stages of development. Eggs
      are spawned daily under proper environmental conditions in a population of
      zebrafish, with individual females spawning irregularly every 4-7 days in mixed
      sex conditions. Maximal embryo viability is achieved when sexually isolated
      females are bred in 10-day intervals [Niimi, A.J., LaHam, Q.N., 1974. Influence
      of breeding time interval on egg number, mortality, and hatching of the zebra
      fish Brachydanio verio. Can. J. Zool. 52, 515-517]. Similar to other vertebrates,
      hormones from the hypothalamus-pituitary-gonadal axis play important roles in
      regulating follicle development. Follicle stimulating hormone (FSH) stimulates
      estradiol production, which in turn, promotes viteollogenesis. Luteinizing
      hormone (LH) stimulates the production of 17,20beta-dihydroxy-4-pregnen-3-one
      (17,20betaP) or maturation inducing hormone (MIH) which acts through membrane
      progestin receptors to activate maturation promoting factor, leading to oocyte
      maturation. Recent studies in zebrafish have also provided novel insights into
      the functions of ovary-derived growth factors in follicle development and oocyte
      maturation. The present review summarizes the current knowledge on how endocrine
      and paracrine factors regulate ovarian development in zebrafish. Special emphasis
      is placed on how follicle development and oocyte maturation in adult females is
      regulated by gonadotropins, ovarian steroids and growth factors produced by the
      ovary.

PMID- 19406203
TI  - Micro-RNA abundance and stability in human brain: specific alterations in
      Alzheimer's disease temporal lobe neocortex.
AB  - Micro-RNA (miRNA) mediated regulation of messenger RNA (mRNA) complexity in the
      central nervous system (CNS) is emerging as a critical factor in the control of
      CNS-specific gene expression during development, plasticity, aging and disease.
      In these studies, miRNA array and Northern blot based tracking of specific miRNA
      abundances and decay kinetics in human neural (HN) cells in primary culture and
      in short post-mortem interval (PMI, approximately 1h) human brain tissues showed
      a limited stability and relatively short half-life ( approximately 1-3.5h) for
      specific brain-enriched miRNAs. In short PMI Alzheimer's disease (AD)-affected
      temporal lobe neocortex, miRNA-9, miRNA-125b and miRNA-146a were found to be
      significantly up-regulated, an effect that was not seen in several related
      neurological disorders. The results suggest (a) that unless specifically
      stabilized, certain brain-enriched miRNAs represent a rapidly executed signaling
      system employing highly transient effectors of CNS gene expression, and (b) that
      in AD temporal lobe neocortex specific brain miRNAs are significantly up
      regulated in abundance and strongly correlate with the presence of AD-type
      neuropatholgical change.

PMID- 19406204
TI  - Role of TRPV1 in high-threshold rat colonic splanchnic afferents is revealed by
      inflammation.
AB  - The vanilloid-1 receptor TRPV1 is known to play a role in extrinsic
      gastrointestinal afferent function. We investigated the role of TRPV1 in
      mechanosensitivity in afferents from normal and inflamed tissue. Colonic
      mechanosensitivity was determined in an in vitro rat colon preparation by
      recording from attached splanchnic nerves. Recordings were made from
      serosal/mesenteric afferents responding only at high thresholds to graded
      mechanical stimulation with von Frey probes. Colonic inflammation was induced by
      adding 5% dextran sulphate sodium (DSS) to the drinking water for 5 days, and was
      confirmed by histopathology. The selective TRPV1 antagonist, SB-750364 (10(-8) to
      10(-6)M), was tested on mechanosensory stimulus response functions of afferents
      from normal and inflamed preparations (N=7 each). Mechanosensory responses had
      thresholds of 1-2g, and maximal responses were observed at 12 g. The stimulus
      response function was not affected by DSS-induced colitis. SB-750364 had no
      effect on stimulus response functions in normal preparations, but reduced (up to
      60%) in a concentration-dependent manner those in inflammation (2-way ANOVA,
      p<0.05). Moreover, in inflamed tissue, spontaneous afferent activity showed a
      dose-dependent trend toward reduction with SB-750364. We conclude that
      mechanosensitivity of high-threshold serosal colonic splanchnic afferents to
      graded stimuli is unaffected during DSS colitis. However, there is a positive
      influence of TRPV1 in mechanosensitivity in inflammation, suggesting up
      regulation of excitatory TRPV1-mediated mechanisms.

PMID- 19406205
TI  - Using chemical approaches to study selenoproteins-focus on thioredoxin
      reductases.
AB  - The study of selenocysteine-containing proteins is difficult due to the problems
      associated with the heterologous production of these proteins. These problems are
      due to the intricate recoding mechanism used by cells to translate the UGA codon
      as a sense codon for selenocysteine. The process is further complicated by the
      fact that eukaryotes and prokaryotes have different UGA recoding machineries.
      This review focuses on chemical approaches to produce selenoproteins and study
      the mechanism of selenoenzymes. The use of intein-mediated peptide ligation is
      discussed with respect to the production of the mammalian selenoenzymes
      thioredoxin reductase and selenoprotein R, also known as methionine sulfoxide
      reductase B1. New methods for removing protecting groups from selenocysteine post
      synthesis and methods for selenosulfide/diselenide formation are also reviewed.
      Chemical approaches have also been used to study the enzymatic mechanism of
      thioredoxin reductase. The approach divides the enzyme into two modules, a large
      protein module lacking selenocysteine and a small, synthetic selenocysteine
      containing peptide. Study of this semisynthetic enzyme has revealed three
      distinct enzymatic pathways that depend on the properties of the substrate. The
      enzyme utilizes a macromolecular mechanism for protein substrates, a second
      mechanism for small molecule substrates and a third pathway for selenium
      containing substrates such as selenocystine.

PMID- 19406206
TI  - Metabolism of selenium compounds catalyzed by the mammalian selenoprotein
      thioredoxin reductase.
AB  - The mammalian thioredoxin reductases (TrxR) are selenoproteins with a catalytic
      selenocysteine residue which in the oxidized enzyme forms a selenenylsulfide and
      in the reduced enzyme is present as a selenolthiol. Selenium compounds such as
      selenite, selenodiglutathione and selenocystine are substrates for the enzyme
      with low K(m)-values and the enzyme is implicated in reductive assimilation of
      selenium by generating selenide for selenoprotein synthesis. Redox cycling of
      reduced metabolites of these selenium compounds including selenide with oxygen
      via TrxR and reduced thioredoxin (Trx) will oxidize NADPH and produce reactive
      oxygen species inducing cell death at high concentrations explaining selenite
      toxicity. There is no free pool of selenocysteine since this would be toxic in an
      oxygen environment by redox cycling via thioredoxin systems. The importance of
      selenium compounds and TrxR in cancer and cardiovascular diseases both for
      prevention and treatment is discussed. A selenazol drug like ebselen is a direct
      substrate for mammalian TrxR and dithiol Trx and ebselen selenol is readily
      reoxidized by hydrogen peroxide and lipid hydroperoxides, acting as an anti
      oxidant and anti-inflammatory drug.

PMID- 19406208
TI  - The multiple personality disorder phenotype(s) of circulating endothelial cells
      in cancer.
AB  - Circulating endothelial cells (CECs) and circulating endothelial progenitors
      (CEPs) are currently being investigated in a variety of diseases as markers of
      vascular turnover or damage and, also in the case of CEPs, vasculogenesis. CEPs
      appear to have a "catalytic" role in different steps of cancer progression and
      recurrence after therapy, and there are preclinical and clinical data suggesting
      that CEC enumeration might be useful to select and stratify patients who are
      candidates for anti-angiogenic treatments. In some types of cancer, CECs and CEPs
      might be one of the possible hidden identities of cancer stem cells. The
      definition of CEC and CEP phenotype and the standardization of CEC and CEP
      enumeration strategies are highly desirable goals in order to exploit these cells
      as reliable biomarkers in oncology clinical trials.

PMID- 19406207
TI  - Functions and evolution of selenoprotein methionine sulfoxide reductases.
AB  - Methionine sulfoxide reductases (Msrs) are thiol-dependent enzymes which catalyze
      conversion of methionine sulfoxide to methionine. Three Msr families, MsrA, MsrB,
      and fRMsr, are known. MsrA and MsrB are responsible for the reduction of
      methionine-S-sulfoxide and methionine-R-sulfoxide residues in proteins,
      respectively, whereas fRMsr reduces free methionine-R-sulfoxide. Besides acting
      on proteins, MsrA can additionally reduce free methionine-S-sulfoxide. Some MsrAs
      and MsrBs evolved to utilize catalytic selenocysteine. This includes MsrB1, which
      is a major MsrB in cytosol and nucleus in mammalian cells. Specialized machinery
      is used for insertion of selenocysteine into MsrB1 and other selenoproteins at in
      frame UGA codons. Selenocysteine offers catalytic advantage to the protein repair
      function of Msrs, but also makes these proteins dependent on the supply of
      selenium and requires adjustments in their strategies for regeneration of active
      enzymes. Msrs have roles in protecting cellular proteins from oxidative stress
      and through this function they may regulate lifespan in several model organisms.

PMID- 19406211
TI  - Altered synchrony and connectivity in neuronal networks expressing an autism
      related mutation of neuroligin 3.
AB  - The neuroligin (NL) gene family codes for brain specific cell adhesion molecules
      that play an important role in synaptic connectivity. Recent studies have
      identified NL mutations linked to patients with autism spectrum disorders (ASD).
      Cognitive deficits seen in autistic patients are hypothesized to arise from
      altered synchronicity both within and between brain regions. Here we show how the
      expression of autism-associated neuroligin mutation R471C-NL3 affects synchrony
      in dissociated cultures of rat hippocampal neurons. Spontaneous network activity
      patterns of cultures expressing wild type and mutant NL3 were measured by optical
      techniques. Firing events were quantified and compared by cross-correlation
      analysis. Our results suggest that NL3 overexpression enhances synchrony of
      spontaneous activity patterns, however, this ability is reduced with the R471C
      NL3 mutation. We investigated the structural basis of this phenomenon using
      fractal dimension analysis to characterize the arrangement of axon trajectories.
      R471C-NL3 cultures were associated with lower fractal dimensions and higher
      lacunarity values, indicating a decrease in the complexity of axonal
      architecture. Transfection of R471C-NL3 into a subpopulation of cells in a
      network resulted in neuronal degeneration. This degeneration likely affected the
      inhibitory population of neurons, as there were half as many (P<0.01, n=12)
      glutamate decarboxylase (GAD) 65 expressing cells in R471C-NL3 cultures compared
      to wild type NL3 and control cultures. Electrophysiological recordings showed a
      reduction of inhibitory activity in networks carrying the mutation in comparison
      to networks overexpressing wild-type NL3. Together, these data support the
      hypothesis that the autism-associated NL3 mutation affects information processing
      in neuronal networks by altering network architecture and synchrony.

PMID- 19406209
TI  - Translocations in epithelial cancers.
AB  - Genomic translocations leading to the expression of chimeric transcripts
      characterize several hematologic, mesenchymal and epithelial malignancies. While
      several gene fusions have been linked to essential molecular events in
      hematologic malignancies, the identification and characterization of recurrent
      chimeric transcripts in epithelial cancers has been limited. However, the recent
      discovery of the recurrent gene fusions in prostate cancer has sparked a
      revitalization of the quest to identify novel rearrangements in epithelial
      malignancies. Here, the molecular mechanisms of gene fusions that drive several
      epithelial cancers and the recent technological advances that increase the speed
      and reliability of recurrent gene fusion discovery are explored.

PMID- 19406212
TI  - Mechanisms that limit the light stimulus frequency following through the DL-2
      amino-4-phosphonobutyric acid sensitive and insensitive rod Off-pathways.
AB  - In the retina, rod signal pathways process scotopic visual information. Light
      decrements are mediated by two distinct groups of rod pathways in the dark
      adapted retina that can be differentiated on the basis of their sensitivity to
      the glutamate agonist dl-2-amino-4-phosphonobutyric acid (APB). We have found
      that the APB sensitive and insensitive rod Off-pathways signal different light
      decrement information: the APB sensitive rod Off-pathway conveys slow and low
      frequency light signals, whereas the APB insensitive rod Off-pathways mediate
      fast and high frequency light signals [Wang GY (2006) Unique functional
      properties of the APB sensitive and insensitive rod pathways signaling light
      decrements in mouse retinal ganglion cells. Vis Neurosci 23:127-135]. However,
      the mechanisms which limit the frequency following through the APB sensitive and
      insensitive rod Off-pathways remain unknown. In the current study, whole-cell
      patch-clamp recordings were made from ganglion cells in dark and light adapted
      mouse retina to identify the mechanisms that limit the frequency following
      through the APB sensitive and insensitive rod Off-pathways. The results showed
      that the sites from AII amacrine cells to Off cone bipolar cells are the major
      mechanisms that limit the frequency following through the APB sensitive rod Off
      pathway. In the APB insensitive rod Off-pathways, rods themselves limited the
      frequency following through these pathways. Moreover, ganglion cells were able to
      follow higher frequencies under photopic conditions than under scotopic
      conditions. The Off responses followed lower frequencies than On responses under
      photopic conditions. This finding was observed in cells that yielded On or Off
      responses only as well as in On-Off cells.

PMID- 19406214
TI  - Motor control over the phantom limb in above-elbow amputees and its relationship
      with phantom limb pain.
AB  - Recent evidence shows that the primary motor cortex continues to send motor
      commands when amputees execute phantom movements. These commands are retargeted
      toward the remaining stump muscles as a result of motor system reorganization. As
      amputation-induced reorganization in the primary motor cortex has been associated
      with phantom limb pain we hypothesized that the motor control of the phantom limb
      would differ between amputees with and without phantom limb pain. Eight above
      elbow amputees with or without pain were included in the study. They were asked
      to produce cyclic movements with their phantom limb (hand, wrist, and elbow
      movements) while simultaneously reproducing the same movement with the intact
      limb. The time needed to complete a movement cycle and its amplitude were derived
      from the kinematics of the intact limb. Electromyographic (EMG) activity from
      different stump muscles and from the homologous muscles on the intact side was
      recorded. Different EMG patterns were recorded in the stump muscles depending on
      the movement produced, showing that different phantom movements are associated
      with distinct motor commands. Phantom limb pain was associated with some aspects
      of phantom limb motor control. The time needed to complete a full cycle of a
      phantom movement was systematically shorter in subjects without phantom limb
      pain. Also, the amount of EMG modulation recorded in a stump muscle during a
      phantom hand movement was positively correlated with the intensity of phantom
      limb pain. Since phantom hand movement-related EMG patterns in above-elbow stump
      muscles can be considered as a marker of motor system reorganization, this result
      indirectly supports the hypothesis that amputation-induced plasticity is
      associated with phantom limb pain severity. The discordance between the
      (amputated) hand motor command and the feedback from above-elbow muscles might
      partially explain why subjects exhibiting large EMG modulation during phantom
      hand movement have more phantom limb pain.

PMID- 19406215
TI  - Tyrosine hydroxylase-positive amacrine interneurons in the mouse retina are
      resistant against the application of various parkinsonian toxins.
AB  - Toxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6
      hydroxydopamine (6-OHDA), or rotenone have been used to induce degeneration of
      dopaminergic (DA) neurons in the nigrostriatal pathway and to reproduce
      pathological characteristics of Parkinson's disease (PD). DA neurons are also
      present in the retina, and visual impairments in PD patients have been reported.
      We examined the vulnerability of TH-positive (TH(+)) amacrine interneurons in the
      retina against MPTP, 6-OHDA, or rotenone-induced cell death. We intraperitoneally
      (i.p.) injected mice with MPTP, which induced degeneration of DA neurons in the
      midbrain. However, no death of TH(+) amacrine cells was detectable in the same
      mice. HPLC analysis revealed a 9 times lower level of the toxic metabolite of
      MPTP, MPP(+), in the eye compared with the striatum. Another membrane-permeable
      compound (Tat-Hsp70) could be delivered into the retina after i.p. application,
      suggesting that the blood-retina barrier (BRB) could be overcome after systemic
      application. Possible reason for the survival of retinal amacrine cells after
      systemic MPTP application was a less efficient conversion into toxic MPP(+) in
      the retina or a general higher resistance against toxic insults of retinal DA
      neurons compared with DA neurons in the substantia nigra pars compacta (SNpc).
      Therefore, we directly injected high doses of MPP(+), 6-OHDA, or rotenone into
      the eye. No loss of TH(+) amacrine cells in the retina was observed, suggesting
      different properties and less vulnerability of amacrine neurons compared with DA
      neurons in the midbrain.

PMID- 19406213
TI  - Molecular interactions of the plasma membrane calcium ATPase 2 at pre- and post
      synaptic sites in rat cerebellum.
AB  - The plasma membrane calcium extrusion mechanism, PMCA (plasma membrane calcium
      ATPase) isoform 2 is richly expressed in the brain and particularly the
      cerebellum. Whilst PMCA2 is known to interact with a variety of proteins to
      participate in important signalling events [Strehler EE, Filoteo AG, Penniston
      JT, Caride AJ (2007) Plasma-membrane Ca(2+) pumps: structural diversity as the
      basis for functional versatility. Biochem Soc Trans 35 (Pt 5):919-922], its
      molecular interactions in brain synapse tissue are not well understood. An
      initial proteomics screen and a biochemical fractionation approach identified
      PMCA2 and potential partners at both pre- and post-synaptic sites in synapse
      enriched brain tissue from rat. Reciprocal immunoprecipitation and GST pull-down
      approaches confirmed that PMCA2 interacts with the post-synaptic proteins PSD95
      and the NMDA glutamate receptor subunits NR1 and NR2a, via its C-terminal PDZ
      (PSD95/Dlg/ZO-1) binding domain. Since PSD95 is a well-known partner for the NMDA
      receptor this raises the exciting possibility that all three interactions occur
      within the same post-synaptic signalling complex. At the pre-synapse, where PMCA2
      was present in the pre-synapse web, reciprocal immunoprecipitation and GST pull
      down approaches identified the pre-synaptic membrane protein syntaxin-1A, a
      member of the SNARE complex, as a potential partner for PMCA2. Both PSD95-PMCA2
      and syntaxin-1A-PMCA2 interactions were also detected in the molecular and
      granule cell layers of rat cerebellar sagittal slices by immunohistochemistry.
      These specific molecular interactions at cerebellar synapses may allow PMCA2 to
      closely control local calcium dynamics as part of pre- and post-synaptic
      signalling complexes.

PMID- 19406210
TI  - Genomic and proteomic biomarkers for cancer: a multitude of opportunities.
AB  - Biomarkers are molecular indicators of a biological status, and as biochemical
      species can be assayed to evaluate the presence of cancer and therapeutic
      interventions. Through a variety of mechanisms cancer cells provide the biomarker
      material for their own detection. Biomarkers may be detectable in the blood,
      other body fluids, or tissues. The expectation is that the level of an
      informative biomarker is related to the specific type of disease present in the
      body. Biomarkers have potential both as diagnostic indicators and monitors of the
      effectiveness of clinical interventions. Biomarkers are also able to stratify
      cancer patients to the most appropriate treatment. Effective biomarkers for the
      early detection of cancer should provide a patient with a better outcome which in
      turn will translate into more efficient delivery of healthcare. Technologies for
      the early detection of cancer have resulted in reductions in disease-associated
      mortalities from cancers that are otherwise deadly if allowed to progress. Such
      screening technologies have proven that early detection will decrease the
      morbidity and mortality from cancer. An emerging theme in biomarker research is
      the expectation that panels of biomarker analytes rather than single markers will
      be needed to have sufficient sensitivity and specificity for the presymptomatic
      detection of cancer. Biomarkers may provide prognostic information of disease
      enabling interventions using targeted therapeutic agents as well as course
      corrections in cancer treatment. Novel genomic, proteomic and metabolomic
      technologies are being used to discover and validate tumor biomarkers
      individually and in panels.

PMID- 19406216
TI  - Post-ischemic hypothermia for 24h in P7 rats rescues hippocampal neuron:
      association with decreased astrocyte activation and inflammatory cytokine
      expression.
AB  - Hypothermia is an effective method for reducing the neuronal damage induced by
      hypoxia-ischemia (HI) but the underlying mechanism remains unclear. To
      investigate the effects of post-HI hypothermia on the developing brain, 7-day-old
      rats were subjected to left carotid artery ligation followed by 8% oxygen for 2h.
      They were divided into a hypothermia group (rectal temperature 32-33 degrees C
      for 24h) and a normothermia group (36-37 degrees C for 24h) immediately after
      hypoxia-ischemia. Animals were sacrificed at 12, 24 and 72 h for gene analysis
      and 0, 1, 3 and 7 days for protein analysis after HI. There was a significant
      decrease in infarct volume in the hypothermia group at 7 days after HI compared
      with that in the normothermia group. The hypothermia group had more neuronal
      nuclei (NeuN) positive neurons and lower levels of glial fibrillary acidic
      protein (GFAP) mRNA and immunoreactivity in the hippocampus CA1 region than the
      normothermia group. Real-time PCR showed no significant difference in glial cell
      line-derived neurotrophic factor (GDNF) mRNA expression in the hippocampus in the
      two groups at various time points after HI. However, GDNF protein level was
      significantly increased in the hypothermia group. On the other hand, mRNA and
      protein levels of the inflammatory cytokines tumor necrosis factor alpha (TNF
      alpha) and interleukin-6 (IL-6) were dramatically decreased in the hypothermia
      compared with the normothermia group. The present findings highlight an apparent
      association between inhibition of hippocampal neuron loss by hypothermia and
      decreased astrocytosis and inflammatory cytokine release after hypoxia-ischemia
      in the developing brain.

PMID- 19406217
TI  - Inhibition of mitochondrial respiratory chain in the brain of rats after hepatic
      failure induced by carbon tetrachloride is reversed by antioxidants.
AB  - Hepatic encephalopathy is an important cause of morbidity and mortality in
      patients with severe hepatic failure. This disease is clinically characterized by
      a large variety of symptoms including motor symptoms, cognitive deficits, as well
      as changes in the level of alertness up to hepatic coma. Carbon tetrachloride is
      frequently used in animals to produce an experimental model to study the
      mechanisms involved in the progression of hepatic disease and the impact of
      various drugs on this progression. The brain is highly dependent on ATP and most
      cell energy is obtained through oxidative phosphorylation, a process requiring
      the action of various respiratory enzyme complexes located in a special structure
      of the inner mitochondrial membrane. In this context, we evaluated the activities
      of mitochondrial respiratory chain complexes in the brain of rats submitted to
      acute administration of carbon tetrachloride and treated with NAC and DFX alone
      or in combination. Our results showed that complexes I, II and IV were inhibited
      after carbon tetrachloride administration and that NAC and DFX alone or in
      combination were able to prevent the inhibition of these enzymes. On the other
      hand, complex III was not affected. The participation of oxidative stress has
      been postulated in the hepatic encephalopathy and it is well known that the
      electron transport chain itself is vulnerable to damage by this species. Based on
      our findings, we suggest that oxidative stress may be involved in the inhibition
      of complexes from mitochondrial respiratory chain.

PMID- 19406218
TI  - Transcriptomic response of Argopecten purpuratus post-larvae to copper exposure
      under experimental conditions.
AB  - Few studies have described the molecular response of mollusk larvae to heavy
      metal exposure. We investigated the response of Chilean scallop Argopecten
      purpuratus post-larvae to copper exposure under experimental conditions. Post
      larvae were maintained with and without copper stress in tanks containing netlon
      collectors with biofilms that were formed by the bacterium Halomonas sp. and the
      diatom Amphora sp., known to increase larval settlement. We focused on the
      analysis of the differential expression patterns of genes associated with copper
      response. A suppression subtractive hybridization method was used to identify
      copper-specific up- and down-regulated genes in the post-larvae following 4 days
      and 8 days exposure to 2.5 and 10 microg/l Cu(+2). This method revealed 145
      different sequences corresponding to 10 major physiological functions. The
      expression of 15 potentially regulated genes was analyzed by real-time PCR in
      post-larvae at different sampling times during the copper stress. The genes
      chosen were alpha tubulin, elongation factor 1-alpha (EF1A), tributylin binding
      protein type 1 (TBT), NADH dehydrogenase subunit 2 (NADH2), cavortin, glutathione
      peroxidase (GPx), ferritin, heat shock protein 70 (HSP70), Pam highwire rpm1
      (Phr1), insulin-like growth factor 1 (IGF1), cellulase, and ribosomal proteins:
      L18, L44, S3a and S15. This study contributes to the characterization of
      potential genetic markers that could be used in future environmental monitoring
      and to explore new mechanisms of stress tolerance in marine mollusk species,
      especially in early stages of development.

PMID- 19406219
TI  - Structure of the amphioxus nebulin gene and evolution of the nebulin family
      genes.
AB  - Nebulin family genes are believed to have diverged from a single gene during the
      evolution of vertebrates. We determined the structure of the amphioxus nebulin
      gene and showed that in addition to the features of the human nebulin gene, this
      gene had a LIM domain, secondary super repeats and a giant exon with 98 nebulin
      repeats containing unique sequences. A transcript of this gene amplified by
      reverse transcriptase-polymerase chain reaction had a LIM domain, three nebulin
      repeats and an SH3 domain. This transcript was similar to an isoform of human
      nebulette (Lasp-2). Phylogenetic analysis using the LIM and SH3 domains of the
      nebulin family proteins showed that amphioxus nebulin is located outside the
      vertebrate nebulin family group in the phylogenetic tree. These results indicated
      that the amphioxus nebulin gene had a unified structure among nebulin, nebulette,
      lasp-1 and N-RAP of vertebrates, and that these nebulin family genes diverged
      from the amphioxus nebulin gene during the course of vertebrate evolution.

PMID- 19406220
TI  - Acute renal failure enhances the antidotal activity of pralidoxime towards
      paraoxon-induced respiratory toxicity.
AB  - We recently showed in a rat model of dichromate-induced acute renal failure (ARF)
      that the elimination but not the distribution of pralidoxime was altered
      resulting in sustained plasma pralidoxime concentrations. The aim of this study
      was to compare the efficiency of pralidoxime in normal and acute renal failure
      rats against paraoxon-induced respiratory toxicity. Ventilation at rest was
      assessed using whole-body plethysmography after subcutaneous administration of
      either saline or paraoxon (50% of the LD(50)), in the control and ARF rats.
      Thirty minutes after administration of paraoxon, either saline or 50mg/kg of
      pralidoxime was administered intramuscularly. ARF had no significant effects on
      the ventilation at rest. The effects of paraoxon on respiration were not
      significantly different in the control and ARF group. Paraoxon increased the
      total time (T(TOT)), expiratory time (T(E)) and tidal volume (V(T)), and
      decreased the respiratory frequency (f). In paraoxon-poisoned rats with normal
      renal function, pralidoxime had a significant but transient effect regarding the
      T(TOT) and V(T) (p<0.05). In the ARF group, the same dose of pralidoxime
      significantly decreased the T(TOT), T(E), and V(T) and increased f during 90 min
      (p<0.01). In conclusion, pralidoxime had partial and transient effects towards
      paraoxon-induced respiratory toxicity in control rats; and a complete and
      sustained correction in ARF rats.

PMID- 19406221
TI  - Trivalent chromium activates Rac-1 and Src and induces switch in the cell death
      mode in human dermal fibroblasts.
AB  - In this study we examined interactions between human dermal fibroblasts and
      chromium acetate hydroxide originating from environmental waste sediments. We
      show that initially exposure of fibroblasts to Cr (III) induced membrane
      dependent signaling including activation of Rac1 GTPase, Src and apoptosis signal
      regulating kinase 1 (ASK-1) kinases leading to increased activities of p38 and
      particularly Jun N-terminal kinase (JNK) and subsequent activation of caspase-3.
      At later treatment intervals (48-96 h), caspase-3 activity became suppressed and
      markedly increased lactate dehydrogenase (LDH) release was observed. Further
      experiments demonstrated that LDH release occurred in the presence of increased
      oxidative stress, extensive DNA damage, overactivation of poly(ADP
      ribose)polymerase-1 (PARP-1) and depletion of ATP. Using specific inhibitors it
      was demonstrated that oxidative stress along with PARP-1 activity are responsible
      for cell death mode switch and upon their inhibition caspase-3 activity could be
      restored. In conclusion, Cr (III) seems to induce a biphasic response in dermal
      fibroblasts, with initial apoptosis switched to necrosis via increased DNA damage
      and resulting PARP-1 activity.

PMID- 19406223
TI  - Identification of epigallocatechin-3-gallate in green tea polyphenols as a potent
      inducer of p53-dependent apoptosis in the human lung cancer cell line A549.
AB  - The effects of green tea polyphenols on cultured cancer cells have been well
      characterized, especially the effects of epigallocatechin-3-gallate (EGCg), since
      EGCg suppresses oncogenic signaling pathways and induces cell cycle arrest or
      apoptosis by regulating cell cycle-associated proteins. In the present study, we
      attempted to identify signaling pathways or target molecules regulated by each of
      or a mixture of green tea polyphenols, including epicatechin (EC), epicatechin-3
      gallate (ECg), epigallocatechin (EGC), and EGCg, in the human lung cancer cell
      line A549. ECg, EGC, and a catechin mixture, in addition to EGCg, significantly
      decreased cell viability. In contrast, caspase 3/7 activity, an apoptosis
      indicator, was specifically induced by EGCg. By conducting a series of luciferase
      based reporter assays, we revealed that the catechin mixture only up-regulates
      the p53 reporter. EGCg was a more potent inducer of p53-dependent transcription,
      and this induction was further supported by the induced level of p53 protein. RNA
      interference (RNAi)-mediated p53 knockdown completely abolished EGCg-induced
      apoptosis. Finally, a proteome and western blot analysis using approximately 70
      different antibodies failed to detect up-regulated proteins in catechin mixture
      treated A549 cells. Taken together, these results indicate that EGCg, among
      several green tea polyphenols, is a potent apoptosis inducer that functions
      exclusively through a p53-dependent pathway in A549 cells.

PMID- 19406222
TI  - Carbon dioxide effects on olfactory functioning: behavioral, histological and
      immunohistochemical measurements.
AB  - Most studies on toxic inhalation focus on solvent effects and few have dealt with
      gases on olfactory functioning. Among gases, the effects of carbon dioxide on
      general physiology have been well investigated contrary to the impact on
      olfactory neuroepithelium. Thus, this work was designed to evaluate in mice the
      possible effects of 3% CO(2) in two exposure periods: a 5h/day and a 12h/day
      conditions. Behavioral, histological and immunohistochemical observations were
      conducted every 2 weeks, i.e. before (W0), during (W2, W4) and after exposure
      (W6, W8). Firstly, behavioral evaluations of odor sensitivity showed differences
      in relation to the odor tested, i.e. no effect with congener urine odor and a
      reinforcement of 2,4,5-trimethythiazoline (TMT) (predator odor) repulsion.
      Secondly, histological evaluations showed a similar evolution of the epithelium
      thickness, i.e. a decrease along the exposure as well as during the post-exposure
      period and an increase of cell number (whatever the phenotype) although the
      kinetic appeared different in both experimental conditions. Thirdly,
      immunohistochemical quantification of olfactory marker protein (OMP)- and
      proliferating cell nuclear antigen (PCNA)-positive cells revealed that the number
      of mature olfactory neurons increased at the early beginning of exposure period
      in both conditions. While a decrease was observed in the following weeks (W4-W8)
      for the 12h/day condition, a stable amount of OMP-positive cells was maintained
      in the 5h/day condition. In contrast, the number of PCNA-positive cells followed
      a similar evolution, i.e. a constant decrease along the experiment. These
      findings indicate that the effects of CO(2) inhalation exposure are selectively
      dose-dependent.

PMID- 19406224
TI  - Global transcriptional characterization of a mouse pulmonary epithelial cell line
      for use in genetic toxicology.
AB  - Prior to its application for in vitro toxicological assays, thorough
      characterization of a cell line is essential. The present study uses global
      transcriptional profiling to characterize a lung epithelial cell line (FE1)
      derived from MutaMouse [White, P.A., Douglas, G.R., Gingerich, J., Parfett, C.,
      Shwed, P., Seligy, V., Soper, L., Berndt, L., Bayley, J., Wagner, S., Pound, K.,
      Blakey, D., 2003. Development and characterization of a stable epithelial cell
      line from Muta Mouse lung. Environmental and Molecular Mutagenesis 42, 166-184].
      Results presented here demonstrate the origin of the FE1 lung cell line as
      epithelial, presenting both type I and type II alveolar phenotype. An assessment
      of toxicologically-relevant genes, including those involved in the response to
      stress and stimuli, DNA repair, cellular metabolism, and programmed cell death,
      revealed changes in expression of 22-27% of genes in one or more culture type
      (proliferating and static FE1 cultures, primary epithelial cultures) compared
      with whole lung isolates. Gene expression analysis at 4 and 24h following
      benzo(a)pyrene exposure revealed the induction of cyp1a1, cyp1a2, and cyp1b1 in
      FE1 cells and lung isolates. The use of DNA microarrays for gene expression
      profiling allows an improved understanding of global, coordinated cellular events
      arising in cells under different physiological conditions. Taken together, these
      data indicate that the FE1 cell line is derived from a cell type relevant to
      toxic responses in vivo, and shows some similarity in response to chemical insult
      as the original tissue.

PMID- 19406225
TI  - In silico detection and characteristics of novel microRNA genes in the Equus
      caballus genome using an integrated ab initio and comparative genomic approach.
AB  - The importance of microRNAs at the post-transcriptional regulation level has
      recently been recognized in both animals and plants. We used the simple but
      effective sequential method of first Blasting known animal miRNAs against the
      horse genome and then using the located candidates to search for novel miRNAs by
      RNA folding method in the vicinity (+ -500 bp) of the candidates. Here, a total
      of 407 novel horse miRNA genes including 354 mature miRNAs were identified, of
      these, 75 miRNAs were grouped into 32 families based on seed sequence identity.
      MiRNA genes tend to be present as clusters in some chromosomes, and 146 miRNA
      genes accounted for 36% of the total were observed as part of polycistronic
      transcripts. Detailed analysis of sequence characteristics in novel horse and all
      previous known animal miRNAs were carried out. Our study will provide a reference
      point for further study on miRNAs identification in animals and improve the
      understanding of genome in horse.

PMID- 19406226
TI  - Abnormalities in serum chemokine levels in euthymic patients with bipolar
      disorder.
AB  - The pathophysiology of bipolar disorder (BD) includes, among other processes,
      changes in the neuroplasticity and regulation of apoptosis, which could
      potentially be influenced by inflammatory mediators such as chemokines. The
      objectives of this study were to investigate serum chemokine levels in patients
      with BD and to compare results with those obtained with healthy subjects. Here,
      serum chemokine levels of 30 euthymic patients with BD type I and 30 healthy
      volunteers were investigated and compared. The chemokines assessed were CCL2,
      CCL3, CCL8, CCL 9, CCL10, CCL11, and CCL24. Patients with BD showed significant
      differences in chemokine levels when compared with healthy subjects. While serum
      levels of CXCL10 were increased (p=.018), CCL24 levels were lower in bipolar
      patients (p=.025) when compared with controls. There was no statistical
      difference in the serum levels of CCL2, CCL3, CCL24, CXCL9, and CXCL11 between
      patients and controls. The presence of chemokine abnormalities in patients with
      BD during euthymia suggests that these inflammatory mediators should be further
      investigated with regard to their potential role as longstanding markers of the
      disorder.

PMID- 19406228
TI  - Temperature and solvent effects in the solubility of some pharmaceutical
      compounds: Measurements and modeling.
AB  - In this work, pure solvent solubilities of drugs, such as paracetamol,
      allopurinol, furosemide and budesonide, measured in the temperature range between
      298.2-315.2K are presented. The solvents under study were water, ethanol,
      acetone, ethyl acetate, carbon tetrachloride and n-hexane. Measurements were
      performed using the shake-flask method for generating the saturated solutions
      followed by compositional analysis by HPLC. Previous literature values on the
      solubilities of paracetamol were used to assess the experimental methodology
      employed in this work. No literature data was found for any of the other drugs
      studied in this assay. Melting properties of the pure drugs were also determined
      by differential scanning calorimetry (DSC) to provide a broader knowledge about
      the solubilization process and also for modeling purposes. The solubility data as
      a function of temperature were used to determine the thermodynamic properties of
      dissolution like, Gibbs energy, enthalpy and entropy. Theoretical work was
      essentially focused on the evaluation of the Nonrandom Two-Liquid Segment
      Activity Coefficient (NRTL-SAC) model, which has been referred as a simple and
      practical thermodynamic framework for drug solubility estimation. A satisfactory
      agreement was found between experimental and calculated values: the absolute
      average deviation was 68% for the correlation in the organic solvents and 38% for
      the prediction in water, where the best results in prediction could be related to
      the selected solvents.

PMID- 19406227
TI  - Zebrafish embryos as models for embryotoxic and teratological effects of
      chemicals.
AB  - The experimental virtues of the zebrafish embryo such as small size, development
      outside of the mother, cheap maintenance of the adult made the zebrafish an
      excellent model for phenotypic genetic and more recently also chemical screens.
      The availability of a genome sequence and several thousand mutants and transgenic
      lines together with gene arrays and a broad spectrum of techniques to manipulate
      gene functions add further to the experimental strength of this model. Pioneering
      studies suggest that chemicals can have in many cases very similar toxicological
      and teratological effects in zebrafish embryos and humans. In certain areas such
      as cardiotoxicity, the zebrafish appears to outplay the traditional rodent models
      of toxicity testing. Several pilot projects used zebrafish embryos to identify
      new chemical entities with specific biological functions. In combination with the
      establishment of transgenic sensor lines and the further development of existing
      and new automated imaging systems, the zebrafish embryos could therefore be used
      as cost-effective and ethically acceptable animal models for drug screening as
      well as toxicity testing.

PMID- 19406229
TI  - Influence of structural variations on drug release from lipid/polyethylene glycol
      matrices.
AB  - Different combinations of monoacid triglycerides and polyethylene glycol powders
      of different molecular weights were successfully extruded below their melting
      temperatures as a basis for oral dosage forms. The incorporated polyethylene
      glycols exhibiting different mean molecular weights were compared with respect to
      their effect on the dissolution rate for a model drug, and a mean molecular
      weight of 10,000 resulted in the most advantageous characteristics (fastest
      dissolution). Triglycerides with different fatty acid chain lengths provided
      additional options for the extrusion temperature which is beneficial for
      temperature sensitive active pharmaceutical ingredients. To obtain stable
      extrudates with desirable and reproducible dissolution characteristics a good
      understanding of the underlying processes during processing and storage is
      mandatory.

PMID- 19406230
TI  - Artificial neural networks modelling the prednisolone nanoprecipitation in
      microfluidic reactors.
AB  - This study employs artificial neural networks (ANNs) to create a model to
      identify relationships between variables affecting drug nanoprecipitation using
      microfluidic reactors. The input variables examined were saturation levels of
      prednisolone, solvent and antisolvent flow rates, microreactor inlet angles and
      internal diameters, while particle size was the single output. ANNs software was
      used to analyse a set of data obtained by random selection of the variables. The
      developed model was then assessed using a separate set of validation data and
      provided good agreement with the observed results. The antisolvent flow rate was
      found to have the dominant role on determining final particle size.

PMID- 19406231
TI  - Preparation and characterization of solid lipid nanoparticles loaded with
      doxorubicin.
AB  - Solid lipid nanoparticles (SLN) loaded with doxorubicin were prepared by solvent
      emulsification-diffusion method. Glyceryl caprate (Capmul)MCM C10) was used as
      lipid core, and curdlan as the shell material. Dimethyl sulfoxide (DMSO) was used
      to dissolve both lipid and drug. Polyethylene glycol 660 hydroxystearate
      (Solutol)HS15) was employed as surfactant. Major formulation parameters were
      optimized to obtain high quality nanoparticles. The mean particle size measured
      by photon correlation spectroscopy (PCS) was 199nm. The entrapment efficiency
      (EE) and drug loading capacity (DL), determined with fluorescence spectroscopy,
      were 67.5+/-2.4% and 2.8+/-0.1%, respectively. The drug release behavior was
      studied by in vitro method. Cell viability assay showed that properties of SLN
      remain unchanged during the process of freeze-drying. Stability study revealed
      that lyophilized SLN were equally effective (p<0.05) after 1 year of storage at 4
      degrees C. In conclusion, SLN with small particle size, high EE, and relatively
      high DL for doxorubicin can be obtained by this method.

PMID- 19406232
TI  - In vitro and in vivo evaluation of nimesulide lyophilized orally disintegrating
      tablets.
AB  - Development of a lyophilized orally disintegrating tablet (ODT) that enhanced the
      in vitro dissolution and in vivo absorption of nimesulide (NM), a drug with poor
      solubility and poor bioavailability, is presented. The ODTs were prepared by
      freeze-drying an aqueous dispersion of NM containing a matrix former, a sugar
      alcohol, and a collapse protectant. In addition, different disintegration
      accelerators were tested. The influence of formulation parameters on the
      disintegration time and in vitro dissolution of NM from ODTs along with other
      tablet characteristics was investigated. Results obtained from disintegration and
      dissolution studies showed that lyophilized ODTs disintegrated within few seconds
      and showed significantly faster dissolution rate of NM compared to the plain
      powder drug and NM in commercially available immediate release tablet Sulide. The
      ODTs were also examined using differential scanning calorimetry, X-ray
      diffraction, and scanning electron microscope. Stability results, after 12-month
      storage of selected ODTs at 25 degrees C and 60% relative humidity, were
      satisfactory. The extent of absorption of NM from a selected ODT when compared to
      an conventional immediate release tablet as a reference after administration of
      100mg oral dose of NM was determined in healthy subjects using a randomized
      crossover design. In this study, the rate of absorption of NM from ODT was faster
      than that from the reference tablet, had a significantly higher (p=0.012) peak
      plasma concentration, and shortened time to C(max) by 1h (p=0.029). The extent of
      absorption expressed by AUC was 62% larger when compared to the commercially
      available tablet.

PMID- 19406233
TI  - Quantification of microparticle coating quality by confocal laser scanning
      microscopy (CLSM).
AB  - In this work, a novel protocol was developed for determining film coating
      thickness and coating quality of microparticles, based on the use of confocal
      laser scanning microscopy (CLSM). CLSM was found to be an adequate non
      destructive technique for the quantification of the coating thickness and coating
      quality of individual thin-coated small particles. Combined with image analysis,
      it was possible to derive with high accuracy the coating thickness distribution
      of a representative number of microparticles. The performance of the novel
      methodology was assessed by the quantification of the coating thickness and
      coating quality of protein-coated microparticles produced by fluidized bed
      coating. It was found that the CLSM data on coating layer thickness were
      generally in good agreement with the results from chemical analysis, down to a
      thickness of 1-1.5 microm. Using CLSM the importance of setting up the
      appropriate distance between the coating nozzle and the powder bed with respect
      to microparticle coating quality in fluidized bed processing was illustrated.
      Coating quality was found to decrease with increasing distance the coating
      droplets have to travel before impinging onto the core particles as a result of
      spray-drying of the coating droplets. Also, coating quality decreased with
      increasing viscosity of the coating droplets, resulting in reduced spreading on
      the cores.

PMID- 19406234
TI  - Colon targeting with bacteria-sensitive films adapted to the disease state.
AB  - The aim of this study was to identify novel polymeric films allowing for the site
      specific delivery of drugs to the colon of patients suffering from inflammatory
      bowel diseases. Ethylcellulose was blended with different types of bacteria
      sensitive starch derivatives. The water uptake and dry mass loss kinetics of the
      systems were monitored upon exposure to media simulating the contents of the
      stomach, small intestine and colon (including fresh fecal samples from Crohn's
      Disease and Ulcerative Colitis patients). Importantly, ethylcellulose:Nutriose FB
      06 and ethylcellulose:Peas starch N-735 films showed highly promising water
      uptake and dry mass loss kinetics in all the investigated media, indicating their
      potential to minimize premature drug release in the upper gastro-intestinal
      tract, and allowing for controlled release once the colon is reached. This can be
      attributed to the fact that the starch derivatives serve as substrates for the
      enzymes, which are secreted by the bacteria present in the colon of inflammatory
      bowel disease patients. Thus, the identified new polymeric films are adapted to
      the pathophysiological conditions in the gastro-intestinal tract in the disease
      state. Furthermore, Nutriose is known to provide pre-biotic effects, which can be
      of great benefit for these patients.

PMID- 19406235
TI  - Characterization and superficial transformations on mini-matrices made of
      interpolymer complexes of chitosan and carboxymethylcellulose during in vitro
      clarithromycin release.
AB  - Different interpolymer complexes (IPCs) of chitosan (CS) and
      carboxymethylcellulose sodium salt (CMC) were used to elaborate mini-matrices
      containing clarithromycin (CAM). IPCs were characterized by FTIR, DSC and powder
      X-ray (XRD). Compression processes did not modify the physical state of CAM which
      was in its polymorph Form II. However, during tableting, polymer/polymer
      interactions occurred to form matrix systems that were confirmed by DSC. When
      mini-matrices were placed in acetate buffer (pH 4.2), the formation of a CAM
      solvate was determined by XRD, FTIR and DSC, showing the presence of incorporated
      crystallizing solvent molecules. Grazing incidence X-ray diffraction (GID)
      enabled us to profile transformations of CAM on surfaces of mini-matrices when it
      is in intimate contact with dissolution medium, and its conversion to a solvate
      form prior to its dissolution process. Besides, FTIR and DSC revealed polymer
      polymer electrostatic interactions during dissolution process. Furthermore,
      swelling and eroding studies and in vitro drug release exhibited that when
      increasing the amount of CS within IPCs, swelling and erosion rates were greater
      and CAM release was faster. Zero-order kinetics from drug release profiles were
      related to linear erosion kinetics, and highlighted that erosion played an
      important role in drug release due to CAM poor solubility at this pH.

PMID- 19406236
TI  - Systematical approach of formulation and process development using roller
      compaction.
AB  - The roller compaction process has gained heightened interest in the
      pharmaceutical industry. In this review, common excipients and equipment used for
      dry granulation are described. Roller compaction process parameters and their
      impact on the critical quality attributes of the final product, as well as
      evaluation methods for roller compaction product such as ribbons and granules,
      are discussed. Overall, a systematical approach of formulation and process
      development has been proposed for excipient selection, critical process parameter
      identification, and necessary tests.

PMID- 19406237
TI  - Development and characterization of extended release Kollidon SR mini-matrices
      prepared by hot-melt extrusion.
AB  - Kollidon SR as a drug carrier and two model drugs with two different melting
      points, ibuprofen and theophylline, were studied by hot-melt extrusion. Powder
      mixtures containing Kollidon SR were extruded using a twin-screw extruder at
      temperatures 70 and 80 degrees C for ibuprofen and 80 and 90 degrees C for
      theophylline. The glass transition temperature (T(g)) and maximum torque were
      inversely related to ibuprofen concentrations, indicating its plasticizing
      effect. The results of differential scanning calorimetry (DSC) and X-ray
      diffraction analysis showed that ibuprofen remained in an amorphous or dissolved
      state in the extrudates containing drug up to 35%, whereas theophylline was
      dispersed in the polymer matrix. The increase in amounts of ibuprofen or
      theophylline in the hot-melt extrudates resulted in the increase in the drug
      release rates. Theophylline release rate in hot-melt extruded matrices decreased
      as the extrusion temperature increased. In contrast, a higher processing
      temperature caused the higher ibuprofen release. This was a clear indication of
      the plasticizing effect of ibuprofen on Kollidon SR and a result from water
      uptake. Theophylline release rate from hot-melt extrudates decreased with
      increasing triethyl citrate (TEC) level because of the formation of a denser
      matrix. By adding of Klucel LF as a water-soluble additive to the hot-melt
      extruded matrices, an increase in ibuprofen and theophylline release rates was
      obtained.

PMID- 19406238
TI  - Estrogen receptor polymorphism, estrogen content and idiopathic scoliosis in
      human: a possible genetic linkage.
AB  - Idiopathic scoliosis (IS) is a largely diffused disease in human population but
      its pathogenesis is still unknown. There is a relationship between scoliotic
      phenotype and the patient age, since in the early stage the pathology shows a
      ratio of 50% between male and female teenagers. During puberty the sex ratio is
      8.4/1 (female/male), suggesting a sex-conditioned manifestation of the disease.
      Genetic inheritance of idiopathic scoliosis is still unclear although some
      authors claim for its X-linked dominant inheritance. There is large agreement in
      considering the IS as a sex-conditioned disease, in terms of steroid content and
      their receptor activity, although no evidence has been found yet. The blood
      content of 17beta-estradiol in teenagers with IS shows lower levels than
      teenagers of the same age without IS. Also testosterone and progesterone content
      are lower in IS girls with respect to the control girls. Furthermore, we
      extracted DNA from white blood cells of IS patients and their relatives until the
      third generation in order to examine estrogen receptor alpha polymorphisms,
      considering this tool a plausible molecular marker for IS prognosis. In this
      respect, we identified four polymorphisms in the exons encoding for the steroid
      binding domain and two other in the trans-activation domain. Our results show a
      clear relationship with clinical manifestation of IS.

PMID- 19406240
TI  - Differential expression of determinants of glucocorticoid sensitivity in androgen
      dependent and androgen-independent human prostate cancer cell lines.
AB  - Glucocorticoids (GCs) are widely used for the treatment of hormone refractory
      prostate cancer. However, few data are available on the expression and regulation
      of glucocorticoid and mineralocorticoid receptors (GR and MR) and 11beta
      hydroxysteroid dehydrogenase (11beta-HSD) 1 and -2 activities in prostate cancer
      cells. Here we show that GR is expressed in both the androgen-independent PC-3
      cell line and, at very low levels, in the androgen-dependent LNCaP cells, and MR
      is expressed in both cell lines. IL-1beta increased GR expression in both cell
      lines. In LNCaP cells IL-1beta also increased MR expression. Significant 11beta
      HSD oxidase activity and 11beta-HSD2 protein were found in LNCaP cells, but not
      in PC3 cells, and no ketoreductase activity was detected in either cell lines. GR
      function was assessed by measuring the inhibitory effect of dexamethasone on
      constitutive and IL-1beta-inducible IL-6 and osteoprotegerin (OPG) production. In
      PC-3 cells, IL-1beta stimulated IL-6 and OPG release, and dexamethasone dose
      dependently inhibited IL-1beta-inducible IL-6 release, and constitutive and IL
      1beta-inducible OPG release. In LNCaP cells, IL-1beta stimulated only OPG
      release. While dexamethasone was ineffective, cortisol dose-dependently inhibited
      IL-1beta-inducible OPG release. Eplerenone (Epl), a selective mineralocorticoid
      antagonist, reverted this effect. We conclude that different patterns of
      expression of receptors and 11beta-HSD activity were associated with different
      responsiveness to GCs in terms of regulated gene expression. GR and MR expression
      may vary as a function not only of the malignant phenotype, but also of local
      conditions such as the degree of inflammation. Inhibition of IL-6 and OPG release
      by GCs may contribute to the antitumor efficacy in prostate cancer.

PMID- 19406239
TI  - Assisted reproduction technologies impair placental steroid metabolism.
AB  - The placenta plays a vital role in pregnancy by facilitating steroid passage from
      maternal to fetal circulation and/or direct production of hormones. Using a
      murine model, we demonstrated the differences in placental steroid metabolism
      between pregnancies conceived naturally and with assisted reproduction
      technologies (ART): in vitro fertilization (IVF) and intracytoplasmic sperm
      injection (ICSI). While the ovarian steroid production was similar (estrone,
      17beta-estradiol) or higher (estriol) in ART pregnancies compared to mating, the
      levels of placental estriol were significantly lower in ART group. Placentas from
      ART had significantly higher activities of the steroid metabolizing enzymes UDP
      glucuronosyltransferase (UGT) and sulfotransferase (SULT), which in ICSI were
      also coupled with decreased activity of the steroid regenerating enzymes beta
      glucuronidase (beta-G) and aryl sulfatase (AS). Levels of steroid metabolites
      androstane-3alpha-17beta-diol glucuronide and dehydroepiandrosterone sulfate were
      higher in fetal compared to maternal blood in ART, but not in mating. This study
      demonstrates that in murine ART pregnancies, higher metabolism and clearance of
      steroids by the placenta may seriously affect the passage of essential hormones
      to the fetus. If a similar phenomenon exists in humans, this could provide a
      plausible explanation for obstetric and neonatal complications associated with
      ART, including the higher incidence of low birth weight babies.

PMID- 19406242
TI  - Evidence that low-dose, long-term genistein treatment inhibits oestradiol
      stimulated growth in MCF-7 cells by down-regulation of the PI3-kinase/Akt
      signalling pathway.
AB  - The reduced incidence of breast cancer in certain Eastern countries has been
      attributed to high soy diets although this evidence is simply epidemiological.
      One of the major constituents of soy is genistein, but paradoxically this
      phytoestrogen binds to oestrogen receptors and stimulates growth at
      concentrations that would be achieved by a high soy diet, but inhibits growth at
      high experimental concentrations. To determine the effects of low-dose, long-term
      genistein exposure we have cultured MCF-7 breast cancer cells in 10 nM genistein
      for 10-12 weeks and investigated whether or not this long-term genistein
      treatment (LTGT) altered the expression of oestrogen receptor alpha (ERalpha) and
      the activity of the PI3-K/Akt signalling pathway. This is known to be pivotal in
      the signalling of mitogens such as oestradiol (E(2)), insulin-like growth factor
      1 (IGF-1) and epidermal growth factor (EGF). LTGT significantly reduced the
      growth promoting effects of E(2) and increased the dose-dependent growth
      inhibitory effect of the PI3-K inhibitor, LY 294002, compared to untreated
      control MCF-7 cells. This was associated with a significant decreased protein
      expression of total Akt and phosphorylated Akt but not ERalpha. Rapamycin, an
      inhibitor of one of the down-stream targets of Akt, mammalian target of rapamycin
      (mTOR), also dose-dependently inhibited growth but the response to this drug was
      similar in LTGT and control MCF-7 cells. The protein expression of liver receptor
      homologue-1 (LRH1), an orphan nuclear receptor implicated in tumourigenesis was
      not affected by LTGT. The results show that LTGT results in a down-regulation of
      the PI3-K/Akt signalling pathway and may be a mechanism through which genistein
      could offer protection against breast cancer.

PMID- 19406241
TI  - Steroid production and excretion by the pregnant mouse, particularly in relation
      to pregnancies with fetuses deficient in Delta7-sterol reductase (Dhcr7), the
      enzyme associated with Smith-Lemli-Opitz syndrome.
AB  - This study has shown that the mouse has a great increase in steroid production
      during pregnancy in similar fashion to the human. Many steroids were
      provisionally identified in maternal urine of the wild-type mouse. The major
      progesterone metabolites appear to be hydroxylated pregnanolones, particularly
      with hydroxyl groups in the 16alpha position. Rather than estriol being the major
      end-product of feto-placental steroid synthesis as in the human, the pregnant
      mouse produces and excretes large amounts of androgen metabolites, ranging in
      polarity from androstanetriols to androstanepentols. These steroids have 15alpha-
      or 18-hydroxyl groups with additional hydroxylation at uncharacterized positions.
      From metabolite data the peak of pregnancy progesterone production appears to be
      between 7.5 and 14.5 gestational days, while for C(19) metabolites peak excretion
      is later. The starting-point of the studies was to study pregnancy steroid
      production by a mouse model for Smith-Lemli-Opitz syndrome, 7-dehydrosterol
      reductase (DHCR7) deficiency. In human pregnancies with DHCR7 deficient fetuses
      large amounts of 7- and 8-dehydrosteroids are excreted, products secondary to
      high fetal 7- and 8-dehydrocholesterol (DHC) accumulation. This agrees with
      existing evidence that human feto-placental steroid synthesis utilizes little
      maternal cholesterol as precursor. In contrast, this study has shown that
      pregnant mice carrying dhcr7 deficient fetuses with relatively high DHC
      production had essentially undetectable maternal excretions of steroids with
      Delta(7)- and Delta(8)-unsaturation. As mutant mouse mothers have essentially
      normal cholesterol production (little or no DHC build-up), this suggests maternal
      cholesterol is primarily utilized for pregnancy steroid synthesis in the mouse.

PMID- 19406243
TI  - Human macrophage cholesterol efflux potential is enhanced by HDL-associated
      17beta-estradiol fatty acyl esters.
AB  - High-density lipoprotein (HDL) and 17beta-estradiol independently provide
      protection against atherosclerosis. Estradiol fatty acyl esters incorporate into
      HDL and whether this association enhances the atheroprotective properties of HDL
      is unclear. The study objective was to clarify the role that HDL-associated
      estradiol fatty acyl esters play in mediating the initial steps of reverse
      cholesterol transport. Cholesterol efflux potential from cholesterol loaded
      macrophage cells to HDL-associated estradiol ester or between HDL from
      premenopausal women and age-matched males and the cellular receptors involved
      were examined. Human THP-1 macrophages, loaded with [(3)H]cholesterol oleate,
      acetylated low-density lipoprotein, were pretreated with or without SR-BI
      inhibitors or an estrogen receptor antagonist and incubated with either HDL
      associated estradiol oleate, HDL lacking estradiol oleate, or isolated HDL from
      females and males, and cholesterol efflux was measured. Cellular internalization
      and hydrolysis of HDL-associated [(3)H]estradiol ester were determined. HDL
      associated estradiol oleate and premenopausal female HDL demonstrated
      significantly higher cholesterol efflux capacity to media than male HDL. SR-BI
      and estrogen receptor inhibition significantly reduced this effect. Cells
      internalized and subsequently hydrolyzed HDL-associated [(3)H]estradiol ester to
      [(3)H]estradiol and again SR-BI inhibition reduced this internalization. These
      results demonstrate that HDL-mediated macrophage cholesterol efflux potential is
      enhanced by HDL-associated estradiol esters.

PMID- 19406244
TI  - Induction of the adrenoleukodystrophy-related gene (ABCD2) by thyromimetics.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by
      mutations in the ABCD1 (ALD) gene. The ABCD2 gene, its closest homolog, has been
      shown to compensate for ABCD1 deficiency when overexpressed. We previously
      demonstrated that the ABCD2 promoter contains a functional thyroid hormone
      response element. Thyroid hormone (T3) through its receptor TRbeta can induce
      hepatic Abcd2 expression in rodents and transiently normalize the VLCFA level in
      fibroblasts of Abcd1 null mice. In a therapeutic perspective, the use of
      selective agonists of TRbeta should present the advantage to be devoid of side
      effects, at least concerning the cardiotoxicity associated to TRalpha activation.
      In this study, we compared the effects of T3 with those of two thyromimetics (GC
      1 and CGS 23425) specific of TRbeta. Using a gene reporter assay, we demonstrated
      that the rat Abcd2 promoter responds to the thyromimetics in a dose-dependent way
      similar to what is observed with T3. We then investigated the effects of 2-, 4-
      and 10-day treatments on the expression of ABCD2 and its paralogs ABCD3 and ABCD4
      in human cell lines by RT-qPCR. Both thyromimetics trigger up-regulation of ABCD2
      4 genes in HepG2 cells and X-ALD fibroblasts. Interestingly, in X-ALD
      fibroblasts, while T3 is associated with a transient induction of ABCD2 and
      ABCD3, the treatments with thyromimetics allow the induction to be maintained
      until 10 days. Further in vivo experiments in Abcd1 null mice with these
      thyromimetics should confirm the therapeutic potentialities of these molecules.

PMID- 19406245
TI  - Ectodomain orientation, conformational plasticity and oligomerization of ErbB1
      receptors investigated by molecular dynamics.
AB  - Epidermal growth factor receptor (EGFR; ErbB1, HER1 in humans) is a receptor
      tyrosine kinase triggering signals across the plasma membranes of cells to
      determine cell fate. We have used molecular dynamics simulations to investigate
      structural models of ErbB1 ectodomains. We show that, with minor rearrangements,
      the ErbB1 back-to-back dimer can align almost flat on the cell membrane. This is
      in contrast to the traditional picture of ErbB1 dimers standing proud of the
      membrane, but in line with recent FRET and EM experiments. Interaction with the
      membrane leads to conformational changes in the dimer, which further stabilize
      the back-to-back interface. On the membrane, two dimers can associate forming a
      tetramer. This is enabled by a head-to-head interface, involving the ligand
      binding side of the ectodomain, and which significantly enhances ligand binding.
      A weak head-to-head interface has been seen in crystal structures, but is found
      to stabilise appreciably in our simulation. We also find that the domains IV,
      connecting the receptor to the membrane, weakly interact with each other. These
      simulations illustrate some of the flexibility of the ErbB1 ectodomains, and may
      help to explain recent experimental results.

PMID- 19406246
TI  - Lipopeptides derived from HIV and SIV mimicking the prehairpin intermediate of
      gp41 on solid supported lipid bilayers.
AB  - We present a universal mimetic approach of the prehairpin intermediate of gp41,
      which represents the active drug target for fusion inhibitors of HIV (human
      immunodeficiency virus) and SIV (simian immunodeficiency virus) based on membrane
      anchored lipopeptides. For this purpose, we have in situ coupled terminal
      cysteine-modified peptides originating from the NHR of SIV and HIV to a maleimide
      functionalized DOPC bilayer and monitored the interactions with potential
      antagonists of the trimer-of-hairpin conformation C34 and T20 peptides by means
      of atomic force microscopy and ellipsometry. FT-IR analysis in conjugation with
      CD-spectroscopy of hydrated N36-lipopeptides, incorporated in multilamellar
      bilayer stacks was employed to investigate peptide conformation prior to
      antagonist binding. In contrast to solution studies substantial secondary
      structure formation of S-N36 after in situ coupling to the bilayer was found. We
      could show that S-N36-lipopeptide-aggregates in bilayers were selectively able to
      bind T20 or the corresponding C-peptides (C34) and similar results could be
      achieved by using H-N36 lipopeptides. It was found that T20 binding to coiled
      coil S-N36 lipopeptide assemblies was fully reversible at elevated temperatures,
      while T20 binds irreversibly to H-N36 bundles.

PMID- 19406247
TI  - Surveillance and trends of antimicrobial resistance among clinical isolates of
      anaerobes in Kuwait hospitals from 2002 to 2007.
AB  - The susceptibility trends for all anaerobes processed by the Anaerobe Reference
      Laboratory against various antibiotics were determined by using data for 2557
      isolates referred by all government hospitals in Kuwait from 2002 to 2007. MIC
      were determined for the following anti-anaerobic antibiotics: amoxicillin
      clavulanic acid, clindamycin, imipenem, meropenem, metronidazole, penicillin,
      piperacillin, piperacillin-tazobactam and vancomycin (for Gram-positive anaerobes
      only), using E-test method. The commonest isolates were Bacteroides fragilis
      (36.8%), followed by Peptostreptococcus spp. (21.9%), Bacteroides ovatus (15.5%)
      and Prevotella bivia (12.1%). In addition, Prevotella oralis and other
      Bacteroides spp. represented 8.5% and 8.1% of total number of isolates,
      respectively. Resistance rate varied among the antimicrobial agents and the
      species tested. The beta-lactams, with the exception of penicillin, were the most
      active drugs. Piperacillin-tazobactam was the only antimicrobial agent to which
      all the isolates were uniformly susceptible. Imipenem and metronidazole were
      highly active with resistance rate of only <5% recorded against most isolates.
      However, 42.8, 55.8 and 9.3% of Clostridium difficile isolates were resistant to
      imipenem, clindamycin and meropenem, respectively. It is noteworthy that from
      2002 to 2007, there was a gradual increase in resistance rates to clindamycin,
      amoxicillin-clavulanic acid and piperacillin among B. fragilis. Periodic
      surveillance of antibiotic resistance among the anaerobic bacteria is recommended
      as a guide to empiric antibiotic use and formulation of guideline for appropriate
      choice of antimicrobial therapy in anaerobic infections.

PMID- 19406248
TI  - Autophagy and plant innate immunity: Defense through degradation.
AB  - Autophagy is a process of bulk degradation and nutrient sequestration that occurs
      in all eukaryotes. In plants, autophagy is activated during development,
      environmental stress, starvation, and senescence. Recent evidence suggests that
      autophagy is also necessary for the proper regulation of hypersensitive response
      programmed cell death (HR-PCD) during the plant innate immune response. We review
      autophagy in plants with emphasis on the role of autophagy during innate
      immunity. We hypothesize a role for autophagy in the degradation of pro-death
      signals during HR-PCD, with specific focus on reactive oxygen species and their
      sources. We propose that the plant chloroplasts are an important source of pro
      death signals during HR-PCD, and that the chloroplast itself may be targeted for
      autophagosomal degradation by a process called chlorophagy.

PMID- 19406250
TI  - Nutrient profiling reveals potent inducers of trichothecene biosynthesis in
      Fusarium graminearum.
AB  - Fusarium head blight is one of the most important diseases of wheat worldwide due
      to crop losses and the contamination of grains with trichothecene mycotoxins. The
      biosynthesis of trichothecenes by Fusarium spp. is highest during infection, but
      relatively low levels are produced from saprophytic growth in axenic culture. A
      strain of Fusarium graminearum was constructed where the promoter from the TRI5
      trichothecene biosynthesis gene was fused to GFP. Using this strain in large
      scale nutrient profiling, a variety of amines were identified that significantly
      induce TRI5 expression. Analysis of trichothecene levels in the culture filtrates
      revealed accumulation of the toxin to over 1000ppm in response to these inducers,
      levels either greater than or equivalent to those observed during infection. From
      this work, we propose that products of the arginine-polyamine biosynthetic
      pathway in plants may play a role in the induction of trichothecene biosynthesis
      during infection.

PMID- 19406251
TI  - Epilepsy and sudden death: personal reflections and call for global action.
AB  - To solve the mystery of sudden unexpected death in persons with epilepsy (SUDEP),
      a global focus is needed to identify persons at risk, develop treatment regimens,
      and prevent its occurrence. A world wide network of professionals must focus on
      basic scientific research programs and clinical and epidemiology studies. Team
      work among different multidisciplinary professionals in clinical settings and
      within and among laboratories should address the global issues of SUDEP. If the
      correct term 'SUDEP' is used on autopsy reports and if verbal autopsies
      postmortem are conducted when needed, the true incidence of SUDEP may be found to
      be much higher than previously thought and the market for new antiepileptics and
      other drugs to prevent SUDEP will be larger. Symposia should discuss new data and
      lessons learned from the last 20 to 30 years to be applied by scientists and
      clinicians worldwide to gain a better understanding of SUDEP. 'Think out of the
      box' when evaluating an established animal model with potential for
      modification(s) to study mechanism(s) of SUDEP. Multiple relevant animal models
      are needed to understand the pathophysiology of SUDEP, hypothesize about
      effective treatments, develop small pilot studies in persons with epilepsy, and
      conduct confirmatory large-scale clinical trials. The fields of pharmacology,
      clinical pharmacology, and cardiology have much to offer as we work to improve
      compliance, develop new antiepileptic drugs, and apply different categories of
      drugs to resolve the mystery of SUDEP. Ambulatory simultaneous EKG and EEG
      telemetry monitoring of patients at risk for sudden death will help identify
      cardiac vs. brain epileptogenic triggers for treatment to decrease risk of SUDEP.
      Respiratory function monitoring is also needed. Academic fellowships and
      competitions for medical students, postdoctoral fellows, residents and faculty
      will attract medical and graduate trainees to work on SUDEP. Grant funding is
      essential to move the SUDEP knowledge base forward. Leaders must solve the global
      mystery of SUDEP using a leadership philosophy foundation that provides
      innovative vision and approaches for SUDEP research and teaching programs. The
      interaction of teaching and research is essential: while a student is learning
      how to conduct research he must simultaneously learn to become a teacher. Medical
      and graduate leaders must provide vision and a fertile environment to teach
      students of today to become the self learners and leaders of tomorrow to find
      solutions for SUDEP.

PMID- 19406252
TI  - The brainstem respiratory network: an overview of a half century of research.
AB  - This review aims at summarizing the work performed over 40 years by Professor
      Armand Bianchi and the research team he directed, which was devoted to the study
      of the central respiratory network. The major steps towards the understanding of
      this complex network will be presented together with methodological
      considerations. This includes the sequential progress that was made in the
      identification and characterization of respiratory neurons as deduced from
      inferences gleaned from intracellular recordings, which revealed putative
      synaptic connections within the respiratory network. Also reviewed is a
      comparison of in vivo versus in vitro approaches. The search for the "real"
      respiratory neurons must consider that those neurons are redundantly represented
      within the brainstem and express a wide variety of patterns. The last part of
      this review focuses on the concept that the brainstem respiratory circuitry forms
      part of a multifunctional network subserving both respiration and non-respiratory
      motor behaviors. Numerous data provide evidence that the respiratory network
      operates as a dynamic assembly of neurons, some of which can belong to several
      networks involved in the coordination of respiratory muscles during functions
      that include coughing, swallowing and vomiting.

PMID- 19406253
TI  - Structure-function analysis of rhythmogenic inspiratory pre-Botzinger complex
      networks in "calibrated" newborn rat brainstem slices.
AB  - Inspiratory pre-Botzinger complex (preBotC) networks remain active in perinatal
      rodent brainstem slices. Our analysis of (crescendo-like) inspiratory-related
      population and cellular bursting in novel histologically identified transversal
      preBotC slices in physiological (3 mM) superfusate [K(+)] revealed: (i) the
      preBotC extent sufficient for rhythm in thin slices is at most 175 microm. (ii)
      In 700 microm thick slices with unilaterally exposed preBotC, a <100 microm
      kernel generates a eupnea-like inspiratory pattern under predominant influence of
      caudally adjacent structures or thyrotropin-releasing hormone-like transmitters,
      but a mixed eupnea-sigh-like pattern when influence of rostral structures or
      substance-P-like transmitters dominates. (iii) Primarily presynaptic processes
      may underlie inhibition of rhythm by opioids or raising superfusate [Ca(2+)] from
      lower to upper physiological limits (1-1.5 mM). (iv) High K(+) reverses
      depression of rhythm by raised Ca(2+), opioids and anoxia. In summary, distinct
      activity patterns of spatiochemically organized isolated inspiratory networks
      depend on both an extracellular "Ca(2+)-K(+) antagonism" and slice dimensions.
      This explains some discrepant findings between studies and suggests use of
      "calibrated" slices and more uniform experimental conditions.

PMID- 19406254
TI  - Respiratory muscle activity and dyspnea during exercise in chronic obstructive
      pulmonary disease.
AB  - We aimed to determine by non-invasive EMG, whether during exercise: (1) COPD
      patients increase scalene and intercostal EMG activity, (2) increased EMG
      activity is associated with increased dyspnea, and (3) the ratio between EMG
      activity and volume displacement is increased in COPD compared to healthy
      subjects (HS). During a maximal incremental cycle test, scalene and intercostal
      EMG was derived transcutaneously in 17 COPD patients and 10 HS. Dyspnea was
      quantified using a Borg scale, ranging from zero to 10 (maximal dyspnea). For
      analyses the ratio between inspiratory muscle activity during exercise and
      activity during quiet breathing was used (logEMGAR). In COPD patients, scalene
      and intercostal activity increased at greater rate early in exercise compared to
      that of the HS. With a doubling of the logEMGAR, in COPD, dyspnea increased with
      2.8/3.8 points, while in the HS, dyspnea increased less with 1.1/1.4 points. In
      COPD, there was a larger increase in EMG activity relatively to tidal volume
      increases.

PMID- 19406255
TI  - Notch signaling during chondrogenesis of human bone marrow stem cells.
AB  - Notch signaling is an important mechanism involved in early development which
      helps to determine the differentiation and fate of cells destined to form
      different tissues in the body. Its role in the differentiation of adult stem
      cells, such as those found in bone marrow is much less clear. As there is great
      interest in the potential of human bone marrow stem cells (hMSC) as a source of
      cells for the repair of articular cartilage and other tissues, it is important to
      understand if Notch signaling promotes or suppresses differentiation. Using
      primary human bone marrow stem cells (hMSC) in 3D cell aggregate culture a new
      study has investigated the expression of the canonical Notch pathway genes during
      chondrogenesis and showed that the Notch ligand, Jagged1 (JAG1) sharply increased
      in expression peaking early in differentiation. A Notch target gene, HEY1, was
      also expressed with a temporal profile, which closely followed the expression of
      JAG1 and this preceded the rise in type II collagen expression that characterized
      chondrogenesis. The JAG1 mediated Notch signaling was shown with a Notch
      inhibitor (DAPT) to be necessary for chondrogenesis, as inhibition days 0-14, or
      just days 0-5, blocked chondrogenesis, whereas Notch inhibition days 5-14 did
      not. In further experiments Notch signaling was shown to be critical for full
      chondrogenesis, as adenoviral hJAG1 transduction of hMSCs, which caused
      continuous expression of JAG1 and sustained Notch signaling, completely blocked
      chondrogenesis. In these cultures there was inhibited production of extracellular
      matrix and failure to differentiate was interpreted as the retention of the hMSC
      in a pre-chondrogenic state. The results in this study thus showed that JAG1
      mediated Notch signaling in hMSC was necessary to initiate chondrogenesis, but
      must be switched off for chondrogenesis to proceed and it will be important to
      establish if this is a mechanism common to all chondrocyte differentiation.

PMID- 19406256
TI  - Severity of coronary arterial stenoses responsible for acute coronary syndromes.
AB  - Acute myocardial infarctions were generally believed to result from plaque
      rupture and thrombosis at the site of a "mild to moderate" coronary stenosis. To
      assess the severity of coronary stenoses that predisposed to acute coronary
      syndrome, the 317 patients prospectively included were (1) 102 patients with
      acute ST-elevation myocardial infarction (STEMI) referred for primary
      percutaneous coronary intervention (PCI), (2) 135 patients with non-STEMI or
      unstable angina pectoris (UAP) referred for semiurgent PCI, and (3) 80 patients
      with stable angina pectoris (SAP) admitted for elective PCI. Patients with STEMI
      were included if thrombus aspiration could restore normal antegrade coronary
      blood flow. After aspiration (but before PCI), a high-quality angiogram was
      obtained and the reference diameter, minimal luminal diameter, and percentage of
      diameter stenosis of the culprit lesion were quantified. In patients with non
      STEMI/UAP and SAP, aspiration was not performed. Average diameter of stenosis was
      similar in patients with STEMI and those with SAP (66 +/- 12% vs 65 +/- 10%,
      respectively; p = NS), but was slightly larger in patients with non-STEMI/UAP (71
      +/- 12%; p <0.05 vs both STEMI and SAP). In patients with STEMI, only 11% of
      culprit stenoses were found to have diameter stenosis <50% after removal of the
      thrombus. In conclusion, most STEMIs occurred at the site of severe coronary
      stenosis. Diameter stenosis severity was <50% in a minority of cases.

PMID- 19406249
TI  - Bioelectric mechanisms in regeneration: Unique aspects and future perspectives.
AB  - Regenerative biology has focused largely on chemical factors and transcriptional
      networks. However, endogenous ion flows serve as key epigenetic regulators of
      cell behavior. Bioelectric signaling involves feedback loops, long-range
      communication, polarity, and information transfer over multiple size scales.
      Understanding the roles of endogenous voltage gradients, ion flows, and electric
      fields will contribute to the basic understanding of numerous morphogenetic
      processes and the means by which they can robustly restore pattern after
      perturbation. By learning to modulate the bioelectrical signals that control cell
      proliferation, migration, and differentiation, we gain a powerful set of new
      techniques with which to manipulate growth and patterning in biomedical contexts.
      This chapter reviews the unique properties of bioelectric signaling, surveys
      molecular strategies and reagents for its investigation, and discusses the
      opportunities made available for regenerative medicine.

PMID- 19406257
TI  - Incidence, predictors, and outcome of new, subsequent lesions treated with
      percutaneous coronary intervention in patients presenting with myocardial
      infarction.
AB  - Despite improving strategies for control of risk factors, progression of
      atherosclerosis may lead to recurrent cardiac events related to a lesion other
      than that treated with initial percutaneous coronary intervention (PCI) after ST
      elevation myocardial infarction (STEMI). Of 1,007 consecutive patients undergoing
      primary or rescue PCI for STEMI, 897 who were discharged alive were followed for
      up to 3 years. Those who underwent nontarget lesion revascularization (non-TLR)
      were compared with those who did not. Those who underwent a second procedure were
      followed for an additional 1 year. Altogether, 94 patients (10.5%) required a non
      TLR. The median time from the first to the second PCI was 396 days (interquartile
      range 131 to 533). Subsequent PCI was required for non-STEMI in 46.1% and STEMI
      in 9.7% of cases. Independent predictors of need for non-TLR were diabetes
      mellitus, history of coronary bypass surgery, or peripheral vascular disease. By
      1 year after the second PCI, 9 patients (9.6%) died, 4 (4.3%) had sustained MI,
      and 4 (4.3%) had TLR. One of these major adverse events had occurred in 17 (18%).
      In conclusion, after STEMI, nearly 10% of patients will develop an event that
      requires subsequent PCI to an unrelated lesion. Patients with diabetes mellitus,
      history of coronary bypass surgery, or peripheral vascular disease are at
      increased risk for this event. Aggressive preventive and medical management
      should be applied to this population for prevention of these subsequent events.

PMID- 19406258
TI  - Impact of gender and antithrombin strategy on early and late clinical outcomes in
      patients with non-ST-elevation acute coronary syndromes (from the ACUITY trial).
AB  - Women with non-ST-elevation acute coronary syndrome are at increased risk for
      ischemic and bleeding complications compared with men. We examined the impact of
      gender and antithrombotic therapy for non-ST-elevation acute coronary syndrome on
      outcomes in patients in the ACUITY trial. Patients were randomized to heparin
      (unfractionated or enoxaparin) plus a glycoprotein IIb/IIIa inhibitor (GPI),
      bivalirudin plus a GPI, or bivalirudin alone. We compared major bleeding
      unconnected to coronary artery bypass grafting, composite ischemia (death,
      myocardial infarction, or revascularization), and net clinical outcome (composite
      ischemia or bleeding) in (1) men versus women overall and undergoing percutaneous
      coronary intervention (PCI) and (2) women overall and undergoing PCI by
      antithrombotic strategy. Of 13,819 patients enrolled, 4,157 were women (30.1%).
      Women had similar 30-day composite ischemia (7% vs 8%, p = 0.07) but greater 30
      day rates of major bleeding (8% vs 3% p <0.0001) and net clinical outcomes (13%
      vs 10% p <0.0001) than men. One-year composite ischemia and mortality was
      similar. In women, bivalirudin compared with heparin + GPI resulted in less 30
      day major bleeding (5% vs 10%, p <0.0001) but similar composite ischemia (7% vs
      6%, p = 0.15). No differences were observed in rates of 1-year composite ischemia
      or mortality in women who received bivalirudin versus heparin + GPI. Results were
      similar in women undergoing PCI. In conclusion, women had similar 30-day
      mortality and composite ischemia but higher net clinical adverse events due to
      more bleeding complications than men; 1-year mortality was similar for men and
      women. In women, bivalirudin monotherapy compared with a GPI-based strategy
      resulted in significantly decreased bleeding but similar rates of 1-year
      composite ischemia and mortality.

PMID- 19406259
TI  - Acute myocardial infarction and underlying stenosis severity.

PMID- 19406260
TI  - Predicting irreversible left ventricular dysfunction after acute myocardial
      infarction.
AB  - Patients with reduced left ventricular ejection fractions (LVEFs) and previous
      myocardial infarctions or heart failure are at increased mortality risk.
      Implantable cardioverter-defibrillators may mitigate this risk. The aim of this
      study was to identify patient characteristics at the time of presentation with ST
      elevation myocardial infarction (STEMI) that predict irreversible left
      ventricular dysfunction. From January 2003 to December 2005, patients presenting
      with STEMIs and an LVEFs after percutaneous coronary intervention <or=0.4 were
      included (n = 118). Clinical, angiographic, and electrocardiographic
      characteristics at the time of STEMI were evaluated to predict LVEF at >or=90
      days. Multivariate analysis identified post-percutaneous coronary intervention
      LVEF <or=0.3 (odds ratio 5.4, 95% confidence interval 2.1 to 14.1, p = 0.001),
      presentation with Killip class >I (odds ratio 4.4, 95% confidence interval 1.5 to
      12.6, p = 0.006), and Q waves on postrevascularization electrocardiography (odds
      ratio 6.3, 95% confidence interval 1.5 to 26.5, p = 0.011) to be significantly
      more common in the group with LVEFs <or=0.3 at >or=90 days. The presence of all 3
      factors, present in 14 patients (12%), had a positive predictive value of 100%
      that LVEF would be <or=0.3 at >or=90 days. In conclusion, in patients with STEMIs
      referred for catheterization, a post-percutaneous coronary intervention LVEF
      <or=0.3, presentation with Killip class >I, and pathologic Q waves after
      revascularization each predicted that the LVEF measured at >or=90 days would
      remain <or=0.3. The presence of all 3 features had a positive predictive value of
      100%. These findings may identify a high-risk group of patients who might benefit
      from early aggressive therapy such as an implantable cardioverter-defibrillator.

PMID- 19406261
TI  - Impact of gender and age on in vivo virtual histology-intravascular ultrasound
      imaging plaque characterization (from the global Virtual Histology Intravascular
      Ultrasound [VH-IVUS] registry).
AB  - Virtual histology intravascular ultrasound (VH-IVUS) analyses were performed in
      the first 990 patients enrolled in the 3,000+ patient global VH-IVUS Registry to
      assess the impact of gender and age on in vivo VH-IVUS plaque characterization.
      The 990 patients were divided into 3 age group terciles (<58, 58 to 68, and >68
      years) and again divided according to gender. In conclusion, (1) both women and
      men had an increase in plaque with increasing age; (2) at any age, men had more
      plaque than women; (3) percentages of dense calcium and necrotic core increased
      with increasing patient age in both men and women; and (4) gender differences
      were lowest in the oldest tercile (>68 years).

PMID- 19406262
TI  - Prevalence of coronary heart disease in patients with aortic aneurysm and/or
      peripheral artery disease.
AB  - Although the presence of coronary heart disease (CHD) was the major determinant
      of perioperative mortality and long-term prognosis in patients with aortic
      aneurysm (AA) and peripheral artery disease (PAD), the prevalence and severity of
      CHD in patients with individual vascular diseases was unknown. Adenosine
      triphosphate-loading myocardial single-photon emission computed tomography
      therefore was performed in 788 patients with vascular diseases of the aorta and
      peripheral arteries, with AA in 500, PAD localized in the lower-limb arteries in
      183, and combined AA and PAD in 105. Patients with known CHD, such as those with
      previous myocardial infarction or revascularization procedures, were excluded.
      Myocardial single-photon emission computed tomography was analyzed using a 20
      segment model, and summed stress scores and summed difference scores were
      calculated. Stress-induced myocardial ischemia was defined as a summed difference
      score >or=2. The presence of myocardial ischemia was highest in patients with
      combined PAD and AA (73%), followed by PAD (55%; p = 0.005), and the lowest in
      patients with AA (37%; p <0.0001). Summed stress score was also the highest in
      patients with combined PAD and AA (11.6 +/- 9.9), followed by PAD (7.8 +/- 8.8; p
      <0.0001), and the lowest in patients with AA (4.0 +/- 6.2; p <0.0001 for both).
      Similarly, summed difference score was the highest in patients with combined PAD
      and AA (6.4 +/- 6.1), followed by PAD (4.4 +/- 5.7; p = 0.001) and AA (2.3 +/-
      4.0; p <0.0001 for both). In conclusion, the prevalence of CHD in patients with
      PAD was >50%, and although myocardial ischemia was observed in only (1/3) of
      patients with AA, its prevalence not only doubled, but also indicated extensive
      myocardial ischemia when combined with PAD. Thus, cardiac evaluation was
      particularly important in patients with combined AA and PAD.

PMID- 19406263
TI  - Impact of plaque characteristics analyzed by intravascular ultrasound on long
      term clinical outcomes.
AB  - Limited data are available on long-term outcomes for vulnerable plaque analyzed
      by intravascular ultrasound (IVUS). The aim of this study was to investigate long
      term clinical outcomes in 183 patients (79 with stable angina pectoris and 104
      with acute coronary syndromes) who underwent preintervention 3-vessel IVUS and
      single-vessel stent implantation. Critical events, defined as any cause of death
      and acute coronary syndromes during follow-up, were evaluated. Plaque
      characteristics were analyzed in the target vessel and nontarget vessels.
      Vulnerable plaques were arbitrarily defined as plaques with rupture, lipid core,
      dissection, or thrombus. The mean follow-up period was 50 +/- 20 months. Critical
      events developed in 12 patients (7%; 6 acute coronary syndromes, 6 deaths). The
      critical event-free rate was not different according to the presence of
      vulnerable plaques in the target lesion (95% vs 95%, p = 0.86). However, in the
      nontarget vessels, the long-term critical event-free rate was significantly lower
      in patients with vulnerable plaques (88% vs 96%, p = 0.04). On multivariate Cox
      regression analysis, the multiplicity of vulnerable plaques in the nontarget
      vessels (hazard ratio 2.2, 95% confidence interval 1.4 to 3.4, p = 0.001) was the
      only independent predictor of long-term critical events. Acute coronary syndromes
      (odds ratio 5.4, 95% confidence interval 2.1 to 14.3, p = 0.001) and diabetes
      mellitus (odds ratio 5.2, 95% confidence interval 1.9 to 13.8, p = 0.001) were
      significantly associated with the multiplicity of vulnerable plaques. In
      conclusion, the multiplicity of vulnerable plaques in nontarget vessels was the
      most important predictor of future critical cardiac events in this 3-vessel IVUS
      study.

PMID- 19406264
TI  - An evidence-based review of the cardiovascular risks of nonsteroidal anti
      inflammatory drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs), both nonselective and
      cyclooxygenase-2-specific inhibitors, are commonly used medications for the
      relief of acute and chronic pain associated with a wide range of medical
      conditions. Because of the extensive use of these agents, adverse events that
      occur infrequently may still affect the overall risk/benefit ratio of this class
      of medications. Serious adverse cardiovascular (CV) events have been reported
      with NSAID use, but unfortunately, definitive evidence regarding the precise CV
      risk associated with these drugs, as a class and individually, is lacking.
      Therefore, it is an issue of public health importance that physicians be guided
      by careful assessment of the existing evidence to make reasonable choices in
      prescribing these medications. The investigators review the key clinical trials,
      meta-analyses of clinical trials, and epidemiologic studies on the subject of the
      CV safety of NSAIDs and identify key variables that define the CV risk of the
      NSAIDs. In conclusion, it is important that cardiologists, who are not among
      those physicians frequently prescribing NSAIDs, have a particular responsibility
      to have up-to-date, thoughtfully synthesized information about the CV risks of
      these drugs, especially when administered to patients receiving low-dose aspirin
      for cardioprotection.

PMID- 19406266
TI  - Relation of increased short-term variability of QT interval to congenital long-QT
      syndrome.
AB  - Apart from clinical symptoms the diagnosis and risk stratification in long-QT
      syndrome (LQTS) is usually based on the surface electrocardiogram. Studies have
      indicated that not only prolongation of the QT interval but also an increased
      short-term variability of QT interval (STV(QT)) is a marker for a decreased
      repolarization reserve in patients with drug-induced LQTS. The aims of this study
      were to determine if STV(QT) (1) is higher in patients with LQTS compared with
      controls, (2) if this effect is more pronounced in a high-risk LQTS population,
      and (3) could increase the diagnostic power of the surface electrocardiogram in
      identifying mutation carriers. Forty mutation carriers were compared with age-
      and gender-matched control subjects in the absence of beta-receptor-blocking
      agents. Lead II or V(5) RR and QT intervals from 30 consecutive beats were
      manually measured. STV(QT) was determined from Poincare plots of QT intervals
      (STV(QT) = Sigma|QTn + 1 - QTn|/[30 x radical2]). Compared with controls,
      patients with LQTS had a prolonged QTc interval (449 +/- 41 vs 411 +/- 32 ms, p =
      0.00049) and increased STV(QT) (6.4 +/- 3.2 vs 4.1 +/- 1.6 ms, p = 0.005). In
      patients with the highest risk of clinical events, defined as a QTc interval >500
      ms or symptoms before beta-blocker therapy, STV(QT) was 9 +/- 4 ms. QTc interval
      had a sensitivity of 43% and a specificity of 97% in identifying mutation
      carriers (thresholds 450 ms for men and 460 ms for women). Receiver operator
      characteristic analysis showed that an STV(QT) of 4.9 ms was the optimal cut-off
      value to predict mutation carriers. When incorporating an STV(QT) >4.9 ms for
      those whose QTc interval was within the normal limits, sensitivity to distinguish
      mutation carriers increased to 83% with a specificity of 68%, so that another 15
      mutation carriers could be identified. In conclusion, these are the first results
      in humans showing that STV(QT) is increased in congenital LQTS, this effect is
      increased in patients with symptoms before therapy, and, hence, STV(QT) could
      prove to be a useful noninvasive additive marker for diagnostic screening to
      bridge the gap before results of genetic testing are available.

PMID- 19406267
TI  - Comparison of characteristics and significance of immediate versus early versus
      no recurrence of atrial fibrillation after catheter ablation.
AB  - Atrial fibrillation (AF) recurrences after catheter ablation are common within
      the first month after AF ablation, and inflammatory processes may be related to
      AF genesis. This study aimed to clarify the relation between inflammatory
      processes and recurrence of AF after ablation and to characterize AF recurring
      within 3 days after ablation (immediate AF recurrence).The study included 186
      patients with drug-refractory paroxysmal AF who underwent extensive pulmonary
      vein isolation. Body temperature and C-reactive protein level were measured
      before and consecutively on the first 3 days after ablation. Signs of
      pericarditis or atrial arrhythmias within 3 days after ablation were also
      monitored. Forty-five patients (24%) had immediate AF recurrence (immediate-AF
      recurrence group), 27 (14%) had early recurrence 4 to 30 days after ablation
      (early-AF-recurrence group), and the remaining 114 (61%) had no AF recurrence
      within 1 month after ablation (no-AF-recurrence group). Increases in body
      temperature and C-reactive protein level from baseline in the immediate-AF
      recurrence group were the highest among the 3 groups, and signs of pericarditis
      were observed in 15 of the 45 patients (33%) in the immediate-AF-recurrence
      group. Atrial premature contractions and nonsustained AF occurred most frequently
      in the early-AF-recurrence group. After 6-month follow-up, the AF-free rate was
      greater in the immediate-AF-recurrence group (76%) than in the early-AF
      recurrence group (30%). In conclusion, immediate AF recurrence has an apparently
      different mechanism and impact on midterm outcomes than does early AF recurrence.
      Acute inflammatory changes after ablation may be responsible for immediate AF
      recurrence.

PMID- 19406265
TI  - Associations of dietary long-chain n-3 polyunsaturated fatty acids and fish with
      biomarkers of inflammation and endothelial activation (from the Multi-Ethnic
      Study of Atherosclerosis [MESA]).
AB  - The cardioprotective effects of long-chain n-3 polyunsaturated fatty acids
      (PUFAs) and fish consumption have been observed. However, data on the specific
      associations of these dietary factors with inflammation and endothelial
      activation are sparse. A cross-sectional study was conducted of 5,677 men and
      women from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, including
      African Americans, Caucasians, Chinese, and Hispanics aged 45 to 84 years and
      free of clinical cardiovascular disease. Dietary information was collected using
      a self-administered food frequency questionnaire. Multivariate linear regression
      analyses were used to examine relations between the intake of long-chain n-3
      PUFAs, nonfried fish, and fried fish and biomarkers of inflammation and
      endothelial activation. Long-chain n-3 PUFA intake was inversely associated with
      plasma concentrations of interleukin-6 (p = 0.01) and matrix metalloproteinase-3
      (p = 0.03) independent of age, body mass index, physical activity, smoking,
      alcohol consumption, and dietary variables. Nonfried fish consumption was
      inversely related to C-reactive protein (p = 0.045) and interleukin-6 (p <0.01),
      and fried fish consumption was inversely related to soluble intercellular
      adhesion molecule-1 (p <0.01) but was not associated with other biomarkers after
      adjustment for potential confounders. In conclusion, the results of this study
      suggest that the dietary intake of long-chain n-3 PUFAs and fish is inversely
      associated with concentrations of some biomarkers, reflecting lower levels of
      inflammation and endothelial activation. These results may partially explain the
      cardioprotective effects of fish consumption.

PMID- 19406268
TI  - Relation of plasma midregional proatrial natriuretic peptide to target organ
      damage in adults with systemic hypertension.
AB  - We tested the hypothesis that, in adults with essential hypertension, plasma
      levels of midregional proatrial natriuretic peptide (MR-proANP) are associated
      with target organ damage. MR-proANP is a newly described stable fragment of N
      terminal proatrial natriuretic peptide. Participants included 1,919 adults with
      hypertension identified from the community (1,037 African-Americans, 65 +/- 9
      years of age, 72% women; 882 non-Hispanic whites, 61 +/- 9 years of age, 55%
      women). We measured MR-proANP by an immunoluminometric assay. Measurements of
      target organ damage included the ankle-brachial index (ABI), urinary albumin
      creatinine ratio (UACR), and left ventricular (LV) mass (available only in
      African-Americans). Generalized estimating equations were used to assess whether
      plasma MR-proANP was associated with measurements of target organ damage,
      independent of potential confounding variables. In African-Americans, higher MR
      proANP was significantly associated with lower ABI (p <0.0001), higher UACR (p
      <0.0001), and greater LV mass (indexed to height to the power of 2.7, p <0.0001).
      After adjustment for age, gender, body mass index, systolic blood pressure,
      estimated glomerular filtration rate, smoking history, diabetes mellitus, total
      and high-density lipoprotein cholesterols, medication (blood pressure lowering,
      statin, and aspirin) use, and previous myocardial infarction or stroke, higher MR
      proANP levels remained significantly associated with lower ABI (p = 0.01), higher
      UACR (p = 0.0007), and greater LV mass index (p <0.0001). In non-Hispanic whites,
      higher MR-proANP levels were significantly associated with lower ABI (p = 0.002)
      and greater UACR (p = 0.001), but not after adjustment for the covariates listed
      earlier. In conclusion, plasma MR-proANP may be a marker of target organ damage
      in the setting of hypertension, especially in African-Americans.

PMID- 19406269
TI  - Effects of left ventricular volume overload on mitochondrial and death-receptor
      mediated apoptotic pathways in the transition to heart failure.
AB  - Cardiomyocyte apoptosis has been implicated in the pathogenesis of heart failure
      (HF). This study was performed in patients with left ventricular (LV) volume
      overload at different stages in the development of HF to correlate apoptotic gene
      expression with LV echocardiographic phenotype. LV biopsies were procured from 24
      cardiac surgical patients selected from 4 distinct clinical groups (n = 6) in the
      progression from preserved LV function to HF. Group I consisted of control
      patients with normal LV function (e.g., with atrial myxoma), group II had aortic
      regurgitation with LV hypertrophy and preserved systolic function (ejection
      fraction >50%), group III had aortic regurgitation with LV dysfunction (ejection
      fraction 30% to 40%), and group IV had end-stage HF (ejection fraction <20%).
      Biopsies were used to measure mRNA expression of the genetic regulators of
      mitochondrial (Bad, Bax, Bcl-2, Bcl-xL, and p53) and death-receptor- (Fas and
      tumor necrosis factor receptor 1 [TNFR1]) mediated apoptotic pathways by reverse
      transcription-polymerase chain reaction. Caspase activity was determined using
      specific fluorogenic peptide substrates and immunohistochemistry. Evidence for
      apoptosis was obtained using terminal deoxynucleotidyl transferase deoxyuridine
      triphosphate nick end labeling and in situ oligo ligation assays. Expression of
      proapoptotic factors (Bax, p53, TNFR1), antiapoptotic mitochondrial factor (Bcl
      xL), and caspases 3, 8, and 9 increased progressively during the transition from
      preserved LV function to HF (p <0.05, analysis of variance). No significant
      difference was found for Bad, Bcl-2, or Fas. No evidence of DNA fragmentation was
      identified. In conclusion, activation of the cardiomyocyte apoptotic cascade
      occurs during the development of volume overload-induced HF. Mitochondrial (Bax,
      p53, caspase 9) and death-receptor mediated (TNFR1, caspase 8) pathways are
      upregulated but without completion of DNA fragmentation.

PMID- 19406271
TI  - Usefulness of a combination of systolic function by left ventricular ejection
      fraction and diastolic function by E/E' to predict prognosis in patients with
      heart failure.
AB  - Left ventricular (LV) ejection fraction (EF) was known as a conventional
      predictor of heart failure (HF). However, early transmitral flow velocity
      (E)/early diastolic velocity of mitral annulus (E') correlated well with LV end
      diastolic pressure, and E/E' ratio >15 was an excellent predictor of adverse
      outcomes in patients with HF. This study was designed to determine the prognostic
      value of a new combined index, E/E' ratio and LVEF, in patients with HF. One
      hundred twenty-six consecutive patients hospitalized with HF underwent
      comprehensive echocardiographic-Doppler study when ready for discharge. Patients
      were divided into the 4 groups of group I (LVEF >40% and E/E' ratio <15), group
      II (EF >40% and E/E' ratio >or=15), group III (EF <or=40% and E/E' ratio <15),
      and group IV (EF <or=40% and E/E' ratio >or=15). The ability of this index to
      determine the primary end point (rehospitalization for HF or cardiac death) was
      assessed. Patients with significant valvular disease were excluded. Of 126
      patients, 110 met the inclusion criteria. Follow-up was complete for 108 of 110
      patients at 351 +/- 252 days after discharge. There were 27, 30, 21, and 30
      patients in groups I, II, III, and IV, respectively. There were 52 patients with
      the primary end point. On univariate analysis, E/E' ratio, group IV, E', and age
      were significant predictors. In multivariable analysis, the most powerful
      independent prognostic indicator of events was group IV (hazard ratio 12.6, 95%
      confidence interval 2.2 to 74.2, p = 0.005). In conclusion, a new index, a
      combination of LVEF and E/E' ratio, allowed the identification of patients at
      higher risk of readmission and cardiac death in patients with HF.

PMID- 19406272
TI  - Effect of long-term resynchronization therapy on left ventricular remodeling in
      pacemaker patients upgraded to biventricular devices.
AB  - Right ventricular pacing resulted in abnormal ventricular depolarization and an
      activation pattern similar to left branch bundle block. In some circumstances, it
      may exacerbate symptoms of heart failure and increase hospital admission rates.
      The objective of this study was to assess the effects of long-term ventricular
      resynchronization therapy on echocardiographic parameters of left ventricular
      (LV) remodeling in patients with moderate to severe heart failure who were
      upgraded from single- to biventricular pacing. Twenty-six consecutive pacemaker
      dependent patients (20 men; mean age 61 +/- 20 years) who underwent placement of
      an LV lead to upgrade their conventional pacing system to biventricular pacing
      were included in the study. All patients had heart failure symptoms, received the
      maximum tolerated medical therapy, and were stable for >or=1 month before the
      upgrade. Echocardiography and electrocardiography were performed before the
      pacemaker upgrade and at follow-up (mean duration 15 +/- 9 months). QRS duration
      decreased significantly from 176 +/- 23 to 154 +/- 19 ms (p <0.001). LV end
      diastolic volume (p = 0.006) and LV end-systolic volume (p = 0.004) decreased at
      follow-up compared with baseline. The decrease in LV volumes observed during
      follow-up was accompanied by a significant increase in ejection fraction (39 +/-
      11% to 46 +/- 10%; p = 0.001) and decrease in LV myocardial performance index
      (0.84 +/- 0.18 to 0.68 +/- 0.14; p = 0.001). The upgrade of conventional pacing
      to biventricular pacing resulted in significant prolongation of normalized LV
      filling time (p = 0.01) and shortening of isovolumic contraction time (p 0.002).
      In addition, biventricular pacing significantly (V-V interval = 0) reduced intra-
      (44 +/- 11 vs 18 +/- 12 ms; p <0.001) and interventricular dyssynchrony (78 +/-
      33 vs 49 +/- 22 ms; p <0.001). In conclusion, these findings suggested that in
      patients with advanced heart failure and continuous right ventricular pacing,
      upgrading to biventricular system resulted in significant reverse LV remodeling
      in the long-term follow-up and improvement in overall synchronicity of
      ventricular function.

PMID- 19406270
TI  - Usefulness of myeloperoxidase levels in healthy elderly subjects to predict risk
      of developing heart failure.
AB  - Increased systemic myeloperoxidase (MPO) has been associated with both the
      presence and severity of heart failure (HF). This study tested the hypothesis
      that increased systemic MPO in apparently healthy elderly subjects may predict
      increased risk of developing HF. Systemic MPO was measured in all available
      samples from the 1992 to 1993 visit of the Cardiovascular Health Study (CHS).
      After excluding subjects without available blood samples or with a history of
      prevalent HF, myocardial infarction (MI), or stroke, 3,733 subjects were
      included. A total of 569 subjects developed incident HF during 7.2 +/- 2.3 years
      of follow-up. Patients in the highest MPO quartile (>432 pmol/L) showed higher
      risk of developing incident HF after adjusting for MI, age, gender, systolic
      blood pressure, smoking, low-density lipoprotein cholesterol, diabetes mellitus,
      and any subclinical cardiovascular disease (hazard ratio 1.34, 95% confidence
      interval 1.06 to 1.72, p = 0.013). However, the relation was more apparent after
      censoring subjects with incident MI before incident HF, even when adjusted for C
      reactive protein and cystatin C (hazard ratio 1.46, 95% confidence interval 1.08
      to 1.97, p = 0.02). Interestingly, stratified analyses showed that the relation
      between increased MPO and HF risk was stronger in subjects without traditional
      cardiovascular risk factors (<or=75 years old, systolic blood pressure <or=136 mm
      Hg, no subclinical cardiovascular disease, and no diabetes mellitus). In
      conclusion, an independent association between increased MPO and the development
      of HF in apparently healthy elderly subjects was observed, particularly beyond MI
      and traditional cardiac risk factors.

PMID- 19406273
TI  - Relation of depression to severity of illness in heart failure (from Heart
      Failure And a Controlled Trial Investigating Outcomes of Exercise Training [HF
      ACTION]).
AB  - Depression is common in patients with heart failure (HF), prognostic for adverse
      outcomes and purportedly related to disease severity. Psychological and
      physiologic factors relevant to HF were assessed in HF-ACTION, a large randomized
      study of aerobic exercise training in patients with systolic HF. The relation of
      objective and subjective parameters was compared with scores on the Beck
      Depression Inventory (BDI) to examine the hypothesis that depressive symptoms are
      better associated with perception of disease severity than with objective markers
      of HF severity. At baseline, 2,322 of 2,331 subjects entered into HF-ACTION
      completed questionnaires to assess depression (BDI) and quality of life (Kansas
      City Cardiomyopathy Questionnaire [KCCQ]). Objective markers of HF severity
      included ejection fraction, B-type natriuretic peptide, and peak oxygen
      consumption (using cardiopulmonary exercise testing, with evaluation of duration
      and respiratory exchange ratio also performed). Measures more likely to be
      affected by perceived functional status included New York Heart Association
      (NYHA) classification and the 6-minute walk test. Objective assessments of
      disease severity were slightly related (peak oxygen consumption) or not related
      (B-type natriuretic peptide and ejection fraction) to BDI scores. Using
      multivariate analysis (KCCQ not included), only age, gender, cardiopulmonary
      exercise testing duration, NYHA class, 6-minute walk distance, and peak
      respiratory exchange ratio independently correlated with BDI scores. In
      conclusion, depression was minimally related to objective assessments of severity
      of disease in patients with HF, but was associated with patient (and clinician)
      perceptions of disease severity. Addressing depression might improve symptoms in
      patients with HF.

PMID- 19406274
TI  - Usefulness of heart rate as an independent predictor for survival after heart
      transplantation.
AB  - It was unclear whether increased heart rate (HR) increased long-term mortality
      after heart transplantation (HT). The aim of this study was to evaluate whether
      HR predicted survival after HT. A retrospective analysis of patients who
      underwent HT at our institution was performed. Ethnicity, gender, date of birth,
      age at transplantation, length of follow-up after transplantation, cardiac rhythm
      within 3 months after transplantation, age at death, reason for transplantation,
      cause of death, and baseline medications after transplantation were recorded.
      Continuous variables, such as HR, blood pressure, cardiac ejection fraction,
      presence of allograft vasculopathy, and serum creatinine, were recorded at <3
      months, 6 months, and 1 year after HT, then annually to 10 years after HT.
      Seventy-eight patients with a mean age of 50 +/- 13 years were identified. Mean
      survival was 8.5 +/- 6.5 years. Of 78 patients, 32 patients had an HR <or=90
      beats/min, and 46 patients had an HR >90 beats/min within 3 months after HT.
      There was a mean decrease in HR of 6 beats/min during 10 years (p <0.03).
      Multivariate survival analysis showed that HR >90 beats/min was a significant
      predictor of early mortality (hazard ratio 2.8, 95% confidence interval 1.5 to
      5.1, p <0.0013). Patients with a net increase in HR during 10 years had an
      increased risk of death compared with patients with no change or a net decrease
      in HR (hazard ratio 4.7, 95% confidence interval 1.9 to 12.0, p <0.002). No
      significant differences in cause of death between patients with an HR <or=90 or
      >90 beats/min existed. In conclusion, HT patients with an HR >90 beats/min within
      the first 3 months after HT were 2.8 times more likely to die than patients with
      an HR <or=90 beats/min. Patients with a net increase in HR were 4.7 times more
      likely to die than those whose HR did not change or decreased over time.

PMID- 19406275
TI  - Role of multislice computed tomography in transcatheter aortic valve replacement.
AB  - Transcatheter aortic valve replacement (TAVR) required precise knowledge of the
      anatomic dimensions and physical characteristics of the aortic valve, annulus,
      and aortic root. Most groups currently use angiography, transthoracic
      echocardiography (TTE), or transesophageal echocardiography (TEE) to assess
      aortic annulus dimensions and anatomy. However, multislice computed tomography
      (MSCT) may allow more detailed 3-dimensional assessment of the aortic root.
      Twenty-six patients referred for TAVR underwent MSCT. Scans were also obtained
      for 18 patients after TAVR. All patients underwent pre- and postprocedural aortic
      root angiography, TTE, and TEE. Mean differences in measured aortic annular
      diameters were 1.1 mm (95% confidence interval 0.5, 1.8) for calibrated
      angiography and TTE, -0.9 mm (95% confidence interval -1.7, -0.1 mm) for TTE and
      TEE, -0.3 mm (95% confidence interval -1.1, 0.6 mm) for MSCT (sagittal) and TTE,
      and -1.2 mm (95% confidence interval -2.2, -0.2 mm) for MSCT (sagittal) and TEE.
      Coronal systolic measurements using MSCT, which corresponded to angiographic
      orientation, were 3.2 mm (1st and 3rd quartiles 2.6, 3.9) larger than sagittal
      systolic measurements, which were in the same anatomic plane as standard TTE and
      TEE views. There was no significant association between either shape of the
      aortic annulus or amount of aortic valve calcium and development of perivalvular
      aortic regurgitation. After TAVR, the prosthesis extended to or beyond the
      inferior border of the left main ostium in 9 of 18 patients (50%), and in 11
      patients (61%), valvular calcium was <5 mm from the left main ostium. In
      conclusion, MSCT identified that the aortic annulus was commonly eccentric and
      often oval. This may in part explain the small, but clinically insignificant,
      differences in measured aortic annular diameters with other imaging modalities.
      MSCT after TAVR showed close proximity of both the prosthesis and displaced
      valvular calcium to the left main ostium in most patients. Neither eccentricity
      nor calcific deposits appeared to contribute significantly to severity of
      paravalvular regurgitation after TAVR.

PMID- 19406276
TI  - Electrocardiographic pattern in arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiac disease
      characterized by progressive myocardial atrophy and fibrofatty replacement.
      Standard electrocardiograms (ECGs) and signal-averaged ECGs (SAECGs) were
      relatively low cost and repeatable diagnostic tools. In this study, ECGs and
      SAECGs of patients with ARVC were analyzed with the aim to assess the diagnostic
      capability of these noninvasive techniques. A total of 205 patients with ARVC
      were analyzed. ECGs were abnormal in 74% of patients and SAECGs were positive in
      60%, with normal ECGs mostly related to mild forms of the disease. The most
      common electrocardiographic abnormalities were localized right QRS prolongation,
      poor r wave progression in the right precordial leads, incomplete right branch
      bundle block, prolonged S-wave upstroke in V(1) to V(3), parietal block, ST
      segment elevation in V(1) to V(3), inversion of T waves beyond V(2), and epsilon
      wave. Low QRS voltages in the precordial leads were frequently present in all
      patients with ARVC compared with a group of 120 healthy subjects (p = 0.00001). T
      wave inversion beyond V(3) characterized subjects with severe right ventricular
      dilatation, whereas in subjects with left ventricular involvement, T-wave
      inversion in lateral leads was more commonly detected. Overall, the extent of
      electrocardiographic abnormalities was related to disease extent. In conclusion,
      abnormalities in ECGs and SAECGs were frequent in patients with ARVC and
      correlated with disease extent, even if a stereotypical electrocardiographic
      pattern did not exist. ECGs and SAECGs remain an important tool for the diagnosis
      and assessment of ARVC extent. Nonetheless, a normal ECG does not exclude the
      presence of the disease.

PMID- 19406277
TI  - Effect of bosentan on exercise capacity and quality of life in adults with
      pulmonary arterial hypertension associated with congenital heart disease with and
      without Down's syndrome.
AB  - Pulmonary arterial hypertension associated with congenital heart disease caused
      by systemic-to-pulmonary shunting was associated with a high risk of morbidity
      and mortality. In this retrospective study, the longer term treatment effect of
      bosentan on exercise capacity and quality of life (QoL) were evaluated in 58
      adult patients (>18 years) with pulmonary arterial hypertension associated with
      congenital heart disease, including patients with Down's syndrome. All patients
      were evaluated at baseline and during follow-up using laboratory tests, 6-minute
      walk test, QoL questionnaires, and Doppler echocardiography. Treatment efficacy
      was analyzed separately for patients without (n = 30) and with Down's syndrome (n
      = 28). Median follow-up of all patients treated with bosentan was 22 months
      (range 3 to 36). In patients without Down's syndrome, mean 6-minute walk distance
      increased from 427 +/- 97 to 461 +/- 104 m (p <0.01) after 6 months of treatment,
      followed by a gradual return to baseline and disease stabilization. QoL improved
      significantly during treatment and was maintained during 18 months of follow-up
      (p <0.05). In patients with Down's syndrome, 6-minute walk distance and QoL were
      stable during treatment. In conclusion, findings suggested that in patients
      without Down's syndrome, longer term bosentan treatment resulted in a persistent
      improvement in QoL and stabilization of exercise capacity.

PMID- 19406278
TI  - Clinical and research applications of carotid intima-media thickness.
AB  - Cardiovascular imaging modalities such as coronary computed tomography, carotid
      ultrasonography, and cardiovascular magnetic resonance imaging are increasingly
      being used to measure cardiovascular disease progression. Imaging measures, most
      notably carotid intima-media thickness (CIMT), are being applied as surrogate
      markers for clinical end points such as myocardial infarction and death in
      clinical trials. Clinicians and their patients are faced with the challenge of
      evaluating these imaging measures for their efficacy and practicality in clinical
      practice, as well as in clinical trials. The investigators determined from a
      review of clinical trials and guidelines that CIMT measurement may be useful in
      evaluating cardiovascular disease risk in select patient populations but may not
      always be an appropriate surrogate for clinical end points. In conclusion,
      although CIMT has clear advantages over alternative cardiovascular imaging
      modalities, ultimately, prospective trials comparing the effectiveness of CIMT as
      a predictive tool of cardiovascular risk with that of other novel markers would
      best direct clinical recommendations for this imaging measure.

PMID- 19406279
TI  - Utility of ezetimibe.

PMID- 19406280
TI  - The extrapolation of study results in the device approval process.

PMID- 19406281
TI  - Evaluating lipid-lowering trials in the twenty-first century.

PMID- 19406282
TI  - Proper testing for myocardial ischemia in firefighters.

PMID- 19406283
TI  - Prognostic values of various markers in evaluation of patients with chest pain.

PMID- 19406284
TI  - Arterial age as a function of coronary artery calcium.

PMID- 19406285
TI  - In ST-Elevation myocardial infarction patients receiving primary percutaneous
      coronary intervention, admission cardiac troponin T and peak cardiac troponin T
      values differ in their prognostic properties.

PMID- 19406286
TI  - Beta-blocker use and the development of depression.

PMID- 19406287
TI  - The clinical dilemma of positive results of high-sensitive troponin assays.

PMID- 19406289
TI  - Lower thoracic spinal cord stimulation to restore cough in patients with spinal
      cord injury: results of a National Institutes of Health-sponsored clinical trial.
      Part I: methodology and effectiveness of expiratory muscle activation.
AB  - OBJECTIVE: Evaluation of the capacity of lower thoracic spinal cord stimulation
      (SCS) to activate the expiratory muscles and generate large airway pressures and
      high peak airflows characteristic of cough, in subjects with tetraplegia. DESIGN:
      Clinical trial. SETTING: Inpatient hospital setting for electrode insertion;
      outpatient setting for measurement of respiratory pressures; home setting for
      application of SCS. PARTICIPANTS: Subjects (N=9; 8 men, 1 woman) with cervical
      spinal cord injury and weak cough. INTERVENTIONS: A fully implantable electrical
      stimulation system was surgically placed in each subject. Partial
      hemilaminectomies were made to place single-disk electrodes in the epidural space
      at the T9, T11, and L1 spinal levels. A radiofrequency receiver was placed in a
      subcutaneous pocket over the anterior portion of the chest wall. Electrode wires
      were tunneled subcutaneously and connected to the receiver. Stimulation was
      applied by activating a small portable external stimulus controller box powered
      by a rechargeable battery to each electrode lead alone and in combination. MAIN
      OUTCOME MEASURES: Peak airflow and airway pressure generation achieved with SCS.
      RESULTS: Supramaximal SCS resulted in high peak airflow rates and large airway
      pressures during stimulation at each electrode lead. Maximum peak airflow rates
      and airway pressures were achieved with combined stimulation of any 2 leads. At
      total lung capacity, mean maximum peak airflow rates and airway pressure
      generation were 8.6+/-1.8 (mean +/- SE) L/s and 137+/-30 cmH2O (mean +/- SE),
      respectively. CONCLUSIONS: Lower thoracic SCS results in near maximum activation
      of the expiratory muscles and the generation of high peak airflow rates and
      positive airway pressures in the range of those observed with maximum cough
      efforts in healthy persons.

PMID- 19406291
TI  - A randomized controlled trial of sertraline for the treatment of depression in
      persons with traumatic brain injury.
AB  - OBJECTIVE: To examine the efficacy of sertraline in the treatment of depression
      after traumatic brain injury (TBI). DESIGN: Double-blind, randomized controlled
      trial. SETTING: Research center at a major urban medical center. PARTICIPANTS:
      Subjects were a referred and volunteer sample of 52 participants with TBI, a
      diagnosis of major depression disorder (MDD), and a score on the Hamilton Rating
      Scale for Depression (HAM-D) of 18 or greater. The majority of the sample was
      male (58%), had less than 14 years of education (73%), had incomes below $20,000
      (82%), and were from minority backgrounds (75%). Approximately one third of the
      sample had mild brain injuries, and two thirds had moderate to severe brain
      injuries. The mean age was 47+/-11, and the mean time since injury was 17+/-14
      years. One participant withdrew from the study because of side effects.
      INTERVENTION: Daily oral sertraline in doses starting at 25mg and increasing to
      therapeutic levels (up to 200mg) or placebo for 10 weeks. MAIN OUTCOME MEASURES:
      The HAM-D, the Beck Anxiety Inventory, and the Life-3 quality of life (QOL).
      RESULTS: No statistically significant differences were found at baseline between
      drug and placebo groups on baseline measures of depression (24.8+/-7.3 vs 27.7+/
      7.0), anxiety (16.4+/-12.3 vs 24.0+/-14.9), or QOL (2.96+/-1.0 vs 2.9+/-0.9). The
      income level of those receiving placebo was significantly lower than those
      participants receiving medication. Analyses of covariance revealed significant
      changes from preintervention to posttreatment for all 3 outcome measures (P<.001)
      but no group effects. Random-effects modeling did not find any significant
      difference in patterns of scores of the outcome measures between the placebo and
      medication groups. CONCLUSIONS: Both groups showed improvements in mood, anxiety,
      and QOL, with 59% of the experimental group and 32% of the placebo group
      responding to the treatment, defined as a reduction of a person's HAM-D score by
      50%.

PMID- 19406292
TI  - Accuracy of manual needle placement for gastrocnemius muscle in children with
      cerebral palsy checked against ultrasonography.
AB  - OBJECTIVE: To investigate the accuracy of manual needle placement into
      gastrocnemius muscle (GCM) for botulinum toxin type A (BTX-A) injection in
      children with spastic cerebral palsy (CP). DESIGN: Prospective clinical study.
      SETTING: University-affiliated hospital. PARTICIPANTS: A total of 272 injections
      in GCMs of 39 children with spastic CP who were scheduled to receive BTX-A
      injections in GCMs. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The
      accuracy of manual needle placement was checked against ultrasonography. RESULTS:
      The needle was accurately inserted into GCM muscles in 78.7% of cases. Accuracy
      was 92.6% into gastrocnemius medialis (GM) and 64.7% into gastrocnemuis lateralis
      (GL). Muscle thickness at the needle insertion site was significantly thinner in
      GL than GM. Accuracy of GL in the younger age group (<4y, 57.6%) was lower than
      in the older age group (> or =4y, 78.1%). For GM, accuracy in both younger and
      older age groups was good (>90%). CONCLUSIONS: Injection of the toxin into GCMs
      through the use of anatomic landmark was acceptable in GM, but not acceptable in
      GL, especially in young children.

PMID- 19406290
TI  - Lower thoracic spinal cord stimulation to restore cough in patients with spinal
      cord injury: results of a National Institutes of Health-Sponsored clinical trial.
      Part II: clinical outcomes.
AB  - OBJECTIVE: To evaluate the clinical effects of spinal cord stimulation (SCS) to
      restore cough in subjects with cervical spinal cord injury. DESIGN: Clinical
      trial assessing the clinical outcomes and side effects associated with the cough
      system. SETTING: Outpatient hospital or residence. PARTICIPANTS: Subjects (N=9; 8
      men, 1 woman) with cervical spinal cord injury. INTERVENTIONS: SCS was performed
      at home by either the subjects themselves or caregivers on a chronic basis and as
      needed for secretion management. MAIN OUTCOME MEASURES: Ease in raising
      secretions, requirement for trained caregiver support related to secretion
      management, and incidence of acute respiratory tract infections. RESULTS: The
      degree of difficulty in raising secretions improved markedly, and the need for
      alternative methods of secretion removal was virtually eliminated. Subject life
      quality related to respiratory care improved, with subjects reporting greater
      control of breathing problems and enhanced mobility. The incidence of acute
      respiratory tract infections fell from 2.0+/-0.5 to 0.7+/-0.4 events/subject year
      (P<.01), and mean level of trained caregiver support related to secretion
      management measured over a 2-week period decreased from 16.9+/-7.9 to 2.1+/-1.6
      and 0.4+/-0.3 times/wk (P<.01) at 28 and 40 weeks after implantation of the
      device, respectively. Three subjects developed mild hemodynamic effects that
      abated completely with continued SCS. Subjects experienced mild leg jerks during
      SCS, which were well tolerated. There were no instances of bowel or bladder
      leakage. CONCLUSIONS: Restoration of cough via SCS is safe and efficacious. This
      method improves life quality and has the potential to reduce the morbidity and
      mortality associated with recurrent respiratory tract infections in this patient
      population.

PMID- 19406293
TI  - A specific inpatient aquatic physiotherapy program improves strength after total
      hip or knee replacement surgery: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effect of inpatient aquatic physiotherapy in addition
      to usual ward physiotherapy on the recovery of strength, function, and gait speed
      after total hip or knee replacement surgery. DESIGN: Pragmatic randomized
      controlled trial with blinded 6-month follow-up. SETTING: Acute-care private
      hospital. PARTICIPANTS: People (n=65) undergoing primary hip or knee arthroplasty
      (average age, 69.6+/-8.2y; 30 men). INTERVENTIONS: Participants were randomly
      assigned to receive supplementary inpatient physiotherapy, beginning on day 4:
      aquatic physiotherapy, nonspecific water exercise, or additional ward
      physiotherapy. MAIN OUTCOME MEASURES: Strength, gait speed, and functional
      ability at day 14. RESULTS: At day 14, hip abductor strength was significantly
      greater after aquatic physiotherapy intervention than additional ward treatment
      (P=.001) or water exercise (P=.011). No other outcome measures were significantly
      different at any time point in the trial, but relative differences favored the
      aquatic physiotherapy intervention at day 14. No adverse events occurred with
      early aquatic intervention. CONCLUSIONS: A specific inpatient aquatic
      physiotherapy program has a positive effect on early recovery of hip strength
      after joint replacement surgery. Further studies are required to confirm these
      findings. Our research indicates that aquatic physiotherapy can be safely
      considered in this early postoperative phase.

PMID- 19406294
TI  - The ability of ultrasonography, magnetic resonance imaging and bone mineral
      densitometry to predict the strength of human Achilles' tendons.
AB  - OBJECTIVE: To assess the value of ultrasonography (US), magnetic resonance
      imaging (MRI), and bone mineral densitometry (BMD) in evaluating human Achilles'
      tendon strength. DESIGN: Cross-sectional observational study. SETTING: Tertiary
      care hospital. PARTICIPANTS: Ninety-eight Achilles' tendons from 49 consecutive
      cadavers (26 men and 23 women with a mean age of 66.6 years) undergoing hospital
      autopsy were assessed. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Tendon dimensions on US and MRI, and T1-weighted optical density were measured.
      Areas of hypodensity, hyperdensity, calcification, and heterogeneity were
      identified on US. The BMD of each calcaneus was recorded. The tendons were
      mechanically tested to determine peak load at failure. RESULTS: Sixteen patients
      (32.7%, 27 tendons) had abnormalities in 1 or both tendons on US and/or MRI (17
      on US, 17 on MRI). Fifty-seven tendons (58%) ruptured in their midsubstance, at
      an average peak load of 4722+/-990N. Tendons with and without abnormalities on
      imaging had similar strengths (P>.05). Calcaneal BMD correlated weakly with peak
      load at failure (r=.21, P<.05). CONCLUSIONS: The prevalence of Achilles' tendons
      abnormalities on US or MRI was 32.7% in our study group. Abnormalities on
      clinical imaging (US or MRI) were not predictive of the load at failure.
      Therefore, tendons with imaging abnormalities are not necessarily weaker, and one
      cannot predict the likelihood of rupture based on imaging results. Further,
      higher-powered studies could explore the ability of BMD to detect minimal
      clinically important differences and to predict Achilles' tendon weakness.

PMID- 19406295
TI  - Ultrasound characteristics of the deep abdominal muscles during the active
      straight leg raise test.
AB  - OBJECTIVE: To determine whether changes in the transversus abdominis (TrA) and
      internal oblique (IO) muscles, as seen on ultrasound imaging, during the active
      straight leg raise (ASLR) test differ between subjects with and without
      unilateral lumbopelvic pain. DESIGN: Cross-sectional, case-control study.
      SETTING: Clinical laboratory. PARTICIPANTS: Subjects (n=15) with unilateral
      symptoms in the lumbopelvic region and age-matched and sex-matched control
      subjects (n=15). INTERVENTIONS: Bilateral measurements of the deep abdominal
      muscles (TrA and IO) were obtained simultaneously using ultrasound imaging to
      compare the percent change in muscle thickness from rest with (1) immediately on
      raising, (2) after a 10-second hold, and (3) within 5 seconds after returning the
      lower extremity to the plinth. MAIN OUTCOME MEASURE: Percent change in muscle
      thickness of both muscles from rest to the other 3 time intervals during the ASLR
      test. RESULTS: The 3-way group x side measured x time and 2-way side measured x
      time interactions were not significant for either the TrA (P> or =.34) or the IO
      (P> or =.14) muscles. The 2-way interaction group x time was significant for both
      the TrA (P=.003) and the IO (P=.02) muscles. On lifting the lower extremity, the
      control group demonstrated a 23.7% and 11.2% increase in TrA and IO muscle
      thickness, respectively, while those with lumbopelvic pain demonstrated a 6.4%
      and 5.7% increase in TrA and IO muscle thickness, respectively. CONCLUSIONS:
      Although subjects with unilateral lumbopelvic pain demonstrated a smaller
      increase in muscle thickness, during the ASLR test there appears to be a
      symmetrical response in both of the deep abdominal muscles regardless of which
      lower extremity is lifted during the ASLR test or the unilateral nature of the
      symptoms. This study attests to the potential construct validity of using the
      ASLR test to assess different motor control strategies of the TrA and IO muscles
      in subjects with unilateral lumbopelvic pain.

PMID- 19406296
TI  - Clinical outcomes for patients classified by fear-avoidance beliefs and
      centralization phenomenon.
AB  - OBJECTIVES: To (1) determine the prevalence of pain pattern classification
      subgroups (centralization, noncentralization, and not classified) observed during
      the initial evaluation of patients experiencing high versus low Fear-Avoidance
      Beliefs Questionnaire for physical activity (FABQ-PA) scores, (2) examine the
      association between discharge pain intensity and functional status (FS) outcomes
      based on FABQ-PA and pain pattern subgroups, and (3) compare minimal clinically
      important improvement for FS and pain intensity for FABQ-PA and pain pattern
      classification subgroups. DESIGN: Observational cohort design. SETTING: Suburban
      hospital-based outpatient rehabilitation clinic. PARTICIPANTS: Consecutive
      patients with low back syndromes (N=238, mean +/- SD, 59.1+/-17.0y; minimum=20,
      maximum=91). INTERVENTIONS: Interventions were designed to match patient
      classification by fear-avoidance level and pain pattern. MAIN OUTCOME MEASURES:
      Two outcome measures were assessed: patient self-reported FS and pain intensity.
      FS was assessed by using computerized adaptive testing methods. Maximal pain
      intensity was assessed by using an 11-point numeric pain scale: 0 (no pain) to 10
      (worst imaginable pain). RESULTS: There were no differences (chi(2)(2)=3.7,
      P=.16) in proportion of patients classified by pain pattern experiencing high or
      low fear-avoidance beliefs. After controlling for the effect of available risk
      adjustment variables, only dual-level classification subgroups, symptom acuity,
      payer type, and intake FS or pain intensity were associated with discharge FS or
      pain outcomes. The highest proportion of patients achieving minimal clinically
      important improvement in pain and FS were reported by the following patient
      subgroup: centralization and low fear. CONCLUSIONS: Pain pattern and FABQ-PA
      characteristics impacted rehabilitation outcomes. We recommend that both factors
      be considered when managing patients with low back pain in an effort to optimize
      rehabilitation outcomes.

PMID- 19406297
TI  - Patients with chronic disabling occupational musculoskeletal disorder failing to
      complete functional restoration: analysis of treatment-resistant personality
      characteristics.
AB  - OBJECTIVE: To identify the risk factors for noncompletion of a functional
      restoration program for patients with chronic disabling occupational
      musculoskeletal disorders. DESIGN: Prospective cohort study. SETTING: Consecutive
      patients undergoing functional restoration treatment in a regional rehabilitation
      referral center. PARTICIPANTS: A sample of 3052 consecutive patients, classified
      as either completers (n=2367) or noncompleters (n=685), who entered a functional
      restoration program. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The
      measures used included medical evaluations, demographic data, Diagnostic and
      Statistical Manual of Mental Disorders psychiatric diagnoses, the Minnesota
      Multiphasic Personality Inventory, and validated questionnaires evaluating pain,
      depression, and occupational factors. RESULTS: The findings revealed that
      patients who did not complete the program had a longer duration of total
      disability between injury and admission to treatment (completers=20mo vs
      noncompleters=13mo; P<.001). Furthermore, patients who were opioid-dependent were
      1.5 times more likely to drop out of rehabilitation, and patients diagnosed with
      a socially problematic Cluster B Personality Disorder were 1.6 times more likely
      to drop out. CONCLUSIONS: Although some risk factors associated with program
      noncompletion may be addressed in treatment, socially maladaptive personality
      disorders, long-neglected disability, and chronic opioid dependence are the major
      barriers to successful treatment completion. The patients identified with
      personality disorders may display resistance to treatment and may be difficult
      for the treatment staff to deal with. Early recognition of these treatment
      resistant personality characteristics in the functional restoration process may
      assist the treatment team in developing more effective strategies to help this
      dysfunctional group.

PMID- 19406299
TI  - Kinematics of pointing movements made in a virtual versus a physical 3
      dimensional environment in healthy and stroke subjects.
AB  - OBJECTIVE: To compare kinematics of 3-dimensional pointing movements performed in
      a virtual environment (VE) displayed through a head-mounted display with those
      made in a physical environment. DESIGN: Observational study of movement in
      poststroke and healthy subjects. SETTING: Motion analysis laboratory.
      PARTICIPANTS: Adults (n=15; 4 women; 59+/-15.4y) with chronic poststroke
      hemiparesis were recruited. Participants had moderate upper-limb impairment with
      Chedoke-McMaster Arm Scores ranging from 3 to 6 out of 7. Twelve healthy subjects
      (6 women; 53.3+/-17.1y) were recruited from the community. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Arm and trunk kinematics were recorded in
      similar virtual and physical environments with an Optotrak System (6 markers;
      100Hz; 5s). Subjects pointed as quickly and as accurately as possible to 6
      targets (12 trials/target in a randomized sequence) placed in arm workspace areas
      requiring different arm movement patterns and levels of difficulty. Movements
      were analyzed in terms of performance outcome measures (endpoint precision,
      trajectory, peak velocity) and arm and trunk movement patterns (elbow and
      shoulder ranges of motion, elbow/shoulder coordination, trunk displacement,
      rotation). RESULTS: For healthy subjects, precision and trajectory straightness
      were higher in VE when pointing to contralateral targets, and movements were
      slower for all targets in VE. Stroke participants made less accurate and more
      curved movements in VE and used less trunk displacement. Elbow/shoulder
      coordination differed when pointing to the lower ipsilateral target. There were
      no group-by-environment interactions. CONCLUSIONS: Movements in both environments
      were sufficiently similar to consider VE a valid environment for clinical
      interventions and motor control studies.

PMID- 19406298
TI  - Self-report of missteps in older adults: a valid proxy of fall risk?
AB  - OBJECTIVE: To evaluate the relationship between missteps and falls and to
      identify factors associated with missteps, potentially to generate a broader
      picture of fall risk. DESIGN: Prospective, observational cohort. SETTING: General
      community. PARTICIPANTS: A sample of healthy, community-living older adults
      (N=266; age, 70-90y) who were cognitively intact and walked independently.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Baseline testing of gait,
      motor function, cognitive function, affect, and balance confidence was followed
      by a 12-month period in which subjects completed a daily log documenting the
      number of falls and missteps (defined as a trip, slip, or other loss of balance
      in which recovery occurred to prevent a fall). RESULTS: Mean +/- SD participant
      age was 76.4+/-4.3 years. Of all the participants, 20.7% reported at least 1
      misstep, and 25.6% of the participants reported at least 1 fall during the 12
      months. Among subjects who had multiple falls, missteps were more common than
      falls by a ratio of 3:1 (P<.001). Subjects who reported multiple missteps were
      more likely to fall prospectively (relative risk=3.89). Missteps were associated
      with higher scores on the Geriatric Depression Scale (P=.009) and increased
      anxiety (P=.014), but were not associated with other known risk factors for
      falls, including gait and cognitive function. CONCLUSIONS: The self-report of
      missteps may be a valuable tool in the research of falls and fall risk and may
      provide a way to identify patients at risk for falls before they fall.

PMID- 19406300
TI  - Validity for the simplified water displacement instrument to measure arm
      lymphedema as a result of breast cancer surgery.
AB  - OBJECTIVES: To evaluate concurrent and construct validity for the Simplified
      Water Displacement Instrument (SWDI), an instrument for measuring arm volumes and
      arm lymphedema as a result of breast cancer surgery. DESIGN: Validity design.
      SETTING: Hospital setting. PARTICIPANTS: Women (N=23; mean age, 64+/-11y) were
      examined 6 years after breast cancer surgery with axillary node dissection.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The SWDI was included for
      measuring arm volumes to estimate arm lymphedema as a result of breast cancer
      surgery. A computed tomography (CT) scan was included to examine the cross
      sectional areas (CSAs) in square millimeters for the subcutaneous tissue, for the
      muscle tissue, and for measuring tissue density in Hounsfield units. Magnetic
      resonance imaging (MRI) with T2-weighted sequences was included to show increased
      signal intensity in subcutaneous and muscle tissue areas. RESULTS: The affected
      arm volume measured by the SWDI was significantly correlated to the total CSA of
      the affected upper limb (R=.904) and also to the CSA of the subcutaneous tissue
      and muscles tissue (R=.867 and R=.725), respectively (P<.001). The CSA of the
      subcutaneous tissue for the upper limb was significantly larger compared with the
      control limb (11%). Tissue density measured in Hounsfield units did not correlate
      significantly with arm volume (P>.05). The affected arm volume was significantly
      larger (5%) than the control arm volume (P<.05). Five (22%) women had arm
      lymphedema defined as a 10% increase in the affected arm volume compared with the
      control arm volume, and an increased signal intensity was identified in all 5
      women on MRI (T2-weighted, kappa=.777, P<.001). CONCLUSIONS: The SWDI showed high
      concurrent and construct validity as shown with significant correlations between
      the CSA (CT) of the subcutaneous and muscle areas of the affected limb and the
      affected arm volume (P>.001). There was a high agreement between those subjects
      who were diagnosed with arm lymphedema by using the SWDI and the increased signal
      intensity on MRI, with a kappa value of .777 (P<.001). High construct validity
      for the SWDI was confirmed for arm lymphedema as a volume increase, but it was
      not confirmed for lymphedema without an increase in arm volume (swelling). The
      SWDI is a simple and valid tool for estimating arm volume and arm lymphedema
      after breast cancer surgery.

PMID- 19406301
TI  - Effect of ankle-foot orthosis alignment and foot-plate length on the gait of
      adults with poststroke hemiplegia.
AB  - OBJECTIVE: To investigate the effect of ankle-foot orthosis (AFO) alignment and
      foot-plate length on sagittal plane knee kinematics and kinetics during gait in
      adults with poststroke hemiplegia. DESIGN: Repeated measures, quasi-experimental
      study. SETTING: Motion analysis laboratory. PARTICIPANTS: Volunteer sample of
      adults with poststroke hemiplegia (n=16) and able-bodied adults (n=12) of similar
      age. INTERVENTIONS: Subjects with hemiplegia were measured walking with
      standardized footwear in 4 conditions: (1) no AFO (shoes only); (2) articulated
      AFO with 90 degrees plantar flexion stop and full-length foot-plate
      conventionally aligned AFO (CAFO); (3) the same AFO realigned with the tibia
      vertical in the shoe-heel-height compensated AFO (HHCAFO); and (4) the same AFO
      (tibia vertical) with 3/4 length foot-plate-3/4 AFO. Gait of able-bodied control
      subjects was measured on a single occasion to provide a normal reference. MAIN
      OUTCOME MEASURES: Sagittal plane ankle and knee kinematics and kinetics. RESULTS:
      In adults with hemiplegia, walking speed was unaffected by the different
      conditions (P=.095). Compared with the no AFO condition, all AFOs decreased
      plantar flexion at initial contact and mid-swing (P<.001) and changed the peak
      knee moment in early stance from flexor to extensor (P<.000). Both AFOs with full
      length foot-plates significantly increased the peak stance phase plantar flexor
      moment compared with no AFO and resulted in a peak knee extensor moment in early
      stance that was significantly greater than control subjects, whereas the AFO with
      three-quarter length foot-plate resulted in ankle dorsiflexion during stance and
      swing that was significantly less than control subjects. CONCLUSIONS: These
      findings suggest that when an articulated AFO is to be used, a full-length foot
      plate in conjunction with a plantar flexion stop may be considered to improve
      early stance knee moments for people with poststroke hemiplegia.

PMID- 19406302
TI  - Changes in passive mechanical properties of the gastrocnemius muscle at the
      muscle fascicle and joint levels in stroke survivors.
AB  - OBJECTIVES: To investigate the ankle joint-level and muscle fascicle-level
      changes and their correlations in stroke survivors with spasticity, contracture,
      and/or muscle weakness at the ankle. DESIGN: To investigate the fascicular
      changes of the medial gastrocnemius muscle using ultrasonography and the
      biomechanical changes at the ankle joint across 0 degrees, 30 degrees, 60
      degrees, and 90 degrees knee flexion in a case-control manner. SETTING: Research
      laboratory in a rehabilitation hospital. PARTICIPANTS: Stroke survivors (n=10)
      with ankle spasticity/contracture and healthy control subjects (n=10).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASUREMENTS: At the muscle fascicle
      level, medial gastrocnemius muscle architecture including the fascicular length,
      pennation angle, and thickness were evaluated in vivo with the knee and ankle
      flexion changed systematically. At the joint level, the ankle range of motion
      (ROM) and stiffness were determined across the range of 0 degrees to 90 degrees
      knee flexion. RESULTS: At comparable joint positions, stroke survivors showed
      reduced muscle fascicle length, especially in ankle dorsiflexion (P< or =.048)
      and smaller pennation angle, especially for more extended knee positions (P< or
      =.049) than those of healthy control subjects. At comparable passive
      gastrocnemius force, stroke survivors showed higher fascicular stiffness (P< or
      =.044) and shorter fascicle length (P< or =.025) than controls. The fascicle
      level changes of decreased muscle fascicle length and pennation angle and
      increased medial gastrocnemius fascicle stiffness in stroke were correlated with
      the joint level changes of increased joint stiffness and decreased ROM (P<.05).
      CONCLUSIONS: This study evaluated specific muscle fascicular changes as
      mechanisms underlying spasticity, contracture, and joint-level impairments, which
      may help improve stroke rehabilitation and outcome evaluation.

PMID- 19406303
TI  - Dual energy x-ray absorptiometry of the distal femur may be more reliable than
      the proximal tibia in spinal cord injury.
AB  - OBJECTIVE: To evaluate the precision of dual energy x-ray absorptiometry scanning
      at 2 skeletal sites at the knee (proximal femur and distal tibia) in people with
      SCI. DESIGN: Cross-sectional. SETTING: Veterans Affairs Medical Center.
      PARTICIPANTS: Subjects (N=20) with chronic SCI. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Precision as determined by root mean square coefficient of
      variation (RMS-CV) and root mean square standard deviation (RMS-SD). RESULTS: At
      the distal femur the root RMS-CV was 3.01% and the RMS-SD was 0.025g/cm2. At the
      proximal tibia the RMS-CV was 5.91% and the RMS-SD was 0.030g/cm2. CONCLUSIONS:
      Precision at the distal femur is greater than at the proximal tibia and we
      recommend it as the preferred site for the longitudinal assessment of bone
      mineral density at the knee in chronic SCI.

PMID- 19406304
TI  - Transperineal injection of botulinum toxin A for treatment of detrusor sphincter
      dyssynergia: localization with combined fluoroscopic and electromyographic
      guidance.
AB  - OBJECTIVE: To determine the effectiveness of a combined method for localizing
      external urethral sphincter for transperineal injection of botulinum toxin A (BTX
      A) in the treatment of detrusor sphincter dyssynergia (DSD) in patients with
      spinal cord injury (SCI). DESIGN: A prospective, open-label trial. SETTING: A
      rehabilitation hospital affiliated with a medical university. PARTICIPANTS:
      Eighteen SCI patients with voiding dysfunction resulting from urodynamically
      confirmed DSD. INTERVENTIONS: 100 units of BTX-A injected transperineally into
      the external urethral sphincter, which was localized using combined fluoroscopic
      and electromyographic guidance, using a Foley catheter inserted for visualization
      of vesicourethral anatomy. MAIN OUTCOME MEASURES: (1) postvoid residual volume,
      (2) leak point pressure, (3) maximal intravesical pressure, (4) maximal urethral
      pressure, (5) quality of life measures for urination, quantified by the Quality
      of Life Index (QLI). RESULTS: Positive clinical outcomes were observed in all 18
      patients in this study. The mean reductions in postvoid residual volume, leak
      point pressure, maximal intravesical pressure, and maximal urethral pressure
      before and after BTX-A injection were 183ml, 37cm H2O, 45cm H2O, and 92cm H2O,
      respectively (all P values <.05). The mean QLI significantly improved from 
      0.68+/-0.27 to 0.66+/-0.19 (P<.01). No significant side effects were noted after
      injection. The clinical therapeutic effects have shown reductions in occurrence
      and degree of autonomic dysreflexia, vesicoureteral reflux, hydronephrosis, and
      urinary tract infection. The bladder management programs also obtained
      improvements in our patients, either doing intermittent catheterizations less
      frequently, or resuming spontaneous voiding without indwelling catheters.
      CONCLUSION: With this combined method for localization of the external urethral
      sphincter, transperineal injection of BTX-A was safe, accurate, easy to perform,
      and effective for treatment of DSD in patients with SCI.

PMID- 19406305
TI  - Pulmonary rehabilitation improves functional status in oncology patients.
AB  - OBJECTIVE: To determine if participation in a pulmonary rehabilitation (PR)
      program improved the functional and physiologic status of oncology patients with
      chronic symptoms of shortness of breath, fatigue, and/or exercise intolerance.
      DESIGN: Retrospective chart review. SETTING: Comprehensive cancer center.
      PATIENTS: Oncology patients (N=30) (either a solid or a hematologic malignancy)
      with chronic dyspnea, exercise intolerance, and/or decreased functional status
      who had participated in an outpatient PR program. INTERVENTIONS: The PR program
      used an individualized, progressive aerobic exercise program (2-3 sessions/wk for
      8-12 weeks) that consisted of treadmill walking, riding on a bicycle ergometer
      and exercising on a sliding board. This program also included a didactic
      educational and psychosocial component. MAIN OUTCOME MEASURES: Functional status
      and exercise tolerance was assessed by the 6-minute walk test (6MWT) conducted at
      the beginning and end of the program. Self reports of perceived exertion and
      dyspnea were collected during and after these tests. Physiologic status was
      assessed by calculating 6-minute walk work (body mass x 6-minute walk distance).
      RESULTS: Participation in the outpatient PR program significantly increased the 6
      minute walk distance (21%, P<.05) and 6-minute walk work (17%, P<.05). Dyspnea
      and perceived exertion scores were similar at the pre- and postrehabilitation
      6MWT despite the greater physiologic demand of the post-rehabilitation 6-minute
      walk. No adverse events occurred during the study. CONCLUSIONS: The current
      study, although limited in size, suggests that participation in a comprehensive
      outpatient PR program is safe and of benefit in a heterogeneous population of
      oncology patients with pulmonary symptoms.

PMID- 19406306
TI  - Alcohol misuse and multiple sclerosis.
AB  - OBJECTIVE: To describe the prevalence of alcohol misuse and medical advice to
      reduce drinking in a national sample of veterans with multiple sclerosis (MS).
      DESIGN: Cross-sectional cohort study linking computerized medical record
      information to mailed survey data from 2004 through 2006. SETTING: Veterans
      Health Administration (VHA). PARTICIPANTS: Two thousand six hundred fifty-five of
      4929 veterans with MS who received services in VHA between 2004 and 2006 and also
      a survey questionnaire (53.9% response rate). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Demographic information, Short-Form 12-Item Health Survey
      Mental Component Summary and Physical Component Summary, Alcohol Use Disorders
      Identification Test Consumption questions, and questions assessing depressive
      symptoms and the receipt of alcohol-related advice from a medical professional.
      RESULTS: Among all survey respondents with MS, the prevalence of alcohol misuse
      for the sample was 13.9% (confidence interval [CI], 12.5-15.2), with 11.9% (CI,
      10.6-13.2) and 2.0% (CI, 1.4-2.5) of participants scoring in the mild/moderate
      and severe range of alcohol misuse, respectively. In contrast to community
      samples there was no difference in prevalence by sex. In multivariate logistic
      regression, age younger than 60 years (<50y; adjusted odds ratio [AOR]=1.66; CI,
      1.17-2.37, and 50-59; AOR=1.64; CI, 1.19-2.27), employment (AOR=1.54; CI, 1.06
      2.24) and better physical health (AOR=1.02; CI, 1.01-1.04) were associated with a
      higher likelihood of alcohol misuse. Among persons who screened positive for
      alcohol misuse, only 26.2% (CI, 21.5-30.9) reported they had received advice from
      a medical provider in the past year to decrease or abstain from drinking. Self
      report of advice was more likely among those endorsing severe misuse (AOR=3.65;
      CI, 1.85-7.17) and less likely among those with better mental health (AOR=0.97;
      CI, 0.94-1.00). CONCLUSIONS: Despite the numerous health and social consequences
      of alcohol misuse, routine screening and intervention for people with MS remain
      uncommon. Brief screening and advice to reduce or refrain from alcohol use can be
      accomplished in as little as 5 minutes and can be incorporated into the regular
      course of medical care.

PMID- 19406307
TI  - Capacity, capability, and performance: different constructs or three of a kind?
AB  - OBJECTIVES: The present study focused on motor activities of young children with
      cerebral palsy (CP) and examined the relation between motor capacity (what a
      person can do in a standardized, controlled environment), motor capability (what
      a person can do in his/her daily environment), and motor performance (what a
      person actually does do in his/her daily environment). DESIGN: The relations
      between motor capacity, motor capability, and motor performance were calculated
      by using Pearson correlations and visualized by scatterplots. SETTING: A cross
      sectional study of a hospital-based population of children with CP. PARTICIPANTS:
      Subjects were children with CP (N=85) aged 30 months (Gross Motor Function
      Classification System levels I-V). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Motor capacity, motor capability, and motor performance were assessed
      with the Gross Motor Function Measure and 2 scales of the Pediatric Evaluation of
      Disability Inventory, respectively. RESULTS: Correlations between motor capacity,
      motor capability, and motor performance were high, between 0.84 and 0.92, and
      significant (P< .001). But when comparing children with the same level of motor
      capacity or motor capability, large ranges at the level of motor performance were
      found. CONCLUSIONS: Results imply that motor performance levels are only partly
      reflected by the motor capacity and motor capability levels in young children
      children with CP. Contextual factors (physical and social environment) and
      personal factors (such as motivation) influence the relations between capacity,
      capability, and performance. This information is essential in making decisions
      about the focus of therapy to maximize a child's independent functioning in daily
      life.

PMID- 19406308
TI  - Measuring participation as defined by the international classification of
      functioning, disability and health: an evaluation of existing measures.
AB  - OBJECTIVES: The content and theoretic underpinning of measures designed to assess
      participation, disability, and handicap vary widely, and few authors have
      attempted to compare the content of existing measures. The objectives of this
      study were to use the International Classification of Functioning, Disability and
      Health (ICF) taxonomy to (1) evaluate the participation content of measures and
      (2) identify the most comprehensive measures. DESIGN: We searched PubMed,
      Cumulated Index of Nursing and Allied Health Literature, and Health and
      Psychosocial Instruments databases to identify appropriate measures. Content
      analysis was conducted by classifying participation-related items of each measure
      into 1 or more of the 9 activities and participation chapters of the ICF
      taxonomy. SETTING: Not applicable. PARTICIPANTS: We evaluated 40 generic and
      condition-specific self-report measures that met study inclusion criteria.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The most comprehensive
      measures were identified and coded by using second- and third-level ICF codes.
      RESULTS: Five measures containing participation items linked to all 9 chapters
      were the Community Living Skills Scale, the Assessment of Life Habits, Mayo
      Portland Adaptability Inventory, the participation measure for postacute care,
      and the Psychosocial Adjustment to Illness Scale. The breadth and coverage of
      these 5 measures were compared. CONCLUSIONS: We identified 5 measures that had
      items that were linkable to all 9 chapters of activities and participation;
      however, these measures differed in specifics of coverage and the approach to
      assessing participation. These findings can be used by clinicians and researchers
      to select the most comprehensive participation outcome measure for their
      populations.

PMID- 19406309
TI  - Effects of modified pen grip and handwriting training on writer's cramp.
AB  - OBJECTIVE: To evaluate the use of a modified pen grip and subsequent handwriting
      training in patients with writer's cramp (WC). DESIGN: Handwriting performance
      with normal and modified pen grip was examined once in healthy controls and
      repeatedly in patients with WC (2 baseline tests before training, directly after
      training, after a 3-month follow-up). SETTING: Ambulatory care for motor writing
      disorders. PARTICIPANTS: Patients with WC (n=26) and healthy controls (n=14).
      INTERVENTION: Seven sessions of handwriting training with various motor exercises
      were conducted by an occupational therapist. During training, the patients always
      used a modified pen grip (stabilized between index and middle finger). MAIN
      OUTCOME MEASURES: Writing frequency and fluency, grip force on the pen, writing
      pressure, Fahn dystonia scale, visual analog scales for impairment and pain.
      RESULTS: Patients with WC showed increased writing pressure and grip force before
      training. Using the modified pen grip caused in both patients with WC and
      controls a decrease in pressure and grip force. Handwriting training resulted in
      a further improvement of both parameters in patients with WC. Grip force
      reduction remained stable over follow-up. CONCLUSIONS: Results suggest that
      patients with WC benefit from the use of the modified pen grip in combination
      with handwriting training.

PMID- 19406311
TI  - Leg edema with deep venous thrombosis-like symptoms as an unusual complication of
      occult bladder distension and right May-Thurner syndrome in a stroke patient: a
      case report.
AB  - Overt bladder distension can compress the iliac vessels and result in lower
      extremity swelling mimicking deep venous thrombosis (DVT). This phenomenon has
      been reported in patients with bladder outlet obstruction due to prostatism but
      no report has been made in relation to poststroke urinary retention (UR). The
      authors experienced a rare case of abrupt leg edema with DVT-like symptoms due to
      iliac vein compression by an overdistended bladder that had developed after
      cerebrovascular stroke. A 74-year-old woman with left striatocapsular infarction
      and situs inversus presented with severe right leg swelling. Imaging studies
      revealed external compression of the right iliac veins by an overdistended
      bladder and underlying May-Thurner syndrome (MTS). The presence of situs inversus
      totalis resulted in the rare clinical finding of a right-sided MTS. The patient's
      symptoms were largely attributable to external compression of right iliac veins
      by bladder distension and they resolved completely after prompt bladder drainage.
      Follow-up imaging findings showed complete regression of right external iliac
      vein stenosis. This case provides the first description of lower extremity
      swelling manifest as an unusual complication from UR in a stroke patient. Proper
      and strict bladder screening with appropriate management should be implemented as
      important therapeutic components during the rehabilitative management of stroke
      patients.

PMID- 19406312
TI  - The Urologic Clinics of North America. Preface.

PMID- 19406310
TI  - A systematic review of the management of orthostatic hypotension after spinal
      cord injury.
AB  - OBJECTIVE: To review systematically the evidence for the management of
      orthostatic hypotension (OH) in patients with spinal cord injuries (SCIs). DATA
      SOURCES: A key word literature search was conducted of original and review
      articles as well as practice guidelines using Medline, CINAHL, EMBASE, and
      PsycInfo, and manual searches of retrieved articles from 1950 to July 2008, to
      identify literature evaluating the effectiveness of currently used treatments for
      OH. STUDY SELECTION: Included randomized controlled trials (RCTs), prospective
      cohort studies, case-control studies, pre-post studies, and case reports that
      assessed pharmacologic and nonpharmacologic intervention for the management of OH
      in patients with SCI. DATA EXTRACTION: Two independent reviewers evaluated the
      quality of each study, using the Physiotherapy Evidence Database score for RCTs
      and the Downs and Black scale for all other studies. Study results were tabulated
      and levels of evidence assigned. DATA SYNTHESIS: A total of 8 pharmacologic and
      21 nonpharmacologic studies were identified that met the criteria. Of these 26
      studies (some include both pharmacologic and nonpharmacologic interventions),
      only 1 pharmacologic RCT was identified (low-quality RCT producing level 2
      evidence), in which midodrine was found to be effective in the management of OH
      after SCI. Functional electrical stimulation was one of the only nonpharmacologic
      interventions with some evidence (level 2) to support its utility. CONCLUSIONS:
      Although a wide array of physical and pharmacologic measures are recommended for
      the management of OH in the general population, very few have been evaluated for
      use in SCI. Further research needs to quantify the efficacy of treatment for OH
      in subjects with SCI, especially of the many other pharmacologic interventions
      that have been shown to be effective in non-SCI conditions.

PMID- 19406313
TI  - Image-fusion, augmented reality, and predictive surgical navigation.
AB  - Computer-aided surgical navigation systems with fusion or overlaying capability,
      coupled with newer position tracking systems, can provide new opportunities to
      improve the precision of minimally invasive urology. Three-dimensional feedback
      of spatial position of surgical targets, and the predictive ability to guide
      laparoscopic dissection along the ideal surgical plane, with built-in safety
      checks and balances may help to lay the foundation for automated surgery in the
      future.

PMID- 19406314
TI  - Molecular imaging in urologic surgery.
AB  - Recently, advances in imaging technology have made possible the ability to image
      noninvasively specific molecular pathways in vivo that are involved in disease
      processes. Molecular imaging evaluates changes in cellular physiology and
      function rather than anatomy, which are likely to be earlier and more sensitive
      manifestations of disease. In addition, as newer drugs to treat disease become
      increasingly molecule specific, molecular imaging has become necessary to provide
      noninvasive determination of patients likely to benefit from treatment and early
      therapy response. This article reviews current and emerging molecular imaging
      technologies relevant to urologic surgery.

PMID- 19406315
TI  - Advances in ultrasound technology in oncologic urology.
AB  - Continuous innovations and clinical research in ultrasound (US) technology have
      upgraded the position of US in the imaging armamentarium of urologists. In
      particular, contrast-enhanced US and sonoelastography seem to be promising in the
      diagnosis of urologic cancers, implementation of ablative treatments, and
      monitoring of treatment response. This article focuses on the potential clinical
      applications of recent advances in US technology in oncologic urology.

PMID- 19406316
TI  - Natural orifice translumenal endoscopic surgery.
AB  - This article presents a fair and balanced review of natural orifice translumenal
      endoscopic surgery. The article chronicles the history and technical aspects of
      natural orifice translumenal endoscopic surgery with particular emphasis on its
      application in urology. It is hoped that this article serves as a straightforward
      and pragmatic reference for practicing and academic urologists.

PMID- 19406317
TI  - Flexible robotics.
AB  - Robotic technology is being increasingly used for a variety of surgical
      procedures. This article describes some novel flexible robotic platforms that may
      enhance the capabilities of flexible endoscopy and provides a rationale for
      robotic technology's further development and future use. It also reviews some
      recent experimental and clinical usages of flexible robotic technology to perform
      ureterorenoscopy and to provide treatment of stones.

PMID- 19406318
TI  - Ablative technologies for urologic cancers.
AB  - Driven by patient preference and a more favorable oncologic prognosis at
      diagnosis, there has been a paradigm shift in the treatment of urologic cancers.
      Although the standard of care for most urologic malignancies continues to be
      surgical extirpation, ablation, in the form of needle-based or extracorporeal
      approaches, is quickly establishing itself as a viable primary treatment option.
      If there is anything to be learned from pioneering studies, it is that there must
      be strict adherence to inclusion criteria for patient enrollment and that there
      are real limitations with each approach. It is only with this awareness that we
      can achieve maximal benefit while limiting the number of unnecessary
      complications and poor oncologic outcomes.

PMID- 19406320
TI  - Advances in laser technology in urology.
AB  - Since the Ruby laser was first developed in 1960 as the first successful optical
      laser, laser energy has continued to be developed and used in industry and
      medicine alike. Laser use in urology has been limited, however, largely until the
      last decade. The unique properties of laser energy have now led to its widespread
      use within urology, particularly in the treatment of benign prostatic
      hyperplasia, urolithiasis, stricture disease, and novel laparoscopic
      applications. This article details laser developments in each of these areas.

PMID- 19406321
TI  - Regenerative medicine and tissue engineering in urology.
AB  - Tissue engineering efforts are currently being undertaken for every type of
      tissue and organ within the urinary system. Most of the effort expended to
      engineer genitourinary tissues has occurred within the past decade. Tissue
      engineering techniques require a cell culture facility designed for human
      application. Personnel who have mastered the techniques of cell harvest, culture,
      and expansion in addition to polymer design are essential for the successful
      application of this technology. Before these engineering techniques can be
      applied to humans, further studies need to be performed in many of the tissues
      described. Recent progress suggests that engineered urologic tissues and cell
      therapy may have clinical applicability.

PMID- 19406322
TI  - Intraoperative tissue characterization and imaging.
AB  - As surgical operative technology improves, surgeons today have the ability to
      visualize fine structures and detailed anatomy. There are a number of advances
      that have been made to optimize patient outcomes with better tissue
      characterization in urologic procedures. This article focuses on advances in
      intraoperative imaging and tissue characterization for various urologic
      procedures. Each modality is presented with its corresponding applications in
      urology. The following techniques are covered: optical coherence tomography,
      confocal fluorescent microscopy, near infrared fluorescence imaging,
      elastography, intraoperative ultrasonography, and a neurovascular bundle surgical
      mapping aid.

PMID- 19406319
TI  - Nanotechnology in urology.
AB  - Nanomedicine is a new distinct scientific discipline that explores applications
      of nanoscale materials for various biomedical applications. Translational
      nanomedicine is undergoing rapid transition from development and evaluation in
      laboratory animals to clinical practices. In the future, it is anticipated that
      nanotechnology can provide urologists a new point of view to understand the
      mechanism of disease, tools for early diagnosis of the disease, and effective
      modality for treatment. This article summarizes some of the emerging applications
      of nanomedicine in urology.

PMID- 19406323
TI  - Laparoendoscopic single site surgery in urology.
AB  - Laparoendoscopic single site (LESS) surgery is a recently coined term that refers
      to a group of techniques that perform laparoscopic intervention through a single
      abdominal incision often hidden within the umbilicus. The relative ease and
      swiftness of early success of LESS surgery is in large part because of the
      familiarity of current practitioners with advanced laparoscopic techniques and
      the advent of several technologic advances in the areas of instrumentation,
      camera systems, and access devices. As ongoing advancements in instrumentation
      and future robotics platforms are incorporated, the scope and application of LESS
      surgery is likely to expand. Ultimately, prospective studies that compare the
      safety and effectiveness of this new approach with the standard conventional
      laparoscopic approach will determine the future role in surgical practice.

PMID- 19406324
TI  - Technological advances in robotic-assisted laparoscopic surgery.
AB  - In this article, the authors describe the evolution of urologic robotic systems
      and the current state-of-the-art features and existing limitations of the da
      Vinci S HD System (Intuitive Surgical, Inc.). They then review promising
      innovations in scaling down the footprint of robotic platforms, the early
      experience with mobile miniaturized in vivo robots, advances in endoscopic
      navigation systems using augmented reality technologies and tracking devices, the
      emergence of technologies for robotic natural orifice transluminal endoscopic
      surgery and single-port surgery, advances in flexible robotics and haptics, the
      development of new virtual reality simulator training platforms compatible with
      the existing da Vinci system, and recent experiences with remote robotic surgery
      and telestration.

PMID- 19406325
TI  - Miniature in vivo robotics and novel robotic surgical platforms.
AB  - Robotic surgical systems, such as the da Vinci Surgical System (Intuitive
      Surgical, Inc., Sunnyvale, California), have revolutionized laparoscopic surgery
      but are limited by large size, increased costs, and limitations in imaging.
      Miniature in vivo robots are being developed that are inserted entirely into the
      peritoneal cavity for laparoscopic and natural orifice transluminal endoscopic
      surgical (NOTES) procedures. In the future, miniature camera robots and
      microrobots should be able to provide a mobile viewing platform. This article
      discusses the current state of miniature robotics and novel robotic surgical
      platforms and the development of future robotic technology for general surgery
      and urology.

PMID- 19406326
TI  - Advances in bioadhesives, tissue sealants, and hemostatic agents.
AB  - The use of bioadhesives, tissue sealants, and hemostatic agents has allowed for
      increased use of minimally invasive techniques for complex reconstructive
      urologic procedures. Hemostatic agents can facilitate clot formation through
      enzymatic reactions with host factors, mechanical compression, or a combination
      of the two. Tissue sealants and bioadhesives act through polymerization between
      themselves and adjacent tissues. This article reviews the unique features,
      mechanism of action, safety profile, and prototypical applications of the agents
      most commonly used in urologic surgery.

PMID- 19406331
TI  - Save lives: clean your hands. A global call for action at the point of care.

PMID- 19406332
TI  - Gram-negative bloodstream infections in hematopoietic stem cell transplant
      patients: the roles of needleless device use, bathing practices, and catheter
      care.
AB  - BACKGROUND: Between August 1 and October 30, 1998 (outbreak period), an increased
      incidence of central venous catheter (CVC)-associated gram-negative bacterial
      bloodstream infection (GN-BSI) was detected in hematopoietic stem cell
      transplantation (HSCT) candidates and recipients in an outpatient HSCT unit. The
      objectives of the present study were to determine strategies for controlling the
      outbreak and identify risk factors for GN-BSI. METHODS: Two case-control studies,
      an assessment of infection control practices, microbiologic studies, and water
      quality analysis were conducted. A case was defined as any outpatient with a CVC
      and a primary GN-BSI during the outbreak period. RESULTS: All of the 31 case
      patients identified had needleless intravenous (IV) access devices. Independent
      risk factors for CVC-associated GN-BSI were self-administered IV infusion (odds
      ratio [OR] = 6.2; P = .02), lower frequency of needleless device changes (OR =
      15.2; P = .03), and more frequent baths (OR = 1.4; P = .05). Interventions
      included increased frequency of needleless device change, recommending showers
      rather than baths, and use of CVC protection during showering/bathing. After
      these interventions, the CVC-associated GN-BSI rate declined to below the
      preoutbreak period rate (2.1/1000 vs 0.3/1000 CVC-days; P < .01). CONCLUSIONS:
      This study demonstrated an increased risk of CVC-associated GN-BSIs related to
      self-IV infusion, bathing habits, and frequency of needleless device change.
      Infection control practices associated with the use of needleless devices may
      expose susceptible patients to increased risk for BSI.

PMID- 19406333
TI  - Needlestick injuries: does left-handedness matter?

PMID- 19406334
TI  - Postexposure measles preparedness in resource-limited settings.

PMID- 19406336
TI  - Nephrogenic systemic fibrosis: pathogenesis, diagnosis, and therapy.
AB  - Nephrogenic systemic fibrosis (NSF) is a newly recognized disorder occurring
      exclusively in patients with renal failure. Exposure to gadolinium-based magnetic
      resonance (MR) contrast media has been associated with subsequent development of
      NSF. Nephrogenic systemic fibrosis is characterized by skin induration
      preferentially affecting the extremities. In addition, involvement of internal
      organs occurs, which leads ultimately to death. Skin biopsy is important for
      confirmation of the diagnosis. The main therapeutic goal is restoration of renal
      function. To reduce the risk of NSF, renal function must be determined before
      exposure to gadolinium-containing MR contrast agents. Gadolinium-based MR
      contrast media should be avoided in the presence of advanced renal failure with
      estimated glomerular filtration rate below 30 ml/min/1.73 m2, unless the
      diagnostic information is essential and not available with noncontrast magnetic
      resonance imaging techniques. The recommended dose of contrast agent should not
      be exceeded. In addition, a sufficient period of time for elimination of the
      contrast agent from the body should be allowed before readministration of the
      contrast agent.

PMID- 19406337
TI  - Clinical effectiveness of coronary stents in elderly persons: results from
      262,700 Medicare patients in the American College of Cardiology-National
      Cardiovascular Data Registry.
AB  - OBJECTIVES: The aim of this study was to compare outcomes in older individuals
      receiving drug-eluting stents (DES) and bare-metal stents (BMS). BACKGROUND:
      Comparative effectiveness of DES relative to BMS remains unclear. METHODS:
      Outcomes were evaluated in 262,700 patients from 650 National Cardiovascular Data
      Registry sites during 2004 to 2006 with procedural registry data linked to
      Medicare claims for follow-up. Outcomes including death, myocardial infarction
      (MI), revascularization, major bleeding, stroke, death or MI, death or MI or
      revascularization, and death or MI or stroke were compared with estimated
      cumulative incidence rates with inverse probability weighted estimators and Cox
      proportional hazards ratios. RESULTS: The DES were implanted in 217,675 patients
      and BMS were implanted in 45,025. At 30 months, DES patients had lower unadjusted
      rates of death (12.9% vs. 17.9%), MI (7.3 of 100 patients vs. 10.0 of 100
      patients), and revascularization (23.0 of 100 patients vs. 24.5 of 100 patients)
      with no difference in stroke or bleeding. After adjustment, DES patients had
      lower rates of death (13.5% vs. 16.5%, hazard ratio [HR]: 0.75, 95% confidence
      interval [CI]: 0.72 to 0.79, p < 0.001) and MI (7.5 of 100 patients vs. 8.9 of
      100 patients, HR: 0.77, 95% CI: 0.72 to 0.81, p < 0.001), with minimal difference
      in revascularization (23.5 of 100 patients vs. 23.4 of 100 patients; HR: 0.91,
      95% CI: 0.87 to 0.96), stroke (3.1 of 100 patients vs. 2.7 of 100 patients, HR:
      0.97, 95% CI: 0.88 to 1.07), or bleeding (3.4 of 100 patients vs. 3.6 of 100
      patients, HR: 0.91, 95% CI: 0.84 to 1.00). The DES survival benefit was observed
      in all subgroups analyzed and persisted throughout 30 months of follow-up.
      CONCLUSIONS: In this largest ever real-world study, patients receiving DES had
      significantly better clinical outcomes than their BMS counterparts, without an
      associated increase in bleeding or stroke, throughout 30 months of follow-up and
      across all pre-specified subgroups.

PMID- 19406339
TI  - Evaluating use of coronary computed tomography angiography in the emergency
      department.

PMID- 19406338
TI  - Coronary computed tomography angiography for early triage of patients with acute
      chest pain: the ROMICAT (Rule Out Myocardial Infarction using Computer Assisted
      Tomography) trial.
AB  - OBJECTIVES: This study was designed to determine the usefulness of coronary
      computed tomography angiography (CTA) in patients with acute chest pain.
      BACKGROUND: Triage of chest pain patients in the emergency department remains
      challenging. METHODS: We used an observational cohort study in chest pain
      patients with normal initial troponin and nonischemic electrocardiogram. A 64
      slice coronary CTA was performed before admission to detect coronary plaque and
      stenosis (>50% luminal narrowing). Results were not disclosed. End points were
      acute coronary syndrome (ACS) during index hospitalization and major adverse
      cardiac events during 6-month follow-up. RESULTS: Among 368 patients (mean age 53
      +/- 12 years, 61% men), 31 had ACS (8%). By coronary CTA, 50% of these patients
      were free of coronary artery disease (CAD), 31% had nonobstructive disease, and
      19% had inconclusive or positive computed tomography for significant stenosis.
      Sensitivity and negative predictive value for ACS were 100% (n = 183 of 368; 95%
      confidence interval [CI]: 98% to 100%) and 100% (95% CI: 89% to 100%),
      respectively, with the absence of CAD and 77% (95% CI: 59% to 90%) and 98% (n =
      300 of 368, 95% CI: 95% to 99%), respectively, with significant stenosis by
      coronary CTA. Specificity of presence of plaque and stenosis for ACS were 54%
      (95% CI: 49% to 60%) and 87% (95% CI: 83% to 90%), respectively. Only 1 ACS
      occurred in the absence of calcified plaque. Both the extent of coronary plaque
      and presence of stenosis predicted ACS independently and incrementally to
      Thrombolysis In Myocardial Infarction risk score (area under curve: 0.88, 0.82,
      vs. 0.63, respectively; all p < 0.0001). CONCLUSIONS: Fifty percent of patients
      with acute chest pain and low to intermediate likelihood of ACS were free of CAD
      by computed tomography and had no ACS. Given the large number of such patients,
      early coronary CTA may significantly improve patient management in the emergency
      department.

PMID- 19406340
TI  - A prospective, randomized, 6-month comparison of the coronary vasomotor response
      associated with a zotarolimus- versus a sirolimus-eluting stent: differential
      recovery of coronary endothelial dysfunction.
AB  - OBJECTIVES: We prospectively compared coronary endothelial dysfunction in
      patients with zotarolimus-eluting stent (ZES) versus sirolimus-eluting stent
      (SES) implantation at 6-month follow-up. BACKGROUND: A ZES has been associated
      with uniform and rapid healing of the endothelium. METHODS: Fifty patients were
      randomly treated with intravascular ultrasound-guided stenting with a single
      stent to the mid-segment of the left anterior descending artery (20 ZES, 20 SES,
      and 10 bare-metal stents), and endothelial function was estimated before and
      after intervention at 6-month follow-up by incremental acetylcholine (Ach) (10,
      20, 50, and 100 microg/min) and nitrate (200 microg/min) infusions into the left
      coronary ostium. The vascular response was quantitatively measured in the 5-mm
      segments proximal and distal to the stent. RESULTS: In the drug-eluting stent
      groups, more intense vasoconstriction to incremental doses of Ach was observed at
      6-month follow-up compared with the responses before stenting. Endothelial
      function associated with the ZES was more preserved at 6-month follow-up compared
      with the SES. Vasoconstriction to Ach was more prominent in the distal segments
      than the proximal segments in both the ZES and SES groups. Endothelium
      independent vasodilation to nitrate did not differ significantly among the study
      groups. CONCLUSIONS: Vasoconstriction in response to Ach in the peri-stent region
      was less pronounced in the ZES group than the SES group at 6-month follow-up,
      which suggests that endothelial function associated with ZES can be more
      preserved than the SES.

PMID- 19406341
TI  - Differences in restenosis rate with different drug-eluting stents in patients
      with and without diabetes mellitus: a report from the SCAAR (Swedish Angiography
      and Angioplasty Registry).
AB  - OBJECTIVES: Our aim was to evaluate restenosis rate of drug-eluting stents (DES)
      in patients with and without diabetes mellitus (DM) in a real-world setting.
      BACKGROUND: DES seem less effective in patients with DM. METHODS: The SCAAR
      (Swedish Coronary Angiography and Angioplasty Registry) includes all patients
      undergoing percutaneous coronary intervention in Sweden. From April 1, 2004, to
      April 20, 2008, all restenoses detected at a subsequent angiography and all DES
      types implanted at more than 500 occasions were assessed using Cox regression.
      RESULTS: Four DES types qualified for inclusion. In total, 35,478 DES were
      implanted at 22,962 procedures in 19,004 patients and 1,807 restenoses were
      reported over a mean 29 months follow-up. In the entire population, the
      restenosis rate per stent was 3.5% after 1 year and 4.9% after 2 years. The
      adjusted risk of restenosis was higher in patients with DM compared with that in
      patients without DM (relative risk [RR]: 1.23, 95% confidence interval [CI]: 1.10
      to 1.37). In patients with DM, restenosis was twice as frequent with the
      zotarolimus-eluting Endeavor stent (Medtronic, Minneapolis, Minnesota) compared
      with that in the other DES types. The Endeavor stent and the sirolimus-eluting
      Cypher stent (Cordis, Johnson & Johnson, Miami, Florida) had higher restenosis
      rates in patients with DM compared with those in patients without DM (RR: 1.77,
      95% CI: 1.29 to 2.43 and RR: 1.25, 95% CI: 1.04 to 1.51). Restenosis rate with
      the paclitaxel-eluting Taxus Express and Liberte (Boston Scientific, Natick,
      Massachusetts) stents was unrelated to DM. Mortality did not differ between
      different DES. CONCLUSIONS: Restenosis rate with DES was higher in patients with
      DM compared with that in patients without DM. There seem to be important
      differences between different brands of DES.

PMID- 19406342
TI  - Benefits from small molecule administration as compared with abciximab among
      patients with ST-segment elevation myocardial infarction treated with primary
      angioplasty: a meta-analysis.
AB  - OBJECTIVES: The aim of the study was to perform a meta-analysis of randomized
      trials (RTs) comparing abciximab versus small molecules (eptifibatide and
      tirofiban) in primary angioplasty (PPCI) for ST-segment elevation myocardial
      infarction (STEMI). BACKGROUND: Abciximab has been shown to provide significant
      benefits in PPCI for STEMI. However, small molecules represent an attractive
      strategy due to the reversibility of the inhibition of platelet aggregation and
      the lower costs. METHODS: We obtained results from RTs comparing abciximab versus
      small molecules in PPCI. The literature was scanned by searches of electronic
      databases (MEDLINE and CENTRAL) up to October 2008. The following key words were
      used: RT, myocardial infarction, reperfusion, primary angioplasty, glycoprotein
      IIb/IIIa inhibitors, abciximab, tirofiban, and eptifibatide. Concerning
      tirofiban, we only included trials or groups of patients with high-dose bolus and
      infusion. The primary end point was 30-day mortality. Secondary end points were
      30-day reinfarction, post-procedural Thrombolysis In Myocardial Infarction (TIMI)
      flow grade 3, and ST-segment resolution. RESULTS: A total of 6 RTs were included
      in the meta-analysis, involving 2,197 patients (1,082 randomized to abciximab and
      1,115 to small molecules [high-dose tirofiban in 5 trials and eptifibatide in 1
      trial]). Abciximab did not improve post-procedural TIMI flow grade 3 (89.8% vs.
      89.1%, p = 0.72) or ST-segment resolution (67.8% vs. 68.2%, p = 0.66). Abciximab
      did not reduce 30-day mortality (2.2% vs. 2.0%, p = 0.66) or reinfarction (1.2%
      vs. 1.2%, p = 0.88), nor was there any difference in major bleeding complications
      (1.3% vs. 1.9%, p = 0.27). CONCLUSIONS: This meta-analysis shows among STEMI
      patients undergoing PPCI similar results between abciximab and small molecules in
      terms of angiographic, electrocardiographic, and clinical outcome.

PMID- 19406343
TI  - The benefits of platelet glycoprotein IIb/IIIa receptor inhibition during primary
      percutaneous coronary intervention for ST-segment elevation myocardial
      infarction: drug-specific or class effect?

PMID- 19406344
TI  - Use of drug-eluting stents in acute myocardial infarction: a systematic review
      and meta-analysis.
AB  - OBJECTIVES: The primary aim of the analysis was to compare outcomes by stent type
      for death, myocardial infarction (MI), target vessel revascularization (TVR), and
      stent thrombosis in randomized trials of ST-segment elevation myocardial
      infarction (STEMI). A secondary analysis was performed among registry studies.
      BACKGROUND: It is not known whether there are differences in outcomes between
      drug-eluting stents (DES) and bare-metal stents (BMS) for STEMI. METHODS: We
      searched MEDLINE, EMBASE, the Cochrane Library, and Internet sources for articles
      comparing outcomes between DES and BMS among patients with STEMI between January
      2000 and October 2008. Randomized controlled trials and registries including
      patients 18 years of age and older receiving a DES or BMS were included. We
      extracted variables related to the study design, setting, participants, and
      clinical end points. RESULTS: Thirteen randomized trials were identified (N =
      7,352). Compared with BMS, DES significantly reduced TVR (relative risk [RR]:
      0.44; 95% confidence interval [CI]: 0.35 to 0.55), without increasing death (RR:
      0.89; 95% CI: 0.70 to 1.14), MI (RR: 0.82; 95% CI: 0.64 to 1.05), or stent
      thrombosis (RR: 0.97; 95% CI: 0.73 to 1.28). These observations were durable over
      2 years. Among 18 registries (N = 26,521), DES significantly reduced TVR (RR:
      0.54; 95% CI: 0.40 to 0.74) without an increase in MI (RR: 0.87, 95% CI: 0.62 to
      1.23). Death was significantly lower in the DES group within 1 year of the index
      percutaneous coronary intervention, but there were no differences within 2 years
      (p = 0.45). CONCLUSIONS: The use of DES appears safe and efficacious in
      randomized trials and registries of patients with STEMI. The DES significantly
      reduce TVR compared with BMS, without an increase in death, MI, or stent
      thrombosis within 2 years of the index procedure.

PMID- 19406345
TI  - Atrial fibrillation and heart failure in cardiology practice: reciprocal impact
      and combined management from the perspective of atrial fibrillation: results of
      the Euro Heart Survey on atrial fibrillation.
AB  - OBJECTIVES: Our aim was to identify shortcomings in the management of patients
      with both atrial fibrillation (AF) and heart failure (HF). BACKGROUND: AF and HF
      often coincide in cardiology practice, and they are known to worsen each other's
      prognosis, but little is known about the quality of care of this combination.
      METHODS: In the observational Euro Heart Survey on AF, 5,333 AF patients were
      enrolled in 182 centers across 35 European Society of Cardiology member countries
      in 2003 and 2004. A follow-up survey was performed after 1 year. RESULTS: At
      baseline, 1,816 patients (34%) had HF. Recommended therapy for HF with left
      ventricular systolic dysfunction (LVSD) with a beta-blocker and either an
      angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker
      was prescribed in 40% of HF patients, while 29% received the recommended drug
      therapy for both LVSD-HF and AF, consisting of the combination of a beta-blocker,
      either ACEI or angiotensin II receptor blocker, and oral anticoagulation. Rate
      control was insufficient with 40% of all HF patients with permanent AF having a
      heart rate < or =80 beats/min. In the total cohort, HF patients had a higher risk
      for mortality (9.5% vs. 3.3%; p < 0.001), (progression of) HF (24.8% vs. 5.0%; p
      < 0.001), and AF progression (35% vs. 19%; p < 0.001) during 1-year follow-up. Of
      all recommended drugs for AF and LVSD-HF, only ACEI prescription was associated
      with improved survival during 1-year follow-up (odds ratio: 0.51 [95% confidence
      interval: 0.31 to 0.85]; p = 0.011). CONCLUSIONS: The prescription rate of
      guideline-recommended drug therapy for AF and LVSD-HF is low. Randomized
      controlled trials targeting this highly prevalent subgroup with AF and HF are
      warranted.

PMID- 19406346
TI  - Characterization of peri-infarct zone heterogeneity by contrast-enhanced
      multidetector computed tomography: a comparison with magnetic resonance imaging.
AB  - OBJECTIVES: This study examined whether multidetector computed tomography (MDCT)
      improves the ability to define peri-infarct zone (PIZ) heterogeneity relative to
      magnetic resonance imaging (MRI). BACKGROUND: The PIZ as characterized by delayed
      contrast-enhancement (DE)-MRI identifies patients susceptible to ventricular
      arrhythmias and predicts outcome after myocardial infarction (MI). METHODS:
      Fifteen mini-pigs underwent coronary artery occlusion followed by reperfusion.
      Both MDCT and MRI were performed on the same day approximately 6 months after MI
      induction, followed by animal euthanization and ex vivo MRI (n = 5). Signal
      density threshold algorithms were applied to MRI and MDCT datasets reconstructed
      at various slice thicknesses (1 to 8 mm) to define the PIZ and to quantify
      partial volume effects. RESULTS: The DE-MDCT reconstructed at 8-mm slice
      thickness showed excellent correlation of infarct size with post-mortem pathology
      (r2 = 0.97; p < 0.0001) and MRI (r2 = 0.92; p < 0.0001). The DE-MDCT and -MRI
      were able to detect a PIZ in all animals, which correlates to a mixture of viable
      and nonviable myocytes at the PIZ by histology. The ex vivo DE-MRI PIZ volume
      decreased with slice thickness from 0.9 +/- 0.2 ml at 8 mm to 0.2 +/- 0.1 ml at 1
      mm (p = 0.01). The PIZ volume/mass by DE-MDCT increased with decreasing slice
      thickness because of declining partial volume averaging in the PIZ, but was
      susceptible to increased image noise. CONCLUSIONS: A DE-MDCT provides a more
      detailed assessment of the PIZ in chronic MI and is less susceptible to partial
      volume effects than MRI. This increased resolution best reflects the extent of
      tissue mixture by histopathology and has the potential to further enhance the
      ability to define the substrate of malignant arrhythmia in ischemic heart disease
      noninvasively.

PMID- 19406348
TI  - Imaging of de novo atherosclerotic arterial remodeling: clinical sense or
      research sensibility?

PMID- 19406347
TI  - Positive remodeling of the coronary arteries detected by magnetic resonance
      imaging in an asymptomatic population: MESA (Multi-Ethnic Study of
      Atherosclerosis).
AB  - OBJECTIVES: The purpose of this study was to assess coronary arterial remodeling
      as a marker of subclinical atherosclerosis using coronary wall magnetic resonance
      imaging (MRI) in an asymptomatic population-based cohort. BACKGROUND: In early
      atherosclerosis, compensatory enlargement of both the outer wall of the vessel as
      well as the lumen, termed compensatory enlargement or positive remodeling, occurs
      before luminal narrowing. METHODS: One hundred seventy-nine participants in the
      MESA (Multi-Ethnic Study of Atherosclerosis) trial were evaluated using black
      blood coronary wall MRI. Coronary cross-sectional area (vessel size), lumen area,
      and mean wall thickness of the proximal coronary arteries were measured. RESULTS:
      Men had a greater vessel size, lumen area, and mean wall thickness than women
      (38.3 +/- 11.3 mm2 vs. 32.6 +/- 9.4 mm2, 6.7 +/- 3.2 mm2 vs. 5.3 +/- 2.4 mm2, and
      2.0 +/- 0.3 mm vs. 1.9 +/- 0.3 mm, respectively, p < 0.05). No significant
      coronary artery narrowing was present by magnetic resonance angiography. Overall,
      coronary vessel size increased 25.9 mm2 per millimeter increase in coronary wall
      thickness, whereas lumen area increased only slightly at 3.1 mm2 for every
      millimeter increase in wall thickness (difference in slopes, p < 0.0001).
      Adjusting for age and sex, participants with an Agatston score >0 were more
      likely to have wall thickness >2.0 mm (odds ratio: 2.0, 95% confidence interval:
      1.01 to 3.84). CONCLUSIONS: Coronary wall MRI detected positive arterial
      remodeling in asymptomatic men and women with subclinical atherosclerosis.

PMID- 19406349
TI  - Impact of a worksite intervention program on cardiovascular risk factors: a
      demonstration project in an Indian industrial population.

PMID- 19406351
TI  - President's page: what is a cardiologist?

PMID- 19406350
TI  - Cardioembolic source of ST-segment elevation myocardial infarction.

PMID- 19406352
TI  - Clinical applications of MR diffusion and perfusion imaging: Preface.

PMID- 19406354
TI  - Diffusion MR tractography as a tool for surgical planning.
AB  - Diffusion MR tractography has rapidly become an important clinical tool that can
      delineate functionally important white matter tracts for surgical planning. One
      of the goals of brain surgery is to avoid damage to eloquent cortex and
      subcortical white matter. Diffusion tractography remains the only noninvasive
      method capable of segmenting the subcortical course of a white matter tract. This
      article reviews the technical and clinical issues surrounding presurgical
      diffusion tractography, including traditional diffusion tensor imaging methods
      and more advanced high angular resolution diffusion imaging approaches, such as q
      ball imaging. An overview of the presurgical diffusion tensor imaging and q-ball
      tractography protocols used at our institution is also provided.

PMID- 19406355
TI  - Update on diffusion tensor imaging in Alzheimer's disease.
AB  - With estimates of more than 5 million people with Alzheimer's disease (AD) now
      living in the United States and an increasing prevalence of the disease among the
      aging population, there is an urgent need for the development of reliable
      biomarkers for early diagnosis and evaluation of potential therapeutic
      interventions. Structural MR imaging, the focus of the most intense research in
      this area to date, has identified characteristic patterns of macroscopic atrophy
      within larger groups of patients who have clinically probable AD, particularly
      within the medial temporal lobes. These changes are thought to reflect underlying
      neuronal cell death, and as a result are consistently demonstrated only in the
      late stages of the disease. Paralleling the development of new molecular markers
      for AD pathology in nuclear medicine are a number of encouraging results in the
      application of functional, perfusion, and diffusion imaging which point to a
      growing role for MR imaging in the evaluation of AD. This article surveys current
      research on the use of diffusion MR imaging for the evaluation of patients who
      have mild cognitive impairment and AD, and summarizes the important unifying
      results that are beginning to emerge on the potential role for diffusion imaging
      in practice.

PMID- 19406356
TI  - Diffusion-weighted imaging, diffusion-tensor imaging, and fiber tractography of
      the spinal cord.
AB  - In the brain, diffusion-weighted imaging (DWI) is an established and reliable
      method for the characterization of neurologic lesions. Although the diagnostic
      value of DWI in the early detection of ischemia has not diminished with time,
      many new clinical applications of DWI have also emerged. Diffusion-tensor imaging
      and fiber tractography have more recently been developed and optimized, allowing
      quantification of the magnitude and direction of diffusion along three principal
      eigenvectors. Diffusion-tensor imaging and fiber tractography are proving to be
      useful in clinical neuroradiology practice, with application to several
      categories of disease, and to be a powerful research tool. This article describes
      some of the applications of DWI and diffusion-tensor imaging in the evaluation of
      the diseases of the spinal cord.

PMID- 19406353
TI  - New methods in diffusion-weighted and diffusion tensor imaging.
AB  - Considerable strides have been made by countless individual researchers in
      diffusion-weighted imaging (DWI) to push DWI from an experimental tool, limited
      to a few institutions with specialized instrumentation, to a powerful tool used
      routinely for diagnostic imaging. The field of DWI constantly evolves, and
      progress has been made on several fronts. These developments are primarily
      composed of improved robustness against patient and physiologic motion, increased
      spatial resolution, new biophysical and tissue models, and new clinical
      applications for DWI. This article aims to provide a succinct overview of some of
      these new developments and a description of some of the major challenges
      associated with DWI.

PMID- 19406357
TI  - Diffusion-weighted MR imaging for whole body metastatic disease and
      lymphadenopathy.
AB  - Diffusion-weighted (DW) imaging provides a new contrast mechanism for evaluation
      of tumors of the chest, abdominal, and pelvis. By imaging microscopic motion of
      water molecules, DW imaging yields new qualitative and quantitative information
      about tumors that can be used to improve tumor detection, characterize some
      tumors, and monitor and predict response to treatment. DW imaging techniques
      provide a host of new tools for the body imager including: magnitude DW images;
      ADC maps with quantitative analysis; and volumetric display of data including
      whole body diffusion with background suppression. Experience with these DW
      techniques for body applications is still accumulating. However, DW imaging has
      already become an integral part of body MR imaging protocols at many centers.

PMID- 19406358
TI  - Diffusion-weighted MR imaging in musculoskeletal radiology: applications in
      trauma, tumors, and inflammation.
AB  - Diffusion-weighted imaging is a noninvasive magnetic resonance technique that is
      capable of measuring icroscopic movement of water molecules (ie, random or
      Brownian motion) within biologic tissues. Diffusion weighting is achieved with a
      pulsed-field gradient that leaves "static" spins unaffected but causes dephasing
      of spin ensembles that experience different motion histories according to their
      diffusion paths, with respect to the direction of the gradient. This article
      focuses on the interesting opportunities of the use of diffusion weighted imaging
      in the diagnosis of musculoskeletal diseases, including trauma, tumor, and
      inflammation.

PMID- 19406359
TI  - Fundamentals of quantitative dynamic contrast-enhanced MR imaging.
AB  - Quantitative analysis of dynamic contrast-enhanced MR imaging (DCE-MR imaging)
      has the power to provide information regarding physiologic characteristics of the
      microvasculature and is, therefore, of great potential value to the practice of
      oncology. In particular, these techniques could have a significant impact on the
      development of novel anticancer therapies as a promising biomarker of drug
      activity. Standardization of DCE-MR imaging acquisition and analysis to provide
      more reproducible measures of tumor vessel physiology is of crucial importance to
      realize this potential. The purpose of this article is to review the
      pathophysiologic basis and technical aspects of DCE-MR imaging techniques.

PMID- 19406360
TI  - Diffusion and perfusion MR imaging of acute ischemic stroke.
AB  - Diffusion and perfusion MR imaging have proven to be highly useful in the
      clinical description and understanding of acute and hyperacute ischemic stroke.
      In this article, the authors give a brief overview of the basic concepts of
      diffusion and perfusion imaging and describe some of the current developments,
      applications, challenges, and limitations of these techniques as applied to
      cerebral ischemia.

PMID- 19406362
TI  - Dynamic contrast-enhanced MR imaging of the liver: current status and future
      directions.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MR imaging) is emerging
      as a tool that can quantify changes in liver perfusion that occur in both diffuse
      and focal liver diseases. Recent data show promise for DCE-MR imaging of the
      liver in diagnosing fibrosis and cirrhosis before morphologic changes can be
      detected. It may also be valuable in the assessment of hepatocellular carcinoma
      and liver metastases. Acquisition parameters, postprocessing methods,
      applications, and recent results of DCE-MR imaging of the liver are also
      described. Finally, it reviews the limitations and future directions of DCE-MR
      imaging for liver applications.

PMID- 19406363
TI  - Dynamic contrast-enhanced breast MR imaging.
AB  - This article discusses the basic principles of dynamic contrast-enhanced MR
      imaging (DCE-MR imaging) of the breast, including technical parameters, image
      acquisition, and image interpretation. Clinical DCE-MR imaging of the breast has
      undergone considerable growth from a once investigational technique to an
      important clinical tool in widespread use. Progress in MR technology and
      refinement of MR imaging parameters now allow for concurrent acquisition of high
      spatial-resolution and adequate-temporal-resolution images, which are necessary
      for accurate assessment of breast lesion morphology and qualitative kinetic
      analysis. More advanced DCE-MR imaging techniques involving higher-temporal
      resolution images and rigorous quantitative analysis of the time signal
      enhancement curves are currently an area of research.

PMID- 19406364
TI  - Dynamic contrast-enhanced MR imaging in the evaluation of patients with prostate
      cancer.
AB  - Prostate cancer is a common tumor among men, with increasing diagnosis at an
      earlier stage and a lower volume of disease because of screening with prostate
      specific antigen (PSA). The need for imaging of the prostate stems from a desire
      to optimize treatment strategy on a patient and tumor-specific level. The major
      goals of prostate imaging are (1) staging of known cancer, (2) determination of
      tumor aggressiveness, (3) diagnosis of cancer in patients who have elevated PSA
      but a negative biopsy, (4) treatment planning, and (5) the evaluation of therapy
      response. This article concentrates on the role of dynamic contrast-enhanced MR
      imaging in the evaluation of patients who have prostate cancer and how it might
      be used to help achieve the above goals. Various dynamic contrast enhancement
      approaches (quantitative/semiquantitative/qualitative, high temporal versus high
      spatial resolution) are summarized with reference to the relevant strengths and
      compromises of each approach.

PMID- 19406361
TI  - Arterial spin-labeled MR perfusion imaging: clinical applications.
AB  - Arterial spin labeling (ASL) imaging soon will be available as a routine clinical
      perfusion imaging sequence for a significant number of MR imaging scanners. The
      ASL perfusion technique offers information similar to that provided by
      conventional dynamic susceptibility sequences, but it does not require the use of
      an intravenous contrast agent, and the data can be quantified. The appearance of
      pathology is affected significantly by the ASL techniques used. Familiarity with
      the available sequence parameter options and the common appearances of pathology
      facilitates perfusion interpretation.

PMID- 19406365
TI  - Pain experience: perception and therapy.

PMID- 19406366
TI  - Fibromyalgia: diagnosis and treatment options.
AB  - BACKGROUND: Fibromyalgia is a widespread, chronic pain disorder that includes a
      complex constellation of somatic and emotional symptoms. Controlled clinical
      trials for both medication and nonmedication therapies have led to sound,
      evidence-based recommendations for the care of patients with fibromyalgia.
      OBJECTIVE: This review article was designed to provide updated information from
      database literature searches on fibromyalgia epidemiology, including gender
      differences, psychological comorbidity, and treatment with medication and
      nonmedication therapies. METHODS: A literature review was performed by
      identifying fibromyalgia articles published in English from January 2000 to
      October 2008 using the PubMed and EMBASE databases. Search terms included
      fibromyalgia, exercise, gender, nonpharmacologic, placebo-controlled, randomized,
      and treatment. RESULTS: New epidemiologic data support important differences in
      fibromyalgia symptom severity between the sexes and the important role of
      comorbid psychological distress. Physicians diagnose fibromyalgia in women at an
      approximately 3- to 6-fold rate compared with men. Well-conducted clinical trials
      and recently published treatment guidelines reinforce effective treatment with
      medication and nonpharmacologic therapy. The strongest evidence suggests
      effective treatment of fibromyalgia with duloxetine and milnacipran. Studies also
      report efficacy with gabapentin, pramipexole, pregabalin, tramadol, and IV
      tropisetron. Nonpharmacologic treatments should include fitness and strengthening
      exercise, as well as warm-water therapy and psychological pain management
      techniques. CONCLUSIONS: Fibromyalgia is a common, disabling, chronic pain
      condition that predominantly affects women. Symptoms can be effectively treated
      using both drug and nondrug therapies. In general, treatment benefits in
      fibromyalgia appear largely independent of patient sex.

PMID- 19406368
TI  - Ovarian hormones and pain response: a review of clinical and basic science
      studies.
AB  - BACKGROUND: Most clinical pain disorders are more common in women than in men,
      particularly during the peak reproductive years. This suggests that fluctuations
      in the ovarian hormones encountered during the female menstrual cycle may
      increase pain response. OBJECTIVES: This article examined whether pain severity
      and experimental pain thresholds vary during the phases of the menstrual cycle in
      women with and without clinical pain disorders. It also reviewed the effect of
      ovarian hormones on behavioral responses to painful stimuli (pain reactivity) in
      animal models and the potential mechanisms through which ovarian hormones
      modulate pain reactivity. METHODS: A narrative review was performed to ascertain
      the relationship between ovarian hormones and pain response. Relevant English
      language publications describing pain reactivity in premenopausal women and
      female rodents were identified through searches of MEDLINE and PubMed from
      January 1, 1967, through May 1, 2008, as well as through the reference lists of
      identified articles. RESULTS: In the clinical studies reviewed, most pain
      disorders were reported to worsen during the late luteal and early follicular
      phases of the menstrual cycle. Pain thresholds and tolerance times also varied
      during different phases of the menstrual cycle in healthy premenopausal women in
      the majority of studies. Basic science studies suggested that ovarian hormones
      have distinct effects-on inflammation, affective states, stress responses,
      modulatory pain systems, and afferent sensory systems-that increase or decrease
      pain reactivity. CONCLUSIONS: Fluctuations of ovarian hormones in the course of
      the menstrual cycle appear to be associated with a mild to moderate effect on
      pain response. Greater knowledge of the mechanisms by which ovarian hormones
      modulate pain would broaden our understanding of why pain disorders are more
      frequent, severe, and disabling in women than in men.

PMID- 19406367
TI  - Do fluctuations in ovarian hormones affect gastrointestinal symptoms in women
      with irritable bowel syndrome?
AB  - BACKGROUND: An increase in gastrointestinal (GI) symptoms, including bowel
      discomfort, abdominal pain/discomfort, bloating, and alterations in bowel
      patterns, has been reported during premenses and menses menstrual cycle phases
      and the perimenopause period in women with and without irritable bowel syndrome
      (IBS). OBJECTIVE: This article reviews the literature related to one possible
      physiological mechanism-declining or low ovarian hormone levels--that may
      underlie the occurrence or exacerbations of abdominal pain/discomfort at times of
      low ovarian hormones (menses, menopause) in women with or without IBS. METHODS:
      To identify English-only review and data-based articles, PubMed was searched
      between January 1980 and September 2008 using the following terms: irritable
      bowel syndrome, functional gastrointestinal disorders, gastrointestinal motility,
      immune, pain, hyperalgesia, menstrual cycle, menopause, pregnancy, estrogen,
      estradiol (E(2)), and progesterone. Studies in animals and in humans were
      included; drug trials were excluded. RESULTS: From our review of the literature,
      18 papers were identified that were related either to the mechanisms accounting
      for menstrual cycle fluctuations (n = 12) or to the impact of menopausal status
      on symptoms of IBS (n = 6). One study reported that visceral pain sensitivity was
      significantly higher during menses than at other menstrual cycle phases in women
      with IBS (P < 0.05). Other menstrual cycle phase-linked symptoms, dysmenorrheal
      symptoms (cramping pain) in particular, were more intense in women with IBS.
      Animal studies have shed some light on the relationship of ovarian hormones to GI
      sensorimotor function. CONCLUSION: The increase in GI symptoms around the time of
      menses and early menopause occurs at times of declining or low ovarian hormones,
      suggesting that estrogen and progesterone withdrawal may contribute either
      directly or indirectly. This review highlights the need for confirmatory
      preclinical and clinical studies to unravel the role of ovarian hormones in women
      with IBS.

PMID- 19406370
TI  - Sexual differentiation of rat reproductive versus opioid antinociceptive systems.
AB  - BACKGROUND: It has been suggested that sexual differentiation of opioid analgesic
      sensitivity may parallel sexual differentiation in reproductive systems.
      OBJECTIVE: The present study compared organizational and activational roles of
      testosterone in sexual differentiation in reproductive versus opioid
      antinociceptive systems in the rat, to assess whether both systems were similarly
      testosterone dependent. METHODS: Male rat pups (Sprague-Dawley and Fisher 344
      [F344]) were either handled or castrated on postnatal day (PND) 1, and female
      pups were injected with testosterone propionate (100 or 1000 microg) on PND 2. In
      adulthood, all rats were gonadectomized (or simply anesthetized) and implanted
      with either testosterone filled or blank capsules (one 10-mm capsule/100 g of
      body weight). RESULTS: Two hundred one Sprague-Dawley rats and 178 F344 rats were
      used. In gonadally intact adults of both rat strains, the antinociceptive potency
      of subcutaneously injected morphine was significantly greater in males than in
      females (P < or = 0.05). These sex differences were eliminated by neonatal
      castration in males or by neonatal androgenization in females. However, adult
      testosterone treatment reversed the effects of neonatal castration in males.
      Masculinization and defeminization of sexual behavior, ovary weight, and body
      weight generally met conventional expectations. Compared with male controls,
      neonatally castrated males gained less body weight, and displayed more lordosis
      behavior and compromised male sexual behaviors. Compared with female controls,
      neonatally androgenized females gained more body weight, developed smaller
      ovaries, and presented less lordosis behavior and more male sexual behaviors.
      Overall, neonatal testosterone manipulations sufficient to masculinize or
      defeminize rats in terms of reproductive behavior and physiology also
      masculinized or defeminized morphine antinociceptive sensitivity. The effects of
      neonatal castration were reversed by adult testosterone treatment, indicating
      that sexual differentiation of opioid antinociceptive systems begins before PND
      1. CONCLUSIONS: Sensitivity to opioid antinociception begins to diverge between
      males and females early in life. The relationship between gonadal hormone
      mediated sexual differentiation of the reproductive and the opioid
      antinociceptive systems suggests that the 2 systems may be functionally linked.
      This finding has implications for the treatment of pain and analgesia in women
      and men.

PMID- 19406369
TI  - Sex differences in the association between cortisol concentrations and laboratory
      pain responses in healthy children.
AB  - BACKGROUND: Research in adult populations has highlighted sex differences in
      cortisol concentrations and laboratory pain responses, with men exhibiting higher
      cortisol concentrations and reduced pain responses compared with women. Yet, less
      is known about the relationship of cortisol concentrations to pain in children.
      OBJECTIVE: This study examined associations between sex, cortisol, and pain
      responses to laboratory pain tasks in children. METHODS: Salivary cortisol
      samples from subjects aged 8 to 18 years were obtained at baseline after entering
      the laboratory (SCb), after the completion of all pain tasks (SC1), and at the
      end of the session (SC2), 20 minutes later. Blood cortisol samples were also
      taken after completion of the pain tasks (BC1) and at the end of the session
      (BC2), 20 minutes later. Subjects completed 3 counterbalanced laboratory pain
      tasks: pressure, heat, and cold pressor tasks. Pain measures included pain
      tolerance, and self-reported pain intensity and unpleasantness for all 3 tasks.
      RESULTS: The study included 235 healthy children and adolescents (119 boys, 116
      girls; mean age, 12.7 years; range, 8-18 years; 109 [46.4%] were in early
      puberty; 94 [40.0%] white). Salivary and blood cortisol levels were highly
      correlated with each other. Salivary cortisol levels for the total sample and for
      boys and girls declined significantly from SCb to SC1 (P < 0.01), although there
      were no significant changes from SC1 to SC2. No significant sex differences in
      salivary or blood cortisol levels were evident at any assessment point. Separate
      examination of the cortisol-laboratory pain response relationships by sex
      (controlling for age and time of day) suggested different sex-specific patterns.
      Higher cortisol levels were associated with lower pain reactivity (ie, increased
      pressure tolerance) among boys compared with girls at SC1, SC2, and BC1 (SC1: r =
      0.338, P = 0.003; SC2: r = 0.271, P = 0.020; and BC1: r = 0.261, P = 0.026).
      However, higher cortisol levels were related to higher pain response (ie,
      increased cold intensity [BC2: r = 0.229, P = 0.048] and unpleasantness [BC1: r =
      0.237, P = 0.041]) in girls compared with boys. CONCLUSIONS: These findings
      suggest important sex differences in cortisol-pain relationships in children and
      adolescents. Cortisol levels were positively associated with increased pain
      tolerance in boys and increased pain sensitivity in girls.

PMID- 19406371
TI  - Sex differences in the development of localized and spread mechanical
      hypersensitivity in rats after injury to the infraorbital or sciatic nerves to
      create a model for neuropathic pain.
AB  - BACKGROUND: Neuropathic pain after injury to the nervous system is a difficult
      clinical problem. Sex differences in the development of neuropathic pain have not
      been well established experimentally or clinically. OBJECTIVE: Rats were used to
      examine sex differences in localized and spread mechanical hypersensitivity after
      partial injury to their infraorbital or sciatic nerves in a model of neuropathic
      pain. METHODS: In adult female and male rats, partial nerve injury to the
      infraorbital and sciatic nerves was produced using a photochemical method.
      Mechanical hypersensitivity (allodynia) was examined and compared in the
      innervation territories of the nerves on the face or hind paw. The spread of
      hypersensitivity beyond the innervation territories of the injured nerves was
      also studied. The female and male rats were randomized to active and sham groups.
      The rats in the sham group had their sciatic or infraorbital nerve exposed, but
      not injured. RESULTS: A total of 67 rats (36 females, 31 males) were used. There
      was a marked sex difference in the response to infraorbital nerve injury: female
      rats developed more profound and long-lasting facial hypersensitivity than did
      male rats (P<0.001). Hypersensitivity of the hind paw after sciatic nerve injury
      did not, however, significantly differ between female and male rats. Spread
      mechanical hypersensitivity was noted in body areas outside the innervation
      territory of the injured nerve. This hypersensitivity was more profound after
      infraorbital than sciatic nerve injury and also displayed a significant sex
      difference (female>male, P < 0.001). Sham-group rats did not exhibit localized or
      spread mechanical hypersensitivity. CONCLUSION: Sex differences in the
      development of neuropathic painlike behaviors in rats were dependent on site of
      injury and site of testing, with female rats being more susceptible to the
      development of spread mechanical hypersensitivity, particularly after facial
      nerve injury, compared with male rats.

PMID- 19406373
TI  - Midwife-centered versus woman-centered care: a developmental phase?

PMID- 19406374
TI  - Mental body distance comparison: a tool for assessing clinical disturbances in
      visual body image.
AB  - Despite numerous body size estimation studies, it cannot be concluded that the
      disturbance of body image in anorexia nervosa (AN) is specifically one of the
      visual body images. We adopted a visual imagery method, the Distance Comparison
      task, to enable across-population testing of differences in visual body image
      with respect to shape. Participants were asked to mentally scan across two body
      widths (e.g. hips and shoulders) and to decide as quickly as possible which one
      was longer or shorter. If the mental representation accessed to make such
      comparisons is visual, an inverse relation would be expected between RT and
      distance difference on the body to be judged (i.e. actual difference in size
      between the two body widths), with accuracy increasing with increasing distance
      difference. Females with high body shape concern (scoring high on the Body Shape
      Questionnaire: BSQ, n=23) were compared to females with low body shape concern
      (scoring low on the BSQ, n=19). RT and distance differences on the body
      demonstrated standard distance differences effects: RT increased and accuracy
      decreased with decreasing distance differences on the body. Groups differed with
      respect to accuracy, in that females high on body shape concern were
      significantly less accurate than females low on body shape concern when making
      evaluations involving small (9cm) differences, which implies a less appropriate
      visual image of the own body in the former group. With respect to the relation
      between RT and body distance difference, on the other hand, there were no
      differences between groups. We concluded that evaluations of own body size employ
      visual imagery and that the distance comparison task holds promise for the
      assessment of visual disturbances in body image in clinical populations.

PMID- 19406372
TI  - Nociceptive and anxiety-like behavior in reproductively competent and
      reproductively senescent middle-aged rats.
AB  - BACKGROUND: Changes in levels of estradiol and progesterone that occur with the
      transition to reproductive senescence may influence nociception or affect.
      OBJECTIVE: To ascertain whether nociceptive and affective processes change with
      reproductive senescence, this study examined pain and anxiety-like behaviors in
      middle-aged female rats that were reproductively competent, transitioning to
      reproductive senescence, or reproductively senescent. METHODS: Middle-aged (12-14
      months old) female rats (N = 46) were tested in the following tasks to assess
      pain and anxiety-like behavior: tail flick, elevated plus maze, elevated zero
      maze, mirror maze, Vogel punished drinking, and defensive burying. For the tail
      flick task, the latency for rats to move their tail from a heat source, as an
      indication of pain sensitivity, was determined. In the elevated plus and elevated
      zero mazes, the time spent on the open arms or quadrants, respectively, were
      determined as measures of reduced anxiety behavior. In the mirror maze, the time
      spent in the mirrored portion of the chamber was used as an indicator of anxiety
      like responding. In the Vogel task, the number of punished licks made was
      determined as a measure of reduced anxiety-like behavior. In the defensive
      burying task, the duration spent by rats burying an electrified prod
      postfootshock was utilized as an index of anxietylike responding. All rats were
      experimentally naive, retired breeders from our colony and had not had a litter
      or been lactating for 1 to 4 weeks before behavioral testing. RESULTS: Although
      tail-flick latencies were not significantly different among rats that were
      reproductively competent or senescent, reproductively competent rats had less
      anxiety-like behavior in the elevated plus maze (more time spent on the open
      arms: F(2,43) = 5.93; P < 0.01), elevated zero maze (more time spent on the open
      quadrants: F(2,43) = 4.62; P = 0.01), and Vogel punished drinking task (more
      punished licks made: F(2,43) = 3.76; P = 0.03). There were no statistically
      significant differences in the mirror maze and defensive burying task.
      CONCLUSION: In this study of adult female rats, nociceptive behavior did not vary
      significantly with reproductive senescence, but anxiety-like behavior of rats
      did.

PMID- 19406375
TI  - Two eyes: square root 2 better than one?
AB  - Classical data on the detection of simple patterns show that two eyes are more
      sensitive than one eye. The degree of binocular summation is important for
      inferences about the underlying combination mechanism. In a signal detection
      theory framework, sensitivity is limited by internal noise. If noise is added
      centrally after binocular combination, binocular sensitivity is expected to be
      twice as good as monocular. If the noise is added peripherally at each eye prior
      to combination, binocular sensitivity will be sqrt[2] higher than monocular. In a
      large sample of observers (51), we measured contrast sensitivity for detection of
      gratings at several spatial frequencies using left, right, or both eyes.
      Estimates of binocular summation using both binocular summation ratios and
      Minkowski coefficients show a summation ratio with means in the range of 1.5-1.6.
      The 95% confidence interval overlaps with the value of sqrt[2] predicted by the
      peripheral noise model and does not overlap with the value of 2 predicted by the
      central noise model.

PMID- 19406376
TI  - Screening for diabetic retinopathy: 1 and 3 nonmydriatic 45-degree digital fundus
      photographs vs 7 standard early treatment diabetic retinopathy study fields.
AB  - PURPOSE: To evaluate if simple- or multiple-field digital color nonmydriatic (NM)
      retinal images can replace 7 standard stereoscopic fundus photographs in the
      screening of diabetic retinopathy (DR). DESIGN: Prospective, masked, comparative
      case series. METHODS: One hundred and eight eyes of 55 diabetics were studied to
      determine single lesions and to grade clinical levels of DR and diabetic macular
      edema (DME) using both 1 and 3 NM digital color retinal images compared with the
      Early Treatment Diabetic Retinopathy Study (ETDRS) 7 standard 35-mm stereoscopic
      color fundus photographs (7F-ETDRS). All eyes underwent NM 45-degree field images
      of 1 central field (1F-NM), NM 45-degree field images of 3 fields (3F-NM), and,
      after pupil dilatation, 30-degree 7F-ETDRS photography. Images were analyzed by 2
      independent, masked retinal specialists (S.V. and E.B.), lesion-by-lesion
      according to the ETDRS protocol and for clinical severity level of DR and DME
      according to the international classification of DR. RESULTS: Using 7F-ETDRS as
      the gold standard, agreement was substantial for grading clinical levels of DR
      and DME (kappa = 0.69 and kappa = 0.75) vs 3F-NM; moderate for DR level (kappa =
      0.56) and substantial for DME (kappa = 0.66) vs 1F-NM; almost perfect for
      detecting presence or absence of DR (kappa = 0.88) vs both 1F-NM and 3F-NM; and
      almost perfect for presence or absence of DME (kappa = 0.97) vs 3F-NM and
      substantial (kappa = 0.75) vs 1F-NM. Sensitivity and specificity for detecting
      referable levels of DR were 82% and 92%, respectively, for 3F-NM and 71% and 96%,
      respectively, for 1F-NM. CONCLUSIONS: Three color 45-degree NM fundus fields may
      be an effective tool in a screening setting to determine critical levels of DR
      and DME for prompt specialist referral. One central 45-degree image is sufficient
      to determine absence or presence of DR and DME, but not for grading it.

PMID- 19406378
TI  - Prevalence and outcomes of cataract surgery in Brazil: the Sao Paulo eye study.
AB  - PURPOSE: To investigate the prevalence and visual acuity (VA) outcomes of
      cataract surgery in a low- to middle-income population in Sao Paulo, Brazil.
      DESIGN: Population-based, cross-sectional study. METHODS: Cluster sampling was
      used in randomly selecting those > or =50 years old for VA measurement,
      refraction, and ocular examination. Participants were queried as to the year and
      type of facility for previous cataract surgery. Surgical procedure and evidence
      of surgical complications were noted. Main outcome measures were presenting and
      best-corrected vision, and the principal cause for eyes presenting with VA < or
      =20/40. RESULTS: A total of 4,224 eligible persons were enumerated and 3,678
      (87.1%) were examined. The prevalence of cataract surgery was 6.28% (95%
      confidence interval [CI], 5.29% to 7.27%). Surgical coverage for presenting VA
      <20/63 in both eyes because of cataract was 61.4%. Unoperated cataract
      impairment/blindness was associated with older age and lack of schooling. Among
      the 352 cataract-operated eyes, 41.2% presented with VA >20/40, 28.1% with VA
      20/40 to 20/63, 14.2% with VA <20/63 to 20/200, and 16.5% with VA <20/200. With
      best correction, the percentages were 61.9%, 17.6%, 8.2%, and 12.2%. Intraocular
      lenses were found in 90.6% of cataract-operated eyes; half appeared to have been
      operated by phacoemulsification. Refractive error and retinal disorders were the
      main cause of vision impairment/blindness in operated eyes. CONCLUSIONS: Cataract
      surgery has increased in Sao Paulo, but many remain visually impaired/blind
      because of cataract. Refractive error and other causes of impairment are common
      in cataract-operated eyes. Emphasis on the quality of VA outcomes and sustained
      government subsidy to provide access to affordable modern cataract surgery are
      needed.

PMID- 19406377
TI  - Peripapillary retinal nerve fiber layer thinning in patients with autosomal
      recessive cone-rod dystrophy.
AB  - PURPOSE: To evaluate peripapillary retinal nerve fiber layer (RNFL) thickness
      using spectral-domain optical coherence tomography in patients with autosomal
      recessive cone-rod dystrophy (CRD). DESIGN: Cross-sectional study. METHODS:
      Eleven patients (22 eyes) with CRD were studied, including 4 patients with
      identified ABCA4 gene mutations. Peripapillary RNFL thickness was measured in 16
      segments from 4 quadrants. The analyses were based on age and disc size-adjusted
      normative data. An abnormal thinning was considered when RNFL thickness
      measurements were less than the fifth percentile in at least 2 of 4 segments in a
      quadrant. Mean RNFL thickness was compared quantitatively with normative data
      obtained from 134 subjects. RESULTS: Eight patients (73%) had peripapillary RNFL
      thinning in at least 1 quadrant of at least 1 eye, including 3 of 4 patients with
      known ABCA4 gene mutations. Peripapillary RNFL thinning in the temporal quadrant
      was seen most commonly in 11 (79%) of 14 eyes with thinning in at least 1
      quadrant. Significant thinning of the overall peripapillary RNFL was observed in
      CRD patients compared with controls (P = .0002). Subgroup analysis showed that 8
      (89%) of 9 patients who were older than 40 years had thinning in at least 1
      quadrant of at least 1 eye. CONCLUSIONS: Peripapillary RNFL thinning was observed
      commonly in our patients with autosomal recessive CRD. The results confirm that
      the inner retinal structures can be affected in outer retinal disease. Careful
      evaluation of the inner retina may be important in determining the success rate
      of potential treatments for predominantly outer retinal diseases.

PMID- 19406380
TI  - Shifts in sensory dominance between various stages of user-product interactions.
AB  - In the area of product design, sensory dominance can be defined as the relative
      importance of different sensory modalities for product experience. It is often
      assumed that vision dominates the other senses. In the present study, we asked
      243 participants to describe their experiences with consumer products in various
      situations: while buying a product, after the first week, the first month, and
      the first year of usage. The data suggest that the dominant sensory modality
      depends on the period of product usage. At the moment of buying, vision is the
      most important modality, but during the usage the other sensory modalities gain
      importance. The roles of the different modalities during usage are product
      dependent. Averaged over 93 products analyzed in this study, after one month of
      usage touch becomes more important than vision, and after one year vision, touch
      and audition appear to be equally important. We conclude that to create a long
      lasting positive product experience, designers need to consider user-product
      interaction at different stages of product usage and to determine which sensory
      modality dominates product experience at each stage.

PMID- 19406381
TI  - Analysis of gene expression profiles in human periodontal ligament cells under
      hypoxia: the protective effect of CC chemokine ligand 2 to oxygen shortage.
AB  - Periodontal ligament (PDL) cells appear to play important functional roles in
      response to mechanical stress. We hypothesized that hypoxia caused by a
      deformation of blood vessels and the following ischaemia may play a crucial role
      in differential gene expression in PDL cells affected by mechanical stress. Gene
      induction in cultured human PDL cells by hypoxia was analyzed using cDNA array,
      followed by RT-PCR analysis. Eleven hypoxia-responsive genes were found
      differentially expressed under low-oxygen conditions in PDL cells. Among them,
      CCR2, CC chemokine ligand 2 (CCL2) receptor was studied in more detail since
      little information is available on the role of chemokines in adaptive responses
      of PDL cells under hypoxia. Here we investigate whether CCR2 mediates the
      signalling to maintain the homeostasis of PDL cells. We found that cell death of
      PDL cells was induced under hypoxia with down-regulation of CCL2 mRNA expression.
      However, the exogenous CCL2 prevented PDL cell death under oxygen shortage with
      the increment of cellular inhibitor of apoptosis (cIAP) mRNA expression. The
      present study demonstrated substantial effects of hypoxia on gene expression of
      CCL2 and CCR2 in PDL cells, indicating that mechanical loading accompanied with
      mild hypoxia allows PDL cells to elicit adaptive responses with up-regulation of
      CCR2.

PMID- 19406382
TI  - [Late recurrence of a retroperitoneal abscess due to actinomycosis].

PMID- 19406383
TI  - [Hemosuccus pancreaticus syndrome].

PMID- 19406384
TI  - [Iatrogenic pneumothorax caused by intrathoracic migration of osteosynthesis
      material].

PMID- 19406385
TI  - [Hepatic epithelioid haemangioendothelioma presenting as hepatic hydatidosis].

PMID- 19406386
TI  - [Endosalpingiosis of the appendix].

PMID- 19406387
TI  - [Thrombosis of the inferior vena cava: a rare complication after laparoscopic
      splenectomy].

PMID- 19406388
TI  - [Concurrent splenic tumour and pancreatic cystic neoplasm. A confusing lesion].

PMID- 19406389
TI  - [Breast fibroadenomas may also contain premalignant and malignant lesions].

PMID- 19406390
TI  - [Schistosomiasis as a cause of acute appendicitis].

PMID- 19406391
TI  - [Silicone-induced lymphadenitis: a possible false positive of malignancy].

PMID- 19406392
TI  - [Saccular renal artery aneurysm].

PMID- 19406393
TI  - 2D image registration using focused mutual information for application in
      dentistry.
AB  - Spatial alignment of image data is a common task in computer vision and medical
      imaging. This should preferentially be done with minimal intervention of an
      operator. Similarity measures with origin in the information theory such as
      mutual information (MI) have proven to be robust registration criteria for this
      purpose. Intra-oral radiographs can be considered images of piecewise rigid
      objects. Teeth and jaws are rigid but can be displaced with respect to each
      other. Therefore MI criteria combined with affine deformations tend to fail, when
      teeth and jaws move with respect to each other between image acquisitions. In
      this paper, we consider a focused weighing of pixels in the reference image. The
      resulting criterion, focused mutual information (FMI) is an adequate tool for the
      registration of rigid parts of a scene. We also show that the use of FMI is more
      robust for the subtraction of lateral radiographs of teeth, than MI confined to a
      region of interest. Furthermore, the criterion allows the follow-up of small
      carious lesions when upper and lower jaw moved between the acquisition of test
      and reference image.

PMID- 19406394
TI  - Social disadvantage, air pollution, and asthma physician visits in Toronto,
      Canada.
AB  - BACKGROUND: Previous research demonstrates that ambient air pollution exacerbates
      asthma. Asthma morbidity also varies with socioeconomic position (SEP). Few
      studies have examined if ambient air pollution has a differential impact on
      income subgroups of the population. This paper investigates socioeconomic
      variation in ambulatory physician consultations for asthma and assesses possible
      effect modification of SEP on the association between physician visits and air
      pollution for children aged 1-17 and adults aged 18-64 in Toronto, Canada,
      between 1992 and 2001. METHODS: Generalized additive models and generalized
      linear models were used to estimate the adjusted risk of asthma physician visits
      associated with an interquartile range increase in sulfur dioxide (SO2), nitrogen
      dioxide (NO2), particulate matter (PM2.5), and ozone (O3). RESULTS: A
      socioeconomic gradient in the number of physician visits was observed among
      children and adults and both sexes. SO2, NO2, and PM2.5 had positive associations
      with physician visits. The risk ratios for the low socioeconomic group were
      significantly greater than those for the high socioeconomic group in several of
      the models of SO2 and PM2.5. CONCLUSIONS: These findings suggest increased
      ambulatory physician visits represent another component of the public health
      impact of urban air pollution. The burden of this impact may be borne
      disproportionately by those with lower SEP. Clarifying the role of SEP in
      altering susceptibility to the effects of air pollution is essential not only to
      inform revisions of ambient air quality standards, but also to design public
      health interventions to reduce health impacts on sensitive subgroups of the
      population.

PMID- 19406395
TI  - Fertility preservation for female cancer patients: early clinical experience.
AB  - OBJECTIVE: To characterize the early experience of a clinical program designed to
      provide strategies for fertility preservation to female cancer patients about to
      undergo chemotherapy or radiation therapy. DESIGN: Retrospective chart review;
      case-control study. SETTING: Academic medical center. PATIENT(S): Sixty-five
      female cancer patients and 57 age-matched infertility patients. INTERVENTION:
      Enrollment in a program for fertility preservation. MAIN OUTCOME MEASURE(S):
      Choice of active participation, fertility preservation option selection, clinical
      outcomes of patients undergoing oocyte retrieval, attitudes regarding embryo
      disposition. RESULT(S): Of 65 patients referred to the program, 18 declined to
      undergo embryo, oocyte, or tissue cryopreservation. Six were found not to be
      eligible for medical reasons. Of the remaining 41 patients, 35 chose to
      cryopreserve embryos, four chose to cryopreserve oocytes, and two chose to
      undergo ovarian tissue freezing. Fewer oocytes were recovered from the embryo
      cryopreservation group when compared with an age-matched control group, but the
      mean number of zygotes generated was similar. Attitudes regarding embryo
      disposition were different between the two groups. No serious clinical sequelae
      resulted from participation. CONCLUSION(S): Fertility preservation techniques
      employing available technology may provide safe and practical options to female
      cancer patients facing chemotherapy or radiation therapy. A significant number of
      otherwise appropriate participants decline active management. Cancer patients
      display different attitudes regarding embryo disposition when compared with
      infertility patients without cancer.

PMID- 19406396
TI  - Conservative surgical management for diffuse uterine adenomyosis.
AB  - OBJECTIVE: To determine the effects of new conservative surgical management for
      diffuse uterine adenomyosis. DESIGN: Retrospective clinical study. SETTING:
      Gynecology department in a general hospital. PATIENT(S): A total of 44 women with
      diffuse adenomyosis. INTERVENTION(S): Conservative surgical management. MAIN
      OUTCOME MEASURE(S): Mean visual analog scale score of dysmenorrhea and
      menorrhagia after a 3-month follow-up. RESULT(S): After this surgery, the mean
      visual analog scale score of dysmenorrhea decreased from 9.4 to 0.8, and anemia
      due to menorrhagia improved in all women. Two patients became pregnant, with one
      interstitial pregnancy and one normal pregnancy that is continuing. No major
      complications or sequelae were observed. CONCLUSION(S): This procedure should be
      considered as a therapeutic option in women with symptoms of diffuse uterine
      adenomyosis who wish to avoid hysterectomy.

PMID- 19406397
TI  - Expression of angiopoietins 1, 2 and their common receptor tie-2 in relation to
      the size of endothelial lining gaps and expression of VEGF and VEGF receptors in
      idiopathic menorrhagia.
AB  - OBJECTIVE: To investigate whether idiopathic menorrhagia (IM) is associated with
      alterations of the vascular expression of angiopoietin-1, angiopoietin-2, and tie
      2 receptor. DESIGN: Prospective clinical study. SETTING: University Hospital,
      Department of Gynecology. PATIENT(S): Twenty-four patients with IM and 18 women
      with eumenorrhea. INTERVENTION(S): Endometrial samples underwent
      immunohistochemical staining for CD34, angiopoetin-1, angiopoietin-2, tie-2, and
      smooth muscle actin-alpha. Previously published data on gap size and expression
      of vascular endothelial growth factor family members were used. MAIN OUTCOME
      MEASURE(S): Differences in immunostaining for these markers by computer-assisted
      stereological analysis. RESULT(S): There was significantly more angiopoetin-1
      positive vessels in IM in the secretory phase, but not of angiopoetin-2 and tie
      2, compared with controls. Densities of angiopoetin-1 positive vessels correlated
      significantly to those of angiopoetin-2 and vascular endothelial growth factor
      receptor 3. Smooth muscle actin-alpha positive pericytes covered the gaps. Double
      staining for CD34 and tie-2 receptor was partly identical, but gaps were covered
      by tie-2 stain. CONCLUSION(S): The discrete deregulation observed of the
      angiopoetin-1 expression before menstruation might affect vascular integrity,
      thereby contributing to the excessive blood loss in IM.

PMID- 19406399
TI  - Submucous myomas and their implications in the pregnancy rates of patients with
      otherwise unexplained primary infertility undergoing hysteroscopic myomectomy: a
      randomized matched control study.
AB  - OBJECTIVE: To determine whether hysteroscopic myomectomy for submucous fibroids
      in women with unexplained primary infertility achieved better pregnancy rates
      than no intervention. DESIGN: Prospective randomized matched control trial.
      SETTING: Tertiary university fertility care unit. PATIENT(S): From January 1999
      to February 2006, a total of 215 women with unexplained primary infertility and
      with ultrasonographically diagnosed submucous myomas as the sole cause for
      fertility failure were recruited. INTERVENTION(S): Women were randomly allocated
      to one of two pretreatment groups matched by age. Hysteroscopic myomectomy was
      performed in the study group (n = 101). Diagnostic hysteroscopy and myoma biopsy
      was performed in the control group (n = 103). No fertility therapy was given for
      either group. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates according to
      patient and myoma characteristics. RESULT(S): The baseline characteristics of
      both patients and submucous myomas were comparable. Among patients with complete
      follow-up, a total of 93 (45.6%) pregnancies occured-64 (63.4%) in the study
      group and 29 (28.2%) in the control group. Women in the study group had a better
      possibility of becoming pregnant after hysteroscopic myomectomy with a relative
      risk of 2.1 (95% confidence interval, 1.5-2.9). No difference in pregnancy rates
      was observed according to size, number, and location of myomas in both groups.
      However, fertility rates appeared to increase after hysteroscopic myomectomy of
      type 0 and type I myomas (P < 0.05). In contrast, for the subgroup of patients
      with type II myomas, no difference in fertility rates were noted. CONCLUSION(S):
      Hysteroscopic myomectomy for submucous fibroids in women with unexplained primary
      infertility is effective in achieving a better pregnancy rate. We think that a
      multicenter study should be conducted before evaluating the impact of submucous
      myoma characteristics on fertility outcome.

PMID- 19406398
TI  - A cost-effectiveness comparison of embryo donation with oocyte donation.
AB  - OBJECTIVE: To compare the cost-effectiveness of embryo donation (ED) to that of
      oocyte donation (OD). DESIGN: Calculation of cost-effectiveness ratios (costs per
      outcome achieved) using data derived from clinical practices. SETTING: In vitro
      fertilization centers and embryo donation programs. PATIENT(S): Infertile couples
      undergoing oocyte donation or embryo donation. INTERVENTION(S): Oocyte donation
      or embryo donation cycles. MAIN OUTCOME MEASURE(S): Cost-effectiveness ratios.
      RESULT(S): For a single cycle, ED is approximately twice as cost-effective as OD,
      with a cost-effectiveness ratio of $21,990 per live delivery compared to 40,600
      dollars. When strategies of up to three cycles (to achieve one live delivery) are
      used, ED costs 13,505 dollars per live delivery compared to 31,349 dollars for
      OD. CONCLUSION(S): Cost-effectiveness is a compelling reason for infertile
      couples to consider embryo donation.

PMID- 19406400
TI  - An interrater reliability study of the assessment of pressure ulcer risk using
      the Braden scale and the classification of pressure ulcers in a home care
      setting.
AB  - BACKGROUND: Measurement error can seriously affect the validity of pressure ulcer
      risk assessment and of pressure ulcer classification. OBJECTIVES: Determination
      of interrater reliability and agreement of pressure ulcer risk and pressure
      ulcers using the Braden scale and the EPUAP system. DESIGN AND SETTING: Duplicate
      assessments by trained nurses during two nationwide pressure ulcer prevalence
      surveys in the years 2007 and 2008 in The Netherlands in the home care setting.
      PARTICIPANTS: Home care clients which participated in 2007 (n=352) and 2008
      (n=339) in the pressure ulcer prevalence surveys. METHODS: The Braden scale was
      used to assess pressure ulcer risk. Skin examination was conducted to detect
      pressure related tissue damages and to classify them according to the EPUAP.
      RESULTS: In 2007 and 2008, Intraclass Correlation Coefficients for Braden scale
      sum scores were 0.90 (95% CI: 0.88-0.92) and 0.88 (95% CI: 0.85-0.91)
      respectively, and corresponding Standard Errors of Measurement were 1.00 and
      0.98. 95% limits of agreement were -2.8 to 2.8 and -2.7 to 2.7 respectively. The
      items "moisture", "sensory perception" and "nutrition" contained largest amounts
      of measurement error. Proportions of agreement for the classification of pressure
      ulcers were 96% and interrater reliability was 0.81 and 0.79. Most disagreements
      were observed for the classification of grade 1 pressure ulcers. CONCLUSIONS: The
      standardized study procedure applied in the annual nationwide pressure ulcer
      prevalence surveys leads to reliable and reproducible results regarding pressure
      ulcer risk and pressure ulcer prevalence in the home care setting. Researchers
      and practitioners should be careful when drawing inferences from single pressure
      ulcer risk factors included in the Braden scale. Descriptions of the items
      "moisture", "sensory perception" and "nutrition" should be made more clearly and
      unambiguous.

PMID- 19406401
TI  - Coronary sinus concentrations of interleukin 6 and its soluble receptors are
      affected by reperfusion and may portend complications in patients with myocardial
      infarction.
AB  - Interleukin 6 (IL-6) is a pleiotropic cytokine involved in both inflammatory
      reaction and myocardial response to stress. Its effects largely depend on the
      concentration of the soluble receptors (sIL-6R and sgp130). We investigated the
      production of IL-6, sIL-6R and sgp130 by the heart during ischemia and
      reperfusion. METHODS: The levels of IL-6 were determined in blood of 34 patients
      with first myocardial infarction (STEMI), left anterior descending (LAD) artery
      occlusion, otherwise normal coronaries, without significant co-morbidities and 16
      comparable subjects with stable ischemic heart disease and lesion in LAD. Blood
      samples from coronary sinus (CS) and aorta (Ao) were drawn before percutaneous
      intervention (PCI), immediately after and at the end of the procedure. Venous
      blood from 30 healthy volunteers served as control. RESULTS: STEMI patients
      presented high IL-6 concentrations that increased further after reperfusion when
      its levels in CS became significantly higher than in Ao. In both groups prior to
      the PCI there were significantly higher concentrations of sIL-6R in Ao than in
      CS. This difference disappeared immediately after reperfusion. STEMI patients who
      experienced cardiovascular complications had higher IL-6 concentration and higher
      transcardiac sIL-6R gradient than patients with event-free hospitalisation. This
      association was confirmed in multivariate logistic regression analysis.
      Myocardial infarction increases concentration of IL-6 that is further elevated by
      reperfusion. A transcardiac gradient of sIL-6R during ischemia may indicate that
      large amounts of soluble IL-6 receptors are bound to the infarcted heart and thus
      affect signal transduction. IL-6 and initial sIL-6R gradient may portend
      complications in STEMI patients.

PMID- 19406402
TI  - Short-term 20-mg atorvastatin therapy reduces key inflammatory factors including
      c-Jun N-terminal kinase and dendritic cells and matrix metalloproteinase
      expression in human abdominal aortic aneurysmal wall.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) accumulates features of a chronic
      inflammatory disorder and irreversible destruction of connective tissue. A recent
      experimental study identified c-Jun N terminal kinase (JNK) as a proximal
      signaling molecule in the pathogenesis of AAA and vascular dendritic cells as key
      players in the inflammatory reaction and degradation of the extracellular matrix.
      Statins can inhibit cell proliferation and vascular inflammation, which might
      help prevent AAA progression. However, supporting clinical data from human
      studies are lacking. We hypothesized that atorvastatin might inhibit JNK and
      dendritic cells, resulting in suppression of inflammatory cells and matrix
      metalloproteinases (MMPs) in human tissue of AAA. METHODS: Patients with AAA were
      randomized to atorvastatin (20mg/day, n=10) and non-treated (n=10) groups. After
      treatment for 4 weeks, patients underwent abdominal aorta replacement, tissue
      specimens were obtained, and tissue composition was assessed using
      immunohistochemistry with quantitative image analysis. RESULTS: Atorvastatin
      significantly reduced expression of JNK (1.1% vs. 8.1%, P=0.0002) and dendritic
      cells (3.2 vs. 7.2, P=0.003) compared to controls. T cells (142 vs. 315,
      P=0.008), macrophages (13 vs. 24, P=0.048) and immunoreactivity to MMP-2 (7.8%
      vs. 21%, P=0.049) and MMP-9 (13% vs. 24%, P=0.028) were also suppressed in the
      atorvastatin group. Serum low-density lipoprotein cholesterol level was decreased
      by 40% in the atorvastatin group. CONCLUSIONS: Atorvastatin treatment acutely
      reduces JNK expression and dendritic cells, resulting in reduced inflammatory
      cell content and expression of MMPs in the AAA wall.

PMID- 19406403
TI  - Low CD34+ cell count and metabolic syndrome synergistically increase the risk of
      adverse outcomes.
AB  - OBJECTIVES: Metabolic syndrome (MetS) associates with endothelial dysfunction and
      a high risk of cardiovascular events and death. Circulating progenitor cells have
      been shown to contribute to endothelial homeostasis and repair . We aimed to test
      whether progenitor cell count is an independent event predictor and modifies
      cardiovascular risk associated with MetS. METHODS: On the basis of the expression
      of CD34, CD133 and KDR, 6 phenotypes of progenitor cells were counted using flow
      cytometry in 214 subjects with and without MetS. We recorded classical risk
      factors and MetS components, cumulative risk estimates, and high-sensitive C
      reactive protein. Subjects were followed-up for a median of 34 months to collect
      total events, cardiovascular events and all-cause mortality. RESULTS: In the Cox
      proportional hazards regression analyses, we found that, unlike other phenotypes,
      reduced CD34+ cells predicted cardiovascular and total events and death,
      independently of all potential confounders. Remarkably, a low CD34+ cell count
      significantly increased the risk associated with MetS, as shown by synergy
      indexes. CONCLUSION: The level of circulating CD34+ cells is a novel independent
      risk biomarker and modulates outcomes in the MetS, suggesting that generic
      progenitor cells have a role in disease development or progression over the long
      term.

PMID- 19406404
TI  - Simulation of extension, radial and ulnar deviation of the wrist with a rigid
      body spring model.
AB  - A novel computational model of the wrist that predicts carpal bone motion was
      developed in order to investigate the complex kinematics of the human wrist. This
      rigid body spring model (RBSM) of the wrist was built using surface models of the
      eight carpal bones, the bases of the five metacarpal bones, and the distal parts
      of the ulna and radius, all obtained from computed tomography (CT) scans of a
      cadaver upper limb. Elastic contact conditions between the rigid bodies modeled
      the influence of the cartilage layers, and ligamentous structures were
      constructed using nonlinear, tension-only spring elements. Motion of the wrist
      was simulated by applying forces to the tendons of the five main wrist muscles
      modeled. Three wrist motions were simulated: extension, ulnar deviation and
      radial deviation. The model was tested and tuned by comparing the simulated
      displacement and orientation of the carpal bones with previously obtained CT
      scans of the same cadaver arm in deviated (45 degrees ulnar and 15 degrees
      radial), and extended (57 degrees ) wrist positions. Simulation results for the
      scaphoid, lunate, capitate, hamate and triquetrum are presented here and provide
      credible prediction of carpal bone movement. These are the first reported results
      of such a model. They indicate promise that this model will assist in future
      wrist kinematics investigations. However, further optimization and validation are
      required to define and guarantee the validity of results.

PMID- 19406405
TI  - Combination of 1H nuclear magnetic resonance spectroscopy and mass spectrometry
      as tools for investigation of the thermolytic and solvolytic effects Case of
      carbamates analysis.
AB  - The carbamate pesticides are a well known thermo-sensible compound class. Under
      unfavourable conditions, these compounds are highly prone to degradation via
      fragmentation and/or rearrangement mechanisms. Their transformation processes are
      observed in consequence of two factors: structure with fragile bonds on the one
      hand and a stressing environment on the other hand leading to a difficult direct
      gas chromatography (GC) analysis, i.e. without derivatisation. In this paper, we
      investigated an original methodology based on the complementarity of analysis by
      proton nuclear magnetic resonance spectroscopy ((1)H NMR) and those provided by
      GC hyphenated with ion-trap mass selective detection (GC-ITMS) to investigate
      combined effects of temperature and solvent nature affecting the behaviour of 16
      carbamates. Among tested solvents, toluene and acetonitrile with 0.1% acetic acid
      were considered as the best solvents for storage and GC analysis respectively.
      Carbaryl, chlorpropham, carbofuran and N-sulfenylated compounds began to be
      thermodegraded with a loss equal to 1-5% even at 50 degrees C. An on-column
      injection validated as providing no degradation was used to analyse the identical
      solution that in (1)H NMR and it was emphasised that results of the measured
      degradation rates were identical at +/-2%. It was highlighted that this
      methodology was extensible to study mechanisms and parameters with other
      (bio)molecules.

PMID- 19406406
TI  - On-column injection system for use of large diameter inside needle capillary
      adsorption trap devices.
AB  - Direct coupling of the needle trap to the capillary column in the split/splitless
      gas chromatographic (GC) inlet with simple modification facilitates full
      exploitation of the column efficiency, even when using the large volume trap
      filled with 35 mg of Tenax TA. A schematic diagram of the inlet and of the new
      modification of the INCAT device and an example of BTEX (benzene, toluene,
      ethylbenzene and xylenes) analysis is presented. Determination of the
      repeatability of BTEX analyses resulted in relative standard deviations of 2.4
      3.6%.

PMID- 19406407
TI  - Newly identified degradation products of ceftiofur and cephapirin impact the
      analytical approach for quantitative analysis of kidney.
AB  - This paper describes our research on the degradation of ceftiofur and cephapirin
      at physiological temperatures in kidney extract and in alkaline and acidic
      solution, conditions that regularly occur during sample preparation. Degradation
      products were identified using LC-ToF/MS, NMR and microbiological techniques.
      Additionally kinetics of the degradation processes were studied. A slight
      instability of cephapirin and desfuroylceftiofur was observed at elevated
      temperatures. Ceftiofur and cephapirin degraded immediately and completely in an
      alkaline environment, resulting in inactive degradation products. Ceftiofur and
      cephapirin also degraded immediately and completely in kidney extract resulting
      in both formerly reported metabolites as well as not previously reported
      products. Our research shows that conditions often occurring during the analysis
      of ceftiofur or cephapirin result in rapid degradation of both compounds. From
      this it is concluded that underestimation of the determined amounts of ceftiofur
      and cephapirin is likely to occur. Therefore, a new approach is needed for the
      analysis of both compounds newly identified degradation products.

PMID- 19406408
TI  - Preparation of a new crown ether-based chiral stationary phase containing
      thioester linkage for the liquid chromatographic separation of enantiomers.
AB  - A new chiral stationary phase (CSP) containing thioester linkages was prepared by
      bonding (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid to mercaptopropylsilica
      gel. The chiral recognition ability of the new CSP was found to be greater than
      that of the previously reported CSP containing amide linkages in the resolution
      of the various alpha-amino acids that were tested, except for that of Met, Ser
      and Thr. In the resolution of racemic amines and amino alcohols, the new CSP was
      always better than the one containing amide linkages in terms of the separation
      factors (alpha) and the resolutions (RS). Given the identical elution orders on
      the two CSPs, it was concluded that the chiral recognition mechanism is not
      affected by the change of the linkage type. In addition, the new CSP was found to
      be quite stable under the acidic mobile phase conditions that were utilized,
      indicating that the thioester linkage is useful as a tethering group.

PMID- 19406409
TI  - Residue depletion of albendazole and its metabolites in the muscle tissue of
      large mouth and hybrid striped bass after oral administration.
AB  - The residue depletion profiles of albendazole (ABZ) and its major metabolites:
      albendazole sulfoxide (ABZ-SO), albendazole sulfone (ABZ-SO(2)) and albendazole
      aminosulfone (ABZ-2-NH(2)SO(2)) were studied in the muscle tissues of large mouth
      (LMB) and hybrid striped bass (HSB). A single oral dose of 10mg/kg albendazole
      was given to the two fish species via intra-gastric tube. The muscle tissues with
      adhering skin were collected at 8, 16, 24, 48, 72, 96 and 120h post dose from
      both species. The samples were homogenized in dry ice and subjected to extraction
      and cleanup procedures. The final sample extracts were analyzed by high
      performance liquid chromatography. The results indicate that both ABZ and its
      pharmacologically active metabolite ABZ-SO were retained longer in LMB than in
      HSB after oral treatment. Albendazole was detectable until 8h or 6.7 degree days
      ( degrees D) and 48h (40 degrees D) in HSB and LMB, respectively. However, ABZ-SO
      was detectable up to 48h (40 degrees D) and 96h (80 degrees D) in HSB and LMB,
      respectively. Among the inactive metabolites, ABZ-SO(2) was present in both fish
      species; however, ABZ-2-NH(2)SO(2) was detected only in LMB.

PMID- 19406410
TI  - Determination of thyreostats in urine and thyroid gland by ultra high performance
      liquid chromatography tandem mass spectrometry.
AB  - Thyreostatic compounds could be illegally administered to animals in order to
      obtain a weight gain due to a higher retention of water in the edible tissue and
      the gastro-intestinal tract. In the European Union their use for animal
      production is banned since 1981. Recently a highly sensitive method exploiting
      the determination of thyreostats with 3-iodobenzylbromide prior to purification
      to determine thyreostats in urine and other matrices was reported. For the first
      time, the UPLC instrumentation was used to separate the 3-iodobenzyl derivatives
      of various thyreostats. The deuterated internal standards tapazole-d(3) and
      propylthiouracil-d(5) were for the first time used for the quantification of
      tapazole, thiouracil, methylthiouracil, propylthiouracil, phenylthiouracil and
      mercaptobenzimidazole. The confirmative quantitative liquid chromatographic
      tandem mass spectrometric (LC-MS/MS) method was validated according to Commission
      Decision 2002/657/EC. The decision limit (CCalpha) and the detection capability
      (CCbeta) were found to be for all compounds below the recommended value of 10
      microg kg(-1).

PMID- 19406411
TI  - A quest for the optimal additive in chiral preparative chromatography.
AB  - Traditionally, the choice of acid/base additives used in chiral preparative
      chromatography has not been considered very important. However, it was recently
      demonstrated that strongly adsorbing additives can result in the most unexpected
      enantiomer band shapes in modern chiral preparative chromatographic systems. In
      the present study we demonstrate that, depending on the choice of additive, it is
      actually possible to obtain the following four binary band-shape compositions
      when a racemic mixture is injected: (i) anti-Langmuir/anti-Langmuir, (ii) anti
      Langmuir/Langmuir, (iii) Langmuir/Langmuir and (iv) Langmuir/anti-Langmuir.
      Further, we made an advanced numerical investigation, in order to ascertain which
      one of the four band-shape compositions, is the most favourable one in
      preparative batch chromatography of a racemic mixture. We found that if the
      target for purification is either the first eluting enantiomer or both ones, the
      traditional Langmuir/Langmuir band-shape composition should be chosen. But, if
      only the second eluting enantiomer is to be purified the optimal situation is the
      anti-Langmuir/Langmuir band-shape composition. Thus, it was concluded that the
      best choice of additive depends on which enantiomer is of interest and it is
      useful to perform a thorough additive screening to find the optimal additive,
      giving the most advantageous peak shape composition and accordingly the best
      process performance for a particular separation problem.

PMID- 19406412
TI  - Multi-residue screening of veterinary drugs in egg, fish and meat using high
      resolution liquid chromatography accurate mass time-of-flight mass spectrometry.
AB  - The last 2 years multi-compound methods are gaining ground as screening methods.
      In this study a high-resolution liquid chromatography combined with time-of
      flight mass spectrometry (HRLC-ToF-MS) is tested for the screening of about 100
      veterinary drugs in three matrices, meat, fish and egg. While the results are
      satisfactory for 70-90% of the veterinary drugs, a more efficient sample
      preparation or extract purification is required for quantitative analysis of all
      analytes in more difficult matrices like egg. The average mass measurement error
      of the ToF-MS for the veterinary drugs spiked at concentrations ranging from 4 to
      400 microg/kg, is 3.0 ppm (median 2.5 ppm) with little difference between the
      three matrices, but slightly decreases with increasing concentration. The
      SigmaFit value, a new feature for isotope pattern matching, also decreases with
      increasing concentration and, in addition, shows an increase with increasing
      matrix complexity. While the average SigmaFit value is 0.04, the median is 0.01
      indicating some high individual deviations. As with the mass measurement error,
      the highest deviations are found in those regions of the chromatogram where most
      compounds elute from the column, be it analytes or matrix compounds. The median
      repeatability of the method ranges from 8% to 15%, decreasing with increasing
      concentration, while the median reproducibility ranges from 15% to 20% with
      little difference between matrices and concentrations. The median accuracy is in
      between 70% and 100% with a few compounds showing higher values due to matrix
      interference. The squared regression coefficient is >0.99 for 92% of the
      compounds showing a good overall linearity for most compounds. The detection
      capability, CCbeta, is within 2 times the associated validation level for >90% of
      the compounds studied. By changing a few conditions in the analyses protocol and
      analysing a number of blank samples, it was determined that the method is robust
      as well as specific. Finally, an alternative validation strategy is proposed and
      tested for screening methods. While the results calculated for repeatability,
      within-lab reproducibility and CCbeta show a good comparison for the matrices
      meat and fish, and a reasonable comparison for the matrix egg, only 27 analyses
      are required to obtain these results versus 63 analysis in the traditional,
      2002/657/EC, approach. This alternative is suggested as a cost-effective
      validation procedure for screening methods.

PMID- 19406413
TI  - Compensation for matrix effects in gas chromatography-tandem mass spectrometry
      using a single point standard addition.
AB  - One of the major problems in quantitative analysis of pesticide residues in food
      samples by gas chromatography-tandem mass spectrometry (GC-MS/MS) is the
      enhancement or the suppression, of the target analyte signals in matrix extracts.
      Potentially positive samples, which had previously been identified by a rapid
      screening method, were quantified using standard addition to compensate matrix
      effects. As example we performed a systematic study on the application of the
      standard addition calibration (SAC) method for the determination of 12 pesticides
      (acephate, bromopropylate, chlorpyrifos, cypermethrin, diazinon, etrimfos,
      heptenophos, iprodione, methamidophos, procymidone, tetradifon, and triadimefon)
      in two matrices (cucumber and orange) in the range of initial concentrations of
      10-200 microg kg(-1). The influence of some factors, such as the minimum number
      of standard additions used (single, two, three or four points calibration), as
      well as the known amount of analyte added to the sample, is evaluated in order to
      obtain reliable results. Accurate quantification is achieved when a single point
      SAC at 200 microg kg(-1) was used, obtaining for all the cases recoveries between
      70 and 120%. The proposed analytical approach only needs two injections per
      sample (blank and spiked extracted sample) to determine the final concentration
      of pesticide in positive samples.

PMID- 19406414
TI  - Effects of temperature on water-in-oil emulsions stabilised solely by wax
      microparticles.
AB  - The possibility of stabilising oil-water mixtures using wax particles alone is
      reported. As judged from contact angle measurements, wax particles are
      hydrophobic and act as effective emulsifiers of water-in-squalane emulsions.
      Specific differences exist depending on the chemical composition of the
      particles. The effect of temperature on emulsion stability has been explored in
      detail. If particles are pre-adsorbed to water drop interfaces by emulsification
      at room temperature, subsequent increase of temperature leads to a progressive
      increase in sedimentation and coalescence as particles melt and desorb from
      interfaces. The temperature range over which this occurs is similar to that of
      the melting range of the particles alone. If however the particles are melted
      prior to emulsification, surface-active long chain ester or acid molecules adsorb
      to freshly created interfaces giving rise to excellent stability to coalescence
      at high temperatures. Rapid cooling of these latter emulsions enhances their long
      term stability as solidification of the molten wax leads to a thickening of the
      continuous oil phase.

PMID- 19406415
TI  - Spontaneous vesicle formation with an ionic liquid amphiphile.
AB  - A simple and effective method for the formation of stable multilamellar vesicles
      is reported as a potential application of ionic liquid materials (IL's) and as
      replacements for conventional surfactants used in such applications. The
      methodology is based on the various approaches for the formation of vesicles from
      oppositely charged surfactants. Photon correlation spectroscopy (PCS) and
      transmission electron microscopy (TEM) have been used to estimate the size of the
      aggregates; the TEM studies have also revealed morphological differences in the
      self-assembled systems with changing ionic liquid material. Size measurements
      from PCS indicate consistent growth of the ionic-liquid containing vesicles with
      increasing concentration of added anionic surfactant. 2D NOESY NMR spectroscopy
      have been used to examine the manner in which IL amphiphile self-assembles with
      the second surfactant in solution. A comparison has been made between the
      aggregates formed from hexylpyridinium tetrafluoroborate ([HexPy][BF4-])/sodium
      dodecylsulfate (SDS) and hexylpyridinium bromide ([HexPy][Br])/sodium
      dodecylsulfate (SDS).

PMID- 19406417
TI  - Modification of a reverse microemulsion with a fluorinated triblock copolymer.
AB  - A w/o microemulsion consisting of n-decane, AOT, and water with a droplet volume
      fraction Phi=0.2 and a molar ratio of water to AOT omega=40 has been used as a
      model system to investigate the effect of added amphiphilic triblock copolymers
      on structure and conductivity of the system. Structure of the system is
      determined by small-angle X-ray scattering. Conductivity is measured in a wide
      frequency and temperature range. The pure microemulsion displays the known
      phenomenon of conductivity increase with temperature at the percolation
      temperature T(p). Droplets are found to decrease in size in the same temperature
      range. The triblock copolymer poly(perfluorohexylethyl methacrylate)-b
      poly(ethylene oxide)-b-poly(perfluorohexylethyl methacrylate) has been added to
      the microemulsion such that the number of polymers per droplet z is between 0.5
      and 2. The polymer dissolves in the microemulsion and is located in the droplet.
      Microemulsion droplets deform continuously from spherical to prolate ellipsoidal
      shape with increasing polymer content. Furthermore, a strong shift of T(p) to
      higher T with increasing polymer content is observed. For z > or = 1.5 DeltaT(p)
      is nearly constant. Besides the confinement effect the specific interaction of
      the polymer blocks with the surfactant layer are of importance.

PMID- 19406416
TI  - Removal of phosphate from water by a Fe-Mn binary oxide adsorbent.
AB  - Phosphate removal is important in the control of eutrophication of water bodies
      and adsorption is one of the promising approaches for this purpose. A Fe-Mn
      binary oxide adsorbent with a Fe/Mn molar ratio of 6:1 for phosphate removal was
      synthesized by a simultaneous oxidation and coprecipitation process. Laboratory
      experiments were carried out to investigate adsorption kinetics and equilibrium,
      in batch mode. The effects of different experimental parameters, namely contact
      time, initial phosphate concentration, solution pH, and ionic strength on the
      phosphate adsorption were investigated. The adsorption data were analyzed by both
      Freundlich and Langmuir isotherm models and the data were well fit by the
      Freundlich isotherm model. Kinetic data correlated well with the pseudo-second
      order kinetic model, suggesting that the adsorption process might be chemical
      sorption. The maximal adsorption capacity was 36 mg/g at pH 5.6. The phosphate
      adsorption was highly pH dependent. The effects of anions such as Cl(-),SO42-,
      and CO32- on phosphate removal were also investigated. The results suggest that
      the presence of these ions had no significant effect on phosphate removal. The
      phosphate removal was mainly achieved by the replacement of surface hydroxyl
      groups by the phosphate species and formation of inner-sphere surface complexes
      at the water/oxide interface. In addition, the adsorbed phosphate ions can be
      effectively desorbed by dilute NaOH solutions. This adsorbent, with large
      adsorption capacity and high selectivity, is therefore a very promising adsorbent
      for the removal of phosphate ions from aqueous solutions.

PMID- 19406418
TI  - pH- and thermo-responsive dispersion of single-walled carbon nanotubes modified
      with poly(N-isopropylacrylamide-co-acrylic acid).
AB  - Single-walled carbon nanotubes (SWNTs) were homogeneously dispersed in the
      aqueous solution of poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAm-co-AA))
      with the assistance of sonification as evidenced by UV-vis absorption
      spectroscopy, transmission electron microscopy, field emission scanning electron
      microscopy and atomic force microscopy, etc. In addition, the SWNTs were endowed
      with pH- and thermo-sensitivity at the same time. The SWNTs switched reversibly
      between the aggregated and the well-exfoliated states by using pH or temperature
      as a stimulus. Moreover, the factors including solvent composition while
      preparing P(NIPAm-co-AA), concentration and composition of P(NIPAm-co-AA) showed
      evident influence on the dispersing stability of SWNTs. The introduction of a
      tiny amount of acrylic acid to copolymerize with N-isopropylacrylamide could
      greatly enhance dispersing ability of SWNTs.

PMID- 19406419
TI  - Mechanism of formation of vesicle fused phospholipid monolayers on alkanethiol
      self-assembled monolayer supports.
AB  - We investigated the process of phospholipid vesicle fusion to a hydrophobic
      surface using electrochemical impedance spectroscopy (EIS) and atomic force
      microscopy (AFM). The kinetics of the fusion of dimyristoyl phosphatidylcholine
      (DMPC) vesicles to an octadecanethiol (ODT) self-assembled monolayer (SAM) was
      followed with EIS and found to be slower than previously reported observations by
      surface plasmon resonance. AFM images of the DMPC layer taken at various stages
      of completion show they are uniform with topography similar to that of the bare
      ODT SAM. The AFM was used in contact mode to scrape away a portion of a completed
      DMPC monolayer and the hole was stable for several hours. Surprisingly, the hole
      remained stable even after the temperature of the system was raised to 38 degrees
      C, well above the gel transition temperature for DMPC of 23 degrees C. We were
      unable to scrape holes in the partially completed monolayers. We conclude that in
      the early stages of monolayer growth the DMPC molecules spread across the ODT
      surface after vesicle fusion rather than remaining in dense islands. However,
      when the DMPC monolayer is complete this mobility is lost and the DMPC will not
      spread into a vacant area.

PMID- 19406420
TI  - Particulate ionomer films prepared from dispersions of crosslinked polymer
      colloids: a structure-property study.
AB  - Polymers with properties that are governed by ionic interactions in discrete
      regions are termed ionomers. This work presents a comprehensive study of polymer
      films prepared from dispersions of crosslinked poly(butadiene/methacrylic acid)
      (poly(Bd/MAA)) particles in water. We showed recently [O. Pinprayoon, R. Groves,
      B.R. Saunders, J. Colloid Interface Sci. 321 (2008) 315-322] that poly(Bd/MAA)
      particles could be considered to have a core-shell structure with a MAA-rich
      shell. The poly(Bd/MAA) dispersions used here contained added ZnO particles which
      provided a source of Zn(2+). The films were investigated using AFM, FTIR, small
      angle X-ray scattering (SAXS), dynamic mechanical thermal analysis (DMTA) and
      tensile stress vs. strain measurements. The films showed differences and
      similarities to conventional ionomers which are discussed. The FTIR data revealed
      that the Zn(2+) ions formed ionic crosslinks with the carboxylate groups (RCOO(
      )). Mechanical property studies were conducted using DMTA and stress vs. strain
      measurements. The DMTA data revealed evidence of two main phases in the systems:
      a poly(Bd)-rich phase and a poly(MAA)-rich phase. A third phase was also found;
      which was ascribed to an interphase between the particle core and shell. The SAXS
      data showed that the films were composed of distinct poly(Bd/MAA) particles,
      implying that only partial coalescence occurred across the particle interfaces
      during formation of these particulate ionomer films. Ionic crosslinking of the
      particles was suggested to occur in the interfacial region (knit regions). The
      SAXS data also showed scattering from Zn(2+)(RCOO(-)) ionic-aggregates. These
      ionic aggregates had an average separation of 2.9 nm, which is much smaller than
      that for conventional ionomers. Interestingly, the concentration of these
      aggregates passed through a maximum and decreased as the degree of neutralisation
      of the MAA groups approached 100%. A conceptual model for the structure of these
      unconventional ionomers is discussed.

PMID- 19406421
TI  - Selective immobilization of proteins on gold dot arrays and characterization
      using chemical force microscopy.
AB  - Streptavidin that has four binding sites arranged in two opposing pairs is known
      as one of the most important linker proteins for binding the second biotinylated
      protein. To efficiently locate streptavidins to selective positions without
      nonspecific binding, we prepared well-controlled arrays of biotins on a gold
      surface by using a mixed self-assembly process. Two thiol derivatives (11
      mercapto-1-undecanol and 11-mercaptoundecanoic-(8-biotinylamido-3,6
      dioxaoctyl)amide) were used for preparing the mixed self-assembled monolayers.
      Fragment antibodies modified with biotin were immobilized on a gold surface
      covered with streptavidin. This system was applied to gold dot arrays formed by
      nanosphere lithography. The gold dot arrays were used as the mother structure to
      construct the array of proteins at the nanometer scale. Selective immobilization
      of antibodies was characterized by imaging the substrate with an atomic force
      microscope and measuring the interaction force between biomaterials by chemical
      force microscopy. Also, the interaction force between antibodies was compared
      with the force predicted using the Johnson-Kendall-Roberts theory.

PMID- 19406422
TI  - In situ preparation and luminescent properties of LaPO4:Ce3+, Tb3+ nanoparticles
      and transparent LaPO4:Ce3+, Tb3+/PMMA nanocomposite.
AB  - LaPO(4):Ce(3+), Tb(3+) nanoparticles were prepared by the reverse microemulsion
      with functional monomer, methyl methacrylate (MMA) as oil phase, and
      LaPO(4):Ce(3+), Tb(3+)/poly(methyl methacrylate) (PMMA) nanocomposite was
      obtained via polymerization of MMA monomer. The nanoparticles and nanocomposite
      have been well characterized by XRD, SEM, TEM, UV/vis spectrum, photoluminescence
      excitation and emission spectra and luminescence decays. The obtained solid
      nanocomposite LaPO(4):Ce(3+), Tb(3+)/PMMA is highly transparent and exhibits
      strong green photoluminescence upon UV excitation, due to the integration of
      luminescent LaPO(4):Ce(3+), Tb(3+) nanoparticles. The luminescent lifetime of
      Tb(3+) is determined to be 1.25 ms in the nanocomposite.

PMID- 19406424
TI  - Characterization and structural investigation of fractal porous-silica over an
      extremely wide scale range of pore size.
AB  - We have succeeded in creating Menger sponge-like fractal body, i.e., porous
      silica samples with Menger sponge-like fractal geometries, by a novel template
      method utilizing template particles of alkylketene dimer (AKD) and a sol-gel
      synthesis of tetramethyl orthosilicate (TMOS). We report here the first
      experimental results on characterization and structural investigations of the
      fractal porous-silica samples prepared with various conditions such as
      calcination temperature and packing condition of the template particles. In order
      to characterize the fractal porous-silica samples, pore volume distribution,
      porosity and specific surface area were measured over an extremely wide scale
      from 1 nm to 100 microm by means of mercury porosimetry, (1)H NMR cryoporometry,
      nitrogen gas adsorption experiments together with direct evaluations of cross
      sectional fractal dimension D(cs), and size limits of D(cs). We have found that
      the pore volume distribution and specific surface area of the fractal porous
      silica samples can be discussed in terms of different fractal porous structures
      at different scale regions.

PMID- 19406423
TI  - Direct observation of bacterial deposition onto clean and organic-fouled
      polyamide membranes.
AB  - Nanofiltration (NF) and reverse osmosis (RO) membranes are commonly applied to
      produce highly purified water from municipal wastewater effluents. In these
      applications, biofouling limits overall process performance and increases the
      cost of operation. Initial bacteria adhesion onto a membrane surface is a
      critical early step in the overall process of membrane biofouling. However,
      adsorption of effluent organic matter onto the membrane may precede bacterial
      deposition and change membrane surface properties. Herein we employed direct
      microscopic observation to elucidate mechanisms governing bacterial cell
      deposition onto clean and organic-fouled NF and RO membranes. Bovine serum
      albumin (BSA) and alginic acid (AA) were used as models for protein and
      polysaccharide rich organic matter in secondary wastewater effluents. In all
      experiments, organic fouling increased membrane hydraulic resistance and salt
      rejection, in addition to interfacial hydrophilicity and roughness. Even though
      surface hydrophilicity increased, the rougher surfaces presented by organic
      fouled membranes produced nano-scale features that promoted localized bacterial
      deposition. An extended DLVO analysis of bacterial cells and membrane surface
      properties suggested that bacterial deposition correlated most strongly with the
      Lewis acid-base free energy of adhesion and root mean square (RMS) roughness,
      whereas van der Waals and electrostatic free energies were weakly correlated.
      This was true for both clean and organic-fouled membranes. Bacterial deposition
      rates were clearly influenced by an antagonistic interplay between macroscopic
      surface hydrophilicity and nano-scale surface roughness.

PMID- 19406425
TI  - Rheological characterization of poly(ethylene oxide) solutions of different
      molecular weights.
AB  - The rheological properties of aqueous solutions of poly(ethylene oxide) (PEO) of
      different molecular weights (1x10(5), 4x10(5), 1x10(6) and 4x10(6) g mol(-1)) and
      concentrations were investigated using shear viscosity and dynamic rheological
      measurements. It was found that the aqueous solutions of PEO do not exhibit a
      yield stress and that, above a critical shear rate, all PEO solutions exhibit
      shear-thinning behavior, well described by the Cross model, except for the
      solutions made by the lowest molecular weight (1x10(5) g mol(-1)) which were
      almost Newtonian. The parameters of the Cross model, namely the zero-shear rate
      viscosity and reciprocal of the time constant, allowed the determination of the
      critical concentrations c(*) and c(**) (respectively, the transition to semi
      dilute network solution and concentrated solution). At concentrations higher than
      c(**) and below a critical shear rate, solutions made of PEO of high molecular
      weight exhibited a clearly shear-thickening behavior at very low shear rates. In
      addition, the dynamic tests showed that PEO solutions exhibit concentration
      dependent viscoelastic properties, with a dominant viscous behavior at PEO
      concentrations lower than c(**) and a dominant elastic behavior at PEO
      concentrations greater than c(**).

PMID- 19406426
TI  - The simple and facile methods to improve dispersion stability of nanoparticles:
      different chain length alkylcarboxylate mixtures.
AB  - The dispersion stability of the Ag nanoparticles with a mixed surfactant of
      alkylcarboxylates was quantitatively examined, compared with those of the Ag
      nanoparticles with a single molecule surfactant of alkylcarboxylates. The
      nanoparticles with a mixed surfactants have far-improved dispersion stability
      compared with those with normal alkylcarboxylates. The surface roughness of the
      surfactant layer might be responsible for the improved dispersion stability
      through the enhanced solvent-surfactant interaction and the decrease in inter
      particle surfactant interactions.

PMID- 19406427
TI  - Motion of deformable drops through granular media and other confined geometries.
AB  - This article features recent simulation studies of the flow of emulsions
      containing deformable drops through pores, constrictions, and granular media. The
      flow is assumed to be at low Reynolds number, so that viscous forces dominate,
      and boundary-integral methods are used to determine interfacial velocities and,
      hence, track the drop motion and shapes. A single drop in a flat channel migrates
      to the channel centerplane due to deformation-induced drift, which increases its
      steady-state velocity along the channel. A drop moving towards a smaller
      interparticle constriction squeezes through the constriction if the capillary
      number (ratio of viscous deforming forces and interfacial tension forces) is
      large enough, but it becomes trapped when the capillary number is below a
      critical value. These concepts then influence the flow of an emulsion through a
      granular medium, for which the drop phase moves faster than the suspending liquid
      at large capillary numbers but slower than the suspending liquid at smaller
      capillary numbers. The permeabilities of the granular medium to both phases
      increase with increasing capillary number, due to the reduced resistance to
      squeezing of easily deformed drops, though drop breakup must also be considered
      at large capillary numbers.

PMID- 19406428
TI  - Adsorption and thermodynamic properties of the alumina-polyacrylic acid solution
      system.
AB  - Free energies of polyacrylic acid (PAA) adsorption (DeltaG( composite function))
      on an alumina (Al(2)O(3)) surface in the temperature range 15-35 degrees C were
      estimated on the basis of adsorption-desorption measurements of the inorganic
      radioactive ions (36)Cl, (45)Ca, and (55)Fe. Adsorbing polymer macromolecules
      caused the desorption process of previously adsorbed radioactive ions. The free
      energy of Ca-PAA surface complex formation (DeltaG(o)) was estimated to be close
      to the free energy of Ca(2+) ions adsorption (polymer causes about 50% desorption
      of these ions). Moreover, a free energy of polymer molecule adsorption increase
      with the increasing temperature was observed. The obtained values of DeltaG(o)
      were compared with those calculated from the adsorption data. Additionally, the
      amount of polymer adsorbed and the thicknesses of polymer adsorption layers were
      determined in the temperature range 15-35 degrees C. The changes of polymer chain
      conformation with the temperature increase are responsible for the increase of
      PAA adsorption as well as thickness of polymer adsorption layers in the studied
      temperature range.

PMID- 19406429
TI  - From polymeric "plasticine" to shape-controlled mesoporous carbon.
AB  - A soft-phase intercalating process to synthesize mesostructured plasticine by
      using amphiphilic triblock copolymer F127 as a structure-directing agent, reverse
      triblock copolymer 25R4 as an intercalating soft matter, and soluble phenolic
      resin as a carbon source is demonstrated. The "plasticine" has interlayer organic
      organic hybrid structure, which is emplastic, sticky, and able to be easily
      shaped at will. After template removal at 350 degrees C and further carbonization
      at 600 degrees C, highly ordered mesoporous polymers and carbons can be
      successively obtained with the maintenance of the original shape. The self
      supported, shape-controlled, ordered mesoporous carbon products possess high
      surface areas (495-777 m(2)/g), large pore volumes (0.32-0.47 cm(3)/g), uniform
      pore sizes (2.5-4.3 nm) in the nanoscale and hollow tremella-like morphology in
      the micronscale which may facilitate mass transportation.

PMID- 19406430
TI  - Preparation and characterization of mesoporous VO(x)-TiO2 complex oxides for the
      selective oxidation of methanol to dimethoxymethane.
AB  - Mesoporous VO(x)-TiO(2) with high surface areas were prepared using the procedure
      of evaporation-induced self-assembly combined with ammonia posttreatment. The
      samples were characterized by X-ray diffraction (XRD), laser Raman spectroscopy
      (LRS), transmission electron microscopy (TEM), N(2) adsorption, temperature
      programmed reduction (H(2)-TPR), microcalorimetry for the adsorption of NH(3),
      and isopropanol probe reaction. Their catalytic activities were evaluated for the
      reaction of selective oxidation of methanol to dimethoxymethane (DMM). It was
      found that the VO(x)-TiO(2) materials exhibited high surface areas with pore
      diameters of 4 nm. The vanadia species were highly dispersed in the VO(x)-TiO(2)
      within 30 wt% VO(x) content, evidenced by the results of XRD and LRS. The VO(x)
      TiO(2) samples exhibited both surface acidic and redox properties. The surface
      acidity was further enhanced on the addition of SO(4)2-. The catalyst SO(4)2
      /30VO(x)-TiO(2) exhibited good performance for the selective oxidation of
      methanol (57% conversion) to DMM (83% selectivity) at 423 K.

PMID- 19406431
TI  - Magnetic resonance imaging--insights into brain injury and outcomes in premature
      infants.
AB  - Preterm birth is a major public-health issue because of its increasing incidence
      combined with the frequent occurrence of subsequent behavioral, neurological, and
      psychiatric challenges faced by surviving infants. Approximately 10-15% of very
      preterm children (born<30 weeks gestational age) develop cerebral palsy, and 30
      60% of them experience cognitive impairments. These adverse outcomes are related
      to a confluence of abnormal brain development along with white (WM) and gray
      matter (GM) injury sustained during the neonatal period. It is becoming apparent
      that the extra-uterine environment during this critical period (24-40 weeks
      gestation) in brain development has a profound and long lasting impact on the
      premature infant. Magnetic resonance imaging in the neonatal period and infancy
      provides a non-invasive, "in vivo" assessment of brain development and extent of
      brain injury. This not only helps understand the extent and timing of injury but
      also identifies infants who may benefit from early intervention to minimize the
      impact of the injury. LEARNING OUTCOMES: Readers will be able to (1) appreciate
      the diverse impact of prematurity on neurodevelopmental outcome, (2) recognize
      the biological vulnerability of the developing brain in premature infants born
      between 24 and 40 weeks of gestation, (3) understand the role of magnetic
      resonance imaging (MRI) as a tool to detect abnormal development and brain injury
      in premature infants, and (4) see the potential role for novel MR imaging methods
      as biomarkers for brain development and injury in premature infants.

PMID- 19406433
TI  - Preface to the 18th annual ASHA-NIH research symposium: Neurobiological
      determinants of communication development.

PMID- 19406434
TI  - Morphological changes and virus distribution in the ileum of colostrum-deprived
      calves inoculated with non-cytopathic bovine viral diarrhoea virus genotype-1.
AB  - Eight colostrum-deprived calves were inoculated intranasally with a non
      cytopathic strain of bovine viral diarrhoea virus (BVDV) genotype-1 and killed in
      batches of two at 3, 6, 9 and 14 days post-inoculation (dpi). Two non-inoculated
      animals with similar background served as controls. All infected calves developed
      mild pyrexia and transient leucopenia due primarily to lymphopenia. Viraemia was
      correlated with body temperature and inversely related to leucocyte count. Ileal
      Peyer's patches developed mild follicular lymphoid depletion from 3dpi. This
      change was accompanied by cellular fragmentation and pyknosis, characteristic of
      apoptosis, which was most prominent from 6dpi. Lymphocyte apoptosis was confirmed
      by ultrastructural examination. Stellate cells and macrophages located in the
      lymphoid follicles were identified as infected by virus from 3dpi and the number
      of these infected cells increased until 9dpi. Fewer lymphocytes expressed BVDV
      antigen. Macrophages had morphological features consistent with activation of
      secretory and phagocytic function from 3dpi. These findings suggest that BVDV is
      only directly responsible for the destruction of a small number of lymphocytes.
      Although lymphocyte infection coincided with the onset of apoptosis, the
      intensity of infection was disproportionate to the marked depletion of gut
      associated lymphoid tissue, particularly during the early stages of this process.
      Characterization of the indirect pathogenic mechanisms involved in the lymphoid
      depletion associated with BVDV infection will require additional study.

PMID- 19406432
TI  - Modulation, adaptation, and control of orofacial pathways in healthy adults.
AB  - Although the healthy adult possesses a large repertoire of coordinative
      strategies for oromotor behaviors, a range of nonverbal, speech-like movements
      can be observed during speech. The extent of overlap among sensorimotor speech
      and nonspeech neural correlates and the role of neuromodulatory inputs generated
      during oromotor behaviors are unknown. The focus of this review is to consider
      the adaptive capacity of the orofacial substrate, and the neural correlates of
      kinematic parameter encoding at cortical and subcortical levels subserving
      oromotor behaviors. Special emphasis is directed toward distributed neural
      networks that are dynamically modulated by environment and task related demands.
      LEARNING OUTCOMES: Readers will (1) gain a better understanding of healthy adult
      orofacial pathways, (2) be able to identify orofacial pathway components that
      contribute to sensorimotor integration, and (3) better understand the flexible
      connectivity among distributed neural networks subserving oromotor behavior.

PMID- 19406435
TI  - Pulmonary myxoma in a sheep.
AB  - Pulmonary myxomas are rare in domestic animals and only two cases have been
      reported previously in sheep. An 8 x 6 x 4 cm mass was detected in the
      diaphragmatic lobe of the right lung of a 4-year-old Persian Karakul ewe. The
      mass was well demarcated, multilobulated, soft in consistency and white in
      colour. The cut surface exuded a mucoid substance and a distinct capsule was
      evident. Microscopically, the tumour comprised a hypocellular myxomatous matrix,
      rich in acid mucopolysaccharides, with scattered spindle-shaped or stellate
      cells. These cells had uniform, oval-shaped nuclei without visible nucleoli and
      expressed vimentin and S100 on immunohistochemical examination. These gross,
      microscopical and immunohistochemical features are characteristics of myxoma.

PMID- 19406436
TI  - Nationwide monitoring of nonylphenolic compounds and coprostanol in sediments
      from Korean coastal waters.

PMID- 19406437
TI  - Sediment profiles of less commonly determined elements measured by Laser Ablation
      ICP-MS.
AB  - Anthropogenic influences on trace element profiles in dated sediments from
      estuaries have been often documented, with the vast majority of studies focusing
      on a short list of high-abundance trace elements. Laser Ablation-Inductively
      Coupled Plasma-Mass Spectrometry (LA-ICP-MS) provides a new approach that
      minimizes sample preparation and contamination while yielding data on a much
      larger list of elements simultaneously. We present concentrations and enrichment
      factor profiles for 22 elements at a locality that is 50 km southeast of
      Baltimore, the principal industrial city on Chesapeake Bay. Samples representing
      deposition over almost the entire 20th century were obtained from two archived
      cores collected 20 years apart. The following elements exhibit profiles
      consistent with a strong anthropogenic influence, i.e. enrichment after 1920
      followed by decline after ca.1980, possibly reflecting increased regulatory
      efforts: Mn, Co, Cu, Zn, Ag, Cd, In, Sn, Sb, Te, Tl, Pb and Bi. As expected, the
      redox-sensitive elements: Mo, Re and U have similar profiles to one another.
      Previously, the potentially hazardous elements, Ag, In, Sb, Te, Tl and Bi, have
      been measured only rarely in estuarine sediments and never in Chesapeake Bay. Our
      discovery that their profiles track those of well-known pollutants underscores a
      need to investigate their sources, transport and biogeochemical behavior. Several
      rarely determined trace elements, Ga, Ge and Nb, exhibit trendless profiles, as
      do the major elements, Ti and Fe.

PMID- 19406438
TI  - Spatial and temporal variations in cadmium concentrations and burdens in the
      Pacific oyster (Crassostrea gigas) sampled from the Pacific north-west.
AB  - Oysters from the north-west coast of Canada contain high levels of cadmium, a
      toxic metal, in amounts that exceed food safety guidelines for international
      markets. A first required step to determine the sources of cadmium is to identify
      possible spatial and temporal trends in the accumulation of cadmium by the
      oyster. To meet this objective, rather than sample wild and cultured oysters of
      unknown age and origin, an oyster "grow-out" experiment was initiated. Cultured
      oyster seed was suspended in the water column up to a depth of 7 m and the oyster
      seed allowed to mature a period of 3 years until market size. Oysters were
      sampled bimonthly and at time of sampling, temperature, chlorophyll-a, turbidity
      and salinity were measured. Oyster total shell length, dry tissue weights,
      cadmium concentrations (microg g(-1)) and burdens (microg of cadmium oyster(-1))
      were determined. Oyster cadmium concentrations and burdens were then interpreted
      with respect to the spatial and temporal sampling design as well as to the
      measured physio-chemical and biotic variables. When expressed as a concentration,
      there was a marked seasonality with concentrations being greater in winter as
      compared in summer; however no spatial trend was evident. When expressed as a
      burden which corrects for differences in tissue mass, there was no seasonality,
      however cadmium oyster burdens increased from south to north. Comparison of
      cadmium accumulation rates oyster(-1) among sites indicated three locations,
      Webster Island, on the west side of Vancouver Island, and two within Desolation
      Sound, Teakerne Arm and Redonda Bay, where point sources of cadmium which are not
      present at all other sampling locations may be contributing to overall oyster
      cadmium burdens. Of the four physio-chemical factors measured only temperature
      and turbidity weakly correlated with tissue cadmium concentrations (r(2)=-0.13;
      p<0.05). By expressing oyster cadmium both as concentration and burden, regional
      and temporal patterns were demonstrated, which may have been missed if just
      concentration was determined.

PMID- 19406439
TI  - Power analysis for biomarkers in mussels for use in coastal pollution monitoring.
AB  - Data from literature on neutral red retention time (NRRT) in lysosomes,
      micronucleus (MN) frequency and condition index (CI) in mussel Mytilus,
      especially Mytilus edulis and Mytilus galloprovincialis, were re-analyzed to
      ascertain their statistical power in detecting a minimum 20% spatial/temporal
      change in field studies. Results showed that CI largely displayed higher
      statistical power (>90%) than lysosomal NRRT and MN frequency (<50%), suggesting
      that data from the latter two biomarkers may lead to erroneous conclusions if
      sample size is inadequate. Samples of green-lipped mussel Perna viridis were also
      analyzed in Hong Kong. To achieve statistically valid power, the optimal sample
      sizes for monitoring lysosomal NRRT, MN frequency, CI and gonosomatic index (GSI)
      were determined as >or=34, >or=90, >or=16 and >or=29, respectively. Natural
      variability of lysosomal NRRT and MN frequency was significantly greater than CI
      and/or GSI in mussels, rejecting the general belief in the greater variability of
      higher-tiered hierarchical biomarkers.

PMID- 19406440
TI  - [POEMS syndrome: a case report].
AB  - POEMS syndrome is a rare multisystemic disorder characterized by polyneuropathy
      (P), organomegaly (O), endocrinopathy (E), blood dyscrasia with M-protein band
      (M), and skin changes (S). The pathogenesis of POEMS syndrome is not completely
      understood. This paraneoplastic syndrome may be associated to bone lesions that
      are characteristically sclerotic or lytic with sclerotic halo and negative at
      bone scintigraphy. We report a case of a 37-year-old man with several
      manifestations of POEMS syndrome who presented bone lesions characteristic of
      osteosclerotic myeloma confirmed by bone biopsy.

PMID- 19406442
TI  - [The usefulness of PET/CT in lung cancer].
AB  - Lung cancer is the leading cause of cancer-related death. Accurate staging is
      essential for the optimal management and treatment of these patients. Positron
      emission tomography (PET) and, more recently, PET/CT have been introduced into
      the diagnostic algorithms for oncologic patients because they provide valuable
      functional information. The hybrid PET/CT technique acquires both anatomic (CT)
      and metabolic (PET) images in a single session, combining the benefits of each
      modality and minimizing their limitations. This article reviews the role of
      PET/CT in lung cancer staging, with emphasis on non-small cell carcinoma,
      evaluating the advantages and limitations of the technique. Other applications of
      the technique, such as planning radiotherapy, are also discussed.

PMID- 19406443
TI  - [Breast MRI--histologic correlation for ductal carcinoma in situ].
AB  - OBJECTIVE: To evaluate the concordance between the breast MRI findings and the
      histologic findings for the size and extension of pure ductal carcinoma in situ
      (DCIS) and to compare this concordance with that of conventional techniques
      (mammography and ultrasonography). MATERIAL AND METHODS: This is a retrospective
      study of consecutive patients diagnosed with DCIS after percutaneous biopsy. We
      estimated Lin's coefficient of concordance for the histologic findings with each
      of the three techniques. We also assessed concordance using Bland-Altman graphs.
      Finally, we determined the impact of the MRI findings on the surgical management
      of patients with DCIS. RESULTS: A total of 32 patients were included in the
      study. Concordance between imaging and histology on tumor size was higher for MRI
      (0.78; 95%CI, 0.62-0.87) than for mammography (0.43; 95%CI, 0.19-0.62) or for
      ultrasonography (0.27; 95%CI, 0.09-0.43). MRI overestimated the size of DCIS by a
      mean of 3 mm, whereas mammography and ultrasonography underestimated it by 9 mm
      and 18 mm, respectively. MRI detected multifocality and multicentricity (7 cases)
      better than mammography (3) or ultrasonography (0). The MRI findings correctly
      changed the surgical management in six patients. CONCLUSION: Breast MRI is better
      than conventional techniques for the evaluation of the size of DCIS. Breast MRI
      also detects more cases of multifocality and multicentricity. We recommend that
      all patients diagnosed with DCIS (especially those with dense breasts) undergo
      breast MRI prior to surgery.

PMID- 19406444
TI  - Long-lasting enhancement of CYP activity after discontinuation of repeated
      administration of phenobarbital in dogs.
AB  - We investigated how long in vivo hepatic cytochrome P450 (CYP) activity is
      enhanced even after discontinuation of repeated oral administration of
      phenobarbital (PB) in dogs using antipyrine clearance, which reflects hepatic CYP
      activity. A single antipyrine (5 mg/kg) was administered intravenously before and
      34 days after the repeated oral administration of PB (5 mg/kg, bid) and 2, 4, 6,
      and 8 weeks after the discontinuation of PB in 5 dogs. Antipyrine clearance was
      increased by the repeated administration of PB, and remained increased 2 and 4,
      but not 6 and 8 weeks after the discontinuation of PB. The result suggests that
      hepatic CYP activity was enhanced by the repeated administration of PB, and this
      enhancement may last for at least 4 weeks even after its discontinuation.

PMID- 19406445
TI  - [Descriptive epidemiology of neuromyelitis optica in the Caribbean basin].
AB  - INTRODUCTION: Data on epidemiology of neuromyelitis optica (NMO) remained scarce
      in the last century, but the recent development of diagnostic criteria now
      enables inclusion of both monophasic and relapsing NMO in epidemiologic studies.
      Given the rarity of NMO, multicentric studies are needed to confirm a presumed
      higher frequency in women and in populations of black/Asian ancestry. The
      Caribbean basin is a suitable area for collecting a large NMO cohort and to
      assess the prevalence, incidence, and mortality of this disorder. PATIENTS AND
      METHODS: This population-based survey of the NMO spectrum in the French West
      Indies (FWI) and Cuba included 151 cases. RESULTS: Ninety-eight patients
      (female/male ratio: 9.8) had NMO. Age of onset in NMO patients was 30.9 years.
      Mean annual incidence of NMO in the French West Indies for the period July 2002
      to June 2007 was 0.20/100,000 inhabitants (IC 95% 0.05-0.35). Incidence rates
      were steady in the FWI during the 1992 to 2007 period. Decreasing mortality in
      the FWI during the 1992 to 2007 period explained the increasing prevalence which
      was 4.20/100,000 inhabitants (IC 95% 3.7-5.7) in June 2007. The prevalence of NMO
      in Cuba on November302004 was 0.52/100,000 inhabitants. (IC 95% 0.39-0.67).
      Prevalence rates did not differ significantly by ethnic group in Cuba, however,
      black Cubans exhibited the highest prevalence. DISCUSSION: Epidemiologic studies
      on NMO in each population are needed to determine whether aggressive therapies
      can reduce the mortality of this devastating disorder. CONCLUSION: In the
      Caribbean basin, NMO involves almost exclusively young women; the epidemiologic
      data confirm its predilection for populations of African ancestry. In the FWI,
      recent and aggressive therapy has lowered mortality but with an increase in the
      prevalence of NMO.

PMID- 19406446
TI  - [Measurement of intra-oral pressure as a contributor for the understanding of
      pneumophonic coordination impairment in Parkinsonian dysarthria].
AB  - INTRODUCTION: Parkinsonian dysarthria can alter oral communication of the
      patients in the long-term. Subthalamic nucleus (STN) stimulation represents an
      interesting therapeutic option, although it does not seem to improve axial signs,
      of which dysarthric speech. The objective of our study was to contribute to the
      evaluation of STN stimulation effects on speech impairment and in particular on
      pneumophonic coordination: this latter parameter can be assessed indirectly by
      evaluating the temporal progression of the intraoral pressure (IOP) during the
      expiratory phase; thus, IOP represents the transient expression of subglottal
      pressure (SGP). PATIENTS AND METHOD: Using a dedicated system (EVA2), 20
      parkinsonian patients were recorded in ON and OFF STN stimulation conditions in
      order to evaluate IOP on three measurement points (2nd, 4th and 6th consonants P)
      during realization of the sentence "Papa ne m'a pas parle de beau-papa" ("Daddy
      did not speak to me about daddy-in-law") which corresponds to a breath group.
      Eleven control subjects were recorded in parallel in order to define reference
      measurements. RESULTS: STN stimulation improved significantly IOP at the level of
      the initial measurement points (2nd P and 4th P), with an effect of convergence
      at the level of the third point (6th P) where the difference between OFF and ON
      STIM conditions was not significant any more. In addition, the performance of the
      patients ON STIM remained much lower than that of the control subjects.
      CONCLUSION: Our results raise the significant concept that IOP measurement can be
      regarded as a relevant indicator for dysarthria in Parkinson's disease. They also
      show that the improvement of pneumophonic coordination by STN stimulation is
      restricted to the initial period of the expiratory phase, confirming again the
      mitigated and controversial effect of STN stimulation on axial signs.

PMID- 19406447
TI  - [Stroke, HIV and meningovascular syphilis: study of three cases].
AB  - INTRODUCTION: Various clinical manifestations can occur in syphilis, especially
      meningovascular syphilis. We report three cases of ischemic stroke related to
      meningovascular syphilis and HIV infection. CASE REPORTS: Three men, aged 30, 31
      and 41, presented typical neurologic deficit leading to the diagnosis of ischemic
      stroke. Radiographic investigations showed internal carotid thrombosis in two
      patients, and a basilar stenosis in the third. CSF analysis and blood samples
      revealed meningovascular syphilis associated with HIV infection. The other
      explorations were normal. CONCLUSION: Due to the reemergence of syphilis, search
      for Treponema pallidum infection should be systematic in young stroke victims.

PMID- 19406448
TI  - Ultrastructural study of archaeological Vitis vinifera L. seeds using rapid
      freeze fixation and substitution.
AB  - The ultrastructure of Vitis vinifera seeds from different archaeological sites
      was studied. Preservation status differed between sites. Preliminary
      investigations of grape seeds from Poggio Bacherina (Chianciano Terme, Siena) and
      Miranduolo (Chiusdino, Siena) showed collapsed or charred tegument, making this
      material suitable for morphometric studies only. Rapid-freeze fixation and
      substitution of grape seeds from Shahr-I Sokhta in Iran and via De' Castellani in
      Florence revealed well preserved tegument suitable for chemical and cytochemical
      analysis. Energy dispersive X-ray microanalysis was used to determine chemical
      composition. Cytochemical analysis based on fluorescent staining with DAPI
      suggested the presence of cytoplasm residues.

PMID- 19406449
TI  - Mass transfer model of nanoparticle-facilitated contaminant transport in
      saturated porous media.
AB  - A one-dimensional model has been evaluated for transport of hydrophobic
      contaminants, such as polycyclic aromatic hydrocarbon (PAH) compounds,
      facilitated by synthetic amphiphilic polyurethane (APU) nanoparticles in porous
      media. APU particles synthesized from poly(ethylene glycol)-modified urethane
      acrylate (PMUA) precursor chains have been shown to enhance the desorption rate
      and mobility of phenanthrene (PHEN) in soil. A reversible process governed by
      attachment and detachment rates was considered to describe the PMUA binding in
      soil in addition to PMUA transport through advection and dispersion. Ultimately,
      an irreversible second-order PMUA attachment rate in which the fractional soil
      saturation capacity with PMUA was a rate control was found to be adequate to
      describe the retention of PMUA particles. A gamma-distributed site model (GS) was
      used to describe the spectrum of physical/chemical constraints for PHEN transfer
      from solid to aqueous phases. Instantaneous equilibrium was assumed for PMUA-PHEN
      interactions. The coupled model for PMUA and PHEN behavior successfully described
      the enhanced elution profile of PHEN by PMUA. Sensitivity analysis was performed
      to analyze the significance of model parameters on model predictions. The
      adjustable parameter alpha in the gamma-distribution shapes the contaminant
      desorption distribution profile as well as elution and breakthrough curves. Model
      simulations show the use of PMUA can be also expected to improve the release rate
      of PHEN in soils with higher organic carbon content. The percentage removal of
      PHEN mass over time is shown to be influenced by the concentration of PMUA added
      and this information can be used to optimize cost and time require to accomplish
      a desired remediation goal.

PMID- 19406450
TI  - Concentrations of persistent organic pollutants in plasma from two species of
      turtle from the Tennessee River Gorge.
AB  - Persistent organic pollutants (POPs) are characterized by their resistance to
      degradation, biomagnification, global transport, and adverse toxicological
      effects. The goal of this study was to determine baseline concentrations of
      several classes of POPs, including polychlorinated biphenyls (PCBs),
      organochlorine pesticides, and polybrominated diphenyl ethers (PBDEs) in two
      turtle species, the Cumberland slider (Trachemys scripta troosti) and the common
      musk turtle (Sternotherus odoratus) from the Tennessee River Gorge. Plasma
      samples from five male and five female adults of each species were analyzed for
      concentrations of 83 PCB congeners, six DDT compounds, four toxaphene congeners,
      18 additional pesticides, pentachlorobenzene, octachlorostyrene, and 28 PBDE
      congeners using gas chromatography/mass spectrometry. In both species, total PCBs
      were the predominant contaminant class, at approximately 10-fold higher
      concentration than p,p'-DDE, total PBDEs, and total chlordanes. Mirex, dieldrin
      and one toxaphene congener (Parlar 50) were also detected at even lower
      concentrations. The female turtles had lower concentrations of some contaminants
      (PCB 153+132, oxychlordane, mirex, PBDE 153, PBDE 154, Sigma PBDEs) than males,
      suggesting maternal transfer to eggs. Cumberland sliders had lower concentrations
      of PCB 138, p,p'-DDE, Sigma DDTs, oxychlordane, PBDE 47, and PBDE 99 than musk
      turtles. The turtles had a unique PBDE pattern with PBDE 100 predominating. The
      POP concentrations were lower than those measured previously in other reptiles
      from contaminated sites where endocrine disruption has been observed. One
      exception was a female musk turtle with 29.9 ng g(-1) p,p'-DDE (wet mass basis),
      which is greater than the concentrations measured in reptiles with evidence of
      endocrine disruption. Additional monitoring and research is necessary to
      determine if other species or age classes in this turtle assemblage might be at
      higher risk of POP accumulation, as well as to assess the potential risk of these
      concentrations on their health and reproduction.

PMID- 19406451
TI  - Autotrophic denitrification in nitrate-induced marine sediment remediation and
      Sulfurimonas denitrificans-like bacteria.
AB  - A group of autotrophic sulfide-oxidizing denitrifying bacteria was identified
      from an aged anthropogenic marine sediment treated by nitrate for the removal of
      recalcitrant organic residues. Based on 16S rDNA similarity, they were most
      closely related to Sulfurimonas denitrificans which oxidizes sulfide to sulfate
      using nitrate as electron acceptor. This group of bacteria was one of the eleven
      operational taxonomy units (OTUs) identified using a universal primer set for
      Eubacteria, but it was accounted for 69% of the total nitrate reduction. Using a
      primer set designed specifically for S. denitrificans, six new S. denitrificans
      like OTUs were identified by cloning-sequencing. They had over 97% similarity
      with S. denitrificans and its relatives, including Thiomicrospira sp. strain CVO,
      Thiomicrospira sp. clone HKT806 and Campylobacterales clone DS169.

PMID- 19406452
TI  - First results on 236U levels in global fallout.
AB  - The global fallout (236)U level in soil was deduced from measurements of (236)U,
      (239+240)Pu and (137)Cs in surface soils which are solely influenced by global
      fallout. A total of 12 soil cores from the depths of 0-10, 0-20 and 0-30 cm were
      collected at a flat forest area in Japan. Concentrations of (239+240)Pu and
      (238)U were determined by alpha-particle spectrometry, while the (236)U/(238)U
      ratio was measured with accelerator mass spectrometry (AMS). Consistent
      (236)U/(239)Pu ratios between 0.212 and 0.253 were found. Using this ratio, the
      total global fallout of (236)U on the earth is estimated to be as much as ca. 900
      kg. This knowledge will contribute to the promotion of research on U isotopes,
      including (236)U, for the fields of geo-resources, waste management and
      geochemistry.

PMID- 19406453
TI  - Occurrence and potential risks of harmful algal blooms in the East China Sea.
AB  - Harmful algal blooms (HABs) have drawn great attention in coastal areas worldwide
      in the past decades because of their multiple effects on marine ecosystems as
      well as public health. This study utilized geographic information system (GIS)
      techniques to analyze the primary data on HABs, as well as shellfish toxins data,
      in the East China Sea from 2000 to 2006. The frequency of HABs was mapped by
      kernel density estimation, and the relative risk posed by HABs was assessed based
      on their physical-chemical characteristics. In addition, the spatial patterns and
      the trend of HAB events were examined by nearest neighbor analysis and time
      series analysis, respectively. The results revealed that HAB events not only had
      an increasing trend and significant seasonality, but also were clustered in space
      and time. HAB events displayed a higher frequency and a higher risk in Zhejiang
      coastal waters, particularly in the Zhoushan Archipelago, the largest marine
      fishery in China. Shellfish toxins were detected in areas with high HAB risk, but
      were not correlated with the risk. This paper provides a novel method to assess
      the relative risk caused by HABs and some useful information for HAB monitoring
      and management and aquaculture development.

PMID- 19406454
TI  - The use of muscle burden in rabbitfish Siganus oramin for monitoring polycyclic
      aromatic hydrocarbons and polychlorinated biphenyls in Victoria Harbour, Hong
      Kong and potential human health risk.
AB  - Muscle concentrations of polycyclic aromatic hydrocarbons (PAHs) and
      polychlorinated biphenyls (PCBs) were determined in rabbitfish Siganus oramin
      collected from Victoria Harbour and its vicinity, Hong Kong from 2004 to 2007.
      Spatially, relatively higher levels of [summation operator]PAH (1.05-4.26 microg
      g(-1)) and [summation operator]PCB (45.1-76.9 ng g(-1)) were determined in the
      central and western sites inside the harbour. Temporally, upward trend of
      [summation operator]PAH, accompanied with a proportion shift from high molecular
      weight to low molecular weight PAHs, was detected during the three-year study
      period, suggesting a heavier marine traffic in Victoria Harbour and its western
      region. However, human health risk assessment based on five individual PAHs
      indicated that PAHs in fish muscles posed minimal health risk through
      consumption. In contrast, a downward trend of [summation operator]PCB was
      registered as the open use of PCBs has been banned. Despite this, the level of
      [summation operator]PCB in fish muscles still posed a health risk on the local
      people who have a high fish consumption rate. While seasonal influences on
      [summation operator]PAH/[summation operator]PCB accumulation in S. oramin seemed
      to be negligible, our findings in S. oramin were in line with the established PAH
      and PCB levels in sediments and/or mussels from the harbour, suggesting S. oramin
      can be used as a model fish species for monitoring PAHs and PCBs in the region.

PMID- 19406455
TI  - Use of numerical models for determination of best sampling locations for
      monitoring of large lakes.
AB  - The implementation of the European Union Water Framework Directive (WFD) that
      requires all surface waters to achieve at least good status by year 2015 presents
      a challenge to local authorities responsible for the monitoring programmes.
      Obtaining a single representative value for each water quality parameter may be
      extremely difficult to achieve in the case of large lakes, which may be
      characterised by significant spatial and temporal variation of water quality
      parameters. The aim of this paper is to present a methodology, which can support
      the decision making as to the best locations for water quality sampling when
      developing monitoring systems of large lakes. The methodology is based on three
      dimensional hydrodynamic and a conservative tracer transport numerical modelling
      and utilises the concept of flushing and residence time. The 3D numerical model
      of Lough Corrib located in the west of Ireland was created and used to calculate
      its residence time and flushing pathways. Based on the results it was possible to
      identify the areas in the lake that are characterised by the local residence time
      values close to the lake's average as well as by the values significantly lower
      and higher. Three water classes have been introduced and the authors recommend
      that sampling takes place in all three classes at various frequencies. Spatial
      distribution of the flushing pathways allows identifying the areas in the lake
      that best represent the lake's average conditions both in the long term and
      seasonally, where monitoring can be carried out at the required frequency; worst
      affected areas can also be identified. The methodology can be used to improve
      robustness of the monitoring programme and may also contribute towards the
      reduction of both sampling and analytical costs, both at the design and
      operational stages.

PMID- 19406456
TI  - Urologic diagnoses among infants hospitalized for urinary tract infection.
AB  - OBJECTIVES: To determine the prevalence of urologic disease among infants
      hospitalized for urinary tract infections (UTIs) at our institution. The
      prevalence of urologic anomalies among infants (<400 days old) hospitalized for
      UTIs has not been previously reported. METHODS: We retrospectively examined the
      records of all infants hospitalized for UTI at our institution, a free-standing
      children's hospital in the United States, for a 10-year period. Race, sex, and
      subsequent urologic diagnosis (using codes from the 9(th) edition of the
      International Classification of Diseases [ICD-9] were tabulated. Individual
      charts were reviewed to confirm documentation and workup of UTI. RESULTS: We
      identified 914 infants hospitalized at our institution from January 1996 to
      December 2007, with an ICD-9-coded diagnosis of UTI. Of these 914 infants, 258
      were subsequently given a urologic diagnosis. However, only 130 of these patients
      had well-documented UTI (14.2% of 914 children). Of this cohort, 55.4% were boys.
      The most common diagnoses were hydronephrosis (37.7%), vesicoureteral reflux
      (69.2%), and obstructive uropathy (23.1%). CONCLUSIONS: Our data have indicated
      that > or =14% of all infants hospitalized for UTI have urologic anomalies.
      Vesicoureteral reflux, obstructive uropathy, and hydronephrosis are common
      diagnoses. We therefore conclude that infants admitted with a diagnosis of UTI
      should undergo screening for anatomic abnormalities.

PMID- 19406457
TI  - Does benign prostatic tissue contribute to measurable PSA levels after radical
      prostatectomy?
AB  - OBJECTIVES: To provide insights into the likelihood that benign prostatic tissue
      represents a source of measurable prostate-specific antigen (PSA) after radical
      prostatectomy. METHODS: From October 2000 to December 2006, 1308 consecutive men
      underwent open radical retropubic prostatectomy by a single surgeon. Of these
      1308 men, 331 (25.3%) met our criteria for having "extremely" low-risk disease as
      determined by the preoperative and pathologic factors, including a preoperative
      PSA level <10 ng/mL, clinical Stage T1c or T2a, a Gleason score of < or =6, an
      estimated cancer volume in the specimen of <5%, and no evidence of positive
      surgical margins. This cohort was selected because any measurable PSA level would
      be highly suspicious for a benign origin. Undetectable PSA was defined as a PSA
      level of < or =0.04 ng/mL. A measurable PSA level included values between 0.05
      and 0.14 ng/mL on > or =2 consecutive measurements 6 months apart. Biochemical
      recurrence was defined as 3 consecutively increasing PSA levels with a peak level
      of > or =0.15 ng/mL. RESULTS: At 3 months to 6 years of follow-up (mean 36.2
      months), 0.6% and 0.3% of patients had developed a measurable PSA level or
      biochemical recurrence, respectively. The single patient with biochemical
      recurrence responded to salvage radiotherapy, strongly suggesting a malignant
      etiology for the recurrence. CONCLUSIONS: A measurable PSA level or biochemical
      recurrence was an extraordinarily rare event in our select group of patients with
      extremely low-risk disease. These results provide compelling evidence that
      retained benign prostatic elements are an unlikely source of elevated PSA levels
      in men who have undergone radical prostatectomy.

PMID- 19406458
TI  - Analysis of techniques to secure the renal hilum during laparoscopic donor
      nephrectomy: review of the FDA database.
AB  - OBJECTIVES: To characterize the mechanisms of failure and patient outcomes during
      complications with the use of endoscopic stapling devices, nonlocking titanium
      clips, and locking polymer clips during laparoscopic donor nephrectomy. METHODS:
      The Food and Drug Administration's medical device complication database,
      Manufacturer and User Facility Device Experience database (MAUDE), was evaluated
      for pure and hand-assisted laparoscopic donor nephrectomies from 1992 to 2007
      with the broadest keywords possible. In an attempt to estimate the failure rates
      by device type, a "denominator of use" was calculated using Organ Procurement and
      Transplant Network data multiplied by previously published survey-determined
      usage rates. RESULTS: In the 92 complications identified, 59 (64%), 21 (23%), and
      12 (13%) failures of endoscopic staplers, titanium clips, and locking clips had
      occurred, respectively. The most common mechanisms of stapler failure were
      missing/malformed staple lines (51%) and failure to release (25%). The most
      common titanium clip failures resulted from scissoring or malformation (52%),
      jamming (19%), and dislodgement (14%). Clip dislodgement was most common with the
      locking clip, either postoperatively in 7 (58%) or intraoperatively in 3 (25%).
      Intraoperative conversions were required for 21 (36%), 1 (5%), and 2 (17%) for
      staplers, titanium clips, and locking clips, respectively. The estimated overall
      failure rate was 3.0% for staplers, 4.9% for titanium clips, and 1.7% for locking
      clips. CONCLUSIONS: The anticipation of potential device-specific failures during
      laparoscopic donor nephrectomy, coupled with knowledge of how to handle failure
      when it does occur, could improve procedure safety.

PMID- 19406460
TI  - Endometrial cancer and obesity: epidemiology, biomarkers, prevention and
      survivorship.
AB  - Endometrial cancer is the most common gynecologic malignancy in the Western world
      and is strongly associated with obesity. Despite the fact that most cases are
      diagnosed in early, more favorable stages, endometrial cancer incidence and
      mortality rates are on the rise. Morbidly obese women with endometrial cancer are
      more likely to die of their co-morbidities and also of their cancers when
      compared to their leaner cohorts. Given the increasing rates of morbid obesity in
      the United States, it is essential to develop appropriate screening tools and
      guidelines to reduce cancer morbidity and death amongst this group. Through an
      analysis of the existing literature, we present a review of the epidemiologic
      trends in obesity and endometrial cancer, discuss the promising role of screening
      biomarker studies, review prevention efforts and modifiable risk factors, and
      ways in which health outcomes and quality of life for endometrial cancer
      survivors may be optimized.

PMID- 19406459
TI  - Adjuvant carboplatin and paclitaxel chemotherapy interposed with involved field
      radiation for advanced endometrial cancer.
AB  - OBJECTIVE: To evaluate recurrence and survival associated with adjuvant
      carboplatin and paclitaxel chemotherapy interposed with involved field radiation
      for advanced endometrial cancer. METHOD: This is a prospective cohort study of
      women with Stage III and IV endometrial cancer treated at a single institution
      between April 2002 and July 2006. Adjuvant therapy consisted of 4 cycles of
      intravenous paclitaxel (175 mg/m(2)) and carboplatin (350 mg/m(2)) every 3 weeks,
      followed by external beam radiotherapy (RT) to the pelvis (45 Gy), then another 2
      cycles of chemotherapy. Para-aortic RT and/or HDR vault brachytherapy were added
      at the discretion of the treating physician. Toxicity of this protocol was
      previously reported. Primary endpoints for this study were disease-free and
      overall survival rates. RESULTS: Forty-three patients with a median age of 64
      years (46-83 years) were evaluated. The majority had Stage IIIC disease (63%),
      and the most common histology was serous carcinoma (49%). Six cycles of
      combination chemotherapy were completed in 81%, and all patients completed pelvic
      RT. Median follow-up was 30 months (9-71 months). Twenty-one patients (49%)
      recurred at a median of 17 months (7-62 months). There were only 3 local
      recurrences, including 2 in the pelvis and 1 in the vagina/vulva. Median disease
      free survival (DFS) was 50 months and median overall survival (OS) has not been
      reached. Three year DFS and OS rates were 53% and 68%, respectively. CONCLUSION:
      Adjuvant carboplatin and paclitaxel chemotherapy interposed with involved field
      radiation is associated with a low rate of local recurrence and favorable
      survival for advanced endometrial cancer.

PMID- 19406462
TI  - Factors affecting chilled storage of zebrafish (Danio rerio) embryos.
AB  - Chilled storage of zebrafish embryos was investigated at a temperature that
      arrests embryonic development as this technique might offer interesting practical
      applications. Five parameters played an important role for chilled storage: (a)
      storage temperature, (b) development stage of embryos, (c) storage solution
      (extender), (d) postchilling treatment, and (e) inhibition of growth of
      microorganisms by antibiotics. The optimal chilling temperature was 8 degrees C.
      Prim-5 stage (24h postfertilization [hpf]) and prim-25 stage (36 hpf) embryos had
      similar high chilling resistance and could be chilled for 33h without a loss in
      viability. Five-somite stage (12 hpf) embryos had a lower chilling resistance and
      could be chilled only for 14h without a loss in viability. After longer
      incubation periods, the viability started to decrease. Under these conditions,
      chilling in physiologic saline solutions was superior to that in water. Fifty
      percent of the prim-5 stage and prim-25 stage embryos survived for 41h at 8
      degrees C in water but for 46h in physiologic saline solution. A similar effect
      was observed for 5-somite stage embryos (50% survival rate in water, 28h; 50%
      survival rate in physiologic saline solution, 35h). When embryos were incubated
      in physiologic saline solution instead of water in the postchilling phase, the
      embryo viability was positively affected, too. Also, supplementation of the
      storage solution with antibiotics (penicillin and streptomycin) increased the
      viability of chilled embryos. In summary, the current study shows that chilled
      storage of zebrafish embryos is possible for sufficiently long periods to
      synchronize the development of embryos deriving from different spawning dates or
      to delay the development for experimental purposes. To prolong the storage
      periods, further development and standardization of the methodology is necessary.

PMID- 19406461
TI  - Case report: Recurrence of a uterine tumor resembling ovarian sex-cord tumor.
AB  - BACKGROUND: Uterine tumors resembling ovarian sex-cord tumors are very rare
      uterine neoplasias that generally behave in a benign manner. We report the case
      of a uterine tumor resembling an ovarian sex-cord tumor that recurred after
      hysterectomy. CASE: A 35-year-old nulliparous woman presented with abdominal
      discomfort, galactorrhea and abnormal vaginal bleeding. Ultrasound examination
      showed a heterogeneous uterine tumor composed of cystic and solid parts. Because
      of the patient's desire to preserve fertility, tumor resection was scheduled.
      Frozen sections suggested malignancy and led to abdominal hysterectomy. The final
      histological diagnosis was uterine tumor resembling ovarian sex-cord tumor. Three
      years into follow-up, metastasis occurred. CONCLUSION: Although uterine tumors
      resembling ovarian sex-cord tumors generally behave in a benign manner, they may
      in rare cases metastasize.

PMID- 19406463
TI  - Leisure activities and adolescent psychological well-being.
AB  - We examined the validity of the reported link between well-being and leisure
      participation in adolescents. Nine hundred and forty-seven, Year 10 students from
      19 schools in Adelaide, South Australia, were recruited. Participants completed a
      questionnaire concerning participation in social, non-social and unstructured
      leisure activities as well as measures of personality. As expected, personality
      variables were better predictors of adolescent well-being than spare-time use,
      although engagement in less structured leisure activities was associated with
      poorer psychological well-being and substance use. These findings support
      previous personality research which suggests that spare-time use may be related
      to well-being only insofar as individuals who are psychologically healthy tend to
      be involved in structured leisure activities. The implications of these findings
      for school policy and future research concerning the links between leisure
      involvement and psychological well-being are discussed.

PMID- 19406464
TI  - New insights into the compulsion to use tobacco from an adolescent case-series.
AB  - Nicotine addiction is the most common preventable cause of premature death
      presenting during adolescence. No prior study has described the onset of this
      condition based on case histories. We used trained personnel to conduct
      individual semi-structured interviews to obtain case histories from 50 adolescent
      and young adult current and former smokers. Smokers experience a compulsion to
      use tobacco that spans a spectrum of severity from wanting, to craving, to
      needing. The compulsion is commonly experienced as originating foreign to the
      will of the smoker and recurs with a predictable periodicity that determines the
      latency from smoking one cigarette to wanting, craving or needing another. Novice
      smokers could experience latencies as lengthy as a few weeks, and more
      experienced smokers attributed their escalation in smoking frequency to the
      shortening of their latencies. Wanting, craving or needing tobacco, as described
      in this study, are pathognomonic for a compulsion to use tobacco.

PMID- 19406465
TI  - The effect of ultra-nanocrystalline diamond films on the proliferation and
      differentiation of neural stem cells.
AB  - The interaction of ultra-nanocrystalline diamond (UNCD) with neural stem cells
      (NSCs) has been studied along with its surface modification in order to improve
      its function as a biomaterial. Hydrogen- and oxygen-terminated UNCD films were
      compared with standard grade polystyrene in terms of their impact on the growth,
      expansion and differentiation of NSCs. When NSCs were cultured on these
      substrates in low serum and without any differentiating factors, hydrogen
      terminated UNCD films spontaneously induced cell proliferation and neuronal
      differentiation. Oxygen-terminated UNCD films were also shown to further improve
      neural differentiation, with a preference to differentiate into oligodendrocytes.
      Hence, controlling the surface properties of UNCD could manipulate the
      differentiation of NSCs for different biomedical applications. These observations
      raise the potential for the use of UNCD as a biomaterial for central nervous
      system transplantation and tissue engineering.

PMID- 19406467
TI  - A poly(D,L-lactide) resin for the preparation of tissue engineering scaffolds by
      stereolithography.
AB  - Porous polylactide constructs were prepared by stereolithography, for the first
      time without the use of reactive diluents. Star-shaped poly(D,L-lactide)
      oligomers with 2, 3 and 6 arms were synthesised, end-functionalised with
      methacryloyl chloride and photo-crosslinked in the presence of ethyl lactate as a
      non-reactive diluent. The molecular weights of the arms of the macromers were
      0.2, 0.6, 1.1 and 5 kg/mol, allowing variation of the crosslink density of the
      resulting networks. Networks prepared from macromers of which the molecular
      weight per arm was 0.6 kg/mol or higher had good mechanical properties, similar
      to linear high-molecular weight poly(D,L-lactide). A resin based on a 2-armed
      poly(D,L-lactide) macromer with a molecular weight of 0.6 kg/mol per arm (75
      wt%), ethyl lactate (19 wt%), photo-initiator (6 wt%), inhibitor and dye was
      prepared. Using this resin, films and computer-designed porous constructs were
      accurately fabricated by stereolithography. Pre-osteoblasts showed good adherence
      to these photo-crosslinked networks. The proliferation rate on these materials
      was comparable to that on high-molecular weight poly(D,L-lactide) and tissue
      culture polystyrene.

PMID- 19406468
TI  - Intermediate conductance Ca2+-activated potassium channel (KCa3.1) in the inner
      mitochondrial membrane of human colon cancer cells.
AB  - Patch-clamping mitoplasts isolated from human colon carcinoma 116 cells has
      allowed the identification and characterization of the intermediate conductance
      Ca(2+)-activated K(+)-selective channel K(Ca)3.1, previously studied only in the
      plasma membrane of various cell types. Its identity has been established by its
      biophysical and pharmacological properties. Its localisation in the inner
      membrane of mitochondria is indicated by Western blots of subcellular fractions,
      by recording of its activity in mitochondria made fluorescent by a mitochondria
      targeted fluorescent protein and by the co-presence of channels considered to be
      markers of the inner membrane. Moderate increases of mitochondrial matrix
      [Ca(2+)] will cause mtK(Ca)3.1 opening, thus linking inner membrane K(+)
      permeability and transmembrane potential to Ca(2+) signalling.

PMID- 19406466
TI  - Mixed micelle systems formed from critical micelle concentration and temperature
      sensitive diblock copolymers for doxorubicin delivery.
AB  - Mixed micelles formed by critical micelle concentration (Cmc) character's diblock
      copolymer, and temperature-sensitive character's diblock copolymer were studied
      for their capabilities in improving stability with and without drug. Experimental
      results showed that this type of mixed micellar systems possessed complementary
      effects in adjusting external temperature shift (storage vs. body temperature)
      and concentration change (dilution after intravenous injection). Therefore, they
      provided excellent stability as drug carriers. Further results obtained from
      physicochemical property and drug release kinetics studies demonstrated such
      systems could also be applied to physiological conditions, in compliance with
      varied pH environments. We concluded that the newly developed mixed micelles can
      serve as a potential injectable drug delivery system for anticancer drugs, such
      as doxorubicin and many others.

PMID- 19406469
TI  - Lipids in Ca2+ signalling--an introduction.
AB  - Lipids and lipid-derived metabolites are increasingly recognised as bonafide
      signalling molecules that regulate many cellular processes. These include the
      well-established InsP(3), diacylglycerol (DAG), PIP(2), PIP(3) and arachidonic
      acid (AA), as well as other poly-unsaturated fatty acids (PUFAs),
      lysophospholipids, sphingolipids, endocannabinoids and endovanilloids. They
      regulate a plethora of molecules that are involved in Ca(2+) signalling,
      including various ion channels, pumps and transporters, thereby triggering,
      modulating and fine-tuning Ca(2+) signals. Although appreciated individually, it
      seems timely to highlight the overall impact of lipids as signalling molecules
      and their role in Ca(2+) signalling, and this is the aim of this special issue of
      Cell Calcium.

PMID- 19406470
TI  - Comparative analysis of IL6 promoter and receptor polymorphisms in myelodysplasia
      and multiple myeloma.
AB  - The serum levels of interleukin 6 (IL6) are known to be elevated in two diseases
      of the elderly age, myelodysplastic syndrome (MDS) and multiple myeloma (MM).
      Authors suppose that one of the possible causes of this elevation could be a
      difference between these patients and healthy subjects in the frequency of
      polymorphic variants of the genes regulating IL6 levels. Scarce and contradictory
      comparative data are available for MM and to our best knowledge this is the first
      study on IL6 promoter and IL6 receptor (IL6R) polymorphism in MDS. Therefore we
      determined the Asp358Ala polymorphism of the IL6 receptor gene and the -174 G>C
      promoter polymorphism of the IL6 gene in blood samples of 102 MDS and 100 MM
      patients and 99 age- and sex-matched hospitalized controls had been tested for
      this purpose as well. There was no significant difference between patients with
      either disease and controls regarding IL6 promoter/L-6R. Authors therefore assume
      other mechanisms causing high IL6 levels are not related to either of these
      polymorphisms. Moreover authors consider important to propose a hypothesis how
      elements of signal transduction in iron metabolism might be involved in the
      development of MM and MDS in elderly age.

PMID- 19406472
TI  - Bispecific immunotoxins.

PMID- 19406471
TI  - Successful Nilotinib therapy in an imatinib-resistant chronic myeloid leukemia
      patient displaying an intron-derived insertion/truncation mutation in the BCR-ABL
      kinase domain.

PMID- 19406473
TI  - Gain of the short arm of chromosome 2 (2p) is a frequent recurring chromosome
      aberration in untreated chronic lymphocytic leukemia (CLL) at advanced stages.
AB  - Using array-based CGH, we identified 2p gain in 22/78 (28%) untreated Binet
      stages B/C CLL, which was the second most frequent copy number change after 13q
      deletion. It never occurred as a sole abnormality and was associated with other
      changes (6q deletion; 1p gain). The region of 2p gain frequently included two
      oncogenes, REL and MYCN. All patients with gain of REL were unmutated for IGHV
      (p=0.03). Gain of MYCN was associated with increased mRNA expression (p=0.005),
      suggesting a pathogenic role for MYCN. Gain of 2p appears to be a marker of
      progression and may contribute to the poor prognosis.

PMID- 19406474
TI  - Total serum tryptase: a predictive marker for KIT mutation in acute myeloid
      leukemia.
AB  - Human tryptase is a serine protease expressed in mast-cells. We previously
      observed that AML blast cells, cultured in vitro from a KIT D816Y patient, give
      rise to adherent cells with mast-cell like phenotype and tryptase was released in
      the serum-free medium. To correlate total serum tryptase (ts-try) levels with
      cytogenetic features and KIT mutational status, we analyzed serum samples from
      AML patients at diagnosis. In 70 out of 155 patients (45%) we detected elevated
      ts-try (>15 ng/mL), significantly linked to t(8;21) (P < .001) and inv(16) (P =
      .007). In patients that achieved complete remission the ts-try decreased to
      normal values. In 75 patients screened for KIT mutation, we found a clear
      relationship between elevated ts-try and mutated patients with t(8;21) (P <
      .001). In conclusion, we propose that checking for ts-try at diagnosis of AML may
      be a simple tool to select patients to be addressed to KIT mutation screening.

PMID- 19406475
TI  - The mechanism of HTLV-1 LTR activation by TPA varies in different human T-cell
      lines: role of specific PKC isoforms.
AB  - We demonstrate here that TPA activates HTLV-1 LTR expression in Jurkat and H9 T
      cell lines, by strictly different mechanisms. In Jurkat cells this activation is
      exerted by a PKCalpha- and PKCvarepsilon-antagonized mechanism which operates
      through an Sp1 binding site residing within the Est responsive region 1 of the
      LTR. On the other hand, in H9 cells TPA activates the LTR by two consecutive
      mechanisms; the first depends on PKCeta activity and is exerted through the 21 bp
      repeats of the LTR, whereas the second is analogous to that observed in Jurkat
      cells, except that it is antagonized by PKCdelta.

PMID- 19406476
TI  - Immune effects of HFO on European sea bass, Dicentrarchus labrax, and Pacific
      oyster, Crassostrea gigas.
AB  - The European sea bass, Dicentrarchus labrax, and the Pacific oyster, Crassostrea
      gigas, were exposed to a soluble fraction of heavy fuel oil for 5 and 9 days,
      respectively. The organisms were then transferred to non-contaminated seawater
      for 1 month. The bioaccumulation and elimination of PAHs in contaminated tissues
      were dissimilar between species. In fish, acenaphthene and naphthalene were
      detected and naphthalene was still detectable 30 days after the beginning of the
      recovery period. In oysters, on the other hand, pyrene and phenanthrene were
      bioaccumulated and 14 days after exposure no more PAHs were detected. Concerning
      innate immune parameters, the increase of haemolytic activity of the alternative
      complement pathway in fish and the reduction of phenoloxidase activity in oysters
      endured, respectively, 1 and 2 weeks in contaminated organisms. This indicates
      that these two enzymatic cascades could be quite useful for monitoring pollution
      by oil.

PMID- 19406477
TI  - Mutagenic properties of PM2.5 urban pollution in the northern Italy: the nitro
      compounds contribution.
AB  - PM2.5 is the breathable fraction of the particulate matter and some adverse
      health effects, such as respiratory functionality, cardiological diseases and
      cancer, can be in some measure attributable to this risk factor exposure. Some of
      the most carcinogen compounds transported by PM2.5 are nitro-compounds. In this
      study, a strengthened in vitro bioassay--able to predict the
      mutagenic/carcinogenic activity of the environmental mixtures--was conducted on
      PM2.5 organic extracts to define the nitro-compounds burden. PM2.5 air pollution
      was daily monitored, during 2006, in three cities located in the Northern part of
      Italy (Torino, Pavia and Verona) and the mutagenic properties of the PM2.5
      organic extracts were assessed with the Ames test. The bacterial used in this
      study were three Salmonella typhimurium strains: TA98, nitroreductase-less mutant
      TA98NR and YG1021 carrying a nitroreductase-producing plasmid. The annual PM2.5
      mean level measured in Torino was 46.5 (+/-31.6) microg/m(3), in Pavia 34.8 (+/
      25.1) microg/m(3), and in Verona 37.3 (+/-27.8) microg/m(3), while the
      mutagenicity expressed as TA98 net reverants/m(3) was 28.0 (+/-22.1), 28.3 (+/
      24.9), and 34.2 (+/-30.9) respectively. Monthly pool bioassays, conducted with
      the three different strains, showed a greater mutagenic response of the YG1021 in
      each city. The relationship among the mutagenic answers for YG1021:TA98:TA98NR
      was about 6:3:1 (p<0.001). Over nitroreductase activity enhanced the response of
      2.2, 2.0 and 1.7 times for Torino, Pavia, and Verona (ANOVA Torino p<0.05)
      respectively. Without nitroreductase activity the genotoxicity was limited. These
      biological findings are able to describe a relevant role played by the nitro
      compounds in the mutagenic properties of the urban PM2.5 in the Padana plain;
      moreover the bacterial nitroreductase plays a predominant role in DNA interaction
      primarily for Torino PM2.5 extracts.

PMID- 19406479
TI  - MUC1 in human milk blocks transmission of human immunodeficiency virus from
      dendritic cells to T cells.
AB  - Mother-to-child transmission of human immunodeficiency virus-1 (HIV-1) occurs
      frequently via breast-feeding. HIV-1 targets DC-SIGN+ dendritic cells (DCs) in
      mucosal areas that allow efficient transmission of the virus to T cells. Here, we
      demonstrate that the epithelial mucin MUC1, abundant in milk, efficiently bound
      to DC-SIGN on DC. The O-linked glycans within the mucin domain contained Lewis X
      structures, that were specifically recognized by the receptor. Interestingly,
      MUC1 prevented DC-SIGN-mediated transmission of HIV-1 from DCs to CD4+ T cells.
      We hypothesize that repetitive units of Lewis X, within the mucin domain, play an
      important role in inhibiting transmission of HIV-1 from mother to child.

PMID- 19406478
TI  - The first transmembrane region of the beta-chain stabilizes the tetrameric Fc
      epsilon RI complex.
AB  - The family of activating immune receptors stabilizes via the 3-helix assembly
      principle. A charged basic transmembrane residue interacts with two charged
      acidic transmembrane residues and forms a 3-helix interface to stabilize receptor
      complexes in the lipid bilayer. One family member, the high affinity receptor for
      IgE, Fc epsilon RI, is a key regulator of immediate allergic responses.
      Tetrameric Fc epsilon RI consists of the IgE-binding alpha-chain, the
      multimembrane-spanning beta-chain and a dimer of the gamma-subunit (Fc epsilon R
      gamma). Comparative analysis of these seven transmembrane regions indicates that
      Fc epsilon RI does not meet the charge requirements for the 3-helix assembly
      mechanism. We performed alanine mutagenesis to show that the only basic amino
      acid in the transmembrane regions, beta K97, is not involved in Fc epsilon RI
      stabilization or surface upregulation, a hallmark function of the beta-chain.
      Even a beta K97E mutant is functional despite four negatively charged acidic
      amino acids in the transmembrane regions. Using truncation mutants, we
      demonstrate that the first uncharged transmembrane domain of the beta-chain
      contains the interface for receptor stabilization. In vitro translation
      experiments depict the first transmembrane region as the internal signal peptide
      of the beta-chain. We also show that this beta-chain domain can function as a
      cleavable signal peptide when used as a leader peptide for a Type I protein. Our
      results provide evidence that tetrameric Fc epsilon RI does not assemble
      according to the 3-helix assembly principle. We conclude that receptors formed
      with multispanning proteins use different mechanisms of shielding transmembrane
      charged amino acids.

PMID- 19406480
TI  - Isoform identification and characterization of Art v 3, the lipid-transfer
      protein of mugwort pollen.
AB  - Art v 3, the lipid-transfer protein (LTP) of Artemisia vulgaris pollen is a
      relevant allergen showing frequent cross-reactivity with homologues in other
      plants. Here we report the identification of four full-length Art v 3 sequences
      obtained by cDNA cloning using mass spectrometry-based sequencing. Two isoforms,
      Art v 3.0201 and Art v 3.0301 were expressed as soluble proteins in Escherichia
      coli Rosetta-gami B(DE3) pLysS using different expression systems. Purified
      natural and recombinant Art v 3 demonstrated similar secondary structures in
      circular dichroism analysis. All preparations showed high thermal stability but
      low resistance to gastric digestion with pepsin. Patient-specific IgE reactivity
      patterns to natural or recombinant isoallergens were observed among Art v 3
      sensitized subjects. Using Immuno Solid-phase Allergen Chip (ISAC) assays,
      frequent cross-reactivity of Art v 3 with LTPs from peach and hazelnut was shown.
      The biological activity of both isoforms was comparable to the natural allergen
      in basophil release assays. The newly identified sequences provide the basis for
      recombinant mugwort LTP production enabling batch-to-batch reproducibility and
      thus ensuring high-quality products for diagnosis and therapy.

PMID- 19406481
TI  - Fetal membranes exhibit selective leukocyte chemotaxic activity during human
      labor.
AB  - One of the characteristics of the labor process in women is leukocyte recruitment
      into reproductive tissues. These migrating cells may play a role in the induction
      of functional and biochemical changes associated with the rupture of fetal
      membranes during labor. This study was undertaken to assess whether human fetal
      membranes induce leukocyte chemotaxis during labor as well as to identify and
      characterize leukocyte chemoattractants secreted by these tissues. Leukocyte
      chemotactic activity of fetal membrane extracts obtained from women with full
      term pregnancies and spontaneous active labor was compared with extracts from
      women without labor. The number and phenotype of attracted leukocytes were
      analyzed by flow cytometry. Chemokines were quantified using a Multiplex system
      and were identified by immunofluorescence histochemistry. Although all tested
      extracts induced chemotaxis of leukocytes, those prepared from women undergoing
      labor induced higher responses. Polymorphonuclear leukocyte chemotaxis increased
      approximately three-fold in response to extract from fetal membranes with labor.
      The same extracts elicited a significant increase in attracted monocytes (36
      fold) as well as T and B lymphocytes, and NK cells (all five-fold) when compared
      to extracts from women without labor. This enhanced chemotactic activity was
      associated with the presence of IL-8, MCP-1, IP-10 and MIP-1alpha. We conclude
      that fetal membrane extracts obtained from women during labor exhibit selective
      chemotaxis for specific leukocyte subpopulations in vitro. This process may
      contribute to a microenvironment composed of specific leukocytes that promotes
      and amplifies biochemical changes in the fetal membranes during labor.

PMID- 19406482
TI  - Functional expression of pattern recognition receptors in tissues of the human
      female reproductive tract.
AB  - The human female reproductive tract (FRT) must balance the requirements of
      procreation with the demands of protection from pathogen invasion. We hypothesize
      that the FRT expresses functional pattern recognition receptors (PRRs), including
      Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)
      proteins that may mediate these tasks. Expression of PRRs was evaluated in FRT
      tissues by RT-PCR. PRR function within FRT tissue cells was determined by CXCL8
      (IL-8) production in response to treatment with PRR agonists. We now report that
      TLRs7-9 are expressed in Fallopian tube, uterine endometrium, cervix and
      ectocervix, while TLR10 expression is restricted to Fallopian tube. NOD1 and NOD2
      and the signal transducer RICK were detected in all FRT tissues. Stimulation of
      FRT tissue cells with PRR ligands resulted in secretion of CXCL8. Results of
      these studies indicate that PRRs are functionally expressed in FRT tissues, and
      suggest that these receptors mediate microbial recognition and immune defense in
      the reproductive tract.

PMID- 19406484
TI  - Noise levels in neonatal intensive care unit and use of sound absorbing panel in
      the isolette.
AB  - OBJECTIVE: The purposes of this study were to measure the noise level of a busy
      neonatal intensive care unit (NICU) and to determine the effect of sound
      absorbing panel (SAP) on the level of noise inside the isolette. METHODS: The
      sound pressure levels (SPL) of background noise, baby crying, alarms and closing
      of isolette's door/portholes were measured by a 2235-Bruel&Kjaer Sound Level
      Meter. Readings were repeated after applying SAP (3D pyramidal shaped open cell
      polyurethane foam) to the three lateral walls and ceiling of the isolette.
      RESULTS: The median SPL of background noise inside the NICU was 56dBA and it
      decreased to 47dBA inside the isolette. The median SPL of monitor alarms and baby
      crying inside the isolette were not different than SPL measured under radiant
      warmer (p>0.05). With SAP, the median SPL of temperature alarm inside the
      isolette decreased significantly from 82 to 72dBA, monitor alarm from 64 to
      56dBA, porthole closing from 81 to 74dBA, and isolette door closing from 80 to
      68dBA (p<0.01). There was a significant reduction in the noise produced by baby
      crying when SAP was used in the isolette (79dBA vs 69dBA, respectively)
      (p<0.0001). There was also significant attenuation effect of panel on the
      environmental noise. CONCLUSIONS: The noise level in our NICU is significantly
      above the universally recommended levels. Being inside the isolette protects
      infants from noise sources produced outside the isolette. However, very high
      noises are produced inside the isolette as well. Sound absorbing panel can be a
      simple solution and it attenuated the noise levels inside the isolette.

PMID- 19406483
TI  - Bovine herpesvirus type 1 infection of bovine bronchial epithelial cells
      increases neutrophil adhesion and activation.
AB  - Respiratory infection of cattle with bovine herpesvirus type 1 (BHV-1)
      predisposes cattle to secondary pneumonia with Mannheimia haemolytica as part of
      the bovine respiratory disease complex (BRD). One cell type that has received
      limited investigation for its role in the inflammation that accompanies BRD is
      the respiratory epithelial cell. In the present study we investigated mechanisms
      by which BHV-1 infection of respiratory epithelial cells contributes to the
      recruitment and activation of bovine polymorphonuclear neutrophils (PMNs) in
      vitro. Primary cultures of bovine bronchial epithelial (BBE) cells were infected
      with BHV-1 and assessed for cytokine expression by real-time PCR. We found that
      BHV-1 infection elicits a rapid IL-1, IL-8 and TNF-alpha mRNA response by BBE
      cells. Bovine PMNs exhibited greater adherence to BHV-1 infected BBE cells than
      uninfected cells. The increased adherence was significantly reduced by the
      addition of an anti-IL-1beta antibody or human soluble TNF-alpha receptor (sTNF
      alphaR). Pre-incubation of bovine PMNs with conditioned media from BHV-1 infected
      BBE cells increased PMN migration, which was inhibited by addition of an anti-IL
      1beta antibody, sTNF-alphaR, or an IL-8 peptide inhibitor. Conditioned media from
      BHV-1 infected BBE cells activated bovine PMNs in vitro as demonstrated by PMN
      shape change, production of reactive oxygen species and degranulation. PMNs also
      exhibited increased LFA-1 expression and susceptibility to M. haemolytica LKT
      following incubation with BHV-1 infected BBE cell conditioned media. Our results
      suggest that BHV-1 infection of BBE cells triggers cytokine expression that
      contributes to the recruitment and activation of neutrophils, and amplifies the
      detrimental effects of M. haemolytica LKT.

PMID- 19406485
TI  - The hippocampal rate code: anatomy, physiology and theory.
AB  - Since the days of Cajal, the CA1 pyramidal cell has arguably received more
      attention than any other neuron in the mammalian brain. Hippocampal CA1 pyramidal
      cells fire spikes with remarkable spatial and temporal precision, giving rise to
      the hippocampal rate and temporal codes. However, little is known about how
      different inputs interact during spatial behavior to generate such robust firing
      patterns. Here, we review the properties of the rodent hippocampal rate code and
      synthesize work from several disciplines to understand the functional anatomy and
      excitation-inhibition balance that can produce the rate-coded outputs of the CA1
      pyramidal cell. We argue that both CA3 and entorhinal inputs are crucial for the
      formation of sharp, sparse CA1 place fields and that precisely timed and dominant
      inhibition is an equally important factor.

PMID- 19406486
TI  - Aroclor 1248 exposure leads to immunomodulation, decreased disease resistance and
      endocrine disruption in the brown bullhead, Ameiurus nebulosus.
AB  - The brown bullhead Ameiurus nebulosus is a species of the family Ictaluridae
      commonly used as a sentinel of environmental contamination. While these fish have
      been utilized for this purpose in areas contaminated with polychlorinated
      biphenyls (PCBs), few controlled, laboratory-based studies have been designed to
      document the effects of PCB mixtures in this species. Here, brown bullhead were
      exposed to the PCB mixture, Aroclor 1248, via intraperitoneal injection and the
      effects on immune function, plasma hormones and disease resistance were
      evaluated. Exposure to this mixture led to a decrease in bactericidal activity
      and circulating antibodies to Edwardsiella ictaluri present from a previous
      exposure to this pathogen. A subsequent E. ictaluri disease challenge led to
      significantly higher mortality in A1248 treated fish compared to vehicle-control
      fish. The mitogenic response to the T-cell mitogen, phytohemaglutinin-P, was
      increased compared to vehicle-control fish. The steroid hormone, cortisol, and
      the thyroid hormone, T3, were also significantly lower in A1248 exposed fish. In
      summary, we have validated a number of functional immune assays for application
      in brown bullhead immunotoxicity studies. Additionally, we have demonstrated that
      the PCB mixture (A1248) modulates both immune function and endocrine physiology
      in brown bullhead. Such data may compliment the interpretation of data yielded
      from applied field studies conducted in PCB contaminated aquatic ecosystems.

PMID- 19406487
TI  - Effects of binary mixtures of estrogen and antiestrogens on Japanese medaka
      (Oryzias latipes).
AB  - It is supposed that the estrogenic effects of estrogenic chemicals will be
      balanced by the presence of other endocrine-disrupting chemicals (EDCs) with
      different properties. However, little convincing research into this issue has
      been carried out to date. In the present study, the combined effects of EDCs with
      estrogenic and antiestrogenic activities were assessed using a 21-day
      reproduction assay with the Japanese medaka (Oryzias latipes) as an in vivo
      model. Natural estrogen (17beta-estradiol, E2) and the pharmaceutical substances
      letrozole and tamoxifen, which are both model antiestrogens, were tested as
      reference compounds individually and in combination. Exposure to E2 (200 ng/L)
      alone resulted in significant biological changes in paired fish, including
      impaired reproductive capacity and plasma vitellogenin induction. Upon coexposure
      with tamoxifen or letrozole (10, 50 and 250 microg/L), the effects of estrogen on
      some biomarkers (e.g., plasma vitellogenin concentration) could be neutralized to
      some extent, but the impairments in reproductive performance were hardly
      ameliorated or even became more severe. Since reproductive performance is a more
      holistic parameter with population-level relevance, the possibility that the
      effects of estrogenic chemicals can be cancelled out by the presence of
      antiestrogens in aquatic organisms should be questioned. Our observations also
      illustrate the importance of considering multiple endpoints at different
      biological levels of organisms for accurate and adequate assessment of the
      integrated effects of EDCs, especially in environmentally relevant exposure
      situations.

PMID- 19406488
TI  - Clinical pathways: adherence issues in complex older female patients with heart
      failure (HF).
AB  - HF is a leading health care concern, often under-recognized and under-treated in
      older women. Management of this complex condition frequently requires a
      multidisciplinary approach and a clinical pathway can be used to deliver
      coordinated care. This report is based on the intervention/treatment arm (n = 45)
      of a randomized controlled trial in older women who participated in a
      multidisciplinary clinic. We describe the development of a clinical pathway for
      HF and the variance reporting including factors affecting adherence with the
      pathway. Variances are patient or staff actions that did not meet the expected
      outcomes. Of the 45 intervention arm female patients, 5 were able to fully
      complete the program, meaning that all of the intended 12 visits were completed
      successfully. Thirteen women missed more than three clinic visits, and the rest
      attended most visits. Variance tracking identified that visits were interrupted
      most often by patient-related health issues, such as fatigue and pain, which may
      not be surprising given the expected multiple co-morbidities in this population.
      Transportation problems were identified as a barrier to attendance. Our study
      demonstrates that a clinical pathway can be implemented in an older, female
      population with HF. This report identifies some of the challenges and provides
      future recommendations for prospective pathway development.

PMID- 19406489
TI  - Obesity among Iranian old adult women in urban and rural areas in Guilan.
AB  - This study aimed to describe the prevalence of overweight and obesity in a
      population of women older than 50 years (50-83 years) in urban and rural areas in
      Guilan. A total number of 731 women aged 50 years and above were randomly
      selected from the urban area (n=420) and rural areas (n=291). Data on age,
      educational levels, employment status, parity, body weight and height were
      collected. Prevalence of overweight/obesity was higher among older women in the
      urban area than rural areas (82.1% vs. 66.1% p<0.0001). Overweight/obesity was
      not related to educational level in this population. In conclusion, these results
      showed that overweight and obesity is highly prevalent among older women in the
      urban and rural areas in Guilan. Obesity in old age is associated with a poor
      quality of life. Preventive measures may lessen the burden of disease and
      impaired quality of life associated with excess weight.

PMID- 19406490
TI  - Communicating bilateral coronary artery to pulmonary artery fistula with
      aneurysms.
AB  - Bilateral coronary artery to pulmonary artery fistula is very rare. We describe a
      70-year-old female patient with communicating bilateral coronary artery to
      pulmonary artery fistula identified on coronary angiography and coronary computed
      tomography angiography.

PMID- 19406491
TI  - Cardiovascular risk of the general population assessed through SCORE and CUORE
      charts: an extensive survey by the General Practitioners from Abruzzo, Italy.
AB  - BACKGROUND: Current European guidelines for coronary heart diseases (CHD)
      prevention recommend to base any intervention on individual's global risk
      evaluation. An extensive survey was conducted to evaluate the ten-year CHD risk
      of the general population of Abruzzo, Italy. METHODS: In 2007, all regional
      general practitioners (GPs) received educational intervention; software allowing
      immediate risk calculation and data transmission to the Region; economic
      incentives for participation. RESULTS: Overall, 78.6% of all GPs (n=873) assessed
      and reported the CHD risk of 155,900 individuals (31.6% of the population aged 40
      69 years with no history of CHD). Ninety seven GPs sent data on >90% of their
      patients (n=47,120), and analyses were based upon this restricted sample with
      lower potential for selection bias. According to Italian CUORE risk-scoring
      chart, the estimated prevalence of high-risk (>=20%) subjects for CHD was 5.0%
      (males=8.5%; females=1.6%). According to European SCORE chart, the estimated
      prevalence of subjects at high risk (>=5%) for fatal CHD was 8.6% (males=15.0%;
      females=2.3%). The agreement between SCORE and CUORE methods was moderate
      (kappa=0.51). CONCLUSIONS: Beyond epidemiological significance, the composite
      approach of the survey represents a promising intervention of CHD prevention, as
      almost one third of the target population was evaluated by GPs with subsequent
      implications for clinical practice. Among the key reasons for the high
      participation rate, educational interventions and economic incentives played a
      role, but software characteristics may have been crucial. Because no individual
      aged 40-49 years was considered at high risk using both CUORE and SCORE charts,
      their widespread use in such age class deserves discussion.

PMID- 19406492
TI  - Mechanisms of action and clinical implications of cardiac urocortin: a journey
      from the heart to the systemic circulation, with a stopover in the mitochondria.
AB  - The small peptide urocortin (Ucn) has the ability to protect the heart by
      reducing cardiac cell loss during myocardial ischemia/reperfusion, and improving
      post-ischemic cardiac performance. Although its mechanism of action is not
      clearly defined, investigations have revealed that Ucn acts through several
      kinase pathways, and modulates a group of genes which synergistically minimize
      mitochondrial damage. Besides cardioprotection, most recent findings suggest a
      role for Ucn as a cardiac biomarker. Serum Ucn levels may be clinically useful to
      diagnose cases of mild sub-lethal ischemia, lacking elevation of cardiac enzymes
      and electrocardiogram changes. Infusion of Ucn may also help reduce the extent of
      the iatrogenic ischemic/reperfusion injury, associated with cardioplegic arrest.

PMID- 19406494
TI  - Novel sodium channel SCN5A mutations in Brugada syndrome patients from Greece.
AB  - Brugada syndrome (BrS) is an inherited cardiac arrhythmia that may lead to sudden
      death in patients with structurally normal heart. Mutations in the alpha subunit
      of the cardiac sodium channel SCN5A gene are found in approximately 20% of cases.
      We clinically evaluated and genetically screened 7 patients that fully satisfied
      the clinical diagnostic criteria for the syndrome and 8 patients with a partial
      clinical diagnosis, for mutations in the SCN5A gene in order to explore the
      genetic status of BrS patients from Greece for whom there are no published data
      available. Genetic testing was positive in 3 out of the 7 patients with a
      definite diagnosis. The probands carried 1 nonsense (p.Trp301X) and 2 missense
      (p.Ala1949Pro and p.Arg808Cys) mutations. All 3 mutations were novel.
      Furthermore, genetic testing was negative in all 8 clinically suspected cases.
      Additionally, 10 single nucleotide polymorphisms (SNPs) were detected, 2 of which
      are novel. We report on the genetic status of BrS patients of Greek origin
      amongst whom novel SCN5A mutations were a frequent underlying cause of the
      syndrome.

PMID- 19406493
TI  - Relationship between renal function and outcomes in high-risk patients with non
      ST-segment elevation acute coronary syndromes: results from SYNERGY.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a risk factor for coronary heart
      disease and bleeding with antithrombotic therapy in patients with acute coronary
      syndromes (ACS). We evaluated the effect of renal function on efficacy and
      outcomes in high-risk patients with NSTE ACS in the SYNERGY trial. METHODS:
      Creatinine clearance (CrCl) at the time of randomization was analyzed as a
      continuous variable added to multivariable logistic regression models for 30-day
      death or MI, non-CABG-associated TIMI major bleeding, GUSTO severe bleeding, and
      transfusion in the overall study population, patients undergoing coronary
      angiography, and patients undergoing PCI. RESULTS: Of 9838 patients with a CrCl
      value, 70.6% (N=6950) had CrCl>=60 mL/min, 27.8% (N=2732) had CrCl 30-59 mL/min,
      and 1.6% (N=156) had CrCl<30 mL/min. No randomized treatment by CrCl interaction
      test was found to be statistically significant, suggesting renal insufficiency
      affected enoxaparin and unfractionated heparin outcomes similarly. After
      adjustment, CrCl was an independent predictor of 30-day death or MI (OR 1.06, 95%
      CI 1.03-1.09), TIMI major bleeding (OR 1.06, 95% CI 1.02-1.10), GUSTO severe
      bleeding (OR 1.10, 95% CI 1.03-1.17), and transfusion (OR 1.07, 95% CI 1.04
      1.11). CONCLUSIONS: Patients with CKD had higher rates of 30-day death or MI and
      bleeding than those without CKD, regardless of randomized antithrombin therapy.
      While this analysis suggests that there is a rise in bleeding events as CrCl
      falls for patients in either treatment group, it is unknown whether a reduction
      in dose would decrease bleeding risk.

PMID- 19406495
TI  - MELAS in the heart.

PMID- 19406496
TI  - Comparing subjective and objective measures of health: Evidence from hypertension
      for the income/health gradient.
AB  - Economists rely heavily on self-reported measures of health to examine the
      relationship between income and health. We directly compare survey responses of a
      self-reported measure of health that is commonly used in nationally
      representative surveys with objective measures of the same health condition. We
      focus on hypertension. We find no evidence of an income/health gradient using
      self-reported hypertension but a sizeable gradient when using objectively
      measured hypertension. We also find that the probability of false negative
      reporting is significantly income graded. Our results suggest that using commonly
      available self-reported chronic health measures might underestimate true income
      related inequalities in health.

PMID- 19406497
TI  - Polymeric heart valves: new materials, emerging hopes.
AB  - Heart valve (HV) replacements are among the most widely used cardiovascular
      devices and are in rising demand. Currently, clinically available devices are
      restricted to slightly modified mechanical and bioprosthetic valves. Polymeric
      HVs could represent an attractive alternative to the existing prostheses, merging
      the superior durability of mechanical valves and the enhanced haemodynamic
      function of bioprosthetic valves. After early unsatisfactory clinical results,
      polymeric HVs did not reach commercialization, mainly owing to their limited
      durability. Recent advances in polymers, nanomaterials and surface modification
      techniques together with the emergence of novel biomaterials have resulted in
      improved biocompatibility and biostability. Advances in HV design and fabrication
      methods could also lead to polymeric HVs that are suitable for long-lasting
      implantation. Considering all these progresses, it is likely that the new
      generation of polymeric HVs will find successful long-term clinical applications
      in future.

PMID- 19406498
TI  - An assessment of the pressure distribution exerted by a rider on the back of a
      horse during hippotherapy.
AB  - Hippotherapy employs locomotion impulses that are emitted from the back of a
      horse while the horse is walking. These impulses stimulate the rider's postural
      reflex mechanisms, resulting in training of balance and coordination. The aim of
      the present study was to assess the changes in magnitude and distribution of the
      contact pressure between the rider and the horse during a series of hippotherapy
      lessons. The monitored group, consisting of four healthy women (mean age 22.75
      years, mean body weight 59.75 kg, mean height 167.25 cm) without any previous
      horse riding experience, received five 20 minute-lessons lessons in a three-week
      period. Hippotherapy was given on a 15-year-old thoroughbred mare. An elastic pad
      (Novel Pliance System, 30 Hz, 224 sensors) was used for pressure magnitude
      evaluation. The maximum pressure value was increased (p<.05) in the event of a
      second measurement (5th lesson). The pressure exerted on the rider upon contact
      of the rear limbs was higher than upon contact of the front limbs (p<.01). The
      size of the center of pressure (COP) deviations in the anteroposterior direction
      reduced (p<.05) with the number of lessons received. With the growing experience
      of the participant, an increase in pressure occurred on contact of her body and
      the horse's back as well as in the stability of the COP movement.

PMID- 19406499
TI  - Interaction between HNF4A polymorphisms and physical activity in relation to type
      2 diabetes-related traits: results from the Quebec Family Study.
AB  - AIMS: To test for associations between type 2 diabetes mellitus (T2DM)-related
      traits and polymorphisms (SNPs) in the hepatocyte nuclear factor 4-alpha gene
      (HNF4A) in the Quebec Family Study cohort, and determine whether these
      associations are modulated by physical activity (PA). METHODS: Two HNF4A SNPs
      (rs1885088 G>A; rs745975 C>T), previously reported to be associated with T2DM,
      were studied in 528 non-diabetic subjects who underwent a 75g oral glucose
      tolerance test (OGTT). Glucose, insulin and C-peptide plasma levels, measured in
      the fasting state and during the OGTT, were used in the analysis. The amount
      (hours per week) of PA was assessed by questionnaire. RESULTS: The HNF4A
      rs1885088 SNP was not independently associated with T2DM-related traits, whereas
      the rs745975 was associated with fasting insulin, HOMA-IR and 2-h glucose levels
      (p<0.05 for all). Genotype by PA interactions were found for glucose homeostasis
      (p<0.0001) and insulin secretion (p<or=0.03). When subjects were stratified by PA
      level (according to the median value), we found that high level of PA (>2h/week)
      was associated with smaller glucose area under the curve (AUC) and 2-h glucose
      levels in rs1885088 A/A homozygotes and with lower fasting C-peptide and insulin
      AUC in rs745975 T/T homozygotes. CONCLUSION: These results indicate that the
      associations of HNF4A rs1885088 with glucose tolerance and rs745975 with insulin
      secretion are modulated by PA. Our finding therefore suggests that the effect of
      HNF4A polymorphisms on the risk of T2DM is influenced by PA.

PMID- 19406500
TI  - Robust real time eye tracking for computer interface for disabled people.
AB  - Gaze is a natural input for a Human Computer Interface (HCI) for disabled people,
      who have of course an acute need for a communication system. An efficient eye
      tracking procedure is presented providing a non-invasive method for real time
      detection of a subject eyes in a sequence of frames captured by low cost
      equipment. The procedure can be easily adapted to any subject and is adequately
      insensitive to changing of the illumination. The eye identification is performed
      on a piece-wise constant approximation of the frames. It is based on a discrete
      level set formulation of the variational approach to the optimal segmentation
      problem. This yields a simplified version of the original data retaining all the
      information relevant to the application. Tracking is obtained by a fast update of
      the optimal segmentation between successive frames. No eye movement model is
      required being the procedure fast enough to obtain the current frame segmentation
      as one step update from the previous frame segmentation.

PMID- 19406501
TI  - Long-term survivors of more than 5 years in advanced non-small cell lung cancer.
AB  - BACKGROUND: The aim of this study is to evaluate the rate of long-term survival
      of more than 5 years in advanced non-small cell lung cancer (NSCLC). METHODS: One
      hundred and twenty-four patients with advanced NSCLC treated with chemotherapy
      from September 2002 to October 2003 were reviewed. RESULTS: Ten (8%) patients
      survived for more than 5 years. The median survival time (MST) for the 10
      patients was 61.5 months, ranging from 60.1 to 81.0 months. All of the 10
      patients had performance status (PS) 0 or 1 and adenocarcinoma. As the initial
      treatment, 9 patients were treated with a platinum-containing chemotherapy
      [median progressive free survival (PFS), 10.7 months] and 8 patients received
      gefitinib as the second or third line chemotherapy (median PFS, 28.7 months).
      Nine patients received cytotoxic agents after first line chemotherapy (median
      duration of the chemotherapy, 22.4 months). A mean regimen of chemotherapy was
      three (range, 1-8). Re-challenge of gefitinib was performed in 2 patients, and
      surgical resection of solitary brain metastasis was performed as the initial
      treatment in 2 patients. CONCLUSION: Our results suggest that good performance
      status, adenocarcinoma and EGFR-TKI therapy play an important role in the long
      term survivors of more than 5 years.

PMID- 19406502
TI  - How feasible is the biological control of coral diseases?
AB  - The worldwide decline of coral reefs necessitates the development of strategies
      aimed at controlling coral disease. As a result, various biological approaches
      are being considered as tools for coral disease management. For example, phage
      therapy has been shown to be effective in removing pathogens under laboratory
      conditions, showing promise for the treatment of specific pathogens; in addition,
      mutualistic bacteria compete with pathogens and produce antibiotics, properties
      that are both known to be important for biological control. Here we evaluate the
      probiotic potential of native mutualistic bacteria as a means of controlling
      coral diseases caused by opportunistic pathogens or their consortia. Monitoring
      native coral-associated microbiota for functions associated with resistance to
      pathogens could also serve as an additional indicator of reef health.

PMID- 19406503
TI  - Commentary: Exploring more dermatology education for medical students. Who, what,
      where, when, why, and how?

PMID- 19406505
TI  - Clinical characteristics of a series of 302 French patients with hidradenitis
      suppurativa, with an analysis of factors associated with disease severity.
AB  - BACKGROUND: Factors associated with the severity of hidradenitis suppurativa (HS)
      are not known. OBJECTIVE: We sought to identify factors associated with the
      severity of HS. METHODOLOGY: The severity of disease in a series of 302
      consecutive patients with HS was assessed using the Sartorius score. RESULTS:
      Atypical locations were more common in men than in women (47.1% vs 14.8%; P <
      .001). Men also had more severe disease (median Sartorius score: 20.5 vs 16.5; P
      = .02). Increased body mass index (P < .001), atypical locations (P = .002), a
      personal history of severe acne (P = .04), and absence of a family history of HS
      (P = .06) were associated with an increased Sartorius score. The Sartorius score
      was highly correlated with the intensity and duration of pain and suppuration
      (all P values < .001). LIMITATIONS: The referral center base of the study may
      have biased recruitment. CONCLUSION: Our data showed a significant association
      between the severity of HS and several clinical and behavioral factors.
      Prospective studies are needed to confirm the prognostic role of these factors.

PMID- 19406504
TI  - Metal deposition in calcific uremic arteriolopathy.
AB  - BACKGROUND: Calcific uremic arteriolopathy (CUA) is an often fatal disease that
      affects patients with end-stage renal disease. Although animal studies support a
      role for metals in the pathogenesis of CUA, metal accumulation in human tissue
      has not been previously evaluated. OBJECTIVE: We sought to evaluate metal
      deposition in CUA. METHODS: Twelve histologically proven cases of CUA were
      identified from our dermatopathology database. Five skin biopsy specimens from
      patients with chronic kidney disease exposed to gadolinium contrast but without
      CUA were used as controls. Quantification of metals including iron, aluminum, and
      gadolinium in the lesional skin was performed using inductively coupled mass
      spectrometry. RESULTS: Seven patients had documented exposure to gadolinium-based
      contrast in the 2 years before CUA. Three of them had concurrent nephrogenic
      systemic fibrosis. Highly significant quantities of iron (P = .03) and aluminum
      (P = .0002) were detected in CUA specimens compared with controls. Significant
      amounts of gadolinium were present in several CUA biopsy specimens. LIMITATIONS:
      Observational, retrospective study design and small sample size are limitations.
      CONCLUSION: Tissue iron and aluminum content is increased in CUA. A significant
      amount of gadolinium is also present in some CUA specimens. Based on animal
      studies that strongly implicate metals in the pathogenesis of CUA, our data
      suggest that metal deposition should be considered in the pathogenesis of human
      CUA.

PMID- 19406506
TI  - Development of a two-step method for the diagnosis of melanoma by reflectance
      confocal microscopy.
AB  - BACKGROUND: Reflectance confocal microscopy (RCM) has been shown to improve
      accuracy in the differentiation of nevus from melanoma, but only a few studies
      have evaluated both melanocytic lesions (ML) and non-ML. OBJECTIVE: We sought to
      develop an algorithm for the in vivo diagnosis of skin tumors by RCM. METHODS: In
      143 patients we evaluated 154 skin tumors (100 melanocytic, 54 nonmelanocytic) by
      RCM before their excision. We analyzed RCM features on stored images and
      performed univariate and multivariate analyses to determine the association of
      RCM features with tumor types. RESULTS: Four confocal features differentiated ML
      from non-ML: cobblestone pattern of epidermal layers, pagetoid spread, mesh
      appearance of the dermoepidermal junction, and the presence of dermal nests.
      Within ML, the presence of roundish suprabasal cells and atypical nucleated cells
      in the dermis was associated with melanoma, and the presence of edged papillae
      and typical basal cells was associated with nevi. Based on the correlation of RCM
      features with dermatoscopy and histology, we developed a two-step algorithm for
      the diagnosis of skin tumors by RCM. LIMITATIONS: This is a preliminary study,
      and the results must be validated in further studies with a larger number of
      cases. CONCLUSION: RCM appears to be helpful in improving the presurgical
      diagnosis of difficult skin tumors.

PMID- 19406507
TI  - Expert consensus guidelines for stocking of antidotes in hospitals that provide
      emergency care.
AB  - STUDY OBJECTIVE: We developed recommendations for antidote stocking at hospitals
      that provide emergency care. METHODS: An expert panel representing diverse
      perspectives (clinical pharmacology, clinical toxicology, critical care medicine,
      clinical pharmacy, emergency medicine, internal medicine, pediatrics, poison
      centers, pulmonary medicine, and hospital accreditation) was formed to create
      recommendations for antidote stocking. Using a standardized summary of the
      medical literature, the primary reviewer for each antidote proposed guidelines
      for antidote stocking to the full panel. The panel used a formal iterative
      process to reach their recommendation for the quantity of an antidote that should
      be stocked and the acceptable period for delivery of each antidote. RESULTS: The
      panel recommended consideration of 24 antidotes for stocking. The panel
      recommended that 12 of the antidotes be available for immediate administration on
      patient arrival. In most hospitals, this period requires that the antidote be
      stocked in the emergency department. Another 9 antidotes were recommended for
      availability within 1 hour of the decision to administer, allowing the antidote
      to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt
      delivery of antidotes. The panel identified additional antidotes that should be
      stocked by the hospital but are not usually needed within the first hour of
      treatment. The panel recommended that each hospital perform a formal antidote
      hazard vulnerability assessment to determine the need for antidote stocking in
      that hospital. CONCLUSION: The antidote expert recommendations provide a tool to
      be used in creating practices for appropriate and adequate antidote stocking in
      hospitals that provide emergency care.

PMID- 19406508
TI  - [Strongyloides stercoralis infestation in an immunocompetent 82-year-old woman].
AB  - A laboratory finding of eosinophilia in patients with gastrointestinal symptoms
      should prompt the differential diagnosis of a parasitosis. The diagnosis is based
      on identification of larvae in three different stool samples. We report the case
      of an 82-year-old woman who was independent for instrumental and advanced
      activities of daily living and showed no risk factors for strongyloidiasis who
      was admitted to our service with diarrhoea and abdominal pain. Blood examination
      showed peripheral eosinophilia of 38%. Stool sample revealed Strongyloides
      stercoralis. In the patient's case history, we found similar clinical features
      with fluctuating eosinophilia over the previous 8 years. The patient was treated
      with albendazole, resulting in clinical improvement and elimination of
      eosinophilia.

PMID- 19406509
TI  - [Optimising resources. Management of prescriptions].

PMID- 19406510
TI  - [Trends in the use of five antibiotics in the Province of Segovia (Spain) from
      2003 to 2006].

PMID- 19406511
TI  - [Importance and role of the department of family medicine in the faculty of
      medicine: an international perspective].

PMID- 19406512
TI  - [Commercial criteria or epidemiological criteria in anti-tetanus vaccination?].

PMID- 19406513
TI  - [Can we improve the implementation of clinical practice guidelines?].

PMID- 19406514
TI  - [Marfan's syndrome].

PMID- 19406516
TI  - [Oxazolidinones, glycopeptides and cyclic lipopeptides].
AB  - A review of the chemical structure, pharmacokinetics, spectrum of activity,
      clinical use, and adverse effects of oxazolidinones (linezolid), glycopeptides,
      and cyclic lipopeptides (daptomycin) is presented. Oxazolidinones inhibit protein
      synthesis, and glycopeptides and cyclic lipopeptides act against the bacterial
      cell wall. The antibacterial spectrum of these agents covers gram-positive
      pathogens, including multiresistant microorganisms. Absorption of linezolid is
      approximately 100% and it can be administered orally or intravenously. Linezolid
      is cleared by both the kidney and liver; thus, dose adjustments are not needed in
      patients with renal or hepatic failure. Oral absorption of glycopeptides is
      minimal, and excretion occurs through the kidneys. Daptomycin has fast, potent
      bactericidal activity, and can only be administered intravenously. The main
      clinical indication for these antimicrobial agents is the treatment of infections
      caused by multiresistant gram-positive pathogens, particularly staphylococci.
      Linezolid can cause anemia, thrombocytopenia, and gastrointestinal side effects,
      especially in prolonged therapy. The main side effect of vancomycin is
      nephrotoxicity, and teicoplanin can cause fever. Daptomycin is a safe antibiotic,
      with myotoxicity being the most relevant side effect.

PMID- 19406518
TI  - [Diarrhea: atypical presentation of Q fever].

PMID- 19406517
TI  - [An HIV-positive homosexual man with fever and a skin lesion].

PMID- 19406519
TI  - Atazanavir-related renal insufficiency without concurrent tenofovir.

PMID- 19406520
TI  - [Abdominal and retroperitoneal abscesses in a patient with bladder carcinoma
      receiving BCG therapy].

PMID- 19406521
TI  - [Adequacy assessment of antibiotic prophylaxis in orthopedic and traumatologic
      surgery].
AB  - INTRODUCTION: Antibiotic prophylaxis is an essential strategy for preventing
      surgical wound infection. This study assesses the adequacy of surgical antibiotic
      prophylaxis in trauma and orthopedic patients. METHODS: Cross-sectional study
      including consecutive patients who underwent hip or knee replacement, or spinal
      surgery. Sample estimation was based on 95% confidence, 5% precision, an overall
      adequacy of 85%, and assuming a loss of 5%. Thus, 206 patients were required. The
      appropriateness of the indication, time of administration, administration route,
      and dose according to the hospital protocol was assessed. The cumulative
      incidence of surgical site infection at discharge was determined. RESULTS: A
      total of 221 patients were included, 33.5% men and 66.5% women; mean age was 61.1
      (SD=14.1) for men and 67.1 (SD=12.4) for woman (P<0.05). Antibiotic prophylaxis
      was indicated in all patients. Overall adequacy of prophylaxis according to the
      hospital protocol was 89.1%. Cumulative incidence of surgical wound infection at
      discharge was 3.2%. There was no association between the adequacy of antibiotic
      prophylaxis and surgical site infection (P>0.05). CONCLUSIONS: The adequacy of
      postoperative antibiotic prophylaxis was high in this study, but it can be
      improved.

PMID- 19406522
TI  - [Effectiveness of systematic investigation for Group B Streptococcus in urine
      samples to identify colonized pregnant women].
AB  - OBJECTIVE: To evaluate the effectiveness of systematic investigation for Group B
      Streptococcus (GBS) in urine samples to detect colonization in pregnant women.
      METHODS: This study included 1036 pregnant women whose urine samples were
      cultured in our laboratory during 2006. Any colony consistent with GBS was
      identified in urine or in rectovaginal samples submitted for screening of GBS
      colonization. RESULTS: GBS was recovered in urine samples from 111 of the 1036
      women (10.7%), and in 77 of them bacterial count was <10(4) colony forming
      units/mL. Screening for GBS in rectovaginal samples was performed in 841 of the
      925 pregnant women who did not have GBS bacteriuria (10.1% positive results) and
      in 61 of the 111 with GBS bacteriuria (60.7% positive results; no significant
      differences were found when results were stratified by colony count). Estimated
      rectovaginal colonization was 15.4%, and colonization exclusively detected in
      urine was 4.2%. Only 30% of pregnant women with GBS bacteriuria, but negative
      antenatal screening cultures who were admitted to our hospital for delivery
      received intrapartum antibiotic prophylaxis. CONCLUSIONS: Systematic
      investigation of the presence of GBS in urine samples from pregnant women
      improves the detection of carriers who are candidates for receiving intrapartum
      prophylaxis to prevent perinatal GBS infection, when compared with rectovaginal
      screening culture in the last trimester of gestation alone.

PMID- 19406523
TI  - [Comparison between agar dilution and three other methods for determining the
      susceptibility of 228 clinical isolates of non-fermenting gram-negative rods].
AB  - INTRODUCTION: Susceptibility testing for non-fermenting gram-negative rods
      (NFGNR) is problematic; valid methods are needed for this purpose. METHODS: In
      this study, 228 NFGNR clinical isolates were evaluated, including 85
      Acinetobacter spp., 80 Stenotrophomonas maltophilia, 50 Pseudomonas aeruginosa,
      and 13 other species (8 Ralstonia pickettii and 5 Burkholderia cepacia). Agar
      dilution was used as the reference method, and results were compared with those
      obtained by disk diffusion, Etest, and microdilution performed with the VITEK 2
      Compact System. RESULTS: The disk method was unacceptable for S. maltophilia and
      P. aeruginosa, in the latter organism, mainly because of poor agreement in the
      colistin results. Nonetheless, the disk method is valid for Acinetobacter spp.
      and the remaining NFGNRs. The VITEK 2 Compact System yielded poor results for
      piperacillin-tazobactam, tigecycline, and ceftazidime in S. maltophilia. There
      were minor discrepancies with the VITEK 2 Compact system and the Etest for
      tigecycline in Acineobacter spp. and S. maltophilia, likely because of the
      differing composition of the Muller-Hinton agar lots. Hence, Etest results should
      be interpreted with caution. CONCLUSION: The disk diffusion method is inadequated
      for S. maltophilia. This method is unacceptable for testing colistin in P.
      aeruginosa. The methods Vitek 2 Compact System and Etest show minor discrepancies
      for testing S. maltophilia and Acinetobacter spp. for tigecycline.

PMID- 19406524
TI  - [Syphilitic panuveitis in an HIV-infected patient after immune restoration].

PMID- 19406525
TI  - [HIV-positive patient with hypercalcemia and normal PTH].

PMID- 19406526
TI  - [Congenital Chagas disease in a newborn of a Bolivian mother].

PMID- 19406527
TI  - [Increases in Clostridium difficile-related mortality rates in Spain (1999
      2006)].

PMID- 19406528
TI  - [Impact of infection on mortality in burn patients. Multivariate study in 1,773
      intensive care unit patients].
AB  - INTRODUCTION: Infections may play an important role in mortality in burn
      patients, but this impact is not manifested in multivariate analyses that
      calculate the probability of death on admission. PATIENTS AND METHODS: In a
      cohort of 1,773 ICU patients, logistic regression analysis was used to determine
      the prognostic factors for death. Subsequently, the cohort was divided into 2
      groups according to length of ICU stay: 1-10 days or more than 10 days. The
      groups contained a similar number of patients and the analysis was repeated in
      each one. RESULTS: Overall mortality in the 1,773 patients was 12.2%. In the
      stratified analysis mortality was 8.5% for the 890 patients who were in the ICU
      for 10 days or less and 15.8% for the 883 who stayed longer. The prognostic
      factors for death in the 2 groups were very different and had to be studied
      separately. In the group with a shorter ICU stay, the prognostic factors were
      similar to those of the entire cohort (eg, age, burned body surface area); in the
      group with a longer stay, these factors lost power and other factors, such as
      bacteraemia and pneumonia, gained significance. CONCLUSIONS: Estimation of the
      risk of death in ICU burn patients should be re-evaluated at 10 days after
      admission.

PMID- 19406529
TI  - [Comparative activity of daptomycin against clinical isolates of methicillin
      resistant Staphylococcus aureus and coagulase-negative staphylococci].
AB  - INTRODUCTION: The objective of this study was to determine the in vitro activity
      of daptomycin and other agents against methicillin-resistant Staphylococcus
      aureus (MRSA) isolates from several sources and coagulase-negative staphylococci
      (CoNS) from clinically significant blood cultures. METHODS: We tested a total of
      1186 staphylococci isolates (755 MRSA and 431 CoNS) collected as part of a
      multicenter surveillance program for antimicrobial resistance (VIRA study) from
      40 medical centers throughout Spain between 2001 and 2006. Broth microdilution
      tests were performed according to the Clinical and Laboratory Standards Institute
      guidelines. RESULTS: Most MRSA isolates were resistant to ciprofloxacin (96%) and
      erythromycin (79.7%). Daptomycin yielded a MIC(50)/MIC(90) of 0.5/1microg/mL in
      MRSA, compared with 1/2microg/mL for linezolid, vancomycin, and teicoplanin.
      Daptomycin MICs were in the range of < or =0.125-2microg/mL. Only 1 MRSA strain
      had a reproducible daptomycin MIC of 2microg/mL. Among CoNS isolates, the MIC
      range for daptomycin was < or =0.125-1microg/mL. Daptomycin was equally active
      against oxacillin-susceptible and oxacillin-resistant strains. CONCLUSION:
      Daptomycin was highly active against the staphylococci isolates studied. The
      activity of this agent was not affected by resistance to other antibiotics such
      as oxacillin, teicoplanin, linezolid, ciprofloxacin, or gentamicin. These data
      suggest that daptomycin may be useful for the treatment of severe infection
      caused by MRSA or CoNS.

PMID- 19406530
TI  - [Application of an automatic nucleic acid extraction method to improve the
      detection of Chlamydia trachomatis].

PMID- 19406532
TI  - [Paired case-control design and data analysis].

PMID- 19406531
TI  - [Prevalence of neural tube defects in Asturias (Spain): impact of prenatal
      diagnosis].
AB  - OBJECTIVE: To describe the frequency and prevalence trend for neural tube defects
      (NTD) (anencephaly, spina bifida and encephalocele) in Asturias (Spain), as well
      as the impact of prenatal diagnosis programs. METHODS: All cases of NTD in births
      and induced abortions were studied, using data from the Registry of Congenital
      Defects of Asturias for 1990-2004. Total and birth prevalence rates were
      calculated. RESULTS: The prevalence of NTD for 1990-2004 was 12.2 per 10,000
      births (5.9 anencephaly, 5.0 spina bifida and 1.3 encephalocele) and showed a
      slightly decreasing trend due to a significant decline in spina bifida
      prevalence. The prevalence of anencephaly and encephalocele remained stable. The
      percentage of induced abortions after prenatal diagnosis among all NTD was 88%
      (anencephaly 96.7%, spina bifida 80% and encephalocele 84.6%), leading to a very
      low birth prevalence (1.4 per 10,000) for the entire period. CONCLUSIONS: The
      total prevalence of spina bifida has decreased in the last 15 years in Asturias.
      Secondary prevention through prenatal diagnosis and interruption of affected
      pregnancies have resulted in a marked decrease in NTD at birth. The
      recommendation of periconceptional use of folic acid seems not to have achieved
      the desired effect.

PMID- 19406533
TI  - [Sexual and reproductive health in Spain].

PMID- 19406534
TI  - [An erroneous citation linked to the vaccine cold chain].

PMID- 19406536
TI  - [Pneumocystis pneumonia in two breast cancer patients treated with docetaxel: an
      unusual adverse event of chemotherapy].
AB  - We report two cases of pneumocystis pneumonia in patients receiving chemotherapy
      for breast cancer. These case series emphasize the frailty of the patients as the
      causative role for occurrence of this uncommon complication of chemotherapy in
      breast cancer. We remind the importance of screening for unusual adverse events
      in frail patients receiving chemotherapy.

PMID- 19406535
TI  - Synthesis and cytotoxic activity of alpha-santonin derivatives.
AB  - Ten alpha-santonin derivatives were synthesized in moderate to high yields. Four
      derivatives namely 10alpha-acetoxy-3-oxo-1,7alphaH,6,11betaH-guai-4-en-6,12-olide
      (2), isofotosantonic acid (3), 10alpha-hydroxy-3-oxo-1,7alphaH,6,11betaH-guai-4
      en-6,12-olide (4), and lumisantonin (5), were prepared by different photochemical
      reactions using alpha-santonin (1) as starting material. These transformations
      were carried out in either anhydrous acetic acid, acetic acid/water (1:1 v/v) or
      acetonitrile, using different types of reactors and ultraviolet light sources.
      Treatment of alpha-santonin (1) with lithium diisopropyl amide (LDA) followed by
      capture of the organolithium with phenyl selenium chloride produced the compound
      3-oxo-7alphaH,6betaH,11-(phenylselenyl)-eudesma-1,4-dien-6,12-olide (6).
      Subsequent treatment of compound 6 with hydrogen peroxide gave 3-oxo
      7alphaH,6betaH-eudesma-1,4,11-trien-6,12-olide (7). Photochemical reaction of
      compound 7 led to the formation of 11,13-dehydrolumisantonin (8) and 10alpha
      acetoxy-3-oxo-1,7alphaH,6betaH-guai-4,11-dien-6,12-olide (9). Sodium borohydride
      reduction of compounds 2 and 4 afforded the derivatives 10alpha-acetoxy-3beta
      hydroxy-1,7alphaH,6,11betaH-guai-4-en-6,12-olide (10) and 3beta,10alpha-hydroxy
      1,7alphaH,6,11betaH-guai-4-en-6,12-olide (11). The cytotoxicity of the
      synthesized compounds were evaluated against the cancer cell lines HL-60
      (leukemia), SF-295 (central nervous system), HCT-8 (colon), MDA-MB-435
      (melanoma), UACC-257 (melanoma), A549 (lung), OVACAR-8 (ovarian), A704 (renal),
      and PC3 (prostate). The compounds with higher activity, possessing IC(50) values
      in the range of 0.36-14.5 microM, showed as common structural feature the
      presence of an alpha-methylidene-gamma-butyrolactone moiety in their structures.
      The biological assays conducted with normal cells (PBMC) revealed that the
      compounds are selective against cancer cell lines. The modified lactones seem to
      be interesting lead structures towards anticancer drug development.

PMID- 19406538
TI  - Character of distracted bone in irradiated canine mandibles and
      electrophysiological changes in the inferior alveolar nerve.
AB  - Our aim was to explore the character of distracted bone in irradiated canine
      mandibles and the electrophysiological changes in the irradiated inferior
      alveolar nerve (IAN). Twelve Chinese dogs were studied, 10 of which were given
      unilateral irradiation of (60)Co in the mandible with a total dose of 22.8Gy in
      four 5.7Gy fractions (biologically equivalent to 50Gy/25 fractions) (experimental
      group). The other two dogs were not irradiated and served as controls. All had a
      bilateral corticotomy 3 months after irradiation. After a 1-week latency period
      distraction of the mandible was activated at a rate of 0.5mm twice daily for 10
      days, followed by a consolidation phase of 8 weeks. New bone was assessed by
      radiographic, histological, and single-photon electron computed tomographic
      (SPECT) analysis. The IAN was analysed electrophysiologically. One dog in the
      experimental group was excluded from the study with anaesthetic problems. After 8
      weeks of consolidation there was no difference between the percentage area of new
      bone in the two groups. New bone was more mature and organised in the control
      group than in the experimental group. SPECT analysis showed that there was active
      osteogenic activity in dogs in the experimental group. The action potential of
      the IAN showed corresponding changes during the irradiation and distraction
      processes. We conclude that distraction osteogenesis is feasible in previously
      irradiated canine mandibles and IAN.

PMID- 19406537
TI  - [Follow-up with the assistance of TB-info software of 208 tuberculosis patients
      who were treated in 2004].
AB  - INTRODUCTION: The impact of the TB-info software was assessed on the care of
      patients treated with antituberculosis regimen (ATT). METHODS: Cohort study of
      patients with tuberculosis who received an ATT in 2004 in two hospitals and five
      medical centres in Paris. Follow-up was implemented with the TB-info software.
      Data were compared to those of the 1999-2003 cohort. RESULTS: Two hundred and
      nine ATT were initiated in 2004, with a mean duration of 7.2 months. Demographic
      and clinical data reflected this population precariousness: 79% were foreign
      born, 25% lived in institutions and half of them had no or unusual health
      insurance. Compared to the previous cohort, viral co-infections were tested in
      more than 80% cases and showed association with HIV, HBV or HCV in 11, 10 and 5%
      of the patients, respectively. Twenty-one patients were lost for follow-up (11%)
      and 76% of the smear-positive pulmonary tuberculosis therapies were declared
      successful but only 34% were declared cured with the WHO criteria. CONCLUSION:
      Analysis of the data obtained with TB-info software showed an improvement of
      tuberculosis patients care with more co-infection tested and less lost for follow
      up. These results confirm the usefulness of this software for patients care and
      assessment of physicians practice in France.

PMID- 19406539
TI  - The effect of interspinous implant surgery on back surface shape and radiographic
      lumbar curvature.
AB  - BACKGROUND: Interspinous process implants, used to augment lumbar spine surgery,
      putatively induce a local segmental lumbar kyphosis yet few investigations
      outline the effect in vivo on thoracolumbar sagittal curvature. Changes in lumbar
      skeletal alignment and posture have traditionally relied upon radiographic and
      back surface spinal curvature measurements, respectively. METHODS: Lumbar
      lordosis curvature in 10 healthy subjects (6F, 4M; mean age 36 years) and 10
      interspinous implant lumbar surgery patients (5F, 5M; mean age 51 years) was
      assessed with rasterstereography at baseline and at 6 weeks. Skeletal lumbar
      lordosis in standing was measured from lateral erect radiography pre- and 6 weeks
      post-operatively in the surgical cohort, and compared to angulation obtained for
      surface lordosis curvature derived from rasterstereography. FINDINGS: Repeatable
      measurement of standing lumbar lordosis from rasterstereographic back shape
      imaging in healthy volunteers and lumbar surgery cases was demonstrated.
      Reductions of 0.6 (NS) in healthy and 3.1 (significant, P<0.001) in surgical
      subjects were recorded for surface lumbar lordosis angle between the 6 week time
      points. Slight flattening of the segmental angle and regional lordosis after DIAM
      surgery was revealed by radiography. Skeletal and surface lumbar lordosis changes
      were uncorrelated preoperatively (rho=0.28) and postoperatively (rho=0.26).
      INTERPRETATION: Rasterstereography is sensitive in assessing lumbar lordosis
      changes in healthy and lumbar surgical individuals over time. Surgery with DIAM
      for lumbar pathology may result in an initial mild flattening of lordosis. Serial
      investigations of spinal curvature after surgery with DIAM interspinous implant
      are warranted in order to better understand the time-course of spinal posture
      changes of such cases.

PMID- 19406540
TI  - Effects of arsenic on nitrate metabolism in arsenic hyperaccumulating and non
      hyperaccumulating ferns.
AB  - This study investigated the effects of arsenic on the in vitro activities of the
      enzymes (nitrate reductase and nitrite reductase) involved in nitrate metabolism
      in the roots, rhizomes, and fronds of four-month old Pteris vittata (arsenic -
      hyperaccumulator) and Pteris ensiformis (non-arsenic-hyperaccumulator) plants.
      The arsenic treatments (0, 150, and 300 microM as sodium arsenate) in hydroponics
      had adverse effects on the root and frond dry weights, and this effect was more
      evident in P. ensiformis than in P. vittata. Nitrate reductase and nitrite
      reductase activities of arsenate-treated plants were reduced more in P.
      ensiformis than in P. vittata. This effect was accompanied by similar decreases
      in tissue NO(3)(-) concentrations. Therefore, this decrease is interpreted as
      being indirect, i.e., the consequence of the reduced NO(3)(-) uptake and
      translocation in the plants. The study shows the difference in the tolerance
      level of the two Pteris species with varying sensitivity to arsenic.

PMID- 19406541
TI  - Definition and classification of CKD: the debate should be about patient
      prognosis--a position statement from KDOQI and KDIGO.

PMID- 19406542
TI  - Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis
      of randomized and observational studies.
AB  - BACKGROUND: Acute kidney injury (AKI) after coronary artery bypass grafting
      (CABG) is associated with significant morbidity and mortality. Controversy exists
      regarding whether an off-pump technique can reduce post-CABG renal injury. STUDY
      DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Adult patients
      undergoing CABG. SELECTION CRITERIA FOR STUDIES: MEDLINE, EMBASE, Cochrane Renal
      Library, and Google Scholar were searched in May 2008 for randomized controlled
      trials (RCTs) and observational studies comparing off-pump CABG (OPCAB) with
      conventional CABG (CAB) for renal outcomes. Studies involving patients on long
      term renal replacement therapy (RRT) were excluded. INTERVENTION: OPCAB.
      OUTCOMES: Primary outcomes were overall AKI and AKI requiring RRT. RESULTS: 22
      studies (6 RCTs and 16 observational studies) comprising 27,806 patients met the
      inclusion criteria. The pooled effect from both study cohorts showed a
      significant reduction in overall AKI (odds ratio [OR], 0.57; 95% confidence
      interval [CI], 0.43 to 0.76; P for effect < 0.001; I(2) = 67%; P for
      heterogeneity < 0.001) and AKI requiring RRT (OR, 0.55; 95% CI, 0.43 to 0.71; P
      for effect < 0.001; I(2) = 0%; P for heterogeneity = 0.5) in the OPCAB group
      compared with the CAB group. In RCTs, overall AKI was significantly reduced in
      the OPCAB group (OR, 0.27; 95% CI, 0.13 to 0.54); however, no statistically
      significant difference was noted in AKI requiring RRT (OR, 0.31; 95% CI, 0.06 to
      1.59). In the observational cohort, both overall AKI (OR, 0.61; 95% CI, 0.45 to
      0.81) and AKI requiring RRT (OR, 0.54; 95% CI, 0.40 to 0.73) were significantly
      less in the OPCAB group. RCTs were noted to be underpowered and biased toward
      recruiting low-risk patients. Sensitivity analysis restricted to good-quality
      studies showed a significant reduction in AKI. LIMITATIONS: Lack of uniform AKI
      definition in the included studies, heterogeneity for overall AKI outcome.
      CONCLUSIONS: Analysis of the current evidence suggests a reduction in AKI using
      the OPCAB technique; however, studies lack consistency in defining AKI. Available
      RCTs are underpowered to detect a difference in AKI requiring RRT; evidence from
      observational studies suggests a reduction in RRT requirement. Future studies
      should apply a standard definition of AKI and target a high-risk population.

PMID- 19406543
TI  - Tacrolimus therapy in adults with steroid- and cyclophosphamide-resistant
      nephrotic syndrome and normal or mildly reduced GFR.
AB  - BACKGROUND: In a proportion of adults with steroid-resistant nephrotic syndrome
      (SRNS), intravenous cyclophosphamide therapy fails. Tacrolimus may be a promising
      alternative to cyclophosphamide for such patients. STUDY DESIGN: Prospective
      observational study. SETTING & PARTICIPANTS: 19 adults with SRNS (6 with minimal
      change nephropathy, 8 with focal segmental glomerulosclerosis [FSGS], and 5 with
      mesangioproliferative glomerulonephritis) that did not respond to intravenous
      cyclophosphamide therapy were studied from January 2003 to September 2006. Oral
      tacrolimus was administered (target trough levels, 5 to 10 ng/mL) for 24 weeks,
      then reduced doses were given (target trough level, 3 to 6 ng/mL) for another 24
      weeks. FACTORS: Histopathologic types: minimal change nephropathy (n = 6), FSGS
      (n = 8), and mesangioproliferative glomerulonephritis (n = 5). OUTCOMES: 
      MEASUREMENTS: outcome variables included complete remission (decrease in daily
      proteinuria to protein < or = 0.3 g/d), partial remission (decrease in daily
      proteinuria to protein < 3.5 g/d but > 0.3 g/d), relapse (increase in daily
      proteinuria to protein > or = 3.5 g/d in patients who had partial or complete
      remission), change in kidney function, and tacrolimus dosing and serum levels.
      RESULTS: 17 patients completed at least 24 weeks of tacrolimus therapy. Complete
      remission was achieved in 11 patients (64.7%), and partial remission was achieved
      in 3 (17.6%). Complete or partial remission was achieved in 5 of 5 patients with
      minimal change nephropathy, 4 of 7 patients with FSGS, and 5 of 5 patients with
      mesangioproliferative glomerulonephritis. Primary resistance to tacrolimus was
      seen in 3 patients (17.6%), all with FSGS. Mean times to achieve partial and
      complete remission were 5.6 +/- 1.4 and 8.0 +/- 5.1 weeks, respectively. In
      patients who achieved complete or partial remission, 35.7% experienced relapse
      during follow-up (mean, 37.6 +/- 13.4 months). Two patients had doubling of serum
      creatinine levels, both with FSGS. LIMITATIONS: Observational study. CONCLUSIONS:
      Tacrolimus rapidly and effectively induced remission of SRNS in Chinese adults
      with disease refractory to treatment with intravenous cyclophosphamide. Treatment
      may be less effective in patients with FSGS.

PMID- 19406544
TI  - Hemodialysis facility-based quality-of-care indicators and facility-specific
      patient outcomes.
AB  - BACKGROUND: We evaluated whether incremental achievement of up to 8 facility
      quality goals was associated with improvement in facility-specific mortality and
      hospitalization rates. STUDY DESIGN: Prospective observational study. SETTING &
      PARTICIPANTS: 1,085 Fresenius Medical Care, North America facilities providing
      hemodialysis (HD) for 25 or more patients during January 2006. MEASUREMENTS: The
      facility average for the period up to December 31, 2006, was used to determine
      achievement of each goal for equilibrated Kt/V, missed HD treatments, hemoglobin
      level, bicarbonate level, albumin level, phosphorus level, fistulae, and HD
      catheters. Linear regression models were used to relate facility-wide achievement
      of goals with facility-specific hospital days and standardized mortality ratios.
      RESULTS: Most facilities (64%) achieved 2 to 4 of 8 goals, with only 8% meeting
      more than 5 quality goals. Achieving more than 5 goals averaged 3.5 fewer
      hospital days/patient-year and 20% lower standardized mortality ratios (all P <
      0.001). The incremental number of goals met also was associated with improvement
      in facility mortality (P < 0.001) and hospital days (P < 0.001). Catheter and
      albumin level goals were achieved least (6% and 9% of facilities, respectively),
      but they had the best outcomes. Facilities achieving more than 5 goals had older
      patients (64.0 versus 61.5 years; P < 0.001), fewer African American patients
      (16% versus 38%; P < 0.001), and fewer women (44% versus 46%; P = 0.003) compared
      with the average. LIMITATIONS: Observational design with residual confounding
      from unmeasured patient-, facility-, and treatment-related factors. CONCLUSIONS:
      Achieving more facility quality goals was significantly associated with better
      facility-based measurements of patient outcomes. Although these results do not
      establish a causal relationship, findings agree with the present practice of
      monitoring facility performance for continuous quality improvement.

PMID- 19406545
TI  - Investigating public preferences on 'severity of health' as a relevant condition
      for setting healthcare priorities.
AB  - This study examines the preferences of a sample of the UK general public over the
      allocation of healthcare resources. Preferences were elicited against scenarios
      where alternative patient groups are competing for limited resources. Respondents
      were asked to make a choice between either (i) groups described according to
      alternative descriptions for severity of health condition, or (ii) groups
      described according to a broader level of disadvantage (e.g. family income). The
      survey used a random-location quota sampling approach, and face-to-face interview
      techniques. Interviews were completed with 261 people in the Southampton area of
      England. Results showed that the majority or respondents wanted to divide
      resources equally between competing groups, giving at least equal preference to
      the more severely affected group, and the more disadvantaged group, regardless of
      a stated lower potential health gain in these groups compared to alternatives. In
      the severity of health question 60% indicated that a unit of health gain in a
      severely affected patient group was of greater social value to that same unit of
      health gain in a moderately affected patient group, all else equal. When
      described by level of disadvantage, 80% of respondents stated such a preference,
      which indicates that they attach a greater social value to a unit of health gain
      in a disadvantage patient group, compared to a more advantaged group, all else
      equal. When given an option to 'opt out' of a difficult decision, and to 'let
      others choose', very few respondents (5%) took that option, suggesting that the
      most common stated preference of dividing resource equally between groups may be
      a true preference, rather than respondents avoiding difficult decisions. When
      interpreting the findings from the survey, results suggest that preferences
      reported to give priority to those more severely affected by their health, may
      also be a reflection of a broader preference to treat those groups classed as
      worse-off, in empirical studies. Results are discussed against the growing
      importance of the empirical ethics literature, and the growing needs of health
      policy makers to seek out an empirical basis upon which to consider the
      challenges of setting priorities in healthcare.

PMID- 19406547
TI  - The performance and observation of action shape future behaviour.
AB  - The observation of other people's actions plays an important role in shaping the
      perceptual, cognitive, and motor processes of the observer. It has been suggested
      that these social influences occur because the observation of action evokes a
      representation of that response in the observer and that these codes are
      subsequently accessed by other cognitive systems to modify future behaviour. In
      the case of social search and movement tasks, the observation-evoked response
      code is thought to activate the same mechanisms that are activated following
      internally-generated response codes. In support of this hypothesis, the present
      study revealed that the magnitudes of the between-person inhibition of return
      (IOR) effects were correlated with within-person IOR effects. These findings
      provide substantial support for the link between observation-evoked response
      codes and social cognitive effects.

PMID- 19406546
TI  - Poverty-alleviation program participation and salivary cortisol in very low
      income children.
AB  - Correlational studies have shown associations between social class and salivary
      cortisol suggestive of a causal link between childhood poverty and activity of
      the stress-sensitive hypothalamic-pituitary-adrenocortical (HPA) system. Using a
      quasi-experimental design, we evaluated the associations between a family's
      participation in a large-scale, conditional cash transfer program in Mexico
      (Oportunidades, formerly Progresa) during the child's early years of life and
      children's salivary cortisol (baseline and responsivity). We also examined
      whether maternal depressive symptoms moderated the effect of program
      participation. Low-income households (income <20th percentile nationally) from
      rural Mexico were enrolled in a large-scale poverty-alleviation program between
      1998 and 1999. A comparison group of households from demographically similar
      communities was recruited in 2003. Following 3.5 years of participation in the
      Oportunidades program, three saliva samples were obtained from children aged 2-6
      years from intervention and comparison households (n=1197). Maternal depressive
      symptoms were obtained using the Center for Epidemiologic Studies-Depression
      Scale (CES-D). Results were that children who had been in the Oportunidades
      program had lower salivary cortisol levels when compared with those who had not
      participated in the program, while controlling for a wide range of individual-,
      household- and community-level variables. Reactivity patterns of salivary
      cortisol did not differ between intervention and comparison children. Maternal
      depression moderated the association between Oportunidades program participation
      and baseline salivary cortisol in children. Specifically, there was a large and
      significant Oportunidades program effect of lowering cortisol in children of
      mothers with high depressive symptoms but not in children of mothers with low
      depressive symptomatology. These findings provide the strongest evidence to date
      that the economic circumstances of a family can influence a child's developing
      stress system and provide a mechanism through which poverty early in life could
      alter life-course risk for physical and mental health disorders.

PMID- 19406549
TI  - A comparison of root caries diagnosis based on visual-tactile criteria and
      DIAGNOdent in vivo.
AB  - OBJECTIVES: This clinical study aimed to evaluate the validity of using
      DIAGNOdent in diagnosing root caries, and to assess the sensitivity and
      specificity of different cut-off DIAGNOdent values in assessing root caries with
      reference to visual-tactile criteria. METHODS: Exposed root surfaces were
      assessed by one examiner for root caries on 266 subjects using visual-tactile
      criteria and DIAGNOdent 2095 after dental scaling. Associations between
      DIAGNOdent values and visual-tactile diagnosis of root caries were determined.
      The cut-off level for statistical significance was 0.05. The sensitivity and
      specificity of DIAGNOdent with difference cut-off points were analysed compared
      to visual-tactile diagnosis of root caries. RESULTS: There was significant
      difference between DIAGNOdent values obtained from sound and carious root
      surfaces (p<0.001). On carious surfaces, active root caries obtained
      significantly higher DIAGNOdent values than inactive root caries (p<0.001). With
      increasing cut-off point DIAGNOdent values from 5 to 35, sensitivity decreased
      from 91.4% to 16.2% and specificity increased from 64.4% to 98.2%. A cut-off
      point of DIAGNOdent value between 5 and 10 produced the highest combined
      sensitivity and specificity. CONCLUSIONS: There was a significant difference in
      DIAGNOdent values between sound and carious root surfaces diagnosed by visual
      tactile criteria supporting the validity of DIAGNOdent for assessing root caries.
      A DIAGNOdent value between 5 and 10 produced the highest combined sensitivity and
      specificity when visual-tactile assessment of root caries was regarded as the
      criterion. These findings have implications in using and explaining DIAGNOdent
      values in assessing root caries.

PMID- 19406550
TI  - Enamel--a functionally graded natural coating.
AB  - OBJECTIVE: The aim of this study is to illustrate the graded proper properties of
      enamel from the outer (near occlusal surface) to the inner region (near enamel
      dentine junction) in a cross-sectioned surface and discuss how natural design
      achieve the graded functions. METHODS: Nanoindentation, Raman spectroscopes, and
      SEM were employed to compare the inner and outer regions of the cross-sectioned
      enamel from different angles, namely mechanical properties such as elastic
      modulus and hardness, indentation energy absorption ability, indentation creep
      ability, indentation residual stress distribution pattern, compositional
      differences, and microstructural differences. RESULTS: Inner enamel has lower
      elastic modulus and hardness but higher creep and stress redistribution abilities
      than outer counterpart, which is related to the gradual compositional change
      through the enamel. SIGNIFICANCE: Enamel can be regarded as a functionally graded
      natural biocomposite, which will require special attention using numerical
      analysis to fully appreciate the consequences of such a structure for the
      mechanical behaviour of teeth and restorations placed therein. Moreover, the
      smart design of nature can be a good model for us in functional graded
      materials/coatings design and development.

PMID- 19406551
TI  - Color measurement in dentistry.
AB  - Measurements of the color of natural and restorative craniofacial and dental
      materials have many important applications to clinical practice and research.
      Although the specification of color at the level of the human observer involves
      only three dimensions or a color difference between two colors, a more technical
      viewpoint of color determination involves the visible spectrum. This review will
      provide the link between the spectral, the three-dimensional and the color
      difference aspects of color and emphasize important geometrical aspects of all
      measuring systems. Further, evaluations of accuracy and precision of measuring
      systems and considerations of acceptability and perceptibility of a color
      difference are reviewed, and applications of color measurements to important
      appearance characteristics of natural and restorative materials are briefly
      introduced.

PMID- 19406552
TI  - Hemostasis in cardiac arrest patients treated with mild hypothermia initiated by
      cold fluids.
AB  - AIM OF THE STUDY: Application of mild hypothermia (32-33 degrees C) has been
      shown to improve neurological outcome in patients with cardiac arrest. However,
      hypothermia affects hemostasis, and even mild hypothermia is associated with
      bleeding and increased transfusion requirements in surgery patients. On the other
      hand, crystalloid hemodilution has been shown to induce a hypercoagulable state.
      The study aim was to elucidate in which way the induction of mild therapeutic
      hypothermia by a bolus infusion of cold crystalloids affects the coagulation
      system of patients with cardiac arrest. METHODS: This was a prospective pilot
      study in 18 patients with cardiac arrest and return of spontaneous circulation
      (ROSC). Mild hypothermia was initiated by a bolus infusion of cold 0.9% saline
      fluid (4 degrees C; 30ml/kg/30min) and maintained for 24h. At 0h (before
      hypothermia), 1, 6 and 24h we assessed coagulation parameters (PT, APPT),
      platelet count and performed thrombelastography (ROTEM) after in vitro addition
      of heparinase. RESULTS: A total amount of 2528 (+/-528)ml of 0.9% saline fluid
      was given. Hematocrit (p<0.01) and platelet count (-27%; p<0.05) declined,
      whereas APTT increased (2.7-fold; p<0.01) during the observation period. All
      ROTEM parameters besides clotting time (CT) after 1h (-20%; p<0.05) did not
      significantly change. CONCLUSION: Mild hypothermia only slightly prolonged
      clotting time as measured by rotation thrombelastography. Therefore, therapeutic
      hypothermia initiated by cold crystalloid fluids has only minor overall effects
      on coagulation in patients with cardiac arrest.

PMID- 19406553
TI  - Gunshot through the left ventricle.

PMID- 19406554
TI  - Erythropoietin improved initial resuscitation and increased survival after
      cardiac arrest in rats.
AB  - INTRODUCTION: Recent data have demonstrated potent cardioprotective and
      neuroprotective effects of the application of growth hormones like erythropoietin
      (EPO) after focal cardiac or cerebral ischemia. In order to assess possible
      benefits regarding survival and resuscitation conditions, EPO was tested against
      placebo in a model of cardiac arrest in the rat. METHODS: Thirty-four male Wistar
      rats were randomized into two groups (EPO versus control; n=17 per group). Under
      anesthesia, cardiac arrest was induced by asphyxia after neuromuscular blockade.
      After 6 min of global ischemia, animals were resuscitated by external chest
      compression combined with epinephrine administration. An intravenous bolus of
      recombinant human EPO (rhEPO, 3000 UIkg(-1) body weight, i.v.) or saline (in
      control group) was performed 15 min before cardiac arrest, by a blinded
      investigator. Restoration of spontaneous circulation (ROSC), survival at 1, 24,
      48 and 72 h and hemodynamic changes after cardiac arrest were studied. RESULTS:
      Survival to 72 h was significantly improved in the EPO group (n=15/17) compared
      to the control group (n=7/17). All the EPO-treated rats were successfully
      resuscitated whereas only 13 of 17 control animals resuscitated. EPO-treated
      animals required a significantly smaller dose of epinephrine before
      resuscitation, compared to control rats. Time course of systolic arterial blood
      pressure after resuscitation revealed no significant differences between both
      groups. CONCLUSION: EPO, when administrated before cardiac arrest, improved
      initial resuscitation and increased the duration of post-resuscitation survival.

PMID- 19406555
TI  - Prediction of clinical infection in women with preterm labour with intact
      membranes: a score based on ultrasonographic, clinical and biological markers.
AB  - OBJECTIVE: To predict maternal and neonatal clinical infection at admission in
      women hospitalized for preterm labour (PTL) with intact membranes. STUDY DESIGN:
      Prospective study of 371 women hospitalized for preterm labour with intact
      membranes. The primary outcome was clinical infection, defined by clinical
      chorioamnionitis at delivery or early-onset neonatal infection. RESULTS: Clinical
      infection was identified in 21 cases (5.7%) and was associated with earlier
      gestational age at admission for PTL, elevated maternal C-reactive protein (CRP)
      and white blood cell count (WBC), shorter cervical length, and a cervical
      funnelling on ultrasound. We used ROC curves to determine the cut-off values that
      minimized the number of false positives and false negatives. The cut-off points
      chosen were 30 weeks for gestational age at admission, 25 mm for cervical length,
      8 mg/l for CRP and 12,000 c/mm(3) for WBC. Each of these variables was assigned a
      weight on the basis of the adjusted odds ratios in a clinical infection risk
      score (CIRS). We set a threshold corresponding to a specificity close to 90%, and
      calculated the positive and negative predictive values and likelihood ratios of
      each marker and of the CIRS. The CIRS had a sensitivity of 61.9%, while the
      sensitivity of the other markers ranged from 19.0% to 42.9%. Internal cross
      validation was used to estimate the performance of the CIRS in new subjects. The
      diagnostic values found remained close to the initial values. CONCLUSION: A
      clinical infection risk score built from data known at admission for preterm
      labour helps to identify women and newborns at high risk of clinical infection.

PMID- 19406556
TI  - Unusual multiple gestation after ICSI/KET: a case report.

PMID- 19406557
TI  - Iron prophylaxis in pregnancy: intravenous route versus oral route.
AB  - OBJECTIVE: To assess and compare the efficacy and safety of two and three doses
      of intravenous iron sucrose with daily oral ferrous sulphate in the prophylaxis
      of iron deficiency anaemia in pregnant women. STUDY DESIGN: 260 women with
      singleton pregnancy who met inclusion criteria and who gave informed consent were
      randomised between the 21st and 24th week into either the intravenous iron group
      or the oral iron group. Of 130 women in the intravenous iron group, 75 women
      received two doses of 200mg iron sucrose and 55 three doses of 200mg iron
      sucrose. The first dose was administered between the 21st and 24th gestational
      weeks, the second between the 28th and 32nd and the third between the 35th and
      37th. The women of the oral group were given oral tablets of 80 mg ferrous
      sulphate daily, beginning on the day of study enrolment and stopping on the day
      of delivery. RESULTS: There was a non-significant trend to a higher frequency of
      responders (haemoglobin> or =11 g/dl) in the intravenous iron group (75 vs. 80%).
      There was a significant difference of repleted iron stores before delivery
      (ferritin>50 microg/l) in the group with three intravenous iron doses in
      comparison to the oral iron group (49 vs. 14%; p<0.001). No differences were
      observed in regard to maternal and perinatal outcomes. CONCLUSIONS: There was no
      clinically significant difference in the haematological, maternal and foetal
      outcomes in the parenteral route of iron prophylaxis in pregnant women.

PMID- 19406558
TI  - Thyroid volume changes during pregnancy and after delivery in an iodine
      sufficient Republic of Slovenia.
AB  - OBJECTIVE: Literature data concerning thyroid enlargement during pregnancy are
      not conclusive. Our aim was to systematically follow the thyroid volume changes
      during pregnancy and after delivery in an iodine-sufficient area. STUDY DESIGN:
      Prospective study of healthy pregnant women living in an iodine-sufficient area.
      We followed 118 pregnant women with the mean age 30.9+/-4.1 years in the first
      trimester (mean 11.2+/-2.5 weeks of pregnancy), in the third trimester (mean
      31.6+/-1.7 weeks of pregnancy), and 4 months after delivery (mean 15.9+/-3.9
      weeks). Additionally, 71 women were also evaluated 14 months after delivery (mean
      13.3+/-1.1 months). All women were negative for thyroid autoantibodies. We
      measured urinary iodine concentration (UIC), thyroid volume, serum TSH, and body
      mass index (BMI). After delivery, in a subgroup of women we also estimated the
      colour flow Doppler sonography (CFDS) patterns 0, I, II and III, where thyroid
      vascularity increased from pattern 0 to III, and the peak systolic velocity (PSV)
      using a 7.5 mHz linear transducer. RESULTS: Median UIC in the third trimester
      (176 microg/g creatinine) was significantly higher than 4 and 14 months after
      delivery (P=0.030, P<0.001, respectively). Thyroid volume in the third trimester
      (11.3+/-3.1 mL) was significantly greater (P<0.001) than in the first trimester
      (8.7+/-2.5 mL), 4 months after delivery (8.6+/-2.5) and 14 months after delivery
      (7.8+/-2.4 mL). TSH concentration was significantly higher in the third trimester
      than in the first trimester and 4 months after delivery (P=0.007, P=0.006,
      respectively). As expected, BMI was the highest in the third trimester. CFDS
      pattern I was more frequent 4 months after delivery than 14 months after delivery
      (P<0.001). Similarly, PSV was significantly higher 4 months after delivery than
      14 months after delivery (P<0.001). Linear regression analysis revealed TSH and
      BMI as significant independent predictors for thyroid volume. CONCLUSION: In an
      iodine-sufficient area, thyroid volume increases during pregnancy and decreases
      after delivery, and the changes in volume are associated with changes in TSH and
      BMI. They may be viewed as indicators for metabolic and haemodynamic changes
      during pregnancy.

PMID- 19406559
TI  - Clitoral metastasis of anal adenocarcinoma associated with rectovaginal fistula
      in long standing Crohn's disease.

PMID- 19406560
TI  - Environmental impact and management of phosphogypsum.
AB  - The production of phosphoric acid from natural phosphate rock by the wet process
      gives rise to an industrial by-product called phosphogypsum (PG). About 5 tons of
      PG are generated per ton of phosphoric acid production, and worldwide PG
      generation is estimated to be around 100-280 Mt per year. This by-product is
      mostly disposed of without any treatment, usually by dumping in large stockpiles.
      These are generally located in coastal areas close to phosphoric acid plants,
      where they occupy large land areas and cause serious environmental damage. PG is
      mainly composed of gypsum but also contains a high level of impurities such as
      phosphates, fluorides and sulphates, naturally occurring radionuclides, heavy
      metals, and other trace elements. All of this adds up to a negative environmental
      impact and many restrictions on PG applications. Up to 15% of world PG production
      is used to make building materials, as a soil amendment and as a set controller
      in the manufacture of Portland cement; uses that have been banned in most
      countries. The USEPA has classified PG as a "Technologically Enhanced Naturally
      Occurring Radioactive Material" (TENORM). This work reviews the different
      environmental impacts associated with PG storage and disposal. The methods
      described in the literature to minimise the negative effects of this waste are
      classified by treatment type, i.e. physical, chemical, thermal, etc., and
      different suggested applications for PG are detailed.

PMID- 19406561
TI  - Removal of organic pollutants and nutrients from olive mill wastewater by a sand
      filter.
AB  - The aim of this work was to examine the performance of a sand filter in treating
      modern olive mill (OMW) effluents after dilution with domestic wastewater on a
      one-to-one basis. The experimental pilot consisted of a column of opaque PVC, and
      the sand filter was filled with 50 cm of sand and 10 cm of gravel in the top and
      the bottom of the filter. The alimentation (4 cm/day) was done sequentially
      following a 1 day wet/3 days dry cycle. The OMW effluent was very acidic with a
      pH of 4.12, and had high concentrations of phenolic compounds (7.2g/L) and total
      chemical oxygen demand (65 g/L). The percolation of the diluted OMW through the
      sand filters caused an increase in pH from 4.84 to 8.25 and a 90% removal of
      total suspended solids. The sand filter treatment also led to important
      reductions in organic matter (90% of total COD, 83% of dissolved COD and 92% of
      phenolic compounds) and nutrients (91% of Kjeldahl-nitrogen, 97% of ammonia
      nitrogen, 99% of nitrate-nitrogen and 99% of phosphates). The flow rate became
      very low indicating clogging of the sand pores after 10 weeks. HPLC analysis of
      the diluted OMW before and after passage through the sand filter showed an
      important reduction in the toxic monomeric compounds after the treatment.

PMID- 19406562
TI  - Factors predicting health-related quality of life recovery in patients undergoing
      surgical treatment for renal tumors: prospective evaluation using the RAND SF-36
      Health Survey.
AB  - BACKGROUND: Most newly diagnosed kidney cancers present at localized stages. With
      appropriate treatments, the cancer-specific survival rates of such patients are
      extremely high, which makes patients' health-related quality of life (HRQoL) a
      relevant issue. To date, most of the available studies on HRQoL have been biased
      by the absence of baseline HRQoL assessments and by retrospective designs.
      OBJECTIVE: To evaluate the baseline HRQoL of patients with kidney cancer,
      comparative HRQoL during the first year after surgery, and the prognostic factors
      predictive of HRQoL recovery. DESIGN, SETTING, AND PARTICIPANTS: We prospectively
      collected the data of all patients undergoing surgery for kidney tumors at a
      tertiary academic referral center from February 2006 to September 2007.
      INTERVENTIONS: Patients underwent nephron-sparing surgery (NSS) or radical
      nephrectomy (RN). MEASUREMENTS: Patients were invited to self-complete the
      validated, Italian version of the RAND 36-Item Health Survey 1.0 (SF-36) before
      surgery, 6 mo after surgery, and 12 mo after surgery. RESULTS AND LIMITATIONS:
      Overall, 129 consecutive patients were evaluated. No significant differences were
      found between the baseline scores of our patients and age- and sex-matched
      normative data for the Italian general population. Comparing the baseline SF-36
      scores to those at 6 mo and 12 mo, there was statistically significant worsening
      in the physical domains and improvement in the emotional domains (all p<0.05).
      About 50-80% of patients returned to baseline scores 6 mo and 12 mo after
      surgery. Age, body mass index (BMI), educational level, occupational status, New
      York Heart Association (NYHA) functional class, tumor mode of presentation,
      pathologic stage, size, and histologic subtype were associated with 6-mo and 12
      mo return to the baseline HRQoL scores. The main limitation of the study was the
      lack of a disease-specific questionnaire. CONCLUSIONS: Most patients returned to
      preoperative HRQoL within 12 mo after RN or NSS. Several patient features,
      clinical variables, and pathologic tumor variables predict the return of HRQoL.

PMID- 19406563
TI  - NOTES hybrid transvaginal radical nephrectomy for tumor: stepwise progression
      toward a first successful clinical case.
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) has been used
      to perform nephrectomy in the laboratory; however, clinical reports to date have
      used multiple abdominal trocars to assist the transvaginal procedure. OBJECTIVE:
      To present our stepwise technique development and the first successful clinical
      case of NOTES transvaginal radical nephrectomy for tumor with umbilical
      assistance without extraumbilical skin incisions. DESIGN, SETTING, AND
      PARTICIPANTS: The four transvaginal NOTES procedures were performed at two
      institutions after obtaining institutional review board approval. Various
      operative steps were developed experimentally in three clinical cases, and on
      March 7, 2009, we performed the first successful case of NOTES hybrid
      transvaginal radical nephrectomy without any extraumbilical skin incisions. Using
      one multichannel access port in the vagina and one in the umbilicus, laparoscopic
      visualization, intraoperative tissue dissection, and hilar control were performed
      transvaginally and transumbilically. The intact specimen was extracted
      transvaginally. MEASUREMENTS: All perioperative data were accrued prospectively.
      A stepwise progression to the successful completion of the fourth case is
      systematically presented. RESULTS AND LIMITATIONS: Intraoperatively, at
      incrementally more advanced stages of the procedure, the first three NOTES
      clinical cases were electively converted to standard laparoscopy because of
      rectal injury during vaginal entry, of failure to progress, and of gradual
      bleeding during upper-pole dissection after transvaginal hilar control,
      respectively. The fourth case was successfully completed via transvaginal and
      umbilical access without conversion to standard laparoscopy. Operative time was
      3.7 h, estimated blood loss was 150 cm(3), and hospital stay was 1 d. Final
      pathology confirmed a 220-g, pT1b, 7-cm, grade 2, clear-cell renal cell carcinoma
      with negative margins. The patient was readmitted for an intraabdominal
      collection that responded to drainage and antibiotics. CONCLUSIONS: We report our
      stepwise progression and the initial successful clinical case of NOTES hybrid
      transvaginal radical nephrectomy for tumor, assisted with only one umbilical
      trocar. Although transvaginal nephrectomy is feasible in the highly selected
      patient with favorable intraoperative circumstances, considerable refinements in
      technique and technology are necessary if this approach is to advance beyond mere
      anecdote.

PMID- 19406564
TI  - Editorial comment on: Factors predicting health-related quality of life recovery
      in patients undergoing surgical treatment for renal tumors: prospective
      evaluation using the RAND SF-36 Health Survey.

PMID- 19406565
TI  - Lower urinary tract symptoms revisited.

PMID- 19406566
TI  - Editorial comment on: Factors predicting health-related quality of life recovery
      in patients undergoing surgical treatment for renal tumors: prospective
      evaluation using the RAND SF-36 Health Survey.

PMID- 19406568
TI  - Studies on the biosorption of hexavalent chromium from aqueous solutions by using
      boiled mucilaginous seeds of Ocimum americanum.
AB  - Investigations were carried out to study the chromium removal efficiency of
      boiled mucilaginous seeds of Ocimum americanum. Batch experiments were conducted
      to study the biosorption kinetics of chromium removal for the concentrations
      10mg/L, 20mg/L and 40 mg/L of chromium(VI) solutions. The biosorbent dosage was 8
      g dry seeds/L. The toxic hexavalent chromium was reduced to less toxic
      chromium(III) in the presence of seeds and the reduced chromium was adsorbed on
      the mucilage of seeds. Both the chromium(VI) and chromium(III) were present in
      the aqueous phase. The optimum chromium reduction and adsorption was observed at
      the pH value 1.5. The biosorption data fitted well with Langmuir isotherm. The
      biosorption capacity calculated from the Langmuir isotherm was q=32 mg
      chromium(III)/g of dry seeds. The continuous column study was also carried out at
      the flow rate of 27 mL/h for the initial concentration 25mg/L of chromium(VI)
      feed solution using a packed bed column filled with boiled mucilaginous seeds.
      The maximum reduction of chromium(VI) to chromium(III) in the packed bed was 80%.
      The percentage removal of reduced chromium from the aqueous solution was 56.25%.
      This value was maintained constant until 0.52 L of chromium(VI) solution was
      pumped through the packed bed column. Thus the naturally immobilized
      polysaccharides on the seeds mimic the microbial polysaccharides in terms of
      their ability to adsorb heavy metals with an added advantage of making the
      immobilization step unnecessary which is a major cost factor of the metal removal
      process when microbial exopolysaccharides used. The uniform size and spherical
      shape of swollen seeds give an additional advantage to use them in a packed bed
      column for continuous removal of chromium(VI) from aqueous solutions.

PMID- 19406569
TI  - Evaluation of chelating ion-exchange resins for separating Cr(III) from
      industrial effluents.
AB  - In this study two chelating resins containing iminodiacetic acid groups
      (Amberlite IRC 748 and Diaion CR 11) and a chelating resin based on sulfonic and
      diphosphonic acid groups (Diphonix) were investigated in order to separate
      Cr(III) from industrial effluents produced in hard and decorative electroplating.
      Samples of two industrial plants were characterized during a period of about one
      year and a half in terms of the metals content (Cr, Cu, Na, Ca, Fe and Ni), Total
      Suspended Solids (TSS), Total Dissolved Solids (TDS), Chemical Oxygen Demand
      (COD) and pH. Some of the physical properties of the resins, namely the moisture
      content, apparent density, intraparticle porosity and the particle size
      distribution were also evaluated. To quantify the sorption capacity of the
      resins, batch experiments were performed using synthetic solutions of Cr(III), as
      well as solutions of Fe in the case of Diphonix. The Langmuir and Langmuir
      Freundlich isotherms enabled a good description of the ion-exchange equilibrium
      data, and the maximum sorption capacity determined for Amberlite and Diaion was
      3.6 mequiv./g(dry resin). For Diphonix that parameter was 3.4 mequiv./g(dry
      resin). The Diphonix resin exhibits a high selectivity for transition metals (Fe,
      Ni) over the chromium trivalent. Therefore, it was screened as the most suitable
      for selectively removing those metal impurities from chromium electroplating
      effluents. For this resin, the sorption capacity is strongly dependent on the
      initial pH of the solution. Though, high regeneration efficiencies of Diphonix
      for stripping Cr(III) were found by using a mixture of NaOH/H(2)O(2). The
      mathematical model tested for describing the dynamics of the process allowed a
      good fitting to the experimental data and enabled the estimation of effective
      pore diffusivity of Cr(III). The saturations of Diphonix with industrial
      effluents demonstrated that the breakthrough capacity of the resin is affected by
      the presence of other species in solution, such as Fe and Ni. Nevertheless, these
      effluents may be treated with this resin, being possible to separate Cr(III) from
      other transition metallic ions in solution.

PMID- 19406570
TI  - Simultaneous methanogenesis and denitrification of aniline wastewater by using
      anaerobic-aerobic biofilm system with recirculation.
AB  - Wastewater containing highly concentrated nitrogenous and aromatic compounds,
      such as aniline, is difficult to degrade and very toxic to microorganisms,
      especially to nitrifier. In order to remove both carbon and nitrogen from aniline
      wastewater, recently two biofilm reactors equipped with anaerobic-aerobic cycle
      and internal recirculation have demonstrated some potential in treating the
      wastewater. In such system, ammonification, methanogenesis and denitrification
      reactions occurred simultaneously in one anaerobic reactor, followed by COD
      removal and nitrification in the aerobic reactor. The effect of recirculation
      ratio on COD and nitrogen removal using such reactor arrangement was therefore
      investigated in the present work. The results showed that recirculation had
      little impact on the overall COD removal or denitrification activity in the
      anaerobic reactor at any tested ratio, 96-98% of overall COD removal efficiency
      was achieved with a final effluent COD value below 200mg/L. But nitrification and
      TN removal were strongly affected by recirculation. The nitrification rate
      reached a maximum of 0.48 kg N/(m(3)d) at recirculation ratio of 1 and complete
      nitrification was achieved at the recirculation ratios over 2. TN removal
      efficiency increased continuously and a sharp reduction of sludge production in
      the system was observed with increasing recirculation.

PMID- 19406571
TI  - Removal and recovery of acridine orange from solutions by use of magnetic
      nanoparticles.
AB  - Here we report a separation of a cationic dye, acridine orange (AO), by use of
      magnetic nanoparticles (gamma-Fe(2)O(3)). The particles were showed to capture
      98% of the dye within the first 20 min of contact time. The maximum sorption
      capacity of the magnetic nanoparticles (MNPs) for AO was 59mg/g. The sorption
      isotherms fit well with the Freundlich model. The sorption kinetics fits well the
      pseudo-second-order rate equation model. 60-90% dye recovery was achieved by
      rotary evaporating the dye bearing nanoparticles in acetone. The nanoparticles
      were recycled for additional dye removal.

PMID- 19406572
TI  - Stabilisation of Cr(VI) in stainless steel plant dust through sintering using
      silica-rich clay.
AB  - Stainless steel plant dust is considered a hazardous waste due to the fact that
      it contains significant levels of Cr(VI) and other heavy metals such as lead and
      zinc. It should therefore be treated before being stockpiled or land filled.
      Solidification/stabilisation processes are effective techniques for the
      immobilisation of heavy metals. This paper consequently describes an
      investigation into the stabilisation of Cr(VI) in stainless steel plant dust with
      silica-rich clay in a sintering process. The results indicate that Cr(VI) in the
      stainless steel dust can be stabilised in a 50 mass% dust:50 mass% clay mixture
      at an optimum sintering temperature of 1100 degrees C, and minimum sintering time
      of 5h. Chromium emission during the sintering process was found to be low, and
      within environmental limits.

PMID- 19406573
TI  - Synthesis of a novel chelating resin and its use for selective separation and
      preconcentration of some trace metals in water samples.
AB  - A new chelating resin, poly[N-(4-bromophenyl)-2-methacrylamide-co-2-acrylamido-2
      methyl-1-propanesulfonic acid-co-divinylbenzene], was synthesized and
      characterized. The resin was used for selective separation, preconcentration and
      determination of Cu(II), Ni(II), Co(II), Cd(II), Pb(II), Mn(II) and Fe(III) ions
      in water samples by flame atomic absorption spectrometry. Effects of pH,
      concentration and volume of elution solution, sample flow rate, sample volume and
      interfering ions (Na(+), K(+), Ca(2+), Mg(2+), Fe(3+), Mn(2+), Al(3+), Zn(2+),
      Pb(2+), Cu(2+), Ni(2+), Cd(2+), Cl(-) and SO(4)(2-)) on the recovery of the
      analytes were investigated. The sorption capacity of the resin was 25.6, 19.8,
      32.1, 41.3, 38.9, 13.9 and 18.3 mg g(-1) for Cu(II), Ni(II), Co(II), Cd(II),
      Pb(II), Mn(II) and Fe(III), respectively. A high preconcentration factor, 100,
      and low relative standard deviation, <or=2.5% (n=7) values were obtained. The
      detection limits (microg L(-1)) were 0.57 for Cu(II), 0.37 for Ni(II), 0.24 for
      Co(II), 0.09 for Cd(II), 1.6 for Pb(II), 0.19 for Mn(II) and 0.72 for Fe(III).
      The method was validated by analysing fortified lake water (TMDA-54.4, a trace
      element fortified calibration standard) and spiked water samples. The method was
      applied to the determination of the analytes in tap and lake water samples.

PMID- 19406574
TI  - Nitrate sorption by thermally activated Mg/Al chloride hydrotalcite-like
      compound.
AB  - A laboratory study was conducted to investigate the ability of Mg-Al-Cl
      hydrotalcite-like compound for the removal of nitrate from synthetic nitrate
      solution. In the present study Mg-Al-Cl hydrotalcite was synthesized by co
      precipitation method and was characterized using SEM, XRD, FTIR and TGA-DSC. To
      know the practical applicability, a detailed removal study of nitrate ion was
      carried out. The removal of nitrate was 87.6% under neutral condition, using 0.3g
      of adsorbent in 100mL of nitrate solution having initial concentration of 10mg/L.
      Adsorption kinetic study revealed that the adsorption process followed first
      order kinetics. Adsorption data were fitted to linearly transformed Langmuir
      isotherm with R(2) (correlation coefficient)>0.99. Thermodynamic parameters were
      also calculated to study the effect of temperature on the removal process. In
      order to understand the adsorption type, equilibrium data were tested with
      Dubinin-Radushkevich isotherm. The percentage removal was found to decrease
      gradually with increase in pH and the optimum pH was found to be 6. The process
      was rapid and equilibrium was established within first 40 min.

PMID- 19406575
TI  - Photo-degradation of acid red 44 using Al and Fe modified silicates.
AB  - Al and Fe modified silicates were synthesized using the hydrothermal method. The
      obtained materials were calcined at different temperatures (250, 500 and 750
      degrees C) and characterized using XRD, FTIR, UV and SEM spectroscopy. The
      obtained materials were applied for the photo-decolorization of acid red 44 as a
      member of azo dye family, in aqueous medium using UV irradiation (lambda=254 nm)
      under different experimental conditions. The effect of calcination temperature,
      catalyst concentration and pH on the decolorization of acid red 44 dye were
      investigated. The decolorization of acid red 44 dye and the decreasing in
      concentration of the formed intermediates have been followed using UV-vis
      spectrophotometry and high performance liquid chromatography (HPLC). Results
      showed that the addition of Al and Fe-silicate to the dye solution as well as pH
      change greatly enhanced the rate of degradation. The decolorization followed the
      pseudo first order kinetics model and a significant mineralization of AR44 was
      observed.

PMID- 19406576
TI  - A randomized trial of a tailored barriers intervention for Cancer Information
      Service (CIS) callers in pain.
AB  - Cancer pain management can be improved by overcoming patients' attitudinal
      barriers to reporting pain and using analgesics. A simple cost-effective barriers
      intervention designed to reach a large number of persons with cancer has not yet
      been tested. Such an intervention should be tested against barriers' assessment
      alone, as well as no-treatment control. The purpose of this study was to test the
      efficacy and the cost effectiveness of a tailored barriers intervention (TBI), an
      educational intervention tailored to participants' attitudinal barriers toward
      reporting pain and using analgesics. This was a randomized three-group (TBI,
      assessment-alone, or control) trial with measures at baseline and 28 days later
      conducted at the NorthCentral and Heartland offices of the Cancer Information
      Service (CIS), an NCI program that provides information to persons seeking
      answers to cancer-related questions. Participants (1256 adult CIS callers
      diagnosed with cancer with moderate to severe pain in the past week) joined the
      study and were randomized. Of these participants, 970 (77.23%) provided follow-up
      data. The TBI consisted of educational messages tailored to each participant's
      attitudinal barriers, delivered orally over the telephone, followed by a printed
      mailed copy. The outcome measures were attitudinal barriers to pain management,
      as well as pain outcomes (duration, severity, and interference with life
      activities). At follow-up the TBI group had significantly lower attitudinal
      barriers scores compared to assessment-alone and control, but the groups did not
      differ on the pain outcome variables. TBI and assessment-alone had similar cost
      effectiveness. The TBI needs to be strengthened to achieve reductions in pain
      severity.

PMID- 19406577
TI  - Molecular diagnosis of ascariasis from human feces and description of a new
      Ascaris sp. genotype in Brazil.
AB  - It is estimated that 120 million people are infected by Ascaris lumbricoides in
      Latin America, but few genomic studies have been conducted. We tested protocols
      for DNA extraction to obtain an Ascaris sp. molecular diagnosis from human feces,
      with the emphasis on PCR specificity and sensitivity. Ascaris sp. was detected in
      100% of positive fecal samples using physico-chemical DNA extraction and the cytb
      gene and ITS1 as molecular targets. The method was sufficiently sensitive to
      detect Ascaris sp. from one isolated egg or four eggs in a fecal sample.
      Regarding the PCR specificity, there was no cross-reactivity when applied to
      Trichuris trichiura-positive fecal samples or in Ascaris sp. samples also
      positive to T. trichiura or Enterobius vermicularis. The ITS1 sequence analysis
      revealed two genotypes among the sample: the G1 genotype, the most prevalent in
      humans, and a new genotype, G6, described for the first time in Brazilian
      samples.

PMID- 19406578
TI  - Spirurids from Gracilinanus agilis (Marsupialia: Didelphidae) in Brazilian
      Pantanal wetlands with a new species of Physaloptera (Nematoda: Spirurida).
AB  - Gastrointestinal nematodes were recovered from thirty four Gracilinanus agilis
      from forty four collected in Pantanal, Mato Grosso do Sul State, Brazil. Two
      hundred seventy four spirurids were recovered from the esophagus, stomach and
      intestines, comprising three species from three different genera. These were
      identified as Pterygodermatites (Paucipectines) jagerskioldi, Spirura guianensis
      and Physaloptera herthameyerae n. sp. is first described. This is the first
      record of nematodes of the genera Physaloptera and Spirura in hosts of the genus
      Gracilinanus. The high prevalence of spirurids in 72.3% of the G. agilis
      collected probably is influenced by the arboreal and diet behaviors.

PMID- 19406579
TI  - A Th2 type of immune response is associated with increased resistance to
      Haemonchus contortus in naturally infected Gulf Coast Native lambs.
AB  - Haemonchus contortus is one of the major nematode parasites causing substantial
      economic losses in small ruminant farming worldwide. Recently, effectiveness of
      anthelmintic treatment has decreased due to an increasing problem of nematode
      populations that have developed resistance to anthelmintics. Efforts to develop
      effective vaccines have had limited success. There are certain breeds of sheep
      that are relatively resistant to the parasite including Gulf Coast Native
      (Native) sheep. Understanding the protective nature of the immune response that
      helps these breeds of sheep control infection could enable the development of
      vaccines to enhance control programs. This experiment was designed to compare the
      immunological responses of resistant Native versus susceptible Suffolk sheep in
      order to identify the mechanisms responsible for this resistance. Immune
      responses were evaluated in naturally infected Native and Suffolk lambs that
      grazed pasture contaminated predominantly with H. contortus. Ten lambs of each
      breed grazed together for 42 days. Fecal, blood and serum samples were collected
      on 0, 2, 4, 7, 10, 14, 21, 28, 35 and 42 days of exposure. Five lambs of each
      breed were necropsied on day 35 and five on day 42 for nematode recovery and
      abomasal tissue sample collection. Throughout the course of infection, Native
      lambs had significantly lower FEC, significantly lower PCV reduction percent, and
      significantly higher serum IgE after day 14 and increased expression of IL-4 on
      day 10 post-exposure compared to Suffolk lambs. At both necropsy time points,
      Native lambs had significantly greater numbers of mucosal mast cells, eosinophils
      and globule leukocytes in abomasal mucosa than Suffolk lambs. Results indicated
      that Native lambs had a more pronounced immune response to infection with H.
      contortus than Suffolk lambs which may be responsible for the observed resistance
      to infection.

PMID- 19406580
TI  - Diurnal pattern of cortisol output in postnatal depression.
AB  - This study investigated the diurnal output of saliva cortisol in women with
      symptoms of depression postnatally. Twenty-one depressed and 30 non-depressed
      women at 7.5 weeks postpartum, and 21 non-perinatal controls, collected saliva at
      waking, 30 min, and 3 and 12h postwaking. Women who were not depressed
      postnatally showed a pattern of cortisol secretion over the day similar to non
      perinatal controls. There was a significant difference in diurnal pattern between
      postnatally depressed and postnatally non-depressed women, due to a difference in
      the first two time points (waking and +30 min): compared to the other two groups
      who each had a significant increase in cortisol levels from waking to +30 min,
      the depressed women had significantly higher cortisol levels at waking and no
      increase at +30 min. The lack of a morning rise in the depressed women is similar
      to that reported for posttraumatic stress disorder and chronic fatigue syndrome
      and may reflect a response, in vulnerable women, to the marked cortisol
      withdrawal that occurs after delivery.

PMID- 19406581
TI  - Hypothalamic-pituitary-adrenal axis dysregulation in depressed children and
      adolescents: a meta-analysis.
AB  - Research findings on the hypothalamic-pituitary-adrenal (HPA) axis and pediatric
      depression reflect a variety of methodological approaches that tap different
      facets of HPA-axis functions. Partly owing to the methodological heterogeneity of
      studies, descriptive reviews of this area have produced inconsistent conclusions.
      Therefore, we conducted formal meta-analyses of pertinent studies in order to
      advance our understanding of HPA-axis dysregulation in pediatric depression. We
      examined: (a) 17 published studies of HPA-axis response to the dexamethasone
      suppression test (DST) in depressed youth (DST; N=926) and (b) 17 studies of
      basal HPA-axis functioning (N=1332). We also examined descriptively studies that
      used corticotropin-releasing hormone (CRH) infusion, and those that used
      psychological probes of the HPA-axis. The global standardized mean effect size
      difference in HPA-axis response to the DST between depressed and non-depressed
      youth was 0.57, z=4.18, p<0.01. The global standardized mean difference effect
      size in basal HPA-axis functioning was 0.20, z=4.53, p<0.01. Age, sex, timing of
      sampling, dexamethasone dosage, or type of control group was not a significant
      source of variability for the DST or basal studies. In addition, when compared to
      non-depressed peers, depressed youth have a normative response to CRH infusion
      but an overactive response to psychological stressors. In conclusion, the HPA
      axis system tends to be dysregulated in depressed youth, as evidenced by atypical
      responses to the DST, higher baseline cortisol values, and an overactive response
      to psychological stressors. This pattern of dysregulation suggests anomalies
      within the axis's negative feedback system and CRH production, but intact
      pituitary and adrenal sensitivity.

PMID- 19406583
TI  - A Quick Drinking Screen for identifying women at risk for an alcohol-exposed
      pregnancy.
AB  - Two previous studies comparing the Quick Drinking Screen (QDS) with the Timeline
      Followback (TLFB) found that these two instruments yielded similar reports of
      alcohol use for clinical and nonclinical populations of problem drinkers. The
      current study evaluated the correspondence between these two drinking measures
      with women at risk of an Alcohol-Exposed Pregnancy (AEP). Participants were 355
      women who voluntarily participated in a research study during 2005 through 2007
      designed to prevent AEPs. All women were screened by phone for eligibility using
      the QDS and approximately 2 weeks later completed a 3-month TLFB by mail. Results
      of this study, analyzed in 2008, paralleled previous studies showing that the QDS
      and the TLFB, two very different drinking measures, collected similar aggregate
      drinking data for women who drink heavily and are at risk of an AEP.
      Correspondence between the two drinking measures met acceptable levels of
      reliability. The present study found that the QDS has demonstrated efficacy for
      screening women whose level of alcohol use puts them at risk for an AEP. Although
      the QDS does not yield detailed drinking information, it could be used when it is
      not possible or necessary to gather daily drinking data.

PMID- 19406584
TI  - The gluten syndrome: a neurological disease.
AB  - HYPOTHESIS: Gluten causes symptoms, in both celiac disease and non-celiac gluten
      sensitivity, by its adverse actions on the nervous system. Many celiac patients
      experience neurological symptoms, frequently associated with malfunction of the
      autonomic nervous system. These neurological symptoms can present in celiac
      patients who are well nourished. The crucial point, however, is that gluten
      sensitivity can also be associated with neurological symptoms in patients who do
      not have any mucosal gut damage (that is, without celiac disease). Gluten can
      cause neurological harm through a combination of cross reacting antibodies,
      immune complex disease and direct toxicity. These nervous system affects include:
      dysregulation of the autonomic nervous system, cerebella ataxia, hypotonia,
      developmental delay, learning disorders, depression, migraine, and headache. If
      gluten is the putative harmful agent, then there is no requirement to invoke gut
      damage and nutritional deficiency to explain the myriad of the symptoms
      experienced by sufferers of celiac disease and gluten-sensitivity. This is called
      "The Gluten Syndrome".

PMID- 19406582
TI  - The prognostic power of normative influences among NCAA student-athletes.
AB  - This study evaluated the predictive power of perceived descriptive and injunctive
      norms on intercollegiate student-athlete alcohol consumption and attitudes toward
      drinking-related behaviors. The sample consisted of 594 NCAA student-athletes
      from two geographically opposite sites. Norms variables utilized a school and
      gender-specific athletic peer reference group. Results indicate that respondents
      reported greater perceived injunctive norms than actual attitudes, and greater
      perceived descriptive norms than actual alcohol use. Further, after accounting
      for demographics and alcohol motivations, perceived injunctive norms were the
      strongest predictors of athletes' attitudes with the final model explaining 54%
      of the variance. Similarly, perceived descriptive norms were among the strongest
      predictors of alcohol use with the final model explaining 69% of the variance.
      Future research may want to use both of these perceived norms constructs to
      create a more salient and targeted social norms intervention aimed at reducing
      risky behavior and permissive alcohol-related attitudes among this population.
      Utilizing this strong peer reference group as well as targeting both injunctive
      and descriptive norms may increase the power and saturation of prevention and
      intervention strategies.

PMID- 19406585
TI  - Visual outcome and tumor control after conformal radiotherapy for patients with
      optic nerve sheath meningioma.
AB  - PURPOSE: Optic nerve sheath meningioma (ONSM) is a rare tumor that almost
      uniformly leads to visual dysfunction and even blindness without intervention.
      Because surgical extirpation carries a high risk of postoperative blindness,
      vision-sparing treatment strategies are desirable. METHODS AND MATERIALS: We
      retrospectively reviewed the outcomes of 25 patients (25 optic nerves) with ONSM,
      treated at a single institution with conformal fractionated radiotherapy by
      either stereotactic photon or proton radiation. Primary endpoints were local
      control and visual acuity. RESULTS: The patients presented with symptoms of
      visual loss (21) or orbital pain (3) or were incidentally diagnosed by imaging
      (3). The mean age was 44 years, and 64% were female patients. The indication for
      treatment was the development or progression of symptoms. Of the patients, 13
      were treated with photons, 9 were treated with protons, and 3 received a
      combination of photons and protons. The median dose delivered was 50.4 gray
      equivalents (range, 45-59.4 gray equivalents). Median follow-up after
      radiotherapy was 30 months (range, 3-168 months), with 3 patients lost to follow
      up. At most recent follow-up, 21 of 22 patients (95%) had improved (14) or stable
      (7) visual acuity. One patient had worsened visual acuity after initial
      postirradiation improvement. Of the 22 patients, 20 (95%) had no radiographic
      progression. Three patients had evidence of asymptomatic, limited retinopathy on
      ophthalmologic examination, and one had recurrent ONSM 11 years after treatment.
      CONCLUSIONS: Highly conformal, fractionated radiation therapy for symptomatic
      primary ONSM provides tumor control and improvement in visual function in most
      cases, with minimal treatment-induced morbidity. Longer follow-up is needed to
      assess the durability of tumor control and treatment-related late effects.

PMID- 19406586
TI  - Impact factors for microinvasion in patients with hepatocellular carcinoma:
      possible application to the definition of clinical tumor volume.
AB  - PURPOSE: To evaluate the degree of invasion of hepatocellular carcinoma (HCC)
      microscopically that will provide a potential application for gross tumor volume
      to clinical tumor volume (GTV-to-CTV) expansion. METHODS AND MATERIALS: From
      January 2002 to January 2006, 149 HCC patients were selected from those who had
      undergone surgical resection. Pathology slides and clinical data of all patients
      were reviewed, including platelet counts, serum alpha-fetoprotein (AFP) levels,
      degree of liver cirrhosis, tumor size, capsular status, portal vein invasion, TNM
      stage, and histologic tumor grade. The distance between the tumor margin (or
      fibrous capsule) and the invasive lesions was measured by senior pathologists.
      RESULTS: Of these 149 patients, 79 (53.0%) patients presented with tumor
      microinvasion between 0.5 and 4 mm. This degree of microinvasion was inversely
      correlated with lower platelet counts and positively correlated with higher AFP
      levels, larger tumor sizes, portal vein invasion, and advanced TNM stage.
      Microinvasion distances less than or equal to 2 mm were found in 96.1% of
      patients (74/77) with tumor dimensions less than or equal to 5 cm and in 94.5% of
      patients (85/90) with AFP levels less than 400 microg/l. CONCLUSIONS: Based on
      our study findings, GTV-to-CTV expansions of 4 mm for HCC are required to conceal
      the gross tumor and any microscopic disease with 100% accuracy. Tumor size and
      AFP levels are the simplest indicators for determining the GTV-to-CTV distance
      for HCC.

PMID- 19406587
TI  - Radiation therapy alone for imaging-defined meningiomas.
AB  - PURPOSE: To assess local control and treatment-related toxicity of single
      modality radiation therapy (RT) in the treatment of imaging-defined meningiomas.
      METHODS AND MATERIALS: The records of Emory University School of Medicine,
      Atlanta, GA, were reviewed between 1985 and 2003. We identified 41 patients with
      42 meningiomas treated with RT alone for lesions diagnosed on imaging alone. No
      patients received a histologic diagnosis. Patients in whom there was uniform
      agreement that the tumor represented a meningioma were accepted for therapy. Of
      the patients, 22 were treated with stereotactic radiosurgery (SRS), 11 with
      fractionated stereotactic radiotherapy (FSR), and 9 with three-dimensional
      conformal therapy (3DCRT). The median doses of SRS, FSR, and 3DCRT were 14 Gy,
      50.4 Gy, and 52.2 Gy, respectively. RESULTS: Median follow-up was 60 months. Of
      42 meningiomas, 39 were locally controlled. The 8-year actuarial local control
      rate by Kaplan-Meier methods was 94%. One failure occurred 6 months after 3DCRT,
      a second at 34 months after FSR, and a third at 125 months after SRS. A temporary
      symptomatic radiation-related neurologic sequela developed in 1 patient treated
      with SRS. No fatal treatment complications occurred. The 8-year rate for
      actuarial freedom from complication survival by Kaplan-Meier methods was 97%.
      CONCLUSIONS: RT alone is an attractive alternative to surgery for imaging-defined
      meningiomas without significant mass effect. It offers local control comparable
      to surgical resection with minimal morbidity. RT should be considered as a viable
      alternative to surgery for tumors in various locations.

PMID- 19406588
TI  - Regional lung density changes after radiation therapy for tumors in and around
      thorax.
AB  - PURPOSE: To study the temporal nature of regional lung density changes and to
      assess whether the dose-dependent nature of these changes is associated with
      patient- and treatment-associated factors. METHODS AND MATERIALS: Between 1991
      and 2004, 118 patients with interpretable pre- and post-radiation therapy (RT)
      chest computed tomography (CT) scans were evaluated. Changes in regional lung
      density were related to regional dose to define a dose-response curve (DRC) for
      RT-induced lung injury using three-dimensional planning tools and image fusion.
      Multiple post-RT follow-up CT scans were evaluated by fitting linear-quadratic
      models of density changes on dose with time as the covariate. Various patient-
      and treatment-related factors were examined as well. RESULTS: There was a dose
      dependent increase in regional lung density at nearly all post-RT follow-up
      intervals. The population volume-weighted changes evolved over the initial 6
      month period after RT and reached a plateau thereafter (p < 0.001). On univariate
      analysis, patient age greater than 65 years (p = 0.003) and/or the use of pre-RT
      surgery (p < 0.001) were associated with significantly greater changes in CT
      density at both 6 and 12 months after RT, but the magnitude of this effect was
      modest. CONCLUSIONS: There appears to be a temporal nature for the dose-dependent
      increases in lung density. Nondosimetric clinical factors tend to have no, or a
      modest, impact on these changes.

PMID- 19406589
TI  - Is social interaction associated with alcohol consumption in Uganda?
AB  - Little is documented about the association of alcohol consumption and social
      interaction in Uganda, a country with one of the highest per capita alcohol
      consumptions in the world. This paper describes the pattern of social interaction
      by sex and establishes the relationship between social interaction and alcohol
      consumption with and without the consideration of confounders. The data used had
      1479 records and were collected in a survey in 2003. The study was part of a
      multinational study on Gender, Alcohol, and Culture International Study
      (GENACIS). Each question on social interaction had been pre-coded in a way that
      quantified the extent of social interaction. The sum of responses on interaction
      questions gave a summative score which was used to compute summary indices on
      social interaction. Principal component analysis (PCA) was used to identify the
      best combination of variables for a social interaction index. The index was
      computed by a prediction using a PCA model developed from the selected variables.
      The index was categorised into quintiles and used in bivariate and multivariate
      logistic regression analysis of alcohol consumption and social interaction. The
      stronger the social interaction the more the likelihood of taking alcohol
      frequently (chi(trend)(2)=4.72, p<0.001). The strength of the association remains
      significant even after controlling for sex, age group and education level
      (p=0.008). The strength of relationship between social interaction and heavy
      consumption of alcohol gets weak in multivariate analysis. Communication messages
      meant to improve health, well-being and public order need to incorporate dangers
      of negative influence of social interaction.

PMID- 19406591
TI  - Antibody recognition to secreted proteins of Mycobacterium avium subsp.
      paratuberculosis in sera from infected ruminants.
AB  - Two liquid culture media to obtain secreted proteins of Mycobacterium avium
      subsp. paratuberculosis at different incubation periods were evaluated.
      Middlebrook 7H9-OADC (7H9) and Watson-Reid (WR) broths were inoculated with a
      field strain of M. paratuberculosis and growth curves determined using nonlinear
      regression analysis. Most culture filtrate (CF) proteins were of low molecular
      weight and reacted strongly against sera from cultured-positive cases of
      paratuberculosis. CF proteins obtained in WR yielded a higher number of bands and
      were detected earlier than those obtained from 7H9. A high degree of variability
      in CF protein immunoreactivity was seen among infected animals. Sera from cattle
      with clinical paratuberculosis or heavy fecal shedders of M. paratuberculosis
      reacted more intensively and to more CF proteins than did sera from other
      infected cattle. Immunoblots showed differences in antibody binding to CF
      proteins when sera were absorbed with M. avium but not with others environmental
      mycobacteria. Immunoblots with sera from infected goats and a sheep showed
      reactivity with proteins of 32, 33 and 46kDa both before and after the sera were
      absorbed with M. phlei. Antibodies found in serum of infected deer reacted with
      CF proteins in a similar way as did for cattle. These results suggest that a pool
      of CF proteins of M. paratuberculosis could be good candidates as antigens for
      serodiagnosis of paratuberculosis.

PMID- 19406590
TI  - Development of specific diagnostic test for small ruminant lentivirus genotype E.
AB  - Small ruminant lentivirus (SRLV) belonging to the highly divergent genotype E has
      recently been identified in the Italian goat breed Roccaverano. In this report we
      have developed a specific serological test based on recombinant matrix/capsid
      antigen fusion protein. Performance has been evaluated and compared with a
      similar test based on genotype B antigen. Herds under study were selected
      according to the infectious status characterized by blood PCR and sequencing.
      Results clearly showed that B and E based recombinant ELISA only detected
      homologous infection and an apparent cross-reactivity was recorded in a herd in
      which co-infection was present. Three commercially available ELISAs showed
      different abilities in detecting genotype E infection, being the whole virus
      based immunoassay the best choice. Genotype E-recombinant antigen was not
      detected in ELISA by three commercially available Mabs known to be cross-reactive
      among CAEV and MVV capsid antigens, further supporting the high divergence of the
      E genotype from others. Finally, a SRLV-free herd according to commercial ELISA
      testing, was analysed in the same area where genotype E was identified and few
      animals belonging to Roccaverano breed were found slightly reactive with the E
      antigens. Our results suggest that the prevalence of genotype E in other small
      ruminant populations may be conveniently estimated using a comparative assay
      based on a combination of genotype specific recombinant antigens and may
      highlight a wider space in which SRLVs evolve.

PMID- 19406592
TI  - Determination of the metabolites of the new designer drugs bk-MBDB and bk-MDEA in
      human urine.
AB  - This is the first report on identifying the specific metabolites of the new
      designer drugs 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one (bk-MBDB)
      and 2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one (bk-MDEA) in human
      urine using synthesized standards. Based on GC/MS and LC/MS, we identified N
      dealkylation, demethylenation followed by O-methylation, and beta-ketone
      reduction as their major metabolic pathways. The quantitative analyses by LC/MS
      revealed that both demethylenation followed by O-methylation and beta-ketone
      reduction were superior to N-dealkylation and that both bk-MBDB and bk-MDEA were
      mainly metabolized into their corresponding 4-hydroxy-3-methoxy metabolites (4-OH
      3MeO metabolites). After hydrolysis, the concentrations of 4-OH-3MeO metabolites
      and 3-hydroxy-4-methoxy metabolites of both bk-MBDB and bk-MDEA dramatically
      increased, suggesting that the metabolites mainly exist as their conjugates.

PMID- 19406594
TI  - Potential dependent superiority of gold nanoparticles in comparison to iodinated
      contrast agents.
AB  - PURPOSE: To identify the benefits in image contrast enhancement using gold
      nanoparticles (AuNPs) compared to conventional iodinated contrast media.
      MATERIALS AND METHODS: Gold nanoparticles and iodinated contrast media were
      evaluated for contrast enhancement at various X-ray tube potentials in an imaging
      phantom. Iopromide and AuNP suspension were equalized according to molar
      concentration of radiopaque element (0.5077 Mol/L). Contrast-to-noise ratio is
      used to quantify contrast enhancement. Both projectional radiographic (40-80 kVp)
      and computed tomography (CT) (80-140 kVp) imaging modalities were examined.
      RESULTS AND CONCLUSIONS: Findings indicate 89% improvement in CNR at low energies
      near the mammographic range (40 kVp). However, as expected no significant
      difference in enhancement was observed at potentials commonly used for
      angiography (around 80 kVp) probably due to the k-edge influence for iodine. At
      the highest energies typically available in computed tomography, significant
      improvement in contrast enhancement using gold nanoparticles is obtained, 114%
      greater CNR than that produced by iodine at 140 kVp. Experimental findings for 70
      120 kVp spectra correlate well with the theoretical calculations based on linear
      attenuation coefficients. Superior attenuation of gold nanoparticles at low and
      high kVp potentials support their further (pre)clinical evaluation.

PMID- 19406595
TI  - PET/CT for the staging and follow-up of patients with malignancies.
AB  - Positron emission tomography (PET) and computed tomography (CT) complement each
      other's strengths in integrated PET/CT. PET is a highly sensitive modality to
      depict the whole-body distribution of positron-emitting biomarkers indicating
      tumour metabolic activity. However, conventional PET imaging is lacking detailed
      anatomical information to precisely localise pathologic findings. CT imaging can
      readily provide the required morphological data. Thus, integrated PET/CT
      represents an efficient tool for whole-body staging and functional assessment
      within one examination. Due to developments in system technology PET/CT devices
      are continually gaining spatial resolution and imaging speed. Whole-body imaging
      from the head to the upper thighs is accomplished in less than 20 min. Spatial
      resolution approaches 2-4mm. Most PET/CT studies in oncology are performed with
      (18)F-labelled fluoro-deoxy-D-glucose (FDG). FDG is a glucose analogue that is
      taken up and trapped within viable cells. An increased glycolytic activity is a
      characteristic in many types of cancers resulting in avid accumulation of FDG.
      These tumours excel as "hot spots" in FDG-PET/CT imaging. FDG-PET/CT proved to be
      of high diagnostic value in staging and restaging of different malignant
      diseases, such as colorectal cancer, lung cancer, breast cancer, head and neck
      cancer, malignant lymphomas, and many more. The standard whole-body coverage
      simplifies staging and speeds up decision processes to determine appropriate
      therapeutic strategies. Further development and implementation of new PET-tracers
      in clinical routine will continually increase the number of PET/CT indications.
      This promotes PET/CT as the imaging modality of choice for working-up of the most
      common tumour entities as well as some of the rare malignancies.

PMID- 19406593
TI  - Simultaneous quantification of buprenorphine, norbuprenorphine, buprenorphine
      glucuronide and norbuprenorphine-glucuronide in human umbilical cord by liquid
      chromatography tandem mass spectrometry.
AB  - A LCMS method was developed and validated for the simultaneous determination of
      buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine-glucuronide (BUP
      Gluc) and norbuprenorphine-glucuronide (NBUP-Gluc) in human umbilical cord.
      Quantification was achieved by selected ion monitoring of precursor ions m/z
      468.4 for BUP; 414.3 for NBUP; 644.4 for BUP-Gluc and 590 for NBUP-Gluc. BUP and
      NBUP were identified by MS(2), with m/z 396, 414 and 426 for BUP, and m/z 340,
      364 and 382 for NBUP. Glucuronide conjugates were identified by MS(3) with m/z
      396 and 414 for BUP-Gluc and m/z 340 and 382 for NBUP-Gluc. The assay was linear
      1-50 ng/g. Intra-day, inter-day and total assay imprecision (%RSD) were <14.5%,
      and analytical recovery ranged from 94.1% to 112.3% for all analytes. Extraction
      efficiencies were >66.3%, and process efficiency >73.4%. Matrix effect ranged, in
      absolute value, from 3.7% to 7.4% (CV<21.8%, n=8). The method was selective with
      no endogenous or exogenous interferences from 41 compounds evaluated. Sensitivity
      was high with limits of detection of 0.8 ng/g. In order to prove method
      applicability, an authentic umbilical cord obtained from an opioid-dependent
      pregnant woman receiving BUP pharmacotherapy was analyzed. Interestingly, BUP was
      not detected but concentrations of the other metabolites were NBUP-Gluc 13.4
      ng/g, BUP-Gluc 3.5 ng/g and NBUP 1.2 ng/g.

PMID- 19406596
TI  - Non-invasive assessment of hepatic fat accumulation in chronic hepatitis C by 1H
      magnetic resonance spectroscopy.
AB  - BACKGROUND: Liver biopsy is the standard method for diagnosis of hepatic
      steatosis, but is invasive and carries some risk of morbidity. AIMS AND METHODS:
      Quantification of hepatocellular lipid content (HCL) with non-invasive single
      voxel (1)H magnetic resonance spectroscopy (MRS) at 3T was compared with
      histological grading and biochemical analysis of liver biopsies in 29 patients
      with chronic hepatitis C. Body mass index, indices of insulin resistance
      (homeostasis model assessment index, HOMA-IR), serum lipids and serum liver
      transaminases were also quantified. RESULTS: HCL as assessed by (1)H MRS linearly
      correlated (r=0.70, p<0.001) with histological evaluation of liver biopsies and
      was in agreement with histological steatosis staging in 65% of the patients.
      Biochemically assessed hepatic triglyceride contents correlated with HCL measured
      with (1)H MRS (r=0.63, p<0.03) and allowed discriminating between none or mild
      steatosis versus moderate or severe steatosis. Patients infected with hepatitis C
      virus genotype 3 had a higher prevalence of steatosis (62%) which was not
      explained by differences in body mass or whole body insulin resistance. When
      these patients were excluded from correlation analysis, hepatic fat accumulation
      positively correlated with insulin resistance in the remaining hepatitis C
      patients (HCL vs. HOMA-IR, r=0.559, p<0.020, n=17). CONCLUSION: Localized (1)H
      MRS is a valid and useful method for quantification of HCL content in patients
      with chronic hepatitis C and can be easily applied to non-invasively monitoring
      of steatosis during repeated follow-up measurements in a clinical setting.

PMID- 19406597
TI  - Quantification of trans-resveratrol and its metabolites in rat plasma and tissues
      by HPLC.
AB  - trans-Resveratrol, a polyphenol from grapes, is being recognized as a bioactive
      agent with potential beneficial effects on health. However, little is known about
      its distribution in the organism mainly because of the lack of accurate and
      precise detection methods. Consequently the aim of the present study was to
      develop a methodology of extraction and quantification of trans-resveratrol and
      its metabolites in plasma, brain, testis, liver, lungs and kidney by HPLC. To
      this end, the time of homogenization and liquid extraction were adapted to the
      different tissues. The methods were validated using homogenized tissues spiked
      with pure trans-resveratrol. The precision (% R.S.D.) ranged from 3.7% in testis
      to 13.2% in lungs. Recoveries were 98.5+/-3.2% (liver), 100.1+/-1.8% (kidney),
      96.5+/-7.6% (lungs), 99.0+/-0.7% (brain) and 103+/-2.7% (testicle). The limits of
      detection ranged from 5.5 nM in testis to 11.2 nM in kidney. After validation,
      the methods were applied to the assessment of the bioavailability and
      distribution of trans-resveratrol in rats after the intravenous administration of
      15 mg/kg. At 90 min, trans-resveratrol and its glucuronide and sulfate conjugates
      were widely distributed in all the tissues studied. The highest concentrations
      (nmol/g tissue) were found in kidney (resveratrol: 1.45+/-0.35; glucuronide:
      2.91+/-0.19; sulfate: not detected), and the lowest in brain (resveratrol: 0.17+/
      0.04; glucuronide: not detected; sulfate: 0.04+/-0.01). In conclusion, accurate
      and reproducible methods have been described to identify target tissues of
      resveratrol as a first step to understand its mechanisms of action in vivo.

PMID- 19406598
TI  - Microsomal metabolism of calycosin, formononetin and drug-drug interactions by
      dynamic microdialysis sampling and HPLC-DAD-MS analysis.
AB  - A dynamic microdialysis sampling method with liquid chromatography-diode array
      detection and time-of-flight mass spectrometry (LC-DAD-TOF/MS) analysis was
      developed to investigate rat microsomal metabolisms of calycosin and
      formononetin, and their drug-drug interactions. Two hydroxylated metabolites from
      calycosin, and three hydroxylated or 4'-O-demethylated derivatives from
      formononetin were detected and identified after co-incubation with microsomes.
      Calibration curves offered linear ranges of two orders of magnitude with
      r(2)>0.999 for calycosin, formononetin and daidzein. The quantitative LC method
      provides a range of 0.028-0.034microg/mL for limits of detection, overall
      precision less than 5% and accuracy less than 3% by RSD. Besides, calycosin and
      formononetin were found to produce the depressive effect on the CYP450 enzyme
      reaction, and inhibit phase I enzyme reaction of each other when they are
      concurrent. Dynamic microdialysis sampling with LC-DAD-TOF/MS analysis developed
      in this work is a powerful tool for in vitro metabolism studies of drugs and
      metabolic interactions.

PMID- 19406600
TI  - Tetanus-diptheria-acellular pertussis (Tdap): tap the resources of the emergency
      department to fight pertussis.

PMID- 19406599
TI  - Solid phase extraction-spectrophotometric determination of salicylic acid using
      magnetic iron oxide nanoparticles as extractor.
AB  - This method shows a novel, fast and simple solid phase extraction
      spectrophotometric procedure for preconcentration and determination of salicylic
      acid (SA) in blood serum using magnetic iron oxide nanoparticles (MIONs) as
      extractor. It is shown that the novel magnetic nano-adsorbent is quite efficient
      for fast adsorption of SA at 25 degrees C. Various parameters affecting the
      adsorption of SA on MIONs, such as pH of solution, type, volume and concentration
      of desorbing reagent and amount of adsorbent and matrix effects, have been
      investigated. The calibration graph for the determination of SA was linear in the
      range of 0.025-1.250microgmL(-1). The limit of detection (LOD) based on three
      times the standard deviation of the blank (3S(b)) was 5.5x10(-3)microgmL(-1)
      (n=10) for SA. The intra-day precision (R.S.D.) was below 10.1% and inter-day
      R.S.D. was less than 17.5%, while accuracy (relative error R.E.) was within +/
      3.6 determined from quality control samples for salicylic acid (SA) which
      corresponded to requirement of the guidance of Food and Drug Administration
      (FDA). The preconcentration factor of 100 was achieved in this method. The
      proposed procedure has been successfully applied to the determination of SA in
      blood serum.

PMID- 19406602
TI  - Positional skin color changes helping in the diagnosis of superior vena caval
      obstruction syndrome.

PMID- 19406601
TI  - Charles Bonnet syndrome: three cases in the emergency department.
AB  - BACKGROUND: Charles Bonnet Syndrome (CBS) is a cause of visual hallucinations in
      elderly patients that is often unrecognized by emergency physicians and has a
      relatively benign course. As the population ages, it is likely that the number of
      cases of CBS will increase (and thus, the numbers of those who present to an
      Emergency Department [ED] will be increasing). OBJECTIVES: The case reports
      presented in this article will facilitate the recognition of CBS by the emergency
      physician. CASE REPORT: We describe 3 patients who presented to one ED for visual
      disturbances and were diagnosed with CBS in a 4-month time period. CONCLUSION:
      Recognition of this unusual but stereotypical cause of visual disturbances
      facilitates an accurate diagnosis, and spares patients the time and expense of
      blood testing, imaging, and consultations. If emergency physicians begin to
      recognize this benign entity, we can provide improved (and safer) patient care
      with appropriate ED interventions.

PMID- 19406603
TI  - Bronchial rupture by an unusual mechanism of thoracic hyperextension.
AB  - BACKGROUND: Tracheobronchial disruption usually occurs in the setting of blunt
      chest trauma and may be overlooked due to co-existing injuries and non-specific
      symptoms. OBJECTIVES: Review the mechanism, diagnosis, and therapeutic management
      of tracheobronchial disruption. CASE REPORT: We present a case of a young woman
      with a bronchial rupture 3 weeks after accidental strangulation. Initial
      diagnosis was delayed due to the unusual presentation. She presented with acute
      respiratory failure and hemodynamic collapse after slowly progressive shortness
      of breath with exertion. CONCLUSIONS: This case report provides an overview of
      the clinical features of bronchial disruption by highlighting the varying degrees
      of clinical presentation and management. Urgent bronchoscopy is indicated for
      diagnosis, and surgical intervention for treatment.

PMID- 19406604
TI  - Assessment of risk tolerance for adverse events in emergency department chest
      pain patients: a pilot study.
AB  - BACKGROUND: Emergency physicians commonly encounter low-probability/high
      morbidity decisions, and chest pain is a prime example. Negative outcomes are
      improbable but feared, resulting in substantially more patients admitted for
      chest pain than have important disease. The literature gives little guidance on
      patient preferences for decision-making when the negative outcomes are unlikely
      but potentially severe. OBJECTIVES: The objective of this pilot study was to
      assess the tolerance of Emergency Department (ED) patients with chest pain for
      adverse events occurring within 2 weeks of the episode. METHOD: We recruited a
      convenience sample of patients with a chief complaint of chest pain from the ED
      of an urban tertiary-care referral center. Each subject was interviewed to
      determine demographic information, perceived health status, insurance status, and
      tolerance for adverse events related to chest pain. Adverse events were defined
      loosely but were suggested to be heart attack, the need for emergency cardiac
      surgery, or death. The risk tolerance question was framed by describing a
      specific numeric risk and determining at what risk the patient switched from
      desiring hospital admission to desiring discharge; we termed this the decision
      threshold. RESULTS: Sixty-eight (68) subjects were included. Fifty-four percent
      of subjects were male, 60% were African-American, and 35% were white; 40% of the
      subjects classified themselves as being of average health. Of the 31 subjects who
      had prior heart trouble, 48% (n = 15) stated they had a prior heart attack and
      19% (n = 6) an irregular heartbeat. The median decision threshold, or the
      acceptable personal risk of an adverse event for a person to forego admission to
      hospital, was 6.5% (interquartile range 0.5-22.9%). The mode was 0.5%, and 44%
      (30/68) of subjects had a decision threshold of 2% or less. There was no obvious
      pattern for most of these explanatory variables, though there was a suggestion
      that race may affect patients' risk tolerance. CONCLUSIONS: There is substantial
      variation in patients' reported tolerance for adverse events from ED chest pain.
      Further investigation of this phenomenon may lead to better decision-making.

PMID- 19406605
TI  - Wernicke's encephalopathy presenting as acute psychosis after gastric bypass.
AB  - BACKGROUND AND OBJECTIVES: Patients frequently present to the Emergency
      Department (ED) with psychiatric complaints. The differential diagnosis for acute
      psychosis is extensive, and determining a possible etiology requires a thorough
      history and physical. Small details can help the physician in differentiating
      organic disease from non-organic disease. Many times patients are thought to be
      "crazy" without a thorough history and physical being done. CASE REPORT: In this
      case, the diagnosis hinged on the history of having gastric bypass surgery. A
      thorough physical examination was performed, and the patient had neurologic
      findings suggestive of severe thiamine deficiency. The patient's thiamine level
      was low. The patient was started on i.v. thiamine and slowly began to recover.
      CONCLUSION: Cerebral beriberi, more commonly known as Wernicke's encephalopathy,
      is a difficult diagnosis to make in the ED. A thorough neurologic examination is
      difficult to perform in the ED environment, but it is necessary when trying to
      determine the etiology of the patient's altered mental status. The number of
      patients with Wernicke's encephalopathy may increase with bariatric surgery
      becoming more common. This disease can present with a wide variety of findings,
      and the classic triad is not very common. With this in mind, the physician should
      have a low threshold for administering thiamine intravenously.

PMID- 19406607
TI  - Pulse oximetry using a disposable finger sensor placed on the forehead in hypoxic
      patients.
AB  - BACKGROUND: Disposable pulse oximetry sensors designed for the finger are
      sometimes placed on the forehead. Although finger sensors have not been designed
      to accurately measure arterial oxygen saturation when placed on other body parts,
      they are used on the forehead when an oximetry waveform cannot be obtained from
      the finger. OBJECTIVES: The purpose of this prospective observational study was
      to measure the agreement between disposable transmittal sensors placed on the
      finger and the same sensors placed on the forehead. METHODS: We used a
      convenience sample of hypoxic emergency department patients. Patients were
      attached to three oximeters: 1) a non-disposable finger sensor (reference); 2) a
      disposable finger sensor placed on the finger; and 3) a disposable finger sensor
      placed on the forehead. Data were analyzed using the Bland-Altman method. A
      difference of 5% was considered clinically significant. RESULTS: Twenty-five
      patients were approached, and 20 were enrolled. Eleven of the patients had an
      absolute difference between the disposable finger sensor placed on the finger
      compared to the forehead > or = 5%. CONCLUSION: Pulse oximetry measurements taken
      on the forehead using a disposable finger sensor were inaccurate in over half of
      the subjects. Therefore, disposable finger oximetry sensors should not be placed
      on the forehead.

PMID- 19406606
TI  - Hollow viscus injury.
AB  - BACKGROUND: Hollow viscus injuries are uncommon and occur in approximately 1% of
      all blunt trauma patients. DISCUSSION: These injuries are often not suspected and
      are difficult to diagnosis. Morbidity and mortality are high, and a negative
      abdominal computed tomography is not sufficient to rule out these injuries in
      certain clinical scenarios. CONCLUSION: Using a case-based approach, the
      epidemiology and diagnostic pathways to manage hollow viscus injuries are
      reviewed.

PMID- 19406608
TI  - Effectiveness of a computer tailored physical activity intervention in
      adolescents compared to a generic advice.
AB  - OBJECTIVE: To investigate the differences in effects of a computer tailored
      physical activity advice as compared to generic information in adolescents.
      METHODS: Students (mean age, 14.6+/-1.2) out of 90 classes from six different
      Flemish schools were randomly assigned to the tailored intervention (n=563) or
      the generic non-tailored intervention (n=608) condition. Both interventions
      included information on public health recommendations and tips on becoming more
      active. Participants in both groups received their assessment and feedback at
      baseline, at 4 weeks and at 3 months during school hours. Physical activity
      levels were determined using an adolescent adaptation of the International
      Physical Activity Questionnaire (IPAQ). RESULTS: After 4 weeks, almost all
      physical activity scores increased over time in both the generic and the tailored
      intervention group. No differences between groups were found (all F< or =0.07).
      After 3 months, the generic intervention was more effective for increasing
      'walking in leisure time' among students not complying with recommendations. For
      all other physical activity scores, no differences between groups were found (all
      F< or =2.3). CONCLUSIONS: In contrast to the expectations, changes in physical
      activity scores did not differ between the tailored and the non-tailored
      intervention group. For most of the physical activity scores increases were found
      in both groups.

PMID- 19406609
TI  - The information needs of partners and family members of cancer patients: a
      systematic literature review.
AB  - OBJECTIVE: This review examined the extent to which the information needs of
      partners and family members of cancer patients has been addressed in the
      literature. METHODS: We conducted a systematic search of four databases for
      papers published between 1998 and 2008 which assessed the information needs of
      partners and/or family members of adult cancer patients. RESULTS: Thirty-two
      papers were included in the review. Eleven categories of information need were
      identified. There was a predominant focus on breast or prostate cancer, leaving a
      knowledge gap in relation to other cancers. Few papers moved beyond the diagnosis
      and initial treatment phase, and most did not distinguish between met and unmet
      needs. Those that did, indicated that partners/family members are more likely to
      have unmet needs for information about supportive care than for medical
      information. The concept of 'information need' was generally poorly developed and
      theorised in the papers. CONCLUSION: Establishing the information needs of
      partners and family members of cancer patients is an important, but as yet
      neglected, area of research. In order to develop our understanding of this area
      more empirical research, with sound conceptual and theoretical foundations is
      required.

PMID- 19406611
TI  - [Quality and healthcare safety: a cultural evolution or revolution].

PMID- 19406612
TI  - [Haemorrhagic shock caused by an intramural duodenal haematoma complicating the
      endoscopic treatment of a peptic ulcer].

PMID- 19406610
TI  - Processes and outcomes of head and neck cancer patients from geographically
      disparate regions of the UK. A comparison of Scottish and English cohorts.
AB  - AIM: The aim of this paper was to compare demographics, treatment and outcomes
      from two large prospective audits of head and neck cancer patients in two
      disparate regions of the UK. METHODS: In the Scottish Audit of Head and Neck
      Cancer (SAHNC) a total of 1910 patients with new head and neck cancers were
      registered in a two year period from September 1999 to August 2001. The South and
      West Audit of Head and Neck Cancer (SWAHN) was carried out in three phases
      between 1996 and 2002 with a total of 2050 cases. RESULTS: There were more men in
      SAHNC than SWAHN (71% vs 67%, p<0.01) and patients in SAHNC presented at a
      younger age (76% aged 45-74 compared with 64%, p<0.001). Significantly more
      patients in Scotland had advanced (stage III/IV) laryngeal cancer (44% vs 30%,
      p<0.001). The overall disease specific five year survival was 54.5 for SAHNC and
      54.2 for SWAHN. CONCLUSION: This comparison of large head and neck cancer cohorts
      provides important data to base UK head and neck cancer care and hypotheses
      regarding pathogenesis and the effects of treatment processes. Given the
      heterogeneity in disease, patient and healthcare characteristics between the two
      regions, the similarities in survival and process outcomes are striking.

PMID- 19406613
TI  - Quantitative analysis of facial movement--a review of three-dimensional imaging
      techniques.
AB  - Objective analysis of facial movement forms an important consideration in the
      assessment and outcome of several medical disciplines. Technological advances in
      the field of medical imaging have meant techniques to measure facial movement
      have evolved from subjective grading scales to facial-marker-based tracking
      systems to the most recent development of true three-dimensional marker-free
      systems. The aim of this paper is to provide a comprehensive review of the
      literature in this evolving field of medical imaging particularly focusing on
      three-dimensional analysis of facial movement and outlining the current concepts
      in objective analysis of the data set.

PMID- 19406614
TI  - A textural approach for mass false positive reduction in mammography.
AB  - During the last decade several algorithms have been proposed for automatic mass
      detection in mammographic images. However, almost all these methods suffer from a
      high number of false positives. In this paper we propose a new approach for
      tackling this false positive reduction problem. The key point of our proposal is
      the use of Local Binary Patterns (LBP) for representing the textural properties
      of the masses. We extend the basic LBP histogram descriptor into a spatially
      enhanced histogram which encodes both the local region appearance and the spatial
      structure of the masses. Support Vector Machines (SVM) are then used for
      classifying the true masses from the ones being actually normal parenchyma. Our
      approach is evaluated using 1792 ROIs extracted from the DDSM database. The
      experiments show that LBP are effective and efficient descriptors for
      mammographic masses. Moreover, the comparison with current methods illustrates
      that our proposal obtains a better performance.

PMID- 19406615
TI  - Unilateral expansion of a narrow mandibular dental arch combined with bimaxillary
      osteotomies in a patient with hypoglossia.
AB  - A 23-year-old female with hypoglossia, who had a narrow mandibular dental arch,
      was treated using the gradual expansion technique. Three lower incisors were
      missing and the right molar occlusion showed a scissor bite. Her speech was
      acceptable. Gradual unilateral expansion of the mandibular alveolar bone was
      performed. Orthodontic tooth alignment was performed prior to surgical treatment.
      A tooth-borne expander was devised using a hyrax-type screw to move the inclined
      right alveolar bone into an upright position. Alveolar bone osteotomies were
      performed under general anesthesia and the expander was placed in the mandibular
      dental arch. After a 5-day latency period, the screw was activated for 21 days.
      After expansion, the width of the mandibular dental arch increased by 10mm at the
      first molar region and the right molars were moved to an upright position. After
      a consolidation period of 7 days, simultaneous two-jaw surgery that combined Le
      Fort I osteotomy and intraoral vertical ramus osteotomies was performed to obtain
      a stable occlusion. After post-surgical orthodontic and prosthodontic treatment,
      her occlusion improved without deterioration of her speech. The results indicate
      that this technique is useful for unilateral expansion of distorted mandibular
      alveolar process.

PMID- 19406616
TI  - Gold weight implants in the management of paralytic lagophthalmos.
AB  - Lagophthalmos secondary to facial nerve damage can lead to corneal exposure and
      eventually blindness. Appropriate management depends on the severity and likely
      duration of recovery. Upper eyelid gold implants play an important role in the
      medium and long term management of this condition. The authors report their
      experience with 16 consecutive patients who underwent gold weight implantation of
      the upper eyelids for correction of paralytic lagophthalmos and describe their
      surgical technique. The mean age of the patients was 70 years with a male
      predominance (M:F=3.2:1). Radical parotidectomy (69%) was the most common reason
      for the intervention. The mean weight of the implant was 0.95 g. There were no
      intraoperative or immediate postoperative complications. One implant (6%) was
      extruded and one patient (6%) had residual lagophthalmos and required a heavier
      implant. 15 of the 16 patients were satisfied with the outcome and all had
      adequate lid closure at last follow up.

PMID- 19406617
TI  - Temporomandibular joint osteoarthritis: an open label trial of 76 patients
      treated with arthrocentesis plus hyaluronic acid injections.
AB  - This study is an open-label trial on a sample of 76 consecutive patients with
      temporomandibular joint (TMJ) osteoarthritis treated with a cycle of five weekly
      arthrocenteses plus hyaluronic acid injections. Patients had a diagnosis of
      osteoarthritis according to the Research Diagnostic Criteria for
      Temporomandibular Disorders (RDC/TMD Axis I Group IIIb). They underwent a cycle
      of five arthrocenteses with injections (1 per week) of 1ml hyaluronic acid and
      four follow-up assessments after the end of the treatment (at 1 week, 1 month, 3
      months, 6 months). At each appointment, several subjective and objective outcome
      variables were assessed to test the efficacy of the treatment protocol. Marked
      improvements were reported for all variables during the treatment phase. The
      improvements were maintained over the 6-month follow-up period. The p-value of
      the multivariate permutation test for the efficacy of the treatment over time
      (with Tippett's combination) was 0.001, and significant changes at the end of the
      follow-up period were detected for almost all the outcome variables. Data from
      this study lend further support to the usefulness of serial hyaluronic acid
      injections performed after arthrocentesis for the treatment of TMJ osteoarthritis
      and for the maintenance of improvements over a 6-month follow-up period.

PMID- 19406618
TI  - Early bone response to sandblasted, dual acid-etched and H2O2/HCl treated
      titanium implants: an experimental study in the rabbit.
AB  - The aim of this study was to evaluate the influence of a roughened H(2)O(2)/HCl
      heat-treated titanium surface on peri-implant bone formation at an early stage in
      vivo. 24 Ti(6)Al(4)V alloy implants were used; half were treated by sandblasted
      and dual acid-etched treatments (control group), while the others were treated by
      sandblasted, dual acid-etched and H(2)O(2)/HCl heat treatments (test group). The
      morphology and roughness were analyzed by field emission SEM and atomic force
      microscopy. The implants were inserted into the femora of 12 adult white rabbits.
      After 2 and 4 weeks, femora block specimens were prepared for histological and
      histomorphometric analysis. SEM micrographs showed that multilevel and different
      sized pits were formed on both surfaces. New bone formation was observed on both
      implant surfaces. Test implants demonstrated a greater mean percentage of bone
      implant contact as compared with controls at 2 (46.84 vs. 41.81, p=0.000) and 4
      weeks (49.43 vs. 44.87, p=0.006) of healing. It is concluded that the
      H(2)O(2)/HCl heat-treated rough titanium surface promoted enhanced bone
      apposition during the early stages of new bone formation around the implant.

PMID- 19406619
TI  - Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate
      in the maximal electroshock seizure and chimney tests in mice: a comparative
      study.
AB  - The aim of this study was to determine and compare the anticonvulsant and acute
      adverse (neurotoxic) effects of imperatorin and osthole (two natural coumarin
      derivatives) with valproate (a classical antiepileptic drug) in the maximal
      electroshock seizure and chimney tests in mice. The anticonvulsant and acute
      adverse effects of imperatorin, osthole and valproate were determined at 15, 30,
      60 and 120 min after their systemic (i.p.) administration. The evaluation of time
      course and dose-response relationships for imperatorin, osthole and valproate in
      the maximal electroshock seizure test revealed that the compounds produced a
      clear-cut antielectroshock action in mice and the experimentally derived ED(50)
      values for imperatorin ranged between 167 and 290 mg/kg, those for osthole ranged
      from 253 to 639 mg/kg, whereas the ED(50) values for valproate ranged from 189 to
      255 mg/kg. The evaluation of acute neurotoxic effects in the chimney test
      revealed that the TD(50) values for imperatorin ranged between 329 and 443 mg/kg,
      the TD(50) values for osthole ranged from 531 to 648 mg/kg, while the TD(50)
      values for valproate ranged from 363 to 512 mg/kg. The protective index (as a
      ratio of TD(50) and ED(50) values) for imperatorin ranged between 1.13 and 2.60,
      for osthole ranged from 0.83 to 2.44, and for valproate ranged between 1.72 and
      2.00. In conclusion, both natural coumarin derivatives deserve more attention
      from a preclinical point of view as compounds possessing some potentially
      favorable activities in terms of suppression of seizures, quite similar to those
      reported for valproate.

PMID- 19406621
TI  - BDNF is not associated with schizophrenia: data from a Japanese population study
      and meta-analysis.
AB  - A variety of evidence suggests brain-derived neurotrophic factor (BDNF) as a
      candidate gene for schizophrenia, and several genetic studies have shown a
      significant association between the disease and certain SNPs within BDNF
      (specifically, Val66Met and C270T). According to a recent study, the functional
      microsatellite marker BDNF-LCPR (BDNF-linked complex polymorphic region), which
      affects the expression level of BDNF, is associated with bipolar disorder. The
      goals of our current study were to 1) evaluate the quality of HapMap-based
      linkage disequilibrium (LD) tagging of BDNF-LCPR, 2) examine whether these
      tagging SNPs are associated with schizophrenia in a Japanese population, and 3)
      conduct a meta-analysis of the two most extensively studied polymorphisms:
      Val66Met and C270T. We genotyped eight tagging SNPs, including Val66Met and
      C270T. Our LD evaluation showed that BDNF-LCPR could be represented by these
      tagging SNPs in controls (with 73.5% allelic coverage). However, the functional
      A1 allele was not captured due to its low minor allele frequency (2.2%). In a
      case-control study (1117 schizophrenics and 1102 controls), no association was
      found in single-marker or multimarker analysis. Moreover, in a meta-analysis, the
      Val66Met polymorphism was not associated with schizophrenia, whereas C270T showed
      a trend for association in a fixed model (p=0.036), but not in a random model
      (p=0.053). From these findings, we conclude that if BDNF is indeed associated
      with schizophrenia, the A1 allele in BDNF-LCPR would be the most promising
      candidate. Further LD evaluation, as well as an association study in which BDNF
      LCPR is genotyped directly, would be required for a more conclusive result.

PMID- 19406622
TI  - Proton magnetic resonance spectroscopy in subjects with high genetic risk of
      schizophrenia: investigation of anterior cingulate, dorsolateral prefrontal
      cortex and thalamus.
AB  - OBJECTIVE: Reduced N-acetylaspartate levels in regions of the frontal cortex,
      including the anterior cingulate cortex, dorsolateral prefrontal cortex, and
      thalamus, involved in the pathophysiology of schizophrenia suggest that brain
      metabolite abnormalities may be a marker of genetic vulnerability to
      schizophrenia. We used proton magnetic resonance spectroscopy (H-MRS) to acquire
      absolute concentrations of brain metabolites in subjects with a high genetic risk
      of schizophrenia to investigate the potential relationship between unexpressed
      genetic liability to schizophrenia and neuronal dysfunction. METHOD: Included in
      the study were 22 subjects who had at least two relatives with schizophrenia
      (high genetic risk group) and 22 controls with no second-degree relatives with
      schizophrenia. Absolute concentrations of N-acetylaspartate, creatine, choline,
      glutamate/glutamine, and myo-inositol and the ratios of metabolites in the
      anterior cingulate cortex, left dorsolateral prefrontal cortex, and left thalamus
      were measured using H-MRS at 1.5 Tesla. RESULTS: Relative to the controls, the
      high genetic risk group showed significant differences in absolute metabolite
      levels in the spectra of the regions of the left thalamus, including significant
      decreases in N-acetylaspartate, creatine, and choline concentrations.
      CONCLUSIONS: The study points to neuronal dysfunction, and in particular thalamic
      dysfunction, as a key region of the vulnerability marker of schizophrenia.
      Further studies should examine the nature of the thalamus more intensively to
      further our understanding of thalamic dysfunction as a vulnerability marker.

PMID- 19406623
TI  - Cardio-respiratory coupling indicates suppression of vagal activity in acute
      schizophrenia.
AB  - Altered amygdala activity in patients with schizophrenia can influence
      respiratory patterns and consequently cardiovascular parameters. Hence, we
      examined respiration and heart rate time series complexity as well as coupling of
      both signals. Electrocardiograms and respiratory signals were obtained from 25
      unmedicated patients with schizophrenia and controls. Approximate entropy (ApEn)
      was calculated for heart and respiratory rates as well as cross-ApEn reflecting
      coupling of both signals. Coupling was decreased indicating diminished vagal
      modulation at the brain stem level. Regularity of breathing correlated with
      disease severity. These data might reflect a lack of inhibitory control over
      brainstem centers in schizophrenia.

PMID- 19406624
TI  - KPC-2-producing Enterobacter cloacae in two cities from Southern Brazil.

PMID- 19406625
TI  - In vitro activity of ceftobiprole against Acinetobacter baumannii clinical
      isolates.
AB  - Acinetobacter baumannii is a multiresistant opportunistic nosocomial pathogen
      responsible for outbreaks worldwide. The main infection caused by this
      microorganism is nosocomial pneumonia, in particular ventilator-associated
      pneumonia in patients in Intensive Care Units. Treatment of these nosocomial
      infections is becoming problematic because the level of resistance to
      antimicrobial agents is rising. Ceftobiprole is a new cephalosporin with activity
      against Gram-positive and Gram-negative pathogens. This study evaluated the in
      vitro activity of ceftobiprole against a collection of 58 A. baumannii clinical
      isolates and showed that the activity of ceftobiprole was superior to ceftazidime
      and cefepime when the bla(ADC)-like gene was not expressed or was expressed at a
      low level.

PMID- 19406626
TI  - Effect of short term treatment of L-carnitine on tissue ACE activity in
      streptozotocin-induced diabetic rats.
AB  - Diabetes is commonly related to the both microvascular as well as macrovascular
      complications. It appears that both metabolic and hemodynamic factors interact to
      create these problems. In this study the effects of orally administered L
      carnitine, a natural amino acid, on ACE activity in streptozotocin (STZ)-induced
      diabetic rats were investigated. Streptozotocin (60mg/kg body weight) was given
      intraperitoneally. Fifty male Sprague-Dawley rats were divided into four groups:
      untreated normal (C), L-carnitine treated normal (CT), untreated diabetics (D), L
      carnitine-treated diabetics (DT). CT and DT received daily L-carnitine 1g/kg
      orally for 3 weeks after inducing diabetes. The ACE activities in aorta, heart
      and kidney homogenates was measured at the end of 3 weeks. They were
      significantly increased in D compared to C group (P<0.05) and significantly
      decreased in aorta, heart and kidney in DT compared to D group. In conclusion, L
      carnitine can reduce tissue ACE activity in aorta, heart and kidney in
      streptozotocin diabetic rats, which may be due to higher NO production.

PMID- 19406620
TI  - The role of neurosteroids in the pathophysiology and treatment of catamenial
      epilepsy.
AB  - Catamenial epilepsy is a multifaceted neuroendocrine condition in which seizures
      are clustered around specific points in the menstrual cycle, most often around
      perimenstrual or periovulatory period. Generally, a twofold or greater increase
      in seizure frequency during a particular phase of the menstrual cycle could be
      considered as catamenial epilepsy. Based on this criteria, recent clinical
      studies indicate that catamenial epilepsy affects 31-60% of the women with
      epilepsy. Three types of catamenial seizures (perimenstrual, periovulatory and
      inadequate luteal) have been identified. However, there is no specific drug
      available today for catamenial epilepsy, which has not been successfully treated
      with conventional antiepileptic drugs. Elucidation of the pathophysiology of
      catamenial epilepsy is a prerequisite to develop specific targeted approaches for
      treatment or prevention of the disorder. Cyclical changes in the circulating
      levels of estrogens and progesterone play a central role in the development of
      catamenial epilepsy. There is emerging evidence that endogenous neurosteroids
      with anticonvulsant or proconvulsant effects could play a critical role in
      catamenial epilepsy. It is thought that perimenstrual catamenial epilepsy is
      associated with the withdrawal of anticonvulsant neurosteroids. Progesterone and
      other hormonal agents have been shown in limited trials to be moderately
      effective in catamenial epilepsy, but may cause endocrine side effects. Synthetic
      neurosteroids, which enhance the tonic GABA-A receptor function, might provide an
      effective approach for the catamenial epilepsy therapy without producing hormonal
      side effects.

PMID- 19406627
TI  - [Periorbital swelling in newborn].

PMID- 19406628
TI  - Age changes in the human oculomotor nerve - a stereological study.
AB  - The oculomotor nerve (ON) provides motor innervation to the eyeball and exhibits
      alterations in various physiological and pathological conditions, which may
      result in abnormal ocular movement. Although the nerve has been studied in
      detail, very few data are available regarding its morphology and changes with
      aging. Hence, in the present investigation, the neural and connective tissue
      organizations of the pre-cavernous part of the ON were studied in order to
      provide sequential data regarding age-related morphological changes. Thirty-eight
      ON from cadavers aged from 40 post-natal days to 78 years were studied. Cross
      sections of the nerve revealed a poorly defined multifascicular arrangement with
      predominant myelinated fibres of various calibres randomly intermingled with
      unmyelinated fibres. Small- and medium-sized fibres (probably parasympathetic)
      were mainly located at the junction of the central and the paracentral zones of
      the nerves. Using unbiased stereological techniques, the total number of the
      axons, the area of the myelinated fibres and myelin sheath thickness were
      estimated. The cross-sectional area of the nerve increased significantly up to
      the third decade. The minimal and maximal total number and area of myelinated
      axons varied from 17,000 to 21,000 and from 8.95 to 14.02 microm(2),
      respectively. There was a significant increase in the myelin thickness of axons
      with age. Connective tissue gradually increased in later decades and was more
      pronounced in the eighth decade. The present study provides novel baseline
      morphometric data on the ON that would be of help to future studies.

PMID- 19406629
TI  - Protection of hippocampal slices against hypoxia/hypoglycemia injury by a
      Gynostemma pentaphyllum extract.
AB  - In transverse hippcampus slices a short period of hypoxia/hypoglycemia induced by
      perfusion with O(2)/glucose-free medium caused early loss and incomplete
      restoration of evoked field potentials to only 50% in the CA(1) region. We report
      about a study investigating the effect of an ethanolic Gynostemma pentaphyllum
      extract in this system. When given with reperfusion the extract completely
      protected the cells of the slices from functional injury. The extract also
      protected at the subcellular level isolated mitochondria which had been subjected
      to hypoxia/reoxygenation in combination with elevated extramitochondrial Ca(2+)
      concentration from functional injury. In isolated mitochondria the extract
      protected from Ca(2+)-induced opening of the mitochondrial permeability
      transition pore and reduced lipid peroxidation. Our data demonstrate that the
      ethanolic extract of Gynostemma pentaphyllum has a high potential to protect from
      ischemia/reperfusion injury. It should be beneficial as prophylactic nutrition
      supplement and during revascularization of arterial blood vessels from stroke and
      other ischemic events such as coronary occlusion.

PMID- 19406630
TI  - Activity of sap from Croton lechleri on rat vascular and gastric smooth muscles.
AB  - The effects of red sap from Croton lechleri (SdD), Euphorbiaceae, on vascular and
      gastric smooth muscles were investigated. SdD, from 10 to 1000 microg/ml, induced
      concentration-dependent vasoconstriction in rat caudal arteries, which was
      endothelium-independent. In arterial preparations pre-constricted by
      phenylephrine (0.1 microM) or KCl (30 mM), SdD also produced concentration
      dependent vasoconstriction. To study the mechanisms implicated in this effect we
      used selective inhibitors such as prazosin (0.1 microM), an antagonist of
      alpha(1)-adrenoceptors, atropine (0.1 microM), an antagonist of muscarinic
      receptors, and ritanserin (50 nM), a 5-HT(2A) antagonist; none of these
      influenced vasoconstriction caused by SdD. Likewise, nifedipine (50 nM), an
      inhibitor of L-type calcium channels, did not modify the action of SdD. Capsaicin
      (100 nM), an agonist of vanilloid receptors, also did not affect vasoconstriction
      by SdD. We also investigated the action of SdD (10-1000 microg/ml) on rat gastric
      fundus; per se the sap slightly increased contractile tension. When the gastric
      fundus was pre-treated with SdD (100 microg/ml) the contraction induced by
      carbachol (1 microM) was increased, whereas that by KCl (60mM) or capsaicin (100
      nM) were unchanged. The data shows that SdD increased contractile tension in a
      concentration-dependent way, both on vascular and gastric smooth muscles. The
      vasoconstriction is unrelated to alpha(1), M, 5-HT(2A) and vanilloid receptors as
      well as L-type calcium channels. SdD increased also contraction by carbachol on
      rat gastric fundus. Thus for the first time, experimental data provides evidence
      that sap from C. lechleri owns constricting activity on smooth muscles.

PMID- 19406631
TI  - Health-related quality of life in outpatient women with COPD in daily practice:
      the MUVICE Spanish study.
AB  - AIMS: A cross-sectional multicenter study was designed to assess health-related
      quality of life (HRQL) in women with chronic obstructive pulmonary disease (COPD)
      who were attended in the outpatient setting in actual conditions of the daily
      practice. METHODS: A total of 1786 women with COPD (mean age of 66.5 years) and
      1661 pairs of men and women matched by age and COPD severity participated in a
      cross-sectional study. HRQL was measured with the Short Form 12 Health Survey
      Questionnaire (SF-12). RESULTS: The mean PCS-12 and MCS-12 scores were 36.5+/
      10.3 and 44.1+/-11.8, respectively. General health and physical functioning
      domains were those with the lowest scores, whereas role emotional and social
      functioning were those with the highest scores. The percentage of women with low
      HRQL increased according to age, whereas the percentage of women with high or
      normal HRQL decreased significantly. In relation to COPD severity, more women
      rated HRQL as low in the physical component than in the mental component. HRQL
      correlated significantly with FEV(1) in both PCS-12 and MCS-12 scales. As
      expected, an inverse significant correlation between HRQL and degree of dyspnea
      in the PCS-12 and the MCS-12 scales was observed. Women had also a significantly
      worse HRQL than men in all physical and mental domains. CONCLUSIONS: In
      outpatient women with COPD, HRQL was impaired especially the physical component
      of the SF-12. For the same age and severity of COPD, women showed significantly
      lower scores in all physical and mental domains of the SF-12 than men.

PMID- 19406632
TI  - The sequence-structure relationship and protein function prediction.
AB  - An incomplete understanding of protein sequence/structure/function relationships
      causes many difficulties for prediction methods. The highly complex nature of
      these relationships is a consequence of the interplay between physics and
      evolution that has been studied using a wide array of experimental and
      theoretical techniques. We review recent findings relating to conservation of
      sequence, structure and function and discuss their use in developing improved
      prediction methods.

PMID- 19406634
TI  - Two-stage anaerobic digestion of biodegradable municipal solid waste using a
      rotating drum mesh filter bioreactor and anaerobic filter.
AB  - A rotating drum mesh filter bioreactor (RDMFBR) with a 100 microm mesh coupled to
      an anaerobic filter was used for the anaerobic digestion of biodegradable
      municipal solid waste (BMW). Duplicate systems were operated for 72 days at an
      organic loading rate (OLR) of 7.5 g VS l(-1) d(-1). Early in the experiment most
      of the methane was produced in the 2nd stage. This situation gradually reversed
      as methanogenesis became established in the 1st stage digester, which eventually
      produced 86-87% of the total system methane. The total methane production was 0.2
      l g(-1) VS(added) with 60-62% volatile solids destruction. No fouling was
      experienced during the experiment at a transmembrane flux rate of 3.5 l m(-2) h(
      1). The system proved to be robust and stably adjusted to a shock loading
      increase to 15 g VS l(-1) d(-1), although this reduced the overall methane
      production to 0.15 l g(-1) VS(added).

PMID- 19406633
TI  - Angiogenesis in pre-malignant conditions.
AB  - Angiogenesis is an essential process involved in the normal growth and
      differentiation. In its defective and excessive form, angiogenesis is a crucial
      event in the progression of many human diseases. Excessive angiogenesis was
      largely investigated in psoriasis, arthritis, diabetic retinopathy and malignant
      tumours. Soon after the discovery of angiogenic factors and their inhibitors, the
      angiogenesis jumped from the experimental studies to clinical application. Tumour
      associated angiogenesis is nowadays considered as a priority in oncology based on
      numerous evidences that showed a significant reduction in tumour growth following
      anti-angiogenic therapy. However, few data are available on pre-malignant
      conditions. First evidences on angiogenesis in pre-malignant lesions came from
      the evaluation of microvessel density (MVD). MVD was found to be significantly
      increased in a relatively large spectrum of pre-malignant squamous cell lesions,
      such as in the oral mucosa, skin, uterine cervix, vulva and anal canal. For many
      of them, a correlation was found between MVD and the expression of vascular
      endothelial growth factor (VEGF). Based on these data, it was suggested that
      tumour angiogenesis is not necessarily a characteristic of invasive tumour, but
      may be an early event during tumourigenesis. Additional evidences came from pre
      malignant lesions of glandular epithelia, in which the angiogenic switch was
      demonstrated by the immunohistochemical expression of VEGF in gastric metaplasia
      and dysplasia, in atypical adenoma of the colon, atypical hyperplasia and
      carcinoma in situ of the breast and others. Actually, there are convincing
      evidences for an active angiogenesis in many cases with pre-malignant conditions,
      and this supports a more accurate evaluation of different chemopreventive agents.

PMID- 19406635
TI  - Electricity generation and modeling of microbial fuel cell from continuous beer
      brewery wastewater.
AB  - Electricity production and modeling of microbial fuel cell (MFC) from continuous
      beer brewery wastewater was studied in this paper. A single air-cathode MFC was
      constructed, carbon fiber was used as anode and diluted brewery wastewater
      (COD=626.58 mg/L) as substrate. The MFC displayed an open-circuit voltage of
      0.578 V and a maximum power density of 9.52 W/m(3) (264 mW/m(2)). Using the model
      based on polarization curve, various voltage losses were quantified. At current
      density of 1.79 A/m(2), reaction kinetic loss and mass transport loss both
      achieved to 0.248 V; while ohmic loss was 0.046 V. Results demonstrated that it
      was feasible and stable for producing bioelectricity from brewery wastewater;
      while the most important factors which influenced the performance of the MFC are
      reaction kinetic loss and mass transport loss.

PMID- 19406636
TI  - NO donors. Part 18: Bioactive metabolites of GTN and PETN--synthesis and
      vasorelaxant properties.
AB  - The vasodilators glyceryl trinitrate (GTN) and pentaerythrityl tetranitrate
      (PETN) are supposed to be degraded in vivo to the lower nitrates PETriN, PEDN,
      PEMN, 1,2-GDN, 1,3-GDN, 1-GMN, and 2-GMN. We synthesized these bioactive
      metabolites as reference compounds for pharmacokinetic studies. The use of HPLC
      methods for monitoring the stepwise reduction of PETN to lower nitrates and the
      syntheses of the glyceryl dinitrates proved advantageous. Furthermore, we
      measured the vasorelaxant properties of all metabolites by performing organ bath
      experiments with porcine pulmonary arteries. In general, the vasodilator potency
      increases with the number of nitrate moieties in the compound.

PMID- 19406637
TI  - Synthesis and biological evaluation of arylhydrazinocyanoacrylates and N-aryl
      pyrazolecarboxylates.
AB  - A series of arylhydrazino-substituted cyanoacrylates 3 and N-aryl
      pyrazolecarboxylates 6 were synthesized and their bioactivities were evaluated.
      Though compounds 3 were designed as herbicide, some of them showed fungicidal
      activity and anti-tumor activity. Some of the compounds 6 exhibited plant growth
      regulatory activity.

PMID- 19406638
TI  - Predictive models of Cannabinoid-1 receptor antagonists derived from diverse
      classes.
AB  - Chemical database design is an important consideration for screening processes in
      drug discovery. More specifically, classification of a diverse compound set
      deeply influences the validation and the predictive power of prediction model for
      the designing of novel compounds. In this work, we investigated the effect of the
      reasonable classification on the prediction model. We first collected the known
      Cannabinoid-1 receptor antagonists. Following this, we calculate the chemical
      descriptors in order to classify the collected compounds. Finally, we build two
      predictive models via the 3D-QSAR using different molecular alignment and the
      alignment independent Molecular Interaction Field models.

PMID- 19406639
TI  - Catalytic asymmetric synthesis of cyclic alpha-alkyl-amino acid derivatives
      having a tetrasubstituted alpha-carbon.
AB  - Catalytic asymmetric synthesis of various cyclic alpha-alkyl-amino acid
      derivatives having a tetrasubstituted alpha-carbon has been accomplished by the
      utilization of phase-transfer alkylation of alpha-alkyl-amino acid derivatives.

PMID- 19406640
TI  - Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine
      transition state mimetics.
AB  - Our first generation of hydroxyethylamine BACE-1 inhibitors proved unlikely to
      provide molecules that would lower amyloid in an animal model at low oral doses.
      This observation led us to the discovery of a second generation of inhibitors
      having nanomolar activity in a cell-based assay and with the potential for
      improved pharmacokinetic profiles. In this Letter, we describe our successful
      strategy for the optimization of oral bioavailability and also give insights into
      the design of compounds with the potential for improved brain penetration.

PMID- 19406641
TI  - Conformational analysis of N,N-disubstituted-1,4-diazepane orexin receptor
      antagonists and implications for receptor binding.
AB  - NMR spectroscopy, X-ray crystallography, and molecular modeling studies indicate
      that N,N-disubstituted-1,4-diazepane orexin receptor antagonists exist in an
      unexpected low-energy conformation that is characterized by an intramolecular pi
      stacking interaction and a twist-boat ring conformation. Synthesis and evaluation
      of a macrocycle that enforces a similar conformation suggest that this geometry
      mimics the bioactive conformation.

PMID- 19406642
TI  - New players in actin polymerization--WH2-domain-containing actin nucleators.
AB  - Actin nucleators promote the polymerization of the different types of actin
      arrays formed in a variety of cellular processes, such as cell migration,
      cellular morphogenesis and membrane trafficking processes. Several novel
      nucleators have been discovered recently. They all contain Wiskott-Aldrich
      syndrome protein (WASP) homology 2 (WH2 or W) domains for actin nucleation but
      seem to employ different molecular mechanisms and serve distinct cellular
      functions. Here, we summarize what is currently known about the different
      molecular mechanisms that Spire, Cordon-Bleu and Leiomodin seem to use and, also,
      the bacterial counterparts that mimic them (VopF, VopL and TARP). Recent studies
      on these WH2 proteins offer unique insight into the biological problem of actin
      filament formation and how cells use specialized molecular machines to bring
      about so many different cytoskeletal structures.

PMID- 19406644
TI  - What factors influence suboptimal ward care in the acutely ill ward patient?
AB  - As technological developments continue to offer patients more health care choices
      patient acuity increases. Patients that traditionally would have been cared for
      in a critical care environment are increasingly located on general wards. This
      change impacts on the acute care sector in a number of ways. Patients who are
      inpatients have more complex problems and a greater number of co-morbidities and
      are therefore more likely to suffer physiological deterioration. Procedures
      requiring inpatient stays are often more complex and associated with higher rates
      of mortality and morbidity. As patient acuity has increased research has
      highlighted that the care of the acutely ill ward patient is suboptimal.
      Suboptimal care implies a lack of knowledge regarding the significance of
      clinical findings relating to dysfunction of airway, breathing and circulation.
      This paper analyses the literature on the factors that contribute to suboptimal
      ward care of the acutely ill patient. It uses the categories proposed by
      McQuillan et al. [McQuillan P, Pilkington S, Allan A, Taylor B, Short A, Morgan
      G, et al. Confidential inquiry into quality of care before admission to intensive
      care. BMJ 1998;316(7148):1853-8] in relation to suboptimal ward care in an
      attempt to develop a conceptual analysis of the factors that influence suboptimal
      ward care and acutely ill ward patients. Thus, it aims to develop and enhance
      practitioners' knowledge and understanding of this topic and therefore improve
      patient care outcomes.

PMID- 19406643
TI  - Unconventional myosins acting unconventionally.
AB  - Unconventional myosins are proteins that bind actin filaments in an ATP-regulated
      manner. Because of their association with membranes, they have traditionally been
      viewed as motors that function primarily to transport membranous organelles along
      actin filaments. Recently, however, a wealth of roles for myosins that are not
      obviously related to organelle transport have been uncovered, including
      organization of F-actin, mitotic spindle regulation and gene transcription.
      Furthermore, it has also become apparent that the motor domains of different
      myosins vary strikingly in their biophysical attributes. We suggest that the
      assumption that most unconventional myosins function primarily as organelle
      transporters might be misguided.

PMID- 19406645
TI  - Preparation of novel (Z)-4-ylidenebenzo[b]furo[3,2-d][1,3]oxazines and their
      biological activity.
AB  - A reaction of 2-acetyl-3-acylaminobenzo[b]furans (9d-o) with Vilsmeier (VM)
      reagent afforded a mixture of (E)- and (Z)-{(E)-2-aralkenylbenzo[b]furo[3,2
      d][1,3]oxazin-4-ylidene}acetaldehydes (5) with a characteristic exo
      formylmethylene group on the oxazine ring. The Z-isomer was more stable than the
      E-isomer. The Z-isomers ((Z)-5) were reacted with phosphonate reagents under two
      different conditions to obtain various butadiene derivatives (12) containing
      benzo[b]furo[3,2-d][1,3]oxazine skeleton. Typical compounds (5 and 12) were
      evaluated for their anti-osteoclastic bone resorption activity, antagonistic
      activity for the cysLT1 receptor and growth inhibitory activity for MIA PaCa-2
      and MCF-7. Compounds 12f and 12j showed potent anti-osteoclastic bone resorption
      activity comparable to E(2) (17beta-estradiol).

PMID- 19406646
TI  - Convenient and highly effective fluorescence sensing for Hg2+ in aqueous solution
      and thin film.
AB  - A quinolinocyclodextrin, that is, MQAS-beta-cyclodextrin (MQAS = N-(2-methyl-8
      amino- quinolyl)-p-aminobenzene sulfonamide) was synthesized. Further experiments
      showed that it could form very stable stoichiometric 2:1 complex with Zn(2+) in
      water. Significantly, the resultant quinolinocyclodextrin/Zn(2+) complex showed
      the specific fluorescence response to Hg(2+) over other metal ions, which could
      be readily distinguished in either aqueous solution or the PVA-based thin film.
      This finding would enable Zn x 3(2) complex as a convenient and highly efficient
      fluorescence sensor for the detection of Hg(2+).

PMID- 19406647
TI  - Calculations of dose distributions in the lungs of a rat model irradiated in the
      thermal column of the TRIGA reactor in Pavia.
AB  - To test the possibility to apply boron neutron capture therapy (BNCT) to lung
      tumors, some rats are planned to be irradiated in the thermal column of the TRIGA
      reactor of the University of Pavia. Before the irradiation, lung metastases will
      be induced in BDIX rats, which will be subsequently infused with
      boronophenylalanine (BPA). During the irradiation, the rats will be positioned in
      a box designed to shield the whole animal except the thorax area. In order to
      optimize the irradiation set-up and to design a suitable shielding box, a set of
      calculations were performed with the MCNP Monte Carlo transport code. A rat model
      was constructed using the MCNP geometry capabilities and was positioned in a box
      with walls filled with lithium carbonate. A window was opened in front of the
      lung region. Different shapes of the holder and of the window were tested and
      analyzed in terms of the dose distribution obtained in the lungs and of the dose
      absorbed by the radiosensitive organs in the rat. The best configuration of the
      holder ensures an almost uniform thermal neutron flux inside the lungs
      (Phi(max)/Phi(min)=1.5), an irradiation time about 10 min long, to deliver at
      least 40 Gy(w) to the tumor, a mean lung dose of 5.9+/-0.4 Gy(w), and doses
      absorbed by all the other healthy tissues below the tolerance limits.

PMID- 19406648
TI  - T2 corrected quantification method of L-p-boronophenylalanine using proton
      magnetic resonance spectroscopy for boron neutron capture therapy.
AB  - In the present study, we aimed to evaluate a T2 corrected quantification method
      of l-p-boronophenylalanine (BPA) concentration using proton magnetic resonance
      spectroscopy (MRS). We used five phantoms containing BPA (1.5, 3.0, 5.0, 7.5, and
      10 mmol/kg=15, 30, 50, 75, and 100 microg(10)B/g), N-acetyl-aspartic acid (NAA:
      3.0 mmol/kg), creatine (Cr: 5.0 mmol/kg), and choline (Cho: 3.0 mmol/kg). The
      signal intensities of BPA and internal water were corrected by T2 relaxation
      time. The absolute concentrations of BPA were calculated by proton MRS using an
      internal water signal as a standard. The major BPA peaks were detected between
      7.1 and 7.6 ppm. Mean T2 relaxation time was 314.3+/-10.8 ms in BPA, 885.1+/-39.7
      ms in internal water. The calculated BPA concentrations were almost same as the
      actual concentration of BPA and the correlation coefficient was 0.99. Our BPA
      quantification method was very simple and non-invasive, also it had high
      accuracy. Therefore, our results indicate that proton MRS can be potentially
      useful technique for in vivo BPA quantification in boron neutron capture therapy
      (BNCT).

PMID- 19406649
TI  - Design of an accelerator-based neutron source for neutron capture therapy.
AB  - The boron neutron capture therapy is mainly suited in the treatment of some tumor
      kinds which revealed ineffective to the traditional radiotherapy. In order to
      take advantage of such a therapeutic modality in hospital environments, neutron
      beams of suitable energy and flux levels provided by compact size facilities are
      needed. The advantages and drawbacks of several neutron beams are here analysed
      in terms of therapeutic gains. In detail the GEANT-3/MICAP simulations show that
      high tumor control probability, with sub-lethal dose at healthy tissues, can be
      achieved by using neutron beams of few keV energy having a flux of about 10(9)
      neutrons/(cm(2)s). To produce such a neutron beam, the feasibility of a proton
      accelerator is investigated. In particular an appropriate choice of the
      radiofrequency parameters (modulation, efficiency of acceleration, phase shift,
      etc.) allows the development of relatively compact accelerators, having a proton
      beam current of 30 mA and an energy of 2 MeV, which could eventually lead to
      setting up of hospital-based neutron facilities.

PMID- 19406650
TI  - High power accelerator-based boron neutron capture with a liquid lithium target
      and new applications to treatment of infectious diseases.
AB  - A new conceptual design for an accelerator-based boron neutron capture therapy
      (ABNCT) facility based on the high-current low-energy proton beam driven by the
      linear accelerator at SARAF (Soreq Applied Research Accelerator Facility)
      incident on a windowless forced-flow liquid-lithium target, is described. The
      liquid-lithium target, currently in construction at Soreq NRC, will produce a
      neutron field suitable for the BNCT treatment of deep-seated tumor tissues,
      through the reaction (7)Li(p,n)(7)Be. The liquid-lithium target is designed to
      overcome the major problem of solid lithium targets, namely to sustain and
      dissipate the power deposited by the high-intensity proton beam. Together with
      diseases conventionally targeted by BNCT, we propose to study the application of
      our setup to a novel approach in treatment of diseases associated with bacterial
      infections and biofilms, e.g. inflammations on implants and prosthetic devices,
      cystic fibrosis, infectious kidney stones. Feasibility experiments evaluating the
      boron neutron capture effectiveness on bacteria annihilation are taking place at
      the Soreq nuclear reactor.

PMID- 19406651
TI  - New irradiation facility for biomedical applications at the RA-3 reactor thermal
      column.
AB  - A new irradiation facility has been developed in the RA-3 reactor in order to
      perform trials for the treatment of liver metastases using boron neutron capture
      therapy (BNCT). RA-3 is a production research reactor that works continuously
      five days a week. It had a thermal column with a small cross section access
      tunnel that was not accessible during operation. The objective of the work was to
      perform the necessary modifications to obtain a facility for irradiating a
      portion of the human liver. This irradiation facility must be operated without
      disrupting the normal reactor schedule and requires a highly thermalized neutron
      spectrum, a thermal flux of around 10(10) n cm(-2)s(-1) that is as isotropic and
      uniform as possible, as well as on-line instrumentation. The main modifications
      consist of enlarging the access tunnel inside the thermal column to the suitable
      dimensions, reducing the gamma dose rate at the irradiation position, and
      constructing properly shielded entrance gates enabled by logical control to
      safely irradiate and withdraw samples with the reactor at full power. Activation
      foils and a neutron shielded graphite ionization chamber were used for a
      preliminary in-air characterization of the irradiation site. The constructed
      facility is very practical and easy to use. Operational authorization was
      obtained from radioprotection personnel after confirming radiation levels did not
      significantly increase after the modification. A highly thermalized and
      homogenous irradiation field was obtained. Measurements in the empty cavity
      showed a thermal flux near 10(10) n cm(-2)s(-1), a cadmium ratio of 4100 for gold
      foils and a gamma dose rate of approximately 5 Gy h(-1).

PMID- 19406653
TI  - Comparative study of dose calculations with SERA and JCDS treatment planning
      systems.
AB  - Three treatment planning systems developed for clinical boron neutron capture
      therapy (BNCT) use are SERA developed by INL/Montana State University, NCTPlan
      developed by the Harvard-MIT and the CNEA group and JAEA computational dosimetry
      system (JCDS) developed by Japan Atomic Energy Agency (JAEA) in Japan.
      Previously, performance of the SERA and NCTPlan has been compared in various
      studies. In this preliminary study, the dose calculations performed with SERA and
      JCDS systems were compared in single brain cancer patient case with the FiR 1
      epithermal neutron beam. A two-field brain cancer treatment plan was performed
      with the both codes. The dose components to normal brain, tumor and planning
      target volume (PTV) were calculated and compared in case of one radiation field
      and combined two fields. The depth dose distributions and the maximum doses in
      regions of interest were compared. Calculations with the treatment planning
      systems for the thermal neutron induced ((10)B and nitrogen) dose components and
      photon dose were in good agreement. Higher discrepancy in the fast neutron dose
      calculations was found. In case of combined two-field treatment plan, overall
      discrepancy of the maximum weighted dose was approximately 3% for normal brain
      and PTV and approximately 4% for tumor dose.

PMID- 19406654
TI  - Development of boron nanocapsules for neutron capture therapy.
AB  - High accumulation and selective delivery of boron into tumor tissues are the most
      important requirements to achieve efficient neutron capture therapy of cancers.
      We focused on liposomal boron delivery system in order to achieve a large amount
      of boron delivery to tumor. We synthesized the double-tailed boron cluster lipid
      4c according to our reported procedure with modification. Size distribution of
      liposomes prepared from the boron cluster lipid 4c, DMPC, PEG-DSPE, and
      cholesterol was determined as 100 nm in diameter by an electrophoretic light
      scattering spectrophotometer. A high level of (10)B concentration (22 ppm) was
      observed in tumor tissue at 24 h after the administration of boron liposomes.

PMID- 19406652
TI  - Clinical results of BNCT for malignant brain tumors in children.
AB  - It is very difficult to treat the patients with malignant brain tumor in
      children, especially under 3 years, because the conventional irradiation cannot
      be applied due to the damage of normal brain tissue. However, boron neutron
      capture therapy (BNCT) has tumor selectivity such that it can make damage only in
      tumor cells. We evaluated the clinical results and courses in patients with
      malignant glioma under 15 years. Among 183 patients with brain tumors treated by
      our group using BSH-based intra-operative BNCT, 23 patients were under 15 years.
      They included 4 patients under 3 years. There were 3 glioblastomas (GBM), 6
      anaplastic astrocytomas(AAS), 7 primitive neuroectodermal tumors (PNET), 6
      pontine gliomas and 1 anaplastic ependymoma. All GBM and PNET patients died due
      to CSF and/or CNS dissemination without local tumor regrowth. All pontine glioma
      patients died due to regrowth of the tumor. Four of 6 anaplastic astrocytoma and
      1 anaplastic ependymoma patients alive without tumor recurrence. BNCT can be
      applied to malignant brain tumors in children, especially under 3 years instead
      of conventional radiation. Although it can achieve the local control in the
      primary site, it cannot prevent CSF dissemination in patients with glioblastoma.

PMID- 19406655
TI  - Differential regulation of SERK, LEC1-like and pathogenesis-related genes during
      indirect secondary somatic embryogenesis in grapevine.
AB  - A culture model was developed in Vitis vinifera L., cultivar 'Chardonnay' for
      studying SE (Somatic Embryogenesis). The auxin 2,4-D (2,4-Dichlorophenoxyacetic
      acid) was used to induce indirect secondary embryogenesis at a high rate,
      starting from embryos derived from embryogenic cultures previously obtained.
      Cotyledonary embryos were shown to be more responsive to SE induction than
      embryos at the torpedo-stage and were used for molecular analyses. The expression
      of SERK (Somatic Embryogenesis Receptor Kinase), L1L (Leafy Cotyledon1 Like) and
      a set of PR (Pathogenesis-Related) genes was monitored during the whole SE
      process. VvSERK1, VvSERK2 and VvL1L were down-regulated by the 2,4-D treatment
      but expressed in embryonic tissues. On the contrary, VvPR1, VvPR8, VvPR10.1 and
      VvPR10.3 were strongly up-regulated by the 2,4-D treatment, and their transcripts
      were not or only weakly detected in clusters of secondary embryos. VvSERK3, VvPR3
      and VvPR10.2 were more stably expressed in all tissues examined. The discussion
      deals with the putative role of the different genes in grapevine SE.

PMID- 19406656
TI  - Surgical repair of coronary artery to pulmonary artery fistula with aneurysms.
AB  - A 58-year-old female was referred to our hospital with an abnormal shadow on her
      chest X-ray. Further examination revealed the left anterior descending coronary
      artery to pulmonary artery fistula with aneurysms. The patient was successfully
      repaired with operation and had no residual fistulas and aneurysms.

PMID- 19406657
TI  - Median sternotomy for combined coronary artery bypass grafting and lung tumor
      resection: is it valid or not?

PMID- 19406658
TI  - The effect of fenoldopam and dopexamine on hepatic blood flow and hepatic
      function following coronary artery bypass grafting with hypothermic
      cardiopulmonary bypass.
AB  - BACKGROUND: Hypothermic cardiopulmonary bypass is associated with low perfusion
      state causing a mismatch between demand and supply to various organs such as gut,
      kidneys and brain. The consequences are thought to be responsible for
      postoperative complications like systemic inflammatory response, renal failure,
      neurological injury, etc. Pharmacological agents like dopamine, dopexamine and
      dobutamine have been used in an attempt to reduce hypoperfusion and hence
      complications. Fenoldopam, a dopamine analog (DA-1 receptor agonist), has
      recently been shown to be specific reno-splanchnic vasodilator in animal studies.
      We studied the haemodynamic effects of fenoldopam and its effect on hepatic blood
      flow (HBF) during and after cardiopulmonary bypass and compared these with
      dopexamine. METHODS: Ethics committee approval was obtained. Forty-two
      consecutive patients with good/moderate left ventricular function undergoing
      either elective/urgent coronary artery bypass grafting were included in the
      study. Patients were randomised to receive either fenoldopam (0.2 microg/kgmin)
      (F; n=14) or dopexamine (2.0 microg/kgmin) (Dx; n=14) normal saline (NS; n=14)
      continuously after induction of anaesthesia for 24h following completion of
      surgery. HBF was measured using the Indocyanine green dye disappearance rate
      method, before, during and after cardiopulmonary bypass. Data were collected pre
      , intra- and postoperatively. Serum liver enzymes were measured during the
      perioperative period. Repeated measures ANOVA test was used to compare timed
      samples in both groups. RESULTS: The study groups were comparable in pre- and
      intraoperative variables. In the fenoldopam and dopexamine groups there was a
      significant increase in heart rate 15 min following the commencement of the
      infusion (NS:F:DX::-2.0+/-7.8 beats/min:13.6+/-8.1 beats/min (p=0.007):18.36+/
      20.2 beats/min (p=0.004)). However the change in mean arterial blood pressure was
      similar (NS:F:DX::-12.7+/-14.9:-4.0+/-23.1 (p=0.699):-2.6+/-22.3) (p=0.235).
      Cardiac index increased and systemic vascular resistance decreased (requiring
      noradrenaline infusion) in the fenoldopam group, however this did not reach
      statistical significance. Hepatic blood flow reduced during CPB and returned to
      near preoperative levels in all three groups with no statistical difference
      between groups. CONCLUSIONS: Fenoldopam infusion induced transient tachycardia,
      with no augmentation of hepatic blood flow whereas dopexamine induced tachycardia
      and did not augment hepatic blood flow. Fenoldopam and dopexamine may have hepato
      protective effect.

PMID- 19406659
TI  - Photodynamic therapy (PDT): a short review on cellular mechanisms and cancer
      research applications for PDT.
AB  - Photodynamic therapy (PDT) has been used for many years, but it is only now
      becoming widely accepted and utilized. Originally it was developed as a tumor
      therapy and some of its most successful applications are for non-malignant
      diseases. This article provides a broad review of different parameters used and
      mechanisms instituted in PDT such as photosensitizers (PS), photochemistry and
      photophysics, cellular localization, cellular signaling, cell metabolism and
      modes of cell death that operate on a cellular level, as well as photosensitizer
      pharmacokinetics, biodistribution, tumor localization and modes of tumor
      destruction. These specific cellular mechanisms are most commonly applied in PDT
      and for the most part are often researched and exploited. If the combination of
      these specific parameters and mechanisms can be optimized within PDT it could
      possibly be used as a suitable alternative for the treatment and management of
      specific cancers.

PMID- 19406661
TI  - The spiritual dimension of cancer care.
AB  - Spirituality is more about constant questioning than about providing fixed or
      final answers. Cancer patients do not expect spiritual solutions from oncology
      team members, but they wish to feel comfortable enough to raise spiritual issues
      and not be met with fear, judgmental attitudes, or dismissive comments. Spiritual
      needs may not be explicit in all illness phases, yet spirituality is not only
      confined to the areas of palliative or end-of-life care. Sensitive and effective
      methods to assess and address spiritual needs of cancer patients are being
      developed and qualitative research on the topic is underway. In addition, formal
      education and training in communication about cancer patients' spiritual issues
      and in how to assess and address them in the clinical context is being
      increasingly provided. Spirituality can be a major resource for both patients and
      physicians, yet it can never be imposed but only shared. Those oncology
      professionals who are familiar with their own spirituality will be better at
      recognizing, understanding and attending to their patients' spiritual needs and
      concerns.

PMID- 19406662
TI  - Pathogenic bacteria and TNF do not induce production of macrophage migration
      inhibitory factor (MIF) by human monocytes.
AB  - Elevated serum macrophage migration inhibitory factor (MIF) is associated with
      severe sepsis, but it is not clear whether bacteria stimulate synthesis of MIF by
      blood leukocytes directly or via induction of TNF. Here we assess production of
      MIF mRNA and protein by blood leukocytes from healthy human subjects (n=28)
      following exposure to bacteria commonly associated with sepsis (Escherichia coli
      and Streptococcus pneumoniae). Bacteria did not increase levels of MIF mRNA or
      secreted protein. CD14(+) monocytes were the main cell type producing MIF before
      and after stimulation. Exposure of leukocytes to TNF did not induce MIF. Hence
      elevated levels of serum MIF observed in sepsis may not reflect MIF produced by
      blood leukocytes stimulated directly by bacteria or TNF.

PMID- 19406660
TI  - Incidence and clinical impact of chemotherapy induced myelotoxicity in cancer
      patients: an observational retrospective survey.
AB  - PURPOSE: To evaluate the frequency of chemotherapy-induced myelotoxicity in
      cancer patients, the related treatment (G-CSF, rHuEPO), and the occurrence of
      chemotherapy dose reductions, delays or discontinuations. PATIENTS AND METHODS:
      We retrospectively collected data from 1175 patients who completed at least four
      chemotherapy courses at 64 Italian Centres. Myelotoxicity was defined as anemia
      (Hb < 10 g/dL) and neutropenia (ANC < 1500/mm(3)). The study population was
      divided by age, in 664 adult patients aged < or =65 years and 511 elderly
      patients, aged > 65 years. The association between events during chemotherapy and
      myelotoxicity indices were assessed by logistic regression. RESULTS: The median
      age of the patients was 64 years. Myelotoxicity was observed in 633 patients
      (53.9%), anemia (< 10 g/dL) in 263 (22.4%) and neutropenia in 530 (45.1%); 686
      patients (58.5%) showed mild anemia (Hb < 12 g/dL). Dose reductions were observed
      in 199 patients (16.9%), dose delays in 338 (28.7%), and discontinuations in 157
      (13.4%), with no significant difference between age groups. Myelotoxicity
      accounted for 20% of treatment withdrawals with no differences between age
      groups. G-CSF was administered to 53.4% of the neutropenic patients, and rHuEPO
      to 53.1% of the anemic patients. Logistic regression analyses showed a
      significant (P < 0.001) association between chemotherapy dose delays, dose
      reductions and myelotoxicity. Considering age strata, the association between
      dose reduction and myelotoxicity was significant. The risk of neutropenia in the
      adults was higher than in elderly (50.0% vs 38.7%). CONCLUSION: Our results show
      that anemia and neutropenia occur in a substantial proportion of cancer patients
      receiving chemotherapy, and have an impact on chemotherapy dose delivery. G-CSF
      and rHuEPO are treatments widely used in about one half of neutropenic and anemic
      patients. Particular attention should be given to elderly patients, who are at
      high risk of myelotoxicity and should be carefully evaluated for the prophylactic
      use of G-CSF and monitored for the appropriate use of rHuEPO.

PMID- 19406663
TI  - Cadmium exposure is associated with elevated blood C-reactive protein and
      fibrinogen in the U. S. population: the third national health and nutrition
      examination survey (NHANES III, 1988-1994).
AB  - PURPOSE: Epidemiologic data suggest an association between cadmium exposure and
      cardiovascular disease though the underlying mechanisms remain unclear. This
      study explored the hypothesis that cadmium exposure is associated with elevated C
      reactive protein (CRP) and fibrinogen, two risk factors for developing
      cardiovascular disease. METHODS: The current study investigated associations
      between urinary cadmium and the prevalence of elevated blood CRP (> or = 2.2
      mg/L) and fibrinogen (> or = 10.35 micromol/L) using data from a sample of 6497
      participants aged 40-79 in the Third National Health and Nutrition Examination
      Survey. Logistic regression model was used to investigate existing associations
      while adjusting for confounding variables. RESULTS: Both simple and covariate
      adjusted models indicated that urinary cadmium was associated with elevated CRP
      and fibrinogen in a dose-dependent fashion (p(trend)<0.05 for both). Adjusted
      odds ratios for increased CRP and fibrinogen comparing highest with lowest
      quartiles of urinary cadmium were 1.62 (95% confidence interval [CI], 1.24-2.12)
      and 2.12 (1.43-3.14), respectively. CONCLUSIONS: This analysis shows that cadmium
      exposure is associated with high prevalence of elevated CRP and fibrinogen.
      Additional study will be required to determine whether the increased risk derives
      from cadmium per se or from the environmental circumstances responsible for
      acquiring the contamination, e.g., cigarette smoking.

PMID- 19406665
TI  - Scapulothoracic motion and muscle activity during the raising and lowering phases
      of an overhead reaching task.
AB  - Scapulothoracic muscle activity is essential for normal scapulothoracic motion.
      While previous research has furthered the understanding of scapulothoracic motion
      and muscle activity during the raising phase of motion, a gap exists with respect
      to the lowering phase. The purpose of this study was to compare scapulothoracic
      motion and scapulothoracic muscle activity between the raising and lowering
      phases of an overhead reaching task. Twenty healthy subjects volunteered to
      participate in the study. Three-dimensional scapulothoracic motion was collected
      using an electromagnetic device. Surface electromyography (EMG) was used to
      assess muscle activity from the upper trapezius, lower trapezius, and serratus
      anterior muscles. Overall scapulothoracic motion was similar for the raising and
      lowering phases of the overhead reaching task. However, significantly lower EMG
      amplitude values existed during the lowering phase across all muscles. Less
      muscle activity during the lowering phase may reflect differing neuromuscular
      control strategies between arm raising and lowering. These findings suggest that
      scapulothoracic muscle activation levels during eccentric contractions may be
      closer to an activation threshold below which their ability to control
      scapulothoracic motion may be compromised subsequently leading to altered
      scapulothoracic motion (scapular dyskinesis). This provides a possible
      explanation for why scapular dyskinesis is more notable during the lowering phase
      of motion.

PMID- 19406664
TI  - EMG spectral indices and muscle power fatigue during dynamic contractions.
AB  - The purpose of this study was to examine acute exercise-induced changes on muscle
      power output and surface electromyography (sEMG) parameters (amplitude and
      spectral indices of muscle fatigue) during a dynamic fatiguing protocol. Fifteen
      trained subjects performed five sets consisting of 10 leg presses (10RM), with
      2min rest between sets. Surface electromyography was recorded from vastus
      medialis (VM) and lateralis (VL) and biceps femoris (BF) muscles. A number of EMG
      based parameters were compared for estimation accuracy and sensitivity to detect
      peripheral muscle fatigue. These were: Mean Average Voltage, median spectral
      frequency, Dimitrov spectral index of muscle fatigue (FI(nsm5)), as well as other
      parameters obtained from a time-frequency analysis (Choi-Williams distributions)
      such as mean and variance of the instantaneous frequency and frequency variance.
      The log FI(nsm5) as a single parameter predictor accounted for 37% of the
      performance variance of changes in muscle power and the log FI(nsm5) and MFM as a
      two factor combination predictor accounted for 44%. Peripheral impairments
      assessed by sEMG spectral index FI(nsm5) may be a relevant factor involved in the
      loss of power output after dynamic high-loading fatiguing task.

PMID- 19406666
TI  - Computational modeling of blood flow in the TrapEase inferior vena cava filter.
AB  - PURPOSE: To evaluate the hemodynamics of the TrapEase vena cava filter (Cordis,
      Miami Lakes, Florida) by using three-dimensional computational fluid dynamics,
      including simulated thrombi of multiple shapes, sizes, and trapping positions.
      The study was performed to identify areas of stagnant and/or recirculating flow
      that may have an effect on intrafilter thrombosis. MATERIALS AND METHODS: Three
      dimensional computer models of the TrapEase filter, various thrombi shapes and
      sizes, and a 23-mm-diameter cava were constructed. The hemodynamics of steady
      state flow were examined for the unoccluded and partially occluded filter.
      RESULTS: Flow in the unoccluded TrapEase filter experienced minimal disruption.
      Spherical thrombi in the downstream trapping position induced stagnant and/or
      recirculating flow downstream of the thrombus. The volume of stagnant flow and
      the peak wall shear stress increased with thrombus volume. For spherical thrombi
      trapped upstream, disruption of flow was observed along the cava wall ipsilateral
      to the thrombus and within the filter. Peak wall shear stress was greatest with
      conical thrombi, less with spherical thrombi, and least with ellipsoidal thrombi.
      CONCLUSIONS: The authors have designed a computer model to study the hemodynamics
      of the TrapEase filter with various thrombi and trapping positions. The model
      offers advantages over in vitro techniques, specifically improved resolution and
      easy adaptation for new filter designs, thrombus morphologies and/or sizes, and
      flow parameters. The results agree with those of previous bench experiments that
      suggest the upstream trapping position of the TrapEase filter leads to a
      potentially thrombogenic region of stagnant and/or recirculating flow with low
      shear stress. These findings are supported by clinical studies showing an
      increased incidence of occlusive and/or nonocclusive thrombus within the TrapEase
      filter and the retrievable, nearly structurally identical, OptEase filter.

PMID- 19406667
TI  - Bronchial artery embolization for the management of hemoptysis in oncology
      patients: utility and prognostic factors.
AB  - PURPOSE: To evaluate the utility of bronchial artery embolization (BAE) in the
      oncology population and determine prognostic factors. MATERIALS AND METHODS: This
      is a retrospective review of 30 consecutive oncology patients (20 men, 10 women;
      mean age, 60 years) who were referred for BAE for the management of hemoptysis
      from 1992 to 2007. RESULTS: The amount of hemoptysis at initial embolization was
      massive (frank blood >300 mL per 24 hours) in 13 patients (43%), moderate (frank
      blood <300 mL per 24 hours) in 15 (50%), and trivial (blood-tinged sputum) in two
      (7%). Eighteen patients (60%) had a primary intrathoracic malignancy, seven (23%)
      had pulmonary metastases, and five (17%) had no evidence of malignant disease in
      the lung. The technical success rate, defined as the ability to selectively
      embolize the abnormal vessel, was 86% (32 of 37 procedures). Clinical response
      categories and complications were defined according to the guidelines established
      by the SIR Standards of Practice Committee. The major complication rate was 3%,
      including one case of spinal cord infarction. BAE provided symptom palliation
      with an immediate decrease or resolution of bleeding in 24 out of 27 patients
      (89%). The 30-day mortality rate for this cohort was 30%, and the median survival
      was 5.5 months. Survival was significantly better in patients with non-tumor
      related hemoptysis than in those with tumor-related bleeding (P = .004). There
      was no significant difference in median survival between patients with massive
      hemoptysis and those with moderate/mild hemoptysis (P = .81), between patients
      with an emergent procedure and those with a non-emergent procedure (P = .39), and
      between patients who had previously undergone radiation therapy and those who had
      not (P = .4). CONCLUSIONS: BAE is safe and effective for the oncologic patient
      population. In patients with tumor-related hemoptysis, the prognosis remains
      poor; however, for the subset of oncology patients whose hemoptysis is not
      related to malignant disease in the lung, the survival is significantly better.

PMID- 19406668
TI  - Radiation dermatitis following radioembolization for hepatocellular carcinoma: a
      case for prophylactic embolization of a patent falciform artery.
AB  - The most common use of radioembolization is in the treatment of primary and
      secondary liver tumors, and the most common radioisotope used is yttrium-90. This
      form of therapy has been proven to be successful in achieving tumor reduction and
      prolonging survival. Adverse events, although uncommon and usually self-limiting,
      have been reported. The present report describes a case of radiation dermatitis
      caused by shunting of (90)Y microspheres to the anterior abdominal wall via a
      patent falciform artery. When identified, prophylactic embolization of this
      patent artery may prevent the potential adverse event of radiation-induced
      dermatitis after radioembolization.

PMID- 19406669
TI  - Covered stent to treat pulmonary arteriovenous malformation with short feeding
      artery.
AB  - A patient with hereditary hemorrhagic telangiectasia and multiple bilateral
      pulmonary arteriovenous malformations (PAVMs) was found to have a complex PAVM in
      the left upper lobe with two feeder vessels, one of which could be successfully
      embolized with coils but the other of which was extremely short. Preservation of
      the parent vessel was considered important as it supplied a large portion of the
      left upper lobe. A covered stent was used to successfully exclude the feeding
      vessel and treat the PAVM. At 6-month follow-up, the PAVM sac was gone and the
      stent remained patent.

PMID- 19406670
TI  - Aortic and vertebral penetration by a G2 inferior vena cava filter: report of a
      case.
AB  - Various long-term complications have been reported with inferior vena cava
      filters. In this report, the authors describe unusual complications associated
      with a G2 filter in a patient with aortic lumen and vertebral body penetration.

PMID- 19406671
TI  - Emergency endovascular treatment for ruptured type B dissection in the abdominal
      aorta.
AB  - Despite successful endograft placement in the thoracic aorta, dissections remain
      problematic in the abdominal aorta. Herein, the authors describe two successful
      cases of endovascular treatment of ruptured abdominal aortic dissections. One
      patient, despite previously undergoing successful thoracic endograft placement,
      presented with a ruptured false channel and was treated by excluding major re
      entries with a covered renal stent and stent-graft limb. A second patient, with a
      ruptured dissection superimposed on a preexisting abdominal aortic aneurysm, was
      treated with thoracic and abdominal stent-grafts. In both patients, progressive
      healing of the aorta occurred, with patients presenting no symptoms at an average
      follow-up of 20 months.

PMID- 19406672
TI  - Large persistent ductus venosus: retrograde transvenous embolization with a
      double-catheter technique.

PMID- 19406673
TI  - Measurement of visual strain in radiologists.
AB  - RATIONALE AND OBJECTIVES: The authors hypothesized that the current practice of
      radiology produces oculomotor fatigue that reduces diagnostic accuracy. MATERIALS
      AND METHODS: Testing this hypothesis required an ability to measure eyestrain.
      This capability was developed by measuring the visual accommodation of
      radiologists before and after diagnostic viewing work using an autorefractor that
      was capable of making multiple measurements of accommodation per second. Three
      radiologists and three residents focused on a simple target placed at near to far
      distances while accommodation was measured. The target distances varied from 20
      to 183 cm from the eye. The data were collected prior to and after a day of
      digital diagnostic viewing. RESULTS: The results indicated that accommodation at
      near distances was significantly worse overall compared to far distances and was
      significantly worse after a day of digital reading at all distances. CONCLUSIONS:
      Because diagnostic image interpretation is performed at near viewing distances,
      this inability to maintain focus on an image could affect diagnostic accuracy. As
      expected, younger residents had better accommodative accuracy than older
      radiologists.

PMID- 19406674
TI  - Neurobiological approaches on brains of children with dyslexia: review.
AB  - Learning difficulties commonly comprise a heterogeneous group of disorders
      manifested by unexpected problems in some children's experiences in the academic
      performance arena. These problems especially comprise of a variety of disorders,
      which one of the most well-recognized learning difficulties is reading disability
      or dyslexia. The aim of this review is to explain the postmortem, structural or
      functional neuroimaging, and electrophysiological studies of human brains in
      children. The findings about these neuropathological and neurofunctional
      characteristics of developmental dyslexia, prospective studies beginning early in
      the life span and studies targeting remedial intervention will help to set the
      research agendas for future studies to follow.

PMID- 19406675
TI  - Introduction. Equitation Science.

PMID- 19406676
TI  - Impedance matching with an adjustable segmented transmission line.
AB  - A capability for impedance matching between the RF probe and the spectrometer is
      a standard requirement for NMR. Both lumped element and branched transmission
      line methods are widely used for this purpose. Here, we propose to use the
      segmented transmission line structure which is well known in wireless
      communications. It relies upon reflections between transmission lines of
      different characteristic impedances that are serially connected to match the
      impedance of a coil or resonator to the characteristic impedance of the NMR
      spectrometer. In our implementation, two quarter wave length dielectric slugs are
      placed within a coaxial transmission line. Adjustment of the positions of the
      slugs allows the variable tuning and matching needed for NMR probes, eliminating
      the need for variable capacitors and inductors. As a demonstration of the
      usefulness of this approach, we have incorporated a variable segmented
      transmission line into a home-built Variable Angle Spinning probe. Finally, we
      discuss the range of possible application for segmented transmission line
      networks in NMR probe design.

PMID- 19406677
TI  - Tunnelling magnetic resonances: dynamic nuclear polarisation and the diffusion of
      methyl group tunnelling energy.
AB  - The dynamic nuclear polarisation (DNP) of (1)H spins arising from methyl
      tunnelling magnetic resonances has been investigated in copper-doped zinc acetate
      dihydrate using field-cycling NMR spectroscopy at 4.2K. The tunnel resonances
      appear in the field range 20-50 mT and trace out the envelope of the electron
      spin resonance spectrum of the Cu(2+) ion impurities. By investigating the DNP
      line shapes as a function of time, the cooling of the methyl tunnel reservoir has
      been probed. The role of spectral diffusion of tunnelling energy in determining
      the DNP line shapes has been investigated through experiments and numerical
      simulations based on a theoretical model that describes the time evolution of the
      (1)H polarisation and the tunnelling temperature. The model is discussed in
      detail in comparison with the experiments. All effects have been studied as a
      function of Cu(2+) ion concentration.

PMID- 19406678
TI  - Optical detection of NMR J-spectra at zero magnetic field.
AB  - Scalar couplings of the form JI(1) x I(2) between nuclei impart valuable
      information about molecular structure to nuclear magnetic-resonance spectra. Here
      we demonstrate direct detection of J-spectra due to both heteronuclear and
      homonuclear J-coupling in a zero-field environment where the Zeeman interaction
      is completely absent. We show that characteristic functional groups exhibit
      distinct spectra with straightforward interpretation for chemical identification.
      Detection is performed with a microfabricated optical atomic magnetometer,
      providing high sensitivity to samples of microliter volumes. We obtain 0.1 Hz
      linewidths and measure scalar-coupling parameters with 4-mHz statistical
      uncertainty. We anticipate that the technique described here will provide a new
      modality for high-precision "J spectroscopy" using small samples on microchip
      devices for multiplexed screening, assaying, and sample identification in
      chemistry and biomedicine.

PMID- 19406680
TI  - Ultrasound-assisted extraction coupled with under vacuum distillation of flavour
      compounds from spearmint (carvone-rich) plants: Comparison with conventional
      hydrodistillation.
AB  - Ultrasonically assisted extraction of flavour compounds from different varieties
      of Mentha spicata, using 70% ethanol, have been carried out for 5, 10 and 15min
      and coupled with under vacuum distillation. The ultrasound distilled extracts
      have been analysed by GC-MS and compared with essential oils obtained by
      hydrodistillation. The results have showed that ultrasonically assisted
      extraction in combination with under vacuum distillation have provided extracts
      with higher flavouring strength due to the increased concentration of desirable
      oxygenated compounds (from 5 to 8 times) compared with hydrodistillation.
      Extraction yields of flavour volatiles have been calculated giving a range 0.04
      0.13% by ultrasound and 0.01-0.02% by hydrodistillation.

PMID- 19406679
TI  - Reduced susceptibility to azoxymethane-induced aberrant crypt foci formation and
      colon cancer in growth hormone deficient rats.
AB  - OBJECTIVES: To evaluate the role of GH in colon carcinogenesis, we examined the
      formation of aberrant crypt foci (ACFs) and tumor development in wild type (WT)
      and GH-deficient, spontaneous dwarf rats (SDRs) exposed to the carcinogen
      azoxymethane (AOM). DESIGN: ACF were quantified by stereomicroscopy and tumor
      number and weights were recorded for each animal. Cell proliferation was measured
      by vincristine metaphase arrest, flow cytometry, and bromodeoxyuridine (BrdU)
      incorporation. Apoptosis was measured by TUNEL staining and cleaved caspase-3
      immunohistochemistry. IGF-I was measured by radioimmunoassay (RIA). Hexokinase
      activity was measured by spectrophotometric assay. PARP cleavage, and IGF-IR, and
      p27(kip/cip) expression were measured by Western blotting. RESULTS: ACFs detected
      by stereomicroscopy were markedly reduced ( approximately 85%) in SDRs vs. WT
      rats at 10, 25, and 28 weeks after AOM. Tumor incidence, number, and weight also
      were reduced in SDR vs. WT animals. AOM treatment increased cell proliferation in
      the distal colon (where tumors occur) of WT rats but not SDRs, and these changes
      corresponded to increased ACF and tumor formation. Apoptosis rates were similar
      in AOM-treated WT and SDRs. Alterations in serum IGF-I levels may contribute to
      differences in the proliferative response to AOM and decreased ACF formation in
      SDR vs. WT rats. CONCLUSIONS: We conclude that early neoplastic lesions (ACFs)
      were reduced in GH-deficient animals. This effect corresponds with differences in
      AOM-induced proliferation, but not apoptosis. These data indicate that GH is
      required for the full effect of AOM on colon ACF and tumor development, and that
      the SDR rat is a promising model for studies regarding the role of GH/IGF system
      in the initiation and promotion of colon cancer.

PMID- 19406681
TI  - Involvement of cardiac sympathetic nerve endings in a patient with idiopathic RBD
      and intact nigrostriatal pathway.

PMID- 19406682
TI  - Does the built environment relate to the metabolic syndrome in adolescents?
AB  - This article examines the influence of the neighborhood environment on blood
      profiles, percent body fat, blood pressure, and the metabolic syndrome (MetS) in
      adolescents. One hundred and eighty-eight adolescents (10-16 yr) agreed to have a
      fasting blood sample drawn in addition to measures of weight, height, percent
      fat, and blood pressure. A MetS cluster score was derived by calculating the sum
      of the sample-specific z-scores from the percent body fat, fasting glucose, high
      density lipoprotein cholesterol (negative), triglyceride, and systolic blood
      pressure. Geographic Information Systems (GIS) technology was used to calculate
      the distance to and density of built environmental features. Spearman correlation
      was used to identify significant (p<0.05) relationships between the built
      environment and the MetS. Statistically significant correlations were added to
      linear regression models, adjusted for pubertal status, age, and sex.
      Multivariate linear regression models revealed significant associations between
      an increased distance to convenience stores and the MetS. The results of this
      study suggest a role for the built environment in the development of the MetS.

PMID- 19406685
TI  - DFT simulations and vibrational analysis of FT-IR and FT-Raman spectra of 2,4
      diamino-6-hydroxypyrimidine.
AB  - Quantum mechanical calculations of energies, geometries and vibrational
      wavenumbers of 2,4-diamino-6-hydroxypyrimidine (2,4DA6HP) were carried out by
      using ab initio HF and density functional theory (DFT/B3LYP) method using 6
      311G(d,p) basis set. The optimized geometrical parameters obtained by B3LYP
      method show good agreement with experimental X-ray data. The best level of theory
      in order to reproduce the experimental wavenumbers is B3LYP method with the 6
      311G(d,p) basis set. The difference between the observed and scaled wavenumber
      values of most of the fundamentals is very small. A detailed interpretation of
      the infrared spectra of 2,4DA6HP was also reported. The calculated HOMO and LUMO
      energies show that charge transfer occurs in the molecule. The entropy of the
      title compound is also performed at HF/6-311G(d,p) and B3LYP/6-311G(d,p) levels
      of theory. The theoretical spectrograms for FT-IR and FT-Raman spectra of the
      title molecule have been constructed.

PMID- 19406684
TI  - Is the autophagy machinery an executioner of programmed cell death in plants?

PMID- 19406686
TI  - Experimental and theoretical studies on 4-(2,4
      dichlorobenzylideneamino)antipyrine and 4-(2,6
      dichlorobenzylideneamino)antipyrine.
AB  - Two antipyrine derivates, with the same formula C(18)H(15)Cl(2)N(3)O, are
      structurally similar Schiff bases derived from the condensation of 2,4
      dichlorobenzaldehyde or 2,6-dichlorobenzaldehyde and 4-aminoantipyrine in
      methanol solutions. The compounds were characterized by elemental analysis, FT
      IR, FT-Raman and UV-vis techniques. Density functional calculations were
      performed to further optimize and characterize them. The calculated results
      indicate that the theoretical values show good agreements with experimental ones.
      They are similar in their IR spectra and different in their Raman spectra. The
      detailed vibrational and UV-vis absorption spectra of the compounds have been
      ascribed to their corresponding molecular structures and electrons orbital
      transitions. The statistical thermodynamic functions and their correlations with
      temperatures of the title compounds have been obtained from their theoretical
      vibrations of the optimized structures. The nonlinear optical and UV-vis
      properties indicate that the compounds are the promising photoelectronic
      materials.

PMID- 19406687
TI  - Cold oxygen plasma technology efficiency against different airborne respiratory
      viruses.
AB  - BACKGROUND: Respiratory infections caused by viruses are major causes of upper
      and lower respiratory tract infections. They account for an important mortality
      and morbidity worldwide. Amongst these viruses, influenza viruses and
      paramyxoviruses are major pathogens. Their transmission is mainly airborne, by
      direct transmission through droplets from infected cases. OBJECTIVES: In the
      context of an influenza pandemic, as well as for the reduction of nosocomial
      infections, systems that can reduce or control virus transmission will reduce the
      burden of this disease. It may also be part of the strategy for pandemic
      mitigation. STUDY DESIGN: A new system based on physical decontamination of
      surface and air has been developed. This process generates cold oxygen plasma
      (COP) by subjecting air to high-energy deep-UV light. To test its efficiency, we
      have developed an experimental device to assess for the decontamination of
      nebulized respiratory viruses. High titer suspensions of influenza virus type A,
      human parainfluenza virus type 3 and RSV have been tested. RESULTS: Different
      experimental conditions have been evaluated against these viruses. The use of COP
      with an internal device allowed the best results against all viruses tested. We
      recorded a reduction of 6.5, 3.8 and 4 log(10) TCID50/mL of the titre of the hPIV
      3, RSV and influenza virus A (H5N2) suspensions. CONCLUSIONS: The COP technology
      is an efficient and innovative strategy to control airborne virus dissemination.
      It could successfully control nosocomial diffusion of respiratory viruses in
      hospital setting, and could be useful for the reduction of influenza transmission
      in the various consultation settings implemented for the management of cases
      during a pandemic.

PMID- 19406688
TI  - Application of special techniques.

PMID- 19406690
TI  - Proposal of a formal gynecologic endoscopy curriculum.
AB  - As minimally invasive surgery becomes the standard of care in the United States
      and around the world, the formal training of endoscopic surgeons is an issue of
      growing concern. With the implementation of the American Association of
      Gynecologic Laparoscopists/Society of Reproductive Surgeons (AAGL/SRS)-sponsored
      fellowship training in gynecologic endoscopy and a growing number of hands-on
      courses, we have the challenge of credentialing and certifying future gynecologic
      endoscopists. The objective of this article is to propose and to illustrate a
      uniform standardized core curriculum for obstetrics and gynecology residents,
      fellows in AAGL/SRS-sponsored fellowship programs, and participants in
      postgraduate courses. Consisting of 3 discrete parts, this proposal addresses
      formal laparoscopic training for gynecologists, already implemented and available
      to general surgeons, and a novel proposition for core training in hysteroscopy.
      The curriculum is distributed in a quarterly system with specific educational
      objectives in each quarter. After quarters 1 and 2, an online examination is
      given; after quarter 3, participants are required to take and pass a hands-on
      examination at a specified testing facility; and at the end of quarter 4,
      participants must demonstrate leadership skills in the operating room and in a
      teaching capacity, and promote the principles of the AAGL.

PMID- 19406691
TI  - Effects of short-term training on heart rate dynamics in individuals with spinal
      cord injury.
AB  - Increased risk of cardiovascular diseases and autonomic dysregulation are common
      health concerns in individuals with spinal cord injury (SCI). Two therapies that
      may help improve cardiovascular control are body-weight supported treadmill
      training (BWSTT) and head-up tilt training (HUTT). The purpose of this study was
      to examine the effects of short-term BWSTT and HUTT on cardiac autonomic
      function. Seven participants (6 male, 37.1+/-7.7 years) with SCI (C5-T10, ASIA A
      C; 5.0+/-4.4 years post-injury) completed the study protocol. In this randomized
      cross-over design, participants were required to complete 4 weeks of thrice
      weekly BWSTT and HUTT (i.e. 12 sessions each), separated by a 4 week detraining
      period. Cardiac autonomic function was assessed at rest, before and after, each 4
      week training period using linear and non-linear measures (sample entropy and
      detrended fluctuation analysis (alpha(1))) of heart rate dynamics. Participants
      completed equivalent amounts of time performing BWSTT and HUTT (453.7+/-27.3 min
      vs. 471.6+/-19.7 min, p=0.24). There were no significant differences in linear
      heart rate variability following BWSTT or HUTT (p>0.05). In contrast, there was a
      significant change in sample entropy following BWSTT (1.05+/-0.14 to 1.42+/-0.12,
      p<0.05). Due to the bi-directional pattern of alpha(1) values, distance scores
      were calculated (|1-alpha(1)|) and demonstrated a significant reduction following
      BWSTT (0.54+/-0.06 to 0.26+/-0.05, p=0.001). In conclusion, 4 weeks of BWSTT but
      not HUTT training are sufficient to increase sample entropy and reduce the
      fractal scaling distance score in participants with SCI.

PMID- 19406693
TI  - Hepatic venous gas and pneumocardia.

PMID- 19406689
TI  - Decreased 4-1BB expression on HIV-specific CD4+ T cells is associated with
      sustained viral replication and reduced IL-2 production.
AB  - CD4+ T cell dysfunction in subjects with chronic HIV infection is in part due to
      an imbalance of costimulatory and coinhibitory receptors. We report that virus
      specific CD4+ T cells expressing 4-1BB (CD137) or OX40 (CD134) produced more IL-2
      than cells lacking these costimulatory receptors (P<0.05) and that 4-1BB was
      expressed at a lower level on HIV- than CMV-specific IFN-gamma and IL-2 producing
      CD4+ T cells (P<0.0001 and P<0.01, respectively). Suppression of viral
      replication with antiretroviral therapy was associated with increased 4-1BB
      expression on HIV- and CMV-specific IL-2 producing CD4+ T cells (P<0.05 and
      P<0.01, respectively) and the percentage of IL-2 producing HIV-specific CD4+ T
      cells that expressed 4-1BB was inversely correlated with HIV plasma viral load
      (r=-0.75, P=0.007). These findings indicate that the loss of 4-1BB on HIV
      specific CD4+ T cells is associated with viral replication and that it may
      contribute to reduced IL-2 production observed during chronic infection.

PMID- 19406694
TI  - Enhanced angiogenesis of porous collagen scaffolds by incorporation of TMC/DNA
      complexes encoding vascular endothelial growth factor.
AB  - Angiogenesis of an implanted construct is one of the most important issues in
      tissue engineering and regenerative medicine, and can often take as long as
      several weeks. The vascular endothelial growth factor (VEGF) shows a positive
      effect on enhancing angiogenesis in vivo. But the incorporation of growth factors
      has many limitations, since they typically have half-lives only on the order of
      minutes. Therefore, in this work the DNA encoding VEGF was applied to enhance the
      angiogenesis of a collagen scaffold. A cationic gene delivery vector, N,N,N
      trimethyl chitosan chloride (TMC), was used to form complexes with the plasmid
      DNA encoding VEGF. The complexes were then incorporated into the collagen
      scaffold, the loading being mediated by the feeding concentration and release in
      a sustained manner. In vitro cell culture demonstrated a significant improvement
      in the VEGF expression level from the TMC/DNA complexes containing scaffolds, in
      particular with a large amount of DNA. The scaffolds containing the TMC/DNA
      complexes were subcutaneously implanted into Sprague-Dawley mice to study their
      angiogenesis via macroscopic observation, hematoxylin-eosin staining and
      immunohistochemical staining. The results demonstrated that the incorporation of
      TMC/DNA complexes could effectively enhance the in vivo VEGF expression and
      thereby the angiogenesis of implanted scaffolds.

PMID- 19406695
TI  - [Evaluation of glomerular filtration rate and proteinuria for the diagnosis of
      chronic kidney disease].
AB  - An update of French position statement about estimation of glomerular filtration
      rate and proteinuria has been developed, using consensus methods. The use of a
      threshold of estimated glomerular filtration rate, uncorrected for age or sex, to
      define disease has been rightly criticised. For measurement of renal function, it
      is recommended to estimate glomerular filtration rate from serum creatinine using
      isotope dilution mass spectrometry (IDMS) traceable simplified modification of
      diet in renal disease (MDRD) equation. It is emphasized that the degree of
      proteinuria is a significant risk factor for progression of chronic kidney
      disease and for cardiovascular disease. The staging system (which comprises five
      stages, 1-5) defines chronic kidney disease on the basis of either evidence of
      kidney damage (proteinuria, haematuria, or anatomical abnormality) or an impaired
      glomerular filtration rate less than 60 ml/min/1.73 m(2), present on at least two
      occasions over three months or longer. The adoption of this staging system is
      recommended.

PMID- 19406696
TI  - [Recommendations before travelling for renal transplant patients].
AB  - Travel is now a reasonable objective of CKD patients after renal transplantation.
      However, immunosuppressive treatment makes them particularly susceptible to
      infections and may interfere with vaccinations and other drugs. Travel in
      countries with low health level should be strongly discouraged in the first six
      months after transplantation or following an acute event. Otherwise, specific
      consultations should be arranged to prepare the patient as soon as possible.
      Vaccinations should be started early before departure. Specific immunisations
      include vaccines against hepatitis A, typhoid, meningococcus and rabies in some
      cases. Living vaccines are formally contra-indicated. Particular attention should
      be paid for protection against insects because this is the only effective measure
      against diseases. In the case of malaria, it should be complemented by adapted
      chemoprophylaxis that should be started 15 days before the departure date. Advice
      on hygiene measures should be clarified because this can prevent numerous
      infections, especially of the digestive tract. Advice on the management of
      diarrhoea is essential, especially in terms of preventing dehydration. Finally,
      advice about transport and physical risks, especially those related to sun
      exposure, should also be addressed.

PMID- 19406697
TI  - Influence of Pb and La contents on the lattice configuration of La-substituted
      Pb(Zr,Ti)O3 films fabricated by CSD method.
AB  - The influence of Pb and La contents on the lattice configuration in La
      substituted Pb(Zr0(.65),Ti0(.35))O3 (La- PZT) films was systematically
      investigated. La-PZT films with various La and Pb contents were fabricated on
      Pt/Ti/SiO(2)/Si substrates by chemical solution deposition (CSD). In the La- PZT
      films with a Pb content ratio of 125% relative to a stoichiometric value, La ions
      were substituted for not only A-site ions but also B-site ions at La contents
      greater than 3 mol%. La substitution for B-site seems to cause larger reduction
      of the unit cell size. In addition, we found that in the La-PZT films with a La
      content of 3 mol%, the Pb content of 116 mol% (120% relative to a stoichiometric
      value) was optimum from the viewpoint of site occupancy. This indicates that
      excess Pb prevented the A-site substitution of La ions.

PMID- 19406698
TI  - Nonlinear pyroelectric energy harvesting from relaxor single crystals.
AB  - Energy harvesting from temperature variations in a
      Pb(Zn(1/3)Nb(2/3))(0.955)Ti(0.045)O(3) single crystal was studied and evaluated
      using the Ericsson thermodynamic cycle. The efficiency of this cycle related to
      Carnot cycle is 100 times higher than direct pyroelectric energy harvesting, and
      it can be as high as 5.5% for a 10 degrees C temperature variation and 2 kV/mm
      electric field. The amount of harvested energy for a 60 degrees C temperature
      variation and 2 kV/mm electric field is 242.7 mJ x cm(-3). The influence of
      ferroelectric phase transitions on the energy harvesting performance is discussed
      and illustrated with experimental results.

PMID- 19406699
TI  - Adaptive spectral doppler estimation.
AB  - In this paper, 2 adaptive spectral estimation techniques are analyzed for
      spectral Doppler ultrasound. The purpose is to minimize the observation window
      needed to estimate the spectrogram to provide a better temporal resolution and
      gain more flexibility when designing the data acquisition sequence. The methods
      can also provide better quality of the estimated power spectral density (PSD) of
      the blood signal. Adaptive spectral estimation techniques are known to provide
      good spectral resolution and contrast even when the observation window is very
      short. The 2 adaptive techniques are tested and compared with the averaged
      periodogram (Welch's method). The blood power spectral capon (BPC) method is
      based on a standard minimum variance technique adapted to account for both
      averaging over slow-time and depth. The blood amplitude and phase estimation
      technique (BAPES) is based on finding a set of matched filters (one for each
      velocity component of interest) and filtering the blood process over slow-time
      and averaging over depth to find the PSD. The methods are tested using various
      experiments and simulations. First, controlled flow-rig experiments with steady
      laminar flow are carried out. Simulations in Field II for pulsating flow
      resembling the femoral artery are also analyzed. The simulations are followed by
      in vivo measurement on the common carotid artery. In all simulations and
      experiments it was concluded that the adaptive methods display superior
      performance for short observation windows compared with the averaged periodogram.
      Computational costs and implementation details are also discussed.

PMID- 19406700
TI  - Fractional derivative models for ultrasonic characterization of polymer and
      breast tissue viscoelasticity.
AB  - The viscoelastic response of hydropolymers, which include glandular breast
      tissues, may be accurately characterized for some applications with as few as 3
      rheological parameters by applying the Kelvin-Voigt fractional derivative (KVFD)
      modeling approach. We describe a technique for ultrasonic imaging of KVFD
      parameters in media undergoing unconfined, quasi-static, uniaxial compression. We
      analyze the KVFD parameter values in simulated and experimental echo data
      acquired from phantoms and show that the KVFD parameters may concisely
      characterize the viscoelastic properties of hydropolymers. We then interpret the
      KVFD parameter values for normal and cancerous breast tissues and hypothesize
      that this modeling approach may ultimately be applied to tumor differentiation.

PMID- 19406701
TI  - Basic considerations in the use of coded excitation for color flow imaging
      applications.
AB  - Coded excitation is now a well-established technique in medical ultrasound for B
      mode imaging applications. It enables a gain in depth of penetration, without
      sacrificing the spatial resolution and maintaining an acceptable peak intensity
      for patient safety. The rationale of this technique for velocity estimation
      applications still has to be formulated in more precise terms. In particular,
      differences in the situation that arise in color flow imaging (CFI) applications
      from typical B-mode imaging conditions, such as signal-to-noise ratio conditions,
      pulsing strategy, and safety requirements, need to be specifically addressed to
      assess more quantitatively the potential of this technique. This paper discusses
      the potential improvement in sensitivity, resolution, and statistical performance
      provided by coded excitation for CFI applications from theoretical considerations
      and simulations.

PMID- 19406702
TI  - Numerical analysis of variability in ultrasound propagation properties induced by
      trabecular microstructure in cancellous bone.
AB  - The manner by which the trabecular microstructure affects the propagation of
      ultrasound waves through cancellous bone is numerically investigated by finite
      difference time-domain (FDTD) simulation. Sixteen 3-D numerical models of 6.45 x
      6.45 x 6.45 mm with a voxel size of 64.5 microm are reconstructed using a 3-D
      microcomputed tomographic (microCT) image taken from a bovine cancellous bone
      specimen of approximately 20 x 20 x 9 mm. All cancellous bone models have an
      oriented trabecular structure, and their trabecular elements are gradually eroded
      to increase the porosity using an image processing technique. Three erosion
      procedures are presented to realize various changes in the trabecular
      microstructure with increasing porosity. FDTD simulations of the ultrasound pulse
      waves propagating through the cancellous bone models at each eroded step are
      performed in 2 cases of the propagations parallel and perpendicular to the major
      trabecular orientation. The propagation properties of the wave amplitudes and
      propagation speeds are derived as a function of the porosity, and their
      variability due to the trabecular microstructure is revealed. To elucidate an
      effect of the microstructure, the mean intercept length (MIL), which is a
      microstructural parameter, is introduced, and the correlations of the propagation
      properties with the MILs of the trabecular elements and pore spaces are
      investigated.

PMID- 19406704
TI  - The application of synthetic focusing for imaging crack-like defects in pipelines
      using guided waves.
AB  - This paper deals with quantifying the performance of a technique for detection,
      location, and sizing of circumferential crack-like defects in pipelines using
      synthetically focused guided waves. The system employs a circumferential array of
      piezoelectric transducer elements. A torsional probing guided wave is excited
      using the array, which subsequently interacts with the reflecting features of the
      pipe, such as defects or weld caps. The recorded backscattered signals are
      synthetically focused to every point of interest in the pipe wall, to form an
      image of the reflecting features of the pipe. The defect image amplitude is used
      to estimate the defect depth, and the full width at half maximum of the defect
      image circumferential profile is used to estimate the circumferential extent of
      the defect. The imaging system is tested with data from finite element
      simulations and from laboratory experiments. It is found that reliable sizing of
      circumferential cracks in finite element simulations and experiments can be
      achieved if the circumferential extent of the defect is greater than 1.5
      lambda(S), where lambda(S) is the shear wavelength at the frequency of
      inspection. This result is theoretically valid for any pipe size, any axial
      defect location, and any inspection frequency. Amplitude gains of around 18 dB
      over an unfocused system have been observed experimentally in an 8-inch pipe with
      a 9 dB SNR improvement.

PMID- 19406703
TI  - Error in estimates of tissue material properties from shear wave dispersion
      ultrasound vibrometry.
AB  - Shear wave velocity measurements are used in elasticity imaging to find the shear
      elasticity and viscosity of tissue. A technique called shear wave dispersion
      ultrasound vibrometry (SDUV) has been introduced to use the dispersive nature of
      shear wave velocity to locally estimate the material properties of tissue. Shear
      waves are created using a multifrequency ultrasound radiation force, and the
      propagating shear waves are measured a few millimeters away from the excitation
      point. The shear wave velocity is measured using a repetitive pulse-echo method
      and Kalman filtering to find the phase of the harmonic shear wave at 2 different
      locations. A viscoelastic Voigt model and the shear wave velocity measurements at
      different frequencies are used to find the shear elasticity (mu(1)) and viscosity
      (mu(2)) of the tissue. The purpose of this paper is to report the accuracy of the
      SDUV method over a range of different values of mu(1) and mu(2). A motion
      detection model of a vibrating scattering medium was used to analyze measurement
      errors of vibration phase in a scattering medium. To assess the accuracy of the
      SDUV method, we modeled the effects of phase errors on estimates of shear wave
      velocity and material properties while varying parameters such as shear stiffness
      and viscosity, shear wave amplitude, the distance between shear wave measurements
      (delta r), signal-to-noise ratio (SNR) of the ultrasound pulse-echo method, and
      the frequency range of the measurements. We performed an experiment in a section
      of porcine muscle to evaluate variation of the aforementioned parameters on the
      estimated shear wave velocity and material property measurements and to validate
      the error prediction model. The model showed that errors in the shear wave
      velocity and material property estimates were minimized by maximizing shear wave
      amplitude, pulse-echo SNR, delta r, and the bandwidth used for shear wave
      measurements. The experimental model showed optimum performance could be obtained
      for delta r = 3 - 6 mm, SNR =35 dB, with a frequency range of 100 to 600 Hz, and
      with a shear wave amplitude on the order of a few microns down to 0.5 microm. The
      model provides a basis to explore different parameters related to implementation
      of the SDUV method. The experiment confirmed conclusions made by the model, and
      the results can be used for optimization of SDUV.

PMID- 19406705
TI  - High-frequency tortuosity relaxation in open-cell foams.
AB  - Propagation of ultrasounds through open-cell polymeric foams is studied using air
      coupled ultrasound and Fourier spectral analysis (both phase and magnitude) in
      the frequency range 0.1 to 6 MHz. A detailed micrographic study is first
      performed to determine struts dimensions and cell geometry, hence, a unit cell
      model to describe these foams is proposed. Ultrasound phase velocity and
      transmission loss were then measured. Variation of these magnitudes with the
      frequency follows the shape of a sigmoid growth. This behavior of the phase
      velocity can be explained by introducing an apparent tortuosity with a relaxation
      like behavior, which can be explained by considering a probabilistic tortuous
      walk, as it has recently been performed for other kind of foams. However and
      unlike in previous studies, the present one shows the whole transition of this
      sigmoid growth for all studied foams. This is achieved by a precise selection of
      the foam samples and by the fabrication of new air-coupled transducers that
      enlarge the experimental working frequency range to lower frequencies. The study
      of the measured sigmoid growth is used to determine the probability function,
      required by the probabilistic tortuous walk model, which best describes the
      variation of the apparent tortuosity.

PMID- 19406706
TI  - A lateral-field-excited LiTaO3 high-frequency bulk acoustic wave sensor.
AB  - The most popular bulk acoustic wave (BAW) sensor is the quartz crystal
      microbalance (QCM), which has electrodes on both the top and bottom surfaces of
      an AT-cut quartz wafer. In the QCM, the exciting electric field is primarily
      perpendicular to the crystal surface, resulting in a thickness field excitation
      (TFE) of a resonant temperature compensated transverse shear mode (TSM). The TSM,
      however, can also be excited by lateral field excitation (LFE) in which
      electrodes are placed on one side of the wafer leaving a bare sensing surface
      exposed directly to a liquid or a chemi/bio selective layer allowing the
      detection of both mechanical and electrical property changes caused by a target
      analyte. The use of LFE sensors has motivated an investigation to identify other
      piezoelectric crystal orientations that can support temperature-compensated TSMs
      and operate efficiently at high frequencies resulting in increased sensitivity.
      In this work, theoretical search and experimental measurements are performed to
      identify the existence of high-frequency temperature-compensated TSMs in
      LiTaO(3). Prototype LFE LiTaO(3) sensors were fabricated and found to operate at
      frequencies in excess of 1 GHz and sensitively detect viscosity, conductivity,
      and dielectric constant changes in liquids.

PMID- 19406707
TI  - Pulse echo and combined resonance techniques: a full set of LGT acoustic wave
      constants and temperature coefficients.
AB  - This work reports on the determination of langatate elastic and piezoelectric
      constants and their associated temperature coefficients employing 2 independent
      methods, the pulse echo overlap (PEO) and a combined resonance technique (CRT) to
      measure bulk acoustic wave (BAW) phase velocities. Details on the measurement
      techniques are provided and discussed, including the analysis of the couplant
      material in the PEO technique used to couple signal to the sample, which showed
      to be an order of magnitude more relevant than the experimental errors involved
      in the data extraction. At room temperature, elastic and piezoelectric constants
      were extracted by the PEO and the CRT methods and showed results consistent to
      within a few percent for the elastic constants. Both raw acquired data and
      optimized constants, based on minimization routines applied to all the modes
      involved in the measurements, are provided and discussed. Comparison between the
      elastic constants and their temperature behavior with the literature reveals the
      recent efforts toward the consistent growth and characterization of LGT, in spite
      of significant variations (between 1 and 30%) among the constants extracted by
      different groups at room temperature. The density, dielectric permittivity
      constants, and respective temperature coefficients used in this work have also
      been independently determined based on samples from the same crystal boule. The
      temperature behavior of the BAW modes was extracted using the CRT technique,
      which has the advantage of not relying on temperature dependent acoustic
      couplants. Finally, the extracted temperature coefficients for the elastic and
      piezoelectric constants between room temperature and 120 degrees C are reported
      and discussed in this work.

PMID- 19406708
TI  - Ultrasonic trapping of small particles by a vibrating rod.
AB  - In this paper, the ultrasonic trapping of small particles by a vibrating rod is
      proposed and analyzed. An aluminum rod, which is driven by an actuator and
      operates in the 0 th order vibration mode (back and forth vibration mode), can
      trap small particles in water. The experimental phenomena and the trapping
      mechanism are theoretically analyzed, and the acoustic radiation force acting on
      a spherical particle near the surface of the vibrating rod is estimated. The
      effects of operating frequency, rod radius, particle radius and other physical
      parameters are investigated experimentally and theoretically, and useful
      guidelines to optimize the trapping capability are proposed.

PMID- 19406709
TI  - Full-wave analysis of piezoelectric boundary waves propagating along metallic
      grating sandwiched between two semi-infinite layers.
AB  - This paper describes full-wave analysis of piezoelectric boundary acoustic waves
      (PBAWs) propagating along a metallic grating sandwiched between 2 semi-infinite
      layers. In the analysis, the finite element method (FEM) is used for the grating
      region while the spectral domain analysis (SDA) is applied for an isotropic
      overlay region as well as a piezoelectric substrate region. The combination of
      the FEM and SDA makes the numerical analysis very fast and precise. As an
      example, the analysis was made on the PBAWs propagating in an SiO2 overlay/Cu
      grating/rotated Y-cut LiNbO(3) structure. It is shown that both the shear
      horizontal (SH) type and Rayleigh-type PBAWs are supported in the structure, and
      that their velocities are very close to each other. Thus spurious responses due
      to the Rayleigh-type PBAW should completely be suppressed for device
      implementation. Discussions are made in detail on the influence of Cu grating
      thickness, substrate rotation angle, and metallization ratio on excitation and
      propagation characteristics of the SH- and Rayleigh-type PBAWs.

PMID- 19406710
TI  - Feasibility of ultra-wideband SAW RFID tags meeting FCC rules.
AB  - We discuss the feasibility of surface acoustic wave (SAW) radio-frequency
      identification (RFID) tags that rely on ultra-wideband (UWB) technology. We
      propose a design of a UWB SAW tag, carry out numerical experiments on the device
      performance, and study signal processing in the system. We also present
      experimental results for the proposed device and estimate the potentially
      achievable reading distance. UWB SAW tags will have an extremely small chip size
      (<0.5 x 1 mm(2)) and a low cost. They also can provide a large number of
      different codes. The estimated read range for UWB SAW tags is about 2 m with a
      reader radiating as low as <0.1 mW power levels with an extremely low duty
      factor.

PMID- 19406711
TI  - The use of real or complex coupling coefficients for lossy piezoelectric
      materials.
AB  - Two competing approaches for calculating coupling coefficients for lossy
      piezoelectric materials, one producing a real result and the other a complex
      result, are compared and analyzed. It is found that the complex coupling
      coefficient suffers from mathematical difficulties, which the real coupling
      coefficient does not exhibit. Moreover, it is pointed out that a prediction made
      by the complex coupling coefficient theory conflicts with experiment while the
      corresponding real coupling coefficient theory prediction does not. When a
      coupling coefficient of interest has been computed from the real coupling
      coefficient theory using piezoelectric equations having intensive independent
      variables, the resulting expression has the same algebraic form as the
      corresponding static coupling coefficient formula. Moreover, only the real parts
      of the piezoelectric, elastic, and dielectric material properties appear.

PMID- 19406712
TI  - Fabrication and performance of high-frequency composite transducers with
      triangular-pillar geometry.
AB  - A single-element, 40-MHz, 3-mm diameter transducer was fabricated with a
      geometric focus at 9 mm. The transducer was based on a piezo-composite substrate
      with triangular-shaped composite pillars. The 2-way bandwidth of 50% and
      impedance magnitude were in agreement with that predicted using finite-element
      modeling. A one-way radiation pattern was collected using a needle hydrophone.
      The one-way -3 dB beamwidth at the geometric focus was measured to be 120 microm
      and the -3 dB depth of field was 2.5 mm. This is in good agreement with the
      theoretical predictions of 112.5 microm and 2.4 mm. The triangular-pillar
      composite transducer was then compared with a transducer with square composite
      pillars with similar volume fraction of active ceramic. A 9.5 dB reduction in the
      amplitude of the secondary resonance was found for the triangular-pillar
      composite as well as a 30% gain in the 2-way pulse bandwidth. A 256-element 30
      MHz linear array was fabricated as a preliminary investigation into the use of
      the triangular pillar as the substrate in a high-frequency linear array
      transducer. In vivo images were generated with both the single-element and linear
      array transducers.

PMID- 19406713
TI  - A 256 x 256 2-D array transducer with row-column addressing for 3-D rectilinear
      imaging.
AB  - We present simulation and experimental results from a 5-MHz, 256 x 256 2-D
      (65,536 elements, 38.4 x 38.4 mm) 2-D array transducer with row-column
      addressing. The main benefits of this design are a reduced number of
      interconnects, a modified transmit/receive switching scheme with a simple diode
      circuit, and an ability to perform volumetric imaging of targets near the
      transducer with transmit beamforming in azimuth and receive beamforming in
      elevation. The final dimensions of the transducer were 38.4 mm x 38.4 mm x 300
      microm. After a row-column transducer was prototyped, the series resonance
      impedance was 104 Omega at 5.4 MHz. The measured -6 dB fractional bandwidth was
      53% with a center frequency of 5.3 MHz. The SNR at the transmit focus was
      measured to be 30 dB. At 5 MHz, the average nearest neighbor crosstalk was -25
      dB. In this paper, we present 3-D images of both 5 pairs of nylon wires embedded
      in a clear gelatin phantom and an 8 mm diameter cylindrical anechoic cyst phantom
      acquired from a 256 x 256 2-D array transducer made from a 1-3 composite. We
      display the azimuth and elevation B-scans as well as the C-scan for each image.
      The cross-section of the wires is visible in the azimuth B-scan, and the long
      axes can be seen in the elevation B-scan and C-scans. The pair of wires with 1-mm
      axial separation is discernible in the elevational B-scan. When a single wire
      from the wire target phantom was used, the measured lateral beamwidth was 0.68 mm
      and 0.70 mm at 30 mm depth in transmit beamforming and receive beamforming,
      respectively, compared with the simulated beamwidth of 0.55 mm. The cross-section
      of the cyst is visible in the azimuth B-scan whereas the long axes can be seen as
      a rectangle in the elevation B-scan and C-scans.

PMID- 19406714
TI  - Airborne ultrasonic phased arrays using ferroelectrets: a new fabrication
      approach.
AB  - In this work, a novel procedure that considerably simplifies the fabrication
      process of ferroelectret-based multielement array transducers is proposed and
      evaluated. Also, the potential of ferroelectrets being used as active material
      for air-coupled ultrasonic transducer design is demonstrated. The new
      construction method of multi-element transducers introduces 2 distinctive
      improvements. First, active ferroelectret material is not discretized into
      elements, and second, the need of structuring upper and/or lower electrodes in
      advance of the permanent polarization of the film is removed. The aperture
      discretization and the mechanical connection are achieved in one step using a
      through-thickness conductive tape. To validate the procedure, 2 linear array
      prototypes of 32 elements, with a pitch of 3.43 mm and a wide usable frequency
      range from 30 to 300 kHz, were built and evaluated using a commercial phased
      array system. A low crosstalk among elements, below -30 dB, was measured by
      interferometry. Likewise, a homogeneous response of the array elements, with a
      maximum deviation of +/-1.8 dB, was obtained. Acoustic beam steering measurements
      were accomplished at different deflection angles using a calibrated microphone.
      The ultrasonic beam parameters, namely, lateral resolution, side lobe level,
      grating lobes, and focus depth, were congruent with theory. Acoustic images of a
      single reflector were obtained using one of the array elements as the receiver.
      Resulting images are also in accordance with numerical simulation, demonstrating
      the feasibility of using these arrays in pulse-echo mode. The proposed procedure
      simplifies the manufacturing of multidimensional arrays with arbitrary shape
      elements and not uniformly distributed. Furthermore, this concept can be extended
      to nonflat arrays as long as the transducer substrate conforms to a developable
      surface.

PMID- 19406715
TI  - Reduced harmonic representation for continuous wave, shock-producing focused
      beams.
AB  - An extension to the frequency domain solution to Burgers' equation (FDSBE) is
      presented in the context of a continuous wave, nonlinear beam propagation model.
      The extension adds a specified number of harmonics to each FDSBE nonlinear
      substep in the shock-bearing region. The extension harmonics have amplitudes
      given by a 1/n amplitude decay assumption. The corresponding phases are given by
      linear extrapolation. The extension scheme allows for stable and accurate,
      reduced harmonic focal beam modeling. An algorithm is also presented that allows
      this scheme to provide accurate heating rate and radiation force output.

PMID- 19406716
TI  - Filled and unfilled temperature-dependent epoxy resin blends for lossy transducer
      substrates.
AB  - In the context of our ongoing investigation of low-cost 2-dimensional (2-D)
      arrays, we studied the temperature- dependent acoustic properties of epoxy blends
      that could serve as an acoustically lossy backing material in compact 2-D array
      based devices. This material should be capable of being machined during array
      manufacture, while also providing adequate signal attenuation to mitigate backing
      block reverberation artifacts. The acoustic impedance and attenuation of 5
      unfilled epoxy blends and 2 filled epoxy blends - tungsten and fiberglass fillers
      - were analyzed across a 35 degrees C temperature range in 5 degrees C
      increments. Unfilled epoxy materials possessed an approximately linear variation
      of impedance and sigmoidal variation of attenuation properties over the range of
      temperatures of interest. An intermediate epoxy blend was fitted to a quadratic
      trend line with R(2) values of 0.94 and 0.99 for attenuation and impedance,
      respectively. It was observed that a fiberglass filler induces a strong quadratic
      trend in the impedance data with temperature, which results in increased error in
      the characterization of attenuation and impedance. The tungsten-filled epoxy was
      not susceptible to such problems because a different method of fabrication was
      required. At body temperature, the tungsten-filled epoxy could provide a 44 dB
      attenuation of the round-trip backing block echo in our application, in which the
      center frequency is 5 MHz and the backing material is 1.1 mm thick. This is an 11
      dB increase in attenuation compared with the fiberglass-filled epoxy in the
      context of our application. This work provides motivation for exploring the use
      of custom-made tungsten-filled epoxy materials as a substitute PCB-based
      substrate to provide electrical signal interconnect.

PMID- 19406717
TI  - Low acoustic attenuation silicone rubber lens for medical ultrasonic array probe.
AB  - Effects of heavy density (rho = 9.2 x 10(3) kg/m(3)) Yb(2)O(3) fine dopant (16 nm
      in diameter) on the acoustic properties of a high-temperature-vulcanization (HTV)
      silicone rubber have been investigated, to develop a new acoustic lens material
      with a low acoustic attenuation (alpha) for the medical array probe application.
      The HTV silicone rubber has advantages in that it shows a lower alpha than that
      of a room-temperature-vulcanization (RTV) silicone rubber and it can be mixed by
      applying shear stress, using roll-milling equipment. Roll-milling time dependence
      of the HTV silicone rubber indicates that the alpha is closely affected by the
      dispersion of nanopowders in the rubber matrix. The 8 vol% Yb(2)O(3)-doped HTV
      silicone rubber mixed for 30 min showed the lowest alpha of 0.73 dB/mm MHz with
      an acoustic impedance [AI = sound speed (c) x density (rho)] of 1.43 x 10(6)
      kg/m(2)s at 37 degrees C. Moreover, simulation results reveal that a 5 MHz linear
      probe using the HTV silicone rubber doped with Yb(2)O(3) powder showed relative
      sensitivity around 2.6 to 3.0 dB higher than a probe using RTV silicone rubber
      doped with Yb(2)O(3) powder or SiO2-doped conventional silicone rubber for the
      ultrasonic medical application.

PMID- 19406718
TI  - Thickness-shear vibration of an AT-cut quartz plate with elliptical electrodes
      and implications in optimal blank geometry.
AB  - We analyze thickness-shear vibration of an AT-cut quartz plate with elliptical
      electrodes. The electrodes are essentially optimal in the sense of Mindlin in
      that they approximately satisfy the criterion for Bechmann's number in every
      direction. The results of our analysis suggest that optimal crystal blank
      geometry is essentially elliptical. We also suggest a way of machining elliptical
      crystal blanks.

PMID- 19406719
TI  - Three-dimensional reconstruction of the "bright ring" echogenicity from porcine
      blood upstream in a stenosed tube.
AB  - To investigate the echogenicity variation due to blood flow disturbance near a
      stenosis under pulsatile flow, a series of in vitro experiments were performed in
      a rigid tube with an eccentric stenosis of 70% area reduction in a mock flow
      loop. An ultrasonic B-mode with a Doppler spectrogram was used to correlate
      echogenicity with flow speed and stroke rate. This paper reports echogenicity
      variation upstream of a stenosis under pulsatile flow. The experimental results
      showed that blood flow disturbed by the stenosis affects echogenicity and red
      blood cell rouleaux upstream. A hypoechoic "black hole" was shown at the center
      of the stream at systole. During diastole, the "bright ring" in cross-sectional
      images was observed as eddy-like or parabolic profiles in longitudinal images.
      These images could be reconstructed into a 3-dimensional animation, providing a
      better understanding of dynamic changes of the rouleaux distribution upstream of
      a stenosis under pulsatile flow.

PMID- 19406721
TI  - The role of biomarkers in the management of patients with lymphoma: promise
      versus reality.

PMID- 19406722
TI  - Meeting Highlights from: The 50th annual meeting of the American Society of
      Hematology; San Francisco, CA; December 6-9, 2008.

PMID- 19406723
TI  - CD43 expression is an adverse prognostic factor in diffuse large B-Cell lymphoma.
AB  - BACKGROUND: CD43 is a transmembrane glycoprotein expressed in different
      hematopoietic cells, including some subsets of B lymphocytes. About a quarter of
      diffuse large B-cell lymphomas (DLBCLs) express CD43, but its prognostic
      significance is unknown. PATIENTS AND METHODS: We analyzed the prognostic effect
      of immunohistochemically determined CD43 expression in 119 patients with newly
      diagnosed DLBCL. All were treated with CHOP
      (cyclophosphamide/doxorubicin/vincristine/prednisone)-like chemotherapy, 57
      without and 62 with rituximab. RESULTS: A total of 31 DLBCL cases (26%) expressed
      CD43. Patients with CD43+ and CD43- lymphomas did not differ regarding sex,
      International Prognostic Index (IPI) factors and score, rituximab treatment,
      presence of bulky disease, or germinal center subtype. Median follow-up was 45
      months. Patients with CD43+ DLBCL had significantly lower complete response rates
      (59% vs. 80%; P = .019), 2-year event-free survival (EFS) rates (34% vs. 64%; P =
      .003), and overall survival (OS) rates (45% vs. 76%; P = .002). The prognostic
      significance of CD43 expression was retained in multivariate analysis (relative
      risk [RR] 2.04; P = .013 for EFS; RR 2.17; P = .016 for OS). In subgroup
      analysis, the effect of CD43 expression was significant in patients treated with
      rituximab and those with low IPI, whereas it was not reached in patients treated
      without rituximab. The effect was not observed in patients with high IPI.
      CONCLUSION: These results indicate that CD43 expression is an important
      independent adverse prognostic factor in DLBCL.

PMID- 19406724
TI  - Response-guided ABVD chemotherapy plus involved-field radiation therapy for
      intermediate-stage Hodgkin lymphoma in the pre-positron emission tomography era:
      a Gruppo Italiano Studio Linfomi (GISL) prospective trial.
AB  - PURPOSE: In the pre-positron emission tomography era, the Gruppo Italiano Studio
      Linfomi (GISL) investigated the feasibility and efficacy of a treatment based on
      a response-tailored number of doxorubicin/bleomycin/vinblastine/dacarbazine
      (ABVD) courses in 218 intermediate-stage Hodgkin lymphoma patients. PATIENTS AND
      METHODS: Patients with stage I/II showing at least one adverse prognostic factor
      and stage IIIA without adverse prognostic factors were recruited. Treatment
      included a first step of 3 ABVD courses, followed by an early-restaging. Patients
      in CR/CRu received 1 additional ABVD cycle, patients in PR received 3 more ABVD,
      and nonresponder patients went off study. Involved-field radiation therapy (RT)
      was recommended on chemotherapy completion. RESULTS: The median age was 30 years
      (range, 15-68 years) and 131 patients (61%) were female. Seven percent of
      patients were in stage I, 78% in stage II, and 15% in stage III; B-symptoms,
      bulky tumor and erythrocyte sedimentation rate > 30 were recorded in 20%, 26%,
      and 43% of cases, respectively. The CR/CRu rate was 62% at early restaging, 72%
      at the end of chemotherapy, and 95% following RT. With a median follow-up of 74
      months (range, 6-193 months), 7-year overall survival, relapse-free survival, and
      freedom from treatment failure were 91.8% (95% CI, 86%-95.5%), 89.2% (95% CI,
      82.8%-93.3%), and 81.8% (95% CI, 75.2%-86.7%), respectively. Patients in CR/CRu
      on early restaging, receiving 4 ABVD, had an excellent outcome with 7-year RFS
      and cause-specific survival similar to those of the late responders treated with
      6 ABVD (RFS, 87.5% vs. 90.5% and CSS, 96.6% vs. 92.7%, respectively). CONCLUSION:
      The response-guided ABVD program we report, based on standard clinical staging
      procedures, proved to be feasible and safe in patients with intermediate-stage
      Hodgkin lymphoma.

PMID- 19406725
TI  - Melphalan, prednisone, and lenalidomide for newly diagnosed myeloma: kinetics of
      neutropenia and thrombocytopenia and time-to-event results.
AB  - BACKGROUND: Initial analysis of the combination melphalan, prednisone, plus
      lenalidomide (MPR) showed significant antimyeloma activity in patients with
      untreated multiple myeloma, with neutropenia and thrombocytopenia as the most
      frequent side effects. This updated analysis reassessed the kinetics of
      neutropenia and thrombocytopenia as well as the safety and efficacy of MPR.
      PATIENTS AND METHODS: A total of 21 patients with newly diagnosed myeloma
      received melphalan 0.18 mg/kg on days 1-4, prednisone 2 mg/kg on days 1-4, and
      lenalidomide 10 mg daily on days 1-21 for nine 28-day cycles, followed by
      maintenance therapy with lenalidomide 10 mg daily on days 1-21. RESULTS: Grade
      3/4 neutropenia occurred in 52% of the patients, and granulocyte
      colonystimulating factor was administered in 43%. The mean neutrophil counts at
      the start of each MPR cycle, during nadir, and after 6 months of maintenance were
      2.69 x 109/L, 1.43 x 109/L, and 2.11 x 109/L, respectively. Grade 3/4
      thrombocytopenia occurred in 24% of the patients. Platelet transfusions were
      required by 1 patient (5%) with a platelet count of 16 x 109/L; however, no
      thrombocytopenia-associated bleeding was reported. The mean platelet counts at
      the start of each cycle, during nadir, and after 6 months of maintenance were 174
      x 109/L, 121 x 109/L, and 158 x 109/L, respectively. Median follow-up was 29.6
      months, median progression-free survival was 28.5 months, and 2-year overall
      survival was 91%. CONCLUSION: MPR is a promising regimen with manageable
      hematologic toxicity.

PMID- 19406726
TI  - Varicella-zoster virus prophylaxis with low-dose acyclovir in patients with
      multiple myeloma treated with bortezomib.
AB  - BACKGROUND: Varicella-zoster virus (VZV) reactivation is a common complication in
      patients with multiple myeloma (MM) treated with bortezomib, with an incidence
      rate of 10%-60%. The aim of our study was to analyze the effect of acyclovir
      prophylaxis in this patient population. PATIENTS AND METHODS: We studied 98
      consecutive patients with relapsed MM treated with bortezomib. Bortezomib 1.3
      mg/m2 was given on days 1, 4, 8, and 11 of a 21-day cycle. At first, patients did
      not receive any VZV prophylaxis, but because of the high incidence of VZV
      reactivation, VZV prophylaxis with acyclovir was implemented subsequently.
      RESULTS: A total of 11 patients treated with bortezomib did not have any VZV
      prophylaxis, and 4 of these 11 patients (36%) developed VZV reactivation in the
      form of herpes zoster. No VZV reactivations were observed in the 32 patients who
      received acyclovir 400 mg 3 times daily or the 55 patients who received acyclovir
      in a dose reduced to 400 mg once daily during bortezomib treatment. CONCLUSION:
      Varicellazoster virus reactivation is a common and serious adverse effect of
      bortezomib treatment. Acyclovir 400 mg once daily is sufficient to protect from
      VZV reactivation in patients with MM treated with bortezomib.

PMID- 19406727
TI  - A pharmacokinetic study evaluating the relationship between treatment efficacy
      and incidence of adverse events with thalidomide plasma concentrations in
      patients with refractory multiple myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) is a clonal disorder of plasma cells,
      accounting for 10% of hematologic malignancies. Relapsed or refractory MM has a
      poor prsognosis. Thalidomide has been reported to be effective for these
      patients; however, high-dose thalidomide has induced many adverse events,
      including in the nervous, gastrointestinal, and hematopoietic systems in
      approximately 20%-50% of patients. Recently, low-dose thalidomide therapy has
      been used in many countries in order to reduce these adverse events. The
      objective of this study was to determine whether plasma concentration of
      thalidomide is related to the efficacy and the development of adverse events in
      patients with refractory MM treated with low-dose thalidomide plus low-dose
      dexamethasone. PATIENTS AND METHODS: A total of 66 patients (age range, 40-74
      years) presenting with progressive disease after previous treatments were treated
      with low-dose thalidomide and low-dose dexamethasone. Thalidomide was
      administered orally at 100 mg/day for the first week. When severe adverse events
      did not develop, the dose was increased to 200 mg/day in the second week and was
      continued until progression. Dexamethasone was administered at a dose of 4 mg/day
      for the first 4 weeks, then decreased by 1 mg every week, and finally maintained
      at 1 mg/day. Plasma trough concentration of thalidomide 3 days after thalidomide
      treatment was analyzed by high-performance liquid chromatography in 45 patients
      (age range, 42-74 years) who agreed to participate in this study of thalidomide
      concentration analysis. RESULTS: The mean concentrations at 100 mg/day and 200
      mg/day were 0.343 microg/mL (range, 0.05-1.45 microg/mL) and 0.875 microg/mL
      (range, 0.19-2.09 microg/mL), respectively. The overall response rate (near
      complete response + partial response + minimal response) of this treatment was
      73%. Five had stable disease, and 3 patients experienced progressive disease.
      There was no relationship between the concentration of thalidomide in the plasma
      and the efficacy (P > .8). Severe adverse events, including grade > 2
      nonhematologic and grade > 3 hematologic adverse events, were observed in 21
      patients (46.6%). There was no significant difference in the concentration of
      thalidomide between the patients with and without severe adverse events (P >
      .843). CONCLUSION: The thalidomide concentration in the plasma does not predict
      treatment efficacy and the development of adverse events.

PMID- 19406728
TI  - Biomarkers and prognosis in malignant lymphomas.
AB  - Approximately 100 hematologists and pathologists from Europe, the United States,
      and Canada participated in the workshop Biomarkers and Prognosis in Malignant
      Lymphomas, held in Mandelieu, France, April 11-13, 2008, under the leadership of
      Anton Hagenbeek, Randy Gascoyne, and Gilles Salles. International experts in the
      field (discussed herein) shared their experiences in exploring the role of a
      variety of biologic markers related to different types of non-Hodgkin lymphomas
      (follicular, diffuse large B-cell, mantle cell, and Burkitt lymphomas) as well as
      Hodgkin lymphoma. The final goal of this clinical research is to develop new
      biologic prognostic indices for these major subtypes of lymphoma. In recent
      years, various prognostic indices, mainly based on clinical characteristics of
      the patient at diagnosis, have served to determine the prognostic profile and to
      develop prognostic factor-based treatment strategies. However, it is now time to
      reconsider this based on the wealth of new biologic information directly related
      to lymphoma cells and the surrounding cells. In this workshop, organized by the
      European School of Hematology and the European Hematology Association, the latest
      developments on molecular pathogenesis, new biomarkers, and their relation to
      prognosis were extensively discussed. Herein, the major conclusions presented in
      the different sessions are summarized.

PMID- 19406729
TI  - Successful use of full-dose dexamethasone, high-dose cytarabine, and cisplatin as
      part of initial therapy in non-hodgkin and hodgkin lymphoma with severe hepatic
      dysfunction.
AB  - Anthracycline-based chemotherapy is the cornerstone of modern curative regimens
      for aggressive lymphomas; however, these drugs cannot be safely administered in
      the setting of severe hepatic dysfunction. Alternative regimens for this setting
      are required. We describe 2 patients with newly diagnosed advanced aggressive
      lymphoma (diffuse large B-cell lymphoma [DLBCL] and classic Hodgkin lymphoma
      [HL]) presenting with severe hepatic dysfunction with hyperbilirubinemia (4.3
      13.2 mg/dL). Because of the inability to safely administer unattenuated doses of
      anthracycline-based regimens, dexamethasone, high-dose cytarabine, and cisplatin
      (DHAP) was used at full doses (along with rituximab for the DLBCL patient) until
      hepatic function normalized (1-5 cycles). The treatment was then converted to R
      CHOP (rituximab/cyclophosphamide/ doxorubicin/vincristine/prednisone) and ABVD
      (doxorubicin/bleomycin/vinblastine/dacarbazine) for the DLBCL and HL patient,
      respectively, to complete therapy. The patients had a partial remission and
      complete remission, respectively. These data suggest that DHAP is a safe and
      effective regimen that can be used without dose modification as part of initial
      therapy in the setting of aggressive lymphoma and hepatic failure. The literature
      on the use of treatment regimens for aggressive lymphoma in the setting of
      hepatic dysfunction is reviewed.

PMID- 19406730
TI  - Abstracts of the 13th Annual International Congress on Hematologic Malignancies.
      February 11-15, 2009. Whistler, British Columbia, Canada.

PMID- 19406731
TI  - Evidence on the effects of exercise therapy in the treatment of chronic disease.
AB  - Evidence on the effects of exercise in the treatment of patients with chronic
      diseases should be based on well designed randomised controlled trials. The most
      consistent finding of the meta-analyses summarised in the present work is that
      aerobic/functional capacity and muscle strength can be improved by exercise
      training among patients with different diseases without having detrimental
      effects on disease progression. This is important, as with population aging
      exercise therapy may be an important means of reducing disability and increasing
      the number of older people living independently. Additionally, there is
      accumulating evidence that in patients with chronic disease exercise therapy is
      effective in improving the prognostic risk factor profile and, in certain
      diseases, in delaying mortality. In some diseases, such as osteoarthritis, pain
      symptoms may also be reduced. Severe complications during the exercise therapy
      programs were rare.

PMID- 19406732
TI  - The development of a walkability index: application to the Neighborhood Quality
      of Life Study.
AB  - Emerging evidence supports a link between neighbourhood built environment and
      physical activity. Systematic methodologies for characterising neighbourhood
      built environment are needed that take advantage of available population
      information such as census-level demographics. Based on transportation and urban
      planning literatures, an integrated index for operationalising walkability using
      parcel-level information is proposed. Validity of the walkability index is
      examined through travel surveys among areas examined in the Neighborhood Quality
      of Life Study (NQLS), a study investigating built environment correlates of
      adults' physical activity.

PMID- 19406735
TI  - "So you think I'll survive?": a qualitative study about doctor-patient dialogues
      preceding high-risk cardiac surgery or intervention.
AB  - OBJECTIVE: To explore doctor-patient interactions and decision-making processes
      before high-risk cardiac surgery or intervention with special attention to
      existential challenges. DESIGN, SETTING AND PARTICIPANTS: We conducted a
      qualitative study with data drawn from doctor-patient dialogues preceding high
      risk procedures. The study setting was the cardiac department of a university
      hospital with 24-hour emergency service. We recruited a purposive sample of 10
      patients and eight doctors. The patients were categorised as high-risk patients
      in accordance with EuroSCORE and established angiographic procedural high-risk
      criteria. Transcripts from the dialogues were analysed with systematic text
      condensation, inspired by discourse analysis. MAIN OUTCOME MEASURE: Accounts of
      doctor-patient interaction reflecting existential aspects of the decision-making
      process. RESULTS: The main existential concerns identified in the doctor-patient
      interactions were surviving uncertainty, negotiating responsibility and trusting
      the doctor's proficiency. When handling uncertainty, doctors imparted complex
      information about risk, warnings and recommendations, while patients sought and
      trusted the doctors' advice. Though the decisions were made in asymmetrical power
      relations, they were based on a shared responsibility discussed and defined
      throughout the dialogues. The patients expressed a profound confidence in the
      doctor's ability to get them through the high-risk treatment and give the best
      help possible. CONCLUSIONS: Uncertainty, mortality, responsibility and trust are
      fundamental existential issues concerning both patients and doctors before high
      risk procedures, with an impact on decision-making processes. Increasing focus on
      underlying existential conditions, ethical reasoning and power relations in
      medical education may improve the quality of shared decision-making and informed
      consent related to high-risk treatment.

PMID- 19406733
TI  - Increased risk of adverse pregnancy outcomes in women with rheumatoid arthritis:
      a nationwide population-based study.
AB  - OBJECTIVE: Using a 3-year nationwide population-based database (2001-3), this
      study aims to examine the relationship between rheumatoid arthritis (RA) and
      adverse pregnancy outcomes. METHODS: The study used the Taiwan National Health
      Insurance Research Dataset and birth certificate registry. In total, 1912 mothers
      with RA and 9560 matched comparison mothers were included. Separate conditional
      logistic regression analyses were carried out to explore the risk of low
      birthweight (LBW), preterm births, small for gestational age (SGA) infants,
      preeclampsia and delivery mode (vaginal vs caesarean section (CS)) for the study
      and comparison groups. RESULTS: Regression analyses showed that the adjusted odds
      of LBW, SGA infants, preeclampsia and CS for women with RA were 1.47 (95% CI 1.22
      to 1.78), 1.20 (95% CI 1.05 to 1.38), 2.22 (95% CI 1.59 to 3.11) and 1.19 (95% CI
      1.07 to 1.31) times, respectively, that of comparison mothers. CONCLUSION: Women
      with RA had an increased risk of LBW, SGA babies, preeclampsia and CS compared
      with unaffected women.

PMID- 19406736
TI  - Relation between coronary atherosclerotic plaques and traditional risk factors in
      people with no history of cardiovascular disease undergoing multi-detector
      computed coronary angiography.
AB  - AIMS: To prospectively investigate the prevalence of coronary artery plaques
      (CAP) as detected by computed tomography-based angiography in a large number of
      consecutive individuals with no history of coronary artery disease (CAD) or acute
      coronary syndrome; to evaluate whether traditional risk factors are related to
      prevalence of CAP and to the expected 10-year risk of first major or fatal
      cardiovascular event (CVE). DESIGN: Prospective, single-centre, cross-sectional
      study. SETTING: The division of Cardiology at Fondazione Cardiocentro Ticino
      Lugano, Switzerland. METHODS: We prospectively included 920 consecutive
      individuals with no history of CAD who underwent computed tomography coronary
      angiography (CTCA). Risk estimation of fatal and non-fatal CVE was assessed using
      Global Assessment Risk (GAR) and Systematic Coronary Risk Evaluation (SCORE),
      respectively. Logistic regression was used to assess the association of risk
      factors with the prevalence of CAP. RESULTS: CAP was found in 459 (49.9%)
      individuals. Older age, higher body mass index, male gender, diabetes,
      hypertension and dyslipidaemia all increased the likelihood of the CAP burden at
      univariable analysis (p<0.001). At the multivariable analysis older age, male
      gender, hypertension and diabetes independently increased the likelihood of CAP
      burden (p<0.001). An increase in likelihood of CAP was observed in the presence
      of one, two and three or more risk factors and with an increasing value of GAR
      and SCORE. Notably, about 18% of subjects with CAP did not report any traditional
      risk factors and among individuals without CAPs, 12% had three or more risk
      factors. CONCLUSIONS: A direct relation between the prevalence of CAP, number of
      risk factors and the related 10-year risk of CVE was found. 18% of subjects
      without risk factors had CAP. In these individuals CTCA may help in further
      optimising the risk reduction strategies on an individual basis.

PMID- 19406737
TI  - Systemic bevacizumab (Avastin) therapy for exudative neovascular age-related
      macular degeneration. The BEAT-AMD-Study.
AB  - BACKGROUND: Double-blinded, randomised, prospective, pilot-study to determine the
      effect of systemic bevacizumab therapy. METHODS: Subjects with fibrovascular
      pigment epithelial detachment, subfoveal choroidal neovascularisation extending
      under the geometric centre of the foveal avascular zone and/or macular thickness
      of at least 300 microm in both eyes were included. Sixteen eyes were included and
      randomised equally to receive either three infusions of 5 mg/kg Avastin or 100 ml
      of 0.9% sodium chloride every 2 weeks. The main outcome measure was the lesion
      size. The follow-up time was 24 weeks. RESULTS: Throughout the 24-week follow-up,
      the lesion size and macular thickness decreased in the Avastin group by 0.5 (SD
      0.08) mm and 103.6 (14.9) microl respectively. In both groups, visual acuity
      remained stable in seven eyes and decreased in one eye. At the end of follow-up,
      50% of the eyes in the Avastin group became fibrotic, 37.5% remained unchanged,
      and 12.5% developed a subretinal bleeding. There was a treatable rise in blood
      pressure after Avastin treatment. CONCLUSION: Systemic Avastin could be offered
      to patients with exudative age-related macular degeneration in both eyes and/or
      patients who refuse intravitreal injections if blood pressure is normal and there
      is no history of thrombosis.

PMID- 19406738
TI  - Can we rely on one laboratory test in detection of extended-spectrum beta
      lactamases among Enterobacteriaceae? An evaluation of the Vitek 2 system and
      comparison with four other detection methods in Kuwait.
AB  - BACKGROUND AND AIMS: Clinical hospitals need to correctly identify extended
      spectrum beta-lactamase (ESBL)-producing bacteria in infected patients to
      correctly treat the patient and avoid spreading antibiotic resistance. Kuwaiti
      hospitals use one laboratory test for detecting ESBL bacteria. This study
      evaluated whether that was sufficient to detect ESBL bacteria, and compared the
      Vitek system with other detection systems. METHODS: (Klebsiella pneumoniae,
      Escherichia coli, K oxytoca and Enterobacter cloacae) were collected from five
      different Kuwaiti main hospitals, all of which were flagged as ESBL-positive by
      the Vitek 2 system. The isolates were retested by the Vitek 2 system, and were
      also tested by double disc diffusion (DDD), the disc approximation test, the E
      test and the MicroScan system for the detection of ESBLs. RESULTS: Retesting with
      the Vitek system revealed 100% compatibility with the results of the source
      hospitals. The MicroScan system, DDD, disc approximation test and E-test could
      detect ESBL in 199, 192, 178 and 205 isolates, respectively. CONCLUSIONS:
      Technically, the MicroScan and Vitek 2 systems were the least demanding method to
      detect ESBL as it is an integral part of the routine susceptibility test card. E
      test strips were reliable but the most expensive of all techniques used. The DDD
      test and disc approximation, while relatively inexpensive, were technically
      subjective. The Vitek system may be very suitable in clinical laboratories, but
      would be better if accompanied with another test for detection of ESBL bacteria.

PMID- 19406739
TI  - Evaluation of replacing the existing diagnostic strategy for Neisseria
      gonorrhoeae and Chlamydia trachomatis infections with sole molecular testing of
      urine specimens in a sexually transmitted infection clinic setting.
AB  - OBJECTIVES: To evaluate nucleic acid testing of urine specimens against
      conventional Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) tests in
      genital swab specimens in a sexually transmitted infection (STI) clinic setting.
      METHODS: Genital swab and urine samples were collected from attendees of public
      STI clinics in Hong Kong from May to June 2007. Swab specimens were subjected to
      on-site Gram stained microscopy and inoculation onto modified Thayer-Martin
      medium for NG culture before laboratory processing. CT PCR on genital swabs was
      performed by the Roche Cobas Amplicor test. Urine samples were tested for CT and
      NG by the Aptima Combo 2 (AC2) assay. RESULTS: Data from 414 patients were
      analysed. The sensitivity and specificity of AC2 for NG were 100% (35/35) and
      98.4% (373/379), respectively, with culture of genital swab specimens as
      standard. On-site microscopy provided timely results for empirical antimicrobial
      therapy, whereas culture yielded bacterial isolates for susceptibility testing
      and typing studies. Regarding CT, using Amplicor on genital swab specimens as
      reference, the sensitivity and specificity of AC2 were 98.7% (78/79) and 97.5%
      (313/321), respectively. Amplicor yielded uninterpretable results in 14 specimens
      due to PCR inhibitors. CONCLUSIONS: The current STI clinic and laboratory
      practices were practical and useful for clinical management, even though
      favourable results were obtained with the AC2 assay, which had streamlined
      laboratory workflow. The use of a molecular testing strategy may be cost
      effective with microscopy and culture being targetted for patient groups with the
      highest expected yield of positive results.

PMID- 19406740
TI  - Long-term wine consumption is related to cardiovascular mortality and life
      expectancy independently of moderate alcohol intake: the Zutphen Study.
AB  - BACKGROUND: Light to moderate alcohol intake lowers the risk of cardiovascular
      mortality, but whether this protective effect can be attributed to a specific
      type of beverage remains unclear. Moreover, little is known about the effects of
      long-term alcohol intake on life expectancy. METHODS: The impact of long-term
      alcohol intake and types of alcoholic beverages consumed on cardiovascular
      mortality and life expectancy at age 50 was investigated in the Zutphen Study, a
      cohort of 1373 men born between 1900 and 1920 and examined repeatedly between
      1960 and 2000. Hazard ratios (HRs) for total alcohol intake and alcohol from
      wine, beer and spirits were obtained from time-dependent Cox regression models.
      Life expectancy at age 50 was calculated from areas under survival curves.
      RESULTS: Long-term light alcohol intake, that is < or =20 g per day, compared
      with no alcohol, was strongly and inversely associated with cerebrovascular (HR
      0.43, 95% CI 0.26 to 0.70), total cardiovascular (HR 0.70, 95% CI 0.55 to 0.89)
      and all-cause mortality (HR 0.75, 95% CI 0.63 to 0.91). Independent of total
      alcohol intake, long-term wine consumption of, on average, less than half a glass
      per day was strongly and inversely associated with coronary heart disease (HR
      0.61, 95% CI 0.41 to 0.89), total cardiovascular (HR 0.68, 95% CI 0.53 to 0.86)
      and all-cause mortality (HR 0.73, 95% CI 0.62 to 0.87). These results could not
      be explained by differences in socioeconomic status. Life expectancy was about 5
      years longer in men who consumed wine compared with those who did not use
      alcoholic beverages. CONCLUSION: Long-term light alcohol intake lowered
      cardiovascular and all-cause mortality risk and increased life expectancy. Light
      wine consumption was associated with 5 years longer life expectancy; however,
      more studies are needed to verify this result.

PMID- 19406742
TI  - Is the wealth index a proxy for consumption expenditure? A systematic review.
AB  - BACKGROUND: Many epidemiological studies require a measure of socioeconomic
      position. The monetary measure preferred by economists is consumption
      expenditure; the wealth index has been proposed as a reliable, simple alternative
      to expenditure and is extensively used. METHODS: A systematic review was
      conducted of the agreement between wealth indices and consumption expenditure,
      summarising the agreement and exploring factors affecting agreement. RESULTS:
      Seventeen studies using 36 datasets met the inclusion criteria. Of these, 22
      demonstrated weak agreement, 10 moderate agreement, and four strong agreement.
      There was some evidence that agreement is higher: in middle-income settings; in
      urban areas; for wealth indices with a greater number of indicators; and for
      wealth indices including a wider range of indicators. CONCLUSIONS: The wealth
      index is mostly a poor proxy for consumption expenditure.

PMID- 19406743
TI  - Socioeconomic position and hypertension: a study of urban civil servants in
      Ghana.
AB  - BACKGROUND: The association of socioeconomic position and cardiovascular disease
      risk factors in low- and middle-income countries has not been as consistent as
      that reported from high-income countries. METHODS: A cross-sectional study of
      1015 participants from seven civil service departments in Accra, Ghana, was
      conducted in 2006. Hypertension was diagnosed when the mean of a second and third
      blood pressure reading on each of two visits 3 weeks apart was > or =140/90 mmHg
      or where participants were already diagnosed and on antihypertensive drugs.
      Socioeconomic measures considered were education, early life and adult wealth and
      civil service employment grade. RESULTS: The age-adjusted prevalence of
      hypertension was lowest in participants of lower socioeconomic position (OR
      21.9%; 95% CI 16.3 to 27.5) and highest in those of highest socioeconomic
      position (OR 31.8%; 95% CI 23.4 to 40.2) with inconsistent patterns among
      participants in the intermediate socioeconomic groups. Participants in the
      highest employment grade category were more likely to have hypertension than
      those in the lowest category (OR 1.91; 95% CI 1.14 to 3.20). There was a positive
      graded association between adult wealth and hypertension, with more assets
      associated with a greater risk (p trend 0.008). This trend was partly explained
      by body mass index differences. Blood pressure control among those with diagnosed
      hypertension was generally poor across the socioeconomic strata. CONCLUSIONS: In
      low-income countries such as Ghana, there is a need to promote primary prevention
      of hypertension across the socioeconomic strata, with a focus on weight control
      among civil servants of higher socioeconomic position, and better hypertension
      control in those with hypertension.

PMID- 19406741
TI  - Socioeconomic position and cognitive decline using data from two waves: what is
      the role of the wave 1 cognitive measure?
AB  - BACKGROUND: Analysis of change in health status using data from two waves can be
      examined either adjusted or unadjusted for baseline health status. The effect of
      socioeconomic position (SEP) on cognitive change was assessed using both these
      strategies and the implications of the analyses are discussed. METHODS: Data from
      1261 men and 483 women of the Whitehall II cohort study, aged 50-55 years at wave
      1, were used. Cognition was assessed at both waves using a test of verbal memory,
      and two tests of verbal fluency. Analysis of variance (ANOVA) was used to
      estimate the effect of SEP on change score and analysis of covariance (ANCOVA)
      was used to estimate this effect adjusted for the baseline cognitive score. The
      ANCOVA estimates were corrected for bias due to measurement error (estimated
      based on 3-month test-retest). Finally, ANCOVA estimates were examined for
      increasing levels of measurement error. RESULTS: The results of the ANOVA suggest
      no effect of SEP on cognitive decline. In contrast, the ANCOVA suggests
      significantly greater cognitive decline in the lower SEP groups. However, the
      ANCOVA estimates for the effect of wave 1 cognition show evidence for regression
      to the mean due to the presence of measurement error. The corrected ANCOVA
      estimates show no association between SEP and cognitive decline. CONCLUSIONS:
      Results from analysis of change using two waves of observational data, when
      adjusted for baseline, should be interpreted with caution.

PMID- 19406744
TI  - Combined extracellular matrix cross-linking activity of the peroxidase MLT-7 and
      the dual oxidase BLI-3 is critical for post-embryonic viability in Caenorhabditis
      elegans.
AB  - The nematode cuticle is a protective collagenous extracellular matrix that is
      modified, cross-linked, and processed by a number of key enzymes. This Ecdysozoan
      specific structure is synthesized repeatedly and allows growth and development in
      a linked degradative and biosynthetic process known as molting. A targeted RNA
      interference screen using a cuticle collagen marker has been employed to identify
      components of the cuticle biosynthetic pathway. We have characterized an
      essential peroxidase, MoLT-7 (MLT-7), that is responsible for proper cuticle
      molting and re-synthesis. MLT-7 is an active, inhibitable peroxidase that is
      expressed in the cuticle-synthesizing hypodermis coincident with each larval
      molt. mlt-7 mutants show a range of body morphology defects, most notably molt,
      dumpy, and early larval stage arrest phenotypes that can all be complemented with
      a wild type copy of mlt-7. The cuticles of these mutants lacks di-tyrosine cross
      links, becomes permeable to dye and accessible to tyrosine iodination, and have
      aberrant collagen protein expression patterns. Overexpression of MLT-7 causes
      mutant phenotypes further supporting its proposed enzymatic role. In combination
      with BLI-3, an H2O2-generating NADPH dual oxidase, MLT-7 is essential for post
      embryonic development. Disruption of mlt-7, and particularly bli-3, via RNA
      interference also causes dramatic changes to the in vivo cross-linking patterns
      of the cuticle collagens DPY-13 and COL-12. This points toward a functionally
      cooperative relationship for these two hypodermally expressed proteins that is
      essential for collagen cross-linking and proper extracellular matrix formation.

PMID- 19406745
TI  - Crystal structure of a fibroblast growth factor homologous factor (FHF) defines a
      conserved surface on FHFs for binding and modulation of voltage-gated sodium
      channels.
AB  - Voltage-gated sodium channels (Nav) produce sodium currents that underlie the
      initiation and propagation of action potentials in nerve and muscle cells.
      Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C
      terminal region of the Nav alpha subunit to modulate fast inactivation of the
      channel. In this study we solved the crystal structure of a 149-residue-long
      fragment of human FHF2A which unveils the structural features of the homology
      core domain of all 10 human FHF isoforms. Through analysis of crystal packing
      contacts and site-directed mutagenesis experiments we identified a conserved
      surface on the FHF core domain that mediates channel binding in vitro and in
      vivo. Mutations at this channel binding surface impaired the ability of FHFs to
      co-localize with Navs at the axon initial segment of hippocampal neurons. The
      mutations also disabled FHF modulation of voltage-dependent fast inactivation of
      sodium channels in neuronal cells. Based on our data, we propose that FHFs
      constitute auxiliary subunits for Navs.

PMID- 19406746
TI  - Kinome siRNA screen identifies SMG-1 as a negative regulator of hypoxia-inducible
      factor-1alpha in hypoxia.
AB  - Hypoxia-inducible factor-1 (HIF-1) plays a central role in tumor progression by
      regulating genes involved in proliferation, glycolysis, angiogenesis, and
      metastasis. To improve our understanding of HIF-1 regulation by kinome, we
      screened a kinase-specific small interference RNA library using a hypoxia
      response element (HRE) luciferase reporter assay under hypoxic conditions. This
      screen determined that depletion of cellular SMG-1 kinase most significantly
      modified cellular HIF-1 activity in hypoxia. SMG-1 is the newest and least
      studied member of the phosphoinositide 3-kinase-related kinase family, which
      consists of ATM, ATR, DNA-PKcs, mTOR, and SMG-1. We individually depleted members
      of the phosphoinositide 3-kinase-related kinase family, and only SMG-1 deficiency
      significantly augmented HIF-1 activity in hypoxia. We subsequently discovered
      that SMG-1 kinase activity was activated by hypoxia, and depletion of SMG-1 up
      regulated MAPK activity under low oxygen. Suppressing cellular MAPK by silencing
      ERK1/2 or by treatment with U0126, a MAPK inhibitor, partially blocked the
      escalation of HIF-1 activity resulting from SMG-1 deficiency in hypoxic cells.
      Increased expression of SMG-1 but not kinase-dead SMG-1 effectively inhibited the
      activity of HIF-1alpha. In addition, cellular SMG-1 deficiency increased
      secretion of the HIF-1alpha-regulated angiogenic factor, vascular epidermal
      growth factor, and survival factor, carbonic anhydrase IX (CA9), as well as
      promoted the hypoxic cell motility. Taken together, we discovered that SMG-1
      negatively regulated HIF-1alpha activity in hypoxia, in part through blocking
      MAPK activation.

PMID- 19406747
TI  - Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric
      a{beta}.
AB  - Accumulation of amyloid beta (Abeta) oligomers in the brain is toxic to synapses
      and may play an important role in memory loss in Alzheimer disease. However, how
      these toxins are built up in the brain is not understood. In this study we
      investigate whether impairments of insulin and insulin-like growth factor-1 (IGF
      1) receptors play a role in aggregation of Abeta. Using primary neuronal culture
      and immortal cell line models, we show that expression of normal insulin or IGF-1
      receptors confers cells with abilities to reduce exogenously applied Abeta
      oligomers (also known as ADDLs) to monomers. In contrast, transfection of
      malfunctioning human insulin receptor mutants, identified originally from patient
      with insulin resistance syndrome, or inhibition of insulin and IGF-1 receptors
      via pharmacological reagents increases ADDL levels by exacerbating their
      aggregation. In healthy cells, activation of insulin and IGF-1 receptor reduces
      the extracellular ADDLs applied to cells via seemingly the insulin-degrading
      enzyme activity. Although insulin triggers ADDL internalization, IGF-1 appears to
      keep ADDLs on the cell surface. Nevertheless, both insulin and IGF-1 reduce ADDL
      binding, protect synapses from ADDL synaptotoxic effects, and prevent the ADDL
      induced surface insulin receptor loss. Our results suggest that dysfunctions of
      brain insulin and IGF-1 receptors contribute to Abeta aggregation and subsequent
      synaptic loss.

PMID- 19406748
TI  - Transforming growth factor-beta promotes recruitment of bone marrow cells and
      bone marrow-derived mesenchymal stem cells through stimulation of MCP-1
      production in vascular smooth muscle cells.
AB  - Bone marrow-derived progenitor cells have recently been shown to be involved in
      the development of intimal hyperplasia after vascular injury. Transforming growth
      factor-beta (TGF-beta) has profound stimulatory effects on intimal hyperplasia,
      but it is unknown whether these effects involve progenitor cell recruitment. In
      this study we found that although TGF-beta had no direct effect on progenitor
      cell recruitment, conditioned media derived from vascular smooth muscle cells
      (VSMC) stimulated with TGF-beta induced migration of both total bone marrow (BM)
      cells and BM-mesenchymal stem cells (MSC) and also induced MSC differentiation
      into smooth muscle like cells. Furthermore, overexpression of the signaling
      molecule Smad3 in VSMC via adenovirus-mediated gene transfer (AdSmad3) enhanced
      the TGF-beta's chemotactic effect. Microarray analysis of VSMC stimulated by TGF
      beta/AdSmad3 revealed monocyte chemoattractant protein-1 (MCP-1) as a likely
      factor responsible for progenitor cell recruitment. We then demonstrated that TGF
      beta through Smad3 phosphorylation induced a robust expression of MCP-1 in VSMC.
      Recombinant MCP-1 mimicked the stimulatory effect of conditioned media on BM and
      MSC migration. In the rat carotid injury model, Smad3 overexpression
      significantly increased MCP-1 expression after vascular injury, consistent with
      our in vitro results. Interestingly, TGF-beta/Smad3-induced MCP-1 was completely
      blocked by both Ro-32-0432 and rotterlin, suggesting protein kinase C-delta
      (PKCdelta) may play a role in TGF-beta/Smad3-induced MCP-1 expression. In
      summary, our data demonstrate that TGF-beta, through Smad3 and PKCdelta,
      stimulates VSMC production of MCP-1, which is a chemoattractant for bone marrow
      derived cells, specifically MSC. Manipulation of this signaling system may
      provide a novel approach to inhibition of intimal hyperplasia.

PMID- 19406749
TI  - Phosphorylation of alpha6-tubulin by protein kinase Calpha activates motility of
      human breast cells.
AB  - Engineered overexpression of protein kinase Calpha (PKCalpha) was previously
      shown to endow nonmotile MCF-10A human breast cells with aggressive motility. A
      traceable mutant of PKCalpha (Abeyweera, T. P., and Rotenberg, S. A. (2007)
      Biochemistry 46, 2364-2370) revealed that alpha6-tubulin is phosphorylated in
      cells expressing traceable PKCalpha and in vitro by wild type PKCalpha. Gain-of
      function, single site mutations (Ser-->Asp) were constructed at each PKC
      consensus site in alpha6-tubulin (Ser158, Ser165, Ser241, and Thr337) to simulate
      phosphorylation. Following expression of each construct in MCF-10A cells,
      motility assays identified Ser165 as the only site in alpha6-tubulin whose
      pseudophosphorylation reproduced the motile behavior engendered by PKCalpha.
      Expression of a phosphorylation-resistant mutant (S165N-alpha6-tubulin) resulted
      in suppression of MCF-10A cell motility stimulated either by expression of
      PKCalpha or by treatment with PKCalpha-selective activator diacylglycerol
      lactone. MCF-10A cells treated with diacylglycerol-lactone showed strong
      phosphorylation of endogenous alpha-tubulin that could be blocked when S165N
      alpha6-tubulin was expressed. The S165N mutant also inhibited intrinsically
      motile human breast tumor cells that express high endogenous PKCalpha levels (MDA
      MB-231 cells) or lack PKCalpha and other conventional isoforms (MDA-MB-468
      cells). Comparison of Myc-tagged wild type alpha6-tubulin and S165N-alpha6
      tubulin expressed in MDA-MB-468 cells demonstrated that Ser165 is also a major
      site of phosphorylation for endogenously active, nonconventional PKC isoforms.
      PKC-stimulated motility of MCF-10A cells was nocodazole-sensitive, thereby
      implicating microtubule elongation in the mechanism. These findings support a
      model in which PKC phosphorylates alpha-tubulin at Ser165, leading to microtubule
      elongation and motility.

PMID- 19406751
TI  - Three novel variants in X-linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy is an inherited neurological disorder caused by
      mutations in the ABCD1 gene (located on chromosome Xq28) encoding
      adrenoleukodystrophy protein which is involved in the transport of substrates
      from the cytoplasm into the peroxisomal lumen. There is a scarcity of reports on
      mutation analysis of X-linked adrenoleukodystrophy from India. Here, we report 3
      novel variants (c.67_83del17, c.395G>A, c.1938_1939dupGG) in 3 unrelated Indian
      families.

PMID- 19406750
TI  - Smooth muscle archvillin is an ERK scaffolding protein.
AB  - ERK influences a number of pathways in all cells, but how ERK activities are
      segregated between different pathways has not been entirely clear. Using
      immunoprecipitation and pulldown experiments with domain-specific recombinant
      fragments, we show that smooth muscle archvillin (SmAV) binds ERK and members of
      the ERK signaling cascade in a domain-specific, stimulus-dependent, and pathway
      specific manner. MEK binds specifically to the first 445 residues of SmAV. B-Raf,
      an upstream regulator of MEK, constitutively interacts with residues 1-445 and
      446-1250. Both ERK and 14-3-3 bind to both fragments, but in a stimulus-specific
      manner. Phosphorylated ERK is associated only with residues 1-445. An ERK
      phosphorylation site was determined by mass spectrometry to reside at Ser132. A
      phospho-antibody raised to this site shows that the site is phosphorylated during
      alpha-agonist-mediated ERK activation in smooth muscle tissue. Phosphorylation of
      SmAV by ERK decreases the association of phospho-ERK with SmAV. These results,
      combined with previous observations, indicate that SmAV serves as a new ERK
      scaffolding protein and provide a mechanism for regulation of ERK binding,
      activation, and release from the signaling complex.

PMID- 19406752
TI  - MELAS with A3243G mutation presenting with occipital status epilepticus.
AB  - Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
      (MELAS) is a mitochondrial disorder commonly caused by the A3243G mutation. We
      report a patient who initially presented with visual hallucinations, headaches,
      and nonconvulsive status epilepticus originating in left occipital lobe who
      subsequently progressed to have multifocal seizures. His magnetic resonance
      imaging (MRI) showed subtle T2 hyperintensity at first presentation that
      subsequently fully resolved. He then had more typical diffusion restriction not
      conforming to vascular territories. Evolution of his neuroimaging and
      electroencephalogram (EEG) is discussed with a brief review of literature.
      Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes should
      be suspected early with occipital lobe seizures.

PMID- 19406754
TI  - The relationship between medical impairments and arithmetic development in
      children with cerebral palsy.
AB  - Arithmetic ability was tested in children with cerebral palsy without severe
      intellectual impairment (verbal IQ >or= 70) attending special (n = 41) or
      mainstream education (n = 16) as well as control children in mainstream education
      (n = 16) throughout first and second grade. Children with cerebral palsy in
      special education did not appear to have fully automatized arithmetic facts by
      the end of second grade. Their lower accuracy and consistently slower (verbal)
      response times raise important concerns for their future arithmetic development.
      Differences in arithmetic performance between children with cerebral palsy in
      special or mainstream education were not related to localization of cerebral
      palsy or to gross motor impairment. Rather, lower accuracy and slower verbal
      responses were related to differences in nonverbal intelligence and the presence
      of epilepsy. Left-hand impairment was related to slower verbal responses but not
      to lower accuracy.

PMID- 19406753
TI  - Porphyrin-based photocatalytic nanolithography: a new fabrication tool for
      protein arrays.
AB  - Nanoarray fabrication is a multidisciplinary endeavor encompassing materials
      science, chemical engineering, and biology. We formed nanoarrays via a new
      technique, porphyrin-based photocatalytic nanolithography. The nanoarrays, with
      controlled features as small as 200 nm, exhibited regularly ordered patterns and
      may be appropriate for (a) rapid and parallel proteomics screening of immobilized
      biomolecules, (b) protein-protein interactions, and/or (c) biophysical and
      molecular biology studies involving spatially dictated ligand placement. We
      demonstrated protein immobilization utilizing nanoarrays fabricated via
      photocatalytic nanolithography on silicon substrates where the immobilized
      proteins are surrounded by a non-fouling polymer background.

PMID- 19406755
TI  - Headache in a national sample of American children: prevalence and comorbidity.
AB  - The purpose of this study was to determine the prevalence, sociodemographic
      correlates, and comorbidity of recurrent headache in children in the United
      States. Participants were individuals aged 4 to 18 years (n = 10,198) who
      participated in the National Health and Nutrition Examination Surveys. Data on
      recurrent and other health conditions were analyzed. Frequent or severe headaches
      including migraine in the past 12 months were reported in 17.1% of children.
      Asthma, hay fever, and frequent ear infections were more common in children with
      headache, with at least 1 of these occurring in 41.6% of children with headache
      versus 25.0% of children free of headache. Other medical problems associated with
      childhood headaches include anemia, overweight, abdominal illnesses, and early
      menarche. Recurrent headache in childhood is common and has significant medical
      comorbidity. Further research is needed to understand biologic mechanisms and
      identify more homogeneous subgroups in clinical and genetic studies.

PMID- 19406756
TI  - Adolescent and caregiver experiences with epilepsy.
AB  - Epilepsy during adolescence can impede the development of psychosocial
      independence and typical biological maturational processes. We examined in
      parallel the experiences and perceptions of adolescent patients with epilepsy and
      their caregivers. Specifically, we focused on frequency and type of seizures,
      comorbid conditions, adherence to therapies, productivity, clinical and quality
      of life consequences of seizures, estimated use and content of seizure emergency
      plans, and the patient-physician relationship. Two cross-sectional online surveys
      were conducted among 153 adolescent patients with epilepsy and their respective
      caregivers. A total of 35% of adolescents indicated that they had been
      nonadherent to antiepileptic medications in the prior month. Adolescents scored
      significantly lower compared with their peers on quality-of-life measures.
      Adolescents and caregivers reported similarly on nearly all domains. An
      adolescent-centered epilepsy management program may help alleviate concerns and
      also help the adolescent independently manage their epilepsy as they transition
      into adulthood.

PMID- 19406757
TI  - Decreased seizure activity in a human neonate treated with bumetanide, an
      inhibitor of the Na(+)-K(+)-2Cl(-) cotransporter NKCC1.
AB  - Neonatal seizures have devastating consequences for brain development and are
      inadequately treated by available antiepileptics. In neonates, gamma-aminobutyric
      acid (GABA) is an excitatory neurotransmitter due to elevated levels of
      intraneuronal chloride achieved by robust activity of the Na(+)-K(+)-2Cl( -)
      cotransporter (NKCC1). This depolarizing action of GABA likely contributes to the
      lowered seizure threshold, increased seizure propensity, and poor efficacy of
      GABAergic anticonvulsants among infants. The diuretic bumetanide inhibits NKCC1
      and silences seizure activity in rodent models of neonatal seizures, but its
      effect on seizures in human neonates is unknown. Continuous
      electroencephalography (EEG) monitoring was used to quantify the number,
      duration, and frequency of seizures 2 hours before and after the administration
      of bumetanide in a neonate with intractable multifocal seizures. Significant
      reductions in mean seizure duration and frequency were noted following treatment,
      with no associated clinical side effects or metabolic imbalances. These results
      suggest bumetanide may exert antiepileptic effects in human neonates.

PMID- 19406758
TI  - Juvenile myasthenia gravis: three case reports and a literature review.
AB  - Juvenile myasthenia gravis is a rare disorder acquired in childhood, representing
      10% to 15% of all cases of myasthenia gravis. Like the adult form, it is
      generally characterized by an autoimmune attack on acetylcholine receptors at the
      neuromuscular junction. Most patients present with ptosis, diplopia, and
      fatigability. More advanced cases may also have bulbar problems and limb
      weakness. Left untreated, the disease may progress to paralysis of the
      respiratory muscles. Early recognition of this disease helps avoid unnecessary
      testing, prevent undue parental anxiety, and stop the progression of symptoms.
      Here, we relate the clinical course and current status of 3 patients with
      juvenile myasthenia gravis, discuss the disease in general, and review current
      treatment modalities.

PMID- 19406759
TI  - Ocular myasthenia gravis and Graves disease in a 10-year-old child.
AB  - We report the association between myasthenia gravis and Graves disease in a 10
      year-old boy and discuss the important aspects of both diseases, the importance
      of recognizing the association, and the investigations of choice to distinguish
      the 2 disorders. Early diagnosis of the 2 disorders may help in effective
      treatment institution with more rapid treatment responses with a possible
      improvement in prognosis and clinical course. Resolution of myasthenia gravis is
      not expected until the euthyroid state is restored. We recommend complete thyroid
      status review on all patients presenting with ocular myasthenia gravis.

PMID- 19406760
TI  - Unilateral palatal and abducens palsy in childhood hepatitis A virus infection.
AB  - Isolated cranial nerve paresis in childhood hepatitis A virus infection is rare.
      The authors report an instance of concomitant right-hand side palatal and
      abducens palsy, developing in the course of an otherwise uncomplicated hepatitis
      A virus infection in a 5-year-old girl. The neurological complications were
      transient, and she recovered completely with supportive therapy.

PMID- 19406762
TI  - Transcranial direct current stimulation: a novel approach to control hyperphagia
      in Prader-Willi syndrome.

PMID- 19406764
TI  - Coils and cash: what coil vendors don't want you to know.

PMID- 19406766
TI  - Quantitative hemodynamic analysis of brain aneurysms at different locations.
AB  - BACKGROUND AND PURPOSE: Studies have shown that the occurrence of brain aneurysms
      and risk of rupture vary between locations. However, the reason that aneurysms at
      different branches of the cerebral arteries have different clinical presentations
      is not clear. Because research has indicated that aneurysm hemodynamics may be
      one of the important factors related to aneurysm growth and rupture, our aim was
      to analyze and compare the flow parameters in aneurysms at different locations.
      MATERIALS AND METHODS: A total of 24 patient-specific aneurysm models were
      constructed by using 3D rotational angiographic data for the hemodynamic
      simulation. Previously developed computational fluid dynamics software was
      applied to each aneurysm to simulate the blood-flow properties. Hemodynamic data
      at peak pulsatile flow were recorded, and wall shear stress (WSS) and flow rate
      in the aneurysms and parent arteries were quantitatively compared. To validate
      our method, a comparison with a previously reported technique was also performed.
      RESULTS: WSS and flow rate in the aneurysms at the peak of the cardiac cycle were
      found to differ in magnitude between different locations. Multiple comparisons
      among locations showed higher WSS and flow rate in middle cerebral artery
      aneurysms and lower WSS and flow rate in basilar artery and anterior
      communicating artery aneurysms. CONCLUSIONS: We observed changes in hemodynamic
      values that may be related to aneurysm location. Further study of aneurysm
      locations with a large number of cases is needed to test this hypothesis.

PMID- 19406765
TI  - Tissue-specific imaging is a robust methodology to differentiate in vivo T1 black
      holes with advanced multiple sclerosis-induced damage.
AB  - BACKGROUND AND PURPOSE: Brains of patients with multiple sclerosis (MS)
      characteristically have "black holes" (BHs), hypointense lesions on T1-weighted
      (T1W) spin-echo (SE) images. Although conventional MR imaging can disclose
      chronic BHs (CBHs), it cannot stage the degree of their pathologic condition.
      Tissue-specific imaging (TSI), a recently introduced MR imaging technique, allows
      selective visualization of white matter (WM), gray matter (GM), and CSF on the
      basis of T1 values of classes of tissue. We investigated the ability of TSI-CSF
      to separate CBHs with longer T1 values, which likely represent lesions containing
      higher levels of destruction and unbound water. MATERIALS AND METHODS: Eighteen
      patients with MS, who had already undergone MR imaging twice (24 months apart) on
      a 1.5T scanner, underwent a 3T MR imaging examination. Images acquired at 1.5T
      included sequences of precontrast and postcontrast T1W SE, T2-weighted (T2W) SE,
      and magnetization transfer (MT). Sequences obtained at 3T included precontrast
      and postcontrast T1W SE, T2W SE, T1 inversion recovery prepared fast spoiled
      gradient recalled-echo (IR-FSPGR) and TSI. A BH on the 3T-IR-FSPGR was defined as
      a CBH if seen as a hypointense, nonenhancing lesion with a corresponding T2
      abnormality for at least 24 months. CBHs were separated into 2 groups: those
      visible as hyperintensities on TSI-CSF (group A), and those not appearing on the
      TSI-CSF (group B). RESULTS: Mean MT ratios of group-A lesions (0.22 +/- 0.06,
      0.13-0.35) were lower (F(1,13) = 60.39; P < .0001) than those of group-B lesions
      (0.32 +/- 0.03, 0.27-0.36). CONCLUSIONS: Group-A lesions had more advanced tissue
      damage; thus, TSI is a potentially valuable method for qualitative and objective
      identification.

PMID- 19406767
TI  - CT angiography for brain death diagnosis.
AB  - BACKGROUND AND PURPOSE: Lack of cerebral circulation is an important confirmatory
      test for brain death (BD). Conventional angiography remains the standard imaging
      method, but CT angiography (CTA) is emerging as an alternative. France accepts BD
      diagnoses relying on a score based on lack of opacification of 7 intracerebral
      vessels in CTA images. The purpose of this study was to validate the efficiency
      of this score and to evaluate the sensitivity of a novel 4-point CTA score in
      confirming BD. MATERIALS AND METHODS: A prospective multicentric study was
      conducted during 12 months with 105 patients referred for CTA to confirm a
      clinical diagnosis of BD. Clinical data were recorded. CTA images were
      interpreted first by local radiologists at the referent center, resulting in a 7
      point score based on lack of opacification of the pericallosal and cortical
      segments of the middle cerebral arteries (MCAs), internal cerebral veins (ICVs),
      and 1 great cerebral vein per patient and, second, by a consensus panel of 3
      expert radiologists, blinded to the initial scores, resulting in novel 4-point
      scores based on the lack of opacification of the cortical segments of the MCAs
      and ICVs. RESULTS: Injection of contrast medium did not alter renal function.
      With the initial 7-point score, sensitivity was 62.8%. With the simplified 4
      point score, sensitivity was 85.7% and specificity was 100%. Opacification of
      ICVs was absent in 98.1% of patients. CONCLUSIONS: Lack of opacification in the
      cortical segments of the MCAs and internal veins in CTA is efficient and reliable
      for confirming BD.

PMID- 19406770
TI  - Methanosphaerula palustris gen. nov., sp. nov., a hydrogenotrophic methanogen
      isolated from a minerotrophic fen peatland.
AB  - Peatlands are important sources of CH(4) emissions to the atmosphere and
      molecular surveys have identified a diverse, but mainly uncultured, euryarchaeal
      community in them. Characterization of a strain, E1-9c(T), associated with
      uncultured group E1, from a minerotrophic fen is reported. Cells were regular
      cocci, usually found in pairs, that stained Gram-positive and were resistant to
      lysis by 0.1 % SDS. Multiple flagella were observed, but motility was not
      observed in wet mounts. Optimal growth was obtained at moderate temperatures (28
      30 degrees C) and slightly acidic pH (5.5). Total Na(+) and NaCl were only
      tolerated at concentrations less than 100 mM and 0.5 %, respectively, and Na(2)S
      concentrations above 0.1 mM were inhibitory. H(2)/CO(2) and formate were the only
      methanogenic substrates used by E1-9c(T); formate concentrations above 50 mM were
      inhibitory for growth. Vitamins, coenzyme M and acetate (4 mM) were required for
      growth and the doubling time was about 19 h. Phylogenetic analysis of the 16S
      rRNA gene and inferred McrA amino acid sequences showed that E1-9c(T) represented
      an independent lineage within the order Methanomicrobiales. Physiological and
      phylogenetic comparisons with different members of the order supported
      classification of E1-9c(T) in a new genus in the Methanomicrobiales. The name
      Methanosphaerula palustris gen. nov., sp. nov. is proposed; strain E1-9c(T)
      (=ATCC BAA-1565(T) =DSM 19958(T)) is the type strain of Methanosphaerula
      palustris.

PMID- 19406771
TI  - Desulfovibrio marrakechensis sp. nov., a 1,4-tyrosol-oxidizing, sulfate-reducing
      bacterium isolated from olive mill wastewater.
AB  - A novel mesophilic sulfate-reducing bacterium, EMSSDQ(4)(T), was isolated from
      olive mill wastewater in the semi-arid region of Morocco (Marrakech). Cells were
      Gram-negative, catalase-positive, straight rods that were non-motile and non
      spore-forming and contained cytochrome c(3) and desulfoviridin. The DNA G+C
      content was 65.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences
      revealed that the isolate was a member of the genus Desulfovibrio with
      Desulfovibrio carbinoliphilus D41(T), Desulfovibrio alcoholivorans SPSN(T),
      Desulfovibrio fructosivorans JJ(T) and Desulfovibrio carbinolicus EDK82(T) as the
      most closely related strains with validly published names. In addition to the
      classical substrates used by Desulfovibrio species, the isolate oxidized 1,4
      tyrosol, one of the most abundant phenolic compounds occurring in olive mill
      wastewater, to 4-hydroxyphenylacetate without ring cleavage. D. alcoholivorans
      SPSN(T) was also found to carry out this reaction. Under air, strain EMSSDQ(4)(T)
      exhibited limited growth on lactate and yeast extract in the absence of sulfate.
      On the basis of genotypic and phenotypic characteristics, it is proposed that the
      isolate represents a novel species, Desulfovibrio marrakechensis sp. nov. The
      type strain is EMSSDQ(4)(T) (=DSM 19337(T) =ATCC BAA-1562(T)).

PMID- 19406772
TI  - Leuconostoc palmae sp. nov., a novel lactic acid bacterium isolated from palm
      wine.
AB  - A novel lactic acid bacterium, strain TMW 2.694(T), was isolated among other
      lactic acid bacteria from palm wine, an alcoholic beverage produced from the sap
      of various palm tree species. Strain TMW 2.694(T) is a Gram-positive,
      facultatively anaerobic, catalase-negative, non-spore-forming coccus, occurring
      in long chains. Phylogenetic analysis based on 16S rRNA gene sequencing
      positioned strain TMW 2.694(T) in a distinct line of descent within the genus
      Leuconostoc, with the closest neighbours being Leuconostoc lactis JCM 6123(T)
      (98.7 % sequence similarity) and Leuconostoc citreum DSM 5577(T) (98.8 % sequence
      similarity). Comparative sequencing of the additional phylogenetic markers dnaK
      and recA confirmed the 16S rRNA gene tree topology. Genomic DNA-DNA similarities
      of strain TMW 2.694(T) to L. lactis DSM 20202(T) and L. citreum DSM 5577(T) were
      45.1 and 17.7 %, respectively. The DNA G+C content is 36.4 mol%. Thus, we propose
      a novel species within the genus Leuconostoc, with the name Leuconostoc palmae
      sp. nov. and the type strain TMW 2.694(T) (=DSM 21144(T) =LMG 24510(T)).

PMID- 19406773
TI  - Marinactinospora thermotolerans gen. nov., sp. nov., a marine actinomycete
      isolated from a sediment in the northern South China Sea.
AB  - A novel marine actinomycete, designated SCSIO 00652(T), was isolated from a
      marine sediment collected from the northern South China Sea at a depth of 3865 m.
      The strain formed branched substrate mycelia and no fragmentation was found.
      Abundant aerial mycelia differentiated into long spore chains and the spores had
      a wrinkled surface. Growth occurred on ISP medium 2 with 0-5 % (w/v) NaCl and at
      10-55 degrees C. The whole-cell hydrolysate contained meso-diaminopimelic acid
      and glucose as the whole-cell sugar. blast search results based on an almost
      complete 16S rRNA gene sequence showed the novel strain had the highest
      similarity (96.5 %) with Nocardiopsis trehalosi VKM Ac-942(T). The phylogenetic
      tree of the family Nocardiopsaceae indicated that strain SCSIO 00652(T) formed a
      distinct lineage at the deepest branch with a high bootstrap value. Additionally,
      the profiles of menaquinones, phospholipids and fatty acids showed there were
      marked differences between strain SCSIO 00652(T) and the recognized genera of the
      family Nocardiopsaceae. Based on the polyphasic data, a new genus,
      Marinactinospora gen. nov., is proposed within the family Nocardiopsaceae with
      the type species Marinactinospora thermotolerans sp. nov. The type strain of the
      type species is SCSIO 00652(T) (=DSM 45154(T)=CCTCC AA 208041(T)).

PMID- 19406774
TI  - Saccharibacillus kuerlensis sp. nov., isolated from a desert soil.
AB  - A taxonomic study was performed on strain HR1(T), which was isolated from a
      desert soil sample collected from Xinjiang Province (China). Cells were aerobic,
      Gram-positive-staining, pink-pigmented, sporulating rods with a single lateral
      flagellum. The organism can grow at 15-42 degrees C and pH 5.0-10.0, optimally at
      30-37 degrees C and pH 6.0-8.0. Growth is inhibited by 6 % NaCl. Analysis of
      almost-complete 16S rRNA gene sequence revealed that the isolate represents a
      distinct taxon within the genus Saccharibacillus; Saccharibacillus sacchari LMG
      24085(T) was the nearest relative (97.9 % sequence similarity). DNA-DNA
      hybridization showed 29.6 % genetic relatedness between strain HR1(T) and S.
      sacchari LMG 24085(T). The major isoprenoid quinone was MK-7 and the predominant
      fatty acid was anteiso-C(15 : 0) (50.3 %). The G+C content of the DNA was 50.5
      mol%. Therefore, based on phenotypic criteria and the phylogenetic position,
      strain HR1(T) belongs to a previously unidentified species of the genus
      Saccharibacillus, for which the name Saccharibacillus kuerlensis sp. nov. is
      proposed. The type strain is HR1(T) (=KCTC 13182(T) =JCM 14865(T) =CGMCC
      1.6964(T)).

PMID- 19406775
TI  - Lysobacter panaciterrae sp. nov., isolated from soil of a ginseng field.
AB  - A Gram-negative, aerobic, rod-shaped, non-spore-forming bacterial strain,
      designated Gsoil 068(T), was isolated from soil of a ginseng field in Pocheon
      Province (South Korea), and was characterized to determine its taxonomic position
      by using a polyphasic approach. Comparative 16S rRNA gene sequence analysis
      showed that strain Gsoil 068(T) belonged to the family Xanthomonadaceae, class
      Gammaproteobacteria, and was related most closely to Lysobacter brunescens ATCC
      29482(T) and Lysobacter gummosus ATCC 29489(T) (96.1 % sequence similarity). The
      G+C content of the genomic DNA of strain Gsoil 068(T) was 67.0 mol%. The
      detection of a quinone system with ubiquinone Q-8 as the predominant component
      and a fatty acid profile with iso-C(15 : 0), iso-C(17 : 1)omega9c, iso-C(17 : 0)
      and iso-C(11 : 0) 3-OH as the major components supported the affiliation of
      strain Gsoil 068(T) to the genus Lysobacter. On the basis of its phenotypic
      properties and phylogenetic distinctiveness, strain Gsoil 068(T) is considered to
      represent a novel species of the genus Lysobacter, for which the name Lysobacter
      panaciterrae sp. nov. is proposed. The type strain is Gsoil 068(T) (=KCTC
      12601(T) =DSM 17927(T)).

PMID- 19406776
TI  - Thermotalea metallivorans gen. nov., sp. nov., a thermophilic, anaerobic
      bacterium from the Great Artesian Basin of Australia aquifer.
AB  - A strictly anaerobic, thermophilic bacterium, designated strain B2-1(T), was
      isolated from microbial mats colonizing a runoff channel formed by free-flowing
      thermal water from a Great Artesian Basin, Australia, bore well (registered
      number 17263). The cells of strain B2-1(T) were slightly curved rods (3.0-3.5 x
      0.6-0.7 microm) which stained Gram-negative. The strain grew optimally in
      tryptone-yeast extract-glucose medium at 50 degrees C (temperature growth range
      30-55 degrees C) and a pH of 8 (pH growth range 6.5-9). Strain B2-1(T) grew
      poorly on yeast extract (0.2 %) and/or tryptone (0.2 %), which were obligately
      required for growth on other energy sources, including a range of other
      carbohydrates and organic acids, but not amino acids. The end-products of glucose
      fermentation were ethanol and acetate. In the presence of 0.2 % yeast extract,
      iron(III), manganese(IV) and elemental sulfur were reduced but sulfate,
      thiosulfate, sulfite, nitrate and nitrite were not reduced. Growth was inhibited
      by chloramphenicol, streptomycin, tetracycline, penicillin, ampicillin, sodium
      azide and by NaCl concentrations greater than 4 % (w/v). The DNA G+C content was
      48+/-1 mol% as determined by the thermal denaturation method. 16S rRNA gene
      sequence analysis indicated that strain B2-1(T) was a member of the family
      Clostridiaceae, class Clostridia, phylum Firmicutes and was most closely related
      to Geosporobacter subterraneus DSM 17957(T) (89.9 % similarity). On the basis of
      16S rRNA gene sequence comparisons and physiological characteristics, strain B2
      1(T) is considered to represent a novel species of a new genus, for which the
      name Thermotalea metallivorans gen. nov., sp. nov. is proposed. The type strain
      is B2-1(T) (=KCTC 5625(T)=JCM 15105(T)=DSM 21119(T)).

PMID- 19406778
TI  - Clostridium sufflavum sp. nov., isolated from a methanogenic reactor treating
      cattle waste.
AB  - A strictly anaerobic, mesophilic, cellulolytic bacterial strain, designated CDT
      1(T), was isolated from rice-straw residue from a methanogenic reactor treating
      waste from cattle farms. The isolation was performed using enrichment culture
      with filter paper as a substrate. Cells stained Gram-negative, but reacted Gram
      positively in the KOH test. Cells were slightly curved rods and were motile by
      means of peritrichous flagella. The strain produced yellow pigment when grown on
      filter-paper fragments. Although spore formation was not confirmed
      microscopically, thermotolerant cells were produced when the strain was grown on
      filter paper. The optimum temperature for growth was 33 degrees C and the optimum
      pH was 7.4. Oxidase, catalase and nitrate-reducing activities were absent. The
      strain utilized xylose, fructose, glucose, cellobiose, xylooligosaccharide,
      cellulose (filter-paper fragments and ball-milled filter paper) and xylan. The
      major fermentation products were acetate, ethanol, H(2) and CO(2). The major
      cellular fatty acids were iso-C(15 : 0), iso-C(14 : 0) and C(16 : 0) DMA. The
      cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic
      diamino acid. The genomic DNA G+C content was 40.7 mol%. On the basis of 16S rRNA
      gene sequence similarities, strain CDT-1(T) could be placed in cluster III of the
      genus Clostridium, being closely related to type strains of Clostridium hungatei
      (96.6 % sequence similarity), Clostridium termitidis (96.2 %) and Clostridium
      papyrosolvens (96.1 %). On the basis of the cellular, physiological and
      phylogenetic differences between CDT-1(T) and its close relatives, this strain
      represents a novel species of the genus Clostridium, for which the name
      Clostridium sufflavum sp. nov. is proposed. The type strain is CDT-1(T) (=JCM
      14807(T)=DSM 19573(T)).

PMID- 19406777
TI  - Pyramidobacter piscolens gen. nov., sp. nov., a member of the phylum
      'Synergistetes' isolated from the human oral cavity.
AB  - Four strains of anaerobic, Gram-negative bacilli isolated from the human oral
      cavity were subjected to a comprehensive range of phenotypic and genotypic tests
      and were found to comprise a homogeneous group distinct from any species with
      validly published names. 16S rRNA and 23S rRNA gene sequence analyses and DNA-DNA
      reassociation data revealed that the strains constituted a novel group within the
      phylum 'Synergistetes' and were most closely related to Jonquetella anthropi. Two
      libraries of randomly cloned DNA were prepared from strain W5455(T) and were
      sequenced to provide a genome survey as a resource for metagenomic studies. A new
      genus and novel species, Pyramidobacter piscolens gen. nov., sp. nov., is
      proposed to accommodate these strains. The genus Pyramidobacter comprises strains
      that are anaerobic, non-motile, asaccharolytic bacilli that produce acetic and
      isovaleric acids and minor to trace amounts of propionic, isobutyric, succinic
      and phenylacetic acids as end products of metabolism. P. piscolens gen. nov., sp.
      nov. produced hydrogen sulphide but was otherwise largely biochemically
      unreactive. Growth was stimulated by the addition of glycine to broth media. The
      G+C content of the DNA of the type strain was 59 mol%. The type strain of
      Pyramidobacter piscolens sp. nov. is W5455(T) (=DSM 21147(T)=CCUG 55836(T)).

PMID- 19406779
TI  - Treponema pedis sp. nov., a spirochaete isolated from bovine digital dermatitis
      lesions.
AB  - Bovine digital dermatitis (BDD) is a debilitating infection that is being
      increasingly recognized in livestock worldwide. Several treponeme phylotypes have
      been identified in BDD lesions, although only a single BDD-associated treponeme
      taxon (Treponema brennaborense) has been proposed thus far. In a previous study,
      we observed that four BDD-associated spirochaete isolates formed a distinct
      phylogenetic cluster on the basis of 16S rRNA gene sequence analysis and shared
      less than 97 % sequence similarity with recognized treponeme species. Further
      characterization of these isolates on the basis of growth characteristics, flaB2
      gene sequences, enzyme profiles and cell morphology confirmed that they formed a
      coherent taxonomic group displaying marked genotypic and phenotypic differences
      with respect to recognized treponeme species. The four novel isolates displayed a
      novel 3 : 6 : 3 flagellar pattern rather than the 2 : 4 : 2 pattern shown by
      their closest relatives and exhibited esterase C4, esterase lipase C8, trypsin
      and chymotrypsin enzyme activities. Therefore these four new isolates represent a
      novel species of the genus Treponema, for which the name Treponema pedis sp. nov.
      is proposed. The type strain is T3552B(T) (=DSM 18691(T)=NCTC 13403(T)).

PMID- 19406780
TI  - Planotetraspora thailandica sp. nov., isolated from soil in Thailand.
AB  - A Gram-positive-staining, filamentous bacterial strain that developed cylindrical
      sporangia containing four oval- to rod-shaped spores at the ends of short
      sporangiophores on branched aerial mycelium was isolated from tropical rainforest
      soil near a hot spring. The cell-wall peptidoglycan contained meso-diaminopimelic
      acid, glutamic acid and alanine as cell-wall amino acids; the whole-cell
      hydrolysate contained rhamnose, madurose, glucose, galactose and 3-O
      methylmannose as whole-cell sugars. The predominant menaquinone was MK-9(H(4)).
      Mycolic acids were not detected. The diagnostic phospholipid was
      phosphatidylethanolamine. The predominant cellular fatty acids were iso-C(16 : 0)
      and 10-methylated C(17 : 0). The G+C content of the DNA was 71.1 mol%. The
      phenotypic and chemotaxonomic analyses showed that the isolate had
      characteristics typical of members of the genus Planotetraspora. Furthermore, 16S
      rRNA gene sequence analysis also indicated that this strain belongs to the genus
      Planotetraspora, but as a putative novel species. Following phenotypic,
      chemotaxonomic and genotypic studies, the isolate is proposed to be a
      representative of a novel species, to be named Planotetraspora thailandica sp.
      nov. The type strain is BCC 21825(T) (=NBRC 104271(T)). An emended description of
      the genus Planotetraspora is also presented.

PMID- 19406781
TI  - Parvularcula lutaonensis sp. nov., a moderately thermotolerant marine bacterium
      isolated from a coastal hot spring.
AB  - Strain CC-MMS-1(T), a motile, Gram-negative, orange-pigmented bacterium, was
      isolated from water samples collected from a rare coastal hot spring at Lutao, an
      island off the eastern coast of Taiwan. 16S rRNA gene sequence studies showed
      that the novel strain was closely related to Parvularcula bermudensis HTCC2503(T)
      (95.1 % sequence similarity). The fatty acid profile was slightly different from
      P. bermudensis HTCC2503(T). The results of physiological and biochemical tests
      allowed clear phenotypic differentiation of the novel isolate from P. bermudensis
      HTCC2503(T). It is evident from the genotypic and phenotypic data that the strain
      should be classified as a novel species in the genus Parvularcula. The name
      proposed for this taxon is Parvularcula lutaonensis sp. nov. The type strain is
      CC-MMS-1(T) (=BCRC 17814(T)=KCTC 22245(T)).

PMID- 19406782
TI  - Paenibacillus pueri sp. nov., isolated from Pu'er tea.
AB  - Pu'er tea is a fermented drink made from the leaves of the tea plant, Camellia
      sinensis. Two novel bacteria, designated strains b09i-3(T) and b13i-1, were
      isolated during the process of fermentation of this tea. These isolates were Gram
      positive, endospore-forming, motile rods that grew at 25-42 degrees C and pH 5.5
      10.4. The DNA G+C content was 56.6-58.4 mol%, the predominant isoprenoid quinone
      was MK-7 and the predominant cellular fatty acid was anteiso-C(15 : 0) (49.0-50 %
      of the total). Phylogenetic analysis based on 16S rRNA gene sequences showed that
      strains b09i-3(T) and b13i-1 shared 99.9 % similarity and were affiliated with a
      cluster within the family Paenibacillaceae. Strains b09i-3(T) and b13i-1 were
      related most closely to Paenibacillus ginsengihumi DCY16(T) (97 % 16S rRNA gene
      sequence similarity). Levels of DNA-DNA relatedness between the two novel
      isolates and P. ginsengihumi DCY16(T) were below 56 %. The phylogenetic and
      phenotypic characteristics of these novel isolates allowed them to be
      distinguished clearly from recognized species of the genus Paenibacillus. Based
      on these data, strains b09i-3(T) and b13i-1 are considered to represent a novel
      species of the genus Paenibacillus, for which the name Paenibacillus pueri sp.
      nov. is proposed. The type species is b09i-3(T) (=KCTC 13223(T)=CECT 7360(T)).

PMID- 19406783
TI  - Pediococcus lolii sp. nov., isolated from ryegrass silage.
AB  - A Gram-positive, coccus-shaped, lactic acid bacterium, strain NGRI 0510Q(T), was
      isolated from ryegrass silage produced in Okinawa Prefecture, Japan. The cell is
      non-spore-forming, non-motile, and occurs in pairs or tetrads. The strain is
      homofermentative and produces d- and l-lactic acid from glucose. Phylogenetic
      analysis based on 16S rRNA gene sequences revealed that strain NGRI 0510Q(T)
      belongs to the genus Pediococcus and clusters within the Pediococcus acidilactici
      and Pediococcus pentosaceus group, with 98.2 and 96.9 % sequence identity,
      respectively. DNA-DNA relatedness between strain NGRI 0510Q(T) and P.
      acidilactici JCM 8797(T) and P. pentosaceus JCM 5890(T) was 19.3 and 17.3 %,
      respectively. Based on its phenotypic characteristics, phylogenetic relationship
      and DNA-DNA relatedness, NGRI 0510Q(T) (=JCM 15055(T)=DSM 19927(T)) represents
      the type strain of a novel species, for which the name Pediococcus lolii sp. nov.
      is proposed.

PMID- 19406784
TI  - Gordonia cholesterolivorans sp. nov., a cholesterol-degrading actinomycete
      isolated from sewage sludge.
AB  - The taxonomic position of the cholesterol-degrading strain Chol-3(T), isolated
      from a sewage sludge sample, was clarified using a polyphasic taxonomic approach.
      Phylogenetic analysis of its 16S rRNA gene sequence, whole-cell fatty acid
      profile and mycolic acid composition revealed that this isolate is a member of
      the genus Gordonia with the species Gordonia sihwensis, G. hydrophobica and G.
      shandongensis being the nearest phylogenetic neighbours. The results of DNA-DNA
      hybridization against its phylogenetically closest neighbours as well as the
      results of physiological and biochemical tests allowed genotypic and phenotypic
      differentiation of strain Chol-3(T) from the other Gordonia species with validly
      published names. Strain Chol-3(T) therefore merits recognition as a member of a
      novel species within the genus Gordonia, for which the name Gordonia
      cholesterolivorans sp. nov. is proposed. The type strain is Chol-3(T) (=CECT
      7408(T) =DSM 45229(T)).

PMID- 19406785
TI  - Microbacterium binotii sp. nov., isolated from human blood.
AB  - Two strains of non-spore-forming, rod-shaped, Gram-positive bacteria, CIP
      101303(T) and CIP 102116, were isolated from human blood in 1976 and 1977,
      respectively. These strains had chemotaxonomic markers that were consistent with
      classification in the genus Microbacterium, i.e. MK-10, MK-11 and MK-12 as the
      major menaquinones, predominant iso- and anteiso-branched cellular fatty acids,
      galactose, mannose and rhamnose as the cell-wall sugars and ornithine as the
      diamino acid in the cell-wall peptidoglycan. The DNA G+C content was 70-72 mol%.
      Comparative 16S rRNA gene sequence studies revealed that strains CIP 101303(T)
      and CIP 102116 belonged to the genus Microbacterium and that they were related
      closely to Microbacterium halotolerans. The level of DNA-DNA relatedness showed
      that the two isolates represented a separate genomic species. Based on phenotypic
      and genotypic results, it is proposed that strains CIP 101303(T) and CIP 102116
      be assigned to a novel species, Microbacterium binotii sp. nov. The type strain
      is CIP 101303(T) (=DSM 19164(T)).

PMID- 19406787
TI  - Description of 'Synergistetes' phyl. nov. and emended description of the phylum
      'Deferribacteres' and of the family Syntrophomonadaceae, phylum 'Firmicutes'.
AB  - The number of bacterial phyla has greatly increased in the past decade. Among
      them, a candidate division named 'Synergistes' was proposed in a phylogenetic
      study on the global diversity of bacteria. We previously described the genus
      Jonquetella and suggested that it belonged to this not yet well-delineated
      candidate phylum. 16S rRNA gene based-phylogeny studies were conducted using four
      reconstruction methods and 599 sequences forming five datasets were used in an
      alternative treeing approach. These analyses indicated that the genera
      Aminiphilus, Aminobacterium, Aminomonas, Anaerobaculum, Dethiosulfovibrio,
      Jonquetella, Synergistes, Thermanaerovibrio and Thermovirga should be grouped in
      the same high-level taxon. This taxon was shown to be a phylum-rank lineage in
      the domain Bacteria and, because of the prior use of the name Synergistes for a
      genus, the name 'Synergistetes' is proposed for this candidate phylum. We also
      propose an emended delineation of the phylum 'Deferribacteres', which is now only
      represented by the family Deferribacteriaceae. The emended family
      Syntrophomonadaceae is limited to the genera Pelospora, Syntrophomonas,
      Syntrophothermus and Thermosyntropha.

PMID- 19406786
TI  - Glycomyces scopariae sp. nov. and Glycomyces mayteni sp. nov., isolated from
      medicinal plants in China.
AB  - Two actinomycete strains, designated YIM 56256(T) and YIM 61331(T), were isolated
      from the roots of Scoparia dulcis and Maytenus austroyunnanensis, two Chinese
      medicinal plants, and their taxonomic status was established based on a
      polyphasic investigation. The organisms were found to have chemical and
      morphological markers typical of members of the genus Glycomyces. 16S rRNA gene
      sequence analysis showed that they were closely related to each other and to
      Glycomyces sambucus E71(T). A battery of physiological characteristics and levels
      of DNA-DNA relatedness indicated that strains YIM 56256(T) and YIM 61331(T)
      represent two novel species, clearly different from the related known Glycomyces
      species. On the basis of the data presented, it is evident that each of these
      strains represents a novel species of the genus Glycomyces, for which the names
      Glycomyces scopariae sp. nov. (type strain YIM 56256(T) =KCTC 19158(T) =DSM
      44968(T)) and Glycomyces mayteni sp. nov. (type strain YIM 61331(T) =KCTC
      19527(T) =CCTCC AA 208004(T)) are proposed.

PMID- 19406788
TI  - Nitratireductor kimnyeongensis sp. nov., isolated from seaweed.
AB  - An aerobic, Gram-negative, catalase-positive, oxidase-positive bacterium was
      isolated from a dried seaweed sample collected from Kimnyeong Beach in Jeju,
      Republic of Korea. The cells of the organism, designated strain KY 101(T), were
      rods (0.4-0.5x1.2-2.7 mum) and motile by means of flagella. The colonies of the
      cells were 0.5-1 mm in diameter, smooth, circular, convex and light yellow in
      colour. The isolate showed growth at 10-40 degrees C, pH 6.1-12.1 and in the
      presence of 7 % NaCl. The major fatty acid was summed feature C(18 :
      1)omega7c/C(18 : 1)omega9c/C(18 : 1)omega12t and the DNA G+C content was 60.4
      mol%. 16S rRNA gene sequence studies showed that the organism was
      phylogenetically related to the family Phyllobacteriaceae, with Nitratireductor
      aquibiodomus (99.1 % sequence similarity) as the closest neighbour. The level of
      DNA-DNA relatedness between strain KY 101(T) and N. aquibiodomus DSM 15645(T) was
      18.4-23.2 % (duplicate measurements). The combination of phenotypic differences
      and DNA-DNA hybridization data supports the suggestion that the isolate
      represents a novel species of the genus Nitratireductor, for which the name
      Nitratireductor kimnyeongensis sp. nov. is proposed. The type strain is strain KY
      101(T) (=KACC 11904(T)=JCM 14851(T)).

PMID- 19406789
TI  - Caldimicrobium rimae gen. nov., sp. nov., an extremely thermophilic,
      facultatively lithoautotrophic, anaerobic bacterium from the Uzon Caldera,
      Kamchatka.
AB  - An extremely thermophilic, strictly anaerobic, facultatively
      chemolithoautotrophic bacterium designated strain DS(T) was isolated from
      Treshchinnyi Spring, one of the hottest springs of the Uzon Caldera (Kamchatka,
      Russia). Cells of the novel organism were Gram-negative rods, about 1.0-1.2
      microm long and 0.5 microm wide. The temperature range for growth was 52-82
      degrees C, with an optimum at 75 degrees C. Growth was observed at pH 6.8-7.4,
      and the optimum pH was 7.0-7.2. Strain DS(T) was able to grow
      lithoautotrophically with hydrogen in the presence of CO(2) as a carbon source
      and thiosulfate or elemental sulfur as an electron acceptor. It also grew well
      with ethanol, fumarate, succinate or malate in the presence of thiosulfate. Yeast
      extract was not required for growth and did not stimulate growth. The genomic DNA
      G+C content was 35.2 mol%. Phylogenetic analysis of the 16S rRNA gene sequence
      indicated that the novel organism was a member of the family
      Thermodesulfobacteriaceae. On the basis of phylogenetic and physiological
      considerations, it is proposed that strain DS(T) represents a new genus and
      species, Caldimicrobium rimae gen. nov., sp. nov. The type strain of
      Caldimicrobium rimae is DS(T) (=DSM 19393(T) =VKM B-2460(T)).

PMID- 19406790
TI  - Aquitalea denitrificans sp. nov., isolated from a Korean wetland.
AB  - A novel bacterium, designated strain 5YN1-3(T), was isolated from wetland peat
      collected from Yongneup, Korea. The bacterium was facultatively anaerobic, Gram
      negative, yellow-coloured, rod-shaped, mesophilic and motile with one polar
      flagellum. The strain grew optimally at 30 degrees C, at pH 6.0-9.0 and with 0-1
      % NaCl (w/v). 16S rRNA gene sequence analysis showed the highest similarity to
      the sequence from Aquitalea magnusonii TRO-001DR8(T), with 98.7 % sequence
      similarity. However, strain 5YN1-3(T) showed DNA-DNA relatedness of 43 % (40 % in
      a reciprocal experiment) with A. magnusonii LMG 23054(T). The strain contained
      summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c) and C(16 : 0) as
      major cellular fatty acids. On the basis of DNA-DNA relatedness and physiological
      and biochemical characterization, strain 5YN1-3(T) should be assigned to a novel
      species of the genus Aquitalea, for which the name Aquitalea denitrificans sp.
      nov. is proposed. The type strain is 5YN1-3(T) (=KACC 12729(T) =DSM 21300(T)).

PMID- 19406791
TI  - Mycobacterium riyadhense sp. nov., a non-tuberculous species identified as
      Mycobacterium tuberculosis complex by a commercial line-probe assay.
AB  - A non-chromogenic, slowly growing Mycobacterium strain was isolated from a
      maxillary sinus lavage from a symptomatic patient in Riyadh, Saudi Arabia. It was
      initially identified as a member of the Mycobacterium tuberculosis complex by a
      commercial line-probe assay. Its 16S rRNA, hsp65 and rpoB gene and 16S-23S
      internal transcribed spacer sequences were unique; phylogenetic analysis based on
      the 16S rRNA gene sequence groups this organism close to Mycobacterium szulgai
      and Mycobacterium malmoense. Its unique biochemical properties and mycolic acid
      profile support separate species status. We propose the name Mycobacterium
      riyadhense sp. nov. to accommodate this strain. The type strain is
      NLA000201958(T) (=CIP 109808(T) =DSM 45176(T)).

PMID- 19406792
TI  - Re-examination of the taxonomic position of Bacillus silvestris Rheims et al.
      1999 and proposal to transfer it to Solibacillus gen. nov. as Solibacillus
      silvestris comb. nov.
AB  - Following the transfer of three of the six species enclosed in the original
      definition of rRNA group 2 of Bacillus to the genus Sporosarcina and two to
      Lysinibacillus, other species of this group, some of which were added later,
      still await taxonomic revision. In a recent publication, a set of 'core'
      characteristics was proposed for species to be included in the genus Bacillus
      (Kampfer et al., 2006). Except for Bacillus silvestris, however, several or none
      of these properties are available for members of rRNA group 2. According to our
      analysis of data including the 'core' characteristics, Bacillus silvestris should
      not be a member of the genus Bacillus. We therefore propose the establishment of
      a new genus, Solibacillus gen. nov., and transfer Bacillus silvestris to this
      genus as Solibacillus silvestris comb. nov., with the type strain HR3-23(T) (=DSM
      12223(T)=ATCC BAA-269(T)=CIP 106059(T)).

PMID- 19406793
TI  - Desulfovibrio tunisiensis sp. nov., a novel weakly halotolerant, sulfate-reducing
      bacterium isolated from exhaust water of a Tunisian oil refinery.
AB  - A novel weakly halotolerant, sulfate-reducing bacterium, designated strain
      RB22(T), was isolated from exhaust water of a Tunisian oil refinery. Cells of
      strain RB22(T) were Gram-negative, motile, vibrio-shaped or sigmoid and non-spore
      forming, and occurred singly or in chains. Strain RB22(T) grew between 15 and 45
      degrees C (optimum, 37 degrees C) and at pH 4.5 to 9 (optimum, pH 7). NaCl was
      not required for growth, but the strain tolerated high NaCl concentrations (up to
      70 g l(-1)) with an optimum of 40 g l(-1). Sulfate, thiosulfate, sulfite and
      elemental sulfur served as electron acceptors, but not fumarate. Nitrate and
      nitrite were not reduced. Strain RB22(T) utilized lactate, formate, fumarate,
      succinate, glycerol, H(2)+CO(2) and methanol as substrates. The DNA G+C content
      was found to be 59.6 mol%. Phylogenetic analysis based on the 16S rRNA gene
      revealed that the isolate was a member of the genus Desulfovibrio, with no close
      relatives at the species level (16S rRNA gene sequence similarity of less than 95
      %). Strain RB22(T) exhibited levels of 16S rRNA gene sequence similarity of 94.6
      and 94.12 % to the type strains of the closely related species Desulfovibrio
      aespoeensis and Desulfovibrio dechloracetivorans, respectively. On the basis of
      genotypic and phylogenetic characteristics, and significant phenotypic
      differences, we suggest that strain RB22(T) represents a novel species, for which
      the name Desulfovibrio tunisiensis sp. nov. is proposed. The type strain is
      RB22(T) (=NCIMB 14400(T)=JCM 15076(T)=DSM 19275(T)).

PMID- 19406795
TI  - Micrococcus endophyticus sp. nov., isolated from surface-sterilized Aquilaria
      sinensis roots.
AB  - A Gram-positive bacterial strain, designated YIM 56238(T), was isolated from
      plant roots (Aquilaria sinensis), and characterized by using a polyphasic
      approach. Strain YIM 56238(T) grew optimally at pH 7.0-8.0 and at 28 degrees C.
      Analysis of the 16S rRNA gene sequence of strain YIM 56238(T) indicated that it
      belongs to the genus Micrococcus. Chemotaxonomic data strongly supported the
      classification of this strain within the genus Micrococcus: the cell-wall
      peptidoglycan contained lysine, glutamic acid, alanine and glycine; the
      predominant menaquinones were MK-8(H(2)) (63.6 %) and MK-7(H(2)) (21.1 %); the
      phospholipids were diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylinositol and an unknown ninhydrin-negative phospholipid; and the
      major cellular fatty acids were iso-C(15 : 0) (30.95 %) and anteiso-C(15 : 0)
      (53.75 %). The G+C content of the genomic DNA was 72.9 mol%. A number of
      physiological features were found that clearly distinguished strain YIM 56238(T)
      from recognized species of the genus Micrococcus. DNA-DNA hybridization studies
      suggested that the novel strain represents a separate genomic species. On the
      basis of the data, therefore, strain YIM 56238(T) represents a novel species of
      the genus Micrococcus, for which the name Micrococcus endophyticus sp. nov. is
      proposed. The type strain is YIM 56238(T) (=DSM 17945(T)=KCTC 19156(T)).

PMID- 19406794
TI  - Methanolobus zinderi sp. nov., a methylotrophic methanogen isolated from a deep
      subsurface coal seam.
AB  - A methanogenic organism from the domain Archaea (SD1(T)) was isolated from saline
      water released from a coal seam located 926 m below the surface via a methane
      producing well near Monroe, Louisiana, USA. Growth and methanogenesis were
      supported with methanol, monomethylamine, dimethylamine or trimethylamine, but
      not with dimethylsulfide, formate, acetate or H(2)/CO(2). Cells grew in high-salt
      minimal medium but growth was stimulated with yeast extract or tryptone. Cells
      were single, non-motile, irregular coccoids 0.5-1.0 microm in diameter and the
      cell wall contained protein. Conditions for the maximum rate of growth were 40-50
      degrees C, 0.2-0.6 M NaCl, 100->or=200 mM MgCl(2), and pH 7.0-8.0. The G+C
      content of the genomic DNA was 42+/-1mol %. A comparison of 16S rRNA gene
      sequences indicated that strain SD1(T) was most closely related to Methanolobus
      oregonensis DSM 5435(T) with 96 % gene sequence similarity. It is proposed that
      strain SD1(T) represents a novel species, Methanolobus zinderi sp. nov. The type
      strain is SD1(T) (=ATCC BAA-1601(T)=DSM 21339(T)).

PMID- 19406796
TI  - Saccharopolyspora jiangxiensis sp. nov., isolated from grass-field soil.
AB  - An actinomycete isolated from soil from a field of grass was analysed using a
      polyphasic taxonomic approach. The organism, designated strain W12(T), was found
      to have a range of chemical and morphological properties consistent with its
      classification in the genus Saccharopolyspora. An almost-complete 16S rRNA gene
      sequence determined for the strain was aligned with corresponding sequences for
      representatives of the genus Saccharopolyspora, using two tree-making algorithms.
      The novel organism formed a monophyletic clade with the type strain of
      Saccharopolyspora antimicrobica, but the DNA-DNA relatedness value was low.
      Strain W12(T) also had a phenotypic profile that readily distinguished it from
      recognized representatives of the genus Saccharopolyspora. It is evident from the
      combined genotypic and phenotypic data that the new organism should be classified
      as a novel species of the genus Saccharopolyspora. The name proposed for this new
      taxon is Saccharopolyspora jiangxiensis sp. nov., with strain W12(T) (=CGMCC
      4.3529(T)=JCM 14613(T)) as the type strain.

PMID- 19406797
TI  - Ferrimicrobium acidiphilum gen. nov., sp. nov. and Ferrithrix thermotolerans gen.
      nov., sp. nov.: heterotrophic, iron-oxidizing, extremely acidophilic
      actinobacteria.
AB  - Two novel extremely acidophilic, iron-oxidizing actinobacteria were isolated, one
      from a mine site in North Wales, UK (isolate T23(T)), and the other from a
      geothermal site in Yellowstone National Park, Wyoming, USA (Y005(T)). These new
      actinobacteria belong to the subclass Acidimicrobidae, and in contrast to the
      only other classified member of the subclass (Acidimicrobium ferrooxidans), both
      isolates were obligate heterotrophs. The mine site isolate was mesophilic and
      grew as small rods, while the Yellowstone isolate was a moderate thermophile and
      grew as long filaments, forming macroscopic flocs in liquid media. Both isolates
      accelerated the oxidative dissolution of pyrite in yeast extract-amended
      cultures, but neither was able to oxidize reduced forms of sulfur. Ferrous iron
      oxidation enhanced growth yields of the novel mesophilic actinobacterium T23(T),
      though this was not confirmed for the Yellowstone isolate. Both isolates
      catalysed the dissimilatory reduction of ferric iron, using glycerol as electron
      donor, in oxygen-free medium. Based on comparative analyses of base compositions
      of their chromosomal DNA and of their 16S rRNA gene sequences, the isolates are
      both distinct from each other and from Acidimicrobium ferrooxidans, and are
      representatives of two novel genera. The names Ferrimicrobium acidiphilum gen.
      nov., sp. nov. and Ferrithrix thermotolerans gen. nov., sp. nov. are proposed for
      the mesophilic and moderately thermophilic isolates, respectively, with the
      respective type strains T23(T) (=DSM 19497(T)=ATCC BAA-1647(T)) and Y005(T) (=DSM
      19514(T)=ATCC BAA-1645(T)).

PMID- 19406798
TI  - Kineococcus xinjiangensis sp. nov., isolated from desert sand.
AB  - A brown-orange-pigmented, non-spore-forming, coccus-shaped actinomycete,
      designated S2-20(T), was isolated from desert sand from Xinjiang Province in
      China. The isolate stains Gram-positive, is motile and produces a brownish
      diffusible pigment. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that strain S2-20(T) was phylogenetically affiliated to the genus
      Kineococcus, and the sequence similarity to the type strains of Kineococcus
      species was less than 96 %, making it clear that strain S2-20(T) represents a
      species that is separate from recognized Kineococcus species. Its major fatty
      acid was anteiso-C(15 : 0). The major menaquinone was MK-9(H(2)). Whole-cell
      hydrolysates of strain S2-20(T) contained meso-diaminopimelic acid, arabinose and
      galactose. The DNA G+C content was 77.8 mol%. On the basis of phylogenetic,
      phenotypic and chemotaxonomic characteristics, strain S2-20(T) should be
      classified within a novel species of the genus Kineococcus, for which the name
      Kineococcus xinjiangensis sp. nov. is proposed. The type strain is S2-20(T)
      (=CCTCC AB 207179(T) =KCTC 19474(T)).

PMID- 19406799
TI  - Description of Rummeliibacillus stabekisii gen. nov., sp. nov. and
      reclassification of Bacillus pycnus Nakamura et al. 2002 as Rummeliibacillus
      pycnus comb. nov.
AB  - Strains of aerobic, Gram-positive, rod-shaped, round-spore-forming bacteria were
      isolated from different geographical locations and a subsequent polyphasic study
      was undertaken to clarify the taxonomic position of the round-spore-forming
      isolates strain KSC-SF6g(T), strain M32 and strain NBRC 12622. 16S rRNA gene
      sequence similarities demonstrated that these strains were most closely
      affiliated with Bacillus pycnus NRRL NRS-1691(T) (98 %), with species of Kurthia
      (96 %) and Viridibacillus (94-96 %) as the next nearest relatives. However, while
      DNA-DNA hybridization studies showed approx. 70 % reassociation among strains KSC
      SF6g(T), M32 and NBRC 12622, DNA-DNA hybridization values between these strains
      and B. pycnus NRRL NRS-1691(T) never exceeded 13 %. Differences in the molecular
      structure of the cell-wall peptidoglycan could not differentiate these strains
      sufficiently from other closely related genera (Viridibacillus and Kurthia).
      However, Lys-Asp was present in strains KSC-SF6g(T), M32 and NBRC 12622, whereas
      l-Lys-d-Glu was reported in B. pycnus NRRL NRS-1691(T). The menaquinone MK-7 was
      dominant in strains KSC-SF6g(T), M32 and NBRC 12622 and members of the genus
      Kurthia, whereas MK-8 was abundant in Viridibacillus species. Strains KSC
      SF6g(T), M32 and NBRC 12622 exhibited fatty acid profiles consisting of major
      amounts of anteiso-C(15 : 0) ( approximately 50 %) and iso-C(15 : 0) (
      approximately 25 %) and moderate amounts of anteiso-C(17 : 0) ( approximately 7
      %), which discriminated them from closely related B. pycnus NRRL NRS-1691(T) and
      species of Viridibacillus (iso-C(15 : 0); 46-74 %). The authors propose that
      strains KSC-SF6g(T), M32 and NBRC 12622 and B. pycnus NRRL NRS-1691(T) be
      reclassified into a separate genus based on clear-cut differences in
      discriminative taxonomic markers and the distant placement of B. pycnus and the
      novel strains described herein from other species of this clade according to
      current 16S rRNA gene sequence-based relatedness ( approximately 4 % difference
      in sequence). We propose the placement of these isolates into the novel genus
      Rummeliibacillus gen. nov. For the new taxon comprising strains KSC-SF6g(T), M32
      and NBRC 12622, we propose the name Rummeliibacillus stabekisii gen. nov., sp.
      nov. (the type species of Rummeliibacillus), represented by the type strain KSC
      SF6g(T) (=NRRL B-51320(T) =NBRC 104870(T)). In addition, Bacillus pycnus, which
      bears traits distinct from other round-spore-forming species [i.e. absence of
      growth at high NaCl (7 %), positive reaction for gelatin liquefaction], is
      reclassified as Rummeliibacillus pycnus comb. nov. (type strain JCM 11075(T)
      =NRRL NRS-1691(T)) based on phylogenetic affiliations and phenotypic
      characterization.

PMID- 19406800
TI  - Fervidicola ferrireducens gen. nov., sp. nov., a thermophilic anaerobic bacterium
      from geothermal waters of the Great Artesian Basin, Australia.
AB  - A strictly anaerobic, thermophilic bacterium, designated strain Y170(T), was
      isolated from a microbial mat colonizing thermal waters of a run-off channel
      created by the free-flowing waters of a Great Artesian Basin (GAB) bore well (New
      Lorne bore; registered number 17263). Cells of strain Y170(T) were slightly
      curved rods (1.2-12x0.8-1.1 mum) and stained Gram-negative. The strain grew
      optimally in tryptone-yeast extract-glucose medium at 70 degrees C (temperature
      range for growth was 55-80 degrees C) and pH 7 (pH range for growth was 5-9).
      Strain Y170(T) grew poorly on yeast extract as a sole carbon source, but not on
      tryptone (0.2 %). Yeast extract could not be replaced by tryptone and was
      obligately required for growth on tryptone, peptone, glucose, fructose,
      galactose, cellobiose, mannose, sucrose, xylose, mannitol, formate, pyruvate,
      Casamino acids and threonine. No growth was observed on arabinose, lactose,
      maltose, raffinose, chitin, xylan, pectin, starch, acetate, benzoate, lactate,
      propionate, succinate, myo-inositol, ethanol, glycerol, amyl media, aspartate,
      leucine, glutamate, alanine, arginine, serine and glycine. End products detected
      from glucose fermentation were acetate, ethanol and presumably CO(2) and H(2).
      Iron(III), manganese(IV), thiosulfate and elemental sulfur, but not sulfate,
      sulfite, nitrate or nitrite, were used as electron acceptors in the presence of
      0.2 % yeast extract. Iron(III) in the form of amorphous Fe(III) oxhydroxide and
      Fe(III) citrate was also reduced in the presence of tryptone, peptone and
      Casamino acids, but not with chitin, xylan, pectin, formate, starch, pyruvate,
      acetate, benzoate, threonine, lactate, propionate, succinate, inositol, ethanol,
      glycerol, mannitol, aspartate, leucine, glutamate, alanine, arginine, serine or
      glycine. Strain Y170(T) was not able to utilize molecular hydrogen and/or carbon
      dioxide in the presence or absence of iron(III). Chloramphenicol, streptomycin,
      tetracycline, penicillin and ampicillin and NaCl concentrations greater than 2 %
      inhibited growth. The G+C content of the DNA was 48+/-1 mol% [sd (n=3); T(m)].
      16S rRNA gene sequence analysis indicated that strain Y170(T) is a member of the
      family Syntrophomonadaceae, class Clostridia, phylum Firmicutes and was most
      closely related to members of the genus Thermosediminibacter (mean similarity of
      93.6 %). On the basis of the 16S rRNA gene sequence comparisons and physiological
      characteristics, strain Y170(T) is considered to represent a novel species of a
      new genus, for which the name Fervidicola ferrireducens gen. nov., sp. nov. is
      proposed. The type strain is Y170(T) (=KCTC 5610(T)=JCM 15106(T)=DSM 21121(T)).

PMID- 19406801
TI  - Providencia sneebia sp. nov. and Providencia burhodogranariea sp. nov., isolated
      from wild Drosophila melanogaster.
AB  - Multiple isolates of the genus Providencia were obtained from the haemolymph of
      wild-caught Drosophila melanogaster fruit flies. Sixteen isolates were
      distinguished from the six previously described species based on 16S rRNA gene
      sequences. These isolates belonged to two distinct groups, which we propose each
      comprise previously undescribed species. Two isolates, designated A(T) and B(T),
      were characterized by DNA sequences of the fusA, lepA, leuS, gyrB and ileS
      housekeeping genes, whole-genome DNA-DNA hybridizations with their nearest
      relatives and utilization of substrates for metabolism. The closest phylogenetic
      relatives of strain A(T) are strain B(T) (86.9 % identity for the housekeeping
      genes) and Providencia stuartii DSM 4539(T) (86.0 % identity). The closest
      phylogenetic relatives of strain B(T) are strain A(T) (86.9 % identity) and P.
      stuartii DSM 4539(T) (86.6 % identity). The type strains of described species in
      this genus shared between 84.1 and 90.1 % identity for these sequences. DNA-DNA
      hybridization between the strain pairs A(T)-B(T), A(T)-P. stuartii DSM 4539(T)
      and B(T)-P. stuartii DSM 4539(T) all resulted in less than 25 % relatedness. In
      addition, patterns of utilization of amygdalin, arbutin, aesculin, salicin, d
      sorbitol, trehalose, inositol, d-adonitol and d-galactose distinguish strains
      A(T) and B(T) from other members of this genus. Strains A(T) and B(T) therefore
      represent novel species, for which the names Providencia sneebia sp. nov. (type
      strain A(T) =DSM 19967(T) =ATCC BAA-1589(T)) and Providencia burhodogranariea sp.
      nov. (type strain B(T) =DSM 19968(T) =ATCC BAA-1590(T)) are proposed.

PMID- 19406802
TI  - Corynebacterium lubricantis sp. nov., isolated from a coolant lubricant.
AB  - Three Gram-positive, rod-shaped, oxidase-negative, non-spore-forming, non-motile
      bacteria (KSS-3Se(T), KSS-4Se and KSS-10Se) were isolated from a coolant
      lubricant. 16S rRNA gene sequence analyses revealed almost identical sequences,
      with only a few (<10 positions) differences for these three isolates. Comparisons
      showed the highest similarities to Corynebacterium pilosum NCTC 11862(T) (97.6 %
      similarity with strain KSS-3Se(T)). Similarities with other established
      Corynebacterium species were lower than 97.0 %. Chemotaxonomic data studied for
      strain KSS-3Se(T) [polar lipids - major compounds phosphatidylglycerol and an
      unknown glycolipid, moderate amounts of phosphatidylinositol and
      diphosphatidylglycerol; polyamines (small amounts) - major compounds spermidine
      and spermine; quinones - significant amounts of menaquinones MK-9(H(2)), MK
      8(H(2)) and MK-7(H(2)); and major fatty acids - tuberculostearic acid (10-methyl
      C(18 : 0)), C(16 : 0) and C(18 : 1)omega9c] were congruent with those reported
      for Corynebacterium. The strain showed differences in phenotype from C. pilosum.
      DNA-DNA hybridizations between KSS-3Se(T) and C. pilosum DSM 20521(T) yielded a
      relatedness of 22.9 % (20.4 % in the reciprocal assay). From these results, it is
      evident that the organisms represent a novel species, for which the name
      Corynebacterium lubricantis sp. nov. is proposed (type strain KSS-3Se(T) =DSM
      45231(T) =CCUG 56567(T) =CCM 7546(T)).

PMID- 19406803
TI  - Roseovarius pacificus sp. nov., isolated from deep-sea sediment.
AB  - An aerobic, Gram-negative, ovoid to rod-shaped bacterial isolate, strain 81-2(T),
      was isolated from deep-sea sediment of the Western Pacific Ocean. Strain 81-2(T)
      was motile, formed faint pink colonies, and was catalase-positive, weakly
      positive for oxidase and required NaCl for growth. It did not synthesize
      bacteriochlorophyll a and its DNA G+C content was 62.3 mol%. The 16S rRNA gene
      sequence of strain 81-2(T) indicated that it was a member of the Roseobacter
      clade of the class Alphaproteobacteria, with moderate bootstrap support for
      inclusion in the genus Roseovarius. Its closest phylogenetic neighbour was the
      type strain of Roseovarius nubinhibens, which shared 95.8 % 16S rRNA gene
      sequence similarity; strain 81-2(T) was <95.0 % similar to strains of other
      related species and genera. Phenotypic, chemotaxonomic and phylogenetic data
      support assignment of this strain to the genus Roseovarius as a representative of
      a novel species. The name Roseovarius pacificus sp. nov. is proposed, with strain
      81-2(T) (=MCCC 1A00293(T)=CGMCC 1.7083(T)=LMG 24575(T)) as the type strain.

PMID- 19406804
TI  - Mucilaginibacter daejeonensis sp. nov., isolated from dried rice straw.
AB  - A novel strain, designated Jip 10(T), isolated from dried rice straw, was
      characterized by a polyphasic approach to clarify its taxonomic position. The
      isolate was Gram-negative, facultatively aerobic, heterotrophic, non-motile, non
      spore-forming and rod-shaped. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that the isolate clustered with the genus Mucilaginibacter in
      the phylum Bacteroidetes. 16S rRNA gene sequence similarities between strain Jip
      10(T) and the type strains of Mucilaginibacter gracilis and Mucilaginibacter
      paludis were 93.7 and 93.6 %, respectively. The G+C content of the genomic DNA
      was 48.1 mol%. Chemotaxonomic data [major menaquinone MK-7 and major fatty acids
      iso-C(15 : 0), iso-C(17 : 0) 3-OH and summed feature 3 (iso-C(15 : 0) 2-OH and/or
      C(16 : 1)omega7c)] supported the affiliation of strain Jip 10(T) to the genus
      Mucilaginibacter. However, the results of physiological and biochemical tests
      allowed phenotypic differentiation of strain Jip 10(T) from other
      Mucilaginibacter species with validly published names. Therefore, strain Jip
      10(T) (=KCTC 12639(T) =LMG 23488(T)) was classified in the genus Mucilaginibacter
      as the type strain of a novel species, for which the name Mucilaginibacter
      daejeonensis sp. nov. is proposed.

PMID- 19406805
TI  - Novel Campylobacter lari-like bacteria from humans and molluscs: description of
      Campylobacter peloridis sp. nov., Campylobacter lari subsp. concheus subsp. nov.
      and Campylobacter lari subsp. lari subsp. nov.
AB  - A polyphasic study was undertaken to clarify the taxonomic position of
      Campylobacter lari-like strains isolated from shellfish and humans. The diversity
      within the strain collection was initially screened by means of fluorescent
      amplified fragment length polymorphism analysis and whole-cell protein
      electrophoresis, revealing the existence of two clusters distinct from C. lari
      and other Campylobacter species. The divergence of these clusters was confirmed
      by phenotypic analysis and by 16S rRNA and hsp60 gene sequence analysis.
      Phylogenetic analysis identified C. lari, Campylobacter jejuni, Campylobacter
      coli and Campylobacter insulaenigrae as the closest phylogenetic neighbours of
      both taxa. DNA-DNA hybridizations revealed that one cluster, comprising 10
      strains, represented a novel Campylobacter species, for which the name
      Campylobacter peloridis sp. nov. is proposed, with 2314BVA(T) (=LMG 23910(T)
      =CCUG 55787(T)) as the type strain. The second cluster, comprising six strains,
      represents a novel subspecies within the species C. lari, for which the name
      Campylobacter lari subsp. concheus subsp. nov. is proposed, with 2897R(T) (=LMG
      21009(T) =CCUG 55786(T)) as the type strain. The description of C. lari subsp.
      concheus has the effect of automatically creating the subspecies Campylobacter
      lari subsp. lari subsp. nov. (type strain LMG 8846(T)=NCTC 11352(T)).

PMID- 19406806
TI  - Rhodobacter aestuarii sp. nov., a phototrophic alphaproteobacterium isolated from
      an estuarine environment.
AB  - An ovoid to rod-shaped, phototrophic, purple non-sulfur bacterium was isolated
      from a brown-coloured microbial mat from the brackish water of Bhitarkanika
      mangrove forest, Dangmal, Orissa, India. Cells of strain JA296(T) were Gram
      negative and motile, forming chains of four to eight cells. The colour of the
      cell suspension grown under anaerobic conditions in the light was yellowish
      green. Bacteriochlorophyll a and the carotenoids spheroidene and spheroidenone of
      the spirilloxanthin series were present as photosynthetic pigments. The bacterium
      was a facultative anaerobe and was able to grow photo-organoheterotrophically and
      chemo-organoheterotrophically. Thiamine was required as a growth factor. C(18 :
      1)omega7c was the dominant fatty acid. Internal cytoplasmic membranes were of the
      vesicular type. Strain JA296(T) did not require NaCl for growth. Phylogenetic
      analysis on the basis of 16S rRNA gene sequences showed that strain JA296(T) was
      most closely related to Rhodobacter capsulatus ATCC 11166(T) (95.5 % sequence
      similarity) and clustered with species of the genus Rhodobacter of the family
      Rhodobacteraceae, class Alphaproteobacteria. On the basis of 16S rRNA gene
      sequence analysis and morphological and physiological characteristics, strain
      JA296(T) represents a novel species of the genus Rhodobacter, for which the name
      Rhodobacter aestuarii sp. nov. is proposed; the type strain is JA296(T) (=JCM
      14887(T) =CCUG 55130(T)).

PMID- 19406807
TI  - Filimonas lacunae gen. nov., sp. nov., a member of the phylum Bacteroidetes
      isolated from fresh water.
AB  - A Gram-negative, strictly aerobic, motile, filamentous and viscous exopolymer
      producing bacterium, designated strain YT21(T), was isolated from fresh water.
      Phylogenetic analysis of the 16S rRNA gene sequence indicated that strain YT21(T)
      lies within a cluster containing the established genera Segetibacter, Terrimonas,
      Niastella and Chitinophaga in the phylum Bacteroidetes. However, the isolate
      represented a lineage distinct from these genera, with sequence similarities
      ranging from 88.9 to 91.8 %. The genomic G+C content was 45.2 mol%. The
      predominant isoprenoid quinone was MK-7. The major fatty acids were 15 : 0 iso,
      17 : 0 iso 3-OH and 15 : 1 iso G. On the basis of morphological features and
      phenotypic and phylogenetic data, strain YT21(T) represents a novel genus and
      species, for which the name Filimonas lacunae gen. nov., sp. nov. is proposed.
      The type strain of Filimonas lacunae is strain YT21(T) (=NBRC 104114(T) =DSM
      21054(T)).

PMID- 19406808
TI  - Donghicola xiamenensis sp. nov., a marine bacterium isolated from seawater of the
      Taiwan Strait in China.
AB  - A Gram-negative, ovoid rod-shaped bacterium that lacked bacteriochlorophyll a,
      designated strain Y-2(T), was isolated from seawater of the Taiwan Strait, China.
      The strain was oxidase- and catalase-positive, and reduced nitrate to nitrite.
      Optimal growth occurred at around pH 7.0 and 25 degrees C in the presence of 1-3
      % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that
      strain Y-2(T) belonged to the class Alphaproteobacteria and formed a coherent
      cluster with Donghicola eburneus SW-277(T) (96.2 % sequence similarity). The
      major whole-cell fatty acid was C(18 : 1)omega7c (75.42 %). Other characteristic
      fatty acids were C(18 : 0) (9.16 %) and C(16 : 0) (7.32 %). The DNA G+C content
      of strain Y-2(T) was 62.4 mol%. Therefore, based on phenotypic properties,
      phylogeny and genomic data, strain Y-2(T) should be placed in the genus
      Donghicola as representing a novel species, for which the name Donghicola
      xiamenensis sp. nov. is proposed. The type strain is Y-2(T) (=MCCC 1A00107(T)=LMG
      24574(T)=CGMCC 1.7081(T)).

PMID- 19406809
TI  - Saccharopolyspora rosea sp. nov., isolated from a patient with bronchial
      carcinoma.
AB  - The taxonomic status of a bacterium isolated from a patient with bronchial
      carcinoma was established using a polyphasic taxonomic approach. The strain had
      morphological and chemotaxonomic characteristics consistent with those of members
      of the genus Saccharopolyspora. The generic assignment was confirmed by
      comparative analysis of the 16S rRNA gene sequence, which showed that the strain
      constituted a distinct phyletic line, displaying 93.5-96.9 % sequence similarity
      with respect to members of the genus Saccharopolyspora. The isolate was
      distinguished from the type strains of recognized members of the genus
      Saccharopolyspora by means of various biochemical tests. The genotypic and
      phenotypic data obtained demonstrated that strain IMMIB L-1070(T) represents a
      novel species of the genus Saccharopolyspora, for which the name
      Saccharopolyspora rosea sp. nov. is proposed. The type strain is IMMIB L-1070(T)
      (=DSM 45226(T)=CCUG 56401(T)).

PMID- 19406810
TI  - Lacibacter cauensis gen. nov., sp. nov., a novel member of the phylum
      Bacteroidetes isolated from sediment of a eutrophic lake.
AB  - A novel strain, NJ-8(T), was isolated from sediment of the eutrophic Taihu Lake
      (China) and was subjected to a taxonomic study by using a polyphasic approach.
      The novel strain was aerobic and formed orange-pigmented colonies on R2A agar.
      Cells were Gram-negative single rods that were motile by means of gliding.
      Phylogenetic analysis based on 16S rRNA gene sequences showed that strain NJ-8(T)
      belonged to the phylum Bacteroidetes, with Niastella yeongjuensis DSM 17621(T)
      (92.3 % gene sequence similarity) and Niastella koreensis DSM 17620(T) (92.0 %
      similarity) as its closest relatives. The major fatty acids (>5 % of the total)
      were iso-C(15 : 0) (27.8 %), iso-C(15 : 1) G (15.4 %), iso-C(17 : 0) 3-OH (14.5
      %) and summed feature 3 (comprising C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH;
      13.9 %). The genomic DNA G+C content was 46.6 mol%. Based on molecular and
      phenotypic data, strain NJ-8(T) is considered to represent a novel species of a
      new genus, for which the name Lacibacter cauensis gen. nov., sp. nov. is
      proposed. The type strain of the type species of the genus, Lacibacter cauensis,
      is NJ-8(T) (=CGMCC 1.7271(T)=NBRC 104930(T)).

PMID- 19406811
TI  - Oceanicola pacificus sp. nov., isolated from a deep-sea pyrene-degrading
      consortium.
AB  - A taxonomic study was carried out on a Gram-negative, rod-shaped, non-motile,
      halophilic bacterium, designated strain W11-2B(T), which was isolated from a
      pyrene-degrading consortium that was enriched from sediment from the Pacific
      Ocean. Growth was observed at salinities of 0.5-10 % and at temperatures of 10-41
      degrees C. Strain W11-2B(T) was unable to degrade Tween 80 or gelatin. 16S rRNA
      gene sequence comparisons showed that strain W11-2B(T) was related most closely
      to Oceanicola nanhaiensis SS011B1-20(T) (95.8 % similarity) and Oceanicola
      batsensis HTCC2597(T) (95.7 %); levels of 16S rRNA gene sequence similarity
      between strain W11-2B(T) and the type strains of other species tested were below
      95.2 %. The dominant fatty acids of strain W11-2B(T) were C(18 : 1)omega7c (32.1
      % of the total), C(19 : 0) cyclo (20.9 %), C(18 : 1)omega7c 11-methyl (19.5 %),
      C(18 : 0) (7.3 %), C(17 : 0) (6.6 %) and C(16 : 0) (3.8 %). The G+C content of
      the chromosomal DNA was 64.6 mol%. The above data were in good agreement with
      those of members of the genus Oceanicola. Based on morphology, physiology, fatty
      acid composition and 16S rRNA gene sequence data, strain W11-2B(T) is considered
      to represent a novel species of the genus Oceanicola, for which the name
      Oceanicola pacificus sp. nov. is proposed. The type strain is W11-2B(T) (=CCTCC
      AB 208224(T)=LMG 24619(T)=MCCC 1A01034(T)).

PMID- 19406812
TI  - Flavobacterium sasangense sp. nov., isolated from a wastewater stream polluted
      with heavy metals.
AB  - A Gram-negative, rod-shaped bacterium, designated strain YC6274(T), was isolated
      from a stream (Sasang) carrying wastewater polluted with heavy metals in Busan,
      Korea. Growth was observed at 10-35 degrees C (optimum, 30 degrees C) and pH 6.0
      9.5 (optimum, pH 7.5-8.0). Comparative 16S rRNA gene sequence analyses showed
      that the strain was most closely related to Flavobacterium cucumis R2A45-3(T)
      (96.6 % similarity), F. aquatile ATCC 11947(T) (93.7 %), F. croceum EMB47(T)
      (93.3 %), F. indicum GPTSA100-9(T) (93.3 %) and F. terrigena DS-20(T) (93.2 %).
      Sequence similarities with strains of other Flavobacterium species with validly
      published names were lower than 93.0 %. Phylogenetic analysis based on the 16S
      rRNA gene sequence showed that strain YC6274(T) formed a distinct phyletic
      lineage within the genus Flavobacterium. The predominant fatty acids of strain
      YC6274(T) were iso-C(15 : 0), iso-C(16 : 0), iso-C(15 : 1) G, iso-C(17 : 0) 3-OH,
      iso-C(16 : 0) 3-OH and iso-C(15 : 0) 3-OH. The G+C content of the genomic DNA was
      32.5 mol% and the major quinone was MK-6. On the basis of phenotypic,
      chemotaxonomic and molecular data, it is clear that strain YC6274(T) represents a
      novel species within the genus Flavobacterium, for which the name Flavobacterium
      sasangense sp. nov. is proposed. The type strain is YC6274(T) (=KCTC 22246(T)
      =DSM 21067(T)).

PMID- 19406813
TI  - Gracilimonas tropica gen. nov., sp. nov., isolated from a Synechococcus culture.
AB  - An irregular, long, rod-shaped marine bacterium, designated CL-CB462(T), was
      isolated from a Synechococcus culture, which was established from surface water
      from the tropical Pacific Ocean. The physiological and biochemical features,
      fatty acid profile and phylogenetic position based on 16S rRNA gene sequences
      were investigated for the novel strain. Phylogenetic analysis of the 16S rRNA
      gene sequence showed that the closest relatives of strain CL-CB462(T) were
      Balneola vulgaris and Balneola alkaliphila. Strain CL-CB462(T) formed a robust
      clade with members of the genus Balneola in all phylogenetic trees constructed by
      three different methods. However, the 16S rRNA gene sequence similarity was very
      low (91.3-91.5 % similarity) and phenotypic and physiological features could
      clearly differentiate strain CL-CB462(T) from the genus Balneola. Cells of the
      novel strain were non-motile and spore-forming. The strain was able to grow at 1
      20 % (w/v) (optimum of 3-6 %) sea salt concentration, at temperatures of 20-40
      degrees C and between pH 6 and 10. The fatty acids were dominated by 15 : 0 iso
      (41.2 %) and 17 : 1omega9c iso (21.4 %). The DNA G+C content was 42.7 mol%. Based
      on polyphasic evidence, strain CL-CB462(T) was considered to represent a new
      genus. The name Gracilimonas tropica gen. nov., sp. nov. is proposed for the type
      strain of the type species (CL-CB462(T)=KCCM 90063(T)=DSM 19535(T)).

PMID- 19406814
TI  - Marinobacterium nitratireducens sp. nov. and Marinobacterium sediminicola sp.
      nov., isolated from marine sediment.
AB  - Two strains, CN44(T) and CN47(T), isolated from marine sediment of the East China
      Sea, were characterized by using a polyphasic approach. The isolates were Gram
      negative, strictly aerobic, non-spore-forming rods. The chemotaxonomic
      characteristics of these isolates included the presence of C(18 : 1)omega7c, C(16
      : 0), iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c and C(10 : 0) 3-OH as the major
      cellular fatty acids and Q-8 as the predominant ubiquinone. The DNA G+C contents
      of strains CN44(T) and CN47(T) were 62.5 and 56.3 mol%, respectively.
      Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain
      CN44(T) was related to members of the genus Marinobacterium. The most closely
      related described organism was the type strain of Marinobacterium rhizophilum
      (95.3 % sequence similarity). Strain CN47(T) showed the highest sequence
      similarity to the type strain of Marinobacterium stanieri (97.8 %) and <97 %
      similarity to other type strains of described Marinobacterium species. The level
      of DNA-DNA relatedness between strain CN47(T) and M. stanieri DSM 7027(T) was 46
      %. On the basis of phenotypic and genotypic properties, strains CN44(T) and
      CN47(T) represent two novel species within the genus Marinobacterium, for which
      the names Marinobacterium nitratireducens sp. nov. (type strain, CN44(T) =CGMCC
      1.7286(T) =JCM 15523(T)) and Marinobacterium sediminicola sp. nov. (type strain,
      CN47(T) =CGMCC 1.7287(T) =JCM 15524(T)) are proposed.

PMID- 19406815
TI  - Sphingomonas japonica sp. nov., isolated from the marine crustacean Paralithodes
      camtschatica.
AB  - A Sphingomonas-like bacterium, strain KC7(T), was isolated from a marine
      crustacean specimen obtained from the Sea of Japan and subjected to a polyphasic
      study. Comparative 16S rRNA gene sequence analysis positioned the novel strain in
      the genus Sphingomonas as an independent lineage adjacent to a subclade
      containing Sphingomonas trueperi LMG 2142(T), Sphingomonas pituitosa EDIV(T) and
      Sphingomonas azotifigens NBRC 15497(T). Strain KC7(T) shared highest 16S rRNA
      gene sequence similarity (96.1 %) with S. trueperi LMG 2142(T), Sphingomonas
      dokdonensis DS-4(T) and S. azotifigens NBRC 15497(T); similarities to strains of
      other recognized Sphingomonas species were lower (96.0-93.9 %). The strain
      contained sphingoglycolipid and the predominant fatty acids were C(16 : 1), C(16
      : 0) and C(18 : 1); 2-OH C(14 : 0) was the major 2-hydroxy fatty acid.
      Previously, these lipids have been found to be characteristic of members of the
      genus Sphingomonas sensu stricto. On the basis of phylogenetic analysis and
      physiological and biochemical characterization, strain KC7(T) represents a novel
      species of the genus Sphingomonas, for which the name Sphingomonas japonica sp.
      nov. is proposed. The type strain is KC7(T) (=KMM 3038(T) =NRIC 0738(T) =JCM
      15438(T)).

PMID- 19406816
TI  - Hymenobacter daecheongensis sp. nov., isolated from stream sediment.
AB  - A Gram-negative, strictly aerobic, non-spore-forming, rod-shaped, red-pink
      bacterium, designated strain Dae14(T), was isolated from stream sediment
      collected near Daecheong Dam, South Korea, and its taxonomic position was
      investigated by using a polyphasic approach. Phylogenetic analysis of 16S rRNA
      gene sequences showed that strain Dae14(T) belonged to the genus Hymenobacter.
      Sequence similarities between strain Dae14(T) and the type strains of
      Hymenobacter species with validly published names ranged from 91.3 to 94.3 %. The
      predominant cellular fatty acids of strain Dae14(T) were iso-C(15 : 0), C(16 :
      1)omega5c, summed feature 5 (iso-C(17 : 1) I and/or anteiso-C(17 : 1) B) and iso
      C(16 : 0). The DNA G+C content was 62.2 mol%. Results of phylogenetic,
      chemotaxonomic and phenotypic characterization indicated that strain Dae14(T) can
      be distinguished from all known Hymenobacter species and represents a novel
      species, for which the name Hymenobacter daecheongensis sp. nov. is proposed,
      with Dae14(T) (=KCTC 22258(T)=LMG 24498(T)) as the type strain.

PMID- 19406817
TI  - Haliea rubra sp. nov., a member of the Gammaproteobacteria from the Mediterranean
      Sea.
AB  - A novel aerobic, Gram-negative bacterium, designated strain CM41_15a(T), was
      isolated from the surface of coastal waters of the north-western Mediterranean
      Sea. Cells were non-motile straight rods that formed red colonies on marine agar
      medium. The G+C content of the genomic DNA was 65 mol %. Phylogenetic analysis of
      the 16S rRNA gene sequence placed the strain in the genus Haliea within the class
      Gammaproteobacteria. On the basis of the 16S rRNA gene sequence comparison and
      physiological and biochemical characteristics, strain CM41_15a(T) represents a
      novel species, for which the name Haliea rubra sp. nov. is proposed. The type
      strain is CM41_15a(T) (=DSM 19751(T)=CIP 109758(T)=MOLA 104(T)).

PMID- 19406818
TI  - Transfer of Teichococcus ludipueritiae and Muricoccus roseus to the genus
      Roseomonas, as Roseomonas ludipueritiae comb. nov. and Roseomonas rosea comb.
      nov., respectively, and emended description of the genus Roseomonas.
AB  - Phylogenetic analyses based on 16S rRNA gene sequences revealed that Teichococcus
      ludipueritiae and Muricoccus roseus are closely related to the species of the
      genus Roseomonas. The type strain of Teichococcus ludipueritiae, 170/96(T),
      exhibited 16S rRNA gene sequence similarity levels of 96.4 % to Roseomonas
      cervicalis ATCC 49957(T), 95.0 % to Roseomonas aquatica TR53(T), 94.5 % to
      Muricoccus roseus 173/96(T), 93.4 % to Roseomonas mucosa ATCC BAA-692(T) and 93.5
      % to Roseomonas gilardii subsp. gilardii ATCC 49956(T), while Muricoccus roseus
      173/96(T) showed 16S rRNA gene sequence similarity values of 95.7 % to R. mucosa
      ATCC BAA-692(T), 95.7 % to R. aquatica TR53(T) and 95.3 % to R. gilardii subsp.
      gilardii ATCC 49956(T) and R. gilardii subsp. rosea ATCC BAA-691(T). Different
      phylogenetic analysis methods (neighbour-joining, maximum-likelihood and maximum
      parsimony) confirmed that both species are within the Roseomonas branch. Neither
      polyamine patterns (spermidine predominant) nor major characteristics in the
      polar lipid profiles distinguished the two species from representatives of the
      genus Roseomonas. The fatty acid composition of the two species exhibited
      alphaproteobacterial characteristics but, like Roseomonas species, they also
      showed considerable amounts of the rarely encountered C(18 : 1) 2-OH. On the
      other hand, they showed some phenotypic differences, but their features are
      compatible with the transfer of these two species to the genus Roseomonas. We
      propose the reclassification of Teichococcus ludipueritiae and Muricoccus roseus
      as Roseomonas ludipueritiae comb. nov. (type strain 170/96(T) =CIP 107418(T) =DSM
      14915(T)) and Roseomonas rosea comb. nov. (type strain 173/96(T) =CIP 107419(T)
      =DSM 14916(T)), respectively. Emended descriptions of the genus Roseomonas and
      the species Roseomonas gilardii (and its subspecies Roseomonas gilardii subsp.
      gilardii and Roseomonas gilardii subsp. rosea), Roseomonas aquatica, Roseomonas
      cervicalis, Roseomonas mucosa and Roseomonas lacus are provided.

PMID- 19406819
TI  - Reclassification of Leptospira meyeri serovar Perameles to Leptospira interrogans
      serovar Perameles through serological and molecular analysis: evidence of a need
      for changes to current procedures in Leptospira taxonomy.
AB  - It has been recognized that there is heterogeneity among Leptospira isolates in
      culture collections worldwide, causing confounding results for researchers
      utilizing these organisms; one such culture is Leptospira meyeri serovar
      Perameles. The serovar reference strain Bandicoot 343 was previously identified
      to the species level by DNA-DNA hybridization; however, subsequent published
      studies demonstrated results that contradicted the initial speciation. In this
      study, initial serological testing was performed with isolates from the culture
      collections of the Centers for Disease Control (CDC), Atlanta, USA (strain
      Lepto0214), and the WHO/FAO/OIE Collaborating Centre for Reference and Research
      on Leptospirosis, Brisbane, Australia (strain Bandicoot 343), and the original
      serovar Perameles hyperimmune antiserum produced in 1964. The results indicated
      that strain Lepto0214 was not serologically reactive to the antiserum. However,
      further investigations revealed an alternative serovar Perameles strain held in
      the CDC collection (Lepto0213) that yielded titres against the antiserum. 16S
      rRNA gene sequencing of the three strains revealed that Lepto0214 had significant
      sequence similarity with previously sequenced L. meyeri strains; however, strains
      Lepto0213 and Bandicoot 343 had significant similarity with Leptospira
      interrogans strains. 16S rRNA gene sequencing results were confirmed by pulsed
      field gel electrophoresis; Lepto0214 had a pattern similar to that of L. meyeri
      serovar Hardjo strain Went 5, and the pattern differed significantly from those
      of Lepto0213 and Bandicoot 343. This research provides evidence for the
      reclassification of serovar Perameles from L. meyeri to L. interrogans. This
      reclassification highlights a need for changes to how reference Leptospira
      serovars are identified, disseminated and stored, with the aim of reducing
      heterogeneity of reference strains between culture collections.

PMID- 19406820
TI  - Marinoscillum gen. nov., a member of the family 'Flexibacteraceae', with
      Marinoscillum pacificum sp. nov. from a marine sponge and Marinoscillum
      furvescens nom. rev., comb. nov.
AB  - A novel strain, designated MRN461(T), was isolated from a marine sponge in
      Micronesia. The 16S rRNA gene sequence of the isolate showed 95.6 % similarity
      with that of 'Microscilla furvescens' IFO (now NBRC) 15994. Phylogenetic analysis
      revealed that the isolate and 'Microscilla furvescens' IFO 15994 formed a
      distinct phyletic line within the family 'Flexibacteraceae'. Cells of strain
      MRN461(T) were Gram-negative, long filamentous rods, motile by gliding. Growth
      was observed at 15-40 degrees C (optimum, 33 degrees C), at pH 5.0-9.5 (optimum,
      pH 7.5) and in the presence of 0.5-7.0 % sea salts (optimum, 2.5 %). The major
      isoprenoid quinone was MK-7. The dominant fatty acids were summed feature 3
      (comprising iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c; 34.8 %), C(16 : 1)omega5c
      (21.6 %) and iso-C(16 : 1) (19.8 %). The DNA G+C content was 41.5 mol%. On the
      basis of evidence from our polyphasic taxonomic study, strain MRN461(T) is
      classified within a novel genus and species in the family 'Flexibacteraceae', for
      which the name Marinoscillum pacificum gen. nov., sp. nov. is proposed. The type
      strain of Marinoscillum pacificum is strain MRN461(T) (=KCCM 42325(T) =JCM
      14064(T)). The misclassified species '[Microscilla] furvescens' is transferred to
      the new genus as Marinoscillum furvescens (ex Lewin 1969) nom. rev., comb. nov.,
      with LMG 13023(T) (=DSM 4134(T) =ATCC 23129(T) =NBRC 15994(T)) as the type
      strain.

PMID- 19406821
TI  - Phaeobacter caeruleus sp. nov., a blue-coloured, colony-forming bacterium
      isolated from a marine electroactive biofilm.
AB  - Three isolates (LMG 24369(T), LMG 24370 and R-26156) obtained from a marine
      electroactive biofilm that was grown on a cathodically polarized electrode were
      investigated by using a polyphasic taxonomic approach. Whole-cell fatty acid
      methyl ester and 16S rRNA gene sequence analyses indicated that the isolates were
      members of the genus Phaeobacter, class Alphaproteobacteria. Genotypic and
      phenotypic analyses demonstrated that the three isolates represent a novel
      species of the genus Phaeobacter, for which the name Phaeobacter caeruleus sp.
      nov. is proposed. The type strain is LMG 24369(T) (=CCUG 55859(T)). The DNA G+C
      content of strain LMG 24369(T) is 63.6 mol%.

PMID- 19406822
TI  - Alkalibacterium thalassium sp. nov., Alkalibacterium pelagium sp. nov.,
      Alkalibacterium putridalgicola sp. nov. and Alkalibacterium kapii sp. nov.,
      slightly halophilic and alkaliphilic marine lactic acid bacteria isolated from
      marine organisms and salted foods collected in Japan and Thailand.
AB  - We describe 10 new strains of marine lactic acid bacteria isolated from decaying
      marine algae, decaying seagrass, raw fish, salted fish and salted and fermented
      shrimp paste ('ka-pi') collected from a temperate area of Japan and Thailand. The
      isolates are Gram-positive and non-sporulating. They have motility with
      peritrichous flagella depending on the strains. They lack catalase and quinones.
      Under anaerobic conditions, lactate yields were 64-93 % of the glucose consumed;
      residual products were formate, acetate and ethanol with a molar ratio of
      approximately 2 : 1 : 1. The pH of the fermentation medium markedly affected the
      product composition; at higher pH, the yield of lactate decreased (15-48 % at pH
      9.0) and yields of other products increased, retaining the molar ratio. Under
      aerobic conditions, acetate and lactate were produced from carbohydrates and
      related compounds. The isolates were slightly halophilic, highly halotolerant and
      alkaliphilic. The optimum NaCl concentration for growth ranged between 0.5 and
      4.0 % (w/v), depending on the strain, with a growth range of between 0 and 17-21
      % (11 % for one isolate). The optimum pH for growth ranged between 8.0 and 9.5,
      with a growth range of 6.0-11.0, depending on the strains. Comparative sequence
      analysis of the 16S rRNA genes revealed that the isolates occupied three
      phylogenetic positions within the genus Alkalibacterium, showing 97.1-99.8 %
      similarity to Alkalibacterium indicireducens. DNA-DNA hybridization values (<46
      %) among the 10 isolates and phylogenetically related taxa resulted in the
      identification of four genomic species (designated groups GS1-GS4). The G+C
      contents of the DNA were 41.7 mol% (group GS1), 42.2 mol% (group GS2), 41.0-43.0
      mol% (group GS3) and 38.4-39.4 mol% (group GS4). The cell-wall peptidoglycan was
      type A4beta, Orn-d-Asp, for three genomic species (groups GS1, GS2 and GS3), and
      type A4beta, Orn-d-Glu, for the remaining species (group GS4). The major
      components of cellular fatty acids were C(16 : 0), C(16 : 1)omega9c and C(18 :
      1)omega9c (oleic acid). On the bases of phenotypic characteristics, genetic
      distinctiveness and phylogenetic affiliations, the four genomic species, groups
      GS1, GS2, GS3 and GS4, were classified as four novel species within the genus
      Alkalibacterium, for which the names Alkalibacterium thalassium sp. nov.,
      Alkalibacterium pelagium sp. nov., Alkalibacterium putridalgicola sp. nov. and
      Alkalibacterium kapii sp. nov., respectively, are proposed. The respective type
      strains are T117-1-2(T) (=DSM 19181(T)=NBRC 103241(T)=NRIC 0718(T)), T143-1-1(T)
      (=DSM 19183(T)=NBRC 103242(T)=NRIC 0719(T)), T129-2-1(T) (=DSM 19182(T)=NBRC
      103243(T)=NRIC 0720(T)) and T22-1-2(T) (=DSM 19180(T)=NBRC 103247(T)=NRIC
      0724(T)).

PMID- 19406823
TI  - Brevibacillus panacihumi sp. nov., a beta-glucosidase-producing bacterium.
AB  - Two Gram-positive-staining, endospore-forming, rod-shaped, motile bacteria,
      strains DCY35(T) and C17, were isolated from soil of a ginseng field in South
      Korea and were characterized in order to determine their taxonomic positions. 16S
      rRNA gene sequence analysis revealed that the two strains belonged to the family
      Paenibacillaceae; strain DCY35(T) showed highest levels of similarity to strain
      C17 (99.9 %), Brevibacillus invocatus LMG 18962(T) (98.9 %), B. centrosporus DSM
      8445(T) (98.0 %), B. borstelensis DSM 6347(T) (97.6 %), B. formosus DSM 9885(T)
      (97.4 %), B. agri DSM 6348(T) (97.3 %), B. brevis DSM 30(T) (97.3 %) and B.
      levickii LMG 22481(T) (97.0 %). Chemotaxonomic analyses revealed that strains
      DCY35(T) and C17 possess menaquinone MK-7, common to members of the genus
      Brevibacillus, and that the predominant fatty acids were iso-C(15 : 0) (37.3 % of
      the total), anteiso-C(15 : 0) (32.9 %), iso-C(14 : 0) (11.8 %) and iso-C(16 : 0)
      (6.5 %). The results of physiological and biochemical tests clearly demonstrated
      that strains DCY35(T) and C17 represent a distinct species. Based on these data,
      the two strains are considered to represent a novel species of the genus
      Brevibacillus, for which the name Brevibacillus panacihumi sp. nov. is proposed.
      The type strain is DCY35(T) (=KCTC 13206(T) =JCM 15085(T)).

PMID- 19406824
TI  - Wickerhamomyces queroliae sp. nov. and Candida jalapaonensis sp. nov., two yeast
      species isolated from Cerrado ecosystem in North Brazil.
AB  - Two novel yeast species, Wickerhamomyces queroliae sp. nov. and Candida
      jalapaonensis sp. nov., were isolated, respectively, from larvae of Anastrepha
      mucronata (Diptera: Tephritidae) collected from ripe fruit of Peritassa
      campestris ('Bacupari', Hippocrateaceae) and from flowers of Centropogon cornutus
      (Campanulaceae) in the Cerrado ecosystem of the state of Tocantins, Brazil.
      Analysis of the D1/D2 large-subunit rRNA gene sequences placed W. queroliae in
      the Wickerhamomyces clade near Wickerhamomyces ciferri and Candida silvicultrix.
      Candida jalapaonensis belongs to the Wickerhamiella clade and is related to
      Candida drosophilae. The type strain of Wickerhamomyces queroliae is UFMG-05
      T200.1(T) (=CBS 10936(T)=NRRL Y-48478(T)) and the type strain of Candida
      jalapaonensis is UFMG-03-T210(T) (=CBS 10935(T)=NRRL Y-48477(T)).

PMID- 19406825
TI  - Candida mengyuniae sp. nov., a metsulfuron-methyl-resistant yeast.
AB  - A metsulfuron-methyl-resistant yeast strain, JHL(T), was isolated from
      metsulfuron-methyl-contaminated soil collected in Jiangsu Province, China.
      Through morphological and physiological analysis as well as a molecular
      phylogenetic analysis based on the 26S rRNA gene D1/D2 region and internal
      transcribed spacer (ITS), this strain, which forms a clade with Candida
      vartiovaarae and a teleomorphic species, Williopsis saturnus, was revealed to
      represent a novel species in the genus Candida. The name Candida mengyuniae sp.
      nov. (type strain JHL(T)=CGMCC 2.3681(T)=CBS 10845(T)) is proposed for this novel
      species.

PMID- 19406827
TI  - Legitimacy is an essential concept of the International Code of Nomenclature of
      Prokaryotes - a major revision of the Code is called for.
AB  - Tindall [Int J Syst Evol Microbiol 58 (2008), 1979-1986] claimed that the
      International Code of Nomenclature of Prokaryotes (the Code) creates a paradox in
      the application of the term 'legitimate' in relation to valid publication, that
      the term is dispensable and that the paradox would be resolved by revising the
      Code to avoid its use. Although it is not clearly explained in the Code, the
      concept of legitimacy is central to the proposal of names. Discarding the concept
      would fundamentally alter the conceptual structure of the Code and obscure
      significant distinctions in formal nomenclature. The text of the Code itself is
      not clear and a careful reading suggests that it would be enhanced by a critical
      overview involving textual revision and restructuring of some sections. The
      Judicial Commission is asked not to accept Tindall's suggested revision and it is
      proposed that the Editorial Board of the International Committee on Systematics
      of Prokaryotes re-examine the Code from first principles and make such revisions
      as will avoid in future the confusion, ambiguities and uncertainties indicated
      here.

PMID- 19406826
TI  - Delimitation of the species of the Debaryomyces hansenii complex by intron
      sequence analysis.
AB  - The delineation of species among strains assigned to Debaryomyces hansenii was
      examined using a gene genealogies-based approach in order to compare spliceosomal
      intron sequences found in four housekeeping genes (ACT1, TUB2, RPL31 and RPL33).
      This revealed four distinct groups of strains containing, respectively, D.
      hansenii var. hansenii CBS 767(T), D. hansenii var. fabryi CBS 789(T), Candida
      famata var. flareri CBS 1796(T) (the anamorph of D. hansenii var. fabryi CBS
      789(T)) and Debaryomyces tyrocola CBS 766(T), whose species status was no longer
      accepted. The sequence divergence between these groups, reaching in some cases
      over 20 %, unambiguously isolated the groups as separate taxa, leading to a
      proposal for the reinstatement of the originally described species D. hansenii
      CBS 767(T) and D. tyrocola CBS 766(T). The variety D. hansenii var. fabryi was
      further subdivided into two taxa, Debaryomyces fabryi CBS 789(T) and Candida
      flareri CBS 1796(T) (previously C. famata var. flareri and Blastodendrion
      flareri). The comparison of intron sequences therefore exposed cryptic species
      whose phenotypic traits are not distinguishable from known species, but which
      have significantly diverged from the genetic point of view. Hence, we describe
      the new taxon Debaryomyces macquariensis sp. nov. CBS 5571(T) is related to, but
      clearly distinct from, the Debaryomyces species mentioned above. The approach
      used in this work has also revealed the existence of populations within the newly
      delineated species D. hansenii and genetic exchanges between these populations,
      indicating an unexpected genetic diversity within this part of the genus
      Debaryomyces.

PMID- 19406828
TI  - Inverse correlation between HPSE gene single nucleotide polymorphisms and
      heparanase expression: possibility of multiple levels of heparanase regulation.
AB  - Heparanase is an endo-beta-glucuronidase that specifically cleaves the saccharide
      chains of heparan sulfate proteoglycans. Heparanase plays important roles in
      processes such as angiogenesis, tumor metastasis, tissue repair and remodeling,
      inflammation and autoimmunity. Genetic variations of the heparanase gene (HPSE)
      have been associated with heparanase transcription level. The present study was
      undertaken to identify haplotype or single nucleotide polymorphisms (SNPs)
      genotype combinations that correlate with heparanase expression both at the mRNA
      and protein levels. For this purpose, 11 HPSE gene SNPs were genotyped among 108
      healthy individuals. Five out of the eleven polymorphisms revealed an association
      between the SNPs and heparanase expression. SNP rs4693608 exhibited a strong
      evidence of association. Analysis of haplotypes distribution revealed that the
      combination of two SNPs (rs4693608 and rs4364254) disclosed the most significant
      result. This approach allowed segregation of possible genotype combinations to
      three groups that correlate with low (LR: GG-CC, GG-CT, GG-TT, GA-CC),
      intermediate (MR: GA-CT, GA-TT) and high (HR: AA-TT, AA-CT) heparanase
      expression. Unexpectedly, LR genotype combinations were associated with low mRNA
      expressions level and high heparanase concentration in plasma, while HR genotype
      combinations were associated with high expression of mRNA and low plasma protein
      level. Because the main site of activity of secreted active heparanase is the
      extracellular matrix and cell surface, the origin and functional significance of
      plasma heparanase remain to be investigated. The current study indicates that
      rs4693608 and rs4364254 SNPs are involved in the regulation of heparanase
      expression and provides the basis for further studies on the association between
      HPSE gene SNPs and disease outcome.

PMID- 19406829
TI  - Pivotal Advance: Eosinophilia in the MES rat strain is caused by a loss-of
      function mutation in the gene for cytochrome b(-245), alpha polypeptide (Cyba).
AB  - MES is a rat strain that spontaneously develops severe blood eosinophilia as a
      hereditary trait. Herein, we report that eosinophilia in MES rats is caused by a
      loss-of-function mutation in the gene for cytochrome b(-245), alpha polypeptide
      (Cyba; also known as p22(phox)), which is an essential component of the
      superoxide-generating NADPH oxidase complex. The MES rat has a deletion of four
      nucleotides, including the 5' splice donor GpT of intron 4 of the Cyba gene. As a
      consequence of the deletion, a 51-nucleotide sequence of intron 4 is incorporated
      into the Cyba transcripts. Leukocytes from the MES strain lack both CYBA protein
      and NADPH oxidase activity. Nevertheless, unlike patients with chronic
      granulomatous disease, who suffer from infections with pathogens due to similar
      genetic defects in NADPH oxidase, MES rats retain normal innate immune defense
      against Staphylococcus aureus infection. This is due to large quantities of
      peritoneal eosinophils in MES rats, which phagocytose and kill the bacteria. MES
      rat has a balance defect due to impaired formation of otoconia in the utricles
      and saccules. Eosinophilia of the MES rat was normalized by introduction of a
      normal Cyba transgene. The mechanisms by which impairment of NADPH oxidase leads
      to eosinophilia in the MES rat are elusive. However, our study highlights the
      essential role of NADPH oxidase in homeostatic regulation of innate immunity
      beyond conventional microbicidial functions.

PMID- 19406830
TI  - GM-CSF- and M-CSF-dependent macrophage phenotypes display differential dependence
      on type I interferon signaling.
AB  - M-CSF and GM-CSF are mediators involved in regulating the numbers and function of
      macrophage lineage populations and have been shown to contribute to macrophage
      heterogeneity. Type I IFN is an important mediator produced by macrophages and
      can have profound regulatory effects on their properties. In this study, we
      compared bone marrow-derived macrophages (BMM) and GM-CSF-induced BMM (GM-BMM)
      from wild-type and IFNAR1(-/-) mice to assess the contribution of endogenous type
      I IFN to the phenotypic differences between BMM and GM-BMM. BMM were capable of
      higher constitutive IFN-beta production, which contributed significantly to their
      basal transcriptome. Microarray analysis found that of the endogenous type I IFN
      regulated genes specific to either BMM or GM-BMM, 488 of these gene alterations
      were unique to BMM, while only 50 were unique to GM-BMM. Moreover, BMM displayed
      enhanced basal mRNA levels, relative to GM-BMM, of a number of genes identified
      as being dependent on type I IFN signaling, including Stat1, Stat2, Irf7, Ccl5,
      Ccl12, and Cxcl10. As a result of prior type I IFN "priming," upon LPS
      stimulation BMM displayed increased activation of the MyD88-independent IRF
      3/STAT1 pathways compared with GM-BMM, which correlated with the distinct
      cytokine/chemokine profiles of the two macrophage subsets. Furthermore, the
      autocrine type I IFN signaling loop regulated the production of the M1 and M2
      signature cytokines, IL-12p70 and IL-10. Collectively, these findings demonstrate
      that constitutive and LPS-induced type I IFN play significant roles in regulating
      the differences in phenotype and function between BMM and GM-BMM.

PMID- 19406831
TI  - Functional implication of BAFF synthesis and release in gangliosides-stimulated
      microglia.
AB  - BAFF is a recently identified member of the TNF ligand superfamily that plays a
      critical role in B cell differentiation, survival, and regulation of Ig
      production. In the present study, we examined whether BAFF is expressed in
      microglia, and the expression and release of BAFF are regulated by gangliosides.
      The results showed that BAFF was expressed and released in rat primary microglia
      as well as in BV-2 cells. Furthermore, its expression and release were increased
      by gangliosides stimulation and regulated by JAK-STAT, especially the STAT1- and
      STAT3-dependent signaling pathways. It was of particular interest to observe that
      SP600125 and SB203580, specific inhibitors of JNK and p38, did not inhibit BAFF
      synthesis but inhibited the release of sBAFF in gangliosides-treated cells by
      regulating furin expression, suggesting that the JNK and p38 signaling pathways
      regulate the release but not the synthesis of BAFF. Moreover, BV-2 cells
      expressed BAFF-R on their cell surface, and rat primary microglia expressed BAFF
      R and TACI on their cell surface. rBAFF increased the release of cytokines,
      especially IL-6, TNF-alpha, and IL-10, in rat primary microglia as well as in BV
      2 cells. These findings imply that BAFF secreted by microglia may play important
      roles in CNS inflammation by regulating microglia as well as infiltrated B cells.

PMID- 19406834
TI  - IL-21: a new player in the control of isotype switch in Peyer's patches.
AB  - Peyer's patches (PP) are lymphoid follicles of the small intestine containing
      predominantly IgA(+) B cells. In this JLB issue, IL-21 is reported to dampen TGF
      beta1-induced IgG2b but not IgA production by mouse B cells, possibly explaining
      why IgA(+) B cells predominate in PP.

PMID- 19406832
TI  - Involvement of TLR2 and TLR4 in  inflammatory immune responses induced by  fine
      and coarse ambient air particulate  matter.
AB  - Induction of proinflammatory mediators by alveolar macrophages exposed to ambient
      air particulate matter has been suggested to be a key factor in the pathogenesis
      of inflammatory and allergic diseases in the lungs. However, receptors and
      mechanisms underlying these responses have not been fully elucidated. In this
      study, we examined whether TLR2, TLR4, and the key adaptor protein, MyD88,
      mediate the expression of proinflammatory cytokines and chemokines by mouse
      peritoneal macrophages exposed to fine and coarse PM. TLR2 deficiency blunted
      macrophage TNF-alpha and IL-6 expression in response to fine (PM2.5), while not
      affecting cytokine-inducing ability of coarse NIST Standard Reference Material
      (SRM 1648) particles. In contrast, TLR4(-/-) macrophages showed inhibited
      cytokine expression upon stimulation with NIST SRM 1648 but exhibited normal
      responses to PM2.5. Preincubation with polymyxin B markedly suppressed the
      capacity of NIST SRM 1648 to elicit TNF-alpha and IL-6, indicating endotoxin as a
      principal inducer of cytokine responses. Overexpression of TLR2 in TLR2/4
      deficient human embryonic kidney 293 cells imparted PM2.5 sensitivity, as judged
      by IL-8 gene expression, whereas NIST SRM 1648, but not PM2.5 elicited IL-8
      expression in 293/TLR4/MD-2 transfectants. Engagement of TLR4 by NIST SRM 1648
      induced MyD88-independent expression of the chemokine RANTES, while TLR2-reactive
      NIST IRM PM2.5 failed to up-regulate this response. Consistent with the shared
      use of MyD88 by TLR2 and TLR4, cytokine responses of MyD88(-/-) macrophages to
      both types of air PM were significantly reduced. These data indicate differential
      utilization of TLR2 and TLR4 but shared use of MyD88 by fine and coarse air
      pollution particles.

PMID- 19406833
TI  - Liver X receptor agonist regulation of Th17  lymphocyte function in autoimmunity.
AB  - CD4+ Th17 cells are believed to play an important role in the development of a
      variety of autoimmune diseases including EAE, an animal model of MS. Previously,
      we and others demonstrated that LXR agonists suppressed the activation of primary
      glial cells and blocked the development of EAE. The present studies demonstrated
      that the LXR agonist T0901317 suppressed IL-17A expression from splenocytes
      derived from Valpha2.3/Vbeta8.2 TCR transgenic mice and from MOG(35-55)-immunized
      C57BL/6 mice. Furthermore, in vitro treatment with IL-23 alone or in combination
      with MOG(35-55) induced IL-17A expression from splenocytes derived from MOG(35
      55)-immunized mice, and T0901317 blocked this induction. In vitro treatment with
      the LXR agonist suppressed IL-23R expression by splenocytes. In addition, in vivo
      treatment with the LXR agonist suppressed IL-17A and IL-23R mRNA and protein
      expression in EAE mice. These studies suggest that LXR agonists suppress EAE, at
      least in part by suppressing IL-23 signaling. Recent studies indicate that the
      cytokines IL-21 and IL-22 are produced by Th17 cells and modulate immune
      responses. Our studies demonstrate that the LXR agonist T0901317 suppressed
      MOG(35-55)-induced expression of IL-21 and IL-22 mRNA in splenocytes derived from
      MOG(35-55)-immunized mice. Finally, we demonstrate that the LXR agonist T0901317
      suppressed the development of EAE in an experimental paradigm involving treatment
      of established EAE. Collectively, these studies suggest that LXR agonists may be
      effective in the treatment of MS.

PMID- 19406836
TI  - Phosphodiesterase-4 inhibition and brain tumor growth.

PMID- 19406839
TI  - Does diabetes accelerate progression of calcific aortic stenosis?
AB  - AIMS: Calcific aortic valve stenosis (CAS) is an active disease like
      atherosclerosis. Effect of diabetes (D) on severity of CAS is not well
      documented. METHODS AND RESULTS: We retrospectively analysed 166 consecutive
      patients with CAS and multiple echocardiograms from January 1997 to March 2005.
      Aortic valve area (AVA) was measured using the continuity equation. CAS severity
      was categorized using AVA. D and non-D patients were compared for differences in
      sex, hypertension, smoking, statin use using chi(2) tests. Comparisons between D
      and non-D for changes in AVA per year were performed using ANOVA. Study cohort
      included 166 males with age 70 +/- 9 years, of which 72 (43%) had D. Baseline CAS
      was mild in 66 subjects, moderate in 75, and severe in 25. D subjects smoked less
      (P = 0.02), but all other variables were similar (P > 0.05). The interaction
      between D and baseline CAS severity was significant (P = 0.0191), indicating
      comparisons should be viewed by baseline CAS severity. D had significantly larger
      change in AVA than non-D (P = 0.0016) for those with moderate CAS at baseline
      only. Adjusting for statin use did not alter the results. CONCLUSION: CAS
      severity progresses faster in D than in non-D in subjects with moderate CAS at
      baseline. Statins do not affect progression of CAS.

PMID- 19406837
TI  - E2F1 expression is deregulated and plays an oncogenic role in sporadic Burkitt's
      lymphoma.
AB  - Current treatments of sporadic Burkitt's lymphoma (sBL) are associated with
      severe toxicities. A better understanding of sBL formation would facilitate
      development of less toxic therapies. The etiology of sBL remains, however,
      largely unknown, C-MYC up-regulation being the only lesion known to occur in all
      sBL cases. Several studies examining the role of C-MYC in the pathogenesis of BL
      have concluded that C-MYC translocation is not the only critical event and that
      additional unidentified factors are expected to be involved in the formation of
      this tumor. We herein report that a gene distinct from C-MYC, E2F1, is involved
      in the formation of all or most sBL tumors. We found that E2F1 is highly
      expressed in Burkitt's lymphoma cell lines and sBL lymphoma specimens. Our data
      indicate that its elevated expression is not merely the consequence of the
      presence of more cycling cells in this tumor relative to other cell lines or to
      other neoplasias. In fact, we show that reduction of its expression in sBL cells
      inhibits tumor formation and decreases their proliferation rate. We also provide
      data suggesting that E2F1 collaborates with C-MYC in sBL formation. E2F1
      expression down-regulation did not affect, however, the proliferation of human
      primary diploid fibroblasts. Because E2F1 is not needed for cell proliferation of
      normal cells, our results reveal E2F1 as a promising therapeutic target for sBL.

PMID- 19406838
TI  - Vascular endothelial function predicts mortality risk in patients with advanced
      ischaemic chronic heart failure.
AB  - AIMS: Endothelial function is impaired in advanced chronic heart failure (ACHF)
      patients. We explored a possible association between endothelial function and
      subsequent mortality risk in ACHF. METHODS AND RESULTS: We prospectively assessed
      brachial flow-mediated dilation (FMD) in 82 consecutive New York Heart
      Association class IV ischaemic ACHF patients with a mean left ventricular
      ejection fraction (LVEF) of 22 +/- 3%. Following overnight fasting and
      discontinuation of all medications for > or = 12 h, percent increase in FMD
      (%FMD) and nitroglycerin-mediated vasodilation were assessed using linear array
      ultrasound. All patients were followed for 14 +/- 2 months for adverse
      cardiovascular events, including death, hospitalization for CHF exacerbation, or
      myocardial infarction. Patients were divided into two groups: those with an FMD
      lesser than or equal to the median %FMD of 4.6% (n = 41) and those with an FMD
      above the median (n = 41). Both groups were comparable regarding cardiovascular
      risk factors, LVEF, and concomitant medications. During follow-up, 22 (53.6%)
      patients with FMD lesser than or equal to the median had composite adverse
      cardiovascular events compared with only eight patients (19.5%) with FMD above
      the median (P < 0.01). Furthermore, fiver deaths (12.1%) occurred in patients
      with FMD lesser than or equal to the median, compared with no deaths in patients
      with FMD above the median (P < 0.03). Cox regression analyses revealed that FMD
      was an independent predictor for these events. CONCLUSION: Flow-mediated dilation
      is associated with increased mortality risk in ischaemic ACHF patients.

PMID- 19406840
TI  - Cardiac re-synchronization therapy in a patient with isolated ventricular non
      compaction: a case report.
AB  - Isolated ventricular non-compaction (IVNC) is a rare, congenital, unclassified
      cardiomyopathy characterized by prominent trabecular meshwork and deep recesses.
      Major clinical manifestations of IVNC are heart failure, atrial and ventricular
      arrhythmias, and thrombo-embolic events. We describe a case of a 69-year-old
      woman in whom the diagnosis of IVNC was discovered late, whereas former
      echocardiographic examinations were considered normal. She was known for systolic
      left ventricular dysfunction for 3 years and then became symptomatic (NYHA III).
      In the past, she suffered from multiple episodes of deep vein thrombosis and
      pulmonary embolism. Electrocardiogram revealed a wide QRS complex, and
      transthoracic echocardiography showed typical apical thickening of the left and
      right ventricular myocardial wall with two distinct layers. The ratio of non
      compacted to compacted myocardium was >2:1. Cardiac MRI confirmed the
      echocardiographic images. Cerebral MRI revealed multiple ischaemic sequellae. In
      view of the persistent refractory, heart failure in medical treatment of patients
      with classical criteria for cardiac re-synchronization therapy, as well as the
      ventricular arrhythmias, a biventricular automatic intracardiac defibrillator
      (biventricular ICD) was implanted. The 2-year follow-up period was characterized
      by improvement of NYHA functional class from III to I and increasing in left
      ventricular function. We hereby present a case of IVNC with favourable outcome
      after biventricular ICD implantation. Cardiac re-synchronization therapy could be
      considered in the management of this pathology.

PMID- 19406841
TI  - Docosapentaenoic acid (DPA) is a critical determinant of cubic membrane formation
      in amoeba Chaos mitochondria.
AB  - Very long-chain polyunsaturated fatty acids (VLC-PUFAs), such as docosahexaenoic
      acid (DHA) and docosapentaenoic acid (DPA), have recently made it to the realm of
      "magical molecules" based on their multiple presumably beneficial effects in
      biological systems, making these PUFAs particularly interesting in biomedicine.
      Their specific biological functions, however, remain enigmatic. Here we provide
      evidence derived from studies in the amoeba Chaos that indicates a structural
      role for omega-6 DPA in cell membrane organization, which may help to explain the
      multiple diverse effects of VLC-PUFA in healthy and diseased states. Amoeba Chaos
      mitochondria undergo a remarkable and reversible morphological transition into
      cubic morphology on starvation. This morphological transition is reflected in
      major changes in fatty acid and lipid composition, as determined by gas liquid
      chromatography and mass spectrometry, in particular by a drastic increase in
      C22:5 modified phosphatidylcholine plasmalogen, phosphatidylethanolamine
      plasmalogen, and phosphatidylinositol species. Liposomes produced in vitro from
      lipids of starved amoeba cells show a high propensity to form hexagonal tubular
      and cubic morphologies. Addition of omega-6 DPA, but not of omega-3 DPA, to the
      cell culture also induced mitochondrial membrane transformation into cubic
      morphology in fed cells, demonstrating for the first time an important structural
      role of omega-6 DPA-containing lipids in cell membrane organization.

PMID- 19406842
TI  - Identification and characterization of oligonucleotides that inhibit Toll-like
      receptor 2-associated immune responses.
AB  - Toll-like receptors (TLRs) play important roles in the immune responses against
      invading microorganisms. Development of TLR antagonists is recognized as a
      promising direction in suppressing the associated inflammatory reactions of the
      TLRs. Aptamers are single-stranded RNA or DNA molecules isolated through an in
      vitro selection process. Using a novel molecular evolution strategy that combines
      immunoprecipitation (IP) with systematic evolution of ligands by exponential
      enrichment (SELEX), we developed an IP-SELEX selection method to facilitate the
      screening of high-affinity aptamers for the Toll-like receptor 2 (TLR2). Also,
      human TLR2 functional aptamers were identified and characterized using NF-kappaB
      reporter assays. Among the functional aptamers, the most effective, AP177, with a
      dissociation constant of 73 pM, was characterized with TLR2-expressing cells
      challenged with bacterial cells and purified ligands. The aptamer could
      effectively antagonize TLR2, significantly inhibit NF-kappaB activity, and
      suppress the secretion of the cytokines by >80%. In addition, the precise region
      within the functional aptamer that specifically bound TLR2 was resolved using
      aptamer microarray analysis. The results of functional assays showed that AP177
      acted as a TLR2 antagonist and may hold therapeutic potential in the treatment of
      diseases related to dysregulated TLR2 immune responses.

PMID- 19406844
TI  - cAMP opposes the glucose-mediated induction of the L-PK gene by preventing the
      recruitment of a complex containing ChREBP, HNF4alpha, and CBP.
AB  - Glucose-mediated activation of the L-type pyruvate kinase (L-PK) gene is
      repressed by cAMP, making this an excellent model for studying the mechanism by
      which these contrary signals regulate gene expression. Using the 832/13 rat
      insulinoma cell line, we demonstrate using RNA interference and chromatin
      immunoprecipitation that carbohydrate response element binding protein (ChREBP),
      hepatic nuclear factor 4alpha (HNF4alpha), and the coactivator CREB binding
      protein (CBP) are required for the glucose response of the L-PK gene and are
      recruited to the promoter by glucose. The cAMP agonist forskolin blocked the
      glucose-mediated induction of the L-PK gene in a PKA-dependent manner and blocked
      the recruitment of ChREBP, HNF4alpha, and CBP to the L-PK promoter, while
      simultaneously recruiting CBP to the cAMP-inducible gene, nuclear receptor
      subfamily 4, group A, member 2 (NR4A2). Overexpression of CBP, but not ChREBP,
      reversed the cAMP repression of the L-PK gene. In addition, CBP augmented the
      glucose response of the L-PK promoter. We conclude that cAMP and glucose
      signaling converge on a complex containing ChREBP, HNF4alpha, and CBP, and that
      cAMP acts by disrupting this transcriptional complex assembled by glucose-derived
      signals.

PMID- 19406845
TI  - The Atlanta Falcon and Tono-Bungay: dietary supplements as subprime drugs.

PMID- 19406843
TI  - Statin-induced muscle damage and atrogin-1 induction is the result of a
      geranylgeranylation defect.
AB  - Statins are widely used to treat hypercholesterolemia but can lead to a number of
      side effects in muscle, including rhabdomyolysis. Our recent findings implicated
      the induction of atrogin-1, a gene required for the development of muscle
      atrophy, in statin-induced muscle damage. Since statins inhibit many biochemical
      reactions besides cholesterol synthesis, we sought to define the statin-inhibited
      pathways responsible for atrogin-1 expression and muscle damage. We report here
      that lovastatin-induced atrogin-1 expression and muscle damage in cultured mouse
      myotubes and zebrafish can be prevented in the presence of geranylgeranol but not
      farnesol. Further, inhibitors of the transfer of geranylgeranyl isoprene units to
      protein targets cause statin muscle damage and atrogin-1 induction in cultured
      cells and in fish. These findings support the concept that dysfunction of small
      GTP-binding proteins lead to statin-induced muscle damage since these molecules
      require modification by geranylgeranyl moieties for their cellular localization
      and activity. Collectively, our animal and in vitro findings shed light on the
      molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be
      regulated by novel signaling pathways.

PMID- 19406846
TI  - "But many that are first shall be last; and the last shall be first".

PMID- 19406847
TI  - Regarding "Prostatic hormonal carcinogenesis is mediated by in situ estrogen
      production and estrogen receptor alpha signaling".

PMID- 19406850
TI  - Subacute implantable cardioverter defibrillator lead perforation: a potentially
      life-threatening event.
AB  - We describe a 74-year-old man presenting with a life-threatening left-sided
      haemothorax as a result of an implantable cardioverter defibrillator lead
      perforation occurring 1 month after implantation.

PMID- 19406849
TI  - In vitro activity of isavuconazole against Trichosporon, Rhodotorula, Geotrichum,
      Saccharomyces and Pichia species.
AB  - OBJECTIVES: The emergence of less common, but clinically important, fungal
      pathogens including the rare yeasts has contributed to the substantial morbidity
      and mortality observed in immunocompromised patients. These organisms can be
      resistant or refractory to existing antifungal agents. We sought to evaluate the
      activity of the new triazole isavuconazole against these difficult pathogens.
      METHODS: MICs of isavuconazole, voriconazole, posaconazole, fluconazole,
      amphotericin B and flucytosine were determined for 54 Trichosporon, 7 Geotrichum
      capitatum, 18 Saccharomyces cerevisiae, 11 Pichia and 14 Rhodotorula species in
      accordance with the M27-A2 reference method. Minimum fungicidal concentrations
      were also measured for each agent. RESULTS: Isavuconazole demonstrated excellent
      in vitro activity against each species tested. MIC(90) values ranged between
      0.125 and 0.25 mg/L against Trichosporon isolates, and between 0.03 and 0.5 mg/L
      against the other yeast tested. The geometric mean MICs of isavuconazole were
      similar to those of voriconazole and similar or less than those of posaconazole,
      fluconazole, amphotericin B and flucytosine for all species tested. This activity
      was also maintained against one Trichosporon asahii and nine Rhodotorula isolates
      that were resistant to fluconazole. CONCLUSIONS: Isavuconazole is a welcome
      addition to the growing antifungal armamentarium with potent in vitro activity
      against emerging yeast pathogens. Although this agent may be useful in the
      treatment of the rare yeasts, clinical data are needed to verify these results.

PMID- 19406851
TI  - Clinical outcome and tolerability of duloxetine in the treatment of major
      depressive disorder: a 12-week study with plasma levels.
AB  - Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor that
      has been recently approved for the treatment of major depressive disorder (MDD).
      However, little is known about the relationship between DLX plasma levels and
      clinical response. The aims of this open-label study were 1) to assess clinical
      outcome and tolerability of DLX by means of clinician and patient assessments and
      2) to evaluate the value of plasma DLX levels as predictors of clinical response
      and tolerability. This was a naturalistic, open-label study of 45 outpatients
      affected with MDD (16 men and 29 women), who received DLX at doses of 30-120
      mg/day and were evaluated at baseline (T0) and after 2, 4 and 12 weeks (T1-3).
      The assessments included the Hamilton Rating Scales for Depression (HRSD) and
      Anxiety (HRSA), Clinical Global Impression-Severity (CGI-S), Beck's Depression
      Inventory (BDI) and a mood visual analogue scale (VAS). Compared with T0, there
      were significant improvements in HRSD at T1, T2 and T3 (P < 0.001), in HRSA, CGI
      S and the self-administered BDI at T2 and T3 (P < 0.001), and in the VAS scores
      shown at T3 (P = 0.01). DLX treatment was safe and well tolerated. Plasma DLX
      levels at T2 ranged from 5 to 135 ng/mL (mean +/- SD = 53.56 +/- 39.45) and
      correlated almost significantly with the DLX dose (r = 0.35; P = 0.069). There
      was a significant curvilinear quadratic relationship between the improvement of
      HRSA scores and plasma DLX levels (R(2) = 0.27; P = 0.02). The incidence of
      anxiety or irritability was associated with the highest plasma levels. Our
      findings suggest that monitoring plasma DLX levels may be helpful in predicting
      better treatment responses and tolerability. The present data seem to suggest an
      optimal anxiolytic efficacy of DLX at intermediate plasma levels.

PMID- 19406853
TI  - Paradoxical enhancement of choice reaction time performance in patients with
      major depression.
AB  - The Cued Reinforcement Reaction Time (CRRT) task is a choice reaction time task
      in which rewards (points) are available if the subject responds quickly enough
      and are signalled with a certain probability by stimuli. Reaction times (RTs) are
      faster following stimuli predicting reward with a high probability than with a
      low probability. This RT difference is sensitive to manipulations and individual
      differences in the serotonin (5-HT) system, but the CRRT task performance has not
      yet been examined in patients with depression. We observed that patients
      performed better on the task than controls, as evidenced by a greater points
      score, a greater likelihood of reaching their reinforcement threshold and fewer
      errors. RT variability was reduced in the patients. No group differences in the
      effect of the conditioned stimuli on RTs were observed. Accounts of these
      surprising data are discussed, considering possible effects of antidepressant
      medication or task-dependent differences in selective attention. Regardless of
      precise mechanism, the results do indicate that depressed patients are not
      invariably impaired in motivational paradigms and that their RT performance in
      certain situations can be superior to that of controls.

PMID- 19406852
TI  - Striatal D2 receptor binding in 22q11 deletion syndrome: an [123I]IBZM SPECT
      study.
AB  - It has been hypothesised that in subjects with 22q11 deletion syndrome (22q11DS)
      disturbances of the dopamine (DA) system contribute to their increased risk for
      cognitive deficits and psychiatric problems. However, central DAergic
      neurotransmission in 22q11DS has not been investigated. We measured striatal D2
      receptor binding potential (D2R BP(ND)) using (S)-(-)-3-iodo-2-hydroxy-6-methoxy
      N-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide-single photon emission computed
      tomography ([123I]IBZM SPECT) in 12 adults with 22q11DS and 12 matched controls.
      Correlations between D2R BP(ND) and plasma prolactin (pPRL) levels were also
      determined. 22q11DS subjects and controls had similar D2R BP( ND). There was a
      positive correlation between D2R BP( ND) and pPRL values in controls, but no such
      relation was found in 22q11DS subjects. This study suggests that a 22q11 deletion
      does not affect striatal DAergic neurotransmission in the living human brain.
      However, the disturbed relationship between D2R BP(ND) and pPRL values suggests
      DAergic dysfunction at a different level. Further studies on DAergic function in
      extra-striatal brain regions and under challenged conditions are needed.

PMID- 19406854
TI  - Effects of delta9-tetrahydrocannabinol on reward and anxiety in rats exposed to
      chronic unpredictable stress.
AB  - Although cannabis derivatives produce clear subjective motivational responses in
      humans leading to drug-seeking behaviour, the reinforcing attributes of these
      subjective effects are difficult to define in experimental animals. The aim of
      this study was to examine how exposure to chronic unpredictable stress (CUS) will
      affect reward function and anxiety after acute administration of Delta(9)
      tetrahydrocannabinol (Delta(9)-THC) in rats. Male rats were exposed to either 10
      days of CUS or no stressor. Alterations in brain reward function were assessed
      with the intracranial self-stimulation (ICSS) paradigm, and anxiety responses
      were measured with the elevated plus maze. CUS did not affect baseline brain
      stimulation reward thresholds. Delta(9)-THC did not exhibit reinforcing actions
      in the ICSS paradigm neither in nonstressed nor in stressed animals. More
      importantly, in nonstressed animals, both the low and the high dose of Delta(9)
      THC exerted anxiolytic-like effects. In stressed animals, however, only the high
      dose of THC induced an anxiolytic-like response, whereas the low dose induced
      anxiogenic effects. The present results provide clear evidence for an anxiolytic
      effect of Delta(9)-THC both in stressed and in nonstressed animals, and indicate
      that environmental conditions, such as stressful experiences, do not alter the
      behavioural effects of Delta( 9)-THC in the ICSS paradigm.

PMID- 19406855
TI  - Health care for the elderly--perspectives in relation to implementation of
      results from intervention studies in Norway and Denmark.

PMID- 19406856
TI  - Abortion and depression: cause or confounding?

PMID- 19406860
TI  - The epidemiology of trauma, PTSD, and other posttrauma disorders.
AB  - Epidemiologic studies have reported that the majority of community residents in
      the United States have experienced posttraumatic stress disorder (PTSD)-level
      traumatic events, as defined in the DSM-IV. Only a small subset of trauma victims
      develops PTSD (<10%). Increased incidence of other disorders following trauma
      exposure occurs primarily among trauma victims with PTSD. Female victims of
      traumatic events are at higher risk for PTSD than male victims are. Direct
      evidence on the causes of the sex difference in the conditional risk of PTSD is
      unavailable. The available evidence suggests that the sex difference is not due
      to (a) the higher occurrence of sexual assault among females, (b) prior traumatic
      experiences, (c) preexisting depression or anxiety disorder, or (d) sex-related
      bias in reporting. Observed sex differences in anxiety, neuroticism, and
      depression, inducing effects of stressful experiences, might provide a
      theoretical context for further inquiry into the greater vulnerability of females
      to PTSD.

PMID- 19406861
TI  - Association between antioxidant vitamins and asthma outcome measures: systematic
      review and meta-analysis.
AB  - BACKGROUND: Epidemiological studies suggest that dietary intake of vitamins A, C
      and E may be associated with the occurrence of asthma. A systematic review and
      meta-analysis was conducted in accordance with MOOSE guidelines to determine
      whether vitamins A, C and E, measured as dietary intakes or serum levels, are
      associated with asthma. METHODS: MEDLINE, EMBASE, CINAHL, CAB abstracts and AMED
      (up to November 2007), conference proceedings and bibliographies of papers were
      searched to identify studies of asthma, wheeze or airway responsiveness in
      relation to intakes and serum concentrations of vitamins A, C and E. Pooled odds
      ratios (OR) or mean differences (MD) with 95% confidence intervals (CI) were
      estimated using random effects models. RESULTS: A total of 40 studies were
      included. Dietary vitamin A intake was significantly lower in people with asthma
      than in those without asthma (MD -82 microg/day, 95% CI -288 to -75; 3 studies)
      and in people with severe asthma than in those with mild asthma (MD -344
      microg/day; 2 studies). Lower quantile dietary intakes (OR 1.12, 95% CI 1.04 to
      1.21; 9 studies) and serum levels of vitamin C were also associated with an
      increased odds of asthma. Vitamin E intake was generally unrelated to asthma
      status but was significantly lower in severe asthma than in mild asthma (MD -1.20
      microg/day, 95% CI -2.3 to -0.1; 2 studies). CONCLUSIONS: Relatively low dietary
      intakes of vitamins A and C are associated with statistically significant
      increased odds of asthma and wheeze. Vitamin E intake does not appear to be
      related to asthma status.

PMID- 19406862
TI  - A SUPERMAN-like gene is exclusively expressed in female flowers of the dioecious
      plant Silene latifolia.
AB  - To elucidate the mechanism(s) underlying dioecious flower development, the
      present study analyzed a SUPERMAN (SUP) homolog, SlSUP, which was identified in
      Silene latifolia. The sex of this plant is determined by heteromorphic X and Y
      sex chromosomes. It was revealed that SlSUP is a single-copy autosomal gene
      expressed exclusively in female flowers. Introduction of a genomic copy of SlSUP
      into the Arabidopsis thaliana sup (sup-2) mutant complemented the excess-stamen
      and infertile phenotypes of sup-2, and the overexpression of SlSUP in transgenic
      Arabidopsis plants resulted in reduced stamen numbers as well as the suppression
      of petal elongation. During the development of the female flower in S. latifolia,
      the expression of SlSUP is first detectable in whorls 2 and 3 when the normal
      expression pattern of the B-class flowering genes was already established and
      persisted in the stamen primordia until the ovule had matured completely. In
      addition, significant expression of SlSUP was detected in the ovules, suggestive
      of the involvement of this gene in ovule development. Furthermore, it was
      revealed that the de-suppression of stamen development by infection of the S.
      latifolia female flower with Microbotryum violaceum was accompanied by a
      significant reduction in SlSUP transcript levels in the induced organs. Taken
      together, these results demonstrate that SlSUP is a female flower-specific gene
      and suggest that SlSUP has a positive role in the female flower developmental
      pathways of S. latifolia.

PMID- 19406864
TI  - Left ventricular mass increase is associated with cognitive decline and dementia
      in the elderly independently of blood pressure.
AB  - AIMS: Left ventricular (LV) mass increase is considered part of composite target
      organ damage in hypertension and an independent risk factor for cardiovascular
      (CV) events. This study was designed to explore whether left ventricular mass
      index (LVMI) is associated with cognitive decline and dementia in elderly
      subjects, independently of blood pressure (BP) levels. METHODS AND RESULTS: Four
      hundred subjects (mean age 79 +/- 6 years) were studied. Left ventricular mass
      was measured echocardiographically in accordance with American Society of
      Echocardiography and normalized for body height to the 2.7 (LVMI). Global
      cognitive function was evaluated with the mini-mental state examination (MMSE)
      (maximum score 30). Dementia was defined as an MMSE score <21. Arterial stiffness
      was evaluated as carotid-femoral pulse wave velocity by Complior. Prevalence of
      hypertension was 70% and diabetes mellitus was diagnosed in 25%. No significant
      differences in traditional CV risk factors were observed across LVMI quartiles.
      Mini-mental state examination showed an inverse trend across LVMI quartiles (the
      higher the LVMI, the lower the MMSE, P for trend <0.05); systolic and diastolic
      BP levels were not different across LVMI quartiles. In multivariable logistic
      regression models, including age, sex, BP levels, and use of antihypertensive
      drugs as covariates, the highest LVMI was found to be independently associated
      with a two-fold higher likelihood of having dementia. The association persisted
      significant even after adjustment for arterial stiffness. CONCLUSION: In elderly
      subjects, LVMI is associated with a progressive cognitive decline. This
      association is independent of BP levels and/or large artery stiffness.

PMID- 19406863
TI  - Guidelines for the physiotherapy management of the adult, medical, spontaneously
      breathing patient.

PMID- 19406865
TI  - Heritability of left ventricular and papillary muscle heart size: a twin study
      with cardiac magnetic resonance imaging.
AB  - AIMS: Earlier studies in monozygotic (MZ) and dizygotic (DZ) twins showed genetic
      variance on echocardiographically determined heart size. However, cardiovascular
      magnetic resonance (CMR) is more precise and reproducible. We performed a twin
      study relying on CMR, focusing on left ventricular (LV) mass and papillary
      muscle, since there are no genetic reports on this structure. METHODS AND
      RESULTS: We measured left heart dimensions of 25 healthy twin pairs with a 1.5T
      MR scanner, analysed with the mass, Medis Software. We performed heritability
      analysis and tests for genetic influences shared between cardiac structures. We
      found that CMR-based heritability estimates (h(2) = 84%) substantially exceeded
      estimates based on echocardiography. We also found significant genetic influence
      on papillary muscle mass (h(2) = 82%). Bivariate analysis of papillary and LV
      muscle mass revealed significant genetic influences shared by both phenotypes
      (genetic correlation 0.59) and suggested an additional genetic component specific
      to papillary muscle. We observed correlations between body mass index, surface
      area, and systolic blood pressure with cardiac dimensions, even in this small
      study. Environmental influences were relevant as well, indicating reciprocal
      influences on papillary vs. LV muscle mass. CONCLUSION: Cardiovascular magnetic
      resonance, even with few subjects, allows a genetic assessment of cardiac
      structures that cannot be attained with echocardiography. Hitherto fore
      unappreciated relationships can be uncovered by this method.

PMID- 19406866
TI  - Exercise haemodynamic variables rather than ventilatory efficiency indexes
      contribute to risk assessment in chronic heart failure patients treated with
      carvedilol.
AB  - AIMS: To evaluate the prognostic significance of traditional cardiopulmonary
      exercise testing (CPET) parameters in chronic heart failure (CHF) patients
      treated with beta-blockers. METHODS AND RESULTS: A total of 631 CHF patients were
      followed for cardiovascular death over 3.8 +/- 1.4 years; among them 79 (13%)
      died. All prognostic CPET parameters were related to outcome at univariate
      analysis, with haemodynamic-derived parameters [peak systolic blood pressure
      (SBP), peak circulatory power (CP) = peak oxygen consumption (pVO2) x peak SBP]
      and exertional oscillatory ventilation (EOV) reaching the highest chi2 (46.5,
      40.9, and 22.6, respectively, all with P < 0.0001). Exertional oscillatory
      ventilation, although associated with high mortality rate (43 vs. 11%, P <
      0.001), was detected in 42 (7%) patients. In non-EOV, again both peak SBP and
      peak CP reached the highest chi2 (30.6, and 21.6, respectively, all with P <
      0.0001). Regarding CPET parameters, at multivariable analysis, peak SBP was the
      strongest risk index both in total and non-EOV populations, with 11% risk
      reduction every 5 mmHg increase. CONCLUSION: All traditional CPET risk parameters
      were informative in beta-blockers CHF patients, but peak SBP, peak CP, and EOV
      were the most predictive. In this low-risk population, EOV, although
      underrepresented, considerably enhanced risk stratification, although other
      ventilatory efficiency indexes provided less impressive predictive content. In
      large majority of non-EOV patients, peak SBP improved risk evaluation beyond
      other CPET parameters.

PMID- 19406867
TI  - A frozen heart.

PMID- 19406868
TI  - MAHOROBA, first-in-man study: 6-month results of a biodegradable polymer
      sustained release tacrolimus-eluting stent in de novo coronary stenoses.
AB  - AIMS: To report the 4-month angiographic and 6-month clinical follow-up in first
      in-man study using the tacrolimus-eluting bioabsorbable polymer-coated cobalt
      chromium MAHOROBA stent. METHODS AND RESULTS: A total of 47 patients with either
      stable angina or unstable angina, or silent myocardial ischaemia, based on a de
      novo coronary stenosis that could be covered by a single 18 mm stent in a native
      coronary artery with a diameter between 3.0 and 3.5 mm were enrolled at three
      sites. The primary endpoint was in-stent late loss at 4 months. The secondary
      endpoints include %volume obstruction of the stents assessed by intravascular
      ultrasound (IVUS) at 4 months and major adverse cardiac events (MACE) at 6
      months. Forty-seven patients were enrolled. Procedural success was achieved in
      97.9%. At 4-month follow-up, in-stent late loss was 0.99 +/- 0.46 mm, whereas in
      stent %volume obstruction in IVUS was 34.8 +/- 15.8%. At 6 months, there were no
      deaths, but 2 patients suffered from a myocardial infarction and 11 patients
      required ischaemia-driven repeat revascularization. The composite MACE rate was
      23.4%. CONCLUSION: This tacrolimus-eluting stent failed to prevent neointimal
      hyperplasia, despite the theoretical advantages of the tacrolimus, which has less
      inhibitory effects on endothelial cells than smooth muscle cells.

PMID- 19406869
TI  - Myocardial bridging, a frequent component of the hypertrophic cardiomyopathy
      phenotype, lacks systematic association with sudden cardiac death.
AB  - AIMS: The clinical significance attributable to myocardial bridging of left
      anterior descending coronary artery in hypertrophic cardiomyopathy (HCM) remains
      controversial. METHODS AND RESULTS: Prevalence and depth of coronary artery
      bridges (CBs) were assessed in 255 hearts, including 115 with HCM (median age 29,
      range 5-90; 75% male), and 140 controls. Coronary artery bridges were more common
      in HCM (47/115; 41%) than in patients who died of a variety of non-HCM-related
      causes (21/100; 21%; P = 0.002), or in patients with congenital aortic stenosis
      and left ventricular (LV) hypertrophy (5/40; 12%; P = 0.001). Among the HCM
      hearts, CBs were present in 33 of 77 patients (43%) with sudden death, in 10 of
      27 (37%) with heart failure death (or heart transplantation), and in 4 of 11
      (36%) with other modes of death (P = 0.826). Deeply embedded CBs (> or =2 mm)
      occurred with similar frequency in HCM patients with sudden (21 of 77; 27%) or
      heart failure death (5 of 27; 13%; P = 0.191). In sudden death patients, the
      presence of CB was unrelated to gender (33% in women and 45% in men, P = 0.406)
      and age (41% <18 years vs. 44% > or =18 years; P = 0.827). CONCLUSION: In this
      morphological analysis of more than 250 hearts, CBs are a frequent component of
      phenotypically expressed HCM, and more common than in other disorders with or
      without LV hypertrophy. Although no systematic association with HCM-related
      sudden death is evident, our findings do not exclude the possibility that CB
      could contribute to increased risk in some individual patients, potentially
      impacting management decision-making on a case-by-case basis.

PMID- 19406870
TI  - Troponin is superior to electrocardiogram and creatinine kinase MB for predicting
      clinically significant myocardial injury after coronary artery bypass grafting.
AB  - AIMS: Cardiac biomarkers are routinely elevated after uncomplicated cardiac
      surgery to levels considered diagnostic of myocardial infarction in ambulatory
      populations. We investigated the diagnostic power of electrocardiogram (ECG) and
      cardiac biomarker criteria to predict clinically relevant myocardial injury using
      benchmarks of mortality and increased hospital length of stay (HLOS) in patients
      undergoing coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS:
      Perioperative ECGs, creatinine kinase MB fraction, and cardiac troponin I (cTnI)
      were assessed in 545 primary CABG patients. None of the ECG criteria for
      myocardial injury predicted mortality or HLOS. However, post-operative day (POD)
      1 cTnI levels independently predicted 5-year mortality (hazard ratio = 1.42; 95%
      CI 1.14-1.76 for each 10 microg/L increase; P = 0.009), while adjusting for
      baseline demographic characteristics and perioperative risk factors. Moreover,
      cTnI was the only biomarker that significantly improved the prediction of 5-year
      mortality estimated by the logistic Euroscore (P = 0.02). Furthermore, the
      predictive value of cTnI for 5-year mortality was replicated in a separately
      collected cohort of 1031 CABG patients using cardiac troponin T. CONCLUSION:
      Electrocardiogram diagnosis of post-operative myocardial injury after CABG does
      not independently predict an increased risk of 5-year mortality or HLOS.
      Conversely, cTnI is independently associated with an increased risk of mortality
      and prolonged HLOS.

PMID- 19406871
TI  - Effects of perindopril on cardiac remodelling and prognostic value of pre
      discharge quantitative echocardiographic parameters in elderly patients after
      acute myocardial infarction: the PREAMI echo sub-study.
AB  - AIMS: To determine (i) the effect of perindopril on several geometric and
      functional parameters of the left and right ventricles assessed by
      echocardiography in the unique Perindopril and Remodelling in Elderly with Acute
      Myocardial Infarction (PREAMI) population of post-acute myocardial infarction
      (AMI) elderly patients with preserved left ventricular (LV) function; and (ii)
      the prognostic predictors at pre-discharge derived from echo-Doppler measurements
      in the same population. METHODS AND RESULTS: PREAMI included 1252 post-AMI
      patients (age 73 +/- 6 years, LV ejection fraction 59.1 +/- 7.7%) receiving
      optimal therapy after AMI, randomized to perindopril 8 mg/day (n = 631) or
      placebo (n = 621); n = 896 had complete echo-Doppler data. Outcome measures were
      clinical [death, heart failure (HF)] and standard echo-Doppler parameters. Pre
      discharge LV end-diastolic volume (LVEDV) was similar: 81.1 +/- 23.1
      (perindopril) and 79.6 +/- 22.7 mL (placebo). At 6 months and 1 year, LVEDV
      remained unchanged with perindopril (81.2 +/- 24.4 and 81.8 +/- 26.8 mL,
      respectively), but increased with placebo (83.0 +/- 25.3 and 83.6 +/- 25.7 mL,
      respectively, both P < 0.001 vs. baseline). Perindopril reduced cardiac
      sphericity vs. placebo (P = 0.015 at 6 months; P = 0.020 at 1 year).
      Classification regression tree analysis showed treatment as the most important
      predictor of remodelling. Multiple pre-discharge echocardiographic variables
      predicted the death/HF endpoint, independently of treatment (P < or = 0.05).
      CONCLUSION: Remodelling occurs in post-AMI in elderly patients with normal LV
      function. Echo-Doppler variables at baseline have prognostic implications.
      Treatment with perindopril reduces progressive LV remodelling that can occur even
      in the case of small infarct size.

PMID- 19406872
TI  - BAY 58-2667, a nitric oxide-independent guanylyl cyclase activator,
      pharmacologically post-conditions rabbit and rat hearts.
AB  - AIMS: BAY 58-2667 (BAY-58) directly activates soluble guanylyl cyclase without
      tolerance in a nitric oxide (NO)-independent manner, and its haemodynamic effect
      is similar to that of nitroglycerin. We tested whether BAY-58 could make both
      rabbit and rat hearts resistant to infarction when given at the end of an
      ischaemic insult. METHODS AND RESULTS: All hearts were exposed to 30 min regional
      ischaemia followed by 120-(isolated hearts) or 180-(in situ hearts) min
      reperfusion. BAY-58 (1-50 nM) infused for 60 min starting 5 min before
      reperfusion significantly reduced infarction from 33.0 +/- 3.2% in control
      isolated rabbit hearts to 9.5-12.7% (P < 0.05). In a more clinically relevant in
      situ rabbit model, infarct size was similarly reduced with a loading dose of 53.6
      microg/kg followed by a 60 min infusion of 1.25 microg/kg/min (41.1 +/- 3.1%
      infarction in control hearts to 16.0 +/- 4.4% in treated hearts, P < 0.05). BAY
      58 similarly decreased infarction in the isolated rat heart, and protection was
      abolished by co-treatment with a protein kinase G (PKG) antagonist, or a
      mitochondrial K(ATP) channel antagonist. Conversely, N(omega)-nitro-L-arginine
      methyl-ester-hydrochloride, a NO-synthase inhibitor, failed to block BAY-58's
      ability to decrease infarction, consistent with the latter's putative NO
      independent activation of PKG. Finally, BAY-58 increased myocardial cGMP content
      in reperfused hearts while cAMP was unchanged. CONCLUSION: When applied at
      reperfusion, BAY-58 is an effective cardioprotective agent with a mechanism
      similar to that of ischaemic pre-conditioning and, hence, should be a candidate
      for treatment of acute myocardial infarction in man.

PMID- 19406874
TI  - Potential chemosignals associated with male identity in the amphisbaenian Blanus
      cinereus.
AB  - Pheromone-based chemosensory sex discrimination occurs in many reptiles, but the
      specific chemosignals responsible for this discrimination have been rarely
      identified. Chemoreception is especially important for amphisbaenians, a group of
      fossorial, almost blind, reptiles. We analyzed the role of semiochemicals
      produced by precloacal glands in intraspecific communication and chemosensory sex
      recognition of the amphisbaenian Blanus cinereus. We expected that sexual
      discrimination in amphisbaenians would be based on those chemicals that show
      intersexual differences in precloacal secretions, with squalene being the
      chemical that shows the greatest difference in relative abundance between sexes.
      Tongue-flick assays and behavioral responses to the scent of conspecifics
      confirmed that amphisbaenians are capable of detecting and discriminating between
      scent of conspecific males and females by using chemosensory cues alone.
      Differential responses of amphisbaenians to chemical compounds that are naturally
      found in precloacal secretions indicated that males can readily discriminate
      between different chemicals. Squalene, in particular, elicited in male
      amphisbaenians' chemosensory and aggressive responses that were similar to those
      elicited by precloacal secretions. This result suggests that squalene alone
      allows male discrimination by male amphisbaenians. Furthermore, squalene might
      also signal dominance status or aggressiveness of a male amphisbaenian because
      higher concentrations of squalene elicited higher levels of aggression by males.

PMID- 19406873
TI  - Olfactory cilia: linking sensory cilia function and human disease.
AB  - The olfactory system gives us an awareness of our immediate environment by
      allowing us to detect airborne stimuli. The components necessary for detection of
      these odorants are compartmentalized in the cilia of olfactory sensory neurons.
      Cilia are microtubule-based organelles, which can be found projecting from the
      surface of almost any mammalian cell, and are critical for proper olfactory
      function. Mislocalization of ciliary proteins and/or the loss of cilia cause
      impaired olfactory function, which is now recognized as a clinical manifestation
      of a broad class of human diseases, termed ciliopathies. Future work
      investigating the mechanisms of olfactory cilia function will provide us
      important new information regarding the pathogenesis of human sensory perception
      diseases.

PMID- 19406875
TI  - Checking your SOCCs and feet: the molecular mechanisms of Ca2+ entry in skeletal
      muscle.
AB  - It has long been known that skeletal muscle contraction persists in the absence
      of extracellular Ca(2+). Nevertheless, recent evidence indicates that multiple
      distinct Ca(2+) entry pathways exist in skeletal muscle: one active at negative
      potentials that requires store depletion (store-operated calcium entry or SOCE)
      and a second that is independent of store depletion and is activated by
      depolarization (excitation-coupled calcium entry or ECCE). This review highlights
      recent findings regarding the molecular identity, subcellular localization, and
      inter-relationship between SOCE and ECCE in skeletal muscle. The respective roles
      of ryanodine receptors (RyRs), dihydropyridine receptors (DHPRs), inositol-1,4,5
      trisphosphate receptors (IP(3)Rs), canonical transient receptor potential
      channels (TRPCs), STIM1 Ca(2+) sensor proteins, and Orai1 Ca(2+) permeable
      channels in mediating SOCE and ECCE in skeletal muscle are discussed. Differences
      between SOCE and ECCE in skeletal muscle with Ca(2+) entry mechanisms in non
      excitable cells are also reviewed. Finally, potential physiological roles for
      SOCE and ECCE in skeletal muscle development and function, as well as other
      currently unanswered questions and controversies in the field are also
      considered.

PMID- 19406876
TI  - Co-regulation of ocular dominance plasticity and NMDA receptor subunit expression
      in glutamic acid decarboxylase-65 knock-out mice.
AB  - Experience can shape cortical circuits, especially during critical periods for
      plasticity. In visual cortex, imbalance of activity from the two eyes during the
      critical period shifts ocular dominance (OD) towards the more active eye.
      Inhibitory circuits are crucial in this process: OD plasticity is absent in
      GAD65KO mice that show diminished inhibition. This defect can be rescued by
      application of benzodiazepines, which increase GABAergic signalling. However, it
      is unknown how such changes in inhibition might disrupt and then restore OD
      plasticity. Since NMDA dependent synaptic plasticity mechanisms are also known to
      contribute to OD plasticity, we investigated whether NMDA receptor levels and
      function are also altered in GAD65KO. There are reduced NR2A levels and slower
      NMDA currents in visual cortex of GAD65KO mice. Application of benzodiazepines,
      which rescues OD plasticity, also increases NR2A levels. Thus it appears as if OD
      plasticity can be restored by adding a critical amount of excitatory transmission
      through NR2A-containing NMDA receptors. Together, these observations can unify
      competing ideas of how OD plasticity is regulated: changes in either inhibition
      or excitation would engage homeostatic mechanisms that converge to regulate NMDA
      receptors, thereby enabling plasticity mechanisms and also ensuring circuit
      stability.

PMID- 19406879
TI  - Swine flu.

PMID- 19406877
TI  - The evolutionarily conserved residue A653 plays a key role in HERG channel
      closing.
AB  - Human ether-a-go-go-related gene (HERG) encodes the rapid, outwardly rectifying
      K(+) current I(Kr) that is critical for repolarization of the cardiac action
      potential. Congenital HERG mutations or unintended pharmaceutical block of I(Kr)
      can lead to life-threatening arrhythmias. Here, we assess the functional role of
      the alanine at position 653 (HERG-A653) that is highly conserved among
      evolutionarily divergent K(+) channels. HERG-A653 is close to the 'glycine hinge'
      implicated in K(+) channel opening, and is flanked by tyrosine 652 and
      phenylalanine 656, which contribute to the drug binding site. We substituted an
      array of seven (I, C, S, G, Y, V and T) amino acids at position 653 and expressed
      individual variants in heterologous systems to assess changes in gating and drug
      binding. Substitution of A653 resulted in negative shifts of the V(1/2) of
      activation ranging from -23.6 (A653S) to -62.5 (A653V) compared to -11.2 mV for
      wild-type (WT). Deactivation was also drastically altered: channels with A653I/C
      substitutions exhibited delayed deactivation in response to test potentials above
      the activation threshold, while A653S/G/Y/V/T failed to deactivate under those
      conditions and required hyperpolarization and prolonged holding potentials at 
      130 mV. While A653S/G/T/Y variants showed decreased sensitivity to the I(Kr)
      inhibitor dofetilide, these changes could not be correlated with defects in
      channel closure. Homology modelling suggests that in the closed state, A653 forms
      tight contacts with several residues from the neighbouring subunit in the
      tetramer, playing a key role in S6 helix packing at the narrowest part of the
      vestibule. Our study suggests that A653 plays an important functional role in the
      outwardly rectifying gating behaviour of HERG, supporting channel closure at
      membrane potentials negative to the channel activation threshold.

PMID- 19406881
TI  - WHO raises flu pandemic alert to level 5.

PMID- 19406878
TI  - TRPV1 channels control synaptic plasticity in the developing superior colliculus.
AB  - Long-term depression (LTD) in the rodent superior colliculus (SC) is regarded as
      a model of synaptic refinement because it can be induced during development but
      not in adults. We investigated the role of transient receptor potential vanilloid
      type-1 (TRPV1) channels in this type of synaptic plasticity. Experiments were
      carried out in pigmented mice aged between postnatal day 8 (P8) and 42 (P42) and
      in adult mice. Retinal axons to the SC were labelled by injection of cholera
      toxin-beta (CTbeta) into the eye. Immunohistochemical staining for CTbeta, TRPV1
      and markers of glutamatergic and GABAergic cells and fibres (VGLUT1 and VGAT or
      GAD65, respectively) was performed by using multiple immunofluorescence. This
      showed that both glutamatergic retinal afferents to, and some GABAergic neurones
      in, the superficial SC are TRPV1 positive in juvenile but not adult mice. Field
      potential recordings were made from the superficial grey layer in parasagittal SC
      slices, and LTD (76 +/- 8% of control responses) was induced with a 50 Hz, 20 s
      tetanus. Activation of TRPV1 with resiniferatoxin also reduced field potential
      amplitude to 84 +/- 8% of control values. Blockade of TRPV1 with the selective
      antagonist 5'-iodo-resiniferatoxin prevented the induction of LTD (98 +/- 4% of
      control values), but did not cause its reversal if LTD was already established. N
      acylphosphatidylethanolamine-specific phospholipase D and 12-lipoxygenase, two
      proposed endovanilloid biosynthesizing enzymes, were co-expressed with TRPV1 in
      the SC at P14 and P28. These results suggest that TRPV1 modulates
      retinocollicular responses in the developing SC and is activated during tetanic
      stimulation by endovanilloid ligands to participate in the induction of LTD.

PMID- 19406882
TI  - A new answer to an old question: does ageing modify baroreflex control of
      vascular sympathetic outflow in humans?

PMID- 19406883
TI  - O2 sensing in chromaffin cells: new duties for T-type channels.

PMID- 19406884
TI  - Mechanisms of neocortical development.

PMID- 19406885
TI  - Fetal cerebral blood flow, electrocorticographic activity, and oxygenation:
      responses to acute hypoxia.
AB  - Arterial blood gases are critical in regulation of cerebral blood flow (CBF) and
      cerebral metabolic rate for O(2) (CMRO(2)). However, the relation of these
      variables to cortical tissue (t ), and electrocorticographic (ECoG) activity
      (high voltage low frequency, HVLF, versus low voltage high frequency, LVHF), are
      not well defined. In the fetus, we tested the hypothesis that ECoG pattern is
      associated closely with cerebral oxygenation. In fetal sheep (n = 8) with laser
      Doppler flowmeter, fluorescent O(2) probe and ECoG electrodes, we measured laser
      Doppler CBF (LD-CBF), tP(O2), ECoG and spectral edge frequency-90 (SEF(90)) in
      response to 40 min isocapnic hypoxia. In the normoxic fetus, LD-CBF and CMRO(2)
      correlated highly with ECoG state. With a shift from HVLF to LVHF, tP(O2)
      decreased followed by increased LD-CBF (18%) and CMRO(2) (13%). With acute
      hypoxia (P(aO2)= 12 +/- 1 Torr), tp(O2) decreased toapproximately 3 Torr, LD-CBF
      increased 48 +/- 10%, ECoG shifted to chiefly the HVLF state, SEF(90) decreased
      approximately 15%, and CMRO(2) decreased approximately 20% (P < 0.05 for each).
      For the normoxic fetus, CBF was closely related to ECoG state, but this
      association was less evident during acute hypoxia. We speculate that, in the
      otherwise stressed fetus, acute hypoxia may further compromise cerebral
      oxygenation.

PMID- 19406886
TI  - Long term monitoring in patients receiving treatment to lower blood pressure:
      analysis of data from placebo controlled randomised controlled trial.
AB  - OBJECTIVE: To determine the value of monitoring blood pressure by quantifying the
      probability that observed changes in blood pressure reflect true changes. DESIGN:
      Analysis of blood pressure measurements of patients in the perindopril protection
      against recurrent stroke study (PROGRESS). SETTING: Randomised placebo controlled
      trial carried out in 172 centres in Asia, Australasia, and Europe. PARTICIPANTS:
      1709 patients with history of stroke or transient ischaemic attack randomised to
      fixed doses of perindopril and indapamide. Measurements Mean of two blood
      pressure measurements in patients receiving treatment recorded to the nearest 2
      mm Hg with a standard mercury sphygmomanometer at baseline and then at three
      months, six months, nine months, and 15 months and then every six months to 33
      months. RESULTS: There was no change in the mean blood pressure of the cohort
      during the 33 month follow-up. Six months after blood pressure was stabilised on
      treatment, if systolic blood pressure was measured as having increased by >10 mm
      Hg, six of those measurements would be false positives for every true increase of
      >or=10 mm Hg. The corresponding value for an increase of 20 mm Hg was over 200.
      Values for 5 mm Hg and 10 mm Hg increases in diastolic blood pressure were 3.5
      and 39, respectively. The likelihood that observed increases in blood pressure
      reflected true increases rose with the time between measurements such that the
      ratio of true positives to false positives reached parity at 21 months.
      CONCLUSIONS: Usual clinical approaches to the monitoring of patients taking drugs
      to lower blood pressure have a low probability of yielding reliable information
      about true changes in blood pressure. Evidence based guidelines for monitoring
      treatment response are urgently required to guide clinical practice. Trial
      registration Australia and New Zealand Clinical Trial Registry.

PMID- 19406888
TI  - Delivering quality and value in heart failure.

PMID- 19406889
TI  - The death of DNR.

PMID- 19406887
TI  - Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1
      among injecting drug users: prospective cohort study.
AB  - OBJECTIVE: To examine the relation between plasma HIV-1 RNA concentrations in the
      community and HIV incidence among injecting drug users. DESIGN: Prospective
      cohort study. SETTING: Inner city community in Vancouver, Canada. PARTICIPANTS:
      Injecting drug users, with and without HIV, followed up every six months between
      1 May 1996 and 30 June 2007. MAIN OUTCOME MEASURES: Estimated community plasma
      HIV-1 RNA in the six months before each HIV negative participant's follow-up
      visit. Associated HIV incidence. RESULTS: Among 622 injecting drug users with
      HIV, 12 435 measurements of plasma HIV-1 RNA were obtained. Among 1429 injecting
      drug users without HIV, there were 155 HIV seroconversions, resulting in an
      incidence density of 2.49 (95% confidence interval 2.09 to 2.88) per 100 person
      years. In a Cox model that adjusted for unsafe sexual behaviours and sharing used
      syringes, the estimated community plasma HIV-1 RNA concentration remained
      independently associated with the time to HIV seroconversion (hazard ratio 3.32
      (1.82 to 6.08, P<0.001), per log(10) increase). When the follow-up period was
      limited to observations after 1 January 1988 (when the median plasma HIV RNA
      concentration was <20 000 copies/ml), the median viral load was no longer
      statistically associated with HIV incidence (1.70 (0.79 to 3.67, P=0.175), per
      log(10) increase). CONCLUSIONS: A longitudinal measure of community plasma HIV-1
      RNA concentration was correlated with the community HIV incidence rate and
      predicted HIV incidence independent of unsafe sexual behaviours and sharing used
      syringes. If these findings are confirmed, they could help to inform both HIV
      prevention and treatment interventions.

PMID- 19406890
TI  - Investing in midwives is essential to reduce maternal mortality in fragile
      states.

PMID- 19406891
TI  - Independent sector treatment centres: learning from a Scottish case study.

PMID- 19406892
TI  - Contrasting ethical policies of physicians and psychologists concerning
      interrogation of detainees.

PMID- 19406893
TI  - Intercistronic heterogeneity of the 16S-23S rRNA spacer region among Pseudomonas
      strains isolated from subterranean seeds of hog peanut (Amphicarpa bracteata).
AB  - Intercistronic heterogeneity of the 16S-23S rRNA internal transcribed spacer
      regions (ITS1) was investigated in 29 strains of fluorescent pseudomonads
      isolated from subterranean seeds of Amphicarpa bracteata (hog peanut). PCR
      amplification of the ITS1 region generated one or two products from the strains.
      Sequence analysis of the amplified fragments revealed an ITS1 fragment of about
      517 bp that contained genes for tRNA(Ile) and tRNA(Ala) in all 29 strains; an
      additional smaller ITS1 of 279 bp without tRNA features was detected in 15 of the
      strains. The length difference appeared to be due to deletions of several
      nucleotide blocks between the 70 bp and 359 bp positions of the alignment. The
      end of the deletions in the variant ITS1 type coincided with the start of
      antiterminator box A, which is homologous to box A of other bacteria.
      Phylogenetic analyses using the neighbour-joining algorithm revealed two major
      phylogenetic clusters, one for each of the ITS1 types. Using a single specific
      primer set and the DNA-intercalating dye SYBR Green I for real-time PCR and
      melting-curve analysis produced highly informative curves with one or two
      recognizable melting peaks that readily distinguished between the two ITS1 types
      in pure cultures. The assay was used to confirm the presence of the variant ITS1
      type in the Pseudomonas community in total DNA from root-zone soil and seed coats
      of hog peanut. Heterogeneity of the ITS1 region between species has potential for
      studying molecular systematics and population genetics of the genus Pseudomonas,
      but the presence of non-identical rRNA operons within a genome may pose problems.

PMID- 19406894
TI  - Resistance to peroxynitrite in Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae encodes a number of important genes that aid in survival
      during times of oxidative stress. The same immune cells capable of oxygen
      dependent killing mechanisms also have the capacity to generate reactive nitrogen
      species (RNS) that may function antimicrobially. F62 and eight additional
      gonococcal strains displayed a high level of resistance to peroxynitrite, while
      Neisseria meningitidis and Escherichia coli showed a four- to seven-log and a
      four-log decrease in viability, respectively. Mutation of gonococcal orthologues
      that are known or suspected to be involved in RNS defence in other bacteria
      (ahpC, dnrN and msrA) resulted in no loss of viability, suggesting that N.
      gonorrhoeae has a novel mechanism of resistance to peroxynitrite. Whole-cell
      extracts of F62 prevented the oxidation of dihydrorhodamine, and decomposition of
      peroxynitrite was not dependent on ahpC, dnrN or msrA. F62 grown in co-culture
      with E. coli strain DH10B was shown to protect E. coli viability 10-fold. Also,
      peroxynitrite treatment of F62 did not result in accumulation of nitrated
      proteins, suggesting that an active peroxynitrite reductase is responsible for
      peroxynitrite decomposition rather than a protein sink for amino acid
      modification.

PMID- 19406896
TI  - Intracellular 2-keto-3-deoxy-6-phosphogluconate is the signal for carbon
      catabolite repression of phenylacetic acid metabolism in Pseudomonas putida
      KT2440.
AB  - The growth pattern of Pseudomonas putida KT2440 in the presence of glucose and
      phenylacetic acid (PAA), where the sugar is used in preference to the aromatic
      compound, suggests that there is carbon catabolite repression (CCR) of PAA
      metabolism by glucose or gluconate. Furthermore, CCR is regulated at the
      transcriptional level. However, this CCR phenomenon does not occur in PAA-amended
      minimal medium containing fructose, pyruvate or succinate. We previously
      identified 2-keto-3-deoxy-6-phosphogluconate (KDPG) as an inducer of glucose
      metabolism, and this has led to this investigation into the role of KDPG as a
      signal compound for CCR. Two mutant strains, the edd mutant (non-KDPG producer)
      and the eda mutant (KDPG overproducer), grew in the presence of PAA but not in
      the presence of glucose. The edd mutant utilized PAA even in the presence of
      glucose, indicating that CCR had been abolished. This observation has additional
      support from the finding that there is high phenylacetyl-CoA ligase activity in
      the edd mutant, even in the presence of glucose+PAA, but not in wild-type cells
      under the same conditions. Unlike the edd mutant, the eda mutant did not grow in
      the presence of glucose+PAA. Interestingly, there was no uptake and/or metabolism
      of PAA in the eda mutant cells under the same conditions. Targeted disruption of
      PaaX, a repressor of the PAA operon, had no effect on CCR of PAA metabolism in
      the presence of glucose, suggesting that there is another transcriptional
      repression system associated with the KDPG signal. This is the first study to
      demonstrate that KDPG is the true CCR signal of PAA metabolism in P. putida
      KT2440.

PMID- 19406897
TI  - Identification of novel Ralstonia solanacearum type III effector proteins through
      translocation analysis of hrpB-regulated gene products.
AB  - The Hrp type III secretion system (TTSS) is essential for the pathogenicity of
      Ralstonia solanacearum on host plants. Hrp TTSS is a specialized secretion system
      that injects virulence proteins, the so-called type III effector proteins, into
      plant cells. In R. solanacearum, the expression of Hrp TTSS-related genes is
      regulated by an AraC-type transcriptional activator, HrpB. We have identified 30
      hrpB-regulated hpx (hrpB-dependent expression) genes and three well-known hrpB
      regulated genes, popA, popB and popC, as candidate effector genes in R.
      solanacearum strain RS1000. In this study, we newly cloned 11 additional
      candidate effector genes that share homology with known hpx genes from R.
      solanacearum RS1000. Using a Cya reporter system, we investigated the
      translocation of these 44 gene products into plant cells via the Hrp TTSS and
      identified 34 effector proteins. These include three effector families composed
      of more than four members, namely the Hpx4, Hpx30 and GALA families. The Hpx30
      family effectors are 2200-2500 aa in size and appear to be the largest class of
      effector proteins among animal- and plant-pathogenic bacteria. Members of this
      family contain 12-18 tandem repeats of a novel 42 aa motif, designated SKWP
      repeats.

PMID- 19406895
TI  - Identification of genes required for Pseudomonas aeruginosa carnitine catabolism.
AB  - Carnitine is a quaternary amine compound prevalent in animal tissues, and a
      potential carbon, nitrogen and energy source for pathogens during infection.
      Characterization of activities in Pseudomonas aeruginosa cell lysates has
      previously shown that carnitine is converted to 3-dehydrocarnitine (3-dhc) which
      is in turn metabolized to glycine betaine (GB), an intermediate metabolite in the
      catabolism of carnitine to glycine. However, the identities of the enzymes
      required for carnitine catabolism were not known. We used a genetic screen of the
      P. aeruginosa PA14 transposon mutant library to identify genes required for
      growth on carnitine. We identified two genomic regions and their adjacent
      transcriptional regulators that are required for carnitine catabolism. The PA5388
      PA5384 region contains the predicted P. aeruginosa carnitine dehydrogenase
      homologue along with other genes required for growth on carnitine. The second
      region identified, PA1999-PA2000, encodes the alpha and beta subunits of a
      predicted 3-ketoacid CoA-transferase, an enzymic activity hypothesized to be
      involved in the first step of deacetylation of 3-dhc. Furthermore, we confirmed
      that an intact GB catabolic pathway is required for growth on carnitine. The
      PA5389 and PA1998 transcription factors are required for growth on carnitine.
      PA5389 is required for induction of the PA5388-PA5384 transcripts in response to
      carnitine, and the PA1999-PA2000 transcripts are induced in a PA1998-dependent
      manner and induction appears to depend on a carnitine catabolite, possibly 3-dhc.
      These results provide important insight into elements required for carnitine
      catabolism in P. aeruginosa and probably in other bacteria.

PMID- 19406898
TI  - The DNA static curvature has a role in the regulation of the ompS1 porin gene in
      Salmonella enterica serovar Typhi.
AB  - The DNA static curvature has been described to play a key role as a regulatory
      element in the transcription process of several bacterial genes. Here, the role
      of DNA curvature in the expression of the ompS1 porin gene in Salmonella enterica
      serovar Typhi is described. The web server mutacurve was used to predict
      mutations that diminished or restored the extent of DNA curvature in the 5'
      regulatory region of ompS1. Using these predictions, curvature was diminished by
      site-directed mutagenesis of only two residues, and curvature was restored by
      further mutagenesis of the same two residues. Lowering the extent of DNA
      curvature resulted in an increase in ompS1 expression and in the diminution of
      the affinity of the silencer proteins H-NS and StpA for the ompS1 5' regulatory
      region. These mutations were in a region shown not to contain the H-NS nucleation
      site, consistent with the notion that the effect on expression was due to changes
      in DNA structural topology.

PMID- 19406899
TI  - Actinomyces naeslundii in initial dental biofilm formation.
AB  - The combined use of confocal laser scanning microscopy (CLSM) and fluorescent in
      situ hybridization (FISH) offers new opportunities for analysis of the spatial
      relationships and temporal changes of specific members of the microbiota of
      intact dental biofilms. The purpose of this study was to analyse the patterns of
      colonization and population dynamics of Actinomyces naeslundii compared to
      streptococci and other bacteria during the initial 48 h of biofilm formation in
      the oral cavity. Biofilms developed on standardized glass slabs mounted in intra
      oral appliances worn by ten individuals for 6, 12, 24 and 48 h. The biofilms were
      subsequently labelled with probes against A. naeslundii (ACT476), streptococci
      (STR405) or all bacteria (EUB338), and were analysed by CLSM. Labelled bacteria
      were quantified by stereological tools. The results showed a notable increase in
      the number of streptococci and A. naeslundii over time, with a tendency towards a
      slower growth rate for A. naeslundii compared with streptococci. A. naeslundii
      was located mainly in the inner part of the multilayered biofilm, indicating that
      it is one of the species that attaches directly to the acquired pellicle. The
      participation of A. naeslundii in the initial stages of dental biofilm formation
      may have important ecological consequences.

PMID- 19406902
TI  - Enhancement of the recombinagenic and mutagenic activities of bleomycin in yeast
      by intercalation of acridine compounds into DNA.
AB  - Strain D7 of Saccharomyces cerevisiae was used to measure the induction by
      bleomycin (BLM) of mitotic recombination at the trp5 locus and point mutations at
      ilv1 in the presence and absence of acridine compounds. BLM is a potent mutagen
      and recombinagen in the D7 assay. The acridines vary, some being mutagenic or
      recombinagenic and others not. Combined treatments were used to distinguish
      whether a genetically inactive acridine has no effect on the genetic activity of
      BLM or modulates its action. When an acridine is itself genetically active,
      combined treatments were used to determine whether its effects are additive with
      those of BLM or whether there is interaction between the two compounds. Acridine
      compounds that share the ability to intercalate between the base pairs of DNA but
      differ in their mutagenic specificity owing to the presence of different
      substituent groups were analysed. Clear potentiation and synergistic interactions
      were detected in combined treatments with BLM and aminoacridines, nitroacridines
      or an acridine mustard. Potentiation and synergy were also observed in sequential
      exposures in which the yeast were grown in the presence of acridine compounds and
      then treated with BLM in the absence of free acridine. The results are consistent
      with an increase in BLM susceptibility conferred by acridine intercalation. It is
      likely that the intercalating agents increase the access of BLM to the minor
      groove of DNA, where it abstracts a hydrogen from the 4' position of deoxyribose,
      creating a free radical that is processed into strand breaks.

PMID- 19406901
TI  - Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and
      fluoropyrimidines in metastatic colorectal cancer: the BEAT study.
AB  - BACKGROUND: Bevacizumab significantly improves survival when added to
      chemotherapy for metastatic colorectal cancer (mCRC). The Bevacizumab Expanded
      Access Trial (BEAT) evaluated the safety and efficacy of bevacizumab plus first
      line chemotherapy in a general cohort of patients with mCRC. PATIENTS AND
      METHODS: Patients with unresectable mCRC received chemotherapy (physician's
      choice) plus bevacizumab [5 mg/kg every 2 weeks (5-fluorouracil regimens) or 7.5
      mg/kg every 3 weeks (capecitabine regimens)]. The primary end point was safety,
      including prospective data collection in patients receiving unanticipated surgery
      during the study. Secondary objectives were progression-free survival (PFS) and
      overall survival (OS). RESULTS: The final analysis comprised 1914 assessable
      patients (male 58%; median age 59 years). Chemotherapy included 5
      fluorouracil/leucovorin (5-FU/LV) + oxaliplatin (29%), irinotecan plus 5-FU/LV
      (26%), capecitabine plus oxaliplatin (18%) and monotherapy (16%). Serious/grade 3
      5 adverse events of interest for bevacizumab included bleeding (3%),
      gastrointestinal perforation (2%), arterial thromboembolism (1%), hypertension
      (5.3%), proteinuria (1%) and wound-healing complications (1%). Sixty-day
      mortality was 3%. Median PFS was 10.8 months [95% confidence interval (CI) 10.4
      11.3 months] and median OS reached 22.7 months (95% CI 21.7-23.8 months).
      CONCLUSIONS: The BEAT study shows that the efficacy and safety profile of
      bevacizumab in routine clinical practice is consistent with results observed in
      prospective randomised clinical trials and another large observational study in
      the United States (BRiTE study).

PMID- 19406904
TI  - Structural connectivity for visuospatial attention: significance of ventral
      pathways.
AB  - In the present study, we identified the most probable trajectories of point-to
      point segregated connections between functional attentional centers using a
      combination of functional magnetic resonance imaging and a novel diffusion tensor
      imaging-based algorithm for pathway extraction. Cortical regions activated by a
      visuospatial attention task were subsequently used as seeds for probabilistic
      fiber tracking in 26 healthy subjects. Combining probability maps of frontal and
      temporoparietal regions yielded a network that consisted of dorsal and ventral
      connections. The dorsal connections linked temporoparietal cortex with the
      frontal eye field and area 44 of the inferior frontal gyrus (IFG). Traveling
      along superior longitudinal and arcuate fascicles, these fibers are well
      described in relation to spatial attention. However, the ventral connections,
      which traveled in the white matter between insula (INS) cortex and putamen
      parallel to the sylvian fissure, were not previously described for visuospatial
      attention. Linking temporoparietal cortex with anterior INS and area 45 of IFG,
      these connections may provide an anatomical substrate for crossmodal cortical
      integration needed for stimulus perception and response in relation to current
      intention. The newly anatomically described integral network for visuospatial
      attention might improve the understanding of spatial attention deficits after
      white matter lesions.

PMID- 19406903
TI  - Functional heterogeneity of inferior parietal cortex during mathematical
      cognition assessed with cytoarchitectonic probability maps.
AB  - Although the inferior parietal cortex (IPC) has been consistently implicated in
      mathematical cognition, the functional roles of its subdivisions are poorly
      understood. We address this problem using probabilistic cytoarchitectonic maps of
      IPC subdivisions intraparietal sulcus (IPS), angular gyrus (AG), and
      supramarginal gyrus. We quantified IPC responses relative to task difficulty and
      individual differences in task proficiency during mental arithmetic (MA) tasks
      performed with Arabic (MA-A) and Roman (MA-R) numerals. The 2 tasks showed
      similar levels of activation in 3 distinct IPS areas, hIP1, hIP2, and hIP3,
      suggesting their obligatory role in MA. Both AG areas, PGa and PGp, were strongly
      deactivated in both tasks, with stronger deactivations in posterior area PGp.
      Compared with the more difficult MA-R task, the MA-A task showed greater
      responses in both AG areas, but this effect was driven by less deactivation in
      the MA-A task. AG deactivations showed prominent overlap with lateral parietal
      nodes of the default mode network, suggesting a nonspecific role in MA. In both
      tasks, greater bilateral AG deactivation was associated with poorer performance.
      Our findings suggest a close link between IPC structure and function and they
      provide new evidence for behaviorally salient functional heterogeneity within the
      IPC during mathematical cognition.

PMID- 19406905
TI  - Cortical connections of the macaque caudal ventrolateral prefrontal areas 45A and
      45B.
AB  - We have found that the 2 architectonic subdivisions of the prefrontal area 45,
      45A and 45B, display connectivity patterns that clearly distinguish them from one
      another and from their neighboring architectonic areas. Area 45A is primarily
      connected to the frontal areas 45B, 12l, caudal 12r, 12o, 10, rostrodorsal 46,
      9/8B, 44, 8/FEF (frontal eye field), and the SEF (supplementary eye field),
      temporal area IPa, and unique among all the studied areas, to the superior
      temporal polysensory (STP) area and auditory parabelt areas. Area 45B displayed
      much stronger frontal connections with the oculomotor areas 8/FEF, 8r, and the
      SEF than those of area 45A, primary connections with areas 12l, caudal 12r, 12o,
      and 8B, and unlike area 45A, with areas ventrorostral 46, rostral 12r, 12m, and
      13m. Temporal connections were all virtually confined to areas IPa, intermediate
      TEa/m, and TE. Additional labeling was found in lateral intraparietal area. Our
      data suggest that 45A and 45B are 2 distinct areas, possibly playing a
      differential role in nonspatial information processing: area 45A corresponds to
      the prefrontal sector for which a role in communication behavior and homology
      with the human area 45 was proposed, whereas area 45B is a distinct prearcuate
      area, possibly affiliated to the oculomotor frontal system.

PMID- 19406906
TI  - What motivates the adolescent? Brain regions mediating reward sensitivity across
      adolescence.
AB  - The relation between brain development across adolescence and adolescent risky
      behavior has attracted increasing interest in recent years. It has been proposed
      that adolescents are hypersensitive to reward because of an imbalance in the
      developmental pattern followed by the striatum and prefrontal cortex. To date, it
      is unclear if adolescents engage in risky behavior because they overestimate
      potential rewards or respond more to received rewards and whether these effects
      occur in the absence of decisions. In this study, we used a functional magnetic
      resonance imaging paradigm that allowed us to dissociate effects of the
      anticipation, receipt, and omission of reward in 10- to 12-year-old, 14- to 15
      year-old, and 18- to 23-year-old participants. We show that in anticipation of
      uncertain outcomes, the anterior insula is more active in adolescents compared
      with young adults and that the ventral striatum shows a reward-related peak in
      middle adolescence, whereas young adults show orbitofrontal cortex activation to
      omitted reward. These regions show distinct developmental trajectories. This
      study supports the hypothesis that adolescents are hypersensitive to reward and
      adds to the current literature in demonstrating that neural activation differs in
      adolescents even for small rewards in the absence of choice. These findings may
      have important implications for understanding adolescent risk-taking behavior.

PMID- 19406900
TI  - Genomic DNA microarray comparison of gene expression patterns in Paracoccidioides
      brasiliensis mycelia and yeasts in vitro.
AB  - Paracoccidioides brasiliensis is a thermally dimorphic fungus, and causes the
      most prevalent systemic mycosis in Latin America. Infection is initiated by
      inhalation of conidia or mycelial fragments by the host, followed by further
      differentiation into the yeast form. Information regarding gene expression by
      either form has rarely been addressed with respect to multiple time points of
      growth in culture. Here, we report on the construction of a genomic DNA
      microarray, covering approximately 25 % of the genome of the organism, and its
      utilization in identifying genes and gene expression patterns during growth in
      vitro. Cloned, amplified inserts from randomly sheared genomic DNA (gDNA) and
      known control genes were printed onto glass slides to generate a microarray of
      over 12,000 elements. To examine gene expression, mRNA was extracted and
      amplified from mycelial or yeast cultures grown in semi-defined medium for 5, 8
      and 14 days. Principal components analysis and hierarchical clustering indicated
      that yeast gene expression profiles differed greatly from those of mycelia,
      especially at earlier time points, and that mycelial gene expression changed less
      than gene expression in yeasts over time. Genes upregulated in yeasts were found
      to encode proteins shown to be involved in methionine/cysteine metabolism,
      respiratory and metabolic processes (of sugars, amino acids, proteins and
      lipids), transporters (small peptides, sugars, ions and toxins), regulatory
      proteins and transcription factors. Mycelial genes involved in processes such as
      cell division, protein catabolism, nucleotide biosynthesis and toxin and sugar
      transport showed differential expression. Sequenced clones were compared with
      Histoplasma capsulatum and Coccidioides posadasii genome sequences to assess
      potentially common pathways across species, such as sulfur and lipid metabolism,
      amino acid transporters, transcription factors and genes possibly related to
      virulence. We also analysed gene expression with time in culture and found that
      while transposable elements and components of respiratory pathways tended to
      increase in expression with time, genes encoding ribosomal structural proteins
      and protein catabolism tended to sharply decrease in expression over time,
      particularly in yeast. These findings expand our knowledge of the different
      morphological forms of P. brasiliensis during growth in culture.

PMID- 19406907
TI  - Commentary: Spatial clustering of HIV infection: providing clues for effective
      HIV prevention.

PMID- 19406908
TI  - Intra-articular clodronate for the treatment of knee osteoarthritis: dose ranging
      study vs hyaluronic acid.
AB  - OBJECTIVE: Bisphosphonates may have a chondroprotective effect in patients with
      knee OA (KOA), but the results of clinical trials with oral bisphosphonates have
      been contradictory. In this Phase 2 randomized, partially blind clinical trial,
      we tested the efficacy of IA clodronate vs HA in patients with primary KOA.
      METHODS: One hundred and fifty men or women aged 50-75 years suffering from KOA
      were randomized to one of five IA therapies: (i) clodronate 0.5 mg one IA
      injection/week for 4 weeks; (ii) clodronate 1 mg one IA injection/week for 4
      weeks; (iii) clodronate 2 mg one IA injection/week for 4 weeks; (iv) clodronate 1
      mg two IA injections/week for 2 weeks (clodronate 1 + 1 mg); and (v) HA 20 mg one
      IA injection/week for 4 weeks. RESULTS: Visual analogue scores (VASs) for
      different types of pain and the Lequesne index significantly improved in all
      treatment groups after the first injection and continued to improve even 2-4
      weeks after the last injection without significant difference among the groups. A
      significant (P = 0.03) linear trend for a dose-response (0.5-2 mg clodronate)
      relationship was found for active movement VAS pain. Both joint extension and
      mobility scores improved significantly at all time points in all treatment groups
      without statistical differences among them. CONCLUSIONS: This study indicates
      that IA clodronate provides symptomatic and functional improvements at least as
      good as those obtained with HA. Trial Registration. Osservatorio Nazionale sulla
      Sperimentazione Clinica dei Medicinali - Agenzia Italiana del Farmaco. Comitato
      Etico Azienda Ospedaliera Universitaria Senese number CLIO 22/02 http://oss-sper
      clin.agenziafarmaco.it.

PMID- 19406909
TI  - Quantitative determination of airborne respirable non-fibrous alpha-silicon
      carbide by x-ray powder diffractometry.
AB  - OBJECTIVES: The purpose of the present investigation was to establish a method
      for the determination of airborne respirable non-fibrous silicon carbide (SiC).
      The main application is within the industrial production of SiC. METHODS: Due to
      the complex airborne aerosol mixture of crystalline compounds in the SiC
      industry, X-ray powder diffractometry was selected as the most appropriate
      method. Without any international standard material for the respirable fraction
      of non-fibrous SiC, pure and suitable products from three SiC plants in Norway
      were selected. These products have a median particle diameter in the range 4.4
      5.1 mum. The method is based on thin sample technique, with the dust deposited on
      a polycarbonate filter. Absorption correction is done by standard procedures with
      the use of a silver filter, situated below the polycarbonate filter. RESULTS: The
      diffraction line used for quantitative determination was selected carefully. This
      was done to avoid interferences from quartz, cristobalite, and graphite, which
      all are airborne components present in the atmosphere during the industrial
      process. The instrumental limit of detection for the method is 12 microg.
      CONCLUSIONS: This method has been used to determine airborne non-fibrous SiC in a
      comprehensive ongoing project in the Norwegian SiC industry for further
      epidemiological studies. The method is fully applicable for compliance work.

PMID- 19406910
TI  - Methods for measuring performance of vehicle cab air cleaning systems against
      aerosols and vapours.
AB  - Vehicle cabs equipped with an effective air cleaning and pressurization system,
      fitted to agricultural and off-road machineries, isolate drivers from the
      polluted environment, in which they are likely to work. These cabs provide
      protection against particulate and gaseous pollutants generated by these types of
      work activities. Two laboratory methods have been applied to determining the
      performance characteristics of two cabs of different design, namely, optical
      counting-based measurement of a potassium chloride (KCl) aerosol and fluorescein
      aerosol-based tracing. Results of cab confinement efficiency measurements agreed
      closely for these two methods implemented in the study. Measurements showed that
      high confinement efficiencies can be achieved with cabs, which are properly
      designed in ventilation/cleaning/airtightness terms. We also noted the importance
      of filter mounting airtightness, in which the smallest defect is reflected by
      significant degradation in cab performance. Determination of clean airflow rate
      by monitoring the decrease in test aerosol concentration in the test chamber gave
      excellent results. This method could represent an attractive alternative to
      methods involving gas tracing or air velocity measurement at blowing inlets.

PMID- 19406911
TI  - Statins normalize vascular lysyl oxidase down-regulation induced by
      proatherogenic risk factors.
AB  - AIMS: Statins are lipid-lowering drugs widely used in the management of vascular
      diseases. Clinical and experimental evidence suggest that statins improve
      endothelial function by both cholesterol-lowering-dependent and -independent
      mechanisms. We have previously shown that endothelial dysfunction induced by risk
      factors and proinflammatory cytokines is associated with down-regulation of lysyl
      oxidase (LOX), a key enzyme modulating extracellular matrix maturation and
      vascular integrity. Our aim was to analyse whether statins could normalize LOX
      expression impaired by proatherogenic risk factors. METHODS AND RESULTS: We
      observed that pharmacological concentrations of statins (atorvastatin and
      simvastatin) modulated LOX transcriptional activity, counteracting the down
      regulation of LOX (at the mRNA, protein, and activity level) caused by tumour
      necrosis factor-alpha (TNFalpha) in porcine, bovine, and human aortic endothelial
      cells. Geranylgeraniol but not farnesol reversed this effect, suggesting the
      involvement of geranylgeranylated proteins. In accordance, inhibitors of RhoA/Rho
      kinase also counteracted LOX down-regulation caused by TNFalpha, and over
      expression of a RhoA dominant-negative mutant mimicked statin effects. Statins
      were also able to counteract the decrease in LOX expression produced by
      atherogenic concentrations of LDL by a similar mechanism and to partially prevent
      the increase in endothelial permeability elicited by these lipoproteins. Finally,
      in the in vivo porcine model of hypercholesterolaemia, we observed that statins
      abrogated the reduction of vascular LOX expression triggered by high plasma
      levels of LDL. CONCLUSION: These data indicate that statins normalize vascular
      LOX expression altered by atherogenic risk factors through a RhoA/Rho kinase
      dependent mechanism. Thus, modulation of LOX by statins could contribute to
      vascular protection and to the cardiovascular risk reduction achieved by this
      therapy.

PMID- 19406913
TI  - Measurement of insulin immunoreactivity in human plasma and serum.

PMID- 19406914
TI  - Cross-reactivity of naloxone with oxycodone immunoassays: implications for
      individuals taking Suboxone.

PMID- 19406912
TI  - Rho kinase-1 mediates cardiac fibrosis by regulating fibroblast precursor cell
      differentiation.
AB  - AIMS: Highly proliferative, CD34+/CD45+ fibroblasts derived from monocytic, blood
      borne precursor cells play a critical role in the development of fibrosis in a
      murine ischaemic/reperfusion cardiomyopathy (I/RC) model. The differentiation of
      human monocytes into fibroblasts in vitro occurs after transendothelial migration
      (TEM) induced by monocyte chemoattractant protein 1 (MCP-1). Because Rho
      associated kinase-1 (ROCK-1) has been implicated in fibrosis and leukocyte TEM,
      we investigated its involvement in I/RC. METHODS AND RESULTS: We subjected mice
      with genetic deletion of ROCK-1 to I/RC. We found that ROCK-1(-/-) mice did not
      develop the fibrosis and cardiac dysfunction characteristic for I/RC: compared
      with wild-type, ROCK-1(-/-) hearts showed markedly lower numbers of I/RC-induced
      alpha-smooth muscle actin+ fibroblasts and CD34+/CD45+ fibroblast precursors.
      Isolated cardiac fibroblasts from ROCK-1(-/-) mice undergoing I/RC were large and
      slowly proliferating, similar to fibroblasts isolated from sham-treated hearts.
      We also performed in vitro assays in which human peripheral blood mononuclear
      cells (PBMC) migrated through endothelial cells in response to MCP-1. Prior to
      migration, PBMC were incubated with ROCK-1-targeting small interfering RNA to
      silence ROCK-1 expression. We found that an 80% reduction of ROCK-1 protein did
      not inhibit TEM, but significantly reduced the amount of mononuclear cells that
      differentiated into fibroblasts by >20-fold. CONCLUSION: Our data implicate an
      important role for ROCK-1 in the differentiation, but not in the TEM of monocytes
      that mature into cardiac fibroblasts. These cells mediate non-adaptive fibrosis.

PMID- 19406915
TI  - Glomerular filtration rate is a confounder for the measurement of soluble
      mesothelin in serum.

PMID- 19406916
TI  - Hepcidin as a predictor of response to epoetin therapy in anemic cancer patients.
AB  - BACKGROUND: Hepcidin is thought to be the central regulator of iron metabolism.
      Iron deficiency is associated with low hepcidin concentrations, and anemia in
      patients with cancer is associated with high concentrations of hepcidin. STUDY
      OBJECTIVES: Our main objective was to assess the potential role of hepcidin for
      predicting response to epoetin therapy in anemic cancer patients. We also aimed
      to identify a cutoff value for hepcidin as a potential predictive marker for
      response to epoetin therapy. METHODS: Using data from 525 anemic cancer patients
      enrolled in 5 studies, we assessed serum hepcidin concentrations in 408 of these
      patients at baseline and analyzed pooled data from the 408 patients. The analysis
      population was separated into 2 categories using a threshold hepcidin
      concentration of 13 nmol/L: low hepcidin (< 13 nmol/L) and high hepcidin (> or =
      13 nmol/L). RESULTS: A significantly higher percentage of responders (defined as
      hemoglobin increase > or = 10 g/L or > or = 20 g/L from baseline) was observed in
      the low hepcidin group compared with the high hepcidin group (P = 0.04 for > or =
      10 g/L increase and P = 0.009 for > or = 20 g/L from baseline). There was also a
      statistically significant difference between the 2 groups for hematopoietic
      response (hemoglobin rise at least once > or = 20 g/L from baseline or at least
      once > or = 120 g/L) to epoetin therapy (P = 0.0004). CONCLUSIONS: The results of
      this analysis suggest a potential role of hepcidin serum concentrations in
      predicting the response to epoetin therapy.

PMID- 19406917
TI  - Identification and prevention of genotyping errors caused by G-quadruplex- and i
      motif-like sequences.
AB  - BACKGROUND: Reliable PCR amplification of DNA fragments is the prerequisite for
      most genetic assays. We investigated the impact of G-quadruplex- or i-motif-like
      sequences on the reliability of PCR-based genetic analyses. METHODS: We found the
      sequence context of a common intronic polymorphism in the MEN1 gene (multiple
      endocrine neoplasia I) to be the cause of systematic genotyping errors by
      inducing preferential amplification of one allelic variant [allele dropout
      (ADO)]. Bioinformatic analyses and pyrosequencing-based allele quantification
      enabled the identification of the underlying DNA structures. RESULTS: We showed
      that G-quadruplex- or i-motif-like sequences can reproducibly cause ADO. In these
      cases, amplification efficiency strongly depends on the PCR enzyme and buffer
      conditions, the magnesium concentration in particular. In a randomly chosen
      subset of candidate single-nucleotide polymorphisms (SNPs) defined by properties
      deduced from 2 originally identified ADO cases, we confirmed preferential PCR
      amplification in up to 50% of the SNPs. We subsequently identified G-quadruplex
      and i-motifs harboring a SNP that alters the typical motif as the cause of this
      phenomenon, and a genomewide search based on the respective motifs predicted 0.5%
      of all SNPs listed by dbSNP and Online Mendelian Inheritance in Man to be
      potentially affected. CONCLUSIONS: Undetected, the described phenomenon produces
      systematic errors in genetic analyses that may lead to misdiagnoses in clinical
      settings. PCR products should be checked for G-quadruplex and i-motifs to avoid
      the formation of ADO-causing secondary structures. Truly affected assays can then
      be identified by a simple experimental procedure, which simultaneously provides
      the solution to the problem.

PMID- 19406918
TI  - Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer.
AB  - BACKGROUND: The presence of aberrantly methylated SEPT9 DNA in plasma is highly
      correlated with the occurrence of colorectal cancer. We report the development of
      a new SEPT9 biomarker assay and its validation in case-control studies. The
      development of such a minimally invasive blood-based test may help to reduce the
      current gap in screening coverage. METHODS: A new SEPT9 DNA methylation assay was
      developed for plasma. The assay comprised plasma DNA extraction, bisulfite
      conversion of DNA, purification of bisulfite-converted DNA, quantification of
      converted DNA by real-time PCR, and measurement of SEPT9 methylation by real-time
      PCR. Performance of the SEPT9 assay was established in a study of 97 cases with
      verified colorectal cancer and 172 healthy controls as verified by colonoscopy.
      Performance based on predetermined algorithms was validated in an independent
      blinded study with 90 cases and 155 controls. RESULTS: The SEPT9 assay workflow
      yielded 1.9 microg/L (CI 1.3-3.0) circulating plasma DNA following bisulfite
      conversion, a recovery of 45%-50% of genomic DNA, similar to yields in previous
      studies. The SEPT9 assay successfully identified 72% of cancers at a specificity
      of 93% in the training study and 68% of cancers at a specificity of 89% in the
      testing study. CONCLUSIONS: Circulating methylated SEPT9 DNA, as measured in the
      new (m)SEPT9 assay, is a valuable biomarker for minimally invasive detection of
      colorectal cancer. The new assay is amenable to automation and standardized use
      in the clinical laboratory.

PMID- 19406919
TI  - Comparing methods for accounting for seasonal variability in a biomarker when
      only a single sample is available: insights from simulations based on serum 25
      hydroxyvitamin d.
AB  - In biomarker-disease association studies, the long-term average level of a
      biomarker is often considered the optimal measure of exposure. Long-term average
      levels may not be accurately measured from a single sample, however, because of
      systematic temporal variation. For example, serum 25-hydroxyvitamin D (25(OH)D)
      concentrations may fluctuate because of seasonal variation in sun exposure.
      Association studies of 25(OH)D and cancer risk have used different strategies to
      minimize bias from such seasonal variation, including adjusting for date of
      sample collection (DOSC), often after matching on DOSC, and/or using season
      specific cutpoints to assign subjects to exposure categories. To evaluate and
      understand the impact of such strategies on potential bias, the authors simulated
      a population in which 25(OH)D levels varied between individuals and by season,
      and disease risk was determined by long-term average 25(OH)D. Ignoring temporal
      variation resulted in bias toward the null. When cutpoints that did not account
      for DOSC were used, adjustment for DOSC sometimes resulted in bias away from the
      null. Using season- or month-specific cutpoints reduced bias toward the null and
      did not cause bias away from the null. To avoid potential bias away from the
      null, using season- or month-specific cutpoints may be preferable to adjusting
      for DOSC.

PMID- 19406920
TI  - Is there a clear threshold for fasting plasma glucose that differentiates between
      those with and without neuropathy and chronic kidney disease?: the Singapore
      Prospective Study Program.
AB  - Recent studies suggest that no distinct glycemic threshold consistently
      differentiates individuals with or without retinopathy. The authors sought to
      determine whether the same was true for other microvascular complications. They
      studied 5,094 participants with fasting plasma glucose values and concurrent
      microvascular complications from 4 previous cross-sectional surveys carried out
      in Singapore (1982-1998) who attended a follow-up examination in 2004-2007.
      Peripheral neuropathy was diagnosed based on abnormal responses to a 10-g
      monofilament or neurothesiometer test. Chronic kidney disease was defined in
      various ways by using albuminuria (urine albumin:creatinine ratio >30 microg/mg)
      and estimated glomerular filtration rate, alone and in combination. Prevalence of
      peripheral neuropathy was 7.5%. For chronic kidney disease, prevalence of
      albuminuria only was 10.5%, estimated glomerular filtration rate of <60 mL/minute
      per 1.73 m(2) only was 4.1%, and both was 2.1%. Prevalence of peripheral
      neuropathy and chronic kidney disease gradually increased in relation to fasting
      plasma glucose, beginning at levels below the existing diagnostic threshold for
      diabetes mellitus of 7.0 mmol/L (126 mg/dL). For chronic kidney disease, these
      associations persisted after adjustment for age, gender, ethnic group, and
      hypertension. Current diagnostic thresholds for diabetes mellitus have limited
      sensitivity for identifying individuals with these microvascular complications.
      Ascertaining these individuals may require development and application of novel
      screening strategies.

PMID- 19406921
TI  - Folding of the cocaine aptamer studied by EPR and fluorescence spectroscopies
      using the bifunctional spectroscopic probe C.
AB  - The cocaine aptamer is a DNA molecule that binds cocaine at the junction of three
      helices. The bifunctional spectroscopic probe C was incorporated independently
      into three different positions of the aptamer and changes in structure and
      dynamics upon addition of the cocaine ligand were studied. Nucleoside C contains
      a rigid nitroxide spin label and can be studied directly by electron paramagnetic
      resonance (EPR) spectroscopy and fluorescence spectroscopy after reduction of the
      nitroxide to yield the fluoroside C(f). Both the EPR and the fluorescence data
      for aptamer 2 indicate that helix III is formed before cocaine binding. Upon
      addition of cocaine, increased fluorescence of a fully base-paired C(f), placed
      at the three-way junction in helix III, was observed and is consistent with a
      helical tilt from a coaxial stack of helices II and III. EPR and fluorescence
      data clearly show that helix I is formed upon addition of cocaine, concomitant
      with the formation of the Y-shaped three-way helical junction. The EPR data
      indicate that nucleotides in helix I are more mobile than nucleotides in regular
      duplex regions and may reflect increased dynamics due to the short length of
      helix I.

PMID- 19406922
TI  - SplitPocket: identification of protein functional surfaces and characterization
      of their spatial patterns.
AB  - SplitPocket (http://pocket.uchicago.edu/) is a web server to identify functional
      surfaces of protein from structure coordinates. Using the Alpha Shape Theory, we
      previously developed an analytical approach to identify protein functional
      surfaces by the geometric concept of a split pocket, which is a pocket split by a
      binding ligand. Our geometric approach extracts site-specific spatial information
      from coordinates of structures. To reduce the search space, probe radii are
      designed according to the physicochemical textures of molecules. The method uses
      the weighted Delaunay triangulation and the discrete flow algorithm to obtain
      geometric measurements and spatial patterns for each predicted pocket. It can
      also measure the hydrophobicity on a surface patch. Furthermore, we quantify the
      evolutionary conservation of surface patches by an index derived from the entropy
      scores in HSSP (homology-derived secondary structure of proteins). We have used
      the method to examine approximately 1.16 million potential pockets and identified
      the split pockets in >26,000 structures in the Protein Data Bank. This integrated
      web server of functional surfaces provides a source of spatial patterns to serve
      as templates for predicting the functional surfaces of unbound structures
      involved in binding activities. These spatial patterns should also be useful for
      protein functional inference, structural evolution and drug design.

PMID- 19406923
TI  - A glycolytic burst drives glucose induction of global histone acetylation by
      picNuA4 and SAGA.
AB  - Little is known about what enzyme complexes or mechanisms control global lysine
      acetylation in the amino-terminal tails of the histones. Here, we show that
      glucose induces overall acetylation of H3 K9, 18, 27 and H4 K5, 8, 12 in
      quiescent yeast cells mainly by stimulating two KATs, Gcn5 and Esa1. Genetic and
      pharmacological perturbation of carbon metabolism, combined with (1)H-NMR
      metabolic profiling, revealed that glucose induction of KAT activity directly
      depends on increased glucose catabolism. Glucose-inducible Esa1 and Gcn5
      activities predominantly reside in the picNuA4 and SAGA complexes, respectively,
      and act on chromatin by an untargeted mechanism. We conclude that direct
      metabolic regulation of globally acting KATs can be a potent driving force for
      reconfiguration of overall histone acetylation in response to a physiological
      cue.

PMID- 19406924
TI  - DIANA-microT web server: elucidating microRNA functions through target
      prediction.
AB  - Computational microRNA (miRNA) target prediction is one of the key means for
      deciphering the role of miRNAs in development and disease. Here, we present the
      DIANA-microT web server as the user interface to the DIANA-microT 3.0 miRNA
      target prediction algorithm. The web server provides extensive information for
      predicted miRNA:target gene interactions with a user-friendly interface,
      providing extensive connectivity to online biological resources. Target gene and
      miRNA functions may be elucidated through automated bibliographic searches and
      functional information is accessible through Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathways. The web server offers links to nomenclature, sequence
      and protein databases, and users are facilitated by being able to search for
      targeted genes using different nomenclatures or functional features, such as the
      genes possible involvement in biological pathways. The target prediction
      algorithm supports parameters calculated individually for each miRNA:target gene
      interaction and provides a signal-to-noise ratio and a precision score that helps
      in the evaluation of the significance of the predicted results. Using a set of
      miRNA targets recently identified through the pSILAC method, the performance of
      several computational target prediction programs was assessed. DIANA-microT 3.0
      achieved there with 66% the highest ratio of correctly predicted targets over all
      predicted targets. The DIANA-microT web server is freely available at
      www.microrna.gr/microT.

PMID- 19406925
TI  - WhichGenes: a web-based tool for gathering, building, storing and exporting gene
      sets with application in gene set enrichment analysis.
AB  - WhichGenes is a web-based interactive gene set building tool offering a very
      simple interface to extract always-updated gene lists from multiple databases and
      unstructured biological data sources. While the user can specify new gene sets of
      interest by following a simple four-step wizard, the tool is able to run several
      queries in parallel. Every time a new set is generated, it is automatically added
      to the private gene-set cart and the user is notified by an e-mail containing a
      direct link to the new set stored in the server. WhichGenes provides
      functionalities to edit, delete and rename existing sets as well as the
      capability of generating new ones by combining previous existing sets
      (intersection, union and difference operators). The user can export his sets
      configuring the output format and selecting among multiple gene identifiers. In
      addition to the user-friendly environment, WhichGenes allows programmers to
      access its functionalities in a programmatic way through a Representational State
      Transfer web service. WhichGenes front-end is freely available at
      http://www.whichgenes.org/, WhichGenes API is accessible at
      http://www.whichgenes.org/api/.

PMID- 19406926
TI  - One RNA plays three roles to provide catalytic activity to a group I intron
      lacking an endogenous internal guide sequence.
AB  - Catalytic RNA molecules possess simultaneously a genotype and a phenotype.
      However, a single RNA genotype has the potential to adopt two or perhaps more
      distinct phenotypes as a result of differential folding and/or catalytic
      activity. Such multifunctionality would be particularly significant if the
      phenotypes were functionally inter-related in a common biochemical pathway. Here,
      this phenomenon is demonstrated by the ability of the Azoarcus group I ribozyme
      to function when its canonical internal guide sequence (GUG) has been removed
      from the 5' end of the molecule, and added back exogenously in trans. The
      presence of GUG triplets in non-covalent fragments of the ribozyme allow trans
      splicing to occur in both a reverse splicing assay and a covalent self-assembly
      assay in which the internal guide sequence (IGS)-less ribozyme can put itself
      together from two of its component pieces. Analysis of these reactions indicates
      that a single RNA fragment can perform up to three distinct roles in a reaction:
      behaving as a portion of a catalyst, behaving as a substrate, and providing an
      exogenous IGS. This property of RNA to be multifunctional in a single reaction
      pathway bolsters the probability that a system of self-replicating molecules
      could have existed in an RNA world during the origins of life on the Earth.

PMID- 19406927
TI  - GeNMR: a web server for rapid NMR-based protein structure determination.
AB  - GeNMR (GEnerate NMR structures) is a web server for rapidly generating accurate
      3D protein structures using sequence data, NOE-based distance restraints and/or
      NMR chemical shifts as input. GeNMR accepts distance restraints in XPLOR or CYANA
      format as well as chemical shift files in either SHIFTY or BMRB formats. The web
      server produces an ensemble of PDB coordinates for the protein within 15-25 min,
      depending on model complexity and completeness of experimental restraints. GeNMR
      uses a pipeline of several pre-existing programs and servers to calculate the
      actual protein structure. In particular, GeNMR combines genetic algorithms for
      structure optimization along with homology modeling, chemical shift threading,
      torsion angle and distance predictions from chemical shifts/NOEs as well as
      ROSETTA-based structure generation and simulated annealing with XPLOR-NIH to
      generate and/or refine protein coordinates. GeNMR greatly simplifies the task of
      protein structure determination as users do not have to install or become
      familiar with complex stand-alone programs or obscure format conversion
      utilities. Tests conducted on a sample of 90 proteins from the BioMagResBank
      indicate that GeNMR produces high-quality models for all protein queries,
      regardless of the type of NMR input data. GeNMR was developed to facilitate
      rapid, user-friendly structure determination of protein structures via NMR
      spectroscopy. GeNMR is accessible at http://www.genmr.ca.

PMID- 19406928
TI  - The Microbe browser for comparative genomics.
AB  - The Microbe browser is a web server providing comparative microbial genomics
      data. It offers comprehensive, integrated data from GenBank, RefSeq, UniProt,
      InterPro, Gene Ontology and the Orthologs Matrix Project (OMA) database,
      displayed along with gene predictions from five software packages. The Microbe
      browser is daily updated from the source databases and includes all completely
      sequenced bacterial and archaeal genomes. The data are displayed in an easy-to
      use, interactive website based on Ensembl software. The Microbe browser is
      available at http://microbe.vital-it.ch/. Programmatic access is available
      through the OMA application programming interface (API) at http://microbe.vital
      it.ch/api.

PMID- 19406930
TI  - Peroxiredoxin I contributes to TRAIL resistance through suppression of redox
      sensitive caspase activation in human hepatoma cells.
AB  - Reactive oxygen species (ROS) have been implicated in tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) resistance of many cancers. We
      evaluated the role of peroxiredoxin (Prx) I in TRAIL resistance governed by
      coupling of nicotinamide adenosine dinucleotide phosphate oxidase (Nox)-derived
      ROS signaling with the p38 mitogen-activated protein kinase (MAPK)/caspase
      signaling cascade in liver cancer cells. Upregulated Prx I expression was found
      in neoplastic regions of human patient liver, and Prx I knockdown resulted in
      accelerated TRAIL-induced cell death in SK-Hep-1 human hepatoma cells. The TRAIL
      cytotoxicity by Prx I knockdown was dependent on activation of caspase-8/3
      cascades, which was ablated by addition of inhibitors for p38 MAPK, ROS or Nox,
      suggesting the association with Nox-driven redox signaling. Furthermore, we found
      that Nox4 was constitutively expressed in both SK-Hep-1 cells and tumor regions
      of patient livers, knockdown of Nox4 expression could alleviate ROS generation
      and TRAIL-mediated cytotoxicity. In accordance with previous findings, increased
      activation of both p38 MAPK and caspase cascades by Prx I knockdown was inhibited
      by either Nox4 knockdown or SB203580 addition. Collectively, these data suggest
      that Prx I functions to block propagation of Nox-derived ROS signaling to the p38
      MAPK/caspase/cell death cascade during TRAIL treatment and also provides a
      molecular mechanism by which Prx I contributes to TRAIL resistance in liver
      cancers.

PMID- 19406929
TI  - Replication fork reversal and the maintenance of genome stability.
AB  - The progress of replication forks is often threatened in vivo, both by DNA damage
      and by proteins bound to the template. Blocked forks must somehow be restarted,
      and the original blockage cleared, in order to complete genome duplication,
      implying that blocked fork processing may be critical for genome stability. One
      possible pathway that might allow processing and restart of blocked forks,
      replication fork reversal, involves the unwinding of blocked forks to form four
      stranded structures resembling Holliday junctions. This concept has gained
      increasing popularity recently based on the ability of such processing to explain
      many genetic observations, the detection of unwound fork structures in vivo and
      the identification of enzymes that have the capacity to catalyse fork regression
      in vitro. Here, we discuss the contexts in which fork regression might occur, the
      factors that may promote such a reaction and the possible roles of replication
      fork unwinding in normal DNA metabolism.

PMID- 19406931
TI  - Vitamin C and alpha-naphthoflavone prevent estrogen-induced mammary tumors and
      decrease oxidative stress in female ACI rats.
AB  - The mechanisms underlying the pathogenesis of estrogen-induced breast
      carcinogenesis remain unclear. The present study investigated the roles of
      estrogen metabolism and oxidative stress in estrogen-mediated mammary
      carcinogenesis in vivo. Female August Copenhagen Irish (ACI) rats were treated
      with 17beta-estradiol (E(2)), the antioxidant vitamin C, the estrogen metabolic
      inhibitor alpha-naphthoflavone (ANF), or cotreated with E(2) + vitamin C or E(2)
      + ANF for up to 8 months. E(2) (3 mg) was administered as an subcutaneous
      implant, ANF was given via diet (0.2%) and vitamin C (1%) was added to drinking
      water. At necropsy, breast tumor incidence in the E(2), E(2) + vitamin C and E(2)
      + ANF groups was 82, 29 and 0%, respectively. Vitamin C and ANF attenuated E(2)
      induced alterations in oxidative stress markers in breast tissue, including 8-iso
      prostane F(2alpha) formation and changes in the activities of antioxidant enzymes
      superoxide dismutase and glutathione peroxidase. Quantification of 2
      hydroxyestradiol (2-OHE(2)) and 4-hydroxyestradiol (4-OHE(2)) formation in breast
      tissue confirmed that ANF inhibited 4-hydroxylation of E(2) and decreased
      formation of the highly carcinogenic 4-OHE(2). These results demonstrate that
      antioxidant vitamin C reduces the incidence of estrogen-induced mammary tumors,
      increases tumor latency and decreases oxidative stress in vivo. Further, our data
      indicate that ANF completely abrogates breast cancer development in ACI rats. The
      present study is the first to demonstrate the inhibition of breast carcinogenesis
      by antioxidant vitamin C or the estrogen metabolic inhibitor ANF in an animal
      model of estrogen-induced mammary carcinogenesis. Taken together, these results
      suggest that E(2) metabolism and oxidant stress are critically involved in
      estrogen-induced breast carcinogenesis.

PMID- 19406932
TI  - The isatin-Schiff base copper(II) complex Cu(isaepy)2 acts as delocalized
      lipophilic cation, yields widespread mitochondrial oxidative damage and induces
      AMP-activated protein kinase-dependent apoptosis.
AB  - We previously demonstrated that Bis[(2-oxindol-3-ylimino)-2-(2
      aminoethyl)pyridine-N,N']copper(II) [Cu(isaepy)(2)] was an efficient inducer of
      the apoptotic mitochondrial pathway. Here, we deeply dissect the mechanisms
      underlying the ability of Cu(isaepy)(2) to cause mitochondriotoxicity. In
      particular, we demonstrate that Cu(isaepy)(2) increases NADH-dependent oxygen
      consumption of isolated mitochondria and that this phenomenon is associated with
      oxy-radical production and insensitive to adenosine diphosphate. These data
      indicate that Cu(isaepy)(2) behaves as an uncoupler and this property is also
      confirmed in cell systems. Particularly, SH-SY5Y cells show: (i) an early loss of
      mitochondrial transmembrane potential; (ii) a decrease in the expression levels
      of respiratory complex components and (iii) a significant adenosine triphosphate
      (ATP) decrement. The causative energetic impairment mediated by Cu(isaepy)(2) in
      apoptosis is confirmed by experiments carried out with rho(0) cells, or by
      glucose supplementation, where cell death is significantly inhibited. Moreover,
      gastric and cervix carcinoma AGS and HeLa cells, which rely most of their ATP
      production on oxidative phosphorylation, show a marked sensitivity toward
      Cu(isaepy)(2). Adenosine monophosphate-activated protein kinase (AMPK), which is
      activated by events increasing the adenosine monophosphate:ATP ratio, is deeply
      involved in the apoptotic process because the overexpression of its
      dominant/negative form completely abolishes cell death. Upon glucose
      supplementation, AMPK is not activated, confirming its role as fuel-sensing
      enzyme that positively responds to Cu(isaepy)(2)-mediated energetic impairment by
      committing cells to apoptosis. Overall, data obtained indicate that Cu(isaepy)(2)
      behaves as delocalized lipophilic cation and induces mitochondrial-sited reactive
      oxygen species production. This event results in mitochondrial dysfunction and
      ATP decrease, which in turn triggers AMPK-dependent apoptosis.

PMID- 19406933
TI  - Tolfenamic acid inhibits esophageal cancer through repression of specificity
      proteins and c-Met.
AB  - The non-steroidal anti-inflammatory drug tolfenamic acid (TA) inhibits
      proliferation of SEG-1 and BIC-1 esophageal cancer cells with half-maximal growth
      inhibitory concentration values of 36 and 48 muM, respectively. TA also increased
      Annexin V staining in both cell lines, indicative of proapoptotic activity.
      Treatment of SEG-1 and BIC-1 cells with TA for up to 72 h decreased expression of
      specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and this was
      accompanied by decreased expression of the well-characterized Sp-regulated genes
      cyclin D1, vascular endothelial growth factor and survivin. TA also decreased
      hepatocyte growth factor receptor, (c-Met), a receptor tyrosine kinase that is
      overexpressed in esophageal cancer cells and tumors and is an important drug
      target. Knockdown of Sp1, Sp3 and Sp4 by RNA interference in SEG-1 and BIC-1
      cells also decreased c-Met expression, demonstrating that c-Met is an Sp
      regulated gene in esophageal cancer cells. Sp1 was overexpressed in esophageal
      cancer cells and tumors and increased Sp1 staining was observed in esophageal
      tumors from patients. TA (20 mg/kg/day) also decreased tumor growth and weight in
      athymic nude mice bearing SEG-1 cells as xenografts and this was accompanied by
      increased apoptosis and decreased Sp1 and c-Met staining in tumors from treated
      mice. Thus, TA-dependent downregulation of Sp transcription factors and c-Met
      defines a novel chemotherapeutic approach for treatment of esophageal cancer.

PMID- 19406934
TI  - HapMap-based study of the DNA repair gene ERCC2 and lung cancer susceptibility in
      a Chinese population.
AB  - DNA repair genes have been proposed as candidate cancer susceptibility genes. The
      excision repair cross-complementing rodent repair deficiency, complementation
      group 2 (ERCC2)/xeroderma pigmentosum complementary group D (XPD) protein is
      considered to be a key enzyme in nucleotide excision repair (NER) pathway. To
      elucidate whether common ERCC2 variants are associated with lung cancer
      susceptibility, we conducted a case-control study consisting of 339 cases with
      primary lung cancer and 358 controls matched on age, gender and ethnicity in a
      Chinese population. Six haplotype tagging single-nucleotide polymorphisms
      (htSNPs) (rs238403, rs50871, rs3916840, rs238415, rs3916874 and rs1799787) from
      HapMap database were analyzed, which provide an almost complete coverage of the
      genetic variations in the ERCC2 gene. Although none of the six htSNPs was
      individually associated with lung cancer risk, we found that two ERCC2 haplotypes
      were associated with risk of lung cancer. Haplotype 4 defined by rs238403T
      rs50871T-rs3916840C-rs238415C-rs3916874G-rs1799787C and haplotype 7 defined by
      rs238403C-rs50871G-rs3916840C-rs238415C-rs3916874G-rs1799787C were strongly
      associated with an increased risk of lung cancer [odds ratio, OR (95% confidence
      interval, CI) = 2.62 (1.53-4.50), P = 0.0003 for hap4; OR (95% CI) = 3.01 (1.36
      6.63), P = 0.004 for hap7]. Furthermore, diplotype analyses also strengthened the
      significant associations of risk haplotype 4 [OR (95% CI) = 3.56 (2.12-5.87), P <
      0.001] or risk haplotype 7 [OR (95% CI) = 3.38 (1.75-6.55), P < 0.001] and lung
      cancer. Analysis of linkage disequilibrium (LD) also confirmed that considerable
      LD exists between the pairs of the six htSNPs within ERCC2. These results
      suggested that the risk subhaplotypes cosegregate with one or more biologically
      functional polymorphisms. Our results provide evidence to support a role for
      ERCC2 in lung cancer development in a Chinese population.

PMID- 19406937
TI  - Genomic drift and evolution of microsatellite DNAs in human populations.
AB  - In recent years, copy number variation (CNV) of DNA segments has become a hot
      topic in the study of genetic variation, and a large amount of CNVs has been
      uncovered in human populations. The CNVs involving the smallest units of DNA
      segments are microsatellite DNAs, and the evolutionary change of microsatellite
      DNAs is believed to occur mostly by the increase or decrease of one repeat unit
      at a time in a more or less neutral fashion. If we note that eukaryotic genomes
      contain millions of microsatellite loci, this pattern of nucleotide change is
      expected to generate random changes of genome size, that is, genomic drift, and
      will provide a neutral model of CNV evolution. We therefore investigated the
      amount of variation of the total number of repeats (TNR) per individual concerned
      with 145 microsatellite loci in three human populations, Africans, Europeans, and
      Asians. It was shown that the TNR follows the normal distribution in all three
      populations and that the extent of variation of TNR is more than 50% greater in
      Africans than in Europeans and Asians as expected from the hypothesis of African
      origin of modern humans. If we consider all microsatellite loci in the human
      genome and compute the variation of the total number of nucleotides involved
      (TNN), it is possible to study the contribution of microsatellite loci to the
      genome size variation. This study has shown that the genome sizes of human
      individuals are affected considerably by genomic drift of microsatellite DNA
      alone. This pattern of evolution is similar to that of olfactory receptor (OR)
      genes previously studied in human populations and support the idea that the
      number of OR genes has evolved in a more or less neutral fashion. However, this
      conclusion does not necessarily apply to the genomewide CNVs of various DNA
      segments, and it appears that long variant DNA fragments are deleterious and
      under purifying selection.

PMID- 19406938
TI  - Targeted disruption of carcinoembryonic antigen-related cell adhesion molecule 1
      promotes diet-induced hepatic steatosis and insulin resistance.
AB  - Carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) is a cell
      adhesion molecule within the Ig superfamily. The Tyr-phosphorylated isoform of
      CC1 (CC1-L) plays an important metabolic role in the regulation of hepatic
      insulin clearance. In this report, we show that CC1-deficient (Cc1(-/-)) mice are
      prone to hepatic steatosis, as revealed by significantly elevated hepatic
      triglyceride and both total and esterified cholesterol levels compared with age
      matched wild-type controls. Cc1(-/-) mice were also predisposed to lipid-induced
      hepatic steatosis and dysfunction as indicated by their greater susceptibility to
      store lipids and express elevated levels of enzymatic markers of liver damage
      after chronic feeding of a high-fat diet. Hepatic steatosis in the Cc1(-/-) mice
      was linked to a significant increase in the expression of key lipogenic (fatty
      acid synthase, acetyl CoA carboxylase) and cholesterol synthetic (3-hydroxy-3
      methylglutaryl-coenzyme A reductase) enzymes under the control of sterol
      regulatory element binding proteins-1c and -2 transcription factors. Cc1(-/-)
      mice also exhibited impaired insulin clearance, glucose intolerance, liver
      insulin resistance, and elevated hepatic expression of the key gluconeogenic
      transcriptional activators peroxisome proliferator-activated receptor-gamma
      coactivator-1 and Forkhead box O1. Lack of CC1 also exacerbated both glucose
      intolerance and hepatic insulin resistance induced by high-fat feeding, but
      insulin clearance was not further deteriorated in the high-fat-fed Cc1(-/-) mice.
      In conclusion, our data indicate that CC1 is a key regulator of hepatic
      lipogenesis and that Cc1(-/-) mice are predisposed to liver steatosis, leading to
      hepatic insulin resistance and liver damage, particularly when chronically
      exposed to dietary fat.

PMID- 19406939
TI  - Gastric mammalian target of rapamycin signaling regulates ghrelin production and
      food intake.
AB  - Ghrelin, a gastric hormone, provides a hunger signal to the central nervous
      system to stimulate food intake. Mammalian target of rapamycin (mTOR) is an
      intracellular fuel sensor critical for cellular energy homeostasis. Here we
      showed the reciprocal relationship of gastric mTOR signaling and ghrelin during
      changes in energy status. mTOR activity was down-regulated, whereas gastric
      preproghrelin and circulating ghrelin were increased by fasting. In db/db mice,
      gastric mTOR signaling was enhanced, whereas gastric preproghrelin and
      circulating ghrelin were decreased. Inhibition of the gastric mTOR signaling by
      rapamycin stimulated the expression of gastric preproghrelin and ghrelin mRNA and
      increased plasma ghrelin in both wild-type and db/db mice. Activation of the
      gastric mTOR signaling by l-leucine decreased the expression of gastric
      preproghrelin and the level of plasma ghrelin. Overexpression of mTOR attenuated
      ghrelin promoter activity, whereas inhibition of mTOR activity by overexpression
      of TSC1 or TSC2 increased its activity. Ghrelin receptor antagonist d-Lys-3-GH
      releasing peptide-6 abolished the rapamycin-induced increment in food intake
      despite that plasma ghrelin remained elevated. mTOR is therefore a gastric fuel
      sensor whose activity is linked to the regulation of energy intake through
      ghrelin.

PMID- 19406940
TI  - Computational and functional analysis of growth hormone (GH)-regulated genes
      identifies the transcriptional repressor B-cell lymphoma 6 (Bc16) as a
      participant in GH-regulated transcription.
AB  - For insight into transcriptional mechanisms mediating physiological responses to
      GH, data mining was performed on a profile of GH-regulated genes induced or
      inhibited at different times in highly responsive 3T3-F442A adipocytes. Gene set
      enrichment analysis indicated that GH-regulated genes are enriched in pathways
      including phosphoinositide and insulin signaling and suggested that suppressor of
      cytokine signaling 2 (SOCS2) and phosphoinositide 3' kinase regulatory subunit
      p85alpha (Pik3r1) are important targets. Model-based Chinese restaurant
      clustering identified a group of genes highly regulated by GH at times consistent
      with its key physiological actions. This cluster included IGF-I, phosphoinositide
      3' kinase p85alpha, SOCS2, and cytokine-inducible SH2-containing protein. It also
      contains the most strongly repressed gene in the profile, B cell lymphoma 6
      (Bcl6), a transcriptional repressor. Quantitative real-time PCR verified the
      strong decrease in Bcl6 mRNA after GH treatment and induction of the other genes
      in the cluster. Transcriptional network analysis of the genes implicated signal
      transducer and activator of transcription (Stat) 5 as hub regulating the most
      responsive genes, Igf1, Socs2, Cish, and Bcl6. Transcriptional activation
      analysis demonstrated that Bcl6 inhibits SOCS2-luciferase and blunts its
      stimulation by GH. Occupancy of endogenous Bcl6 on SOCS2 DNA decreased after GH
      treatment, whereas occupancy of Stat5 increased concomitantly. Thus, GH-mediated
      inhibition of Bcl6 expression may reverse the repression of SOCS2 and facilitate
      SOCS2 activation by GH. Together these analyses identify Bcl6 as a participant in
      GH-regulated gene expression and suggest an interplay between the repressor Bcl6
      and the activator Stat5 in regulating genes, which contribute to GH responses.

PMID- 19406942
TI  - Thymocyte-synthesized glucocorticoids play a role in thymocyte homeostasis and
      are down-regulated by adrenocorticotropic hormone.
AB  - Thymocytes from adult mice synthesize glucocorticoids (GCs), and some data
      indicate a role for this hormone production in thymic homeostasis. Here we
      present further support for this view by showing that the dramatic increase in
      thymocyte number seen after adrenalectomy (ADX) does not correlate with the
      decrease in systemic GCs but rather with an ACTH-mediated down-regulation of GC
      synthesis in thymocytes. High ACTH concentrations caused by ADX in wild-type mice
      down-regulated CYP11B1 mRNA expression, encoding the last enzyme required for
      corticosterone synthesis and as a consequence reduced GC synthesis in thymocytes.
      This was not seen in IL-1beta/IL-18 double-knockout mice unable to respond to ADX
      with high ACTH levels. However, if ADX IL-1beta/IL-18 double-knockout mice were
      treated with ACTH, this led to a down-regulation of CYP11B1 and GC synthesis in
      thymocytes. In addition, in vivo treatment of mice with the CYP11B1 antagonist
      metyrapone, without affecting the systemic corticosterone level, increased
      thymocyte numbers and in vitro treatment of isolated thymocytes prevented
      thymocyte loss. Furthermore, in vitro experiments showed that both ACTH and its
      receptor-induced second-messenger molecule cAMP down-regulated mRNA expression of
      critical enzymes in GC steroidogenesis and GC synthesis in thymocytes. We
      conclude that thymocyte-produced GCs are important for the homeostasis of adult
      mouse thymocytes and that high ACTH level, in contrast to stimulating GC
      synthesis in the adrenal glands, has the opposite effect in thymocytes.

PMID- 19406943
TI  - Estrogens augment cell surface TLR4 expression on murine macrophages and regulate
      sepsis susceptibility in vivo.
AB  - Gender-based differences exist in infectious disease susceptibility. In general,
      females generate more robust and potentially protective humoral and cell-mediated
      immune responses after antigenic challenge than their male counterparts.
      Furthermore, evidence is accumulating that sex may also influence the early
      perception of microbial challenges and the generation of inflammatory immune
      responses such as sepsis. These differences have previously been attributed to
      the actions of reproductive hormones. Whereas androgens have been shown to
      suppress acute host immune responses to bacterial endotoxin challenge, estrogens
      have been found to promote increased resistance to bacterial infections. However,
      the mechanisms by which estrogens exert immunoprotective effects have not been
      established. In this study, we investigated the in vivo effects of 17beta
      estradiol on endotoxin susceptibility in mice. Importantly, we have examined the
      actions of this female reproductive hormone on the expression of pattern
      recognition receptors that recognize bacterial endotoxin by key innate immune
      sentinel cells. We show that removal of endogenous estrogens decreases both pro-
      and antiinflammatory cytokine production, with a concomitant reduction in
      circulating levels of lipopolysaccharide-binding protein and cell surface
      expression of Toll-like receptor 4 on murine macrophages. Exogenous in vivo
      replacement of 17beta-estradiol, but not progesterone, significantly elevates
      sera lipopolysaccharide-binding protein levels and cell surface expression of
      Toll-like receptor 4 and CD14 on macrophages. Furthermore, this effect
      corresponds with significantly higher inflammatory cytokine levels after in vivo
      lipopolysaccharide challenge and a marked increase in endotoxin-associated
      morbidity. Taken together, these data provide a potential mechanism underlying
      the immunoenhancing effects of estrogens.

PMID- 19406941
TI  - Activation of the lutropin/choriogonadotropin receptor inhibits apoptosis of
      immature Leydig cells in primary culture.
AB  - We used proliferating primary cultures of immature rat Leydig cells expressing
      the recombinant human LH/choriogonadotropin (CG) receptor (LHR) to test the
      hypothesis that activation of this receptor inhibits apoptosis. We also compared
      the effects of LH/CG with epidermal growth factor (EGF) and IGF-I because these
      have been previously shown to stimulate proliferation and/or inhibit apoptosis in
      Leydig cells. Human CG (hCG), EGF, and IGF-I stimulated the phosphorylation of
      ERK1/2 and Akt in primary cultures of immature rat Leydig cells. These three
      hormones also robustly stimulated thymidine incorporation and inhibited drug
      induced apoptosis. Using selective inhibitors of ERK1/2 (UO126) or Akt
      phosphorylation (LY294002), we show that the ERK1/2 and Akt cascades are both
      involved in the hCG- and EGF-dependent proliferation of Leydig cells, but only
      the ERK1/2 cascade is involved in their antiapoptotic actions. The same strategy
      showed that the proliferative and antiapoptotic actions of IGF-I are mediated
      entirely by the Akt pathway. These results show that activation of the LHR
      inhibits apoptosis in Leydig cells and that it does so through stimulation of the
      ERK1/2 pathway.

PMID- 19406944
TI  - In vivo interaction of steroid receptor coactivator (SRC)-1 and the activation
      function-2 domain of the thyroid hormone receptor (TR) beta in TRbeta E457A knock
      in and SRC-1 knockout mice.
AB  - The activation function-2 (AF-2) domain of the thyroid hormone (TH) receptor (TR)
      beta is a TH-dependent binding site for nuclear coactivators (NCoA), which
      modulate TH-dependent gene transcription. In contrast, the putative AF-1 domain
      is a TH-independent region interacting with NCoA. We determined the specificity
      of the AF-2 domain and NCoA interaction by evaluating thyroid function in mice
      with combined disruption of the AF-2 domain in TRbeta, due to a point mutation
      (E457A), and deletion of one of the NCoAs, steroid receptor coactivator (SRC)-1.
      The E457A mutation was chosen because it abolishes NCoA recruitment in vitro
      while preserving normal TH binding and corepressor interactions resulting in
      resistance to TH. At baseline, disruption of SRC-1 in the homozygous knock-in
      (TRbeta(E457A/E457A)) mice worsened the degree of resistance to TH, resulting in
      increased serum T(4) and TSH. During TH deprivation, disruption of AF-2 and SRC-1
      resulted in a TSH rise 50% of what was seen when AF-2 alone was removed,
      suggesting that SRC-1 was interacting outside of the AF-2 domain. Therefore, 1)
      during TH deprivation, SRC-1 is necessary for activating the hypothalamic
      pituitary-thyroid axis; 2) ligand-dependent repression of TSH requires an intact
      AF-2; and 3) SRC-1 may interact with the another region of the TRbeta or the
      TRalpha to regulate TH action in the pituitary. This report demonstrates the dual
      interaction of NCoA in vivo: the TH-independent up-regulation possibly through
      another domain and TH-dependent down-regulation through the AF-2 domain.

PMID- 19406945
TI  - Metalloproteinase-dependent shedding of low-density lipoprotein receptor-related
      protein-1 ectodomain decreases endocytic clearance of endometrial matrix
      metalloproteinase-2 and -9 at menstruation.
AB  - Cyclic elimination of the endometrium functional layer through menstrual bleeding
      results from intense tissue breakdown by proteolytic enzymes, mainly members of
      the matrix metalloproteinase (MMP) family. In contrast to menstrual-restricted
      MMPs, e.g. interstitial collagenase (MMP-1), gelatinases A (MMP-2) and B (MMP-9)
      mRNAs are abundant throughout the cycle without detectable tissue degradation at
      proliferative and secretory phases, implying a tight posttranslational control of
      both gelatinases. This paper addresses the role of low-density lipoprotein
      receptor-related protein (LRP)-1 in the endocytic clearance of endometrial
      gelatinases. LRP-1 mRNA and protein were studied using RT-PCR, Western blotting,
      and immunolabeling. Posttranslational control of LRP-1 was analyzed in explant
      culture. The receptor-associated protein (RAP), used as LRP antagonist, strongly
      increased (pro)gelatinase accumulation in medium conditioned by endometrial
      explants, suggesting a role for LRP-1 in their clearance. Although LRP-1 mRNA
      remained constant throughout the cycle, the protein ectodomain vanished at
      menses. LRP-1 immunolabeling selectively disappeared in areas of extracellular
      matrix breakdown in menstrual samples. It also disappeared from explants cultured
      without estrogen and progesterone (EP) due to ectodomain shedding in the medium.
      The shedding was inhibited by metalloproteinase inhibitors, including a
      disintegrin and metalloproteinase (ADAM) inhibitor, and by tissue inhibitors of
      MMPs (TIMP)-3 and -2, but barely by TIMP-1, pointing to ADAM-12 as the putative
      sheddase. In good agreement, ADAM-12 mRNA expression was repressed by EP. In
      conclusion, the efficient LRP-1-mediated clearance of gelatinase activity in
      nonbleeding endometrium is abrogated upon EP withdrawal, due to shedding of LRP-1
      ectodomain by a metalloproteinase, presumably ADAM-12, itself regulated by EP.

PMID- 19406946
TI  - In vitro and in vivo effects of adiponectin on bone.
AB  - Fat mass impacts on both bone turnover and bone density and is a critical risk
      factor for osteoporotic fractures. Adipocyte-derived hormones may contribute to
      this relationship, and adiponectin is a principal circulating adipokine. However,
      its effects on bone remain unclear. We have, therefore, investigated the direct
      effects of adiponectin on primary cultures of osteoblastic and osteoclastic cells
      in vitro and determined its integrated effects in vivo by characterizing the bone
      phenotype of adiponectin-deficient mice. Adiponectin was dose-dependently
      mitogenic to primary rat and human osteoblasts ( approximately 50% increase at 10
      microg/ml) and markedly inhibited osteoclastogenesis at concentrations of 1
      microg/ml or greater. It had no effect on osteoclastogenesis in RAW-264.7 cells
      or on bone resorption in isolated mature osteoclasts. In adiponectin knockout
      (AdKO) male C57BL/6J mice, trabecular bone volume and trabecular number (assessed
      by microcomputed tomography) were increased at 14 wk of age by 30% (P = 0.02) and
      38% (P = 0.0009), respectively. Similar, nonsignificant trends were observed at 8
      and 22 wk of age. Biomechanical testing showed lower bone fragility and reduced
      cortical hardness at 14 wk. We conclude that adiponectin stimulates osteoblast
      growth but inhibits osteoclastogenesis, probably via an effect on stromal cells.
      However, the AdKO mouse has increased bone mass, suggesting that adiponectin also
      has indirect effects on bone, possibly through modulating growth factor action or
      insulin sensitivity. Because adiponectin does influence bone mass in vivo, it is
      likely to be a contributor to the fat-bone relationship.

PMID- 19406948
TI  - Caveolin-1 loss of function accelerates glucose transporter 4 and insulin
      receptor degradation in 3T3-L1 adipocytes.
AB  - Caveolae are a specialized type of lipid rafts that are stabilized by oligomers
      of caveolin protein. Caveolae are particularly enriched in adipocytes. Here we
      analyzed the effects of caveolin-1 knockdown and caveolae ablation on adipocyte
      function. To this end, we obtained several multiclonal mouse 3T3-L1 cell lines
      with a reduced expression of caveolin-1 (95% reduction) by a small interfering
      RNA approach using lentiviral vectors. Control cell lines were obtained by
      lentiviral infection with lentiviral vectors encoding appropriate scrambled RNAs.
      Caveolin-1 knockdown adipocytes showed a drastic reduction in the number of
      caveolae (95% decrease) and cholera toxin labeling was reorganized in dynamic
      plasma membrane microdomains. Caveolin-1 depletion caused a specific decrease in
      glucose transporter 4 (GLUT4) and insulin receptor protein levels. This reduction
      was not the result of a generalized defect in adipocyte differentiation or
      altered gene expression but was explained by faster degradation of these
      proteins. Caveolin-1 knockdown adipocytes showed reductions in insulin-stimulated
      glucose transport, insulin-triggered GLUT4 recruitment to the cell surface, and
      insulin receptor activation. In all, our data indicate that caveolin-1 loss of
      function reduces maximal insulin response through lowered stability and
      diminished expression of insulin receptors and GLUT4. We propose that caveolin
      1/caveolae control insulin action in adipose cells.

PMID- 19406947
TI  - Pioglitazone acutely reduces insulin secretion and causes metabolic deceleration
      of the pancreatic beta-cell at submaximal glucose concentrations.
AB  - Thiazolidinediones (TZDs) have beneficial effects on glucose homeostasis via
      enhancement of insulin sensitivity and preservation of beta-cell function. How
      TZDs preserve beta-cells is uncertain, but it might involve direct effects via
      both peroxisome proliferator-activated receptor-gamma-dependent and -independent
      pathways. To gain insight into the independent pathway(s), we assessed the
      effects of short-term (<or=90 min) exposure to pioglitazone (Pio) (10 to 50
      microM) on glucose-induced insulin secretion (GIIS), AMP-activated protein kinase
      (AMPK) activation, and beta-cell metabolism in INS 832/13 beta-cells and rat
      islets. Pio caused a right shift in the dose-dependence of GIIS, such that
      insulin release was reduced at intermediate glucose but unaffected at either
      basal or maximal glucose concentrations. This was associated in INS 832/13 cells
      with alterations in energy metabolism, characterized by reduced glucose
      oxidation, mitochondrial membrane polarization, and ATP levels. Pio caused AMPK
      phosphorylation and its action on GIIS was reversed by the AMPK inhibitor
      compound C. Pio also reduced palmitate esterification into complex lipids and
      inhibited lipolysis. As for insulin secretion, the alterations in beta-cell
      metabolic processes were mostly alleviated at elevated glucose. Similarly, the
      antidiabetic agents and AMPK activators metformin and berberine caused a right
      shift in the dose dependence of GIIS. In conclusion, Pio acutely reduces glucose
      oxidation, energy metabolism, and glycerolipid/fatty acid cycling of the beta
      cell at intermediate glucose concentrations. We suggest that AMPK activation and
      the metabolic deceleration of the beta-cell caused by Pio contribute to its known
      effects to reduce hyperinsulinemia and preserve beta-cell function and act as an
      antidiabetic agent.

PMID- 19406949
TI  - Insulin-like growth factor type 1 receptor and insulin receptor isoform
      expression and signaling in mammary epithelial cells.
AB  - The insulin receptor (IR) isoforms and the IGF type 1 receptor (IGF-1R) share a
      high degree of structural homology but differ in ligand binding kinetics and
      functions. We developed a highly specific quantitative PCR assay to quantify and
      compare IR-A, IR-B, and IGF-1R expression within an RNA population. We determined
      receptor expression in primary murine mammary epithelial cells (MECs) during
      postnatal development. Both IR isoform mRNAs were 3- to 16-fold higher than IGF
      1R expression at all developmental times. IR protein was also 3- to 10-fold
      higher than IGF-1R protein; however, significantly less IGF-1R was found in
      hybrid receptors at early (49%) vs. late (79%) pregnancy, indicating that the
      amount of hybrid receptor is developmentally regulated. Despite high IR
      expression, IGF ligands were more effective than insulin in stimulating the
      insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt pathway in acutely
      isolated MECs from virgin glands. Although approximately 40% of IR transcripts
      were the IGF-II-sensitive IR-A isoform, IGF-II failed to stimulate IR
      phosphorylation, and an IGF-1R-specific blocking antibody completely abrogated
      IGF-II-mediated Akt phosphorylation in the virgin MECs. Taken together, these
      data suggest that the IGF-1R is more active in signaling than the IR and is the
      predominant mediator of IGF actions in virgin MECs.

PMID- 19406951
TI  - Characterizing the effects of common UDP glucuronosyltransferase (UGT) 1A6 and
      UGT1A1 polymorphisms on cis- and trans-resveratrol glucuronidation.
AB  - The dietary polyphenol resveratrol (RES) exists as cis- and trans-isomers with
      known stereospecific and stereoselective glucuronidation at the 3 and 4'
      positions by distinct UGT1A isoforms. We examined cis-RES glucuronidation in
      various protein sources. UGT1A6 or UGT1A1 genotype-dependent cis-or trans-RES
      glucuronidation, respectively, was further determined. cis-RES exhibited partial
      substrate inhibition in UGT1A6 Supersomes and human embryonic kidney 293 cells
      overexpressing genetically variant UGT1A6 alleles. Cells expressing UGT1A6*4 had
      the highest activity with a V(max) of 612 +/- 27.36 nmol/min/mg, followed by
      UGT1A6*3. The *2 allozyme had a higher V(max) (1.6-fold) and K(m) (1.9-fold) than
      *1. In 51 human liver samples genotyped for UGT1A6, four alleles (frequencies)
      were identified as *1 (0.58), *2 (0.36), *3 (0.01), and *4 (0.05), leading to
      assignment of the following genotypes (frequencies): *1/*1 (0.29), *1/*2 (0.45),
      *1/*3 (0.02), *1/*4 (0.10), and *2/*2 (0.14). Up to 5-fold variability in trans
      RES glucuronidation was observed in individual liver samples. In livers
      stratified by UGT1A6 genotype, a significant difference in cis-RES
      glucuronidation activity (p < 0.05) was seen between the *2 variants compared
      with homozygous *1 livers. The trans-RES glucuronidation was quantitated in a
      human liver bank genotyped for the UGT1A1 TATA box repeat polymorphism. There was
      no significant difference for formation of trans-RES 3-O-glucuronide. We were
      surprised to find that trans-RES 4'-O-glucuronide formation was higher in livers
      with the 7/7 genotype compared with 6/6 and 6/7 (p < 0.05). In conclusion, cis
      RES glucuronidation exhibited atypical partial substrate inhibition kinetics in
      vitro. Whereas cis-RES glucuronidation varied with UGT1A6 genotypes, the
      UGT1A1*28 polymorphism did not explain variability in trans-RES glucuronidation.

PMID- 19406950
TI  - Vascular endothelial growth factor receptor 2 (VEGFR-2) functions to promote
      uterine decidual angiogenesis during early pregnancy in the mouse.
AB  - Implantation of an embryo induces rapid proliferation and differentiation of
      uterine stromal cells, forming a new structure, the decidua. One salient feature
      of decidua formation is a marked increase in maternal angiogenesis. Vascular
      endothelial growth factor (VEGF)-dependent pathways are active in the ovary,
      uterus, and embryo, and inactivation of VEGF function in any of these structures
      might prevent normal pregnancy development. We hypothesized that decidual
      angiogenesis is regulated by VEGF acting through specific VEGF receptors
      (VEGFRs). To test this hypothesis, we developed a murine pregnancy model in which
      systemic administration of a receptor-blocking antibody would act specifically on
      uterine angiogenesis and not on ovarian or embryonic angiogenesis. In our model,
      ovarian function was replaced with exogenous progesterone, and blocking
      antibodies were administered prior to embryonic expression of VEGFRs. After
      administration of a single dose of the anti-VEGFR-2 antibody during the peri
      implantation period, no embryos were detected on embryonic d 10.5. The pregnancy
      was disrupted because of a significant reduction in decidual angiogenesis, which
      under physiological conditions peaks on embryonic d 5.5 and 6.5. Inactivation of
      VEGFR-3 reduced angiogenesis in the primary decidual zone, whereas administration
      of VEGFR-1 blocking antibodies had no effect. Pregnancy was not disrupted after
      administration of anti-VEGFR-3 or anti-VEGFR-1 antibodies. Thus, the VEGF/VEGFR-2
      pathway plays a key role in the maintenance of early pregnancy through its
      regulation of peri-implantation angiogenesis in the uterine decidua. This newly
      formed decidual vasculature serves as the first exchange apparatus for the
      developing embryo until the placenta becomes functionally active.

PMID- 19406952
TI  - Cannabidiol-2',6'-dimethyl ether, a cannabidiol derivative, is a highly potent
      and selective 15-lipoxygenase inhibitor.
AB  - The inhibitory effect of nordihydroguaiaretic acid (NDGA) (a nonselective
      lipoxygenase (LOX) inhibitor)-mediated 15-LOX inhibition has been reported to be
      affected by modification of its catechol ring, such as methylation of the
      hydroxyl group. Cannabidiol (CBD), one of the major components of marijuana, is
      known to inhibit LOX activity. Based on the phenomenon observed in NDGA, we
      investigated whether or not methylation of CBD affects its inhibitory potential
      against 15-LOX, because CBD contains a resorcinol ring, which is an isomer of
      catechol. Although CBD inhibited 15-LOX activity with an IC(50) value (50%
      inhibition concentration) of 2.56 microM, its monomethylated and dimethylated
      derivatives, CBD-2'-monomethyl ether and CBD-2',6'-dimethyl ether (CBDD),
      inhibited 15-LOX activity more strongly than CBD. The number of methyl groups in
      the resorcinol moiety of CBD (as a prototype) appears to be a key determinant for
      potency and selectivity in inhibition of 15-LOX. The IC(50) value of 15-LOX
      inhibition by CBDD is 0.28 microM, and the inhibition selectivity for 15-LOX
      (i.e., the 5-LOX/15-LOX ratio of IC(50) values) is more than 700. Among LOX
      isoforms, 15-LOX is known to be able to oxygenate cholesterol esters in the low
      density lipoprotein (LDL) particle (i.e., the formation of oxidized LDL). Thus,
      15-LOX is suggested to be involved in development of atherosclerosis, and CBDD
      may be a useful prototype for producing medicines for atherosclerosis.

PMID- 19406953
TI  - Vitreal kinetics of quinidine in rabbits in the presence of topically
      coadministered P-glycoprotein substrates/modulators.
AB  - The purpose of this study was to investigate whether topically administered P
      glycoprotein (P-gp) substrates/modulators can alter vitreal kinetics of
      intravitreally administered quinidine. Male New Zealand rabbits were used under
      anesthesia. Vitreal kinetics of intravitreally administered quinidine (0.75
      microg dose) was determined alone and in the presence of verapamil
      (coadministered topically/intravitreally) or prednisolone hemisuccinate sodium
      (PHS) (coadministered topically). In the presence of topically instilled
      verapamil (1% w/v), elimination half-life (t(1/2)) (176 +/- 7 min), apparent
      elimination rate constant (lambda(z)) (0.0039 +/- 0.0001 min(-1)), and mean
      retention time (MRT) (143 +/- 30 min) of intravitreally administered quinidine
      were significantly different from those of the control (105 +/- 11 min, 0.0066 +/
      0.0007 min(-1), and 83 +/- 13 min, respectively). A 2-fold increase in the
      t(1/2) with a corresponding decrease in lambda(z) and a 1.5-fold increase in the
      MRT of quinidine were observed in the presence of topically coadministered 2% w/v
      PHS. Intravitreal coadministration of quinidine and verapamil resulted in a
      significant increase in t(1/2) (159 +/- 9 min) and a decrease in lambda(z)
      (0.0043 +/- 0.0002 min(-1)) of quinidine. The vitreal pharmacokinetic parameters
      of sodium fluorescein, alone or in the presence of topically instilled verapamil,
      did not show any statistically significant difference, indicating that ocular
      barrier integrity was not affected by topical verapamil administration. Results
      from this study suggest that topically applied P-gp substrates/modulators can
      alter vitreal pharmacokinetics of intravitreally administered P-gp substrates,
      possibly through the inhibition of P-gp expressed on the basolateral membrane of
      the retinal pigmented epithelium.

PMID- 19406954
TI  - Comparison of different algorithms for predicting clinical drug-drug
      interactions, based on the use of CYP3A4 in vitro data: predictions of compounds
      as precipitants of interaction.
AB  - Cytochrome P450 3A4 (CYP3A4) is the most important enzyme in drug metabolism and
      because it is the most frequent target for pharmacokinetic drug-drug interactions
      (DDIs) it is highly desirable to be able to predict CYP3A4-based DDIs from in
      vitro data. In this study, the prediction of clinical DDIs for 30 drugs on the
      pharmacokinetics of midazolam, a probe substrate for CYP3A4, was done using in
      vitro inhibition, inactivation, and induction data. Two DDI prediction approaches
      were used, which account for effects at both the liver and intestine. The first
      was a model that simultaneously combines reversible inhibition, time-dependent
      inactivation, and induction data with static estimates of relevant in vivo
      concentrations of the precipitant drug to provide point estimates of the average
      magnitude of change in midazolam exposure. This model yielded a success rate of
      88% in discerning DDIs with a mean -fold error of 1.74. The second model was a
      computational physiologically based pharmacokinetic model that uses dynamic
      estimates of in vivo concentrations of the precipitant drug and accounts for
      interindividual variability among the population (Simcyp). This model yielded
      success rates of 88 and 90% (for "steady-state" and "time-based" approaches,
      respectively) and mean -fold errors of 1.59 and 1.47. From these findings it can
      be concluded that in vivo DDIs for CYP3A4 can be predicted from in vitro data,
      even when more than one biochemical phenomenon occurs simultaneously.

PMID- 19406956
TI  - Comment on "higher serum creatinine concentrations in black patients with chronic
      kidney disease: beyond nutritional status and body composition".

PMID- 19406955
TI  - Acute or chronic stress induce cell compartment-specific phosphorylation of
      glucocorticoid receptor and alter its transcriptional activity in Wistar rat
      brain.
AB  - Chronic stress and impaired glucocorticoid receptor (GR) feedback are important
      factors for the compromised hypothalamic-pituitary-adrenal (HPA) axis activity.
      We investigated the effects of chronic 21 day isolation of Wistar rats on the
      extrinsic negative feedback part of HPA axis: hippocampus (HIPPO) and prefrontal
      cortex (PFC). In addition to serum corticosterone (CORT), we followed GR
      subcellular localization, GR phosphorylation at serine 232 and serine 246,
      expression of GR regulated genes: GR, CRF and brain-derived neurotropic factor
      (BDNF), and activity of c-Jun N-terminal kinase (JNK) and Cdk5 kinases that
      phosphorylate GR. These parameters were also determined in animals subjected to
      acute 30 min immobilization, which was taken as 'normal' adaptive response to
      stress. In isolated animals, we found decreased CORT, whereas in animals exposed
      to acute immobilization, CORT was markedly increased. Even though the GR was
      predominantly localized in the nucleus of HIPPO and PFC in acute, but not in
      chronic stress, the expression of GR, CRF, and BDNF genes was similarly regulated
      under both acute and chronic stresses. Thus, the transcriptional activity of GR
      under chronic isolation did not seem to be exclusively dependent on high serum
      CORT levels nor on the subcellular location of the GR protein. Rather, it
      resulted from the increased Cdk5 activation and phosphorylation of the nuclear GR
      at serine 232 and the decreased JNK activity reflected in decreased
      phosphorylation of the nuclear GR at serine 246. Our study suggests that this
      nuclear isoform of hippocampal and cortical GR may be related to hypocorticism
      i.e. HPA axis hypoactivity under chronic isolation stress.

PMID- 19406957
TI  - Hepcidin--a potential novel biomarker for iron status in chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Hepcidin is a key regulator of iron homeostasis, but
      its study in the setting of chronic kidney disease (CKD) has been hampered by the
      lack of validated serum assays. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      This study reports the first measurements of bioactive serum hepcidin using a
      novel competitive ELISA in 48 pediatric (PCKD2-4) and 32 adult (ACKD2-4) patients
      with stages 2 to 4 CKD along with 26 pediatric patients with stage 5 CKD (PCKD5D)
      on peritoneal dialysis. RESULTS: When compared with their respective controls
      (pediatric median = 25.3 ng/ml, adult = 72.9 ng/ml), hepcidin was significantly
      increased in PCKD2-4 (127.3 ng/ml), ACKD2-4 (269.9 ng/ml), and PCKD5D (652.4
      ng/ml). Multivariate regression analysis was used to assess the relationship
      between hepcidin and indicators of anemia, iron status, inflammation, and renal
      function. In PCKD2-4 (R(2) = 0.57), only ferritin correlated with hepcidin. In
      ACKD2-4 (R(2) = 0.78), ferritin and soluble transferrin receptor were associated
      with hepcidin, whereas GFR was inversely correlated. In PCKD5D (R(2) = 0.52),
      percent iron saturation and ferritin were predictors of hepcidin. In a
      multivariate analysis that incorporated all three groups (R(2) = 0.6), hepcidin
      was predicted by ferritin, C-reactive protein, and whether the patient had stage
      5D versus stages 2 to 4 CKD. CONCLUSIONS: These findings suggest that increased
      hepcidin across the spectrum of CKD may contribute to abnormal iron regulation
      and erythropoiesis and may be a novel biomarker of iron status and erythropoietin
      resistance.

PMID- 19406958
TI  - In crescentic IgA nephropathy, fractional excretion of IgG in combination with
      nephron loss is the best predictor of progression and responsiveness to
      immunosuppression.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the relationship
      between proteinuric markers (urinary excretion of IgG, alpha2-macroglobulin,
      alpha1-microglobulin) and serum creatinine (sCr), histologic lesions,
      progression, and immunosuppression responsiveness in crescentic IgA nephropathy.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fractional excretion of IgG
      (FEIgG) and of alpha1-microglobulin and urinary excretion of alpha2-macroglobulin
      were evaluated in 37 patients, 23 treated with steroids and cyclophosphamide. For
      assessment of the effective tubular load of proteins in surviving nephrons, new
      markers that take into account not only the absolute excretion value but also
      nephron loss were obtained dividing proteinuric markers for percentage of
      nonobsolescent glomeruli (surviving glomeruli [SG]). For each parameter, low- and
      high-risk groups were defined according to cutoffs with the highest sensitivity
      and specificity for progression (ESRD/doubling sCr) assessed by receiver
      operating characteristic analysis; follow up was 60 +/- 40 mo. RESULTS: FEIgG/SG
      is the most powerful progression predictor: 5 versus 83% in all patients; in
      treated patients, 0 versus 89%, increased to 0 versus 100% by sCr and FEIgG/SG in
      combination (low risk: both markers or only one below cutoff (n = 15); high risk:
      both markers above cutoff (n = 8). The nonprogressors showed at last observation
      65% proteinuria reduction and 10% sCr reduction. CONCLUSIONS: In crescentic IgA
      nephropathy, FEIgG/SG, which evaluates altered size selectivity in relation to
      nephron loss, is the best progression predictor. In treated patients, progression
      prediction was increased by FEIgG/SG and sCr in combination. Treatment may be
      restricted to low-risk patients.

PMID- 19406959
TI  - Nonrecovery of kidney function and death after acute on chronic renal failure.
AB  - BACKGROUND AND OBJECTIVES: Relatively little is known about clinical outcomes,
      especially long-term outcomes, among patients who have chronic kidney disease
      (CKD) and experience superimposed acute renal failure (ARF; acute on chronic
      renal failure). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We tracked 39,805
      members of an integrated health care delivery system in northern California who
      were hospitalized during 1996 through 2003 and had prehospitalization estimated
      GFR (eGFR) <45 ml/min per 1.73 m(2). Superimposed ARF was defined as having both
      a peak inpatient serum creatinine greater than the last outpatient serum
      creatinine by > or =50% and receipt of acute dialysis. RESULTS: Overall, 26% of
      CKD patients who suffered superimposed ARF died during the index hospitalization.
      There was a high risk for developing ESRD within 30 d of hospital discharge that
      varied with preadmission renal function, being 42% among hospital survivors with
      baseline eGFR 30-44 ml/min per 1.73 m(2) and 63% among hospital survivors with
      baseline eGFR 15-29 ml/min per 1.73 m(2). Compared with patients who had CKD and
      did not experience superimposed ARF, those who did had a 30% higher long-term
      risk for death or ESRD. CONCLUSIONS: In a large, community-based cohort of
      patients with CKD, an episode of superimposed dialysis-requiring ARF was
      associated with very high risk for nonrecovery of renal function. Dialysis
      requiring ARF also seemed to be an independent risk factor for long-term risk for
      death or ESRD.

PMID- 19406960
TI  - Estimating glomerular filtration rate: Cockcroft-Gault and Modification of Diet
      in Renal Disease formulas compared to renal inulin clearance.
AB  - BACKGROUND AND OBJECTIVES: Evaluation of renal function by estimation of the
      glomerular filtration rate (GFR) is very important for the diagnosis and
      treatment of patients with chronic kidney disease (CKD). The Cockcroft-Gault (CG)
      and Modification of Diet in Renal Disease (MDRD) formulas are the most commonly
      used estimations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Estimated GFR
      values by each formula were compared with measured GFR (mGFR) by renal inulin
      clearance in 2208 European adults (46% women, 1.4% Caribbean blacks), with and
      without CKD, and mean mGFR 72.4 +/- 39.0 (range 2.2 to 177.2) ml/min/1.73 m(2).
      RESULTS: Overall, the CG and MDRD formulas showed bias (mean difference) -3.5
      ml/min/1.73 m(2) (5.3%), P < 0.001, and -9.8 ml/min/1.73 m(2) (-6.4%), P < 0.001;
      precision (SD of bias) 21.5 ml/min/1.73 m(2) (43.1%) and 20.0 ml/min/1.73 m(2)
      (33.0%); limits of agreement (2 SD by Bland-Altman method) 39.5 to -46.5 (range
      86.0) ml/min/1.73 m(2) and 30.2 to -49.8 (range 80.0) ml/min/1.73 m(2); and
      accuracy within +/-30% of mGFR 70.8 and 69.0%, respectively. Both formulas showed
      a trend for decreasing accuracy with lower mGFR levels. According to the Kidney
      Disease Outcomes Quality Initiative (K/DOQI)-CKD classification's five GFR
      groups, the CG and MDRD formulas properly assigned 61.6 and 57.1% of the entire
      population and had a range of positive predictive values 42.6 to 81.8% and 39.6
      to 85.2% and of negative predictive values 81.7 to 96.6% and 76.4 to 97.5%,
      respectively. CONCLUSIONS: The CG and MDRD formulas had some limitations for
      proper GFR estimation and K/DOQI-CKD classification by GFR levels alone.

PMID- 19406961
TI  - Twelve-month pancreas graft function significantly influences survival following
      simultaneous pancreas-kidney transplantation.
AB  - BACKGROUND AND OBJECTIVES: Simultaneous pancreas-kidney transplantation (SPK) is
      regarded as the treatment of choice for type 1 diabetes (T1DM) and kidney
      dysfunction, despite the morbidity associated with pancreas transplantation.
      These morbidities often influence selection of SPK versus living-donor kidney
      alone (LD KA) transplant. This study quantifies the impact of pancreas graft
      function on outcomes following SPK. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Using the SRTR database, SPK wait-listed patients transplanted from
      1997 to 2005 were evaluated and segregated as: (1) SPK recipients with
      functioning pancreas graft 12 mo posttransplant (SPK, P+); (2) SPK recipients
      with loss of pancreas graft function within 12 mo posttransplant (SPK, P-); (3)
      recipients of deceased donor (DD) KA; (4) recipients of LD KA. The study compared
      patient and kidney graft survival to 84 mo posttransplant. RESULTS: Patient
      survival for SPK, P+ was significantly better than the LD KA; SPK, P-; and DD KA
      cohorts (88.6% versus 80.0%, 73.9% and 64.8%, respectively [P < 0.001]), a
      finding confirmed by multivariate analysis and not influenced by pancreas-after
      kidney transplantation (PAK) rates and outcomes. Unadjusted graft survival was
      also highest in the SPK, P+ cohort (72.0% versus 63.6%, 59.8%, 49.7%, P = 0.015
      versus LD KA). CONCLUSIONS: SPK recipients with functioning pancreas grafts have
      superior survival compared with LD KA and DD KA, including in the setting of PAK.
      Early pancreas graft failure results in kidney and patient survival rates similar
      to KA. These data help further clarify the decision-making of SPK versus KA
      transplant options for patients and providers.

PMID- 19406962
TI  - Urinary biomarkers in the early detection of acute kidney injury after cardiac
      surgery.
AB  - BACKGROUND AND OBJECTIVES: Serum creatinine (Scr) does not allow for early
      diagnosis of acute kidney injury (AKI). The diagnostic utility of urinary kidney
      injury molecule-1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG), and neutrophil
      gelatinase associated lipocalin (NGAL) was evaluated for the early detection of
      postoperative AKI in a prospective study of 90 adults undergoing cardiac surgery.
      Designs, setting, participants, & measurements: Urinary KIM-1, NAG, and NGAL were
      measured at 5 time points for the first 24 h after operation and normalized to
      the urinary creatinine concentration after cardiac surgery. Receiver-operating
      characteristic curves were generated and the areas under the curve (AUCs)
      compared for performance of biomarkers in detection of postoperative AKI.
      RESULTS: Thirty-six patients developed AKI, defined as an increase in Scr of > or
      =0.3 mg/dl within 72 h after surgery. The AUCs for KIM-1 to predict AKI
      immediately and 3 h after operation were 0.68 and 0.65; 0.61 and 0.63 for NAG;
      and 0.59 and 0.65 for NGAL, respectively. Combining the three biomarkers enhanced
      the sensitivity of early detection of postoperative AKI compared with individual
      biomarkers: the AUCs for the three biomarkers combined were 0.75 and 0.78. The
      performance of combining biomarkers was even better among 16 early postoperative
      AKI patients with AUCs of 0.80 and 0.84, respectively. CONCLUSIONS: The results
      of this study support that a combination of urinary biomarkers may allow for
      early detection of postoperative AKI after cardiac surgery before a rise in Scr.

PMID- 19406963
TI  - Treatment of severe edema in children with nephrotic syndrome with diuretics
      alone--a prospective study.
AB  - BACKGROUND AND OBJECTIVE: Severe edema in children with nephrotic syndrome (NS)
      may be associated with volume contraction (VC) or volume expansion (VE). Usually,
      severe edema in children is treated with intravenous (IV) albumin and diuretics,
      which is appropriate for VC patients. However, in VE patients, this can
      precipitate fluid overload. The objective of this study was to evaluate treatment
      of severe edema in NS with diuretics alone. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Thirty NS patients with severe edema were enrolled in this
      prospective study in two phases. VC was diagnosed based on fractional excretion
      of sodium (FeNa) <1%. VC patients received IV albumin and furosemide. VE patients
      received IV furosemide and oral spironolactone. On the basis of phase 1
      observations, FeNa <0.2% identified VC in 20 phase 2 patients. RESULTS: All phase
      1 patients had FeNa <1%. Phase 1 patients when reanalyzed based on a FeNa cutoff
      of 0.2%; it was noted that VC patients had higher BUN, BUN/creatinine ratio,
      urine osmolality, and lower FeNa and urine sodium compared with VE patients.
      Similar results were observed in phase 2. VC patients had significantly higher
      renin, aldosterone, and antidiuretic hormone levels. In phase 2, 11 VE patients
      received diuretics alone and 9 VC patients received albumin and furosemide. There
      was no difference in hospital stay and weight loss in VC and VE groups after
      treatment. CONCLUSIONS: FeNa is useful in distinguishing VC versus VE in NS
      children with severe edema. The use of diuretics alone in VE patients is safe and
      effective.

PMID- 19406965
TI  - Stent placement in hemodialysis access: historical lessons, the state of the art
      and future directions.
AB  - Vascular access stenosis in patients undergoing chronic hemodialysis is a major
      issue that is associated with increased morbidity, mortality, and cost of medical
      care. Recent data have emphasized that endovascular stents could be used in the
      treatment of central as well as peripheral stenotic lesions. In general, a
      peripheral or central vein lesion that is elastic or recurs within a three-month
      period after an initially successful balloon angioplasty or a stenosis where
      surgical revision is not possible are some indications for intravascular stent
      placement. Recent reports have expanded the role of stents in the management of
      pseudoaneurysms associated with dialysis access. In this context, the utilization
      of these devices must take into account a fair comparison with the traditional
      (surgical) approaches regarding effectiveness as well as costs. This report
      describes the role of stents in arteriovenous dialysis access. In addition, some
      of the recent advances in the structure and complicating issues such as stent
      fracture, migration, and infection, as well cannulation through the stent, are
      discussed.

PMID- 19406964
TI  - Association of genetic variants with chronic kidney disease in Japanese
      individuals.
AB  - BACKGROUND AND OBJECTIVES: Although genetic linkage analyses and association
      studies have implicated several loci and candidate genes in predisposition to
      chronic kidney disease (CKD), the genes that underlie genetic susceptibility to
      this condition have remained uncharacterized. The purpose of the present study
      was to identify genetic variants that confer susceptibility to CKD in Japanese
      individuals. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study population
      comprised 5217 Japanese individuals (2955 men, 2262 women), including 778
      subjects (480 men, 298 women) with CKD [estimated GFR (eGFR), <50 ml min(-1) 1.73
      m(-2)] and 4439 controls (2475 men, 1964 women; eGFR, > or =60 ml min(-1) 1.73 m(
      2)). The genotypes for 40 polymorphisms of 32 candidate genes were determined.
      RESULTS: The chi-square test and multivariable logistic regression analysis with
      adjustment for covariates revealed that the -219G-->T polymorphism of APOE, the 
      519A-->G of MMP1, the -866G-->A of UCP2, the -1607/1G-->2G of MMP1, the A-->G
      (Lys45Glu) of MMP3, the G-->A (Ala163Thr) of AGTR1, the G-->A (Gly670Arg) of
      PECAM1, and the -55C-->T of UCP3 were significantly (false discovery rate <0.05)
      associated with CKD. Comparison of allele frequencies of these polymorphisms by
      the chi-square test between subgroups of CKD and control subjects individually
      matched for covariates revealed that the -519A-->G of MMP1 and the -866G-->A of
      UCP2 were significantly (P < 0.05) associated with CKD. CONCLUSIONS: MMP1 and
      UCP2 may be susceptibility loci for CKD in Japanese individuals. Determination of
      genotypes for these polymorphisms may prove informative for prediction of genetic
      risk for CKD.

PMID- 19406968
TI  - Clinical outcomes of dialysis catheter-related candidemia in hemodialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: Candidemia is a rare complication in catheter
      dependent hemodialysis patients. As a result, there is uncertainty about its
      optimal medical management. The goal of this retrospective study was to compare
      the clinical outcomes of catheter-related candidemia managed with two different
      strategies: Guidewire exchange of the infected catheter versus removal with
      delayed replacement. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      retrospectively queried a prospective, computerized vascular access database to
      identify 40 hemodialysis patients with catheter-related candidemia. All patients
      underwent treatment with antifungal medications for 2 wk, in conjunction with
      guidewire catheter exchange or catheter removal with delayed replacement. The
      primary outcomes were major complications, recurrent candidemia, and patient
      survival. RESULTS: Candidemia represented approximately 2% of all cases of
      catheter-related bloodstream infections. Of the 40 patients with candidemia, 27
      underwent guidewire catheter exchange and 13 had prompt catheter removal with
      delayed replacement. The two treatment groups were similar in demographic,
      clinical, and catheter characteristics. Only 1 (2.5%) patient developed a serious
      complication (endophthalmitis). Recurrence of candidemia within 3 mo was observed
      in 15% of each treatment group. Patient survival at 6 mo was similar in both
      groups. CONCLUSIONS: Catheter-related candidemia is rare in hemodialysis patients
      and has a low complication rate. Catheter exchange over a guidewire in
      conjunction with antifungal therapy is an effective and safe treatment regimen.

PMID- 19406966
TI  - Clinical features and long-term outcome of nephrotic syndrome associated with
      heterozygous NPHS1 and NPHS2 mutations.
AB  - BACKGROUND AND OBJECTIVES: Mutations in nephrin (NPHS1) and podocin (NPHS2) genes
      represent a major cause of idiopathic nephrotic syndrome (NS) in children. It is
      not yet clear whether the presence of a single mutation acts as a modifier of the
      clinical course of NS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We reviewed
      the clinical features of 40 patients with NS associated with heterozygous
      mutations or variants in NPHS1 (n = 7) or NPHS2 (n = 33). Long-term renal
      survival probabilities were compared with those of a concurrent cohort with
      idiopathic NS. RESULTS: Patients with a single mutation in NPHS1 received a
      diagnosis before those with potentially nongenetic NS and had a good response to
      therapies. Renal function was normal in all cases. For NPHS2, six patients had
      single heterozygous mutations, six had a p.P20L variant, and 21 had a p.R229Q
      variant. Age at diagnosis and the response to drugs were comparable in all NS
      subgroups. Overall, they had similar renal survival probabilities as non
      NPHS1/NPHS2 cases (log-rank chi(2) 0.84, P = 0.656) that decreased in presence of
      resistance to therapy (P < 0.001) and in cases with renal lesions of
      glomerulosclerosis and IgM deposition (P < 0.001). Cox regression confirmed that
      the only significant predictor of dialysis was resistance to therapy.
      CONCLUSIONS: Our data indicate that single mutation or variant in NPHS1 and NPHS2
      does not modify the outcome of primary NS. These patients should be treated
      following consolidated schemes and have good chances for a good long-term
      outcome.

PMID- 19406969
TI  - Predictors of peritonitis in patients on peritoneal dialysis: results of a large,
      prospective Canadian database.
AB  - BACKGROUND AND OBJECTIVES: Despite the decreasing incidence of peritonitis among
      peritoneal dialysis (PD) patients over time, its occurrence is still associated
      with significant morbidity and mortality. Determining factors that are associated
      with PD peritonitis may facilitate the identification of patients who are at
      risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data collected in the
      multicenter Baxter POET database between 1996 and 2005, the study population
      included incident Canadian PD patients. Potential predictors of peritonitis were
      sought using a negative binomial model and an Andersen-Gill model. Study
      variables included age, gender, race, cause of renal disease, diabetes status,
      transfer from hemodialysis (HD), previous renal transplant, and continuous
      ambulatory PD (CAPD) versus automated PD (APD). RESULTS: Data were available for
      4247 incident PD patients, including 1605 patients with a total of 2555
      peritonitis episodes. Using the negative binomial regression model, factors that
      were independently associated with a higher peritonitis rate included age, Black
      race, and having transferred from HD. There was an interaction between gender and
      diabetes, with an increased risk for peritonitis among female patients with
      diabetes. The use of CAPD versus APD did not affect the peritonitis rate. The
      Andersen-Gill model for recurrent events yielded similar results. CONCLUSIONS:
      Predictors of PD peritonitis included Black race, transferring from HD to PD, and
      diabetes among women. In contrast to previous findings, CAPD and APD were similar
      with regard to peritonitis risk.

PMID- 19406970
TI  - Renal involvement in cystic fibrosis: diseases spectrum and clinical relevance.
AB  - BACKGROUND AND OBJECTIVES: Clinically relevant kidney involvement is uncommonly
      described in adult patients with cystic fibrosis (CF). We sought to report on a
      series of patients with CF and kidney biopsy-documented renal involvement.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective study was
      undertaken in two referral centers for adult patients with CF in Paris, France.
      Patients who had undergone a biopsy of native kidneys between 1992 and 2008 were
      identified, and their medical records were reviewed. RESULTS: We identified 13
      adult patients with CF and renal disease. Proteinuria was present in all but two
      cases and was associated with progressive renal impairment in four patients
      (median serum creatinine 85 micromol/L; range 53 to 144 micromol/L). Renal biopsy
      disclosed a heterogeneous spectrum of nephropathies including AA amyloidosis (n =
      3), diabetic glomerulopathy (n = 3), FSGS (n = 2), minimal-change disease (n =
      1), postinfectious glomerulonephritis (n = 1), IgA nephropathy related to Henoch
      Schonlein purpura (n = 1), membranous nephropathy (n = 1), and chronic
      interstitial nephropathy (n = 1). Chronic renal failure occurred in five
      patients, and one patient reached ESRD. CONCLUSIONS: Although rare, clinically
      significant renal disease may arise in young adult patients with CF. Given the
      wide spectrum of diseases that may be encountered, definite diagnosis by kidney
      biopsy is mandatory to optimize clinical treatment of these complex patients,
      particularly in the perspective of organ transplantation.

PMID- 19406971
TI  - Comparison of volume overload with cycler-assisted versus continuous ambulatory
      peritoneal dialysis.
AB  - BACKGROUND AND OBJECTIVES: Cycler-assisted peritoneal dialysis (CCPD) has been
      associated with decreased sodium removal compared with continuous ambulatory
      peritoneal dialysis (CAPD) as a result of peritoneal sodium sieving during the
      short dwells that are associated with CCPD. This may have adverse consequences
      for management of extracellular fluid volume (ECFV). This study compared ECFV in
      patients who received CAPD or CCPD; CCPD dwell times were maximized by limiting
      the number of exchanges, and the use of icodextrin for the long daytime dwells
      was widespread. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was an
      observational, cross-sectional study of 158 prevalent patients (90 CAPD, 68
      CCPD). Demographic data, blood work, and 24-h dialysate and urine samples were
      collected from all participants between January 2004 and July 2006. They
      subsequently underwent assessment of ECFV by multifrequency bioimpedance
      spectroscopy analysis. Multivariate analysis was used to determine the
      relationship between peritoneal dialysis modality and ECFV. Potential cofounders
      including age, comorbidity, time on dialysis, residual renal function, and
      icodextrin use were identified a priori. RESULTS: There were no differences in
      BP, use of antihypertensive medications, or the presence of peripheral edema
      between CAPD and CCPD patients. Similarly, there was no difference in the ratio
      of ECFV to total body water between CAPD (51.8%) and CCPD (51.9%) patients (P =
      0.929). CONCLUSIONS: There is no difference in BP, sodium removal, or volume
      control in patients who use a contemporary approach to CCPD that uses fewer night
      cycles and liberalizes the use of icodextrin when compared with CAPD.

PMID- 19406973
TI  - Incidence and risk factors associated with hip fracture in institutionalised
      elderly people in Japan.

PMID- 19406972
TI  - Pseudomonas peritonitis in Australia: predictors, treatment, and outcomes in 191
      cases.
AB  - BACKGROUND AND OBJECTIVES: Pseudomonas peritonitis is a serious complication of
      peritoneal dialysis. To date, there as been no comprehensive, multicenter study
      of this condition. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The predictors,
      treatment, and clinical outcomes of Pseudomonas peritonitis were examined by
      binary logistic regression and multilevel, multivariate Poisson regression in all
      Australian PD patients in 66 centers between 2003 and 2006. RESULTS: A total of
      191 episodes of Pseudomonas peritonitis (5.3% of all peritonitis episodes)
      occurred in 171 individuals. Its occurrence was independently predicted by
      Maori/Pacific Islander race, Aboriginal/Torres Strait Islander race, and absence
      of baseline peritoneal equilibration test data. Compared with other organisms,
      Pseudomonas peritonitis was associated with greater frequencies of
      hospitalization (96 versus 79%; P = 0.006), catheter removal (44 versus 20%; P <
      0.001), and permanent hemodialysis transfer (35 versus 17%; P < 0.001) but
      comparable death rates (3 versus 2%; P = 0.4). Initial empiric antibiotic choice
      did not influence outcomes, but subsequent use of dual anti-pseudomonal therapy
      was associated with a lower risk for permanent hemodialysis transfer (10 versus
      38%, respectively; P = 0.03). Catheter removal was associated with a lower risk
      for death than treatment with antibiotics alone (0 versus 6%; P < 0.05).
      CONCLUSIONS: Pseudomonas peritonitis is associated with high rates of catheter
      removal and permanent hemodialysis transfer. Prompt catheter removal and use of
      two anti-pseudomonal antibiotics are associated with better outcomes.

PMID- 19406974
TI  - Risk factors for hip fracture among institutionalised older people.
AB  - BACKGROUND: risk factors for hip fracture in community-dwelling individuals have
      been extensively studied, but there have been fewer studies of institutionalised
      older people. METHODS: a total of 1,894 older people (1,433 females, 461 males;
      mean age 86 years, SD 7.1 years) were recruited from 52 nursing homes and 30
      intermediate-care nursing care facilities in Australia during March 1999 and
      February 2003. We assessed clinical risk factors for hip fracture and skeletal
      fragility by calcaneus broadband ultrasound attenuation (BUA) at baseline and
      then followed up for fracture for 4 years. Hip fractures were validated by x-ray
      reports. Survival analysis with age as a time-dependent covariate was used to
      analyse the data. RESULTS: during a mean follow-up period of 2.65 years (SD
      1.38), 201 hip fractures in 191 residents were recorded, giving an overall hip
      fracture incidence rate of 4.0% per person year (males 3.6% and females 4.1%).
      Residents living in intermediate-care hostels had a higher crude hip fracture
      rate (4.6% vs. 3.0%) than those living in high-care nursing homes. In
      multivariate analysis, an increased risk of hip fracture was significantly
      associated with older age, cognitive impairment, a history of fracture since age
      50, lower body weight, longer lower leg length and poorer balance in intermediate
      care hostel residents, but not with lower BUA. CONCLUSIONS: institutionalised
      older people, who are at a higher risk of hip fracture than community-dwelling
      individuals, have differences in some risk factors for hip fracture that should
      be considered in targeting intervention programs.

PMID- 19406975
TI  - The rapid development of hyponatraemia and seizures in an elderly patient
      following sodium picosulfate/magnesium citrate (Picolax).

PMID- 19406976
TI  - Dietary phosphorus acutely impairs endothelial function.
AB  - Excessive dietary phosphorus may increase cardiovascular risk in healthy
      individuals as well as in patients with chronic kidney disease, but the
      mechanisms underlying this risk are not completely understood. To determine
      whether postprandial hyperphosphatemia may promote endothelial dysfunction, we
      investigated the acute effect of phosphorus loading on endothelial function in
      vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load
      increased production of reactive oxygen species, which depended on phosphorus
      influx via sodium-dependent phosphate transporters, and decreased nitric oxide
      production via inhibitory phosphorylation of endothelial nitric oxide synthase.
      Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic
      rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200
      mg of phosphorus in a double-blind crossover study and measured flow-mediated
      dilation of the brachial artery before and 2 h after the meals. The high dietary
      phosphorus load increased serum phosphorus at 2 h and significantly decreased
      flow-mediated dilation. Flow-mediated dilation correlated inversely with serum
      phosphorus. Taken together, these findings suggest that endothelial dysfunction
      mediated by acute postprandial hyperphosphatemia may contribute to the
      relationship between serum phosphorus level and the risk for cardiovascular
      morbidity and mortality.

PMID- 19406977
TI  - Association of CKD and cancer risk in older people.
AB  - People with ESRD are at increased risk for cancer, but it is uncertain when this
      increased risk begins in the spectrum of chronic kidney disease (CKD). The aim of
      our study was to determine whether moderate CKD increases the risk for cancer
      among older people. We linked the Blue Mountains Eye Study, a prospective
      population-based cohort study of 3654 residents aged 49 to 97 yr, and the New
      South Wales Cancer Registry. During a mean follow-up of 10.1 yr, 711 (19.5%)
      cancers occurred in 3654 participants. Men but not women with at least stage 3
      CKD had a significantly increased risk for cancer (test of interaction for gender
      P = 0.004). For men, the excess risk began at an estimated GFR (eGFR) of 55
      ml/min per 1.73 m2 (adjusted hazard ratio [HR] 1.39; 95% confidence interval [CI]
      1.00 to 1.92) and increased linearly as GFR declined. For every 10-ml/min
      decrement in eGFR, the risk for cancer increased by 29% (adjusted HR 1.29; 95% CI
      1.10 to 1.53), with the greatest risk at an eGFR <40 ml/min per 1.73 m2 (adjusted
      HR 3.01; 95% CI 1.72 to 5.27). The risk for lung and urinary tract cancers but
      not prostate was higher among men with CKD. In conclusion, moderate CKD (stage 3)
      may be an independent risk factor for the development of cancer among older men
      but not women, and the effect of CKD on risk may vary for different types of
      cancer.

PMID- 19406978
TI  - Decreased catecholamine degradation associates with shock and kidney injury after
      cardiac surgery.
AB  - Enzymatic pathways involving catechol-O-methyltransferase (COMT) catabolize
      circulating catecholamines. A G-to-A polymorphism in the fourth exon of the COMT
      gene results in a valine-to-methionine amino acid substitution at codon 158,
      which leads to thermolability and low ("L"), as opposed to high ("H"), enzymatic
      activity. We enrolled 260 patients postbypass surgery to test the hypothesis that
      COMT gene variants impair circulating catecholamine metabolism, predisposing to
      shock and acute kidney injury (AKI) after cardiac surgery. In accordance with the
      Hardy-Weinberg equilibrium, we identified 64 (24.6%) homozygous (LL), 123 (47.3%)
      heterozygous (HL), and 73 (28.1%) homozygous (HH) patients. Postoperative
      catecholamines were higher in homozygous LL patients compared with heterozygous
      HL and homozygous HH patients (P < 0.01). During their intensive care stay, LL
      patients had both a significantly greater frequency of vasodilatory shock (LL:
      69%, HL: 57%, HH: 47%; P = 0.033) and a significantly longer median duration of
      shock (LL: 18.5 h, HL: 14.0 h, HH: 11.0 h; P = 0.013). LL patients also had a
      greater frequency of AKI (LL: 31%, HL: 19.5%, HH: 13.7%; P = 0.038) and their AKI
      was more severe as defined by a need for renal replacement therapy (LL: 7.8%, HL:
      2.4%, HH: 0%; P = 0.026). The LL genotype associated with intensive care and
      hospital length of stay (P < 0.001 and P = 0.002, respectively), and we observed
      a trend for higher mortality. Cross-validation analysis revealed a similar graded
      relationship of adverse outcomes by genotype. In summary, this study identifies
      COMT LL homozygosity as an independent risk factor for shock, AKI, and hospital
      stay after cardiac surgery. (ClinicalTrials.gov number, NCT00334009).

PMID- 19406979
TI  - Oxidized LDL modulates apoptosis of regulatory T cells in patients with ESRD.
AB  - Increased levels of oxidized low-density lipoproteins (oxLDL) contribute to the
      increased risk for atherosclerosis, which persists even after adjusting for
      traditional risk factors, among patients with ESRD. Regulatory T cells
      (CD4+/CD25+ Tregs), which down-regulate T cell responses to foreign and self
      antigens, are protective in murine atherogenesis, but whether similar
      immunoregulation occurs in humans with ESRD is unknown. Because cellular defense
      systems against oxLDL involve proteolytic degradation, the authors investigated
      the role of oxLDL on proteasome activity of CD4+/CD25+ Tregs in patients with
      ESRD. CD4+/CD25+ Tregs isolated from uremic patients' peripheral blood,
      especially that of chronically hemodialyzed patients, failed to suppress cell
      proliferation, exhibited cell-cycle arrest, and entered apoptosis by altering
      proteasome activity. Treating CD4+/CD25+ Tregs with oxLDL or uremic serum ex vivo
      decreased the number and suppressive capacity of CD4+/CD25+ Tregs. In vitro,
      oxLDL promoted the accumulation of p27Kip1, the cyclin-dependent kinase inhibitor
      responsible for G1 cell cycle arrest, and increased apoptosis in a time- and
      concentration-dependent manner. In summary, proteasome inhibition by oxLDL leads
      to cell cycle arrest and apoptosis, dramatically affecting the number and
      suppressive capacity of CD4+/CD25+ Tregs in chronically hemodialyzed patients.
      This response may contribute to the immune dysfunction, microinflammation, and
      atherogenesis observed in patients with ESRD.

PMID- 19406980
TI  - Loss of TIMP3 enhances interstitial nephritis and fibrosis.
AB  - The balance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix
      metalloproteinases (TIMPs) determines the integrity of the extracellular matrix.
      TIMP3 is the most highly expressed tissue inhibitor of metalloproteinase (TIMP)
      in the kidney, but its function in renal disease is incompletely understood. In
      this study, TIMP3-/- mice demonstrated an age-dependent chronic
      tubulointerstitial fibrosis. After unilateral ureteral obstruction (UUO), young
      TIMP3-/- mice exhibited increased renal injury (tubular atrophy, cortical and
      medullary thinning, and vascular damage) compared with wild-type mice. In
      addition, TIMP3-/- mice had greater interstitial fibrosis; increased synthesis
      and deposition of type I collagen; increased activation of fibroblasts; enhanced
      apoptosis; and greater activation of MMP2, but not MMP9, after UUO. TIMP3
      deficiency also led to accelerated processing of TNFalpha, demonstrated by
      significantly higher TACE activity and greater soluble TNFalpha levels by 3 d
      after UUO. The additional deletion of TNFalpha markedly reduced inflammation,
      apoptosis, and induction of a number of MMPs. Moreover, inhibition of MMPs in
      TIMP3-/-/TNFalpha-/- mice further abrogated postobstructive injury and prevented
      tubulointerestitial fibrosis. In humans, TIMP3 expression increased in the renal
      arteries and proximal tubules of subjects with diabetic nephropathy or chronic
      allograft nephropathy. Taken together, these results provide evidence that TIMP3
      is an important mediator of kidney injury, and regulating its activity may have
      therapeutic benefit for patients with kidney disease.

PMID- 19406982
TI  - Induction of epithelial-mesenchymal transition in primary airway epithelial cells
      from patients with asthma by transforming growth factor-beta1.
AB  - RATIONALE: Airway remodeling in asthma is associated with the accumulation of
      fibroblasts, the primary cell responsible for synthesis and secretion of
      extracellular matrix proteins. The process by which the number of fibroblasts
      increases in asthma is poorly understood, but epithelial-mesenchymal transition
      (EMT) may play a significant role. OBJECTIVES: To evaluate whether EMT occurs in
      primary airway epithelial cells (AECs), the mechanisms involved, and if this
      process is altered in asthmatic AECs. METHODS: AECs were obtained from subjects
      with asthma (n = 8) and normal subjects without asthma (n = 10). Monolayer and
      air-liquid interface-AEC (ALI-AEC) cultures were treated with transforming growth
      factor (TGF)-beta1 (10 ng/ml) for 72 hours and assayed for mesenchymal and
      epithelial markers using quantitative polymerase chain reaction, confocal
      microscopy, and immunoblot. The involvement of BMP-7, Smad3, and MAPK-mediated
      signaling were also evaluated. MEASUREMENTS AND MAIN RESULTS: TGF-beta1-induced
      EMT in AEC monolayers derived from subjects with asthma and normal donors. EMT
      was characterized by changes in cell morphology, increased expression of
      mesenchymal markers EDA-fibronectin, vimentin, alpha-smooth muscle actin, and
      collagen-1, and loss of epithelial markers E-cadherin and zonular occludin-1.
      Inhibition of TGF-beta1-induced signaling with Smad3-inhibiting siRNA or TGF
      beta1-neutralizing antibodies prevented and reversed EMT, respectively, whereas
      BMP-7 had no effect. In ALI-AEC cultures derived from normal subjects, EMT was
      confined to basally situated cells, whereas in asthmatic ALI-AEC cultures EMT was
      widespread throughout the epithelium. CONCLUSIONS: TGF-beta1 induces EMT in a
      Smad3-dependent manner in primary AECs. However, in asthmatic-derived ALI-AEC
      cultures, the number of cells undergoing EMT is greater. These findings support
      the hypothesis that epithelial repair in asthmatic airways is dysregulated.

PMID- 19406983
TI  - Continuous positive airway pressure treatment reduces mortality in patients with
      ischemic stroke and obstructive sleep apnea: a 5-year follow-up study.
AB  - RATIONALE: Obstructive sleep apnea (OSA) is an independent risk factor for
      stroke, but little is known about the role of continuous positive airway pressure
      (CPAP) on mortality in patients with stroke. OBJECTIVES: To analyze the
      independent impact of long-term CPAP treatment on mortality in patients with
      ischemic stroke. METHODS: Prospective observational study in 166 patients with
      ischemic stroke. Sleep study was performed in all of them and CPAP treatment was
      offered in the case of moderate to severe cases. Patients were followed-up for 5
      years to analyze the risk of mortality. MEASUREMENTS AND MAIN RESULTS: Of 223
      patients consecutively admitted for stroke, a sleep study was performed on 166 of
      them (2 mo after the acute event). Thirty-one had an apnea-hypopnea index (AHI)
      of less than 10; 39 had an AHI between 10 and 19, and 96 had an AHI of 20 or
      greater. CPAP treatment was offered when AHI was 20 or greater. Patients were
      followed up in our outpatient clinic at 1, 3, and 6 months, and for every 6
      months thereafter for 5 years (prospective observational study). Mortality data
      were recorded from our computer database and official death certificates. The
      mean age of subjects was 73.3 +/- 11 years (59% males), and the mean AHI was 26
      (for all patients with a predominance of obstructive events). Patients with an
      AHI of 20 or greater who did not tolerate CPAP (n = 68) showed an increase
      adjusted risk of mortality (hazards ratio [HR], 2.69; 95% confidence interval
      [CI], 1.32-5.61) compared with patients with an AHI of less than 20 (n = 70), and
      an increased adjusted risk of mortality (HR, 1.58; 95% CI, 1.01-2.49; P = 0.04)
      compared with patients with moderate to severe OSA who tolerated CPAP (n = 28).
      There were no differences in mortality among patients without OSA, patients with
      mild disease, and patients who tolerated CPAP. CONCLUSIONS: Our results suggest
      that long-term CPAP treatment in moderate to severe OSA and ischemic stroke is
      associated with a reduction in excess risk of mortality.

PMID- 19406985
TI  - Advanced electron microscopy in materials physics.

PMID- 19406984
TI  - Human neutrophil peptides and phagocytic deficiency in bronchiectatic lungs.
AB  - RATIONALE: A well-known clinical paradox is that severe bacterial infections
      persist in the lungs of patients with cystic fibrosis (CF) despite the abundance
      of polymorphonuclear neutrophils (PMN) and the presence of a high concentration
      of human neutrophil peptides (HNP), both of which are expected to kill the
      bacteria but fail to do so. The mechanisms remain unknown. OBJECTIVES: This study
      examined several possible mechanisms to understand this paradox. METHODS: PMN
      were isolated from sputum and blood of subjects with and without CF or non-CF
      bronchiectasis for phagocytic assays. HNP isolated from patients with CF were
      used to stimulate healthy PMN followed by phagocytic tests. MEASUREMENTS AND MAIN
      RESULTS: PMN isolated from the sputum of the bronchiectatic patients display
      defective phagocytosis that correlated with high concentrations of HNP in the
      lung. When healthy PMN were incubated with HNP, decreased phagocytic capacity was
      observed in association with depressed surface Fc gamma RIII, actin-filament
      remodeling, enhanced intracellular Ca(2+), and degranulation. Treatment of PMN
      with an intracellular Ca(2+) blocker or alpha1-proteinase inhibitor to attenuate
      the activity of HNP largely prevented the HNP-induced phagocytic deficiency.
      Intratracheal instillation of HNP in Pallid mice (genetically deficient in alpha1
      proteinase inhibitor) resulted in a greater PMN lung infiltration and phagocytic
      deficiency compared with wild-type mice. CONCLUSIONS: HNP or PMN alone exert
      antimicrobial ability, which was lost as a result of their interaction. These
      effects of HNP may help explain the clinical paradox seen in patients with
      inflammatory lung diseases, suggesting HNP as a novel target for clinical
      therapy.

PMID- 19406981
TI  - Substitution of moxifloxacin for isoniazid during intensive phase treatment of
      pulmonary tuberculosis.
AB  - RATIONALE: Moxifloxacin has potent activity against Mycobacterium tuberculosis in
      vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data
      regarding its activity in humans are limited. OBJECTIVES: Our objective was to
      compare the antimicrobial activity and safety of moxifloxacin versus isoniazid
      during the first 8 weeks of combination therapy for pulmonary TB. METHODS: Adults
      with sputum smear-positive pulmonary TB were randomly assigned to receive either
      moxifloxacin 400 mg plus isoniazid placebo, or isoniazid 300 mg plus moxifloxacin
      placebo, administered 5 days/week for 8 weeks, in addition to rifampin,
      pyrazinamide, and ethambutol. All doses were directly observed. Sputum was
      collected for culture every 2 weeks. The primary outcome was negative sputum
      culture at completion of 8 weeks of treatment. MEASUREMENTS AND MAIN RESULTS: Of
      433 participants enrolled, 328 were eligible for the primary efficacy analysis.
      Of these, 35 (11%) were HIV positive, 248 (76%) had cavitation on baseline chest
      radiograph, and 213 (65%) were enrolled at African sites. Negative cultures at
      Week 8 were observed in 90/164 (54.9%) participants in the isoniazid arm, and
      99/164 (60.4%) in the moxifloxacin arm (P = 0.37). In multivariate analysis,
      cavitation and enrollment at an African site were associated with lower
      likelihood of Week-8 culture negativity. The proportion of participants who
      discontinued assigned treatment was 31/214 (14.5%) for the moxifloxacin group
      versus 22/205 (10.7%) for the isoniazid group (RR, 1.35; 95% CI, 0.81, 2.25).
      CONCLUSIONS: Substitution of moxifloxacin for isoniazid resulted in a small but
      statistically nonsignificant increase in Week-8 culture negativity.

PMID- 19406986
TI  - NK-cell-mediated killing of target cells triggers robust antigen-specific T-cell
      mediated and humoral responses.
AB  - Previous work showed that administration of antigen-expressing apoptotic cells in
      vivo results in antigen-specific CD8+ T-cell responses independent of Toll-like
      receptor signaling. We report here that natural killer (NK) cells can serve a
      function directly upstream of this pathway and initiate robust adaptive immune
      responses via killing of antigen-expressing target cells. This pathway is highly
      sensitive, in that administration of as few as 10(4) target cells induced
      detectable antigen-specific CD8+ T-cell responses. Importantly, NK cell-mediated
      cytotoxicity of target cells could also induce robust antigen-specific CD4+ T
      cell responses, which were critical for subsequent CD8+ T-cell priming and IgG
      responses. Unlike adaptive immune responses induced by gamma-irradiated cells,
      the NK-cell pathway required myeloid differentiating factor 88 (MyD88) and
      Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-beta
      (Trif) signaling. NK cells have previously been shown to detect and kill pathogen
      infected host cells, as well as neoplastic cells and tissue allografts. The
      present data provide further evidence that they also discharge a strong tie with
      their relatives in the adaptive immune system. We think that the recognition and
      killing of target cells by NK cells represents an important pathway for the
      generation of robust CD8+ T and humoral responses that may be exploited for
      vaccine development.

PMID- 19406987
TI  - KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative
      dysfunction of highly differentiated CD8+ T cells.
AB  - Highly differentiated CD8+CD28-CD27- T cells have short telomeres, defective
      telomerase activity, and reduced capacity for proliferation, indicating that they
      are close to replicative senescence. In addition, these cells express increased
      levels of the senescence-associated inhibitory receptor KLRG1 and have poor
      capacity for IL-2 synthesis and defective Akt (ser(473)) phosphorylation after
      activation. It is not known whether signaling via KLRG1 contributes to any of the
      attenuated differentiation-related functional changes in CD8+ T cells. To address
      this, we blocked KLRG1 signaling during T-cell receptor activation using
      antibodies against its major ligand, E-cadherin. This resulted in a significant
      enhancement of Akt (ser(473)) phosphorylation and T-cell receptor-induced
      proliferative activity of CD8+CD28-CD27- T cells. Furthermore, the increase of
      proliferation was directly linked to the Akt-mediated induction of cyclin D and E
      and reduction in the cyclin inhibitor p27 expression. In contrast, the reduced
      telomerase activity in highly differentiated CD8+CD28(-)CD27- T cells was not
      altered by KLRG1 blockade, indicating the involvement of other mechanisms. This
      is the first demonstration of a functional role for KLRG1 in primary human CD8+ T
      cells and highlights that certain functional defects that arise during
      progressive T-cell differentiation toward replicative senescence are maintained
      actively by inhibitory receptor signaling.

PMID- 19406988
TI  - High-resolution genomic profiling of childhood T-ALL reveals frequent copy-number
      alterations affecting the TGF-beta and PI3K-AKT pathways and deletions at 6q15
      16.1 as a genomic marker for unfavorable early treatment response.
AB  - Precursor T-cell acute lymphoblastic leukemia (T-ALL) in children represents a
      clinical challenge, because relapses are usually fatal. It is thus necessary to
      identify high-risk patients as early as possible to effectively individualize
      treatment. We aimed to define novel molecular risk markers in T-ALL and performed
      array-based comparative genomic hybridization (array-CGH) and expression analyses
      in 73 patients. We show that DNA copy-number changes are common in T-ALL and
      affect 70 of 73 (96%) patients. Notably, genomic imbalances predicted to down
      regulate the TGF-beta or up-regulate the PI3K-AKT pathways are identified in 25
      of 73 (34%) and 21 of 73 (29%) patients, suggesting that these pathways play key
      roles in T-ALL leukemogenesis. Furthermore, we identified a deletion at 6q15-16.1
      in 9 of 73 (12%) of the patients, which predicts poor early treatment response.
      This deletion includes the CASP8AP2 gene, whose expression is shown to be down
      regulated. The interaction of CASP8AP2 with CASP8 plays a crucial role in
      apoptotic regulation, suggesting a functional link between the clinical effect of
      the deletion and the molecular mode of action. The data presented here implicate
      the TGF-beta and PI3K-AKT pathways in T-ALL leukemogenesis and identify a
      subgroup of patients with CASP8AP2 deletions and poor early treatment response.

PMID- 19406989
TI  - TGF-beta induces degradation of TAL1/SCL by the ubiquitin-proteasome pathway
      through AKT-mediated phosphorylation.
AB  - T-cell acute lymphoblastic leukemia 1 (TAL1), also known as stem cell leukemia
      (SCL), plays important roles in differentiation of hematopoietic and endothelial
      cells and is deregulated in a high percentage of T-cell acute lymphoblastic
      leukemia (T-ALL). In this report we show that the intracellular concentration of
      TAL1 is regulated by transforming growth factor beta (TGF-beta), which triggers
      its polyubiquitylation and degradation by the proteasome. This effect is mediated
      by AKT1, which phosphorylates TAL1 at threonine 90. Immunoprecipitation
      experiments showed that this event increases association of TAL1 with the E3
      ubiquitin ligase CHIP. The E47 heterodimerization partner of TAL1 hinders this
      association. Our observations indicate that activation of the TGF-beta and
      phosphatidylinositol 3-kinase/AKT pathways might reverse overexpression of TAL1
      in leukemic cells by inducing proteolysis of this important oncogene.

PMID- 19406990
TI  - Very small embryonic/epiblast-like stem cells: a missing link to support the germ
      line hypothesis of cancer development?
AB  - The morphology of several tumors mimics developmentally early tissues, and tumors
      often express early developmental markers characteristic of the germ line
      lineage. The presence of these markers in neoplastic cells could reflect the
      dedifferentiation of somatic cells in which cancer develops or cancer origination
      in primitive stem cells closely related to the epiblast/germ line. The
      identification of primitive germ line-derived very small embryonic/epiblast-like
      stem cells, which are deposited early in embryogenesis in developing organs and
      persist in several organs into adulthood, raised the possibility that cancer may
      originate in these cells. In this review, we hypothesize that very small
      embryonic/epiblast-like stem cells could be a missing link that support the more
      than 100-year-old concepts of the embryonic rest or germ line origin hypotheses
      of cancer development; however, further experimental evidence is needed to
      support this hypothesis.

PMID- 19406991
TI  - Homeostatic role of transforming growth factor-beta in the oral cavity and
      esophagus of mice and its expression by mast cells in these tissues.
AB  - Transforming growth factor-beta (TGF-beta) is a pleiotropic growth factor; its
      overexpression has been implicated in many diseases, making it a desirable target
      for therapeutic neutralization. In initial safety studies, mice were chronically
      treated (three times per week) with high doses (50 mg/kg) of a murine, pan
      neutralizing, anti-TGF-beta antibody. Nine weeks after the initiation of
      treatment, a subset of mice exhibited weight loss that was concurrent with
      decreased food intake. Histopathology revealed a unique, nonneoplastic cystic
      epithelial hyperplasia and tongue inflammation, as well as dental dysplasia and
      epithelial hyperplasia and inflammation of both the gingiva and esophagus. In an
      effort to determine the cause of this site-specific pathology, we examined TGF
      beta expression in these tissues and saliva under normal conditions. By
      immunostaining, we found higher expression levels of active TGF-beta1 and TGF
      beta3 in normal tongue and esophageal submucosa compared with gut mucosal
      tissues, as well as detectable TGF-beta1 in normal saliva by Western blot
      analysis. Interestingly, mast cells within the tongue, esophagus, and skin co
      localized predominantly with the TGF-beta1 expressed in these tissues. Our
      findings demonstrate a novel and restricted pathology in oral and esophageal
      tissues of mice chronically treated with anti-TGF-beta that is associated with
      basal TGF-beta expression in saliva and by mast cells within these tissues. These
      studies illustrate a previously unappreciated biological role of TGF-beta in
      maintaining homeostasis within both oral and esophageal tissues.

PMID- 19406992
TI  - Mucosal tolerance induced by an immunodominant peptide from rat alpha3(IV)NC1 in
      established experimental autoimmune glomerulonephritis.
AB  - Experimental autoimmune glomerulonephritis (EAG), an animal model of
      Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by immunization
      with the noncollagenous domain of the alpha 3 chain of type IV collagen,
      alpha3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24
      38), from the N-terminus of rat alpha3(IV)NC1; this peptide contains the major B-
      and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we
      investigated the mechanisms of mucosal tolerance in EAG by examining the effects
      of the nasal administration of this peptide after the onset of disease. A dose
      dependent effect was observed: a dose of 300 microg had no effect, a dose of 1000
      microg resulted in a moderate reduction in EAG severity, and a dose of 3000
      microg produced a marked reduction in EAG severity accompanied by diminished
      antigen-specific, T-cell proliferative responses. These results demonstrate that
      mucosal tolerance in EAG can be induced by nasal administration of an
      immunodominant peptide from the N-terminus of alpha3(IV)NC1 and should be of
      value in designing new therapeutic strategies for patients with Goodpasture's
      disease and other autoimmune disorders.

PMID- 19406994
TI  - Closer to the truth in AML.

PMID- 19406995
TI  - The changing definition of CLL.

PMID- 19406993
TI  - Erbb2 suppresses DNA damage-induced checkpoint activation and UV-induced mouse
      skin tumorigenesis.
AB  - The Erbb2 receptor is activated by UV irradiation, the primary cause of non
      melanoma skin cancer. We hypothesized that Erbb2 activation contributes to UV
      induced skin tumorigenesis by suppressing cell cycle arrest. Consistent with this
      hypothesis, inhibition of Erbb2 in v-ras(Ha) transgenic mice before UV exposure
      resulted in both 56% fewer skin tumors and tumors that were 70% smaller.
      Inhibition of the UV-induced activation of Erbb2 also resulted in milder
      epidermal hyperplasia, S-phase accumulation, and decreased levels of the cell
      cycle regulator Cdc25a, suggesting altered cell cycle regulation on inhibition of
      Erbb2. Further investigation using inhibition or genetic deletion of Erbb2 in
      vitro revealed reduced Cdc25a levels and increased S-phase arrest in UV
      irradiated cells lacking Erbb2 activity. Ectopic expression of Cdc25a prevented
      UV-induced S-phase arrest in keratinocytes lacking Erbb2 activity, demonstrating
      that maintenance of Cdc25a by Erbb2 suppresses cell cycle arrest. Examination of
      checkpoint pathway activation upstream of Cdc25a revealed Erbb2 activation did
      not alter Ataxia Telangiectasia and Rad3-related/Ataxia Telangiectasia Mutated
      activity but increased inhibitory phosphorylation of Chk1-Ser(280). Since Akt
      phosphorylates Chk1-Ser(280), the effect of Erbb2 on phosphatidyl inositol-3
      kinase (PI3K)/Akt signaling during UV-induced cell cycle arrest was determined.
      Erbb2 ablation reduced the UV-induced activation of PI3K while inhibition of
      PI3K/Akt increased UV-induced S-phase arrest. Thus, UV-induced Erbb2 activation
      increases skin tumorigenesis through inhibitory phosphorylation of Chk1, Cdc25a
      maintenance, and suppression of S-phase arrest via a PI3K/Akt-dependent
      mechanism.

PMID- 19406996
TI  - Mesenchymally "stemming" angiogenesis.

PMID- 19406997
TI  - Hiding from ABT-737 in lymph nodes.

PMID- 19406998
TI  - MicroRNAs to know in Waldenstrom macroglobulinemia.

PMID- 19406999
TI  - How can fibrinolysis induce cell death?

PMID- 19407000
TI  - Lymphangiogenesis factors: a target for therapy?

PMID- 19407003
TI  - Communicating stereotype-relevant information: is factual information subject to
      the same communication biases as fictional information?
AB  - Factual information is more frequently read and discussed than fictional
      information. However, research on the role of communication in shaping
      stereotypes has focused almost exclusively on fictional narratives. In
      Experiments 1 and 2 a newspaper article containing information about heroin users
      was communicated along chains of 4 people. No stereotype-consistency bias was
      observed. Instead, a greater proportion of stereotype-inconsistent information
      was communicated than was stereotype-consistent or -neutral information. Three
      further experiments investigated explanations for the difference between the
      communication of fictional and factual information. Experiment 3 ruled out the
      possibility that participants' beliefs about the validity of the information
      could influence the way that it is communicated. Experiments 4 and 5 divided
      information into concrete (a specific event or fact) or abstract (opinion). A
      stereotype-consistency bias emerged only for abstract information. In summary,
      linguistic abstraction moderates whether stereotype-consistency biases emerge in
      the communication of stereotype-relevant factual information.

PMID- 19407001
TI  - Malignant stem cells in childhood ALL: the debate continues!

PMID- 19407004
TI  - The effect of stereotype threat on the solving of quantitative GRE problems: a
      mere effort interpretation.
AB  - The mere effort account argues that stereotype threat motivates participants to
      want to perform well, which potentiates prepotent responses. If the prepotent
      response is correct, performance is facilitated. If incorrect and participants do
      not know, or lack the knowledge or time required for correction, performance is
      debilitated. The Graduate Record Examinations (GRE) quantitative test is made up
      of two problem types: (a) solve problems, which require the solution of an
      equation, and (b) comparison problems, which require the use of logic and
      estimation. Previous research shows that the prepotent tendency is to attempt to
      solve the equations. Consistent with mere effort predictions, Experiment 1
      demonstrates that threatened participants perform better than controls on solve
      problems (prepotent response correct) but worse than controls on comparison
      problems (prepotent response incorrect). Experiment 2 shows that a simple
      instruction as to the correct solution approach eliminates the performance
      deficit on comparison problems.

PMID- 19407005
TI  - An evolutionary perspective on humor: sexual selection or interest indication?
AB  - Are people who are funny more attractive? Or does being attractive lead people to
      be seen as funnier? The answer may depend on the underlying evolutionary function
      of humor. While humor has been proposed to signal "good genes," the authors
      propose that humor also functions to indicate interest in social relationships-in
      initiating new relationships and in monitoring existing ones. Consistent with
      this interest indicator model, across three studies both sexes were more likely
      to initiate humor and to respond more positively and consider the other person to
      be funny when initially attracted to that person. The findings support that humor
      dynamics--and not just humor displays--influence romantic chemistry for both men
      and women, suggesting that humor can ultimately function as a strategy to
      initiate and monitor social relationships.

PMID- 19407007
TI  - Supernormal ERG oscillatory potentials in transgenic rabbit with rhodopsin P347L
      mutation and retinal degeneration.
AB  - PURPOSE: To determine the properties of the retina of a rhodopsin P347L
      transgenic (Tg) rabbit model of retinal degeneration by electroretinography
      (ERG). METHODS: Full-field ERGs were recorded in 12- to 48-week-old wild-type
      (WT) and Tg rabbits. The a-wave was analyzed by the a-wave fitting model of Hood
      and Birch. The stimulus-response function of the b-wave was analyzed by the
      Michaelis-Menten equation. Oscillatory potentials (OPs) were extracted by digital
      filtering after subtracting the a-wave. OPs were also recorded before and after
      an intravitreal injection of l-2 amino-4-phosphonobutyric acid (APB), cis-2,3
      piperidine dicarboxylic acid (PDA), gamma-amino butyric acid (GABA), or
      tetrodotoxin citrate (TTX). RESULTS: All the ERG components of Tg rabbits
      decreased progressively with age with the a-wave more affected than the b-wave,
      and the OPs were most preserved. Of interest, the summed OP amplitudes of the Tg
      rabbits were significantly larger than those of WT rabbits when they were 12
      weeks of age. The changes in the amplitudes of the OPs after intravitreal
      injections of APB, PDA, or GABA in Tg rabbits did not differ significantly from
      those of WT rabbits. However, injection of TTX resulted in a significantly larger
      amplitude reduction of the OPs in Tg (65.3%) than in WT (28.6%) rabbits.
      CONCLUSIONS: The significantly larger OPs in Tg rabbits resulted from alterations
      in the inner retinal neurons. The greater effect of TTX on the OP amplitudes in
      Tg rabbits suggests that the supernormal OPs in Tg rabbits may be related to
      secondary changes in the spiking neurons of the inner retina after photoreceptor
      degeneration.

PMID- 19407006
TI  - Anti-angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid
      mediators.
AB  - PURPOSE: Resolvins and lipoxins are lipid mediators generated from essential
      polyunsaturated fatty acids that are the first dual anti-inflammatory and pro
      resolving signals identified in the resolution phase of inflammation. Here the
      authors investigated the potential of aspirin-triggered lipoxin (LX) A4 analog
      (ATLa), resolving (Rv) D1, and RvE1, in regulating angiogenesis in a murine
      model. METHODS: ATLa and RvE1 receptor expression was tested in different corneal
      cell populations by RT-PCR. Corneal neovascularization (CNV) was induced by
      suture or micropellet (IL-1 beta, VEGF-A) placement. Mice were then treated with
      ATLa, RvD1, RvE1, or vehicle, subconjunctivally at 48-hour intervals.
      Infiltration of neutrophils and macrophages was quantified after
      immunofluorescence staining. The mRNA expression levels of inflammatory
      cytokines, VEGFs, and VEGFRs were analyzed by real-time PCR. CNV was evaluated
      intravitally and morphometrically. RESULTS: The receptors for LXA4, ALX/Fpr-rs-2
      and for RvE1, ChemR23 were each expressed by epithelium, stromal keratocytes, and
      infiltrated CD11b(+) cells in corneas. Compared to the vehicle-treated eye, ATLa
      , RvD1-, and RvE1-treated eyes had reduced numbers of infiltrating neutrophils
      and macrophages and reduced mRNA expression levels of TNF-alpha, IL-1 alpha, IL-1
      beta, VEGF-A, VEGF-C, and VEGFR2. Animals treated with these mediators had
      significantly suppressed suture-induced or IL-1 beta-induced hemangiogenesis (HA)
      but not lymphangiogenesis. Interestingly, only the application of ATLa
      significantly suppressed VEGF-A-induced HA. CONCLUSIONS: ATLa, RvE1, and RvD1 all
      reduce inflammatory corneal HA by early regulation of resolution mechanisms in
      innate immune responses. In addition, ATLa directly inhibits VEGF-A-mediated
      angiogenesis and is the most potent inhibitor of NV among this new genus of dual
      anti-inflammatory and pro-resolving lipid mediators.

PMID- 19407008
TI  - Evaluation of 9-cis-retinyl acetate therapy in Rpe65-/- mice.
AB  - PURPOSE: Mice lacking retinal pigment epithelium-specific 65-kDa protein (RPE65)
      develop retinopathy and blindness resembling Leber congenital amaurosis. Effects
      of 9-cis-retinyl acetate (9-cis-R-Ac) on visual function and retinopathy
      progression were tested in Rpe65(-/-) mice. METHODS: Young C57Bl/6 mice were
      given 9-cis-R-Ac in each of four different oil-based vehicle solutions by gastric
      gavage to identify the vehicle most suitable for drug delivery by measuring
      retinoid levels in plasma. Then doses of 9-cis-R-Ac ranging from 1 to 100 mg/kg
      were administered to 5- to 12-week-old Rpe65(-/-) mice by different treatment
      regimens, including single doses and either intermittent or daily doses for
      various periods up to 8 weeks. Retinoid effects on visual function were evaluated
      by electroretinography, retinoid analyses, histologic methods, and vision
      dependent behavioral testing. RESULTS: Soybean oil vehicle provided the highest 9
      cis-R-Ac metabolite levels in plasma. Single doses of 9-cis-R-Ac (6.25-50 mg/kg)
      provided significant dose-dependent improvement in electroretinographic
      responses. Well-tolerated daily doses (1-12.5 mg/kg) for 2 weeks induced
      remarkable improvement of retinal function. Significant dose-dependent
      improvement of electroretinographic responses was observed 6 days after
      administration of 9-cis-R-Ac daily for 3 days at 1 to 12.5 mg/kg. Mice given
      either daily or intermittent 9-cis-R-Ac treatment at 1 and 4 mg/kg and evaluated
      8 weeks later displayed dose-dependent improvement of retinal function and
      morphology, whereas retinal function deteriorated in control animals. Treated
      mice also performed better than control animals in vision-dependent behavioral
      tests. CONCLUSIONS: Treatment with 9-cis-R-Ac improves visual function and
      preserves retinal morphology in Rpe65(-/-) mice.

PMID- 19407009
TI  - A new Fgf10 mutation in the mouse leads to atrophy of the harderian gland and
      slit-eye phenotype in heterozygotes: a novel model for dry-eye disease?
AB  - PURPOSE: The purpose of the present study was to characterize a new slit-eye
      phenotype in the mouse. METHODS: Genomewide linkage analysis was performed, and a
      candidate gene was sequenced. Eyes of the mutants were described morphologically,
      histologically, and by in situ hybridization. To allow morphologic and functional
      studies of the retina, mutants were outcrossed to C57BL/6. RESULTS: Within an
      ongoing ethyl-nitrosourea mutagenesis screen with C3HeB/FeJ mice, the authors
      identified a new mutant (referred to as Aey17) showing a slit-eye phenotype in
      heterozygotes; homozygous mutants are not viable because of major developmental
      defects. This mutation was mapped to the distal end of mouse chromosome 13,
      suggesting Fgf10 (encoding the fibroblast growth factor 10) as a candidate gene.
      An A-->G transition in the penultimate base of the first intron of Fgf10 leading
      to aberrant splicing with an additional 49 bp in exon 2 and to a frameshift with
      a premature stop codon after 54 new amino acids was identified. Histologic
      analysis of the major ocular tissues (cornea, lens, retina) did not reveal major
      alterations compared with the wild type, but the size of the Harderian gland was
      remarkably reduced in heterozygotes. Although Fgf10 was expressed in the
      developing retina, neither electroretinography nor the virtual drum indicated any
      abnormalities in heterozygous mutants; overall eye size was identical in wild
      types and heterozygotes. CONCLUSIONS: The mutation in the Fgf10 gene leads to a
      dominant slit-eye phenotype caused by atrophy of the Harderian gland.

PMID- 19407010
TI  - Effect of intravitreal injection of high-dose bevacizumab in monkey eyes.
AB  - PURPOSE: To evaluate the ocular complications of intravitreal injection of high
      dose bevacizumab in monkey eyes. METHODS: Four healthy monkeys (Macaca fuscata)
      received an intravitreal injection of either 6.25 or 12.5 mg bevacizumab in the
      right eye; the left control eye received an intravitreal injection of the same
      volume of saline. The eyes were examined using slit lamp and funduscopy, optical
      coherence tomography (OCT), electroretinography (ERG), fundus photography (FP),
      fluorescein angiography (FA), and indocyanine green angiography (ICGA). The eyes
      were enucleated 28 days after the intravitreal injection and subjected to light
      microscopy. RESULTS: No pathologic changes were observed by FP, FA, ICGA, OCT,
      and light microscopy in the eyes injected with either of the two bevacizumab
      doses. ERG showed no toxic change in the eyes that received the 6.25-mg dose. In
      two eyes that received the 12.5-mg dose, ERG showed no significant difference
      between the right and left eyes 4 weeks after injection, although there were
      transient changes in scotopic responses. CONCLUSIONS: No irreversible toxic
      effects were observed in monkey eyes receiving an intravitreal injection of high
      dose bevacizumab.

PMID- 19407011
TI  - Cone outer segment morphology and cone function in the Rpe65-/- Nrl-/- mouse
      retina are amenable to retinoid replacement.
AB  - PURPOSE: RPE65, a major retinal pigment epithelium protein, is essential in
      generating 11-cis retinal, the chromophore for all opsins. Without chromophore,
      cone opsins are mislocalized and cones degenerate rapidly (e.g., Rpe65(-/-)
      mouse). Function, survival, and correct targeting of opsins is increased in
      Rpe65(-/-) cones on supplying 11-cis retinal. Here, we determine the consequences
      of 11-cis retinal withdrawal and supplementation on cone development in the all
      cone Nrl(-/-) retina. METHODS: Rpe65(-/-) Nrl(-/-), Nrl(-/-), and wild-type mice
      were examined. Cone structure was analyzed by using TUNEL assay, electron
      microscopy, and cone-specific antibodies. Cone function was assessed with light
      adapted single-flash ERGs. RESULTS: Rpe65(-/-)Nrl(-/-) mice had an increased
      number of TUNEL-positive photoreceptors during programmed cell death compared
      with Nrl(-/-) mice, in addition to accelerated age-related degeneration. Cone
      function in Rpe65(-/-)Nrl(-/-) mice was minimal, and opsins were mislocalized.
      Treatment with 11-cis retinal restored cone function, promoted outer segment
      formation, and enabled opsin trafficking to outer segments. Eliminating Rpe65
      prevented rosette formation in Nrl(-/-) retinas; supplementation of Rpe65(-/
      )Nrl(-/-) mice with 11-cis retinal resulted in their reoccurrence. CONCLUSIONS:
      Taken together, function and opsin trafficking in Nrl(-/-) and wild-type cones
      are comparable, confirming and extending our findings that cone maturation and
      outer segment development are dependent on the presence of chromophore. The data
      on age-related cone death in Rpe65(-/-)Nrl(-/-) mice and the reintroduction of
      rosettes after 11-cis retinal injections confirm that outer segments, which for
      steric reasons appear to introduce rosettes in an all-cone retina, are essential
      for cell survival. These results are important for understanding and treating
      chromophore-related cone dystrophies.

PMID- 19407013
TI  - Increased vitronectin production by complement-stimulated human retinal pigment
      epithelial cells.
AB  - PURPOSE: A variation in the complement factor H gene was associated with an
      enhanced risk to develop especially early age-related macular degeneration.
      Drusen and basal laminar deposits are hallmarks of this AMD manifestation that
      contain vitronectin as a major component. In this study, the correlation between
      complement stimulation and vitronectin production of retinal pigment epithelial
      (RPE) cells was investigated. METHODS: ARPE-19 cells, a permanent cell line of
      human RPE cells, were supplemented with and without human complement competent
      serum in medium with and without heat inactivated fetal calf serum. The cells
      were examined in situ for their vitronectin production as an effective inhibitor
      of alternatively activated complement by immunohistochemistry. Semi-quantitative
      RT-PCR and Western blots were performed to analyze vitronectin mRNA and protein.
      RESULTS: A strong immunohistochemical staining for vitronectin was observed after
      complement supplementation. The enhanced production of this complement
      inactivator by ARPE-19 cells was confirmed by Western blot, whereas the
      expression analysis revealed unaltered mRNA amounts. CONCLUSIONS: A stimulation
      of RPE cells with complement resulted in an upregulated production of
      vitronectin. This may support the concept of a protective mechanism, since
      vitronectin is the major inhibitor of complement activated by the alternative
      pathway. On the other hand, this increased vitronectin production after
      complement stimulation may contribute to focal or diffuse deposits in Bruch's
      membrane, as observed in early AMD.

PMID- 19407012
TI  - Mucin-type O-glycans in tears of normal subjects and patients with non-Sjogren's
      dry eye.
AB  - PURPOSE: O-linked carbohydrates (O-glycans) contribute to the hydrophilic
      character of mucins in mucosal tissues. This study was conducted to identify the
      repertoire of O-glycans in the tear film and the glycosyltransferases associated
      with their biosynthesis, in normal subjects and patients with non-Sjogren's dry
      eye. METHODS: Human tear fluid was collected from the inferior conjunctival
      fornix. O-glycans were released by hydrazinolysis, labeled with 2-aminobenzamide,
      and analyzed by fluorometric, high-performance liquid chromatography (HPLC)
      coupled with exoglycosidase digestions. O-glycan structures identified in tears
      were related to potential biosynthetic pathways in human conjunctival epithelium
      by using a glycogene microarray database. Lectin-binding analyses were performed
      with agglutinins from Arachis hypogaea, Maackia amurensis, and Sambucus nigra.
      RESULTS: The O-glycan profile of human tears consisted primarily of core 1 (Gal
      beta 1-3GalNAc alpha 1-Ser/Thr)-based structures. Mono-sialyl O-glycans
      represented approximately 66% of the glycan pool, with alpha2-6-sialyl core 1
      being the predominant O-glycan structure in human tears (48%). Four families of
      glycosyltransferases potentially related to the biosynthesis of these structures
      were identified in human conjunctiva. These included 13 polypeptide-GalNAc
      transferases (GALNT), the core 1 beta-3-galactosyltransferase (T-synthase), three
      alpha2-6-sialyltransferases (ST6GalNAc), and two alpha2-3-sialyltransferases
      (ST3Gal). No significant differences in total amount of O-glycans were detected
      between tears of normal subjects and patients with dry eye, by HPLC and lectin
      blot. Likewise, no differences in glycosyltransferase expression were found by
      glycogene microarray. CONCLUSIONS: This study identified the most common mucin
      type O-glycans in human tears and their expected biosynthetic pathways in ocular
      surface epithelia. Patients with non-Sjogren's dry eye showed no alterations in
      composition and amount of O-glycans in the tear fluid.

PMID- 19407014
TI  - Release of soluble tumor necrosis factor receptor 1 from corneal epithelium by
      TNF-alpha-converting enzyme-dependent ectodomain shedding.
AB  - PURPOSE: An involvement of tumor necrosis factor-alpha-converting enzyme (TACE)
      dependent ectodomain shedding in the release of soluble tumor necrosis factor
      receptor 1 (sTNFR1) from corneal epithelium was evaluated. METHODS: In vitro
      experiments were performed using the human SV40-transformed human corneal
      epithelial cell (HCEC) line. Ectodomain shedding was stimulated by phorbol
      myristate acetate (PMA, 3 microM) or peptidoglycan (PGN, 100 microg/mL), with or
      without TACE inhibition, using TNF-alpha processing inhibitor-1 (TAPI-1, 250
      microg/mL) or tissue inhibitor of metalloproteinase-3 (TIMP-3, 2 microg/mL) by
      addition to the HCEC culture medium. The concentrations of sTNFR1 in culture
      medium were analyzed by enzyme-linked immunosorbent assay. To induce an
      inflammatory response in the ocular surface, corneal alkali burn of BALB/c mice
      was made from a filter paper dipped in 1 N NaOH solution. TNFR1 expression in
      corneal and conjunctival epithelia was evaluated by immunohistochemistry 28 days
      after wounding. RESULTS: In HCEC culture medium, sTNFR1 release was significantly
      increased by the addition of PMA (t-test, P < 0.01) or PGN (P < 0.01). The
      increased release of sTNFR1 was significantly inhibited by the addition of TAPI-1
      or TIMP-3, indicating the possibility of TACE-dependent ectodomain shedding of
      TNFR1. In the corneal alkali burn model, TNFR1 was expressed in corneal and
      conjunctival epithelia. CONCLUSIONS: TACE-dependent ectodomain shedding of sTNFR1
      was recognized in corneal epithelium. In the inflamed ocular surface, TNFR1 was
      expressed in the corneal and conjunctival epithelia after alkali burn treatment.
      sTNFR1, released from the ocular surface, may play an anti-inflammatory role in
      the inflammatory condition.

PMID- 19407015
TI  - In vitro evidence of nerve growth factor effects on human conjunctival epithelial
      cell differentiation and mucin gene expression.
AB  - PURPOSE: Mucins released into the tear film are crucial to maintaining a healthy
      ocular surface. Alterations in goblet cell numbers and mucin secretion are
      observed in chronic ocular surface inflammatory diseases. Nerve growth factor
      (NGF) plays a crucial role in healing and inflammation of the ocular surface. The
      aim of this study was to evaluate in vitro the effect of NGF on conjunctival
      goblet cell differentiation and mucin production and secretion. METHODS: Human
      conjunctival epithelial cells were exposed to increasing NGF concentrations (1 to
      250 ng/mL) and analyzed to quantify cell growth (MTT/Ki67/BrdU), goblet cell
      differentiation (PAS/MUC5AC confocal staining), and mucin mRNA expression (real
      time PCR). Secreted and cellular MUC5AC were also analyzed by sandwich-ELISA and
      FACS, respectively. To confirm the biological effects of NGF, the same
      evaluations were performed on primary cultures, and changes in markers of
      stemness (p63) and commitment (14-3-3 sigma) were also investigated. RESULTS: In
      cell cultures, NGF induced a dose-dependent increase of goblet cell numbers,
      MUC5AC production, storage, and release. Additionally, in primary cultures, NGF
      induced an increase of abortive colonies and 14-3-3 sigma protein, and a decrease
      of p63 mRNA and protein, suggesting a differentiating effect of NGF on human
      conjunctival epithelium. CONCLUSIONS: These findings show that NGF might play a
      role in the complex mechanism leading to conjunctival epithelium differentiation
      and mucin secretion. In addition to the known roles of NGF in promoting ocular
      surface healing and sensitivity, its effects on conjunctival goblet cells support
      a rationale to investigate the therapeutic effectiveness of NGF in dry eye
      disease.

PMID- 19407016
TI  - Photoreceptor neuroprotection in RCS rats via low-dose intravitreal sustained
      delivery of fluocinolone acetonide.
AB  - PURPOSE: To study the neuroprotective effects of intravitreal fluocinolone
      acetonide (FA) in Royal College of Surgeons (RCS) rats. METHODS: Five-week-old
      RCS rats were divided into four groups: 0.5 microg/d FA-loaded intravitreal drug
      delivery implant (IDDI); 0.2 microg/d FA-loaded IDDI; inactive IDDI; and
      nonsurgical control. Electroretinography (ERG) and intraocular pressure (IOP)
      measurements were performed before surgery and weekly thereafter. Thicknesses of
      the retinal outer (ONL) and inner (INL) nuclear layers were evaluated at 9 weeks
      of age. ED-1-labeled activated microglia were counted. Total microglial cell
      counts were made by using Iba-1 antibody labeling. RESULTS: At 9 weeks, control
      groups demonstrated an 80% reduction in ERG amplitudes (P < 0.001 for both
      groups). FA-treated groups demonstrated no statistically significant attenuation
      of ERG amplitudes at the end of the study, compared with the initial ERGs.
      Intraocular pressure (IOP) remained normal in all groups. ONL thickness in FA 0.2
      microg/d-treated eyes was 2.1 +/- 0.5 times greater than in nonsurgical eyes (P <
      0.001) and 3.4 +/- 0.7 times greater than in inactive IDDI-treated eyes (P <
      0.0001). In FA 0.5 microg/d-treated eyes, ONL thickness was 1.5 +/- 0.1 times
      higher than in nonsurgical controls (P < 0.05) and 2.4 +/- 0.4 times higher than
      in inactive IDDI-treated eyes (P < 0.01). INL thickness was not different among
      groups. FA-treated eyes demonstrated significantly fewer activated microglia (P <
      0.001) and overall number of microglia in the photoreceptor and outer debris zone
      layers (P < 0.001), compared with control groups. CONCLUSIONS: Chronic
      intravitreal infusion of FA is neuroprotective in RCS rats, preserves ONL
      morphology and ERG amplitudes and reduces retinal neuroinflammation. These
      findings may have a therapeutic role in human photoreceptor cell degenerations.

PMID- 19407018
TI  - Intracellular flow in optic nerve axons: a mechanism for cell death in glaucoma.
AB  - PURPOSE: In glaucoma, elevated intraocular pressure causes a progressive loss of
      retinal ganglion cells and results in optic neuropathy. The authors propose a
      potential mechanism for cell death, whereby elevated intraocular pressure causes
      fluid to permeate axonal membranes, creating a passive intracellular fluid flow
      within the axons. It is hypothesized that this intracellular flow locally
      depletes the adenosine triphosphate (ATP) concentration, disrupting axonal
      transport and leading to cell death. METHODS: A mathematical model was developed
      that takes into account the biomechanical principles underpinning the proposed
      hypothesis, and was solved to determine the implications of the mechanism.
      RESULTS: The model suggests that the raised intraocular pressures present in
      glaucoma are adequate to produce significant intracellular fluid flow. In the
      periphery of the optic nerve head, this flow may be sufficient to disrupt the
      diffusion of ATP and hence interrupt active axonal transport. CONCLUSIONS: The
      mathematical model demonstrates that it is physically plausible that a passive
      intracellular fluid flow could significantly contribute to the pathophysiology of
      the retinal ganglion cell axon in glaucoma.

PMID- 19407017
TI  - Cholinergic responses of ophthalmic arteries in M3 and M5 muscarinic
      acetylcholine receptor knockout mice.
AB  - PURPOSE: To determine the functional role of M(3) and M(5) muscarinic
      acetylcholine receptor subtypes in ophthalmic arteries using gene-targeted mice.
      METHODS: Muscarinic receptor gene expression was quantified in murine ophthalmic
      arteries using real-time PCR. To test the functional relevance of M(3) and M(5)
      receptors, ophthalmic arteries from mice deficient in either subtype (M3R(-/-),
      M5R(-/-), respectively) and wild-type controls were isolated, cannulated with
      micropipettes, and pressurized. Changes in luminal vessel diameter in response to
      muscarinic and nonmuscarinic receptor agonists were measured by video microscopy.
      RESULTS: With the use of real-time PCR, all five muscarinic receptor subtypes
      were detected in ophthalmic arteries. However, mRNA levels of M(1), M(3), and
      M(5) receptors were higher than those of M(2) and M(4) receptors. In functional
      studies, after preconstriction with phenylephrine, acetylcholine and carbachol
      produced concentration-dependent dilations of ophthalmic arteries that were
      similar in M5R(-/-) and wild-type mice. Strikingly, cholinergic dilation of
      ophthalmic arteries was almost completely abolished in M3R(-/-) mice. Deletion of
      either M(3) or M(5) receptor did not affect responses to nonmuscarinic
      vasodilators such as bradykinin or nitroprusside. CONCLUSIONS: These findings
      provide the first evidence that M(3) receptors are critically involved in
      cholinergic regulation of diameter in murine ophthalmic arteries.

PMID- 19407020
TI  - The robustness of various forms of perimetry to different levels of induced
      intraocular stray light.
AB  - PURPOSE: To compare directly the robustness of standard automated perimetry
      (SAP), short-wavelength automated perimetry (SWAP), frequency-doubling perimetry
      (FDP), and grating-resolution perimetry (GRP) stimuli to different degrees of
      intraocular stray light induced by commercially available opacity-containing
      filters. METHODS: Five white opacity filters of increasing density were used to
      simulate the typical forward light scatter and stray light values associated with
      age-related lens opacification and significant cataract. The individually induced
      intraocular stray light value for each filter was quantified with a stray light
      meter and plotted against individual perimetric thresholds for the right eyes of
      three normally sighted trained observers for SAP, SWAP, FDP, and GRP. RESULTS:
      All tests were significantly but differently affected by increasing stray light.
      Overall average declines over a 1 log unit change in the stray light values were
      as follows: SAP, 4.85 dB; SWAP, 9.03 dB; FDP, 4.29 dB; and GRP, 1.36 dB.
      Standardized (z) scores were calculated after normalization to the spread of the
      normative data values for each instrument. These indicated that the standardized
      changes from baseline over the range of the five filters per log stray light unit
      were as follows: SAP, 2.177; SWAP, 1.96; FDP, 1.277; and GRP, 1.04. CONCLUSIONS:
      The increased stray light values induced by cataract-simulating filters has a
      significant effect on all tests. However, GRP, which is known to be limited by
      retinal sampling rather than contrast, remains the most robust of the tests to
      the effects of intraocular stray light. The degree to which the normative
      "sensitivity" range for different types of perimetry might incorporate a
      component caused by individual differences in intraocular stray light is
      discussed and requires further research.

PMID- 19407019
TI  - Light responses in rods of vitamin A-deprived Xenopus.
AB  - PURPOSE: Accumulation of free opsin by mutations in rhodopsin or insufficiencies
      in the visual cycle can lead to retinal degeneration. Free opsin activates
      phototransduction; however, the link between constitutive activation and retinal
      degeneration is unclear. In this study, the photoresponses of Xenopus rods
      rendered constitutively active by vitamin A deprivation were examined. Unlike
      their mammalian counterparts, Xenopus rods do not degenerate. Contrasting
      phototransduction in vitamin A-deprived Xenopus rods with phototransduction in
      constitutively active mammalian rods may provide new understanding of the
      mechanisms that lead to retinal degeneration. METHODS: The photocurrents of
      Xenopus tadpole rods were measured with suction electrode recordings, and
      guanylate cyclase activity was measured with the IBMX (3-isobutyl-1
      methylxanthine) jump technique. The amount of rhodopsin in rods was determined by
      microspectrophotometry. RESULTS: The vitamin A-deprived rod outer segments were
      60% to 70% the length and diameter of the rods in age-matched animals.
      Approximately 90% of its opsin content was in the free or unbound form. Analogous
      to bleaching adaptation, the photoresponses were desensitized (10- to 20-fold)
      and faster. Unlike bleaching adaptation, the vitamin A-deprived rods maintained
      near normal saturating (dark) current densities by developing abnormally high
      rates of cGMP synthesis. Their rate of cGMP synthesis in the dark (15 seconds(
      1)) was twofold greater than the maximum levels attainable by control rods (
      approximately 7 seconds(-1)). CONCLUSIONS: Preserving circulating current density
      and response range appears to be an important goal for rod homeostasis. However,
      the compensatory changes associated with vitamin A deprivation in Xenopus rods
      come at the high metabolic cost of a 15-fold increase in basal ATP consumption.

PMID- 19407021
TI  - CRB1 gene mutations are associated with keratoconus in patients with leber
      congenital amaurosis.
AB  - PURPOSE: To present an association of mutations in the CRB1 gene with keratoconus
      in patients with Leber congenital amaurosis (LCA). METHODS: Sixteen patients with
      genotyped LCA (having the CRB1, CRX, RetGC, RPE65, and AIPL1 mutations) were
      recruited from one ophthalmology practice and examined for the presence of
      keratoconus. Corneal topography, visual acuity, and slit lamp biomicroscopic
      examination were performed in all cases. RESULTS: The mean age of the patients
      was 34.5 years (range, 13-74). Visual acuities ranged from 20/40 to light
      perception. Corneal topography was successfully collected in 15 of the cases.
      Five of the 16 cases had slit lamp and/or topographic features consistent with
      keratoconus. One patient had a clinical picture that was keratoglobus-like. Of
      these six cases, four had a CRB1 mutation and two had a CRX mutation. Of the
      three subjects with the CRX mutation, one had keratoconus, one had the
      keratoglobus-like presentation, and one was normal. Our cohort represents 14
      separate, unrelated families. Only one family comprised multiple members with
      LCA. These were three affected brothers, one with keratoconus, all with CRB1
      mutations. CONCLUSIONS: Although the results cannot exclude other gene mutations,
      they suggest that LCA patients with a CRB1 mutation may have a particular
      susceptibility to keratoconus.

PMID- 19407023
TI  - The role of fractalkine as an accelerating factor on the autoimmune exocrinopathy
      in mice.
AB  - PURPOSE: Sjogren's syndrome (SS) is an organ-specific autoimmune disease caused
      by the progressive loss of exocrine glands and is associated with several
      autoimmune phenomena. Various research studies have been performed, and many
      molecules have been suggested as responsible for the pathogenesis of SS. Here the
      authors show the increased expression of fractalkine (CX(3)CL1) in lacrimal
      glands of SS model mice. Among more than 50 known chemokines, fractalkine is the
      sole member of the CX(3)C family and has unique structural and functional
      attributes. The purpose of this study was to analyze the role of fractalkine in
      exocrine glands. METHODS: The expression of fractalkine in the lacrimal glands of
      thymectomized NFS/sld mice was investigated by immunohistochemistry and RT-PCR.
      To confirm the effects of fractalkine in exocrine glands, tissue-specific
      fractalkine transgenic mice were generated using the salivary amylase promoter.
      RESULTS: The results demonstrated the upregulated fractalkine expression in
      thymectomized NFS/sld mice. Furthermore, the lacrimal and salivary gland-specific
      fractalkine transgenic mice showed the expression of fragmented fractalkine and
      lymphocytic infiltration in their lacrimal and submandibular glands.
      Interestingly, the dominant population was B cells in the lacrimal glands,
      whereas B cells and CD4(+) T cells were infiltrated in the submandibular glands.
      These mice also demonstrated slightly decreased tear and salivary secretion
      compared with wild-type mice. CONCLUSIONS: Based on these results, it may be that
      fractalkine contributes to the development of SS, especially in lymphocyte
      migration to exocrine glands, and that it accelerates the disease in association
      with other molecules.

PMID- 19407025
TI  - The relationship between diurnal variations in intraocular pressure measurements
      and central corneal thickness and corneal hysteresis.
AB  - PURPOSE: To examine the relationship between office-hour changes in IOP, measured
      with the Goldmann applanation tonometer (GAT) and dynamic contour tonometer
      (DCT), and the corneal characteristics central corneal thickness (CCT) and
      corneal hysteresis (CH). METHODS: Sixty-two eyes of 62 untreated normal subjects
      and patients with untreated glaucoma had IOP measurements performed with the GAT
      (mm Hg) and DCT (mm Hg) over an 8-hour period at 2-hour intervals beginning at 9
      AM. CCT (micrometers) was measured using a noncontact optical low-coherence
      reflectometry (OLCR) pachymeter, and CH (mm Hg) was measured with an ocular
      response analyzer (ORA). The associations between IOP measurements and corneal
      characteristics for each patient over the measurement period were assessed by
      using multilevel modeling. RESULTS: GAT and DCT IOP and CCT changed significantly
      during office hours (ANOVA; GAT: F = 19.9, P < 0.001; DCT: F = 4.6, P = 0.001;
      CCT: F = 16.4; P < 0.001). No significant changes were observed in CH (ANOVA; F =
      1.8, P = 0.13). Multilevel modeling analysis of the interrelationships between
      CCT, CH, and age on IOP measurements revealed that both CCT and CH changes were
      significantly associated with GAT IOP changes (GAT IOP/CCT slope, 0.04 mm
      Hg/microm; 95% confidence intervals [CIs], 0.02-0.06; GAT IOP/CH slope, 0.20 mm
      Hg/mm Hg; 95% CI, 0.01-0.39). CCT, but not CH, changes were significantly
      associated with DCT IOP changes (DCT IOP/CCT slope, 0.03 mm Hg/microm; 95% CI,
      0.00-0.05). However, although the association between CCT and GAT IOP was
      relatively uniform between subjects, association between CCT and DCT IOP showed
      greater intersubject variability. Age had no effect on the diurnal variation of
      IOP measured with either device. CONCLUSIONS: Measured IOP and corneal
      characteristics covary during office hours. Changes in CCT and CH are associated
      with changes in GAT IOP and, less consistently, with DCT IOP. The data suggest
      that variations in corneal characteristics explain a small proportion of the
      change in IOP measurements made with the GAT during office hours.

PMID- 19407024
TI  - The role of Bowman's layer in corneal regeneration after phototherapeutic
      keratectomy: a prospective study using in vivo confocal microscopy.
AB  - PURPOSE: To examine the role of Bowman's layer (BL) on the nature of anterior
      corneal regeneration after excimer laser phototherapeutic keratectomy (PTK).
      METHODS: A cohort of 13 patients underwent PTK to remove either 7 mum of BL for
      treatment of primary recurrent corneal erosions (RCE; six patients) or complete
      BL removal (15-mum ablation) to treat RCE or poor vision secondary to map-dot
      fingerprint (MDF) dystrophy (seven patients). Clinical examinations and laser
      scanning in vivo confocal microscopy (IVCM) were conducted before surgery and at
      a mean of 4 and 8 months after surgery. RESULTS: Total BL removal resulted in a
      significant decline in subbasal nerve density at 4 months (P = 0.007) that barely
      recovered to preoperative levels at 8 months (P = 0.055). With BL partially
      present, subbasal nerve density did not significantly change from preoperative
      levels. Superficial, wing, and basal epithelial cell density recovered to
      preoperative levels within 4 months after PTK, regardless of the presence of BL.
      Subepithelial keratocytes, however, were more densely distributed in corneas
      without BL relative to those with a partial BL present (P = 0.005), and increased
      anterior keratocyte reflectivity was noted in all eyes without BL and in no eye
      with a partial BL present. CONCLUSIONS: Subbasal nerve regeneration is delayed
      and subepithelial keratocyte density and reflectivity remain elevated up to 10
      months after total BL removal by PTK. The results provide initial evidence for a
      possible role of BL in facilitating rapid stromal wound healing and an associated
      recovery of anterior corneal transparency and the restoration of epithelial
      innervation after epithelial trauma.

PMID- 19407022
TI  - An altered phenotype in a conditional knockout of Pitx2 in extraocular muscle.
AB  - PURPOSE: To determine the temporal and spatial expression of Pitx2, a bicoid-like
      homeobox transcription factor, during postnatal development of mouse extraocular
      muscle and to evaluate its role in the growth and phenotypic maintenance of
      postnatal extraocular muscle. METHODS: Mouse extraocular muscles of different
      ages were examined for the expression of Pitx2 by RT-PCR, q-PCR, and
      immunostaining. A conditional mutant mouse strain, in which Pitx2 function is
      inactivated at postnatal day (P)0, was generated with a Cre-loxP strategy.
      Histology, immunostaining, real-time PCR, in vitro muscle contractility, and in
      vivo ocular motility were used to study the effect of Pitx2 depletion on
      extraocular muscle. RESULTS: All three Pitx2 isoforms were expressed by
      extraocular muscle and at higher levels than in other striated muscles.
      Immunostaining demonstrated the presence of Pitx2 mainly in extraocular muscle
      myonuclei. However, no obvious expression patterns were observed in terms of
      anatomic region (orbital versus global layer), innervation zone, or muscle fiber
      types. The mutant extraocular muscle had no obvious pathology but had altered
      muscle fiber sizes. Expression levels of myosin isoforms Myh1, Myh6, Myh7, and
      Myh13 were reduced, whereas Myh2, Myh3, Myh4, and Myh8 were not affected by
      postnatal loss of Pitx2. In vitro, Pitx2 loss made the extraocular muscles
      stronger, faster, and more fatigable. Eye movement recordings found saccades to
      have a lower peak velocity. CONCLUSIONS: Pitx2 is important in maintaining the
      mature extraocular muscle phenotype and regulating the expression of critical
      contractile proteins. Modulation of Pitx2 expression can influence extraocular
      muscle function with long-term therapeutic implications.

PMID- 19407026
TI  - Retrobulbar optic nerve diameter measured by high-speed magnetic resonance
      imaging as a biomarker for axonal loss in glaucomatous optic atrophy.
AB  - PURPOSE: To assess a novel magnetic resonance imaging (MRI) protocol for
      quantifying the optic nerve diameter (OND) as a measure of axonal loss in the
      optic nerve. METHODS: Included in the study was one eye each from 47 subjects, of
      whom 9 had no eye disease, 16 had preperimetric glaucoma, 11 had a glaucomatous
      mean visual field defect of <10 dB and 11 of >10 dB. Each subject underwent
      automated perimetry, scanning laser polarimetry, optic coherence tomography,
      scanning laser tomography, and ultrafast high-resolution MRI at 3 T. OND was
      determined 5, 10, and 15 mm behind the eye with a half Fourier-acquired single
      shot turbo spin-echo (HASTE)-sequence requiring 1.5 seconds of data acquisition
      time per slice and providing a spatial resolution of 0.11 mm. A multiple linear
      regression model was applied to determine correlations (r) among the different
      techniques. RESULTS: The correlation (r) was <0.37 for OND measurements taken 5
      mm behind the eye. At 10 mm behind the eye, r increased to 0.57 and was
      statistically significant in four out six instances. In the orbital apex 15 mm
      behind the eye, r reached a maximum of 0.80 and was statistically significant in
      all instances. OND correlated best with the retinal nerve fiber layer thickness
      measured by optic coherence tomography. CONCLUSIONS: Retina- or optic nerve head
      related surrogate markers for axonal content correlated closely with the OND,
      although only when it was measured in the orbital apex. High-resolution MRI using
      an ultrafast HASTE-sequence at 3 T proved useful for OND quantification and may
      be a valuable asset in future neuroprotection trials.

PMID- 19407027
TI  - Sirt1 involvement in rd10 mouse retinal degeneration.
AB  - PURPOSE: Sirtuin1 (Sirt1) is an NAD(+)-dependent deacetylase involved in
      development, cell survival, stress resistance, energy metabolism, and aging. It
      is expressed in the mammalian central nervous system (CNS) and is activated
      during processes associated with neuroprotection. The retinal degeneration 10
      (rd10) mouse model of retinitis pigmentosa (RP) was used to investigate the
      possible role of Sirt1 in this type of retinal degeneration. METHODS: Eyes from
      control and rd10 mice were used. Sirt1 mRNA was detected by in situ
      hybridization, and its abundance was estimated by semiquantitative RT-PCR. The
      presence of Sirt1 protein was investigated by immunohistofluorescence and Western
      blot analysis. The apoptosis of photoreceptor cells was analyzed by terminal dUTP
      transferase nick-end labeling (TUNEL). Immunolabeling for Sirt1, apoptosis
      inducing factor (Aif), and caspase-12 (Casp-12) was performed on retinal tissue
      sections. RESULTS: Sirt1 mRNA and immunoreactivity were observed in normal adult
      mouse eyes. In the control retina, Sirt1 was immunolocalized mostly to the
      nucleus. In rd10 mice with retinal degeneration, changes in Sirt1 immunolabeling
      were observed only in the retinal outer nuclear layer (ONL). The pathologic
      pattern of Sirt1 immunoreactivity correlated with the start of retinal
      degeneration in rd10 mice. CONCLUSIONS: The results suggest a link between Sirt1
      production and retinal degeneration in rd10 mice. The anti-apoptotic,
      neuroprotective role of Sirt1 in the mouse retina is based on the involvement of
      Sirt1 in double DNA strand-break repair mechanisms and in maintaining energy
      homeostasis in photoreceptor cells. The results suggest that the neuroprotective
      properties of Sirt1 may gradually weaken in rd10 mouse photoreceptor cells.

PMID- 19407029
TI  - Transparency, accountability and vaccination policy.

PMID- 19407031
TI  - Attorney General forces Infectious Diseases Society of America to redo Lyme
      guidelines due to flawed development process.
AB  - Lyme disease is one of the most controversial illnesses in the history of
      medicine. In 2006 the Connecticut Attorney General launched an antitrust
      investigation into the Lyme guidelines development process of the Infectious
      Diseases Society of America (IDSA). In a recent settlement with IDSA, the
      Attorney General noted important commercial conflicts of interest and suppression
      of scientific evidence that had tainted the guidelines process. This paper
      explores two broad ethical themes that influenced the IDSA investigation. The
      first is the growing problem of conflicts of interest among guidelines
      developers, and the second is the increasing centralisation of medical decisions
      by insurance companies, which use treatment guidelines as a means of controlling
      the practices of individual doctors and denying treatment for patients. The
      implications of the first-ever antitrust investigation of medical guidelines and
      the proposed model to remediate the tainted IDSA guidelines process are also
      discussed.

PMID- 19407030
TI  - Under what conditions do patients want to be informed about their risk of a
      complication? A vignette study.
AB  - BACKGROUND: Discussing treatment risks has become increasingly important in
      medical communication. Still, despite regulations, physicians must decide how
      much and what kind of information to present. OBJECTIVE: To investigate patients'
      preference for information about a small risk of a complication of colonoscopy,
      and whether medical and personal factors contribute to such preference. To
      propose a disclosure policy related to our results. DESIGN: Vignettes study.
      SETTING: Department of Gastroenterology, Academic Medical Centre, the
      Netherlands. PATIENTS: 810 consecutive colonoscopy patients. INTERVENTION: A home
      sent questionnaire containing three vignettes. Vignettes varied in the indication
      for colonoscopy, complication severity and level of risk. Patients were invited
      to indicate their wish to be informed and the importance of such information. In
      addition, sociodemograhic, illness-related and psychological characteristics were
      assessed. MAIN OUTCOME MEASUREMENTS: Wish to be informed and importance of
      information. RESULTS: Of 810 questionnaires, 68% were returned. Patients
      generally wished to be informed about low-risk complications, regardless of the
      indication for colonoscopy or the severity of the complication. The level of risk
      did matter, though (OR = 2.48, SE = 0.28, p = 0.001). The information was
      considered less important if done for population screening purposes or diagnosis
      of colon cancer, if the complication was less severe (bleeding) and if the risk
      was smaller (0.01% and 0.1%). Patients' information preference was also related
      to age, mood and coping style. LIMITATIONS: Difficulty of vignettes. CONCLUSIONS:
      Patients generally wish to be informed about all possible risks. However, this
      might become uninformative. A stepwise approach is suggested.

PMID- 19407032
TI  - Stimulating brains, altering minds.
AB  - Deep-brain stimulation has been used to treat advanced Parkinson disease and
      other neurological and psychiatric disorders that have not responded to other
      treatments. While deep-brain stimulation can modulate overactive or underactive
      regions of the brain and thereby improve motor function, it can also cause
      changes in a patient's thought and personality. This paper discusses the trade
      offs between the physiological benefit of this technique and the potential
      psychological harm.

PMID- 19407033
TI  - Positing a difference between acts and omissions: the principle of justice,
      Rachels' cases and moral weakness.
AB  - The difficulty in discovering a difference between killing and letting die has
      led many philosophers to deny the distinction. This paper seeks to develop an
      argument defending the distinction between killing and letting die. In relation
      to Rachels' cases, the argument is that (a) even accepting that Smith and Jones
      may select equally heinous options from the choices they have available to them,
      (b) the fact that the choices available to them are different is morally
      relevant, and (c) this difference in available choices can be used to distinguish
      between the agents in certain circumstances. It is the principle of justice, as
      espoused by Aristotle, which requires that equal things are treated equally and
      that unequal things are treated unequally that creates a presumption that Smith
      and Jones should be treated differently. The magnitude of this difference can be
      amplified by other premises, making the distinction morally relevant in practical
      reality.

PMID- 19407034
TI  - "You can't handle the truth"; medical paternalism and prenatal alcohol use.
AB  - The publication of the latest contribution to the alcohol-in-pregnancy debate,
      and the now customary flurry of media attention it generated, have precipitated
      the renewal of a series of ongoing debates about safe levels of consumption and
      responsible prenatal conduct. The University College London (UCL) study's finding
      that low levels of alcohol did not contribute to adverse behavioural outcomes-and
      may indeed have made a positive contribution in some cases-is unlikely to be the
      last word on the subject. Proving a negative correlation is notoriously difficult
      (technically, impossible), and other studies have offered alternative claims. The
      author is not an epidemiologist, and the purpose of this article is not to
      evaluate the competing empirical claims. However, the question of what
      information and advice healthcare practitioners ought to present to pregnant
      women, or prospectively or potentially pregnant women, in a situation of
      uncertainty is one to which healthcare ethicists may have a contribution to make.
      In this article, it is argued that the total abstinence policy advocated by the
      UK's Department of Health, and even more stridently by the British Medical
      Association, sits uneasily with recent data and is far from ethically
      unproblematic. In particular, the "precautionary" approach advocated by these
      bodies displays both scant regard for the autonomy of pregnant and prospectively
      pregnant women and a confused grasp of the principles of beneficence and non
      maleficence.

PMID- 19407035
TI  - Abortion: Strong's counterexamples fail.
AB  - This paper shows that the counterexamples proposed by Strong in 2008 in the
      Journal of Medical Ethics to Marquis's argument against abortion fail. Strong's
      basic idea is that there are cases--for example, terminally ill patients--where
      killing an adult human being is prima facie seriously morally wrong even though
      that human being is not being deprived of a "valuable future". So Marquis would
      be wrong in thinking that what is essential about the wrongness of killing an
      adult human being is that they are being deprived of a valuable future. This
      paper shows that whichever way the concept of "valuable future" is interpreted,
      the proposed counterexamples fail: if it is interpreted as "future like ours",
      the proposed counterexamples have no bearing on Marquis's argument. If the
      concept is interpreted as referring to the patient's preferences, it must be
      either conceded that the patients in Strong's scenarios have some valuable future
      or admitted that killing them is not seriously morally wrong. Finally, if
      "valuable future" is interpreted as referring to objective standards, one ends up
      with implausible and unpalatable moral claims.

PMID- 19407037
TI  - Ethical issues in funding research and development of drugs for neglected
      tropical diseases.
AB  - Neglected and tropical diseases, pervasive in developing countries, are important
      contributors to global health inequalities. They remain largely untreated due to
      lack of effective and affordable treatments. Resource-poor countries cannot
      afford to develop the public health interventions needed to control neglected
      diseases. In addition, neglected diseases do not represent an attractive market
      for pharmaceutical industry. Although a number of international commitments,
      stated in the Millennium Development Goals, have been made to avert the risk of
      communicable diseases, tropical diseases still remain neglected due to delays in
      international assistance. This delay can be explained by the form international
      cooperation has generally taken, which is limited to promoting countries'
      national interests, rather than social justice at a global level. This restricts
      the international responsibility for global inequalities in health to a
      humanitarian assistance. We propose an alternative view, arguing that expanding
      the scope of international cooperation by promoting shared health and economic
      value at a global level will create new opportunities for innovative, effective
      and affordable interventions worldwide. It will also promote neglected diseases
      as a global research priority. We build our argument on a proposal to replace the
      patenting system that currently regulates pharmaceutical research with a global
      fund to reward this research based on actual decreases in morbidity and mortality
      at a global level. We argue that this approach is beneficent because it will
      decrease global health inequalities and promote social justice worldwide.

PMID- 19407036
TI  - Is there a duty to share genetic information?
AB  - A number of prominent bioethicists, such as Parker, Lucassen and Knoppers, have
      called for the adoption of a system in which by default genetic information is
      shared among family members. This paper suggests that a main reason given in
      support of this call to share genetic information among family members is the
      idea that genetic information is essentially familial in nature. On examining
      this "familial nature of genetics" argument, the paper shows that most genetic
      information is only shared in a weaker way among family members and does not
      necessarily lead to the actual manifestation of particular diseases. The upshot
      is that the idea that genetic information is familial in nature does not provide
      sufficient ground for moving towards a system in which by default genetic
      information is shared among family members.

PMID- 19407038
TI  - Paying a high price for low costs: why there should be no legal constraints on
      the profits that can be made on drugs for tropical diseases.
AB  - This paper deals with the question of how to price drugs for tropical diseases.
      The thesis defended in the paper is: (i) there should be no legal constraints on
      the profits pharmaceutical companies can make on their products for tropical
      diseases. In essence, (i) expresses the idea that drugs for tropical diseases
      should be treated as any other product on the free market and that the producers
      of these drugs should be allowed to sell their products at whatever price the
      market can bear. The main argument in favour of (i) is first outlined. Five
      common arguments against (i) are thereafter discussed, and it is argued that all
      of these fail in their intended purpose.

PMID- 19407039
TI  - Iran's experience with surrogate motherhood: an Islamic view and ethical
      concerns.
AB  - Gestational surrogacy as a treatment for infertility is being practised in some
      well-known medical institutions in Tehran and some other cities in Iran. While
      the majority of Muslims in the world are Sunni, the majority of Iranians are
      Shiite. Most Sunni scholars do not permit surrogate motherhood, since it involves
      introducing the sperm of a man into the uterus of a woman to whom he is not
      married. Most Shiite scholars, however, have issued jurisprudential decrees
      (fatwas) that allow surrogate motherhood as a treatment for infertility, albeit
      only for legal couples. They regard this practice as transferring an embryo or
      fetus from one womb to another, which is not forbidden in Shiite jurisprudence.
      Nevertheless, there are some controversies concerning some issues such as kinship
      and inheritance. The main ethical concern of Iran's experience with gestational
      surrogacy is the monetary relation between the intended couple and the surrogate
      mother. While monetary remuneration is practised in Iran and allowed by religious
      authorities, it seems to suffer from ethical problems. This article proposes that
      this kind of monetary relation should be modified and limited to reimbursement of
      normal costs. Such modification requires new legislation and religious decrees.

PMID- 19407040
TI  - Erring on the side of life: the case of Terri Schiavo.
AB  - In debates over life and death it is often said that one should err on the side
      of caution--that is, on the side of life. In the light of the recent case of
      Terri Schiavo, it is explained how the "err-on-the-side-of-life" argument
      proceeds, and an objection to it is offered.

PMID- 19407042
TI  - Grim news for an unoriginal position: a reply to Seth Baum.
AB  - Seth Baum suggests that my claim that it is better never to come into existence
      "can readily be rejected not just out of reflexive distaste for the claim but
      also out of sound ethical reasoning". In my reply, I argue that Mr Baum fails to
      state accurately what my arguments are, and then attempts to refute them by
      association with other views that he dismisses perfunctorily. Where he does
      actually engage in my views, his response is effectively merely to assert the
      opposite.

PMID- 19407043
TI  - Resource expenditure not resource allocation: response to McDougall on cloning
      and dignity.
AB  - This paper offers some comments on bioethical debates about resource allocation
      in healthcare. It is stimulated by Rosalind McDougall's argument that it is an
      affront to the human dignity of people with below "liberties-level" health to
      fund human reproductive cloning. McDougall is right to underline the relevance of
      resource prioritisation to the ethics of research and provision of new biomedical
      technologies. This paper argues that bioethicists should be careful when offering
      comments about such issues. In particular, it emphasises the need to represent
      accurately the reality of the situation-especially when we are passing judgement
      on technologies that are in their infancy and whose practical application is yet
      to be confirmed. The paper also emphasises the importance of the actual context
      to bioethical debate, and note that it would be better to talk about resource
      expenditure rather than resource allocation when it comes to discussing the
      rights and wrongs of how money is spent. It also reiterates the claims made by
      other writers that social and political philosophy need to have a transparent and
      considered role in debates about resources.

PMID- 19407044
TI  - Nutritional rehabilitation: from pulmonary cachexia to sarcoPD.

PMID- 19407045
TI  - Hospital-acquired pneumonia in Europe.

PMID- 19407046
TI  - Quality of life, stage severity and COPD.

PMID- 19407047
TI  - LTBI: latent tuberculosis infection or lasting immune responses to M.
      tuberculosis? A TBNET consensus statement.
AB  - Tuberculosis control relies on the identification and preventive treatment of
      individuals who are latently infected with Mycobacterium tuberculosis. However,
      direct identification of latent tuberculosis infection is not possible. The
      diagnostic tests used to identify individuals latently infected with M.
      tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-gamma
      release assays (IGRAs), are designed to identify an adaptive immune response
      against, but not necessarily a latent infection with, M. tuberculosis. The
      proportion of individuals who truly remain infected with M. tuberculosis after
      tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long
      adaptive immune responses towards mycobacterial antigens persist in the absence
      of live mycobacteria. Clinical management and public healthcare policies for
      preventive chemotherapy against tuberculosis could be improved, if we were to
      gain a better understanding on M. tuberculosis latency and reactivation. This
      statement by the TBNET summarises knowledge and limitations of the currently
      available tests used in adults and children for the diagnosis of latent
      tuberculosis infection. In summary, the main issue regarding testing is to
      restrict it to those who are known to be at higher risk of developing
      tuberculosis and who are willing to accept preventive chemotherapy.

PMID- 19407048
TI  - Prevalence of residual excessive sleepiness in CPAP-treated sleep apnoea
      patients: the French multicentre study.
AB  - The percentage of compliant continuous positive airway pressure (CPAP)-treated
      apnoeic patients that continue to experience residual excessive sleepiness (RES)
      is unknown. RES was defined by an Epworth Sleepiness Scale (ESS) score of >or=11.
      In total, 502 patients from 37 French sleep centres using CPAP >3 h night(-1)
      attending their 1-yr follow-up visit were eligible. ESS and polysomnographic data
      as well as symptoms, quality of life, depression scores and objective CPAP
      compliance at 1 yr were collected. Overall, 60 patients remained sleepy on CPAP
      (ESS 14.3+/-2.5) leading to a prevalence rate of RES of 12.0% (95% confidence
      interval (CI) 9.1-14.8). After having excluded associated restless leg syndrome,
      major depressive disorder and narcolepsy as confounding causes, the final
      prevalence rate of RES was 6.0% (95% CI 3.9-8.01). Patients with RES were younger
      and more sleepy at diagnosis. The relative risk of having RES was 5.3 (95% CI 1.6
      22.1), when ESS before treatment was >or=11. Scores of emotional and energy
      Nottingham Health Profile domains were two times worse in patients with RES. As
      230,000 obstructive sleep apnoea patients are currently treated in France by
      continuous positive airway pressure, more than 13,800 of them might suffer from
      residual excessive sleepiness.

PMID- 19407049
TI  - Outpatient treatment and early discharge of symptomatic pulmonary embolism: a
      systematic review.
AB  - The published literature regarding the safety of outpatient treatment of
      symptomatic pulmonary embolism (PE) was systematically summarised. A literature
      search was performed using the PubMed and EMBASE databases. Studies in which
      patients had symptomatic PE and the antithrombotic treatment was administered
      completely at home or the patients were discharged early were selected. A scoring
      system was used to divide studies into three quality categories. Short- and long
      term outcomes were extracted: all-cause mortality, death from PE or from major
      haemorrhage, recurrent venous thromboembolism, and major bleeding. Eleven
      observational studies were included. No randomised controlled studies were
      identified. No study fulfilled the criteria for high quality. A total of 928
      patients with symptomatic PE were treated completely as outpatients or discharged
      early; haemodynamic instability and hypoxia were the main exclusion criteria. No
      patient died during the first 7 days of antithrombotic treatment. Outpatient
      treatment of symptomatic PE is not based on high-quality evidence. Although the
      published data suggest that certain subgroups of haemodynamically and
      respiratorily stable patients may be safely treated at home when a well-defined
      management programme is applied, further studies are warranted for a short-term
      prognostic risk stratification of this PE subgroup.

PMID- 19407050
TI  - Effectiveness and safety of endobronchial ultrasound-transbronchial needle
      aspiration: a systematic review.
AB  - The aim of the present systematic review was to assess the effectiveness and
      safety of real time endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) in patients with suspected or known bronchopulmonary
      carcinoma, as well as in other clinical indications presented by lymphatic
      adenopathies. A systematic review was carried out in November 2007 and updated in
      April 2008 using the main databases. Inclusion and exclusion criteria were
      applied to the papers retrieved. A total of 20 publications were included. Of
      these, 14 were original studies that investigated the clinical usefulness of the
      technique in visualising and staging lymph nodes in patients with suspected or
      established lung cancer. Sensitivity ranged 85-100% and negative predictive value
      ranged 11-97.4%. Three studies assessed the clinical usefulness of the technique
      in the diagnosis of sarcoidosis. EBUS-TBNA was diagnostic in 88-93% of patients.
      One retrospective study evaluated the use of EBUS-TBNA in the diagnosis of
      lymphoma. None of the studies included in the present review reported important
      complications. Endobronchial ultrasound-guided transbronchial needle aspiration
      is a safe and highly accurate procedure for the examination and staging of
      mediastinal and hilar lymph nodes in patients with known or suspected lung
      malignancy. The evidence is promising for sarcoidosis but is not sufficient for
      lymphoma.

PMID- 19407051
TI  - Systemic manifestations and comorbidities of COPD.
AB  - Increasing evidence indicates that chronic obstructive pulmonary disease (COPD)
      is a complex disease involving more than airflow obstruction. Airflow obstruction
      has profound effects on cardiac function and gas exchange with systemic
      consequences. In addition, as COPD results from inflammation and/or alterations
      in repair mechanisms, the "spill-over" of inflammatory mediators into the
      circulation may result in important systemic manifestations of the disease, such
      as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate
      or worsen comorbid diseases, such as ischaemic heart disease, heart failure,
      osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid
      diseases potentiate the morbidity of COPD, leading to increased hospitalisations,
      mortality and healthcare costs. Comorbidities complicate the management of COPD
      and need to be evaluated carefully. Current therapies for comorbid diseases, such
      as statins and peroxisome proliferator-activated receptor-agonists, may provide
      unexpected benefits for COPD patients. Treatment of COPD inflammation may
      concomitantly treat systemic inflammation and associated comorbidities. However,
      new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4
      inhibitors, have significant side-effects so it may be necessary to develop
      inhaled drugs in the future. Another approach is the reversal of corticosteroid
      resistance, for example with effective antioxidants. More research is needed on
      COPD comorbidities and their treatment.

PMID- 19407052
TI  - The pulmonary vascular complications of hereditary haemorrhagic telangiectasia.
AB  - Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant
      disorder, characterised by the presence of vascular malformations. The pulmonary
      vascular complications of HHT include pulmonary arteriovenous malformations,
      pulmonary hypertension associated with high-output heart failure and liver
      vascular malformations and, finally, pulmonary arterial hypertension secondary to
      HHT. In the present review, the authors describe the clinical presentation,
      diagnosis and management of all three pulmonary vascular presentations of HHT, as
      well as the underlying genetics and pathophysiology.

PMID- 19407053
TI  - Cardiovascular disease in obstructive sleep apnoea syndrome: the role of
      intermittent hypoxia and inflammation.
AB  - There is increasing evidence that intermittent hypoxia plays a role in the
      development of cardiovascular risk in obstructive sleep apnoea syndrome (OSAS)
      through the activation of inflammatory pathways. The development of translational
      models of intermittent hypoxia has allowed investigation of its role in the
      activation of inflammatory mechanisms and promotion of cardiovascular disease in
      OSAS. There are noticeable differences in the response to intermittent hypoxia
      between body tissues but the hypoxia-sensitive transcription factors hypoxia
      inducible factor-1 and nuclear factor-kappaB appear to play a key role in
      mediating the inflammatory and cardiovascular consequences of OSAS. Expanding our
      understanding of these pathways, the cross-talk between them and the activation
      of inflammatory mechanisms by intermittent hypoxia in OSAS will provide new
      avenues of therapeutic opportunity for the disease.

PMID- 19407054
TI  - Pre-operative pulmonary evaluation of lung cancer patients: a review of the
      literature.
AB  - Complete anatomical resection of the primary tumour is still the standard of care
      in patients with early stage lung cancer. Because these patients are usually
      smokers who also suffer from chronic obstructive pulmonary disease, regional
      differences in pulmonary function due to lung tissue destruction exist. The
      purpose of the present article is to evaluate the currently available guidelines
      and to discuss novel methods for the pre-operative functional and anatomical
      pulmonary evaluation in lung cancer patients. Despite the fact that knowledge on
      the pre-operative evaluation of the pulmonary function has substantially
      increased during the past decade, the majority of the studies are small,
      underpowered and, with exception of a proposed algorithm, not prospectively
      validated in independent cohorts. The future harmonisation of guidelines is
      required and novel imaging techniques should be incorporated in the pre-operative
      evaluation in chronic obstructive pulmonary disease patients with borderline
      pulmonary function.

PMID- 19407055
TI  - Unusual microbes in asthma exacerbation: Alcaligenes xylosoxidans and Leishmania.
AB  - Asthma is a chronic inflammatory condition characterised by a variable degree of
      airflow limitation. Exacerbations during the course of asthma often occur due to
      environmental factors or infectious, mostly viral, aetiology. The present study
      reports the case of a 61-yr-old male with severe asthma hospitalised due to
      increasing respiratory distress. Since recovery was delayed despite anti
      obstructive/anti-inflammatory and antibiotic therapy, further diagnostic
      procedures, including bronchoscopy, were performed in order to attempt to
      identify the cause of the worsening respiratory condition. The surprising finding
      consisted of a rare coincidence of concomitant infection with the bacterial
      pathogen Alcaligenes xylosoxidans, grown from bronchoalveolar lavage fluid, and
      the protozoan parasite Leishmania spp., revealed by histopathological examination
      of bronchial mucosal biopsy specimens. This is the first report of an isolated
      bronchial mucosal involvement of Leishmania in an HIV-negative asthma patient
      following brief exposure in Leishmania-endemic regions. Further, to the best of
      the present authors' knowledge, this represents the first description of A.
      xylosoxidans in asthma, although it is questionable whether it was an infection
      or colonisation. The present observation identifies previously unreported
      microbial pathogens associated with asthma exacerbation. Further, the report
      highlights the importance of obtaining a thorough travel history and applying
      invasive diagnostic procedures in circumstances of treatment failure, even under
      unfavourable conditions.

PMID- 19407056
TI  - Plasmapheresis for treatment of pulmonary alveolar proteinosis.
AB  - Whole lung lavage (WLL) is currently the standard therapy for pulmonary alveolar
      proteinosis (PAP). Nevertheless, some PAP patients respond poorly to WLL or
      require it frequently. The present paper reports a patient with autoimmune PAP
      with persistent disease despite three WLL treatments over 10 months.
      Plasmapheresis with ten 1.5-L plasma exchanges was performed, which lowered the
      serum granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody
      level from 250 microg mL(-1) to 156 microg mL(-1) but did not improve respiratory
      impairment. Further WLL therapy was required and transiently effective. Serum GM
      CSF autoantibody levels declined progressively, reaching a value of 56 microg mL(
      1) 80 weeks after completion of plasmapheresis. However, this decrease was not
      accompanied by clinical improvement and the patient required additional WLL
      therapy. The results confirm that minor reductions in serum granulocyte
      macrophage colony-stimulating factor autoantibody levels from plasmapheresis are
      not reflected in clinical improvement in the severity of lung disease in
      pulmonary alveolar proteinosis.

PMID- 19407057
TI  - Consort hypersensitivity pneumonitis.
AB  - To date, there is little information in the literature that hypersensitivity
      pneumonitis due to birds may occur without direct contact to birds. A 62-yr-old
      pensioner developed mild flu-like symptoms, fatigue and polyuria several hours
      after each meeting with his new female partner, either in hotels or his
      apartment. After divorcing from her ex-husband, who was a canary fancier, the
      female had moved into a bungalow approximately 6 months earlier. When the couple
      met for the first time at the bungalow, the patient's symptoms worsened and he
      developed shortness of breath. The patient had never entered the bird house or
      the married couple's house. Hypersensitivity pneumonitis was demonstrated by
      chest radiography, computed tomography, a restrictive ventilatory defect,
      decreased diffusion capacity and hypoxaemia after physical exercise.
      Sensitisation to canaries was shown by immunoassays. Canary antigens were
      detected by a polyclonal immunoassay at different locations of the married
      couple's house and the female's bungalow, where no birds had ever been kept. In
      conclusion, hypersensitivity pneumonitis should be recognised as a further
      consort disease, i.e. a disease that can be transmitted by partners.

PMID- 19407058
TI  - An incidental finding in a 34-year-old male under investigation for haemoptysis.
      Diagnosis: The radiological and endoscopic images demonstrate a complex defect
      along the posterior tracheal wall consistent with acquired tracheal diverticulum.

PMID- 19407059
TI  - A 61-year-old female patient with right-sided pleuritic chest pain and fatigue.
      Diagnosis: Inflammatory pseudotumour causing right pulmonary artery occlusion
      with subsequent infarction of the lung.

PMID- 19407060
TI  - Does PDE4 inhibition improve alveolarisation in hyperoxia-exposed immature
      rodents?

PMID- 19407061
TI  - Exhaled breath condensates and COPD.

PMID- 19407062
TI  - Macrolide therapy in asthma: limited treatment, long-term improvement.

PMID- 19407063
TI  - Obesity: mediators and treatment approaches.

PMID- 19407064
TI  - Association between the connexin37 polymorphism and peripheral arterial disease
      in subjects with type 2 diabetes.

PMID- 19407065
TI  - Cumulative effect of oxidative stress-related gene polymorphisms on myocardial
      infarction in type 2 diabetes.

PMID- 19407066
TI  - Depression and type 2 diabetes over the lifespan: a meta-analysis. Response to
      Mezuk et al.

PMID- 19407068
TI  - Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for
      the initiation and adjustment of therapy: a consensus statement of the American
      Diabetes Association and the European Association for the Study of Diabetes.
      Response to Nathan et al.

PMID- 19407070
TI  - Predicting 6-year mortality risk in patients with type 2 diabetes: response to
      Wells et al.

PMID- 19407072
TI  - Prevalence and control of diabetes and impaired fasting glucose in New York City:
      response to Thorpe et al.

PMID- 19407074
TI  - Diabetic subjects diagnosed through the Diabetes Prevention Trial-Type 1 (DPT-1)
      are often asymptomatic with normal A1C at diabetes onset.
AB  - OBJECTIVE: Upon diagnosis of type 1 diabetes, patients are usually symptomatic,
      and many have ketoacidosis. Screening for islet autoantibodies (IAs) has been
      shown to decrease A1C level and rate of hospitalization at diabetes onset.
      Metabolic tests and the presence of symptoms were described at diabetes onset
      during the Diabetes Prevention Trial-Type 1 (DPT-1). RESEARCH DESIGN AND METHODS:
      The DPT-1 screened relatives of patients with type 1 diabetes for islet cell
      autoantiobodies (ICAs). Those with positive ICAs had intravenous and oral glucose
      tolerance tests (IVGTTs and OGTTs) and were randomized into one of two prevention
      trials. Throughout the DPT-1 parenteral and oral insulin study, 246 people were
      diagnosed with type 1 diabetes. RESULTS: Of the 246 subjects diagnosed with
      diabetes, 218 had data regarding the presence of symptoms, and 138 (63.3%)
      reported no symptoms suggestive of diabetes. Eight subjects (3.67%) presented
      with ketosis. Subjects presented with a mean +/- SD A1C of 6.41 +/- 1.15%. At
      diagnosis, 90 subjects (50.8%) had A1C in the normal range (<6.2%). OGTT data at
      the time of diagnosis indicate that 35.4% had a glucose result of <100 mg/dl at 0
      min. CONCLUSIONS: The majority of subjects diagnosed with type 1 diabetes through
      the DPT-1 were asymptomatic at onset and had normal fasting glucose and A1C
      levels. This suggests that intermittent screening (IA followed by OGTT) may allow
      diagnosis of diabetes before severe metabolic decompensation. Screening with A1C
      will miss identifying many of the subjects with newly diagnosed type 1 diabetes
      in this cohort.

PMID- 19407075
TI  - Sexual dysfunction in women with type 1 diabetes: long-term findings from the
      DCCT/ EDIC study cohort.
AB  - OBJECTIVE: This study aimed to investigate the prevalence and risk factors
      associated with sexual dysfunction in a well-characterized cohort of women with
      type 1 diabetes. RESEARCH DESIGN AND METHODS: The study was conducted in women
      enrolled in the long-term Epidemiology of Diabetes Interventions and
      Complications (EDIC) study, a North American study of men and women with type 1
      diabetes. At year 10 of the EDIC study, 652 female participants were invited to
      complete a validated self-report measure of sexual function, standardized history
      and physical examinations, laboratory testing, and mood assessment. RESULTS: Of
      the sexually active women with type 1 diabetes in the EDIC study, 35% met
      criteria for female sexual dysfunction (FSD). Women with FSD reported loss of
      libido (57%); problems with orgasm (51%), lubrication (47%), and arousal (38%);
      and pain (21%). Univariate analyses revealed a positive association between FSD
      and age (P = 0.0041), marital status (P = 0.0016), menopausal status (P =
      0.0019), microvasculopathy (P = 0.0092), and depression (P = 0.0022). However, in
      a multivariate analysis, only depression (P = 0.004) and marital status (P =
      0.003) were significant predictors of FSD. CONCLUSIONS: FSD is common in women
      with type 1 diabetes and affects all aspects of sexual function and satisfaction.
      Depression is the major predictor of sexual dysfunction in women with type 1
      diabetes. These findings suggest that women with type 1 diabetes should be
      routinely queried about the presence of sexual dysfunction and possible co
      association with depression.

PMID- 19407076
TI  - Influence of fat and carbohydrate proportions on the metabolic profile in
      patients with type 2 diabetes: a meta-analysis.
AB  - OBJECTIVE: The effects of dietary macronutrient composition on metabolic profiles
      in patients with type 2 diabetes have been inconsistent. This meta-analysis aimed
      to elucidate the effect of replacing dietary fat with carbohydrate on glucose and
      lipid parameters in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS:
      We searched for randomized trials that investigated the effects of two kinds of
      prescribed diets (a low-fat, high-carbohydrate [LFHC] diet and a high-fat, low
      carbohydrate [HFLC] diet); in these studies, energy and protein intake did not
      differ significantly between the two dietary groups. Nineteen studies that
      included 306 patients met our inclusion criteria. Median diet composition of
      carbohydrate/fat in the LFHC and HFLC diets was 58%/24% and 40%/40%,
      respectively. RESULTS: Changes in values for A1C, fasting plasma glucose (FPG),
      and total and LDL cholesterol did not differ significantly between the LFHC and
      HFLC groups. However, the LFHC diet significantly increased fasting insulin and
      triglycerides by 8% (P = 0.02) and 13% (P < 0.001), respectively, and lowered HDL
      cholesterol by 6% (P < 0.001) compared with the HFLC diet. There were positive
      associations among the magnitude of changes in FPG, fasting insulin, and
      triglycerides for the diets analyzed. However, stratified analysis indicated that
      the increase in triglycerides was insignificant when accompanied by energy intake
      restriction. CONCLUSIONS: Our findings suggested that replacing fat with
      carbohydrate could deteriorate insulin resistance while the adverse effect on
      triglycerides from the LFHC diet could be avoided by restricting energy intake to
      a degree sufficient for the attainment of weight reduction.

PMID- 19407077
TI  - Is it time to take a different approach to screening people at high risk for type
      1 diabetes?

PMID- 19407078
TI  - Building a National Health IT System from the middle out.

PMID- 19407081
TI  - Blood chimerism confounds genetic relative susceptibility testing for classical
      scrapie in sheep.
AB  - Classical scrapie disease is a transmissible spongiform encephalopathy of sheep
      that is enzootic in the United States. Susceptibility of sheep to classical
      scrapie is linked to single nucleotide polymorphisms in the prion protein gene
      (PRNP), forming the basis for genetic testing strategies used by national efforts
      to eradicate scrapie. Such efforts are occasionally hampered by inconclusive
      results stemming from the detection of "complex" genotypes. Naturally occurring
      cases of ovine chimerism are thought to account for some of these instances. In
      the current report, 4 naturally occurring ovine chimeras are documented through
      cytogenetic and molecular analyses. All 4 of these sheep had chimeric cells
      circulating in their blood. Blood and alternate tissue samples of ear punch and
      hair bulbs from one of these chimeras was submitted in batch with similar samples
      from control sheep for routine scrapie genetic relative susceptibility testing. A
      complex PRNP genotype was detected in the blood of the chimeric female but not in
      the alternate tissue samples or in the control sheep samples. The results
      demonstrate that naturally occurring blood chimerism can confound current testing
      efforts. The potential impacts of undetected chimeras on current scrapie
      eradication efforts are discussed.

PMID- 19407082
TI  - Systemic iridovirus infection in the Banggai cardinalfish (Pterapogon kauderni
      Koumans 1933).
AB  - Iridoviruses infect food and ornamental fish species from a wide range of
      freshwater to marine habitats across the globe. The objective of the current
      study was to characterize an iridovirus causing systemic infection of wild-caught
      Pterapogon kauderni Koumans 1933 (Banggai cardinalfish). Freshly frozen and fixed
      specimens were processed for histopathologic evaluation, transmission electron
      microscopic examination, virus culture, molecular virologic testing,
      microbiology, and in situ hybridization (ISH) using riboprobes. Basophilic
      granular cytoplasmic inclusions were identified in cytomegalic cells often found
      beneath endothelium, and hexagonal virus particles typical of iridovirus were
      identified in the cytoplasm of enlarged cells by transmission electron
      microscopy. Attempts at virus isolation in cell culture were unsuccessful;
      however, polymerase chain reaction (PCR)-based molecular testing resulted in
      amplification and sequencing of regions of the DNA polymerase and major capsid
      protein genes, along with the full-length ATPase gene of the putative iridovirus.
      Virus gene sequences were then used to infer phylogenetic relationships of the P.
      kauderni agent to other known systemic iridoviruses from fishes. Riboprobes,
      which were transcribed from a cloned PCR amplification product from the viral
      genome generated hybridization signals from inclusions within cytomegalic cells
      in histologic sections tested in ISH experiments. To the authors' knowledge, this
      is the first report of a systemic iridovirus from P. kauderni. The pathologic
      changes induced and the genomic sequence data confirm placement of the Banggai
      cardinalfish iridovirus in the genus Megalocytivirus family Iridoviridae. The ISH
      provides an additional molecular diagnostic technique for confirmation of
      presumptive infections detected in histologic sections from infected fish.

PMID- 19407083
TI  - Performance of real-time reverse transcription polymerase chain reaction for the
      detection of foot-and-mouth disease virus during field outbreaks in the United
      Kingdom in 2007.
AB  - Rapid and accurate diagnosis is essential for effective control of foot-and-mouth
      disease (FMD). The present report describes the practical steps undertaken to
      deploy a real-time reverse transcription polymerase chain reaction (real-time RT
      PCR) to process the samples received during the outbreaks of FMD in the United
      Kingdom in 2007. Two independent real-time RT-PCR assays targeting different
      regions (5'UTR and 3D) of the FMD virus (FMDV) genome were used to confirm the
      presence of FMDV in clinical samples collected from the first infected premises.
      Once the FMDV strain responsible had been sequenced, a single real-time RT-PCR
      assay (3D) was selected to test a total of 3,216 samples, including material from
      all 8 infected premises. Using a 96-well automated system to prepare nucleic acid
      template, up to 84 samples could be processed within 5 hr of submission, and up
      to 269 samples were tested per working day. A conservative cut-off was used to
      designate positive samples, giving rise to an assay specificity of 99.9% or 100%
      for negative control material or samples collected from negative premises,
      respectively. For the first time, real-time RT-PCR results were used to recognize
      preclinical FMD in a cattle herd. Furthermore, during the later stages of the
      outbreaks, the real-time RT-PCR assay supported an active surveillance program
      within high-risk cattle herds. To the authors' knowledge, this is the first
      documented use of real-time RT-PCR as a principal laboratory diagnostic tool
      following introduction of FMD into a country that was FMD-free (without
      vaccination) and highlights the advantages of this assay to support control
      decisions during disease outbreaks.

PMID- 19407080
TI  - A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces
      seizures without impairing hippocampus-dependent learning.
AB  - Previous studies suggest that selective antagonists of specific subtypes of
      muscarinic acetylcholine receptors (mAChRs) may provide a novel approach for the
      treatment of certain central nervous system (CNS) disorders, including epileptic
      disorders, Parkinson's disease, and dystonia. Unfortunately, previously reported
      antagonists are not highly selective for specific mAChR subtypes, making it
      difficult to definitively establish the functional roles and therapeutic
      potential for individual subtypes of this receptor subfamily. The M(1) mAChR is
      of particular interest as a potential target for treatment of CNS disorders. We
      now report the discovery of a novel selective antagonist of M(1) mAChRs, termed
      VU0255035 [N-(3-oxo-3-(4-(pyridine-4-yl)piperazin-1-yl)propyl)
      benzo[c][1,2,5]thiadiazole-4 sulfonamide]. Equilibrium radioligand binding and
      functional studies demonstrate a greater than 75-fold selectivity of VU0255035
      for M(1) mAChRs relative to M(2)-M(5). Molecular pharmacology and mutagenesis
      studies indicate that VU0255035 is a competitive orthosteric antagonist of M(1)
      mAChRs, a surprising finding given the high level of M(1) mAChR selectivity
      relative to other orthosteric antagonists. Whole-cell patch-clamp recordings
      demonstrate that VU0255035 inhibits potentiation of N-methyl-D-aspartate receptor
      currents by the muscarinic agonist carbachol in hippocampal pyramidal cells.
      VU0255035 has excellent brain penetration in vivo and is efficacious in reducing
      pilocarpine-induced seizures in mice. We were surprised to find that doses of
      VU0255035 that reduce pilocarpine-induced seizures do not induce deficits in
      contextual freezing, a measure of hippocampus-dependent learning that is
      disrupted by nonselective mAChR antagonists. Taken together, these data suggest
      that selective antagonists of M(1) mAChRs do not induce the severe cognitive
      deficits seen with nonselective mAChR antagonists and could provide a novel
      approach for the treatment certain of CNS disorders.

PMID- 19407084
TI  - Detection of Border disease virus in fetuses, stillbirths, and newborn lambs from
      natural and experimental infections.
AB  - The purpose of the present study was to evaluate the use of enzyme-linked
      immunosorbent assay (ELISA) antigen detection in blood or fetal fluids and
      reverse transcription polymerase chain reaction (RT-PCR) amplification in tissues
      for routine laboratory diagnosis of Border disease virus (BDV) infection. Samples
      from 67 fetuses, 6 stillbirths, and 11 lambs from 25 commercial flocks with
      suspicion of BDV abortion and 3 fetuses, 7 stillbirths, and 15 lambs obtained
      from an experimental infection with a local isolate (BDV genotype 4) were
      investigated. Presence of BDV was detected by RT-PCR in 7.9% of fetuses, 50% of
      stillbirths, and 50% of lambs from the commercial flocks analyzed, corresponding
      to 8 of the 25 farms (32%). A similar percentage of the lambs and stillbirths
      from the experimental infection were positive by RT-PCR of tissue samples
      (54.5%), and the highest positivity was detected in lymph node, thyroid gland,
      and kidney. The current study revealed that RT-PCR analysis of stillbirths and
      lambs with clinical symptoms is more suitable than the analysis of fetuses to
      confirm the presence of BDV in a flock. Pestiviral antigen was detected by
      antigen ELISA in a high proportion of fetuses (24/58) and stillbirths (3/4) from
      commercial flocks, but in lambs, the presence of colostral antibodies masked the
      detection of the antigen by ELISA. Nevertheless, in lambs from the experimental
      infection that were not fed colostrum, antigen ELISA was less efficient than RT
      PCR in detecting viral presence in stillbirths and lambs. Antigen ELISA is
      therefore recommended for fetuses with advanced autolysis that can adversely
      affect RNA integrity.

PMID- 19407085
TI  - Clinical findings and serum cardiac troponin I concentrations in horses after
      intragastric administration of sodium monensin.
AB  - Six adult horses were administered sodium monensin, 1.0-1.5 mg/kg, via gastric
      gavage. Anorexia and/or diarrhea occurred within 24 hr after monensin
      administration in all 6 horses. Cardiac disease and dysfunction were evaluated by
      both elevations in heart rate, echocardiography, and an increase in serum
      concentrations of cardiac troponin I (cTnI), occurred in 4 horses. The
      development and severity of cardiac disease was likely affected by the monensin
      dose, vehicle (water or corn oil) mixed with monensin, and/or whether the
      monensin was administered to fed or fasted horses. Initial increases in cTnI
      concentrations occurred between 24 and 72 hr after monensin administration. The 2
      horses with the highest cTnI concentrations died or were euthanized within 5 days
      after monensin administration and had severe cardiac disease. One horse had
      increased cTnI concentrations from day 2 to day 16, but no apparent change in
      ventricular contractile function was evident on echocardiography. The fourth
      diseased horse did not return to cTnI reference intervals until day 27 after
      monensin administration, and the ventricular function was still abnormal just
      before euthanasia 9 months later. Cardiac troponin I measurements could be useful
      in managing farm outbreaks of accidental monensin feeding by the early
      identification of horses with cardiac disease.

PMID- 19407086
TI  - Comparison of three rapid commercial Canine parvovirus antigen detection tests
      with electron microscopy and polymerase chain reaction.
AB  - Different antibody-based tests for rapid detection of Canine parvovirus antigens
      in feces are commercially available, allowing quick diagnosis in a clinical
      setting. However, the diagnostic accuracy of these tests compared with standard
      methods has not been evaluated so far. In the current study, 3 commercial tests
      were compared with immune-electron microscopy (IEM) and polymerase chain reaction
      (PCR). Dogs were divided into 3 groups: group A, samples from dogs with acute
      hemorrhagic diarrhea (n = 50); group B, dogs with chronic diarrhea (n = 10); and
      group C, dogs with no evidence of gastrointestinal disease (n = 40). Specificity
      of all 3 commercial tests versus PCR and IEM was good to excellent (92.2-100%).
      Sensitivity, in contrast, was poor: 15.8-26.3% versus PCR and 50-60% versus IEM.
      In group A, 10 dogs were positive by IEM and 24 dogs were positive by PCR.
      Positive PCR results were also obtained from animals in control groups (group B,
      1 dog; group C, 5 dogs). No dog in group B or C was positive by IEM. In
      conclusion, the rapid tests are useful to diagnose canine parvoviral enteritis,
      but they do not rule out parvovirus infection in an animal with typical clinical
      signs. In addition, a small percentage of healthy dogs and dogs with chronic
      diarrhea showed positive PCR results; this may be due to asymptomatic/persistent
      infection or intestinal passage of virus. The significance of this finding
      remains unclear.

PMID- 19407087
TI  - Stability of Bovine viral diarrhea virus antigen in ear punch samples collected
      from bovine fetuses.
AB  - Fourteen first-calf heifers were tested free of antibodies against Bovine viral
      diarrhea viruses (BVDV) by serum neutralization and free of BVDV by polymerase
      chain reaction. Twelve were exposed to BVDV-1b strain CA0401186a at 84-86 days of
      gestation, and 2 were exposed to mock inoculum and served as negative controls.
      Fetuses were harvested by cesarean section at 115-117 days of gestation. The 12
      fetuses removed from the BVDV-exposed heifers were BVDV positive based on virus
      isolation from kidney, thymus, cerebellum, and spleen. It can be assumed that
      these fetuses would have developed into persistently infected calves had they
      been allowed to go to term. Virus was not isolated from the fetuses of control
      animals. Ear punch samples were collected from all fetuses at time of harvest.
      Antigen capture enzyme-linked immunosorbent assay (ACE), using a commercial kit,
      was performed on ear punch samples that were frozen within 5 hr of collection and
      stored at -20 degrees C until tested, tested after storage for 7 days at room
      temperature (18-25 degrees C), or tested after storage for 7 days at 37 degrees
      C. Samples stored for 7 days at room temperature or 37 degrees C lost an average
      of 34% of their starting weight. All samples from BVDV isolation-positive fetuses
      tested positive by ACE, whereas samples from nonexposed fetuses tested negative,
      regardless of storage conditions. These results suggest that ACE testing of skin
      samples collected from aborted fetuses and stillborn calves found in the field
      may represent a practical surveillance method for BVDV-induced reproductive
      disease.

PMID- 19407088
TI  - Reverse transcription loop-mediated isothermal amplification for the detection of
      Porcine reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is an important
      pathogen of swine. The objective of the current study is to investigate the
      feasibility of using reverse transcription loop-mediated isothermal amplification
      (RT-LAMP) for the detection of PRRSV. The RT-LAMP is a recently described DNA
      amplification technique reported to be simple, inexpensive, fast, and accurate.
      The RT-LAMP reaction was set up using 2 sets of primers that were designed to
      detect North American and European strains of PRRSV and performed successfully in
      a simple heat block. The specificity of the amplified product was demonstrated by
      restriction analysis. The RT-LAMP was able to detect 5 different PRRSV isolates.
      However, the limit of detection ranged between 10(2) and 10(4) 50% tissue culture
      infective dose/ml. The RT-LAMP was further evaluated using serum samples from
      animals of known infection status. The ability of RT-LAMP to detect PRRSV in
      serum from acutely infected animals was evaluated with 114 serum samples from 18
      experimentally inoculated boars. Forty-nine of these samples tested positive by
      RT-LAMP, while 94 were positive by reverse transcription polymerase chain
      reaction (RT-PCR). The diagnostic specificity, evaluated with 100 known negative
      serum samples, was estimated as 99%. The feasibility of RT-LAMP to detect PRRSV
      was demonstrated in the current study. The RT-LAMP reaction could be performed in
      just 1 hr with a simple and inexpensive heat block. However, the sensitivity of
      this technique was significantly lower than that of RT-PCR.

PMID- 19407089
TI  - Comparison of three DNA extraction methods for detection of Erysipelothrix
      rhusiopathiae in chicken blood by polymerase chain reaction.
AB  - A previously reported Erysipelothrix-specific polymerase chain reaction (PCR) was
      used to detect Erysipelothrix bacteremia in chickens. The sensitivity of PCR
      using 3 DNA extraction methods (boiling method, commercial gene matrix, and DNA
      extractor kit) was compared by using a serial 10-fold dilution of a chicken
      isolate of Erysipelothrix rhusiopathiae strain in chicken blood. Of the
      techniques used, the DNA extractor kit, followed by PCR, provided the most
      sensitive method for the detection of the E. rhusiopathiae strain in chicken
      blood (approximately 10(0) CFU/0.1 ml of blood). Two E. rhusiopathiae infection
      experiments were then attempted. In a total of 10 inoculated chickens, bacteremia
      developed in 9 chickens, consisting of all 5 chickens used in the first trial
      (ranging from 5.1 x 10(1) to 2.0 x 10(3) CFU/0.1 ml of blood) and 4 of the 5
      chickens used in the second trial (ranging from 1.0 x 10(0) to 3.3 x 10(2)
      CFU/0.1 ml of blood). In the second trial, the 3 detection techniques were
      applied to the chickens with bacteremia, and the organism could be detected by
      using the DNA extractor kit in blood specimens from the 3 chickens exhibiting
      bacteremia of > or =4.2 x 10(1) CFU/0.1 ml of blood. This observation suggests
      that most E. rhusiopathiae-infected chickens develop more critical bacteremia
      than the detectable level by PCR with the DNA extractor kit, and the PCR
      detection method can be used as a first-line screening of avian erysipelas.

PMID- 19407090
TI  - Comparison of genotypes of Escherichia coli strains carrying F18ab and F18ac
      fimbriae from pigs.
AB  - Escherichia coli carrying the F18 fimbriae colonize the small intestine of pigs
      and cause postweaning diarrhea and edema disease. There are 2 closely related
      antigenic variants of F18, F18ab, and F18ac. While F18ab-positive strains are
      known to be associated with edema disease, E. coli-carrying F18ac are known to
      cause diarrhea. One hundred ninety-eight E. coli isolates obtained from cases of
      diarrhea and edema disease in pigs isolated from feces or intestine were screened
      for the presence of the fedA gene encoding for F18 fimbriae. To distinguish
      between F18ab and F18ac, the fedA gene was sequenced in 69 F18-positive
      isolates/strains. The translated protein sequences of the fedA gene in the 2
      variants differ; F18ac protein carries proline at amino acid residue 121, which
      is substituted or missing in F18ab. The F18ab- and F18ac-positive E. coli strains
      were compared for the presence of virulence attributes, serotypes of the
      isolates, and relatedness between the strains. Contrary to earlier reports that
      E. coli F18ab-positive strains mostly express Shiga toxin and F18ac-positive
      strains generally express enterotoxins, the current report shows conclusively for
      the first time that both variant types may carry genes for Shiga toxins and/or
      enterotoxins. Monoclonal antibodies produced against F18ab or F18ac fimbriae
      could not distinguish the strains carrying the 2 variants. Therefore, it was
      concluded that either of the 2 F18 variants, F18ab or F18ac, may be involved in
      causing postweaning diarrhea or edema disease in pigs.

PMID- 19407091
TI  - Validation of the Medonic CA620/530 Vet 20-microl microcapillary sampler system
      for hematology testing of feline blood.
AB  - The aim of the current study was to compare feline hematologic variables in blood
      collected in microcapillary tubes (20 microl) and conventional blood tubes with
      the Medonic CA620/530 Vet in-house hematologic analyzer. A comparison of results
      obtained in 60 cats presented at the clinics of the veterinary school showed that
      the correlations between the 2 methods were 0.97 for white blood cell, 0.95 for
      red blood cell, and 0.93 for platelet counts; 0.92 for hemoglobin concentration;
      and 0.99 for mean corpuscular volume. No clinically relevant differences between
      the 2 blood sampling techniques were observed for any variable, which suggests
      that both techniques are interchangeable in cats. Moreover, microcapillary tubes
      would allow easier repeated sampling in the same cat and would likely be useful
      in other small species.

PMID- 19407092
TI  - Quantitative analysis of telomerase in feline mammary tissues.
AB  - The purpose of this study was to validate immunohistochemistry (IHC) as an
      alternative to telomerase repeat amplification protocol (TRAP) analysis to detect
      telomerase activity. TRAP-enzyme-linked immunosorbent assay (ELISA) reactivity
      was compared with telomerase reverse transcription (TERT) IHC staining in 22
      feline mammary tissues (6 normal mammary glands, 2 dysplastic mammary glands, 1
      fibroadenoma, and 13 malignant neoplasms [6 solid mammary carcinomas, 2 squamous
      cell carcinomas, 4 tubulopapillary mammary carcinomas, and 1 mammary
      carcinosarcoma]). TERT IHC staining revealed enzymatic expression in nuclear,
      nucleolar, cytoplasmic, and combined nuclear and nucleolar staining patterns that
      were separately quantified by image analysis and expressed as the absolute number
      (average) of positive cells or percentage of positive cells with respect to
      overall cellularity. With TERT IHC staining, the absolute number and percentage
      of cells with positive nuclei and nucleoli within the same cell were the
      variables with the greatest discrimination between benign and malignant mammary
      lesions (analysis of variance [ANOVA], average P < 0.0001; percentage P < 0.001).
      For TRAP-ELISA-positive versus TRAP-ELISA-negative tissues, a positive test
      result provided greater differentiation between malignant versus benign mammary
      lesions (ANOVA, average P = 0.00038; percentage P = 0.0022). The same IHC pattern
      of expression showed a proportional and significant (average P = 0.004;
      percentage P = 0.002) but low (average R = 0.60; percentage R = 0.63) correlation
      with TRAP-ELISA by the Pearson test. The correlation coefficients obtained show
      that IHC and TRAP cannot be considered interchangeable because the 2 methods are
      more complementary than exclusive.

PMID- 19407093
TI  - Evidence for Clostridium septicum as a primary cause of cellulitis in commercial
      turkeys.
AB  - Etiology and methods of immunoprophylaxis against common field cellulitis in
      commercial turkeys were evaluated. It was determined that intravenous
      administration ( approximately 10(8) cells/ml) of 1 of 4 isolates of Clostridium
      septicum from cellulitis lesions rapidly caused the classic lesions of cellulitis
      followed by death within 36 hr at high doses. When the supernatant alone was
      injected into turkey poults, signs of depression and ataxia were temporarily
      observed for up to 20 hr after injection, but no cellulitis lesions were
      detected. An enzyme-linked immunosorbent assay was developed to measure antibody
      levels against the isolated C. septicum. This assay was used to predict
      susceptibility to infection. An experimental formalin-killed bacterin/toxoid was
      produced from the challenge strain of C. septicum with inactivation timed to
      allow toxin accumulation and approximately 10(8) cells/ml. This bacterin/toxoid
      given at day of hatch generated a rapid and persistent antibody response against
      the homologous C. septicum in the vaccinated birds at 9 weeks (P < 0.001). The
      ability of this experimental vaccine to protect birds in the field as well as its
      ability to evaluate unvaccinated flocks to establish the time of seroconversion
      and the relationship to clinical disease are currently under evaluation.

PMID- 19407094
TI  - Equine colitis X associated with infection by Clostridium difficile NAP1/027.
AB  - A 14-year-old Quarter Horse with a 48-hr history of colic was euthanized after
      failure to respond to treatment. At necropsy, cecal and colonic mucosae were
      congested throughout, and there was segmental edema and significant thickening of
      the intestinal wall. Excessive numbers of mononuclear cells were found in mucosal
      lamina propria. Submucosal hemorrhage was diffuse and extensive, and Clostridium
      difficile toxins A and B were detected. Large numbers of C. difficile were
      isolated, and genetic characterization revealed them to be North American pulsed
      field gel electrophoresis type 1, polymerase chain reaction ribotype 027, and
      toxinotype III. Genes for the binary toxin were present, and toxin negative
      regulator tcdC contained an 18-bp deletion. This genotype comprises the current
      human "epidemic strain," which is associated with human C. difficile-associated
      disease of greater than historical severity. The diagnosis was peracute
      typhlocolitis, with lesions and history typical of those attributed to colitis X.

PMID- 19407095
TI  - Actinomyces hyovaginalis-associated lymphadenitis in a Nubian goat.
AB  - A 6-year-old Nubian goat with a history of progressive weight loss and cough was
      presented for necropsy. The goat tested negative for antibodies to caseous
      lymphadenitis and caprine arthritis and encephalitis by hemagglutination
      inhibition assay and enzyme-linked immunosorbent assay, respectively. Postmortem
      examination revealed marked enlargement and, with histopathology, a
      fibrinopurulent necrotizing lymphadenitis of a tracheobronchial lymph node, with
      an appearance similar to that reported in cases of caseous lymphadenitis. An
      organism characterized by molecular methods as Actinomyces hyovaginalis was
      isolated together with Staphylococcus spp. and Streptococcus spp. from the
      lesion. No Corynebacterium pseudotuberculosis was recovered. To the authors'
      knowledge, this is the first isolation of A. hyovaginalis from a goat. Although
      the exact contribution of A. hyovaginalis to the lesion remains to be
      established, this case demonstrates that A. hyovaginalis should be considered in
      cases of caseous lymphadenitis-type lesions, especially when C.
      pseudotuberculosis has been excluded.

PMID- 19407097
TI  - An atypical equine gastrointestinal stromal tumor.
AB  - A 17-year-old, gelded Quarter Horse cross was found to have a large, intra
      abdominal mass. Clinical signs included infrequent mild colic, weight loss, and
      chronic anemia. Surgery revealed a very large, discrete, hemorrhagic,
      multilobular mass with vascular attachments to the transverse colon, mesocolon,
      jejunal mesentery, and omentum; the site of origin was the transverse colon.
      Histologic examination demonstrated dense sheets, fascicles, palisades, and
      interconnecting streams of neoplastic spindle cells with lesser numbers of
      admixed multinucleated giant cells. Based on morphology alone, this neoplasm
      might have been misdiagnosed as a peripheral nerve sheath tumor because many of
      the morphologic features were suggestive of neural differentiation. Neoplastic
      cells expressed cluster of differentiation (CD)117 (c-kit), vimentin, desmin,
      smooth muscle actin, neuron-specific enolase, and S-100 protein and did not
      express cytokeratin. Based predominantly on the immunohistochemical profile,
      especially the CD117 positivity, this neoplasm was diagnosed as a
      gastrointestinal stromal tumor with both myogenic and neurogenic differentiation.
      The morphology and immunohistochemical profile of this neoplasm were different
      from published cases of equine gastrointestinal stromal tumors. Unusual aspects
      included the large size of this neoplasm, the neuroid rather than myxomatous
      morphology, the presence of multinucleated giant cells, and the expression of
      desmin.

PMID- 19407096
TI  - Generalized tularemia in a vervet monkey (Chlorocebus aethiops) and a patas
      monkey (Erythrocebus patas) in a zoo.
AB  - Generalized tularemia was diagnosed in a vervet monkey (Chlorocebus aethiops) and
      a patas monkey (Erythrocebus patas), both of which died suddenly in the Szeged
      Zoo, Szeged, Hungary. Macroscopic lesions in each animal included disseminated,
      grayish-white foci in the lungs, lymph nodes, spleen, liver, and kidney. All
      focal lesions were characterized microscopically as purulent to pyogranulomatous
      to granulomatous inflammation with necrosis. Francisella tularensis subsp.
      holarctica strains were isolated from tissue samples on modified Francis agar
      after mouse passage and identified by a commercial carbon-source utilization test
      and polymerase chain reaction-based amplification and sequencing of a portion of
      the 16S ribosomal RNA gene.

PMID- 19407098
TI  - Metastatic angioinvasive lymphoma (lymphomatoid granulomatosis) in a cat.
AB  - A subcutaneous mass removed from the right rear leg of a 17-year-old, spayed,
      female Domestic Shorthair cat was characterized histopathologically by
      granulomatous inflammation, sheets of large atypical lymphoid cells, and
      necrosis. The walls of the small and medium caliber blood vessels were invaded
      transmurally by atypical lymphoid cells. A diagnosis of angioinvasive lymphoma
      (AIL), or lymphomatoid granulomatosis, was made based on histopathologic
      findings. The cat was euthanized 2 months later because of recurrence of the mass
      and elevated serum alanine aminotransferase activity, and a necropsy was
      performed. The histopathologic lesion of AIL was seen in the skin and subcutis of
      the right rear leg, and neoplastic cell infiltrates were seen in adjacent
      skeletal muscle, right superficial inguinal lymph node, liver, and spleen. By
      immunohistochemistry, variable numbers of neoplastic cells expressed B-lymphocyte
      antigen 36 (BLA36) or cluster of differentiation (CD)3 markers, indicative of B-
      and T-cell lineages, respectively. Neoplastic cells were uniformly positive for
      vimentin and uniformly negative for cytokeratins and myeloid/histiocytic antigen.
      Although the cat had received a Rabies virus vaccine subcutaneously in the right
      rear leg 6 months earlier, the AIL lesion was not typical of vaccine-induced
      sarcomas. The AIL in this cat was unusual because the extrapulmonary metastases
      involved the skin and subcutis.

PMID- 19407099
TI  - Copper toxicosis with hemolysis and hemoglobinuric nephrosis in three adult Boer
      goats.
AB  - Acute and, particularly, chronic copper exposures, along with defects in hepatic
      copper metabolism, altered excretion of copper, and/or nutritional imbalances
      between copper and other trace elements, can lead to hepatic accumulation of
      copper and primary copper toxicosis. There is interspecies variation in
      susceptibility to copper toxicosis, with sheep being the species most likely to
      develop this condition. Adult dairy goats and Boer crosses are generally
      considered resistant to chronic copper toxicosis, especially the hemolytic stage
      of this disease. The current report is rather unusual in that it describes
      instances of naturally occurring copper toxicosis with hemolysis and
      hemoglobinuric nephrosis in 3 adult Boer goats. In 2 of these goats, a possible
      source of excessive dietary copper was investigated but not definitively
      identified. In the third goat, the etiologic factors associated with the copper
      toxicosis were not determined. It appears that mature Boer goats are susceptible
      to the hemolytic stage of chronic copper toxicosis, which was not observed in a
      recent, large-scale copper intoxication involving lactating dairy goats. Copper
      analyses on both liver and kidney samples were necessary to confirm the diagnosis
      of copper toxicosis in all 3 goats. All feedstuffs associated with instances of
      copper toxicosis should be analyzed for iron, molybdenum, sulphur, and zinc as
      well as copper to determine what nutritional factors are contributing to the
      pathogenesis of this disease. Consideration also should be given to the ingestion
      of hepatotoxic plants and other toxic exposures, which could predispose an animal
      to secondary chronic copper toxicosis.

PMID- 19407100
TI  - Verminous myelitis in a pit bull puppy.
AB  - A 10-week-old, male pit bull dog presented to the referring veterinarian with
      hind limb paresis and epaxial muscle atrophy. No spinal lesions were identified
      at gross necropsy; however, histologically there was marked granulomatous
      myelitis in the spinal cord between T13 and L2 with occasional, intralesional
      nematode larvae. Based on morphologic characteristics, the nematode larvae were
      identified as Strongyloides spp., possibly Strongyloides stercoralis.

PMID- 19407101
TI  - Fatal onion (Allium cepa) toxicosis in water buffalo (Bubalus bubalis).
AB  - Toxicosis caused by the ingestion of onion (Allium cepa) by 5 water buffalo
      (Bubalus bubalis) occurred in the district of Cacador, Santa Catarina, Brazil.
      The water buffalo died after ingestion of a large quantity of onion that had been
      left in the pasture. Clinical signs started 8 days postingestion and were
      characterized by pale mucous membranes, lethargy, and dark urine. At necropsy,
      pieces of onions were found in the rumen of 1 animal. The carcass smelled
      strongly of onion, and the kidneys and urine were dark brown. Microscopic renal
      lesions included tubular degeneration and necrosis with deposits of eosinophilic
      material in the cytoplasm of renal tubular epithelial cells and tubular lumina.
      These changes were consistent with hemoglobinuric nephrosis. Centrilobular
      coagulation necrosis was observed in the liver accompanied by hemorrhage and
      macrophages containing brown cytoplasmic pigment. A diagnosis of hemolytic anemia
      caused by onion toxicosis was based on the epidemiological data, clinical signs,
      macroscopic changes, and histological lesions.

PMID- 19407103
TI  - Infant parenteral nutrition-associated cholestasis: a severe iatrogenic disease.

PMID- 19407102
TI  - Cyclophosphamide unmasks an antimetastatic effect of local tumor cryoablation.
AB  - Cryoablation of a solitary tumor mass releases intact tumor antigens and can
      induce protective antitumor immunity but has limited efficacy in the treatment of
      established metastatic cancer. Cyclophosphamide (Cy), an anticancer drug,
      selectively depletes regulatory T cells (T(reg)s) and attenuates suppression of
      antitumor immunity. We used a BALB/c mouse model of metastatic colon cancer to
      investigate the systemic antitumor effects of in situ cryotherapy alone or in
      combination with 200 mg/kg i.p. Cy. When combined with Cy, cryoablation was
      significantly more effective than either surgical excision or cautery at inducing
      systemic antitumor immunity, resulting in the cure of a fraction of animals with
      established metastatic disease and resistance to tumor rechallenge. Lymphocytes
      from cured animals contained an expanded population of tumor-specific, interferon
      gamma producing T cells and transferred antitumor immunity to naive recipients.
      Depletion of CD8(+) cells significantly impaired the adoptive transfer of
      antitumor immunity. Furthermore, treatment with Cy and cryoablation was
      associated with a significant decrease in the ratio of regulatory to effector
      CD4(+) T cells. The combination of tumor cryoablation and Cy induces potent,
      systemic antitumor immunity in animals with established metastatic disease.

PMID- 19407104
TI  - Use of nutrition to prevent stress-induced immunosuppression in the pediatric
      intensive care unit: a clinical trials minefield.

PMID- 19407105
TI  - Celebrity endorsement of meta-analysis?

PMID- 19407106
TI  - ABLE: a new and improved amphotericin B for visceral leishmaniasis?

PMID- 19407107
TI  - Nigeria's war on terror: fighting dracunculiasis, onchocerciasis, lymphatic
      filariasis, and schistosomiasis at the grassroots.
AB  - Africa's populous country, Nigeria, contains or contained more cases of
      dracunculiasis, onchocerciasis, lymphatic filariasis, and schistosomiasis than
      any other African nation and ranks or ranked first (dracunculiasis,
      onchocerciasis, schistosomiasis) or third (lymphatic filariasis) in the world for
      the same diseases. After beginning village-based interventions against
      dracunculiasis 20 years ago and confronting onchocerciasis a few years later,
      Nigeria has nearly eliminated dracunculiasis and has provided annual mass drug
      administration for onchocerciasis to over three quarters of that at-risk
      population for 7 years. With assistance from The Carter Center, Nigeria began
      treating lymphatic filariasis and schistosomiasis in two and three states,
      respectively, over the past decade, while conducting pioneering operational
      research as a basis for scaling up interventions against those diseases, for
      which much more remains to be done. This paper describes the status of Nigeria's
      struggles against these four neglected tropical diseases and discusses challenges
      and plans for the future.

PMID- 19407108
TI  - Images in clinical tropical medicine: disseminated cysticercosis.

PMID- 19407109
TI  - Safety and efficacy of high-dose infusions of a preformed amphotericin B fat
      emulsion for treatment of Indian visceral leishmaniasis.
AB  - Amphotericin B deoxycholate is used as a first-line drug for visceral
      leishmaniasis (VL) in India. Its major drawbacks are prolonged hospitalization of
      treated patients and toxicity. An open label phase II study with pre-formed
      amphotericin B lipid emulsion (ABLE) was conducted to evaluate safety and
      efficacy of four regimens of 15 mg/kg each administered in 1-2 doses. Regimen 1
      was 7.5 mg/kg/day on day 1 and day 3, and regimen 4 was a single bolus infusion
      of 15 mg/kg. The safety profile was excellent with mild infusion reactions seen
      in 38% of the patients. Definitive cure was achieved in 100% of the patients
      treated with regimen 4. The overall cure rate was 87% (95% confidence interval =
      75-94%). In this study, ABLE was safe and had excellent efficacy when given as a
      bolus of 15 mg/kg. More studies with larger number of patients and higher doses
      are needed to establish acceptable, safe and efficacious regimen.

PMID- 19407110
TI  - Leishmaniases in Bolivia: comprehensive review and current status.
AB  - The leishmaniases are protozoan, zoonotic diseases transmitted to human and other
      mammal hosts by the bite of phlebotomine sandflies. Bolivia has the highest
      incidence of cutaneous leishmaniasis (CL) in Latin America (LA), with 33 cases
      per 100,000 population reported in 2006. CL is endemic in seven of the country's
      nine administrative departments. Visceral leishmaniasis (VL) is comparatively
      rare and is restricted to one single focus. Most CL cases are caused by
      Leishmania (Viannia) braziliensis (85% cases); VL is caused by L. (L.) infantum.
      Seven sandfly species are incriminated as vectors and Leishmania infections have
      been detected in several non-human mammal hosts. Transmission is associated with
      forest-related activities, but recently, cases of autochthonous, urban
      transmission were reported. Because most cases are caused by L. (V.)
      braziliensis, Bolivia reports the greatest ratio (i.e., up to 20% of all cases)
      of mucosal leishmaniasis to localized CL cases in LA. Per national guidelines,
      both CL and VL cases are microscopically diagnosed and treated with pentavalent
      antimony.

PMID- 19407111
TI  - Accuracy of malaria diagnosis by microscopy, rapid diagnostic test, and PCR
      methods and evidence of antimalarial overprescription in non-severe febrile
      patients in two Tanzanian hospitals.
AB  - The study was aimed to evaluate the malaria over/underdiagnosis and
      over/underprescription of antimalarial drugs. Between February and March 2007
      blood samples were collected from 336 non-severe febrile outpatients attended in
      two peripheral Tanzanian hospitals. Microscopy and a rapid diagnostic test (RDT)
      were done locally and the accuracy evaluated by qualitative polymerase chain
      reaction (PCR) for Plasmodium spp. The testing was performed at National
      Institute for Infectious Diseases Lazzaro Spallanzani (INMI), Rome, Italy. As a
      result of PCR, we identified 26 malaria cases out of 336 (7.7%) patients.
      Microscopy and RDT accuracies were 93.5% and 97.6%, respectively.
      Overprescription and underdiagnosis rates were 29.3% and 30.8%, respectively. On
      field training, clinical management of febrile illness, and malaria microscopy in
      remote settings should be considered.

PMID- 19407112
TI  - Disruption of Nod-like receptors alters inflammatory response to infection but
      does not confer protection in experimental cerebral malaria.
AB  - Research relating to host inflammatory processes during malaria infection has
      focused on Toll-like receptors, membrane-bound receptors implicated in innate
      sensing, and phagocytosis of parasitized erythrocytes by host cells. This is the
      first study to examine the role of Nod proteins, members of the Nod-like receptor
      (NLR) family of cytoplasmic proteins involved in pathogen recognition, in a
      murine model of cerebral malaria (Plasmodium berghei ANKA, PbA). Here, we find
      that nod1nod2(-/-) mice infected with PbA show no difference in survival or
      parasitemia compared with wild-type infected animals. However, cytokine levels,
      notably those associated with NLR activation including interleukin (IL)1-beta,
      KC, and MCP-1, and proteins linked to malaria pathogenesis, such as interferon
      gamma (IFN-gamma), were decreased in the nod-1nod2(-/-) animals. We therefore
      demonstrate for the first time that Nod proteins are activated in response to
      parasites, and they play a role in regulating host inflammatory responses during
      malaria infection.

PMID- 19407113
TI  - Treatment of severe sepsis with artemether-lumefantrine is associated with
      decreased mortality in Ugandan patients without malaria.
AB  - We enrolled 382 patients at two hospitals in Uganda in a prospective
      observational study of severe sepsis. Because artemisinins improve survival in
      murine sepsis models, we performed a post hoc analysis of the association between
      the use of artemether-lumefantrine (A-L) and mortality in patients with or
      without malaria. In patients with negative malaria smears (N = 328 of 379),
      Kaplan-Meier curves revealed decreased combined inpatient and 30-day mortality
      among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus
      48.8%, SE = 3.2; Log rank chi(2) = 3.93, P = 0.048). The decrease in mortality
      associated with A-L was maintained in the most clinically ill patients determined
      by Karnofsky Performance Scores <or= 50 (16.7%, SE = 15.2 versus 58.3%, SE = 3.7;
      Log rank chi(2) 3.94, P = 0.041). Research into the properties of A-L is needed
      to improve treatment of sepsis without compromising malarial susceptibility.

PMID- 19407114
TI  - Analysis of genetic variability of Plasmodium vivax isolates from different
      Brazilian Amazon areas using tandem repeats.
AB  - Few genetic markers have been described to analyze populations of Plasmodium
      vivax. The genetic variability of P. vivax has been analyzed mainly among
      isolates taken from areas ranging from hyper- to holoendemic areas. These studies
      of genetic variability have neglected many areas with different epidemiologic
      profiles. The purpose of this study was to analyze the genetic variability of P.
      vivax isolates from four different Brazilian Amazon areas. We chose to study the
      five most polymorphic tandem repeats (TRs) identified so far. All TRs studied
      were polymorphic in at least one studied population, with a modal allele at
      nearly all loci. Expected heterozygosity ranged from 0.462 to 0.666 and did not
      correlate with the repeat array length. The genetic distances among the
      populations varied from 0.027 to 0.241, and did not correlate with their
      geographic separation. Tandem repeats identified in P. vivax isolates failed to
      allow geographic clustering.

PMID- 19407115
TI  - Novel dhps and pfcrt polymorphisms in Plasmodium falciparum detected by
      heteroduplex tracking assay.
AB  - Several single nucleotide polymorphisms (SNPs) have been linked to antimalarial
      drug resistance in Plasmodium falciparum. However, standard polymerase chain
      reaction (PCR) methods to detect these polymorphisms are unable to detect SNPs in
      variants representing < 20% of the parasites in a mixed infection, nor can they
      detect polymorphisms at nearby loci. Here we use heteroduplex tracking assays
      (HTAs) to analyze dhps540 mutations in 96 samples from Peru and pfcrt76 mutations
      in 70 samples from China. All samples had been previously analyzed by standard
      PCR. We detected drug-resistant minority variants and two novel non-synonymous
      pfcrt mutations in China. In Peru, we found no drug-resistant minority variants
      and a synonymous mutation in dhps. Thus, even in regions of low malaria
      transmission, HTA assays are more informative than PCR with agarose gel
      electrophoresis.

PMID- 19407116
TI  - Malaria drug shortages in Kenya: a major failure to provide access to effective
      treatment.
AB  - A key bench mark of successful therapeutic policy implementation, and thus
      effectiveness, is that the recommended drugs are available at the point of care.
      Two years after artemether-lumefathrine (AL) was introduced for the management of
      uncomplicated malaria in Kenya, we carried out a cross-sectional survey to
      investigate AL availability in government facilities in seven malaria-endemic
      districts. One of four of the surveyed facilities had none of the four AL weight
      specific treatment packs in stock; three of four facilities were out of stock of
      at least one weight-specific AL pack, leading health workers to prescribe a range
      of inappropriate alternatives. The shortage was in large part caused by a delayed
      procurement process. National ministries of health and the international
      community must address the current shortcomings facing antimalarial drug supply
      to the public sector.

PMID- 19407117
TI  - Plasmodium fieldi: observations on the Hackeri and ABI strains in Macaca mulatta
      monkeys and mosquitoes.
AB  - Macaca mulatta monkeys infected with the Hackeri strain of Plasmodium fieldi had
      maximum parasite counts ranging from 1,300 to 301,320/microL. In 43 intact
      animals infected with the ABI strain, the maximum parasite counts ranged from 672
      to 57,189/microL (median = 15,100/microL); in 46 splenectomized monkeys, the
      maximum parasite count ranged from 660 to 350,000/microL (median =
      52,245/microL). Transmission through Anopheles dirus mosquitoes was obtained on
      11 occasions with pre-patent periods of 9-14 days. Relapses occurred between two
      and eight times during a 1-year period. P. fieldi has potential for testing
      prophylactic and radical curative drugs.

PMID- 19407118
TI  - Reduced efficacy of pyrethroid space sprays for dengue control in an area of
      Martinique with pyrethroid resistance.
AB  - In the Caribbean, insecticide resistance is widely developed in Aedes aegypti and
      represents a serious obstacle for dengue vector control. The efficacy of
      pyrethroid and organophosphate ultra-low volume space sprays was investigated in
      Martinique where Ae. aegypti has been shown to be resistant to conventional
      insecticides. In the laboratory, a wild-field caught population showed high
      levels of resistance to deltamethrin, organophosphate (naled), and pyrethrum.
      Simulated-field trials showed that this resistance can strongly reduce the knock
      down effect and mortality of deltamethrin and synergized pyrethrins when applied
      by thermal-fogging. Conversely, the efficacy of naled was high against
      insecticide-resistant mosquitoes. Chemical analyses of nettings exposed to the
      treatments showed a decrease in residues over distance from release for the
      pyrethroids, and naled was not detected. This finding has important implications
      for dengue vector control and emphasizes the need to develop innovative
      strategies to maintain effective control of resistant Ae. aegypti populations.

PMID- 19407119
TI  - Effect of existing practices on reducing Aedes aegypti pre-adults in key breeding
      containers in Ho Chi Minh City, Vietnam.
AB  - This study aimed to evaluate the effects of existing practices of residents in
      reducing pre-adult Aedes aegypti (L.) infestation and to assess the effect of
      dengue-related knowledge on the practices. A house-to-house survey was conducted
      in two areas with different socioeconomic status in Ho Chi Minh City between
      October and November 2007. Some residents in both the areas used covers on the
      productive containers such as the jars and plastic buckets (i.e., 58% and 81% in
      the two study areas), and it was effective in reducing Ae. aegypti infestation:
      odds ratio (OR) of 4.0 and 4.9 (95% confidence interval [CI]: 1.49-10.76 and 1.2
      19.57, respectively) for the containers with inappropriate covers compared with
      those with appropriate covers in the two areas, respectively. Appropriate cover
      use was an effective practice; however, no beneficial role of the knowledge
      related to dengue in promoting the practice was identified.

PMID- 19407120
TI  - Efficacy of Aquatain, a monomolecular surface film, against the malaria vectors
      Anopheles stephensi and An. gambiae s.s. in the laboratory.
AB  - Monomolecular films are used for mosquito control because of their asphyxiating
      effect on larvae and pupae. Compared with other films, Aquatain mosquito
      formulation (AMF) has an improved spreading ability and flexibility on a water
      surface. In the laboratory, AMF showed larvicidal, pupicidal, and oviposition
      deterrent effects against the malaria vectors Anopheles stephensi and An.
      gambiae. At a dose of 1 mL/m(2), the median lethal time to death for late larval
      instars was 3.02 (95% confidence interval [CI] = 2.76-3.25) and 0.98 (95% CI =
      0.75-1.20) days for An. stephensi and An. gambiae, respectively. None of the
      treated larvae pupated. Pupal mortality reached 100% within two hours for both
      species. AMF repelled gravid females from ovipositing in treated oviposition
      cups. Without the choice of an untreated cup, the lowered water surface tension
      caused most females to drown while attempting to oviposit. This physical control
      method has the potential to become a safe, cost-effective, and resistance-proof
      malaria vector control tool.

PMID- 19407121
TI  - Antifilarial activity of 1,3-diarylpropen-1-one: effect on glutathione-S
      transferase, a phase II detoxification enzyme.
AB  - Chalcone derivatives were evaluated for their antifilarial activity on Setaria
      cervi using glutathione-S-transferase (GST) as a drug target. The compounds 1-(4
      benzotriazol-1-yl-phenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (5), and 3-(4
      methoxyphenyl)-1-(4-pyrrolidin-1-yl-phenyl) prop-2-en-1-one (7) showed a
      significant suppression (P < 0.01) in GST activity of adult female parasite
      extract at 3 microM concentration in vitro. However, GST activity was detected
      along with depletion in GSH level. Except Compounds 1 and 2, all exhibited a
      significant effect on the motility and viability of adult parasites. Compounds 3
      (4-chlorophenyl)-1-(4-piperidin-1-yl-phenyl)prop-2-en-1-one (3), 1-(4
      benzotriazol-1-yl-phenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (5), and 3-(4
      methoxyphenyl)-1-(4-pyrrolidin-1-yl-phenyl) prop-2-en-1-one (7) exhibited major
      irreversible effects on viability and resulted in parasite death and also
      inhibited the GST activity by 84-100% in vitro. We report for the first time the
      antifilarial activity of chalcones on GST of adult parasites. This study also
      strengthens our previous findings where GST is reported as a potential drug
      target for antifilarials.

PMID- 19407122
TI  - Assessing transmission of lymphatic filariasis using parasitologic, serologic,
      and entomologic tools after mass drug administration in American Samoa.
AB  - Assessing the interruption of lymphatic filariasis transmission after annual mass
      drug administration (MDA) requires a better understanding of how to interpret
      results obtained with the available diagnostic tools. We conducted parasitologic,
      serologic, and entomologic surveys in three villages in American Samoa after
      sentinel site surveys suggested filarial antigen prevalence was < 1% after five
      annual MDAs with diethylcarbamazine and albendazole. Antigen and antifilarial
      antibody prevalence ranged from 3.7% to 4.6% and from 12.5% to 14.9%,
      respectively, by village. Only one person was microfilaria positive. Although no
      children less than 10 years of age were antigen positive, antifilarial antibody
      prevalence in this age group was 5.1% and antibody-positive children were
      detected in all three villages. Wuchereria bancrofti-infected mosquitoes were
      also detected in all three villages. Thus, monitoring of infections in mosquitoes
      and antifilarial antibody levels in children may serve as indicators of local
      transmission and be useful for making decisions about program endpoints.

PMID- 19407123
TI  - Xenomonitoring of Wuchereria bancrofti and Dirofilaria immitis infections in
      mosquitoes from American Samoa: trapping considerations and a comparison of
      polymerase chain reaction assays with dissection.
AB  - Entomologic monitoring of filarial infections, xenomonitoring, may have
      advantages in certain epidemiologic situations to assess the presence of
      infections in humans. Hemalum staining and dissection and polymerase chain
      reaction (PCR) were compared to determine the filarial infection status of Aedes
      (Stegomyia) mosquitoes in American Samoa. The overall prevalences of Wuchereria
      bancrofti and Dirofilaria immitis infections in Ae. polynesiensis were,
      respectively, 0.16% and 1.06% by dissection and 0.69% and 1.77% by PCR. Human
      filarial worm DNA rates in Aedes aegypti and Aedes upolensis were 1.16% and
      0.38%, respectively. The results suggest that W. bancrofti transmission to humans
      may be continuing at low levels in some villages despite recent completion of 5
      years of mass drug administration. PCR testing of mosquitoes collected using the
      BG-Sentinel traps represents a promising alternative to landing catches for
      assessing the transmission of filariasis in areas where Ae. polynesiensis and
      related species are the primary vectors.

PMID- 19407125
TI  - Management of chronic strongyloidiasis in immigrants and refugees: is serologic
      testing useful?
AB  - We assessed the usefulness of serologic testing in monitoring strongyloidiasis in
      immigrants after treatment with two doses of ivermectin. An observational study
      was conducted in a group of Cambodian immigrants residing in Melbourne who were
      treated for strongyloidiasis and followed-up in a general practice setting. Two
      doses of ivermectin (200 microg/kg) were administered orally. Periodic serologic
      enzyme-linked immunosorbent assay testing was undertaken for up to 30 months
      after treatment. Antibody titers for Strongyloides sp. decreased in 95% (38 of
      40) of the patients, 47.5% (19 of 40) had a decrease in optical density to less
      than 0.5, and 65% (26 of 40) reached levels consistent with a cure during the
      follow-up period. Serologic testing for Strongyloides sp. is a useful tool for
      monitoring a decrease in antibody levels after effective treatment. This testing
      should be carried out 6-12 months after treatment to ensure a sustained downward
      trend suggestive of cure.

PMID- 19407124
TI  - Role of NO synthase in the development of Trypanosoma cruzi-induced
      cardiomyopathy in mice.
AB  - Trypanosoma cruzi infection results in an increase in myocardial NO and intense
      inflammation. NO modulates the T. cruzi-induced myocardial inflammatory reaction.
      NO synthase (NOS)1-, NOS2-, and NOS3-null mice were infected with T. cruzi
      (Brazil strain). Infected NOS1-null mice had increased parasitemia, mortality,
      and left ventricular inner diameter (LVID). Chronically infected NOS1- and NOS2
      null and wild-type mice (WT) exhibited increased right ventricular internal
      diameter (RVID), although the fold increase in the NOS2-null mice was smaller.
      Infected NOS3-null mice exhibited a significant reduction both in LVID and RVID.
      Reverse transcriptase-polymerase chain reaction showed expression of NOS2 and
      NOS3 in hearts of infected NOS1-null and WT mice, whereas infected NOS2-null
      hearts showed little change in expression of other NOS isoforms. Infected NOS3
      null hearts showed an increase only in NOS1 expression. These results may
      indicate different roles for NOS isoforms in T. cruzi-induced cardiomyopathy.

PMID- 19407126
TI  - Close relationship between clinical regression and specific serology in the
      follow-up of patients with alveolar echinococcosis in different clinical stages.
AB  - We compared four enzyme-linked immunosorbent assays (ELISAs) with 172 serum
      samples from 28 patients with alveolar echinococcosis in different clinical
      stages according to the World Health Organization-PNM (P = parasitic mass in the
      liver, N = involvement of neighboring organs, M = metastasis) staging system. The
      sequential antibody responses against Em (2plus), Em10, and Em18 antigens, and a
      crude antigen extract were measured in cohorts with resected and unresected
      lesions. Antibody levels in all assays correlated with the PNM stage before
      treatment, and the highest correlation was shown for the Em18 assay. The PNM
      stage did not influence the antibody kinetics, but changes in antibody levels
      depended on the treatment. In patients after curative surgery, seroreversion in
      the Em (2plus) ELISA indicated successful resection of lesions in more patients
      than any other assay, irrespective of the clinical stage. There were no
      significant differences in the time before assays that use recombinant or
      purified antigens became unreactive. Antibodies directed against crude antigens
      were detectable longer than other antibodies in all patient cohorts and stages.

PMID- 19407127
TI  - Morphologic organization of pulmonary granulomas in mice infected with
      Paracoccidioides brasiliensis.
AB  - A morphologic study of the lungs was carried out in Swiss mice infected with
      yeast isolated from Paracoccidioides brasiliensis (Pb18). The lung was processed
      1, 2, 4, and 8 weeks after inoculation for histologic staining with hematoxylin
      and eosin (H&E), methenamine silver nitrate (Gomori-Grocott), and picrosirius to
      qualitative and quantitative analyses of the granulomas and the presence of
      fungal lesions. The numbers of CFUs/g counted in the lungs were 189.8 +/- 20.64,
      353.6 +/- 46.21, 547.2 +/- 108.1, and 295.2 +/- 89.17 in the first, second,
      fourth, and eighth weeks, respectively. One week after infection, inflammatory
      cells and reticular and collagens fibers, the latest typical of fibrosis, were
      detected. After 2 and 4 weeks, a progressive intensification of the infection and
      fibrosis was observed, but in week 8 a more organized granuloma was evident, with
      macrophages, epithelioid cells, and yeasts in the central portion, and intense
      peripheral basophilia. Pycnotic structures typical of apoptotic bodies were
      observed in weeks 1 and 8. The different histologic staining used acted as a
      fundamental tool for the study of the morphologic organization of granuloma
      formation.

PMID- 19407128
TI  - The profile of health problems in African immigrants attending an infectious
      disease unit in Melbourne, Australia.
AB  - The number of African immigrants living in Western countries is increasing. A
      retrospective audit of sub-Saharan African patients attending the infectious
      diseases clinics of a Melbourne teaching hospital was performed. A total of 375
      patients were included. Helicobacter pylori gastritis was diagnosed in 60% of
      those tested (35/58), schistosomiasis in 41% (84/206), chronic hepatitis B in 19%
      (32/167), and strongyloidiasis in 18% (32/179). Active tuberculosis (TB) affected
      18% (51/276) and latent TB 55% (152/276). Pathologic parasites were detected in
      stool in 21% (31/145). Vitamin D deficiency (< 50 nmol/L) affected 73% (139/191),
      anemia 17% (52/312), iron deficiency 15% (22/151), and low neutrophil count 25%
      (78/312). Infectious diseases, vitamin D deficiency, anemia, and latent TB were
      common in sub-Saharan African immigrants. Clinicians need to be aware of these
      conditions to meet the health needs of this group. Comprehensive health checks
      should be encouraged for new arrivals, particularly from high-risk areas.

PMID- 19407129
TI  - Population-based study of a widespread outbreak of diarrhea associated with
      increased mortality and malnutrition in Botswana, January-March, 2006.
AB  - In early 2006, coinciding with heavy rains, Botswana health facilities reported
      increases in diarrhea, mortality, and acute malnutrition among young children.
      Data on diarrhea, human immunodeficiency virus, feeding, mortality, and
      water/sanitation were collected by random cluster survey. Anthropometric data
      were measured and drinking water samples were tested. Of 537 surveyed children
      less than five years of age, one-third experienced >or= 1 episode of diarrhea.
      Prevalence of acute malnutrition was 7.9%, and the mortality rate for children
      less than five years of age was 2.6/10,000/day during the outbreak. Significant
      risk factors for diarrhea included an age less than two years; breastfeeding was
      protective. Diarrhea lasting for more than 14 days and failure to thrive were
      risk factors for acute malnutrition. Prevalence of acute malnutrition was higher
      than previously documented and the mortality rate in children less than five
      years of age during the outbreak was above the international threshold for
      emergency action with an estimated 547 excess deaths. This survey highlights the
      need for safe infant feeding and effective treatment of malnutrition and diarrhea
      in young children.

PMID- 19407130
TI  - Laboratory assessment of a gravity-fed ultrafiltration water treatment device
      designed for household use in low-income settings.
AB  - Interventions to improve water quality, particularly when deployed at the
      household level, are an effective means of preventing endemic diarrheal disease,
      a leading cause of mortality and morbidity in the developing world. We assessed
      the microbiologic performance of a novel water treatment device designed for
      household use in low-income settings. The device employs a backwashable hollow
      fiber ultrafiltration cartridge and is designed to mechanically remove enteric
      pathogenic bacteria, viruses, and protozoan cysts from drinking water without
      water pressure or electric power. In laboratory testing through 20,000 L
      (approximately 110% of design life) at moderate turbidity (15 nephelometric
      turbidity unit [NTU]), the device achieved log(10) reduction values of 6.9 for
      Escherichia coli, 4.7 for MS2 coliphage (proxy for enteric pathogenic viruses),
      and 3.6 for Cryptosporidium oocysts, thus exceeding levels established for
      microbiological water purifiers. With periodic cleaning and backwashing, the
      device produced treated water at an average rate of 143 mL/min (8.6 L/hour)
      (range 293 to 80 mL/min) over the course of the evaluation. If these results are
      validated in field trials, the deployment of the unit on a wide scale among
      vulnerable populations may make an important contribution to public health
      efforts to control intractable waterborne diseases.

PMID- 19407132
TI  - Microbiologic characterization and antimicrobial susceptibility of Clostridium
      tetani isolated from wounds of patients with clinically diagnosed tetanus.
AB  - Clostridium tetani is the etiologic agent of the muscle-spasming disease tetanus.
      Despite an effective vaccine, tetanus is an ongoing problem in some developing
      countries. Diagnosis by bacterial culture is not done because it is generally
      unnecessary and the entry of route of the bacteria can be inapparent. We
      attempted to isolate and evaluate C. tetani from the wounds of 84 patients with
      tetanus. We effectively isolated C. tetani from 45 patients. All strains tested
      positive by polymerase chain reaction for the gene encoding tetanus neurotoxin.
      Antimicrobial susceptibilities were determined by disc diffusion and E-test. All
      C. tetani isolates were susceptible to penicillin and metronidazole but resistant
      to co-trimoxazole. Despite treatment with high doses of penicillin, C. tetani was
      isolated after 16 days of intravenous penicillin in two cases. These data show
      that the intravenous route for penicillin may be inadequate for clearing the
      infection and emphasizes wound debridement in the treatment of tetanus.

PMID- 19407131
TI  - Attribution of malnutrition to cause-specific diarrheal illness: evidence from a
      prospective study of preschool children in Mirpur, Dhaka, Bangladesh.
AB  - We examined whether malnutrition (underweight [WAZ] < -2) increased the risk of
      diarrhea equally for all enteropathogens. The study was conducted prospectively
      between January 1999 and July 2002 in Mirpur, an urban slum in Dhaka. Two hundred
      eighty-nine Bangladeshi children (147 male and 142 female) 2-5 years of age were
      included in the study. Malnutrition was present in 39% of the children at the
      time of enrollment. The parents and children were visited and interviewed every
      other day by health care workers for details about any diarrheal episodes. Stool
      samples were successfully collected from 62% of episodes of diarrhea. Of the
      identified enteropathogens, only enterotoxigenic Escherichia coli (ETEC),
      Cryptosporidium sp., and Entamoeba histolytica were significantly more prevalent
      in malnourished children. We concluded that the malnutrition attributed risk is
      not equal for enteric pathogens associated with diarrheal illness.

PMID- 19407133
TI  - Pulmonary disease in hamsters infected with Leptospira interrogans:
      histopathologic findings and cytokine mRNA expressions.
AB  - Our aim was to evaluate the pulmonary changes induced by Leptospira interrogans
      infection in hamsters, and the gene expression of endogenous mediators in lung
      fragments during 28 days of observation. The animals were euthanized on days 4,
      7, 14, 21, and 28 post-inoculation. Histopathologic lung analysis showed
      hemorrhage, pneumonia, alveolar congestion, and infiltrated cellular areas, with
      increasing severity until day 21 post-inoculation. Tumor necrosis factor (TNF)
      alpha mRNA expression enhanced in first days with peak on day 4 and slightly
      decreased in the final phase. The interleukin (IL)-10 remained relatively
      constant throughout the period, with the exceptions of days 4 and 14. The
      endothelial nitric-oxide synthesis (eNOS) showed an increased expression on day
      4, followed by an augment on days 7 and 14, and remaining constant up to day 28
      post-infection. Our results demonstrate that inoculation of L. interrogans
      sorovar Icterohaemorrhagiae induced pulmonary lesions, including pulmonary
      hemorrhage, supporting that the lung is a target organ.

PMID- 19407134
TI  - Comparison of indirect immunofluorescence assays for diagnosis of scrub typhus
      and murine typhus using venous blood and finger prick filter paper blood spots.
AB  - We performed indirect immunofluorescence assays (IFAs) to compare levels of IgM
      and IgG antibodies to Orientia tsutsugamushi and Rickettsia typhi in admission
      phase serum samples and filter paper blood spots (assayed immediately and stored
      at 5.4 degrees C and 29 degrees C for 30 days) collected on the same day from 53
      adults with suspected scrub typhus and murine typhus admitted to Mahosot Hospital
      Vientiane, Lao People's Democratic Republic. The sensitivities and specificities
      of admission-phase filter paper blood spots in comparison to paired sera were
      between 91% and 95% and 87% and 100%, respectively, for the diagnosis of scrub
      typhus and murine typhus. The classification of patients as having or not having
      typhus did not significantly differ after storage of the blood spots for 30 days
      (P > 0.4) at 5.4 degrees C and 29 degrees C. Because filter paper blood samples
      do not require sophisticated and expensive storage and transport, they may be an
      appropriate specimen collection technique for the diagnosis of rickettsial
      disease in the rural tropics.

PMID- 19407135
TI  - Increased phagocytosis of platelets from patients with secondary dengue virus
      infection by human macrophages.
AB  - The relationship between the percent phagocytosis of platelets by differentiated
      THP-1 cells was examined using flowcytometry and the peripheral platelet counts
      as well as platelet-associated IgG (PAIgG) in 36 patients with secondary dengue
      virus (DV) infections. The percent phagocytosis and the levels of PAIgG were
      significantly increased in these patients during the acute phase compared with
      the healthy volunteers. The increased percent phagocytosis and PAIgG found during
      the acute phase significantly decreased during the convalescent phase. An inverse
      correlation between platelet count and the percent phagocytosis (P = 0.011) and
      the levels of PAIgG (P = 0.041) was found among these patients during the acute
      phase. No correlation was found, however, between the percent phagocytosis and
      the levels of PAIgG. Our present data suggest that accelerated platelet
      phagocytosis occurs during the acute phase of secondary DV infections, and it is
      one of the mechanisms of thrombocytopenia in this disease.

PMID- 19407136
TI  - Cost of dengue cases in eight countries in the Americas and Asia: a prospective
      study.
AB  - Despite the growing worldwide burden of dengue fever, the global economic impact
      of dengue illness is poorly documented. Using a common protocol, we present the
      first multicountry estimates of the direct and indirect costs of dengue cases in
      eight American and Asian countries. We conducted prospective studies of the cost
      of dengue in five countries in the Americas (Brazil, El Salvador, Guatemala,
      Panama, and Venezuela) and three countries in Asia (Cambodia, Malaysia, and
      Thailand). All studies followed the same core protocol with interviews and
      medical record reviews. The study populations were patients treated in ambulatory
      and hospital settings with a clinical diagnosis of dengue. Most studies were
      performed in 2005. Costs are in 2005 international dollars (I$). We studied 1,695
      patients (48% pediatric and 52% adult); none died. The average illness lasted
      11.9 days for ambulatory patients and 11.0 days for hospitalized patients. Among
      hospitalized patients, students lost 5.6 days of school, whereas those working
      lost 9.9 work days per average dengue episode. Overall mean costs were I$514 and
      I$1,394 for an ambulatory and hospitalized case, respectively. With an annual
      average of 574,000 cases reported, the aggregate annual economic cost of dengue
      for the eight study countries is at least I$587 million. Preliminary adjustment
      for under-reporting could raise this total to $1.8 billion, and incorporating
      costs of dengue surveillance and vector control would raise the amount further.
      Dengue imposes substantial costs on both the health sector and the overall
      economy.

PMID- 19407137
TI  - Prevalence of antibodies to Japanese encephalitis virus among inhabitants in Java
      Island, Indonesia, with a small pig population.
AB  - Japanese encephalitis virus (JEV) is maintained through a transmission cycle
      between amplifier swine and vector mosquitoes in a peridomestic environment.
      Thus, studies on natural JEV activities in an environment with a small size of
      pig population have been limited. Here, we surveyed antibodies against JEV in
      inhabitants of Jakarta and Surabaya located in Java Island (Indonesia), which has
      a small swine population. Overall, 2.2% of 1,211 sera collected in Jakarta and
      1.8% of 1,751 sera collected in Surabaya had neutralizing antibody titers of >or=
      1:160 (90% plaque reduction). All the samples with titers of >or= 1:160 against
      JEV were also examined for neutralizing antibodies against each of four dengue
      viruses to confirm that JEV antibody prevalences obtained in the present survey
      were not attributable to serologic cross-reactivities among flaviviruses
      distributed in Java. These results indicated that people in Java Island are
      exposed to natural JEV infections despite a small swine population.

PMID- 19407138
TI  - Comparative thermostability of West Nile, St. Louis encephalitis, and western
      equine encephalomyelitis viruses during heat inactivation for serologic
      diagnostics.
AB  - During the monitoring of arbovirus seroprevalence in wild birds collected in
      California, we inadvertently made two isolates of western equine
      encephalomyelitis virus (WEEV) from California quail sera being tested by plaque
      reduction neutralization assay for antibodies against St Louis encephalitis
      (SLEV) and West Nile (WNV) viruses despite heating the sera at 56 degrees C for
      30 minutes. These data prompted us to examine the thermostability of these
      viruses during heat treatment. The flaviviruses, SLEV and WNV, at titers up to
      10(6) plaque-forming units (PFU), were readily inactivated by the standard
      protocol of heating at 56 degrees C for 30 minutes. In contrast, solutions
      containing 10(5) and 10(6) PFU of WEEV required 2 hours for complete
      inactivation. Occasional presence of live virus within sera could lead to false
      negatives using standard plaque reduction neutralization test protocols.

PMID- 19407140
TI  - Impact of maternal human immunodeficiency virus infection on birth outcomes and
      infant survival in rural Mozambique.
AB  - We assessed the effect of maternal human immunodeficiency virus (HIV) infection
      on birth outcomes and infant survival in rural Mozambique. Pregnant women
      attending the antenatal clinic were recruited. These women and their infants were
      followed-up for one year. Birth outcomes were assessed at delivery and infant HIV
      status was determined at 1 and 12 months of age. Women positive for HIV were more
      likely to have anemia at delivery than women negative for HIV (51.3% versus
      35.4%; P < 0.001). Infants born to HIV-positive mothers had a significantly
      higher post-neonatal mortality rate than infants born to HIV-negative mothers
      (7.8% versus 1.9%; P < 0.001). The rate of transmission of HIV by breastfeeding
      during the first year of life was 15.1% (95% confidence interval = CI 7.6-22.4).
      Assessment of the impact of HIV infection on birth outcomes in rural Africa is
      essential for tailoring public health measures to reduce mother-to-child
      transmission of HIV and excess infant mortality.

PMID- 19407139
TI  - Humoral immunity to West Nile virus is long-lasting and protective in the house
      sparrow (Passer domesticus).
AB  - The house sparrow (Passer domesticus) is a common and abundant amplifying host of
      West Nile virus (WNV) and many survive infection and develop humoral immunity. We
      experimentally inoculated house sparrows with WNV and monitored duration and
      protection of resulting antibodies. Neutralizing antibody titers remained
      relatively constant for >or= 36 months (N = 42) and provided sterilizing immunity
      for up to 36 months post-inoculation in 98.6% of individuals (N = 72). These
      results imply that immune house sparrows are protected from WNV infection for
      multiple transmission seasons. Additionally, individuals experiencing WNV
      associated mortality reached significantly higher peak viremia titers than
      survivors, and mortality during acute infection was significantly higher in caged
      versus free-flight sparrows. A better understanding of the long-term immunity and
      mortality rates in birds is valuable in interpreting serosurveillance and
      diagnostic data and modeling transmission and disease dynamics.

PMID- 19407141
TI  - A reduced abbreviated indirect calorimetry protocol is clinically acceptable for
      use in spontaneously breathing patients with traumatic brain injury.
AB  - A steady state should be established when using indirect calorimetry to assess
      resting energy expenditure, reduce error, and improve the validity of the
      measurement. Steady-state criteria are often rigorous and difficult to achieve in
      hospitalized patients, particularly in patients recovering from traumatic brain
      injury. This study aimed to assess whether reducing the timeframe for steady
      state conditions to 2, 3, or 4 minutes when using indirect calorimetry was
      significantly different from the widely accepted 5-minute steady-state protocol
      in patients recovering from traumatic brain injury. Indirect calorimetry using an
      open-circuit calorimeter was used to measure resting energy expenditure in 20
      spontaneously breathing patients with traumatic brain injury. Each patient
      underwent repeated measurements once per day at various stages of his or her
      recovery. Bland-Altman methods comparison was used for statistical analysis. In
      total, 124 measurements were recorded, of which 59% met 5-minute, 70% met 4
      minute, 76% met 3-minute, and 84% met 2-minute steady-state conditions. Mean
      within-patient coefficient of variation was 13% (range, 0%-35%). Agreement at the
      +/-10% level using Bland-Altman plots was 100% for a 4-minute steady-state
      protocol, 96% for a 3-minute protocol, and 90% using a 2-minute protocol. A 4
      minute or 3-minute abbreviated steady-state indirect calorimetry protocol is
      clinically acceptable to measure resting energy expenditure in spontaneously
      breathing patients with a traumatic brain injury.

PMID- 19407142
TI  - Abscisic acid inhibits type 2C protein phosphatases via the PYR/PYL family of
      START proteins.
AB  - Type 2C protein phosphatases (PP2Cs) are vitally involved in abscisic acid (ABA)
      signaling. Here, we show that a synthetic growth inhibitor called pyrabactin
      functions as a selective ABA agonist. Pyrabactin acts through PYRABACTIN
      RESISTANCE 1 (PYR1), the founding member of a family of START proteins called
      PYR/PYLs, which are necessary for both pyrabactin and ABA signaling in vivo. We
      show that ABA binds to PYR1, which in turn binds to and inhibits PP2Cs. We
      conclude that PYR/PYLs are ABA receptors functioning at the apex of a negative
      regulatory pathway that controls ABA signaling by inhibiting PP2Cs. Our results
      illustrate the power of the chemical genetic approach for sidestepping genetic
      redundancy.

PMID- 19407143
TI  - Regulators of PP2C phosphatase activity function as abscisic acid sensors.
AB  - The plant hormone abscisic acid (ABA) acts as a developmental signal and as an
      integrator of environmental cues such as drought and cold. Key players in ABA
      signal transduction include the type 2C protein phosphatases (PP2Cs) ABI1 and
      ABI2, which act by negatively regulating ABA responses. In this study, we
      identify interactors of ABI1 and ABI2 which we have named regulatory components
      of ABA receptor (RCARs). In Arabidopsis, RCARs belong to a family with 14 members
      that share structural similarity with class 10 pathogen-related proteins. RCAR1
      was shown to bind ABA, to mediate ABA-dependent inactivation of ABI1 or ABI2 in
      vitro, and to antagonize PP2C action in planta. Other RCARs also mediated ABA
      dependent regulation of ABI1 and ABI2, consistent with a combinatorial assembly
      of receptor complexes.

PMID- 19407145
TI  - Dispersion of the excitations of fractional quantum Hall States.
AB  - The rich correlation physics in two-dimensional (2D) electron systems is governed
      by the dispersion of its excitations. In the fractional quantum Hall regime,
      excitations involve fractionally charged quasi particles, which exhibit
      dispersion minima at large momenta referred to as rotons. These rotons are
      difficult to access with conventional techniques because of the lack of
      penetration depth or sample volume. Our method overcomes the limitations of
      conventional methods and traces the dispersion of excitations across momentum
      space for buried systems involving small material volume. We used surface
      acoustic waves, launched across the 2D system, to allow incident radiation to
      trigger these excitations at large momenta. Optics probed their resonant
      absorption. Our technique unveils the full dispersion of such excitations of
      several prominent correlated ground states of the 2D electron system, which has
      so far been inaccessible for experimentation.

PMID- 19407146
TI  - Superconductivity at the two-dimensional limit.
AB  - Superconductivity in the extreme two-dimensional limit is studied on ultrathin
      lead films down to two atomic layers, where only a single channel of quantum well
      states exists. Scanning tunneling spectroscopy reveals that local superconducting
      order remains robust until two atomic layers, where the transition temperature
      abruptly plunges to a lower value, depending sensitively on the exact atomic
      structure of the film. Our result shows that Cooper pairs can still form in the
      last two-dimensional channel of electron states, although their binding is
      strongly affected by the substrate.

PMID- 19407144
TI  - The genetic structure and history of Africans and African Americans.
AB  - Africa is the source of all modern humans, but characterization of genetic
      variation and of relationships among populations across the continent has been
      enigmatic. We studied 121 African populations, four African American populations,
      and 60 non-African populations for patterns of variation at 1327 nuclear
      microsatellite and insertion/deletion markers. We identified 14 ancestral
      population clusters in Africa that correlate with self-described ethnicity and
      shared cultural and/or linguistic properties. We observed high levels of mixed
      ancestry in most populations, reflecting historical migration events across the
      continent. Our data also provide evidence for shared ancestry among
      geographically diverse hunter-gatherer populations (Khoesan speakers and
      Pygmies). The ancestry of African Americans is predominantly from Niger
      Kordofanian (approximately 71%), European (approximately 13%), and other African
      (approximately 8%) populations, although admixture levels varied considerably
      among individuals. This study helps tease apart the complex evolutionary history
      of Africans and African Americans, aiding both anthropological and genetic
      epidemiologic studies.

PMID- 19407147
TI  - Benefits in cost and reduced discomfort of new techniques of minimally invasive
      cavity treatment.

PMID- 19407148
TI  - Human papillomavirus and head and neck squamous cell carcinoma: recent evidence
      and clinical implications.
AB  - Over the past 20 years, high-risk human papilloma-virus (HPV) infection has been
      established as a risk factor for developing head and neck squamous cell
      carcinoma, independent of tobacco and alcohol use. In particular, HPV is strongly
      associated with the development of oropharyngeal cancer and a small minority of
      oral cavity cancers. In this review, we summarize what is currently known about
      the biology of HPV, the mechanisms by which it effects malignant transformation,
      and the potential impact of HPV status on the clinical management of persons with
      head and neck cancer.

PMID- 19407150
TI  - Synergistic roles of amelogenin and ameloblastin.
AB  - Amelogenin and ameloblastin, the major enamel matrix proteins, are important for
      enamel mineralization. To identify their synergistic roles in enamel development,
      we generated Amel X(-/-)/Ambn(-/-) mice. These mice showed additional enamel
      defects in comparison with Amel X(-/-) or Ambn(-/-) mice. In 7-day-old Amel X(-/
      )/Ambn(-/-) mice, not only was the ameloblast layer irregular and detached from
      the enamel surface, as in Ambn(-/-), but also, the enamel width was significantly
      reduced in the double-null mice as compared with Amel X(-/-) or Ambn(-/-) mice.
      Proteomic analysis of the double-null teeth revealed increased levels of RhoGDI
      (Arhgdia), a Rho-family-specific guanine nucleotide dissociation inhibitor, which
      is involved in important cellular processes, such as cell attachment. Both Amel
      X(-/-)/Ambn(-/-) mice and Ambn(-/-) mice displayed positive staining with RhoGDI
      antibody in the irregularly shaped ameloblasts detached from the matrix.
      Ameloblastin-regulated expression of RhoGDI suggests that Rho-mediated signaling
      pathway might play a role in enamel formation.

PMID- 19407151
TI  - DPPI may activate KLK4 during enamel formation.
AB  - Kallikrein-4 (KLK4) is a serine protease expressed during enamel maturation, and
      proteolytic processing of the enamel matrix by KLK4 is critical for proper enamel
      formation. KLK4 is secreted as an inactive zymogen (pro-KLK4), and identification
      of its activator remains elusive. Dipeptidyl peptidase I (DPPI) is a cysteine
      aminopeptidase that can activate several serine proteases. In this study, we
      sought to examine DPPI expression in mouse enamel organ and determine if DPPI
      could activate KLK4. Real-time PCR showed DPPI expression throughout
      amelogenesis, with highest expression at maturation, and immunohistochemical
      staining of mouse incisors confirmed DPPI expression by ameloblasts. We
      demonstrate in vitro that DPPI activates pro-KLK4 to cleave a fluorogenic peptide
      containing a KLK4 cleavage site. Examination of mature enamel from DPPI null mice
      by FTIR showed no significant accumulation of protein; however, microhardness
      testing revealed that loss of DPPI expression significantly reduced enamel
      hardness.

PMID- 19407152
TI  - Adult rat odontoblasts lack noxious thermal sensitivity.
AB  - Dentin hypersensitivity is a common symptom treated in the dental clinic, yet the
      underlying cellular and molecular mechanisms are not clear. We hypothesized that
      odontoblasts detect noxious thermal stimuli by expressing temperature-sensing
      molecules, and investigated whether temperature-activated TRP channels (thermo
      TRP channels), which are known to initiate temperature signaling, mediate
      temperature sensing in odontoblasts. mRNA expression of dentin
      sialophosphoprotein and collagenase type 1, odontoblast-specific proteins, was
      shown in acutely isolated adult rat odontoblasts by single-cell RT-PCR, while
      TRPV1, TRPV2, TRPM8, and TRPA1 were not detected. Application of noxious
      temperatures of 42 degrees C and 12 degrees C, as well as capsaicin, menthol, and
      icilin, agonists of thermo-TRP channels, failed to increase intracellular calcium
      concentration. Immunohistochemical study also revealed no expression of TRPV1.
      Thus, it is unlikely that odontoblasts serve as thermal sensors in teeth via
      thermo-TRP channels.

PMID- 19407149
TI  - Replication and assembly of human papillomaviruses.
AB  - Human papillomaviruses (HPVs) are small dsDNA tumor viruses, which are the
      etiologic agents of most cervical cancers and are associated with a growing
      percentage of oropharyngeal cancers. The HPV capsid is non-enveloped, having a
      T=7 icosahedral symmetry formed via the interaction among 72 pentamers of the
      major capsid protein, L1. The minor capsid protein L2 associates with L1
      pentamers, although it is not known if each L1 pentamer contains a single L2
      protein. The HPV life cycle strictly adheres to the host cell differentiation
      program, and as such, native HPV virions are only produced in vivo or in
      organotypic "raft" culture. Research producing synthetic papillomavirus particles
      -such as virus-like particles (VLPs), papillomavirus-based gene transfer vectors,
      known as pseudovirions (PsV), and papillomavirus genome-containing quasivirions
      (QV)--has bypassed the need for stratifying and differentiating host tissue in
      viral assembly and has allowed for the rapid analysis of HPV infectivity
      pathways, transmission, immunogenicity, and viral structure.

PMID- 19407153
TI  - TGF-beta1 Inhibits TLR-mediated odontoblast responses to oral bacteria.
AB  - TGF-beta1 exerts diverse functions in tooth development and tissue repair, but
      its role in microbial defenses of the tooth is not well-understood. Odontoblasts
      extending their cellular processes into the dentin are the first cells to
      recognize signals from TGF-beta1 and bacteria in carious dentin. This study aimed
      to determine the role of TGF-beta1 in modulating odontoblast responses to oral
      bacteria. We show that these responses depend upon the expression levels of
      microbial recognition receptors TLR2 and TLR4 on the cell surface. Porphyromonas
      gingivalis, Prevotella intermedia, and Fusobacterium nucleatum activated both
      TLRs, but TLR4 played a greater role. Lack of cell-surface TLR2 was associated
      with poor response to Streptococcus mutans, Enterococcus faecalis, and
      Lactobacillus casei. TGF-beta1 inhibited TLR2 and TLR4 expression and attenuated
      odontoblast responses. Our findings suggest that the balance between TLR-mediated
      inflammation and TGF-beta1 anti-inflammatory activity plays an important role in
      pulpal inflammation.

PMID- 19407155
TI  - CTGF and apoptosis in mouse osteocytes induced by tooth movement.
AB  - It is known that experimental tooth movement stimulates the gene expression of
      connective tissue growth factor (CTGF) and induces apoptosis in osteocytes in
      rats. We hypothesized that there is a relationship between CTGF expression and
      the induction of apoptosis in osteocytes, to play a significant role in
      triggering bone remodeling during experimental tooth movement. In this study,
      CTGF mRNA expression was detected at 2 hours in osteocytes on the pressure side,
      followed by apoptosis at 6 hours after tooth movement in mice. The number of
      empty lacunae significantly increased on day 1 after mechanical stimulation.
      Thereafter, the number of osteoclasts significantly increased on the pressure
      side of the alveolar bone on day 3. Tooth movement increased rapidly on day 10.
      These findings suggest that CTGF expression, followed by apoptosis in osteocytes
      in response to mechanical stimulation, might play a significant role in
      triggering bone remodeling during tooth movement.

PMID- 19407154
TI  - TNF-alpha promotes an odontoblastic phenotype in dental pulp cells.
AB  - Dental pulp cells can differentiate toward an odontoblastic phenotype to produce
      reparative dentin beneath caries lesions. However, the mechanisms involved in
      pulp cell differentiation under pro-inflammatory stimuli have not been well
      explored. Thus, we hypothesized that the pro-inflammatory cytokine tumor necrosis
      factor-alpha (TNF-alpha) could be a mediator involved in dental pulp cell
      differentiation toward an odontoblastic phenotype. We observed that TNF-alpha
      challenged pulp cells exhibited increased mineralization and early and increased
      expression of dentin phosphoprotein (DPP), dentin sialoprotein (DSP), dentin
      matrix protein-1, and osteocalcin during a phase of reduced matrix
      metalloproteinase (MMP) expression. We investigated whether these events were
      related and found that p38, a mitogen-activated protein kinase, differentially
      regulated MMP-1 and DSP/DPP expression and mediated mineralization upon TNF-alpha
      treatment. These findings indicate that TNF-alpha stimulates differentiation of
      dental pulp cells toward an odontoblastic phenotype via p38, while negatively
      regulating MMP-1 expression.

PMID- 19407156
TI  - The role of cognitive ability in socio-economic inequalities in oral health.
AB  - Studies have postulated a role for cognitive ability in socio-economic
      inequalities in general health. This role has not been examined for oral health
      inequalities. We examined whether cognitive ability was associated with oral
      health, and whether it influenced the relationship between oral health and socio
      economic position. Data were from the Third National Health and Nutrition
      Examination Survey (1988-1994), for participants aged 20-59 years. Oral health
      was indicated by extent of gingival bleeding, extent of loss of periodontal
      attachment, and tooth loss. Simple reaction time test, symbol digit substitution
      test, and serial digit learning test indicated cognitive ability. Education and
      poverty-income ratio were used as markers of socio-economic position.
      Participants with poorer cognitive ability had poorer oral health for all
      indicators. The association between oral health and socio-economic position
      attenuated after adjustment for cognitive ability. Cognitive ability explained
      part, but not all, of the socio-economic inequalities in oral health.

PMID- 19407157
TI  - Phenotypic variation in FAM83H-associated amelogenesis imperfecta.
AB  - FAM83H gene mutations are associated with autosomal-dominant hypocalcified
      amelogenesis imperfecta (ADHCAI), which is typically characterized by enamel
      having normal thickness and a markedly decreased mineral content. This study
      tested the hypothesis that there are phenotype and genotype associations in
      families with FAM83H-associated ADHCAI. Seven families segregating ADHCAI (147
      individuals) were evaluated. Phenotyping included clinical, radiographic,
      histological, and biochemical studies, and genotyping was by mutational analysis.
      Multiple novel FAM83H mutations were identified, including two 2-bp-deletion
      mutations, the first non-nonsense mutations identified. Craniofacial deviation
      from normal was more prevalent in the affected individuals. Affected individuals
      having truncating FAMH3H mutations of 677 or fewer amino acids presented a
      generalized ADHCAI phenotype, while those having mutations capable of producing a
      protein of at least 694 amino acids had a unique and previously unreported
      phenotype affecting primarily the cervical enamel. This investigation shows that
      unique phenotypes are associated with specific FAM83H mutations.

PMID- 19407158
TI  - Healthy eating index is a predictor of early childhood caries.
AB  - Early childhood caries (ECC) is a preventable form of dental caries that affects
      very young children, particularly among low-income families and certain
      racial/ethnic minorities. The current study examined the relationship of dietary
      quality, as measured by the Healthy Eating Index (HEI), to the prevalence of ECC
      in 2- to 5-year-old children. Data from the Third National Health and Nutrition
      Examination Survey (NHANES III) were used for the study. We used logistic
      regression to compute adjusted odds ratios (OR) for ECC and 95% confidence
      intervals (CI). Children with the best dietary practices (uppermost tertile of
      the HEI) were 44% less likely to exhibit severe ECC compared with children with
      the worst dietary practices (lowest tertile of the HEI). A healthy eating pattern
      geared for promotion of optimal child development and prevention of chronic
      disease in later life may also reduce the risk of early childhood caries,
      particularly severe early childhood caries.

PMID- 19407160
TI  - Anti-biofilm effect of dental adhesive with cationic monomer.
AB  - The incorporation of polymerizable cationic monomers has been attempted to
      generate dental resinous materials with antibacterial activity. This study tested
      the hypothesis that a dental adhesive containing a cationic monomer,
      methacryloxylethyl cetyl dimethyl ammonium chloride (DMAE-CB), would influence
      biofilm formation and gtf gene expression of Streptococcus mutans. The effect of
      the photo-polymerized DMAE-CB-incorporated adhesive on in vitro biofilm
      accumulation was investigated with spectrophotometry and scanning electron
      microscopy. The relative level of gtf gene expression by Streptococcus mutans in
      the biofilm was quantified by real-time reverse-transcription polymerase chain
      reaction. The DMAE-CB-incorporated adhesive significantly decreased bio-film
      accumulation on its surface (P < 0.05), and suppressed the expression of gtfB and
      gtfC of Streptococcus mutans in the biofilm (P < 0.05). The results suggest that
      the cured DMAE-CB-incorporated adhesive may hamper biofilm accumulation via
      selective down-regulation of the expression of gtf genes in Streptococcus mutans.

PMID- 19407159
TI  - Glycemic control and implant stabilization in type 2 diabetes mellitus.
AB  - Diabetes mellitus is considered a relative contra-indication for implant therapy.
      However, the effect of glycemic level on implant integration in persons with
      diabetes remains poorly understood. The hypothesis of this research was that poor
      glycemic control is directly related to short-term-impairment implant
      stabilization. This prospective clinical study evaluated 10 non-diabetic
      individuals (12 implants) and 20 persons with type 2 diabetes (30 implants).
      Glycated hemoglobin (HbA1c) levels ranged from 4.7-12.6%. Implant stability was
      assessed by resonance frequency analysis over 4 months following placement.
      Minimum stability levels were observed 2-6 weeks following placement for all 42
      implants. Persons with HbA1c > or = 8.1% had a greater maximum decrease in
      stability from baseline and required a longer time for healing, as indicated by
      return of stability level to baseline. This study demonstrates alterations in
      implant stability consistent with impaired implant integration for persons with
      type 2 diabetes mellitus in direct relation to hyperglycemic conditions.

PMID- 19407161
TI  - Polypeptide-catalyzed biosilicification of dentin surfaces.
AB  - In situ formation of mineral particles by biocatalysis would be advantageous for
      occluding dentin tubules to reduce permeability or for sealing of material-tooth
      interfaces. One approach would require that the peptide-catalyst remain
      functional on the dentin surface. Based on recent observations of retained
      activity on other surfaces, we hypothesized that poly(L-lysine) (PLL), an analog
      of the protein catalyst responsible for silica formation in primitive marine
      species, would remain functional on dentin. PLL was applied to dentin discs along
      with a pre-hydrolyzed silica precursor, tetramethyl orthosilicate (TMOS). Discs
      were analyzed microscopically (scanning electron microscopy, SEM) and chemically
      (x-ray photoelectron spectroscopy, XPS). The treated discs, but not the negative
      controls, exhibited partial distinct coating whose XPS survey was consistent with
      that of silica, demonstrating that the polypeptide was required and retained its
      mediating activity. Peptide-catalysts that mediate mineral formation can retain
      functionality on dentin, suggesting a wide range of preventive and treatment
      strategies.

PMID- 19407162
TI  - Laboratory simulation of Y-TZP all-ceramic crown clinical failures.
AB  - Clinically, zirconia-supported all-ceramic restorations are failing by veneer
      chipping without exposing the zirconia interface. We hypothesized that mouth
      motion step-stress-accelerated fatigue testing of standardized dental crowns
      would permit this previously unrecognized failure mode to be investigated. Using
      CAD software, we imported the average dimensions of a mandibular first molar
      crown and modeled tooth preparation. The CAD-based tooth preparation was rapid
      prototyped as a die for fabrication of zirconia core porcelain-veneered crowns.
      Crowns were bonded to aged composite reproductions of the preparation and aged 14
      days in water. Crowns were single-cycle-loaded to failure or mouth-motion step
      stress- fatigue-tested. Finite element analysis indicated high stress levels
      below the load and at margins, in agreement with only single-cycle fracture
      origins. As hypothesized, the mouth motion sliding contact fatigue resulted in
      veneer chipping, reproducing clinical findings allowing for investigations into
      the underlying causes of such failures.

PMID- 19407163
TI  - Science in the White House.

PMID- 19407164
TI  - Infectious diseases. As swine flu circles globe, scientists grapple with basic
      questions.

PMID- 19407165
TI  - Science and society. Hundreds gather for rally to defend animal research.

PMID- 19407166
TI  - Evolutionary genetics. Africans' deep genetic roots reveal their evolutionary
      story.

PMID- 19407167
TI  - Climate change. Study challenges cosmic ray-climate link.

PMID- 19407168
TI  - U.S. science policy. Obama courts a smitten audience at the national academy.

PMID- 19407170
TI  - Paleontology. 'Protein' in 80-million-year-old fossil bolsters controversial T.
      rex claim.

PMID- 19407172
TI  - Conflicts of interest. IOM panel backs public disclosure of drug company
      payments.

PMID- 19407173
TI  - Origins. On the origin of the immune system.

PMID- 19407174
TI  - Newsmaker interview. Defying skeptics, Richard Scheller thinks Genentech will
      thrive. Interview by Greg Miller.

PMID- 19407176
TI  - Astronomy. Herschel will open a new vista on infant stars and galaxies ...

PMID- 19407175
TI  - Astronomy...while Planck dusts the skies for the fingerprints of inflation.

PMID- 19407177
TI  - Biofuels. Corn-based ethanol flunks key test.

PMID- 19407178
TI  - American Association of Physical Anthropologists. Of tools and tubers.

PMID- 19407179
TI  - American Association of Physical Anthropologists. Civilization's cost: the
      decline and fall of human health.

PMID- 19407180
TI  - American Association of Physical Anthropologists. Reproductive fate versus
      environment.

PMID- 19407181
TI  - Confronting racism.

PMID- 19407182
TI  - Iraq study response lacks objectivity.

PMID- 19407183
TI  - Iraq study failed replication test.

PMID- 19407185
TI  - Ecology. Reducing the risks of the wildlife trade.

PMID- 19407186
TI  - History of science. Alexander von Humboldt and the general physics of the Earth.

PMID- 19407187
TI  - Planetary science. Magnetic twisters on Mercury.

PMID- 19407189
TI  - Climate. The geographic footprint of glacier change.

PMID- 19407188
TI  - Circadian rhythms. A circadian loop asSIRTs itself.

PMID- 19407190
TI  - Physics. A glassy state of supersolid helium.

PMID- 19407191
TI  - Cancer. Complicated supercomplexes.

PMID- 19407192
TI  - Medicine. Avoiding unintended toxicity.

PMID- 19407194
TI  - MESSENGER observations of magnetic reconnection in Mercury's magnetosphere.
AB  - Solar wind energy transfer to planetary magnetospheres and ionospheres is
      controlled by magnetic reconnection, a process that determines the degree of
      connectivity between the interplanetary magnetic field (IMF) and a planet's
      magnetic field. During MESSENGER's second flyby of Mercury, a steady southward
      IMF was observed and the magnetopause was threaded by a strong magnetic field,
      indicating a reconnection rate ~10 times that typical at Earth. Moreover, a large
      flux transfer event was observed in the magnetosheath, and a plasmoid and
      multiple traveling compression regions were observed in Mercury's magnetotail,
      all products of reconnection. These observations indicate that Mercury's
      magnetosphere is much more responsive to IMF direction and dominated by the
      effects of reconnection than that of Earth or the other magnetized planets.

PMID- 19407193
TI  - Neural mechanisms of a genome-wide supported psychosis variant.
AB  - Schizophrenia is a devastating, highly heritable brain disorder of unknown
      etiology. Recently, the first common genetic variant associated on a genome-wide
      level with schizophrenia and possibly bipolar disorder was discovered in ZNF804A
      (rs1344706). We show, by using an imaging genetics approach, that healthy
      carriers of rs1344706 risk genotypes exhibit no changes in regional activity but
      pronounced gene dosage-dependent alterations in functional coupling (correlated
      activity) of dorsolateral prefrontal cortex (DLPFC) across hemispheres and with
      hippocampus, mirroring findings in patients, and abnormal coupling of amygdala.
      Our findings establish disturbed connectivity as a neurogenetic risk mechanism
      for psychosis supported by genome-wide association, show that rs1344706 or
      variation in linkage disequilibrium is functional in human brain, and validate
      the intermediate phenotype strategy in psychiatry.

PMID- 19407195
TI  - MESSENGER observations of Mercury's exosphere: detection of magnesium and
      distribution of constituents.
AB  - Mercury is surrounded by a tenuous exosphere that is supplied primarily by the
      planet's surface materials and is known to contain sodium, potassium, and
      calcium. Observations by the Mercury Atmospheric and Surface Composition
      Spectrometer during MESSENGER's second Mercury flyby revealed the presence of
      neutral magnesium in the tail (anti-sunward) region of the exosphere, as well as
      differing spatial distributions of magnesium, calcium, and sodium atoms in both
      the tail and the nightside, near-planet exosphere. Analysis of these
      observations, supplemented by observations during the first Mercury flyby, as
      well as those by other MESSENGER instruments, suggests that the distinct spatial
      distributions arise from a combination of differences in source, transfer, and
      loss processes.

PMID- 19407196
TI  - The evolution of Mercury's crust: a global perspective from MESSENGER.
AB  - Mapping the distribution and extent of major terrain types on a planet's surface
      helps to constrain the origin and evolution of its crust. Together, MESSENGER and
      Mariner 10 observations of Mercury now provide a near-global look at the planet,
      revealing lateral and vertical heterogeneities in the color and thus composition
      of Mercury's crust. Smooth plains cover approximately 40% of the surface, and
      evidence for the volcanic origin of large expanses of plains suggests that a
      substantial portion of the crust originated volcanically. A low-reflectance,
      relatively blue component affects at least 15% of the surface and is concentrated
      in crater and basin ejecta. Its spectral characteristics and likely origin at
      depth are consistent with its apparent excavation from a lower crust or upper
      mantle enriched in iron- and titanium-bearing oxides.

PMID- 19407197
TI  - Evolution of the Rembrandt impact basin on Mercury.
AB  - MESSENGER's second Mercury flyby revealed a ~715-kilometer-diameter impact basin,
      the second-largest well-preserved basin-scale impact structure known on the
      planet. The Rembrandt basin is comparable in age to the Caloris basin, is
      partially flooded by volcanic plains, and displays a unique wheel-and-spoke-like
      pattern of basin-radial and basin-concentric wrinkle ridges and graben.
      Stratigraphic relations indicate a multistaged infilling and deformational
      history involving successive or overlapping phases of contractional and
      extensional deformation. The youngest deformation of the basin involved the
      formation of a approximately 1000-kilometer-long lobate scarp, a product of the
      global cooling and contraction of Mercury.

PMID- 19407198
TI  - High-frequency Holocene glacier fluctuations in New Zealand differ from the
      northern signature.
AB  - Understanding the timings of interhemispheric climate changes during the
      Holocene, along with their causes, remains a major problem of climate science.
      Here, we present a high-resolution 10Be chronology of glacier fluctuations in New
      Zealand's Southern Alps over the past 7000 years, including at least five events
      during the last millennium. The extents of glacier advances decreased from the
      middle to the late Holocene, in contrast with the Northern Hemisphere pattern.
      Several glacier advances occurred in New Zealand during classic northern warm
      periods. These findings point to the importance of regional driving and/or
      amplifying mechanisms. We suggest that atmospheric circulation changes in the
      southwest Pacific were one important factor in forcing high-frequency Holocene
      glacier fluctuations in New Zealand.

PMID- 19407200
TI  - A Gross-Pitaevskii treatment for supersolid helium.
AB  - Understanding the observations of nonlinear rotational susceptibility in samples
      of solid helium below temperatures of 1 to 200 millikelvin (mK) has been a
      subject of some controversy. Here, the observations are conjectured to be
      describable in terms of a rarified Gross-Pitaevskii superfluid of vacancies, with
      a transition temperature of about 50 mK, whose density is locally enhanced by
      crystal imperfections. The observations can be greatly affected by this density
      enhancement. I argue that every pure Bose solid's ground state is a supersolid.

PMID- 19407199
TI  - Biomolecular characterization and protein sequences of the Campanian hadrosaur B.
      canadensis.
AB  - Molecular preservation in non-avian dinosaurs is controversial. We present
      multiple lines of evidence that endogenous proteinaceous material is preserved in
      bone fragments and soft tissues from an 80-million-year-old Campanian hadrosaur,
      Brachylophosaurus canadensis [Museum of the Rockies (MOR) 2598]. Microstructural
      and immunological data are consistent with preservation of multiple bone matrix
      and vessel proteins, and phylogenetic analyses of Brachylophosaurus collagen
      sequenced by mass spectrometry robustly support the bird-dinosaur clade,
      consistent with an endogenous source for these collagen peptides. These data
      complement earlier results from Tyrannosaurus rex (MOR 1125) and confirm that
      molecular preservation in Cretaceous dinosaurs is not a unique event.

PMID- 19407201
TI  - Evidence for a superglass state in solid 4He.
AB  - Although solid helium-4 (4He) may be a supersolid, it also exhibits many
      phenomena unexpected in that context. We studied relaxation dynamics in the
      resonance frequency f(T) and dissipation D(T) of a torsional oscillator
      containing solid 4He. With the appearance of the "supersolid" state, the
      relaxation times within f(T) and D(T) began to increase rapidly together. More
      importantly, the relaxation processes in both D(T) and a component of f(T)
      exhibited a complex synchronized ultraslow evolution toward equilibrium. Analysis
      using a generalized rotational susceptibility revealed that, while exhibiting
      these apparently glassy dynamics, the phenomena were quantitatively inconsistent
      with a simple excitation freeze-out transition because the variation in f was far
      too large. One possibility is that amorphous solid 4He represents a new form of
      supersolid in which dynamical excitations within the solid control the superfluid
      phase stiffness.

PMID- 19407202
TI  - Competition for light causes plant biodiversity loss after eutrophication.
AB  - Human activities have increased the availability of nutrients in terrestrial and
      aquatic ecosystems. In grasslands, this eutrophication causes loss of plant
      species diversity, but the mechanism of this loss has been difficult to
      determine. Using experimental grassland plant communities, we found that addition
      of light to the grassland understory prevented the loss of biodiversity caused by
      eutrophication. There was no detectable role for competition for soil resources
      in diversity loss. Thus, competition for light is a major mechanism of plant
      diversity loss after eutrophication and explains the particular threat of
      eutrophication to plant diversity. Our conclusions have implications for
      grassland management and conservation policy and underscore the need to control
      nutrient enrichment if plant diversity is to be preserved.

PMID- 19407203
TI  - Burst spiking of a single cortical neuron modifies global brain state.
AB  - Different global patterns of brain activity are associated with distinct arousal
      and behavioral states of an animal, but how the brain rapidly switches between
      different states remains unclear. We here report that repetitive high-frequency
      burst spiking of a single rat cortical neuron could trigger a switch between the
      cortical states resembling slow-wave and rapid-eye-movement sleep. This is
      reflected in the switching of the membrane potential of the stimulated neuron
      from slow UP/DOWN oscillations to a persistent-UP state or vice versa, with
      concurrent changes in the temporal pattern of cortical local field potential
      (LFP) recorded several millimeters away. These results point to the power of
      single cortical neurons in modulating the behavioral state of an animal.

PMID- 19407204
TI  - Self-control in decision-making involves modulation of the vmPFC valuation
      system.
AB  - Every day, individuals make dozens of choices between an alternative with higher
      overall value and a more tempting but ultimately inferior option. Optimal
      decision-making requires self-control. We propose two hypotheses about the
      neurobiology of self-control: (i) Goal-directed decisions have their basis in a
      common value signal encoded in ventromedial prefrontal cortex (vmPFC), and (ii)
      exercising self-control involves the modulation of this value signal by
      dorsolateral prefrontal cortex (DLPFC). We used functional magnetic resonance
      imaging to monitor brain activity while dieters engaged in real decisions about
      food consumption. Activity in vmPFC was correlated with goal values regardless of
      the amount of self-control. It incorporated both taste and health in self
      controllers but only taste in non-self-controllers. Activity in DLPFC increased
      when subjects exercised self-control and correlated with activity in vmPFC.

PMID- 19407205
TI  - Exchange of genetic material between cells in plant tissue grafts.
AB  - Tissue grafting includes applications ranging from plant breeding to animal organ
      transplantation. Donor and recipient are generally believed to maintain their
      genetic integrity, in that the grafted tissues are joined but their genetic
      materials do not mix. We grafted tobacco plants from two transgenic lines
      carrying different marker and reporter genes in different cellular compartments,
      the nucleus and the plastid. Analysis of the graft sites revealed the frequent
      occurrence of cells harboring both antibiotic resistances and both fluorescent
      reporters. Our data demonstrate that plant grafting can result in the exchange of
      genetic information via either large DNA pieces or entire plastid genomes. This
      observation of novel combinations of genetic material has implications for
      grafting techniques and also provides a possible path for horizontal gene
      transfer.

PMID- 19407206
TI  - A cytidine deaminase edits C to U in transfer RNAs in Archaea.
AB  - All canonical transfer RNAs (tRNAs) have a uridine at position 8, involved in
      maintaining tRNA tertiary structure. However, the hyperthermophilic archaeon
      Methanopyrus kandleri harbors 30 (out of 34) tRNA genes with cytidine at position
      8. Here, we demonstrate C-to-U editing at this location in the tRNA's tertiary
      core, and present the crystal structure of a tRNA-specific cytidine deaminase,
      CDAT8, which has the cytidine deaminase domain linked to a tRNA-binding THUMP
      domain. CDAT8 is specific for C deamination at position 8, requires only the
      acceptor stem hairpin for activity, and belongs to a unique family within the
      "cytidine deaminase-like" superfamily. The presence of this C-to-U editing enzyme
      guarantees the proper folding and functionality of all M. kandleri tRNAs.

PMID- 19407207
TI  - A yeast hybrid provides insight into the evolution of gene expression regulation.
AB  - During evolution, novel phenotypes emerge through changes in gene expression, but
      the genetic basis is poorly understood. We compared the allele-specific
      expression of two yeast species and their hybrid, which allowed us to distinguish
      changes in regulatory sequences of the gene itself (cis) from changes in upstream
      regulatory factors (trans). Expression divergence between species was generally
      due to changes in cis. Divergence in trans reflected a differential response to
      the environment and explained the tendency of certain genes to diverge rapidly.
      Hybrid-specific expression, deviating from the parental range, occurred through
      novel cis-trans interactions or, more often, through modified trans regulation
      associated with environmental sensing. These results provide insights on the
      regulatory changes in cis and trans during the divergence of species and upon
      hybridization.

PMID- 19407210
TI  - Rapid diagnosis of sepsis and bacterial meningitis in children with real-time
      fluorescent quantitative polymerase chain reaction amplification in the bacterial
      16S rRNA gene.
AB  - A method for the detection of bacterial pathogens in sepsis and bacterial
      meningitis with 16S rRNA gene- based real-time fluorescent quantitative
      polymerase chain reaction (FQ-PCR) is developed. A total of 190 blood specimens
      and 5 cerebrospinal fluid specimens from neonates with suspected sepsis or
      bacterial meningitis were evaluated with 16S rRNA gene-based real-time FQ-PCR
      assay. The positive rate of the real-time FQ-PCR assay was significantly higher
      (25/195, 12.82%) than that of bacterial culture (15/195, 7.69%; P = .002). When
      bacterial culture was used as a control, the sensitivity of the real-time FQ-PCR
      was 100%, the specificity was 94.4%, and Youden's index was 0.944. This study
      suggests that 16S rRNA gene-based real-time FQ-PCR assay is an important and
      accurate method in the detection of bacterial pathogens of sepsis and bacterial
      meningitis and should have a promising usage in the diagnosis of sepsis and
      bacterial meningitis.

PMID- 19407209
TI  - The clinical course of childhood asthma in association with fever.
AB  - Little attention has been given to the relationship between fever and the
      severity of asthma. The authors studied 202 successive admissions of children
      with asthma over a period of 16 months to investigate the relationship between
      fever and the clinical course of asthma. There were 38 febrile children (18.8%),
      who were mostly younger than 5 years. Febrile children had a shorter mean
      hospital stay than afebrile children (1.7 vs 2.0 days). There were 25 episodes of
      acute severe asthma (13%): 2 among the 38 febrile children (5.2%), compared with
      23 episodes among the remaining 164 afebrile children (14%). Three children, who
      had very severe asthma requiring transfer to an intensive care unit, were
      afebrile. Radiological abnormalities (collapse/consolidation) occurred in 13
      cases: 3 from the febrile and 10 from the afebrile group. Monitoring body
      temperature is important in cases of asthma. Febrile children tend to be younger
      and are more likely to have a less severe clinical course of asthma.

PMID- 19407211
TI  - Early fatherhood: a mapping of the evidence base relating to pregnancy prevention
      and parenting support.
AB  - Teenage pregnancy prevention programmes targeted at young women have received
      considerable attention from researchers and programme developers. However, to
      date, relatively limited information is available on preventing teenage
      fatherhood or improving outcomes for young fathers. A notable gap is concerned
      with understanding the forms of sexual health programmes that are most effective
      from the perspective of young men. We conducted a systematic mapping to identify
      studies involving young men aimed at preventing teenage pregnancy, improving
      outcomes for teenage fathers or exploring the perspectives of young men around
      pregnancy and fatherhood. We searched a wide range of electronic databases from
      January 1996 to August 2008. Three quantitative and 15 qualitative studies were
      identified, of which nine were UK based. Key themes related to the
      inappropriateness of current sexual health promotion to respond to the needs of
      young men. While young men often possessed very similar ideals to young women,
      existing programmes were problematic when they negatively stereotyped young men
      and ineffectively addressed models of masculinity or the difficulties young men
      may have forming meaningful relationships. Further investigations are required on
      programme development for young men, particularly on sexual health promotion
      interventions for 'looked-after' young men and those from unstable childhoods.

PMID- 19407212
TI  - Discrete responses of myenteric neurons to structural and functional damage by
      neurotoxins in vitro.
AB  - Damage to the enteric nervous system is implicated in human disease and animal
      models of inflammatory bowel disease, diabetes, and Parkinson's disease, but the
      mechanism of death and the response of surviving neurons are poorly understood.
      We explored this in a coculture model of myenteric neurons, glia, and smooth
      muscle during exposure to the established or potential neurotoxins botulinum A,
      hydrogen peroxide, and acrylamide. Neuronal survival, axonal degeneration and
      regeneration, and neurotransmitter release were assessed during acute exposure (0
      24 h) to neurotoxin and subsequent recovery (96-144 h). Unique and selective
      responses to each neurotoxin were found with acrylamide (0.5-2.0 mM) causing a
      30% decrease in axon number without neuronal loss, whereas hydrogen peroxide (1
      200 microM) caused a parallel loss in both axon and neuron number. Immunoblotting
      identified the loss of synaptic vesicle proteins that paralleled axon damage and
      was associated with marked suppression of depolarization-induced release of
      acetylcholine (ACh). The caspase inhibitor zVAD, but not DEVD, significantly
      prevented neuronal death, implying a largely caspase-3/7-independent mechanism of
      apoptotic death that was supported by staining for annexin V and cleaved caspase
      3. In contrast, botulinum A (2 microg/ml) caused a 40% decrease in ACh release
      without effect on neuronal survival or axon structure. By 96 h after exposure to
      acrylamide or hydrogen peroxide, axon number was restored to or even surpassed
      the level of time-matched controls, regardless of partial neuronal loss, but ACh
      release remained markedly suppressed. Neural responses to toxic factors are
      initially unique but then converge upon robust axonal regeneration, whereas
      neurotransmitter release is both vulnerable to damage and slow to recover.

PMID- 19407213
TI  - Electrical stimulation of the mucosa evokes slow EPSPs mediated by NK1 tachykinin
      receptors and by P2Y1 purinoceptors in different myenteric neurons.
AB  - Slow excitatory postsynaptic potentials (EPSPs) in enteric neurons arise from
      diverse sources, but which neurotransmitters mediate specific types of slow EPSPs
      is unclear. We investigated transmitters and receptors mediating slow EPSPs in
      myenteric neurons evoked by electrical stimulation of the mucosa in guinea pig
      small intestine. Segments of ileum or jejunum were dissected to allow access to
      the myenteric plexus adjacent to intact mucosa, in vitro. AH and S neurons were
      impaled with conventional intracellular electrodes. Trains of stimuli delivered
      to the mucosa evoked slow EPSPs in AH neurons that were blocked or depressed by
      the neurokinin-1 (NK1) tachykinin antagonist SR140333 (100 nM) in 10 of 11
      neurons; the NK3 tachykinin receptor antagonist SR142801 (100 nM) had no effect
      on slow EPSPs in seven of nine AH neurons. Single pulses to the mucosa evoked
      fast EPSPs and slow depolarizations in S neurons. The depolarizations were
      divided into intermediate (durations 300-900 ms) or slow (durations 1.3-9 s)
      EPSPs. The slow EPSPs were blocked by pyridoxal phosphate-6-axophenyl-2-4
      disulfonic acid (30 microM, N = 3) or the specific P2Y(1) antagonist MRS 2179 (10
      microM, N = 6) and were predominantly in anally projecting S neurons that were
      immunoreactive for nitric oxide synthase (NOS). In contrast, intermediate EPSPs
      were predominantly evoked in NOS-negative neurons; these were abolished by MRS
      2179 (N = 8). Thus activation of pathways running from the mucosa excites three
      different types of slow EPSP in myenteric neurons, which are mediated by either a
      tachykinin (NK1, AH neurons) or a purine nucleotide (P2Y(1), S neurons).

PMID- 19407214
TI  - Intestinal ischemia-reperfusion injury: reversible and irreversible damage imaged
      in vivo.
AB  - The early events in an intestinal ischemic episode have been difficult to
      evaluate. Using in vivo microscopy we have analyzed in real-time the effects of
      short (15 min) and long (40-50 min) ischemia with subsequent reperfusion (IR),
      evaluating structure, integrity, and functioning of the mouse jejunal mucosa
      while monitoring blood flow by confocal microscopy. IR was imposed by
      inflation/deflation of a vascular occluder, and blood flow was monitored and
      confirmed with scanning confocal imaging. After short ischemia, villus tip cells
      revealed a rapid increase (23%) in the intracellular NAD(P)H concentration
      (confocal autofluorescence microscopy), and the pH-sensitive probe BCECF showed a
      biphasic response of the intracellular pH (pH(i)), quickly alkalinizing from the
      resting value of 6.8 +/- 0.1 to 7.1 +/- 0.1 but then strongly acidifying to 6.3
      +/- 0.1. Upon reperfusion, values returned toward control. In contrast, results
      were heterogeneous after long IR. During long ischemia, one-third of the
      epithelial cells remained viable with reversible changes upon reperfusion, but
      remaining cells lost membrane integrity (Lucifer Yellow uptake, LY) and had
      membrane blebs during ischemia. These effects became more pronounced as the
      reperfusion interval progressed when cells exhibited more severely affected
      NAD(P)H and pH(i) values, larger blebs, and more LY uptake and eventually were
      shed from the villus. Results from stereo microscopy suggest that these
      irreversible effects of IR may have occurred as a result of incomplete
      restorations of local blood flow, especially at the antimesenteric side of the
      intestine. We conclude that the adverse effects of short ischemia on the jejunum
      epithelium are fully reversible during the reperfusion interval. However, after
      long ischemia, reperfusion cannot restore normal structure and functioning of a
      majority of cells, which deteriorate further. Our results provide a basis for
      defining the cellular events that cause tissue to transit from reversible to
      irreversible damage during IR.

PMID- 19407215
TI  - Role of lysophosphatidylcholine in brush-border intestinal alkaline phosphatase
      release and restoration.
AB  - Intestinal alkaline phosphatase (IAP) is a brush-border membrane ectoenzyme (BBM
      IAP) that is released into the lumen (L-IAP) after a high-fat diet. We examined
      the effects of oil feeding and the addition of mixed-lipid micelles on the
      formation of L-IAP in oil-fed rat intestine, Caco-2 cell monolayers, and mouse
      intestinal loops. We localized IAP in the duodenum of rats fed corn oil using
      fluorescence microscopy with enzyme-labeled fluorescence-97 as substrate. Four
      hours after oil feeding, L-IAP increased approximately 10-fold accompanied by the
      loss of BBM-IAP, consistent with BBM-IAP release. Rat IAP isozyme mRNAs
      progressively increased 4-6 h after oil feeding, followed by the increase of IAP
      activity in the subapical location at 6 h, consistent with the restoration of IAP
      protein. Postprandial lipid-micelle components, sodium taurocholate with or
      without oleic acid, mono-oleylglycerol, cholesterol, or lysophosphatidylcholine
      (lysoPC) were applied singly or as mixed-lipid micelles to the apical surface of
      polarized Caco-2 cell monolayers. LysoPC increased L-IAP >10-fold over basal
      release. LysoPC released IAP into the apical medium more than other intestinal
      brush-border enzymes, 5'-nucleotidase, sucrase, aminopeptidase N, and lactase,
      without comparable lactate dehydrogenase release or cell injury. LysoPC increased
      human IAP mRNA levels by 1.5-fold in Caco-2 cells. Luminally applied lysoPC also
      increased release of IAP preferentially in mouse intestinal loops. These data
      show that lysoPC accelerates the formation of L-IAP from BBM-IAP, followed by
      enhanced IAP synthesis, suggesting the role that lysoPC might play in the
      turnover of brush-border proteins.

PMID- 19407216
TI  - Fibroblast growth factor receptor-3 regulates Paneth cell lineage allocation and
      accrual of epithelial stem cells during murine intestinal development.
AB  - Fibroblast growth factor receptor 3 (FGFR-3) is expressed in the lower crypt
      epithelium, where stem cells of the intestine reside. The role of FGFR-3
      signaling in regulating features of intestinal morphogenesis was examined in FGFR
      3-null (FGFR-3(-/-)) mice. FGFR-3(-/-) mice had only about half the number of
      intestinal crypts and a marked decrease in the number of functional clonogenic
      stem cells, as assessed by an in vivo microcolony-forming assay, compared with
      wild-type littermates. A marked deficit in allocation of progenitor cells to
      Paneth cell differentiation was noted, although all the principal epithelial
      lineages were represented in FGFR-3(-/-) mice. The total cellular content and
      nuclear localization of beta-catenin protein were reduced in FGFR-3(-/-) mice, as
      was expression of cyclin D1 and matrix metalloproteinase-7, major downstream
      targets of beta-catenin/T cell factor-4 (Tcf-4) signaling. Activation of FGFR-3
      in Caco-2 cells, an intestinal epithelial cell line, abrogated the fall in beta
      catenin/Tcf-4 signaling activity that is normally observed in these cells as
      cultures become progressively more confluent. These findings are consistent with
      the hypothesis that, during intestinal development, FGFR-3 signaling regulates
      crypt epithelial stem cell expansion and crypt morphogenesis, as well as Paneth
      cell lineage specification, through beta-catenin/Tcf-4-dependent and -independent
      pathways.

PMID- 19407217
TI  - Regulation of colonic apical potassium (BK) channels by cAMP and somatostatin.
AB  - High-conductance apical K+ (BK) channels are present in surface colonocytes of
      mammalian (including human) colon. Their location makes them well fitted to
      contribute to the excessive intestinal K(+) losses often associated with
      infective diarrhea. Since many channel proteins are regulated by phosphorylation,
      we evaluated the roles of protein kinase A (PKA) and phosphatases in the
      modulation of apical BK channel activity in surface colonocytes from rat distal
      colon using patch-clamp techniques, having first increased channel abundance by
      chronic dietary K+ enrichment. We found that PKA activation using 50 micromol/l
      forskolin and 5 mmol/l 3-isobutyl-1-methylxanthine stimulated BK channels in cell
      attached patches and the catalytic subunit of PKA (200 U/ml) had a similar effect
      in excised inside-out patches. The antidiarrheal peptide somatostatin (SOM; 2
      micromol/l) had a G protein-dependent inhibitory effect on BK channels in cell
      attached patches, which was unaffected by pretreatment with 10 micromol/l okadaic
      acid (an inhibitor of protein phosphatase type 1 and type 2A) but completely
      prevented by pretreatment with 100 micromol/l Na+ orthovanadate and 10 micromol/l
      BpV (inhibitors of phosphoprotein tyrosine phosphatase). SOM also inhibited
      apical BK channels in surface colonocytes in human distal colon. We conclude that
      cAMP-dependent PKA activates apical BK channels and may enhance colonic K+ losses
      in some cases of secretory diarrhea. SOM inhibits apical BK channels through a
      phosphoprotein tyrosine phosphatase-dependent mechanism, which could form the
      basis of new antidiarrheal strategies.

PMID- 19407218
TI  - Cortagine, a CRF1 agonist, induces stresslike alterations of colonic function and
      visceral hypersensitivity in rodents primarily through peripheral pathways.
AB  - Corticotropin-releasing factor (CRF) 1 receptor (CRF(1)) activation in the brain
      is a core pathway orchestrating the stress response. Anatomical data also support
      the existence of CRF signaling components within the colon. We investigated the
      colonic response to intraperitoneal (ip) injection of cortagine, a newly
      developed selective CRF(1) peptide agonist. Colonic motor function and visceral
      motor response (VMR) were monitored by using a modified miniaturized pressure
      transducer catheter in adult conscious male Sprague-Dawley rats and C57Bl/6 mice.
      Colonic permeability was monitored by the Evans blue method and myenteric neurons
      activation by Fos immunohistochemistry. Compared with vehicle, cortagine (10
      microg/kg ip) significantly decreased the distal colonic transit time by 45%
      without affecting gastric transit, increased distal and transverse colonic
      contractility by 35.6 and 66.2%, respectively, and induced a 7.1-fold increase in
      defecation and watery diarrhea in 50% of rats during the first hour postinjection
      whereas intracerebroventricular (icv) cortagine (3 microg/rat) had lesser
      effects. Intraperitoneal (ip) cortagine also increased colonic permeability,
      activated proximal and distal colonic myenteric neurons, and induced visceral
      hypersensitivity to a second set of phasic colorectal distention (CRD). The CRF
      antagonist astressin (10 mug/kg ip) abolished ip cortagine-induced hyperalgesia
      whereas injected icv it had no effect. In mice, cortagine (30 microg/kg ip)
      stimulated defecation by 7.8-fold, induced 60% incidence of diarrhea, and
      increased VMR to CRD. Stresslike colonic alterations induced by ip cortagine in
      rats and mice through restricted activation of peripheral CRF(1) receptors
      support a role for peripheral CRF(1) signaling as the local arm of the colonic
      response to stress.

PMID- 19407219
TI  - Effect of esophageal acid exposure on the cortical swallowing network in healthy
      human subjects.
AB  - Recent studies have demonstrated common cortical activity regions associated with
      esophageal acidification and swallowing. The effect of sensory signals imparted
      on these regions by esophageal acidification on swallow-related brain activity
      has physiological and clinical ramifications. Our aim in this study was to
      determine the effect of prior, unperceived esophageal acid exposure on cortical
      activity associated with swallowing. Functional magnetic resonance imaging (fMRI)
      techniques monitored brain activity associated with volitional swallowing before
      and after subliminal esophageal acid stimulation. Studies were carried out in two
      phases. In phase I (15 healthy, right-handed subjects, age 21-49 yr, 7 female)
      using whole brain imaging, we documented the potentiating effects of esophageal
      acidification alone on swallow-related cortical activity. In phase II (10
      healthy, right-handed subjects, age 20-54 yr, 5 female) using high-resolution
      fMRI, we measured swallow-induced regional brain activity within the cortical
      swallowing network before and after esophageal acidification. Unlike the phase I
      studies, we also tested the effect of saline perfusion alone on the cortical
      swallowing network in the phase II studies. Because of constraints imposed by
      high-resolution MRI for region-of-interest (ROI) analysis, we studied only the
      left hemisphere in this phase. None of the subjects developed heartburn during
      acid perfusion. In phase I, the number of swallow-induced activated voxels
      increased by 43% following esophageal acid stimulation (preacid, 44 +/- 3 voxels;
      postacid, 63 +/- 6 voxels; means +/- SE, P < 0.05) In phase II, contrary to
      saline perfusion, ROI analysis showed significantly increased regional swallow
      related fMRI activity volumes as well as percent maximum signal change after
      esophageal acid perfusion in cingulate, prefrontal, insula, and sensory/motor
      regions (P < 0.05). The precuneus showed no significant change. We concluded that
      subliminal esophageal acid stimulation has a potentiating effect on the cortical
      swallowing network in healthy individuals.

PMID- 19407220
TI  - Minireview: role of protein methylation and demethylation in nuclear hormone
      signaling.
AB  - Nuclear hormone receptors (NRs) are transcription factors responsible for
      mediating the biological effects of hormones during development, metabolism, and
      homeostasis. Induction of NR target genes is accomplished through the assembly of
      hormone-bound NR complexes at target promoters and coincides with changes in
      histone modifications that promote transcription. Some coactivators and
      corepressors of NR can enhance or inhibit NR function by covalently modifying
      histones. One such modification is methylation, which plays important roles in
      transcriptional regulation. Histone methylation is catalyzed by histone
      methyltransferases and reversed by histone demethylases. Recent studies have
      uncovered the importance of these enzymes in the regulation of NR target genes.
      In addition to histones, these enzymes have nonhistone substrates and can
      methylate and demethylate NRs and coregulatory proteins in order to modulate
      their function. This review discusses recent progress in our understanding of the
      role of methylation and demethylation of histones, NRs, and their coregulators in
      NR-mediated transcription.

PMID- 19407221
TI  - Thyroid hormone receptor mutations found in renal clear cell carcinomas alter
      corepressor release and reveal helix 12 as key determinant of corepressor
      specificity.
AB  - Thyroid hormone receptors (TRs) regulate multiple normal physiological and
      developmental pathways, whereas mutations in TRs can result in endocrine and
      neoplastic disease. A particularly high rate of TR mutations has been found in
      human renal clear cell carcinomas (RCCCs). We report here that the majority of
      these RCCC TR mutants tested are defective for transcriptional activation and
      behave as dominant-negative inhibitors of wild-type receptor function. Although
      several of the dominant-negative RCCC TR mutants are impaired for hormone
      binding, all fail to release from corepressors appropriately in response to T(3),
      a trait that closely correlates with their defective transcriptional properties.
      Notably, many of these mutants exhibit additional changes in their specificity
      for different corepressor splice forms that may further contribute to the disease
      phenotype. Mapping of the relevant mutations reveals that the C-terminal receptor
      helix 12 is not simply a hormone-operated switch that either permits or prevents
      all corepressor binding, but is instead a selective gatekeeper that actively
      discriminates between different forms of corepressor even in the absence of T(3).

PMID- 19407224
TI  - C-reactive protein and nitric oxide production in ischemic stroke.

PMID- 19407223
TI  - p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
AB  - Mammalian MafA/RIPE3b1 is an important glucose-responsive transcription factor
      that regulates function, maturation, and survival of beta-cells. Increased
      expression of MafA results in improved glucose-stimulated insulin secretion and
      beta-cell function. Because MafA is a highly phosphorylated protein, we examined
      whether regulating activity of protein kinases can increase MafA expression by
      enhancing its stability. We demonstrate that MafA protein stability in MIN6 cells
      and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase
      kinase 3. Inhibiting p38 MAPK enhanced MafA stability in cells grown under both
      low and high concentrations of glucose. We also show that the N-terminal domain
      of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous
      mutation of both threonines 57 and 134 into alanines in MafA was sufficient to
      prevent this degradation. Under oxidative stress, a condition detrimental to beta
      cell function, a decrease in MafA stability was associated with a concomitant
      increase in active p38 MAPK. Interestingly, inhibiting p38 MAPK but not glycogen
      synthase kinase 3 prevented oxidative stress-dependent degradation of MafA. These
      results suggest that the p38 MAPK pathway may represent a common mechanism for
      regulating MafA levels under oxidative stress and basal and stimulatory glucose
      concentrations. Therefore, preventing p38 MAPK-mediated degradation of MafA
      represents a novel approach to improve beta-cell function.

PMID- 19407222
TI  - Selective inhibition of prostaglandin E2 receptors EP2 and EP4 induces apoptosis
      of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and
      beta-catenin pathways and activation of intrinsic apoptotic mechanisms.
AB  - Endometriosis is a benign chronic gynecological disease of reproductive-age women
      characterized by the presence of functional endometrial tissues outside the
      uterine cavity. It is an estrogen-dependent disease. Current treatment modalities
      to inhibit biosynthesis and actions of estrogen compromise menstruation,
      pregnancy, and the reproductive health of women and fail to prevent reoccurrence
      of disease. There is a critical need to identify new specific signaling modules
      for non-estrogen-targeted therapies for endometriosis. In our previous study, we
      reported that selective inhibition of cyclooxygenase-2 prevented survival,
      migration, and invasion of human endometriotic epithelial and stromal cells,
      which was due to decreased prostaglandin E(2) (PGE(2)) production. In this study,
      we determined mechanisms through which PGE(2) promoted survival of human
      endometriotic cells. Results of the present study indicate that 1) PGE(2)
      promotes survival of human endometriotic cells through EP2 and EP4 receptors by
      activating ERK1/2, AKT, nuclear factor-kappaB, and beta-catenin signaling
      pathways; 2) selective inhibition of EP2 and EP4 suppresses these cell survival
      pathways and augments interactions between proapoptotic proteins (Bax and Bad)
      and antiapoptotic proteins (Bcl-2/Bcl-XL), facilitates the release of cytochrome
      c, and thus activates caspase-3/poly (ADP-ribose) polymerase-mediated intrinsic
      apoptotic pathways; and 3) these PGE(2) signaling components are more abundantly
      expressed in ectopic endometriosis tissues compared with eutopic endometrial
      tissues during the menstrual cycle in women. These novel findings may provide an
      important molecular framework for further evaluation of selective inhibition of
      EP2 and EP4 as potential therapy, including nonestrogen target, to expand the
      spectrum of currently available treatment options for endometriosis in women.

PMID- 19407225
TI  - Coated-platelet levels are low in patients with spontaneous intracerebral
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Coated-platelets are a subset of platelets with high
      procoagulant potential observed on dual agonist stimulation with collagen and
      thrombin. Failure to produce coated-platelets in animals results in a bleeding
      diathesis. With this background, we undertook a pilot study to investigate coated
      platelet production in patients with spontaneous intracerebral hemorrhage (SICH).
      METHODS: Coated-platelet levels were determined in 26 patients with a diagnosis
      of SICH and 52 controls. RESULTS: The patient population had significantly lower
      coated-platelet levels than the controls (mean+/-SD, 24.8+/-9.7% versus 32.9+/
      12.6%, P=0.0035). CONCLUSIONS: Decreased coated-platelet synthesis may be linked
      to the mechanisms involved in the events leading to SICH.

PMID- 19407226
TI  - Clinical-diffusion mismatch and benefit from thrombolysis 3 to 6 hours after
      acute stroke.
AB  - BACKGROUND AND PURPOSE: The clinical-diffusion mismatch (CDM) model has been
      proposed as a simpler tool than perfusion-diffusion mismatch (PDM) to select
      acute ischemic stroke patients for thrombolytic therapy. We hypothesized that in
      the 3- to 6-hour time window, the effect of tPA was significantly greater in
      patients with CDM than in patients without CDM. METHODS: This is a substudy of
      EPITHET, a double-blind multi-center study of 100 patients randomized to tPA or
      placebo 3 to 6 hours after stroke onset. MRI was obtained before treatment, and
      at 3 to 5 days and 90 days after treatment. Presence of PDM (perfusion
      deficit/DWI(volume) >1.2 and perfusion deficit at least 10 mL>DWI(volume)) and
      CDM (NIHSS >or=8 and DWI(volume) <or=25 mL) was determined for each patient. We
      assessed lesion growth and neurological improvement (decrease in NIHSS >or=8
      points between baseline and 90 days, or a 90-day NIHSS <or=1). RESULTS: 86% of
      the patients had PDM, but only 41% had CDM. CDM detected PDM with a sensitivity
      of 46% and a specificity of 86%. We found statistically significant effects of
      reperfusion on the rate of neurological improvement (OR 9.92, 95% CI 1.91 to
      51.64; P<0.01) and on absolute growth (difference: -59.60 mL, 95% CI -95.40 mL to
      -23.81 mL; P<0.01). Neither treatment with tPA nor reperfusion had a
      significantly different impact on lesion growth or clinical course in CDM
      patients compared to patients without CDM. CONCLUSIONS: There was no increased
      benefit from tPA in patients with CDM. The beneficial effects of reperfusion were
      similar in patients with and without CDM.

PMID- 19407227
TI  - Prior use of statins improves outcome in patients with intracerebral hemorrhage:
      prospective data from the National Acute Stroke Israeli Surveys (NASIS).
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a deadly form of
      stroke. Pretreatment with statins exerts protective effects in patients with
      ischemic stroke, but their effects in patients with ICH remains unclear. METHODS:
      The National Acute Stroke Israeli Surveys (NASIS) included all patients admitted
      with acute stroke to any of the 28 hospitals nationwide during February through
      March 2003 and March through April 2007. We compared stroke severity and outcomes
      of ICH patients who received statins before the index event with those who did
      not, using multivariable logistic regression models adjusting for the propensity
      to use statins before the event. RESULTS: Among 3212 stroke patients, 312 had ICH
      and 89 of them were receiving statins at the time of the ICH. Patients on statins
      before ICH had lower baseline NIHSS scores, less systemic complications, higher
      proportions of good outcome (modified Rankin scale 0 to 3), lower death rates,
      and higher rates of discharge home or to a rehabilitation facility. On logistic
      regression analyses statin use before the event was associated with odds ratios
      of 0.46 for having a severe stroke defined as baseline NIHSS >15 (95% CI; 0.23 to
      0.93), 2.97 for having good outcome (95% CI; 1.25 to 7.35) at discharge, and 0.25
      for death or nursing facility disposition (95% CI; 0.09 to 0.63). CONCLUSIONS:
      Use of statins before ICH is associated with reduced mortality and neurological
      disability and with a higher chance for good outcome, suggesting that statins may
      be protective in the setting of ICH.

PMID- 19407228
TI  - Causes and severity of ischemic stroke in patients with symptomatic intracranial
      arterial stenosis.
AB  - BACKGROUND AND PURPOSE: There are limited data on the causes and severity of
      subsequent stroke in patients presenting initially with TIA or stroke attributed
      to intracranial arterial stenosis. METHODS: We evaluated the location, type
      (lacunar vs nonlacunar), cause, and severity of stroke in patients who had an
      ischemic stroke endpoint in the Warfarin Aspirin Symptomatic Intracranial Disease
      (WASID) trial. RESULTS: Of the 569 patients enrolled in the WASID trial, 106
      patients (18.6%) had an ischemic stroke during a mean follow-up of 1.8 years.
      Stroke occurred in the territory of the symptomatic artery in 77 (73%) of 106
      patients. Among the 77 strokes in the territory, 70 (91%) were nonlacunar and 34
      (44%) were disabling. Stroke out of the territory of the symptomatic artery
      occurred in 29 (27%) of 106 patients. Among these 29 strokes, 24 (83%) were
      nonlacunar, 14 (48%) were attributed to previously asymptomatic intracranial
      stenosis, and 9 (31%) were disabling. CONCLUSIONS: Most subsequent strokes in
      patients with symptomatic intracranial artery stenosis are in the same territory
      and nonlacunar, and nearly half of the strokes in the territory are disabling.
      The most commonly identified cause of stroke out of the territory was a
      previously asymptomatic intracranial stenosis. Penetrating artery disease was
      responsible for a low number of strokes.

PMID- 19407229
TI  - Knowledge of tissue plasminogen activator for acute stroke among Michigan adults.
AB  - BACKGROUND AND PURPOSE: Although tissue plasminogen activator (tPA) is an
      effective therapy for acute ischemic stroke, treatment rates remain low. Efforts
      to address the underuse of tPA include public education to increase the
      recognition of stroke symptoms and the awareness of tPA treatment. Our objective
      was to determine the level of knowledge about tPA treatment for acute stroke
      among a representative sample of Michigan adults. METHODS: The Michigan
      Behavioral Risk Factor Survey (BRFS) is a random-digit-dial telephone survey of
      adults conducted annually as part of the national BRFS. Questions regarding tPA
      treatment for acute stroke were included in the 2004 Michigan BRFS. We examined
      the prevalence of awareness using chi(2) tests and generated multivariable
      logistic regression models. RESULTS: Among 4724 respondents, only 32.2% (95%
      CI=30.8 to 33.8%) were aware of the existence of tPA treatment for acute stroke,
      of whom 52.7% (50.0 to 55.4%) knew that it needed to be administered within 3
      hours of symptom onset. Awareness of tPA was higher among middle aged adults,
      females, whites, and those with higher education and income. Awareness of the
      time window for tPA was higher among middle aged adults and whites. CONCLUSIONS:
      In this population-based survey only a third of the public were aware of tPA as a
      treatment for stroke, and only 1 in 6 were aware that the treatment exists and
      needs to be given within 3 hours of symptom onset. Continuing efforts are
      necessary to increase public knowledge about tPA treatment for acute stroke.

PMID- 19407231
TI  - Effect of upper limb botulinum toxin injections on impairment, activity,
      participation, and quality of life among stroke patients.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to study the effect of
      Botulinum toxin type A (BoNT-A) injections in spastic upper limb muscles on
      impairment, activity, participation and quality of life in chronic stroke
      patients. METHODS: BoNT-A (Dysport) was injected into several upper limb spastic
      muscles in a group of 20 patients. Neurological impairment (muscle tone and
      strength, dexterity, SIAS), activity (ABILHAND), participation (SATIS-Stroke),
      and quality of life (SF36) were assessed before and 2 months after the
      injections. RESULTS: BoNT-A injections improved muscle tone, but had no impact on
      dexterity, manual ability, social participation, and quality of life.
      CONCLUSIONS: In this study, BoNT-A injections in spastic upper limbs
      significantly reduced neurological impairments, but had no functional impact.

PMID- 19407230
TI  - Problems and benefits reported by stroke family caregivers: results from a
      prospective epidemiological study.
AB  - BACKGROUND AND PURPOSE: Stroke symptoms can be very stressful for family
      caregivers, but most knowledge about the prevalence and stressfulness of stroke
      related patient problems is derived from convenience samples. In addition, little
      is known about perceived benefits of the stroke caregiving experience. The
      purpose of this study was to determine the prevalence and stressfulness of stroke
      related problems, and perceived benefits of caregiving, as reported by an
      epidemiologically derived sample of caregivers of stroke survivors. METHODS:
      Stroke survivors (N=75) from a prospective epidemiological study of stroke, the
      REasons for Geographic and Racial Differences in Stroke (REGARDS) study, and
      their family caregivers were followed. Caregivers were given a comprehensive
      telephone interview 8 to 12 months after the stroke, using measures of stroke
      patient problems, caregiver appraisals of the stressfulness of these problems,
      and perceived benefits of caregiving. RESULTS: Caregivers rated patient problems
      with mood (depression, loneliness and anxiety), memory, and physical care (bowel
      control), as the most stressful, but reported prevalence of these problems was
      lower than those reported previously in studies using clinical samples.
      Caregivers also reported many benefits from caregiving, with over 90% reporting
      that caregiving enabled them to appreciate life more. CONCLUSIONS:
      Epidemiologically based studies of stroke caregiving provide a unique picture of
      caregiver strains and benefits compared with clinical studies, which tend to over
      represent more impaired patients. Support for caregivers should include
      interventions to aid their coping with highly stressful mood, physical care, and
      cognitive problems of stroke patients, but should also attend to perceived
      benefits of caregiving.

PMID- 19407232
TI  - 4.5 hours: the new time window for tissue plasminogen activator in stroke.

PMID- 19407233
TI  - Acute blood pressure levels and neurological deterioration in different subtypes
      of ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine at which time
      points acute blood pressure (BP) was associated with neurological deterioration
      at 3 weeks in patients with ischemic stroke as a whole and in patients with
      different subtypes. METHODS: BP was measured every 6 hours for the first 36 hours
      of emergent hospitalization in 565 consecutive patients (347 men, 70+/-11 years
      in age) presenting within 24 hours of an acute ischemic stroke. Neurological
      deterioration was defined as a >or=2-point increase in the National Institutes of
      Health stroke scale (NIHSS) score at 3 weeks compared to the admission score.
      RESULTS: At 3 weeks, 64 patients (11.3%) had deteriorated neurologically. For the
      group as a whole, high systolic BP (SBP) values measured at 12, 18, 24, and 36
      hours postadmission were independently related to neurological deterioration
      after adjustment for age, sex, and known predictors, including admission NIHSS
      score, admission blood glucose level, and large infarct size. At 24 hours, the
      odds of neurological deterioration increased by 20% per 10-mm Hg increase in SBP.
      For cardioembolic stroke patients, high SBP values measured at 12 through 36
      hours were independently related to neurological deterioration after multivariate
      adjustment. For patients having stroke other than cardioembolism, no SBP values
      at any time point were related to neurological deterioration. CONCLUSIONS: Acute
      SBP values between 12 and 36 hours postadmission, but not those on admission or
      at 6 hours, were predictive of neurological deterioration within the initial 3
      weeks of ischemic stroke, particularly for cardioembolic stroke patients.

PMID- 19407234
TI  - Genetic determinants of white matter hyperintensities on brain scans: a
      systematic assessment of 19 candidate gene polymorphisms in 46 studies in 19,000
      subjects.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are highly heritable
      and associated with small artery ischemic stroke, so they may be a useful trait
      for studying the genetics of small vessel disease. Many studies have attempted to
      find associations between polymorphisms in various candidate genes and WMH. We
      aimed to evaluate the evidence for these associations by performing a systematic
      review and series of meta-analyses. METHODS: We used a comprehensive search
      strategy to identify studies of the association between any genetic polymorphism
      and WMH. For all polymorphisms in genes studied in >2000 subjects we performed
      meta-analyses, calculating pooled odds ratios or standardized mean differences.
      RESULTS: We identified 46 studies of polymorphisms in 19 genes in approximately
      19 000 subjects. Most genes were involved in lipid metabolism, control of
      vascular tone, or blood pressure regulation. Polymorphisms in the apolipoprotein
      E, angiotensin-converting enzyme, methylenetetrahydrofolate reductase, and
      angiotensinogen genes had been studied in >2000 subjects and were evaluated by
      meta-analysis. There was no evidence for an association between apolipoprotein E
      (epsilon 4+/-), methylenetetrahydrofolate reductase (677 cytosine/thymine
      polymorphism [C/T]), or angiotensinogen (Met235Thr) and WMH. For the angiotensin
      converting enzyme insertion/deletion polymorphism (I/D) there appeared to be a
      significant association (OR, 1.95; 95% CI, 1.09-3.48), but this may be partly
      attributable to the small study (mainly publication) and other biases.
      CONCLUSIONS: No genetic polymorphism has yet shown convincing evidence for an
      association with WMH. Much larger studies will be needed to detect and confirm
      genetic associations with this promising trait in the era of genome-wide
      association studies.

PMID- 19407235
TI  - Antiplatelet activity.

PMID- 19407236
TI  - Antiplatelet activity should be measured routinely: no.

PMID- 19407237
TI  - Need for a point-of-care assay for monitoring antiplatelet and antithrombotic
      therapies.

PMID- 19407238
TI  - Treatment of atherosclerotic intracranial arterial stenosis.

PMID- 19407239
TI  - Hypoxic preconditioning enhances the benefit of cardiac progenitor cell therapy
      for treatment of myocardial infarction by inducing CXCR4 expression.
AB  - Myocardial infarction rapidly depletes the endogenous cardiac progenitor cell
      pool, and the inefficient recruitment of exogenously administered progenitor
      cells limits the effectiveness of cardiac cell therapy. Recent reports indicate
      that interactions between the CXC chemokine stromal cell-derived factor 1 and its
      receptor CXC chemokine receptor 4 (CXCR4) critically mediate the ischemia-induced
      recruitment of bone marrow-derived circulating stem/progenitor cells, but the
      expression of CXCR4 in cardiac progenitor cells is very low. Here, we studied the
      influence of hypoxia on CXCR4 expression in cardiac progenitor cells, on the
      recruitment of intravenously administered cells to ischemic heart tissue, and on
      the preservation of heart function in a murine myocardial infarction model. We
      found that hypoxic preconditioning increased CXCR4 expression in CLK
      (cardiosphere-derived, Lin(-)c-kit(+) progenitor) cells and markedly augmented
      CLK cell migration (in vitro) and recruitment (in vivo) to the ischemic
      myocardium. Four weeks after surgically induced myocardial infarction, infarct
      size and heart function were significantly better in mice administered hypoxia
      preconditioned CLK cells than in mice treated with cells cultured under normoxic
      conditions. Furthermore, these effects were largely abolished by the addition of
      a CXCR4 inhibitor, indicating that the benefits of hypoxic preconditioning are
      mediated by the stromal cell-derived factor 1/CXCR4 axis, and that therapies
      targeting this axis may enhance cardiac-progenitor cell-based regenerative
      therapy.

PMID- 19407240
TI  - Regulation of oxygen distribution in tissues by endothelial nitric oxide.
AB  - Nitric oxide (NO) decreases cellular oxygen (O(2)) consumption by competitively
      inhibiting cytochrome c oxidase. Here, we show that endogenously released
      endothelial NO, either basal or stimulated, can modulate O(2) consumption both
      throughout the thickness of conductance vessels and in the microcirculation.
      Furthermore, we have shown that such modulation regulates O(2) distribution to
      the surrounding tissues. We have demonstrated these effects by measuring O(2)
      consumption in blood vessels in a hypoxic chamber and O(2) distribution in the
      microcirculation using the fluorescent oxygen-probe Ru(phen)(3)(2+). Removal of
      NO by physical or pharmacological means, or in eNOS(-/-) mice, abolishes this
      regulatory mechanism. Our results indicate that, in addition to its well-known
      effect on the regulation of vascular tone, endothelial NO plays a major role in
      facilitating the distribution of O(2), an action which is crucial for the
      adaptation of tissues, including the vessel wall itself, to hypoxia. It is
      possible that changes in the distribution of O(2) throughout the vessel wall may
      be implicated in the origin of vascular pathologies such as atherosclerosis.

PMID- 19407241
TI  - Genetically determined differences in sodium current characteristics modulate
      conduction disease severity in mice with cardiac sodium channelopathy.
AB  - Conduction slowing of the electric impulse that drives the heartbeat may evoke
      lethal cardiac arrhythmias. Mutations in SCN5A, which encodes the pore-forming
      cardiac sodium channel alpha subunit, are associated with familial arrhythmia
      syndromes based on conduction slowing. However, disease severity among mutation
      carriers is highly variable. We hypothesized that genetic modifiers underlie the
      variability in conduction slowing and disease severity. With the aim of
      identifying such modifiers, we studied the Scn5a(1798insD/+) mutation in 2
      distinct mouse strains, FVB/N and 129P2. In 129P2 mice, the mutation resulted in
      more severe conduction slowing particularly in the right ventricle (RV) compared
      to FVB/N. Pan-genomic mRNA expression profiling in the 2 mouse strains uncovered
      a drastic reduction in mRNA encoding the sodium channel auxiliary subunit beta4
      (Scn4b) in 129P2 mice compared to FVB/N. This corresponded to low to undetectable
      beta4 protein levels in 129P2 ventricular tissue, whereas abundant beta4 protein
      was detected in FVB/N. Sodium current measurements in isolated myocytes from the
      2 mouse strains indicated that sodium channel activation in myocytes from 129P2
      mice occurred at more positive potentials compared to FVB/N. Using computer
      simulations, this difference in activation kinetics was predicted to explain the
      observed differences in conduction disease severity between the 2 strains. In
      conclusion, genetically determined differences in sodium current characteristics
      on the myocyte level modulate disease severity in cardiac sodium channelopathies.
      In particular, the sodium channel subunit beta4 (SCN4B) may constitute a
      potential genetic modifier of conduction and cardiac sodium channel disease.

PMID- 19407242
TI  - Myc regulates embryonic vascular permeability and remodeling.
AB  - Previous work has shown that c-Myc is required for adequate vasculogenesis and
      angiogenesis. To further investigate the contribution of Myc to these processes,
      we conditionally expressed c-Myc in embryonic endothelial cells using a
      tetracycline-regulated system. Endothelial Myc overexpression resulted in severe
      defects in the embryonic vascular system. Myc-expressing embryos undergo
      widespread edema formation and multiple hemorrhagic lesions. They die between
      embryonic days 14.5 and 17.5. The changes in vascular permeability are not caused
      by deficiencies in vascular basement membrane composition or pericyte coverage.
      However, the overall turnover of endothelial cells is elevated as is revealed by
      increased levels of both proliferation and apoptosis. Whole-mount
      immunohistochemical analysis revealed alterations in the architecture of
      capillary networks. The dermal vasculature of Myc-expressing embryos is
      characterized by a reduction in vessel branching, which occurs despite
      upregulation of the proangiogenic factors vascular endothelial growth factor-A
      and angiopoietin-2. Thus, the net outcome of an excess of vascular endothelial
      growth factor-A and angiopoietin-2 in the face of an elevated cellular turnover
      appears to be a defect in vascular integrity.

PMID- 19407244
TI  - Notch signaling induces osteogenic differentiation and mineralization of vascular
      smooth muscle cells: role of Msx2 gene induction via Notch-RBP-Jk signaling.
AB  - OBJECTIVE: Vascular calcification is closely correlated with cardiovascular
      morbidity and mortality. Here, we demonstrate the role of Notch signaling in
      osteogenic differentiation and mineralization of vascular smooth muscle cells
      (SMCs). METHODS AND RESULTS: The Msx2 gene, a key regulator of osteogenesis, was
      highly induced by coculture with Notch ligand-expressing cells or overexpression
      of Notch intracellular domains (NICDs) in human aortic SMCs (HASMCs).
      Furthermore, the Notch1 intracellular domain (N1-ICD) overexpression markedly
      upregulated alkaline phosphatase (ALP) activity and matrix mineralization of
      HASMCs. A knockdown experiment with a small interfering RNA confirmed that Msx2
      mediated N1-ICD-induced osteogenic conversion of HASMCs. Interestingly, Msx2
      induction by N1-ICD was independent of bone morphogenetic protein-2 (BMP-2), an
      osteogenic morphogen upstream of Msx2. The transcriptional activity of the Msx2
      promoter was significantly enhanced by N1-ICD overexpression. The RBP-Jk binding
      element within the Msx2 promoter was critical to Notch-induced Msx2 gene
      expression. Correspondingly, N1-ICD overexpression did not induce the Msx2
      expression in RBP-Jk-deficient fibroblasts. Immunohistochemistry of human carotid
      artery specimens revealed localization of Notch1, Jagged1 and Msx2 to
      fibrocalcific atherosclerotic plaques. CONCLUSIONS: These results imply a new
      mechanism for osteogenic differentiation of vascular SMCs in which Notch/RBP-Jk
      signaling directly induces Msx2 gene expression and suggest its crucial role in
      mediating vascular calcification.

PMID- 19407243
TI  - Inactivation of the adenosine A2A receptor protects apolipoprotein E-deficient
      mice from atherosclerosis.
AB  - BACKGROUND: Atherosclerosis is a chronic inflammatory disease of the arterial
      vessel wall. The A(2A) receptor (A(2A)R) plays a central role in many
      antiinflammatory effects of adenosine. However, the role of A(2A)R in
      atherosclerosis is not clear. METHODS AND RESULTS: The knockout of A(2A)R in
      apolipoprotein E-deficient (Apoe(-/-)/A(2A)R(-/-)) mice led to an increase in
      body weight and levels of blood cholesterol and proinflammatory cytokines, as
      well as the inflammation status of atherosclerotic lesions. Unexpectedly, Apoe(-/
      )/A(2A)R(-/-) mice developed smaller lesions, as did chimeric Apoe(-/-) mice
      lacking A(2A)R in bone marrow-derived cells (BMDCs). The lesions of those mice
      exhibited a low density of foam cells and the homing ability of A(2A)R-deficient
      monocytes did not change. Increased foam cell apoptosis was detected in
      atherosclerotic lesions of Apoe(-/-)/A(2A)R(-/-) mice. In the absence of A(2A)R,
      macrophages incubated with oxidized LDL or in vivo-formed foam cells also
      exhibited increased apoptosis. A(2A)R deficiency in foam cells resulted in an
      increase in p38 mitogen-activated protein kinase (MAPK) activity. Inhibition of
      p38 phosphorylation abrogated the increased apoptosis of A(2A)R-deficient foam
      cells. CONCLUSIONS: Inactivation of A(2A)R, especially in BMDCs, inhibits the
      formation of atherosclerotic leisons, suggesting that A(2A)R inactivation may be
      useful for the treatment of atherosclerosis.

PMID- 19407245
TI  - Sonic Hedgehog induces Notch target gene expression in vascular smooth muscle
      cells via VEGF-A.
AB  - OBJECTIVE: Notch, VEGF, and components of the Hedgehog (Hh) signaling pathway
      have been implicated in vascular morphogenesis. The role of Notch in mediating
      hedgehog control of adult vascular smooth muscle cell (SMC) growth and survival
      remains unexplored. METHODS AND RESULTS: In cultured SMCs, activation of Hh
      signaling with recombinant rShh (3.5 mug/mL) or plasmid encoded Shh increased
      Ptc1 expression, enhanced SMC growth and survival and promoted Hairy-related
      transcription factor (Hrt) expression while concomitantly increasing VEGF-A
      levels. These effects were significantly reversed after Hh inhibition with
      cyclopamine. Shh-induced stimulation of Hrt-3 mRNA and SMC growth and survival
      was attenuated after inhibition of Notch-mediated CBF-1/RBP-Jk-dependent
      signaling with RPMS-1 while siRNA knockdown of Hrt-3 inhibited SMC growth and
      survival. Recombinant VEGF-A increased Hrt-3 mRNA levels while siRNA knockdown
      abolished rShh stimulated VEGF-A expression while concomitantly inhibiting Shh
      induced increases in Hrt-3 mRNA levels, proliferating cell nuclear antigen
      (PCNA), and Notch 1 IC expression, respectively. Hedgehog components were
      expressed within intimal SMCs of murine carotid arteries after vascular injury
      concomitant with a significant increase in mRNA for Ptc1, Gli(2), VEGF-A, Notch
      1, and Hrts. CONCLUSIONS: Hedgehog promotes a coordinate regulation of Notch
      target genes in adult SMCs via VEGF-A.

PMID- 19407247
TI  - Decreased muscle ACE activity enhances functional response to endurance training
      in rats, without change in muscle oxidative capacity or contractile phenotype.
AB  - In the present study, we tested the hypothesis that chronic ANG I-converting
      enzyme (ACE) inhibition could improve the training-induced improvement in
      endurance exercise performance and that this could be related to enhanced
      skeletal muscle metabolic efficiency. Female Wistar rats were assigned to four
      groups comprising animals either maintained sedentary or endurance trained (Sed
      and Tr, respectively), and treated or not for 10 wk with an ACE inhibitor,
      perindopril (2 mg.kg(-1).day(-1)) (Per and Ct, respectively) (n = 8 each).
      Trained rats underwent an 8-wk treadmill training protocol that consisted of 2
      h/day running at 30 m/min on a 8% decline. Before the start of and 1 wk before
      the end of experimental conditioning, the running time to exhaustion of rats was
      measured on a treadmill. The training program led to an increase in endurance
      time, higher in Tr-Per than in Tr-Ct group (125% in Tr-Ct vs. 183% in Tr-Per
      groups, P < 0.05). Oxidative capacity, measured in saponin-permeabilized fibers
      of slow soleus and fast plantaris muscles, increased with training, but less in
      Tr-Per than in Tr-Ct rats. The training-induced increase in citrate synthase
      activity also was less in soleus from Tr-Per than Tr-Ct rats. The training
      induced increase in the percentage of the type IIa isoform of myosin heavy chain
      (MHC) (45%, P < 0.05) and type IIx MHC (25%, P < 0.05) associated with decreased
      type IIb MHC (34%, P < 0.05) was minimized by perindopril administration. These
      findings demonstrate that the enhancement in physical performance observed in
      perindopril-treated animals cannot be explained by changes in mitochondrial
      respiration and/or MHC distribution within muscles involved in running exercise.

PMID- 19407248
TI  - Hyperinflation-induced cardiorespiratory failure in rats.
AB  - We previously showed that severe inspiratory resistive loads cause acute (<1 h)
      cardiorespiratory failure characterized by arterial hypotension, multifocal
      myocardial infarcts, and diaphragmatic fatigue. The mechanisms responsible for
      cardiovascular failure are unknown, but one factor may be the increased
      ventricular afterload caused by the large negative intrathoracic pressures
      generated when breathing against an inspiratory load. Because expiratory
      threshold loads increase intrathoracic pressure and decrease left ventricular
      afterload, we hypothesized that anesthetized rats forced to breathe against such
      a load would experience only diaphragmatic failure. Loading approximately doubled
      end-expiratory lung volume, halved respiratory frequency, and caused arterial
      hypoxemia and hypercapnia, respiratory acidosis, and increased inspiratory drive.
      Although hyperinflation immediately reduced the diaphragm's mechanical advantage,
      fatigue did not occur until near load termination. Mean arterial pressure
      progressively fell, becoming significant (cardiovascular failure) midway through
      loading despite tachycardia. Loading was terminated (endurance 125 +/- 43 min;
      range 82-206 min) when mean arterial pressure dropped below 50 mmHg. Blood
      samples taken immediately after load termination revealed hypoglycemia,
      hyperkalemia, and cardiac troponin T, the last indicating myocardial injury that
      was, according to histology, mainly in the right ventricle. This damage probably
      reflects a combination of decreased O(2) delivery (decreased venous return and
      arterial hypoxemia) and greater afterload due to hyperinflation-induced increase
      in pulmonary vascular resistance. Thus, in rats breathing at an increased end
      expiratory lung volume, cardiorespiratory, not just respiratory, failure still
      occurred. Right heart injury and dysfunction may contribute to the increased
      morbidity and mortality associated with acute exacerbations of obstructive airway
      disease.

PMID- 19407246
TI  - Fibronectin is an important regulator of flow-induced vascular remodeling.
AB  - OBJECTIVE: Fibronectin is an important regulator of cell migration,
      differentiation, growth, and survival. Our data show that fibronectin also plays
      an important role in regulating extracellular matrix (ECM) remodeling.
      Fibronectin circulates in the plasma and is also deposited into the ECM by a cell
      dependent process. To determine whether fibronectin affects vascular remodeling
      in vivo, we asked whether the fibronectin polymerization inhibitor, pUR4,
      inhibits intima-media thickening, and prevents excess ECM deposition in arteries
      using a mouse model of vascular remodeling. METHODS AND RESULTS: To induce
      vascular remodeling, partial ligation of the left external and internal carotid
      arteries was performed in mice. pUR4 and the control peptide were applied
      periadventitially in pluronic gel immediately after surgery. Animals were
      euthanized 7 or 14 days after surgery. Morphometric analysis demonstrated that
      the pUR4 fibronectin inhibitor reduced carotid intima (63%), media (27%), and
      adventitial thickening (40%) compared to the control peptide (III-11C). Treatment
      with pUR4 also resulted in a dramatic decrease in leukocyte infiltration into the
      vessel wall (80%), decreased ICAM-1 and VCAM-1 levels, inhibited cell
      proliferation (60% to 70%), and reduced fibronectin and collagen I accumulation
      in the vessel wall. In addition, the fibronectin inhibitor prevented SMC
      phenotypic modulation, as evidenced by the maintenance of smooth muscle (SM)
      alpha-actin and SM myosin heavy chain levels in medial cells. CONCLUSIONS: These
      data are the first to demonstrate that fibronectin plays an important role in
      regulating the vascular remodeling response. Collectively, these data suggest a
      therapeutic benefit of periadventitial pUR4 in reducing pathological vascular
      remodeling.

PMID- 19407249
TI  - Aging and muscle fiber type alter K+ channel contributions to the myogenic
      response in skeletal muscle arterioles.
AB  - Aging diminishes myogenic tone in arterioles from skeletal muscle. Recent
      evidence indicates that both large-conductance Ca2+-activated (BKCa) and voltage
      dependent (KV) K+ channels mediate negative feedback control of the myogenic
      response. Thus we tested the hypothesis that aging increases the contributions of
      KV and BKCa channels to myogenic regulation of vascular tone. Because myogenic
      responsiveness differs between oxidative and glycolytic muscles, we predicted
      that KV and BKCa channel contributions to myogenic responsiveness vary with fiber
      type. Myogenic responses of first-order arterioles from the gastrocnemius and
      soleus muscles of 4- and 24-mo-old Fischer 344 rats were evaluated in the
      presence and absence of 4-aminopyridine (5 mM) or iberiotoxin (30 nM), inhibitors
      of KV and BKCa, respectively. 4-Aminopyridine enhanced myogenic tone with aging
      and normalized age-related differences in both muscle types. By contrast,
      iberiotoxin eliminated age-related differences in soleus arterioles and had no
      effect in gastrocnemius vessels. KV1.5 is an integral component of KV channels in
      vascular smooth muscle; therefore, we determined the relative protein expression
      of KV1.5, as well as BKCa, in soleus and gastrocnemius arterioles. Immunoblot
      analysis revealed no differences in KV1.5 protein with aging or between variant
      fiber types, whereas BKCa protein levels declined with age in arterioles from
      both muscle groups. Collectively, these results suggest that the contribution of
      BKCa to myogenic regulation of vascular tone changes with age in soleus muscle
      arterioles, whereas increased KV channel expression and negative feedback
      regulation of myogenic tone increases with advancing age in arterioles from both
      oxidative and glycolytic muscles.

PMID- 19407250
TI  - Arterial and pulmonary arterial hemodynamics and oxygen delivery/extraction in
      normal humans exposed to hyperbaric air and oxygen.
AB  - Divers and hyperbaric chamber attendants breathe hyperbaric air routinely.
      Hyperbaric oxygen (HBO(2)) is used therapeutically frequently. Although much is
      understood about the hemodynamic physiology and gas exchange effects during
      hyperbaric air and HBO(2) exposure, arterial and pulmonary arterial (PA) catheter
      data, including blood gas values during hyperbaric air and HBO(2) exposure of
      normal humans, have not been reported. We exposed 10 healthy volunteers
      instrumented with arterial and PA catheters to air at 0.85, 3.0, 2.5, 2.0, 1.3
      (decompression stop), 1.12 (decompression stop), and 0.85 atm abs (our altitude)
      and then at identical pressures breathing O(2) followed by atmospheric pressure
      air while we measured arterial and PA pressures (PAP), cardiac output (Q), and
      blood gas measurements from both arterial and PA catheters. Although hemodynamic
      changes occurred during exposure to both hyperbaric air and HBO(2), we observed a
      greater magnitude of change under HBO(2) conditions: heart rate changes ranged
      from -9 to -19% (air to O(2)), respiratory rate from -12 to -17%, Q from -7 to 
      18%, PAP from -18 to -19%, pulmonary vascular resistance from -38 to -48%, and
      right-to-left shunt fraction from -87 to -107%. Mixed venous CO(2) fell 8% from
      baseline during HBO(2) despite mixed venous O(2) tensions of several hundred
      Torr. The stroke volume, O(2) delivery, and O(2) consumption did not change
      across exposures. The arterial and mixed venous partial pressures of O(2) and
      contents were elevated, as predicted. O(2) extraction increased 37% during
      HBO(2).

PMID- 19407252
TI  - Exhaled nitric oxide estimation by a simple and efficient noninvasive technique
      and its utility as a marker of airway inflammation in mice.
AB  - Allergic airway inflammation (AI) is commonly associated with enhanced exhaled
      nitric oxide (ENO) in both humans and mice. Since mouse models are being used to
      understand various mechanisms of asthma, a noninvasive, simple, and reproducible
      method to determine ENO in mice is required for serial nonterminal assessment
      that can be used independent of environmental situations in which the ambient air
      contains substantial amounts of NO as a contaminant. The aim of this study was to
      noninvasively measure ENO in individual mice and to test its utility as a marker
      of AI in different models of allergic AI. We modified the existing ENO measuring
      methods by incorporating flushing and washout steps that allowed simple but
      reliable measurements under highly variable ambient NO conditions (1-100 ppb).
      This method was used to serially follow ENO in acute and chronic models of
      allergic AI in mice. ENO was reproducibly measured by this modified method and
      was positively correlated to AI in both acute and chronic models of asthma but
      was not independently related to airway remodeling. Resolution of AI and other
      related parameters in dexamethasone-treated mice resulted in reduction of ENO,
      further confirming this association. Restriction of allergen challenge to
      pulmonary but not nasal airways was associated with a smaller increase in ENO
      compared with allergen challenge to both. Hence, ENO can now be reliably measured
      in mice independent of ambient NO levels and is a valid biomarker for AI.
      However, nasal and pulmonary airways are likely to be independent sources of ENO,
      and any results must be interpreted as such.

PMID- 19407251
TI  - Greater systemic lipolysis in women compared with men during moderate-dose
      infusion of epinephrine and/or norepinephrine.
AB  - Women have lower circulating catecholamine levels during metabolic perturbations,
      such as exercise or hypoglycemia, but similar rates of systemic lipolysis. This
      suggests women may be more sensitive to the lipolytic action of catecholamines,
      while maintaining similar glucoregulatory effects. The aim of the present study,
      therefore, was to determine whether women have higher rates of systemic lipolysis
      compared with men in response to matched peripheral infusion of catecholamines,
      but similar rates of glucose turnover. Healthy, nonobese women (n = 11) and men
      (n = 10) were recruited and studied on 3 separate days with the following
      infusions: epinephrine (Epi), norepinephrine (NE), or the two combined. Tracer
      infusions of glycerol and glucose were used to determine systemic lipolysis and
      glucose turnover, respectively. Following basal measurements of substrate
      kinetics, the catecholamine infusion commenced, and measures of substrate
      kinetics continued for 60 min. Catecholamine concentrations were similarly
      elevated in women and men during each infusion: Epi, 182-197 pg/ml and NE, 417
      507 pg/ml. There was a significant sex difference in glycerol rate of appearance
      and rate of disappearance with the catecholamine infusions (P < 0.0001), mainly
      due to a significantly greater glycerol turnover during the first 30 min of each
      infusion: glycerol rate of appearance during Epi was only 268 +/- 18 vs. 206 +/-
      21 micromol/min in women and men, respectively; during NE, only 173 +/- 13 vs.
      153 +/- 17 micromol/min, and during Epi+NE, 303 +/- 24 vs. 257 +/- 21
      micromol/min. No sex differences were observed in glucose kinetics under any
      condition. In conclusion, these data suggest that women are more sensitive to the
      lipolytic action of catecholamines, but have no difference in their
      glucoregulatory response. Thus the lower catcholamine levels observed in women
      vs. men during exercise and other metabolic perturbations may allow women to
      maintain a similar or greater level of lipid mobilization while minimizing
      changes in glucose turnover.

PMID- 19407255
TI  - Spinal NMDA receptor activation is necessary for de novo, but not the maintenance
      of, A2a receptor-mediated phrenic motor facilitation.
AB  - Adenosine 2a (A2a) receptor agonists elicit persistent increases in phrenic nerve
      activity by transactivating the neurotrophin receptor, TrkB, near phrenic
      motoneurons. Our working model proposes that A2a receptor-mediated TrkB receptor
      activation strengthens glutamatergic synapses onto phrenic motoneurons.
      Activation of glutamate N-methyl d-aspartate (NMDA) receptors has been implicated
      in other models of phrenic motor plasticity. Thus we hypothesized that NMDA
      receptor activation also would contribute to A2a receptor-mediated phrenic motor
      facilitation. Adult male Sprague-Dawley rats were anesthetized with urethane,
      mechanically ventilated, neuromuscularly paralyzed, and bilaterally vagotomized.
      The A2a receptor agonist CGS-21680 and the NMDA receptor-channel blocker MK-801
      were administered intrathecally over the C4 spinal segment. Phrenic nerve
      activity was recorded before, during, and after drug administration. MK-801
      (concentration range 0.1, 1.0, 10.0, and 100 microM) was administered 30 min
      before CGS-21680 (50 microM). MK-801 dose-dependently blocked A2a receptor
      mediated phrenic motor facilitation. When administered at 60 min post-CGS-21680,
      MK-801 prevented further increases in phrenic nerve activity compared with the
      CGS-21680 alone (CGS-21680 alone at 120 min: 114 +/- 19%; CGS-21680 and MK-801 at
      60 min post-CGS-21680: 61 +/- 11%, above baseline, P < 0.05) but did not return
      phrenic motor output to baseline values. Our data suggest that NMDA receptor
      activation is necessary for de novo A2a receptor-mediated phrenic motor
      facilitation and that the maintenance of preexisting phrenic motor facilitation
      does not involve NMDA receptor-dependent mechanisms.

PMID- 19407254
TI  - Airway wall attenuation: a biomarker of airway disease in subjects with COPD.
AB  - The computed tomographic (CT) densities of imaged structures are a function of
      the CT scanning protocol, the structure size, and the structure density. For
      objects that are of a dimension similar to the scanner point spread function, CT
      will underestimate true structure density. Prior investigation suggests that this
      process, termed contrast reduction, could be used to estimate the strength of
      thin structures, such as cortical bone. In this investigation, we endeavored to
      exploit this process to provide a CT-based measure of airway disease that can
      assess changes in airway wall thickening and density that may be associated with
      the mural remodeling process in subjects with chronic obstructive pulmonary
      disease (COPD). An initial computer-based study using a range of simulated airway
      wall sizes and densities suggested that CT measures of airway wall attenuation
      could detect changes in both wall thickness and structure density. A second
      phantom-based study was performed using a series of polycarbonate tubes of known
      density. The results of this again demonstrated the process of contrast reduction
      and further validated the computer-based simulation. Finally, measures of airway
      wall attenuation, wall thickness, and wall area (WA) divided by total cross
      sectional area, WA percent (WA%), were performed in a cohort of 224 subjects with
      COPD and correlated with spirometric measures of lung function. The results of
      this analysis demonstrated that wall attenuation is comparable to WA% in
      predicting lung function on univariate correlation and remain as a statistically
      significant correlate to the percent forced expiratory volume in 1 s predicted
      when adjusted for measures of both emphysema and WA%. These latter findings
      suggest that the quantitative assessment of airway wall attenuation may offer
      complementary information to WA% in characterizing airway disease in subjects
      with COPD.

PMID- 19407253
TI  - Effects of chronic hypoxia on soluble guanylate cyclase activity in fetal and
      adult ovine cerebral arteries.
AB  - A broad variety of evidence obtained largely in pulmonary vasculature suggests
      that chronic hypoxia modulates vasoreactivity to nitric oxide (NO). The present
      study explores the general hypothesis that chronic hypoxia also modulates
      cerebrovascular reactivity to NO, and does so by modulating the activity of
      soluble guanylate cyclase (sGC), the primary target for NO in vascular smooth
      muscle. Pregnant and nonpregnant ewes were maintained at either sea level or at
      3,820 m for the final 110 days of gestation, at which time middle cerebral
      arteries from term fetal lambs and nonpregnant adults were harvested. In both
      fetal and adult arteries, NO-induced vasodilatation was attenuated by chronic
      hypoxia and completely inhibited by 10 microM 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ), a selective inhibitor of sGC. sGC abundance (in ng
      sGC/mg protein) measured via Western immunoblots was approximately 10-fold
      greater in fetal (17.6 +/- 1.6) than adult (1.7 +/- 0.3) arteries but was not
      affected by chronic hypoxia. The specific activity of sGC (in pmol cGMP.microg
      sGC(-1).min(-1)) was similar in fetal (255 +/- 64) and adult (280 +/- 75)
      arteries and was inhibited by chronic hypoxia in both fetal (120 +/- 10) and
      adult (132 +/- 26) arteries. Rates of cGMP degradation (in pmol cGMP.mg protein(
      1).min(-1)) were similar in fetal (159 +/- 59) and adult (134 +/- 36) arteries
      but were not significantly depressed by chronic hypoxia in either fetal (115 +/-
      25) or adult (108 +/- 25) arteries. The cGMP analog 8-(p-chlorophenylthio)-cGMP
      was a more potent vasorelaxant in fetal (pD(2) = 4.7 +/- 0.1) than adult (pD(2) =
      4.3 +/- 0.1) arteries, but its ability to promote vasodilatation was not affected
      by chronic hypoxia in either age group. Together, these results reveal that
      hypoxic inhibition of NO-induced vasodilatation is attributable largely to
      attenuation of the specific activity of sGC and does not involve significant
      changes in sGC abundance, cGMP-phosphodiesterase activity, or the vasorelaxant
      activity of protein kinase G.

PMID- 19407256
TI  - Role of the respiratory muscles in acute respiratory failure of COPD: lessons
      from weaning failure.
AB  - It is problematic to withhold therapy in a patient with chronic obstructive
      pulmonary disease (COPD) who presents with acute respiratory failure so that
      detailed physiological measurements can be obtained. Accordingly, most
      information on respiratory muscle activity in patients experiencing acute
      respiratory failure has been acquired by studying patients who fail a trial of
      weaning after a period of mechanical ventilation. Such patients experience marked
      increases in inspiratory muscle load consequent to increases in resistance,
      elastance, and intrinsic positive end-expiratory pressure. Inspiratory muscle
      strength is reduced secondary to hyperinflation and possibly direct muscle damage
      and the release of inflammatory mediators. Most patients recruit both their
      sternomastoid and expiratory muscles, even though airflow limitation prevents the
      expiratory muscles from lowering lung volume. Even when acute hypercapnia is
      present, patients do not exhibit respiratory center depression; indeed, voluntary
      activation of the diaphragm, in absolute terms, is greater in hypercapnic
      patients than in normocapnic patients. Instead, the major mechanism of acute
      hypercapnia is the development of rapid shallow breathing. Despite the marked
      increase in mechanical load and decreased force-generating capacity of the
      inspiratory muscles, patients do not develop long-lasting muscle fatigue, at
      least over the period of a failed weaning trial. Although the disease originates
      within the lung parenchyma, much of the distress faced by patients with COPD,
      especially during acute respiratory failure, is caused by the burdens imposed on
      the respiratory muscles.

PMID- 19407257
TI  - A brief bout of exercise alters gene expression and distinct gene pathways in
      peripheral blood mononuclear cells of early- and late-pubertal females.
AB  - Recent studies show that brief exercise alters circulating neutrophil and
      peripheral blood mononuclear cell (PBMC) gene expression, ranging from cell
      growth to both pro-and anti-inflammatory processes. These initial observations
      were made solely in males, but whether PBMC gene expression is altered by
      exercise in females is not known. Ten early-pubertal girls (8-11 yr old) and 10
      late-pubertal girls (15-17 yr old) performed ten 2-min bouts of cycle ergometry (
      approximately 90% peak heart rate) interspersed with 1-min rest intervals. Blood
      was obtained at rest and after exercise, and microarrays were performed in each
      individual subject. RNA was hybridized to Affymetrix U133+2.0 Arrays. Exercise
      induced significant changes in PBMC gene expression in early (1,320 genes)- and
      late (877 genes)-pubertal girls. The expression of 622 genes changed similarly in
      both groups. Exercise influenced a variety of established gene pathways (EASE <
      0.04) in both older (6 pathways) and younger girls (11 pathways). Five pathways
      were the same in both groups and were functionally related to inflammation,
      stress, and apoptosis, such as natural killer cell-mediated cytotoxicity, antigen
      processing and presentation, B cell receptor signaling, and apoptosis. In
      summary, brief exercise alters PBMC gene expression in early- and late-pubertal
      girls. The pattern of change involves diverse genetic pathways, consistent with a
      global danger-type response, perhaps readying PBMCs for a range of physiological
      functions from inflammation to tissue repair that would be useful following a
      bout of physical activity.

PMID- 19407259
TI  - Expanded prediction equations of human sweat loss and water needs.
AB  - The Institute of Medicine expressed a need for improved sweating rate (msw)
      prediction models that calculate hourly and daily water needs based on metabolic
      rate, clothing, and environment. More than 25 years ago, the original Shapiro
      prediction equation (OSE) was formulated as msw (g.m(-2).h(-1))=27.9.Ereq.(Emax)(
      0.455), where Ereq is required evaporative heat loss and Emax is maximum
      evaporative power of the environment; OSE was developed for a limited set of
      environments, exposures times, and clothing systems. Recent evidence shows that
      OSE often overpredicts fluid needs. Our study developed a corrected OSE and a new
      msw prediction equation by using independent data sets from a wide range of
      environmental conditions, metabolic rates (rest to <or=450 W/m2), and variable
      exercise durations. Whole body sweat losses were carefully measured in 101
      volunteers (80 males and 21 females; >500 observations) by using a variety of
      metabolic rates over a range of environmental conditions (ambient temperature, 15
      46 degrees C; water vapor pressure, 0.27-4.45 kPa; wind speed, 0.4-2.5 m/s),
      clothing, and equipment combinations and durations (2-8 h). Data are expressed as
      grams per square meter per hour and were analyzed using fuzzy piecewise
      regression. OSE overpredicted sweating rates (P<0.003) compared with observed
      msw. Both the correction equation (OSEC), msw=147.exp (0.0012.OSE), and a new
      piecewise (PW) equation, msw=147+1.527.Ereq-0.87.Emax were derived, compared with
      OSE, and then cross-validated against independent data (21 males and 9 females;
      >200 observations). OSEC and PW were more accurate predictors of sweating rate
      (58 and 65% more accurate, P<0.01) and produced minimal error (standard error
      estimate<100 g.m(-2).h(-1)) for conditions both within and outside the original
      OSE domain of validity. The new equations provide for more accurate sweat
      predictions over a broader range of conditions with applications to public
      health, military, occupational, and sports medicine settings.

PMID- 19407258
TI  - Role of calcitonin gene-related peptide (CGRP) in ovine burn and smoke inhalation
      injury.
AB  - Concomitant smoke inhalation trauma in burn patients is a serious medical
      problem. Previous investigations in our sheep model revealed that these injuries
      lead to significant airway hyperemia, enhanced pulmonary fluid extravasation, and
      severely impaired pulmonary function. However, the pathophysiological mechanisms
      are still not fully understood. The lung is innervated by sensory nerves
      containing peptides such as substance P and calcitonin gene-related peptide.
      Noxious stimuli in the airways can induce a neurogenic inflammatory response,
      which has previously been implicated in several airway diseases. Calcitonin gene
      related peptide is known to be a potent vasodilator. We hypothesized that
      calcitonin gene-related peptide is also a mediator of the pulmonary reaction to
      toxic smoke and planned experiments to evaluate its role in this model. We tested
      the effects of pretreatment with a specific antagonist of the major receptor for
      calcitonin gene-related peptide (BIBN4096BS; 32 microg/kg, followed by continuous
      infusion of 6.4 microg.kg(-1).h(-1)) until the animal was killed 48 h after
      injury in an established ovine model of burn (40% total body surface, third
      degree) and smoke inhalation (48 breaths, <40 degrees C) injury. In treated
      animals (n = 7), the injury-related increases in tracheal blood flow and lung
      lymph flow were significantly attenuated compared with untreated controls (n =
      5). Furthermore, the treatment significantly attenuated abnormalities in
      respiratory gas exchange. The data suggest that calcitonin gene-related peptide
      contributes to early airway hyperemia, transvascular fluid flux, and respiratory
      malfunction following ovine burn and smoke inhalation injury. Future studies will
      be needed to clarify the potential therapeutic benefit for patients with this
      injury.

PMID- 19407260
TI  - L-2-Oxothiazolidine-4-carboxylate reverses glutathione oxidation and delays
      fatigue of skeletal muscle in vitro.
AB  - Fatiguing exercise promotes oxidation of intracellular thiols, notably
      glutathione. Interventions that oppose or reverse thiol oxidation can inhibit
      fatigue. The reduced cysteine donor l-2-oxothiazolidine-4-carboxylate (OTC)
      supports glutathione synthesis and is approved for use in humans but has not been
      evaluated for effects on skeletal muscle. We tested the hypotheses that OTC would
      1) increase reduced glutathione (GSH) levels and decrease oxidized glutathione,
      and 2) inhibit functional indexes of fatigue. Diaphragm fiber bundles from adult
      male ICR mice were incubated for 1 or 2 h at 37 degrees C with buffer (control,
      C) or OTC (10 mM). N-acetylcysteine (NAC; 10 mM) was used as a positive control.
      We measured GSH metabolites and fatigue characteristics. We found that muscle GSH
      content was increased after 1-h incubation with OTC or NAC but was not altered
      after 2-h incubation. One-hour treatment with OTC or NAC slowed the decline in
      force with repetitive stimulation [mean (SD) fatigue index at 300 s: OTC = 34 +/-
      6% vs. C = 50 +/- 8%, P < 0.05; NAC = 55 +/- 4% vs. C = 65 +/- 8%, P < 0.05] as
      did the 2-h OTC treatment (OTC = 38 +/- 9% vs. C = 51 +/- 9%, P < 0.05). These
      results demonstrate that OTC modulates the muscle GSH pool and opposes fatigue
      under the current experimental conditions.

PMID- 19407263
TI  - Convulsive therapy turns 75.
AB  - The Hungarian psychiatrist Laszlo Meduna was the first who induced epileptic fits
      to influence the course of mental illness. The following account, based on a
      review of Meduna's recently unearthed files and his writings, traces the
      beginnings of convulsive therapy.

PMID- 19407262
TI  - Randomized equivalence study evaluating the possibility of switching hemodialysis
      patients receiving subcutaneous human erythropoietin directly to intravenous
      darbepoetin alfa.
AB  - BACKGROUND: Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) used
      either intravenously or subcutaneously with no dose penalty; however, the direct
      switch from subcutaneous recombinant human erythropoietin (rHuEPO) to intravenous
      darbepoetin has barely been studied. OBJECTIVE: To establish the equivalence of a
      direct switch from subcutaneous rHuEPO to intravenous darbepoetin versus an
      indirect switch from subcutaneous rHuEPO to intravenous darbepoetin after 2
      months of subcutaneous darbepoetin in patients undergoing hemodialysis. METHODS:
      In this open, randomized, 6-month, prospective study, patients with end-stage
      kidney disease who were on hemodialysis were randomized into 2 groups: direct
      switch from subcutaneous rHuEPO to intravenous darbepoetin (group 1) and indirect
      switch from subcutaneous rHuEPO to intravenous darbepoetin after 2 months of
      subcutaneous darbepoetin (group 2). A third, nonrandomized group (control),
      consisting of patients treated with intravenous rHuEPO who were switched to
      intravenous darbepoetin, was also studied to reflect possible variations of
      hemoglobin (Hb) levels due to change from one type of ESA to the other. The
      primary outcome was the proportion of patients with stable Hb levels at month 6.
      Secondary endpoints included Hb stability at month 3, dosage requirements for
      darbepoetin, and safety of the administration route. RESULTS: Among 154
      randomized patients, the percentages with stable Hb levels were equivalent in
      groups 1 and 2, respectively, at month 3 (86.0% vs 91.3%) and month 6 (82.1% vs
      81.6%; difference -0.5 [90% CI -12.8 to 11.8]). Mean Hb levels between baseline
      and month 6 remained stable in both groups, with no variation in mean darbepoetin
      dose. Mean ferritin levels remained above 100 microg/L in the 3 groups during the
      whole study, and darbepoetin was well tolerated. CONCLUSIONS: This study has
      shown equivalent efficacy on Hb stability without the need for dosage increase in
      patients switched directly from subcutaneous rHuEPO to intravenous darbepoetin.

PMID- 19407261
TI  - Benefits and harms of erythropoiesis-stimulating agents for anemia related to
      cancer: a meta-analysis.
AB  - BACKGROUND: Erythropoiesis-stimulating agents are used to treat anemia in
      patients with cancer. However, their safety and effectiveness is controversial.
      We did a systematic review of the clinical efficacy and harms of these agents in
      adults with anemia related to cancer or chemotherapy. METHODS: We conducted a
      systematic review of published and unpublished randomized controlled trials
      (RCTs) using accepted methods for literature searches, article selection, data
      extraction and quality assessment. We included RCTs involving anemic adults with
      cancer. We compared the use of erythropoiesis-stimulating agents with nonuse and
      assessed clinical outcomes (all-cause mortality, cardiovascular events and
      hypertension, health-related quality of life, blood transfusions and tumour
      response) and harms (serious adverse events) between groups. RESULTS: We
      identified 52 trials (n = 12 006) that met our selection criteria. The pooled all
      cause mortality during treatment was significantly higher in the group receiving
      erythropoiesis-stimulating therapy than in the control group (relative risk [RR]
      1.15, 95% confidence interval [CI] 1.03 to 1.29). Compared with no treatment, use
      of erythropoiesis-stimulating agents led to clinically detectable improvements in
      disease-specific measures of quality of life. It also reduced the use of blood
      transfusions (RR 0.64, 95% CI 0.56 to 0.73). However, it led to an increased risk
      of thrombotic events (RR 1.69, 95% CI 1.27 to 2.24) and serious adverse events
      (RR 1.16, 95% CI 1.08 to 1.25). INTERPRETATION: Use of erythropoiesis-stimulating
      agents in patients with cancer-related anemia improved some disease-specific
      measures of quality of life and decreased the use of blood transfusions. However,
      it increased the risk of death and serious adverse events. Our findings suggest
      that such therapy not be used routinely as an alternative to blood transfusion in
      patients with anemia related to cancer.

PMID- 19407264
TI  - Accountability of specialist child and adolescent mental health services.
AB  - Outcome auditing of specialist child and adolescent mental health services
      (CAMHS) is now well under way internationally. There is, however, debate about
      objectives and tools. A case is made for the achievable goal of enhancing service
      accountability through user satisfaction information and clinician-rated
      contextualised measures of improvements in symptoms and impairment.

PMID- 19407266
TI  - Family relationships in childhood and common psychiatric disorders in later life:
      systematic review of prospective studies.
AB  - BACKGROUND: Most evidence for associations between childhood adversity and adult
      mental illness is retrospective. AIMS: To evaluate prospective evidence of
      associations between poor parent-child relationships and common psychiatric
      disorders in later life. METHOD: Systematic review of studies published between
      1970 and 2008 including: (a) more than 100 participants; (b) measures of
      relationships in the home during childhood; (c) at least 10 years between
      assessment of exposures; and (d) measures of anxiety, depression, suicide,
      suicidal ideation or post-traumatic stress disorder (PTSD). Analysis was by
      narrative synthesis. RESULTS: Twenty-three papers were identified reporting data
      from 16 cohorts. Abusive relationships predicted depression, anxiety and PTSD.
      Maternal emotional unavailability in early life predicted suicide attempts in
      adolescence. Results of studies investigating less severe relationship problems
      were suggestive but not conclusive of causal association, due partly to
      methodological heterogeneity. CONCLUSIONS: Given the prevalence and disabling
      nature of common psychiatric problems, these studies highlight the need to
      minimise harm associated with dysfunctional parent-child relationships.

PMID- 19407268
TI  - Screening for depression in high-risk groups: prospective cohort study in general
      practice.
AB  - BACKGROUND: Currently only about half of the people who have major depressive
      disorder are detected during regular health care. Screening in high-risk groups
      might be a possible solution. AIMS: To evaluate the effectiveness of selective
      screening for major depressive disorder in three high-risk groups in primary
      care: people with mental health problems, people with unexplained somatic
      complaints and people who frequently attend their general practitioner. METHOD:
      Prospective cohort study among 2005 people in high-risk groups in three health
      centres in The Netherlands. RESULTS: Of the 2005 people identified, 1687 were
      invited for screening and of these 780 participated. Screening disclosed 71
      people with major depressive disorder: 36 (50.7%) already received treatment, 14
      (19.7%) refused treatment and 4 individuals did not show up for an appointment.
      As a final result of the screening, 17 individuals (1% of 1687) started treatment
      for major depressive disorder. CONCLUSIONS: Screening for depression in high-risk
      populations does not seem to be effective, mainly because of the low rates of
      treatment initiation, even if treatment is freely and easily accessible.

PMID- 19407269
TI  - Issues concerning feedback about genetic testing and risk of depression.
AB  - BACKGROUND: Recent studies show that adverse life events have a significantly
      greater impact on depression onset for those with the s/s allele of the genotype
      for the 5-HT gene-linked promoter region. Research in genes related to risk of
      depression leads to the question of how this information is received by
      individuals. AIMS: To investigate factors related to the response to receiving
      one's own serotonin transporter genotype results. METHOD: Predictors of the
      impact of receiving individual genotype data were assessed in 128 participants in
      a study of gene-environment interaction in depression onset. RESULTS: Two-thirds
      decided to learn their individual genotype results (receivers) and prior to
      disclosure this decision was associated with a perception of greater benefit from
      receipt of the information (P=0.001). Receivers completing the 2-week (n=76) and
      3-month follow-up (n=78) generally reported feeling pleased with the information
      and having had a more positive experience than distress. However, distress was
      related to genotype, with those with the s/s allele being most affected.
      CONCLUSIONS: There was high interest in, and satisfaction with, learning about
      one's serotonin transporter genotype. Participants appeared to understand that
      the gene conferred susceptibility to depression rather than a direct causal
      effect.

PMID- 19407271
TI  - Psychosis and autism: magnetic resonance imaging study of brain anatomy.
AB  - BACKGROUND: Autism-spectrum disorder is increasingly recognised, with recent
      studies estimating that 1% of children in South London are affected. However, the
      biology of comorbid mental health problems in people with autism-spectrum
      disorder is poorly understood. AIMS: To investigate the brain anatomy of people
      with autism-spectrum disorder with and without psychosis. METHOD: We used in vivo
      magnetic resonance imaging and compared 30 adults with autism-spectrum disorder
      (14 with a history psychosis) and 16 healthy controls. RESULTS: Compared with
      controls both autism-spectrum disorder groups had significantly less grey matter
      bilaterally in the temporal lobes and the cerebellum. In contrast, they had
      increased grey matter in striatal regions. However, those with psychosis also had
      a significant reduction in grey matter content of frontal and occipital regions.
      Contrary to our expectation, within autism-spectrum disorder, comparisons
      revealed that psychosis was associated with a reduction in grey matter of the
      right insular cortex and bilaterally in the cerebellum extending into the
      fusiform gyrus and the lingual gyrus. CONCLUSIONS: The presence of
      neurodevelopmental abnormalities normally associated with autism-spectrum
      disorder might represent an alternative 'entry-point' into a final common pathway
      of psychosis.

PMID- 19407270
TI  - Mental disorders and termination of education in high-income and low- and middle
      income countries: epidemiological study.
AB  - BACKGROUND: Studies of the impact of mental disorders on educational attainment
      are rare in both high-income and low- and middle-income (LAMI) countries. AIMS:
      To examine the association between early-onset mental disorder and subsequent
      termination of education. METHOD: Sixteen countries taking part in the World
      Health Organization World Mental Health Survey Initiative were surveyed with the
      Composite International Diagnostic Interview (n=41 688). Survival models were
      used to estimate associations between DSM-IV mental disorders and subsequent non
      attainment of educational milestones. RESULTS: In high-income countries, prior
      substance use disorders were associated with non-completion at all stages of
      education (OR 1.4-15.2). Anxiety disorders (OR=1.3), mood disorders (OR=1.4) and
      impulse control disorders (OR=2.2) were associated with early termination of
      secondary education. In LAMI countries, impulse control disorders (OR=1.3) and
      substance use disorders (OR=1.5) were associated with early termination of
      secondary education. CONCLUSIONS: Onset of mental disorder and subsequent non
      completion of education are consistently associated in both high-income and LAMI
      countries.

PMID- 19407272
TI  - Anterior cingulate cortex abnormalities associated with a first psychotic episode
      in bipolar disorder.
AB  - BACKGROUND: The anterior cingulate cortex is frequently implicated in the
      pathophysiology of bipolar disorder, but magnetic resonance imaging (MRI) studies
      have reported variable findings owing to a reliance on patient samples with
      chronic illness and to limited appreciation of the region's heterogeneity. AIMS:
      To characterise anterior cingulate cortex abnormalities in patients with bipolar
      disorder experiencing their first episode of psychosis while accounting for
      regional anatomical variability. METHOD: Grey matter volume, surface area and
      cortical thickness were measured in six anterior cingulate cortex subregions per
      hemisphere using MRI scans acquired from 26 patients with bipolar I disorder
      experiencing first-episode psychosis and 26 healthy controls matched for age,
      gender and regional morphological variability. RESULTS: Relative to controls,
      male patients displayed increased thickness in the right subcallosal limbic
      anterior cingulate cortex. No significant differences were identified in females
      for grey matter volume or surface area measures. The findings were not
      attributable to medication effects. CONCLUSIONS: These data suggest that first
      episode psychosis in bipolar disorder is associated with a gender-specific, right
      lateralised thickness increase in anterior cingulate cortex subregions known to
      play a role in regulating physiological stress responses.

PMID- 19407274
TI  - Cognitive effectiveness of olanzapine and risperidone in first-episode psychosis.
AB  - BACKGROUND: Cognitive impairment in schizophrenia-spectrum disorders is highly
      prevalent and notably influences functional outcomes. AIMS: To characterise the
      cognitive effectiveness of second-generation antipsychotic drugs. METHOD: One
      hundred consecutive and previously unmedicated patients with first-episode
      schizophrenia-spectrum disorders were admitted. Seventy-seven completed baseline,
      1-month and 6-month psychopathological and neuropsychological assessments.
      Patients were randomised to risperidone or olanzapine treatment. Four final
      treatment allocation groups were defined since patients continued treatment in
      their normal setting: risperidone, olanzapine, mixed and no-antipsychotic groups.
      RESULTS: There were no differences in cognitive effectiveness between the four
      treatment groups. Reliable change index methods demonstrated that nearly a half
      of patients showed an improvement in Global Cognitive Score at the 6-month
      assessment. Improvement on the neuropsychological tests ranged from 17 to 54%. A
      strong predictor of cognitive response was poor performance on baseline
      neuropsychological tests; response was moderately influenced by a low premorbid
      scholastic performance and IQ. CONCLUSIONS: Cognitive improvement related to
      second-generation antipsychotic drugs appeared within the first 4 weeks of
      treatment and persisted at 6 months irrespective of treatment group. Greater
      cognitive dysfunction at baseline and lower premorbid cognitive background
      predicted cognitive improvement in our sample.

PMID- 19407273
TI  - Metabolic profile of antipsychotic-naive individuals with non-affective
      psychosis.
AB  - BACKGROUND: Some studies suggest individuals with schizophrenia have an increased
      risk of diabetes prior to antipsychotic use. Small sample sizes and the potential
      for confounding by hypercortisolaemia have decreased confidence in those results.
      AIMS: To examine diabetes-related factors in newly diagnosed, antipsychotic-naive
      people with non-affective psychosis. METHOD: Participants with psychosis (the
      psychosis group; n = 50) and matched controls (the control group; n = 50) were
      given a 2 h oral glucose tolerance test. Fasting concentrations were also
      determined for adiponectin, interleukin-6 and C-reactive protein. RESULTS:
      Compared with the control group, the psychosis group had significant increases in
      2 h glucose and interleukin-6 concentrations, and in the prevalence of abnormal
      glucose tolerance (16% of psychosis group v. 0% of control group). Adiponectin
      and C-reactive protein concentrations did not differ significantly between the
      two groups. These findings could not be attributed to differences in cortisol
      concentrations, smoking, gender, neighbourhood of residence, body mass index,
      aerobic conditioning, ethnicity, socioeconomic status or age. CONCLUSIONS:
      Individuals with non-affective psychosis appear to have an increased prevalence
      of abnormal glucose tolerance prior to antipsychotic treatment, as well as
      abnormalities in a related inflammatory molecule. These underlying problems may
      contribute to the metabolic side-effects of antipsychotic medications.

PMID- 19407276
TI  - Development and implementation of early intervention services for young people
      with psychosis: case study.
AB  - BACKGROUND: The development of early intervention services for young people with
      first-episode psychosis is a priority internationally. AIMS: To evaluate the
      development, implementation and impact of existing and newly formed early
      intervention services in England. METHOD: Multiple-case study involving staff,
      users, carers and commissioners of 14 early intervention services. RESULTS:
      Service numbers increased in response to national policy directives. They were
      still actively working with 90.6% of service users 12 months after inception.
      They were highly valued by users and carers as providing a personal service that
      contrasted with previous experiences of care. Tensions between providing a
      quality service and meeting case-load targets linked to future funding led teams
      to adopt a series of survival strategies with some unintended consequences.
      CONCLUSIONS: Early intervention services are highly valued by consumers and
      engage users effectively after 12 months. Implementation of these services is
      threatened unless sufficient consistent funding is made available.

PMID- 19407277
TI  - Stalking among juveniles.
AB  - BACKGROUND: There is an almost total lack of empirical research on stalking among
      juveniles. AIMS: To examine the characteristics, nature and impacts of stalking
      by juveniles. METHOD: Analysis of consecutive court applications for a
      restraining order against a juvenile because of stalking behaviours. RESULTS: A
      total of 299 juvenile stalkers were identified. The majority were male (64%) and
      their victims predominantly female (69%). Most pursued a previously known victim
      (98%), favouring direct means of contact via unwanted approaches (76%) and
      telephone calls or text messaging (67%). Threats (75%) and physical and sexual
      assaults (54%) were common. The contexts for juvenile stalking involved an
      extension of bullying (28%), retaliation for a perceived harm (22%), a reaction
      to rejection (22%), sexual predation (5%) and infatuation (2%). CONCLUSIONS:
      Juvenile stalking is characterised by direct, intense, overtly threatening and
      all too often violent forms of pursuit. The seriousness that is afforded to adult
      forms of stalking should similarly apply to this behaviour among juveniles given
      the even greater rates of disruption to the victim's life and risks of being
      attacked.

PMID- 19407278
TI  - In-patient and residential alternatives to standard acute psychiatric wards in
      England.
AB  - BACKGROUND: Acute psychiatric wards have been the focus of widespread
      dissatisfaction. Residential alternatives have attracted much interest, but
      little research, over the past 50 years. AIMS: Our aims were to identify all in
      patient and residential alternatives to standard acute psychiatric wards in
      England, to develop a typology of such services and to describe their
      distribution and clinical populations. METHOD: National cross-sectional survey of
      alternatives to standard acute in-patient care. RESULTS: We found 131 services
      intended as alternatives. Most were hospital-based and situated in deprived
      areas, and about half were established after 2000. Several clusters with
      distinctive characteristics were identified, ranging from general acute wards
      applying innovative therapeutic models, through clinical crisis houses that are
      highly integrated with local health systems, to more radical voluntary sector
      alternatives. Most people using the alternatives had a previous history of
      admission, but only a few community-based services accepted compulsory
      admissions. CONCLUSIONS: Alternatives to standard acute psychiatric wards
      represent an important, but previously undocumented and unevaluated, sector of
      the mental health economy. Further evidence is needed to assess whether they can
      improve the quality of acute in-patient care.

PMID- 19407280
TI  - Lithium levels in drinking water and risk of suicide.
AB  - Although lithium is known to prevent suicide in people with mood disorders, it is
      uncertain whether lithium in drinking water could also help lower the risk in the
      general population. To investigate this, we examined lithium levels in tap water
      in the 18 municipalities of Oita prefecture in Japan in relation to the suicide
      standardised mortality ratio (SMR) in each municipality. We found that lithium
      levels were significantly and negatively associated with SMR averages for 2002
      2006. These findings suggest that even very low levels of lithium in drinking
      water may play a role in reducing suicide risk within the general population.

PMID- 19407282
TI  - Immigration and borderline personality disorder.

PMID- 19407283
TI  - Salience dysregulation syndrome: a patient's view.

PMID- 19407284
TI  - Clozapine and risk of pneumonia.

PMID- 19407285
TI  - Dual diagnosis quandries.

PMID- 19407287
TI  - Articular cartilage tissue engineering: today's research, tomorrow's practice?
AB  - Articular cartilage repair remains a challenge to surgeons and basic scientists.
      The field of tissue engineering allows the simultaneous use of material
      scaffolds, cells and signalling molecules to attempt to modulate the regenerative
      tissue. This review summarises the research that has been undertaken to date
      using this approach, with a particular emphasis on those techniques that have
      been introduced into clinical practice, via in vitro and preclinical studies.

PMID- 19407288
TI  - Revision of the cemented femoral stem using a cement-in-cement technique: a five-
      to 15-year review.
AB  - The removal of well-fixed bone cement from the femoral canal during revision of a
      total hip replacement (THR) can be difficult and risks the loss of excessive bone
      stock and perforation or fracture of the femoral shaft. Retaining the cement
      mantle is attractive, yet the technique of cement-in-cement revision is not
      widely practised. We have used this procedure at our hospital since 1989. The
      stems were removed to gain a better exposure for acetabular revision, to alter
      version or leg length, or for component incompatibility. We studied 136 hips in
      134 patients and followed them up for a mean of eight years (5 to 15). A further
      revision was required in 35 hips (25.7%), for acetabular loosening in 26 (19.1%),
      sepsis in four, instability in three, femoral fracture in one and stem fracture
      in one. No femoral stem needed to be re-revised for aseptic loosening. A cement
      in-cement revision of the femoral stem is a reliable technique in the medium
      term. It also reduces the risk of perforation or fracture of the femoral shaft.

PMID- 19407289
TI  - Persisting muscle atrophy two years after replacement of the hip.
AB  - Muscle atrophy has been demonstrated in patients suffering from osteoarthritis of
      the hip, but little is known about muscular recovery after total hip replacement
      (THR). A total of 20 patients with unilateral osteoarthritis of the hip were
      assessed before, six months and two years after THR. The cross-sectional area and
      radiological density of the muscles of the hip, thigh, calf and back were
      measured using CT. We hypothesised that the muscles would not recover fully after
      operation. After two years comparison of the limb with the THR with the healthy
      limb showed that there was such a reduction in the cross-sectional area in
      iliopsoas (7.0%; p = 0.006) and the hip adductors (8.4%, p = 0.003) and in the
      radiological density in gluteus maximus (10.1 Hounsfield units; p < 0.001),
      gluteus medius/minimus (5.6 Hounsfield units; p = 0.011), iliopsoas (3.9
      Hounsfield units; p < 0.001) and the adductors (2.4 Hounsfield units; p = 0.022).
      Thus, there was persistent muscle atrophy in muscles acting about the hip two
      years after THR. We suggest that an earlier operation or a more intensive
      rehabilitation may reverse these changes.

PMID- 19407290
TI  - Prevalence of associated deformities and hip pain in patients with cam-type
      femoroacetabular impingement.
AB  - Femoroacetabular impingement is a cause of hip pain in adults and is potentially
      a precursor of osteoarthritis. Our aim in this study was to determine the
      prevalence of bilateral deformity in patients with symptomatic cam-type
      femoroacetabular impingement as well as the presence of associated acetabular
      abnormalities and hip pain. We included all patients aged 55 years or less seen
      by the senior author for hip pain, with at least one anteroposterior and lateral
      pelvic radiograph available. All patients with dysplasia and/or arthritis were
      excluded. A total of 113 patients with a symptomatic cam-impingement deformity of
      at least one hip was evaluated. There were 82 men and 31 women with a mean age of
      37.9 years (16 to 55). Bilateral cam-type deformity was present in 88 patients
      (77.8%) while only 23 of those (26.1%) had bilateral hip pain. Painful hips had a
      statistically significant higher mean alpha angle than asymptomatic hips (69.9
      degrees vs 63.1 degrees , p < 0.001). Hips with an alpha angle of more than 60
      degrees had an odds ratio of being painful of 2.59 (95% confidence interval 1.32
      to 5.08, p = 0.006) compared with those with an alpha angle of less than 60
      degrees . Of the 201 hips with a cam-impingement deformity 42% (84) also had a
      pincer deformity. Most patients with cam-type femoroacetabular impingement had
      bilateral deformities and there was an associated acetabular deformity in 84 of
      201 patients (42%). This information is important in order to define the natural
      history of these deformities, and to determine treatment.

PMID- 19407291
TI  - Outcome after primary and secondary replacement for subcapital fracture of the
      hip in 10 264 patients.
AB  - Between 1999 and 2005, 10 264 patients who had undergone total hip replacement
      (THR) for subcapital fracture of the hip were compared with 76 520 in whom THR
      had been performed for other reasons. All the cases were identified through the
      Swedish Hip Arthroplasty Register. The THRs performed as primary treatment for
      fracture were also compared with those done after failure of internal fixation.
      After seven years the rate of revision was higher in THR after fracture (4.4% vs
      2.9%). Dislocation and periprosthetic fracture were the most common causes of
      revision. The risk was higher in men than in women. The type of femoral component
      and the surgical approach influenced the risk. After correction for gender, type
      of component and the surgical approach the revision rates were similar in the
      primary and secondary fracture THR groups. Total hip replacement is therefore a
      safe method for both the primary and secondary management of fracture of the hip.

PMID- 19407292
TI  - Intra-articular injection versus portal infiltration of 0.5% bupivacaine
      following arthroscopy of the knee: a prospective, randomised double-blinded
      trial.
AB  - The administration of intra-articular local anaesthetic is common following
      arthroscopy of the knee. However, recent evidence has suggested that bupivacaine
      may be harmful to articular cartilage. This study aimed to establish whether
      infiltration of bupivacaine around the portals is as effective as intra-articular
      injection. We randomised 137 patients to receive either 20 ml 0.5% bupivacaine
      introduced into the joint (group 1) or 20 ml 0.5% bupivacaine infiltrated only
      around the portals (group 2) following arthroscopy. A visual analogue scale was
      administered one hour post-operatively to assess pain relief. Both patients and
      observers were blinded to the treatment group. A power calculation was performed.
      The mean visual analogue score was 3.24 (sd 2.20) in group I and 3.04 (sd 2.31)
      in group 2. This difference was not statistically significant (p = 0.62).
      Infiltration of bupivacaine around the portals had an equivalent effect on pain
      scores at one hour, and we would therefore recommend this technique to avoid the
      possible chondrotoxic effect of intra-articular bupivacaine.

PMID- 19407293
TI  - Premature failure of Kinemax Plus total knee replacements.
AB  - We describe a cohort of patients with a high rate of mid-term failure following
      Kinemax Plus total knee replacement inserted between 1998 and 2001. This implant
      has been recorded as having a survival rate of 96% at ten years. However, in our
      series the survival rate was 75% at nine years. This was also significantly lower
      than that of subsequent consecutive series of PFC Sigma knee replacements
      performed by the same surgeon. No differences were found in the clinical and
      radiological parameters between the two groups. At revision the most striking
      finding was polyethylene wear. An independent analysis of the polyethylene
      components was therefore undertaken. Scanning electron microscopy revealed type 2
      fusion defects in the ultra-high molecular weight polyethylene (UHMWPE), which
      indicated incomplete boundary fusion. Other abnormalities consistent with weak
      UHMWPE particle interface strength were present in both the explanted inserts and
      in unused inserts from the same period. We consider that these type 2 fusion
      defects are the cause of the early failure of the Kinemax implants. This may
      represent a manufacturing defect resulting in a form of programmed polyethylene
      failure.

PMID- 19407294
TI  - Subtalar and talonavicular arthrodesis through a single medial approach for the
      correction of severe planovalgus deformity.
AB  - We describe a retrospective review of the clinical and radiological parameters of
      32 feet in 30 patients (10 men and 20 women) who underwent correction for
      malalignment of the hindfoot with a modified double arthrodesis through a medial
      approach. The mean follow-up was 21 months (13 to 37). Fusion was achieved in all
      feet at a mean of 13 weeks (6 to 30). Apart from the calcaneal pitch angle, all
      angular measurements improved significantly after surgery. Primary wound healing
      occurred without complications. The isolated medial approach to the subtalar and
      talonavicular joints allows good visualisation which facilitated the reduction
      and positioning of the joints. It was also associated with fewer problems with
      wound healing than the standard lateral approach.

PMID- 19407295
TI  - Pronator teres transfer to correct pronation deformity of the forearm after an
      obstetrical brachial plexus injury.
AB  - A pronation deformity of the forearm following an obstetric brachial plexus
      injury causes functional and cosmetic disability. We evaluated the results of
      pronator teres transfer to correct their deformity in 14 children treated over a
      period of four years. The mean age at surgery was 7.6 years (5 to 15). The
      indication for surgery in each case was impairment of active supination in a
      forearm that could be passively supinated provided that there was no medial
      contracture of the shoulder and normal function of the hand. The median follow-up
      was 20.4 months (8 to 42). No patient was lost to follow-up. Qualitative results
      were also assessed. The median active supination improved from 5 degrees (0
      degrees to 10 degrees ) to 75 degrees (70 degrees to 80 degrees ) with no loss of
      pronation. A passively correctible pronation contracture can be corrected safely
      and effectively by the transfer of pronator teres.

PMID- 19407296
TI  - Delayed operative management of fractures of the scapula.
AB  - Between 1998 and 2007, 22 patients with fractures of the scapula had operative
      treatment more than three weeks after injury. The indications for operation
      included displaced intra-articular fractures, medialisation of the glenohumeral
      joint, angular deformity, or displaced double lesions of the superior shoulder
      suspensory complex. Radiological and functional outcomes were obtained for 16 of
      22 patients. Disabilities of the Arm, Shoulder, Hand (DASH) and Short form-36
      scores were collected for 14 patients who were operated on after March 2002. The
      mean delay from injury to surgery was 30 days (21 to 57). The mean follow-up was
      for 27 months (12 to 72). At the last review the mean DASH score was 14 (0 to
      41). Of the 16 patients with follow-up, 13 returned to their previous employment
      and recreational activities without restrictions. No wound complications,
      infection or nonunion occurred. Malunion of the scapula can be prevented by
      surgical treatment of fractures in patients with delayed presentation. Surgery is
      safe, effective, and gives acceptable functional results.

PMID- 19407297
TI  - Percutaneous fusion of the sacroiliac joint with hollow modular anchorage screws:
      clinical and radiological outcome.
AB  - We reviewed 15 consecutive patients, 11 women and four men, with a mean age of
      48.7 years (37.3 to 62.6), who between July 2004 and August 2007 had undergone
      percutaneous sacroiliac fusion using hollow modular anchorage screws filled with
      demineralised bone matrix. Each patient was carefully assessed to exclude other
      conditions and underwent pre-operative CT and MR scans. The diagnosis of
      symptomatic sacroiliac disease was confirmed by an injection of local anaesthetic
      and steroid under image intensifier control. The short form-36 questionnaire and
      Majeed's scoring system were used for pre- and post-operative functional
      evaluation. Post-operative radiological evaluation was performed using plain
      radiographs. Intra-operative blood loss was minimal and there were no post
      operative clinical or radiological complications. The mean follow-up was for 17
      months (9 to 39). The mean short form-36 scores improved from 37 (23 to 51) to 80
      (67 to 92) for physical function and from 53 (34 to 73) to 86 (70 to 98) for
      general health (p = 0.037). The mean Majeed's score improved from 37 (18 to 54)
      pre-operatively to 79 (63 to 96) post-operatively (p = 0.014). There were 13 good
      to excellent results. The remaining two patients improved in short form-36 from a
      mean of 29 (26 to 35) to 48 (44 to 52). Their persistent pain was probably due to
      concurrent lumbar pathology. We conclude that percutaneous hollow modular
      anchorage screws are a satisfactory method of achieving sacroiliac fusion.

PMID- 19407298
TI  - Management and outcome of 103 acute fractures of the coronoid process of the
      ulna.
AB  - A series of 103 acute fractures of the coronoid process of the ulna in 101
      patients was reviewed to determine their frequency. The Regan-Morrey
      classification, treatment, associated injuries, course and outcomes were
      evaluated. Of the 103 fractures, 34 were type IA, 17 type IB, ten type IIA, 19
      type IIB, ten type IIIA and 13 type IIIB. A total of 44 type-I fractures (86%)
      were treated conservatively, while 22 type-II (76%) and all type-III fractures
      were managed by operation. At follow-up at a mean of 3.4 years (1 to 8.9) the
      range of movement differed significantly between the types of fracture (p =
      0.002). Patients with associated injuries had a lower Mayo elbow performance
      score (p = 0.03), less extension (p = 0.03), more pain (p = 0.007) and less
      pronosupination (p = 0.004), than those without associated injuries. The presence
      of a fracture of the radial head had the greatest effect on outcome. An
      improvement in outcome relative to that of a previous series was noted, perhaps
      because of more aggressive management and early mobilisation. While not providing
      complete information about the true details of a fracture and its nature, the
      Regan-Morrey classification is useful as a broad index of severity and prognosis.

PMID- 19407299
TI  - Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after
      elective hip and knee replacement.
AB  - A once-daily dose of rivaroxaban 10 mg, an oral, direct Factor Xa inhibitor, was
      compared with enoxaparin 40 mg subcutaneously once daily for prevention of venous
      thromboembolism in three studies of patients undergoing elective hip and knee
      replacement (RECORD programme). A pooled analysis of data from these studies (n =
      9581) showed that rivaroxaban was more effective than enoxaparin in reducing the
      incidence of the composite of symptomatic venous thromboembolism and all-cause
      mortality at two weeks (0.4% vs 0.8%, respectively, odds ratio 0.44; 95%
      confidence interval 0.23 to 0.79; p = 0.005), and at the end of the planned
      medication period (0.5% vs 1.3%, respectively; odds ratio 0.38; 95% confidence
      interval 0.22 to 0.62; p < 0.001). The rate of major bleeding was similar at two
      weeks (0.2% for both) and at the end of the planned medication period (0.3% vs
      0.2%). Rivaroxaban started six to eight hours after surgery was more effective
      than enoxaparin started the previous evening in preventing symptomatic venous
      thromboembolism and all-cause mortality, without increasing major bleeding.

PMID- 19407300
TI  - The incidence of fatal pulmonary embolism after primary hip and knee replacement
      in a consecutive series of 4253 patients.
AB  - We studied 4253 patients undergoing primary joint replacement between November
      2002 and November 2007, of whom 4060 received aspirin only as chemical
      prophylaxis; 46 were mistakenly given low molecular weight heparin initially,
      which was stopped and changed to aspirin; 136 received no chemoprophylaxis and 11
      patients received warfarin because of a previous history of pulmonary embolism.
      We identified the rate of clinical thromboembolism before and after discharge,
      and the mortality from pulmonary embolism at 90 days. The overall death rate was
      0.31% (13 of 4253) and the rate of fatal pulmonary embolism was 0.07% (3 of
      4253). Our data suggest that fatal pulmonary embolism is not common following
      elective primary joint replacement, and with modern surgical practice elective
      hip and knee replacement should no longer be considered high-risk procedures.

PMID- 19407301
TI  - Nerve reconstruction in patients with obstetric brachial plexus injury results in
      worsening of glenohumeral deformity: a case-control study of 75 patients.
AB  - Whereas a general trend in the management of obstetric brachial plexus injuries
      has been nerve reconstruction in patients without spontaneous recovery of biceps
      function by three to six months of age, many recent studies suggest this may be
      unnecessary. In this study, the severity of glenohumeral dysplasia and shoulder
      function and strength in two groups of matched patients with a C5-6 lesion at a
      mean age of seven years (2.7 to 13.3) were investigated. One group (23 patients)
      underwent nerve reconstruction and secondary operations, and the other (52
      patients) underwent only secondary operations for similar initial clinical
      presentations. In the patients with nerve reconstruction shoulder function did
      not improve and they developed more severe shoulder deformities (posterior
      subluxation, glenoid version and scapular elevation) and required a mean of 2.4
      times as many operations as patients without nerve reconstruction. This study
      suggests that less invasive management, addressing the muscle and bone
      complications, is a more effective approach. Nerve reconstruction should be
      reserved for those less common cases where the C5 and C6 nerve roots will not
      recover.

PMID- 19407302
TI  - Neonatal foot deformities and their relationship to developmental dysplasia of
      the hip: an 11-year prospective, longitudinal observational study.
AB  - In a prospective study over 11 years we assessed the relationship between
      neonatal deformities of the foot and the presence of ultrasonographic
      developmental dysplasia of the hip (DDH). Between 1 January 1996 and 31 December
      2006, 614 infants with deformities of the foot were referred for clinical and
      ultrasonographic evaluation. There were 436 cases of postural talipes equinovarus
      deformity (TEV), 60 of fixed congenital talipes equinovarus (CTEV), 93 of
      congenital talipes calcaneovalgus (CTCV) and 25 of metatarsus adductus. The
      overall risk of ultrasonographic dysplasia or instability was 1:27 in postural
      TEV, 1:8.6 in CTEV, 1:5.2 in CTCV and 1:25 in metatarsus adductus. The risk of
      type-IV instability of the hip or irreducible dislocation was 1:436 (0.2%) in
      postural TEV, 1:15.4 (6.5%) in CTCV and 1:25 (4%) in metatarsus adductus. There
      were no cases of hip instability (type IV) or of irreducible dislocation in the
      CTEV group. Routine screening for DDH in cases of postural TEV and CTEV is no
      longer advocated. The former is poorly defined, leading to the over-diagnosis of
      a possibly spurious condition. Ultrasonographic imaging and surveillance of hips
      in infants with CTCV and possibly those with metatarsus adductus should continue.

PMID- 19407303
TI  - The use of ultrasound-guided wire localisation in orthopaedics.
AB  - The use of ultrasound-guided wire localisation of lesions is not well described
      in the orthopaedic literature. We describe a case of an impalpable schwannoma of
      the femoral nerve and another of sacroiliitis with an associated pelvic abscess.
      In both, surgical localisation was difficult. Peri-operative ultrasound-guided
      wire localisation was used to guide surgery and minimise tissue damage, thereby
      optimising the results and recovery of the patient.

PMID- 19407304
TI  - Calcaneogenesis.
AB  - We report a case in which Ilizarov distraction osteogenesis was used to lengthen
      the portion of calcaneum that remained after a radical debridement for
      osteomyelitis. The patient was able to walk normally in unmodified shoes at the
      end of his treatment.

PMID- 19407305
TI  - Slipped upper femoral epiphysis in Hashimoto's thyroiditis in a 29-year-old man.
AB  - Slipped upper femoral epiphysis (SUFE) with an open physis is rare in an adult
      and the condition may present without prior diagnosis of an underlying medical
      condition. We have treated a 29-year-old man with bilateral SUFE associated with
      autoimmune hypothyroidism. The management was delayed and complicated by co
      existing autoimmune chronic active hepatitis. He underwent thyroxine therapy and
      bilateral pinning in situ with a single ASNIS screw. Closure of the physis
      occurred after five months on the right side. The left side required a further
      corrective intertrochanteric osteotomy, and it was only after 13 months that
      complete fusion of this physis was seen. The case highlights the need to consider
      endocrine and metabolic conditions in atypical presentation of SUFE.

PMID- 19407306
TI  - Experimental results of combining bisphosphonates with allograft in a rat model.
AB  - Soaking bone grafts in a bisphosphonate solution before implantation can prevent
      their resorption and increase the local bone density in rats and humans. However,
      recent studies suggest that pre-treatment of allografts with bisphosphonate can
      prevent bone ingrowth into impaction grafts. We tested the hypothesis that
      excessive amounts of bisphosphonate would also cause a negative response in less
      dense grafts. We used a model where non-impacted metaphyseal bone grafts were
      randomised into three groups with either no bisphosphonate, alendronate followed
      by rinsing, and alendronate without subsequent rinsing, and inserted into bone
      chambers in rats. The specimens were evaluated histologically at one week, and by
      histomorphometry and radiology at four weeks. At four weeks, both bisphosphonate
      groups showed an increase in the total bone content, increased newly formed bone,
      and higher radiodensity than the controls. In spite of being implanted in a
      chamber with a limited opportunity to diffuse, even an excessive amount of
      bisphosphonate improved the outcome. We suggest that the negative results seen by
      others could be due to the combination of densely compacted bone and a
      bisphosphonate. We suggest that bisphosphonates are likely to have a negative
      influence where resorption is a prerequisite to create space for new bone
      ingrowth.

PMID- 19407307
TI  - An in vitro study of the strain distribution in human femora with anatomical and
      customised femoral stems.
AB  - Hydroxyapatite-coated standard anatomical and customised femoral stems are
      designed to transmit load to the metaphyseal part of the proximal femur in order
      to avoid stress shielding and to reduce resorption of bone. In a randomised in
      vitro study, we compared the changes in the pattern of cortical strain after the
      insertion of hydroxyapatite-coated standard anatomical and customised stems in 12
      pairs of human cadaver femora. A hip simulator reproduced the physiological loads
      on the proximal femur in single-leg stance and stair-climbing. The cortical
      strains were measured before and after the insertion of the stems. Significantly
      higher strain shielding was seen in Gruen zones 7, 6, 5, 3 and 2 after the
      insertion of the anatomical stem compared with the customised stem. For the
      anatomical stem, the hoop strains on the femur also indicated that the load was
      transferred to the cortical bone at the lower metaphyseal or upper diaphyseal
      part of the proximal femur. The customised stem induced a strain pattern more
      similar to that of the intact femur than the standard, anatomical stem.

PMID- 19407308
TI  - A common reference frame for describing rotation of the distal femur: a ct-based
      kinematic study using cadavers.
AB  - The understanding of rotational alignment of the distal femur is essential in
      total knee replacement to ensure that there is correct placement of the femoral
      component. Many reference axes have been described, but there is still
      disagreement about their value and mutual angular relationship. Our aim was to
      validate a geometrically-defined reference axis against which the surface-derived
      axes could be compared in the axial plane. A total of 12 cadaver specimens
      underwent CT after rigid fixation of optical tracking devices to the femur and
      the tibia. Three-dimensional reconstructions were made to determine the
      anatomical surface points and geometrical references. The spatial relationships
      between the femur and tibia in full extension and in 90 degrees of flexion were
      examined by an optical infrared tracking system. After co-ordinate transformation
      of the described anatomical points and geometrical references, the projection of
      the relevant axes in the axial plane of the femur were mathematically achieved.
      Inter- and intra-observer variability in the three-dimensional CT reconstructions
      revealed angular errors ranging from 0.16 degrees to 1.15 degrees for all axes
      except for the trochlear axis which had an interobserver error of 2 degrees .
      With the knees in full extension, the femoral transverse axis, connecting the
      centres of the best matching spheres of the femoral condyles, almost coincided
      with the tibial transverse axis (mean difference -0.8 degrees , sd 2.05). At 90
      degrees of flexion, this femoral transverse axis was orthogonal to the tibial
      mechanical axis (mean difference -0.77 degrees , sd 4.08). Of all the surface
      derived axes, the surgical transepicondylar axis had the closest relationship to
      the femoral transverse axis after projection on to the axial plane of the femur
      (mean difference 0.21 degrees , sd 1.77). The posterior condylar line was the
      most consistent axis (range -2.96 degrees to -0.28 degrees , sd 0.77) and the
      trochlear anteroposterior axis the least consistent axis (range -10.62 degrees to
      +11.67 degrees , sd 6.12). The orientation of both the posterior condylar line
      and the trochlear anteroposterior axis (p = 0.001) showed a trend towards
      internal rotation with valgus coronal alignment.

PMID- 19407309
TI  - Chondrocyte survival in articular cartilage: the influence of subchondral bone in
      a bovine model.
AB  - The aim of this study was to determine whether subchondral bone influences in
      situ chondrocyte survival. Bovine explants were cultured in serum-free media over
      seven days with subchondral bone excised from articular cartilage (group A),
      subchondral bone left attached to articular cartilage (group B), and subchondral
      bone excised but co-cultured with articular cartilage (group C). Using confocal
      laser scanning microscopy, fluorescent probes and biochemical assays, in situ
      chondrocyte viability and relevant biophysical parameters (cartilage thickness,
      cell density, culture medium composition) were quantified over time (2.5 hours vs
      seven days). There was a significant increase in chondrocyte death over seven
      days, primarily within the superficial zone, for group A, but not for groups B or
      C (p < 0.05). There was no significant difference in cartilage thickness or cell
      density between groups A, B and C (p > 0.05). Increases in the protein content of
      the culture media for groups B and C, but not for group A, suggested that the
      release of soluble factors from subchondral bone may have influenced chondrocyte
      survival. In conclusion, subchondral bone significantly influenced chondrocyte
      survival in articular cartilage during explant culture. The extrapolation of bone
      cartilage interactions in vitro to the clinical situation must be made with
      caution, but the findings from these experiments suggest that future
      investigation into in vivo mechanisms of articular cartilage survival and
      degradation must consider the interactions of cartilage with subchondral bone.

PMID- 19407312
TI  - Simultaneous anterior decompression and posterior instrumentation of the
      tuberculous spine using an anterolateral extrapleural approach.

PMID- 19407313
TI  - Close to unraveling the secrets of congenital dyserythropoietic anemia types I
      and II.
AB  - The congenital dyserythropoietic anemias are rare recessive disorders
      characterized by erythroblast multinuclearity, ineffective erythropoiesis, anemia
      and iron overload. In this perspective article, Drs. Iolascon and Delaunay
      examine genetic and clinical aspects of these inherited disorders.

PMID- 19407314
TI  - Clinical relevance of extra-hematologic comorbidity in the management of patients
      with myelodysplastic syndrome.
AB  - Myelodysplastic syndromes occur mainly in older persons, and these patients are
      likely to have comorbidities that significantly worsen their survival. In this
      perspective article, Drs. Della Porta and Malcovati examine the relevance of
      comorbidities for clinical decision making in patients with myelodysplasti
      syndromes.

PMID- 19407315
TI  - The molecular basis of familial chronic lymphocytic leukemia.
AB  - Our understanding of the genetic basis of chronic lymphocytic leukemia is only
      just starting to be recognized. This perspective article by Drs. Crowther
      Swanepoel and Houlston provides an up-to-date review the molecular epidemiology
      of chronic lymphocytic leukemia, with emphasis on the integration of biology and
      genomics.

PMID- 19407316
TI  - Clinical and laboratory versus molecular markers for a correct classification of
      von Willebrand disease.
AB  - von Willebrand disease (VWD) is the most common inherited bleeding disorder. In
      this perspective article, Drs. Federici and Canciani review how correlating the
      clinical, laboratory and genetic features of von Willebrand disease has led to
      improved understanding of its pathophysiology. They show how this has
      rationalized classification, which in turn can be used to improve treatment of
      these patients.

PMID- 19407317
TI  - Factor IX and deep vein thrombosis.
AB  - Elevated levels of several coagulation factors have been found to be associated
      with an increased risk of thrombosis. In this perspective article, Dr. Lowe
      examines the implications of the report by Bezemer and coworkers in this issue
      for our understanding of the mechanisms involved and how they should direct
      future research.

PMID- 19407318
TI  - Inhibitors of poly ADP-ribose polymerase (PARP) induce apoptosis of myeloid
      leukemic cells: potential for therapy of myeloid leukemia and myelodysplastic
      syndromes.
AB  - Background Aberrant or impaired repair of double-strand DNA breaks is a common
      feature of de novo acute myeloid leukemia and myelodysplastic syndromes. Since
      poly (ADP-ribose) polymerase (PARP) inhibitors have been recently shown to
      selectively target cells with defects in double-strand DNA repair, the aim of
      this study was to explore the possibility of exploiting defects in DNA repair in
      leukemic cells using PARP inhibitors. DESIGN AND METHODS: Leukemic cell lines
      were exposed to various PARP inhibitors alone and in combination with non
      cytotoxic concentrations of DNA methyltransferase inhibitor, 5' aza-2'
      deoxycytidine and/or the histone deacetylase inhibitor, MS275, to test for
      potentiation of apoptosis with these agents. RESULTS: PARP inhibitors, KU-0058948
      and PJ34, induced cell cycle arrest and apoptosis of primary myeloid leukemic
      cells and myeloid leukemic cell lines in vitro. Immunofluorescence analysis also
      revealed that PARP inhibitor sensitivity in these leukemic cells was due to a
      defect in homologous recombination DNA repair. Addition of 5' aza-2'
      deoxycytidine failed to increase the cytotoxicity of PARP inhibitors. In
      contrast, MS275 potentiated the cytotoxic effect of KU-0058948 and PJ34 in all
      PARP inhibitor-sensitive leukemic cells. Immunofluorescence analysis supported
      the idea that histone deacetylase inhibitors potentiate cytotoxicity by
      inhibiting DNA repair processes. Conclusions On the basis of the data presented
      here, we suggest that PARP inhibitors can potentially exploit defects in double
      strand DNA break repair in leukemic cells, paving the way for testing the
      therapeutic potential of these agents in myelodysplastic syndromes and acute
      myeloid leukemia.

PMID- 19407319
TI  - Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in
      patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid
      administration.
AB  - Dickkopf-1 is an inhibitor of Wnt signaling, which is crucial for osteoblast
      differentiation. We evaluated serum levels of Dickkopf-1 in 66 patients with
      thalassemia-induced osteoporosis who received therapy with zoledronic acid in a
      placebo-controlled, randomized trial. At baseline, thalassemia patients had
      increased serum levels of Dickkopf-1 that correlated with reduced bone mineral
      density of the lumbar spine and the distal radius. High Dickkopf-1 also
      correlated with increased bone resorption and reduced bone formation markers.
      Zoledronic acid produced a reduction in serum Dickkopf-1, which was associated
      with bone mineral density increase after 12 months of therapy. On the contrary,
      placebo group showed a borderline increase of Dickkopf-1, which was higher in
      patients who showed deterioration in pain scores. These results suggest that
      Dickkopf-1 is implicated in the pathogenesis of osteoporosis in thalassemia and
      reveal Dickkopf-1 as a possible target for the development of novel agents for
      the management of thalassemia-induced osteoporosis.

PMID- 19407320
TI  - Sustained durability of responses and improved progression-free and overall
      survival with imatinib treatment for accelerated phase and blast crisis chronic
      myeloid leukemia: long-term follow-up of the STI571 0102 and 0109 trials.

PMID- 19407321
TI  - The development and validation of the Age-Based Rejection Sensitivity
      Questionnaire.
AB  - PURPOSE: There is much evidence suggesting that older adults are often negatively
      affected by aging stereotypes; however, no method to identify individual
      differences in vulnerability to these effects has yet been developed. The purpose
      of this study was to develop a reliable and valid questionnaire to measure
      individual differences in the tendency to anxiously expect, readily perceive, and
      intensely react to age-based rejection among older adults: the Age-Based
      Rejection Sensitivity Questionnaire (RSQ-Age). DESIGN AND METHODS: A pilot sample
      of older adults was asked to identify situations in which negative outcomes
      related to being an older adult might occur. From these responses, 58 scenarios
      representing 8 domains and themes were identified. Thirty initial items were
      created from this pool of scenarios, and this 30-item RSQ-Age underwent intensive
      testing and refinement to create the final 15-item RSQ-Age. The 15-item RSQ-Age
      was assessed for internal and test-retest reliability, as well as construct
      validity. RESULTS: Results revealed that the RSQ-Age has good internal (alpha =
      .91) and test-retest, r(72) = .74, p < .01, reliability and is a valid measure of
      age-based rejection sensitivity (RS). Construct validity was supported by
      correlations with personal RS, age-based stigma consciousness, self
      consciousness, awareness of ageism, and self-esteem. IMPLICATIONS: The RSQ-Age is
      a useful measure for researchers and health care workers interested in the
      relationships between expectancy, perceptions, and reactions to age-based stigma
      and subsequent cognitive, behavioral, and health-related consequences.

PMID- 19407322
TI  - Hunting for the function of Huntingtin.

PMID- 19407323
TI  - This revolution will be digitized: online tools for radical collaboration.

PMID- 19407324
TI  - Rats!

PMID- 19407325
TI  - Unique training brings young scientists up to speed in translational research.

PMID- 19407326
TI  - Creative approaches in public science education.

PMID- 19407328
TI  - Using zebrafish to understand the genome: an interview with Nancy Hopkins.
      [Interview by Kristin Kain].

PMID- 19407329
TI  - Development of animal models for the acute respiratory distress syndrome.
AB  - Injury to the lung parenchyma results in the acute respiratory distress syndrome
      (ARDS), which is a common and life-threatening cause of respiratory failure and
      mortality that develops after a variety of insults, including sepsis, multiple
      trauma, pneumonia, aspiration of gastric contents and severe burns. The
      pathogenesis of ARDS is complex with loss of the alveolar-capillary barrier and
      flooding of the airspaces with protein-rich fluid; injury to the alveolar
      epithelium; an influx of neutrophils and macrophages; and fibrin deposition as a
      result of activation of coagulation and inhibition of fibrinolysis. These changes
      develop over hours to a few days after the initiating event and often take days
      or weeks to resolve. Despite decades of research, there is only one therapy (low
      tidal volume ventilation) that has been shown to reduce mortality in ARDS.
      Further research into the pathogenesis of this devastating condition is crucial
      for the development of novel and specific therapies that target specific disease
      mechanisms. Unfortunately, no single animal model of ARDS replicates the complex
      pathophysiological changes seen in patients. This is a severe limitation in the
      study of ARDS and has impaired scientific and therapeutic progress in this field.
      Here, we discuss the primary features of this syndrome, highlight limitations of
      current animal models and suggest new approaches to investigate key components of
      pathogenesis. Hopefully, as new technologies and approaches emerge, barriers to
      scientific progress in ARDS will be overcome.

PMID- 19407330
TI  - Caenorhabditis elegans as an emerging model for studying the basic biology of
      obesity.
AB  - The health problem of obesity and its related disorders highlights the need for
      understanding the components and pathways that regulate lipid metabolism. Because
      energy balance is maintained by a complex regulatory network, the use of a
      powerful genetic model like C. elegans can complement studies on mammalian
      physiology by offering new opportunities to identify genes and dissect
      complicated regulatory circuits. Many of the components that are central to
      governing human metabolism are conserved in the worm. Although the study of lipid
      metabolism in C. elegans is still relatively young, much progress has already
      been made in tracing out genetic pathways that regulate fat storage and in
      developing assays to explore different aspects of metabolic regulation and food
      sensation. This model system holds great promise for helping tease apart the
      complicated network of genes that maintain a proper energy balance.

PMID- 19407331
TI  - A comprehensive definition for metabolic syndrome.
AB  - The metabolic syndrome refers to the co-occurrence of several known
      cardiovascular risk factors, including insulin resistance, obesity, atherogenic
      dyslipidemia and hypertension. These conditions are interrelated and share
      underlying mediators, mechanisms and pathways. There has been recent controversy
      about its definition and its utility. In this article, I review the current
      definitions for the metabolic syndrome and why the concept is important. It
      identifies a subgroup of patients with shared pathophysiology who are at high
      risk of developing cardiovascular disease and type 2 diabetes. By considering the
      central features of the metabolic syndrome and how they are related, we may
      better understand the underlying pathophysiology and disease pathogenesis. A
      comprehensive definition for the metabolic syndrome and its key features would
      facilitate research into its causes and hopefully lead to new insights into
      pharmacologic and lifestyle treatment approaches.

PMID- 19407333
TI  - Community-based peer-led diabetes self-management: a randomized trial.
AB  - PURPOSE: The purpose of this study is to determine the effectiveness of a
      community-based diabetes self-management program comparing treatment participants
      to a randomized usual-care control group at 6 months. METHODS: A total of 345
      adults with type 2 diabetes but no criteria for high A1C were randomized to a
      usual-care control group or 6-week community-based, peer-led diabetes self
      management program (DSMP). Randomized participants were compared at 6 months. The
      DSMP intervention participants were followed for an additional 6 months (12
      months total). A1C and body mass index were measured at baseline, 6 months, and
      12 months. All other data were collected by self-administered questionnaires.
      RESULTS: At 6 months, DSMP participants did not demonstrate improvements in A1C
      as compared with controls. Baseline A1C was much lower than in similar trials.
      Participants did have significant improvements in depression, symptoms of
      hypoglycemia, communication with physicians, healthy eating, and reading food
      labels (P < .01). They also had significant improvements in patient activation
      and self-efficacy. At 12 months, DSMP intervention participants continued to
      demonstrate improvements in depression, communication with physicians, healthy
      eating, patient activation, and self-efficacy (P < .01). There were no
      significant changes in utilization measures. CONCLUSIONS: These findings suggest
      that people with diabetes without elevated A1C can benefit from a community
      based, peer-led diabetes program. Given the large number of people with diabetes
      and lack of low-cost diabetes education, the DSMP deserves consideration for
      implementation.

PMID- 19407335
TI  - E-mail Use among a sample of intimate partner violence shelter residents.
AB  - Although it is estimated that approximately 75% of U.S. adults have e-mail
      access, the proportion of battered women's shelter residents who use e-mail is
      currently unknown. Remaining in contact with residents following shelter stays is
      challenging. E-mail might hold promise for follow-up contact if a sufficient
      number of survivors use e-mail and safety concerns can be addressed. Among a
      convenience sample of residents of 11 Massachusetts shelters (N = 57), the
      authors find that 47% had a current e-mail account. Among those with e-mail
      accounts, 89% used e-mail in locations other than their own homes; 81% reported
      that, to their knowledge, their e-mail accounts had never been accessed by
      unauthorized dating partners; and 88% reported that they thought it would be safe
      for the shelter to e-mail them following their departure. Additional research
      assessing the feasibility (i.e., safety, acceptability, and cost benefit) of
      remaining in contact with shelter residents via the Internet would be beneficial.

PMID- 19407332
TI  - Reverse translational strategies for developing animal models of bipolar
      disorder.
AB  - Bipolar disorder (BD) affects a significant portion of the population of the
      world, yet there has been limited success in developing novel treatments for the
      disorder. One of the major reasons for this dearth is the absence of suitable
      animal models for BD. Traditionally, animal models of human phenomena have been
      evaluated based on similarity to the human syndrome, response to appropriately
      corresponding medications, and the degree to which a model supports a common
      mechanistic theory between the human disorder and the model itself. The following
      review emphasizes the use of 'reverse translation', drawing on patient-based
      findings to develop suitable animal models for BD. We highlight some examples of
      this strategy, emphasizing their construct validity as a starting point. These
      studies have produced informative models that have altered the expression of
      genes/pathways implicated in BD, including the point mutation D181A of mouse
      mitochondrial DNA polymerase (POLG), glutamate receptor 6 (GluR6), Clock,
      extracellular regulated kinase 1 (ERK1), glycogen synthase kinase-3beta (GSK
      3beta), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated athanogene (BAG-1). These
      studies demonstrate that this method is useful, viable and deserves attention in
      new efforts to generate animal models of BD.

PMID- 19407336
TI  - Structure-activity relationships and human relevance for perfluoroalkyl acid
      induced transcriptional activation of peroxisome proliferation in liver cell
      cultures.
AB  - Perfluoroalkyl acids (PFAAs) are widely distributed and environmentally
      persistent agents whose potential toxicity is not yet fully characterized.
      Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid elicit a number
      of potential toxicities in rodents, the most prevalent of which are governed by
      activation of the peroxisome proliferator-activated receptor alpha (PPARalpha).
      The purpose of this investigation was twofold: (1) To conduct a structure
      activity relationship study of the transcriptional activation of peroxisome
      proliferation in primary rat liver cell cultures for PFAA-related carboxylic and
      sulfonic acids of varying carbon chain length and (2) to explore whether this
      activity can be translated to human liver cells in culture. Exposure to PFOA
      caused a dose-dependent stimulation of the expression of acyl-CoA oxidase (Acox),
      Cte/Acot1, and Cyp4a1/11 transcripts that are indicative of peroxisome
      proliferation in primary rat hepatocytes. PFOA concentrations of 30 microM and
      above caused cell injury characterized by the expression of Ddit3.
      Perfluorobutanoic acid (PFBA), on the other hand, stimulated Acox, Cte/Acot1, and
      Cyp4a1/11 gene expression in primary rat hepatocytes only at concentrations of
      100 microM and above. Neither PFOA nor PFBA at concentrations up to 200 microM
      stimulated PPARalpha-related gene expression in either primary or HepG2 human
      liver cells. These data demonstrate that (1) PFFAs cause a concentration- and
      chain length-dependent increase in expression of gene targets related to cell
      injury and PPARalpha activation in primary rat hepatocytes, (2) the sulfonates
      are less potent than the corresponding carboxylates in stimulating PPARalpha
      related gene expression in rat hepatocytes, and (3) stimulation of PPARalpha
      mediated gene transcription is a mechanism that is not shared by human liver
      cells, adding further substantiation that PPARalpha-dependent liver toxicity in
      rodents does not extrapolate to assessing human health concerns.

PMID- 19407337
TI  - Compensatory induction of liver efflux transporters in response to ANIT-induced
      liver injury is impaired in FXR-null mice.
AB  - Alpha-naphthyl isothiocyanate (ANIT) is a hepatotoxicant that produces acute
      intrahepatic cholestasis in rodents. Farnesoid X receptor (FXR) and pregnane X
      receptor (PXR) are two major bile acid sensors in liver. The purpose of this
      study was to characterize the regulation of hepatic transporters by FXR and PXR
      during ANIT-induced liver injury. Wild-type, FXR-null, and PXR-null mice were
      administered ANIT (75 mg/kg, po) and evaluated 48 h later for hepatotoxicity and
      messenger RNA (mRNA) expression of basolateral uptake (sodium taurocholate
      cotransporting polypeptide, organic anion transporting polypeptide [Oatp] 1a1,
      Oatp1a4, Oatp1b2) and efflux transporters (organic solute transporter [Ost]
      alpha, Ostbeta, multidrug resistance-associated protein [Mrp] 3, Mrp4), as well
      as canalicular transporters (bile salt export pump [Bsep], Mrp2, multidrug
      resistance protein 2 [Mdr2], ATPase, class I, type 8B, member 1 [Atp8b1]). Livers
      from wild-type and PXR-null mice had comparable multifocal necrosis 48 h after
      ANIT. However, ANIT-treated FXR-null mice have fewer and smaller necrotic foci
      than wild-type mice but had scattered single-cell hepatocyte necrosis throughout
      the liver. Serum alanine transaminase, alkaline phosphatase (ALP), and direct
      bilirubin were increased in all genotypes, with higher ALP levels in FXR-null
      mice. Serum and liver unconjugated bile acids were higher in ANIT-treated FXR
      null mice than the other two genotypes. ANIT induced mRNA expression of Mdr2,
      Bsep, and Atp8b1 in wild-type and PXR-null mice but failed to upregulate these
      genes in FXR-null mice. mRNA expression of uptake transporters declined in livers
      of all genotypes following ANIT treatment. ANIT increased Ostbeta and Mrp3 mRNA
      in livers of wild-type and PXR-null mice but did not alter Ostbeta mRNA in FXR
      null mice. In conclusion, FXR deficiency enhances susceptibility of mice to ANIT
      induced liver injury, likely a result of impaired induction of hepatobiliary
      efflux transporters and subsequent hepatic accumulation of unconjugated bile
      acids.

PMID- 19407338
TI  - Continuous electrocardiogram reveals differences in the short-term cardiotoxic
      response of Wistar-Kyoto and spontaneously hypertensive rats to doxorubicin.
AB  - Electrocardiography (ECG) is one of the standard technologies used to monitor and
      assess cardiac function, and provide insight into the mechanisms driving
      myocardial pathology. Increased understanding of the effects of cardiovascular
      disease on rat ECG may help make ECG assessments in rat toxicology studies
      routine, thus facilitating continuous measurement of functional decrements
      associated with cardiotoxicant exposure. These studies seek to test the
      hypothesis that hypertensive rats are more susceptible to the short-term
      cardiotoxic effects of doxorubicin (DOX) when compared with normotensive rats
      with respect to continuously measured ECG endpoints. Male Wistar-Kyoto (WKY) and
      spontaneously hypertensive (SH) rats surgically implanted with radiotelemeters
      were treated once a week for three weeks with either vehicle, 1.25 (low), 2.5
      (medium), or 5 (high) mg/kg DOX (i.p.). ECG, heart rate (HR), and core body
      temperature (T(co)) were continuously monitored during the 1-week baseline and
      throughout the experimental period until rats were sacrificed 24 h after the
      third injection. DOX prevented normal body weight gain in both strains and
      significantly decreased diurnal HR and T(co) of high DOX SH rats. In the ECG, SH
      rats had prolonged baseline PR intervals and QT(c) when compared with WKY rats.
      All DOX-treated WKY rats subsequently developed PR interval prolongation; however
      only those treated with high DOX had increased QT(c). DOX caused an increase in
      ST interval in SH rats, and resulted in ECG morphology changes. The number of
      arrhythmias due to DOX was increased in both strains. In conclusion, ECG analysis
      can reveal underlying cardiovascular disease as a risk factor in the heart's
      response to toxicant-induced injury in the rat; and be a valuable tool to
      evaluate baseline vulnerability and assess cardiotoxicity.

PMID- 19407339
TI  - Characterization of a canola C2 domain gene that interacts with PG, an effector
      of the necrotrophic fungus Sclerotinia sclerotiorum.
AB  - Sspg1d, one of endopolygalacturonases, is an important fungal effector secreted
      by the necrotrophic fungus Sclerotinia sclerotiorum during early infection. Using
      sspg1d as bait, a small C2 domain protein (designated as IPG-1) was identified by
      yeast two-hybrid screening of a canola cDNA library. Deletion analysis confirmed
      that the C-terminus of IPG-1 is responsible for its interaction with sspg1d in
      the yeast two-hybrid assay. The sspg1d/IPG-1 interaction was further confirmed in
      plant cells by a biomolecular fluorescence complementation (BiFC) assay. A
      transient expression assay showed that the IPG-1-GFP fusion protein was targeted
      to the plasma membrane and nucleus in onion epidermal cells. Following treatment
      with a Ca(2+) ionophore, it was distributed throughout the cytosol. Real-time PCR
      assay demonstrated that IPG-1 was highly induced by Sclerotinia sclerotiorum in
      canola leaves and stems. Southern blot analysis indicated the presence of about
      five homologues of IPG-1 in the canola genome. Two additional members of the IPG
      1gene family were isolated by RT-PCR. Their sequence similarity with IPG-1 is as
      high as 95%. However, they did not interact with sspg1d in the yeast two-hybrid
      assay. Possible roles of IPG-1 and its association with sspg1d in the defence
      signalling pathway were discussed.

PMID- 19407340
TI  - Enhanced endothelial cell senescence by lithium-induced matrix metalloproteinase
      1 expression.
AB  - Endothelial cell (EC) senescence and dysfunction occurring after chronic injury
      and inflammation are highly associated with the development and progression of
      cardiovascular diseases. However, the factors involved in the establishment of EC
      senescence remain poorly understood. We have previously shown that lithium, an
      inhibitor of glycogen synthase kinase (GSK)-3beta and activator of the Wnt/beta
      catenin signaling pathway, induces an EC senescent-like phenotype. Herein, we
      show that lithium induces a rapid and pronounced up-regulation of the matrix
      metalloproteinase (MMP)-1, an inflammation and senescent cell marker, at the mRNA
      and protein levels, whereas the induction of two other senescent cell markers is
      either weak (interleukin-8) or delayed (plasminogen activator inhibitor-1).
      Lithium effect on MMP-1 expression is also specific among other MMPs and not
      mediated by GSK3beta inhibition. Lithium affects MMP-1 expression mainly at the
      transcriptional level but neither the AP1/Ets regulatory sites nor the redox
      sensitive (-1607/2G) site in MMP-1 promoter are involved in lithium-dependent MMP
      1 regulation. However, down-regulation of p53, a target of lithium in EC, dampens
      both basal and lithium-induced MMP-1 expression, which further links MMP-1 up
      regulation with the establishment of cell senescence. Although increased MMP-1
      levels are usually associated with angiogenesis in enabled proliferative EC, the
      exogenous addition of activated MMP-1 on lithium- arrested EC increases the
      number of EC positive for the senescent-associated-beta-galactosidase marker.
      Conversely, down-regulation of MMP-1 expression by small interfering RNAs blunts
      the lithium-dependent increase in senescent-associated-beta-galactosidase
      positive cells. Altogether our data indicate that lithium-induced MMP-1 may
      participate in the reinforcement of EC senescence and reveal a novel mechanism
      for lithium-induced tissue remodeling.

PMID- 19407341
TI  - Prostaglandin E2 stimulates the production of amyloid-beta peptides through
      internalization of the EP4 receptor.
AB  - Amyloid-beta (Abeta) peptides, generated by the proteolysis of beta-amyloid
      precursor protein by beta- and gamma-secretases, play an important role in the
      pathogenesis of Alzheimer disease. Inflammation is also important. We recently
      reported that prostaglandin E(2) (PGE(2)), a strong inducer of inflammation,
      stimulates the production of Abeta through EP(2) and EP(4) receptors, and here we
      have examined the molecular mechanism. Activation of EP(2) and EP(4) receptors is
      coupled to an increase in cellular cAMP levels and activation of protein kinase A
      (PKA). We found that inhibitors of adenylate cyclase and PKA suppress EP(2), but
      not EP(4), receptor-mediated stimulation of the Abeta production. In contrast,
      inhibitors of endocytosis suppressed EP(4), but not EP(2), receptor-mediated
      stimulation. Activation of gamma-secretase was observed with the activation of
      EP(4) receptors but not EP(2) receptors. PGE(2)-dependent internalization of the
      EP(4) receptor was observed, and cells expressing a mutant EP(4) receptor lacking
      the internalization activity did not exhibit PGE(2)-stimulated production of
      Abeta. A physical interaction between the EP(4) receptor and PS-1, a catalytic
      subunit of gamma-secretases, was revealed by immunoprecipitation assays. PGE(2)
      induced internalization of PS-1 and co-localization of EP(4), PS-1, and Rab7 (a
      marker of late endosomes and lysosomes) was observed. Co-localization of PS-1 and
      Rab7 was also observed in the brain of wild-type mice but not of EP(4) receptor
      null mice. These results suggest that PGE(2)-stimulated production of Abeta
      involves EP(4) receptor-mediated endocytosis of PS-1 followed by activation of
      the gamma-secretase, as well as EP(2) receptor-dependent activation of adenylate
      cyclase and PKA, both of which are important in the inflammation-mediated
      progression of Alzheimer disease.

PMID- 19407343
TI  - A novel heuristic for local multiple alignment of interspersed DNA repeats.
AB  - Pairwise local sequence alignment methods have been the prevailing technique to
      identify homologous nucleotides between related species. However, existing
      methods that identify and align all homologous nucleotides in one or more genomes
      have suffered from poor scalability and limited accuracy. We propose a novel
      method that couples a gapped extension heuristic with an efficient filtration
      method for identifying interspersed repeats in genome sequences. During gapped
      extension, we use the MUSCLE implementation of progressive global multiple
      alignment with iterative refinement. The resulting gapped extensions potentially
      contain alignments of unrelated sequence. We detect and remove such undesirable
      alignments using a hidden Markov model (HMM) to predict the posterior probability
      of homology. The HMM emission frequencies for nucleotide substitutions can be
      derived from any time-reversible nucleotide substitution matrix. We evaluate the
      performance of our method and previous approaches on a hybrid data set of real
      genomic DNA with simulated interspersed repeats. Our method outperforms a related
      method in terms of sensitivity, positive predictive value, and localizing
      boundaries of homology. The described methods have been implemented in freely
      available software, Repeatoire, available from:
      http://wwwabi.snv.jussieu.fr/public/Repeatoire.

PMID- 19407342
TI  - A novel mammalian flavin-dependent histone demethylase.
AB  - Methylation of Lys residues on histone proteins is a well known and extensively
      characterized epigenetic mark. The recent discovery of lysine-specific
      demethylase 1 (LSD1) demonstrated that lysine methylation can be dynamically
      controlled. Among the histone demethylases so far identified, LSD1 has the unique
      feature of functioning through a flavin-dependent amine oxidation reaction. Data
      base analysis reveals that mammalian genomes contain a gene (AOF1, for amine
      oxidase flavin-containing domain 1) that is homologous to the LSD1-coding gene.
      Here, we demonstrate that the protein encoded by AOF1 represents a second
      mammalian flavin-dependent histone demethylase, named LSD2. The new demethylase
      is strictly specific for mono- and dimethylated Lys4 of histone H3, recognizes a
      long stretch of the H3 N-terminal tail, senses the presence of additional
      epigenetic marks on the histone substrate, and is covalently inhibited by
      tranylcypromine. As opposed to LSD1, LSD2 does not form a biochemically stable
      complex with the C-terminal domain of the corepressor protein CoREST.
      Furthermore, LSD2 contains a CW-type zinc finger motif with potential zinc
      binding sites that are not present in LSD1. We conclude that mammalian LSD2
      represents a new flavin-dependent H3-Lys4 demethylase that features substrate
      specificity properties highly similar to those of LSD1 but is very likely to be
      part of chromatin-remodeling complexes that are distinct from those involving
      LSD1.

PMID- 19407344
TI  - A framework for multiple kernel support vector regression and its applications to
      siRNA efficacy prediction.
AB  - The cell defense mechanism of RNA interference has applications in gene function
      analysis and promising potentials in human disease therapy. To effectively
      silence a target gene, it is desirable to select appropriate initiator siRNA
      molecules having satisfactory silencing capabilities. Computational prediction
      for silencing efficacy of siRNAs can assist this screening process before using
      them in biological experiments. String kernel functions, which operate directly
      on the string objects representing siRNAs and target mRNAs, have been applied to
      support vector regression for the prediction and improved accuracy over numerical
      kernels in multidimensional vector spaces constructed from descriptors of siRNA
      design rules. To fully utilize information provided by string and numerical data,
      we propose to unify the two in a kernel feature space by devising a multiple
      kernel regression framework where a linear combination of the kernels is used. We
      formulate the multiple kernel learning into a quadratically constrained quadratic
      programming (QCQP) problem, which although yields global optimal solution, is
      computationally demanding and requires a commercial solver package. We further
      propose three heuristics based on the principle of kernel-target alignment and
      predictive accuracy. Empirical results demonstrate that multiple kernel
      regression can improve accuracy, decrease model complexity by reducing the number
      of support vectors, and speed up computational performance dramatically. In
      addition, multiple kernel regression evaluates the importance of constituent
      kernels, which for the siRNA efficacy prediction problem, compares the relative
      significance of the design rules. Finally, we give insights into the multiple
      kernel regression mechanism and point out possible extensions.

PMID- 19407345
TI  - Network-based inference of cancer progression from microarray data.
AB  - Cancer cells exhibit a common phenotype of uncontrolled cell growth, but this
      phenotype may arise from many different combinations of mutations. By inferring
      how cells evolve in individual tumors, a process called cancer progression, we
      may be able to identify important mutational events for different tumor types,
      potentially leading to new therapeutics and diagnostics. Prior work has shown
      that it is possible to infer frequent progression pathways by using gene
      expression profiles to estimate "distances" between tumors. Here, we apply gene
      network models to improve these estimates of evolutionary distance by controlling
      for correlations among coregulated genes. We test three variants of this
      approach: one using an optimized best-fit network, another using sampling to
      infer a high-confidence subnetwork, and one using a modular network inferred from
      clusters of similarly expressed genes. Application to lung cancer and breast
      cancer microarray data sets shows small improvements in phylogenies when
      correcting from the optimized network and more substantial improvements when
      correcting from the sampled or modular networks. Our results suggest that a
      network correction approach improves estimates of tumor similarity, but
      sophisticated network models are needed to control for the large hypothesis space
      and sparse data currently available.

PMID- 19407347
TI  - The gene-duplication problem: near-linear time algorithms for NNI-based local
      searches.
AB  - The gene-duplication problem is to infer a species supertree from a collection of
      gene trees that are confounded by complex histories of gene-duplication events.
      This problem is NP-complete and thus requires efficient and effective heuristics.
      Existing heuristics perform a stepwise search of the tree space, where each step
      is guided by an exact solution to an instance of a local search problem. A
      classical local search problem is the {?tt NNI} search problem, which is based on
      the nearest neighbor interchange operation. In this work, we 1) provide a novel
      near-linear time algorithm for the {?tt NNI} search problem, 2) introduce
      extensions that significantly enlarge the search space of the {?tt NNI} search
      problem, and 3) present algorithms for these extended versions that are
      asymptotically just as efficient as our algorithm for the {?tt NNI} search
      problem. The exceptional speedup achieved in the extended {?tt NNI} search
      problems makes the gene-duplication problem more tractable for large-scale
      phylogenetic analyses. We verify the performance of our algorithms in a
      comparison study using sets of large randomly generated gene trees.

PMID- 19407346
TI  - Generalized gene adjacencies, graph bandwidth, and clusters in yeast evolution.
AB  - We present a parameterized definition of gene clusters that allows us to control
      the emphasis placed on conserved order within a cluster. Though motivated by
      biological rather than mathematical considerations, this parameter turns out to
      be closely related to the bandwidth parameter of a graph. Our focus will be on
      how this parameter affects the characteristics of clusters: how numerous they
      are, how large they are, how rearranged they are, and to what extent they are
      preserved from ancestor to descendant in a phylogenetic tree. We infer the latter
      property by dynamic programming optimization of the presence of individual edges
      at the ancestral nodes of the phylogeny. We apply our analysis to a set of
      genomes drawn from the Yeast Gene Order Browser.

PMID- 19407348
TI  - Designing patterns and profiles for faster HMM search.
AB  - Profile HMMs are powerful tools for modeling conserved motifs in proteins. They
      are widely used by search tools to classify new protein sequences into families
      based on domain architecture. However, the proliferation of known motifs and new
      proteomic sequence data poses a computational challenge for search, requiring
      days of CPU time to annotate an organism's proteome. It is highly desirable to
      speed up HMM search in large databases. We design PROSITE-like patterns and short
      profiles that are used as filters to rapidly eliminate protein-motif pairs for
      which a full profile HMM comparison does not yield a significant match. The
      design of the pattern-based filters is formulated as a multichoice knapsack
      problem. Profile-based filters with high sensitivity are extracted from a profile
      HMM based on their theoretical sensitivity and false positive rate. Experiments
      show that our profile-based filters achieve high sensitivity (near 100 percent)
      while keeping around 20?times speedup with respect to the unfiltered search
      program. Pattern-based filters typically retain at least 90 percent of the
      sensitivity of the source HMM with 30-40?times speedup. The profile-based filters
      have sensitivity comparable to the multistage filtering strategy HMMERHEAD [15]
      and are faster in most of our experiments.

PMID- 19407349
TI  - Fuzzy-adaptive-subspace-iteration-based two-way clustering of microarray data.
AB  - This paper presents Fuzzy-Adaptive-Subspace-Iteration-based Two-way Clustering
      (FASIC) of microarray data for finding differentially expressed genes (DEGs) from
      two-sample microarray experiments. The concept of fuzzy membership is introduced
      to transform the hard adaptive subspace iteration (ASI) algorithm into a fuzzy
      ASI algorithm to perform two-way clustering. The proposed approach follows a
      progressive framework to assign a relevance value to genes associated with each
      cluster. Subsequently, each gene cluster is scored and ranked based on its
      potential to provide a correct classification of the sample classes. These ranks
      are converted into P values using the R-test, and the significance of each gene
      is determined. A fivefold validation is performed on the DEGs selected using the
      proposed approach. Empirical analyses on a number of simulated microarray data
      sets are conducted to quantify the results obtained using the proposed approach.
      To exemplify the efficacy of the proposed approach, further analyses on different
      real microarray data sets are also performed.

PMID- 19407350
TI  - Gene clustering via integrated Markov models combining individual and pairwise
      features.
AB  - Clustering of genes into groups sharing common characteristics is a useful
      exploratory technique for a number of subsequent computational analysis. A wide
      range of clustering algorithms have been proposed in particular to analyze gene
      expression data, but most of them consider genes as independent entities or
      include relevant information on gene interactions in a suboptimal way. We propose
      a probabilistic model that has the advantage to account for individual data
      (e.g., expression) and pairwise data (e.g., interaction information coming from
      biological networks) simultaneously. Our model is based on hidden Markov random
      field models in which parametric probability distributions account for the
      distribution of individual data. Data on pairs, possibly reflecting distance or
      similarity measures between genes, are then included through a graph, where the
      nodes represent the genes, and the edges are weighted according to the available
      interaction information. As a probabilistic model, this model has many
      interesting theoretical features. In addition, preliminary experiments on
      simulated and real data show promising results and points out the gain in using
      such an approach. AVAILABILITY: The software used in this work is written in C++
      and is available with other supplementary material at
      http://mistis.inrialpes.fr/people/forbes/transparentia/supplementary.html.

PMID- 19407351
TI  - Semantics of multimodal network models.
AB  - A multimodal network (MMN) is a novel graph-theoretic formalism designed to
      capture the structure of biological networks and to represent relationships
      derived from multiple biological databases. MMNs generalize the standard notions
      of graphs and hypergraphs, which are the bases of current diagrammatic
      representations of biological phenomena, and incorporate the concept of mode.
      Each vertex of an MMN is a biological entity, a biot, while each modal hyperedge
      is a typed relationship, where the type is given by the mode of the hyperedge.
      The semantics of each modal hyperedge e is given through denotational semantics,
      where a valuation function fe defines the relationship among the values of the
      vertices incident on e. The meaning of an MMN is denoted in terms of the
      semantics of a hyperedge sequence. A companion paper defines MMNs and
      concentrates on the structural aspects of MMNs. This paper develops MMN
      denotational semantics when used as a representation of the semantics of
      biological networks and discusses applications of MMNs in managing complex
      biological data.

PMID- 19407352
TI  - Statistical alignment with a sequence evolution model allowing rate heterogeneity
      along the sequence.
AB  - We present a stochastic sequence evolution model to obtain alignments and
      estimate mutation rates between two homologous sequences. The model allows two
      possible evolutionary behaviors along a DNA sequence in order to determine
      conserved regions and take its heterogeneity into account. In our model, the
      sequence is divided into slow and fast evolution regions. The boundaries between
      these sections are not known. It is our aim to detect them. The evolution model
      is based on a fragment insertion and deletion process working on fast regions
      only and on a substitution process working on fast and slow regions with
      different rates. This model induces a pair hidden Markov structure at the level
      of alignments, thus making efficient statistical alignment algorithms possible.
      We propose two complementary estimation methods, namely, a Gibbs sampler for
      Bayesian estimation and a stochastic version of the EM algorithm for maximum
      likelihood estimation. Both algorithms involve the sampling of alignments. We
      propose a partial alignment sampler, which is computationally less expensive than
      the typical whole alignment sampler. We show the convergence of the two
      estimation algorithms when used with this partial sampler. Our algorithms provide
      consistent estimates for the mutation rates and plausible alignments and sequence
      segmentations on both simulated and real data.

PMID- 19407353
TI  - Visual exploration of three-dimensional gene expression using physical views and
      linked abstract views.
AB  - During animal development, complex patterns of gene expression provide positional
      information within the embryo. To better understand the underlying gene
      regulatory networks, the Berkeley Drosophila Transcription Network Project
      (BDTNP) has developed methods that support quantitative computational analysis of
      three-dimensional (3D) gene expression in early Drosophila embryos at cellular
      resolution. We introduce PointCloudXplore (PCX), an interactive visualization
      tool that supports visual exploration of relationships between different genes'
      expression using a combination of established visualization techniques. Two
      aspects of gene expression are of particular interest: 1) gene expression
      patterns defined by the spatial locations of cells expressing a gene and 2)
      relationships between the expression levels of multiple genes. PCX provides users
      with two corresponding classes of data views: 1) Physical Views based on the
      spatial relationships of cells in the embryo and 2) Abstract Views that discard
      spatial information and plot expression levels of multiple genes with respect to
      each other. Cell Selectors highlight data associated with subsets of embryo cells
      within a View. Using linking, these selected cells can be viewed in multiple
      representations. We describe PCX as a 3D gene expression visualization tool and
      provide examples of how it has been used by BDTNP biologists to generate new
      hypotheses.

PMID- 19407354
TI  - Conditioning-based modeling of contextual genomic regulation.
AB  - A more complete understanding of the alterations in cellular regulatory and
      control mechanisms that occur in the various forms of cancer has been one of the
      central targets of the genomic and proteomic methods that allow surveys of the
      abundance and/or state of cellular macromolecules. This preference is driven both
      by the intractability of cancer to generic therapies, assumed to be due to the
      highly varied molecular etiologies observed in cancer, and by the opportunity to
      discern and dissect the regulatory and control interactions presented by the
      highly diverse assortment of perturbations of regulation and control that arise
      in cancer. Exploiting the opportunities for inference on the regulatory and
      control connections offered by these revealing system perturbations is fraught
      with the practical problems that arise from the way biological systems operate.
      Two classes of regulatory action in biological systems are particularly inimical
      to inference, convergent regulation, where a variety of regulatory actions result
      in a common set of control responses (crosstalk), and divergent regulation, where
      a single regulatory action produces entirely different sets of control responses,
      depending on cellular context (conditioning). We have constructed a coarse
      mathematical model of the propagation of regulatory influence in such
      distributed, context-sensitive regulatory networks that allows a quantitative
      estimation of the amount of crosstalk and conditioning associated with a
      candidate regulatory gene taken from a set of genes that have been profiled over
      a series of samples where the candidate's activity varies.

PMID- 19407355
TI  - Multimodal networks: structure and operations.
AB  - A multimodal network (MMN) is a novel graph-theoretic formalism designed to
      capture the structure of biological networks and to represent relationships
      derived from multiple biological databases. MMNs generalize the standard notions
      of graphs and hypergraphs, which are the bases of current diagrammatic
      representations of biological phenomena and incorporate the concept of mode. Each
      vertex of an MMN is a biological entity, a biot, while each modal hyperedge is a
      typed relationship, where the type is given by the mode of the hyperedge. The
      current paper defines MMNs and concentrates on the structural aspects of MMNs. A
      companion paper develops MMNs as a representation of the semantics of biological
      networks and discusses applications of the MMNs in managing complex biological
      data. The MMN model has been implemented in a database system containing multiple
      kinds of biological networks.

PMID- 19407356
TI  - Optimal aggregation of binary classifiers for multiclass cancer diagnosis using
      gene expression profiles.
AB  - Multiclass classification is one of the fundamental tasks in bioinformatics and
      typically arises in cancer diagnosis studies by gene expression profiling. There
      have been many studies of aggregating binary classifiers to construct a
      multiclass classifier based on one-versus-the-rest (1R), one-versus-one (11), or
      other coding strategies, as well as some comparison studies between them.
      However, the studies found that the best coding depends on each situation.
      Therefore, a new problem, which we call the "optimal coding problem," has arisen:
      how can we determine which coding is the optimal one in each situation? To
      approach this optimal coding problem, we propose a novel framework for
      constructing a multiclass classifier, in which each binary classifier to be
      aggregated has a weight value to be optimally tuned based on the observed data.
      Although there is no a priori answer to the optimal coding problem, our weight
      tuning method can be a consistent answer to the problem. We apply this method to
      various classification problems including a synthesized data set and some cancer
      diagnosis data sets from gene expression profiling. The results demonstrate that,
      in most situations, our method can improve classification accuracy over simple
      voting heuristics and is better than or comparable to state-of-the-art multiclass
      predictors.

PMID- 19407357
TI  - Parallel clustering algorithm for large data sets with applications in
      bioinformatics.
AB  - Large sets of bioinformatical data provide a challenge in time consumption while
      solving the cluster identification problem, and that is why a parallel algorithm
      is so needed for identifying dense clusters in a noisy background. Our algorithm
      works on a graph representation of the data set to be analyzed. It identifies
      clusters through the identification of densely intraconnected subgraphs. We have
      employed a minimum spanning tree (MST) representation of the graph and solve the
      cluster identification problem using this representation. The computational
      bottleneck of our algorithm is the construction of an MST of a graph, for which a
      parallel algorithm is employed. Our high-level strategy for the parallel MST
      construction algorithm is to first partition the graph, then construct MSTs for
      the partitioned subgraphs and auxiliary bipartite graphs based on the subgraphs,
      and finally merge these MSTs to derive an MST of the original graph. The
      computational results indicate that when running on 150 CPUs, our algorithm can
      solve a cluster identification problem on a data set with 1,000,000 data points
      almost 100 times faster than on single CPU, indicating that this program is
      capable of handling very large data clustering problems in an efficient manner.
      We have implemented the clustering algorithm as the software CLUMP.

PMID- 19407358
TI  - Prediction of cancer class with majority voting genetic programming classifier
      using gene expression data.
AB  - In order to get a better understanding of different types of cancers and to find
      the possible biomarkers for diseases, recently, many researchers are analyzing
      the gene expression data using various machine learning techniques. However, due
      to a very small number of training samples compared to the huge number of genes
      and class imbalance, most of these methods suffer from overfitting. In this
      paper, we present a majority voting genetic programming classifier (MVGPC) for
      the classification of microarray data. Instead of a single rule or a single set
      of rules, we evolve multiple rules with genetic programming (GP) and then apply
      those rules to test samples to determine their labels with majority voting
      technique. By performing experiments on four different public cancer data sets,
      including multiclass data sets, we have found that the test accuracies of MVGPC
      are better than those of other methods, including AdaBoost with GP. Moreover,
      some of the more frequently occurring genes in the classification rules are known
      to be associated with the types of cancers being studied in this paper.

PMID- 19407359
TI  - Variability of thiobarbituric acid reacting substances in saliva.
AB  - INTRODUCTION: Salivary TBARS are a potential marker of oxidative stress in the
      oral cavity. Previous studies have found increased levels of salivary TBARS in
      various diseases. The aim of this study was to assess the variability of salivary
      TBARS in both genders. SUBJECTS & METHODS: Saliva samples from thirty-eight
      healthy volunteers (18F & 20M) were collected every day during 30 day period.
      TBARS levels were measured spectrophotometrically using a high-throughput 96-well
      plate method. Time series analysis was performed using standard statistical
      methods. RESULTS: Repeated measures ANOVA showed a significant variation of
      salivary TBARS within day and subjects (p < 0.001). The dynamics did not differ
      between genders. Intraindividual variability was very high in both genders with
      coefficients of variation of more than 60%. Interindividual variability was
      higher in men than in women (73% vs. 46%; p < 0.01). DISCUSSION: The relatively
      high intraindividual variability indicates that the use of salivary TBARS will be
      limited to research on a population level, although some informative value might
      be gained by repeated samplings. Factors influencing the biological variability
      of salivary TBARS should be identified in further studies.

PMID- 19407360
TI  - Could high levels of tissue polypeptide specific antigen, a marker of apoptosis
      detected in nonalcoholic steatohepatitis, improve after weight loss?
AB  - BACKGROUND: Tissue Polypeptide Specific antigen has recently been proposed as
      diagnostic marker of apoptosis in NonAlcoholic SteatoHepatitis. The aim of this
      study was to validate in patients suffering from NonAlcoholic SteatoHepatitis the
      clinical utility of this marker after different programs of weight reduction.
      METHODS: Overweight/obese patients with visceral adiposity and liver histology
      compatible were assigned to a Calorically-Restricted diet (n = 22), a Calorically
      Restricted diet plus EXercise (n = 19) or No Healthy Life Style (control group, n
      = 21) for six months. The presence of Body-Weight loss was assessed by a Body
      Mass Index decrease of at least three points. Serum ALanine aminoTransferase,
      HOmeostasis Model Assessment method value and Tissue Polypeptide Specific antigen
      concentrations were determined at time 0, after 3 and 6 months in both the
      Intervention groups and in the controls' one. RESULTS: In NonAlcoholic
      SteatoHepatitis patients who obtained Body-Weight reduction, a significant
      decrease of the serum Tissue Polypeptide Specific antigen values was showed with
      a clear linear trend across time, P = 0.0001. Decrement of Tissue Polypeptide
      Specific antigen concentrations best differentiated the Body-Weight loss from the
      body-weight maintenance in respect to Tissue Polypeptide Specific antigen and
      HOmeostasis Model Assessment method values. CONCLUSION: This study support the
      clinical utility of serum Tissue Polypeptide Specific antigen antigen levels in
      the follow-up of overweight/obese patients with NonAlcoholic SteatoHepatitis on
      weight reduction programs.

PMID- 19407361
TI  - Temporal patterns of soluble adhesion molecules in cerebrospinal fluid and plasma
      in patients with the acute brain infraction.
AB  - The aim of this study was to define concentration changes of soluble adhesion
      molecules (sICAM-1, sVCAM-1 and sE-Selectin) in cerebrospinal fluid and plasma,
      as well as, number of peripheral blood leukocytes and the albumin coefficient in
      the patients with the acute brain infarction. We also, analyzed the correlation
      between the measured levels, the infarct volume and the degree of neurological
      and the functional deficit. The study included 50 patients with the acute
      cerebral infarction and the control group consisted of 16 patients, age and sex
      matched. Obtained results showed significant increase in number of leukocytes,
      the albumin coefficient and the level of soluble adhesion molecules within the
      first seven days in patients. The highest values of measured parameters were
      noted within the third and the fourth day after the insult, which is the
      suggested period of maximal intensity of inflammatory reactions. Significant
      correlation was found between measured parameters and the infarct volume, the
      degree of neurological and the functional deficit. The results suggest that
      investigated parameters in CSF and blood represent a dynamic index of
      inflammatory events as one of the fundametal mechanisms responsible for neuron
      damage during acute phase of brain infarction.

PMID- 19407362
TI  - Metabolic background determines the importance of NOS3 polymorphisms in
      restenosis after percutaneous coronary intervention: A study in patients with and
      without the metabolic syndrome.
AB  - Variation in the NOS3 gene has been related to the development of restenosis. The
      Glu298Asp polymorphism has previously been investigated for its effect on NO
      levels and the development of restenosis. However, the variability of findings
      gave rise to the hypothesis that the functional significance of this polymorphism
      may only become manifest under conditions of endothelial dysfunction. Since
      patients with the metabolic syndrome are known to have endothelial dysfunction,
      we aimed to investigate if the significance of NOS3 polymorphisms may depend on
      the presence of the metabolic syndrome. We examined the impact of the -949 A/G,
      the -716 C/T and the Glu298Asp polymorphisms in the NOS3 gene on the risk of
      clinical restenosis in a previously described subpopulation of the GENDER-study,
      a multicenter prospective study design that enrolled consecutive patients after
      successful PCI. This subpopulation consisted of 901 patients of whom sufficient
      data were available to establish absence or presence of the metabolic syndrome.
      Of these patients, 448 had the metabolic syndrome. Clinical restenosis, defined
      as target vessel revascularization (TVR), was the primary endpoint. We
      demonstrated that the minor -949G, -716T and 298Asp alleles were associated with
      a significantly increased risk of TVR in patients with the metabolic syndrome
      (HR: 1.58 [95%CI: 1.04-2.40], HR: 1.95 [95%CI: 1.02-3.70] and HR: 1.67 [95%CI:
      1.09-2.54], respectively). In the group without the metabolic syndrome we
      observed no association between the three polymorphisms and TVR.

PMID- 19407363
TI  - GSTM1, GSTM3 and GSTT1 gene variants and risk of benign prostate hyperplasia in
      North India.
AB  - Glutathione S-transferases (GSTs) play an important role in detoxification of
      various toxic compounds like carcinogens in cigarette smoke and tobacco by
      conjugating to toxic compounds and inactivating their hazardous effect. Variation
      in Glutathione S-Transferases (GSTs) genes may alter the catalytic efficiency of
      GST isoenzymes leading to potential increase in cancer susceptibility due to
      various carcinogens. We therefore, investigated association of GSTM1, GSTM3 and
      GSTT1 variants with susceptibility to benign prostate hyperplasia (BPH) and
      cigarette, tobacco chewing and alcohol consumption as confounding factors in 141
      BPH and 184 healthy controls. Results showed increased risk for BPH
      susceptibility in patients with GSTM1 null genotype (OR-2.03, p = 0.013) and
      smoking (OR-3.12, p = 0.028), tobacco chewing (OR-2.54, p = 0.039) and alcohol
      habits (OR-3.39, p = 0.010). Null genotype of GSTM1 with cigarette, tobacco and
      alcohol habits predisposed increased risk for BPH.

PMID- 19407365
TI  - Dual usages of single Wilms' tumor 1 immunohistochemistry in evaluation of breast
      tumors: a preliminary study of 30 cases.
AB  - Our previous studies revealed that Wilms' tumor 1 (WT-1) protein was highly
      expressed in breast myoepithelial (ME) and endothelial cells. As the human breast
      tissue is rich in ME cells and blood vessels, our current study intended to
      assess whether WT-1 immunohistochemistry may have dual usages in evaluation of
      the ME cells and micro-vessel density. Consecutive sections were prepared from
      breast tumors with co-existing normal, hyperplastic, and neoplastic components.
      Consecutive sections were immunostained for WT-1 and a panel of ME and
      endothelial cell markers. From each case, 4-5 randomly selected duct clusters
      were photographed, and the percentages of positive cells for these molecules were
      compared. Similar to ME cell marker CD10 and smooth muscle actin (SMA), WT-1
      expression was preferentially seen in ME cells, and over 90% of WT-1 positive ME
      cells were immunoreactive to CD10 and SMA. Distinct WT-1 expression was also seen
      in endothelial cells, and over 90% of WT-1 positive endothelial cells were
      positive for blood vessel specific markers. With tumor progression, the
      percentage and intensity of WT-1 positivity decreased in ME cells, whereas
      increased in endothelial cells. These finding suggest that WT-1
      immunohistochemistry may be used to assess both the ME cells and micro-vessel
      density.

PMID- 19407364
TI  - HLA haplotype A33-B58-Cw10 may modulate radiographic development of bamboo spine
      in Taiwanese patients with primary ankylosing spondylitis.
AB  - OBJECTIVE: To evaluate the possible relationship between HLA alleles and bony
      ankylosis of the spine (bamboo spine) in Taiwanese patients with ankylosing
      spondylitis (AS). METHODS: A small cohort of HLA-B27 positive AS patients was
      conducted to analyze the effects of alleles {and haplotypes} on the development
      of bamboo spine. DNA typing of HLA class I and class II genes were performed by
      SSP method on primary ankylosing spondylitis patients with bamboo spine (n = 84)
      and spinal enthesopathy controls (n = 228). Odds ratios with 95% confidence
      intervals and P value were estimated. Determination of the most probable HLA
      haplotypes on all patients were constructed by comparison of the alleles carried
      by each patient with the HLA haplotype database established in Taiwanese
      population studies using homozygosity approach [1] and by expectation-maximum
      algorithm [2]. RESULTS: Allele frequencies of HLA A33, B58, Cw10, DR4, DR17 and
      DQ2 were significantly lower in bamboo patients as compared to non-bamboo
      controls. In contrast, allele frequencies of A24, B54, Cw15, DR11 and DR14 were
      significantly higher in bamboo patients. Less remarkably, high frequencies of
      B39, B51, Cw1 and Cw2 alleles were also noted in bamboo patients. Considering
      linkage disequilibria of alleles in haplotypes, HLA-A11-B27-Cw12 was the most
      common haplotype in both bamboo and non-bamboo groups (95.23% vs. 91.22%,
      respectively, P = 0.238). {Haplotypes A33-B58-Cw10, A33-B58-Cw10-DR13 and A33-B58
      Cw10-DR17} were significantly lower in bamboo patients as compared to those in
      controls (P < 0.001, P = 0.001, P = 0.002, respectively). CONCLUSION: Haplotypes
      A33-B58-Cw10, A33-B58-Cw10-DR13 and A33-B58-Cw10-DR17 showed a strong association
      with bamboo spine in Taiwanese AS patients. Detection of such haplotypes might be
      a great aid in the management of patients with the disease.

PMID- 19407366
TI  - Specific demonstration of drug-induced tumour cell apoptosis in human xenografts
      models using a plasma biomarker.
AB  - Pharmacodynamic (PD) assays should be used before advancing new drugs to clinical
      trials. Most PD assays measure the response to drugs in tissue, a procedure which
      requires tissue biopsies. The M30-Apoptosense ELISA is a PD biomarker assay for
      the quantitative determination of caspase-cleaved cytokeratin 18 (CK18) released
      from apoptotic carcinoma cells into blood. We here demonstrate that whereas the
      M30-Apoptosense ELISA assay detects human caspase-cleaved CK18, the mouse and rat
      CK18 caspase cleavage products are detected with low affinity. The M30
      Apoptosense ELISA therefore facilitates the determination of drug-induced
      apoptosis in human tumour xenografts in rodents using plasma samples, largely
      independently from host toxicity. Increases of caspase-cleaved CK18 were observed
      in plasma from different carcinoma xenograft models in response to anticancer
      drugs. The appearance caspase-cleaved CK18 in plasma was found to reflect
      formation of the caspase-cleaved epitope in FaDu head-neck carcinomas and in
      cultured cells. The M30-Apoptosense assay allows determination of tumour response
      in blood from xenograft models and from patients, providing a powerful tool for
      translational studies of anticancer drugs.

PMID- 19407367
TI  - Immunoproteomics reveals that cancer of the tongue and the gingivobuccal complex
      exhibit differential autoantibody response.
AB  - Autoantibody response to tumor antigens has been widely used to identify novel
      tumor markers for different cancers, including that of the head and neck. The
      oral cavity, which is in the head and neck region, comprises of many sub sites
      with distinct biologies and incidence of cancer of each sub site of the oral
      cavity is different. It is anticipated therefore that each sub site of the oral
      cavity may elicit a differential autoantibody response. This report evaluates the
      autoantibody response in 15 patients with cancer of gingivo-buccal complex and in
      15 patients with cancer of tongue using Immunoproteomics, and shows that the
      autoantibody response to alpha-enolase, HSP 70, peroxiredoxin-VI, annexin II,
      pyruvate kinase, alpha-tubulin, beta-tubulin, ATP synthase, triose phosphate
      isomerase and aldose reductase seen in patients with cancer of gingivo-buccal
      complex is absent in patients with cancer of tongue. This suggests that cancer of
      these sub sites should be studied separately because of their different biology
      and emerging site specific molecular signatures including autoantibody responses
      to ensure unambiguous clinical interpretations.

PMID- 19407368
TI  - Cancer cell-expressed immunoglobulins: CA215 as a pan cancer marker and its
      diagnostic applications.
AB  - BACKGROUND: RP215 was the first generated monoclonal antibody which recognizes
      specifically carbohydrate-associated epitope(s) localized in the variable region
      of the cancer cell-expressed immunoglobulin heavy chains, designated in general
      as CA215. Clinical evaluations were performed to assess if RP215 can be utilized
      in immunoassays to determine serum levels of CA215 among ovarian or cervical
      cancer patients for monitoring purposes. METHODS: By using immunoassays, serum
      CA215 levels were determined from cervical or ovarian cancer patients and
      evaluated based on their respective clinical stages as well as the conditions of
      clinical treatments. RESULTS: Multi-center clinical trials were performed with
      frozen serum specimens of patients with ovarian or clinical cancers to determine
      the efficacy of RP215-based immunoassays. In the case of ovarian cancer, CA215
      immunoassay kit has a sensitivity of 46-68% as compared to 46-70% for that of the
      corresponding CA125 kit. When both markers were combined for simultaneous
      monitoring of cancer patients, the sensitivity could be as high as 72-87%.
      Further analysis revealed that serum CA215 levels among cancer patients are well
      correlated with stages of tumor progression as well as surgical or radio/chemo
      treatments. CONCLUSIONS: The results of these multi-center clinical studies
      suggest that CA215 is a suitable pan cancer marker for the monitoring of
      ovarian/cervical cancers and maybe of several others which express CA215 and can
      be detected in human circulations.

PMID- 19407369
TI  - Translation of an STR-based biomarker into a clinically compatible SNP-based
      platform for loss of heterozygosity.
AB  - Loss of heterozygosity (LOH) has been shown to be a promising biomarker of cancer
      risk in patients with premalignant conditions. In this study we describe
      analytical validation in clinical biopsy samples of a SNP-based pyrosequencing
      panel targeting regions of LOH on chromosomes 17p and 9p including TP53 and
      CDKN2A tumor suppressor genes. Assays were tested for analytic specificity,
      sensitivity, efficiency, and reproducibility. Accuracy was evaluated by comparing
      SNP-based LOH results to those obtained by previously well-studied short tandem
      repeat polymorphisms (STRs) in DNA derived from different tissue sources
      including fresh-frozen endoscopic biopsies, samples from surgical resections, and
      formalin-fixed paraffin-embedded sections. A 17p/9p LOH panel comprised of 43
      SNPs was designed to amplify with universal assay conditions in a two-step PCR
      and sequence-by-synthesis reaction that can be completed in two hours and 10
      minutes. The methods presented can be a model for developing a SNP-based LOH
      approach targeted to any chromosomal region of interest for other premalignant
      conditions and this panel could be incorporated as part of a biomarker for cancer
      risk prediction, early detection, or as entry criteria for randomized trials.

PMID- 19407370
TI  - Structure of pig heart citrate synthase at 1.78 A resolution.
AB  - Pig heart citrate synthase was crystallized from a small-molecule cocktail
      containing cystamine dihydrochloride, aspartame and benzamidine hydrochloride.
      The structure was refined to an R factor of 0.179 (R(free) = 0.222) using
      synchrotron data to a resolution of 1.78 A. The model includes the full-length
      protein, a chloride ion, a sulfate ion, 305 water molecules and an unexpected
      moiety attached through a disulfide linkage to Cys184, which was modeled as a
      half-cystamine molecule generated by disulfide exchange with the cystamine in the
      small-molecule cocktail.

PMID- 19407371
TI  - Structure of N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) from
      Mycobacterium tuberculosis in a cubic space group.
AB  - GlmU is a bifunctional enzyme that catalyzes the final two steps in the
      biosynthesis of UDP-GlcNAc. Crystals of GlmU from Mycobacterium tuberculosis
      obtained using ammonium sulfate as a precipitant diffracted poorly (to 3.4 A
      resolution) and displayed an unusually high solvent content (>80%) with sparse
      crystal packing that resulted in large solvent channels. With one molecule per
      asymmetric unit, the monomers from three neighbouring asymmetric units related by
      the crystal threefold formed a biological trimer. Although this is the first
      report of the structure of GlmU determined in a cubic crystal form, the trimeric
      arrangement here is similar to that observed for other GlmU structures determined
      in hexagonal (H3, H32, P6(3)22) space groups.

PMID- 19407372
TI  - Structure of full-length ubiquitin-conjugating enzyme E2-25K (huntingtin
      interacting protein 2).
AB  - The ubiquitin-conjugating enzyme E2-25K has been identified as a huntingtin (the
      key protein in Huntington's disease) interacting protein and has been shown to
      play a role in mediating the toxicity of Abeta, the principal protein involved in
      Alzheimer's disease pathogenesis. E2-25K is a dual-domain protein with an
      ubiquitin-associated (UBA) domain as well as a conserved ubiquitin-conjugating
      (UBC) domain which catalyzes the formation of a covalent bond between the C
      terminal glycine of an ubiquitin molecule and the -amine of a lysine residue on
      the acceptor protein as part of the ubiquitin-proteasome pathway. The crystal
      structures of E2-25K M172A mutant protein at pH 6.5 and pH 8.5 were determined to
      1.9 and 2.2 A resolution, respectively. Examination of the structures revealed
      domain-domain interactions between the UBC and UBA domains which have not
      previously been reported.

PMID- 19407373
TI  - Structure of the human Nac1 POZ domain.
AB  - Nac1 is a POZ-domain transcription factor that is involved in the self-renewal of
      embryonic stem cells. It is overexpressed in ovarian serous carcinoma and
      targeting the interactions of its POZ domain is a potential therapeutic strategy.
      Nac1 lacks a zinc-finger DNA-binding domain and thereby differs from most other
      POZ-domain transcription factors. Here, the crystal structure of the Nac1 POZ
      domain at 2.1 A resolution is reported. The Nac1 POZ domain crystallized as a
      dimer in which the interaction interfaces between subunits resemble those found
      in the POZ-zinc finger transcription factors. The organization of the Nac1 POZ
      domain core resembles reported POZ-domain structures, whereas the C-terminus
      differs markedly. The C-terminal alpha-helix of the Nac1 POZ domain is shorter
      than that observed in most other POZ-domain transcription factors; variation in
      the organization of this region may be a general feature of POZ-domain
      structures.

PMID- 19407375
TI  - Structure of TTHA1623, a novel metallo-beta-lactamase superfamily protein from
      Thermus thermophilus HB8.
AB  - TTHA1623 is a metallo-beta-lactamase superfamily protein from the extremely
      thermophilic bacterium Thermus thermophilus HB8. Homologues of TTHA1623 exist in
      a wide range of bacteria and archaea and one eukaryote, Giardia lamblia, but
      their function remains unknown. To analyze the structural properties of TTHA1623,
      the crystal structures of its iron-bound and zinc-bound forms have been
      determined to 2.8 and 2.2 A resolution, respectively. TTHA1623 possesses an
      alphabetabetaalpha-fold similar to that of other metallo-beta-lactamase
      superfamily proteins with glyoxalase II-type metal coordination. However,
      TTHA1623 exhibits a putative substrate-binding pocket with a unique shape.

PMID- 19407374
TI  - Geobacillus stearothermophilus 6-phosphogluconate dehydrogenase complexed with 6
      phosphogluconate.
AB  - Two crystal structures of recombinant Geobacillus stearothermophilus 6
      phosphogluconate dehydrogenase (Gs6PDH) in complex with the substrate 6
      phosphogluconate have been determined at medium resolution. Gs6PDH shares
      significant sequence identity and structural similarity with the enzymes from
      Lactococcus lactis, sheep liver and the protozoan parasite Trypanosoma brucei,
      for which a range of structures have previously been reported. Comparisons
      indicate that amino-acid sequence conservation is more pronounced in the two
      domains that contribute to the architecture of the active site, namely the N
      terminal and C-terminal domains, compared with the central domain, which is
      primarily involved in the subunit-subunit associations required to form a stable
      dimer. The active-site residues are highly conserved, as are the interactions
      with the 6-phosphogluconate. There is interest in 6PDH as a potential drug target
      for the protozoan parasite T. brucei, the pathogen responsible for African
      sleeping sickness. The recombinant T. brucei enzyme has proven to be recalcitrant
      to enzyme-ligand studies and a surrogate protein might offer new opportunities to
      investigate and characterize 6PDH inhibitors. The high degree of structural
      similarity, efficient level of expression and straightforward crystallization
      conditions mean that Gs6PDH may prove to be an appropriate model system for
      structure-based inhibitor design targeting the enzyme from Trypanosoma species.

PMID- 19407376
TI  - Cloning, expression, crystallization and preliminary X-ray crystallographic
      analysis of beta-ketoacyl-ACP synthase III (FabH) from Xanthomonas oryzae pv.
      oryzae.
AB  - The bacterial beta-ketoacyl-ACP synthase III (KASIII) encoded by the gene fabH
      (Xoo4209) from Xanthomonas oryzae pv. oryzae, a plant pathogen, is an important
      enzyme in the elongation steps of fatty-acid biosynthesis. It is expected to be
      one of the enzymes responsible for bacterial blight (BB), a serious disease that
      results in huge production losses of rice. As it represents an important target
      for the development of new antibacterial drugs against BB, determination of the
      crystal structure of the KAS III enzyme is essential in order to understand its
      reaction mechanism. In order to analyze the structure and function of KAS III,
      the fabH (Xoo4209) gene was cloned and the enzyme was expressed and purified. The
      KASIII crystal diffracted to 2.05 A resolution and belonged to the orthorhombic
      space group P2(1)2(1)2, with unit-cell parameters a = 69.8, b = 79.5, c = 62.3 A.
      The unit-cell volume of the crystal is compatible with the presence of a single
      monomer in the asymmetric unit, with a corresponding Matthews coefficient V(M) of
      2.27 A(3) Da(-1) and a solvent content of 45.8%.

PMID- 19407377
TI  - Expression, refolding, crystallization and preliminary X-ray analysis of
      Pseudomonas aeruginosa AlgE.
AB  - AlgE is an outer membrane protein present in alginate-producing (mucoid)
      Pseudomonas aeruginosa. AlgE has been overexpressed in insoluble inclusion
      bodies, purified under denaturing conditions and refolded in a buffer containing
      decyl beta-D-maltopyranoside. Purified refolded AlgE was detergent-exchanged into
      n-octyl tetraoxyethylene and diffraction-quality crystals were grown using the
      hanging-drop vapor-diffusion method. The crystals grew as small hexagons with
      unit-cell parameters a = 98.8, b = 156.8, c = 90.4 A, alpha = beta = gamma = 90.0
      degrees . The crystals exhibited the symmetry of space group C222 and diffracted
      to a minimum d-spacing of 3.0 A. On the basis of the Matthews coefficient (V(M) =
      3.28 A(3) Da(-1)), one molecule is estimated to be present in the asymmetric
      unit.

PMID- 19407378
TI  - Production, crystallization and preliminary X-ray diffraction analysis of the
      allergen Can f 2 from Canis familiaris.
AB  - The allergen Can f 2 from dog (Canis familiaris) present in saliva, dander and
      fur is an important cause of allergic sensitization worldwide. Here, the
      production, isolation, crystallization and preliminary X-ray diffraction analysis
      of two crystal forms of recombinant Can f 2 are reported. The first crystal form
      belonged to space group C222, with unit-cell parameters a = 68.7, b = 77.3, c =
      65.1 A, and diffracted to 1.55 A resolution, while the second crystal form
      belonged to space group C2, with unit-cell parameters a = 75.7, b = 48.3, c =
      68.7 A, beta = 126.5 degrees , and diffracted to 2.1 A resolution. Preliminary
      data analysis indicated the presence of a single molecule in the asymmetric unit
      for both crystal forms.

PMID- 19407379
TI  - Crystallization and preliminary X-ray crystallographic analysis of a novel
      histidinol-phosphate phosphatase from Thermococcus onnurineus NA1.
AB  - The TON_0887 gene product from Thermococcus onnurineus NA1 is a 240-residue
      protein that has histidinol-phosphate phosphatase (HolPase) activity. According
      to analysis of its primary structure, the TON_0887 gene product is a
      monofunctional HolPase that belongs to the DDDD superfamily. This contrasts with
      the generally accepted classification that bifunctional HolPases belong to the
      DDDD superfamily. The TON_0887 gene product was purified and crystallized at 295
      K. A 2.2 A resolution data set was collected using synchrotron radiation. The TON
      HolPase crystals belonged to space group P222(1), with unit-cell parameters a =
      40.88, b = 46.89, c = 148.03 A. Assuming the presence of one molecule in the
      asymmetric unit, the solvent content was estimated to be about 48.3%.

PMID- 19407380
TI  - Crystallization and preliminary X-ray analysis of glutathione transferases from
      cyanobacteria.
AB  - Glutathione S-transferases (GSTs) are a group of multifunctional enzymes that are
      found in animals, plants and microorganisms. Their primary function is to remove
      toxins derived from exogenous sources or the products of metabolism from the
      cell. Mammalian GSTs have been extensively studied, in contrast to bacterial GSTs
      which have received relatively scant attention. A new class of GSTs called Chi
      has recently been identified in cyanobacteria. Chi GSTs exhibit a high
      glutathionylation activity towards isothiocyanates, compounds that are normally
      found in plants. Here, the crystallization of two GSTs are presented: TeGST
      produced by Thermosynechococcus elongates BP-1 and SeGST from Synechococcus
      elongates PCC 6301. Both enzymes formed crystals that diffracted to high
      resolution and appeared to be suitable for further X-ray diffraction studies. The
      structures of these GSTs may shed further light on the evolution of GST catalytic
      activity and in particular why these enzymes possess catalytic activity towards
      plant antimicrobial compounds.

PMID- 19407381
TI  - Cloning, purification, crystallization and preliminary X-ray analysis of the
      receiver domain of the histidine kinase CKI1 from Arabidopsis thaliana.
AB  - The receiver domain (RD) of a sensor histidine kinase (HK) catalyses the
      transphosphorylation reaction during the action of HKs in hormonal and abiotic
      signalling in plants. Crystals of the recombinant RD of the Arabidopsis thaliana
      HK CYTOKININ-INDEPENDENT1 (CKI1(RD)) have been obtained by the hanging-drop
      vapour-diffusion method using ammonium sulfate as a precipitant and glycerol as a
      cryoprotectant. The crystals diffracted to approximately 2.4 A resolution on
      beamline BW7B of the DORIS-III storage ring. The diffraction improved
      significantly after the use of a non-aqueous cryoprotectant. Crystals soaked in
      Paratone-N diffracted to at least 2.0 A resolution on beamline BW7B and their
      mosaicity decreased more than tenfold. The crystals belonged to space group
      C222(1), with unit-cell parameters a = 54.46, b = 99.82, c = 79.94 A. Assuming
      the presence of one molecule of the protein in the asymmetric unit gives a
      Matthews coefficient V(M) of 2.33 A(3) Da(-1). A molecular-replacement solution
      has been obtained and structure refinement is in progress.

PMID- 19407382
TI  - Crystallization of human complement component C3b in the presence of a
      staphylococcal complement-inhibitor protein (SCIN).
AB  - Staphylococcus aureus secretes a number of small proteins that effectively
      attenuate the human innate immune response. Among these, the staphylococcal
      complement-inhibitor protein (SCIN) disrupts the function of the complement
      component 3 (C3) convertase that is initiated through either the classical or the
      alternative pathway and thereby prevents amplification of the complement response
      on the bacterial surface. Recent studies have shown that SCIN may affect the
      activities of the C3 convertase by binding in an equimolar fashion to C3b, which
      is itself an integral although non-enzymatic component of the convertase. In
      order to better understand the nature of the C3b-SCIN interaction, the hanging
      drop vapor-diffusion technique was used to crystallize human C3b in the presence
      of a recombinant form of SCIN. These crystals diffracted synchrotron X-rays to
      approximately 6 A Bragg spacing and grew in a primitive tetragonal space group
      (P4(1)2(1)2 or P4(3)2(1)2; unit-cell parameters a = b = 128.03, c = 468.59 A).
      Cell-content analysis of these crystals was consistent with the presence of
      either two 1:1 complexes or a single 2:2 assembly in the asymmetric unit, both of
      which correspond to a solvent content of 51.9%. By making use of these crystals,
      solution of the C3b-SCIN structure should further our understanding of complement
      inhibition and immune evasion by this pathogen.

PMID- 19407383
TI  - Crystallization and preliminary X-ray analysis of a bifunctional catalase-phenol
      oxidase from Scytalidium thermophilum.
AB  - Catalase-phenol oxidase from Scytalidium thermophilum is a bifunctional enzyme:
      its major activity is the catalase-mediated decomposition of hydrogen peroxide,
      but it also catalyzes phenol oxidation. To understand the structural basis of
      this dual functionality, the enzyme, which has been shown to be a tetramer in
      solution, has been purified by anion-exchange and gel-filtration chromatography
      and has been crystallized using the hanging-drop vapour-diffusion technique.
      Streak-seeding was used to obtain larger crystals suitable for X-ray analysis.
      Diffraction data were collected to 2.8 A resolution at the Daresbury Synchrotron
      Radiation Source. The crystals belonged to space group P2(1) and contained one
      tetramer per asymmetric unit.

PMID- 19407384
TI  - Preliminary X-ray crystallographic studies of yeast Get3.
AB  - Tail-anchored (TA) proteins contain a single transmembrane domain (TMD) at the C
      terminus. The post-translational insertion of TA proteins into the ER membrane
      requires the cooperation of the Golgi ER-trafficking (GET) complex, which
      contains Get1, Get2 and Get3. Get3 is a cytosolic ATPase which can recognize and
      bind the TMD of the TA proteins. Get1 and Get2 are ER transmembrane proteins
      which can recruit and form a complex with TA-bound Get3. The GET complex carries
      out an energy-dependent process that facilitates the insertion of the TA-protein
      TMD into the ER membrane. In order to investigate the mechanism by which the GET
      complex functions to promote protein insertion into the ER membrane, yeast Get3
      has been crystallized. The crystals diffracted to 2.7 A resolution using a
      synchrotron X-ray source. The crystals belonged to space group P2(1)2(1)2, with
      unit-cell parameters a = 220.26, b = 112.95, c = 48.27 A. There is one Get3 dimer
      in the asymmetric unit, which corresponds to a solvent content of approximately
      65%.

PMID- 19407385
TI  - Expression, purification, crystallization and preliminary crystallographic
      analysis of laminin-binding protein (Lmb) from Streptococcus agalactiae.
AB  - Laminin-binding protein (Lmb), a surface-exposed lipoprotein from Streptococcus
      agalactiae (group B streptococcus), mediates attachment to human laminin and
      plays a crucial role in the adhesion/invasion of eukaryotic host cells. However,
      the structural basis of laminin binding still remains unclear. In the context of
      detailed structural analysis, the lmb gene has been cloned, expressed in
      Escherichia coli, purified and crystallized. The crystals diffracted to a
      resolution of 2.5 A and belonged to the monoclinic space group P2(1), with unit
      cell parameters a = 56.63, b = 70.60, c = 75.37 A, beta = 96.77 degrees .

PMID- 19407386
TI  - Preliminary joint neutron and X-ray crystallographic study of human carbonic
      anhydrase II.
AB  - Carbonic anhydrases catalyze the interconversion of CO(2) to HCO(3)(-), with a
      subsequent proton-transfer (PT) step. PT proceeds via a proposed hydrogen-bonded
      water network in the active-site cavity that is stabilized by several hydrophilic
      residues. A joint X-ray and neutron crystallographic study has been initiated to
      determine the specific water network and the protonation states of the
      hydrophilic residues that coordinate it in human carbonic anhydrase II. Time-of
      flight neutron crystallographic data have been collected from a large (
      approximately 1.2 mm(3)) hydrogen/deuterium-exchanged crystal to 2.4 A resolution
      and X-ray crystallographic data have been collected from a similar but smaller
      crystal to 1.5 A resolution. Obtaining good-quality neutron data will contribute
      to the understanding of the catalytic mechanisms that utilize water networks for
      PT in protein environments.

PMID- 19407387
TI  - Crystallization and crystallographic analysis of Bacillus subtilis xylanase C.
AB  - The recent biochemical characterization of the xylanases of glycosyl hydrolase
      family 5 (GH 5) has identified a distinctive endo mode of action, hydrolyzing the
      beta-1,4 xylan chain at a specific site directed by the position of an alpha-1,2
      linked glucuronate moiety. Xylanase C (XynC), the GH 5 xylanase from Bacillus
      subtilis 168, has been cloned, overexpressed and crystallized. Initial data
      collection was performed and a preliminary model has been built into a low
      quality 2.7 A resolution density map. The crystals belonged to the primitive
      monoclinic space group P2(1). Further screening identified an additive that
      resulted in large reproducible crystals. This larger more robust crystal form
      belonged to space group P2(1)2(1)2 and a resulting data set has been processed to
      1.64 A resolution. This will be the second structure to be solved from this
      unique xylanase family and the first from a Gram-positive bacterium. This work
      may help to identify the structural determinants that allow the exceptional
      specificity of this enzyme and the role it plays in the biological
      depolymerization and processing of glucuronoxylan.

PMID- 19407389
TI  - Crystallization and preliminary X-ray diffraction analysis of the tRNA
      modification enzyme GidA from Aquifex aeolicus.
AB  - The 5-carboxymethylaminomethyl modification of uridine at the first position of
      the tRNA anticodon is crucial for accurate protein synthesis by stabilizing the
      correct codon-anticodon pairing on the ribosome. Two conserved enzymes, GidA and
      MnmE, are involved in this modification process. Aquifex aeolicus GidA was
      crystallized in two different crystal forms: forms I and II. These crystals
      diffracted to 3.2 and 2.3 A resolution, respectively, using synchrotron radiation
      at the Photon Factory. These crystals belonged to space groups I2(1)2(1)2(1) and
      P2(1) with unit-cell parameters a = 101.6, b = 213.3, c = 231.7 A and a = 119.4,
      b = 98.0, c = 129.6 A, beta = 90.002 degrees , respectively. The asymmetric units
      of these crystals are expected to contain two and four molecules, respectively.

PMID- 19407388
TI  - Purification, crystallization and data collection of the apoptotic nuclease
      endonuclease G.
AB  - Endonuclease G (EndoG) is a mitochondrial enzyme that responds to apoptotic
      stimuli by translocating to the nucleus and cleaving chromosomal DNA. EndoG is
      the main apoptotic endonuclease in the caspase-independent pathway. Mouse EndoG
      without the mitochondrial localization signal (amino-acid residues 1-43) was
      successfully overexpressed, purified and crystallized using a microbatch method
      under oil. The initial crystal (type I) was grown in the presence of the
      detergent CTAB and diffracted to 2.8 A resolution, with unit-cell parameters a =
      72.20, b = 81.88, c = 88.66 A, beta = 97.59 degrees in a monoclinic space group.
      The crystal contained two monomers in the asymmetric unit, with a predicted
      solvent content of 46.6%. Subsequent mutation of Cys110 improved the stability of
      the protein significantly and produced further crystals of types II, III and IV
      with space groups C2, P4(1)2(1)2 (or P4(3)2(1)2) and P2(1)2(1)2(1), respectively,
      in various conditions. This suggests the critical involvement of this conserved
      cysteine residue in the crystallization process.

PMID- 19407390
TI  - Crystallization and preliminary X-ray diffraction analysis of a protease
      resistant mutant form of human galectin-8.
AB  - A crystal of a protease-resistant mutant form of human galectin-8, a tandem
      repeat-type galectin with two carbohydrate-recognition domains, was obtained
      using the hanging-drop method and was found to belong to the tetragonal space
      group P4(3)2(1)2, with unit-cell parameters a = 78.93, b = 78.93, c = 132.05 A.
      Diffraction data were collected to a resolution of 3.4 A.

PMID- 19407391
TI  - Crystallization and preliminary crystallographic analysis of the cell-surface
      alginate-binding protein Algp7 isolated from Sphingomonas sp. A1.
AB  - Sphingomonas sp. A1, a Gram-negative bacterium, directly internalizes alginate
      macromolecules through a mouth-like pit that is present on its cell surface. The
      alginate-binding protein Algp7, which was found to be localized on the cell
      surface, contributes to the accumulation of alginate in the pit. Algp7 was
      crystallized at 293 K by means of the sitting-drop vapour-diffusion method with
      polyethylene glycol 3350 as a crystallizing agent. Preliminary X-ray analysis
      showed that the Algp7 crystal belonged to space group P2(1)2(1)2(1), with unit
      cell parameters a = 50.1, b = 98.0, c = 100.1 A, and that it diffracted to 2.8 A
      resolution.

PMID- 19407392
TI  - Purification and preliminary X-ray crystallographic studies of beta
      microseminoprotein from human seminal plasma.
AB  - beta-Microseminoprotein (beta-MSP) is a small cysteine-rich protein with a
      molecular mass of 10 kDa. It was first isolated from human seminal plasma and has
      subsequently been identified from several species. Comparison of the amino-acid
      sequences of beta-MSP proteins suggests that the protein is a rapidly evolving
      protein. The function of beta-MSP is poorly understood. Furthermore, no crystal
      structure has been reported of any beta-MSP; therefore, determination of the
      crystal structure of beta-MSP is the foremost task in order to understand the
      function of this protein completely. Here, the purification, crystallization and
      preliminary X-ray diffraction analysis of beta-MSP from human seminal plasma are
      described. The protein was purified using anion-exchange and size-exclusion
      chromatography and the purified protein was crystallized using 0.1 M ammonium
      sulfate, 0.1 M HEPES buffer pH 7.0 and 20%(w/v) PEG 3350. The crystals belonged
      to the tetragonal space group P4(3)22 and contained three beta-MSP molecules in
      the asymmetric unit. X-ray intensity data were collected to 2.4 A resolution.

PMID- 19407393
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of a
      plant subtilase.
AB  - The subtilase SBT3 from Solanum lycopersicum (tomato) was purified from a tomato
      cell culture and crystallized using the sitting-drop vapour-diffusion method. A
      native data set was collected to 2.5 A resolution at 100 K using synchrotron
      radiation. For experimental phasing, CsCl-derivative and
      tetrakis(acetoxymercuri)methane (TAMM) derivative crystals were employed for
      MIRAS phasing. Three caesium sites and one TAMM site were identified, which
      allowed solution of the structure.

PMID- 19407395
TI  - Cloning, expression, purification and crystallization as well as X-ray
      fluorescence and preliminary X-ray diffraction analyses of human ADP
      ribosylhydrolase 1.
AB  - Human ADP-ribosylhydrolase 1 (hARH1, ADPRH) cleaves the glycosidic bond of ADP
      ribose attached to an Arg residue of a protein. hARH1 has been cloned, expressed
      heterologously in Escherichia coli, purified and crystallized in complex with
      K(+) and ADP. The orthorhombic crystals contained one monomer per asymmetric
      unit, exhibited a solvent content of 43% and diffracted X-rays to a resolution of
      1.9 A. A prerequisite for obtaining well diffracting crystals was the performance
      of X-ray fluorescence analysis on poorly diffracting apo hARH1 crystals, which
      revealed the presence of trace amounts of K(+) in the crystal. Adding K-ADP to
      the crystallization cocktail then resulted in a crystal of different morphology
      and with dramatically improved diffraction properties.

PMID- 19407394
TI  - Expression, crystallization and preliminary crystallographic study of human
      coronavirus HKU1 nonstructural protein 9.
AB  - Human coronavirus HKU1 (HCoV-HKU1) belongs to coronavirus group II and encodes 16
      nonstructural proteins (nsps) which mediate genome replication and transcription.
      Among these nsps, nsp9 has been shown to possess single-stranded DNA/RNA-binding
      properties. The gene that encodes HCoV-HKU1 nsp9 was cloned and expressed in
      Escherichia coli and the protein was subjected to crystallization trials. The
      crystals diffracted to 2.7 A resolution and belonged to space group P2(1)2(1)2,
      with unit-cell parameters a = 83.5, b = 88.4, c = 31.2 A, alpha = beta = gamma =
      90 degrees and two molecules per asymmetric unit.

PMID- 19407396
TI  - Crystallization of a nonclassical Kazal-type Carcinoscorpius rotundicauda serine
      protease inhibitor, CrSPI-1, complexed with subtilisin.
AB  - Serine proteases play a major role in host-pathogen interactions. The innate
      immune system is known to respond to invading pathogens in a nonspecific manner.
      The serine protease cascade is an essential component of the innate immune system
      of the horseshoe crab. The serine protease inhibitor CrSPI isoform 1 (CrSPI-1), a
      unique nonclassical Kazal-type inhibitor of molecular weight 9.3 kDa, was
      identified from the hepatopancreas of the horseshoe crab Carcinoscorpius
      rotundicauda. It potently inhibits subtilisin and constitutes a powerful innate
      immune defence against invading microbes. Here, the cloning, expression,
      purification and cocrystallization of CrSPI-1 with subtilisin are reported. The
      crystals diffracted to 2.6 A resolution and belonged to space group P2(1), with
      unit-cell parameters a = 73.8, b = 65.0, c = 111.9 A, beta = 95.4 degrees . The
      Matthews coefficient (V(M) = 2.64 A(3) Da(-1), corresponding to 53% solvent
      content) and analysis of the preliminary structure solution indicated the
      presence of one heterotrimer (1:2 ratio of CrSPI-1:subtilisin) and one free
      subtilisin molecule in the asymmetric unit.

PMID- 19407398
TI  - GeTe(2)O(6), a germanium tellurate(IV) with an open framework.
AB  - The structure of an already evidenced but still uncharacterized GeTe(2)O(6) phase
      consists of isolated GeO(6) octahedra connected via isolated TeO(3) units. The
      germanium cations occupy a site with 1 symmetry. The Te and O atoms are in
      general positions of the P2(1)/n space group. This structure corresponds to a new
      type of tetravalent tellurate and is different from other AB(2)X(6) structures in
      which the B cation presents a stereochemically active electronic lone pair. It
      derives from the pseudo-hexagonal MI(2)O(6) (M = Mg, Mn, Co and Fe) type by a
      strong monoclinic distortion caused by the much smaller size of Ge(4+) compared
      with the divalent M cations.

PMID- 19407397
TI  - Purification, crystallization and preliminary X-ray analysis of isocitrate
      dehydrogenase kinase/phosphatase from Escherichia coli.
AB  - The Escherichia coli aceK gene encodes isocitrate dehydrogenase
      kinase/phosphatase (EC 2.7.11.5), a bifunctional protein that phosphorylates and
      dephosphorylates isocitrate dehydrogenase (IDH), resulting in its inactivation
      and activation, respectively. This reversible (de)phosphorylation directs
      isocitrate, an intermediate of the citric acid cycle, to either go through the
      full cycle or to enter the glyoxylate bypass. In the present study, the AceK
      protein from E. coli has been purified and crystallized. Three crystal forms were
      obtained from very similar crystallization conditions. The crystals belong to
      space groups P4(1)2(1)2, P3(2)21 and P2(1)2(1)2(1) and diffracted X-rays to
      resolutions of 2.9, 3.0 and 2.7 A, respectively.

PMID- 19407399
TI  - K(3)(Sc(0.875)Nb(0.125))Nb(2)O(9)H(1.75): a new scandium niobate with a unique
      cage structure.
AB  - Potassium scandium niobate hydroxide, K(3)(Sc(0.875)Nb(0.125))Nb(2)O(9)H(1.75),
      is a new scandium niobate with a unique cage structure. The structure contains
      two non-equivalent K(+) sites (3m and 6m2 site symmetry), one disordered
      Sc(3+)/Nb(5+) site (3m site symmetry), one Nb(5+) site (3m site symmetry), two
      O(2-) sites (m and mm2 site symmetry) and one H(+) site (m site symmetry). Both
      scandium and niobium have octahedral environments, which combine to form cages
      around potassium. One K atom lies in a cube-like cage built of seven octahedra,
      while the other K atom is encapsulated by an eight-membered trigonal face
      bicapped prism. The cages form sheets that extend along the ab plane.

PMID- 19407400
TI  - Lithium zincopyrophosphate, Li(2)Zn(3)(P(2)O(7))(2).
AB  - The title compound, dilithium(I) trizinc(II) bis[diphosphate(4-)], is the first
      quaternary lithium zincopyrophosphate in the Li-Zn-P-O system. It features zigzag
      chains running along c, which are built up from edge-sharing [ZnO(5)] trigonal
      bipyramids. One of the two independent Zn sites is fully occupied, whereas the
      other is statistically disordered by Zn(2+) and Li(+) cations, although the two
      Zn sites have similar coordination environments. Li(+) cations occupy a four
      coordinated independent site with an occupancy factor of 0.5, as well as being
      disordered on the partially occupied five-coordinated Zn site with a Zn(2+)/Li(+)
      ratio of 1:1.

PMID- 19407401
TI  - Poly[[(pentaethylenehexamine)manganese(II)] [hepta-mu-selenido-tritin(IV)]]: a
      tin-selenium net with remarkable flexibility.
AB  - The title compound, {[Mn(C(10)H(28)N(6))][Sn(3)Se(7)]}(n), consists of anionic
      (infinity){[Sn(3)Se(7)](2-)} layers interspersed by [Mn(peha)](2+) complex
      cations (peha is pentaethylenehexamine). Pseudocubic (Sn(3)Se(4)) cluster units
      within each layer are held together to form a 6(3) net with a hole size of 8.74 x
      13.87 A. Weak N-H...Se interactions between the host inorganic frameworks and
      metal complexes extend the components into a three-dimensional network. The
      incorporation of metal complexes into the flexible anion layer dictates the
      distortion of the holes.

PMID- 19407403
TI  - A cyanide-bridged Fe(II)-Nd(III) bimetallic assembly with a one-dimensional
      ladder-like chain structure.
AB  - The title complex, catena-poly[[[(2,2'-bipyridine-1kappa(2)N,N')tris(methanol
      2kappaO)(nitrato-2kappa(2)O,O')-mu-cyanido-1:2C:N-cyanido-1kappaC
      iron(II)neodymium(III)]-di-mu-cyanido-1:2'C:N;2:1'N:C] methanol solvate],
      {[Fe(II)Nd(III)(CN)(4)(NO(3))(C(10)H(8)N(2))(CH(3)OH)(3)].CH(3)OH}(n), is made up
      of ladder-like one-dimensional chains oriented along the c axis. Each ladder
      consists of two strands based on alternating Fe(II) and Nd(III) centers connected
      by cyanide bridges. Furthermore, two such parallel chains are connected by
      additional cyanide cross-pieces (the ;rungs' of the ladder), which likewise
      connect Fe(II) and Nd(III) centers, such that each [Fe(CN)(4)(bipy)](2-) unit
      (bipy is 2,2'-bipyridine) coordinates with three Nd(III) centers and each Nd(III)
      center connects with three different [Fe(CN)(4)(bipy)](2-) units. In the complex,
      the iron(II) cation is six-coordinated with a distorted octahedral geometry and
      the neodymium(III) cation is eight-coordinated with a distorted dodecahedral
      environment.

PMID- 19407402
TI  - A diketiminate-bound diiron complex with a bridging carbonate ligand.
AB  - Reduction of carbon dioxide by a diiron(I) complex gives mu-carbonato
      kappa(3)O:O',O''-bis{[2,2,6,6-tetramethyl-3,5-bis(2,4,6
      triisopropylphenyl)heptane-2,5-diiminate(1-)-kappa(2)N,N']iron(II)} toluene
      disolvate, [Fe(2)(C(41)H(65)N)(2)(CO(3))].2C(7)H(8), a diiron(II) species with a
      bridging carbonate ligand. The asymmetric unit contains one diiron complex and
      two cocrystallized toluene solvent molecules that are distributed over three
      sites, one with atoms in general positions and two in crystallographic 1 sites.
      Both Fe(II) atoms are eta(2)-coordinated to diketiminate ligands, but eta(1)- and
      eta(2)-coordinated to the bridging carbonate ligand. Thus, one Fe(II) center is
      three-coordinate and the other is four-coordinate. The bridging carbonate ligand
      is nearly perpendicular to the iron-diketiminate plane of the four-coordinate
      Fe(II) center and parallel to the plane of the three-coordinate Fe(II) center.

PMID- 19407404
TI  - The first example of a mixed alkoxide hydride of boron: sodium boron isopropoxide
      trihydride.
AB  - The title compound, poly[[mu-trihydro(isopropoxy)borato]sodium(I)],
      [Na(C(3)H(10)BO)](n), forms unique polymeric layers normal to the c axis via
      Na(+)...O [2.3405 (15) A] and Na(+)...H(borane) [2.22 (3) and 2.28 (3) A]
      interactions. This arrangement builds on distorted tetrahedral Na(+), oxygen and
      boron environments, with one of the borane hydride units uncoordinated, and
      highlights potential H(3)B-O-based chemistry.

PMID- 19407405
TI  - Dipyridinium dichromate: an achiral compound forming chiral crystals.
AB  - The title compound, (C(5)H(6)N)(2)[Cr(2)O(7)], crystallizes in one of the Sohncke
      space groups, viz. P2(1)2(1)2(1). Crystallization of dipyridinium dichromate is
      thus an example of spontaneous formation of a chiral crystal structure from
      achiral molecules. The dichromate anion adopts a virtually eclipsed achiral
      conformation, and the crystal structure is held together primarily by N-H...O and
      C-H...O interactions. The possibility of using dipyridinium dichromate as a
      reagent in enantioselective synthesis is discussed.

PMID- 19407406
TI  - The coordination polymers poly[mu-4,4'-bipyridyl-di-mu-formato-copper(II)] and
      catena-poly[[[diaqua(1-benzofuran-2,3-dicarboxylato)copper(II)]-mu-1,2-di-4
      pyridylethane] dihydrate].
AB  - The title compounds, [Cu(CHO(2))(2)(C(10)H(8)N(2))](n), (I), and
      {[Cu(C(10)H(4)O(5))(C(12)H(12)N(2))(H(2)O)(2)].2H(2)O}(n), (II), are composed of
      one-dimensional linear coordination polymers involving copper(II) ions and
      bidentate bipyridyl species. In (I), the polymeric chains are located on twofold
      rotation axes at (x, x, 0) and are arranged in layered zones centered at z = 0,
      1/4, 1/2 and 3/4 parallel to the ab plane of the tetragonal crystal. Weak
      coordination of the formate anions of one layer to the copper centers of
      neighboring layers imparts a three-dimensional connectivity to this structure. In
      (II), the polymeric chains propagate parallel to the a axis of the crystal.
      Noncoordinated water molecules link the chains through O-H...O hydrogen bonding
      in directions perpendicular to c, imparting to the entire structure three
      dimensional connectivity. The metal ions adopt distorted octahedral and square
      based pyramidal environments in (I) and (II), respectively. This study indicates
      that, under the given conditions, extended coordination involves Cu(II) centers
      associating with the bipyridyl ligands rather than with the competing
      benzofurandicarboxylate entities.

PMID- 19407408
TI  - Poly[[tetraaquatris(mu(3)-2,2-dimethylmalonato)dilanthanum(III)] monohydrate].
AB  - In the title complex, {[La(2)(C(5)H(6)O(4))(3)(H(2)O)(4)].H(2)O}(n), the La atoms
      are connected by bridging O atoms from carboxylate groups to build, through
      centres of inversion, two-dimensional layers parallel to the ac plane containing
      decanuclear 20-membered rings. The coordinated water molecules are involved in
      intralayer hydrogen-bond interactions. Adjacent layers are linked via hydrogen
      bonding to the solvent water molecules. This work represents the first example of
      a new substituted malonate-lanthanide complex.

PMID- 19407407
TI  - Nickel and zinc complexes with a monodentate heterocycle and tridentate Schiff
      base ligands: self-assembly to one- and two-dimensional supramolecular networks
      via hydrogen bonding.
AB  - In the complex (morpholine)[2-hydroxy-N'-(5-nitro-2
      oxidobenzylidene)benzohydrazidato]nickel(II),
      [Ni(C(14)H(9)N(3)O(5))(C(4)H(9)NO)], (I), the Ni(II) center is in a square-planar
      N(2)O(2) coordination geometry. The complex bis[mu-2-hydroxy-N'-(2
      oxidobenzylidene)benzohydrazidato]bis[(morpholine)zinc(II)],
      [Zn(2)(C(14)H(10)N(2)O(3))(2)(C(4)H(9)NO)(2)], (II), consists of a neutral
      centrosymmetric dimer with a coplanar Zn(2)(mu(2)-O)(2) core. The two Zn(II)
      centers are bridged by phenolate O atoms. Each Zn(II) center exhibits a distorted
      square-pyramidal stereochemistry, in which the four in-plane donors come from the
      O,N,O'-tridentate 2-hydroxy-N'-(2-oxidobenzylidene)benzohydrazidate(2-) ligand
      and a symmetry-related phenolate O atom, and the axial position is coordinated to
      the N atom from the morpholine molecule. There are intramolecular phenol
      hydrazide O-H...N hydrogen bonds present in both (I) and (II). In (I), square
      planar nickel complexes are linked by intermolecular morpholine-morpholine N
      H...O hydrogen bonds, leading to a one-dimensional chain, while in (II) an
      infinite two-dimensional network is formed via intermolecular hydrogen bonds
      between the coordinated morpholine NH groups and the uncoordinated phenolate O
      atoms.

PMID- 19407409
TI  - Bis(1,3,5-triazine-2,4,6-triamine-kappaN(1))silver(I) nitrate.
AB  - The title compound, [Ag(C(3)H(6)N(6))(2)]NO(3), has an alternating two
      dimensional bilayer structure supported by extensive hydrogen bonds. The
      [Ag(melamine)(2)](+) cationic monomers (melamine is 1,3,5-triazine-2,4,6
      triamine) are connected via N-H...N hydrogen bonds to form two-dimensional
      sheets. Nitrate groups are sandwiched between two sheets through N-H...O hydrogen
      bonds. An almost perfectly linear coordination geometry is found for the Ag(I)
      ions. The triazine ligands are slightly distorted due to pi-pi interactions.

PMID- 19407410
TI  - Linkage isomeric oxamate chelates: rac-bis(ethane-1,2-diamine)oxamatocobalt(III)
      bis(trifluoromethanesulfonate) dihydrate and Lambda(+)(578)-bis(ethane-1,2
      diamine)[oxamato(2-)]cobalt(III) trifluoromethanesulfonate.
AB  - The structures of rac-bis(ethane-1,2-diamine)(oxamato
      kappa(2)O(1),O(2))cobalt(III) bis(trifluoromethanesulfonate) dihydrate,
      [Co(C(2)H(2)NO(3))(C(2)H(8)N(2))(2)](CF(3)SO(3))(2).2H(2)O, (I), and
      Lambda(+)(578)-bis(ethane-1,2-diamine)[oxamato(2-)-kappa(2)N,O(1)]cobalt(III)
      trifluoromethanesulfonate, [Co(C(2)HNO(3))(C(2)H(8)N(2))(2)]CF(3)SO(3), (II), are
      compared. Together, the two complexes constitute the first pair of linkage
      isomers of bidentate oxamate available for structural comparison.

PMID- 19407411
TI  - Diphenyldipyridinezinc(II): partial spontaneous resolution of an organometallic
      reagent.
AB  - The title compound, [Zn(C(6)H(5))(2)(C(5)H(5)N)(2)], (I), forms conformationally
      chiral molecules residing on a twofold axis. The molecules are stacked along c,
      and these stacks are associated by edge-to-face pi-pi interactions. Crystals of
      (I) belong to the Sohncke space group P2(1)2(1)2 and the crystal lattice of (I)
      is chiral. The crystal batch that was examined consisted of a mixture of
      enantiomerically pure crystals and crystals twinned by inversion.

PMID- 19407412
TI  - Dimeric (isoquinoline)(N-salicylidene-D,L-glutamato)copper(II) ethanol solvate.
AB  - The title racemic complex, bis[mu-N-(2-oxidobenzylidene)-D,L-glutamato(2
      )]bis[(isoquinoline)copper(II)] ethanol disolvate,
      [Cu(2)(C(12)H(11)NO(5))(2)(C(9)H(7)N)(2)].2C(2)H(6)O, adopts a square-pyramidal
      Cu(II) coordination mode with a tridentate N-salicylideneglutamato Schiff base
      dianion and an isoquinoline ligand bound in the basal plane. The apex of the
      pyramid is occupied by a phenolic O atom from the adjacent chelate molecule at an
      apical distance of 2.487 (3) A, building a dimer located on the crystallographic
      inversion center. The Cu...Cu spacing within the dimers is 3.3264 (12) A. The
      ethanol solvent molecules are hydrogen bonded to the dimeric complex molecules,
      forming infinite chains in the a direction. The biological activity of the title
      complex has been studied.

PMID- 19407413
TI  - Products of the interaction of (1-diaminomethylene)thiourea with hydrofluoric
      acid.
AB  - The salts 1-(diaminomethylene)thiouron-1-ium hydrogen difluoride,
      C(2)H(7)N(4)S(+).HF(2)(-), (I), and bis[1-(diaminomethylene)thiouron-1-ium]
      hexafluoridosilicate, 2C(2)H(7)N(4)S(+).SiF(6)(2-), (II), have both been obtained
      from the reaction of (1-diaminomethylene)thiourea (HATU) with hydrofluoric acid.
      Both compounds contain extensive networks of N-H...F hydrogen bonds. The hydrogen
      difluoride salt contains four independent asymmetric [HF(2)](-) anions. In the
      hexafluoridosilicate salt, the centrosymmetric [SiF(6)](2-) anion is distorted,
      although this distortion is not clearly correlated with the N-H...F hydrogen
      bonding network.

PMID- 19407414
TI  - Hydrogen bonding and short contacts in [2,4,6
      tris(trifluoromethyl)phenyl]phosphinic acid.
AB  - In the title compound, C(9)H(4)F(9)O(2)P, molecules are linked by a single O
      H...O hydrogen bond into chains related to those in phenylphosphinic acid. There
      are short intramolecular F...P contacts.

PMID- 19407415
TI  - 5-(4,5-Ethylenedithio-1,3-dithiol-2-ylidene)-1,3,4,6-tetrathiapentalen-2-one
      (EDTO-TTP) and 5-[4,5-(ethene-1,2-diyldithio)-1,3-dithiol-2-ylidene]-1,3,4,6
      tetrathiapentalen-2-one (VDTO-TTP).
AB  - The title sulfur-rich organic molecular crystals, namely EDTO-TTP (C(9)H(4)OS(8))
      and VDTO-TTP (C(9)H(2)OS(8)), are characterized by conjugated C-S bonds and S...S
      intermolecular short contacts. The planar EDTO-TTP molecules are parallel packed
      and exhibit strong intermolecular interactions, including side-by-side transverse
      S...S contacts, face-to-face longitudinal pi-pi interactions and C-H...O hydrogen
      bonding. On cooling the EDTO-TTP crystal from 220 to 120 K, the cell dimensions
      and the intermolecular distances (such as S...S contacts and especially pi-pi
      spacings) become shorter, while the intramolecular bonds become longer. The
      curved VDTO-TTP molecules are packed in such a way as to make the crystal fully
      depolarized. The intermolecular interactions of the VDTO-TTP crystal are
      relatively weak, because of the weak pi-pi interactions and the lack of hydrogen
      bonding.

PMID- 19407416
TI  - Supramolecular hydrogen-bonded networks in adeninediium hemioxalate chloride and
      adeninium semioxalate hemi(oxalic acid) monohydrate.
AB  - In 9H-adenine-1,7-diium hemioxalate chloride, C(5)H(7)N(5)(2+).0.5C(2)O(4)(2
      ).Cl(-), (I), adenine is doubly protonated, while in 7H-adenin-1-ium semioxalate
      hemi(oxalic acid) monohydrate, C(5)H(6)N(5)(+).C(2)HO(4)(
      ).0.5C(2)H(2)O(4).H(2)O, (II), adenine and one oxalate anion are both
      monoprotonated. In (I), the adeninium cation forms R(2)(2)(8) and R(1)(2)(5)
      hydrogen-bonding motifs with the centrosymmetric oxalate anion, while in (II),
      the cation forms R(2)(1)(6) and R(1)(2)(5) motifs with the centrosymmetric oxalic
      acid molecule and R(1)(2)(5)and R(2)(2)(9) motifs with the monoprotonated oxalate
      anion. Linear hydrogen-bonded trimers are observed in (I) and (II). In both
      structures, the hydrogen bonds lead to the formation of two-dimensional
      supramolecular hydrogen-bonded sheets in the crystal packing. The significance of
      this study lies in the analysis of the interactions occurring via hydrogen bonds
      and the diversity seen in the supramolecular hydrogen-bonded networks as a result
      of such interactions.

PMID- 19407417
TI  - 4-Chloro-1-naphthol.
AB  - Molecules of the title compound, C(10)H(7)ClO, (I), are connected by a single
      strong O-H...O hydrogen bond into a simple C(2) chain, which runs parallel to the
      c axis and is additionally stabilized by intermolecular pi-pi stacking
      interactions. The significance of this study lies in the comparison drawn between
      the crystal structure of (I) and those of several of its simple analogues. This
      comparison shows a close similarity in the packing of the molecules that form pi
      stacks along the shortest crystallographic axes. A substantial spatial overlap is
      observed between adjacent molecules in such a pi-stack, depending mainly on the
      kind of substituent.

PMID- 19407418
TI  - Bis[4-(trimethylammonio)phenyl] disulfide diiodide acetone solvate.
AB  - The title compound, C(18)H(26)N(2)S(2)(2+).2I(-).2C(3)H(6)O, is an intermediate
      in the design of the zwitterionic thiolate 4-(trimethylammonio)benzenethiolate
      (Tab), in which a pair of aryl-substituted S atoms are linked by a covalent bond.
      The central S-S bond length is 2.020 (3) A and the C(ar)-S-S-C(ar) torsion angle
      is -84.1 (2) degrees . The crystal structure is stabilized by nonclassical
      hydrogen bonds which occur as intramolecular C-H...I interactions and
      intermolecular C-H...S and C-H...O contacts. In the crystal structure, both the
      dication and the two symmetrically independent iodide counter-anions are located
      on twofold crystallographic axes, whereas the acetone solvent molecule occupies a
      general position.

PMID- 19407419
TI  - 6beta-Hydroxy-5beta-methyl-20-oxo-19-norpregn-9(10)-en-3beta-yl acetate.
AB  - In the title compound, C(23)H(34)O(4), which is an intermediate in the synthesis
      of pregnane derivatives with a modified skeleton that show potent abortion
      inducing activity, the conformation of ring B is close to half-chair due to the
      presence of both the C=C double bond and the axial 5beta-methyl group. Rings A
      and C have conformations close to chair, while ring D has a twisted conformation
      around the bridgehead C-C bond. Molecules are hydrogen bonded via the hydroxyl
      and acetoxy groups into infinite chains. Quantum-mechanical ab initio Roothan
      Hartree-Fock calculations show that crystal packing might be responsible for the
      low values of the angles between rings A and B, and between ring A and rings C
      and D, as well as for a different steric position of the methyl ketone side chain
      compared to the geometry of the free molecule.

PMID- 19407420
TI  - A two-dimensional network in the molecular salt 2-methylimidazolium hydrogen
      glutarate, and three-dimensional networks in the salts 2-methylimidazolium
      hydrogen succinate and 2-methylimidazolium hydrogen adipate monohydrate.
AB  - All three title compounds, C(4)H(7)N(2)(+).C(4)H(5)O(4)(-), (I),
      C(4)H(7)N(2)(+).C(5)H(7)O(4)(-), (II), and C(4)H(7)N(2)(+).C(6)H(9)O(4)(-).H(2)O,
      (III), can be regarded as 1:1 organic salts. The dicarboxylic acids join through
      short acid bridges into infinite chains. Compound (I) crystallizes in the
      noncentrosymmetric Cmc2(1) space group and the asymmetric unit consists of a
      hydrogen succinate anion located on a mirror plane and a 2-methylimidazolium
      cation disordered across the same mirror. The other two compounds crystallize in
      the triclinic P1 space group. The carboxylic acid H atom in (II) is disordered
      over both ends of the anion and sits on inversion centres between adjacent
      anions, forming symmetric short O...H...O bridges. Two independent anions in
      (III) sit across inversion centres, again with the carboxylic acid H atom
      disordered in short O...H...O bridges. The molecules in all three compounds are
      linked into two-dimensional networks by combinations of imidazolium-carboxylate
      N(+)-H...O and carboxylate-carboxylate O-H...O hydrogen bonds. The two
      dimensional networks are further linked into three-dimensional networks by C
      H...O hydrogen bonds in (I) and by O(water)-H...O hydrogen bonds in (III).
      According to the DeltapK(a) rule, such 1:1 types of organic salts can be expected
      unambiguously. However, a 2:1 type of organic salt may be more easily obtained in
      (II) and (III) than in (I).

PMID- 19407421
TI  - Apparent shortening of the Csp(3)-Csp(3)bond analysed via a variable-temperature
      X-ray diffraction study in racemic 1,1'-binaphthalene-2,2'-diyl diethyl
      bis(carbonate).
AB  - Crystal structure determination at room temperature [292 (2) K] of racemic 1,1'
      binaphthalene-2,2'-diyl diethyl bis(carbonate), C(26)H(22)O(6), showed that one
      of the terminal carbon-carbon bond lengths is very short [Csp(3)-Csp(3) = 1.327
      (6) A]. The reason for such a short bond length has been analysed by collecting
      data sets on the same crystal at 393, 150 and 90 K. The values of the corrected
      bond lengths clearly suggest that the shortening is mainly due to positional
      disorder at two sites, with minor perturbations arising as a result of thermal
      vibrations. The positional disorder has been resolved in the analysis of the 90 K
      data following the changes in the unit-cell parameters for the data sets at 150
      and 90 K, which appear to be an artifact of a near centre of symmetry
      relationship between the two independent molecules in the space group P1 at these
      temperatures. Indeed, the unit cell at low temperature (150 and 90 K) is a
      supercell of the room-temperature unit cell.

PMID- 19407422
TI  - N,N'-dimethylpyrazinediium bis(tetrafluoroborate) and N,N'-diethylpyrazinediium
      bis(tetrafluoroborate): new examples of anion-pi triads.
AB  - Crystallization of N,N'-dimethylpyrazinediium bis(tetrafluoroborate),
      C(6)H(10)N(2)(2+).2BF(4)(-), (I), and N,N'-diethylpyrazinediium
      bis(tetrafluoroborate), C(8)H(14)N(2)(2+).2BF(4)(-), (II), from dried
      acetonitrile under argon protection has permitted their single-crystal studies.
      In both crystal structures, the pyrazinediium dications are located about an
      inversion center (located at the ring center) and each pyrazinediium aromatic
      ring is pi-bonded to two centrosymmetrically related BF(4)(-) anions. Strong
      anion-pi interactions, as well as weak C-H...F hydrogen bonds, between BF(4)(-)
      and pyrazinediium ions are present in both salts.

PMID- 19407424
TI  - Comparison of halogen bonding and van der Waals and pi-pi interactions in 4,5
      dibromo-2-hexyloxyphenol.
AB  - The title compound, C(12)H(16)BrO(2), is an interesting case of a simple organic
      molecule making use of five different types of intra- and intermolecular
      interactions (viz. conventional and nonconventional hydrogen bonds, and pi-pi,
      Br...Br and Br...O contacts), all of them relevant in the molecular and crystal
      structure geometry. The molecules are strictly planar, with an intramolecular O
      H...O hydrogen bond, and associate into two-dimensional structures parallel to
      (201) through two different types of halogen bonding. The planar structures, in
      turn, stack parallel to each other interlinked by C-H...pi and pi-pi contacts.
      Also discussed are the relevant structural features leading to the rather low
      melting point of the compound.

PMID- 19407423
TI  - 3-{[4-Amino-6-methoxy-2-(methylsulfanyl)pyrimidin-5-yl]amino}-1,2'-biindenylidene
      1',3'-dione dimethyl sulfoxide solvate: pi-stacked sheets of hydrogen-bonded
      chains of edge-fused rings.
AB  - In the title compound, C(24)H(18)N(4)O(3)S.C(2)H(6)OS, the biindenylidene
      component shows evidence of polarization of the electronic structure. The
      dimethyl sulfoxide solvent molecules are disordered over two sites, and they are
      linked to the biindenylidenedione components via N-H...O and C-H...O hydrogen
      bonds. A combination of N-H...N and N-H...O hydrogen bonds links the nonsolvent
      components into a chain of edge-fused centrosymmetric R(2)(2)(8) and R(2)(2)(22)
      rings, and these chains are linked into sheets by a single aromatic pi-pi
      stacking interaction.

PMID- 19407425
TI  - 5-Amino-2,4,6-tribromoisophthalic acid: the MAD triangle for experimental
      phasing.
AB  - The title compound, C(8)H(4)Br(3)NO(4), shows an extensive hydrogen-bond network.
      In the crystal structure, molecules are linked into chains by COO-H...O bonds,
      and pairs of chains are connected by additional COO-H...O bonds. This chain
      bundle shows stacking interactions and weak N-H...O hydrogen bonds with adjacent
      chain bundles. The three Br atoms present in the molecule form an equilateral
      triangle. This can be easily identified in the heavy-atom substructure when this
      compound is used as a heavy-atom derivative for experimental phasing of
      macromolecules. The title compound crystallizes as a nonmerohedral twin.

PMID- 19407426
TI  - 1,2,4,5-Tetrakis(diazidomethyl)benzene.
AB  - The molecule of the title compound, C(10)H(6)N(24), lies on a crystallographic
      inversion centre located in the middle of the benzene ring. Steric overcrowding
      by the bulky N(3) groups is avoided by the tendency of four azide entities to be
      arranged parallel to the benzene ring and the other four azide groups to be
      arranged alternately above and below the benzene plane in a skeletal C(i)
      symmetry. The compound is of interest for high-energy research and as a precursor
      for the synthesis of carbon nanotubes, nanospheres or high-nitrogen carbon
      nitrides with great potential for biological and technological applications.

PMID- 19407427
TI  - 3,3,4,4,5,5-Hexafluoro-1-(2-methoxyphenyl)-2-[5-(4-methoxyphenyl)-2-methyl-3
      thienyl]cyclopent-1-ene: a photochromic compound.
AB  - The photochromic title compound, C(24)H(18)F(6)O(2)S, has thienyl and aryl
      substituents on the C=C double bond of the shallow half-chair-shaped cyclopentene
      ring. The planes of the two substituent rings are inclined to that of the
      cyclopentene ring, with dihedral angles between the mean plane of the
      cyclopentene ring and those of the phenylene and thienyl rings of 51.2 (1) and
      51.3 (1) degrees, respectively. The molecule adopts an antiparallel conformation,
      with a distance between the two photoreactive C atoms of 3.717 (2) A.

PMID- 19407428
TI  - DL-cysteinium semioxalate.
AB  - Two chiral counterparts (L- and D-cysteinium cations related by an inversion
      centre) are present in the structure of the title compound,
      C(3)H(8)NO(2)S(+).C(2)HO(4)(-), with a 1:1 cation-anion ratio. The carboxy group
      of the cysteinium cation is protonated in the trans position relative to the
      amino group. The crystal structure is built up of double layers, in which dimers
      of cysteinium cations are connected to each other not directly, but via bridges
      of twisted semioxalate anions linked to each other via O-H...O hydrogen bonds
      forming infinite chains. An interesting feature of the crystal structure is the
      absence of either S-H...S or S-H...O hydrogen bonds.

PMID- 19407429
TI  - 1,3,5-Triphenyladamantane and 1,3,5,7-tetraphenyladamantane.
AB  - In 1,3,5-triphenyladamantane, C(28)H(28), (I), and 1,3,5,7-tetraphenyladamantane,
      C(34)H(32), (II), the molecules possess symmetries 3 and 4, and are situated
      across threefold and fourfold improper axes, respectively. The molecules
      aggregate by means of extensive C-H...pi interactions. In (I), the pyramidal
      shape of the molecules dictates the formation of dimers through a ;sixfold phenyl
      embrace' pattern. The dimers are linked to six close neighbors and constitute a
      primitive cubic net [H...pi = 2.95 (2) and 3.02 (2) A]. Compound (II) is
      isomorphous with tetraphenyl derivatives EPh(4) of group 14 (E = C-Pb) and ionic
      salts [EPh(4)][BPh(4)] (E = P, As and Sb). The multiple C-H...pi interactions
      arrange the molecules into chains, with a concerted action of CH (phenyl) and
      CH(2) (adamantane) groups as donors [H...pi = 3.15 (2) and 3.44 (2) A,
      respectively]. The additional interactions with the methylene groups (four per
      molecule) are presumably important for explaining the high melting point and
      insolubility of (II) compared with the EPh(4) analogs.

PMID- 19407430
TI  - Two isomeric cucurbitane derivatives.
AB  - Two isomeric cucurbitane derivatives, 3beta,7alpha,11beta-triacetoxycucurbit
      5(10)-ene, (I), and 3beta,7alpha,11beta-triacetoxy-5alpha-cucurbit-1(10)-ene,
      (II), both C(36)H(58)O(6), have their single endocyclic C=C double bonds in
      different positions. This results in differences in the conformation of the four
      ring system, which is close to a half-chair/half-chair/chair/half-chair
      arrangement in (I) and to a half-chair/twist-boat/boat/half-chair arrangement in
      (II). The orientation of some of the substituents is also different; the 3beta
      acetoxy group is in an equatorial position in (I) but in an axial position in
      (II), while the 11beta-acetoxy group occupies an axial position in (I) and an
      equatorial position in (II). The asymmetric unit of (I) contains two symmetry
      independent molecules which do not differ significantly, being related by a
      pseudo-twofold axis of symmetry. In both structures, the aliphatic chain
      fragments are disordered and the disorder persists at lower temperatures.

PMID- 19407431
TI  - The 2:1 salt-type adduct formed between 6-amino-3-methyl-5-nitrosopyrimidine
      2,4(1H,3H)-dione and piperidine: sheets containing 20 independent hydrogen bonds.
AB  - The title compound, piperidinium 6-amino-3-methyl-5-nitroso-2,4-dioxo-1,2,3,4
      tetrahydropyrimidin-1-ide 6-amino-3-methyl-5-nitrosopyrimidine-2,4(1H,3H)-dione,
      C(5)H(12)N(+).C(5)H(5)N(4)O(3)(-).C(5)H(6)N(4)O(3), (I), crystallizes with Z' = 2
      in the space group P1. There is an intramolecular N-H...O hydrogen bond in each
      pyrimidine unit and within the selected asymmetric unit the six independent
      components are linked by 11 hydrogen bonds, seven of the N-H...O type and four of
      the N-H...N type. These six-component aggregates are linked into sheets by five
      further hydrogen bonds, three of the N-H...O type and one each of the N-H...N and
      C-H...O types.

PMID- 19407432
TI  - Ultrastructural aspects of female aging Wistar rat epithelium tongue: a HRSEM and
      TEM study.
AB  - BACKGROUND: There is general consensus that the effects of intrinsic aging on the
      oral mucosa are relatively small, though potentially important to understanding
      the pathologies present in the aged animals. OBJECTIVE: In this paper, the
      development of dorsal surface of rat tongue was examined using transmission
      electron microscopy (TEM) and high-resolution scanning electron microscopy
      (HRSEM) in order to understand the age-related structural and ultrastructural
      changes experimentally. METHODS: In this study, we used female rats 75 and 720
      days old (adult and aging). Tissues of rat tongue were prepared and the specimens
      submitted to HRSEM and TEM techniques. RESULTS: The analysis of HRSEM and TEM
      demonstrated that the same characteristic keratinous epithelium was found in
      aging animals, however with some modifications. CONCLUSION: We agree that there
      are obvious changes in the oral mucosa with aging and these modifications can be
      observed starting from the ultrastructural aspects.

PMID- 19407433
TI  - Double Y-stent placement for tracheobronchial stenosis.
AB  - The silicone stent has been widely used to re-establish airway patency for
      patients with airway stenosis. The ideal shape of the stent should be well
      adapted to the tracheobronchial anatomic structures, and its optimal length
      should cover the entire inner wall of the stenotic airway. Although the silicone
      Y-stent was developed as a dedicated prosthesis for main carinal stenosis, we
      often encounter patients with tracheobronchial stenosis that cannot be treated by
      a single silicone Y-stent. The present study reports 2 cases of malignant disease
      who underwent double Y-stent placement on the involved carina between the right
      upper lobe bronchus and the bronchus intermedius as well as on the involved main
      carina as a unit. The procedure provided successful palliation.

PMID- 19407434
TI  - Cryptococcal pleuritis containing a high level of adenosine deaminase in a
      patient with AIDS: a case report.
AB  - Cryptococcal infection is the 4th most common opportunistic infection in patients
      with acquired immune deficiency syndrome (AIDS). Although pleural effusion alone
      is an unusual presentation, we present a case of cryptococcal pleuritis in an
      AIDS patient which was initially difficult to discriminate from tuberculous
      pleuritis because of the high level of pleural adenosine deaminase (ADA).
      Cryptococcus neoformans was detected in the culture of the pleural effusion after
      the initiation of antituberculous treatment. High levels of ADA in the pleural
      fluid can be observed in patients with cryptococcal pleuritis, and longer
      incubation of pleural fluid should be performed in all patients who present with
      pleuritis associated with a high ADA level as the only significant finding.

PMID- 19407436
TI  - St. Agnes of Rome: patron saint for women with hair loss?

PMID- 19407435
TI  - Seasonality of hair shedding in healthy women complaining of hair loss.
AB  - BACKGROUND: A number of otherwise healthy women with or without clinical alopecia
      complain of recurrent hair loss, presumably reflecting seasonality in the growth
      and shedding of hair. OBJECTIVE: To test the hypothesis that periodicity in hair
      shedding reflects seasonal changes in human hair growth. METHODS: Retrospective
      case study over a period of 6 years of apparently healthy women with the
      complaint of hair loss. All underwent biochemical investigations, and trichograms
      were made. RESULTS: After exclusion of patients with a disease or on drugs known
      to cause hair loss, 823 women remained. Analysis of trichograms demonstrated
      annual periodicity in the growth and shedding of hair, manifested by a maximal
      proportion of telogen hairs in summer. A second peak seems to exist, though it is
      less pronounced, in spring. The telogen rates were lowest in late winter.
      CONCLUSIONS: These results confirm the findings of former authors who have
      indicated seasonal changes in human hair growth, though this is the first study
      performed systematically in a representative number of women.

PMID- 19407437
TI  - Partial reconstitution of cutaneous microvessels in long-term survivors after
      allogeneic bone marrow transplantation.
AB  - BACKGROUND: Graft-versus-host disease (GVHD) is a major complication after
      allogeneic hematopoietic stem cell transplantation (HSCT) and skin is involved in
      acute and chronic disease. Immune-mediated vessel attack and subsequent
      microvessel loss have been observed in skin of patients with chronic GVHD.
      OBJECTIVES: To test whether long-term survivors (LTS) after allogeneic HSCT
      without cutaneous GVHD show signs of persistent vascular remodeling. METHODS:
      Microvessels in skin biopsies were investigated in a cohort of 32 LTS with a
      median follow-up of 17 years (range 11-26). Five were currently classified as
      having chronic GVHD other than skin involvement. RESULTS: LTS showed no
      significant difference in median microvessel density and relative vessel size
      distribution pattern compared to healthy controls. Past experience of GVHD and
      current status of chronic GVHD other than skin involvement had no impact on
      vessel density. In contrast, recipients with chronic cutaneous GVHD of sclerotic
      type and patients with lichen sclerosus have significant microvessel loss in the
      upper dermis. CONCLUSION: The complex therapy of allogeneic HSCT had no sustained
      effect on the microvascular architecture of LTS when clinicopathological evidence
      of cutaneous GVHD is absent. Microvascular remodeling as observed during chronic
      GVHD recovers completely after resolution of chronic cutaneous GVHD.

PMID- 19407438
TI  - Functional reserve before lung resection: how low can we go?

PMID- 19407439
TI  - The management of Gaucher disease in developing countries: a successful
      experience in Southern Brazil.
AB  - OBJECTIVE: Gaucher disease (GD) is a genetic disease caused by glucocerebrosidase
      deficiency. GD is treated by enzyme replacement therapy (ERT) with imiglucerase,
      a high-cost drug provided by the Brazilian Ministry of Health (BMH). This study
      reports the implementation of the BMH guidelines for GD in the southernmost state
      of the country. METHODS: We review the clinical and laboratorial data for
      patients seen at the reference center for GD from Rio Grande do Sul, Brazil (July
      2003 to June 2006). RESULTS: Twenty-five patients were included in this study. At
      baseline, 19/20 were on ERT (mean dosage of imiglucerase = 51.8 U/kg/infusion),
      3/17 presented anemia, and 5/16 thrombocytopenia. The amount of imiglucerase
      prescribed to these patients was adjusted according to the guidelines in July
      2003; out of them, 18 were receiving ERT in the reference center at month 36
      (mean dosage of imiglucerase = 27.5 U/kg/infusion), 2/18 presented anemia, and
      4/18 presented thrombocytopenia. The analysis of the liver, spleen, and bone data
      presented some limitations, but the available information suggests that patients
      did not deteriorate. GD patients who initiated ERT after July 2003 (n = 5)
      received lower dosage of imiglucerase since the beginning of the treatment; most
      of them demonstrated clinical and laboratorial response. From baseline to month
      36, the consumption of imiglucerase by the reference center showed a significant
      reduction, which represented savings of USD 3 million to the public health
      system. CONCLUSIONS: The model of care of GD patients suggested by the BMH
      guidelines appears to be cost-effective and could be an example for management of
      rare diseases in underdeveloped countries.

PMID- 19407440
TI  - Psychological and behavioral responses to genetic test results indicating
      increased risk of obesity: does the causal pathway from gene to obesity matter?.
AB  - BACKGROUND: Common obesity-associated genetic variants may exert their effects
      through increasing eating or decreasing metabolism. Such differences might
      influence individual responses to obesity genetic test results. METHODS: This was
      an experimental analogue study: 191 participants were asked to imagine they had
      received a genetic test result indicating high eating-based (n = 37) or high
      metabolism-based (n = 41) risk of obesity, an enzyme test result indicating high
      eating-based (n = 35) or high metabolism-based (n = 41) risk of obesity, or no
      risk information (n = 37). Outcomes included perceived risk, self-efficacy
      (confidence in ability to eat healthily), response-efficacy (confidence that
      eating healthily will reduce risk), and intention to eat healthily. RESULTS: The
      groups receiving increased obesity risk information reported greater perceived
      risk and intention to eat healthily than the no risk information group (both p <
      0.01). There were main effects of test type on perceived risk (genetic vs.
      enzyme: 3.91 vs. 3.55, p = 0.031) and of causal pathway on worry (eating vs.
      metabolism: 3.33 vs. 2.86, p = 0.049), but no effects of either manipulation on
      any other outcomes. CONCLUSION: Personal risk information indicating increased
      obesity risk may increase motivation to eat healthily, regardless of whether the
      risk is described as genetic or non-genetic or as acting through an eating-based
      or metabolism-based causal pathway.

PMID- 19407441
TI  - Factors influencing uptake of pharmacogenetic testing in a diverse patient
      population.
AB  - BACKGROUND: The successful integration of pharmacogenetic (PGx) testing into
      clinical care will require attention to patient attitudes. In this study, we
      aimed to identify the major reasons why patients would or would not consider PGx
      testing and whether these factors differed by race, socioeconomic and insurance
      status, and medical history. METHODS: We developed and conducted a survey within
      the adult patient population of the Duke Family Medicine Center. RESULTS: Of 75
      completed surveys (65% African-American), 77% indicated they were 'very likely'
      or 'somewhat likely' to take a PGx test. Respondents who had experienced a side
      effect were significantly more likely to indicate they would take a PGx test and
      expressed greater interest in learning more about testing than those who had not.
      Drug safety and effectiveness were the major reasons to have PGx testing. Privacy
      concerns and lack of insurance coverage for testing were the major reasons to
      decline testing. CONCLUSIONS: We found no differences in interest in PGx tests by
      race or socioeconomic status, but found stronger interest from those with a
      history of side effects and private insurance. While the overall support of PGx
      testing is encouraging, greater reassurance of medical privacy and development of
      educational resources are needed.

PMID- 19407442
TI  - Renal allograft calcification -- prevalence and etiology in pediatric patients.
AB  - BACKGROUND: Calcification of renal allografts has been reported in adult kidney
      transplant (KTx) recipients with a widely differing prevalence (2-60%).
      Persistent hyperparathyroidism, hypercalcemia and concomitant hypercalciuria were
      identified as major risk factors. We aimed to determine the prevalence and risk
      factors for such calcifications in children. METHODS: We investigated
      histological stains of routine graft biopsies from pediatric KTx patients for
      renal calcifications and determined the urinary excretion of lithogenic (oxalate,
      calcium) and stone-inhibitory substances (citrate). RESULTS: In our series of
      transplant patients, tubular calcification was found in 16 of the 36 (44.4%) KTx
      biopsies by an additional Kossa stain. This transplant calcification was not
      associated with any singular risk factor and was not correlated to a worse
      transplant outcome. CONCLUSION: Although our pediatric findings confirm the
      reported incidence rates of KTx calcification in adults, we could neither
      identify hypercalciuria as a risk factor nor confirm any negative influence on
      graft function. However, long-term studies are clearly needed to prove or
      disprove a negative impact of calcifications on graft function.

PMID- 19407443
TI  - Pre-eclampsia is a risk factor of carotid artery atherosclerosis.
AB  - BACKGROUND: A history of pre-eclampsia has been shown to be associated with an
      increased risk of subsequent coronary artery disease. The intima-media thickness
      of carotid arteries and the detection of plaques are useful measures as regards
      preclinical atherosclerosis. The aim of this study was to examine whether women
      with a history of pre-eclampsia more often show signs of atherosclerosis compared
      with 2 control groups. METHODS: We used data from a large Finnish cross-sectional
      health examination survey. We had women with previous pre-eclampsia (n = 35) or
      pregnancy-induced hypertension (n = 61) and 2 control groups. Laboratory tests
      and physical examination were performed. Information on reproductive and medical
      history was obtained at the home interview. Carotid atherosclerosis was assessed
      by ultrasonography. RESULTS: The women with previous pre-eclampsia had
      significantly (p = 0.008) more atherosclerotic plaques than the healthy parous
      controls. The intima-media thickness in the women with previous pre-eclampsia
      also tended to be higher than in the other groups, although the differences did
      not reach statistical significance. In logistic regression analysis, advanced age
      (OR: 1.08; 95% CI: 1.04-1.13; p < 0.001) and pre-eclampsia (OR: 3.63; 95% CI:
      1.50-8.79; p = 0.004) were independent risk factors as regards plaque, and in
      linear regression analysis advanced age (estimate: 0.012; 95% CI: 0.010-0.014; p
      < 0.001), HDL cholesterol (estimate: -0.049; 95% CI: -0.088 to -0.010; p =
      0.013), systolic blood pressure, BMI (estimate: 0.005; 95% CI: 0.000-0.009; p =
      0.043) and high-sensitivity C-reactive protein (estimate: -0.003; 95% CI: -0.007
      to -0.000; p = 0.048) were independent risk factors with respect to intima-media
      thickness. CONCLUSIONS: Our data suggest that pre-eclampsia is an independent
      risk factor as regards developing plaque later in life.

PMID- 19407444
TI  - The Prevention of cerebrovascular and cardiovascular Events of ischemic origin
      with teRutroban in patients with a history oF ischemic strOke or tRansient
      ischeMic attack (PERFORM) study: baseline characteristics of the population.
AB  - BACKGROUND: The Prevention of cerebrovascular and cardiovascular Events of
      ischemic origin with teRutroban in patients with a history oF ischemic strOke or
      tRansient ischeMic attack (PERFORM) study is an international double-blind,
      randomized controlled trial designed to investigate the superiority of the
      specific TP receptor antagonist terutroban (30 mg/day) over aspirin (100 mg/day),
      in reducing cerebrovascular and cardiovascular events in patients with a recent
      history of ischemic stroke or transient ischemic attack. Here we describe the
      baseline characteristics of the population. METHODS AND RESULTS: Parameters
      recorded at baseline included vital signs, risk factors, medical history, and
      concomitant treatments, as well as stroke subtype, stroke-associated disability
      on the modified Rankin scale, and scores on scales for cognitive function and
      dependency. Eight hundred and two centers in 46 countries recruited a total of
      19,119 patients between February 2006 and April 2008. The population is evenly
      distributed and is not dominated by any one country or region. The mean +/- SD
      age was 67.2 +/- 7.9 years, 63% were male, and 83% Caucasian; 83% had
      hypertension, and about half the population smoked or had quit smoking. Ninety
      percent of the qualifying events were ischemic stroke, 67% of which were
      classified as atherothrombotic or likely atherothrombotic (pure or coexisting
      with another cause). Modified Rankin scale scores showed slight or no disability
      in 83% of the population, while the scores on the Mini-Mental State Examination,
      Isaacs' Set Test, Zazzo's Cancellation Test, and the instrumental activities of
      daily living scale showed a good level of cognitive function and autonomy.
      CONCLUSIONS: The PERFORM study population is homogeneous in terms of demographic
      and disease characteristics. With 19,119 patients, the PERFORM study is powered
      to test the superiority of terutroban over aspirin in the secondary prevention of
      cerebrovascular and cardiovascular events in patients with a recent history of
      ischemic stroke or transient ischemic attack.

PMID- 19407445
TI  - 6,7-dihydroxy-3,4-dihydroisoquinoline: a novel inhibitor of nuclear factor-kappaB
      and in vitro invasion in murine mammary cancer cells.
AB  - BACKGROUND: The inhibition of nuclear factor (NF)-kappaB with nontoxic agents is
      a promising possible treatment approach that may inhibit tumor cell
      proliferation, counteract the prosurvival pathways that mediate resistance to
      cytotoxic therapy, and prevent tumor cell metastasis. METHODS: An initial
      structure-activity relationship study of the NF-kappaB inhibitory activity of
      acetophenone-type compounds using electrophoretic mobility shift assay and
      Western blot analysis is presented. An in vitro cell invasion assay using DA3
      cells, a murine breast cancer cell line, was conducted to model antimetastatic
      activity. RESULTS: The carbonyl moiety is found to be the functional group
      responsible for inhibition of NF-kappaB, and a novel, more effective agent, 6,7
      dihydroxy-3,4-dihydroisoquinoline, is postulated and confirmed. The compounds are
      characterized as active in the inhibition of both the canonical and noncanonical
      NF-kappaB signaling pathways. Lastly, 6,7-dihydroxy-3,4-dihydroisoquinoline is
      discovered to inhibit in vitro invasion in DA3 cells. CONCLUSION: 6,7-Dihydroxy
      3,4-dihydroisoquionoline and its derivatives are presented as potential
      prototypes for a novel series of nontoxic antimetastatic agents that can be used
      in conjunction with current cancer therapeutic techniques.

PMID- 19407446
TI  - Increased uptake and improved intracellular survival of a teicoplanin-resistant
      mutant of methicillin-resistant Staphylococcus aureus in non-professional
      phagocytes.
AB  - BACKGROUND/AIMS: Endogenous development of glycopeptide-intermediate resistance
      is linked to multiple genetic and phenotypic changes in clinical and laboratory
      isolates of Staphylococcus aureus. This study evaluated endocytic uptake and
      intracellular survival of a teicoplanin-resistant derivative of S. aureus in a
      human epithelial cell line, and compared these to the isogenic teicoplanin
      susceptible parent or a spontaneously derived, susceptible revertant. METHODS:
      Endocytic uptake of teicoplanin-resistant and teicoplanin-susceptible strains by
      human embryonic kidney 293 cells was estimated by a lysostaphin protection assay.
      Differential intracellular survival of all S. aureus strains from 2 to 24 h was
      evaluated by colony-forming unit counts of Triton X-100-lysed 293 cells,
      following lysostaphin inactivation. RESULTS: Endocytic uptake of the teicoplanin
      resistant strain increased by approximately 4-fold over its teicoplanin
      susceptible counterparts. Furthermore, the teicoplanin-resistant strain showed an
      11-fold increase in intracellular colony-forming unit counts from 2 to 24 h,
      compared to its teicoplanin-susceptible counterparts that showed marginal (<2
      fold) changes during the same time period. Infected host cells showed no
      significant viability loss at 24 h, as assessed by Trypan blue dye exclusion.
      CONCLUSIONS: Intracellular location might confer a significant fitness benefit to
      glycopeptide-intermediate isolates of methicillin-resistant S. aureus and further
      protect them from cell wall-active antibiotics whose intracellular activity is
      limited.

PMID- 19407447
TI  - Colonic ulcers in a patient taking low-dose aspirin.

PMID- 19407448
TI  - Accuracy of computed tomographic colonography for the detection of polyps and
      colorectal tumors: a systematic review and meta-analysis.
AB  - BACKGROUND: The real accuracy of computed tomographic colonography (CTC) is still
      unknown. OBJECTIVE: To perform a meta-analysis of the diagnostic accuracy of CTC
      for the detection of polyps and colorectal tumors. METHODS:  SELECTION OF
      STUDIES: Studiesassessing the accuracy of CTC for the detection of colorectal
      polyps and tumors were selected. data synthesis: Meta-analyses combining
      sensitivities, specificities and likelihood ratios (LRs) for the diagnosis of
      polyps and colorectal tumors were carried out. RESULTS: Forty-seven studies,
      providing data of 10,546 patients, were included. Overall per-polyp sensitivity
      of CTC was 66% (64-68%), for polyps 6-9 mm in size it was 59% (56-61%), and 76%
      (73-79%) for polyps larger than 9 mm. Overall per-patient sensitivity was 69% (66
      72%), for polyps 6-9 mm 60% (56-65%), and 83% (70-85%) for lesions larger than 9
      mm. Overall CTC specificity was 83% (81-84%). Positive and negative LRs were 2.9
      (1.8-4) and 0.38 (0.27-0.53), respectively; for polyps 6-9 mm in size, they were
      3.8 (2.5-5.7) and 0.4 (0.27-0.59), and 12.3 (7.7-19.4) and 0.19 (0.12-0.3) for
      polyps larger than 9 mm. CONCLUSION: CTC is highly specific for the detection of
      colorectal polyps and tumors. Some studies reported high sensitivities, but the
      results of the studies were highly heterogeneous, while the studied variables
      explained only part of this discrepancy.

PMID- 19407449
TI  - Levodopa: past, present, and future.
AB  - Levodopa has been the mainstay of treatment for Parkinson's disease (PD) for more
      than 40 years. During this time, researchers have strived to optimize levodopa
      formulations to minimize side effects, enhance central nervous system (CNS)
      bioavailability, and achieve stable therapeutic plasma levels. Current strategies
      include concomitant treatment with inhibitors of dopa decarboxylase (DDC) and
      catechol-O-methyltransferase (COMT) to prolong the peripheral levodopa half-life
      and increase CNS bioavailability. Levodopa combined with DDC inhibition is the
      current standard method of delivering levodopa for symptomatic treatment of PD.
      Recent research suggests that continuous dopaminergic stimulation that more
      closely approximates physiological stimulation may delay or prevent the
      development of motor fluctuations ('wearing off') and dyskinesias. Strategies
      currently being used to achieve more continuous dopaminergic stimulation include
      the combination of an oral levodopa/DDC inhibitor with a COMT inhibitor and the
      enteral infusion of a levodopa gel formulation. Attempts are underway to develop
      oral and transdermal very long-acting levodopa preparations.

PMID- 19407450
TI  - Clinical, biochemical and neuroimaging parameters after thrombolytic therapy
      predict long-term stroke outcome.
AB  - INTRODUCTION: We investigated the predictive value of standard neurological
      evaluation, a commercially available biomarker assay and neuroimaging in the
      subacute phase for outcome after thrombolytic therapy in ischemic stroke.
      METHODS: Thirty-four consecutive ischemic stroke patients were evaluated by means
      of the NIH Stroke Scale (NIHSS(72)), the Triage(R) Stroke Panel (MMX(72)) and
      standardized infarct volumetry at 72 h after treatment with intravenous
      recombinant tissue plasminogen activator or intra-arterial urokinase. Outcome was
      assessed by the modified Rankin Scale (mRS) at 3 months after the stroke.
      RESULTS: NIHSS(72), MMX(72) and infarct volume correlated significantly with the
      mRS score at month 3 and emerged as independent outcome predictors from logistic
      regression analysis. NIHSS(72) is the best predictor for outcome, but its
      accuracy increases by 9 and 6% when combined with MMX(72) and infarct volumetry,
      respectively. The combined use of NIHSS(72) and MMX(72) allows long-term outcome
      prediction with 97% accuracy, which is not further improved by infarct volumetry.
      CONCLUSIONS: Routine clinical evaluation, bedside testing of biochemical markers
      by the Triage Stroke Panel and infarct volumetry on neuroimaging at 72 h after
      thrombolytic therapy are predictors for long-term outcome of ischemic stroke
      patients. Clinical assessment is the most reliable parameter for outcome
      prediction, but its predictive value is substantially improved when combined with
      the biomarker panel.

PMID- 19407451
TI  - Primary diffuse leptomeningeal gliomatosis.
AB  - BACKGROUND: Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare
      presentation of a primary central nervous system glial tumor. METHODS: Four case
      reports of PDLG in young males aged 14-24 years are presented. These reports are
      discussed in the context of the existing literature. RESULTS: The clinical
      presentation of 4 new cases of PDLG resembled chronic meningitis with and without
      polyradiculopathy. Spinal fluid studies are typically nondiagnostic, but
      characteristically show elevated opening pressure, an elevated protein level, and
      a relative paucity of cellular reaction. An accurate antemortem diagnosis
      required contrast-enhanced imaging and meningeal biopsy in all 4 of our cases.
      Treatment strategies including craniospinal radiation and chemotherapeutic
      approaches, alone or in combination, have not been proven to alter the course of
      the disease. Initial responses to temozolomide and radiation treatments in all 4
      of our cases were promising, resulting in temporary stabilization of the disease
      and prolonging life expectancy over what was previously reported in the
      literature. CONCLUSION: Total neuroaxis contrast-enhanced MRI scanning is
      required for directing biopsy confirmation and detecting the extent of the
      disease. More effective therapeutic strategies are needed, but the combination of
      temozolomide and radiation therapy may slow disease progression.

PMID- 19407452
TI  - Sleep and vigilance disorders in pregnancy.
AB  - OBJECTIVES: To describe different sleep disorders and daytime sleepiness in a
      French population of randomly selected young women during pregnancy and to
      evaluate the frequency of these sleep disorders according to the three trimesters
      of pregnancy. METHODS: Cross-sectional design with retrospective survey of pre
      pregnancy, symptoms and prospective survey of current symptoms. Mothers were
      interviewed during pregnancy with a questionnaire to evaluate their sleep before
      pregnancy and to assess alterations in their sleep according to the trimester.
      RESULTS: 871 pregnant women completed the questionnaire. The rate of pregnant
      women with insomnia with non-refreshing sleep and frequent awakenings increases
      during the second and the third trimester reaching more than 75% of the women,
      essentially due to an urge to urinate, movements of the fetus, backache and
      restless legs syndrome. Snoring also increases throughout the pregnancy with more
      than 18% of them snoring every night. Conversely, more than 75% of the women
      complained of a decrease in their vigilance and a need to nap inreased during the
      pregnancy. CONCLUSIONS: The subjective quality of sleep is disturbed as early as
      the first trimester of pregnancy and increases throughout the pregnancy, except
      for excessive daytime sleepiness which was more frequent during the first
      trimester.

PMID- 19407453
TI  - Increased expression of cell-cell signaling genes by stimulated mononuclear
      leukocytes in patients with previous atherothrombotic stroke. A whole genome
      expression profile study.
AB  - BACKGROUND/AIMS: Inflammation plays an important role in atherosclerosis and
      stroke. Acute infections are recognized as trigger factors for ischemic stroke.
      METHODS: In this whole genome expression profile study of 15 patients and 15
      control subjects, we tested the hypothesis that patients with a history of
      atherothrombotic stroke show enhanced transcription of inflammatory genes in
      circulating leukocytes. RNA from unstimulated or lipopolysaccharide (LPS)
      stimulated peripheral blood mononuclear cells (PBMCs) was analyzed with
      Affymetrix U133A GeneChips using a pooling design. Expression of single genes and
      functional groups of genes was analyzed by global statistical tests. RESULTS: A
      total of 10,197 probe sets showed positive calls. After correction for multiple
      testing no single probe set revealed significant differences either without or
      with LPS stimulation. However, significant global expression differences were
      found upon LPS stimulation for the group of genes that are involved in cell-cell
      signaling. CONCLUSION: LPS stimulation of PBMCs, a condition mimicking bacterial
      infection, induces differential expression of a group of cell-cell signaling
      genes in patients with previous atherothrombotic stroke. This finding can be
      caused by genetic differences between both groups, but acquired risk factors,
      medication and technical factors may also have contributed to the result.

PMID- 19407455
TI  - Cognitive dysfunction in systemic lupus erythematosus: prevalence and correlates.
AB  - Little is known about the mechanisms and relevance of cognitive dysfunction in
      systemic lupus erythematosus (SLE) patients who never displayed major
      neuropsychiatric manifestations (nSLE). Thirty-one nSLE female patients and 31
      cognitively healthy control women were recruited. Sociodemographic, clinical,
      neuropsychological and SLE-related markers were collected including cerebral
      perfusion by single-photon emission computed tomography. Prevalences of cognitive
      complaints were 22.6% in nSLE versus 6.5% in the control group (p = 0.147);
      respective prevalences of cognitive dysfunction were 32.3 versus 6.5% (p = 0.01).
      Within the nSLE group, all cognitive domains appeared similarly affected, and
      correlations were found between cognitive dysfunction and less skilled occupation
      (r = -0.41, p = 0.02) and between cognitive complaints and depressive symptoms (r
      = 0.35, p = 0.05). Cognitive dysfunction is rather frequent in nSLE and seems to
      negatively impinge on social functioning.

PMID- 19407454
TI  - Safety and tolerability of pardoprunox, a new partial dopamine agonist, in a
      randomized, controlled study of patients with advanced Parkinson's disease.
AB  - AIMS: To investigate the safety and tolerability of pardoprunox (SLV308), a novel
      partial dopamine agonist, as an adjunct to levodopa in patients with advanced
      Parkinson's disease, using two titration schedules. METHODS: Patients were
      randomized to pardoprunox (n = 51) or placebo (n = 11). Pardoprunox was titrated
      to the highest tolerated dose (range, 0.3-42 mg/day) over 7 weeks, using a
      gradual dose escalation without intermediate steps (group 1) or with intermediate
      steps (group 2). RESULTS: The cumulative drop-out rate was greater in group 1
      (without intermediate steps, 56.0%) than in group 2 (with intermediate steps,
      34.6%), or with placebo (9.1%). In group 2, doses up to 18 mg/day were well
      tolerated with a cumulative drop-out rate of 7.7% (2/26) and a drop-out rate due
      to adverse events of 4.0% (1/26). The most common adverse events reported were
      nausea, vomiting, headache, and dizziness. There was a trend for reduced OFF time
      (p = 0.054) in the combined pardoprunox group compared to placebo. CONCLUSIONS:
      The pardoprunox safety and tolerability profile as an adjunct to levodopa was
      improved using a gradual titration schedule that included intermediate dose
      steps. Using this titration, doses up to 18 mg/day were well tolerated.

PMID- 19407456
TI  - Thirty neurological eponyms associated with the nazi era.
AB  - In the 1920s, the neurosciences in Germany were world-class. Then came Hitler's
      regime, and with it 2 distinct changes happened to the research milieus in Berlin
      and elsewhere. First, the persecution of Jews and others deprived Germany of many
      of its most outstanding scientists. Second, numerous German and Austrian
      physicians became active in National Socialist (NS)-euthanasia programs. In
      recent years, the medical community has become more aware of the ethical burden
      associated with eponyms derived from scientists of the Third Reich. Yet a list of
      these eponyms with emphasis on clinical neurology is still missing. This paper
      therefore reviews 30 neurological eponyms derived from 29 physicians who lived in
      the Nazi era. Among them are victims who were forced out of the country or
      murdered in concentration camps, protestors who risked their academic careers and
      often their lives, beneficiaries who published on brains from 'euthanized'
      children, and collaborators who were directly involved in the planning and
      execution of NS-euthanasia programs.

PMID- 19407457
TI  - Schneckenbecken dysplasia in fetus: report of four cases.
AB  - Several different types of lethal short-limbed skeletal dysplasia with
      platyspondylia have been recognized with a different mode of inheritance.
      Schneckenbecken dysplasia, a very rare lethal osteochondrodysplasia, is included
      in these entities, with an autosomal recessive mode of inheritance. We describe 4
      new Tunisian cases with clinical, radiographic and histopathological features.
      The fetuses were of consanguineous parents. Prenatal diagnostics of short limbs
      were carried out on ultrasounds at 20, 22, 23 and 28 weeks of gestation. The
      radiographic findings were typical, showing especially the small ilia with medial
      snail-like projection. The chondro-osseous histology of the 4 cases was
      compatible with the diagnostics demonstrating cartilage anomalies characterized
      by hypercellularity, hypervascularisation and chondrocytes with central large
      round nucleus. Schneckenbecken dysplasia should be considered when the phenotype
      of dwarfism and snail feature of iliac bone associated with histological finding
      are presented. Frozen fetal samples should be taken in order to look for
      candidate genes.

PMID- 19407458
TI  - Incidence of overactive bladder after vaginal hysterectomy and associated repairs
      for pelvic organ prolapse.
AB  - OBJECTIVE: The aim of this study was to determine the incidence of overactive
      bladder (OAB) after vaginal hysterectomy for pelvic organ prolapse (POP) and
      analyze the associated risk factors. STUDY DESIGN: This was a retrospective
      cohort study of 217 patients who underwent primary POP vaginal surgery between
      the years 2000 and 2004 in Donostia Hospital and who did not report OAB before
      surgery. A personal interview was undertaken after surgery for the diagnosis of
      OAB, taking into account the ICS 2002 definition. Descriptive statistical
      analyses and multivariate logistic regression were performed to determine the
      factors associated with the development of OAB after POP surgery. RESULTS: De
      novo OAB was diagnosed in 43 (19.8%) patients. The median time at onset of OAB
      symptoms after surgery was 3 months. Urge urinary incontinence was present in 28
      patients (12.9%). Those women operated on also for stress urinary incontinence
      were at an increased risk for de novo OAB. CONCLUSION: Nearly 20% of women
      operated on for POP develop OAB soon after surgery. Those operated on for POP and
      stress urinary incontinence are more at risk.

PMID- 19407459
TI  - Association between aldosterone synthase CYP11B2 polymorphism and essential
      hypertension in Chinese: a meta-analysis.
AB  - A thymidine-to-cytosine substitution in the -344 promoter region of the
      aldosterone synthase gene (CYP11B2) has been associated with essential
      hypertension in some but not all studies conducted in Chinese. We performed a
      meta-analysis to evaluate the association of the -344C/T polymorphism with
      essential hypertension in Chinese. A total of 7,472 individuals (4,259 unselected
      hypertensive patients and 3,213 normotensive controls) from 9 case-control
      studies were included in the present investigation. Significant associations
      between the risk of hypertension and the CC genotype and C allele frequencies
      were found in a total of 19 studies. Our findings support the notion that the
      CYP11B2 -344C/T polymorphism is associated with essential hypertension. In
      addition, C allele frequency was found to be lower in southern Chinese controls
      than in their northern counterparts, and the higher TT genotype homozygous
      frequency in the southern Chinese supports the hypothesis that the northern
      Chinese are of southern origin.

PMID- 19407460
TI  - Association between changes in obesity parameters and incidence of chronic kidney
      disease in Japanese individuals.
AB  - Obesity increases the risk for chronic kidney disease (CKD). By analyzing data on
      individuals who underwent general health screening in two consecutive years, we
      investigated whether changes in body mass index (BMI) or waist circumference (WC)
      were associated with the appearance or disappearance of the CKD components; micro
      /macroalbuminuria (> or =30 mg urinary albumin per gram creatinine) and a low
      estimated glomerular filtration rate (eGFR; <60 ml/min/1.73 m(2)). Logistic
      regression analysis showed that in men with micro-/macroalbuminuria at the first
      visit, a BMI reduction of > or =0.42 or a WC reduction of > or =3.0 cm over the 1
      year period resulted in a significantly reduced incident of micro
      /macroalbuminuria at the second visit. On the other hand, a BMI gain of > or
      =0.33 over 1 year in men without micro-/macroalbuminuria and a low eGFR at the
      fist visit significantly increased the incident of micro-/macroalbuminuria and a
      low eGFR, respectively, at the second visit. These findings indicate that
      lowering the obesity indexes in men with micro-/macroalbuminuria reduced the
      incidence of this condition at the 1-year follow-up and that, on the contrary, an
      increase in BMI in men without micro-/macroalbuminuria and a low eGFR at the
      first examination increased the risk of these conditions during the 1-year follow
      up period.

PMID- 19407461
TI  - Using telephone and informant assessments to estimate missing Modified Mini
      Mental State Exam scores and rates of cognitive decline. The cardiovascular
      health study.
AB  - AIM: To estimate an equivalent to the Modified Mini-Mental State Exam (3MSE), and
      to compare changes in the 3MSE with and without the estimated scores. METHODS:
      Comparability study on a subset of 405 participants, aged >or=70 years, from the
      Cardiovascular Health Study (CHS), a longitudinal study in 4 United States
      communities. The 3MSE, the Telephone Interview for Cognitive Status (TICS) and
      the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were
      administered within 30 days of one another. Regression models were developed to
      predict the 3MSE score from the TICS and/or IQCODE, and the predicted values were
      used to estimate missing 3MSE scores in longitudinal follow-up of 4,274 CHS
      participants. RESULTS: The TICS explained 67% of the variability in 3MSE scores,
      with a correlation of 0.82 between predicted and observed scores. The IQCODE
      alone was not a good estimate of 3MSE score, but improved the model fit when
      added to the TICS model. Using estimated 3MSE scores classified more participants
      with low cognition, and rates of decline were greater than when only the observed
      3MSE scores were considered. CONCLUSIONS: 3MSE scores can be reliably estimated
      from the TICS, with or without the IQCODE. Incorporating these estimates captured
      more cognitive decline in older adults.

PMID- 19407462
TI  - Silent small-vessel cerebrovascular disease and silent myocardial ischemia in
      families with premature coronary disease.

PMID- 19407463
TI  - Assessment of right ventricular function using tissue Doppler imaging in infants
      with pulmonary hypertension.
AB  - BACKGROUND: In infants with pulmonary hypertension (PHT), right ventricular (RV)
      function may be altered and contribute to disease severity. Tissue Doppler
      imaging (TDI) is a new echocardiographic modality which directly measures
      myocardial velocities and may allow quantitative assessment of systolic and
      diastolic ventricular function in infants. OBJECTIVE: To measure and compare RV
      myocardial velocities in infants with PHT and in normal control infants, using
      TDI. METHODS: This was a prospective case-control study. Twenty-eight control
      infants and 15 infants with PHT, of whom 11 had congenital diaphragmatic hernia
      (CDH), were recruited. TDI was used to obtain systolic and diastolic myocardial
      velocities in the RV and interventricular septum in all infants. RESULTS: There
      were significant reductions in systolic isovolumic contraction velocity (IVV; 5.3
      vs. 6.6 cm/s) and systolic ejection velocity (S; 6.6 vs. 9.2 cm/s) in the PHT
      group compared to the control group. Early diastolic myocardial velocity, E', was
      also significantly reduced in the RV in the PHT infants compared to controls (
      4.3 vs. 8.6 cm/s). The same significant reductions in systolic and early
      diastolic TDI velocities were observed in the subgroup of CDH infants alone.
      CONCLUSIONS: TDI permits non-invasive assessment of RV myocardial velocities in
      infants. Reduced systolic and diastolic velocities in PHT may represent impaired
      systolic contraction and early diastolic relaxation. Therapies which target
      inotropic and lusitropic function may be appropriate in infants with PHT and RV
      dysfunction. The load-dependency of TDI measures in infants and the effects of
      specific therapies on RV function in PHT require further investigation.

PMID- 19407464
TI  - The right ventricle and persistent pulmonary hypertension of the newborn.
      Commentary on Patel N et al.: assessment of right ventricular function using
      tissue Doppler imaging in infants with pulmonary hypertension (Neonatology
      2009;96:193-199).

PMID- 19407465
TI  - Necrotizing enterocolitis--150 years of fruitless search for the cause.
AB  - Necrotizing enterocolitis (NEC) is not a new disease but one that has been
      reported since special care units began to house preterm infants. It was observed
      in foundling hospitals in Paris [Billard, 1828] and Vienna [Bednar, 1850] and, as
      it occurred in clusters, was regarded as a nosocomial infection in the infant
      hospitals of Zurich [Willi, 1944] and Berlin [Ylppo, 1931]. Clinical and patho
      anatomic characterization was achieved by Schmidt and Quaiser in 1952. The
      unproven hypothesis of mesenteric hypoperfusion as a major etiological factor
      arose from animal models and analogous perforating disorders in term infants.
      Despite similarities between NEC and clostridial infections, few studies employed
      anaerobic culture techniques. The pathogenesis remains unclear and its
      distinction from related disorders uncertain. It is unlikely that strategies to
      prevent NEC will be successful unless the disease is better understood.

PMID- 19407466
TI  - Liver enzymes cannot be used to predict liver damage after global hypoxia
      ischemia in a neonatal pig model.
AB  - BACKGROUND: The term newborn pig is an established model for studying both brain
      and organ pathology after hypoxia-ischemia (HI). Serial liver enzyme activity is
      often used to predict liver injury but little is known about the relation between
      consecutive values of different liver enzymes and histologically verified liver
      injury. OBJECTIVE: To determine whether plasma values of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase
      (LDH) differed between newborn pigs with liver injures and pigs with normal
      livers after a severe global HI insult. METHODS: Nineteen < or =36-hour-old pigs
      underwent a 45-min global HI insult followed by 72-hour survival. Four
      histological sections from standardized areas within each liver were examined.
      Areas under the curve (AUC) for the enzymes were calculated and compared between
      pigs with pathological changes in the liver (n = 12) and pigs with normal liver
      histology (n = 7). RESULTS: No differences in AUC for the enzyme values were seen
      between the groups. However, in pigs with liver injuries a transient significant
      increase in LDH at the end of the HI insult (928 U/l (567-1,031)) was seen
      compared to the baseline value (679 U/l (548-866), p = 0.010). Significantly more
      liver injury was seen in animals with the umbilical vein catheter (UVC) tip
      inserted into the liver (p = 0.040) compared to animals with the UVC tip located
      outside the liver. CONCLUSIONS: In newborn pigs subjected to global HI, only LDH
      increases alongside pathological changes in the liver. Normal values of ALT and
      AST do not exclude hepatic injury.

PMID- 19407467
TI  - Periventricular echodensity measured with the integrated backscatter system: from
      a qualitative assessment to a quantitative approach.
AB  - BACKGROUND: The degree of periventricular white matter echodensity in preterm
      infants has been utilized as a sign of the early ultrasonographic appearance of
      periventricular leukomalacia, and this has been called periventricular
      echodensity (PVE). OBJECTIVES: The aim of this study was to quantitatively
      measure PVE utilizing a new method which is called calibrated integrated
      backscatter (calibrated IB). METHODS: Eighty-eight preterm infants (extremely low
      birth weight infants, n = 17; very low birth weight infants, n = 26; low birth
      weight infants, n = 45) without any CNS abnormality were enrolled. IB is the
      returned sound pressure against supersonic waves sent from an ultrasonographic
      machine. The IB of the choroid plexus and periventricular white matter in the
      subrolandic area were measured on a parasagittal cerebral image. The degree of
      PVE was defined by subtracting the IB of the choroid plexus from that of the
      periventricular white matter in the subrolandic area (calibrated IB of PVE).
      RESULTS: The intraobserver and interobserver correlations were both excellent
      (between 0.87 and 0.98 as correlation coefficients). There was a trend for the
      calibrated IB of PVE to decrease in accordance with time after birth, with a
      significant difference in very low birth weight and low birth weight infants.
      CONCLUSIONS: The objectively measured brightness of PVE was comparable to that of
      the choroid plexus irrespective of the size of the infants. Measurement of the
      calibrated IB of PVE might be a reliable method to assess PVE.

PMID- 19407468
TI  - Skin care in the NICU patient: effects of wipes versus cloth and water on stratum
      corneum integrity.
AB  - BACKGROUND: NICU patients are at risk of skin breakdown due to prematurity,
      irritant exposure, medical status and stress. There is a need to minimize damage,
      facilitate skin development and reduce infection risk, but the literature on the
      effects of skin care practices in NICU patients is limited. OBJECTIVES: To test
      the hypothesis that baby diaper wipes with emollient cleansers and a soft cloth
      would minimize skin compromise relative to cloth and water. METHODS: In 130 NICU
      infants (gestational age 23-41 weeks, at enrollment 30-51 weeks), measurements of
      skin condition, i.e., skin erythema, skin rash, transepidermal water loss (TEWL)
      and surface acidity (pH), within the diaper and at diaper and chest control sites
      were determined daily for 5-14 days using standardized methods. Treatments were
      randomly assigned based on gestational age and starting skin irritation score:
      wipe A, wipe B, and the current cloth and water NICU standard of care. RESULTS:
      Perineal erythema and TEWL were significantly lower for wipes A and B than cloth
      and water beginning at day 5 for erythema (scores of 1.11 +/- 0.05, 1.2 +/- 0.05,
      and 1.4 +/- 0.06, respectively) and day 7 for TEWL (28.2 +/- 1.6, 28.8 +/- 1.6,
      and 35.2 +/- 1.6 g/m(2)/h, respectively). Wipe B produced a significantly lower
      skin pH (day 5, 5.47 +/- 0.03) than wipe A (5.71 +/- 0.03) and cloth and water
      (5.67 +/- 0.04). The starting skin condition, stool total, age and time on
      current standard impacted the outcomes. CONCLUSIONS: Both wipes are appropriate
      for use on medically stable NICU patients, including both full and preterm
      infants, and provide more normalized skin condition and barrier function versus
      the cloth and water standard. Wipe B may facilitate acid mantle development and
      assist in colonization, infection control and barrier repair. Neonatal skin
      continues to change for up to 8 weeks postnatally, presumably as it adapts to the
      dry extra-uterine environment.

PMID- 19407469
TI  - The effect of angiotensin II on the number of macula densa cells through the AT1
      receptor.
AB  - The present study was performed to obtain information about a possible
      correlation between the activity of the renin-angiotensin system and the
      stereological features of the macula densa (MD). In normal kidneys, the numbers
      of angiotensin II AT1 receptors were estimated in MD cells and in the neighboring
      tubular cells. The total volumes of MD, MD cells, neighboring tubular cells, and
      the total number of MD cells, were measured in normal and candesartan-treated
      rats (15 mg/kg/day over 21 days). In the normal kidneys, the relative number of
      AT1 receptors in MD cells [mean = 0.17 (CV = 0.23)] was significantly (p = 0.03)
      lower than that in normal tubular cells [0.25 (0.21)]. A significant difference
      (p < 0.01) was observed in the total volume between MD cells [515 microm(3)
      (0.14)] and normal tubular cells [984 microm(3) (0.19)]. Candesartan treatment
      significantly elevated (p < 0.01) the total volume of the MD, whereas the total
      number of MD cells was increased [from 14.2 (0.11) to 19.5 (0.11)]. The results
      demonstrated that the transdifferentiation from normal tubular cells to MD cells
      can be controlled by pharmacological means. The structural features of MD
      controlled by the renin-angiotensin system may be one of the important factors
      governing the sensitivity of tubuloglomerular feedback.

PMID- 19407470
TI  - Circulating and disseminated tumor cells in the clinical management of breast
      cancer patients: unanswered questions.
AB  - Breast cancer is the most common cancer in women. Although survival rates have
      improved with the use of new therapeutic agents, many issues remain unresolved
      and new predictive and prognostic factors are needed in clinical practice.
      Several studies have suggested a prognostic and predictive role for circulating
      and disseminated tumor cells in metastatic disease and adjuvant treatment.
      Because of recent technological advances, oncologists have gained a new
      perspective on this disease. Circulating tumor cells could be both a new tumor
      marker as well as a tool to gain novel insight into the natural history of this
      neoplastic disease.

PMID- 19407471
TI  - Downregulation of carcinoembryonic antigen-related cell adhesion molecule 1 in
      oral squamous cell carcinoma: correlation with tumor progression and poor
      prognosis.
AB  - OBJECTIVE: To identify genes associated with therapeutic targets of oral squamous
      cell carcinoma (OSCC), we compared gene expression profiles in OSCC-derived cell
      lines with human normal oral keratinocytes. METHODS: We analyzed the gene
      expression profiles of OSCCs using Affymetrix GeneChip analysis. The identified
      genes were analyzed by an Ingenuity Pathway Analysis tool to identify networks of
      interacting genes. A candidate gene was further evaluated for the expression
      status of the mRNA and protein in OSCC-derived cell lines and primary OSCCs.
      RESULTS: The microarray data identified 188 genes downregulated in OSCC-derived
      cell lines, and the genetic pathways associated with expression changes were
      generated. Among the genes mapped to the network with the highest significance,
      carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was analyzed
      further. CEACAM1 mRNA and protein were frequently downregulated in OSCC-derived
      cell lines compared with human normal oral keratinocytes. Immunohistochemical
      analysis showed that primary OSCCs were significantly decreased in CEACAM1.
      Moreover, CEACAM1 expression was correlated with the TNM staging. We also found
      that CEACAM1-negative expression was significant both for disease-free (p =
      0.036) and overall survival (p = 0.032). CONCLUSION: Repression of CEACAM1 could
      contribute to cancer progression and may indicate a poor prognosis for patients
      with OSCC.

PMID- 19407472
TI  - Direct integration of government funding and family support for musculoskeletal
      tumor care in a resource-constrained country.
AB  - BACKGROUND: Malignant musculoskeletal tumor (MMST) outcome reflects the level of
      supportive care provided. In Nigeria, the supportive care available to patients
      with MMST is limited by a lack of funding. Patients often present late, and
      receive only orthodox care as psychosocial care is not available. We evaluated
      the effect of direct incorporation of government funding and family support on
      MMST patient acceptance and completion of treatment. METHODS: A 3-year
      prospective multicenter intention-to-treat study was undertaken in a tertiary
      care setting. The first step was a nonselective randomization of MMST patients
      into 2 groups, Wesley Guilds Hospital Firm A (WGHFA) and Wesley Guilds Hospital
      Firm B (WGHFB) using the computer software Excel. The control group was WGHFA,
      which consisted of patients who self-financed their oncology care. The WGHFB
      patients' governments (local or state) provided funds according to medical
      reports and the patients had relatives who offered psychosocial support. The
      second step entailed treatment (surgery, chemotherapy and radiotherapy) and
      follow-up. Outcome measures were the interval between presentation at hospital
      and surgical intervention, acceptability of limb amputation, completeness of
      treatment courses, duration of hospital stay and mortality. The reproducibility
      of the methodology was reappraised at the Federal Medical Center. Kruskal-Wallis
      analysis was used, and an alpha error of <0.05 at a CI of 95% was taken to be
      significant. RESULTS: A total of 112 cases of MMST were managed during the study
      period. Seventy-one (63.4%; 37 WGHFA; 34 WGHFB) met the inclusion criteria. Age,
      sex, tribe, religion, comorbid factors and mean weekly income were not
      significant factors influencing improved MMST care among the WGHFB patients. 32
      WGHFB versus 7 WGHFA patients accepted the treatment plan. The mean duration of
      hospital stay before surgery (p < 0.001), discharge against medical advice (p <
      0.000), limb salvage (21 vs. 2, p < 0.001), limb amputation (3 vs. 12, p < 0.05,
      95% CI 8.3-37.9), completeness of treatment (33 vs. 7, p < 0.05), mean duration
      of hospital stay, in days (23 vs. 39, p < 0.05) and mortality at 1-year follow-up
      (13 vs. 28, p < 0.02) were significant. CONCLUSION: The cost of cancer care is a
      challenge for patients with MMST in a resource-constrained country such as
      Nigeria. Direct integration of the government and family into MMST care will
      serve as a link between the cancer patient and the source of funds. It raises the
      possibility of an effective psychosocial approach to improve patient outcome
      through enhanced treatment acceptability and completion, and so reduce morbidity
      and short-term mortality.

PMID- 19407473
TI  - Hyperfractionated accelerated radiotherapy versus conventional fractionation both
      combined with chemotherapy in patients with locally advanced head and neck
      carcinomas: a retrospective analysis of a monoinstitutional series.
AB  - OBJECTIVE: Hyperfractionated accelerated radiotherapy (HART) has been combined
      with chemotherapy (CC) for locally advanced head and neck cancer, but no data
      from randomized trials are available for a comparison with conventionally
      fractionated radiotherapy (CFRT) and CC. METHODS: This monoinstitutional
      retrospective study compares the results of both treatment schedules: 315
      patients with locally advanced carcinoma (UICC stage III and IV) of the oral
      cavity and the orohypopharynx were treated from January 1990 to March 2006 with a
      radiochemotherapy combination based on mitomycin C and fluorouracil (HART-CC: 203
      patients, CFRT-CC: 112 patients, total dose: 70-72 Gy) with curative intent.
      RESULTS: Two- and 4-year survival was 60 and 42 (HART-CC) and 59 and 42% (CFRT
      CC; p = 0.82, log-rank test), respectively. Using multivariate Cox regression,
      pretreatment hemoglobin level, N stage, tumor site but not the year of treatment,
      gender and T stage were significant prognosticators for survival. For
      locoregional control, only N stage was significant. The prognostic value of these
      pretreatment factors did not variate with the fractionation schedule used.
      CONCLUSIONS: In combination with CC, there was no trend towards an improved
      efficacy of HART in comparison with CFRT.

PMID- 19407475
TI  - Suppression of retinal neovascularization by small-interference RNA targeting
      erythropoietin.
AB  - OBJECTIVE: To observe the effect of inhibition of retinal neovascularization by
      small-interference RNA (siRNA) targeting erythropoietin (EPO). METHOD: Three
      siRNAs against EPO were designed and synthesized. Then they were transfected to
      NIH/3T3 cells by liposomes. RT-PCR and Western blot were used to evaluate the
      efficacy of siRNA in attenuating EPO expression in NIH/3T3 cells. One-week-old
      C57BL/6J mice were exposed to 75 +/- 2% oxygen for 5 days, then they were
      returned to room air to induce retinal neovascularization. The siRNA type shown
      as most powerful in reducing EPO expression in vitro was intravitreally injected
      in the treatment group. Retinal neovascularization was evaluated by angiography
      with injection of fluorescein-dextran and quantification of neovascular
      proliferative retinopathy after 5 days in room air. Moreover, RT-PCR and
      immunoblot analysis were used to determine whether local administration of siRNA
      could affect the expression of EPO in murine retinas. RESULTS: Among the 3
      designed siRNAs (named siEPO1-3), siEPO2 is the most efficient in inhibiting EPO
      expression. In this murine model of oxygen-induced retinopathy, retinal
      neovascularization in the eyes with siEPO2 injection was significantly reduced
      compared with that of the contralateral control eyes. Similarly, histological
      analysis indicates that the number of neovascular nuclei protruding into the
      vitreous cavity was decreased compared to the control eyes. Furthermore, the
      expression of EPO in the retinas injected with siEPO2 was dramatically decreased.
      CONCLUSION: siRNA against EPO could inhibit experimental retinal
      neovascularization by reducing EPO expression in the retinas of mice. It may
      provide a powerful and novel therapeutic tool for ischemia-induced retinal
      diseases.

PMID- 19407474
TI  - Neoadjuvant 5 fluorouracil-cisplatin chemoradiation effect on survival in
      patients with resectable pancreatic head adenocarcinoma: a ten-year single
      institution experience.
AB  - OBJECTIVES: It is the aim of this study to assess the outcome of patients who
      received neoadjuvant 5-fluorouracil-cisplatin chemoradiation (CRT) for stage
      I/III pancreatic adenocarcinoma. METHODS: Eligible patients (n = 101) received
      radiation therapy (45 Gy) associated with continuous infusion of 5-fluorouracil
      accompanied by a cisplatin bolus. RESULTS: Of the 102 patients enrolled in the
      study, 26 patients had progression of cancer during treatment and were deemed
      unresectable; 1 patient died during CRT of septic shock. Sixty-two of 75
      remaining patients underwent pancreaticoduodenectomy. The overall median survival
      of all 102 patients in the study was 17 months, with a 5-year survival of 10%.
      For patients who underwent resection, the median survival was 23 months.
      Correspondingly, the median survival was 11 months for the 40 unresected patients
      (p = 0.002). The 5-year survivals for resected and unresected patients were 18
      and 0% (p = 0.01), respectively. A complete pathological response to neoadjuvant
      CRT was noted for 8 patients (13%). Margin and lymph node positivity was present
      in 5 (8%) and 15 (24%) patients, respectively. There was documented local
      recurrence in 8 (13%) and distant recurrence in 36 (58%) patients, with the liver
      being the most common site. CONCLUSION: Neoadjuvant 5-fluorouracil-based CRT had
      a limited impact on survival but appeared to be associated with improved local
      control.

PMID- 19407476
TI  - Interferon-gamma treatment accelerates and aggravates autoimmune pancreatitis in
      the MRL/Mp-mouse.
AB  - BACKGROUND: T helper 1 cell-released pro-inflammatory cytokines have been
      implicated in the pathogenesis of autoimmune pancreatitis (AIP), but the
      experimental database is small. Here, we have directly tested the effects of
      interferon-gamma (IFN-gamma) by applying it to AIP-prone MRL/Mp mice. METHODS:
      MRL/Mp-mice were treated for 4 weeks with IFN-gamma. Severity of AIP was assessed
      by histopathology, laboratory findings and gene expression analysis. RESULTS:
      Using a histopathological score from 0 (healthy pancreas) to 4 (severe AIP), we
      found that IFN-gamma treatment strongly increased severity of pancreatic lesions.
      IFN-gamma also caused pancreatic accumulation of CD4-, CD8-, C11b- and CD138
      positive cells, and enhanced pancreatic mRNA expression of interleukin (IL)-1
      beta, transforming growth factor-beta and IFN-gamma itself. In the serum of IFN
      gamma-treated mice, higher lipase activities but normal glucose levels were
      observed. DISCUSSION: IFN-gamma accelerates and aggravates AIP in MRL/Mp mice.
      IFN-gamma-enhanced AIP of MRL/Mp mice may serve to study pathophysiology, and to
      test diagnostic/therapeutic approaches.

PMID- 19407477
TI  - A study of pancreatic function among subjects over ninety years of age.
AB  - BACKGROUND: Among the various studies of pancreatic function in the elderly
      published so far, none have dealt with subjects over 90 years of age. The aim of
      this study was to examine pancreatic function in healthy individuals over 90
      years old. METHODS: Sixty-eight healthy noninstitutionalized elderly persons,
      aged 91-104 years, with a mean age of 95 years, and 63 younger controls were
      studied. Pancreatic function was studied by determining fecal elastase 1
      concentration. In addition to this test, we also measured serum amylase,
      pancreatic isoamylase and lipase in 53 of the 68 elderly subjects. RESULTS: All
      but 1 of the 68 elderly subjects had normal elastase 1 values; the one who did
      not had a value slightly below normal. No significant difference with controls
      was found. Serum pancreatic enzymes were normal in almost all of the 53 elderly
      studied; 3 had a mild elevation only of amylase and 1 had a persistent elevation
      of amylase, pancreatic isoamylase and lipase. CONCLUSIONS: In subjects over 90
      years of age, exocrine pancreatic function continues to be normal; if an
      impairment occurs, it is mild and not significant for digestion of food. In
      addition, serum pancreatic enzymes remain within normal limits in the vast
      majority of cases.

PMID- 19407478
TI  - Pancreatic damage after the first episode of acute alcoholic pancreatitis and its
      association with the later recurrence rate.
AB  - BACKGROUND: Acute alcoholic pancreatitis (AAP) recurs in up to half of the
      patients, continuous alcohol consumption being an important risk factor. Changes
      in pancreatic function and morphology after acute pancreatitis have been
      characterized previously, but their association with later recurrences has not
      been adequately studied. PATIENTS AND METHODS: In this prospective follow-up
      study, the pancreatic function of 54 patients (47 males and 7 females) with a
      median age of 49 years (range 25-71) and morphology (35 patients) were evaluated.
      Pancreatic morphology was evaluated by secretin-stimulated magnetic resonance
      pancreatography (SMRP). Patients were evaluated early (baseline) and at 2 years
      after the first episode of AAP. In order to evaluate later recurrences, the
      patients were followed for a median of 47 (range 28-66) months. RESULTS: Of the
      46 patients without previous diabetes, 17 patients (37%) developed impaired
      glucose metabolism during the 2 years following the first AAP. The prevalence of
      exocrine dysfunction decreased from 39% at baseline to 9% at 2 years. Of the
      patients with severe pancreatitis (n = 13, 24%), 31% had elevated glycosylated
      haemoglobin levels compared to 7% in patients with mild pancreatitis [p = 0.05,
      odds ratio (OR): 5.5, 95% confidence interval (CI): 1.04-29.0]. Twenty percent
      (7/35) of the patients had changes consistent with chronic pancreatitis on
      baseline SMRP, which persisted in all cases. Of the 29% patients with acute
      changes on baseline SMRP, the acute changes resolved in 50% and chronic
      pancreatitis was detected in the remaining 50% at 2 years. Development of chronic
      changes did not depend on continued alcohol consumption, as it was also found in
      3 patients practising complete abstinence following their first attack of AAP.
      The presence of a chronic pseudocyst at 2 years predicted pancreatitis when
      compared to patients lacking pseudocyst formation: 4 (80%) versus 5 (17%) (p =
      0.01, OR: 20.0, 95% CI: 1.83-219). CONCLUSION: The severity of the first episode
      of AAP was associated with deteriorated diabetes control, but not with pancreatic
      exocrine dysfunction at 2 years. The number of patients with chronic changes on
      SMRP increased independently of alcohol consumption. Chronic pseudocyst formation
      seen on SMRP 2 years after AAP was significantly associated with recurrence of
      pancreatitis.

PMID- 19407479
TI  - Dyslipidaemic pancreatitis clinical assessment and analysis of disease severity
      and outcomes.
AB  - INTRODUCTION: The relationship between pancreatitis and dyslipidaemia is unclear.
      PATIENTS AND METHODS: Admissions with acute pancreatitis were prospectively
      evaluated. A comparison of the demographic profile, aetiology, disease severity
      scores, complications and deaths was made in relationship to the lipid profiles.
      RESULTS: From June 2001 to May 2005, there were 230 admissions. The pancreatitis
      was associated with alcohol (63%), gallstones (18%), idiopathic (9%) and isolated
      dyslipidaemia (10%). Dyslipidaemia was significantly different between the two
      predominant race groups: Indian 50.5% and African 17.9% (p < 0.000017). Seventy
      eight (34%) had associated dyslipidaemia and 152 (66%) were normolipaemic at
      admission. The average body mass index was higher in the dyslipidaemic group (27
      +/- 6) than in the normolipaemic group (24.5 +/- 6.20; p = 0.004). The mortality
      rate was similar between the dyslipidaemic and normolipaemic patients (10 and 8%,
      respectively) and unrelated to race (p = 0.58). The 9 deaths in the dyslipidaemic
      group occurred in those with persistent hypertriglyceridaemia irrespective of its
      level (p = 0.003). CONCLUSION: Dyslipidaemic pancreatitis was more common in the
      Indian ethnic group. Adverse outcomes in those with dyslipidaemia were
      predominantly associated with hypertriglyceridaemia.

PMID- 19407480
TI  - Alcohol pretreatment increases hepatic and pulmonary injury in experimental
      pancreatitis.
AB  - BACKGROUND: Systemic complications including pancreatitis-associated lung injury
      (PALI) are critical factors that determine the outcome of severe necrotizing
      pancreatitis (SNP). The aim of the present study was to evaluate the role of
      chronic alcohol exposure on the development of PALI. METHODS: 48 rats were fed
      either a Lieber deCarli control or alcohol diet for 6 weeks. After completion,
      SNP was induced by intraductal infusion of bile salt followed by intravenous
      infusion of cerulein over 6 h. Control animals received i.v. Ringer's solution.
      Intravital microscopy of the liver was performed 6 h after induction of SNP to
      evaluate hepatic perfusion and leukocyte adhesion. Serum parameters, edema,
      inflammation, and histological changes were evaluated at 12 h. IL-6 levels were
      evaluated in portal venous and systemic blood as well as in pancreatic tissue
      homogenates. RESULTS: Alcohol pretreatment did not affect pancreatic injury in
      SNP. PALI was aggravated after alcohol ingestion. These animals showed increased
      hepatic microcirculatory disturbances, compared to SNP alone. IL-6 showed peak
      levels in SNP with alcohol pretreatment, although they were also elevated in SNP
      alone. Systemic levels of IL-6 were higher than in the portal vein. CONCLUSION:
      In SNP, alcoholic pretreatment increases pulmonary damage, while pancreatic
      injury is identical. The liver seems to participate in this effect by increased
      hepatic cytokine release.

PMID- 19407481
TI  - Identification of genomic alterations associated with the aggressiveness of
      pancreatic cancer using an ultra-high-resolution CGH array.
AB  - BACKGROUND: Genomic alterations present in pancreatic adenocarcinoma have been
      described only partially. In addition, the relations between these alterations
      and the aggressiveness of the phenotype remain unknown. METHODS: Genomic DNA and
      total RNA from 5 pancreatic cell lines, of which 2 have an aggressive phenotype
      and are gemcitabine-resistant (Mia-Paca2 and Panc-1), and 3 less aggressive and
      gemcitabine-sensitive (Capan-1, Capan-2 and BxPC3), have been purified. DNA
      abnormalities have been analyzed using an ultra-high-resolution CGH array and
      mRNA expression was studied with an Affymetrix GeneChip expression array.
      RESULTS: We identified 573 amplified and 30 deleted genes common to all 5 cell
      lines. Some of them have already been described, whereas other genes, implicated
      in signal transduction, apoptosis, cell cycle or cell migration, are described
      for the first time as being related to this cancer. Comparison of genomic
      abnormalities between the 2 most aggressive and the 3 less aggressive cell lines
      led to the identification of 368 genes specifically amplified in the aggressive
      cell lines. However, no specific gene deletion seems to be associated with the
      aggressive phenotype. CONCLUSION: Using a high-resolution approach, we could
      precisely describe the genomic alterations associated with pancreatic
      adenocarcinoma and determine those associated with an aggressive phenotype.

PMID- 19407482
TI  - Identification of a novel kindred with familial pancreatitis and pancreatic
      cancer.
AB  - BACKGROUND/AIMS: Hereditary pancreatic cancer comprises about 10% of pancreatic
      cancer cases. Multiple causative mutations have been identified. Here we describe
      a pancreatitis/pancreatic cancer (P/PC) family, which demonstrates pancreatitis
      and pancreatic cancer resulting from an uncharacterized mutation. METHODS: Family
      members completed evaluations to determine signs of mutation status. Select
      patients were screened for mutations associated with hereditary pancreatic
      diseases. RESULTS: In generation II, 12 siblings exhibit 6 cases of pancreatitis,
      3 pancreatic cancer, and 2 obligate carrier status. The average age at
      pancreatitis diagnosis of enrolled members is 32.5 years; average age at
      pancreatic cancer diagnosis is 59 years. There is no association with known
      cancer syndromes. Those affected generally present with mild epigastric pain, and
      CT scans demonstrate characteristic fatty infiltration of the pancreatic body and
      tail with sparing of the head and neck. Full sequence analysis of genes
      associated with hereditary pancreatic disease failed to demonstrate known
      mutations or polymorphisms. CONCLUSION: Based upon pedigree evaluation and
      preliminary DNA analysis, we believe that the family members with P/PC carry a
      novel genetic mutation resulting in hereditary pancreatitis. This mutation is
      autosomal dominant, expressed with high penetrance, and is part of a unique
      hereditary syndrome that significantly increases pancreatic cancer risk.

PMID- 19407483
TI  - Infected necrosis in severe pancreatitis--combined nonsurgical multi-drainage
      with directed transabdominal high-volume lavage in critically ill patients.
AB  - BACKGROUND: Infection of pancreatic necrosis is a life-threatening complication
      during the course of acute pancreatitis. In critically ill patients, surgical or
      extended endoscopic interventions are associated with high morbidity and
      mortality. Minimally invasive procedures on the other hand are often insufficient
      in patients suffering from large necrotic areas containing solid or purulent
      material. We present a strategy combining percutaneous and transgastric drainage
      with continuous high-volume lavage for treatment of extended necroses and liquid
      collections in a series of patients with severe acute pancreatitis. PATIENTS AND
      METHODS: Seven consecutive patients with severe acute pancreatitis and large
      confluent infected pancreatic necrosis were enrolled. In all cases, the first
      therapeutic procedure was placement of a CT-guided drainage catheter into the
      fluid collection surrounding peripancreatic necrosis. Thereafter, a second
      endosonographically guided drainage was inserted via the gastric or the duodenal
      wall. After communication between the separate drains had been proven, an
      external to internal directed high-volume lavage with a daily volume of 500 ml up
      to 2,000 ml was started. RESULTS: In all patients, pancreatic necrosis/liquid
      collections could be resolved completely by the presented regime. No patient died
      in the course of our study. After initiation of the directed high-volume lavage,
      there was a significant clinical improvement in all patients. Double drainage was
      performed for a median of 101 days, high-volume lavage for a median of 41 days.
      Several endoscopic interventions for stent replacement were required (median 8).
      Complications such as bleeding or perforation could be managed endoscopically,
      and no subsequent surgical therapy was necessary. All patients could be dismissed
      from the hospital after a median duration of 78 days. CONCLUSION: This approach
      of combined percutaneous/endoscopic drainage with high-volume lavage shows
      promising results in critically ill patients with extended infected pancreatic
      necrosis and high risk of surgical intervention. Neither surgical nor endoscopic
      necrosectomy was necessary in any of our patients.

PMID- 19407484
TI  - Association of novel chymotrypsin C gene variations and haplotypes in patients
      with chronic pancreatitis in Chinese in Taiwan.
AB  - BACKGROUND/AIMS: Variations and haplotypes of the chymotrypsin C (CTRC) gene in
      Chinese patients with chronic pancreatitis (CP) and control subjects with
      genotype-phenotype correlation were investigated. METHODS: One hundred and twenty
      six patients with CP were analyzed. The entire sequence of coding regions of
      exons 2, 3 and 7 and their neighboring intronic regions in introns 1, 2 and 6 of
      the CTRC gene were analyzed using PCR sequence-specific primers and direct
      sequencing. The exonic region of exon 7 and the neighboring intronic region of
      intron 6 were also analyzed in 90 geographically matched healthy control
      subjects. RESULTS: In total, 4 novel variations were identified in exons 2, 3 and
      7 in 3 CP patients. A total of 2.3% (3/126) of our CP patients carried variations
      of the CTRC gene. We also first identified six new intronic variations in intron
      6 which had not been reported before. The GAGGGG, GAGGAG and GAGTAG haplotypes
      assembled by six locus intronic variations c.640-41/c.640-40/c.640-39/c.640
      37/c.640-36/c.640-35 in intron 6 were associated with a significantly higher
      susceptibility risk of CP (OR 66.75, 37.00, and 9.37, respectively). CONCLUSION:
      Novel CTRC gene variations and haplotypes are associated with CP in a Chinese
      population.

PMID- 19407486
TI  - Anti-hepatitis B virus activity and mechanisms of recombinant human serum albumin
      interferon-alpha-2b fusion protein in vitro and in vivo.
AB  - AIMS: To evaluate the anti-hepatitis B virus (anti-HBV) effects and mechanisms of
      recombinant human serum albumin-interferon-alpha-2b fusion protein (rHSA-IFNalpha
      2b) in vitro and in vivo. METHODS: The inhibiting effects on HBV replication were
      examined in the HepG2 2.2.15 cell line and in ducks, and the expressions of
      signal transducers and transactivator 1 (STAT1), IFN-stimulated gene factor 3
      (ISGF3) and 2',5'-oligoadenylate synthetase 1 (OAS1) were investigated by the
      reverse transcription-polymerase chain reaction (RT-PCR) and Western blot
      analysis. RESULTS: In vitro,at concentrations from 0.075 to 1.2 nmol/l, rHSA
      IFNalpha-2b inhibited the releases of extracellular hepatitis B surface antigen,
      hepatitis B e antigen and HBV DNA in a dose-dependent manner; rHSA- IFNalpha-2b
      also increased the levels of STAT1, ISGF3 and OAS1. In vivo, rHSA-IFNalpha-2b
      reduced the levels of alanine aminotransferase, aspartate aminotransferase, total
      bilirubin and duck hepatitis B virus (DHBV) DNA in the sera of DHBV-infected
      ducks. CONCLUSIONS: We provide the first evidence that rHSA-IFNalpha-2b
      significantly inhibits HBV replication in HepG2 2.2.15 cells and in ducks, and
      that the antiviral effect of rHSA-IFNalpha-2b in vivo is more potent than that of
      IFNalpha-2b. The anti-HBV mechanism probably operates by triggering the JAK-STAT
      signaling pathway and increasing the expression of OAS1.

PMID- 19407487
TI  - Inhibition of cervical cancer cell growth through activation of upstream kinases
      of AMP-activated protein kinase.
AB  - AMP-activated protein kinase (AMPK) is a critical energy-balancing sensor in the
      regulation of cellular metabolism in response to external stimuli. Emerging
      evidence has suggested that AMPK is a potential therapeutic target for human
      cancers. AICAR, one of the pharmacological AMPK activators, has been widely used
      to suppress cancer cell growth through activation of LKB1, an upstream kinase of
      AMPK. However, frequent mutations and deletions of LKB1 found in some cancer
      cells limit the application of AICAR as an efficient therapeutic drug. Here we
      show that an alternative pharmacological AMPK activator, A23187, was able to
      inhibit cervical cancer cell growth through activation of Ca(2+)/calmodulin
      dependent protein kinase kinase beta, another upstream kinase of AMPK. Using
      cervical cancer cell models, we found that HeLa (LKB1-deficient cell) responded
      less to the anti-proliferative effect exerted by AICAR treatment (p < 0.001)
      compared with CaSki and C41 (LKB1-expressing cells). Conversely, the anti
      proliferative effect was increased significantly in HeLa but not in CaSki and C41
      cells under treatment by A23187 (p < 0.001). Moreover, co-treatment of AICAR and
      A23187 was able to further enhance the inhibitory effect on cell growth of Hela,
      CaSki and C41 cells. Notably, both AICAR and A23187 exerted the anti
      proliferative effect on cervical cancer cells by suppressing AMPK/mTOR signalling
      activity. These data suggest that A23187 could be an alternative potential
      therapeutic drug used for anti-proliferation in LKB1-deficient cancer cells.

PMID- 19407485
TI  - Epigenetic silencing of MicroRNA miR-107 regulates cyclin-dependent kinase 6
      expression in pancreatic cancer.
AB  - Aberrant expression of microRNAs (miRNAs) has emerged as an important hallmark of
      cancer. However, the putative mechanisms regulating miRNAs per se are only
      partially known. It is well established that many tumor suppressor genes in human
      cancers are silenced by chromatin alterations, including promoter methylation and
      histone deacetylation. We postulated that miRNAs undergo similar epigenetic
      inactivation in pancreatic cancer. Two human pancreatic cancer cell lines -
      MiaPACA-2 and PANC-1 - were treated with the demethylating agent, 5-aza-2'
      deoxycytidine (5-Aza-dC) or the histone deacetylase inhibitor, trichostatin A, as
      well as the combination of the two. Expression of miRNAs in control and treated
      cell lines was assessed using a custom microarray platform. Fourteen miRNAs were
      upregulated two-fold or greater in each of the cell lines following exposure to
      both chromatin-modifying agents, including 5 that were in common (miR-107, miR
      103, miR-29a, miR-29b, and miR-320) to both MiaPACA-2 and PANC-1. The
      differential overexpression of miR-107 in the treated cancer cell lines was
      confirmed by Northern blot assays. Methylation-specific PCR assays for assessment
      of CpG island methylation status in the 5' promoter region of the miR-107 primary
      transcript demonstrated complete loss of methylation upon exposure to 5-Aza-dC.
      Enforced expression of miR-107 in MiaPACA-2 and PANC-1 cells downregulated in
      vitro growth, and this was associated with repression of the putative miR-107
      target, cyclin-dependent kinase 6, thereby providing a functional basis for the
      epigenetic inactivation of this miRNA in pancreatic cancer.

PMID- 19407488
TI  - Expression of erythropoietin and its receptor in human renal cell carcinoma.
AB  - OBJECTIVE: To investigate the prognostic impact of erythropoietin (EPO) and EPO
      receptor (EPO-R) expression in tumour as well as serum EPO in patients with renal
      cell carcinoma (RCC). METHODS: Using immunohistochemistry, EPO and EPO-R were
      assessed in tissue microarrays from 195 RCCs. RCC type, TNM stage, nuclear grade,
      survival, EPO and haemoglobin (Hb) levels in blood were registered. RESULTS:
      Strong expression of EPO and EPO-R in tumour tissue was found in 83 and 56%,
      respectively. EPO and EPO-R expression differed between RCC types. Serum EPO and
      blood Hb did not correlate to the expression of EPO or EPO-R. A positive
      correlation was found between the expression of EPO and EPO-R (p = 0.028).
      Survival was not related to tumour EPO, whereas strong EPO-R expression indicated
      a non-significantly worse prognosis. Serum EPO correlated positively to TNM stage
      and nuclear grade and negatively to survival. A multivariate analysis showed that
      TNM stage and nuclear grade were independent prognostic factors. Tumour EPO and
      EPO-R expression as well as serum EPO added no independent prognostic
      information. CONCLUSION: No correlation between EPO or EPO-R in tumour tissue and
      serum EPO or blood Hb was found. Neither EPO, EPO-R in tumour tissue nor serum
      EPO are independent prognostic factors.

PMID- 19407489
TI  - Genetics in growth, and pituitary tumorigenesis. Preface.

PMID- 19407490
TI  - Determinants of short stature and the response to growth hormone therapy.

PMID- 19407492
TI  - The candidate gene approach to the diagnosis of monogenic disorders.
AB  - The genetic basis of many human diseases has been elucidated by the candidate
      gene approach. Mouse models of human disease, whether naturally occurring or
      derived by transgenesis, have enabled a number of disease genes to be identified.
      Such approaches have formed the basis of the identification of candidate genes
      implicated in hypothalamo-pituitary development. Nevertheless, significant
      differences exist between murine and human models of disease. Chromosomal
      deletions, duplications and translocations that are visible microscopically are
      also informative and have allowed the discovery of disease genes such as SOX2 and
      SOX3. In addition, genome-wide mapping techniques using microsatellites have led
      to the identification of genes such as GPR54, mutations of which are associated
      with hypogonadotrophic hypogonadism. Newer techniques, such as array comparative
      genomic hybridization (CGH), have enabled the detection of submicroscopic
      chromosomal imbalances. These, in turn, can also lead to the identification of
      disease genes, as has been demonstrated by the discovery of mutations in CHD7 in
      some patients with the CHARGE syndrome. Most significant, however, is the recent
      optimization of high-density whole-genome single-nucleotide polymorphism arrays,
      which provides the potential to identify many disease genes and may revolutionize
      the field of human genetics.

PMID- 19407491
TI  - Progress in genome-wide association studies of human height.
AB  - Human height (stature) is a strongly genetic trait, with up to 90% of the
      variation in height within a population determined by a combination of multiple
      inherited factors. Recent advances in genetics and genomics now permit
      comprehensive genome-wide surveys of common genetic variations in those variants
      that are associated with stature. The first such studies have borne fruit,
      identifying over 40 genetic loci that can be reproducibly shown to have an
      influence on adult height. These unbiased searches throughout the genome
      identified several loci that also harbour rare mutations responsible for more
      severe alterations in height or skeletal growth. Although the predictive value of
      the common variants thus far discovered remains low, the identification of these
      loci has led to new insights into the biology of human growth, and may help
      identify genes that underlie previously uncharacterized syndromes of abnormal
      skeletal growth.

PMID- 19407493
TI  - Epigenetics and imprinted genes: insights from the imprinted Gnas locus.
AB  - The hallmarks of epigenetics--the memory of defining earlier developmental events
      and the distinction of active and inactive genes--are exemplified by imprinted
      genes. In this article, I shall consider the imprinted Gnas locus in some detail.
      Gnas encodes the stimulatory G-protein subunit, Gsalpha, an essential
      intermediate between receptor coupling and cyclic adenosine monophosphate
      generation. It provides an excellent illustration of the pleiotropic effects of
      imprinted genes, particularly on skeletal growth and metabolism, and is a
      powerful example of the conflicting effects of imprinted genes with opposing
      patterns of imprinting. I shall describe the effects of Gsalpha deficiency in
      humans and the knowledge gained from genetic manipulation in the mouse. Finally,
      given the pervasive effects of imprinted genes, I shall discuss the likelihood
      that epigenetic deregulation, for example of imprinted genes, could contribute to
      the developmental programming of chronic adult diseases.

PMID- 19407494
TI  - Silver-Russell and Beckwith-Wiedemann syndromes: opposite (epi)mutations in 11p15
      result in opposite clinical pictures.
AB  - Progress in the identification of the (epi)genetic basis of imprinting disorders
      has provided greater insight into the central role of imprinted genes in regular
      human growth. In addition to the well-known Prader-Willi, Angelman, and Beckwith
      Wiedemann syndromes, imprinting disturbances have recently been identified in
      transient neonatal diabetes mellitus, uniparental disomy (14) syndromes and
      Silver- Russell syndrome (SRS). Among these diseases, the growth retardation
      disorder SRS is unique because it is the first human disorder associated with
      epigenetic mutations that affect two different chromosomes. In addition to
      maternal uniparental disomy of chromosome 7, hypomethylation of the imprinting
      control region 1 in 11p15 and maternal duplication of 11p15 have recently been
      described as major (epi)genetic disturbances in SRS. Interestingly, opposite
      (epi)- mutations are involved in the overgrowth disease Beckwith-Wiedemann
      syndrome (BWS). Thus SRS and BWS can be regarded as two genetically and
      clinically opposite clinical pictures. Although not yet completely understood,
      SRS and BWS can be used as models to decipher the functional link between the
      observed (epi)genetic mutations and the clinical features in individuals with
      disturbed growth. Future studies will clarify the complex basis of human growth
      and hopefully contribute to better-directed therapies.

PMID- 19407495
TI  - The growth hormone cascade and its role in mammalian growth.
AB  - The myriad actions of growth hormone (GH) are still incompletely understood,
      despite decades of research. Although it is a major regulator of post-natal
      growth in mammals, much of its effects on skeletal growth are recognized to be
      mediated indirectly, through the stimulation of production of insulin-like growth
      factor (IGF)-I, as well as some of the major serum carrier proteins for IGF-I and
      -II, such as IGF-binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS).
      The regulation of IGF-I production by GH appears to be mediated entirely by
      signalling through the Janus kinase (JAK) 2 pathway, via the phosphorylation of
      the transcription factor, signal transducer and activator of transcription (STAT)
      5b. GH also signals, however, through additional pathways that are likely to be
      critical to the metabolic actions of GH.

PMID- 19407496
TI  - Genes of importance in the hormonal regulation of growth plate cartilage.
AB  - Longitudinal bone growth occurs in the growth plate through a process in which
      resting zone chondrocytes are recruited to start active proliferation and then
      undergo differentiation, followed by apoptosis and later mineralization. Bone
      growth is controlled by a multitude of genes encoding for hormones and growth
      factors acting systemically and/or locally in the growth plate. From studies of
      individuals with a mutated aromatase gene and a male patient with defective
      oestrogen receptor (ER) alpha, it has become clear that the action of oestrogen
      is indispensable for normal pubertal growth and growth plate fusion. As new
      aromatase inhibitors and specific modulators of ERs are developed, these could
      offer more specific ways to modulate longitudinal growth and growth plate fusion.
      It is difficult to extrapolate data obtained in experimental animals, as clear
      species differences exist, emphasizing the need for new models that will allow
      studies in human growth plate cartilage.

PMID- 19407497
TI  - Network of European studies of genes in growth (NESTEGG).
AB  - The network of European studies of genes in growth (NESTEGG) is an international
      growth genomics project, focusing on the birth size phenotypes of small for
      gestational age (SGA) and idiopathic short stature. Seven hundred controls and
      1,275 cases with their parents have been recruited. Detailed clinical histories
      and auxological measurements are recorded in a clinical database. Candidate gene
      studies are being undertaken with the study DNA samples. These genetic data will
      be used to explore associations with the clinical phenotypes of short stature and
      SGA birth size, and, in a subset, response to growth hormone (GH) therapy. This
      article describes the study methodology and reviews the association of the exon 3
      deleted genotype of the GH receptor with GH responsiveness in GH-treated children
      born SGA.

PMID- 19407498
TI  - Growth hormone receptor exon 3 isoforms and their implication in growth disorders
      and treatment.
AB  - Human recombinant growth hormone (hGH) has been used to treat short stature in
      several different conditions, but considerable inter-individual variation in
      short- and long-term growth response exists. Pharmacogenomics can provide
      important insights into hGH therapy. The GH receptor (GHR) is the first key
      molecule mediating GH action. In the past 3 years, a common GHR polymorphism
      reflecting the presence (GHRfl) or absence (GHRd3) of exon 3 has been under
      intensive investigation regarding its influence on the response to hGH therapy.
      Studies that evaluated response to GH treatment determined by these two GHR
      isoforms in children with GH deficiency, girls with Turner syndrome, children
      born small for gestational age and patients with acromegaly showed that patients
      carrying the GHRd3 allele demonstrated a greater GH sensitivity than patients
      homozygous for the GHRfl allele. Other studies presented contradictory data,
      however, which may be caused by confounding factors such as small sample sizes
      and differences in experimental design. This GHR exon 3 genotype is the first
      identified genetic factor found to modulate the individual response to GH
      therapy. This article reviews the historical aspects and pharmacogenetic studies
      published to date in relation to this GHR polymorphism. The analyses of present
      and future validation studies may define the use of this and other polymorphisms
      in clinical practice, moving from pharmacogenetics to routine application and
      allowing individualization of hGH doses to optimize final outcome.

PMID- 19407499
TI  - Noonan syndrome, the Ras-MAPK signalling pathway and short stature.
AB  - Short stature, with a mean final height almost two standard deviations below the
      normal mean, is a major feature of Noonan syndrome. The biological basis of the
      growth failure is not yet clear. The recent detection of mutations in the protein
      tyrosine phosphatase, non-receptor type 11 gene (PTPN11) in half of all
      individuals with Noonan syndrome has opened up a new perspective from the
      endocrine point of view, since the tyrosine phosphatase SHP2 encoded by PTPN11 is
      implicated in the downregulation of growth hormone (GH) receptor signalling.
      Current data show decreased insulin-like growth factor (IGF)-I and IGF-binding
      protein 3 (IGFBP-3) levels in those children with Noonan syndrome who carry
      PTPN11 mutations. GH responsiveness seems to be reduced in the presence of PTPN11
      mutations, but, so far, data are too scarce to draw any final conclusions.
      Children with Noonan or Noonan-related syndromes carrying mutations in components
      of the Ras-mitogen-activated protein kinase (MAPK) signalling pathway downstream
      from SHP2 also have short stature, though less frequently in the case of SOS1
      mutations. Therefore, apart from the disturbance of GH signalling, there must be
      other relevant mechanisms that influence longitudinal growth in Noonan syndrome.
      In a small subgroup of patients with Noonan syndrome and Noonan-related
      syndromes, tumour risk is increased. This susceptibility is relevant when GH
      therapy is considered. Progress in the understanding of cell regulation by Ras
      MAPK signalling and its interconnection with other pathways will hopefully
      provide evidence on which therapy might be helpful and which might be nocuous in
      the care of children with Noonan syndrome.

PMID- 19407501
TI  - Advances in understanding pituitary adenomas.

PMID- 19407500
TI  - The future of research into growth hormone responsiveness.
AB  - Decades of experience with growth hormone (GH) therapy have indicated
      considerable variability in responsiveness to therapy, even within single
      diagnostic categories, such as GH deficiency, Turner syndrome, intrauterine
      growth retardation and idiopathic short stature. It is likely that the major
      explanation for such variability lies in the genetic composition of the patient,
      including mutations of genes participating in the GH-insulin growth factor I
      cascade and genetic polymorphisms. Future studies of pharmacogenomic and
      pharmacoproteomic markers may allow us to better predict and categorize
      responsiveness to therapy.

PMID- 19407502
TI  - Oncogene-induced cellular senescence: causal factor in the growth arrest of
      pituitary microadenomas?
AB  - Pituitary microadenomas are exceedingly common in the general population, and
      only a very few progress to a size of more than a few millimetres. The early and
      total, or near- total, growth arrest preventing the outgrowth of these adenomas
      calls to mind the phenomenon of oncogene- induced cellular senescence (OIS), a
      growth arrest response brought about by oncogenic signalling. In the past, OIS
      has been demonstrated in a variety of benign neoplastic lesions, in animal models
      as well as in man. OIS results from the activation of powerful antiproliferative
      signalling networks, and presumably acts as a protective response preventing the
      outgrowth of early neoplastic lesions that are driven by a single or a very few
      oncogenic lesions. A few recent studies on pituitary tumorigenesis in Rb+/- mice,
      as well as some preliminary observations in human pituitary adenomas, lend
      support to the idea that OIS is also an important mediator of growth arrest in
      these occult pituitary tumours. If so, the fact that over 99.9% of pituitary
      adenomas never produce clinical problems of mass effect attests to the efficacy
      of this response.

PMID- 19407503
TI  - Pituitary tumour-transforming gene (PTTG) and pituitary senescence.
AB  - Pituitary tumours account for 15% of intracranial neoplasms and are benign
      monoclonal neoplasms that may be clinically silent or secrete hormones, including
      prolactin, growth hormone, adrenocorticotrophic hormone or, rarely, thyroid
      stimulating hormone or gonadotrophins. These adenomas account for clinical
      infertility, growth disorders and hypercortisolism or metabolic dysfunctions
      associated with hypopituitarism. We explored the role of disordered pituitary
      cell proliferation control in the pathogenesis of these invariably benign
      adenomas, studying the mechanisms underlying pituitary aneuploidy, premature
      proliferative arrest (senescence), markers of cell proliferation and
      tumorigenesis in single, double or triply mutant transgenic mice with mutations
      of Rb, Pttg and/or p21. Our results provide further insights into the role of
      cell-cycle control and growth constraints on experimental and human pituitary
      tumours, which underlie their failure to progress to malignancy. These results
      improve our understanding of pituitary syndromes associated with infertility,
      growth disorders, hypercortisolism or adrenal, thyroid and gonadal failure due to
      abrogated pituitary function.

PMID- 19407504
TI  - Differential gene expression in models of pituitary prolactin-producing tumoral
      cells.
AB  - Although several genes and signalling pathways have been identified as important
      effectors in the development of pituitary tumours, our understanding of pituitary
      tumorigenesis remains incomplete and is the focus of much current research. Use
      of the mRNA differential display technique in prolactinomas from D2-receptor
      knockout mice and in stable GH3 cell line clones with enhanced tumorigenicity in
      vivo has led to the identification of two genes that are involved in the
      pathogenic process--BMP-4 and RSUME. Bone morphogenetic protein-4 (BMP-4) has
      been found to have a crucial role in prolactinoma development and also in
      signalling crosstalk with oestrogens. In contrast, BMP-4 has an inhibitory role
      in corticotrophinomas. RSUME (RWD-containing sumoylation enhancer) was identified
      from a transformed lactosomatotrophic cell line that had increased tumorigenic
      and angiogenic potential. Expression of RSUME was induced under hypoxic
      conditions and it has a potential role during vascularization. The differential
      expression and action of BMP-4 in prolactinomas and corticotrophinomas highlights
      the importance of studying a gene with contrasting actions in two cell lineages
      of the same organ in order to understand the pituitary transformation process.
      Both BMP-4 and RSUME may be interesting targets for inhibiting steps involved in
      pituitary tumorigenesis.

PMID- 19407505
TI  - G-protein and signalling in pituitary tumours.
AB  - The genesis of pituitary tumours is still under debate. Although these neoplasias
      are monoclonal in origin, mutations of GNAS1, the gene encoding the alpha subunit
      of the stimulatory G-protein, Gs, are the only mutational changes unequivocally
      associated with growth hormone (GH)-secreting adenomas. However, despite the
      growth advantage that this oncogene has been demonstrated to confer in vitro,
      patients carrying this mutation have a similar clinical and biochemical phenotype
      to those who do not carry it. This discrepancy is due to the occurrence of events
      able to counteract the biological effect of the mutation. Consistent with a
      potential role of the cyclic adenosine monophosphate pathway in the proliferation
      of somatotrophs, germline mutations of the gene encoding the type 1alpha
      regulatory subunit of protein kinase A (PRKAR1A) have been found in patients with
      the Carney complex, a syndrome including GH-secreting adenomas, whereas
      alterations in the expression levels of this subunit are frequently observed in
      sporadic adenomas.

PMID- 19407507
TI  - Genetic, molecular and clinical features of familial isolated pituitary adenomas.
AB  - Pituitary adenomas occur in a familial setting in about 5% of all cases, and over
      half of these are due to multiple endocrine neoplasia type 1 (MEN1) and Carney's
      complex (CNC). Non-MEN1/CNC familial pituitary tumours of all tumour phenotypes,
      known as familial isolated pituitary adenomas (FIPA), were first described in the
      late 1990s. Clinical features of FIPA differ from those of sporadic pituitary
      adenomas, as patients with FIPA have a younger age at diagnosis and larger
      tumours. About 15% of patients with FIPA have mutations in the aryl hydrocarbon
      receptor-interacting protein gene (AIP), which indicates that FIPA may have a
      diverse genetic pathophysiology. This article describes the clinical features of
      FIPA, the tumour pathologies found in this setting and the genetic/molecular data
      that have recently been reported in FIPA.

PMID- 19407508
TI  - Recent clinical and pathophysiological advances in non-functioning pituitary
      adenomas.
AB  - Pituitary adenomas are being recognized and diagnosed with increasing frequency.
      One of the most common forms of pituitary lesion is the clinically non
      functioning pituitary adenoma (NFPA), which is often diagnosed incidentally. The
      vast majority of pituitary adenomas are sporadic, but familial adenomas can occur
      in the multiple pituitary adenoma type 1 syndrome, in Carney complex or in
      familial isolated pituitary adenoma. Distinguishing NFPA from prolactinomas can
      occasionally cause a differential diagnostic problem due to the 'stalk effect'.
      NFPA often show hormone synthesis on tissue immunostaining without causing
      clinical symptoms. Most often these are silent gonadotroph adenomas, with silent
      corticotroph or somatotroph adenomas occurring less frequently. It is unclear why
      these silent adenomas do not release hormones at a clinically recognizable level,
      although it is probable that there is a continuum between fully functional and
      completely silent adenomas. Another intriguing feature of NFPAs is the lack of
      clinical response to somatostatin analogues, despite the presence of somatostatin
      receptors and an often good response in the in vitro setting. Temozolomide has
      been successfully used for the treatment of a few aggressive pituitary adenomas,
      and the response to this drug could be influenced by the expression of the DNA
      repair enzyme O-6-methylguanine DNA methyltransferase. The early diagnosis,
      prediction of long-term outcome and treatment of NFPAs remain a challenge for
      endocrinologists.

PMID- 19407506
TI  - Genetics, gene expression and bioinformatics of the pituitary gland.
AB  - Genetic cases of congenital pituitary hormone deficiency are common and many are
      caused by transcription factor defects. Mouse models with orthologous mutations
      are invaluable for uncovering the molecular mechanisms that lead to problems in
      organ development and typical patient characteristics. We are using mutant mice
      defective in the transcription factors PROP1 and POU1F1 for gene expression
      profiling to identify target genes for these critical transcription factors and
      candidates for cases of pituitary hormone deficiency of unknown aetiology. These
      studies reveal critical roles for Wnt signalling pathways, including the TCF/LEF
      transcription factors and interacting proteins of the groucho family, bone
      morphogenetic protein antagonists and targets of notch signalling. Current
      studies are investigating the roles of novel homeobox genes and pathways that
      regulate the transition from proliferation to differentiation, cell adhesion and
      cell migration. Pituitary adenomas are a common human health problem, yet most
      cases are sporadic, necessitating alternative approaches to traditional Mendelian
      genetic studies. Mouse models of adenoma formation offer the opportunity for gene
      expression profiling during progressive stages of hyperplasia, adenoma and
      tumorigenesis. This approach holds promise for the identification of relevant
      pathways and candidate genes as risk factors for adenoma formation, understanding
      mechanisms of progression, and identifying drug targets and clinically relevant
      biomarkers.

PMID- 19407517
TI  - Pregnancy termination. Foreword.

PMID- 19407509
TI  - The MEN1 gene and pituitary tumours.
AB  - Sporadic multiple endocrine neoplasia type 1 (MEN1) is defined as the occurrence
      of tumours in two of three main endocrine tissue types: parathyroid, pituitary
      and pancreaticoduodenal. A prolactinoma variant or Burin variant of MEN1 was
      found to occur in three large kindreds, with more prolactinomas and fewer
      gastrinomas than typical MEN1. MEN1 tumours differ from common tumours by showing
      features from the MEN1 gene (e.g. larger pituitary tumours). They also show
      various expressions of tumour multiplicity; however, pituitary tumour in MEN1 is
      usually solitary. Diagnosis in MEN1 carriers during childhood is not directed at
      cancers but at benign morbid tumours. Morbid prolactinoma occurred at the age of
      5 years in one MEN1 individual; hence, this is the earliest age at which to
      recommend tumour surveillance in carriers. The MEN1 gene shows biallelic
      inactivation in 30% of some types of common variety endocrine tumours (e.g.
      parathyroid adenoma, gastrinoma, insulinoma and bronchial carcinoid), but in only
      1-5% of common pituitary tumours. Heterozygous knockout of MEN1 in mice provides
      a robust model of MEN1 and has been found to support further research on anti
      angiogenesis therapy for pituitary tumours. The rarity of MEN1 mutations in some
      MEN1-like states aids the identification of other mutated genes, such as AIP,
      HRPT2 and p27(Kip1). We present recent clinical and basic findings about the MEN1
      gene, particularly concerning hereditary vs. common variety pituitary tumours.

PMID- 19407518
TI  - Trends in abortion in the United States.
AB  - The US abortion rate peaked soon after 1973, remained fairly constant through the
      1980s, and began a steady decline to 2005. A substantial drop in the abortion
      rates of teenagers and women ages 20 to 24 accounts for much of the decline from
      1989 to 2004. All race and ethnic groups experienced declines in abortion rates
      over the past 30 years, but the rate of black, and to a lesser extent Hispanic,
      women remains higher than that of non-Hispanic whites. The number of abortion
      providers has declined in recent decades, but the introduction of early medical
      abortion may have slowed this trend.

PMID- 19407519
TI  - What physicians need to know about the legal status of abortion in the United
      States.
AB  - Abortion is the most politically contested social issue in the United States, a
      debate that manifests itself in extensive regulation of abortion as a health care
      service. This study provides a brief history of the judicial acceptance of
      abortion regulation and an overview of the most common forms of abortion
      regulation affecting physicians in the United States. The article concludes with
      a discussion of pending threats to the legal right to abortion in the United
      States and recommended resources where physicians can find assistance to comply
      with existing laws.

PMID- 19407520
TI  - Medication abortion.
AB  - Medical methods for pregnancy termination in early gestation offer women an
      alternative to surgical evacuation and have the potential to improve access
      globally to safe abortion. Several drug regimens are used with varying efficacy
      including mifepristone plus misoprostol, misoprostol alone, and methotrexate plus
      misoprostol. Where available, a mifepristone plus misoprostol regimen is most
      frequently used and is highly effective for early abortion. We review these drug
      regimens along with clinical practice recommendations including patient
      counseling and selection, regimen administration location, expected side effects,
      and follow-up procedures. Overall, women who choose medical abortion report high
      levels of satisfaction.

PMID- 19407521
TI  - First trimester surgical abortion.
AB  - First trimester surgical abortion is a very common, effective, and safe
      procedure. When a woman presents requesting pregnancy termination, counseling
      regarding pregnancy options and procedural risks, as well as a careful
      preoperative assessment are vital to a successful outcome. If a patient decides
      to undergo a surgical abortion, either an electric or manual vacuum aspiration
      may be performed, based upon provider preference. Complications of first
      trimester surgical abortion occur in only 0.5% of all cases and include: failed
      abortion, incomplete abortion, hematometria, hemorrhage, infection, and uterine
      perforation.

PMID- 19407522
TI  - Analgesia/pain management in first trimester surgical abortion.
AB  - Management of pain during abortion is a critical aspect of patient care. Although
      it is not always possible to offer a range of pain control options in every
      setting, individualizing pain medications as much as possible for patients'
      preferences is likely to improve satisfaction with the abortion experience.
      Evidence suggests that higher volume (at least 200 mg lidocaine) and deeper
      injections are beneficial for cervical block. Adding intravenous sedation with a
      moderate dose of fentanyl and midazolam reduces the pain scores. Oral
      benzodiazepines may improve satisfaction and anxiety. Deep sedation and general
      anesthesia are important options for women with significant medical conditions or
      complicated procedures.

PMID- 19407523
TI  - Cervical dilation in second-trimester abortion.
AB  - Dilation and evacuation, the most common method performed for second-trimester
      abortion in the United States, requires sufficient cervical dilation to reduce
      the risk of complications such as cervical laceration or uterine perforation. The
      cervix may be prepared with osmotic dilators such as laminaria, Lamicel, or
      Dilapan-S, or with pharmacologic agents such as misoprostol. Dilapan-S and
      Lamicel achieve their maximum dilation faster than laminaria, making same-day
      procedures possible. Misoprostol has limited data supporting its use in this
      setting. Decisions regarding which method is best are clinician-dependent, and
      factors such as gestational age and time allowed for preparation should be
      considered.

PMID- 19407524
TI  - Second-trimester surgical abortion.
AB  - Surgical abortion in the second trimester became popularized in the 1970s, and
      now accounts for the majority of abortion procedures performed in this country.
      Dilation and evacuation is the most commonly used method in the second trimester,
      but dilation and curettage can be used with earlier gestations, and intact
      dilation and extraction accounts for a minority of later procedures. These
      various procedures will be addressed in detail. Other considerations such as
      preoperative and intraoperative use of ultrasound, use of uterotonics, pain
      management, appropriate location for second-trimester abortion provision, and
      routine postoperative care will also be reviewed.

PMID- 19407525
TI  - Second-trimester induction of labor.
AB  - Second-trimester abortions are most commonly performed in the United States via
      dilation and evacuation; however, there are instances in which the use of
      systemic abortifacients is necessary. Lack of trained staff to perform late
      abortion procedures, fetal anomalies, and patient preference are important
      considerations when selecting the method of termination. Second-trimester
      abortions with misoprostol-only protocols require higher doses, side effects are
      more common, and the time to complete the abortion is longer in comparison to
      mifepristone-misoprostol combinations. Feticidal agents are recommended to avoid
      transient fetal survival. This chapter will review medical induction methods
      between gestational ages of 14 and 24 weeks that are commonly used in the United
      States.

PMID- 19407527
TI  - Complications of surgical abortion.
AB  - Surgical abortion is one of the most common procedures performed in reproductive
      aged women and when performed by a skilled provider in the appropriate setting,
      it is one of the safest surgeries. Though the risk of complications is low, it
      increases exponentially with gestational age. Factors increasing risk of
      morbidity may be demographic, such as increasing patient age; medical, such as
      prior cesarean delivery; and procedural, such as inadequate dilation. This
      chapter will provide information on how to recognize factors that increase risk,
      steps to minimize risk, and to identify and manage complications promptly.

PMID- 19407526
TI  - Infectious complications of pregnancy termination.
AB  - Infectious complications are a significant source of morbidity and mortality
      associated with pregnancy termination worldwide. However, in areas where abortion
      practices are legal, the risk of infection is very low. Proper technique,
      prophylaxis, and initial management of septic abortion have led to a significant
      decrease in risk of serious complications such as sepsis and death. Clinical
      features, management, and prevention of postabortal infection will be reviewed in
      the setting of legalized abortion.

PMID- 19407528
TI  - Obstetric practice in the third world. Foreword.

PMID- 19407529
TI  - Maternal mortality: an enduring epidemic.
AB  - Women continue to die from pregnancy-related causes at an alarming rate. Maternal
      mortality was first called a neglected epidemic in 1985, but to date, no
      significant improvements have been realized. Great disparity exists as lifetime
      risk of dying from pregnancy is 1 in 26 in Africa, 1 in 7300 in high-income
      areas. The UN Millennium Development Goals call for a 75% reduction in maternal
      mortality by 2015, which will only be realized when priority setting, funding,
      and program implementation can create conditions for appropriate human resources,
      infrastructure, and patient education for high-quality obstetric care.

PMID- 19407530
TI  - Saving mother's lives: programs that work.
AB  - Maternal mortality is a complex problem requiring complex responses.
      Nevertheless, every intervention must operate through one of 3 pathways:
      preventing pregnancy, preventing complications, or preventing death when
      obstetric complications occur. We describe interventions following each pathway
      and assess their evidence base. In general, the more specific the intervention
      (such as procedures) the stronger the evidence. Broad interventions ("programs"
      for example) have a weaker evidence base although evidence is accumulating. The
      potential for robust evidence for effective programs is limited by epidemiologic
      design-the logistic difficulties of randomization, blinding, and single impact
      variables.

PMID- 19407531
TI  - Ethical and social issues facing obstetricians in low-income countries.
AB  - A review of publications on ethical and social issues from low-income countries
      was done with the aim of highlighting the major ethical and social issues facing
      obstetricians in these countries. Low-income countries were identified using the
      World Health Organization income group classification of member nations.
      Obstetricians in low-income countries face a wide range of special social and
      ethical issues that reflect the peculiarities of their practice environment
      characterized by poverty, low education, deep attachment to tradition and
      culture, low social status of women, and high levels of physician's paternalism.

PMID- 19407532
TI  - Obstetric ultrasonography in low-income countries.
AB  - The major issues in obstetric practice in developing countries are the high rates
      of maternal and perinatal mortality. In most low-income countries health
      financing systems are not well established so most people pay for health services
      at the service delivery points. This causes cost-related issues to be of major
      concern. The main questions that therefore need to be addressed about obstetric
      ultrasonography in low-income countries is whether the practice improves maternal
      and neonatal outcomes and whether the service is within the means of most people
      in these countries. The indications for obstetric ultrasound, guidelines for the
      use of obstetric ultrasound and the benefits of obstetric ultrasound in low
      income countries are discussed and the future of obstetric ultrasound in
      developing countries is also briefly considered.

PMID- 19407533
TI  - The partograph for the prevention of obstructed labor.
AB  - Obstructed labor is an important cause of maternal and perinatal mortality and
      morbidity. The partograph graphically represents key events in labor and provides
      an early warning system. The World Health Organization partographs are the best
      known partographs in low resource settings. Experiences with World Health
      Organization and other types of partographs in low resource settings suggest that
      when used with defined management protocols, this inexpensive tool can
      effectively monitor labor and prevent obstructed labor. However, challenges to
      implementation exist and these should be addressed urgently.

PMID- 19407534
TI  - The obstetric face and challenge of HIV/AIDS.
AB  - The human immunodeficiency virus (HIV) pandemic is one of the most serious health
      crises facing the world. Of the estimated 33.2 million people living with HIV
      worldwide, 22.5 million (68%) live in Sub-Saharan Africa, where women of
      childbearing age are most severely affected. Children primarily acquire HIV
      infection through mother-to-child transmission. Despite recent encouraging
      success, low-income countries have not been able to effectively curtail
      transmission of HIV to the infant during or after pregnancy, resulting in about
      90% of the estimated 420,000 newly infected children per annum occurring in Sub
      Saharan Africa.

PMID- 19407535
TI  - Challenges in managing postpartum hemorrhage in resource-poor countries.
AB  - Managing postpartum hemorrhage depends in part on having a prepared mind, a
      complement of trained coworkers, and full access to modern therapies. The last 2
      components are rare in resource-poor areas and their absence may be accentuated
      by climatic instability and lack of basic transportation. Greater use of the
      active management of third stage of labor and administration of misoprostol by
      nontrained birth attendants will provide beneficial reductions in hemorrhage
      rates in resource-poor areas. Additional improvements depend on increasing public
      awareness, facilitating existing nongovernmental organizations in their community
      related, upgrading training of traditional birth attendants, and providing cell
      phone communication to workers in remote areas, in addition to providing better
      access to blood.

PMID- 19407550
TI  - ASTEC in the Spotlight: Opening the IJGC Forum.

PMID- 19407551
TI  - Surveillance procedures for patients for cervical carcinoma: a review of the
      literature.
AB  - Cervical cancer is still one of the most common malignancies in women. Treatment
      for cervical cancer is very successful, especially in early stage. However, some
      patients will experience recurrence. Primary purpose of follow-up programs is
      early detection of recurrence disease that should be more likely to be amenable
      to treatment, thereby improving the clinical outcome. Although, in the
      literature, most studies have shown that the surveillance programs did not
      improve the clinical outcome of patients with diagnosis of recurrence, this
      clinical practice is regarded as traditional management. The use of Papanicolaou
      tests to detect recurrent cervical cancer is not sufficiently justified. The
      assessment of tumor markers such as squamous cell carcinoma antigen could be
      useful. Imaging techniques are important for the detection and assessment of
      recurrent disease. The role of chest radiographs to detect asymptomatic
      recurrence in patients treated for cervical carcinoma remains controversial.
      Detection of a new abnormal mass or the changes in the size of a known lesion
      caused by cancer growth and the determination of the extent of recurrence with
      computed tomography and magnetic resonance imaging may provide clinical
      assistance in selection of optimal therapy. The fluoro-2-deoxy-glucose-positron
      emission tomography for surveillance only shows 80% of specificity and accuracy
      with negative predictive value of 100%. Integrated fluoro-2-deoxy-glucose
      positron emission tomography/computed tomography provides precise anatomic
      localization of suspicious areas and therefore a better diagnostic interpretation
      with a possible impact on disease-free survival as well. In conclusion, our
      review confirms the need of prospective studies to compare the effectiveness of
      different follow-up regimens measuring as outcome overall survival and quality of
      life parameters.

PMID- 19407552
TI  - Management of recurrent endometrioid endometrial carcinoma: an overview.
AB  - In this paper, an overview of the literature on the management of recurrent
      endometrial cancer is presented, focusing on patients with histopathologic
      endometrioid type of tumors. The different treatment modalities are described,
      and a management recommendation scheme is presented. Indications for surgical
      treatment depend on resectability, site and size of the tumor, and performance
      status of the patient. Indications for radiotherapy depend on the site of the
      recurrence and also on the initial therapy received. When considering systemic
      treatment for patients with recurrent endometrial cancer, it is important to take
      into account the general health status and condition of the patient as well as
      which prior therapy the patient has received. The treatments of choice for
      patients with hormone-sensitive tumors (positive receptor levels, low-grade
      tumors, and long disease-free interval) are progestagens as first-line treatment
      and tamoxifen as second-line treatment. Patients with high-grade tumors, negative
      hormone receptor levels, and short treatment-free interval are best treated with
      chemotherapy. Paclitaxel, doxorubicin, and cisplatin are the most active
      combination therapy for these patients but with significant toxicity. In phase II
      studies, the combination therapy with paclitaxel and carboplatin seems to be as
      effective but less toxic and can be administered in outpatient clinic. The
      literature on the management of patients with recurrent endometrial cancer is
      discussed in detail. The different sites of recurrent disease (ie, local,
      regional, and/or distant) are evaluated separately; management recommendations
      are proposed, and alternative approaches are given.

PMID- 19407553
TI  - Prediction of human papillomavirus 16 e6 gene expression and cervical
      intraepithelial neoplasia progression by methylation status.
AB  - INTRODUCTION: Human papillomavirus (HPV) infection represents the most important
      risk factor for the development of cervical intraepithelial neoplasia (CIN) and
      cervical cancer. We aimed to analyze the consequences of methylation of the E6
      gene promoter in distinct stages of HPV-16-induced cellular transformation to
      assess its importance for disease progression. METHODS: Human papillomavirus 16
      was detected by sensitive polymerase chain reaction (PCR). Determination of E6
      gene promoter methylation was analyzed by digestion with specific restriction
      endonuclease McrBC followed by PCR amplification. Expression of the E6 gene was
      determined by quantitative real-time PCR. RESULTS: Of 103 cervical smears from
      asymptomatic women with no cytological and colposcopic abnormalities, 20.4% were
      HPV-16-positive. Human papillomavirus 16 was present in 44.4% of 18 patients with
      CIN I, in 62.2% of 143 patients with CIN II/III, and in 74.2% of 31 cervix
      carcinoma specimens. The incidence of HPV-16 in all lesions compared with
      asymptomatic women was statistically significant (P < 0.001, Pearson chi test).
      Methylation was detected in 81% (n = 21) of HPV-16-positive asymptomatic smears
      compared with 62.5% in CIN I (n = 8), 31.5% (n = 89) in CIN II/III, and 43.4% (n
      = 23) in carcinomas; a statistical significance between lesions and healthy women
      was found (P < 0.001, Pearson chi test). Expression of E6 mRNA correlated with
      methylation status (P = 0.010, Mann-Whitney U test). CONCLUSIONS: We conclude
      that methylation of the E6 gene promoter in HPV-16 genome is a predictive
      biomarker for cervical cancer progression by regulating the expression of the E6
      oncogene.

PMID- 19407554
TI  - Proteomics reveals protein profile changes in cyclooxygenase-2 inhibitor-treated
      endometrial cancer cells.
AB  - OBJECTIVE: To examine effects of an inhibitor of cyclooxygenase (COX)-2, NS-398,
      on the proliferation, apoptosis and invasion characteristics of endometrial
      cancer cell RL95-2. METHODS: (1) Western blotting was carried out to determine
      COX-2 protein expression in RL95-2 cells and normal endometrium specimens. (2)
      The effect of NS-398 treatment on the cell proliferation, apoptosis, and invasion
      was assessed by methyl thiazolyl tetrazolium assay, flow cytometry, and matrigel
      invasion assay, respectively. (3) Finally, the proteomic analysis was used to
      find out proteins that are differentially expressed because of NS-398 treatment.
      RESULTS: (1) COX-2 protein in RL95-2 cell line was significantly higher than that
      in normal endometrium. (2) NS-398 had significant growth inhibition effects on
      RL95-2 cells in a dose- and time-dependent manner. (3) NS-398 increased the
      proportion of cells in G1 and decreased the proportion of cells in the G2 phase
      in RL95-2 cells. (4) NS-398 could restrain endometrial cancer cells invasion. (5)
      The proteomic analysis revealed several proteins that are differentially
      expressed because of NS-398 treatment; the down-regulated proteins identified are
      hnRNP K, alpha enolase, Hsp70, tropomyosin, and protein disulfide isomerase, the
      up-regulated protein is phosphatidylethanolamine binding protein. CONCLUSIONS:
      The expression of COX-2 plays an important role in tumorigenesis of endometrial
      cancer. NS-398 can inhibit the ability of RL95-2 cell proliferation, viability,
      and invasion. In this study, the well-resolved reproducible 2-DE maps of NS-398
      treated and control RL95-2 cells were established, and the significantly
      different expressed proteins are preliminary identified.

PMID- 19407555
TI  - Exposure of mcf-7 breast cancer cells to electromagnetic fields up-regulates the
      plasminogen activator system.
AB  - Effects of electromagnetic fields (EMFs) on the incidence of breast cancer (BC)
      have been proposed by a number of epidemiological studies. The molecular
      mechanism of the impact of EMFs on cells is not yet clear, although changes in
      gene expression have been reported in various cellular systems. In this
      investigation, the interference of low-frequency EMFs with the plasminogen
      activator system was examined in BC cells.MCF-7 BC cells from 2 different sources
      were exposed to highly homogeneous 50-Hz EMFs. Changes in gene expression were
      analyzed by reverse transcriptase-polymerase chain reaction.In MCF-7 cells
      exposed to 1.2 microT EMF expression of the urokinase plasminogen activator gene
      and of plasminogen-activator inhibitor-1 was markedly increased. The expression
      of the receptor for urokinase plasminogen activator was only marginally increased
      in 1 of the 2 tested cell lines and expression of the tissue plasminogen
      activator was at least slightly down-regulated in BC cells exposed to EMFs.EMFs
      may be able to increase the metastatic potential of breast tumors. The use of our
      newly established exposure system for EMFs may allow us to study the signaling
      processes involved in the induction of a metastatic phenotype of breast cancer
      cells.

PMID- 19407556
TI  - Expression status and mutational analysis of the PTEN and P13K subunit genes in
      ovarian granulosa cell tumors.
AB  - Granulosa cell tumors (GCT) are a unique subset of ovarian tumors which have a
      molecular phenotype resembling that of follicle stimulating hormone (FSH)
      stimulated pre-ovulatory granulosa cells. FSH acts via its receptor to stimulate
      signaling pathways including the phosphatidylinositol 3-kinase (PI3K)-AKT
      pathway. Activation of this pathway occurs in solid tumors, including ovarian
      epithelial tumors, through mutation of the PI3K subunit genes or inactivation of
      the tumor suppressor, PTEN. Activation of this pathway would be predicted to be
      tumorigenic in granulosa cells.Expression of the 2 PI3K subunit genes, PIK3CA,
      which encodes the catalytic subunit, and PIK3R1, which encodes the regulatory
      subunit, together with the PTEN gene was determined in a panel of GCT, 2 human
      GCT-derived cell lines, COV434 and KGN, and normal ovary. Direct sequence
      analysis was used to screen for mutations. Expression of all 3genes was observed
      in the GCT without evidence of overexpression for the PI3K subunit genes or loss
      of expression for PTEN. Sequence analysis of amplicons spanning exons 9and 20, in
      which greater than 75% of mutations occur in the PIK3CA gene did not identify any
      missense mutations. Similarly, the previously reported deletions in exons 12 and
      13 of the PIK3R1 were not found in the GCT. Three amplicons spanning the entire
      coding sequence of the PTEN gene were sequenced; neither deletions nor mutations
      were identified.These findings suggest that activation of PI3K signaling through
      PI3K/PTEN mutation or altered expression, in contrast to many other types of
      solid tumor, is not associated with GCT.

PMID- 19407557
TI  - Is there a taxane-free interval that predicts response to taxanes as a later-line
      treatment of recurrent ovarian or primary peritoneal cancer?
AB  - OBJECTIVES: Taxanes have reported response rates of 20% to 40% in recurrent
      ovarian cancer (ROC) but are less well studied as a later-line treatment. We
      reviewed our experience with taxanes in ROC to determine (1) if a taxane-free
      interval is associated with response rates in women with ROC and (2) if the use
      of intervening therapy (IT) affects subsequent response rates to taxanes.
      METHODS: We retrospectively identified women who received first- or second-line
      platinum-taxane therapy and later received a single-agent taxane. Demographics,
      intervening regimens, and follow-up and survival data were collected. Responses
      were characterized by cancer antigen 125 levels based on the Gynecologic Cancer
      InterGroup serologic response definitions. RESULTS: We identified 46 women who
      met the eligibility criteria. The median age was 57 years (range, 39-78 years).
      The median interval between taxanes was 25.8 months (range, 2.9-85.5 months),
      with 10 (21%) of the women were treated 12 months or less from their last taxane
      and 37 (79%) treated more than 12 months. The median number of IT was 2 (range, 0
      5). Forty patients (87%) received paclitaxel; 6 (13%) received docetaxel. All
      patients treated 12 months or less from their last taxane responded (P = 0.02).
      The number of IT was associated with a better response; all women (100%) treated
      who had no IT, 7 (54%) of 13 women with 1 to 2 ITs, and 7 (39%) of 18 women with
      3 ITs or more responded. The overall survival was 13.4 months in responders
      versus 10.6 months in nonresponders (P = 0.27). CONCLUSIONS: Taxanes maintain an
      activity as a later-line agent, even with 3 or more intervening therapies.
      However, the highest responses were seen if taxanes were used within 12 months of
      the last platinum-based combination. The lack of an increased response with
      aprolonged taxane-free interval is likely related to the number of IT, consistent
      with the emergence of multidrug resistance.

PMID- 19407558
TI  - Clinical management of ovarian small-cell carcinoma of the hypercalcemic type: a
      proposal for conservative surgery in an advanced stage of disease.
AB  - Ovarian small-cell carcinoma of the hypercalcemic type is a rare and highly
      malignant tumor. In two thirds of the patients, the tumor is associated with
      asymptomatic paraneoplastic hypercalcemia. The diagnosis may be impeded; the
      tumor must be distinguished from other tumors with similar features.This tumor
      occurs predominantly in young women and is merely lethal. The 1-year survival is
      solely 50%, with an overall 5-year survival rate of approximately 10%. It is
      believed that the empirical treatment characterized by combination of radical
      surgery, chemotherapy, and radiotherapy results in the most favorable outcome in
      terms of survival. However, the outcome remains extremely poor despite this
      aggressive approach.Alternatively, these poor survival rates may justify a less
      aggressive fertility sparing approach without compromising the outcome. Such an
      approach is illustrated by a case report involving a patient with ovarian small
      cell carcinoma of the hypercalcemic type, FIGO stage IIIC. A fertility-sparing
      approach was used, consisting of conservative surgery followed by induction
      chemotherapy, interval debulking surgery, and local radiotherapy. During follow
      up of 60 months, there was no evidence of disease and the normal menstrual cycle
      resumed.In addition to this case report, histopathological features, different
      therapeutic modalities, and outcome of ovarian small-cell carcinoma of the
      hypercalcemic type is reviewed. This report suggests that a fertility-sparing
      approach may be just as feasible as the generally applied aggressive approach.

PMID- 19407559
TI  - Preoperative diagnosis of ovarian malignancy: preliminary results of the use of 3
      dimensional vascular ultrasound.
AB  - OBJECTIVE: To estimate the accuracy of 3-dimensional (3D) vascular ultrasound in
      the preoperative assessment of pelvic masses for malignancy. METHODS: We
      performed a chart review of 66 patients who underwent 3D ultrasound for pelvic
      masses. Each mass was preoperatively judged to be benign or malignant based upon
      a study of vascularity within an ovarian mass using 3D ultrasound. Masses with
      orderly vascular architecture were categorized as probably benign, and masses
      with chaotic vascular patterns were categorized as malignant. The predictive
      value of 3D vascular ultrasound was compared with that of 2-dimensional
      ultrasound and cancer antigen 125 as a predictor of malignancy. RESULTS: Among
      the 66 patients examined, 34 underwent a documented surgical intervention. Of
      those 34 patients, 10 had primary malignant neoplasms including 2 with low
      malignant potential tumors. Suspicious 3D vascular ultrasound findings predicted
      malignant neoplasm in 10 patients. Two patients had recurrent cancer; however,
      only 1 had a suspicious ultrasound finding. There was 1 case of a low-malignant
      potential tumor without a suspicious ultrasound finding. Excluding the recurrent
      cancers and the observed patients, the positive predictive value (PPV) and the
      negative predictive value (NPV) of 3D vascular ultrasound were 100% and 95%,
      respectively. The PPV and the NPV of 2-dimensional ultrasound in predicting
      malignancy were 37% and 100%, respectively. An abnormal level of cancer antigen
      125 had a PPV and an NPV of 73% and 83%, respectively, in this patient
      population. CONCLUSIONS: In this preliminary and observational study, 3D
      ultrasound examination of vascular architecture was discriminatory in
      distinguishing benign ovarian masses from malignancy. Chaotic vascular
      architecture correlated with malignancy in this group of high-risk patients.

PMID- 19407560
TI  - Epithelial ovarian cancer: role of pegylated liposomal Doxorubicin in prolonging
      the platinum-free interval and cancer antigen 125 trends during treatment.
AB  - BACKGROUND: Epithelial ovarian cancer's response to platinum retreatment depends
      on the duration of response to first-line platinum therapy. Platinum-free
      interval predicts subsequent platinum sensitivity and is a prognostic factor.
      Little has been published on the effect of pegylated liposomal doxorubicin (PLD)
      in the prolongation of treatment-free interval. METHODS: Patients treated with
      PLD were reviewed to assess response to platinum retreatment after PLD and to
      establish the use of cancer antigen 125 (Ca125) trends. All patients treated with
      PLD had progressed within 12 months of prior platinum therapy. Cancer antigen 125
      fluctuations were categorized as the variances from the baseline (+/-10%, +/-10%
      25%, and >25%). The response to chemotherapy was defined as Ca125 reduction from
      the baseline of more than 50%, clinical, or radiological response. RESULTS: Fifty
      nine women were identified. The response rate (RR) to PLD was 28.9%, and the
      median overall survival from PLD initiation was 62 weeks. The number of women
      demonstrating more than 25% reduction in Ca125 from the baseline increased
      progressively with each cycle; at cycle 2, 11%; cycle 3, 18%; cycle 4, 22%; and
      cycle 5, 27% (trend significant between cycles 2 and 4, P = 0.004). Fifteen
      patients were re-treated with platinum after progression after PLD with 80%
      (12/15) of the patients responding. The RR to platinum retreatment after PLD
      compares favorably with the historical data on the response to second-line
      platinum retreatment. CONCLUSIONS: The sole use of early Ca125 trends in PLD
      treatment before cycle 4 may result in an erroneous discontinuation of PLD in
      potential responders. Retreatment with platinum after PLD may yield a good RR in
      selected patients even those with disease progression within 12 months after
      prior platinum treatment.

PMID- 19407561
TI  - Are surveillance procedures of clinical benefit for patients treated for ovarian
      cancer?: A retrospective Italian multicentric study.
AB  - The aim of this retrospective investigation was to assess the pattern of failures
      of 412 patients with recurrent ovarian cancer followed up with different
      surveillance protocols.Time to recurrence was less than 6 months in 98 women
      (23.8%), 6 to 12 months in 102 women (24.7%), and more than 12 months in 212
      women (51.5%). Symptoms at relapse were referred by 81 women (19.7%). Among the
      331 asymptomatic patients, the surveillance procedure that raised the suspect of
      recurrent disease was clinical examination in 49 (14.8%), imaging technique in 90
      (27.2%), serum CA 125 in 77 (23.3%), and both serum CA 125 and imaging technique
      in 115 (34.7%). At univariate analysis, survival from initial diagnosis was
      related to stage (P = 0.004), residual disease after initial surgery (P <
      0.0001), time to recurrence (P < 0.0001), site of relapse (P = 0.04), and
      treatment at recurrence (P < 0.0001), and survival after recurrence was related
      to stage (P = 0.01), residual disease (P < 0.0001), time to recurrence (P <
      0.0001), and treatment at recurrence (P < 0.0001). Conversely, symptoms at
      recurrence had no prognostic relevance. Cox proportional hazards model showed
      that residual disease and time to recurrence were the only independent prognostic
      variables for both survival from initial diagnosis (P < 0.0001) and survival
      after recurrence (P < 0.0001). In conclusion, there was no survival difference
      between asymptomatic and symptomatic patients at the time of relapse, and
      therefore, the diagnostic anticipation allowed by a scheduled follow-up protocol
      did not seem to improve the clinical outcome of patients who ultimately developed
      recurrent disease.

PMID- 19407562
TI  - RAD001 (Everolimus) Can prevent tamoxifen-related endometrial and stromal
      hyperplasia.
AB  - The mechanism of tamoxifen-associated endometrial hyperplasia and cancer is not
      elicited. RAD001 inhibits a target protein in phosphatidyl kinase pathway, which
      is involved in endometrial hyperplasia and cancer. We investigated whether
      endometrial hyperplasia can be prevented through inhibition of the target of
      rapamycin by RAD001. Sixty BALB/c mice underwent oophorectomy and were divided
      into 6 groups: group 1, placebo group; group 2, tamoxifen-treated (4 mg/kg per 24
      hours); group 3, estradiol-treated (4 mg/kg per 24 hours); group 4, RAD001
      treated (1.5 mg/kg per 24 hours); group 5, tamoxifen (4 mg/kg per 24 hours)-and
      RAD001 (1.5 mg/kg per 24 hours)-treated; and group 6, estradiol (4 mg/kg per 24
      hours)-and-RAD001 (1.5 mg/kg per 24 hours)-treated. The count of glands, the
      length of epithelium, and immunohistochemical staining of proliferating cell
      nuclear antigen were analyzed. The count of total glands and the epithelial
      length were 30.8 (7.1) and 126 (43.4) microm, 53 (8.1) and 162.5 (34.8) microm,
      65.2 (13.6) and 401.4 (44.0) microm, and 82.0 (5.2) and 444.7 (57.8) microm in
      the placebo-, the RAD001-, the tamoxifen-, and the estradiol-treated groups,
      respectively (P < 0.05). Although addition of RAD001 to estradiol did not
      decrease the count of total glands and the epithelial length, addition of RAD001
      to tamoxifen did (43.3 [13.3] and 218.0 [29.2] microm, P < 0.05). The
      immunoreactive score of proliferating cell nuclear antigen is significantly
      decreased by the addition of RAD001 to either tamoxifen or estradiol in the
      epithelial and glandular cells. RAD001 can prevent tamoxifen-associated and
      estrogen-related endometrial hyperplasias in mice. RAD001 also decreases stromal
      cell proliferation in the tamoxifen-treated mice.

PMID- 19407563
TI  - Should preoperative pathology be used to select patients for surgical staging in
      endometrial cancer?
AB  - INTRODUCTION: The decision to offer surgical staging in endometrial cancer is
      often based on preoperative histology and grade from endometrial biopsy or
      dilatation and curettage. The primary objective of this study was to evaluate the
      concordance between preoperative and final pathology from a population-based
      study of endometrial cancer to address whether preoperative biopsy is a reliable
      determinant in selecting patients for surgical staging. METHODS: Retrospective
      cohort study in Ontario, Canada, from 1996 to 2000. The study included all women
      with a preoperative diagnosis of endometrioid adenocarcinoma on endometrial
      biopsy or dilatation and curettage, followed by definitive surgery. All other
      histological types were excluded. Surgical staging rates were compared according
      to preoperative pathology. Primary outcome measure was the concordance between
      preoperative and final pathology, expressed as a Spearman correlation coefficient
      (rho). A multivariable logistic regression estimated the effects of demographic
      variables and grade on our outcome measure. RESULTS: There were 1804 evaluable
      cases in this study. For preoperative grades 1, 2, and 3 endometrioid
      adenocarcinoma, surgical staging rates were 9.1%, 13.7%, and 25.6%, respectively.
      Concordance rates with final pathology were 73%, 52%, and 53%, respectively.
      There was only moderate concordance between preoperative and final pathology (rho
      = 0.52). There was no significant difference in concordance rates according to
      age, year, or hospital volume, but lower concordance rates among teaching
      hospitals. CONCLUSION: Preoperative biopsy has only a moderate ability to predict
      final pathology in endometrial cancer, and therefore, additional factors should
      be considered in selecting patients for a surgical staging procedure.

PMID- 19407564
TI  - Prognostic factors in early-stage leiomyosarcoma of the uterus.
AB  - Uterine leiomyosarcomas (LMSs) are rare cancers representing less than 1% of all
      uterine malignancies. Clinical International Federation of Gynecology and
      Obstetrics (FIGO) stage is the most important prognostic factor. Other
      significant prognostic factors, especially for early stages, are difficult to
      establish because most of the published studies have included localized and extra
      pelvian sarcomas. The aim of our study was to search for significant prognostic
      factors in clinical stage I and II uterine LMS. The pathologic features of 108
      uterine LMS including 72 stage I and II lesions were reviewed using standardized
      criteria. The prognostic significance of different pathologic features was
      assessed. The median follow-up in the whole group was 64 months (range, 6-223
      months). The 5-year overall survival (OS) and metastasis-free interval and local
      relapse-free interval rates in the whole group and early-stage group (FIGO stages
      I and II) were 40% and 57%, 42% and 50%, 56% and 62%, respectively. Clinical FIGO
      stage was the most important prognostic factor for OS in the whole group (P = 4 x
      10). In the stage I and II group, macroscopic circumscription was the most
      significant factor predicting OS (P = 0.001). In the same group, mitotic score
      and vascular invasion were associated with metastasis-free interval (P = 0.03 and
      P = 0.04, respectively). Uterine LMSs diagnosed using standardized criteria have
      a poor prognosis, and clinical FIGO stage is an ominous prognostic factor. In
      early-stage LMS, pathologic features such as mitotic score, vascular invasion,
      and tumor circumscription significantly impact patient outcome.

PMID- 19407565
TI  - Lymphatic mapping in endometrial cancer: comparison of hysteroscopic and
      subserosal injection and the distribution of sentinel lymph nodes.
AB  - INTRODUCTION: Endometrial cancer incidence increases over the age of 65 and
      lymphadenectomy in these women is a morbid procedure. Sentinel lymph node (SLN)
      should avoid extensive lymphadenectomy in node negative patients. The aim of this
      prospective study is to determine the feasibility and usefulness of lymphatic
      mapping and SLN identification in the management of endometrial cancer. METHODS:
      From January 2004 to December 2007 101 women with endometrial cancer participated
      in the study. We injected Tc hysteroscopically, peritumorally 2 hours before
      laparotomy in 24 women. We applied Tc and blue dye subserously after laparotomy
      and before adhesiolysis in 67 women. Ten patients with metastatic disease in
      ovary, omentum, peritoneum, and bulky nodes were excluded from analysis. RESULTS:
      We detected SLN in 12 women (50%) in hysteroscopic group and in 49 women (73.1%)
      in subserous group. We identified 133 SLNs in 61 women. We found 20 SLNs (15.0%)
      in supraobturator region, 78 (58.6%) in external iliac area, 11 (8.3%) in
      paraaortal area, 13 (9.8%) on common iliac artery, 8 (6.0%) in medial part of
      lateral parametrium, and 3 (2.3%) in presacral area. CONCLUSIONS: Sentinel lymph
      node identification is a new strategy that can be used to examine nodal status
      with a high successful rate in breast, cervical, and vulvar cancer. Results in
      endometrial cancer are not as successful, however. In the future, it will be
      necessary to find optimal timing, the best route of application, and the "right"
      size of the Tc particles. Subserous application seems to be superior to
      hysteroscopic application.

PMID- 19407566
TI  - Practice patterns of radiotherapy in endometrial cancer among member groups of
      the gynecologic cancer intergroup.
AB  - PURPOSE: To describe radiotherapeutic practice of the treatment of endometrial
      cancer in members of the Gynecologic Cancer Intergroup (GCIG). METHODS: A survey
      was developed and distributed to the members of the GCIG. The GCIG is a global
      association of cooperative groups involved in the research and treatment of
      gynecologic neoplasms. RESULTS: Thirty-four surveys were returned from 13
      different cooperative groups. For the treatment of endometrial cancer after
      hysterectomy, mean (SD) pelvic dose was 47.37 (2.32) Gy. The upper border of the
      pelvic field was L4/5 in 14 respondents, L5/S1 in 13 respondents, and not
      specified in 6 surveys. When vaginal brachytherapy (VBT) was used in conjunction
      with external beam radiotherapy, most groups used high dose rate versus low dose
      rate on 24 versus 5 respondents, respectively. Twenty-eight of the 34 respondents
      performed computed tomographic simulation. Intensity-modulated radiotherapy was
      used routinely in 3 of the 34 respondents. For a para-aortic field, the upper
      border was, most commonly, at the T12-L1 interspace (17 of the 28 respondents),
      and the mean (SD) dose was 46.15 (2.18) Gy. For VBT alone after hysterectomy, 23
      groups performed high-dose-rate brachytherapy (27.57 [10.13] Gy in a mean of 4.3
      insertions), and 5 groups used low-dose-rate brachytherapy (41.45 [17.5] Gy).
      Nineteen of the 28 respondents measured the doses to the bladder and the rectum
      when performing VBT. For brachytherapy, there was no uniformity in the fraction
      of the vagina treated or the doses and schedules used. CONCLUSIONS: Radiotherapy
      practices among member groups of the GCIG are similar in doses and dose per
      fraction with external beam. There is a moderate discrepancy in the brachytherapy
      practice after hysterectomy. There are no serious impediments to intergroup
      participation in radiation oncology practices among GCIG members with the use of
      external beam.

PMID- 19407567
TI  - Comparison of laparoscopy and laparotomy for management of endometrial carcinoma:
      a meta-analysis.
AB  - BACKGROUND: This meta-analysis was performed to investigate the outcome of
      laparoscopic surgery for endometrial carcinoma compared with laparotomy. METHODS:
      We searched the MEDLINE (PubMed), EMBASE, and Cochrane Review databases in
      September 2007. Three independent evaluators selected the articles according to
      predetermined selection criteria. RESULTS: Thirteen comparative studies (5
      prospective and 8 retrospective) that met the selection criteria were included.
      In a fixed-effects meta-analysis, the overall survival and therecurrence rate
      showed no significant differences between the laparoscopy and the laparotomy
      groups, with odds ratios of 0.84 (95% confidence interval, 0.64-1.62) and 0.90
      (95% confidence interval, 0.49-1.16), respectively. However, the complication
      rate was lower in the laparoscopy group than in the laparotomy group with an odds
      ratio of 0.43 (95% confidence interval, 0.32-0.58). CONCLUSIONS: The survival
      outcome and recurrence rate after laparoscopic surgery for endometrial carcinoma
      were similar to those in the laparotomy procedures. However, the complication
      rate was lower after laparoscopy compared with laparotomy.

PMID- 19407568
TI  - Conization using electrosurgical conization and cold coagulation for
      international federation of gynecology and obstetrics stage IA1 squamous cell
      carcinomas of the uterine cervix.
AB  - OBJECTIVE: This study was performed to evaluate the efficacy and feasibility of
      electrosurgical conization and cold coagulation as definitive treatments for
      patients with International Federation of Gynecology and Obstetrics stage IA1
      squamous cell carcinoma of the cervix and a resection margin free from
      (micro)invasive carcinoma after conization. METHODS: Patients with stage IA1
      cervical squamous cell carcinoma without lymphovascular space invasion who had
      been treated by electrosurgical conization and cold coagulation and who wanted to
      preserve fertility (or only undertake conservative treatment) were followed up
      without further surgical intervention. Patients with invasive or microinvasive
      carcinoma at resection margins or positive endocervical resection margins were
      excluded from the study. Cervicovaginal smears and colposcopic examination were
      performed at regular intervals. Disease recurrence was defined as a histologic
      diagnosis of cervical intraepithelial neoplasia 2 or higher-grade lesions.
      RESULTS: A total of 85 patients enrolled were deemed eligible to be involved in
      the study. The median follow-up period was 81.0 months (range, 13-127 months).
      Nineteen of the 85 patients had exocervical resection margins. There was one case
      of recurrence, which was node-positive invasive cancer recurrence (1.2%, 1/85),
      in patients with negative resection margins. CONCLUSIONS: These results suggest
      that electrosurgical conization with cold coagulation is a feasible treatment and
      could be used as a definitive therapy for patients with stage IA1 cervical
      squamous cell carcinoma without lymphovascular space invasion. In addition,
      patients having cervical intraepithelial neoplasias 2 and 3 at exocervical
      resection margins could be followed up carefully without further treatment after
      conization and cold coagulation.

PMID- 19407570
TI  - A retrospective study of patients with locally advanced cancer of the cervix
      treated with neoadjuvant chemotherapy followed by radical surgery.
AB  - New concept of downstaging locally advanced cancer of the cervix (LACC) with
      neoadjuvant chemotherapy (NACT), to make it resectable, is of great interest and
      needs to be explored. This is a retrospective study of 56 LACC patients. Efficacy
      of NACT was measured in terms of optimal pathological response (OR). Percentage
      of patients who needed adjuvant radiotherapy and disease-free interval at 2 years
      was evaluated. Clinically, 49 patients (87.5%) responded well to NACT with TIP
      regimen (paclitaxel, ifosfamide, and cisplatin) and underwent radical surgery.
      Adjuvant radiation was given for adverse factors in histopathology. Recurrences
      were noted; 46.4% of patients were in stage 2b, followed by 25% in stage IIIb;
      92.8% of patients had squamous cell carcinoma. Optimal pathological response was
      seen in 15 patients (30.6%) with complete response in 8 patients (16.3%). Four
      patients (8.2%) had deposits in the parametrium, and 11 (22.4%) had positive
      nodes. On gross examination, 48.9% of patients had complete disappearance of
      cervical growth, and there was no microscopic evidence of cervical malignancy in
      16.3%. In 20.4% of patients, cervical cancer was reduced to cervical
      intraepithelial neoplasia or microinvasion. Thirty-four patients (69.4%) needed
      full adjuvant radiotherapy. Overall, 14 patients (25.92%) had recurrence, with 11
      (22.44%) being in NACT and radical surgery group. At 2 years, disease-free
      interval for 49 patients who underwent radical surgery was 69%. This study
      suggests that LACC patients who respond to NACT are surgically resectable with
      pathological cure in some cases, who are then spared from adjuvant radiation,
      which is given when recurrence occurs. However, with advancing stage, the
      percentage of OR decreases, and the need of adjuvant radiation increases.

PMID- 19407569
TI  - Cervical cancer screening among college students in ghana: knowledge and health
      beliefs.
AB  - BACKGROUND: Cervical cancer is the most incident cancer and the leading cause of
      cancer mortality in women in Ghana. Currently, little is known about Ghanaian
      women's knowledge and beliefs about cervical cancer screening, yet this
      information is essential to the success of cervical cancer screening programs.
      Therefore, the purpose of this study was to describe the knowledge and beliefs of
      female university college students in Ghana. METHODS: A cross-sectional survey
      among college women in a university in Ghana elicited information about
      sociodemographics, knowledge and beliefs, and acceptability of cervical cancer
      screening, screening history, and sexual history. Bivariate analyses were
      conducted to identify factors associated with screening. RESULTS: One hundred
      forty women were recruited; the age range was 20 to 35 years. The prior
      Papanicolaou (Pap) screening rate was 12.0%. The women were unaware of local
      screening initiatives, and only 7.9% were aware of the link between human
      papillomavirus and cervical cancer. The most prevalent barriers were lack of
      awareness that the purpose of Pap screening is to diagnose cancer, concerns about
      what others may think, and lack of information about how to obtain screening
      services. Although women perceived the benefits of screening, only about half
      perceived themselves to be at risk. Women received few screening cues. Three
      barriers were negatively associated with screening in bivariate analyses: lack of
      belief that cancer is diagnosed by cervical screening, belief that Pap test is
      painful, and belief that the test will take away virginity. CONCLUSION: New
      screening programs in Ghana should address these barriers and increase screening
      cues to the public.

PMID- 19407571
TI  - Impact of platinum on the whole mitochondrial genome of ovarian carcinomas both
      in vivo and in vitro.
AB  - OBJECTIVES: To investigate somatic mitochondrial DNA mutation in primary and
      recurrent ovarian carcinoma tissues as well as that in drug-resistant cell lines
      to illuminate the impact of chemotherapeutic drugs on mitochondrial DNA (mtDNA).
      METHODS: Complete mtDNA genomes of 20 pairs of ovarian carcinomas and their
      matched normal tissues together with 2 ovarian carcinoma cell lines and their 4
      platinum-resistant cell lines were sequenced. Mitochondrial DNA alterations,
      consequent amino acid alterations were compared between the 2 groups of patients
      and the 2 types of cell lines. RESULTS: A large number of mtDNA new polymorphisms
      (55) and mutations (18) were identified in 20 ovarian carcinoma samples. Platinum
      based chemotherapy did not increase the number of new polymorphisms (P = 0.094),
      mutations (P = 0.688), and consequent amino acid alterations (P = 0.202 and
      0.795). Data gained from the cell lines also indicated that platinum had some
      effect on the mitochondrial genome but not specific to particular positions.
      CONCLUSIONS: What we found suggested that mtDNA damage could be made by
      chemotherapeutic drugs but not as much as imagined in ovarian carcinomas. Some of
      the mtDNA defects might be part of the disease processes and cell properties as
      well as a consequence of treatment.

PMID- 19407572
TI  - Management of surgical stage III and IV endometrioid endometrial carcinoma: an
      overview.
AB  - This paper covers an overview of the literature on the management of advanced
      endometrial cancer, concentrating on patients with histopathologic endometrioid
      type of tumors. The different treatment modalities are described and management
      recommendations are proposed.The standard surgical procedure includes an
      extrafacial total hysterectomy with bilateral salpingo-oophorectomy, collection
      of peritoneal washings for cytology, and exploration of the intraabdominal
      contents. In cases of extensive disease in the abdomen, an optimal surgical
      cytoreduction is associated with improved survival. Further treatment with
      radiotherapy may be indicated based on the pathological staging information to
      improve loco-regional control. Primary radiotherapy is indicated in cases where
      surgery is contraindicated. Systemic treatment can either be hormone therapy or
      chemotherapy. Progesterons are the cornerstone of hormone therapy. Prognostic
      factors for response are the presence of high levels of progesterone and estrogen
      receptors and low grade histology. Paclitaxel is the most active single agent
      drug. The combination therapy with paclitaxel and carboplatin is adopted as first
      choice in patients with endometrial cancer because of the efficacy and low
      toxicity, although not proven in a randomized trial.The literature on the
      management of patients with advanced endometrial cancer is discussed in detail.
      Each stage of advanced disease is presented separately, and management
      recommendations are proposed, and alternative approaches are given.Ongoing
      clinical trials are described, and the focuses of ongoing research are mentioned.

PMID- 19407573
TI  - Attitudes regarding the use of hematopoietic colony-stimulating factors and
      maintenance of relative dose intensity among gynecologic oncologists.
AB  - OBJECTIVE: To assess the attitudes regarding the use of colony-stimulating factor
      (CSF) and the maintenance of relative dose intensity (RDI) by gynecologic
      oncologists during the administration of chemotherapy to patients with epithelial
      ovarian cancer. METHODS: A nationwide survey of 608 gynecologic oncologists was
      performed using a 19-point questionnaire. The questionnaire assessed the
      following domains: (1) demographic information, (2) patterns of CSF use during
      first-line and relapse chemotherapies for patients with epithelial ovarian
      cancer, and (3) use of CSFs to maintain RDI. RESULTS: The response rate to the
      survey was 42% (n = 255). Eighty-six percent (220/255) of the respondents
      routinely administer chemotherapy. In the first-line setting, 67% of physicians
      who routinely administer chemotherapy preferred to use CSFs for secondary
      prophylaxis after a neutropenic complication, whereas only 2% would use CSFs for
      primary prophylaxis. In the recurrent disease setting, physicians were more
      likely to administer a regimen with minimal myelosuppression (74% reported
      "likely" or "very likely"), to dose delay or modify if neutropenic complications
      occur (78%), or to administer CSFs for secondary prophylaxis (85%) than to dose
      attenuate upon initiation of chemotherapy (49%) or to administer CSFs for primary
      prophylaxis (46%). Most physicians would administer CSFs to maintain RDI in both
      the first-line (75%) and palliative settings (62%), and 49% would strive to
      maintain a dose intensity of more than 85%. CONCLUSIONS: Most gynecologic
      oncologists use CSFs as secondary prophylaxis for neutropenic complications
      rather than as primary prophylaxis. Most gynecologic oncologists monitor RDI and
      use CSFs to maintain RDI in their patients with ovarian carcinoma.

PMID- 19407574
TI  - Three-day topotecan schedule in heavily pretreated recurrent ovarian cancer
      patients.
AB  - OBJECTIVE: To evaluate the clinical benefit of a 3-day topotecan schedule in
      heavily pretreated recurrent ovarian cancer patients scheduled for palliative
      treatment. METHODS: Eligibility criteria were 2 or more prior chemotherapy
      regimens, Eastern Cooperative Oncology Group performance status of 2 or less;
      adequate organ function, assessable disease by serum CA-125 measurement before
      each cycle; and 1 or more cycle of topotecan (1.5 mg/m per day) on 3 consecutive
      days of a 28-day treatment cycle. Toxicity was graded according to the National
      Cancer Institute Common Toxicity Criteria version 3. Tumor response, stable
      disease, and progression were evaluated on the basis of CA-125 levels. RESULTS: A
      total of 68 patients were considered eligible for the study. Median age was 58
      years (range, 40-77 years), and the median number of prior chemotherapy regimens
      was 2 (range, 2-6). A total of 272 cycles of topotecan were administered, with a
      median of 4 cycles per patient (range, 1-8). No treatment delays or dose
      reduction was recorded. Major toxicities were grade 3/4 (18%) neutropenia,
      neutropenic fever (6%), grade 4 thrombocytopenia (3%), requirements for blood
      (5%), and platelet transfusions (3%). Thirty-five (54%) of the 64 evaluable
      patients showed a clinical benefit. Of these, 11 patients (17%) had a partial
      response, and 24 (37%) had stable disease with a median time to progression of
      7.5 months (range, 6-10 months) and 4 months (range, 2-6 months), respectively.
      CONCLUSION: More than half of heavily pretreated ovarian cancer patients may
      benefit from 3-day topotecan.

PMID- 19407575
TI  - Incidence of Carboplatin-related hypersensitivity reactions in Japanese patients
      with gynecologic malignancies.
AB  - Carboplatin is one of the most commonly used and well-tolerated agents for
      gynecologic malignancies. The rate of hypersensitivity reactions (HSRs) in the
      overall population of patients receiving carboplatin has been reported to
      increase after multiple doses of the agent. We retrospectively analyzed the
      incidence, clinical features, management, or outcome of carboplatin-related HSRs
      in 113 Japanese patients with gynecologic malignancies and the possibility of
      rechallenge with the drug. We intravenously administered carboplatin after
      paclitaxel or docetaxel. Mild HSRs are resolved by temporary interruption of
      carboplatin infusion, an additional antihistamine, and/or a corticosteroid. If
      HSRs arose, carboplatin was diluted, not exceeding 1 mg/mL, and slowly infused
      over 2 hours in subsequent cycles. Ten patients experienced carboplatin HSRs,
      with an overall incidence of 8.85%. The first HSR episode was mild in all cases.
      When retreated with carboplatin, 4 exhibited severe HSRs. More than 9 cycles
      and/or more than 5000 mg of carboplatin administration significantly increased
      the incidence of HSRs. In particular, carboplatin treatment beyond 15 cycles
      and/or 8000 mg increased the risk of severe HSRs (P < 0.0001). The incidence of
      HSRs in the ovarian carcinoma group was significantly greater than that in the
      uterine carcinoma group (P = 0.0046). Careful attention should be paid to HSRs
      during carboplatin treatment beyond 9 cycles and/or 5000 mg. The rate of severe
      HSRs greatly increases beyond 15 cycles and/or 8000 mg. Further studies are
      needed to identify potential risk factors that may contribute to the development
      of carboplatin HSRs and to decrease the risk of reactions.

PMID- 19407576
TI  - Creation of the miami pouch during laparoscopic-assisted pelvic exenteration: the
      initial experience.
AB  - PURPOSE: To describe the initial experience of laparoscopic hand-assisted Miami
      pouch in a group of patients undergoing pelvic exenterations for pelvic
      malignancies. MATERIALS AND METHODS: Thirteen female patients underwent
      laparoscopic-assisted pelvic exenteration in our center between September 2000
      and November 2007. Six of them had the Miami pouch created for urinary diversion.
      The continent diversion was created extracorporeally through a right iliac fossa
      minilaparotomy. RESULTS: The mean total operative time for the laparoscopic
      assisted exenteration and reconstruction was 382 minutes (range, 270-480
      minutes), but specifically for the Miami pouch, it took a mean time of 106
      minutes (range, 90-130 minutes). Four patients (66.7%) had postoperative urinary
      tract infection that resolved with antibiotics. One patient had a ureteral
      stenosis requiring stenting and one had a Miami pouch cutaneous fistula that
      required a fistulectomy. The mean follow-up was 23 months (range, 9-48 months).
      All patients were continent and were able to self-catheterize approximately 3 to
      6 times/d. CONCLUSIONS: It is technically feasible to incorporate the creation of
      the Miami continent urinary pouch through a minilaparotomy during laparoscopic
      pelvic exenteration without compromising the benefits of laparoscopic surgery.

PMID- 19407578
TI  - What is the standard therapy for bulky stage IB cervical cancer?

PMID- 19407577
TI  - The role of hepatocyte nuclear factor-1beta in the pathogenesis of clear cell
      carcinoma of the ovary.
AB  - PROBLEM: Clear cell carcinoma (CCC) of the ovary has a number of features
      distinguishing it from other epithelial ovarian carcinomas (EOC) because of its
      characteristic histology and biology, frequent concurrence with endometriotic
      lesion, and highly chemoresistant nature resulting in an extremely poor
      prognosis. The incidence of CCC has been steadily increasing in Japan. They
      comprise approximately 20% of all EOC. Understanding the mechanisms of CCC
      development and elucidating pathogenesis and pathophysiology are intrinsic to
      prevention and effective therapies for CCC. METHOD OF STUDY: This article reviews
      the English language literature for biology, pathogenesis, and pathophysiological
      studies on endometriosis-associated EOC. Several data are discussed in the
      context of endometriosis and CCC biology. RESULTS: Recent studies based on genome
      wide expression analysis technology have noted specific expression of hepatocyte
      nuclear factor-1beta (HNF-1beta) in endometriosis and CCC, suggesting that early
      differentiation into the clear cell lineage takes place in the endometriosis. The
      HNF-1beta-dependent pathway of CCC will be discussed, which are providing new
      insights into regulation of apoptosis and glycogen synthesis and resistance of
      CCC to anticancer agents. CONCLUSIONS: This review summarizes recent advances in
      the HNF-1beta and its target genes; the potential challenges to the understanding
      of carcinogenesis, pathogenesis, and pathophysiology of CCC; and a possible novel
      model is proposed.

PMID- 19407579
TI  - Role of diaphragmatic surgery in 69 patients with ovarian carcinoma.

PMID- 19407608
TI  - Tendon transfers: part I. Principles of transfer and transfers for radial nerve
      palsy.
AB  - LEARNING OBJECTIVES: After reading this article (part I of II), the participant
      should be able to: 1. Describe the history of tendon transfer procedures. 2. List
      and understand the principles and biomechanics of tendon transfers. 3. Describe
      the anatomy and function of the radial nerve in the forearm and hand. 4. Describe
      the indications, benefits, and drawbacks for various tendon transfer procedures
      performed for radial nerve palsy. SUMMARY: This article reviews the history of
      tendon transfer procedures, and describes the principles and biomechanics behind
      them. It also discusses the anatomy and clinical findings of radial nerve palsy
      and the tendon transfer procedures used to treat it.

PMID- 19407609
TI  - Rib-sparing internal mammary vessel harvest for microvascular breast
      reconstruction in 100 consecutive cases.
AB  - BACKGROUND: Using the internal mammary vessels as recipient vessels in free-flap
      autologous breast reconstruction has become a common practice. However, these
      vessels are typically accessed by removing a costochondral segment. The purpose
      of this study was to describe the authors' rib-sparing technique for accessing
      the internal mammary vessels that is efficient and reliable and limits chest wall
      morbidity. METHODS: The authors analyzed 100 consecutive free-tissue transfers
      for breast reconstruction in which the internal mammary vessels were accessed
      using a rib-sparing technique. The data were obtained from a prospectively
      maintained database and medical records. RESULTS: Of the 100 free-flap
      reconstructions, 47 used deep inferior epigastric perforator flaps, 45 used
      muscle-sparing transverse rectus abdominis myocutaneous flaps, six used
      superficial inferior epigastric artery flaps, and two used superior gluteal
      artery perforator flaps. No rib cartilage was removed in 66, but a segment of rib
      cartilage was removed in 34 procedures to optimize the exposure and facilitate
      anastomosis. After the initial learning curve, however, the internal mammary
      vessels were used in approximately 90 percent of cases without removal of any rib
      cartilage. The third intercostal space was used to access the internal mammary
      vessels two-thirds of the time, and the second intercostal space was used one
      third of the time. There were no incidences of complications or morbidity
      associated with the rib-sparing approach to internal mammary vessel harvest.
      CONCLUSION: For most patients, the rib-sparing technique is an efficient and safe
      approach for exposing the internal mammary vasculature for microvascular breast
      reconstruction while minimizing chest wall morbidity.

PMID- 19407610
TI  - Financial impact of breast reconstruction on an academic surgical practice.
AB  - BACKGROUND: The financial reimbursement for breast reconstruction is perceived to
      be low. The authors evaluated the financial impact of providing breast
      reconstruction for an academic medical practice and health care system. METHODS:
      The authors examined the billing records for 97 patients undergoing
      postmastectomy breast reconstruction in 2006 at the University of Michigan.
      Professional net revenue was calculated by applying actual collection rates to
      procedural charges. Facility revenue was calculated by applying actual collection
      rates to charges from inpatient care and the operating room. RESULTS: The payer
      mix was 70.1 percent private insurance, 22.7 percent health maintenance
      organization, 3.1 percent Medicare, 2.1 percent Medicaid, and 2.0 percent
      uninsured. The professional revenue and costs allocated to breast reconstruction
      were $242,078 and $177,411, respectively [net profit of $64,667 (27 percent)].
      Health system facility revenue and costs were $1,109,678 and $943,892,
      respectively [net profit of $165,786 (15 percent)]. Physician reimbursement by
      surgical time was highest for delayed tissue expander placement ($1977.70/hour in
      the operating room) and lowest for immediate transverse rectus abdominis
      myocutaneous (TRAM) flaps ($327/hour in the operating room). The facility
      received the greatest average direct margin on TRAM flaps ($3471) and lost money
      on latissimus dorsi flaps (-$398 margin). CONCLUSIONS: Postmastectomy breast
      reconstruction at this academic medical center is fiscally advantageous for both
      the surgical department and the health care system. However, reimbursement varies
      dramatically by type and timing of reconstructive procedure. Although immediate
      postmastectomy reconstructions with TRAM flaps provide superior aesthetic results
      with the greatest amount of patient satisfaction, poor physician reimbursement
      for these labor-intensive procedures may limit the ability of surgeons to provide
      these services because of poor financial return.

PMID- 19407611
TI  - Single-stage breast reconstruction following areola-sparing mastectomy.

PMID- 19407612
TI  - Endothelial cell culture of intramuscular venous malformation and its invasive
      behavior related to matrix metalloproteinase-9.
AB  - BACKGROUND: Intramuscular venous malformation is characterized by abnormal
      morphology of blood vessels. In certain cases, it displays an invasion of
      surrounding tissues. The in vitro model of its endothelial cell culture has not
      been reported, and the pathogenesis of its development is not clear. Matrix
      metalloproteinase-9 is identified to facilitate cell migration and tumor
      progression. The aim of this study was to establish the primary cell culture from
      intramuscular venous malformation and explore its invasive mechanism related to
      matrix metalloproteinase-9. METHODS: Explant culture was adopted to isolate
      endothelial cells from intramuscular venous malformation. In contrast, with human
      umbilical vein endothelial cells collected by collagenase digestion, the
      biological behavior of cell migration and invasion was explored. Western blot,
      reverse-transcription polymerase chain reaction, and immunohistochemical study
      were performed to measure matrix metalloproteinase-9 expression of endothelial
      cells or tissue sections. RESULTS: The primary endothelial cell culture from
      intramuscular venous malformation was established successfully by using explant
      culture. Compared with human umbilical vein endothelial cells, the established
      endothelial cells indicated more powerful capability of migration and invasion
      and expressed more matrix metalloproteinase-9 at both mRNA and protein levels.
      Matrix metalloproteinase-9 mRNA expression in intramuscular venous malformation
      was significantly higher than in normal subcutaneous tissues. The intensity of
      matrix metalloproteinase-9 demonstrated no statistically significant differences
      with varying courses, locations, dimensions, and infiltration degrees.
      CONCLUSIONS: The positive expression of matrix metalloproteinase-9 of
      intramuscular venous malformation tissues and endothelial cells provided
      circumstantial evidence that it may be involved in the pathogenesis of invasive
      biological behavior of the lesions.

PMID- 19407613
TI  - Improved survival of murine island skin flaps by prevention of reperfusion
      injury.
AB  - BACKGROUND: Studies have demonstrated that blocking a single specificity of self
      reactive immunoglobulin M with a 12-amino acid peptide mimic of the antigen of
      immunoglobulin M can attenuate murine intestinal and skeletal muscle injury
      following ischemia and reperfusion. The aim of this study was to ascertain
      whether peptide (P8) had protective effects in an axial island skin flap model,
      where tissue loss is attributed to ischemia-reperfusion injury. METHODS: Dorsal
      lateral thoracic artery island skin flaps (3.5 x 1.5 cm) were elevated in 82 male
      C57BL/6 mice and rendered ischemic for 10 hours by placing a 7-mm microclamp on
      the vascular pedicle followed by 7 days of reperfusion. Group I (n = 7), the sham
      group, had no clamp placed. Group II (n = 21) had clamp placement but no other
      treatment. Thirty minutes before clamp placement, group III (n = 18) received
      0.25 cc of saline intravenously, group IV (n = 18) received 25 microg/0.25 cc P8
      peptide, and group V (n = 7) received 25 microg/0.25 cc random 12-mer peptide.
      Animals in group VI (n = 11) underwent two cycles of 20 minutes of ischemic
      preconditioning before 10 hours of ischemia. After 1 week of reperfusion, percent
      necrosis was measured and results were compared using analysis of variance and an
      unpaired t test. RESULTS: In animals treated with P8 peptide, flap necrosis was
      14.61 +/- 2.77 percent. This represents a statistically significant, 56 percent
      reduction in flap necrosis compared with controls (p < 0.001). CONCLUSION: These
      data demonstrate that prevention of ischemia-reperfusion injury with P8 peptide
      produces a significant reduction in necrosis of treated flaps.

PMID- 19407614
TI  - The connexin43 carboxyl-terminal peptide ACT1 modulates the biological response
      to silicone implants.
AB  - BACKGROUND: The implantation of a biomedical device elicits a wound-healing
      response that progresses through the three phases of wound healing: inflammation,
      cellular proliferation, and matrix remodeling. This response culminates in a
      fibrous collagen encapsulation of the implant. Subsequent contraction of this
      "scar-like" tissue can lead to physical disfigurement, implant extrusion, or
      impairment of implant function, necessitating surgical revision or removal. ACT1
      is a synthetic peptide derived from the carboxyl-terminal sequence of the
      cellular gap junction protein connexin43. This novel peptide has recently been
      shown to modulate cutaneous wound healing, reduce scarring, and promote
      regenerative repair of the skin following injury. In this study, the authors
      investigated the ability of the ACT1 peptide to modulate the wound-healing
      response to biomedical device implantation. METHODS: Silicone disks coated with
      either vehicle control or ACT1 peptide were implanted submuscularly into male
      Sprague-Dawley rats. Capsulectomies were performed on days 1, 2, 3, 14, and 28.
      The implant capsules and surrounding tissue were analyzed histologically and
      biochemically. RESULTS: ACT1 modulated the wound-healing response to silicone
      implants by attenuating neutrophil infiltration, increasing vascularity of the
      capsule tissue, reducing type I collagen deposition around the implant, and
      reducing the continued presence of contractile myofibroblasts. CONCLUSION: ACT1
      may provide an enabling technology for modulating the wound-healing response to
      implants, promoting integration of implanted materials and tissue-engineered
      devices in the human body.

PMID- 19407615
TI  - Indications and outcomes for surgical treatment of patients with chronic migraine
      headaches caused by occipital neuralgia.
AB  - BACKGROUND: Occipital neuralgia is a headache syndrome characterized by
      paroxysmal headaches localizing to the posterior scalp. The critical diagnostic
      feature is symptomatic response to local anesthetic blockade of the greater or
      lesser occipital nerve. Further characterization is debated in the literature
      regarding the diagnosis and optimal management of this condition. The authors
      present the largest reported series of surgical neurolysis of the greater
      occipital nerve in the management of occipital neuralgia. METHODS: A
      retrospective chart review was conducted to identify 206 consecutive patients
      undergoing neurolysis of the greater or, less commonly, excision of the greater
      and/or lesser occipital nerves. A detailed description of the procedure is
      presented, as is the algorithm for patient selection and timing of surgery.
      Preoperative and postoperative visual analogue pain scores and migraine headache
      indices were measured. Success was defined as a reduction in pain of 50 percent
      or greater. RESULTS: Of 206 patients, 190 underwent greater occipital nerve
      neurolysis (171 bilateral). Twelve patients underwent greater and lesser
      occipital nerve excision, whereas four underwent lesser occipital nerve excision
      alone. The authors found that 80.5 percent of patients experienced at least 50
      percent pain relief and 43.4 percent of patients experienced complete relief of
      headache. Mean preoperative pain score was 7.9 +/- 1.4. Mean postoperative pain
      was 1.9 +/- 1.8. Minimum duration of follow-up was 12 months. There were two
      minor complications. CONCLUSION: Neurolysis of the greater occipital nerve
      appears to provide safe, durable pain relief in the majority of selected patients
      with chronic headaches caused by occipital neuralgia.

PMID- 19407616
TI  - Clinical application and outcome of the segmental pectoralis major free flap in
      five head and neck patients.
AB  - BACKGROUND: Although microsurgical transplantation of the sternocostal segment of
      the pectoralis major muscle shares most of the advantages of the latissimus dorsi
      free flap, the latter has become a workhorse of microsurgery and the segmental
      pectoralis major free flap has not. By presenting their clinical experience with
      primary transplantations of this free flap to reconstruct craniofacial defects,
      the authors intend to draw more attention to its application and promote its use
      in reconstructive surgery. METHODS: Segmental pectoralis major free flaps were
      used for reconstruction of craniofacial defects in four male oncologic patients
      and one female trauma patient with a mean age of 55 years (range, 37 to 68
      years). The donor-site morbidity was limited by preserving the clavicular muscle
      segment and its innervation. In one patient, only part of the sternocostal
      segment of the muscle was harvested, whereas in another, the free flap's vascular
      pedicle was anastomosed to the vascular pedicle of the contralateral pedicled
      pectoralis major flap. RESULTS: Total flap loss occurred in the one trauma
      patient and repeated surgery for wound-healing problems was required in one of
      the oncologic patients. Still, final flap outcome was favorable in four of the
      five patients. CONCLUSIONS: The segmental pectoralis major free flap is a useful
      and justifiable adjunct to the microsurgical techniques available for flat or
      wide craniofacial defects. It has the advantage over the latissimus dorsi flap of
      allowing a simultaneous two-team approach with the patient in supine position.

PMID- 19407617
TI  - New technique for marking the location of Mustarde horizontal mattress sutures.

PMID- 19407618
TI  - Anatomical and clinical studies of the supraclavicular flap: analysis of 103
      flaps used to reconstruct neck scar contractures.
AB  - BACKGROUND: The supraclavicular flap is an excellent flap that has been used
      widely, but its vascular reliability remains unclear. In this article, the
      authors report the results of their anatomical studies on 40 flaps from 20
      preserved cadavers and their clinical studies of 103 supraclavicular flaps in 101
      patients. METHODS: In their anatomical study, the authors analyzed the important
      anatomical features that are useful for harvesting flaps. In their clinical
      study, the authors analyzed the cases in terms of flap reliability. RESULTS: The
      supraclavicular artery branched from the transverse cervical artery in all 40
      specimens (100 percent). Although it arose from the middle third of the clavicle
      in 90 percent of the specimens, it arose from the lateral third of the clavicle
      in four specimens (10 percent). Moreover, the transverse cervical artery
      originated from the subclavian artery in two of 40 specimens (5 percent) rather
      than from the thyrocervical trunk. The origins of the supraclavicular and
      transverse cervical arteries were on average 4.12 cm apart (range, 3 to 5.5 cm).
      In our clinical study, 101 of the 103 flaps (98.1 percent) were (vascular
      pedicled) island flaps and five (4.9 percent) were transferred under a skin
      tunnel. We also performed a supercharged flap transfer using posterior circumflex
      humeral vessels. Of the 103 flaps, 97 survived completely (94.2 percent), but
      four and two exhibited superficial distal necrosis (3.9 percent) and total
      necrosis (1.9 percent), respectively. CONCLUSIONS: Supraclavicular flaps are
      reliable, but vascular anomalies exist. In the authors' experience, the posterior
      circumflex humeral artery could be used for supercharging the supraclavicular
      flap.

PMID- 19407619
TI  - The Patient Scar Assessment Questionnaire: a reliable and valid patient-reported
      outcomes measure for linear scars.
AB  - BACKGROUND: There is a lack of rigorously validated patient-based outcomes
      measures of scarring. The aim of this study was to construct such a scale and
      demonstrate reliability and validity by applying the scale in a wide range of
      scarring samples. METHODS: The Patient Scar Assessment Questionnaire with five
      subscales (i.e., Appearance, Symptoms, Consciousness, Satisfaction with
      Appearance, and Satisfaction with Symptoms) was constructed using multiple
      categorical response items. The Patient Scar Assessment Questionnaire was applied
      to various surgical samples (total scar assessments n = 667) at months 3, 6, and
      12 after surgery (and preoperatively in the scar revision group) and tested for
      internal consistency, test-retest reliability, convergent validity, known group
      differences, and sensitivity, against widely accepted criteria from psychometric
      measurement science. RESULTS: Subscales showed high internal consistency
      (Cronbach alpha, 0.73 to 0.93), except the Symptoms subscale. Test-retest
      reliability was high across all subscales (intraclass correlation coefficient,
      0.74 to 0.87) across all groups except the scar revision group. Change in Patient
      Scar Assessment Questionnaire scores was significant between months 3 and 6
      postoperatively (p < 0.001) and subscales demonstrated known group differences (p
      < 0.001). Convergent validity was demonstrated by significant moderate
      correlations with various measures of similar constructs (r = 0.26 to 0.61, p <
      0.001). CONCLUSIONS: The Patient Scar Assessment Questionnaire is a reliable and
      valid measure of the patient's perception of scarring, although the Symptoms
      subscale requires further refinement. Subscales can be used independently of each
      other to allow assessment of scar change in specific domains.

PMID- 19407620
TI  - Immediate versus delayed one-stage sternal debridement and pectoralis muscle flap
      reconstruction of deep sternal wound infections.
AB  - BACKGROUND: The management of postoperative deep sternal wound infection varies
      widely based on the discretion of the cardiovascular surgeon and the plastic
      surgeon. METHODS: Analysis of patients with deep sternal wound infection
      undergoing one-step radical sternal debridement and muscle flap reconstruction by
      a single plastic surgeon from 1986 to 2008 was conducted. Two groups of patients
      were identified. The immediate group was referred soon after diagnosis of sternal
      wound infection and without any debridement. The delayed group was referred much
      later after undergoing an extended management by their cardiovascular surgeon.
      Retrospective review was performed to compare morbidity, mortality, and length of
      stay between the two groups. RESULTS: There were a total of 583 patients with
      deep sternal wound infection. Of the 497 patients referred immediately, 22 (4.4
      percent) patients required mechanical ventilation for an average of 4 days, eight
      (1.6 percent) required tracheotomy, 13 (2.6 percent) developed stage III/IV
      pressure sores, 24 (4.8 percent) developed major wound dehiscence, zero (0
      percent) required skin grafting, average length of stay was 4.7 days, and five
      died (1 percent). Of the 86 patients with a delayed referral, 40 (46.5 percent)
      required mechanical ventilation for an average of 18.3 days, 31 (36 percent)
      required tracheotomy, 20 (23.3 percent) developed stage III/IV pressure sores, 12
      (14 percent) developed major wound dehiscence, nine (10.5 percent) required skin
      grafts, the average length of stay was 19.3 days, and four died (4.7 percent).
      CONCLUSION: Patients with deep sternal wound infection following sternotomy
      benefit from one-step radical sternal debridement and muscle flap(s)
      reconstruction, as it results in a significant decrease in morbidity, mortality,
      and length of stay.

PMID- 19407621
TI  - Surgical management of the symptomatic unstable sternum with pectoralis major
      muscle flaps.
AB  - BACKGROUND: Sternal nonunion after median sternotomy is an uncommon but
      potentially disabling complication. The management of nonunion varies based on
      the discretion of the cardiovascular surgeon. METHODS: An analysis of all
      patients with symptomatic sternal nonunion who underwent wire removal, subtotal
      sternal debridement, and muscle flap reconstruction from 1993 to 2008 was
      conducted. A retrospective review was performed to evaluate preoperative and
      postoperative symptoms, pain scores, procedures, length of hospital stay,
      operating time, complications, morbidity, and mortality. RESULTS: A total of 24
      patients were identified. The male-to-female ratio was 11:1. Time from initial
      median sternotomy to consultation ranged from 5 to 48 months. All were referred
      when stability was not achieved by other means. None of the patients had clinical
      or laboratory evidence of sternal wound infection at presentation. The patients
      rated their preoperative pain severity at an average of 7.7 and a maximum of 10
      on a scale of 1 to 10. All intraoperative cultures showed no growth. The
      operating time averaged 104 minutes. The average length of stay for these
      patients was 2.5 days. Follow-up ranged from 2 to 15 months, with an average of
      4.2 months. All patients had clinically improved sternal stability. CONCLUSIONS:
      All patients experienced improvement of their preoperative symptoms, particularly
      pain, popping, and grinding. Average pain severity dropped from 7.7
      preoperatively to 2.2, with a maximum of 4. Two patients developed seroma and
      required operative drainage. Both went on to complete healing. The mortality rate
      was 0 percent.

PMID- 19407622
TI  - Risk analysis for the reverse sural fasciocutaneous flap in distal leg
      reconstruction.
AB  - BACKGROUND: The reverse sural fasciocutaneous flap provides the potential for
      simple and efficient closure of distal leg, ankle, and foot defects. In young
      patients with traumatic injuries, low complication rates have been reported. The
      authors hypothesize that extending its use to older patients with comorbidities
      results in a higher complication rate. METHODS: The authors retrospectively
      reviewed 58 consecutive reverse sural fasciocutaneous flap in 57 patients for
      distal leg reconstruction. Outcomes were compared between patients with no
      comorbidities (n = 31) and those with a history of smoking, diabetes mellitus, or
      peripheral arterial disease (n = 26). Standard statistical analyses were
      performed, including logistic regression. RESULTS: Patients had a mean age of 53
      years and a median follow-up of 20 months. Fifty percent of flaps had
      postoperative complications, with nine (16 percent) major complications (three
      total flap losses and six partial losses), 17 (29 percent) minor complications,
      and three infections. In patients without comorbidities, there were no major
      complications and five minor complications (16 percent). Significantly higher
      major and minor complication rates were seen in older patients and patients with
      a history of smoking, obesity, diabetes, or peripheral arterial disease.
      Multivariate regression analysis identified smoking as the risk factor most
      independently associated with any reverse sural fasciocutaneous flap
      complication. Importantly, surgical delay procedures were associated with
      decreased ischemic flap complications in patients with comorbidities.
      CONCLUSIONS: Although the reverse sural fasciocutaneous flap is reliable in young
      healthy patients, it has significant complication rates in patients with
      comorbidities, especially smokers. In such patients, the reverse sural
      fasciocutaneous flap requires multiple operative revisions and a surgical delay
      should be considered.

PMID- 19407623
TI  - The unfavorable anatomy of vastus lateralis motor nerves: a cause of donor-site
      morbidity after anterolateral thigh flap harvest.
AB  - BACKGROUND: The anterolateral thigh flap is a popular reconstructive option, with
      a major advantage being its low donor-site morbidity. However, donor-site
      morbidity following anterolateral thigh flap harvest does occur, with postulated
      causes including damage to muscle, deep fascia, and the motor nerves to the
      vastus lateralis. No anatomical studies have yet described the relationship of
      these motor nerves to the vascular pedicle of the anterolateral thigh flap.
      METHODS: Thirty-six human cadaveric thighs underwent dissection studies, and the
      innervation of the vastus lateralis and the relationship of the nerves to the
      descending branch of the lateral circumflex femoral artery were documented.
      Variations were recorded. RESULTS: The nerve to the vastus lateralis branches
      extensively before entering the muscle, with four to seven nerves identified per
      thigh. Two particular variations of the nerve anatomy are uniquely susceptible to
      damage: where the motor nerve passes through the vascular pedicle itself or
      passes between perforators supplying the flap. At least one unfavorable variation
      was present in 28 percent of cases. CONCLUSIONS: The nerves innervating the
      vastus lateralis are intimately related to the vascular pedicle of the
      anterolateral thigh flap. These nerves may be damaged during flap harvest and may
      contribute to donor-site morbidity after anterolateral thigh flap surgery.

PMID- 19407624
TI  - An algorithmic approach to the use of gauze-based negative-pressure wound therapy
      as a bridge to closure in pediatric extremity trauma.
AB  - BACKGROUND: The efficacy of negative-pressure wound therapy as a bridge to
      definitive closure of traumatic extremity wounds has been demonstrated in adults.
      Gauze-based negative-pressure wound therapy has been used to facilitate
      granulation tissue formation and promote closure in a number of wound types. In
      this study, the authors evaluated the efficacy of gauze-based negative-pressure
      wound therapy using the Chariker-Jeter technique for pediatric extremity wounds
      requiring delayed closure. METHODS: A retrospective review was conducted of 24
      pediatric patients presenting with extremity injuries involving soft-tissue
      defects not amenable to immediate primary closure. After initial irrigation,
      debridement, and antibiotic therapy, negative-pressure wound therapy using the
      Chariker-Jeter technique was applied and dressings were changed at 48- to 72-hour
      intervals before secondary closure or primary closure by skin graft, local flaps,
      or free tissue transfer. RESULTS: Granulation tissue was noted in all wounds by
      day 4. The duration of vacuum therapy averaged 10 days in patients whose wounds
      were closed primarily (n = 19) and 17 days in patients who were allowed to heal
      by secondary intention (n = 5). Nine patients' wounds were closed with skin
      grafts and local flaps, eight were closed with local flaps only, and three were
      closed with free tissue transfer. There was no incidence of skin graft loss or
      flap failure. Follow-up evaluation of the wounds averaged 24 months, during which
      no complications were noted. CONCLUSIONS: As a relatively atraumatic wound care
      technique with few complications, gauze-based negative-pressure wound therapy
      with the Chariker-Jeter technique provides a highly effective option for
      temporary soft-tissue management of extremity trauma in pediatric patients.

PMID- 19407626
TI  - Shape-modified radial artery perforator flap method: analysis of 112 cases.
AB  - BACKGROUND: To overcome the donor-site morbidity associated with radial forearm
      flaps, many modifications of this technique have been reported, including the
      development of the perforator flap method. In this article, the authors analyze
      the efficacy of their shape-modified radial artery perforator flap method.
      METHODS: The authors analyzed all of their 112 cases of reconstruction with the
      shape-modified method with regard to the cause of injury, recipient site, whether
      the flap was free or pedicled, flap size, number of components that were divided
      by perforators, flap survival, and quality of the outcome. Donor-site morbidity,
      including the development of scars and dorsal hand numbness, was also evaluated.
      RESULTS: The reconstructed areas were the head and neck (27 cases, 24.1 percent),
      upper extremity (58 cases, 51.8 percent), and lower extremity (27 cases, 24.1
      percent). Free flaps were used in 75 cases (67.0 percent). In total, 109 flaps
      (97.3 percent) survived completely, but three free flaps exhibited venous
      thrombosis. In terms of aesthetics, 48 cases had excellent outcomes (42.9
      percent), 61 cases had good outcomes (54.5 percent), and three cases had poor
      outcomes (2.7 percent). Impaired blood circulation and numbness of the donor hand
      were never observed, but one patient complained about a donor-site cosmetic
      problem. CONCLUSIONS: The authors' flap can be considered as a kind of propeller
      flap. It also resembles the flap-in-flap method. It is suitable for a wide range
      of surgical indications and is useful and safe in not only adults but also young
      and elderly patients.

PMID- 19407625
TI  - Outcomes of pyrolytic carbon arthroplasty for the proximal interphalangeal joint.
AB  - BACKGROUND: Arthritis of the proximal interphalangeal joint is a debilitating
      condition commonly treated with arthroplasty. The pyrolytic carbon (pyrocarbon)
      implant has been developed for proximal interphalangeal joint arthroplasty in
      these patients. This prospective outcomes study evaluated the outcomes and
      complications of the pyrocarbon implant for the proximal interphalangeal joint.
      METHODS: Consecutive candidates for proximal interphalangeal joint arthroplasty
      with pyrocarbon implants were evaluated prospectively. Functional measurements
      and the Michigan Hand Outcomes Questionnaire were administered preoperatively and
      at 3, 6, and 12 months postoperatively. Preoperative means and 12-month
      postoperative means for all functional measures were compared using paired t
      tests and nonparametric Wilcoxon signed rank sum test, and effect size was
      reported for the Michigan Hand Outcomes Questionnaire. RESULTS: Fourteen patients
      treated with 21 implants were enrolled in the study. At the 12-month follow-up
      period, mean active arc of motion was 38 degrees, decreasing slightly from the
      preoperative value. Mean grip strength improved from 11.3 kg to 15.1 kg, although
      the difference was not statistically significant. Mean key pinch values improved
      significantly from 6.6 kg preoperatively to 9.2 kg at the 12-month follow-up (p =
      0.03). Jebsen-Taylor test scores showed improvement, although not significantly.
      Changes in all Michigan Hand Outcomes Questionnaire domains showed a large effect
      size. Three patients experienced squeaking of the implant and three patients
      experienced dislocation of the pyrocarbon joint. CONCLUSION: The pyrocarbon
      implant for proximal interphalangeal joint arthroplasty shows encouraging
      results, primarily in patient satisfaction and pain relief, but is associated
      with complications related to implant dislocations, which required prolonged
      treatment with external fixators.

PMID- 19407627
TI  - Reconstruction of postburn antebrachial contractures using pedicled thoracodorsal
      artery perforator flaps.
AB  - BACKGROUND: Full-thickness burns involving the antecubital area result in severe
      contractures. Functional impairment is inevitable if the affected areas are not
      managed properly. Proper treatment requires complete release and radical excision
      of the scar tissue, followed by reconstruction using durable tissue that will not
      contract during long-term follow-up. METHODS: Nine patients with flexion
      contractures were reconstructed with pedicled thoracodorsal artery perforator
      flaps between 2004 and 2008. All of the patients were male, and their ages ranged
      from 20 to 23 years (mean, 21.4 years). The size and orientation of the skin
      islands were planned according to the defect size and orientation. The size of
      the flaps varied from 6.5 to 9.0 cm in width (mean, 8.0 cm) and 16.0 to 21.0 cm
      in length (mean, 20.0 cm). All of the patients were followed up for 6 to 12
      months (mean, 9.3 months). RESULTS: All of the flaps used on the postburn
      antecubital contractures survived completely. Minimal transient venous congestion
      occurred in two flaps during the early postoperative period. A complete range of
      motion at the elbow joint was achieved in all patients by the end of the
      reconstruction period. CONCLUSIONS: This study revealed that the pedicled
      thoracodorsal artery perforator flap is a suitable alternative for postburn elbow
      contractures. A very long pedicle can be obtained to transfer the flap to the
      antecubital area without tension. With its thin, pliable texture and large size,
      it adapts well to forearm skin and the donor-site scar is considered cosmetically
      acceptable.

PMID- 19407628
TI  - Discharge practices, readmission, and serious medical complications following
      primary cleft lip repair in 23 U.S. children's hospitals.
AB  - BACKGROUND: Discharge timing following primary cleft lip repair balances the
      desire to return patients to their home environment with the risk of serious
      complications occurring outside a hospital. To derive information to help
      estimate these risks, the authors evaluated discharge practices, readmissions,
      and serious medical complications following primary cleft lip repair at 23
      children's hospitals in the Pediatric Health Information System over a 5-year
      period. METHODS: The primary outcomes were discharge the same day as surgery,
      readmission within 48 hours, and a serious medical complication occurring during
      the postoperative admission. Linear mixed models were fit to assess the
      independent association of the covariates with each outcome variable while
      accounting for the correlated nature of the data within each hospital. RESULTS:
      Among 2558 patients undergoing primary cleft lip repair, 27.9 percent underwent
      same-day discharge, and 1.9 percent had an unscheduled readmission; 1.4 percent
      of the admitted patients had serious medical complications within 48 hours of
      their operation. Same-day discharge was associated with older age of the patient,
      absence of comorbidity, not having Medicaid, and having the surgery in a hospital
      with a higher annual volume of primary cleft lip repairs. Readmission was
      associated with Medicaid insurance and having had a surgeon with a higher primary
      cleft lip repair volume. Serious medical inpatient complications were associated
      with a preexisting patient comorbidity and a lower surgeon cleft volume.
      CONCLUSIONS: A number of factors related to the hospital, surgeon, patient, and
      patient's family bear consideration in deciding the timing of discharge after
      primary cleft lip repair. The most clinically important factor appears to be the
      overall preexisting medical status of the patient.

PMID- 19407629
TI  - Pfeiffer syndrome: a treatment evaluation.
AB  - BACKGROUND: Pfeiffer syndrome is rarely encountered, even at major craniofacial
      centers. Published reports indicate high mortality rates (25 to 85 percent) for
      severely affected subtypes. The authors reviewed their surgically treated
      patients to improve outcomes. METHODS: The authors conducted a 17-year, single
      center, retrospective outcome assessment of all children treated for Pfeiffer
      syndrome, with data summarized using descriptive statistics. RESULTS: Of 802
      patients treated for craniosynostosis, 28 were identified with Pfeiffer syndrome:
      17 were classified as type I (61 percent), seven were classified as type II (25
      percent), and four were classified as type III (14 percent). The mean age was 10
      years (range, 12 months to 39 years), with an average of 9.3 operations per child
      (2.5 cranial vaults, 1.1 Le Fort III procedures). Fifty-nine percent had external
      auditory canal atresia (100 percent of type III patients), and 29 percent had
      some visual disturbance. Tracheostomies were recommended in 100 percent of type
      II and III patients, and two type II patients required tracheal stenosis repairs.
      Eighty-four percent had acquired Chiari malformations (100 percent of type II and
      III patients), and 61 percent required treatment for hydrocephalus. Fifty percent
      of shunted patients (mean age, 7 years) have required Chiari decompressions, but
      no patients undergoing endoscopic third ventriculostomies (mean age, <3 years)
      have required treatment. The mortality rate was 7 percent, with both deaths
      occurring at home without proximity to surgery. CONCLUSIONS: The authors'
      mortality rates for type II and III Pfeiffer syndrome are lower than those
      previously published. The authors believe a preemptory tarsorrhaphy strategy can
      prevent visual loss and that further reductions in mortality rates are possible
      with aggressive airway management (early tracheostomies) and more frequent
      screening (e.g., magnetic resonance imaging, sleep studies) for Chiari
      malformations.

PMID- 19407631
TI  - Techniques in frontal sinus fracture repair.
AB  - Constituting only 5 percent of facial fractures, frontal sinus fractures are
      relatively uncommon. However, given the great amount of force required to produce
      them, substantial morbidity is often seen. A thorough understanding of corrective
      techniques is essential when approaching these challenging injuries. In cases
      requiring sinus obliteration, it is critical that all mucosa be fully destroyed,
      the nasofrontal meatus completely sealed, and any posterior wall disruptions
      appropriately addressed. In this article, as a supplement to their video
      presentation, the authors discuss the surgical approach to frontal sinus
      fracture.

PMID- 19407630
TI  - Ocular advancement in monobloc distraction.
AB  - BACKGROUND: Monobloc distraction has been demonstrated to be an efficacious,
      safe, and stable method of providing functional and aesthetic improvement in
      children with syndromic craniosynostosis. Although the movement of bony
      structures following monobloc distraction has been quantitatively assessed
      before, objective analysis of the movement of soft tissues, such as the globe,
      has not been published previously. The authors present a method that assesses
      globe movement following monobloc distraction, using computed tomographic scan
      data. METHODS: The preoperative and postoperative computed tomographic scans of
      10 patients with Pfeiffer's and Crouzon's syndromes, undergoing monobloc
      distraction, were assessed. Scan data were loaded into voxel image-rendering
      software that produced a three-dimensional reconstruction. Direct measurements
      between preoperative and postoperative images were taken. RESULTS: An average
      upper face osseous distraction distance of 12.94 mm, with an average lower face
      distraction of 14.19 mm, was achieved in all 10 children. The authors measured
      average globe movements on three planes and calculated an average left eye
      forward movement of 5.28 mm and average right eye forward movement of 6.33 mm. In
      all, globe advancement was approximately two fifths of the distance advanced by
      the surrounding bone. CONCLUSIONS: Forward movement of the globe following
      monobloc distraction has not previously been described. Although there is no
      current evidence for optic nerve stretch and compromise in monobloc surgery, the
      functional implications of these findings should be formally assessed.

PMID- 19407632
TI  - The arterial and venous anatomies of the lateral face lift flap and the SMAS.
AB  - BACKGROUND: Studies of the vascularity of the superficial musculoaponeurotic
      system (SMAS) have suggested that it is an avascular layer. Clinical studies,
      however, suggest that the incidence of skin slough is higher in subcutaneous face
      lift dissections. A reappraisal of the arterial and venous supply of the face
      lift flap using sequential dye injection studies and three-dimensional computed
      tomographic imaging techniques may help to further elucidate the mechanisms
      behind vascular complications following rhytidectomy. METHODS: Studies were
      performed on 24 hemifaces from fresh cadavers. In six heads, injection with a
      barium sulfate/gelatin mixture was performed followed by three-dimensional
      computed tomographic angiography and venography. Four heads underwent arterial
      and venous injection with colored latex followed by dissection studies.
      Sequential dye injection studies were performed in two heads following isolation
      and cannulation of the transverse facial artery and elevation of a composite (sub
      SMAS) rhytidectomy flap followed by subcutaneous dissection. Dye injection
      studies were also performed through the external carotid artery before and after
      ligation of the transverse facial artery. RESULTS: The most significant arterial
      contribution to the lateral face lift flap was from the transverse facial artery
      perforator. Arteries contributed branches to the SMAS on their way to the dense
      subdermal plexus, forming a continuous anastomotic network. The SMAS was devoid
      of veins, but the superficial venous system was found arranged in a polygonal
      configuration at the level of the subdermal plexus. Sequential dye injection
      studies following dissection in a composite then subcutaneous plane with
      preservation of the transverse facial artery perforator revealed reduced
      perfusion of the preauricular skin following dissection in the subcutaneous
      plane. CONCLUSIONS: The composite face lift flap revealed better perfusion in the
      preauricular region compared with a subcutaneous dissection, although much of
      this area is routinely excised during rhytidectomy. The lateral face lift flap is
      perfused predominantly by the transverse facial artery perforator, and its
      ligation results in reduction of perfusion in the preauricular region. These
      findings may have relevance in patients with vascular compromise.

PMID- 19407633
TI  - Surface area measurement of the female breast: phase I. Validation of a novel
      optical technique.
AB  - BACKGROUND: Breast shape is largely determined by the volume of tissue and
      surface area of the skin envelope. Values for breast surface area have never been
      published in the literature. The investigators have developed an inexpensive,
      noninvasive optical method to objectively measure breast volume and surface area,
      and its accuracy is determined. METHODS: An optical grid is projected onto the
      breast, and two images are captured to create a computerized three-dimensional
      model from which volume, surface area, and maximum vertical projection are
      calculated. RESULTS: To assess accuracy, simple geometric shapes (n = 22) were
      analyzed, and the actual volume, surface area, and maximum vertical projection
      were compared with the imaged values using least-squares linear regression. There
      was excellent correlation in all three parameters (r > 0.995, p < 10). The mean
      differences in volume, surface area, and maximum vertical projection were 28 +/-
      28 ml (mean +/- SD), 2 +/- 9 cm, and 0.4 +/- 0.5 cm, respectively. Female breasts
      (n = 14) were then analyzed, and the actual volume and surface area were measured
      using plaster casts. Based on least-squares linear regression, there was
      excellent correlation between the imaged values and actual values (r > 0.992, p <
      10), and the mean differences in volume and surface area were 32 +/- 22 ml and 3
      +/- 11 cm, respectively. CONCLUSIONS: For the first time, an optical method has
      been demonstrated to measure volume and surface area with accuracy. When the
      method is applied to the breast, measurement errors are small and clinically
      insignificant. The ability to facilitate quantitative breast surgery will be
      investigated in future phases of this experiment.

PMID- 19407634
TI  - Abdominoplasty with direct resection of deep fat.
AB  - BACKGROUND: Suction-assisted lipectomy is an integral component of abdominoplasty
      for many surgeons. Its potential to affect the vascularity of the abdominal flap
      is usually offset by limiting the extent of undermining and not suctioning the
      central flap. The authors address whether these guidelines apply to direct
      excision of subscarpal fat and whether direct excision provides aesthetically
      superior abdominoplasty results with fewer complications. METHODS: A 10-year
      review of consecutive abdominoplasty patients (n = 181) was conducted.
      Undermining was done to the xyphoid and just beyond the lower rib margins
      superiorly and at least as far as the anterior axillary line laterally. Fat deep
      to Scarpa's fascia was removed by tangential excision in all zones of the
      abdominal flap, including those considered at high risk for vascular compromise
      if subjected to liposuction after similar undermining. Concurrent liposuction of
      the abdominal flap was not done. Thirty patients had concurrent flank
      liposuction. RESULTS: No patients experienced major full-thickness tissue loss.
      The incidence of limited necrosis at the incision line requiring subsequent scar
      revision was 0.7 percent in the 151 patients having abdominoplasty and 6.7
      percent in the 30 patients having abdominoplasty combined with flank liposuction.
      Erythema and/or epidermolysis was seen in 4.8 percent of the abdominoplasty
      patients and 10 percent of the abdominoplasty/ flank liposuction group. The rate
      of seroma formation in both groups was approximately 16.5 percent. CONCLUSIONS:
      Direct excision of subscarpal fat does not subject any zone of the abdominoplasty
      flap to increased risks of vascular compromise. It is a safe technique that
      provides excellent abdominoplasty results.

PMID- 19407635
TI  - Integrated plastic surgery residency applicant survey: characteristics of
      successful applicants and feedback about the interview process.
AB  - BACKGROUND: Integrated plastic surgery residency training is growing in
      popularity, bringing new challenges to program directors and applicants. The
      purpose of this study was to identify characteristics of successful applicants
      and to obtain feedback from applicants to improve the integrated plastic surgery
      residency training application and interview process. METHODS: An anonymous
      survey assessing applicant academic qualifications, number of interviews offered
      and attended, and opinions about the application and interview process was
      distributed electronically to the 2006 integrated plastic surgery residency
      training applicant class. The number of interviews offered was used as an
      indicator of potential applicant success. RESULTS: A 38 percent survey
      participation rate (139 of 367) was achieved. United States Medical Licensing
      Examination Step 1 score correlated with number of interview invitations (p < or
      = 0.001). Successful Alpha Omega Alpha designation (p < or = 0.001), high class
      rank (p = 0.034), presence of a plastic surgery residency program at the
      participant's school (p = 0.026), and authorship of one or more publications (p <
      or = 0.001) were associated with receiving greater number of interview
      invitations. Geographic location was an important consideration for applicants
      when applying to and ranking programs. Applicants desired interviews on weekdays
      and geographic coordination of interviews. CONCLUSIONS: Integrated plastic
      surgery residency training is highly competitive, with the number of interview
      invitations correlating with academic performance and, to a lesser extent,
      research. Applicant feedback from this survey can be used to improve the
      application and interview process.

PMID- 19407636
TI  - Ethnic diversity remains scarce in academic plastic and reconstructive surgery.
AB  - BACKGROUND: Plastic surgery has been dedicated to advancing academic surgery in
      education, research, innovation, and patient care. Thus, as U.S. health care
      disparities persist, it would be befitting for plastic surgery to assume the lead
      in alleviating these disparities. As part of a multifaceted approach to
      ameliorate health care disparities, increasing diversity in the health care
      workforce will be imperative. Investigating the demographics of the U.S. plastic
      surgery residents and faculty can bring attention to a deficit that, if
      corrected, could benefit the field and improve the entire health care system.
      METHODS: Medical students, plastic surgery residents/fellows, and plastic surgery
      faculty demographic information from 1966 to 2006 was analyzed from the
      Association of American Medical Colleges' data files. RESULTS: Caucasians
      encompass 68.7 percent of U.S. plastic surgery residents/fellows, while Asian-,
      African-, and Latino-Americans encompass 20.9, 3.7, and 6.2 percent,
      respectively. Caucasians comprise 74.9 percent of academic plastic surgeons,
      while Asian-, African-, and Latino-Americans comprise 10.9, 1.4, and 3.6 percent,
      respectively. Caucasians constitute 82.0 percent of tenured full professors,
      while Asian-, African-, and Latino-Americans constitute 4.9, 1.6, and 4.9
      percent, respectively. In 2004, African-Americans and Latino-Americans comprised
      3.6 percent and 5.7 percent of all U.S. plastic surgeons, but only 1.5 percent
      and 4.9 percent of plastic academicians, respectively. CONCLUSIONS: Over the last
      40 years, plastic surgery has been ineffective in adequately increasing the
      number of minority residents and faculty. Expanding the number of minority
      academic plastic surgeons could establish a health care environment more
      accommodating to minority patients, increase studies highlighting minority health
      needs, and provide additional role models and mentors.

PMID- 19407640
TI  - Induced restrictive lung disease secondary to tissue expansion in ischiopagus
      conjoined twins (invited discussion).

PMID- 19407642
TI  - Aquamid: where is the reality?

PMID- 19407643
TI  - Suspension of the lower lid in paralytic lagophthalmos.

PMID- 19407644
TI  - A prospective, randomized, double-blind, controlled trial of continuous local
      anesthetic infusion in cosmetic breast augmentation: what lies beyond data?

PMID- 19407646
TI  - Breast lift and reduction: how we do it.

PMID- 19407648
TI  - Use of preoperative Doppler for distally based sural flap planning.

PMID- 19407650
TI  - The dilemma of the expert witness: part II.

PMID- 19407653
TI  - Devazepide, a nonpeptide antagonist of CCK receptors, induces apoptosis and
      inhibits Ewing tumor growth.
AB  - The Ewing family of tumors is a group of highly malignant tumors that mainly
      arise in bone and most often affect children and young adults in the first two
      decades of life. Despite the use of multimodal therapy, the long-term disease
      free survival rate of patients with Ewing tumors is still disappointingly low,
      making the discovery of innovative therapeutic strategies all the more necessary.
      We have recently shown that cholecystokinin (CCK), a neuroendocrine peptide,
      involved in many biological functions, including cell growth and proliferation,
      is a relevant target of the EWS/FLI1 oncoprotein characteristic of Ewing tumors.
      CCK silencing inhibits cell proliferation and tumor growth in vivo, suggesting
      that CCK acts as an autocrine growth factor for Ewing cells. Here, we analyzed
      the impact of two CCK receptor antagonists, devazepide (a CCK1-R antagonist) and
      L365 260 (a CCK2-R antagonist), on the growth of Ewing tumor cells. Devazepide
      (10 micromol/l) inhibited cell growth of four different Ewing tumor cells in
      vitro (range 85-88%), whereas the effect of the CCK2-R antagonist on cell growth
      was negligible. In a mouse tumor xenograft model, devazepide reduced tumor growth
      by 40%. Flow cytometry experiments showed that devazepide, but not L365 260,
      induced apoptosis of Ewing tumor cells. In summary, devazepide induces cell death
      of Ewing tumor cells, suggesting that it could represent a new therapeutic
      approach in the management of Ewing's tumor patients.

PMID- 19407654
TI  - Characterization of high-grade ductal carcinoma in situ with and without
      regressive changes: diagnostic and biologic implications.
AB  - Regressive changes (RC) have been described in malignant melanoma, carcinomas of
      the prostate and cervix. The presence of RC in these neoplasms may signify some
      degree of host response to tumor and seems to be a sign of poor prognosis for
      some neoplasms. RC in breast cancer is vaguely defined in the older literature.
      We have observed periodically similar RC in a subset of high-grade ductal
      carcinoma in situ (HGDCIS) in breast specimens. The aim of our study is to
      demonstrate how to recognize RC in the diagnostic setting and an attempt to
      understand the biologic behavior in this subset of HGDCIS cases. Fifty-nine cases
      of HG-DCIS (35 cases with RC and 24 cases without RC) were included. We defined
      RC in our study as demonstrating thick periductal fibrosis, dense lymphocytic
      infiltrate, and a thin rim of intact neoplastic cells. A short panel of
      immunomarkers to study this entity included myoepithelial markers. Reduced
      expression of myoepithelial markers (p63 and smooth muscle heavy chain myosin)
      were seen more frequently in the HGDCIS group with RC than without RC cases.
      Invasion as well as metastatic disease was seen in association with HGDCIS with
      RC nearly 4 times as often. It is also critically important to recognize HGDCIS
      RC for diagnostic purposes, as the differential diagnosis of RC includes, benign
      associations such as papilloma, fibrocystic changes and periductal mastitis.
      HGDCIS-RC may also be a sign of an aggressive phenotype than other HGDCIS
      subtypes. Further outcome studies are necessary to determine if it has a clinical
      impact akin to other tumors with RC.

PMID- 19407655
TI  - Survivin expression quantified by Image Pro-Plus compared with visual assessment.
AB  - Over the past decades, immunohistochemistry has gained significance and already
      taken a crucial position in diagnosis of diseases and prognosis of patients.
      However, manual interpretation of immunohistochemistry and reproducibility of the
      scoring systems can be highly subjective. In the article, the immunohistochemical
      staining of survivin in 98 rectal cancers was analyzed by using Image Pro-Plus
      (IPP) [3 parameters: density mean, area sum, and integrated optical density
      (IOD)] and the results were compared with visual assessment (2 parameters:
      intensity and percentage). The correlations between the 2 methods were examined,
      significant correlations were observed between density mean and staining
      intensity (Spearman correlation coefficient, rs=0.806, P<0.001), IOD and staining
      intensity (rs=0.914, P<0.001), area sum and staining percentage (rs=0.883,
      P<0.001), IOD and staining percentage (rs=0.884, P<0.001). There was no
      significant difference between survivin expression and clinicopathologic
      variables (P>0.05) by visual assessment. However, by IPP analysis, both the
      density mean and IOD were higher in better-differentiated cancers than in worse
      differentiated ones (P=0.02 and 0.03). There was a substantial agreement between
      the 2 methods. Density mean and IOD of IPP were representative parameters to
      assess the immunostaining quantification, and increased sensitivity in scoring
      and provided a more reliable and reproducible analysis of protein expression,
      especially, more information of the protein expression in relation to
      clinicopathologic variables can be provided by IPP analysis.

PMID- 19407656
TI  - Role of HERV-W syncytin-1 in placentation and maintenance of human pregnancy.
AB  - Over half of human genome contains retroelements, including retrotransposons,
      retroviruses, and other elements. Human endogenous retroviruses (HERVs) comprise
      about 8% of human genome. The products of 2 of 16 identified genes of HERV-W seem
      to play a pivotal role in the placentation. These 2 genes are HERV-W env
      glycoprotein (syncytin-1) and HERV-FRD env glycoprotein (syncytin-2). It has been
      shown previously that syncytin-1 mediates cell-cell fusions of cytotrophoblasts
      into syncytiotrophoblasts. In addition, HERV-W env contains an immunosuppressive
      region that may prevent rejection of a semiallogenic fetus from the mother's
      immune system. We analyzed 40 full-term placental tissues to localize the
      expression of syncytin-1-ISR by immunohistochemical staining and by reverse
      trancscriptase (RT) in situ polymerase chain reaction (PCR). Both the
      immunostaining and in situ RT-PCR showed strong expression of syncytin-1 in the
      syncytiotrophoblast layer from the full-term placental tissues. To further
      analyze the mechanism of early embryo HERV-W env activation, we utilized a HTR
      8/SVneo cell line developed from first trimester human trophoblasts and subjected
      them to various physiologic concentrations of maternal hormones. Quantitative RT
      PCR analyses demonstrated that exposure to progesterone significantly upregulated
      the HERV-W env expression, whereas several other hormones apparently played
      lesser roles. In conclusion, our findings suggest that expression of syncytin-1
      (HERV-W env) in utero is expressed exclusively in the syncytiotrophoblast layer
      and is upregulated by progesterone.

PMID- 19407657
TI  - Anxiolytic-like effect of noradrenaline microinjection into the dorsal
      periaqueductal gray of rats.
AB  - The brain noradrenergic system has been implicated in the expression of defensive
      behaviors elicited by acute stress. The dorsal periaqueductal gray area (dPAG) is
      a key structure involved in the behavioral and cardiovascular responses elicited
      by fear and anxiety situations. Although there are noradrenergic terminals in the
      dPAG, few studies have investigated the role of noradrenaline (NA) in the dPAG on
      anxiety modulation. The aim of this study was to evaluate the effect of NA
      microinjection into the dPAG of rats subjected to two animal models of anxiety,
      the elevated plus-maze and the Vogel conflict test. Male Wistar rats implanted
      with a guide cannula aimed at the dPAG received microinjections of NA (3, 15, or
      45 nmol/0.05 microl) or artificial cerebral spinal fluid into the dPAG
      immediately before being exposed to the elevated plus-maze or the Vogel conflict
      test. NA increased the exploration of the open arms and the number of enclosed
      arm entries in the elevated plus-maze. The increase in open arm exploration
      remained significant after being subjected to an analysis of covariance using the
      latter variable as covariate. Moreover, the NA microinjection into the dPAG did
      not increase general exploratory activity of animals subjected to the open-field
      test, indicating that the increase in open arm exploration cannot be attributed
      to a nonspecific increase in exploratory activity. In the Vogel test, the NA
      microinjection into the dPAG increased the number of punished licks without
      changing the number of nonpunished licks or interfering with the tail-flick test.
      The results, therefore, indicate that the NA microinjection into the dPAG
      produces anxiolytic-like effects, suggesting its possible involvement in the
      anxiety modulation.

PMID- 19407658
TI  - International open-label studies to assess the efficacy and safety of single-pill
      amlodipine/atorvastatin in attaining blood pressure and lipid targets recommended
      by country-specific guidelines: the JEWEL programme.
AB  - BACKGROUND: Single-pill amlodipine/atorvastatin targets the two most common
      modifiable cardiovascular risk factors, hypertension and dyslipidaemia. We
      evaluated the clinical utility of this single pill to help patients across Europe
      and Canada achieve country-specific targets for blood pressure (BP) and low
      density lipoprotein cholesterol (LDL-C). DESIGN: Two 16-week, open-label studies
      conducted in 122 study centres across the United Kingdom and Canada (JEWEL 1) and
      113 centres across 11 European countries (JEWEL 2). METHODS: Patients with
      uncontrolled BP and controlled/uncontrolled LDL-C qualifying for treatment
      according to local governing guidelines were administered single-pill
      amlodipine/atorvastatin with appropriate lifestyle modification. Eight dosages of
      amlodipine/atorvastatin (5/10-10/80 mg) were titrated to achieve country-specific
      BP and LDL-C targets. The primary outcome was the percentage of patients reaching
      country-specific BP and LDL-C targets in 16 weeks. RESULTS: Among 2245 patients
      enrolled in the studies (JEWEL 1, n = 1138; JEWEL 2, n = 1107), 62.9% in JEWEL 1
      and 50.6% in JEWEL 2 achieved both country-specific BP and LDL-C goals. BP was
      reduced by 20.4/10.7 and 21.8/12.6 mmHg in JEWEL 1 and JEWEL 2, respectively, and
      reductions in LDL-C were 0.90 mmol/l (34.8 mg/dl) and 1.09 mmol/l (42.2 mg/dl),
      respectively. The most common adverse events were peripheral oedema (11.0%),
      joint swelling (2.9%) and headache (2.9%), of which, only oedema was linked to
      study treatment. CONCLUSION: Single-pill amlodipine/atorvastatin is an effective
      and well-tolerated treatment, which in a real-world setting helped more than half
      of the patients achieve both BP and LDL-C targets as recommended by local
      guidelines. Although fewer patients met their goals in JEWEL 2 than JEWEL 1,
      reductions in BP and LDL-C were slightly greater in JEWEL 2, suggesting that the
      observed differences are likely because of more stringent targets in Europe than
      in the UK/Canada.

PMID- 19407659
TI  - Telehealth interventions for the secondary prevention of coronary heart disease:
      a systematic review.
AB  - Coronary heart disease (CHD) is a leading cause of death globally. Despite proven
      health benefits and international recommendations, attendance at cardiac
      rehabilitation programs is poor. Telehealth (phone, Internet, and videoconference
      communication between patient and health-care provider) has emerged as an
      innovative way of delivering health interventions. This review aimed to determine
      telehealth effectiveness in CHD management. Study design includes systematic
      review with meta-analysis. Randomized controlled trials evaluating telehealth
      interventions in patients with CHD were identified by searching multiple
      electronic databases, reference lists, relevant conference lists, gray
      literature, and key-word searching of the Internet. Studies were selected if they
      evaluated a telephone, videoconference, or web-based intervention, provided
      objective measurements of mortality, changes in multiple risk factor levels or
      quality of life. In total, 11 trials were identified (3145 patients). Telehealth
      interventions were associated with nonsignificant lower all-cause mortality than
      controls [relative risk=0.70, 95% confidence interval (CI)=0.45-1.1; P=0.12].
      These interventions showed a significantly lower weighted mean difference (WMD)
      at medium long-term follow-up than controls for total cholesterol (WMD=0.37
      mmol/l, 95% CI=0.19-0.56, P<0.001), systolic blood pressure (WMD=4.69 mmHg, 95%
      CI=2.91-6.47, P<0.001), and fewer smokers (relative risk = 0.84, 95% CI=0.65
      0.98, P = 0.04). Significant favorable changes at follow-up were also found in
      high-density lipoprotien and low-density lipoprotein. In conclusion, telehealth
      interventions provide effective risk factor reduction and secondary prevention.
      Provision of telehealth models could help increase uptake of a formal secondary
      prevention by those who do not access cardiac rehabilitation and narrow the
      current evidence-practice gap.

PMID- 19407660
TI  - Are hip-specific items useful in a quality of life questionnaire for patients
      with hip fractures?
AB  - Researchers measure the significance of hip fracture by the patient's impairment.
      The patient's quality of life (QOL) is usually also substantially affected.
      However, there is no specific quality of life (QOL) questionnaire for patients
      with hip fractures. This study was designed to determine whether adding a new set
      of specific questions about hip fracture to the World Health Organization Quality
      of Life Questionnaire would be helpful for patients with hip fractures. Three
      hundred and fifty-two patients were interviewed over the telephone. Three of the
      four initial items were chosen for statistical analysis. The Cronbach's alpha of
      the four domains (physical, psychological, social, and environmental) ranged from
      0.84 to 0.92 (P<0.01), and that of the new physical domain (PD) (adding the three
      new items) was 0.94 (P<0.01). Test-retest correlations of the three new items and
      all domains exceeded 0.66 (P<0.01). Criteria-related validity of the three new
      items ranged from 0.52 to 0.65 (P<0.05). The correlations between the new PD and
      the overall QOL and general health (0.70-0.78) were slightly lower than those
      (0.72-0.80) between the standard PD and the new items. A four-factor model was
      confirmed after factor analysis was conducted. In conclusion, adding three new
      items to the questionnaire led to only limited improvement in reliability and
      validity. The World Health Organization Quality of Life Questionnaire is
      sufficient for measuring QOL in patients with hip fractures.

PMID- 19407661
TI  - Visceral obesity and hypoadiponectinemia are significant determinants of hepatic
      dysfunction: An epidemiologic study of 3827 Japanese subjects.
AB  - BACKGROUND AND AIM: Adiponectin is an anti-inflammatory and insulin-sensitizing
      adipocytokine, and its serum concentrations are reduced in obesity with visceral
      fat accumulation. Visceral fat accumulation is an independent determinant of
      elevated serum liver enzymes. Hypoadiponectinemia plays important roles in the
      clinical progression of nonalcoholic steatohepatitis. The aim of this study was
      to evaluate the relation between visceral fat area (VFA), serum adiponectin
      concentration, and biochemical liver tests, such as aspartate aminotransferase,
      alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) in normal
      subjects. METHODS: The study group comprised 3827 Japanese subjects [mean age+/
      SD; 47.6+/-10.7 y: 2854 males (48.4+/-10.7 y), 973 females (45.3+/-10.1 y)], who
      underwent annual health checkup in 2004. In addition to parameters measured in
      the annual health checkup, VFA and serum adiponectin concentration were measured
      by the bioelectrical impedance analysis method and a latex particle-enhanced
      turbidimetric assay system, respectively. RESULTS: Pearson's correlation analysis
      showed a significant correlation between VFA and the levels of the above 3 liver
      enzymes in both sexes, and a significant negative correlation between adiponectin
      and all biochemical liver tests in men and with ALT and GGT in women. Stepwise
      multiple regression analysis showed that VFA was a significant determinant of
      serum liver tests in both sexes. Moreover, serum adiponectin concentration
      significantly and negatively influenced male ALT and GGT and female GGT.
      CONCLUSIONS: Both visceral obesity and hypoadiponectinemia are significant
      determinants of subtle and asymptomatic hepatic dysfunction in normal Japanese
      subjects.

PMID- 19407662
TI  - A comparative study of proton-pump inhibitor tests for Chinese reflux patients in
      relation to the CYP2C19 genotypes.
AB  - BACKGROUND: The proton-pump inhibitor (PPI) test has been proposed as a valuable
      tool for diagnosing gastroesophageal reflux disease in Western populations.
      GOALS: We aim to compare the diagnostic accuracy of the PPI test using
      rabeprazole and pantoprazole in a Chinese population with a higher prevalence of
      poor PPI metabolization. STUDY: After diagnostic endoscopy, patients with
      gastroesophageal reflux disease symptoms were randomly assigned to a 2-week test
      with rabeprazole (20 mg b.i.d.) or pantoprazole (40 mg b.i.d.). Therapeutic
      response was assessed with a 5-grade daily record. Genotypes of cytochrome P450
      (CYP) 2C19 polymorphism were determined. RESULTS: Of the 178 patients who
      completed the study, 92 (51.7%) had erosive esophagitis and 78 (48.3%) were
      endoscopy-negative reflux disease. On the basis of 50% reduction of symptoms,
      there was a nonsignificant difference of diagnostic performances between
      rabeprazole and pantoprazole. For the CYP2C19 genotypes, 138 (87.3%) were
      determined to be extensive metabolizers (EMs) and 20 (12.7%) were poor
      metabolizers (PMs). When comparing the EMs and PMs, the diagnostic specificity in
      the prediction of erosive esophagitis was higher in the EMs (57.6% vs. 20.0%,
      P=0.040), as was the accuracy (74.6% vs. 50.0%, P=0.023). There were no
      differences in the sensitivity, positive predictive value, or negative predictive
      value. CONCLUSIONS: CYP2C19 genotypic polymorphism was related to a higher
      possibility of false-positive results for patients who metabolized PPI poorly.
      High-dose rabeprazole and pantoprazole showed a similar diagnostic performance.

PMID- 19407663
TI  - Smokers as a high-risk group: data from a screening population.
AB  - GOAL: To determine the number of pack-years exposure associated with a 2-fold
      increase risk for significant colorectal neoplasia and to examine the risk of
      smoking in younger patients. BACKGROUND: Cigarette smoking has been shown to be a
      significant risk factor for colorectal neoplasia and may be used to stratify
      patients for screening or triaging of screening resources. However, more
      information is needed regarding the amount of exposure required to significantly
      increase by 2-fold an individual's risk for colorectal neoplasia. METHODS: Data
      collected for 2707 patients presenting for screening colonoscopy included tobacco
      use measured in pack-years and known risk factors for colorectal neoplasia. Our
      outcome was endoscopically detected significant colorectal neoplasia that
      included large (>1 cm) tubular adenomas, villous adenomas, multiple (3 or more)
      adenomas, high-grade dysplasia, and adenocarcinoma. RESULTS: Patients who smoked
      more than 30 pack-years were more than 2 times more likely to have significant
      colorectal neoplasia than patients who never smoked (odds ratio: 2.40; 95%
      confidence interval: 1.65-3.50). For patients aged 40 to 49 years, smokers were
      more likely than nonsmokers to have significant colorectal neoplasia (odds ratio:
      2.71; 95% confidence interval: 1.05-6.97). CONCLUSIONS: Patients who have smoked
      more than 30 pack-years had a more than 2-fold increase for significant
      colorectal neoplasia as compared with nonsmokers. The increased risk was also
      observed in younger patients. Our data have implications for screening
      guidelines.

PMID- 19407664
TI  - Clinical and endoscopic data in juvenile polyposis syndrome in preadolescent
      children: a multicenter experience from the United States.
AB  - OBJECTIVES: Juvenile polyposis syndrome (JPS) is a hereditary syndrome associated
      with several germline mutations, and carries a significant risk for future cancer
      development. Clinical data of JPS in children are sparse, and clinical guidelines
      are mainly derived from the adult population. In the present study, we describe
      the largest series of children diagnosed with JPS and present clinical,
      endoscopical, and histologic data. METHODS: A retrospective study of children
      with JPS was performed. Children were recruited from 3 academic pediatric
      gastroenterology centers. Clinical presentation, colonoscopic description, and
      histologic and demographic data were collected at initial presentation and at
      each future colonoscopy surveillance. RESULTS: Thirty-six children were included
      in the study with a mean age of 7.35 years and male to female ratio of 1.25:1.
      The most common clinical presentation was gastrointestinal bleeding (100%).
      Family history of colon cancer was noted in 28% of children. A total of 366
      polyps were removed, of which 90.5% were pedunculated and 9.5% were sessile. Up
      to 4 colonoscopic, follow-up surveillances were documented: 21 children had 1
      surveillance, 10 children had 2 surveillances, 3 children had 3 surveillances,
      and 1 child had 4 surveillances. Polyps were evenly distributed throughout the
      colon. Most of the polyps (99.2%) had benign histology (inflammatory changes) and
      3 (0.8%) involved focal adenomatous changes. No adenocarcinoma was identified in
      any of the 366 polyps. CONCLUSIONS: Colonic polyps in JPS are rarely malignant
      during the pediatric age period. Our data suggest that the recommended colonic
      surveillance in children should be modified.

PMID- 19407665
TI  - The relationship between reproductive factors and metabolic syndrome in Korean
      postmenopausal women: Korea National Health and Nutrition Survey 2005.
AB  - OBJECTIVE: Postmenopausal women are known to have a higher prevalence of
      metabolic syndrome compared with premenopausal women. However, there are few
      studies that have investigated the effects of reproductive factors on metabolic
      syndrome in postmenopausal women. The objective of this study was to evaluate the
      association between reproductive factors and metabolic syndrome in postmenopausal
      women. METHODS: A total of 892 postmenopausal women who participated in the 2005
      Korean National Health and Nutrition Examination Survey were included. We
      determined an association between reproductive factors and metabolic syndrome.
      RESULTS: Using a multivariate logistic regression analysis, it was found that age
      at first birth was negatively associated with metabolic syndrome. Having the
      first baby at a later age was associated with a decreased risk of having
      metabolic syndrome (odds ratio, 0.95; 95% CI, 0.90-0.99). However, other
      reproductive factors including age at menarche, age at menopause, parity,
      lifetime estrogen exposure, years since menopause, number of pregnancies, history
      of lactation, and oral contraceptives or hormone therapy use were not associated
      with metabolic syndrome. CONCLUSIONS: Among various reproductive factors, age at
      first birth was negatively associated with metabolic syndrome in Korean
      postmenopausal women.

PMID- 19407667
TI  - Efficacy of ossein-hydroxyapatite complex compared with calcium carbonate to
      prevent bone loss: a meta-analysis.
AB  - OBJECTIVE: There is increasing evidence to suggest that ossein-hydroxyapatite
      complex (OHC) is more effective than calcium supplements in maintaining bone
      mass. The aim of this meta-analysis was to determine whether OHC has a different
      clinical effect on bone mineral density (BMD) compared with calcium carbonate
      (CC). METHODS: A meta-analysis of randomized controlled clinical trials was
      carried out to evaluate the efficacy of OHC versus CC on trabecular BMD. We
      identified publications on clinical trials by a search of electronic databases,
      including MEDLINE (1966-November 2008), EMBASE (1974-November 2008), and the
      Cochrane Controlled Clinical Trials Register.The primary endpoint was percent
      change in BMD from baseline. Data were pooled in a random-effects model, and the
      weighted mean difference was calculated. A sensitivity analysis that excluded
      trials without full data was performed. RESULTS: Of the 18 controlled trials
      initially identified, 6 were included in the meta-analysis. There was no
      significant heterogeneity among the included trials. The percent change in BMD
      significantly favored the OHC group (1.02% [95% CI, 0.63-1.41], P < 0.00001).
      These results were confirmed in the sensitivity analysis. CONCLUSIONS: OHC is
      significantly more effective in preventing bone loss than CC.

PMID- 19407668
TI  - Biphasic effects of neonatal allopregnanolone on striatal dopamine metabolism.
AB  - Neurosteroids are known to modulate the development of the mesocorticolimbic
      system. We examined the effects of low (1 mg/kg) and high (10 mg/kg) doses of
      allopregnanolone on monoamine metabolism during the neonatal period (postnatal
      days 3-7) in rats. At 10 weeks of age, increases in homovanillic acid/dopamine
      (DA) ratios were found in the striatum in both allopregnanolone-treated groups
      compared with control rats. However, striatal DA levels decreased only in the low
      allopregnanolone group and striatal homovanillic acid levels increased only in
      the high-allopregnanolone group. Allopregnanolone did not significantly affect
      cortical DA metabolism, or cortical or striatal serotonin metabolism. Data
      indicate that neonatal allopregnanolone treatment has a biphasic effect on
      striatal DA metabolism.

PMID- 19407666
TI  - Effect of L-methionine on hot flashes in postmenopausal women: a randomized
      controlled trial.
AB  - OBJECTIVE: Based on a common mechanism of action with gabapentin, we investigated
      the effects of L-methionine on hot flashes in postmenopausal women. METHODS:
      After a 1-week baseline period, 51 postmenopausal women experiencing at least
      five moderate-severe hot flashes per day were randomized to one of three groups
      in a 13:13:25 ratio: placebo/placebo, placebo/L-methionine, or L-methionine/L
      methionine, respectively (phase 1/phase 2). Phase 1 was 12 weeks long, and phase
      2 was 8 weeks long. Participants took 1 g PO BID in phase 1 and 2 g PO BID in
      phase 2 of either L-methionine or placebo. All participants also took folate 1 mg
      and methylcobalamin 0.5 mg a day to help minimize the L-methionine-induced
      elevation in serum homocysteine. The primary outcome variable was the percent
      change in hot flash composite score from baseline to week 12 obtained from
      participants' daily hot flash diaries. RESULTS: In phases 1 and 2, there were no
      significant differences between the L-methionine and placebo groups for any of
      the hot flash outcome measures. At week 12, there was a mean of 37.4% decrease in
      hot flash composite score compared with baseline in the L-methionine group and a
      mean of 33.4% decrease in the placebo group (P = 0.60). There were expected
      significant increases in fasting serum homocysteine (1.7 and 5.8 micromol/L) and
      fasting serum methionine (13.9 and 22.3 micromol/L) at weeks 12 and 20,
      respectively, associated with the two doses of L-methionine therapy relative to
      placebo therapy. CONCLUSIONS: L-methionine therapy seems to be ineffective in the
      treatment of hot flashes in postmenopausal women.

PMID- 19407669
TI  - Emotional influences on time perception: evidence from event-related potentials.
AB  - This study examined the influence of emotion on time perception and its neural
      correlates by measuring event-related potentials. Participants were asked to
      discriminate a previously memorized 700 ms 'standard' duration from 490, 700 and
      910 ms, which were presented by emotional and neutral faces. The results showed
      decreased contingent negative variation potentials, which index timing, for
      emotional conditions versus the neutral condition. In addition, under the
      emotional conditions, the P160 and P240 amplitudes were enhanced and the N230
      amplitude was decreased. These findings suggest that temporal processing can be
      modulated by emotion, even within 200 ms of the stimulus onset, and that the
      attentional bias for emotion attenuates the cognitive resources for time
      perception.

PMID- 19407674
TI  - Doctors with a special interest in back pain have poorer knowledge about how to
      treat back pain.
AB  - STUDY DESIGN: We conducted an observational study using mailed questionnaires to
      3 random samples of general practitioners from Victoria and New South Wales,
      Australia in 1997, 2000, and 2004. OBJECTIVE: To determine whether general
      practitioners' beliefs about low back pain (LBP) differ according to whether they
      have a special interest in back pain, musculoskeletal, or occupational medicine;
      and whether these beliefs are modified by having had continuing medical education
      (CME) about back pain in the previous 2 years. SUMMARY OF BACKGROUND DATA:
      Physician surveys continue to demonstrate that general practitioners only
      partially manage LBP in an evidence-based way. Identified barriers to changing
      physician behavior, in regard to management of back pain, have included patient
      factors such as their past back pain experiences and preferences for care as well
      as physician beliefs about the association of pain and activity; although the
      influence of physician special interests has not been studied. METHODS: Back pain
      beliefs of different subsets (special interests vs. no special interests and CME
      vs. no CME) were compared using relative risks (RRs) adjusted for state and
      survey. The analysis was then repeated including all special interests and recent
      back pain CME in the model. RESULTS: Responses were received from 3831 general
      practitioners (overall response rate [RR]: 38.2%). Physicians with a special
      interest in LBP were more likely to believe that complete bed rest and avoidance
      of work is appropriate for acute low back pain (RR: 1.89 [95% CI: 1.53-2.33] and
      1.55 [95% CI: 1.31-1.83], respectively) and lumbar spine radiographs are useful
      (RR: 1.36 [95% CI: 1.21-1.51]). The disparity between those with and without a
      special interest in LBP was still evident after adjusting for the presence of
      other special interests and recent CME. After adjusting for the presence of other
      special interests and recent CME, there were no important differences in back
      pain beliefs between those with and without a special interest in musculoskeletal
      medicine, while those with a special interest in occupational medicine and those
      who had received recent CME had better beliefs. CONCLUSION: A special interest in
      back pain is associated with back pain management beliefs contrary to the best
      available evidence. This has serious implications for management of back pain in
      the community.

PMID- 19407672
TI  - Copy number variations associated with idiopathic autism identified by whole
      genome microarray-based comparative genomic hybridization.
AB  - OBJECTIVES: Autism spectrum disorder (ASD) has been thought to have strong
      genetic background, but major contributing genes or associated molecular-genetic
      pathways are yet to be identified. To explore the idiopathic ASD-associated copy
      number variations (CNVs), we conducted case-control study using whole-genome copy
      number analysis. METHODS: Whole-genome microarray-based comparative genomic
      hybridization was carried out on 28 children (24 boys and four girls) diagnosed
      as ASD and 62 Korean adults (45 males and 17 females) without any signs of
      abnormalities and family history of genetic disorders as normal controls.
      Fluorescence in-situ hybridization and capillary electrophoresis-single-strand
      conformational polymorphism were used for quantitative verification of the ASD
      associated CNVs. RESULTS: Thirty-eight CNVs were identified. Among them, the
      distributions of copy number loss CNVs on 8p23.1 (odds ratio: 5.1, 95% confidence
      interval: 1.7-14.5, P=0.003) and on 17p11.2 (odds ratio: uncalculable because of
      zero cell, P=0.008) were found to be significantly different between ASD and
      control groups. DEFENSIN family occurs in a cluster at 8p23.1 region.
      Fluorescence in-situ hybridization and capillary electrophoresis-single-strand
      conformational polymorphism coherently showed reduced copy number of DEFENSIN in
      cases with 8p23.1 copy number loss CNV, which validated microarray-based
      comparative genomic hybridization results; but there are no known coding genes in
      the CNV on 17p11.2. CONCLUSION: Our approach as well as results can help to
      elucidate the genetic mechanism of idiopathic ASD.

PMID- 19407675
TI  - High-resolution magnetic resonance imaging and 18FDG-PET findings of the cervical
      spinal cord before and after decompressive surgery in patients with compressive
      myelopathy.
AB  - STUDY DESIGN: Evaluation of cervical spinal cord (CSC) of patients with
      compressive myelopathy by magnetic resonance imaging (MRI) and high-resolution
      (18F)fluoro-deoxyglucose (18FDG) positron emission tomography (PET). OBJECTIVE:
      To determine changes in morphology, intramedullary signal intensity, and glucose
      metabolic rate in CSC after decompression, and to assess the utility of 18FDG-PET
      in evaluation of patients with cervical myelopathy. SUMMARY OF BACKGROUND DATA:
      The significance of CSC enlargement after decompression and signal intensity
      changes within the cord remain elusive. No data are available on metabolic
      activity of the compressed CSC. Only a few studies have examined correlation
      between high-resolution MRI and 18FDG-PET neuroimaging in cervical myelopathy.
      METHODS: We studied 24 patients who underwent cervical decompressive surgery in
      terms of postoperative neurologic improvement and changes in MRI and 18FDG-PET.
      Neurologic status was assessed by the Japanese Orthopedic Association scoring
      system (17-point scale). Signal intensity change in the cord was qualitatively
      assessed on both T1- and T2-weighted images. The transverse area of the CSC on
      MRIs and glucose metabolic rate (standardized uptake value [SUV]) from 18FDG-PET
      were measured digitally. RESULTS: Neurologic improvement correlated with
      preoperative CSC transverse area at maximal compression (P < 0.01) and at follow
      up (P < 0.001) and with mean SUV before surgery (P < 0.01) and at follow-up (P <
      0.05). Preoperative signal intensity change on MRIs (low intramedullary signal
      intensity abnormality on T1-weighted image and high intramedullary on T2-weighted
      image) correlated negatively with neurologic improvement rate (P < 0.05). The
      transverse area of the CSC was significantly smaller after surgery in patients
      with preoperative MRI signal intensity changes (P < 0.05). The SUV at follow-up
      tended to normalize in association with neurologic improvement. CONCLUSION: Our
      results showed that postoperative neurologic improvement in patients with
      cervical compressive myelopathy correlated with increased transverse area of the
      spinal cord, signal intensity change on both T1- and T2-weighted image, and the
      mean SUV.

PMID- 19407676
TI  - Peroxynitrite induces gene expression in intervertebral disc cells.
AB  - STUDY DESIGN: In vitro stimulation of human intervertebral disc (IVD) cells.
      OBJECTIVE: To investigate the oxidative/nitrosative effects of peroxynitrite on
      human nucleus pulposus (NP) cells. SUMMARY OF BACKGROUND DATA: Peroxynitrite is
      an important tissue-damaging species generated at sites of inflammation and
      degeneration. The aim of this study was to examine the effects of
      oxidative/nitrosative stress caused by peroxynitrite and the peroxynitrite donor
      SIN-1 in human NP cells. METHODS: Degenerated human IVD tissue was analyzed for
      nitrosylation by immunofluorescence. In addition, human NP cells were isolated
      from IVDs, expanded and stimulated either with peroxynitrite itself or a stable
      peroxynitrite donor (SIN-1). Nitrosylation, accumulation of intracellular
      reactive oxygen species, NF-kappaB nuclear translocation, and cell viability were
      analyzed by fluorescence. Gene expression of TNF-alpha, IL-1beta, IL-6, IL-8, and
      IL-10 was quantified by real-time (RT)-PCR. RESULTS: Degenerated IVD tissue
      showed strong nitrosylation, especially in the NP. Isolated human NP cells showed
      a strong signal for nitrosylation and intracellular reactive oxygen species on
      stimulation with peroxynitrite or SIN-1. NF-kappaB/p65 sustained nuclear
      translocation of NF-kappaB/p65 and stimulation of IL-1beta, IL-6, and IL-8
      expression was noted on treatment of cells with SIN-1. CONCLUSION: This study
      provides evidence that peroxynitrite may play a role in disc degeneration and
      discogenic back pain development by an increased synthesis of proinflammatory
      cytokines. Nuclear translocation of NF-kappaB was identified as the potential
      underlying pathway. Therefore, neutralizing peroxynitrite and its derivatives
      (e.g., via the use of antioxidants) may be a novel treatment option for
      discogenic back pain.

PMID- 19407677
TI  - The influence of preoperative back pain on the outcome of lumbar decompression
      surgery.
AB  - STUDY DESIGN: Prospective study with 12-month follow-up. OBJECTIVE: To examine
      how the relative severity of low back pain (LBP) to leg/buttock pain (LP)
      influences the outcome of decompression surgery for spinal stenosis. SUMMARY OF
      BACKGROUND DATA: Decompression surgery is a common treatment for lumbar spinal
      canal stenosis, with generally good outcome. However, concomitant LBP at
      presentation can make it difficult to decide whether decompression alone will
      result in a good overall outcome. METHODS: The Spine Society of Europe Spine
      Tango system was used to acquire the data from 221 patients. Inclusion criteria
      were lumbar degenerative spinal stenosis, first-time surgery, maximum 3 affected
      levels, and decompression as the only procedure. Before and 12 months after
      surgery, patients completed the multidimensional Core Outcome Measures Index
      (COMI; includes 0-10 LP and LBP scales); at 12 months, global outcome was rated
      on a Likert-scale and dichotomized into "good" and "poor" groups. RESULTS: There
      was a low but significant positive correlation between baseline LP-minus-LBP
      scores and both improvement in the multidimensional COMI score after 12 months (r
      = 0.21, P = 0.003) and the score on the 12-month global outcome scale (r = 0.19,
      P = 0.007). In the good outcome group, mean baseline LP was 2.3 (+/-3.7) points
      higher than LBP; in the poor group, the corresponding value was 0.8 (+/-3.4) (P =
      0.01 between groups). In multivariate regression analyses (controlling for age,
      gender, comorbidity), baseline LBP intensity was the most significant predictor
      of the 12-month COMI score, and preoperative LP-minus-LBP score of the global
      outcome (each P < 0.05). CONCLUSION: Overall, greater back pain relative to LP at
      baseline was associated with a significantly worse outcome after decompression.
      This finding seems intuitive, but has rarely been quantified in the many
      predictor studies conducted to date. Consideration of relative LBP and LP scores
      may assist in clinical decision-making and in establishing realistic patient
      expectations.

PMID- 19407678
TI  - An open-label randomized trial to determine the most effective regimen of vaginal
      estrogen to reduce the prevalence of atrophic changes reported in postmenopausal
      cervical smears.
AB  - OBJECTIVE: Atrophic Papanicolaou (Pap) smears from postmenopausal women may be
      unsatisfactory for assessment or result in a false-positive diagnosis of a
      cytological abnormality. We investigated the effect of vaginal estrogen treatment
      before the Pap test on the odds of an atrophic smear. METHODS: An open-label
      randomized controlled trial was conducted to compare the proportion of atrophic
      Pap smears from postmenopausal women assigned to either (1) a regimen of one 25
      microg vaginal estradiol tablet inserted nightly for five nights before their Pap
      test, (2) a single 25-microg vaginal estradiol tablet before the test, or (3) a
      control group with no previous estrogen administration. All smears were reread
      and classified as atrophic or nonatrophic at the conclusion of the study by a
      single cytopathologist who was blinded to the study arms. RESULTS: One hundred
      fifty-four (94%) of the 164 postmenopausal women who consented to the study were
      included in the final analysis. Fifty-one women had received the five-night
      course of tablets, 50 had received one tablet, and 53 were assigned to the group
      with no previous estrogen use. The odds of an atrophic smear were significantly
      lower in women who used the five-night estrogen regimen than in women who did not
      use estrogen. The estimated odds ratio of an atrophic smear in the five-night
      regimen was 0.01 (95% CI, 0.03-0.26) compared with the no-estrogen control group.
      Moreover, using one tablet of estrogen had no significant effect on the
      likelihood of an atrophic smear compared with using none. The odds ratio of an
      atrophic smear in the single estrogen tablet group was 1.05 (95% CI, 0.48-2.29)
      compared with the no-estrogen group. CONCLUSIONS: The odds of an atrophic smear
      are significantly reduced for postmenopausal women who use a five-night regimen
      of vaginal estrogen before their Pap test.

PMID- 19407706
TI  - Optimal dosing of desvenlafaxine, new insights in gambling and anorexia, and
      caffeine-induced psychosis.

PMID- 19407679
TI  - Provider attributes associated with hormone therapy prescribing frequency.
AB  - OBJECTIVE: The aim of this study was to identify provider characteristics
      associated with hormone therapy prescribing. METHODS: The study design is cross
      sectional. In December 2005, we mailed surveys to providers practicing in two
      integrated healthcare delivery systems located in the northwestern and
      northeastern United States; 379 responded (74%) and 249 (49% of total) granted
      access to their automated data. Data included provider demographics, practice
      characteristics, and perceptions about hormone therapy. Provider-specific annual
      hormone therapy prescribing frequency was calculated as days supply of hormone
      therapy filled divided by the number of visits (among women aged 45-80 y).
      Factors associated with higher rates of hormone therapy prescribing were
      identified using bivariate and multivariate analyses. RESULTS: We report results
      separately for primary care providers (internists and family practitioners) and
      obstetrician/gynecologists because significant correlates differed in these two
      groups. For both primary care providers and obstetrician/gynecologists, in
      multivariate analyses, hormone therapy prescribing varied by site (P < or =
      0.002) and years at the healthcare organization (P < or = 0.01). For primary care
      providers only, higher hormone therapy prescribing was associated with reported
      expert knowledge of the hormone therapy trials (P < or = 0.001). For
      obstetrician/gynecologists, higher hormone therapy prescription was related to
      feeling well prepared to counsel women on hormone therapy (P < or = 0.007),
      believing that the risks of estrogen with progestogen had been exaggerated (P =
      0.04), and seeing younger aged patients (P = 0.03). CONCLUSIONS: After the
      release of the Women's Health Initiative findings and practicing under similar
      clinical guidelines, hormone therapy prescribing is associated with providers'
      confidence, practice location, and time with a healthcare organization.

PMID- 19407707
TI  - Computerized neuropsychological assessments: pros and cons.

PMID- 19407708
TI  - Bipolar disorder: emotional dysregulation and neuronal vulnerability.
AB  - Bipolar disorder is clinically characterized by fluctuating affect, and
      neuropsychologically by impairment in executive functions. Such phenomena are
      consistent with the centrality of emotional dysregulation and impulsivity to
      bipolar disorder. They are also consistent with a key role for prefrontal
      subcortical (striatal-thalamic) and associated limbic circuitry in its mediation.
      Furthermore, there is growing data on the cellular mechanisms contributing to
      neuronal vulnerability in this mediating circuitry.

PMID- 19407709
TI  - Caffeine-induced psychosis.
AB  - As a competitive adenosine antagonist, caffeine affects dopamine transmission and
      has been reported to worsen psychosis in people with schizophrenia and to cause
      psychosis in otherwise healthy people. We report of case of apparent chronic
      caffeine-induced psychosis characterized by delusions and paranoia in a 47-year
      old man with high caffeine intake. The psychosis resolved within 7 weeks after
      lowering caffeine intake without use of antipsychotic medication. Clinicians
      might consider the possibility of caffeinism when evaluating chronic psychosis.

PMID- 19407711
TI  - An integrated analysis of the efficacy of desvenlafaxine compared with placebo in
      patients with major depressive disorder.
AB  - INTRODUCTION: To assess the efficacy of desvenlafaxine (administered as
      desvenlafaxine succinate) in outpatients with major depressive disorder. METHODS:
      A meta-analysis of individual patient data was performed on the complete set of
      registration trials (nine randomized, double-blind, placebo-controlled 8-week
      studies) of desvenlafaxine. Patients received fixed (50, 100, 200, or 400 mg/day;
      n=1,342) or flexible doses (100-400 mg/day; n=463) of desvenlafaxine or placebo
      (n=1,108). The primary efficacy variable was the 17-item Hamilton Rating Scale
      for Depression (HAM-D(17)); the primary intent to treat analyses used the last
      observation-carried-forward method. RESULTS: Significantly greater improvement
      with desvenlafaxine versus placebo on the HAM-D(17) total score was observed for
      the full data set (difference in adjusted means: -1.9; P<.001), each fixed-dose
      group (all P<.001), and the flexible-dose group (P=.024). Overall rates of HAM
      D1(17) response (> or =150% decrease from baseline score: 53% vs 41%) and
      remission (HAM-D(17) < or =7: 32% vs 23%) were significantly greater for
      desvenlafaxine versus placebo (all P<.001). Discontinuation rates due to adverse
      events increased with dose (4% to 18%; placebo: 3%). CONCLUSION: Desvenlafaxine
      demonstrated short-term efficacy for treating major depressive disorder across
      the range of doses studied. No evidence of greater efficacy was observed with
      doses >50 mg/day; a strong dose-response effect on tolerability was observed.

PMID- 19407712
TI  - Anorexia nervosa in identical triplets.
AB  - The cause of anorexia nervosa (AN) is unclear, but is likely multifactorial,
      including psychological, familial, environmental, societal, genetic, and other
      biological factors. This case report of identical 12-year-old female triplets
      simultaneously concordant for AN illustrates the importance of addressing all
      these components in evaluation and treatment, and the difficulty of determining
      the relative importance of each factor in the cause of an individual's eating
      disorder. An overly close relationship and competitiveness between the girls,
      treated at times as a triplet group rather than as individuals, as well as
      stressful family dynamics, were probably important antecedents to the girls' AN.
      The girls encouraged each other and competed to lose weight. Brief individual and
      family psychotherapy, parent counseling, nutritional counseling, and
      psychoeducation led to successful treatment. The triplets were encouraged in
      treatment to compete with and encourage each other to obtain treatment goals,
      including eating more healthily and achieving healthy weights. A literature
      review of AN twins studies is also presented, as these studies add to our
      understanding of the relative importance of shared genes and shared environment
      in the development of AN. These studies also add insight into treating
      individuals from families with multiple affected relatives.

PMID- 19407710
TI  - Disordered gambling among racial and ethnic groups in the US: results from the
      national epidemiologic survey on alcohol and related conditions.
AB  - INTRODUCTION: Prior research suggests that racial minority groups in the United
      States are more vulnerable to develop a gambling disorder than whites. However,
      no national survey on gambling disorders exists that has focused on ethnic
      differences. METHODS: Analyses of this study were based on the National
      Epidemiologic Survey on Alcohol and Related Conditions, a large (N=43,093)
      nationally representative survey of the adult (> or =18 years of age) population
      residing in households during 2001-2002 period. Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Edition-Text Revision diagnoses of pathological
      gambling, mood, anxiety, drug use, and personality disorders were based on the
      Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV
      Version. RESULTS: Prevalence rates of disordered gambling among blacks (2.2%) and
      Native/Asian Americans (2.3%) were higher than that of whites (1.2%). Demographic
      characteristics and psychiatric comorbidity differed among Hispanic, black, and
      white disordered gamblers. However, all racial and ethnic groups evidenced
      similarities with respect to symptom patterns, time course, and treatment seeking
      for pathological gambling. CONCLUSION: The prevalence of disordered gambling, but
      not its onset or course of symptoms, varies by racial and ethnic group. These
      varying prevalence rates may reflect, at least in part, cultural differences in
      gambling and its acceptability and accessibility. These data may inform the need
      for targeted prevention strategies for high-risk racial and ethnic groups.

PMID- 19407713
TI  - Pharmacologic and therapeutic strategies in treatment-resistant depression.
      Introduction and clinical presentations.

PMID- 19407714
TI  - Pharmacologic and therapeutic strategies in treatment-resistant depression.
      Augmentation strategies.

PMID- 19407715
TI  - Pharmacologic and therapeutic strategies in treatment-resistant depression.
      Switching antidepressants vs. conventional augmentation strategies.

PMID- 19407716
TI  - Major depressive disorder: barriers to treatment.

PMID- 19407717
TI  - Perceptions of efficacy, safety, and tolerability: impact on evaluating new
      treatments.

PMID- 19407718
TI  - Novel treatments for major depressive disorder.

PMID- 19407720
TI  - A new era for CNS Spectrums.

PMID- 19407719
TI  - Future drugs for the treatment of depression: the need to look beyond monoamine
      systems.

PMID- 19407721
TI  - Statins may act through increasing tissue plasminogen activator/plasmin activity
      to lower risk of Alzheimer's disease.

PMID- 19407722
TI  - Love and attachment: the psychobiology of social bonding.
AB  - Basic animal studies and human imaging studies have contributed to our
      understanding of the psychobiology of love and attachment. There are overlaps and
      distinctions in the neuronal circuitry of maternal love, romantic love, and long
      term attachment. In these circuits, important molecules, which have been
      demonstrated to play a role in the psychobiology of social bonding include
      dopamine, serotonin, opioids, oxytocin, and vasopressin. Particular genetic and
      environmental variations contribute to social-bonding phenotypes, consistent with
      an evolutionary perspective on the value of these behaviors. Advances in the
      psychobiology of social bonds have led to hypotheses about the pharmacotherapy of
      disorders of attachment.

PMID- 19407723
TI  - Non-Western therapies for affective disorders: in pursuit of open-minded
      considerations of concepts and applications.
AB  - INTRODUCTION: Complementary and alternative medicine (CAM) modalities are gaining
      popularity among patients in Western countries. They are especially popular among
      patients seeking treatment for mental and mood symptoms. Some CAMs are according
      to current Western approaches but have not achieved approval by regulatory
      agencies. Some other modalities are according to non-Western concepts of mental
      order and disorder. This installment of "The Well-Rounded Brain" will illuminate
      some non-Western concepts with an example of treatment modality for affective
      disorders, and compare them to conventional Western approach. METHODS: Principles
      of the Chinese concept of affective disorders and acupuncture modalities for
      their treatments are briefly described from a culturally sensitive perspective.
      RESULTS: Traditional Chinese medicine and current conventional Western medicine
      substantially differ in underlying concepts, development of treatment modalities,
      as well as their goals and implementation. CONCLUSION: Some non-Western concepts
      and treatment modalities have been meticulously and rigorously developed through
      trial and error, though the evidence for their efficacy and efficiency is not
      necessarily according to current Western standards. The consistent
      epidemiological demonstrations of the demand for CAM among patients suffering
      from mental disorders call for an open-minded, unbiased assessment of efficacy of
      non-Western treatment modalities for specific clusters of affective symptoms.

PMID- 19407725
TI  - Lifetime subthreshold mania is related to suicidality in posttraumatic stress
      disorder.
AB  - INTRODUCTION: Although the association between mood disorders, and particularly
      bipolar disorders, comorbidity and suicidality in posttraumatic (PTSD) patients
      is well established, less information is available on the impact of subsyndromal
      mood symptoms. The aim of the present study was, thus, to explore the frequency
      and relationship between subthreshold mood symptoms, assessed by a specific and
      validated questionnaire, and suicidality in PTSD patients. METHOD: Sixty-five
      PTSD outpatients without bipolar disorders and 65 healthy control subjects were
      asked to complete the Mood Spectrum-SR-Lifetime Version (MOODS-SR), a
      questionnaire exploring the presence of subthreshold affective symptoms. Logistic
      regression models were used to analyze the relationships between suicidality,
      explored by six items of the MOODS-SR combined and dichotomized to denote the
      presence or absence of suicidal ideations/plans and/or attempts, and the number
      of manic/hypomanic or depressive symptoms. RESULTS: Statistically significant and
      positive associations were found between the presence of manic/hypomanic and
      depressive symptoms and the likelihood of suicidal ideation or attempts.
      CONCLUSION: Besides depressive, even subthreshold manic/hypomanic features seem
      to be associated with higher suicidality in PTSD patients.

PMID- 19407726
TI  - Pathological love: impulsivity, personality, and romantic relationship.
AB  - INTRODUCTION: Pathological love (PL)--behavior characterized by providing
      repetitive and uncontrolled care and attention to the partner in a romantic
      relationship--is a rarely studied condition, despite not being rare and causing
      suffering. This study aims at investigating impulsivity, personality, and
      characteristics related to the romantic relationship in this population. METHODS:
      Eighty-nine individuals (50 with PL; 39 individuals with no psychiatric disorder)
      were compared regarding impulsivity, personality, type of attachment,
      satisfaction with romantic relationship, and love style. RESULTS: Individuals
      with PL have higher levels of impulsivity (P<.001; Barratt Impulsiveness Scale),
      higher self-transcendence, that is, are more unconventional and hold sense of
      communion with a wider reality (P<.001; Temperament and Character Inventory) and
      keep dissatisfactory romantic relationships (P<.001; Adapted Relationship
      Assessment Scale). CONCLUSION: Individuals with PL present personality traits and
      relationship aspects that must be taken into account in devising assessment and
      therapeutic strategies for this population.

PMID- 19407727
TI  - A decade of editing CNS spectrums: back to the future.

PMID- 19407724
TI  - A prospective pilot study of levetiracetam for body dysmorphic disorder.
AB  - INTRODUCTION: Body dysmorphic disorder (BDD) is an often severe disorder, but few
      treatment studies have been conducted. OBJECTIVE: This pilot study explored the
      efficacy and safety of the antiepileptic medication levetiracetam for BDD.
      METHODS: Seventeen subjects with Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition BDD participated in a 12-week open-label levetiracetam
      trial. Subjects were assessed at regular intervals with standard measures.
      RESULTS: In intent-to-treat analyses, scores on the Yale-Brown Obsessive
      Compulsive Scale Modified for BDD (BDD-YBOCS), the primary outcome measure,
      decreased from 32.5+/-4.7 at baseline to 21.5+/-11.0 at endpoint (P<.001).
      Approximately 60% (n=9) of subjects were responders (>30% decrease on the BDD
      YBOCS). The mean time to response was 4.6+/-2.8 (range: 2-10) weeks. Scores also
      significantly improved on the Brown Assessment of Beliefs Scale, the Hamilton
      Rating Scale for Depression, the Global Assessment of Functioning Scale, and the
      Social and Occupational Functioning Assessment Scale. Scores did not
      significantly improve on the Quality of Life Enjoyment and Satisfaction
      Questionnaire, the Beck Anxiety Inventory, or the Social Phobia Inventory. The
      mean endpoint dose of levetiracetam was 2,044.1+/-1,065.2 (range: 250-3,000)
      mg/day, and it was relatively well-tolerated. CONCLUSION: Randomized, double
      blind placebo-controlled studies of levetiracetam for BDD are needed to confirm
      these preliminary findings.

PMID- 19407728
TI  - Selective benefit of donepezil on oral naming in Alzheimer's disease in men
      compared to women.

PMID- 19407729
TI  - Applying the principles of adult learning to the teaching of psychopharmacology:
      overview and finding the focus.
AB  - Medical education in psychopharmacology can be designed according to modern
      principles of adult learning. The goal is to go beyond merely exposing learners
      to novel content, to the documentation that learning has occurred and that
      behaviors have changed, namely the upgrading of skills in clinical practice. The
      many aspects of this approach to medical education are discussed in overview
      here. Future installments of "Trends in Psychopharmacology" will periodically
      deal with specific aspects of the best practices for medical educators outlined
      here only in brief. This article considers whether the focus of medical education
      instructors should be the medical content they present, the medical educator that
      does the presenting, or the learner. The perspective here is that the focus of
      medical education should be the learner, and that the content should be
      structured and executed in a manner that facilitates learning instead of
      inhibiting it.

PMID- 19407730
TI  - An integrated analysis of the safety and tolerability of desvenlafaxine compared
      with placebo in the treatment of major depressive disorder.
AB  - INTRODUCTION: The safety and tolerability profiles of antidepressants can often
      influence the treatment choices of clinicians treating major depressive disorder.
      The purpose of this investigation was to characterize the safety and tolerability
      of desvenlafaxine (administered as desvenlafaxine succinate) in treating
      depression. METHODS: An integrated analysis of all short-term, randomized, double
      blind, placebo-controlled registration studies for major depressive disorder
      (four flexible-dose and five fixed-dose studies) was performed. Adult outpatients
      with major depressive disorder received desvenlafaxine doses ranging from 50-400
      mg/day or placebo for 8 weeks. Treatment-emergent adverse events, laboratory
      values, vital signs, and discontinuation symptoms were evaluated. In the subset
      of fixed-dose studies, dose-related effects were analyzed. RESULTS: In the
      overall population (placebo: n=1,116; desvenlafaxine: n=1,834), adverse events
      resulted in discontinuations in 3% of placebo-treated patients and 12% of
      desvenlafaxine-treated patients; in the subset of fixed-dose studies, the rates
      were 4% with placebo and increased with desvenlafaxine dose (50 mg/day: 4%; 400
      mg/day: 18%). The most common treatment-emergent adverse event was transient
      nausea that was generally mild to moderate. The most common sexual dysfunction
      associated with desvenlafaxine treatment was erectile dysfunction in men (7% vs
      1% with placebo) and anorgasmia in women (1% and 0%). One desvenlafaxine-treated
      patient died of a completed suicide; there were four suicide attempts (three
      desvenlafaxine, one placebo) and eight cases of suicidal ideation (five
      desvenlafaxine, three placebo) during the on-therapy period. Small but
      statistically significant changes in mean blood pressure occurred at all
      desvenlafaxine doses; clinically meaningful changes were observed in 1% of
      placebo-treated patients and 2% of desvenlafaxine-treated patients.
      Desvenlafaxine was associated with small but statistically significant mean
      changes in laboratory assessments, particularly lipid and liver enzyme
      elevations, and electrocardiograms; few cases of these changes were clinically
      relevant. CONCLUSION: Desvenlafaxine in the treatment of major depressive
      disorder exhibited a safety and tolerability profile generally consistent with
      the serotonin-norepinephrine reuptake inhibitor class. The most common adverse
      event was transient nausea. At the recommended therapeutic dose of 50 mg/day,
      discontinuation due to adverse events was similar to placebo.

PMID- 19407732
TI  - Theta burst stimulation in the treatment of incapacitating tinnitus accompanied
      by severe depression.
AB  - This case report describes the use of transcranial magnetic theta burst
      stimulation (TBS) in the treatment of incapacitating tinnitus accompanied by
      symptoms of severe depression. Tinnitus is known to be associated with
      hyperactivity and maladaptive cortical reorganization of the central auditory
      system. Combined with anxiety and depression, it can occasionally constitute a
      psychiatric emergency. Recently, it has been demonstrated that tinnitus can be
      temporarily suppressed by non-invasive transcranial magnetic stimulation. TBS is
      a newly developed technique for rapid and lasting modulation of cortical
      excitability. Herein, we present a case of a 54-year-old woman with
      incapacitating tinnitus that has significantly decreased after three cycles of 1
      week treatment with continuous TBS to the temporo-parietal auditory association
      cortex. According to the Tinnitus Questionnaire, tinnitus intensity decreased
      from 84 points before to 59 points after treatment. Hamilton Rating Scale for
      Depression score dropped from 44 to 23 points. TBS showed to be efficient, well
      tolerated, and practical in the management of distressing tinnitus accompanied by
      symptoms of severe depression.

PMID- 19407731
TI  - Aripiprazole augmentation in major depressive disorder: a double-blind, placebo
      controlled study in patients with inadequate response to antidepressants.
AB  - INTRODUCTION: Effective management of major depressive disorder (MDD) continues
      to be a challenging task for psychiatrists and primary care physicians. This
      trial evaluated the efficacy and safety of adjunctive aripiprazole versus
      antidepressant monotherapy in patients with MDD and independently replicated the
      positive findings of two similar trials. METHODS: Patients (N=1,147) with MDD
      experiencing a major depressive episode and a history of inadequate response to
      antidepressant monotherapy were enrolled (week 0); 827 received single-blind
      adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine,
      paroxetine controlled release, sertraline, or venlafaxine extended release) for 8
      weeks to confirm inadequate response to antidepressants; 349 patients with
      inadequate response were randomized (1:1) to double-blind, adjunctive placebo
      (n=172) or adjunctive aripiprazole (n=177; 2-20 mg/day). Primary outcome was the
      mean change in Montgomery-Asberg Depression Rating Scale (MADRS) Total score from
      baseline (week 8) to endpoint (week 14). RESULTS: Clinically significant
      improvements in depressive symptoms as assessed by decreases in the MADRS Total
      score were greater with adjunctive aripiprazole (-10.1) than placebo (-6.4;
      P<.001). Remission rates were greater for adjunctive aripiprazole than for
      adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with
      adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations
      due to adverse events were low (6.2% vs 1.7%). CONCLUSION: For some patients with
      MDD who do not obtain adequate symptom relief with antidepressant monotherapy,
      adjunctive therapies can significantly improve depressive symptoms. As reported,
      adjunctive aripiprazole was associated with a two-fold higher remission rate than
      adjunctive placebo. This, and previous studies, have shown that discontinuations
      due to adverse events were low and completion rates were high, and has indicated
      that both antidepressant and aripiprazole in combination were relatively well
      tolerated and safe. This is the third consecutive clinical trial, in the absence
      of a failed trial, to demonstrate that aripiprazole augmentation to
      antidepressants is an efficacious and well-tolerated treatment for patients with
      MDD who do not respond adequately to standard antidepressant monotherapy
      (ClinicalTrials.gov study NCT00105196).

PMID- 19407733
TI  - Attenuation of apparent new-onset ocular tics with successful treatment of PTSD.
AB  - This case report describes a patient with reportedly new onset of tics, beginning
      at 21 years of age, in the context of posttraumatic stress disorder (PTSD) and
      comorbid alcohol abuse, with no known head injury. The setting is an American
      Society of Addiction Medicine intensive outpatient substance abuse rehabilitation
      program in an United States Army Medical Center. The patient is a 22-year-old
      male diagnosed with alcohol abuse and delayed PTSD who presented to the program's
      medical officer due to insomnia. We discovered he had a reportedly new ocular tic
      of appoximately 9 months duration, which he claimed developed at 21 years of age
      soon after returning from 1 year of combat duty. The patient was thoroughly
      evaluated, and we surmised the tic was a symptom of PTSD. After achieving full
      remission from alcohol, the tic persisted. However, as his PTSD symptoms
      remitted, so did his tic symptoms. At 6-month follow-up, the patient reported he
      was essentially free from PTSD symptoms, and his tic was significantly reduced.

PMID- 19407734
TI  - Prevalence and most common causes of disability among adults--United States,
      2005.
AB  - Since 1994, disability-related costs for medical care and lost productivity have
      exceeded an estimated $300 billion annually in the United States. To update
      previous reports on the prevalence and most common causes of disability among
      adults, CDC and the U.S. Census Bureau analyzed the most recent data from the
      Survey of Income and Program Participation (SIPP). This report summarizes the
      findings of that analysis, which indicated that the prevalence of disability in
      2005 (21.8%) remained unchanged from 1999 (22.0%); however, because of the aging
      of the population, particularly the large group born during 1946-1964 ("baby
      boomers"), the estimated absolute number of persons reporting a disability
      increased 7.7%, from 44.1 to 47.5 million. The three most common causes of
      disability continued to be arthritis or rheumatism (affecting an estimated 8.6
      million persons), back or spine problems (7.6 million), and heart trouble (3.0
      million). Women (24.4%) had a significantly higher prevalence of disability
      compared with men (19.1%) at all ages. For both sexes, the prevalence of
      disability doubled in successive age groups (18-44 years, 11.0%; 45-64 years,
      23.9%; and >/=65 years, 51.8%). The number of adults reporting a disability
      likely will increase, along with the need for appropriate medical and public
      health services, as more persons enter the highest risk age group (>/=65 years).
      To accommodate the expected increase in demand for disability-related medical and
      public health services, expanding the reach of effective strategies and
      interventions aimed at preventing progression to disability and improving
      disability management in the population is necessary.

PMID- 19407735
TI  - Outbreak of Shiga toxin-producing Escherichia coli O157 infection associated with
      a day camp petting zoo--Pinellas County, Florida, May-June 2007.
AB  - On June 7, 2007, the Pinellas County Health Department in central Florida was
      notified by a private physician regarding a positive laboratory result for Shiga
      toxin-producing Escherichia coli O157 (STEC O157) infection in a child aged 9
      years. Initial interviews revealed the child had attended a week-long session at
      a day camp and had come into contact with animals in the camp's petting zoo. On
      June 8, an investigation was begun by the Pinellas County Health Department; the
      same day, the petting zoo was closed on the recommendation of the health
      department. This report summarizes the results of the investigation, which
      identified seven cases of STEC O157 infection: four laboratory-confirmed primary
      cases, two probable primary cases, and one laboratory-confirmed secondary case,
      all associated directly or indirectly with the petting zoo. Two children were
      hospitalized; all seven patients recovered. Petting zoo operators should adhere
      to guidelines for supervised handwashing and other prevention measures that will
      help minimize the risk in children for infection from animal contact.

PMID- 19407736
TI  - High school students who tried to quit smoking cigarettes--United States, 2007.
AB  - In the United States, cigarette use is the leading cause of preventable death,
      and most adult smokers started before the age of 18 years. Nicotine dependence
      maintains tobacco use and makes quitting difficult. Despite their relatively
      short smoking histories, many adolescents who smoke are nicotine dependent, and
      such dependence can lead to daily smoking. To examine the extent to which high
      school students had tried to quit smoking cigarettes, CDC analyzed data from the
      2007 Youth Risk Behavior Survey (YRBS), a nationally representative survey of
      students in grades 9-12 in the United States. This report describes the results
      of that analysis, which found that 60.9% of students who ever smoked cigarettes
      daily tried to quit smoking cigarettes, and 12.2% were successful. These findings
      indicate that comprehensive tobacco control programs need to continue to
      implement community-based interventions that prevent initiation and increase
      cessation and increase the use of evidence-based cessation strategies for youths.

PMID- 19407737
TI  - Update: infections with a swine-origin influenza A (H1N1) virus--United States
      and other countries, April 28, 2009.
AB  - Since April 21, 2009, CDC has reported cases of respiratory infection with a
      swine-origin influenza A (H1N1) virus (S-OIV) transmitted through human-to-human
      contact. This report updates cases identified in U.S. states and highlights
      certain control measures taken by CDC. As of April 28, the total number of
      confirmed cases of S-OIV infection in the United States had increased to 64, with
      cases in California (10 cases), Kansas (two), New York (45), Ohio (one), and
      Texas (six). CDC and state and local health departments are investigating all
      reported U.S. cases to ascertain the clinical features and epidemiologic
      characteristics. On April 27, CDC distributed an updated case definition for
      infection with S-OIV.

PMID- 19407738
TI  - Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April
      2009.
AB  - Since April 21, 2009, CDC has reported cases of respiratory infection with a
      swine-origin influenza A (H1N1) virus (S-OIV) that is being spread via human-to
      human transmission. As of April 28, the total number of confirmed S-OIV cases in
      the United States was 64; these cases occurred in California (10 cases), Kansas
      (two), New York (45), Ohio (one), and Texas (six). The viruses contain a unique
      combination of gene segments that had not been reported previously among swine or
      human influenza viruses in the United States or elsewhere. Viruses from 13 (20%)
      of 64 patients have been tested for resistance to antiviral medications. To date,
      all tested viruses are resistant to amantadine and rimantadine but are
      susceptible to oseltamivir and zanamivir. The purpose of this report is to
      provide detailed information on the drug susceptibility of the newly detected S
      OIVs, which will aid in making recommendations for treatment and prophylaxis for
      swine influenza A (H1N1) infection. These data also will contribute to antiviral
      resistance monitoring and diagnostic test development.

PMID- 19407739
TI  - Update: swine influenza A (H1N1) infections--California and Texas, April 2009.
AB  - On April 21, 2009, CDC reported that two recent cases of febrile respiratory
      illness in children in southern California had been caused by infection with
      genetically similar swine influenza A (H1N1) viruses. The viruses contained a
      unique combination of gene segments that had not been reported previously among
      swine or human influenza viruses in the United States or elsewhere. Neither child
      had known contact with pigs, resulting in concern that human-to-human
      transmission might have occurred. The seasonal influenza vaccine H1N1 strain is
      thought to be unlikely to provide protection. This report updates the status of
      the ongoing investigation and provides preliminary details about six additional
      persons infected by the same strain of swine influenza A (H1N1) virus identified
      in the previous cases, as of April 24. The six additional cases were reported in
      San Diego County, California (three cases), Imperial County, California (one
      case), and Guadalupe County, Texas (two cases). CDC, the California Department of
      Public Health, and the Texas Department of Health and Human Services are
      conducting case investigations, monitoring for illness in contacts of the eight
      patients, and enhancing surveillance to determine the extent of spread of the
      virus. CDC continues to recommend that any influenza A viruses that cannot be
      subtyped be sent promptly for testing to CDC. In addition, swine influenza A
      (H1N1) viruses of the same strain as those in the U.S. patients have been
      confirmed by CDC among specimens from patients in Mexico. Clinicians should
      consider swine influenza as well as seasonal influenza virus infections in the
      differential diagnosis for patients who have febrile respiratory illness and who
      1) live in San Diego and Imperial counties, California, or Guadalupe County,
      Texas, or traveled to these counties or 2) who traveled recently to Mexico or
      were in contact with persons who had febrile respiratory illness and were in one
      of the three U.S. counties or Mexico during the 7 days preceding their illness
      onset.

PMID- 19407740
TI  - Compendium of measures to prevent disease associated with animals in public
      settings, 2009: National Association of State Public Health Veterinarians, Inc.
      (NASPHV).
AB  - Certain venues encourage or permit the public to be in contact with animals,
      resulting in millions of human-animal interactions each year. These settings
      include county or state fairs, petting zoos, animal swap meets, pet stores,
      zoologic institutions, circuses, carnivals, educational farms, livestock-birthing
      exhibits, educational exhibits at schools and child-care facilities, and wildlife
      photo opportunities. Although human-animal contact has many benefits, many human
      health problems are associated with these settings, including infectious
      diseases, exposure to rabies, and injuries. Infectious disease outbreaks reported
      during the previous decade have been caused by Escherichia coli O157:H7,
      Salmonella species, Cryptosporidium species, Coxiella burnetii, Mycobacterium
      tuberculosis, ringworm, and other pathogens. Such infections have substantial
      medical, public health, legal, and economic effects. This report provides
      recommendations for public health officials, veterinarians, animal venue staff
      members, animal exhibitors, visitors to animal venues, physicians, and others
      concerned with minimizing risks associated with animals in public settings. The
      recommendation to wash hands is the most important prevention step for reducing
      the risk for disease transmission associated with animals in public settings.
      Other critical recommendations are that venues prohibit food in animal areas,
      venues include transition areas between animal areas and nonanimal areas,
      visitors receive information about disease risk and prevention procedures, and
      animals be properly cared for and managed. These updated 2009 guidelines also
      emphasize risks associated with baby poultry, reptiles, and rodents in public
      settings, and information about aquatic animal zoonoses has been incorporated.

PMID- 19407744
TI  - Time to act.

PMID- 19407745
TI  - Authorship policies.

PMID- 19407751
TI  - Journal club. A cell biologist ponders an outstanding mystery in muscle
      formation.

PMID- 19407756
TI  - Swine flu goes global.

PMID- 19407757
TI  - California in clean-fuel drive.

PMID- 19407758
TI  - Basic researchers protest UK budget.

PMID- 19407759
TI  - Japan goes for the sun.

PMID- 19407760
TI  - Obama says more money.

PMID- 19407761
TI  - Funding cut for US nuclear waste dump.

PMID- 19407769
TI  - Climate crunch: A burden beyond bearing.

PMID- 19407770
TI  - Climate crunch: Sucking it up.

PMID- 19407771
TI  - Climate crunch: Great white hope.

PMID- 19407772
TI  - Romanian funding cuts call for more stringent criteria.

PMID- 19407773
TI  - A lesson or two from a regional economic argument.

PMID- 19407774
TI  - Stem-cell treatments for spinal-cord injury may be worth the risk.

PMID- 19407775
TI  - Overshoot, adapt and recover.

PMID- 19407776
TI  - The worst-case scenario.

PMID- 19407786
TI  - Climate change: Too much of a bad thing.

PMID- 19407787
TI  - Cell biology: Another way to get rid of fat.

PMID- 19407788
TI  - X-ray astronomy: When appearances are deceptive.

PMID- 19407790
TI  - Ecology: Speciation affects ecosystems.

PMID- 19407789
TI  - Miniature devices: Voyage of the microrobots.

PMID- 19407791
TI  - Solid-state physics: Lost magnetic moments.

PMID- 19407792
TI  - Neuroscience: A social hub for worms.

PMID- 19407795
TI  - Discrete sources as the origin of the Galactic X-ray ridge emission.
AB  - An unresolved X-ray glow (at energies above a few kiloelectronvolts) was
      discovered about 25 years ago and found to be coincident with the Galactic disk
      the Galactic ridge X-ray emission. This emission has a spectrum characteristic of
      a approximately 10(8) K optically thin thermal plasma, with a prominent iron
      emission line at 6.7 keV. The gravitational well of the Galactic disk, however,
      is far too shallow to confine such a hot interstellar medium; instead, it would
      flow away at a velocity of a few thousand kilometres per second, exceeding the
      speed of sound in the gas. To replenish the energy losses requires a source of
      10(43) erg s(-1), exceeding by orders of magnitude all plausible energy sources
      in the Milky Way. An alternative is that the hot plasma is bound to a multitude
      of faint sources, which is supported by the recently observed similarities in the
      X-ray and near-infrared surface brightness distributions (the latter traces the
      Galactic stellar distribution). Here we report that at energies of approximately
      6-7 keV, more than 80 per cent of the seemingly diffuse X-ray emission is
      resolved into discrete sources, probably accreting white dwarfs and coronally
      active stars.

PMID- 19407794
TI  - Cytoplasmic functions of the tumour suppressor p53.
AB  - The principal tumour-suppressor protein, p53, accumulates in cells in response to
      DNA damage, oncogene activation and other stresses. It acts as a nuclear
      transcription factor that transactivates genes involved in apoptosis, cell cycle
      regulation and numerous other processes. An emerging area of research unravels
      additional activities of p53 in the cytoplasm, where it triggers apoptosis and
      inhibits autophagy. These previously unknown functions contribute to the mission
      of p53 as a tumour suppressor.

PMID- 19407796
TI  - Serial time-encoded amplified imaging for real-time observation of fast dynamic
      phenomena.
AB  - Ultrafast real-time optical imaging is an indispensable tool for studying
      dynamical events such as shock waves, chemical dynamics in living cells, neural
      activity, laser surgery and microfluidics. However, conventional CCDs (charge
      coupled devices) and their complementary metal-oxide-semiconductor (CMOS)
      counterparts are incapable of capturing fast dynamical processes with high
      sensitivity and resolution. This is due in part to a technological limitation-it
      takes time to read out the data from sensor arrays. Also, there is the
      fundamental compromise between sensitivity and frame rate; at high frame rates,
      fewer photons are collected during each frame-a problem that affects nearly all
      optical imaging systems. Here we report an imaging method that overcomes these
      limitations and offers frame rates that are at least 1,000 times faster than
      those of conventional CCDs. Our technique maps a two-dimensional (2D) image into
      a serial time-domain data stream and simultaneously amplifies the image in the
      optical domain. We capture an entire 2D image using a single-pixel photodetector
      and achieve a net image amplification of 25 dB (a factor of 316). This overcomes
      the compromise between sensitivity and frame rate without resorting to cooling
      and high-intensity illumination. As a proof of concept, we perform continuous
      real-time imaging at a frame speed of 163 ns (a frame rate of 6.1 MHz) and a
      shutter speed of 440 ps. We also demonstrate real-time imaging of microfluidic
      flow and phase-explosion effects that occur during laser ablation.

PMID- 19407797
TI  - The Kondo effect in ferromagnetic atomic contacts.
AB  - Iron, cobalt and nickel are archetypal ferromagnetic metals. In bulk, electronic
      conduction in these materials takes place mainly through the s and p electrons,
      whereas the magnetic moments are mostly in the narrow d-electron bands, where
      they tend to align. This general picture may change at the nanoscale because
      electrons at the surfaces of materials experience interactions that differ from
      those in the bulk. Here we show direct evidence for such changes: electronic
      transport in atomic-scale contacts of pure ferromagnets (iron, cobalt and
      nickel), despite their strong bulk ferromagnetism, unexpectedly reveal Kondo
      physics, that is, the screening of local magnetic moments by the conduction
      electrons below a characteristic temperature. The Kondo effect creates a sharp
      resonance at the Fermi energy, affecting the electrical properties of the system;
      this appears as a Fano-Kondo resonance in the conductance characteristics as
      observed in other artificial nanostructures. The study of hundreds of contacts
      shows material-dependent log-normal distributions of the resonance width that
      arise naturally from Kondo theory. These resonances broaden and disappear with
      increasing temperature, also as in standard Kondo systems. Our observations,
      supported by calculations, imply that coordination changes can significantly
      modify magnetism at the nanoscale. Therefore, in addition to standard
      micromagnetic physics, strong electronic correlations along with atomic-scale
      geometry need to be considered when investigating the magnetic properties of
      magnetic nanostructures.

PMID- 19407798
TI  - The ITQ-37 mesoporous chiral zeolite.
AB  - The synthesis of crystalline molecular sieves with pore dimensions that fill the
      gap between microporous and mesoporous materials is a matter of fundamental and
      industrial interest. The preparation of zeolitic materials with extralarge pores
      and chiral frameworks would permit many new applications. Two important steps in
      this direction include the synthesis of ITQ-33, a stable zeolite with 18 x 10 x
      10 ring windows, and the synthesis of SU-32, which has an intrinsically chiral
      zeolite structure and where each crystal exhibits only one handedness. Here we
      present a germanosilicate zeolite (ITQ-37) with extralarge 30-ring windows. Its
      structure was determined by combining selected area electron diffraction (SAED)
      and powder X-ray diffraction (PXRD) in a charge-flipping algorithm. The framework
      follows the SrSi(2) (srs) minimal net and forms two unique cavities, each of
      which is connected to three other cavities to form a gyroidal channel system.
      These cavities comprise the enantiomorphous srs net of the framework. ITQ-37 is
      the first chiral zeolite with one single gyroidal channel. It has the lowest
      framework density (10.3 T atoms per 1,000 A(3)) of all existing 4-coordinated
      crystalline oxide frameworks, and the pore volume of the corresponding silica
      polymorph would be 0.38 cm(3) g(-1).

PMID- 19407799
TI  - Greenhouse-gas emission targets for limiting global warming to 2 degrees C.
AB  - More than 100 countries have adopted a global warming limit of 2 degrees C or
      below (relative to pre-industrial levels) as a guiding principle for mitigation
      efforts to reduce climate change risks, impacts and damages. However, the
      greenhouse gas (GHG) emissions corresponding to a specified maximum warming are
      poorly known owing to uncertainties in the carbon cycle and the climate response.
      Here we provide a comprehensive probabilistic analysis aimed at quantifying GHG
      emission budgets for the 2000-50 period that would limit warming throughout the
      twenty-first century to below 2 degrees C, based on a combination of published
      distributions of climate system properties and observational constraints. We show
      that, for the chosen class of emission scenarios, both cumulative emissions up to
      2050 and emission levels in 2050 are robust indicators of the probability that
      twenty-first century warming will not exceed 2 degrees C relative to pre
      industrial temperatures. Limiting cumulative CO(2) emissions over 2000-50 to
      1,000 Gt CO(2) yields a 25% probability of warming exceeding 2 degrees C-and a
      limit of 1,440 Gt CO(2) yields a 50% probability-given a representative estimate
      of the distribution of climate system properties. As known 2000-06 CO(2)
      emissions were approximately 234 Gt CO(2), less than half the proven economically
      recoverable oil, gas and coal reserves can still be emitted up to 2050 to achieve
      such a goal. Recent G8 Communiques envisage halved global GHG emissions by 2050,
      for which we estimate a 12-45% probability of exceeding 2 degrees C-assuming 1990
      as emission base year and a range of published climate sensitivity distributions.
      Emissions levels in 2020 are a less robust indicator, but for the scenarios
      considered, the probability of exceeding 2 degrees C rises to 53-87% if global
      GHG emissions are still more than 25% above 2000 levels in 2020.

PMID- 19407800
TI  - Warming caused by cumulative carbon emissions towards the trillionth tonne.
AB  - Global efforts to mitigate climate change are guided by projections of future
      temperatures. But the eventual equilibrium global mean temperature associated
      with a given stabilization level of atmospheric greenhouse gas concentrations
      remains uncertain, complicating the setting of stabilization targets to avoid
      potentially dangerous levels of global warming. Similar problems apply to the
      carbon cycle: observations currently provide only a weak constraint on the
      response to future emissions. Here we use ensemble simulations of simple climate
      carbon-cycle models constrained by observations and projections from more
      comprehensive models to simulate the temperature response to a broad range of
      carbon dioxide emission pathways. We find that the peak warming caused by a given
      cumulative carbon dioxide emission is better constrained than the warming
      response to a stabilization scenario. Furthermore, the relationship between
      cumulative emissions and peak warming is remarkably insensitive to the emission
      pathway (timing of emissions or peak emission rate). Hence policy targets based
      on limiting cumulative emissions of carbon dioxide are likely to be more robust
      to scientific uncertainty than emission-rate or concentration targets. Total
      anthropogenic emissions of one trillion tonnes of carbon (3.67 trillion tonnes of
      CO(2)), about half of which has already been emitted since industrialization
      began, results in a most likely peak carbon-dioxide-induced warming of 2 degrees
      C above pre-industrial temperatures, with a 5-95% confidence interval of 1.3-3.9
      degrees C.

PMID- 19407801
TI  - Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic
      inflammation.
AB  - Gene silencing by double-stranded RNA, denoted RNA interference, represents a new
      paradigm for rational drug design. However, the transformative therapeutic
      potential of short interfering RNA (siRNA) has been stymied by a key obstacle
      safe delivery to specified target cells in vivo. Macrophages are particularly
      attractive targets for RNA interference therapy because they promote pathogenic
      inflammatory responses in diseases such as rheumatoid arthritis, atherosclerosis,
      inflammatory bowel disease and diabetes. Here we report the engineering of
      beta1,3-D-glucan-encapsulated siRNA particles (GeRPs) as efficient oral delivery
      vehicles that potently silence genes in mouse macrophages in vitro and in vivo.
      Oral gavage of mice with GeRPs containing as little as 20 microg kg(-1) siRNA
      directed against tumour necrosis factor alpha (Tnf-alpha) depleted its messenger
      RNA in macrophages recovered from the peritoneum, spleen, liver and lung, and
      lowered serum Tnf-alpha levels. Screening with GeRPs for inflammation genes
      revealed that the mitogen-activated protein kinase kinase kinase kinase 4
      (Map4k4) is a previously unknown mediator of cytokine expression. Importantly,
      silencing Map4k4 in macrophages in vivo protected mice from lipopolysaccharide
      induced lethality by inhibiting Tnf-alpha and interleukin-1beta production. This
      technology defines a new strategy for oral delivery of siRNA to attenuate
      inflammatory responses in human disease.

PMID- 19407803
TI  - Center effect on ankle-brachial index measurement when using the reference method
      (Doppler and manometer): results from a large cohort study.
AB  - BACKGROUND: The ankle-brachial index (ABI) is a simple and noninvasive tool used
      to detect peripheral arterial disease (PAD). We aimed to assess, in a French
      multicenter cohort, the center effect associated with arterial pressure (AP) and
      ABI measurements using the reference method and using a semiautomatic device.
      METHODS: This study included baseline and 9-year follow-up data from 3,664
      volunteers of 10 health examination centers of the DESIR (Data from an
      Epidemiological Study on the Insulin Resistance) syndrome French cohort. Ankle
      and brachial AP were measured at inclusion by the reference method (a mercury
      sphygmomanometer coupled with a Doppler probe for ankle measurements) and at 9
      years by a semiautomatic device (Omron HEM-705CP). The center effect was assessed
      by the intraclass correlation coefficient (ICC), ratio of the between-center
      variance to the total variance of the measurement. RESULTS: At inclusion, the
      sample mean age was 47.5 (s.d. 9.9) years; 49.3% were men. Although ICCs were
      smaller than 0.05 for brachial AP measurements, they were close to 0.18 and 0.20
      for ankle systolic AP (SAP) and ABI measurements, respectively, when the
      reference method was used. No center effect for measures other than ankle SAP was
      detected. With the semiautomatic device method, all ICCs, including those for
      ankle SAP and ABI measurements, were between 0.005 and 0.04. CONCLUSIONS: We
      found an important center effect on ABI measured with a sphygmomanometer and a
      Doppler probe but not a semiautomatic device. A center effect should be taken
      into account when planning any multicenter study on ABI measurement.

PMID- 19407804
TI  - Genetic and pharmacogenetic associations between NOS3 polymorphisms, blood
      pressure, and cardiovascular events in hypertension.
AB  - BACKGROUND: Polymorphisms in the endothelial nitric oxide synthase (NOS3) gene
      increase susceptibility to hypertension and cardiovascular disease. We examined
      genetic and pharmacogenetic associations between NOS3 polymorphisms, blood
      pressure (BP) control, and cardiovascular events in elderly, hypertensive
      coronary artery disease (CAD) patients. METHODS: Patients with CAD were randomly
      assigned to either verapamil SR- or atenolol-based antihypertensive treatment and
      followed for cardiovascular events. Cases (all-cause death, nonfatal myocardial
      infarction (MI), or nonfatal stroke) and an age-, sex-, race/ethnicity-matched
      control population were genotyped for the -786T>C and Glu298>Asp polymorphisms in
      NOS3. On-treatment BP and BP control were compared across genotype groups.
      Logistic regression was performed to estimate odds ratios (ORs) for the -786T>C
      and Glu298>Asp polymorphisms in the combined population and in randomized
      treatment groups. RESULTS: Genotype data were available for 256 cases and 769
      controls. Among controls, mean on-treatment BP differed according to -786T>C
      genotype (T/T 137/78 mm Hg, T/C 133/76 mm Hg, C/C 133/75 mm Hg; P = 0.0007 for
      systolic, P = 0.09 for diastolic) which corresponded to differing rates of BP
      control (T/T 63%, T/C 72%, C/C 88%; P = 0.002). Neither polymorphisms was
      associated with case status, with or without regard to assigned treatment.
      CONCLUSIONS: The -786T>C, but not the Glu298>Asp variant of NOS3, may correlate
      with BP but do not appear to be associated with incident cardiovascular events in
      patients with established cardiovascular disease. The antihypertensive treatment
      approach did not appear to alter the genetic contribution to either BP control or
      cardiovascular events.

PMID- 19407806
TI  - Association between wall shear stress and carotid atherosclerosis in patients
      with never treated essential hypertension.
AB  - BACKGROUND: Wall shear stress (WSS) has been shown to be a critical determinant
      of vessel diameter implicated in vascular remodeling and atherogenesis. Carotid
      intima-media thickness (IMT), resistive index (RI), and pulsatility index (PI)
      have been used as relevant indictors for carotid atherosclerosis. The study aimed
      to investigate the relationship between hemodynamic parameters in the common
      carotid artery (CCA) and the severity of carotid atherosclerosis in untreated
      hypertensive patients. METHODS: Duplex ultrasound was performed in 64 untreated
      hypertensive patients and 16 age-matched normotensive control subjects.
      Morphologic and hemodynamic parameters of CCA, including peak and mean WSS, RI,
      PI, and IMT were calculated after measuring internal diameter (ID) and flow
      velocity of CCA. RESULTS: Subjects with hypertension had lower peak and mean WSS
      than did normotensive control subjects (P < 0.05). Both carotid RI and PI were
      found to correlate inversely with mean WSS in hypertensive subjects. There was no
      correlation between carotid IMT and WSS. Stepwise multiple regression analysis
      for carotid RI and PI after adjustment for age, carotid IMT, and high sensitivity
      C-reactive protein (hsCRP) showed that mean WSS was an independent determinant of
      RI and PI. CONCLUSIONS: High carotid atherosclerotic indexes as expressed by both
      RI and PI are associated with low WSS in CCA. These findings indicate that local
      shear stress is associated with altered vascular pulsatility and resistance.
      Consequent alteration in local vascular dynamics could be an underlying mechanism
      for the progression of atherosclerosis.

PMID- 19407805
TI  - Ambulatory blood pressure control with bedtime aspirin administration in subjects
      with prehypertension.
AB  - BACKGROUND: Aspirin has been found to prevent angiotensin II-induced hypertension
      and to induce nitric oxide (NO) release from vascular endothelium. Low-dose
      aspirin has also been shown to reduce blood pressure (BP) when administered at
      bedtime, as opposed to upon awakening, in untreated hypertensive patients and
      high-risk pregnant women. Accordingly, we investigated the effects on ambulatory
      BP of aspirin administered at different times of the day in prehypertension.
      METHODS: We studied 244 subjects with prehypertension, 43.0 +/- 13.0 years of
      age, randomly divided in three groups: nonpharmacological hygienic-dietary
      recommendations; the same recommendations and aspirin (100 mg/day) on awakening;
      or the same recommendations and aspirin at bedtime. BP was measured for 48
      consecutive hours before and after 3 months of intervention. RESULTS: Ambulatory
      BP was unchanged in subjects randomized to either nonpharmacological intervention
      or aspirin on awakening. A significant ambulatory BP reduction was, however,
      observed in the subjects who received aspirin at bedtime (decrease of 6/3 mm Hg
      in the 24-h mean of systolic (SBP)/diastolic BP (DBP), respectively; P < 0.001),
      without changes in heart rate (HR) from baseline. BP was homogeneously controlled
      along the 24 h after bedtime aspirin administration (6/4 mm Hg reduction in
      activity mean of SBP/DBP; 6/3 mm Hg reduction in sleep-time mean, respectively).
      CONCLUSIONS: This prospective trial documents a significant effect on BP of low
      dose aspirin only when ingested at bedtime by prehypertensive subjects. The timed
      administration of low-dose aspirin could thus provide a valuable and cost
      effective approach for BP control in subjects at elevated risk of developing
      hypertension.

PMID- 19407807
TI  - Psychosocial stress and 13-year BMI change among blacks: the Pitt County Study.
AB  - Adverse psychosocial exposures may partially drive the high rates of obesity
      among blacks. The objective of this study was to prospectively examine the
      relationship between perceived psychosocial stress and percent change in BMI
      among adult black men and women. We used data from 756 women and 416 men who were
      participants in the Pitt County Study, a community-based, prospective cohort
      study of blacks in eastern North Carolina. Participants were aged 25-50 years of
      age on entry into the study in 1988 and follow-up was obtained in 2001. Using
      multivariable linear regression, we calculated the adjusted mean percentage
      change in BMI over the follow-up period for each tertile of baseline measures of
      the Perceived Stress Scale (low, medium, and high), adjusted for potential
      confounders. For black women, higher levels of psychosocial stress at baseline
      predicted higher adjusted percentage increase in BMI over the 13-year follow-up:
      low stress 12.0% (95% CI 9.6-14.4), medium stress 16.3% (95% CI 13.7-18.9), and
      high stress 15.5% (95% CI 13.1-17.8). For black men, perceived stress was not
      associated with percent BMI change. These data suggest that interventions
      targeting obesity in black women should consider the potential impact of
      emotional stress on weight change.

PMID- 19407808
TI  - Fat and water 1H MRI to investigate effects of leptin in obese mice.
AB  - Leptin is known to be associated with regulation of body weight and fat content.
      The effects of exogenous leptin on abdominal visceral (VS) and subcutaneous (SC)
      fat volume and hepatic fat-to-water ratio in leptin-deficient obese mice were
      investigated by (1)H magnetic resonance imaging (MRI). Chemical shift-selected
      fat and water (1)H MRI of control and leptin-treated mice were obtained 1 day
      before treatment and after 7 days of treatment (0.3 mg/kg/day). Hepatic fat-to
      water ratio and VS fat volume decreased significantly with treatment, whereas SC
      fat volume did not change. Noninvasive measurement of fat and water content in
      different body regions using MRI should prove useful for evaluating new drugs for
      the treatment of obesity and other metabolic disorders.

PMID- 19407809
TI  - Genetic and environmental contributions to phenotypic components of metabolic
      syndrome: a population-based twin study.
AB  - The increasing prevalence of metabolic syndrome (MS) poses a serious public
      health problem worldwide. Effective prevention and intervention require improved
      understanding of the factors that contribute to MS. We analyzed data on a large
      twin cohort to estimate genetic and environmental contributions to MS and to
      major MS components and their intercorrelations: waist circumference (WC),
      systolic (SBP) and diastolic blood pressure (DBP), fasting plasma glucose (FPG),
      triglycerides (TGs), and high-density lipoprotein-cholesterol (HDL-C). We applied
      structural equation modeling to determine genetic and environmental structure of
      MS and its major components, using 1,617 adult female twin pairs recruited from
      rural China. The heritability estimate for MS was 0.42 (95% confidence interval
      (CI): 0.00-0.83) in this sample with low MS prevalence (4.4%). For MS components,
      heritability estimates were statistically significant and ranged from 0.13 to
      0.64 highest for WC, followed by TG, SBP, DBP, HDL-C, and FPG. HDL-C was mainly
      influenced by common environmental factors (0.62, 95% CI: 0.58-0.62), whereas the
      other five MS components were largely influenced by unique environmental factors
      (0.32-0.44). Bivariate Cholesky decomposition analysis indicated that the
      clinical clustering of MS components may be explained by shared genetic and/or
      environmental factors. Our study underscores the importance of examining MS
      components as intercorrelated traits, and to carefully consider environmental and
      genetic factors in studying MS etiology.

PMID- 19407810
TI  - Randomized trial of a behavioral weight loss intervention for low-income women:
      the Weight Wise Program.
AB  - Low-income women in the United States have the highest rates of obesity, yet they
      are seldom included in weight loss trials. To address this research gap,
      components of two evidence-based weight loss interventions were adapted to create
      a 16-week intervention for low-income women (Weight Wise Program), which was
      evaluated in a randomized trial with the primary outcome of weight loss at 5
      month follow-up. Participants were low-income women (40-64 years) with a BMI of
      25-45. Of 143 participants, 72 were randomized to the Weight Wise Program (WWP)
      and 71 to the Control Group (CG). Five-month follow-up data were obtained from 64
      (89%) WWP and 62 (87%) CG participants. With baseline values carried forward for
      missing data, WWP participants had a weight change of -3.7 kg compared to 0.7 kg
      in the CG (4.4 kg difference, 95% confidence interval (CI), 3.2-5.5, P<0.001).
      For systolic blood pressure (SBP), change in the WWP was -6.5 mm Hg compared to 
      0.4 mm Hg among controls (6.2 mm Hg difference, 95% CI, 1.7-10.6, P=0.007); for
      diastolic BP (DBP), changes were -4.1 mm Hg for WWP compared to -1.3 mm Hg for
      controls (2.8 mm Hg difference, 95% CI, 0.0-5.5, P=0.05). Of the 72 WWP
      participants, 64, 47, and 19% lost at least 3, 5, and 7% of their initial body
      weight, respectively. In conclusion, the WWP was associated with statistically
      significant and clinically important short-term weight loss.

PMID- 19407811
TI  - BubR1 acetylation at prometaphase is required for modulating APC/C activity and
      timing of mitosis.
AB  - Regulation of BubR1 is central to the control of APC/C activity. We have found
      that BubR1 forms a complex with PCAF and is acetylated at lysine 250. Using mass
      spectrometry and acetylated BubR1-specific antibodies, we have confirmed that
      BubR1 acetylation occurs at prometaphase. Importantly, BubR1 acetylation was
      required for checkpoint function, through the inhibition of ubiquitin-dependent
      BubR1 degradation. BubR1 degradation began before the onset of anaphase. It was
      noted that the pre-anaphase degradation was regulated by BubR1 acetylation.
      Degradation of an acetylation-mimetic form, BubR1-K250Q, was inhibited and
      chromosome segregation in cells expressing BubR1-K250Q was markedly delayed. By
      contrast, the acetylation-deficient mutant, BubR1-K250R, was unstable, and
      mitosis was accelerated in BubR1-K250R-expressing cells. Furthermore, we found
      that APC/C-Cdc20 was responsible for BubR1 degradation during mitosis. On the
      basis of our collective results, we propose that the acetylation status of BubR1
      is a molecular switch that converts BubR1 from an inhibitor to a substrate of the
      APC/C complex, thus providing an efficient way to modulate APC/C activity and
      mitotic timing.

PMID- 19407812
TI  - Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and
      H3K56Ac in human cells.
AB  - Recognition and repair of damaged DNA occurs within the context of chromatin. The
      key protein components of chromatin are histones, whose post-translational
      modifications control diverse chromatin functions. Here, we report our findings
      from a large-scale screen for DNA-damage-responsive histone modifications in
      human cells. We have identified specific phosphorylations and acetylations on
      histone H3 that decrease in response to DNA damage. Significantly, we find that
      DNA-damage-induced changes in H3S10p, H3S28p and H3.3S31p are a consequence of
      cell-cycle re-positioning rather than DNA damage per se. In contrast, H3K9Ac and
      H3K56Ac, a mark previously uncharacterized in human cells, are rapidly and
      reversibly reduced in response to DNA damage. Finally, we show that the histone
      acetyl-transferase GCN5/KAT2A acetylates H3K56 in vitro and in vivo.
      Collectively, our data indicate that though most histone modifications do not
      change appreciably after genotoxic stress, H3K9Ac and H3K56Ac are reduced in
      response to DNA damage in human cells.

PMID- 19407813
TI  - NRH2 is a trafficking switch to regulate sortilin localization and permit
      proneurotrophin-induced cell death.
AB  - Proneurotrophins mediate neuronal apoptosis using a dual receptor complex of
      sortilin and p75(NTR). Although p75(NTR) is highly expressed on the plasma
      membrane and accessible to proneurotrophin ligands, sortilin is primarily
      localized to intracellular membranes, limiting the formation of a cell surface co
      receptor complex. Here, we show that the mammalian p75(NTR) homologue NRH2
      critically regulates the expression of sortilin on the neuronal cell surface and
      promotes p75(NTR) and sortilin receptor complex formation, rendering cells
      responsive to proneurotrophins. This is accomplished by interactions between the
      cytoplasmic domains of NRH2 and sortilin that impair lysosomal degradation of
      sortilin. In proneurotrophin-responsive neurons, acute silencing of endogenous
      NRH2 significantly reduces cell surface-expressed sortilin and abolishes
      proneurotrophin-induced neuronal death. Thus, these data suggest that NRH2 acts
      as a trafficking switch to impair lysosomal-dependant sortilin degradation and to
      redistribute sortilin to the cell surface, rendering p75(NTR)-expressing cells
      susceptible to proneurotrophin-induced death.

PMID- 19407815
TI  - Small RNA-induced differential degradation of the polycistronic mRNA iscRSUA.
AB  - Most polycistronic genes are expressed in a single transcript, in which each
      cistron produces a fixed amount of protein. In this report, we show the first
      example of differential degradation of a polycistronic gene induced by a small
      regulatory RNA (sRNA). Our data show that the iron-responsive sRNA, RyhB, binds
      to the second cistron of the polycistronic mRNA, iscRSUA, which encodes the
      necessary machinery for biosynthesis of Fe-S clusters, and promotes the cleavage
      of the downstream iscSUA transcript. This cleavage gives rise to the remaining 5'
      section of the transcript encoding IscR, a transcriptional regulator responsible
      for activation and repression of several genes depending on the cellular Fe-S
      level. Our data indicate that the iscR transcript is stable and that translation
      is active. The stability of the iscR transcript depends on a 111-nucleotide long
      non-translated RNA section located between iscR and iscS, which forms a strong
      repetitive extragenic palindromic secondary structure and may protect against
      ribonucleases degradation. This novel regulation shows how sRNAs and mRNA
      structures can work together to modulate the transcriptional response to a
      specific stress.

PMID- 19407814
TI  - XBP-1 regulates signal transduction, transcription factors and bone marrow
      colonization in B cells.
AB  - XBP-1, a transcription factor that drives the unfolded protein response (UPR), is
      activated in B cells when they differentiate to plasma cells. Here, we show that
      in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is
      induced normally on induction of differentiation, suggesting that activation of
      XBP-1 in B cells is a differentiation-dependent event, but not the result of a
      UPR caused by the abundant synthesis of secreted IgM. Without XBP-1, B cells fail
      to signal effectively through the B-cell receptor. The signalling defects lead to
      aberrant expression of the plasma cell transcription factors IRF4 and Blimp-1,
      and altered levels of activation-induced cytidine deaminase and sphingosine-1
      phosphate receptor. Using XBP-1-deficient/Blimp-1-GFP transgenic mice, we find
      that XBP-1-deficient B cells form antibody-secreting plasmablasts in response to
      initial immunization; however, these plasmablasts respond ineffectively to
      CXCL12. They fail to colonize the bone marrow and do not sustain antibody
      production. These findings define the role of XBP-1 in normal plasma cell
      development and have implications for management of B-cell malignancies.

PMID- 19407816
TI  - The picobirnavirus crystal structure provides functional insights into virion
      assembly and cell entry.
AB  - Double-stranded (ds) RNA virus particles are organized around a central
      icosahedral core capsid made of 120 identical subunits. This core capsid is
      unable to invade cells from outside, and animal dsRNA viruses have acquired
      surrounding capsid layers that are used to deliver a transcriptionally active
      core particle across the membrane during cell entry. In contrast, dsRNA viruses
      infecting primitive eukaryotes have only a simple core capsid, and as a
      consequence are transmitted only vertically. Here, we report the 3.4 A X-ray
      structure of a picobirnavirus--an animal dsRNA virus associated with diarrhoea
      and gastroenteritis in humans. The structure shows a simple core capsid with a
      distinctive icosahedral arrangement, displaying 60 two-fold symmetric dimers of a
      coat protein (CP) with a new 3D-fold. We show that, as many non-enveloped animal
      viruses, CP undergoes an autoproteolytic cleavage, releasing a post
      translationally modified peptide that remains associated with nucleic acid within
      the capsid. Our data also show that picobirnavirus particles are capable of
      disrupting biological membranes in vitro, indicating that its simple 120-subunits
      capsid has evolved animal cell invasion properties.

PMID- 19407818
TI  - Augmentation index is associated with B-type natriuretic peptide in patients with
      paroxysmal atrial fibrillation.
AB  - B-type natriuretic peptide (BNP) levels have been shown to be elevated in
      patients with paroxysmal atrial fibrillation (PAF); however, the underlying
      mechanisms have not been fully elucidated. Earlier, we reported that an increase
      in the augmentation index (AI), which is an index of wave reflection and arterial
      stiffness, is associated with PAF. In this study, we investigate the relationship
      between the BNP level and AI in patients with PAF. We enrolled 92 patients with a
      history of PAF and 90 age- and gender-matched individuals without PAF. AI was
      calculated using applanation tonometry of the radial artery when all patients
      were on sinus rhythm. Plasma BNP levels were measured simultaneously. An arterial
      stiffness parameter, the cardio-ankle vascular index (CAVI), was also evaluated.
      The increased AI in patients with PAF correlated with the elevation of the BNP
      level (r=0.47, P<0.01). When PAF patients were classified into tertiles on the
      basis of the BNP level, the left atrial volume index, left ventricular mass
      index, AI and CAVI increased, and mitral annular e' velocity (e'), as an index of
      left ventricular diastolic pressure, decreased with BNP tertiles. AI was also
      associated with e' and left ventricular mass index. Multiple regression analysis
      showed that the AI in PAF patients independently correlated with BNP levels. This
      study showed that AI was an independent correlate of the BNP level in PAF
      patients. Left ventricular diastolic dysfunction, which linked to an increase in
      arterial stiffness, may be involved in the elevated BNP level.

PMID- 19407817
TI  - H3 lysine 4 di- and tri-methylation deposited by cryptic transcription attenuates
      promoter activation.
AB  - Set1-dependent H3K4 di- and tri-methylation (H3K4me2/3) have been associated with
      active transcription. Recent data indicate that the H3K4me2/3 also plays a poorly
      characterized RNA-dependent repressive role. Here, we show that GAL1 promoter is
      attenuated by the H3K4me2/3 deposited by cryptic transcription. The H3K4me2/3
      delay the recruitment of RNA polymerase II (RNAPII) and TBP on GAL1 promoter.
      Inactivation of RNA decay components revealed the existence of the RNAPII
      dependent unstable RNAs, initiating upstream of GAL1 (GAL1ucut). GAL1ucut RNAs
      are synthesized in glucose and require the Reb1 transcription factor. Consistent
      with a regulatory function of the cryptic transcription, Reb1 depletion leads to
      a decrease of H3K4me3 on GAL10-GAL1 locus in glucose and to an acceleration of
      GAL1 induction. A candidate approach shows that the RPD3 histone deacetylase
      attenuates GAL1 induction and is tethered at the GAL10-GAL1 locus by H3K4me2/3
      upon repression. Strikingly, Set1-dependent Rpd3 recruitment represses also the
      usage of a hidden promoter within SUC2, suggesting a general function for
      H3K4me2/3 in promoter fidelity. Our data support a model wherein certain
      promoters are embedded in a repressive chromatin controlled by cryptic
      transcription.

PMID- 19407819
TI  - Functional alterations of mesenteric small resistance arteries in Milan
      hypertensive and normotensive rats.
AB  - The Milan hypertensive rat strain (MHS) is a genetic strain in which
      cardiovascular phenotypes seem to be dependent, at least in part, on adducin gene
      polymorphisms. The aim of our study was to evaluate the structure, contractile
      responses and endothelium-dependent vasodilation in mesenteric small resistance
      arteries in 12-week-old MHS, (n=7), age-matched Milan normotensive rats (MNS,
      n=7) and congenic strains in which the DNA segments carrying the alpha-adducin
      locus from the MHS have been introgressed into the MNS (MNA, n=7). Systolic blood
      pressure (tail cuff) and left ventricular weight to body weight were measured.
      Mesenteric small arteries were dissected and mounted on a micromyograph; the
      media:lumen ratio was then calculated. Concentration-response curves to
      acetylcholine and to norepinephrine (NE) were created. Systolic blood pressure
      was significantly increased in the MHS and MNA strains compared with the MNS. No
      significant difference in mesenteric small resistance artery structure was
      observed among the groups; however, a slightly more elevated media:lumen ratio
      was observed in MNA compared with the MNS. In contrast, left ventricular weight
      to body weight was significantly increased and ACH-induced dilatation was
      significantly impaired in the MHS and in MNA compared with MNS. The concentration
      response curve to NE in the MHS showed significantly reduced sensitivity to NE;
      however, maximum contraction was increased in the MHS vs. the other groups. The
      MHS presents cardiac (but not vascular) remodeling, endothelial dysfunction and a
      peculiar contractile response to NE, compared with the other groups. The systolic
      blood pressure increase and trend to vascular remodeling in MNA support the
      pathogenic role of alpha-adducin.

PMID- 19407821
TI  - Blood pressure reactivity to emotional stress is reduced in AT1A-receptor
      knockout mice on normal, but not high salt intake.
AB  - Pharmacological evidence suggests that angiotensin II type 1 (AT(1)) receptors
      are involved in the regulation of cardiovascular response to emotional stress and
      reinforcing effect of dietary salt on this response. In this study, we examined
      the effect of genetic deletion of AT(1A) receptors on the cardiovascular effects
      of stress and salt in mice. AT(1A) receptor knockout (AT(1A)(-/-)) and wild-type
      (AT(1A)(+/+)) mice were implanted with telemetry devices and placed on a normal
      (0.4%) or high (3.1%) salt diet (HSD). Resting blood pressure (BP) in AT(1A)(-/-)
      mice (84+/-3 mm Hg) was lower than in AT(1A)(+/+) mice (107+/-2 mm Hg). Negative
      emotional (restraint) stress increased BP by 33+/-3 mm Hg in AT(1A)(+/+) mice.
      This response was attenuated by 40% in AT(1A)(-/-) mice (18+/-3 mm Hg).
      Conversely, the BP increase caused by food presentation and feeding was similar
      in AT(1A)(-/-) (25+/-3 mm Hg) and AT(1A)(+/+) mice (26+/-3 mm Hg). HSD increased
      resting BP by 14+/-4 mm Hg in AT(1A)(-/-) mice without affecting it significantly
      in AT(1A)(+/+) mice. Under these conditions, the pressor response to restraint
      stress in AT(1A)(-/-) mice (30+/-3 mm Hg) was no longer different from that in
      wild-type animals (28+/-3 mm Hg). The BP response to feeding was not altered by
      HSD in either AT(1A)(-/-) or AT(1A)(+/+) mice (25+/-2 and 27+/-3 mm Hg,
      respectively). These results indicate that AT(1A) receptor deficiency leads to a
      reduction in BP reactivity to negative emotional stress, but not feeding. HSD can
      selectively reinforce the cardiovascular response to negative stress in AT(1A)(-/
      ) mice. However, there is little interaction between AT(1A) receptors, excess
      dietary sodium and feeding-induced cardiovascular arousal.

PMID- 19407822
TI  - Cytokine gene polymorphisms in preeclampsia and eclampsia.
AB  - The clinical spectrum of preeclampsia (PE) ranges from mild hypertension to
      severe vasospasm associated with convulsions and multiple organ damage. The
      biological factors that determine the progression of PE to eclampsia (E) are
      unknown. Endothelial cell activation seems related to an impaired maternal immune
      response. The production of cytokines, IL-10 and TGF-beta1, is apparently
      suppressed, and altered IL-2/IL-10 and TNF-alpha/IL-10 ratios have been reported
      in preeclamptic cases. The relationship between PE and cytokine gene polymorphism
      has been studied, but there are few studies that include eclamptic patients. This
      study aimed at investigating whether polymorphisms in genes, TNF-alpha promoter (
      308 G>A), IL6 promoter (-174 G>C), IFN-gamma intron 1 (+874 A>T), IL10 promoters
      (-1082 A>G), (-819 C>T) and (-592 C>A) and TGF-beta1 codon 10 (+869 T>C) and
      codon 25 (+915 G>C) are associated with E and/or PE. Genotyping was carried out
      in 266 Mulatto women from the northeastern region of Brazil who were referred to
      a single maternity hospital: 92 with PE, 73 with E and 101 normotensive controls.
      The chi(2) or Fisher's exact tests were used to compare genotype frequencies.
      Among the six single-nucleotide polymorphisms (SNPs) studied, we found no
      difference in genotype frequencies between the groups. There was a higher
      frequency of IFN-gamma (+874 A) in eclamptic patients in comparison with that in
      controls. (70.3 vs. 57.8%, respectively; P=0.02). There were no other significant
      differences in allelic frequencies between eclamptic, preeclamptic and control
      groups We found no independent association between any single SNP and PE or E
      risk in this population of Mulatto women from the northeastern region of Brazil.

PMID- 19407823
TI  - Predictors of aortic complicated lesions in stroke patients.
AB  - Aortic complicated lesions (ACLs) should be associated with cerebral infarction.
      Our aim was to develop a simple clinical scale (ACL scale) to predict the
      presence of ACL. Consecutive stroke patients undergoing transesophageal
      echocardiogram (TEE) examination were prospectively enrolled. We defined ACL as
      the presence of >4 mm wall thickness, ulceration or mobile plaque in aortic arch.
      We also examined carotid intima-media thickness (IMT), ankle-brachial index (ABI)
      and brachial-ankle pulse-wave velocity (baPWV). We compared the clinical
      characteristics of patients with ACL (ACL group) and without ACL (non-ACL group),
      and devised a new ACL scale to predict the presence of ACL. In all, 165 patients
      (male 108, age 66.9 years) were enrolled and of these, 38% had ACL. The patients
      of the ACL group were older than those of the non-ACL group (73.0+/-10.2 vs.
      63.1+/-13.6 years, P=0.001). Peripheral artery disease (PAD) was more frequent in
      the ACL group (18 vs. 4%, P=0.004). IMT was thicker in ACL group than in the non
      ACL group (1.29+/-0.74 vs. 1.11+/-0.79 mm, P=0.002), and baPWV was higher in the
      ACL group (2164.2+/-643.2 vs. 1833.7+/-492.9 cm s(-1), P=0.001). We used three
      variables for determining the ACL scale score; (1) age >70, (2) presence of PAD
      and (3) smoking. The frequencies of ACL associated with ACL scale scores were as
      follows: 6% of patients with ACL scale score 0, 40% with score 1, 58% with score
      2 and 100% with score 3. The ACL scale can predict the presence of aortic
      complicated lesions.

PMID- 19407824
TI  - Blockade of angiotensin II type-1 receptor increases salt sensitivity in Sprague
      Dawley rats.
AB  - This study determined the role of angiotensin II type-1 (AT1) receptor in the
      salt sensitivity of blood pressure. The mean arterial blood pressure (MAP) of
      Sprague-Dawley rats was monitored by radio telemetry and, after baseline
      measurements, rats were treated either with (1) vehicle, (2) AT1 receptor blocker
      (ARB) olmesartan (OLM, 100 nmol kg(-1) h(-1), subcutaneously), (3) OLM with
      hydrochlorothiazide (HCTZ, 40 mg kg(-1) day(-1), orally), (4) angiotensin II
      (AngII, 100 ng kg(-1) min(-1), subcutaneously) or with (5) AngII with OLM. Rats
      were fed a 0.5% salt diet during the baseline and first 7 days of treatment
      period, and the diet was then switched to one containing 8% salt for another 7
      days. Urinary samples were collected in a metabolic cage at the end of each
      period. MAP of the vehicle group did not change throughout the study. In AngII
      infused rats, BP increased only when rats were fed an 8% salt diet. OLM and OLM
      with AngII significantly reduced MAP when rats were on a 0.5% salt diet, but not
      on an 8% salt diet, indicating an enhanced salt sensitivity by OLM. Co-treatment
      with HCTZ reduced the salt sensitivity of OLM. The urinary level of the oxidative
      stress marker was increased by an 8% salt diet and was not altered by either OLM
      alone or in combination with HCTZ. However, OLM attenuated the salt-induced renal
      NAD(P)H (nicotinamide adenine dinucleotide phosphate) oxidase activity. These
      results indicate that AT1 receptor blockade increases salt sensitivity, which is
      reversed by diuretics. We conclude that OLM and HCTZ could be a useful
      combination for reduction of blood pressure even under high salt intake without
      changes in urinary oxidative stress levels.

PMID- 19407825
TI  - Role of renin-angiotensin system in adipose tissue dysfunction.
AB  - Blockade of angiotensin II type 1 (AT(1)) receptor improves insulin sensitivity
      and diabetic condition. In short-term regulation, angiotensin II changes lipid
      metabolism and in long-term regulation, it affects insulin sensitivity and
      adipocyte differentiation in adipose tissue. These effects are mainly mediated by
      AT(1) receptor. AT(1) receptor blocker improves insulin sensitivity and induces
      adipocyte differentiation by increasing peroxisome proliferator-activated
      receptor-gamma (PPARgamma) and transcription factors in adipose tissue in
      diabetic and atherosclerotic models. Clinical studies indicate that AT(1)
      receptor blockers prevent the new onset of diabetes and improve insulin
      sensitivity. On the other hand, AT(2) receptor stimulation appears to cause
      antagonistic actions against AT(1) receptor signaling. Although further
      investigations are necessary on the AT(2) receptor function in adipose tissue,
      studies using AT(2) receptor agonists, in addition to those using AT(1) receptor
      blockers, would contribute to the treatment of metabolic syndrome and associated
      pathological disorders.

PMID- 19407826
TI  - Superoxide is the major reactive oxygen species regulating autophagy.
AB  - Autophagy is involved in human diseases and is regulated by reactive oxygen
      species (ROS) including superoxide (O(2)(*-)) and hydrogen peroxide (H(2)O(2)).
      However, the relative functions of O(2)(*-) and H(2)O(2) in regulating autophagy
      are unknown. In this study, autophagy was induced by starvation, mitochondrial
      electron transport inhibitors, and exogenous H(2)O(2). We found that O(2)(*-) was
      selectively induced by starvation of glucose, L-glutamine, pyruvate, and serum
      (GP) whereas starvation of amino acids and serum (AA) induced O(2)(*-) and
      H(2)O(2). Both types of starvation induced autophagy and autophagy was inhibited
      by overexpression of SOD2 (manganese superoxide dismutase, Mn-SOD), which reduced
      O(2)(*-) levels but increased H(2)O(2) levels. Starvation-induced autophagy was
      also inhibited by the addition of catalase, which reduced both O(2)(*-) and
      H(2)O(2) levels. Starvation of GP or AA also induced cell death that was
      increased following treatment with autophagy inhibitors 3-methyladenine, and
      wortamannin. Mitochondrial electron transport chain (mETC) inhibitors in
      combination with the SOD inhibitor 2-methoxyestradiol (2-ME) increased O(2)(*-)
      levels, lowered H(2)O(2) levels, and increased autophagy. In contrast to
      starvation, cell death induced by mETC inhibitors was increased by 2-ME. Finally,
      adding exogenous H(2)O(2) induced autophagy and increased intracellular O(2)(*-)
      but failed to increase intracellular H(2)O(2). Taken together, these findings
      indicate that O(2)(*-) is the major ROS-regulating autophagy.

PMID- 19407827
TI  - The pleiotropic effect of TRAIL on tumor-like synovial fibroblasts from
      rheumatoid arthritis patients is mediated by caspases.
AB  - The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has
      gained much attention as a possible therapeutic reagent for the treatment of
      tumors, as TRAIL was originally described to induce apoptosis specifically in
      cancer cells, but not in normal cells. Fibroblast-like synoviocytes (FLS) in
      rheumatoid arthritis (RA) patients exhibit tumor-like features and we have
      described earlier that TRAIL induces apoptosis only in a subset of RA FLS, but an
      induction of proliferation in the surviving cells. This observation corresponds
      to the pleiotropic effects of TRAIL observed on primary human tumor cells. Here,
      we describe that the PI3 kinase/Akt-signaling pathway, but not that of the MAP
      kinases ERK and p38, protects RA FLS from TRAIL-induced apoptosis by modulating
      the expression of the cell survival regulators p21, XIAP, Mcl-1 and RIP.
      Moreover, we found that not only TRAIL-induced apoptosis, but also TRAIL
      triggered proliferation in RA FLS is mediated by caspases with a crucial role for
      caspase 8. TRAIL was found to induce degradation of p21 and p27 that was caspase
      dependent, but independent of the ERK, p38 and PI3 kinase/Akt-signaling pathways.
      The finding that TRAIL-triggered proliferation and apoptosis share intracellular
      routes has to be taken in consideration in defining therapeutic strategies on the
      basis of the administration of TRAIL.

PMID- 19407828
TI  - Induction of Bim limits cytokine-mediated prolonged survival of neutrophils.
AB  - Under inflammatory conditions, neutrophil apoptosis is delayed due to survival
      factor exposure, a mechanism that prevents the resolution of inflammation. One
      important proinflammatory cytokine involved in the regulation of neutrophil
      survival/activation is granulocyte-macrophage colony-stimulating factor (GM-CSF).
      Although GM-CSF mediates antiapoptotic effects in neutrophils, it does not
      prevent apoptosis, and the survival effect is both time dependent and limited.
      Here, we identified the proapoptotic Bcl-2 family member Bim as an important
      lifespan limiting molecule in neutrophils, particularly under conditions of
      survival factor exposure. Strikingly, GM-CSF induced Bim expression in both human
      and mouse neutrophils that was blocked by pharmacological inhibition of
      phosphatidylinositol-3 kinase (PI3K). Increased Bim expression was also seen in
      human immature bone marrow neutrophils as well as in blood neutrophils from
      septic shock patients; both cell populations are known to be exposed to GM-CSF
      under in vivo conditions. The functional role of Bim was investigated using Bim
      deficient mouse neutrophils in the presence and absence of the survival cytokines
      interleukin (IL)-3 and GM-CSF. Lack of Bim expression resulted in a much higher
      efficacy of the survival cytokines to block neutrophil apoptosis. Taken together,
      these data demonstrate a functional role for Bim in the regulation of neutrophil
      apoptosis and suggest that GM-CSF and other neutrophil hematopoietins initiate a
      proapoptotic counterregulation that involves upregulation of Bim.

PMID- 19407829
TI  - Molecular cloning of t(2;7)(p24.3;p14.2), a novel chromosomal translocation in
      myelodysplastic syndrome-derived acute myeloid leukemia.
AB  - In this study, we report the molecular structure of the breakpoint region in a
      new chromosomal translocation, t(2;7)(p24.3;p14.2), in a case of acute myeloid
      leukemia transformed from myelodysplastic syndrome (MDS). An extensive
      fluorescence in situ hybridization (FISH) analysis showed that NAG (2p24.3) and
      ELMO1 (7p14.2) were involved at the breakpoints of t(2;7)(p24.3;p14.2).
      Furthermore, we detected a novel chimeric transcript consisting of NAG and ELMO1.
      Interestingly, this transcript encoded a truncated molecular form of 3'ELMO1 as
      the result of a frameshift caused by the chromosomal translocation. Although this
      study does not provide direct evidence that a defect in NAG-ELMO1 plays a role in
      the pathogenesis or the leukemic change in MDS, it does suggest that defects in
      NAG-ELMO1 potentially contributed to the leukemic progression in this case.

PMID- 19407830
TI  - MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission.
AB  - The modification of proteins by the small ubiquitin-like modifier (SUMO) is known
      to regulate an increasing array of cellular processes. SUMOylation of the
      mitochondrial fission GTPase dynamin-related protein 1 (DRP1) stimulates
      mitochondrial fission, suggesting that SUMOylation has an important function in
      mitochondrial dynamics. The conjugation of SUMO to its substrates requires a
      regulatory SUMO E3 ligase; however, so far, none has been functionally associated
      with the mitochondria. By using biochemical assays, overexpression and RNA
      interference experiments, we characterized the mitochondrial-anchored protein
      ligase (MAPL) as the first mitochondrial-anchored SUMO E3 ligase. Furthermore, we
      show that DRP1 is a substrate for MAPL, providing a direct link between MAPL and
      the fission machinery. Importantly, the large number of unidentified
      mitochondrial SUMO targets suggests a global role for SUMOylation in
      mitochondrial function, placing MAPL as a crucial component in the regulation of
      multiple conjugation events.

PMID- 19407833
TI  - Serratia marcescens endophthalmitis associated with intravitreal injections of
      bevacizumab.
AB  - PURPOSE: To report two cases of Serratia marcescens endophthalmitis related to
      presumed aliquot drug contamination, and to determine the incidence of acute
      endophthalmitis after intravitreal injection of bevacizumab. METHODS: A
      retrospective chart review of 2020 consecutive intravitreal bevacizumab injection
      (IVBI) cases at the three affiliated hospitals of Seoul National University (A,
      B, and C) was carried out between 12 October 2006, and 31 January 2008.
      Bevacizumab was retrieved multiple times from a single original vial as needed
      and then discarded on the same day at hospital A and C, or prepared as a single
      dose aliquot vial at a compounding pharmacy in the hospital B. RESULTS: The
      incidence of endophthalmitis after IVBI was 2/2020 (0.099%). Two patients
      receiving IVBI on the same day, but by different surgeons in different sites in
      hospital B, developed acute endophthalmitis. S. marcescens was isolated from the
      vitreous sample of the two patients. Molecular typing with pulsed field gel
      electrophoresis showed that the organisms were of the same strain, which
      suggested that the drug was contaminated at the pharmacy. CONCLUSIONS:
      Endophthalmitis is a rare complication after IVBI and can be caused by
      contaminated aliquot drug. Serratia is one of the causative organisms of acute
      endophthalmitis, which can have devastating consequences, despite the treatment.
      A compounding pharmacy in a hospital might not be able to guarantee that
      aliquoted drug is free of contamination for the IVBI.

PMID- 19407834
TI  - Should Avastin be used to treat age-related macular degeneration in the NHS?-
      Yes.

PMID- 19407835
TI  - Topiramate and asymptomatic ocular angle narrowing: a prospective pilot study.
AB  - PURPOSE: To investigate whether subclinical ciliochoroidal effusion and resulting
      asymptomatic angle narrowing occurs in patients taking topiramate, by ultrasound
      biomicroscopy (UBM). METHODS: Chinese patients aged 18-75 years for whom
      topiramate was indicated were recruited. Examinations including UBM were
      performed before and 4 weeks after commencement of topiramate. RESULTS: In this
      pilot of 20 eyes of 20 patients, there were no statistically significant changes
      in the angle parameters noted on gonioscopy or UBM, including anterior chamber
      depth, angle-opening distance at 500 mum, trabecular ciliary process distance,
      trabecular-iris angle, and scleral thickness. CONCLUSION: Short-term use of
      topiramate does not induce asymptomatic angle narrowing.

PMID- 19407836
TI  - Should avastin be used to treat age-related macular degeneration in the NHS?--No.

PMID- 19407837
TI  - Relationship between refraction and allergic conjunctivitis.

PMID- 19407838
TI  - Haemorrhagic hypertensive hypopyon uveitis in early immune reactivation uveitis.

PMID- 19407839
TI  - Interpretation of the outer retina with high-resolution optical coherence
      tomography.

PMID- 19407840
TI  - Surgeon age and operative outcomes for primary rhegmatogenous retinal detachment:
      a 3-year nationwide population-based study.
AB  - PURPOSE: The aim was to study the association of surgeon age with operative
      outcomes for primary rhegmatogenous retinal detachment (RRD) in Taiwan. METHODS:
      A total of 7427 adult patients of primary RRD who were treated by 284
      ophthalmologists with scleral buckling (SB), pars plana vitrectomy (PPV), or
      their combination from 2002 to 2004 were identified in the Taiwan National Health
      Insurance Research Database. The adjusted odds ratios (OR) of 180-day readmission
      between ophthalmologist age groups were calculated. RESULTS: For SB, patients
      treated by ophthalmologists aged >or=51 years had a greater 180-day readmission
      rate (OR=1.44, 95% confidence interval (CI)=1.01-2.07, P<0.05) than those treated
      by ophthalmologists aged 41-50 years. For PPV, patients treated by
      ophthalmologists aged <or=40 years had a lower 180-day readmission rate than
      those treated by ophthalmologists aged 41-50 and >or=51 years (OR=0.58 and 0.22,
      95% CI=0.47-0.71 and 0.13-0.63, P<0.001 and <0.001, respectively). For PPV+SB,
      patients treated by ophthalmologists aged >or=51 years had a higher 180-day
      readmission rate than those treated by ophthalmologists aged <or=40 and 41-50
      years (OR=3.32 and 2.45, 95% CI=2.29-4.21 and 1.36-4.40, P<0.01 and <0.01,
      respectively). The absolute differences in the 180-day readmission rate by
      surgeon age ranged from -0.1 to 3.2%. The proportions of selecting primary SB
      (without PPV) as the treatment modality were 33.1, 35.6, and 70.6% for the <or=40
      , 41-to 50-, and >or=51-year groups, respectively. CONCLUSIONS: Surgeon age is a
      relatively weak predictor for the outcomes of primary RRD surgery in aggregate in
      Taiwan and certainly not appropriate for discriminating performance among
      individual surgeons.

PMID- 19407841
TI  - Performance of GDx and HRT in the Finnish Evidence-Based Guideline for Open-Angle
      Glaucoma.
AB  - AIM: To compare the performance of Heidelberg retina tomograph (HRT) and scanning
      laser polarimetry (GDx) with photographic evaluation of the optic nerve head
      (ONH) and retinal nerve fiber layer (RNFL) in the application of the Finnish
      Evidence-Based Guideline for Open-Angle Glaucoma. METHODS: A total of 41 control
      participants and 312 patients referred for glaucoma evaluation were included in
      the study. All the participants underwent ophthalmic evaluation, ONH
      stereophotography, monochromatic RNFL photography, HRT, optical coherence
      tomography, and GDx evaluation. Participants were classified on the basis of
      stereophotographic or imaging device results based by applying the Finnish
      Guideline. RESULTS: Agreement between the stereophotographic evaluation and that
      on the basis of the imaging devices was 52.9%. Classification of patients with
      similar management advice on the basis of these evaluations had 56.4% agreement.
      The specificity of the Finnish guideline for detecting normal patients was 78%
      (stereophotography) and 83% (imaging devices). Optic disc size interfered with
      the diagnosis in patients evaluated using the HRT3 glaucoma probability score.
      Structural changes were more frequently detected before functional changes.
      CONCLUSION: The Finnish Evidence-Based Guideline for Open-Angle Glaucoma is
      useful for classifying normal participants and patients with suspected glaucoma
      or glaucoma through either conventional stereophotographic evaluation of the
      neuroretinal structures or with the new imaging devices.

PMID- 19407842
TI  - Therapeutic effect of bevacizumab injected into the silicone oil in eyes with
      neovascular glaucoma after vitrectomy for advanced diabetic retinopathy.
AB  - PURPOSE: To evaluate the effect of intra-silicone injection of bevacizumab for
      the treatment of neovascular glaucoma (NVG) after vitrectomy for advanced
      proliferative diabetic retinopathy. METHODS: Bevacizumab was injected into the
      silicone oil in five pseudophakic eyes of five patients with NVG. The iris
      neovascularization (INV) and NVG had developed 1.5-4 months after vitrectomy and
      silicone oil tamponade. The main outcome measures were regression of INV,
      intraocular pressure and visual acuity. RESULTS: In all eyes, INV regressed and
      intraocular pressure was controlled within 7 days. Visual acuity improved in all
      eyes. In one patient, INV and NVG recurred 10 weeks after the injection and was
      successfully treated with a repeat intra-silicone bevacizumab injection.
      CONCLUSION: Intra-silicone injection of bevacizumab is effective in the treatment
      of patients with INV and NVG after vitrectomy for advanced proliferative diabetic
      retinopathy.

PMID- 19407844
TI  - Fine-needle aspiration biopsy in lacrimal gland pleomorphic adenoma.

PMID- 19407845
TI  - Comparisons of intraocular pressure measurements: Goldmann applanation tonometry,
      noncontact tonometry, Tono-Pen tonometry, and dynamic contour tonometry.
AB  - AIMS: To compare intraocular pressure (IOP) readings between Tono-Pen tonometry
      and GAT, between noncontact tonometry (NCT) and GAT, and between dynamic contour
      tonometry (DCT) and Goldmann applanation tonometry (GAT). The correlation between
      IOP reading and possible confounder was identified. METHODS: This observational
      cross-sectional study enrolled sixty-two healthy subjects. All IOP and ocular
      pulse amplitude (OPA) measurements were taken by a single ophthalmologist; mean
      keratometric power (MK), central corneal thickness (CCT), and lens thickness (LT)
      were measured by a single experienced technician. RESULTS: Stepwise multiple
      regression analysis indicated that GAT (P=0.017) and DCT (P=0.002) readings
      correlated positively with MK; GAT, NCT, and Tono-Pen readings correlated
      positively with CCT (P<0.05); NCT (P=0.035), and DCT (P=0.016) readings
      correlated negatively with LT; GAT (P=0.006) and Tono-Pen (P=0.009) readings
      correlated positively with OPA. CONCLUSIONS: The K, CCT, LT, and OPA are
      confounders in tonometry readings.

PMID- 19407846
TI  - Prevalence of myocilin gene mutations in a novel UK cohort of POAG patients.
AB  - PURPOSE: To identify the prevalence of myocilin gene mutations in a UK glaucoma
      cohort. METHODS: Primary open-angle (POAG) and normal tension glaucoma patients
      were recruited from the Southampton University Hospital Trust Eye Clinic and
      satellite regional glaucoma clinics. Phenotype data relating to disease history
      and other potential risk factors were recorded and blood samples collected for
      each consenting participant. Point mutation analysis of the myocilin gene was
      carried out using six overlapping PCR fragments covering the entire coding
      sequence of the gene. A total of 316 POAG samples were examined of which 7 (2.2
      %) tested positive for disease-causing mutations in this gene. One of these seven
      non-synonymous mutations represented a previously unreported amino-acid
      substitution of cysteine for arginine at codon 296 (p.R296C) of the myocilin
      protein. CONCLUSIONS: This study identifies a 2.2% prevalence of myocilin
      mutations in a cohort of ethnically homogenous glaucoma patients selected from a
      UK ophthalmic clinic. A novel myocilin mutation is also described. This study
      identifies that myocilin genetic screening is feasible in NHS glaucoma clinics
      for genetic counselling and cascade testing of relatives of patients affected by
      myocilin glaucoma.

PMID- 19407847
TI  - Surveillance of traumatic optic neuropathy in the UK.
AB  - AIMS: The aim of this study is to provide epidemiological data on the incidence,
      aetiology, management, and visual outcome in traumatic optic neuropathy (TON) in
      the UK. METHODS: Patients with TON were identified prospectively by population
      based active surveillance through the British Ophthalmic Surveillance Unit over a
      2-year period with data obtained from an incident questionnaire and follow-up
      questionnaire sent to positive reporters. RESULTS: Incident and follow-up data
      were available on 121 and 97 (80%) patients, respectively. The minimum estimated
      incidence was 1.005 per million. Leading causes included falls (25.6%), road
      traffic accidents (RTAs) (21.5%), and assaults (20.7%). The median age was 31
      years. There were 95 (78.5%) men. Presenting visual acuity (VA) was 6/60 or worse
      in 85 (70%) patients, with 43 patients (36%) with no perception of light.
      Associated injuries included 47 (39%) orbital wall fractures, 37 (31%) closed
      globe injuries, 23 (19%) ocular adnexal injuries, 23 (19%) skull fractures, and
      18 (16%) intracranial bleeding. Sixty-five percent (75/116) received no acute
      treatment and 35% (41/116) received steroids and/or surgery. Of the treated
      group, 24% (8/33) and of the untreated group 20% (11/56) improved three lines or
      more of VA (P=0.61). Prompt ophthalmic examination (P=0.002), orbital fracture
      (P=0.046), high Glasgow Coma Scale (GCS) score (P=0.023), and poor initial VA
      (P=0.009) were associated with increased likelihood of treatment. Poor initial VA
      (P<0.001), orbital fracture (P=0.004), and significant head injury (P=0.038) were
      associated with poor visual outcome. CONCLUSIONS: This study suggested that young
      men were at greatest risk of TON. We detected a trend towards conservative
      management of this condition in the UK. TON was associated with significant
      ocular, orbital, and head injuries that highlighted the need for
      multidisciplinary management.

PMID- 19407848
TI  - In vitro and in vivo antitrypanosomal activities of three peptide antibiotics:
      leucinostatin A and B, alamethicin I and tsushimycin.
AB  - In the course of our screening for antitrypanosomal compounds from soil
      microorganisms, as well as from the antibiotics library of the Kitasato Institute
      for Life Sciences, we found three peptide antibiotics, leucinostatin (A and B),
      alamethicin I and tsushimycin, which exhibited potent or moderate
      antitrypanosomal activity. We report here the in vitro and in vivo
      antitrypanosomal properties and cytotoxicities of leucinostatin A and B,
      alamethicin I and tsushimycin compared with suramin. We also discuss their
      possible mode of action. This is the first report of in vitro and in vivo
      trypanocidal activity of leucinostatin A and B, alamethicin I and tsushimycin.

PMID- 19407849
TI  - RNA interference-mediated knockdown of p21(WAF1) enhances anti-tumor cell
      activity of oncolytic adenoviruses.
AB  - The ability of oncolytic adenoviruses to replicate in and lyse cancer cells
      offers a potential therapeutic approach. However, selectivity and efficacy of
      adenovirus replication need to be improved. In this study, we present that loss
      of p21(WAF1) promotes adenovirus replication and more effective cell killing. To
      test our hypothesis, we took HCT116 colon cancer cell lines carrying deletions of
      either p21(WAF1) or p53, and infected these cell lines with wild-type adenovirus
      (WtD) or the oncolytic adenoviruses, ONYX-015 and Delta-24. We found that WtD,
      ONYX-015 and Delta-24 induced stronger cytopathic effects in HCT116 p21-/- cells
      compared with HCT116-WT cells. This was accompanied by increased virus
      production. siRNA-mediated knockdown of p21(WAF1), and similarly of p27(KIP1), in
      HCT116-WT cells also enhanced replication of and cell killing by these viruses.
      Furthermore, we found that TE7, an esophageal carcinoma cell line, also showed a
      strong cell-killing effect and virus production when p21(WAF1) expression was
      suppressed by RNA interference before adenoviruses infection. Also, H1299 and DU
      145 cells transfected with p21(WAF1) siRNA showed higher virus production after
      ONYX-015 and Delta-24 infections. These observations suggest that p21(WAF1) plays
      a role in mediating replication of oncolytic viruses with potential implications
      for adenoviral therapy of cancer.

PMID- 19407850
TI  - HLA-G polymorphisms in women with squamous intraepithelial lesions harboring
      human papillomavirus.
AB  - Human papillomavirus (HPV) infection is etiologically associated with low- (LSIL)
      and high-grade squamous intraepithelial lesions (HSIL) and with cervical cancer.
      The progression or regression of the lesions may depend, among other factors, on
      the host heritable immune response. Because human leukocyte antigen (HLA)-G
      molecules are involved in the modulation of innate and adaptive immune responses,
      and because no previous studies have evaluated HLA-G polymorphism in patients
      with SIL, we conducted a study to assess the association between HLA-G
      polymorphisms and cervical lesions harboring HPV infection. Cervico-vaginal
      scrapings and blood samples were collected from 125 women with SIL (68 LSIL and
      57 HSIL) and from 94 healthy women without HPV infection and cytological
      abnormalities. HPV type and HLA-G polymorphisms in exons 2, 3 and 8 (14 bp
      insertion/deletion) were evaluated by PCR methodology, and digested with
      restriction endonucleases. The Genepop software and the EM and PHASE algorithms
      were used for statistical analysis. A significant protective association was
      observed between the presence of the G(*)0103 allele and SIL and between the
      G0101/G0104 genotype and HSIL in the group of patients compared to control. The
      presence of the G0104/+14 bp and G0104/-14 bp haplotypes conferred susceptibility
      to SIL compared to control. In addition, patients possessing the G0104/+14 bp
      haplotype and harboring HPV-16 and -18 co-infections were particularly associated
      with HSIL. These findings suggest that HLA-G polymorphisms may be associated with
      HPV infection and SIL, consequently representing a profile of predisposition to
      cervical cancer.

PMID- 19407852
TI  - Cell polarity protein Lgl2 is lost or aberrantly localized in gastric dysplasia
      and adenocarcinoma: an immunohistochemical study.
AB  - The diagnosis of gastric epithelial dysplasia, a precursor lesion of gastric
      adenocarcinoma, is hindered by interobserver variability and by its resemblance
      to regenerative changes. Loss of cell polarity, a histological feature of gastric
      epithelial dysplasia, may be difficult to ascertain, especially in the setting of
      inflammation or injury. A biomarker of cell polarity could be useful in diagnosis
      of dysplasia, but has not been reported. The Lethal giant larvae (lgl) gene
      controls apical-basal polarity of epithelial cells in Drosophila, and has
      properties of a tumor-suppressor gene. Two homologs, lgl1 and lgl2, are present
      in mammals and lgl2 mRNA is highly expressed in the stomach. The goal of our
      study was to test the hypothesis that Lgl2 protein expression and/or localization
      are disrupted in gastric epithelial dysplasia and adenocarcinoma. Routinely
      processed pathology specimens including 94 benign mucosae of digestive organs, in
      addition to 36 reactive gastropathy, 57 gastric epithelial dysplasia, and 77
      gastric adenocarcinomas, were immunostained for Lgl2 protein. All normal,
      reactive, and chronically inflamed gastric epithelia showed basolateral Lgl2
      staining. Normal esophageal, duodenal, colonic, biliary, and pancreatic duct
      mucosae, as well as gastric intestinal metaplasia, did not express Lgl2. All but
      one case each of gastric epithelial dysplasia and adenocarcinoma showed either
      complete loss of anti-Lgl2 immunoreactivity or diffuse, mostly weak, cytoplasmic
      staining. Complete loss of immunoreactivity was significantly more often observed
      in diffuse-type than in intestinal-type adenocarcinomas (79 vs 48%,
      respectively). Our data suggest that Lgl2 expression is either aberrantly
      localized or lost in gastric epithelial dysplasia and adenocarcinoma, whereas it
      is maintained in reactive gastric mucosa. We propose that Lgl2 may be a potential
      marker to rule out gastric epithelial dysplasia and adenocarcinoma in diagnostic
      specimens. However, the consistently negative anti-Lgl2 immunoreactivity seen in
      intestinal metaplasia does not allow differentiation of dysplasia from intestinal
      metaplasia with reactive change.

PMID- 19407851
TI  - Fluorescence in situ hybridization study shows association of PTEN deletion with
      ERG rearrangement during prostate cancer progression.
AB  - The link between ERG rearrangement and PTEN (phosphatase and tensin homolog
      deleted on chromosome 10) deletion is unclear in prostate cancer progression.
      Using fluorescence in situ hybridization, we systematically validated the
      frequency and distribution of ERG and PTEN aberrations in a cohort of 73 benign
      prostate tissues, 59 high-grade prostatic intraepithelial neoplasia (HGPIN) foci,
      281 localized prostate cancer and 47 androgen-independent metastatic prostate
      cancer patients. Overall, ERG rearrangement was present in 15% (5/33) of HGPIN,
      45% (121/267) of localized cancers and 35% (15/43) of metastases. By contrast,
      PTEN deletion was identified in 9% (3/33) of HGPIN, 17% (42/251) of localized
      cancers and 54% (22/41) of metastases, of which 0%, 40% (17/42) and 45% (10/22)
      were homozygous, respectively. Concomitance of ERG rearrangement and PTEN
      deletion was observed in a subset of HGPIN. Significantly, association between
      PTEN deletion and ERG rearrangement was present both in localized cancers
      (P=0.0008) and metastases (P=0.02). Further, immunohistochemistry revealed
      significant correlation of decreased PTEN protein expression with PTEN genomic
      deletion both in localized and metastatic cancer. Of note, ERG aberration, but
      not PTEN deletion, was consistently identical both in localized cancer and
      adjacent HGPIN. Similarly, whereas all metastases (41/41, 100%) shared the same
      ERG status across multiple sites from the same patient, 5% (2/41) of cases showed
      discordance for PTEN deletion status across multiple sites. Collectively, our
      data support PTEN deletion as a late genetic event in human prostate cancer,
      presumably a 'second hit' after ERG rearrangement. PTEN deletion and ERG
      rearrangement may cooperate, but contribute at different stages, in prostate
      cancer progression.

PMID- 19407853
TI  - Expression of insulin-like growth factor 2 in mesenchymal neoplasms.
AB  - The insulin-like growth factor (IGF) system plays an important role in the growth
      and development of cells and has been implicated in oncogenesis and tumor
      progression. Gene expression profiling studies on limited numbers of specimens
      have shown high expression of IGF2, encoding the activating ligand for this
      system, in gastrointestinal stromal tumors (GISTs) and in synovial sarcomas. This
      data may have concrete clinical implications, as several reports exist of
      patients with GISTs suffering from severe hypoglycemia, a predicted effect of
      IGF2. Furthermore, new drugs targeting IGF signaling are entering clinical
      trials. The purpose of this study is to survey IGF2 expression at the protein
      level on a broad number of mesenchymal tumors representing all major diagnostic
      classes. By immunostaining tissue microarrays, results were obtained for 51
      diagnostic categories of bone and soft-tissue tumors representing 1288 cases.
      Distinct membranous and/or cytoplasmic IGF2 immunoreactivity was assessed
      according to published criteria. Solitary fibrous tumors had the highest
      expression. Of 20 tumor types represented by more than 10 cases, synovial
      sarcomas, myxoid liposarcomas, GISTs, malignant peripheral nerve sheath tumors,
      chondrosarcomas, undifferentiated pleomorphic sarcomas (MFH), Ewing's sarcomas
      and tenosynovial giant cell tumors showed high levels of expression in more than
      20% of cases. Of the 445 GIST cases with clinical information, those with high
      expression of IGF2 had a significantly worse outcome than those with low or no
      expression. IGF2 protein expression among mesenchymal tumors is largely
      consistent with gene expression studies and suggests a potential for molecular
      therapy targeting the IGF signaling pathway system in these neoplasms.

PMID- 19407854
TI  - Presence of cancer-associated fibroblasts inversely correlates with Schwannian
      stroma in neuroblastoma tumors.
AB  - Stromal cells have a central function in the regulation of tumor angiogenesis.
      Recent studies have shown that stromal myofibroblasts (cancer-associated
      fibroblasts) actively promote tumor growth and enhance tumor angiogenesis in many
      types of adult carcinomas. To evaluate the function cancer-associated fibroblasts
      have in neuroblastoma angiogenesis and investigate their relationship to stromal
      Schwann cells, we quantified cancer-associated fibroblasts in 60 primary
      neuroblastoma tumors and in a novel neuroblastoma xenograft model in which murine
      Schwann cells were induced to infiltrate into the tumor stroma. Tumor sections
      were examined for presence of microvascular proliferation, a hallmark of tumor
      angiogenesis. Cancer-associated fibroblasts were characterized by positive
      immunostaining for alpha-smooth muscle actin (alpha-SMA) and were distinguished
      from pericytes by staining negatively for high-molecular-weight caldesmon. alpha
      SMA-positive cells were quantified and their number was defined as high when
      >1.0% of the area was positive. Associations between high cancer-associated
      fibroblast number, microvascular proliferation and established prognosticators
      were analyzed. High numbers of cancer-associated fibroblasts were associated with
      Schwannian stroma-poor histopathology and microvascular proliferation. Thirty
      seven (80%) of the 46 Schwannian stroma-poor tumors had high numbers of cancer
      associated fibroblasts in the tumor stroma compared to only 2 (14%) of the 14
      Schwannian stroma-rich/dominant tumors (P<0.001). Thirty-three (89%) of 37 tumors
      with microvascular proliferation had high numbers of cancer-associated
      fibroblasts compared to 9 (40%) of 22 tumors without microvascular proliferation
      (P<0.001). In the xenografts with infiltrating Schwann cells (n=10), the number
      of cancer-associated fibroblasts per mm(2) was approximately sevenfold less than
      in the control xenografts without stromal Schwann cells (n=9) (mean of 51+/-30 vs
      368+/-105, respectively; P<0.001). Thus, cancer-associated fibroblasts were
      inversely associated with presence of Schwann cells, suggesting that Schwann
      cells may prevent the activation of fibroblasts. A deeper understanding of the
      function cancer-associated fibroblasts have in neuroblastoma angiogenesis may
      guide future development of stroma-directed therapeutic strategies.

PMID- 19407855
TI  - Analysis of the fibroblastic growth factor receptor-RAS/RAF/MEK/ERK
      ETS2/brachyury signalling pathway in chordomas.
AB  - Chordomas are rare primary malignant bone tumours that derive from notochord
      precursor cells and express brachyury, a molecule involved in notochord
      development. Little is known about the genetic events responsible for driving the
      growth of this tumour, but it is well established that brachyury is regulated
      through fibroblastic growth factor receptors (FGFRs) through RAS/RAF/MEK/ERK and
      ETS2 in ascidian, Xenopus and zebrafish, although little is known about its
      regulation in mammals. The aim of this study was to attempt to identify the
      molecular genetic events that are responsible for the pathogenesis of chordomas
      with particular focus on the FGFR signalling pathway on the basis of the evidence
      in the ascidian and Xenopus models that the expression of brachyury requires the
      activation of this pathway. Immunohistochemistry showed that 47 of 50 chordomas
      (94%) expressed at least one of the FGFRs, and western blotting showed
      phosphorylation of fibroblast growth factor receptor substrate 2 alpha
      (FRS2alpha), an adaptor signalling protein, that links FGFR to the
      RAS/RAF/MEK/ERK pathway. Screening for mutations in brachyury (all coding exons
      and promoter), FGFRs 1-4 (previously reported mutations), KRAS (codons 12, 13,
      51, 61) and BRAF (exons 11 and 15) failed to show any genetic alterations in 23
      chordomas. Fluorescent in situ hybridisation analysis on FGFR4, ETS2 and
      brachyury failed to show either amplification of these genes, although there was
      minor allelic gain in brachyury in three tumours, or translocation for ERG and
      ETS2 loci. The key genetic events responsible for the initiation and progression
      of chordomas remain to be discovered.

PMID- 19407857
TI  - NTP-CERHR monograph on the potential human reproductive and developmental effects
      of di (2-ethylhexyl) phthalate (DEHP).
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an updated evaluation of the potential for DEHP to
      cause adverse effects on reproduction and development in humans. The first CERHR
      expert panel evaluation of DEHP was completed in 2000 by the Phthalates Expert
      Panel. CERHR selected DEHP for an updated evaluation because of: (1) widespread
      human exposure, (2) public and government interest in adverse health effects, (3)
      recently available human exposure studies, and (4) the large number of relevant
      toxicity papers published since the earlier evaluation. DEHP (CAS RN: 117-81-7)
      is a high production volume chemical used as a plasticizer of polyvinyl chloride
      in the manufacture of a wide variety of consumer goods, such as building
      products, car products, clothing, food packaging, children's products (but not in
      toys intended for mouthing), and in medical devices made of polyvinyl chloride.
      The public can be exposed to DEHP by ingesting food, drink or dust that has been
      in contact with DEHP-containing materials, by inhaling contaminated air or dust,
      or by undergoing a medical procedure that uses polyvinyl chloride medical tubing
      or storage bags. It is estimated that the general population of the United States
      is exposed to DEHP levels ranging from 1 to 30 microg/kg bw/day (micrograms per
      kilogram body weight per day). The results of this DEHP update evaluation are
      published in an NTP-CERHR monograph that includes: (1) the NTP Brief, (2) the
      Expert Panel Update on the Reproductive and Developmental Toxicity of DEHP, and
      (3) public comments on the expert panel report. The NTP reached the following
      conclusions on the possible effects of exposure to DEHP on human development and
      reproduction. Note that the possible levels of concern, from lowest to highest,
      are negligible concern, minimal concern, some concern, concern, and serious
      concern. There is serious concern that certain intensive medical treatments of
      male infants may result in DEHP exposure levels that adversely affect development
      of the male reproductive tract. DEHP exposure from medical procedures in infants
      was estimated to be as high as 6000 microg/kg bw/day. There is concern for
      adverse effects on development of the reproductive tract in male offspring of
      pregnant and breast feeding women undergoing certain medical procedures that may
      result in exposure to high levels of DEHP. There is concern for effects of DEHP
      exposure on development of the male reproductive tract for infants less than one
      year old. Diet, mouthing of DEHP-containing objects, and certain medical
      treatments may lead to DEHP exposures that are higher than those experienced by
      the general population. There is some concern for effects of DEHP exposure on
      development of the reproductive tract of male children older than one year. As in
      infants, exposures of children to DEHP may be higher than in the general
      population. There is some concern for adverse effects of DEHP exposure on
      development of the male reproductive tract in male offspring of pregnant women
      not medically exposed to DEHP. Although DEHP exposures are assumed to be the same
      as for the general population, the developing male reproductive tract is
      sensitive to the adverse effects of DEHP. There is minimal concern for
      reproductive toxicity in adults exposed to DEHP at 1 - 30 microg/kg bw/day. This
      level of concern is not altered for adults medically exposed to DEHP. NTP will
      transmit the NTP-CERHR Monograph on DEHP to federal and state agencies,
      interested parties, and the public and it will be available in electronic PDF
      format on the CERHR web site http://cerhr.niehs.nih.gov and in printed text or CD
      ROM from the CERHR.

PMID- 19407856
TI  - Intercepting early pelvic serous carcinoma by routine pathological examination of
      the fimbria.
AB  - Recent evidence indicates that the distal fallopian tube is the principal site of
      early serous cancer in women with a hereditary risk for ovarian cancer. Moreover,
      the fimbria is involved by early cancer in a significant minority of pelvic
      serous carcinomas, irrespective of whether the patient has a hereditary BRCA1 or
      BRCA2 mutation. In addition, the distal tube has been identified occasionally as
      a site of concurrent endometrioid tumors in women with endometrial carcinoma.
      Although the risk of sporadic fimbrial tumors in otherwise healthy women without
      genetic risk is unknown, routine histological examination of the fimbria provides
      the opportunity to determine the risk of such an event. To illustrate this point,
      a case of a woman who underwent surgery for an ovarian fibroma is presented. The
      distal tube was submitted, and found to harbor a focus of serous tubal
      intraepithelial carcinoma (STIC) with a 2-mm invasive tumor. Incidentally
      discovered carcinomas underscore the potential risk, albeit low, of concurrent
      unsuspected malignancy in the distal fallopian tube and emphasize the importance
      of routine pathological examination of the fimbria in all salpingectomies. The
      rationale for this strategy, and its potential effect on early detection and in
      uncovering persons or families potentially at risk for ovarian cancer, is
      discussed.

PMID- 19407858
TI  - NTP-CERHR monograph on the potential human reproductive and developmental effects
      of hydroxyurea.
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for hydroxyurea to
      cause adverse effects on reproduction and development in humans. Hydroxyurea is a
      drug used to treat cancer, sickle cell disease, and thalassemia. It is the only
      treatment for sickle cell disease in children, aside from blood transfusion and,
      in severe cases, hematopoietic stem cell transplantation. Hydroxyurea is FDA
      approved for use in adults with sickle cell anemia to reduce the frequency of
      painful crises and the need for blood transfusions. Hydroxyurea may be given to
      children and adults with sickle cell disease for an extended period of time or
      for repeated cycles of therapy. Treatment with hydroxyurea is associated with
      known side effects such as cytotoxicity and myelosuppression, and hydroxyurea is
      genotoxic (can damage DNA). CERHR selected hydroxyurea for evaluation because of:
      its increasing use for treatment of sickle cell disease in children and adults,
      knowledge that it inhibits DNA synthesis and is cytotoxic, and published evidence
      of reproductive and developmental toxicity in rodents. The results of this
      evaluation are published in the NTP-CERHR Monograph on Hydroxyurea, which
      includes the NTP Brief and Expert Panel Report on the Reproductive and
      Developmental Toxicity of Hydroxyurea. Additional information related to the
      evaluation process, including public comments received on the draft NTP Brief and
      the final expert panel report, are available on the CERHR website (http://
      cerhr.niehs.nih.gov/). See hydroxyurea under "CERHR Chemicals" on the homepage or
      go directly to http://cerhr.niehs.nih.gov/chemicals/hydroxyurea/hydroxyurea
      eval.html). The NTP reached the following conclusions on the possible effects of
      exposure to hydroxyurea on human reproduction or development. The possible levels
      of concern, from lowest to highest, are negligible concern, minimal concern, some
      concern, concern, and serious concern. The NTP expresses serious concern that
      exposure of men to therapeutic doses of hydroxyurea may adversely affect sperm
      production. This level of concern is for all males who have reached puberty. The
      NTP concurs with the Expert Panel that there is concern that exposure of pregnant
      women to hydroxyurea may result in birth defects, abnormalities of fetal growth,
      or abnormal postnatal development in offspring. The NTP concurs with the Expert
      Panel that there is minimal concern that exposure of children to therapeutic
      doses of hydroxyurea at 5 -15 years of age will adversely affect growth. NTP will
      transmit the NTP-CERHR Monograph on the Potential Human Reproductive and
      Developmental Effects of Hydroxyurea to federal and state agencies, interested
      parties, and the public and make it available in electronic PDF format on the
      CERHR web site (http://cerhr niehs nih gov) and in printed text or CD from CERHR.

PMID- 19407859
TI  - NTP-CERHR monograph on the potential human reproductive and developmental effects
      of bisphenol A.
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for bisphenol A to
      cause adverse effects on reproduction and development in humans. The CERHR Expert
      Panel on Bisphenol A completed its evaluation in August 2007. CERHR selected
      bisphenol A for evaluation because of the: widespread human exposure; public
      concern for possible health effects from human exposures; high production volume;
      evidence of reproductive and developmental toxicity in laboratory animal studies
      Bisphenol A (CAS RN: 80-05-7) is a high production volume chemical used primarily
      in the production of polycarbonate plastics and epoxy resins. Polycarbonate
      plastics are used in some food and drink containers; the resins are used as
      lacquers to coat metal products such as food cans, bottle tops, and water supply
      pipes. To a lesser extent bisphenol A is used in the production of polyester
      resins, polysulfone resins, polyacrylate resins, and flame retardants. In
      addition, bisphenol A is used in the processing of polyvinyl chloride plastic and
      in the recycling of thermal paper. Some polymers used in dental sealants and
      tooth coatings contain bisphenol A. The primary source of exposure to bisphenol A
      for most people is assumed to occur through the diet. While air, dust, and water
      (including skin contact during bathing and swimming) are other possible sources
      of exposure, bisphenol A in food and beverages accounts for the majority of daily
      human exposure. The highest estimated daily intakes of bisphenol A in the general
      population occur in infants and children. The results of this bisphenol A
      evaluation are published in an NTP-CERHR Monograph that includes the (1) NTP
      Brief and (2) Expert Panel Report on the Reproductive and Developmental Toxicity
      of Bisphenol A. Additional information related to the evaluation process,
      including the peer review report for the NTP Brief and public comments received
      on the draft NTP Brief and the final expert panel report, are available on the
      CERHR website (http://cerhr.niehs.nih.gov/). See bisphenol A under "CERHR
      Chemicals" on the homepage or go directly to http://cerhr.niehs.
      nih.gov/chemicals/bisphenol/bisphenol.html). The NTP reached the following
      conclusions on the possible effects of exposure to bisphenol A on human
      development and reproduction. Note that the possible levels of concern, from
      lowest to highest, are negligible concern, minimal concern, some concern,
      concern, and serious concern. The NTP has some concern for effects on the brain,
      behavior, and prostate gland in fetuses, infants, and children at current human
      exposures to bisphenol A. The NTP has minimal concern for effects on the mammary
      gland and an earlier age for puberty for females in fetuses, infants, and
      children at current human exposures to bisphenol A. The NTP has negligible
      concern that exposure of pregnant women to bisphenol A will result in fetal or
      neonatal mortality, birth defects, or reduced birth weight and growth in their
      offspring. The NTP has negligible concern that exposure to bisphenol A will cause
      reproductive effects in non-occupationally exposed adults and minimal concern for
      workers exposed to higher levels in occupational settings. NTP will transmit the
      NTP-CERHR Monograph on Bisphenol A to federal and state agencies, interested
      parties, and the public and make it available in electronic PDF format on the
      CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD from CERHR.

PMID- 19407860
TI  - A geometric framework for nonlinear visual coding.
AB  - It is argued that important aspects of early and middle level visual coding may
      be understood as resulting from basic geometric processing of the visual input.
      The input is treated as a hypersurface defined by image intensity as a function
      of two spatial coordinates and time. Analytical results show how the Riemann
      curvature tensor R of this hypersurface represents speed and direction of motion.
      Moreover, the results can predict the selectivity of MT neurons for multiple
      motions and for motion in a direction along the optimal spatial orientation.
      Finally, a model based on integrated R components predicts global-motion percepts
      related to the barber-pole illusion.

PMID- 19407861
TI  - Higher-order four-wave mixing and its effect in WDM systems.
AB  - Higher-order four-wave mixing effects are evaluated in WDM systems. Calculated
      and measured results show that higher-order FWM crosstalk, though small compared
      to the first-order FWM crosstalk, could be significant in unequal channel-spacing
      WDM systems where the first-order FWM is not a problem.

PMID- 19407862
TI  - Transient glare: its effect on the lower threshold of motion.
AB  - We measured the lower threshold of motion (LTM) of suprathreshold gratings as a
      function of spatial frequency and contrast, for both transient glare and no-glare
      conditions. A two alternatives forced choice paradigm, using the method of
      constant stimuli, was adopted to measure the LTM. The LTM occurs at constant
      velocity. This velocity threshold is higher for transient glare condition than
      for no-glare condition. We found that the sudden onset of glare increases LTM
      over the whole range of contrasts. We believe the effect of transient glare
      sources on the lower threshold of motion is due to the transient loss of
      sensitivity.

PMID- 19407863
TI  - Development of thermally formed glass optics for astronomical hard X-ray
      telescopes.
AB  - The next major observational advance in hard X-ray/soft gamma-ray astrophysics
      will come with the implementation of telescopes capable of focusing 10-200 keV
      radiation. Focusing allows high signal-to-noise imaging and spectroscopic
      observations of many sources in this band for the first time. The recent
      development of depth-graded multilayer coatings has made the design of telescopes
      for this bandpass practical, however the ability to manufacture inexpensive
      substrates with appropriate surface quality and figure to achieve sub-arcminute
      performance has remained an elusive goal. In this paper, we report on new,
      thermally-formed glass micro-sheet optics capable of meeting the requirements of
      the next-generation of astronomical hard X-ray telescopes.

PMID- 19407864
TI  - Tomographic imaging of foam.
AB  - The morphology of three-dimensional foams is of interest to physicists,
      engineers, and mathematicians. It is desired to image the 3-dimensional structure
      of the foam. Many different techniques have been used to image the foam,
      including magnetic resonance imaging, and short-focal length lenses. We use a
      camera and apply tomographic algorithms to accurately image a set of bubbles. We
      correct for the distortion of a curved plexiglas container using ray-tracing.

PMID- 19407865
TI  - Propagation of polarized light in turbid media: simulated animation sequences.
AB  - A time-resolved Monte Carlo technique was used to simulate the propagation of
      polarized light in turbid media. Calculated quantities include the reflection
      Mueller matrices, the transmission Mueller matrices, and the degree of
      polarization (DOP). The effects of the polarization state of the incident light
      and of the size of scatterers on the propagation of DOP were studied. Results are
      shown in animation sequences.

PMID- 19407866
TI  - Experimental three-dimensional optical image reconstruction of heterogeneous
      turbid media from continuous-wave data.
AB  - This paper demonstrates experimental three-dimensional (3D) image reconstruction
      of optically heterogeneous turbid media from near-infrared continuous-wave
      measurements. Successful reconstruction is achieved through a full 3D finite
      element based, Newton-type reconstruction algorithm. Our experimental evidence
      shows that both absorption and scattering images of a 10x15 mm cylindrical object
      embedded in a 50x50 mm cylindrical background can be reconstructed using our
      algorithm.

PMID- 19407867
TI  - Nonlinear propagation of negatively chirped pulses: Maximizing the peak intensity
      at the output of a fiber probe.
AB  - A simple phenomenological scaling behavior is found for the power dependence of
      the pulse width for negatively pre-chirped pulses propagating in a normally
      dispersive fiber; the consequences for maximizing nonlinear signals such as two
      photon fluorescence excited at the fiber output are considered.

PMID- 19407868
TI  - Wideband squeezing in photon number fluctuations from a high-speed light-emitting
      diode.
AB  - Wideband, highly noise-suppressed squeezing was observed by using a high-speed,
      high-quantum-efficiency light-emitting diode. The squeezing bandwidth extended
      over 200 MHz. We also have investigated the dependence of the squeezing bandwidth
      on the pump-current at low temperature. The experimental result was compared with
      the theoretical predictions based on a unified model of the pump and
      recombination process and was well explained by the model at the thermionic
      emission limit.

PMID- 19407869
TI  - Intracavity stabilization of broad area lasers by structured delayed optical
      feedback.
AB  - The influence of structured delayed optical feedback (SDOF) on a broad area laser
      is investigated experimentally. SDOF is realized with a miniature-sized convex
      external mirror. The setup takes into account the small time scales involved in
      semiconductor laser dynamics by employing short external resonator lengths.
      Careful choice of the feedback parameters leads to a narrow single-lobe farfield
      even at high pump currents. The experimental results confirm earlier microscopic
      dynamic simulations by O. Hess et al. predicting that SDOF might be capable of
      stabilizing the emission of broad area lasers.

PMID- 19407870
TI  - Measurement of femtosecond Polarization Mode Dispersion (PMD) using biased p
      shifted low-coherence interferometry.
AB  - Conventional low-coherence interferometry (LCI) can be employed in the
      measurement of polarization mode dispersion (PMD) of fiber-optic components and
      fibers. However, the smallest PMD, which can be measured using this technique, is
      limited by the coherence length of the source. We propose a biased p-shifted
      Michelson interferometer where a birefringent crystal is inserted in front of the
      interferometer to introduce a bias differential group delay (DGD) larger than the
      coherence time of the source. In this way, the limitation imposed by the source
      coherence time has been overcome and PMDs much smaller than the source coherence
      time, in the order of several femtoseconds, can be measured. Experimental results
      for the PMD have been shown and compared with Jones matrix eigen-analysis. The
      theoretical model confirms the experimental observations.

PMID- 19407871
TI  - A rigorous unidirectional method for designing finite aperture diffractive
      optical elements.
AB  - We have developed a rigorous unidirectional method for designing finite-aperture
      diffractive optical elements (DOE's) that employs a micro-genetic algorithm
      (microGA) for global optimization in conjunction with a 2-D Finite-Difference
      Time-Domain (FDTD) method for rigorous electromagnetic computation. The theory
      and implementation of this microGA-FDTD design method for normally incident TE
      illumination are briefly discussed. Design examples are presented, including a
      micro-lens, a 1-to-2 beam-fanner and a 1-to-3 beam-fanner.

PMID- 19407872
TI  - Sub-Doppler resolution limited Lamb-dip spectroscopy of NO with a quantum cascade
      distributed feedback laser.
AB  - A quantum cascade distributed feedback laser operating at 5.2 microm is used to
      obtain sub-Doppler resolution limited saturation features in a Lamb-dip
      experiment on the R(13.5)1/2 and R(13.5)3/2 transitions of NO. The dips appear as
      transmission spikes with full widths of ~ 4.3 MHz. At this resolution the 73 MHz
      _-doubling of the R(13.5)3/2 line, which is normally obscured by the 130 MHz
      Doppler broadening, is easily resolved.

PMID- 19407873
TI  - Polarization correlations in pulsed, vertical cavity, surface-emitting lasers.
AB  - We have examined noise behavior and polarization correlations in the output of a
      pulsed, multitransverse-mode, vertical-cavity, surface-emitting laser (VCSEL). We
      have measured the output of the laser simultaneously in two orthogonal, linear
      polarizations as a function of drive current for pulse widths of 3 ns, 10 ns, and
      30 ns. We present joint probability distributions for the number of detected
      photoelectrons in each of the two polarization-resolved outputs. The joint
      distributions indicate that the correlations can be quite complicated, and are
      not completely described by a single number (i.e., the correlation coefficient).
      Furthermore, we find that the number of lasing modes appears to be the most
      important parameter in determining the degree of polarization correlation.

PMID- 19407874
TI  - Efficient and accurate numerical analysis of multilayer planar optical waveguides
      in lossy anisotropic media.
AB  - This paper discusses a numerical method for computing the electromagnetic modes
      supported by multilayer planar optical waveguides constructed from lossy or
      active media, having in general a diagonal permittivity tensor. The method solves
      the dispersion equations in the complex plane via the Cauchy integration method.
      It is applicable to lossless, lossy and active waveguides, and to AntiResonant
      Reflecting Optical Waveguides (ARROW's). Analytical derivatives for the
      dispersion equations are derived and presented for what is believed to be the
      first time, and a new algorithm that significantly reduces the time required to
      compute the derivatives is given. This has a double impact: improved accuracy and
      reduced computation time compared to the standard approach. A different
      integration contour, which is suitable for leaky modes is also presented.
      Comparisons are made with results found in the literature; excellent agreement is
      noted for all comparisons made.

PMID- 19407875
TI  - Widefield multiphoton and temporally decorrelated multifocal multiphoton
      microscopy.
AB  - We demonstrate a widefield multiphoton microscope and a temporally decorrelated,
      multifocal, multiphoton microscope that is based on a high-efficiency array of
      cascaded beamsplitters. Because these microscopes use ultrashort pulse excitation
      over large areas of the sample, they allow efficient use of the high-average
      power available from modern ultrashort pulse lasers.

PMID- 19407876
TI  - 4 x 10 Gb/s terrestrial optical free space transmission over 1.2 km using an EDFA
      preamplifier with 100 GHz channel spacing.
AB  - We demonstrate a transmission of 4 x 10 Gb/s WDM channels over 1.2 km of free
      space in 1.55-microm band. The transmitted beam is coupled into a single-mode
      fiber through a fiber-pigtailed collimator, which enables the use of standard 100
      GHz channel spacing and an optical preamplifier at the receiver. All the received
      channels have Q values higher than 6.

PMID- 19407877
TI  - Multi-turn all-reflective optical gyroscope.
AB  - We use calculation and simulation to characterize an all-reflective monolithic
      gyroscopic structure that supports 3 sets of orthogonal, spatially dense and
      continuous helical optical paths. This gyroscope differs from current fiber optic
      and ring laser gyroscopes primarily in the free space multi-turn nature of the
      optical path. The design also creates opportunities for introducing gain while
      minimizing spontaneous emission noise from those gain regions. The achievable
      angular measurement precision for each axis, given ideal components and no gain,
      is calculated to be ~0.001 degrees /hr for a structure of ~6.5 cm diameter, ~1
      watt average optical power, and a wavelength of 0.5 microm. For fixed power, the
      uncertainty scales as the reciprocal cube of the diameter of the structure. While
      the fabrication and implementation requirements are challenging, the needed
      reflectivities and optical surface quality have been demonstrated in more
      conventional optics. In particular, the low mass, compact character, and all
      reflective optics offer advantages for applications in space.

PMID- 19407878
TI  - Three dimensional OCT images from retina and skin.
AB  - We demonstrate the functionality of an en-face optical coherence tomography (OCT)
      system with images from the retina and skin. En-face images collected at
      different depths are subsequently used to reconstruct a 3D volume of the tissue.
      The reconstruction allows software inferred OCT longitudinal images at any
      transversal position in the stack. The position in depth in the stack before
      creating longitudinal OCT images is also adjustable, offering a valuable guidance
      tool for exploring the 3D volume of the tissue. This is illustrated by Quick time
      movies showing either depth or lateral exploration along one of two possible
      different directions in the stack of transversal OCT images. Sufficient accuracy
      of the volume rendered is obtained in 20 seconds when the system operates at 2
      frames a second. The system, equipped with the 3D rendering feature acts as a
      valuable diagnostic tool allowing "peeling off" of transversal and longitudinal
      biologic material to investigate different internal features.

PMID- 19407879
TI  - Analytical solutions for three and four diffraction orders interaction in Kerr
      media.
AB  - The analytical solution for the interaction of three diffraction orders in the
      Kerr medium is obtained by reducing the problem to the completely integrable
      Hamiltonian task. Intensities of all waves are periodic with propagation length
      and linearly related, the amplitudes are quasi-periodic and expressed in elliptic
      functions. Symmetrical four-order interaction also admits an analytical solution.

PMID- 19407880
TI  - Tomographic three-dimensional imaging of a biological specimen using wavelength
      scanning digital interference holography.
AB  - The principle of wavelength-scanning digital interference holography is applied
      to three-dimensional imaging of a small biological specimen. The images are
      reconstructed from a number of holograms digitally recorded while the wavelengths
      are varied at regular intervals, and the numerical interference of the multiple
      three-dimensional hologram fields results in tomographic images with narrow axial
      resolution. An animated three-dimensional model of the object is constructed from
      the tomographic images.

PMID- 19407881
TI  - Full cycle, low loss, low distortion phase modulation from multilayered
      dielectric stacks with terahertz optical bandwidth.
AB  - We present a customized multilayered dielectric stack employed as a broadband
      phase modulator with 6.3 THz optical bandwidth. The bandpass modulator provides
      up to a full-cycle of near-uniform phase modulation across a defined signal
      spectrum with maximized transmission and minimized pulse phase distortion. The
      modulator offers a compact, lightweight approach to active wavefront phase
      control for large optical apertures without the use of mechanical actuators. The
      modulator also provides for rapid signal switching. We contrast the narrowband
      transmission of a standard Distributed Bragg Reflector (DBR) with the broadband
      transmission of our optimized bandpass modulator. We explore techniques for
      implementing rapid phase modulation while maintaining high average signal
      transmission levels.

PMID- 19407882
TI  - Light-induced removal of 180 degrees ferroelectric domains in Rh:BaTiO3.
AB  - We show that optically-induced photorefractive space-charge fields can remove 180
      degrees ferroelectric domains in rhodium-doped barium titanate. The cross section
      of the domains must be small (less than 100 microns) for this process to occur.

PMID- 19407883
TI  - Plasmon-polariton modes guided by a metal film of finite width bounded by
      different dielectrics.
AB  - The properties of some purely bound plasmon-polariton modes guided by an
      asymmetric waveguide structure composed of a thin lossy metal film of finite
      width supported by a dielectric substrate and covered by a different dielectric
      superstrate are presented for what is believed to be the first time. The mode
      spectrum supported by these structures is quite different from the spectrum
      supported by corresponding asymmetric slab structures or similar finite-width
      symmetric waveguides. Unlike these limiting cases, the dispersion with film
      thickness exhibits an unusual oscillatory character that is explained by a
      "switching" of constituent interface modes. This mode switching is unique to
      asymmetric finite-width structures. Above a certain cut-off film thickness, the
      structure can support a long-ranging mode and its attenuation decreases very
      rapidly with decreasing film thickness, more so than the long-ranging mode in
      symmetric structures. Also, the cutoff thickness of the long-ranging mode is
      larger than the cutoff thickness of the long-ranging mode in the corresponding
      asymmetric slab waveguide, which implies that propagation along finite-width
      films is more sensitive to the asymmetry in the structure than propagation along
      a similar slab structure. Both of these results are potentially useful for the
      transmission and control of optical radiation.

PMID- 19407884
TI  - Confocal microscopy using an InGaN violet laser diode at 406nm.
AB  - We report on the application of a novel all-solid-state violet laser diode source
      to confocal microscopy. The source has the potential to replace argon ion lasers
      in a range of fluorescence based imaging systems. Improvements in system
      performance and image quality through the use of anamorphic prisms to modify the
      beam profile have been characterised. These modifications have permitted high
      quality, optically sectioned images to be obtained from laser diodes operating
      around 406nm. Living mammalian cells stained with a range of biologically
      significant fluorophores have been imaged. In addition, it has been shown that at
      this wavelength it is possible to image dyes that normally require excitation
      with UV argon laser lines.

PMID- 19407885
TI  - Increased-bandwidth in ultrashort-pulse measurement using an angle-dithered
      nonlinear-optical crystal.
AB  - We show that the usual phase-matching-bandwidth constraint in ultrashort-laser
      pulse measurement techniques is overly restrictive. Specifically, the phase
      matching bandwidth need not exceed the pulse bandwidth on every pulse. Instead,
      only the phase-matching bandwidth integrated over the measurement period need
      exceed the pulse bandwidth. We show that angle-dithering a second-harmonic
      generation crystal that is otherwise too narrowband (that is, too thick) can
      yield sufficient phase-matching bandwidth and an accurate pulse measurement. We
      apply this technique to frequency-resolved optical gating (FROG) and show that
      accurate pulse measurements can be made using a comparatively very thick and
      hence narrowband crystal. An additional advantage of using a thick crystal is
      increased signal strength.

PMID- 19407886
TI  - Coherent crosstalk impairments in polarization multiplexed transmission due to
      polarization mode dispersion.
AB  - Coherent crosstalk mechanisms induced by polarization mode dispersion in
      polarization multiplexed fiber transmission are examined by systems experiments,
      analysis and supporting modeling. Primary mechanisms include destructive
      interference, edge effects, and beat effects, leading to pulse distortion and to
      bit-error-rate penalties. Rules of thumb for tolerable crosstalk levels are
      developed.

PMID- 19407887
TI  - Quasi-phase matching of high-harmonics and attosecond pulses in modulated
      waveguides.
AB  - We describe theoretically a new technique for quasi-phase-matched generation of
      high harmonics and attosecond pulses in a gas medium, in a high ionization limit.
      A corrugated hollow-core fiber modulates the intensity of the fundamental pulse
      along the direction of propagation, resulting in a periodic modulation of the
      harmonic emission at wavelengths close to the cutoff. This leads to an increase
      of the harmonic yield of up to three orders of magnitude. At the same time the
      highest harmonics merge in a broad band that corresponds to a single attosecond
      pulse, using 15-fs driving pulses.

PMID- 19407889
TI  - Polarized infrared emissivity for a rough water surface.
AB  - The polarization state of infrared emission from water at large viewing angles is
      explained mathematically by a polarization-dependent emissivity. To provide
      polarized emissivity values for a wind-roughened water surface in a convenient
      format, this electronic paper provides interactive tables and plots of polarized
      water emissivity for the spectral range of 3-15 microm. The rough surface is
      modeled as a collection of specular facets with slopes given by a Gaussian
      distribution. The interactive electronic format provides a tutorial on emission
      polarization and it allows readers to copy the desired numbers and paste them
      into their electronic applications without the difficulty of transcribing numbers
      from printed tables.

PMID- 19407888
TI  - Dual-conjugate wavefront generation for adaptive optics.
AB  - We present results of the isoplanatic performance of an astronomical adaptive
      optics system in the laboratory, by using a dual layer turbulence simulator. We
      describe how the performance of adaptive correction degrades with off--axis
      angle. These experiments demonstrate that it is now possible to produce
      quantifiable multi-layer turbulence in the laboratory as a precursor to
      constructing multi-conjugate adaptive optics.

PMID- 19407890
TI  - Tolerancing of polarization losses in free-space optical interconnects.
AB  - A study of polarization losses in free-space optical interconnects is presented.
      A generic method is used for the prediction of optical power losses originating
      from fabrication errors in the polarization characteristics of components or
      light sources in free-space optical systems. The impact of polarization errors is
      evaluated on an individual level by a sensitivity analysis and on a system level
      by a Monte-Carlo analysis. The method is demonstrated by application to an
      optical interconnect example and validated by comparison with experimental
      results. The simultaneous interaction of multiple tolerance parameters (commonly
      known as "tolerance stackup") is shown to have a significant impact on
      polarization losses.

PMID- 19407891
TI  - Polarization properties of light backscattered from a two layer scattering
      medium.
AB  - The polarization properties of light backscattered from a two layer scattering
      medium are investigated. Linear, circular and elliptical polarization states are
      considered and it is demonstrated that the degree of polarization of the
      backscattered light is sensitive to the optical properties of both layers and to
      layer thickness. Furthermore, it is shown that the polarization memory of
      circularly polarized light enables deeper layers to be probed whereas linearly
      polarized light is more sensitive to surface layers. This has applications for
      characterizing burns and melanoma.

PMID- 19407892
TI  - Enumeration of illumination and scanning modes from real-time spatial light
      modulators.
AB  - Using a phase-only spatial light modulator (SLM) in a Fourier transform setup
      together with fast diffractive optics design algorithms provides a way to
      automatically generate complex and rapidly changing laser illumination patterns
      in the far-field. We propose a hierarchical software structure for the adaptive,
      on-line design of far-field illumination patterns. Using the on-line design
      system together with camera feedback of the illuminated scene would make it
      possible to detect and actively laser designate multiple objects in parallel.
      Possibilities for multispot, arbitrary trajectory scanning and also broad-area
      speckle-reduced illumination are demonstrated with experimentally measured
      diffraction pattern sequences from a 120 x 128 pixel phase-only SLM.

PMID- 19407893
TI  - Stabilization window and attosecond pulse train production at atom ionization in
      superintense laser field.
AB  - We present the results of numerical experiments on a two-dimensional model atom
      driven by a high-intense laser pulse. The electron wave-packet behavior is
      studied in a range of laser parameters corresponding to the dynamic stabilization
      regime. Wave packet localization in this regime with arbitrary laser
      polarizations is shown to manifest itself macroscopically by high-order harmonic
      production in the form of long trains of attosecond pulses. Calculations for the
      sub-relativistic regime of laser-atom interaction are carried out without making
      the dipole approximation in order to take into account the Lorentz force effect
      in wave packet evolution. The transition from polychotomy to the magnetic-field
      induced drifting at very high laser intensities is documented which results in
      the electron delocalization. As a consequence, the intensity dependence of the
      atomic survival probability as well as that of the efficiency of high-order
      harmonic production possess a wide "stabilization window" followed by an abrupt
      drop because of the magnetic field effect.

PMID- 19407894
TI  - Polarization Lidar: Correction of instrumental effects.
AB  - An algorithm for correcting instrumental effects in polarization lidar studies is
      discussed. Cross-talk between the perpendicular and parallel polarization
      channels and imperfect polarization of the transmitted laser beam are taken into
      account. On the basis of the Mueller formalism it is shown that - with certain
      assumptions - the combined effects of imperfect polarization of the transmitted
      laser pulse, non-ideal properties of transmitter and receiver optics and cross
      talk between parallel and perpendicular polarization channels can be described by
      a single parameter, which is essentially the overall system depolarization.

PMID- 19407895
TI  - Optimal fluorescence excitation wavelengths for detection of squamous intra
      epithelial neoplasia: results from an animal model.
AB  - Using the hamster cheek pouch carcinogenesis model, we explore which fluorescence
      excitation wavelengths are useful for the detection of neoplasia. 42 hamsters
      were treated with DMBA to induce carcinogenesis, and 20 control animals were
      treated only with mineral oil. Fluorescence excitation emission matrices were
      measured from the cheek pouches of the hamsters weekly. Results showed increased
      fluorescence near 350-370 nm and 410 nm excitation and decreased fluorescence
      near 450-470 nm excitation with neoplasia. The optimal diagnostic excitation
      wavelengths identified using this model - 350-370 nm excitation and 400-450 nm
      excitation - are similar to those identified for detection of human oral cavity
      neoplasia.

PMID- 19407896
TI  - Density measurements in a DC arcjet using scanned beam deflection tomography.
AB  - We have demonstrated a scanned beam deflection technique, and applied this
      technique to imaging the free stream of a dc arcjet plasma plume. An acousto
      optic deflector sweeps a HeNe beam transverse to the jet flow direction. A
      transform lens and split photodiode measure angular beam deflections produced by
      refractive index gradients in the arcjet plume. Line scans of beam deflection
      angle are collected at a 1 kHz sweep rate. Assuming axial symmetry, tomographic
      reconstruction is used convert the beam deflection data to refractive index.
      Multiple one-dimensional scans are stacked to produce two-dimensional refractive
      index images. Index of refraction is directly related to density for measurements
      in pure argon. Good images are obtained at chamber pressures as low as 4 Torr.
      Measurements were performed using both pure argon and argon / hydrogen / methane
      mixtures in the arcjet reactor at a variety of reactor chamber pressures
      including conditions for diamond deposition. We found significant differences in
      the radial transport with chamber pressure and with feedstock composition.
      Comparison of index of refraction data with photographs of arcjet optical
      emission shows that the emission is not a good representation of the jet density.
      The simplicity and sensitivity of the scanned beam deflection technique may allow
      its use for process control when using arcjets for plasma deposition of material.

PMID- 19407897
TI  - Introduction.
AB  - Because of its direct sensitivity to hemodymanic processes, diffuse optical
      tomography (DOT) has shown great promise as a medical imaging modality for
      problems including breast tumor detection and functional brain imaging. A key
      challenge with DOT is the extraction of useful information about the relevant
      subsurface paramaters, optical absorption and scattering parameters, from fluence
      data measures at the body surface. In this regard, DOT requires the solution of a
      generally non-linear, ill-posed inverse problem. The intent of this Focus Issue
      of Optics Express is to accomplish two tasks. First, we want to highlight the
      current state-of-the-art in DOT inverse methods. Second, the similarity of the
      DOT problem to other inverse problems prompts us to include in this issue work
      from related endeavors. The overall goals then are to broaden the views of those
      working in DOT in terms of other approaches to their problems and to make the
      wider inverse problems community more aware of this exciting new area of work.

PMID- 19407898
TI  - 3D optical tomography in the presence of void regions.
AB  - We present an investigation of the effect of a 3D non-scattering gap region on
      image reconstruction in diffuse optical tomography. The void gap is modelled by
      the Radiosity-Diffusion method and the inverse problem is solved using the
      adjoint field method. The case of a sphere with concentric spherical gap is used
      as an example.

PMID- 19407900
TI  - A shape-based reconstruction technique for DPDW data.
AB  - We give an approach for directly localizing and characterizing the properties of
      a compactly supported absorption coefficient perturbation as well as coarse scale
      structure of the background medium from a sparsely sampled, diffuse photon
      density wavefield. Our technique handles the problems of localization and
      characterization simultaneously by working directly with the data, unlike
      traditional techniques that require two stages. We model the unknowns as a
      superposition of a slowly varying perturbation on a background of unknown
      structure. Our model assumes that the anomaly is delineated from the background
      by a smooth perimeter which is modeled as a spline curve comprised of unknown
      control points. The algorithm proceeds by making small perturbations to the curve
      which are locally optimal. The result is a global, greedy-type optimization
      approach designed to enforce consistency with the data while requiring the
      solution to adhere to prior information we have concerning the likely structure
      of the anomaly. At each step, the algorithm adaptively determines the optimal
      weighting coefficients describing the characteristics of both the anomaly and the
      background. The success of our approach is illustrated in two simulation examples
      provided for a diffuse photon density wave problem arising in a bio-imaging
      application.

PMID- 19407899
TI  - Recovery of piecewise constant coefficients in optical diffusion tomography.
AB  - In optical diffusion tomography the reconstruction of the absorbtion and
      scattering coefficients is conventionally carried out in a pixel basis. The
      resulting number of unknowns makes the associated inverse problem severely ill
      posed. We have recently proposed a new approach in which the goal is to
      reconstruct boundaries of piecewise constant tissue regions as well as the
      diffusion and absorption coefficients within these regions. This method assumes
      that there is a feasible initial guess on the domain boundaries. In this paper we
      propose an extension to this approach in which the initial estimate for the
      boundary and coefficient estimation is extracted from a conventional pixel based
      reconstruction using standard image processing operations. In the computation of
      the pixel based reconstruction the output least squares problem is augmented with
      an approximated total variation prior. The performance of the proposed approach
      is evaluated using simulated frequency domain data. It is shown that since the
      total variation type approach favors domains with constant coefficients it is
      well suited for the fixing of the starting point for the actual boundary and
      coefficient reconstruction method.

PMID- 19407901
TI  - Scattering and absorption transport sensitivity functions for optical tomography.
AB  - Optical tomography is modelled as an inverse problem for the time-dependent
      linear transport equation. We decompose the linearized residual operator of the
      problem into absorption and scattering transport sensitivity functions. We show
      that the adjoint linearized residual operator has a similar physical meaning in
      optical tomography as the 'backprojection' operator in x-ray tomography. In this
      interpretation, the geometric patterns onto which the residuals are backprojected
      are given by the same absorption and scattering transport sensitivity functions
      which decompose the forward residual operator. Moreover, the 'backtransport'
      procedure, which has been introduced in an earlier paper by the author, can then
      be interpreted as an efficient scheme for 'backprojecting' all (filtered)
      residuals corresponding to one source position simultaneously into the parameter
      space by just solving one adjoint transport problem. Numerical examples of
      absorption and scattering transport sensitivity functions for various situations
      (including applications with voids) are presented.

PMID- 19407902
TI  - Evolution strategies for optical tomographic characterization of homogeneous
      media.
AB  - The reconstruction problem in diffuse optical tomography can be formulated as an
      optimization problem, in which an objective function has to be minimized. Current
      model-based iterative image reconstruction schemes commonly use information about
      the gradient of the objective function to locate the minimum. These gradient
      based search algorithms often find local minima close to an initial guess, or do
      not converge if the gradient is very small. If the initial guess is too far from
      the solution, gradient-based schemes prove inefficient for finding the global
      minimum. In this work we introduce evolution-strategy (ES) algorithms for diffuse
      optical tomography. These algorithms seek to find the global minimum and are less
      sensitive to initial guesses and regions with small gradients. We illustrate the
      fundamental concepts by comparing the performance of gradient-based schemes and
      ES algorithms in finding optical properties (absorption coefficient microa ,
      scattering coefficient micros , and anisotropy factor g) of a homogenous medium.

PMID- 19407903
TI  - Experimental and image-inversion optimization aspects of thermal-wave diffraction
      tomographic microscopy.
AB  - Thermal-wave Slice Diffraction Tomography (TSDT) is a photothermal imaging
      technique for non-destructive detection of sub-surface cross-sectional defects in
      opaque solids in the very-near-surface region (mm-mm). Conventional
      reconstructions of the well-posed propagating wave-field tomographies cannot be
      applied to the ill-posed thermal wave problem. Photothermal tomographic
      microscopy is used to collect experimental data that are numerically inverted
      with the Tikhonov regularization method to produce thermal diffusivity cross
      sectional images in materials. Multiplicity of solutions, which is inherent to
      ill-posed problems, is resolved by adopting the L-curve method for optimization.
      For tomographic imaging of sub-surface defects, a new high-resolution radiometric
      setup is constructed, which reduces the broadening of images associated with
      previous low-resolution setups.

PMID- 19407904
TI  - Analysis of the behaviour of erythrocytes in an optical trapping system.
AB  - We present a theoretical analysis of the behaviour of erythrocytes in an optical
      trapping system. We modeled erythrocyte behaviour in an optical trap by an
      algorithm which divided the cell surface into a large number of elements and
      recursively summed the force and torque on each element. We present a
      relationship between the torque and angle of orientation of the cell, showing
      that stable equilibrium orientations are at angles of 0 o , 180 o and 360 o and
      unstable equilibrium orientations are at 90 o and 270 o relative to the axis of
      beam propagation. This is consistent with our experimental observations and with
      results described in the literature. We also model behaviour of the erythrocyte
      during micromanipulation by calculating the net force on it. Such theoretical
      analysis is practical as it allows for the optimization of the optical parameters
      of a trapping system prior to performing a specific optical micromanipulation
      application, such as cell sorting or construction of a cell pattern for lab-on-a
      chip applications.

PMID- 19407905
TI  - Controlling the phase response of a diffusive wave phased array system.
AB  - Previous phased array research using anti-phase sources has shown that the phase
      response to an object scanned through a heavily scattering medium provides
      information about object position but none about size. In this paper it is
      demonstrated that controlling the relative phase between the sources enables
      different phase gradients to be set within the medium. The consequence of this is
      that the phase response is dependent on the size of an object whilst still
      maintaining localization information. Furthermore, it is demonstrated that the
      phase response can be tuned to be most sensitive to the object size under
      investigation.

PMID- 19407908
TI  - [Changes in cardiotochography following combined spinal-epidural labor
      analgesia].

PMID- 19407909
TI  - [Immunophenotype and evolution of breast carcinomas: a comparison between very
      young and postmenopausal women].
AB  - PURPOSE: The objective of this study was to evaluate the clinical, pathological
      and molecular characteristics in very young women and postmenopausal women with
      breast cancer. METHODS: We selected 106 cases of breast cancer of very young
      women (<35 years) and 130 cases of postmenopausal women. We evaluated clinical
      characteristics of patients (age at diagnosis, ethnic group, family history of
      breast cancer, staging, presence of distant metastases, overall and disease-free
      survival), pathological characteristics of tumors (tumor size, histological type
      and grade, axillary lymph nodes status) and expression of molecular markers
      (hormone receptors, HER2, p53, p63, cytokeratins 5 and 14, and EGFR), using
      immunohistochemistry and tissue microarray. RESULTS: When comparing
      clinicopathologic variables between the age groups, younger women demonstrated
      greater frequency of nulliparity (p=0.03), larger tumors (p<0.000), higher stage
      disease (p=0.01), lymph node positivity (p=0.001), and higher grade tumors
      (p=0.004). Most of the young patients received chemotherapy (90.8%) and
      radiotherapy (85.2%) and less tamoxifen therapy (31.5%) comparing with
      postmenopausal women. Lower estrogen receptor positivity 49.1% (p=0.01) and
      higher HER2 overexpression 28.7% (p=0.03) were observed in young women. In 32
      young patients (29.6%) and in 20% of the posmenopausal women, the breast
      carcinomas were of the triple-negative phenotype (p=0.034). In 16 young women
      (50%) and in 10 postmenopausal women (7.7%), the tumors expressed positivity for
      cytokeratin 5 and/or 14, basal phenotype (p=0.064). Systemic metastases were
      detected in 55.3% of the young women and in 39.2% of the postmenopausal women.
      Breast cancer overall survival and disease-free survival in five years were,
      respectively, 63 and 39% for young women and 75 and 67% for postmenopausal women.
      CONCLUSIONS: Breast cancer arising in very young women showed negative
      clinicobiological characteristics and more aggressive tumors.

PMID- 19407910
TI  - [Quality of life and sexuality of women treated for breast cancer].
AB  - PURPOSE: To evaluate the quality of life and sexuality features of women with
      breast cancer, according to the type of surgery they underwent and their
      sociodemographic characteristics. METHODS: Transversal study with 110 women
      treated for breast cancer, for at least one year in the Centro de Atencao
      Integral a Saude da Mulher of UNICAMP. The quality of life was assessed by the
      WHOQOL-bref questionnaire, and the issues on sexuality, by a specific
      questionnaire in which Cronbach's Alpha coefficient was used to validate the
      concordance of responses (alpha=0.72) and the technique of factor analysis, with
      the criterion of self value and variance maximum rotation, resulting in two
      components: intrinsic or intimacy ( how the woman sees herself sexually) and
      extrinsic or attractiveness (how the woman believes the others see her sexually).
      Sociodemographic variables have been assessed according to the WHO questionnaire,
      and the sexuality components, through the Kruskal-Wallis followed by the Mann
      Whitney's test and Spearman correlation test. RESULTS: Age, schooling, type of
      surgery and lapse of time from the surgery did not influence the quality of life
      concerning physical, environmental, and psychological aspects, as well as the
      social relationships. Women with a stable marital relationship got higher scores
      in the psychological area (p=0.04) and in the area of social relationships
      (p=0.02). Higher socioeconomic level influenced the quality of life concerning
      physical appearance (p=0.01) and environment (p=0.002). Regarding the sexuality,
      age had influence in the extrinsic component (p=0.0158). Women with a stable
      marital relationship had higher scores of quality of life in both components of
      sexuality. Higher schooling influenced in a positive way the intrinsic factor.
      Women submitted to quadrantectomy or mastectomy with immediate breast
      reconstruction showed higher scores relating to attractiveness in comparison to
      mastectomized women without reconstruction. CONCLUSIONS: Better socioeconomic
      level and better schooling, stable marital relationship and surgery with breast
      conservation are linked to better rates of quality of life, including sexuality.

PMID- 19407911
TI  - [Chromosomal abnormalities in couples with history of recurrent abortion].
AB  - PURPOSE: To asses the prevalence and clinical characteristics of couples with
      history of recurrent spontaneous abortion and chromosome abnormality, attended at
      the present service. METHODS: All the couples referred to our service due to
      history of recurrent spontaneous abortion, from January 1975 to June 2008, were
      evaluated. Only the ones whose chromosome karyotype analysis by GTG bands has
      been successfully made were included in the study. Clinical data on their age, as
      well as on the number of abortions, stillbirth, multiple malformations, livebirth
      per couple, and the result of the karyotype exam were collected. Fisher's exact
      test (p<0.05) has been used to compare the incidence of chromosome alterations
      found in our study, with data in the literature. RESULTS: There were 108 couples
      in the sample. Their ages varied from 21 to 58 years old among the men (average
      of 31.4 years old), and from 19 to 43 among the women (average of 29.9 years
      old). In ten couples, one of the mates (9.3%) presented chromosome alterations,
      which corresponded respectively to three cases (30%) of reciprocal translocation
      [two of t(5;6) and one of t(2;13)], two (20%) of Robertsonian translocation [two
      of der(13;14) and one of der(13;15)], five(50%) of mosaicism (mos) [two cases of
      mos 45,X/46,XX, one of mos 46,XX/47,XXX, one of mos 46,XY/47,XXY and one of mos
      46,XY/47,XYY] and one (10%) of chromosome inversion [inv(10)]. In one of the
      couples, the female presented two concomitant alterations: t(2;13) and
      der(13;14). Chromosome abnormalities were found in 5% of the couples with a
      history of two abortions, in 10.3% with three abortions, and in 14.3% with four
      or more abortions. CONCLUSIONS: The incidence of chromosome abnormalities seen in
      our study (9.3%) was similar to most of the studies carried out in the last 20
      years, varying from 4.8 to 10.8%. Nevertheless the high percentage of patients
      with mosaicism in our sample, has called our attention. It is believed that this
      fact may be associated to the high number of metaphases ordinarily analyzed in
      the present service.

PMID- 19407912
TI  - [Factors leading to delay in obtaining definitive diagnosis of suspicious lesions
      for breast cancer in a dedicated health unit in Rio de Janeiro].
AB  - PURPOSE: To evaluate the factors leading to delays in obtaining definitive
      diagnosis of suspicious lesions for breast cancer. METHODS: A cross-sectional,
      observational study was carried out with 104 women attending a cancer hospital
      with a diagnosis or suspected diagnosis of breast cancer. A semistructured
      questionnaire on the patients' demographic, clinical characteristics and the use
      of services was applied.Variables were compared using t-Student test, Mann
      Whitney test, Pearson's chi2 test or Fisher's exact test, as appropriate. In
      order to identify the variables associated with delays in breast cancer
      diagnosis, the Odds Ratio (OR) were calculated together with their respective 95%
      confidence intervals (95%CI) and a logistic regression model was constructed.
      RESULTS: Age of patients was 54+/-12.6 years (mean+/-standard deviation). Most of
      the women were white (48.1%), married (63.5%), living in the city of Rio de
      Janeiro (57.7%) and poorly educated (60.6%). The median time between the first
      sign or symptom of the disease and first consultation was one month and the mean
      time between first consultation and confirmation of diagnosis was 6.5 months. In
      51% of the women, diagnosis was late (stages II-IV). Symptomatic presentation and
      longer delay between symptom onset and the first evaluation and between symptom
      onset and the diagnosis were found to be significant factors (p<0.05) for delays
      in obtaining definitive diagnosis of suspicious lesions. CONCLUSIONS: The results
      of this study suggest that efforts must be made to reduce the time needed to get
      an appointment with a doctor and to confirm a diagnosis of suspicious lesions, as
      well as to educate physicians and the women themselves regarding the importance
      of breast symptoms and the value of prompt evaluation, diagnosis, and treatment.

PMID- 19407914
TI  - [The macrophages in the placenta during labor].
AB  - PURPOSE: to verify the amount of CD68+ cells in chorionic villosities in
      placentae from gestations submitted or not to labor. METHODS: transversal study
      with healthy near-term pregnant women, among whose placentae, 31 have been
      examined by immunohistochemical technique. Twenty placentae were obtained after
      vaginal delivery (VAGG) and eleven after elective cesarean sections (CESG).
      Slides were prepared with chorionic villosities samples and labeled with anti
      CD68 antibody, specific for macrophages. Labeled and nonlabeled cells were
      counted inside the villosities. Non-parametric statistical tests were used for
      the analysis. RESULTS: among the 6,424 cells counted in the villosities' stroma
      from the 31 placentae, 1,135 cells (17.6%) were stained by the CD68+. The mean of
      cells labeled by the anti-CD68 was 22+/-18 for the VAGG group and 20+/-16 for the
      CESG, in each placentary sample. CONCLUSIONS: there were no significant
      differences in the percentage of macrophages (CD68+) in association with labor.

PMID- 19407913
TI  - [Effect of magnesium sulfate on pulsatility index of uterine, umbilical and fetal
      middle cerebral arteries according to the persistence of bilateral diastolic
      notch of uterine arteries in patients with severe preeclampsia].
AB  - PURPOSE: To evaluate the effect of magnesium sulphate on the pulsatility index
      (PI) of the uterine, umbilical and fetal middle cerebral arteries, according to
      the persistency or not of the bilateral protodiastolic notch of the uterine
      arteries in severe pre-eclampsia. METHODS: A cohort study including 40 pregnant
      women with severe pre-eclampsia, 23 of them presenting bilateral protodiastolic
      notch, and 17, unilateral/absent notch. The patients were submitted to Doppler
      velocimetry before and 20 minutes after the intravenous administration of 6 g of
      magnesium sulphate. The examination was carried out with the patient in semi
      Fowler position, the sonograms being obtained during fetal inactivity, in apnea
      and absent uterine contraction periods. All the exams were performed by two
      researchers, the average being considered as the final result. Wilcoxon's test
      was used to compare the PI, before and after magnesium sulphate in both groups.
      The difference between the two measurements (before and after magnesium sulphate)
      was compared between the groups (bilateral incision and unilateral/absent
      incision) using the Mann-Whitney test. RESULTS: There was a significant increase
      in the maternal heart rate (MHR) and decrease in the maternal blood pressure, and
      in the PI medians of the two uterine arteries and in the fetal middle cerebral
      artery, after magnesium sulphate in both groups. There was a significant decrease
      in the PI of the left uterine artery and in the umbilical artery, only in the
      protodiastolic unilateral/absent notch group. Nevertheless, it was not found any
      significant difference regarding the PI of the right uterine artery, or the
      cerebral/umbilical relationship, before and after magnesium sulphate in each
      group. No difference between the groups was found, before and after magnesium
      sulphate, for any of the studied outcomes. CONCLUSIONS: After the intravenous
      administration of 6 g of magnesium sulphate to patients with severe pre
      eclampsia, a decrease in blood pressure and in the PI of the uterine, umbilical
      and fetal middle cerebral arteries occurs, besides the increase in the MHR, not
      influenced by the presence of bilateral protodiastolic notch in the uterine
      arteries.

PMID- 19407915
TI  - [Hydatidiform mole and gestational trophoblastic disease].
AB  - The hydatiform mole is a relatively rare pregnancy complication, but with
      potential to evolve to forms which need systemic treatment and can be a threat to
      life. There are two histopathological and clinical entities under the name of
      hydatiform mole: the partial and the complete mole. The differences between the
      two forms are important due to risk of evolution to persistent forms, which is
      higher for the complete moles. The diagnosis, treatment and follow-up of
      hydatiform mole have been under important changes in the last years. The number
      of asymptomatic patients has increased, due to the use of ultrasonography at the
      onset of pregnancy. The use of medication that induces uterine contractions must
      be avoided, and vacuum aspiration should be used. Soon after emptying the mole, a
      hormonal contraceptive method should be prescribed. Follow-up should be based on
      weekly serial dosages of chorionic gonadotropin. It is important that the method
      employed detects all the forms of chorionic gonadotropins (intact molecule, with
      hyper glycol, free beta subunit, and central fragment beta subunit).

PMID- 19407916
TI  - Patient-level pooled analysis of the effect of tiotropium on COPD exacerbations
      and related hospitalisations.
AB  - AIM: To assess the effect of tiotropium 18 mcg once daily on chronic obstructive
      pulmonary disease (COPD) exacerbations and exacerbation-related hospitalisations
      using a patient-level pooled analysis. METHODS: All completed randomised, placebo
      controlled, parallel-group tiotropium trials with a duration of >or=24 weeks were
      included (n=9). An exacerbation was defined in each study as >or=2 respiratory
      symptoms lasting >or=3 days, and requiring treatment with antibiotics and/or
      systemic steroids and/or hospitalisation. RESULTS: Compared with placebo (2,862
      patients), tiotropium (3,309 patients) significantly reduced by 21% both the risk
      of COPD exacerbation (95% confidence interval [CI] 0.73-0.86; p<0.0001) and the
      risk of exacerbation-associated hospitalisation (95% CI 0.65-0.96; p=0.015). Time
      to first exacerbation and first associated hospitalisation were increased. The
      protective effect of tiotropium was consistent regardless of age, gender, inhaled
      corticosteroid use and disease severity. CONCLUSION: This analysis provides
      further confirmatory evidence that tiotropium reduces the risk of exacerbation
      and associated hospitalisation.

PMID- 19407917
TI  - The prevalence of asthma in patients with obstructive sleep apnoea.
AB  - BACKGROUND: Most of the studies that have explored the relationship between
      obstructive sleep apnoea (OSA) and asthma have focused on the prevalence of
      snoring and OSA symptoms in patients with asthma. OBJECTIVES: This study was
      conducted to measure the reverse relationship - the prevalence of asthma in
      patients with diagnosed OSA. METHODS: We assessed the prevalence of asthma in all
      patients diagnosed polysomnographically to have OSA during the study period. A
      logistic regression model was developed to assess the predictors for asthma in
      patients with OSA. RESULTS: Six-hundred-and-six patients with OSA with a mean age
      of 40+/-14.5 yr (66.7% males) were included. Asthma was present in 213 OSA
      patients - a prevalence of 35.1%. Body mass index (>35 kg/m2) was the only
      predictor of asthma. CONCLUSIONS: Physicians should keep in mind the link between
      OSA and asthma. When one of these disorders is diagnosed, clinicians should
      consider the possible presence of the other.

PMID- 19407918
TI  - How often does spirometry testing induce cardiac arrhythmias?
AB  - AIMS: To describe the frequency and type of arrhythmia induced by forced
      expiratory and inspiratory flow-volume loop manoeuvres. METHODS: 735 subjects
      (548 men) aged from 10 to 98 years old (mean 54 years, SD +/- 15) were submitted
      to a conventional medical examination and spirometry testing prior to a maximal
      cardiopulmonary exercise test (CPET). A continuous digital electrocardiogram
      (ECG) was recorded during spirometry and CPET, and later reviewed and interpreted
      by the same physician (who supervised all the procedures). RESULTS: 470 subjects
      (64%) had cardiac arrhythmias during one or both procedures. About 60% of the
      arrhythmias were supraventricular, but 35 subjects (5%) presented more complex
      arrhythmias including frequent premature ventricular beats (n=31) or non
      sustained ventricular tachycardia (n=4). While arrhythmias were more often
      exposed by the CPET (p<0.01), in 68 cases (10% of the total sample) arrhythmias
      were only induced by spirometry; these included four cases of non-sustained
      supraventricular tachycardia (n=4). CONCLUSIONS: Spirometry is a safe procedure
      with regard to induction of cardiac arrhythmias. Spirometry-induced arrhythmias
      tend to be simple and were always short-lasting. In some cases, ECG recording
      during spirometry showed arrhythmias that would not be induced by a progressive
      maximal exercise test.

PMID- 19407919
TI  - Martial arts fall training to prevent hip fractures in the elderly.
AB  - Hip fractures are a common and serious consequence of falls. Training of proper
      fall techniques may be useful to prevent hip fractures in the elderly. The
      results suggested that martial arts fall techniques may be trainable in older
      individuals. Better performance resulted in a reduced impact force. INTRODUCTION:
      Hip fractures are a common and serious consequence of falls. Fall training may be
      useful to prevent hip fractures in the elderly. This pilot study determined
      whether older individuals could learn martial arts (MA) fall techniques and
      whether this resulted in a reduced hip impact force during a sideways fall.
      METHODS: Six male and nineteen female healthy older individuals completed a five
      session MA fall training. Before and after training, force and kinematic data
      were collected during volitional sideways falls from kneeling position. Two MA
      experts evaluated the fall performance. Fear of falling was measured with a
      visual analog scale (VAS). RESULTS: After fall training, fall performance from a
      kneeling position was improved by a mean increase of 1.6 on a ten-point scale (P
      < 0.001). Hip impact force was reduced by a mean of 8% (0.20 N/N, P = 0.016).
      Fear of falling was reduced by 0.88 on a VAS scale (P = 0.005). CONCLUSION: MA
      techniques may be trainable in older individuals, and a better performance may
      reduce the hip impact force in a volitional sideways fall from a kneeling
      position. The additional reduction of fear of falling might result in the
      prevention of falls and related injuries.

PMID- 19407920
TI  - Isokinetic resistance training increases tibial bending stiffness in young women.
AB  - Bone mineral content (BMC) and bone mineral density (BMD) are common but
      imperfect surrogate measures of bone strength. The mechanical response tissue
      analyzer is a device that measures long bone bending stiffness (EI), which
      strongly predicts bone breaking strength. We hypothesized that isokinetic
      resistance training of the knee flexor and extensor muscles would increase tibial
      EI, BMC, and BMD in young women. Fifty-two women, aged 18-26 years, performed
      concentric (CON, n = 30) or eccentric (ECC, n = 22) isokinetic resistance
      training with the nondominant leg three times per week for 20 weeks. Before and
      after the training period, subjects were tested for CON and ECC peak torque of
      the knee flexor and extensor muscles with isokinetic dynamometry, tibial BMC and
      BMD using dual-energy X-ray absorptiometry, and tibial EI using mechanical
      response tissue analysis. Both training groups increased CON (15-21%) and ECC (17
      31%) peak torque vs. the untrained leg. Tibial EI increased in the entire cohort
      (26%) and in each training group (CON 34%, ECC 16%) vs. the untrained tibia.
      Tibial BMC and BMD increased in the trained and untrained tibiae, with no
      significant differences between limbs. No differential tibial EI or bone mineral
      outcomes were observed between the CON and ECC training groups. In summary, CON
      and ECC isokinetic resistance training increased tibial EI, but not BMC or BMD,
      in young women.

PMID- 19407921
TI  - The deficit of male-biased genes on the D. melanogaster X chromosome is
      expression-dependent: a consequence of dosage compensation?
AB  - In Drosophila, there is a consistent deficit of male-biased genes on the X
      chromosome. It has been suggested that male-biased genes may evolve from
      initially unbiased genes as a result of increased expression levels in males. If
      transcription rates are limited, a large increase in expression in the testis may
      be harder to achieve for single-copy X-linked genes than for autosomal genes,
      because they are already hypertranscribed due to dosage compensation. This
      hypothesis predicts that the larger the increase in expression required to make a
      male-biased gene, the lower the chance of this being achievable if it is located
      on the X chromosome. Consequently, highly expressed male-biased genes should be
      located on the X chromosome less often than lowly expressed male-biased genes.
      This pattern is observed in our analysis of publicly available data, where
      microarray data or EST data are used to detect male-biased genes in D.
      melanogaster and to measure their expression levels. This is consistent with the
      idea that limitations in transcription rates may prevent male-biased genes from
      accumulating on the X chromosome.

PMID- 19407922
TI  - Inventory and comparative evolution of the ABC superfamily in the genomes of
      Phytophthora ramorum and Phytophthora sojae.
AB  - Automated and manual annotation of the ATP binding cassette (ABC) superfamily in
      the Phytophthora ramorum and P. sojae genomes has identified 135 and 136 members,
      respectively, indicating that this family is comparable in size to the
      Arabidopsis thaliana and rice genomes, and significantly larger than that of two
      fungal pathogens, Fusarium graminearum and Magnaporthe grisea. The high level of
      synteny between these oomycete genomes extends to the ABC superfamily, where 108
      orthologues were identified by phylogenetic analysis. The largest subfamilies
      include those most often associated with multidrug resistance. The P. ramorum
      genome contains 22 multidrug resistance-associated protein (MRP) genes and 49
      pleiotropic drug resistance (PDR) genes, while P. sojae contains 20 MRP and 49
      PDR genes. Tandem duplication events in the last common ancestor appear to
      account for much of the expansion of these subfamilies. Recent duplication events
      in the PDR and ABCG families in both the P. ramorum and the P. sojae genomes
      indicate that selective expansion of ABC transporters may still be occurring. In
      other kingdoms, subfamilies define both domain arrangements and proteins having a
      common phylogenetic origin, but this is not the case for several subfamilies in
      oomycetes. At least one ABCG type transporter is derived from a PDR transporter,
      while transporters in the ABCB-half family cluster with transporters from
      bacterial, plant, and metazoan genomes. Additional examples of transporters that
      appear to be derived from horizontal transfer events from bacterial genomes
      include components of transporters associated with iron uptake and DNA repair.

PMID- 19407923
TI  - Evolution of phage-type RNA polymerases in higher plants: characterization of the
      single phage-type RNA polymerase gene from Selaginella moellendorffii.
AB  - Selaginella moellendorfii (spikemoss) sequence trace data encoding a polypeptide
      highly similar to angiosperm and moss phage-type organelle RNA polymerases
      (RpoTs) were used to isolate a BAC clone containing the full-length gene SmRpoT
      as well as the corresponding cDNA. The SmRpoT mRNA comprises 3452 nt with an open
      reading frame of 3006 nt, encoding a putative protein of 1002 amino acids with a
      molecular mass of 113 kDa. The SmRpoT gene comprises 19 exons and 18 introns,
      conserved in their position with those of the angiosperm and Physcomitrella RpoT
      genes. In phylogenetic analyses, the Selaginella RpoT polymerase is in a sister
      position to all other phage-type polymerases of angiosperms. However, according
      to its conserved exon-intron structure, the Selaginella RpoT gene is
      representative of the molecular evolutionary lineage giving rise to the RpoT gene
      family of flowering plants. The N-terminal transit peptide of SmRpoT is shown to
      confer targeting of green fluorescent protein exclusively to mitochondria after
      transient expression in Arabidopsis and Selaginella protoplasts. Angiosperms and
      the moss P. patens possess small gene families encoding RpoTs, which include
      mitochondrial- and chloroplast-targeted RNA polymerases. In striking contrast,
      the Selaginella RpoT gene is shown to be single-copy, although Selaginella, as a
      lycophyte, has a phylogenetic position between Physcomitrella and angiosperms.
      Thus, there is no evidence that Selaginella may contain a nuclear-encoded phage
      type chloroplast RNA polymerase.

PMID- 19407925
TI  - Why it's important to know Percheron's artery: solitary carotid stenosis as a
      unique cause of anterior, posterior and bithalamic ischemia.

PMID- 19407924
TI  - Investigation of heteroplasmy in the human mitochondrial DNA control region: a
      synthesis of observations from more than 5000 global population samples.
AB  - Instances of point and length heteroplasmy in the mitochondrial DNA control
      region were compiled and analyzed from over 5,000 global human population
      samples. These data represent observations from a large and broad population
      sample, representing nearly 20 global populations. As expected, length
      heteroplasmy was frequently observed in the HVI, HVII and HVIII C-stretches.
      Length heteroplasmy was also observed in the AC dinucleotide repeat region, as
      well as other locations. Point heteroplasmy was detected in approximately 6% of
      all samples, and while the vast majority of heteroplasmic samples comprised two
      molecules differing at a single position, samples exhibiting two and three mixed
      positions were also observed in this data set. In general, the sites at which
      heteroplasmy was most commonly observed correlated with reported control region
      mutational hotspots. However, for some sites, observations of heteroplasmy did
      not mirror established mutation rate data, suggesting the action of other
      mechanisms, both selective and neutral. Interestingly, these data indicate that
      the frequency of heteroplasmy differs between particular populations, perhaps
      reflecting variable mutation rates among different mtDNA lineages and/or
      artifacts of particular population groups. The results presented here contribute
      to our general understanding of mitochondrial DNA control region heteroplasmy and
      provide additional empirical information on the mechanisms contributing to mtDNA
      control region mutation and evolution.

PMID- 19407927
TI  - Metabolism and pharmacokinetics in rats of ganoderiol F, a highly cytotoxic and
      antitumor triterpene from Ganoderma lucidum.
AB  - The metabolism of ganoderiol F (GF), a cytotoxic and antitumor triterpene from
      Ganoderma lucidum, by intestinal bacteria and its pharmacokinetics in rats were
      investigated by using liquid chromatography/mass spectrometry/mass spectrometry
      (LC/MS/MS). GF was converted to ganodermatriol by anaerobic incubation with
      bacterial mixtures from rats and humans. This metabolite was detected in rat
      feces, but not in plasma and urine, after oral administration of GF. The fate of
      GF after oral (p.o.) and intravenous (i.v.) administration to rats was examined
      in pharmacokinetics studies. Plasma samples pretreated by solid-phase extraction
      were quantified by HPLC/MS/MS over a GF concentration range of 1.25-100 ng/ml
      (S/N = 5). The intra- and interday precision (CV%) was below 8% and accuracy was
      within the range of 95.9-103.6% for all samples. The range of recovery ratios was
      89.2-98.2%. After the administration of GF at 0.5 mg/kg i.v., the plasma
      concentrations of GF quickly declined and the elimination half-life values
      (t(1/2alpha) and t(1/2beta)) were about 2.4 and 34.8 min. On the other hand, the
      elimination half-life values (t(1/2alpha)) after p.o. administration of GF at
      doses of 20 and 50 mg/kg were 14.4 and 143.3 min for the former, and 18.6 and
      114.6 min for the latter. The AUC(0-t) value was 11.17 (ng/ml) h at a GF dose of
      0.5 mg/kg i.v., but 49.4 and 111.6 (ng/ml) h at GF doses of 20 and 50 mg/kg p.o.,
      respectively, indicating that the AUC(0-t) value is proportional to the
      administered oral doses. The estimated absolute bioavailability of GF in rats was
      F = 0.105.

PMID- 19407926
TI  - Detection of anti-CUEC-23 antibodies in serum of patients with esophageal
      squamous cell carcinoma: a possible new serum marker for esophageal cancer.
AB  - BACKGROUND: Serological identification of antigens by recombinant cDNA expression
      cloning (SEREX) is an established method for detecting new tumor-specific
      antigens. Antibodies to SEREX antigens may be useful for the detection of
      esophageal squamous cell carcinoma (SCC). METHODS: A phage cDNA library of a
      human esophageal SCC cell line was screened using sera of patients with
      esophageal SCC. The presence and levels of serum antibodies to SEREX antigens
      were established by Western blotting and enzyme-linked immunosorbent assay
      (ELISA) using purified recombinant antigen proteins, respectively. RESULTS: The
      newly identified esophageal SCC antigen is encoded by a novel gene located on
      chromosome 1, here designated CUEC-23. Serum CUEC-23-antibodies (s-CUEC-23-Abs)
      were detected in 14 of 54 patients with esophageal SCC (26%) by Western blot
      analysis. Esophageal SCCs were positive for s-CUEC-23-Abs together with CEA, SCC
      Ag or CYFRA21-1 in 44, 41 and 52% of cases, respectively. There was no detectable
      association between the presence of s-CUEC-23-Abs and clinicopathological
      variables. ELISA showed that the levels of s-CUEC-23-Abs were significantly
      higher in patients with esophageal SCC than in healthy volunteers (17% in the
      former using the mean+3 SD of s-CUEC-23-Abs in healthy controls as the cutoff).
      CONCLUSION: A new tumor antigen, CUEC-23, was identified by SEREX screening. s
      CUEC-23-Abs might be a useful serum marker to detect esophageal SCC.

PMID- 19407928
TI  - Detection of TT virus by single-primer sequence-independent amplification in
      multiple samples collected from an outbreak of gastroenteritis.
AB  - A panel of gastroenteritis outbreak samples was subjected to a virus purification
      and concentration algorithm followed by a sequence-independent amplification
      method devised to detect viral enteric pathogens. The application of these
      methods allowed the identification of torque teno virus (TTV) in one outbreak.
      The complete genome sequence of 3,260 nt was obtained through "genome walking",
      and four open reading frames were deduced from the genomic sequence. Phylogenetic
      analysis grouped this virus in TTV genetic group 3, clustering with genotype 27,
      with 85% similarity at the nt level with strain SAa-01.

PMID- 19407929
TI  - Comments on Schoonman et al.: Migraine headache is not associated with cerebral
      or meningeal vasodilatation: a 3 T magnetic resonance angiography study (Brain
      2008; 131:2192-2200).

PMID- 19407930
TI  - Psychological distress and mental health treatment among persons with and without
      active duty military experience, Behavioral Risk Factor Surveillance System,
      United States, 2007.
AB  - OBJECTIVES: To examine self-reported psychological distress (K-6 scale) and
      mental health treatment among persons with and without active duty U.S. military
      experience (ADME) currently residing in private residences in the U.S. METHODS:
      Analysis of 2007 Behavioral Risk Factor Surveillance System data from 35 states,
      District of Columbia, and Puerto Rico (n = 202,029 for those answering all K-6
      questions, the treatment question, and the ADME question) RESULTS: Adjusting for
      age, sex, race/ethnicity, and education, overall mean K-6 scores of those with
      and without ADME were similar (p = 0.3223); however, more of those with, vs.
      without, ADME reported current mental health treatment (11.7 % vs. 9.6 %, p =
      0.0001). Those with ADME receiving such treatment had a higher mean K-6 score
      (7.7) than those without ADME receiving such treatment (6.9) (p = 0.0032).
      CONCLUSIONS: Community-dwelling persons with ADME have similar demographically
      adjusted mean K-6 psychological distress scores, but greater likelihood of recent
      mental health treatment, compared to those without ADME.

PMID- 19407931
TI  - Incidence of hemorrhage among anticoagulated patients receiving antiplatelet
      therapy after percutaneous coronary intervention.
AB  - This study aimed to compare major hemorrhage rates among patients receiving
      warfarin, acetylsalicylic acid (ASA), and clopidogrel to those receiving ASA and
      clopidogrel following percutaneous coronary intervention with stent implantation.
      This retrospective cohort study identified patients with stents implanted between
      September 1, 2003 and December 31, 2006. Patients treated with warfarin, ASA, and
      clopidogrel within 30 days of hospital discharge (Triple Therapy group) were
      matched by age, sex, and stent type to patients treated with ASA and clopidogrel
      (Dual Therapy group). Outcomes included the incidence rates of major hemorrhage
      and major adverse coronary events (MACE) within 12 months of stent implantation.
      There were 175 and 339 patients in the Triple Therapy and Dual Therapy groups,
      respectively. There were 25 (14.3%) and 10 (3.0%) major hemorrhages in the Triple
      Therapy and Dual Therapy groups, respectively (OR 9.0; 95% CI, 3.1-26.1).
      Patients in the Triple Therapy group had a greater likelihood of MACE compared to
      patients in the Dual Therapy group (OR 2.0; 95% CI 1.1-3.8). Post-stent treatment
      with warfarin, ASA, and clopidogrel was associated with a substantially greater
      likelihood of major hemorrhage than treatment with ASA and clopidogrel alone.

PMID- 19407933
TI  - Formulation and pharmacokinetics of self-assembled rifampicin nanoparticle
      systems for pulmonary delivery.
AB  - PURPOSE: To formulate rifampicin, an anti-tuberculosis antibiotic, for aerosol
      delivery in a dry powder 'porous nanoparticle-aggregate particle' (PNAP) form
      suited for shelf stability, effective dispersibility and extended release with
      local lung and systemic drug delivery. METHODS: Rifampicin was encapsulated in
      PLGA nanoparticles by a solvent evaporation process, spray dried into PNAPs
      containing varying amounts of nanoparticles, and characterized for physical and
      aerosol properties. Pharmacokinetic studies were performed with formulations
      delivered to guinea pigs by intratracheal insufflation and compared to oral and
      intravenous delivery of rifampicin. RESULTS: The PNAP formulations possessed
      properties suitable for efficient deposition in the lungs. In vitro release
      showed an initial burst of rifampicin, with the remainder available for release
      beyond eight hours. PNAPs delivered to guinea pigs by insufflation achieved
      systemic levels of rifampicin detected for six to eight hours. Moreover,
      rifampicin concentrations remained detectable in lung tissue and cells up to and
      beyond eight hours. Conversely, after pulmonary delivery of an aerosol without
      nanoparticles, rifampicin could not be detected in the lungs at eight hours.
      CONCLUSIONS: Our results indicate that rifampicin can be formulated into an
      aggregated nanoparticle form that, once delivered to animals, achieves systemic
      exposure and extends levels of drug in the lungs.

PMID- 19407934
TI  - Cardiac troponin I and acute lung injury after subarachnoid hemorrhage.
AB  - INTRODUCTION: There are few predictors of acute lung injury (ALI) or the acute
      respiratory distress syndrome (ARDS) after subarachnoid hemorrhage (SAH). We
      hypothesized that cardiac troponin I, which is associated with cardiovascular
      morbidity, would also predict ALI. METHODS: We prospectively enrolled 171
      consecutive patients with SAH. Troponin was routinely measured on admission and
      the next day and subsequently if abnormal. We prospectively recorded the maximum
      troponin, in-hospital events, and clinical endpoints. ALI and ARDS were defined
      by standard criteria. RESULTS: Acute lung injury was found in 10 patients (6%),
      ARDS in an additional 14 (8%), and pulmonary edema without lung injury in 9 (5%).
      Maximum troponin was different in patients without lung injury or pulmonary edema
      (0.03 [0.02-0.12] mcg/l), ALI (0.17 [0.04-1.4]), or ARDS (0.31 [0.9-1.8], P <
      0.001). In ROC analysis, a cutoff of 0.04 mcg/l had 91% sensitivity and 42%
      specificity for ALI or ARDS (AUC = 0.75, P < 0.001). Troponin was associated with
      ALI or ARDS after accounting for neurologic grade in multivariate models without
      further contribution from pneumonia, packed red cell transfusion, gender, tobacco
      use, coronary artery disease, vasospasm, depressed ejection fraction on
      echocardiography, or CT grade. Lung injury was associated with worse functional
      outcome at 14 days, but not at 28 days or 3 months. CONCLUSION: Troponin I is
      associated with the development of ALI after SAH.

PMID- 19407932
TI  - Programmed cell death pathways and current antitumor targets.
AB  - Apoptosis and autophagic cell deaths are programmed cell deaths and they play
      essential roles in cell survival, growth and development and tumorigenesis. The
      huge increase of publications in both apoptosis and autophagic signaling pathways
      has contributed to the wealth of knowledge in facilitating the understanding of
      cancer pathogenesis. Deciphering the molecular pathways and molecules involved in
      these pathways has helped scientists devise and develop targeted strategies
      against cancer. Various drugs targeting the apoptotic TRAIL, Bcl-2 and proteasome
      pathways are already in Phase II/III clinical trials. The first mTOR inhibitor,
      temsirolimus has already been approved by the FDA, USA for the treatment of
      advanced renal cell carcinoma and more mTOR inhibitors are expected to be in the
      market in a few years time. Strategizing against aberrant autophagy activities in
      various cancers by using either pro-autophagics or autophagy inhibitors are
      currently been investigated. This review aims to discuss the most recent
      antitumor strategies targeting the apoptosis and autophagy signaling pathways and
      the latest outcome of clinical trials of the above drugs.

PMID- 19407935
TI  - Sixty day continuous use of subdermal wire electrodes for EEG monitoring during
      treatment of status epilepticus.
AB  - INTRODUCTION: Use of continuous EEG in the ICU setting is increasing. The EEG
      electrode continues to be a weak link in the chain from recording to
      interpretation. The technical difficulties of maintaining artifact-free, low
      impedance data collection are magnified by the ICU environment and prolonged
      duration of monitoring often required for these patients. CASE: We describe a
      case demonstrating the longest reported continuous use of subdermal wire
      electrodes. DISCUSSION: Subdermal wire electrodes offer a safe method to overcome
      technical challenges while maintaining high-recording quality. Their advantages
      and disadvantages are considered in specific circumstances and in comparison to
      other electrode types.

PMID- 19407936
TI  - Choice of radiotherapy planning modality influences toxicity in the treatment of
      locally advanced esophageal cancer.
AB  - PURPOSE: Three-dimensional computed tomography-based radiotherapy planning
      (3DCTP) is increasingly employed in the treatment of esophageal cancer. It is
      unknown whether a 3DCTP approach influences outcomes compared to two-dimensional
      planning (2DP). This study compares clinical outcomes for homogeneously treated
      patient cohorts stratified by planning modality. METHODS AND MATERIALS: A
      retrospective chart review was conducted on patients with T3/4 and/or node
      positive esophageal carcinoma treated at the Cleveland Clinic between July 1,
      2003 and May 31, 2006 who were managed with an institutional regimen consisting
      of preoperative radiotherapy, whether 3DCTP or 2DP [30 Gy/20 fractions/1.5 Gy
      twice daily over 2 weeks], with concurrent cisplatin and 5-fluorouracil the first
      week. Following definitive resection, an identical postoperative course of
      concurrent chemoradiotherapy (CRT) was delivered. RESULTS: One hundred and forty
      one patients completed preoperative CRT and were available for review. The median
      follow-up of living patients is 21.7 months. Fifty-five percent underwent 3DCTP
      and 45% had 2DP. The treatment groups were similar, with the exception of
      clinical stage group, with 2DP having more stage II and fewer stage III patients
      than 3DCTP (p = 0.02). 3DCTP plans had significantly smaller field sizes by area
      (p < 0.0001). Pathologic response, locoregional control, distant control, and
      overall survival were equivalent between the two planning modalities. Esophagitis
      was significantly less common with a 3D approach compared to 2D planning (49% vs.
      71%, p = 0.0096), with other toxicities equivalent between the groups.
      CONCLUSIONS: 3DCTP reduces acute esophagitis in patients receiving multimodality
      therapy for esophageal cancer without compromising clinical outcomes.

PMID- 19407937
TI  - [Information on the policies of the Medical Devices Safety Act].

PMID- 19407938
TI  - [Public health ethics in general practice].

PMID- 19407940
TI  - [Communications by the Blood Working Group of the Federal Public Health
      Administration. Measures to prevent transfusion-induced lung failure (TRALI)].

PMID- 19407941
TI  - Thinking and strategy on the diagnosis and treatment of functional
      gastrointestinal disorders with integrative medicine.

PMID- 19407942
TI  - Foundation and clinical research on the effect of traditional Chinese herbs on
      gastrointestinal motility.

PMID- 19407943
TI  - Discussion on certain issues of the diagnosis and treatment of functional
      constipation.

PMID- 19407944
TI  - Traditional Chinese medicine clinical experience of the treatment for irritable
      bowel syndrome.

PMID- 19407945
TI  - Evaluation by survival analysis on effect of traditional Chinese medicine in
      treating children with respiratory syncytial viral pneumonia of phlegm-heat
      blocking Fei syndrome.
AB  - OBJECTIVE: To objectively evaluate the clinical effect of traditional Chinese
      medicine in treating children's respiratory syncytial viral pneumonia (RSVP) of
      phlegm-heat blocking Fei syndrome (PHBFS). METHODS: A single-blinded multi
      center, blocked, randomized and parallel-controlled method was adopted. The
      clinical study was carried out on 206 children with RSVP-PHBFS who were assigned
      to two groups, 108 in the test group treated through intravenous dripping of
      Qingkailing Injection () in combination of oral intake of Er'tong Qingfei Oral
      Liquid () and 98 in the control group with intravenous dripping of ribavirin
      injection in combination with oral intake of potassium guaiacol sulfonate oral
      liquid, all for 10 days. The clinical efficacy was evaluated and compared at the
      end of the trial from various aspects by three methods including comprehensive
      efficacy, post-treatment main symptoms score difference and survival analysis of
      the main symptoms. RESULTS: After treatment, in the test group, 60 patients were
      cured, 36 markedly alleviated, and 12 improved. In the control group, 41 were
      cured, 38 markedly alleviated, 18 improved and 1 unchanged. Comparison on the
      comprehensive efficacy between the two groups shows a better efficacy in the test
      group (chi(2)=4.4527, P=0.0348). Scores of the main symptoms were lowered after
      treatment in both groups, the difference was 22.41+/-4.99 scores in the test
      group and 17.61+/-6.34 scores in the control group, being more significant in the
      former (t=-5.99, P<0.01). Survival analysis shows that there was significant
      difference between the two groups in the effect initiating time on such symptoms
      as fever, cough, copious sputum, shortness of breath, and rales, which was
      earlier in the test group (P<0.01 or P<0.05). CONCLUSION: Evaluation of the
      efficacy of traditional Chinese medicine in treating children with RSVP-PHBFS by
      using the three methods jointly could better show the objectivity of the
      evaluation.

PMID- 19407946
TI  - Differential gene expression profiles in coronary heart disease patients of blood
      stasis syndrome in traditional Chinese medicine and clinical role of target gene.
AB  - OBJECTIVE: To investigate the differential gene expression profiles in coronary
      heart disease (CHD) patients of blood-stasis syndrome (BSS) by oligonucleotide
      microarray technique, and the clinical significance of target gene. METHODS:
      Subjects were assigned to CHD patients with BSS (n=8), CHD patients without BSS
      (n=8), and BSS patients without CHD (n=8) based on coronary angiography and the
      diagnostic criteria of BSS. The sex- and age-matched healthy volunteers (n=8)
      were enrolled as the control group. Venous blood samples were collected for RNA
      extraction; Test-3 chip was employed to examine the quality of samples. Then, the
      samples were hybridized with Affymetrix U133 Plus 2.0 array to compare the gene
      expression profiles among the four groups. Gene-array scanner and gene chip
      operating software were applied to screen out hybridization signals and analyze
      gene expression, respectively. Based on the comparison of the samples of the four
      groups, the differential genes related with CHD and BSS were analyzed with Gene
      Ontology (GO) and pathway, and target genes selected were confirmed by real-time
      reverse transcription polymerase chain reaction (RT-PCR). Thirty CHD patients
      with BSS were selected according to the former criteria and 40 healthy as
      controls. The serum concentration of interleukin-8 (IL-8) was determined by
      double-antibody sandwich avidin-biotin peroxidase complex enzyme-linked (ABC
      ELISA). RESULTS: A total of 107 differential genes were found being associated
      with CHD, including 48 up-regulated genes and 59 down-regulated genes. Among
      these 107 differential genes, 14 genes (13.1%) were found related to inflammatory
      reaction and immune response through GO analysis. In the pathway analysis, 4 of
      15 conspicuous pathways were referred to the inflammation and immune response.
      Among 48 differential genes related to BSS, 26 genes were up-regulated, and 22
      were down-regulated. Five of the 48 genes (10.4%) and 5 of 10 significant
      pathways were involved in inflammation and immunity. The results of real-time RT
      PCR proved the accuracy of the gene chip. The patients have markedly higher level
      of serum IL-8 compared to the controls (P<0.05). CONCLUSION: The correlation of
      inflammatory- and immune-related genes with CHD patients of BSS was revealed at
      the level of nucleic acid, and the target gene IL-8 may play a role in the
      pathobiology of CHD with BSS.

PMID- 19407947
TI  - Clinical observation on treatment of colonic cancer with combined treatment of
      chemotherapy and Chinese herbal medicine.
AB  - OBJECTIVE: To observe the clinical effect of combined chemotherapy and Chinese
      herbal medicine in treating colonic cancer. METHODS: One hundred and sixty-three
      patients were assigned, according to their will, to two groups, 105 in the
      traditional Chinese medicine treated group (Group A) and 58 in the combined
      treatment group (Group B). The Chinese herbal drug Zhao's Weitiao No. 3 ( 3, ZW3)
      was given to both groups, twice a day, 40 mL each time, 30 days as one cycle, and
      over 6 cycles applied in total. For patients in Group B, the chemotherapy of OLF
      protocol (L-OHP+LV+5-FU) was given for 4-6 cycles. The effects of treatment on
      the main symptoms, tumor mass, patients' quality of life (QOL) and body weight,
      changes of carcino-embryonic antigen (CEA), as well as the integral effect and
      survival rate were observed and compared. RESULTS: The total effective rate in
      Group A and Group B was 89.52% and 86.21% respectively, on the main clinical
      symptoms; 86.67% and 93.10% on tumor mass, 82.86% and 77.59% on QOL, 85.71% and
      75.86% on body weight and 76.19% and 79.31% on CEA. The integral efficacy of
      total beneficial rate was 73.33% and 68.97%; and the 3-year survival rate 49.52%
      and 46.65% in Group A and Group B. These data showed that the effect in Group A
      was better than in Group B in terms of clinical symptom improvement, QOL, body
      weight and integral beneficence increase and survival rate, though it was
      inferior in reducing the tumor mass and CEA level. CONCLUSION: Chinese drug ZW3
      for the treatment of colonic cancer could improve the main clinical symptoms,
      improve the QOL, increase body weight and prolong the survival time of patients,
      showing a favorable integral effect.

PMID- 19407948
TI  - Study of the relationship between carotid intima-media thickness and traditional
      Chinese medicine syndrome of dyslipidemia.
AB  - OBJECTIVE: The study aimed to explore the relationship between the carotid intima
      media thickness (IMT), lipids, high-sensitivity C-reactive protein (hs-CRP),
      homocysteine (Hcy) and other indices of laboratory and the traditional Chinese
      medicine (TCM) syndrome of dyslipidemia. METHODS: A total of 152 dyslipidemia
      patients and 8 healthy people (taken as the control group) were recruited.
      According to the theory of the TCM syndrome, 152 dyslipidemia patients were
      assigned to 4 groups: the stagnation of phlegm (SP) group, the blood stasis
      blocking channels (BSBC) group, the stagnation of phlegm and blood (SPB) group
      and the non-stagnation of phlegm and blood (NSPB) group. The carotid ultrasonic
      test, hs-CRP, Hcy, blood rheology and blood lipids were examined for all the
      recruited patients. The relationships among carotid IMT, laboratory indices and
      TCM syndrome of dyslipidemia were analyzed by the methods of F test and multiple
      linear regressions. RESULTS: (1) Carotid IMT was significantly different among
      groups of healthy people and different TCM syndromes. The sequence from lowest to
      highest was: healthy group, NSPB group, SP group, SPB group and BSBC group. (2)
      Triglyceride (TG) and blood rheology were significantly different between the
      groups of healthy people and different TCM syndromes. Among different TCM
      syndrome groups, TG and blood rheology in the NSPB group were the lowest, but
      were the highest in SPB group. (3) Hcy, very low density lipoprotein and TG were
      correlated with atherosclerosis of the carotid. CONCLUSION: Carotid IMT, TG and
      blood rheology were closely correlated with the TCM syndrome of dyslipidemia.
      Atherosclerosis of the carotids would be prone to occur if one of these factors
      was heightened.

PMID- 19407949
TI  - Clinical observation on the treatment of post-cesarean hypogalactia by auricular
      points sticking-pressing.
AB  - OBJECTIVE: To explore the effect of auricular points sticking-pressing (APSP) in
      treating post-cesarean hypogalactia (PCH). METHODS: A randomized, controlled,
      single-blinded clinical trial on 116 patients with PCH was carried out. They were
      equally assigned to the treatment group and the control group. The treatment
      group received APSP, with the pellets pressed for 4 times daily, while the
      control group was only asked to do lactation to meet infant demand. The
      therapeutic efficacy and the changes in scores of traditional Chinese medicine
      (TCM) syndrome, volume of milk secretion, supplementary feeding and serum level
      of prolactin (PRL) in the two groups were estimated and compared after the
      patients had been treated for 5 days. RESULTS: The cured and markedly effective
      rate in the treatment group was 89.7%, which was significantly higher than that
      in the control group (27.6%, P<0.05), 95% CI (0.1543, 0.2527). The improvement of
      TCM syndrome, elevation of milking volume, decrease of the supplementary feeding
      and increase of PRL level revealed in the treatment group were all superior to
      those in the control group, showing statistical significance (P<0.01).
      CONCLUSION: APSP shows an apparent efficacy in treating PCH and is worthy of
      application in clinical practice.

PMID- 19407950
TI  - Effect of serum from overfatigue rats on JNK/c-Jun/HO-1 pathway in human
      umbilical vein endothelial cells and the intervening effect of Tongxinluo
      superfine powder.
AB  - OBJECTIVE: To cultivate human umbilical vein endothelial cells (HUVECs) in the
      serum of overfatigue rats with the intervention of Tongxinluo superfine powder
      (TXLSP). By examining the variation of the activity of JNK/c-Jun/HO-1 pathway,
      the possible mechanisms of vascular endothelial dysfunction under overfatigue
      conditions and the intervening effect of TXLSP were explored. METHODS: The HUVECs
      were randomly divided into the normal control group, the model group, the
      SP600125 (a specific antagonist of JNK) group, the TXLSP group and the TXLSP +
      SP600125 group. The content of carboyhemoglobin (COHb) and the leak rate of
      lactic dehydrogenase (LDH) in different groups were measured. The mRNA and
      protein expression of JNK, c-Jun, HO-1 and the phosphorylation level of c-Jun (P
      c-Jun) were detected using Western blot and PCR methods. RESULTS: Compared with
      the normal control group, the COHb level in supernatant was increased
      significantly in the model group, and the expression of HO-1, JNK, c-Jun mRNA and
      corresponding proteins and P-c-Jun were also increased remarkably. The increases
      in these parameters were significantly decreased by SP600125. TXLSP showed
      remarkable up-regulation on the expression of JNK, c-Jun, P-c-Jun and HO-1 mRNA
      and their protein expression. Compared with the SP600125 group, the expressions
      of JNK, c-Jun, P-c-Jun and HO-1 mRNA and its protein in the TXLSP+SP600125 group
      were significantly increased at different time points (P<0.05, P<0.01).
      CONCLUSIONS: The vascular endothelial dysfunction under overfatigue conditions is
      related to the activity of the JNK/c-Jun/HO-1 pathway. One of the mechanisms of
      TXLSP in improving the vascular endothelial function is to adjust the activity of
      the JNK/c-Jun/HO-1 pathway at gene and protein levels.

PMID- 19407951
TI  - Beneficial effect of HHI-I on cerebral microcirculation, blood-brain barrier in
      rats and anti-hypoxic activity in mice.
AB  - OBJECTIVE: To investigate the effect of HHI-I (I) on the cerebral
      microcirculation, the blood-brain barrier permeability in rats and anti-hypoxic
      activity in mice. METHODS: (1) The blood microcirculation of the brain in rats
      was investigated by laser Doppler flowmetry with the probes laid on the cerebral
      pia mater or inserted into the brain parenchyma. (2) The protective action of HHI
      I against the brain microcirculation disturbance induced by intravenous injection
      of high-molecular dextran (10%, 9 mL/kg) was observed. (3) The protective effect
      of HHI-I against lethal hypoxia in mice was observed with a hypoxic chamber
      containing 5% oxygen. (4) The disruption of the blood-brain barrier (BBB)
      permeability in rats was caused by phenylephrine-induced hypertension, and the
      effect of intravenous injection of HHI-I on the BBB permeability was determined
      using Evans blue as the marker. RESULTS: HHI-I could increase the blood flow of
      the cerebral microcirculation in rats and possess some protective effects on the
      brain microcirculatory disturbance. Besides, HHI-I could decrease the brain edema
      occurring in the process of lethal hypoxia in mice. While increasing the blood
      flow of brain, HHI-I could lower the BBB permeability in rats. CONCLUSION: HHI-I
      has several beneficial effects on the cerebral microcirculation, blood-brain
      barrier in rats and anti-hypoxic activity in mice.

PMID- 19407953
TI  - Effect of Chinese herbal medicine combined with acitretin capsule in treating
      psoriasis of blood-heat syndrome type.
AB  - OBJECTIVE: To observe the clinical curative effect of Chinese herbal medicine
      combined with acitretin capsule in treating psoriasis of blood-heat syndrome (P
      BH). METHODS: Eighty patients of P-BH were randomly assigned to two groups, 39 in
      Group A and 41 in Group B. Both was treated with Chinese herbal medicines for
      clearing heat, cooling blood and removing toxic substance, and acitretin capsule
      was given to Group A additionally, with 8 weeks as one therapeutic course. The
      clinical curative effect was compared between groups, and the change of psoriasis
      activity severe index (PASI) scores before and after treatment was observed.
      RESULTS: The total effective rate in Group A was 84.2% and that in Group B 68.2%,
      also showing significance between groups (P<0.01). PASI score lowered
      significantly after treatment in both groups, showing statistical significance
      (P<0.01), but no significant difference between groups. Little adverse reaction
      was found in Group B, while in Group A, the adverse reaction was of even milder
      degree, which could be alleviated by adjusting the herbal medicine and
      symptomatic treatment administration. CONCLUSIONS: The effect of Chinese herbal
      medicine combined with acitretin capsule was superior to Chinese herbal medicine
      alone in treating P-BH, but the adverse reaction of acitretin capsule could be
      alleviated by adjusting the herbs used. However, the result is waiting to be
      verified further by larger samples.

PMID- 19407952
TI  - Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal
      interstitial fibrosis in rats with unilateral ureteral obstruction.
AB  - OBJECTIVE: To investigate the possible protective effect and mechanism of
      ginsenoside Rb1 against oxidative damage and renal interstitial fibrosis on rats
      with unilateral ureteral obstruction (UUO). METHODS: In total, 80 male rats were
      randomly divided into 4 groups, 20 in each group: the sham operated group (SOR),
      UUO group, UUO with ginsenoside Rb1 treatment group (treated with intraperitoneal
      injection of 50 mg/ kg daily) and UUO with Losartan treatment group (as the
      positive control, treated with 20 mg/kg by gastrogavage per day). The rats were
      randomly sacrificed on day 3, 7 and 14 after surgery, respectively. The
      histopathologic changes of renal interstitial tissues were observed with Masson
      staining. The mRNA of transforming growth factor beta 1 (TGF-beta 1), collagen I
      and fibronectin were reversed transcribed and quantified by Real-time PCR. Enzyme
      linked immunosorbent assay was used to quantitatively detect TGF-beta 1 and 8
      hydroxy-2'-deoxyguanosine (8-OHdG) levels. P47phox protein expression was
      assessed by immunohistochemistry and Western blot analysis. RESULTS: In the UUO
      model, the obstructed kidney showed typical features of progressive renal
      tubulointerstitial fibrosis, and the levels of TGF-beta1, collagen I and
      fibronectin increased (P<0.05). As compared with the UUO group, ginsennoside Rb1
      significantly inhibited the interstitial fibrosis including tubular injury and
      collagen deposition, and decreased the levels of TGF-beta1 (P<0.05). Ginsenoside
      Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative
      stress (P<0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox,
      a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P<0.05).
      CONCLUSION: Ginsenoside Rb1 can obviously inhibit renal interstitial fibrosis in
      rats with UUO, its mechanism possibly via against the oxidative damage and
      suppressing TGF-beta1 expression.

PMID- 19407955
TI  - Effect of composite salvia injection on platelet parameters in children with
      anaphylactoid purpura.
AB  - OBJECTIVE: To explore the effect of composite salvia injection (CSI) on platelet
      parameters in children with anaphylactoid purpura (AP) and its clinical
      significance. METHODS: One hundred and fifty children with AP were assigned to
      two groups, 80 in Group A and 70 in Group B. They were treated, respectively,
      with conventional therapy only or conventional therapy combined with CSI. Their
      platelet parameters, including blood platelet count (BPC), mean platelet volume
      (MPV), platelet distribution width (PDW) and plateletcrit (PCT) were determined
      at the acute stage and convalescent stage, respectively. RESULTS: At the acute
      stage, the BPC in AP children of both groups was in the normal range, but
      significant abnormality was shown in the levels of MPV, PDW and PCT. As for
      comparisons of these parameters at the convalescent stage, significant difference
      between the two groups was also shown in terms of MPV, PDW and PCT (P<0.05 or
      P<0.01). CONCLUSION: Although platelet shows no quantitative change in the
      pathogenic process of AP, important functional changes are surely existent. CSI
      could promote the normalization of platelet function.

PMID- 19407954
TI  - Treatment of severe aplastic anemia by immunosuppressor anti-lymphocyte
      globulin/anti-thymus globulin as the chief medicine in combination with Chinese
      drugs.
AB  - OBJECTIVE: To study the therapeutic effect of combined therapy with Chinese drugs
      and immuno-suppressors, mainly anti-lymphocyte globulin/anti-thymus globulin
      (ALG/ATG), for the treatment of severe aplastic anemia (SAA), the efficacy
      associated factors and adverse effects as well. METHODS: A retrospective analysis
      was conducted on 65 patients with SAA treated by combined therapy which was
      supplemented with cyclosporin A, androgen, hematopoietic growth factor, etc.
      RESULTS: Of the 57 patients followed-up, 26 (45.6%) were basically cured, 15
      (26.3%) remitted, and 8 (14.0%) improved markedly, the total effective rate being
      85.9%. By separately comparing with a single item of clinical data, it was shown
      that the therapeutic effectiveness was correlated, to a certain extent, with age,
      illness duration, neutrophil count, and bone marrow proliferation in patients
      before treatment, as well as with infection that occurred in the follow-up
      period. It was obviously higher in patients with peripheral neutrophil count >
      0.5 x 10 10(9)/L (P<0.05). Various degrees of serum sickness-like reactions
      occurred in the treatment of 36 patients, including fever in 36 (63.2%), skin
      rash in 8 (14.0%), and musculoskeletal pain in 5 (8.8%). CONCLUSIONS: The
      therapeutic effect of combined therapy with Chinese drugs and ALG/ATG in treating
      SAA could be affirmed, showing some superiority as compared with Western medicine
      alone. The patients' age, duration of illness, neutrophil count, and bone marrow
      proliferation before treatment, and degree of infection that occurred could
      affect the therapeutic efficacy to a certain extent. Adverse reactions resulting
      from the combined therapy are less, showing the toxicity reducing and effect
      enhancing action of Chinese drugs.

PMID- 19407956
TI  - Integrative medicine in clinical practice: from pattern differentiation in
      traditional Chinese medicine to disease treatment.

PMID- 19407957
TI  - Tanshinone IIA: a potent, natural anti-carcinogenic agent for the management of
      systemic malignancies.

PMID- 19407959
TI  - Progress of research on Inonotus obliquus.
AB  - Inonotus obliquus has high nutritional and medicinal value, especially in
      treating malignant tumors, diabetes, cardiovascular disease and AIDS, attracting
      significant attention from scholars in recent years. In this paper, the
      biological characteristics, chemical composition and pharmacologic effects of
      Inonotus obliquus were summarized. And the applications in medicine and food were
      introduced. Future research on Inonotus obliquus was also discussed in order to
      make Inonotus obliquus obtain effective exploitation and satisfy people's
      demands.

PMID- 19407961
TI  - This month in APR.

PMID- 19407962
TI  - Innovative vaccine production technologies: the evolution and value of vaccine
      production technologies.
AB  - This review paper provides an overview of innovative technologies designed to
      produce bacterial, viral, recombinant subunit, and polysaccharide vaccines, as
      well as combination vaccines. Advances in this field are illustrated by vaccines
      against DTP (diphtheria-tetanus-pertussis), influenza, hepatitis B (HepB) and
      typhoid fever. In addition, technological trends regarding antigens, adjuvants,
      and preservatives in vaccines are discussed. The progress achieved in vaccine
      production technologies is especially important for improving the protection of
      vulnerable populations against infectious diseases. These at-risk groups include
      infants, the elderly and immunocompromized individuals, as well as people living
      in developing countries or emerging economies.

PMID- 19407963
TI  - Synthesis and docking studies of new 1,4-dihydropyridines containing 4-(5)-Chloro
      2-ethyl-5-(4)-imidazolyl substituent as novel calcium channel agonist.
AB  - 1,4-Dihydropyridines have been recognized as calcium channel agonist. Three new
      analogues of Bay K8644 in which the ortho trifluromethyl phenyl group at position
      4 is replaced by the 4-(5)-Chloro-2-ethyl-5-(4)-imidazolyl substituent, were
      designed and synthesized as calcium channel agonist. For this propose, the
      structures of designed compounds were drawn by HYPERCHEM program. Conformations
      of the compounds were optimized through semi-empirical method followed by PM3
      calculation. Then the crystalin stucture of L-type calcium channel was obtained
      from the Protein Data Bank (PDB) server. Docking calculations were carried out
      using Auto-Dock.4 program. The good interaction of our 1,4-DHP derivatives showed
      that they can be as possible calcium channel agonist agents. Finally compounds
      were synthesized according to a modified Hantzsch condensation procedure.

PMID- 19407964
TI  - Anti-acne activities of pulsaquinone, hydropulsaquinone, and structurally related
      1, 4-quinone derivatives.
AB  - Quinone type compound, pulsaquinone 1, isolated from the aqueous ethanol extract
      of the roots of Pulsatilla koreana exhibited antimicrobial activities against an
      anaerobic non-spore-forming gram-positive bacillus, Propionibacterium acnes,
      which is related with the pathogenesis of the inflamed lesions in a common skin
      disease, acne vulgaris. Compound 1 was unstable on standing and thus converted to
      more stable compound 2, namely hydropulsaquinone by hydrogenation, whose activity
      was comparable to mother compound 1 (MIC for 1 and 2 against P. acnes: 2.0 and
      4.0 microg/mL, respectively). Other structurally-related quinone derivatives (3
      13) were also tested for structure-activity relationship against anaerobic and
      aerobic bacteria, and fungi. The antimicrobial activity was fairly good when the
      quinone moiety was fused with a nonpolar 6- or 7-membered ring on the right side
      whether or not conjugated (1,4-naphtoquinone derivatives 3-5), while simple
      quinone compounds 6-9 showed poor activity. It seems that the methoxy groups at
      the left side of the quinone function deliver no considerable antimicrobial
      effect.

PMID- 19407965
TI  - Farnesyl protein transferase inhibitory components of Polygonum multiflorum.
AB  - The methanolic extract of the roots of Polygonum multiflorum (Polygonaceae) was
      found to show inhibitory activity towards farnesyl protein transferase (FPTase).
      Bioassay-guided fractionation of the methanolic extract resulted in the isolation
      of two anthraquinone glycosides, as inhibitors of FPTase. These compounds
      inhibited the FPTase activity in a dose-dependent manner.

PMID- 19407966
TI  - A new furofuran lignan from Isodon japonicus.
AB  - A new sesamin type furofuran lignan, (-)-sesamin-2,2'-diol (1), along with two
      known flavonoids (2 and 3) and three phenolic compounds (4-6) were isolated from
      the aerial parts of Isodon japonicus. The structures of these compounds were
      determined by analysis of spectroscopic data (1D-, 2D-NMR, HRMS and CD) and by
      comparison of the data with those of related metabolites.

PMID- 19407967
TI  - Asian ginseng enhances the anti-proliferative effect of 5-fluorouracil on human
      colorectal cancer: comparison between white and red ginseng.
AB  - Previous studies showed that Asian ginseng, Panax ginseng C.A. Meyer, may have
      anti-cancer properties. However, there is limited data exploring the use of Asian
      ginseng as an adjuvant to chemotherapy, and minimal mechanistic studies related
      to their possible synergistic activities. In this study, the content of 8
      ginsenosides, Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1 and Rg3, in the extracts of white
      ginseng (WG) and red ginseng (RG) were determined by HPLC. Using HCT-116 human
      colorectal cancer cells, we compared the efficacy of WG and RG. We evaluated the
      synergy between ginseng and 5-fluorouracil (5-FU), and explored the mechanism of
      their anti-proliferative effects. As single extract, WG or RG used at
      concentrations of 0.1, 0.2 and 0.3 mg/mL, inhibited HCT-116 cell proliferation in
      a concentration-related manner. WG at 0.2 mg/mL did not show obvious synergy with
      5-FU co-treatment, while RG at 0.2 and 0.3 mg/mL significantly enhanced the anti
      proliferative effects of 5-FU at concentrations of 10, 50 and 100 microM (P <
      0.05). Using flow cytometric assay, RG 0.3 mg/mL did not affect cancer cell
      apoptotic induction activity. However, the RG induced cell cycle arrest in the G1
      phase, while 5-FU arrested the cell in the S phase. Different ginsenoside
      profiles are responsible for the observed differences in pharmacological effects.
      The effects of 8 ginsenosides on HCT-116 cells were assayed. Rd and Rg3 showed
      positive anti-proliferative effect. Our data suggested a potential for RG as an
      adjuvant therapy in the treatment of colorectal cancer, via a synergistic action.

PMID- 19407968
TI  - New anthracene glycosides from Rhodomyrtus tomentosa stimulate osteoblastic
      differentiation of MC3T3-E1 cells.
AB  - Two new anthracene glycosides (1, 2) were isolated from aerial parts of
      Rhodomyrtus tomentosa, along with three known compounds (3-5). The structures of
      two new compounds were established to be 4,8,9,10-tetrahydroxy-2,3,7
      trimethoxyanthracene-6-O-beta-D-glucopyranoside (1) and 2,4,7,8,9,10-hexahydroxy
      3-methoxyanthracene-6-O-alpha-L-rhamnopyranoside (2) based on spectroscopic and
      chemical methods. Among them, compound 1, 2, and 5 significantly (P<0.05)
      increased the alkaline phosphatase activity, collagen synthesis, and
      mineralization of the nodules of MC3T3-E1 osteoblastic cells compared to those of
      the control, respectively.

PMID- 19407969
TI  - Fluorenone alkaloid from Caulophyllum robustum Maxim. with anti-myocardial
      ischemia activity.
AB  - A new fluorenone alkaloid (caulophine) was isolated from the radix of
      Caulophyllum robustum Maxim. (collected from the Qinling mountains) using cell
      membrane chromatography as the screening method. Caulophine was identified as 3
      (2-(dimethylamino)ethyl)-4,5-dihydroxy-1,6-dimethoxy-9H-fluoren-9-one based on
      physicochemic and spectroscopic analyses, particularly by NMR spectroscopic data
      (i.e., COSY, HMQC, HMBC, NOESY). Caulophine possessed anti-myocardial ischemia
      activity.

PMID- 19407970
TI  - Analgesic activity of myricetin isolated from Myrica rubra Sieb. et Zucc. leaves.
AB  - Myrica rubra Sieb. et Zucc. leaves are commonly used as an astringent,
      antidiarrheic, and analgesics in folk medicine in China. In the present study,
      the analgesic activity of myricetin, a major compound in Myrica rubra Sieb. et
      Zucc. leaves was evaluated in vivo. The analgesic effect of myricetin was tested
      by a serial of models, such as acetic acid-induced writhing response, formalin
      induced paw licking and hot plate test. The sedative activity was evaluated by
      pentobarbital-induced sleep time. Platelet aggregation induced by collagen and
      arachidonic acid was also performed in vitro. Myricetin showed a significant
      inhibition on chemical nociceptive models such as the acetic acid-induced
      writhing response and the licking time on the late phase in the formalin test in
      a dose-dependent manner, but did not manifest a signicant effect in hot plate
      test. Myricetin was also not able to increase the sleeping time induced by
      pentobarbital, which further indicated that the analgesic effect of myricetin was
      unrelated to sedation. In addition, myricetin inhibited the content of PGE2 in
      the peritoneal fluid and platelet aggregation induced by collagen and arachidonic
      acid in vitro. These results collectively demonstrated that myricetin possessed
      potent analgesic activity, which was related with peripheral analgesia, but, not
      with the opioid system. Myricetin may be a potent COX-1 inhibitor with anti
      platelet activity.

PMID- 19407971
TI  - Regulation of adipocyte differentiation by histone deacetylase inhibitors.
AB  - In this study, we investigated the effects of various histone deacetylase (HDAC)
      inhibitors on adipocyte differentiation. Treatment of 3T3-L1 cells with HDAC
      inhibitors such as apicidin, trichostatin A, or suberoylanilide hydroxamic acid,
      under conditions that normally promote differentiation led to a dramatic
      attenuation of adipocyte differentiation. In contrast, sodium butyrate (NaB)
      treatment increased adipocyte differentiation. Accordingly, the expression of
      adipogenic marker genes such as FAS, aP2, PPARgamma, resistin, C/EBPalpha,
      ADD1/SREBP1c, and adiponectin were inhibited by apicidin treatment but not NaB,
      indicating that the adipocyte differentiation process could be differentially
      regulated depending on the type of HDAC inhibitor utilized. In addition, this
      differential effect seemed not to be due to disruption of the insulin- signaling
      pathway. Interestingly, our data showed that apicidin treatment could induce
      dedifferentiation of fully differentiated adipocytes, as evident by the fact that
      apicidin treatment led to a decrease of Oil Red O-stained adipocytes with a
      concomitant reduction in the expression levels of adipogenic marker genes.
      Collectively, our results suggest that adipocyte differentiation and
      dedifferentiation may be regulated by HDAC inhibitors.

PMID- 19407972
TI  - Difference in growth suppression and apoptosis induction of EGCG and EGC on human
      promyelocytic leukemia HL-60 cells.
AB  - Growth suppression and apoptosis inducing effect of (-)-epigallocatechin 3
      gallate (EGCG) and (-)-epigallocatechin (EGC) were studied against human
      promyeolcytic leukemia, HL-60 cells. EGCG showed higher growth suppression
      against HL-60 cells than EGC. IC(50) values for EGCG were 60.0 microM and EGC was
      107.7 microM, respectively. Both EGCG and EGC induced apoptosis evidenced by
      nuclei fragmentation. Nuclear fragmentation was observed as a time-dependent
      manner and the extent of nuclear fragmentation was slightly higher in EGCG
      treated cells than EGC-treated cells. The expression level of Bcl-2 was decreased
      and caspase-3 was activated by EGCG or EGC treatment. The extent in decrease of
      Bcl-2 and activation caspase-3 were more extensively occurred in EGCG-treated
      cells than in EGC-treated cells. These data corresponded to the growth
      suppression data. EGC showed no cytotoxicity to a normal V79-4 cell line and EGCG
      showed slight cytotoxicity at higher concentrations.

PMID- 19407973
TI  - Effect of tacrolimus derivatives on immunosuppression.
AB  - In this study, the effects of the FK506-mPEG on immune cell activity, skin
      grafting rejection, and Freund's complete adjuvant arthritis were investigated.
      The proliferation of T cells was inhibited with increase with the FK506 and FK506
      mPEG concentrations. FK506 and FK506-mPEG at concentrations between 0.01 nM and
      1000 nM had very similar effects on the proliferation of the T cells. On the
      other hand, in the case of the proliferation of T cells by calcium ionophore
      A23187 (1 microM), when the FK506-mPEG concentration was increased from 0.01 to
      1000 mM, the proliferation was decreased from 90.8 to 40.3%. This was 1.8-fold
      higher than that of paramethoxyamphetamine (PMA). The inhibitory effect of FK506
      mPEG on mast cell proliferation was higher than that of FK506. When B cells were
      cultured for 7 days in basal medium with no pokeweed mitogen (PWM), the IgG
      production was 156.2 ng/mL. On the other hand, in the case of the same treatment
      with 0.25% of PWM, it was 876.4 ng/mL. This is about 5.6-fold higher than with no
      PWM. These results show that FK506-mPEG may be practically applicable as a
      prodrug for the immunosuppressant FK506.

PMID- 19407974
TI  - Pharmacokinetics of verproside after intravenous and oral administration in rats.
AB  - Verproside, a catalpol derivative iridoid glucoside isolated from
      Pseudolysimachion longifolium, is a candidate for anti-asthmatic drug. The dose
      dependency of the pharmacokinetics of verproside was evaluated in rats after
      intravenous and oral administration. After intravenous administration of
      verproside (2, 5 and 10 mg/kg doses), the systemic clearance (Cl) was
      significantly reduced and AUC was significantly increased at 10 mg/kg dose
      compared to 2 and 5 mg/kg doses. The volume of distribution at steady state (V
      (ss)) remained unchanged as the dose was increased. The extent of urinary
      excretion was low for both intravenous (3.3-6.2%) and oral (0.01-0.04%) doses.
      Isovanilloylcatalpol was identified as a metabolite after intravenous
      administration of verproside and showed the significant decreases in AUC and C
      (max) at 10 mg/kg verproside dose. The reduced systemic clearance of verproside
      at high doses appears to be due to the saturable metabolism. Upon oral
      administration of verproside (20, 50 and 100 mg/kg doses), C (max) was
      nonlinearly increased. The extent of verproside recovered from the
      gastrointestinal tract at 24 h after oral administration was 0.01-0.72% for all
      three doses studied. The absolute oral bioavailability (F) was 0.3 and 0.5% for
      50 and 100 mg/kg doses, respectively. Low F appears to be due to first-pass
      metabolism.

PMID- 19407975
TI  - Gingerol inhibits cisplatin-induced vomiting by down regulating 5
      hydroxytryptamine, dopamine and substance P expression in minks.
AB  - OBJECTIVE: To investigate the antiemetic effect of gingerol and its multi-targets
      effective mechanism on 5-hydroxytryptamine (5-HT), dopamine (DA) and substance P
      (SP). The antiemetic effect of gingerol was investigated on a vomiting model of
      mink induced by cisplatin (7.5 mg . kg(-1), i.p.) in 6 h observation. The levels
      of 5-HT, DA and distribution of substance P in the area postrema and ileum were
      measured by high performance liquid chromatography (HPLC) and
      immunohistochemistry respectively. The frequency of cisplatin induced retching
      and vomiting was significantly reduced by pretreatment with gingerol in a dose
      dependent manner (P<0.05). Cisplatin produced a significant increase in 5-HT and
      DA levels in the area postrema and ileum of minks (P<0.05), and this increase was
      significantly inhibited by gingerol in a dose-dependent manner (P<0.05).
      Substance P-immunoreactive was mainly situated in the mucosa and submucosa of
      ileum as well as in the neurons of area postrema, and gingerol markedly
      suppressed the increase immunoreactivity of substance P induced by cisplatin in a
      dose-dependent manner (P<0.05). Gingerol has good activity against cisplatin
      induced emesis in minks possibly by inhibiting central or peripheral increase of
      5-HT, DA and substance P.

PMID- 19407976
TI  - Tetrazolium violet induces apoptosis via caspases-8, -9 activation and Fas/FasL
      up-regulation in rat C6 glioma cells.
AB  - Tetrazolium violet (TV), a tetrazolium salt, was synthesized as a novel and
      potent anticancer agent with a broad spectrum of anticancer activity against many
      cancer cells. A previous study showed that tetrazolium violet inhibited cell
      growth, and induced cell cycle arrest and apoptosis in C6 Rat glioma cells. It
      also showed that treatment of cells with TV for 24 h resulted in a dramatic up
      regulation of p53, and an increase in the activity of caspase-3, accompanied with
      a significant increase of Bax/Bcl-2 ratio. In this study, we further investigated
      which Fas/FasL and caspase were activated by TV during the apoptosis. Annexin-V
      propidium iodide (PI) binding assay and nucleosome ELISA assay further indicated
      that TV induced a typical apoptosis, in a time-dose-dependent manner. The data
      showed that the activity of Fas/FasL and caspase-8 and -9 were significantly
      enhanced by the compound, which suggested that TV might be used as a Fas/FasL and
      caspases promoter to initiate brain cancer cell apoptosis.

PMID- 19407977
TI  - Resveratrol inhibits Porphyromonas gingivalis lipopolysaccharide-induced
      endothelial adhesion molecule expression by suppressing NF-kappaB activation.
AB  - P. gingivalis is a major pathogen that is involved in the onset and progression
      of periodontal disease. This study investigated the effect of resveratrol, a
      naturally occurring polyphenol, on P. gingivalis LPS-accelerated vascular
      inflammation, a key step in the progression of periodontitis. Resveratrol
      significantly inhibited the P. gingivalis LPS-induced adhesion of leukocytes to
      endothelial cells and to the aortic endothelium by down-regulating the cell
      adhesion molecules, ICAM-1 and VCAM-1. Moreover, the inhibition of the P.
      gingivalis LPS-induced cell adhesion molecules by resveratrol was mainly mediated
      by nuclear factor-kappaB (NF-kappaB). Resveratrol suppressed P. gingivalis LPS
      stimulated IkappaBalpha phosphorylation and nuclear translocation of the p65
      subunit of NF-kappaB in HMECs. Overall, these findings suggest that resveratrol
      significantly attenuates the P. gingivalis LPS-induced monocyte adhesion to the
      endothelium by suppressing the expression of the NF-kappaB-dependent cell
      adhesion molecules, suggesting its therapeutic role in periodontal pathogen
      induced vascular inflammation.

PMID- 19407978
TI  - Inhibitory effects of clotrimazole on TNF-alpha-induced adhesion molecule
      expression and angiogenesis.
AB  - Cell adhesion molecules play a pivotal role in chronic inflammation and
      pathological angiogenesis. In the present study, we investigated the inhibitory
      effects of clotrimazole (CLT) on tumor necrosis factor (TNF)-alpha-induced
      changes in adhesion molecule expression. CLT dose-dependently inhibited monocyte
      chemoattractant protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM
      1), and vascular cell adhesion molecule-1 (VCAM-1) expressions in TNF-alpha
      stimulated HT29 colonic epithelial cells. This inhibitory action of CLT
      correlated with a significant reduction in TNF-alpha-induced adhesion of
      monocytes to HT29 cells, which was comparable to the inhibitory effects of anti
      ICAM-1 and VCAM-1 monoclonal antibodies on monocyte-epithelial adhesion. These
      inhibitory actions of CLT were, at least in part, attributable to the inhibition
      of redox sensitive NF-kappaB activation, as CLT inhibited TNF-alpha-induced ROS
      generation as well as NF-kappaB nuclear translocation and activation in HT29
      cells. Furthermore, the inhibition of TNF-alpha-induced monocyte adhesion was
      also mimicked by the specific NF-kappaB inhibitor, pyrrolidine dithiocarbamate
      (PDTC). Inflammatory mediators including TNF-alpha have known to promote
      angiogenesis, which in turn further contributes to inflammatory pathology.
      Therefore, we additionally evaluated whether CLT modulates TNF-alpha-induced
      angiogenesis using in vivo chick chorioallantoic membrane (CAM) assay. The CAM
      assay showed that CLT dose-dependently attenuated TNF-alpha-induced angiogenesis,
      and the effect was correlated with decreased inflammation of the CAM tissue. In
      conclusion, our results suggest that CLT can inhibit TNF-alpha-triggered
      expression of adhesion molecules, ICAM-1 and VCAM-1, and angiogenesis during
      inflammation.

PMID- 19407979
TI  - A simple HPLC method for doxorubicin in plasma and tissues of nude mice.
AB  - Doxorubicin is a cytotoxic anthracycline that has been used for the treatment of
      several malignancies. Several HPLC methods have been reported for the
      quantification of doxorubicin in biological samples. Tissue matrix effect and
      sample size requirements, however, have been remaining issues for simple and easy
      to-adapt analytical methods in small animal experiments. The present study
      established a simple HPLC method for doxorubicin in plasma and tissues (tumor,
      heart, spleen, liver, gastrointestinal tract, brain, lung, and kidney) of nude
      mice. Our method required a small sample volume (100 microL plasma and 10 mg
      tissue), which made it possible to use each blank tissue for calibration curves.
      The limit of quantification was 25 ng/mL in plasma and 0.1 to 0.4 microg/mg in
      other tissues with recovery rates ranging from 52.4 to 95.2%. The linearity,
      accuracy and precision in all tissues, except gastrointestinal tract (GIT), were
      found to be acceptable in the range of 25-2000 ng/mL plasma and 0.1-4 ng/mg
      tissue. This method was used successfully to determine the drug concentration in
      plasma and tissues of human tumor xenograft-bearing nude mice given intratumoral
      doxorubicin in a polymeric drug delivery system designed for sustained release.
      In conclusion, the present method may be useful as a simple and easy-to-adapt,
      yet, sensitive analytical method of doxorubicin for plasma and tissue
      pharmacokinetic studies in small animals such as nude mice.

PMID- 19407981
TI  - Oltipraz promotion of liver regeneration after partial hepatectomy: The role of
      PI3-kinase-dependent C/EBPbeta and cyclin E regulation.
AB  - Oltipraz, a representative cancer chemopreventive agent, regenerates cirrhotic
      liver via CCAAT/enhancer binding protein beta (C/EBPbeta). This study examined
      the effect of oltipraz on liver regeneration after partial hepatectomy (PH) and
      explored the role of phosphatidylinositol 3-kinase (PI3K) pathway responsible in
      liver regeneration. Oltipraz treatment (30 mg/kg/day, for 3 days) promoted liver
      regeneration in PH rats, but did not increase hepatocyte growth factor
      production. Subcellular fractionation and electrophoretic mobility shift assays
      showed that oltipraz treatment increased C/EBPbeta-DNA binding activity in the
      liver of sham control rats and further enhanced PH-mediated nuclear translocation
      of C/EBPbeta. The expression of cyclin E and the activity of cyclin E-dependent
      kinase were both enhanced by oltipraz treatment of PH rats. The signaling pathway
      that controls C/EBPbeta and cyclin E were studied in H4IIE cells, a rat-derived
      hepatocyte cell line. Oltipraz potentiated the nuclear accumulation of C/ EBPbeta
      and C/EBPbeta-DNA binding activity in cells incubated in a medium containing
      serum. PI3K and its downstream kinase, p70S6 kinase, were both required for
      C/EBPbeta-dependent induction of cyclin E by oltipraz, as shown by chemical
      inhibition and plasmid transfection experiments. The results of this study
      demonstrate that oltipraz treatment enhances liver regeneration after PH, which
      involves activation of C/EBPbeta and C/EBPbeta-dependent cyclin E expression via
      the PI3K-p70S6 kinase pathway.

PMID- 19407980
TI  - Anti-inflammatory effect of Trichostatin-A on murine bone marrow-derived
      macrophages.
AB  - Histone deacetylase (HDAC) inhibitors were recently shown to suppress
      inflammatory responses in models of autoimmune and inflammatory diseases. In this
      study, the anti-inflammatory effects of five different HDAC inhibitors on
      lipopolysaccharide-(LPS)-stimulated macrophages were compared and the mechanisms
      of these effects were demonstrated. Trichostatin-A (TSA) and scriptaid, two of
      the five HDAC inhibitors, showed the most potent inhibitory effects on the nitric
      oxide (NO) production of RAW264.7 cells and bone-marrow-derived macrophages
      (BMDMs). TSA significantly decreased the mRNA and protein levels of the
      proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-6, and IL-1beta, whereas the pretreatment with TSA increased the level of
      the immunosuppressive cytokine IL-10. TSA also reduced the cell surface markers
      of the maturity of the macrophages. Furthermore, a longer duration (up to 8 h) of
      hyperacetylation was observed in the cells that had been exposed to TSA, whereas
      the hyperacetylation induced by the other HDAC inhibitors was absent after 8 h.
      These results demonstrated that TSA is the most potent HDAC inhibitor of histone
      deacetylation and has the greatest ability to induce anti-inflammatory activity
      in cloned and naive macrophages. These results are expected to serve as a guide
      for future studies on the ability of HDAC inhibitors to inhibit acute and chronic
      inflammatory diseases.

PMID- 19407982
TI  - Quantitative trait loci conferring grain mineral nutrient concentrations in durum
      wheat x wild emmer wheat RIL population.
AB  - Mineral nutrient malnutrition, and particularly deficiency in zinc and iron,
      afflicts over 3 billion people worldwide. Wild emmer wheat, Triticum turgidum
      ssp. dicoccoides, genepool harbors a rich allelic repertoire for mineral
      nutrients in the grain. The genetic and physiological basis of grain protein,
      micronutrients (zinc, iron, copper and manganese) and macronutrients (calcium,
      magnesium, potassium, phosphorus and sulfur) concentration was studied in
      tetraploid wheat population of 152 recombinant inbred lines (RILs), derived from
      a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16). Wide
      genetic variation was found among the RILs for all grain minerals, with
      considerable transgressive effect. A total of 82 QTLs were mapped for 10 minerals
      with LOD score range of 3.2-16.7. Most QTLs were in favor of the wild allele (50
      QTLs). Fourteen pairs of QTLs for the same trait were mapped to seemingly
      homoeologous positions, reflecting synteny between the A and B genomes.
      Significant positive correlation was found between grain protein concentration
      (GPC), Zn, Fe and Cu, which was supported by significant overlap between the
      respective QTLs, suggesting common physiological and/or genetic factors
      controlling the concentrations of these mineral nutrients. Few genomic regions
      (chromosomes 2A, 5A, 6B and 7A) were found to harbor clusters of QTLs for GPC and
      other nutrients. These identified QTLs may facilitate the use of wild alleles for
      improving grain nutritional quality of elite wheat cultivars, especially in terms
      of protein, Zn and Fe.

PMID- 19407983
TI  - Multiple alleles at Early flowering 1 locus making variation in the basic
      vegetative growth period in rice (Oryza sativa L.).
AB  - A recently established rice breeding program in low latitudes aims to develop
      varieties with extremely long basic vegetative growth (BVG) periods and weak
      photoperiod sensitivities. The Taiwanese japonica variety Taichung 65 (T65)
      harbors a recessive allele ef1 at the Ef1 (Early flowering 1) locus, thereby
      exhibiting an extremely long BVG period. The previous reported functional allele
      Ehd1 (Early heading date 1), located on chromosome 10, encodes a B-type response
      regulator, thereby shortening the BVG period, whereas its nonfunctional allele
      ehd1 greatly prolongs the BVG period. A conventional analysis using F(2) and F(3)
      populations and a subsequent CAPS analysis based on the amino acid sequences of
      Ehd1 and ehd1 showed that Ef1 and Ehd1 were at the same locus. The CAPS analysis
      also indicated that the Taiwanese japonica varieties with extremely long BVG
      periods all harbor ef1, but that ef1 does not exist among indica and japonica
      varieties in the low latitudes. Since ef1 has not been found in any japonica
      varieties outside Taiwan, this allele might have originated in Taiwan. Sequence
      analysis revealed that the mutant allele ef1-h, which prolongs the BVG period
      even more than ef1 does, harbors an mPing insertion in exon 2, which causes the
      complete loss of gene function. Our results indicate that both ef1 or ef1-h
      alleles can be used as new gene sources in developing rice varieties with
      extremely long BVG periods for low latitudes.

PMID- 19407984
TI  - Scarlet-Rz1, an EMS-generated hexaploid wheat with tolerance to the soilborne
      necrotrophic pathogens Rhizoctonia solani AG-8 and R. oryzae.
AB  - The necrotrophic root pathogens Rhizoctonia solani AG-8 and R. oryzae cause
      Rhizoctonia root rot and damping-off, yield-limiting diseases that pose barriers
      to the adoption of conservation tillage in wheat production systems. Existing
      control practices are only partially effective, and natural genetic resistance to
      Rhizoctonia has not been identified in wheat or its close relatives. We report
      the first genetic resistance/tolerance to R. solani AG-8 and R. oryzae in wheat
      (Triticum aestivum L. em Thell) germplasm 'Scarlet-Rz1'. Scarlet-Rz1 was derived
      from the allohexaploid spring wheat cultivar Scarlet using EMS mutagenesis.
      Tolerant seedlings displayed substantial root and shoot growth after 14 days in
      the presence of 100-400 propagules per gram soil of R. solani AG-8 and R. oryzae
      in greenhouse assays. BC(2)F(4) individuals of Scarlet-Rz1 showed a high and
      consistent degree of tolerance. Seedling tolerance was transmissible and appeared
      to be dominant or co-dominant. Scarlet-Rz1 is a promising genetic resource for
      developing Rhizoctonia-tolerant wheat cultivars because the tolerance trait
      immediately can be deployed into wheat breeding germplasm through cross
      hybridization, thereby avoiding difficulties with transfer from secondary or
      tertiary relatives as well as constraints associated with genetically modified
      plants. Our findings also demonstrate the utility of chemical mutagenesis for
      generating tolerance to necrotrophic pathogens in allohexaploid wheat.

PMID- 19407985
TI  - Identification and genetic mapping of pm42, a new recessive wheat powdery mildew
      resistance gene derived from wild emmer (Triticum turgidum var. dicoccoides).
AB  - Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most
      important wheat diseases worldwide in areas with cool or maritime climates. Wild
      emmer (Triticum turgidum var. dicoccoides) is an important potential donor of
      disease resistances and other traits for common wheat improvement. A powdery
      mildew resistance gene was transferred from wild emmer accession G-303-1M to
      susceptible common wheat by crossing and backcrossing, resulting in inbred line
      P63 (Yanda1817/G-303-1 M//3*Jing411, BC(2)F(6)). Genetic analysis of an F(2)
      population and the F(2:3) families developed from a cross of P63 and a
      susceptible common wheat line Xuezao showed that the powdery mildew resistance in
      P63 was controlled by a single recessive gene. Molecular markers and bulked
      segregant analysis were used to characterize and map the powdery mildew
      resistance gene. Nine genomic SSR markers (Xbarc7, Xbarc55, Xgwm148, Xgwm257,
      Xwmc35, Xwmc154, Xwmc257, Xwmc382, Xwmc477), five AFLP-derived SCAR markers
      (XcauG3, XcauG6, XcauG10, XcauG20, XcauG22), three EST-STS markers (BQ160080,
      BQ160588, BF146221) and one RFLP-derived STS marker (Xcau516) were linked to the
      resistance gene, designated pm42, in P63. pm42 was physically mapped on
      chromosome 2BS bin 0.75-0.84 using Chinese Spring nullisomic-tetrasomic,
      ditelosomic and deletion lines, and was estimated to be more than 30 cM proximal
      to Xcau516, a RFLP-derived STS marker that co-segregated with the wild emmer
      derived Pm26 which should be physically located in 2BS distal bin 0.84-1.00. pm42
      was highly effective against 18 of 21 differential Chinese isolates of B.
      graminis f. sp. tritici. The closely linked molecular markers will enable the
      rapid transfer of pm42 to wheat breeding populations thus adding to their genetic
      diversity.

PMID- 19407986
TI  - Identification and characterization of the erect-pose panicle gene EP conferring
      high grain yield in rice (Oryza sativa L.).
AB  - The breeding of japonica varieties with erect-pose panicle (EP) has recently
      progressed in the northern part of China, because these varieties exhibit a far
      higher grain yield than the varieties with normal-pose panicle (NP). A genetic
      analysis using the F(2) population from the cross between Liaojing5, the first
      japonica EP variety in China, and the Japanese japonica NP variety Toyonishiki
      revealed that EP is governed by a single dominant gene EP. Based on previous
      studies, map-based cloning of EP locus was conducted using Liaojing5,
      Toyonishiki, their F(2) population, and a pair of near-isogenic lines for EP
      locus (ZF14 and WF14) derived from the cross between the two varieties;
      consequently, the STS marker H90 was found to completely cosegregate with panicle
      pose. The H90 is located in the coding sequence AK101247 in the database, and the
      AK101247 of Liaojing5 has a 12 bp sequence in exon 5 replaced with a 637 bp
      sequence of its wild type allele. It was therefore considered that the AK101247
      encodes the protein of the wild type allele at EP locus, and that the sequence
      substitution in exon 5 of Liaojing5 is crucial for expression of the EP
      phenotype. The effects of EP gene on agronomic traits were investigated using two
      pairs of near-isogenic lines (ZF6 vs. WF6 and ZF14 vs. WF14) derived from the
      cross between the two varieties. Experimental results showed that EP gene
      markedly enhanced grain yield, chiefly by increasing number of secondary branches
      and number of grains on the secondary branch. EP gene also produced a remarkable
      increase in grain density.

PMID- 19407987
TI  - Efficiency gain of marker-assisted backcrossing by sequentially increasing marker
      densities over generations.
AB  - Expenses for marker assays are the major costs in marker-assisted backcrossing
      programs for the transfer of target genes from a donor into the genetic
      background of a recipient genotype. Our objectives were to (1) investigate the
      effect of employing sequentially increasing marker densities over backcross
      generations on the recurrent parent genome (RPG) recovery and the number of
      marker data points (MDP) required, and (2) determine optimum designs for
      attaining RPG thresholds of 93-98% with a minimum number of MDP. We simulated the
      introgression of one dominant target gene for genome models of sugar beet (Beta
      vulgaris L.) and maize (Zea mays L.) with varying marker distances of 5-80 cM and
      population sizes of 30-250 plants across BC(1) to BC(3) generations. Employing
      less dense maps in early backcross generations resulted in savings of over 50% in
      the number of required MDP compared with using a constant set of markers and was
      accompanied only by small reductions in the attained RPG values. The optimum
      designs were characterized by increasing marker densities and increasing
      population sizes in advanced generations for both genome models. We conclude that
      increasing simultaneously the marker density and the population size from early
      to advanced backcross generations results in gene introgression with a minimum
      number of required MDP.

PMID- 19407988
TI  - [Surgical dislocation of the hip for the treatment of femoroacetabular
      impingement. Technique and results].
AB  - Surgical dislocation of the hip is a safe and established technique for treating
      femoroacetabular impingement. The complication rate is low, and if the correct
      technique that respects the blood supply is used, femoral head necrosis does not
      occur. The most frequent complications are minor ectopic bone formation and
      nonunion of the greater trochanter. Surgical treatment includes the correction of
      femoral and acetabular pathology. Clinically, in approximately 75-80% of cases a
      good-to-excellent result can be obtained. However, patients with advanced
      degenerative changes (exceeding stage 1 osteoarthritis using the Tonnis score)
      have worse outcomes. It has also been shown that preservation of the labrum has a
      significant influence on both clinical outcome and progression of osteoarthritis:
      It seems that preservation of the labrum is mandatory.

PMID- 19407989
TI  - [Femoroacetabular impingement. Clinical and radiological diagnostics].
AB  - A systematic approach to the examination of the hip region is mandatory to
      identify patients with femoroacetabular impingement. The patients' age, history,
      and physical examination may lead to the correct diagnosis. Plain radiographs are
      the imaging modality of first choice. In addition to obvious findings, more
      subtle changes such as loss of offset at the head-neck transition or acetabular
      retroversion have to be assessed. For correct analysis, a high quality of the
      images must be ensured. Therefore, knowledge of the technique used to take the
      pictures seems essential. With three-dimensional reconstructed computed
      tomography, asphericities of the head-neck junction or retroversion of the
      acetabulum may be visualized. In addition to the accurate demonstration of the
      head-neck junction, magnetic resonance imaging is particularly suitable to reveal
      pathological conditions of soft tissues such as articular cartilage or labral
      lesions.

PMID- 19407991
TI  - [Femoroacetabular impingement (FAI)].

PMID- 19407990
TI  - [FAI - concept and etiology].
AB  - Femoroacetabular impingement (FAI), a recently proposed mechanical concept
      regarding the development of osteoarthritis (OA) of the hip, is gaining increased
      acceptance. Both osseous deformity and use of the hip may result in hip damage.
      Osseous deformities are seen on the acetabular (pincer) or the femoral (cam) side
      of the hip, leading to characteristic alterations of the acetabular rim. Cam FAI
      is found in 20-30-year-old athletic men, revealing deep cartilage avulsions from
      the acetabular rim while the labrum is frequently intact. In pincer FAI, found in
      30-40-year-old women, the labrum is frequently significantly destroyed with only
      minor damage to the acetabular rim. Professional or athletic impact activities
      can trigger even mild FAI deformities to become symptomatic. For some FAI
      deformities, the etiologies are known, but for most of them the exact causes are
      unknown. An improved understanding of the etiology of FAI and its role in the
      development of hip OA might lead to a reduction in the prevalence of so-called
      primary OA of the hip.

PMID- 19407993
TI  - Optical fibre SERS sensors.
AB  - Surface-enhanced Raman scattering (SERS) has established itself as an important
      analytical technique. However, efforts to transfer the technology from the
      laboratory to the production line, clinic or field have been frustrated by the
      lack of robust affordable substrates and the complexity of interfacing between
      sample and spectrometer. Prompted by the success of optical fibre systems for
      implementing normal Raman scattering spectroscopy in remote locations and
      biomedical applications, attention has now shifted to the development of SERS
      active optical fibres. Other workers have attempted to develop SERS probes with
      extended interaction lengths and both far-field and near-field SERS imaging
      techniques for high-resolution chemical mapping of surfaces. This review
      discusses the development of these technologies and presents the current state of
      the art. Although recent developments show great promise, some outstanding
      challenges and opportunities remain to be addressed.

PMID- 19407992
TI  - Cannabinoid-induced conditioned place preference in the spontaneously
      hypertensive rat-an animal model of attention deficit hyperactivity disorder.
AB  - RATIONALE: Cannabis preparations are the most widely consumed illicit drugs, and
      their use typically begins in adolescence. The prevalence of cannabis abuse is
      higher in patients with attention deficit/hyperactivity disorder (ADHD) than in
      the general population, yet, knowledge about the motivational properties of
      cannabinoids in animal models of ADHD are lacking. OBJECTIVE: To compare the
      motivational effects of the synthetic cannabinoid agonist WIN55,212-2 (WIN) in
      adolescent and adult spontaneously hypertensive rats (SHR), a validated animal
      model of ADHD, and Wistar rats, representing a "normal" genetically heterogeneous
      population. We also asked whether the effects of WIN depended (1) on the
      activation of the cerebral subtype of cannabinoid receptors, namely, the CB(1)
      cannabinoid receptor and (2) on putative changes by WIN in blood pressure.
      METHODS: WIN was tested under an unbiased conditioned place preference (CPP)
      paradigm. Blood pressure after WIN administration was also monitored in
      additional groups of rats. RESULTS: In the Wistar rats, WIN produced place
      aversion only in the adult but not adolescent rats. In contrast, WIN produced CPP
      in both adolescent and adult SHR rats. The behavioral effects of WIN were CB(1)
      mediated and not related to blood pressure. CONCLUSION: The contrasting effects
      of WIN in Wistar and SHR, and the higher resistance of adolescent rats to the
      aversive and rewarding effects of WIN in these two strains suggests that both
      adolescence and the ADHD-like profile exhibited by the SHR strain constitute
      factors that influence the motivational properties of cannabinoids.

PMID- 19407994
TI  - Action preparation enhances the processing of tactile targets.
AB  - We present two experiments in which we investigated whether tactile attention is
      modulated by action preparation. In Experiment 1, participants prepared a saccade
      toward either the left or right index finger, depending on the pitch of a non
      predictive auditory cue. In Experiment 2, participants prepared to lift the left
      or right index finger in response to the auditory cue. In half of the trials in
      both experiments, a suprathreshold vibratory stimulus was presented with equal
      probability to either finger, to which the participants made a speeded foot
      response. The results showed facilitation in the processing of targets delivered
      at the goal location of the prepared movement (Experiment 1), as well as at the
      effector of the prepared movement (Experiment 2). These results are discussed
      within the framework of theories on motor preparation and spatial attention.

PMID- 19407995
TI  - Molecular characterization of native isolates of lactic acid bacteria,
      bifidobacteria and yeasts for beneficial attributes.
AB  - In a changing scenario of food habits being associated with wellness factors
      through the concepts of probiotics and prebiotics, an attempt has been made to
      characterize on molecular basis, the desirable benefits associated with natural
      isolates of lactic acid bacteria, bifidobacteria, and yeasts. From a diverse
      range of foods and related samples, based on conventional microbiological
      protocols, three well-characterized natural isolates of Lactobacillus plantarum
      MTCC 5422, Bifidobacterium adolescentis MTCC 5423 and Saccharomyces cerevisiae
      MTCC 5421 were selected. The cultures of L. plantarum and B. adolescentis showed
      positive polymerase chain reaction (PCR) amplification with oligonucleotide
      primers targeting genus-specific 16 S rRNA for Lactobacillus and fructose-6
      phosphate phosphoketolase for Bifidobacterium. Similarly, species-specific
      positive amplification in PCR was observed with primers of phytase (acid
      phosphatase) in S. cerevisiae and alpha-D: -galactosidase and bile salt hydrolase
      in L. plantarum and B. adolescentis. The cultures of L. plantarum and B.
      adolescentis exhibited a broad spectrum antibacterial activity against selected
      foodborne pathogenic bacterial species and tolerance to acid and bile. Gene
      sequence of respective PCR-amplified products confirmed the genetic identity of
      the isolated cultures as L. plantarum and B. adolescentis showing 99% homology
      with the documented sequence of established gene bank.

PMID- 19407996
TI  - Focal lesions of the patella.
AB  - Focal lesions of the patella may be identified during the investigation of
      anterior knee pain or as an incidental finding on radiological images. This
      pictorial review describes the radiographic appearances of a wide range of
      conditions that have been seen in this sesamoid bone. Where appropriate, computed
      tomography and magnetic resonance features have been included.

PMID- 19407997
TI  - Musculoskeletal sonography of the normal foot.
AB  - Traumatic, degenerative and rheumatological injuries of the foot are common and
      can be managed by an ever increasing number of treatments and surgical
      interventions. High-frequency sonography is inexpensive, portable and is unique
      in allowing true dynamic assessment of the ligamentous, muscular and tendinous
      structures. The ultrasound technique demonstrates a steep learning curve and
      requires detailed knowledge of the foot anatomy. Ultrasound assessment plays an
      important role in the diagnosis and management of injuries of these structures by
      guiding rehabilitation and surgical intervention without delay. However, intimate
      knowledge of the ultrasound appearances of the foot anatomy and normal variants
      is paramount to correctly identify pathological conditions. We describe the
      normal sonographic appearances of the foot musculoskeletal structures with MR
      correlation including joints and their ligaments, dorsal and plantar surfaces of
      the foot, and the arches of the foot and their supporting structures.

PMID- 19407998
TI  - Clinical applications of PET amyloid imaging: an update.

PMID- 19407999
TI  - Unexpected foci of 18F-FDG uptake in the breast detected by PET/CT: incidence and
      clinical significance.
AB  - PURPOSE: The aim of this study was to evaluate the frequency and clinical
      significance of unexpected focal (18)F-fluorodeoxyglucose (FDG) uptake localized
      by PET/CT within the breast. METHODS: The files of 4,038 consecutive female
      cancer patients referred for FDG PET/CT over a period of 74 months were
      retrospectively reviewed. Patients with breast cancer were excluded from the
      study. The incidence of focal sites of increased FDG uptake localized by PET/CT
      to the breast was determined. The intensity of uptake was measured using the lean
      body mass maximum standard uptake value (LBM SUV(max)), and the presence and
      patterns of morphologic changes on CT were assessed. The etiology and clinical
      significance of findings were confirmed histologically or with imaging and
      clinical follow-up. RESULTS: Unexpected FDG foci in the breast were identified in
      33 of 4,038 patients (0.82%). Follow-up data were available for 30 patients.
      Malignancy was diagnosed in 17 patients (histology 12, clinical 5) and excluded
      in 13 patients (histology 9, clinical 4). There was a borderline statistically
      significant difference in FDG uptake (LBM SUV(max)) between malignant (3.13 +/-
      2.25) and benign (1.85 +/- 1.18) lesions (p = 0.05). Focal lesions were seen on
      CT in 23 patients (malignant 11, benign 12), and CT was negative in 7 patients
      (malignant 6, benign 1). CONCLUSION: Although rare, incidental focal abnormal FDG
      uptake in the breast may represent malignant lesions in up to 57% of patients.
      Breast incidentalomas on PET/CT warrant further assessment including tissue
      sampling to define the etiology of these unexpected FDG-avid foci.

PMID- 19408000
TI  - Myocardial perfusion quantitation with 15O-labelled water PET: high
      reproducibility of the new cardiac analysis software (Carimas).
AB  - PURPOSE: Carimas (Cardiac Image Analysis System) is a new software package
      developed at the Turku PET Centre for the quantitation of PET studies of the
      heart with a broad range of tracers. The goal of this study was to assess the
      reproducibility of results the package provides for myocardial perfusion (MP)
      quantitation using (15)O-labelled water. METHODS: Four observers with various
      levels of experience in nuclear medicine independently analysed 20 MP studies (10
      rest flow: "rest", 10 adenosine-induced hyperaemia: "stress"). Each study was
      analysed twice. The linear mixed model for repeated measures was fitted to the
      data to calculate intraclass correlation coefficients (ICC), differences between
      the repeats (the intraobserver differences) and differences between the observers
      (the interobserver differences). Also, Pearson correlation coefficients (r) were
      calculated and Bland-Altman plots were drawn. The reproducibility of MP was
      assessed on global, regional and segmental levels. Thereafter, this analysis was
      applied in 48 consecutive clinical patients with suspected coronary heart disease
      (CHD). RESULTS: For the experienced observer the Pearson r for all segments was
      0.974 at rest and 0.978 at stress (p < 0.0001), and the repeatability
      coefficients were 0.145 ml/g per min (15.5% of the average) and 0.389 ml/g per
      min (14.9%), correspondingly. The ICC reflected very good overall
      reproducibility. The intraobserver and interobserver differences were small, and
      the difference between the most and the least experienced observers at stress was
      8.5% for the global MP. The clinical accuracy of the perfusion in the detection
      of CHD was excellent (positive predictive value 91% and negative predictive value
      88%) against invasive angiography. CONCLUSION: The results demonstrate high
      reproducibility of myocardial perfusion quantitation with (15)O-labelled water
      PET using Carimas. The results support the feasibility of robust analysis and
      good clinical accuracy.

PMID- 19408001
TI  - Subtraction CT angiography for evaluation of intracranial aneurysms: comparison
      with conventional CT angiography.
AB  - The purpose of our study was to compare the diagnostic performance of subtraction
      computed tomography angiography (CTA) with conventional nonsubtracted CTA and
      digital subtraction angiography (DSA) for the detection of intracranial
      aneurysms. A total of 76 patients underwent both subtraction CTA and conventional
      CTA for the detection and therapy planning of suspected intracranial aneurysms.
      Subtraction and conventional CTA images were independently assessed by two
      readers in a blinded manner. The possibility of endovascular treatment or
      surgical clipping was also assessed based on information provided by CT
      angiograms alone. In 64 patients, 75 aneurysms were present on DSA. On a per
      aneurysm basis, the sensitivity of subtraction CTA was 98.6% for reader 1, and
      100% for reader 2. However, sensitivity of conventional CTA was 94.6% for reader
      1, and 93.3% for reader 2. Therapeutic decisions could be made regarding 63
      patients based on information provided by subtraction CTA images. However,
      conventional CTA provided sufficient information to make this decision for 55
      patients. Conventional CTA has limited sensitivity in detecting very small
      aneurysms as well as aneurysms adjacent to bone. Subtraction CTA performed on a
      64-row multidetector CT is an accurate and promising diagnostic tool that seems
      to be equivalent to 2D DSA for the detection and pretreatment planning of
      intracranial aneurysms.

PMID- 19408003
TI  - [Intravitreal injections of medications in Germany. Contract situation and legal
      conditions].
AB  - Despite the increasing application of both approved and off-label drugs for
      intravitreal administration, the German health system still does not provide an
      accounting code for the procedure of intravitreal injections. Health insurances
      and politicians are exerting pressure in order to limit the expected increase in
      the number of medications and costs due to demographic factors. Although the
      price for the drug can be determined by the manufacturer, a standing committee
      has to agree on the fee to be charged for the medical service of injection and
      subsequent examinations. Until the missing arrangement has been made, each
      individual surgeon can balance accounts with the patients who have claim for
      reimbursement. Many contracts have recently been made in order to regulate the
      extent of performance and charges for the application of medications and follow
      up examinations to reduce administration costs. Due to medical liability and
      ethical code, physicians are obliged to provide a cost-effective and adequate
      treatment as well as a comprehensive preoperative patient education including
      efficacy, potential complications, limited prescription and free choice of a
      medical practitioner. It also appears prudent to explain relevant terms such as
      'off-label' and 'level of evidence'. To prevent any suspicion of personal
      advantage, patients should be informed if placed contracts do not allow equal
      reimbursement for the same treatment or similar drugs.

PMID- 19408002
TI  - Conventional radiography and computed tomography of cardiac assist devices.
AB  - Patients intended for circulatory support by cardiac assist devices (CAD) usually
      suffer from end-stage acute or chronic heart failure. Since the introduction of
      CAD in 1963 by DeBakey and coworkers, the systems have gone through a substantial
      evolution and have been increasingly used in the intervening decades. The
      spectrum of CAD includes a variety of systems serving to assist the systolic
      function of the left ventricle, the right ventricle, or both. Conventional
      radiography and multislice spiral computed tomography (CT) are the most commonly
      used radiological techniques for imaging patients with a CAD. CT is very useful
      for evaluating CAD systems by using both two- and three-dimensional
      reconstructions of the volumetric data sets. The two techniques together allow
      for the comprehensive assessment of patients with devices by imaging the in- and
      outflow cannulae, the anastomoses, the position of the pump, as well as
      associated complications. A close collaboration with cardiac surgeons with
      expertise in the field of circulatory support is deemed necessary for adequate
      image interpretation. This article describes the technical diversity of the
      currently available CAD systems. The imaging characteristics on conventional
      radiography and multislice spiral CT as well as the typical complications of
      their use are demonstrated.

PMID- 19408004
TI  - Adenocarcinoma of the small intestine complicating Crohn's disease.

PMID- 19408005
TI  - "Necklace" fibers as a late clue to the interpretation of the forgotten
      "trilaminar" fibers.

PMID- 19408007
TI  - Comparison of energy expenditure, economy, and pedometer counts between normal
      weight and overweight or obese women during a walking and jogging activity.
AB  - This study compared energy expenditure (EE), economy of movement, and pedometer
      counts between normal weight and overweight or obese women during a treadmill
      walking and jogging activity. Participants were 13 normal weight (BMI 22.2 +/-
      2.0 kg m(-2)) and 13 overweight or obese (BMI 27.2 +/- 2.1 kg m(-2)) women and
      all were non-smokers, not regularly active, and able to run 1.609 km continuously
      at 2.23 m s(-1). Each participant reported to the laboratory on three separate
      days within a 1-week period. During the first visit, tests for resting metabolic
      rate via indirect calorimetry, anthropometric measures, and VO(2)max were
      completed. On the subsequent two visits, participants were randomized to perform
      either a 1.609-km walk at 1.34 m s(-1) or a 1.609-km jog at 2.23 m s(-1). During
      each physical activity trial, all participants wore a pedometer to assess steps
      taken. EE during the 1.609-km walk was 280 +/- 29 kJ for the normal weight and
      356 +/- 42 kJ for the overweight/obese women and during the 1.609-km jog was 393
      +/- 46 kJ for the normal weight and 490 +/- 59 kJ for the overweight/obese women.
      In both trials, EE was statistically greater in the overweight/obese women.
      Economy of movement was not statistically different between the normal weight and
      overweight/obese women during the walk or jog. In both groups, pedometer counts
      were lower during the jog than the walk (P < 0.05). These data indicate
      significant differences in EE between normal weight and overweight/obese women
      during both a walking and jogging activity.

PMID- 19408006
TI  - Parotidectomy: the timing of post-operative complications.
AB  - We evaluated the timing of complications following parotidectomy. We performed a
      119-patient retrospective case series analysis over a 12-year period (1994-2006)
      and investigated timing of post-operative complications. 38% of temporary facial
      nerve palsies resolved within 1 month, 78% within 3 months and all recorded
      resolved within 7 months. Tumour recurrence, ranged from 5 months to 9 years post
      surgery with a median of 5 years. Salivary fistula formation ranged from 3 to 45
      days post-surgery with a median of 11.5 days. The development of Frey's ranged
      from 20 days to 22 months, median 11 months. This information can better inform
      clinicians and those patients undergoing parotidectomy.

PMID- 19408008
TI  - Activity patterns in networks stabilized by background oscillations.
AB  - The brain operates in a highly oscillatory environment. We investigate here how
      such an oscillating background can create stable organized behavior in an array
      of neuro-oscillators that is not observable in the absence of oscillation, much
      like oscillating the support point of an inverted pendulum can stabilize its up
      position, which is unstable without the oscillation. We test this idea in an
      array of electronic circuits coming from neuroengineering: we show how the
      frequencies of the background oscillation create a partition of the state space
      into distinct basins of attraction. Thus, background signals can stabilize
      persistent activity that is otherwise not observable. This suggests that an
      image, represented as a stable firing pattern which is triggered by a voltage
      pulse and is sustained in synchrony or resonance with the background oscillation,
      can persist as a stable behavior long after the initial stimulus is removed. The
      background oscillations provide energy for organized behavior in the array, and
      these behaviors are categorized by the basins of attraction determined by the
      oscillation frequencies.

PMID- 19408009
TI  - Optimal motor control may mask sensory dynamics.
AB  - Properties of neural controllers for closed-loop sensorimotor behavior can be
      inferred with system identification. Under the standard paradigm, the closed-loop
      system is perturbed (input), measurements are taken (output), and the
      relationship between input and output reveals features of the system under study.
      Here we show that under common assumptions made about such systems (e.g. the
      system implements optimal control with a penalty on mechanical, but not sensory,
      states) important aspects of the neural controller (its zeros mask the modes of
      the sensors) remain hidden from standard system identification techniques. Only
      by perturbing or measuring the closed-loop system "between" the sensor and the
      control can these features be exposed with closed-loop system identification
      methods; while uncommon, there exist noninvasive techniques such as galvanic
      vestibular stimulation that perturb between sensor and controller in this way.

PMID- 19408011
TI  - Use of freeze-cracking in ontogenetic research in Macrostomum lignano
      (Macrostomida, Rhabditophora).
AB  - A method for studying whole mount flatworm embryos based on freeze-cracking of
      the eggs is described. This method allows successful immunohistological and
      immunocytological studies of whole mount embryos. It does not require the use of
      sharpened needles or a microinjection system to puncture the eggshell. Moreover,
      this method is more practical and less time-consuming than classical puncturing
      and much cheaper than the use of a microinjection system. The advantages of this
      method are illustrated by results of several immunolocalisation experiments in
      the macrostomid flatworm Macrostomum lignano. The optimal procedure and crucial
      steps for this method are discussed.

PMID- 19408010
TI  - Occurrence and environmental stress responses of two plastid terminal oxidases in
      Haematococcus pluvialis (Chlorophyceae).
AB  - The plastid terminal oxidase (PTOX) is a plastoquinol oxidase involved in
      carotenoid biosynthesis in higher plants, and may also represent the elusive
      oxidase in chlororespiration. Haematococcus pluvialis is a green alga that has
      the ability to synthesize and accumulate large amounts of the red carotenoid
      astaxanthin (ca. 2% of dry weight) under various stress conditions. However, the
      occurrence and function of PTOX in astaxanthin synthesis and the stress response
      in this organism is unknown. In this study, two ptox cDNAs were cloned and
      sequenced from H. pluvialis and were designated as ptox1 and ptox2. Genome
      sequence analysis and database searching revealed that duplication of PTOX gene
      occurred in certain eukaryotic algae, but not in cyanobacteria and higher plants.
      The physiological and biochemical evidence indicated that PTOX is involved in
      astaxanthin synthesis and plays a critical protective role against stress.
      Analysis of the transcriptional expression of the PTOXs and phytoene desaturase
      gene further suggests that it may be PTOX1 rather than PTOX2 that is co-regulated
      with astaxanthin synthesis. The fact that the changes in transcripts of ptoxs in
      response to high light and other stressors and the differential expression of
      ptox1 and ptox2, suggests that PTOX, coupled with astaxanthin synthesis pathway,
      exerts broad, yet undefined functions in addition to those identified in higher
      plants.

PMID- 19408012
TI  - A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial
      chemoembolization versus hepatectomy alone for Stage III A hepatocellular
      carcinoma.
AB  - PURPOSE: Hepatectomy is considered as the potentially curative treatment for
      hepatocellular carcinoma (HCC) and used in some selected Stage IIIA HCC, which
      include multiple tumors more than 5 cm or tumor involving a major branch of the
      portal or hepatic vein(s) (UICC TNM staging system, sixth edition). Transcatheter
      arterial chemoembolization (TACE) was used in retrospective studies to improve
      the survival outcome of resected HCC. However, its beneficial effect on the
      survival outcomes of the Stage IIIA patients has not been evaluated. The present
      study is to evaluate if hepatectomy combining with adjuvant TACE for Stage IIIA
      HCC result in better long-term survival outcome when compared with hepatectomy
      alone. METHODS: From January 2001 to March 2004, we conducted a prospective
      randomized trial in patients with Stage IIIA HCC (NCT00652587), recruiting 115
      Stage IIIA HCC patients to undergo hepatectomy with adjuvant TACE (HT arm) or to
      undergo hepatectomy alone (HA arm) in our cancer center. Survival outcomes of the
      two arms were analyzed. RESULTS: The demographic data were well matched between
      the two arms. There were no significant differences in the morbidity and in
      hospital mortality between the two arms of patients. The most significant
      toxicities associated with adjuvant TACE were nausea/vomiting (54.4%) and
      transient hepatic toxicity (elevation of aminotransferase, 52.6%). Although there
      was no significant difference in the rate of recurrence between the two arms
      (50/57 vs. 56/58, P = 0.094), HT arm seemed to have more proportion of single
      lesion of recurrent HCC (chi (2) = 3.719, P = 0.054) and more proportion of
      potential curative therapy for recurrence (chi (2) = 4.456, P = 0.035). Until the
      time of censor, 92 patients had died. The 1-, 3-, and 5-year overall survival
      rates and median overall survival for HT arm were 80.7, 33.3, 22.8% and 23.0
      months, respectively. The corresponding overall survival rates and median overall
      survival for HA arm were 56.5, 19.4, 17.5% and 14.0 months, respectively. The
      difference was significant (stratified log-rank test, P = 0.048). The 1-, 3-, and
      5-year disease-free survival rates and median disease-free survival for HT arm
      were 29.7, 9.3, 9.3% and 6.0 months, respectively; correspondingly, for HA arm
      were 14.0, 3.5, 1.7% and 4.0 months, respectively (stratified log-rank test, P =
      0.004). CONCLUSIONS: For Stage IIIA HCC, hepatectomy with adjuvant TACE
      efficaciously and safely improved survival outcomes when compared with
      hepatectomy alone.

PMID- 19408013
TI  - Strategies and issues in the detection of pathway enrichment in genome-wide
      association studies.
AB  - A fundamental question in human genetics is the degree to which the polygenic
      character of complex traits derives from polymorphism in genes with similar or
      with dissimilar functions. The many genome-wide association studies now being
      performed offer an opportunity to investigate this, and although early attempts
      are emerging, new tools and modeling strategies still need to be developed and
      deployed. Towards this goal, we implemented a new algorithm to facilitate the
      transition from genetic marker lists (principally those generated by PLINK) to
      pathway analyses of representational gene sets in either threshold or threshold
      free downstream applications (e.g. DAVID, GSEA-P, and Ingenuity Pathway
      Analysis). This was applied to several large genome-wide association studies
      covering diverse human traits that included type 2 diabetes, Crohn's disease, and
      plasma lipid levels. Validation of this approach was obtained for plasma HDL
      levels, where functional categories related to lipid metabolism emerged as the
      most significant in two independent studies. From analyses of these samples, we
      highlight and address numerous issues related to this strategy, including
      appropriate gene based correction statistics, the utility of imputed versus non
      imputed marker sets, and the apparent enrichment of pathways due solely to the
      positional clustering of functionally related genes. The latter in particular
      emphasizes the importance of studies that directly tie genetic variation to
      functional characteristics of specific genes. The software freely provided that
      we have called ProxyGeneLD may resolve an important bottleneck in pathway-based
      analyses of genome-wide association data. This has allowed us to identify at
      least one replicable case of pathway enrichment but also to highlight functional
      gene clustering as a potentially serious problem that may lead to spurious
      pathway findings if not corrected.

PMID- 19408014
TI  - Amylase expression in taste receptor cells of rat circumvallate papillae.
AB  - The chemical composition of the luminal content is now accepted to have a
      profound influence on the performance of chemosensory receptors. Gustatory and
      intestinal chemoreceptors have in common their expression of molecules involved
      in taste sensing and signal transduction pathways. The recent finding that
      enterocytes of the duodenal epithelium are capable of expressing luminal
      pancreatic amylase suggests that taste cells of the gustatory epithelium might,
      in the same way, express salivary amylase in the oral cavity. Therefore, we
      investigated amylase expression in rat circumvallate papillae by using analyses
      involving immunohistochemistry, Western blot, and reverse transcription with the
      polymerase chain reaction. In addition, we used double-labeling confocal laser
      microscopy to compare amylase immunolabeling with that of the following markers:
      protein gene product 9.5 (PGP 9.5) and chromogranin A (CgA) for endocrine cells,
      alpha-gustducin and phospholipase C beta 2 (PLC beta 2) as taste-signaling
      molecules, and cystic fibrosis transmembrane regulator (CFTR) and Clara-cell
      specific secretory protein of 10-kDa (CC10) as secretory markers. The results
      showed that amylase was present in some taste bud cells; its immunoreactivity was
      observed in subsets of cells that expressed CgA, alpha-gustducin, PLC beta 2,
      CFTR, or CC10. PGP 9.5 immunoreactivity was never colocalized with amylase. The
      data suggest that amylase-positive cells constitute an additional subset of taste
      receptor cells also associated with chemoreceptorial and/or secretory molecules,
      confirming the occurrence of various pathways in taste buds.

PMID- 19408015
TI  - Localization patterns of fibroblast growth factor 1 and its receptors FGFR1 and
      FGFR2 in postnatal mouse retina.
AB  - Fibroblast growth factors (FGFs) exert basic functions both during embryonic
      development and in the adult. The expression of FGFs and their receptors has been
      reported in mammalian retinas, although information on the organization of the
      FGF system is still incomplete. Here, we report a detailed double-label
      immunohistochemical investigation of the localization patterns of FGF1 and its
      receptors FGFR1 and FGFR2 in adult and early postnatal mouse retinas. In adult
      retinas, FGF1 is localized to ganglion cells, horizontal cells, and photoreceptor
      inner and outer segments. FGFR1 is found in ganglion cells and Muller cells,
      whereas FGFR2 is primarily located in ganglion cells, the nuclei of Muller cells,
      and glycine-containing amacrine cells. During postnatal development, the patterns
      of FGF1, FGFR1, and FGFR2 immunostaining are similar to those in the adult,
      although transient FGF1-expressing cells have been detected in the proximal inner
      nuclear layer before eye opening. These patterns are consistent with a major
      involvement of FGF1, FGFR1, and FGFR2 in ganglion cell maturation (during
      development) and survival (in the adult). Moreover, FGF1 may affect amacrine cell
      development, whereas Muller cells appear to be regulated via both FGFR1 and FGFR2
      throughout postnatal life. In immature retinas, large numbers of amacrine cells,
      including those containing calbindin and glycine, display both FGF1 and FGFR2
      immunoreactivities in their nuclei, suggesting an action of FGF1 on FGFR2 leading
      to the maturation of these amacrine cells during a restricted period of postnatal
      development.

PMID- 19408016
TI  - Arbuscular mycorrhizal fungal species suppress inducible plant responses and
      alter defensive strategies following herbivory.
AB  - In a greenhouse experiment using Plantago lanceolata, plants grown with different
      arbuscular mycorrhizal (AM) fungal species differed in constitutive levels of
      chemical defense depending on the species of AM fungi with which they were
      associated. AM fungal inoculation also modified the induced chemical response
      following herbivory by the specialist lepidopoteran herbivore Junonia coenia, and
      fungal species varied in how they affected induced responses. On average,
      inoculation with AM fungi substantially reduced the induced chemical response as
      compared with sterile controls, and inoculation with a mixture of AM fungi
      suppressed the induced response of P. lanceolata to herbivory. These results
      suggest that AM fungi can exert controlling influence over plant defensive
      phenotypes, and a portion of the substantial variation among experimental tests
      of induced chemical responses may be attributable to AM fungi.

PMID- 19408017
TI  - Mathematical modeling of maltose hydrolysis in different types of reactor.
AB  - A commercial enzyme Dextrozyme was tested as catalyst for maltose hydrolysis at
      two different temperatures: 40 and 65 degrees C at pH 5.5. Its operational
      stability was studied in different reactor types: batch, repetitive batch, fed
      batch and continuously operated enzyme membrane reactor. Dextrozyme was more
      active at 65 degrees C, but operational stability decay was observed during the
      prolonged use in the reactor at this temperature. The reactor efficiencies were
      compared according to the volumetric productivity, biocatalyst productivity and
      enzyme consumption. The best reactor type according to the volumetric
      productivity for maltose hydrolysis is batch and the best reactor type according
      to the biocatalyst productivity and enzyme consumption is continuously operated
      enzyme membrane reactor. The mathematical model developed for the maltose
      hydrolysis in the different reactors was validated by the experiments at both
      temperatures. The Michaelis-Menten kinetics describing maltose hydrolysis was
      used.

PMID- 19408018
TI  - The contribution of RCTs to quality management and their feasibility in practice.
AB  - The randomized controlled trial (RCT) is generally accepted as the most reliable
      method of conducting clinical research. To obtain an unbiased evaluation of the
      effectiveness of spine surgery, patients should be randomly assigned to either
      new or standard treatment. The aim of the present article is to provide a short
      overview of the advantages and challenges of RCTs and to present a summary of the
      conclusions of the Cochrane Reviews in spine surgery and later published trials
      in order to evaluate their contribution to quality management and feasibility in
      practice. From the searches, 130 RCTs were included, 95 from Cochrane Reviews and
      systematic reviews, and 35 from additional search. No study comparing surgery
      with sham surgery was identified. The first RCT in spine surgery was published in
      1974 and compared debridement and ambulatory treatment in tuberculosis of the
      spine. The contribution of RCTs in spinal surgery has markedly increased over the
      last 10 years, which indicates that RCTs are feasible in this field. The results
      demonstrate missing quality specifications. Despite the number of published
      trials there is conflicting or limited evidence to support various techniques of
      instrumentation. The only intervention that receives strong evidence is
      discectomy for faster relief in carefully selected patients due to lumbar disc
      prolapse with sciatica. For future trials, authors, referees, and editors are
      recommended to follow the CONSORT statement. RCTs provide evidence to support
      clinical opinions before implementation of new techniques, but the individual
      clinical experience is still important for the doctor who has to face the
      patient.

PMID- 19408019
TI  - A graph theoretical approach for assessing bio-macromolecular complex structural
      stability.
AB  - Fast and proper assessment of bio macro-molecular complex structural rigidity as
      a measure of structural stability can be useful in systematic studies to predict
      molecular function, and can also enable the design of rapid scoring functions to
      rank automatically generated bio-molecular complexes. Based on the graph
      theoretical approach of Jacobs et al. [Jacobs DJ, Rader AJ, Kuhn LA, Thorpe MF
      (2001) Protein flexibility predictions using graph theory. Proteins: Struct Funct
      Genet 44:150-165] for expressing molecular flexibility, we propose a new scheme
      to analyze the structural stability of bio-molecular complexes. This analysis is
      performed in terms of the identification in interacting subunits of clusters of
      flappy amino acids (those constituting regions of potential internal motion) that
      undergo an increase in rigidity at complex formation. Gains in structural
      rigidity of the interacting subunits upon bio-molecular complex formation can be
      evaluated by expansion of the network of intra-molecular inter-atomic
      interactions to include inter-molecular inter-atomic interaction terms. We
      propose two indices for quantifying this change: one local, which can express
      localized (at the amino acid level) structural rigidity, the other global to
      express overall structural stability for the complex. The new system is validated
      with a series of protein complex structures reported in the protein data bank.
      Finally, the indices are used as scoring coefficients to rank automatically
      generated protein complex decoys.

PMID- 19408021
TI  - Effects of magnesium salt concentrations on B-DNA overstretching transition.
AB  - In this study, we use optical tweezers to investigate the ionic effects of
      magnesium salt solutions on the overstretching transition of single B-DNA
      molecules. The experimental data are compared with those in sodium salt
      solutions. The overstretching transition force increases when the NaCl or MgCl(2)
      salt concentration increases. Magnesium cations have much stronger effects on the
      overstretching transition force than sodium cations. For both NaCl and MgCl(2)
      salt solutions, the overstretching transition force is linear with the natural
      logarithm of salt concentration, which confirms the theory proposed in previous
      paper. The modified ZZO model is applied to study the electrostatic contribution
      of magnesium salt solutions to the overstretching transition of single B-DNA
      molecules. The consistency between the experimental data and analytical results
      shows that the modified ZZO model can simulate the transition behavior of single
      B-DNA molecules in different NaCl and MgCl(2) salt solutions.

PMID- 19408020
TI  - Extended endoscopic approaches for midline skull-base lesions.
AB  - The endoscopic transsphenoidal approach has been reported in the literature as a
      useful tool to treat sellar and parasellar lesions. The endoscope permits a
      panoramic view instead of the narrow microscopic view, and it allows the
      inspection and removal of the lesions of sellar, parasellar, and suprasellar
      compartments by angled-lens endoscopes. On the basis of the experience gained
      with the use of the endoscope, we have performed extended endoscopic endonasal
      transsphenoidal approach in 13 of 200 (total endoscopic transphenoidal approaches
      since September 1997) patients for the last 5 years. Extended endoscopic
      transsphenoidal approach was performed for three patients with pituitary adenoma,
      two patients with craniopharyngioma, one patient with metastatic lesion, one
      patient with anaplastic germinoma, two patients with chordoma, one patient with
      chondrosarcoma, one plasmocytoma, and two patients with tuberculum sella
      meningioma. Total removal of the tumor was achieved in nine patients and subtotal
      removal was achieved in four patients. Extended approaches are essential for
      reaching the area from lamina cribrosa to the cranio-cervical junction.
      Endoscopic approach permits reaching the lesion without brain retraction and with
      minimal neurovascular manipulation. The main problems are related to the
      hemorrhage control of intracranial vessels and to the closure of the dural and
      bony defects, with subsequent increased risk of postoperative cerebrospinal fluid
      leak, tensive pneumocephalus, and/or meningitis.

PMID- 19408022
TI  - Correlation effects, image charge effects and finite size in the macro-ion
      electrolyte system: a field-theoretic approach.
AB  - We consider a model of a macro-ion surrounded by small ions of an electrolyte
      solution. The finite size of ionic charge distributions of ions, and image charge
      effects are considered. From such a model it is possible to construct a
      statistical field theory with a single fluctuating field and derive physical
      interpretations for both the mean field and two-point correlation function. For
      point-like charges, at the level of a Gaussian (or saddle point) approximation,
      we recover the standard Poisson-Boltzmann equation. However, to include ionic
      correlation effects, as well as image charge effects of individual ions, we must
      go beyond this. From the field theory considered, it is possible to construct
      self-consistent approximations. We consider the simplest of these, namely the
      Hartree approximation. The Hartree equations take the form of two coupled
      equations. One is a modified Poisson-Boltzmann equation; the other describes both
      image charge effects on the individual ions, as well as correlations. Such
      equations are difficult to solve numerically, so we develop an (a WKB-like)
      approximation for obtaining approximate solutions. This, we apply to a uniformly
      charged rod in univalent electrolyte solution, for point like ions, as well as
      for extended spherically symmetric distributions of ionic charge on electrolyte
      ions. The solutions show how correlation effects and image charge effects modify
      the Poisson-Boltzmann result. Finite-size charge distributions of the ions reduce
      both the effects of correlations and image charge effects. For point charges, we
      test the WKB approximation by calculating a leading-order correction from the
      exact Hartree result, showing that the WKB-like approximation works reasonably
      well in describing the full solution to the Hartree equations. From these
      solutions, we also calculate an effective charge compensation parameter in an
      analytical formula for the interaction of two charged cylinders.

PMID- 19408024
TI  - Continuous acetone-butanol-ethanol production by corn stalk immobilized cells.
AB  - Corn stalk was used as a support to immobilize Clostridia beijerinckii ATCC 55025
      in the fermentation process of acetone, butanol, and ethanol production. The
      effect of the dilution rate on solvent production was examined in a steady-state
      20-day continuous flow operation. The maximum total solvent concentration of 8.99
      g l(-1) was obtained at a dilution rate of 0.2 h(-1). Increasing the dilution
      rate between 0.2 and 1.0 h(-1) resulted in an increased solvent productivity, and
      the highest solvent productivity was obtained at 5.06 g l(-1) h(-1) with a
      dilution rate of 1 h(-1). The maximum solvent yield from glucose of 0.32 g g(-1)
      was observed at 0.25 h(-1). The cell adsorption and morphology change during the
      growth on corn stalk support were examined by the SEM.

PMID- 19408023
TI  - Acoustic radiation force on an air bubble and soft fluid spheres in ideal
      liquids: example of a high-order Bessel beam of quasi-standing waves.
AB  - The partial wave series for the scattering of a high-order Bessel beam (HOBB) of
      acoustic quasi-standing waves by an air bubble and fluid spheres immersed in
      water and centered on the axis of the beam is applied to the calculation of the
      acoustic radiation force. A HOBB refers to a type of beam having an axial
      amplitude null and an azimuthal phase gradient. Radiation force examples obtained
      through numerical evaluation of the radiation force function are computed for an
      air bubble, a hexane, a red blood and mercury fluid spheres in water. The
      examples were selected to illustrate conditions having progressive, standing and
      quasi-standing waves with appropriate selection of the waves' amplitude ratio. An
      especially noteworthy result is the lack of a specific vibrational mode
      contribution to the radiation force determined by appropriate selection of the
      HOBB parameters.

PMID- 19408025
TI  - Functional expression of SCO7832 stimulates tautomycetin production via pathway
      specific regulatory gene overexpression in Streptomyces sp. CK4412.
AB  - Comparative transcriptome analysis has revealed several acidic pH shock-induced
      genes presumably involved with stimulation of antibiotic production by S.
      coelicolor (Kim et al. Appl Microbiol Biotechnol 2007). Streptomyces sp. CK4412
      produces a novel T cell-specific immunosuppressive compound, tautomycetin (TMC).
      When cultured at acidic pH medium, it also exhibited higher TMC productivity. To
      verify a gene responsible for acidic pH shock-induced TMC stimulation, a putative
      acid-shock-induced gene, SCO7832 encoding an Na(+)/H(+) antiporter protein, was
      cloned under the influence of a strong constitutive ermE* promoter in an
      integrative expression pSET152 vector. This was followed by its conjugation into
      the TMC-producing Streptomyces sp. CK4412. Comparing TMC production and
      antifungal activity of wild-type and the SCO7832-containing exconjugant revealed
      that SCO7832 stimulated TMC production more than 3.5-fold in Streptomyces sp.
      CK4412. The over-expression of SCO7832 did not affect the ratio between intra-
      and extra-cellular TMC productions. However, it significantly stimulated the
      expression of a TMC-specific positive regulatory gene. This implies that the
      stimulatory effect of SCO7832 functions in TMC-producing Streptomyces sp. CK4412
      via up-regulation of a TMC pathway-specific positive regulatory gene, tmcN
      overexpression.

PMID- 19408026
TI  - Production of rosamicin derivatives in Micromonospora rosaria by introduction of
      D-mycinose biosynthetic gene with PhiC31-derived integration vector pSET152.
AB  - Some of the polyketide-derived bioactive compounds contain sugars attached to the
      aglycone core, and these sugars often impart specific biological activity to the
      molecule or enhance this activity. Mycinamicin II, a 16-member macrolide
      antibiotic produced by Micromonospora griseorubida A11725, contains a branched
      lactone and two different deoxyhexose sugars, D-desosamine and D-mycinose, at the
      C-5 and C-21 positions, respectively. The D-mycinose biosynthesis genes, mycCI,
      mycCII, mycD, mycE, mycF, mydH, and mydI, present in the M. griseorubida A11725
      chromosome were introduced into pSET152 under the regulation of the promoter of
      the apramycin-resistance gene aac(3)IV. The resulting plasmid pSETmycinose was
      introduced into Micromonospora rosaria IFO13697 cells, which produce the 16
      membered macrolide antibiotic rosamicin containing a branched lactone and D
      desosamine at the C-5 position. Although the M. rosaria TPMA0001 transconjugant
      exhibited low rosamicin productivity, two new compounds, IZI and IZII, were
      detected in the ethylacetate extract from the culture broth. IZI was identified
      as a mycinosyl rosamicin derivative, 23-O-mycinosyl-20-deoxo-20-dihydro-12,13
      deepoxyrosamicin (MW 741), which has previously been synthesized by a
      bioconversion technique. This is the first report on production of mycinosyl
      rosamicin-derivatives by a engineered biosynthesis approach. The integration site
      PhiC31attB was identified on M. rosaria IFO13697 chromosome, and the site lay
      within an ORF coding a pirin homolog protein. The pSETmycinose could be useful
      for stimulating the production of "unnatural" natural mycinosyl compounds by
      various actinomycete strains using the bacteriophage PhiC31 att/int system.

PMID- 19408027
TI  - Strain improvement of Sporosarcina pasteurii for enhanced urease and calcite
      production.
AB  - Phenotypic mutants of Sporosarcina pasteurii (previously known as Bacillus
      pasteurii) (MTCC 1761) were developed by UV irradiation to test their ability to
      enhance urease activity and calcite production. Among the mutants, Bp M-3 was
      found to be more efficient compared to other mutants and wild-type strain. It
      produced the highest urease activity and calcite production compared to other
      isolates. The production of extracellular polymeric substances and biofilm was
      also higher in this mutant than other isolates. Microbial sand plugging results
      showed the highest calcite precipitation by Bp M-3 mutant. Scanning electron
      micrography, energy-dispersive X-ray and X-ray diffraction analyses evidenced the
      direct involvement of bacteria in CaCO3 precipitation. This study suggests that
      calcite production by the mutant through biomineralization processes is highly
      effective and may provide a useful strategy as a sealing agent for filling the
      gaps or cracks and fissures in any construction structures.

PMID- 19408028
TI  - Double deletion of dtsR1 and pyc induce efficient L: -glutamate overproduction in
      Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum strains are used for the fermentative production of L
      glutamate. Five C. glutamicum deletion mutants were isolated by two rounds of
      selection for homologous recombination and identified by Southern blot analysis.
      The growth, glucose consumption and glutamate production of the mutants were
      analyzed and compared with the wild-type ATCC 13032 strain. Double disruption of
      dtsR1 (encoding a subunit of acetyl-CoA carboxylase complex) and pyc (encoding
      pyruvate carboxylase) caused efficient overproduction of L-glutamate in C.
      glutamicum; production was much higher than that of the wild-type strain and
      DeltadtsR1 strain under glutamate-inducing conditions. In the absence of any
      inducing conditions, the amount of glutamate produced by the double-deletion
      strain DeltadtsR1Deltapyc was more than that of the mutant DeltadtsR1. The
      activity of phosphoenolpyruvate carboxylase (PEPC) was found to be higher in the
      DeltadtsR1Deltapyc strain than in the DeltadtsR1 strain and the wild-type strain.
      Therefore, PEPC appears to be an important anaplerotic enzyme for glutamate
      synthesis in DeltadtsR1 derivatives. Moreover, this conclusion was confirmed by
      overexpression of ppc and pyc in the two double-deletion strains
      (DeltadtsR1Deltappc and DeltadtsR1Deltapyc), respectively. Based on the data
      generated in this investigation, we suggest a new method that will improve
      glutamate production strains and provide a better understanding of the
      interaction(s) between the anaplerotic pathway and fatty acid synthesis.

PMID- 19408029
TI  - Accuracy of autotitrating CPAP to estimate the residual Apnea-Hypopnea Index in
      patients with obstructive sleep apnea on treatment with autotitrating CPAP.
AB  - OBJECTIVE: Autotitrating continuous positive airway pressure (auto-CPAP) devices
      now have a smart card (a pocket-sized card with embedded integrated circuits
      which records data from the CPAP machine such as CPAP usage, CPAP pressure, large
      leak, etc.) which can estimate the Apnea-Hypopnea Index (AHI) on therapy. The aim
      of this study was to determine the accuracy of auto-CPAP in estimating the
      residual AHI in patients with obstructive sleep apnea (OSA) who were treated with
      auto-CPAP without a CPAP titration study. PATIENTS AND METHODS: We studied 99
      patients with OSA from April 2005 to May 2007 who underwent a repeat sleep study
      using auto-CPAP. The estimated AHI from auto-CPAP was compared with the AHI from
      an overnight polysomnogram (PSG) on auto-CPAP using Bland-Altman plot and
      likelihood ratio analyses. A PSG AHI cutoff of five events per hour was used to
      differentiate patients optimally treated with auto-CPAP from those with residual
      OSA on therapy. RESULTS: Bland and Altman analysis showed good agreement between
      auto-CPAP AHI and PSG AHI. There was no significant bias when smart card
      estimates of AHI at home were compared to smart card estimates obtained in the
      sleep laboratory. An auto-CPAP cutoff for the AHI of six events per hour was
      shown to be optimal for differentiating patients with and without residual OSA
      with a sensitivity of 0.92 (95% confidence interval (CI) 0.76 to 0.98) and
      specificity of 0.90 (95% CI 0.82 to 0.95) with a positive likelihood ratio (LR)
      of 9.6 (95% CI 5.1 to 21.5) and a negative likelihood ratio of 0.085 (95% CI 0.02
      to 0.25). Auto-CPAP AHI of eight events per hour yielded the optimal sensitivity
      (0.94, 95% CI 0.73 to 0.99) and specificity (0.90, 95% CI 0.82 to 0.95) with a
      positive LR of 9.6 (95% CI 5.23 to 20.31) and a negative LR of 0.065 (95% CI
      0.004 to 0.279) to identify patients with a PSG AHI of > or = 10 events per hour.
      CONCLUSION: Auto-CPAP estimate of AHI may be used to estimate residual AHI in
      patients with OSA of varying severity treated with auto-CPAP.

PMID- 19408030
TI  - Refixation stability in shoulder hemiarthroplasty in case of four-part proximal
      humeral fracture.
AB  - Primary stability of refixated fractures in case of shoulder hemiarthroplasty is
      a prerequisite to restore physiological glenohumeral joint function. Clinical
      observations often show a secondary dislocation and subsequent resorption of the
      bony anchor points like the greater and lesser tuberosity at the rotator cuff
      tendons. This failed integration leads to impaired glenohumeral load transmission
      and subsequent reduction of mobility. As a consequence, the optimisation of
      refixation methods is crucial for a better clinical outcome. To prove the
      stability of refixation techniques, a Finite Element fracture model was built.
      Resulting stresses at the bone surface and fragment migration relative to the
      prosthesis shaft were studied. The results of the calculations show that the
      isolated tuberosities show unstressed bone regions compared to the intact model.
      This circumstance may explain the clinically detected bone resorption due to the
      absence of mechanical stimuli. Furthermore, a cable guidance through lateral
      holes in the middle part of the proximal prosthesis results in a lower fragment
      displacement than a circumferential fixation method surrounding the entire
      proximal bone.

PMID- 19408032
TI  - Owner controlled data exchange in nutrigenomic collaborations: the NuGO
      information network.
AB  - New 'omics' technologies are changing nutritional sciences research. They enable
      to tackle increasingly complex questions but also increase the need for
      collaboration between research groups. An important challenge for successful
      collaboration is the management and structured exchange of information that
      accompanies data-intense technologies. NuGO, the European Nutrigenomics
      Organization, the major collaborating network in molecular nutritional sciences,
      is supporting the application of modern information technologies in this area. We
      have developed and implemented a concept for data management and computing
      infrastructure that supports collaboration between nutrigenomics researchers. The
      system fills the gap between "private" storing with occasional file sharing by
      email and the use of centralized databases. It provides flexible tools to share
      data, also during experiments, while preserving ownership. The NuGO Information
      Network is a decentral, distributed system for data exchange based on standard
      web technology. Secure access to data, maintained by the individual researcher,
      is enabled by web services based on the the BioMoby framework. A central
      directory provides information about available web services. The flexibility of
      the infrastructure allows a wide variety of services for data processing and
      integration by combining several web services, including public services.
      Therefore, this integrated information system is suited for other research
      collaborations.

PMID- 19408031
TI  - Common variants of ABCB4 and ABCB11 and plasma lipid levels: a study in sib pairs
      with gallstones, and controls.
AB  - Most epidemiological surveys have confirmed the association of low HDL
      cholesterol and high triglyceride levels with cholesterol gallstones. Our
      objective was to analyze the relationship between plasma lipid levels and common
      polymorphisms of ABCB11 (encoding the bile salt export pump, BSEP) and ABCB4
      (encoding the phospholipid transporter into bile, MDR3) genes. Plasma lipids were
      measured in 108 index patients of sib pairs with gallstones and in 260 controls.
      Using PCR-based assays with 5'-nuclease and fluorescence detection (TaqMan), the
      ABCB11 coding SNP p.A444V and four haplotype-tagging SNPs covering the ABCB4 gene
      (c.504C > T, c.711T > A, p.R652G, rs31653 in intron 26) were genotyped. Plasma
      lipids were compared in carriers of the common versus rare allele of these
      polymorphisms using Student's t test and Pearson's correlation. BMI and
      triglyceride levels were higher and HDL-cholesterol levels were lower in affected
      siblings than in controls. Among cases, triglyceride and cholesterol levels were
      higher in carriers of the common versus rare (hetero/homozygous carriers) allele
      of the SNPs p.A444V of ABCB11 and C.504C > T of ABCB4. HDL-cholesterol was lower
      in carriers of the common allele of rs31653. In controls, significant differences
      of cholesterol and HDL-cholesterol levels were found in carriers of ABCB4
      polymorphisms. Our results do not support the hypothesis of a link between ABCB4
      and ABCB11 polymorphisms, lithogenic dyslipidemia, and gallstone risk.

PMID- 19408033
TI  - Variation in protein levels obtained from human blood cells and biofluids for
      platelet, peripheral blood mononuclear cell, plasma, urine and saliva proteomics.
AB  - Blood cells and biofluid proteomics are emerging as a valuable tool to assess
      effects of interventions on health and disease. This study is aimed to assess the
      amount and variability of proteins from platelets, peripheral blood mononuclear
      cells (PBMC), plasma, urine and saliva from ten healthy volunteers for proteomics
      analysis, and whether protein yield is affected by prolonged fasting. Volunteers
      provided blood, saliva and morning urine samples once a week for 4 weeks after an
      overnight fast. Volunteers were fasted for a further 24 h after the fourth
      sampling before providing their final samples. Each 10 mL whole blood provided
      400-1,500 mug protein from platelets, and 100-600 mug from PBMC. 30 muL plasma
      depleted of albumin and IgG provided 350-650 mug protein. A sample of morning
      urine provided 0.9-8.6 mg protein/dL, and a sample of saliva provided 70-950 mug
      protein/mL. None of these yields were influenced by the degree of fasting
      (overnight or 36 h). In conclusion, in contrast to the yields from plasma,
      platelets and PBMC, the protein yields of urine and saliva samples were highly
      variable within and between subjects. Certain disease conditions may cause higher
      or lower PBMC counts and thus protein yields, or increased urinary protein
      levels.

PMID- 19408037
TI  - Healing process after surgical treatment with scalpel, electrocautery and laser
      radiation: histomorphologic and histomorphometric analysis.
AB  - The aim of this study was to evaluate and compare the healing process after
      surgical treatment of chemically induced lesions in the lateral edge of tongue of
      hamsters performed with scalpel, electrocautery, carbon dioxide (CO(2)) laser
      radiation or neodymium:yttrium-aluminum-garnet (Nd:YAG) laser radiation. Eighty
      hamsters of both sexes were used and examined at postoperative days 7, 14, 21 and
      28 by histological and histomorphometric analysis of the skeletal muscle fibers.
      In the histological analysis it was observed that the dynamics of the healing
      process was faster in the group treated by scalpel than in the other groups. The
      histomorphometric observation of the skeletal muscle fibers was submitted to one
      way analysis of variance (ANOVA) and Tukey's multiple comparison test, with a
      level of significance set at P < 0.05, which showed that the amount of skeletal
      muscle fiber formed had significantly increased in the group treated by scalpel
      in comparison with that in the groups treated by electrocautery (P < 0.01), CO(2)
      laser irradiation (P < 0.001) and Nd:YAG laser irradiation (P < 0.01) on the 14th
      postoperative day. A gradual increase in skeletal muscle fibers formed during the
      healing process was observed in all groups. When the laser irradiated groups were
      compared, it was possible to conclude that tissue organization and
      vascularization were faster and more intense in the Nd:YAG laser irradiated group
      than in the CO(2) laser irradiated group.

PMID- 19408036
TI  - Efficacy of an Andrographis paniculata composition for the relief of rheumatoid
      arthritis symptoms: a prospective randomized placebo-controlled trial.
AB  - Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) possesses anti
      inflammatory effects, attributed to the main constituent andrographolide proposed
      as alternative in the treatment of autoimmune disease. A prospective, randomized,
      double blind, and placebo-controlled study in patients with rheumatoid arthritis
      (RA) was performed. Tablets (Paractin) made of an extract of A. paniculata (30%
      total andrographolides) were administered three times a day for 14 weeks, after a
      2-week washout period to 60 patients with active RA. The primary outcomes were
      pain intensity measured using a horizontal visual analog pain scale (VAPS). In
      addition, ACR, EULAR, and SF36 clinical parameters were recorded. The intensity
      of joint pain decreased in the active vs placebo group at the end of treatment,
      although these differences were not statistically significant. A significant
      diminishing for week in tender joint -0.13 95% confidence interval (CI; -0.22 to
      0.06; p = 0.001), number of swollen joints -0.15 95%CI (-0.29 to -0.02; p =
      0.02), total grade of swollen joint -0.27 95%CI (-0.48 to -0.07; p = 0.010),
      number of tender joints -0.25 95%CI (-0.48 to -0.02; p = 0.033), total grade of
      swollen joints -0.27 95%CI (-0.48 to -0.07; p = 0.01), total grade of tender
      joints -0.47 95%CI (-0.77 to -0.17; p = 0.002) and HAQ -0.52 95%CI (-0.82 to 
      0.21; p < 0.001) and SF36 0.02 95%CI (0.01 to 0.02; p < 0.001) health
      questionnaires was observed within the group with the active drug. Moreover, it
      was associated to a reduction of rheumatoid factor, IgA, and C4. These findings
      suggest that A. paniculata could be a useful "natural complement" in the
      treatment of AR; however, a larger trial and a more extended period of treatment
      is necessary in order to corroborate these results.

PMID- 19408039
TI  - Surgical tourism and the globalisation of healthcare.

PMID- 19408038
TI  - Photodynamic therapy for the treatment of buccal candidiasis in rats.
AB  - The study objective was to evaluate the effects of photodynamic therapy on buccal
      candidiasis in rats. After experimental candidiasis had been induced on the
      tongue dorsum, 72 rats were distributed into four groups according to treatment:
      treated with laser and methylene blue photosensitizer (L+P+); treated only with
      laser (L+P-); treated only with photosensitizer (L--P+); not treated with laser
      or photosensitizer (L-P-). The rats were killed immediately, 1 day, or 5 days
      after treatment, for microscopic analysis of the tongue dorsum. Observation
      verified that the photodynamic therapy group (L+P+) exhibited fewer epithelial
      alterations and a lower chronic inflammatory response than the L-P- group. The
      group L+P- presented more intense epithelial alterations and chronic inflammatory
      response than the remaining groups. The L-P+ group showed tissue lesions similar
      to those of the L-P- group. In conclusion, rats treated with photodynamic therapy
      developed more discrete candidiasis lesions than did the remaining groups.

PMID- 19408040
TI  - Imported childhood malaria: the Dublin experience, 1999-2006.
AB  - AIMS: Imported childhood malaria has never been studied in Ireland. We aimed to
      document the incidence and species of malaria in children presenting to
      paediatric hospitals in Dublin and to examine management and outcome measures.
      METHODS: Subjects were identified through laboratory archives from the three
      paediatric hospitals in Dublin. Clinical data were extracted retrospectively from
      clinical and laboratory records. RESULTS: As much as 67 episodes of malaria
      occurred in 66 children. Episodes occurred among new immigrants (n = 31) and
      Irish residents (n = 33) who travelled to endemic regions. The majority of those
      who travelled to endemic regions did not receive appropriate prophylaxis.
      Plasmodium falciparum was identified in 64 (95%) episodes, 26 with a parasite
      load above 2%. Eighteen children developed complications. All cases were treated
      successfully. CONCLUSIONS: Irish health-care practitioners need to encourage
      malaria prophylaxis among travellers to malaria-endemic regions. Management
      guidelines should be formulated to assist Irish clinicians treating this
      potentially fatal illness.

PMID- 19408041
TI  - Screening for developmental dysplasia of the hip: current practices in Ireland.
AB  - OBJECTIVE: To ascertain the current approach to screen for developmental
      dysplasia of the hip in the Republic of Ireland. METHODS: Two-pronged prospective
      and retrospective study. (1) Postal questionnaire to consultant paediatricians
      responsible for the routine neonatal care of infants in the Irish Republic in
      June 2006. (2) Retrospective database review to identify infants undergoing
      radiological follow-up and their outcome. RESULTS: All maternity units surveyed
      responded. Most units (84%) were dependent on radiographs at 4-6 months for
      imaging hips, only two units primarily used ultrasound (10.5%). We estimate that
      neonatal hip examination is performed by an experienced examiner in less than 30%
      of routine newborn examinations. On retrospective analysis, 94% of radiographs
      performed were normal. CONCLUSIONS: The most effective interventions, selective
      ultrasound and examination by an experienced clinician are not widely practiced.
      There is a need for the development of national guidelines based on available
      resources.

PMID- 19408042
TI  - Can we reduce preventable heart failure readmissions in patients enrolled in a
      Disease Management Programme?
AB  - BACKGROUND: Disease Management Programmes (DMPs) are successful in reducing
      hospital readmissions in heart failure (HF). However, there remain a number of
      patients enrolled in a DMP who are readmitted with HF. The primary aim of the
      study was to determine the proportion of preventable readmissions (PR). The
      secondary aim was to recognise patient characteristics which would identify
      certain patients at risk of having a PR. METHODS: A retrospective chart search
      was performed on patients readmitted over a 1-year period. RESULTS: 38.5% of
      readmissions were classified as PR. None of these patients made prior contact
      with the DMP. Admission levels of BNP, potassium, urea and creatinine were
      significantly lower in the PR group. CONCLUSION: DMP have proven benefits in
      reducing hospital readmission nonetheless a significant proportion of these
      readmissions are preventable. Further work is required to prospectively analyse
      why these patients fail to contact the DMP.

PMID- 19408043
TI  - The importance of distinguishing mucinous and nonmucinous bronchioloalveolar
      carcinomas.

PMID- 19408045
TI  - Pathological diagnosis and cytoreduction of cardiophrenic lymph node and pleural
      metastasis in ovarian cancer patients using video-assisted thoracic surgery.
AB  - BACKGROUND: The aim of this study was to assess the benefit of video-assisted
      thoracic surgery (VATS) in pathological diagnosis and intrathoracic cytoreduction
      of cardiophrenic lymph node (CPLN) and pleural metastasis on computed tomography
      (CT) in patients with ovarian cancer. METHODS: We reviewed a database of ovarian
      cancer patients who underwent VATS from June 2007 to November 2008. The criterion
      for suspicion of malignancy on CT was either a CPLN with short-axis dimension >5
      mm or multinodular pleural thickening. Seven patients with primary ovarian cancer
      and five patients with recurrent ovarian cancer were identified and evaluated.
      RESULTS: Twelve patients met the criterion for suspicious malignancy on CT, with
      CPLN metastasis and pleural metastasis in nine and five patients, respectively.
      CPLN metastasis was identified in two of four patients with primary ovarian
      cancer and in all five patients with recurrent ovarian cancer who had CPLN >5 mm
      on CT. Pleural metastasis was identified in three of five patients with
      suspicious pleural metastasis and in one of seven patients without suspicious
      pleural metastasis on preoperative CT. The median operation time for VATS was 65
      min and estimated blood loss was less than 20 ml in all cases. All visible
      intrathoracic diseases were completely resected without major complications, and
      VATS did not delay planned treatment. CONCLUSION: VATS enables the accurate
      pathological diagnosis and intrathoracic resection of pleural and CPLN metastasis
      in patients with ovarian cancer with acceptable morbidity. Further studies are
      needed to confirm the impact of VATS on survival in patients with ovarian cancer.

PMID- 19408044
TI  - Aggregation pheromone of the Qinghai spruce bark beetle, Ips nitidus eggers.
AB  - Volatiles from hindgut extracts of males of the Qinghai spruce bark beetle, Ips
      nitidus, from different attack phases (phase 1: unpaired males and phases 2-4:
      males joined with one to three females) and hindgut extracts of mated females
      were analyzed by gas chromatography-mass spectrometry (GC-MS)/flame ionization
      detection (FID) with both polar and enantioselective columns. The GC-MS/FID
      analyses demonstrated that unpaired males from attack phase 1 (nuptial chamber
      constructed) produced 2-methyl-3-buten-2-ol, approx. 74%-(-)-ipsdienol, and (-)
      cis-verbenol as major hindgut components, and (-)-trans-verbenol, (-)-ipsenol, (
      )-verbenone, myrtenol, and 2-phenylethanol as minor or trace components. The
      quantities of 2-methyl-3-buten-2-ol and especially ipsdienol decreased after
      mating during phases 2-4, whereas the quantities of (-)-cis- and (-)-trans
      verbenol did not change. In contrast, the quantity of (-)-ipsenol seemed to
      increase as mating activity progressed. After mating with three females (harem
      size = 3; phase 4), only trace to small amounts of male-specific compounds were
      detected from I. nitidus male hindguts. Chemical analysis of the hindgut extracts
      of mated females showed only trace amounts of semiochemicals. A field-trapping
      bioassay in Qinghai, China showed that the four-component "full blend" containing
      the three major components, 2-methyl-3-buten-2-ol, (+/-)-ipsdienol, and (-)-cis
      verbenol, plus a minor component, (-)-trans-verbenol, caught significantly more
      I. nitidus (male/female = 1:2.2) than did the unbaited control and two binary
      blends. The replacement of (+/-)-ipsdienol with nearly enantiomerically pure (-)
      ipsdienol in the "full blend" significantly reduced trap catches, which suggests
      that both enantiomers are needed for attraction. On the other hand, removal of (
      )-trans-verbenol from the active "full blend" had no significant effect on trap
      catches. Our results suggest that the three major components, 2-methyl-3-buten-2
      ol, 74%-(-)-ipsdienol, and (-)-cis-verbenol (at 7:2:1), produced by unpaired fed
      males, are likely the aggregation pheromone components of I. nitidus, thus
      representing the first characterization of an aggregation pheromone system of a
      bark beetle native solely to China.

PMID- 19408046
TI  - Risk factors for massive blood transfusion in cytoreductive surgery: a
      multivariate analysis of 243 procedures.
AB  - BACKGROUND: Cytoreductive surgery (CRS) combined with perioperative
      intraperitoneal chemotherapy (PIC) has demonstrated improved survival in selected
      patients with peritoneal carcinomatosis (PC). This treatment modality is
      associated with high blood loss and often requires massive allogenic red blood
      cell transfusion (MABT). Our study is the first of its kind to evaluate the risk
      factors for intraoperative MABT in peritonectomy procedures. METHODS: Two hundred
      and forty-three consecutive CRS and PIC procedures were evaluated. The
      associations between 17 preoperative and intraoperative risk factors and
      intraoperative MABT (>or=6 units) were assessed by univariate and multivariate
      analysis. RESULTS: One hundred and eighty-six (77%) procedures required
      intraoperative transfusion of packed red blood cells. Ninety-one procedures
      required MABT (37%). Multivariate analysis showed six significant risk factors
      for intraoperative MABT: operative length > 9 h (p < 0.001), preoperative
      hemoglobin < 125 g/l (p < 0.001), operation date prior to 2004 (p = 0.002),
      peritoneal cancer index >or= 16 (p = 0.006), preoperative international
      normalized ratio (INR) >or= 1.2 (p = 0.008), and number of peritonectomy
      procedures >or= 4 (p = 0.021). Statistical analysis also revealed that MABT was
      associated with increased intensive care unit (ICU) (p < 0.001), high-dependency
      unit (HDU) (p = 0.020), and total hospital stay (p < 0.001) and with severe
      morbidity (p < 0.001). CONCLUSIONS: Patients with preoperative anemia, impaired
      coagulation profile or extensive tumor burden are at high risk of MABT.
      Appropriate blood conservation strategies should be adopted in these patients on
      the basis of their risk factors.

PMID- 19408047
TI  - Prognostic significance of phosphorylated FOXO1 expression in soft tissue
      sarcoma.
AB  - BACKGROUND: Forkhead box O1 (FOXO1; forkhead in rhabdomyosarcoma, FKHR) is a key
      transcription factor that regulates the cell cycle and apoptosis, and therefore
      is considered to be involved in cell transformation and tumorigenesis. Expression
      of FOXO1 in soft tissue sarcoma (STS) and its correlation with
      clinicopathological factors and prognostic significance were evaluated. METHODS:
      Expression of phosphorylated FOXO1 (p-FOXO1) in localized STS from 84 adult
      patients, 50 male and 34 female, aged 15-89 (median 54) years, was evaluated by
      immunohistochemistry. Staining intensity of p-FOXO1 in the tumors was judged
      separately for the nucleus and cytoplasm and categorized as follows: level 0,
      absent or faint staining; level 1, weaker than that of endothelial cells in the
      same specimen; and level 2, equal to or stronger than that of endothelial cells.
      RESULTS: Twenty-three (27.3%), 26 (31.0%), and 35 (41.7%), and 32 (38.1%), 30
      (35.7%), and 22 (26.2%) of the tumors showed level 0, 1, and 2 expression of p
      FOXO1 for the nucleus and cytoplasm, respectively. Nuclear p-FOXO1 expression
      correlated with mitotic count, and cytoplasmic p-FOXO1 expression with
      histological subtype, mitotic count, cellularity, myxoid change, Ki-67 labeling
      index, histological grade, American Joint Committee on Cancer stage, and patient
      age. Multivariate analysis revealed nuclear and cytoplasmic p-FOXO1 expression,
      mitotic count, and tumor size to be independent prognostic indicators for overall
      survival, and cytoplasmic p-FOXO1 expression for disease-free survival,
      respectively. CONCLUSIONS: The prognostic significance of p-FOXO1 expression
      level in STS was demonstrated.

PMID- 19408048
TI  - Recall of and reactions to a surgeon referral letter for BRCA genetic counseling
      among high-risk breast cancer patients.
AB  - BACKGROUND: The oncology care setting represents an important opportunity to
      identify and refer women at increased risk for hereditary breast and ovarian
      cancer. However, little is known about the effectiveness of provider approaches
      to inform patients of hereditary cancer risk or patient uptake of genetic
      counseling (GC). This qualitative study examined the impact of a surgeon referral
      letter on recently diagnosed breast cancer patients' uptake of BRCA GC. METHODS:
      Qualitative open-ended, in-depth interviews were conducted with 26 high-risk
      breast cancer patients sent a referral letter for BRCA GC by their surgeon. Data
      were analyzed by a grounded theory approach. RESULTS: Most women (approximately
      80%) recalled receiving the letter, and 62% of all (n = 16) women pursued GC.
      Recall of the letter did not seem to be associated with uptake of GC (P = .49,
      Fisher's exact test). The results highlight key areas for improvement that may
      help increase the impact of the letter. Half of the women in this sample believed
      that the letter was sent to all breast cancer patients, rather than those with
      specific risk factors. Few women mentioned any implications for the information
      obtained during GC or testing regarding their current breast cancer diagnosis or
      treatment. Of the women who did not attend, many perceived that dealing with the
      GC and testing process in the midst of a cancer diagnosis and treatment was
      overwhelming. Among the women who had chosen not to attend GC, most stated they
      would reconsider after completing their treatment. CONCLUSIONS: Patient recall of
      a surgeon referral letter does not seem to increase the number of high-risk women
      who attend GC after a breast cancer diagnosis. The letter approach in its current
      format does not seem to be a wholly effective means of communicating with some
      patients who may be overwhelmed by their cancer diagnosis or unaware that GC and
      testing may have implications for their current treatment decisions, possibly
      resulting in a missed opportunity to engage in informed decision making.

PMID- 19408049
TI  - Safety of gastric resections during cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy for peritoneal carcinomatosis.
AB  - BACKGROUND: Cytoreductive surgery (CRS) including gastric resection combined with
      hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the prognosis of
      selected patients with peritoneal surface malignancies. Perioperative morbidity
      of this aggressive treatment strategy is high; however, overall mortality can be
      low in specialized centers. The aim of this study was to assess the safety of
      gastric resections with anastomosis during CRS and HIPEC. METHODS: Between 2005
      and 2008, 204 patients underwent CRS and HIPEC at our tertiary referral centre.
      Of these, 37 procedures (male/female 24/13, median age 55 years) included gastric
      resections. The clinical data of all patients were introduced into a database and
      analyzed with respect to the morbidity associated with the gastric resections.
      RESULTS: Of all patients included, 16 had pseudomyxoma peritonei, 11 gastric
      carcinoma, 4 ovarian carcinoma, 3 malignant peritoneal mesothelioma, and 3 colon
      carcinoma. Twenty-seven patients had previous surgery (n = 22) and/or systemic
      chemotherapy (n = 18). Fifteen total gastrectomies, 3 subtotal gastrectomies, 12
      distal gastrectomies, and 7 gastric wedge resections were performed during CRS.
      The overall postoperative morbidity was 45%; main surgical complications were
      pancreatitis (n = 6), abdominal abscess (n = 4), bile leakage (n = 2), and
      digestive fistula (leakage of ileorectostomy and small bowel perforation) (n =
      2). However, no complications occurred at the site of the esophageal anastomosis
      (n = 15), gastric anastomosis (n = 15) or gastric suture (n = 7). No patient died
      postoperatively during the hospitalization period. CONCLUSIONS: CRS in
      combination with HIPEC is associated with high postoperative morbidity; however,
      anastomosis following total or subtotal gastrectomy is safe in experienced
      centers. No leakages related to gastric resections occurred in this high-risk
      patient group.

PMID- 19408051
TI  - Effect of age on survival of clinical stage I non-small-cell lung cancer.
AB  - BACKGROUND: Elderly patients with early-stage lung cancer are less likely to
      undergo tumor resection because of concerns about their ability to tolerate
      surgery or perceived limited life expectancy. The objective of this study was to
      evaluate the impact of age and competing risks on outcomes of elderly patients
      with stage I non-small-cell lung cancer (NSCLC). METHODS: We identified 27,859
      cases of histologically confirmed, stage I NSCLC from the Surveillance,
      Epidemiology, and End Results registry. Patients were grouped by age (<60, 61-69,
      70-79, >or=80 years) and surgical resection status. Relative survival rates were
      compared amongst treatment groups by age strata to determine the potential impact
      of surgery and the contribution of competing risks to overall mortality. RESULTS:
      Patients aged <60, 61-69, 70-79, and >or=80 years represented 20%, 32%, 37%, and
      11% of cases. The rate of surgical resections declined from 95% of patients <60
      years, to 79% of patients aged >or=80 years. While 5-year relative survival rates
      were somewhat lower among males >or=80 years compared with those <60 years (63.5%
      versus 69.2%), there were no significant differences in relative survival among
      resected women or unresected patients, regardless of sex. Most deaths in
      unresected patients were attributed to lung cancer across all age groups.
      CONCLUSIONS: Elderly patients who undergo resection achieve relative survival
      rates that are comparable to their younger counterparts. In unresected patients,
      lung cancer is the major source of mortality, even in the oldest age groups,
      suggesting that elderly patients with stage I lung cancer should receive
      aggressive surgical management when possible.

PMID- 19408050
TI  - Dickkopf-1 expression as a marker for predicting clinical outcome in esophageal
      squamous cell carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Dickkopf-1 (DKK1) is the inhibitor of the canonical
      Wnt signaling pathway, however it is highly transactivated in various cancers,
      suggesting the presence of unknown mechanism. Its implication in human esophageal
      squamous cell carcinoma (ESCC) has not been sufficiently investigated. PATIENTS
      AND METHODS: We evaluated DKK1 protein expression in resected specimens from 170
      patients with ESCC by immunohistochemistry. Tumors were categorized as positive
      or negative for DKK1. The relationships between DKK1 expression in ESCC and
      various clinicopathological parameters and prognosis (disease-free survival; DFS)
      were analyzed separately. RESULTS: Immunohistochemically, 72 (42.4%) tumors were
      DKK1 positive while no significant staining was observed in the normal squamous
      epithelium except for few basal cells. There was no significant relationship
      between DKK1 expression in ESCC and any of the clinicopathological parameters
      tested in this study. Patients with DKK1-positive tumors had poorer DFS than
      those with negative ESCC (5-year DFS; 31.5% versus 53.6%, P = 0.0062). Univariate
      analysis showed a significant relationship between pT [hazard ratio (HR) = 2.944,
      95% confidence interval (CI) = 1.713-5.059, P < 0.0001], number of pN (HR =
      2.836, 95% CI = 1.866-4.309, P < 0.0001), lymphatic invasion (HR = 2.892, 95% CI
      = 1.336-6.262, P = 0.0070), and DKK1 expression (HR = 1.763, 95% CI = 1.167
      2.663, P = 0.0071) and DFS. Multivariate analysis including the above four
      parameters identified pT (HR = 2.053, 95% CI = 1.157-3.645, P = 0.0140), pN
      number (HR = 2.107, 95% CI = 1.362-3.260, P = 0.0008), and DKK1 expression (HR =
      1.813, 95% CI = 1.195-2.751, P = 0.0052) as independent and significant
      prognostic factors for DFS. CONCLUSION: Our data suggest the usefulness of DKK1
      as a novel predictor of poor prognosis of patients with ESCC after curative
      resection and also as a therapeutic target for future tailored therapies against
      ESCC.

PMID- 19408052
TI  - Preoperative serum angiopoietin-2 levels correlate with lymph node status in
      patients with early gastric cancer.
AB  - BACKGROUND: Lymph node metastasis is the most important factor to consider when
      deciding on the modality of resection in patients with early gastric cancer. The
      aim of the present study was to assess the relationship between preoperative
      serum angiopoietin-2, a lymphangiogenic growth factor, and lymph node metastasis
      in patients with early gastric cancer. METHODS: A total of 62 preoperative serum
      samples from patients diagnosed with early gastric adenocarcinoma, and 30 serum
      samples from healthy donors were obtained. The serum levels of angiopoietin-2
      (Ang-2) were quantified by immunoassay. Intra- and peritumor lymphatic vessel
      density (I-LVD and P-LVD) were counted after immunohistochemical staining. The
      relationship between the serum Ang-2 levels and other prognostic variables (tumor
      size, histological type, depth of tumor invasion, I-LDV, P-LDV, presence of lymph
      node involvement, and distant metastasis) were then examined by univariate and
      multivariate linear regression analyses. RESULTS: The median serum levels of Ang
      2 in patients were higher than those of healthy controls [311.1 ng/mL,
      interquartile range (IQR) 256.7-311.1 ng/mL versus 286.5 ng/mL, IQR 226.9-286.5
      ng/mL; Mann-Whitney test, P = 0.016]. Eight patients had metastatic lymph nodes;
      the Ang-2 levels from the patients with metastatic lymph nodes were higher than
      from those with negative lymph nodes (297.5 ng/mL, IQR 251.1-385.8 ng/mL versus
      416.0 ng/mL, IQR 337.1-485.5 ng/mL; Mann-Whitney test, P = 0.019). Elevated serum
      Ang-2 levels were associated with positive lymph node involvement and this
      finding was significant on univariate (P = 0.008) and multivariate logistic
      regression analysis (P = 0.011). CONCLUSION: Serum Ang-2 levels were clinically
      useful markers for lymph node metastasis in patients with early gastric cancer.

PMID- 19408053
TI  - Epigenetics in gastric cancer: challenges for clinical implications.

PMID- 19408055
TI  - Importance of early splenectomy in patients with hepatosplenic T-cell lymphoma
      and severe thrombocytopenia.
AB  - OBJECTIVE: T-cell lymphomas (TCLs) classically have a poorer response to therapy
      when compared with B-cell lymphomas and account for only 10-15% of all lymphoid
      malignancies. Hepatosplenic TCLs are a rare subset of this group that usually
      present with hepatosplenomegaly, B-symptoms, and only rarely with
      lymphadenopathy. BACKGROUND: This disease process, also known as gamma/delta
      (gamma/delta) TCL because of the expression of the T-cell receptor gamma/delta
      chain, tends to present in young male patients. Hepatosplenic TCLs have recently
      gained notoriety because of the realization that patients with long-term
      treatment of some immunomodulators can develop this potentially fatal disease.
      These facts are exacerbated by the fact that patients with this disease rarely
      enjoy remissions of more than brief duration with common chemotherapeutic agents
      or bone marrow transplants. A novel agent, pralatrexate, has recently been found
      to have a dramatic activity in this patient population with refractory/relapsed
      disease. Unfortunately, patients with hepatosplenic TCL often present with
      thrombocytopenia and this new agent is contraindicated in these patients because
      of the potential exacerbation of thrombocytopenia with this agent. METHODS:
      Because of this we attempted a laparoscopic-assisted splenectomy in one patient
      with grade 4 thrombocytopenia. RESULTS: Postoperatively the patient's
      thrombocytopenia resolved, permitting him to begin treatment with this
      potentially life-saving agent. CONCLUSION: Due to the lethality of this disease
      and potential efficacy of new therapies, we believe splenectomy should be
      considered in patients with hepatosplenic lymphoma in an effort to improve the
      treatment options and survival of patients with this challenging disease.

PMID- 19408054
TI  - Prophylactic total gastrectomy (PTG) for hereditary diffuse gastric cancer
      (HDGC): the Newfoundland experience with 23 patients.
AB  - BACKGROUND: Hereditary diffuse gastric cancer (HDGC) results from truncating
      mutations of the CDH1 (E-cadherin) gene. It is an autosomal dominant cancer
      susceptibility syndrome with a lifetime risk of diffuse gastric cancer (DGC) of
      60-80%, with a mean age of onset of 37 years. There exists no adequate screening
      test for DGC. Early intramucosal diffuse/signet-ring cell carcinomas have been
      found in prophylactic total gastrectomy (PTG) specimens following normal
      preoperative endoscopy. Total gastrectomy has been advocated on a prophylactic
      basis. The aim of this study was to report our experience with PTG in 23 patients
      from the Canadian province of Newfoundland and Labrador. This is the largest
      series worldwide. METHODS: A retrospective study of consecutive patients
      undergoing PTG for HDGC was performed. All patients were confirmed to have a
      truncating mutation of the CDH1 gene. RESULTS: Twenty-three patients underwent
      PTG between February 2006 and November 2008. Major complications were found in
      4/23 patients (17%), with no mortality. Two of 23 patients (9%) had positive
      mucosal biopsies on preoperative EGD. Twenty-two of 23 patients (96%) had
      evidence of diffuse/signet-ring carcinoma on final standardized pathological
      evaluation. Therefore, 21/23 (91%) were not picked up by preoperative EGD
      screening. CONCLUSIONS: PTG can be performed in patients with HDGC with a low
      rate of serious complications. Methods of reconstruction incorporating a pouch
      reservoir and preservation of the postgastric branches of the vagus nerves need
      to be explored. More refined penetrance estimates, effective screening protocols,
      and long-term psychological and functional outcomes following PTG require
      organized multicenter collaborative efforts.

PMID- 19408056
TI  - Systematic subsegmentectomy by ultrasound-guided finger compression for
      hepatocellular carcinoma in cirrhosis.
AB  - BACKGROUND: Systematic and extensive use of intraoperative ultrasound (IOUS)
      allows us to perform new conservative surgical procedures in liver surgery. This
      video shows systematic subsegmentectomy by IOUS-guided finger compression for a
      case of hepatocellular carcinoma (HCC) in cirrhosis. METHODS: The case of a 69
      year-old woman with a single 3.5-cm HCC in segment 3 is presented. The patient
      has hepatitis C virus (HCV)-related well-compensated cirrhosis. After performing
      a T-inverted laparotomy, the IOUS is carried out for staging. Then, the area of
      resection is anatomically marked by IOUS-guided finger compression of the
      subsegmental portal branch feeding the tumor in segment 3. Thus, the resection is
      performed under intermittent Pringle maneuver using Pean-clasia and bipolar
      forceps. RESULTS: Ninety-day mortality and morbidity for this patient were nil.
      No blood transfusions were required. The patient was discharged 8 days after
      surgery. CONCLUSIONS: Systematic subsegmentectomy by IOUS-guided finger
      compression is a feasible and effective technique, especially for HCC in
      cirrhosis. It may be potentially applied in each segment of liver as long as the
      thickness of the parenchyma and the anatomy of liver are suitable. We believe
      that this technique should be part of the modern liver surgeon's armamentarium.

PMID- 19408057
TI  - Clinicopathological factors and nomograms predicting nonsentinel lymph node
      metastases after neoadjuvant chemotherapy in breast cancer patients.
AB  - BACKGROUND: Studies have demonstrated the feasibility and accuracy of sentinel
      lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) in breast cancer.
      Some SLN-positive patients have low risk of nonsentinel lymph node (non-SLN)
      involvement. Our goal was to determine clinicopathological factors correlating
      with the presence of non-SLN metastases in patients after NAC and to assess the
      validity of nomograms predicting additional axillary metastases. METHODS:
      Patients with infiltrating breast carcinoma (n = 132) were studied prospectively.
      All patients received NAC. At surgery, SLN biopsy followed by axillary lymph node
      dissection was performed. Lymphatic mapping was done using the isotope method.
      Fifty-one patients were SLN positive. RESULTS: In univariate analysis, tumor size
      (P = 0.016) and the size of SLN metastases (P = 0.0055) were significantly
      correlated with the presence of non-SLN metastases. In multivariate analysis, SLN
      macrometastases (P = 0.047) conferred significantly increased risk of non-SLN
      metastases. The Memorial Sloan-Kettering Cancer Center nomogram was not reliably
      predictive for non-SLN metastases (area under the receiver operating
      characteristic curve, AUC, of 0.542), whereas the MD Anderson (AUC 0.716) and
      Tenon scoring systems (AUC 0.778) were validated. CONCLUSION: Our results suggest
      that clinicopathological factors predicting non-SLN involvement in SLN-positive
      patients with and without NAC are essentially the same. The risk of involvement
      may be assessed using existing nomograms, but additional large prospective
      studies are needed to determine their accuracy in patients after NAC.

PMID- 19408059
TI  - Comparative effectiveness research: medical practice, payments, and politics: the
      need to retain standards of medical research.

PMID- 19408058
TI  - Primary care physicians treat somatization.
AB  - BACKGROUND: We hypothesized that somatizing patients managed by primary care
      physicians (PCP) would improve with a relationship-based intervention. METHODS:
      We randomized 30 adults with medically unexplained symptoms to treatment or usual
      care. Four PCPs were trained to intervene with cognitive-behavioral,
      pharmacological, and patient-centered management and deployed the intervention
      with seven scheduled visits over 12 months. Outcomes obtained at baseline and 12
      months were: Mental component summary (MCS), the primary endpoint, and measures
      of physical and psychological symptoms and of satisfaction with the PCP. RESULTS:
      Patients averaged 52.5 years; 83.3% were female; 79.6% were black. Using a
      difference of differences approach, we found that the intervention produced a
      large effect size (ES) (0.82; CI: 0.08 to 1.57) for the MCS in the predicted
      direction, similar to the ES for physical (-0.80; CI: -1.55 to -0.04) and
      psychological (-1.06; CI: -1.83 to -0.28) improvement and for increased
      satisfaction with the PCP (0.94; CI: 0.15 to 1.74). Using ANCOVA in a sensitivity
      analysis, we found that the ES fell slightly (0.59), while other measures were
      unchanged. CONCLUSIONS: Moderate-large effect sizes support the hypothesis that
      PCPs can effectively treat somatization. This points to the importance of
      performing a full RCT.

PMID- 19408060
TI  - 50 years ago in CORR: function fixation of femoral neck fractures; telescoping
      nail technic. William K. Massie MD. CORR 1958;12:230-255.

PMID- 19408061
TI  - Periprosthetic infection due to resistant staphylococci: serious problems on the
      horizon.
AB  - Prosthetic joint infections (PJI) caused by methicillin-resistant staphylococci
      represent a major therapeutic challenge. We examined the effectiveness of
      surgical treatment in treating infection of total hip or knee arthroplasty caused
      by methicillin-resistant staphylococcal strains and the variables influencing
      treatment success. One hundred and twenty-seven patients were treated at our
      institution between 1999 and 2006. There were 58 men and 69 women, with an
      average age of 66 years. Patients were followed for a minimum of 2 years or until
      recurrence of infection. Debridement and retention of the prosthesis was
      performed in 35 patients and resection arthroplasty in 92. Debridement controlled
      the infection in only 37% of cases whereas two-stage exchange arthroplasty
      controlled the infection in 75% of hips and 60% of knees. Preexisting cardiac
      disease was associated with a higher likelihood of failure to control infection
      in all treatment groups. Antibiotic-resistant Staphylococci continue to
      compromise treatment outcome of prosthetic joint infections, especially in
      patients with medical comorbidities. New preventive and therapeutic strategies
      are needed. LEVEL OF EVIDENCE: Level IV, therapeutic study.

PMID- 19408062
TI  - Protrusio acetabuli: new insights and experience with joint preservation.
AB  - Protrusio acetabuli is identified on anteroposterior (AP) radiographs of the
      pelvis with an acetabular line projecting medial to the ilioischial line. We
      documented this radiographic sign and additional radiographic parameters in 19
      patients (29 hips) with protrusio and compared the parameters to those of 29
      older patients (29 hips) with advanced primary osteoarthritis (OA) but no
      protrusio and 12 younger patients (22 hips) with protrusio but no advanced OA. A
      negative acetabular roof angle and particularly large acetabular fossa were more
      apparent in younger patients; these hips suggest the destruction of a protrusio
      hip begins less in the medial joint area and more in the posteroinferior joint,
      and the mechanism is driven less by excessive medially directed forces but by a
      pincer impingement. While the indication for joint-preserving surgery currently
      consists primarily of a valgus femoral osteotomy based on AP radiographs and
      patient age, modern decision making also relies on cartilage evaluation and
      requires advanced surgical techniques. We conclude joint-preservation surgery
      must be tailored to the individual hip morphology.

PMID- 19408063
TI  - Fenestration of the double origin of the posterior inferior cerebellar artery
      associated with a contralateral vertebral artery dissection.
AB  - Double origin of the posterior inferior cerebellar artery (PICA) is an infrequent
      developmental anomaly predisposing an individual to intracranial aneurysm
      formation. Fenestration of the PICA is extremely rare, and furthermore,
      fenestration of the double origin of the PICA in association with an intracranial
      aneurysm is unique. We present the first reported case of fenestration of the
      double origin of the PICA associated with a dissecting aneurysm of the
      contralateral vertebral artery (VA) that healed spontaneously after medical
      observation.

PMID- 19408064
TI  - MRI detection of the cerebellar syndrome in Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob Disease (CJD) is characterized by bilateral basal ganglia
      hyperintensities on T2W and diffusion-weighted imaging (DWI) magnetic resonance
      imaging (MRI) scans, consistent with its extrapyramidal neurological
      manifestations. MRI is diagnostically uninformative about the cerebellar
      symptoms, equally prominent in CJD. This study was undertaken to explain this
      apparent paradox. Eleven CJD patients with definite cerebellar or brain stem
      symptoms were selected from a large prospective study, as well as 11 healthy
      controls matched for age and gender. All subjects participated in a standardized
      MRI protocol, including SPGR, fluid-attenuated inversion recovery (FLAIR), DWI
      and diffusion tensor imaging (DTI). All subjects underwent detailed examination
      by a neurologist blinded to the radiological findings, who predicted the expected
      site of cerebral abnormalities. MRI showed good sensitivity for the abnormalities
      predicted in the cortex (80-90%) and basal ganglia (100%). None of the standard
      MRI sequences, including DWI, DTI, and FLAIR, revealed any tissue abnormalities
      in cerebellum or brain stem. Apparent diffusion coefficient (ADC) values,
      however, were substantially and significantly elevated in several cerebellar
      structures, where also the volumetric (VBM) analysis revealed elevated
      cerebrospinal fluid volume, suggesting focal cerebellar atrophy in these CJD
      patients. In patients with CJD, DWI appears sensitive to the reduced diffusivity
      in cortex and basal ganglia but insensitive to cerebellar involvement. We propose
      that the radiological hallmark of cerebellar pathology in CJD is atrophy,
      revealed quantitatively by both VBM and elevated diffusivity, which is
      identifiable on ADC maps but poorly visualized in nonquantitative DWI images.

PMID- 19408067
TI  - Use of a modified ProSeal laryngeal mask airway to facilitate diagnostic
      fiberoptic bronchoscopy in anesthetized patients.

PMID- 19408065
TI  - Assessment of myocardial perfusion with Tc-99m: image is everything.

PMID- 19408066
TI  - Elevated activated partial thromboplastin time does not correlate with heparin
      rebound following cardiac surgery.
AB  - PURPOSE: Exposure to cardiopulmonary bypass (CPB) is associated with
      postoperative coagulopathy and hemorrhage. Recent literature indicates that
      heparin rebound occurs almost universally following cardiac surgery. We conducted
      this pilot study to evaluate if the presence of residual circulating heparin
      following cardiac surgery can be diagnosed by elevation of activated partial
      thromboplastin time (APTT). METHOD: After obtaining Research Ethics Board
      approval, blood samples from 30 patients receiving heparin for CPB were evaluated
      at the time of intensive care unit admission and 2, 4, and 6 hr thereafter.
      Activated clotting time, whole blood heparin concentration (Hepcon HMS Plus,
      Medtronic), anti-Xa levels, and APTT were measured at each time point. Samples
      with prolonged APTT were subjected to mechanistic studies with heparin adsorption
      and 1:1 mixing. RESULTS: Anti-Xa was elevated in 52 of the 120 blood samples
      (0.08 +/- 0.08 U . mL(-1), mean +/- SD). APTT was elevated in 49 (40.8%) samples
      with an average of 51.4 +/- 31.9 sec. At all time points, the APTT correlated
      poorly with anti-Xa levels with correlation coefficients ranging from -0.26 to 
      0.05. Mean APTT was modestly, but not significantly, associated with total dose
      of protamine with r = 0.34 (CI: -0.03, 0.62). After 1:1 mixing studies, APTT
      returned to normal in most (82%) samples tested. CONCLUSION: Circulating residual
      heparin is commonly presented following cardiac surgery and does not correlate
      with APTT. Considering that mixing studies normalize APTT in most samples,
      elevated APTT following CPB may reflect deficiency of coagulation factors or
      presence of a coagulation inhibitor such as protamine. Further studies are
      required to confirm this observation.

PMID- 19408068
TI  - Berlin declaration on the Quality of Life for Older Adults: closing the gap
      between scientific knowledge and intervention.

PMID- 19408071
TI  - Possible treatment strategies for triple-negative breast cancer on the basis of
      molecular characteristics.
AB  - The intrinsic subtype has demonstrated that breast cancers can be classified into
      biologically and clinically meaningful subgroups. Most breast tumors categorized
      as one of the intrinsic subtypes, i.e., basal-like, have an estrogen receptor
      negative, progesterone receptor-negative, and human epidermal growth factor
      receptor 2-negative phenotype, so-called triple-negative (TN) phenotype; however,
      TN breast cancer is not a synonym for basal-like subtype. TN breast cancers
      account for 10-20% of all breast cancers, and are more biologically aggressive
      than breast cancers of other subgroups. Tailored therapies, such as endocrine
      therapy and anti-HER2 therapy, are not applicable to TN breast cancer. To develop
      novel strategies against TN breast cancer, it is essential to understand the
      specific pathways driving the aggressive behavior of TN breast cancer.
      Preclinical and clinical studies have suggested that DNA-damaging agents and poly
      ADP-ribose polymerase inhibitors are active in TN breast cancer harboring BRCA1
      dysfunction; anti-epidermal growth factor receptor (EGFR) antibodies and EGFR
      tyrosine kinase inhibitors are active in TN breast cancer with EGFR gene
      amplification; dasatinib is active in TN breast cancer with activated Src
      tyrosine kinases; inhibitors of a mammalian target of rapamycin are active in TN
      breast cancer with loss of PTEN tumor suppressor; antiangiogenic therapies
      enhance antitumor activity of chemotherapeutic agents in hypervascular TN breast
      cancer; and irinotecan, trabectedin, ixabepilone, and ABI-007 are active in TN
      breast cancer. A number of clinical trials are ongoing to clarify the antitumor
      activity of these challenging treatment strategies. Further biological
      characterization of TN breast cancer is needed to develop more specific treatment
      strategies against TN breast cancer.

PMID- 19408072
TI  - Toward 300 liver transplants a year.
AB  - The technical success of cadaveric whole-size liver transplantation and better
      immunosuppressive drugs has extended the application of this life-saving
      procedure to include patients with irreversible acute and chronic liver diseases.
      However, because of the scarcity of cadaveric liver grafts, living-donor liver
      transplantation (LDLT) has emerged as an alternative to cadaveric-donor liver
      transplantation (CDLT), especially in Asia. In Korea, 8% of the population are
      hepatitis B virus (HBV) carriers, and the resultant HBV cirrhosis, with or
      without hepatocellular carcinoma (HCC), is common in the 40- to 60-year-old
      generation. Accordingly, many patients require orthotopic liver transplantation
      (OLT). In 1992, we started performing CDLTs in the Asan Medical Center. In 1994,
      the first successful pediatric LDLT was performed in Korea, on a 9-monthold
      infant with biliary atresia. In 1997, the first successful adult LDLT was
      performed in our department, using a left lobe, on a 37-year-old patient with HBV
      cirrhosis associated with HCC. Even after the first successful right-lobe LDLT,
      we faced the obstacle of anterior segment congestion of a right-lobe graft, and
      initiated reconstruction of the middle hepatic venous tributaries of a right-lobe
      graft in 1998. In 1999, we performed more than 100 OLTs a year. Insufficient
      graft size has hindered the expansion of adult LDLT, when the remaining left-lobe
      of potential donors is too small to assure donor safety. Dual two-left-lobe graft
      LDLT (transplanting from two donors into one recipient) was developed in 2000 to
      solve graft-size insufficiency and minimize donor risk. More than 200 OLTs a year
      have been performed since 2004, while broadening the indications for adult LDLT
      to near complete obstruction of the portal vein, with the application of
      intraoperative portography (IOP) and portal vein stenting. In 2007, 320 LTs were
      performed, including 276 adult LDLTs, 10 pediatric LDLTs, and 34 CDLTs (including
      7 adult and 1 pediatric split-liver transplant). There has been no donor
      mortality in LDLT. With technical refinement and advanced perioperative care, the
      in-hospital mortality of recipients has dropped to 4%: attributed to the
      dedication of our liver transplantation team members.

PMID- 19408073
TI  - Advantage of sentinel lymph node biopsy before neoadjuvant chemotherapy in breast
      cancer treatment.
AB  - Lymph node status is a key factor in determining the stage of breast cancer and
      the most appropriate therapy and for predicting the outcome of patients. Accurate
      identification of sentinel lymph nodes (SLNs) preoperatively is of clinical
      importance. Sentinel lymph node biopsy (SLNB) causes less lymph edema of the
      upper arm than axillary lymph node dissection (ALND) with a high accuracy rate
      and low false-negative rate (FNR). Neoadjuvant chemotherapy (NAC) can be given
      not only to patients with locally advanced breast cancer, but also to those with
      axillary lymph node metastasis and an operable tumor. However, SLNB after NAC
      results in a lower identification rate and a higher FNR than SLNB before
      treatment. Recently, a hybrid imaging device has been developed, which consists
      of single photon emission computed tomography (CT, SPECT) and a low-dose CT
      installed on the same platform. This imaging system offers an easy and safe
      method of performing SLNB under local anesthesia. To identify the initial cancer
      stage in patients who will be treated by systemic therapy before surgery, SLNB
      should be performed prior to systemic treatments, using a well-developed
      navigating tool, such as SPECT/CT.

PMID- 19408074
TI  - Use of levosimendan in patients with ischemic heart disease following mechanical
      reperfusion.
AB  - Cardiac failure is among the most significant conditions associated with acute
      coronary syndrome. In ischemic heart disease, serious hemodynamic problems are
      reported in patients with left ventricular dysfunction during the acute phase
      despite mechanical revascularization. Several positive inotropic agents in
      addition to intra-aortic balloon pump (IABP) are required to support patients
      with impaired left ventricular pump function during this phase. Intravenous
      inotropic agents, beta-mimetics, and phosphodiesterase inhibitors lead to
      increases in the incidence of arrhythmia and myocardial O(2) consumption owing to
      their effect of increasing intracellular calcium amount, although they produce
      rapid hemodynamic improvements in cardiac failure. This causes severe problems
      particularly in cardiac failure of ischemic origin. Recently, levosimendan, a
      calcium-sensitizing agent with cardioprotective properties, is being used alone
      or in combination with IABP in cases with severe left ventricular systolic
      dysfunction during mechanical revascularization procedures (percutaneous coronary
      interventions, coronary bypass surgery). This review includes studies with
      levosimendan in cases not recovering due to myocardial stunning in the acute
      phase despite mechanical approaches applied.

PMID- 19408075
TI  - Fantoni translaryngeal tracheostomy versus ciaglia blue rhino percutaneous
      tracheostomy: a retrospective comparison.
AB  - PURPOSE: To compare the operative technique and complications of the Fantoni
      tracheostomy (TLT) with those of the Ciaglia Blue Rhino tracheostomy (CBR). We
      also compared the costs of mini-invasive tracheostomy with those of surgical
      tracheostomy (ST). METHODS: Between January 1998 and January 2006, 530 patients
      needed emergency intubation and protracted assisted ventilation in our
      department. We performed 470 mini-invasive tracheostomies: as TLT in 350 and as
      CBR in 120. The time between intubation and tracheostomy was 4 +/- 1 days.
      Interventions were carried out in our intensive care unit (ICU). RESULTS: One
      hundred and nine patients died within 20 +/- 5 days of intervention, but 361 are
      still alive after 100 +/- 3 months. TLT and CBR complications were independent of
      the operative technique (P = 0.74, r = 0.285 vs P = 0.61, r = 0.271) or procedure
      time (P = 0.95, r = 0.297 vs P = 0.92, r = 0.295). Ciaglia Blue Rhino
      tracheostomy was noted to have a cost-benefit advantage over TLT and ST (P =
      0.0002, P = 0.009, P = 0.22, respectively). The average time until decannulation
      was 20 +/- 1 days. CONCLUSIONS: Mini-invasive tracheostomies are easy, safe, and
      fast. Ciaglia Blue Rhino tracheostomy took less time to perform and had fewer
      complications than TLT, because the technique was simpler.

PMID- 19408076
TI  - Surgical management of colorectal cancer in patients with psychiatric disorders.
AB  - PURPOSE: We analyzed the surgical data and evaluated the management of colorectal
      cancer (CRC) in patients with psychiatric disorders. METHODS: We reviewed the
      medical records of 83 patients who underwent elective surgery for CRC and divided
      them into a psychiatric disorder group and a control group to compare the
      operative data and available clinical information. RESULTS: Of the 83 patients,
      27 had psychiatric disorders. The most characteristic symptom of CRC was bloody
      stool in the psychiatric disorder group, and occult blood in the control group.
      Postoperative pneumonia occurred significantly more often in the psychiatric
      group (14.8% vs 1.8%, P = 0.019). Patients with a psychiatric disorder needed
      significantly more psychotropic drugs (70.4% vs 7.1%, P < 0.001), more physical
      restraint (44.4% vs 12.5%, P = 0.001), and exhibited more resistant behavior
      (51.9% vs 8.9%, P < 0.001) postoperatively than the controls. Moreover, a
      significant decrease in serum albumin (Alb) and total protein (TP) was seen in
      the psychiatric disorder group on postoperative days (PODs) 21 and 28. A
      psychiatric disorder was a significant predictive factor for a decrease in TP
      (odds ratio [OR] 24.2) and Alb (OR 8.6). CONCLUSIONS: Insufficient nutrition in
      the psychiatric disorder group was not attributable solely to the higher
      incidence of postoperative complications. As psychiatric disorders compromise
      nutrition, integral treatment provided by surgeons and psychiatrists would
      improve the nutritional status of these patients and reduce the incidence of
      postoperative morbidity.

PMID- 19408077
TI  - Inhibition of lung permeability changes after burn and smoke inhalation by an
      anti-interleukin-8 antibody in sheep.
AB  - PURPOSE: To evaluate the effects of a monoclonal antibody against interleukin-8
      (K2.2) on the microvascular fluid flux after combined injury by burn and smoke
      inhalation. METHODS: Fourteen sheep were prepared surgically by placing a lung
      lymph catheter and a flank lymph catheter to examine the microvascular fluid
      flux. After a recovery period, they were subjected to a combined injury of 40%
      third-degree burns on the flank and smoke inhalation. RESULTS: This combined
      injury induced a rapid increase in burned tissue lymph flow (b-Q(L)) and a
      delayed-onset increase in lung lymph flow (l-Q(L)). The initial increase in b
      Q(L) was associated with an elevation of the lymph-to-plasma oncotic pressure
      ratio, which led to a predominant increase in the burned tissue permeability
      index (b-PI). Pretreatment with K2.2 had no effect on the permeability change
      seen in the burned tissue; however, the lung permeability changes were attenuated
      by pretreatment with K2.2. CONCLUSION: These findings indicate that the
      pathogenesis of the increase in microvascular fluid flux seen after the combined
      injury differs in burned tissue and the lung.

PMID- 19408078
TI  - Tempol reduces bacterial translocation after ischemia/reperfusion injury in a rat
      model of superior mesenteric artery occlusion.
AB  - PURPOSE: We investigated whether Tempol, a water-soluble antioxidant, prevents
      the harmful effects of superior mesenteric ischemia/reperfusion on intestinal
      tissues in rats. METHODS: The rats were divided into three groups of 10. In group
      1, the superior mesenteric artery (SMA) was isolated but not occluded, and in
      groups 2 and 3 the superior mesenteric artery was occluded for 60 min. After
      that, the clamp was removed and reperfusion began. In group 3, 5 min before the
      start of reperfusion, a bolus dose of 30 mg/kg Tempol was administered
      intravenously and continued at a dose of 30 mg/kg for 60 min. All animals were
      euthanized after 24 h and tissue samples were collected for analysis. RESULTS:
      There was a significant increase in myeloperoxidase activity, malondialdehyde
      levels, and the incidence of bacterial translocation in group 2, with a decrease
      in glutathione levels. These parameters were found to be normalized in group 3.
      The intestinal mucosal injury score in group 2 was significantly higher than
      those in groups 1 and 3. CONCLUSION: Tempol prevents bacterial translocation
      while precluding the harmful effects of ischemia/reperfusion injury on intestinal
      tissues in a rat model of superior mesenteric artery occlusion.

PMID- 19408080
TI  - Primary stent placement for late complete occlusion after aortoiliac
      reconstructive surgery: report of a case.
AB  - We report a case that was successfully treated by primary stent placement without
      thrombolysis or thrombectomy for graft thrombosis after aortoiliac reconstructive
      surgery. A 79-year-old man presented with a 2-month history of severe
      intermittent claudication of the right leg. He had undergone a surgical repair of
      abdominal aortic aneurysm with a bifurcated polyester graft 3 years before
      presentation. Digital subtraction angiography revealed total occlusion of the
      right limb of the graft. He underwent primary stent placement on the lesion, and
      completion angiography showed revascularization of the right limb. Primary stent
      placement can be performed to decrease the risks of surgery and increase the
      salvage of a graft with chronic total occlusion.

PMID- 19408081
TI  - Intraoperative indocyanine green fluorescence lymphography, a novel imaging
      technique to detect a chyle fistula after an esophagectomy: report of a case.
AB  - Intraoperative indocyanine green (ICG) lymphography was performed on a 62-year
      old man, who was diagnosed to have chylothorax after an esophagectomy for
      esophageal cancer. After exploration of the thorax, a slowly increasing effusion
      was identified in the mediastinal space above the diaphragm, but the exact site
      of the lymph fistula could not be identified. By injecting 1.5 ml of ICG
      subcutaneously at the bilateral inguinal region, fluorescence images of the lymph
      flow in the thoracic cavity were obtained using a near-infrared camera system.
      The detected leakage point was sutured and the chyle ooze stopped. The
      postoperative course was uneventful. The patient was discharged on the 16th
      postoperative day. This is the first report using ICG fluorescence lymphography
      for the successful intraoperative detection of the exact site of a fistula
      causing chylothorax.

PMID- 19408082
TI  - Adenoendocrine carcinoma of the accessory papilla of the duodenum: report of a
      case.
AB  - This report describes a very rare case of an adenoendocrine carcinoma of the
      accessory papilla of the duodenum. A 70-year-old woman was admitted to the
      hospital complaining of epigastralgia. Gastrointestinal endoscopy showed a
      protruding tumor with ulceration at the accessory papilla of the duodenum. A
      biopsy revealed a small-cell carcinoma. Computed tomography showed a highly
      enhanced tumor in the early phase. No metastatic lesions were shown. Magnetic
      resonance cholangiopancreatography showed dilatation of the pancreatic duct, but
      a normal common bile duct. A pyloruspreserving pancreaticoduodenectomy was
      performed with lymph node dissection. Microscopically, the tumor was a small-cell
      neuroendocrine carcinoma with adenomatous differentiation. An immunohistochemical
      analysis showed positive staining for synaptophysin, chromogranin A, CD56, and
      carbohydrate antigen 19-9. The final diagnosis was an adenoendocrine carcinoma
      with lymph node metastasis. The postoperative course was uneventful and the
      patient is now doing well as an outpatient after 14 months of follow-up.

PMID- 19408079
TI  - Abdominal lymphangioma in children: report of three cases.
AB  - Most cases of abdominal lymphangioma are asymptomatic. However, patients may
      occasionally present with acute abdomen because of an intestinal obstruction or
      peritonitis caused by infected cysts, hemorrhaging, and/or torsion. These
      conditions may differ based on the location of the lymphangioma and do not always
      require emergency surgery. This report presents two cases of abdominal
      lymphangioma derived from the omentum, which required emergency surgery because
      of severe abdominal distension and peritonitis caused by torsion, respectively.
      In contrast, another case of retroperitoneal lymphangioma presented with acute
      abdomen and underwent elective surgery after conservative therapy for
      peritonitis. Elective surgery is acceptable if the symptoms are controllable
      under conservative therapy. However, it is important not to overlook the possible
      lethal complications such as intestinal and/or urological obstruction, aggressive
      peritonitis, and torsion of the cyst, which require emergency surgery.

PMID- 19408083
TI  - Twenty-two metachronous multiple signet-ring cell carcinomas treated with
      repeated gastrectomies and repeated endoscopic mucosal resections: report of a
      case.
AB  - A 45-year-old Japanese woman underwent an endoscopic mucosal resection (EMR) for
      early gastric cancer at the Cancer Institute Hospital in July 1996. The patient
      then underwent a distal gastrectomy in 2002 because of a new early gastric cancer
      and repeated EMR for a total of six early gastric cancers in 2007. Finally, a
      total gastrectomy was performed in February 2008. The pathological examination of
      the resected specimen indicated 14 synchronous multiple early gastric cancers.
      Although the incidence of multiple gastric cancers has been reported to range
      from 5% to 15%, there is usually only a double or triple lesion. Moreover,
      multiple gastric cancer is typically observed in male elderly patients as
      differentiated adenocarcinomas. The present case was a young female patient and
      all of the lesions were intramucosal signet-ring cell adenocarcinomas. The
      carcinogenetic mechanism in this case may therefore be different from that in
      typical multiple gastric cancers. A thorough preoperative examination and regular
      postoperative follow-up are therefore essential for detecting multiple gastric
      cancers in their early stages.

PMID- 19408084
TI  - Laparoscopy-assisted combined resection for synchronous gastric and colorectal
      cancer: report of three cases.
AB  - In gastric cancer patients, the most common form of synchronous cancer is
      colorectal cancer. To reduce the invasiveness of the resection, a laparoscopy
      assisted combined resection was performed in three patients with synchronous
      gastric and colorectal cancer. Although all gastric lesions were in the early
      stages, two colorectal lesions were advanced cases. In all cases, the
      laparoscopic gastric resection and reconstruction was performed first, followed
      by the colorectal resection. In the case of right-side colon cancer in addition
      to gastric cancer, it was relatively easy to perform the combined resection with
      lymph node dissection sharing the same ports used for the gastrectomy, although
      we needed an additional port. In one case, in which rectal cancer was present in
      addition to gastric cancer located in the upper portion of the stomach, a totally
      laparoscopic proximal gastrectomy was combined with a laparoscopy-assisted low
      anterior resection, leaving only a lower abdominal minilaparotomy wound. All
      patients quickly returned to normal activity without remarkable complications,
      with the exception of a wound infection in one patient. With a mean follow-up of
      30.7 months, all patients survived without any sign of recurrence. This procedure
      represents a feasible option for minimally invasive treatment of synchronous
      gastric and colorectal cancer.

PMID- 19408085
TI  - Did ileal knotting trigger labor or did labor cause ileal knotting? Report of a
      case.
AB  - Ileal knotting is a rare but serious complication of pregnancy, with relatively
      high maternal and fetal mortality. We report a case of ileal knotting with
      complications in a pregnant woman without any history of abdominal or pelvic
      surgery. To our knowledge, there is no other report in the international
      literature. Thus, the possibility of ileal knotting should be borne in mind when
      investigating epigastric pain in a pregnant woman without any history of
      abdominal or pelvic surgery, even after the onset of labor pains. Delayed
      surgical intervention can result in maternal and fetal mortality.

PMID- 19408086
TI  - Heterotopic gastric mucosa leading to recurrent intussusceptions: report of a
      case.
AB  - Although most cases of intussusception during childhood are caused by viral
      enlargement of the Peyer's patches, the remainder of the cases may be due to
      congenital anomalies, such as heterotopic gastric mucosa (HGM). This report
      presents a case of HGM in a 4-year-old boy. The patient presented with acute
      abdominal signs with a right lower quadrant mass. His medical history indicated
      three episodes of recurrent intussusceptions. The abdominal ultrasound
      examination detected an intussusception. A laparotomy revealed an ileocolic
      intussusception and reduction was accomplished. During exploration, an
      intraluminal mass in the ileum, which was the lead point, was discovered by
      palpation. An enterotomy showed a 2-cm-diameter crater-shaped mucosal thickening.
      An ileal resection and anastomosis was performed. The histopathological
      examination revealed HGM. Heterotopic gastric mucosa is supposed to be of
      vitellointestinal tract origin and may cause intussusception as being a lead
      point in the ileum. Despite its rarity, HGM should be considered in cases of
      recurrent intussusceptions and diagnostic studies should be performed. A
      laparotomy is required for the diagnosis and treatment in complicated cases.
      Surgical management should include reduction of the intussusception and careful
      manual examination of the ileum which may expose such pathology. An intestinal
      resection and anastomosis is sufficient to prevent complications.

PMID- 19408087
TI  - Primary extranodal non-Hodgkin's lymphoma of the common bile duct manifesting as
      obstructive jaundice: report of a case.
AB  - Primary non-Hodgkin's lymphoma (NHL) of the common bile duct (CBD) manifesting as
      obstructive jaundice is extremely rare: to our knowledge, only 22 cases of
      primary NHL arising from the CBD have been reported. The patient in this case
      report was a 63-year-old man who presented with obstructive jaundice. Abdominal
      sonography, positron emission tomography, and computed tomography showed a mass
      with abnormal 18-fluorodeoxyglucose uptake in pancreatic head. Magnetic resonance
      cholangiopancreatography demonstrated a strictured segment of the CBD with
      proximal bile duct dilatation. We performed pancreaticoduodenectomy for a
      presumptive diagnosis of pancreatic head carcinoma or cholangiocarcinoma of the
      CBD. However, the histological diagnosis was a primary, diffuse, large B-cell
      lymphoma of the CBD. He received three courses of combination chemotherapy,
      including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
      (R-CHOP). The patient remains well, without evidence of tumor recurrence, 8
      months after surgery. In summary, primary NHL of the CBD, despite its rarity,
      should be considered in the differential diagnosis of obstructive jaundice. An
      accurate histopathologic diagnosis and complete surgical resection, followed by
      combination chemotherapy plus rituximab may be effective.

PMID- 19408088
TI  - Superextended hepatectomy for resection of multiple giant hemangiomas: report of
      a case.
AB  - Most liver hemangiomas are small, asymptomatic, and require no treatment.
      Symptoms such as right upper quadrant abdominal pain and fullness are associated
      only with liver hemangiomas larger than 4 cm in diameter. Serious complications
      such as jaundice, Kasabach-Merritt syndrome, and rupture are rare. Surgical
      resection is the only effective treatment, but it is advocated only for patients
      with incapacitating symptoms or complications. We report a case of successful
      superextended hepatectomy with resection of segments III-VIII for multiple,
      bilobar hemangiomas. A 45-year-old woman, who had undergone transcatheter
      arterial embolization (TAE) for inoperable multiple giant liver hemangiomas 4
      years earlier, was referred to our hospital for investigation of abdominal
      distension and consumption coagulopathy. Because of her severe and progressive
      symptoms despite treatment, the other hospital had considered her as a candidate
      for liver transplantation, which she had refused. After careful preoperative
      assessment of the future liver remnant volume and function, we considered that
      resection was possible. Based on our review of large surgical series in the
      literature from 1970, this is the first report of a superextended hepatectomy for
      a benign liver tumor.

PMID- 19408089
TI  - An easy-to-use tool for dressing finger injuries painlessly.
AB  - Finger injuries are among the most common injuries treated in the emergency
      department. After surgical management, surgeons find that patients with finger
      injuries will sometimes experience severe tenderness when dressings are being
      changed. To reduce patients' discomfort an easy-to-use tool for painless finger
      wound dressing has been developed.

PMID- 19408090
TI  - Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma.
AB  - The incidence of hemorrhagic onset in pilocytic astrocytoma and pilomyxoid
      astrocytoma, and the clinical and histological characteristics, were compared to
      other types of neuroepithelial tumors or nonhemorrhagic pilocytic astrocytoma by
      retrospective review of 445 consecutive neuroepithelial tumors treated at our
      institute. Hemorrhagic onset was observed in 4 of 35 (11.4%) patients with
      pilocytic astrocytoma and pilomyxoid astrocytoma, with higher incidence than in
      glioblastoma (3.9%), anaplastic oligodendroglioma (7.7%), and anaplastic
      ependymoma (7.1%). The hemorrhagic onset occurred in 2 patients with sporadic
      pilocytic astrocytoma, 1 with pilocytic astrocytoma associated with
      neurofibromatosis type 1, and 1 with pilomyxoid astrocytoma. There was no
      correlation between hemorrhagic onset and clinical features, including age, sex,
      tumor location, proliferative activity, or microvascular proliferation.
      Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma is not as
      uncommon as was previously thought, so pilocytic astrocytoma or pilomyxoid
      astrocytoma should be considered in the differential diagnosis of patients with
      brain tumors manifesting as hemorrhagic onset.

PMID- 19408091
TI  - Tanycytic ependymoma of the spinal cord with anaplastic cytological features.
AB  - In a 43-year-old man, an intramedullary spinal cord tumor spreading from the
      level of the T2 to T5 vertebrae was subtotally resected. The tumor predominantly
      consisted of a fascicular proliferation of spindle cells having bland nuclei and
      bipolar, long cytoplasmic processes, and a few perivascular pseudo-rosettes were
      found. Although there were no true ependymal rosettes, intracytoplasmic dot-like
      immunoreactivity for epithelial membrane antigen (EMA) was found in a few cells.
      In some areas, a dense and diffuse proliferation of anaplastic, short-spindled
      cells having hyperchromatic nuclei and scant cytoplasm was noted, and the Ki-67
      labeling index was remarkably higher (18.2%) in these areas. Neither
      microvascular proliferation nor necrosis was observed. In the boundary region,
      these two areas showed gradual transition from one to the other. The patient has
      remained free from recurrence for 10 months postoperatively. This is the first
      documentation of tanycytic ependymoma in which tumor cells showed anaplastic
      cytological features.

PMID- 19408092
TI  - A case of an anaplastic ependymoma with gliosarcomatous components.
AB  - A 29-year-old woman presented with a severe headache. Computed tomography
      revealed a large cystic lesion with a mural nodule-like mass homogeneously
      enhanced with contrast medium in the right cerebellum. The tumor was removed, and
      pathological studies revealed a cerebellar astrocytoma corresponding to World
      Health Organization grade II. When she was 35 years old, or 6 years after the
      surgery, magnetic resonance imaging revealed a recurrence of the tumor in the
      right cerebellum, and subtotal removal of the recurrent tumor was performed.
      Pathological studies revealed a mixed glioblastoma multiforme and anaplastic
      ependymoma. Chemotherapy (Paraplatin and VePeside-S) and focal radiation therapy
      at 60 Gy were administered following surgery. Thereafter, at 39 years of age, or
      4 years after radiation therapy, magnetic resonance imaging again revealed a
      recurrence of the tumor, which was heterogeneously enhanced with
      gadoliniumdiethylenetriamine pentaacetic acid in the right cerebellum. Subtotal
      removal of the tumor was performed; pathological studies revealed an anaplastic
      ependymoma with sarcomatous components. Immunohistochemical findings showed some
      parts of the sarcomatous components to stain positively for glial fibrillary
      acidic protein and, as a result, these sarcomatous components were diagnosed to
      be gliosarcoma.

PMID- 19408093
TI  - A rare astrocytic tumor with rhabdoid features.
AB  - We report an extremely rare tumor presenting with rhabdoid features in the left
      temporoparietal lobe near the trigone in an 18-year-old Japanese man. This tumor
      mainly consisted of medium to large round cells that proliferated diffusely and
      incoherently with a scant extracellular matrix. These tumor cells had an
      eccentric nucleus and an eosinophilic cytoplasm containing inclusion bodies and
      bundles of intermediate filaments. The nuclei of these cells were vesicular with
      prominent nucleoli. This tumor had an area appearing to be diffuse astrocytoma
      peripherally and lacked a primitive neuroectodermal tumor component, a
      mesenchymal component, and epithelial differentiation. INI expression, which is
      not observed in atypical teratoid/ rhabdoid tumor (AT/RT), was found in this
      tumor. From these findings, we concluded that this tumor was not AT/RT but an
      astrocytic tumor with rhabdoid features. We also concluded that the tumor cells
      exhibiting rhabdoid features had secondarily arisen from the peripheral area
      presenting an appearance of diffuse astrocytoma.

PMID- 19408095
TI  - Pleomorphic xanthoastrocytoma as a component of a temporal lobe cystic
      ganglioglioma: a case report.
AB  - We report a case of pleomorphic xanthoastrocytoma (PXA) as a component of a
      ganglioglioma in a 13-year-old Japanese boy. Magnetic resonance imaging showed a
      large cystic lesion with an enhanced mural nodule of the left temporal lobe.
      Microscopic examination of the tumor showed that it was composed of two distinct
      neoplastic components: dysplastic ganglion cells and a PXA. There were gradual
      transitions between the two neoplastic components, and the PXA constituted the
      gliomatous component of the ganglioglioma. The PXA component showed spindle
      shaped and pleomorphic large cells with lipidized cytoplasm. The tumor cells were
      surrounded by numerous reticulin fibers. Immunohistochemically, the ganglion
      cells were negative for glial fibrillary acidic protein (GFAP), but showed
      positive staining for a 70-kDa neurofilament protein, synaptophysin, and NeuN. In
      contrast, PXA cells were positive for GFAP but negative for neuronal markers. Our
      case is therefore histologically classified as ganglioglioma with PXA as the
      glial component. These results suggested that PXA and ganglioglioma share a
      common origin and that the combination of PXA-ganglioglioma would be positioned
      along the spectrum between PXA and ganglioglioma. Alternatively, these results
      may support the hypothesis that PXA originates from glioneuronal progenitor cells
      capable of generating astrocytic and neuronal cell types.

PMID- 19408094
TI  - A case of a heavily pigmented orbital melanocytoma.
AB  - We present an extremely rare case of an orbital melanocytoma that occurred in a
      51-year-old man. The patient suffered from diplopia and mild exophthalmos of the
      right eye for 2 months. Brain magnetic resonance imaging showed a well-demarcated
      round mass 3.5 cm in diameter in the right orbit. We performed total resection of
      this tumor. Histological findings revealed a proliferation of large polygonal
      cells with fine pigment granules in the cytoplasm and prominent nucleoli.
      Although these tumor cells revealed immunohistochemical reactivity in HMB-1,
      there was no S-100 or Melan A antibody reactivity. Also, there were no malignant
      findings of nuclear polymorphism, mitoses, or necrosis. The brown pigments were
      confirmed to be melanin by bleaching and the Fontana-Masson silver stain method.
      The MIB-1 labeling index was less than 1%. This tumor also consisted of 50%
      melanophages, which revealed immunohistochemical reactivity in CD68, CD163, and
      in (1-AT antibodies. These histological findings led us to diagnose an orbital
      melanocytoma with partial tumor regression.

PMID- 19408096
TI  - Ultrastructural and immunohistochemical study of an adult case of chordoid
      meningioma.
AB  - A 64-year-old male patient presented with generalized convulsions. Magnetic
      resonance imaging revealed a large meningeal tumor with some cysts in the right
      frontal region. Surgical resections were performed three times, and local
      radiation therapy was administered twice over a period of 8 years for the
      treatment of tumor recurrences. The tumor tended to recur in spite of the
      surgical and radiation therapies. The tumor was diagnosed as a chordoid
      meningioma, and the second surgical specimen showed increasing nuclear atypia and
      mitoses in tumor cells. An immunohistochemical study revealed the tumor cells
      were positive for vimentin, S-100 protein, and cytokeratin AE1/AE3. An electron
      microscopic study revealed intracytoplasmic vacuolar spaces, loosely connected
      interdigitating cell processes with intermediate junctions, and extracellular
      spaces which contained fluffy granular intercellular substances. The tumor cell
      surfaces displayed pseudopodia which extended into the intercellular spaces and
      the tumor cells had moderate quantities of cytoplasm containing abundant
      mitochondria and glycogen granules. According to the ultrastructural features in
      the past reports of chordoid meningiomas, these meningiomas are suspected to have
      a mixture of the characteristic ultrastructural features of meningothelial
      meningiomas and chordoid sarcomas.

PMID- 19408097
TI  - Safety and adequacy of a semi-elemental formula for children with gastro
      intestinal disease.
AB  - A prospective, open trial was conducted to evaluate the nutritional adequacy of a
      semi-elemental diet in 47 children with functional gastro-intestinal disorders.
      Nutritional adequacy was assessed based on growth relative to Euro-growth
      standards for body mass index (BMI)-for-age z-scores and evaluations of blood
      parameters. Twenty-five patients completed the study. In total, 533 l of "New
      Alfare" was consumed during 775 trial-days. The mean intake per infant was 85.8
      +/- 26.8 kcal/kg/day or 122.5 +/- 38.3 ml/kg/day. Weight and length evolution
      during the 4 weeks trial were within normal range. The mean BMI-for-age z-score
      (P < 0.05) and albumin concentration (P < 0.01) increased significantly after 4
      weeks. Plasma threonine concentration decreased significantly (P = 0.01) and the
      tryptophan concentration increased (P = 0.06). No adverse events related to the
      study formula were reported. These results show that "New Alfare" is safe and
      nutritionally adequate for pediatric patients with gastro-intestinal disease.

PMID- 19408099
TI  - Low levels of serum vitronectin associated with clinical phases in patients with
      hemorrhagic fever with renal syndrome.
AB  - beta(3) integrin has been identified as a cellular receptor for Hantaan virus
      which causes hemorrhagic fever with renal syndrome (HFRS). As one of the ligands
      of beta(3) integrin, vitronectin (VN) may be altered in HFRS. In this study,
      changes of serum VN levels were determined in 112 patients with HFRS and 30 age-
      and sex-matched healthy controls by quantitative sandwich enzyme immunoassay. The
      levels of serum VN were analyzed in patients at various phases of HFRS and with
      different severity of clinical types. Serum VN levels in patients with HFRS, at
      all clinical phases except the convalescent phase, were significantly decreased
      compared with those in the controls (P < 0.01). The serum levels of VN decreased
      at febrile phase, maintained at the lowest status during hypotensive and oliguric
      phases, started to increase from polyuric phase and reached almost normal
      condition till convalescent phase. The levels of serum VN between patients with
      milder and more severe clinical types showed no significant difference at each
      phase (P > 0.05). These results suggest that VN level was altered during the
      course of HFRS and chronological changes of serum levels of VN may correlate with
      the evolution of the disease.

PMID- 19408100
TI  - Mannose-binding lectin polymorphisms in common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous group of disorders,
      characterized by hypogammaglobulinemia and increased susceptibility to
      infections, autoimmunity and malignancies. This study was performed to analyze
      the Mannose-binding lectin (MBL) polymorphisms in Iranian patients with CVID.
      Thirty-five CVID patients who were treated at Children's Medical Center and 100
      matched controls were enrolled in this study. Sixth single-nucleotide
      polymorphisms of the MBL gene were analyzed using PCR-SSP method. Comparison of
      MBL exon 1 coding alleles between patients and controls revealed that A allele
      (wild-type) was significantly decreased in CVID group, whereas B allele was
      overrepresented in the patient group. High frequency of heterozygous (A/O) in the
      patient group and high frequency of homozygous for wild-type coding regions in
      the control group were detected. Comparison of MBL haplotype promoters between
      CVID patients and controls showed that LYPB haplotype was significantly
      overrepresented in the CVID group. Mutant and low-producing MBL alleles and
      haplotypes might reflect as an associated genetic factor in CVID patients, which
      could play as a susceptibility factor in CVID.

PMID- 19408098
TI  - Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and
      obesity.
AB  - Several polymorphisms in apolipoprotein A1 (APOA1) gene have been associated with
      metabolic diseases. Increased transcription efficiency was observed in -75A
      allele carriers compared to -75G allele homozygotes. +83C allele was associated
      with higher body mass index and waist-to-hip ratio in type II diabetes subjects. 
      75G/A and +83C/T polymorphisms were analyzed by RFLP-PCR in 334 individuals from
      a Brazilian elderly cohort. APOA1 polymorphisms were associated with age-related
      morbidities, as well as with triglycerides, total cholesterol, HDL, VLDL, LDL,
      creatinine, urea, albumin, glycated hemoglobin and fasting glucose serum levels.
      Allele frequencies were 0.102 and 0.21, respectively, for -75A and +83T. -75G
      allele showed significant association with hypertension (P = 0.001). An
      association between +83C allele and obesity was observed (P = 0.040) and this
      allele also showed an association with hypertension in the presence of
      cardiovascular disease (P = 0.047). Moreover, +83T allele was associated with
      lower glycated hemoglobin values (P = 0.026). To our knowledge, there is no data
      associating this polymorphism with glycated hemoglobin. Furthermore, individuals
      carrying AT haplotype have lower risk for developing hypertension (P = 0.0002),
      while GT haplotype carriers present decreased risk to develop obesity comparing
      to GC haplotype (P = 0.025). APOA1 polymorphisms analysis may be a useful tool to
      identify risk factors for subjects and families and clarify the
      physiopathological role of these polymorphisms in age-related diseases, such as
      hypertension and obesity.

PMID- 19408101
TI  - Sir Frank Macfarlane Burnet and the clonal selection theory of antibody
      formation.
AB  - Sir Macfarlane Burnet has been one of the twentieth century's outstanding
      biologists. In the years 1941-1956, Burnet focused his effort on the elaboration
      of a theory of antibody synthesis, the clonal selection theory, capable of
      bridging the gap between physiological findings, such as the kinetics of antibody
      production, self-tolerance and immunological memory on the one hand, and the
      newest ideas on synthesis of proteins, on the other. At the time of writing the
      clonal selection theory, Burnet was 57 years old and the Director of the Water
      and Eliza Hall Institute in Melbourne, Australia.

PMID- 19408103
TI  - Acute effects of positive end-expiratory pressure on left ventricle diastolic
      function in healthy subjects.
AB  - We evaluated the acute effect of the application of positive end-expiratory
      pressure (PEEP) on LV diastolic function in 10 healthy subjects. We assessed load
      dependent diastolic function by Doppler examination of transmitral flow and load
      independent diastolic function by color M-mode propagation velocity of early flow
      into the LV cavity (Vp). During the application of PEEP in comparison to the
      baseline, we found a significant reduction of the E wave peak velocity [79 (64
      83) vs. 65 (57-72) cm/s; p = 0.028] and a significant reduction in Vp [84 (73-97)
      vs. 53 (48-66); p = 0.012]. Moreover, we found a significant reduction in left
      atrial area [15 (13-18) vs. 12 (10-14) cm(2); p = 0.018] and right atrial area
      [12 (11-15) vs. 11 (9-12) cm(2); p = 0.015]. No difference was found in global LV
      systolic function. The application of PEEP acutely modifies the diastolic flow
      pattern across the mitral valve, and reduces atrial dimensions.

PMID- 19408102
TI  - Cancer therapy using tumor-associated antigens to reduce side effects.
AB  - Tumor-associated antigens recently have become very popular in cancer therapy.
      They can be targeted to reduce side effects of traditional cancer therapy. In
      this review, ten promising tumor-associated antigens are being discussed in
      detail. The characteristics of each one are being reviewed in detail. Monoclonal
      antibodies attached to traditional anticancer agents can target a specific type
      of cancer cells thereby reducing the amount of traditional anticancer agents
      reaching normal tissues. This sort of cancer targeting can be a very attractive
      anticancer therapy because it substantially reduces the amount of side effects
      normally caused by traditional anticancer agents.

PMID- 19408104
TI  - Differentiation of the mammary epithelial cell during involution: implications
      for breast cancer.
AB  - That milk secretion is not the final differentiated state of the mammary alveolar
      cells is a relatively new concept. Recent work has suggested that secreting,
      mammary epithelial cells (MECs) have another function to perform before they
      undergo cell death in the involuting mammary gland. That is, they help in the
      final clearance and breakdown of their neighboring cells (and likely residual
      milk as well.) They become, for a short time, amateur phagocytes, or efferocytes,
      and then are believed to die and be cleared themselves. Although relatively
      little study has been made of this change in the functional state of the MEC,
      nevertheless we may speculate from the involution literature, and extend findings
      from other systems of apoptotic cell clearance, on some of the mechanisms
      involved. And with the finding that involution may represent a unique
      susceptibility window for the progression of metastatic breast cancer, we may
      suggest areas for future research along these lines as well.

PMID- 19408105
TI  - A mouse mammary gland involution mRNA signature identifies biological pathways
      potentially associated with breast cancer metastasis.
AB  - Mouse mammary gland involution resembles a wound healing response with suppressed
      inflammation. Wound healing and inflammation are also associated with tumour
      development, and a 'wound-healing' gene expression signature can predict
      metastasis formation and survival. Recent studies have shown that an involuting
      mammary gland stroma can promote metastasis. It could therefore be hypothesised
      that gene expression signatures from an involuting mouse mammary gland may
      provide new insights into the physiological pathways that promote breast cancer
      progression. Indeed, using the HOPACH clustering method, the human orthologues of
      genes that were differentially regulated at day 3 of mammary gland involution and
      showed prolonged expression throughout the first 4 days of involution
      distinguished breast cancers in the NKI 295 breast cancer dataset with low and
      high metastatic activity. Most strikingly, genes associated with copper ion
      homeostasis and with HIF-1 promoter binding sites were the most over-represented,
      linking this signature to hypoxia. Further, six out of the ten mRNAs with
      strongest up-regulation in cancers with poor survival code for secreted factors,
      identifying potential candidates that may be involved in stromal/matrix-enhanced
      metastasis formation/breast cancer development. This method therefore identified
      biological processes that occur during mammary gland involution, which may be
      critical in promoting breast cancer metastasis that could form a basis for future
      investigation, and supports a role for copper in breast cancer development.

PMID- 19408106
TI  - Simultaneous determination of labetalol and furosemide by first-derivative
      synchronous spectrofluorimetry.
AB  - A rapid, simple and highly sensitive first derivative synchronous
      spectrofluorimetric method was developed for the simultaneous analysis of a
      binary mixture of labetalol HCl (LBT) and furosemide (FUR) without prior
      separation. The method was based upon measuring the first derivative of
      synchronous fluorescence spectra of the two drugs at Deltalambda = 130 nm in
      aqueous ethanol (55% V/V). The different experimental parameters affecting the
      synchronous fluorescence of the studied drugs were carefully studied and
      optimized. The first derivative amplitude-concentration plots were rectilinear
      over the range of 0.10 to 1.00 microg/mL and 0.05-0.50 microg/mL with lower
      detection limits of 0.0149 and 7 x 10(-3) microg/mL and quantification limits of
      0.045 and 0.021 microg/mL for LBT and FUR, respectively. The proposed method was
      successfully applied for the determination of the studied drugs in synthetic
      mixtures. The results obtained were in good agreement with those obtained by the
      reference methods.

PMID- 19408109
TI  - Intracultural variation in cross-cultural gerontology.

PMID- 19408107
TI  - NK and NKT cells in aging and longevity: role of zinc and metallothioneins.
AB  - INTRODUCTION: During aging, dysregulated immune functions occur contributing to
      increased susceptibility to morbidity and mortality. However, these
      dysregulations are normally counterbalanced by continuous adaptation of the body
      to the deteriorative changes occurring over time. These adaptive changes well
      occur in healthy centenarians. DISCUSSION: Both innate (natural) and adaptive
      (acquired) immune responses decline with advancing age. Natural killer (NK) and
      natural killer T (NKT) cell cytotoxicity, representing one of best models of
      innate immune response, decreases in aging as well as interferon-gamma (IFN
      gamma) production by both activated types of cells. Both NK and NKT cell
      cytotoxicity and IFN-gamma production increase in very old age with respect to
      normal aging, especially by NKT cells bearing TCRgammadelta. The role played by
      zinc and metallothioneins (MT) is crucial because this affects NK and NKT cell
      development, maturation, and functions. In particular, some MT polymorphisms are
      involved in maintaining innate immune response and intracellular zinc ion
      availability in aging with thus a role of MT genetic background to escape some
      age-related diseases with subsequent healthy aging and longevity.

PMID- 19408110
TI  - Ballpen into the bladder of a woman due to sexual practice.

PMID- 19408111
TI  - Methodological issues for studying asexuality.

PMID- 19408108
TI  - NF-kappaB signaling in the aging process.
AB  - INTRODUCTION: The aging process represents a progressive decline in cellular and
      organism function. Explaining the aging process has given rise to a cornucopia
      for different theories in which the basic difference has been the question
      whether aging is genetically regulated or an entropic degeneration process.
      DISCUSSION: Different screening techniques have revealed that mammalian aging is
      associated with the activation of NF-kappaB transcription factor system. The NF
      kappaB system is an ancient host defense system concerned with immune responses
      and different external and internal dangers, such as oxidative and genotoxic
      stress. NF-kappaB signaling is not only the master regulator of inflammatory
      responses but can also regulate several homeostatic responses such as apoptosis,
      autophagy, and tissue atrophy. We will describe how chronic activation of NF
      kappaB signaling has the capacity to induce the senescent phenotype associated
      with aging. Interestingly, several longevity genes such as SIRT1, SIRT6, and
      FoxOs can clearly suppress NF-kappaB signaling and in this way delay the aging
      process and extend lifespan. CONCLUSION: It seems that the aging process is an
      entropic degeneration process driven by NF-kappaB signaling. This process can be
      regulated by a variety of longevity genes along with a plethora of other factors
      such as genetic polymorphism, immune and dietary aspects, and environmental
      insults.

PMID- 19408112
TI  - Detecting functional connectivity in fMRI using PCA and regression analysis.
AB  - A fMRI connectivity analysis approach combining principal component analysis
      (PCA) and regression analysis is proposed to detect functional connectivity
      between the brain regions. By first using PCA to identify clusters within the
      vectors of fMRI time series, more energy and information features in the signal
      can be maintained than using averaged values from brain regions of interest.
      Then, regression analysis can be applied to the extracted principal components in
      order to further investigate functional connectivity. Finally, t-test is applied
      and the patterns with t-values lager than a threshold are considered as
      functional connectivity mappings. The validity and reliability of the presented
      method were demonstrated with both simulated data and human fMRI data obtained
      during behavioral task and resting state. Compared to the conventional functional
      connectivity methods such as average signal based correlation analysis,
      independent component analysis (ICA) and PCA, the proposed method achieves
      competitive performance with greater accuracy and true positive rate (TPR).
      Furthermore, the 'default mode' and motor network results of resting-state fMRI
      data indicate that using PCA may improve upon application of existing regression
      analysis methods in study of human brain functional connectivity.

PMID- 19408113
TI  - Executive functions in children: associations with aggressive behavior and
      appraisal processing.
AB  - This study investigated whether and how deficits in executive functioning and
      distortions in appraisal processing are related to subtypes of aggressive
      behavior. The sample included 83 boys assessed using multi-informant reports and
      performance measures. Deficits in two executive functions, response inhibition
      and planning ability were related primarily to reactive aggression. Hostile
      attributional biases moderated relations between planning ability and proactive
      and reactive aggression subtypes, with minimal relations between planning
      deficits and aggression at low levels of hostile attributional bias. As the level
      of hostile attributional bias increased, the relation between planning deficits
      and reactive aggression became increasingly large in a positive direction whereas
      the relation between planning deficits and proactive aggression became
      increasingly negative. Additionally, hostile encoding moderated the relation
      between behavioral inhibition and reactive aggressive behavior. Results also
      suggested a mediational role for response inhibition in the relation between
      planning ability and reactive aggression.

PMID- 19408114
TI  - The effect of soft budget constraints on access and quality in hospital care.
AB  - Given an increasingly complex web of financial pressures on providers, studies
      have examined how hospitals' overall financial health affects different aspects
      of hospital operations. In our study, we develop an empirical proxy for the
      concept of soft budget constraint (SBC, Kornai, Kyklos 39:3-30, 1986) as an
      alternative financial measure of a hospital's overall financial health and offer
      an initial estimate of the effect of SBCs on hospital access and quality. An
      organization has a SBC if it can expect to be bailed out rather than shut down.
      Our conceptual model predicts that hospitals facing softer budget constraints
      will be associated with less aggressive cost control, and their quality may be
      better or worse, depending on the scope for damage to quality from
      noncontractible aspects of cost control. We find that hospitals with softer
      budget constraints are less likely to shut down safety net services. In addition,
      hospitals with softer budget constraints appear to have better mortality outcomes
      for elderly heart attack patients.

PMID- 19408117
TI  - Massive extra-adrenal retroperitoneal paraganglioma: pre-operative embolization
      and resection.

PMID- 19408116
TI  - Beliefs about causes of schizophrenia among police officers before and after
      crisis intervention team training.
AB  - This study examined the ways in which beliefs about the causes of schizophrenia
      change after crisis intervention team (CIT) training of police officers.
      Comparisons of pre- and post-training scores from 159 officers revealed a
      decrease in endorsement of items pertaining to personal/family/social stressors
      and items inconsistent with contemporary conceptions of risk, as well as an
      increase in endorsement of items consistent with modern biological conceptions of
      the causation of schizophrenia. Changes in causal beliefs were associated with
      personal and family history of psychiatric treatment among officers. Findings
      indicate a need for further research in this area, and suggest that some
      characteristics of officers may be associated with an increased capacity for
      knowledge/attitudinal change during CIT training.

PMID- 19408115
TI  - Cruciferous nutraceutical 3H-1,2-dithiole-3-thione protects human primary
      astrocytes against neurocytotoxicity elicited by MPTP, MPP(+), 6-OHDA, HNE and
      acrolein.
AB  - Astrocytes possess important roles in maintaining normal brain function and
      providing trophic support to the neurons. They also suffer a range of toxic
      insults, being a chief target of prooxidants such as 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP(+)), 6
      hydroxydopamine (6-OHDA), 4-hydroxy-2-nonenal (HNE), and acrolein. Recently, we
      have observed that the cellular antioxidants and phase 2 enzymes can be
      upregulated by 3H-1,2-dithiole-3-thione (D3T), a nutraceutical found in
      cruciferous vegetables, against many prooxidants in human neuroblastoma cell
      lines (SH-SY5Y). However, the regulation of the above cellular factors by D3T in
      astrocytes and their role in ameliorating the neurotoxic effects of the above
      neurotoxins have not been investigated. In this study, we show that incubation of
      human primary astrocytes with micromolar concentrations (5-100 microM) of D3T for
      24 h resulted in significant increases in the levels of reduced glutathione
      (GSH), glutathione reductase (GR), and the phase 2 enzyme NAD(P)H:quinone
      oxidoreductase 1 (NQO1). D3T treatment also caused time-dependent increases in
      mRNA expression of the gamma-glutamylcysteine ligase catalytic subunit (GCLC),
      GR, and of NQO1 in these cells. Pretreatment of astrocytes with D3T was found to
      afford remarkable protection against the neurocytotoxicity elicited by MPTP,
      MPP(+), 6-OHDA, HNE and acrolein. Taken together, this study demonstrates for the
      first time that in human astrocytes, the cruciferous nutraceutical D3T potently
      induces the cellular GSH system and the phase 2 enzyme NQO1, which is accompanied
      by dramatically increased resistance of these cells to the damage induced by
      various neurotoxicants. The results of this study may have important implications
      for the development of novel neuroprotective strategies.

PMID- 19408119
TI  - Detection of depression with different interpreting methods among Chinese and
      Latino primary care patients: a randomized controlled trial.
AB  - Language barriers may contribute to the under-detection of depression in Latinos
      and Asians. A total of 782 English, Spanish, and Chinese-speaking primary care
      patients were enrolled in a randomized controlled trial. Language discordant
      patients were randomized to Remote Simultaneous Medical Interpreting (RSMI) or
      usual and customary (U&C) interpreting. The Beck Depression Inventory-Fast Screen
      (BDI-FS) was administered. Patients were tracked for 1 year. A total of 462
      patients completed the BDI-FS. Thirty-three percent had a positive (> or = 4)
      screen. Twenty-seven percent of BDI-FS positive patients were diagnosed with
      depression. Among BDI-FS positive patients, Chinese-speakers were less likely to
      be diagnosed compared with English speakers (31% vs. 10%, P < 0.05). There was a
      trend towards greater diagnosis with RSMI (27% detection with RSMI vs. 20% U&C, P
      = 0.41). The diagnosis of depression among BDI-FS positive patients in our
      population was low, particularly among Chinese-speakers. RSMI could be an
      important part of a multi-faceted approach to improving the detection of
      depression.

PMID- 19408118
TI  - A proposed role for the psychiatrist in the treatment of adolescents with type I
      diabetes.
AB  - Type I diabetes is a chronic illness that most frequently develops during
      childhood. As a medical doctor with an understanding of psychology and human
      development, the psychiatrist is in a unique position to guide the child or
      adolescent with diabetes and his family through the typical lifestyle adjustments
      that are encountered when diagnosed with diabetes. This article presents an
      overview of the diagnosis and management of type I diabetes, reviews the ways in
      which diabetes will interact with child development, and discusses the increased
      rates of eating disorders and mood disorders among children with type I diabetes.
      There is a distinct role for the psychiatrist to be involved in the diabetes care
      team of children and adolescents diagnosed with type I diabetes and this role can
      be medically crucial.

PMID- 19408120
TI  - Evaluation of human endothelial cells post stent deployment in a cardiovascular
      simulator in vitro.
AB  - Percutaneous stent implantation has revolutionized the clinical treatment of
      occluded arteries. Nevertheless, there is still a large unmet need to prevent re
      occlusion after implantation. Consequently, a niche exists for a cost-effective
      pre-clinical method of evaluating novel interventional devices in human models.
      Therefore, the development of a coronary model artery offers tremendous potential
      for the treatment of endothelial cell dysfunction and restenosis. As a first
      step, we employ tissue-engineering principles to examine the effect of stent
      deployment upon endothelial cells in a tubular in vitro system capable of
      replicating the coronary artery biomechanical environment. In particular, the
      cellular and molecular changes pertaining to inflammation, proliferation, and
      death were assessed after stent deployment. Real-time quantitative PCR
      demonstrated increased expression of genes encoding for E-Selectin, ICAM-1, and
      VCAM-1; markers associated with an inflammatory response in vivo. Further, an
      increase in the pro-apoptotic protein Bax was paralleled with a decrease in the
      anti-apoptotic protein Bcl-2; however, apoptotic morphology was not observed.
      Interestingly, transcription of c-fos increased, whereas Ki67 levels fell over
      the same period. One hypothesis is that these results are in response to the
      altered local hemodynamic environment induced by stent deployment. Most
      significantly, this study highlights the potential of a biomimetic hemodynamic
      bioreactor combined with a gene expression analysis to evaluate, with greater
      specificity, the performance and interaction of stents with the endothelial layer
      in a controlled environment.

PMID- 19408121
TI  - Acculturation and substance use among Hispanic early adolescents: investigating
      the mediating roles of acculturative stress and self-esteem.
AB  - We examined the extent to which Hispanic orientation and American orientation are
      associated with substance use (cigarette, alcohol, and marijuana) both directly
      and indirectly through acculturative stress and self-esteem. Participants were
      347 Hispanic early adolescents (50.7% male; mean age = 12.57, SD = 0.92, range 11
      15) from two middle schools in western Michigan. Findings showed that self-esteem
      emerged as the most consistent predictor of likelihood and extent of substance
      use. Ethnic identity was positively related to risk for substance use, and
      acculturative stress and self-esteem mediated the relationships of Hispanic
      cultural orientation to alcohol use. Self-esteem was the most important
      protective factor against substance use, and as such, we conclude that prevention
      programs designed to address precocious substance use that incorporate a self
      esteem building component could prove useful among Hispanic early adolescents
      residing in monocultural contexts within the United States.

PMID- 19408122
TI  - Family mediators of acculturation and adolescent sexual behavior among Latino
      youth.
AB  - The present study develops and evaluates a theoretical framework of mediators of
      the relationship between acculturation and adolescent sexual behavior. Four
      hundred Latino mother-adolescent dyads from the Bronx, New York were interviewed.
      The study explored the relationship between intentions to have sexual intercourse
      and explanatory variables such as adolescent romantic relationship status and
      partner preferences, maternal approval of dating, adolescent perceptions of
      maternal approval of dating, and maternal and adolescent levels of familismo and
      acculturation. Findings revealed complex dynamics between acculturation and
      adolescent sexual behavior. Protective and risk-inducing associations were
      observed, with important gender differences operating for boys and girls.
      Implications for the development of applied prevention programs are discussed.

PMID- 19408123
TI  - Entre dos mundos/between two worlds: bicultural development in context.
AB  - How do Mexican immigrant adolescents balance different, and often oppositional,
      cultural influences in the acculturation process? In this article, we explore how
      acculturating adolescents absorb cultural messages and go about creating their
      (multiple) identities. Guided by Alternation Theory, in-depth qualitative
      interviews were conducted with 12 undocumented Mexican adolescents and 14 of
      their parents who had immigrated to North Carolina within the past 7 years. All
      of the families had adolescent children who were born in Mexico. At least one
      parent and one adolescent from each family were interviewed. Interviewing
      multiple family members allowed us to examine how bicultural development
      progressed differently for various family members, and how the whole family
      balanced between cultural systems. Mexican parents and adolescents were
      acculturating while trying to resist assimilation pressures. They maintained
      strong Mexican identities that were preserved by practicing Mexican customs,
      values, and traditions in their homes and churches. Meeting U.S. cultural and
      linguistic demands at work and in school placed Mexican parents and adolescents
      between the two cultural systems. This prompted adolescents and parents to
      integrate some U.S. customs, language, or social behaviors into their daily
      lives, increasing bilingualism and, in some cases, biculturalism.

PMID- 19408124
TI  - The impact of acculturative stress and daily hassles on pre-adolescent
      psychological adjustment: examining anxiety symptoms.
AB  - Acculturative stress in relation to anxiety symptoms has not been examined
      empirically in young Hispanic populations. The present study, conducted with 138
      pre-adolescent Hispanic youngsters, investigated this relationship. The findings
      suggested that acculturative stress was related to physiological, concentration,
      and worrisome symptoms of anxiety. After decomposing acculturative stress, it
      became evident that perceived discrimination accounted for a large proportion of
      the variance in the relationship between acculturative stress and anxiety.
      Immigration-related stress was mostly associated with worry symptoms. Finally,
      total daily hassles were an independent predictor of concentration and
      physiological anxiety symptoms. Implications for prevention interventions and
      future research are discussed.

PMID- 19408125
TI  - The ancient Greek philosopher, Heraclitus. Editorial.

PMID- 19408126
TI  - Glycogen synthase kinase-3beta regulates etoposide-induced apoptosis via Bcl-2
      mediated caspase-3 activation in C3H10T1/2 cells.
AB  - Glycogen synthase kinase-3beta (GSK3beta) controls the survival of osteoblasts
      during bone development through Wnt canonical signaling. GSK3beta is a key factor
      for osteoblastogenesis, but relatively less is known regarding its role in
      osteoblast apoptosis. Genotoxic stress induced by etoposide promoted apoptotic
      signaling by GSK3beta activation in C3H10T1/2 cells, a mouse mesenchymal cell
      line. Etoposide led to the time-dependent activation of GSK3beta and caspase-3,
      which resulted in PARP cleavage. LiCl (a specific inhibitor) and siRNA (gene
      knock-down) of GSK3beta prevented the effects of etoposide on apoptosis.
      Staurosporine also induced apoptosis in C3H10T1/2 cells, but LiCl could not
      rescue. Bcl-2 was decreased in the cells by exposure to etoposide. LiCl
      completely recovered Bcl-2 expression as shown by both the mRNA and the protein
      expression levels. In conclusion, etoposide-induced apoptosis in C3H10T1/2 cells
      is mediated by GSK3beta, which leads to caspase-3 activation via decrease in Bcl
      2 expression.

PMID- 19408127
TI  - Pituicytoma and isolated ACTH deficiency.

PMID- 19408128
TI  - Evaluation of insulin sensitivity in hyperprolactinemic subjects by euglycemic
      hyperinsulinemic clamp technique.
AB  - The background and aim of the study is to evaluate insulin sensitivity in
      hyperprolactinemic subjects via euglycemic hyperinsulinemic clamp technique.
      Sixteen hyperprolactinemic subjects and 12 healthy subjects were included in the
      study. HOMA-B and HOMA-IR values of groups were calculated. Euglycemic
      hyperinsulinemic clamp technique was performed in both groups, and the M value of
      the groups was defined. Mann-Whitney U and chi-square tests were used in
      statistical analysis. Basal insulin level of hyperprolactinemic patients were
      higher than the control group (6.85 +/- 4.68; 3.66 +/- 0.88 microU/ml
      respectively; P < 0.05). Mean HOMA-IR and HOMA-B values of patients were higher
      than control group (1.49 +/- 1.30; 0.78 +/- 0.27 respectively; P = 0.02 and
      136.28 +/- 72.53; 64.77 +/- 23.31, respectively, P < 0.001). M values of the
      patients were statistically lower than the control group (5.64 +/- 2.36; 7.05 +/-
      1.62 kg/mg/min respectively; P < 0.05). (1) Hyperprolactinemic patients were more
      insulin resistant than control subjects. (2) Insulin resistance in
      hyperprolactinemic patients is not associated with obesity or anthropometric
      parameters such as fat content, waist circumference and BMI.

PMID- 19408129
TI  - Systemic therapy of advanced urothelial cancer.
AB  - Advanced bladder/urothelial cancer remains an incurable terminal disease, and
      accounts for 3% of the cancer related mortality in the United States. Systemic
      chemotherapy achieves palliation, survival benefit, and occasional long-term
      remissions. The two regimens that have been widely adopted consist of either
      cisplatin and gemcitabine, or the MVAC (methotrexate, vinblastine, doxorubicin
      and cisplatin) regimen. Novel therapies are being evaluated in metastatic bladder
      cancer to improve survival outcomes. A randomized trial of larotaxel (a novel
      taxane) and cisplatin vs cisplatin and gemcitabine in frontline therapy of
      metastatic urothelial cancer is ongoing. The studies evaluating therapies
      targeted frontline involve cisplatin and gemcitabine with or without cetuximab
      (ongoing), and with or without bevacizumab (CALGB proposed trial). With the
      advent of adjuvant/neoadjuvant cisplatin-based therapy, and improvement in
      supportive care, more patients are being considered for second-line therapies in
      urothelial cancer thus making this a field of emerging importance. The only phase
      III trial in pretreated urothelial cancer compared vinflunine with best
      supportive care, and revealed no significant survival improvement. Clinical
      trials are ongoing with pazopanib, a VEGF inhibitor, and Zactima, a VEGF and EGFR
      inhibitor. The biggest hurdle to progress in advanced bladder cancer has been the
      slow accrual to studies in the United States. Making clinical trial participation
      a priority in bladder cancer is the dire need of the moment. At the same time, it
      is essential to take into account the changing needs of the population afflicted
      with bladder cancer, and tailor the therapeutic trials to fit a contemporary
      patient.

PMID- 19408132
TI  - Common carp (Cyprinus carpio) response to two pieces of music ("Eine Kleine
      Nachtmusik" and "Romanza") combined with light intensity, using recirculating
      water system.
AB  - The objective of this study was to further investigate the effects of music on
      fish physiology, bearing in mind available information regarding the involvement
      of endogenous and exogenous factors in fish farming. Therefore, Cyprinus carpio
      (50.5 +/- 0.36 g) were reared in a recirculating water system under 80 and 200
      lux and subjected to no music at all (control, ambient noise only), 4 h of
      Mozart's "Eine Kleine Nachtmusik", or 4 h of anonymous "Romanza-Jeux Interdits"
      for 106 days. Both music treatments resulted in increased growth performance at
      both light intensities, with Romanza treatment at 200 lux resulting in better
      growth performance than Mozart treatment. Furthermore, feed efficiency for the
      Romanza groups was significantly better than for the control. Although no
      significant music effect was apparent for brain neurotransmitters, lower anterior
      intestine alkaline protease levels were detected for both music treatments.
      Taking into consideration the numerous advantages of recirculating water systems,
      it should be emphasised that fish response to music expresses the results of
      various physiological and biochemical processes, especially when fish notably
      respond differently when subjected to two different pieces of music.

PMID- 19408133
TI  - Extracorporeal membrane oxygenation in a patient with propionic acidaemia: a
      therapeutic option for cardiac failure.
AB  - We report a Japanese girl affected with a neonatal-onset form of propionic
      acidaemia (PA). She developed severe metabolic crisis after dehydration at 2
      years of age. Bradycardia with complete atrioventricular block responded to
      haemodiafiltration, but severe cardiac failure was refractory to inotropic
      treatment. She was diagnosed with acute cardiac dysfunction caused by PA-induced
      metabolic crisis. Extracorporeal membrane oxygenation (ECMO), a technique for
      providing mechanical circulatory support, was required. This is the first case
      report of a PA patient who recovered from a life-threatening metabolic crisis
      with cardiac failure by ECMO. Cardiac failure may be a cause of death, but it is
      occasionally an under-recognized complication. Mitochondrial dysfunction in the
      myocardium due to propionyl-CoA could contribute to the pathomechanism of cardiac
      complications of PA. We believe that ECMO should be attempted in PA patients with
      cardiac failure, in addition to haemodiafiltration and other therapeutic
      measures, because doing so may lead to the recovery of cardiac dysfunction, as
      was evident in our patient. In conclusion, prompt investigations and management
      of cardiac complications should be performed immediately during PA-induced
      metabolic crises.

PMID- 19408135
TI  - Role identification, community socio-economic status demands, and stress outcomes
      in police officers.
AB  - This study applied the 'job demands-resources' and 'conservation of resources'
      models to police work, with the specific aim to examine the possible interaction
      between objectively measured work demands (community socio-economic status (SES))
      and personal resources (role identification) on stress-related outcomes. A total
      of 89 officers from 10 small, suburban police departments (five from high SES
      areas and five from low SES areas) completed surveys that focused on community
      SES demands and role identification as factors that potentially influence
      positive and negative psychological outcomes. Results indicated that community
      (SES) demands and role identification interacted to predict a variety of the
      outcomes. Role identification as a psychological resource served to reduce the
      effects of high community SES demands on emotional exhaustion. Implications of
      these results for future police research are discussed.

PMID- 19408134
TI  - Sudden infant death syndrome and Ljungan virus.
AB  - Ljungan virus (LV) has recently been associated with perinatal death in its
      natural rodent reservoir and also with developmental disorders of reproduction in
      laboratory mice. A strong epidemiological association has been found between
      small rodent abundance in Sweden and the incidence of intrauterine fetal death
      (IUFD) in humans. LV antigen has been detected in half of the IUFD cases tested.
      The question was therefore raised whether sudden infant death syndrome (SIDS)
      might be associated with rodent abundance, and whether the virus is present in
      cases of SIDS. Variation in the incidence of SIDS using the Swedish cause-of
      death database tracked the changes in the population fluctuations of native
      rodents. Formalin-fixed tissues from the brain, heart, and lung were investigated
      from cases of SIDS, SIDS with lymphocytic infiltration of the myocardium
      (myocarditis) and myocarditis cases using LV specific immunohistochemistry (IHC).
      Ljungan virus was detected in the brain, heart, and lung tissue from all three of
      the patient categories investigated using IHC. These studies suggest that LV may
      play a prominent role in infant death, and that IUFD and SIDS may have common
      etiological underpinnings.

PMID- 19408136
TI  - Synthesis, characterization and in vitro activity of a surface-attached
      antimicrobial cationic peptide.
AB  - Infection associated with implanted biomaterials is common and costly and such
      infections are extremely resistant to antibiotics and host defenses.
      Consequently, there is a need to develop surfaces which resist bacterial adhesion
      and colonization. The broad spectrum synthetic cationic peptide melimine has been
      covalently linked to a surface via two azide linkers, 4-azidobenzoic acid (ABA)
      or 4-fluoro-3-nitrophenyl azide (FNA), and the resulting surfaces characterized
      by X-ray photoelectron spectroscopy and contact angle measurements. The quantity
      of bound peptide was estimated by a modified Bradford assay. The antimicrobial
      efficacy of the two melimine-modified surfaces against Pseudomonas aeruginosa and
      Staphylococcus aureus was compared by scanning electron microscopy (SEM) and
      fluorescence microscopy. Attachment of melimine via ABA gave an approximately 4
      fold greater quantity of melimine bound to the surface than attachment via FNA.
      Surfaces melimine-modified by either attachment strategy showed significantly
      reduced bacterial adhesion for both strains of bacteria. P. aeruginosa exposed to
      ABA-melimine and FNA-melimine surfaces showed marked changes in cell morphology
      when observed by SEM and a reduction of approximately 15-fold (p < 0.001) in the
      numbers of adherent bacteria compared to controls. For the ABA-melimine surface
      there was a 33% increase in cells showing damaged membranes (p = 0.0016) while
      for FNA-melimine there was no significant difference. For S. aureus there were
      reductions in bacterial adhesion of approximately 40-fold (p < 0.0001) and 5-fold
      (p = 0.008) for surfaces modified with melimine via ABA or FNA, respectively.
      There was an increase in cells showing damaged membranes on ABA-melimine surfaces
      of approximately 87% (p = 0.001) compared to controls, while for FNA-melimine
      there was no significant difference observed. The data presented in this study
      show that melimine has excellent potential for development as a broad spectrum
      antimicrobial coating for biomaterial surfaces. Further, it was observed that the
      efficacy of antimicrobial activity is related to the method of attachment.

PMID- 19408137
TI  - Phenotypic and genetic differences between opaque and translucent colonies of
      Vibrio alginolyticus.
AB  - Many pathogens undergo phase variation between rugose and smooth colony
      morphology or between opaque and translucent colony morphology, which is mainly
      due to the variation in the surface polysaccharides. In this study, Vibrio
      alginolyticus ZJ-51 displayed phase variation between opaque, rugose colonies
      (Op) and translucent, smooth colonies (Tr). Unlike the vibrios reported
      previously, Tr cells of ZJ-51 enhanced biofilm formation and motility, but they
      did not differ from Op cells in the quantity of surface polysaccharides produced.
      Real time PCR was used to analyze the expression of the genes involved in
      polysaccharide biosynthesis, flagellar synthesis, and the AI-2 quorum-sensing
      system. The results revealed that the K-antigen capsule gene cluster (which
      consists of homologs to the cpsA-K in Vibrio parahaemolyticus) and O-antigen
      polysaccharide gene cluster (which contains homologs to the wza-wzb-wzc) were
      significantly more transcribed in Tr cells. The AI-2 quorum-sensing genes showed
      enhanced expression in the Tr variant which also exhibited greater expression of
      genes associated with polar flagellar biosynthesis. These results suggest that
      colony phase variation might affect the virulence and survival ability in the
      stressful environment inhabited by V. alginolyticus.

PMID- 19408138
TI  - Ambulatory estimation of mean step length during unconstrained walking by means
      of COG accelerometry.
AB  - It has been reported that spatio-temporal gait parameters can be estimated using
      an accelerometer to calculate the vertical displacement of the body's centre of
      gravity. This method has the potential to produce realistic ambulatory
      estimations of those parameters during unconstrained walking. In this work, we
      want to evaluate the crude estimations of mean step length so obtained, for their
      possible application in the construction of an ambulatory walking distance
      measurement device. Two methods have been tested with a set of volunteers in 20 m
      excursions. Experimental results show that estimations of walking distance can be
      obtained with sufficient accuracy and precision for most practical applications
      (errors of 3.66 +/- 6.24 and 0.96 +/- 5.55%), the main difficulty being inter
      individual variability (biggest deviations of 19.70 and 15.09% for each
      estimator). Also, the results indicate that an inverted pendulum model for the
      displacement during the single stance phase, and a constant displacement per step
      during double stance, constitute a valid model for the travelled distance with no
      need of further adjustments. It allows us to explain the main part of the
      erroneous distance estimations in different subjects as caused by fundamental
      limitations of the simple inverted pendulum approach.

PMID- 19408130
TI  - Prediction of hepatic clearance in human from in vitro data for successful drug
      development.
AB  - The in vivo metabolic clearance in human has been successfully predicted by using
      in vitro data of metabolic stability in cryopreserved preparations of human
      hepatocytes. In the predictions by human hepatocytes, the systematic
      underpredictions of in vivo clearance have been commonly observed among different
      datasets. The regression-based scaling factor for the in vitro-to-in vivo
      extrapolation has mitigated discrepancy between in vitro prediction and in vivo
      observation. In addition to the elimination by metabolic degradation, the
      important roles of transporter-mediated hepatic uptake and canalicular excretion
      have been increasingly recognized as a rate-determining step in the hepatic
      clearance. It has been, therefore, proposed that the in vitro assessment should
      allow the evaluation of clearances for both transporter(s)-mediated
      uptake/excretion and metabolic degradation. This review first outlines the
      limited ability of subcellular fractions such as liver microsomes to predict
      hepatic clearance in vivo. It highlights the advantages of cryopreserved human
      hepatocytes as one of the versatile in vitro systems for the prediction of in
      vivo metabolic clearance in human at the early development stage. The following
      section discusses the mechanisms underlying the systematic underprediction of in
      vivo intrinsic clearance by hepatocytes. It leads to the proposal for the
      assessment of hepatic uptake clearance as one of the kinetically important
      determinants for accurate predictions of hepatic clearance in human. The
      judicious combination of advanced technologies and understandings for the drug
      disposition allows us to rationally optimize new chemical entities to the drug
      candidate with higher probability of success during the clinical development.

PMID- 19408139
TI  - Adaptive computer control of anesthesia in humans.
AB  - This paper presents an efficient computer control technique for regulation of
      anesthesia in humans. The anesthetic used is propofol and the objective is to
      control the degree of hypnosis of the patient. The paper describes the basic
      hardware/software setup of the system and the closed-loop methodologies. The
      bispectral index (BIS) is considered as the feedback signal. The control methods
      proposed here are based in the use of proportional integral controllers with dead
      time compensation to avoid undesirable oscillations in the BIS signal during the
      process. The compensation is based on the Smith predictor. To guarantee the
      applicability of the method to different patients, an adaptive module to tune the
      compensator is developed. Some real and simulated results are presented in this
      work to attest the efficiency of the methods used.

PMID- 19408142
TI  - Isolation and synthesis of a new chromenochalcone and a new chromene from
      Orthosiphon glabratus.
AB  - Chemical investigation on Orthosiphon glabratus afforded 10 compounds, among
      which a chromenochalcone and a chromene are new. The structures of the new
      constituents were settled from their 1D- and 2D-NMR spectra. The synthesis of
      these two compounds and some of their analogues have been accomplished.

PMID- 19408141
TI  - Three new triterpenoid saponins from the leaves and stems of Panax quinquefolium.
AB  - Three new minor dammarane saponins, quinquenosides L10 (1), L14 (2), and L16 (3),
      were isolated from the leaves and stems of Panax quinquefolium L. By the
      combination of one- and two-dimensional NMR techniques and MS spectroscopic
      analysis, their structures were established as 20-O-(alpha-L-arabinopyranosyl-(1
      6)-O-beta-D-glucopyranosyl)-3-O-beta-D-glucopyranosyl-dammar-24-ene-3,12, 20
      triol (1), 20-O-alpha-L-arabinopyranosyl-3-O-(beta-D-glucopyranosyl-(1-2)-O-beta
      d-glucopyranosyl)-dammar-24-ene-3,12,20-triol (2), 3-O-(beta-D-glucopyranosyl-(1
      2)-O-beta-d-glucopyranosyl)-20-O-(beta-D-glucopyranosyl-(1-6)-beta-D
      glucopyranosyl)-dammarane-3,12,20,24,25-pentaol (3). The content of artemisinin
      was significantly enhanced by 3.0 mg l(- 1) of compounds 1, 2, and 3 in the
      callus of Artemisia annua.

PMID- 19408143
TI  - Rosenones A and B, new anthraquinone derivatives from Aitchisonia rosea.
AB  - Rosenones A (1) and B (2), new anthraquinone derivatives, have been isolated from
      the ethyl acetate soluble fraction of Aitchisonia rosea along with 1,3,6
      trihydroxy-2-methylanthraquinone (3) reported for the first time from this
      species.

PMID- 19408144
TI  - Two new steroidal saponins from the seeds of Allium cepa L.
AB  - Two new steroidal saponins, ceparosides C (1) and D (2), have been isolated from
      the seeds of Allium cepa L. Their structures have been established as 26-O-(beta
      D-glucopyranosyl)-(25R)-furost-5,20(22)-dien-3beta,26-diol-3-O-beta-D
      glucopyranosyl-(1 --> 4)-[alpha-l-rhamnopyranosyl (1 --> 2)]-beta-D
      galactopyranoside (1) and 26-O-(beta-D-glucopyranosyl)-(25S)-furost-5,20(22)-dien
      3beta, 26-diol-3-O-beta-D-glucopyranosyl-(1 --> 4)-[alpha-L-rhamnopyranosyl(1 -->
      2)]-beta-D-galactopyranoside (2) by means of spectral and chemical methods.

PMID- 19408145
TI  - Berbamine induces Fas-mediated apoptosis in human hepatocellular carcinoma HepG2
      cells and inhibits its tumor growth in nude mice.
AB  - Berbamine, a natural compound from the plant Berberis amurensis, is a traditional
      Chinese medicine mainly used in stimulating normal hematopoiesis in clinic. Our
      previous studies demonstrated that berbamine has anti-leukemia activity. In this
      study, we investigated the anticancer activity of berbamine against human
      hepatocellular carcinoma (HCC) HepG2 cells in vitro and in vivo. Berbamine
      treatment decreased the cell growth in a dose-dependent manner with an IC(50)
      value of 34.5 +/- 0.5 microM. Flow cytometric analysis of apoptosis using Annexin
      V/propidium iodide staining showed that the percentage of apoptotic cells was
      increased in a time-dependent manner. Berbamine treatment increased the
      expression level of Fas and P53, caused depolarization of mitochondrial membrane
      and decrease of membrane potential, and activated caspase-3, -8, and -9 in HepG2
      cells. Berbamine-induced apoptosis could be blocked by the broad caspase
      inhibitor z-VAD-fmk. HepG2 human HCC xenograft mice treated with berbamine showed
      a significant reduction in tumor growth rates compared to saline-treated mice.
      These studies suggest that berbamine exerts anticancer effects on human HCC HepG2
      cells in vivo and in vitro, the induction of p53 and the activity of the Fas
      apoptotic system may participate in the anticancer activity of berbamine in HepG2
      cells.

PMID- 19408146
TI  - Iridoid glucosides from leaves and stem barks of Parkia javanica.
AB  - Two new iridoid glucosides, javanicosides A (1) and B (2) along with the known
      compounds, ursolic acid and beta-sitosterol were isolated from the leaf and stem
      bark of Parkia javanica and the structures were established on the basis of
      detailed spectroscopic analysis (MS, 1D, and 2D NMR experiments). The new
      compounds were identified as 8-O-p-hydroxybenzoyl-6'-O-p-coumaroyl-mussaenosidic
      acid (1) and 7-O-E-3,4-dimethoxycinnamoyl-6'-O-beta-D-glucopyranosylloganic acid
      (2).

PMID- 19408147
TI  - Triterpenes from Astilbe chinensis.
AB  - Six new triterpenes, 3beta,6beta-dihydroxyurs-12-en-27-oic acid (1),
      3beta,6beta,24-trihydroxyurs-12-en-27-oic acid (2), 3beta,6beta,7alpha
      trihydroxyurs-12-en-27-oic acid (3), 3beta-acetoxy-6beta-hydroxyurs-12-en-27-oic
      acid (4), 3beta,6beta,24-trihydroxyolean-12-en-27-oic acid (5), and
      3beta,6beta,7alpha-trihydroxyolean-12-en-27-oic acid (6), were isolated from the
      rhizomes of Astilbe chinensis. Their structures were elucidated on the basis of
      1D- and 2D-NMR analyses and HR-MS experiments. The isolated compounds exhibited
      significant cytotoxic activities against the SK-N-SH and HL-60 cell lines.

PMID- 19408149
TI  - Two new cytotoxic acetogenins from Annona squamosa.
AB  - Two new annonaceous acetogenins named as squamostanin-A and squamostanin-B were
      isolated from 95% EtOH extract of the seeds of Annona squamosa. Their structures
      were determined by spectroscopic method, and their cytotoxicities were evaluated
      using MTT method.

PMID- 19408148
TI  - Phenolic compounds with cell protective activity from the fruits of Livistona
      chinensis.
AB  - Two new depsidones, livistones A (1) and B (2), and a new benzofurane, livistone
      C (3), together with the 11 known compounds including three stilbenes (4-6), four
      steroids, three flavan-3-ols, and an alkaloid were isolated from the fruits of
      Livistona chinensis. The structures of the new compounds were determined by
      spectroscopic methods. Compounds 1, 4-6 exhibited remarkable cell protective
      activities against H(2)O(2)-induced SH-SY5Y cell damage.

PMID- 19408150
TI  - Verticilliside, a new flavone C-glucoside from Enicostemma verticillatum.
AB  - Verticilliside (1), a new flavone C-glucoside, has been isolated from the ethyl
      acetate soluble fraction of Enicostemma verticillatum and its structure is
      assigned on the basis of the spectroscopic data. 5,7,4'-Trihydroxyflavone 8-C
      beta-D-glucopyranoside (2) and isoorientin 3'-O-methyl ether (3) have also been
      isolated for the first time from this species.

PMID- 19408151
TI  - Cytotoxic triterpene saponins from Alternanthera philoxeroides.
AB  - Four new pentacyclic triterpene saponins, philoxeroidesides A-D (1-4) were
      isolated from the aerial parts of Alternanthera philoxeroides. Their structures
      were elucidated on the basis of 1D- and 2D-NMR experiments and MS analyses.
      Philoxeroidesides A-D (1-4) showed cytotoxic activities against SK-N-SH and HL60
      cell lines.

PMID- 19408152
TI  - Three new Diels-Alder type adducts from the stem bark of Morus cathayana.
AB  - Three new Diels-Alder type adducts cathayanons C (1), D (2), and E (3), together
      with one known compound sanggenon C (4), were isolated from the stem bark of
      Morus cathayana. Their structures were fully elucidated by spectroscopic and
      chemical methods. Compound 2 showed good anti-oxidation activity with the
      inhibitory rate of malondialdehyde being 88% at a concentration of 10(- 6) mol/l.

PMID- 19408153
TI  - Total synthesis of (+)-conagenin.
AB  - A new approach for the synthesis of the (+)-conagenin has been achieved based on
      Evans asymmetry syn-aldol reaction and the self-regeneration of stereocenters
      strategy.

PMID- 19408154
TI  - Total synthesis of (-)-talaumidin and (-)-galbelgin.
AB  - ( - )-Talaumidin (1) and ( - )-galbelgin (2) have been synthesized via 4
      pentenoic acid as a starting material with the overall yield of about 17.8 and
      16.9%, respectively. The key steps include Evans asymmetry anti-aldol reaction,
      TBS protection, hydroboration, oxidation, Friedel-Crafts arylation, etc.

PMID- 19408156
TI  - Effects of gender and personality on the Conners Continuous Performance Test.
AB  - A total of 91 university community participants were evaluated on the five
      personality factors (NEO-Five Factor Inventory; NEO-FFI) and with the Conners
      Continuous Performance Test (CPT). Gender differences for the Conners CPT
      variables were found such that the men were faster and less variable in their
      reaction times than the women, and the women were more sensitive in terms of
      signal detection and conservative in their responses than the men, consistent
      with the data reported by Conners, Epstein, Angold, and Klaric (2003) for a
      normative sample of 9-18 year olds. Interesting relationships between personality
      factors and the CPT variables were seen for the male and female groups,
      especially in terms of response style and vigilance. For the combined genders,
      higher vigilance was associated with higher neuroticism, lower extraversion, and
      lower agreeableness. Lower conscientiousness was associated with a more risk
      taking/less conservative response bias. The men were more vigilant than the
      women, and for the men, this higher vigilance was related to lower
      conscientiousness, with trends for relationships with greater neuroticism and
      lower agreeableness. In the women, higher vigilance was related to lower
      extraversion, consistent with other studies. Men who were more extraverted also
      tended to be less conservative/more risk taking in their response style. A more
      risk-taking response style in women was associated with higher neuroticism,
      higher openness, and lower conscientiousness. The findings are interpreted in
      terms of underlying biological bases of behavior.

PMID- 19408159
TI  - Different laterality patterns of the error-related negativity in corrected and
      uncorrected errors.
AB  - While measuring event-related brain potentials, a divided visual field paradigm
      was used to discern laterality patterns of the error-related negativity (ERN) in
      healthy human participants. Two tasks of hemispheric specialty were used
      (bargraph judgement, lexical decision) and a flanker task. For corrected errors
      in all tasks, stronger ERN amplitude was found following right visual field
      presentation. For corrected errors in the specialised tasks, shorter ERN latency
      was revealed on the side to which the stimulus was presented, while for
      uncorrected errors it was shorter on the other side. In the flanker task, ERN
      latency after corrected errors was shorter over the RH regardless of the side to
      which the stimulus was presented. Results are interpreted to reveal patterns of
      hemispheric specialisation, independence, and cooperation in error detection that
      depend on the type of error been committed.

PMID- 19408160
TI  - Annual disease burden due to human papillomavirus (HPV) 6 and 11 infections in
      Finland.
AB  - In addition to cancer of the lower female genital tract, human papillomaviruses
      (HPV) are associated with a large number of benign, precancer and cancer lesions
      at different anatomic sites in both genders. Malignant tumours and their
      precursors are usually attributed to the oncogenic (high-risk, HR) HPV types,
      whereas benign lesions (papillomas) are associated with the low-risk (LR) HPV
      types, most notably with HPV6 and HPV11. Until recently, the main interest in HPV
      research has been focused on HR-HPV types and their associated pathology, and
      much less attention has been paid to the lesions caused by the LR-HPV types. With
      the recent licensing of an effective prophylactic vaccine against the 2 most
      important LR-HPV types (HPV6 and HPV11), it has become timely to make a
      systematic survey on the annual disease burden due to these 2 HPV genotypes in
      our country. These types of data should form the foundation for all calculations
      of the annual costs needed to treat these diseases by conventional means.
      Accurate estimates of disease burden are also mandatory for all modelling of the
      cost-effectiveness of prophylactic HPV6 and HPV11 vaccines. If proven useful for
      any of these purposes, this document will have fulfilled its purpose. In the
      first step, published HPV literature was used to create a list of benign,
      premalignant and malignant lesions associated with this virus at different
      anatomic sites. GLOBOCAN 2004 (IARC) database was used to derive the global
      numbers of incident cases for each of these malignancies in 2002, and the Finnish
      Cancer Registry (FCR) website for obtaining these (y 2005) numbers in Finland.
      The evidence linking HPV to each individual tumour category was classified as: 1)
      established, 2) emerging, and 3) controversial. All published evidence was
      weighted for each individual malignant, premalignant and benign lesion, anatomic
      region by region, while assessing the attributable fraction of HPV6/11 genotypes
      in each lesion. Because benign and most of the precancer lesions are not
      registered by FCR or GLOBOCAN, different approaches had to be used to derive the
      best estimates for their incidence, based on published literature or other
      registries (e.g. genital wart registry of the UK and Wales, and mass screening
      registry of FCR). With a lack of reasonable consensus, a lower and an upper limit
      was set for the range of estimates. In cases with different age-specific
      incidence (e.g. genital warts), the population pyramid of Finland was used to
      calculate the incident cases. Where well established, the different incidence
      rates among males and females were used to calculate the numbers of incident
      cases by gender. The malignant neoplasms with established or emerging evidence on
      the causal role of HPV are listed by their ICD-10 codes in Table I. Included in
      this list are also 2 controversial malignancies (colorectal cancer and
      endometrial cancer), of which the contradictory HPV data are critically
      discussed. The third major cancer in this same category (prostate cancer) was not
      included in the list, because the data are clearly insufficient to categorize
      this entity even among the emerging HPV associated malignancies. Estimated
      disease burden due to HPV6/11 in Finland, calculated as numbers of annual new
      cases by anatomic region and tumour type is given in Table II, and summarized in
      Figure 1. The present analysis implicates that a minimum of 12,666 to 13,066 new
      cases of HPV6- or HPV11-associated clinical lesions would be detected each y in
      Finland, if all were registered. Notably, these numbers represent the disease
      burden due to these 2 HPV types. However, these clinical lesions only represent a
      small minority of the total viral burden due to the infections by these 2 HPV
      genotypes. This is because the vast majority of all infections by these
      ubiquitous viruses are latent, being transient in nature and spontaneously
      resolving within a few months (up to 1 y), without ever developing a clinically
      detectable disease. This spontaneous clearance does not make these latent
      infections less important, however, because as long as the virus reservoir
      exists, it serves as the source of viral transmission to susceptible individuals,
      with a multitude of HPV6/11 associated pathologies as a potential outcome, as
      described in this document. The implications of these data in the era of
      effective prophylactic HPV vaccination against HPV6 and HPV11 should be clear.

PMID- 19408161
TI  - The future role of general practice: managing multiple agendas.

PMID- 19408162
TI  - The use of Glasgow Coma Scale in injury assessment: a critical review.
AB  - PRIMARY OBJECTIVE: Patients with brain injuries are assessed using the Glasgow
      Coma Scale (GCS). This review evaluates the use of GCS scoring in medical
      literature and identifies the reasons for inaccuracy. LITERATURE SELECTION AND
      CRITICAL APPRAISAL: Pubmed and ISI Web of Knowledge SM were searched using
      specific keywords. The authors critically appraised the current state of GCS
      scoring, GCS definitions, the time and frequency of assessment, confounders, GCS
      reporting and GCS assessment schemes. MAIN OUTCOME AND RESULTS: More than 90% of
      the publications using GCS scoring cite the 14-item GCS rather than the 15-item
      GCS. The timing of the initial GCS assessment is inconstant. GCS components are
      seldom utilized, contributing to the loss of information. Confounders are often
      not reported and, if they are, not in a standardized manner. The order of the GCS
      components is not consistent. CONCLUSIONS: The current inconsistent and
      inappropriate use of GCS diminishes its reliability in both a clinical and a
      scientific context. A consensus statement is needed to correct this situation.
      Citing the correct references, early and repeated GCS assessments at defined
      intervals, standardized reporting of confounders and GCS component plus sum
      scores, and the utilization of a uniform assessment scheme are recommended.

PMID- 19408163
TI  - Prognostic factors of return to work after acquired brain injury: a systematic
      review.
AB  - PRIMARY OBJECTIVE: To provide insight into the prognostic and non-prognostic
      factors of return to work (RTW) in people with traumatic and non-traumatic
      acquired brain injury (ABI) who were working before injury. METHODS: A systematic
      literature search (1992-2008) was performed, including terms for ABI, RTW and
      prognostic factors. The methodological quality of the studies was determined.
      Evidence was classified as strong (positive, negative or no), weak or
      inconsistent. MAIN OUTCOMES AND RESULTS: Following classification of the studies,
      22 studies were included. Strong evidence was found that 'gender' and 'anatomic
      location' were not associated with RTW after non-traumatic ABI and that both
      'injury severity' (classified by the Glascow Coma Scale) and 'suffering from
      depression' or 'anxiety' were not associated with RTW after traumatic ABI. In
      addition strong evidence was found for the negative prognostic value on RTW of
      the 'inpatient length of stay', after traumatic ABI. Weak evidence was found for
      the three trainable/treatable factors 'ability to perform activities of daily
      living', 'residual physical deficits/higher disability level' and 'number of
      associated injuries'. CONCLUSION: Strong evidence was found that six variables
      either had no association or a negative association with RTW. It is recommended
      to focus in rehabilitation on the factors for which weak evidence was found but
      that are trainable/treatable with the goal of improving the process of vocational
      rehabilitation.

PMID- 19408164
TI  - Association of injury severity, MRI-results and ApoE genotype with 1-year outcome
      in mainly mild TBI: a preliminary study.
AB  - PRIMARY OBJECTIVE: To study the ability of MRI findings, apolipoprotein E (ApoE)
      genotype, the Glasgow Coma Score (GCS) and duration of post-traumatic amnesia
      (PTA) to predict the 1-year outcome in traumatic brain injury (TBI). RESEARCH
      DESIGN: A prospective study in unselected emergency room patients with an acute
      TBI, followed for 1 year. METHODS AND PROCEDURES: Thirty-three consecutive
      patients were studied. The TBI severity was assessed with GCS and duration of
      PTA. Brain MRI scans were obtained within approximately 1 week post-injury. The
      ApoE genotypes were determined by standard methods. The outcome was evaluated
      with the Head Injury Symptom Checklist and the Glasgow Outcome Scale (extended) 1
      year after the injury. The prognostic value of the explanatory variables was
      evaluated with multiple linear regression analysis. MAIN OUTCOMES AND RESULTS:
      The presence of traumatic axonal injury lesions or contusions in MRI and duration
      of PTA were independent predictors of poor outcome. The ApoE genotype and GCS
      were not associated with outcome. CONCLUSIONS: In multivariate models, the
      duration of PTA and acute MRI are the best predictors of 1-year outcome in TBI,
      whereas the prognostic values of GCS and ApoE are modest. The dominating role of
      GCS in assessing TBI severity should be questioned.

PMID- 19408165
TI  - The neural correlates of cognitive fatigue in traumatic brain injury using
      functional MRI.
AB  - PRIMARY OBJECTIVE: The present study used fMRI (functional magnetic resonance
      imaging) to objectively assess cognitive fatigue in persons with traumatic brain
      injury (TBI). It was hypothesized that while performing a cognitive task, TBI
      participants would show increased brain activity over time, indicative of
      increased cerebral 'effort' which might manifest as the subjective feeling of
      cognitive fatigue. METHODS AND PROCEDURES: Functional MRI was used to track brain
      activity across time while 11 TBI patients with moderate-severe injury and 11 age
      matched healthy controls (HCs) performed a modified Symbol Digit Modalities Task
      (mSDMT). Cognitive fatigue was operationally defined as a relative increase in
      cerebral activation across time compared to that seen in HCs. ROIs were derived
      from the Chauduri and Behan model of cognitive fatigue. MAIN OUTCOMES AND
      RESULTS: While performing the mSDMT, participants with a TBI showed increased
      activity, while HCs subsequently showed decreased activity in several regions
      including the middle frontal gyrus, superior parietal cortex, basal ganglia and
      anterior cingulate. CONCLUSIONS: Increased brain activity exhibited by
      participants with a TBI might represent increased cerebral effort which may be
      manifested as cognitive fatigue. Functional MRI appears to be a potentially
      useful tool for understanding the neural mechanisms associated with cognitive
      fatigue in TBI.

PMID- 19408166
TI  - Post-traumatic mutism in children.
AB  - OBJECTIVE: To explore the pathological mechanism of post-traumatic mutism (PTM)
      in children. METHODS: A retrospective study of 16 children who suffered from
      severe head injury and developed PTM. RESULTS: Post-traumatic coma lasted from 2
      72 days, average 15.5 days; while post-traumatic mutism lasted from 2-56 days,
      average 11.94 days. The correlation between duration of coma and mutism was
      significant (p < 0.001). SPECT found that multiple persistent ischaemic brain
      regions occurred in all patients; the mean number of regions was 5.6. The
      patients were sub-divided into three groups based on the number of ischaemic
      regions: group 1, < or = 4; group 2, 5 approximately 6; group 3, > or = 7. The
      duration of mutism did not differ significantly between groups 1 and 2, but the
      difference between group 3 and the other two groups combined was significant (p <
      0.05). CONCLUSION: Most PTM occurred in patients with diffuse brain injury. The
      duration of mutism was related to the number of ischaemic brain regions and the
      duration of post-traumatic coma.

PMID- 19408167
TI  - The dynamic detection of NO during stroke and reperfusion in vivo.
AB  - PURPOSE: Nitric oxide (NO) has been implicated as a mediator of synaptic
      transmission and a pathological factor in stroke/reperfusion. The purpose of this
      study was to detect the change of NO concentration in rat hippocampus during
      global cerebral ischemia and reperfusion in vivo and to reveal effects of
      different NO synthases (NOS). METHOD: In the present study, the real-time record
      of NO levels in rat hippocampus was obtained by using a NO sensor during the
      global cerebral ischemia and the initial stage of reperfusion. The effects of two
      inhibitors of NOS on NO concentration were also observed. The two inhibitors were
      respectively administrated intravenously at the onset of reperfusion and 1 hour
      later. RESULTS: The change of the NO concentration in the initial stage of
      reperfusion was 0.768 +/- 0.029 microM. 7-nitroindazole (7-NI, inhibitor of nNOS)
      had a strong inhibitive effect on NO synthesis at both time points, while 1400W
      dihydrochloride (1400W, inhibitor of iNOS) had no significant effect on the NO
      synthesis. CONCLUSIONS: The in vivo detection revealed the real dynamic change of
      NO concentration, which is much more reliable than the in vitro method. The
      results showed that, during the initial stage of reperfusion, NO biosynthesis was
      mainly in an nNOS-dependent manner. Thus, the toxicity of NO in this process had
      a close relationship with the activity of nNOS but not iNOS.

PMID- 19408168
TI  - The protective effect of the ketogenic diet on traumatic brain injury-induced
      cell death in juvenile rats.
AB  - BACKGROUND: The ketogenic diet (the KD) is an effective treatment for intractable
      epilepsy, especially in the paediatric population, and a growing number of
      studies have shown the neuroprotective role of the KD. However, few studies
      focused on the neuroprotective effects of the KD in traumatic brain injury (TBI).
      The present study aimed to investigate the effects of the KD on TBI. METHODS AND
      PROCEDURES: Male Sprague-Dawley rats (n = 60) were randomly divided into four
      groups according to the diet fed (the KD vs normal diet) and whether brain was
      injured or not. TBI was produced using Feeney weight drop model. Brain oedema was
      estimated by wet/dry weight ratio; Bax and Bcl-2 mRNA levels were determined by
      RealTime-PCR; Bax and Bcl-2 protein levels were detected by Western blot.
      Furthermore, cellular apoptosis in the penumbra area was examined using terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method.
      MAIN OUTCOMES AND RESULTS: The results indicated that both Bax mRNA and protein
      levels were significantly elevated 72 hours after TBI and decreased by KD
      administration. Neither TBI nor the KD affected Bcl-2 mRNA and protein levels. KD
      administration also reduced brain oedema and cellular apoptosis. CONCLUSION:
      These results suggest that the KD might be a useful treatment for children
      suffering from the consequences of TBI.

PMID- 19408169
TI  - Reversible post-traumatic bilateral extensive restricted diffusion of the brain.
      A case study and review of the literature.
AB  - PRIMARY OBJECTIVE: To increase the knowledge about diffuse traumatic brain injury
      (TBI) by reporting the magnetic resonance imaging (MRI) findings observed in a
      patient with reversible extensive restricted diffusion of the brain at diffusion
      weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. CASE STUDY:
      An 18-year-old patient was admitted after high-energy closed TBI. Glasgow Coma
      Scale score was 4. Head computed tomography showed small left frontal and
      temporal haemorrhagic contusions and a small haemorrhage in the left thalamus.
      Ten days later, brain MRI showed diffuse high-signal intensity on T2-weighted
      images and DWI and restricted diffusion in the subcortical white matter of both
      centri semiovali, genu and splenium of corpus callosum and parietal cortex
      bilaterally (mean ADC value = 0.434-0.811 x 10(-3) mm(2) s(-1)). Eleven days
      later, follow-up brain MRI showed gliotic changes in the left splenium of corpus
      callosum, a clearcut decrease of T2-weighted high-signal intensity and resolution
      of abnormalities at DWI and ADC maps in all other involved sites. This was
      confirmed 36 days later. Three months later, the patient did not show
      neurological, cognitive or neuropsychiatric deficits. CONCLUSIONS: In the patient
      reported herein, closed TBI most likely induced diffuse excitotoxic injury of the
      brain which resulted in mainly reversible cytotoxic or intramyelinic oedema.

PMID- 19408170
TI  - Treatment of hirsutism.

PMID- 19408171
TI  - Phenotypic and pharmacogenetic aspects of ovulation induction in WHO II
      anovulatory women.
AB  - Because of an enormous increase in pharmacogenetic and -genomic knowledge, an era
      of predicting drug response on the basis of one's genome is drawing close to
      reality. Anovulation is the most common cause of infertility, and outcomes of
      treatment are often unpredictable. This review aims to summarise in what way
      genetic variability might modify effects of drug-metabolising enzymes,
      transporters and receptors, thereby altering response to drugs used in ovulation
      induction.

PMID- 19408173
TI  - Plasma visfatin level in lean women with PCOS: relation to proinflammatory
      markers and insulin resistance.
AB  - OBJECTIVES: The present study was undertaken to investigate the association
      between plasma visfatin concentrations and inflammatory markers such as
      interleukin-6 (IL-6) and high-sensitive C-reactive protein (hsCRP) in company
      with several metabolic parameters in lean women with polycystic ovary syndrome
      (PCOS). METHODS: The study group consisted of 21 lean women with PCOS (BMI 20.74
      +/- 1.74 kg/m(2)) and 15 healthy, normally menstruating women (BMI 20.85 +/- 2.08
      kg/m(2) control group). PCOS was defined according to the Rotterdam criteria.
      Visfatin, IL-6, hsCRP, hyperandrogenism markers and metabolic markers were
      examined in all PCOS and control women. RESULTS: Plasma visfatin level in the
      PCOS group was higher than that in the control group. Plasma hsCRP and IL-6
      levels in PCOS group were similar with the control group. Plasma visfatin levels
      were positively associated with total cholesterol, high density lipoprotein,
      hirsutism score, total testosterone and FAI. Plasma visfatin level was negatively
      associated with SHBG. However, there were no correlation between plasma visfatin
      level and IL-6 and hsCRP. In multivariate regression analyses, only FAI and high
      density lipoprotein-cholesterol (HDL-C) showed a significant association with
      serum visfatin. CONCLUSION: Our data indicates that plasma visfatin levels are
      associated with HDL-C and markers of hyperandrogenism, but it is not associated
      with proinflammatory markers and insulin resistance in lean women with PCOS.

PMID- 19408172
TI  - Effect of a 2-month treatment with Klamin, a Klamath algae extract, on the
      general well-being, antioxidant profile and oxidative status of postmenopausal
      women.
AB  - BACKGROUND AND AIM: Because of a growing demand for alternative treatments of the
      psychological and somatic/vasomotor symptoms related to menopausal transition, in
      this study we aimed to investigate the effect of a 2-month supplementation period
      with the Klamath algae extract (Klamin, Nutratec Srl, Urbino, Italy) on the
      general and psychological well-being of a group of 21 menopausal women not
      treated with hormonal therapy, as well as on their oxidative stress status and
      level of antioxidants. Klamin is an extract naturally rich in powerful algal
      antioxidant molecules (AFA-phycocyanins) and concentrated with Klamath algae's
      natural neuromodulators (phenylethylamine as well as natural selective MAO-B
      inhibitors). CONCLUSIONS: At the end of the Klamin supplementation period, plasma
      lipid peroxidation significantly decreased (as proven by a significant lowering
      of plasma MDA levels), while the overall antioxidant system improved thanks to
      the significant increase in the plasma levels of carotenoids, tocopherols and
      retinol. Furthermore, the average Green Scale score, which evaluates menopausal
      symptoms and thus by contrast the overall and psychological well-being of
      menopausal women, was significantly reduced. As it did not show the steroid-like
      effects on the hormonal parameters, Klamin could be proposed both as a valid
      natural remedy for women seeking an alternative to hormonal therapy, as well as
      as a complementary treatment for many climacteric symptoms.

PMID- 19408175
TI  - High resistin and interleukin-6 levels are associated with gestational diabetes
      mellitus.
AB  - Resistin is a cysteine-rich adipokine originally described as a molecular link
      between obesity and insulin resistance in rodents. In this study, we hypothesised
      that serum resistin concentrations are elevated in patients with gestational
      diabetes mellitus (GDM) when compared with pregnant women with normal glucose
      tolerance (NGT) and related to proinflammatory interleukin-6 (IL-6) and other
      factors conferring insulin resistance. Serum resistin and IL-6 were measured by
      enzyme-linked immunosorbent assay (ELISA) in 81 women with GDM, 82 women with NGT
      between 24 and 31 weeks of gestation and 25 healthy non-pregnant women. Resistin
      concentrations were significantly higher in the GDM (21.9 [17.55-25.40] ng/ml)
      than in the NGT group (19.03 [15.92-23.91] ng/ml, p = 0.047), as well as in the
      non-pregnant women (14.8 [13.7-16.6] ng/ml, p < 0.0001). Serum IL-6 levels were
      elevated in the GDM (1.0 [0.7-1.5] pg/ml) as compared with the NGT group (0.8
      [0.5-1.1] pg/ml, p = 0.006) and the non-pregnant controls (0.7 [0.5-1.1] pg/ml, p
      = 0.04). Multiple regression analysis revealed that in the pregnant women
      circulating resistin was related to serum IL-6 (beta = 0.33, p = 0.0004) but not
      to insulin or the index of insulin resistance. It is concluded that the finding
      of high resistin and IL-6 levels in women with gestational diabetes might confirm
      a role of low-grade inflammation in the pathogenesis of GDM.

PMID- 19408174
TI  - Serum resistin and adiponectin levels in women with polycystic ovary syndrome.
AB  - AIM: This study was performed to compare the serum levels of resistin and
      adiponectin in women with polycystic ovary syndrome (PCOS) and normal controls.
      MATERIALS AND METHODS: Seventy-six patients (36 obese, 40 non-obese) with PCOS
      and 42 healthy subjects were included in the study. Serum levels of resistin,
      adiponectin, follicle-stimulating hormone, luteinising hormone,
      dehydroepiandrosterone sulfate (DHEA-S), 17-hydroxy progesterone, free
      testosterone, androstenedione, glucose, insulin and lipid parameters were
      measured. Insulin resistance and carbohydrate metabolism were evaluated by using
      the homeostasis model (HOMA) and the area under the insulin curve (AUCI).
      RESULTS: Plasma resistin levels, HOMA-IR and AUCI were significantly higher and
      adiponectin level was lower in women with PCOS than those in healthy women.
      Plasma resistin levels were similar among obese and non-obese women with PCOS. No
      correlation was observed between resistin, body mass index (BMI), HOMA-IR, AUCI,
      insulin, lipid parameters and serum androgen levels. In obese PCOS patients,
      adiponectin levels were lower than in the lean PCOS patients. A negative
      correlation was observed among adiponectin, HOMA-IR, AUCI, BMI, testosterone,
      DHEAS, total-cholesterol, LDL-cholesterol and lipoprotein (a) levels. CONCLUSION:
      These results suggest that the serum adiponectin level may be involved in the
      pathogenesis of PCOS. But resistin levels were independently associated with
      insulin resistance and BMI in PCOS patients. Nevertheless, wider-scale trials are
      required to be performed on this subject.

PMID- 19408176
TI  - An open-label study of subdermal implants of estradiol-only versus subdermal
      implants of estradiol plus nomegestrol acetate: effects on symptom control, lipid
      profile and tolerability.
AB  - OBJECTIVE: To compare the effects of continuous 17-beta estradiol-only silastic
      implants with those of continuous 17-beta estradiol plus continuous nomegestrol
      acetate silastic implants on symptom control, lipid profile and tolerability in
      postmenopausal women. METHODS: This was an open-label, parallel-group study.
      Women with and without uterus and no contraindications to hormone therapy (HT) in
      this study, we consider as HT the replacement of Estrogens-only and Estrogens +
      Progestogens Therapy, were enrolled. Each subject was assigned to receive four 17
      beta estradiol-only silastic implants (women without uterus), or four 17-beta
      estradiol plus one nomegestrol acetate silastic implant (women with intact
      uterus), for 1 year. RESULTS: A total of 40 subjects were enrolled and received,
      the silastic implants of which 40 (100.0%) subjects completed the study (n = 20,
      estradiol only; n = 20, estradiol plus nomegestrol acetate). The incidence of
      postmenopausal symptoms decreased significantly. No significant decreases in
      total cholesterol (1.3%), low-density lipoprotein cholesterol (1.1%),
      triglycerides (1.2%) and fasting glucose ((1.3%) serum levels were observed in
      both groups, whereas high-density lipoprotein (HDL) cholesterol increased
      significantly (2.8%), during the study in both groups. The incidences of adverse
      events were similar in both treatment groups. CONCLUSIONS: Women treated with 17
      beta estradiol-only silastic implants or 17-beta estradiol plus nomegestrol
      acetate silastic implants showed significant improvement of postmenopausal
      symptoms, including urogenital and sexual health symptoms and a significant
      increase in HDL cholesterol and no significant differences in other lipid
      profiles and tolerability.

PMID- 19408177
TI  - Who is making lifestyle changes due to preventive health care information? A
      demographic analysis.
AB  - This paper sought to describe from a set of demographic and lifestyle
      characteristics, the person who is significantly and positively impacted by
      preventive health care (PHC) information. Based on past research, six two-part
      hypotheses (PHC information and lifestyle) were developed, with a total
      examination of 12 possible relationships. Five of the six hypotheses were at
      least partially accepted, as were eight out of the 12 possible relationships. In
      addition, there was at least one significant relationship with a demographic
      variable in 12 of the 13 lifestyle change variables. It can be said with
      confidence that persons who are seeking and are positively impacted by PHC
      information are better educated, have higher incomes, are female, usually older,
      and married. The most important lifestyle changes emanating from PHC information
      are "changes in eating habits," "having periodic physician checkups," "utilizing
      nutritional labeling," and "joining a health club or wellness center." "Changes
      in social life," "sleeping habits," "getting regular exercise," and "attendance
      at health fairs and seminars" were also associated with the utilization of PHC
      information, but to a lesser extent.

PMID- 19408179
TI  - Characteristics of physicians targeted by the pharmaceutical industry to
      participate in e-detailing.
AB  - Electronic detailing (e-detailing) has been introduced in the last few years by
      the pharmaceutical industry as a new communication channel through which to
      promote pharmaceutical products to physicians. E-detailing involves using digital
      technology, such as Internet, video conferencing, and interactive voice response,
      by which drug companies target their marketing efforts toward specific physicians
      with pinpoint accuracy. A mail survey of 671 Iowa physicians was used to gather
      information about the physician characteristics and practice setting
      characteristics of those who are usually targeted by pharmaceutical companies to
      participate in e-detailing. A model is developed and tested to explain firms'
      targeting strategy for targeting physicians for e-detailing.

PMID- 19408178
TI  - Marketing defibrillation training programs and bystander intervention support.
AB  - This exploratory study identifies perceptions of and participation in
      resuscitation training programs, and bystanders' willingness to resuscitate
      cardiac arrest victims. While most of the study's participants greatly appreciate
      the importance of saving someone's life, many indicated that they did not feel
      comfortable assuming this role. The findings also demonstrate there is a
      relationship between type of victim and bystanders' willingness to intervene.
      Yet, bystander intervention discomfort can be overcome with cardiopulmonary
      resuscitation and defibrillation training, particularly when the victim is a
      coworker or stranger. Further implications of these findings are discussed and
      modifications to public access defibrillation (PAD) training programs' strategy
      and communications are proposed.

PMID- 19408181
TI  - Factors influencing healthy eating habits among college students: an application
      of the health belief model.
AB  - Poor eating habits are an important public health issue that has large health and
      economic implications. Many food preferences are established early, but because
      people make more and more independent eating decisions as they move through
      adolescence, the transition to independent living during the university days is
      an important event. To study the phenomenon of food selection, the heath belief
      model was applied to predict the likelihood of healthy eating among university
      students. Structural equation modeling was used to investigate the validity of
      the health belief model (HBM) among 194 students, followed by gender-based
      analyses. The data strongly supported the HBM. Social change campaign
      implications are discussed.

PMID- 19408180
TI  - Marketing and reputation aspects of neonatal safeguards and hospital-security
      systems.
AB  - Technological advancements have migrated from personal-use electronics into the
      healthcare setting for security enhancements. Within maternity wards and
      nurseries, technology was seen as one of best way to protect newborns from
      abduction. The present study is a focus on what systems and methods are used in
      neonatal security, the security arrangements, staff training, and impacts outside
      the control of the hospital, customer satisfaction and customer relations
      management. Through hypothesis-testing and exploratory analysis, gender biases
      and extremely high levels of security were found within a web-enabled and
      professional sample of 200 respondents. The factor-based constructs were found to
      be, in order of the greatest explained variance: security concerns, personal
      technology usage, work technology applications, and demographic maturity
      concerns, resulting in four factor-based scores with significant combined
      variance of 61.5%. It was found that through a better understanding on the
      importance and vital need for hospitals to continue to improve on their
      technology-based security policies significantly enhanced their reputation in the
      highly competitive local healthcare industry.

PMID- 19408182
TI  - Clinical and histopathological results following TriPollar radiofrequency skin
      treatments.
AB  - INTRODUCTION: Skin laxity, wrinkles and cellulite are common aesthetic problems
      associated with the aging process. These symptoms are due to the weakening and
      thinning of dermal connective tissue and the enlargement of hypodermal fat cells.
      The aim of this study was to evaluate the safety and efficacy of the TriPollar RF
      technology in reducing fat and collagen regeneration. METHODS: Twelve healthy
      patients underwent weekly treatments on different body sites using the TriPollar
      technology. Treatment areas were photographed and measured and patient
      satisfaction was monitored. One abdominal patient consented to a series of
      TriPollar treatments prior to her scheduled abdominoplasty. A controlled
      histopathology analysis was performed on skin samples taken during the
      abdominoplasty procedure. RESULTS: Histopathological examination revealed marked
      differences between treated and non-treated abdominal skin areas. An increase of
      49% in dermal thickness, focal thickening of collagen fibers and focal shrinkage
      of fat cells was shown following TriPollar treatments. Average patient
      satisfaction indicated clear satisfaction with the clinical results achieved.
      CONCLUSION: The TriPollar is a safe and effective non-invasive technology leading
      to skin tightening and body shaping. Histology results indicate changes at the
      dermal and fat layers following TriPollar treatments resulting in increased
      collagen regeneration and stimulated fat metabolism.

PMID- 19408183
TI  - Sibling agreement on retrospective reports of parental alcoholism and other
      childhood events.
AB  - Studies have used siblings to verify subject reports of retrospective data and
      examined variables influencing subject-sibling agreement, but questions remain.
      From 1998 to 2000, we examined a community sample of women (N = 143) in a
      metropolitan area, aged 21-60, balanced by race, parental alcoholism, and social
      class, as well as their siblings, using standardized, self-administered
      questionnaires and an interview. RESEARCH QUESTIONS: Do subject and sibling
      reports agree? Do reports vary by subject characteristics, or the type of
      childhood experience? Descriptive statistics showed that agreement was strong for
      measures of parental alcoholism and psychiatric problems, weaker for family
      environment, and varied little by subject characteristics. Study limitations and
      implications are noted, and future research suggested.

PMID- 19408184
TI  - A real-life, ecologically valid test of executive functioning: the executive
      secretarial task.
AB  - A major goal of neuropsychological assessment is predicting a person's level of
      functioning in daily life. Making predictions about everyday executive
      functioning based on tests is problematic because of the contrast between demands
      made in the test environment and demands made in everyday life (Shallice &
      Burgess, 1991). As executive functions play an important role in independent
      functioning, tests with robust psychometric properties and ecologically validity
      are needed. We developed the Executive Secretarial Task (EST) and assessed 92
      participants: 35 brain-injured patients and 57 controls. Analyses showed the EST
      is sensitive to executive problems and has concurrent and ecological validity.

PMID- 19408185
TI  - Diagnostic evaluation of platelet disorders: the past, the present, and the
      future.

PMID- 19408186
TI  - Diagnostic assessment of platelet disorders: what are the challenges to
      standardization?
AB  - The platelet disorders are a group of heterogeneous, congenital and acquired
      bleeding disorders associated with impaired platelet function. There is a growing
      interest in standardizing the assessment of these disorders, but this is
      challenged by their heterogeneity, the absence of widely accepted diagnostic
      criteria, and inconsistency in laboratory testing practices for platelet
      disorders. Symptoms commonly associated with platelet disorders include rapid
      onset bleeding with hemostatic challenges, peripartum bleeding, menorrhagia,
      epistaxis, gingival bleeding, and increased bruising. Attempts have been made to
      standardize the assessment of these symptoms, using clinical tools and bleeding
      scores. However, there are currently no standardized tools available with proven
      utility for the assessment of platelet disorders, apart from a tool specifically
      designed to assess Quebec platelet disorder. There have been several efforts to
      improve and standardize the laboratory assessment of platelet disorders. These
      efforts include guidelines from the International Society on Thrombosis and
      Haemostasis and the Clinical and Laboratory Standards Institute. Recent research
      indicates that the application of standardized laboratory tests for the
      assessment of platelet disorders in individuals referred for bleeding problems
      has valuable diagnostic utility. This has provided further incentive to
      standardize clinical and laboratory approaches to improve the diagnostic
      evaluation of platelet disorders worldwide.

PMID- 19408187
TI  - Internal quality control and external quality assurance of platelet function
      tests.
AB  - Internal quality control (IQC) and external quality assurance (EQA) are distinct
      processes that contribute to ensure the overall quality (i.e., correctness) of
      laboratory test procedures. This review summarizes the current position of IQC
      and EQA in platelet function testing. These processes are in their infancy for
      these tests, despite the many years in which these tests have been performed
      within diagnostic hemostasis laboratories. This is understandable, due to the
      many challenges imposed by the requirements of the tests themselves and of the
      IQC and EQA processes, namely the regular availability, and ongoing supply and
      transport, of fresh blood containing functional platelets for testing within a
      very short time frame. Nevertheless, recently published studies have shown that
      IQC and EQA are both feasible for platelet function testing, although these
      processes have typically been undertaken in some modified form compared with
      other tests of hemostasis. Several EQA organizations are currently involved in
      providing support to laboratories that perform platelet function testing.
      Initiatives to date include cross-laboratory challenges for PFA-100 testing,
      several patterns of practice surveys, and several other EQA challenges related to
      dense granules and light transmission aggregometry. EQA organizations may be best
      placed to act as facilitators to the process of improving diagnostic testing for
      platelet function, which supplements the role of expert organizations.

PMID- 19408188
TI  - Screening tests of platelet function: update on their appropriate uses for
      diagnostic testing.
AB  - Global tests of platelet function are often used as screening tests during the
      laboratory investigation of individuals with suspected hemostatic defects.
      Because global tests of platelet function do not enable specific diagnosis of
      platelet disorders, they are normally performed as the first part of a two-step
      strategy that requires further testing with more specialized assays of platelet
      function to confirm or refute the diagnosis. The most commonly proposed rationale
      for testing global platelet function as a first-line investigation is that normal
      test results may exclude a diagnosis of platelet function disorder so that
      further specialized testing can be avoided. For this reason, global platelet
      function tests are usually initially performed at the same time as global assays
      of coagulation pathway function (prothrombin time and activated partial
      thromboplastin time, von Willebrand factor screening tests [VWF:Ag, VWF:RCo, and
      FVIII:C]) and measurement of platelet number. The most widely performed tests for
      screening platelet function disorders are currently the template bleeding time
      and the closure time within the Platelet Function Analyzer. These tests will
      therefore be considered in detail in this review, and we will discuss the
      limitations of these methods in screening individuals for platelet disorders.

PMID- 19408189
TI  - Light transmission aggregometry and ATP release for the diagnostic assessment of
      platelet function.
AB  - Light transmission aggregometry (LTA) is the gold standard for the study of
      patients with defects of platelet function. Use of LTA in clinical practice for
      predicting the risk of thrombosis or monitoring the pharmacologic effects of
      antiplatelet agents should be discouraged, because not only is the monitoring of
      treatment with antiplatelet agents (with any laboratory test) not indicated at
      present, but also the lack of standardization of the technique for LTA makes it
      additionally unsuitable for this purpose. The need for standardization of LTA has
      recently been emphasized by the results of four surveys, which showed that there
      is a wide variation in the methodology used worldwide. A modification of the
      traditional LTA is the lumiaggregometer, which measures platelet secretion in
      parallel with platelet aggregation. This technique is probably preferable to
      traditional LTA in the diagnostic workup of patients with inherited defects of
      platelet function, because it is more sensitive to the most common disorders,
      which are characterized by abnormalities of platelet secretion. LTA (or
      lumiaggregometry) is useful as a first screening test of patients with the
      clinical suspicion of defects of platelet function because it helps to provide an
      interim diagnostic hypothesis, which can then be confirmed or discounted using
      appropriate and specific tests.

PMID- 19408190
TI  - Whole blood platelet aggregometry and platelet function testing.
AB  - Platelet aggregometry has been the reference method employed to detect, diagnose,
      and monitor qualitative platelet disorders since the early 1960s.
      Lumiaggregometry and impedance-based whole blood lumiaggregometry have advantages
      over light transmittance aggregometry in that they provide for enhanced specimen
      management and increase the test sensitivity to impairment of platelet granule
      secretion. Whole blood lumiaggregometry detects and identifies congenital and
      acquired platelet plasma membrane receptor defects, metabolic pathway secretion
      disorders, and storage pool deficiency. Whole blood lumiaggregometry is also
      being applied to antiplatelet therapy monitoring and identifies aspirin and
      thienopyridine resistance. There is growing interest in using impedance-based
      whole blood lumiaggregometry for near-patient whole blood platelet analysis and
      antiplatelet therapy monitoring. This article will also discuss other whole blood
      testing processes for assessing platelet function, particularly as applied to
      assessing the effect of antiplatelet medication.

PMID- 19408191
TI  - Diagnostic evaluation of platelet function disorders in neonates and children: an
      update.
AB  - Investigation of platelet function disorders in infants and small children
      requires the collaborative efforts of clinicians and clinical laboratories. A
      detailed personal, family, and medication history, and a search for additional
      clinical phenomena may help to direct diagnostic laboratory investigations.
      Testing for these disorders in young children presents several challenges: the
      requirement of relatively large volumes of blood, lack of standardization, and
      the absence of well-established age-specific reference ranges. Neonates show the
      most notable differences in platelet function compared to older children and
      adults; the decreased platelet activation responses persist for the first 2 to 4
      weeks after delivery. Small studies of normal postneonatal pediatric populations
      have provided data on platelet function assays, including bleeding times, PFA-100
      closure times, thromboelastography, aggregation, secretion, and flow cytometry.
      The majority of these studies, comparing normal children with adults, found only
      minor differences in platelet responses measured by these assays.

PMID- 19408192
TI  - MYH9-related platelet disorders.
AB  - Myosin heavy chain 9 (MYH9)-related platelet disorders belong to the group of
      inherited thrombocytopenias. The MYH9 gene encodes the nonmuscle myosin heavy
      chain IIA (NMMHC-IIA), a cytoskeletal contractile protein. Several mutations in
      the MYH9 gene lead to premature release of platelets from the bone marrow,
      macrothrombocytopenia, and cytoplasmic inclusion bodies within leukocytes. Four
      overlapping syndromes, known as May-Hegglin anomaly, Epstein syndrome, Fechtner
      syndrome, and Sebastian platelet syndrome, describe different clinical
      manifestations of MYH9 gene mutations. Macrothrombocytopenia is present in all
      affected individuals, whereas only some develop additional clinical
      manifestations such as renal failure, hearing loss, and presenile cataracts. The
      bleeding tendency is usually moderate, with menorrhagia and easy bruising being
      most frequent. The biggest risk for the individual is inappropriate treatment due
      to misdiagnosis of chronic autoimmune thrombocytopenia. To date, 31 mutations of
      the MYH9 gene leading to macrothrombocytopenia have been identified, of which the
      upstream mutations up to amino acid approximately 1400 are more likely associated
      with syndromic manifestations than the downstream mutations. This review provides
      a short history of MYH9-related disorders, summarizes the clinical and laboratory
      characteristics, describes a diagnostic algorithm, presents recent results of
      animal models, and discusses aspects of therapeutic management.

PMID- 19408193
TI  - Genetic testing in the diagnostic evaluation of inherited platelet disorders.
AB  - Inherited disorders of platelets give rise to rare bleeding syndromes through
      defects of platelet function and/or platelet production. Platelet function
      testing by biological and immunologic assays can identify the loss or abnormal
      functioning of specific receptor systems, signaling pathways, storage organelles,
      or enzymatic activities essential for adhesion, activation, and aggregation. In
      vitro culture of megakaryocytes can help identify the origin of familial
      thrombocytopenias, and electron microscopy can point to ultrastructural defects
      and giant platelet syndromes. But a full diagnosis can only be complete when the
      genetic defect has been defined for each patient. Glanzmann thrombasthenia (GT)
      and the Bernard-Soulier syndrome are the most studied of the membrane disorders
      and a wide range of mutations identified. We will use GT as an example to show
      how genetic studies can help understand the cell biology, pathophysiology, and
      management of a group of rare diseases where many of the genetic causes remain to
      be elucidated. Knowledge of the mutation in GT and whether it affects either of
      the ITGA2B or ITGB3 genes will be essential as we enter the period where accurate
      prenatal diagnosis and gene therapy may become viable options.

PMID- 19408194
TI  - Role of platelet electron microscopy in the diagnosis of platelet disorders.
AB  - The electron microscope has proved to be a useful tool to study and understand
      the biology of platelets and to classify many platelet disorders. After a
      technical overview, this article reviews syndromes originating from platelet
      organelle, cytoskeleton, and membrane defects for which electron microscopy plays
      a role in the diagnostic process, such as gray platelet syndrome, Paris-Trousseau
      syndrome, storage pool diseases, MYH9-related thrombocytopenias, or Wiskott
      Aldrich syndrome. Particular focus is given to the ultrastructural aspect of
      platelets in these disorders.

PMID- 19408195
TI  - Glycoprotein analysis for the diagnostic evaluation of platelet disorders.
AB  - Platelet glycoproteins subserve a wide variety of critical functions in blood
      platelets. Congenital deficiencies or functional abnormalities in platelet
      glycoproteins may produce serious bleeding disorders such as Glanzmann
      thrombasthenia or Bernard-Soulier syndrome. Other hematologic disorders, such as
      Fanconi anemia and various myelodysplastic syndromes, may also be associated with
      abnormalities in platelet glycoproteins. Additionally, several acquired disorders
      involving the major platelet glycoproteins are increasingly being recognized. The
      large number of techniques, now available to characterize platelet glycoprotein
      disorders, reflect the many advances in biochemistry, molecular analysis, flow
      cytometry, and, most recently, proteomics. The application of platelet
      glycoprotein analysis to a wide range of clinical disorders is reviewed in this
      article.

PMID- 19408196
TI  - Impaired platelet procoagulant mechanisms in patients with bleeding disorders.
AB  - Activated platelets contribute to the arrest of bleeding by forming aggregates at
      sites of vascular injury and by providing a surface for assembling enzyme
      complexes involved in fibrin formation (platelet procoagulant activity; PCA).
      Impairment in the latter property of platelets has been observed in some
      disorders of hemostasis. In Scott syndrome, there is a defect in membrane
      vesiculation and in the surface expression of phosphatidylserine (PS), the
      phospholipid that is necessary for assembling the factor VIIIa/IXa (tenase) and
      factor Va/Xa (prothrombinase) complexes involved in thrombin formation. A family
      with an isolated defect in vesiculation, but normal prothrombinase activity, has
      also been reported. In the Quebec platelet disorder, overexpression of the
      fibrinolytic enzyme urokinase-type plasminogen activator results in the
      degradation of alpha-granule proteins, including factor V, and a specific
      abnormality in platelet factor V is the basis for the prothrombinase defect in
      platelet factor V-New York. The impaired prothrombinase activity in patients with
      delta-storage pool deficiency may be due to a failure to provide sufficient
      amounts of secreted adenine nucleotides which, when bound to P2 purinergic
      receptors, are necessary to maintain the intracellular Ca (2+) levels that are
      required for the surface expression of PS. Platelet prothrombinase activity and
      thrombin potential in patients with Glanzmann thrombasthenia (GPIIb-IIIa
      deficiency) may be decreased, normal, or increased, depending on the experimental
      conditions, for reasons that are not currently clear. The most consistent
      platelet PCA abnormality in the Bernard-Soulier syndrome (GPIb-complex
      deficiency) is an abnormally short serum prothrombin time, associated with a
      defect in the process by which an interaction between fibrin, von Willebrand
      factor, and GPIb promotes PCA.

PMID- 19408197
TI  - The level of laboratory testing required for diagnosis or exclusion of a platelet
      function disorder using platelet aggregation and secretion assays.
AB  - The major advances from research on platelet molecular and cell biology,
      physiology, and pathophysiology over the past decades have not been adequately
      translated to clinical laboratory diagnosis. Hereditary platelet function
      disorders (PFDs) are at least as prevalent in the general population as von
      Willebrand disease (VWD) although PFDs tend not be as well recognized or
      evaluated. Clinical mucous and skin bleeding in patients with PFDs is prototypic
      of primary hemostasis disorders, and the bleeding pattern is not distinguishable
      from that of other primary hemostasis disorders such as VWD. However, different
      treatment needs, between these discrete disorders, make a precise diagnosis
      mandatory. Currently, clinicians receive reliable laboratory reports when testing
      patients with severe PFDs, such as Glanzmann thrombasthenia and Bernard-Soulier
      syndrome, due to the distinctive laboratory defects that these disorders present,
      together with the availability of differential diagnostic tests. This is not the
      case for the majority of PFDs generically classified as "platelet secretion
      disorders," which are a heterogeneous group of "mild bleeding disorders," for
      which there are not universally accepted diagnostic criteria. An important reason
      for robust diagnostic tests is the high proportion (more than 50% in some
      reports) of patients with unequivocal bleeding who have no precise diagnosis
      established after a complete laboratory workup. It is paradoxical that the
      current "gold standard" test for PFD diagnosis, light transmission aggregometry
      (LTA), has not been standardized after more than four decades of worldwide
      clinical use. This review describes current diagnostic assays for PFD in a
      clinical hemostasis laboratory, relating these with current knowledge on platelet
      function and pathophysiology. Special emphasis will be given to LTA and platelet
      secretion tests, as well as to the reasons why sensitive tests are needed to
      explore the lesser known participation of platelets in blood clotting and
      fibrinolytic processes.

PMID- 19408212
TI  - [High-resolution imaging of the layers of the gastrointestinal wall of pig and
      human specimens using an endoluminal MR receiver coil: correlation to histology].
AB  - PURPOSE: High-resolution MR imaging of the layers of the gastrointestinal wall to
      provide a foundation for tumor staging based on morphological criteria. MATERIALS
      AND METHODS: Over a period of 12 months, miscellaneous parts of the
      gastrointestinal tract of 15 human specimens and 30 porcine specimens were
      scanned using a 1.5 Tesla clinical MRI scanner combined with an endoluminal
      receiver coil. The sequences used were T 1-weighted opposed-phase, T 2-weighted
      turbo spin echo with fat saturation and fast T 2-weighted inversion recovery. The
      number of differentiable layers, their width and the signal intensity were
      documented. Then, the results were compared with histological specimens in order
      to link the imaged wall layers to the anatomical layers. Spearman's Rank
      Correlation was used to determine the soundness of the link between the images
      and their related histology. RESULTS: For both human and animal specimens, the
      MRI scanning produced 3 to 5, maximum 6 (pig), differentiable layers. The mucosa,
      submucosa and muscularis could be differentiated with a hyperintense, hypointense
      and intermediary signal, respectively. The subserosal layer displayed a
      hypointense signal. CONCLUSION: High-resolution MRI is able to produce
      differentiable images of the anatomical layers of the gastrointestinal wall in
      both humans and pigs. Accordingly, it is possible to use MR imaging to diagnose
      the extent of local tumor infiltration of the gastrointestinal wall.

PMID- 19408213
TI  - Value of MDCT in preoperative local staging of rectal cancer for predicting the
      necessity for neoadjuvant radiochemotherapy.
AB  - PURPOSE: Neoadjuvant therapy may reduce local rectal cancer recurrence after
      total mesorectum extirpation. This study was performed to assess whether multi
      detector row CT (MDCT) is capable of reliably differentiating UICC I (surgery)
      from UICC II-IV (neoadjuvant therapy). MATERIALS AND METHODS: 29 patients
      underwent preoperative MDCT of the abdomen in a portal venous phase. Two blinded
      readers independently evaluated the datasets on a dedicated workstation using
      axial and coronal reformations. Local tumor extension (T), nodal status (N) and
      distant metastases (M) were evaluated and the UICC stage was determined. Findings
      were correlated with postoperative histology. RESULTS: Histologically, 9 patients
      were UICC I; 20 UICC > I (II: 7; III: 11; IV: 2). Reader 1 correctly identified 3
      / 9 as UICC I, overstaged 6 / 9, and correctly staged 20 / 20 as UICC > I. Reader
      2 correctly identified 4 / 9 as UICC I, overstaged 5 / 9, understaged 4 / 20 and
      correctly staged 16 / 20 as UICC > I (PPV UICC I 100 % [50 %] reader 1 [reader
      2], NPV 77 % [76 %], accuracy 79 % [69 %]). Reasons for overstaging by reader 1
      (reader 2) included false-positive lymph nodes (LN) in 5 (5), overgrading T 1
      tumors as T 3 in 1(0), and T overgrading in 4 / 5 (2 / 5) patients with false
      positive LN. CONCLUSION: MDCT failed to reliably identify UICC I in rectal cancer
      patients. Therefore, a strategy based solely on MDCT to identify patients who
      would benefit from neoadjuvant therapy does not seem appropriate.

PMID- 19408215
TI  - First and early second trimester fetal heart scanning.
AB  - This review describes the recent advances in terms of visualization and diagnosis
      of first and early second trimester fetal echocardiography.

PMID- 19408214
TI  - Plasma CRP levels in premenopausal women with major depression: a 12-month
      controlled study.
AB  - C-reactive protein (CRP), an inflammatory marker of cardiovascular risk, is often
      elevated in major depressive disorder (MDD). The magnitude and consistency of
      this elevation have not been previously characterized in premenopausal women with
      MDD. The aim of the study was to prospectively assess plasma CRP levels, body
      composition, endocrine and metabolic parameters, and depressive status in
      premenopausal women with MDD (n=77) and controls (n=41), aged 21 to 45. Women
      were enrolled in a 12-month, controlled study of bone turnover, the P.O.W.E.R. (
      Premenopausal, Osteoporosis, Women, Al Endronate, Dep Ression) Study. Blood
      samples were taken at Baseline, Month 6, and Month 12. Most subjects with MDD
      were in clinical remission. These women tended to have consistently higher CRP
      levels than controls over 12 months (p=0.077). BMI was positively related to
      log[CRP] in women with MDD only. Nine women with MDD had CRP levels greater than
      10 mg/l, a value associated with a very high cardiovascular risk. This subset was
      obese and had significantly higher triglycerides, total cholesterol, LDL
      cholesterol, fasting insulin, and HOMA-IR than the rest of women with MDD. The
      variations in CRP levels over time were high (intra- and inter-individual
      coefficients of variations of approximately 30-50% and approximately 70-140%,
      respectively). No control had CRP levels greater than 10 mg/l. Depression was
      associated with increased plasma CRP in women with MDD. The clinical significance
      of abnormal plasma CRP for cardiovascular risk needs to be assessed in large
      prospective studies of women with depression.

PMID- 19408216
TI  - Neonatal gastrointestinal mucormycosis clinically mimicking necrotizing
      enterocolitis.

PMID- 19408219
TI  - [Vitamin C as contrast agent in diagnosis of salivary duct obstruction].
AB  - In obstructive diseases of the salivary glands ultrasound is routinely used. In
      obstructive sialadenitis of the parotid and submandibular glands, diagnostic
      assessment of the origin and location of impediment is sometimes difficult. We
      studied sonographic visibility of the duct before and after stimulation with oral
      ascorbic acid (Vitamin C), the diagnosis compared to sialoendoscopy. In 43
      patients with obstructive salivary gland diseases ultrasound examination of the
      parotid and submandibular glands was carried out before and after oral ascorbic
      acid stimulation. Before stimulation the duct system was depicted in 27 patients
      (63%). After ascorbic acid stimulation the duct system became visible in now 41
      patients (95%). Application of ascorbic acid as part of ultrasound assessment
      improves diagnostic capabilities in patients with obstructive salivary gland
      diseases.

PMID- 19408240
TI  - Structural elucidation and NMR spectral assignment of three new furostanol
      saponins from the roots of Tupistra chinensis.
AB  - Three new furostanol saponins (1-3) were isolated from the roots of Tupistra
      chinensis (T. chinensis). And their structures were elucidated on the basis of
      NMR and mass spectrometry (MS) spectral analysis.

PMID- 19408239
TI  - Agar-gelatin hybrid sponge-induced three-dimensional in vitro 'liver-like' HepG2
      spheroids for the evaluation of drug cytotoxicity.
AB  - Agar-gelatin hybrid sponges were used as scaffolds to induce the formation of
      three-dimensional (3D) spheroids of HepG2 cells. Agar and gelatin in 2:1 ratio
      were used to make films and sponges. The cell adhesive properties of the films
      were evaluated by the attachment kinetics. The growth kinetics of HepG2 cells was
      studied using MTT assay and morphology of the 3D spheroids was observed through
      inverted optical microscopy. The liver cell-specific functions of the 3D
      spheroids were evaluated in terms of albumin secretion and urea synthesis.
      Paracetamol was used as a model drug to investigate the use of these 3D spheroids
      in the preliminary cytotoxicity evaluation of drugs. The results showed that the
      agar-gelatin hybrid sponges induced the formation of 3D HepG2 spheroids with
      significant liver-specific functions. These spheroids exhibited higher amounts of
      albumin and urea synthesis than the control monolayer culture. These 3D spheroids
      were found to be more sensitive to the drug (TCIC(50) value of 4.6 mM) than the
      control monolayer (TCIC(50) value of 6.2 mM). The study shows that agar-gelatin
      induced HepG2 3D spheroids can be used for the preliminary evaluation of the
      toxicity of drugs and chemicals.

PMID- 19408241
TI  - Impact of missing data on type 1 error rates in non-inferiority trials.
AB  - In this paper, a simulation study is conducted to systematically investigate the
      impact of different types of missing data on six different statistical analyses:
      four different likelihood-based linear mixed effects models and analysis of
      covariance (ANCOVA) using two different data sets, in non-inferiority trial
      settings for the analysis of longitudinal continuous data. ANCOVA is valid when
      the missing data are completely at random. Likelihood-based linear mixed effects
      model approaches are valid when the missing data are at random. Pattern-mixture
      model (PMM) was developed to incorporate non-random missing mechanism. Our
      simulations suggest that two linear mixed effects models using unstructured
      covariance matrix for within-subject correlation with no random effects or first
      order autoregressive covariance matrix for within-subject correlation with random
      coefficient effects provide well control of type 1 error (T1E) rate when the
      missing data are completely at random or at random. ANCOVA using last observation
      carried forward imputed data set is the worst method in terms of bias and T1E
      rate. PMM does not show much improvement on controlling T1E rate compared with
      other linear mixed effects models when the missing data are not at random but is
      markedly inferior when the missing data are at random.

PMID- 19408242
TI  - Sulfur dioxide and benzo(a)pyrene modulates CYP1A and tumor-related gene
      expression in rat liver.
AB  - Sulfur dioxide (SO(2)) and benzo(a)pyrene (B(a)P) are common industrial and
      environmental contaminants. However, few data are available on the effects of
      SO(2) on proto-oncogenes and tumor suppressor genes, as well as the interactions
      between SO(2) and other xenobiotics regulating proto-oncogenes or tumor
      suppressor genes expression. To investigate the interactions between SO(2) and
      B(a)P, male Wistar rats were exposed to intratracheally instilled with B(a)P or
      SO(2) inhalation alone or together. We detected mRNA expression of CYP1A1 and
      1A2, 7-ethoxyresorufin O-deethylase (EROD), and methoxyresorufin O-demethylase
      (MROD) activities in livers. The mRNA and protein levels of several cancer
      related genes were analyzed in livers by real-time RT-PCR and Western blot,
      respectively. The EROD/MROD activities and CYP1A1/2 expression were down
      regulated by SO(2) but up-regulated by B(a)P alone. Exposure of SO(2) alone
      induced c-fos, c-jun, c-myc, H-ras, and p53 expression, and depressed p16 and Rb
      expression in livers. The effects of B(a)P on the above gene were similar to
      SO(2) except c-fos expression. Furthermore, SO(2) + B(a)P exposure increased the
      expression of c-fos, c-jun, c-myc, and p53, and decreased p16 and Rb expression
      in livers compared with exposed to SO(2) or B(a)P alone. However, no synergistic
      effects were observed on H-ras and CYP1A1/2 after SO(2) + B(a)P exposure. Our
      findings indicate that multiple cell cycle regulatory proteins play key roles in
      the toxicity of SO(2) and B(a)P in livers. It might involve the activation of c
      fos, c-jun, c-myc, and p53. And p16-Rb pathway might also participate in the
      progress. Although the gene products we studied are classed as oncogenes and
      tumor suppressor genes, their functions actually relate to more general processes
      of control of cell proliferation, survival, and/or apoptosis.

PMID- 19408243
TI  - Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in
      FOXP3 expression.
AB  - Treg are the main mediators of dominant tolerance. Their mechanisms of action and
      applications are subjects of considerable debate currently. However, a human
      microRNA (miR) Treg signature has not been described yet. We investigated human
      natural Treg and identified a signature composed of five miR (21, 31, 125a, 181c
      and 374). Among those, two were considerably under-expressed (miR-31 and miR
      125a). We identified a functional target sequence for miR-31 in the 3'
      untranslated region (3' UTR) of FOXP3 mRNA. Using lentiviral transduction of
      fresh cord blood T cells, we demonstrated that miR-31 and miR-21 had an effect on
      FOXP3 expression levels. We showed that miR-31 negatively regulates FOXP3
      expression by binding directly to its potential target site in the 3' UTR of
      FOXP3 mRNA. We next demonstrated that miR-21 acted as a positive, though
      indirect, regulator of FOXP3 expression. Transduction of the remaining three miR
      had no direct effect on FOXP3 expression or on the phenotype and will remain the
      subject of future investigations. In conclusion, not only have we identified and
      validated a miR signature for human natural Treg, but also unveiled some of the
      mechanisms by which this signature was related to the control of FOXP3 expression
      in these cells.

PMID- 19408244
TI  - It's a long way from amphioxus: descendants of the earliest chordate.
AB  - The origin of chordates and the consequent genesis of vertebrates were major
      events in natural history. The amphioxus (lancelet) is now recognised as the
      closest extant relative to the stem chordate and is the only living invertebrate
      that retains a vertebrate-like development and body plan through its lifespan,
      despite more than 500 million years of independent evolution from the stem
      vertebrate. The inspiring data coming from its recently sequenced genome confirms
      that amphioxus has a prototypical chordate genome with respect to gene content
      and structure, and even chromosomal organisation. Pushed by joint efforts of
      amphioxus researchers, amphioxus is now entering a new era, namely its maturation
      as a laboratory model, through the availability of a large amount of molecular
      data and the advent of experimental manipulation of the embryo. These two facts
      may well serve to illuminate the hidden secrets of the genetic changes that
      generated, among other vertebrates, ourselves.

PMID- 19408245
TI  - Mitochondrial bioenergetics as a major motive force of speciation.
AB  - Mitochondrial bioenergetics plays a key role in multiple basic cellular
      processes, such as energy production, nucleotide biosynthesis, and iron
      metabolism. It is an essential system for animals' life and death (apoptosis) and
      it is required for embryo development. This, in conjunction with its being
      subjected to adaptive processes in multiple species and its gene products being
      involved in the formation of reproductive barriers in animals, raises the
      possibility that mitochondrial bioenergetics could be a candidate genetic
      mechanism of speciation. Here, we discuss genetic and biochemical evidence for
      the possible involvement of this unique system, encoded by two genomes (the
      mitochondrial and nuclear genomes), that differ by an order of magnitude in their
      mutation rates in processes leading to speciation events.

PMID- 19408246
TI  - Epidemiology of a tick-borne viral infection: theoretical insights and practical
      implications for public health.
AB  - The morbidity of tick-borne encephalitis (TBE) varies yearly by as much as 10
      fold among the people of Western Siberia. This long-term variation is dependent
      on many factors such as the density of the tick populations, the prevalence of
      TBE virus (TBEV) among sub-adult ticks, the yearly virulence of the TBEV, and
      prophylactic measures. Here we highlight the role of small mammal hosts in the
      circulation of TBEV through the ecosystem. Refining classical models of non
      viremic horizontal transmission, we emphasize the recently understood fact that
      the physiological and immunological status of the small mammal hosts affects the
      tick and virus-host interactions. In addition to its theoretical interest, our
      approach may lead to some practical improvements in the precision of
      epidemiological forecasts and perhaps in forestalling the severity of outbreaks
      of TBE, or, at least, in forewarning medical authorities and the general public
      of impending TBE outbreaks.

PMID- 19408248
TI  - Regioselective and sequential reactivity of activated 2,5-diketopiperazines.
AB  - The electrophilic reactivity of Boc-DKPs has been studied. Thanks to Boc
      activation, the opening ability of carbonyl lactam groups is enhanced. According
      to experimental conditions, this enabled the synthesis of Boc-amino acid
      derivatives or original dipeptides via a regioselective and sequential way.

PMID- 19408247
TI  - The effect of beta-methylation on the conformation of alpha, beta
      dehydrophenylalanine: a DFT study.
AB  - Dehydroamino acids are non-coded amino acids that offer unique conformational
      properties. Dehydrophenylalanine (DeltaPhe) is most commonly used to modify
      bioactive peptides to constrain the topography of the phenyl ring in the side
      chain, which commonly serves as a pharmacophore. The Ramachandran maps (in the
      gas phase and in CHCl(3) mimicking environments) of DeltaPhe analogues with
      methyl groups at the beta position of the side chain as well as at the C-terminal
      amide were calculated using the B3LYP/6-31 + G** method. Unexpectedly, beta
      methylation alone results in an increase of conformational freedom of the
      affected DeltaPhe residue. However, further modification by introducing an
      additional methyl group at C-terminal methyl amide results in a steric crowding
      that fixes the torsion angle psi of all conformers to the value 123 degrees ,
      regardless of the Z or E position of the phenyl ring. The number of conformers is
      reduced and the accessible conformational space of the residues is very limited.
      In particular, (Z)-Delta(betaMe)Phe with the tertiary C-terminal amide can be
      classified as the amino acid derivative that has a single conformational state as
      it seems to adopt only the beta conformation.

PMID- 19408249
TI  - A new method for the determination of the relative affinity of a ligand against
      various DNA sequences by electrospray ionization mass spectrometry. Application
      to a polyamide minor groove binder.
AB  - A new method for the determination of the relative affinity of a ligand against
      various dsDNA sequences is presented by using electrospray ionization time-of
      flight mass spectrometry (ESI-QTOF) mass spectrometry. The principle is described
      here through the complexation of double-stranded DNA by a polyamide ligand
      including twelve N-methylpyrrole rings. However this method could be applied to
      other ligands especially when dissociation constants (Kd) are in nanomolar range.
      This method does not require knowing the ligand concentration accurately. It
      allows determination of the relative affinity of a ligand against various dsDNA
      sequences for 1 : 1 complex stoichiometries in a quick manner without labeling.

PMID- 19408250
TI  - Effect of deviation of nuchal translucency measurements on the performance of
      screening for trisomy 21.
AB  - OBJECTIVES: To examine the effect of deviations in median nuchal translucency
      thickness (NT) and the spread in measurements on the performance of screening for
      trisomy 21 by maternal age and fetal NT, and by maternal age, fetal NT and
      maternal serum biochemistry. METHODS: We simulated the NT and multiples of the
      median values for pregnancy-associated plasma protein-A (PAPP-A) and free beta
      human chorionic gonadotropin (beta-hCG) for 500 000 euploid and 500 000 trisomy
      21 pregnancies at 12 weeks of gestation. Detection rates for trisomy 21 and false
      positive rates were calculated without adjustments in NT and by adding or
      subtracting values ranging from 0.1 to 1.0 mm to each observed measurement. In
      addition, the effects of variation in the scatter of NT measurements were
      examined by applying a multiplicative factor ranging from 0.5 to 2 to the SD.
      RESULTS: The detection rate of trisomy 21 for a fixed false-positive rate of 3%
      in screening by maternal age and fetal NT was 72%, and in screening by maternal
      age, fetal NT and serum free beta-hCG and PAPP-A it was 86%. A consistent
      underestimate or overestimate in the measured NT reduced the detection rate of
      trisomy 21 for a fixed-false positive rate. At a fixed screen-positive cut-off an
      underestimate in fetal NT reduced the detection rate whereas an overestimate in
      NT increased the false-positive rate. A widening in the scatter of measurements
      had only a small impact on the detection rate but it caused a major increase in
      the false-positive rate. CONCLUSIONS: High performance of screening necessitates
      appropriate measurement of fetal NT. This paper demonstrates the effect of
      deviations in the median and SD of NT from the expected on the performance of
      screening and can form the basis of audit of results of individual sonographers.

PMID- 19408251
TI  - Testing three evolutionary models of the demographic transition: Patterns of
      fertility and age at marriage in urban South India.
AB  - Over the last three decades many authors have addressed the demographic
      transition from the perspective of evolutionary theory. Some authors have
      emphasized parental investment factors such as the costs of raising children,
      others have emphasized the effects of mortality and other forms of risk, and
      others have emphasized the biased transmission of cultural norms from people of
      high status. Yet the literature says little about the relative strengths of each
      of these types of motivations or about which ones are more likely to serve as the
      primary impetus for large-scale demographic change. In this paper, I examine how
      each of these factors has influenced the demographic transition in urban South
      India during the course of the 20th century using two measures of fertility
      transition: number of surviving children and age at marriage. I find that
      investment-related, risk-related, and cultural transmission predictors all have
      significant individual effects on the outcome variables, which persist when they
      are entered in combination. When the three types of predictors are compared,
      however, investment-related models appear to provide more robust explanations for
      patterns in both fertility and age of marriage.

PMID- 19408252
TI  - Glycerophospholipid profiling by high-performance liquid chromatography/mass
      spectrometry using exact mass measurements and multi-stage mass spectrometric
      fragmentation experiments in parallel.
AB  - A profiling method for glycerophospholipids (GPs) in biological samples was
      developed using reversed-phase high-performance liquid chromatography (RP-HPLC)
      coupled to hybrid linear ion trap-Fourier transform ion cyclotron resonance mass
      spectrometry (LIT-FTICRMS) with electrospray ionization (ESI) in the negative
      ionization mode. The method allowed qualitative (identification and structure
      elucidation) and relative quantitative determination of various classes of GPs
      including phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols,
      phosphatidylserines, phosphatidic acids, phosphatidylglycerols, and cardiolipins
      in a single experiment. Chromatographic separation was optimized by the
      examination of different buffer systems and special emphasis was paid on the
      detection by ESI-MS. The hybrid LIT-FTICRMS system was operated in the data
      dependent mode, switching automatically between FTICRMS survey scans and LIT
      MS/MS experiments. Thereby, exact masses for elemental composition determination
      and fragmentation data for identification and assignment of fatty acid residues
      are provided at the same time. The low absolute instrumental limits of detection
      (0.05 pmol for phosphatidylglycerol to 1 pmol for phosphatidic acid) complemented
      by a linear dynamic range of 1.5 to 2.5 orders of magnitude facilitated the
      relative quantification of GP species in a lipid extract from Saccharomyces
      cerevisiae. The developed method is a valuable tool for in-depth GP profiling of
      biological systems.

PMID- 19408253
TI  - Structural characterization and identification of C(19)- and C(20)-diterpenoid
      alkaloids in roots of Aconitum carmichaeli by rapid-resolution liquid
      chromatography coupled with time-of-flight mass spectrometry.
AB  - Aconite alkaloids from the roots of Aconitum carmichaeli (Fuzi, in Chinese) have
      been investigated by rapid-resolution liquid chromatography coupled with time-of
      flight mass spectrometry (TOFMS) in positive mode. With dynamic adjustment of the
      key role as fragmentor voltage in TOFMS, an efficient transmission of the ions
      was achieved to obtain the best sensitivity for providing the molecular formula
      for each analyte, and abundant fragment ions for structural information. Fifteen
      authentic standards isolated from Fuzi with various structures were first
      characterized by TOFMS, including diester-diterpenoid alkaloids (DDAs), monoester
      diterpenoid alkaloids (MDAs), alkylol amine-diterpenoid alkaloids (ADAs),
      veatchine-type alkaloids and atisine-type alkaloids. Fragmentation rules and key
      diagnostic fragment ions have been summarized, and possible pathways of
      fragmentation have been proposed. By accurate mass measurements within 5 ppm
      error for each ion, 30 C(19)-diterpenoid alkaloids including 10 DDAs, 3 MDAs, 9
      ADAs and 8 other type alkaloids, and 8 C(20)-diterpenoid alkaloids including 4
      veatchine-type alkaloids and 4 atisine-type alkaloids could be identified in a
      methanolic extract of Fuzi. Some isomers of aconite alkaloids were also
      differentiated. Based on the differences between their fragmentation pathways and
      special fragment ions, each type of aconite alkaloids was differentiated.

PMID- 19408254
TI  - Obestatin/ghrelin ratio: a new activity index in inflammatory bowel diseases.
AB  - BACKGROUND: The aim was to determine obestatin and ghrelin serum levels and their
      ratio in inflammatory bowel disease (IBD) patients. METHODS: We measured the
      ghrelin and obestatin levels of 31 Crohn's disease patients and 22 patients with
      ulcerative colitis using a radioimmunoassay method. Circulating levels of the 2
      hormones and their ratio were correlated with the disease type and activity,
      disease localization, and treatment. RESULTS: The mean ghrelin value was
      statistically significantly higher in patients with active disease (402.4 +/-
      462.6 pg/mL) than in patients in remission (148.2 +/- 59.6 pg/mL) P = 0.0290,
      alpha = 0.05, whereas obestatin mean values were not (217.4 +/- 59.8 pg/mL in
      active disease and 189.0 +/- 46.8 pg/mL in patients with inactive disease P =
      0.0607). When we evaluated the obestatin/ghrelin ratio between active and
      inactive disease, it was found that the ratio in active disease was statistically
      significantly lower (0.8 +/- 0.3) than in patients in remission (1.4 +/- 0.3) P <
      0.001, alpha = 0.05. There is also a statistically significantly correlation
      between obestatin/ghrelin ratio and disease activity (P < 0,001). CONCLUSIONS:
      Ghrelin and obestatin seem to play a significant role in IBD pathogenesis.
      Further studies are needed to elucidate the role of these hormones as new
      biological markers of activity of IBD.

PMID- 19408256
TI  - Liquid-phase exfoliation of graphite towards solubilized graphenes.

PMID- 19408255
TI  - Extending DerSimonian and Laird's methodology to perform multivariate random
      effects meta-analyses.
AB  - Multivariate meta-analysis is increasingly used in medical statistics. In the
      univariate setting, the non-iterative method proposed by DerSimonian and Laird is
      a simple and now standard way of performing random effects meta-analyses. We
      propose a natural and easily implemented multivariate extension of this procedure
      which is accessible to applied researchers and provides a much less
      computationally intensive alternative to existing methods. In a simulation study,
      the proposed procedure performs similarly in almost all ways to the more
      established iterative restricted maximum likelihood approach. The method is
      applied to some real data sets and an extension to multivariate meta-regression
      is described.

PMID- 19408257
TI  - Enhancement-mode silicon nanowire field-effect transistors on plastic substrates.

PMID- 19408259
TI  - Personalized energy: the home as a solar power station and solar gas station.
AB  - Point-of-use solar energy would generate the exact amount of energy any one
      individual needs, at the location where it is needed. Such a means of energy
      supply would create a revolution in society's approach to energy use, and allow a
      more level playing field for all. This Viewpoint considers some of the key
      enablers for this technology.

PMID- 19408260
TI  - The transformative innovations needed by green chemistry for sustainability.
AB  - Green chemistry is discussed as a central design framework for the implementation
      of new scientific knowledge into everyday life. When addressed in such a manner,
      sustainability and economic viability are not necessarily mutually exclusive.

PMID- 19408258
TI  - Light-induced temperature transitions in biodegradable polymer and nanorod
      composites.

PMID- 19408262
TI  - Anomalous odd-even effects in columnar and smectic phases of discotic
      tetraphenylenes.
AB  - Rather uncommon but pronounced odd-even effects in the clearing temperatures of
      liquid crystals are found for three new homologous series of discotic
      tetraphenylenes [figure: see text]. Detailed similarities to the well-known odd
      even effects in calmitic mesogens point towards a more general understanding of
      odd-even effects in liquid crystals.The phase transition temperatures in many
      homologous series of liquid crystals show odd-even effects similar to the well
      known odd-even effects in non-mesogenic organic compounds like carboxylic acids.
      For discotic liquid crystals only a few series with a sufficient number of
      consecutive homologues are available and only a small part of these series show
      odd-even effects at all. We now synthesized and investigated three series of
      discotic tetraphenylenes each ranging from the n=7 to the n=16 homologues. For
      these compounds an anomalous odd-even effect is found: The ascending and
      descending transition temperatures with increasing number of methylene groups in
      the side chains exhibit an inversion of this alternation which is always found
      between the n=12 and n=14 homologues. An overview of odd-even effects in liquid
      crystals is presented and we discuss the nature and the origin of odd-even effect
      in discotic mesogens.

PMID- 19408261
TI  - Thermodynamic and computational studies on the binding of p53-derived peptides
      and peptidomimetic inhibitors to HDM2.
AB  - Helix power: The binding interactions of linear and constrained beta-hairpin
      shaped peptides with HDM2 were compared by using experimental and theoretical
      methods. The entropic advantages enjoyed by the constrained peptides were found
      to be largely offset by reduced enthalpic contributions to binding of the cyclic
      mimetics. Formation of hydrogen bonds upon helix folding could contribute
      significantly to the enhanced enthalpy observed in binding of the linear
      peptides.The human double minute 2 protein (HDM2) binds a short peptide derived
      from the N terminus of the tumor-suppressor protein, p53. This peptide (p53
      residues 15-29) is flexible in free solution, but upon binding to HDM2 it folds
      into an amphipathic alpha-helical conformation. Three residues along one face of
      the p53 helix (Phe19, Trp23, and Leu26) dock into hydrophobic pockets on the
      surface of HDM2. A conformationally constrained cyclic beta-hairpin
      peptidomimetic of p53, with residues Phe1, 6-chloro-Trp3, and Leu4 in one strand
      of the beta-hairpin, was shown earlier to dock into the same pockets on HDM2.
      Here, we show by isothermal titration calorimetry that the entropy loss upon
      binding of the constrained peptide to HDM2 is, as would be expected, much lower
      (TDeltaS approximately 10 kcal mol(-1) at 300 K) than that for the linear
      peptide. However, the entropic advantage enjoyed by the constrained peptide is
      largely offset by a reduced enthalpic contribution, relative to the linear
      peptide, to binding of the cyclic mimetic. To explore the electronic nature of
      the interactions between the energetically important residues in each ligand and
      HDM2, hybrid quantum mechanical and electrostatic Poisson-Boltzmann computational
      studies were performed. The calculations reveal that significant stabilizing van
      der Waals interactions and polarization effects occur between the Trp side chain
      in each ligand and aromatic and aliphatic residues in HDM2. These stabilizing
      interactions are enhanced when a 6-chloro substituent is incorporated into the
      Trp, in agreement with the experimental studies. In addition, the calculations
      suggest that at least one stabilizing hydrogen bond is formed, between the Trp
      indole-NH in both ligands and HDM2. Other hydrogen-bonding interactions also
      arise, however, along the alpha-helical backbone of the linear peptide upon
      binding to HDM2, but are not mimicked in the constrained inhibitor-HDM2 complex.
      The formation of these hydrogen bonds upon helix folding could contribute
      significantly to the enhanced enthalpy observed in binding of the linear peptide
      to HDM2.

PMID- 19408263
TI  - Towards the efficient, total glycan utilization of biomass.
AB  - From biomass to mass transportation: Waste biomass (newspaper, corn stover,
      straw, and wood) is converted into biofuel precursors and value-added products in
      excellent yield using a simple, inexpensive process involving concurrent
      hydrolysis, dehydration, and substitution reactions in a biphasic reactor. The
      hemicellulose fraction of these substrates is simultaneously converted into
      furfural, and together these constitute an efficient means for the total
      exploitation of the carbohydrate content of biomass.

PMID- 19408264
TI  - The monoammoniate of lithium borohydride, Li(NH3)BH4: an effective ammonia
      storage compound.
AB  - Lithium borohydride absorbs anhydrous ammonia to form four stable ammoniates;
      Li(NH(3))(n)BH(4), mono-, di-, tri-, and tertraammoniate. This paper focuses on
      the monoammoniate, Li(NH(3))BH(4), which is readily formed on exposure of LiBH(4)
      to ammonia at room temperature and pressure. Ammonia loss from Li(NH(3))BH(4)
      commences around 40 degrees C and the compound transforms directly to LiBH(4).
      The crystal structure of Li(NH(3))BH(4) is reported here for the first time. Its
      close structural relationship with LiBH(4) provides a clear insight into the
      facile nature and mechanism of ammonia uptake and loss. These materials not only
      represent an excellent high weight-percent ammonia system but are also
      potentially important hydrogen stores.

PMID- 19408265
TI  - From iron oxides to infections.
AB  - Cellular electron transfer under diverse anaerobic conditions is a primary topic
      of research conducted by the Newman group. In this Viewpoint, a summary is given
      of how a geobiological approach has been used to investigate these processes.

PMID- 19408266
TI  - A xenon-129 biosensor for monitoring MHC-peptide interactions.
AB  - Caged in: The formation of a complex between a peptide ligand and a major
      histocompatibility complex (MHC) class II protein is detected by a (129)Xe
      biosensor. Cryptophane molecules that trap Xe atoms are modified with a
      hemagglutinin (HA) peptide, which binds to the MHC protein. The interaction can
      be monitored by an NMR chemical shift change of cage-HA bound (129)Xe.

PMID- 19408268
TI  - Total synthesis and stereochemical assignment of micrococcin P1.
AB  - Fifty years after the discovery of the thiopeptide antibiotic micrococcin P1, the
      constitutional and stereochemical uncertainties concerning its structure have
      been lifted with its total synthesis and absolute stereochemical assignment (see
      picture).

PMID- 19408269
TI  - Linear pi-acceptor-templated dynamic clipping to macrobicycles and [2]rotaxanes.
AB  - Cage me! A linear dumbbell-shaped bipyridinium molecule can template cage
      formation around itself through sixfold imine bond formation to give an
      interlocked [2]rotaxane as the single product (see picture). This highly
      efficient [2+3] clipping occurs despite the symmetry mismatch between the
      template and the formed macrobicycle.

PMID- 19408267
TI  - Development of a fluorescent Pb2+ sensor.
AB  - A real turn-on: The emission intensity of heterocycle 1 increases upon binding to
      Pb(2+). Thus, 1 acts as a small-molecule "turn-on" fluorescent sensor for lead.
      The sensor is highly selective and is functional over a wide range of pH values.

PMID- 19408270
TI  - Spontaneous formation of giant unilamellar vesicles from microdroplets of a
      polyion complex by thermally induced phase separation.
AB  - Water pump: Polyion complex (PIC) vesicles are spontaneously formed from PIC
      microdroplets, which are formed by mixing cationic and anionic polymers (see
      picture). The formation process can be reversibly controlled by local heating
      with a focused infrared laser that triggers microphase separation and subsequent
      water influx. The size of the resulting giant unilamellar vesicles is determined
      by the initial size of the PIC droplets.

PMID- 19408272
TI  - Koop Lammertsma.
AB  - "The most exciting thing about my research is to create new molecules and new
      concepts. When I was eighteen I wanted to be an industrial chemist. .." This and
      more about Koop Lammertsma can be found on page 4670.

PMID- 19408273
TI  - An efficient method based on the photothermal effect for the release of molecules
      from metal nanoparticle surfaces.
AB  - Please release me: The heat generated when metal nanoparticles absorb light
      results in a significant increase in the temperature of the environment around
      the particles and is used to selectively break bonds within a molecular system
      anchored to the nanoparticle surface (see picture). This process represents an
      advantageous and more universal method to deliver chemicals locally, while
      avoiding excessive tissue damage.

PMID- 19408274
TI  - All-in-one target-cell-specific magnetic nanoparticles for simultaneous molecular
      imaging and siRNA delivery.
AB  - Cancer-cell-targeted gene silencing was observed with a magnetic-nanoparticle
      platform (MEIO, magnetism-engineered iron oxide) on which a fluorescent dye,
      siRNA, and a RGD-peptide targeting moiety were attached (see picture). The
      different functionalities enable the macroscopic (magnetic resonance) and
      microscopic (fluorescence) imaging of target cells. This system may be suitable
      for concurrent diagnostic and therapeutic applications.

PMID- 19408275
TI  - Analysis of underivatized oligosaccharides by liquid chromatography/electrospray
      ionization tandem mass spectrometry with post-column addition of formic acid.
AB  - Underivatized oligosaccharides were analyzed by electrospray ionization (ESI)
      using a linear ion trap mass spectrometer in the negative ion mode with post
      column addition of an aqueous solution of formic acid. Under these conditions all
      oligosaccharides showed the presence of the corresponding formate adduct [M +
      HCOO](-) with high intensity and easy subsequent low-energy collision-induced
      dissociation (CID) fragmentation using successive MS(n) experiments. A careful
      examination of the mass spectra obtained from these MS(n) experiments pointed out
      some significant differences useful to identify and quantify the single
      components in mixtures of coeluted disaccharides. This new sensitive and rapid
      method was successfully applied to the quantification of oligosaccharides in some
      juices minimizing sample handling.

PMID- 19408276
TI  - A retention-time-shift-tolerant background subtraction and noise reduction
      algorithm (BgS-NoRA) for extraction of drug metabolites in liquid
      chromatography/mass spectrometry data from biological matrices.
AB  - A retention-time-shift-tolerant background subtraction and noise reduction
      algorithm (BgS-NoRA) is implemented using the statistical programming language R
      to remove non-drug-related ion signals from accurate mass liquid
      chromatography/mass spectrometry (LC/MS) data. The background-subtraction part of
      the algorithm is similar to a previously published procedure (Zhang H and Yang Y.
      J. Mass Spectrom. 2008, 43: 1181-1190). The noise reduction algorithm (NoRA) is
      an add-on feature to help further clean up the residual matrix ion noises after
      background subtraction. It functions by removing ion signals that are not
      consistent across many adjacent scans. The effectiveness of BgS-NoRA was examined
      in biological matrices by spiking blank plasma extract, bile and urine with
      diclofenac and ibuprofen that have been pre-metabolized by microsomal incubation.
      Efficient removal of background ions permitted the detection of drug-related ions
      in in vivo samples (plasma, bile, urine and feces) obtained from rats orally
      dosed with (14)C-loratadine with minimal interference. Results from these
      experiments demonstrate that BgS-NoRA is more effective in removing analyte
      unrelated ions than background subtraction alone. NoRA is shown to be
      particularly effective in the early retention region for urine samples and middle
      retention region for bile samples, where the matrix ion signals still dominate
      the total ion chromatograms (TICs) after background subtraction. In most cases,
      the TICs after BgS-NoRA are in excellent qualitative correlation to the
      radiochromatograms. BgS-NoRA will be a very useful tool in metabolite detection
      and identification work, especially in first-in-human (FIH) studies and multiple
      dose toxicology studies where non-radio-labeled drugs are administered. Data from
      these types of studies are critical to meet the latest FDA guidance on Metabolite
      in Safety Testing (MIST).

PMID- 19408277
TI  - The subspace iteration method in protein normal mode analysis.
AB  - Normal mode analysis plays an important role in relating the conformational
      dynamics of proteins to their biological function. The subspace iteration method
      is a numerical procedure for normal mode analysis that has enjoyed widespread
      success in the structural mechanics community due to its numerical stability and
      computational efficiency in calculating the lowest normal modes of large systems.
      Here, we apply the subspace iteration method to proteins to demonstrate its
      advantageous properties in this area of computational protein science. An
      effective algorithm for choosing the number of iteration vectors in the method is
      established, offering a considerable improvement over the original
      implementation. In the present application, computational time scales linearly
      with the number of normal modes computed. Additionally, the method lends itself
      naturally to normal mode analyses of multiple neighboring macromolecular
      conformations, as demonstrated in a conformational change pathway analysis of
      adenylate kinase. These properties, together with its computational robustness
      and intrinsic scalability to multiple processors, render the subspace iteration
      method an effective and reliable computational approach to protein normal mode
      analysis.

PMID- 19408279
TI  - A computational study of photochemical isomerization reactions of thiophenes.
AB  - The mechanisms of the photochemical isomerization reactions were investigated
      theoretically using three model systems; 2-methylthiophene, 2-cyanothiophene, and
      2-phenylthiophene. The CASSCF (10-electron/eight-orbital active space) and MP2
      CAS methods were employed with the 6-311(d) basis set. Three mechanisms, i.e.,
      the internal cyclization-isomerization route (path A), the zwitterion-tricyclic
      route (path B), and the direct route (path C), have been used to explore the real
      photochemical reaction mechanism of these three model molecules. The structures
      of the conical intersections, which play a key role in such phototranspositions,
      were obtained. The intermediates and transition structures of the ground states
      were also calculated to assist in providing a qualitative explanation of the
      reaction pathways. Our model investigations suggest that the preferred reaction
      route is as follows: reactant --> Franck-Condon region --> conical intersection -
      > photoproduct. In particular, the conical intersection mechanism described in
      this work gives a better explanation than either the previously proposed internal
      cyclization-isomerization (path A) or the zwitterion-tricyclic pathway (path B)
      mechanisms, and is supported by the experimental observations. The results
      obtained allow a number of predictions to be made.

PMID- 19408278
TI  - Theoretical study of the prion protein based on the fragment molecular orbital
      method.
AB  - We performed fragment molecular orbital (FMO) calculations to examine the
      molecular interactions between the prion protein (PrP) and GN8, which is a
      potential curative agent for prion diseases. This study has the following novel
      aspects: we introduced the counterpoise method into the FMO scheme to eliminate
      the basis set superposition error and examined the influence of geometrical
      fluctuation on the interaction energies, thereby enabling rigorous analysis of
      the molecular interaction between PrP and GN8. This analysis could provide
      information on key amino acid residues of PrP as well as key units of GN8
      involved in the molecular interaction between the two molecules. The present FMO
      calculations were performed using an original program developed in our
      laboratory, called "Parallelized ab initio calculation system based on FMO
      (PAICS)".

PMID- 19408280
TI  - Efficient extraction of free energy profiles from nonequilibrium experiments.
AB  - Hummer and Szabo recently presented a method based on the Jarzynski equality to
      calculate Helmholtz free energy profiles from nonequilibrium pathways obtained in
      simulations or experiments. In their approach, the free energy is reconstructed
      from weighted histograms. Here, we give a systematic derivation of the optimum
      weight, which--in principle--minimizes the statistical errors in the resulting
      free energy profiles. We then compare this optimum weight to Hummer and Szabo's
      original weight and several others by means of simulations of two one-dimensional
      models, for which the free energy profile is analytically known. In addition, we
      carry out simulations of a deca-alanine molecule pulled by a harmonic trap to
      assess the efficiency of the weights in a more realistic situation. In all cases,
      the weight of Hummer and Szabo performs very well leading to errors approximately
      equal to those obtained with a simplified version of the optimum weight. The
      performance of the optimum weight itself is unsatisfying due to statistical
      errors arising in the weight calculation.

PMID- 19408281
TI  - Tuning aromaticity in trigonal alkaline earth metal clusters and their alkali
      metal salts.
AB  - In this work, we analyze the geometry and electronic structure of the
      [X(n)M(3)](n-2) species (M = Be, Mg, and Ca; X = Li, Na, and K; n = 0, 1, and 2),
      with special emphasis on the electron delocalization properties and aromaticity
      of the cyclo-[M(3)](2-) unit. The cyclo-[M(3)](2-) ring is held together through
      a three-center two-electron bond of sigma-character. Interestingly, the
      interaction of these small clusters with alkali metals stabilizes the cyclo
      [M(3)](2-) ring and leads to a change from sigma-aromaticity in the bound state
      of the cyclo-[M(3)](2-) to pi-aromaticity in the XM(3) (-) and X(2)M(3) metallic
      clusters. Our results also show that the aromaticity of the cyclo-[M(3)](2-) unit
      in the X(2)M(3) metallic clusters depends on the nature of X and M. Moreover, we
      explored the possibility for tuning the aromaticity by simply moving X
      perpendicularly to the center of the M(3) ring. The Na(2)Mg(3), Li(2)Mg(3), and
      X(2)Ca(3) clusters undergo drastic aromaticity alterations when changing the
      distance from X to the center of the M(3) ring, whereas X(2)Be(3) and K(2)Mg(3)
      keep its aromaticity relatively constant along this process.

PMID- 19408282
TI  - Paired orbitals for different spins equations.
AB  - Eigenvalue-type equations for Lowdin-Amos-Hall spin-paired (corresponding)
      orbitals are developed to provide an alternative to the standard spin-polarized
      Hartree-Fock or Kohn-Sham equations in dealing with broken-symmetry (BS) states.
      To derive paired orbitals for different spins (PODS) equations there has been
      applied Adams-Gilbert "localizing" operator approach. The PODS equations contain
      different operators for different spins the eigenvectors of which are paired
      orbitals associated with the same eigenvalue for each pair. Preliminary
      applications to simple systems show viability of this approach. Although the
      spectrum of possible applications of the PODS equations seems to be quite wide,
      they would be especially useful for obtaining and analyzing the S(z) = 0 BS
      solutions for the systems with antiferromagnetic structure.

PMID- 19408283
TI  - Structural and dynamical properties of the V(3+) ion in dilute aqueous solution:
      An ab initio QM/MM molecular dynamics simulation.
AB  - A hybrid ab initio QM/MM molecular dynamics simulation at the Hartree-Fock level
      has been performed to investigate structural and dynamical parameters of the
      V(3+) ion in dilute aqueous solution. A distorted octahedral structure with the
      average V(3+)-O distance of 1.99 A is evaluated from the QM/MM simulation, which
      is in good agreement with the X-ray data. Several structural parameters such as
      angular distribution functions, theta- and tilt-angle distributions have been
      determined to obtain the full description of the hydration structure of the
      hydrated V(3+). The Jahn-Teller distortions of the V(3+) ion are pronounced in
      the QM/MM simulation. The mean residence time of 14.5 ps is estimated for the
      ligand exchange processes in the second hydration shell.

PMID- 19408284
TI  - Phenotype and chondrogenic differentiation of mesenchymal cells from adipose
      tissue of different species.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating
      into several mesoderm lineages. They have been isolated from different tissues,
      such as bone marrow, adult peripheral blood, umbilical cord blood, and adipose
      tissue. The aim of this study was to analyze the differences in proliferation and
      phenotype of adipose tissue-derived MSCs from three different species, and to
      evaluate their capacity to differentiate into chondrocytes in vitro. A
      comparative study of cultured human, rabbit, and sheep mesenchymal cells from
      adipose tissue was carried out, and the main morphological parameters,
      proliferative activity, and expression of surface markers were characterized.
      Proliferation and flow cytometry data showed species-related differences between
      animal and human MSCs. Histological staining suggested that rabbit and sheep
      mesenchymal cells were able to differentiate into chondrocytic lineages. Human
      mesenchymal cells, though they could also differentiate, accomplished it with
      more difficulty than animal MSCs. These results could help to explain the
      differences in the chondrogenic capacity of sheep and rabbit MSCs when they are
      used as animal models compared to human mesenchymal cells in a clinical assay.

PMID- 19408285
TI  - Medial knee joint loading increases in those who respond to hyaluronan injection
      for medial knee osteoarthritis.
AB  - Knee osteoarthritis (OA) is a cause of decline in function and the medial
      compartment is often affected. Intraarticular injection of hyaluronic acid (HA)
      is indicated as a symptom modifying treatment with at least 6 months passing
      between consecutive injection series. The effects of HA injection on gait
      variables have not been extensively examined. Therefore, our objective was to
      investigate the effects of HA injection on gait in people with medial knee OA.
      Twenty-seven subjects were included; each was tested prior to treatment
      (baseline), no later than 3 weeks following the last injection (post-HA), and
      again 5 months after treatment ended (follow-up). Responder criteria were defined
      to identify responders and non-responders. Subjects underwent 3D gait analysis,
      muscle activity was sampled, and co-contraction indices were calculated.
      Responders experienced increased peak knee adduction moments post-HA, whereas non
      responders did not. Improved self-report scores were associated with increased
      knee adduction moments and increased medial co-contraction. Pain relief may
      result in higher loading onto the already vulnerable medial compartment due to
      changes in lower limb mechanics and muscle activation patterns. Eventually this
      may result in a more rapid progression of joint deterioration.

PMID- 19408286
TI  - The gestational timing of pregnancy loss: adaptive strategy?
AB  - This commentary links early pregnancy milestones (rescue of the corpus luteum,
      the luteal-placental shift, and blocking of the spiral arteries) with the pattern
      of gestation-specific pregnancy loss in humans. The objective is to describe the
      pattern and present an adaptive hypothesis: that high first trimester pregnancy
      loss results from selection to reduce the risk of maternal morbidity and
      mortality associated with human delivery. Specific questions within the broad
      framework of this hypothesis can be addressed with research in comparative
      physiology and endocrinology.

PMID- 19408287
TI  - Distribution and abundance of sacred monkeys in Igboland, southern Nigeria.
AB  - Although primates are hunted on a global scale, some species are protected
      against harassment and killing by taboos or religious doctrines. Sites where the
      killing of sacred monkeys or the destruction of sacred groves is forbidden may be
      integral to the conservation of certain species. In 2004, as part of a
      distribution survey of Sclater's guenon (Cercopithecus sclateri) in southern
      Nigeria, we investigated reports of sacred monkeys in the Igbo-speaking region of
      Nigeria. We confirmed nine new sites where primates are protected as sacred: four
      with tantalus monkeys (Chlorocebus tantalus) and five with mona monkeys
      (Cercopithecus mona). During 2004-2006, we visited two communities (Akpugoeze and
      Lagwa) previously known to harbor sacred populations of Ce. sclateri to estimate
      population abundance and trends. We directly counted all groups and compared our
      estimates with previous counts when available. We also estimated the size of
      sacred groves and compared these with grove sizes reported in the literature. The
      mean size of the sacred groves in Akpugoeze (2.06 ha, n = 10) was similar to
      others in Africa south of the Sahel, but larger than the average grove in Lagwa
      (0.49 ha, n = 15). We estimated a total population of 124 Sclater's monkeys in 15
      groups in Lagwa and 193 monkeys in 20 groups in Akpugoeze. The Akpugoeze
      population was relatively stable over two decades, although the proportion of
      infants declined, and the number of groups increased. As Sclater's monkey does
      not occur in any official protected areas, sacred populations are important to
      the species' long-term conservation. Despite the monkeys' destruction of human
      crops, most local people still adhere to the custom of not killing monkeys. These
      sites represent ideal locations in which to study the ecology of Sclater's monkey
      and human-wildlife interactions.

PMID- 19408289
TI  - Local recurrences and second primary tumors from squamous cell carcinoma of the
      oral cavity: a retrospective analytic study of 500 patients.
AB  - BACKGROUND: The purpose of this study was to evaluate the incidence of local
      recurrences (LRs) and second primary tumors (SPTs) from squamous cell carcinoma
      (SCC) of the oral cavity primarily treated with surgery and to further study
      their relationship with several primary tumor clinical and pathological features.
      METHODS: Five hundred of 522 patients with SCC of the oral cavity primarily
      treated with surgery were retrospectively analyzed for the appearance of LRs and
      SPTs within the oral cavity. All patients with SPTs fulfilled the Warren & Gates
      criteria. Several clinical features were analyzed. Histological study included
      TNM classification, tumor size, tumor thickness, surgical margins, perineural
      infiltration, peritumoral inflammation, and bone involvement. In the univariant
      analysis, the possible association between different clinical and pathological
      features and the presence of LRs or SPTs was analyzed by means of the chi-square
      test for categorical data and the Student's t test for parametric data. The
      appearance of LRs and SPTs was also studied by binary logistic regression as time
      dependant phenomena, in the univariant analysis. Logistic regression was also
      used for the multivariant analysis between the selected variables. The Kaplan
      Meier method was used to estimate the probability of SPT- or LR-free survival.
      RESULTS: The mean duration of the follow-up period was 52.27 +/- 49.52 months. At
      the end of this time, 53.82% of the patients were alive without evidence of
      disease, whereas 31.48% had specifically died of disease. Twenty-eight (5.6%)
      patients developed an SPT within the oral cavity, whereas 95 (19%) patients
      developed an LR during the whole follow-up period. The 5-year disease-specific
      survival rate for the whole series was 67.2%, in contrast to 34.9% in the group
      of patients with SPT and/or LR. In relation to the univariant analysis, T
      classification, TNM staging, pT classification, surgical margins, bone
      involvement, and postoperative radiotherapy (RT) were found to be predictive for
      LR. In relation to the multivariant analysis, only postoperative RT and bone
      involvement were predictive for the development of LR. CONCLUSION: The
      identification of preoperative and postoperative clinical and pathological
      features that prelude a higher risk for the appearance of LRs and/or SPTs may be
      of potential interest in determining which patients should benefit of a closer
      regular follow-up. When considering together the whole clinical and pathological
      features, only postoperative RT and bone involvement were predictive for the
      development of LRs. Because of the poor survival rate of the affected patients,
      we strongly recommend aggressive surgical treatment following the appearance of
      an SPT or LR.

PMID- 19408288
TI  - Comparison of two prognostic scores for patients with parotid carcinoma.
AB  - BACKGROUND: Salivary glands present a wide diversity in histopathologic types and
      biologic behaviors, thus complicating the search for prognostic factors. METHODS:
      We compared 2 prognostic scores that were previously published for patients with
      parotid carcinoma in a retrospective series of 175 patients treated in a single
      institution. RESULTS: Cox multivariate analysis indicated clinical skin invasion,
      facial nerve function, and perineural growth as the most significant recurrent
      disease-related prognostic factors. According to the Vander Poorten score, 148
      patients were divided into 4 groups, with the 5-year disease-free survival of
      76%, 81%, 69%, and 35%, respectively. In the Carrillo's score, the patients were
      divided into 3 groups: low-risk, intermediate-risk, and high-risk, with the 5
      year disease-free survival of 84%, 73%, and 34%, respectively. CONCLUSION:
      Carrillo's score showed more distinct survival curves, and determination of
      groups with a more favorable prognosis was difficult for both scores. Therefore,
      both scores were not totally reproducible for our group of patients.

PMID- 19408290
TI  - Analysis of free flap viability based on recipient vein selection.
AB  - BACKGROUND: Venous anastomotic failure is the primary reason for microvascular
      free tissue transfer failure. Donor and recipient veins can be oriented in the
      same longitudinal axis (end-to-end anastomosis), or the donor vein can be
      anastomosed to the internal jugular vein in an end-to-side configuration. No
      consensus on the optimal anastomosis configuration exists. We sought to evaluate
      whether type of venous anastomosis impacts flap survival rate. METHODS: Data were
      collected on all patients undergoing microvascular free flap reconstruction of
      head and neck defects at the University of Washington between August 1993 and
      April 2007. Flaps with a single venous anastomosis were analyzed. Flaps were
      stratified into those with end-to-end and end-to-side anastomoses. Survival rates
      were compared between groups using bivariate and multivariate techniques.
      RESULTS: Inclusion criteria were met by 786 free flaps; 87% performed in an end
      to-end and 13% in an end-to-side configuration. Flap re-exploration and failure
      rate were 4.3% and 1.1%, respectively. In multivariate analysis, there was no
      difference in odds of flap re-exploration (OR .70, 95% CI .23-2.18) or flap
      failure whether or not an end-to-end or end-to-side anastomosis was performed (OR
      2.09, 95% CI .38-11.5). CONCLUSIONS: In this large cohort of patients, we found
      no difference in the odds of flap re-exploration or failure based on venous
      anastomotic configuration. Reconstructive surgeons should have both anastomotic
      techniques in their repertoire to optimize the success of every flap.

PMID- 19408291
TI  - Prospective randomized study of selective neck dissection versus observation for
      N0 neck of early tongue carcinoma.
AB  - BACKGROUND: There are controversies on the benefits of elective neck dissection
      (END) for oral tongue carcinoma. METHOD: This is a prospective randomized study
      of elective selective I, II, III neck dissection versus observation for N0 neck
      of stage I to II oral tongue carcinoma. There were 35 patients on the observation
      arm and 36 patients on the END arm. The main outcome assessment parameters are
      node-related mortality and disease-specific survival rate. RESULTS: There were 11
      patients in the observed arm and 2 patients in the END arm who developed nodal
      recurrence alone without associated local or distant recurrence. All 13 patients
      were salvaged, and no patient died of nodal recurrence. The 5-year disease
      specific survival rate was 87% for the observation arm and was 89% for the END
      arm; the 2% difference was not significant. CONCLUSION: Observation may be an
      acceptable alternative to END if strict adherence to a cancer surveillance
      protocol is followed.

PMID- 19408292
TI  - Predictors of outcome for advanced-stage supraglottic laryngeal cancer.
AB  - BACKGROUND: The objective of this study was to report our experience in the
      management of patients with advanced-stage supraglottic laryngeal carcinoma and
      to identify factors predictive of outcome. METHODS: In total, 181 patients with
      advanced-stage supraglottic laryngeal carcinoma were treated at Memorial Sloan
      Kettering Cancer Center between 1984 and 1998. Sixty-nine (38%) patients were
      treated by surgery +/- postoperative radiotherapy (SRT), 93 (52%) by
      chemoradiotherapy (CTRT), and 19 (10%) by radiotherapy alone (RT). Survival
      outcomes were calculated using the Kaplan-Meier method. Predictors of outcome
      were identified using multivariate analysis. RESULTS: The-5 year overall survival
      (OS) and disease-specific survival (DSS) were 53% and 71%, respectively. Patients
      treated with SRT and CTRT had comparable outcomes. The main independent
      predictors of OS and DSS were age greater than 60 years and stage of the neck at
      presentation. CONCLUSION: Regardless of index treatment, age over 60 years and
      clinical stage of the neck at presentation were the main independent predictors
      of OS and DSS.

PMID- 19408294
TI  - In vivo, in vitro and in silico methods for small molecule transfer across the
      BBB.
AB  - The inability of molecules to permeate the BBB is a significant source of
      attrition in Central Nervous System (CNS) drug discovery. Given the increasing
      medical drivers for new and improved CNS drugs, small molecule transfer across
      the BBB is attracting a heightened awareness within pharmaceutical industry and
      medical fields. In order to assess the potential for small CNS molecules to
      permeate the BBB, a variety of methods and models, from in silico to in vivo
      going through in vitro models are developed as predictive tools in drug
      discovery. This review gives a comprehensive overview of different approaches
      currently considered in drug discovery to circumvent the lack of small molecule
      transfer through the BBB, together with their inherent advantages and
      disadvantages. Particularly, special attention is drawn to in silico models, with
      a detailed and contemporary point of view on prediction tools and guidelines for
      rational design.

PMID- 19408293
TI  - Absorption of polyethylene glycol (PEG) polymers: the effect of PEG size on
      permeability.
AB  - Polyethylene glycol (PEG) polymers are large amphiphilic molecules that are
      highly hydrated in solution. To explore the permeability properties of different
      sized PEG polymers across epithelial membranes in vivo, we examined the
      absorption of fluorescently labeled PEG conjugates sized 0.55-20 kDa from the
      lung, since this system provides a reservoir that limits rapid diffusion of
      molecules away from the site of delivery and enables permeability over longer
      times to be examined. Following intratracheal delivery in rats, the PEG polymers
      underwent absorption with first-order kinetics described by single exponential
      decay curves. PEG size produced a marked influence on the rate of uptake from the
      lung, with half-lives ranging from 2.4 to 13 h, although above a size of 5 kDa,
      no further change in rate was observed. PEG size likewise affected retention in
      alveolar macrophages and in lung tissue; whereas smaller PEG sizes (<2 kDa) were
      effectively cleared within 48 h, larger PEG sizes (>5 kDa) remained in lung cells
      and tissue for up to 7 days. These data demonstrate that PEG polymers can be
      absorbed across epithelial membranes and that PEG size plays a dominant role in
      controlling the rate and mechanism of absorption.

PMID- 19408295
TI  - The role of mucoadhesion of trimethyl chitosan and PEGylated trimethyl chitosan
      nanocomplexes in insulin uptake.
AB  - The aim of this work was to investigate the role of mucoadhesion in the insulin
      uptake of nanocomplexes (NC) based of trimethyl chitosan (TMC) and poly(ethylene
      glycol) (PEG)-graft-TMC copolymers. Self-assembled insulin NC were prepared by
      polyelectrolyte complexation. The effects of PEGylation and positive charge
      density on mucoadhesion were assessed using a mucin assay and mucus-secreting
      HT29-MTX-E12 (E12) monolayers. The behaviors of corresponding insulin NC after
      adhesion to E12 were also established. All PEGylated TMC copolymers showed
      significantly higher levels of adhesion to mucus than unmodified TMC. The
      copolymer composed of 298 PEG chains per TMC macromolecules exhibited the highest
      level of mucoadhesion, being 3.4 times higher than TMC. The higher mucoadhesive
      properties of PEGylated TMC copolymers resulted from the synergistic effects of
      interpenetration of PEG chains into the mucus and electrostatic interaction
      between positive charged TMC and anionic glycoproteins present in the mucus
      layer. Compared to TMC, insulin NC based on PEGylated TMC copolymers demonstrated
      no evidence of insulin uptake improvement due to complete release of insulin from
      NC after adhering to mucus. CLSM revealed the localization of TMC and its
      corresponding insulin NC at cell surface membranes of E12.

PMID- 19408297
TI  - Computational protein design as a tool for fold recognition.
AB  - Computationally designed protein sequences have been proposed as a basis to
      perform fold recognition and homology searching. To investigate this possibility,
      an automated procedure is used to completely redesign 24 SH3 proteins and 22 SH2
      proteins. We use the experimental backbone coordinates as fixed templates in the
      folded state and a molecular mechanics model to compute the pairwise interaction
      energies between all sidechain types and conformations. Energy calculations are
      done with the Proteins@Home volunteer computing platform. A heuristic algorithm
      is then used to scan the sequence and conformational space for optimal solutions.
      We produced 200,000-450,000 sequences for each backbone template. The designed
      sequences ressemble moderately-distant, natural homologues of the initial
      templates, according to their identity scores and their similarity with respect
      to the Pfam sets of SH2 and SH3 domains. Standard homology detection tools
      document their native-like character: the Conserved Domain Database recognizes
      61% (52%) of our low-energy sequences as SH3 (SH2) domains; the SUPERFAMILY,
      Hidden-Markov Model library recognizes 81% (84%). Conversely, position specific
      scoring matrices (PSSMs) derived from our designed sequences can be used to
      detect natural homologues in sequence databases. Within SwissProt, a set of
      natural SH3 PSSMs detects 772 SH3 domains, for example; our designed PSSMs detect
      67% of these, plus one additional sequence and two false positives. If six amino
      acids involved in substrate binding (a selective pressure not accounted for in
      our design) are reset to their experimental types, then 77% of the experimental
      SH3 domains are detected. Results for the SH2 domains are similar. Several
      directions to improve the method further are discussed.

PMID- 19408296
TI  - Thermodynamic and structural aspects of sulfonamide crystals and solutions.
AB  - The crystal structures of three sulfonamides with the general structure 4-NH(2)
      C(6)H(4)-SO(2)NH-C(6)H(4/3)-R (R = 4-Et; 4-OMe; 5-Cl-2-Me) have been determined
      by X-ray diffraction. On the basis of our previous data and the results obtained
      a comparative analysis of crystal properties was performed: molecular
      conformational states, packing architecture, and hydrogen bond networks using
      graph set notations. The thermodynamic aspects of the sulfonamide sublimation
      process have been studied by investigating the temperature dependence of vapor
      pressure using the transpiration method. A regression equation was derived
      describing the correlation between sublimation entropy terms and crystal density
      data calculated from X-ray diffraction results. Also correlations between
      sublimation Gibbs energies and melting points, on the one hand, and between
      sublimation enthalpies and fusion enthalpies at 298 K, on the other hand, were
      found. These dependencies give the opportunity to predict sublimation
      thermodynamic parameters by simple thermo-physical experiments (fusion
      characteristics). Solubility processes of the compounds in water, n-hexane, and n
      octanol (as phases modeling various drug delivery pathways and different types of
      membranes) were investigated and corresponding thermodynamic functions were
      calculated as well. Thermodynamic characteristics of sulfonamide solvation were
      evaluated. For compounds with similar structures processes of transfer from one
      solvent to another one were studied by a diagram method combined with analysis of
      enthalpic and entropic terms. Distinguishing between enthalpy and entropy, as is
      possible through the present approach, leads to the insight that the contribution
      of these terms is different for different molecules (entropy- or enthalpy
      determined). Thus, in contrast to interpretation of only the Gibbs energy of
      transfer, being extensively used for pharmaceuticals in the form of the partition
      coefficient (log P), the analysis of thermodynamic functions of the transfer
      process provides additional mechanistic information. This may be important for
      further evaluation of the physiological distribution of drug molecules and may
      provide a better understanding of biopharmaceutical properties of drugs.

PMID- 19408298
TI  - Structural bioinformatics mutation analysis reveals genotype-phenotype
      correlations in von Hippel-Lindau disease and suggests molecular mechanisms of
      tumorigenesis.
AB  - Mutations in the VHL gene lead to von Hippel-Lindau (VHL) disease, a clinically
      heterogeneous cancer syndrome. Here, we use software and database tools to
      understand and predict the phenotypes associated with missense mutations in the
      VHL gene product, pVHL. The protein product pVHL is known to interact with
      elongin B, elongin C, and the HIF substrate. By analyzing known and predicted
      interaction sites and predictions of thermodynamic stability change upon
      mutation, we generate new hypotheses regarding the molecular etiology of renal
      cell carcinoma (RCC) and pheochromocytoma (PCC) in VHL disease. We find that the
      molecular causes of RCC and PCC appear to be decoupled. RCC may arise through two
      distinct mechanisms: disruption of HIF interactions or binding at the elongin B
      interface. PCC is triggered by mutations which disrupt interactions at the
      elongin C binding site. These findings have important implications for VHL
      disease and for nonfamilial RCC, because most cases of clear cell RCC are linked
      with VHL inactivation. Additionally, predicting effects of genetic variation will
      be critical as genetic sequencing accelerates; the analytical strategy presented
      here may elucidate other systems as further data on genetic variation become
      available.

PMID- 19408299
TI  - Nonadditive effects of mixed crowding on protein stability.
AB  - The crowded environments inside cells can have significant effects on the folding
      stability and other biophysical properties of proteins. In this study on how
      macromolecular crowding affects protein folding, we took a significant step
      toward realistically mimicking intracellular environments by using a mixture of
      two crowding agents, Ficoll and dextran. We found that the mixed crowding exerts
      a greater stabilizing effect than the sum of the two individual crowding agents.
      Therefore, the composition of crowders, not just the total concentration, has a
      significant influence on the effects of crowding on protein folding. Since the
      composition of intracellular macromolecules varies within the lifetime of a cell,
      our finding may provide an explanation for age being an important risk factor for
      protein aggregation-related diseases such as Alzheimer's disease and Parkinson's
      disease.

PMID- 19408301
TI  - Automated scaffold selection for enzyme design.
AB  - A major goal of computational protein design is the construction of novel
      functions on existing protein scaffolds. There the first question is which
      scaffold is suitable for a specific reaction. Given a set of catalytic residues
      and their spatial arrangement, one wants to identify a protein scaffold that can
      host this active site. Here, we present an algorithm called ScaffoldSelection
      that is able to rapidly search large sets of protein structures for potential
      attachment sites of an enzymatic motif. The method consists of two steps; it
      first identifies pairs of backbone positions in pocket-like regions. Then, it
      combines these to complete attachment sites using a graph theoretical approach.
      Identified matches are assessed for their ability to accommodate the substrate or
      transition state. A representative set of structures from the Protein Data Bank (
      approximately 3500) was searched for backbone geometries that support the
      catalytic residues for 12 chemical reactions. Recapitulation of native active
      site geometries is used as a benchmark for the performance of the program. The
      native motif is identified in all 12 test cases, ranking it in the top percentile
      in 5 out of 12. The algorithm is fast and efficient, although dependent on the
      complexity of the motif. Comparisons to other methods show that ScaffoldSelection
      performs equally well in terms of accuracy and far better in terms of speed.
      Thus, ScaffoldSelection will aid future computational protein design experiments
      by preselecting protein scaffolds that are suitable for a specific reaction type
      and the introduction of a predefined amino acid motif.

PMID- 19408300
TI  - A new natural angelica polysaccharide based colon-specific drug delivery system.
AB  - Colon-specific drug delivery systems are clinically necessary to treat colon
      diseases locally while minimizing systemic side effects. In this study, we
      extracted angelica polysaccharide from fresh roots of Angelica sinensis Diels and
      analyzed the monosaccharide components. With succinate as a cross-linker and
      angelica polysaccharide as a drug carrier, a dexamethasone-polysaccharide
      conjugate was synthesized. The amount of dexamethasone (Dex) loaded in the
      dexamethasone-polysaccharide conjugate was 14.13/100 mg. The newly synthesized
      dexamethasone-polysaccharide conjugate was found to greatly reduce systemic
      absorption of Dex and effectively deliver Dex to the large intestine. When
      dexamethasone-polysaccharide conjugate was used to treat TNBS-induced ulcerative
      colitis in rats by gavage, the ulcerative area of the colon and the colonic
      myeloperoxidase (MPO) activity was reduced in a dose-dependent manner. There was
      no effects on spleen weight, thymus weight, or peripheral blood lymphocyte count
      (0.25 micromol kg(-1) day(-1)). These results indicate that the dexamethasone
      polysaccharide conjugate has a therapeutic effect on TNBS-induced ulcerative
      colitis in rats, while simultaneously reducing the systemic immunosuppression
      caused by Dex. Thus, the angelica polysaccharide was a promising colon-specific
      drug carrier, and the new dexamethasone-polysaccharide conjugate may yield a
      potential drug for the treatment of human inflammatory bowel disease.

PMID- 19408302
TI  - False negative fecal occult blood tests due to delayed sample return in
      colorectal cancer screening.
AB  - Delayed return of immunochemical fecal occult blood test (iFOBT) samples to a
      laboratory might cause false negatives because of hemoglobin degradation.
      Quantitative iFOBT's became increasingly more accepted in colorectal cancer
      screening. Therefore, we studied the effects of delay between sampling and
      laboratory delivery on iFOBT performance. IFOBT positivity (>or=50 ng/ml
      hemoglobin) in colorectal cancer screening participants without delay between
      sampling and laboratory delivery (<5 days), was compared with positivity in
      participants with >or=5 and >or=7 days delay. Additionally, positive tests were
      stored at room temperature and retested 5 times within 10-14 days. The sampling
      date was reported by 61% (n = 3,767) of the participants: in 19% delay was >or=5
      days and in 5% >or=7 days. Compared with no-delay, the adenoma detection rate was
      already significantly decreased after >or=5 days delay (OR 0.6; 95%CI 0.4-0.9).
      We retested iFOBT samples of 170 positives of which 139 (82%) had a colonoscopy:
      45 (32%) had advanced adenomas (not colorectal cancer) and 8 (6%) had colorectal
      cancer. Mean daily fecal hemoglobin decrease was 29 ng/ml (S.D. 38 and median 11
      ng/ml). In patients with advanced adenomas, hemoglobin in the sample was <50
      ng/ml in 5 (11%) 2-3 days after the initial test and in 16 (36%) after 10-14
      days. Seven days after the initial test, 2 (25%) colorectal cancer patients
      became false negative. Both had stage I colorectal cancer and initial values
      below 100 ng/ml, where the average for stage I is 532 ng/ml. Delay in sample
      return increased false negative immunochemical FOBT's. Mainly precursor lesions,
      but also colorectal cancer, will be missed due to delayed sample return.

PMID- 19408304
TI  - Functional analysis of the -2548G/A leptin gene polymorphism in breast cancer
      cells.
AB  - Leptin is overexpressed in human breast tumors and is produced by breast cancer
      cells in response to obesity-related stimuli. The leptin promoter polymorphism
      Lep-2548G/A can be associated with increased leptin secretion by adipocytes and
      elevated cancer risk. However, molecular mechanisms underlying the link between
      Lep-2548G/A and breast cancer have never been addressed. Lep-2548G/A is proximal
      to a binding site for the transcriptional factor Sp1. Furthermore nucleolin, a
      transcriptional repressor, can bind Sp1 or its consensus site. Consequently, we
      focused on the impact of Lep-2548G/A on Sp1- and nucleolin-dependent leptin
      transcription in breast cancer cells. The Lep-2548G/A was identified in a
      homozygous conformation in BT-474 and SK-BR-3 breast cancer cells, in a
      heterozygous conformation in MDA-MB-231 cells, and a wild-type Lep-2548G/G
      sequence was present in MCF-7 and ZR-75-1 cells. The occurrence of Lep-2548A/A
      and Lep-2548G/A coincided with high and intermediate leptin mRNA expression,
      respectively, while cells containing Lep-2548G/G expressed low leptin mRNA
      levels. We demonstrated that the existence of Lep-2548G/A improved efficient
      recruitment of Sp1 to DNA under insulin treatment, while Sp1 loading on DNA
      containing Lep-2548G/G was not insulin-dependent. In contrast, nucleolin binding
      to Lep-2548G/A was downregulated in response to insulin, while it was not
      regulated on Lep-2548G/G. The presence of Lep-2548G/A was studied in breast
      cancer epithelial cells by IHC and LCM. Interestingly, all 14 tumors expressing
      high leptin levels contained Lep-2548A/A. In conclusion, the occurrence of Lep
      2548G/A can enhance leptin expression in breast cancer cells via Sp1- and
      nucleolin-dependent mechanisms and possibly contribute to intratumoral leptin
      overexpression.

PMID- 19408303
TI  - CD4+ lymphocytes modulate prostate cancer progression in mice.
AB  - Chronic inflammation contributes to the development of prostate cancer in humans.
      Here, we show that male Apc(Min/+) mice also develop prostate carcinoma with
      increasing age, mimicking that seen in humans in their 5th or 6th decade of life.
      Proinflammatory cytokines were significantly linked with cancer and increasing
      age in our mouse model; however, prostate and bowel tissues lacked evidence of
      inflammatory cell infiltrates other than mast cells. Lymphocytes protected
      against cancer, and protection from prostate cancer resided in antiinflammatory
      CD4(+)CD25(+) regulatory (T(REG)) cells that downregulated inflammatory
      cytokines. Supplementation with syngeneic T(REG) cells collected from wild-type
      mice reduced the levels of interleukin (IL)-6 (p < 0.05) and IL-9 (p < 0.001) and
      lowered prostate cancer risk (p < 0.05). Depletion of CD25(+) cells in 2-month
      old animals increased the expression of IL-6 (p < 0.005) within prostate and
      increased the frequency of high-grade prostatic intraepithelial neoplasia (p <
      0.05) and microinvasive prostatic carcinoma (p < 0.05) in dorsolateral prostate.
      Depletion of CD25(+) cells in young animals also increased the frequency of
      intestinal cancer in Min mice. Taken together, chronically elevated
      proinflammatory cytokines promoted carcinoma in Apc(Min/+) mice. T(REG)
      lymphocytes downregulated inflammation-associated carcinogenic processes and
      contributed to immune and epithelial homeostasis.

PMID- 19408305
TI  - Downregulation of the c-MYC target gene, peroxiredoxin III, contributes to
      arsenic trioxide-induced apoptosis in acute promyelocytic leukemia.
AB  - Arsenic trioxide (ATO) induces differentiation and apoptosis in acute
      promyelocytic leukemia (APL). Several reports indicate that in APL cells
      apoptosis occurs mainly by a mechanism that involves the inhibition of
      glutathione peroxidase, one of the enzymes that regulates mitochondrial levels of
      H(2)O(2). Peroxiredoxin (Prx) III, a c-MYC target gene, is also a mitochondria
      specific H(2)O(2)-scavenger enzyme. We studied here the role of Prx III during
      ATO-induced apoptosis in APL-derived NB4 cells, since these cells express high
      levels of Prx III. The protein and mRNA levels of Prx III decreased during ATO
      induced apoptosis of NB4 cells. The downregulation of Prx III occurred before
      reactive oxygen species accumulation, reduction in the mitochondrial membrane
      potential and apoptosis. Depletion of Prx III enhanced mitochondrial-dependent
      apoptosis events. In contrast, overexpression of Prx III led to reduced levels of
      ATO-induced apoptosis. c-MYC was also downregulated in ATO-treated NB4 cells.
      Furthermore, depletion of c-MYC also reduced the Prx-III expression levels.
      Finally chromatin immunoprecipitation and luciferase reporter assays confirmed
      that downregulation of Prx-III was caused by the reduction of c-MYC levels during
      ATO-induced apoptosis of NB4 cells. These findings demonstrate a novel apoptotic
      response pathway whereby downregulation of Prx-III potentiates ATO-induced
      apoptosis in APL cells.

PMID- 19408306
TI  - A new pulsed electric field therapy for melanoma disrupts the tumor's blood
      supply and causes complete remission without recurrence.
AB  - We have discovered a new, ultrafast therapy for treating skin cancer that is
      extremely effective with a total electric field exposure time of only 180
      microsec. The application of 300 high-voltage (40 kV/cm), ultrashort (300 nsec)
      electrical pulses to murine melanomas in vivo triggers both necrosis and
      apoptosis, resulting in complete tumor remission within an average of 47 days in
      the 17 animals treated. None of these melanomas recurred during a 4-month period
      after the initial melanoma had disappeared. These pulses generate small, long
      lasting, rectifying nanopores in the plasma membrane of exposed cells, resulting
      in increased membrane permeability to small molecules and ions, as well as an
      increase in intracellular Ca(2+), DNA fragmentation, disruption of the tumor's
      blood supply and the initiation of apoptosis. Apoptosis was indicated by a 3-fold
      increase in Bad labeling and a 72% decrease in Bcl-2 labeling. In addition,
      microvessel density within the treated tumors fell by 93%. This new therapy
      utilizing nanosecond pulsed electric fields has the advantages of highly
      localized targeting of tumor cells and a total exposure time of only 180
      microsec. These pulses penetrate into the interior of every tumor cell and
      initiate DNA fragmentation and apoptosis while at the same time reducing blood
      flow to the tumor. This new physical tumor therapy is drug free, highly
      localized, uses low energy, has no significant side effects and results in very
      little scarring.

PMID- 19408308
TI  - Sulfobutyl ether-alkyl ether mixed cyclodextrin derivatives with enhanced
      inclusion ability.
AB  - The aim of this work was to study the complexation capability of new sulfobutyl
      ether-alkyl ether (SBE-AE-CD) mixed beta- and gamma-cyclodextrin derivatives with
      a series of structurally related steroids (6alpha-methylprednisolone,
      prednisolone, triamcinolone, D(-) norgestrel and hydrocortisone) and a number of
      dihydropyridine calcium channel blockers (nimodipine, nitrendipine, nifedipine)
      that traditionally interact poorly with other cyclodextrins (CDs). The effect of
      the total degree of substitution (TDS) and of the length of the alkyl side chain
      on binding capacity of these new modified CDs was evaluated as was their ability
      to induce red blood cell hemolysis. An attempt was made to correlate hemolysis to
      surface activity. Binding constants between the SBE-AE-CDs and selected molecules
      were determined by spectroscopic studies, and only in few cases by solubility
      studies. Hemolysis percentage was determined using citrated rabbit blood and
      citrated human blood with UV analysis. The surface activity was measured with a
      tensiometer. A significant improvement in the binding capacity between various
      substrates and the new SBE-AE-CDs was observed when compared to the SBE-CDs. The
      length of the alkyl chain and total degree of alkylation affected the binding
      with the relationship being complex. For most compounds, an intermediate degree
      of substitution appeared to be advantageous. The hemolysis studies showed that
      some of the derivatives may induce hemolysis and this correlated with higher
      surface activity for some but not all of the derivatives.

PMID- 19408309
TI  - A novel flow through diffusion cell for assessing drug transport across the
      buccal mucosa in vitro.
AB  - A novel flow through (FT) diffusion cell for assessing the permeability of
      compounds across the buccal mucosa was designed. Porcine buccal mucosa was
      mounted between two chambers with flow through capacity in both the donor and
      receptor chambers. The permeability of caffeine (CAF), triamcinolone acetonide
      (TAC), and estradiol (E(2)) was determined over 4 h and flux values were compared
      to those obtained using a modified Ussing chamber (MUC). No significant
      differences in the flux of each probe compound were observed using either the MUC
      or the novel FT cell. The design of the FT cell allowed for monitoring appearance
      of receptor solution within the donor chamber during the initial equilibration
      period, allowing for visual inspection of tissue integrity. These permeability
      studies demonstrate that this FT cell is a suitable alternative model for
      assessing drug permeability across the buccal mucosa, without the limitations
      associated with the static MUC. This novel model was then utilized to determine
      whether salmeterol xinafoate (SX) could permeate the buccal mucosa at
      concentrations expected in the oral cavity following inhalation. Concentration
      dependent studies demonstrated that SX permeates the buccal mucosa via passive
      diffusion and that oral mucosal absorption may contribute significantly to the
      overall systemic exposure of inhaled SX.

PMID- 19408307
TI  - IgE, allergy, and risk of glioma: update from the San Francisco Bay Area Adult
      Glioma Study in the temozolomide era.
AB  - The consistently observed inverse relationship of allergic conditions with glioma
      risk and our previous demonstration that immunoglobulin E (IgE) levels also were
      lower in glioma patients than controls suggest that atopic allergy may be related
      to a mechanism that inhibits or prevents glioma. We sought to extend these
      results with a new and larger series of patients (n = 535 with questionnaire
      data; 393 with IgE measures) and controls (n = 532 with questionnaire data; 470
      with IgE measures). As expected, glioma cases were less likely than controls to
      report history of allergies [among self-reported cases, Odds ratios (OR) = 0.59,
      95% confidence interval (CI): 0.41-0.85]. IgE levels also were lower in glioma
      cases versus controls (OR per unit log IgE = 0.89, 95% CI (0.82-0.98). However,
      this inverse relationship was only apparent among cases receiving temozolomide, a
      treatment which became part of the "standard of care" for glioblastoma patients
      during the study period. Among patients receiving temozolomide, IgE levels in
      cases whose blood samples were obtained within 30 days of diagnosis were slightly
      higher than controls, whereas IgE levels in cases whose blood sample was obtained
      >60 days after diagnosis were significantly lower than controls (OR = 0.80; 95%
      CI: 0.71-0.89). Thus, although our results robustly confirm the inverse
      association between allergy and glioma, the results for IgE are affected by
      temozolomide treatments which may have influenced IgE levels. These results have
      implications for the study of immunologic factors in glioma as well as for
      immunotherapy protocols for treating glioma.

PMID- 19408310
TI  - Time-dependent insulin oligomer reaction pathway prior to fibril formation:
      cooling and seeding.
AB  - The difficulty in identifying the toxic agents in all amyloid-related diseases is
      likely due to the complicated kinetics and thermodynamics of the nucleation
      process and subsequent fibril formation. The slow progression of these diseases
      suggests that the formation, incorporation, and/or action of toxic agents are
      possibly rate limiting. Candidate toxic agents include precursors (some at very
      low concentrations), also called oligomers and protofibrils, and the fibrils.
      Here, we investigate the kinetic and thermodynamic behavior of human insulin
      oligomers (imaged by cryo-EM) under fibril-forming conditions (pH 1.6 and 65
      degrees C) by probing the reaction pathway to insulin fibril formation using two
      different types of experiments-cooling and seeding-and confirm the validity of
      the nucleation model and its effect on fibril growth. The results from both the
      cooling and seeding studies confirm the existence of a time-changing oligomer
      reaction process prior to fibril formation that likely involves a rate-limiting
      nucleation process followed by structural rearrangements of intermediates (into
      beta-sheet rich entities) to form oligomers that then form fibrils. The latter
      structural rearrangement step occurs even in the absence of nuclei (i.e., with
      added heterologous seeds). Nuclei are formed at the fibrillation conditions (pH
      1.6 and 65 degrees C) but are also continuously formed during cooling at pH 1.6
      and 25 degrees C. Within the time-scale of the experiments, only after increasing
      the temperature to 65 degrees C are the trapped insulin nuclei and resultant
      structures able to induce the structural rearrangement step and overcome the
      energy barrier to form fibrils. This delay in fibrillation and accumulation of
      nuclei at low temperature (25 degrees C) result in a decrease in the mean length
      of the fibers when placed at 65 degrees C. Fits of an empirical model to the data
      provide quantitative measures of the delay in the lag-time during the nucleation
      process and subsequent reduction in fibril growth rate resulting from the
      cooling. Also, the seeding experiments, within the time-scale of the
      measurements, demonstrate that fibers can initiate fast fibrillation with
      dissolved insulin (fresh or taken during the lag-period) but not with other
      fibers. Qualitatively this is explained with a conjectual free-energy space plot.

PMID- 19408311
TI  - Identification and characterization of a novel CXC chemokine in xenograft tumor
      induced by mas-overexpressing cells.
AB  - Overexpressions of G protein-coupled receptor (GPCR) with elevated downstream
      signaling events have been reported in various tumors. However, the cellular
      mechanism that GPCR overexpression leads to tumor formation is largely unknown.
      The orphan GPCR mas was originally isolated from a human epidermoid carcinoma. In
      vivo studies of mas-overexpressing cells suggested that xenograft tumor formation
      was positively correlated with the levels of mas expression. Histochemical
      analysis indicated that xenograft tumor consisted of mas-transfected and stromal
      cells. Biochemical analyses revealed that cells overexpressing mas exhibited
      significantly increased anchorage-independent growth, whereas there was no
      significant difference in cell proliferation in comparison with empty vector
      transfected control cells. Expression profiling using mRNA differential display
      and Northern analysis indicated an elevated expression of GRO and a novel CXC
      chemokines, tumor-induced factor (TIF), in mas-transfected cells and xenograft
      tumor. Bacterially expressed recombinant TIF was found to act as a neutrophil
      chemoattractant in a chemotactic assay. These results suggest that mas
      overexpression enables anchorage-independent growth of transformed cells, and
      interplays of secreted chemokines with stromal cells modulate xenograft tumor
      formation. Importantly, a novel CXC chemokine, TIF, was identified in the
      xenograft tumor tissues.

PMID- 19408313
TI  - Rapid depletion of dissolved oxygen in 96-well microtiter plate Staphylococcus
      epidermidis biofilm assays promotes biofilm development and is influenced by
      inoculum cell concentration.
AB  - Biofilm-related research using 96-well microtiter plates involves static
      incubation of plates indiscriminate of environmental conditions, making oxygen
      availability an important variable which has not been considered to date. By
      directly measuring dissolved oxygen concentration over time we report here that
      dissolved oxygen is rapidly consumed in Staphylococcus epidermidis biofilm
      cultures grown in 96-well plates irrespective of the oxygen concentration in the
      gaseous environment in which the plates are incubated. These data indicate that
      depletion of dissolved oxygen during growth of bacterial biofilm cultures in 96
      well plates may significantly influence biofilm production. Furthermore higher
      inoculum cell concentrations are associated with more rapid consumption of
      dissolved oxygen and higher levels of S. epidermidis biofilm production. Our data
      reveal that oxygen depletion during bacterial growth in 96-well plates may
      significantly influence biofilm production and should be considered in the
      interpretation of experimental data using this biofilm model.

PMID- 19408312
TI  - Developmental expression of odorant-binding proteins and chemosensory proteins in
      the embryos of Locusta migratoria.
AB  - We have investigated the development of chemosensilla and the secretion of
      odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) in the embryo of
      Locusta migratoria manilensis. We first report the changes of each sensillum in
      embryo just preceding hatch in detail and show that different sensilla have
      different developmental processes. Trichogen cells are first involved in forming
      the structure of pegs, and then, after retraction, they start secreting OBPs and
      CSPs in the sensillar lymph. The synthesis of LmigOBP1 starts during the
      embryogenesis about 0.5 h preceding hatching, specifically in sensilla trichodea
      and basiconica of the antenna. LmigOBP2, instead, was only found in the outer
      sensillum lymph (oSl) of sensilla chaetica of the antenna, while we could not
      detect LmigOBP3 in any type of sensilla of the antenna. The ontogenesis of CSPs
      in the embryos is similar to that of OBPs. Expression of CSPI homolog in Locusta
      migratoria is detected using the antiserum raised against SgreCSPI. CSPI is
      specifically expressed in the outer sensillum lymph of sensilla chaetica of the
      antenna, and anti-LmigCSPII dose not label any sensilla of the embryos. These
      data indicate that in locusts, OBPs and CSPs follow different temporal expression
      patterns, and also that OBPs are expressed in different types of sensilla.

PMID- 19408314
TI  - Impact of lactic acid on cell proliferation and free radical-induced cell death
      in monolayer cultures of neural precursor cells.
AB  - Biomaterials prepared from polyesters of lactic acid and glycolic acid, or a
      mixture of the two, degrade in the presence of water into the naturally occurring
      metabolites, lactic acid and glycolic acid. While the lactic acid degradation
      product that is released from biomaterials is well tolerated by the body, lactic
      acid can influence the metabolic function of cells; it can serve as an energy
      substrate for cells, and has been shown to have antioxidant properties. Neural
      precursor cells, a cell population of considerable interest as a source of cells
      for neural tissue regeneration strategies, generate a high amount of reactive
      oxygen species, and when associated with a degradable biomaterial, may be
      impacted by released lactic acid. In this work, the effect of lactic acid on a
      neural cell population containing proliferative neural precursor cells was
      examined in monolayer culture. Lactic acid was found to scavenge exogenously
      added free radicals produced in the presence of either hydrogen peroxide or a
      photoinitiator (I2959) commonly utilized in the preparation of photopolymerizable
      biomaterials. In addition to its effect on exogenously added free radicals,
      lactic acid reduced intracellular redox state, increased the proliferation of the
      cell population, and modified the cell composition. The findings of this study
      provide insight into the role that lactic acid plays naturally on developing
      neural cells and are also of interest to biomaterials scientists that are focused
      on the development of degradable lactic-acid-based polymers for cell culture
      devices. The effect of lactic acid on other cell populations may differ and
      should be characterized to best understand how cells function in degradable cell
      culture devices.

PMID- 19408316
TI  - Integrated fragmentation of human IgG and purification of Fab using a reactant
      adsorptive membrane bioreactor separator system.
AB  - This article discusses an integrated separation-reaction-separation scheme for
      producing Fab fragment directly from human immunoglobulin G (hIgG) present in
      serum feed. The novel reactant adsorptive membrane bioreactor separator (or
      RAMBS) system used in the current study consisted of a stack of microporous
      adsorptive membranes held within a temperature controlled module. The membrane
      stack, in the presence of salt, selectively and reversibly adsorbed hIgG by
      hydrophobic interaction while allowing most other serum proteins to flow through.
      The bound hIgG was then fragmented by pumping a solution of papain through the
      reactor at controlled temperature and flow rate. The salt concentration and pH
      for reaction and separation were systematically optimized using pure hIgG as
      reactant. The Fab fragment was separated from undigested hIgG and other
      byproducts such as Fc fragment based on their differences in hydrophobicity.
      Under optimal conditions, Fab was obtained in the reaction flow through while the
      other proteins remained bound to the membrane, these being subsequently eluted by
      lowering the salt concentration. The RAMBS system in addition to being convenient
      from process integration and intensification points of view also showed higher
      catalytic efficiency of papain in comparison to that in liquid phase reactions.

PMID- 19408315
TI  - Generic plasmid DNA production platform incorporating low metabolic burden seed
      stock and fed-batch fermentation processes.
AB  - DNA vaccines have tremendous potential for rapid deployment in pandemic
      applications, wherein a new antigen is "plugged" into a validated vector, and
      rapidly produced in a validated, fermentation-purification process. For this
      application, it is essential that the vector and fermentation process function
      with a variety of different antigen genes. However, many antigen genes are
      unpredictably "toxic" or otherwise low yielding in standard fermentation
      processes. We report cell bank and fermentation process unit operation
      innovations that reduce plasmid-mediated metabolic burden, enabling successful
      production of previously known toxic influenza hemagglutinin antigen genes. These
      processes, combined with vector backbone modifications, doubled fermentation
      productivity compared to existing high copy vectors, such as pVAX1 and gWiz,
      resulting in high plasmid yields (up to 2,220 mg/L, 5% of total dry cell weight)
      even with previously identified toxic or poor producing inserts.

PMID- 19408317
TI  - Stress in the ER leads to inflammatory bowel disease.

PMID- 19408318
TI  - Antioxidant and antibacterial activities of eugenol and carvacrol-grafted
      chitosan nanoparticles.
AB  - Essential oils are known to possess antimicrobial and antioxidant activity while
      chitosan is a biocompatible polymer with antibacterial activity against a broad
      spectrum of bacteria. In this work, nanoparticles with both antioxidant and
      antibacterial properties were prepared by grafting eugenol and carvacrol (two
      components of essential oils) on chitosan nanoparticles. Aldehyde groups were
      first introduced in eugenol and carvacrol, and the grafting of these oils to
      chitosan nanoparticles was carried out via the Schiff base reaction. The surface
      concentration of the grafted essential oil components was determined by X-ray
      photoelectron spectroscopy (XPS). The antioxidant activities of the carvacrol
      grafted chitosan nanoparticles (CHCA NPs) and the eugenol-grafted chitosan
      nanoparticles (CHEU NPs) were assayed with diphenylpicrylhydrazyl (DPPH).
      Antibacterial assays were carried out with a representative gram-negative
      bacterium, Escherichia coli (E. coli) and a gram-positive bacterium,
      Staphylococcus aureus (S. aureus). The grafted eugenol and carvacrol conferred
      antioxidant activity to the chitosan nanoparticles, and the essential oil
      component-grafted chitosan nanoparticles achieved an antibacterial activity
      equivalent to or better than that of the unmodified chitosan nanoparticles.
      Cytotoxicity assays using 3T3 mouse fibroblast showed that the cytotoxicity of
      CHEU NPs and CHCA NPs were significant lower than those of the pure essential
      oils.

PMID- 19408319
TI  - Low bone mineral density in children and adolescents with inflammatory bowel
      disease: a population-based study from Western Sweden.
AB  - BACKGROUND: Low bone mineral density (BMD) has been recognized as a potential
      problem in children with inflammatory bowel disease (IBD). The aim of the study
      was to investigate BMD in Swedish children and adolescents with IBD and to
      evaluate possible factors affecting BMD. METHODS: To evaluate BMD, all patients
      (n = 144) underwent a dual-energy X-ray absorptiometry (DXA) of the whole body
      and the spine. BMD values were expressed as Z-scores using normative pediatric
      data from Lunar (GE Medical Systems). RESULTS: In this population-based study,
      the lowest BMD values were found in the lumbar spine. The entire IBD group showed
      significantly lower BMD Z-scores of the lumbar spine (L2-L4) in comparison to
      healthy references (-0.8 standard deviation [SD], range -5.9 to 3.7 SD, P <
      0.001). Decreased BMD with a Z-score < -1 SD occurred in 46.7% of the individuals
      with Crohn's disease (CD) and in 47.0% of those with ulcerative colitis (UC). Low
      BMD with a Z-score <= -2 SD was present in 26.7% of the patients with CD and in
      24.1% of the UC patients. In a multiple regression model with BMD lumbar spine as
      the depending variable, possible factors associated with lower BMD were male
      gender, low body mass index (BMI), and treatment with azathioprine. CONCLUSIONS:
      Low BMD is prevalent in Swedish pediatric patients with IBD. Possible risk
      factors for lower BMD are male gender, low BMI, and treatment with azathioprine,
      as a probable marker of disease course severity.

PMID- 19408320
TI  - Activation of the cannabinoid 2 receptor (CB2) protects against experimental
      colitis.
AB  - BACKGROUND: Activation of cannabinoid (CB)(1) receptors results in attenuation of
      experimental colitis. Our aim was to examine the role of CB(2) receptors in
      experimental colitis using agonists (JWH133, AM1241) and an antagonist (AM630) in
      trinitrobenzene sulfonic acid (TNBS)-induced colitis in wildtype and CB(2)
      receptor-deficient (CB(2) (-/-)) mice. METHODS: Mice were treated with TNBS to
      induce colitis and then given intraperitoneal injections of the CB(2) receptor
      agonists JWH133, AM1241, or the CB(2) receptor antagonist AM630. Additionally,
      CB(2) (-/-) mice were treated with TNBS and injected with JWH133 or AM1241.
      Animals were examined 3 days after the induction of colitis. The colons were
      removed for macroscopic and microscopic evaluation, as well as the determination
      of myeloperoxidase activity. Quantitative reverse-transcriptase polymerase chain
      reaction (RT-PCR) for CB(2) receptor was also performed in animals with TNBS and
      dextran sodium sulfate colitis. RESULTS: Intracolonic installation of TNBS caused
      severe colitis. CB(2) mRNA expression was significantly increased during the
      course of experimental colitis. Three-day treatment with JWH133 or AM1241
      significantly reduced colitis; AM630 exacerbated colitis. The effect of JWH133
      was abolished when animals were pretreated with AM630. Neither JWH133 nor AM1241
      had effects in CB(2) (-/-) mice. CONCLUSIONS: We show that activation of the
      CB(2) receptor protects against experimental colitis in mice. Increased
      expression of CB(2) receptor mRNA and aggravation of colitis by AM630 suggests a
      role for this receptor in normally limiting the development of colitis. These
      results support the idea that the CB(2) receptor may be a possible novel
      therapeutic target in inflammatory bowel disease.

PMID- 19408321
TI  - Adalimumab as therapy for fistulizing orofacial Crohn's disease.

PMID- 19408322
TI  - Cervical neoplasia risk in IBD: truth or hysteria?

PMID- 19408323
TI  - Physicians may inadequately address sexuality in women with inflammatory bowel
      disease.

PMID- 19408324
TI  - Clostridium difficile-associated diarrhea in Crohn's disease patients with
      ostomy.

PMID- 19408325
TI  - Rearrangement of beta-amino alcohols and application to the synthesis of
      biologically active compounds.
AB  - Beta-amino alcohols derived from natural amino acids have been used extensively
      as a powerful source of chirality. Transformation of the hydroxy group of these
      beta-amino alcohols into a good leaving group, by using trifluoroacetic
      anhydride, led to rearranged beta-amino alcohols in good yields and with high
      enantiomeric excesses. This rearrangement has allowed the transformation of
      substituted prolinols to substituted 3-hydroxypiperidines and linear beta-amino
      alcohols, issued from natural amino acids, to rearranged beta-amino alcohols.

PMID- 19408326
TI  - Chiral amino amides for the ruthenium(II)-catalyzed asymmetric transfer
      hydrogenation reaction of ketones in water.
AB  - The chiral amino amide 3 was derived from L-proline and used for the [RuCl2(p
      cymene)]2-catalyzed asymmetric transfer hydrogenation of prochiral ketones
      performed in water. Moderate to good chemical selectivities (up to 95% yield) and
      enantioselectivities (up to 90% ee) were obtained in the presence of 2 mol % of
      TBAB (n-Bu4NBr) as the phase transfer catalyst.

PMID- 19408327
TI  - Severity of postoperative recurrence in Crohn's disease: correlation between
      endoscopic and sonographic findings.
AB  - BACKGROUND: Crohn's disease (CD) recurrence is currently assessed by
      ileocolonoscopy. Small intestine contrast ultrasonography (SICUS) visualizes the
      small bowel lesions in CD, although its role after curative resection is
      undefined. We aimed to investigate the accuracy of SICUS in assessing CD
      recurrence after ileocolonic resection when using ileocolonoscopy as a gold
      standard. The correlation between the bowel wall thickness (BWT) measured by
      SICUS and the endoscopic score of recurrence was also assessed. METHODS: The
      analysis included 72 CD patients with ileocolonic resection requiring
      ileocolonoscopy, undergoing SICUS within 6 months. Recurrence was assessed by
      ileocolonoscopy using the Rutgeerts' score. SICUS was performed after PEG
      ingestion and findings compatible with recurrence included: increased BWT (>3
      mm), bowel dilation (>25 mm) or stricture (<10 mm). RESULTS: Ileocolonoscopy
      detected recurrence in 67/72 (93%) patients. SICUS detected findings compatible
      with recurrence in 62/72 (86%) patients (5 false negative (FN), 4 false positive
      (FP), 1 true negative (TN), 62 true positive (TP)), showing a 92.5% sensitivity,
      20% specificity, and 87.5% accuracy for detecting CD recurrence. The BWT detected
      by SICUS was correlated with the Rutgeerts' score (P = 0.0001; r = 0.67). The
      median BWT, the extent of the ileal lesions, and the prestenotic dilation were
      higher in patients with an endoscopic degree of recurrence >or=3 versus <or=2 (P
      < 0.001) and the lumen diameter was lower in patients with a Rutgeerts' score
      >or=3 versus <or=2 (P < 0.0001). CONCLUSIONS: : Although SICUS and
      ileocolonoscopy provide different views of the small bowel, SICUS shows a
      significant correlation with the endoscopic findings. SICUS may represent an
      alternative noninvasive technique for assessing CD recurrence after ileocolonic
      resection.

PMID- 19408328
TI  - Parallel kinetic resolution of D-labelled 2-aryl-propionic and butanoic acids
      using quasi-enantiomeric combinations of oxazolidin-2-ones.
AB  - The parallel kinetic resolution of racemic 2-aryl-2-deuterio-propionic and
      butanoic acids using an equimolar combination of quasi-enantiomeric oxazolidin-2
      ones is discussed. The levels of diastereoselectivity were high leading to
      enantiomerically pure D-labeled products in good yield.

PMID- 19408329
TI  - Comparison of the effects of 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D on
      bone pathology and disease activity in Crohn's disease patients.
AB  - BACKGROUND: Vitamin D is essential for osteopenia therapy in Crohn's disease
      (CD). The active form of vitamin-D (aVD) is the 1,25(OH)2D. There are no data
      available whether aVD or plain vitamin-D (pVD) has any advantage in managing
      osteoporosis in CD or has any effect on the activity of the disease itself. Our
      work is a prospective study to compare the effects of aVD and pVD on bone
      metabolism and the clinical course of CD. METHODS: In all, 37 inactive CD
      patients were involved in the study and divided into 2 age-, gender-, and t-score
      matched groups. Group A was treated with aVD while group B received pVD.
      Osteocalcin, beta-CrossLaps, osteoprotegerin, and receptor activator nuclear
      factor kappa-B ligand concentrations were estimated at the start of the study and
      at 6 weeks and 3 and 12 months. The activity of CD was also measured clinically
      and by laboratory parameters. RESULTS: At week 6 the Crohn's Disease Activity
      Index (CDAI) scores and concentration of C-reactive protein decreased (69.44 +/-
      58.6 versus 57.0 +/- 54.89 and 15.8 +/- 23.57 mmol/L versus 7.81 +/- 3.91 mmol/L,
      respectively, P < 0.05) parallel with markers of bone turnover (beta-CrossLaps:
      0.46 +/- 0.21 ng/mL versus 0.40 +/- 0.25 ng/mL, and osteocalcin: 32.29 +/- 15.3
      ng/mL versus 29.98 +/- 14.14 ng/mL, P < 0.05); however, osteoprotegerin
      concentration (marker of osteoblast activity) increased (3.96 +/- 2.1 pg/mL
      versus 4.58 +/- 2.19 pg/mL) in group A, but did not change in group B.
      Osteocalcin and beta-CrossLaps concentrations changed more significantly by the
      3rd month; however, these changes disappeared by the 12th month. CONCLUSIONS:
      According to our study, aVD has a more prominent short-term beneficial effect on
      bone metabolism and disease activity in CD compared with pVD.

PMID- 19408330
TI  - The asymmetric synthesis of (R,R)-formoterol via transfer hydrogenation with
      polyethylene glycol bound Rh catalyst in PEG2000 and water.
AB  - (R,R)-formoterol was synthesized in seven steps with 4-hydroxyl-3-nitro
      acetophenone as the starting material. The key intermediate, the chiral secondary
      alcohol 4, was prepared via Rh-catalyzed asymmetric transfer hydrogenation with
      (S,S)-PEGBsDPEN as the ligand and sodium formate as the hydrogen donor under mild
      conditions. With a mixture of PEG 2000 and water as the reaction media, the
      catalyst system could be recycled four times.

PMID- 19408331
TI  - Asymmetric catalysis of homo-coupling of 3-substituted naphthylamine and hetero
      coupling with 3-substituted naphthol leading to 3,3'-dimethyl-2,2'
      diaminobinaphthyl and -2-amino-2'-hydroxybinaphthyl.
AB  - Optically active 3,3'-dimethyl-2,2'-diamino-1,1'-binaphthyl (DM-DABN) and 3,3'
      dimethyl-2-amino-2'-hydroxybinaphthyl (DM-NOBIN) derivatives were synthesized by
      Cu-(-)-sparteine complex-catalyzed enantioselective homo- and hetero-coupling of
      2-naphthylamine, respectively. The difference in enantioselectivity was observed
      by changing the concentration of oxygen.

PMID- 19408332
TI  - ECD cotton effect approximated by the Gaussian curve and other methods.
AB  - To determine the absolute configuration of chiral compounds, theoretical
      calculations of ECD spectra have been extensively carried out, where the shape of
      component CD Cotton effects was approximated by the Gaussian distribution curve.
      However, in some articles, errors are found in the equations of Gaussian curve
      expressing CD Cotton effects. In this short review, the correct and general forms
      of the Gaussian equation and the approximation of the CD curve by other methods
      are described.

PMID- 19408333
TI  - Absolute configuration determination and conformational analysis of (-)-(3S,6S)
      3alpha,6beta-diacetoxytropane using vibrational circular dichroism and DFT
      techniques.
AB  - The absolute configuration of semisynthetic (-)-3alpha,6beta-acetoxytropane 1,
      prepared from (-)-6beta-hydroxyhyoscyamine 2, has been determined using
      vibrational circular dichroism (VCD) spectroscopy. The vibrational spectra (IR
      and VCD) were calculated using DFT at the B3LYP/DGDZVP level of theory for the
      eight more stable conformers which account for 99.97% of the total relative
      abundance in the first 10 kcal/mol range. The calculated VCD spectra of all
      considered conformations showed two distinctive spectral ranges, one between 1300
      and 1200 cm(-1), and the other one in the 1150-950 cm(-1) region. When compared
      with the experimental VCD spectrum, the first spectral region confirmed the
      calculated conformational preferences, whereas the second region showed little
      change with conformation, thus allowing the determination of the absolute
      configuration of 1 as (3S,6S)-3alpha,6beta-diacetoxytropane. Also, the bands in
      the second region showed similarities between 1 and 2 in both the experimental
      and calculated VCD spectra, suggesting that these bands are mainly related to the
      absolute configuration of the rigid tropane ring system, since they show
      conformational independency, no variations with the nature of the substituent,
      and are composed by closely related vibrational modes.

PMID- 19408334
TI  - Musculoskeletal manifestations of inflammatory bowel disease.
AB  - Extraintestinal manifestations develop in ~25% of patients with inflammatory
      bowel disease (IBD). Musculoskeletal symptoms are the most common extraintestinal
      manifestations of IBD, often associated with colonic involvement, and present as
      either articular (arthritis) or periarticular inflammation including enthesitis,
      myositis, or soft tissue rheumatism (fibromyalgia). Musculoskeletal
      manifestations can precede or be synchronous with the development of bowel
      disease or develop following the diagnosis of IBD. Their clinical course often
      correlates with IBD activity but it can also be independent of the activity of
      bowel disease. Controlling intestinal inflammation remains the cornerstone
      therapeutic approach for the musculoskeletal manifestations of IBD.

PMID- 19408335
TI  - Immunizations in patients with inflammatory bowel disease.
AB  - Patients receiving immunosuppressive therapies may be at increased risk for
      complications of vaccine preventable diseases, including influenza, varicella,
      and pneumococcus. However, studies suggest that patients with chronic illness may
      be inadequately immunized. In part, this is because of a paucity of formal
      vaccine studies in immune compromised populations. This review discusses the
      methods one uses to assess vaccine efficacy and provides an update on currently
      known data on the vaccine antibody responses in immune compromised hosts.
      Currently published studies suggest that influenza vaccine can be safely
      administered to patients with IBD on immunosuppression, and is effective in the
      majority of patients. Further formal studies with other inactivated vaccines
      (e.g., pneumococcal vaccine, meningitis vaccine) should be conducted. While some
      studies in immune compromised hosts suggest the live attenuated varicella vaccine
      can be given without adverse events, administration of this vaccine in patients
      on immunosuppression remains controversial.

PMID- 19408336
TI  - Resource use and societal costs for Crohn's disease in Sweden.
AB  - BACKGROUND: The usual onset of Crohn's disease (CD) is between 15 and 30 years of
      age, thus affecting people during their most economically productive period in
      life. METHODS: This study intended to estimate societal costs and health-related
      quality of life (HRQoL) in Swedish patients in different stages of CD. Cross
      sectional data on disease activity (measured with the Harvey-Bradshaw Index
      [HBI]), direct medical resource use, work productivity, and HRQoL (assessed using
      the 15D instrument) were collected for 420 patients by questionnaires to
      patients, to the treating physician, and from medical records. Based on HBI,
      current treatment, and response to treatment, patients were classified into the
      following disease states: Remission, Response, Active, Refractory, and Surgery.
      RESULTS: The average 4-week cost per patient in 2007 was estimated at ?721 (USD
      988), of which 64% was due to lost productivity. The total 4-week cost of care
      was ?255 (USD 349) in Remission, ?831 (USD 1138) in Response, ?891 (USD 1220) in
      Active, ?1360 (USD 1864) in Refractory, and ?16984 (USD 23269) in Surgery. HBI
      was the most important predictor of costs of care--a 1-point increase in HBI
      increased total costs by 25% (P < 0.001). HRQoL differed between the disease
      states: 0.92 in Remission, 0.90 in Response, 0.82 in Active, 0.81 in Refractory,
      and 0.77 in Surgery. CONCLUSIONS: Patients in remission have the lowest costs and
      the highest HRQoL. Patients responding to treatment have lower costs of care than
      patients with high disease activity who are not treated or do not respond to
      treatment. Thus, total costs of care might be reduced by efficient treatment.

PMID- 19408337
TI  - Adipokine signaling in inflammatory bowel disease.
AB  - While the incidence of inflammatory bowel disease (IBD) is still increasing, the
      etiology has not finally been dissected. The main hypothesis suggests that the
      mucosal immune system is hyperresponsive to dietary factors and commensal
      bacteria in genetically predisposed individuals. Burrill Crohn himself described
      a local hypertrophy of the mesenteric fat tissue adjacent to the segments of
      inflamed intestine. In addition, more recent data indicate altered local
      expression and serum levels of some adipocyte-derived mediators (adipokines) with
      immune-modulating capacities in IBD. This review focuses on the role of adipose
      tissue and adipokines in the immune system, with particular focus on the mucosal
      immune system. The available data will serve to establish a working hypothesis on
      how the mesenteric fat tissue contributes to the pathogenesis of Crohn's disease.

PMID- 19408339
TI  - Oral and intravenous iron treatment in inflammatory bowel disease: hematological
      response and quality of life improvement.
AB  - BACKGROUND: The aim was to evaluate the efficacy and tolerance of oral and
      intravenous iron treatment in anemic inflammatory bowel disease (IBD) patients,
      considering both hematological and quality-of-life outcomes. METHODS: We
      performed a prospective multicenter study in IBD patients with iron deficiency
      anemia. Patients having hemoglobin >10 g/dL were prescribed oral ferrous sulfate.
      If hemoglobin <10 g/dL, intravenous (sucrose) iron was administered. Oral iron
      intolerant patients were changed to intravenous treatment. Clinical
      (Truelove/Harvey-Bradshaw), hematological (response defined as hemoglobin
      normalization), and quality-of-life (shortened CCVEII-9 questionnaire)
      evaluations were performed at baseline and at 3 and 6 months. RESULTS: 100 IBD
      patients (59 Crohn's disease, 41 ulcerative colitis) were included. Mean basal
      hemoglobin levels were 10.8 +/- 1.3 g/dL (range, 6.6-12.9). Seventy-eight
      patients received oral treatment and 22 intravenous iron. Hemoglobin
      normalization was achieved in 86% of patients: 89% with oral, and 77% with
      intravenous iron. An IBD activity increase was not demonstrated in any patient.
      Four patients (5.1%) showed oral iron intolerance leading to discontinuation of
      treatment. No adverse events were reported for intravenous iron. Hemoglobin
      correlated with CCVEII-9 (P < 0.001). The CCVEII-9 score increased in patients
      who normalized hemoglobin levels in 3 months (from 58 +/- 9 to 73 +/- 10) or 6
      months (54 +/- 9, 68 +/- 12, and 74 +/- 10) (P < 0.001). CONCLUSIONS: Oral iron
      treatment is effective and well tolerated in most IBD patients, and does not
      exacerbate the symptoms of the underlying IBD. Intravenous iron, on the other
      hand, is an effective and safe alternative treatment for iron deficiency anemia
      in more severely anemic or intolerant patients. Anemia correction with iron
      treatment is associated with a relevant improvement in the patients' quality of
      life.

PMID- 19408338
TI  - Filaggrin loss-of-function variants are associated with atopic comorbidity in
      pediatric inflammatory bowel disease.
AB  - BACKGROUND: Pediatric inflammatory bowel disease (IBD) has a high prevalence of
      coexistent atopy. Filaggrin (FLG) loss-of-function variants (null-alleles) are
      associated with eczema and asthma in association with eczema. The aim was to
      assess the contribution of FLG null-alleles to pediatric IBD susceptibility and
      to coexistent atopy (eczema, asthma, allergic rhinitis, or food allergy).
      METHODS: FLG variants (R501X and 2282del4) were genotyped in 403 children with
      IBD, 683 parents, and 996 population controls. RESULTS: In all, 11% of IBD
      patients carried at least 1 FLG null-allele compared to 11% of population
      controls (P > 0.4). Carriage of 1 or more null-alleles in patients with atopy
      (present in 52% of IBD patients) differed from IBD patients without atopy (14%
      versus 6%, P = 0.01; odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-5.1).
      The effect of FLG null-alleles was strongest for eczema (19% versus 7%, P =
      0.0003; OR 3.3, 95% CI 1.7-6.6) and food allergy (28% versus 8%, P = 0.0001; OR
      4.5, 95% CI 2.0-10.0). The presence of more than 1 atopic disease tended to
      increase the associated OR: eczema + asthma (23% versus 7%, P = 0.001; OR 3.9,
      95% CI 1.6-9.1), eczema + asthma + allergic rhinitis (29% versus 7%, P = 0.0006;
      OR 5.4, 95% CI 1.9-15.4) and eczema + asthma + allergic rhinitis + food allergy
      (45% versus 6%, P < 10(-4); OR 12.2, 95% CI 3.2-46.3). Logistic regression
      analysis of IBD cases confirmed the association of carriage of an FLG null-allele
      with atopy (P = 0.01; OR 2.4, 95% CI 1.2-5.1) and co-occurrence of different
      forms of atopy (P = 0.003; OR 3.5, 95% CI 1.5-8.1). CONCLUSIONS: Filaggrin null
      alleles have no effect on IBD susceptibility but contribute to coexistent eczema
      and food allergy.

PMID- 19408340
TI  - Open-label study of adalimumab in patients with ulcerative colitis including
      those with prior loss of response or intolerance to infliximab.
AB  - BACKGROUND: The aim of this study was to assess the clinical benefit and
      tolerability of adalimumab, a fully human monoclonal antibody to tumor necrosis
      factor (TNF), in patients with ulcerative colitis (UC). METHODS: Patients with
      active UC, including those who had lost response or developed intolerance to the
      chimeric anti-TNF antibody infliximab, were enrolled in a 24-week uncontrolled
      trial. Patients were treated with subcutaneous adalimumab 160 mg at week 0, 80 mg
      at week 2, and 40 mg every other week starting at week 4. After week 8 the dose
      could be escalated to 40 mg weekly for incomplete response. Outcome measures
      included clinical response and remission and mucosal healing. RESULTS: Twenty
      patients were enrolled, of whom 13 had previously received infliximab. Seven
      patients had dose escalation of adalimumab between weeks 8 and 16, from 40 mg
      every other week to 40 mg weekly, due to incomplete response. The rates of
      clinical response were 25% at week 8 and 50% at week 24. The rates of clinical
      remission were 5% at week 8 and 20% at week 24. The rate of mucosal healing was
      30% at week 8. The rates of clinical response and remission and mucosal healing
      were similar in infliximab-naive and previously exposed patients. None of the
      patients experienced hypersensitivity reactions during treatment with adalimumab.
      CONCLUSIONS: Adalimumab is well tolerated and appears to be a clinically
      beneficial option for patients with UC, including those who have previously lost
      their response to or cannot tolerate infliximab.

PMID- 19408341
TI  - Varicella pneumonia in an immunocompromised inflammatory bowel disease patient.

PMID- 19408342
TI  - Heterogeneity of commercial recombinant human growth hormone (r-hGH) preparations
      containing a thioether variant.
AB  - The objective of the present study was to assess (I) the potential presence of a
      recently discovered thioether variant in commercially available recombinant human
      growth hormone (r-hGH) preparations, and (II) the impact of the thioether
      modification on the in-vivo bioactivity and the receptor binding kinetics.
      Samples were tested employing European (EP) and US Pharmacopeia (USP) Somatropin
      monograph and mass spectrometry methods. None of the international standards
      contained this variant. All products conformed to EP specifications but six out
      of eight lots contained the variant. An artificially enriched thioether sample
      exhibited a significantly reduced in vivo biopotency and altered receptor-binding
      properties compared with a control. The absence of the variant in the pituitary
      hGH standard, and the possibility to generate it artificially suggests that it is
      not naturally occurring and that it may arise from an uncontrolled manufacturing
      process. Controlled studies may be required to assess its clinical efficacy and
      safety. EP and USP methods may need to be adapted to reliably detect the presence
      of the variant.

PMID- 19408343
TI  - Lung cancer susceptibility and prognosis associated with polymorphisms in the
      nonhomologous end-joining pathway genes: a multiple genotype-phenotype study.
AB  - BACKGROUND: Nonsmall cell lung cancer (NSCLC) frequently exhibits genomic
      instability, such as high fractional allelic loss (FAL). Genomic instability may
      result from unrepaired or misrepaired double-strand breaks (DSBs). The authors of
      this report postulated that polymorphisms in genes of the nonhomologous end
      joining (NHEJ) pathway, which is the major DSB repair pathway in mammalian cells,
      may modulate lung cancer susceptibility and prognosis. METHODS: Patients with
      NSCLC (n = 152) and a group of appropriate age-matched and sex-matched controls
      (n = 162) were subjected to genotype analysis of the NHEJ pathway genes x-ray
      repair complementing defective repair in Chinese hamster cells 6 (Ku70)
      (reference single nucleotide polymorphism number [rs] 2267437), x-ray repair
      complementing defective repair in Chinese hamster cells 5 (Ku80) (rs3835), x-ray
      repair complementing defective repair in Chinese hamster cells 4 (XRCC4)
      (rs1805377), and DNA ligase IV (LIG4) (rs1805388). The gene-gene interaction
      (joint effect), genotype-environmental (ie, smoking) correlation, and genotype
      phenotype (ie, FAL) correlation were examined. The Kaplan-Meier method and log
      rank tests were used to assess the prognostic effect. RESULTS: There was a
      significant association between the XRCC4 and LIG4 genotypes with NSCLC risk in
      an analysis of individual polymorphism associations, and the risk of NSCLC
      increased further in a combined analysis of multiple polymorphisms (adjusted odds
      ratio [OR], 8.74). The patients who had a homozygous variant guanine/guanine
      genotype of the XRCC4 gene had a poorer prognosis compared with other patients (P
      = .015). There was a significant difference between the patient smokers and
      controls for XRCC4 (adjusted OR, 2.67) and LIG4 (adjusted OR, 2.04). In addition,
      polymorphisms in XRCC4 and LIG4 were linked significantly with patients who had
      high FAL (adjusted OR, 2.03-3.84). CONCLUSIONS: To the authors' knowledge, this
      is the first nested case-control study to demonstrate a significant association
      between the polymorphisms of genes in the NHEJ pathway and lung cancer
      susceptibility and prognosis. The results may be useful for risk assessment and
      disease monitoring of patients with NSCLC.

PMID- 19408344
TI  - Rapid identification of gallotannins from Chinese galls by matrix-assisted laser
      desorption/ionization time-of-flight quadrupole ion trap mass spectrometry.
AB  - Chinese gall, a conventional traditional Chinese medicine, contains high levels
      of gallotannins. A rapid method for direct analysis of the gallotannins without
      using any troublesome sample pretreatments was developed using matrix-assisted
      laser desorption/ionization time-of-flight quadrupole ion trap mass spectrometry
      (MALDI-QIT-TOF MS) to successfully identify the gallotannin components in the
      crude extract of Chinese galls within several minutes. The high quality of the MS
      and MS(2) spectra acquired clearly showed that hydrolysable tannins in Chinese
      galls were identified as a series of the gallotannins with degrees of
      polymerization (DP) of 4-11 galloyl units. The MS(2) data indicated that the
      identified gallotannins with DP of 4-7 galloyl units had clear fragmentation with
      loss of 1-5 galloyl units which were further deprived of 1-3 water moieties. This
      technique may be used for rapid evaluation and screening of hydrolysable tannins
      in medicinal plants.

PMID- 19408345
TI  - Differentiation of configurations of the phenylbutenoid dimer derivatives from
      Zingiber cassumunar by tandem mass spectrometry.
AB  - High-performance liquid chromatography/electrospray tandem mass spectrometry was
      developed to distinguish isomers and compounds of similar structures with
      different configurations in the rhizomes of Z. cassumunar. Energy-resolved
      breakdown curves were utilized to differentiate four compounds. Compounds 2
      (3R,4S) and 4 (3R,4R) were a pair of stereoisomers which could be distinguished
      easily by breakdown curves. The breakdown curve of compound 1 was identical to
      that of compound 2, which suggested that the configuration of compound 1 was
      (3R,4S) or (3S,4R). The breakdown curve of compound 3 was completely different
      from those of compounds 1, 2 and 4, and it might be that the configuration of the
      double bond of compound 3 was different from the other three compounds. Hence,
      the described method using breakdown curves has great potential in the
      distinguishing of isomers and compounds of similar structure with different
      configurations.

PMID- 19408347
TI  - The role of ADAMs in disease pathophysiology.
AB  - The ADAMs are a family of multidomain transmembrane and secreted proteins
      involved in both proteolysis and cell adhesion. Altered expression of specific
      ADAMs is implicated in the pathophysiology of several diseases including
      rheumatoid arthritis, Alzheimer's disease, cardiac hypertrophy, asthma and
      cancer. Of these different diseases, it is in cancer where most research has been
      carried out. Multiple ADAMs, including ADAM-9, ADAM-10, ADAM-12, ADAM-15 and ADAM
      17, have been shown to play a role in either cancer formation or progression.
      Consistent with these findings, increased expression of specific ADAMs in several
      cancer types was found to correlate with features of aggressive disease and poor
      prognosis. Currently, selective ADAM inhibitors against ADAM-10 and ADAM-17 are
      undergoing clinical trials for the treatment of cancer. Further work is required
      in order to establish a causative role for ADAMs in rheumatoid arthritis,
      Alzheimer's disease, cardiac hypertrophy and asthma.

PMID- 19408346
TI  - Sociocultural determinants of men's reactions to prostate cancer diagnosis.
AB  - OBJECTIVE: To develop a better understanding of how men react to being diagnosed
      with prostate cancer and identify factors that influence these responses, we
      conducted an observational study to identify sociocultural predictors of men's
      psychological reactions. METHODS: Participants were 70 African American and 124
      white prostate cancer patients who completed a structured telephone interview
      that evaluated psychological reactions in terms of intrusive thoughts about
      cancer and attempts to avoid cancer-related thoughts and feelings. Perceptions of
      disease-specific stress, cultural beliefs and values, and social constraints were
      also assessed during the interview. RESULTS: There were no racial differences in
      men's reactions to being diagnosed with prostate cancer; however, greater
      perceptions of disease-specific stress, increasing levels of present temporal
      orientation, and more social constraints had significant positive effects on
      avoidant reactions. Greater perceptions of stress also had a significant positive
      effect on intrusive thoughts. CONCLUSIONS: The results of this study highlight
      the need for individualized approaches to help men address their thoughts and
      feelings about being diagnosed with prostate cancer. These efforts should include
      strategies that help men to communicate more effectively with social support
      resources and address cultural beliefs and values related to temporal
      orientation.

PMID- 19408349
TI  - Apolipoprotein B gene polymorphisms g.2488C>T and g.4154G>A are not associated
      with coronary artery disease in a Brazilian population.

PMID- 19408348
TI  - A modified ELISA for improved detection of IgA, IgG, and IgM anti-tissue
      transglutaminase antibodies in celiac disease.
AB  - BACKGROUND: Serum IgA antibodies against tissue transglutaminase (tTG) are
      reliable markers for celiac disease (CD), still the diagnostic performance of
      anti-tTG immunoassays can be improved. A novel ELISA, using fibronectin (FN) as
      tTG binding protein, was evaluated for the detection of anti-tTG antibodies in
      CD. METHODS: Sera from 173 children with untreated CD and 97 controls were
      analyzed for IgA, IgG, and IgM anti-tTG antibodies with ELISA using human
      recombinant tTG with or without FN. RESULTS: The areas under the ROC (receiver
      operating characteristic) curves were significantly higher for FN/tTG ELISA
      compared to tTG ELISA for IgG (0.930 versus 0.809; p < 0.001) and IgM (0.850
      versus 0.811; p = 0.019), but not for IgA (0.977 versus 0.970; p = 0.356),
      respectively. At the fixed diagnostic specificity (100% for IgA and IgM, 99% for
      IgG), the sensitivity of all three FN/tTG ELISA (92.5% for IgA, 60.7% for IgG,
      50.3% for IgM) exceeded those obtained in tTG ELISA (89.0% for IgA, 48.6% for
      IgG, 38.7% for IgM; p < 0.05). The combined use of IgA- and IgG-FN/tTG ELISA
      resulted in 95.4% sensitivity and 99.0% specificity for CD. CONCLUSIONS: Using FN
      to bind tTG improves the diagnostic performance of solid phase anti-tTG antibody
      assays for childhood CD.

PMID- 19408350
TI  - Non-diffeomorphic registration of brain tumor images by simulating tissue loss
      and tumor growth.
AB  - Although a variety of diffeomorphic deformable registration methods exist in the
      literature, application of these methods in the presence of space-occupying
      lesions is not straightforward. The motivation of this work is spatial
      normalization of MR images from patients with brain tumors in a common
      stereotaxic space, aiming to pool data from different patients into a common
      space in order to perform group analyses. Additionally, transfer of structural
      and functional information from neuroanatomical brain atlases into the individual
      patient's space can be achieved via the inverse mapping, for the purpose of
      segmenting brains and facilitating surgical or radiotherapy treatment planning. A
      method that estimates the brain tissue loss and replacement by tumor is applied
      for achieving equivalent image content between an atlas and a patient's scan,
      based on a biomechanical model of tumor growth. Automated estimation of the
      parameters modeling brain tissue loss and displacement is performed via
      optimization of an objective function reflecting feature-based similarity and
      elastic stretching energy, which is optimized in parallel via APPSPACK
      (Asynchronous Parallel Pattern Search). The results of the method, applied to 21
      brain tumor patients, indicate that the registration accuracy is relatively high
      in areas around the tumor, as well as in the healthy portion of the brain. Also,
      the calculated deformation in the vicinity of the tumor is shown to correlate
      highly with expert-defined visual scores indicating the tumor mass effect,
      thereby potentially leading to an objective approach to quantification of mass
      effect, which is commonly used in diagnosis.

PMID- 19408352
TI  - Swine influenza: frequently asked questions.

PMID- 19408351
TI  - The spatio-temporal mapping of epileptic networks: combination of EEG-fMRI and
      EEG source imaging.
AB  - Simultaneous EEG-fMRI acquisitions in patients with epilepsy often reveal
      distributed patterns of Blood Oxygen Level Dependant (BOLD) change correlated
      with epileptiform discharges. We investigated if electrical source imaging (ESI)
      performed on the interictal epileptiform discharges (IED) acquired during fMRI
      acquisition could be used to study the dynamics of the networks identified by the
      BOLD effect, thereby avoiding the limitations of combining results from separate
      recordings. Nine selected patients (13 IED types identified) with focal epilepsy
      underwent EEG-fMRI. Statistical analysis was performed using SPM5 to create BOLD
      maps. ESI was performed on the IED recorded during fMRI acquisition using a
      realistic head model (SMAC) and a distributed linear inverse solution (LAURA).
      ESI could not be performed in one case. In 10/12 remaining studies, ESI at IED
      onset (ESIo) was anatomically close to one BOLD cluster. Interestingly, ESIo was
      closest to the positive BOLD cluster with maximal statistical significance in
      only 4/12 cases and closest to negative BOLD responses in 4/12 cases. Very small
      BOLD clusters could also have clinical relevance in some cases. ESI at later time
      frame (ESIp) showed propagation to remote sources co-localised with other BOLD
      clusters in half of cases. In concordant cases, the distance between maxima of
      ESI and the closest EEG-fMRI cluster was less than 33 mm, in agreement with
      previous studies. We conclude that simultaneous ESI and EEG-fMRI analysis may be
      able to distinguish areas of BOLD response related to initiation of IED from
      propagation areas. This combination provides new opportunities for investigating
      epileptic networks.

PMID- 19408353
TI  - Nonnucleoside reverse transcriptase inhibitor pharmacokinetics in a large
      unselected cohort of HIV-infected women.
AB  - BACKGROUND: Small intensive pharmacokinetic (PK) studies of medications in early
      phase trials cannot identify the range of factors that influence drug exposure in
      heterogenous populations. We performed PK studies in large numbers of HIV
      infected women on nonnucleoside reverse transcriptase inhibitors (NNRTIs) under
      conditions of actual use to assess patient characteristics that influence
      exposure and evaluated the relationship between exposure and response. METHODS:
      Two hundred twenty-five women on NNRTI-based antiretroviral regimens from the
      Women's Interagency HIV Study were enrolled into 12-hour or 24-hour PK studies.
      Extensive demographic, laboratory, and medication covariate data were collected
      before and during the visit to be used in multivariate models. Total NNRTI drug
      exposure was estimated by area under the concentration-time curves. RESULTS:
      Hepatic inflammation and renal insufficiency were independently associated with
      increased nevirapine exposure in multivariate analysis: crack cocaine, high fat
      diets, and amenorrhea were associated with decreased levels (n = 106). Higher
      efavirenz exposure was seen with increased transaminase, albumin levels, and
      orange juice consumption; tenofovir use, increased weight, being African
      American, and amenorrhea were associated with decreased exposure (n = 119). With
      every 10-fold increase in nevirapine or efavirenz exposure, participants were 3.3
      and 3.6 times likely to exhibit virologic suppression, respectively. Patients
      with higher drug exposure were also more likely to report side effects on
      therapy. CONCLUSIONS: Our study identifies and quantitates previously
      unrecognized factors modifying NNRTI exposure in the "real-world" setting.
      Comprehensive PK studies in representative populations are feasible and may
      ultimately lead to dose optimization strategies in patients at risk for failure
      or adverse events.

PMID- 19408355
TI  - Risk factors for childhood leukemia. Proceedings of an International Commission
      on Non-Ionizing Radiation Protection (ICNIRP) Workshop. May 5-7, 2008. Berlin,
      Germany.

PMID- 19408356
TI  - Fundamentals, state of the art and new horizons. Proceedings of the 5th
      International Conference on Predictive Modelling in Foods. September 16-19, 2007.
      Athens, Greece.

PMID- 19408357
TI  - Iridescence: more than meets the eye. Proceedings of a workshop. February 2008.
      Tempe, Arizona.

PMID- 19408358
TI  - The Worldwide Challenge to Physiome and Systems Biology. Proceedings of the 2nd
      MEI International Symposium. December 7-9, 2007. Osaka, Japan.

PMID- 19408359
TI  - Operational effectiveness of guidelines on complete breast-feeding cessation to
      reduce mother-to-child transmission of HIV: results from a prospective
      observational cohort study at routine prevention of mother-to-child transmission
      sites, South Africa.
AB  - OBJECTIVE: Until 2006, HIV-positive women who chose to exclusively breast-feed
      were advised to completely stop breast-feeding by 6 months. We investigated
      operational feasibility and predictors of complete breast-feeding cessation
      (CBC). DESIGN: A prospective observational cohort study at 3 routine prevention
      of mother-to-child transmission sites, South Africa. METHODS: Data on "complete
      breast-feeding cessation at 24 weeks" and "not breast-feeding (NBF) for 4 days
      before the last follow-up visit at or before 24 weeks" were gathered during home
      visits (3, 5, 7, 9, 12, 16, 20, and 24 weeks). The main subgroup of interest for
      this analysis was women practicing exclusive breast-feeding/predominant breast
      feeding at 3 weeks. Univariate analysis, logistic regression, Kaplan-Meier
      Survival analysis, and Cox regression were performed. RESULTS: Eighty-eight women
      (43.6%) reported CBC. "Health staff suggesting formula use: [OR(a) 4.39 (1.76
      10.97)] and "infant hospitalization" [OR(a) 3.27 (1.37-7.79)] were the only
      significant predictors of CBC. The probability of NBF at 5, 7, 9, 12, 16, 20, and
      24 weeks was 2.8% [95% confidence interval (CI) 1.8% to 3.8%], 4.3% (3.0% to
      5.6%), 5.9% (4.4% to 7.4%, 9.8% (7.9% to 11.7%), 16.1 (13.8% to 18.4%), 23.1%
      (20.5% to 25.7%), and 37.6% (34.6% to 40.6%), respectively. Infant HIV status
      [hazard ratio 5.5 95% CI 2.4 to 12.5] was the only predictor of infant death. NBF
      was not protective against 9-month infant HIV or death in univariate and
      multivariable analysis. CONCLUSIONS: At programmatic level, CBC by 24 weeks is
      uncommon, and success seems unrelated to predetermined social, economic, and
      environmental (acceptable, feasible, affordable, sustainable, and safe AFASS)
      criteria. Thus at this level, activities that encourage CBC (amongst women
      meeting AFASS criteria) need to be identified and tested.

PMID- 19408360
TI  - Peginterferon alfa-2a and ribavirin in Latino and non-Latino whites with
      hepatitis C.

PMID- 19408354
TI  - Long-term patterns in CD4 response are determined by an interaction between
      baseline CD4 cell count, viral load, and time: The Asia Pacific HIV Observational
      Database (APHOD).
AB  - BACKGROUND: Random effects models were used to explore how the shape of CD4 cell
      count responses after commencing combination antiretroviral therapy (cART)
      develop over time and, in particular, the role of baseline and follow-up
      covariates. METHODS: Patients in Asia Pacific HIV Observational Database who
      first commenced cART after January 1, 1997, and who had a baseline CD4 cell count
      and viral load measure and at least 1 follow-up measure between 6 and 24 months,
      were included. CD4 cell counts were determined at every 6-month period after the
      commencement of cART for up to 6 years. RESULTS: A total of 1638 patients
      fulfilled the inclusion criteria with a median follow-up time of 58 months. Lower
      post-cART mean CD4 cell counts were found to be associated with increasing age (P
      < 0.001), pre-cART hepatitis C coinfection (P = 0.038), prior AIDS (P = 0.019),
      baseline viral load < or equal to 100,000 copies per milliliter (P < 0.001), and
      the Asia Pacific region compared with Australia (P = 0.005). A highly significant
      3-way interaction between the effects of time, baseline CD4 cell count, and post
      cART viral burden (P < 0.0001) was demonstrated. Higher long-term mean CD4 cell
      counts were associated with lower baseline CD4 cell count and consistently
      undetectable viral loads. Among patients with consistently detectable viral load,
      CD4 cell counts seemed to converge for all baseline CD4 levels. CONCLUSIONS: Our
      analysis suggest that the long-term shape of post-cART CD4 cell count changes
      depends only on a 3-way interaction between baseline CD4 cell count, viral load
      response, and time.

PMID- 19408361
TI  - Insect Endocrinology. Introduction.

PMID- 19408362
TI  - Biological activity of diuretic factors on the anterior midgut of the blood
      feeding bug, Rhodnius prolixus.
AB  - Probing of a host and ingestion of a blood-meal in a fifth instar Rhodnius
      prolixus results in a cascade of tightly integrated events, including salivary
      gland secretion, plasticization of the abdominal cuticle, increased ion and water
      movement across the anterior midgut (crop) and Malpighian tubules (which rapidly
      produce urine) and the regular expulsion of urine from the hindgut. In this study
      we have focussed on the role of the anterior midgut during the rapid postprandial
      diuresis. The huge blood-meal is pumped into the anterior midgut, during feeding,
      then modified by diuresis and stored until it is digested. Changes in the
      anterior midgut activity are rapid. Within minutes of the commencement of feeding
      there is an increase in the frequency of anterior midgut contractions and
      diuresis begins with the movement of salt and water across the epithelium of the
      anterior midgut into the haemolymph. While serotonin, a diuretic hormone in R.
      prolixus, is known to play a role in the physiological activity of the anterior
      midgut, we were interested in exploring further the role of serotonin, and other
      diuretic peptides. We have tested the activity of several peptides, including R.
      prolixus calcitonin-like diuretic hormone (Rhopr-DH 31), corticotropin-releasing
      factor (CRF)-like peptide from Zootermopsis nevadensis DH (Zoone-DH) and a kinin
      from Leucophaea maderae, Leucokinin 1 (LK1). These peptides families are known to
      be present in the central nervous system of R. prolixus, are putative
      neurohormones released into the haemolymph after the start of feeding, and have
      been shown to have activity on a variety of tissues involved in post-feeding
      diuresis. We show here that both serotonin and Zoone-DH increase the cAMP content
      of the anterior midgut and that serotonin, Zoone-DH and cAMP analogues increase
      absorption of water from the anterior midgut, increase the short circuit current
      and voltage, while decreasing the resistance across the epithelium. While LK1 and
      Rhopr-DH 31 do not significantly increase absorption, or short circuit current,
      LK1 does significantly decrease the resistance and transepithelial voltage of the
      anterior midgut epithelium. All of the factors studied increase the frequency of
      contractions of the anterior midgut.

PMID- 19408363
TI  - Cell types obtained from the epidural space of patients with low back
      pain/radiculopathy.
AB  - BACKGROUND: We investigated if correlations exist between medical history, tissue
      abnormalities, and cell types retrieved from the epidural space of patients with
      chronic low back pain (LBP) and chronic radicular pain (RP). METHODS: Approval
      was obtained from the Institutional Review Board for the Protection of Human
      Subjects to study 191 patients undergoing epiduroscopy. Visual inspection was
      performed and abnormal areas were identified. A specimen obtained from the area
      using a cytology brush was processed by the Thin Prep technique. Patients were
      divided into four groups based on the presence or absence and intensity of LBP
      and RP. The gender and age of the patients were recorded, as was any history of
      prior back surgery. Areas of tissue abnormalities were rated according to changes
      in vascularity and amount of fat, fibrosis, and inflammation. Stenosis was
      assessed from magnetic resonance imaging or computerized tomography scan images.
      Cytologic assessments included notations of the presence or absence of
      erythrocytes, leukocytes, cell groups, lipocytes, spindled cells, and large round
      cells. RESULTS: There was a significant difference in the number of patients from
      whom big round cells were obtained who had a high degree of LBP compared with the
      number of patients who had a high degree of both LBP and RP. CONCLUSIONS: The
      findings provide a foundation for future studies of cells obtained from similar
      patients with the goal of furthering the understanding of the pathogenesis of
      LBP/RP.

PMID- 19408365
TI  - Sexual health and GP professional development.

PMID- 19408364
TI  - Ductal endoscopy of the breast: more painful at the luteal phase?
AB  - PURPOSE: To assess the putative predictors that may influence the pain
      experienced during ductal endoscopy of the breast. METHODS: The pain experienced
      was evaluated in 19 consecutive premenopausal women with bloody nipple discharge
      scheduled for ductal endoscopy. The visual analog scale (VAS) was used to
      estimate the degree of pain. The duration of the procedure, the history of
      lactation, and the phase of the menstrual cycle were evaluated with respect to
      pain experienced. Statistical analysis followed. RESULTS: The average reported
      pain (VAS score, mean +/- standard deviation) was 5.79 +/- 1.51 while the maximum
      pain was 8.26 +/- 0.99. The average reported pain was marginally associated with
      the duration of the procedure in contrast to the maximum. Women who were at the
      luteal phase of their menstrual cycle exhibited a higher average reported pain.
      The history of breastfeeding was not associated with the average reported pain,
      but it was associated with less intense maximum pain. CONCLUSIONS: Pain during
      ductal endoscopy of the breast is influenced by a host of factors: some immutable
      (such as history of lactation) and others variable (day of menstrual cycle). The
      latter (ie, avoidance of the luteal phase) may be targeted for the minimization
      of pain.

PMID- 19408366
TI  - Liver transplant for hepatocellular cancer beyond Milan criteria.

PMID- 19408367
TI  - ["The nursing care plan, the way to express the clinical nursing opinion".
      Interview by Yasmina Ouharzoune and Sylvie Warnet].

PMID- 19408369
TI  - Dealing with dementia.

PMID- 19408368
TI  - [Competence standards in emergency nursing].

PMID- 19408370
TI  - In the spotlight. The cost of the recession to mental health.

PMID- 19408372
TI  - Lest we forget.

PMID- 19408373
TI  - Just like old times.

PMID- 19408371
TI  - Land of hope.

PMID- 19408374
TI  - Antidepressants--the solution or the problem?

PMID- 19408375
TI  - Outside the box. Personalisation has been a long time coming, but will it be
      different this time?

PMID- 19408376
TI  - Welfare writes. Are welfare rights workers becoming a dying breed?

PMID- 19408377
TI  - The bigger picture. Patient safety is key to good mental health care, but so is
      taking risks.

PMID- 19408378
TI  - New agency for a new era.

PMID- 19408380
TI  - Safety matters.

PMID- 19408379
TI  - Seventeen steps: the dementia strategy.

PMID- 19408381
TI  - Not quite right in the head.

PMID- 19408382
TI  - Doctor's orders.

PMID- 19408383
TI  - Viewpoint. How do you capture the patient's experience of mental health services?

PMID- 19408384
TI  - Transverse colon tuberculosis presenting as colonic obstruction.

PMID- 19408385
TI  - [ "Kinderkrankenschwester" 28 (2009), no. 2, p. 92].

PMID- 19408386
TI  - Pandemic peril.
AB  - As avian flu has slipped from the headlines, funding for preparedness efforts has
      lagged. But public health experts say the threat remains, and the needed actions
      are expensive. Last year, $398 million was disbursed to 62 states and territories
      to address all hazards, and that's "not a lot of money," says Gregg Pane, left,
      director of national healthcare preparedness programs. And that leaves little for
      flu programs.

PMID- 19408388
TI  - Doc groups griping over ICD-10. Critics say most physicians aren't ready for
      changes.

PMID- 19408387
TI  - Sebelius on hold. GOP, Dems disagree on fast-tracking efforts.

PMID- 19408389
TI  - Busted for snooping. Octuplet mom incident latest EHR breach in Calif.

PMID- 19408391
TI  - Beyond the turning point. CCHIT will keep pace with standards compliance needs as
      stimulus kicks in.

PMID- 19408390
TI  - Some pieces already in place. IT standards groups are well-positioned to assist
      goals of stimulus act.

PMID- 19408392
TI  - Let the spending begin ... Annual IT survey shows support for stimulus, trend
      toward spending uptick.

PMID- 19408394
TI  - [The results of extended and combined operations for locally-spread colon
      cancer].
AB  - The results of combined treatment of 385 cancer recti patients, of whom 202 --
      using the staged tactics and chemotherapy, using modified methods of pelvic
      evisceration and reconstructive-restoration operations with extended lymph node
      dissection, were analyzed. The main syndromes, characteristic for locally-spread
      cancer recti are delineated, the surgical treatment concept for this pathology
      was formulated. The combined approach application had promoted the radical and
      cytoreductive operations performance rate enhancement, the reduction of
      palliative operations performance rate, as well as severe complications
      (hemorrhage and anastomotic sutures insufficiency) occurrence rate, total
      complications rate -- by 3.8% and lethality -- by 1.9%.

PMID- 19408395
TI  - [Clinical efficacy and impact of preparation ronem on endogenous intoxication
      severity in the patients with deep burns].
AB  - Clinical efficacy of Ronem preparation was studied in injured persons, suffering
      deep burns. High efficacy of the preparation in an acute period of the burn
      disease was established concerning the reduction in severity of the syndrome of
      systemic inflammatory answer clinical signs, the infection complications
      prophylaxis, microbal sensibilization lowering and preservation of natural
      detoxication systems on subcompensation level.

PMID- 19408396
TI  - Healthy choices.
AB  - With all the pieces in place to launch comparative-effectiveness research,
      questions remain over whether it will change the U.S. healthcare system. Some
      wonder if the $1.1 billion will be spent effectively, considering patients'
      differing needs. "We want healthcare decisions to be made on how the bodies are
      different and not as if bodies were made through a machine automatically," says
      Tony Coelho.

PMID- 19408398
TI  - Still low tech. EHR adoption rates remain low: study.

PMID- 19408397
TI  - $600 billion question. Reform efforts could stall over doc payment fix.

PMID- 19408399
TI  - MACPAC spat. Critics worry about state, federal conflicts.

PMID- 19408400
TI  - Labor takes a hit. Specter's reversal has unions debating options.

PMID- 19408401
TI  - Labor comes on strong. Hospitals expect no let up in latest surge of union
      activity.

PMID- 19408402
TI  - New life for ASCs. NJ amendments give self-referral rights.

PMID- 19408403
TI  - Tricky, but worthwhile. Free-standing EDs spread access, providers' brand.

PMID- 19408404
TI  - A repeat performance. This year's roster of the 100 top hospitals includes 79
      standout facilities that have made the list more than once.

PMID- 19408405
TI  - Vibrational analysis of alpha-D-glucose trapped in Ar matrix.
AB  - The FT-IR spectra of alpha-D-glucose have been investigated by means of matrix
      isolation FT-IR spectroscopy in the 3700-200 cm-1 range and by B3LYP/6-311++G**
      density functional calculations. The joint analysis of the experimental and
      computed IR spectra supported the expected predominance of the most stable gg and
      gt conformers in the vapor phase and the minor contribution of the less stable tg
      conformer. Weak absorption bands at the edge of the OH stretching region are in
      agreement with small amounts of analogous conformers with clockwise arrangement
      of the hydrogen bonds (c-gg, c-gt, c-tg). The assignment of the IR spectra was
      carried out on the basis of the computed harmonic force field using the scaled
      quantum mechanical method of Pulay. Scale factors developed previously for the
      B3LYP/6-311++G** level proved to be well transferable except that for the OH
      torsion. The latter scale factor was adjusted on the basis of the present
      experimental data. On the basis of the calculated results, 99 bands have been
      assigned to the gg, gt, and tg conformers of alpha-D-glucose with average
      deviations of 5.0, 5.9, and 6.1 cm-1, respectively.

PMID- 19408406
TI  - Proceedings of the 32nd International Symposium on High-Performance Liquid-Phase
      Separations and Related Techniques (HPLC-2008). Baltimore, Maryland, USA. May 10
      16, 2008.

PMID- 19408407
TI  - Helping Alzheimer's patients sleep.

PMID- 19408408
TI  - Comparing procedures for stroke prevention.

PMID- 19408409
TI  - Cancer care expands to include genetic testing.

PMID- 19408410
TI  - Vanishing varicose veins.

PMID- 19408411
TI  - Common ulcer drug increases risk of osteoporosis.

PMID- 19408412
TI  - Chromatographic isolation and characterization of a novel peroxidase from large
      lima legumes.
AB  - A novel peroxidase with antifungal activity was isolated from the large lima bean
      (Phaseolus limensis) seeds. The procedure entailed extraction, ammonium sulfate
      precipitation, affinity chromatography on Affi-gel blue gel, ion exchange
      chromatography on SP-Toyopearl, and gel filtration on Sephadex G-75. The enzyme
      was adsorbed on Affi-gel blue gel and SP-Toyopearl, and possessed a molecular
      weight of 34 kDa in SDS-polyacrylamide gel electrophoresis under both reducing
      and nonreducing conditions. There was an almost 110-fold increase in specific
      activity of the purified peroxidase compared with that of the crude extract. The
      enzyme exhibited a pI of 8.6 by isoelectric focusing electrophoresis, indicating
      that it is a basic protein. The optimum pH and the optimum temperature were 5.5
      and 30 degreeC, respectively. The enzyme was stable up to 55 degreeC. It potently
      suppressed mycelial growth in Fusarium solani, Mycosphaerella arachidicola, and
      Pythium aphanidermatum with an IC50 of 76, 103, and 119 microM, respectively.

PMID- 19408413
TI  - Caring and compassion.

PMID- 19408414
TI  - Open channels: Do new cystic-fibrosis therapies hold the key to treating other
      genetic disorders?

PMID- 19408415
TI  - [Melanoma and non-melanoma skin cancer].

PMID- 19408416
TI  - [Dermoscopy: revolutionary method of diagnosis for melanoma].

PMID- 19408417
TI  - [Imiquimod: its characterization and treatment of actinic keratosis].

PMID- 19408418
TI  - [Diagnosis and treatment of non-melanoma skin neoplasm].

PMID- 19408419
TI  - [Classification and diagnosis of sebaceous gland and sweat gland neoplasms].

PMID- 19408421
TI  - [A social and demographic analysis of migrations: the small town of Limburg in
      the mid-19th century].

PMID- 19408420
TI  - [Sexual violence, scandal, and public order from the point of view of the
      legislator, the justice system, and other social actors in the 19th century].

PMID- 19408422
TI  - [The port of Antwerp and the Alsatian potash trade, 1920-50: political influences
      in a period of economic boom and in a period of crisis].

PMID- 19408424
TI  - You're the flight surgeon: Intracranial neoplasm.

PMID- 19408423
TI  - [Past and future of the Revista de Investigacion Clinica].

PMID- 19408425
TI  - This month in aerospace medicine history.

PMID- 19408426
TI  - President Obama's inaugural address and NEHA.

PMID- 19408427
TI  - Eating out: the business and the pleasure.

PMID- 19408428
TI  - Addressing climate change and local public health: the Austin Climate Protection
      Program and the CDC Working Group on Climate Change collaboration.

PMID- 19408429
TI  - Prevalence of Giardia and Cryptosporidium in muskrats in northeastern
      Pennsylvania and New Jersey.
AB  - Giardia spp. and Cryptosporidium spp. are intestinal parasites that affect humans
      and animals throughout the world. Although infection with Giardia spp. is usually
      self-limiting, some cases result in mild to severe enteritis. Giardiasis can be
      treated with modern drugs. The increasing incidence of well-documented outbreaks
      of Cryptosporidiosis has resulted in a growing awareness of the danger of this
      infection. In this study, the authors examined beavers and muskrats to determine
      their role as reservoir hosts in the spread of these two pathogens. The authors
      obtained fecal samples from trapped animals and examined them to detect
      simultaneously the presence of Cryptosporidium oocysts and Giardia cysts. Water
      samples collected from the trapping locations were also tested for the same
      pathogens. The study showed that 65.9% of the tested muskrats were positive for
      Giardia spp., 50% were positive for Cryptosporidium spp., and 29.3% were infected
      with both parasites. The surface water tests showed three sites were positive for
      Cryptosporidium spp. and none for Giardia spp. These findings suggest the muskrat
      may be an important reservoir host for both Cryptosporidium spp. and Giardia spp.

PMID- 19408430
TI  - The View-Master Health Study Focus Groups.

PMID- 19408431
TI  - Association between swimming pool operator certification and reduced pool
      chemistry violations--Nebraska, 2005-2006.
AB  - Previous studies have recommended mandatory education for all public pool
      operators, but substantiating data are limited. This study evaluates associations
      between pool operator certification and chemistry violations by using 2005-2006
      Nebraska routine pool inspection reports. Training and certification for
      nonmunicipal pool operators are only required in two Nebraska counties. Free
      chlorine violations for nonmunicipal pool inspections were compared in counties
      with and without certified operator requirements. To control for water supply pH,
      inspections from nonmunicipal pools with shared-source water in two counties (one
      requiring certification) were compared for concurrent pH and free chlorine
      violations. Compared with locations that require certified operators, free
      chlorine violations and concurrent pH and free chlorine violations were twice as
      likely in locations without certification. As a result, pools without required
      operator certification might pose greater health risks. These results demonstrate
      the benefit of requiring pool operator certification to help prevent recreational
      water illnesses.

PMID- 19408432
TI  - An evaluation of the effectiveness of the Gunderboom in protecting waters from
      bacteria.
AB  - Beaches located in the narrow inlet of Long Island Sound frequently contain high
      concentrations of bacteria. A Gunderboom BPS (Beach Protection System) filter was
      installed in Harbor Island Park of Mamaroneck Harbor, New York, in 2002 to reduce
      bacterial levels in the water. Water and sediment collected inside and outside
      the Gunderboom and other areas within Mamaroneck Harbor (Shore Acres Beach, Guion
      Creek, and Mamaroneck River) were tested for E. coli and total coliform bacteria
      and compared weekly from May through September 2006. The results showed that
      concentrations of E. coli and total coliform bacteria in water and sediment were
      significantly lower inside the Gunderboom when compared to the other sites. One
      third of the samples were collected within 48 hours of rainfall, and a positive
      correlation occurred between rainfall and bacterial levels in water. These
      results indicate the Gunderboom has the potential to reduce bacteria in both
      beach water and sediment.

PMID- 19408434
TI  - Dramatic changes in state legislatures.

PMID- 19408433
TI  - An observational study on the effectiveness of point-of-use chlorination.
AB  - Although the efficacy of chlorine disinfection under controlled laboratory
      conditions is well known, the effectiveness of chlorine under field point-of-use
      (POU) conditions is still not clearly understood and may be impacted by a variety
      of factors. This study evaluated the effectiveness of POU chlorine disinfection
      in rural Ecuador under typical use conditions and compared this effectiveness
      with the efficacy in controlled laboratory conditions. While reductions of
      indicator organisms were slightly higher in households that used chlorination, no
      significant differences were seen between households employing POU chlorination
      and the households with no chlorination (1-1.5 log10 median reductions for
      chlorinating households and 0.31-0.55 log10 for nonchlorinating households,
      depending on the indicator organism). In contrast, significant reduction of all
      test organisms was found when simulating POU conditions in the laboratory. This
      study demonstrates that POU chlorination can be considerably less effective under
      actual field conditions than would be predicted based on its laboratory efficacy
      (3-5 log10 median reductions for chlorinated and 0-0.3 log10 for nonchlorinated
      samples). Human factors (including improper storage and chlorine dosing) and
      uncontrolled water quality effects are hypothesized to impact significantly the
      effectiveness of chlorine disinfection.

PMID- 19408435
TI  - Abortion dilemma.

PMID- 19408436
TI  - Bushfires take toll on nurses.

PMID- 19408437
TI  - National Health and Hospitals Reform Commission report disappoints on workforce.

PMID- 19408438
TI  - Expand nurses' roles in primary health for indigenous people.

PMID- 19408439
TI  - EN takes on expanded role and is rewarded for excellence.

PMID- 19408440
TI  - Moral excellence and patient safety.

PMID- 19408441
TI  - Development and implementation of a 'nurse run' post acute stroke clinic.

PMID- 19408443
TI  - CATSIN welcomes national uniformity in nursing education.

PMID- 19408442
TI  - Research aims to improve remote area nursing in QLD.

PMID- 19408444
TI  - So much compassion in the face of great pain.

PMID- 19408446
TI  - Effect of delegation on standard of review. Geddes v. United Staffing, 469 F.3d
      919 (10th Cir. 2006).
AB  - When an ERISA plan administrator delegates his discretionary authority to render
      plan benefit decisions to a third party, even one that is not a fiduciary, de
      novo review is not triggered when litigation arises. Rather, the standard for
      review is the "arbitrary and capricious"standard as set by the US. Supreme
      Court's 1989 decision in Firestone Tire and Rubber Co. v. Bruch.

PMID- 19408445
TI  - Standard of review-effect of conflict on standard of review. Metropolitan Life
      Insurance Co. v. Glenn, _S. Ct._, 2008 WL 2444796 (6/19/08).
AB  - An ERISA plan administrator, whether it is an insurance company or a self-insured
      employer, has a conflict of interest if it both decides who receives benefits and
      makes benefits payments. That conflict of interest is one factor that should be
      taken into account in determining whether the administrator has abused its
      discretion in a case.

PMID- 19408447
TI  - Retiree health benefits--no emotional distress damages. Yolton v. El Paso
      Tennessee Pipeline Co., 2008 WL 275685 (E.D.Mich. 1/31/08).
AB  - Plaintiffs are not entitled to emotional distress damages under the Labor
      Management Relations Act (LMRA) when an employer breaches a collective bargaining
      agreement by failing to provide retiree health benefits. Plaintiffs may recover
      damages for the cost of replacement insurance incurred as a result of such a
      breach.

PMID- 19408448
TI  - Local health care initiatives--ERISA preemption of State Health Care Reform
      Health Insurance-Fair Share Act. Golden Gate Restaurant Association v. City and
      County of San Francisco, 512 F.3d 1112 (9th Cir. 2008).
AB  - A state or local ordinance is not preempted by ERISA if it does not bind plan
      administrators to structure plans in a certain way or mandate that they provide
      specific benefits to employees. A local law could be preempted if it contains
      specific provisions relating to ERISA, or the operation of the law itself depends
      upon ERISA.

PMID- 19408449
TI  - Efficient storage and transmission of digital fundus images with patient
      information using reversible watermarking technique and error control codes.
AB  - Handling of patient records is increasing overhead costs for most of the
      hospitals in this digital age. In most hospitals and health care centers, the
      patient text information and corresponding medical images are stored separately
      as different files. There is a possibility of mishandling the text file
      containing patient history. We are proposing a novel method for the compact
      storage and transmission of patient information with the medical images. In this
      technique, we are using a reversible watermarking technique to hide the patient
      information within the retinal fundus image. There is a possibility that these
      medical images, which carry patient information, can get corrupted by the noise
      during the storage or transmission. The safe recovery of patient information is
      important in this situation. So, to recover the maximum amount of text
      information in the noisy environment, the encrypted patient information is coded
      with error control coding (ECC) techniques. The performance of three types of ECC
      for various levels of salt & pepper (S & P) noise is tabulated for a specific
      example. The proposed system is more reliable even in a noisy environment and
      saves memory.

PMID- 19408450
TI  - Epileptic spike recognition in electroencephalogram using deterministic finite
      automata.
AB  - This Paper presents an automated method of Epileptic Spike detection in
      Electroencephalogram (EEG) using Deterministic Finite Automata (DFA). It takes
      prerecorded single channel EEG data file as input and finds the occurrences of
      Epileptic Spikes data in it. The EEG signal was recorded at 256 Hz in two minutes
      separate data files using the Visual Lab-M software (ADLink Technology Inc.,
      Taiwan). It was preprocessed for removal of baseline shift and band pass filtered
      using an infinite impulse response (IIR) Butterworth filter. A system, whose
      functionality was modeled with DFA, was designed. The system was tested with 10
      EEG signal data files. The recognition rate of Epileptic Spike as on average was
      95.68%. This system does not require any human intrusion. Also it does not need
      any short of training. The result shows that the application of DFA can be useful
      in detection of different characteristics present in EEG signals. This approach
      could be extended to a continuous data processing system.

PMID- 19408451
TI  - Primary care physician's attitude towards the German e-health card project-
      determinants and implications.
AB  - In Germany e-health cards will be distributed nationwide to over 80 million
      patients. Given the impending mandatory introduction of the e-health technology,
      the objective of this study was to examine the determinants of primary care
      physicians' acceptance of the technological innovation. The study was conducted
      prior to the introduction of the e-health cards. A questionnaire survey was
      carried out addressing primary care physicians from different fields. The
      reduction of medication error rates and the improvement of communication between
      medical caregivers are central aspects of the perceived usefulness. Primary care
      physicians rate their involvement in the process of the development of the
      technology and their own IT expertise concerning the technological innovation as
      rather low. User involvement and IT expertise can explain 46 % of the variance of
      perceived usefulness of the e-health card. User involvement plays a crucial role
      in the adoption of the German e-health card. Primary care physician's perspective
      should be represented in the process of developing and designing the technology.

PMID- 19408452
TI  - Comparison of short-time Fourier transform and Eigenvector MUSIC methods using
      discrete wavelet transform for diagnosis of atherosclerosis.
AB  - In this paper, a more effective use of Doppler techniques is presented for the
      purpose of diagnosing atherosclerosis in its early stages using the carotid
      artery Doppler signals. The power spectral density (PSD) graphics are obtained by
      applying the short-time Fourier transform (STFT)-Welch and the Eigenvector MUSIC
      methods to the discrete wavelet transform (DWT) of Doppler signals. The PSDs for
      the fourth approximation component (A4) of both methods estimated that the
      patients with atherosclerosis in its early phase had lower maximum frequency
      components. On the other hand, the healthy subjects had higher maximum frequency
      components. The area under the curve (AUC), which belongs to the receiver
      operating characteristic (ROC) curve for the frequency level of the maximum PSDs
      of the A4 approximation obtained from the STFT modeling, is computed as 0.97. The
      AUC for the MUSIC modeling is computed as 0.996. The AUC belonging to the ROC
      curve for the higher maximum frequency component is computed as 0.87. The AUC
      belonging to the ROC curve for the test parameter of the frequency level of the
      maximum PSDs derived from the MUSIC modeling is determined to be 0.882. The
      results of this study clearly demonstrate that it is possible to distinguish
      between the healthy people and the patients with atherosclerosis by using the
      frequency level of the maximum PSDs for the A4 approximation. Furthermore, it is
      concluded that the power of Eigenvector-MUSIC method in terms of the resolution
      of the high frequencies is better than that of the STFT methods.

PMID- 19408453
TI  - User satisfaction with computerized order entry system and its effect on
      workplace level of stress.
AB  - To evaluate the impact of Computerized Provider Order Entry (CPOE) on workplace
      stress and overall job performance, as perceived by medical students, housestaff,
      attending physicians and nurses, after CPOE implementation at Penn State-Milton
      S. Hershey Medical Center, an academic tertiary care facility, in 2005. Using an
      online survey, the authors studied attitudes towards CPOE among 862 health care
      professionals. The main outcome measures were job performance and perceived
      stress levels. Statistical analyses were conducted using the Statistical
      Analytical Software (SAS Inc, Carey, NC). A total of413 respondents completed the
      entire survey (47.9 % response rate). Respondents in the younger age group were
      more familiar with the system, used it more frequently, and were more satisfied
      with it. Interns and residents were the most satisfied groups with the system,
      while attending physicians expressed the least satisfaction. Attending physicians
      and fellows found the system least user friendly compared with other groups, and
      also tended to express more stress and frustration with the system. Participants
      with previous CPOE experience were more familiar with the system, would use the
      system more frequently and were more likely to perceive the system as user
      friendly. User satisfaction with CPOE increases by familiarity and frequent use
      of the system. Improvement in system characteristics and avoidance of confusing
      terminology and inconsistent display of data is expected to enhance user
      satisfaction. Training in the use of CPOE should start early, ideally integrated
      into medical and nursing school curricula and form a continuous, long-term and
      user-specific process. This is expected to increase familiarity with the system,
      reducing stress and leading to improved user satisfaction and to subsequent
      enhanced safety and efficiency.

PMID- 19408454
TI  - Analysis of normal human eye with different age groups using infrared images.
AB  - The human body temperature is a good health indicator. All objects emit thermal
      radiation as a function temperature and wavelength for all wavelengths. The
      wavelength of infrared rays lies between visible and microwave radiations ranging
      between 700 nm to 0.1 mm. Infrared (IR) imaging is relatively inexpensive,
      noninvasive and harmless. Nowadays, it is widely used in the medical field for
      diagnosis. In this work, we have applied image processing techniques on the IR
      images of the eye for the analysis of the ocular surface temperature (OST) of the
      normal subjects of three categories (young, middle and old ages). In our study,
      67 IR normal images were analyzed. Two parameters, average ocular temperature and
      the temperature deviation were proposed to study the variability of OST in
      different normal category subjects. Our study shows that, the two parameters
      proposed, show distinct ranges for different groups with 'p' values less than
      0.05.

PMID- 19408456
TI  - Health information exchange and healthcare utilization.
AB  - Health information exchange (HIE) makes previously inaccessible data available to
      clinicians, resulting in more complete information. This study tested the
      hypotheses that HIE information access reduced emergency room visits and
      inpatient hospitalizations for ambulatory care sensitive conditions among
      medically indigent adults. HIE access was quantified by how frequently system
      users' accessed patients' data. Encounter counts were modeled using zero inflated
      binomial regression. HIE was not accessed for 43% of individuals. Patient factors
      associated with accessed data included: prior utilization, chronic conditions,
      and age. Higher levels of information access were significantly associated with
      increased counts of all encounter types. Results indicate system users were more
      likely to access HIE for patients for whom the information might be considered
      most beneficial. Ultimately, these results imply that HIE information access did
      not transform care in the ways many would expect. Expectations in utilization
      reductions, however logical, may have to be reevaluated or postponed.

PMID- 19408455
TI  - How to effectively implement an indicator system to improve performance from a
      management perspective: the case of Taiwan Healthcare Indicator Series (THIS)
      system.
AB  - This study uses the Taiwan Healthcare Indicator Series (THIS) system as an
      example to examine which determinants would improve performance by sharing
      indicators from a management perspective. This study population included all 227
      hospitals participating in the THIS system in 2006. A structured questionnaire
      was sent to the director who was responsible for the THIS system via electronic
      mail. A total of 111 responses were returned by February 10, 2006. Questions
      included current implementation and impacts of the system. Hierarchical
      regression models were performed to identify which variables were significantly
      associated with performance improvement, adjusted for hospital characteristics.
      Four variables significantly associated with implementing the THIS system to
      improve performance were 'senior management support,' 'benchmarking,' 'making
      departments improve the underperforming indicators and report the improvement
      results in performance management meetings,' and 'integration with the National
      Health Insurance payment regulations'. This study contributes substantially to
      the evidence base about what works to improve performance by information sharing.
      Although information sharing is the basis of efforts to improve performance,
      senior management support and how to effectively apply the information are the
      most important determinants of performance enhancement.

PMID- 19408457
TI  - A simulation approach for scheduling patients in the department of radiation
      oncology.
AB  - Physical therapy, hemodialysis and radiation oncology departments in which
      patients go through lengthy and periodic treatments need to utilize their limited
      and expensive equipment and human resources efficiently. In such departments, it
      is an important task to continue to treat current patients without any
      interruption along with incoming patients. In this study, a patient scheduling
      approach for a university radiation oncology department is introduced to minimize
      delays in treatments due to potential prolongations in treatments of current
      patients and to maintain efficient use of the daily treatment capacity. A
      simulation analysis of the scheduling approach is also conducted to assess its
      efficiency under different environmental conditions and to determine appropriate
      scheduling policy parameter values. Also, the simulation analysis of the
      suggested scheduling approach enables to determine appropriate scheduling
      parameters under given circumstances. Therefore, the system can perform more
      efficiently.

PMID- 19408459
TI  - Counteracting the effects of chemosensory dysfunction.

PMID- 19408458
TI  - Taste and odor abnormalities in cancer patients.
AB  - Taste and odor abnormalities are major daily concerns for patients with cancer.
      This review summarizes the common taste and odor disorders of cancer patients and
      provides insight into their possible causes. Cancer and its therapy, including
      chemotherapy and radiotherapy, may directly alter and damage taste and odor
      perception.These alterations affect the daily quality of life of these patients
      and may lead to patient malnutrition and, in severe cases, significant morbidity.
      Cancer patients experience decreases in sensitivity to taste and odor, as well as
      unpleasant metallic and bitter sensations. Complaints relating to taste and odor
      are not usually addressed, as few, if any, effective interventions are available
      for these problems. Understanding the types and causes of taste and odor
      dysfunctions will enable researchers and physicians to develop treatments for
      these conditions and thereby improve patient quality of life.

PMID- 19408460
TI  - Taste and smell alterations in cancer patients--real problems with few solutions.

PMID- 19408461
TI  - The relationship between taste, olfaction, and nutrition in the cancer
      population.

PMID- 19408462
TI  - 1958-2008: 50 years of youth fitness tests in the United States.
AB  - The AAHPER Youth Fitness Test, the first U.S. national fitness test, was
      published 50 years ago. The seminal work of Krause and Hirschland influenced the
      fitness world and continues to do so today. Important youth fitness test
      initiatives in the last half century are summarized. Key elements leading to
      continued interest in youth fitness testing at the start of the 21st century
      include (a) concerns about children and youth fitness levels, (b) AAHPER(D)-led
      youth fitness battery development, (c) differentiation between performance
      related and health-related fitness testing, (d) the numerous youth fitness tests
      developed, (e) collaborative discussions on development and adoption of a unified
      national youth fitness battery, (f) computerization of youth fitness test
      results, (g) differentiation between norm-referenced and criterion-referenced
      evaluation of student results, and (h) concern about youth fitness levels (again,
      but with a focus on health). We have come full circle on youth fitness interests.
      This article summarizes the key youth fitness tests in the second half of the
      20th century and projects future considerations.

PMID- 19408464
TI  - Decreasing sports activity with increasing age? Findings from a 20-year
      longitudinal and cohort sequence analysis.
AB  - According to cross-sectional studies in sport science literature, decreasing
      sports activity with increasing age is generally assumed. In this paper, the
      validity of this assumption is checked by applying more effective methods of
      analysis, such as longitudinal and cohort sequence analyses. With the help of 20
      years' worth of data records from the German SocioEconomic Panel, the development
      of sports activity over a lifespan is analyzed. According to inadequate cross
      sectional analyses, sports activity decreases with increasing age. In contrast,
      longitudinal analyses show that sports activity increases with increasing age.
      Furthermore, cohort sequence analyses indicate that not only age but also cohort
      and period effects influence sports activity. Thus, different methods of analysis
      reveal opposite results.

PMID- 19408463
TI  - Health worry, physical activity participation, and walking difficulty among older
      adults: a mediation analysis.
AB  - This study examined the effect of health worry (i.e., cognitive aspect of anxiety
      resulting from concern for health) on walking difficulty in a nationally
      representative sample (N = 7,527) of older adults (M age = 76.83 years). The
      study further tested whether physical activity mediates the effect of health
      worry on walking difficulty in a 6-year follow-up design. Results of a mediation
      analysis using structural equation modeling showed that people with a high degree
      of health worry engaged in less physical activity (beta = -.24, p < .001), and
      people who participated in less physical activity were more likely to report
      walking difficulty at the 6-year follow-up (beta = -.22, p < .001). There was a
      significant indirect effect from health worry to walking difficulty through
      physical activity (beta = .05, p < .001), controlling for demographic,
      psychosocial, and health related factors. Results suggested that inducing threat
      and worry may not be effective for physical activity promotion in the older
      population. More promising coping and regulation strategies are discussed.

PMID- 19408465
TI  - Conditions of practice in perceptual skill learning.
AB  - This study uses three experiments with different kinds of training conditions to
      investigate the "easy-to-hard" principle, context interference conditions, and
      feedback effects for learning anticipatory skills in badminton. Experiment 1 (N =
      60) showed that a training program that gradually increases the difficulty level
      has no advantage over the randomized variant. Experiment 2 (N = 60) pointed out
      that when comparing the blocked (lateral before depth dimension) perceptual
      training group with the random perceptual training group a significant advantage
      for the random group was found in the retention test (depth error). Experiment 3
      (N = 40) demonstrated that training with reduced feedback (66 %) is no more
      effective than 100% feedback training in a group of novice performers.

PMID- 19408466
TI  - Effects of teacher autonomy support and students' autonomous motivation on
      learning in physical education.
AB  - This study applied self-determination theory to investigate the effects of
      students' autonomous motivation and their perceptions of teacher autonomy support
      on need satisfaction adjustment, learning achievement, and cardiorespiratory
      fitness over a 4-month personal conditioning unit. Participants were 253 urban
      adolescents (121 girls and 132 boys, ages = 12-14 years). Based on a series of
      multiple regression analyses, perceived autonomy support by teachers
      significantly predicted students'need satisfaction adjustment and led to learning
      achievement, especially for students who were not autonomously motivated to learn
      in physical education. In turn, being more autonomous was directly associated
      with cardiorespiratory fitness enhancement. The findings suggest that shifts in
      teaching approaches toward providing more support for students' autonomy and
      active involvement hold promise for enhancing learning.

PMID- 19408467
TI  - Ice hockey players using a weighted implement when training on the ice: a
      randomized control trial.
AB  - The purpose of this study was to investigate the potential for improving hockey
      players'performance using a weighted implement on the ice. Forty-eight players
      were tested using a grip strength dynamometer They also were assessed on their
      abilities to stick-handle. The participants were randomly placed into a control
      or research group. The conditioning drills were performed for 10-15 min 3
      days/week for 6 weeks. Use of the weighted implement resulted in a significantly
      enhanced grip strength endurance and stick-handling ability (p < .05). Using
      weighted implements prior to a regular ice hockey training session may be of
      benefit to young hockey players to enhance their grip strength endurance and
      stick-handling abilities.

PMID- 19408468
TI  - No change of body mass, fat mass, and skeletal muscle mass in ultraendurance
      swimmers after 12 hours of swimming.
AB  - We evaluated whether ultraendurance swimmers suffer a change of body mass, fat
      mass, skeletal muscle mass, total body water and specific gravity of urine during
      a 12-hr swim in 12 male Caucasian ultraswimmers. Proton nuclear magnetic
      resonance of urine samples before and after the race was performed to detect
      alanine, lactate, and 3-hydroxybutyrate. The 12 swimmers achieved an average
      distance of 29.4 km (SD = 5.1). No statistically significant changes in body
      mass, fat mass, skeletal muscle mass, and total body water could be determined (p
      > .05), but urine gravity decreased significantly (p < .001). Two participants
      showed increased signals of ketone bodies after the race. In these samples, the
      hydroxybutyrate-creatinine ratio increased more than tenfold.

PMID- 19408469
TI  - Comparison of heart rate response to tennis activity between persons with and
      without spinal cord injuries: implications for a training threshold.
AB  - The purpose of this study was to evaluate the ability of individuals with spinal
      cord injury (SCI) to reach a training threshold during on-court sport activity.
      Monitors collected heart rate (HR) data every 5 s for 11 wheelchair tennis
      players (WCT) with low paraplegia and 11 able-bodied controls matched on
      experience and skill level (ABT). Average HR was determined for time spent in
      practice (e.g, drills) and game (i.e., a competitive set), and the ability to
      surpass 50% peak HR (HRpeak) and 64% HRpeak in each condition was evaluated.
      Average exercise intensity (%HRpeak) was not significantly different between the
      groups during practice (M WCT = 68.18, SD = 7.53%, M ABT = 68.78, SD = 5.44%; t =
      .22, p = .83) or game (M WCT = 68.17, SD = .17%, M ABT = 71.55, SD = 4.75%; t =
      1.12, p =.28). Allparticipants averaged an intensity > or = 50% HR-peak during
      practice and game, and the difference between group participants averaging an
      intensity > or = 64% HRpeak was not significant during practice (chi2 = .92, p =
      .34) or game (chi2 = 3.85, p = .05). In terms of reaching a health and fitness
      training threshold during tennis, individuals with low-level SCI are similar to
      matched controls.

PMID- 19408470
TI  - Exploring the relationship between exercise-induced arousal and cognition using
      fractionated response time.
AB  - Although a generally positive effect of acute exercise on cognitive performance
      has been demonstrated, the specific nature of the relationship between exercise
      induced arousal and cognitive performance remains unclear This study was designed
      to identify the relationship between exercise-induced arousal and cognitive
      performance for the central and peripheral components of a response time task at
      two different levels of task difficulty. Sixteen male participants performed both
      simple and choice response time tasks at eight different arousal levels (from 20%
      to 90% heart rate reserve). Performance on the simple and choice response time
      tasks was examined after fractionating the response time into its central
      component, premotor time, and peripheral components, motor, and movement time. A
      priori trend analysis was used to test both linear and quadratic relationships.
      Results indicated that exercise-induced arousal has a positive influence on the
      peripheral components of response time tasks; however it has a limited impact on
      the central components of these tasks.

PMID- 19408471
TI  - Preadolescent female development through sport and physical activity: a case
      study of an urban after-school program.
AB  - Youth development research has found that children become more engaged and
      benefit more from being incorporated as decision makers. Thus participation helps
      promote development and encourages engagement. Based in theories of engagement
      and free-choice learning, the current research focused on a program combining
      sport/physical activity, life skills, and mentoring while promoting healthy life
      choices for preadolescent girls of color The co-investigators, all women,
      conducted two 2-hr visits per week for two 12-week periods with a group of 8
      girls at a community recreation center in Hartford, Connecticut, including
      lessons in nutrition and life skills and participation in a sport/physical
      activity. Five of the girls completed every stage of data collection, including
      participant journals and four individual interviews with each participant and her
      parents, over the course of the 24 weeks. The co-investigators also kept journals
      throughout the program. The results reflected the following themes: self
      esteem/self-worth, accountability/responsibility for self connections to
      community and a sense of belonging, knowledge and acquisition of health/life
      skills, application of those skills, and planning and recognizing one's own
      influence on self and others.

PMID- 19408472
TI  - African American football athletes' perspectives on institutional integrity in
      college sport.
AB  - This qualitative case study used tenets of critical race theory and a single
      focus group and individual interviews with 4 African American football athletes
      at a predominantly White institution of higher education (PWIHE) in an effort to
      bring the voices of this marginalized group into the dialogue on issues
      concerning institutional integrity in college sport. Institutional integrity
      involves an athletic program's actual commitment to the educational interests of
      college athletes as expressed through their structures, functions, and
      activities. Three themes emerged from the data: (a) there is a need for more
      African American role models in leadership positions within the athletic
      departments of these PWIHE; (b) there is a need for more financial support for
      athletes; and (c) African American athletes should be given a platform to voice
      concerns. These findings have implications for those educational stakeholders and
      researchers who are genuinely concerned with institutional integrity in college
      sport.

PMID- 19408473
TI  - Factorial validity and gender invariance of the physical activity enjoyment scale
      (PACES) in older adolescents.

PMID- 19408474
TI  - Ability beliefs, task value, and performance as a function of race in a dart
      throwing task.

PMID- 19408476
TI  - The effect of interimplant distance on the height of the interimplant bone crest
      when using platform-switched implants.
AB  - A distance of more than 3 mm between two adjacent standard implants has been
      shown to preserve the interproximal bone peak, resulting in only 0.45 mm of
      resorption. The purpose of this study was to determine whether use of the
      platform-switching technique would change the bone resorption patterns between
      adjacent implants placed less than 3 mm apart. Radiographic studies of bone
      resorption around 41 pairs of implants placed less than 3 mm apart in 37 patients
      were carried out. Mean vertical bone resorption was 0.62 mm, and the mean
      horizontal component was 0.60 mm. The bone peak that extended coronally beyond an
      imaginary line connecting the two implant-abutment interfaces was measured, and
      the mean bone height preservation above this interimplant line was 0.24 mm.

PMID- 19408475
TI  - Human histologic evaluation of mineralized collagen bone substitute and
      recombinant platelet-derived growth factor-BB to create bone for implant
      placement in extraction socket defects at 4 and 6 months: a case series.
AB  - The objective of this pilot study was to assess whether mineralized collagen bone
      substitute (MCBS) combined with recombinant human platelet-derived growth factor
      BB (0.3 mg/mL) would generate adequate viable bone in buccal wall extraction
      defects to accommodate implant placement. The primary outcome variable was bone
      quality, as measured by microcomputed tomography and histologic evaluation. This
      was successfully accomplished in all eight specimens obtained from seven
      patients. The secondary outcome variables were bone quality and quantity as
      observed clinically, radiographically, and by the primary stability of implants
      at the time of placement. Soft tissue healing was excellent, and there were no
      unanticipated adverse events. Robust bone formation accompanied by MCBS
      resorption was evident in all 4- and 6-month specimens. This was accomplished
      without barrier membranes.

PMID- 19408477
TI  - Flap design for guided tissue regeneration surgery in the esthetic zone: the
      "whale's tail" technique.
AB  - The aim of this paper was to describe a new surgical technique designed to
      preserve interdental tissue in guided tissue regeneration. This procedure was
      created to specifically regenerate wide intrabony defects in the esthetic zone.
      Fourteen subjects with an intraosseous defect in the maxillary incisor region
      took part in this clinical study. The defects were treated with bioresorbable
      membranes in combination with a bovine bone mineral graft. At baseline and at 12
      months after surgery, the following clinical parameters were measured: full-mouth
      plaque scores, full-mouth bleeding scores, probing pocket depths, clinical
      attachment levels, and gingival recession. A significant gain in clinical
      attachment level (4.57 +/- 0.65 mm) and a reduction in probing depths (5.14 +/-
      0.95 mm) were reported 12 months after surgery. The surgical technique allowed
      complete flap closure in every treated site, resulting in significant improvement
      of the clinical parameters; thus, it appeared especially appropriate for the
      treatment of wide defects in the esthetic zone.

PMID- 19408478
TI  - Tapered implants: from indications to advantages.
AB  - Tapered implants have become routine for immediate implant placement after tooth
      extraction. It seemed extremely advantageous to use tapered implants in type 4
      bone, where primary stability is difficult to achieve. The authors established a
      surgical implant placement protocol to be followed in areas where type 4 bone and
      a wide bone ridge (> or = 8 mm) are present. First, preparation of the implant
      alveolus is done exclusively with cylindric osteotomes, rather than with conic
      osteotomes or drills. The final cylindric osteotome is the same diameter as the
      final twist drill that is typically used in conventional preparation of the
      implant alveolus (a technique that can be adapted for use with other tapered
      implants). Because of the self-tapping property of the tapered implant used and
      its anatomic design, this surgical technique was developed to optimize the bone
      compaction effect in the coronal third of the implant, improving bone density and
      providing better primary stability values (> or = 70 ISO, via the Osstell Mentor
      device). With the strong bond that is created between the implant surface and the
      surrounding bone using this technique, immediate loading can be predictable, even
      in the type 4 bone that is commonly found in the maxillary tuberosity.

PMID- 19408479
TI  - Histological and clinical evaluation of recombinant human platelet-derived growth
      factor combined with beta tricalcium phosphate for the treatment of human Class
      III furcation defects.
AB  - Four patients with chronic advanced periodontitis participated in this study. At
      least one mandibular first molar had to have a hopeless periodontal and
      prosthetic prognosis. Clinical measurements were made, and the furcation defects
      were surgically exposed. A notch was placed through the calculus on both the
      mesial and distal roots. The furcal area was root planed with diamond-tip
      ultrasonic instruments. The furcations were grafted with a combination of
      recombinant human platelet-derived growth factor and beta tricalcium phosphate. A
      collagen barrier for guided tissue regeneration was used on both the facial and
      lingual surfaces. The flaps were coronally positioned and sutured. All patients
      were followed at 2-week intervals for 6 months. At 6 months, all teeth
      demonstrated a reduction in probing depth and a gain in clinical attachment. One
      tooth demonstrated a Class II furcation involvement, while through-and-through
      furcation involvement was still evident on the other three experimental teeth.
      The teeth were removed en bloc and processed for histologic evaluation. Three
      root surfaces demonstrated periodontal regeneration, an additional three showed
      new attachment, and one surface revealed junctional epithelium as measured from
      the base of the calculus notch. The notch area could not be identified on one
      surface of one specimen.

PMID- 19408480
TI  - A comparative study of two root-coverage techniques with regard to interdental
      papilla dimension as a prognostic factor.
AB  - This study was designed to evaluate the effectiveness of subepithelial connective
      tissue graft (SCTG) and acellular dermal matrix allograft (ADMA) in root coverage
      procedures and to examine the effect of interdental papilla dimensions on the
      outcome of root coverage using a new approach. This randomized controlled
      clinical study included 32 gingival recession defects of at least 2 mm classified
      as Miller Class I or II. Clinical parameters were measured at baseline and 6, 12,
      and 24 weeks postsurgery. At baseline, all measured clinical parameters were
      statistically equivalent between the two groups. With regard to the amount of
      mean root coverage, no significant difference was found between ADMA (85.42%) and
      SCTG (69.05%) groups. However, the percentage of complete root coverage was
      significantly greater in the ADMA group (75.0%, versus 31.3% in the SCTG group).
      Significant positive correlations were found between papilla height and papilla
      width and mean root coverage, and papilla height of at least 5 mm was associated
      with complete root coverage. ADMA seems to be a good substitute for SCTG to treat
      shallow to moderate gingival recessions. In addition, papilla dimensions, as
      measured using the new method, can help predict the success of future root
      coverage.

PMID- 19408481
TI  - Use of sintered porous-surfaced dental implants to restore single teeth in the
      maxilla: a 7- to 9-year follow-up.
AB  - This report from a prospective study discusses the status of a group of 20 single
      maxillary sintered porous-surfaced (SPS) dental implants after 7 to 9 years in
      function restored with screw-retained crowns. Twenty patients each received a
      single SPS implant placed in a two-stage surgical approach; 65% replaced premolar
      or molar teeth, while the remainder replaced anterior teeth. Patients were
      examined annually. Standardized radiographs were used to assess peri-implant
      crestal bone levels and to determine an implant success rate. Jemt Papilla Index
      scores were used to assess the extent of papilla reformation between each implant
      and its two contiguous teeth. After 7 to 9 years, 17 implants were available for
      assessment (one patient had died, and two patients had moved away). One implant
      was removed after the 9-year visit because of progressive bone loss, giving a
      survival rate of 92.9%. The failure of this implant was related to deficiency in
      initial alveolar ridge width with loss of the remaining thin buccal cortical
      plate. With the exception of the failed implant, no significant changes in mean
      annual crestal bone loss were noted from years 1 to 9, giving a similar success
      rate (92.9%). Jemt Papilla Index scores of 2 or 3 were assigned for the majority
      of papillae. SPS implants can be used effectively to replace single missing
      maxillary teeth.

PMID- 19408482
TI  - Efficacy of the supraperiosteal envelope technique: a preliminary comparative
      clinical study.
AB  - The purpose of this clinical study was to compare the effectiveness of the
      supraperiosteal envelope technique as performed by three surgeons with different
      amounts of professional experience during a 6-month observation period. Sixty
      eight gingival recessions in 35 healthy patients were selected and included in
      clinical recordings. They were statistically evaluated at baseline and 6 months
      later. First, clinical parameters (attachment level, pocket depth, recession
      height, recession width, and gingival keratinized tissue height) were calibrated
      between the three operators. Then, single or multiple gingival recessions were
      selected and surgical techniques were standardized by the surgeons (A, B, C). The
      root coverage percentages obtained by the three operators were 81% for operator
      A, 85% for operator B, and 89% for operator C, for an average of 85%; initial
      recession height values were 2.5 mm (A), 4.3 mm (B), and 4.4 mm (C). The
      preliminary results of this trial showed the capacity of this surgical technique
      to provide favorable clinical benefits irrespective of the initial dimensions of
      recession-type defects and irrespective of the learning curve and experience of
      operators.

PMID- 19408484
TI  - Ethical problems in burn medicine.

PMID- 19408483
TI  - Tunnel technique for the treatment of impacted mandibular canines.
AB  - The tunnel technique is a combined therapeutic approach that includes both
      surgical exposure of the impacted canine and orthodontic traction of the tooth to
      the center of the alveolar ridge, followed by final orthodontic alignment. A
      healthy periodontium at the completion of therapy is the expected outcome. The
      tunnel technique has been shown to be effective in the treatment of impacted
      maxillary canines and can be suggested for the treatment of infraosseous impacted
      canines in the mandible when the corresponding primary canine is still present.
      Through the description of clinical cases, the management of the tunnel technique
      is reported.

PMID- 19408485
TI  - Late complication of respiratory thermal injuries.
AB  - Inhalation injury with severe burns is a most complex injury, and despite so much
      progress in therapy, resuscitation and ventilation it still has high mortality.
      The mortality rate is over 30%, depending on surface burns and complications.
      This paper is designed to present late complications and respiratory impairment
      in patients with severe thermal injury. Retrospective study of 51 patients from
      the years 2006 and 2007 evaluated late complications of the thermal lung
      injuries. Of 147 patients admitted to the Intensive care Unit (ICU), 51 had
      different type of inhalation injury as established by bronchoscope. All patients
      with inhalation injury had ventilatory support. None of the patients had pre
      existing lung disease prior to injury. The patient demographic data was as
      follows: 48 male, 3 female patients; varying age from 6 to 79 years, mean TBSB 57
      +/- 23%; mean third degree burns 42 +/- 18%; 11 patients had severe inhalation
      injury diagnosed by bronchoscopy and CT scan. The mortality rate was 45.1%.
      Bronchopneumonia was the most frequent complication, found in 92% of patients (46
      patients). Fluidothorax was present in 20% of patients (11 patients), 36% of
      patients had ARDS (13 patients), and 5.8% (3 patients) had tracheoesophageal
      fistula.

PMID- 19408486
TI  - Enzymatic necrolysis of acute deep burns--report of preliminary results with 22
      patients.
AB  - Enzymatic debridement by the use of a proteolytic enzyme complex derived,
      isolated and purified from pineapple stems proves to be an innovative, rapid,
      effective, selective and safe method of postburn necrotic skin removal. The major
      advantages of the procedure include minimal invasivity, rapidity, effectiveness,
      possibility to perform the debridement at the bedside, minimal or no loss of
      blood and minimal interference with natural wound healing processes. Our
      preliminary experience with this treatment method showed that in most of the
      cases treated the debridement was excellent, safe and rapid. The average duration
      of the debridement was less than 4 hours. The debridement was accompanied by
      minor to moderate pain which could be treated by analgetic medications. No
      serious adverse events or reactions have been observed during the study. The time
      for healing was comparable with the standard of care methods. The second
      randomized multicenter study is still in progress and has not yet been finished.

PMID- 19408489
TI  - We need more nurses, specialists agree.

PMID- 19408488
TI  - Daring to blow the whistle.

PMID- 19408487
TI  - Hemocoagulation disorders in extensively burned patients: pilot study for scoring
      of the DIC.
AB  - GOAL OF THE STUDY: To apply results of the hemocoagulation parameters to the DIC
      (disseminated intravascular coagulation) score system. Compare parameters of the
      DIC score in patients with extensive burn trauma (hospitalized at the Intensive
      Care Unit, ICU) and patients with lesser extent of burn injury (hospitalized at
      the standard unit). To use these data within the evidence based medicine for the
      prediction of organ damage and multi-organ failure. TYPE OF STUDY: Prospective
      study. MATERIAL AND METHODS: We have included total of 36 patients in the group
      within four months. Twelve patients were hospitalized at the ICU, 24 patients
      were hospitalized at the intermedial care and standard unit. Repeatedly, we have
      taken blood from patients to evaluate the hemocoagulation parameters. In patients
      hospitalized at the ICU, the blood was taken from the central vein (prior to the
      drawn, the access was flushed with 100 ml of F1/1, the blood was taken from
      different access than from the one administering heparin), in patients
      hospitalized at the standard unit the blood was taken from a peripheral vein. The
      results were then put into the tables established according to the ISTH
      (International Society on Thrombosis and Hemostasis). Next, the DIC score was
      calculated to predict severity of hemocoagulation balance disorders in burn
      trauma, or occurrence of complications during the treatment. RESULTS: Part 1: We
      have evaluated 12 patients (4 females) hospitalized at the ICU. At the day of
      injury the overt DIC score reached 1.25 (0-3), fifth day after the injury the
      average value of overt DIC score was 1.83 (0-3), one day after the
      autotransplantation it was 2.08 (0-3) and at the day of discharge from the
      hospital 0. In the deceased patient the DIC score reached value of 2. Part 2: We
      evaluated 24 patients (10 females) hospitalized at the standard unit. The extent
      of their burn injury was 5.9% TBSA (0.5-12% TBSA), age 49.13 years (17-94 years).
      At the day of injury the overt DIC score reached 0.25 (0-2). Fifth day after the
      injury the average value of overt DIC score was 1.66 (0-2). Day after the
      autotransplantation it was 1.83 (0-3) and at the day of discharge 0.02 (0-2).
      CONCLUSION: During the treatment of the patients with various extent of burn
      injury, none of the patients' scores reached values that would mean occurrence of
      obvious "overt" DIC.

PMID- 19408490
TI  - One baby, one nurse.
AB  - Bliss is campaigning for more neonatal nurses to meet the one-to-one care
      standard for premature and sick babies.

PMID- 19408491
TI  - A bigger picture.
AB  - From April 1, the Care Quality Commission takes over responsibility from three
      existing commissions for regulation of health and social care in England.

PMID- 19408492
TI  - Be ready to fight.

PMID- 19408493
TI  - Mentoring students: establishing effective working relationships.
AB  - Half of nurses' pre-registration training comprises practice placements, on which
      qualified nurses act as mentors. Standards for professional practice relating to
      mentoring nursing students are mandatory and set by the Nursing and Midwifery
      Council. They include: establishing effective working relationships through
      placement orientation; facilitating and evaluating learning, assessment and
      accountability; creating an environment conducive to learning; and ensuring
      students understand the importance of the context of practice, evidence-based
      practice and leadership. This article discusses related and interdependent
      aspects of mentoring that are essential for successful practice placements.

PMID- 19408494
TI  - Measuring health-related quality of life in cancer patients.
AB  - The measurement of health-related quality of life (HRQoL) is being increasingly
      advocated in healthcare practice, particularly in relation to cancer care. The
      use of patient-reported health instruments has been recommended in Lord Darzi's
      review of the NHS. Consequently, nurses have to be aware of the most reliable and
      valid QoL measurement tools for given situations and conditions. The aim of this
      article is to review the most common HRQoL tools for use in the oncology setting,
      highlighting the specific properties of each instrument.

PMID- 19408495
TI  - A guide to commissioning in the NHS and its effects on clinical care.
AB  - Commissioning in the NHS involves identifying the needs of a local population and
      then planning and funding care to meet those needs. This article gives an
      overview of the commissioning process and its effect on clinical care.

PMID- 19408497
TI  - Love it or loathe it.

PMID- 19408496
TI  - Compression therapy.

PMID- 19408498
TI  - Prepare to be moved.

PMID- 19408499
TI  - Is ethmoidal adenocarcinoma screening in employees exposed to wood dust
      justified?
AB  - INTRODUCTION: Since 1995, the means which are used for the follow-up of wood
      workers in France are obsolete. Based on experts' opinions, they have never been
      assessed as effective in the detection of adenocarcinoma of the ethmoid sinus.
      OBJECTIVE: Collecting the data present in the literature to justify the necessity
      and the means of a screening protocol that would help detect ethmoidal
      adenocarcinoma among the wood worker population. METHOD: This is a review of the
      literature from three data bases: the National Library of Medicine, the French
      National Institute for Research and Security and the French National Centre for
      Scientific Research. Only English and French articles were reviewed and they were
      classified in four categories according to proof tools purposed by the French
      High Authority for Health. RESULTS: There is a direct statistical relationship
      between the amount of wood dust and the development of ethmoidal adenocarcinoma,
      but threshold doses cannot actually be calculated. The relative risk is high
      starting the first year of exposure and the exposed population is well
      recognized. Despite the means presently available for follow-up, this lesion is
      always diagnosed at an advanced stage. Survival rates at 5-years would increase
      if the tumour were to be detected at stages T1 or T2. The CT scan is not suited
      for this aim because of its low sensibility in separating soft tissue contrast.
      On the other hand, the MRI allows the detection of small nasal or sino-nasal
      tumours with intact osseous boundaries with a 98% sensibility. However, the data
      from experimental models and healthy human volunteers show that wood-dust settles
      over the olfactory cleft and the adjacent mucosa. Moreover in the large majority
      of cases the implantation pedicle of these tumours is coming from within these
      areas. Therefore, nasal fibroscopic examination represents the best tool to
      detect adenocarcinoma of the ethmoid sinuses at its earlier stages. It is well
      tolerated and its cost is low. CONCLUSION: A screening of ethmoidal
      adenocarcinoma seems to be possible with simple means in specific population. An
      early detection could improve the prognosis of this lesion.

PMID- 19408500
TI  - Anterior cerebrospinal fluid leaks in children and adults: five years experience.
AB  - OBJECTIVES: To describe surgical experience in the repair of anterior skull base
      defects, we studied patients with congenital or acquired defects. According to a
      multidisciplinary evaluation, all subjects underwent surgery performed by an ENT
      surgeon in order to avoid craniotomy. DESIGN: Retrospective study of patients who
      were treated for an anterior skull base defect between 2000 and 2005 at a
      tertiary referral centre. MATERIALS AND METHODS: Twelve patients had surgery to
      correct anterior skull base defects. Four patients had spontaneous anterior basal
      defect and eight had a post-traumatic cerebrospinal fluid (CSF) leakage. The
      diagnosis was made with imaging studies: Computed Tomography (CT) and Magnetic
      Resonance Imaging (MRI) scans, possibly supplemented by a cisternography. The
      defects were repaired using the endoscopic endonasal approach excepted in frontal
      sinus location. RESULTS: CT and MRI scans demonstrated the defect in all but two
      cases. In one of them, MR cisternography showed the intranasal sac and in the
      other CT cisternography demonstrated a CSF fistula without any bone defect at the
      ethmoid roof. After surgery, the follow-up period was at least 16 months (mean 26
      months). Success rate at first attempt was 83%. Two adults needed a second
      surgical repair with successful outcome in one, increasing the success rate to
      92% after the second attempt. One female patient, obese with a body mass index >
      30 and hydrocephaly, had a recurrence of CSF leakage despite surgical revision.
      Postoperative imaging studies, CT scan or MRI, showed that the defect had
      successfully been repaired in 11 patients. CONCLUSION: High-resolution CT scan,
      MRI with or without cisternography, should investigate osteo-meningeal defect.
      Our report confirms that endonasal surgical techniques are useful for treating
      meningoceles and meningo-encephaloceles. The external route is to be preferred
      when the lesion is located in the apex of the frontal sinus.

PMID- 19408501
TI  - [Medical rhinoplasty: rationale for atraumatic nasal modelling using botulinum
      toxin and fillers].
AB  - OBJECTIVES: To describe the new techniques for medical rhinoplasty, associating
      fillers and botulinum toxin without invasive surgery, to evaluate their
      efficiency with a retrospective analysis on 85 patients for 2 years, and to
      discuss the adequate indications for this new approach. MATERIAL AND METHODS:
      Between january 2006 and january 2008, 85 patients were treated using a non
      surgical approach for aesthetic disorders of the nasal pyramid. 62 women and 23
      men were included, with different indications: 32 primary rhinoplasties, 53
      secondary rhinoplasty corrections. Fillers were used alone in 58 cases, botulinum
      toxin alone in 12 cases, and both products were used together in 15 cases.
      Botulinum toxin was always an A-type toxin. For fillers, reticulated hyaluronic
      acid was used in 56 cases, calcium hydroxyapatite in 11 cases, tricalcium
      phosphate in 2 cases, L-polylactic acid in 2 cases and polyacrylamid gel in 2
      cases. Fillers were injected after application of anaesthetic gel, and placed in
      depth with osteocartilaginous contact following a retro-tracing movement. At the
      end of the procedure, the nose was manually modelled in order to improve the
      product distribution. Botulinum toxin injection was performed without anaesthesia
      following a specific protocol. Clinical results were evaluated by the patient and
      the physician immediately after treatment, after 15 days and after 1 month. The
      satisfaction index was based on 3 answers after 1 month: very satisfactory,
      satisfactory, insufficient. RESULTS: In this series of 85 cases, the satisfaction
      index was very high (66/85 patients, very satisfactory result), higher than the
      classical values obtained after other treatments of face wrinkles and defects
      (apart from botulinum toxin effects). The complication rate was very low, with
      only one reversible case in this series (infection of the tip on a multi-operated
      nose). The durability of results was dependent on the product: 4 months for
      botulinum toxin, 12 to 14 months after 2 injections for resorbable fillers.
      CONCLUSION: Medical rhinoplasty provides a large range of therapeutic solutions
      for minor corrections of nasal morphological or dynamic defects. The benefit/risk
      ratio for all aesthetic treatments must be high, what implies to reach the best
      result with the less complex, invasive and brutal protocol. This new approach for
      rhinoplasty fits in totally with actual patient expectations. The main
      inconveniences of this approach are the short durability of results and the cost
      of the procedure repetition.

PMID- 19408502
TI  - Endoscopic anatomy of the posterior tympanum.
AB  - OBJECTIVES: This study aims to describe anatomical variations in the posterior
      tympanum. Different configurations which influence surgical decisions in middle
      ear surgery are described. Surgical access to the sinus tympani remains a
      challenge for otologic surgeons. Usually, the retrotympanum is approached through
      the middle ear in the anterior-posterior direction during chronic ear surgery. An
      endoscopic approach is necessary to detail all reliefs of the middle ear and
      control the total removal in a cholesteatoma surgery. MATERIALS AND METHODS: Our
      study included 120 ears with otosclerosis that were operated on. We have
      performed an intra-operative endoscopic examination with different endoscopes
      from the Storz company (3.0 mm diameter 45 and 70 degrees). Its rigid endoscopes
      have been used to obtain a detailed inspection of the entire middle ear cavity.
      Three main anatomical configurations increase difficulty for the otologic
      surgeons. RESULTS: One hundred and twenty ears were included in this
      retrospective study. We described 44 shallow sinus tympani of type I (36.6%), and
      46 intermediary sinus tympani of type II which account for 38.4% of the ears. In
      these two groups, a disease such as cholesteatoma is quite easy to control. In 30
      ears we observed a deep sinus tympani of type III (25%). This type of sinus is a
      real difficulty for the surgeon, which means that a total exploration without an
      endoscope is not possible and entails intraoperative risks. Some anatomical
      variations were noted: indeed, six high jugular bulbs were described in the
      middle ear (5%). In 4 other ears (3.3%), there was a posterior extension which
      passes under the pyramidal eminence and the fallopian canal. CONCLUSION: For 8.3%
      of the ears, some important intraoperative risks are involved, which can cause
      damage to the facial nerve or the jugular bulb. Moreover a quarter of the ears
      have deep sinus tympani which can not be explored with a microscope. This makes
      the endoscope an essential complement to the microscope in otologic surgery.

PMID- 19408503
TI  - Possible role of biofilm in fulminant meningitis related to cochlear implantation
      of dysplastic inner ear.
AB  - Thanks to improvements in device design and surgical procedures, the number of
      potential candidates for cochlear implantation has been growing to include
      patients with inner ear malformations. Many precautions are taken pre-, peri- and
      postoperatively for these patients given the increased risk of surgical and
      medical complications, but with the rising bacterial resistance to antibiotics
      and the discovery of biofilm as a probable cause of chronic infections,
      postoperative morbidity remains higher than desired. OBJECTIVE: The purpose of
      this investigation is to describe histological findings on a temporal bone from a
      2-year-old infant with a cochlear implant and an inner ear deformity who died of
      bacterial meningitis. MATERIALS AND METHODS: The patient's temporal bone was
      studied under light microscopy, the cochlear implant studied with a scanning
      electron microscope, and later subjected to in situ hybridization to find
      bacterial DNA. RESULTS: The scanning electron microscopy image shows cellular
      formations on the surface of the implant, which later binds to the probe used for
      the in situ hybridization. CONCLUSION: There is evidence that bacterial DNA is
      present on the electrode array, which suggests existence of biofilm formation on
      the cochlear implant surface.

PMID- 19408504
TI  - Disability in patients with Meniere's disease following the use of two different
      treatment modalities: betahistine and intratympanic gentamicin.
AB  - OBJECTIVE: The objective of this study was to assess the level of residual
      disability and handicap in patients with Meniere's disease (MD) that were free of
      new vertigo spells 2 years after having been administered treatment with either
      oral medication or with intratympanic gentamcin. SETTING: University hospital.
      Tertiary medical center. MATERIAL AND METHOD: 40 patients with MD were included
      in this study, of which 20 were treated with oral medication (betahistine) and 20
      with intratympanic gentamicin; intratympanic gentamicin was for patients
      considered failures for the oral medication treatment. All of them are free of
      new vertigo in the 16-24 month period after beginning the treatment. They were
      matched by age and disease duration. Disability and handicap were assessed with
      conventional questionnaires at the time of inclusion and 2 years after beginning
      oral medication or ended the intratympanic gentamicin treatment. According to the
      treatment two groups were created: oral medication treatment and intratympanic
      gentamicin treatment. RESULTS: The amount of disability before treatment was
      higher in patients treated with intratympanic gentamicin than in those under oral
      medication; However, after treatment when no more vertigo spells takes place,
      this disability is significantly reduced and becomes similar for both groups of
      patients. In patients treated with oral medication the items reflecting the
      intensity of vertigo spell, the impact of vertigo in daily activities, the
      perception of quality of life and level of somatization do not show a significant
      reduction. CONCLUSION: The number or frequency of vertigo spells are very
      relevant for the process of disability and handicap of patients with MD when that
      is low or when oral medication is sufficient to eliminate vertigo spells. However
      when that number is high and the only possibility to arrest those vertigo spells
      is the use of intratympanic gentamicin, fear of vertigo must be considered as an
      associated problem for the patient.

PMID- 19408505
TI  - Hearing loss and vestibular function correlation in Meniere's disease patients.
AB  - OBJECTIVES: To analyse the correlation between vestibular dysfunction and hearing
      level of patients diagnosed with Meniere's disease. METHODS: Retrospective study
      on the correlation between hearing level and unilateral weakness in 100 Meniere's
      disease patients. In order assess the effect of disease severity in such
      correlation, the study group included 50 patients who subsequently were treated
      with oral medication and 50 who later received intratympanic gentamicin to
      control their symptoms. Audiogram and caloric tests were performed before
      beginning both of the treatments. Patients were classified according to the AAO
      HNS guidelines. Handicap was assessed with the Functional Level of the AAO-HNS
      and the Dizziness Handicap Inventory. RESULTS: No correlation was found between
      pure tone average and canal paresis neither when patients were analysed as a
      whole nor when correlation was controlled for the treatment installed afterwards.
      Nevertheless, when they were grouped by hearing loss AAO-HNS stages, we found a
      greater canal paresis in those with a higher hearing loss (groups 3 and 4).
      CONCLUSION: No correlation was found between hearing loss and canal paresis of
      patients diagnosed with Meniere's disease. However patients with a higher amount
      of hearing damage have a tendency to abnormal caloric results.

PMID- 19408506
TI  - [The emergency in the management of sudden hearing loss; still of present
      interest? A study of 109 cases of sudden deafness].
AB  - The emergency in the treatment of sudden hearing loss. A controversial dogma?
      OBJECTIVE: Does the delay in instigation of treatment in cases of sudden hearing
      loss affect the outcome? MATERIAL AND METHOD: 109 patients were included in this
      study. Sudden hearing loss is a much discussed subject in the literature. The
      authors agree on the concept of therapeutic emergency. This retrospective study
      aims to analyze the value of precocity in starting treatment on hearing
      improvement. RESULTS: The therapeutic time delay does not appear to be a
      significant factor and sheds doubt on the rule of therapeutic emergency.
      CONCLUSION: The authors remain nevertheless prudent on these conclusions. A
      larger number of cases should be studied. The question of a national versus
      placebo study is also laid.

PMID- 19408507
TI  - Static management of lagophthalmos following facial nerve paralysis using
      standardized weights.
AB  - OBJECTIVE: Peripheral facial nerve paralysis is accompanied by inability to
      properly close the eye and protect the cornea. The implantation of a standardized
      upper eyelid gold weight implant allows gravitational pull on the relaxed eye.
      METHODS: Custom-made gold implants were surgically implanted pre-tarsally in the
      upper eyelids of 37 patients with facial nerve paralysis. RESULTS: Excellent
      results were achieved in 36 patients. Repeated extrusion occurred in one case.
      CONCLUSION: This is a simple, reliable and especially reversible surgical
      procedure for the rehabilitation of the paralyzed eye.

PMID- 19408509
TI  - [Interest of the chest CT scanning in head and neck cancer].
AB  - INTRODUCTION: The overall survival rate for patients with head and neck squamous
      cell carcinoma remains disappointingly static despite improved locoregional
      control. This has been attributed to the development of distant metastases and
      second primary malignancies in these patients, a large proportion of which occur
      in the thorax. The goal of this study is to determine the incidence of newly
      thoracic malignancies diagnosed initially and during the follow-up in head and
      neck patients by chest computed tomography. METHODS: We retrospectively analysed
      the incidence of thoracic malignancies in 77 patients presented newly diagnosed
      cancer of the head and neck. RESULT: 15/77 patients were found to have thoracic
      malignancies. In 10/77 patients (14%) the diagnosis was made at the same time
      that the initial head and neck cancer In 5/77 patients, the thoracic malignancies
      were diagnosed during the follow-up. In 3 of the 5 cases, the pulmonary lesion
      was diagnosed in patients with local recurrent tumours. The primary site or the
      stage had an effect on the incidence of simultaneous thoracic malignancies.
      CONCLUSION: The presence of distant metastases and second primary malignancies
      has major implications in the management and prognosis of patients presenting
      with head and neck carcinoma. We recommend a CT scanning of the thorax in the
      staging of patients presenting with head and neck cancer but also in the follow
      up, particularly in patients with an advanced pharyngolaryngeal cancer.

PMID- 19408508
TI  - [Antro-choanal polyp in children. Our experience since 1997].
AB  - The antro-choanal polyp is a rather common pathology in children. OBJECTIVE: To
      discuss the diagnostic modalities, the risk factors, the differential diagnoses
      and treatment options. MATERIAL AND METHODS: This study was performed in an ENT
      department of a 3rd referal center Fifteen patients, 12 males and 3 females (8 to
      16 year old), were treated for an antro-choanal polyp (Killian's polyp) between
      1997 and 2007. RESULTS: All patients presented a nasal obstruction. Other signs
      of discovery were a rhinorrhea, a maxillary pain or a pharyngeal mass. Two
      patients presented a recurrence after a surgery in another center Atopy did not
      seem to be a risk factor. The imaging evaluation showed a tissular process
      developed in the maxillary sinus and extending through the maxillary ostium, or
      an accessory ostium, toward the nose. All patients were treated by intranasal
      endoscopic surgery. The middle meatal antrostomy was systematic, associated with
      a inferior antrostomy in 3 cases, with an anterior ethmoidectomy in one case and
      with a vestibular approach (Caldwell-Luc procedure) in 4 cases. Two patients
      presented a recurrence which necessited a new surgery. CONCLUSION: The antro
      choanal polyp must be suspected in front of nasal obstruction in children. The
      imaging evaluation eliminates the main differential diagnoses. The endo-nasal
      removal seems to be the best procedure.

PMID- 19408510
TI  - [Therapeutic management of glottic tumours: about a series of 41 cases of
      subtotal laryngectomy with cricohyoidoepiglottopexy (CHEP)].
AB  - OBJECTIVES: 1) To analyse the oncological and early functional results of partial
      supra-cricoid laryngectomy with crico-hyoido-pexy performed as a primary
      treatment modality on patients diagnosed with glottic squamous cell carcinoma
      involving the anterior commissure; 2) To propose a therapeutic management.
      PATIENTS AND METHODS: This is a retrospective study conducted over a period of 10
      years (1995-2005). Inclusion criteria included: 1) Squamous cell carcinoma of the
      vocal cords reaching the anterior commissure; 2) Absence of previous treatment
      for the glottic lesion; 3) Minimum follow-up period of 24 months. The functional
      results were evaluated according to duration of hospitalization, and the time
      elapsed before decanulation and realimentation. Statistical analysis was
      performed using the stat-view software. RESULTS: Forty-one patients underwent
      partial supra-cricoid laryngectomy. All patients had a tumour stage I or II. Mean
      follow-up was of 88 months. Tumour resection was complete in 95% of cases. The
      rate of lymph node involvement was 7.3%. Four patients (9.8%) developed local
      recurrence 13 months, on average, postoperatively. Three patients (7.3%)
      developed a metachronous lesion 14 months, on average, postoperatively. Three
      patients (7.3%) died during the follow-up period (2 cases related to the cancer).
      The specific survival and recurrence-free survival rates were 95% and 84.7%
      respectively. There was no statistically significant difference in survival rates
      between patients with stage I and stage II tumours. The mean duration of
      hospitalization was 24 days. The mean time intervals to decanulation and
      realimentation were 21 and 15 days respectively. CONCLUSION: Partial supra
      cricoid laryngectomy with crico-hyoido-pexy is one surgical option in laryngeal
      conservative surgery. This surgical procedure allows for adequate oncological
      control and good functional results as long as the indications are well respected
      and the surgical techniques are well mastered.

PMID- 19408512
TI  - [Results of alginate and hypertonic solution in wound healing of head and neck
      cancers].
AB  - INTRODUCTION: In head and neck cancers, complications such as pharyngostoma,
      orostoma, or fistula can present following surgery or surgery after irradiation.
      OBJECTIVE: To report the results of the association of two sea-derived products
      (Sinomarin and Algosteril) compared to normal saline for the management of
      healing. MATERIAL AND METHODS: This is retrospective study (1998-2000). Thirty
      patients were included in group 1 (Sinomarin-Algosteril) and 17 patients in group
      2 (normal saline). The average age was respectively 60 and 56.2. Patients in both
      groups presented with advanced head and neck carcinoma (T3-T4) and healing
      complications. RESULTS: The delay of healing was respectively of 33.53 and 72.94
      days. Results were statistically significant (Student T-test P < 0.05).
      CONCLUSION: Our results show the efficiency (p < 0.05) of the Sinomarin
      Algosteril association in head and neck cancer healing complications.

PMID- 19408511
TI  - [Surgical exploration of the sentinel lymph nodes in the papillary thyroid
      carcinoma].
AB  - OBJECTIVE: To study the technique of sentinel lymph node mapping in the papillary
      thyroid carcinoma and its evaluation in the search for cervical metastases.
      METHOD: Exploration of the sentinel lymph nodes of the papillary thyroid
      carcinoma by injection of methylene blue around the tumour among 25 patients
      during surgery. The nodes which stained blue and the other nodes removed by
      functional neck dissection were examined histologically after staining with
      hematoxylin-eosin-saffron (HES). We have evaluated the predictive value of the
      technique in mapping the cervical metastases in the sentinel lymph node. RESULTS:
      Among the 25 patients, 22 patients presented sentinel lymph nodes (blue-stained),
      that is to say a rate of identification of 88%. At histological examination, 19
      of the 22 patients had positive sentinel lymph nodes, of which 13 had also
      positive nodes not coloured with blue. The histological examination of patients
      without sentinel lymph node was negative. CONCLUSION: The technique of the
      sentinel lymph node has a strong positive predictive value in the search for
      cervical node metastases in the papillary thyroid carcinoma.

PMID- 19408513
TI  - [Congenital cholesteatoma of the mastoid].
AB  - The congenital cholesteatoma of the mastoid is rare and asymptomatic. CASE
      REPORT: We report a case of a young boy (5 year old) who presented mastoiditis,
      post auricular fistulisation and polyp of the external auditory canal. The
      mastoidectomy was performed and a cholesteatoma of the mastoid and the antrum was
      removed. No cholesteatoma was found in the tympanic cavity and the ossicular
      chain was normal. This surgery implies the complete removal of cholesteatoma and
      its matrix. One year after the patient showed no recurrency. CONCLUSION: The
      silent evolution of the congenital cholesteatoma explains the delay of its
      diagnosis and the risk of mastoiditis.

PMID- 19408514
TI  - Air rifle pellet injury to the middle ear, a very rare occurence.
AB  - INTRODUCTION: Air rifle pellet injuries are relatively common. These injuries
      often involve the brain, eyes chest or abdomen. It is rare for ENT surgeons to be
      involved in the care of these patients. CASE REPORT: We present the case of a 38
      year old man with a history of an air rifle pellet injury to the left ear.
      Presenting symptoms included bleeding per ear, otoalgia, hearing loss and
      tinnitus. Imaging and surgical exploration demonstrated a metallic pellet in the
      left petrous temporal bone, within the middle ear and a fracture of the anterior
      wall of the external auditory meatus with associated tiny metallic fragments. A
      further surgical exploration was required to remove a bony sequestrum of the
      anterior canal wall. CONCLUSION: The onset of pain and discharge a few months
      after the injury may imply the formation of a delayed sequestrum. The possibility
      of an implantation cholesteatoma should also be considered.

PMID- 19408515
TI  - [Tuberculous otomastoiditis: advantage of MRI in the treatment survey].
AB  - PURPOSE: Mycobacterium tuberculosis is a rare cause of otomastoiditis, accounting
      for less than a percent of chronic otitis media. The diagnosis is difficult and
      typically delayed because most physicians are unfamiliar with its presenting
      features and special laboratory requirements. Such delayed diagnosis leads to
      delayed treatment onset, and thus, increases complications frequency as
      irreversible hearing loss, facial palsy or meningo-encephalitis complications.
      Moreover non specific CT findings do not allow any accurate evaluation of inner
      ear lesions initially and under treatment. CASE REPORT: We described the first
      case of MRI of tuberculous mastoiditis and the evolution over a 2-years follow-up
      period. A patient with a clinical history of chronic otorrhea, resistant to
      conventional therapy, was referred to our department. CT and MRI permitted to
      describe the initial lesions and to appreciate the medical treatment efficiency
      (in order to perform surgery in case of failure or complications). Under medical
      treatment, MRI showed abscess volume decrease at three months while CT was still
      unchanged. Remineralization only was observed on CT at 12 months. The patient's
      healing was obtained after 15 months of antituberculous medication. CONCLUSION:
      MRI has the advantage over CT to demonstrate directly abscess collections that
      superimposed to areas of bone destructions within the temporal bone. Initially,
      MRI allows an accurate evaluation of abscess collections and possible meningo
      encephalitis complications. Moreover, MRI precises earlier than CT the
      improvement of lesions and the efficacy of medical treatment, and thus,
      permitting us to postpone surgery where it is unnecessary.

PMID- 19408516
TI  - Endoscopic endonasal surgery complication: new methods of intracavernous internal
      carotid artery injury treatment.
AB  - OBJECTIVES: To present new interventional neuroradiology methods of management of
      an ICA injury during functional endoscopic sinus surgery (FESS). CASE: The
      authors report the case of a patient who presented an ICA injury during a FESS
      and who could undergo an embolization. This embolization stopped the epistaxis
      and saved the patient from a lethal issue without any aftereffect. DISCUSSION:
      After a review of the literature the authors describe the circumstances of
      occurrence, the urgent management and the modern treatment of an ICA injury.
      Along with the progress in neuroradiology, the embolization represents a top
      grade treatment of this complication. Embolization with stent keeps permeable the
      ICA axis which represents a major progress in the management. CONCLUSION: The
      success of the management of an ICA injury relies on the close collaboration
      between anesthesist, otorhinolaryngologist surgeon and interventional
      neuroradiologist. Since 2004, modern techniques of interventional neuroradiology
      using new stents allow to keep permeable the ICA axis.

PMID- 19408517
TI  - [Decompression surgery for Bell's palsy: an evidence-based approach].
AB  - Bell's palsy is considered a benign pathology. However it can result in
      considerable long-term disability. Despite the development towards the better
      understanding of its physiopathology, treatment is still controversial,
      especially the indication of decompression surgery. Current practices are not
      standardised. Early medical therapy associating steroid drugs and antiviral
      agents after the onset of paralysis has become the gold standard. There is no
      evidence in favour of decompression surgery.

PMID- 19408518
TI  - Relevance of Choukroun's Platelet-Rich Fibrin (PRF) and SMAS flap in primary
      reconstruction after superficial or subtotal parotidectomy in patients with focal
      pleiomorphic adenoma: a new technique.
AB  - AIM OF THE STUDY: Parotidectomy leaves a retromandibular hollow area in
      proportion with the amount of gland resected. Many surgeons perform primary
      reconstruction after superficial or subtotal parotidectomy in patients with exo
      facial pleiomorphic focal adenoma. Many techniques have been proposed. We present
      a new technique of filling of the parotidectomy chamber by a second generation
      leucocyte and platelet concentrate, Platelet-Rich Fibrin (PRF, Choukroun's
      method). PATIENTS AND METHODS: 10 patients were included in this preliminary
      study. Subtotal parotidectomy was performed through classic procedure or lifting
      procedure. The macroscopic security margin of resection usually allowed
      performance of a SMAS flap. PRF was prepared following the original Choukroun's
      method. RESULTS AND DISCUSSION: PRF slow resorption after filling of the exeresis
      cavity, offers a key aesthetic interest. The fibrin matrix of this biomaterial
      has many angiogenic and healing properties. Synergetic action of the fibrin and
      the platelets cytokines within PRF may improve revascularization and
      postoperative resumption of facial nerve function. The membrane formed by the
      fibrin dense fibrillary network, as well as the SMAS flap, may help to prevent
      the Frey's syndrome. CONCLUSION: We propose the use of PRF as a filling, healing
      and interposition material after parotidectomy for benign parotid tumors.
      Preliminary results are very encouraging. Longer prospective evaluation of this
      technique is necessary.

PMID- 19408519
TI  - [Major orbital complications of acute maxillary sinusitis of dental aetiology].
AB  - OBJECTIVES: To demonstrate the importance of searching for a dental aetiology
      when confronted with an orbital cellulitis secondary to an acute unilateral
      maxillary sinusitis and to diagnose and treat as soon as possible in order to
      avoid visual sequelae. CASE REPORT: Two cases are presented. The first case of a
      35 year-old man who was diagnosed and treated late, for an orbital abscess
      secondary to a sinusitis of dental origin. The patient presented with visual
      signs such as diplopia and impaired occulomotoricity. The clinical diagnosis was
      concluded by an emergency sinus CT scan. Treatment consisted of an urgent
      surgical drainage associated to broad spectrum antibiotics with a high spectrum
      against Gram +cocci and anaerobes. Dispite this treatment regimen and two
      subsequent surgeries, the evolution was pejorative ending in a unilateral
      blindness. The second case is of a 45 year-old immunodeficient woman, presenting
      with the same pathology but without visual signs and whose evolution was
      satisfactory after adapted surgical and medical treatments. DISSCUSSION: The
      presence of visual and ocular signs warn on the gravity of the infection and
      indicate the need for urgent surgery. Sinus CT scan is essential to highlight the
      association between the orbit and the causal dental infection. For that, it must
      include the alveolar processes of the maxilla to show the dental lesion which is
      usually missed clinically. Functional endoscopic sinus surgery achieves two goals
      here; one diagnostic by the direct exploration of the nasal sinus cavities and
      the other therapeutic by the possible drainage all the paranasal sinuses.

PMID- 19408520
TI  - [Aneurysmal bone cyst of the ethmoid: paralateronasal or endoscopic surgery? Case
      report].
AB  - AIM: To report a typical case operated on under endonasal endoscopic surgery.
      CASE REPORT: A 20 year old girl came to the clinic with a left eye exophtalmus.
      Nasal endoscopy revealed a tumour developped into the left nasal fossa. Imaging
      allowed to suspect an ethmoidal aneurysmal cyst. CT showed a large tumour
      involving the left ethmoid, extending into the frontal and maxillary sinuses,
      with a fluid level in the middle of the tumour. MRI eliminated intracranial
      extension, showed a cystic component in the middle of the tumour and the presence
      of hemosiderin signals on T2. Complete resection of the tumour was performed
      under endoscopic endonasal surgery thanks to a cleavage plane between tumour
      periorbit and dura. Follow-up was simple with no recurrence at 2 years.
      CONCLUSION: Despite its rarity, this tumour needs to be known by ENT surgeons,
      and our surgical experience demonstrates that it can be resected endoscopically.

PMID- 19408521
TI  - [Case report on a nasal glioma: review of the literature].
AB  - A nasal glioma was discovered during routine examination of the nasal cavity
      patency of a newborn. An excision of the lesion was done by an intranasal
      approach under general anaesthesia. The intranasal endoscopic approach is
      strongly recommended for the removal of intranasal gliomas. Angled (30 or 70
      degrees) endoscopy allows visualisation of the cribriform plate which helps to
      rule out an intracranial extension.

PMID- 19408522
TI  - Frontal sinus osteoma complicated with intracranial inflammatory polyp: a case
      report and review of the literature.
AB  - BACKGROUND: Osteomas of the paranasal sinuses rarely cause intracranial
      manifestations. A neurological symptom may be the first sign of a previously
      unrecognized osteoma. CASE DESCRIPTION: A 28-year-old male was referred with one
      episode of witnessed tonic-clonic seizure and loss of consciousness. Radiologic
      examination revealed a calcific mass in the frontal sinus and a cystic structure
      was detected in the posterior component of the lesion. The patient underwent a
      combined nasal endoscopic approach and a bilateral frontal osteoplastic
      craniotomy. The ossifying tumoral tissue and the polypoid soft tissue mass were
      removed. The histo-pathologic diagnosis of the hard, bony tumor was consistent
      with an osteoma and the polypoid soft tissue was an inflammatory polyp.
      CONCLUSION: This case report illustrates a rare and life threatening complication
      of a frontal sinus osteoma with an intracranial extension of an inflammatory
      polyp.

PMID- 19408523
TI  - [Solitary myofibroma of the mandible: a case report].
AB  - OBJECTIVES: Infantile myofibromatosis (IMF) are integrated in the group of
      fibromatosis juvenile-type which are benign mesenchymal lesions, characterized
      morphologically by a proliferation of fibroblasts and myofibroblastes, with
      perivascular pattern. Through a case of solitary myofibroma of the mandible, we
      will emphasize anatomo-clinical features and differential diagnosis. MATERIALS
      AND METHODS: We report a case illustrating solitary myofibroma of the mandible in
      18 month old infant. RESULTS: The histological diagnosis was done on the
      identification of two separate components, a fascicular myofibroblastic pattern
      at the periphery with a hemangiopericytoma like pattern in the centre. Both
      components positive for alpha-smooth muscle actin and vimentin. DISCUSSION:
      Solitary IMF is characterised by a single lesion arising from cutaneous, bony or
      soft tissues. Morphological and immunohistochemical examination allow the
      diagnosis of the typical form. The differential diagnosis includes other benign
      spindle cells tumours. The prognosis is excellent with possibility to regress
      spontaneously.

PMID- 19408524
TI  - [Desmoplastic ameloblastoma in a 7 year old child].
AB  - Desmoplastic ameloblastoma is a benign, locally aggressive neoplasm of
      proliferating odontogenic epithelial origin. It is seen among old patients from
      17 to 72 years with an average age 42 years and without predilection of sex. We
      report the case of a 7 year old child, having presented since the 5 years age, a
      gingival tumefaction on the left higher incisivo-canin group which increased
      volume gradually. The stomatologic examination showed a gingival tumefaction
      covered with a healthy mucous membrane, ovoid form and measuring 3 cm on its
      horizontal axis. The tomodensitometry of the jawbone showed in front of the 21st
      and the 22nd tooth, the presence of an osseous lesion associating of the hearths
      of osteolysis and osteocondensation with rupture of cortical and invasion of the
      soft tissue. A curetting of the lesion was carried out and the anatomopathologic
      examination retained the diagnosis of desmoplastic ameloblastoma. The
      characteristic of our observation is the youth of the patient. In addition, the
      desmoplastic ameloblastoma is relatively rare, is characterized by an anatomical
      distribution, a radiological appearance and a morphological aspect differents
      from the traditional ameloblastoma. A radical surgical treatment is suggested for
      this tumour to avoid recurrency.

PMID- 19408525
TI  - Lingual granuloma of pregnancy.
AB  - Pyogenic granuloma gravidarum is a rare condition. There have been very few
      reports in the literature of these tumours affecting the tongue. We describe a
      case of pyogenic granuloma occurring on the tongue of a female who was 32 weeks
      pregnant. We present the clinical and histopathological features of this rare
      condition, discuss treatment options and review current literature.

PMID- 19408526
TI  - [Residual pocket depth after periodontal regenerative procedures. Clinical
      relevance and interpretation of meta-analyses data].
AB  - Meta-analyses allow to combine results systematically and to obtain more precise
      quantitative results on the efficacy of a therapy. For the clinician, the
      comparison of two therapy modalities is particularly of interest. Several meta
      analyses exist in the field of periodontal regenerative procedures. The problem
      is that the results are difficult to interpret for the clinician. It is only the
      clinical effect that can indicate the superiority of a certain treatment
      modality, e.g. remaining periodontal pockets. The aim of the present systematic
      review was the re-evaluation of studies of existing meta-analyses and to
      determine the probability of remaining periodontal pockets of more than 3
      respectively 5 mm after active therapy. The probability of remaining periodontal
      pockets over 3 respectively 5 mm was significantly higher after periodontal flap
      procedure without regenerative procedures, compared to guided tissue regeneration
      (GTR) or the use of enamel matrix derivatives. Moreover, the probability of
      remaining pockets over 3 mm was with GTR on average 57% and with the use of
      enamel maxtrix derivatives 74%. Using the cut-off value of 5 mm this probability
      was reduced to 8 and 17%, respectively. A new clinical attachment that was less
      than 50% of the original level was to be expected in 29% (GTR) and 15% using
      enamel matrix derivatives. This statistical interpretation permits not only the
      clinician, but also the patient to compare the efficacy of the different
      treatment modalities using the probability of primary clinical effect outcomes.

PMID- 19408527
TI  - [Cervicofacial actinomycosis: two case reports].
AB  - Infectious diseases transmitted by actinomycosis species cause severe destructive
      lesions. This rare and specific infection is mainly found in the orofacial
      regions. Causes of any hard tissue swelling in the jaw have, thus, to be assessed
      carefully. When actinomycosis is identified, a surgical intervention with
      curettement, draining and long-term antibiosis is required. The aim of the
      current article is to describe two clinical cases and to show the necessity of
      both, microbiological and histological laboratory diagnostics, to hedge the
      clinic diagnosis.

PMID- 19408528
TI  - [Treatment of localized gingival erythema].
AB  - Forms of a localized erythema can be observed occasionally as an expression of
      inflamed gingiva. It is characterized by a localized sharply demarcated and
      painless swelling of the gingiva with considerable redness. The differential
      diagnosis is not unequivocal and appropriate diagnosis and therapy are a
      challenge. In the present case presentation we report on three cases, which
      showed good disease remission after simple antiseptic prophylactic measures.
      Based on the available literature possible etiologic factors are reviewed and a
      pragmatic treatment strategy is discussed.

PMID- 19408529
TI  - [Follow-up after mammary carcinoma needs to be longer. Comment to the NHG
      standard 'diagnosis of mammary carcinoma'].

PMID- 19408530
TI  - [NHG-standard 'Diagnosis of mammary carcinoma'. Some differences with the
      multidisciplinary guideline].

PMID- 19408531
TI  - [Predicting asthma by means of wheezing at a young age is not possible].

PMID- 19408532
TI  - [Serious, symptomatic carotid stenosis. Preference for percutaneous angioplasty].

PMID- 19408533
TI  - [Serious, symptomatic carotid stenosis. Preferable not percutaneous angioplasty].

PMID- 19408534
TI  - [Organ donation: altruism, cooperation or both?].

PMID- 19408535
TI  - [Program for good samaritan kidney donation in Erasmus MC, 2000-September 2008].

PMID- 19408536
TI  - [The patient chooses for feasibility and effectiveness].

PMID- 19408537
TI  - [Septic arthritis after injection therapy in the shoulder].

PMID- 19408540
TI  - [Traffic accident at the end of pregnancy. Think of traumatic uterine rupture].

PMID- 19408538
TI  - [Humoral immunity and kidney transplantation. Possibilities and desensitizing
      treatment].

PMID- 19408541
TI  - [Active donor treatment needed for more organ transplantations].

PMID- 19408542
TI  - [Diagnostic image 412. A boy with skin pathology. Bite wounds, brought on by a
      child].

PMID- 19408552
TI  - [Sibling and family relationships].

PMID- 19408551
TI  - [Sibling bonds and care. Supporting the brothers and sisters].

PMID- 19408553
TI  - [Twins and cultures].

PMID- 19408554
TI  - [Care for siblings in the pediatric intensive care service].

PMID- 19408555
TI  - [A protocol for receiving brothers and sisters in neonatal intensive care].

PMID- 19408556
TI  - [The relationship between brothers and sisters in family placement situations].

PMID- 19408557
TI  - [A self help group for brothers and sisters of handicapped or sick children].

PMID- 19408558
TI  - [Caring for fathers by nurses during the birth of a first child].

PMID- 19408559
TI  - [3/12. Laryngeal dyspnea in children].

PMID- 19408560
TI  - [3/6. The pre-implantation diagnosis and the "drug baby"].

PMID- 19408561
TI  - Readers' perspective...Who is the most responsible for real-time transactions,
      particularly real-time claims adjudication?

PMID- 19408562
TI  - Digging into the economic stimulus law.

PMID- 19408563
TI  - What the stimulus package will, and won't, do.

PMID- 19408564
TI  - The team approach to I.T. building.

PMID- 19408565
TI  - The 2009 Nursing I.T. Innovation Awards.

PMID- 19408566
TI  - Rolling out the red carpet.

PMID- 19408567
TI  - How green was my hospital.

PMID- 19408568
TI  - Health care leaders plan to move toward innovative information technology.

PMID- 19408569
TI  - Keeping HIEs safe.

PMID- 19408570
TI  - Bedside manner and hardware choices.

PMID- 19408572
TI  - An EHR is not always a perfect fit.

PMID- 19408571
TI  - Cutting down on temporary staff.

PMID- 19408573
TI  - Drilling down.

PMID- 19408574
TI  - Development of pluronic micelle-encapsulated doxorubicin and formaldehyde
      releasing prodrugs for localized anticancer chemotherapy.
AB  - The chemotherapeutic agent doxorubicin forms drug-DNA adducts that are enhanced
      by formaldehyde-releasing prodrugs such as AN-9. One of the major limitations of
      doxorubicin is dose-limiting cardiotoxicity; therefore, the use of a targeting
      strategy that enables drug delivery and release at tumor sites is of great
      interest. The major aim of this study was to use the Pluronic-ultrasound delivery
      system to encapsulate doxorubicin and formaldehyde-releasing prodrugs within
      Pluronic micelles, and then use ultrasound to trigger controlled drug release
      from micelles. Pluronic micelles themselves were not stable upon dilution and
      required the use of a stabilizing agent DSPE-PEG2000 to form stable "mixed
      micelles." Following the separation of free doxorubicin, approximately 60% of
      doxorubicin remained encapsulated within mixed micelles with a retention half
      life of approximately 12 h. The formaldehyde-releasing prodrugs, however, were
      not retained within mixed micelles, but could potentially be administered
      separately to doxorubicin-loaded micelles to achieve tumor-localized formation of
      doxorubicin-DNA adducts. The use of low-frequency, high-power ultrasound (20 kHz,
      100 W/cm2) released 7-10% of doxorubicin from mixed micelles. Collectively, these
      results indicate that the Pluronic-ultrasound system could be used to deliver and
      release doxorubicin with the potential of forming cytotoxic DNA adducts at tumor
      sites with coadministrated formaldehyde-releasing prodrugs.

PMID- 19408575
TI  - Suppression of prometastatic phenotype of highly metastatic androgen-independent
      rat prostate cancer MLL cell line by PI3K inhibitor LY294002.
AB  - Upregulation of the PI3K pathway has often been reported in androgen-independent
      prostate cancer and is implicated in cancer cell survival and proliferation in
      the absence of androgen. Inhibition of PI3K by LY294002 suppressed cell invasion
      and motility of the highly metastatic androgen-independent Dunning rat prostate
      cancer MLL cell line with similar IC50 values and inhibition profile. Moreover,
      LY294002 attenuated expression of urokinase plasminogen activator (uPA) without
      any significant effect on that of matrix metalloproteinase 2. These results
      indicated that the role of PI3K in MLL cell invasion is by regulating cell
      motility and uPA expression.

PMID- 19408576
TI  - Effects of cardiotoxin III on NF-kappaB function, proliferation, and apoptosis in
      human breast MCF-7 cancer cells.
AB  - Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues
      isolated from Naja naja atra venom, has been reported to have anticancer
      activity. CTX III-induced apoptosis in human breast MCF-7 cancer cells was
      confirmed by sub-G1 formation, phosphatidylserine (PS) externalization, and poly
      (ADP-ribose) polymerase (PARP) cleavage with an IC50 of 2 microg/ml at 48 h.
      Effects of CTX III on proliferation and apoptosis correlated with upregulation of
      Bax, and downregulation of Bcl-XL, Bcl-2, and XIAP, with no appreciable
      alteration on the protein levels of Bid, Bim, and survivin. CTX III treatment
      also caused release of mitochondrial cytochrome c to the cytosol, which led to
      subsequent activation of capase-9. Moreover, CTX III inhibited the nuclear factor
      kappaB (NF-kappaB) activation through inhibition of IkappaB kinase (IkappaK)
      activity. Overall, our results indicate that CTX III downregulates NF-kappaB in
      MCF-7 cells, leading to the suppression of proliferation and induction of
      apoptosis. These findings suggest the molecular basis for CTX III-induced
      apoptotic death of MCF-7 cells.

PMID- 19408577
TI  - Genetic polymorphism in UDP-glucuronosyltransferase 2B7 and colorectal cancer
      risk.
AB  - Colorectal cancer (CRC) is one of the most common malignancies in the Western
      world. CRC is strongly associated with lifestyle factors. Susceptibility to CRC
      may be partly due to deficient detoxification capacity in the gastrointestinal
      tract. Genetic polymorphisms in detoxification enzymes result in variations in
      detoxification activities, which might influence the levels of carcinogens in the
      gastrointestinal tract, influencing the risk for CRC. To determine whether a
      genetic polymorphism in the detoxification enzyme UDP-glucuronosyltransferase 2B7
      (UGT2B7) predisposes to CRC, 411 Caucasian patients with sporadic CRC and 600
      Caucasian controls recruited from the same geographic area were genotyped for the
      functional UGT2B7 H268Y polymorphism. DNA was isolated and tested by a dual-color
      real-time polymerase chain reaction assay. Overall, no differences in genotype
      distributions between patients with CRC and controls were observed. When analyzed
      with respect to tumor location, a shift from the UGT2B7*I *2 into the UGT2B7*2*2
      genotype was seen in patients with proximal CRC (OR 1.80, 95% CI 1.11-2.89). In
      the male patient subpopulation an even stronger association was observed (*1*1 +
      *1*2 vs. *2*2: OR 2.17, 95% CI 1.11-4.04; *1*2 vs. *2*2: OR 2.19, 95% CI 1.10
      4.37). No associations with respect to tumor stage were seen. In conclusion, the
      frequency of the UGT2B7*2*2 genotype is higher in CRC patients with proximal
      location of the tumor, especially in males, which suggests that this genotype is
      associated with an increased risk for proximal CRC.

PMID- 19408579
TI  - Morphological evaluation of the human pyramidal tract: tapering of axons.
AB  - It is generally accepted that nerve fiber conduction velocity is directly
      proportional to the fiber diameter under the condition, based on a supposition,
      that the transverse area of axons is normally maintained constant. Using an ideal
      preparation method for the purpose of axonal discrimination, we examined 43 human
      spinal cords after making transverse sections at the cervical, thoracic, lumbar
      and sacral levels and found a tapering of the axons in the lateral pyramidal
      tract, as the cross-sectional area of the pyramidal axons showed a definite
      decrease from the cervical to the sacral levels. Our results contradict the
      supposition that the transverse area of axons is normally maintained constant,
      which has for a long time been believed to be true without any evidence for it.

PMID- 19408578
TI  - Relationship between FDG uptake and expressions of glucose transporter type 1,
      type 3, and hexokinase-II in Reed-Sternberg cells of Hodgkin lymphoma.
AB  - Reed-Sternberg (R-S) cells are the main tumor cells of Hodgkin lymphoma (HL). HL
      has been reported to demonstrate a high level of [18F]2-fluoro-2-deoxy-D-glucose
      (FDG) uptake, but the determinant of FDG uptake for HL has not been well
      elucidated. Thus, we investigated the relationship of FDG uptake and the
      expressions of glucose transporter type 1 (Glut-1), glucose transporter type 3
      (Glut-3), and hexokinase II (HK-II) in R-S cells of HL. There were 25 tissue
      proven HL patients from January 2003 to July 2007 in our hospital. Of the 25 HL
      patients, 4 cases obtained by surgical excision were included in the present
      study. The immunostaining for Glut-1, Glut-3, and HK-II was conducted in the
      excised masses. The maximum standardized uptake values (maxSUVs) were compared to
      the expressions of Glut-1, Glut-3, and HK-II. Three HL patients (mixed
      cellularity = 2 and nodular sclerosis = 1) demonstrated moderate-strong
      expressions of Glut-1 in almost all R-S cells, and of these three HL patients,
      two underwent FDG-PET, which revealed a high level of maxSUVs (7.7, 6.5) in the
      corresponding HL lesions. One HL patient (lymphocyte depletion) showed weak Glut
      1 expressions in only 10% of R-S cells, but no FDG-PET study was available. The
      expressions of Glut-3 and HK-II were various in all four HL patients, and no
      specific correlations with FDG uptake were found. In conclusion, high expressions
      of Glut-1 in R-S cells may play a crucial role for the high FDG uptake in Hodgkin
      lymphoma.

PMID- 19408581
TI  - Light and scanning electron microscopic study on the tongue and lingual papillae
      of the Japanese badgers, Meles meles anakuma.
AB  - We observed the three-dimensional structures of the external surface and
      connective tissue cores (CTCs), after exfoliation of the epithelium of the
      lingual papillae (filiform, fungiform and foliate papillae) of the Japanese
      badgers (Meles meles anakuma) using scanning electron microscopy and conventional
      light microscopy. Macroscopically, the tongue was elongated anterior-posteriorly
      and the apex rounded. Numerous filiform papillae and fungiform papillae were
      distributed all over the tongue except at the root. Seven vallate papillae were
      observed that had circumferential furrows and were arranged in V-shape. Numerous
      taste buds were observable in the furrows. Instead of foliate papillae, a lateral
      organ lacking taste buds was present on the lateral edge of the posterior tongue.
      Behind the vallate papillae, dome-like lingual tonsils that had globular tonsils
      were densely distributed in U-shaped arrangement. Rather long conical papillae
      were distributed around the vallate papillae. At the posterior end of the root of
      the tongue, lingual papillae were very much attenuated and only fold-like
      structure was seen. CTCs of filiform papillae had a main rod-like slender core
      and ovally arranged short accessory cores distributed around the main core. CTCs
      of fungiform papillae exhibited a columnar like appearance. The lingual papillae
      of Japanese badger's tongue fundamentally had morphological similarity with
      carnivore species, included the Pinnipedia.

PMID- 19408580
TI  - Morphometric and functional correlation of human neuronal somata: pyramidal
      motor, special sensory and general sensory systems.
AB  - Using an ideal tissue preparation method, we found a definite correlation between
      various human neuronal somata from the view point of accurate morphometry and
      functional evaluations. We believe this study may be of value, or even
      indispensable in the correct understanding of neurological symptomatology and
      phenomenology.

PMID- 19408583
TI  - Morphological study of the connective tissue papillae and the capillary loops on
      the lingual dorsum in the type 2 diabetes mellitus model rats.
AB  - We performed a morphological study in type 2 diabetes mellitus (DM) model rats by
      focusing on the connective tissue papillae (CTPe) and capillary loops (CLs) of
      filiform papillae in the lingual dorsum in the type 2 DM model rats (GK rats).
      The normal group comprised nine 8-week-old male Wistar rats. The DM group
      comprised nine 8-week-old male GK rats. Image analysis of light microscopic
      specimens in CTPe was performed (height and cross-sectional area). Image analysis
      of scanning electron microscopic specimens (acrylic plastic injection method) in
      CLs was performed (number, thickness, height, interval between the tops of the
      two CLs, and crossing ratio between ascending and descending crura (CRC)). We
      compared these values between both groups (Student's t test). The former analysis
      revealed that the height and cross-sectional area of CTPe were smaller in the DM
      group than in the normal group. The latter analysis revealed that the thickness,
      height, and CRC of the CLs were smaller in the DM group than in the normal group.
      However, no significant differences were detected in the number and interval of
      CLs between both groups. Therefore, we concluded that DM caused regressive change
      in CTPe and CLs.

PMID- 19408582
TI  - Morphological changes in the lingual papillae and their connective tissue cores
      on the 7,12-dimethylbenz[alpha]anthracene (DMBA) stimulated rat experimental
      model.
AB  - The aim of the study was to analyze morphological changes of the epithelial
      surface and underlying connective tissue cores (CTCs) of the lingual mucosa in
      the rat using a DMBA induced pre-cancerous experimental model.
      Lightmicroscopically, initially DMBA treated sections exhibited infiltration of
      chronic inflammatory cells. At 16 weeks, aldehyde-fuchsin (AF) positive elastic
      fibers decreased and were scanty in the juxtaepithelium. On the other hand,
      rather densely packed thick bundles of AF positive fibers were observable in the
      deep layers of lamina propria. Carcinomas were not found at any stage, however,
      epithelial dysplasia was observed at 24 weeks post-treatment with DMBA. Scanning
      electron microscopy revealed an irregular arrangement of filiform papillae 4-12
      weeks following DMBA stimulation. Patchy degenerated areas were observed
      especially at 16-24 weeks post-treatment and filiform papillae were totally
      attenuated on the central part of the degenerated areas. After removal of the
      epithelium, attenuated CTCs were observed from 4-8 weeks. Morphology of CTCs
      seemed to be gradually remodeled and severely altered in the later stage. The
      CTCs were however attenuated and exhibited a patchy distribution. The animal
      experimental model in this study revealed degenerative morphological changes of
      CTCs of the lingual papillae in the precancerous stage induced by DMBA.

PMID- 19408584
TI  - Effects of amifostine administration prior to irradiation to the submandibular
      gland in mice: autoradiographic study using 3H-leucine.
AB  - We histochemically investigated the radioprotection of organelle in acinus on the
      submandibular gland using amifostine. Mice were divided into those without
      amifostine administration or irradiation (group A), with amifostine
      administration and without irradiation (group B), without amifostine and with 5
      Gy of irradiation (group C), and with amifostine and 5 Gy of irradiation (group
      D). In groups B and D were given 100 mg/kg of amifostine at 30 minutes prior to
      irradiation to the area equivalent to the submandibular gland. HE staining
      revealed that group D showed atrophy of the acinar cells, though the change was
      milder than that seen in group C. In AZAN-Mallory staining, fibrogenesis were
      found more often in group C as compared to the other groups. In Light Microscopic
      Autoradiography findings, the ratio of reduced silver particles in the acinar
      cells was lower in group C than in the other groups at 30 minutes after RI
      administration. Microstructure findings showed the findings were very similar to
      those of group A. In Electron microscopic Autoradiography, the ratio among the
      secretory granules was lower in group C at 120 minutes after RI administration.
      Our results indicate that amifostine can alleviate xerostomia caused by late
      effect from radiation.

PMID- 19408585
TI  - American Indian predental students need help.

PMID- 19408586
TI  - The top ten myths about CO2 lasers in dentistry.

PMID- 19408587
TI  - Recreating Mother Nature with direct resin restorations.

PMID- 19408588
TI  - Utilizing digital imaging to enhance the team approach to implant treatment.

PMID- 19408589
TI  - Comprehensive dentistry using chairside CAD/CAM technology: a case report.

PMID- 19408590
TI  - Alginate substitutes: rationale for their.

PMID- 19408591
TI  - Photodisinfection: the future of periodontal therapy.

PMID- 19408593
TI  - Magnification in dentistry: how ergonomic features impact your health.

PMID- 19408592
TI  - Ahead of the curve: future directions in endodontics.

PMID- 19408594
TI  - The hygiene assistant: is this position right for your practice?

PMID- 19408595
TI  - The dental GPS: your guide to happiness and satisfaction.

PMID- 19408596
TI  - Can you grow in this economy?

PMID- 19408597
TI  - Birth intervals and infant mortality in La Cabrera (Spain).
AB  - Family reconstitution has provided knowledge about the reproductive performance
      of mates from La Cabrera (northwest Spain). The analysis of 2293 reconstituted
      families (7872 births corresponding to parities 2 to 10) was restricted to the
      period 1880 to 1929. The proportion of infant deaths (younger than 1 year) was
      calculated regarding the preceding birth interval and the death or survival of
      the previous sibling. Considering as dependent variables the neo and the
      postneonatal mortality, a logistic regression was obtained. From the present
      analysis it is concluded that in La Cabrera 45% of couples have the most
      effective reproduction with birth intervals of 24 to 36 months. Risk factors
      regarding neonatals were found to be intervals shorter than 17 months, the death
      of the preceding sibling and male sexuality. Neither maternal age nor the
      accumulated number of previous sibling deaths were significant risk factors.

PMID- 19408598
TI  - Growth and nutritional status of pre-school children in India: rural-urban and
      gender differences.
AB  - This cross-sectional study of growth and nutritional status makes an attempt to
      find the gender and rural-urban differences among Indian preschool children. This
      study is based on the data of weight and height of children aged 0-35 months
      taken from 26 States (total 26,369 children; 13784 boys and 12585 girls). The
      children are found to be lighter and shorter compared to International standards
      irrespective of age and sex. Boys are heavier and taller than girls. Urban
      preschool children are heavier and taller compared to rural counterparts. In the
      urban area, higher percentages of girls are affected by underweight (37.1%) and
      stunting (35.0%) than boys. In rural areas, the prevalence of underweight is also
      higher among girls (47.9%) compared to boys (45.7%), which is found to be much
      significant (p < 0.01). There is a significant rural-urban as well as gender
      difference in growth and nutritional status of Indian preschool children.

PMID- 19408599
TI  - Age at menarche in schoolgirls from Tanzania in light of socioeconomic and
      sociodemographic conditioning.
AB  - The goal of this study is to determine the age at menarche of girls from Tanzania
      examined in 2005 considering their families' social and material status. For the
      purpose of the analysis of the age at menarche, N = 71 girls were qualified (N =
      8 from Dares Salaam and N = 63 from Mafinga) out of N = 98 who took part in the
      anthropological study. The calendar age of the girls who qualified for the
      determination of the age at menarche ranged from 12.9 to 22.7 years of age (X =
      15.9 +/- 1.9). The age at menarche revealed using the recall method was 14.3 +/-
      1.1 years. The menarche of the girls included in the study with a parent (mother
      or father) residing in town was found to be earlier (14.1 and 14.0 respectively).
      When neither parent completed schooling or had only primary education, the age at
      the daughter's menarche was on average 15.0 years. The girls whose fathers
      completed secondary school had their first menstruation at 14.8 years, while the
      daughters of mothers who finished secondary school--at 14.5. The lowest age at
      menarche was found in the group of girls whose parents obtained higher education
      (13.4 years in the case of the father and 13.3 in the case of the mother). A
      higher age at menarche was typical of the group of girls from families in which
      the number of children in the household was > or = 6 (15.2). In the two-way ANOVA
      equation, the lowest age at menarche was found in the girls whose families lived
      in town and had higher education, while the highest--where the family lived in
      the countryside and did not finish school or had primary school only. In the two
      way ANOVA equation (education*self-estimation of the family's material
      situation), the lowest age at menarche (13.2) was found in the group where the
      father had higher education and the material situation was assessed as very good
      or rather good. My own studies are representative for similar African
      environments. The results obtained allow for comparison with research findings
      for highly developed countries, yet it is difficult to ascertain unanimously
      whether the causes for the age at menarche decreasing are the same. It seems that
      Africa with its environmental conditioning is governed by its own rules.

PMID- 19408600
TI  - Finger dermatoglyphic variations in Rengma Nagas of Nagaland India.
AB  - The Rengma Nagas are one of the major Mongoloid tribal populations in the North
      Eastern state of Nagaland in India. Population variation and sexual dimorphism in
      respect of finger dermatoglyphic characteristics in 207 adult individuals (104
      males and 103 females) are reported in this present context. Frequency
      distribution of finger pattern types in different digits (both left and right
      sides combined) showed that whorls were the most prevalent patterns among both
      males (52.19%) and females (55.69%), followed by loops (47.70% in males and
      42.81% in females). Significant sex differences in Dankmeijer Index (t = 1.47; p
      < 0.0001) and finger wise variations of total finger ridge count (TFRC) and
      absolute finger ridge count (AFRC) in both the sexes were recorded. However, in
      cases of the frequencies of finger dermatoglyphic pattern types, Pattern
      Intensity Index in fingers, TFRC and AFRC no significant sex differences were
      observed.

PMID- 19408601
TI  - A new tibial torsiometer applicable to clinical practice.
AB  - This study evaluated a new tibial torsiometer that is universally applicable to
      all limb sizes and requires no special training, jigs, or radiographic equipment.
      To compare the reliability of measurements obtained with the torsiometer, 160
      tibias were evaluated with both the torsiometer and computed tomography. Results
      for both methods were identical in 51 tibias, within 1 degrees in 66 tibias, and
      within 2 degrees in 43 tibias. The difference between the two methods was not
      significantly different. No significant differences were found among examiners.
      This device should prove to be useful for the quantification of tibial torsion.

PMID- 19408602
TI  - Treatment of tibial bone defect with rotational vascular periosteal graft in
      rabbits.
AB  - It is well known that the periosteum is capable of bone formation. In the present
      study, the value of the vascularized periosteal graft in healing the long-bone
      defect filled with the allogenous bone graft was studied. The aim of the study
      was to verify the efficiency of the rotational vascularized periosteal graft as a
      optional surgical method as well as to prove its advantages in comparison with
      the nonvascularized periosteal graft. The study was undertaken on 40 rabbits.
      Four rabbits served as allogenous bone graft donors, while the remaining 36 were
      divided into two equal groups. In the control group, the experimentally created
      bone defect on the junction of the tibial proximal and median thirds was filled
      with allogenous bone graft and then covered with avascular periosteal graft. In
      the experimental group, the allogenous bone graft filled defect was covered with
      the rotational vascular periosteal graft. Groups of 6 rabbits from each group
      were sacrificed after 2, 5 and 12 weeks following surgery. The results were
      evaluated with radiographical, histological and morphometric methods. The results
      obtained 2 and 5 weeks after surgery demonstrated better tibial bone defect
      healing in the experimental group. The defect was bridged in both analysed groups
      after 5 weeks and was completed after 12 weeks with no difference between the
      control and the experimental groups. The obtained results have confirmed the
      efficiency of the method using the rotational vascularized periosteal graft in
      the treatment of tibial bone defect in rabbits. The advantage of the vascularized
      periosteal graft as compared to the avascular one has been proved by better
      quality of bone healing in the early stage.

PMID- 19408603
TI  - Initial experience with external thoracic stabilization by the "figure of eight"
      osteosynthesis in polytraumatized patients with flail chest injury.
AB  - The aim of this study was to describe initial experience with external thoracic
      stabilization by the "figure of eight" osteosynthesis in polytraumatized patients
      with flail chest injury. From January 2002, fifteen patients underwent this
      surgical procedure at the University Hospital of Rijeka. Their mean age was 52 +/
      13.69 (range 18-65) and mean ISS was 29.8 (range: 20-41). Twelve patients were
      weaned from artificial respiration on same day when operated, two on the post
      operative day 1, and one on the post-operative day 2. Their stay within the
      intensive care unit following extubation was within the range of 1-12 days (mean
      3.93 +/- 2.99). The early external thoracic stabilization by the "figure of
      eight" osteosynthesis was followed by swift extubation of patient and direct
      normalization of respiratory parameters. This method contributed significantly to
      patient's shorter stay within the intensive care unit.

PMID- 19408605
TI  - Comparison between continuous ambulatory arterial blood pressure monitoring and
      standard blood pressure measurements among patients of younger and older age
      group.
AB  - The purpose of the study was to evaluate whether there is a difference between
      blood pressure measured in a physician's office and the average 24 hr continuous
      blood pressure monitored by hypertensive patients at home. If there is a
      difference between these two situations then is it possibly the result of a blood
      pressure response by the patient to the physician which is known as "white coat
      effect" or "white coat hypertension". We studied 80 hypertensive outpatients
      which were divided into two groups of 40 patients each--a younger patient group,
      with a mean age of 22.8 +/- 1.8 years, and an older patient group with a mean age
      of 50.3 +/- 5.7 years. They were selected because they had been diagnosed as
      essentially hypertension grade 1, according to 2007 ESH/ESC Guidelines, or the
      USA Joint National Committee Guidelines (JNC 7) (i.e., arterial blood pressure >
      140/90 mm Hg and < 160/100 mmHg) and 35 were not having any antihypertensive
      treatment. All participants in the study went through a two-week "wash-out"
      period without medication. At the beginning of the study blood pressure was
      measured using the Riva-Rocci-Korotkoff method (mercury sphygmomanometer) after 5
      minutes of rest and with the patient in the sitting position. The average of the
      two last measurements by sphygmomanometer was used in the analysis. The
      subsequent measurement was made by continuous ambulatory blood pressure
      monitoring (SpaceLabs 90207 device). Continuous ambulatory blood pressure
      monitoring revealed that 17 patients of the younger age group (42.5%) who were
      diagnosed hypertonic, according to mercury sphygmomanometeric measurement, were
      in fact normotonic. In the older age group only 7 (17.5%) of participants were
      normotonic during 24 hr blood pressure monitoring. The proportion of miss
      diagnosed normotonic younger patients was directly related to elevated clinic
      blood pressure, which could be referred to as office hypertension or isolated
      clinic hypertension (white coat hypertension). This was statistically significant
      (chi2 = 5.95; p = 0.015). Hypertension diagnosed in younger patients based only
      on occasional doctor's office mesurements, using a mercury sphygmomanometer,
      could be miss-interpreted and treated as the start of arterial hypertension. This
      could sometimes have unwanted results due to the side effects of precipitate
      antihypertensive medication as well as the unnecessary cost of testing, cost of
      treatment, prevalence of white-coat hypertension at baseline, and the varying
      incidence of new hypertension after the initial screening. The results indicate a
      potential savings of 3-14% in the cost of care for hypertension, and a 10-23%
      reduction in treatment days when ambulatory blood pressure monitoring is
      incorporated into the diagnostic process. Therefore CABPM should be used as a
      legitimate method in the diagnosing of "white coat hypertension", particularly in
      young patients. The identification of white coat hypertensive"' patients should
      be followed by a search for metabolic risk or organ damage using the latest
      guidelines, and medication should start after an organ damage or cardiovascular
      risk assesement.

PMID- 19408604
TI  - The epidemiology and diagnostic approach to acute pulmonary embolism in the
      university hospital.
AB  - The aim of this retrospective study was to evaluate the demographics and clinical
      characteristics of patients with pulmonary embolism treated in medical intensive
      care unit (ICU) at the University Hospital during a six-year period, and to
      assess the impact of several risk factors on patients' survival. The study
      included 165 patients, mean age 69.3 +/- 13.7 years, predominantly female
      (70.3%). Dominant symptom was dyspnea (97.0%), the most common sign tachypnea
      (69.6%). Pulmonary embolism was confirmed by high-probability
      ventilation/perfusion lung scan or multidetector computed tomography in 71.5% and
      was regarded as massive in 63 (38.2%), submassive in 23 (13.9%) and non massive
      in 79 patients (47.9%). Mean hospital stay was 5.7 +/- 4.4 days for ICU, and 14.8
      +/- 9.1 days, overall. The ICU mortality was 26.7% and in-hospital mortality
      30.9%. No statistical difference in mortality between male and female patients
      was observed (30.6% and 31.0%, respectively; p = 0.965), but prolonged
      immobilization (p = 0.002), recent operation (p = 0.034) or malignancy (p =
      0.009) were shown to influence the outcome. Although a number of risk factors for
      developing pulmonary embolism have been identified and heparin prophylaxis along
      with early mobilization proposed to reduce the incidence, pulmonary embolism
      remains an important clinical problem with high mortality rate. The diagnostics
      should not wait and the therapy should start as soon as possible.

PMID- 19408606
TI  - Treatment of hypertension by general practitioners and antihypertensive drugs
      expenditure in an urban environment.
AB  - Aim of our study was to determine the treatment habits of hypertension by general
      practitioners (GPs) as well as the monthly costs of prescribed antihypertensive
      drugs and their share in the total prescription drug expenditure approved by the
      Croatian Institute for Health Insurance (CIHI), the compulsory health insurance
      system. The study was performed in six GPs offices in Zagreb, serving 8,866
      patients, in December 2005. The monthly costs of antihypertensive drugs
      prescribed by the GPs was obtained by summarizing the prices of all
      antihypertensive drugs prescribed in one month and then comparing the sum with
      total monthly prescription drug expenditure approved by the CIHI. The type and
      dosage of prescribed antihypertensive drugs were also analyzed. Hypertension was
      diagnosed in 2,342 (26.4%) patients. The monthly costs of prescribed
      antihypertensive drugs accounted for 52.33% of the total amount approved for
      medications by the CIHI. 945 (40.0%) hypertensive patients were taking
      antihypertensive monotherapy. The most frequently prescribed drugs as monotherapy
      were ACE inhibitors (38.3%), calcium-channel blockers (26.7%), beta blockers
      (18.6%), and diuretics (10.3%). a antagonists (3.6%). Angiotensin receptor
      blockers (2.5%) were rarely prescribed. As combination therapy, ACE inhibitors
      and diuretics (30.4%) were most frequently used. More than 50% of the funds
      allocated to GPs for medications were spent for the treatment of only one
      disease. The most used antihypertensive drugs were ACE inhibitors.

PMID- 19408607
TI  - Tissue ischemia due to CO2 pressure during laparoscopic radical prostatectomy.
AB  - Laparoscopic radical prostatectomy is nowadays one of the most frequently
      performed urological surgical procedures. For insufflation in laparoscopic
      radical prostatectomy (LRP) CO2 is used, with the pressure in the operative
      region between 12 and 15 mm Hg. At the microcirculation level, the pressure is
      lower, which raises the possibility of ischemic tissue damage during the
      procedure. The activity of glutathione peroxidase (GSH-px), superoxide dismutase
      (SOD) and catalase (CAT) was measured at the beginning and immediately after the
      end of the surgery in 44 patients who underwent LRP and in 11 who underwent
      retropubic radical prostatectomy (RRP). Capillary endothelial damage was assessed
      by applying immunohistochemical and morphometric methods to tissue samples from
      the urinary bladder neck, which contains all layers of the bladder wall.
      Measurement of the enzyme activity showed no significant increase of GSH-px (p
      0.431), SOD (p-0.220) and CAT (p-0.434) levels. Neither immunohistochemical
      analysis of the bladder neck capillaries with i-nitric oxide synthase (i-NOS) nor
      morphometric analysis showed signs of endothelial ischemic damage.

PMID- 19408608
TI  - Acute phase proteins in psoriasis.
AB  - Psoriasis is a chronic, relapsing, inflammatory and hyperproliferative skin
      disorder. The levels of acute phase proteins are suggested to be elevated in
      those patients with acute disease. The expression of selected acute phase
      proteins as the parameters of humoral immunity has been analyzed in 70 patients
      with acute psoriasis and 40 healthy controls. The aim was to evaluate the
      inflammatory response in the exacerbation of psoriasis and to determine the
      correlation of these objective inflammatory parameters with clinical features of
      disease activity. Main demographic and epidemiologic features were, as well,
      analysed. The plasma levels of C-reactive protein (CRP) (chi2 = 23.61; p <
      0.005), and alpha1-acid glycoprotein (alpha1-AGP) (chi2 = 7.42; p < 0.01) were
      significantly increased in those patients with acute phase of the disease
      compared to healthy controls. Our results suggest that psoriasis is an
      inflammatory disease and therefore its worsening seemed to be linked to the
      increase in the inflammatory response. It seems that CRP and al-AGP levels could
      serve as important prognostic factors for the worsening of psoriasis.

PMID- 19408609
TI  - Endoscopic CO2 laser surgery for supraglottic cancer--ten years of experience.
AB  - We present our experience with primary CO2 laser surgery for planocellular
      supraglottic carcinoma. During a ten-year period, we performed 64 curative
      supraglottic laryngectomies. Twenty-nine patients presented with T1 and 35 with
      T2 carcinoma. There were 46 patients without regional and/or distant metastases
      (N0 neck), and 18 patients with N+ neck. Thirty-three (52%) patients were treated
      with surgery alone, and in 31 (48%) patients surgical procedure was combined with
      radiotherapy. Estimated overall 5-year survival for all patients was 89%. Local
      and regional tumor control as well as survival rate were comparable with the
      results of other therapeutic options, i.e. radiotherapy or open supraglottic
      laryngectomy. Functional results outline the advantages of endoscopic laser
      surgery for laryngeal carcinoma. Transoral endoscopic CO2 laser surgery is
      efficacious treatment for T1 and T2 supraglottic carcinoma, and can be combined
      with neck dissection and postoperative irradiation.

PMID- 19408610
TI  - HIV infection, as opposed to antiretroviral therapy, does not cause changes in
      the concentration levels of specific salivary electrolytes.
AB  - The concentration levels of salivary calcium, magnesium and zinc can vary in
      different localized oral, as well as systemic diseases and conditions. So far
      changes in the concentration levels of specific electrolytes in stimulated
      parotid saliva in HIV-positive/AIDS patients have been proven. The objective of
      this research was not only to study the concentration levels of calcium in non
      stimulated total saliva, but also the concentration levels of magnesium and zinc,
      which have not been studied so far, and the influence of antiretroviral therapy
      (HAART). This research was conducted on 60 healthy subjects with an average age
      of 40.4 years, and 60 HIV-positive patients with an average age of 43.7 years, 45
      of whom took HAART therapy. The concentration levels of calcium, magnesium and
      zinc in saliva were determined by means of an atomic absorption
      spectrophotometry. No significant differences in the levels of excreted saliva/5
      minutes (p = 0.116), the concentration levels of salivary calcium (p = 0.713),
      magnesium (p = 0.600), nor zinc (p = 0.162) were found between HIV-positive
      patients and the control group. No any correlation was determined between all
      three types of electrolytes and the number of CD4+ cells, nor the number of HIV
      virus copies in peripheral blood of patients. Within the HIV-positive group, with
      respect to HAART therapy, no differences were found in the concentration levels
      of salivary magnesium (p = 0.588), nor zinc (p = 0.096). However, the
      concentration levels of salivary calcium were significantly higher in HIV
      positive patients who underwent HAART treatment (p = 0.004). The results of this
      research show that HIV, as a systematic infection, does not cause changes in the
      excretion of magnesium, zinc nor calcium in non-stimulated total saliva.
      Furthermore, it has been proven that HAART treatment does not cause changes in
      the concentration levels of magnesium or zinc, but can cause an elevation in the
      concentration level of saliva, which could be related to the calcium mobilization
      in blood.

PMID- 19408611
TI  - Body size and body composition change trends in preschool children over a period
      of five years.
AB  - The study investigated the changes of body size and composition in the sample of
      296 preschool urban dwelling children aged 6.5 +/- 0.8 years over a period of
      five years. Fourteen anthropometric measures were taken. Body mass index (BMI),
      the sum of skinfolds, the fat percentage and fat-free mass (FFM) were computed.
      The significant changes in body size and composition over the observed period
      were found. A significant increase in height and weight was registered in the
      boys. The average BMI did not change significantly while body fatness was
      significantly enlarged (from 10.79% to 16.96%, P = 0.0001) with no changes in
      FFM. In the girls there were no significant changes in height, weight and BMI,
      while again fatness was significantly enlarged (from 15.5% to even 19.44%, P =
      0.003), with a significantly decreased share of FFM (P < 0.05), primarily due to
      the decrease of the upper limbs' muscular mass. The greatest contribution to the
      discriminant function was obtained by the skinfolds in the boys and by the arm
      length and forearm circumference in the girls.

PMID- 19408612
TI  - Evaluation models of some morphological characteristics for talent scouting in
      sport.
AB  - In this paper, for the purpose of expert system evaluation within the scientific
      project "Talent scouting in sport", two methodological approaches for recognizing
      an athlete's morphological compatibility for various sports has been presented,
      evaluated and compared. First approach is based on the fuzzy logic and expert
      opinion about compatibility of proposed hypothetical morphological models for 14
      different sports which are part of the expert system. Second approach is based on
      determining the differences between morphological characteristics of a tested
      individual and top athlete's morphological characteristics for particular sport.
      Logical and mathematical bases of both methodological approaches have been
      explained in detail. High prognostic efficiency in recognition of individual's
      sport has been determined. Some improvements in further development of both
      methods have been proposed. Results of the research so far suggest that this or
      similar approaches can be successfully used for detection of individual's
      morphological compatibility for different sports. Also, it is expected to be
      useful in the selection of young talents for particular sport.

PMID- 19408613
TI  - The effects of strength training on some parameters of aerobic and anaerobic
      endurance.
AB  - The studies exploring the influence of resistance training on endurance in men
      have produced inconsistent results. The aim of this study was to examine the
      influence of an Olympic weight lifting training programme on parameters of
      aerobic and anaerobic endurance in moderately physically active men. Eleven
      physical education students (age: 24.1 +/- 1.8 yr, height: 1.77 +/- 0.04 m, body
      mass: 76.1 +/- 6.4 kg; X +/- SD) underwent a 12-week, 3 times/wk training
      programme of Olympic weight lifting. Specific exercises to master the lifting
      technique, and basic exercises for maximal strength and power development were
      applied, with load intensity and volume defined in relation to individual maximal
      load (repetitio maximalis, RM). Parameters of both, aerobic and anaerobic
      endurance were estimated from gas exchange data measured during a single
      incremental treadmill test to exhaustion, which was performed before, and after
      completion of the 12-wk programme. After training, there was a small, but
      significant increase in body mass (75.8 +/- 6.4 vs. 76.6 +/- 6.4, p < 0.05) and
      peak VO2 (54.9 +/- 5.4 vs. 56.4 +/- 5.3 mL O2/min/kg, p < 0.05), with no
      significant change of the running speed at the anaerobic threshold (V(AT)) and at
      exhaustion (V(max)) (both p > 0.05). However, there was a significant increase of
      anaerobic endurance, estimated from the distance run above V(AT), from V(AT) to
      V(max), (285 +/- 98 m vs 212 +/- 104 m, p < 0.01). The results of this study
      indicate that changes in both, anaerobic and aerobic endurance due to a 12-wk
      period of strength training in untrained persons can be determined from a single
      incremental treadmill test to exhaustion. The possible causes of those training
      effects include several possible mechanisms, linked primarily to peripheral
      adaptation.

PMID- 19408614
TI  - Physical development and swimming performance during biological maturation in
      young female swimmers.
AB  - The present study analyzed the development of physiological, biomechanical and
      anthropometrical parameters in young female swimmers and assessed the effect of
      these parameters on swimming performance during biological maturation. In total,
      26 female swimmers participated in the study in which data were annually
      collected for two consecutive years. Body composition, basic anthropometrical
      parameters and biological age were measured. During the 400-m front-crawl
      swimming, the energy cost of swimming and stroking parameters were assessed. Peak
      oxygen consumption (VO2(peak)) was assessed by means of the backward
      extrapolation technique recording VO2 during the first 20 sec of the recovery
      period after a maximal trial of 400-m distance. During the 2-year follow-up study
      period, age, height, body mass, body fat %, fat free mass, bone mineral mass,
      total bone mineral density, arm span and biological maturation values
      significantly increased during each year (p < 0.05). The tracking of the physical
      characteristics measured over the 2-year study period was relatively high (r >
      0.694), except for the body fat% (r > 0.554). The tracking of the Tanner stages
      was also high (r = 0.759-0.780). Stepwise regression analyses showed that
      biomechanical factors (R2 > 0.322; p < 0.05) best characterized the 400-metre
      swimming performance in young female swimmers, followed by bioenergetical (R2 >
      0.311; p < 0.05) and physical (R2 > 0.203; p < 0.05) factors during all three
      measurement times.

PMID- 19408615
TI  - The impact of specific motoricity on karate performance in young karateka.
AB  - The aim of the study was to assess interdependence of specific motor abilities
      (situation karate tests) and motor skills (karate techniques), and karate
      performance (fighting efficiency) in under-sixteen male karateka aged 11-12 and
      13-14 years. A battery of 5 situation motor tests were applied and 6 basic
      elements of karate technique evaluated in a sample of 20 male karateka aged 11-12
      and 20 male karateka aged 13-14 years. Three criterion variables were formed: 1)
      one factor as a factor of general technical efficiency in karate was isolated by
      factor analysis of 6 karate techniques; 2) cumulative evaluation of 2 kate as
      kate performance; and 3) total score assessment based on success achieved at
      national karate championships as contest efficiency (fighting efficiency).
      Regression analysis revealed the frequency of gedan barai blockade performance to
      be the superior predictor of technical efficiency, kate performance and contest
      success in karateka aged 11-12, whereas the speed of the gedan barai-jaku zuki
      (block-kick) combination performance and specific agility (sidewise mobility)
      were superior predictors of performance in karateka aged 13-14. Of the karate
      techniques (kicks) used, the quality of jaku zuki kick performance was the
      superior predictor of contest efficiency in karateka aged 11-12, and the quality
      of the jaku zuki-mawashi geri and kizame zuki-jaku zuki combination performance
      in karateka aged 13-14.

PMID- 19408616
TI  - Sex differences in morphological dimensions in twelve-year-old children from
      Imotska krajina.
AB  - The aim of the study was to identify and compare morphological characteristics of
      12-year-old male and female children from Imotska krajina. The structure of a set
      of 23 morphological space variables were determined in a sample of 75 male and 67
      female children by use of factor analysis for each sex in separate. Factor
      structure showed two basic superior latent dimensions responsible for directly
      measurable manifestations of morphological parameters in both male and female
      children. One of these two dimensions behaved as a general mechanism of growth
      and development, whereas the other showed a bipolar pattern. Bipolarity was
      almost exclusively determined by adipose tissue on one pole, and by skeletal
      longitudinal growth on the opposite pole. Rotation of the main components to
      varimax position yielded two morphological dimensions that were well balanced in
      both sexes (slightly better in girls); besides the predominant increase in
      adipose tissue, one of these dimensions was also responsible for the development
      of muscular tissue and skeletal transverse development, whereas the other was
      responsible for skeletal transverse development and muscular tissue development
      in addition to the predominant longitudinal skeletal growth. These observations
      suggested two developmental processes, i.e. transverse morphological development
      (first factor) and longitudinal morphological development (second factor), to be
      almost equally involved in the morphological development of 12-year-old male and
      female children. These developmental processes are highly genetically determined
      and can only in part be explained by the intensity of kinesiologic engagement.
      Based on the morphological structures defined, discriminative function of the
      morphological space primarily differentiated two developmental processes, i.e.
      longitudinal skeletal development (hand length in particular) in female children
      relative to transverse skeletal development (knee diameter in particular) in male
      children, pointing to the presence of full-swing puberty in female children,
      while yet to be expected in male children; thereafter, the differences in the
      ectomesomorphic morphological characteristics would be by far more pronounced in
      favor of male children.

PMID- 19408617
TI  - Dental status as a quality control health care parameter for children with
      disabilities.
AB  - The aim of this study was to determine the level of dental health condition in
      children with disabilities and to find out weather dental health status might be
      used as a quality control parameter regarding overall health care for disabled
      children. Disabled and healthy children from 3 to 17 years old were examined.
      There were 86 boys and 34 girls in each group. Dental health status was evaluated
      using the World Health Organization diagnostic criteria for decayed, missing and
      filled teeth. The relations between mean decayed, missing and filled teeth index
      for primary, mixed and permanent dentition showed no statistically significant
      differences among groups. Our results showed that disabled children have evenly
      level of dental caries as their healthy peers. One can conclude that organized
      health care for disabled children have positive influence on dental care, too.
      Furthermore, dental status as an indicator of dental care level might be used as
      a parameter for quality control regarding overall health care for disabled
      children.

PMID- 19408618
TI  - Regression analysis of the symptoms.
AB  - Stomatopyrosis of 'burning mouth' syndrome, in a narrower sense of definition, is
      a condition characterized by sensation of burning and heating in mouth, despite
      its normal mucosa. This research has been directed towards treatment of
      stomatopyrosis, putting emphasis on the implementation of psychopharmacotherapy
      and psychotherapy. The research was conducted on altogether 120 respondents
      suffering from stomatopyrosis. The respondents were divided into two equal
      groups: each one comprising 60 members. All the respondents were treated by means
      of a standard topical therapy. All the patients were assessed clinically and by
      means of psychological tests measuring depression and anxiety four times: once
      before the treatment, after one month, after two months and after four months
      since the beginning of the treatment. The acquired data were afterwards
      statistically processed. Our research led to the conclusion that stomatopyrosis
      occurs with elderly people, primarily women. Regarding their occupation, majority
      of the respondents were clerks, followed by retirees. The burning sensation in
      mouth was present with all the respondents, the dominating site being the lips,
      while the nature of sensation was reported as mostly unbearable. Anxiety, tension
      and stress tend to aggravate the symptoms. When grading the symptoms on VAS, i.e.
      visual analogous scale, the subjective assessment of symptoms was marked as 7-8
      cm, which shows a high degree of burning sensation. According to our study, the
      quantity of saliva, which was at the beginning of the research slightly
      decreased, normalized after the treatment. Apart from the clinical investigation
      of stomatopyrosis, we applied Depression and Anxiety questionnaires. During the
      therapy, the results of the depression test have shown a decrease in depression
      (from 56.7% to 0.00%), which is particularly apparent in the group treated by
      autogenic training and in the first group of respondents, i.e. the one treated
      with antidepressants. The Anxiety tests have shown a higher percentage and
      intensity of anxiety with men (62.5%, as opposed to women - 32.5%) in the
      beginning, which has dropped to 7.5% with men during the treatment and 8.8% with
      women. Clinical presentation of stomatopyrosis has also apparently improved. This
      improvement in clinical symptoms and psychological condition of patients is
      statistically significant. On the basis of our research, we have concluded the
      following: the comorbidity of stomatopyrosis with the phenomena of anxiety and
      depression proves that, among other factors, there is a psychogenic aetiology of
      this disease. Further research should provide answers to the questions whether
      stomatopyrosis is a psychosomatic or a conversive disorder Antidepressants and
      anxiolytics have an important role in the therapy of stomatopyrosis. Autogenic
      training, which is a psychotherapeutic anxiolytic technique, is a therapy of
      choice for stomatopyrosis, which contributes not only to the elimination of oral
      complaints, but to the emotional rehabilitation of the patients as well.

PMID- 19408619
TI  - The influence of Healozone on microleakage and fissure penetration of different
      sealing materials.
AB  - The preventive effect of sealing materials depends on ability to penetrate into
      the fissures, and microleakage absence, resulting with better clinical success.
      The aim of present study was to investigate the influence of ozone on
      microleakage and penetration of nanoparticle fissure sealing resin and flowable
      composite, and quantitative and qualitative analysis of microleakage. Forty
      extracted non carious third molars were randomly divided in 4 groups. Group A:
      KaVo Healozone and Grandio Seal; Group B: Kavo Healozone and X-Flow; Group C:
      Grandio Seal; Group D: X-Flow. The teeth were thermocycled, immersed in 5%
      methylene dye for 24 hours, and sectioned with precision saw. The total of 149
      slices were analysed with stereomicroscope for microleakage and sealant
      penetration. According to qualitative scores, there is a significant difference
      between groups C and D, group C showing better results. According to quantitative
      scores, there are no statistical differences between the groups. The treatment of
      the enamel with KaVo HealOzone after etching does not affect either microleakage
      or penetration proportion of flowable composite or sealing resin. There is no
      statistically significant difference in a degree of penetration between different
      groups of sealing materials. Groups of materials with flowable composite in
      combination with an adhesive system show a good degree of penetration into the
      fissure and low microleakage meaning that they can be used as a fissure sealing
      materials.

PMID- 19408620
TI  - Is sports recreation important to university students?
AB  - The aim of this research is to examine university students' attitudes on
      recreational exercise. The sample included 473 students from the University of
      Zagreb. We analyzed the data by analysis of frequency and a statistical method
      called "Relation model of action". The results indicated that there were two
      general courses in students' attitudes on recreation activities. The first course
      represents general values and the second course reflects the attitudes on
      specific sports and recreational activities. It can be concluded that university
      students recognize the importance of exercise but they do not understand its real
      meaning and they do not exercise regularly. Therefore, it is important to foster
      positive attitudes towards exercise early in youth, which would allow young
      people to preserve the healthy habit of exercise throughout their whole life.
      There is a need for quality system of education, which would start early in
      childhood.

PMID- 19408621
TI  - Migraine and tension-type headache in medical students: a questionnaire study.
AB  - The purpose of our study was to perform an epidemiological study of migraine and
      tension-type headache (TTH) in medical students (MS) at University of Zagreb
      Medical School and to determine whether there are differences in prevalence,
      trigger factors, health care utilization and self-medication between sixth year
      and first year MS. This study included 314 students who answered a questionnaire
      from October to November 2003. The prevalence of migraine was 8.86% in first year
      students and 10.90% in sixth year students while the prevalence of TTH was 60.13%
      and 57.69% respectively. Female students suffered from migraines significantly
      more often than male students (p = 0.017). Female students with migraine linked
      their headaches to their menstrual cycle significantly more often than female
      students with TTH (p = 0.011). Significantly more first year students have
      visited a doctor concerning their headaches than sixth year students. Also, there
      is a significantly higher level of self-medication amongst sixth year students.
      Our study has shown that a relatively large percent of MS suffers from TTH; a low
      percent is seeking medical advice for headaches, the majority is self-medicated,
      and an unacceptably low percentage is taking triptans for migraine.

PMID- 19408622
TI  - Lumbosacral radiculopathy--factors effects on it's severity.
AB  - Want to demonstrate factors which effect appearance and severity of lumbosacral
      radiculopathy. We analysed 100 electromyoneurographically examined patients.
      Patients were categorised on bases of their BMI (body mass index), sex, age, job
      type (physical or intellectual job), and chronic diseases (diabetes mellitus,
      arterial hypertension and hyperlipidemia). Data were evaluated using the chi2
      test with the significance of p < 0.05. Obese patients had severe radiculopathy
      more often than non-obese patients (p < 0.044). Severe radiculopathy appeared
      more frequently in male (p < 0.001), elderly patients (p < 0.023), and patients
      doing physically intensive jobs (p < 0.002). No statistic significance was found
      in relationship between patients suffering from diabetes mellitus, arterial
      hypertension, and hyperlipidemia, and the severity of lumbosacral radiculopathy.
      Obese patients, males, elderly patients, and patients doing physically intensive
      jobs are at a bigger risk of suffering from severe radiculopathy. Diabetes
      mellitus, arterial hypertension, and hyperlipidemia do not influence the severity
      of lumbosacral radiculopathy.

PMID- 19408623
TI  - Euthanasia of patients with the chronic renal failure.
AB  - This study deals with frequency and form of euthanasia in dialysis patients with
      chronic renal failure (CRF) in Bosnia and Herzegovina (B&H) within the period
      from 2000 to 2006. Of total number of 2700 patients on dialysis we examined n =
      753 of them. Examinees with the Balkan Endemic Nephropathy (BEN) (n = 348) were
      in the first group, and the Control group was formed of patients with other
      diseases (n = 405). In this study the following methods were used: adapted
      Questionnaire from the Renal Registry of B&H, Beck's Anxiety Inventory (BAI),
      Hamilton's Depression Rating Scale (HDRS) and Mini-Mental Scale of Estimation
      (MMSE). Age of the BEN group of patients ranged: 64.77 +/- 8.86 and the control
      one 53.85 +/- 3.60. Multivariate analysis for the BEN group with passive
      euthanasia was: 0.760 (95%, CI = 0.590-0.710) (p = 0.001) and for the active one
      was 0.450 (95%, CI = 0.125-0.510 (p = 0.001). Euthanasia is associated with the
      rural life and renal heredity, and psychological BAI scale-total, HDRS-total and
      MMSE-total. For the BEN group passive euthanasia is 3.75% as well as active
      0.86%. The findings stressed that euthanasia of dialysis patients requires better
      nephrological-psychiatric control and social care in B&H as well as complete
      program for the CRF samples protection too.

PMID- 19408624
TI  - Genitourinary diseases prior spontaneous abortion as a risk factor for recurrent
      pregnancy loss.
AB  - The etiology of recurrent spontaneous abortion (RSA) is still unexplained. Many
      couples do not find the cause of their RSA at all. The purpose of this research
      was to evaluate the association between recurrent pregnancy loss and previous
      (cured prior to pregnancy) acute/chronic genitourinary infections in both
      parents. Couples (226) having two or more (up to six) spontaneous abortions were
      analyzed in this retrospective case-control study. The control group consisted of
      124 couples with neither miscarriages nor complicated pregnancies in their past.
      The data (serum immunological markers, karyotype, flow cytometry data, PHD) were
      collected from their medical charts. It was found that there was no statistically
      significant difference in average weeks of pregnancy in which the second, third
      and fourth abortion occurred. There was a statistically significant difference in
      previously experienced genitourinary infections between women from the RSA group
      and the control group, as well as for men from the RSA group and the control
      group. It can be concluded that past infections of the maternal and/or paternal
      genitourinary system may be the causal factor for recurrent pregnancy loss and
      can also pre-determine women that are of greater susceptibility to preterm
      pregnancy. Therefore the genetic counseling of couples should include thorough
      medical and family history of both partners and their first- and second-degree
      relatives in conjunction with typical medical examination.

PMID- 19408626
TI  - Operative complications and results of the "SPARC" procedure for stress urinary
      incontinence.
AB  - The aim of this study was to determine the efficacy and operative complications
      of the suprapubic arc (SPARC) procedure in stress incontinent women with and
      without previous anti-incontinence surgery. One-hundred and twenty-one patients
      with stress urinary incontinence (SUI) were treated with SPARC for correction of
      urethral hypermobility (N = 65) and intrinsic sphincter deficiency (N = 56)
      between August 2002 and February 2007. The long-term surgical results, operative
      complications (bladder injury, retropubic hematoma, de novo urgency and urinary
      infection) and patients' satisfaction were assessed. The overall complication
      rate was 9.9% (12/121). The perioperative complication rate was 1.7% including 2
      urinary bladder injuries. Significant difference in the overall complications
      rate was detected between women with and without previous surgery (23/45, 51.1%
      vs. 6/108, 5.5%, chi2 = 49.89, P < 0.001). The overall postoperative complication
      rate was 8.3% (10/121) including 4 de novo urgencies, 4 urinary infections and 2
      retropubic hematomas. There were 3 patients with postoperative urinary retention
      managed conservatively, without voiding difficulties on control visits. The
      objective cure rate after the follow-up was 86.8% (105/121). In patients with SUI
      and without preceding vaginal operations SPARC is a good method with low
      incidence of perioperative complications, promising long-term results and high
      patient satisfaction.

PMID- 19408625
TI  - Influences of twilight on diurnal variation of core temperature, its nadir, and
      urinary 6-hydroxymelatonin sulfate during nocturnal sleep and morning drowsiness.
AB  - This study aimed at elucidating the physiological significance of dusk and dawn
      in the circadian rhythm of core temperature (T(core)) and urinary 6
      hydroxymelatonin sulfate in humans during sleep and the waking sensation just
      after rising. Seven female and four male students served as participants.
      Participants retired at 2300 h and rose at 0700 h. They were requested to sit on
      a chair and spend time as quietly as possible during wakefulness, reading a book
      or listening to recorded light music. Two lighting conditions were provided for
      each participant: 1) Light-Dark (LD)-rectangular light change with abrupt
      decrease from 3,000 lx to 100 lx at 1800 h, abrupt increase from 0 lx to 3,000 lx
      at 0700 h. 2) LD-twilight light change with gradual decrease from 3,000 lx to 100
      lx starting at 1700 h (twilight period about 2 h), with gradual increase from 0
      lx to 3,000 lx starting at 0500 h (twilight period about 2 h). The periods of 0
      lx at night were from 2300 h to 0700 h on the first day and from 2300 to 0500 h
      on the second day. Nadir time advanced significantly under the influence of the
      LD-twilight condition. The amount of 6-hydroxymelatonin sulfate in urine
      collected at 0200 h was significantly higher under LD-twilight in comparison with
      LD-rectangular light. Morning drowsiness tended to be lower under LD-twilight.
      Our results suggest that in architectural design of indoor illumination it is
      important to provide LD-twilight in the evening and early morning for sleep
      promotion in healthy normal people and/or light treatment in elderly patients
      with advanced dementia.

PMID- 19408627
TI  - Adolescents eating behavior, body image and psychological well-being.
AB  - This study focuses on the middle school students in the Croatian region of
      Dalmatia. The survey was designed to examine adolescent eating behavior as it
      relates to body image and psychological well-being (self-esteem, life
      satisfaction and stress) in relation to body mass index; BMI. Differences among
      participants in food intake were examined according to demographic variables and
      eating behavior (regular food intake or dieting) as well. Psychological variables
      were highly associated with dieting among adolescents of both genders. The
      adolescents who were dieting reported significantly lower self-esteem, lower life
      satisfaction and lower body-image satisfaction, higher rate of stress and higher
      rate of body mass index (BMI) when compared to non-dieters. This study confirms
      that a rather large percentage of adolescent girls of low socioeconomic status
      engage in dieting when trying to lose weight, which may seriously damage their
      developmental growth.

PMID- 19408628
TI  - Indications for psychiatric safety measures: a retrospective study.
AB  - The aim of this article has been designed to investigate the influence of
      particular diagnostic categories on recommendations for safety measures, and to
      investigate the impact of constellatory factors, as the states of acute
      alcoholism, acute intoxication by psychoactive drugs and intense affect, on the
      recommendations for safety measures. The sample consisted of 120 examinees
      forensically expertised at the Center for Forensic Psychiatry of the Psychiatric
      Hospital Vrapce in the period from January 1, 1998 to December 31, 1999, and
      evaluated as less responsible according to the new Penal Code. All the examinees
      had the same legal presumptions for safety measures (decreased responsibility).
      The sample was divided into two groups: a group of examinees for whom a safety
      measure had been recommended and a group without such recommendations. The basic
      methodological instrument was a specially designed questionnaire with 137 items.
      Regarding socio-demographic characteristics, no statistically significant
      differences existed between the two groups taking into account age, gender, level
      of education and marital status. The diagnosis of personality disorder as the
      first one, did not influence recommendations for safety measures. Alcohol and
      drug abuse were statistically significantly present in the group with recommended
      measures as second diagnoses, and besides influencing responsibility, had an
      impact on the recommendation of safety measures. An intense affect influenced the
      reduction of responsibility, but not the suggestion of safety measure, while
      alcohol and drug intoxications, besides affecting responsibility, had an impact
      on the suggestion of safety measure. The decisive impact of dependence influenced
      the recommendation for safety measures.

PMID- 19408630
TI  - Self-perception of drug abusers and addicts and investigators' perception of
      etiological factors of psychoactive drug addiction.
AB  - The aim of this study was to compare investigators' perception of three most
      important etiological factors for drug addiction and drug abuse with the self
      perception of heroin addicts and drug abusers who used cannabis products and/or
      ecstasy. The study included 207 heroin addicts (mean age, 26.7 +/- 5.8 years) and
      238 drug abusers (mean age, 19.3 +/- 1.9 years). Each study participant selected
      the three most important etiological factors for drug addiction or drug abuse
      from the list in the Pompidou questionnaire according to his or her perception.
      An investigator also selected the three most important etiological factors for
      drug addiction or abuse according to his or her perception for each study
      participant. The self-selected factors were compared with those selected by the
      investigators. Heroin addicts most often selected hedonism as the first (n = 97
      [46.9%]) and the second (n = 87 [42.0%]) most important factor for starting using
      drugs, whereas family reasons were most often selected as the third most
      important factor (n = 58 [28.0%]). Cannabis and ecstasy abusers most frequently
      selected hedonism as the first (n = 149 [62.6%]), second (n = 128 [53.8%]), and
      third (n = 76 [31.9%]) most important factor for starting using drugs. According
      to investigators' perception, family reasons were the first most important
      etiologic factor in both heroin addicts (n = 93 [44.9%]) and drug abusers (n =
      144 [60.5%]). Psychological reasons were significantly more often selected as the
      first most important factor for heroin addiction than for cannabis or ecstasy
      abuse by both participants and investigators (P < 0.001 for both). Also,
      according to investigators' perception, the lack of knowledge was significantly
      more frequent as the second most important factor in heroin addicts than in
      cannabis or ecstasy abusers (55 [26.6%] vs 19 [8.0%], respectively; P < 0.001).
      Drug addicts and drug abusers considered hedonism the most important reason for
      starting drug use, whereas investigators considered family reasons to be the
      primary reason. Both factors seemed to play the crucial role in the development
      of both drug addiction and drug abuse.

PMID- 19408629
TI  - Problems in the current psychiatry residency training program in Croatia:
      residents' perspective.
AB  - The aim of this study is to evaluate the quality of the current residency
      training in psychiatry in Croatia using parameters of professional achievements
      of residents and their subjective evaluations of the residency training that is
      being offered. 66 residents from 15 Croatian psychiatric hospitals, clinics and
      wards in general hospitals fulfilled the questionnaire constructed to obtain
      information about the profile of psychiatry residents in Croatia, parameters of
      educational quality and evaluation of offered residency training as seen by
      residents. We interviewed 89% of all residents that had a trainee status in
      September and October 2006 in Croatia (66 out of 74). Study results indicate that
      Croatian psychiatry residents are derived from a pool of very good medical
      students and the majority is engaged in postgraduate studies and research
      activities and shows high interest in specific psychiatric fields such as
      psychotherapy and clinical psychiatry. Most of participants are only partially
      satisfied with the residency training that is being offered and feel that most
      problems reside from the lack of practical psychotherapy, the inefficiency of the
      mentorship system and the lack of funding resources. The results of this study
      revealed the major problems of psychiatry residents in Croatia. Following those
      results, we will perform the study that would include mentors and supervisors
      from different Croatian psychiatric centers. That could enable the development of
      specific interventions with aim to improve current residency training in Croatia.

PMID- 19408631
TI  - Characteristics of patients who committed suicide during hospitalization in
      Psychiatric Hospital "Vrapce" in the period 1996-2006.
AB  - The aim of this study was to determine the characteristics of psychiatric
      inpatients who committed suicide in the Vrapce Psychiatric Hospital with respect
      to clinical, ethical, and legal context. The study included all patients
      hospitalized in the Vrapce Psychiatric Hospital between 1 January 1996 and 31
      December 2006 who committed suicide (n = 25). The suicide rate in the observed
      period was 32.9 per 100.000 (suicide coefficient, 50), which is similar that in
      general population. Based on the characteristics of hospitalized patients who
      committed suicide, we obtained a typical profile as follows: a middle-aged
      person, single, unemployed, repeatedly hospitalized, with schizophrenia and a
      history of suicide attempts, committing suicide using a violent method after more
      than three weeks of hospital treatment. If further prevention of hospital suicide
      will be treated as a legal rather than medical issue, the hospital atmosphere
      would be totalitarian rather than therapeutic. The success of psychiatric
      treatment is the perception of both of these aspects of suicide as well as their
      efficient balancing.

PMID- 19408632
TI  - Outpatient utilization of psychopharmaceuticals: comparison between Croatia and
      Scandinavian countries (2001-2003).
AB  - The aim was to estimate outpatient consumption of psychotropic drugs in Croatia
      in correlation with Scandinavian countries. Data on drug utilization, from Zagreb
      Municipal Pharmacy, were used to calculate the number of defined daily doses
      (DDD) and DDD per 1000 inhabitants per day (DDD/TID) using Anatomical-Therapeutic
      Chemical methodology (ATC) by WHO. Data of the Nordic Medico-Statistical
      Committee were used for Scandinavian countries. In Zagreb, total utilization of
      psychopharmaceuticals of 144.9 DDD/TID in 2001, 148.9 DDD/TID in 2002 and 141.9
      DDD/TID in 2003. The anxiolytic/antidepressant ratio decreased in Zagreb by
      35.19% (7.19 in 2001 and 4.66 in 2003), whereas in Scandinavian countries it
      showed a constant rate (0.7 in Finland, 0.4 in Denmark and Norway, and 0.3 in
      Sweden). The three-year utilization patterns show that Croatia has been ever more
      closely following Scandinavian countries although there have been a notable
      differences between Croatia and Scandinavian countries.

PMID- 19408633
TI  - The efficacy of a brief supportive psychodynamic therapy in treating anxious
      depressive disorder in Daily Hospital.
AB  - Study objective is to determine the efficacy of brief supportive psychodynamic
      therapy in treating anxious-depressive disorder in Daily hospital within the
      Psychological Medicine Clinic. The study comprised a total of 45 male subjects,
      in which an admission to the Daily Hospital was indicated. On the occasion of the
      hospital admission, as well as following the completion of a one month-lasting
      partial hospitalisation within the Daily Hospital, the subjects had undergone
      testing using a number of psychological instruments. There weren't established
      statistically significant differences in clinical presentations of the treated
      patients. A partial, one month-lasting hospitalisation, did not yield any changes
      in clinical presentation an anxious-depressive disorder. Due to the fact that
      this psychotherapeutic method should be applied for quite some time in order to
      yield results, and is not expected to be effective in a close range, a one-month
      lasting treatment is definitely not long enough to be effective.

PMID- 19408634
TI  - Mast cell tumor in dogs--incidence and histopathological characterization.
AB  - Incidence of mast cell tumors, their distribution according to sex, breed, age
      and localisation in Croatia is not established yet. Also, the statistical
      significance of the various histopathological parameters according to Patnaik's
      scheme, in the diagnostics of the tumor grade was not performed. Investigation
      analysed mast cell tumors histopathologicaly characterized at the Department of
      General Pathology and Pathological Morphology of the Veterinary Faculty Zagreb
      from January 1st 2002 to December 31st 2006. Sex, age, breed, localisation and
      tumor grade of each animal with tumor was recorded and statisticaly evaluated.
      Each histopathological variable was scored and compared with tumor grade. In the
      analyzed period, totally 1630 tumors were recorded, and mast cell tumors were
      found in 106 animals or in 6.5% of all cases. With statistically significant
      difference, this tumor was found in more cases in male dogs, and average age was
      6.96 years. Boxers and retrievers were most frequent breeds, and localization was
      mostly on legs. Grade I tumor was found in 15.09%, grade II in 44.34% and grade
      III in 28.3% of animals. There were no significant correlations between tumor
      grade and age, breed, sex or localization. Considering the lesion scores compared
      with grade, statistically significant differences were found in cell shape,
      number of nucleoli, anisocytosis, anisokariosis, karyomegaly, mitoses, necroses,
      hemorrhages, cellularity, cell borders and collagenolysis.

PMID- 19408635
TI  - Splintering of tourism market: new appearing forms of cultural tourism as a
      consequence of changes in everyday lives.
AB  - Within the concept of cultural tourism, this article defines relatively new
      concepts of creative and hobby tourism, which are detected as recent niche
      markets. Cultural tourism is a narrow specialized market, while creative and
      hobby tourism relate to even more specialized segments. Even these specialized
      forms of tourism have their market whose growth is very probable taking into
      account changes in everyday work as well as changes in the values of human
      activity in general. These changes reflect also the sector of tourism, which is
      obvious in the ever growing splintering of tourism market as well as of tourism
      forms. The article reviews theoretical concepts of cultural, creative and hobby
      tourism as to prepare the basis for applied tourist programmes. It looks into the
      history of cultural tourism as to see what changes occurred and brought it to
      life. Changes that have taken place in everyday lives of people and the impact of
      everyday free time activities on tourism are also analysed. Further splintering
      of the cultural tourism sector is noticed and cultural tourism sub-forms are
      detected by analysing some of the leading home style and creativity magazines.
      The article also proposes possible application of push/pull factors to
      creative/hobby tourism.

PMID- 19408636
TI  - Posttraumatic stress disorder in women--experiences form the Psychiatric Clinic,
      University Hospital Center Zagreb, Croatia.
AB  - Posttraumatic stress disorder (PTSD) is an anxiety disorder that develops after a
      severe traumatic event or experience. Lifetime prevalence rate in the European
      population is 1.9 % and it is higher for women (2.9%) then for men (0.9 %). The
      aim of this study was to examine rates and sociodemographic and clinical
      characteristics of women with PTSD who were hospitalized at the Psychiatric
      clinic of University Hospital Center in Croatia over the years 1990-2007. Data
      were gathered retrospectively from the medical charts. We found that 67 women
      were diagnosed with PTSD which is 0.58% of all admissions over these years.
      Majority suffered from comorbid depression (N = 51) and various somatic
      conditions, especially malignant gynecological tumors (N = 23). No significant
      differences were found in distribution of PTSD symptoms in relation to the combat
      vs. civilian trauma. We found that patients with combat trauma often suffer from
      comorbid depression, while those with civilian traumas more often reported
      somatic conditions, especially malignant gynecological tumors. Our institution is
      a speciality clinic at a tertiary care medical center which tends to accumulate
      patients with serious forms of the disorder, and therefore our results can not be
      generalized to other settings involved in working with women with PTSD. Our
      results indicate that psychiatrists' assessment of female patients should
      inevitably include lifetime traumatic experiences, and among those with PTSD,
      special attention should be paid to comorbid depression and malignant tumors.

PMID- 19408637
TI  - Epidemiology and clinical characteristics of thyroid dysfunction in children and
      adolescents with type 1 diabetes.
AB  - The aim of the study was to evaluate the natural course and potential risk
      factors of autoimmune thyroiditis (AIT) and thyroid dysfunction, and their
      influences on growth and glycemic control in children and adolescents with type 1
      diabetes mellitus (T1D). The study comprised 148 subjects (age range 1-21 years;
      males 51%) with T1D. During the interval of 12 years serum levels of thyroid
      peroxidase (anti-TPO) and thyroglobulin (anti-TG) autoantibodies, thyroid
      stimulating hormone (TSH) and tyroksine (T4), were screened annually. Height,
      weight, body mass index (BMI), glycosylated hemoglobin (HbA1c), insulin dose and
      the number of severe hypoglycemic episodes, were recorded every 3 months. The
      mean follow-up was 7 +/- 4.1 years. Prevalence of AIT in subjects with T1D was
      15.5%. It was significantly higher in girls (21.9% vs. 9.3%; p = 0.03). The mean
      age at AIT onset was 11.5 +/- 5.2 years. The mean interval between negative and
      positive AIT screening was 2.5 +/- 2.3 years. Cumulative incidence of AIT after 6
      years of T1D duration was significantly higher in girls (30% vs. 15%; p = 0.03).
      Prevalence of hypothyroidism was 8.1% with no significant differences in sex
      distribution. Prevalence of hypothyroidism among subjects with elevated serum
      thyroid antibodies was 52.2% with significant male preponderance (85.7% vs.
      37.5%; p = 0.005). There were no subjects who developed hypothyroidism in absence
      of thyroid antibodies. Cumulative incidence of hypothyroidism after 3 years from
      the moment of thyroid antibodies appearance was 55% with significant male
      preponderance (85% vs. 40%; p = 0.005). The mean interval between T1D onset and
      hypothyroidism development was 3.3 +/- 2.5 years, and between thyroid antibodies
      appearance and hypothyreoidism development was 1.7 +/- 1.2 years. The mean age at
      hypothyroidism onset was 12.7 +/- 5.3 years. There were no differences in growth
      and metabolic control between patients with and without AIT. The results of the
      present study confirmed frequent occurrence of AIT and thyroid dysfunction in
      subjects with T1D. The number of newly diagnosed subjects with AIT reached the
      peak at the age of puberty. Girls were significantly more predisposed to AIT at
      any age while amongst subjects with elevated thyroid antibodies boys developed
      hypothyroidism more frequently. Annual screening of thyroid antibodies in all
      patients with T1D is recommended, while serum TSH level should be measured in
      patients with detected thyroid antibodies.

PMID- 19408638
TI  - Neuropsychiatric systemic lupus erythematosus: diagnostic and clinical features
      according to revised ACR criteria.
AB  - Neuropsychiatric disorders appear in about 70% of the patients diagnosed with
      systemic lupus erythematosus (SLE). The aim of this study was to evaluate
      morphological and functional abnormalities of central nervous system (CNS) in SLE
      patients with neuropsychiatric manifestations (NP) of disease by testing their
      relationship. We tested 10 patients (9 females, 1 male) with clinical
      manifestations of neuropsychiatric systemic lupus erythematosus (NP-SLE). That
      means clinical evaluation of symptoms, standard immunoserological tests,
      electroencephalogram (EEG), component of audio--evoked potentials P300, MMPI-202
      test, Rey Complex Test and magnetic resonance imaging (MRI). MRI abnormalities
      were seen in all of our patients, while in 9 patients abnormalities in
      neuropsychological and neurophysiologic tests have been proved. The most common
      structural brain change, detected by MRI, was cortical atrophy (in 8 out of 10
      patients). According to revised classification of the American College of
      Rheumatology (ACR) NP-SLE, the most frequent disorder was cognitive dysfunction
      (in 9 out of 10 patients). Cortical atrophic brain changes have been established
      in 7 out of 9 patients with cognitive dysfunction. Because of already known
      correlation of cortical atrophy with cognitive dysfunction in SLE patients,
      without neuropsychiatric manifestation, we can conclude that neuropsychological
      examination is required in every patient with systemic lupus erythematosus.

PMID- 19408639
TI  - Acute tonsillopharyngitis in a family practice in Mostar, Bosnia and Herzegovina.
AB  - The aim of this study was to examine the characteristics of acute
      tonsillopharyngitis diagnosis and treatment in the family care physicians in
      Mostar, Bosnia and Herzegovina. All patients diagnosed with acute
      tonsillopharyngitis in the Center of Family Medicine in Mostar in 2005 and 2006
      were included in this study. Data were collected from medical records, including
      age and sex, month in which they visited their physician, symptoms and signs that
      they had (McIsaac's clinical score was calculated accordingly) and treatment.
      Results showed that there were no gender differences regarding diagnosis. Mean
      age was 32.6 +/- 16.9 years. The most patients were recorded during the January
      March period. Total of 65.6% patients received antibiotic treatment.
      Phenoxymethylpenicillin, considered as the recommended antibiotic was used in
      46.3% cases only. In conclusion, this first critical assessment of the existing
      family practice records on treating patients with tonsillopharyngitis suggested
      that physicians have to be more critical when treating patients with this
      diagnosis and that the knowledge and treatment of patients with pharyngitis need
      to be continuously improved in general medical practice.

PMID- 19408640
TI  - Postoperative morbidity and histopathologic characteristics of tonsillar tissue
      following coblation tonsillectomy in children: a prospective randomized single
      blind study.
AB  - The aim of this prospective randomized single blind study was to determine the
      depth of thermal damage to tonsillar tissue due to coblation, and to compare it
      with thermal damage to tonsillar tissue following conventional tonsillectomy; to
      correlate the depth of thermal damage to tonsillar tissue with the parameters of
      postoperative morbidity, to compare intraoperative blood loss, postoperative pain
      severity, time to resuming normal physical activity, and incidence of
      postoperative bleeding between two groups of tonsillectomized children aged up to
      16 years. 72 children aged 3-16 years scheduled for tonsillectomy randomly
      assigned into two groups submitted either to conventional tonsillectomy with
      bipolar diathermy coagulation or to coblation tonsillectomy, with a 14-day follow
      up. Statistically significant differences were observed in the depth of thermal
      damage to tonsillar tissue (p < 0.001), intraoperative blood loss (p < 0.004), in
      postoperative pain severity (p < 0.05) and in time to resuming normal physical
      activity between the two groups (p < 0.001). There was no case of reactionary or
      secondary bleeding in either group. In this paper for the first time we have
      correlated postoperative morbidity and thermal tissue damage: less thermal damage
      is associated with less postoperative morbidity.

PMID- 19408641
TI  - Intraperitoneal analgesia for laparoscopic cholecystectomy: bupivacaine versus
      bupivacaine with tramadol.
AB  - The type of pain after laparoscopic surgery differs considerably from that seen
      after laparotomy. Whereas laparotomy results mostly in parietal pain, patients
      after laparoscopic cholecystectomy complain more of visceral pain results from
      the stretching of intraabdominal cavity, peritoneal inflammation and phrenic
      nerve irritation caused by residual carbon dioxide in the peritoneal cavity.
      Intraperitoneal (IP) administration of some drugs can be effective for pain
      relief after laparoscopic surgery. The purpose of this study was to asses the
      effects of intraperitoneal application of bupivacaine or bupivacaine in
      combination with tramadol on pain relief after laparoscopic cholecystectomy.
      After informed written consent and local ethic committee approval, ninthy
      patients of ASA I and II grade undergoing elective laparoscopic cholecystectomy
      for cholelythiasis were recruited in the study. At the end of laparoscopic
      cholecystectomy 30 patients in each group received 50 mL saline 0.9% (group C),
      bupivacaine 0.25% (group B) or bupivacaine 0.25% with tramadol 100 mg (group T).
      VAS pain was estimated at 30 minutes, 1, 2, 4 and 24 hours after surgery.
      Postoperative analgesic requires were also assessed. Pain scores were
      significantly lower in group receiving the IP bupivacaine with tramadol and
      bupivacaine compared to saline group. Intraperitoneal applications of these drugs
      reduced consumption of supplementary postoperative analgesic medication.
      Intraperitoneal administration of bupivacaine with tramadol and bupivacaine are
      simple to use and effective in a reduction ofpain after laparoscopic
      cholecystectomy. In our study we found no differences between bupivacaine with
      tramadol and bupivacaine in postoperative VAS score and analgesic requirements.

PMID- 19408642
TI  - Biopsychosocial model--the integrated approach to health and disease.
AB  - The biomedical model of health and disease dominates in current medical practice.
      The model attributes key role to biological determinants and explains disease as
      a condition caused by external pathogens or disorders in the functions of organs
      and body systems. Such an approach has its historic justification and has proved
      effective in the control of massive infectious diseases. However, now that
      chronic non-infectious diseases prevail, its efficacy has not only become
      questionable, but also the issue has been raised of its economic justification.
      The extension of biomedical approach and attribution of equal importance to
      psychosocial factors have become an imperative in the improvement of treatment
      efficacy and disease control, together with humanisation of relations between
      health staff and patients. A new biopsychosocial model has been suggested, that
      takes into account all relevant determinants of health and disease and that
      supports the integration of biological, psychological and social factors in the
      assessment, prevention and treatment of diseases. It does not diminish the
      significance of biological factors, but extends a rather narrow approach. The
      biopsychosocial model served as incentive for many studies of how psychological
      and social factors influence the development, course and outcome of a disease,
      giving rise to the development of interdisciplinary field--particularly the
      fields of health psychology and psychoneuroimmunology. Their contribution to
      better understanding of the impact of psychosocial factors on health stimulates
      greater interest of medical theory and practice in more holistic approach to a
      patient. However, the changes of the old, organ oriented approach are still too
      slow and too narrow.

PMID- 19408643
TI  - PHACES syndrome--case report and literature review.
AB  - The case of a 2-month-old female infant with PHACES syndrome is reported. PHACES
      represents a broad spectrum of congenital anomalies, including the following
      primary features: posterior fossa brain malformations, large facial hemangiomas,
      arterial anomalies, cardiac defects and aortic coarctation, eye abnormalities,
      and ventral developmental defects. The literature on this rare condition is
      reviewed.

PMID- 19408644
TI  - Giant basal cell carcinoma of the back: a case report and review of the
      literature.
AB  - Basal cell carcinoma (BCC) is the most common cutaneous malignancy and the most
      common human malignancy in general. Out of all basal cell carcinomas, giant basal
      cell carcinoma represents less than 1%. Only 10% of all basal cell carcinomas are
      located on the trunk and majority is located on the head and neck. We describe a
      patient with a exophytic giant basal cell carcinoma of the back size 8.5 x 8 x 6
      cm, infiltrating skin 1.5 cm. Two years after the lesion has occurred, diagnosis
      was made by pathohistological analysis. The patent was treated surgically, by
      excision. Review of the literature that refers to giant basal cell carcinoma was
      carried out.

PMID- 19408645
TI  - Limb salvage surgery in Enneking's stage III a--a case of leiomyosarcoma.
AB  - Limb saving surgery is today's tendency in treating the musculoskeletal tumours.
      Preserving the limb should not only pursue a good oncological and functional
      result but also aim at good psychological outcome. Our aim was to treat a very
      rare case of proximal femoral leiomyosarcoma with present solitary lung
      metastasis by conservative operative procedures.

PMID- 19408646
TI  - Trigeminal neuralgia secondary to meningioma of petroclival localization.
AB  - Trigeminal neuralgia is characterized by paroxysmal episodes of facial pain in
      the distribution of the trigeminal nerve. It can occur in either sex but is most
      frequently seen in women aged 50-60 years. This article presents case of
      trigeminal neuralgia in a 55-year-old female patient caused by meningioma of
      petroclival localization. The article underscores the importance of neurologic
      and neuroradiologic examination in diagnosing and managing patients with facial
      pain conditions.

PMID- 19408647
TI  - Paget's disease in contralateral breast occuring 11 years after mastectomy for
      invasive ductal carcinoma.
AB  - Paget's disease of the breast is a rare form of breast cancer and represents only
      1% to 4% of all breast cancers. It is characterized by the presence of Paget's
      cells in the epithelium tissue (in epidermis) and it manifests as a lesion of the
      nipple. In most cases, Paget's disease is associated with an underlying breast
      malignancy. Mastectomy has been considered the treatment of choice, but breast
      conservation is also being explored, in properly selected patients, depending on
      the underlying malignancy. We report a case of Paget's disease occurring in the
      contralateral breast 11 years after mastectomy for invasive ductal carcinoma but
      with no underlying breast malignancy.

PMID- 19408648
TI  - Pulmonary hypertension in patient with elevated homocystein level and blast
      injuries.
AB  - 38-year-old man had chronic deep venous thrombosis (DVT) as a result of multiple
      injuries caused by an explosion of grenade 12 years ago, with recurrent pulmonary
      thromboembolisms and pulmonary hypertension which was unrecognized for a decade.
      Patient was admitted with a progressive dyspnea and exercise intolerance (NYHA
      II). The diagnosis was established according to clinical symptoms, transthoracic
      echocardiography, phlebography, lung scintigraphy and pulmonary angiography. Oral
      anticoagulant therapy was introduced and cava filter indicated to implant. During
      phlebography a floating thrombus was found in the inferior cava vein underneath
      renal vein. Implantation was delayed and patient received systemic fibrinolytic
      therapy with streptokinase (7500 000 UI within 4 days), followed by heparin
      infusion and warfarin. Post-fibrinolytic phlebography showed clear lumen of
      inferior vena cava. Fibrinolysis had also affected pulmonary hypertension
      systolic pressure in the right ventricle measured by Doppler echocardiography
      decreased from 90 to 65 mmHg. Permanent intravenous cava filter was implanted.

PMID- 19408649
TI  - [Establishment of a murine model of Alternaria alternate induced allergic
      asthma].
AB  - OBJECTIVE: To develop a method of establishment of airway allergic inflammation
      model of C57BL/6 mice sensitized and challenged with the spores of Alternaria
      alternate. METHODS: C57BL/6 mice were divided into negative control group,
      positive control group and model group, twelve mice in each group. Mice of model
      group were sensitized with spores at day 0, 5, 10 by intraperitoneal injection,
      and challenged four times by intranasal drip from day 14 to day 17. OVA instead
      of spores were used in the positive control group, PBS used in the negative
      control group. Bronchoalveolar lavage fluid (BALF) was taken at 24h after the
      last time of challenge, and the pathological manifestation of the lung, cell
      counts and differential count and IL-4, IFN-gamma total protein levels in BALF
      were assessed. The levels of total IgE and specific IgE in plasma were
      identified, the airway resistance and lung compliance were determined. RESULTS:
      There was pulmonary eosinophilic inflammation in the positive control group and
      model group. Total cells count, differential cells count and IL-4 and total
      protein levels in BALF were enhanced significantly while IFN-gamma declined
      remarkably. The levels of total IgE and specific IgE were increased remarkably in
      plasma in positive control group and model group, the airway resistance was
      enhanced and lung compliance decreased. CONCLUSION: An airway allergic
      inflammation model of C57BL/6 mice has been established by sensitizing and
      challenge with spores of Alternaria alternate.

PMID- 19408650
TI  - [Acute cytotoxicity of alternariol on NIH/3T3 cells].
AB  - OBJECTIVE: To study the cytotoxicity of altemariol (AOH) on NIH/3T3 cells.
      METHODS: Logarithmic growth phase NIH/3T3 cells were treated at the dose of 10
      micromol/L and 50 micromol/L AOH as treatment groups and treated with DMSO
      (0.25%). The effects of AOH on cell proliferations were assessed by morphologic
      observasion. Inhibition rates of AOH were determined by MTT assay. Comet assay
      was used to examine DNA damage induced by AOH. Cell cycle distributions were
      detected by flow cytometric assay (FCM). RESULTS: The cells treated with AOH
      occured morlogic changes. The inhibition rates of 10 micromol/L and 50 micromol/L
      AOH were 19.88% and 32.47% respectively. In the comet assay two treatment groups
      percentages of tailed cells were 35.87% and 71.83% respectively. The DNA contents
      of the tail were (36.18 +/- 18.6) and (51.3 +/- 21.6) respectively. These datas
      were more higher than those of the solvent control (P < 0.05). In comparison with
      the control group, the percents of G2/M and S phase cells were increased after
      treatment of 50.0 micromol/L AOH for 24h (P < 0.05). CONCLUSION: AOH could have
      acute cytotoxic effects on NIH/3T3 cells and inhibite cell proliferation and
      cause DNA damage. High dose of AOH could induce cell cycle arrest in G2/M phase.

PMID- 19408651
TI  - [Inhibition of pSmad implicated in cleft palate induced by all-trans retinoic
      acid].
AB  - OBJECTIVE: To investigate the effects of excessive all-trans retinoic acid (atRA)
      on palatogenesis in mouse fetuses and level of Smad2 phophorylation (pSmad2).
      METHODS: atRA (80 mg/kg x d) was orally given to mice on embryonic day 11 (E11).
      Palatal fusion was examined by Hemagglutinin Esterase (HE). The level of Smad2
      phophorylation (pSmad2) in medial edge epithelial (MEE) was detected by
      immunohistochemistry and Western Blot, respectively. RESULTS: The incidence of
      cleft palate (CP) was 90% of total fetus in atRA-treated group. Compared with
      vehicle control group, no pSmad2 was identified in MEE in atRA-treated palatal
      shelves, which was correlated with the persistence of the MEE and failure of
      palatal fusion. CONCLUSION: Inhibition of Smad phosphorylation might be involved
      in cleft palate induced by atRA.

PMID- 19408652
TI  - [Study on the replicative and premature senescence induced by hydrogen peroxide
      of human embryonic lung fibroblasts].
AB  - OBJECTIVE: To study both cellular replicative and prematuce senescence induced by
      hydrogen peroxide (H2O2) of human embryonic lung fibroblasts (HEFs). METHODS:
      HEFs were cultured conventionally and treated with H2O2. Biomarkers of senescence
      were assessed, including cell morphology, growth curve, life span, distribution
      of cell cycle and senescence associated beta-galactosidase (SA-beta-gal), and the
      expression of proliferating cell nuclear antigen (PCNA). RESULTS: HEFs entered
      replicative senescence status at 52 population doubling levels (PDL) and 400
      micromol/L H2O2 induced premature senescence of HEFs in a short period. Senescent
      cells were characterized as enlarged, flattened and reduced saturation density,
      retarded in the G1 phase with increased expression of SA-beta-gal. The mRNA and
      protein level of PCNA decreased gradually during cellular senescence. CONCLUSION:
      Cellular premature senescence could be induced by 400 micromol/L H2O2. Premature
      senescence induced by H2O2 could share the morphology characteristics and
      proliferative capacity similar to those of replicative one.

PMID- 19408653
TI  - [Changes of the life span and certain biochemical indexes on Drosophila
      melanogaster by ethanol exposure].
AB  - OBJECTIVE: To explore the effect of ethanol on the life span and the activities
      of SOD and GSH-Px as well as the contents of MBA in Drosophila melanogaster.
      METHODS: Newly trapped and not mated 7200 flies were collected within 8 hours and
      separated by sex. 2400 flies were selected and randomly divided into six groups
      (0, 9, 27, 90, 270 and 8l0 mmol/L). Each group contained 400 flies, 200 male
      flies and 200 female flies. The numbers of dead flies were counted everyday and
      the culture mediums were replaced every 4 days until all flies died. Another 4800
      flies were randomly divided into 4 groups (0, 27, 90 and 270 mmol/L). Each group
      contained 1200 flies, half male and half female. The activities of SOD and GSH-Px
      as well as the contents of MBA were detected at the days of 0th, 10th, 20th and
      30th after ethanol exposure. Results The life span of Drosophila exposed to high
      dose ethanol reduced obviously. Activities of SOD and GSH-Px and contents of MDA
      of Drosophila exposed to ethanol reduced and enhanced with increasing of ethanol
      doses. And at the same doses (90 mmol/L and 270 mmol/L), activities of SOD and
      GSH-Px reduced, while contents of MDA elevated with increasing of exposure time.
      Exposed to high dose of ethanol at the days of 20 or 30, activities of SOD and
      GSH-Px and contents of MDA in Drosophila reduced and enhanced significantly in
      comparison with control group. CONCLUSION: Ethanol could reduce the life span and
      the activities of SOD and GSH-Px, and enhance MBA content of Drosophila.

PMID- 19408654
TI  - [Oxidative damage effects of A549 and A549-R cells induced by mainstream smoke].
AB  - OBJECTIVE: To explore the effects of oxidative damage induced by mainstream smoke
      (MS) on A549 and A549-R cells of hOGG1 deficient cell. METHODS: A549 cells and
      A549-R cells with down-regulated hOGG1 gene were treated at the concentrations of
      MS for 2h. The cellular sensitivities and DNA damages were measured by MTT assay
      and comet assay, respectively. The contents of ROS and 8-OHdG in both cells were
      examined by fluorescence method and HPLC-ECD. RESULTS: The cell viabilities
      decreased with increases of concentration of MS. The IC50 of hOGG1 deficient A549
      R cell was more lower than that in A549 cell (P < 0.05). With dose increases of
      MS, the contents of ROS increased in both cell lines. When MS was more than or
      equal to 1.25 No. of cigarette/L, the contents of ROS in A549-R cells were much
      higher than those in A549 cells. The comet assay indicated that DNA damages of
      A549-R cells were more higher than those in A549 cells, and comet rate, tail
      length and OTM in A549-R cells were more higher in comparison with A549 cells (P
      < 0.05) at the levers of all concentrations. Furthermore, the levels of 8-OHdG in
      A549-R cells were higher than those of A549 cells at the doses of 2.5 and 5 No.
      of cigarette/L (P < 0.05). CONCLUSION: Mainstream smoke could induce oxidative
      damage in A549 and A549-R cells and hOGG1 deficiency cell could increase
      sensitivity to MS.

PMID- 19408655
TI  - [Establishment of in-vitro mouse preantral follicle culture systems].
AB  - OBJECTIVE: To develop mouse preantral follicle culture for toxicology study.
      METHODS: The ovaries were from prepubertal mice (C57B1/6JxCBA/Ca) (at the ages of
      12-14 days). The ovaries were from prepubertal mice (C57B1/6JxCBA/Ca) (at the
      ages of 12-14 days). The preantral follicles with a diameter around the range 100
      130 microm were mechanically dissected and randomly allocated to 96-well plates.
      After subsequently cultured individually for 12 days, the follicles were induced
      ovulation. The in-vitro developmental characteristics of the follicles were
      observed including hormonogenesis, folliculogenesis and oogenesis 16h later after
      ovulation. In-vitro growth and maturation of oocytes (IVG) were compared with in
      vivo growth and in-vitro maturation of oocytes (IVM) to assess the in-vitro
      assay. RESULTS: 89.74% (376/419) of follicles were visibly associated with theca
      cells and possessed a close follicle (granulosa) cell/oocyte apposition. At 12
      days of culture, the average diameter of follicles were increased, the survival
      rate of follicles is 96.81% (364/376), 48.94% (184/376) of the cultured follicles
      reached the pre-ovulatory stage with a large antrum-like cavity, and 56.38%
      (212/376) COCs were released by maturation induction in this study. From
      preantral follicle to oocyte maturation and the formation of first polar body,
      the morphological observation showed that developmental characteristics of mouse
      preantral follicles in-vitro were similar to those in-vivo. The patterns of
      hormone secretion observed in preantral follicle culture were similar to the
      characteristics of in-vivo follicle hormone secretion. The numbers of oocytes
      with germinal vesicle (GV) did not differ between IVG and IVM groups, 18.89%
      oocytes form the first polar body in IVG groups and 53.53% oocytes form the first
      polar body in IVM groups. No abnormal chromosome segregation found in this study.
      CONCLUSION: This study successfully developed in-vitro mouse pre-antral follicle
      culture system, which could be a efficient tool to study folliculogenesis
      physiology and toxicology system, which could be a efficient tool to study
      folliculogenesis physiology and toxicology.

PMID- 19408657
TI  - [Study on PPARgamma and aP2 mRNA expression of adipose tissues in obesity and
      obesity resistant rats].
AB  - OBJECTIVE: To observe the difference of serum triglyceride, total cholesterol
      levels and expression of PPARgamma and aP2 mRNA of adipose tissues between
      obesity and obesity resistant rats induced by high-fat diet. METHODS: Thirty-one
      healthy male Wistar rats were randomly divided into two groups. Seven of them
      were fed with standard diet as control group and 24 rats were fed with high-fat
      diet as high-fat group. At the end of the 8th week, according to the body weight
      increment, five rats were selected as obesity group, and five rats were selected
      as obesity resistant group from high-fat feeding rats. Serum triglyceride, total
      cholesterol, and the expressions of PPARgamma and aP2 mRNA of epididymal adipose
      tissues were detected. RESULTS: Serum triglyceride of obesity group were higher
      than those of control (P < 0.05). Total cholesterol levels of obesity group were
      higher than those of control and obesity resistant group (P < 0.05, P < 0.01).
      The expressions of PPARgamma and aP2 mRNA of obesity group were also much higher
      than those of control and obesity resistant group. CONCLUSION: The expressions of
      PPARgamma and aP2 mRNA of obesity and obesity resistant rats induced by high-fat
      diet existed difference.

PMID- 19408656
TI  - [Effect of rat recombinant leptin on expression of SOCS-3 in mature adipocytes].
AB  - OBJECTIVE: To study the effect of rat recombinant leptin on expressions of
      suppressor of cytokine signaling 3 (SOCS-3) mRNA and protein in mature adipocytes
      . METHODS: Mature adipocytes were separated from epididymal adipose tissues of
      male SD rats, and the expressions of long-form leptin receptor mRNA were
      detected. The separated adipocytes were then treated with rat recombinant leptin
      at the doses of 0.5-500 nmol/L for 0.5 to 6h. The expressions of SOCS-3 mRNA were
      measured with RT-PCR and proteins were measured with immuniprecipitation combined
      with Western blot analysis. RESULTS: Low-level expressions of long-form leptin
      receptor mRNA could be measured in mature adipocytes. The adipocytes expressed
      small amounts of SOCS-3 mRNA and protein witbout leptin treatment, and no
      significant changes were observed at 0.5 Snmol/L of leptin. However, tbe
      expressions of SOCS-3 mRNA and protein increased significantly at the doses of 5
      500 nmol/L of leptin in the consistent with treatment time. CONCLUSION: Leptin
      could have direct effects on adipocytes. High leptin concentration could induce
      the expressions of SOCS-3 mRNA and protein in mature adipocytes.

PMID- 19408658
TI  - [Study on bioavailability of Fe-riched wheat varieties using an in vitro
      digestion/Caco-2 cell model].
AB  - OBJECTIVE: To select the most promising Fe-riched wheat varieties by studying Fe
      bioavailability from several wheat variety flours so as to provide scientific
      evidence for further human trials and nutrition target in wheat breeding.
      METHODS: The Fe bioavailability among 10 Fe-riched wheat flours was assessed
      using an in vitro/Caco-2 cell culture model. Caco-2 cell ferritin formation was
      measured as an indicator of Fe utilized by human Caco-2 exposing to tested flour
      digests. RESULTS: Significant differences were detected in Fe bioavailability
      among 10 flour varieties, Zhongyou 9507 (from Anyang) and Jingdong 8 with 78%
      flour yield had the highest Fe bioavailability. CONCLUSION: The two most
      promising varieties, Zhongyou 9507 (from Anyang) and Jingdong 8 will be further
      evaluated in human trials to determine their efficacy.

PMID- 19408659
TI  - [Effects of soy bean isoflavone on inhibition of benign prostatic hyperplasia and
      the expressions of NO and NOS of rats].
AB  - OBJECTIVE: To explore the inhibitive effect of soybean isoflavone on the
      prostatic hyperplasia on the expressions of nitric oxid and nitric oxide synthase
      in the prostatic hyperplasia rats. METHODS: Subcutaneously injected testosterone
      propionate were to induce prostate hyperplasia in rats. The changes of prostate
      wet weight, prostatic index, liver index, the changes of some biochemical indexes
      in rat prostate tissue in the control and the treatment, the low, moderate, high
      dose groups of soybean isoflavone groups were observed. RESULTS: The prostate wet
      weight and prostatic index in all dose groups were merely lower than those in the
      treatment and the moderate groups were lowest in all dose group. There were no
      significant differences in liver index, urea nitrogen, glutamic-pyruvic
      transaminase of each group. Acid phosphatase, prostatic acid phosphatase and
      lactate dehydrogenase in all dose groups were merely lower than those in the
      treatment group. Nitric oxide and nitric oxide synthase in all dose groups were
      merely higher than those in the treatment group. CONCLUSION: Soybean isoflavone
      could inhibit prostate hyperplasia and increase the expressions of nitric oxide
      and nitric oxide synthase in rats.

PMID- 19408660
TI  - [Effects of dietary different ratios of n-3 to n-6 polyunsaturated fatty acids
      influence lipid metabolism and appetite of rats].
AB  - OBJECTIVE: To study the effects of dietary different ratios of n-3 to n-6
      polyunsaturated fatty acids on food intake of SD rats and potential mechanisms.
      METHODS: According to their serum total cholesterol level, male rats were
      randomly divided into 6 groups, and were fed common feed diet, high fat diet,
      high fat with n-3/n-6 1:1 PUFA diet, high fat with n-3/n-6 1:5 PUFA diet, common
      feed with n-3/n-6 1:1 PUFA diet, and common feed with n-3/n-6 1:5 PUFA diet,
      respectively. Weights were measured about every 6 days, and food intake were
      measured everyday. At 0, 15, 30 and 45 days, triglycerides (TG) and total
      cholesterol (TC) in the plasma were measured using kits. After 45 days, the rats
      were sacrificed. RT-PCR was used for measuring the expression of neuropepide Y
      (NPY) and AMP-activated protein kinase-alpha2 (AMPK-alpha2) mRNA in the
      hypothalamus. RESULTS: Four diets with any ratio of n-3/n-6 PUFA resulted in
      significant restraint of body weight gain, TC and TG level in the plasma, NPY and
      AMPK-alpha2 mRNA level in the hypothalamus compared to high fat diets (P < 0.05).
      These situations in two groups with common diet and one group with high diet
      added 1:1 PUFA are more significant than the high fat diet group. CONCLUSION:
      These results indicate that dietary PUFA improved lipid metabolism which may be
      related with appetite control through AMPK path.

PMID- 19408661
TI  - [Effect of dietary genistein on rats development exposure after their weaning].
AB  - OBJECTIVE: To investigate the effects of dietary genistein on the development of
      young rats. METHODS: SD rats aged three-week were randomly divided into three
      groups according to their weight (eight male and eight female). Each group was
      fed a diet containing genistein at levels of 0, 20 and 100 mg/kg. Several
      development indices were observed each week. At the age of 9 weeks, blood samples
      were collected and the plasma estradiol level of female rats and plasma
      testosterone level of male pups were measured. At the age of 13 weeks, organs(
      ovary and uterns in female, testes in male) were examined for histopathological
      changes and the expression of the estrogen receptor was measured by Western
      blotting. RESULTS: The plasma estradiol level of female rats increased and the
      plasma testosterone level of male rats decreased at the age of 9 weeks compared
      to the control group. At the age of 13 weeks, decreased body weight, food
      consumption, anogenital distance (AGD) and overy weight in female rats were
      observed. Also, the vaginal open time of female pups was earlier than control
      group. Histopathology showed that the cavity of uterus was larger than control
      group. Otherwise, treatment with genistein caused reduction in the plasma
      estradiol level of female rats and the expression of estrogen receptor-alpha in
      uterus. There were few changes of male rats' body weight, testicular descent,
      testes weight and histopathology except that the increased food consumption from
      10-week-old and plasma testosterone level. CONCLUSION: Genistein exposure could
      effect on both sexes of young rats' development. The effects on female rats were
      much more than that on male rats and the effect of rats body weight and food
      consumption was mainly after their growing up. Although the mechanism of these
      effects are still obscure, it seems that the change of hormone level and
      expression of estrogen receptor have some relation with these effects.

PMID- 19408662
TI  - [Experimental study for the anti-fatigue effect of ginseng general ginsenosides
      P.E. in vivo].
AB  - OBJECTIVE: To investigate the effective dose and the possible mechanism of the
      anti-fatigue effect of ginsenosides and then deduce to the recommended intake of
      human body. METHODS: Healthy adult male SD rats intook ginsenosides solution
      every day through stomach at doses of 50, 150, 250 mg/kg per day, other rats were
      divided into untreated group and model control group, given equal amount of
      distilled water for 30 days. Conducted exhaustive swimming experiment for rats
      except untreated group on the last day of gavage after 30 minutes. Determine the
      time of the exhaustive swimming, organ coefficient, liver glycogen, muscle
      glycogen, malonaldehyde (MDA) of liver cells, superoxide dismutase (SOD) of liver
      cells, Na+ -K+ adenosine triphosphatase (Na+ -K+-ATPase) and Ca2+ -Mg2+ adenosine
      triphosphatase (Ca2+ -Mg2+-ATPase) of erythrocyte, blood lactate, fumaric
      reductase. RESULTS: The body weight of rats middle, high dose group were higher
      than that in model control group after exhaustive swimming (P < 0.05). The time
      of the exhaustive swimming of high dose group were longer than model control
      group (P < 0.05). Some organ coefficient of model control group have
      statistically significant compared with other groups (such as brain, kidney,
      adrenal, thymus coefficient) (P < 0.05). The activity of SOD of liver cells of
      untreated group, middle dose group and high dose group were higher than model
      control group and low dose group (P < 0.05), but the level of MDA of liver cells
      of them were lower than model control group and low dose group (P < 0.01), the
      activity of Na+ -K+-ATPase of erythrocyte of untreated group and high dose group
      were higher than model control group (P < 0.05), but the activity of Ca2+ -Mg2+
      ATPase of erythrocyte of each group had no statistical significance (P > 0.05).
      The level of liver glycogen, muscle glycogen and fumaric reductase of model
      control group were lower than untreated group and high dose group (P < 0.05).
      CONCLUSION: At the experimental conditions, ginsenosides solution of 250 mg/kg
      can improve the tolerance of rats in fatigue campaign and have the function of
      anti-fatigue.

PMID- 19408663
TI  - [Analysis of phytosterol contents in food plant materials and Chinese traditional
      medicines].
AB  - OBJECTIVE: To analyze the phytosterol content in food plant materials and Chinese
      traditional herbal medicines commonly used in China. METHODS: 18 kinds of food
      plant materials and 32 kinds of Chinese traditional herbal medicines, which were
      commonly used in functional food, were chosen as samples. The contents of beta
      sitosterol, campesterol, stigmasterol, beta-sitostanol were analyzed by GC
      methods and the percent of each ingredient were calculated. RESULTS: The contents
      of phytosterols in 18 kinds of food plant materials were from 14.8 mg/100 g to
      208.3 mg/100 g, while the content of phytosterols in 32 Chinese traditional
      herbal medicines were from 9.4 mg/100 g to 280.3 mg/100 g. In most samples, beta
      sitosterol is the largest part of total phytosterol. CONCLUSION: Phytosterols
      were existed in 50 kinds of food plant materials and Chinese traditional herbal
      medicines commonly used in functional food, maybe phytosterol is an important
      functional ingredient in some plant materials.

PMID- 19408664
TI  - [Effects of calcium and vitamin D supplementation on bone specific alkaline
      during pregnancy lactation and infant].
AB  - OBJECTIVE: To investigate the effect of calcium and vitamin D supplementation
      during pregnancy, lactation and infants on bone development of infant. METHODS:
      1176 health infants aged 42-365 days and their mothers were recruited as subjects
      at Pediatric Department in Beijing Obstetrics and Gynecology Hospital during
      November 2006 to January 2008. Retrospective questionnaire was asked about
      calcium and vitamin D supplementation during pregnancy, lactation and infant.
      Blood bone-specific alkaline (BAD) and fontanel anterior (FA) of infant were
      measured. Chi2 test and logistic regression were used to analyze the research
      data. RESULTS: The chi2 test result showed that maternal supplementation with Ca
      and vitamin D during breastfeeding could decrease infant BAP significantly (P =
      0.018), while supplementation during pregnancy could not (P = 0.154). The
      logistic regression result showed that infant supplementation with Ca and Vitamin
      D could decrease infant BAP significantly (P = 0.000), while infant feeding
      methods could not (P > 0.05). The FA size of infants aged < or =42 days had
      significant negative relationship with BAP (P = 0.017), and no relationship with
      Ca and vitmin D supplementation during pregnancy. CONCLUSION: Supplementation
      with Ca and vitamin D of mother during lactation and infant could significantly
      decrease infant BAD. The FA size could not indicate the infant calcium status.

PMID- 19408665
TI  - [Impacts of self-management on glycaemic control among type 2 diabetic
      outpatients in urban China].
AB  - OBJECTIVE: To explore the influences of patients' self-management to glycaemic
      control among type 2 diabetic mellitus (T2DM) outpatients in urban China.
      METHODS: A cross-sectional study was carried out in 1524 T2DM outpatients from 15
      hospitals in 4 major cities of China. Questionnaire interview was used by trained
      surveyors to collect data on general characters and self-management. HbA1c test
      was applied to measure blood glucose in the centralized hospital in each city.
      Logistic regression was used to examine the association between self-management
      components including diet control, knowledge,blood monitoring and regular
      exercises and level of HbA1c. RESULTS: 1524 outpatients were enrolled in the
      study. Multivariate analysis showed that patients who were under diet control (OR
      = 0.49, 95% CI: 0.34 - 0.72), knowledgeable on DM (OR = 0.60, 95% CI: 0.46 -
      0.80), compliance behavior (OR = 0.63, 95% CI: 0.40-0.98), having regular
      monitoring on blood glucose (< or = 4 times/month: OR = 0.66, 95% CI: 0.50 -
      0.87; > 4 times/month: OR = 0.51, 95% CI: 0.36 - 0.73) and examining HbA1c (< or
      = 3 times per year: OR = 0.33, 95% CI: 0.23 - 0.48; 0-3 times per year: OR =
      0.57, 95% CI: 0.43 - 0.74) were more likely to have a better glycaemic control
      measured by HbA1c. CONCLUSION: Diet control, knowing diabetes, compliance
      behavior and regular monitoring on blood glucose and examining HbA1c can improve
      the glycaemic control among T2DM outpatients in urban China.

PMID- 19408666
TI  - [Study on the vitamin a nutrition status in plasma of children at the ages of 3
      12 years in different Chinese rural areas].
AB  - OBJECTIVE: To know the Vitamin A nutrition status of children at the ages of 3-12
      years in different Chinese rural areas. METHODS: Blood samples were drown from 88
      investigated counties of National Nutrition and Health Survey 2002,while each age
      group of children from boys and girls 6 blood samples were drown respectively.
      All blood samples were determined with HPLC. RESULTS: In coastal,interior and
      western area,the vitamin A deficiencies of at the ages of 3-12 years children
      were 5.5%, 15.4%, 10.2%, and the marginal vitamin A deficiencies were 40.5%,
      53.8%, 50.1%. The vitamin A deficiencies and the marginal vitamin A deficiencies
      in coastal area could be lower than in interior and western area. CONCLUSION: The
      vitamin A nutrition status is related with the geographic, food intake and life
      style.

PMID- 19408667
TI  - [Study on the determination method of the astragaloside IV in health food].
AB  - OBJECTIVE: To built an analytical methods to test Astragaloside NV in health
      food. METHODS: The reaction conditions of ultrasonic extraction, liquid-liquid
      extraction, macroporousresin column chromatography, solid-phase extraction,
      derivatization and HPLC method were analyzed. RESULTS: The sample preparations
      were set up as followed: The samples were extracted with methanol. The extraction
      solutions were liquid-liquid extracted by ether, water-saturation n-butyl alcohol
      and 1% KOH. The extraction solutions were further purified by DM-301
      macroporousresin column chromatography and Oasis HLB 3cc extraction catridge in
      turn. The purified solutions were derived with chloroform and benzoyl chloride.
      The linear ranges were 3.84 - 153.60 microg/ml. The detection limits were 2.13
      microg/ml. The recoveries were 74.85% - 91.83%. CONCLUSION: The method was
      applied to detect the concentration of Astragaloside IV in health food. It was
      enough to wipe out impurity of samples. Detection limit and recycle ratio were
      satisfied.

PMID- 19408668
TI  - [Effect of konjac polysaccharide on levels of leptin and Na+ -K+-ATPase of mice
      treated with high fat].
AB  - OBJECTIVE: To investigate the effect of konjac polysaccharide on serum leptin and
      intestinal mucosa Na+ -K+-ATPase activity of mice treated with high fat. METHODS:
      Mice were divided into normal control, high-fat control, and high, middle, low
      dose of konjac polysaccharide combining high fat groups. The mice were feed for
      twenty days. The levels of serum leptin were determined by ELISA method, and
      intestinal mucosa Na+ -K+-ATPase activities were determined by spectrophotometry.
      The body weight, adipose tissue and blood glucose were also examined. RESULTS: At
      the 10th day, body weight and postprandial blood glucose of high-fat control
      group were (31.3 +/- 2.11) g and (7.5 +/- 1.15) mmol/L, those of high dose konjac
      polysaccharide combining high fat group were(28.0 +/- 2.06) g and (4.8 +/- 0.73)
      mmol/L. At the 20th day, concentrations of serum leptin and Na+ -K-ATPase
      activities of high-fat control group were (1078.5 +/- 61.69) pg/ml and (16.2 +/-
      1.48) micromol Pi/(mg pro x h), those of high dose konjac polysaccharide
      combining high fat group were (820.5 +/- 58.52) pg/ml and (11.2 +/- 1.10)
      micromol Pi/(mg pro x h). All differences between two groups were significant (P
      < 0.05). CONCLUSION: Konjac polysaccharide could decrease level of body weight,
      postprandial blood glucose, serum leptin and intestinal mucosa Na -K+-ATPase
      activity of mice treated with high fat.

PMID- 19408669
TI  - [Determination of acephate in air of workplace].
AB  - OBJECTIVE: To establish a standard gas chromatographic method for determinating
      acephate in air of workplace. METHODS: Acephate in the air was collected with
      polyurethane foamed plastics, desorbed with methanol, separated and determined by
      capillary GC column. RESULTS: The penetrant capacity of polyurethane foamed
      plastics tube was more than 2.4 mg, the desorption efficiency was above 90%, the
      recoveries of diazepam were 95.4% - 100.5%, the relative standard deviation
      varied from 5.1% - 7.4%, the detection limit was 0.31 microg/ml. CONCLUSION: The
      method is suitable for the determination of acephate in the air of workplace.

PMID- 19408670
TI  - [Balb/c 3T3 cell transformation assay and its application to the screening of
      carcinogens].
AB  - A cell transformation assay may be an in vitro assay measuring the phenotypic
      conversion from normal to malignant characteristics in Balb/c 3T3 cells exposed
      to test chemicals, and capable of detecting carcinogens. In this article, the
      progress and improvement of Balb/c 3T3 cells transformation assay, and its
      applications in the detection of tumor initiator and promoter were reviewed.

PMID- 19408671
TI  - [Relationship of single nucleotide polymorphism, environmental factors and the
      hereditary susceptibility of hepatocellular carcinoma].
AB  - Resulting by the interaction between the hereditary factor and the environmental
      factor, the occurrence and development of hepatocellular carcinoma (HCC) is a
      complicated course with multi-genes and multi-factors. As the third genetic
      marker, the single nucleotide polymorphism reflects the hereditary difference
      among individuals, decides the susceptibility to disease and becomes an important
      tool to study the hereditary susceptibility of HCC.

PMID- 19408672
TI  - [Research progress of pharmaceutical and personal care products on ecological and
      human health].
AB  - EU (European Union) and Center of Water Pollution and Control in the United
      States have continued to measure persistent bioaccumulate and toxic (PB&T)
      chemicals and persistent organic pollutants (POPs) since the 1970s. In resent
      years, Pharmaceutical and personal care products (PPCPs) have raised more concern
      among chemists and toxicologists. The present paper introduced the main
      properties of PPCPs and their present situation of research. Additionally, the
      potential toxicites of PPCPs to ecological and human health were detailedly
      reviewed in this article.

PMID- 19408673
TI  - [Study advance on formation, transformation and detection of masked
      deoxynivalenol].
AB  - Conjugated deoxynivalenol, in which the toxins were usually bound to a more polar
      substance like glucose in crops, is referred to as masked deoxynivalenol. It
      could not detected with routine detection methods, but could release its toxic
      precursor after hydrolysis in gastrointestinal tract. In this paper, summarizes
      the formation, transformation and detection of masked deoxynivalenol as well as
      its relationship with human health were reviewed.

PMID- 19408674
TI  - [Cooperation study of health eating index and china diet balance index].
AB  - The evaluation methods of Both health eating index (HEI) and China diet balance
      index (DBI) were established based on dietary guidelines of diet quality. The
      characteristics of HEI and DBI were reviewed from several aspects of
      establishment foundation and development, scoring system and methods,
      application, advantages and disadvantages.

PMID- 19408675
TI  - [Viable but nonculturable state of bacteria and its hygiene significance].
AB  - Viable but nonculturable state of bacteria means the state of bacteria cannot be
      cultured in routine media, but is alive and metabolic active. Many bacteria
      including some pathogens can enter this state and maintain virulence or
      pathogenicity. In this paper, the information including character, induction
      factors, resuscitation, detection and hygiene significance about bacteria's
      viable but nonculturable state was reviewed.

PMID- 19408676
TI  - [Recent advances in the structure-activity relationship study of small-molecule
      sodium channel blockers with analgesic effects].
AB  - Pain is one of the common clinical symptom, previous studies have implicated
      sodium channels as a key constituent in pain signaling. Sodium channel blockers
      with efficient sodium channel blockade effect play an important role in analgesic
      treatment. However, most drugs used in clinic have many drawbacks and can not
      meet the demand of the clinical use. Therefore, for the development of new
      generation of sodium channel blockers, it is of great significance to find small
      molecule sodium channel blocking lead compounds with novel chemical scaffolds and
      new structures, sodium channel blocking activity and structure-activity
      relationship are discussed in detail, and current problems and trends in future
      research are also emphasized.

PMID- 19408677
TI  - [Folate receptor-mediated antitumor drugs].
AB  - Folate receptor (FR) is over-expressed in a variety of human cancers and it is
      seldom expressed or found in normal tissues. Therefore, folate receptor-mediated
      antitumor drugs can be targeted specially to the FR-positive tumor cells. This
      strategy improves the selectivity of drugs which may destroy the normal tissues
      in traditional chemotherapeutics. This review provides the delivery mechanism of
      FR-mediated antitumor drugs and highlights the novel folate-drug conjugates and
      their activities.

PMID- 19408678
TI  - [The effect of chelerythrine on the hypertrophy of cardiac myocytes of neonatal
      rats induced by different glucose levels and its mechanism].
AB  - The purpose of this study is to investigate the effect of chelerythrine on the
      hypertrophy of cardiomyocytes of neonatal rats induced by different glucose
      levels and its mechanism. Using cultured neonatal ventricular myocytes as a
      model, groups were divided as: control (5 mmol x L(-1)); high glucose level (10,
      15, 20, and 25.5 mmol x L(-1)); high glucose level (25.5 mmol x L(-1)) add
      different concentrations of chelerythrine (1 and 8 micromol x L(-1)); and control
      glucose level (5 mmol x L(-1)) add different concentrations of chelerythrine (1
      and 8 micromol x L(-1)). Different groups of cardiomyocytes after adding
      corresponding treat factors were cultured for 48 hours. Cardiomyocytes' diameters
      and protein level were measured and the expression of PKC-alpha, PKC-beta2, p-PKC
      alpha, and p-PKC-beta2 were measured by Western blotting. Compared with control
      group, neonatal myocytes cultured in high glucose levels showed increased
      cellular volumes, protein level and expression of PKC-alpha, PKC-beta2, p-PKC
      alpha, p-PKC-beta2. When chelerythrine was added, cellular volumes, protein level
      and expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2 were
      significantly reduced. But in 1 micromol x L(-1) chelerythrine group, the
      expression of PKC-beta2 was not significantly reduced. The result suggested that
      chelerythrine can reverse the hypertrophy induced by different glucose levels on
      the cardiac myocytes, it may have protective effect against diabetic
      cardiomyopathy via PKC passageway.

PMID- 19408680
TI  - [Protective effect of calcium dobesilate against early diabetic nephropathy of
      rat kidney].
AB  - The aim of this study is to study the effect of calcium dobesilate on
      streptozotocin (STZ)-induced early diabetic nephrophathy (DN) in rats. All male
      Wistar rats were randomly divided into six groups: normal group; DN blank group;
      calcium dobesilate 75, 150, and 300 mg x kg(-1) groups and perindopril 0.4 mg x
      kg(-1) group. Blood glucose and the 24 h urinary albumin were measured
      dynamically during the experiment, after 8 weeks administration, the level of
      glycosylated hemoglobin (HbA1c) was determined, the expressions of plasminogen
      activator inhibitor-1 (PAI-1) and matrix metalloprotein-9 (MMP-9) in cortex of
      kidney were examined with immunohistochemical staining. The endothelin (ET) in
      plasma and kidney cortex was measured with radioimmunoassay, renal pathomorphism
      was observed with light and electron microscopes. Calcium dobesilate could
      decrease the 24 h urinary albumin and ET in plasma and kidney cortex, down
      regulate the expression of PAI-1, and up-regulate MMP-9 in kidney. These findings
      suggested that calcium dobesilate could protect blood vessel endothelium, inhibit
      kidney fibrous degeneration, ameliorate renal pathological damage, and protect
      kidney function in many ways.

PMID- 19408679
TI  - [Effects of fluvastatin on the activation of p38 mitogen-activated protein kinase
      in glomerular mesangial cells under high concentration of glucose].
AB  - This study is to investigate the effects of fluvastatin on the activation of p38
      mitogen-activated protein kinase (p38 MAPK) and cAMP response element-binding
      protein (CREB1) in glomerular mesangial cells under high concentration of
      glucose. High concentration glucose and fluvastatin were used to stimulate the
      cultured rat glomerular mesangial cells (GMCs) in vitro. The protein expressions
      of p38 MAPK, CREB1, p-p38 MAPK and p-CREB1 were observed with Western blotting.
      TGF-beta1 and fibronectin (FN) mRNA were measured with reverse transcription and
      polymerase chain reaction (RT-PCR). The protein synthesis of laminine (LN) and
      type IV collagen in the supernatants of the GMCs were detected with
      radioimmunoassay. Compared with low glucose control group, the expressions of p
      p38 MAPK, p-CREB1 were increased obviously in high glucose group, TGF-beta1 mRNA
      and FN mRNA, LN and type IV collagen in the supernatants were increased
      significantly in GMCs under high concentration glucose medium. The expression
      levels of p-p38 MAPK, p-CREB1, TGF-beta1 mRNA, and FN mRNA, LN and type IV
      collagen in the supernatants were significantly lower in the fluvastatin group
      than those in the high concentration glucose group. It is concluded that
      fluvastatin can inhibit over production of TGF-beta1 and ECM proteins in GMCs
      under high concentration of glucose, partly by regulating the phosphorylation of
      p38 MAPK and CREB1.

PMID- 19408681
TI  - [Mechanisms of gross saponins of Tribulus terrestris via activating PKCepsilon
      against myocardial apoptosis induced by oxidative stress].
AB  - This study is to observe the effect of gross saponins of Tribulus terrestris
      (GSTT) on protein kinase Cepsilon (PKCepsilon) and apoptosis-associated protein
      in the apoptosis of cultured cardiocyte apoptosis induced by hydrogen peroxide
      (H2O2), and to explore the mechanisms of GSTT against myocardial apoptosis.
      Primary cardiocytes were isolated and cultured. Myocardial apoptosis was induced
      by H2O2 and analyzed with flow cytometry. Protein content of phospho-PKCepsilon,
      Bcl-2, and Bax were detected with Western blotting analysis. Cleaved caspase-3
      protein content was determined with immunocytochemical technique. After the
      pretreatment of 100 mg x L(-1) GSTT, compared with H2O2 group, GSTT could not
      only decrease the apoptotic percentage in cardiocytes damaged by H2O2 (P < 0.01),
      but also reduce protein contents of Bax and cleaved caspase-3 (P < 0.01), and
      increase protein content of phospho-PKCepsilon and Bcl-2 significantly (P <
      0.01). PKC inhibitor chelerythrine (Che) could prevent partly the effect of GSTT
      against myocardial apoptosis (P < 0.05 and P < 0.01). Mechanisms of GSTT against
      myocardial apoptosis might be associated with inhibition of mitochondrial
      apoptosis pathway after PKCepsilon activation.

PMID- 19408682
TI  - [Antitumor mechanism of Qinghaosu derivatives--molecular docking studies of
      Qinghaosu derivatives with transferrin].
AB  - To investigate the antitumor mechanism of artemisninin, a flexible docking
      analysis was used to score all kinds of functions of 11 Qinghaosu derivatives and
      transferrin with different resolutions. The distances of Asp-63, Tyr-188, His
      249, Arg-124 and Lys-296 with Qinghaosu were less than 0.5 nm, separately.
      Meanwhile, the higher is the activity of Qinghaosu derivatives the higher is the
      score. Our model explains that Fe2+ is more feasible to react with Qinghaosu, and
      not involved in other metabolism in presence of transferrin. Docking results
      unveil that Iron(II)-transferrin increased the cytotoxicity of Qinghaosu
      derivatives and provide a rational basis for further design and synthesis of
      novel Qinghaosu derivatives.

PMID- 19408684
TI  - [Seperation and structure elucidation of alkaloids from Chinese drug buzhaye,
      Folium Microcos].
AB  - From the chloroform extracts of the dried Folium Microcos, four compounds were
      isolated by using repeated column chromatography on silica gel and
      recrystallization and their structures were elucidated by physicochemical
      properties and UV, MS and NMR, separately. They are N-methyl-6alpha-(deca-1', 3',
      5'-trienyl)-3beta-methoxy-2beta-methylpiperidine, 6-(deca-1', 3', 5'-trienyl)-3
      methoxy-2-methylpiperidine, N-methyl-6-(deca-1', 3', 5'-trienyl)-2, 3
      dimethylpiperidine and N-methyl-6-(deca-1', 3', 5'-trienyl)-2-methylpiperidine,
      named as micropiperidine A, micropiperidine B, micropiperidine C and
      micropiperidine D, respectively. The latter three are new compounds.

PMID- 19408683
TI  - Non-nucleoside reverse transcriptase inhibitors (Part 18): synthesis and anti-HIV
      activity of 4-allylamino or 4-azido substituted diaryltriazines.
AB  - Eight new diaryltriazine derivatives containing 4-allylamino and 4-azido
      substitutes guided by molecular docking have been designed and synthesized based
      on our previous work. The evaluation of HIV inhibitory activity demonstrated that
      all compounds were potent against HIV-1 replication. The most active compound 7c
      exhibited activity against HIV-1 (IC50 = 0.034 micromol x L(-1), SI = 6,475) and
      the double mutant strain (IC50 = 9.39 micromol x L(-1)) in the micromolar range,
      which was more potent than nevirapine.

PMID- 19408685
TI  - [Xanthones from leaves of Calophyllum inophyllum Linn].
AB  - To study the xanthones from the leaves of Calophyllum inophyllum Linn., several
      chromatography methods were employed to isolate the constituents. Investigation
      on the CHCl3 extract led to the isolation of a new xanthone named inophyxanthone
      A (1) and four known compounds, which were pancixanthone A (2), gerontoxanthone B
      (3), jacareubin (4) and pyranojacareubin (5). Among them, compound 2 was obtained
      from this plant firstly, and compound 3 was obtained for the first time from this
      genus. The structure of inophyxanthone A (1) was identified as 1, 3, 5-trihydroxy
      2-(1, 1-dimethylallyl)xanthone by spectral analysis.

PMID- 19408686
TI  - [Isoflavones from Millettia nitida var. hirsutissima].
AB  - To study the chemical constituents of Millettia nitida var. hirsutissima, the
      constituents were isolated by chromatographic techniques, and structures were
      identified by spectroscopic methods. Eight isoflavones were isolated and
      identified, including a new compound, hirsutissimiside F (1), and seven known
      compounds, formononetin (2), ononin (3), odoratin 7-O-beta-D-glucopyranoside (4),
      lanceolarin (5), afromosin (6), sphaerobioside (7), and hirsutissimiside B (8).
      Compounds 3, 4, 5 and 7 were isolated from the genus Millettia for the first
      time, 2 was obtained from this plant for the first time.

PMID- 19408687
TI  - [Biological evaluation of Radix Isatidis based on neuraminidase activity assay].
AB  - Radix Isatidis (Banlangen in Chinese) is a traditional Chinese medicinal (TCM)
      herb, and is frequently used for treating influenza. However, the current quality
      control method for Radix Isatidis should be developed since it has little
      correlation to the pharmacodynamic action. In this paper, the in vitro inhibitory
      action of Radix Isatidis on neuraminidase (NA) was investigated by fluorometric
      assay with 4-methylumbelliferyl-D-N-acetylneuraminate (FL-MU-NANA) method. Based
      on the method, the experimental condition was optimized and a bioassay statistic
      method was established according to the reaction type and the regularity of
      "parallel lines of qualitative effect". Then the bioassay method of Radix
      Isatidis was established. This study indicated that Radix Isatidis had obvious in
      vitro inhibitory activity on NA with IC50 = (0.90 +/- 0.20) mg x mL(-1) (herb).
      The correlation between logarithmic dose and reaction rate showed an "S" shape-
      is quite similar to Tamiflu's reaction curve, which hinted that Radix Isatidis
      had the same inhibitory function on NA as Tamiflu. The established bioassay
      method of "parallel lines of qualitative effect" had a good reproducibility (RSD
      = 5.78%). The results of potency determination of Radix Isatidis were reliable
      (reliability test: deviation from straight line P > 0.05, deviation from parallel
      line P > 0.05) and well regular. As a conclusion, this bioassay method is
      suitable to control and evaluate the quality of Radix Isatidis.

PMID- 19408688
TI  - [Identification and analysis of absorbed components in rat plasma after oral
      administration of active fraction of Corydalis yanhusuo by LC-MS/MS].
AB  - To analyze and identify the constituents in rat plasma after oral administration
      of the active fraction of Corydalis yanhusuo, a LC-MS/MS method was established.
      The constituents absorbed into blood, their original crude drugs and their
      metabolites were identified either by comparing the retention time and mass
      spectrometry data with that of reference compounds or by mass spectrometry
      analysis and retrieving the reference literatures. Nine species are the original
      form in Corydalis yanhusuo, moreover, some metabolites in blood identified as
      glucuronide were found. The constituents absorbed into blood and the possible
      metabolites which demonstrate to originate from the active fraction of Corydalis
      yanhusuo are responsible for the observed efficacy. Its serum pharmacochemistry
      should be subjected to complete investigation so as to illuminate the
      pharmacology and active mechanism of the active fraction of Corydalis yanhusuo.

PMID- 19408689
TI  - Spectrophotometric determination of tranexamic acid using vanillin.
AB  - A new spectrophotometric method has been examined for the determination of the
      tranexamic acid (TA) by derivatization with vanillin (VAN). The molar
      absorptivity of TA was calculated 25,160 L x mol(-1) x cm(-1) at lambdamax 354 nm
      and obeyed the Beer's law within 0.5-2.5 microg x mL(-1). The color reaction was
      highly stable and did not show any change in absorbance up to 24 h. The method
      was applied for the analysis of TA from capsules, injections and tooth pastes.
      The amounts of TA found in capsules, injections and tooth pastes of various
      pharmaceutical companies were observed with 249.0-250.9 mg/capsule, 249.3-250.7
      mg/injection and 0.048%-0.049% in tooth pastes with relative standard deviation
      (RSD) 0.2%-5.0% (n = 3).

PMID- 19408691
TI  - Transport of aripiprazole across Caco-2 monolayer model.
AB  - This study aimed to investigate the transport characteristics of aripiprazole. A
      human intestinal epithelial cell model Caco-2 cell in vitro cultured had been
      applied to study the transport of aripiprazole. The effects of time,
      concentration of donor solutions, pH, temperature and P-glycoprotein inhibitor on
      the transport of aripiprazole were investigated. The determination of
      aripiprazole was performed by HPLC. It is concluded that aripiprazole is
      transported through the intestinal mucosa via a passive diffusion mechanism
      primarily, coexisting with a carrier-mediated transport. The transport of
      aripiprazole is positively correlated to transport time, pH, and temperature.
      Papp increased with donor concentrations up to 10 microg x mL(-1), and then
      decreased for higher concentrations. The P-glycoprotein inhibitor cyclosporine A
      significantly enhanced the transport amount of aripiprazole.

PMID- 19408690
TI  - [Effects of magnetic gemcitabine stealth nano-liposomes on the characteristics of
      breast cancer cell line MCF-7].
AB  - The magnetic responsibility and antitumor effect of magnetic gemcitabine stealth
      nano-liposomes (MGSL) on breast cancer cell line MCF-7 in vitro and in vivo was
      evaluated. The magnetic response and targeting effect of MGSL in vivo were
      investigated. Morphological feature and ultrastructure changes of apoptosis of
      MCF-7 cells were observed. The effect of MGSL on proliferation inhibitory rate of
      MCF-7 cells was measured with MTT method. The FCM analysis was carried out to
      examine the cell cycle distribution and cell apoptotic rate. The antitumor effect
      on human breast cancer xenografts in nude mice was also studied. MGSL was able to
      converge at the targeting tissue under tridimensional magnetic field and the
      gemcitabine concentration around it increased, while the amount of gemcitabine in
      other organs decreased, such as in kidneys and heart. MCF-7 cell line was
      sensitive to MGSL and the cytotoxity was correlated with the loaded drug dose.
      The effect of MGSL on apoptosis of MCF-7 was obvious and the rate of apoptosis
      was 51.62%. The growth speed of tumor in the group of MGSL (+) significantly
      slowed down than that of other groups. MGSL prepared by reverse-phase evaporation
      method met with the demand of targeted delivery system, and it might be an
      effective antitumor agent.

PMID- 19408693
TI  - [The effect of polyamidoamine (PAMAM) dendrimers on the solubility and
      pharmacokinetics of breviscapine].
AB  - To study the solubilization of breviscapine with polyamidoamine (PAMAM)
      dendrimers and probe the solubilizing mechanism and investigate the influence of
      PAMAM dendrimers on the pharmacokinetics of breviscapine, the solubilization of
      breviscapine by PAMAM dendrimers of generations G1, G1.5, G2 and G2.5 with
      different concentrations were determined and compared in different pH conditions.
      Twelve rats randomized into 2 groups were separately orally administered
      breviscapine and breviscapine combining with PAMAM. Drug in plasma was extracted
      and determined with HPLC. In pH condition lower than 7.0, the solubilization of
      breviscapine by PAMAM dendrimers enhanced as the generation and concentration of
      PAMAM dendrimers as well as the pH increased. Its solubilizing mechanism involves
      an electrostatic interaction between the carboxyl group of breviscapine and the
      primary amines and tertiary amines of PAMAM dendrimers. The pharmacokinetics
      parameters Cmax and AUC0-8 h of breviscapine were (119.65 +/- 9.36) ng x mL(-1)
      and (370.09 +/- 63.08) ng x h x mL(-1). For breviscapine combined with PAMAM
      dendrimers, the Cmax and AUC0-8 h were (518.17 +/- 17.07) ng x mL(-1) and
      (1,219.47 +/- 201.87) ng x h x mL(-1), respectively. There were significant
      differences of AUC0-8 h between breviscapine and breviscapine combined with PAMAM
      dendrimers (P < 0.01). PAMAM dendrimers can greatly increase the solubility of
      breviscapine in water and can improve the oral bioavailability of breviscapine
      significantly.

PMID- 19408692
TI  - [Preparation of self-assemble nobiletin proliposomes and its pharmacokinetics in
      rats].
AB  - To prepare self-assemble nobiletin proliposomes and study its pharmacokinetic
      behavior in rats after ig administration, and nobiletin suspension was used as
      control, self-assemble nobiletin proliposomes were prepared by a new proliposome
      preparation method, their physicochemical properties including encapsulation
      efficiency, particle size and stability of formed liposome were determined.
      Plasma concentration of nobiletin was determined by HPLC taking nimodipine as
      internal standard. The pharmacokinetic parameters were calculated by Kinetica 4.4
      software. The encapsulation efficiency of nobiletin liposomes was more than 80%,
      with an average particle size of 212.1 nm and very good stability. Compared to
      nobiletin suspension, nobiletin liposomes possessed higher absorptive rate and
      longer MRT, and the relative bioavailability was 264.3% in rats. It could be
      concluded that self-assemble nobiletin proliposome was a simple and feasible
      preparation, and showed greater absorption compared with nobiletin suspension.

PMID- 19408695
TI  - [Fifty years of scientific career in retrospect].

PMID- 19408696
TI  - [Modulation of Kv4 channels by KChIPs clamping].
AB  - The rapidly inactivating (A-type) potassium channels regulate membrane
      excitability that defines the fundamental mechanism of neuronal functions such as
      pain signaling. Cytosolic Kv channel-interacting proteins KChIPs co-assemble with
      Kv4 (Shal) alpha subunits to form a native complex. The specific binding of
      auxiliary KChIPs to the Kv4 N-terminus results in modulation of gating
      properties, surface expression and subunit assembly of Kv4 channels. Based on
      recent structural efforts, here we attempt to emphasize the interaction between
      KChIPs and Kv4 channel complex in which a single KChIP1 molecule laterally clamps
      two neighboring Kv4.3 N-termini in a 4:4 manner. Greater insights into molecular
      mechanism between KChIPs and Kv4 interaction may provide therapeutic potentials
      by structure-based design of chemical compounds aimed at disrupting the protein
      protein interaction for treatment of membrane excitability-related disorders.

PMID- 19408694
TI  - [Optimization of a floating osmotic pump system of dipyridamole using central
      composite design-response surface methodology].
AB  - A new type of floating osmotic pump of dipyridamole was designed in this paper.
      Apparatus three (Chinese Pharmacopeia 2005, appendix XD) was employed for in
      vitro dissolution test in order to evaluate the release and floating behavior in
      a same experiment. The system was optimized using central composite design
      response surface methodology; where similarity factor (f2) between the
      dissolution profile of prepared formulation and the target dissolution profile
      was taken as dependent factor, usage amount of polyoxyethylene (X1, mg), NaCl
      (X2, mg) and pore former (PEG4000, X3, %) were taken as independent factors. The
      optimization model was f2 = -29.3 + 2.35X3 - 0.123X1(2) - 0.046X2(2) + 0.145X1X2
      (R = 0.996). It was found that the dissolution profile could match the target
      dissolution profile under the condition of weight gain 8%-9%, X1 (20-34), X2 (30
      57), X3 = 50. It is also found that the minimum usage percentage of pore former
      is 35.1%. The prediction results of the optimization model were good in the
      experiments.

PMID- 19408697
TI  - [New strategy to promote adult spinal cord regeneration: enhance adult neurons'
      intrinsic growth capability].
AB  - Injured adult spinal cord neurons are usually unable to regenerate their axons
      due to the inhibitory environment and low intrinsic regenerative capability. One
      of the main strategies to promote spinal cord regeneration is blocking and/or
      neutralizing the inhibitory factors or their common inhibitory signal pathway.
      However, overcoming inhibition alone is insufficient to cause extensive
      regeneration when neurons' intrinsic growth state has not been activated.
      Therefore, it becomes one of the most interested targets for promoting spinal
      cord regeneration that how to enhance adult neurons' intrinsic growth capability,
      such as elevating adult neuron cAMP/PKA level, blocking Rho/ROCK pathway,
      modulating transcriptional factors etc., such that they no longer response to
      inhibitory environment. In this paper we will review the current research
      findings and recent progresses in this field.

PMID- 19408698
TI  - [Glucocorticoids, adipose metabolism and insulin resistance].
AB  - Obesity, insulin resistance, and type 2 diabetes are associated with elevated
      concentration of circulating free fatty acid (FFA), which is critically governed
      by the process of triglyceride lipolysis in adipocytes. Endogenous and exogenous
      glucocorticoids excess could induce insulin resistance and diabetes. Thus, the
      effects of glucocorticoids stimulating adipose lipolysis and elevating FFA
      release may contribute to glucocorticoids-induced insulin resistance and
      diabetes. This review focuses on the regulation and function of glucocorticoids
      in adipose lipolysis and metabolism.

PMID- 19408699
TI  - [Progress in the research of ganglioside's biological activities].
AB  - Gangliosides (GS), a series of glycosphingolipids with sialic acids, are
      widespread in the cell membrane of tissues of the vertebrates, especially
      enriched in the brain of fetus and neonatal brains, therefore it's believed that
      GS may be associated with the neuronal differentiation, dendritogenesis and
      synapse formation. Earlier study had confirmed that GS could promote the
      regeneration of the nervous system and the synapse formation. With the
      development of the synthesis and molecular biological technique, researchers have
      found that GS are not only related to the development of neurons system and
      degenerative diseases such as Alzheimer's disease and Parkinson's disease, but
      also to the process of tumor invasion, which have attracted much attention in
      recent years. Intensive studies have been conducted on ganglioside concerning its
      chemical structure, pharmacological features and clinical application. This
      review summarizes the development of ganglioside's biological activities in
      recent ten years, including the research finding in our laboratory.

PMID- 19408700
TI  - [The advances of research on vestibulo-cardiovascular reflexes].
AB  - Vestibulo-cardiovascular reflexes (VCR) is a complex sensory-motor regulatory
      system, it refers to changes in body posture, adequate stimulus acting at
      vestibular receptor and regulation of cardiovascular functions including blood
      pressure, cardiac rhythm via autonomic center. Excessive vestibular stimulation
      or unilateral labyrinth lesion may cause paradoxical reaction including vertigo,
      tachycardia, etc. The evidences, significance, neural circuit, and
      neurotransmitters of VCR are reviewed in this paper.

PMID- 19408701
TI  - [Update on reassessment of dietary reference intakes (DRIs) for vitamin D].
AB  - The latest clinical studies show that vitamin D has many health promoting
      functions. However, the current dietary reference intakes (DRIs) of vitamin D is
      too low. In particular the maximum tolerable intake (UL) of vitamin D is too low,
      which hampers the clinical use of vitamin D as an nutrient and must be re
      assessed. We reviewed the average requirement (EAR) and the recommended intake
      (RNI) of vitamin D in children, adults, elderly and pregnant and parturient
      women, and encouraged to increase the recommended intake of vitamin D. We also
      reviewed the risk of high-dose vitamin D intake and suggested to raise the
      maximum tolerable intake (UL) made by American CRN. Finally, we propose that
      Chinese Nutrition Society will consider to increase the UL of vitamin D from 20
      microg to 50 microg.

PMID- 19408703
TI  - [Association of decreased ATP synthesis in mitochondria with pancreatic beta cell
      dysfunction].

PMID- 19408702
TI  - [Neutralizing science citation index as an academic evaluation system].
AB  - Research papers are published in thousands of scientific journals every year in
      the world. The quality of these papers has to be evaluated to determine their
      accuracy and contribution to their research fields. Science citation index (SCI)
      is a citation-based metric used to rank scientific journals. The importation of
      SCI from abroad contributed much both to encourage Chinese scientific community
      to collaborate with scientists all over the world, and the development of science
      and technology at home. However, there have been numerous criticisms over the
      years of the misuse of SCI, especially impact factor, as a measure of the quality
      of individual research papers. This review article analyzes the history and
      current situation of using SCI to evaluate scientific papers, discusses how to
      objectively consider SCI and the other new practices to evaluate research papers.
      It is also suggested in the present article that the impact of domestic
      scientific journals on the world should be improved, and that more attention
      should be paid to the quality of the research papers to improve the academic
      evaluation system and the development of science and technology in our country.

PMID- 19408704
TI  - [Endoplasmic reticulum stress and immune response after acute insults].

PMID- 19408705
TI  - [Reg family and pancreatic islet beta cell].

PMID- 19408706
TI  - [Purinergic signaling in nervous system].

PMID- 19408707
TI  - [Intra-amygdala GABAergic transmission and its role in fear extinction].

PMID- 19408708
TI  - [Autophagy in the pathogenesis of Parkinson's disease].

PMID- 19408709
TI  - [The relationship between PGE2 pathway and patent ductus arteriosus].

PMID- 19408710
TI  - [Physiological and molecular mechanisms of lifespan control in nematode
      Caenorhabditis elegans].

PMID- 19408711
TI  - [Uncoupling protein 4 (UCP4) in protection of mitochondria].

PMID- 19408713
TI  - [Effects of vagus nerve stimulation on memory].

PMID- 19408712
TI  - [Progress in research on the mechanisms of the gene regulation by microRNAs and
      TFs].

PMID- 19408714
TI  - [Application of computed tomography angiography in preoperative design of deep
      inferior epigastric artery perforator flap].
AB  - OBJECTIVE: To explore the application of computed tomography angiography (CTA) in
      preoperative design of deep inferior epigastric artery perforator (DIEAP) flap.
      METHODS: From Jan, 2007 to Mar, 2008, preoperative CTA of deep inferior
      epigastric artery was performed in 13 patients, including 5 patients with
      congenital absence of the vagina, 4 patients with penile and scrotal Paget's
      disease and 4 patients after mastectomy. The images were analyzed, including
      multiple planar reformation (MPR), maximum intensity projection (MIP) and volume
      rendering (VR). Then the distributions, branches and locations of perforators of
      deep inferior epigastric artery were measured. The images from CTA were compared
      with intraoperative observation. RESULTS: The images demonstrated the
      distributions of deep inferior epigastric artery and locations of its
      perforators, which were proved to be true by intraoperative observation.
      CONCLUSIONS: The preoperative CTA of deep inferior epigastric artery is very
      useful for preoperative design of DIEAP flaps.

PMID- 19408715
TI  - [Vaginal reconstruction with pedicled deep inferior epigastric perforator flap].
AB  - OBJECTIVE: To explore a new surgical procedure for vaginal reconstruction with
      pedicled deep inferior epigastric perforator (DIEP) flap. METHODS: Since June
      2007, 6 cases underwent vaginal reconstruction, including five congenital vaginal
      absence and one immediately after total vaginal resection due to carcinoma.
      Intensive CT scans were performed preoperatively for perforator selection. The
      DIEP flaps were designed vertically on the anterior abdominal wall and
      transferred for vaginal reconstruction. RESULTS: All the patients recovered
      uneventfully with no flap loss and other complication. The patients were followed
      up for 1 to 8 months (mean, 4 months) with satisfactory results. CONCLUSION:
      Vaginal reconstruction with vertical DIEP flaps is a safe and reliable method.

PMID- 19408716
TI  - [The gluteal perforator-based flap for repair of refractory wounds on different
      sites of buttocks].
AB  - OBJECTIVE: To discuss the application of perforator-based flap for repair of
      refractory sacral, ischial and trochanter wounds. METHODS: Vacuum sealing
      drainage (VSD) were applied for all the wounds for 6 - 21 days and cutaneous
      perforator was detected by Doppler before operation. According to the location of
      the perforator arteries, different types of perforator-based flaps were used to
      cover the wounds on the buttocks. RESULTS: Since 2005, 18 wounds in 14 patients
      were treated, including 11 sacral, 5 ischial and 2 trochanter defects. All flaps
      survived with primary healing.All the patients were followed up for 2 to 24
      months with no ulcer relapse. The colour and texture of the flaps were excellent
      with satisfactory cosmetic results. CONCLUSION: The gluteal perforator-based
      flaps have reliable blood supply with less morbidity in donor sites. It is an
      optimal method in repairing refractory wounds of the gluteal region.

PMID- 19408717
TI  - [Principles and techniques of plastic surgery in the treatment of patients
      injuried in the Wenchuan earthquake].
AB  - OBJECTIVE: To explore the role of plastic surgeon in the early intervention of
      soft tissue wound resulted from earthquake. METHODS: Firstly, the wounds were
      debrided completely. Based on the principles of plastic surgery, different
      methods were selected according to the types of the wounds. Primary closure was
      applied for wounds without any tissue defect. Skin grafts or flaps were needed
      for covering the soft tissue defect. Delayed wound closure was used for wounds
      with severe infection. RESULTS: 102 cases were treated. Primary healing was
      achieved in 76 cases. Infected or burned wounds were delayed closed after 2 - 3
      times of debridement and dress changing in 16 cases. All the flaps survived.
      Partial necrosis at the edge of the skin graft happened in 3 cases. 7 cases
      achieved delayed wound healing with skin graft or flap after VAC draining or
      dress changing. CONCLUSION: Satisfactory functional and cosmetic results can be
      achieved with the techniques of plastic surgeons. It has also important
      significance for the psychological recovering of the wounded in the earthquake.

PMID- 19408718
TI  - [One-staged orthognathic surgery and arthroscope-assisted condylar reconstruction
      with costochondral graft].
AB  - OBJECTIVE: To investigate one-staged orthognathic surgery and arthroscope
      assisted condylar reconstruction with costochondral graft for temporomandibular
      diseases combined with dental-maxillofacial deformities. METHODS: The
      preoperative measurement and model surgery was performed. The patients underwent
      arthroscope assisted condylar reconstruction with costochondral graft combined
      with bimaxillary surgery or mandibular surgery. RESULTS: From Sept. 2003 to Dec.
      2005, 15 cases were treated successfully with no bleeding, nerve injury and
      infection. The patients were followed up for 29 to 52 months (mean, 31.8 months).
      The appearance was markedly improved. TMJ function was good with no pain. The
      average maximum interincisal opening was 33.6 mm. CONCLUSION: Compared with
      traditional operation, one-staged orthognathic surgery and arthroscope-assisted
      condylar reconstruction with costochondral graft has its advantages. Indication
      selection and preoperative design are very important.

PMID- 19408719
TI  - [Transcranial surgical correction of cranio-orbital fibrous dysplasia with
      lateral orbital approach].
AB  - OBJECTIVE: To explore the transcranial surgical method with lateral orbital
      approach for the treatment of cranio-orbital fibrous dysplasia. METHODS: Lateral
      orbital transcranial extradural approach was adopted to correct complicated
      fibrous dysplasia in which the frontal, orbital, sphenoid, temporal bones were
      involved. Partial lesion removal and optic nerve decompression were performed
      through the transcranial extradural route by fronto-temporal cranial bone flap
      exposure. The fronto-orbital skeleton was shaped after bone flap deactivation.
      RESULTS: 8 cases were treated successfully with no complication. The period of
      follow-up ranged from 9 months to 3 years. The appearance and the vision improved
      greatly. Cranial CT showed good bony union with no relapse. CONCLUSIONS: Lateral
      orbital transcranial surgical approach is an optimal technique to correct cranio
      orbital fibrous dysplasia.

PMID- 19408720
TI  - [Correction of progressive hemifacial atrophy using dermis-fat graft and Medpor
      implant shaped by reverse engineering technique].
AB  - OBJECTIVE: To evaluate the therapeutic effect of dermis-fat graft combined with
      Medpor implant shaped by reverse engineering technique in the correction of the
      progressive hemifacial atrophy. METHODS: A skull model was made by rapid
      prototyping and the bony deficiency model was acquired with reverse engineering
      technique. The Medpor implant was shaped precisely based on the deficiency model
      and implanted with dermis-fat graft at the same stage. RESULTS: 11 cases were
      treated successfully without infection, necrosis and rejection. The patients were
      followed up for six months to one year with satisfactory cosmetic improvement.
      The dermis-fat graft survived without obvious absorption. CONCLUSION: The
      technique can correct both the bony and soft tissue deficiency for progressive
      hemifacial atrophy. It is very practical and easily performed with reliant
      results and less morbidity.

PMID- 19408721
TI  - [Application of multislice spiral CT and 3D reconstruction in diagnosis and
      treatment of vascular malformations in head and neck].
AB  - OBJECTIVE: To explore the application of MS-CT and 3D reconstruction in diagnosis
      and treatment of vascular malformations in head and neck. METHODS: 20 cases with
      vascular malformations in head and neck underwent MS-CT and 3-D reconstruction.
      Then the treatment was determined based on the results of MSCT scanning. The
      postoperative results were evaluated. RESULTS: The images of MS-CT showed the
      edge of vascular malformations partially or completely in 16 cases of venous
      malformations. The lesion's anatomic site and 3-D position was obtained. The 3-D
      images also showed the overexpanded supply arteries in 4 case of arteriovenous
      malformations. 2 case of venous malformations in lip underwent resection and
      healed completely. 12 cases of venous malformations in buccal and floor of mouth
      were treated with compartmentalized sclerotherapy with partial lesion involution.
      2 case of venous malformations in mouth floor were treated with operation
      followed by sclerotherpy with partial lesion involution. 4 cases of arteriovenous
      malformations were treated with Superselective Artery Embolization with partial
      lesion involution. CONCLUSION: MS-CT and 3D reconstruction can play an important
      role in diagnosis and treatment of vascular malformations in head and neck.

PMID- 19408722
TI  - [Relationship of nonsyndromic cleft lip and/or palate and poliovirus receptor
      related 1 exon 3 polymorphisms in Han people of Jiangzhe area].
AB  - OBJECTIVE: To study the relationship of nonsyndromic cleft lip and/or palate
      (NSCL/P) and poliovirus receptor-related 1 exon3 (PVRL1exon3) polymorphisms in
      Han People of Jiangzhe area. METHODS: PVRL1exon3 was examined by polymerase chain
      reaction-single strand conformation polymorphism (PCR-SSCP) technique in the 50
      patients with NSCL/P and 85 healthy parents. RESULTS: No W185X mutation was found
      in the PVRL1exon 3. CONCLUSION: It indicates that there is no relationship
      between NSCL/P and PVRL1exon3 in Han People in Jiangzhe area.

PMID- 19408723
TI  - [One-staged correction of alveolar cleft and lip and nasal deformities secondary
      to lip cleft].
AB  - OBJECTIVE: To investigate individualized one-staged correction of alveolar cleft
      and lip and nasal deformities secondary to lip cleft. METHODS: The alveolar cleft
      and lip and nasal deformities secondary to lip cleft were corrected in one stage.
      RESULTS: From 2004 to 2007, 37 cases were treated. 33 patients were treated
      successfully with primary healing in bony recipient area. Cancellous bone
      exposure happened in 3 cases. The wounds healed after debridement and drainage.
      The cosmetic results were satisfactory. CONCLUSIONS: One-staged correction of
      alveolar cleft and the lip and nasal deformities secondary to lip cleft can
      achieve good results.

PMID- 19408724
TI  - [Comparison of the mechanisms of intralesional steroid, interferon or verapamil
      injection in the treatment of proliferative scars].
AB  - OBJECTIVE: To investigate the effects of intralesional steroid, interferon alpha
      2b or verapamil injection on proliferation, apoptosis and TGF-beta1 expression in
      keloid and hypertrophic scar in vivo. METHODS: 6 patients with keloids and 6
      patients with hypertrophic scar were treated with intralesional injection of
      triamcinolone acetonide (40 mg/ml) or IFN alpha-2b (15 x 10(5) U/ml) or verapamil
      (2.5 mg/ml). Samples were collected on the 7th day after intralesional injection.
      Samples of untreated keloid and hypertrophic scar and normal skin were used as
      control. Expression of PCNA and TGF-beta1 was detected in situ by
      immunohistochemical staining, and apoptosis was detected in situ by terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end
      labeling (TUNEL). RESULTS: 1) Triamcinolone acetonide could prohibit
      proliferative scars through inhibiting cell proliferation and TGF-beta1
      expression, as well as inducing apoptosis. 2) IFN alpha-2b could prohibit
      proliferative scars through inhibiting cell proliferation and TGF-beta1
      expression, but not inducing apoptosis; 3) Verapamil could also prohibit
      proliferative scars through inhibiting proliferation and TGF-beta1 expression in
      fibroblasts, as well as inducing apoptosis. While the effect of inducing
      apoptosis was stronger than that of triamcinolone acetonide, the effect of
      inhibiting TGF-beta1 expression was weaker than those of triamcinolone acetonide
      and IFN alpha-2b. CONCLUSIONS: Although intraleional injection of steroid,
      interferon alpha-2b or verapamil were all effective in the treatment of keloid
      and hypertrophic scar, their mechanisms are not similar.

PMID- 19408725
TI  - [Expression of Notch receptors, ligands and downstream target genes in epidermis
      of hypertrophic scar].
AB  - OBJECTIVE: To study the expression of Notch receptors, ligands and downstream
      target genes in hypertrophic scar and normal skin, and to investigate its role in
      the development of hypertrophic scar. METHODS: By immunohistochemistry, the
      expression of epidermal differentiation markers- beta1 integrin, keratin 14 (K14)
      and keratin 19 (K19), as well as Notch 1-4 and Jagged1 were examined in
      hypertrophic scars and normal skins. The expression of Notch downstream genes-
      P21 and P63 was analyzed with real-time quantitative PCR and immunohistochemistry
      staining. RESULTS: Histological analysis revealed a significant epidermal
      thickening in the hypertrophic scars, with excessive cell layers above the basal
      layer. Compared to the normal epidermis, the expression of beta1 integrin, K19
      and K14 decreased in hypertrophic scars (P <0.05). Positive expression rate of
      Notch1 and Jagged1 in keratinocytes was significantly higher in hypertrophic scar
      than in normal skin (P < 0.05), while there was no difference in Notch2 and 3
      positive expression rate. Furthermore, the expression of P21 was significantly up
      regulated, while the expression of P63 was down-regulated in keratinocytes of
      hypertrophic scar (P < 0.05). CONCLUSIONS: Notch signal may play an important
      role in hypertrophic scar pathogenesis. Over-differentiation of Keratinocytes in
      hypertrophic scar may be related to the overexpression of Notch1 and Jagged1, up
      regulation of P21 gene and down-regulation of P63 gene.

PMID- 19408726
TI  - [Effect of recombinant Sp1 gene on the collagen expression of hypertrophic scar
      fibroblasts in vitro].
AB  - OBJECTIVE: To explore the feasibility of transfecting recombinant Sp1 into
      hypertrophic scar fibroblasts and investigate the proliferation and collagen I,
      III synthesis in the transfected cells. METHODS: Recombinant human Sp1 was
      transfected into hypertrophic scar fibroblasts with the karyocyte expressive
      vector. The expression of Sp1, collagen I, III mRNA was tested by real time PCR.
      The change of cell proliferation was observed with CCK8 colorimeter. RESULTS:
      About 30% of transfected hypertrophic scar fibroblasts showed green fluorescence
      positive. The relative expression of Sp1 mRNA in transfected cells, empty-vector
      cell or untransfected cells group was 5.26 +/- 0.76, 1.08 +/- 0.18, 1.09 +/-
      0.15, respectively, showing a significant difference between thansfected and
      untransfected cells or between the transfected cells and empty-vector group (P
      <0.01, n = 5). Expression of collagen I, III mRNA was 2.49 +/- 0.40 and 1.88 +/-
      0.30 in transfected cells, 0.96 +/- 0.18 and 0.95 +/- 0.18 in empty-vector cell,
      and 0.97 +/- 0.15 and 0.93 +/- 0.13 in untransfected cells, respectively, showing
      a significant difference between thansfected and untransfected cells or between
      the transfected cells and empty-vector group (P < 0.01, n = 5). CONCLUSIONS: The
      hypertrophic scar fibroblasts could be as the target cells of Sp1 gene
      transfection. Sp1 gene may play an important role in abnormal collagen metabolism
      in hypertrophic scar.

PMID- 19408727
TI  - [Effect of botulinum toxin type A on the expression of substance P, calcitonin
      gene-related peptide, transforming growth factor beta-1 and alpha smooth muscle
      actin A in wound healing in rats].
AB  - OBJECTIVE: To investigate the effect of botulinum toxin type A on the expression
      of substance P (SP), calcitonin gene-related peptide (CGRP), transforming growth
      factor beta-1 (TGF-beta1) and alpha smooth muscle actin A (alpha-SMA) in wound
      healing. METHODS: 60 rats were randomly divided into group C (control) group L
      (low-dose) and group H (high-dose), with 20 rats in each group. The wound-healing
      model was established by excision of four full-thickness skin (1 cm x 1 cm,
      around the injection site) on the back of all SD rats on the 7th day after BTA
      injection. The wound size was measured and the expression of SP, CGRP, TGF-beta1
      and alpha-SMA in wound granulation tissue was assayed by immunohistochemical
      staining and computerized image analysis before operation, and 3 days, 7 days and
      14 days after operation. RESULTS: All the wounds healed 14 days after operation.
      The wound size in L and H group was not significantly different with that in C
      group on the 3rd day and 7th day after operation. The positive immuno-staining of
      SP, CGRP, TGF-beta1 and alpha-SMA in group L and H was significantly weaker than
      those in C group. Meanwhile, the positive immuno-staining of all above substances
      in H group was weaker than those in L group significantly. CONCLUSIONS: Botulinum
      toxin type A can decrease the expression of SP, CGRP, TGF-beta1, and alpha-SMA in
      wound healing in a dose-dependent manner with no effect on the healing time.

PMID- 19408728
TI  - [Reconstruction of rabbit urethra using urethral extracellular matrix].
AB  - OBJECTIVE: To evaluate the feasibility of reconstruction of rabbit urethra using
      urethral extracellular matrix. METHODS: Extracellular matrix was obtained from
      the urethra of 20 donor New Zealand rabbits. In experimental group, 20 rabbits
      underwent segmental urethral resection (about 1.0 to 1.5 cm in length) and the
      defects were replaced by a tube of extracellular matrix. The serum TNFalpha was
      detected by ELISA to assess the immunity response preoperatively and 12, 24, 48 h
      postoperatively. The regenerated urethral segments were taken for histologic and
      pathologic study 10 days, 3 weeks, 6 weeks and 24 weeks after operation. The
      urodynamics, urethroscopy and urethrography were also performed. RESULTS: The
      serum TNFalpha in experiment group slightly rised, with no significant difference
      when compared with that in control group. 10 days after operation, epithelial
      cell migrated into the extracellular matrix from two ends, and small vessels were
      also found. 3 weeks later, several layers of urothelium covered the whole surface
      of the matrix tube. 6 weeks later, the irregularly arranged smooth muscle fibers
      were fist observed by Van Gieson staining. 24 weeks after operation, the smooth
      muscle cells increased, the appearance of the regenerated urethra segments were
      very similar to normal urethral wall components. The urethrography and urodynamic
      evaluation revealed no difference between the normal and the regenerated urethral
      tube. CONCLUSIONS: The urethral extracellular matrix might be an ideal
      replacement material for urethral defect.

PMID- 19408731
TI  - [Gastrointestinal bleeding of obscure origin].

PMID- 19408729
TI  - [The effect of focal-adhesion micromanipulation in trauma and wound healing].
AB  - OBJECTIVE: To explore the effect of focal-adhesion micromanipulation on the
      biological behavior of fibroblast. METHODS: Micro-pot was made by microcontact
      printing. The molecules of constitutive protein was adhered on micro-pot by self
      assemble of peptides. Skin fibroblasts were cultured on the membrane by self-made
      biomechanical cell culture for 2 weeks. Morphology observation and cell
      immunohistochemistry analysis was performed. RESULTS: After 2 weeks, the
      morphology of the fibroblasts was diverse and more compliant. Cell
      immunohistochemistry analysis found that the expression of integrinbeta1, alpha5
      and tensin was dramatically reduced. CONCLUSIONS: The morphology and the
      biological behaviour of the fibroblasts in hypertrophic scar can be changed after
      micromanipulation of focal adhesion.

PMID- 19408730
TI  - [Endoscopic images of jejunum in patients with small bowel transplantation].

PMID- 19408732
TI  - [An unusual cause of pancreatitis].

PMID- 19408733
TI  - [Why are there few publications by the Argentine gastroenterology? Considerations
      on a bibliometric analysis of Argentine publications on gastroenterology].
AB  - The publication of scientific findings is the main way to communicate advances.
      Our aim was to perform a bibliometric and comparative analysis of the Argentinean
      gastroenterological research output. We analyzed Argentinean gastroenterological
      publications selectively retrieved from LILACS (between years 1982-2006) and
      EMBASE (1996-2007) databases by means of specially constructed filter based on
      author address and subject headings. The global Argentinean scientific research
      output is far below that of developed countries and has been affected in direct
      manner by economic, political and social disturbances in the country. The
      gastroenterological research output from Argentina represent about 6% of national
      biomedical research. While 54% belongs to gastroenterology and 46% to hepatology,
      65% are based on clinical research and 67% were originally contributions. Only
      11% have been published in high impact factor journals. The comparative analysis
      within countries with health indicators similarities has shown a low biomedical
      and gastroenterology research output, however, the rate of acceptance at the 18
      top gastroenterological journals is acceptable (15%). The contributions of
      registered specialists were lower for gastroenterologists compared with those
      from hepatologists (8.7% and 16.4% respectively). The research projects at public
      hospital funded by the pharmaceutical industry overcome those funded
      independently. Indeed, it seems that the independent research is being
      progressively replaced by that supported by the industry due to economic benefits
      for researchers even when there is a very low participation rate in publications
      (3%) by Argentinean researchers. We conclude that the Argentinean biomedical and
      gastroenterological research output is scanty compared with developed countries
      and countries with comparable health indicators. Our analysis suggests that
      efforts must be taken to attain objectives directed to develop and improve the
      Argentinean biomedical and gastroenterological scientific work and publication.

PMID- 19408734
TI  - [Historical review: Enrique Finochietto].

PMID- 19408735
TI  - [Balloon-assisted sphincterotomy in patients with Billroth II gastrectomy and
      common bile duct stone: a new method].
AB  - INTRODUCTION: diagnostic and therapeutic ERCP in patients with Billroth II
      gastrectomy is a challenging procedure due to anatomic alterations. New
      accessories and techniques were developed in order to minimize these adversities.
      AIM: a new technique for biliary access in patients with Billroth II gastrectomy.
      PATIENTS: In the period from February 2003 to August 2007, 257 ERCP presented
      Billroth II gastrectomy and choledocolithiasis. In 37 of these patients
      catheterization by conventional technique was not possible and they were
      submitted to the new technique. METHODS: after fistulotomy in order to access
      CBD, a 0.035-inch guidewire was passed followed by an 8-mm dilator biliary
      balloon which was settled in transpapillary position. Through the working channel
      the knedle-knife was passed which when positioned in front of the papilla allowed
      the section of the sphincter over the balloon inflated with contrast until waist
      disappearance on radioscopy. RESULTS: of the 37 patients submitted to the new
      procedure six were excluded. Sixteen patients (61.6%) were female and fifteen
      (48.4%) male. Age ranged from 29 to 89 years with a mean of 62.3 years. All
      patients had jaundice by clinical and laboratory tests. Time of procedure varied
      from 18 to 48 minutes (30 minutes). Diameter of the bile duct was 4.5 to 12.8 mm
      (7.7 mm) presenting one to seven calculi. There were occurred six (19.3%)
      complications related to the procedure, three (9.7%) pancreatitis, two (6.4%)
      hemorrhages and one (3.2%) perforation. There were no procedure-related deaths.
      CONCLUSION: success of this technique was 83.8% (31 of the 37 cases); therefore
      the technique is considered a safe and efficient method in patients with Billroth
      II and difficult duodenal papilla cannulation and it was previously attempted by
      means of conventional cannulation technique.

PMID- 19408736
TI  - [Is the prophylactic antibiotic therapy with Imipenem effective for patients with
      pancreatic necrosis?].
AB  - OBJECTIVE: to evaluate the capacity of Imipenem as a prophylactic treatment for
      decreasing the number of infected necrosis and surgeries, as well as for
      diminishing septic complications and the mortality rate among patients with
      severe acute necrotizing pancreatitis. MATERIAL AND METHODS: from May 2005 to
      December 2007 a prospective randomized study was conducted in order to evaluate
      the efficacy of a prophylactic antibiotic therapy in patients with pancreatic
      necrosis. During this time period 58 patients entered the study protocol.
      Patients were divided in two groups; the first one underwent antibiotic therapy
      with Imipenem while the second group received no prophylactic treatment at all.
      All patients received early enteral nutrition. RESULTS: both studied groups had
      comparable age, gender ratio, and C.R.P and necrosis percentages. When comparing
      general morbidity in both groups no difference was found between the group
      receiving a prophylactic antibiotic and the group that did not receive it (58%
      vs. 56%). Moreover, when the septic complications were evaluated, it was
      confirmed that these were more frequent among the group of patients receiving
      Imipenem (29%), in comparison to the group that did not received antibiotics
      (15%). 12.5% of the patients that received Imipenem developed pancreatic necrosis
      infection, while said infection only appeared in 6% of the patients in the group
      that did not receive antibiotic prophylaxis; nevertheless, none of the
      comparisons reached statistical significance. The number of patients who required
      surgery was similar in both groups. When comparing the hospital stay, it was
      observed that this was longer among the patients receiving prophylactic therapy.
      No patient died during the study. CONCLUSION: The present study finds no benefits
      in the use of antibiotic therapy with Imipenem regarding the risk of developing
      pancreatic necrosis infection and septic complications, and neither when trying
      to reduce the number of surgeries among patients with severe acute pancreatitis
      with necrosis.

PMID- 19408737
TI  - [Insulin-like growth factor-binding protein-1: a new biochemical marker of
      nonalcoholic fatty liver disease?].
AB  - AIM: to assess the presence of nonalcoholic fatty liver disease in patients with
      risk factors for this pathology (obesity, dyslipidemia, metabolic syndrome and
      diabetes type 2) and to determine the role of insulin, HOMA index, insulin-like
      growth factor-binding protein-1, sex hormone-binding globulin and plasminogen
      activator inhibitor type 1, as biochemical markers. METHODS: Ninety-one patients
      with risk factors for nonalcoholic fatty liver disease were evaluated. Serum
      transaminases, insulin, sex hormone-binding globulin, insulin-like growth factor
      binding protein-1 and plasminogen activator inhibitor type 1 were measured. The
      diagnosis of fatty liver was performed by ultrasonography and liver biopsies were
      performed to 31 subjects who had steatosis by ultrasonography and high alanine
      aminotransferase. RESULTS: Nonalcoholic fatty liver disease was present in 65 out
      of 91 patients (71,4%). Liver biopsy performed to 31 subjects confirmed
      nonalcoholic steatohepatitis. Twenty-five patients had different degrees of
      fibrosis. Those individuals with fatty liver had higher waist circumference,
      serum levels of triglycerides, insulin and HOMA index, and lower serum insulin
      like growth factor-binding protein-1 concentration. The degree ofhepatic
      steatosis by ultrasonography was positively correlated to waist circumference,
      triglycerides, insulin and HOMA index (p<0,003; p<0,003; p<0,002 and p<0,001,
      respectively), and was negatively correlated to HDL-cholesterol and insulin-like
      growth factor-binding protein-1 (p<0,025 and p<0,018, respectively). CONCLUSIONS:
      We found a high prevalence of NAFLD in patients with risk factors, most of them
      overweight or obese. Although SHBG and PAI-1 have a closely relationship to
      insulin resistance, they did not show to be markers of NAFLD. Regardless of low
      IGFBP-1 levels associated with NAFLD, serum IGFBP-1 measure is less accessible
      than insulin and triglycerides levels, HOMA index and waist circumference.
      Moreover, it is not a better marker for NAFLD than the above mentioned.

PMID- 19408738
TI  - [Assessment of respiratory muscle strength, peak expiratory flow and pain after
      open cholecystectomy].
AB  - OBJECTIVE: to investigate the behavior of maximal inspiratory and expiratory
      pressure (MIP and MEP), peak expiratory flow (PEF) and pain after open
      cholecystectomy. METHODS: were investigated 31 volunteers over 18 years submitted
      to open cholecystectomy between january and december 2007 at Holy House of
      Charity in the city of Diamantina-MG. The MIP MEP PEF and pain variables were
      measured at times pre-operative, 24 and 48 hours post-operative using
      manovacuometer, peak flow meter Assess and visual numeric scale of pain
      respectively. The statistical analysis was performed using Wilcoxon and Spearman
      tests considering significant differences for p<0,05. RESULTS: There was
      significant reduction of the MIP MEP and PEF values at 24 and 48 hours post
      operative compared to the pre-operative values. The levels of pain were
      significantly higher at all post-operative times compared to the pre-operative
      time. The MIP, MEP and PEF measures not showed correlation with the levels of
      post-operative pain. Nevertheless, the PEF after surgery showed significant
      correlation with the MEP values. CONCLUSION: the open cholecystectomy causes
      significant impairment of the respiratory muscle strength and the peak expiratory
      flow at all post-operative times evaluated, with more pronounced reductions at 24
      hours post-operative. The MIP MEP and PEF measures presented a different behavior
      compared to pain evaluation at all times investigated.

PMID- 19408739
TI  - Etiology of hepatocellular carcinoma in Argentina: results of a multicenter
      retrospective study.
AB  - Incidence and etiology of hepatocellular carcinoma (HCC) are variable around the
      world, depending mainly on theprevalence ofchronic hepatitis B carriers in each
      region. No study has been published analyzing epidemiological features of
      patients with HCC in Argentina. The aim of this retrospective study was to
      describe demographical and etiological results in a series of 587 consecutive
      patients with HCC diagnosed in 15 Hepatology and Gastroenterology Units
      distributed all around our country. Seventy-two per cent of patients were male,
      the median age was 62 years (interquartile range 55-68 years), and 93% had
      cirrhosis. Regarding to etiological data (fully available in 551 cases), main
      etiologies were chronic alcoholism in 229 patients (41.6%) (the sole risk factor
      in 182, associated to HCVin 35 and to HBV in 12); hepatitis C in 223 patients
      (40.5%) (the sole risk factor in 181, associated to alcoholism in 35 and to HBV
      in 7); hepatitis B in 74 patients (13.4%) (the sole risk factor in 55, associated
      to alcoholism in 12 and to HCV in 7); cryptogenic cirrhosis in 51 patients
      (9.2%). There were significant differences in percentages of genders between main
      groups: males were highly predominant in alcoholic cirrhosis (93%), hepatitis B
      (87%) and HCV plus alcohol (94%), compared to 63% in cryp togenic cirrhosis and
      49% in hepatitis C (p<0.01). There were no differences in age at presentation
      between the main etiologies. In conclusion, the main causes of HCC in Argentina
      are alcoholic cirrhosis and hepatitis C (76% of cases). A majority of patients
      with HCC in our country are cirrhotics, males, and in their 6th or -7th decades
      of life.

PMID- 19408740
TI  - [Celiac crisis: presentation as bleeding diathesis].
AB  - Celiac crisis is a severe and potentially fatal complication of celiac disease.
      Unusual at present, it has been described mainly in children younger than 2-years
      old, but reports in adults do exist. We report a 26-years-old lady with tetany
      and bleeding diathesis at presentation. In spite of it rareness, it is important
      to consider celiac crisis among the multiple manifestations of celiac disease.

PMID- 19408741
TI  - [Genetic alterations, genomic instability and cancer in celiac disease].
AB  - Celiac disease (CD) is a common autoimmune disorder characterized by intestinal
      inflammation and mucosal atrophy triggered by dietary gluten in genetically
      predisposed individuals. Although, most patients improve with a gluten-free diet,
      a small percentage (2-5%) develops refractoriness or pre- and malignant
      complications. Malignancies are the most serious complications of CD, including
      gastrointestinal carcinomas and non-Hodgkin lymphoma, particularly Enteropathy
      type T-cell lymphoma, a rare high-grade T-cell non-Hodgkin lymphoma of the small
      intestine, almost exclusively observed in CD patients. The molecular basis behind
      cancer development in CD is not known. To really understand CD-cancer biology it
      is important to known all of its genetic and genomic alterations. Carcinogenesis
      involves the acquisition of multiple genetic changes that create a background of
      genetic instability which accelerate the accumulation of subsequent mutations.
      Two major modes of genome destabilization have been recognized: microsatellite
      instability and chromosome instability (CIN). A review of genetic abnormalities
      reported in CD, refractory sprue or CD-associated tumors, suggests that a CIN
      phenotype is implied in malignant transformation in CD. Moreover, our recent
      findings showing that a group of untreated CD patients exhibits genomic
      instability at nucleotide level, affecting specific microsatellite loci, provides
      evidence of molecular alterations in non-malignant CD cells. In conclusion, most
      genetic studies, point to the role of chronic inflammation in the induction of
      genomic instability and malignant emergence in at-risk individuals.

PMID- 19408742
TI  - [Intestinal transplant. Review and description of its evolution in Latin
      America].
AB  - Intestinal failure remains a cause of morbidity and mortality in children and
      adults. Currently intestinal failure patients must be evaluated by a
      multidisciplinary team in order to optimize parenteral support, to determine the
      chances for rehabilitation or the need for transplantation. Intestinal transplant
      has been the last abdominal organ to evolve. Indications and procedures have been
      refined and standardized; new immunosuppressive drugs and the experience of
      treating these patients in a limited number of centres have reduced complications
      and improved survival. Forty years after the first attempt, intestinal transplant
      can now be successfully performed in Latin-America. The aims of this review are
      to update the current status of intestinal transplant, to highlight new
      developments and the evolution in our continent and to provide the basic
      knowledge in the management of intestinal failure patients for nutritionists,
      gastroenterologists and surgeons.

PMID- 19408743
TI  - [Genomics arrives to the clinical practices in colorectal cancer].

PMID- 19408744
TI  - [Therapeutic choice of lumbar intervertebral disc herniation].

PMID- 19408745
TI  - [Analysis of curative effect of discectomy for lumbar intervertebral disc
      herniation].
AB  - OBJECTIVE: To evaluate the short and long term results of discectomy for lumbar
      intervertebral disc herniation. METHODS: From 2000 to 2007, 400 patients (male
      220 and female 180, the age was from 16 to 73 years old with an average of 42.3
      years) with lumbar intervertebral disc herniation underwent discectomy by
      posterior mini-incision less than 5 cm and vertebrae plate was ectomized in 2 cm
      x 2 cm winder,and nerve root was compressied. The short and long term clinical
      result were analyzed with SPSS 10.0 software. RESULTS: Three hundred and eighty
      patients were followed up in the short term (less than 2 years after operation),
      308 cases obtained excellent result, 48 good, fair 24, the excellent and good
      rate was 93.7%. Three hundred and forty-eight patients were followed up in the
      long term (more than 3 years after operation), 244 cases obtained excellent
      result, 48 good, fair 56,the excellent and good rate was 83.9%. There was
      significant difference in follow-up between the short and long term (P < 0.05).
      CONCLUSION: The clinical effect of discectomy for lumbar intervertebral disc
      herniation decreased with time lapse.

PMID- 19408746
TI  - [Analysis of intermediate and long term clinical effects on discectomy with
      diskoscope].
AB  - OBJECTIVE: To estimate intermediate and long term clinical effects of lumbar
      intervertebral disc herniation on discectomy with diskoscope. METHODS: A hundred
      and nine patients with lumbar intervertebral disc herniation were retrospectively
      analyzed. The patietnts were operated with diskoscope. There were 61 males and 48
      females. The age was from 25 to 68 years old with an average of 37.7 years. The
      affected region of patients were L(3,4) (5 cases), L(4,5) (42 cases), L5S1 (49
      cases), L(4.5) and L5S1 (13 cases). Among them, 88 cases with single side and one
      segment, 13 cases with homolateral and two segments, 8 cases with hibateral and
      one segment were operated. The curative effects were followed up and estimated by
      recording satisfaction degrees at 1 year and 5.2 years(average) after operation.
      Moreover,intervertebral space height and the spinal stability of the patients
      were compared by imaging data before and after operation. RESULTS: At 1 year and
      5.2 years (average) after operation,the scores by JOA standard were improved from
      6.40 +/- 1.68 to 13.40 +/- 1.42, 13.15 +/- 1.35 (P < 0.01) respectively;the
      scores by VAS standard were reduced from 7.10 +/- 1.55 to 1.90 +/- 0.84, 2.10 +/-
      0.58 (P < 0.01) respectively; the excellent and good rate was 91.7% (100/109) and
      89.9% (98/109) respectively; the satisfaction degree of the patients was 95.4%
      and 94.5% respectively. The average time before working was 1 month. The imaging
      data of 45 patients were complete in the study, no lumbar instability sign were
      found. The loss rates of intervertebral space height were 57.8% (26/45), 93.3%
      (42/45) respectively at 1 year and 5.2 years (average) after operation.
      CONCLUSION: Discectomy with diskoscope has a good intermediate and long term
      clinical effects, it is a reliable method in the treatment of lumbar
      intervertebral disc herniation. It doesn't uncertainly cause instability of
      intervertebral space and root compression, though it can't avoid the loss of
      intervertebral space height.

PMID- 19408747
TI  - [Clinical analysis of lumbar intervertebral disc herniation in adolescent with
      manipulation and traditional Chinese medicine].

PMID- 19408748
TI  - [The observe of clinical effect of treating lumbar intervertebral disc herniation
      by bone setting manipulation of different directions].
AB  - OBJECTIVE: To compare the effect between lumbar backwards flexion manipulation
      and rotating manipulation for treating lumbar intervertebral disc herniation.
      METHODS: Two hundred and nine patients of lumbar intervertebral disc herniation,
      male 131, female 78, the age from 20 to 79 years old, 58 cases of all these
      patients age above 50. According to diagnosis the ladder of the 92 cases bulging
      type, 69 hernia type, 48 cases free type. The patients were randomly divided into
      treatment group (107 cases) and control group (102 cases). All the patients were
      treated with the three-dimensional computer-controlled traction therapeutic
      apparatus, with continued traction for 30 minutes. After traction, lumbar
      backwards flexion manipulation and rotating manipulation were respectively
      adopted in treatment group and control group (on alternate days one time, 3 times
      as a course of treatment). The symptoms and signs (including back pain and
      discomfort, lower limb pain and numbness, powerless urination and defecation,
      numbness in perineum, straight-leg raising degree, ability of lower extremity
      walking, work and live) of patients were observed after treatment. RESULTS: All
      the patients were followed up from 1 to 6 months with an average of 3.2 months.
      After treatment, the symptoms and signs of patients have markedly improved (P <
      0.01), but the lower back pain and discomfort, lower limb walking ability in
      treatment group were better than control group (P < 0.05). According therapeutic
      criteria, the effect of treatment group was better than of control group (P <
      0.01). In cases with bulging type, 47 in treatment group and 45 in control group,
      the effect of treatment group was better than of control group (P < 0.05); in
      cases with hernia type, 35 in treatment group and 34 in control group, there was
      no significantly difference in effect between two groups (P > 0.05); in cases of
      free type, 25 in treatment group and 23 in control group, there was no
      significantly difference in effect between two groups (P > 0.05). CONCLUSION: The
      global effect of lumbar backwards flexion manipulation was satisfactory than
      rotating manipulation for treating lumbar intervertebral disc herniation. But
      rotating manipulation suited to free type.

PMID- 19408749
TI  - [Imaging manifestation and clinical value in herniation pit of femoral neck].
AB  - OBJECTIVE: To discuss the imaging manifestation and clinical value in herniation
      pit of femoral neck. METHODS: One case proved by operation and pathology and
      twenty cases with typical imaging manifestation described by Pitt were reviewed
      retrospectively. There were 17 males and 4 females with an average age of 53
      years old(ranging from 30 to 85 years). All cases were examined by X-ray films
      and CT, and 13 cases were performed with MRI. RESULTS: Twenty-nine lesions were
      found in the 21 cases, 9 cases were in right side, 8 cases were in left side, 4
      cases were in both sides. The lesions were all located in the superior lateral
      part of the femoral neck and anterior lateral base of femoral head. The lesions
      were round or oval, and most of their greatest diameter was less than 16 mm. X
      ray films showed a central radiolucency with a thin clear sclerotic rim or simple
      sclerotic loop. CT scans showed a well-defined lesion of soft-tissue attenuation
      with sclerotic margin. The lesions had focal cortical perforation. On MRI
      images,most lesions showed uniformly long T1 and long T2 fluid signal intensity.
      CONCLUSION: Herniation pit of femoral neck have some specific imaging features,
      CT can make accurate diagnosis. X-ray and MRI are helpful to diagnosis.

PMID- 19408750
TI  - [Application of elastic stable intramedullary nailing in treating femoral shaft
      fractures in children].

PMID- 19408752
TI  - [Apoptosis induction of traditional Chinese herb pianzihuang ([Chinese
      characters: see text]) in human osteosarcoma U-20S cells].
AB  - OBJECTIVE: To study the effect of apoptosis induction of pianzihuang in human
      osteosarcoma U-20S cells. METHODS: Sixth SD rats were randomly divided into group
      A (8 rats) and group B (8 rats) in the study. Among them, 8 rats (group A) were
      treated with PBS and 8 rats (group B) treated with pianzihuang. (2) Human
      osteosarcoma U-2OS cells were cultured in nutrient solution (including fetal calf
      serum of 10%, penicillin of 100 IU/ml, streptomycin of 100 microg/ml), the
      environmental condition in saturated humidity 5% CO2, 37 degrees C. The
      osteosarcoma U-2OS cell proliferation effect by different saturation of blood
      serum was measured by MTT method. And the optimal concentration of the serum
      (including Pianzihuang) could be obtained. (3) The morphous of osteosarcoma U-2OS
      cell were observed by inverted phase contrast microscope and electron microscope.
      (4) Apoptosis cell was detected by TUNEL in situ end labeling. (5) Extracted
      DNA,agarose gel electrophoresis (AGE) to detect apoptosis cell by transmission
      electron microscope (TEM). RESULTS: (1) It was best that osteosarcoma U-2OS cell
      proliferation effect by 20% of the concentration of the serum (including
      Pianzihuang). (2) On inverted phase contrast microscope showed that the cells of
      group A were fusiform adherence growth; the cyton transform shrind and circle in
      20% of the concentration of the serum (including Pianzihuang). Follow lasting
      time,the cell turning circle gradually increased. Necrosis cell and fragment were
      found by microscope. (3) The detected result of apoptosis cell in 20% of the
      concentration of the serum(including Pianzihuang) was positive by TUNEL assays.
      (4) AGE showed "ladder" strand of DNA, a special phenomenon of cellular
      apoptosis. (5) Chromatin aggregated along corrugativus caryotheca and apoptotic
      body appeared on cell surface by observation of TEM. CONCLUSION: Pianzihuang can
      inhibit proliferation and induce apoptosis for osteosarcoma U-2OS cell.

PMID- 19408751
TI  - [Diagnosis and treatment of the metacarpophalangeal joint locking caused by
      sesamoid turned-over dislocation of the thumb].
AB  - OBJECTIVE: To introduce diagnosis and treatment of the metacarpophalangeal joint
      (MPJ) locking caused by sesamoid turned-over dislocation of the thumb. METHODS:
      Five cases with metacarpophalangeal joint locking were involved in the study,
      male 4 and female 1. The average age was 35 years old(ranging from 18 to 47
      years). All the patients received manual reduction under local anaesthesia. But
      only three were successful, others patients were reduced by operation.
      Metacarpophalangeal joint locking caused by sesamoid turned-over dislocation with
      the volar plate and the short flexor muscle of the thumb tendon were reveded. The
      metacarpophalangeal joint locking was released after reduction of sesamoid turned
      over dislocation of the thumb. RESULTS: The mean follow-up time was 15 months (3
      34 months). The mean range of MPJ flexion was 45 degrees (35 degrees - 60
      degrees). The signs for pain and swelling were released. Satisfactory thumb
      opposition can be seen. CONCLUSION: It was one of the important reasons of the
      metacarpophalangeal joint locking caused by sesamoid turned-over dislocation of
      the thumb.

PMID- 19408754
TI  - [Partial excision of nail plate, onychostroma combined with reconstruction of
      nail groove for the treatment of severe ingrowing nail].

PMID- 19408753
TI  - [Clinical experience of nonselective replantation with severed distal finger
      segment].

PMID- 19408755
TI  - [Effect of total flavone of Epimedium on expression of bone OPG, OPGL mRNA in
      ovariectomized rats].
AB  - OBJECTIVE: To investigate the molecular mechanism of TFE (total flavone of
      epimedium) in the treatment of osteoporosis, and then provide experimental
      evidence for modernization and further development of TFE as an traditional
      Chinese medicine. METHODS: Sixty healthy female SD rats with aged 4 months were
      randomly divided into three groups (including control group in which rats
      received sham surgery, OVX group in which ovariectomized rats didn't give any
      medicine after the removal of ovaries and TFE group in which ovariectomized rats
      administrated TFE), 20 rats in each group. Compared bone mineral density (BMD)
      between before operation and at 4th week after operation in order to verify the
      establishment of osteoporotic model (criteria: BMD decreased more than 20% at 4th
      week after operation). The rats in TEF group were administrated total flavone of
      epimedium(concentration 30 mg/ml, 10 ml/kg, qd) orally for 4 weeks. After this,
      killed rats to harvest the lower part of the femur and detected BMD again.
      Applying the reverse transcriptase-polymerase chain reaction technique (RT-PCR)
      to detect expression of OPG, OPGL mRNA in bone tissue. RESULTS: (1) At 4th week
      after ovariectomy, the mean BMD of lumbar vertebra in TFE group fell to (0.084 +/
      0.020) g/cm2. Administrated with TFE for 4 weeks,the BMD increased to (0.112 +/-
      0.009) g/cm2. There was significant improvement compare with the OVX group (P <
      0.05). (2) Compared between OVX group and TFE group, The OPG mRNA expression of
      TFE group obviously enhanced. There was significant difference in statistics (P <
      0.05). However,the promotion for OPGL mRNA expression were detected between OVX
      group and TFE group,there was no significant difference in statistics (P > 0.05).
      CONCLUSION: This study showed that TFE could inhibit differentiation and
      maturation of osteoclast through enhancing OPG mRNA expression, accordingly,to
      treat osteoporosis.

PMID- 19408756
TI  - [Individualized treatment of lumbar intervertebral disc herniation].
AB  - OBJECTIVE: To investigate the necessity, practicability for individualized
      treatment of lumbar intervertebral disc herniation and analyze its clinical
      effect. METHODS: Five hundred and three cases of lumbar intervertebral disc
      herniation from March 2005 to March 2008 were individually treated by
      conservative treatment, minimal surgical procedures, open operation according to
      the protrusible size, rupture status of annular fibrosus, liberation or prolapse
      of disk tissue, accompanying conditions like spinal stenosis, spondylolisthesis
      or nerve involvement. Three hundred and ninety-three cases (male 189, female 204)
      were followed with an average age of 44.6 years old (range from 23 to 76). Among
      them, 210 cases were treated by conservative method, 145 cases by minimal
      surgical procedures and 38 cases by open operation. Therapeutic effect was
      evaluated by Macnab criteria. RESULTS: The mean follow-up duration was 16 months
      (range from 3 months to 3 years). Therapeutic effect was noted as 346 of
      excellence, 29 of effective, 18 of ineffective. Excellence rate was 88%(346/393)
      and effective rate was 95% (375/393). No severe complication was found. The
      recurrence rate of conservative treatment, minimal surgical procedures, open
      operation was respectively 18.1% (38/210), 9.6% (14/145), 5.3% (2/38).
      CONCLUSION: Conservative treatment is generally applied, its effect is reliable
      for patients of mild symptom. Minimal surgical procedures is applied more and
      more wide, the method will become prevalent. The indications for open operation
      became stricter and traditional surgical methods was challenged by less invasive
      methods. Individualized treatment basing on indication judgment was the most
      importance to improve therapeutic effect.

PMID- 19408757
TI  - [The history and principle of spinal manipulation in the treatment of lumbar
      intervertebral disc herniation].
AB  - It is generally agreed that spinal manipulation has been applied into the
      treatment of lumbar intervertebral disc herniation (LDH) for thousands of years
      according to historical reviews of the paper. The balance restore of spinal
      column had been always the main aim of spinal manipulation during the time. The
      situation has been changed after LDH was discovered pathomechanically about 70
      years ago and the protruded nucleus pulposus has attracted the attention of whole
      world ever since and surgery become the major choice for LDH patients.
      Nevertheless, some latest reports of clinical observation in past decades
      explored more and more solid evidences to prove that most of the patients need no
      surgery at all and would be cured by conservative therapy without any changes of
      protruded nucleus pulposus at involved segment. The modern management of LDH
      suggests that we should not only pay attention to the protruded disk but also to
      the biomechanical balance of spinal column again as we had for thousands of
      years,which is concluded from the reviews of previous reports and history of LDH
      recognition in the paper. The only thing we should care more about is how to make
      full use of our modern knowledge to adjust our view of observation and management
      in clinical practice of spinal manipulation and to make a further understanding
      of the pathomechanics of LDH.

PMID- 19408758
TI  - [Imaging study of lumbar intervertebral disc herniation and asymptomatic lumbar
      intervertebral disc herniation].
AB  - OBJECTIVE: Using regional assignment to forked method to study lumbar
      intervertebral disc hemiation (bugle, hernia, prolapse) dependablity and reason
      of lumbar intervertebral disc herniation and asymptomatic lumbar intervertebral
      disc herniation. METHODS: From March 2005 to October 2006, 120 patients of match
      condition from orthopaedics dept and rehabilitative dept of the Boai hospital of
      Longyan were studied. All patients were equally divided into two groups according
      to whether or not accompany with symptom of lumbar intervertebral disc
      herniation. There was not statistical difference in sex, age, course of disease,
      segment of intervertebral disc between two groups. Sixty patients of symptomatic
      lumbar intervertebral disc herniation were equally divided into three groups
      according to (bugle, hernia, prolapse) image on CT. Sixty patients of
      asymptomatic lumbar intervertebral disc herniation were equally divided into
      three groups according to (bugle, hernia, prolapse) image on CT. The age was 20
      59 years old with an average of 38.5 years. Using regional assignment to give a
      mark respectively for every group. The sagittal diameter index (SI), anterior
      diastema of flaval ligaments, the width of superior outlet of latero-crypt,
      anteroposterior diameter of dura sac were respectively measured by sliding
      caliper. CT value and protrusible areas were respectively evaluated by computer
      tomography. Adopting mean value to measure three times. RESULTS: (1) There were
      not statistical difference in SI, CT value, hernia areas, anteroposterior
      diameter of dura sac between two groups (symptomatic lumbar intervertebral disc
      herniation and asymptomatic lumbar intervertebral disc herniation). There were
      statistical difference in the width of superior outlet of latero-crypt, anterior
      diastema of flaval ligaments between two groups (symptomatic lumbar
      intervertebral disc herniation and asymptomatic lumbar intervertebral disc
      herniation). (2) There were statistical difference in protrusible
      type,protrusible segment between two groups (symptomatic lumbar intervertebral
      disc herniation and asymptomatic lumbar intervertebral disc herniation).
      CONCLUSION: There were not necessary relationship between in protrusible size,
      location, type, compression degree and clinical symptom. This paper may support
      the mechanism of lumbar intervertebral dise herniation that associated with the
      following the three aspects: (1) spinal reserve capacity (SRC); (2) involved
      nerve roots escaping from herniated disc compression and its elastic lengthening
      function; (3) hypoxia symptosis and anti-ischemia injury compensation of involved
      nerve roots.

PMID- 19408759
TI  - [Report of 5 cases for reconstruction of the complex tissue defect of internal
      and external malleolus in children].

PMID- 19408760
TI  - [Surgical treatment for lumbar intervertebral disc herniation and nerve injury of
      cauda equina].

PMID- 19408761
TI  - [Spiral CT reconstruction for typing of tibial plateau fracture to guide surgical
      therapy].
AB  - OBJECTIVE: To typing of tibial plateau fracture based on spiral CT reconstruction
      and to explore effect of the typing method for treatment. METHODS: A hundred and
      twenty-six cases with tibial plateau fracture (male 95, female 31, age from 23 to
      58 years old), the fractures were classified based on reconstruction image of
      spiral CT. Including central compression type in 13 cases, split type in 8, split
      compression type in 79, comminution type in 26. According to the different typing
      the suitable incision of operation and fixed method for fracture were select.
      RESULTS: A hundred and twenty-six cases were followed up for 0.5-4 years with an
      average of 1.2 years. According to Hohl system score to knee joint function,
      there were statistical significance in the pain,active movement,active range of
      motion between before and after operation (P < 0.01) and there were no
      statistical significance in stability and self-evaluation (P < 0.01). CONCLUSION:
      Typing of tibial plateau fracture based on spiral CT reconstruction helpful to
      choose operative approach, reduction and fixed method and obviously improve
      clinical effect.

PMID- 19408762
TI  - [The selection of responsible veterbal body in PKP (percutaneous kyphosis plasty)
      for aged osteoporotic spinal multiple fracture].
AB  - OBJECTIVE: Through an analysis of the effect of PKP (percutaneous kyphosis
      plasty) for aged osteoporotic spinal multiple fracture to demonstrate the
      importance of the selection of responsible veterbal body. METHODS: Twenty-four
      consecutive procedures were performed in 19 aged patients with osteoporotic
      spinal compression fractures from May 2004 to October 2007. The 24 responsible
      veterbal bodies were confirmed by the manifestations of MRI, X-ray, physical
      examination before the procedures. Established work path through hibateral
      vertebral arch, put into saccule, poured in bone cement under X-ray perspective.
      To observe the condition about symptom improving, fractured reduction and
      complications after operation. RESULTS: The operations were successfully
      completed and the pain released obviously at 2 days after operation. The patients
      can walk next day after operation and no complication found. The mean loss
      percent of the anterior and middle vertebal heights were respectively (34.22 +/-
      11.51)% and (26.53 +/- 11.61)% before operation,postoperative were respectively
      (13.21 +/- 11.43)% and (15.10 +/- 6.50)%. The mean kyphosis corrected from (24.50
      +/- 3.10) degrees to (8.70 +/- 4.30) degrees; the VAS scores decreased from 83.00
      +/- 6.00 to 27.00 +/- 5.00. There was significant difference between before and
      after operation (P < 0.01). CONCLUSIONS: PKP for aged osteoporotic spinal
      multiple fractures by selecting true veterbal body has satisfactory clinical
      efficacy. We should emphasize the importance of the selectivity of responsible
      veterbal body in the procedures. It needs three essential elements: (1) Obviously
      spinous process tenderness and rap pain. (2) X-rays showed veterbal body
      compression fracture; MR showed low signal in veterbal body by T1WI, and high
      signal by T2WI, STIR. (3) The manifestation of radiology can be explained clearly
      by clinical symptomes arid signs.

PMID- 19408764
TI  - [Application of allograft of cortical bone plates in femoral revision with severe
      bone defects].

PMID- 19408763
TI  - [Suture menisci with epidural transfixion pin to treating acute meniscus tear
      under arthroscope].
AB  - OBJECTIVE: To study the utility and effect of suturing menisci with epidural
      transfixion pin to treating acute meniscus tear under arthroscope. METHODS:
      Twenty-two cases with acute meniscus tear were selected, in which 18 were male
      and 4 were female,aged from 17 to 42 years with average of 28.5. The tearing
      menisci were sutured with epidural transfixion pin and unabsorbed suture. The
      follow-up were 6-12 months after operation. Meanwhile, Lysholm score, subjective
      symptoms and examination were recorded. RESULTS: Preoperative Lysholm scores were
      46.72 +/- 13.46, whereas, postoperative ones were 89.43 +/- 18.21. There was
      significant difference between before and after operation (t = 1.85, P < 0.01).
      No recurrent interlocking, no pain in joint medialis and post-medialis space.
      McMurray test was negative. The complications about injury of blood vessel,
      nerves and tendons were not found during 6-12 months follow-up. CONCLUSION: The
      technique is advantageous in convenience, reliability, large suture strength and
      definite curative effect.

PMID- 19408765
TI  - [Endoscopic surgical procedures for the treatment of multi-segment lumbar
      intervertebral disc herniation with posterior approach].

PMID- 19408766
TI  - [Bone transplantation of postlateral-facet joint combined with pedicle screw
      internal fixation in treating lumbar vertebral instability].

PMID- 19408767
TI  - [Analysis of curative effect and choice of therapeutic method for Pilon fracture
      of tibia].

PMID- 19408768
TI  - [Diagnosis and treatment of medial malleolus fracture associated with fracture of
      tibial anterior lip in 7 cases].

PMID- 19408769
TI  - [Application of dynamic external fixator in treating distal radial fractures with
      osteoporosis].

PMID- 19408770
TI  - [The primary report of the clinical application of arthroscopic treatment for
      ankle soft tissue impingement syndrome].

PMID- 19408771
TI  - [Percutaneous fixation for the treatment of fracture of pelvic ring].

PMID- 19408772
TI  - [Fixation with biodegradable screws for treating the fracture and dislocation of
      talus in 16 patients].

PMID- 19408773
TI  - [Treatment of humeral shaft fractures with retrograde expandable intramedullary
      nailing system].

PMID- 19408774
TI  - [Treatment of sacroiliac joint dislocation with bone setting manipulation].

PMID- 19408775
TI  - [Treatment of Colles fracture with manipulation of angulation].

PMID- 19408776
TI  - [Immunologic theory investigation and discussion of pain caused by lumbar
      intervertebral disc herniation (LDH)].
AB  - To explore the main clinical manifestation (lower back pain and ischialgia) of
      LDH with immunologic method and study the relationship and clinical significance
      of the cardinal symptom (pain) and immune comple (IC), macrophage
      (MP),interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF),
      prostaglandin E2 (PGE2), phosphatidase A2 (PLA2), nitrogen monoxidum (NO)
      expressing, finding a new way in order to prevention and cure of LDH. We will
      review immunologic theory of LDH pain.

PMID- 19408777
TI  - [Gluteal fascia compartment sydrome: a report of 2 cases].

PMID- 19408778
TI  - [Progressing study in treating discogenic low back pain].
AB  - Lumbago is a general, frequently and complicated clinical symptom. 60% to 80% in
      adults suffer from back pain of varying degrees. The pain causing by various
      pathological changes stimulateing the ache receptor in intervertebral disc is
      call discogenic low back pain. Along with people knowing more and more about this
      disease, all kinds of treatment techniques are applied in clinic. But the
      indication and therapeutic effects are both evidently different. Below is a
      summary of the therapic method about discogenic low back pain based on
      international and domestic reference data of recent years and the author's
      clinical experiences.

PMID- 19408779
TI  - [Antibiotic prophylaxis for infectious endocarditis: who needs it and when to
      recommend it].

PMID- 19408780
TI  - [Postpartum hemorrhage: an observational study of 21,726 deliveries in 28
      months].
AB  - OBJECTIVE: To describe the management of severe postpartum hemorrhage. MATERIAL
      AND METHODS: Prospective observational study from July 2005 to November 2007 in
      women who were admitted to the recovery unit of a tertiary referral hospital due
      to postpartum hemorrhage. We analyzed incidence, prevalence, morbidity,
      mortality, and associated risk factors. RESULTS: The study included 21,726
      deliveries (124 with severe bleeding). Postpartum hemorrhage was more common
      after an instrumental delivery (odds ratio [OR], 4.54) and after a cesarean
      delivery (OR, 2.86). The risk factors identified in the study population were
      multiple gestation pregnancy and fetal death. One patient died due to
      disseminated intravascular coagulation. The main causes of bleeding were uterine
      atony (45.2%) followed by vaginal tearing (26.6%). Treatment was provided using
      packed red blood cells in 96.8% of the patients, fibrinogen in 49.2%, prothrombin
      complex in 7.25% and activated factor VII in 3.2%. Selective arterial
      embolization was performed in 10.5% of the cases (success rate, 84.6%) and
      hysterectomy was required in 13.7%. The main complications were need for
      postoperative mechanical ventilation (11.3%), myocardial ischemia (4%), pulmonary
      edema (4.8%), acute renal failure (8.9%), ventricular fibrillation (0.8%), and
      death (0.8%). CONCLUSIONS: The incidence of severe postpartum hemorrhage in
      patients treated at our hospital is low, as is the mortality rate. Use of
      fibrinogen is common and provides good results. Angiographic embolization is very
      effective, though the percentage of hysterectomies is still high. Multiple
      gestation pregnancy and fetal death are associated risk factors.

PMID- 19408781
TI  - [Anesthesia nurses' self-assessment of competence].
AB  - OBJECTIVES: The aim of this study was to assess nurses' perceptions of their
      level of competence in their work in the department of anesthesiology, recovery
      care, and pain management. A second objective was to establish a training
      strategy after possibly detecting subjectively perceived needs in different areas
      of competence. MATERIAL AND METHODS: In 2007, 25 nurses belonging to the
      department of anesthesiology, recovery care, and pain management responded to a
      questionnaire based on the hospital's professional development plan. The
      questionnaire included items listing activities performed by anesthesia nurses in
      various areas of competence (patient relations and communication, health
      education, nursing process, task delegation, safety and prevention, team work,
      ethics, teaching and research, administration). RESULTS: A self-assessment of
      "good" or "very good" was recorded by 87.8% of the nurses, while only 6.3%
      evaluated their skills as "sufficient" or "insufficient". The main areas in which
      training was felt to be needed were safety and risk prevention, and teaching and
      research. CONCLUSIONS: In self-assessment, the anesthesia nurses in our hospital
      expressed awareness of training needs. The means to correct skill deficits should
      be provided, through training in theory and practice and attendance at continuing
      professional development courses for anesthesia nurses. The nurses' interest in
      further training should be encouraged given the direct effect it has on quality
      of care.

PMID- 19408783
TI  - [Ultrasound guidance in pediatric regional anesthesia].
AB  - Ultrasound imaging is being used to guide pediatric nerve block procedures.
      Difficulties that arise because of the smaller anatomical structures in children
      can be compensated for by the greater aqueous consistency and reduced
      calcification. Given the shorter distance between the surface of the skin and
      nerves, it is advisable to use a linear array transducer working at a high
      frequency (7-10 MHz). Like adults, children benefit when ultrasound guidance is
      used in the performance of neuraxial nerve trunk blocks, particularly of the
      umbilical and ilioinguinal nerves, and in greater measure in spinal blocks.
      Ultrasound guidance enhances efficacy and also affords the important advantage of
      greater safety. The main disadvantages are the cost of equipment and the
      necessary learning curve.

PMID- 19408782
TI  - [Pediatric complex regional pain syndrome affecting an upper limb: 7 cases and a
      brief review of the literature].
AB  - OBJECTIVES: To review the clinical, psychiatric, and social characteristics of
      complex regional pain syndrome in children and adolescents treated in the last 4
      years at our pediatric pain clinic. MATERIAL AND METHODS: We analyzed the
      specialty of the initial treating physician, age, sex, initial diagnosis, pain
      intensity, degree of disability, fear of movement, clinical stage, history of
      trauma, time between onset and diagnosis, psychiatric illness, family support and
      behavior, chronic pain in near relatives, school grades and attendance, treatment
      given at the pediatric pain clinic, recurrences, and course of disease. RESULTS:
      The cases of 7 patients (4 female, 3 male) between the ages of 8 and 15 years
      were analyzed. Four had been referred by the child psychiatry department. The
      initial diagnosis was erroneous in all but 1 case. Pain intensity and associated
      disability were severe in 5 patients and 4 expressed intense fear of moving the
      limb. Five patients had initial stage I disease, 5 had a history of trauma, and 5
      had been previously treated by immobilization of the limb and prescription of
      nonsteroidal anti-inflammatory drugs. The time between onset and diagnosis ranged
      from 2 to 18 months (mean [SD], 6.4 [3.5] months). In most cases psychiatric
      disease and concomitant social disability were present. Treatment prescribed at
      the pediatric pain clinic consisted of a combination of oral medication,
      psychologic and psychiatric counseling, and intensive physiotherapy for all but 2
      children, who required regional nerve blocks. CONCLUSION: The clinical course was
      satisfactory for all but 1 patient, who developed severe disability. Complex
      regional pain syndrome affecting an upper limb is uncommon in children but not
      rare.

PMID- 19408784
TI  - [Anesthesia considerations for deep-brain stimulation in a patient with type-2
      pantothenate kinase deficiency (Hallervorden-Spatz disease)].
AB  - Neurodegeneration associated with pantothenate kinase deficiency is an autosomal
      recessive condition caused by mutations in the pantothenate kinase 2 gene
      (PANK2). Clinical characteristics include progressive motor impairment and
      dementia. Medical treatment is limited and the dystonia tends to be refractory,
      making stereotactic surgery with placement of deep-brain electrodes an option
      that is being adopted with greater frequency in these patients. We report the
      case of a 32-year-old woman with severe dystonia associated with PANK2 protein
      deficiency. The patient was scheduled for stereotactic bilateral placement of
      electrodes in the medial globus pallidus, guided by computed tomography and under
      general anesthesia, to treat the debilitating dystonia and generalized stiffness
      associated with her condition. Anesthesia was maintained with propofol,
      rocuronium and remifentanil in perfusion during the intervention, which was
      uneventful. After the procedure, the patient was transferred to the intensive
      care unit and sedation was provided with remifentanil to allow slow, gradual
      emergence from anesthesia. The patient was discharged from hospital after
      placement of the implanted pulse generator, and subsequent follow-up showed
      improvement of the dystonia.

PMID- 19408785
TI  - [Anesthetic management in a pregnant woman suffering from idiopathic
      thrombocytopenic purpura].
AB  - Idiopathic thrombocytopenic purpura is an autoimmune disorder characterized by a
      low platelet count. Onset usually occurs during adolescence with episodes of
      cutaneous and mucosal bleeding. Thrombocytopenia during pregnancy is associated
      with many diseases, of which idiopathic thrombocytopenic purpura is the most
      common in the first trimester. The need for treatment will depend on the platelet
      count and whether there is bleeding. At the end of pregnancy, however, whether
      delivery is vaginal or by cesarean, more aggressive therapeutic measures are
      required. Anesthetic management in this type of patient will be determined by
      coagulation status and platelet count, and local or regional anesthesia may be
      contraindicated. We report the case of a pregnant woman with idiopathic
      thrombocytopenic purpura who was admitted to the emergency department of our
      hospital with suspected preeclampsia.

PMID- 19408787
TI  - [Type A hemophilia in a man undergoing liver resection for metastasis:
      implications for anesthetic management].

PMID- 19408786
TI  - [Subdural spinal hematoma and intraventricular bleeding after lumbar puncture].

PMID- 19408788
TI  - [Anesthesia in a patient with homocystinuria and severe pulmonary embolism].

PMID- 19408789
TI  - [Endovascular treatment of a ruptured abdominal aorta aneurysm with local
      anesthesia, sedation and analgesia].

PMID- 19408790
TI  - [General anesthesia with a laryngeal mask in a patient with long-standing Charcot
      Marie-Tooth disease].

PMID- 19408791
TI  - [Obturator nerve lesion after a vaginal delivery without instrumentation under
      epidural analgesia].

PMID- 19408792
TI  - [Ultrasound-guided femoral nerve block: catheter insertion in a girl with
      skeletal abnormalities].

PMID- 19408793
TI  - [General anesthesia with a laryngeal mask in a man with multiple sclerosis].

PMID- 19408794
TI  - [Accidental injection of a water-soluble contrast medium after placement of an
      enteral feeding tube].

PMID- 19408795
TI  - Time to wind back the clock?

PMID- 19408797
TI  - The impact of pre-operative assessment clinics on elective surgical case
      cancellations.
AB  - Pre-operative assessment clinics prepare patients for elective procedures. Little
      is known about their impact on elective case cancellations. We investigated
      whether a pre-operative assessment clinic would reduce surgical case
      cancellations. A retrospective review of all surgical cases over a one year
      period prior to and subsequent to establishment of the clinic was performed. Case
      cancellations during both periods were compared. Statistical analysis was
      performed using the chi-square test. There was a 12.7% increase in the number of
      elective adult procedures performed following establishment of the POAC (815 vs.
      723), although this was not significant (p > 0.05). Pre-assessment resulted in a
      significant reduction in case cancellations (114 vs. 256, p < 0.001). When we
      analysed the data in terms of the reason for cancellation, we found that
      cancellations for medical, but not patient reasons were significantly reduced
      following pre-assessment (p = 0.013 and p = 0.180, respectively). The data
      suggest that establishment ofa pre-operative assessment clinic reduces elective
      case cancellations. In particular we found a significant reduction in
      cancellations for medical reasons.

PMID- 19408796
TI  - Recurrence after inguinal hernia repair at ten years by open darn, open mesh and
      TEP--no advantage with mesh.
AB  - BACKGROUND: Whilst mesh repair is now standard in inguinal hernia surgery, with
      the expectation of a reduction in recurrence rate, the incidence of recurrent
      hernias shows little evidence of decline. Long-term follow-up studies after
      hernia surgery are few. METHODS: 1361 patients underwent 1473 inguinal hernia
      repairs by open mesh, open sutured or total extraperitoneal (TEP) techniques with
      more than ten years' follow-up. FINDINGS: Recurrence rates after open mesh and
      open sutured repair were similar. There has been no benefit in terms of declining
      recurrence from the increasing use of mesh. There was a high rate of early
      recurrence after TEP due to learning curve effects. Late recurrence, occurring
      after two years was uncommon with all techniques, but was lowest after TEP,
      double the rate after open mesh and four times the rate after sutured repair.
      This may be due to mesh protecting the area of muscle weakness' with larger
      meshes conferring a greater long-term benefit. CONCLUSION: Our findings help to
      explain why there has been no significant fall in the incidence of recurrent
      inguinal hernias in national data sets and large scale audits, despite a
      widespread use of mesh.

PMID- 19408798
TI  - The necessity of routine post-thoracostomy tube chest radiographs in post
      operative thoracic surgery patients.
AB  - BACKGROUND: Chest radiographs are routinely performed post-operatively in
      thoracic surgery patients, in particular after the removal of thoracostomy tubes.
      From observation of our practice, we hypothesised that chest radiographs did not
      need to be performed routinely post-operatively and after removal of thoracostomy
      tubes. AIM: To determine whether routine chest radiographs post-operatively and
      post-thoracostomy tube removal directly influenced patient management. MATERIALS
      AND METHODS: A five month prospective study was carried out to analyse our
      current practice at the Thoracic Surgery Unit, Bristol Royal Infirmary, Bristol,
      U.K. Demographic and clinico-pathological data were collected during admission.
      RESULTS: In the cohort of 74 patients, 66 (89%) patients had post-operative chest
      radiographs. Only three (5%) patients who had a chest radiograph had change in
      their management. Twenty-five (34%) patients had a chest radiograph post
      thoracostomy tube removal. Only one (4%) patient in this group who had a chest
      radiograph after thoracostomy tube removal had a change of management.
      Interestingly, the decision to change patient management was not made on the
      basis of the chest radiographs alone; the clinical situation was the main
      determinant. Patients that did not have a chest radiograph postoperatively (eight
      patients, 11%) and post-thoracostomy tube removal (49 patients, 66%) did not
      suffer any adverse sequelae. CONCLUSION: We feel our data support the hypothesis
      that it is not necessary to perform routine chest radiographs in thoracic surgery
      patients post-operatively and after post-operative thoracostomy tube removal. It
      would be better to monitor these patients clinically and only request chest
      radiographs on the basis of deterioration in recorded observations or clinical
      findings.

PMID- 19408799
TI  - Importance of side marking in ophthalmic surgery.
AB  - BACKGROUND: In 2003 the National Patient Safety Agency (NPSA) advised side
      marking for avoiding errors and reducing incorrect side surgery. This survey
      aimed to ascertain whether or not, these 'best practice' guidelines are currently
      being implemented by ophthalmic surgeons in Scotland and, if not, the reasons for
      this, and also to ascertain surgeons' attitudes towards marking. METHODS: Semi
      structured interviews with ophthalmic surgeons throughout Scotland, either face
      to face or by telephone, on their current practices and attitudes relating to
      preventing wrong side surgery. RESULTS: Non-compliance with side marking was
      described by 48% of the surgeons, which includes both consultants and specialist
      registrars. This survey reveals incomplete implementation of this policy in
      ophthalmic surgery for a number of reasons. The most common was bypassing the
      established multi-step process of checks, which risks an increased likelihood of
      surgical errors. CONCLUSION: Guidelines are not consistently being implemented in
      their entirety by eye surgeons in Scotland. In order to improve compliance and
      improve patient safety, we suggest a risk-stratified approach in side marking
      based on individual patient factors that may encourage wider acceptance, without
      compromising patient safety.

PMID- 19408800
TI  - Metatarsal fractures and sports.
AB  - OBJECTIVES: Metatarsal fractures are commonly sustained during sport but little
      is written about metatarsal fractures in the athletic population. Demographics
      and definitive treatment in patients who sustained metatarsal fractures through
      sport were compared with an overall metatarsal fracture population. MATERIALS AND
      METHODS: We used a prospective cohort study from a teaching hospital fracture
      clinic. Eighteen months of data were coded from presentation with a metatarsal
      fracture. Demographics, metatarsal fracture, participating sport and treatment
      were recorded and analysed. RESULTS: 791 patients presented with metatarsal
      fractures in an 18 month period with 74 metatarsal fractures sustained through
      sport. In the overall cohort group, there were 443 females and 348 males with a
      mean age of 44 (age range 15-91) and in the athletic population there were 6
      females and 68 males with a mean age of 26 (age range 15-62). The majority of the
      metatarsal fractures sustained from sport were from soccer (73%), with the fifth
      metatarsal being the most commonly fractured. The definitive treatment in both
      groups appears to be similar, where the mainstay of treatment is conservative
      with the use of cast or early mobilisation with an elasticated support stocking.
      CONCLUSION: In this cohort approximately 9% of metatarsal fractures were
      sustained through sport, with soccer being the most common sport. Following high
      profile injuries to metatarsals in soccer players, it has been suggested that the
      incidence of these fractures is rising. Thus, it is recommended that a detailed
      prospective study be undertaken to specifically study the incidence, aetiology
      and morbidity of metatarsal fractures in the athletic population.

PMID- 19408801
TI  - Sex and the orthopaedic surgeon: a survey of patient, medical student and male
      orthopaedic surgeon attitudes towards female orthopaedic surgeons.
AB  - OBJECTIVE: To ascertain whether perceived negative attitudes regarding female
      orthopaedic surgeons impact on female medical student career choice of
      orthopaedic surgery and determine to what extent these perceptions hold true
      among orthopaedic surgeons and patients. SUBJECTS AND METHODS: A structured
      questionnaire, distributed to three study cohorts; 311 medical students, 182
      patients and 54 orthopaedic surgeons from two specialist orthopaedic hospitals,
      asked questions pertaining to views regarding female orthopaedic surgeons. Binary
      questions and 5-point Likert scale statements were scored. Analysis was
      undertaken using Fisher's exact test and the trend test for proportions.
      Qualitative responses were categorised into themes and reported. Significance
      levels were set at < or = 0.05. RESULTS: Only 24% of female students would
      consider orthopaedic surgical careers, differing significantly from male students
      (p = < 0.01). The reasons given included disinterest and male domination.
      Significantly greater female students had been exposed to negative attitudes
      regarding female surgeons (p = < 0.01), of which 62% would not consider surgery.
      Most patients (89%) had no sex-preference for orthopaedic surgeon. Seventy-five
      percent believed women are surgically as skilled as men and 4% of the patients
      stated they had more confidence in female orthopaedic surgeons compared to males.
      Fifty-eight percent of the surgeons had never encountered negative attitudes. Of
      those that had, skill and family responsibilities were questioned. All agreed
      there is a place for women in orthopaedic surgical careers and welcomed
      diversity. CONCLUSION: Rumoured negative attitudes regarding female orthopaedic
      surgeons still exist among some orthopaedic surgeons, but not patients,
      influencing the undergraduate teaching experience and ultimate career choice in
      orthopaedic surgery.

PMID- 19408802
TI  - Rationale for cancer prevention strategies in high-risk ulcerative colitis.
AB  - Colorectal cancer (CRC) is the most feared long-term complication in patients
      with ulcerative colitis (UC) and Crohn's colitis. Surveillance by colonoscopy and
      serial biopsy is conducted to identify patients most likely to benefit from
      potentially curative surgery. Within this paradigm, patients with high grade
      dysplasia or early stage CRC typically undergo colectomy, while patients free of
      dysplasia continue within surveillance programmes. However, detection of
      dysplasia in colitis may be difficult. Underdiagnosis and undertreatment of
      dysplasia may be accompanied by 'interval cancers' after apparently negative
      colonoscopy, frustrating the goal of cancer prevention. In the absence of a best
      practice model, surgical decisions for effective cancer prevention and control
      can be aided by greater understanding of cancer biology, in particular the close
      relationship between processes of inflammation and neoplastic change. This review
      will summarise recent knowledge in this area and consider clinical variables of
      disease duration, severity and anti-inflammatory therapy against stepwise events
      of neoplastic transformation. Against this background, indications for
      surveillance and prophylactic colectomy in specific clinical situations will be
      discussed.

PMID- 19408803
TI  - Oesophageal achalasia: an argument for primary surgical management.
AB  - INTRODUCTION: Achalasia is a primary oesophageal motility disorder resulting from
      damage to the ganglion cells of the myenteric plexus. Impaired relaxation of the
      lower oesophageal sphincter and aperistalsis causes its cardinal symptoms of
      dysphagia, chest pain and reflux-type symptoms. Management is somewhat
      controversial, with options including systemic and local pharmacotherapy,
      dilatation and oesophagomyotomy. We review the presentation, investigation and
      management of oesophageal achalasia and make an argument for primary surgical
      management. METHODS: We performed a Medline search of the term 'achalasia',
      limiting the search to clinical trials and meta-analyses. We then selected
      articles based on their abstracts using four main criteria: previously unreported
      findings, previously unreported techniques, size of patient cohort and journal
      impact factor. References in selected articles were manually searched for other
      relevant articles. FINDINGS: Achalasia has been managed using a variety of
      techniques including systemic and local pharmacotherapy, forced dilatation and
      oesophagomyotomy. Success rates vary widely between techniques. Mechanical
      disruption ofthe lower oesophageal sphincter is most successful. DISCUSSION: In
      achalasia, mechanical disruption of the lower oesophageal sphincter using forced
      dilatation or surgical myotomy offers the only realistic prospect of long-term
      symptom relief. Recent evidence suggests that previous medical treatment or
      dilatation makes oesophagomyotomy more difficult and increases the risk of
      complications. As the morbidity associated with surgery continues to decrease
      with improvements in minimal access techniques, the argument for primary
      management of achalasia with oesophagomyotomy becomes more compelling.

PMID- 19408804
TI  - Current concepts in gynaecomastia.
AB  - Gynaecomastia is a common breast condition. Each case merits a careful and
      complete history, with thorough examination and investigations being required in
      selected patients with progressive disease or suspected sinister pathology.
      Treatment is usually indicated for any underlying cause, associated symptoms and
      the gynaecomastia itself. Treatment may be either medical or surgical but must be
      individualised. Medical treatment may be especially advocated in the symptomatic
      group. The indications for surgery include failure of medical treatment,
      intolerable side-effects of necessary drugs, malignancy, small lesions which
      cause significant distress and patients with large and ptotic gynaecomastia. A
      careful programme of counselling, pre-operatively in particular, may help to
      minimise litigation.

PMID- 19408805
TI  - Understanding breast cancer-related lymphoedema.
AB  - Breast cancer-related lymphoedema (BCRL) is a chronic swelling of the upper limb
      following surgery to axillary lymph nodes. This clinical literature review
      considers the risk factors that have been identified for the development of BCRL:
      the extent of surgery to the breast and the axilla, radiotherapy, nodal status,
      infection and patient characteristics such as BMI and patient age. The management
      of BCRL is primarily conservative, but the evidence for pharmacological and
      surgical approaches is also considered.

PMID- 19408806
TI  - Transanal endoscopic microsurgery: a novel technique for the repair of benign
      rectovaginal fistula.

PMID- 19408807
TI  - Re: Johnson R D, Stacey R J. The impact of new imaging technologies in
      neurosurgery. Surgeon 2008; 6(6): 344-49.

PMID- 19408808
TI  - Streptococcal myositis a surgical emergency.

PMID- 19408809
TI  - Bisphosphonates in periodontal treatment: a review.
AB  - Periodontitis is a multifactorial disease involving bacterial biofilms and the
      generation of an inflammatory response. The latter causes the major part of the
      periodontal tissue breakdown. Alveolar bone resorption is a major component of
      the periodontal destruction observed in periodontitis. Novel treatment modalities
      of periodontitis intend to control and modulate the host response to bacterial
      aggression. Drugs such as bisphosphonates (BPs) are proven antiresorptive agents
      that can potentially inhibit the alveolar bone resorption. This review describes
      the potential use of BPs in periodontal treatment and could be said that BPs have
      an in vitro and in vivo capability of reducing bone resorption. Only a few
      studies have been carried out on the improvement of clinical periodontal
      parameters after the administration of BPs. Therefore, the published data are not
      sufficient to establish an evidence-based relevance for the use of these drugs in
      the treatment of periodontal diseases.

PMID- 19408810
TI  - In vitro evaluation of enamel remineralisation by a casein phosphopeptide
      amorphous calcium phosphate paste.
AB  - PURPOSE: The aim of this preliminary in vitro study was to evaluate the effect of
      a casein phosphopeptide and amorphous calcium phosphate (CPP-ACP) paste on
      untreated enamel surfaces that had previously been exposed to an erosive
      challenge. MATERIALS AND METHODS: Over a period of 6 h, enamel samples from five
      fully erupted, caries-free molars were incubated with apple juice and later
      covered with CPP-ACP paste for 15 min. Enamel samples incubated with
      physiological sodium chloride solution or with apple juice alone served as
      controls. The quantitative elementary analysis for calcium and phosphorus in
      various depths ranging from 5 to 50 microm was performed using an electron-probe
      microanalyser. RESULTS: Exposure to apple juice resulted in a loss of minerals
      down to a depth of 30 microm with a mean loss of 13% at 5 microm and 6% at 10
      microm. After treatment with CPP-ACP paste, the mineral loss decreased to a mean
      of 9% at 5 microm and remained at 5% at a depth of 10 microm (not a statistically
      significant difference). At a depth of 20 microm, no further mineral loss was
      recorded. CONCLUSIONS: This study demonstrated that there is a slight gain in the
      mineral contents after the application of a CPP-ACP paste, mainly in the upper
      enamel layer. Within the limitations of this in vitro study, the application of
      CPP-ACP paste may enhance the remineralisation after an erosive challenge and
      thus offer some protection for patients who are at risk for erosion.

PMID- 19408811
TI  - Effect of calcium pre-rinse and fluoride dentifrice on enamel and on dental
      plaque formed in situ.
AB  - PURPOSE: The aim of this in situ double-blind randomised crossover study was to
      investigate the effect of calcium (Ca) pre-rinse on the composition of plaque and
      on enamel prior to the use of fluoride (F) dentifrice. MATERIALS AND METHODS:
      During four phases (14 days each) of this study, 10 volunteers had agreed to wear
      dental appliances containing two healthy bovine enamel blocks. A fresh solution
      containing 20% weight/volume (w/v) sucrose was dripped on the enamel blocks ex
      vivo for 5 min three times a day. Subsequently, the appliances were replaced in
      the mouth, and the volunteers rinsed their mouth with 10 mL of a Ca (150 mmol/L)
      or a placebo rinse (1 min). In sequence, a slurry (1:3 w/v) of F (1030 ppm) or
      placebo dentifrice was dripped onto the blocks ex vivo for 1 min. During this
      time, the volunteers brushed their teeth with the respective dentifrice. The
      appliances were replaced in the mouth, and the volunteers rinsed their mouth with
      water. The plaque formed on the blocks was analysed for F and Ca. The enamel
      demineralisation as well as the incorporation of F on enamel was evaluated by
      cross-sectional microhardness and alkali-soluble F analysis, respectively. Data
      were tested using analysis of variance (P < 0.05). RESULTS: The Ca pre-rinse
      prior to the use of the F dentifrice led to a three- and sixfold increase in the
      plaque F and Ca concentrations, respectively. It also did not have any additive
      effect on the F content on the enamel and the demineralisation of the enamel, in
      comparison with the use of F dentifrice alone. CONCLUSIONS: A Ca lactate rinse
      used prior to the F dentifrice was able to change the mineral content in the
      plaque, but it was unable to prevent enamel demineralisation.

PMID- 19408813
TI  - Perceptions and concerns about dental fluorosis as assessed by tooth surface
      index of fluorosis among high school children in an area of endemic fluorosis-
      Kaiwara.
AB  - PURPOSE: The aim of this study was to assess the perceptions and concerns about
      dental fluorosis among high school children in an area that is endemic to
      fluorosis, and to correlate the children's perceptions of dental fluorosis with
      different scores of tooth surface index of fluorosis. MATERIALS AND METHODS: The
      study was conducted among 155 children affected with fluorosis, aged between 12
      and 16 years, studying in all four high schools of Kaiwara, Karnataka, India.
      Fluorosis was assessed on labial surfaces of maxillary anterior teeth using tooth
      surface index of fluorosis, and the data were collected using a self-administered
      pretested questionnaire that was given to the study subjects. Analysis was
      performed using frequency distribution, chi-square test and Spearman's
      correlation coefficients. RESULTS: Significant high correlations were found
      between tooth surface index of fluorosis scores and the perception of the
      importance of the condition (r = 0.226, chi2 = 72.065, P < 0.01), considering the
      condition to be a disadvantage in the future (r = 0.166, chi2 = 73.097, P < 0.05)
      and also the last visit to the clinician for the condition (r = -0.184, chi2 =
      14.252, P < 0.05). CONCLUSION: Perceptions and concerns of dental fluorosis among
      this age group of children appear to be of aesthetic concern making it essential
      to focus on this issue and to intervene.

PMID- 19408812
TI  - Surface roughness and bacterial adherence to resin composites and ceramics.
AB  - PURPOSE: The aim of this study was to evaluate the surface roughness and the in
      vitro adherence of Streptococcus mutans to indirect aesthetic restorative
      materials that are uncoated with saliva. MATERIALS AND METHODS: Four groups of
      restorative materials were evaluated according to material type: (1)
      microparticulate feldspathic ceramic; (2) leucite-reinforced feldspathic ceramic;
      (3) microhybrid resin composite and (4) microfilled resin composite. Twenty
      standardised samples of each material were produced. Roughness analysis (Ra, n =
      10) was performed using a roughness analyser. Adhesion tests (n = 10) were
      carried out in 24-well plates; colony-forming units (CFU/mL) were evaluated. The
      mean values of roughness (microm) and adherence (CFU/mL) for each group were
      subjected to an analysis of variance and a Tukey test. RESULTS: The leucite
      reinforced feldspathic ceramic was rougher and presented higher bacterial
      adherence than the microparticulate feldspathic ceramic. The resin composites
      were similar with regard to surface roughness and bacterial adherence.
      CONCLUSIONS: The microhybrid and microfilled resin composites were similar and
      the leucite-reinforced feldspathic ceramic was rougher and presented higher
      bacterial adherence than the microparticulate feldspathic ceramic.

PMID- 19408814
TI  - Low maternal schooling and severity of dental caries in Brazilian preschool
      children.
AB  - PURPOSE: The aim of this study was to identify the prevalence and severity of
      caries and of early childhood caries (ECC) in preschool children from the
      municipality of Capivari de Baixo, Brazil. Furthermore, the aim was to ascertain
      the association between these prevalences and the level of maternal schooling.
      MATERIALS AND METHODS: A cross-sectional study was performed involving all
      children aged 3 to 5 years enrolled in all municipal schools of Capivari de
      Baixo, Brazil. The clinical information was obtained using the World Health
      Organization criteria. For ECC, it was observed if the child presented with
      lesions with acute evolution, whitening clinical aspect and softened consistency.
      Non-clinical data were obtained by means of interviews with the child's mothers,
      by investigating the child and through questions relating to the maternal age,
      the maternal level of schooling and the time of weaning. Tests of association
      were performed using the chi-square test followed by unconditional multiple
      logistic regression analysis to test the independence of the association between
      the outcomes and the explanatory variables. RESULTS: The prevalence of caries was
      64.3%, the mean dmft was 1.24 and the prevalence of ECC was 4.9%. A child was
      more likely to present with severe caries (dmft > or = 2) if aged 47 months or
      above. Low maternal schooling made the occurrence of both severe caries and ECC
      more likely. CONCLUSIONS: The population that was studied presented levels of
      oral health better than those found in other Brazilian population groups,
      although groups remain with a high severity of caries associated with low
      maternal schooling.

PMID- 19408815
TI  - Multi-species biofilm formation on dental materials and an adhesive patch.
AB  - PURPOSE: This laboratory study assessed the influence of surface roughness and
      contact time on the formation of a multi-species biofilm on dental materials
      (adhesive patch, composite, amalgam and enamel). MATERIALS AND METHODS: Rough and
      smooth specimens of each material were prepared and the mean surface roughness
      was assessed profilometrically. The biofilms were then allowed to grow either for
      15 min or 15 h respectively on saliva-preconditioned specimens of each material,
      and colony-forming units on blood agar were counted (N = 9/group) Surface
      morphology was assessed using a scanning electron microscope. RESULTS: No
      difference was found in the biofilm formation rate among all the materials that
      were tested. After a short incubation period, a statistical significant
      difference between smooth and rough samples could be detected on amalgam and on
      the resin composite material (P < or = 0.001). CONCLUSIONS: Surface roughness may
      influence the initial biofilm adherence, but differences vanish following growth
      and maturation. The multi-species biofilm offers a reliable laboratory model for
      studying plaque formation.

PMID- 19408816
TI  - Occlusal accommodation and mouthguards for prevention of orofacial trauma.
AB  - PURPOSE: The aim of this study was to investigate the effect of two types of
      occlusal accommodation on the arch separation in centric and eccentric arch
      positions and to assess the opposing tooth contacts in professionally made,
      thermoformed sports mouthguards. MATERIALS AND METHODS: Maxillary and mandibular
      alginate impressions, a wax interocclusal record of centric occlusion together
      with maxillary/condylar face-bow registrations, were recorded clinically for 10
      undergraduate dental students who are sports activist volunteers of the School of
      Medicine and Dentistry, Queen's University Belfast. Two ethylene vinyl acetate
      thermoformed maxillary mouthguards were made for each player (N = 20) using a
      standardised procedure. Ten mouthguards served both as the control (i.e. the non
      accommodated) group and also the accommodated, occlusally 'imprinted' group. The
      other 10 mouthguards served as the accommodated, occlusally 'ground' group. Casts
      were articulated, each non-accommodated and accommodated mouthguard was seated
      and the extent of the interocclusal opening was recorded in all three arch
      relationships. The number of mouthguard and mandibular tooth contacts were also
      recorded in each position. RESULTS: The increased vertical occlusal dimension
      that was found in the presence of non-accommodated mouthguards equated to the
      full-sheet thickness of the material that was used to form the mouthguards. Only
      mouthguards accommodated by grinding retained high levels of occlusal contact in
      all arch relationships that were tested. CONCLUSIONS: Within the limitations of
      this study, the modification of the occlusal surface made by flat grinding
      reduced the arch separation in eccentric movements and increased the opposing
      tooth contacts in custom-made mouthguards. This may contribute to increased
      comfort, compliance and the protective effect of these appliances thus resulting
      in a reduction of injuries to the teeth, arches and soft tissues.

PMID- 19408817
TI  - Lifelong exposure to smoking and oral health among 35- to 44-year-old Iranians.
AB  - PURPOSE: The objective of this study was to assess the periodontal treatment
      needs and the dental status in relation to smoking indicators with special
      emphasis on lifelong exposure to smoking among 35- to 44-year-old Iranian dentate
      subjects. MATERIALS AND METHODS: Data (N = 8276) were collected as part of a
      national survey using the World Health Organization criteria for sampling and for
      using the data as clinical indicators. Gender, age, place of residence and level
      of education served as sociodemographic information, and community periodontal
      index (CPI) and number of teeth served as clinical measurements. The smoking
      indicators comprised smoking, duration of smoking (years), daily smoking
      (cigarettes/day) and lifelong exposure to smoking. RESULTS: In total, 81% of the
      subjects were non-smokers, and 32% of the males and 5% of the females were
      current smokers. Maximal CPI = 2 was found among 40% of the subjects, and 53% had
      maximal CPI > or = 3. Higher periodontal treatment needs were associated with
      smoking (P < 0.01) in males; CPI = 4 was more frequent (P < 0.01) and the mean
      number of teeth was lower (P < 0.01) among groups with higher levels of smoking.
      Heavy smokers were the most likely to have maximal CPI > or = 3 (odds ratios, OR
      = 2.9; 95% confidence intervals, 95% CI = 1.8 to 4.7) and to have < 20 teeth (OR
      = 2.3; 95% CI = 1.5 to 3.6). CONCLUSIONS: Smoking and lifelong exposure to
      smoking with a dose-dependent effect seem to be associated with higher
      periodontal treatment needs and poorer dental status among the middle-aged,
      particularly in males and in low socioeconomic groups in Iran.

PMID- 19408819
TI  - Oral piercing complications among teenage students.
AB  - PURPOSE: The aim of this study was to assess the use of oral piercings and their
      possible associated complications among students aged 14 to 18 years. MATERIALS
      AND METHODS: A total of 927 students from private and state schools were invited
      to participate in this study. The participants were subjected to clinical
      examination, and a questionnaire was provided for collecting the following data:
      gender, piercing location, oral complications or alterations, and cleaning
      frequency. RESULTS: Among the students who were analysed, 33 had oral piercings
      (3.6%); 69.70% were from state schools and 30.30% were from private schools.
      There was a slight predominance of males (54.55%) compared with females (45.45%).
      The tongue was the most common location for piercing (66.6%). The complications
      and alterations associated with the use of piercing were observed in 74.3% of the
      cases. CONCLUSIONS: In the population that was studied, oral piercing was
      observed in a small percentage of teenage students (3.6%) and there were local
      complications associated with its use.

PMID- 19408818
TI  - Delayed diagnosis of oral cancer in Iran: challenge for prevention.
AB  - PURPOSE: The aim of this study was to investigate the diagnostic delay and its
      determinants among oral cancer patients in Tehran, Iran. MATERIALS AND METHODS:
      This study was conducted between September 2004 and September 2006 in three
      university hospitals, and included 100 consecutive patients with primary oral
      squamous cell carcinoma (international classification of disease, ICD-10 sites
      C01 to C06). Data were obtained through questionnaire interviews and medical
      records of the patients were reviewed to obtain information on the date of
      diagnosis, primary tumour site and the stage of the tumour at the time of
      diagnosis. Statistical analysis was performed by t test, ANOVA and logistic
      regression. RESULTS: The mean diagnostic delay was 7.2 months (SD 7.5, range 1 to
      36 and median 4). The most important determinants of longer diagnostic delay were
      being single (OR = 4.8; 95% CI = 1.5 to 14.8; P < 0.05) and being at advanced
      tumour stages (OR = 5.3; 95% CI = 1.8 to 15.6; P < 0.01). The mean patient and
      professional delays were 5.3 months (SD 6.1 and median 2) and 2.1 months (SD 2.1
      and median 1), respectively. Patients at advanced tumour stages were more likely
      to have longer patient and professional delays than those at early stages (OR =
      5.6; 95% CI = 1.8 to 17.3 and OR = 3.4; 95% CI = 1.2 to 9.4, respectively; P <
      0.05). Living alone was also a determinant of longer patient and professional
      delays (OR = 7.1; 95% CI = 2.0 to 24.7, OR = 3.5; 95% CI = 1.2 to 10.3,
      respectively; P < 0.05). CONCLUSIONS: Developing preventive programmes that focus
      on the enhancement of public and professional awareness about oral cancer is
      essential to promote earlier diagnosis in Iran.

PMID- 19408820
TI  - Occlusion and orthodontic treatment demand among Chinese young adults in Hong
      Kong.
AB  - PURPOSE: The aim of this study was to investigate the occlusion, the demand for
      orthodontic treatment and the reasons for this among Chinese young adults in Hong
      Kong. MATERIALS AND METHODS: A questionnaire was used to study previous
      orthodontic experience and to evaluate the orthodontic treatment demand and the
      reasons for this in Chinese university students. Among those who had no
      orthodontic treatment, 120 participants were invited for an occlusal assessment.
      Their treatment need was graded using the index of orthodontic treatment need.
      RESULTS: A total of 240 students, aged 18 to 27 years, completed the
      questionnaire survey. Thirty-one students (13%) had orthodontic treatment. Sixty
      seven (28%) students had orthodontic treatment demand, and their common reasons
      were to improve appearance (78%), self-image (36%), self-confidence (34%) as well
      as to follow parental advice (24%). The reasons for those students who would not
      consider having orthodontic treatment included no perceived need (64%), long
      treatment time (18%) and high treatment fee (14%). All 120 invited participants
      who had no orthodontic treatment attended the occlusal assessment. One-fifth had
      a normal occlusion. Most malocclusions were manifested as Angle Class I (48%)
      followed by Class III (21%) malocclusion. Fifty-six students (47%) had moderate
      and 40 students (33%) had 'great' or 'extremely great' treatment need.
      CONCLUSIONS: The most prevalent malocclusion among this group of Chinese young
      adults was Angle Class I malocclusion. Although the majority of the Chinese young
      adults had malocclusion with a high treatment need, their demand for orthodontic
      treatment was relatively low. Apart from consideration of dental health needs,
      the common reasons for orthodontic treatment demand were influenced by the desire
      for improvement in appearance.

PMID- 19408821
TI  - Individual versus group oral hygiene instruction for adults.
AB  - PURPOSE: The objective of this study was to assess the practicability and
      effectiveness of group oral hygiene instruction for adults in comparison with
      individual oral hygiene instruction. MATERIALS AND METHODS: A total of 104 male
      subjects aged 18 to 54 (mean age: 29.7) years were randomly assigned to one of
      four groups: group A was given individual oral hygiene instruction; group B was
      given group oral hygiene instruction; group C was given a combination of
      individual and group oral hygiene instructions; and group D received no oral
      hygiene instruction (the control group). The success of each form of instruction
      was evaluated on the basis of four parameters: (1) the Quigley-Hein plaque index
      (QHI), (2) the approximal plaque index (API), (3) a modified sulcus bleeding
      index (SBI) and (4) the community periodontal index of treatment needs (CPITN).
      All participants had professional tooth cleaning at the end of the baseline
      examination. The final examinations were conducted 13 weeks later. RESULTS: All
      subjects showed a poor oral health status at the beginning of the study, and the
      mean QHI score was 2.2. In addition, 92% of all subjects had an API score of more
      than 70%. Moderate-to-severe gingival inflammation (modified SBI) was observed in
      67.3% of the subjects. CPITN scores of 2 or 3 were calculated for 82% of all
      sextants. At the end of the study, all groups showed a significant improvement in
      their oral health status and periodontal parameters (P < 0.0001). The majority of
      the subjects achieved an API score between 25% and 70%, and they had a mean QHI
      score of 1.2. A CPITN score of 0 or 1 was recorded for most sextants (62%). There
      was no significant difference between the various groups. CONCLUSIONS: This study
      demonstrated that group oral hygiene instruction and conventional individual
      instruction have similar beneficial effects in adults.

PMID- 19408822
TI  - The effects of heparin on DLD-1 colon cancer cell line.
AB  - BACKGROUND: Patients with cancer are frequently treated with anticoagulants,
      including heparin, to prevent or to treat the deep vein thrombosis. It has been
      indicated that heparin affects the survival of patients with cancer. Also, the
      apoptotic and antiproliferative effects of heparin on some cancers has been
      demonstrated. Experimental studies support the hypothesis that cancer progression
      can be influenced by heparin, but the results of these studies are not
      conclusive. OBJECTIVES: We planned to investigate the effects of different
      concentrations of heparin in the colon cancer cell line DLD-1. METHODS: This
      study was done by the addition of heparin in different doses into colon cancer
      cell line DLD-1 in vitro. After an incubation period of 72 hours, study and
      control groups were evaluated for viable cell count, percentage of proliferating
      index and apopitosis percentage. RESULTS: The result of the viable cell count in
      the second and third study groups (98.35+/-27.3, 97.23+/-39.38) were low compared
      to the control group. The results of the proliferative index of study groups
      (46.47+/-10.44, 47.23+/-12.03, 45.55+/-14.2) were higher than the control group
      (40.62+/-9.28). The results of apoptosis in study groups (14.35+/-1.93, 16.47+/
      7.25, 13.56+/-5.66) were lower compared to the control group (22.17+/-15.9). But
      these results were not statistically significant. CONCLUSION: Heparin has no
      significant anti-proliferative and apoptotic effects on colon cancer cells in
      vitro. Therefore, for clinical applications, more advanced studies are needed to
      examine the effect of heparin on colon cancer (Tab. 3, Fig. 3, Ref. 25). Full
      Text (Free, PDF) www.bmj.sk.

PMID- 19408823
TI  - Distribution of the 22 cytokine gene polymorphisms in healthy Macedonian
      population.
AB  - BACKGROUND: Distribution of cytokine gene polymorphisms may vary significantly
      among different ethnic groups, and eventually contribute to observed differences
      in disease frequencies. OBJECTIVES: To genotype 22 cytokine polymorphisms in the
      Macedonian population. The Macedonian population consists of 301 healthy
      unrelated individuals. METHODS: Blood samples were collected after written
      consent, DNA was isolated from peripheral blood, and 22 polymorphisms were typed:
      IL-1alpha -889, IL-1beta -511, IL-1beta +3962, IL-1R psti1970, IL-1RN mspa11100,
      IL-4Ralpha +1902, IL-12 -1188, IFNgamma utr5644, TGF-beta1 cdn10, TGF-beta1
      cdn25, TNF-alpha -308, TNF-alpha -238, IL-2 -330, IL-2 +166, IL-4 -1098, IL-4 
      590, IL-4 -33, IL-6 -174, IL-6 565, IL-10 -1082, IL-10 -819, and IL-10 -592.
      Cytokine genotyping was performed by PCR-SSP (Heidelberg kit). The population
      genetics analysis package, PyPop, was used for analysis of the cytokine data.
      RESULTS: Test of neutrality (Fnd) showed negative value, but was significantly
      different from 0 for TGF-beta1 1 cdn10 and IFNgamma utr5644 (p of F = 0.001, and
      0.012 respectively). Several SNPs (IL-1alpha -889, IL-1beta +3962, IL-2 + 166, IL
      4 -1098, IL-4 -590, IL-4 -33, and IL-10 -592) were not in HWP (p 0.005). Test of
      neutrality for cytokine haplotypes (TGF-beta1, TNFalpha, IL-2, IL-4, IL-6, and IL
      10) showed significantly difference from 0 only for IL-2 haplotypes (p=0.020).
      CONCLUSION: The results of cytokine polymorphisms in Macedonian population can be
      used for anthropological comparisons, as well as for association studies with
      different diseases (Tab. 6, Ref. 34). Full Text (Free, PDF) www. bmj. sk.

PMID- 19408824
TI  - Laboratory testing of hereditary thrombophilia: previous data in the face of
      verification.
AB  - OBJECTIVE: Mutations in hemocoagulation factors genes are nowadays routinely
      examined parameters, important in hereditary trombophilia determination. We have
      complexly evaluated laboratory data from the 211 unselected patients with venous
      thrombosis, and compared with the former studies in the same Slovakian
      population. RESULTS: The Factor V Leiden mutation (FVL) was found in 43 of 211
      patients (20.38%), with the mutant allele frequency=10.2%, while the prothrombine
      G20210A mutation was revealed in 11/205 individuals (5.37%), with the mutant PT
      20210A allele frequency=2.68%. In both mutations, all carriers of mutant allele
      were heterozygotes. In 81 individuals was examined the PCAT-NR with the ProC
      Global assay. Of them, 24 was heterozygotes for FVL mutation with considerably
      lower PCAT-NR levels (median=0.67; range: 0.53-0.83) compared with homozygotes
      without FVL mutation (n=57; median=0.84; range: 0.54-1.67; p<0.001). The
      sensitivity of the assay was 0.88 (95% CI: 0.68-0.97) and the specifity =0.67
      (95% CI: 0.53-0.79). CONCLUSIONS: Our examination revealed considerably lower
      frequency of the FVL mutation in the target population, by contrast to the
      neighbouring Caucasian populations. As for the PT 20210 mutation, the differences
      are milder. Even though the PCAT-NR was validly sensitive (sensitivity=0.88, 95%
      CI: 0.68-0.97) to the FVL mutation, only DNA-testing is the definitive assay for
      FVL-carriership (Ref. 19). Full Text (Free, PDF) www.bmj.sk.

PMID- 19408825
TI  - Plasma hyaluronidase activity as an indicator of atherosclerosis in patients with
      coronary artery disease.
AB  - BACKGROUND AND OBJECTIVE: Recent information has highlightened the impact of HA
      metabolism alterations in vascular permeability through its actions on
      endothelial glycocalyx and the importance of HA-cell interactions in cell
      behavior of arterial endothelial and smooth muscle cells. Therefore hyaluronan is
      thought to involve in pathophysiology of atherosclerosis. The aim of this study
      is to investigate the association of plasma hyaluronidase activity with
      atherosclerosis in non-diabetic patients with stable coronary artery disease.
      METHODS: In the present study we used plasma hyaluronidase measurement as an
      indicator of hyaluronan metabolism and activity. A total of 162 subjects
      undergoing to coronary angiography were divided into two groups according to
      presence or absence of coronary artery disease, and their serum hyaluronidase
      activity were measured. RESULTS: Serum hyaluronidase activities were 3797+/
      670.62 mU/L and 2838+/-417.67 mU/L for patients with CAD (n:109) and control
      patients without CAD (n:53), respectively. Serum hyaluronidase activity in
      patients with coronary artery disease (CAD) were significantly higher than
      control subjects without CAD (p<0.001). CONCLUSION: In the present study
      hyaluronidase activity was found to be associated with coronary artery disease
      reflecting the role of hyaluronan in atherosclerosis. We believe that the
      demonstration of relationship between serum hyaluronidase activity and
      atherosclerosis represents a remarkable finding highlighting the potential role
      of hyaluronan in pathophysiology of atherosclerosis (Tab. 2, Fig. 3, Ref. 28).
      Full Text (Free, PDF) www.bmj.sk.

PMID- 19408826
TI  - Analysis of surgical complications of thyroid diseases: results of a single
      institution.
AB  - BACKGROUND: The purpose of this study is to compare the complications of
      different types of thyroidectomy for benign and malignant thyroidal diseases.
      METHODS: Between January 2001 and March 2006, 982 patients underwent
      thyroidectomy in single institute. A retrospective analysis was performed on
      demographic characteristics and pathology reports of patients, complications of
      surgery as well as the follow-up of patients. Sixty patients could not be fully
      followed up and were excluded. RESULTS: The types of the surgical procedures were
      as follows; 451 (48.9%) total, 137 (14.9%) subtotal, 60 (6.5%) near-total
      thyroidectomy and 274 (29.8%) lobectomy with isthmectomy. In the benign group,
      temporary recurrent laryngeal nerve injury (RLNI) was the most common
      complication in patients with toxic diffuse goiter (TDG 2%) while this
      complication occurred in patients with differentiated thyroid cancer (DTC 1.5%)
      in the malign group. Permanent RLNI in benign thyroidal diseases was seen more
      commonly in patients with toxic multinodular goiter (1.3%). In benign thyroidal
      diseases, temporary hypoparathyroidism (THPT) was mostly found in patients with
      TDG (8%), whereas in malignant thyroidal diseases this was found more in patients
      with DTC (2%). Permanent HPT (PHPT) in benign thyroidal diseases was observed
      more commonly in patients with multinodular goiter (0.9%). In malignant thyroidal
      diseases, it was more frequently observed in patients with DTC (0.5%). Infective
      complications after thyroid surgery are rarely observed and have a low incidence
      (0.4%). CONCLUSION: RLNI and HPT are the most common complications of after
      thyroid surgery but they may be avoided with an accurate technique (Tab. 3, Ref.
      15). Full Text (Free, PDF) www.bmj.sk.

PMID- 19408827
TI  - Thyroid diseases in children and adolescents.
AB  - BACKGROUND: Thyroid nodules are relatively rare in children and adolescents and
      have a prevalence between 0.2%-1.8%. They are more often malignant in children
      than in adults and thus an early diagnosis is extremely important. OBJECTIVE: The
      aim of the study was to analyze the group of pediatric patients with nodular
      thyroid diseases. METHODS: The authors processed the documentation of 66
      pediatric patients with nodular thyroid disease who have been surgically treated
      at the Clinic of Otorhinolaryngology and Head and Neck Surgery, JFM CU and MFH in
      Martin during 2003-2007. RESULTS: Family history was positive in 32 patients
      (48.5%). Twenty-three patients (35%) had hyperfunction thyroid disease. Euthyroid
      status was found in 43 patients (65%). Ultrasonography examination was performed
      in all patients. Percutaneous aspiration biopsy was performed in 38 patients
      (58%) and peroperative histology in 40 patients (61%). Technecium (Tc)99m
      scintigraphy was performed in 4 patients (6%). CT and MRI examination of the neck
      and upper mediastinum was indicated in one child. All patients were surgically
      treated with classical approach after achieving euthyroid stage. Total
      thyroidectomy was performed in 24 patients, hemithyroidectomy in 41 patients and
      isthmectomy was done in one patient. No severe postoperative complications were
      present. CONCLUSION: Thyroid diseases are the second most frequent endocrinopathy
      in children and adolescents with girls being more frequently affected. It is
      multidisciplinary problem requiring cooperation of specialists in different
      fields of medicine. In patients with thyroid diseases not responding to
      conservative treatment or with clinical signs of mechanical syndrom surgery is a
      causal therapy (Tab. 3, Ref. 20). Full Text (Free, PDF) www.bmj.sk.

PMID- 19408828
TI  - Surgical interventions in patients with chronic constipation refractory to
      intensive medical treatment.
AB  - INTRODUCTION: Management of patients with chronic constipation (CC), irresponsive
      to medical treatment, is very difficult. There are some surgical approaches
      reported for the treatment. In this study we aimed to assess the results of
      different surgical procedures in patients with severe CC who were refractory to
      intensive medical treatments. METHODS: Fifteen patients with refractory chronic
      constipation underwent surgical management between 1998 and 2003 in Ankara
      University School of Medicine Department of General Surgery. RESULTS: Median age
      of the patients was 40 years (range, 24-77), female/male ratio was 11/4, median
      duration of symptoms was 13 years (range, 4-35 years) and median interval of two
      subsequent bowel movements was 15 (range, 5-30) days. Preoperative evaluation
      including barium enema, colonoscopy, colonic transit time, and cinedefecography
      and balloon expulsion test were done in all patients. Clinical analysis of
      constipation with these tests indicated a simple slow transit colon in three
      patients but more complicated variations of combined anatomical functional
      disorders in the rest of the cases. Surgical procedures consisted of total
      colectomy, Frykman-Goldberg procedure, Wells procedure and appendisostomy,
      laparoscopically in 8 of them. Deep vein thrombosis developed in the
      postoperative period after rectopexy and pelvic floor repair in one case. The
      median follow-up time was 5.5 years. Fourteen (93.3%) patients had an excellent
      bowel movement and were highly satisfied with the surgical management.
      CONCLUSION: Surgical interventions may be beneficial in selected patients with
      refractory chronic constipation (Tab. 2, Ref. 13). Full Text (Free, PDF)
      www.bmj.sk.

PMID- 19408829
TI  - Osteoplastic static thumb replacement for the total traumatic thumb loss.
AB  - Despite the fact that replantation of the thumb is at present a common procedure,
      occasionally due to the different reasons replantation is unsuccessful. We
      present a case where we have to cope with complete thenar loss and following
      reconstruction was done in an unusual way. Primarily we have covered the thenar
      defect with inguinal flap and secondarily we have made thumb bone replacement
      with heterogenous bone block fixed to the second metacarpal bone. We would like
      to point out that sometimes it is necessary to make reconstructions by unusual
      way (Fig. 7, Ref. 14). Full Text (Free, PDF) www.bmj.sk.

PMID- 19408830
TI  - A single-surgeon, single-institute experience of 115 Lichtenstein hernia repairs
      under local anesthesia.
AB  - BACKGROUND: Repair of an inguinal hernia is one of the most common operations
      performed in general surgery with significant costs to health care and society.
      Lichtenstein mesh repair has been the most widely performed groin hernia repair.
      In this study, we wanted to emphasize the effectiveness of local anesthesia in
      groin hernia repair by single-surgeon's experience. METHODS: One-hundred and
      fifteen inguinal hernia patients were reviewed between July 2005 and July 2007.
      2% Prilocaine was injected for local anesthesia and Lichtenstein polypropylene
      mesh repair technique was performed. Pain was assessed after operation by using a
      visual analogue scale (VAS). All patients were controlled at postoperative first
      week, first month and end of first year. RESULTS: 113 (98.26%) of 115 patients
      were discharged at postoperative 8th hour. The other 2 patients (1.739%) were
      discharged at postoperative second day. They were followed up two days, because
      of seroma and pain, individually. Mean VAS score was 3.2 (2.7-4.0 95% CI). There
      was no statistically significant difference between groups, according to Nyhus
      classification, right/left inguinal hernia and gender. CONCLUSION: Lichtenstein
      mesh repair under local anesthesia is an effective day case technique,
      particularly in the elderly and medically unfit patients. The economic benefits
      are enhanced by low morbidity and low recurrence rates (Ref. 5). Full Text (Free,
      PDF) www.bmj.sk.

PMID- 19408831
TI  - Low-molecular weight heparin enoxaparin in the treatment of acute coronary
      syndromes without ST segment elevation.
AB  - OBJECTIVES: We compared the incidence of adverse cardiac outcomes of enoxaparin
      vs unfractionated heparin in the management of ACS-NSTE. BACKGROUND: Low
      molecular-weight heparins are the potential new standard in the treatment of
      acute coronary syndromes without ST-segment elevation (ACS-NSTE). The benefit is
      addressed to significant diminution of the adverse clinical events--recurrent
      angina (RA), myocardial infarction (MI), heart failure (HF), cerebrovascular
      insult (ICV), coronary artery by-pass graft (CABG), percutaneous coronary
      intervention (PCI) and death. METHODS: Sixty patients with ACS-NSTE were
      randomised to receive Enoxaparin 1 mg/kg body weight s.c twice daily (n=30) and
      unfractionated heparin (Heparin - "Biochemie" 25.000 IU/5 ml), according to
      Rashke nomogram (n=30). The end point were RA, MI, HF, ICV, CABG, PCI and death
      at day 180. The Kaplan-Meier estimation technique was used to compared the time
      to events for two treatments. A p<0.05 was considered to indicate significance.
      RESULTS: For 180 days, RA, MI, HF, ICV and death were lower in the Enoxaparin vs
      UFH group (36.6% vs 73.3%, p=0.001), (30% vs 53.3%, p=0.05), (13.3% vs 23.3%,
      p=0.31), (3.3% vs 10%, p=0.29), (3.3% vs 10%, p=0.31), respectively. CABG were
      similar 13.3% (p=0.96). PCI were performing in 33.3% in UFH vs 90% in LMWH
      (p=0.0001). CONCLUSION: The use of Enoxaparin in ACS-NSTE schows impressive
      decrease of incidence of ischemic events (Fig. 7, Ref. 8). Full Text (Free, PDF)
      www.bmj.sk.

PMID- 19408832
TI  - The PlasmaKinetic tissue management system in thyroid surgery.
AB  - BACKGROUND: Thyroid surgery involves meticulous devascularization of the gland.
      Although conventional technique being a highly efficient technique for vessel
      bleeding control, it takes long time. The aim of this study was evaluate the
      efficacy of PlasmaKinetic to the conventional technique. METHODS: We reviewed the
      medical records of 86 patients who underwent primary thyroid surgery by the same
      surgeon at our clinic between June 2006 and January 2008. Total thyroidectomy was
      performed at all of the patients in the study group. RESULTS: When the incidence
      of postoperative cord palsy was 2.32%, transient hypoparathyroidism was 4.6%.
      There was no significant difference in consideration of age, gender, thyroid
      gland weight, and complication rates between the PlasmaKinetic group and
      conventional group (p>0.05). Operation time, mean drainage from the suction drain
      and duration of hospital stay of the patients in PlasmaKinetic group were
      significantly lower than those in conventional group (p<0.05). CONCLUSION:
      PlasmaKinetic technique decreases the operation time to a level of less than 50
      minutes with no increase at complication rate (Tab. 3, Fig. 3, Ref. 14). Full
      Text (Free, PDF) www.bmj.sk.

PMID- 19408833
TI  - An epidemiological cross-sectional study of the knowledge of the clinicians on
      surgical ethics of informed consent in emergency patients.
AB  - This was an epidemiological cross-sectional study on the knowledge of the
      clinicians on the surgical ethics especially the informed consent among the
      surgically emergency patients in the various units of the General Surgery
      Department, Chittagong Medical Hospital, Bangladesh which revealed that the
      majority of the graduate clinicians (42.6%) found to have only some hazy ideas
      about informed consent whereas in case of post graduate clinicians only 50% were
      found to have the satisfactory ideas about this, but in general the only 6.3%
      clinicians were found to have excellent and perfect ideas in this relation. A
      majority group (15.9%) was found who had no satisfactory answer followed by 14.3%
      had none of any specific preferable nature of informed consent. About 46.9% of
      the graduate and 28.6% post graduate clinicians were found to have no idea about
      Nuremberg Code, IRB or NMRC. A terrific picture, wasn't it 98 Graduate and 28
      post graduate clinicians were included in this study (Tab. 6, Fig. 4, Ref. 38).
      Full Text (Free, PDF) www.bmj.sk.

PMID- 19408834
TI  - Amebic perforation of small bowel: an unexpected localization of a fatal
      complication.
AB  - The intestinal protozoan parasite E. histolytica is the causative organism
      responsible for human amebiasis and amebic dysentery. Although it is primarily an
      infection of the colon, it may also be spread by hematogenous path to other
      organs, especially the liver. In general, the clinical spectrum of colorectal
      amebiasis ranges from the state of asymptomatic carrier to severe fulminant
      necrotizing colitis with bleeding and perforation. Here we present an extremely
      rare case of necrotizing amebiasis of small bowel with a fatal outcome (Fig. 1,
      Ref. 4). Full Text (Free, PDF) www.bmj.sk.

PMID- 19408836
TI  - Urinary N-acetyl-beta-D-glucosaminidase (U-NAG) activity in children with
      vesicoureteral reflux.
AB  - OBJECTIVES: The aim of this study was to measure U-NAG in children with
      vesicoureteral reflux (VUR) and examine the relationship between selected
      clinical parameters. BACKGROUND: U-NAG/creatinine ratio is a marker of renal
      tubular impairment and an increase in this ratio have been reported to affect the
      kidneys in various diseases. METHODS: The U-NAG/creatinine ratio was measured in
      the spot urine of 22 children (10 boys and 12 girls, mean age 2.83 +/- 2.42
      years) with VUR. In 8 patients The VUR was unilateral grade I-IV (8 patients),
      and it was was bilateral, grade I-V in 14 patients. In patients with bilateral
      reflux and different VUR grade on each side, the highest grade of VUR was taken
      into consideration. RESULTS: The U-NAG/Cr levels were significantly higher in VUR
      patients compared to the reference (p = 0.0001). There was no difference in U
      NAG/Cr between children with unilateral (n = 8) and bilateral (n = 14) VUR (p =
      0.66). There was no difference in U-NAG/Cr between patients with VUR grades I-III
      and IV-V (p = 0.67). The U-NAG/Cr activity was higher in patients with reflux
      nephropathy (RN; n = 9) when compared to reference data (p = 0.0001), however
      there was no difference in comparison to children without RN (p = 0.84).
      CONCLUSIONS: U-NAG/Cr increased in children with VUR grade I-V and there is a
      very weak relationship with the grade of VUR. U-NAG/Cr is a useful marker of
      renal tubular impairment, however there is poor relationship with the degree of
      kidney damage in patients with VUR (Tab. 1, Ref. 25). Full Text (Free, PDF)
      www.bmj.sk.

PMID- 19408835
TI  - Small bowel graft revascularization in experiment.
AB  - OBJECTIVES: The technical aspects of a procedure are most important for the
      outcome of the experiment. This study was designed to compare two techniques
      suitable for graft revascularization. METHODS: The first technique, where the
      animal is both donor and the recipient, consists of connecting the grafts'
      vascular anastomoses to the mesenteric vessel bed. In the second technique, one
      animal is the graft donor and the other is the recipient, with revascularization
      to the central vessel bed (subrenal inferior vena cava and aorta). Techniques of
      restoring digestive tract continuity and creation of diagnostic "chimney
      ileostomy" were identical in both groups. All experimental animals were monitored
      clinically regularly basis as per protocol (weight, temperature, stoma
      appearance, output and nature of stools). Blood and biopsy samples were obtained
      on days 0, 3, 5, 7, 10, 20, and 30. RESULTS: Overall, 43 transplant procedures
      were performed. The first group included 18 transplants and 66.7% animals had
      vascular complications. While in the second group (25 transplant procedures),
      vascular complication rate was only 12% (3 out of 25) perhaps due to technique
      modifications. CONCLUSION: Our experiment showed that both types of vascular
      anastomosis could be used in small bowel transplantation. Connecting the graft
      vessels to the aorta and inferior vena cava is technically simpler and safer
      because of fewer subsequent complications (Tab. 1, Fig. 4, Ref. 6). Full Text
      (Free, PDF) www.bmj.sk.

PMID- 19408837
TI  - Gene polymorphisms of renin angiotensin system and serotonin transporter gene in
      patients with vasovagal syncope.
AB  - Objective of this study was to compare the distribution frequencies of gene
      polymorphisms of renin-angiotensin and serotonin system in patients with positive
      and negative head- up tilt test (HUT). METHODS: DNA from 191 patients (mean age
      44+ 18 years, 61 men) was collected. HUT was positive in 117 and negative in 74
      patients. Following gene polymorphisms were determined by the PCR method: ACE
      insertion/deletion (I/D ACE), angiotensinogen (AGT) (M 235), angiotensin II
      receptor (ATR1) (A 1166C) and serotonin transporter (SERT) polymorphism
      (5HTTLPR). RESULTS: No significant differences in the distribution of gene
      polymorphisms between syncopal patients with positive and negative HUT were
      dectected. Distribution of polymorphisms included: I/D ACE: II 19 vs 20%, ID 55
      vs 52%, DD 26 vs 28%. Angiotensinogen gene polymorphism MM 27% vs 30%, MT 48% vs
      46%, TT 25% vs 24%. ATR1 polymorphism AA 44 vs 32%, AC50 vs 60%, CC 6 vs 8%,
      5HTTLPR serotonin transporter gene polymorphism LL 42 vs 43%, SL 41 vs 39%, SS 17
      vs 18%. CONCLUSIONS: An association between polymorphisms of ACE, AGT, ATR1 and
      SERT gene, and predisposition to VVS was not proven by the present study (Tab. 2,
      Ref. 22). Full Text (Free, PDF) www.bmj.sk.

PMID- 19408838
TI  - High virologic sustained response for former young intravenous drug users with
      chronic hepatitis C treated by pegylated interferon-alpha plus ribavirin.
AB  - AIMS: The aim of this clinical study was to assess virological response at end-of
      -treatment (ETR), sustained virological (SVR) and biochemical response in former
      drug users with chronic hepatitis C treated with PEG-IFN-alpha and R. PATIENTS:
      Ninety two former drug users (21 F, 71 M) average age 27 years (18 to 41 years)
      and previously not treated with IFN-alpha and R (naive patients, pts) were
      evaluated for their virological and biochemical response. Standard treatment
      regimen of either 24 or 48 weeks was applied in patients with genotype 3 or
      genotype 1, respectively. SVR was considered if viral tests (HCV RNA) were
      negative 24 weeks after the end of treatment. RESULTS: Overall SVR was attained
      in 87 (95%) of 92 treated patients, and therapy failed in 5 pts with genotype 1.
      In genotype 1 patients ETR and SVR were 81% and 86%, respectively (p < 0.001). In
      genotype 3 patients ETR and SVR were 98% and 100%, respectively (p < 0.001). ALT
      levels decreased significantly after 12 weeks of therapy (ALT 1.61 vs 0.64
      micro/kat/l, p < 0.001) and were at normal levels during follow-up. CONCLUSIONS:
      Crucial predictive factors resulting in high SVR were the younger age in
      combination with low stage of liver fibrosis, relatively short duration of viral
      infection, high proportion of genotype 3 and excellent adherence of patients to
      treatment regimen than previously not treated with IFN-alpha and R (naive
      patients). High proportion of SVR in former drug users has been achieved in
      patients with genotype 3 (100%) and genotype 1 (86%). The most decisive
      prognostic factor which favors high therapeutic efficacy appears to be young age
      and early onset of anti-HCV treatment (Tab. 3, Fig. 1, Ref. 33). Full Text (Free,
      PDF) www.bmj.sk.

PMID- 19408839
TI  - Genetic screening of patients with hypertrophic cardiomyopathy--a new diagnostic
      strategy for risk stratification?
AB  - Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited disease of
      the heart muscle and its main characteristic is unexplained hypertrophy of the
      left and/or the right ventricle. HCM is the most common genetically determined
      cardiovascular disease and is prevalent in approximately in 1 of 500 of the
      population. The most serious complication of HCM is sudden cardiac death (SCD)
      which can be the first manifestation of the disease. However, there are other
      forms of benign prognosis which do not jeopardize patient's health or life. The
      clinical symptoms of HCM are partly dependent on mutations in affected sarcomere
      genes. Different mutations in the same gene can present as malign with a high
      risk of SCD, while other mutations can be benign. The clinical symptomatology can
      also be influenced by other factors such as the presence of polymorphisms in
      other genes. Nowadays the aim of intensive clinical research is to access the
      contribution of molecular genetic methods in HCM diagnostics as well as in risk
      stratification of SCD. It is expected that genetic analyses will have an
      important consequence in the screening the relatives of HCM patients and also in
      the prenatal diagnostics and genetic counseling (Tab. 2, Fig. 1, Ref. 45). Full
      Text (Free, PDF) www.bmj.sk.

PMID- 19408840
TI  - Metallothionein--a promising tool for cancer diagnostics.
AB  - The latest research outcomes indicate that metallothionein (MT) levels in
      peripheral blood and serum from cancer patients can provide many interesting
      information about type or clinical stage of the disease, or response to therapy.
      MT plays a key role in transport of essential heavy metals, detoxification of
      toxic metals and protection of cells against oxidation stress. Serum MT levels of
      cancer patients are three times higher than control patients (0.5 microM). The
      elevated MT levels in cancer cells are probably related to their increased
      proliferation and protection against apoptosis. Automated electrochemical
      detection of MT allows its serial analysis in a very small volume with excellent
      sensitivity, reliability and reproducibility and therefore it can be considered
      as a new tool for cancer diagnosis (Fig. 4, Ref. 55). Full Text (Free, PDF)
      www.bmj.sk.

PMID- 19408841
TI  - Use of probiotics for prevention of radiation-induced diarrhea.
AB  - Probiotics can be applied in therapy and mainly in prevention of many
      civilization disorders. Experimental studies in animal models and clinical trials
      of patients with inflammatory bowel disease (IBD) have consistently shown that
      the use of probiotic organisms may effectively down-modulate the severity of
      intestinal inflammation by altering the composition and metabolic and functional
      properties of indigenous flora of the gut. Previous studies showed a protective
      effect of probiotic administration after radiation therapy, and probiotic may
      play an important role in the pathogenesis of radiation enteropathy. These
      studies indicate that probiotics may decrease the risk of accumulated reactive
      oxygen species (ROS) in host organisms and could potentially be used as probiotic
      food supplements to reduce oxidative stress (Tab. 2, Ref. 47). Full Text (Free,
      PDF) www.bmj.sk.

PMID- 19408842
TI  - Comorbidity psychiatric disorders in epilepsy: a review of literature.
AB  - While reviewing the available literature, we noticed comorbidity of epilepsy and
      psychiatric disorders. Psychiatric disorders were observed more frequently in
      patients with high seizure frequency. There is significant prevalence of epilepsy
      comorbidity with depression, anxiety disorders, and to a lesser extent with
      bipolar disorders and other forms of psychosis. Suicidal risk factors, ideation
      and attempts in these patients as correlates of depression or as
      psychopathological features were associated to epileptic disease. This is
      confirmed by additional burden of epilepsy patients with psychic disorders (Ref.
      70). Full Text (Free, PDF) www.bmj.sk.

PMID- 19408843
TI  - Controversy of the third molars.
AB  - Third molars are teeth that have little functional value and a relatively high
      rate of associated pain and disease. Their value as a part of the dentition of
      modern people is dubious. Our aim is to review the evolution, morbidity and
      complications of the third molars (Ref. 19). Full Text (Free, PDF) www.bmj.sk.

PMID- 19408844
TI  - Paradoxes in medicine: an access to new knowledge?
AB  - The analysis of health and nutrition data from various countries shows many
      surprising and seemingly incomprehensible facts and paradoxical relationships.
      Health status of a country is the result of long-term factors and therefore it
      cannot be changed from day to day. For example in Central European countries
      there was a sudden increase in life expectancy after the fall of Soviet hegemony.
      French paradox is the oldest example of apparent contrast between "unhealthy"
      nutrition and low cardiovascular mortality. Although, the consumption of animal
      fat and milk and milk products in Switzerland is very high, but premature
      cardiovascular mortality of Swiss men and women is the lowest in Europe. In USA
      there is concominant increase of obesity and decrease in cardiovascular
      mortality. In Cuba, in spite of great economic problems its relatively high male
      and female life expectancy is very similar to the rich USA. The life expectancy
      in Albania is significantly higher than in many countries in Central Europe and
      in the Balkan region, in spite of the fact that Albania remains the poorest
      European country. Analysis of these unexpected and paradoxical relations indicate
      the importance of the quality of medical care, control of cardiovascular risk
      factors (USA) and the influence of modest but biologically balanced diet on low
      prevalence of cardiovascular disease in Cuba and Albania. The experience from
      former communist Central European countries suggests important influence of
      chronic stress and psychosocial factors on heart diseases and life expectancy.
      These paradoxes open the door to new information (Fig. 5, Ref. 11). Full Text
      (Free, PDF) www.bmj.sk.

PMID- 19408845
TI  - Recurrent malignant epitheloid schwannoma of the lower lip.
AB  - The authors describe a case of recurrent malignant epitheloid schwannoma of the
      lower lip. Histologically, the tumor was composed of fibroblast-like spindle
      cells in compact fascicles and areas of epitheloid growth, combined with
      demonstration of S-100, GFAP and NF positivity, which is characteristic for this
      type of tumor. The therapy consisted of a combination of surgery and radiotherapy
      and the patient was followed-up since the disease was diagnosed. A local re
      operation had to follow the first surgical intervention consisting of a radical
      excision of tumor in the lower lip together with suprahyoid neck dissection six
      months later. After the first operation, the patient received a radiation therapy
      with a total dosage of 12 Gy in seven fractions to the tumor area of the lower
      lip. After the second operation, an external radiotherapy with total dosage of 50
      Gy was applied. Despite the complex intensive therapy, the patient died of
      metastases into lungs, liver and spine 37 months after the initiation of the
      therapy (Fig. 2, Ref. 17). Full Text (Free, PDF) www.bmj.sk.

PMID- 19408846
TI  - Imperforate hymen with hematocolpometra combined with elevated Ca125.
AB  - In the present case, ultrasound examination ruled out the presence of
      hematosalpinx or other gynecological tumors. This was of great importance to the
      surgical intervention, especially for avoiding laparotomy. Dilatation of the
      vagina and uterus, due to imperforate hymen with retrograde menstruation should
      be considered in the differential diagnosis of abdominal pain in premenarchal
      girls (Fig. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

PMID- 19408847
TI  - [The solution of persistent stress urinary incontinence in women when surgery
      with the TVT-SECUR* is unsuccessful].
AB  - OBJECTIVE: The objective of this study is to evaluate the efficacy of the
      procedure of shortening the tape in the treatment of persistent stress urinary
      incontinence when the tension-free vaginal tape (TVT) SECUR procedure proves
      unsuccessful. DESIGN: Retrospective study. SETTINGS: Department of Gynecology and
      Obstetrics, First Faculty of Medicine, Charles University and General Teaching
      Hospital, Prague. MATERIALS AND METHODS: Eight patients with persistent stress
      urinary incontinence (SUI) after the TVT-S procedure were included in our study.
      In order to resolve their condition, the tape was shortened. We used the overlap
      and the cut-off technique. Pre- and postoperative urodynamic and ultrasound (US)
      examinations were carried out, and the efficacy of this procedure was evaluated
      by cough test, pad-weighting test (PWT) and by the questionnaires Pelvic Organ
      Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ12) and the
      International Consultation on Incontinence Questionnaire--Short form (ICIQ-UI
      SF). All data were processed and statistical analyses performed in statistical
      environment R, version 2.5.1. RESULTS: In six patients the cough test and PWT
      were negative after reoperation, indicating no stress urinary incontinence, while
      in two patients mild leakage of urine persisted. The reoperation significantly
      increased the value of Maximum Urethral Closure Pressure (MUCP) while coughing.
      From the US examination we can conclude that the tape is tightened closer to the
      urethra and pubic bone. CONCLUSIONS: We describe a method--shortening the tape-
      for the treatment of persistent stress urinary incontinence when the TVT-S
      procedure fails. Based on our results we have established that this procedure is
      simple and as effective as inserting a new tape, but cheaper.

PMID- 19408848
TI  - [Bioimpedance analysis--a new method in prediction and early detection of ovarian
      hyperstimulation syndrome?].
AB  - OBJECTIVE: The aim of the study was to establish a new method of the multiple
      frequency bioimpedance analysis (MFBIA) for patients with controlled ovarian
      hyperstimulation (COH) and to determine the significance of this method in
      prediction and early diagnosis of severe forms of ovarian hyperstimulation
      syndrome (OHSS). DESIGN: Prospective case control study. SETTING: Department of
      Obstetrics and Gynecology, 2nd Medical Faculty, Charles University and University
      Hospital Motol, Prague. METHODS: 53 patients were recruited into the case control
      study. The surface body impedances for the frequencies of the current 1, 5, 50
      and 100 kHz were measured. Study group included 13 patients with developed OHSS
      grade III.-V. according Golans classification. The control group included 40
      women undergoing COH without developed OHSS. Measurements of impedances were
      performed by MFBIA device. RESULTS: The decrease of the values of impedance
      between the day of oocyte retrieval and the day of embryotransfer significantly
      increases relative risk of OHSS grade III.-V. development. The best correlation
      was found for the frequency of 5 kHz (9.08 p<0.0001). The study suggests, the
      predictive value of MFBIA in OHSS development might be higher than the number of
      retrieved oocytes (>20 oocytes-RR 5,71). CONCLUSION: Patients in risk of OHSS
      development are those with decreasing impedances. The highest predictive value of
      OHSS development is for the impedances at frequency of 5 kHz. Greater multicenter
      studies should be done to confirm our preliminary results.

PMID- 19408850
TI  - [The diagnostic value of hysterosalpingography in the diagnosis of tubal
      disease].
AB  - OBJECTIVE: To present an overview of trials and discussion focused on the
      diagnostic value of hysterosalpingography in the diagnosis of tubal disease.
      SUBJECT: Review article. SETTING: Sanatorium Pronatal, Prague. CONCLUSIONS:
      Hysterosalpingography may be a screening test for tubal patency. Data
      demonstrates high specificity of hysterosalpingography for diagnosis of proximal
      tubal occlusion or hydrosalpinx and low sensitivity in cases with peritubal
      adhesions. Routine use of diagnostic laparoscopy should be delayed for
      asymptomatic women. It is expected hysteroscopy and transvaginal hydrolaparoscopy
      for asymptomatic women may decrease indications for diagnostic laparoscopy with
      complete visualization of the pelvic cavity.

PMID- 19408849
TI  - [Thyroid gland in the gravidity].
AB  - OBJECTIVES: Disorders of the thyroid gland are the most common endocrinopathies
      in the gravidity. The spectrum of thyroid diseases in the pregnancy is not
      different from the diseases that affect the thyroid outside this period of life.
      However, clinical manifestations of thyreopaties can be modified by gravidity.
      Some thyreopaties are associated with gravidity or post partum period, or become
      manifest in this periods for the first time. The aim of this study was to assess
      thyroidal status of healthy pregnant women without history or clinical signs of
      thyreopathy. TYPE OF THE STUDY: One-time cross-sectional study. SETTING: 3rd
      internal clinic FNLP, Kosice. METHODS: We examined 76 pregnant women (mean age
      34.46 +/- 5.34 years). The protocol included medical history, physical
      examination and assessment of TSH, fT4 and anti-TPO concentrations. RESULTS: The
      mean concentration of TSH was 2.78 +/- 1.25 mlU/ml. We found TSH concentration
      over 5.0 mlU/ml in 5 participants (6.58%), TSH levels in the borderline range
      between 4.0-5.0 mlU/ml had another 2 pregnants (2.63%). fT4 concentration was
      15.02 +/- 3.61 pmol/l. The mean anti-TPO concentration was 43.28 +/- 15.75 IU/ml.
      17 pregnant women (22%) had anti-TPO concentration over 25 IU/ml, which is the
      level that indicates autoimmune thyroiditis. CONCLUSIONS: Thyreopathies are the
      most common endocrinopathies in the population and there is the evidence that
      almost one third of European population is affected from diseases of thyroid
      gland, predominantly women in fertile age. In the clinical praxis it is essential
      to think of thyroid disorders and in the case of need screening of the thyroid
      function.

PMID- 19408851
TI  - [News and perspectives in uterine fibroids radiotherapy].
AB  - Uterine artery embolization (UAE) represents radiological treatment of uterine
      fibroids. It is highly effective and safe mainly in premenopausal patients with
      symptomatic fibroids and represents an alternative to hysterectomy in a group of
      women not suitable for minimally invasive surgical treatment (LAVH) and women
      desiring uterus sparing therapy. The future of UAE lies in optimal selection of
      patients based on volume-shrinkage prediction and fertility outcome. The second
      group is represented by methods based on direct fibroid tissue destruction using
      specific energy under MRI or UZ guidance. The common aim of these two groups is
      the volume shrinkage as well as the symptomatic relief. The second group is
      represented by radiofrequency ablation, focused ultrasound surgery, interstitial
      laser ablation and cryotherapy. Based on their non-surgical, percutaneous
      approach these can be classified as minimally-invasive methods. The second group
      of methods is suitable only for patients with the absence of any desire for child
      bearing due to the absence of their long-term outcome data.

PMID- 19408852
TI  - [The lifestyle of Pilsner University female students and its effect on vaginal
      mycosis].
AB  - BACKGROUND: Up to now, it does not exit whole look at the life quality of the
      Pilsner female University students, especially in connection with gynecological
      history. It is reality that in last years the number of gynecological problems
      among young women increases such as the number of diseases with immunological
      background. METHOD: We prepared questionnaire with 36 questions directed to life
      style, gynecological history, partner's life, food and hygienic habits, and
      nicotinism. RESULTS: 28 female students from the total group of 141 suffered from
      vaginal mycosis--22 (78.6%) use pills, 6 (21.4%) no hormonal contraception. 17
      (60.7%) prefer flyaway cloth and 9 (32.1%) tight cloth. 141 students mentioned
      various number (0-25) of their sexual partners: 1-3 (79 students) in 15 cases
      (19%) mycoses, more than 4 partners (49 students) in 13 (26.5%) mycoses appeared.
      The first menstruation appeared in o 13 years (10-17 years). High incidence of
      vaginal mycosis was proven in students using only tampons than hygienic towels.
      CONCLUSION: Vaginal mycosis is affected by many endogenous and exogenous factors.
      The main factors in pilsner university female students are hormonal
      contraception, promiscuity and hygienic habits.

PMID- 19408853
TI  - [Birth defects in the Czech Republic in 1994--2007].
AB  - AIM OF STUDY: An analysis of occurrence of birth defects in the Czech Republic in
      1994-2007. An assessment of total numbers and relative incidences of birth
      defects in births according to Tenth Revision of International Classification of
      Diseases (ICD-10). TYPE OF STUDY: Retrospective epidemiological analysis of birth
      defects incidences from the Czech National Birth Defects Register database.
      MATERIAL AND METHODS: Data from the National Birth Defects Register (Institute
      for Health Information and Statistics) in the Czech Republic in the 1994-2007
      period were used. In this study, particular diagnoses--as they were registered in
      the National Register--were analyzed. The diagnoses in study were divided into
      following eleven birth defects groups according to ICD-10 classification: (Q00
      Q07) nervous system, (Q10-Q18) eye, ear, face and neck, (Q20-Q28) circulatory
      system, (Q30-Q34) respiratory system, (Q35-Q37) cleft lip and cleft palate, (Q38
      Q45) digestive system, (Q50-Q56) genital organs, (Q60-Q64) urinary system, (Q65
      Q79) musculoskeletal system, (Q80-Q89) other defects and (Q90-Q99) chromosomal
      abnormalities, not elsewhere classified. Prenataly diagnosed cases are not
      included. RESULTS: During 1994-2007 period, totally 1,353,040 children were born
      on the area of the Czech Republic, out of which 44,343 with a birth defect. The
      diagoses in study were divided into eleven groups according to ICD-10
      classification. Further, particular diagnoses according to ICD-10 and their
      verbal descriptions are presented in tables. Each group is accompanied by data on
      its total number and a relative incidence (per 10,000 live births) with a 95%
      C.I.. A relative frequency of the birth defects groups in study (in % from the
      total number of birth defects) is as follows: (Q00-Q07) nervous system 2.10, (Q10
      Q18) eye, ear, face and neck 4.76, (Q20-Q28) circulatory system 39.63, (Q30-Q34)
      respiratory system 1.03, (Q35-Q37) cleft lip and cleft palate 3.67, (Q38-Q45)
      digestive system 4.05, (Q50-Q56) genital organs 10.93, (Q60-Q64) urinary system
      7.08, (Q65-Q79) musculoskeletal system 18.90, (Q80-Q89) other defects 5.55 and
      (Q90-Q99) chromosomal abnormalities 2.28. CONCLUSIONS: The study gives updated
      results of incidences analysis of postnatally diagnosed birth defects (available
      on the date of August 31, 2008) in the Czech Republic in the 1994-2007 period.
      Data on birth defects were collected in the National Birth Defects Register
      (Institute for Health Information and Statistics). Birth defects registration is
      a compulsory process and is a part of the National Health Information System. The
      diagnoses in study were divided into eleven groups according to ICD-10
      classification. Total numbers, relative incidences (per 10 000 live births, with
      a 95% C.I.) and relative frequencies of the birth defects groups are presented.

PMID- 19408855
TI  - [News in pathophysiology and management of preterm labour].
AB  - OBJECTIVE: To summarize available data concerning pathophysiology and management
      of preterm labour and their use in clinical practice. SETTING: Department of
      Obstetrics and Gynecology od the First Faculty of Medicine, Charles University,
      and General Teaching Hospital, Prague. DESIGN: Review article. METHODS:
      Compilation od published data from scientific literature. CONCLUSION: Birth canal
      infections seem to play a key role in the ethiopathogenesis of premature
      delivery; the related biochemical changes significantly affect perinatal
      morbidity and mortality. Other potential causes, particularly hormone metabolism
      disorders or uteroplacental ischaemia have been intensively studied. The
      particular pathogenetic process of premature delivery is inflammation. This
      process is related to both mother and fetus. Fetal inflammatory response (FIRS)-
      can occur without maternal response--is connected with significant increase in
      perinatal morbidity. FIRS is characterised by defined laboratory, histological
      and clinical criteria. Effective primary prevention of premature delivery does
      not exist at present. The sensitivity and specificity of the laboratory markers
      having been used so far is low. Thus, the research is focused on finding new
      inflammation markers to allow early identification of pregnant women at a high
      risk of premature delivery and fetal inflammation. The screening of women at a
      high risk by means of new laboratory and ultrasound tests belongs to the most
      important steps in secondary and tertiary prevention of premature delivery.
      Intensive research of potential trigger mechanisms has been carried out,
      including a variety of gene types, which are potentially related to the process
      of premature delivery. We try to exercise new informations about pathophysiology
      of preterm labour in prenatal care, firstly about thrombophillias and gestagens.
      We also use a principles of "evidence based medicine" and revalue importance of
      steroids, tocolytics and antibiotics.

PMID- 19408854
TI  - [Prenatal diagnostics of chromosomal aberrations Czech Republic: 1994-2007].
AB  - AIM OF STUDY: An analysis of prenatal diagnostics efficiency of selected types of
      chromosomal aberrations in the Czech Republic in 2007. Update of 1994-2007 data
      according to particular selected diagnoses. TYPE OF STUDY: Retrospective
      epidemiological analysis of pre- and postnatal chromosomal aberrations
      diagnostics and its efficiency. MATERIAL AND METHODS: Data on pre- and
      postnatally diagnosed birth defects in the Czech Republic during 1994-2007 were
      used. Data on prenatally diagnosed birth defects (and for terminated pregnancies)
      were collected from particular departments of prenatal diagnostics, medical
      genetics and ultrasound diagnostics in the Czech Republic, data on birth defects
      in births from the National Birth Defects Register (Institute for Health
      Information and Statistics). Total numbers over the period under the study, mean
      incidences of selected types of chromosomal aberrations and mean prenatal
      diagnostics efficiencies were analyzed. Following chromosomal aberrations were
      studied: Down, Edwards, Patau, Turner and Klinefelter syndromes and syndromes
      47,XXX and 47,XYY. RESULTS: A relative proportion of Down, Edwards and Patau
      syndromes as well as other autosomal and gonosomal aberration is presented in
      figures. Recently, trisomies 13, 18 and 21 present around 70% of all chromosomal
      aberrations in selectively aborted fetuses, in other pregnancies, "other
      chromosomal aberrations" category (mostly balanced reciprocal translocations and
      inversions) present more than 2/3 of all diagnoses. During the period under the
      study, following total numbers, mean relative incidences (per 10,000 live births,
      in brackets) and mean prenatal diagnostics efficiency (in %) were found in
      following chromosomal syndromes: Down syndrome 2,244 (16.58) and 63.37%, Edwards
      syndrome 521 (3.85) and 79.93%, Patau syndrome 201 (1.49) and 68.87%, Turner
      syndrome 380 (2.81) and 79.89%, 47,XXX syndrome 61 (0.45) and 59.74%, Klinefelter
      syndrome 163 (1.20) and 73.65% and 47,XYY syndrome 22 (0.16) and 54.76%.
      CONCLUSIONS: The study gives updated results of incidences analysis of both pre-
      and postnatally diagnosed chromosomal birth defects in the Czech Republic during
      the 1994-2007 period. Incidences found in our study correspond (in case of
      trisomies 13, 18 and 21) with those published widely in literature as well as
      with those found in large-scale international studies (ICBDSR, EUROCAT). In case
      of gonosomal aberrations, incidences found in this study are lower that those
      published, most probably due to a later registration (over 15 years of age of the
      child) of these diagnoses.

PMID- 19408857
TI  - [Appendix protrusion from perforation of uterus--the rare complication during
      abortion].
AB  - AIM: Point to an extremly rare complication of a curettage during abortion and
      follow up surgical treatment of this complicated state. CASE: In the case of 32
      years old woman, multipara, was perforated cervix uteri during the abortion
      curettage and fat tissue of mesentery was aspirated into canulla. Apendix
      vermiformis was aspirated into cannula with its protrusion through the neck of
      the womb during repeated revision. Surgeon made appendectomy lege artis after
      abdomen revision and looking after haemoperitoneum. Because of serious
      devastation of right fallopian tube, salpingektomy was performed. Perforation of
      cervix in the lenght of three cm was sutured. Extensive incomplete rupture
      continuing from perforation gap was sutured from ligamentum sacrouterinum I.dx to
      fundus uteri. Intact foetus of 5,5 week of gestation was leaved in toto because
      of the high risk of the womb wall disruption during repeatedly attempted
      abortion. CONCLUSION: In case of the suspection of the uterus injury a revision
      and interdisciplinary approach to the solution of complications is necessary.

PMID- 19408856
TI  - [Spontaneous symphysis pubis rupture followed by intraabdominal bleeding during
      the vaginal delivery].
AB  - Symphysis pubis rupture is rare but life-threatening complication of vaginal
      delivery. Prompt diagnosis and therapy of this complication is crucial. We
      present a case report of a patient with a symphysis pubis rupture followed by
      severe intraabdominal bleeding. The therapy of symphysis pubis rupture is usually
      conservative according to the available sources. In the case of our patient
      osteosynthesis was performed with an excellent result.

PMID- 19408858
TI  - [Influence of haemorheopheresis in the dry form of the age related macular
      degeneration].
AB  - INTRODUCTION: The age related macular degeneration (ARMD) is the most common
      cause of practical blindness in the population older than 60 years of age.
      Usually it starts as a dry form with soft drusen.The progression of the dry form
      is difficult to control-promising seems to be the influence of rheologic factors
      in the choroid and the retina and thus improvement of their blood flow. AIM: By
      means of haemorheopheresis to improve blood rheology and thus micocirculation in
      the choroid and retina. The authors describe the development of the dry form of
      the ARMD in the sensitive stage with soft drusen and the eventual presence of
      retinal pigment epithelium detachment (RPED) after haemorheopheresis. The treated
      patients were compared with a control group (natural course of the ARMD) with the
      same number of patients. METHODS: In a prospective, randomized study, comprising
      of 16 patients with the dry form of ARMD were treated with haemorheopheresis
      (cascade filtration) and 16 patients in the control group. Haemorheopheresis
      treatment comprised of 8 cycles in 10 weeks. Plasma obtained by separator was
      filtered by the Evaflux 4A (Japan) separator, where, the defined spectrum of high
      molecular proteins was captured. This lead to a decrease in blood and plasma
      viscosity and thus to improvement of rheologic conditions of the retina. RESULTS:
      Results show a positive influence on the absorption of soft drusen, reduction of
      the retinal pigment epithelium detachment, and the possibility to improve the
      visual acuity of the treated patients. CONCLUSION: Comparing to the worsening of
      clinical signs and visual functions in natural course of the ARMD development,
      the rheopheresis as well tolerated method may cause the retardation or stop of
      the unfavorable course of the disease.

PMID- 19408859
TI  - [European cataract outcome study--evaluation of 3 years in European study].
AB  - AIM: The aim of this paper is to publish results from the Department of
      Ophthalmology, Regional hospital Pardubice, Czech Republic, E.U., obtained at our
      workplace during the period 2003 to 2005 for the all-European study with the
      title: European Cataract Outcome Study. METHODS: European Cataract Outcome Study
      is international all-European study monitoring availability of the cataract
      surgery in different parts of the Europe and it follows up the quality of the
      cataract surgeries in separately entered departments. Its goal is to incite the
      development of cataract surgery and extend new technologies of cataract surgery
      and use the findings for determining indication and timing of the surgery for the
      evaluation of the profit the patients have from cataract surgery. This study
      evaluates yearly the results of primary cataract surgery provided during one
      month of the year--October. The study has been proceeding since 1995; we have
      been participated in it since 2003 and cooperated up to the present day. In the
      first part of study, there are followed up the basic demographic data with pre
      operative investigation and course of the cataract surgery, in the second part
      results of post-operative investigations during 6 months after the surgery.
      RESULTS: The patients in our department are in entire majority operated in local
      subconjunctival anesthesia by means of phacoemulsification with implanted
      foldable lenses, whose number rises along assessed years from 51% to almost 100%
      of cases. European tendency is out-patient cataract surgery; in our department,
      there're patients hospitalized in 60-62.9% of cases. During three years we have
      noted attendance of associated disorders in 28-45% of cases. The post-operative
      best-corrected visual acuity 0.5 and better up to 6 months after the surgery is
      in 86-90% of cases.The intended postoperative refraction was from -0.40 to -0.48
      diopters (dpt), the final post-operative error from the planned refraction was
      1.2 dpt. The average of induced astigmatism is 0.61 cylindrical diopters. The
      ascertained difference between operated and non-operated eye was 0.8-0.9 dpt,
      after the operation of the fellow eye it was 1.12-1.2dpt. CONCLUSION: Our results
      are approximately comparable with the condition of the ophthalmologic care in
      Europe and they correspond to the European average.

PMID- 19408860
TI  - [Statistical analysis of the nerve fiber layer in color digital images of the
      retina].
AB  - The topic of the article is to inform about the analysis of the nerve fiber layer
      in color digital images of the retina. The study group consists of 11 eyes (9
      patients) with marked focal losses in the nerve fiber layer of the retina. The
      control group consists of 14 eyes (7 patients). The basic statistical parameters,
      which may distinguish the loss in the nerve fiber layer from the healthy nerve
      fiber layer, are suggested and evaluated. The study is focused particularly to
      detect the focal losses.

PMID- 19408861
TI  - [Septo-optic dysplasia--omitted interdisciplinary clinic entity: report on three
      patients].
AB  - On example of three patients with septo-optic dysplasia the authors present a
      rare clinical entity involving combined disturbances of endocrine and neurologic
      systems and variable expressed clinical triad: 1) pituitary aplasia/dysplasia
      with pituitary hormones deficiency, 2) developmental disturbance of the middle
      brain structures (corpus callosum and septum pellucidum), and 3) dysplastic
      changes of the optic nerve. The knowledge about components belonging to the
      competence of other specialists and awareness of consequences of untreated
      hypopituitarism, are imperatives for interdisciplinary cooperation of
      ophthalmologist, neurologist, radiologist, and endocrinologist. Moreover, they
      predict early initiation of the adequate and often vital therapy. Molecular
      genetic studies in patients with septo-optic dysplasia represent a way to better
      knowledge about early stages of the pituitary gland and brain development.

PMID- 19408862
TI  - [Central serous choroidopathy as rare complication of the corticosteroid
      treatment].
AB  - The secondary glaucoma and complicated cataract are known and frequent
      complications of the corticosteroid treatment. The central serous choroidopathy
      (CSCH) is rare complication of corticotherapy in which occurs the focal serous
      ablation of the neurosensoric retina in the macular region caused by means of the
      leakage of the fluid trough the damaged retinal pigment epithelium. The authors
      present 5 cases of the CSCH during the corticosteroid treatment period, or the
      worsening of the already existing disease after the corticosteroid treatment.
      Despite the generally recognized fact the corticosteroids may precipitate the
      CSCH and they are contraindicated in its treatment, we repeatedly meet patients
      with this diagnosis, who are treated by means of systemic or parabulbar
      corticosteroids.

PMID- 19408863
TI  - [Contrast sensitivity in refractive surgery].

PMID- 19408864
TI  - [A tree-like body].

PMID- 19408865
TI  - [Liver transplantation: how to manage organ shortage?].
AB  - Organ shortage remains a major problem in liver transplantation for which the
      number of patients on the waiting list is superior to the number of liver grafts
      harvested each year. In 2007, 1061 liver transplantations have covered 78.7% of
      the needs for 1348 new candidates. Improvement of the results (5 year-survival
      74.9% and 63% at 10 years) do not influence the number of major indications
      (hepatocellular carcinoma, hepatitis C virus, alcohol), despite a slight decrease
      in the rate of activity of 1 to 2% per year. Introduction of the national score
      for each patient to be registered on the waiting list, the use of split grafts or
      grafts from marginal criteria donors may enlarge the donor pool. Liver grafts
      from cardiac deceased donors or from living donors are less frequent and are
      controversial from a technical and psychological point of view. The most
      efficient solution in order to overcome organ shortage is the increase in the
      pool of brain dead donors by accompanying people acceptance of organ donation and
      the use of parts of human body after death. Such education of the population
      could be made by the valorisation of organ donation, through public campaigns
      suggesting reflexion rather than coercition.

PMID- 19408866
TI  - [Otospongiosis].

PMID- 19408867
TI  - [Flavored cigarettes, a new weapon from the tobacco industry].

PMID- 19408868
TI  - [Lymphomas and infections].
AB  - The incidence of non-Hodgkin lymphoma (NHL) has more than doubled in the last 20
      years. The various mechanisms underlying malignant transformation of lymphoid
      cells all lead to an increased cellular proliferation and/or inhibition of
      apoptosis. Many infectious agents favor the development of NHL. Direct infection
      by lymphotropic viruses establishing a latent infection, such as the Epstein-Barr
      virus, interferes with cellular homeostasis and contribute to lymphoid
      transformation. Other infectious agents inducing chronic infections but unable to
      directly infect lymphocytes may also induce NHL. In this case, the sustained
      lymphoid proliferation induced by the persistent pathogen, increases the
      likelihood of malignant transformation, as exemplified by Helicobacter pylori
      associated gastric MALT NHL. Identification of an associated infection in the
      setting of a NHL is important as eradication of the pathogen by antimicrobial
      therapy may lead to tumor regression.

PMID- 19408870
TI  - [Diogenes syndrome].
AB  - Diogenes syndrome is mostly a complaint from the caregiver or neighbours. Its
      psychopathological signification isn't so easy to disclose.

PMID- 19408869
TI  - [Staphylococcus aureus musculocutaneous abscess, thrombophlebitis and
      spondylodiscitis].

PMID- 19408871
TI  - [Geriatric oncology. Integrating the elderly in the program].

PMID- 19408872
TI  - [Demography and epidemiology facts in geriatric oncology].
AB  - For decades, the ageing of the French population is constant. It is about an
      important phenomenon with a clean active dynamics. In 2050, the persons of more
      than 60 years will represent 33% of the population, and the 85 years and more 7%.
      Jointly the incidence of the cancer increases considerably after 65 years. This
      conjunction makes that more than a cancer on two occurs in elderly patients.
      Mortality by cancer in this age bracket does not know the favorable evolution
      observed in young people. This is related to more advanced stages of the disease
      at the time of diagnosis, with the rarer use to active therapeutics. However the
      elderly would like as younger people to receive an effective treatment of their
      cancer. The general practitioner has a fundamental role to play in the early
      diagnosis and in the participation to the management of cancer patient.

PMID- 19408873
TI  - [Geriatric assessment: principles and feasibility in oncology].
AB  - Geriatric assessment is a method aimed to describe elderly individual's health
      status. Effectiveness has been demonstrated in different domains. The ultimate
      outcome of Comprehensive Geriatric Assessment is the development of a coordinated
      care plan in which geriatric interventions focus on the particular problems of
      each patient. In the oncology setting, the method may help to estimate 1) the
      real place of cancer among the whole set of patient's health problems, 2)
      patient's tolerance to cancer treatments, and 3) treatment benefit/risk balance.
      Primary care providers play a pivotal role along the process, in strong
      collaboration with geriatricians and oncologists. This new pattern of
      interdisciplinary collaboration is currently being evaluated in Pilot Units of
      Coordination in Geriatric Oncology.

PMID- 19408874
TI  - [French National Cancer Institute (INCa) policy: geriatric oncology mission].

PMID- 19408875
TI  - [Decision making in geriatric oncology].
AB  - The decision making process, based on screening, diagnostic, staging, therapeutic
      and multidisciplinary decision procedures, is very well defined in oncology.
      Recently the same approach has been applied to the management of senior adult
      cancer patients. Screening of geriatric problems and evaluation of health status
      are linked to the oncologic evaluation. A comprehensive knowledge of the
      different health problems is discussed through a multidisciplinary approach. This
      needs a specific organization and collaboration between oncologists and
      geriatricians. It requires also the elaboration of specific decision trees of
      cancer adapted to the case of senior adult patients.

PMID- 19408876
TI  - [Are drug trials specific to geriatric oncology needed?].

PMID- 19408877
TI  - [Specific toxicities of chemotherapy in senior adult patients].

PMID- 19408878
TI  - [Clinical management of the most important cancers in older patients].
AB  - The clinical management of cancer in senior adult patients is based on the
      results of clinical trials which were performed in adults, generally younger
      adult patients. It is therefore difficult to assess the feasibility of such
      treatments, mainly chemotherapy, in older patients. The evaluation of health
      status is an important step in the decision making of cancer treatment in senior
      adults. In non Hodgkin lymphomas, the standard treatment remains chemotherapy
      with Rituximab. Specific protocols and treatment adaptation have been proposed in
      very old seniors. Surgery is a very efficient treatment in breast cancer,
      colorectal cancer and sometimes in non small cell lung cancer. Radiotherapy is
      important in the curative management of prostate cancer and in the
      multidisciplinary treatment of breast, colorectal and lung cancers. Chemotherapy
      is generally feasible in senior adults. However, Cisplatin is often too much
      toxic. Chemotherapy has a palliative impact in the treatment of metastatic
      prostate and breast cancers. It would be discussed in some high-risk groups of
      patients with breast and colorectal cancers. New targeted drugs are active in
      breast, colorectal cancers and in non Hodgkin lymphomas. Indications of treatment
      tailored on health status evaluation are discussed in the manuscript.

PMID- 19408879
TI  - [Infiltrating bladder cancer: clinical case].

PMID- 19408880
TI  - [Medical specialities in MeSH terms].

PMID- 19408881
TI  - [Abdominal aortic aneurysms in elderly subjects].
AB  - Abdominal aortic aneurysms (AAA) preferentially affect elderly subjects,
      especially men. Its pathogenesis is complex and multifactorial and even if
      clinical and fundamental research has led to a better understanding of the
      disease, several aspects remain unknown. Natural history consists of progressive
      aneurismal expansion leading to rupture which is associated with a high mortality
      rate (48.5% in-hospital and 80% global mortality). Screening for AAA and regular
      follow-up have been recognized as efficient strategies in order to prevent
      rupture, and screening programs have now to include women because the prognostic
      of the disease is more severe in women. Medical management of patients with AAA
      includes both limitation of aneurismal expansion rate and treatment of associated
      cardiovascular risk factors. Intervention is proposed when the maximal diameter
      of AAA reaches 50-55mm in men, and 45-50mm in women and the choice between open
      or endovascular repair depends on comorbidities and AAA anatomy. New therapies
      including specific therapy of the aneurismal wall such as cell or gene therapy
      could be proposed in the future.

PMID- 19408883
TI  - [Principles of evaluation of diagnostic tests].

PMID- 19408882
TI  - [Patient centered care: a truism?].

PMID- 19408884
TI  - [Diplopia].

PMID- 19408885
TI  - [Weight loss. Diagnostic guide].

PMID- 19408886
TI  - [Colon and rectal tumours].

PMID- 19408887
TI  - [Deep venous thrombosis and pulmonary embolism].

PMID- 19408888
TI  - [Tuberculosis].

PMID- 19408889
TI  - [Shock].

PMID- 19408890
TI  - [Syncope, loss of consciousness, and seizures in the adults].

PMID- 19408891
TI  - [Disease majesty and servitudes: Louis XIV's anal fistula].

PMID- 19408892
TI  - Biotransformation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in lung
      tissue from mouse, rat, hamster, and man.
AB  - Exposure to the tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK) is considered to be an important etiological risk
      factor for lung cancer in tobacco users. The metabolism of NNK via carbonyl
      reduction to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), alpha
      hydroxylation to form both DNA methylating and pyridyloxobutylating
      intermediates, and detoxification by pyridyl N-oxidation and glucuronide
      formation are well-characterized in laboratory animals but less so in man. The in
      vitro kinetics of 0.03-250 microM [5-(3)H]NNK metabolism were determined under
      identical experimental conditions using female A/J mouse, male Fischer 344 rat,
      female Syrian golden hamster, and human lung tissue explants in tissue culture.
      The concentration-dependent percentage contribution of the three major pathways
      of NNK metabolism (carbonyl reduction, alpha-hydroxylation, and N-oxidation)
      showed large interspecies variation. Quantitatively, in mouse, carbonyl reduction
      to NNAL increased steadily with an increasing substrate concentration (10-74%
      total NNK metabolism), while concurrent decreases occurred in end products of
      alpha-hydroxylation (60 to 18%) and N-oxidation (42 to 5%). In rat lung, there
      were no apparent concentration-dependent trends (NNAL, 42 +/- 4%; alpha
      hydroxylation, 35 +/- 2%; and N-oxidation, 24 +/- 3%). In hamster lung, a clear
      concentration-dependent increase in the contribution of NNAL to total NNK
      metabolism (from 47 to 87%) was paralleled by a steady decline in end products of
      alpha-hydroxylation (31 to 11%) and N-oxidation (22 to 2%). Human lung metabolism
      showed no concentration-dependent tendencies (NNAL, 89 +/- 1%; alpha
      hydroxylation, 8.8 +/- 1.1%; and N-oxidation, 2.1 +/- 0.3%). The major alpha
      hydroxylation product in human lung was 4-hydroxy-1-(3-pyridyl)-1-butanone (keto
      alcohol), thus supporting the potential pyridyloxobutylation of lung DNA.
      Metabolism to 4-(3-pyridyl)-4-oxobutanoic acid (keto acid), which could result in
      lung DNA methylation, was only sporadically seen in human lung but present to a
      far greater extent in rodent lung. No evidence for glucuronidation was found in
      any species. Generally, the rate of formation of all NNK metabolites showed two
      different enzyme kinetics, resulting in large differences between apparent K(m)
      and V(max) values in the low (up to 2.8 microM) and high substrate concentration
      ranges. The metabolism of NNK by alpha-hydroxylation is considerably lower in
      human lung as compared to that observed in rodent species, suggesting that
      extrapolation of in vitro rodent data to man may result in invalid conclusions
      about the capacity of the human lung to activate NNK under realistic conditions
      of NNK exposure expected to occur in man.

PMID- 19408893
TI  - Potential mechanism for pentachlorophenol-induced carcinogenicity: a novel
      mechanism for metal-independent production of hydroxyl radicals.
AB  - The hydroxyl radical ((*)OH) has been considered to be one of the most reactive
      oxygen species produced in biological systems. It has been shown that (*)OH can
      cause DNA, protein, and lipid oxidation. One of the most widely accepted
      mechanisms for (*)OH production is through the transition metal-catalyzed Fenton
      reaction. Pentachlorophenol (PCP) was one of the most widely used biocides,
      primarily for wood preservation. PCP is now ubiquitously present in our
      environment and even found in people who are not occupationally exposed to it.
      PCP has been listed as a priority pollutant by the U.S. Environmental Protection
      Agency (EPA) and classified as a group 2B environmental carcinogen by the
      International Association for Research on Cancer (IARC). The genotoxicity of PCP
      has been attributed to its two major quinoid metabolites: tetrachlorohydroquinone
      and tetrachloro-1,4-benzoquinone (TCBQ). Although the redox cycling of PCP
      quinoid metabolites to generate reactive oxygen species is believed to play an
      important role, the exact molecular mechanism underlying PCP genotoxicity is not
      clear. Using the salicylate hydroxylation assay and electron spin resonance (ESR)
      secondary spin-trapping methods, we found that (*)OH can be produced by TCBQ and
      H(2)O(2) independent of transition metal ions. Further studies showed that TCBQ,
      but not its corresponding semiquinone radical, the tetrachlorosemiquinone radical
      (TCSQ(*)), is essential for (*)OH production. The major reaction product between
      TCBQ and H(2)O(2) was identified to be trichloro-hydroxy-1,4-benzoquinone (TrCBQ
      OH), and H(2)O(2) was found to be the source and origin of the oxygen atom
      inserted into this reaction product. On the basis of these data, we propose that
      (*)OH production by TCBQ and H(2)O(2) is not through a semiquinone-dependent
      organic Fenton reaction but rather through the following novel mechanism: a
      nucleophilic attack of H(2)O(2) to TCBQ, leading to the formation of an unstable
      trichloro-hydroperoxyl-1,4-benzoquinone (TrCBQ-OOH) intermediate, which
      decomposes homolytically to produce (*)OH. These findings represent a novel
      mechanism of (*)OH formation not requiring the involvement of redox-active
      transition metal ions and may partly explain the potential carcinogenicity of the
      widely used biocides such as PCP and other polyhalogenated aromatic compounds.

PMID- 19408894
TI  - Influence of mechanical properties of nanoparticles on macrocrack formation.
AB  - We present an experimental investigation of drying suspensions of both hard and
      soft nanolatex spheres. The crack formation is examined as a function of the
      proportion of hard and soft deformable particles, leading to tunable elastic
      properties of the drying film. In our experimental systems, no crack formation
      could be observed below an onset value of the proportion in hard spheres phi
      approximately 0.45 . During the drying process, the mass of films with various
      compositions in hard and soft spheres is measured as a function of time. The
      results suggest that the soft particles undergo deformation that releases the
      internal stresses.

PMID- 19408896
TI  - Gradual photochemical-induced conversion of liquid polydimethylsiloxane layers to
      carbon containing silica coatings by VUV irradiation at 172 nm.
AB  - Thin liquid layers of polydimethylsiloxane (PDMS) were irradiated by VUV light
      under nitrogen atmosphere using a Xe(2)- excimer lamp. The irradiated layers were
      analyzed with infrared reflection absorption spectroscopy (IRRAS) and X-ray
      photoelectron spectroscopy (XPS), showing a gradual photochemical-induced
      conversion of the liquid PDMS to solid SiO(2)-like coatings. IRRAS measurements
      revealed a smooth frequency shift of the maximal absorption band from 1111 to
      1231 cm(-1) with increasing irradiation energy density caused by a gradual shift
      from the asymmetric Si-O stretching vibration of PDMS to the longitudinal optical
      (LO) mode of SiO(2). The shift was found to be dependent on the applied
      irradiation energy density and the O/Si ratio in the film analyzed by XPS
      measurements. The atomic ratio of O/Si increases from 1:1 to about 2.5:1. At the
      same time, the atomic ratio of C/Si decreases from 2:1 down to 1:6.5. Images
      taken by high resolution field emission scanning electron microscopy (FESEM) and
      scanning force microscopy (SFM) show a smooth surface without cracks or pores.
      The controllable coating properties in combination with the possibility for local
      irradiation using masks are promising high potential for the coating technology.

PMID- 19408897
TI  - Mechanical behavior of a supported lipid bilayer under external shear forces.
AB  - Shear forces from a pressure-driven bulk flow in a microfluidic channel can be
      used to induce and control the motion of a supported lipid bilayer (SLB) formed
      on the walls of the channel. We here present a theoretical model that relates the
      experimentally observed drift velocities of an egg yolk phosphatidylcholine (egg
      PC) SLB to the hydrodynamic drag force from the bulk flow, the intermonolayer
      friction coefficient, b, of the bilayer, and the friction coefficient, bls,
      between the lower leaflet of the bilayer and the supporting substrate. The drift
      velocity and diffusivity of the lipids in the SLB were obtained by photobleaching
      a delimited area of fluorescently labeled lipids and subsequently monitoring the
      recovery and convective motion of the bleached spot. A striking observation was
      that the drift velocity of the lipids was observed to be nearly 6 orders of
      magnitude smaller than the bulk velocity at the center of the channel. This
      predicts a value for bls that is at least 25 times as high as predicted by the
      traditional model with the SLB and the support spaced by a homogeneous 1 nm thick
      film of water. In addition, the intermonolayer friction coefficient was estimated
      to 2x10(7) Pa s/m, a value that increased after addition of glycerol to the bulk
      solution. This increase was accompanied by an equal decrease in the lipid
      diffusivity, with both observations indicating an increased viscous drag within
      the bilayer when glycerol was added to the bulk solution.

PMID- 19408898
TI  - In situ time-resolved XAFS studies of metal particle formation by photoreduction
      in polymer solutions.
AB  - Formation mechanisms of metal particles (rhodium (Rh) and palladium (Pd)
      particles) in an aqueous ethanol solution of poly(N-vinyl-2-pyrrolidone) (PVP) by
      photoreduction were investigated by UV-vis, transmission electron microscopy
      (TEM), and in situ X-ray absorption fine structure (in situ XAFS). The average
      diameter of the Rh and Pd particles prepared by the photoreduction was estimated
      from TEM to be 2.2 and 2.0 nm, respectively. In situ energy-dispersive XAFS (in
      situ DXAFS) measurements were performed to investigate the reduction process of
      Rh(III) and Pd(II) aqua chlorocomplexes as well as their particle formation
      process. The reduction rate of these aqua chlorocomplexes could be quantitatively
      evaluated from the change of X-ray absorbance assigned to the contribution of
      metal-chloride bonds in these complexes. The reduction rate of Rh(III) aqua
      chlorocomplexes was found to be slower than that of Pd(II). It was also
      demonstrated that the reduction process of Rh(III) complexes possessed an
      induction period before the onset of Rh particle formation, although the Pd(II)
      complexes displayed no induction period, since the reduction of Pd(II) occurred
      immediately after mixing of an ethanol solution of Pd(II) complexes with aqueous
      PVP solutions.

PMID- 19408895
TI  - Two prion variants of Sup35p have in-register parallel beta-sheet structures,
      independent of hydration.
AB  - The [PSI(+)] prion is a self-propagating amyloid of the Sup35 protein, normally a
      subunit of the translation termination factor, but impaired in this vital
      function when in the amyloid form. The Sup35 N, M, and C domains are the amino
      terminal prion domain, a connecting polar domain, and the essential C-terminal
      domain resembling eukaryotic elongation factor 1alpha respectively. Different
      [PSI(+)] isolates (prion variants) may have distinct biological properties,
      associated with different amyloid structures. Here we use solid state NMR to
      examine the structure of infectious Sup35NM amyloid fibrils of two prion
      variants. We find that both variants have an in-register parallel beta-sheet
      structure, both in the fully hydrated form and in the lyophilized form. Moreover,
      we confirm that some leucine residues in the M domain participate in the in
      register parallel beta-sheet structure. Transmission of the [PSI(+)] prion by
      amyloid fibrils of Sup35NM and transmission of the [URE3] prion by amyloid
      fibrils of recombinant full-length Ure2p are similar whether they have been
      lyophilized or not (wet or dry).

PMID- 19408899
TI  - Structural organization of humic acid in the solid state.
AB  - Studies of the structural organization of humic acid in solution have suggested
      that it is composed of three fractions, two humic acid-like and one lipid-like,
      that have distinct roles in the process of its self-organization. The present
      work extends the study of humic acid's structural organization to the solid state
      by directly comparing its organization with a physical mixture composed of its
      three fractions using differential scanning calorimetry. Comparative measurements
      of the specific heat capacity as a function of temperature reveal differences
      between the original humic acid and the mixture with the same chemical
      composition. These differences provide direct evidence that humic acid's solid
      state structure is more than just a mixture of components and is determined by
      specific interactions between its components. This study indicates that humic
      acid in the solid state has a hierarchical or "structure within a structure"
      architecture. The lower-level structure is determined by the self-assembly of
      amphiphilic components of humic acid with lipids into a nanostructured composite
      material. A higher-level structure is formed by the association of this composite
      material with the nonamphiphilic components of humic acid.

PMID- 19408900
TI  - Modulating retinoid X receptor with a series of (E)-3-[4-hydroxy-3-(3-alkoxy
      5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)phenyl]acrylic acids and
      their 4-alkoxy isomers.
AB  - Rexinoids are ligands for the retinoid X receptor (RXR) that have great promise
      for both the prevention and treatment of cancer and metabolic diseases. In this
      regard, synthetic, functional, and structural investigations into the structure
      activity relationships of derivatives of the potent RXR agonist (E)-3-[3
      (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-4-hydroxyphenyl]acrylic
      acid (CD3254, 9) have been conducted. We recently reported on the
      characterization of a series of C3'-substituted alkyl ether analogues of 9 (10a
      f), which display activities ranging from partial agonists to pure antagonists.
      The importance of the position of the alkoxy side chain for ligand activity has
      been further explored with the synthesis of C4'-substituted analogues (11a-f).
      Here we describe the synthesis of compounds 11a-f, which appear functionally
      different from their isomeric counterparts, as judged from transactivation assays
      and fluorescence anisotropy experiments. We also report on the 2.0 A resolution
      structure of RXR in complex with the parent compound 9, which helps understanding
      of the impact of the alkyl side chain location on ligand activity.

PMID- 19408901
TI  - Solvent-dependent friction force response of poly(ethylenimine)-graft
      poly(ethylene glycol) brushes investigated by atomic force microscopy.
AB  - Lateral and normal forces between a surface-bound, brushlike copolymer,
      poly(ethylenimine)-graft-poly(ethylene glycol) (PEI-g-PEG), and a silica
      colloidal probe were investigated with atomic force microscopy (AFM) and related
      to the relative mass of the solvent absorbed within the polymer as measured with
      the quartz crystal microbalance. PEI-g-PEG was adsorbed onto an oxide-passivated
      silicon wafer through its exposure to physiologically buffered solutions of the
      polymer. Frictional forces were measured between the colloidal probe and the
      substrate by AFM as the polarity of the solvent was systematically varied.
      Reduced friction forces and greater film thicknesses were encountered under
      solvents of higher polarity, which are attributed to the extended conformation of
      the brushlike copolymer under these conditions. Lateral and normal forces
      detected between the colloidal probe and this surface-bound PEI-g-PEG were found
      to be similar under certain solvent conditions to those measured for poly(L
      lysine)-graft-poly(ethylene glycol), a brushlike copolymer with a different
      molecular architecture. To this end, friction force studies of both symmetric and
      asymmetric PEI-g-PEG-coated interfaces served to identify the contributions of
      conformational and bridging effects in the observed tribological behavior.

PMID- 19408902
TI  - General methodology for evaluating the adhesion force of drops and bubbles on
      solid surfaces.
AB  - The shortcomings of the current formulation for calculating the adhesion force
      for drops and bubbles with noncircular contact lines are discussed. A general
      formulation to evaluate the adhesion force due to surface forces is presented.
      Also, a novel methodology, that is, IBAFA, image based adhesion force analysis,
      was developed to allow implementation of the general formulation. IBAFA is based
      on the use of multiple profile images of a drop. The images are analyzed (1) to
      accurately reconstruct the contact line shape, which is analytically represented
      by a Fourier cosine series, and (2) to measure contact angles at multiple
      locations along the contact line and determine the contact angle distribution
      based on a linear piecewise interpolation routine. The contact line shape
      reconstruction procedure was validated with both actual experiments and simulated
      experiments. The procedure for the evaluation of the adhesion force was tested
      using simulated experiments with synthetic drops of known shapes. A comparison
      with current methods showed that simplifying assumptions (e.g., elliptical
      contact line or linear contact angle distribution) used in these methods result
      in errors up to 76% in the estimated adhesion force. However, the drop adhesion
      force evaluated using IBAFA results in small errors on the order of 1%.

PMID- 19408903
TI  - Interaction of blood plasma with antifouling surfaces.
AB  - Nonspecific adsorption of proteins is a crucial problem in the detection of
      analytes in complex biological media by affinity sensors operating with label
      free detection. We modified the gold surface of surface plasmon resonance (SPR)
      sensors with three types of promising antifouling coatings: self-assembled
      monolayers (SAM)s of alkanethiolates terminated with diethylene glycol and
      carboxylic groups, poly(ethylene glycol) (PEG) grafted onto the SAMs, and
      zwitterionic polymer brushes of poly(carboxybetaine methacrylate),
      poly(sulfobetaine methacrylate), and poly(phosphorylcholine methacrylate). Using
      SPR, we compared the efficacy of the coatings to reduce nonspecific adsorption
      from human blood plasma and from single-protein solutions of human serum albumin,
      immunoglobulin G, fibrinogen, and lysozyme. There was no direct relationship
      between values of water contact angles and plasma deposition on the coated
      surfaces. A rather high plasma deposition on SAMs was decreased by grafting PEG
      chains. Fouling on PEG was observed only from plasma fractions containing
      proteins with molecular mass higher than 350 000 Da. The adsorption kinetics from
      plasma collected from different healthy donors differed. Poly(carboxybetaine
      methacrylate) completely prevented the deposition from plasma, but the other more
      hydrophilic zwitterionic polymers prevented single-protein adsorption but did not
      prevent plasma deposition. The results suggest that neither wettability nor
      adsorption of the main plasma proteins was the main indicator of deposition from
      blood plasma.

PMID- 19408905
TI  - Fast surface modification by microwave assisted click reactions on silicon
      substrates.
AB  - Microwave irradiation has been used for the chemical modification of functional
      monolayers on silicon surfaces. The thermal and chemical stability of these
      layers was tested under microwave irradiation to investigate the possibility to
      use this alternative heating process for the surface functionalization of self
      assembled monolayers. The quality and morphology of the monolayers before and
      after microwave irradiation was analyzed by surface-sensitive techniques, such as
      Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM),
      and contact angle measurements. As a model reaction, the 1,3-dipolar
      cycloaddition of organic azides and terminal acetylenes was tested for the
      chemical modification of functional azide monolayers. Low and high molar mass
      compounds modified with an acetylene group were successfully clicked onto the
      surfaces as confirmed by FTIR spectroscopy and AFM investigations. It could be
      verified that the reaction can be performed in reaction times of 5 min, and a
      comparison to conventional heating mechanisms allowed us to conclude that the
      elevated reaction temperatures result in the fast reaction process.

PMID- 19408904
TI  - Structural phase behavior and vibrational spectroscopic studies of
      biofunctionalized CdS nanoparticles.
AB  - Biomodified CdS nanoparticles were synthesized using l-cysteine as a capping
      agent in the colloidal state as a function of pH. The role of pH on the size and
      structure of CdS nanoparticles was investigated in detail. At pH 7.4 and 9.1, X
      ray diffraction spectra of as prepared samples showed the presence of a mixture
      of cubic and hexagonal phases while cubic phase was formed at pH 11.2. A gradual
      transition to the hexagonal phase was observed for refluxed samples at pH 9.1 and
      11.2. Whereas, at pH 7.4, the sample remains in a mixture of cubic and hexagonal
      phase even after refluxing. The particle size of as prepared samples was about 2
      nm, and for refluxed samples the size increased up to 10 nm. The binding of
      cadmium through thiol group is evidenced by infrared spectra. An intense band due
      to C-C-N vibration was observed after 24 h of reflux. The formation of a specific
      molecular cluster determines the growth of a particular phase. Transmission
      electron microscopy (TEM) studies support the X-ray diffraction (XRD) studies and
      exhibit well separated spherical particles while refluxed samples show
      clustering.

PMID- 19408906
TI  - Surface plasmon resonance imaging of polymer microarrays to study protein-polymer
      interactions in high throughput.
AB  - Polymer microarrays provide a high-throughput format in which to assess
      biointerfacial interactions. This endeavor greatly assists with the development
      of advanced biomaterials. In order to increase the scope of this platform
      technology, the development of analytical tools that are compatible with the
      microarray format and are capable of analyzing biomolecular interactions in high
      throughput is needed. Here, we show that surface plasmon resonance imaging (SPRi)
      is such a tool. SPRi enables spatially resolved, surface sensitive, label free,
      real-time analysis of multiple surface-biomolecular interactions in parallel. In
      order to demonstrate this, we first printed phenylazide-modified polymers onto a
      slide coated with a low fouling base polymer. UV irradiation of the slide
      resulted in the cross-linking of the printed polymer spots to the surface. SPRi
      was then employed to study the adsorption and desorption of bovine serum albumin,
      collagen, and fibronectin to these adhesive microarray spots. The spots were also
      incubated with an adherent cell line, enabling insight into the underlying
      mechanisms of cell attachment to the polymers studied. For the system analyzed
      here, electrostatic interactions were shown to dominate cell attachment.

PMID- 19408908
TI  - Computational investigation of the mechanism of addition of singlet carbenes to
      bicyclobutanes.
AB  - Singlet carbenes are known to react with bicyclobutanes to yield 1,4-diene
      products, as in the addition of dichlorocarbene to bicyclobutane to yield 1,1
      dichloro-1,4-pentadiene. At least two mechanisms have been proposed to explain
      this unusual reaction: (1) a concerted process and (2) a stepwise process
      involving a zwitterionic intermediate. Ab initio electronic structure
      calculations have been performed in order to help distinguish between these two
      mechanistic possibilities. In the parent system, the concerted pathway and the
      corresponding transition structure are readily located. On the other hand, the
      hypothesized zwitterionic intermediate does not correspond to a minimum at most
      levels of theory, even in the presence of a polar medium representing the
      solvent. Instead, this structure corresponds to a transition state or, at best,
      an extremely shallow minimum. The two pathways--one unambiguously concerted, the
      other possibly leading through an extremely shallow minimum (intermediate)--have
      very similar barriers and are expected to be competitive. In the substituted
      1,2,2-trimethylbicyclobutane system, five regioisomeric concerted pathways exist
      and lead to four different diene products. Two of these pathways lie well below
      the others in energy, and they alone are expected to play a significant role at
      ordinary temperatures. Of these two pathways, the one calculated to have the
      slightly lower barrier leads to the only product that is reported experimentally.
      In addition, a sixth geometry of approach exists, leading over a transition
      structure of comparable energy to a shallow minimum that corresponds to a
      zwitterionic intermediate. The calculated potential energy surface suggests that
      the reaction can proceed through this intermediate both to the observed diene
      product and to one of the other isomers. It therefore appears that the concerted
      and stepwise mechanisms are competitive in the substituted system. Taken
      together, the calculated pathways and barriers do not adequately account for the
      very pronounced regioselectivity observed experimentally; only modest
      regioselectivity would be predicted at best. Examination of a calculated
      potential energy surface defined over two relevant internal coordinates sheds
      further light on the reaction and suggests that the experimentally observed
      regioselectivity might derive in considerable part from dynamic effects.

PMID- 19408907
TI  - Asymmetric synthesis of neolignans (-)-epi-conocarpan and (+)-conocarpan via
      Rh(II)-catalyzed C-H insertion process and revision of the absolute configuration
      of (-)-epi-conocarpan.
AB  - Catalytic asymmetric synthesis of neolignan natural products (-)-epi-conocarpan
      and (+)-conocarpan has been achieved by exploiting an enantio- and
      diastereoselective intramolecular C-H insertion reaction to construct a cis-2
      aryl-2,3-dihydrobenzofuran ring system as a key step. The C-H insertion reaction
      of 5-bromoaryldiazoacetate catalyzed by Rh(2)(S-PTTEA)(4), a new dirhodium(II)
      carboxylate complex that incorporates N-phthaloyl-(S)-triethylalaninate as chiral
      bridging ligands, provided 2-aryl-5-bromo-3-methoxycarbonyl-2,3-dihydrobenzofuran
      with exceptionally high diastereoselectivity (cis/trans = 97:3) and high
      enantioselectivity for the cis isomer (84% ee).

PMID- 19408909
TI  - Multicomponent reactions of convertible isonitriles.
AB  - A new family of unsaturated isonitriles has been prepared by the base-promoted
      ring-opening of oxazoles, offering an alternative to the conventional formamide
      dehydration route. These compounds undergo the full complement of multicomponent
      reactions for which isonitriles are known and offer the desirable trait of giving
      amide products that readily participate in acyl substitution reactions (hence,
      they are convertible). Moreover, they do not have the objectionable odors for
      which isonitriles are typically known, making them more accessible as reagents
      for organic synthesis. One focus of the work is isonitriles bearing
      perfluorinated alkyl groups that enable the ready separation of such reagents
      from nonfluorinated reaction products using the "light" fluorous method of
      fluorous solid-phase extraction.

PMID- 19408910
TI  - Location of mesoporphyrin in liposomes determined by site-selective fluorescence
      spectroscopy.
AB  - Binding of photosensitizers to target cells is a crucial step during the
      photodynamic effect. Sensitizer distribution is a good indication of whether the
      chemical is a good candidate for perturbing cell membrane integrity. Hence, the
      photophysical properties of porphyrinoid sensitizers in microheterogeneous
      systems such as liposomes are of outstanding interest. Here we present a site
      selective fluorescence study of liposome systems. Monocomponent, small
      unilamellar vesicles formed of different phosphatidylcholines with incorporated
      mesoporphyrin were investigated. The size distribution of liposomes was measured
      by dynamic light scattering after each step of the experiment. On the basis of
      fluorescence line narrowing spectra of mesoporphyrin, the inhomogeneous
      distribution function was determined in order to characterize the photosensitizer
      location. The dual character of the functions revealed two different locations.
      Decomposition of the inhomogeneous distribution functions into Gaussians and the
      analysis of the fit results suggest that one of the locations for mesoporphyrin
      is between the two lipid layers, and the other one is between the hydrocarbon
      chains of the lipid molecules.

PMID- 19408911
TI  - Thermal decomposition of the benzyl radical to fulvenallene (C7H6) + H.
AB  - We show that the benzyl radical decomposes to the C7H6 fragment fulvenallene
      (+H), by first principles/RRKM study. Calculations using G3X heats of formation
      and B3LYP/6-31G(2df,p) structural and vibrational parameters reveal that the
      reaction proceeds predominantly via a cyclopentenyl-allene radical intermediate,
      with an overall activation enthalpy of ca. 85 kcal mol(-1). Elementary rate
      constants are evaluated using Eckart tunneling corrections, with variational
      transition state theory for barrierless C-H bond dissociation in the
      cyclopentenyl-allene radical. Apparent rate constants are obtained as a function
      of temperature and pressure from a time-dependent RRKM study of the multichannel
      multiwell reaction mechanism. At atmospheric pressure we calculate the
      decomposition rate constant to be k [s(-1)] = 5.93 x 10(35)T(-6.099) exp(
      49,180/T); this is in good agreement with experiment, supporting the assertion
      that fulvenallene is the C7H6 product of benzyl decomposition. The benzyl heat of
      formation is evaluated as 50.4 to 52.2 kcal mol(-1), using isodesmic work
      reactions with the G3X theoretical method. Some novel pathways are presented to
      the cyclopentadienyl radical (C5H5) + acetylene (C2H2), which may constitute a
      minor product channel in benzyl decomposition.

PMID- 19408912
TI  - Trace detection of organic compounds in complex sample matrixes by single photon
      ionization ion trap mass spectrometry: real-time detection of security-relevant
      compounds and online analysis of the coffee-roasting process.
AB  - An in-house-built ion trap mass spectrometer combined with a soft ionization
      source has been set up and tested. As ionization source, an electron beam pumped
      vacuum UV (VUV) excimer lamp (EBEL) was used for single-photon ionization. It was
      shown that soft ionization allows the reduction of fragmentation of the target
      analytes and the suppression of most matrix components. Therefore, the
      combination of photon ionization with the tandem mass spectrometry (MS/MS)
      capability of an ion trap yields a powerful tool for molecular ion peak detection
      and identification of organic trace compounds in complex matrixes. This setup was
      successfully tested for two different applications. The first one is the
      detection of security-relevant substances like explosives, narcotics, and
      chemical warfare agents. One test substance from each of these groups was chosen
      and detected successfully with single photon ionization ion trap mass
      spectrometry (SPI-ITMS) MS/MS measurements. Additionally, first tests were
      performed, demonstrating that this method is not influenced by matrix compounds.
      The second field of application is the detection of process gases. Here, exhaust
      gas from coffee roasting was analyzed in real time, and some of its compounds
      were identified using MS/MS studies.

PMID- 19408913
TI  - Propagating fronts in thin tubes: concentration, electric, and pH effects in a
      two-dimensional precipitation pulse system.
AB  - In this paper, we studied the dynamics of a CaCO3 precipitate deposition pulse in
      a thin, long tube connecting two reservoir sinks of coprecipitates. The pulse
      profile, as well as the time t(c) and distance x(c) of the first appearance of
      precipitate, is studied as a function of the initial concentration of CO(3)(2-)
      in the right reservoir, [CO(3)(2-)](0), and later as a function of an applied
      external electric field at different voltages. The time variations of the pulse
      location and the pH at the center of the tube are determined. The distance from
      the calcium chloride sink (x) at any fixed time decreases as [CO(3)(2-)](0)
      increases. The time evolution of the front location exhibits a crossover between
      an early time regime and a late time regime. The pH-time curve shows a marked
      resemblance with a sigmoid shape. At any time, the pH consistently increases with
      [CO(3)(2-)](0). In the presence of a constant electric field applied across the
      tube (fixed voltage), t(c) decreased with the field strength, whereas x(c)
      exhibited a correlated increase. Irregularities in the variation of distance with
      the applied voltage (at a fixed time) were noted. The pH experiences a slight
      increase with the applied voltage. The pulse width exhibits a nonlinear time
      dependence, of the form w = a + bt(1/6). The shape of the deposition pulse
      deviates from a Gaussian distribution. This study is of special interest in the
      experimental simulation and modeling of precipitate deposition and potential
      clogging in microcapillary channels.

PMID- 19408915
TI  - Additivity of the excess energy dissipation rate in a dynamically self-assembled
      system.
AB  - Despite its prevalence in biological systems and its promise as a route to
      adaptive and/or self-healing materials, dynamic self-assembly (DySA) far from
      thermodynamic equilibrium remains poorly understood. In this context, it is
      desirable to develop general thermodynamic relations describing the steady-state
      configurations of such dissipative assemblies. Here, numerical simulations and
      analytical methods are used to calculate the viscous energy dissipation rates in
      a prototypical, magnetohydrodynamic DySA system. In addition to the well
      established criteria of mechanical equilibrium, it is shown that the naturally
      forming steady-state configurations/flows are characterized by a fundamentally
      different relation based on the viscous energy dissipation. Specifically, the
      total dissipation of the n-particle system may be expressed as a sum of pairwise
      "interactions" derived from the analogous two-particle system. This dissipation
      additivity holds despite the presence of many-body forces/torques between the
      particles and may prove useful in estimating the viscosities of colloidal
      suspensions.

PMID- 19408914
TI  - Formation of an intramolecular G-quadruplex of human telomere induced by poly(L
      lysine) under salt-deficient conditions.
AB  - A single-stranded G-tract human telomere DNA sequence is able to fold into
      intramolecular G-quadruplex structures which may be important for a number of
      biological processes and disease-related mechanisms. Poly(L-lysine) (PLL) polymer
      is linear polypeptides with lysine as the repeat unit and has been employed as a
      gene carrier in achieving targeted delivery of DNA to cancer cells. To explore
      the influence of PLL on the conformation of Hum24 DNA, we have investigated the
      interaction of PLL with Hum24 by biophysical methods, mainly CD, ESI-MS, and
      polyacrylamide gel electrophoresis for the first time. The CD data have shown
      that PLL can induce single-stranded Hum24 to form an intramolecular parallel G
      quadruplex structure, further confirmed by ESI-MS analysis and gel
      electrophoresis results. The formation of an intramolecular G-quadruplex is
      strongly dependent on the Hum24/PLL molar ratios and the length of both the
      polypeptides and oligonucleotide. Such phenomena may be interpreted by
      electrostatically attracting negative-charged Hum24 by positive-charged PLL which
      facilitates the close contact between the guanines and formation of hydrogen
      bonding, thus leading the final shape of a G-quadruplex structure.

PMID- 19408916
TI  - Effects of quantum dots in polymerase chain reaction.
AB  - The effects of quantum dots (QDs) on the elimination of nonspecific amplification
      of the polymerase chain reaction (PCR) were investigated. It was found that QDs
      could increase the specificity of the PCR at different annealing temperatures and
      with DNA templates of different lengths. The effects of QDs on the efficiency of
      the PCR were also studied, and the results showed that there was no enhancement.
      The mechanisms underlying these effects are discussed. This method could be used
      to modify the amplification results of the conventional PCR. Furthermore, this
      technology could make the PCR more widely applicable, especially in the multi-PCR
      reaction system with different annealing temperatures. This is of great
      significance for gene diagnosis.

PMID- 19408917
TI  - Absorption of CO2 in the ionic liquid 1-n-hexyl-3-methylimidazolium
      tris(pentafluoroethyl)trifluorophosphate ([hmim][FEP]): a molecular view by
      computer simulations.
AB  - Using a computational screening methodology, we predicted (AIChE J. 2008, 54,
      2717) that the anion tris(pentafluoroethyl)trifluorophosphate ([FEP]) should
      increase the solubility of CO2 in ionic liquids (ILs) relative to a wide range of
      conventional anions. This prediction was confirmed experimentally. In this work,
      we develop a united-atom force field for the [FEP] anion and use the continuous
      fractional component Monte Carlo (CFC MC) method to predict CO2 absorption
      isotherms in 1-n-hexyl-3-methylimidazolium ([hmim]) [FEP] at 298.2 and 323.2 K
      and pressures up to 20.0 bar. The simulated isotherms overestimate the solubility
      of CO2 by about 20% but capture the experimental trends quite well. Additional
      Monte Carlo (MC) and molecular dynamics (MD) simulations are performed to study
      the mechanisms of CO2 absorption in [hmim][FEP] and [hmim][PF6]. The site-site
      radial distribution functions (RDFs) show that CO2 is highly organized around the
      [PF6] anion due to its symmetry and smaller size, while less ordered
      distributions were found around [FEP] and [hmim]. However, more CO2 can be found
      in the first coordination shell of [FEP] compared with [PF6]. The structures of
      ILs, illustrated by P-P radial distribution functions, change very little upon
      the addition of as much as 50 mol % CO2. An energetic analysis shows that the van
      der Waals interactions between CO2 and ILs are generally larger than
      electrostatic interactions.

PMID- 19408918
TI  - What kinds of ferryl species exist for compound II of chloroperoxidase? A dialog
      of theory with experiment.
AB  - QM/MM calculations of Mossbauer parameters lead to assignments of the three
      isomeric species of CPO-II, "major", "minor", and unassigned "6% species", which
      were recently observed in experiment and posed two puzzles (Stone, K. L.;
      Hoffart, L. M.; Behan, R. K.; Krebs, C.; Green, M. T. J. Am. Chem. Soc. 2006,
      128, 6147). Both the minor and major species were found to be iron(IV)
      hydroxides, thus accounting for the observed ratio of their relative yield that
      is pH-independent. The difference between the minor and major species is a single
      water molecule that acts as a H-bond acceptor from the ferryl in the minor
      species (2b) and it is essential to get a good match of the calculated Mossbauer
      parameters to the experimentally observed ones for the minor species. The major
      species (2c-2e, 2e-NW) may or may not have a water molecule. The calculations
      reveal also two candidates for the unassigned 6% species, which are a
      Por+*FeIIIOH species 2e-Fe(III), without or with a water molecule, or the
      corresponding aqua complex Por+*FeIIIOH2 3c formed by adding an additional proton
      to the system. These species have DeltaEQ parameters of the same magnitude but
      with opposite signs: negative (-2.30 mm/s) for the two 2e-Fe(III) species and
      positive (2.39 mm/s) for 3c. The above assignments were further consolidated by
      an extended correlation (Figure 2) between the iron spin density and the DeltaEQ
      parameters of the species calculated in the present study and by relating DeltaEQ
      to the d-electronic configuration on iron. A bonding model of the FeO(H) moiety
      (Figure 3) was used to account for the variation of the spin density and provided
      further support for the correlation in Figure 2 and the assignment. Experimental
      determination of the sign of the quadruple parameter will finally confirm the
      identity of this species. In addition, since 3c possesses an additional proton,
      its identity can be revealed by pH-dependent yield. All in all, the present paper
      shows that QM/MM calculations can conduct a useful dialogue with experiment in
      this complex field.

PMID- 19408919
TI  - Infrared spectroscopic and X-ray studies of the 4-propyl-4'
      isothiocyanatobiphenyl (3TCB).
AB  - The results of mid-infrared spectroscopy and X-ray studies of the third member of
      the 4-n-alkyl-4'-isothiocyanatobiphenyl (nTCB) homologous series are presented.
      Correspondence between the phase transitions observed by means of the IR
      spectroscopy and those given by the adiabatic calorimetry was found. The
      structure of five solid phases was obtained by X-ray measurements. IR
      spectroscopic and X-ray data give the arguments supporting the identification of
      the glass of smectic E phase. Assignment of the IR vibrational bands, in the
      smectic E, in the glass of smectic E, and in one of the crystalline phases, with
      help of the hybrid B3LYP/6-311++G(d,f) functional calculations is presented.

PMID- 19408920
TI  - Solid state photochemistry of novel composites containing luminescent metal
      centers and poly(2-methoxyaniline-5-sulfonic acid).
AB  - Steady state luminescence and measurements of the luminescent lifetime as well as
      cyclic voltammetry have been used to elucidate the mechanism and dynamics of
      interaction between a luminescent ruthenium metal center and two different
      fractions of poly(2-methoxyaniline-5-sulfonic acid) (PMAS). The two fractions,
      high molecular weight (HMWT) PMAS and low molecular weight (LMWT) PMAS oligomer,
      showed significantly distinctive influences on the luminophore. The HMWT PMAS,
      confirmed to be an emeraldine salt by its characteristic redox chemistry, greatly
      impacted the diffusion coefficient of the Ru2+/3+ within the composite film,
      increasing the diffusion coefficient, DCT, by 2 orders of magnitude. The HMWT
      PMAS also resulted in quenching of the ruthenium-based emission. Significantly,
      these results indicate that quenching involves both static and dynamic processes,
      with the static quenching being the dominant process, suggesting that the metal
      center and polymer backbone were strongly associated. In stark contrast, the LMWT
      PMAS did not influence the electrochemical properties of the ruthenium metal
      center; however, it did double the emission observed from the ruthenium metal
      center. The insensitivity of the luminescence lifetime does suggest that, as with
      the HMWT PMAS, LWMT PMAS is strongly associated with the ruthenium metal center.
      The enhanced luminescence may allow for many potential sensor developments based
      on the luminescent ruthenium metal center, while the HMWT PMAS quenching could be
      utilized within quenching-based strategies or electrochemical devices.

PMID- 19408921
TI  - Theoretical study on the structural properties and relative stability of M(II)-Al
      layered double hydroxides based on a cluster model.
AB  - The [M2Al(OH2)9(OH)4]3+ clusters (M = divalent cation Mg2+, Ca2+, Mn2+, Fe2+,
      Co2+, Ni2+, Cu2+, Zn2+, or Cd2+), which include the basic information of layered
      double hydroxides (LDHs) lattice structure with the most economical size, have
      been investigated by density functional theory (DFT) to shed light on the
      structural properties and relative stability of M(II)-Al binary LDHs layers with
      a M2+/Al3+ ratio of 2. The geometric parameters (bond distance and bond angle),
      natural bond orbitals (NBO), stretching vibration frequencies of three-centered
      bridging OH groups (nu(O3-H)), as well as binding energy of the cluster model
      were systematically studied. It was found that the geometries and the nu(O3-H)
      frequency for the calculated clusters are remarkably influenced by the electronic
      structure of the divalent cations, such as valence electronic configuration,
      natural bond orbitals, natural charge transfer, and bond order. The calculated
      binding energies are in good agreement with the relative stability of the
      experimental results for the corresponding LDHs. The calculation results reveal
      that the 2Ni-Al cluster shows the highest stability among the open-shelled cation
      containing clusters, while the stability of the 2Cu-Al cluster is the weakest;
      the 2Mg-Al and 2Zn-Al clusters are the most stable ones among the closed-shelled
      cation-containing clusters. These findings are in high accordance with the
      experimental results. Therefore, this work provides a detailed understanding of
      how the electronic structure of cations plays a more significant role in the
      structural properties and relative stability of the corresponding LDHs layers
      rather than ionic size.

PMID- 19408922
TI  - Donor-dictated interlocking co-complexation reactions of LiNHDipp with
      dimethylzinc: synthesis and structures of new methyl(amido)zincates.
AB  - A systematic study of the interlocking co-complexation reactions between the
      primary lithium amide LiNHDipp (Dipp = 2,6-diisopropylphenyl) and dimethylzinc in
      the presence of different donor ligands is presented which concludes that the
      final outcome of these reactions is largely dictated by the type of structure
      that is formed when the donor is coordinated to the lithium amide. When chelating
      diamine TMEDA (N,N,N',N'-tetramethylethylenediamine) is employed
      [{Li(2)(NHDipp)(2)(TMEDA)}(infinity)] (1) is obtained, where Li(2)N(2) rings are
      connected by TMEDA bridges generating a polymeric chain arrangement which does
      not form a co-complex with Me(2)Zn even in the presence of an excess of TMEDA.
      The tridentate ligand PMDETA (N,N,N',N'',N''-pentamethyldiethylenetriamine) when
      reacted with LiNHDipp forms monomeric [(PMDETA)Li(NHDipp)](4) which successfully
      forms a mixed-metal co-complex with Me(2)Zn affording dialkyl(amido)zincate
      [(PMDETA)LiZn(NHDipp)(Me)(2)] (2). When the co-complexation reaction is carried
      out in the presence of monodentate tetrahydrofuran (THF), zincate
      [(THF)(3)LiZn(NHDipp)(Me)(2)] (3) is obtained which was found to partially
      decompose in hexane solution after long periods of time at room temperature (2
      weeks) to afford the unprecedented "zinc-rich" zincate
      [(THF)(3)LiZn(2)(Me)(3)(NHDipp)(2)] (5). This compound presents a unique
      structure in the solid state previously unknown in organozincate chemistry with a
      trinuclear Li...Zn...Zn chain arrangement where the metals are connected by only
      two amido bridges and therefore both zinc centers exhibit trigonal planar
      geometries. 5 can be prepared in good yields by the rational reaction of LiNHDipp
      with a 2:1:3 mixture of Me(2)Zn, NH(2)Dipp and THF. The different solid-state
      structural motifs of compounds 1, 2, 4, and 5 have been revealed by X-ray
      crystallographic studies. Multinuclear NMR ((1)H, (13)C and (7)Li) spectroscopic
      data recorded in C(6)D(6) solution are also reported for compounds 1-6. Mixed
      metal compounds 2 and 5 constitute the first examples of crystallographically
      characterized alkyl(amido)zincates containing a primary amide.

PMID- 19408923
TI  - Engineering low-aspect ratio carbon nanostructures: nanocups, nanorings, and
      nanocontainers.
AB  - The synthesis of carbon nanostructures, with interesting morphologies, has
      created a revolution in nanotechnology; carbon nanotube is a case in point, but
      other nanoscale morphologies of graphitic carbon could provide compelling uses.
      In particular short structures, including very short nanotubes, have proven
      impossible to be grown by existing techniques due to the difficulty in
      controlling and terminating growth during initial stages. Here we present
      architectures engineered from graphitic carbon, having up to 10(5) times smaller
      length/diameter (L/D) ratios compared to conventional nanotubes, revealing unique
      morphologies of nanocups, nanorings, and large area connected nanocup arrays.
      Such highly engineered hollow nanostructures were fabricated using precisely
      controlled short nanopores inside anodic aluminum oxide templates. The nanocups
      were effectively used to hold and contain other nanomaterials, for example, metal
      nanoparticles, leading to the formation of multicomponent hybrid nanostructures
      with unusual morphologies. The results reported here open up possibilities to
      integrate new morphologies of graphitic carbon in nanotechnology applications.

PMID- 19408925
TI  - Self-assembled double ladder structure formed inside carbon nanotubes by
      encapsulation of H8Si8O12.
AB  - Unique low-dimensional SiO(2)-based nanomaterials can be encapsulated and
      synthesized inside the nanometer-scale one-dimensional internal spaces of carbon
      nanotubes (CNTs). In this study, various single-walled CNTs (SWNTs) and double
      walled CNTs (DWNTs) having different diameters are used as containers for cubic
      octameric H(8)Si(8)O(12) molecules. High-resolution transmission electron
      microscopy (HRTEM), Fourier transform infrared (FT-IR) spectroscopy, and Raman
      spectroscopy observations revealed that, depending on the diameter of the CNTs,
      two types of structures are formed inside the SWNTs and DWNTs: In the case of
      those CNTs having inner diameters ranging from 1.2 to 1.4 nm, a new ordered self
      assembled structure composed of H(8)Si(4n)O(8n-4) molecules was formed through
      the transformation of H(8)Si(8)O(12); however, in the case of CNTs having inner
      diameters larger than 1.7 nm, a disordered structure was formed. This behavior
      may indicate that strong interactions occur between the CNTs and the encapsulated
      H(8)Si(4n)O(8n-4) molecules.

PMID- 19408924
TI  - Functionalized carbon nanotubes specifically bind to alpha-chymotrypsin's
      catalytic site and regulate its enzymatic function.
AB  - Although carbon nanotubes (CNTs) have been shown to nonspecifically bind proteins
      through charge complementary, pi-pi stacking or hydrophobic interactions, they
      have not been shown to bind to a specific site on proteins. By generating surface
      molecular diversity, we created functionalized CNTs that recognize and bind to
      the catalytic site of alpha-chymotrypsin and inhibit its enzymatic activity
      competitively.

PMID- 19408926
TI  - Cu(I)-catalyzed diamination of disubstituted terminal olefins: an approach to
      potent NK1 antagonist.
AB  - This paper describes a diamination process using di-tert-butyldiaziridinone as
      nitrogen source and CuCl as catalyst. A wide variety of disubstituted terminal
      olefins can be efficiently diaminated in good yields under mild condition. This
      diamination process was used to synthesize potent NK(1) antagonist Sch 425078.

PMID- 19408927
TI  - Nanocrystal diffusion in a liquid thin film observed by in situ transmission
      electron microscopy.
AB  - We have directly observed motion of inorganic nanoparticles during fluid
      evaporation using a transmission electron microscope. Tracking real-time
      diffusion of both spherical (5-15 nm) and rod-shaped (5 x 10 nm) gold
      nanocrystals in a thin film of water-15% glycerol reveals complex movements, such
      as rolling motions coupled to large-step movements and macroscopic violations of
      the Stokes-Einstein relation for diffusion. As drying patches form during the
      final stages of evaporation, particle motion is dominated by the nearby
      retracting liquid front.

PMID- 19408928
TI  - Nanoparticle assemblies as memristors.
AB  - Recently a memristor ( Chua, L. O. IEEE Trans. Circuit Theory 1971 , 18 , 507 ),
      the fourth fundamental passive circuit element, has been demonstrated as thin
      film device operations ( Strukov, D. B.; Snider, G. S.; Stewart, D. R.; Williams,
      R. S. Nature (London) 2008 , 453 , 80 ; Yang, J. J.; Pickett. M. D.; Li, X.;
      Ohlberg, D. A. A.; Stewart, D. R.; Williams, R. S. Nat. Nanotechnol. 2008 , 3 ,
      429 ). A new addition to the memristor family can be nanoparticle assemblies
      consisting of an infinite number of monodispersed, crystalline magnetite
      (Fe(3)O(4)) particles. Assembly of nanoparticles that have sizes below 10 nm,
      exhibits at room temperature a voltage-current hysteresis with an abrupt and
      large bipolar resistance switching (R(OFF)/R(ON) approximately 20).
      Interestingly, observed behavior could be interpreted by adopting an extended
      memristor model that combines both a time-dependent resistance and a time
      dependent capacitance. We also observed that such behavior is not restricted to
      magnetites; it is a general property of nanoparticle assemblies as it was
      consistently observed in different types of spinel structured nanoparticles with
      different sizes and compositions. Further investigation into this new
      nanoassembly system will be of importance to the realization of the next
      generation nanodevices with potential advantages of simpler and inexpensive
      device fabrications.

PMID- 19408929
TI  - Soil depth and tillage effects on glyphosate degradation.
AB  - The use of glyphosate-resistant crops facilitated the widespread adoption of no
      tillage (NT) cropping systems. The experimental objectives were to determine
      glyphosate sorption, mineralization, and persistence at two depths [0-2 cm (A)
      and 2-10 cm (B)] in a silt loam managed under long-term conventional tillage (CT)
      or NT soybean. Relative to the other soils, organic carbon (OC) and fluorescein
      diacetate (FDA) hydrolytic activity were at least 1.4-fold higher in NT-A.
      Glyphosate K(d) values ranged from 78.2 to 48.1 and were not correlated with OC.
      Cumulative glyphosate mineralized after 35 days was highest in NT-A soil (70%),
      intermediate in CT-A and CT-B (63%), and least in NT-B (51%). Mineralization was
      positively correlated with OC and FDA activity, but negatively correlated with
      K(d), indicating that sorption decreased bioavailability. Independent of tillage
      and depth, the half-lives for 0.01 N CaCl(2) and 0.1 N NaOH extractable residues
      (bioavailable residues and residues bound to iron and aluminum oxides,
      respectively) were <or=1.2 h and <or=14.2 days, respectively. These data indicate
      that glyphosate sorption and persistence are similar between the surface of NT
      and CT soils and that the adoption of NT will likely have minimal impact on the
      risk for nontarget effects of glyphosate on soil microflora or transport in
      surface runoff.

PMID- 19408932
TI  - Spectroscopy and electronic structures of Ru2(ap)4-alkynyl compounds.
AB  - A new N,N'-bidentate ligand, 2-(3-isobutoxyanilino)pyridine (H(i)BuOap), was
      introduced and used as the ancillary ligand to support highly soluble diruthenium
      compounds. Thus, the new compounds Ru(2)((i)BuOap)(4)Cl (1),
      Ru(2)((i)BuOap)(4)(C[triple bond]CPh) (2), Ru(2)((i)BuOap)(4)(C[triple
      bond]CPh)(2) (3), and Ru(2)((i)BuOap)(4)(C[triple bond]CSi(i)Pr(3)) (4) were
      prepared and characterized by both voltammetric and spectroscopic methods, and
      their physical properties were found to be quite similar to those of the
      previously reported Ru(2)(ap)(4)-based compounds. The spectroscopic properties of
      both anionic and cationic derivatives of compounds 2 and 3 were examined with
      spectroelectrochemistry. Density functional theory calculations performed on
      model compounds of 2 and 3 provide an in-depth picture of the electronic
      structures of Ru(2)(ap)(4)-based alkynyl compounds and assignment of the observed
      electronic transitions.

PMID- 19408931
TI  - Conjugate base of a secondary phosphine selenide [P(Se)(O(i)Pr)2]- as the
      bridging unit for the construction of heterometallic Fe(II)-Hg(II)/Cd(II)
      complexes.
AB  - Reactions of perchlorate salts of Hg(II)/Cd(II) with
      [CpFe(CO)(2)P(Se)(O(i)Pr)(2)] (denoted as L) produced dicationic clusters
      [HgL(2)](ClO(4))(2), 1; [HgL(3)](ClO(4))(2), 2; and [CdL(3)(H(2)O)](ClO(4))(2),
      11. However, the reactions of L with Hg(II)/Cd(II) halides yielded neutral
      complexes. For instance, HgI(2) produced [Hg(3)I(6)L(2)], 3, or [HgI(2)L(2)], 4,
      depending on the metal-to-ligand ratio used. Reaction of L with any of the
      Hg(II)/Cd(II) halides in a 1:1 ratio produced neutral clusters [HgX(mu-X)L](2) (M
      = Hg; X = Cl, 5; Br, 6; I, 7; M = Cd; X = Cl, 8; Br, 9; I, 10). Thus, variation
      of the M-to-L ratio made it possible for the formation of compounds with
      different metal/ligand stoichiometries only when ClO(4)(-) and I(-) salts of
      Hg(II) were used. Single-crystal X-ray crystallography revealed that two and
      three L units were connected to a Hg(II) via its Se atom in 1 and 2,
      respectively, whereas Hg(II) in 4 was connected to two "I" and two "L" units. An
      L (through its Se) and a terminal halogen were attached to each of the Hg(II)'s
      of the Hg(2)X(2) parallelogram core in 5 and 6. The cadmium complex 8, with a
      Cd(2)Cl(2) parallelogram core, was isostructural with the mercury complex 5.
      Although bonding and connectivity in 8 were similar to those in 9 and 10, the
      conformation of the bulky L ligands was unusually syn in 9 and 10, unlike the
      anti orientation in 5, 6, and 8. The syn conformation of L was also observed in
      compounds 1 and 2. Secondary interactions, namely, Se...Se interaction, the X...H
      C type of H-bonding (X = halogen or Se), and pi-stacking, revealed in the
      structures played a role in determining the ligand conformation. The
      [P(Se)(O(i)Pr)(2)](-), the conjugate base of secondary phosphine selenide
      [HP(Se)(O(i)Pr)(2)], acted as a bridge with P bonded to Fe and Se bonded to Hg
      (or Cd) in these heterometallic clusters. Compound 5 further demonstrated a
      longer P-Se bond in the secondary phosphine selenide compared to that in
      isostructural, tertiary phosphine selenide metal complexes.

PMID- 19408933
TI  - Self-assembly of semiconductor organogelator nanowires for photoinduced charge
      separation.
AB  - We investigated an innovative concept of general validity based on an
      organogel/polymer system to generate donor-acceptor nanostructures suitable for
      charge generation and charge transport. An electron conducting (acceptor)
      perylene bisimide organogelator forms nanowires in suitable solvents during
      gelation process. This phenomenon was utilized for its self-assembly in an
      amorphous hole conducting (donor) polymer matrix to realize an interpenetrating
      donor-acceptor interface with inherent morphological stability. The self-assembly
      and interface generation were carried out either stepwise or in a single-step.
      Morphology of the donor-acceptor network in thin films obtained via both routes
      were studied by a combination of scanning electron microscopy and atomic force
      microscopy. Additionally, photoinduced charge separation and charge transport in
      these systems were tested in organic solar cells. Fabrication steps of multilayer
      organogel/polymer photovoltaic devices were optimized with respect to morphology
      and surface roughness by introducing additional smoothening layers and charge
      injection/blocking layers. An inverted cell geometry was used here in which
      electrons are collected at the bottom electrode and holes at the top electrode.
      The simultaneous preparation of the interface exhibits almost 3-fold improvement
      in device characteristics compared to the successive method. The device
      characteristics under AM1.5 spectral conditions and 100 mW/cm(2) for the
      simultaneous preparation route are short circuit current J(sc) = 0.28 mA cm(-2),
      open circuit voltage V(OC) = 390 mV, fill factor FF = 38%, and a power conversion
      efficiency eta = 0.041%.

PMID- 19408934
TI  - Effect of electronic structures of Au clusters stabilized by poly(N-vinyl-2
      pyrrolidone) on aerobic oxidation catalysis.
AB  - Au clusters smaller than 1.5 nm and stabilized by poly(N-vinyl-2-pyrrolidone)
      (PVP) showed higher activity for aerobic oxidation of alcohol than those of
      larger size or stabilized by poly(allylamine) (PAA). X-ray photoelectron
      spectroscopy, Fourier transform infrared spectroscopy of adsorbed CO, and X-ray
      absorption near edge structure measurements revealed that the catalytically
      active Au clusters are negatively charged by electron donation from PVP, and the
      catalytic activity is enhanced with increasing electron density on the Au core.
      Based on similar observations of Au cluster anions in the gas phase, we propose
      that electron transfer from the anionic Au cores of Au:PVP into the LUMO (pi*) of
      O(2) generates superoxo- or peroxo-like species, which plays a key role in the
      oxidation of alcohol. On the basis of these results, a simple principle is
      presented for the synthesis of Au oxidation catalysts stabilized by organic
      molecules.

PMID- 19408938
TI  - Electrokinetics: it's in their genes.
AB  - Work carried out in the Soviet Union 30 years ago by the father-and-son team of
      Stanislav and Andrei Dukhin now has implications in nanotechnology and
      microfluidics.

PMID- 19408937
TI  - Inhibitory effects and molecular mechanism of dieckol isolated from marine brown
      alga on COX-2 and iNOS in microglial cells.
AB  - To identify the neuroprotective effect of dieckol, a hexameric compound of
      phloroglucinol isolated from marine brown alga, Ecklonia cava , this study
      investigated the anti-inflammatory effect of dieckol on lipopolysaccharide (LPS)
      stimulated murine BV2 microglia and elucidated the molecular mechanism. The
      results showed that dieckol suppresses LPS-induced production of nitric oxide
      (NO) and prostaglandin E(2) (PGE(2)) and expression of inducible nitric oxide
      synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner, without
      causing cytotoxicity. It also significantly reduced the generation of
      proinflammatory cytokines, such as interleukin (IL)-1beta and tumor necrosis
      factor (TNF)-alpha. Moreover, dieckol significantly reduced LPS-induced nuclear
      factor kappaB (NF-kappaB) and p38 mitogen-activated protein kinases (MAPKs)
      activation, as well as reactive oxygen species (ROS) production. Taken together,
      the inhibition of LPS-induced NO and PGE(2) production might be due to the
      suppression of NF-kappaB and p38 MAPK signal pathway and, at least in part, by
      inhibiting the generation of ROS. Hence, these effects of dieckol might assist
      therapeutic treatment for neurodegenerative diseases that are accompanied by
      microglial activation.

PMID- 19408939
TI  - Novel reactions of one-electron oxidized radicals of selenomethionine in
      comparison with methionine.
AB  - Pulse radiolysis studies on hydroxyl (*OH) radical reactions of selenomethionine
      (SeM), a selenium analogue of methionine, were carried out, and the resultant
      transient radical cations and their subsequent reactions have been reported. At
      pH<3, the >Se*-OH radical adducts produced on reaction of SeM with *OH radical
      were converted to selenium centered radical cations (Se*+M), which react with
      another molecule of SeM to form dimer radical cation M(Se therefore Se)M+. At pH
      7, the >Se*-OH radical adducts were converted to a monomer radical of the type
      (Se therefore N)M+ that acquires intramolecular stability through interaction
      with the lone pair of the N atom and this radical is denoted as SeM*+. SeM*+
      decayed by first order kinetics, and the reduction potential of the couple
      SeM*+/SeM was determined to be 1.21+/-0.05 V vs NHE at pH 7. SeM*+ oxidized ABTS2
      and TMPD with rate constants of (2.5+/-0.1)x10(8) and (6.1+/-0.2)x10(8) M(-1) s(
      1), respectively, and reacted with hydroxide ion with a rate constant of (3.8+/
      0.9)x10(5) M(-1) s(-1). SeM*+ reacts with molecular oxygen, and the rate constant
      for this reaction was determined to be (4.3+/-0.2)x10(8) M(-1) s(-1); similar
      reaction with methionine could not be observed experimentally. Like methionine
      radical cations, SeM*+ undergoes decarboxylation, although with lesser yield, to
      produce reducing 3-methyl-selenopropyl amino radicals (referred as alpha-amino
      radicals). The formation of these radicals was confirmed both by the estimation
      of the liberated CO2 and by one-electron reduction of MV2+, thionine, and PNAP.
      These results have been supported by quantum chemical calculations. Implications
      of these results in the biological role of SeM have also been briefly discussed.

PMID- 19408940
TI  - Magnetic bead processor for rapid evaluation and optimization of parameters for
      phosphopeptide enrichment.
AB  - Qualitative and quantitative analysis of phosphorylation continues to be both an
      important and a challenging experimental paradigm in proteomics-based research.
      Unfortunately researchers face difficulties inherent to the optimization of
      complex, multivariable methods and their application to the analysis of rare and
      often experimentally intractable phosphorylated peptides. Here we describe a
      platform based on manipulation of magnetic beads in a 96-well format that
      facilitates rapid evaluation of experimental parameters required for enrichment
      of phosphopeptides. Optimized methods provided for automated enrichment and
      subsequent LC-MS/MS detection of over 1000 unique phosphopeptides (approximately
      1% FDR) from 50 microg of cell lysates. In addition we demonstrate use of this
      platform for identification of phosphopeptides derived from proteins separated by
      SDS-PAGE and visualized near the detection limit of silver staining.

PMID- 19408942
TI  - Large pi-aromatic molecules as potential sensitizers for highly efficient dye
      sensitized solar cells.
AB  - Recently, dye-sensitized solar cells have attracted much attention relevant to
      global environmental issues. Thus far, ruthenium(II) bipyridyl complexes have
      proven to be the most efficient TiO(2) sensitizers in dye-sensitized solar cells.
      However, a gradual increment in the highest power conversion efficiency has been
      recognized in the past decade. More importantly, considering that ruthenium is a
      rare metal, novel dyes without metal or using inexpensive metal are desirable for
      highly efficient dye-sensitized solar cells. Large pi-aromatic molecules, such as
      porphyrins, phthalocyanines, and perylenes, are important classes of potential
      sensitizers for highly efficient dye-sensitized solar cells, owing to their
      photostability and high light-harvesting capabilities that can allow applications
      in thinner, low-cost dye-sensitized solar cells. Porphyrins possess an intense
      Soret band at 400 nm and moderate Q bands at 600 nm. Nevertheless, the poor light
      harvesting properties relative to the ruthenium complexes have limited the cell
      performance of porphyrin-sensitized TiO(2) cells. Elongation of the pi
      conjugation and loss of symmetry in porphyrins cause broadening and a red shift
      of the absorption bands together with an increasing intensity of the Q bands
      relative to that of the Soret band. On the basis of the strategy, the cell
      performance of porphyrin-sensitized solar cells has been improved intensively by
      the enhanced light absorption. Actually, some push-pull-type porphyrins have
      disclosed a remarkably high power conversion efficiency (6-7%) that was close to
      that of the ruthenium complexes. Phthalocyanines exhibit strong absorption around
      300 and 700 nm and redox features that are similar to porphyrins. Moreover,
      phthalocyanines are transparent over a large region of the visible spectrum,
      thereby enabling the possibility of using them as "photovoltaic windows".
      However, the cell performance was poor, owing to strong aggregation and lack of
      directionality in the excited state. Novel unsymmetrical zinc phthalocyanine
      sensitizers with "push" and "pull" groups have made it possible to reduce the
      aggregation on a TiO(2) surface, tune the level of the excited state, and
      strengthen the electronic coupling between the phthalocyanine core and the TiO(2)
      surface. As a result, the power conversion efficiency of up to 3.5% has been
      achieved. Perylenes are well-known as chemically, thermally, and photophysically
      stable dyes and have been used in various optical devices and applications.
      Nevertheless, the power conversion efficiency remained low compared to other
      organic dyes. The origin of such limited cell performance is the poor electron
      donating abilities of the perylenes, which makes it difficult to inject electrons
      from the excited singlet state of the perylenes to the conduction band of the
      TiO(2) electrode efficiently. Strongly electron-donating perylene carboxylic acid
      derivatives with amine substituents at their perylene core have allowed us to
      increase the power conversion efficiency of up to approximately 7% in perylene
      sensitized solar cells. The efficiency of large pi-aromatic molecule-sensitized
      solar cells could be improved significantly if the dyes with larger red and near
      infrared absorption could be developed.

PMID- 19408941
TI  - Automated lipid identification and quantification by multidimensional mass
      spectrometry-based shotgun lipidomics.
AB  - This article presents the strategies underlying the automated identification and
      quantification of individual lipid molecular species through array analysis of
      multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) data, which
      are acquired directly from lipid extracts after direct infusion and intrasource
      separation. The automated analyses of individual lipid molecular species in the
      program employ a strategy in which MDMS-SL data from building block analyses
      using precursor ion scans, neutral loss scans, or both are used to identify
      individual molecular species, followed by quantitation. Through this strategy,
      the program screens and identifies species in a high-throughput fashion from a
      built-in database of over 36,000 potential lipid molecular species constructed
      employing known building blocks. The program then uses a two-step procedure for
      quantitation of the identified species possessing a linear dynamic range over 3
      orders of magnitude and reverifies the results when necessary through redundant
      quantification of multidimensional mass spectra. This program is designed to be
      easily adaptable for other shotgun lipidomics approaches that are currently used
      for mass spectrometric analysis of lipids. Accordingly, the development of this
      program should greatly accelerate high-throughput analysis of lipids using MDMS
      based shotgun lipidomics.

PMID- 19408943
TI  - Charge conduction and breakdown mechanisms in self-assembled nanodielectrics.
AB  - Developing alternative high dielectric constant (k) materials for use as gate
      dielectrics is essential for continued advances in conventional inorganic CMOS
      and organic thin film transistors (OTFTs). Thicker films of high-k materials
      suppress tunneling leakage currents while providing effective capacitances
      comparable to those of thin films of lower-k materials. Self-assembled monolayers
      (SAMs) and multilayers offer attractive options for alternative OTFT gate
      dielectrics. One class of materials, organosilane-based self-assembled
      nanodielectrics (SANDs), has been shown to form robust films with excellent
      insulating and surface passivation properties, enhancing both organic and
      inorganic TFT performance and lowering device operating voltages. Since gate
      leakage current through the dielectric is one factor limiting continued TFT
      performance improvements, we investigate here the current (voltage, temperature)
      (I (V,T)) transport characteristics of SAND types II (pi-conjugated layer) and
      III (sigma-saturated + pi-conjugated layers) in Si/native SiO(2)/SAND/Au metal
      insulator-metal (MIS) devices over the temperature range -60 to +100 degrees C.
      It is found that the location of the pi-conjugated layer with respect to the
      Si/SiO(2) substrate surface in combination with a saturated alkylsilane tunneling
      barrier is crucial in controlling the overall leakage current through the various
      SAND structures. For small applied voltages, hopping transport dominates at all
      temperatures for the pi-conjugated system (type II). However, for type III SANDs,
      the sigma- and pi-monolayers dominate the transport in two different transport
      regimes: hopping between +25 degrees C and +100 degrees C, and an apparent switch
      to tunneling for temperatures below 25 degrees C. The sigma-saturated alkylsilane
      tunneling barrier functions to reduce type III current leakage by blocking
      injected electrons, and by enabling bulk-dominated (Poole-Frenkel) transport vs
      electrode-dominated (Schottky) transport in type II SANDs. These observations
      provide insights for designing next-generation self-assembled gate dielectrics,
      since the bulk-dominated transport resulting from combining sigma- and pi-layers
      should enable realization of gate dielectrics with further enhanced performance.

PMID- 19408944
TI  - Hydrogen-bond-assisted epoxidation of homoallylic and allylic alcohols with
      hydrogen peroxide catalyzed by selenium-containing dinuclear peroxotungstate.
AB  - The reaction of peroxotungstates (H(2)WO(4) + H(2)O(2)) with H(2)SeO(4) gave the
      novel selenium-containing dinuclear tungsten species,
      (TBA)(2)[SeO(4){WO(O(2))(2)}(2)] (I, TBA = [(n-C(4)H(9))(4)N](+)), which was
      characterized by elemental analysis, IR, Raman, UV-vis, (77)Se NMR, (183)W NMR,
      and CSI-MS. Various kinds of homoallylic and allylic alcohols were efficiently
      epoxidized to the corresponding epoxy alcohols in high yields with 1 equiv.
      H(2)O(2) with respect to the substrates. Compound I showed the highest catalytic
      activity for H(2)O(2)-based epoxidation of homoallylic and allylic alcohols among
      selenium and tungsten complexes. The turnover frequency reached up to 150 h(-1)
      in a 10 mmol-scale epoxidation of cis-3-hexen-1-ol and this value was the highest
      among those reported for the transition-metal catalyzed epoxidation of
      homoallylic alcohols with H(2)O(2). The kinetic, mechanistic, computational
      studies showed that the stabilization of the transition-state by the hydrogen
      bonding between I and the substrates results in the high reactivity for the I
      catalyzed epoxidation of homoallylic and allylic alcohols. The nature of the
      hetero atoms in the di- and tetranuclear peroxotungstates with XO(4)(n-) ligands
      (X = As(V), P(V), S(VI), Si(IV), etc.) was crucial in controlling the Lewis
      acidity of the peroxotungstates, which significantly affects their electrophilic
      oxygen transfer reactivity. All the data of the structural, kinetic,
      spectroscopic, and computational comparison show that the dimeric peroxotungstate
      unit, {WO(O(2))(2)}(2), in I is activated by the SeO(4)(2-) ligand.

PMID- 19408945
TI  - Microsolvation of cysteine: a density functional theory study.
AB  - Microsolvation of the neutral, zwitterion, and unconventional zwitterion (formed
      by the proton transfer from the thiol to the amine group) was performed using
      PBE1PBE/6-311+G(d,p) calculations. A large sampling of the configurations of the
      clusters involving one to six water molecules was created by analogy to glycine
      clusters and through analysis of hydrogen-bonding trends. Clusters of the neutral
      tautomer are lowest in energy with the inclusion up to five water molecules. With
      six water molecules the neutral and zwitterion are nearly isoenergetic. The
      unconventional zwitterion, while a stable structure when at least one water
      molecule is associated with it, remains energetically noncompetitive with the
      other two tautomers regardless of the degree of microsolvation.

PMID- 19408947
TI  - In situ microarray fabrication and analysis using a microfluidic flow cell array
      integrated with surface plasmon resonance microscopy.
AB  - Surface Plasmon Resonance Microscopy (SPRM) is a promising label-free analytical
      tool for the real-time study of biomolecule interactions in a microarray format.
      However, flow cell design and microarray fabrication have hindered throughput and
      limited applications of SPRM. Here we report the integration of a microfluidic
      flow cell array (MFCA) with SPRM enabling in situ microarray fabrication and
      multichannel analysis of biomolecule probe-target interactions. We demonstrate
      the use of the MFCA for delivery of sample solutions with continuous flow in 24
      channels in parallel for rapid microarray creation and binding analysis while
      using SPRM for real-time monitoring of these processes. Label-free measurement of
      antibody-antibody interactions demonstrates the capabilities of the integrated
      MFCA-SPRM system and establishes the first steps of the development of a high
      throughput, label-free immunogenicity assay. After in situ probe antibody
      immobilization, target antibody binding was monitored in real time in 24 channels
      simultaneously. The limit of detection for this particular antibody pair is 80
      ng/mL which is approximately 6 times lower than the industry recommended
      immunogenicity assay detection limit. The integrated MFCA-SPRM system is a
      powerful and versatile combination for a range of array-based analyses, including
      biomarker screening and drug discovery.

PMID- 19408946
TI  - The myosin C-loop is an allosteric actin contact sensor in actomyosin.
AB  - Actin and myosin form the molecular motor in muscle. Myosin is the enzyme
      performing ATP hydrolysis under the allosteric control of actin such that actin
      binding initiates product release and force generation in the myosin power
      stroke. Non-equilibrium Monte Carlo molecular dynamics simulation of the power
      stroke suggested that a structured surface loop on myosin, the C-loop, is the
      actin contact sensor initiating actin activation of the myosin ATPase. Previous
      experimental work demonstrated C-loop binds actin and established the forward and
      reverse allosteric link between the C-loop and the myosin active site. Here,
      smooth muscle heavy meromyosin C-loop chimeras were constructed with skeletal
      (sCl) and cardiac (cCl) myosin C-loops substituted for the native sequence. In
      both cases, actin-activated ATPase inhibition is indicated mainly by the lower
      V(max). In vitro motility was also inhibited in the chimeras. Motility data were
      collected as a function of myosin surface density, with unregulated actin, and
      with skeletal and cardiac isoforms of tropomyosin-bound actin for the wild type,
      cCl, and sCl. Slow and fast subpopulations of myosin velocities in the wild-type
      species were discovered and represent geometrically unfavorable and favorable
      actomyosin interactions, respectively. Unfavorable interactions are detected at
      all surface densities tested. Favorable interactions are more probable at higher
      myosin surface densities. Cardiac tropomyosin-bound actin promotes the favorable
      actomyosin interactions by lowering the inhibiting geometrical constraint
      barriers with a structural effect on actin. Neither higher surface density nor
      cardiac tropomyosin-bound actin can accelerate motility velocity in cCl or sCl,
      suggesting the element initiating maximal myosin activation by actin resides in
      the C-loop.

PMID- 19408948
TI  - Nanoholes as nanochannels: flow-through plasmonic sensing.
AB  - We combine nanofluidics and nanoplasmonics for surface-plasmon resonance (SPR)
      sensing using flow-through nanohole arrays. The role of surface plasmons on
      resonant transmission motivates the application of nanohole arrays as surface
      based biosensors. Research to date, however, has focused on dead-ended holes, and
      therefore failed to harness the benefits of nanoconfined transport combined with
      SPR sensing. The flow-through format enables rapid transport of reactants to the
      active surface inside the nanoholes, with potential for significantly improved
      time of analysis and biomarker yield through nanohole sieving. We apply the flow
      through method to monitor the formation of a monolayer and the immobilization of
      an ovarian cancer biomarker specific antibody on the sensing surface in real
      time. The flow-through method resulted in a 6-fold improvement in response time
      as compared to the established flow-over method.

PMID- 19408949
TI  - Identification of catalytic Peptide dendrimers by "off-bead" in silica high
      throughput screening of combinatorial libraries.
AB  - A combinatorial library of up to 65'536 peptide dendrimers
      (AcX(8)X(7))(8)(DapX(6)X(5))(4)(DapX(4)X(3))(2)DapX(2)X(1) (Dap = (S)-2,3
      diaminopropionic acid branching point, X(8-1) = groups of four proteinogenic l
      amino acids) was prepared on a photocleavable tentagel resin. The library was
      assayed for catalytic hydrolysis of the fluorogenic substrate 1-butyryloxy-pyrene
      2,7,8-trisulfonate 1 and analogs by a simple procedure involving (a)
      photocleavage from the support in the absence of solvent, (b) spreading of the
      solid support beads on the surface of a silicagel plate impregnated with an
      aqueous buffered substrate solution, and (c) identification of hits as beads
      surrounded by a fluorescent halo indicative of catalysis and sequence
      determination in hits and nonhits by amino acid analysis of the beads. The
      experiment provides direct access to structure-activity relationships in the
      library and delivers active esterase dendrimers. Anionic glutamate residues in
      the outer dendrimer branches were found to inhibit catalysis by histidine
      residues at the dendrimer core. The "off-bead" in silica assay is simple to
      implement and transferable to other library and reaction types.

PMID- 19408951
TI  - Visualizing quantum dots in biological samples using silver staining.
AB  - Quantum dot (QD) based contrast agents are currently being developed as probes
      for bioimaging and as vehicles for drug delivery. The ability to detect QDs,
      regardless of fluorescence brightness, in cells, tissues, and organs is
      imperative to their development. Traditional methods used to visualize the
      distribution of QDs in biological samples mainly rely on fluorescence imaging,
      which does not account for optically degenerate QDs as a result of oxidative
      quenching within the biological environment. Here, we demonstrate the use of
      silver staining for directly visualizing the distribution of QDs within
      biological samples under bright field microscopy. This strategy involves silver
      deposition onto the surface of QDs upon reduction by hydroquinone, effectively
      amplifying the size of QDs until visible for detection. The method can be used to
      detect non-fluorescent QDs and is fast, simple, and inexpensive.

PMID- 19408950
TI  - SAR studies for a new class of antibacterial NAD biosynthesis inhibitors.
AB  - A new lead class of antibacterial drug-like NAD synthetase (NADs) inhibitors was
      previously identified from a virtual screening study. Here a solution-phase
      synthetic library of 76 compounds, analogs of the urea-sulfonamide 5838, was
      synthesized in parallel to explore SAR on the sulfonamide aryl group. All library
      members were tested for enzyme inhibition against NADs and nicotinic acid
      mononucleotide adenylyltransferase (NaMNAT), the last two enzymes in the
      biosynthesis of NAD, and for growth inhibition in a Bacillus anthracis
      antibacterial assay. Most compounds that inhibited bacterial growth also showed
      inhibition against one of the enzymes tested. While only modest enhancements in
      the enzyme inhibition potency against NADs were observed, of significance was the
      observation that the antibacterial urea-sulfonamides more consistently inhibited
      NaMNAT.

PMID- 19408952
TI  - Desiccation induced structural alterations in a 66-amino acid fragment of an
      anhydrobiotic nematode late embryogenesis abundant (LEA) protein.
AB  - Late embryogenesis abundant (LEA) proteins have been found in a number of
      anhydrobiotic (i.e., a state of anhydrobiosis or life without water) organisms
      that are adapted to severe water deficit as a result of extreme drought and cold
      in nature. However, the precise mechanism by which LEA proteins protect the
      organisms in response to water depletion remains to be defined. Because protein
      functions are generally determined by its structure, molecular dynamics
      simulations were performed in this study to understand the structure and its
      stability of a 66-amino acid fragment of a group 3 LEA protein from an
      anhydrobiotic nematode during desiccation. It was found that, unlike the vast
      majority of proteins, the fully hydrated LEA protein in an aqueous solution is by
      and large unstructured (mainly in the form of random coils and turns). The
      protein gradually becomes folded into a hairpin-like, double-bundled, alpha
      helical 3D conformation in response to the loss of water. Major structural
      formation was observed to occur only when the water content is less than about 20
      wt %. It was further found the protein structure and its stability during
      desiccation are determined primarily by hydrogen bonding interactions followed by
      electrostatic interactions, both of which are a result of the extremely
      hydrophilic nature of the LEA protein. The Lennard-Jones interactions (van der
      Waals interactions) are the least important in determining the protein structure
      and its stability during water deficit.

PMID- 19408954
TI  - Organic syntheses and transformations catalyzed by sulfated zirconia.

PMID- 19408953
TI  - Human neutrophil elastase responsive delivery from poly(ethylene glycol)
      hydrogels.
AB  - A novel enzyme-responsive hydrogel drug delivery system was developed with the
      potential to treat inflammation locally. Human neutrophil elastase (HNE) is a
      serine protease secreted by neutrophils which are the first cells recruited to
      inflammatory sites. We exploited this cell-secreted enzyme as a biological cue
      for controlled release. HNE sensitive peptide linkers were immobilized within
      poly(ethylene glycol) hydrogels using photopolymerization techniques. The
      kinetics of the enzyme reaction within the gel was tailored by varying the amino
      acid residues present in the P1 and P1' substrate positions (immediately adjacent
      to cleavage location). A novel FRET-based hydrogel platform was designed to
      characterize the accessibility of the substrate within the cross-linked,
      macroscopic hydrogel. Lastly, a diffusion-reaction mathematical model with
      Michaelis-Menten kinetics was developed to predict the overall release profile
      and captured the initial 80% of the experimentally observed release. The hydrogel
      platform presented shows highly controlled release kinetics with potential
      applications in cellular responsive drug delivery.

PMID- 19408955
TI  - Applicability of standardless semiquantitative analysis of solids by high
      irradiance laser ionization orthogonal time-of-fight mass spectrometry.
AB  - A compact high-irradiance laser ionization time-of-flight mass spectrometry
      system has been developed for the multielemental analysis of solids. Helium was
      introduced into the ion source as a buffer gas to cool high kinetic energy ions
      and suppress the interference of multicharged ions. A special pulse train
      repelling mode was used to achieve explicit spectra. Two quantitative methods are
      described for the laser ionization mass spectrometry in this paper. The first of
      these is the routine calibration curve quantitation, in which various matrix
      matched standards are required; the second method, which is based on the uniform
      correlation between the signal and elemental concentration of different samples,
      is more convenient and covers a typical dynamic range of 6 orders. All the
      investigations and results indicate satisfactory performance of the newly
      developed instrument and its applicability for simultaneous multielemental
      analysis of solid samples.

PMID- 19408956
TI  - Application of fuzzy c-means clustering in data analysis of metabolomics.
AB  - Fuzzy c-means (FCM) clustering is an unsupervised method derived from fuzzy logic
      that is suitable for solving multiclass and ambiguous clustering problems. In
      this study, FCM clustering is applied to cluster metabolomics data. FCM is
      performed directly on the data matrix to generate a membership matrix which
      represents the degree of association the samples have with each cluster. The
      method is parametrized with the number of clusters (C) and the fuzziness
      coefficient (m), which denotes the degree of fuzziness in the algorithm. Both
      have been optimized by combining FCM with partial least-squares (PLS) using the
      membership matrix as the Y matrix in the PLS model. The quality parameters R(2)Y
      and Q(2) of the PLS model have been used to monitor and optimize C and m. Data of
      metabolic profiles from three gene types of Escherichia coli were used to
      demonstrate the method above. Different multivariable analysis methods have been
      compared. Principal component analysis failed to model the metabolite data, while
      partial least-squares discriminant analysis yielded results with overfitting. On
      the basis of the optimized parameters, the FCM was able to reveal main phenotype
      changes and individual characters of three gene types of E. coli. Coupled with
      PLS, FCM provides a powerful research tool for metabolomics with improved
      visualization, accurate classification, and outlier estimation.

PMID- 19408957
TI  - Silver nanocrescents with infrared plasmonic properties as tunable substrates for
      surface enhanced infrared absorption spectroscopy.
AB  - We exploit the unique infrared plasmonic properties of silver nanocrescents
      (AgNCs) in preparing tunable substrates for surface enhanced infrared absorption
      (SEIRA) spectroscopy. Fabrication provides good control over the crescents'
      structural properties which enables tuning of the localized surface plasmon
      resonances (LSPRs) from the visible through the infrared (IR) regions of the
      spectrum. Using AgNCs as uniquely tunable IR LSPR substrates, we demonstrate the
      impact of spectral tuning on maximizing SEIRA signal enhancements measured for
      adsorbed alkylthiolates. The AgNCs demonstrate the largest reported area
      normalized SEIRA signal enhancements which increase from 7,700 to 46,000
      depending on the relative positions of the AgNC's LSPR frequency and the
      molecular vibration frequency. The SEIRA enhancement increases and the absorption
      band line shape becomes more asymmetric as the AgNCs' LSPR frequency overlaps
      more extensively with the frequency of the probed molecular vibration. The
      tunability of the LSPR properties will enable fundamental SEIRA studies and the
      development of optimized SEIRA substrates for detection and identification of
      molecular adsorbates.

PMID- 19408958
TI  - PX- and FYVE-mediated interactions with membranes: simulation studies.
AB  - Molecular dynamics simulations have been used to explore the interactions of two
      PI(3)P-binding domains with their PI ligands and with a phospholipid bilayer.
      Three simulations each of the EEA1-FYVE domain and the p40(phox)-PX domain have
      been compared: with the protein in an apo state, with a bound Ins(1,3)P(2)
      molecule, and bound to a PI(3)P molecule embedded in a lipid bilayer. Two main
      questions were addressed in analysis of the simulations: (i) the location of
      these domains relative to the lipid bilayer and (ii) their interactions with the
      lipids, both specific interactions via bound PI(3)P and nonspecific interactions
      with bilayer phospholipids. Both domains underwent a decrease in dynamic
      flexibility on binding to the ligand and to the membrane, this being more
      pronounced for the FYVE domain. Compared to their starting locations [docked to a
      membrane-inserted PI(3)P molecule], each of the domains penetrated more deeply
      into the lipid bilayer. For FYVE, nonspecific protein-lipid interactions were
      formed mainly by the N-terminal hydrophobic region of the protein. For PX, both
      the alpha1-alpha2 and the beta1-beta2 regions penetrated the bilayer. There
      appeared to be more marked dynamic fluctuations in hydrogen bonds between basic
      side chains and PI(3)P for FYVE than for PX, but for both domains, such
      interactions were maintained throughout the simulations. The simulations agree
      well with available biophysical data, suggesting this computational method may be
      used to predict protein-bilayer interactions for other PI-binding proteins.

PMID- 19408959
TI  - Structure, stability, and folding of ribonuclease H1 from the moderately
      thermophilic Chlorobium tepidum: comparison with thermophilic and mesophilic
      homologues.
AB  - Proteins from thermophilic organisms are able to function under conditions that
      render a typical mesophilic protein inactive. Pairwise comparisons of homologous
      mesophilic and thermophilic proteins can help to identify the energetic features
      of a protein's energy landscape that lead to such thermostability. Previous
      studies of bacterial ribonucleases H (RNases H) from the thermophile Thermus
      thermophilus and the mesophile Escherichia coli revealed that the thermostability
      arises in part from an unusually low change in heat capacity upon unfolding
      (DeltaC(p)) for the thermophilic protein [Hollien, J., and Marqusee, S. (1999)
      Biochemistry 38, 3831-3836]. Here, we have further examined how nearly identical
      proteins can adapt to different thermal constraints by adding a moderately
      thermophilic homologue to the previously characterized mesophilic and
      thermophilic pair. We identified a putative RNase H from Chlorobium. tepidum and
      demonstrated that it is an active RNase H and adopts the RNase H fold. The
      moderately thermophilic protein has a melting temperature (T(m)) similar to that
      of the mesophilic homologue yet also has a surprisingly low DeltaC(p), like the
      thermophilic homologue. This new RNase H folds through a pathway similar to that
      of the previously studied RNases H. These results suggest that lowering the
      DeltaC(p) may be a general strategy for achieving thermophilicity for some
      protein families and implicate the folding core as the major contributor to this
      effect. It should now be possible to design RNases H that display the desired
      thermophilic or mesophilic properties, as defined by their DeltaC(p) values, and
      therefore fine-tune the energy landscape in a predictable fashion.

PMID- 19408960
TI  - Use of pH and kinetic isotope effects to establish chemistry as rate-limiting in
      oxidation of a peptide substrate by LSD1.
AB  - The mechanism of oxidation of a peptide substrate by the flavoprotein lysine
      specific demethylase (LSD1) has been examined using the effects of pH and
      isotopic substitution on steady-state and rapid-reaction kinetic parameters. The
      substrate contained the 21 N-terminal residues of histone H3, with a dimethylated
      lysyl residue at position 4. At pH 7.5, the rate constant for flavin reduction,
      k(red), equals k(cat), establishing the reductive half-reaction as rate-limiting
      at physiological pH. Deuteration of the lysyl methyls results in identical
      kinetic isotope effects of 3.1 +/- 0.2 on the k(red), k(cat), and k(cat)/K(m)
      values for the peptide, establishing C-H bond cleavage as rate-limiting with this
      substrate. No intermediates between oxidized and reduced flavin can be detected
      by stopped-flow spectroscopy, consistent with the expectation for a direct
      hydride transfer mechanism. The k(cat)/K(m) value for the peptide is bell-shaped,
      consistent with a requirement that the nitrogen at the site of oxidation be
      uncharged and that at least one of the other lysyl residues be charged for
      catalysis. The (D)(k(cat)/K(m)) value for the peptide is pH-independent,
      suggesting that the observed value is the intrinsic deuterium kinetic isotope
      effect for oxidation of this substrate.

PMID- 19408961
TI  - Mechanistic variations among reverse transcriptases of simian immunodeficiency
      virus variants isolated from African green monkeys.
AB  - Here we report enzymatic variations among the reverse transcriptases (RTs) of
      five simian immunodeficiency virus (SIV) strains, Sab-1, 155-4, Gri-1, 9063-2,
      and Tan-1, which were isolated from four different species of naturally infected
      African green monkeys living in different regions across Africa. First, Sab-1 RT
      exhibits the most efficient dNTP incorporation efficiency at low dNTP
      concentrations, whereas the other four SIVagm RT proteins display different
      levels of reduced polymerase activity at low dNTP concentrations. Tan-1 RT
      exhibited the most restricted dNTP incorporation efficiency. Indeed, the pre
      steady state analysis revealed that Sab-1 RT displays tight dNTP binding affinity
      (K(d) approximately 1-5 microM), comparable to values observed for NL4-3 and HXB2
      HIV-1 RTs, whereas the dNTP binding affinity of Tan-1 RT is 6.2, approximately
      34.8-fold lower than that of Sab-1 RT. Second, Tan-1 RT fidelity was
      significantly higher than that of Sab-1 RT. Indeed, Tan-1 RT enzymatically mimics
      oncoretroviral murine leukemia virus RT which is characterized by its low dNTP
      binding affinity and high fidelity. This study reports that simultaneous changes
      in dNTP binding affinity and fidelity of RTs appear to occur among natural SIV
      variants isolated from African green monkeys.

PMID- 19408962
TI  - The M17 leucine aminopeptidase of the malaria parasite Plasmodium falciparum:
      importance of active site metal ions in the binding of substrates and inhibitors.
AB  - The M17 leucine aminopeptidase of the intraerythrocytic stages of the malaria
      parasite Plasmodium falciparum (PfLAP) plays a role in releasing amino acids from
      host hemoglobin that are used for parasite protein synthesis, growth, and
      development. This enzyme represents a target at which new antimalarials could be
      designed since metalloaminopeptidase inhibitors prevent the growth of the
      parasites in vitro and in vivo. A study on the metal ion binding characteristics
      of recombinant P. falciparum M17 leucine aminopeptidase (rPfLAP) shows that the
      active site of this exopeptidase contains two metal-binding sites, a readily
      exchangeable site (site 1) and a tight binding site (site 2). The enzyme retains
      activity when the metal ion is removed from site 1, while removal of metal ions
      from both sites results in an inactive apoenzyme that cannot be reactivated by
      the addition of divalent metal cations. The metal ion at site 1 is readily
      exchangeable with several divalent metal ions and displays a preference in the
      order of preference Zn(2+) > Mn(2+) > Co(2+) > Mg(2+). While it is likely that
      native PfLAP contains a Zn(2+) in site 2, the metal ion located in site 1 may be
      dependent on the type and concentration of metal ions in the cytosolic
      compartment of the parasite. Importantly, the type of metal ion present at site 1
      influences not only the catalytic efficiency of the enzyme for peptide substrates
      but also the mode of binding by bestatin, a metal-chelating inhibitor of M17
      aminopeptidases with antimalarial activity.

PMID- 19408963
TI  - Protein profile of capacitated versus ejaculated human sperm.
AB  - Freshly ejaculated sperm acquire the fertilizing potential by a continuing
      process that occurs during sperm transport through the female genital tract, and
      it is physiologically not complete until the spermatozoon reaches the oocyte. The
      process termed capacitation can be mimicked in vitro by using appropriate
      capacitation media. Despite its importance, the molecular mechanisms underlying
      capacitation are poorly understood. This work deals with a proteomic approach to
      the analysis of protein profile variations in human normospermic samples as a
      consequence of three hours in vitro capacitation. 2DE gels were produced per
      freshly ejaculated sperm and per capacitated sperm and several quantitative and
      qualitative significant variations were found. Among the MS obtained
      identifications, proteins with a significant decrease after capacitation were
      found to be involved in protein fate, metabolism, and flagellar organization; on
      the contrary, increasing proteins were found to be related to cellular stress.
      Interestingly, the detected flagellar organization proteins decreased during
      capacitation whereas their corresponding fragments increased. A swim-up selected
      and three-hour capacitated sperm subpopulation has also been resolved by 2DE, and
      its synthetic gel has been analyzed for the variations observed in the entire
      sperm population. An immunofluorescence analysis of this sperm typology was
      carried out with antiactin and antitubulin antibodies.

PMID- 19408964
TI  - Assessing cytochrome P450 and UDP-glucuronosyltransferase contributions to
      warfarin metabolism in humans.
AB  - As a step toward exploring a targeted metabolomics approach to personalized
      warfarin (Coumadin) therapy, we developed a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method capable of quantifying specific enantiomeric (R
      and S) contributions of warfarin (WAR) and the corresponding hydroxywarfarins (OH
      WAR) and glucuronides (-GLUC) generated by cytochrome P450s (CYP) and UDP
      glucuronosyltransferases (UGTs), respectively. Evaluation of quality control
      samples and three commercially available human samples showed that our analytical
      approach has the ability to measure 24 unique WAR metabolites in human urine.
      Evaluation of the human data also provides new insights for evaluating WAR
      toxicity and begins characterizing important UGT metabolic pathways responsible
      for WAR detoxification. Data revealed the significance of specific metabolites
      among patients and the corresponding enzymatic capacity to generate these
      compounds, including the first report of direct WAR glucuronidation. On the basis
      of total OH-WAR levels, (S)-7-OH-WAR was the predominant metabolite indicating
      the significance of CYP2C9 in WAR metabolism, although other CYP2C enzymes also
      contributed to clearance of this isomer. (R)-WAR hydroxylation to OH-WARs was
      more diverse among the patients as reflected in varying contributions of CYP1A2
      and multiple CYP2C enzymes. There was wide variation in the glucuronidation of
      WAR and the OH-WARs with respect to the compounds and patients. 6- and 7-OH-WAR
      were primarily (>70%) excreted as glucuronides unlike 4'-OH-WAR and 8-OH-WAR. For
      all patients, UGT1A1 is likely responsible for 6-O-GLUC production, although
      UGT1A10 may also contribute in one patient. 7-O-GLUC levels reflected
      contributions from potentially five different UGT1A enzymes. In all cases, WAR,
      4'-OH-WAR, 8-OH-WAR, and the corresponding glucuronides were minor metabolites
      with respect to the others. Taken together, these data suggest that both P450 and
      UGT reactions contribute to the generation of excretable products in human urine,
      thereby generating complex metabolic networks.

PMID- 19408965
TI  - HER2 testing to manage patients with breast cancer or other solid tumors.
AB  - OBJECTIVES: Systematic review of trastuzumab outcomes among breast cancer
      patients who have negative, equivocal, or discordant HER2 assay results; use of
      HER2 assay results to predict outcomes of chemotherapy or hormonal therapy
      regimen for breast cancer; use of serum HER2 to monitor treatment response or
      disease progression in breast cancer patients; and use of HER2 testing to manage
      patients with lung, ovarian, prostate, or head and neck tumors. Also, narrative
      review of concordance of HER2 assays. DATA SOURCES: We abstracted data from:
      three articles plus one conference abstract on negative, equivocal, or discordant
      HER2 results; 26 studies on selection of chemotherapy or hormonal therapy; 15
      studies on serum HER2; and 26 studies on ovarian, lung, prostate, or head and
      neck tumors. Foreign-language studies were included. REVIEW METHODS: We sought
      randomized trials or single-arm series (prospective or retrospective) of
      identically treated patients that presented relevant outcome data associated with
      HER2 status. RESULTS: HER2 assay results are influenced by multiple biologic,
      technical, and performance factors. Many aspects of HER2 assays were standardized
      only recently, so inconsistencies confound the literature comparing different
      methods. The evidence is weak on outcomes of trastuzumab added to chemotherapy
      for HER2-equivocal, -discordant, or -negative patients. Evidence comparing
      chemotherapy outcomes in HER2-positive and HER2-negative patient subgroups may
      generate hypotheses, but is too weak to test hypotheses. Only a rigorous test can
      resolve whether HER2-positive patients (but not HER2-negative patients) benefit
      from an anthracycline regimen. Evidence is available only from uncontrolled
      series on whether HER2 status predicts complete pathologic response to
      neoadjuvant chemotherapy. Evidence also is weak regarding differences by HER2
      status for outcomes of chemotherapy for advanced or metastatic disease; with most
      studies lacking statistical power. Data from studies of tamoxifen and aromatase
      inhibitors suggest that future studies should examine whether HER2 status
      predicts response to specific hormonal therapies among estrogen-receptor-positive
      patients. The evidence is weak on whether serum HER2 predicts outcome after
      treatment with any regimens in any setting, as is the evidence on use of serum or
      tissue HER2 testing for malignancies of lung, ovary, head and neck, or prostate.
      CONCLUSIONS: Overall, few studies directly investigated the key questions of this
      systematic review. Going forward, cancer therapy trial protocols should
      incorporate elements to facilitate robust analyses of the use of HER2 status and
      other biomarkers for managing treatment.

PMID- 19408966
TI  - Integration of mental health/substance abuse and primary care.
AB  - OBJECTIVES: To describe models of integrated care used in the United States,
      assess how integration of mental health services into primary care settings or
      primary health care into specialty outpatient settings impacts patient outcomes
      and describe barriers to sustainable programs, use of health information
      technology (IT), and reimbursement structures of integrated care programs within
      the United States. DATA SOURCES: MEDLINE, CINAHL, Cochrane databases, and
      PsychINFO databases, the internet, and expert consultants for relevant trials and
      other literature that does not traditionally appear in peer reviewed journals.
      REVIEW METHODS: Randomized controlled trials and high quality quasi-experimental
      design studies were reviewed for integrated care model design components. For
      trials of mental health services in primary care settings, levels of integration
      codes were constructed and assigned for provider integration, integrated
      processes of care, and their interaction. Forest plots of patient symptom
      severity, treatment response, and remission were constructed to examine
      associations between level of integration and outcomes. RESULTS: Integrated care
      programs have been tested for depression, anxiety, at-risk alcohol, and ADHD in
      primary care settings and for alcohol disorders and persons with severe mental
      illness in specialty care settings. Although most interventions in either setting
      are effective, there is no discernible effect of integration level, processes of
      care, or combination, on patient outcomes for mental health services in primary
      care settings. Organizational and financial barriers persist to successfully
      implement sustainable integrated care programs. Health IT remains a mostly
      undocumented but promising tool. No reimbursement system has been subjected to
      experiment; no evidence exists as to which reimbursement system may most
      effectively support integrated care. Case studies will add to our understanding
      of their implementation and sustainability. CONCLUSIONS: In general, integrated
      care achieved positive outcomes. However, it is not possible to distinguish the
      effects of increased attention to mental health problems from the effects of
      specific strategies, evidenced by the lack of correlation between measures of
      integration or a systematic approach to care processes and the various outcomes.
      Efforts to implement integrated care will have to address financial barriers.
      There is a reasonably strong body of evidence to encourage integrated care, at
      least for depression. Encouragement can include removing obstacles, creating
      incentives, or mandating integrated care. Encouragement will likely differ
      between fee-for-service care and managed care. However, without evidence for a
      clearly superior model, there is legitimate reason to worry about premature
      orthodoxy.

PMID- 19408967
TI  - Effectiveness of weight management programs in children and adolescents.
AB  - OBJECTIVES: To examine available behavioral, pharmacological, and surgical weight
      management interventions for overweight (defined as BMI > 85th to 94th percentile
      of age and sex-specific norms) and/or obese (BMI > 95th percentile) children and
      adolescents in clinical and nonclinical community settings. DATA SOURCES: We
      identified two good quality recent systematic reviews that addressed our research
      questions. We searched Ovid MEDLINE, PsycINFO, Database of Abstracts of Reviews
      of Effects, the Cochrane Database of Systematic Reviews, Cochrane Central
      Register of Controlled Trials, and Education Resources Information Center from
      2005 (2003 for pharmacological studies) to December 11, 2007, to identify
      literature that was published after the search dates of prior relevant systematic
      reviews; we also examined reference lists of five other good-quality systematic
      reviews and of included trials, and considered experts' recommendations. We
      identified two good quality systematic reviews and 2,355 abstracts from which we
      identified 45 primary studies and trials that addressed our research questions.
      REVIEW METHODS: After review by two investigators against pre-determined
      inclusion/exclusion criteria, we included existing good-quality systematic
      reviews, fair-to-good quality trials, and case series (for bariatric surgeries
      only) to evaluate the effects of treatment on weight and weight-related co
      morbidities; we would have included large comparative cohort studies to evaluate
      longer term followup and harms of behavioral and pharmaceutical treatment and
      noncomparative cohort studies for surgical treatments if they had been available.
      Investigators abstracted data into standard evidence tables with abstraction
      checked by a second investigator. Studies were quality-rated by two investigators
      using established criteria. RESULTS: Available research primarily enrolled obese
      (but not overweight) children and adolescents aged 5 to 18 years and no studies
      targeted those less than 5 years of age. Behavioral interventions in schools or
      specialty health care settings can result in small to moderate short-term
      improvements. Absolute or relative weight change associated with behavioral
      interventions in these settings is generally modest and varies by treatment
      intensity and setting. More limited evidence suggests that these improvements can
      be maintained completely (or somewhat) over the 12 months following the end of
      treatments and that there are few harms with behavioral interventions. Two
      medications (sibutramine, orlistat) combined with behavioral interventions can
      result in small to moderate short-term weight loss in obese adolescents with
      potential side effects that range in severity. Among highly selected morbidly
      obese adolescents, very limited data from case series suggest bariatric surgical
      interventions can lead to moderate to substantial weight loss in the short term
      and to some immediate health benefits through resolution of comorbidities, such
      as sleep apnea or asthma. Harms vary by procedure. Short-term severe
      complications are reported in about 5 percent and less severe short-term
      complications occur in 10 to 39 percent. Very few cases provide data to determine
      either beneficial or harmful consequences more than 12 months after surgery.
      CONCLUSIONS: The research evaluating the treatment of obese children and
      adolescents has improved in terms of quality and quantity in the past several
      years. While there are still significant gaps in our understanding of obesity
      treatment in children and adolescents, the current body of research points the
      way to further improvements needed to inform robust policy development.
      Publication of additional research and policy activities by others, including the
      U.S. Preventive Services Task Force, is expected in the near future. And, in
      considering this important public health issue, policymakers should not ignore
      the importance of obesity prevention efforts as well as treatment.

PMID- 19408968
TI  - Barriers and drivers of health information technology use for the elderly,
      chronically ill, and underserved.
AB  - OBJECTIVES: We reviewed the evidence on the barriers and drivers to the use of
      interactive consumer health information technology (health IT) by specific
      populations, namely the elderly, those with chronic conditions or disabilities,
      and the underserved. DATA SOURCES: We searched MEDLINE, CINHAHL, PsycINFO the
      Cochrane Controlled Trials Register and Database of Systematic Reviews, ERIC, and
      the American Association of Retired Persons (AARP) AgeLine databases. We focused
      on literature 1990 to present. METHODS: We included studies of all designs that
      described the direct use of interactive consumer health IT by at least one of the
      populations of interest. We then assessed the quality and abstracted and
      summarized data from these studies with regard to the level of use, the
      usefulness and usability, the barriers and drivers of use, and the effectiveness
      of the interactive consumer health IT applications. RESULTS: We identified and
      reviewed 563 full-text articles and included 129 articles for abstraction. Few of
      the studies were specifically designed to compare the elderly, chronically ill,
      or underserved with the general population. We did find that several types of
      interactive consumer health IT were usable and effective in multiple settings and
      with all of our populations of interest. Of the studies that reported the impact
      of interactive consumer health IT on health outcomes, a consistent finding of our
      review was that these systems tended to have a positive effect when they provided
      a complete feedback loop that included: Monitoring of current patient status.
      Interpretation of this data in light of established, often individualized,
      treatment goals. Adjustment of the management plan as needed. Communication back
      to the patient with tailored recommendations or advice. Repetition of this cycle
      at appropriate intervals. Systems that provided only one or a subset of these
      functions were less consistently effective. The barriers and drivers to use were
      most often reported as secondary outcomes. Many studies were hampered by
      usability problems and unreliable technology, primarily due to the research being
      performed on early stage system prototypes. However, the most common factor
      influencing the successful use of the interactive technology by these specific
      populations was that the consumers' perceived a benefit from using the system.
      Convenience was an important factor. It was critical that data entry not be
      cumbersome and that the intervention fit into the user's daily routine. Usage was
      more successful if the intervention could be delivered on technology consumers
      used every day for other purposes. Finally, rapid and frequent interactions from
      a clinician improved use and user satisfaction. CONCLUSIONS: The systems
      described in the studies we examined depended on the active engagement of
      consumers and patients and the involvement of health professionals, supported by
      the specific technology interventions. Questions remain as to: The optimal
      frequency of use of the system by the patient, which is likely to be condition
      specific. The optimal frequency of use or degree of involvement by health
      professionals. Whether the success depends on repeated modification of the
      patient's treatment regimen or simply ongoing assistance with applying a static
      treatment plan. However, it is clear that the consumer's perception of benefit,
      convenience, and integration into daily activities will serve to facilitate the
      successful use of the interactive technologies for the elderly, chronically ill,
      and underserved.

PMID- 19408969
TI  - Management of chronic hepatitis B.
AB  - OBJECTIVES: Synthesize evidence of the natural history of chronic hepatitis B
      (CHB) and effects and harms of antiviral drugs on clinical, virological,
      histological, and biochemical outcomes. DATA SOURCES: MEDLINE, electronic
      databases, and manual searches of systematic reviews. REVIEW METHODS: We included
      original observational studies to assess natural history and randomized
      controlled trials (RCTs) of adults with CHB published in English to assess
      treatment effects and harms if they reported mortality, incidence of hepato
      cellular carcinoma (HCC), cirrhosis or failure, HBeAg or HBsAg, viral load (HBV
      DNA), alanine aminotransferase (ALT) levels, histological necroinflammatory and
      fibrosis scores, and adverse events after interferon alfa-2b, pegylated
      interferon alfa 2-a, lamivudine, adefovir, entecavir, tenovir or telbivudine. We
      excluded pregnant women, transplant patients, and individuals undergoing cancer
      chemotherapy. We calculated relative risk or absolute risk differences at end of
      treatment and post-treatment. RESULTS: Observational studies (41 publications)
      suggested that male gender, coinfection with hepatitis C, D, or HIV, increased
      HBV DNA, and cirrhosis were associated with increased risk of HCC and death.
      Drugs did not reduce death, liver failure, or HCC in 16 RCTs not designed to test
      long-term clinical outcomes. Evidence from 93 publications of 60 RCTs suggested
      drug effects on viral load or replication, liver enzymes, and histology at end of
      treatment and lasting from 3 to 6 months off treatment. No one treatment improved
      all outcomes and there was limited evidence on comparative effects. Two RCTs
      suggested interferon alfa-2b increased CHB solution versus placebo. Interferon
      alfa-2b or lamivudine improved off treatment HBV DNA and HBeAg clearance and
      seroconversion and ALT normalization. Adefovir improved off treatment ALT
      normalization and HBV DNA clearance. Pegylated interferon alfa 2-a versus
      lamivudine improved off-treatment HBV DNA and HBeAg clearance and seroconversion,
      ALT normalization and liver histology. Lamivudine combined with interferon alfa
      2b versus lamivudine improved off treatment HBV DNA clearance and HBeAg
      seroconversion and reduced HBV DNA mutations. Pegylated interferon alfa 2-a plus
      lamivudine improved off treatment HBV DNA and HBeAg clearance and seroconversion
      and ALT normalization compared to lamivudine but not pegylated interferon alfa 2
      a monotherapy. Adverse events were common but generally mild and did not result
      in increased treatment discontinuation. Longer hepatitis duration, male gender,
      baseline viral load and genotype, HBeAg, and histological status may modify
      treatment effect on intermediate outcomes. Adefovir and pegylated interferon alfa
      2-a with lamivudine improved off treatment viral clearance in HBeAg negative
      patients. There was insufficient evidence to determine if biochemical, viral, or
      histological measures are valid surrogates of treatment effect on mortality,
      liver failure, or cancer. CONCLUSION: Adults with CHB have an increased risk of
      death, hepatic decompensation, and HCC. Mono or combined drug therapy improves
      selected virological, biochemical, and histological markers with no consistent
      effects on all examined outcomes. Patient and disease characteristics may modify
      treatment-induced intermediate outcomes. Evidence was insufficient to assess
      treatment effect on clinical outcomes, predict individualized patient response,
      or determine if intermediate measures are reliable surrogates. Future research
      should assess long-term drug effects on clinical outcomes and among patient
      subpopulations.

PMID- 19408970
TI  - Maternal and neonatal outcomes of elective induction of labor.
AB  - BACKGROUND: Induction of labor is on the rise in the U.S., increasing from 9.5
      percent in 1990 to 22.1 percent in 2004. Although, it is not entirely clear what
      proportion of these inductions are elective (i.e. without a medical indication),
      the overall rate of induction of labor is rising faster than the rate of
      pregnancy complications that would lead to a medically indicated induction.
      However, the maternal and neonatal effects of induction of labor are unclear.
      Many studies compare women with induction of labor to those in spontaneous labor.
      This is problematic, because at any point in the management of the woman with a
      term gestation, the clinician has the choice between induction of labor and
      expectant management, not spontaneous labor. Expectant management of the
      pregnancy involves nonintervention at any particular point in time and allowing
      the pregnancy to progress to a future gestational age. Thus, women undergoing
      expectant management may go into spontaneous labor or may require indicated
      induction of labor at a future gestational age. OBJECTIVES: The Stanford-UCSF
      Evidence-Based Practice Center examined the evidence regarding four Key
      Questions: What evidence describes the maternal risks of elective induction
      versus expectant management? What evidence describes the fetal/neonatal risks of
      elective induction versus expectant management? What is the evidence that certain
      physical conditions/patient characteristics are predictive of a successful
      induction of labor? How is a failed induction defined? METHODS: We performed a
      systematic review to answer the Key Questions. We searched MEDLINE(1966-2007) and
      bibliographies of prior systematic reviews and the included studies for English
      language studies of maternal and fetal outcomes after elective induction of
      labor. We evaluated the quality of included studies. When possible, we
      synthesized study data using random effects models. We also evaluated the
      potential clinical outcomes and cost-effectiveness of elective induction of labor
      versus expectant management of pregnancy labor at 41, 40, and 39 weeks' gestation
      using decision-analytic models. RESULTS: Our searches identified 3,722
      potentially relevant articles, of which 76 articles met inclusion criteria. Nine
      RCTs compared expectant management with elective induction of labor. We found
      that overall, expectant management of pregnancy was associated with an
      approximately 22 percent higher odds of cesarean delivery than elective induction
      of labor (OR 1.22, 95 percent CI 1.07-1.39; absolute risk difference 1.9, 95
      percent CI: 0.2-3.7 percent). The majority of these studies were in women at or
      beyond 41 weeks of gestation (OR 1.21, 95 percent CI 1.01-1.46). In studies of
      women at or beyond 41 weeks of gestation, the evidence was rated as moderate
      because of the size and number of studies and consistency of the findings. Among
      women less than 41 weeks of gestation, there were three trials which reported no
      difference in risk of cesarean delivery among women who were induced as compared
      to expectant management (OR 1.73; 95 percent CI: 0.67-4.5, P=0.26), but all of
      these trials were small, non-U.S., older, and of poor quality. When we stratified
      the analysis by country, we found that the odds of cesarean delivery were higher
      in women who were expectantly managed compared to elective induction of labor in
      studies conducted outside the U.S. (OR 1.22; 95 percent CI 1.05-1.40) but were
      not statistically different in studies conducted in the U.S. (OR 1.28; 95 percent
      CI 0.65-2.49). Women who were expectantly managed were also more likely to have
      meconium-stained amniotic fluid than those who were electively induced (OR 2.04;
      95 percent CI: 1.34-3.09). Observational studies reported a consistently lower
      risk of cesarean delivery among women who underwent spontaneous labor (6 percent)
      compared with women who had an elective induction of labor (8 percent) with a
      statistically significant decrease when combined (OR 0.63; 95 percent CI: 0.49
      0.79), but again utilized the wrong control group and did not appropriately
      adjust for gestational age. We found moderate to high quality evidence that
      increased parity, a more favorable cervical status as assessed by a higher Bishop
      score, and decreased gestational age were associated with successful labor
      induction (58 percent of the included studies defined success as achieving a
      vaginal delivery anytime after the onset of the induction of labor; in these
      instances, induction was considered a failure when it led to a cesarean
      delivery). In the decision analytic model, we utilized a baseline assumption of
      no difference in cesarean delivery between the two arms as there was no
      statistically significant difference in the U.S. studies or in women prior to 41
      0/7 weeks of gestation. In each of the models, women who were electively induced
      had better overall outcomes among both mothers and neonates as estimated by total
      quality-adjusted life years (QALYs) as well as by reduction in specific perinatal
      outcomes such as shoulder dystocia, meconium aspiration syndrome, and
      preeclampsia. Additionally, induction of labor was cost-effective at $10,789 per
      QALY with elective induction of labor at 41 weeks of gestation, $9,932 per QALY
      at 40 weeks of gestation, and $20,222 per QALY at 39 weeks of gestation utilizing
      a cost-effectiveness threshold of $50,000 per QALY. At 41 weeks of gestation,
      these results were generally robust to variations in the assumed ranges in
      univariate and multi-way sensitivity analyses. However, the findings of cost
      effectiveness at 40 and 39 weeks of gestation were not robust to the ranges of
      the assumptions. In addition, the strength of evidence for some model inputs was
      low, therefore our analyses are exploratory rather than definitive. CONCLUSIONS:
      Randomized controlled trials suggest that elective induction of labor at 41 weeks
      of gestation and beyond may be associated with a decrease in both the risk of
      cesarean delivery and of meconium-stained amniotic fluid. The evidence regarding
      elective induction of labor prior to 41 weeks of gestation is insufficient to
      draw any conclusion. There is a paucity of information from prospective RCTs
      examining other maternal or neonatal outcomes in the setting of elective
      induction of labor. Observational studies found higher rates of cesarean delivery
      with elective induction of labor, but compared women undergoing induction of
      labor to women in spontaneous labor and were subject to potential confounding
      bias, particularly from gestational age. Such studies do not inform the question
      of how elective induction of labor affects maternal or neonatal outcomes.
      Elective induction of labor at 41 weeks of gestation and potentially earlier also
      appears to be a cost-effective intervention, but because of the need for further
      data to populate these models our analyses are not definitive. Despite the
      evidence from the prospective, RCTs reported above, there are concerns about the
      translation of such findings into actual practice, thus, there is a great need
      for studying the translation of such research into settings where the majority of
      obstetric care is provided.

PMID- 19408971
TI  - Evaluation of dicloran's contribution to the mutagenic activity of Cristais
      River, Brazil, water samples.
AB  - 2,6-Dichloro-4-nitroaniline (dicloran) is a mutagenic aromatic amine used as an
      agricultural fungicide and in the synthesis of disperse dyes. It is a known
      mutagen (Salmonella/microsome assay) in strains TA98 and TA100. Dicloran was
      initially detected, but not quantified, in the Cristais River, Brazil. The
      objective of the present study was to estimate the contribution of dicloran to
      mutagenic activity in samples from this river. Dicloran was found in the raw
      water at 0.14 microg/L but not in the treated water. Comparison of mutagenic
      potencies in Salmonella strain YG1041 for dicloran and the river water sample
      indicated that dicloran contributed less than 0.1% of total mutagenic activity.

PMID- 19408972
TI  - Equal contribution of increased intracranial pressure and subarachnoid blood to
      cerebral blood flow reduction and receptor upregulation after subarachnoid
      hemorrhage. Laboratory investigation.
AB  - OBJECT: Cerebral ischemia remains the key cause of disability and death in the
      late phase after subarachnoid hemorrhage (SAH), and its pathogenesis is still
      poorly understood. The purpose of this study was to examine whether the change in
      intracranial pressure or the extravasated blood causes the late cerebral ischemia
      and the upregulation of receptors or the cerebral vasoconstriction observed
      following SAH. METHODS: Rats were allocated to 1 of 3 experimental conditions: 1)
      cisternal injection of 250 microl blood (SAH Group), 2) cisternal injection of
      250 microl NaCl (Saline Group), or 3) the same procedure but without fluid
      injection (Sham Group). Two days after the procedure, the basilar and middle
      cerebral arteries were harvested, and contractile responses to endothelin (ET)-1
      and 5-carboxamidotryptamine (5-CT) were investigated by means of myography. In
      addition, real-time polymerase chain reaction was used to determine the mRNA
      levels for ET(A), ET(B), and 5-HT(1) receptors. Regional and global cerebral
      blood flow (CBF) were quantified by means of an autoradiographic technique.
      RESULTS: Compared with the sham condition, both SAH and saline injection resulted
      in significantly enhanced contraction of cerebral arteries in response to ET-1
      and 5-CT. Regional and global CBF were reduced both in the Saline and SAH groups
      compared with the Sham Group. The mRNA levels for ET(B) and 5-HT(1B) receptors
      were upregulated after SAH and saline injection compared with the sham procedure.
      The effects in all parameters were more pronounced for SAH than for saline
      injection. CONCLUSIONS: This study revealed that both the elevation of
      intracranial pressure and subarachnoid blood per se contribute approximately
      equally to the late CBF reductions and receptor upregulation following SAH.

PMID- 19408973
TI  - Impairment of intracerebral arteriole dilation responses after subarachnoid
      hemorrhage. Laboratory investigation.
AB  - OBJECT: Cerebrovascular dysfunction after subarachnoid hemorrhage (SAH) may
      contribute to ischemia, but little is known about the contribution of
      intracerebral arterioles. In this study, the authors tested the hypothesis that
      SAH inhibits the vascular reactivity of intracerebral arterioles and documented
      the time course of this dysfunction. METHODS: Subarachnoid hemorrhage was induced
      using an endovascular filament model in halothane-anesthetized male Sprague
      Dawley rats. Penetrating intracerebral arterioles were harvested 2, 4, 7, or 14
      days postinsult, cannulated using a micropipette system that allowed luminal
      perfusion and control of luminal pressure, and evaluated for reactivity to
      vasodilator agents. RESULTS: Spontaneous tone developed in all pressurized (60 mm
      Hg) intracerebral arterioles harvested in this study (from 66 rats), with similar
      results in the sham and SAH groups. Subarachnoid hemorrhage did not affect
      dilation responses to acidic pH (6.8) but led to a persistent impairment of
      endothelium-dependent dilation responses to adenosine triphosphate (p < 0.01), as
      well as a transient attenuation (p < 0.05) of vascular smooth muscle-dependent
      dilation responses to adenosine, sodium nitroprusside, and 8-Br-cyclic guanosine
      monophosphate (cGMP). Impairment of NO-mediated dilation was more sustained than
      adenosine- and 8-Br-cGMP-induced responses (up to 7 days postinsult compared with
      2 days). All smooth muscle-dependent responses returned to sham levels by 14 days
      after SAH. CONCLUSIONS: Subarachnoid hemorrhage led to a persistent impairment of
      endothelium-dependent dilation and a transient attenuation of vascular smooth
      muscle-dependent dilation responses to adenosine. Impairment of NO-mediated
      dilation occurred when the response to cGMP was intact, suggesting a change in
      cGMP levels rather than an alteration in intracellular mechanisms downstream from
      cGMP.

PMID- 19408974
TI  - Inhibition of 90-kD heat shock protein potentiates the cytotoxicity of
      chemotherapeutic agents in human glioma cells.
AB  - OBJECT: The introduction of temozolomide (TMZ) has advanced chemotherapy for
      malignant gliomas. A considerable number of glioblastoma cases are refractory to
      TMZ, however, and the development of novel chemotherapeutic regimens is needed.
      The authors of previous studies have revealed that hsp90 is expressed at higher
      levels in human neoplastic tissues, including gliomas, than in normal tissues.
      Heat shock protein 90 is involved in a cytoprotective mechanism against cellular
      stressors such as DNA damage, and the authors hypothesized that hsp90 inhibitors
      might act as antitumor agents against gliomas and potentiate the cytotoxicity of
      DNA-damaging agents. METHODS: The authors examined the cytotoxicity of an hsp90
      inhibitor, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), both alone and in
      combination with 1 of 3 DNA-damaging agents (cisplatin, 1,3-bis(2-chloroethyl)-1
      nitrosourea, and TMZ) in human glioma cell lines. The cytotoxicity of these
      agents to glioma cells was measured using a colony formation assay. The cell
      cycle phase distribution, protein expression, and number of apoptotic cells were
      measured using a fluorescence-activated cell sorting assay, immunoblot assays,
      and double staining with annexin V and propidium iodide. In an in vivo
      experiment, 17-AAG, cisplatin, or 17-AAG and cisplatin were administered
      intraperitoneally to mice with xenografted U87MG cells, and the resulting tumor
      volumes were measured. RESULTS: The authors found that 17-AAG reduced the
      clonogenicity of U87MG cells, and at a low concentration (< 100 nM) potentiated
      the cytotoxicity of the DNA-crosslinking agents cisplatin and 1,3-bis(2
      chloroethyl)-1-nitrosourea, but not that of the DNA-methylating agent TMZ. This
      17-AAG-induced potentiation of DNA crosslinking agent-induced cytotoxicity was a
      consequence of prolonged G(2)-M arrest accompanied by the suppression of cdc2 and
      cdc25C and of increased apoptotic cell death accompanied by the degradation of
      the antiapoptosis proteins Akt and survivin. Similar effects were observed when
      cells were treated with radicicol, another hsp90 inhibitor. The 17-AAG-induced
      enhancement of DNA crosslinking agent-induced cytotoxicity was also observed in
      other cell lines. In addition, 17-AAG sensitized xenografted U87MG cells to
      cisplatin in nude mice. CONCLUSIONS: Heat shock protein 90-targeted therapy may
      be an effective strategy for potentiating chemotherapy using DNA-crosslinking
      agents for TMZ-refractory gliomas.

PMID- 19408975
TI  - Failure rate of contemporary low-dose radiosurgical technique for vestibular
      schwannoma.
AB  - OBJECT: The decline in cranial nerve morbidity after radiosurgery for vestibular
      schwannoma (VS) correlates with dose reduction and other technical changes to
      this procedure. The effect these changes have had on tumor control has not been
      well documented. METHODS: The authors performed a retrospective review of 293
      patients with VSs who underwent radiosurgery between 1990 and 2004 and had a
      minimum of 24 months of imaging follow-up (90% of the entire series). The median
      radiation dose to the tumor margin was 13 Gy. Treatment failure was defined as
      progressive tumor enlargement noted on 2 or more imaging studies. The mean
      postradiosurgical follow-up was 60.9 +/- 32.5 months. RESULTS: Tumor growth was
      noted in 15 patients (5%) at a median of 32 months after radiosurgery.
      Radiographically demonstrated tumor control was 96% at 3 years and 94% at 7 years
      after radiosurgery. Univariate analysis revealed 2 factors that correlated with
      failed radiosurgery for VS: an increasing number of isocenters (p = 0.03) and
      tumor margin radiation doses <or= 13 Gy (p = 0.02). Multivariate analysis showed
      that only an increasing number of isocenters correlated with failed VS
      radiosurgery (hazard ratio 1.1, 95% CI 1.02-1.32, p < 0.05). The tumor margin
      radiation dose (p = 0.22) was not associated with tumor growth after
      radiosurgery. CONCLUSIONS: Distortion of stereotactic MR imaging coupled with
      increased radiosurgical conformality and progressive dose reduction likely caused
      some VSs to receive less than the prescribed radiation dose to the entire tumor
      volume.

PMID- 19408976
TI  - Seizure outcome of epilepsy surgery in focal epilepsies associated with
      temporomesial glioneuronal tumors: lesionectomy compared with tailored resection.
AB  - OBJECT: The authors retrospectively analyzed and compared seizure outcome in a
      series of 28 patients with temporomesial glioneuronal tumors associated with
      epilepsy who underwent 1 of 2 different epilepsy surgery procedures: lesionectomy
      or tailored resection. METHODS: The 28 patients were divided into 2 groups, with
      14 cases in each group. In Group A, surgery was limited to the tumor
      (lesionectomy), whereas Group B patients underwent tailored resection involving
      removal of the tumor and the epileptogenic zone as identified by a
      neurophysiological noninvasive presurgical study. RESULTS: In Group A (10 male
      and 4 female patients) the interval between onset of seizures and surgery ranged
      from 1 to 33 years (mean 10.6 years). Patients' ages ranged from 3 to 61 years
      (mean 23.1 years). The epileptogenic lesion was on the left side in 6 patients
      and the right in 8 patients. Mean follow-up was 9.8 years (range 6.5-15 years).
      The Engel classification system, used to determine postoperative seizure outcome,
      showed 6 patients (42.8%) were Engel Class I and 8 (57.1%) were Engel Class II.
      In Group B (6 male and 8 female patients) the interval between onset of seizures
      and surgery ranged from 0.5 to 25 years (mean 8.6 years). Patients' ages ranged
      from 3 to 48 years (mean 22.3 years). The tumor and associated epileptogenic area
      was on the right side in 8 patients and the left in 6 patients. Mean follow-up
      duration was 3.5 years (range 1-6.5 years). Postoperative seizure outcome was
      Engel Class I in 13 patients (93%) and Engel Class II in 1 (7.1%). CONCLUSIONS:
      The authors' results demonstrate a better seizure outcome for temporomesial
      glioneuronal tumors associated with epilepsy in patients who underwent tailored
      resection rather than simple lesionectomy (p = 0.005). For temporomesial
      glioneuronal tumors associated with epilepsy, performing a presurgical
      noninvasive neurophysiological study intended to identify the epileptogenic zone
      is necessary for planning a tailored surgery. Using this surgical strategy, the
      presence of temporomesial glioneuronal tumors constitutes a predictive factor of
      excellent seizure outcome, and therefore surgical treatment can be offered early
      to avoid both the consequences of uncontrolled seizures as well as the side
      effects of pharmacological therapy.

PMID- 19408977
TI  - A new expandable cannula system for endoscopic evacuation of intraparenchymal
      hemorrhages.
AB  - The authors describe a newly developed expandable cannula to enable a more
      efficient use of an endoscope in removing intraparenchymal spontaneous
      hypertensive intracerebral hematomas. The cannula is introduced like a
      conventional brain cannula, using neuronavigation techniques to reach the
      targeted hematoma accurately, and, once deployed, conventional microsurgical
      techniques are used under direct endoscopic visualization. This method was used
      in 6 patients, and, based on the results of intraoperative intracranial pressure
      monitoring and postoperative CT scanning, the authors were able to achieve good
      hematoma removal. They found that by using the expandable cannula, efficient
      endoscopic surgery in the brain parenchyma was possible.

PMID- 19408978
TI  - Microstimulation-induced inhibition as a tool to aid targeting the ventral border
      of the subthalamic nucleus.
AB  - OBJECT: The aim of the current study was to examine and compare the aftereffects
      of local high-frequency microstimulation through the recording electrode on the
      firing of neurons in the subthalamic nucleus (STN) and the substantia nigra pars
      reticulata (SNr) in patients undergoing surgery for deep brain stimulation. Deep
      brain stimulation has been playing an increasing role in the treatment of
      Parkinson disease, with the subthalamic nucleus (STN) being the preferred
      implantation target. Changes in cellular activity indicative of the borders of
      the STN are typically used during surgery to determine the extent of the STN and
      locate the optimal target, but in some cases borders may be difficult to
      identify. In this study the authors compared the effects of microstimulation in
      the SNr and STN. In previous studies they have shown that microstimulation in the
      internal globus pallidus, which is functionally similar to the SNr, inhibits
      firing, whereas similar microstimulation in the STN has minimal effect. The
      presence of inhibition in the SNr but not in the STN could be used as an
      additional criterion to help identify the location of the border between the STN
      and SNr. METHODS: Dual microelectrode recordings were performed during
      stereotactic surgery in 4 patients. Well-isolated high-amplitude units were
      stimulated extracellularly through the recording microelectrode with 0.5-second
      trains of high frequency (200 Hz) and low current (<or= 5 microA). RESULTS: In
      the majority (92%) of SNr neurons, this type of stimulation led to a period of
      inhibition lasting several hundreds of milliseconds following the end of the
      train. In contrast, only 1 neuron of 70 judged to be in the STN by other criteria
      was inhibited by this type of microstimulation, and this neuron was located at
      the ventral border of the STN. CONCLUSIONS: These findings indicate that
      prolonged inhibition of firing following low-amplitude high-frequency
      microstimulation via the recording electrode is a consistent feature of almost
      all SNr neurons and rarely if ever occurs in STN neurons. This feature therefore
      provides a useful additional finding that can be used to help identify the border
      between the STN and SNr.

PMID- 19408979
TI  - Neurosurgical management of intracranial lesions in the pregnant patient: a 36
      year institutional experience and review of the literature.
AB  - OBJECT: A review of the literature has revealed scant data related to
      neurosurgical treatment of gravid patients. The authors reviewed their experience
      with the neurosurgical treatment of pregnant women to better characterize the
      optimal management strategies for intracranial pathological entities in this
      population. METHODS: Between July 1969 and July 2005, 34 patients with documented
      pregnancy and concomitant intracranial pathological entities were treated at the
      authors' institution. The average age of the gravid patients at presentation was
      27 +/- 6 years. Twelve patients harbored vascular and 14 patients harbored
      neoplastic lesions. Four gravid patients suffered from traumatic intracranial
      hemorrhage, 2 had primary intracerebral hemorrhage, and 2 had hydrocephalus. The
      medical records of these patients were reviewed to assess the outcome for the
      mothers and fetuses. RESULTS: Nineteen pregnant patients (56%) underwent a
      neurosurgical procedure after induction of general anesthesia. Of these, 14 (74%)
      underwent craniotomies for clipping/resection of their lesion, 2 (10%) underwent
      stereotactic biopsies, and 3 (16%) underwent CSF shunting procedures. Three
      patients (9%) delivered by cesarean section followed by their neurosurgical
      procedure, and 5 (15%) underwent therapeutic abortion preoperatively to allow for
      radiation therapy early in their pregnancy (4 of these patients underwent surgery
      prior to their therapeutic abortion). Eleven patients (32%) were treated
      nonoperatively while pregnant, and 3 of these received their treatment after
      delivery. There was no operative maternal mortality or permanent morbidity. The
      fetuses did not suffer from any complications related to the mother's
      neurosurgical procedure. CONCLUSIONS: Based on the authors' experience and a
      review of the literature, surgery for intracranial lesions in pregnant patients
      is generally well tolerated by both mother and fetus. Preoperative delivery by
      cesarean section of term or near-term babies is reasonable. Some patients treated
      conservatively may deteriorate and require an operation.

PMID- 19408980
TI  - Comparing the risks of frameless stereotactic biopsy in eloquent and noneloquent
      regions of the brain: a retrospective review of 284 cases.
AB  - OBJECT: Frameless stereotactic biopsy has been shown in multiple studies to be a
      safe and effective tool for the diagnosis of brain lesions. However, no study has
      directly evaluated its safety in lesions located in eloquent regions in
      comparison with noneloquent locations. In this study, the authors determine
      whether an increased risk of neurological decline is associated with biopsy of
      lesions in eloquent regions of the brain. METHODS: Medical records, including
      imaging studies, were reviewed for 284 cases in which frameless stereotactic
      biopsy procedures were performed by 19 neurosurgeons at 7 institutions between
      January 2000 and December 2006. Lesion location was classified as eloquent or
      noneloquent in each patient. The incidence of neurological decline was calculated
      for each group. RESULTS: During the study period, 160 of the 284 biopsies
      predominately involved eloquent regions of the brain. In evaluation of the
      complication rate with respect to biopsy site, neurological decline occurred in 9
      (5.6%) of 160 biopsies in eloquent brain areas and 10 (8.1%) of 124 biopsies in
      noneloquent regions; this difference was not statistically significant (p =
      0.416). A higher number of needle passes was associated with the presence of a
      postoperative hemorrhage at the biopsy site, although not with a change in the
      result of neurological examination. CONCLUSIONS: Frameless stereotactic biopsy of
      lesions located in eloquent brain regions is as safe and effective as biopsy of
      lesions in noneloquent regions. Therefore, with careful planning, frameless
      stereotactic biopsy remains a valuable and safe tool for diagnosis of brain
      lesions, independent of lesion location.

PMID- 19408981
TI  - Secondary gliosarcoma: a review of clinical features and pathological diagnosis.
AB  - OBJECT: Although secondary gliosarcoma after treatment of primary glioblastoma
      multiforme has been described, little is known of these rare tumors. In this
      article the authors review the literature on secondary gliosarcoma, with
      attention to clinical course and pathological features. METHODS: A PubMed search
      of the key word intracranial "gliosarcoma" with and without "radiation" or
      "radiotherapy" in humans was performed. The 204 citations yielded were screened
      for relevancy to gliosarcomas that occur after treatment of previous intracranial
      neoplasms. RESULTS: A search of the literature yielded 24 relevant articles,
      combined for a total of only 12 cases of secondary gliosarcoma and 12 cases of
      radiation-induced gliosarcoma. Of the 12 cases of secondary gliosarcoma, all were
      previously treated with surgery and radiotherapy (mean dose 50.7 Gy), with a mean
      survival of 13 months since time of gliosarcoma diagnosis (range 6.9-19.4
      months). In the cases of radiation-induced gliosarcoma, the mean dose of previous
      radiotherapy was 51.3 Gy (median 54 Gy, range 24-60 Gy), and the mean survival
      since gliosarcoma diagnosis was 6.7 months (median 6 months, range 2-10 months).
      CONCLUSIONS: Secondary gliosarcoma and radiation-induced gliosarcoma are
      exceedingly rare. The literature on secondary gliosarcoma illustrates a more
      favorable survival than for primary gliosarcoma but remains limited regarding
      clinical and radiographic presentation, response to treatment, and pathogenesis.
      The results of the present review also support the notion that secondary
      gliosarcomas and radiation-induced gliosarcomas are distinct entities, with
      longer survival and shorter latency of gliosarcoma induction seen in the former.
      Efforts to elucidate the role of radiotherapy in the induction of gliosarcomas
      may yield new insights into therapeutic risks of cranial radiation and CNS tumor
      pathogenesis.

PMID- 19408982
TI  - Intraventricular cerebral cavernomas: a series of 12 patients and review of the
      literature.
AB  - OBJECT: Intraventricular cavernomas (IVCs) occur in only 2-10% of patients with
      cerebral cavernomas. Reports concerning IVC are scarce and are limited mostly to
      sporadic case reports. In this paper, the authors present a series of 12 patients
      with IVCs that were treated at a single neurosurgical department. In addition,
      the authors reviewed the literature. METHODS: All clinical data were analyzed
      retrospectively. Follow-up questionnaires were sent to all patients. Outcome was
      assessed using the Glasgow Outcome Scale. The authors also conducted a PubMed
      search and found 77 cases of IVC. RESULTS: The patients' median age was 47 years,
      and the male/female ratio was 2:1. A cavernoma occurred in the lateral ventricle
      in 6 patients, in another 5 it was in the fourth ventricle, and 1 had a lesion in
      the third ventricle. Almost all patients presented with acute headache on
      admission and in more than half, the symptoms were related to cavernoma bleeding.
      In total, 8 rebleedings occurred in 5 patients during a median of 0.4 years.
      Three patients with a cavernoma of the fourth ventricle presented with a cranial
      nerve deficit. In 8 cases, a cavernoma was surgically treated an average of 1.3
      years after the diagnosis. Only 1 patient underwent surgery in the acute phase
      after a major intraventricular/intracerebral hemorrhage. The median follow-up
      time was 2 years. No patient was lost to follow-up, and no patient died. In
      total, on follow-up 9 patients improved and 3 had a persistent neurological
      deficit, of which 2 existed before surgery. CONCLUSIONS: In the present series,
      the IVCs had a high tendency for rehemorrhage. Surgery is advocated when
      hemorrhages are frequent, and the mass effect causes progressive neurological
      deficits. Microsurgical removal of the IVC is safe, but in the fourth ventricle
      it can carry increased risk for cranial nerve deficits.

PMID- 19408983
TI  - Frontal-to-temporal horn shunt as treatment for temporal horn entrapment.
AB  - In cases of temporal horn entrapment caused by primary malignant central nervous
      system tumors, the goal is to restore physiological flow of cerebrospinal fluid
      (CSF) while preventing the spread of malignant tumor cells to distant sites. This
      goal is usually accomplished by placement of a traditional ventriculoperitoneal,
      ventriculopleural, or ventriculoatrial shunt. In this study, the authors describe
      a novel treatment approach using placement of a frontal-to-temporal horn shunt as
      an alternative to distal CSF diversion. Stereotactic surgery was used for
      placement of frontal-to-temporal horn shunts in 3 patients who presented with
      focal compressive symptoms caused by temporal horn dilation. Serial imaging
      studies confirmed temporal horn decompression with symptom resolution after a
      maximum of 20 months of follow-up (minimum 2 months in 1 patient who died of
      tumor progression). The authors believe this simple technique may be considered
      for use in all patients with neurological symptoms resulting from temporal horn
      dilation caused by malignant central nervous system neoplasms in which seeding of
      distant sites by CSF diversion is a concern.

PMID- 19408984
TI  - Overdrainage of cerebrospinal fluid caused by detachment of the pressure control
      cam in a programmable valve after 3-tesla magnetic resonance imaging.
AB  - The authors report a rare case of overdrainage of the CSF caused by the
      malfunction of a Codman-Hakim programmable valve (CHPV) following a 3-T MR
      imaging procedure. Nine years ago this 72-year-old woman underwent
      ventriculoperitoneal shunt placement with a CHPV system for hydrocephalus due to
      subarachnoid hemorrhage. The postoperative course was uneventful and the system
      functioned well. A radiograph obtained immediately after 3-T MR imaging revealed
      that the pressure control cam in the valve system was detached from the base
      plate. Intracranial hypotension syndrome occurred several hours after the MR
      imaging study, and a CT scan revealed a decrease in ventricle size. A revision of
      the system promptly resolved the symptoms, and a postoperative CT scan revealed
      that the ventricle size was restored to normal. Examination of the extracted
      valve showed a Y-shaped crack in the plastic housing as well as detachment of the
      white marker and cam from the base plate. A reduction in the power of the flat
      spring to press the valve ball led to CSF overdrainage because of a loss of
      support by the cam. Because the patient had incurred no head injury during the
      day and radiographic studies of the system 5 years previously had shown
      detachment of the white marker, damage to the system might have been caused by a
      past impact. These facts may indicate that the antimagnetic performance of the
      system could have decreased due to a previous impact and that the strong magnetic
      force in a 3-T MR imaging environment might have caused detachment of the cam.

PMID- 19408985
TI  - Edema formation in the hyperacute phase of ischemic stroke. Laboratory
      investigation.
AB  - OBJECT: Brain edema formation is a serious complication of ischemic stroke and
      can lead to mechanical compression of adjacent brain structures, cerebral
      herniation, and death. Furthermore, the space-occupying effect of edema impairs
      regional cerebral blood flow (rCBF), which is particularly important in the
      penumbra phase of stroke. In the present study, the authors evaluated the natural
      course of edema formation in the hyperacute phase of focal cerebral ischemia.
      METHODS: Middle cerebral artery occlusion (MCAO) or a sham procedure was
      performed in rats within an MR imaging unit (in-bore occlusion). Both pre- and
      postischemic images could be compared on a pixel-by-pixel basis. The T2
      relaxation time (T2RT), a marker for brain water content, was measured in regions
      of interest. RESULTS: A significant increase in the T2RT was detectable as early
      as 20-45 minutes after MCAO. At this early time point the midline shift (MLS)
      amounted to 0.214 +/- 0.092 cm in the MCAO group and 0.061 +/- 0.063 cm in the
      sham group (p < 0.007). The T2RT and MLS increased linearly thereafter. Evans
      blue dye was intravenously injected in additional animals 20 and 155 minutes
      after MCAO. Extravasation of the dye was visible in all animals, indicating
      increased permeability of the blood-brain barrier. CONCLUSIONS: Vasogenic brain
      edema occurs much earlier than expected following permanent MCAO and leads to MLS
      and mechanical compression of adjacent brain structures. Since compression
      effects can impair rCBF, early edema formation can significantly contribute to
      infarct formation and thus represents a promising target for neuroprotection.

PMID- 19408987
TI  - Introduction: vascular neurosurgery.

PMID- 19408986
TI  - Extended transsphenoidal approach for pituitary adenomas invading the anterior
      cranial base, cavernous sinus, and clivus: a single-center experience with 126
      consecutive cases.
AB  - OBJECT: The standard transsphenoidal approach has been successfully used to
      resect most pituitary adenomas. However, as a result of the limited exposure
      provided by this procedure, complete surgical removal of pituitary adenomas with
      parasellar or retrosellar extension remains problematic. By additional bone
      removal of the cranial base, the extended transsphenoidal approach provides
      better exposure to the parasellar and clival region compared with the standard
      approach. The authors describe their surgical experience with the extended
      transsphenoidal approach to remove pituitary adenomas invading the anterior
      cranial base, cavernous sinus (CS), and clivus. METHODS: Retrospective analysis
      was performed in 126 patients with pituitary adenomas that were surgically
      treated via the extended transsphenoidal approach between September 1999 and
      March 2008. There were 55 male and 71 female patients with a mean age of 43.4
      years (range 12-75 years). There were 82 cases of macroadenoma and 44 cases of
      giant adenoma. RESULTS: Gross-total resection was achieved in 78 patients
      (61.9%), subtotal resection in 43 (34.1%), and partial resection in 5 (4%).
      Postoperative complications included transient cerebrospinal rhinorrhea (7
      cases), incomplete cranial nerve palsy (5), panhypopituitarism (5), internal
      carotid artery injury (2), monocular blindness (2), permanent diabetes insipidus
      (1), and perforation of the nasal septum (2). No intraoperative or postoperative
      death was observed. CONCLUSIONS: The extended transsphenoidal approach provides
      excellent exposure to pituitary adenomas invading the anterior cranial base, CS,
      and clivus. This approach enhances the degree of tumor resection and keeps
      postoperative complications relatively low. However, radical resection of tumors
      that are firm, highly invasive to the CS, or invading multidirectionally remains
      a big challenge. This procedure not only allows better visualization of the tumor
      and the neurovascular structures but also provides significant working space
      under the microscope, which facilitates intraoperative manipulation. Preoperative
      imaging studies and new techniques such as the neuronavigation system and the
      endoscope improve the efficacy and safety of tumor resection.

PMID- 19408988
TI  - Cerebral arteriovenous malformations. Part 1: cellular and molecular biology.
AB  - OBJECT: The scientific understanding of the nature of arteriovenous malformations
      (AVMs) in the brain is evolving. It is clear from current work that AVMs can
      undergo a variety of phenomena, including growth, remodeling, and/or regression
      and the responsible processes are both molecular and physiological. A review of
      these complex processes is critical to directing future therapeutic approaches.
      The authors performed a comprehensive review of the literature to evaluate
      current information regarding the genetics, pathophysiology, and behavior of
      AVMs. METHODS: A comprehensive literature review was conducted using PubMed to
      reveal the molecular biology of AVMs as it relates to their complex growth and
      behavior patterns. RESULTS: Growth factors involved in AVMs include vascular
      endothelial growth factor, fibroblast growth factor, transforming growth factor
      beta, angiopoietins, fibronectin, laminin, integrin, and matrix
      metalloproteinases. Conclusions Understanding the complicated molecular milieu of
      developing AVMs is essential for defining their natural history. Growth factors,
      extracellular matrix proteins, and other molecular markers will be the key to
      unlocking novel targeted drug treatments for these brain malformations.

PMID- 19408989
TI  - Cerebral arteriovenous malformations. Part 2: physiology.
AB  - OBJECT: The scientific understanding of the nature of arteriovenous malformations
      (AVMs) in the brain is evolving. It is clear from current work that AVMs can
      undergo a variety of phenomena, including growth, remodeling, and/or regression
      and the responsible processes are both molecular and physiological. A review of
      these complex processes is critical to directing future therapeutic approaches.
      The authors performed a comprehensive review of the literature to evaluate
      current information regarding the genetics, pathophysiology, and behavior of
      AVMs. METHODS: A comprehensive literature review was conducted using PubMed to
      reveal the angioarchitecture and cerebral hemodynamics of AVMS as they relate to
      lesion development. RESULTS: Feeding artery pressures, brain AVM
      compartmentalization, venous drainage, flow phenomena, and vascular steal are
      discussed. CONCLUSIONS: The dynamic nature of brain AVMs is at least in part
      attributable to hemodynamic and flow-related phenomena. These forces acting on an
      evolving structure are critical to understanding the challenges in endovascular
      and surgical therapy. As knowledge in this field continues to progress, the
      natural history and predicted behavior of these AVMs will become more clearly
      elucidated.

PMID- 19408991
TI  - Time-of-flight magnetic resonance angiography imaging of a residual arteriovenous
      malformation nidus after Onyx embolization for stereotactic radiosurgery
      planning. Technical note.
AB  - This report demonstrates that time-of-flight (TOF) MR angiography is a useful
      adjunct for planning stereotactic radiosurgery (SRS) of large arteriovenous
      malformations (AVMs) after staged embolization with Onyx. Onyx (ethylene vinyl
      copolymer), a recently approved liquid embolic agent, has been increasingly used
      to exclude portions of large AVMs from the parent circulation prior to SRS.
      Limiting SRS to regions of persistent arteriovenous shunting and excluding
      regions eliminated by embolization may reduce unnecessary radiation doses to
      eloquent brain structures. However, SRS dosimetry planning presents unique
      challenges after Onyx embolization because it creates extensive artifacts on CT
      scans, and it cannot be delineated from untreated nidus on standard MR sequences.
      During the radiosurgery procedure, MR images were obtained using a GE Signa 1.5-T
      unit. Standard axial T2 fast spin echo high-resolution images (TR 3000 msec, TE
      108 msec, slice thickness 2.5 mm) were generated for optimal visualization of
      brain tissue and AVM flow voids. The 3D TOF MR angiography images of the circle
      of Willis and vertebral arteries were subsequently obtained to visualize AVM
      regions embolized with Onyx (TR 37 msec, TE 6.9 msec, flip angle 20 degrees).
      Adjunct TOF MR angiography images demonstrated excellent contrast between nidus
      embolized with Onyx and regions of persistent arteriovenous shunting within a
      large AVM prior to SRS. Additional information derived from these sequences
      resulted in substantial adjustments to the treatment plan and an overall
      reduction in the treated tissue volume.

PMID- 19408990
TI  - Posterior fossa arteriovenous malformations.
AB  - Arteriovenous malformations (AVMs) of the posterior fossa are complex
      neurovascular lesions that are less common than their supratentorial
      counterparts, accounting for < 15% of all AVMs. The majority of patients with
      these lesions present with intracranial hemorrhage, a factor that has been
      consistently shown to increase one's risk for subsequent bleeding. Studies have
      additionally shown a posterior fossa or deep AVM location to portend a more
      aggressive natural history. The authors reviewed the literature on posterior
      fossa AVMs, finding their annual rupture rates to be as high as 11.6%, an
      important factor that underscores the importance of aggressive treatment of
      lesions amenable to intervention as therapeutic options and results continue to
      improve.

PMID- 19408992
TI  - Cranial dural arteriovenous fistulas: modification of angiographic classification
      scales based on new natural history data.
AB  - This article presents a modification to the existing classification scales of
      intracranial dural arteriovenous fistulas based on newly published research
      regarding the relationship of clinical symptoms and outcome. The 2 commonly used
      scales, the Borden-Shucart and Cognard scales, rely entirely on angiographic
      features for categorization. The most critical anatomical feature is the
      identification of cortical venous drainage (CVD; Borden-Shucart Types II and III
      and Cognard Types IIb, IIa + b, III, IV, and V), as this feature identifies
      lesions at high risk for future hemorrhage or ischemic neurological injury. Yet
      recent data has emerged indicating that within these high-risk groups, most of
      the risk for future injury is in the subgroup presenting with intracerebral
      hemorrhage or nonhemorrhagic neurological deficits. The authors have defined this
      subgroup as symptomatic CVD. Patients who present incidentally or with symptoms
      of pulsatile tinnitus or ophthalmological phenomena have a less aggressive
      clinical course. The authors have defined this subgroup as asymptomatic CVD.
      Based on recent data the annual rate of intracerebral hemorrhage is 7.4-7.6% for
      patients with symptomatic CVD compared with 1.4-1.5% for those with asymptomatic
      CVD. The addition of asymptomatic CVD or symptomatic CVD as modifiers to the
      Borden-Shucart and Cognard systems improves their accuracy for risk
      stratification of patients with high-grade dural arteriovenous fistulas.

PMID- 19408993
TI  - Endovascular management of spinal dural arteriovenous fistulas. A review.
AB  - OBJECT: Spinal dural arteriovenous fistulas (DAVFs) are the most common spinal
      vascular malformations and can be a significant cause of myelopathy, yet remain
      inefficiently diagnosed lesions. Over the last several decades, the treatment of
      spinal DAVFs has improved tremendously due to improvements in neuroimaging,
      microsurgical, and endovascular techniques. The aim of this paper was to review
      the existing literature regarding the clinical characteristics, classification,
      and endovascular management of spinal DAVFs. METHODS: A search of the PubMed
      database from the National Library of Medicine and reference lists of all
      relevant articles was conducted to identify all studies pertaining to spinal
      DAVFs, spinal dural fistulas, and spinal vascular malformations, with particular
      attention to endovascular management and outcomes. RESULTS: The ability to
      definitively treat spinal DAVFs using endovascular embolization has significantly
      improved over the last several decades. Overall rates of definitive embolization
      of spinal DAVFs have ranged between 25 and 100%, depending in part on the embolic
      agent used and the use of variable stiffness microcatheters. The majority of
      recent studies in which N-butyl cyanoacrylate or other liquid embolic agents were
      used have reported success rates of 70-90%. Surgical treatment remains the
      definitive option in cases of failed embolization, repeated recanalization, or
      lesions not amenable to embolization. Clinical outcomes have been comparable to
      surgical treatment when the fistula and draining vein remain persistently
      occluded. Improvements in gait and motor function are more likely following
      successful treatment, whereas micturition symptoms are less likely to improve.
      CONCLUSIONS: Endovascular embolization is an increasingly effective therapy in
      the treatment of spinal DAVFs, and can be used as a definitive intervention in
      the majority of patients that undergo modern endovascular intervention. A
      multidisciplinary approach to the treatment of these lesions is required, as
      surgery is required for refractory cases or those not amenable to embolization.
      Newer embolic agents, such as Onyx, hold significant promise for future therapy,
      yet long-term follow-up studies are required.

PMID- 19408994
TI  - Radiosurgery for angiographically occult vascular malformations.
AB  - The use of radiosurgery for angiographically occult vascular malformations
      (AOVMs) is a controversial treatment option for those that are surgically
      inaccessible or located in eloquent brain. To determine the efficacy of this
      treatment, the authors reviewed the literature reporting hemorrhage rates,
      seizure control, and radiation-induced morbidity. They found overall hemorrhage
      rates of 2-6.4%, overall postradiosurgery hemorrhage rates of 1.6-8%, and
      stratified postradiosurgery hemorrhage rates of 7.3-22.4% in the period
      immediately to 2 years after treatment; these latter rates declined to 0.8-5.2% >
      2 years after treatment. Of 291 patients presenting with seizure across 16
      studies, 89 (31%) attained a seizure-free status and 102 (35%) had a reduction in
      seizure frequency after radiosurgery. Overall radiation-induced morbidity ranged
      from 2.5 to 59%, with higher complication rates in patients with brainstem lesion
      locations. Researchers applying mean radiation doses of 15-16.2 Gy to the tumor
      margin saw both low radiation-induced complication rates (0-9.1%) and adequate
      hemorrhage control (0.8-5.2% > 2 years after treatment), whereas mean doses >or=
      16.5 Gy were associated with higher total radiation-induced morbidity rates (>
      17%). Although the use of stereotactic radiosurgery remains controversial,
      patients with AOVMs located in surgically inaccessible areas of the brain may
      benefit from such treatment.

PMID- 19408995
TI  - The evolution of cerebral revascularization surgery.
AB  - Among the relatively few surgeons to be awarded the Nobel Prize was Alexis
      Carrel, a French surgeon and pioneer in revascularization surgery at the turn of
      the 20th century. The authors trace the humble beginnings of cerebral
      revascularization surgery through to the major developments that helped shape the
      modern practice of cerebral bypass surgery. They discuss the cornerstone studies
      in the development of this technique, including the Extracranial/Intracranial
      Bypass Study initiated in 1977. Recent innovations, including modern techniques
      to monitor cerebral blood flow, microanastomosis techniques, and ongoing trials
      that play an important role in the evolution of this field are also evaluated.

PMID- 19408996
TI  - Graft selection in cerebral revascularization.
AB  - Cerebral revascularization constitutes an important treatment modality in the
      management of complex aneurysms, carotid occlusion, tumor, and moyamoya disease.
      Graft selection is a critical step in the planning of revascularization surgery,
      and depends on an understanding of graft and regional hemodynamics,
      accessibility, and patency rates. The goal of this review is to highlight some of
      these properties.

PMID- 19408997
TI  - Operative nuances of an occipital artery to posterior inferior cerebellar artery
      bypass.
AB  - Occipital artery to posterior inferior cerebellar artery bypasses remain an
      important tool for cerebrovascular neurosurgeons, particularly in the management
      of complex aneurysms of the posterior inferior cerebellar artery requiring
      proximal occlusion or trapping. The procedure requires meticulous technique and
      attention to detail. The authors outline their technique for accomplishing this
      bypass emphasizing nuances for complication avoidance.

PMID- 19408998
TI  - Unruptured intracranial aneurysms and the assessment of rupture risk based on
      anatomical and morphological factors: sifting through the sands of data.
AB  - Aneurysmal subarachnoid hemorrhage continues to have high rates of morbidity and
      mortality for patients despite optimal medical and surgical management. Due to
      the fact that aneurysmal rupture can be such a catastrophic event, preventive
      treatment is desirable for high-risk lesions. Given the variability of the
      literature evaluating unruptured aneurysms regarding basic patient population,
      clinical practice, and aneurysm characteristics studied, such as size, location,
      aspect ratio, relationship to the surrounding vasculature, and the aneurysm
      hemodynamics, a meta-analysis is nearly impossible to perform. This review will
      instead focus on the various anatomical and morphological characteristics of
      aneurysms reported in the literature with an attempt to draw broad inferences and
      serve to highlight pressing questions for the future in our continued effort to
      improve clinical management of unruptured intracranial aneurysms.

PMID- 19408999
TI  - Minimally invasive superficial temporal artery to middle cerebral artery bypass
      through a minicraniotomy: benefit of three-dimensional virtual reality planning
      using magnetic resonance angiography.
AB  - OBJECT: The aim of the authors in this study was to introduce a minimally
      invasive superficial temporal artery to middle cerebral artery (STA-MCA) bypass
      surgery by the preselection of appropriate donor and recipient branches in a 3D
      virtual reality setting based on 3-T MR angiography data. METHODS: An STA-MCA
      anastomosis was performed in each of 5 patients. Before surgery, 3-T MR imaging
      was performed with 3D magnetization-prepared rapid acquisition gradient echo
      sequences, and a high-resolution CT 3D dataset was obtained. Image fusion and the
      construction of a 3D virtual reality model of each patient were completed.
      RESULTS: In the 3D virtual reality setting, the skin surface, skull surface, and
      extra- and intracranial arteries as well as the cortical brain surface could be
      displayed in detail. The surgical approach was successfully visualized in virtual
      reality. The anatomical relationship of structures of interest could be evaluated
      based on different values of translucency in all cases. The closest point of the
      appropriate donor branch of the STA and the most suitable recipient M(3) or M(4)
      segment could be calculated with high accuracy preoperatively and determined as
      the center point of the following minicraniotomy. Localization of the craniotomy
      and the skin incision on top of the STA branch was calculated with the system,
      and these data were transferred onto the patient's skin before surgery. In all
      cases the preselected arteries could be found intraoperatively in exact agreement
      with the preoperative planning data. Successful extracranial-intracranial bypass
      surgery was achieved without stereotactic neuronavigation via a preselected
      minimally invasive approach in all cases. Subsequent enlargement of the
      craniotomy was not necessary. Perioperative complications were not observed. All
      bypasses remained patent on follow-up. CONCLUSIONS: With the application of a 3D
      virtual reality planning system, the extent of skin incision and tissue trauma as
      well as the size of the bone flap was minimal. The closest point of the
      appropriate donor branch of the STA and the most suitable recipient M(3) or M(4)
      segment could be preoperatively determined with high accuracy so that the STA-MCA
      bypass could be safely and effectively performed through an optimally located
      minicraniotomy with a mean diameter of 22 mm without the need for stereotactic
      guidance.

PMID- 19409000
TI  - Clinical course of nontraumatic, nonaneurysmal subarachnoid hemorrhage: a single
      institution experience.
AB  - OBJECT: Angiogram-negative subarachnoid hemorrhage (SAH) accounts for 15% of
      nontraumatic SAH and has been reported with low morbidity and mortality rates. We
      report on a large series of patients with angiogram-negative SAH who experienced
      an atypical nonbenign clinical course. METHODS: Between December 2001 and
      November 2006, 95 patients with spontaneous nonaneurysmal SAH and negative
      initial angiographic evaluation were treated at the University of Florida. The
      authors retrospectively reviewed the patients' medical records and radiological
      images to determine associated morbidity and mortality. RESULTS: Aneurysms were
      found in 6 of the 95 patients on follow-up imaging after an initial negative
      angiogram (6.3% false negative rate); these patients were excluded leaving 89
      patients as the study group. Hydrocephalus necessitating temporary CSF diversion
      developed in 22 of these patients (25%); 12 (13%) ultimately required permanent
      CSF diversion. Clinically significant vasospasm developed in 4 patients (4%), and
      2 (2%) had cerebral infarctions. Three patients (3%) died. CONCLUSIONS: The
      authors' experience with a large series of angiogram-negative SAH patients who
      had an atypical nonbenign clinical course associated with hydrocephalus,
      vasospasm, stroke, and mortality differs significantly from previously published
      case series of angiogram-negative SAH.

PMID- 19409001
TI  - Serum and cerebrospinal fluid C-reactive protein levels as predictors of
      vasospasm in aneurysmal subarachnoid hemorrhage. Clinical article.
AB  - OBJECT: Cerebral vasospasm is a common and potentially devastating complication
      of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes seem to play
      a major role in the pathogenesis of vasospasm. The C-reactive protein (CRP)
      constitutes a highly sensitive inflammatory marker. The association of elevated
      systemic CRP and coronary vasospasm has been well established. Additionally,
      elevation of the serum CRP levels has been demonstrated in patients with aSAH.
      The purpose of the current study was to evaluate the possible relationship
      between elevated CRP levels in the serum and CSF and the development of vasospasm
      in patients with aSAH. METHODS: A total of 41 adult patients in whom aSAH was
      diagnosed were included in the study. Their demographics, the admitting Glasgow
      Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, CT scans, digital
      subtraction angiography studies, and daily neurological examinations were
      recorded. Serial serum and CSF CRP measurements were obtained on Days 0, 1, 2, 3,
      5, 7, and 9. All patients underwent either surgical or endovascular treatment
      within 48 hours of their admission. The outcome was evaluated using the Glasgow
      Outcome Scale and the modified Rankin Scale. RESULTS: The CRP levels in serum and
      CSF peaked on the 3rd postadmission day, and the CRP levels in CSF were always
      higher than the serum levels. Patients with lower admission GCS scores and higher
      Hunt and Hess and Fisher grades had statistically significantly higher levels of
      CRP in serum and CSF. Patients with angiographic vasospasm had higher CRP
      measurements in serum and CSF, in a statistically significant fashion (p <
      0.0001). Additionally, patients with higher CRP levels in serum and CSF had less
      favorable outcome in this cohort. CONCLUSIONS: Patients with aSAH who had high
      Hunt and Hess and Fisher grades and low GCS scores showed elevated CRP levels in
      their CSF and serum. Furthermore, patients developing angiographically proven
      vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and
      increased CRP measurements were strongly associated with poor clinical outcome in
      this cohort.

PMID- 19409003
TI  - Intraoperative hypothermia during vascular neurosurgical procedures.
AB  - Increasing evidence in animal models and clinical trials for stroke, hypoxic
      encephalopathy for children, and traumatic brain injury have shown that mild
      hypothermia may attenuate ischemic damage and improve neurological outcome.
      However, it is less clear if mild intraoperative hypothermia during vascular
      neurosurgical procedures results in improved outcomes for patients. This review
      examines the scientific evidence behind hypothermia as a treatment and discusses
      factors that may be important for the use of this adjuvant technique, including
      cooling temperature, duration of hypothermia, and rate of rewarming.

PMID- 19409002
TI  - Delayed stenosis as a consequence of angioplasty for subarachnoid hemorrhage
      induced vasospasm. Case report.
AB  - The authors report a case of restenosis in the bilateral internal carotid
      arteries (ICAs) following angioplasty for cerebral vasospasm. This 53-year-old
      woman suffering subarachnoid hemorrhage due to a ruptured posterior communicating
      artery aneurysm had severe vasospasm and underwent angioplasty of the left and
      right ICAs and middle cerebral arteries. Two months later, a follow-up CT
      angiogram revealed bilateral ICA stenoses. Transluminal angioplasty leads to long
      term connective tissue damage in the medial and adventitial layers from the
      disruption of the arrangement of collagen fibers due to stretching and tearing,
      resulting in loss of transmission of contractile forces. Furthermore, following
      endothelial cell denudation and stretching and rupture of internal elastic lamina
      from angioplasty, reendothelialization of the intimal layer composed of smooth
      muscle cells may also explain the contractile properties of restenosis. Other
      factors such as macrophage-induced inflammation and reactive oxygen species
      accumulation may also contribute to restenosis. This is the second reported case
      of restenosis following angioplasty to treat vasospasm, although restenosis is a
      known complication of angioplasty for treatment of atherosclerosis. In addition,
      this is the first case of restenosis in the bilateral ICAs following angioplasty
      for vasospasm. This report presents an illustrative case study and reviews the
      pathophysiology of angioplasty and restenosis.

PMID- 19409004
TI  - Intracranial aneurysms presenting with mass effect over the anterior optic
      pathways: neurosurgical management and outcomes.
AB  - OBJECT: Intracranial aneurysms may grow closer to anterior optic pathways,
      causing mass effect over these anatomical structures, including visual deficit.
      The authors retrospectively reviewed a series of aneurysms in patients presenting
      with visual field deficit caused by mass effect, to analyze the aneurysm's
      characteristics, the neurosurgical management of these aneurysms, as well as
      their clinical, visual, and radiological outcomes. METHODS: The authors reviewed
      the medical charts, neuroimaging examination results, and surgical videos of 15
      patients presenting with visual symptoms caused by an aneurysm's mass effect over
      the anterior optic pathways. These patients were treated at the Department of
      Neurosurgery, Center of Neurology and Neurosurgery Associates, Hospital
      Beneficencia Portuguesa de Sao Paulo, Brazil. Statistical analysis was performed
      to identify the variables related to partial or total recovery of the visual
      symptoms. RESULTS: All patients underwent microsurgical clip placement and
      emptying of their aneurysms. After a mean follow-up of 38.5 months, the mean
      postoperative Glasgow Outcome Scale score was 4.33, and the visual outcomes were
      as follows: 1 patient (6.6%) unchanged, 7 (46.6%) improved, and 7 (46.6%)
      experienced complete recovery from visual deficits. The variables that influenced
      the visual outcomes were the size of the aneurysm (p = 0.039), duration of the
      visual symptoms (p = 0.002), aneurysm wall calcification (p = 0.010), and
      intraluminal thrombosis (p = 0.007). Postoperative examination using digital
      subtraction angiography showed complete aneurysm occlusion in 14 (93.3%) of the
      15 patients. CONCLUSIONS: Intracranial aneurysms causing mass effect over the
      anterior optic pathways usually present with complex features. The best treatment
      option must include not only the aneurysm occlusion but also relief of the mass
      effect. Microsurgical clip placement with reduction of aneurysmal mass effect
      achieved improvement in visual ability or recovery from visual impairment, as
      well as total aneurysm occlusion, in 93.3% of the study group. Therefore, this
      option is well supported as the first choice of treatment for intracranial
      aneurysms presenting with mass effect over the anterior visual pathways.

PMID- 19409005
TI  - Cavernous carotid aneurysms: to treat or not to treat?
AB  - Most cavernous carotid aneurysms (CCAs) are considered benign lesions, most often
      asymptomatic, and to have a natural history with a low risk of life-threatening
      complications. However, several conditions may exist in which treatment of these
      aneurysms should be considered. Several options are currently available regarding
      the management of CCAs with resultant good outcomes, namely expectant management,
      luminal preservation strategies with or without addressing the aneurysm directly,
      and Hunterian strategies with or without revascularization procedures. In this
      article, we discuss the sometimes difficult decision regarding whether to treat
      CCAs. We consider the natural history of several types of CCAs, the clinical
      presentation, the current modalities of CCA management and their outcomes to aid
      in the management of this heterogeneous group of cerebral aneurysms.

PMID- 19409006
TI  - Giant serpentine aneurysms.
AB  - Segal and McLaurin first described giant serpentine aneurysms, based on their
      distinct angiographic features, in 1977. These lesions are >or= 25 mm, partially
      thrombosed aneurysms with a patent, serpiginous vascular channel that courses
      through the aneurysm. There is a separate inflow and outflow of the aneurysm, of
      which the outflow channel supplies brain parenchyma in the territory of the
      parent vessel. Given the large size, unique neck, and dependent distal vessels,
      these aneurysms pose a technical challenge in treatment. Initial management has
      included surgical obliteration, but as endovascular techniques have evolved,
      treatment options too have expanded. In this review the authors attempt to
      summarize the existing body of literature on this rare entity and describe some
      of their institutional management strategies.

PMID- 19409007
TI  - Management of anterior inferior cerebellar artery aneurysms: an illustrative case
      and review of literature.
AB  - Aneurysms of the anterior inferior cerebellar artery (AICA) are relatively rare
      among intracranial aneurysms. They can occur in 1 of 3 regions of the AICA: 1)
      craniocaudal (high or low riding), 2) mediolateral-premeatal (proximal), and 3)
      meatal-postmeatal (distal). The management strategies for treatment differ
      according to the location and configuration of the aneurysm. The existing body of
      neurosurgical literature contains articles published on aneurysms arising from
      the AICA near the basilar artery (BA), intracanalicular/meatal aneurysms, and
      distal AICA. Several therapeutic options exist, encompassing microsurgical and
      endovascular techniques. The authors describe a case of treatment involving a
      large BA-AICA aneurysm approached via exposure of the presigmoid dura using a
      retromastoid suboccipital craniectomy and partial petrosectomy. Treatment of
      these lesions requires detailed knowledge of the anatomy, and an anatomical
      overview of the AICA with its arterial loops and significant branches is
      presented, including a discussion of the internal auditory (labyrinthine) artery,
      recurrent perforating arteries, subarcuate artery, and cerebellosubarcuate
      artery. The authors discuss the various surgical approaches (retromastoid, far
      lateral, subtemporal, and transclival) with appropriate illustrations, citing the
      advantages and disadvantages in accessing these AICA lesions in relation to these
      approaches. The complications of these different surgical techniques and possible
      clinical effects of parent artery occlusion during AICA surgery are highlighted.

PMID- 19409009
TI  - Endovascular occlusion of a ruptured transitional aneurysm associated with a
      developmental venous anomaly. Case report.
AB  - Developmental venous anomalies (DVAs) represent a rare cause of intraparenchymal
      hemorrhage. This case demonstrates an unusual DVA associated with venous
      hypertension, arteriovenous shunting, and a ruptured transitional aneurysm. The
      authors describe the first use of embolization as a treatment method for an
      unstable ruptured transitional aneurysm associated with a DVA. This 33-year-old
      man suffered acute onset of headache, gait ataxia, and left hemiparesis. Computed
      tomography brain scans demonstrated a deep paramedian right frontal
      intraparenchymal hemorrhage. No cavernous malformation was apparent on MR
      imaging. Diagnostic angiography revealed arteriovenous shunting from the right
      anterior and middle cerebral arteries to a large DVA with an associated
      arteriovenous fistula, with a 3-mm aneurysm in the transition from pericallosal
      artery to the collecting vein. Both surgical and endovascular treatment options
      were considered. The patient underwent repeat angiography on hospital Day 7, at
      which time the aneurysm had increased to 5 mm, and endovascular treatment was
      selected. Acrylic occlusion of the aneurysm was performed and confirmed
      angiographically. The patient's neurological symptoms resolved throughout the
      hospital stay, and he remains symptom free in the 10 months since treatment.
      Developmental venous anomalies are not usually associated with arteriovenous
      shunting and aneurysms as a source of intraparenchymal hemorrhage. Endovascular
      occlusion of the aneurysm without blockage of physiologically necessary venous
      structures is a possible method of treatment for this complex mixed vascular
      lesion, and has proven safe and effective in this patient. To the authors'
      knowledge, this is the first presentation of this situation in the literature.

PMID- 19409008
TI  - Fenestrated aneurysm clips in the surgical management of anterior communicating
      artery aneurysms: operative techniques and strategy. Clinical article.
AB  - OBJECT: Aneurysms of the anterior communicating artery (ACoA) can be a
      considerable challenge to treat surgically based on variations in the anatomy and
      morphological features of the ACoA complex. The fenestrated aneurysm clip can be
      a simple and practical tool in the operative management of ACoA aneurysms. The
      goal in this study was to characterize the particular surgical situations in
      which the use of a fenestrated clip facilitates the clip ligation of ACoA
      aneurysms. METHODS: The authors present their operative strategy and techniques
      for the use of fenestrated clips in the treatment of ACoA aneurysms. RESULTS: One
      hundred ninety-nine patients underwent surgical clipping of an ACoA aneurysm at
      the authors' institution between the years 1991 and 2008. Of these patients,
      fenestrated aneurysm clips were used in 20 cases (10%). The following structures
      were enclosed in the clip aperture: ipsilateral A(2) artery, 12 patients (60%);
      ipsilateral A(1) artery, 4 patients (20%); ipsilateral A(1) artery plus recurrent
      artery of Heubner, 1 patient (5%); ACoA, 1 patient (5%); frontopolar artery, 1
      patient (5%); and no structures, 1 patient (5%). Aneurysms approached from the
      left side more frequently required fenestrated clips than did right-sided
      aneurysms (80 vs 20%, p = 0.0073). In all cases, patency of the A(2) vessels was
      confirmed on postoperative angiography. In 2 patients, small remnant aneurysm
      necks were identified on postoperative angiography. CONCLUSIONS: The use of
      fenestrated aneurysm clips can minimize tedious and potentially dangerous
      dissection of adherent branch vessels, while maintaining the integrity of
      structures placed within the clip aperture. The ACoA aneurysms pointing in a
      superior direction are more likely to require clip fenestration around the A(2)
      vessel, whereas those pointing in an inferior direction are more likely to
      require clip fenestration around the A(1) vessel. The parallel approximation of
      the fenestrated clip blades makes them especially useful in the treatment of
      large or giant aneurysms.

PMID- 19409010
TI  - Pathogenesis and radiobiology of brain arteriovenous malformations: implications
      for risk stratification in natural history and posttreatment course.
AB  - Brain arteriovenous malformations (BAVMs) are an important cause of intracerebral
      hemorrhage (ICH) in young adults. Biological predictors of future ICH risk are
      lacking, and controversy exists over previous studies of natural history risk
      among predominantly ruptured BAVM cohorts. Recent studies have suggested that the
      majority of BAVMs are now diagnosed as unruptured lesions, and that the risk
      according to natural history among these lesions may be less than previously
      assumed. In the first part of this review, the authors discuss available data on
      the natural history of BAVMs and highlight the need for future studies that aim
      to develop surrogate biomarkers of disease progression that accurately predict
      future risk of ICH in BAVMs. The etiology of BAVM remains unknown. Recent studies
      have suggested a role for genetic factors in the pathogenesis of sporadic BAVM,
      which is further supported by reports of familial occurrence of BAVM and
      association with known systemic genetic disorders (such as Osler-Weber-Rendu
      disease, Sturge-Weber disease, and Wyburn-Mason syndrome). Molecular
      characterization of BAVM tissue demonstrates a highly angiogenic milieu with
      evidence of increased endothelial cell turnover. Taken together with a number of
      reports of de novo BAVM formation, radiographic growth after initial BAVM
      diagnosis, and regrowth after successful treatment of BAVM, these findings
      challenge the long-held assumption that BAVMs are static lesions of congenital
      origin. In the second part of this review, the authors discuss available data on
      the origins of BAVM and offer insights into future investigations into genetics
      and endothelial progenitor cell involvement in the pathogenesis of BAVM. Current
      treatment options for BAVM focus on removal or obliteration of the lesion in an
      attempt to protect against future ICH risk, including microsurgical resection,
      endovascular embolization, and stereotactic radiosurgery (SRS). In the third part
      of this review, the authors discuss available data on SRS in BAVMs and highlight
      the need for future studies on the radiobiology of BAVMs, especially in regard to
      biomarker detection for tracking SRS response during the latency period. Insights
      from future investigations in BAVM may not only prove important for the
      development of novel therapies and relevant biomarkers for BAVM, but could also
      potentially benefit a variety of other disorders involving new vessel formation
      in the CNS, including stroke, tumors, moyamoya disease, and other cerebrovascular
      malformations.

PMID- 19409011
TI  - Medial pectoral nerve transfer.

PMID- 19409013
TI  - Resonant and notch behavior in intracranial pressure dynamics.
AB  - OBJECT: The intracranial pulse pressure is often increased when neuropathology is
      present, particularly in cases of increased intracranial pressure (ICP) such as
      occurs in hydrocephalus. This pulse pressure is assumed to originate from
      arterial blood pressure oscillations entering the cranium; the fact that there is
      a coupling between the arterial blood pressure and the ICP is undisputed. In this
      study, the nature of this coupling and how it changes under conditions of
      increased ICP are investigated. METHODS: In 12 normal dogs, intracarotid and
      parenchymal pulse pressure were measured and their coupling was characterized
      using amplitude and phase transfer function analysis. Mean intracranial ICP was
      manipulated via infusions of isotonic saline into the spinal subarachnoid space,
      and changes in transfer function were monitored. RESULTS: Under normal
      conditions, the ICP wave led the arterial wave, and there was a minimum in the
      pulse pressure amplitude near the frequency of the heart rate. Under conditions
      of decreased intracranial compliance, the ICP wave began to lag behind the
      arterial wave and increased significantly in amplitude. Most interestingly, in
      many animals the pulse pressure exhibited a minimum in amplitude at a mean
      pressure that coincided with the transition from a leading to lagging ICP wave.
      CONCLUSIONS: This transfer function behavior is characteristic of a resonant
      notch system. This may represent a component of the intracranial Windkessel
      mechanism, which protects the microvasculature from arterial pulsatility. The
      impairment of this resonant notch system may play a role in the altered pulse
      pressure in conditions such as hydrocephalus and traumatic brain swelling. New
      models of intracranial dynamics are needed for understanding the frequency
      sensitive behavior elucidated in these studies and could open a path for
      development of new therapies that are geared toward addressing the pulsation
      dysfunction in pathological conditions, such as hydrocephalus and traumatic brain
      injury, affecting ICP and flow dynamics.

PMID- 19409012
TI  - Medial pectoral nerve to musculocutaneous nerve neurotization for the treatment
      of persistent birth-related brachial plexus palsy: an 11-year institutional
      experience.
AB  - OBJECT: Medial pectoral nerve (MPN) to musculocutaneous nerve (MCN) neurotization
      for recovery of elbow flexion by biceps reinnervation is a valid option following
      traumatic injury to the upper brachial plexus. A major criticism of the
      application of this technique in infants is the smaller size of the MPN and
      mismatch of viable axons. We describe our institutional experience utilizing this
      procedure and critically examine functional outcomes. METHODS: Office charts and
      hospital records of children from over an 11-year period beginning January 1997
      were reviewed. Of the 53 children of various ages undergoing brachial plexus
      exploration for traumatic injury of any nature, 20 underwent MPN to MCN
      neurotization as a part of an overall procedure in the first year of life to
      treat birth-related brachial plexus palsy and had at least 9 months' follow-up.
      Medial pectoral nerve to MCN neurotization was chosen if the results of clinical
      examination and intraoperative electrophysiological evidence were consistent with
      medial cord function. Functional recovery was defined as the ability of the child
      to bring their hand to their mouth. RESULTS: Sixteen patients (80%) gained
      functional recovery. The median age at surgery was 7 months. Median time to first
      clinic visit documenting recovery was 11.5 months and median overall follow up
      was 21.5 months. Preoperative hand function was a useful predictor of recovery of
      elbow flexion. CONCLUSIONS: Medial pectoral nerve to MCN neurotization is a valid
      surgical option for the reinnervation of the biceps muscle for birth-related
      brachial plexus palsy when the hand is functional preoperatively. Useful elbow
      flexion can be expected in the majority of these children.

PMID- 19409014
TI  - Correlation between ventriculomegaly on prenatal magnetic resonance imaging and
      the need for postnatal ventricular shunt placement.
AB  - OBJECT: Pediatric neurosurgeons are increasingly called on to provide prognostic
      data regarding the antenatal diagnosis of ventriculomegaly. This study was
      designed to determine if there is a correlation between prenatal MR imaging
      results and the need for ventricular shunt placement during the neonatal period.
      METHODS: The authors retrospectively reviewed the prenatal MR imaging data of 38
      consecutive patients who had been referred for neurosurgical consultation
      following the diagnosis of ventriculomegaly. The outcome measure was placement of
      a ventricular shunt. Assessed parameters included prenatal atrial diameter (AD),
      gestational age at MR imaging, time between imaging studies, presence of
      concomitant CNS anomalies, laterality of ventriculomegaly, fetal sex, and
      temporal evolution of ventriculomegaly. Logistic regression analysis was
      completed with the calculation of appropriate ORs and 95% CIs. RESULTS: Six
      patients (16%) required shunt placement, all with an AD > or = 20 mm (mean 23.8
      mm) at the time of imaging. Eight patients had presented with an AD > or = 20 mm.
      Atrial diameter was the only presenting feature that correlated with shunt
      placement (OR 1.58, 95% CI 1.10-2.25, p = 0.01). Logistic regression analysis
      revealed no statistical correlation between the need for ventricular shunting and
      gestational age at MR imaging, time between imaging studies, fetal sex, presence
      of additional CNS anomalies, and laterality of the ventriculomegaly. CONCLUSIONS:
      When assessed using MR imaging, an AD > or = 20 mm at any gestational age is
      highly associated with the need for postnatal shunting. Patients with concomitant
      CNS anomalies did not require shunts at a greater rate than those with isolated
      ventriculomegaly. Further studies are required to assess the long-term outcome of
      this patient population.

PMID- 19409015
TI  - Surgical outcome of tuberculous meningitis hydrocephalus treated by endoscopic
      third ventriculostomy: prognostic factors and postoperative neuroimaging for
      functional assessment of ventriculostomy.
AB  - OBJECT: Endoscopic third ventriculostomy (ETV) is increasingly being used as an
      alternative treatment for post-tuberculous meningitis (TBM) hydrocephalus. The
      aim of this study was to affirm the role of ETV in patients with TBM
      hydrocephalus and also to study the usefulness of cine phase-contrast MR imaging
      (cine MR imaging) for functional assessment of the ETV stoma. An additional goal
      was to identify factors that influence the outcome of ETV, so as to define
      patients with TBM hydrocephalus in whom ETV is warranted. METHODS: Twenty-six
      patients with TBM hydrocephalus treated with ETV were evaluated clinically and
      with cine MR imaging postoperatively. The duration of follow-up ranged from 1 to
      15 months. The authors evaluated flow void changes in the floor of the third
      ventricle and analyzed parameters from the preoperative data, which they then
      used as a basis for comparison between endoscopically successful and
      endoscopically unsuccessful cases. RESULTS: The overall success rate of ETV in
      TBM hydrocephalus was 73.1% in this case series. Cine MR imaging showed a
      sensitivity of 94.73% and specificity of 71.42% for the functional assessment of
      third ventriculostomy in these patients, with the efficacy being maintained
      during follow-up. The outcome of ETV showed a statistically significant
      correlation with the stage of illness and presence of intraoperative cisternal
      exudates. Although duration of symptoms and duration of preoperative
      antituberculous therapy (ATT) appeared to influence the outcome, their
      correlation with outcome was not statistically significant. CONCLUSIONS:
      Endoscopic third ventriculostomy should be considered as the first surgical
      option for CSF diversion (that is, before shunt surgery) in patients with TBM
      hydrocephalus. Cine MR imaging is a highly effective noninvasive tool for the
      postoperative functional assessment of stomata. Patients who presented with a
      history of longer duration and those who were administered preoperative ATT for a
      longer period had a better outcome of endoscopic treatment. Outcome was poorer in
      patients who presented with higher stages of illness and in those in whom
      cisternal exudates were observed intraoperatively.

PMID- 19409016
TI  - Predicting postresection hydrocephalus in pediatric patients with posterior fossa
      tumors.
AB  - OBJECT: Approximately 30% of children with posterior fossa tumors exhibit
      hydrocephalus after tumor resection. Recent literature has suggested that
      prophylactic endoscopic third ventriculostomy diminishes the risk of this event.
      Because the majority of patients will not have postoperative hydrocephalus, a
      preoperative clinical prediction rule that identifies patients at high or low
      risk for postresection hydrocephalus would be helpful to optimize the care of
      these children. METHODS: The authors evaluated a derivation cohort of 343
      consecutive children with posterior fossa tumors who underwent treatment between
      1989 and 2003. Multivariate methods were used on these data to generate the
      Canadian Preoperative Prediction Rule for Hydrocephalus. The rule's estimated
      risk of postresection hydrocephalus was compared with risk observed in 111
      independent patients in the validation cohort. RESULTS: Variables identified as
      significant in predicting postresection hydrocephalus were age < 2 years (score
      of 3), papilledema (score of 1), moderate to severe hydrocephalus (score of 2),
      cerebral metastases (score of 3), and specific estimated tumor pathologies (score
      of 1). Patients with scores > or = 5 were deemed as high risk. Predicted
      probabilities for the high- and low-risk groups were 0.73 and 0.25, respectively,
      from the derivation cohort, and 0.59 and 0.14 after prevalence adjustment
      compared with the observed values of 0.42 and 0.17 in the validation cohort.
      CONCLUSIONS: A patient's score on the Preoperative Prediction Rule for
      Hydrocephalus will allow improved patient counseling and surgical planning by
      identifying patients at high risk of developing postresection hydrocephalus.
      These patients might selectively be exposed to the risks of preresection CSF
      diversion to improve outcome.

PMID- 19409017
TI  - Intratentorial osteochondrolipoma in a 9-year-old boy.
AB  - Intracranial osteolipomas and chondromas are rare benign tumors. Forty-five
      chondromas, mostly supratentorial, have been reported in the literature since
      1981, with origins most commonly in the sellar regions. Twenty-one osteolipomas
      have been described to date, usually located near the tuber cinereum or the
      corpus callosum. The authors present a case of an osteochondrolipoma arising from
      the tentorium diagnosed in a pediatric patient at the age of 9 years. The case
      and treatment are discussed, and a review of the literature is provided.

PMID- 19409018
TI  - Intracranial growing teratoma syndrome mimicking tumor relapse: a diagnostic
      dilemma.
AB  - OBJECT: It is important to differentiate growing teratoma syndrome (GTS) from
      tumor recurrence in the setting of an enlarging residual mass present after
      treatment of intracranial germ cell tumors (GCTs). The aim of this study was to
      determine the incidence of intracranial GTS and present its clinical
      manifestations in detail. METHODS: The authors performed a retrospective cohort
      study of 52 consecutive patients with newly diagnosed intracranial GCTs who
      presented between January 2000 and December 2006. The records were screened to
      identify a study cohort in which all patients had regrowing tumor mass despite
      normalization of tumor markers during or after treatment of GCTs. RESULTS: In 6
      (11.5%) of 52 patients the pathological diagnosis was GTS. The median patient age
      at diagnosis was 14.5 years (range 2 months-17 years), and the primary tumors
      included 4 mixed GCTs and 2 immature teratomas. After second-look surgery,
      histological testing revealed the lesions to be mature teratoma in all patients.
      Three of 6 patients subsequently underwent radiation therapy and 1 patient
      received additional chemotherapy for spinal seeding. CONCLUSIONS: In enlarging
      residual masses after treatment of intracranial GCTs, GTS should be kept in mind
      in the differential diagnosis of tumor recurrence especially if there is a
      radiographic mismatch with serum marker test results. If technically feasible,
      second-look surgery may be necessary for an accurate diagnosis.

PMID- 19409019
TI  - Successful surgical treatment of craniopharyngioma in very young children.
AB  - OBJECT: Given the potential morbidity of cranial irradiation in young children,
      the risk-benefit analysis of limited surgery plus irradiation versus radical
      resection may favor the latter strategy. The purpose of this study was to assess
      the oncological, endocrinological, and functional outcomes of patients 5 years of
      age and younger who underwent radical resection of craniopharyngiomas. METHODS:
      Between 1991 and 2008, 19 children age < or = 5 years were diagnosed with a
      craniopharyngioma and underwent radical resection by the senior author (J.H.W.).
      Data were retrospectively collected on these 19 patients (11 males, 8 females;
      mean age 3.2 years) to assess the efficacy and impact of surgical treatment.
      RESULTS: Eighteen (95%) of 19 patients underwent gross-total resection (GTR)
      confirmed by intraoperative inspection and postoperative imaging. There was no
      operative death and 18 of (95%) 19 patients were alive at a mean follow-up of 9.4
      years (median 8.3 years). Six patients (31%) had a total of 7 tumor recurrences
      treated by repeat GTR in 5 patients and Gamma knife surgery in 1 patient. No
      patient required conventional, fractionated radiation therapy. Disease control
      was achieved surgically in 17 (89.5%) patients and with surgery and Gamma knife
      surgery in 1 patient, yielding an overall rate of disease control of 95% without
      the use of conventional radiotherapy. New-onset diabetes insipidus occurred in
      50% of patients. Vision worsened in 1 patient, and there was no long-term
      neurological morbidity. CONCLUSIONS: In this retrospective series, children aged
      < or = 5 years with craniopharyngiomas can have excellent outcomes with minimal
      morbidity after radical resection by an experienced surgeon. Disease control in
      this population can be successfully achieved with GTR alone in the majority of
      cases, avoiding the detrimental effects of radiotherapy in this vulnerable
      population.

PMID- 19409020
TI  - Spinal congenital dermal sinus with dual ostia.
AB  - OBJECT: Congenital dermal sinus (CDS) usually develops in the midline of the body
      as a single tract. To date, only a few patients with multiple CDS tracts and
      ostia have been reported. The authors analyzed the clinical features of patients
      with spinal CDS and multiple ostia and proposed a novel hypothesis for the
      pathogenesis of the atypical CDS. METHODS: Five patients with spinal CDS and
      multiple ostia were included. The clinical, radiological, and operative features
      of these patients were reviewed retrospectively. RESULTS: Three patients
      demonstrated bilateral paramedian ostia at the same or a very similar spinal
      level. One patient showed a paramedian and a midline ostium. One patient had 2
      unilateral paramedian ostia at different spinal levels. The layers of the
      internal ending of CDS tracts were diverse. Complete removal of the tracts was
      possible in all patients. Two patients had dermoid tumors. All patients had an
      associated anomaly, such as a lumbosacral lipoma or the Currarino triad. The
      authors propose a "zipping error" hypothesis for the formation of dual ostia
      located at the spinal level of primary neurulation. An associated anomaly such as
      a lumbosacral lipoma may contribute to the formation of dual ostia. CONCLUSIONS:
      Unilateral or bilateral dual ostia may be present in patients with CDS,
      especially when an associated anomaly is present. The atypical CDS may develop
      from aberrant neural tube closure.

PMID- 19409021
TI  - Embryopathogenetic surgicoanatomical classification of dysraphism and surgical
      outcome of spinal lipoma: a nationwide multicenter cooperative study in Japan.
AB  - OBJECT: The natural history of asymptomatic spinal lipoma in infancy remains
      unclear, and the indication for the prophylactic untethering operation is still
      debatable. To address this question, a multicenter cooperative study for the
      treatment of spinal lipoma was performed by the 7 most active institutions in
      neurosurgical care for spina bifida in Japan between 2001 and 2005. METHODS:
      Patients were classified using the embryopathogenetic surgicoanatomical
      classification. Their neurosurgical postoperative course was analyzed using the
      Spina Bifida Neurological Scale. Among 261 patients, 159 were asymptomatic and
      102 were symptomatic. RESULTS: Of the 136 patients for whom prophylactic
      surgeries were performed, 135 remained asymptomatic and only 1 (0.4%) of the 261
      patients presented with mild sensory disturbance. Mild foot deformity was
      identified in 1 (4.3%) of 23 conservatively observed patients. Of 100 symptomatic
      patients, deterioration after surgery was seen in 6%, and improvement in 44%.
      Complete resolution of symptoms was seen in only 14.2%. Filar types for patients
      > 3 years old improved in Spina Bifida Neurological Scale scores from 12.3 to
      14.0. The mean age of symptomatic patients with lipomyelomeningocele was the
      youngest of all (1.3 years), which indicates lipomyelomeningocele may deteriorate
      in early infancy. Improvements from surgery were seen for all types of lipoma
      except the caudal type, presenting at an older mean age (15 years). CONCLUSIONS:
      A low rate of postsurgical worsening indicates that surgeries for asymptomatic
      and symptomatic lipomas are safe. Surgeries done after the onset of symptoms
      seldom cure the patients. These two results support early untethering for any
      kind of lipoma; however, further study of the natural history is required.

PMID- 19409022
TI  - Ultrasound-aided fixation of a biodegradable cranial fixation system: uses in
      pediatric neurosurgery.
AB  - OBJECT: Bioresorbable implant systems have been used in neurosurgery for the
      rigid fixation of cranial and facial bones. A relatively recent advancement has
      been the fixation of these implants using an ultrasonic device. The experience
      with such a device in neurosurgical practice has been limited. The authors report
      on their experience with ultrasound-aided fixation of bioresorbable implants in
      pediatric neurosurgical practice. METHODS: The study consisted of 2 parts. The
      retrospective portion consisted of a chart review of pertinent clinical
      information, complications, and outcomes after the use of a commercially
      available ultrasound-aided bioresorbable implant system (SonicWeld Rx, KLS Martin
      L.P.). Follow-up was obtained in all patients via clinical examination or
      telephone interview. The prospective portion of the study consisted of video
      analysis of the implantation technique in a routine craniotomy. Implantation
      times were measured, and delays during treatment were noted. RESULTS: Over a
      period of 2 years, 28 consecutive patients underwent placement of these implants
      for bone fixation during craniotomies or craniofacial reconstructions. The only
      complication was seen in a child with Crouzon syndrome, who had a wound infection
      caused by Serratia sepsis from a central venous line infection. There were no
      repeated operations for implant-related swelling, and no cases of premature plate
      resorption, bone instability, or settling. In vivo, the average time required to
      implant a resorbable pin with this system was 22 seconds. CONCLUSIONS: The use of
      a bioresorbable implant system with ultrasound-aided pin fixation in pediatric
      neurosurgery cases achieved adequate stability with few complications. This
      system was easy to use and provided rapid fixation of implants.

PMID- 19409023
TI  - Paraspinal arteriovenous malformations in children.
AB  - Arteriovenous malformations (AVMs) within the spinal canal and in the paraspinal
      region are unusual. Spinal cord and dural AVMs or arteriovenous fistulas have
      been the subject of numerous reports, but paraspinal malformations causing venous
      congestion or hemorrhage in the spinal canal are rare and present special
      diagnosis and management challenges. The authors review previously published
      reports on 16 children with paraspinal AVMs. They also describe the 17th case of
      a child with a paraspinal AVM who presented with a spontaneous spinal epidural
      hematoma. To the best of the authors' knowledge, there has been no other case of
      a spinal epidural hematoma associated with a paraspinal AVM. In each of the 17
      cases, the vascular lesion was successfully obliterated using endovascular
      therapy. Embolization with permanent occlusive agents is an effective treatment
      for these rare but potentially debilitating lesions.

PMID- 19409024
TI  - A rare case of hemangioma of infancy presenting as intraspinal hemorrhage.
AB  - Hemangiomas of infancy (HOIs) are among the most common benign tumors of
      childhood and classically appear as a vascular stain or small vascular papule at
      birth. They are unique tumors due to their propensity to proliferate, involute,
      and finally regress. These lesions can be associated with visceral malformations
      that have been shown to affect mainly the liver and the gastrointestinal tract,
      but rarely the spinal cord. The authors report a rare case of a spinal HOI in a 2
      month-old infant presenting with quadriplegia due to intratumoral hemorrhage.
      Following resection of the lesion, the child regained function. This first
      reported case of spinal HOI suggests another location for hemangiomatosis. Spinal
      HOI should be included in the differential diagnosis of acute intraspinal
      hemorrhage in infants.

PMID- 19409025
TI  - Acute subdural hematoma secondary to distal middle cerebral artery aneurysm
      rupture in a newborn infant.
AB  - The authors present the case of a peripheral aneurysmal lesion that developed in
      a newborn baby and was successfully treated by endovascular parent artery
      occlusion. Given the natural history of aneurysms, which are prone to rupture and
      to cause deleterious intracerebral hemorrhage, with high mortality rates,
      aggressive and early management (endovascular or surgical) is recommended.

PMID- 19409026
TI  - Keyhole to the brain: Walter Dandy and neuroendoscopy.
AB  - In the early 1920s, Walter E. Dandy began translating the field of endoscopy to
      neurosurgery. In the ensuing years, Dandy, who would become known as the "Father
      of Neuroendoscopy," applied his own ingenuity in combination with guidance from
      prominent medical contemporaries in the development of the early neuroendoscope.
      This paper reviews his contributions to the early evolution of this growing and
      important field of neurosurgery.

PMID- 19409027
TI  - Bringing forth the old: addition of legacy content to the Journal of Neurosurgery
      Publishing Group website.

PMID- 19409028
TI  - Impact of the Accreditation Council for Graduate Medical Education work-hour
      regulations on neurosurgical resident education and productivity.
AB  - OBJECT: Recently, the Institute of Medicine examined resident duty hours and
      their impact on patient safety. Experts have suggested that reducing resident
      work hours to 56 hours per week would further decrease medical errors. Although
      some reports have indicated that cutbacks in resident duty hours reduce errors
      and make resident life safer, few authors have specifically analyzed the effect
      of the Accreditation Council for Graduate Medical Education (ACGME) duty-hour
      limits on neurosurgical resident education and the perceived quality of training.
      The authors have evaluated multiple objective surrogate markers of resident
      performance and quality of training to determine the impact of the 80-hour
      workweek. METHODS: The United States Medical Licensing Examination (USMLE) Step 1
      data on neurosurgical applicants entering ACGME-accredited programs between 1998
      and 2007 (before and after the implementation of the work-hour rules) were
      obtained from the Society of Neurological Surgeons. The American Board of
      Neurological Surgery (ABNS) written examination scores for this group of
      residents were also acquired. Resident registration for and presentations at the
      American Association of Neurological Surgeons (AANS) annual meetings between 2002
      and 2007 were examined as a measure of resident academic productivity. As a case
      example, the authors analyzed the distribution of resident training hours in the
      University of Virginia (UVA) neurosurgical training program before and after the
      institution of the 80-hour workweek. Finally, program directors and chief
      residents in ACGME-accredited programs were surveyed regarding the effects of the
      80-hour workweek on patient care, resident training, surgical experience, patient
      safety, and patient access to quality care. Respondents were also queried about
      their perceptions of a 56-hour workweek. RESULTS: Despite stable mean USMLE Step
      1 scores for matched applicants to neurosurgery programs between 2000 and 2008,
      ABNS written examination scores for residents taking the exam for self-assessment
      decreased from 310 in 2002 to 259 in 2006 (16% decrease, p < 0.05). The mean
      scores for applicants completing the written examination for credit also did not
      change significantly during this period. Although there was an increase in the
      number of resident registrations to the AANS meetings, the number of abstracts
      presented by residents decreased from 345 in 2002 to 318 in 2007 (7% decrease, p
      < 0.05). An analysis of the UVA experience suggested that the 80-hour workweek
      leads to a notable increase in on-call duty hours with a profound decrease in the
      number of hours spent in conference and the operating room. Survey responses were
      obtained from 110 program directors (78% response rate) and 122 chief residents
      (76% response rate). Most chief residents and program directors believed the 80
      hour workweek compromised resident training (96%) and decreased resident surgical
      experience (98%). Respondents also believed that the 80-hour workweek threatened
      patient safety (96% of program directors and 78% of chief residents) and access
      to quality care (82% of program directors and 87% of chief residents). When asked
      about the effects of a 56-hour workweek, all program directors and 98% of the
      chief residents indicated that resident training and surgical education would be
      further compromised. Most respondents (95% of program directors and 84% of chief
      residents) also believed that additional work-hour restrictions would jeopardize
      patient care. CONCLUSIONS: Neurological surgery continues to attract top-quality
      resident applicants. Test scores and levels of participation in national
      conferences, however, indicate that the 80-hour workweek may adversely affect
      resident training. Subjectively, neurosurgical program directors and chief
      residents believe that the 80-hour workweek makes neurosurgical training and the
      care of patients more difficult. Based on experience with the 80-hour workweek,
      educators think that a 56-hour workweek would further compromise neurosurgical
      training and patient care in the US.

PMID- 19409029
TI  - Resident duty hour regulation and patient safety: establishing a balance between
      concerns about resident fatigue and adequate training in neurosurgery.
AB  - Postgraduate training in medicine has been under scrutiny over the past 10 years
      with a major focus on physician personal health and patient safety. The
      culmination of a series of events led to the 80-hour work week instituted by the
      Accreditation Council on Graduate Medical Education in 2003. The effect this
      mandate has had on surgical education, and specifically training in neurological
      surgery, has been incompletely evaluated. Nevertheless, external pressure has
      prompted the Institute of Medicine to issue a new report on resident work hours
      and patient safety. In this report, the authors focus on the unique aspects of
      neurosurgical training in which physicians are trained to safely and effectively
      carry out complex high-risk tasks, the experience from abroad where work hours
      are reduced to well below 80 hours/week, and the risk that further reduction in
      work hours poses to the public. The authors conclude that there must be an
      adequate balance between the risks associated with resident fatigue and those
      associated with an inexperienced neurosurgical work force for public health.

PMID- 19409030
TI  - A review of valproate in psychiatric practice.
AB  - Valproate (2-propylpentanoate) is available as valproic acid, sodium valproate
      and semisodium valproate. It has actions on dopamine, GABA and glutamate
      neurotransmission and intracellular signaling. Its main psychiatric use is to
      treat bipolar disorder. It has been used in other psychiatric disorders,
      including schizophrenia and borderline personality disorder, but data are
      insufficient to recommend this. In acute mania, valproate monotherapy has similar
      efficacy to antipsychotic drugs and lithium whereas the combination of valproate
      and an antipsychotic is more effective than either drug alone. In maintenance
      treatment of bipolar disorder, valproate monotherapy has comparable efficacy to
      olanzapine although placebo-controlled evidence is limited. Maintenance treatment
      with valproate and quetiapine or olanzapine is more efficacious than valproate
      alone when an acute episode responds to the combination. Common adverse effects
      of valproate include weight gain, gastrointestinal symptoms, sedation, tremor and
      mild elevation of hepatic enzymes. Serious hepatic toxicity is rare in adults.
      Many adverse effects are dose related and resolve with dose reduction. Valproate
      is teratogenic and specifically associated with neural tube defect. Preliminary
      evidence has linked in utero exposure to decreased verbal intelligence in the
      offspring. These effects, plus a probable increased risk of polycystic ovary
      syndrome, limit valproate's use in women of childbearing potential.

PMID- 19409032
TI  - Epigenomic targets for the treatment of respiratory disease.
AB  - BACKGROUND: A number of processes lead to epigenetic and epigenomic
      modifications. OBJECTIVE: To address the importance of epigenomics in respiratory
      disease. METHODS: Studies of epigenomics were analysed in relation to chronic
      respiratory diseases. RESULTS/CONCLUSION: In lung cancer and mesothelioma, a
      number of genes involved in carcinogenesis have been demonstrated to be
      hypermethylated, implicating epigenomic changes in the aetiology of these
      cancers. Hypermethylated genes have also been associated with lung cancer
      recurrence, indicating epigenomic regulation of metastasis. In airway diseases,
      modulation of histone function may activate inflammatory mechanisms in chronic
      obstructive pulmonary disease patients and lead to relative steroid resistance.
      There is emerging evidence for the role of epigenetic changes in chronic lung
      diseases such as asthma, including responses to environmental exposures in utero
      and to the effects of air pollution. Insight into epigenomics will lead to the
      development of novel biomarkers and treatment targets in respiratory diseases.

PMID- 19409033
TI  - Glioblastoma multiforme: a review of therapeutic targets.
AB  - Glioblastoma is the commonest primary brain tumor, as well as the deadliest.
      Malignant gliomas such as glioblastoma multiforme (GBM) present some of the
      greatest challenges in the management of cancer patients worldwide, despite
      notable recent achievements in oncology. Even with aggressive surgical resections
      using state-of-the-art preoperative and intraoperative neuroimaging, along with
      recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients
      remains dismal: survival after diagnosis is about 1 year. Established prognostic
      factors are limited, but include age, Karnofsky performance status, mini-mental
      status examination score, O6-methylguanine methyltransferase promoter methylation
      and extent of surgery. Standard treatment includes resection of > 95% of the
      tumor, followed by concurrent chemotherapy and radiotherapy. Nevertheless, GBM
      research is being conducted worldwide at a remarkable pace, in the laboratory and
      at the bedside, with some of the more recent promising studies focused on
      identification of aberrant genetic events and signaling pathways to develop
      molecular-based targeted therapies, tumor stem cell identification and
      characterization, modulation of tumor immunological responses and understanding
      of the rare long-term survivors. With this universally fatal disease, any small
      breakthrough will have a significant impact on survival and provide hope to the
      thousands of patients who receive this diagnosis annually. This review describes
      the epidemiology, clinical presentation, pathology and tumor immunology, with a
      focus on understanding the molecular biology that underlies the current targeted
      therapeutics being tested.

PMID- 19409031
TI  - Targeting the eicosanoid pathway in non-small-cell lung cancer.
AB  - Multiple lines of evidence suggest that cyclooxygenase-2 (COX-2) upregulation is
      an early event in the development of non-small-cell lung cancer. Preclinical data
      indicate tumors with upregulation of COX-2 synthesize high levels of
      prostaglandin E2 (PGE2), which in turn are associated with increased production
      of proangiogenic factors and enhanced metastatic potential. These findings
      indicate that an increase in COX-2 expression may play a significant role in the
      development and growth of lung cancers and possibly with the acquisition of an
      invasive and metastatic phenotype. Consequently, inhibitors of COX-2 are being
      studied for their chemopreventative and therapeutic effects in individuals at
      high risk for lung cancer and patients with established cancers.

PMID- 19409035
TI  - Up-regulation of alkaline phosphatase expression in human primary osteoblasts by
      cocultivation with primary endothelial cells is mediated by p38 mitogen-activated
      protein kinase-dependent mRNA stabilization.
AB  - For the regeneration of bone in tissue engineering applications, it is essential
      to provide cues that support neovascularization. This can be achieved by cell
      based therapies using mature endothelial cells (ECs) or endothelial progenitor
      cells. In this context, ECs were used in various in vivo studies in combination
      with primary osteoblasts to enhance neovascularization of bone grafts. In a
      previous study, we have shown that cocultivation of human primary ECs and human
      primary osteoblasts (hOBs) leads to a cell contact-dependent up-regulation of
      alkaline phosphatase (ALP) expression in osteoblasts, indicating that
      cocultivated ECs may support osteogenic differentiation and osteoblastic cell
      functions. In the present study, we investigated this effect in more detail,
      revealing a time and cell number dependency of EC-mediated up-regulation of the
      early osteoblastic marker ALP, whereas osteocalcin, a late marker of
      osteogenesis, was down-regulated. The effect on ALP expression was bidirectional
      specific for both cell types. Functional inhibition of gap junctional
      communication between ECs and hOBs by 18alpha-glycyrrhetinic acid had only a weak
      suppressive effect on EC-mediated ALP up-regulation. In contrast, inhibition of
      p38 mitogen-activated protein kinase nearly completely prevented the EC-mediated
      stimulation of osteoblastic ALP expression. To investigate the molecular
      mechanism underlying the ALP up-regulation, we examined the effect of EC
      cocultivation on osteoblastic ALP promoter activity as well as mRNA stability.
      Cocultivation of ECs with hOBs significantly elevated the half-life of
      osteoblastic ALP mRNA without affecting its promoter activity. In summary, our
      data show that EC-mediated up-regulation of osteoblastic ALP expression is cell
      type specific and is posttranscriptionally regulated via p38 mitogen-activated
      protein kinase-dependent mRNA turn-over.

PMID- 19409034
TI  - A rapid, quantitative method for assessing axonal extension on biomaterial
      platforms.
AB  - Measuring outgrowth of neuronal explants is critical in evaluating the ability of
      a biomaterial to act as a permissive substrate for neuronal adhesion and growth.
      Previous methods lack the ability to quantify robust outgrowth, or lack the
      capacity to quantify growth on opaque substrates because they exploit the
      transparent nature of culture dishes to segregate neuronal processes from an
      image background based on color intensity. In this study, we sought to
      investigate the ability of opaque silica sol-gel materials to facilitate axonal
      outgrowth; therefore, a method was developed for quantifying outgrowth of
      neurites from dorsal root ganglion explants on these unique surfaces. Dorsal root
      ganglia were isolated from stage-nine chick embryos and cultured for 48 h on sol
      gel materials presenting agarose and chitosan polysaccharides individually or in
      combination. Explants were then imaged, and basic image analysis software was
      used by three independent observers to obtain axonal length and axonal area
      measurements. Robust axon length and axonal spread measurements for ganglia
      cultured on agarose-chitosan sol-gel matrices yield an estimate of strong neural
      compatibility for these substrates over silica matrices presenting no
      polysaccharides, or silica matrices presenting chitosan or agarose individually.
      We suggest that this simple protocol for quantifying material biocompatibility
      offers an analysis strategy that can be used universally to the same end.

PMID- 19409037
TI  - 111In-labeled immunoconjugates (ICs) bispecific for the epidermal growth factor
      receptor (EGFR) and cyclin-dependent kinase inhibitor, p27Kip1.
AB  - OBJECTIVE: Probing intranuclear proteins in breast cancer (BC) cells by using
      radiolabeled antibodies is restricted by delivery barriers presented by cell and
      nuclear membranes. Our aim was to construct immunoconjugates (ICs) bispecific for
      epidermal growth factor receptors (EGFRs) and the intranuclear cyclin-dependent
      kinase inhibitor (CDKI) p27(Kip1) modified with nuclear-localizing sequences
      (NLSs) to facilitate their nuclear uptake following EGFR-mediated
      internalization. METHODS: Bispecific ICs were constructed by first modifying EGF
      with peptides [GGPKKKRKVGYGCG] harboring NLS from SV-40 large T-antigen
      (underlined), then conjugating NLS-EGF to anti-p27(Kip1) antibodies through an
      extended PEO(12)-maleimide linker (Compound 1). Analogous ICs were constructed by
      using mouse IgG (Compound 2), a disrupted NLS (Compound 3) or omission of the EGF
      moiety (Compound 4). Binding to EGFR on MDA-MB-468, H2N, or HR2 BC cells and to
      p27(Kip1) in HELA cell lysate was measured. Internalization and nuclear
      importation were evaluated. Retention of the ICs in H2N or trastuzumab
      (Herceptin)-resistant HR2 cells exposed to trastuzumab to modulate p27(Kip1)
      expression with/without coexposure to the IGF-1 receptor kinase inhibitor,
      AG1024, was determined. RESULTS: Trastuzumab (10 microg/mL) unexpectedly
      decreased p27(Kip1) expression by 1.7-2.4-fold in H2N or HR2 cells. Conjugation
      of EGF to anti-p27(Kip1) antibodies (Compound 1) decreased the binding affinity
      of the ICs 7-fold toward EGFR and p27(Kip1). All ICs bound EGFR on MDA-MB-468
      cells except Compound 4. Compound 1 was internalized into H2N cells over 48 hours
      and Compound 2 exhibited 1.6-fold greater nuclear importation in H2N or MDA-MB
      468 cells than Compound 3. There was a significantly lower retention of Compound
      1 in H2N cells exposed to trastuzumab, compared to unexposed cells, corresponding
      to decreased p27(Kip1), but in HR2 cells, diminished retention was observed only
      when these cells were coexposed to trastuzumab and AG]024. CONCLUSION: We
      conclude that (111)In-labeled bispecific ICs were constructed that specifically
      bound EGFR and p27(Kip1). These ICs were internalized into BC cells expressing
      EGFR and HER2 and imported into the nucleus. Their decreased retention by cells
      with trastuzumab-modulated p27(Kip1) suggests that they may be useful for probing
      this CDKI by imaging.

PMID- 19409036
TI  - Affinity and avidity in antibody-based tumor targeting.
AB  - Many factors contribute to successful tumor targeting by antibodies. Besides
      properties of the tumor tissue and general antibody pharmacology, a relationship
      exists between an antibody and its antigen that can shape penetration,
      catabolism, specificity, and efficacy. The affinity and avidity of the binding
      interactions play critical roles in these dynamics. In this work, we review the
      principles that guide models predicting tumor penetration and cellular
      internalization while providing a critical overview of studies aimed at
      experimentally determining the specific role of affinity and avidity in these
      processes. One should gain the perspective that binding affinity can, in part,
      dictate the localization of antibodies in tumors, leading to high concentrations
      in the perivascular space or low concentrations diffused throughout the tumor.
      These patterns can be simply due to the diminution of available dose by binding
      antigen and are complicated by internalization and degradation stemming from slow
      rates of dissociation. As opposed to the trend of simply increasing affinity to
      increase efficacy, novel strategies that increase avidity and broaden specificity
      have made significant progress in tumor targeting.

PMID- 19409038
TI  - A randomized, double-blind, placebo-controlled phase II study of vandetanib plus
      docetaxel/prednisolone in patients with hormone-refractory prostate cancer.
AB  - Vandetanib (ZACTIMA) is a once-daily oral anticancer drug that selectively
      inhibits vascular endothelial growth factor receptor, epidermal growth factor
      receptor, and rearranged during transfection signaling. This randomized (1:1),
      double-blind study evaluated vandetanib (100 mg/day) or placebo in combination
      with docetaxel (D; 75 mg/m(2) every 3 weeks) and prednisolone (P; 2 x 5 mg/day)
      in 86 patients with metastatic hormone-refractory prostate cancer (mHRPC). The
      primary assessment was prostate-specific antigen (PSA) response (confirmed
      reduction of >or=50% from baseline) and a greater number of patients showed a PSA
      response with placebo + DP (67%) versus vandetanib + DP (40%); hazard ratio =
      2.23 (one-sided 80% confidence limit = 2.90; one-sided p = 0.99). More patients
      experienced progression events (disease progression or death from any cause) with
      vandetanib + DP (65%) versus placebo + DP (60%); hazard ratio = 1.13 (one-sided
      80% confidence limit = 1.44; one-sided p = 0.67). The overall incidence of
      adverse events was similar in both groups, although more patients experienced
      adverse events, leading to permanent discontinuation with vandetanib + DP (28%)
      versus placebo + DP (12%). However, the safety and tolerability profile for
      vandetanib was similar to that previously reported; adverse events that occurred
      more frequently in the vandetanib + DP arm were hypertension (14% vs. 2%),
      erythematous rash (14% vs. 2%), and exfoliative rash (12% vs. 2%). In this study
      of patients with mHRPC, vandetanib + DP did not demonstrate any efficacy benefit,
      compared with placebo + DP.

PMID- 19409039
TI  - High-dose intensity pulse interleukin-2 with famotidine in metastatic kidney
      cancer.
AB  - Lymphokine-activated killer cell (LAK) activity against tumor cell lines may be
      induced by intravenous (i.v.) interleukin-2 (IL-2). Daily short infusions
      (pulses) have been developed to decrease toxicity while maintaining the
      anticancer activity of this agent against kidney cancer. The anthihistamine,
      famotidine, may increase IL-2 uptake by the IL-2 receptor on lymphocytes. We have
      treated 12 patients with metastatic kidney cancer, using pulse IL-2 (18 million
      IU/M(2) i.v.) over 15-30 minutes, preceded by famotidine (20 mg I.V. daily for 5
      days) on an oncology inpatient unit. Cycles were repeated every 3 weeks until
      disease progression. Patient characteristics were as follows: 9 males with a
      median age of 66 years (range, 48-74), and median Eastern Cooperative Oncology
      Group performance status of 1; common metastatic sites included in the lungs 9
      and lymph nodes 3. Median number of cycles received was 2 (range, 1-5). The most
      common toxicities were fever, rigors, and hypomagnesemia. Two (2) patients had
      partial responses (17% response rate). Responses occurred in the liver (11.5
      months) and lung, pleura, and lymph nodes (3 months). Pulse IL-2 with famotidine
      shows activity in kidney cancer.

PMID- 19409041
TI  - Tumor accumulation of radiolabeled bevacizumab due to targeting of cell- and
      matrix-associated VEGF-A isoforms.
AB  - PURPOSE: Vascular endothelial growth factor-A (VEGF-A) is one of the most
      important factors inducing angiogenesis in tumors. Nine splice-variant isoforms
      of VEGF-A have been identified, each having different properties. Recently, we
      showed that radiolabeled anti-VEGF monoclonal antibody, bevacizumab, accumulates
      specifically in VEGF-A expressing tumors. In this study, we investigated in a
      nude mouse model which VEGF-isoforms are responsible for tumor accretion.
      MATERIALS AND METHODS: The humanized anti-VEGF-A antibody, A.4.6.1.
      (bevacizumab), was radiolabeled with In-111. The originally VEGF-negative Mel57
      tumor was transfected with different VEGF isoforms (VEGF-121, VEGF-165, and VEGF
      189). The obtained melanoma xenografts specifically expressing different VEGF
      isoforms were used in mice. The bevacizumab uptake was examined in
      biodistribution studies and by gamma-camera imaging. RESULTS: The tumor cell line
      expressing VEGF-121 did not show specific uptake, most likely as a result of the
      fact that this isoform is freely diffusible. Tumors expressing VEGF-165 and -189
      were clearly visualized by using gamma-camera imaging. CONCLUSION: The
      accumulation of radiolabeled bevacizumab in the tumor is due to interaction with
      VEGF-A isoforms that are associated with the tumor cell surface and/or the
      extracellular matrix. Scintigraphic imaging of the expression of these VEGF
      isoforms may thus be useful to predict response to angiogenic therapy.

PMID- 19409042
TI  - Effects of theophylline on radioiodide uptake in MCF-7 breast cancer and NIS gene
      transduced SNU-C5 colon cancer cells.
AB  - BACKGROUND: We investigated whether theophylline has the potential to increase
      radioiodide uptake in nonthyroidal cancer cells. MATERIALS AND METHODS: MCF-7
      cells that express endogenous sodium/iodide symporter (NIS) and SNU-C5 cells
      adenovirally transduced with the human NIS gene (SNU-C5/NIS) were treated with
      10(-7)-2x10(-4) mol/L theophylline for 24 hours before incubation with (125)I,
      and then, radioiodide uptake and retention were measured. NIS expression was
      assessed by immunohistochemistry and Western blot analysis, using an antihuman
      NIS monoclonal antibody. RESULTS: Theophylline at 10(-6)-2x10(-4) mol/L
      significantly and dose dependently augmented radioiodide uptake in MCF-7 cells
      and at 10(-6)-10(-5) mol/L in SNU-C5/NIS cells, without affecting radioiodide
      efflux. Abrogation by KClO(4)(-) demonstrated that the effect of theophylline
      occurred through specific iodide transport. Immunohistochemistry revealed dose
      dependent increases of NIS staining in MCF-7 and SNU-C5/NIS cells by 10(-6)-10(
      4) and 10(-6)-10(-5) mol/L theophylline, respectively. Western blot analysis
      demonstrated similar findings, showing increased expression of NIS on the
      membrane of SNU-C5/NIS and MCF-7 cells by theophylline treatment. CONCLUSIONS:
      Theophylline can augment radioiodide uptake in breast cancer cells and NIS gene
      transduced cancer cells through the upregulation of NIS expression. Therefore,
      further investigations are warranted to explore the potential utility of this
      phenomenon for enhancing radioiodide-based imaging and therapies of NIS gene
      transduced cancer cells.

PMID- 19409040
TI  - Induction of apoptosis by cross-linking antibodies bound to human B-lymphoma
      cells: expression of Annexin V binding sites on the antibody cap.
AB  - There are many reports that cross-linking antibodies (Abs) bound to the surface
      of B-lymphoma cells can induce apoptosis and/or cell death, especially with anti
      CD20 Abs. This study was intended to extend our understanding of these effects.
      To determine if CD20 is a unique target in this respect, or whether Abs to other
      antigens would have similar effects, six Abs were tested, with and without cross
      linking with a secondary Ab, on three target cell lines. We utilized assays that
      distinguish between apoptotic, dead, and viable cells. Two assays were used:
      Annexin V plus propidium iodide, and JC-1 plus SYTOX green (Molecular Probes,
      Eugene, OR). Most of the Abs tested induced a low level of apoptosis and cell
      death in Ramos cells, but not in the other two cell lines (Raji and RL). In
      general, the level of toxicity was correlated with the level of antigen
      expression, with Abs to high-density antigens having the strongest effects.
      However, since the majority of Ramos cells continued to multiply, it is
      questionable whether toxicity at this level can provide a significant clinical
      benefit. Unexpectedly, there was also a population of cells that stained weakly
      with Annexin V. These cells were distinct from classical apoptotic cells, and
      appeared to belong to the viable cell population. In these cells, Annexin V
      stained the region of the Ab cap, in contrast to the ringed staining of classical
      apoptotic cells. IN CONCLUSION: 1) Low-level induction of apoptosis was not
      unique for anti-CD20 Abs, but occurred similarly with other Abs, and 2) results
      of Annexin V staining experiments may need to be reevaluated. Further studies are
      required to explain why Annexin V binding sites are exposed in the region of an
      Ab cap.

PMID- 19409043
TI  - Synthesis and assessment of 99mTc chelate-conjugated alendronate for development
      of specific radiopharmaceuticals.
AB  - Indole-based alendronate (AI) was derived from the condensation reaction of
      indole 3-carboxaldehyde with sodium alendronate (ALN) and was characterized by
      various spectroscopic methods (e.g., ultraviolet, fourier-transform-infrared, and
      liquid chromatography mass spectrometry). The AI was labeled with (99m)Tc and
      radiochemical purity was above 97%, which was ascertained by instant thin-layer
      chromatography, using different solvent conditions, with a specific activity 2-5
      mCi/mg. The receptor ligand assay on human bone cell line Soas-2 showed K(D) =
      0.55 nM. The derivative (AI) was stable, which was determined under physiologic
      conditions up to 24 hours The blood kinetic study showed a biexponential pattern
      as well as quick wash-out from the circulation with varying biologic t(1/2)(F)
      and t(1/2)(S). Excellent-quality radio images were recorded of bone, showing a
      rapid clearance of background activity, at an early visualization at 1.5 hours.
      The excretory pathway of the derivative was through the kidneys, which was
      evidenced by biodistribution studies. Thus, the newly synthesized derivative can
      be considered as a specific bone-seeking agent.

PMID- 19409044
TI  - P-glycoprotein versus MRP1 on transport kinetics of cationic lipophilic
      substrates: a comparative study using [99mTc]sestamibi and [99mTc]tetrofosmin.
AB  - The multidrug resistance (MDR) phenotype in cancer is closely related with the
      overexpression of P-glycoprotein (Pgp) and multidrug resistance protein-1 (MRP1).
      Although conferring resistance to a similar spectrum of drugs, these proteins
      present distinct transport mechanisms and have their own substrates. In this
      work, we compared the functional properties of Pgp and MRP1 in the transport
      kinetics of two cationic lipophilic tracers, [(99m)Tc]sestamibi and
      [(99m)Tc]tetrofosmin, in cellular models of resistance. Cellular transport
      kinetics of both tracers was evaluated in Small-cell lung cancer cell line H69
      and in its drug-resistant sublines, H69LX4 and H69AR, overexpressing Pgp and
      MRP1, respectively. Studies were performed in the absence and in the presence of
      MDR modulators. Kinetic parameters extracted from time-activity curves were
      analyzed through receiver-operating characteristics curve analysis. The uptake
      and the efflux rate of both radiotracers were significantly higher (p < 0.05) in
      sensitive cells. However, MRP1 was more effective than Pgp in removing tracers
      from the intracellular medium. The addition of verapamil and PSC833 significantly
      reduced the efflux rate and restored the accumulation of both tracers in H69LX4
      cells. Only verapamil was effective in the inhibition of MRP1; however, the
      effects were more pronounced with [(99m)Tc]sestamibi, when compared to
      [(99m)Tc]tetrofosmin. Outward transport of radiotracers by MRP1 was dependent on
      the intracellular glutathione levels. We concluded that both tracers can detect
      Pgp- and MRP1-mediated drug resistance, based on transport kinetics; however,
      MRP1 is more effective than Pgp on outward transport of radiotracers. We
      postulate that this finding can be useful to distinguish between the two
      resistance mechanisms.

PMID- 19409045
TI  - Intracranial tumors after radiation therapy: role of 99mTc-tetrofosmin SPECT/CT
      with a hybrid camera.
AB  - BACKGROUND: We evaluated the value of single-photon emission computed
      tomography/computed tomography (SPECT/CT) with a hybrid camera for (99m)Tc
      tetrofosmin (TF) imaging of brain tumors and metastases after radiotherapy.
      METHODS: Forty (40) patients (27 with primary brain tumors and 13 with
      intracranial metastases) were examined 6 months after radiation therapy. SPECT
      images were first evaluated alone and then reinterpreted by adding the anatomic
      (CT) data. Tumor-to-background ratio values were calculated in the nonattenuation
      corrected (T1/B1) and in the CT-attenuation-corrected (T2/B2) images.
      Scintigraphic results were compared with clinical follow-up. RESULTS: SPECT was
      true positive for viable tumor tissue in 21 patients and negative in 19. SPECT/CT
      contributed in 10 of 40 patients (25%): It improved the visualization of lesions
      in the deep temporal lobe, in the orbital region, and in the posterior fossa.
      SPECT/CT was useful in 4 of 8 patients with suspicion of radionecrosis. The
      hybrid camera did not significantly contribute both in patients with a negative
      scan or with large frontotemporal tumors. When all the lesions were considered,
      no significant difference was found between T1/B1 and T2/B2. In small lesions (<2
      cm), T2/B2 was significantly higher (p = 0.04) than T1/B1. When the clinical
      outcome was considered, patients with a significant SPECT/CT contribution had a
      longer average survival than patients with a positive scan, in which the hybrid
      camera did not provide any substantial information (13.3 vs. 8.2 months; p =
      0.0007). CONCLUSIONS: Hybrid SPECT/CT can be useful to better characterize small
      lesions that are deeply located and in areas of high physiologic background.
      Further studies and larger series are needed to more accurately define the
      potential clinical impact of hybrid imaging in patients' management.

PMID- 19409046
TI  - Malignant melanoma therapy by chemotherapy and autoimmunity induced by cytokine.
AB  - PURPOSE: The aim of this study was to evaluate the effect of combining
      dacarbazine (DTIC) and granulocyte/macrophage colony-stimulating factor (GM-CSF)
      with interleukin-2 (IL-2) in patients with advanced malignant melanoma. METHODS:
      Twenty-seven (27) patients with advanced malignant melanoma received dacarbazine
      (500 mg/m(2)/days 1-2, intravenously), GM-CSF (175 ug/m(2)/days 3-6,
      subcutaneously), and interleukin-2 (400 MIU/m(2)/days 7-10, subcutaneously). Each
      treatment cycle required 21 days to completion. RESULTS: Time to progression was
      7-11 months. The total effective rate was 44.4%, and the combination of
      chemotherapy, GM-CSF, and IL-2 had low toxicity. CONCLUSIONS: The combination of
      DTIC with GM-CSF and IL-2 is feasible and possibly efficacious for clinical use.

PMID- 19409047
TI  - Inhibitory effects of VEGF-siRNA mediated by adenovirus on osteosarcoma-bearing
      nude mice.
AB  - As one of the blood-rich malignancies, the growth and metastasis of osteosarcoma
      both depend on its angiogenesis, a procedure in which vascular endothelial growth
      factor (VEGF) acts essentially. Although with the advent of neoadjuvant
      chemotherapy, more aggressive surgical excision and logical therapy strategy, the
      5-year survival rate remains relatively stable at 70%, at best. However,
      antiangiogenic therapeutics, through gene silencing and targeting key sequences,
      probably brings an outlook to the conventional algorithm. In our current
      research, human-specific VEGF-siRNA (small interfering RNA) mediated by
      adenovirus was constructed and a cell line of MG63 was cultured and used to make
      an osteosarcoma-bearing nude mice model. The recombined adenovirus vector of Ad
      VEGF-siRNA could successfully suppress VEGF expression and slow down the
      multiplication of MG63 cells in vivo; likewise, the down regulation of VEGF could
      be detected in vitro of the animal model. Inhibitory effects on osteosarcoma
      growth and blockage of pulmonary metastasis could be observed in the following
      oncotherapy procedure. The study demonstrates potent growth and pulmonary
      metastasis inhibitory effects of VEGF-siRNA on osteosarcoma in vivo and in vitro,
      which could potentially be applicable to the treatment of cancers as an
      antiangiogenic therapeutic in the near future.

PMID- 19409048
TI  - Vascular endothelial growth factor-C siRNA delivered via calcium carbonate
      nanoparticle effectively inhibits lymphangiogenesis and growth of colorectal
      cancer in vivo.
AB  - A nonviral gene carrier, calcium carbonate (CaCO(3))-nanoparticle, was evaluated
      for the efficient in vitro and in vivo delivery of siRNA-targeting vascular
      endothelial growth factor-C (VEGF-C). The chemically synthesized CaCO(3)
      nanoparticle has a 58-nm diameter and a + 28.6-mV positive surface charge. It is
      capable of forming a CaCO(3)-nanoparticle-DNA complex and transferring DNA into
      targeted cells with high transfection efficiency, while effectively protecting
      the encapsulated DNA from degradation. Further, the CaCO(3)-nanoparticle-DNA
      complex has no obvious cytotoxicity for LoVo cells, while a liposome-DNA complex
      exhibited measurable cytotoxicity. LoVo cells transfected with a VEGF-C-targeted
      small interfering RNA (siRNA) via the CaCO(3)-nanoparticle exhibits significantly
      reduced VEGF-C expression, as measured by real-time polymerase chain reaction
      (PCR) and enzyme-linked immunosorbent assay, whereas no decrease in VEGF-C
      expression is observed in cells treated by control transfection. Transfection of
      LoVo cells with VEGF-C siRNA via the CaCO(3)-nanoparticle also dramatically
      suppresses tumor lymphangiogenesis, tumor growth, and regional lymph-node
      metastasis in subcutaneous xenografts. Significant downregulation of VEGF-C
      messenger RNA expression in a subcutaneous xenograft derived from VEGF-C siRNA
      treated LoVo cells was confirmed by real-time PCR, as compared to controls. We
      conclude that the CaCO(3)-nanoparticle is a novel, nonviral system for the
      effective delivery of siRNA for cancer gene therapy.

PMID- 19409049
TI  - Adenovirus-mediated ING4 expression suppresses pancreatic carcinoma cell growth
      via induction of cell-cycle alteration, apoptosis, and inhibition of tumor
      angiogenesis.
AB  - Recent studies have demonstrated that ING4, as a novel member of the ING
      (inhibitor of growth) family, has a potential effect on tumor inhibition via
      multiple pathways. However, adenovirus-mediated ING4 expression in the
      application of gene therapy for pancreatic carcinoma has not been reported. To
      explore its therapeutic effect on human pancreatic carcinoma, we constructed a
      recombinant adenoviral vector, Ad-ING4, expressing the green fluorescent protein
      (GFP) marker gene and the tumor-suppressor gene, humanized ING4 derived from
      murine ING4 with two amino-acid modifications at residues 66 (Arg to Lys) and 156
      (Ala to Thr) by site-directed mutagenesis. We demonstrated that Ad-ING4-mediated
      transfection of PANC-1 human pancreatic carcinoma cells inhibited cell growth,
      altered the cell cycle with S-phase reduction and G2/M phase arrest, induced
      apoptosis, and downregulated interleukin (IL)-6 and IL-8 expression of
      transfected tumor cells. In athymic mice bearing the PANC-1 human pancreatic
      tumors, intratumoral injections of Ad-ING4 suppressed the tumor growth,
      downregulated CD34 expression, and reduced the tumor microvessel formation.
      Therefore, this study will provide a framework for future clinical application of
      Ad-ING4 in human pancreatic carcinoma gene therapy.

PMID- 19409050
TI  - The role of dosimetry in the high activity 90Y-ibritumomab tiuxetan regimens: two
      cases of abnormal biodistribution.
AB  - Radioimmunotherapy (RIT) with a commercially available brand of yttrium-90
      ((90)Y)-ibritumomab-tiuxetan at the prescribed activity of 14.8 MBq/kg (0.4
      mCi/kg) represents a complementary approach in the treatment of
      resistant/refractory B-cell non-Hodgkin's lymphoma. A trial based on higher
      activities is ongoing in our institute. In this paper, we report atypical
      pharmacokinetics and liver uptake in 2 patients. Before RIT, all patients
      underwent dosimetry with (111)In-ibritumomab-tiuxetan. Imaging data were analyzed
      to obtain predicted absorbed doses to nontarget organs. Therapy was administered
      only if a 20-Gy-limit dose to normal organs (except red marrow) was guaranteed.
      Both patients we describe showed abnormal liver uptake, increasing for 6 days
      post injection. In patient 1, there was atypical biodistribution in whole-blood
      images at 16 hours, with a prevalent high liver uptake (45% at 20 hours).
      Injected activity (IA%) was above 40% at 26 hours in the liver and lower than 60%
      in the total body. In patient 2, early images showed regular biodistribution.
      Subsequent images showed progressive increase of liver uptake (above 25% of
      percent injected activity at 25 hours). Liver-absorbed doses of 51 and 53 Gy,
      respectively, would have resulted with the administration of the prescribed 56
      MBq/kg. Following these dosimetric results, both patients did not receive the
      planned therapy. These findings support the recommendation to include dosimetry
      in high-dose RIT.

PMID- 19409053
TI  - CD133 as a marker for cancer stem cells: progresses and concerns.
AB  - Increasing evidence supports the cancer stem cell hypothesis, which postulates
      that cancer stem cells are responsible for tumor initiation, metastasis, and
      resistance to treatments. Therefore, they are the cells to target to cure a
      cancer. To study the behavior of cancer stem cells, markers for prospective
      isolation of cancer stem cells are crucial. Recently, CD133 has been used
      extensively as a marker for the identification of stem cells from normal and
      cancerous tissues. Several more recent studies, however, indicate that CD133 are
      expressed in differentiated epithelial cells in various organs, and CD133
      negative cancer cells can also initiate tumors. The findings suggest that CD133
      is not restricted to somatic stem cells and cancer stem cells. However, in many
      cases CD133 may be used in combination with other markers or methods to acquire
      stem cells. In this review, we summarize findings in CD133 expression in various
      tissues and critically discuss its applications in stem cell isolation.

PMID- 19409051
TI  - Small animal PET in oncology: the road from bench to bedside.
AB  - Positron emission tomography (PET) is routinely performed in patients with cancer
      for disease staging, assessment of relapse, and evaluation of therapy response.
      In addition to its well-established value in human malignant diseases, the use of
      special small animal PET (SA-PET) scanners have allowed for accurate assessment
      of small animals bearing human tumors. This application of PET provides whole
      body, noninvasive, functional data of tumor lesions and can be used to assess
      abnormalities in the metabolic pathways of cancer, such as uncontrolled
      proliferation, increased apoptosis, and angiogenesis. Several positron-emitting
      tracers labeled with 18-fluorine and 11-carbon are currently available for PET
      studies to image abnormal biologic pathways of tumors. Moreover, SA-PET can be
      used to evaluate tumor-cell-receptor expression, a sign of tumor cells
      differentiation that is relevant for planning targeted therapies. Another
      advantage of SA-PET is the quantitation capability: Semiquantitation of the tumor
      activity can be performed at each scan and compared in the same animal over time
      to monitor tumor growth or to assess the response to new therapies. This review
      focuses on the applications of SA-PET for the visualization of the
      pathophysiologic pathways of tumor cells.

PMID- 19409055
TI  - Stimulus-dependent correlations in threshold-crossing spiking neurons.
AB  - We consider a threshold-crossing spiking process as a simple model for the
      activity within a population of neurons. Assuming that these neurons are driven
      by a common fluctuating input with gaussian statistics, we evaluate the cross
      correlation of spike trains in pairs of model neurons with different thresholds.
      This correlation function tends to be asymmetric in time, indicating a preference
      for the neuron with the lower threshold to fire before the one with the higher
      threshold, even if their inputs are identical. The relationship between these
      results and spike statistics in other models of neural activity is explored. In
      particular, we compare our model with an integrate-and-fire model in which the
      membrane voltage resets following each spike. The qualitative properties of spike
      cross-correlations, emerging from the threshold-crossing model, are similar to
      those of bursting events in the integrate-and-fire model. This is particularly
      true for generalized integrate-and-fire models in which spikes tend to occur in
      bursts, as observed, for example, in retinal ganglion cells driven by a rapidly
      fluctuating visual stimulus. The threshold-crossing model thus provides a simple,
      analytically tractable description of event onsets in these neurons.

PMID- 19409054
TI  - Quantifying statistical interdependence by message passing on graphs-part II:
      multidimensional point processes.
AB  - Stochastic event synchrony is a technique to quantify the similarity of pairs of
      signals. First, events are extracted from the two given time series. Next, one
      tries to align events from one time series with events from the other. The better
      the alignment, the more similar the two time series are considered to be. In Part
      I, the companion letter in this issue, one-dimensional events are considered;
      this letter concerns multidimensional events. Although the basic idea is similar,
      the extension to multidimensional point processes involves a significantly more
      difficult combinatorial problem and therefore is nontrivial. Also in the
      multidimensional case, the problem of jointly computing the pairwise alignment
      and SES parameters is cast as a statistical inference problem. This problem is
      solved by coordinate descent, more specifically, by alternating the following two
      steps: (1) estimate the SES parameters from a given pairwise alignment; (2) with
      the resulting estimates, refine the pairwise alignment. The SES parameters are
      computed by maximum a posteriori (MAP) estimation (step 1), in analogy to the one
      dimensional case. The pairwise alignment (step 2) can no longer be obtained
      through dynamic programming, since the state space becomes too large. Instead it
      is determined by applying the max-product algorithm on a cyclic graphical model.
      In order to test the robustness and reliability of the SES method, it is first
      applied to surrogate data. Next, it is applied to detect anomalies in EEG
      synchrony of mild cognitive impairment (MCI) patients. Numerical results suggest
      that SES is significantly more sensitive to perturbations in EEG synchrony than a
      large variety of classical synchrony measures.

PMID- 19409056
TI  - Importance of the cutoff value in the quadratic adaptive integrate-and-fire
      model.
AB  - The quadratic adaptive integrate-and-fire model (Izhikevich, 2003 , 2007 ) is
      able to reproduce various firing patterns of cortical neurons and is widely used
      in large-scale simulations of neural networks. This model describes the dynamics
      of the membrane potential by a differential equation that is quadratic in the
      voltage, coupled to a second equation for adaptation. Integration is stopped
      during the rise phase of a spike at a voltage cutoff value V(c) or when it blows
      up. Subsequently the membrane potential is reset, and the adaptation variable is
      increased by a fixed amount. We show in this note that in the absence of a cutoff
      value, not only the voltage but also the adaptation variable diverges in finite
      time during spike generation in the quadratic model. The divergence of the
      adaptation variable makes the system very sensitive to the cutoff: changing V(c)
      can dramatically alter the spike patterns. Furthermore, from a computational
      viewpoint, the divergence of the adaptation variable implies that the time steps
      for numerical simulation need to be small and adaptive. However, divergence of
      the adaptation variable does not occur for the quartic model (Touboul, 2008 ) and
      the adaptive exponential integrate-and-fire model (Brette & Gerstner, 2005 ).
      Hence, these models are robust to changes in the cutoff value.

PMID- 19409057
TI  - Limited stochastic meta-descent for kernel-based online learning.
AB  - To improve the single-run performance of online learning and reinforce its
      stability, we consider online learning with limited adaptive learning rate in
      this letter. The letter extends convergence proofs for NORMA to a range of step
      sizes, then employs support vector learning with stochastic meta-descent (SVMD)
      limited to that range for step size adaptation, so as to obtain an online kernel
      algorithm that combines theoretical convergence guarantees with good practical
      performance. Experiments on different data sets corroborate theoretical results
      well and show that our method is another promising way for online learning.

PMID- 19409058
TI  - Psychiatric implications of hepatitis-C infection.
AB  - Hepatitis-C virus (HCV) has infected an estimated 130 million people worldwide,
      most of whom are chronically infected. Infection is marked by both treatment- and
      non-treatment-related psychiatric symptoms. Symptoms associated with
      antiretroviral therapy, interferon-alpha (IFN-alpha), include acute confusional
      states, delirium, depression, irritability, and even mania. These psychiatric
      symptoms are further complicated by the high rate of substance abuse and comorbid
      HIV infection inherent to this population. Even in the absence of IFN-alpha
      therapy, comorbid depression, cognitive decline, and especially fatigue are
      common in patients suffering HCV. These comorbidities have significant effects on
      both treatments and outcomes, and thus are reviewed herein.

PMID- 19409059
TI  - A new conceptual understanding of brain function: basic mechanisms of brain
      initiated normal and pathological behaviors.
AB  - This article attempts to show why classical conceptual views of the brain that
      can be found in any neuroscience textbook are not capable of providing an
      adequate explanation of brain-initiated normal and pathological behaviors and why
      the classical view should therefore be replaced with a new concept of the brain.
      The major reason for the inadequacy of the classical model is its explanation of
      the relationship between structure and function in the brain. This article
      introduces a new brain concept based on two discoveries: the discovery of the
      neural network computational principle and the discovery of the generic
      functional organization of hierarchical neural optimal control systems. A neural
      optimal control system is a learning system that possesses a model of the
      behavior of its controlled object. A hierarchy of neural optimal control systems
      is functionally organized in such a way that a higher level neural optimal
      control system treats a lower one as its controlled object and creates a model of
      its behavior. The ability of the new conceptual brain model to explain brain
      mechanisms of normal and pathological behaviors is demonstrated through the
      examples of spinal reflexes and central pattern generators, the cerebellum,
      skeletomotor cortico-basal ganglia-thalamocortical loop, and Parkinson's disease
      and some other brain disorders. In this article, a new understanding of the
      relationship between structure and function in the brain is introduced. This
      article also discusses organizational and educational changes in the
      neurosciences that may be necessary to accelerate a broad acceptance of this new
      concept of the brain.

PMID- 19409060
TI  - Statistical nuclear texture analysis in cancer research: a review of methods and
      applications.
AB  - In digital pathology, the field of nuclear texture analysis gives information
      about the spatial arrangement of the pixel gray levels in a digitized microscopic
      nuclear image, providing statistical texture measures that may be used as
      quantitative tools for diagnosis and prognosis of human cancer. In the present
      work, we have reviewed nuclear texture analysis in human cancer research, with
      emphasis on (i) statistical texture analysis methods, (ii) methods for feature
      evaluation and feature set selection, (iii) classification methods and error
      estimation, and (iv) the recent literature in the field, focusing on diagnosis-
      and prognosis-related applications. The application study covers the period from
      1995 to 2007. In order to find nuclear features that discriminate robustly
      between cases from different diagnostic or prognostic classes, a statistical
      evaluation of features must be performed, and this demands careful experimental
      design. The present review reveals that it is quite common to evaluate a large
      number of features on a limited learning set of clinical material, without
      testing the chosen classifier on an independent validation data set. This easily
      leads to overoptimistic results. Out of 160 papers, we found only 30 papers in
      which the classifier was evaluated on an independent validation data set. Even in
      these studies, some good results have been hampered by small validation groups.
      However, it is encouraging to note that those publications meeting the
      requirements of an optimal study are generally showing good results. Thus, it is
      well documented that nuclear texture analysis is showing promising results as a
      novel diagnostic and/or prognostic marker. Hopefully, we will soon see that these
      promising studies will be replicated in large, prospective, multicenter trials.

PMID- 19409061
TI  - Single-cell gel (comet) assay as a promising tool for the detection of DNA damage
      induced by compounds used in dental practice: the oral cancer risk assessment.
AB  - Taking into consideration genetic damage plays an important role in oral
      carcinogenesis, the purpose of this article is to provide an overview on the
      application of single-cell gel (comet) assay as a promising tool for the
      detection of DNA damage induced by some compounds used in dental practice as far
      as to assess the oral cancer risk. The single-cell gel (comet) assay is a
      microgel electrophoresis technique able to detect DNA damage at the level of
      single cells. In the alkaline version, which is mainly used, DNA single-strand
      breaks, DNA double-strand breaks, alkali-labile sites, and single-strand breaks
      containing incomplete excision repair sites cause increased DNA migration.
      Therefore, this interesting methodology estimates the risk of these substances
      with respect to genotoxicity, and will be added to those used for regulatory
      purposes in improving oral health and preventing oral carcinogenesis.

PMID- 19409062
TI  - The membrane-bound mucins: how large O-glycoproteins play key roles in epithelial
      cancers and hold promise as biological tools for gene-based and immunotherapies.
AB  - Membrane-bound mucins belong to an ever-increasing family of O-glycoproteins that
      share a structure conserved throughout evolution. Typically, membrane-bound
      mucins contain a long extracellular domain, a hydrophobic transmembrane domain,
      and a short cytoplasmic tail. They are modular proteins and have a structural
      organization containing Pro/ Thr/Ser-rich O-glycosylated domains and EGF-like
      domains. The biological roles of mucins arise from their structures. MUC1 and
      MUC4 modulate biological properties of the cell, alter its behavior and modulate
      cell signaling pathways associated with tumorigenesis. Altered expression and
      post-translational modifications confer an important role to MUC1 and MUC4 in
      tumor progression, metastasis, and cancer cell chimioresistance. Moreover,
      increasing knowledge about their animal counterparts has made possible a greater
      understanding of their pathophysiological role in vivo. Most biological functions
      attributed to MUC4 are based on the structural homology with its rat homologue.
      From these results, the development of new biological tools targeting mucins has
      been increasing and the recent attention given to these complex molecules may
      bring hope for improved cancer treatments in the future. This review discusses
      the structure/function of MUC1 and MUC4 membrane-bound mucins in relation to
      cancer cell behavior and cell signaling pathways associated with tumorigenesis,
      as well as their potential as biological tools for gene therapy and immunotherapy
      approaches.

PMID- 19409064
TI  - Balanced gradient boosting from imbalanced data for clinical outcome prediction.
AB  - In clinical outcome prediction, such as disease diagnosis and prognosis, it is
      often assumed that the class, e.g., disease and control, is equally distributed.
      However, in practice we often encounter biological or clinical data whose class
      distribution is highly skewed. Since standard supervised learning algorithms
      intend to maximize the overall prediction accuracy, a prediction model tends to
      show a strong bias toward the majority class when it is trained on such
      imbalanced data. Therefore, the class distribution should be incorporated
      appropriately to learn from imbalanced data. To address this practically
      important problem, we proposed balanced gradient boosting (BalaBoost) which
      reformulates gradient boosting to avoid the overfitting to the majority class and
      is sensitive to the minority class by making use of the equal class distribution
      instead of the empirical class distribution. We applied BalaBoost to cancer
      tissue diagnosis based on miRNA expression data, premature death prediction for
      diabetes patients based on biochemical and clinical variables and tumor grade
      prediction of renal cell carcinoma based on tumor marker expressions whose class
      distribution is highly skewed. Experimental results showed that BalaBoost
      outperformed the representative supervised learning algorithms, i.e., gradient
      boosting, Random Forests and Support Vector Machine. Our results led us to the
      conclusion that BalaBoost is promising for clinical outcome prediction from
      imbalanced data.

PMID- 19409065
TI  - Univariate shrinkage in the cox model for high dimensional data.
AB  - We propose a method for prediction in Cox's proportional model, when the number
      of features (regressors), p, exceeds the number of observations, n. The method
      assumes that the features are independent in each risk set, so that the partial
      likelihood factors into a product. As such, it is analogous to univariate
      thresholding in linear regression and nearest shrunken centroids in
      classification. We call the procedure Cox univariate shrinkage and demonstrate
      its usefulness on real and simulated data. The method has the attractive property
      of being essentially univariate in its operation: the features are entered into
      the model based on the size of their Cox score statistics. We illustrate the new
      method on real and simulated data, and compare it to other proposed methods for
      survival prediction with a large number of predictors.

PMID- 19409066
TI  - Multilevel comparison of dendrograms: a new method with an application for
      genetic classifications.
AB  - Procedures are currently available for the evaluation of hierarchical
      classifications of produce tree dissimilarities or consensus dendrograms. Some
      tests of cluster validity operate by comparing all possible partitions from a
      tree with a reference partition. We propose an exhaustive search procedure to
      compare all partitions from one dendrogram with all partitions derived from the
      other to detect hierarchical levels at which the two dendrograms show maximum
      agreement. The method is illustrated using RAPD and microsatellite data in order
      to detect clones in reed populations. The utility of our approach is its ability
      to reveal extra information in different genetic data sets which would be hidden
      otherwise. The method is also useful in any field of science where hierarchical
      clustering is the main research tool and comparison of results is an objective.
      Artificial and actual dendrograms, together with randomly simulated trees were
      used to compare the performance of five classical coefficients of partition
      dissimilarity. The simulations showed that when meaningful group structure is
      lacking, then the five coefficients are in full disagreement, but they perform
      similarly otherwise.

PMID- 19409067
TI  - Weighted multiple hypothesis testing procedures.
AB  - Multiple hypothesis testing is commonly used in genome research such as genome
      wide studies and gene expression data analysis (Lin, 2005). The widely used
      Bonferroni procedure controls the family-wise error rate (FWER) for multiple
      hypothesis testing, but has limited statistical power as the number of hypotheses
      tested increases. The power of multiple testing procedures can be increased by
      using weighted p-values (Genovese et al., 2006). The weights for the p-values can
      be estimated by using certain prior information. Wasserman and Roeder (2006)
      described a weighted Bonferroni procedure, which incorporates weighted p-values
      into the Bonferroni procedure, and Rubin et al. (2006) and Wasserman and Roeder
      (2006) estimated the optimal weights that maximize the power of the weighted
      Bonferroni procedure under the assumption that the means of the test statistics
      in the multiple testing are known (these weights are called optimal Bonferroni
      weights). This weighted Bonferroni procedure controls FWER and can have higher
      power than the Bonferroni procedure, especially when the optimal Bonferroni
      weights are used. To further improve the power of the weighted Bonferroni
      procedure, first we propose a weighted Sidak procedure that incorporates weighted
      p-values into the Sidak procedure, and then we estimate the optimal weights that
      maximize the average power of the weighted Sidak procedure under the assumption
      that the means of the test statistics in the multiple testing are known (these
      weights are called optimal Sidak weights). This weighted Sidak procedure can have
      higher power than the weighted Bonferroni procedure. Second, we develop a
      generalized sequential (GS) Sidak procedure that incorporates weighted p-values
      into the sequential Sidak procedure (Scherrer, 1984). This GS idak procedure is
      an extension of and has higher power than the GS Bonferroni procedure of Holm
      (1979). Finally, under the assumption that the means of the test statistics in
      the multiple testing are known, we incorporate the optimal Sidak weights and the
      optimal Bonferroni weights into the GS Sidak procedure and the GS Bonferroni
      procedure, respectively. Theoretical proof and/or simulation studies show that
      the GS Sidak procedure can have higher power than the GS Bonferroni procedure
      when their corresponding optimal weights are used, and that both of these GS
      procedures can have much higher power than the weighted Sidak and the weighted
      Bonferroni procedures. All proposed procedures control the FWER well and are
      useful when prior information is available to estimate the weights.

PMID- 19409068
TI  - Using an interactive journal club to enhance nursing research knowledge
      acquisition, appraisal, and application.
AB  - Nursing practice is intricate and multifaceted. It requires the application of
      current, health-related research. Nurses are expected to employ evidence-informed
      practice in making decisions about the clinical care of their clients. A journal
      club is one method that can help promote an increased awareness of research,
      educating students to critique and use research findings. In this descriptive
      pilot study, the use of a journal club was evaluated. University undergraduate
      nursing students (N=35) across three sites in eastern Canada participated.
      Although the results are limited, participants found the journal club sessions
      enjoyable and beneficial for helping them interpret research findings and apply
      research to clinical practice. More research directed at helping nursing students
      critique and apply research to nursing practice is warranted.

PMID- 19409069
TI  - Comparison of outcomes in a traditional versus accelerated nursing curriculum.
AB  - In this descriptive study, graduates of a traditional baccalaureate nursing
      program were compared with graduates of an accelerated baccalaureate program at
      the same university between 1991 and 2006. A survey was sent to a random sample
      of two groups: traditional baccalaureate graduates and graduates of the
      accelerated program who had previous degrees in another major and completed the
      nursing curriculum in a shorter time frame than the traditional students,
      resulting in a total sample of 73 graduates. Outcome variables included
      demographics, NCLEX passing rates, transitioning to the professional role,
      employment, professional development, certifications and self-reported reasons
      the respondents entered the nursing profession and why they remained. There were
      no statistically significant differences between the two groups on these
      variables. Results of a t-test revealed that the GPA of the accelerated group was
      significantly higher than the traditional group. Future considerations include
      the impact that accelerated program development may have on both the current and
      projected nursing shortage.

PMID- 19409070
TI  - Creating diversity in a baccalaureate nursing program: a case study.
AB  - Minority groups in the United States experience disparity in the health care
      services they receive and in their health related outcomes. Minority healthcare
      providers are more likely to serve minority under-served populations, thus
      addressing this healthcare disparity in an effective culturally competent manner
      (Robert Wood Johnson 2005; Sullivan, 2004). The purpose of the project was to
      increase the number of racial and ethnic minority students who are successfully
      recruited and admitted to the nursing program at Hope College in Holland,
      Michigan. The project involved the identification of perceived barriers to
      increased minority participation in nursing at the college, review of the
      literature to identify evidence-based interventions, and implementation of
      selected interventions to overcome the identified barriers. Implementation and
      evaluation are still on-going but showing early success.

PMID- 19409071
TI  - A second generation of the competency-based approach to nursing education.
AB  - This article describes the renewal of a baccalaureate program in nursing. This
      new program was developed to respond to new challenges presented to the
      profession. A completely new approach was adopted, the competency-based approach
      (CBA), with a constructivist, holistic foundation that we named 'second
      generation CBA.' The CBA theoretical underpinnings are presented, as well as the
      structure and the content of the program with a special focus on the teaching and
      learning strategies. A course on health illustrates the approach. Although no
      rigorous evaluation has been held, comments from students and teachers were
      collected during the implementation process. Assessment of students' competency
      levels remains an important issue.

PMID- 19409072
TI  - Pifithrin-alpha decreases the radioprotective efficacy of a Podophyllum hexandrum
      Himalayan mayapple fraction REC-2006 in HepG2 cells.
AB  - Inhibition of the tumour suppressor p53 by PFT (pifithrin-alpha) promotes p53
      mediated apoptosis and protects against doxorubicin-induced apoptosis. The
      present study was carried out to evaluate the effect of PFT on the
      radioprotective potential of Podophyllum hexandrum fraction (REC-2006) in HepG2
      (p53++) cell line. REC-2006 (10-5 microg/ml) treatment at 2 h before irradiation
      (10 Gy) rendered 80+/-3% protection in HepG2 cells, whereas PFT debilitated the
      radioprotective potential of REC-2006. REC-2006 increased the expression of Hsp70
      (heat-shock protein 70), HSF1 (heat-shock factor 1) and Bcl-2 in irradiated HepG2
      cells, whereas PFT when treated with REC-2006 decreased the expression of Hsp70,
      HSF1 and Bcl-2 in HepG2 cells. REC-2006 facilitated post-irradiation DNA repair
      by pausing cell-cycle progression at G1- and G2-phase, whereas no such cell-cycle
      arrest was observed in irradiated HepG2 cells pretreated with PFT in irradiated
      HepG2 cells. No change was observed in Mdm2 (murine double minute 2) and Ras-GAP
      (Ras-GTPase-activating protein) expression with or without PFT treatment.
      Decrease in the expression of caspase 3 and Bax was observed in HepG2 cells when
      REC-2006 treatment was given 2 h before irradiation; however, PFT treatment
      increased the expression of Bax leading to apoptosis. It can be concluded that
      p53 expression plays a major role in the REC-2006-mediated protection against
      acute irradiation in HepG2 cells. PFT treatment reduced the radioprotective
      efficacy of REC-2006 by inhibiting the expression of HSF1 and Hsp70 and thereby
      the expression of Bcl-2, by up-regulating the cell-cycle-regulatory proteins and
      therefore reducing the span of time for DNA repair and also by inducing Bax
      mediated apoptosis. PFT did not, however, show any effect on p53 regulating
      protein (Mdm2) and pro-survival protein (Ras-GAP).

PMID- 19409073
TI  - Hsp70 is required for optimal cell proliferation in mouse A6 mesoangioblast stem
      cells.
AB  - Mouse Hsp70 (70 kDa heat shock protein) is preferentially induced by heat or
      stress stimuli. We previously found that Hsp70 is constitutively expressed in A6
      mouse mesoangioblast stem cells, but its possible role in these cells and the
      control of its basal transcription remained unexplored. Here we report that in
      the absence of stress, Ku factor is able to bind the HSE (heat shock element)
      consensus sequence in vitro, and in vivo it is bound to the proximal hsp70
      promoter. In addition, we show that constitutive hsp70 transcription depends on
      the co-operative interaction of different factors such as Sp1 (specificity
      protein 1) and GAGA-binding protein with Ku factor, which binds the HSE consensus
      sequence. We used mRNA interference assays to select knockdown cell clones. These
      cells were able to respond to heat stress by producing a large amount of Hsp70,
      and produced the same amount of Hsp70 as that synthesized by stressed A6 cells.
      However, severe Hsp70 knockdown cells had a longer duplication time, suggesting
      that constitutive Hsp70 expression has an effect on the rate of proliferation.

PMID- 19409074
TI  - A historical reflection on the discovery of human retroviruses.
AB  - The discovery of HIV-1 as the cause of AIDS was one of the major scientific
      achievements during the last century. Here the events leading to this discovery
      are reviewed with particular attention to priority and actual contributions by
      those involved. Since I would argue that discovering HIV was dependent on the
      previous discovery of the first human retrovirus HTLV-I, the history of this
      discovery is also re-examined. The first human retroviruses (HTLV-I) was first
      reported by Robert C. Gallo and coworkers in 1980 and reconfirmed by Yorio Hinuma
      and coworkers in 1981. These discoveries were in turn dependent on the previous
      discovery by Gallo and coworkers in 1976 of interleukin 2 or T-cell growth factor
      as it was called then. HTLV-II was described by Gallo's group in 1982. A human
      retrovirus distinct from HTLV-I and HTLV-II in that it was shown to have the
      morphology of a lentivirus was in my mind described for the first time by Luc
      Montagnier in an oral presentation at Cold Spring Harbor in September of 1983.
      This virus was isolated from a patient with lymphadenopathy using the protocol
      previously described for HTLV by Gallo. The first peer reviewed paper by
      Montagnier's group of such a retrovirus, isolated from two siblings of whom one
      with AIDS, appeared in Lancet in April of 1984. However, the proof that a new
      human retrovirus (HIV-1) was the cause of AIDS was first established in four
      publications by Gallo's group in the May 4th issue of Science in 1984.

PMID- 19409075
TI  - Genomic expression dominance in allopolyploids.
AB  - BACKGROUND: Allopolyploid speciation requires rapid evolutionary reconciliation
      of two diverged genomes and gene regulatory networks. Here we describe global
      patterns of gene expression accompanying genomic merger and doubling in inter
      specific crosses in the cotton genus (Gossypium L.). RESULTS: Employing a micro
      array platform designed against 40,430 unigenes, we assayed gene expression in
      two sets of parental diploids and their colchicine-doubled allopolyploid
      derivatives. Up to half of all genes were differentially expressed among
      diploids, a striking level of expression evolution among congeners. In the
      allopolyploids, most genes were expressed at mid-parent levels, but this was
      achieved via a phenomenon of genome-wide expression dominance, whereby gene
      expression was either up- or down-regulated to the level of one of the two
      parents, independent of the magnitude of gene expression. This massive expression
      dominance was approximately equal with respect to direction (up- or down
      regulation), and the same diploid parent could be either the dominant or the
      recessive genome depending on the specific genomic combination. Transgressive up-
      and down-regulation were also common in the allopolyploids, both for genes
      equivalently or differentially expressed between the parents. CONCLUSION: Our
      data provide novel insights into the architecture of gene expression in the
      allopolyploid nucleus, raise questions regarding the responsible underlying
      mechanisms of genome dominance, and provide clues into the enigma of the
      evolutionary prevalence of allopolyploids.

PMID- 19409076
TI  - The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children
      with non-alcoholic fatty liver disease.
AB  - BACKGROUND: Liver fibrosis is a stage of non-alcoholic fatty liver disease
      (NAFLD) which is responsible for liver-related morbidity and mortality in adults.
      Accordingly, the search for non-invasive markers of liver fibrosis has been the
      subject of intensive efforts in adults with NAFLD. Here, we developed a simple
      algorithm for the prediction of liver fibrosis in children with NAFLD followed at
      a tertiary care center. METHODS: The study included 136 male and 67 female
      children with NAFLD aged 3.3 to 18.0 years; 141 (69%) of them had fibrosis at
      liver biopsy. On the basis of biological plausibility, readily availability and
      evidence from adult studies, we evaluated the following potential predictors of
      liver fibrosis at bootstrapped stepwise logistic regression: gender, age, body
      mass index, waist circumference, alanine transaminase, aspartate transaminase,
      gamma-glutamyl-transferase, albumin, prothrombin time, glucose, insulin,
      triglycerides and cholesterol. A final model was developed using bootstrapped
      logistic regression with bias-correction. We used this model to develop the
      'pediatric NAFLD fibrosis index' (PNFI), which varies between 0 and 10. RESULTS:
      The final model was based on age, waist circumference and triglycerides and had a
      area under the receiver operating characteristic curve of 0.85 (95% bootstrapped
      confidence interval (CI) with bias correction 0.80 to 0.90) for the prediction of
      liver fibrosis. A PNFI >or= 9 (positive likelihood ratio = 28.6, 95% CI 4.0 to
      201.0; positive predictive value = 98.5, 95% CI 91.8 to 100.0) could be used to
      rule in liver fibrosis without performing liver biopsy. CONCLUSION: PNFI may help
      clinicians to predict liver fibrosis in children with NAFLD, but external
      validation is needed before it can be employed for this purpose.

PMID- 19409077
TI  - White Tea extract induces lipolytic activity and inhibits adipogenesis in human
      subcutaneous (pre)-adipocytes.
AB  - BACKGROUND: The dramatic increase in obesity-related diseases emphasizes the need
      to elucidate the cellular and molecular mechanisms underlying fat metabolism. To
      investigate how natural substances influence lipolysis and adipogenesis, we
      determined the effects of White Tea extract on cultured human subcutaneous
      preadipocytes and adipocytes. METHODS: For our in vitro studies we used a White
      Tea extract solution that contained polyphenols and methylxanthines. Utilizing
      cultured human preadipocytes we investigated White Tea extract solution-induced
      inhibition of triglyceride incorporation during adipogenesis and possible effects
      on cell viability. In vitro studies on human adipocytes were performed aiming to
      elucidate the efficacy of White Tea extract solution to stimulate lipolytic
      activity. To characterize White Tea extract solution-mediated effects on a
      molecular level, we analyzed gene expression of essential adipogenesis-related
      transcription factors by qRT-PCR and determined the expression of the
      transcription factor ADD1/SREBP-1c on the protein level utilizing
      immunofluorescence analysis. RESULTS: Our data show that incubation of
      preadipocytes with White Tea extract solution significantly decreased
      triglyceride incorporation during adipogenesis in a dose-dependent manner (n =
      10) without affecting cell viability (n = 10). These effects were, at least in
      part, mediated by EGCG (n = 10, 50 MUM). In addition, White Tea extract solution
      also stimulated lipolytic activity in adipocytes (n = 7). Differentiating
      preadipocytes cultivated in the presence of 0.5% White Tea extract solution
      showed a decrease in PPARgamma, ADD1/SREBP-1c, C/EBPalpha and C/EBPdelta mRNA
      levels. Moreover, the expression of the transcription factor ADD1/SREBP-1c was
      not only decreased on the mRNA but also on the protein level. CONCLUSION: White
      Tea extract is a natural source that effectively inhibits adipogenesis and
      stimulates lipolysis-activity. Therefore, it can be utilized to modulate
      different levels of the adipocyte life cycle.

PMID- 19409078
TI  - Satisfaction and quality of life in women who undergo breast surgery: a
      qualitative study.
AB  - BACKGROUND: In cosmetic and reconstructive breast surgery, measurement of patient
      reported outcomes has become increasingly important to research efforts and
      clinical care. We aimed to describe how breast conditions and breast surgery
      impact on patient satisfaction and quality of life. METHODS: We conducted
      qualitative, in-depth interviews with 48 women who had undergone either breast
      reduction (n = 15), breast augmentation (n = 12), or breast reconstruction (n =
      21) surgery in order to begin to build a theoretical understanding of patient
      satisfaction and quality of life in breast surgery patients. Interviews were
      audio-taped, transcribed verbatim and analyzed thematically. RESULTS: The patient
      interviews revealed that breast conditions and breast surgery impact women in the
      following six main areas: satisfaction with breasts; satisfaction with overall
      outcome; psychosocial well-being; sexual well-being; physical well-being; and
      satisfaction with the process of care. We used these six themes to form the basis
      of a conceptual framework of patient satisfaction and quality of life in women
      who undergo breast surgery. CONCLUSION: Our conceptual framework establishes the
      main issues of concern for breast surgery patients. This new framework can be
      used to help develop local guidelines for future clinical assessment, management
      and measurement, establish the validity of the current management strategies, and
      develop evidence-based guidance for the development of new patient reported
      outcome measures for future outcomes research.

PMID- 19409079
TI  - Association of MICA with rheumatoid arthritis independent of known HLA-DRB1 risk
      alleles in a family-based and a case control study.
AB  - INTRODUCTION: The gene MICA encodes the protein major histocompatibility complex
      class I polypeptide-related sequence A. It is expressed in synovium of patients
      with rheumatoid arthritis (RA) and its implication in autoimmunity is discussed.
      We analyzed the association of genetic variants of MICA with susceptibility to
      RA. METHODS: Initially, 300 French Caucasian individuals belonging to 100 RA trio
      families were studied. An additional 100 independent RA trio families and a
      German Caucasian case-control cohort (90/182 individuals) were available for
      replication. As MICA is situated in proximity to known risk alleles of the HLA
      DRB1 locus, our analysis accounted for linkage disequilibrium either by analyzing
      the subgroup consisting of parents not carrying HLA-DRB1 risk alleles with
      transmission disequilibrium test (TDT) or by implementing a regression model
      including all available data. Analysis included a microsatellite polymorphism
      (GCT)n and single-nucleotide polymorphisms (SNPs) rs3763288 and rs1051794.
      RESULTS: In contrast to the other investigated polymorphisms, the non
      synonymously coding SNP MICA-250 (rs1051794, Lys196Glu) was strongly associated
      in the first family cohort (TDT: P = 0.014; regression model: odds ratio [OR]
      0.46, 95% confidence interval [CI] 0.25 to 0.82, P = 0.007). Although the
      replication family sample showed only a trend, combined family data remained
      consistent with the hypothesis of MICA-250 association independent from shared
      epitope (SE) alleles (TDT: P = 0.027; regression model: OR 0.56, 95% CI 0.38 to
      0.83, P = 0.003). We also replicated the protective association of MICA-250A
      within a German Caucasian cohort (OR 0.31, 95% CI 0.1 to 0.7, P = 0.005;
      regression model: OR 0.6, 95% CI 0.37 to 0.96, P = 0.032). We showed complete
      linkage disequilibrium of MICA-250 (D' = 1, r2= 1) with the functional MICA
      variant rs1051792 (D' = 1, r2= 1). As rs1051792 confers differential allelic
      affinity of MICA to the receptor NKG2D, this provides a possible functional
      explanation for the observed association. CONCLUSIONS: We present evidence for
      linkage and association of MICA-250 (rs1051794) with RA independent of known HLA
      DRB1 risk alleles, suggesting MICA as an RA susceptibility gene. However, more
      studies within other populations are necessary to prove the general relevance of
      this polymorphism for RA.

PMID- 19409081
TI  - WISDOM-II: screening against multiple targets implicated in malaria using
      computational grid infrastructures.
AB  - BACKGROUND: Despite continuous efforts of the international community to reduce
      the impact of malaria on developing countries, no significant progress has been
      made in the recent years and the discovery of new drugs is more than ever needed.
      Out of the many proteins involved in the metabolic activities of the Plasmodium
      parasite, some are promising targets to carry out rational drug discovery.
      MOTIVATION: Recent years have witnessed the emergence of grids, which are highly
      distributed computing infrastructures particularly well fitted for embarrassingly
      parallel computations like docking. In 2005, a first attempt at using grids for
      large-scale virtual screening focused on plasmepsins and ended up in the
      identification of previously unknown scaffolds, which were confirmed in vitro to
      be active plasmepsin inhibitors. Following this success, a second deployment took
      place in the fall of 2006 focussing on one well known target, dihydrofolate
      reductase (DHFR), and on a new promising one, glutathione-S-transferase. METHODS:
      In silico drug design, especially vHTS is a widely and well-accepted technology
      in lead identification and lead optimization. This approach, therefore builds,
      upon the progress made in computational chemistry to achieve more accurate in
      silico docking and in information technology to design and operate large scale
      grid infrastructures. RESULTS: On the computational side, a sustained
      infrastructure has been developed: docking at large scale, using different
      strategies in result analysis, storing of the results on the fly into MySQL
      databases and application of molecular dynamics refinement are MM-PBSA and MM
      GBSA rescoring. The modeling results obtained are very promising. Based on the
      modeling results, In vitro results are underway for all the targets against which
      screening is performed. CONCLUSION: The current paper describes the rational drug
      discovery activity at large scale, especially molecular docking using FlexX
      software on computational grids in finding hits against three different targets
      (PfGST, PfDHFR, PvDHFR (wild type and mutant forms) implicated in malaria. Grid
      enabled virtual screening approach is proposed to produce focus compound
      libraries for other biological targets relevant to fight the infectious diseases
      of the developing world.

PMID- 19409080
TI  - Sympathetic-correlated c-Fos expression in the neonatal rat spinal cord in vitro.
AB  - An isolated thoracic spinal cord of the neonatal rat in vitro spontaneously
      generates sympathetic nerve discharge (SND) at ~25 degrees C, but it fails in SND
      genesis at < or = 10 degrees C. Basal levels of the c-Fos expression in the
      spinal cords incubated at < or = 10 degrees C and ~25 degrees C were compared to
      determine the anatomical substrates that might participate in SND genesis. Cells
      that exhibited c-Fos immunoreactivity were virtually absent in the spinal cords
      incubated at < or = 10 degrees C. However, in the spinal cords incubated at ~25
      degrees C, c-Fos-positive cells were found in the dorsal laminae, the white
      matter, lamina X, and the intermediolateral cell column (IML). Cell identities
      were verified by double labeling of c-Fos with neuron-specific nuclear protein
      (NeuN), glial fibrillary acidic protein (GFAP), or choline acetyltransferase
      (ChAT). The c-Fos-positive cells distributed in the white matter and lamina X
      were NeuN-negative or GFAP-positive and were glial cells. Endogenously active
      neurons showing c-Fos and NeuN double labeling were scattered in the dorsal
      laminae and concentrated in the IML. Double labeling of c-Fos and ChAT confirmed
      the presence of active sympathetic preganglionic neurons (SPNs) in the IML.
      Suppression of SND genesis by tetrodotoxin (TTX) or mecamylamine (MECA, nicotinic
      receptor blocker) almost abolished c-Fos expression in dorsal laminae, but only
      mildly affected c-Fos expression in the SPNs. Therefore, c-Fos expression in some
      SPNs does not require synaptic activation. Our results suggest that spinal SND
      genesis is initiated from some spontaneously active SPNs, which are capable of
      TTX- or MECA-resistant c-Fos expression.

PMID- 19409082
TI  - MotifAdjuster: a tool for computational reassessment of transcription factor
      binding site annotations.
AB  - Valuable binding-site annotation data are stored in databases. However, several
      types of errors can, and do, occur in the process of manually incorporating
      annotation data from the scientific literature into these databases. Here, we
      introduce MotifAdjuster http://dig.ipk-gatersleben.de/MotifAdjuster.html, a tool
      that helps to detect these errors, and we demonstrate its efficacy on public data
      sets.

PMID- 19409083
TI  - Systemic analysis of the response of Aspergillus niger to ambient pH.
AB  - BACKGROUND: The filamentous fungus Aspergillus niger is an exceptionally
      efficient producer of organic acids, which is one of the reasons for its
      relevance to industrial processes and commercial importance. While it is known
      that the mechanisms regulating this production are tied to the levels of ambient
      pH, the reasons and mechanisms for this are poorly understood. METHODS: To cast
      light on the connection between extracellular pH and acid production, we
      integrate results from two genome-based strategies: A novel method of genome
      scale modeling of the response, and transcriptome analysis across three levels of
      pH. RESULTS: With genome scale modeling with an optimization for extracellular
      proton-production, it was possible to reproduce the preferred pH levels for
      citrate and oxalate. Transcriptome analysis and clustering expanded upon these
      results and allowed the identification of 162 clusters with distinct
      transcription patterns across the different pH-levels examined. New and
      previously described pH-dependent cis-acting promoter elements were identified.
      Combining transcriptome data with genomic coordinates identified four pH
      regulated secondary metabolite gene clusters. Integration of regulatory profiles
      with functional genomics led to the identification of candidate genes for all
      steps of the pal/pacC pH signalling pathway. CONCLUSIONS: The combination of
      genome-scale modeling with comparative genomics and transcriptome analysis has
      provided systems-wide insights into the evolution of highly efficient
      acidification as well as production process applicable knowledge on the
      transcriptional regulation of pH response in the industrially important A. niger.
      It has also made clear that filamentous fungi have evolved to employ several
      offensive strategies for out-competing rival organisms.

PMID- 19409084
TI  - OpenFLUX: efficient modelling software for 13C-based metabolic flux analysis.
AB  - BACKGROUND: The quantitative analysis of metabolic fluxes, i.e., in vivo
      activities of intracellular enzymes and pathways, provides key information on
      biological systems in systems biology and metabolic engineering. It is based on a
      comprehensive approach combining (i) tracer cultivation on 13C substrates, (ii)
      13C labelling analysis by mass spectrometry and (iii) mathematical modelling for
      experimental design, data processing, flux calculation and statistics. Whereas
      the cultivation and the analytical part is fairly advanced, a lack of appropriate
      modelling software solutions for all modelling aspects in flux studies is
      limiting the application of metabolic flux analysis. RESULTS: We have developed
      OpenFLUX as a user friendly, yet flexible software application for small and
      large scale 13C metabolic flux analysis. The application is based on the new
      Elementary Metabolite Unit (EMU) framework, significantly enhancing computation
      speed for flux calculation. From simple notation of metabolic reaction networks
      defined in a spreadsheet, the OpenFLUX parser automatically generates MATLAB
      readable metabolite and isotopomer balances, thus strongly facilitating model
      creation. The model can be used to perform experimental design, parameter
      estimation and sensitivity analysis either using the built-in gradient-based
      search or Monte Carlo algorithms or in user-defined algorithms. Exemplified for a
      microbial flux study with 71 reactions, 8 free flux parameters and mass
      isotopomer distribution of 10 metabolites, OpenFLUX allowed to automatically
      compile the EMU-based model from an Excel file containing metabolic reactions and
      carbon transfer mechanisms, showing it's user-friendliness. It reliably
      reproduced the published data and optimum flux distributions for the network
      under study were found quickly (<20 sec). CONCLUSION: We have developed a fast,
      accurate application to perform steady-state 13C metabolic flux analysis.
      OpenFLUX will strongly facilitate and enhance the design, calculation and
      interpretation of metabolic flux studies. By providing the software open source,
      we hope it will evolve with the rapidly growing field of fluxomics.

PMID- 19409085
TI  - Weight, physical activity and dietary behavior change in young mothers: short
      term results of the HeLP-her cluster randomized controlled trial.
AB  - BACKGROUND: Preventing weight gain rather than treating established obesity is an
      important economic and public health response to the rapidly increasing rates of
      obesity worldwide. Treatment of established obesity is complex and costly
      requiring multiple resources. Preventing weight gain potentially requires fewer
      resources to reach broad population groups, yet there is little evidence for
      successful interventions to prevent weight gain in the community. Women with
      children are an important target group because of high rates of weight gain and
      the potential to influence the health behaviors in family members. METHODS: The
      aim of this cluster randomized controlled trial was to evaluate the short term
      effect of a community-based self-management intervention to prevent weight gain.
      Two hundred and fifty mothers of young children (mean age 40 years +/- 4.5, BMI
      27.9 kg/m2 +/- 5.6) were recruited from the community in Melbourne, Australia.
      The intervention group (n = 127) attended four interactive group sessions over 4
      months, held in 12 local primary schools in 2006, and was compared to a group (n
      = 123) receiving a single, non-interactive, health education session. Data
      collection included self-reported weight (both groups), measured weight
      (intervention only), self-efficacy, dietary intake and physical activity.
      RESULTS: Mean measured weight decreased significantly in the intervention group (
      0.78 kg 95% CI; -1.22 to -0.34, p < 0.001). Comparing groups using self-reported
      weight, both the intervention and comparison groups decreased weight, -0.75 kg
      (95% CI; -1.57 to 0.07, p = 0.07) and -0.72 kg (95% CI; -1.59 to 0.14 p = 0.10)
      respectively with no significant difference between groups (-0.03 kg, 95% CI; 
      1.32 to 1.26, p = 0.95). More women lost or maintained weight in the intervention
      group. The intervention group tended to have the greatest effect in those who
      were overweight at baseline and in those who weighed themselves regularly.
      Intervention women who rarely self-weighed gained weight (+0.07 kg) and regular
      self-weighers lost weight (-1.66 kg) a difference of -1.73 kg (95% CI; -3.35 to 
      0.11 p = 0.04). The intervention reported increased physical activity although
      the difference between groups did not reach significance. Both groups reported
      replacing high fat foods with low fat alternatives and self-efficacy deteriorated
      in the comparison group only. CONCLUSION: Both a single health education session
      and interactive behavioral intervention will result in a similar weight loss in
      the short term, although more participants in the interactive intervention lost
      or maintained weight. There were small non-significant changes to physical
      activity and changes to fat intake specifically replacing high fat foods with low
      fat alternatives such as fruit and vegetables. Self-monitoring appears to enhance
      weight loss when part of an intervention. TRIAL REGISTRATION:
      ACTRN12608000110381.

PMID- 19409086
TI  - Transcriptional profiling of cattle infected with Trypanosoma congolense
      highlights gene expression signatures underlying trypanotolerance and
      trypanosusceptibility.
AB  - BACKGROUND: African animal trypanosomiasis (AAT) caused by tsetse fly-transmitted
      protozoa of the genus Trypanosoma is a major constraint on livestock and
      agricultural production in Africa and is among the top ten global cattle diseases
      impacting on the poor. Here we show that a functional genomics approach can be
      used to identify temporal changes in host peripheral blood mononuclear cell
      (PBMC) gene expression due to disease progression. We also show that major gene
      expression differences exist between cattle from trypanotolerant and
      trypanosusceptible breeds. Using bovine long oligonucleotide microarrays and real
      time quantitative reverse transcription PCR (qRT-PCR) validation we analysed PBMC
      gene expression in naive trypanotolerant and trypanosusceptible cattle
      experimentally challenged with Trypanosoma congolense across a 34-day infection
      time course. RESULTS: Trypanotolerant N'Dama cattle displayed a rapid and
      distinct transcriptional response to infection, with a ten-fold higher number of
      genes differentially expressed at day 14 post-infection compared to
      trypanosusceptible Boran cattle. These analyses identified coordinated temporal
      gene expression changes for both breeds in response to trypanosome infection. In
      addition, a panel of genes were identified that showed pronounced differences in
      gene expression between the two breeds, which may underlie the phenomena of
      trypanotolerance and trypanosusceptibility. Gene ontology (GO) analysis
      demonstrate that the products of these genes may contribute to increased
      mitochondrial mRNA translational efficiency, a more pronounced B cell response,
      an elevated activation status and a heightened response to stress in
      trypanotolerant cattle. CONCLUSION: This study has revealed an extensive and
      diverse range of cellular processes that are altered temporally in response to
      trypanosome infection in African cattle. Results indicate that the
      trypanotolerant N'Dama cattle respond more rapidly and with a greater magnitude
      to infection compared to the trypanosusceptible Boran cattle. Specifically, a
      subset of the genes analyzed by real time qRT-PCR, which display significant
      breed differences, could collectively contribute to the trypanotolerance trait in
      N'Dama.

PMID- 19409087
TI  - QLT0267, a small molecule inhibitor targeting integrin-linked kinase (ILK), and
      docetaxel can combine to produce synergistic interactions linked to enhanced
      cytotoxicity, reductions in P-AKT levels, altered F-actin architecture and
      improved treatment outcomes in an orthotopic breast cancer model.
AB  - INTRODUCTION: Substantial preclinical evidence has indicated that inhibition of
      integrin linked-kinase (ILK) correlates with cytotoxic/cytostatic cellular
      effects, delayed tumor growth in animal models of cancer, and inhibition of
      angiogenesis. Widely anticipated to represent a very promising therapeutic target
      in several cancer indications, it is increasingly evident that optimal
      therapeutic benefits obtained using ILK targeting strategies will only be
      achieved in combination settings. The purpose of this study was to investigate
      the therapeutic potential of the ILK small molecule inhibitor, QLT0267 (267),
      alone or in combination with chemotherapies commonly used to treat breast cancer
      patients. METHODS: A single end-point metabolic assay was used as an initial
      screen for 267 interactions with selected chemotherapeutic agents. These in vitro
      assays were completed with seven breast cancer cell lines including several which
      over-expressed human epidermal growth factor receptor 2 (Her2). One agent,
      docetaxel (Dt), consistently produced synergistic interactions when combined with
      267. Dt/267 interactions were further characterized by measuring therapeutic
      endpoints linked to phosphorylated protein kinase B (P-AKT) suppression,
      inhibition of vascular endothelial growth factor (VEGF) secretion and changes in
      cytoarchitecture. In vivo efficacy studies were completed in mice bearing
      orthotopic xenografts where tumor growth was assessed by bioluminescence and
      calliper methods. RESULTS: The combination of 267 and Dt resulted in increased
      cytotoxic activity, as determined using an assay of metabolic activity.
      Combinations of cisplatin, doxorubicin, vinorelbine, paclitaxel, and trastuzumab
      produced antagonistic interactions. Further endpoint analysis in cell lines with
      low Her2 levels revealed that the 267/Dt combinations resulted in: a three-fold
      decrease in concentration (dose) of 267 required to achieve 50% inhibition of P
      AKT; and a dramatic disruption of normal filamentous-actin cellular architecture.
      In contrast to Her2-positive cell lines, three-fold higher concentrations of 267
      were required to achieve 50% inhibition of P-AKT when the drug was used in
      combination with Dt. In vivo studies focusing on low Her2-expressing breast
      cancer cells (LCC6) implanted orthotopically demonstrated that treatment with
      267/Dt engendered improved therapeutic effects when compared with mice treated
      with either agent alone. CONCLUSIONS: The findings indicate that the 267/Dt drug
      combination confers increased (synergistic) therapeutic efficacy towards human
      breast cancer cells that express low levels of Her2.

PMID- 19409089
TI  - Continuous venovenous hemofiltration in severely burned patients with acute
      kidney injury: a cohort study.
AB  - INTRODUCTION: Acute kidney injury (AKI) is a common and devastating complication
      in critically ill burn patients with mortality reported to be between 80 and
      100%. We aimed to determine the effect on mortality of early application of
      continuous venovenous hemofiltration (CVVH) in severely burned patients with AKI
      admitted to our burn intensive care unit (BICU). METHODS: We performed a
      retrospective cohort study comparing a population of patients managed with early
      and aggressive CVVH compared with historical controls managed conservatively
      before the availability of CVVH. Patients with total body surface area (TBSA)
      burns of more than 40% and AKI were treated with early CVVH and their outcomes
      compared with a group of historical controls. RESULTS: Overall, the 28-day
      mortality was significantly lower in the CVVH arm (n = 29) compared with controls
      (n = 28) (38% vs. 71%, P = 0.011) as was the in-hospital mortality (62% vs. 86%,
      P = 0.04). In a subgroup of patients in shock, a dramatic reduction in the
      pressor requirement was seen after 24 and 48 hours of treatment. Compared with
      controls (n = 19), significantly fewer patients in the CVVH group (n = 21)
      required vasopressors at 24 hours (100% vs 43%, P < 0.0001) and at 48 hours (94%
      vs 24%, P < 0.0001). In those with acute lung injury (ALI)/acute respiratory
      distress syndrome (ARDS), there was a significant increase from baseline in the
      partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2)
      ratio at 24 hours in the CVVH group (n = 16, 174 +/- 78 to 327 +/- 122, P =
      0.003) but not the control group (n = 20, 186 +/- 64 to 207 +/- 131, P = 0.98).
      CONCLUSIONS: The application of CVVH in adult patients with severe burns and AKI
      was associated with a decrease in 28-day and hospital mortality when compared
      with a historical control group, which largely did not receive any form of renal
      replacement. Clinical improvements were realized in the subgroups of patients
      with shock and ALI/ARDS. A randomized controlled trial comparing early CVVH to
      standard care in this high-risk population is planned.

PMID- 19409088
TI  - The importance of accurate road data for spatial applications in public health:
      customizing a road network.
AB  - BACKGROUND: Health researchers have increasingly adopted the use of geographic
      information systems (GIS) for analyzing environments in which people live and how
      those environments affect health. One aspect of this research that is often
      overlooked is the quality and detail of the road data and whether or not it is
      appropriate for the scale of analysis. Many readily available road datasets, both
      public domain and commercial, contain positional errors or generalizations that
      may not be compatible with highly accurate geospatial locations. This study
      examined the accuracy, completeness, and currency of four readily available
      public and commercial sources for road data (North Carolina Department of
      Transportation, StreetMap Pro, TIGER/Line 2000, TIGER/Line 2007) relative to a
      custom road dataset which we developed and used for comparison. METHODS AND
      RESULTS: A custom road network dataset was developed to examine associations
      between health behaviors and the environment among pregnant and postpartum women
      living in central North Carolina in the United States. Three analytical measures
      were developed to assess the comparative accuracy and utility of four publicly
      and commercially available road datasets and the custom dataset in relation to
      participants' residential locations over three time periods. The exclusion of
      road segments and positional errors in the four comparison road datasets resulted
      in between 5.9% and 64.4% of respondents lying farther than 15.24 meters from
      their nearest road, the distance of the threshold set by the project to
      facilitate spatial analysis. Agreement, using a Pearson's correlation
      coefficient, between the customized road dataset and the four comparison road
      datasets ranged from 0.01 to 0.82. CONCLUSION: This study demonstrates the
      importance of examining available road datasets and assessing their completeness,
      accuracy, and currency for their particular study area. This paper serves as an
      example for assessing the feasibility of readily available commercial or public
      road datasets, and outlines the steps by which an improved custom dataset for a
      study area can be developed.

PMID- 19409090
TI  - Highly quantitative serological detection of anti-cytomegalovirus (CMV)
      antibodies.
AB  - BACKGROUND: Human cytomegalovirus infection is associated with a variety of
      pathological conditions including retinitis, pneumonia, hepatitis and
      encephalitis that may be transmitted congenitally, horizontally and parenterally
      and occurs both as a primary infection and as reactivation in immunocompromised
      individuals. Currently, there is a need for improved quantitative serological
      tests to document seropositivity with high sensitivity and specificity. METHODS:
      Here we investigated whether luciferase immunoprecipitation systems (LIPS) would
      provide a more quantitative and sensitive method for detecting anti-CMV
      antibodies. Four protein fragments of immunodominant regions of CMV antigens
      pp150 and pp65 were generated as Renilla luciferase (Ruc) fusion proteins and
      used in LIPS with two cohorts of CMV positive and negative sera samples
      previously tested by ELISA. RESULTS: Analysis of the antibody responses to two of
      these antigen fragments, pp150-d1 and pp150-d2, revealed geometric mean antibody
      titers in the first cohort that were 100-1000 fold higher in the CMV positive
      sera compared to the CMV negative samples (p < 0.0001) and infection status
      exactly matched the ELISA results for the 46 samples of the first cohort (100%
      sensitivity and 100% specificity). Two additional antigen fragments, pp65-d1 and
      pp65-d2 also showed robust antibody titers in some CMV-infected sera and yielded
      50% and 96% sensitivity, respectively. Analysis of a second cohort of 70 samples
      using a mixture of the 4 antigens, which simplifies data collection and analysis,
      yielded values which correlated well with the sum of the values from the 4
      separate tests (rs = 0.93, p < 0.00001). While comparison of the LIPS results
      from this second cohort with ELISA showed 100% sensitivity, LIPS detected six
      additional CMV positive samples that were not detected by ELISA. Heat map
      analysis revealed that several of the LIPS positive/ELISA negative samples had
      positive LIPS immunoreactivity with 3-4 of the CMV antigens. CONCLUSION: These
      results suggest that LIPS provides a highly robust and quantitative method for
      studying anti-CMV antibodies and has the potential to more accurately document
      CMV infection than standard ELISA.

PMID- 19409091
TI  - Ethnic and geographical differences in HLA associations with the outcome of
      hepatitis C virus infection.
AB  - BACKGROUND: The association of human leukocyte antigen (HLA) genes with the
      outcome of hepatitis C virus (HCV) infection may be modified by ethnic and
      geographical differences. RESULTS: HLA-A, -C, -DRB1 and -DQB1 genotyping were
      performed in a Midwestern American cohort of 105 HCV infected subjects among
      which 49 cleared HCV infection and 56 had persistent viral infection. A new
      protective association of HLA-Cw*05 to HCV infection of all ethnic populations
      was identified (OR = 0.12, 95% CI = 0.01-0.97, P = 0.03). It was surprising that
      HLA-A*02 (P for interaction = 0.02) and HLA-DRB1*12 (P for interaction = 0.05)
      showed statistical interaction with race indicating opposite associations in
      Caucasians (OR = 2.74 for A*02 and 2.15 for DRB1*12) and non-Caucasians (OR =
      0.41 for A*02 and 0.15 for DRB1*12). In addition, HLA-DRB1*01 (OR = 0.26),
      DQB1*05 (OR = 0.23) and the haplotype DRB1*01-DQB1*05 (OR = 0.19) showed strong
      associations with viral clearance in Caucasians. The protective associations of
      A*03 (OR = 0.20) and DQB1*03 (OR = 0.20) were exclusive to non-Caucasians. In
      contrast, DQB1*02 (OR = 2.56, 95% CI = 1.15-7.71, P = 0.02) and the haplotype
      DRB1*07-DQB1*02 (OR = 5.25, 95% CI = 1.04-26.6, P = 0.03) were risk markers in
      Caucasians. CONCLUSION: The associations of HLA-A*02 and HLA-DRB1*12 with HCV
      infection are opposite with different races. HLA-A*03, Cw*05, DRB1*01, DQB1*03
      and DQB1*05 are associated with viral clearance while HLA-DRB1*07 and DQB1*02 are
      risk markers for viral persistence of HCV infection in Midwestern Americans.
      These results reveal ethnically and geographically different distribution of HLA
      genes which are associated with the outcome of HCV infection.

PMID- 19409092
TI  - Developing a model of recovery in mental health.
AB  - BACKGROUND: The recovery process is characterized by the interaction of a set of
      individual, environmental and organizational conditions common to different
      people suffering with a mental health problem. The fact that most of the studies
      have been working with schizophrenic patients we cannot extend what has been
      learned about the process of recovery to other types of mental problem. In the
      meantime, the prevalence of anxiety, affective and borderline personality
      disorders continues to increase, imposing a significant socioeconomic burden on
      the Canadian healthcare system and on the patients, their family and significant
      other 1. The aim of this study is to put forward a theoretical model of the
      recovery process for people with mental health problem schizophrenic, affective,
      anxiety and borderline personality disorders, family members and a significant
      care provider. METHOD AND DESIGN: To operationalize the study, a qualitative,
      inductive design was chosen. Qualitative research open the way to learning -- the
      inside -- about different perspectives and issues people face in their process of
      recovery. The study proposal is involving a multisite study that will be
      conducted in three different cities of the Province of Quebec in Canada:
      Montreal, Quebec and Trois-Rivieres. The plan is to select 108 participants,
      divided into four comparison groups representing four types of mental health
      problem. Each comparison group (n = 27) will be made up of 9 units. Each unit
      will comprise one person with a mental health problem (schizophrenia, affective
      anxiety, and borderline personality disorders. Data will be collected through
      semi-structured open-ended interview. The in-depth qualitative analysis inspired
      from the grounded theory approach will permit the illustration of the recovery
      process. DISCUSSION: The transformation of our Health Care System and the
      importance being put on the people well-being and autonomy development of the
      person who are suffering with mental problem This study protocol follows-up on
      earlier theory-building process that begun with the work of Noiseux 2. The
      contribution of the present study is to increase the comprehension of the concept
      of recovery and to enhance the body of knowledge in that domain. Very few studies
      have examined recovery and the one that did used a descriptive approach which did
      not take into account the perspective of the family members and the caregivers of
      the recovery process.

PMID- 19409093
TI  - Exsanguinating upper GI bleeds due to Unusual Arteriovenous Malformation (AVM) of
      stomach and spleen: a case report.
AB  - BACKGROUND: In this paper we are reporting one case of exsanguinating upper
      gastrointestinal tract (GIT) bleed requiring massive blood transfusion and
      immediate life saving surgery. CASE PRESENTATION: A 30 years old female, 12 weeks
      pregnant was referred to our hospital from the earth-quake affected area of
      Kashmir with history of upper abdominal pain, haematemesis and melaena for one
      week. After stabilizing the patient, upper gastro-intestinal endoscopy was
      performed. It revealed gastric ulcer just distal to the gastro-esophageal
      junction on the lesser curvature. Biopsy from the ulcer edge led to profuse
      spurting of the blood and patient went into state of shock. Immediate
      resuscitation led to rebleeding and recurrence of post haemorrahagic shock.
      CONCLUSION: The patient was immediately explored and total gastrectectomy with
      splenectomy concluded as life saving procedure. A review of literature was
      conducted to make this report possible.

PMID- 19409094
TI  - Disease modifying and antiangiogenic activity of 2-methoxyestradiol in a murine
      model of rheumatoid arthritis.
AB  - BACKGROUND: A critical component of disease progression in rheumatoid arthritis
      (RA) involves neovascularization associated with pannus formation. 2
      methoxyestradiol (2ME2) is a naturally occurring molecule with no known
      physiologic function, although at pharmacologic concentrations it has
      antiproliferative and antiangiogenic activities. We investigated the impact of
      orally administered 2ME2 on the initiation and development of proliferative
      synovitis using the anti-collagen monoclonal antibodies (CAIA) model. METHODS:
      Severe polyarticular arthritis was induced in Balb/c female mice by
      administration of 2 mg of a monoclonal antibody cocktail intravenously into the
      tail vein of mice. Twenty-four hours following monoclonal antibody
      administration, mice were injected with 25 microg of LPS (E. coli strain 0111:B4)
      via the intraperitoneal route. Treatment with 2ME2 (100, 75, 50, 25, 10, 1 mg/kg,
      p.o., daily), or vehicle control began 24 hrs following LPS challenge and
      continued to day 21. Hind limbs were harvested, sectioned and evaluated for DMARD
      activity and general histopathology by histomorphometric analysis and
      immunohistochemistry (vWF staining). In a separate study, different dosing
      regimens of 2ME2 (100 mg/kg; q.d. vs q.w. vs q.w. x 2) were evaluated. The effect
      of treatment with 2ME2 on gene expression of inflammatory cytokines and
      angiogenic growth factors in the joint space was evaluated 5 and 14 days after
      the induction of arthritis. RESULTS: Mice treated with 2ME2 beginning 24 hours
      post anti-collagen monoclonal antibody injection, showed a dose-dependent
      inhibition in mean arthritic scores. At study termination (day 21), blinded
      histomorphometric assessments of sectioned hind limbs demonstrated decreases in
      synovial inflammation, articular cartilage degradation, pannus formation,
      osteoclast activity and bone resorption. At the maximal efficacious dosing
      regimen (100 mg/kg/day), administration of 2ME2 resulted in total inhibition of
      the study parameters and prevented neovascularization into the joint. Examination
      of gene expression on dissected hind limbs from mice treated for 5 or 14 days
      with 2ME2 showed inhibition of inflammatory cytokine message for IL-1beta, TNF
      alpha, IL-6 and IL-17, as well as the angiogenic cytokines, VEGF and FGF-2.
      CONCLUSION: These data demonstrate that in the CAIA mouse model of RA, 2ME2 has
      disease modifying activity that is at least partially attributable to the
      inhibition of neovascular development. Further, the data suggests new mechanistic
      points of intervention for 2ME2 in RA, specifically inhibition of inflammatory
      mediators and osteoclast activity.

PMID- 19409095
TI  - Protocol for the PINCER trial: a cluster randomised trial comparing the
      effectiveness of a pharmacist-led IT-based intervention with simple feedback in
      reducing rates of clinically important errors in medicines management in general
      practices.
AB  - BACKGROUND: Medication errors are an important cause of morbidity and mortality
      in primary care. The aims of this study are to determine the effectiveness, cost
      effectiveness and acceptability of a pharmacist-led information-technology-based
      complex intervention compared with simple feedback in reducing proportions of
      patients at risk from potentially hazardous prescribing and medicines management
      in general (family) practice. METHODS: RESEARCH SUBJECT GROUP: "At-risk" patients
      registered with computerised general practices in two geographical regions in
      England. DESIGN: Parallel group pragmatic cluster randomised trial.
      INTERVENTIONS: Practices will be randomised to either: (i) Computer-generated
      feedback; or (ii) Pharmacist-led intervention comprising of computer-generated
      feedback, educational outreach and dedicated support. PRIMARY OUTCOME MEASURES:
      The proportion of patients in each practice at six and 12 months post
      intervention: - with a computer-recorded history of peptic ulcer being prescribed
      non-selective non-steroidal anti-inflammatory drugs; - with a computer-recorded
      diagnosis of asthma being prescribed beta-blockers; - aged 75 years and older
      receiving long-term prescriptions for angiotensin converting enzyme inhibitors or
      loop diuretics without a recorded assessment of renal function and electrolytes
      in the preceding 15 months. SECONDARY OUTCOME MEASURES; These relate to a number
      of other examples of potentially hazardous prescribing and medicines management.
      ECONOMIC ANALYSIS: An economic evaluation will be done of the cost per error
      avoided, from the perspective of the UK National Health Service (NHS), comparing
      the pharmacist-led intervention with simple feedback. QUALITATIVE ANALYSIS: A
      qualitative study will be conducted to explore the views and experiences of
      health care professionals and NHS managers concerning the interventions, and
      investigate possible reasons why the interventions prove effective, or conversely
      prove ineffective. SAMPLE SIZE: 34 practices in each of the two treatment arms
      would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a 50%
      reduction in error rates for each of the three primary outcome measures in the
      pharmacist-led intervention arm compared with a 11% reduction in the simple
      feedback arm. DISCUSSION: At the time of submission of this article, 72 general
      practices have been recruited (36 in each arm of the trial) and the interventions
      have been delivered. Analysis has not yet been undertaken.

PMID- 19409096
TI  - Ethnomedical survey of Berta ethnic group Assosa Zone, Benishangul-Gumuz regional
      state, mid-west Ethiopia.
AB  - Traditional medicine (TM) has been a major source of health care in Ethiopia as
      in most developing countries around the world. This survey examined the extent
      and factors determining the use of TM and medicinal plants by Berta community.
      One thousand and two hundred households (HHs) and fourteen traditional healers
      were interviewed using semi-structured questionnaires and six focused group
      discussions (FGDs) were conducted. The prevalence of the use of TM in the two
      weeks recall period was 4.6%. The HH economic status was found to have a
      significant effect while the educational level and age of the patients have no
      effect either on the care seeking behavior or choice of care. Taking no action
      about a given health problem and using TM are common in females with low-income
      HHs. Forty plant species belonging to 23 families were reported, each with local
      names, methods of preparation and parts used. This study indicates that although
      the proportion of the population that uses TM may be small it is still an
      important component of the public health care in the study community as
      complementary and alternative medicine.

PMID- 19409097
TI  - PTools: an opensource molecular docking library.
AB  - BACKGROUND: Macromolecular docking is a challenging field of bioinformatics.
      Developing new algorithms is a slow process generally involving routine tasks
      that should be found in a robust library and not programmed from scratch for
      every new software application. RESULTS: We present an object-oriented Python/C++
      library to help the development of new docking methods. This library contains low
      level routines like PDB-format manipulation functions as well as high-level tools
      for docking and analyzing results. We also illustrate the ease of use of this
      library with the detailed implementation of a 3-body docking procedure.
      CONCLUSION: The PTools library can handle molecules at coarse-grained or atomic
      resolution and allows users to rapidly develop new software. The library is
      already in use for protein-protein and protein-DNA docking with the ATTRACT
      program and for simulation analysis. This library is freely available under the
      GNU GPL license, together with detailed documentation.

PMID- 19409098
TI  - Cigarette smoke regulates the expression of TLR4 and IL-8 production by human
      macrophages.
AB  - BACKGROUND: Toll-like receptors (TLRs) are present on monocytes and alveolar
      macrophages that form the first line of defense against inhaled particles. The
      importance of those cells in the pathophysiology of chronic obstructive pulmonary
      disease (COPD) has well been documented. Cigarette smoke contains high
      concentration of oxidants which can stimulate immune cells to produce reactive
      oxygen species, cytokines and chemokines. METHODS: In this study, we evaluated
      the effects of cigarette smoke medium (CSM) on TLR4 expression and interleukin
      (IL)-8 production by human macrophages investigating the involvement of ROS.
      RESULTS AND DISCUSSION: TLR4 surface expression was downregulated on short term
      exposure (1 h) of CSM. The downregulation could be explained by internalization
      of the TLR4 and the upregulation by an increase in TLR4 mRNA. IL-8 mRNA and
      protein were also increased by CSM. CSM stimulation increased intracellular ROS
      production and decreased glutathione (GSH) levels. The modulation of TLR4 mRNA
      and surface receptors expression, IRAK activation, IkappaB-alpha degradation, IL
      8 mRNA and protein, GSH depletion and ROS production were all prevented by
      antioxidants such as N-acetyl-L-cysteine (NAC). CONCLUSION: TLR4 may be involved
      in the pathogenesis of lung emphysema and oxidative stress and seems to be a
      crucial contributor in lung inflammation.

PMID- 19409099
TI  - Puromycin-based vectors promote a ROS-dependent recruitment of PML to nuclear
      inclusions enriched with HSP70 and Proteasomes.
AB  - BACKGROUND: Promyelocytic Leukemia (PML) protein can interact with a multitude of
      cellular factors and has been implicated in the regulation of various processes,
      including protein sequestration, cell cycle regulation and DNA damage responses.
      Previous studies reported that misfolded proteins or proteins containing
      polyglutamine tracts form aggregates with PML, chaperones, and components of the
      proteasome, supporting a role for PML in misfolded protein degradation. RESULTS:
      In the current study, we have identified a reactive oxygen species (ROS)
      dependent aggregation of PML, small ubiquitin-like modifier 1 (SUMO-1), heat
      shock protein 70 (HSP70) and 20S proteasomes in human cell lines that have been
      transiently transfected with vectors expressing the puromycin resistance gene,
      puromycin n-acetyl transferase (pac). Immunofluorescent studies demonstrated that
      PML, SUMO-1, HSP70 and 20S proteasomes aggregated to form nuclear inclusions in
      multiple cell lines transfected with vectors expressing puromycin (puro)
      resistance in regions distinct from nucleoli. This effect does not occur in cells
      transfected with identical vectors expressing other antibiotic resistance genes
      or with vectors from which the pac sequence has been deleted. Furthermore, ROS
      scavengers were shown to ablate the effect of puro vectors on protein aggregation
      in transfected cells demonstrating a dependency of this effect on the redox state
      of transfected cells. CONCLUSION: Taken together we propose that puromycin
      vectors may elicit an unexpected misfolded protein response, associated with the
      formation of nuclear aggresome like structures in human cell lines. This effect
      has broad implications for cellular behavior and experimental design.

PMID- 19409100
TI  - The co-receptor signaling model of HIV-1 pathogenesis in peripheral CD4 T cells.
AB  - HIV-mediated CD4 depletion is the hallmark of AIDS and is the most reliable
      predictor of disease progression. While HIV replication is associated with CD4
      depletion in general, plasma viremia by itself predicts the rate of CD4 loss only
      minimally in untreated patients. To resolve this paradox, I hypothesize the
      existence of a subpopulation of R5X4-signaling viruses. I also suggest that the
      gradual evolution and emergence of this subpopulation are largely responsible for
      the slow depletion of peripheral CD4 T cells.

PMID- 19409101
TI  - Genome-wide identification and characterization of cytochrome P450 monooxygenase
      genes in the ciliate Tetrahymena thermophila.
AB  - BACKGROUND: Cytochrome P450 monooxygenases play key roles in the metabolism of a
      wide variety of substrates and they are closely associated with endocellular
      physiological processes or detoxification metabolism under environmental
      exposure. To date, however, none has been systematically characterized in the
      phylum Ciliophora. T. thermophila possess many advantages as a eukaryotic model
      organism and it exhibits rapid and sensitive responses to xenobiotics, making it
      an ideal model system to study the evolutionary and functional diversity of the
      P450 monooxygenase gene family. RESULTS: A total of 44 putative functional
      cytochrome P450 genes were identified and could be classified into 13 families
      and 21 sub-families according to standard nomenclature. The characteristics of
      both the conserved intron-exon organization and scaffold localization of tandem
      repeats within each P450 family clade suggested that the enlargement of T.
      thermophila P450 families probably resulted from recent separate small
      duplication events. Gene expression patterns of all T. thermophila P450s during
      three important cell physiological stages (vegetative growth, starvation and
      conjugation) were analyzed based on EST and microarray data, and three main
      categories of expression patterns were postulated. Evolutionary analysis
      including codon usage preference, site-specific selection and gene-expression
      evolution patterns were investigated and the results indicated remarkable
      divergences among the T. thermophila P450 genes. CONCLUSION: The
      characterization, expression and evolutionary analysis of T. thermophila P450
      monooxygenase genes in the current study provides useful information for
      understanding the characteristics and diversities of the P450 genes in the
      Ciliophora, and provides the baseline for functional analyses of individual P450
      isoforms in this model ciliate species.

PMID- 19409102
TI  - Activation of cytosolic phospholipase A2 in dorsal root ganglion neurons by
      Ca2+/calmodulin-dependent protein kinase II after peripheral nerve injury.
AB  - BACKGROUND: Peripheral nerve injury leads to a persistent neuropathic pain state
      in which innocuous stimulation elicits pain behavior (tactile allodynia), but the
      underlying mechanisms have remained largely unknown. We have previously shown
      that spinal nerve injury induces the activation of cytosolic phospholipase A2
      (cPLA2) in injured dorsal root ganglion (DRG) neurons that contribute to tactile
      allodynia. However, little is known about the signaling pathway that activates
      cPLA2 after nerve injury. In the present study, we sought to determine the
      mechanisms underlying cPLA2 activation in injured DRG neurons in an animal model
      of neuropathic pain, focusing on mitogen-activated protein kinases (MAPKs) and
      Ca2+/calmodulin-dependent protein kinase II (CaMKII). RESULTS: Pharmacological
      inhibition of either p38 or extracellular signal-regulated kinase (ERK) in the
      injured DRG, which led to suppression of the development of tactile allodynia,
      did not affect cPLA2 phosphorylation and translocation after nerve injury. By
      contrast, a CaMKII inhibitor prevented the development and expression of nerve
      injury-induced tactile allodynia and reduced both the level of cPLA2
      phosphorylation and the number of DRG neurons showing translocated cPLA2 in
      response to nerve injury. Applying ATP to cultured DRG neurons increased the
      level of both phosphorylated cPLA2 and CaMKII in the vicinity of the plasma
      membrane and caused physical association of these two proteins. In addition, ATP
      stimulated cPLA2 and CaMKII phosphorylation were inhibited by both a selective
      P2X3R/P2X2+3R antagonist and a nonselective voltage-dependent Ca2+ channel (VDCC)
      blocker. CONCLUSION: These results suggest that CaMKII, but not MAPKs, has an
      important role in cPLA2 activation following peripheral nerve injury, probably
      through P2X3R/P2X2+3R and VDCCs in primary afferent neurons.

PMID- 19409103
TI  - Correlation of histopathological diagnosis with habits and clinical findings in
      oral submucous fibrosis.
AB  - BACKGROUND: Oral submucous fibrosis is a common oral health problem in India.
      This study was conducted to correlate the histopathological diagnosis with habits
      and clinical findings in patients suffering from oral submucous fibrosis (OSF).
      METHODS: Patients suffering from oral submucous fibrosis from the Departments of
      Otorhinolaryngology and Pathology, Moti Lal Nehru Medical College, Allahabad,
      India were studied from 2004-2008. Detailed information was gathered in a
      pretested proforma. Emphasis was given to the various addictions, clinical
      findings and histological examination was done. RESULTS: Two hundred and thirty
      nine patients were studied, yielding a male to female ratio of 6.8:1. Maximum
      patients were in the 21-30 years age group with a marked male predominance. Of
      these, 197 (82.4%) patients chewed areca nut/dohra, 14 (5.8%) were smokers and 2
      (0.8%) patients were habituated to alcohol. 89 (37.2%) patients reported
      difficulty in opening of the mouth (trismus). 51 (57.4%) patients were found to
      have stage II (2-3 cm) trismus while rest had stage I and III. The buccal mucosa
      was found to be the most commonly involved site. On the basis of
      histopathological examination, 52 (21.7%) were classified as OSF grade I, 75
      (31.3%) patients as grade II and 112 (46.8%) had grade III disease. CONCLUSION:
      The widespread habit of chewing dohra/paan masala is a major risk factor of OSF,
      especially in the younger age group. In this study, an increase in
      histopathological grading was found with severity and duration of addiction
      habit. However no significant correlation was found between clinical staging and
      histopathological grading.

PMID- 19409104
TI  - GSK-3beta phosphorylation of functionally distinct tau isoforms has differential,
      but mild effects.
AB  - BACKGROUND: Tau protein exists as six different isoforms that differ by the
      inclusion or exclusion of exons 2, 3 and 10. Exon 10 encodes a microtubule
      binding repeat, thereby resulting in three isoforms with three microtubule
      binding repeats (3R) and three isoforms that have four microtubule binding
      repeats (4R). In normal adult brain, the relative amounts of 3R tau and 4R tau
      are approximately equal. These relative protein levels are preserved in
      Alzheimer's disease, although in other neurodegenerative tauopathies such as
      progressive supranuclear palsy, corticobasal degeneration and Pick's disease, the
      ratio of 3R:4R is frequently altered. Because tau isoforms are not equally
      involved in these diseases, it is possible that they either have inherently
      unique characteristics owing to their primary structures or that post
      translational modification, such as phosphorylation, differentially affects their
      properties. RESULTS: We have determined the effects of phosphorylation by a
      kinase widely believed to be involved in neurodegenerative processes, glycogen
      synthase kinase-3beta (GSK-3beta), on the microtubule binding and inducer
      initiated polymerization of these isoforms in vitro. We have found that each
      isoform has a unique microtubule binding and polymerization profile that is
      altered by GSK-3beta. GSK-3beta phosphorylation had differential effects on the
      isoforms although there were similarities between isoforms and the effects were
      generally mild. CONCLUSION: These results indicate that tau phosphorylation by a
      single kinase can have isoform specific outcomes. The mild nature of these
      changes, however, makes it unlikely that differential effects of GSK-3beta
      phosphorylation on the isoforms are causative in neurodegenerative disease.
      Instead, the inherent differences in the isoform interactions themselves and
      local conditions in the diseased cells are likely the major determinant of
      isoform involvement in various neurodegenerative disorders.

PMID- 19409105
TI  - Simvastatin ameliorates established pulmonary hypertension through a heme
      oxygenase-1 dependent pathway in rats.
AB  - BACKGROUND: Simvastatin has been shown to ameliorate pulmonary hypertension by
      several mechanisms in experimental animal models. In this study, we hypothesized
      that the major benefits of simvastatin in pulmonary hypertension occur via the
      heme oxygenase-1 pathway. METHODS: Simvastatin (10 mg/kgw/day) was tested in two
      rat models of pulmonary hypertension (PH): monocrotaline administration and
      chronic hypoxia. The hemodynamic changes, right heart hypertrophy, HO-1 protein
      expression, and heme oxygenase (HO) activity in lungs were measured in both
      models with and without simvastatin treatment. Tin-protoporphyrin (SnPP, 20
      micromol/kg w/day), a potent inhibitor of HO activity, was used to confirm the
      role of HO-1. RESULTS: Simvastatin significantly ameliorated pulmonary arterial
      hypertension from 38.0 +/- 2.2 mm Hg to 22.1 +/- 1.9 mm Hg in monocrotaline
      induced PH (MCT-PH) and from 33.3 +/- 0.8 mm Hg to 17.5 +/- 2.9 mm Hg in chronic
      hypoxia-induced PH (CH-PH) rats. The severity of right ventricular hypertrophy
      was significantly reduced by simvastatin in MCT-PH and CH-PH rats. Co
      administration with SnPP abolished the benefits of simvastatin. Simvastatin
      significantly increased HO-1 protein expression and HO activity in the lungs of
      rats with PH; however co-administration of SnPP reduced HO-1 activity only. These
      observations indicate that the simvastatin-induced amelioration of pulmonary
      hypertension was directly related to the activity of HO-1, rather than its
      expression. CONCLUSION: This study demonstrated that simvastatin treatment
      ameliorates established pulmonary hypertension primarily through an HO-1
      dependent pathway.

PMID- 19409106
TI  - An iron-based beverage, HydroFerrate fluid (MRN-100), alleviates oxidative stress
      in murine lymphocytes in vitro.
AB  - BACKGROUND: Several studies have examined the correlation between iron oxidation
      and H(2)O(2) degradation. The present study was carried out to examine the
      protective effects of MRN-100 against stress-induced apoptosis in murine splenic
      cells in vitro. MRN-100, or HydroFerrate fluid, is an iron-based beverage
      composed of bivalent and trivalent ferrates. METHODS: Splenic lymphocytes from
      mice were cultured in the presence or absence of MRN-100 for 2 hrs and were
      subsequently exposed to hydrogen peroxide (H(2)O(2) ) at a concentration of 25
      microM for 14 hrs. Percent cell death was examined by flow cytometry and trypan
      blue exclusion. The effect of MRN-100 on Bcl-2 and Bax protein levels was
      determined by Western blot. RESULTS: Results show, as expected, that culture of
      splenic cells with H(2)O(2) alone results in a significant increase in cell death
      (apoptosis) as compared to control (CM) cells. In contrast, pre-treatment of
      cells with MRN-100 followed by H(2)O(2) treatment results in significantly
      reduced levels of apoptosis.In addition, MRN-100 partially prevents H(2)O(2) 
      induced down-regulation of the anti-apoptotic molecule Bcl-2 and upregulation of
      the pro-apoptotic molecule Bax. CONCLUSION: Our findings suggest that MRN-100 may
      offer a protective effect against oxidative stress-induced apoptosis in
      lymphocytes.

PMID- 19409107
TI  - Experience with impacted upper ureteral stones; should we abandon using semirigid
      ureteroscopes and pneumatic lithoclast?
AB  - INTRODUCTION: The AUA/EAU Ureteral Stones Guideline Panel reported that the stone
      free rate for the proximal ureteral stones is around 81% when treated by either
      SWL or ureteroscopy (URS).Complication rates, most notably ureteral perforation
      and long-term complications of URS such as stricture formation rates, have been
      reduced to < 5%. Moreover, impacted ureteral calculi are more difficult to
      fragment with SWL because of the lack of natural expansion space for stones, this
      result in a situation that is better managed by ureteroscopy. The aim of this
      study is to assess the efficacy, safety, and complications of impacted upper
      ureteral stone disintegration using semirigid ureteroscopes and pneumatic
      lithotripsy. METHODS: We retrospectively analyzed the records of 267 consecutive
      patients with impacted upper ureteral stones (9-20 mm) who were treated by
      semirigid ureteroscopes and pneumatic disintegration. The efficacy of treatment
      was estimated using the stone-free rate and all treatment related complications
      were analyzed. RESULTS: Except for 24 cases where the stone migrated to the
      kidney, the stone was successfully treated ureteroscopically, with a low rate of
      minimal complications such as mild hematuria (18.4%), short term low grade fever
      (13.5%). Only 3 patients (1.1%) had high grade fever and none had post operative
      stricture. CONCLUSION: The use of semirigid URS and pneumatic lithotripsy in
      impacted upper ureteral stones in experienced hands has very satisfactory results
      with minimal complications. When Holmium laser and flexible URS are not
      available, semirigid URS and pneumatic lithotripsy is a good alternative that
      shouldn't, yet, be abandoned.

PMID- 19409108
TI  - Australian clinicians and chemoprevention for women at high familial risk for
      breast cancer.
AB  - OBJECTIVES: Effective chemoprevention strategies exist for women at high risk for
      breast cancer, yet uptake is low. Physician recommendation is an important
      determinant of uptake, but little is known about clinicians' attitudes to
      chemoprevention. METHODS: Focus groups were conducted with clinicians at five
      Family Cancer Centers in three Australian states. Discussions were recorded,
      transcribed and analyzed thematically. RESULTS: Twenty three clinicians,
      including genetic counselors, clinical geneticists, medical oncologists, breast
      surgeons and gynaecologic oncologists, participated in six focus groups in 2007.
      The identified barriers to the discussion of the use of tamoxifen and raloxifene
      for chemoprevention pertained to issues of evidence (evidence for efficacy not
      strong enough, side-effects outweigh benefits, oophorectomy superior for mutation
      carriers), practice (drugs not approved for chemoprevention by regulatory
      authorities and not government subsidized, chemoprevention not endorsed in
      national guidelines and not many women ask about it), and perception (clinicians
      not knowledgeable about chemoprevention and women thought to be opposed to
      hormonal treatments). CONCLUSION: The study demonstrated limited enthusiasm for
      discussing breast cancer chemoprevention as a management option for women at high
      familial risk. Several options for increasing the likelihood of clinicians
      discussing chemoprevention were identified; maintaining up to date national
      guidelines on management of these women and education of clinicians about the
      drugs themselves, the legality of "off-label" prescribing, and the actual costs
      of chemopreventive medications.

PMID- 19409109
TI  - Association of IL-10 and IL-10Rbeta gene polymorphisms with graft-versus-host
      disease after haematopoietic stem cell transplantation from an HLA-identical
      sibling donor.
AB  - BACKGROUND: Extensive allelic matching in the human leukocyte antigen (HLA) genes
      is regarded as a prerequisite for good clinical success of allogeneic
      haematopoietic stem cell transplantation (HSCT). Also other genetic factors can
      be assumed to play a role in preventing and controlling the complications
      associated with allogeneic HSCT, in particular graft-versus-host disease (GvHD).
      Interleukin-10 (IL-10) and its receptor (IL-10R), key regulators of the immune
      response, are among these candidates. We studied the association of IL-10 and IL
      10Rbeta gene polymorphisms with the occurrence of GvHD in 309 HLA-identical
      sibling donor and recipient pairs. RESULTS: The difference in genotypic IL-10
      production between patient and donor in combination with patient IL-10Rbeta A/A
      genotype predisposed strongly to acute GvHD (OR = 7.15, p = 0.000023). On the
      other hand, a combination of same genotypic IL-10 production with patient IL
      10Rbeta A/A genotype protected from chronic GvHD (OR = 0.407, p = 0.0097).
      CONCLUSION: Our results suggest that IL-10 and IL-10Rbeta genes have a
      synergistic effect on the risk of GvHD.

PMID- 19409110
TI  - Physical activity, energy requirements, and adequacy of dietary intakes of older
      persons in a rural Filipino community.
AB  - BACKGROUND: Aging is a process associated with physiological changes such as in
      body composition, energy expenditure and physical activity. Data on energy and
      nutrient intake adequacy among elderly is important for disease prevention,
      health maintenance and program development. METHODS: This descriptive cross
      sectional study was designed to determine the energy requirements and adequacy of
      energy and nutrient intakes of older persons living in private households in a
      rural Filipino community. Study participants were generally-healthy, ambulatory,
      and community living elderly aged 60-100 y (n = 98), 88 of whom provided dietary
      information in three nonconsecutive 24-hour food-recall interviews. RESULTS:
      There was a decrease in both physical activity and food intake with increasing
      years. Based on total energy expenditure and controlling for age, gender and
      socio-economic status, the average energy requirement for near-old (>or= 60 to <
      65 y) males was 2074 kcal/d, with lower requirements, 1919 and 1699 kcal/d for
      the young-old (>or= 65 to < 75 y) and the old-old (>or= 75 y), respectively.
      Among females, the average energy requirements for the 3 age categories were
      1712, 1662, and 1398 kcal/d, respectively. Actual energy intakes, however, were
      only approximately 65% adequate for all subjects as compared to energy
      expenditure. Protein, fat, and micronutrients (vitamins A and C, thiamin,
      riboflavin, iron and calcium) intakes were only approximately 24-51% of the
      recommended daily intake. Among this population, there was a weight decrease of
      100 g (p = 0.012) and a BMI decrease of 0.04 kg/m2 (p = 0.003) for every 1%
      decrease in total caloric intake as percentage of the total energy expenditure
      requirements. CONCLUSION: These community living elderly suffer from lack of both
      macronutrient intake as compared with energy requirements, and micronutrient
      intake as compared with the standard dietary recommendations. Their energy
      intakes are ~65% of the amounts required based on their total energy expenditure.
      Though their intakes decrease with increasing age, so do their energy
      expenditure, making their relative insufficiency of food intake stable with age.

PMID- 19409111
TI  - ChlamyCyc: an integrative systems biology database and web-portal for
      Chlamydomonas reinhardtii.
AB  - BACKGROUND: The unicellular green alga Chlamydomonas reinhardtii is an important
      eukaryotic model organism for the study of photosynthesis and plant growth. In
      the era of modern high-throughput technologies there is an imperative need to
      integrate large-scale data sets from high-throughput experimental techniques
      using computational methods and database resources to provide comprehensive
      information about the molecular and cellular organization of a single organism.
      RESULTS: In the framework of the German Systems Biology initiative GoFORSYS, a
      pathway database and web-portal for Chlamydomonas (ChlamyCyc) was established,
      which currently features about 250 metabolic pathways with associated genes,
      enzymes, and compound information. ChlamyCyc was assembled using an integrative
      approach combining the recently published genome sequence, bioinformatics
      methods, and experimental data from metabolomics and proteomics experiments. We
      analyzed and integrated a combination of primary and secondary database
      resources, such as existing genome annotations from JGI, EST collections,
      orthology information, and MapMan classification. CONCLUSION: ChlamyCyc provides
      a curated and integrated systems biology repository that will enable and assist
      in systematic studies of fundamental cellular processes in Chlamydomonas. The
      ChlamyCyc database and web-portal is freely available under
      http://chlamycyc.mpimp-golm.mpg.de.

PMID- 19409112
TI  - The frequency of adverse drug reaction related admissions according to method of
      detection, admission urgency and medical department specialty.
AB  - BACKGROUND: Adverse Drug Reactions (ADRs) have been regarded as a major public
      health problem since they represent a sizable percentage of admissions.
      Unfortunately, there is a wide variation of ADR related admissions among
      different studies. The aim of this study was to evaluate the frequency of ADR
      related admissions and its dependency on reporting and method of detection,
      urgency of admissions and included medical departments reflecting
      department/hospital type within one study. METHODS: The study team of internal
      medicine specialists retrospectively reviewed 520 randomly selected medical
      records (3%) of patients treated in the medical departments of the primary city
      and tertiary referral governmental hospital for certain ADRs causing admissions
      regarding WHO causality criteria. All medical records were checked for whether
      the treating physicians recognised and documented ADRs causing admissions. The
      hospital information system was checked to ensure ADR related diagnoses were
      properly coded and the database of a national spontaneous reporting system was
      searched for patients with ADRs included in this study. RESULTS: The established
      frequency of admissions due to certain ADRs recognised by the study team and
      documented in medical records by the treating physicians was the same and
      represented 5.8% of all patients (30/520). The frequency of ADR causing
      admissions detected by employing a computer-assisted approach using an ICD-10
      coding system was 0.2% (1/520), and no patient admitted due to ADRs was reported
      to the national reporting system (0/520). The recognized frequency of ADR related
      admissions also depends on the department's specialty (p = 0.001) and acceptance
      of urgently admitted patients (p = 0.001). Patients admitted due to ADRs were
      significantly older compared to patients without ADRs (p = 0.025).
      Gastrointestinal bleeding due to NSAID, acetylsalicylic acid and warfarin was the
      most common ADR that resulted in admission and represented 40% of all certain
      ADRs (12/30) according to WHO causality criteria. CONCLUSION: ADRs cause 5.8% of
      admissions in medical departments in the primary city and tertiary referral
      hospital. The physicians recognise certain ADR related admissions according to
      WHO causality criteria and note them in medical records, but they rarely code and
      report ADRs. The established frequency of ADR related admissions depends on the
      detection method, department specialty and frequency of urgently admitted
      patients.

PMID- 19409113
TI  - Luteinizing hormone induces expression of 11beta-hydroxysteroid dehydrogenase
      type 2 in rat Leydig cells.
AB  - BACKGROUND: Leydig cells are the primary source of testosterone in male
      vertebrates. The biosynthesis of testosterone in Leydig cells is strictly
      dependent on luteinizing hormone (LH). On the other hand, it can be directly
      inhibited by excessive glucocorticoid (Corticosterone, CORT, in rats) which is
      beyond the protective capability of 11beta-Hydroxysteroid dehydrogenase type 1
      (11beta-HSD1) and type 2 (11beta-HSD2; encoded by gene Hsd11b2 in rats) in Leydig
      cells. Our previous study found that LH increases 11beta-HSD1 expression in rat
      Leydig cells, but the effect of LH on the expression and activity of 11beta-HSD2
      is not investigated yet. METHODS: The Leydig cells were isolated from male
      Sprague-Dawley rats (90 days of age). After Leydig cells were incubated either
      for 24 h with various concentrations of LH (2.5, 5, 10 and 20 ng/mL) or for
      different time periods (2, 8, 12 and 24 h) with 20 ng/mL LH, the mRNA expression
      of 11beta-HSD2 was measured by real-time PCR. 11beta-HSD2 protein levels in
      Leydig cells were assayed by Western Blot and 11beta-HSD2 enzyme activity was
      determined by calculating the ratio of conversion of [3H]CORT to [3H]11
      dehydrocorticosterone by 24 h after stimulation with 20 ng/ml LH. Four reporter
      gene plasmids containing various lengths of Hsd11b2 promoter region were
      constructed and transfected into mouse Leydig tumor cells to investigate the
      effect of LH on Hsd11b2 transcription. A glucocorticoid-responsive reporter gene
      plasmid, GRE-Luc, was constructed. To evaluate influence of LH on intracellular
      glucocorticoid level, rat Leydig cells were transfected with GRE-Luc, and
      luciferase activities were measured after incubation with CORT alone or CORT plus
      LH. RESULTS: We observed dose- and temporal-dependent induction of rat 11beta
      HSD2 mRNA expression in Leydig cells subject to LH stimulation. The protein and
      enzyme activity of 11beta-HSD2 and the luciferase activity of reporter gene
      driven by promoter regions of Hsd11b2 were increased by LH treatment. LH
      decreased the glucocorticoid-induced luciferase activity of GRE-Luc reporter
      gene. CONCLUSION: The results of the present study suggest that LH increases the
      expression and enzyme activity of 11beta-HSD2, and therefore enhances capacity
      for oxidative inactivation of glucocorticoid in rat Leydig cells in vitro.

PMID- 19409116
TI  - Laparoscopic radical prostatectomy: a review.
AB  - INTRODUCTION: We offer an overview of the intra-, peri- and postoperative
      outcomes of laparoscopic radical prostatectomy (LRP) with the endpoint to
      evaluate potential advantages of this approach. MATERIALS AND METHODS: We
      conducted an extensive Medline literature search (search terms "laparoscopic
      radical prostatectomy" and "radical prostatectomy") from 1990 until 2007. Only
      full-length English language articles identified during this search were
      considered for this analysis. A preference was given to the articles with large
      series with more than 100 patients. All pertinent articles concerning localized
      prostate cancer were reviewed. CONCLUSION: Pure LRP has shown to be feasible and
      reproducible but it is difficult to learn. Potential advantages over open surgery
      have to be confirmed by longer-term follow-up and adequately designed clinical
      studies.

PMID- 19409114
TI  - Short term exposure to cooking fumes and pulmonary function.
AB  - BACKGROUND: Exposure to cooking fumes may have different deleterious effects on
      the respiratory system. The aim of this study was to look at possible effects
      from inhalation of cooking fumes on pulmonary function. METHODS: Two groups of 12
      healthy volunteers (A and B) stayed in a model kitchen for two and four hours
      respectively, and were monitored with spirometry four times during twenty four
      hours, on one occasion without any exposure, and on another with exposure to
      controlled levels of cooking fumes. RESULTS: The change in spirometric values
      during the day with exposure to cooking fumes, were not statistically
      significantly different from the changes during the day without exposure, with
      the exception of forced expiratory time (FET). The change in FET from entering
      the kitchen until six hours later, was significantly prolonged between the
      exposed and the unexposed day with a 15.7% increase on the exposed day, compared
      to a 3.2% decrease during the unexposed day (p-value = 0.03). The same tendency
      could be seen for FET measurements done immediately after the exposure and on the
      next morning, but this was not statistically significant. CONCLUSION: In our
      experimental setting, there seems to be minor short term spirometric effects,
      mainly affecting FET, from short term exposure to cooking fumes.

PMID- 19409117
TI  - Can infundibular height predict the clearance of lower pole calyceal stone after
      extracorporeal shockwave lithotripsy?
AB  - PURPOSE: To evaluate the efficacy of extracorporeal shock wave lithotripsy (SWL)
      on lower calyceal calculi in relation to the renal anatomical factors and
      determine which of these factors can be used to select patients who will benefit
      from SWL. MATERIALS AND METHODS: We analyzed retrospectively 78 patients with
      single radiopaque lower calyceal stones treated with SWL. The patients were
      evaluated 3 months after lithotripsy with a simple abdominal X-ray and a kidney
      ultrasound scan. The success of the treatment, removal of all fragments, was
      correlated with renal anatomical factors measured in the pre-treatment
      intravenous urography: infundibulopelvic angle, lower infundibulum width, lower
      infundibulum length, ratio length/width, infundibulum height, and number of minor
      calyces in the lower calyceal group. RESULTS: Three months after SWL treatment,
      39 patients were stone-free (NR group) and 39 had residual fragments (R group).
      Both groups presented no differences in relation to infundibulopelvic angle,
      width and length of the lower calyceal infundibulum, length/width ratio of the
      lower infundibulum or number of lower calyces. Height of the infundibulum,
      described as the distance between the line passing through the lowest part of the
      calyx containing the calculus and the highest point of the lower lip of renal
      pelvis, was the only parameter in which significant differences (p = 0.002) were
      found between the NR and R groups. CONCLUSIONS: Lower Infundibular height could
      be a good measurement tool for deciding which patients with lower calyceal
      lithiasis would benefit from SWL treatment. Height of less than 22 mm suggests a
      good outcome from lithotripsy.

PMID- 19409118
TI  - Perioperative outcomes of open radical prostatectomy versus laparoscopic radical
      prostatectomy in Asian men: comparison of two initial series by the same surgeon.
AB  - PURPOSE: To compare the perioperative outcomes in 2 initial series of open
      radical prostatectomy (ORP) and laparoscopic radical prostatectomy (LRP) in Asian
      men with prostate cancer. MATERIALS AND METHODS: From March 1999 to February
      2007, the first 100 consecutive patients who underwent ORP and the first 100
      consecutive patients who underwent LRP by the same surgeon (SL) were assessed.
      Mean age, clinical stage, preoperative PSA level, Gleason score, operative time,
      estimated blood loss, blood transfusion rate, perioperative complications,
      pathological stage and margin status were compared between the 2 groups. RESULTS:
      For each 100 patients in ORP and LRP, mean age and clinical stage were not
      significantly different. The operative time in LRP was significantly longer than
      ORP (188 +/- 55 versus 114 +/- 31 minute, p value = 0.01). Mean estimated blood
      loss and blood transfusion rate in LRP was significantly lower than ORP, 521 +/-
      328 versus 809 +/- 510 mL (p value = 0.03) and 27% versus 55% (p value = 0.01),
      respectively. For pathological organ confined disease, the free surgical margin
      rate of ORP and LRP was not significantly different (88.9% versus 91.3%,
      respectively, p = 0.58). There was no significant major complication in either
      group. CONCLUSIONS: For initial experience by a single surgeon, LRP is comparable
      to ORP with no significant morbidity. LRP had longer operative time. However, LRP
      decreased blood loss and blood transfusion. For localized prostate cancer, free
      surgical margin rate of ORP and LRP was not significantly different.

PMID- 19409119
TI  - Reducing the number of sutures for vesicourethral anastomosis in radical
      retropubic prostatectomy.
AB  - OBJECTIVES: To prospectively evaluate the outcome of using a two-suture technique
      for the vesicourethral anastomosis (VUA) during radical retropubic prostatectomy
      (RRP). MATERIALS AND METHODS: Two groups of 50 patients each underwent nerve
      sparing RRP for localized prostate cancer by one surgeon. In one group, the
      vesicourethral anastomosis was performed using 2 Vicryl 2-0 stitches placed at
      the 3- and 9-o'clock positions and in the other group 6 Vicryl 2-0 stitches were
      placed at the 2-, 4-, 6-, 8-, 10- and 12-o'clock positions. The intraoperative
      and perioperative parameters analyzed were time to perform the VUA, time to
      remove the drain and hospitalization. The rate of incontinence, anastomotic
      stricture and erectile function were included in the outcome analysis. RESULTS:
      The anastomotic time differed statistically between the 2 groups (mean 3.3
      minutes for the 2-suture group and 10.5 minutes for the 6-suture group, p <
      0.0001) with similar periods of drain removal (mean 3.12 days for the 2-suture
      group and 3.45 days for the 6-suture group; p = 0.13) and hospitalization (mean
      4.66 days for the 2-suture group and 5.3 days for the 6-suture group; p = 0.09).
      The functional outcome was excellent for the 2-suture group with no patient
      suffering from incontinence or anastomotic strictures 1 year postoperatively,
      while in the 6-suture group there were 2 patients (4%) suffering from
      incontinence (2 underwent sling procedure) and 1 patient suffered from
      anastomotic stricture. CONCLUSION: The low number of sutures in the 2-suture VUA
      technique reduces operating times, does not influence perioperative and
      intraoperative parameters and results in excellent functional outcome.

PMID- 19409120
TI  - Uni- vs. multiloculated pelvic lymphoceles: differences in the treatment of
      symptomatic pelvic lymphoceles after open radical retropubic prostatectomy.
AB  - PURPOSE: To evaluate the treatment of symptomatic pelvic lymphoceles (SPL) after
      performing radical retropubic prostatectomy (RRP) and pelvic lymphadenectomy
      (PLA) simultaneously. MATERIAL AND METHODS: We analyzed, in a retrospective
      study, 250 patients who underwent RRP with PLA simultaneously. Only patients with
      SPL were treated using different non- and invasive procedures such as
      percutaneous aspiration, percutaneous catheter drainage (PCD) with or without
      sclerotherapy, laparoscopic lymphocelectomy (LL) and open marsupialization (OM).
      RESULTS: Fifty-two patients (21%) had postoperative subclinical pelvic
      lymphoceles. Thirty patients (12%) developed SPL. Fifteen patients with
      noninfected uniloculated lymphocele (NUL) healed spontaneously after performing
      PCD. The remaining seven patients required sclerotherapy with additional
      doxycycline. After performing PCD, NUL healed better and faster than noninfected
      multiloculated lymphocele (NML) (success rate: 80% vs. 16%, respectively). Twenty
      seven percent of patients treated initially with PCD, with or without
      sclerotherapy had persistent lymphocele. All patients were successfully treated
      with LL. Only one patient had an abscess as a major complication of a persistent
      SPL after PCD and sclerotherapy and was treated via an open laparotomy.
      CONCLUSIONS: Symptomatic NUL can be treated using PCD with or without
      sclerotherapy. If this therapy fails as first-line treatment, laparoscopic
      lymphocelectomy should be considered within a short period of time in order to
      achieve successful treatment. NML should be treated using a laparoscopic approach
      in centers where this type of expertise is available. Infected lymphoceles are
      drained externally. In these cases, percutaneous or open external drainage with
      adequate antibiotic coverage is preferable.

PMID- 19409122
TI  - Risk factors for bone loss with prostate cancer in Korean men not receiving
      androgen deprivation therapy.
AB  - PURPOSE: Preexisting bone loss in men with prostate cancer is an important issue
      due to the accelerated bone loss during androgen deprivation therapy (ADT). In
      addition, a high prostate-specific antigen (PSA) level has been reported to be
      related to bone metabolism. This study assessed the factors associated with
      osteoporosis in Korean men with non-metastatic prostate cancer before undergoing
      ADT. MATERIALS AND METHODS: The study enrolled patients admitted for a prostate
      biopsy because of a high PSA or palpable nodule on a digital rectal examination.
      We divided the patients (n = 172) according to the results of the biopsy: group
      I, non-metastatic prostate cancer (n = 42) and group II, benign prostatic
      hypertrophy (BPH; n = 130). The lumbar bone mineral density (BMD) was evaluated
      using quantitative computed tomography. The demographic, health status,
      lifestyle, body mass index (BMI), serum testosterone concentration, and disease
      variables in prostate cancer (Gleason score, clinical stage, and PSA) were
      analyzed prospectively to determine their effect on the BMD. RESULTS: The
      estimated mean T-score was higher in group I than in group II (-1.96 +/- 3.35 vs.
      -2.66 +/- 3.20), but without statistic significance (p = 0.235). The significant
      factors correlated with BMD in group I were a high serum PSA (Beta = -0.346, p =
      0.010) and low BMI (Beta = 0.345, p = 0.014) in the multiple linear regression
      model. Also old age (r = -0.481, p = 0.001), a high serum PSA (r = -0.571, p <
      0.001), low BMI (r = 0.598, p < 0.001), and a high Gleason's score (r = -0.319, p
      = 0.040) were the factors related to BMD in the correlation. The significant
      factors correlated with BMD in group II were old age (Beta = -0.324, p = 0.001)
      and BMI (Beta = 0.143, p = 0.014) in the multiple linear regression model.
      CONCLUSIONS: The risk factors for osteoporosis in men with prostate cancer
      include a low BMI, and elevated serum PSA. Monitoring BMD from the outset of ADT
      is a logical first step in the clinical strategy to avoid or minimize potential
      bone-related complications in these patients.

PMID- 19409123
TI  - Sperm banking for male cancer patients: social and semen profiles.
AB  - PURPOSE: Report the characteristics of cryopreserved semen from a cohort of male
      cancer patients, attitudes towards cryopreservation and outcomes of semen samples
      based on a 12-year cryopreservation program. MATERIAL AND METHODS: Data from 98
      male cancer patients whose sperm samples were banked were evaluated. Demographic
      parameters, semen characteristics, destination of sperm banked samples and
      questionnaires answered by the patients regarding cryopreservation time were
      evaluated. RESULTS: The cancer diagnoses were testicle (56.1%), prostate (15.3%),
      Hodgkin's lymphomas (9.2%), non-Hodgkin's lymphomas (7.1%), leukemia (3.1%) and
      other malignancies (9.2%). The patients with testicular cancer presented lower
      sperm concentration (p < 0.001); however, there were no differences with the
      percentage of normozoospermic patients among cancer type groups (p = 0.185). A
      shorter time between cancer diagnosis and sperm banking was observed for
      testicular and prostate cancer patients (p < 0.001). Most of the patients (89.5%)
      favored sperm banking as a fertility preservation method. CONCLUSIONS: Although
      less than 20% of banked sperm samples were disposed of, the majority of patients
      related sperm banking with safe for fertility preservation. Our results show that
      all male cancer patients of reproductive age facing cancer treatment could be
      offered sperm banking.

PMID- 19409124
TI  - Robotic-assisted partial nephrectomy: surgical technique using a 3-arm approach
      and sliding-clip renorrhaphy.
AB  - INTRODUCTION: For the treatment of renal tumors, minimally invasive nephron
      sparing surgery has become increasingly performed due to proven efficiency and
      excellent functional and oncological outcomes. The introduction of robotics into
      urologic laparoscopic surgery has allowed surgeons to perform challenging
      procedures in a reliable and reproducible manner. We present our surgical
      technique for robotic assisted partial nephrectomy (RPN) using a 3-arm approach,
      including a sliding-clip renorrhaphy. MATERIALS AND METHODS: Our RPN technique is
      presented which describes the trocar positioning, hilar dissection, tumor
      identification using intraoperative ultrasound for margin determination,
      selective vascular clamping, tumor resection, and reconstruction using a sliding
      clip technique. CONCLUSION: RPN using a sliding-clip renorrhaphy is a valid and
      reproducible surgical technique that reduces the challenge of the procedure by
      taking advantage of the enhanced visualization and control afforded by the robot.
      The renorrhaphy described is performed under complete control of the console
      surgeon, and has demonstrated a reduction in the warm ischemia times in our
      series.

PMID- 19409125
TI  - A new extra-abdominal channel alternative to the Mitrofanoff principle:
      experimental and preliminary clinical experience.
AB  - INTRODUCTION: The appendix is the gold-standard channel for the Mitrofanoff
      principle in pediatric urology, but the search for alternatives is justified
      considering it may not be available or preferably used for colonic stomas (Malone
      antegrade continence enema). The aim of this study is to report on technical
      feasibility of a new approach for creating catheterizable channels in a rabbit
      model and to present our preliminary clinical experience. MATERIAL AND METHODS:
      We configured a tube from two rectangular skin flaps 1x4 cm opposite each other
      in the middle line of the lower inferior abdomen. The channel was anastomosed to
      the bladder dome with embedding sutures to create a valvular mechanism. The
      experimental study consisted of 12 rabbits, divided in 4 groups according to the
      sacrifice schedule at 2, 4, 8 and 12 weeks. At 30th postoperative day, an
      urodynamic evaluation was performed to record continence of the stoma. A
      histological analysis of the specimens stained with hematoxylin-eosin, Masson
      trichrome and Picrosirius red was also done in group 2 (sacrifice at 4 weeks
      postoperatively). We used this method in 3 patients with congenital non
      neurogenic bladder disease presenting with massive residual volumes without
      compliance deficits. RESULT: The technique proved feasible in all animals, 9 of
      12 could be easily catheterized and underwent urodynamic study. No stoma leakage
      was observed in 7 animals at high bladder pressures (> 50 cm H20) and only 2
      animals had some leakage at 40 cm H20. Urodynamics performed through the stoma
      showed urethral leakage at 20 cm H20, therefore demonstrating the efficacy of the
      valvular mechanism. Histological analysis confirmed good integration between the
      tube and the bladder. Mean follow-up of the clinical series (3 patients) was 7.2
      months. Two patients remained continent up to 4 hours, whereas 1 patient had some
      leakage after 2 hours. CONCLUSION: We were able to confirm feasibility of a new
      extra-abdominal channel based on the Mitrofanoff principle and successfully
      reproduced the method in a clinical setting. Follow-up was short and long term
      results are required before any conclusive judgment can be made.

PMID- 19409121
TI  - T2-Weighted endorectal magnetic resonance imaging of prostate cancer after
      external beam radiation therapy.
AB  - PURPOSE: To retrospectively determine the accuracy of T2-weighted endorectal MR
      imaging in the detection of prostate cancer after external beam radiation therapy
      and to investigate the relationship between imaging accuracy and time since
      therapy. MATERIALS AND METHODS: Institutional review board approval was obtained
      and the study was HIPPA compliant. We identified 59 patients who underwent 1.5
      Tesla endorectal MR imaging of the prostate between 1999 and 2006 after
      definitive external beam radiation therapy for biopsy-proven prostate cancer. Two
      readers recorded the presence or absence of tumor on T2-weighted images. Logistic
      regression and Fisher's exact tests for 2x2 tables were used to determine the
      accuracy of imaging and investigate if accuracy differed between those imaged
      within 3 years of therapy (n = 25) and those imaged more than 3 years after
      therapy (n = 34). Transrectal biopsy was used as the standard of reference for
      the presence or absence of recurrent cancer. RESULTS: Thirty-four of 59 patients
      (58%) had recurrent prostate cancer detected on biopsy. The overall accuracy of
      T2-weighted MR imaging in the detection cancer after external beam radiation
      therapy was 63% (37/59) for reader 1 and 71% for reader 2 (42/59). For both
      readers, logistic regression showed no difference in accuracy between those
      imaged within 3 years of therapy and those imaged more than 3 years after therapy
      (p = 0.86 for reader 1 and 0.44 for reader 2). CONCLUSION: T2-weighted endorectal
      MR imaging has low accuracy in the detection of prostate cancer after external
      beam radiation therapy, irrespective of the time since therapy.

PMID- 19409126
TI  - Use of a latex biomembrane for bladder augmentation in a rabbit model:
      biocompatibility, clinical and histological outcomes.
AB  - PURPOSE: To investigate histological features and biocompatibility of a latex
      biomembrane for bladder augmentation using a rabbit model. MATERIAL AND METHODS:
      After a partial cystectomy, a patch of a non-vulcanized latex biomembrane (2x4
      cm) was sewn to the bladder with 5/0 monofilament polydioxanone sulfate in a
      watertight manner. Groups of 5 animals were sacrificed at 15, 45 and 90 days
      after surgery and the bladder was removed. The 5-mum preparations obtained from
      grafted area and normal bladder were stained with hematoxylin-eosin.
      Immunohistochemical staining was performed with a primary antibody against alpha
      actin to assess muscle regeneration. RESULTS: No death, urinary leakage or graft
      extrusion occurred in any group. All bladders showed a spherical shape.
      Macroscopically, after 90 days, the latex biomembrane was not identifiable and
      the patch was indistinguishable from normal bladder. A bladder stone was found in
      one animal (6.6%). On the 90th day, histology revealed continuity of transitional
      epithelium of host bladder tissue on the patch area. At this time, the muscle
      layers were well organized in a similar fashion to native bladder muscle layers.
      The inflammatory process was higher on grafted areas when compared to controls:
      15 days--p < 0.0001, 45 days--p < 0.001, and 90 days--p < 0.01. The anti alpha
      actin immunoexpression peaked at 45 days, when the graft was observed covered by
      muscle cells. CONCLUSION: The latex biomembrane is biocompatible and can be used
      in models for bladder augmentation in rabbits. It promotes epithelium and muscle
      regeneration without urinary leakage.

PMID- 19409127
TI  - Re: In vitro evidence for a new therapeutic approach in renal cell carcinoma.

PMID- 19409144
TI  - Surgical management of Boerhaave's syndrome in a tertiary oesophagogastric
      centre.
AB  - INTRODUCTION: The aim of this study was to review the management and outcome of
      patients with Boerhaave's syndrome in a specialist centre between 2000-2007.
      PATIENTS AND METHODS: Patients were grouped according to time from symptoms to
      referral (early, < 24 h; late, > 24 h). The effects of referral time and
      management on outcomes (oesophageal leak, reoperation and mortality) were
      evaluated. RESULTS: Of 21 patients (early 10; late 11), three were unfit for
      surgery. Of the remaining 18, immediate surgery was performed in 8/8 referred
      early and 6/10 referred late. Four patients referred late were treated
      conservatively. Oesophageal leak (78% versus 12.5%; P < 0.05) and mortality (40%
      versus 0%; P < 0.05) rates were higher in patients referred late. For patients
      referred late, mortality was higher in patients managed conservatively (75%
      versus 17%; not significant). CONCLUSIONS: The best outcomes in Boerhaave's
      syndrome are associated with early referral and surgical management in a
      specialist centre. Surgery appears to be superior to conservative treatment for
      patients referred late.

PMID- 19409145
TI  - Meniscal allograft transplantation: a review of the current literature.
AB  - INTRODUCTION: Patients who have previously undergone meniscectomy are known to
      potentially suffer subsequent knee problems including degenerative changes.
      Meniscal transplantation has been proposed as a possible solution to these
      problems. This article aims to review the current literature to consolidate the
      evidence surrounding the use of human meniscal allograft transplantation.
      MATERIALS AND METHODS: Three databases (PubMed, Embase and Medline) were searched
      to find English language articles pertaining to meniscal allograft
      transplantation. Each article was critiqued by two authors using a structured
      appraisal tool, and stratified according to the level of evidence. RESULTS: No
      Level I or II studies were identified. Many studies had small study groups with
      limited follow-up and patient selection and description of patient factors varied
      greatly. This made comparing data difficult. There were also very few papers
      concentrating on isolated meniscal transplantation. Four types of graft are used-
      fresh, fresh-frozen, cryopreserved and freeze-dried (lyophilised) graft.
      Cryopreserved and fresh-frozen allografts are deemed most suitable. Most authors
      advocate the use of non-irradiated grafts from screened donors to reduce
      transmission of infection. Best results occur when using bony anchors to fix the
      graft, although this requires accurate graft positioning. Patients have an
      improved outcome if they have less severe degenerative changes within the knee
      prior to transplantation. CONCLUSIONS: No statistically significant studies
      looking at isolated meniscal transplantations have been found. The evidence
      suggests that meniscal allograft transplantation provides improvement of pain and
      function in the short and intermediate term. The effect on future joint
      degeneration is still unknown. The ideal patient group includes patients less
      than 40 years of age with knee pain, proven meniscal injury and a normally
      aligned, stable joint without severe degenerative changes.

PMID- 19409146
TI  - Ultrasensitive prostate specific antigen assay following laparoscopic radical
      prostatectomy--an outcome measure for defining the learning curve.
AB  - INTRODUCTION: Radical retropubic prostatectomy (RRP) performed laparoscopically
      is a popular treatment with curative intent for organ-confined prostate cancer.
      After surgery, prostate specific antigen (PSA) levels drop to low levels which
      can be measured with ultrasensitive assays. This has been described in the
      literature for open RRP but not for laparoscopic RRP. This paper describes PSA
      changes in the first 300 consecutive patients undergoing non-robotic laparoscopic
      RRP by a single surgeon. OBJECTIVES: To use ultrasensitive PSA (uPSA) assays to
      measure a PSA nadir in patients having laparoscopic radical prostatectomy below
      levels recorded by standard assays. The aim was to use uPSA nadir at 3 months'
      post-prostatectomy as an early surrogate end-point of oncological outcome. In so
      doing, laparoscopic oncological outcomes could then be compared with published
      results from other open radical prostatectomy series with similar end-points.
      Furthermore, this end-point could be used in the assessment of the surgeon's
      learning curve. PATIENTS AND METHODS: Prospective, comprehensive, demographic,
      clinical, biochemical and operative data were collected from all patients
      undergoing non-robotic laparoscopic RRP. We present data from the first 300
      consecutive patients undergoing laparoscopic RRP by a single surgeon. uPSA was
      measured every 3 months post surgery. RESULTS: Median follow-up was 29 months
      (minimum 3 months). The likelihood of reaching a uPSA of < or = 0.01 ng/ml at 3
      months is 73% for the first 100 patients. This is statistically lower when
      compared with 83% (P < 0.05) for the second 100 patients and 80% for the third
      100 patients (P < 0.05). Overall, 84% of patients with pT2 disease and 66%
      patients with pT3 disease had a uPSA of < or = 0.01 ng/ml at 3 months. Pre
      operative PSA, PSA density and Gleason score were not correlated with outcome as
      determined by a uPSA of < or = 0.01 ng/ml at 3 months. Positive margins correlate
      with outcome as determined by a uPSA of < or = 0.01 ng/ml at 3 months but
      operative time and tumour volume do not (P < 0.05). Attempt at nerve sparing had
      no adverse effect on achieving a uPSA of < or = 0.01 ng/ml at 3 months.
      CONCLUSIONS: uPSA can be used as an early end-point in the analysis of
      oncological outcomes after radical prostatectomy. It is one of many measures that
      can be used in calculating a surgeon's learning curve for laparoscopic radical
      prostatectomy and in bench-marking performance. With experience, a surgeon can
      achieve in excess of an 80% chance of obtaining a uPSA nadir of < or = 0.01 ng/ml
      at 3 months after laparoscopic RRP for a British population. This is equivalent
      to most published open series.

PMID- 19409147
TI  - Feeding patients following pancreaticoduodenectomy: a UK national survey.
AB  - INTRODUCTION: Providing nutrition for patients following pancreaticoduodenectomy
      (PD) is vital but can be challenging. Due to the lack of UK national guidelines
      for the provision of nutrition and nutritional pre-operative assessment regarding
      PD, a national survey was conducted. PATIENTS AND METHODS: A questionnaire was
      sent to the Department of Nutrition and Dietetics at each of the 31 specialist
      pancreatic centres listed with the Pancreatic Society of Great Britain and
      Ireland. Questions were asked regarding the nutritional assessment and treatment
      of patients undergoing classical PD and pylorus-preserving PD (PPPD) resections.
      RESULTS: Twenty-two centres responded to the questionnaire. With regard to PD and
      PPPD, 82% routinely feed patients following resection, 32% have a regimen for
      staring feeds, 18% carry out pre-operative nutritional assessment, five centres
      have funding for an hepatobiliary dietition, and only four centres have a
      specialist hepatobiliary dietition employed. There was no consensus regarding the
      type or route of feeding, and at least one centre reported using parenteral
      nutrition exclusively. CONCLUSIONS: Very few centres in the UK have funding for a
      hepatobiliary dietition. Hence pre-operative nutritional assessment in patients
      undergoing PD and PPPD does not receive much input. Although the importance of
      postoperative feeding in these patients is appreciated in all major units, there
      is no consensus with regards to feeding regimens. The authors hope this
      observational study will address these issues with this important message and
      stimulate further study in this area.

PMID- 19409148
TI  - Correlation between rotator cuff tears and repeated subacromial steroid
      injections: a case-controlled study.
AB  - INTRODUCTION: Concern exists regarding potential damage to the rotator cuff from
      repeated corticosteroid injections into the subacromial space. PATIENTS AND
      METHODS: In this retrospective, case-controlled study, 230 consecutive patients
      presenting to three orthopaedic units with subacromial impingement and
      investigated as an end-point with magnetic resonance imaging (MRI) of the
      shoulder were divided into groups having received less than three or three or
      more subacromial injections of corticosteroids. RESULTS: With no significant
      difference in age and sex distribution, analysis by MRI showed no significant
      difference between the two groups in the incidence of rotator cuff tear (P <
      1.0). CONCLUSIONS: This suggests that corticosteroid use in patients with
      subacromial impingement should not be considered a causative factor in rotator
      cuff tears.

PMID- 19409149
TI  - A prospective audit of endoscopic vein harvesting for coronary artery bypass
      surgery.
AB  - INTRODUCTION: The objectives of this study were to: (i) assess the feasibility of
      minimally invasive endoscopic harvesting of the long saphenous vein or radial
      artery for use as conduit during coronary artery bypass surgery in the NHS
      setting; and (ii) investigate the results of endoscopic vein harvesting with
      regards to postoperative complications, ability to mobilise, and patient
      satisfaction. PATIENTS AND METHODS: In this prospective audit, 25 consecutive
      patients, aged 52-90 years, undergoing either coronary artery bypass grafting
      alone or together with valve surgery or atrial fibrillation ablation were
      studied. All data were entered in purpose-designed proforma. Pre-operative risk
      factors including increasing age, diabetes, peripheral vascular disease, obesity,
      renal impairment, tobacco consumption and steroid use were documented. Time taken
      for harvest and conversion to traditional open vein harvest, quality of harvested
      vein in terms of number of repairs and vein damage were recorded.
      Postoperatively, we recorded harvest site wound complications, number of days to
      mobilise and total hospital stay. Pain score and patient satisfaction were also
      assessed. RESULTS: There was one death due to myocardial infarction; another
      patient had postoperative cerebrovascular accident. A total of 43 lengths of
      grafts were harvested, 41 were long saphenous vein and two radial artery. Vein
      harvest time reduced significantly from a maximum of 94 min to 34 min for two
      lengths of long saphenous vein. Three patients required conversion from
      endoscopic vein harvesting to open vein harvest. The only postoperative
      complication directly related to endoscopic harvesting was bruising along the
      tunnel created by the passage of the instruments. None of the patients had any
      wound complication; none required antibiotics or wound debridement. Mean time to
      mobilise was 3.4 days. All patients who underwent successful endoscopic vein
      harvesting expressed satisfaction with regards to postoperative pain and cosmetic
      result. CONCLUSIONS: Competence and ability to harvest conduit in an acceptable
      time frame are obtainable after a relatively low number of cases. The procedure
      is associated with a low number of postoperative complications and very high
      patient satisfaction.

PMID- 19409150
TI  - The EndoAssist robotic camera holder as an aid to the introduction of
      laparoscopic colorectal surgery.
AB  - INTRODUCTION: Introducing laparoscopic colorectal surgery is a challenge to the
      whole surgical team. It is usual for an assistant to hold the laparoscope and be
      responsible for the surgeon's view of the operative field and a lack of expertise
      in the assistant can add significant difficulties. The EndoAssist is a robotic
      device that replaces the human assistant and ensures steady visualisation of the
      operative field and a view which can be controlled by the surgeon. This study
      describes its use in the introduction of laparoscopic colorectal surgery to a
      unit. PATIENTS AND METHODS: The EndoAssist was employed for the introduction of
      laparoscopic colorectal surgery in a unit with previous experience of this device
      for laparoscopic cholecystectomy. It was used in a consecutive series of 77
      laparoscopic colectomy operations. RESULTS: The robotic device proved successful
      in the whole range of colorectal operations and a reliable assistant. No problems
      specific to the device were encountered. CONCLUSIONS: The EndoAssist robot is a
      useful laparoscopic assistant and aided in the introduction of laparoscopic
      colorectal surgery.

PMID- 19409153
TI  - A second national survey of health-related quality of life questionnaires in head
      and neck oncology.
AB  - INTRODUCTION: With an increasing number of publications on health-related quality
      of life (HRQOL) following head and neck cancer, the recognition of a number of
      well-validated questionnaires and a growing awareness of the potential role of
      HRQOL in practice, it was our aim to repeat the survey of 2002 reported in the
      Annals to see how practice changed. MATERIALS AND METHODS: A postal survey of
      members of the British Association of Head and Neck Oncologists was undertaken in
      January 2006 with reminders sent in February, March and April. RESULTS: The
      response was 50% (106 of 210) of which 53% were using or had used HRQOL
      questionnaires. The main reasons for not using HRQOL questionnaires were that
      they were too time-consuming or intrusive in a clinic setting and that there was
      a lack of resources. CONCLUSIONS: Clinicians still see the use of questionnaires
      as a research-tool only, rather than an adjunct to giving patient information,
      promoting choice, and identifying patients with problems. The burden on HRQOL
      evaluation in routine clinical practice remains a substantial barrier. Advances
      with IT support in clinic should make it easier to collect and use these data in
      the future. As surgeons, we still need to be persuaded of the benefits of HRQOL
      outcomes in our practice.

PMID- 19409152
TI  - The role of routine assays of serum amylase and lipase for the diagnosis of acute
      abdominal pain.
AB  - INTRODUCTION: We aimed to evaluate the role of routine measurements of serum
      amylase and lipase in the diagnosis of acute abdominal pain. PATIENTS AND
      METHODS: We identified all patients who had serum amylase and lipase assays over
      a 62-day period at a single university teaching hospital and reviewed their case
      notes. RESULTS: We excluded 58 of the 1598 patients on grounds of ineligibility
      (< 18 years of age and those transferred from other hospitals). A complete data
      set was obtained for 1520 (98.7%) of the remaining 1540 patients. Only 9.1% of
      requests were based on a clinical suspicion of acute pancreatitis. Of the 44
      (2.9%) patients who had acute pancreatitis, only 28 (63.6%) had an associated
      rise in serum amylase and/or lipase 3 times above the maximum reference range,
      the remainder being diagnosed radiologically. At this cut-off range, the
      sensitivity and specificity for serum amylase were 50% and 99%, and those for
      serum lipase 64% and 97%, respectively. CONCLUSIONS: Routine measurements of
      serum amylase and lipase are unhelpful in the diagnosis of acute abdominal pain
      unless there is clinical suspicion of acute pancreatitis. In these patients,
      assay of lipase alone is preferable to assay of amylase alone or both enzymes.

PMID- 19409154
TI  - Enhanced external counterpulsation for the treatment of stable angina and heart
      failure: a systematic review and economic analysis.
AB  - OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of
      enhanced external counterpulsation (EECP) compared with usual care and placebo
      for refractory stable angina and heart failure, and to undertake analyses of the
      expected value of information to assess the potential value of future research on
      EECP. DATA SOURCES: Major electronic databases were searched between November
      2007 and March 2008. REVIEW METHODS: A systematic review of the literature was
      undertaken and a decision model developed to compare EECP treatment with no
      treatment in adults with chronic stable angina. RESULTS: Five studies were
      included in the review. In the Multicenter Study of Enhanced External
      Counterpulsation (MUST-EECP), time to greater than or equal to 1-mm ST segment
      depression (exercise-induced ischaemia) was statistically significantly improved
      in the EECP group compared with the control group (sham EECP), mean difference
      (MD) 41 seconds [95% confidence interval (CI) 9.10-73.90]. However, there was no
      statistically significant difference between the EECP and control groups in the
      change in exercise duration from baseline to end of treatment, self-reported
      angina episodes or daily nitroglycerin use, and the clinical significance of the
      limited benefits was unclear. There was also a lack of data on long-term
      outcomes. There were more withdrawals due to adverse events in the EECP group
      than in the control group, as well as a greater proportion of patients with
      adverse events [relative risk (RR) 2.13, 95% CI 1.35-3.38]. The three non
      randomised studies compared EECP with elective percutaneous coronary intervention
      (PCI) and usual care. There was a high risk of selection bias in all three
      studies and the results should be treated with considerable caution. The study
      comparing an EECP registry with a PCI registry reported similar 1-year all-cause
      mortality in both groups. In the Prospective Evaluation of EECP in Congestive
      Heart Failure (PEECH) trial, patients with heart failure were randomised to EECP
      or to usual care (pharmacotherapy only). At 6 months post treatment, the
      proportion of patients achieving at least a 60-second increase in exercise
      duration was higher in the EECP group (RR 1.39, 95% CI 0.89-2.16), but the
      proportion with an improvement in peak VO2 was similar in both groups. The
      clinical significance of this is unclear. The proportion of patients in the EECP
      group with an improvement in New York Heart Association classification was higher
      (RR 2.25, 95% CI 1.25-4.06) at 6 months, as was mean exercise duration, MD 34.6
      (95% CI -4.86 to 74.06). There were more withdrawals in the EECP group than in
      the control group as a result of adverse events (RR 1.05, 95% CI 0.67-1.66).
      There were limitations in the generalisability of results of the trial and,
      again, a lack of data on long-term outcomes. The review of cost-effectiveness
      evidence found only one unpublished study but demonstrated that the long-term
      maintenance of quality of life benefits of EECP is central to the estimate of its
      cost-effectiveness. The incremental cost-effectiveness ratio of EECP was 18,643
      pounds for each additional quality-adjusted life-year (QALY), with a probability
      of being cost-effective of 0.44 and 0.70 at cost-effectiveness thresholds of
      20,000 pounds and 30,000 pounds per QALY gained respectively. Results were
      sensitive to the duration of health-related quality of life (HRQoL) benefits from
      treatment. CONCLUSIONS: The results from a single randomised controlled trial
      (MUST-EECP) do not provide firm evidence of the clinical effectiveness of EECP in
      refractory stable angina or in heart failure. High-quality studies are required
      to investigate the benefits of EECP, whether these outweigh the common adverse
      effects and its long-term cost-effectiveness in terms of quality of life
      benefits.

PMID- 19409155
TI  - Vitamin D deficiency in an ample sunlight country.

PMID- 19409151
TI  - Distal revascularisation with interval ligation (DRIL): an experience.
AB  - INTRODUCTION: The global increase of chronic renal failure has resulted in a
      growing number of patients on haemodialysis using arteriovenous fistulas (AVFs).
      By virtue of their very function, AVFs at times shunt blood away from regions
      distally, resulting in an ischaemic steal syndrome. Distal revascularisation with
      interval ligation (DRIL) has been described as a procedure to treat symptomatic
      ischaemic steal. We present our experience in the management of this
      complication. PATIENTS AND METHODS: Six patients with severe ischaemic steal were
      treated using a DRIL procedure between May 2004 and June 2007. There were three
      males and three females, all with elbow brachiocephalic AVFs. Symptoms ranged
      from severe rest pain to digital gangrene. Published results from international
      studies of 135 DRIL procedures were also reviewed. RESULTS: Vascular access was
      maintained along with the elimination of ischaemic symptoms in the six patients
      using an ipsilateral reversed basilic vein graft. Interval ligation of the distal
      brachial artery was performed at the same time. All patients showed immediate and
      sustained clinical improvement of symptoms with a demonstrable increase in
      digital pulse oximetry. CONCLUSIONS: DRIL is a beneficial treatment option that
      has proven successful at alleviating ischemic steal symptoms and preserving
      vascular access. This avoids placement of central lines, its associated risks,
      and the need to create an alternative sited fistula.

PMID- 19409156
TI  - High degree Atrioventricular block in patients with acute inferior Myocardial
      Infarction with and without Right Ventricular involvement.
AB  - OBJECTIVE: To determine the influence of time on development of high degree
      Atrioventricular (AV) block in patients with inferior Myocardial Infarction (MI),
      its association with Right Ventricular (RV) infarction and its ultimate morbidity
      and mortality. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY:
      The Emergency Department (ED) and the units of adult cardiology at National
      Institute of Cardiovascular Diseases (NICVD), Karachi, from October 2006 to March
      2007. METHODOLOGY: Patients presented at ED with typical chest pain and
      subsequently diagnosed by standardized diagnostic criteria as having inferior MI
      were recruited prospectively. Patients were first analyzed on the basis of
      absence (Group A) or presence (Group B) of high degree AV block regardless of RV
      infarction. Then after patients were divided into two groups, those without RV
      infarction (Group I) and with RV infarction (Group II). Each group was further
      sub-divided as Ia, IIa and Ib, IIb depending on absence or presence of high
      degree AV block respectively. Each group was analyzed for comparisons with
      different variables for prediction of influence of time, proportion of RV
      infarction, association of AV block with RV infarction, complication profile and
      inmortality. RESULTS: Of the 220 patients with inferior MI, 52 (23.6%) had high
      degree AV block and 83 (37.7%) had RV infarction. They were older in age (p<
      0.003). Patients who took more time to seek medical treatment from onset of
      symptoms were more prone to develop AV block (p<0.001). Among patients with
      block, 73% received thrombolytic therapy (p<0.009) and temporary pacemaker (TPM)
      was implanted in 75% (p<0.0001). Mortality was significantly high in those
      patients (p<0.0001). In group II, 61.4% presented with sinus rhythm (p<0.001).
      TPM was implanted to 31.3% (p<0.0001). In the 4 days of hospital course, 8.4% of
      patients with RV infarction developed AV block (p<0.005), whereas 10.8% of
      patients without RV infarction experienced post MI angina (p<0.031). Mortality
      was found significantly high when block was associated with RV infarction
      (p<0.007). No significant difference was found in response to atropine, volume
      replacement or streptokinase administration and reverting of block to sinus
      rhythm. CONCLUSION: Patients with inferior MI who took more time to seek medical
      treatment were found to be more prone to develop high degree AV block. RV
      infarction was found in about 38% of patients defined a high risk subgroup. High
      degree AV block significantly influenced the outcome when associated with RV
      infarction, leading to high mortality.

PMID- 19409157
TI  - Transcatheter closure of large sized patent ductus arteriosus using the amplatzer
      duct occluder device.
AB  - OBJECTIVE: To assess the results of anterograde transcatheter closure of a large
      sized patent ductus arteriosus using the Amplatzer Duct Occluder (ADO) device.
      STUDY DESIGN: A case series. PLACE AND DURATION OF STUDY: Department of
      Cardiology, Armed Forces Institute of Cardiology and National Institute of Heart
      Diseases, Rawalpindi, from January 2005 to December 2007. METHODOLOGY: All
      patients who underwent transcatheter closure of large sized PDA (> or = 4.0 mm),
      using the Amplatzer Duct Occluder (ADO) device, from January 2005 to December
      2007, were included by convenient sampling technique. After the procedure, repeat
      aortogram was performed to confirm the appropriate position of the ADO and to
      evaluate for residual shunts. RESULTS: A total of 100 patients had PDA diameter
      of > or = 4.00 mm. Mean age was 11.73 + 10.31 years and there were 37 males and
      63 females. Mean PDA diameter was 6.011 + 2.078 mm. Forty-nine patients had type
      'A', 19 had type 'B', 19 patients had type 'C', 5 had type 'D' and 8 patients had
      type 'E' PDA. Complete closure was achieved in 70 patients, 26 had trace shunt
      and 4 patients had small residual shunt immediately after the procedure. However,
      no patient had residual shunt 24 hours after the procedure. CONCLUSION: ADO is a
      highly efficient prosthesis that can be safely applied in most patients with PDA
      particularly in patients with large sized PDA.

PMID- 19409158
TI  - Factors associated with Non-Carious Cervical Lesions (NCCLs) in teeth.
AB  - OBJECTIVE: To determine factors associated with Non-Carious Cervical Lesions
      (NCCLs) and the teeth most commonly involved in such lesions. STUDY DESIGN: Cross
      sectional study. PLACE AND DURATION OF STUDY: Department of Operative Dentistry,
      Section of Dentistry at Aga Khan University Hospital, Karachi, Pakistan, from
      December 2005 to January 2006. METHODOLOGY: A total number of 95 patients with
      671 teeth were evaluated using a pre-coded questionnaire. Subject of evaluation
      was teeth. Patients with symptomatic or asymptomatic NCCLs and permanent
      dentition were included. Patients exhibiting active, untreatable periodontal
      disease, rampant uncontrolled caries, xerostomia, primary dentition, patients
      undergoing orthodontic treatment or bleaching procedure were excluded from the
      study. Data analysis was done using Spearman's correlation, Mann Whitney test and
      Kruskal-Wallis test. RESULTS: Mean age of patients was 50.3 years (r=0.22,
      p=0.028); males (73%) had more NCCLs than females (23%). Majority (45.3%) of them
      brushed their teeth twice a day, with medium type of brush (48.4%) and horizontal
      (73.7%) brushing technique. Most of the patients were non-bruxists (90.5%), with
      Angles Class 1 occlusion (48.4%) and canine guidance (50.5%). Majority (74.7%) of
      the patients did not have sensitivity. CONCLUSION: First premolars in all the
      quadrants were the most frequently involved teeth in NCCLs. More males had NCCLs.
      Middle aged patients were more involved. A weak positive correlation was found
      between age and NCCLs. No association was observed between hand used and site of
      NCCLs, between wear facets and NCCL, Excursive guidance and NCCL, Angles
      classification and NCCL.

PMID- 19409159
TI  - Propranolol, isosorbide mononitrate and endoscopic band ligation - alone or in
      varying combinations for the prevention of esophageal variceal rebleeding.
AB  - OBJECTIVE: To compare the efficacy of propranolol, propranolol with nitrate, band
      ligation, and band ligation with propranolol and nitrate for the prevention of
      esophageal variceal rebleeding. STUDY DESIGN: A prospective randomized trial.
      PLACE AND DURATION OF STUDY: Department of Gastroenterology and Hepatology,
      Sheikh Zayed Hospital, Lahore, from November 2003 to July 2005. METHODOLOGY: One
      hundred and sixty cirrhotic patients with esophageal variceal bleeding were
      randomized to four treatment groups (propranolol, propranolol plus isosorbide
      mononitrate, band ligation, band ligation plus propranolol and nitrate) with 40
      patients in each group. Patients were followed for 6 months after the enrolment
      of last patient. Primary end points were recurrence of esophageal variceal
      bleeding and death. Treatment complications were noted. RESULTS: Four treatment
      groups were comparable regarding baseline characteristics. Esophageal variceal
      rebleeding occurred in 22% patients in band ligation plus drugs group, 26%
      patients in drug combination group, 31% patients in banding group and 38%
      patients in propranolol group (p=0.41). Difference in mortality rates was also
      not significant. CONCLUSION: There was no significant difference between
      treatment groups in prevention of esophageal variceal rebleeding.

PMID- 19409160
TI  - Frequency and antimicrobial susceptibility pattern of methicillin resistant
      Staphylococcus aureus.
AB  - OBJECTIVE: To determine the frequency of methicillin resistant Staphylococcus
      aureus and its antimicrobial susceptibility pattern in patients reporting to
      Combined Military Hospital (CMH), Pano Aqil. STUDY DESIGN: A non-interventional,
      cross-sectional study. PLACE AND DURATION OF STUDY: Pathology Laboratory,
      Combined Military Hospital (CMH), Pano Aqil, from December 2005 to January 2008.
      METHODOLOGY: Strains of Staphylococcus aureus were isolated from a variety of
      clinical specimens. Standard methodology, using modified Kirby-Bauer disk
      diffusion method, was adopted for antibiotic sensitivity test. The MIC of
      oxacillin and vancomycin was performed by E-strips, for MRSA isolates and
      isolates revealing vancomycin resistance on disk diffusion. RESULTS: A total of
      195 hospital and 42 community acquired isolates were tested. Forty-seven (19.8%)
      non-duplicate strains were found to be methicillin resistant Staphylococcus
      aureus (MRSA); methicillin resistance did not differ among hospital strains
      (n=42) as compared to community ones (n=5, p=0.1555). No isolates from the
      community and hospital acquired showed resistance to vancomycin. Community and
      hospital acquired isolates revealed higher resistance against penicillin and
      doxycycline than against ciprofloxacin, erythromycin, gentamicin and
      chloramphenicol. However, resistance against these antibiotics did not differ
      significantly among community and hospital acquired isolates. CONCLUSION:
      Increase in prevalence of MRSA is impending in future, appealing preventive
      measures to be adopted. However, Staphylococcus aureus resistant to vancomycin
      was not observed.

PMID- 19409161
TI  - Effect of domestic violence on pregnancy outcome.
AB  - OBJECTIVE: To determine the causes and type of domestic violence endured by
      pregnant women and their effect on pregnancy, in terms of maternal and neonatal
      outcome. STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: The study was
      conducted in Sir Syed Trust Hospital, Karachi, from March 2007 to February 2008.
      METHODOLOGY: All the antenatal patients were screened for domestic violence,
      using a self-made questionnaire and abuse assessment screen. All the pregnant
      patients, who had language barrier or those who declined to be interviewed were
      excluded. All the pregnant patients with positive response, according to the
      abuse assessment screen were included in the group A, while every 4th patient
      with negative response was taken as control. SPSS 10 was used for statistical
      analysis. Logistic regression analysis was performed to determine the effect of
      domestic violence on delivery outcome. Relative risk was also calculated.
      Statistical significance was taken at p (2) 0.05. RESULTS: Four hundred and ten
      (n=410) antenatal patients were interviewed. The factors associated with domestic
      violence included addiction in 32 (39%), allegedly aggressive nature of husband
      in 21 (25.6%) and unemployment of husband in 6 (7.31%) cases (p=0.001). Fifty two
      per cent women had been victims to more than one form of violence. Antenatal
      complications were not observed in a statistically significant number in either
      group. Depression was identified in 25.60% of group A and in 3.65% of group B
      (p=0.001; RR=2.01; 95%CI=1.58-2.56). CONCLUSION: Various factors leading to
      domestic violence were identified among the husbands of women subjected to
      violence during pregnancy. The differences between the two groups, with regard to
      neonatal outcome (except depression), did not reach statistical significance.
      However, depression was significantly higher in the women enduring violence.

PMID- 19409162
TI  - Her-2/neu gene overexpression in breast carcinoma and its association with
      clinicopathological characteristics of the disease.
AB  - OBJECTIVE: To assess the frequency of Her-2/neu gene amplification in breast
      cancer and its association with clinicopathologic characteristics of the disease.
      STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY:
      Study was carried out at Surgical Unit I, Holy Family Hospital, Rawalpindi, from
      January 2005 to December 2006. METHODOLOGY: A total of 50 patients diagnosed of
      having breast cancer on biopsy of breast lump were included in the study. All
      patients underwent mastectomy and samples were submitted to AFIP (Armed Forces
      Institute of Pathology, Rawalpindi) for histopathology and determination of
      estrogen and progesterone receptors and Her-2/neu gene amplification. Moreover,
      association of Her-2/neu amplification to other characteristics like tumour size,
      node involvement, histological grade and presence of estrogen and progesterone
      receptors were also studied. RESULTS: Out of 50 patients, 18 (36%) were positive
      for Her-2/neu overexpression. Among the various prognostic factors, age showed a
      statistically significant relation to Her-2/neu positivity (p=0.001). The Her
      2/neu positive cancers were larger in size (mean size of 7.9 +/- 3.615 and 5.4 +/
      1.906 cm in Her-2/neu positive and negative cases respectively; p=0.002). Her
      2/neu positive cases had statistically significant relation to number of involved
      lymph nodes (mean number of 9.9 and 4.4 lymph nodes in Her-2/neu positive and
      negative cases respectively; p=0.001). Tumour grade and nuclear grade had no
      statistically significant relation to Her-2/neu status (p=0.19 and 0.434
      respectively). Both estrogen and progesterone receptors are inversely related to
      Her-2/neu positivity (p=0.028 and 0.006 respectively). CONCLUSION: The
      pathological and clinical characteristics of Her-2/neu positive and negative
      subsets differ, and Her-2/neu overexpression was associated with other poor
      prognostic factors of age, tumour size and number of nodes involved. There was an
      inverse relation of Her-2/neu status and hormone receptor.

PMID- 19409163
TI  - Family functioning among depressive and dissociative (conversion) patients.
AB  - OBJECTIVE: To campare the family functioning, level of depression, anxiety and
      histrionic personality traits among depressive and dissociative (conversion)
      patients. STUDY DESIGN: A cross-sectional study. PLACE AND DURATION OF STUDY: The
      Psychiatry Unit of Government Lady Reading Hospital, Peshawar, on depressive and
      dissociative (conversion) patients admitted from January to May 2004.
      METHODOLOGY: Purposive sampling technique was used for the assignment of 75
      patients (n=75) with depressive illness and 75 patients (n=75) with dissociative
      (conversion) disorders groups who fulfilled International Statistical
      Classification of Diseases and Related Health Problems, 10th Revision (ICD 10),
      criteria. Test package was administered individually to all the patients and
      scores compared for the groups. RESULTS: On family APGAR scale, no significant
      difference (t=-2.472, p=0.16) was found between the scores of the two groups.
      Patients with depressive illness scored high on Hamilton Rating Scale for
      Depression with mean score of 26.92 and on Hamilton Rating Scale for Anxiety with
      mean score of 23.45, while dissociative group scored high on Hysteria (Hy) sub
      scale of Minnesota Multiphasic Personality Inventory (MMPI) with mean score of
      13.17. CONCLUSION: Dysfunctional family pattern is one of the contributing factor
      in developing and maintaining mental illnesses like depression and dissociative
      (conversion) disorders.

PMID- 19409164
TI  - Presentation and complications of snakebite in a tertiary care hospital.
AB  - OBJECTIVE: To determine frequency of various modes of presentation, complications
      and management of snakebite. STUDY DESIGN: Descriptive case series. PLACE AND
      DURATION OF STUDY: Medical Unit II, Rawalpindi General Hospital, Rawalpindi,
      Pakistan, from September 2006 to August 2007. METHODOLOGY: All patients over 12
      years of age and presenting to emergency department with history of snakebite and
      features of envenomation were included in the study. All these patients were
      given Anti-Snake Venom. Symptomatic treatment of complications was done. Semi
      structured questionnaire was filled during hospital stay to analyze various
      characteristics of snakebite and people's attitude towards this problem. RESULTS:
      A total of 65 patients were enrolled in the study with 40 males (61.5%) and 25
      (38.5%) females. Maximum cases 15 (23%) were seen in the month of August. Age
      group, that was maximally affected, was between 26-30 years (12 cases or 18.5%).
      Only 2 patients had neurotoxic snakebite, whereas rest of the cases were vasculo
      toxic in nature. Gum bleeding and cellulitis were the main presenting complaints.
      Mortality was 4.6% (3 cases). A great majority of patients arrived late in the
      hospital because of lack of awareness and use of traditional though ineffective
      measures. CONCLUSION: Snakebite is a major public health problem. Patients with
      snakebite can be managed effectively provided timely administration of anti-snake
      Venom is done.

PMID- 19409165
TI  - Folic acid and vitamin B6 deficiencies related hyperhomocysteinemia in apparently
      healthy Pakistani adults; is mass micronutrient supplementation indicated in this
      population?
AB  - OBJECTIVE: To determine the plasma/serum levels of homocysteine, and vitamins
      folate, B6 and B12, in Pakistani healthy adults. STUDY DESIGN: Cross-sectional
      study. PLACE AND DURATION OF STUDY: The Aga Khan University, from October 2006 to
      April 2008. METHODOLOGY: Fasting levels of plasma/serum folic acid, pyridoxal
      phosphate (PLP), vitamin B12 and homocysteine were determined in 290 apparently
      healthy hospital personnel from institutions in two cities of Pakistan. Spearman
      correlation test and linear regression analysis was conducted. RESULTS: There
      were 219 males and 71 females with mean age of 46+/-10.5 years and mean body mass
      index of 23.5 +/-3.8. Mean plasma homocysteine levels in Pakistani normal adults
      were found to be 17.95+/-8.4 micromol/l. Mean concentrations of plasma/serum
      folate, vitamin B12 and PLP were found to be 5+/-3.9 ng/ml, 522+/-296 pg/ml and
      21.6+/-14 nmol/l, respectively. Serum/plasma levels of folate, vitamin B12 and
      PLP were negatively correlated with plasma homocysteine (rho coefficient=-0.367,
      p<0.001; -0.173, p=0.004; -0.185, p=0.002, respectively). Serum folate and plasma
      PLP levels were inversely related with plasma homocysteine, adjusted for gender,
      age, smoking and body mass index (p<0.001 and p=0.003, respectively). Percent
      deficiency values of folate, vitamin B6 and vitamin B12 were 39.7%, 52.8% and
      6.6% respectively. CONCLUSION: The high levels of plasma homocysteine could
      indicate a reason for mass micronutrient supplementation to prevent the high
      incidence of cardiovascular disease observed in Pakistani population.

PMID- 19409166
TI  - Sternal tuberculosis discharging through the skin: a rare presentation of
      disseminated tuberculosis.
AB  - Tuberculosis of sternum with skin involvement is a rare manifestation of
      disseminated tuberculosis especially in paediatrics. A 13-year-old girl presented
      with a swelling over the sternum, which had been drained twice and many
      antibiotics had been used without any benefit. On investigations, it turned out
      to be tuberculosis of the sternum. A small, restricted ventricular septal defect
      was also present.

PMID- 19409167
TI  - Hepatic and skeletal metastases from primary intracranial atypical meningioma.
AB  - Meningioma constitutes 27% of primary CNS tumours. It rarely metastasizes to
      distant sites (< 0.1%). Here, we present a case report of primary atypical
      intracranial meningioma metastasizing to liver and bone after 4 years of surgery
      and postoperative radiotherapy presenting with multiple episodes of hypoglycemia.

PMID- 19409168
TI  - Diagnosis and evaluation of Crouzon syndrome.
AB  - Crouzon syndrome is an autosomal dominant condition characterized by
      craniosynostosis with associated dentofacial anomalies. This report describes the
      different clinical features in two affected individuals of different families
      with particular reference to characteristic findings of this syndrome.

PMID- 19409169
TI  - Designer orthopaedic surgery in a patient with anti-Vel antibodies.
AB  - The authors present a rare case of anti-Vel antibodies in a patient who underwent
      a shoulder replacement with a custom designed procedure which involved
      combination of autologous blood pre-deposit, pre-operative haemodilution and
      resurfacing arthroplasty.

PMID- 19409170
TI  - Transverse testicular ectopia.
AB  - A case of transverse testicular ectopia of the left testis is hereby reported. A
      5-year-old boy presented in surgical outpatient department with right inguinal
      hernia and impalpable testis in left scrotum and inguinal canal. Right herniotomy
      was performed. Left testis was found in right superficial inguinal pouch and
      brought to the left scrotum through transceptal window.

PMID- 19409171
TI  - Tension gastrothorax: a rare complication.
AB  - Tension gastrothorax is herniation of abdominal viscera, stomach in particular,
      into the thorax that can simulate acute tension pneumothorax. This case reports
      an acute condition in which percutaneous needle decompression of the distended
      stomach, through the chest wall, allowed rapid decompression of the tension
      gastrothorax. After thoracotomy and repair of the ruptured diaphragm, the patient
      developed re-expansion pulmonary edema that was managed by differential lung
      ventilation.

PMID- 19409172
TI  - Upper gastrointestinal tract endoscopy indications in northern Nigeria.
AB  - Upper gastrointestinal tract endoscopy is one of the commonly performed
      endoscopic procedures, and has only recently become available in Nigeria. The
      indications for upper gastrointestinal tract endoscopy in three health facilities
      in Northern Nigeria were reviewed. Two hundred and sixty-nine patients were found
      to have undergone upper gastrointestinal tract endoscopy. Their ages ranged from
      12-90 years with a mean of 48.1+16.2 years. There were 46.8% males and 53.2%
      females. The commonest indication for the procedure was dyspepsia (61.0%),
      followed by upper gastrointestinal bleeding, gastro-oesophageal reflux disease,
      gastric cancer, gastric outlet obstruction, acute exacerbation of peptic ulcer
      disease, dysphagia, epigastric mass, excessive salivation, abdominal pain,
      anaemia, chronic diarrhoea, haematochexia and persistent vomiting.

PMID- 19409173
TI  - Isolated bony metastasis of malignant pheochromocytoma: a rare clinical entity.

PMID- 19409174
TI  - Pakistani Medical Journals: issue is readership not the revenue.

PMID- 19409175
TI  - [Autophagy: time to degrade to go on living].

PMID- 19409176
TI  - [CD3-specific antibody-induced T-cell apoptosis and apoptotic cell uptake lead to
      CD3-specific antibody-induced tolerance].

PMID- 19409178
TI  - [ALK, a key gene in the pathogenesis of neuroblastoma].

PMID- 19409177
TI  - [Cancer: when recycling becomes a weakness].

PMID- 19409180
TI  - [A contribution of the C. elegans model to the role of glial cells to the
      neuronal response].

PMID- 19409179
TI  - [Human embryonic-stem-cell-derived striatal graft for Huntington's disease cell
      therapy].

PMID- 19409181
TI  - [Glucose homeostasis, diabetes and neurodegenerative disorders].

PMID- 19409182
TI  - [Interleukin-21, new adjuvant for cancer therapy?].

PMID- 19409183
TI  - [Metastatic migration: GEF and GAP show the way].

PMID- 19409184
TI  - [Supply and demand: the influence of energy metabolism on angiogenesis].

PMID- 19409185
TI  - [Impaired autophagy in Crohn's disease patients: an opened gate to invasive
      bacteria?].

PMID- 19409186
TI  - [New strategy for targeting influenza virus replication].

PMID- 19409188
TI  - [Lactoferrin: a multifunctional protein].
AB  - Lactoferrin (Lf) is an iron-binding glycoprotein of the transferrin family that
      is expressed and secreted by glandular cells and found in the secondary granules
      of neutrophils from which it is released in infected tissues and blood during the
      inflammatory process. Initially described as an iron-binding molecule with
      bacteriostatic properties, Lf is now known to be a multifunctional or multi
      tasking protein. It is a major component of the innate immune system of mammals.
      Its protective effects range from direct anti-microbial activities against a
      large panel of microorganisms including bacteria, viruses, fungi, and parasites,
      to anti-inflammatory and anti-cancer activities. While iron chelation is central
      to some of the biological functions of Lf, other activities involve interactions
      of Lf with molecular and cellular components of both hosts and pathogens. Its
      powerful antimicrobial activities, immunomodulatory properties and prevention of
      septic shock, anti-carcinogenic functions and its growing importance in iron
      delivery and bone growth, combined with the data obtained either by in vivo
      studies or clinical trials, make this molecule and its derivatives very promising
      tools for health or nutritional applications.

PMID- 19409189
TI  - [IGF-1 receptors in the brain control longevity in mice].
AB  - Using a mouse model relevant for humans, lifespan can be prolonged by reducing
      IGF-I signaling selectively in the central nervous system. This effect occurred
      through changes in specific neuroendocrine pathways. Investigating the
      pathophysiological mechanism, we found that IGF receptors in the brain steered
      the development of the somatotropic axis, which in turn altered the individual
      growth trajectory and lifespan. Our work is experimental proof that chronically
      low IGF-I and low growth hormone (GH) levels favor long lifespan and postpone age
      related mortality. Our results, together with other recent reports, challenge the
      notion that GH can slow down or prevent human aging. This is important because
      growth hormone is sometimes proposed to elderly people as a substitutive
      treatment in order to compensate the negative effects of aging.

PMID- 19409190
TI  - [Role of histamine and histamine receptors in the pathogenesis of malaria].
AB  - A hallmark of the host response to Plasmodium parasite is an inflammatory
      reaction characterized by elevated histaminemia levels. Since histamine, which
      acts through four different receptors and which synthesis is under the control of
      the histidine decarboxylase (HDC), is endowed with pro-inflammatory and
      immunosuppressive activities, we hypothesized that this vaso-active amine may
      participe to malaria pathogenesis. Combining genetic and pharmacologic approaches
      by using H1R(-/-), H2R(-/-), H3R(-/-), HDC(-/-) mice and H1R, H2R-, and H3R
      antagonists, respectively, we found that cerebral malaria-associated pathogenetic
      processes such as blood brain barrier disruption, and T lymphocyte sequestration
      to cerebral vascular endothelium in mice were associated with histamine
      production. The identification of this novel inflammatory pathway and its
      implication in Plasmodium infection may lead to novel strategies to manipulate
      the anti-Plasmodium immune response and may provide new therapeutic tools to
      alleviate malaria disease.

PMID- 19409191
TI  - [The two faces of autophagy in the nervous system].
AB  - Autophagy is a cellular mechanism for degrading proteins and organelles. It was
      first described as a physiological process essential for maintaining homeostasis
      and cell survival, but understanding its role in conditions of stress has been
      complicated by the recognition of a new type of cell death ("type 2")
      characterized by deleterious autophagic activity. This paradox is important in
      the central nervous system where the activation of autophagy seems to be
      protective in certain neurodegenerative diseases but deleterious in cerebral
      ischemia. The development of new therapeutic strategies based on the manipulation
      of autophagy will need to take into account these opposing roles of autophagy.

PMID- 19409192
TI  - [K+ channels and lung epithelial physiology].
AB  - Transcripts of more than 30 different K(+) channels have been detected in the
      respiratory epithelium lining airways and alveoli. These channels belong to the 3
      main classes of K(+) channels, i.e. i) voltage-dependent or calcium-activated, 6
      transmembrane segments (TM), ii) 2-pores 4-TM and iii) inward-rectified 2-TM
      channels. The physiological and functional significance of this high molecular
      diversity of lung epithelial K(+) channels is not well understood. Surprisingly,
      relatively few studies are focused on K(+) channel function in lung epithelial
      physiology. Nevertheless, several studies have shown that KvLQT1, KCa and K(ATP)
      K(+) channels play a crucial role in ion and fluid transport, contributing to the
      control of airway and alveolar surface liquid composition and volume. K(+)
      channels are involved in other key functions, such as O(2) sensing or the
      capacity of the respiratory epithelia to repair after injury. This mini-review
      aims to discuss potential functions of lung K(+) channels.

PMID- 19409193
TI  - [Immunity in parasite-vector snails].
AB  - Aquatic snails play a key role in the transmission of parasites such as the human
      blood or liver flukes (Schistosomes and Fasciola sp.). During the last decade,
      particular efforts have been made by a small number of scientists to progress in
      our understanding of the molecular mechanisms underlying snail immune responses
      and/or host parasite interactions. Complementary approaches using the gastropod
      snail Biomphalaria glabrata, an intermediate host of Schistosoma mansoni, have
      yielded a number of unexpected results such as the existence of highly
      diversified pathogen-binding proteins (FREPs), or potential immune regulators
      similar to mammalian cytokines. Although molecular immune processes largely
      remain to be elucidated, accumulating data support the idea that snail innate
      immunity is much more complex than originally thought.

PMID- 19409194
TI  - [The immune system of teleost fish].
AB  - Teleosts, the modern branch of bony fishes, make up the richest group among
      Vertebrates with more than 20.000 species displaying considerable diversity and
      found in all aquatic biota. The basal position of fish in vertebrate phylogeny
      makes them very attractive for genomic and functional comparative studies,
      especially of the immune system. Although the rapid evolution of proteins
      involved in immunity and the tumultuous history of fish genomes often obscure the
      identification of orthologous genes, these studies have demonstrated that the
      essential components of the mammalian immune system (macrophages, B and T
      lymphocytes whose receptors undergo V(D)J recombination, MHC, CDs, cytokines,
      interferon pathway...) are present in fish. The discovery of fundamental immune
      mechanisms in fish uncovers the primordial vertebrate immune repertoire ; while
      some unique adaptations also illustrate how a group undergoing adaptative
      radiation may innovate, drawing on the available genomic resources, in response
      to specific constraints.

PMID- 19409195
TI  - [Reception and distribution of the Darwinism in France: Henry de Varigny (1855
      1934), doctor, researcher and journalist, a convinced Darwinian].

PMID- 19409196
TI  - [Maternity for others: from desiring a child to desiring a child at any price].
AB  - Surrogacy is prohibited by French law. On December 17th 2008 the French Court of
      Cassation has refused the transcription on the French register of civil status of
      U.S. birth certificates of children born to a surrogate mother in California.
      Some have been requesting that legislators amend current laws so as to legalize
      the practice. Such a claim is far from unanimous. Two successive reports of the
      French Parliament have underlined their opposition to such modifications: the
      first report has been delivered by a working group of the Senate and the second
      by the Parliamentary Office for Scientific and Technological Choices. We propose
      to analyze the elements that are opposed to the legalization of the practice. We
      do not underestimate the suffering of couples without children or the love they
      want to give but if surrogacy is forbidden it is because of the numerous
      difficulties it entails and that can not be bypassed by sentimental
      considerations.

PMID- 19409197
TI  - [Biomarkers: "Found in translation"].
AB  - Despite continued increase in global Pharma R & D expenditure, the number of
      innovative drugs obtaining market approval has declined since 1994. The
      pharmaceutical industry is now entering a crucial juncture where increasing rates
      of attrition in clinical drug development as well as increasing development
      timelines are impacted by external factors such as intense regulatory pricing and
      safety pressures, increasing sales erosion due to generics, as well as
      exponential increases in the costs of bringing a drug to market. Despite these
      difficulties, numerous opportunities exist such as multiple unmet medical needs,
      the increasing incidence of certain diseases such as Alzheimer's disease, cancer,
      diabetes and obesity due to demographic changes, as well as the emergence of
      evolving markets such as China, India, and Eastern Europe. Consequently, Pharma
      is now responding to this challenge by improving both the productivity and the
      innovation in its drug discovery and development pipelines. In this regard, the
      advent of new technologies and expertise such as genomics, proteomics, structural
      biology, and molecular informatics in an integrated systems biology approach also
      provides a powerful opportunity for Pharma to address some of these difficulties.
      The key features behind this new strategy imply a discovery process based on an
      improved understanding of the molecular mechanism of diseases and drugs,
      translational research that places the patient at the center of the research
      process, and the application of biomarkers throughout the discovery and
      development phases. Moreover, new paradigms are required to improve target
      validation and develop more predictive cellular and animal models of human
      pathologies, a greater capacity in informatics-based analysis, and, consequently,
      a greater access to the vast sources of accumulating biological data and its
      integrated analysis. In the present review, we will address some of these issues
      and in particular emphasize how the application of biomarkers could potentially
      lead to improved productivity, quality, and innovation in drug discovery and
      ultimately better and safer medicines with improved therapeutic efficacy in
      specific pathologies for targeted patients.

PMID- 19409198
TI  - Use of spermatozoal mRNA profiles to study gene-environment  interactions in
      human germ cells.
AB  - Paternal exposure to genotoxic compounds is thought to contribute to diseases in
      their offspring. Therefore, it is of importance to develop biomarkers of male
      germ cell exposure to genotoxins. Unfortunately, the testis cannot be reached for
      routine biomonitoring, but mRNA-profiles in spermatozoa may reflect the processes
      that have occurred in the testis after exposures to genotoxins, since spermatozoa
      are largely transcriptionally inactive. Therefore, mRNA profiles from sperm in
      ejaculates of cigarette smokers (N=4) were compared with non-smokers (N= 4).
      Smoking behaviour was verified by assessing cotinine levels in seminal plasma.
      High expression of the germ cell specific gene protamine 2 (PRM2) was observed in
      spermatozoal mRNA isolates by Q-PCR, which was absent in reference mRNA isolates
      obtained from a pool of other organs. Gene-expression analysis was subsequently
      performed using microarray technology and a total of 781 genes were found to be
      differentially expressed in spermatozoa of smokers compared to non-smokers (fold
      change >40%; p < 0.05). To further limit the number of false positive results,
      genes were additionally selected on basis of the correlation between their
      expression levels with cotinine concentrations in seminal plasma (r > 0.80 as
      arbitrary cut-off value, p < 0.05), and a total of 200 transcripts remained, of
      which the germ cell specific transcription factor SALF was the highest up
      regulated gene (5.4-fold) and the zinc finger encoding gene TRIM26 most down
      regulated (7.4-fold). Although no altered pathways could be identified for the
      differentially expressed genes, an enrichment was observed for NF-kappaB
      regulated genes (46% vs. 27%, p = 0.004) playing a central role in stress
      response. Accordingly, subsequent analysis of transcription factor networks
      suggests that apoptosis was inhibited in smokers. These data show the feasibility
      of using gene-expression profiles in mature sperm to elucidate gene-environment
      interactions in male testis.

PMID- 19409199
TI  - An Ang1-Tie2-PI3K axis in neural progenitor cells initiates survival responses
      against oxygen and glucose deprivation.
AB  - Neural progenitor cells (NPCs) have the potential to survive brain ischemia and
      participate in neurogenesis after stroke. However, it is not clear how survival
      responses are initiated in NPCs. Using embryonic mouse NPCs and the in vitro
      oxygen and glucose deprivation (OGD) model, we found that angiopoietin-1 (Ang1)
      could prevent NPCs from OGD-induced apoptosis, as evidenced by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling and annexin V
      labeling. Ang1 significantly elevated tunica intima endothelial kinase 2 (Tie2)
      autophosphorylation level, suggesting the existence of functional Tie2 receptors
      on NPCs. NPCs under OGD conditions exhibited reduction of Akt phosphorylation,
      decrease of the Bcl-2/Bax ratio, activation of caspase-3, cleavage of PARP, and
      downregulation of beta-catenin and nestin. Ang1 reversed the above changes
      concomitantly with significant rising of survival rates of NPCs under OGD, but
      all these effects of Ang1 could be blocked by either soluble extracellular domain
      of Tie2 Fc fusion protein (sTie2Fc) or the phosphoinositide 3-kinase (PI3K)
      inhibitor 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one (LY294002). Our
      findings suggest the existence of an Ang1-Tie2-PI3K signaling axis that is
      essential in initiation of survival responses in NPCs against cerebral ischemia
      and hypoxia.

PMID- 19409200
TI  - Gestational hypoxia alone or combined with restraint sensitizes the hypothalamic
      pituitary-adrenal axis and induces anxiety-like behavior in adult male rat
      offspring.
AB  - We have reported that hypoxia affects the hypothalamic-pituitary-adrenal (HPA)
      axis and behavior by driving the expression of central corticotropin-releasing
      hormone (CRH) and its receptors in adult mammals, and this effect is modulated by
      other factors. Here, we address whether or not intermittent hypoxia (IH) or
      restraint (R) or a combination of both (IH+R) during gestation would result in
      differential alteration of the HPA axis and behavior of the adult male offspring.
      Gravid rats were exposed to IH in a hypobaric chamber (10.8% O(2), altitude of 5
      km), R, or both, daily for 4 h for 21 days. Control parameters were set at sea
      level (20.9% O(2)). All the stressors significantly and differentially increased
      CRH and corticotropin-releasing factor receptor type 1 (CRHR1) expression but
      decreased corticotropin-releasing factor receptor type 2 (CRHR2) in the
      paraventricular nucleus of the hypothalamus (PVN), enhanced CRHR1 mRNA and CRHR2
      mRNA expression in the anterior pituitary, and increased plasma
      adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels and adrenal
      weight in adult male offspring aged 120 days. Furthermore, norepinephrine (NE)
      and dopamine (DA) levels significantly increased in the locus coeruleus (LC),
      while the percentage of entries into the open arms of the elevated-plus maze test
      (EPM) markedly declined. In all the above effects, the combination-induced effect
      was stronger than each stressor alone. Confocal imaging showed a rich
      colocalization of CRHR1 with CRH or urocortin I (Ucn I), and CRHR2 with CRH or
      urocortin III (Ucn III) in the PVN, and CRHR1 with CRH in the LC in EPM-tested
      groups. In conclusion, IH or R alone or both in combination during gestation
      sensitize the HPA axis and induce anxiety-like behavior of the adult male
      offspring, and the combined effects are significantly great than IH or R alone.
      The CRH-NE neural circuit between the PVN and LC through CRH receptor driving
      might partly be involved in the effects. The differential colocalization of CRH
      with CRHR1 might be the neural basis of these effects.

PMID- 19409201
TI  - The physiological role of pre- and postsynaptic GABA(B) receptors in membrane
      excitability and synaptic transmission of neurons in the rat's dorsal cortex of
      the inferior colliculus.
AB  - In the inferior colliculus (IC), GABAergic inhibition mediated by GABA(A)
      receptors has been shown to play a significant role in regulating physiological
      responses, but little is known about the physiological role of GABA(B) receptors
      in IC neurons. In the present study, we used whole-cell patch clamp recording in
      vitro to investigate the effects of activation of GABA(B) receptors on membrane
      excitability and synaptic transmission of neurons in the rat's dorsal cortex of
      the inferior colliculus (ICD). Repetitive stimulation of GABAergic inputs to ICD
      neurons at high frequencies could elicit a slow and long-lasting postsynaptic
      response, which was reversibly abolished by the GABA(B) receptor antagonist, CGP
      35348. The results suggest that postsynaptic GABA(B) receptors can directly
      mediate inhibitory synaptic transmission in ICD. The role of postsynaptic GABA(B)
      receptors in regulation of membrane excitability was further investigated by
      application of the GABA(B) receptor agonist, baclofen. Baclofen hyperpolarized
      the cell, reduced the membrane input resistance and firing rate, increased the
      threshold for generating action potentials (APs), and decreased the amplitude of
      the AP and its associated after-hyperpolarization. The Ca2+-mediated rebound
      depolarization following hyperpolarization and the depolarization hump at the
      beginning of membrane depolarization were also suppressed by baclofen. In voltage
      clamp experiments, baclofen induced inward rectifying K+ current and reduced low-
      and high-threshold Ca2+ currents, which may account for the suppression of
      membrane excitability by postsynaptic GABA(B) receptors. Application of baclofen
      also reduced excitatory synaptic responses mediated by alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptors, and inhibitory synaptic
      responses mediated by GABA(A) receptors. Baclofen increased the ratios of 2nd/1st
      excitatory and inhibitory postsynaptic currents to paired-pulse stimulation of
      the synaptic inputs. These results suggest that fast glutamatergic and GABAergic
      synaptic transmission in ICD can be modulated by presynaptic GABA(B) receptors.

PMID- 19409202
TI  - Molecular development of the lateral geniculate nucleus in the absence of retinal
      waves during the time of retinal axon eye-specific segregation.
AB  - When retinal waves are inhibited binocularly, eye-specific segregation of retinal
      axons is disrupted, and retinal axons from the two eyes remain intermingled in
      the lateral geniculate nucleus (LGN). This effect of binocular retinal wave
      inhibition is mediated by the lack of activity-dependent competition between
      retinal axons from the two eyes, but it is unknown whether this effect is also
      mediated by the developmental arrest of the LGN in an immature state. Here we
      find developmental markers of the LGN during eye-specific segregation. The
      expression levels of Purkinje cell protein 4 (PCP4/PEP19), transcription factor 7
      like 2 (TCF7L2/TCF4) and LIM homeobox protein 9 (Lhx9) in the LGN change
      significantly during eye-specific segregation. Using PCP4, TCF7L2 and Lhx9 as
      developmental markers of the LGN, we examine whether LGN development is affected
      by binocular disruption of retinal waves during eye-specific segregation.
      Binocular injection of epibatidine strongly inhibits eye-specific segregation,
      whereas it does not affect the expression of PCP4, TCF7L2 and Lhx9. Furthermore,
      the expression of PCP4, TCF7L2 and Lhx9 is normal in binocularly enucleated
      animals and in mice treated with the monoamine oxidase A (MAOA) inhibitor,
      clorgyline. In addition, our experiments using LGN slice cultures show that the
      expression of PCP4 and TCF7L2 in LGN slices changes as in vivo. Our results
      suggest that LGN development proceeds, at least in part, even in the absence of
      retinal inputs. PCP4, TCF7L2 and Lhx9 should be useful to examine LGN development
      during eye-specific segregation in mice and in ferrets.

PMID- 19409203
TI  - The role of spinal orexin-1 receptors in posterior hypothalamic modulation of
      neuropathic pain.
AB  - The posterior hypothalamus (PH) is known to reduce nociceptive pain, but the
      effect of PH stimulation on neuropathic pain is not known. Because neurons
      containing the neurotransmitter orexin-A are located in the PH in some strains of
      rat and intrathecal injection of orexin-A produces antinociception in a
      neuropathic pain model, we hypothesized that orexin-A from neurons in the PH
      modifies nociception in the spinal cord dorsal horn. To test this hypothesis, the
      cholinergic agonist carbachol or normal saline was microinjected into the PH of
      lightly anesthetized female Sprague-Dawley rats with chronic constriction injury
      (CCI) and foot withdrawal latencies (FWL) were measured. Carbachol-induced PH
      stimulation produced dose dependent antinociception as shown by significantly
      increased FWL compared to saline controls. To investigate the role of orexin-A in
      PH-induced antinociception, the orexin-1 receptor antagonist SB-334867 or
      dimethyl sulfoxide (DMSO) for control, was given intrathecally following
      carbachol-induced PH stimulation. SB-334867 decreased FWL compared to DMSO
      controls. These data are suggestive that stimulating the PH produces
      antinociception in a neuropathic pain model and that the antinociceptive effect
      is mediated in part by orexin-1 receptors in the spinal cord dorsal horn.

PMID- 19409205
TI  - Bacopa monniera alleviates N(omega)-nitro-L-arginine arginine-induced but not MK
      801-induced amnesia: a mouse Morris watermaze study.
AB  - N-methyl-D-aspartate (NMDA) receptor and nitricoxide syntheses are the emerging
      target sites for development of novel drug molecules because their modulation
      affects the long term potentiation (LTP) process. NMDA receptor antagonists and
      nitric oxide synthase inhibitors induce amnesia in animals and therefore have
      been employed for evaluation of efficacy of several novel antiamnesic
      agents.Bacopa monniera Linn (syn. Brahmi) is commonly used in the ancient Indian
      medical system for improvement of memory deficit.We have earlier described the
      involvement of GABAergic and cholinergic system to account for the antiamnesic
      effects of B. monniera on diazepam- and scopolamine-induced amnesia.In extension
      to our previous study this study was designed to investigate the downstream
      mechanism of B. monniera by evaluation of its effect on MK-801 (an NMDA receptor
      antagonist) and N(w)-nitro-L-arginine (L-NNA) (a nitric oxide inhibitor)induced
      memory deficit. We used a Morris water maze scale and compared the degree of
      reversal of amnesia induced by the two agents. Male Swiss albino mice were
      subjected to a Rotarod muscle incoordination test followed by water maze
      tasks.Our data revealed that L-NNA and MK-801 produced anterograde and retrograde
      amnesia and B. monniera significantly attenuated the L-NNA-induced anterograde
      amnesia, partially reversing L-NNA-induced retrograde amnesia. On the other hand,
      B. monniera neither attenuated the MK-801-induced anterograde amnesia nor
      improved retrograde amnesia caused by it.

PMID- 19409204
TI  - Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity.
AB  - Increased caloric intake in dietary obesity could be driven by central mechanisms
      that regulate reward-seeking behavior. The mesolimbic dopamine system, and the
      nucleus accumbens in particular, underlies both food and drug reward. We
      investigated whether rat dietary obesity is linked to changes in dopaminergic
      neurotransmission in that region. Sprague-Dawley rats were placed on a cafeteria
      style diet to induce obesity or a laboratory chow diet to maintain normal weight
      gain. Extracellular dopamine levels were measured by in vivo microdialysis.
      Electrically evoked dopamine release was measured ex vivo in coronal slices of
      the nucleus accumbens and the dorsal striatum using real-time carbon fiber
      amperometry. Over 15 weeks, cafeteria-diet fed rats became obese (>20% increase
      in body weight) and exhibited lower extracellular accumbens dopamine levels than
      normal weight rats (0.007+/-0.001 vs. 0.023+/-0.002 pmol/sample; P<0.05).
      Dopamine release in the nucleus accumbens of obese rats was stimulated by a
      cafeteria-diet challenge, but it remained unresponsive to a laboratory chow meal.
      Administration of d-amphetamine (1.5 mg/kg i.p.) also revealed an attenuated
      dopamine response in obese rats. Experiments measuring electrically evoked
      dopamine signal ex vivo in nucleus accumbens slices showed a much weaker response
      in obese animals (12 vs. 25x10(6) dopamine molecules per stimulation, P<0.05).
      The results demonstrate that deficits in mesolimbic dopamine neurotransmission
      are linked to dietary obesity. Depressed dopamine release may lead obese animals
      to compensate by eating palatable "comfort" food, a stimulus that released
      dopamine when laboratory chow failed.

PMID- 19409207
TI  - Differences in Ca2+ regulation for high-output Is and low-output Ib motor
      terminals in Drosophila larvae.
AB  - We determined whether two classes of Drosophila larval motor terminals with known
      differences in structure and transmitter release also showed differences in
      Ca(2+) regulation. Larval motor neurons can be separated into those producing
      large synaptic boutons (Ib) and those with small boutons (Is). Ib terminals
      release less transmitter during single action potentials (APs) than Is terminals,
      but show greater facilitation during high-frequency stimulation. We measured
      Ca(2+) transients produced by single APs and AP trains after loading the
      terminals with the dextran-conjugated Ca(2+) indicator Oregon Green 488 BAPTA-1
      (OGB-1). The two pairs of Is and Ib terminals innervating muscle fiber 4 and
      fibers 6 and 7 were examined. The OGB-1 concentrations were measured in order to
      compare measurements from terminals with similar OGB-1 loading. For single APs,
      the change in OGB-1 fluorescence (DeltaF/F) in Is boutons was significantly
      larger than in Ib boutons due to greater Ca(2+) influx per bouton volume. The Is
      boutons had greater surface area and active zone number per bouton volume than Ib
      boutons; this could account for the differences in Ca(2+) influx and argues for
      similar Ca(2+) influx at Is and Ib active zones. As previously reported for the
      Ib boutons, the distal Is boutons had larger single-AP Ca(2+) transients than
      proximal ones on muscle fibers 6 and 7, but not on fiber 4. This difference was
      not due to proximal-distal differences in surface area or active zones per bouton
      volume and may be due to greater Ca(2+) influx at distal active zones. During AP
      trains, the Is Ca(2+) transients were larger in amplitude and had longer decay
      time constants than Ib ones. This can be explained by a slower rate of Ca(2+)
      extrusion from the Is boutons apparently due to lower plasma membrane Ca(2+)
      ATPase activity at Is boutons compared to Ib boutons.

PMID- 19409206
TI  - Long-term administration of green tea catechins prevents age-related spatial
      learning and memory decline in C57BL/6 J mice by regulating hippocampal cyclic
      amp-response element binding protein signaling cascade.
AB  - Flavonoid-rich foods have been shown to be effective at reversing age-related
      deficits in learning and memory in both animals and humans. However, little
      investigation of the preventative effects of flavonoids on the naturally aged
      animals was reported. In our study, 14-month-old female C57BL/6 J mice were
      orally administered 0.025%, 0.05% and 0.1% green tea catechins (GTC, w/v) in
      drinking water for 6 months; we found that a supplementation with 0.05% or 0.1%
      GTC prevented age-related spatial learning and memory decline of mice in the
      Morris water maze. Better performance of GTC-treated mice was associated with
      increased levels of cAMP-response element binding protein (CREB) phosphorylation
      in the hippocampus. The expressions of brain-derived neurotrophic factor (BDNF)
      and Bcl-2, two target genes of CREB which can exhibit long-term regulatory roles
      in synaptic plasticity and synaptic structure, were also increased. We also found
      that long-term 0.05% or 0.1% GTC administration prevented age-related reductions
      of two representative post-synaptic density proteins PSD95 and Ca(2+)/calmodulin
      dependent protein kinase II, suggesting that synaptic structural changes may be
      involved. These results demonstrated that long-term 0.05% or 0.1% green tea
      catechin administration may prevent age-related spatial learning and memory
      decline of female C57BL/6 J mice by regulating hippocampal CREB signaling
      cascade.

PMID- 19409209
TI  - Early frequency-dependent information processing and cortical control in the
      whisker pathway of the rat: electrophysiological study of brainstem nuclei
      principalis and interpolaris.
AB  - The rat facial whiskers form a high-resolution sensory apparatus for tactile
      information coding and are used by these animals for the exploration and
      perception of their environment. Previous work on the rat vibrissae system
      obtained evidence for vibration-based feature extraction by the whiskers, texture
      classification by the cortical neurons, and "low-pass", "high-pass", and "band
      pass" filtering properties in both thalamic and cortical neurons. However, no
      data are available for frequency-dependent information processing in the
      brainstem sensory trigeminal complex (STC), the first relay station of the
      vibrissae pathway. In the present paper, we studied the frequency-dependent
      processing characteristics of the STC nuclei that mainly project to the thalamus,
      nuclei principalis, and interpolaris. This is the first time that STC nuclei have
      been studied together via a wide range of stimulation frequencies (1-40 Hz), four
      different and complementary metrics, and the same experimental protocol.
      Moreover, the role of corticofugal projection to these nuclei as well as the
      influence of input from the whiskers has been analyzed. We show that both nuclei
      perform frequency-dependent coding of tactile information: low pass and band-pass
      filtering occurs for the spiking rate in short post-stimuli time intervals, high
      pass and band-pass filtering occurs for the spiking rate in long trains of
      stimuli, and an increase of response latencies and low pass filtering occurs for
      phase-locked stimuli. These information-processing characteristics are neither
      imposed by the sensorimotor cortex nor introduced by the afferent fibres. The
      sensorimotor cortex exerts a distinct modulatory effect on each nucleus.

PMID- 19409208
TI  - Gene expression in the suprachiasmatic nuclei and the photoperiodic time
      integration.
AB  - In mammals, the 24 h-rhythmicity of many physiological events is driven by the
      circadian clock contained in the suprachiasmatic nuclei (SCN). In the SCN, clock
      gene expressions produce the rhythmicity and control the expression of clock
      controlled genes which play a role in the distribution of daily messages. The
      daily expression of all these genes is modulated by the duration of the light
      phase (i.e. photoperiod). The aim of this study was first to determine if these
      daily changes of expression reflect a real integration of a new photoperiod by
      the circadian clock or reflect only a passive effect of the light. In this way,
      we performed a time course of the modifications of gene expression after a
      transfer of Syrian hamsters from long to short photoperiod (LP and SP). Our
      results demonstrate that the core of the SCN (clock genes) integrates quickly a
      new photoperiod which entrains a slow adaptation of the clock-controlled gene
      expressions and induces a differential daily functioning of an SCN-target tissue,
      the pineal gland. We next asked the question whether SCN are involved in the
      photorefractory phase observed in Syrian hamsters exposed to SP for 26 weeks. All
      genes analyzed present a similar daily expression in SP-refractory and in SP with
      the exception of Clock. Its particular expression in SP-refractory is different
      than ones observed in SP or in LP. Thus, Clock seems to play a role in the
      development of the photorefractory phase, or this physiological state may modify
      the expression of Clock in the SCN. As a conclusion, it appears that the
      photoperiodic time measurement involves daily modifications of the molecular
      functioning of the SCN and that SCN also play a role in the measurement of the
      duration of the time passed in a short photoperiod.

PMID- 19409210
TI  - Neuroprotective effects of yokukansan, a traditional Japanese medicine, on
      glutamate-mediated excitotoxicity in cultured cells.
AB  - To clarify the mechanism of yokukansan (TJ-54), a traditional Japanese medicine,
      against glutamate-mediated excitotoxicity, the effects of TJ-54 on glutamate
      uptake function were first examined using cultured rat cortical astrocytes. Under
      thiamine-deficient conditions, the uptake of glutamate into astrocytes, and the
      levels of proteins and mRNA expressions of glutamate aspartate transporter of
      astrocytes significantly decreased. These decreases were ameliorated in a dose
      dependent manner by treatment with TJ-54 (100-700 microg/ml). The improvement of
      glutamate uptake with TJ-54 was completely blocked by the glutamate transporter
      inhibitor DL-threo-beta-hydroxyaspartic acid. Effects of TJ-54 on glutamate
      induced neuronal death were next examined by using cultured PC12 cells as a model
      for neurons. Addition of 17.5 mM glutamate to the culture medium induced an
      approximately 50% cell death, as evaluated by the 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay. TJ-54 (1-1000 microg/ml) inhibited the
      cell death in a dose-dependent manner. Furthermore, competitive binding assays to
      glutamate receptors showed that TJ-54 bound potently to N-methyl-D-aspartate
      receptors, in particular, to its glutamate and glycine recognition sites. These
      results suggest that TJ-54 may exert a neuroprotective effect against glutamate
      induced excitotoxicity not only by amelioration of dysfunction of astrocytes but
      also by direct protection of neuronal cells.

PMID- 19409211
TI  - Quantification of gray matter changes in the cerebral cortex after isolated
      cerebellar damage: a voxel-based morphometry study.
AB  - There is growing evidence based on behavioral and functional imaging studies
      about the cerebellar involvement in the modulation of cognitive functions.
      However, it still remains to be clarified how the cerebellum interacts with brain
      regions sub-serving different cognitive domains. In this study we used magnetic
      resonance imaging (MRI) and voxel based morphometry (VBM) to investigate changes
      of cerebral gray matter (GM) density in 15 patients with a focal cerebellar
      damage (CD) compared to 15 healthy controls. T2-weighted scans and T1-weighted
      volumes were collected from each subject. With the exception of the cerebellar
      lesion, none of the patients showed any additional brain MRI abnormality. T1
      volumes were analyzed by voxel-based morphometry. Consistent with their
      neuropsychological abnormalities, patients with right-CD compared to controls
      showed a reduction of GM density mainly involving the left frontal, parietal and
      temporal lobes. Conversely, patients with left-CD did not show any significant
      neuropsychological or cerebral GM abnormality. The present study indicates that
      specific GM changes may be detected in patients with isolated CD and cognitive
      dysfunction. We discuss the findings in terms of cerebellar influence on the
      neuronal networks involved in higher level functions of the association cortex.

PMID- 19409212
TI  - Pair bonding in the female zebra finch: a potential role for the nucleus taeniae.
AB  - Male and female zebra finches are highly social and form pair bonds typically
      associated with reproduction. To determine how these bonds affect a female's
      behavioral response to future interactions, females were paired with a male for 2
      weeks, separated for 48 h, and then exposed to the same or a novel male. Control
      females were left unpaired and introduced to a novel male. Behaviors, as well as
      neural ZENK expression, were quantified. Females displayed higher levels of
      behaviors associated with pair bonds (clumping and preening) toward their mates
      than novel males, and display of these behaviors was correlated with expression
      of the immediate early gene ZENK in the nucleus taeniae of one group of females,
      those interacting with their mates. Behaviors of the stimulus males were largely
      unaffected, but those interacting with an unpaired female attempted to mount more
      than those interacting with their mates. The results indicate that the nucleus
      taeniae may play some role in the maintenance of pair bonds in this species.
      Additionally, females may provide some signal to influence elements of the
      behavior of males.

PMID- 19409213
TI  - Neurochemical and behavioral alterations in an inflammatory model of depression:
      sex differences exposed.
AB  - It is firmly established that women experience major depression (MD) at roughly
      twice the rate of men and that dysregulation of the immune system is associated
      with the appearance and course of this condition. In the present study, we sought
      to identify whether "sickness behavior", an inflammatory model of MD, is
      characterized by sexual dimorphism by focusing on both neurochemical and
      behavioral responses. Therefore, we investigated the serotonergic and
      dopaminergic activity of various brain regions implicated in the pathophysiology
      of affective disorders (hypothalamus, hippocampus, prefrontal cortex, amygdala
      and striatum) in response to a mild lipopolysaccharide (LPS) challenge, in rats
      of both sexes. According to our results, at 2 h post-LPS administration (100
      microg/kg i.p.), the neurochemical substrate was primarily altered in female rats
      with the serotonergic function being markedly enhanced in all brain regions
      examined. Dopaminergic activation following immune system sensitization with LPS
      was not apparent in male rats and only modest in female rats with the exception
      of striatum. LPS administration also affected sickness-associated behaviors to a
      different extent in male and female rats, as assessed in the forced swim test
      (FST), the hot plate test (HPT) and the open-field arena. LPS-treated female rats
      coped better with the stressful FST procedure, as evidenced by an increase in
      swimming duration. The effects of LPS treatment appeared to be more robust in
      male rats, as far as suppression of locomotor activity is concerned, while the
      antinociceptive properties of LPS were evident in both sexes though showing sex
      dependent kinetics. Moreover, when traditional measures of sickness (i.e. sucrose
      consumption, social exploration, food intake) were assessed, males and females
      appeared to be similarly affected, except for food intake. These data are the
      first to demonstrate that the serotonergic system is affected to a greater extent
      in female rats at 2 h post-LPS administration and further contribute to our
      understanding regarding sexual dimorphism upon sickness establishment.

PMID- 19409214
TI  - Immediate integration of prosodic information from speech and visual information
      from pictures in the absence of focused attention: a mismatch negativity study.
AB  - Language is often perceived together with visual information. Recent experimental
      evidences indicated that, during spoken language comprehension, the brain can
      immediately integrate visual information with semantic or syntactic information
      from speech. Here we used the mismatch negativity to further investigate whether
      prosodic information from speech could be immediately integrated into a visual
      scene context or not, and especially the time course and automaticity of this
      integration process. Sixteen Chinese native speakers participated in the study.
      The materials included Chinese spoken sentences and picture pairs. In the
      audiovisual situation, relative to the concomitant pictures, the spoken sentence
      was appropriately accented in the standard stimuli, but inappropriately accented
      in the two kinds of deviant stimuli. In the purely auditory situation, the speech
      sentences were presented without pictures. It was found that the deviants evoked
      mismatch responses in both audiovisual and purely auditory situations; the
      mismatch negativity in the purely auditory situation peaked at the same time as,
      but was weaker than that evoked by the same deviant speech sounds in the
      audiovisual situation. This pattern of results suggested immediate integration of
      prosodic information from speech and visual information from pictures in the
      absence of focused attention.

PMID- 19409217
TI  - Mapping genetic influences on the corticospinal motor system in humans.
AB  - It is becoming increasingly clear that genetic variations account for a certain
      amount of variance in the acquisition and maintenance of different skills. Until
      now, several levels of genetic influences were examined, ranging from global
      heritability estimates down to the analysis of the contribution of single
      nucleotide polymorphisms (SNP) and variable number tandem repeats. In humans, the
      corticospinal motor system is essential to the acquisition of fine manual motor
      skills which require a finely tuned coordination of activity in distal forelimb
      muscles. Here we review recent brain mapping studies that have begun to explore
      the influence of functional genetic variation as well as mutations on function
      and structure of the human corticospinal motor system, and also the clinical
      implications of these studies. Transcranial magnetic stimulation of the primary
      motor hand area revealed a modulatory role of the common val66met polymorphism in
      the BDNF gene on corticospinal plasticity. Diffusion-sensitive magnetic resonance
      imaging has been employed to pinpoint subtle structural changes in corticospinal
      motor projections in individuals carrying a mutation in genes associated with
      motor neuron degeneration. These studies underscore the potential of non-invasive
      brain mapping techniques to characterize the genetic influence on the human
      corticospinal motor system.

PMID- 19409216
TI  - Regulation of hind-limb tone by adenosine A2A receptor in rats.
AB  - Adenosine A2A receptor agonists produce a hypokinetic state (catalepsy) that is
      believed to reflect antagonistic interaction of A2A and dopamine D2 receptors in
      the basal ganglia. In addition to catalepsy, pharmacological blockade of D2
      receptors produces rigidity. However there are conflicting data about the effect
      of A2A agonists on muscle tone, with some reports indicating an increase, while
      other data suggest that A2A catalepsy is dominated by muscle hypotonia. We
      investigated the effect on resistance to imposed movements of systemic cataleptic
      doses of the selective A2A agonist CGS21680 (5 mg/kg), and compared it with the
      effect of the D2 antagonist raclopride (5 mg/kg), in rats. Total resistance is
      made up of elastic and viscous components. The elastic component is velocity
      independent, and is referred to as "stiffness," whereas viscosity, which dampens
      responses to imposed movements, is velocity dependent. Using a method for
      quantifying total joint resistance that enabled separate identification of
      stiffness and viscosity, we found that during catalepsy evoked by either drug
      there was a clear increase in joint rigidity. Both CGS21680 and raclopride
      significantly increased joint stiffness, the velocity independent component of
      rigidity that is most affected in Parkinsonism. In contrast, the effect of
      CGS21680 on the velocity-dependent viscosity component was less robust than for
      raclopride, and did not reach significance, possibly reflecting an interaction
      with sedative effects via extrastriatal receptors. The effect of CGS21680 and
      raclopride on joint stiffness is thus consistent with previous findings
      suggesting functional antagonism of A2A and D2 receptors in the basal ganglia.

PMID- 19409218
TI  - Cerebellum and emotional behavior.
AB  - Fear conditioning involves learning that a previously neutral stimulus (CS)
      predicts an aversive unconditioned stimulus (US). Lesions of the cerebellar
      vermis may affect fear memory without altering baseline motor/autonomic responses
      to the frightening stimuli. Reversible inactivation of the vermis during the
      consolidation period impairs retention of fear memory. In patients with medial
      cerebellar lesions conditioned bradycardia is impaired. In humans, cerebellar
      areas around the vermis are activated during mental recall of emotional personal
      episodes, if a loved partner receives a pain stimulus, and during learning of a
      CS-US association. Moreover, patients with cerebellar stroke may fail to show
      overt emotional changes. In such patients, however, the activity of several
      areas, including ventromedial prefrontal cortex, anterior cingulate, pulvinar and
      insular cortex, is significantly increased relative to healthy subjects when
      exposed to frightening stimuli. Therefore, other structures may serve to maintain
      fear response after cerebellar damage. These data indicate that the vermis is
      involved in the formation of fear memory traces. We suggest that the vermis is
      not only involved in regulating the autonomic/motor responses, but that it also
      participates in forming new CS-US associations thus eliciting appropriate
      responses to new stimuli or situations. In other words, the cerebellum may
      translate an emotional state elaborated elsewhere into autonomic and motor
      responses.

PMID- 19409215
TI  - Long-term potentiation of the responses to parallel fiber stimulation in mouse
      cerebellar cortex in vivo.
AB  - Long-term potentiation (LTP) of parallel fiber-Purkinje cell (PF-PC) synapses in
      the cerebellum has been suggested to underlie aspects of motor learning. Previous
      in vitro studies have primarily used low frequency PF stimulation conditioning
      paradigms to generate either presynaptic PF-PC LTP (4-8 Hz) or postsynaptic PF-PC
      LTP (1 Hz). Little is known about the conditions that evoke PF-PC LTP in vivo.
      High frequency stimulation in vivo increases PC responsiveness to peripheral
      stimuli; however, neither the site of action nor the signaling pathways involved
      have been examined. Using flavoprotein autofluorescence optical imaging in the
      FVB mouse in vivo, this report describes that a conditioning stimulation
      consisting of a high frequency burst of PF stimulation (100 Hz, 15 pulse trains
      every 3 s for 5 min) evokes a long-term increase in the response to PF
      stimulation. Following the conditioning stimulation, the response to PF
      stimulation increases over 20 min to approximately 130% above baseline and this
      potentiation persists for at least 2 h. Field potential recordings of the
      responses to PF stimulation show that the postsynaptic component is potentiated
      but the presynaptic, parallel fiber volley is not. Paired-pulse facilitation does
      not change after the conditioning stimulation, suggesting the potentiation occurs
      postsynaptically. Blocking non-NMDA (N-methyl-d-aspartic acid) ionotropic
      glutamate receptors with DNQX (6,7-dinitroquinoxaline-2,3-dione disodium salt, 50
      muM, bath application) during the conditioning stimulation has no effect on the
      long-term increase in fluorescence. However, blocking subtype I metabotropic
      glutamate receptors (mGLuR(1)) with LY367385 (200 muM) during the conditioning
      stimulation abolishes the long-term increase in fluorescence. Blocking GABAergic
      neurotransmission is not required to evoke this long-term potentiation. Blocking
      GABA(A) receptors reduces but does not eliminate the long-term potentiation.
      Therefore, this study demonstrates that high frequency PF stimulation generates
      long-term potentiation of PF-PC synapses in vivo. This novel form of LTP is
      generated primarily postsynaptically and is mediated by mGluR(1) receptors.

PMID- 19409220
TI  - Imaging genetics and the power of combined technologies: a perspective from
      neuroethics.
AB  - Imaging genetics has emerged as a powerful and sensitive approach to the study of
      functional genetic variations and brain responses in psychiatric and neurologic
      disorders. Ethics issues in contemporary neuroscience as they apply separately to
      genetics and neuroimaging have been a growing focus for research but, to date,
      there has not yet been a rigorous exploration of the ethical dimensions of the
      territory in which they overlap. Here we propose that the ethics challenges
      associated with the combination of these methods call for an expanded "neuro
      space" in which societal and ethical values are closely and explicitly integrated
      with the new science. We build specifically on the model delivered by Roffman et
      al. [Roffman JL, Weiss AP, Goff DC, Rauch SL, Weinberger DR (2006) Neuroimaging
      genetic paradigms: a new approach to investigate the pathophysiology and
      treatment of cognitive deficits in schizophrenia. Harv Rev Psychiatry 14:78-91]
      for neuroimaging, and develop the argument that the ethics issues parallel the
      heightened discriminative and cumulative power of imaging genetics. In the new
      combined space, features of discriminative power concern better differentiation
      of disease, sometimes by ethnicity, and incidental findings. Clinical utility,
      prediction and intervention, and stigma and labeling reflect a common ground
      between discriminative and cumulative power. Privacy, autonomy, response
      sensitivity and attitudes, resource allocation for research and for health care,
      and commercialization, are features of cumulative power. Parallel to the clinical
      features highlighted in the Roffman et al. map, the combined space yields
      additional neuroethics features. These are characterized by new knowledge and new
      implications for health care, justice, and policy. We conclude by examining these
      features in the context of public health at the interface of emerging new
      neurotechnologies.

PMID- 19409221
TI  - Distribution and progression of amyloid-beta deposits in the amygdala of the aged
      macaque monkey, and parallels with zinc distribution.
AB  - In this study, we have mapped amyloid beta (Abeta) deposition in the amygdala of
      five aged Japanese monkeys (from 23 to 30 years old). In brief, the aged monkey
      amygdala shows a topographic distribution of Abeta deposits that is subnucleus
      specific and exhibits a distinct temporal progression. The pattern is similar to
      the distribution of Abeta deposits in the human amygdala of Alzheimer's patients
      and of high plaque nondemented cases. The spatial distribution and temporal
      progression were correlated with the distribution of free zinc (Zn), which is
      known to mediate Abeta aggregation. For the basolateral group of subnuclei in
      particular, there is a clear dorsoventral gradient in the progressive
      distribution of Abeta. Abeta depositions first appear in the ventral division of
      the lateral nucleus and parvicellular division of the accessory basal nucleus,
      and then extend into the ventral part of the basal and paralaminar nuclei. All
      these nuclei are also Zn-dense. Conversely, Zn-weak nuclei, which are more
      dorsally situated (i.e. dorsal division of lateral nucleus and magnocellular
      division of basal nucleus) showed only a low level of Abeta deposits, even in
      brains with the greatest Abeta burden. In contrast to the basolateral group, the
      central and medial nuclei and cortical group had Abeta deposits only at later
      stages. In the central and medial nuclei, we identified a lateromedial gradient
      of Abeta deposits, again similar to the gradient of Zn-distribution. In the
      cortical group, Abeta deposits are densest in the deep layer, where Zn is also
      densest. Thus, we suggest the macaque amygdala, with its clear topographic
      distribution of Abeta deposits, may be an effective model for examining the
      complex mechanisms of vulnerability to Abeta deposits. A primate model would be
      advantageous for experimental interventions geared toward therapeutic protection
      from Alzheimer's disease, including by microarray analysis and genetic
      manipulation.

PMID- 19409219
TI  - Chronic unpredictable stress augments +3,4-methylenedioxymethamphetamine-induced
      monoamine depletions: the role of corticosterone.
AB  - Exposure to stress alters the behavioral and neurochemical effects of drugs of
      abuse. However, it is unknown if chronic stress can affect the serotonergic
      depletions induced by the psychostimulant drug 3,4-methylenedioxymethamphetamine
      (MDMA). Rats were exposed to 10 days of chronic unpredictable stress (CUS) which
      resulted in the predicted elevation of basal plasma corticosterone
      concentrations. On the 11th day, rats received four challenge doses of MDMA (5
      mg/kg every 2 h, i.p.) or saline. Five days later, rats were killed and serotonin
      (5-HT) and dopamine content were measured in the striatum, hippocampus, and
      frontal cortex. MDMA produced greater depletions of 5-HT in all three brain
      regions of rats pre-exposed to CUS compared to rats not exposed to CUS. CUS
      exposed rats also had an augmented acute hyperthermic response but a similar
      increase in plasma corticosterone after challenge injections of MDMA compared
      with non-stressed rats similarly challenged with MDMA. Moreover, CUS-exposed rats
      exhibited an MDMA-induced depletion of striatal dopamine that was absent in non
      stressed rats that received MDMA. To investigate the role of corticosterone in
      these effects, the corticosterone synthesis inhibitor, metyrapone (50 mg/kg
      i.p.), was administered prior to each stressor on each of the 10 days of CUS.
      Metyrapone blocked the chronic stress-induced elevation in basal plasma
      corticosterone, prevented the enhancement of MDMA-induced hyperthermia, and
      blocked the enhanced depletions of 5-HT and dopamine in CUS-exposed rats, but had
      no effect on the acute MDMA-induced increases in plasma corticosterone. These
      findings suggest that CUS alone can increase the basal level of corticosterone
      that in turn, plays an important role in enhancing the sensitivity of both 5-HT
      and dopamine terminals to the hyperthermic and monoamine depleting effects of
      MDMA without altering the acute corticosterone response to an MDMA challenge.

PMID- 19409222
TI  - Ultra-low dose naloxone restores the antinociceptive effect of morphine in
      pertussis toxin-treated rats and prevents glutamate transporter downregulation by
      suppressing the p38 mitogen-activated protein kinase signaling pathway.
AB  - We previously demonstrated that ultra-low dose naloxone restores the
      antinociceptive effect of morphine in rats with pertussis toxin (PTX)-induced
      thermal hyperalgesia by reversing the downregulation of glutamate transporter
      (GT) expression and suppressing spinal neuroinflammation. In the present study,
      we examined the underlying mechanisms of this anti-inflammatory effect in PTX
      treated rats, particularly on the expression of GTs. Male Wistar rats were
      implanted with an intrathecal catheter and, in some cases, with a microdialysis
      probe. All rats were injected intrathecally with saline (5 microl) or PTX (1
      microg), then, 4 days later, were randomly assigned to receive a single injection
      of saline, ultra-low dose naloxone (15 ng), or the p38 mitogen-activated protein
      kinase (MAPK) inhibitor SB203580 (5 microg), followed by morphine injection (10
      microg) 30 min later. Our results showed that PTX injection induced activation of
      microglia and a significant increase in P-p38 MAPK expression in the spinal cord.
      Ultra-low dose naloxone plus morphine significantly inhibited the effect of PTX
      on P-p38 MAPK expression in the spinal cord, while the p38 MAPK inhibitor
      SB203580 attenuated the PTX-induced mechanical allodynia, thermal hyperalgesia,
      increase in spinal cerebrospinal fluid excitatory amino acids, and downregulation
      of GTs. These results show that the restoration of the antinociceptive effect of
      morphine and GT expression in PTX-treated rats by ultra-low dose naloxone
      involves suppression of the p38 MAPK signal transduction cascade.

PMID- 19409223
TI  - Imaging the impact of genes on Parkinson's disease.
AB  - Although Parkinson's disease (PD) has traditionally been considered to be a non
      genetic disorder, recent progress in the neurogenetics of PD provided converging
      evidence that genetic factors play a relevant role in the etiology of PD. The
      strongest case for a genetic contribution to PD was made by the discovery of
      mutations in single genes that can cause autosomal dominant (alpha-synuclein
      (SNCA)) and leucine rich repeat kinase 2 (LRRK2) gene) or recessive (Parkin, PTEN
      induced putative kinase 1 (PINK1), DJ-1, and ATP13A2 gene) forms of PD. Here, we
      review how structural and functional neuroimaging of individuals carrying a
      mutation in one of the PD genes has offered a unique avenue of research into the
      pathogenesis of PD. In symptomatic mutation carriers (i.e. those with overt
      disease), brain mapping can help to link the molecular pathogenesis of PD more
      directly with functional and structural changes in the intact human brain. In
      addition, neuroimaging of presymptomatic (i.e. non-manifesting) mutation carriers
      has emerged as a valuable tool to identify mechanisms of adaptive motor
      reorganization at the preclinical stage that may prevent or delay clinical
      manifestation. In addition to mutations causing monogenic forms of PD, common
      polymorphisms in genes that influence mono-aminergic signaling or synaptic
      plasticity may have modifying effects on distinct aspects of PD. We also discuss
      how functional and structural neuroimaging can be used to better characterize
      these genotype-phenotype correlations.

PMID- 19409225
TI  - Excitability and gap junction-mediated mechanisms in nucleus accumbens regulate
      self-stimulation reward in rats.
AB  - The nucleus accumbens (Acb) is a part of the striatum which integrates
      information from cortical and limbic brain structures, and mediates behaviors
      which reinforce reward. Previous work has suggested that neuronal synchrony
      mediated by gap junctions in Acb-related areas is involved in brain pleasure and
      reward. In order to gain insight into functional aspects of the neural
      information processing at the level of the striatum, we explored the possible
      role of Acb gap junctional communication and chemical synapses on reward self
      stimulation in rats using positive reinforcement. Rats were trained to press a
      lever that caused an electrical current to be delivered into the hypothalamus,
      which is recognized to cause pleasure/reward. Intracerebral infusion into the Acb
      of the gap junctional blocker carbenoxolone (CBX) decreased the lever-pressing
      activity. Considering that the net effect of blocking gap junctions is a reduced
      synchronized output of the cellular activities, which at some level represents a
      decrease in excitability, two other inhibitors of neuronal excitability,
      carbamazepine (CBZ) and tetrodotoxin (TTX), were infused into the Acb and their
      effects on lever-pressing assessed. All manipulations that diminished
      excitability in the Acb resulted in reduced lever-pressing activity. CBX and TTX
      were also infused into motor cortex mediating forelimb lever-pressing with no
      effect. However, a manipulation that has the net effect of increasing excitation,
      the infusion of the opiate antagonist naloxone, also decreased significantly
      brain self-stimulation. We conclude that reward behaviors depend to a great
      extent on both excitability and gap junction-mediated mechanisms in Acb neuronal
      networks. Thus, the Acb provides a site for the study of pleasure/reward,
      addiction and conscious experience.

PMID- 19409224
TI  - Neuroimaging of response interference in twins concordant or discordant for
      inattention and hyperactivity symptoms.
AB  - Attention deficit hyperactivity disorder (ADHD) is to a large extent influenced
      by genetic factors, but environmental influences are considered important as
      well. To distinguish between functional brain changes underlying primarily
      genetically and environmentally mediated ADHD, we used functional magnetic
      resonance imaging (fMRI) to compare response interference in monozygotic twins
      highly concordant or discordant for attention problems (AP). AP scores were
      assessed longitudinally with the Child Behavior Check List attention problem
      scale (CBCL-AP). Response interference was measured during two executive function
      paradigms; a color-word Stroop and a flanker task. The neuroimaging results
      indicated that, across the entire sample, children with high CBCL-AP scores,
      relative to children with low CBCL-AP scores, showed decreased activation to
      response interference in dorsolateral prefrontal, parietal and temporal brain
      regions. Increased activation was noted in the premotor cortex and regions
      associated with visual selective attention processing, possibly reflecting
      compensatory mechanisms to maintain task performance. Specific comparisons of
      high and low scoring concordant twin pairs suggest that AP of genetic origin was
      characterized by decreased activation of the left dorsolateral prefrontal cortex
      during the Stroop task and right parietal lobe during the flanker task. In
      contrast, comparison of twins from discordant monozygotic pairs, suggests that AP
      of environmental origin was characterized by decreased activation in left and
      right temporal lobe areas, but only during Stroop interference. The finding of
      distinct brain activation changes to response interference in
      inattention/hyperactivity of "genetic" versus "environmental" origin, indicates
      that genetic and environmental risk factors for attention/hyperactivity problems
      affect the brain in different ways.

PMID- 19409226
TI  - Botulinum toxin type a (150 kDa) decreases exaggerated neurotransmitter release
      from trigeminal ganglion neurons and relieves neuropathy behaviors induced by
      infraorbital nerve constriction.
AB  - Many patients with trigeminal neuropathies suffer severe chronic pain which is
      inadequately alleviated with centrally-acting drugs. These drugs also possess
      severe side effects making compliance difficult. One strategy is to develop new
      treatments without central side effects by targeting peripheral sensory neurons,
      since sensory neuron excitability and neurotransmitter release increase in
      chronic pain states. Such treatments may include the highly purified botulinum
      toxin type A 150 kDa (BoNT/A) which reportedly blocks vesicular neurotransmitter
      release. We set out to determine if experimental trigeminal neuropathy induced by
      infraorbital nerve constriction (IoNC) in rats could alter neurotransmitter
      release from somata of trigeminal sensory neurons and if it could be attenuated
      by BoNT/A. Thus, we monitored the secretory activity of acutely dissociated
      trigeminal ganglion (TRG) neurons from naive and IoNC rats by measuring the
      fluorescence intensity of the membrane-uptake marker (N-(3
      triethylammoniumpropyl)-4-(6-(4-(diethylamino)phenyl)hexatrienyl)pyridinium
      dibromide (FM4-64). FM4-64 staining showed that neurons possess a pool of
      recycled vesicles which could be released by high KCl (75 mM) application. BoNT/A
      pre-treatment of acutely dissociated TRG neurons from naive rats significantly
      reduced the rate of FM4-64 dye release. Neurons isolated from TRG ipsilateral to
      IoNC exhibited significantly faster onset of FM4-64 release than neurons
      contralateral to IoNC (sham surgery). IoNC also produced long-lasting ipsilateral
      tactile allodynia, measured as large decreases of withdrawal thresholds to
      mechanical stimulation. Intradermal injection of BoNT/A in the area of
      infraorbital branch of the trigeminal nerve (IoN) innervation alleviated IoNC
      induced mechanical allodynia and reduced the exaggerated FM4-64 release in TRG
      neurons from these rats. Our results suggest that BoNT/A decreases neuropathic
      pain behaviors by decreasing the exaggerated neurotransmitter release from TRG
      sensory neurons.

PMID- 19409228
TI  - Voltage-dependent calcium signaling in rat cerebellar unipolar brush cells.
AB  - Unipolar brush cells (UBCs) are a class of excitatory interneuron found in the
      granule cell layer of the vestibulocerebellum. Mossy fibers form excitatory
      inputs on to the paint brush shaped dendrioles in the form of giant,
      glutamatergic synapses, activation of which results in prolonged bursts of action
      potentials in the postsynaptic UBC. The axons of UBCs themselves form mossy fiber
      contacts with other UBCs and granule cells, forming an excitatory, intrinsic
      cerebellar network that has the capacity to synchronize and amplify mossy fiber
      inputs to potentially large populations of granule cells. In this paper, we
      demonstrate that UBCs in rat cerebellar slices express low voltage activated
      (LVA) fast-inactivating and high voltage activated (HVA) slowly inactivating
      calcium channels. LVA calcium currents are mediated by T-type calcium channels
      and they are associated with calcium increases in the dendrites and to a lesser
      extent the cell soma. HVA currents, mediated by L-type calcium channels, are
      slowly inactivating and they produce larger overall increases in intracellular
      calcium but with a similar distribution pattern. We review these observations
      alongside several recent papers that examine how intrinsic membrane properties
      influence UBCs firing patterns and we discuss how UBC signaling may affect
      downstream cerebellar processing.

PMID- 19409229
TI  - Timing in the cerebellum: oscillations and resonance in the granular layer.
AB  - The brain generates many rhythmic activities, and the olivo-cerebellar system is
      not an exception. In recent years, the cerebellum has revealed activities ranging
      from low frequency to very high-frequency oscillations. These rhythms depend on
      the brain functional state and are typical of certain circuit sections or
      specific neurons. Interestingly, the granular layer, which gates sensorimotor and
      cognitive signals to the cerebellar cortex, can also sustain low frequency (7-25
      Hz) and perhaps higher-frequency oscillations. In this review we have considered
      (i) how these oscillations are generated in the granular layer network depending
      on intrinsic electroresponsiveness and circuit connections, (ii) how these
      oscillations are correlated with those in other cerebellar circuit sections, and
      (iii) how the oscillating cerebellum communicates with extracerebellar
      structures. It is suggested that the granular layer can generate oscillations
      that integrate well with those generated in the inferior olive, in deep
      cerebellar nuclei and in Purkinje cells. These rhythms, in turn, might play a
      role in cognition and memory consolidation by interacting with the mechanisms of
      long-term synaptic plasticity.

PMID- 19409227
TI  - Dopaminergic projections to the medial preoptic area of postpartum rats.
AB  - Dopamine receptor activity in the rodent medial preoptic area (mPOA) is crucial
      for the display of maternal behaviors, as well as numerous other physiological
      and behavioral functions. However, the origin of dopaminergic input to the mPOA
      has not been identified through neuroanatomical tracing. To accomplish this, the
      retrograde tracer Fluorogold was iontophoretically applied to the mPOA of
      postpartum laboratory rats, and dual-label immunocytochemistry for Fluorogold and
      tyrosine hydroxylase later performed to identify dopaminergic cells of the
      forebrain and midbrain projecting to the mPOA. Results indicate that the number
      of dopaminergic cells projecting to the mPOA is moderate ( approximately 90 cells
      to one hemisphere), and that these cells have an unexpectedly wide distribution.
      Even so, more than half of the dual-labeled cells were found in either what has
      been considered extensions of the A10 dopamine group (particularly the
      ventrocaudal posterior hypothalamus and adjacent medial supramammillary nucleus),
      or in the A10 group of the ventral tegmental area. The rostral hypothalamus and
      surrounding region also contained numerous dual-labeled cells, with the greatest
      number found within the mPOA itself (including in the anteroventral preoptic area
      and preoptic periventricular nucleus). Notably, dual-labeled cells were rare in
      the zona incerta (A13), a site previously suggested to provide dopaminergic input
      to the mPOA. This study is the first to use anatomical tracing to detail the
      dopaminergic projections to the mPOA in the laboratory rat, and indicates that
      much of this projection originates more caudally than previously suggested.

PMID- 19409232
TI  - Apolipoprotein E-genotype dependent hippocampal and cortical responses to
      traumatic brain injury.
AB  - The different alleles of the apolipoprotein E gene (APOE-gene, ApoE-protein) have
      been reported to influence recovery after traumatic brain injury (TBI) in both
      human patients and animal models, with the e4 allele typically conferring poorer
      prognosis for recovery. How the E4 allele, and consequently the ApoE4 isoform,
      affects recovery is unknown, but proposed mechanisms include neurogenesis,
      inflammatory response and amyloid processing or metabolism. Using the controlled
      cortical impact (CCI) model of brain injury and microarray technology we have
      characterized the genomic response to injury in the brains of APOE2, APOE3 and
      APOE4 transgenic mice and identified quantitatively and qualitatively
      significantly different profiles of gene expression in both the hippocampus and
      the cortex of the APOE3 mice compared to APOE4. The observed gene regulation
      predicts functional consequences including effects on inflammatory processes,
      cell growth and proliferation, and cellular signaling, and may suggest that the
      poor recovery post-TBI in APOE4 animals and human patients is less likely to
      result from a specific activation of neurodegenerative mechanisms than a loss of
      reparative capability.

PMID- 19409231
TI  - Depolarization-induced slow current in cerebellar Purkinje cells does not require
      metabotropic glutamate receptor 1.
AB  - Activation of cerebellar Purkinje cells by either brief depolarizing steps or
      bursts of climbing fiber synaptic activation evokes a slow inward current, which
      we have previously called depolarization-induced slow current or DISC. DISC is
      triggered by Ca influx via voltage-sensitive Ca channels and is attenuated by
      inhibitors of vacuolar ATPase or vesicle fusion. This led us to suggest that DISC
      required vesicular release of glutamate from the somatodendritic region of
      Purkinje cells. Furthermore, we found that DISC was attenuated by the mGluR1
      antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester
      (CPCCOEt), indicating that DISC required autocrine activation of metabotropic
      glutamate receptor 1 (mGluR1). Here, we have revisited the role of mGluR1 and
      found that it is, in fact, not required for DISC. CPCCOEt, but not three other
      specific mGluR1 antagonists (JNJ16259685, alpha-amino-5-carboxy-3-methyl-2
      thiopheneacetic acid (3-MATIDA), Bay 36-7620), attenuated DISC, even though all
      four of these drugs produced near-complete blockade of current evoked by puffs of
      the exogenous mGluR1/5 agonist DHPG. Cerebellar slices derived from mGluR1 null
      mice showed substantial DISC that was still attenuated by CPCCOEt. mGluR5 is
      functionally similar to mGluR1, but is not expressed at high levels in cerebellar
      Purkinje cells. 2-Methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), an
      mGluR5 antagonist, did not attenuate DISC, and DISC was still present in Purkinje
      cells derived from mGluR1/mGluR5 double null mice. Thus, neither mGluR1 nor
      mGluR5 is required for DISC in cerebellar Purkinje cells.

PMID- 19409233
TI  - Current advances in lesion-symptom mapping of the human cerebellum.
AB  - While high-resolution structural magnetic resonance imaging (MRI) combined with
      newer analysis methods has become a powerful tool in human cerebral lesion
      studies, comparatively few studies have used these advanced imaging techniques to
      study lesions of the human cerebellum and their associated symptoms. This review
      will summarize the methodology of MRI-based lesion-symptom mapping of the human
      cerebellum and discuss its potential for gaining insights into cerebellar
      function. The investigation of patients with defined focal lesions yields the
      greatest potential for obtaining meaningful correlations between lesion site and
      behavioral deficits. In smaller groups of patients overlay plots and subtraction
      analysis are good options. If larger groups of patients are available, different
      statistical techniques have been introduced to compare behavior and lesion site
      on a voxel-by-voxel basis. Although localization in degenerative cerebellar
      disorders is less accurate because of the diffuse nature of the disease, certain
      information about the supposed function of larger subdivisions of the cerebellum
      can be gained. Examples are given which show that lesion-symptom mapping allows
      to investigate the function of the intermediate zone and cerebellar nuclei. We
      conclude that meaningful correlations between lesion site and behavioral data can
      be obtained in patients with degenerative as well as focal cerebellar disorders.

PMID- 19409234
TI  - The role of the cerebellum in classical conditioning of discrete behavioral
      responses.
AB  - The cerebellum and its associated circuitry constitutes the entire essential
      neuronal system for classical conditioning of eye-blink and other discrete
      responses (e.g. limb flexion) learned with an aversive unconditioned stimulus
      (US) using the standard delay paradigm where the conditioned stimulus (CS) and
      the US coterminate. Evidence reviewed here strongly supports the following
      conclusions. The CS pathway involves sensory relay nuclei projections to the
      pontine nuclei and its mossy fiber projections to the cerebellar cortex and
      nuclei. The US pathway involves activation of the inferior olive (dorsal
      accessory olive for eye blink) and its climbing fiber projections to the
      cerebellar cortex and nuclei. The conditioned response (CR) pathway involves the
      cerebellar interpositus nucleus, the superior cerebellar peduncle pathway to the
      magnocellular red nucleus and rubral projections to premotor and motor nuclei
      generating the behavioral response. Anatomical data, neuronal unit recordings,
      electrical stimulation, lesions and methods of reversible inactivation all
      strongly support the hypothesis that the essential memory trace for the learning
      of these discrete conditioned responses is formed and stored in the cerebellar
      interpositus nucleus. Neuronal/synaptic plasticity is also established in the
      cerebellar cortex in this form of learning but the role of the cortex is less
      clear. We argue that the cortex plays a key role in normal acquisition and
      adaptive timing of the conditioned response, under certain circumstances, but it
      remains unclear exactly what features of conditioning are being encoded in the
      cerebellar cortex in this basic form of associative learning and memory.

PMID- 19409230
TI  - Magnetic resonance imaging of Huntington's disease: preparing for clinical
      trials.
AB  - The known genetic mutation causing Huntington's disease (HD) makes this disease
      an important model to study links between gene and brain function. An autosomal
      dominant family history and the availability of a sensitive and specific genetic
      test allow pre-clinical diagnosis many years before the onset of any typical
      clinical signs. This review summarizes recent magnetic resonance imaging (MRI)
      based findings in HD with a focus on the requirements if imaging is to be used in
      treatment trials. Despite its monogenetic cause, HD presents with a range of
      clinical manifestations, not explained by variation in the number of CAG repeats
      in the affected population. Neuroimaging studies have revealed a complex pattern
      of structural and functional changes affecting widespread cortical and
      subcortical regions far beyond the confines of the striatal degeneration that
      characterizes this disorder. Besides striatal dysfunction, functional imaging
      studies have reported a variable pattern of increased and decreased activation in
      cortical regions in both pre-clinical and clinically manifest HD-gene mutation
      carriers. Beyond regional brain activation changes, evidence from functional and
      diffusion-weighted MRI further suggests disrupted connectivity between
      corticocortical and corticostriatal areas. However, substantial inconsistencies
      with respect to structural and functional changes have been reported in a number
      of studies. Possible explanations include methodological factors and differences
      in study samples. There may also be biological explanations but these are poorly
      characterized and understood at present. Additional insights into this phenotypic
      variability derived from study of mouse models are presented to explore this
      phenomenon.

PMID- 19409236
TI  - [Violence and the young].

PMID- 19409237
TI  - [The Spanish version of the Newcastle Asthma Knowledge Questionnaire for parents
      of children with asthma (NAKQ). Transcultural adaptation and reliability
      analysis].
AB  - INTRODUCTION: The Newcastle Asthma Knowledge Questionnaire for parents of
      children with asthma (NAKQ) has proven to be a valid instrument for asthma
      knowledge assessment of patients and their parents. The widespread use of the SRS
      22 in non-English-speaking countries requires its transcultural adaptation. Our
      objective was to obtain a version of the NAKQ questionnaire adapted to Spanish
      and to analyze its validity and reliability. MATERIAL AND METHODS: The Spanish
      version was obtained by using the forward/back-translation method with expert,
      bilingual translators. The questionnaire was administered to 157 parents with
      high knowledge (n = 78) and low knowledge (n = 79) of asthma. The differences in
      the number of answers between both groups were analyzed with the chi(2) test.
      Internal consistency was determined with Cronbach's alpha coefficient and test
      retest reliability with the tau-b of Kendall correlation coefficient, and kappa
      statistics. RESULTS: At the end of the process, 23 of the 31 items were
      classified as of total equivalence and eight ase of moderate equivalence. The
      mean score of parents high knowledge was 23 +/- 2.94 and the mean score of
      parents low knowledge was 16.84 +/- 2.56. The difference between the two groups
      was statistically significant (p < 0.001). The overall Cronbach's alpha
      coefficient of the questionnaire was 0.72, the Kendall's tau-b 0,8573 was
      significant (p = 0.01) and the kappa index showed good or very good consistency
      in more than half of the items. CONCLUSIONS: The Spanish version of the NAKQ has
      proven to be acceptable and culturally equivalent to the original version and it
      has a good degree of consistency, validity and reliability.

PMID- 19409239
TI  - [Chylothorax: experience in a paediatric intensive care unit].
AB  - INTRODUCTION: Chylothorax is a fairly common condition seen in paediatric
      intensive care units, since it usually appears in the postoperative care of
      cardiothoracic surgery. Nevertheless, there is still uncertainty on the most
      effective treatment option and the prognostic factors for a positive response.
      OBJECTIVES: To describe our experience in the management of patients with
      chylothorax admitted to our paediatric intensive care unit (PICU). To look for
      prognostic factors for a response to the different treatments. MATERIAL AND
      METHOD: This is a descriptive and analytical, retrospective study, that includes
      the period 2000-2007. All cases of chylothorax of any aetiology diagnosed during
      this period in our PICU were included (excluding congenital neonatal cases).
      Demographic variables, aetiology, evolution of the debit, complications, type of
      treatment with results and side effects were recorded, along with the clinical
      progress. The possible relationship between the different variables (age,
      aetiology, debit), and progress, as well as response to treatments was analysed.
      RESULTS: A total of 24 patients, 12 males and 12 females, were included, of which
      70.8% (17) were under 1 year of age. A total of 79.2% (19) were in postoperative
      care after surgery for a congenital heart disease. The most notable complications
      were sepsis (3/24 cases, 12.5%), hypoalbuminaemia (3/24, 12.5%), haemodynamic
      changes (2/24, 8.3%) and catheter-associated sepsis (2/16, 12.5%). The treatment
      with fat-free or rich in medium chain triglycerides diet was effective in 9/21
      cases (43%) and total parenteral nutrition in 3/5 (60%), as opposed to the
      infusion of somatostatin in 8/11 (73%), used in second or third line.
      Somatostatin side effects were hypoglycaemia, hyperglycaemia and digestive
      disturbances, one patient in each case, and not causing complications. We did not
      find prognostic factors as regards progression or for the response to the
      different treatments. CONCLUSIONS: Sepsis, hypoalbuminaemia and haemodynamic
      disturbances were found to be complications associated to chylothorax. The
      treatment with somatostatin did not produce severe side effects, and there was a
      positive response in 73% of those treated with it.

PMID- 19409238
TI  - [The assessment of sedation in the critically ill child on mechanical ventilation
      during tracheal suction].
AB  - OBJECTIVES: To compare the changes in clinical sedation scales, bispectral index
      (BIS) and physiological variables occurring during tracheal suction in critically
      ill children. DESIGN: Prospective, observational study in critically ill children
      on mechanical ventilation. BIS value, heart rate (HR), systolic blood pressure
      (SPB), diastolic blood pressure (DBP), modified Ramsay sedation scale score and
      the dose of sedative drugs were recorded before and 3 minutes after every
      tracheal suction. RESULTS: A total of 83 tracheal suctions were analyzed from 46
      children, 1 month to 15 years of age. Most of the children (92%) were receiving
      continuous infusions of fentanyl and midazolam, and 45.7% of them were receiving
      vecuronium. The increase in BIS, SPB and DBP values were small but statistically
      significant (BIS, from 51.8 to 57.3; SBP, from 92.9 to 103.1 mmHg; DBP, from 51.8
      to 58.9 mmHg). There was poor correlation between the BIS, HR, SBP and DBP values
      before and after suction. A total of 87% of patients maintained the same Ramsay
      score values. CONCLUSIONS: Tracheal suction produces a slight increase in the BIS
      and the BP in critically ill children who are receiving sedation by continuous
      infusion. Most children with adequate sedation do not need any other drugs before
      the tracheal suction. Physiological variables have no correlation with sedation
      scales or BIS values during the tracheal suction.

PMID- 19409240
TI  - [Presence of parents in the emergency room during invasive procedures: do they
      prefer to be present?].
AB  - INTRODUCTION: Parents are not usually present during procedures in the paediatric
      emergency room (ER), although an increasing number of them would like to. Our
      goal was to find out how parents felt about them being present in ER during
      procedures. MATERIAL AND METHODS: This is an observational study. Questionnaires
      were distributed among parents of patients in the ER during January and February
      2007. Data included demographic questions as well as the opinion regarding their
      preference on being present during venipuncture, stitching, lumbar puncture or
      cardiopulmonary resuscitation. They were also asked about who should take the
      decision whether to allow the family to be present or not. RESULTS: A total of 98
      questionnaires were analyzed. The median age of participants was 32 years-old, of
      which 84.5% would prefer to be present for venipuncture, 70.4% for stitching,
      66.3% for lumbar puncture and 61.2% for cardiopulmonary resuscitation.
      Venipuncture was performed on 21% of the children, stitching on 4%, and lumbar
      puncture on 2%. There was no cardiopulmonary resuscitation. Parents considered
      that the decision about being present should be taken by the professional in 74%
      (venipuncture), 75% (stitching), 80% (lumbar puncture) and 81% (cardiopulmonary
      resuscitation). The mean age of the group that preferred to be present was lower
      (32 vs. 40 years; p = 0.039). CONCLUSIONS: Most parents surveyed preferred to be
      present during invasive procedures in ER. The more invasive the procedure is the
      higher reluctance from parents to be present. Most parents thought the decision
      should be taken by the health care professional, particularly when the procedure
      is more invasive.

PMID- 19409241
TI  - [Final size attained in type 1 diabetes children].
AB  - OBJECTIVE: To describe the final height and height-gain in relation to target
      height, in children with type 1 diabetes mellitus, and analyse their relationship
      to different variables. PATIENTS AND METHODS: Retrospective analysis of the
      growth data of 52 children (27 girls) diagnosed with type 1 diabetes mellitus
      before 14 years old, and followed up until their final height was attained. MAIN
      VARIABLES: final height, target height, illness duration, glycated haemoglobin
      (HbA1c), insulin dose, BMI, and other autoimmune diseases. RESULTS: The height
      SDS (standard deviation scale) at diagnosis was slightly higher (0.734 in boys
      and 0.563 in girls). During the development of the disease, a growth reduction
      was seen, which was significantly higher in boys of prepubertal age (p = 0.016).
      The mean final height attained was 173.14 +/- 5.28 cm in boys and 161.9 +/- 6.97
      cm in girls. Height gain was 1.56 +/- 3.66 in boys (SDS = -0.034) and 2.26 +/-
      6.13 in girls (SDS = 0.385). The only variable significantly related to height
      gain was mean glycated-haemoglobin (growth reduction of 2 cm for every increment
      of 1% in mean glycated-haemoglobin). CONCLUSIONS: At onset, diabetic children
      were slightly taller than the general population. A growth reduction was shown as
      the disease developed, significantly higher in boys of prepubertal age. The final
      height in boys was slightly lower than the mean, but in girls was similar to the
      general population. Both sexes attained their target height, although the height
      gain was less in boys. Poorer metabolic control was associated with reduced
      height gain.

PMID- 19409242
TI  - [Influence of socioeconomic factors on weight, length and head circumference
      measurements in newborns from 35 to 42 weeks gestational age].
AB  - BACKGROUND AND OBJECTIVE: gestational age and anthropometric measurements, i.e.
      weight, length and head circumference at birth, have all been used as predictors
      of neonatal morbidity-mortality and adult morbidity. Differences in ethnic or
      socioeconomic background of newborn cohorts, as well as methodological
      differences between studies limit the validity and application of current
      anthropometric curves across different populations. Thus, we conducted a study to
      obtain local reference data in a Hospital that had a medium-high socio-economic
      class population, probably different to others recently published in our
      geographic area, and to compare them. PATIENTS AND METHOD: Weight, length and
      head circumference at birth were retrospectively analysed in 31,397 live
      Caucasian neonates born at 23-42 weeks in SCIAS-Hospital de Barcelona between
      1992 and 2006. Only single gestations were selected and no other exclusion by
      materno-fetal or neonatal pathology criteria were applied. Percentile values,
      mean and standard deviation for each anthropometric measurement were calculated
      according to gestational age and gender. They were compared with the results from
      recent publications of our geographic area. RESULTS: Males were found to have
      significantly higher weight, length and head circumference values than females
      from 36 weeks. There was a trend towards higher values in our population when
      compared with others in our geographic area. CONCLUSIONS: The influence of
      socioeconomic factors on fetal growth seems evident. Nevertheless, it is
      difficult to assume that the observed differences must be exclusively due to the
      population characteristics or the different methodologies in the selection of the
      sample. Thus, it is desirable to have anthropometric reference curves obtained
      from populations of surrounding areas, with epidemiological methodologies that
      might be more appropriate in identifying valid outcome predictors, and enable us
      to compare with others groups according to racial, socioeconomic and disease
      factors.

PMID- 19409243
TI  - [Eating habits in children under 2 years old according to ethnic origin in a
      Barcelona urban area].
AB  - INTRODUCTION: The importance of the influence of diet in the first few years of
      life on child growth and development and its relationship with the prevention of
      chronic diseases in childhood and adulthood has recently been stressed. The aim
      of the present study was to determine the presence or absence of inappropriate
      feeding practices, defined as non-compliance with dietary recommendations, in
      children aged less than 2 years old through a survey. SUBJECTS AND METHODS: The
      parents of 462 children were administered a 14-item questionnaire on compliance
      with dietary recommendations to define nutritional risk. Depending on the
      parents' country of birth, children were classified as autochthonous, gypsy, or
      non-autochthonous. RESULTS: In absolute results, high percentages of non
      compliance with a substantial number of recommendations were found in all
      children and in each of the three groups, with the consequent danger of
      nutritional risk. CONCLUSIONS: In children in our environment, there are numerous
      inadequate feeding practices that constitute nutritional risk factors and require
      preventive and educational interventions to improve the future health of these
      children when they reach adulthood. In children from ethnic groups, no
      particularly severe inadequate feeding practices related to origin were found.
      The gypsy ethnic group requires additional nutritional health education
      interventions. Health workers should improve the information provided on
      nutritional recommendations and feeding practices to avoid misunderstanding, as
      in the case of gluten.

PMID- 19409245
TI  - [Flexural psoriasis induced by infliximab and adalimumab in a patient with
      Crohn's disease].
AB  - Anti-TNF drugs are used increasingly in several diseases with immune-mediated
      inflammation, not only in rheumatological conditions, but also in inflammatory
      bowel disease and psoriasis. Different side effects have been described over the
      last few years, including the development of psoriasis or psoriasiform
      exanthemas. These drugs began to be used in paediatrics during the 90's,
      therefore paediatricians need to be aware of the adverse effects that may occur.
      We describe here a flexural psoriasis induced by both infliximab and adalimumab
      in a paediatric patient with Crohn's Disease. To the best of our knowledge, this
      is the first reported paediatric case of psoriasis triggered by an anti-TNF drug,
      as well as the first case of psoriasis induced by adalimumab in patients with
      inflammatory bowel disease.

PMID- 19409244
TI  - [Response to stopping azathioprine in Crohn's patients on combined treatment with
      infliximab].
AB  - BACKGROUND: The use of immunomodulatory agents has changed the management of
      inflammatory bowel disease. Immunosuppressive drugs (mainly thiopurines) and
      biological treatments (mainly monoclonal antibodies against TNFalpha) are
      currently most frequently and earlier used. The recent report of new cases of the
      rare and almost always fatal hepatosplenic T-cell lymphoma in young patients on
      combined therapy with azathioprine/6-mercaptopurine and infliximab suggests that
      the optimal strategies for reducing increased risk of side-effects need to be
      urgently assessed. PATIENTS AND METHOD: We report the effects of stopping
      immunosupressants in four Crohn's disease patients previously treated with
      azathioprine and infliximab for 6-12 months as combined therapy. The appearance
      of infusion reactions due to immunogenicity and the loss of efficacy of
      infliximab are evaluated. RESULTS: No adverse events attributable to
      immunosuppression cessation or changes in infliximab efficacy have been noted
      during a 6-month evaluation period. CONCLUSIONS: Stopping immunosuppressant
      therapy in Crohn's patients with a previous good response to combination therapy
      (azathioprine and infliximab) does not result in an increased risk of adverse
      events or loss of infliximab efficacy. Our results must be confirmed in larger
      and longer studies. Until the pathogenic role of this combined therapy in the
      incidence of hepatosplenic T-cell lymphoma is clearly defined, we consider that
      monotherapy with infliximab after a period on combined treatment is a safe and
      effective strategy.

PMID- 19409247
TI  - [The clinical spectrum of cutaneous neonatal lupus erythematosus].
AB  - BACKGROUND: Neonatal lupus erythematosus (NLE) is an uncommon disease described
      mainly through isolated case reports and a few published series. OBJECTIVE: To
      examine the clinical and serological spectrum, and course of the disease in
      neonates with NLE and cutaneous involvement. METHODS: A retrospective study was
      performed that included all children with NLE that came to the Dermatology
      Department between 1995 and 2006. RESULTS: Eight children with a diagnosis of NLE
      with cutaneous involvement were identified, with a male:female ratio of 3:1. Anti
      Ro antibodies were found in all cases and no cases with anti-RNP antibodies were
      found. Facial lesions were observed in all cases and in 7 cases the skin
      eruptions cleared within 4.3 months; the remaining patient was still in follow up
      when the data were collected. The clinical course of patients who were followed
      up was satisfactory. CONCLUSIONS: In our series, NLE was three times more
      frequent in males. Involvement of sun-exposed areas, such as the face with
      annular lesions was the most common finding. We found one case of NLE with
      cutaneous involvement and persistent ductus arteriosus. Anti-Ro antibodies were
      found in all cases and skin eruptions cleared by 7 months of age, concurrent with
      the waning of the maternally derived antibodies. Four of the mothers were
      asymptomatic and unaware of their condition, emphasizing the importance of
      following up these patients due to the possibility of developing an autoimmune
      disease.

PMID- 19409246
TI  - [Pediatric intensive care after brain tumor surgery].
AB  - INTRODUCTION: Primary brain tumors are the most common solid tumors in children.
      Surgery is the basis of treatment for these patients, who require postoperative
      admission to the ICU-P. The aim of this study was to at the epidemiology of brain
      tumors of patients admitted to our ICU-P and to analyze the progress of these
      children in the postoperative period. PATIENTS AND METHODS: Retrospective
      prospective study of children admitted to our unit after brain tumor surgery
      between January 1998 and January 2007. We collected information such as, personal
      details, clinical characteristics, type of intervention and postoperative period.
      RESULTS: We reviewed 161 postoperative periods, corresponding to 134 patients
      (54.5% male). The mean age was 7 years and 8 months +/- 5 months. The most common
      location was the posterior fossa (44.8%). The most common histological type was
      low grade/intermediate astrocytoma (44.7%). The most frequent complication was
      diabetes insipidus (9.9%). Resection was complete in 58.4% patients. The median
      stay in the ICU-P was 2 days (0-61 days). 3 patients died after surgery.
      CONCLUSIONS: The epidemiology of the group of patients admitted to our ICU-P is
      similar to the general population. The most common complication is diabetes
      insipidus.

PMID- 19409248
TI  - [Parental presence during invasive procedures in the emergency department].
AB  - Over the last decades, health care has been moving away from the paternalistic
      model, to one of family-centered care. In the pediatric emergency department,
      this new trend has led to parents playing a larger role in the health care of
      children, particularly during invasive procedures and/or resuscitation. Despite
      the increased attention to family presence, it remains a controversial topic,
      especially among emergency medical staff. Several studies have been performed
      that look at the advantages and disadvantages of this new way of conceiving child
      health care. To our knowledge, there is only one Spanish article on this topic,
      which is the reason why we performed a literature review on family presence in
      the emergency department.

PMID- 19409249
TI  - [Neonatal withdrawal syndrome due to excessive maternal caffeine intake].

PMID- 19409250
TI  - [Perinatal listeriosis: an emerging infection?].

PMID- 19409251
TI  - [Miller-Dieker syndrome].

PMID- 19409253
TI  - [Streptococcal toxic shock syndrome: an emerging pathology?].

PMID- 19409252
TI  - [Invasive disease due to Campylobacter fetus in an immunocompetent infant].

PMID- 19409254
TI  - [Hypoglossal nerve palsy as a complication of the use of laryngeal mask airway].

PMID- 19409255
TI  - [Eosinophilic cellulitis presenting as cutaneous blistering].

PMID- 19409256
TI  - [A 5 month old infant with immediate anaphylactic hypersensitivity to cow's milk
      proteins contained in a gingival gel].

PMID- 19409257
TI  - [Purpura lesions and alveolar infiltrates: propylthiouracil-induced vasculitis].

PMID- 19409258
TI  - The dawning of primate optogenetics.
AB  - In this issue of Neuron, Han and colleagues bring optogenetic methods into use in
      nonhuman primates by demonstrating the feasibility of achieving cell-type
      specific photoactivation of macaque neocortical neurons. The use of optogenetic
      approaches in nonhuman primates promises to revolutionize our understanding of
      the neural circuitry that mediates complex cognitive functions.

PMID- 19409259
TI  - Deos the bairn not raed ervey lteter by istlef, but the wrod as a wlohe?
AB  - In this issue of Neuron, Glezer et al. find higher sensitivity to changes in real
      words than pseudowords in the left visual word form area (VWFA). Here we discuss
      the implications of their findings and the constraints they impose on neural
      coding in the lVWFA.

PMID- 19409260
TI  - A lethal convergence of dopamine and calcium.
AB  - The controversy about whether dopamine contributes to cell loss in Parkinson's
      disease takes a new turn as Mosharov et al. in this issue of Neuron demonstrate
      that Ca2+ influx through L-type channels elevates dopamine synthesis to
      potentially toxic levels in vulnerable ventral mesencephalon neurons.

PMID- 19409261
TI  - AMPA receptor subunits get their share of the pie.
AB  - Determining the precise subunit composition of AMPARs in situ has been an
      enduring challenge. In this issue of Neuron, Lu et al. make significant headway
      into this pesky problem by using a clever single-cell genetic knockout approach.
      In a Herculean effort, they provide the field with the completeness of a pie
      chart outlining the contribution of each AMPAR subunit to basal synaptic
      transmission at CA1 hippocampus synapses--and we get a pie chart for somatic
      extrasynaptic receptors, too.

PMID- 19409262
TI  - The speed of categorization in the human visual system.
AB  - A new study by Liu et al. in this issue of Neuron looks at how information about
      object category can be extracted from intracerebral recordings from the visual
      cortical areas in epileptic patients. It shows that information about whether the
      object is a face, an animal, a chair, a fruit, or a vehicle is present as early
      as 100 ms after the onset of a stimulus.

PMID- 19409264
TI  - Millisecond-timescale optical control of neural dynamics in the nonhuman primate
      brain.
AB  - To understand how brain states and behaviors are generated by neural circuits, it
      would be useful to be able to perturb precisely the activity of specific cell
      types and pathways in the nonhuman primate nervous system. We used lentivirus to
      target the light-activated cation channel channelrhodopsin-2 (ChR2) specifically
      to excitatory neurons of the macaque frontal cortex. Using a laser-coupled
      optical fiber in conjunction with a recording microelectrode, we showed that
      activation of excitatory neurons resulted in well-timed excitatory and
      suppressive influences on neocortical neural networks. ChR2 was safely expressed,
      and could mediate optical neuromodulation, in primate neocortex over many months.
      These findings highlight a methodology for investigating the causal role of
      specific cell types in nonhuman primate neural computation, cognition, and
      behavior, and open up the possibility of a new generation of ultraprecise
      neurological and psychiatric therapeutics via cell-type-specific optical neural
      control prosthetics.

PMID- 19409265
TI  - Evidence for highly selective neuronal tuning to whole words in the "visual word
      form area".
AB  - Theories of reading have posited the existence of a neural representation coding
      for whole real words (i.e., an orthographic lexicon), but experimental support
      for such a representation has proved elusive. Using fMRI rapid adaptation
      techniques, we provide evidence that the human left ventral occipitotemporal
      cortex (specifically the "visual word form area," VWFA) contains a representation
      based on neurons highly selective for individual real words, in contrast to
      current theories that posit a sublexical representation in the VWFA.

PMID- 19409263
TI  - Rapid neocortical dynamics: cellular and network mechanisms.
AB  - The highly interconnected local and large-scale networks of the neocortical sheet
      rapidly and dynamically modulate their functional connectivity according to
      behavioral demands. This basic operating principle of the neocortex is mediated
      by the continuously changing flow of excitatory and inhibitory synaptic barrages
      that not only control participation of neurons in networks but also define the
      networks themselves. The rapid control of neuronal responsiveness via synaptic
      bombardment is a fundamental property of cortical dynamics that may provide the
      basis of diverse behaviors, including sensory perception, motor integration,
      working memory, and attention.

PMID- 19409266
TI  - Uncoupling dendrite growth and patterning: single-cell knockout analysis of NMDA
      receptor 2B.
AB  - N-methyl-D-aspartate receptors (NMDARs) play important functions in neural
      development. NR2B is the predominant NR2 subunit of NMDAR in the developing
      brain. Here we use mosaic analysis with double markers (MADM) to knock out NR2B
      in isolated single cells and analyze its cell-autonomous function in dendrite
      development. NR2B mutant dentate gyrus granule cells (dGCs) and barrel cortex
      layer 4 spiny stellate cells (bSCs) have similar dendritic growth rates, total
      length, and branch number as control cells. However, mutant dGCs maintain
      supernumerary primary dendrites resulting from a pruning defect. Furthermore,
      while control bSCs restrict dendritic growth to a single barrel, mutant bSCs
      maintain dendritic growth in multiple barrels. Thus, NR2B functions cell
      autonomously to regulate dendrite patterning to ensure that sensory information
      is properly represented in the cortex. Our study also indicates that molecular
      mechanisms that regulate activity-dependent dendrite patterning can be separated
      from those that control general dendrite growth and branching.

PMID- 19409267
TI  - Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes
      selective death of substantia nigra neurons.
AB  - The basis for selective death of specific neuronal populations in
      neurodegenerative diseases remains unclear. Parkinson's disease (PD) is a
      synucleinopathy characterized by a preferential loss of dopaminergic neurons in
      the substantia nigra (SN), whereas neurons of the ventral tegmental area (VTA)
      are spared. Using intracellular patch electrochemistry to directly measure
      cytosolic dopamine (DA(cyt)) in cultured midbrain neurons, we confirm that
      elevated DA(cyt) and its metabolites are neurotoxic and that genetic and
      pharmacological interventions that decrease DA(cyt) provide neuroprotection. L
      DOPA increased DA(cyt) in SN neurons to levels 2- to 3-fold higher than in VTA
      neurons, a response dependent on dihydropyridine-sensitive Ca2+ channels,
      resulting in greater susceptibility of SN neurons to L-DOPA-induced
      neurotoxicity. DA(cyt) was not altered by alpha-synuclein deletion, although
      dopaminergic neurons lacking alpha-synuclein were resistant to L-DOPA-induced
      cell death. Thus, an interaction between Ca2+, DA(cyt), and alpha-synuclein may
      underlie the susceptibility of SN neurons in PD, suggesting multiple therapeutic
      targets.

PMID- 19409269
TI  - Expression of long-term plasticity at individual synapses in hippocampus is
      graded, bidirectional, and mainly presynaptic: optical quantal analysis.
AB  - Key aspects of the expression of long-term potentiation (LTP) and long-term
      depression (LTD) remain unresolved despite decades of investigation. Alterations
      in postsynaptic glutamate receptors are believed to contribute to the expression
      of various forms of LTP and LTD, but the relative importance of presynaptic
      mechanisms is controversial. In addition, while aggregate synaptic input to a
      cell can undergo sequential and graded (incremental) LTP and LTD, it has been
      suggested that individual synapses may only support binary changes between
      initial and modified levels of strength. We have addressed these issues by
      combining electrophysiological methods with two-photon optical quantal analysis
      of plasticity at individual active (non-silent) Schaffer collateral synapses on
      CA1 pyramidal neurons in acute slices of hippocampus from adolescent rats. We
      find that these synapses sustain graded, bidirectional long-term plasticity.
      Remarkably, changes in potency are small and insignificant; long-term plasticity
      at these synapses is expressed overwhelmingly via presynaptic changes in
      reliability of transmitter release.

PMID- 19409268
TI  - Synaptic and extrasynaptic factors governing glutamatergic retinal waves.
AB  - In the few days prior to eye-opening in mice, the excitatory drive underlying
      waves switches from cholinergic to glutamatergic. Here, we describe the unique
      synaptic and spatiotemporal properties of waves generated by the retina's
      glutamatergic circuits. First, knockout mice lacking vesicular glutamate
      transporter type 1 do not have glutamatergic waves, but continue to exhibit
      cholinergic waves, demonstrating that the two wave-generating circuits are
      linked. Second, simultaneous outside-out patch and whole-cell recordings reveal
      that retinal waves are accompanied by transient increases in extrasynaptic
      glutamate, directly demonstrating the existence of glutamate spillover during
      waves. Third, the initiation rate and propagation speed of retinal waves, as
      assayed by calcium imaging, are sensitive to pharmacological manipulations of
      spillover and inhibition, demonstrating a role for both signaling pathways in
      shaping the spatiotemporal properties of glutamatergic retinal waves.

PMID- 19409270
TI  - Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic
      approach.
AB  - The precise subunit composition of synaptic ionotropic receptors in the brain is
      poorly understood. This information is of particular importance with regard to
      AMPA-type glutamate receptors, the multimeric complexes assembled from GluA1-A4
      subunits, as the trafficking of these receptors into and out of synapses is
      proposed to depend upon the subunit composition of the receptor. We report a
      molecular quantification of synaptic AMPA receptors (AMPARs) by employing a
      single-cell genetic approach coupled with electrophysiology in hippocampal CA1
      pyramidal neurons. In contrast to prevailing views, we find that GluA1A2
      heteromers are the dominant AMPARs at CA1 cell synapses (approximately 80%). In
      cells lacking GluA1, -A2, and -A3, synapses are devoid of AMPARs, yet synaptic
      NMDA receptors (NMDARs) and dendritic morphology remain unchanged. These data
      demonstrate a functional dissociation of AMPARs from trafficking of NMDARs and
      neuronal morphogenesis. This study provides a functional quantification of the
      subunit composition of AMPARs in the CNS and suggests novel roles for AMPAR
      subunits in receptor trafficking.

PMID- 19409271
TI  - The orbitofrontal cortex and ventral tegmental area are necessary for learning
      from unexpected outcomes.
AB  - Humans and other animals change their behavior in response to unexpected
      outcomes. The orbitofrontal cortex (OFC) is implicated in such adaptive
      responding, based on evidence from reversal tasks. Yet these tasks confound using
      information about expected outcomes with learning when those expectations are
      violated. OFC is critical for the former function; here we show it is also
      critical for the latter. In a Pavlovian overexpectation task, inactivation of OFC
      prevented learning driven by unexpected outcomes, even when performance was
      assessed later. We propose this reflects a critical contribution of outcome
      signaling by OFC to encoding of reward prediction errors elsewhere. In accord
      with this proposal, we report that signaling of reward predictions by OFC neurons
      was related to signaling of prediction errors by dopamine neurons in ventral
      tegmental area (VTA). Furthermore, bilateral inactivation of VTA or contralateral
      inactivation of VTA and OFC disrupted learning driven by unexpected outcomes.

PMID- 19409274
TI  - Below the convergence.

PMID- 19409275
TI  - Bird head stabilization.

PMID- 19409272
TI  - Timing, timing, timing: fast decoding of object information from intracranial
      field potentials in human visual cortex.
AB  - The difficulty of visual recognition stems from the need to achieve high
      selectivity while maintaining robustness to object transformations within
      hundreds of milliseconds. Theories of visual recognition differ in whether the
      neuronal circuits invoke recurrent feedback connections or not. The timing of
      neurophysiological responses in visual cortex plays a key role in distinguishing
      between bottom-up and top-down theories. Here, we quantified at millisecond
      resolution the amount of visual information conveyed by intracranial field
      potentials from 912 electrodes in 11 human subjects. We could decode object
      category information from human visual cortex in single trials as early as 100 ms
      poststimulus. Decoding performance was robust to depth rotation and scale
      changes. The results suggest that physiological activity in the temporal lobe can
      account for key properties of visual recognition. The fast decoding in single
      trials is compatible with feedforward theories and provides strong constraints
      for computational models of human vision.

PMID- 19409276
TI  - Anolis lizards.

PMID- 19409273
TI  - State-dependent variability of neuronal responses to transcranial magnetic
      stimulation of the visual cortex.
AB  - Electrical brain stimulation is a promising tool for both experimental and
      clinical applications. However, the effects of stimulation on neuronal activity
      are highly variable and poorly understood. To investigate the basis of this
      variability, we performed extracellular recordings in the visual cortex following
      application of transcranial magnetic stimulation (TMS). Our measurements of
      spiking and local field potential activity exhibit two types of response patterns
      which are characterized by the presence or absence of spontaneous discharge
      following stimulation. This variability can be partially explained by state
      dependent effects, in which higher pre-TMS activity predicts larger post-TMS
      responses. These results reveal the possibility that variability in the neural
      response to TMS can be exploited to optimize the effects of stimulation. It is
      conceivable that this feature could be utilized in real time during the treatment
      of clinical disorders.

PMID- 19409277
TI  - Dinosaurs.

PMID- 19409278
TI  - Filling-in afterimage colors between the lines.
AB  - It is known that when a colored surface is viewed for some time and a blank
      screen is presented afterwards, an afterimage can be perceived in the
      complementary color. Color appearances in afterimages are due to adaptation of
      retinal cones and they are especially vivid when contours, presented after the
      adapting image, coincide with the blurred edges of the afterimage [1]. We report
      here that one and the same colored stimulus can induce multiple, differently
      colored afterimages, and that colored afterimages can also be perceived at
      regions that were not adapted to color. The observed filling-in of afterimage
      colors strongly depends on contours presented after the colored stimulus,
      revealing color-contour interactions that resemble filling-in of 'real' colors.

PMID- 19409279
TI  - Group behaviour: leadership by those in need.
AB  - A new model of animal group behaviour shows that, when the need to reach a target
      outweighs the costs of splitting from the group, a minority of the most 'needy'
      individuals become the leaders of large groups.

PMID- 19409280
TI  - Cell division: breaking up is easy to do.
AB  - How did cells divide before protein machines evolved? A new study shows that
      bacteria can reproduce without the division machinery, supporting the idea that
      primordial cells could have divided using physical mechanisms alone.

PMID- 19409281
TI  - Memory networks: answering the call of the hippocampus.
AB  - Without the hippocampus, experiences disappear without a memory trace. A recent
      study shows that changing synaptic strength within the hippocampus alters circuit
      function in widely distributed brain networks.

PMID- 19409282
TI  - DNA repair: a riddle at a double-strand break.
AB  - Ubiquitin is known to accumulate at the sites of DNA damage. The identification
      of a new ubiquitin ligase, RIDDLIN, provides evidence for a ubiquitin-signalling
      cascade that regulates the assembly of an important DNA repair complex at a DNA
      double-strand break.

PMID- 19409283
TI  - Fungal morphogenesis: some like it hot.
AB  - The ability to reversibly convert between budding yeast-like and filamentous
      hyphal forms is important for the virulence of Candida albicans. A new study now
      provides insight into the relationship between environmental temperature and the
      signalling mechanisms that regulate morphogenesis in this fungal pathogen.

PMID- 19409285
TI  - Critical periods: motion sensitivity is early in all areas.
AB  - Recent work shows that global motion sensitivity, a property of extrastriate
      cortex, can be altered by early visual deprivation, while binocularity, a
      property of primary visual cortex, is still plastic. This contradicts the
      hypothesis that critical periods end later at higher levels of the system.

PMID- 19409284
TI  - Organelle division: dynamin-related proteins in apicomplexans.
AB  - Establishing an infection within a host requires efficient invasion and division.
      In the intracellular parasite Toxoplasma gondii, these functions are mediated by
      dynamin-related proteins with a unique evolutionary history.

PMID- 19409286
TI  - Animal navigation: a wake-up call for homing.
AB  - Many animals seem to know their location even when far from home. Evidence
      variously implicates odors or magnetic fields. The most consistent olfactory
      results, however, may not mean what we think.

PMID- 19409287
TI  - Animal evolution: once upon a time.
AB  - The evolutionary relationships between the earliest branches of the animal
      kingdom - bilaterians, cnidarians, ctenophores, sponges and placozoans - are
      contentious. A new phylogenomic analysis suggests a return to old ideas.

PMID- 19409288
TI  - Prominin1 (CD133) as an intestinal stem cell marker: promise and nuance.

PMID- 19409289
TI  - Acute hepatitis C infection in correctional settings.

PMID- 19409290
TI  - Treatment of hyperammonemia in liver failure: a tale of two enzymes.

PMID- 19409291
TI  - Further promise of stem cells therapies in the enteric nervous system.

PMID- 19409293
TI  - Rasch analysis of the Oxford Knee Score.
AB  - OBJECTIVES: Use Rasch analysis to examine the psychometric properties of the
      Oxford Knee Score (OKS), particularly in respect to unidimensionality, and
      consistency of item functioning before and after total knee replacement and
      across age and gender groups. METHODS: The 12-item OKS was administered to 1,712
      patients before the surgery, and 1,322 and 855 patients were administered the
      instrument repeatedly at the 6-month and 2-year postoperative assessments,
      respectively. Data were fitted to the Rasch partial credit model with the
      Winsteps program. Differential item functioning (DIF) analysis was performed, and
      fit statistics in combination with principal components analysis of the residuals
      were used to test the unidimensionality assumption. The fit criteria were set at
      1.5 and 2.0 for infit mean-square (MNSQ) and outfit MNSQ, respectively. RESULTS:
      At baseline, item difficulty ranged from -1.86 to 1.78 logits, and person
      measures had a mean+/-SD of -0.01+/-0.89. Misfit items were "limping" and "night
      pain" in preoperative data and "limping" and "kneeling" in postoperative data.
      After removing items limping and kneeling and recoding item night pain, none of
      the items misfit at each of the time points and there was stability of item
      difficulty ordering across time. In the modified OKS set, five items displayed
      DIF by age and three by gender. CONCLUSION: The original OKS had adequate
      targeting and good coverage of knee severity levels in preoperative patients. The
      modified 10-item OKS data fit the Rasch model and had stable item difficulty
      ordering over time.

PMID- 19409292
TI  - Subchondral fluid dynamics in a model of osteoarthritis: use of dynamic contrast
      enhanced magnetic resonance imaging.
AB  - OBJECTIVE: The hypothesis of this study is that changes in fluid dynamics in
      subchondral bone bear a functional relationship to bone remodeling and cartilage
      breakdown in osteoarthritis (OA). We have utilized dynamic contrast-enhanced
      (DCE) magnetic resonance imaging (MRI) to extract kinetic parameters of bone
      perfusion at various stages in the development of OA in the Dunkin-Hartley guinea
      pig. DESIGN: Animals of four different ages (6, 9, 12 and 15 months),
      representing various stages in the development of OA, were studied. All animals
      underwent DCE MRI and perfusion data were analyzed based on the Brix two
      compartment pharmacokinetic model. Regions of interest were studied at the medial
      and lateral tibial plateaus and compared to histological-histochemical scores of
      articular cartilage and subchondral bone plate thickness. RESULTS: A decrease in
      perfusion as well as outflow obstruction was observed in animals between 6 and 9
      months of age, only in the medial tibial plateau subchondral bone. The eventual
      cartilage and bone lesions of OA occurred also in the medial tibia. Changes in
      perfusion occurred in the lateral tibia but not until OA lesions were
      established. Kinetic parameters of inflow were unchanged in both the medial and
      lateral plateaus. CONCLUSIONS: DCE MRI can be used to extract kinetic information
      on bone perfusion in an animal model of OA. The signal enhancement in subchondral
      bone temporally precedes and spatially localizes at the same site of the eventual
      bone and cartilage lesions. Time-intensity curves suggest outflow obstruction as
      an underlying mechanism.

PMID- 19409294
TI  - Fibronectin fragments mediate matrix metalloproteinase upregulation and cartilage
      damage through proline rich tyrosine kinase 2, c-src, NF-kappaB and protein
      kinase Cdelta.
AB  - OBJECTIVE: Since fibronectin fragments (Fn-fs) enhance cartilage damage through
      integrins, the objective was to investigate the role of integrin linked kinases,
      focal adhesion kinase (FAK) and a soluble form of FAK, proline rich tyrosine
      kinase 2 (Pyk2) and cellular src kinase (c-src) and the transcription factor,
      nuclear factor kappaB (NF-kappaB) in cartilage damage. METHODS: Bovine
      chondrocytes were cultured with various concentrations of three different Fn-fs,
      an amino-terminal 29 kDa, a gelatin binding 50 kDa and a central 140-kDa Fn-fs,
      each with progressively weaker cartilage damaging activity, or with native
      fibronectin (Fn), and lysates probed for activation of the selected kinases.
      Confocal microscopy was used to visualize intracellular location of activated
      kinases and NF-kappaB. Various kinase inhibitors were tested for their effects on
      Fn-f mediated upregulation of matrix metalloproteinase (MMP)-3 and -13 and
      cartilage proteoglycan (PG) depletion. RESULTS: The Fn-fs kinetically enhanced
      phosphorylation of FAK but did not show a clear dose-response effect. The 29-kDa
      and 50-kDa Fn-fs enhanced phosphorylation of Pyk2, c-src and NF-kappaB to a much
      greater extent than the 140-kDa Fn-f and native Fn and did so as a function of
      dose. The 29-kDa Fn-f enhanced the phosphorylation of nuclear Pyk2 as compared
      with no treatment or native Fn. Inhibitors of Pyk2, c-src, NF-kappaB and protein
      kinase Cdelta (PKCdelta) decreased MMP upregulation and decreased Fn-f mediated
      damage to cartilage. CONCLUSIONS: These studies enhance our knowledge of crucial
      factors in Fn-f mediated signaling in MMP upregulation and cartilage damage and
      because of the potential physiologic relevance of Fn-fs, provide a better
      knowledge of cartilage degeneration in general.

PMID- 19409296
TI  - [Cardiologists opinion on the situation of the secondary prevention of ischemic
      heart disease in Spain].

PMID- 19409295
TI  - Multimodal approach in the use of clinical scoring, morphological MRI and
      biochemical T2-mapping and diffusion-weighted imaging in their ability to assess
      differences between cartilage repair tissue after microfracture therapy and
      matrix-associated autologous chondrocyte transplantation: a pilot study.
AB  - OBJECTIVE: The aim of the present pilot study is to show initial results of a
      multimodal approach using clinical scoring, morphological magnetic resonance
      imaging (MRI) and biochemical T2-relaxation and diffusion-weighted imaging (DWI)
      in their ability to assess differences between cartilage repair tissue after
      microfracture therapy (MFX) and matrix-associated autologous chondrocyte
      transplantation (MACT). METHOD: Twenty patients were cross-sectionally evaluated
      at different post-operative intervals from 12 to 63 months after MFX and 12-59
      months after MACT. The two groups were matched by age (MFX: 36.0+/-10.4 years;
      MACT: 35.1+/-7.7 years) and post-operative interval (MFX: 32.6+/-16.7 months;
      MACT: 31.7+/-18.3 months). After clinical evaluation using the Lysholm score, 3T
      MRI was performed obtaining the MR observation of cartilage repair tissue
      (MOCART) score as well as T2-mapping and DWI for multi-parametric MRI.
      Quantitative T2-relaxation was achieved using a multi-echo spin-echo sequence;
      semi-quantitative diffusion-quotient (signal intensity without diffusion
      weighting divided by signal intensity with diffusion weighting) was prepared by a
      partially balanced, steady-state gradient-echo pulse sequence. RESULTS: No
      differences in Lysholm (P=0.420) or MOCART (P=0.209) score were observed between
      MFX and MACT. T2-mapping showed lower T2 values after MFX compared to MACT
      (P=0.039). DWI distinguished between healthy cartilage and cartilage repair
      tissue in both procedures (MFX: P=0.001; MACT: P=0.007). Correlations were found
      between the Lysholm and the MOCART score (Pearson: 0.484; P=0.031), between the
      Lysholm score and DWI (Pearson:-0.557; P=0.011) and a trend between the Lysholm
      score and T2 (Person: 0.304; P=0.193). CONCLUSION: Using T2-mapping and DWI,
      additional information could be gained compared to clinical scoring or
      morphological MRI. In combination clinical, MR-morphological and MR-biochemical
      parameters can be seen as a promising multimodal tool in the follow-up of
      cartilage repair.

PMID- 19409297
TI  - [Should routine screening for coeliac disease be considered in patients affected
      by chronic hepatitis C?].

PMID- 19409298
TI  - Targeted therapy for advanced non-small cell lung cancers: historical
      perspective, current practices, and future development. Foreword.

PMID- 19409299
TI  - Targeted therapy for advanced non-small cell lung cancers: historical
      perspective, current practices, and future development.

PMID- 19409300
TI  - The impact of compliant surfaces on in-hospital chest compressions: effects of
      common mattresses and a backboard.
AB  - PURPOSE: To evaluate, in a hospital setting, the influence of different, common
      mattresses, with and without a backboard, on chest movement during CPR. DESIGN
      AND SETTING: Sixty CPR sessions (140s each, 30:2, C:R ratio 1:1) were performed
      using a manikin on standard hospital mattresses, with or without a backboard in
      combination with variable weights. Sternum-to-spine compression distance was
      controlled (range 30-60mm) allowing evaluation of the underlying compliant
      surface on total hand travel. RESULTS: Movement of the caregiver's hands was
      significantly larger (up to 111mm at 50mm compression depth, p<0.0001) when
      sternum-to-spine compressions were performed without a backboard than with one.
      The extent of this variable extra travel effect depended on the type of mattress
      as well as the force of compression. Foam mattresses and air chamber systems act
      as springs and follow hand movement, while 'slow foam' mattresses incorporate
      time delays, making depth and force sensing harder. A backboard decreases the
      extra hand movement due to mattress effects by more than 50%, strongly reducing
      caregiver work. CONCLUSIONS: Total vertical hand movement is significantly, and
      clinically relevantly much, larger than sternum-to-spine compression depth when
      CPR is performed on a mattress. Additional movement depends on the type of
      mattress and can be strongly reduced, but not eliminated, when a backboard is
      applied. The additional motion and increased work load adds extra complexity to
      in-hospital CPR. We propose that this should be taken into account during
      training by in-hospital caregivers.

PMID- 19409301
TI  - Comparative effectiveness research: we must lead (so as not to be misled).

PMID- 19409302
TI  - Prediction of patient-reported outcome after single-bundle anterior cruciate
      ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to identify preoperative and
      intraoperative factors that predict patient-oriented outcome as measured by the
      International Knee Documentation Committee (IKDC) Subjective Knee Form after
      anterior cruciate ligament (ACL) reconstruction. METHODS: We identified 402
      subjects who had undergone primary single-bundle arthroscopic ACL reconstruction
      at a mean follow-up of 6.3 years (range, 2 to 15 years). The IKDC Subjective Knee
      Form was used to measure patient-reported outcome and was dichotomized as above
      or below the patient-specific age- and gender-matched population mean. Potential
      predictor variables included subject demographics, activity level before surgery,
      previous meniscectomy, and surgical variables. Multivariate logistic regression
      analysis was performed to identify the best subset of predictors for determining
      the likelihood that the IKDC score was better than the age- and gender-matched
      population mean. RESULTS: The dichotomized IKDC score was associated with body
      mass index (BMI), smoking status, education, previous medial meniscectomy, and
      medial chondrosis at the time of ACL reconstruction. The multivariate model
      containing only factors known before surgery included BMI and smoking status.
      Subjects with a BMI greater than 30 kg/m(2) had 0.35 times the odds of success as
      subjects with a normal BMI. Subjects who smoked had 0.36 times the odds of
      success as subjects who did not smoke. A model including medial chondrosis at the
      time of surgery had a slightly higher discriminatory power (area under the
      receiver operating characteristic curve, 0.65 v 0.61) and negative predictive
      value (71.4% v 60.0%) but similar positive predictive power (86.3% v 85.9%).
      CONCLUSIONS: Lower patient-reported outcome after ACL reconstruction was strongly
      associated with obesity, smoking, and severe chondrosis at the time of surgery.
      LEVEL OF EVIDENCE: Level III, prognostic case-control study.

PMID- 19409303
TI  - Equal kinematics between central anatomic single-bundle and double-bundle
      anterior cruciate ligament reconstructions.
AB  - PURPOSE: The purpose of this study was to compare the kinematics of a central
      anatomic single-bundle anterior cruciate ligament (ACL) reconstruction with a
      double-bundle ACL reconstruction by use of hamstring grafts and anatomic tunnel
      placement. METHODS: Anterior tibial translation and rotation were measured with a
      computer navigation system in 8 pairs of fresh-frozen cadaveric knees by use of a
      133-N anterior force, an internal and external torque of 10 Nm, and an anterior
      force (133 N) combined with an internal rotation torque (10 Nm). Tests were
      performed at 30 degrees and 60 degrees of flexion with the ACL intact, the ACL
      transected, and after reconstruction of one side of a pair with either a single
      or a double-bundle construct. RESULTS: At 30 degrees of flexion, cutting the ACL
      increased anterior translation under an anterior force (P < .0001), an internal
      rotation torque (P = .02), and a combined anterior force plus internal rotation
      torque (P = .01). At 60 degrees of flexion, transecting the ACL led to increased
      anterior translation only when an anterior force was used (P < .0001). Both
      single- and double-bundle reconstructions restored normal kinematics at 30
      degrees and 60 degrees of knee flexion. CONCLUSIONS: Central anatomic single
      bundle ACL reconstruction with tunnels centered within the tibial and femoral
      insertions and double-bundle ACL reconstruction can restore normal anterior
      translation to the knee under anterior and rotational loads applied at 30 degrees
      and 60 degrees of flexion. CLINICAL RELEVANCE: The primary kinematic effect of an
      ACL injury is an increase in anterior tibial translation, but there is no
      significant change in maximum internal or external rotation. Single- and double
      bundle ACL reconstructions are equally effective in restoring normal anterior
      translation to the knee under both anterior and rotational loads.

PMID- 19409304
TI  - The accuracy of magnetic resonance imaging scanning and its influence on
      management decisions in knee surgery.
AB  - PURPOSE: The purpose of our study was to evaluate the impact of preoperative
      magnetic resonance imaging (MRI) assessment of articular knee pathology on the
      clinical management of patients presenting with joint line pain. METHODS: A
      preliminary study on 100 patients was performed to assess the accuracy of
      specific MRI sequences, using arthroscopy as a gold standard. Six hundred and
      eighteen consecutive patients with knee symptoms presenting to 2 specialist knee
      surgeons were then recruited. A clinical diagnosis of an arthroscopically
      treatable lesion was made in all cases. Clinical assessment data were correlated
      to subsequent MRI findings, recording any discrepancy and in particular whether
      or not MRI findings influenced management decisions. RESULTS: In the preliminary
      study, MRI sequences had an overall sensitivity of 83.2% and a specificity of
      94.3% for the detection of chondral lesions. However, when considering
      arthroscopic grade III and IV lesions, MRI sensitivity and specificity were
      improved to 84.5% and 97.1%. In the second phase of the study, 141 (22.8%) of the
      618 patients presenting with knee symptoms had an altered clinical management
      subsequent to MRI. The presence of unexpected chondral lesions was found in 77 of
      these patients. Conversely, 22 patients with clinical symptoms suspicious for
      simple chondral degeneration had unstable meniscal tears. CONCLUSIONS: We suggest
      that preoperative MRI scanning identifies a group of patients who have more
      advanced degenerative joint disease than the clinical assessment and the plain
      radiographs suggest. This would expedite definitive surgery in patients with
      advanced osteoarthritis on MRI scans. LEVEL OF EVIDENCE: Level II, development of
      diagnostic criteria on basis of consecutive patients with universally applied
      gold standard.

PMID- 19409305
TI  - Potential risks of femoral tunnel drilling through the far anteromedial portal: a
      cadaveric study.
AB  - PURPOSE: The purpose of this study was to estimate the potential risks when
      drilling femoral tunnels through the far anteromedial portal in double-bundle
      anterior cruciate ligament reconstruction in cadaveric knees. METHODS: Ten
      cadaveric knees were used. We drilled the anteromedial bundle (AMB) and
      posterolateral bundle (PLB) through the far anteromedial portal at 3 different
      knee flexion angles: 70 degrees, 90 degrees, and 110 degrees. We measured the
      shortest distance to the common peroneal nerve and the posterior articular
      cartilage of the lateral femoral condyle and the femoral tunnel length. RESULTS:
      At 70 degrees, the distance to the nerve was less than 10 mm in 7 AMB cases and
      in 9 PLB cases, and the distance to the cartilage was less than 10 mm in all the
      AMB and PLB cases. At 90 degrees, the distance to the nerve was less than 10 mm
      in 1 AMB and 5 PLBs, and the distance to the cartilage was less than 10 mm in 2
      AMBs and all the PLBs. On the other hand, at 110 degrees , the distance to the
      nerve was greater than 10 mm in all the AMBs and PLBs, and the distance to the
      cartilage did not exceed 10 mm in just 2 of the PLBs. CONCLUSIONS: In our
      cadaveric study we found that the low knee flexion angles when drilling femoral
      tunnels through the far anteromedial portal might have the potential risks of
      damage to the common peroneal nerve and the posterior articular cartilage, and
      the risks would be decreased at higher degrees of knee flexion. However, we found
      there was a 20% risk of damage to the cartilage while drilling the PLB at 110
      degrees. CLINICAL RELEVANCE: High knee flexion angles are recommended to avoid
      damage to the nerve and the cartilage when drilling femoral tunnels through the
      far anteromedial portal in double-bundle anterior cruciate ligament
      reconstruction.

PMID- 19409306
TI  - Navigation evaluation of the pivot-shift phenomenon during double-bundle anterior
      cruciate ligament reconstruction: is the posterolateral bundle more important?
AB  - PURPOSE: The purpose of this study was to assess the pivot-shift phenomenon
      during double-bundle anterior cruciate ligament (ACL) reconstruction using a
      navigation system. METHODS: Ninety patients who received navigated double-bundle
      ACL reconstruction were included in this study. The mean age of the patients was
      21.9 years. During reconstruction, pivot-shift tests were performed 4 times:
      before reconstruction, after the posterolateral bundle fixation, after the
      anteromedial bundle fixation, and after the double-bundle reconstruction. Both
      tibial internal rotation and anterior translation under the pivot-shift test were
      measured at each phase by the additional functions of the navigation. The
      navigation system used in this study was the image-free, which does not require
      preoperative or intraoperative images, OrthoPilot ACL (version 2.0; B. Braun
      Aesculap, Tuttlingen, Germany). RESULTS: Before ACL reconstruction, average (+/-
      standard deviation) tibial internal rotation and anterior translation under the
      pivot-shift test were 23.7 degrees +/- 6.1 degrees and 5.2 +/- 2.4 mm. They were
      significantly decreased to 20.9 degrees +/- 6.4 degrees and 2.3 +/- 1.1 mm after
      the posterolateral bundle fixation, and also decreased to 22.2 degrees +/- 5.7
      degrees and 2.4 +/- 1.1 mm after the anteromedial bundle fixation. There was no
      significant difference between the groups. After double-bundle reconstruction,
      they improved to 20.3 degrees +/- 6.3 degrees and 2.0 +/- 1.0 mm. CONCLUSIONS:
      Our results indicate that both the posterolateral and the anteromedial bundle
      similarly control both anterior translation and internal rotation during pivot
      shift testing. Double-bundle reconstruction may further improve knee stability.
      LEVEL OF EVIDENCE: Level II, development of diagnostic criteria on basis of
      consecutive patients with universally applied reference gold standard.

PMID- 19409307
TI  - Results of subtotal/total or partial meniscectomy for discoid lateral meniscus in
      children.
AB  - PURPOSE: The purpose of this study was to compare the midterm outcomes of
      subtotal/total meniscectomy with those of partial meniscectomy for symptomatic
      torn discoid lateral meniscus (DLM) in children and evaluate the correlation of
      chondral wear in the lateral compartment at index surgery with arthritic changes
      at final follow-up. METHODS: We reviewed 43 knees in 36 patients aged less than
      15 years who underwent arthroscopic procedures for torn DLMs between 1999 and
      2004. The mean patient age at the time of surgery was 9.5 years (range, 5 to 14
      years), and the mean follow-up period was 4.3 years (range, 2.1 to 9.4 years). Of
      the 43 knees, 23 underwent partial meniscectomy and 20 underwent subtotal/total
      meniscectomy. The status of the articular cartilage at the time of surgery was
      analyzed with the Outerbridge grading system, and radiologic arthritic changes of
      the lateral compartment at final follow-up were evaluated by use of the
      classification of Tapper and Hoover. RESULTS: Clinically excellent or good
      results at final follow-up were observed in 36 of 43 knees (83.7%). There was no
      difference between the partial and subtotal/total meniscectomy groups in terms of
      the presence of chondromalacia of the lateral compartment at the time of surgery.
      Radiologic arthritic changes at final follow-up were significantly more severe in
      the subtotal/total meniscectomy group than in the partial meniscectomy group (P <
      .001). We observed a positive linear association between the degree of chondral
      wear of the lateral tibial plateau at the time of surgery and subsequent
      development of radiologic signs of arthritic change at last follow-up (rho =
      .628, P = .027). We also found a correlation between symptom duration and
      chondromalacia of the lateral tibial plateau (rho = .684, P = .021). CONCLUSIONS:
      Although there were no differences in clinical results between the partial and
      subtotal/total meniscectomy groups, partial meniscectomy yielded better
      radiologic results than subtotal/total meniscectomy for torn DLMs in children.
      Our findings suggest the need for early diagnosis and greater caution in the
      treatment of torn DLMs in children. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 19409308
TI  - The compressive behavior of the human glenoid labrum may explain the common
      patterns of SLAP lesions.
AB  - PURPOSE: The aim of the study was to define the normalized compressive stiffness
      (modulus) of the glenoid labrum around its circumference and to characterize the
      difference in modulus between different areas. METHODS: Sixteen fresh-frozen
      cadaveric shoulders were harvested and dissected down to the glenoid labrum. Any
      specimens with significant degenerative changes were discarded, leaving 8 labra
      for testing. The labrum was divided into 8 segments, to allow comparison around
      its circumference. A uniform testing specimen was produced from each area by use
      of a microtome. Each specimen measured 3 x 1 mm in cross section and was 6 mm in
      length. Indentation testing was conducted in a controlled environment of 100%
      humidity at 37 degrees C +/- 1 degrees C. RESULTS: We obtained 52 test samples
      from 8 labra. The mean modulus of the glenoid labrum was 69.7 megapascal
      (standard deviation, 36.2 megapascal). The anterosuperior portion of the labrum
      had a higher modulus than the posteroinferior portion (P = .0075). CONCLUSIONS:
      This study has shown that the human glenoid labrum's compressive behavior varies
      around its circumference. The greater modulus of the anterosuperior portion of
      the labrum supports the theory that this area is anatomically different from the
      rest of the labrum and resists compressive loads. CLINICAL RELEVANCE: These
      results may explain why the common type of SLAP lesions seen show failure at the
      interface between the labrum and the glenoid rather than within the substance of
      the labrum itself.

PMID- 19409309
TI  - The effect of forced-air warming during arthroscopic shoulder surgery with
      general anesthesia.
AB  - PURPOSE: The aim of this study was to compare the change in body temperature
      between the cotton blanket group and forced-air warming blanket group during
      arthroscopic shoulder surgery. In both groups irrigation fluid at room
      temperature (22 degrees C) was used. METHODS: We randomly assigned 44 American
      Society of Anesthesiologists physical status I and II patients scheduled for
      elective shoulder arthroscopic surgery to receive 1 cotton blanket (group I, n =
      22) or a forced-air warming blanket (group II, n = 22). Body temperatures were
      measured with an esophageal stethoscope, which was inserted immediately after
      intubation. RESULTS: A significant difference in body temperatures was observed
      at 60 minutes after induction (P = .0192), 90 minutes after induction (P =
      .0004), 120 minutes after induction (P = .0003), and 150 minutes after induction
      (P = .0228). Shivering on arrival in the postanesthesia care unit was found in 15
      patients in group I (68.1%) and only 1 patient in group II (4.5%). CONCLUSIONS:
      We conclude that forced-air warming is significantly more efficient than a cotton
      blanket alone at maintaining perioperative normothermia during arthroscopic
      shoulder surgery. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

PMID- 19409310
TI  - Anatomic and biomechanical study of the biceps vinculum, a structure within the
      biceps sheath.
AB  - PURPOSE: To evaluate the anatomic, biomechanical, and histologic properties of
      the biceps vinculum and its potential role as a restraint to distal migration of
      the biceps after tenotomy. METHODS: Eight human shoulders were dissected to
      define the anatomic parameters of the biceps vinculum. Histologic studies were
      performed by sectioning through the vinculum-tendon attachment and performing H&E
      staining. The strength of the vinculum was tested biomechanically after
      sectioning the biceps origin and applying a uniaxial tension at a rate of 1 mm/s
      until failure. RESULTS: With regard to anatomy, the vinculum was present in all
      specimens, attached to the biceps tendon and proximal humerus. Excursion testing
      showed that the vinculum prevented the biceps origin from migrating distal to the
      groove entrance. The mean dimensions of the structures and excursion were as
      follows: biceps origin to vinculum, 43.4 mm; vinculum width on biceps side, 46.2
      mm; vinculum width on bone side, 69.3 mm; length of tendon with proximal pull,
      42.6 mm; and length of tendon with distal pull, 2.25 mm. With regard to
      histology, the membranous tissue of the biceps vinculum consisted of loose soft
      tissue with fat, arteries, and veins. The vinculum was seen to loosely attach to
      the biceps tendon and more intimately attach to the periosteal/bone side. With
      regard to biomechanical testing, the maximum force to failure of the vinculum was
      variable, ranging from 17.4 N to 227.6 N, with a mean value of 102.7 +/- 76 N.
      CONCLUSIONS: The biceps vinculum was a consistent membranous structure intimately
      associated with the biceps tendon and attached to the proximal humerus. After
      tenotomy at the biceps origin, the vinculum prevented distal migration of the
      proximal biceps tendon past the groove entrance in all specimens. Biomechanical
      testing showed that the vinculum provided variable resistance to distal pull.
      CLINICAL RELEVANCE: The properties described may help to explain why biceps
      tenotomy does not routinely result in a Popeye biceps deformity.

PMID- 19409311
TI  - Magnetic resonance imaging of the postoperative meniscus.
AB  - Imaging of the postoperative meniscus is a challenge. Nevertheless, magnetic
      resonance imaging (MRI) of the symptomatic knee after meniscal surgery is a
      valuable diagnostic study of both the menisci and the entire joint. At present,
      symptomatic patients who have had partial meniscectomy of less than 25% may be
      evaluated by MRI. For those with partial meniscectomy of greater than 25% or
      after meniscal repair, direct or indirect magnetic resonance arthrography (MRA)
      should be considered. Currently, the decision of whether to perform direct (intra
      articular) versus indirect (intravenous) MRA must be reviewed on a case-by-case
      basis considering both the patient's ability to tolerate intra-articular
      injection and whether a significant effusion already exists, which will imbue the
      tear with synovial fluid (making intra-articular injection of less importance).
      In such cases of significant effusion, indirect MRA would be preferred. If MRI or
      MRA is contraindicated, computed tomography arthrography seems a promising
      alternative. For a patient who has undergone meniscal allograft transplantation,
      MRI seems adequate for detecting meniscocapsular healing, allograft extrusion,
      and allograft tear. Future improvements in MRI sequencing may obviate the need
      for invasive modalities.

PMID- 19409312
TI  - Cell-based therapy in articular cartilage lesions of the knee.
AB  - PURPOSE: The purpose of this systematic review was to determine the effectiveness
      of cell-based therapy for articular cartilage defects of the knee. METHODS: We
      performed a literature search in Medline (1994 to 2009) regarding cell-based
      therapies for chondral lesions. RESULTS: We identified 10 Level I or II
      randomized controlled trials and 3 Level II prospective comparative studies.
      Although many of these studies had substantial flaws, which could introduce bias,
      we overall found no difference between the cell-based studies and other
      interventions. In addition, we identified 26 Level III and IV studies of cell
      based therapy. CONCLUSIONS: There is insufficient evidence from the studies
      included in this review to say whether cell-based therapy is superior to other
      treatment strategies in articular cartilage lesions of the knee.

PMID- 19409313
TI  - Anatomic reduction and next-generation fixation constructs for arthroscopic
      repair of crescent, L-shaped, and U-shaped rotator cuff tears.
AB  - Emerging techniques and instrumentation have allowed orthopaedic surgeons to
      achieve rotator cuff repair through an all-arthroscopic technique. The most
      critical steps in rotator cuff repair consist of proper identification of the
      cuff tear pattern and anatomic restoration of the torn tendon footprint. With
      anatomic reduction of the rotator cuff tendons, a sound fixation construct can
      help restore rotator cuff contact pressure and kinematics, allowing for decreased
      repair tension and optimal healing potential. We provide surgical methods to
      recognize tear patterns and present a repair construct that will restore the
      anatomic footprint of the torn rotator cuff tendon. The key, initial maneuver to
      restore the anatomic footprint of the cuff includes placement of a suture anchor
      at the anterolateral corner for L-shaped tears and at the posterolateral corner
      for reverse L-shaped and U-shaped tears. After insertion of the medial-row
      anchors, the tendon stitches should be planned by use of a grasper to hold the
      tendon in a reduced position and guide location of the stitch. The lateral row
      with suture bridge can be visualized, and the final repair construct should
      produce an anatomic restoration of the rotator cuff footprint.

PMID- 19409314
TI  - Glenoid rim fracture in contact athletes with absorbable suture anchor
      reconstruction.
AB  - Absorbable suture anchors are widely used in arthroscopic shoulder reconstruction
      procedures and provide a good solution for stabilization in athletes. In our
      practice we identified a group of 3 patients who had participated in contact
      sports and in whom traumatic instability developed. Subluxation of the shoulder
      followed repair by use of absorbable suture anchors. Each patient had a new
      injury characterized by a glenoid rim fracture that was not amenable to further
      arthroscopic reconstruction and was revised by use of a modified Latarjet
      procedure. All patients successfully returned to contact sports. We conclude that
      resorption defects resulting from the use of absorbable anchors contribute to an
      increased risk of rim fracture.

PMID- 19409315
TI  - The anterior medial portal.

PMID- 19409317
TI  - Challenges and risks of the anteromedial portal.

PMID- 19409320
TI  - Anatomic femoral plug placement of BPTB to mimic natural fiber arrangement is not
      new.

PMID- 19409323
TI  - Topical anesthetics demand respect.

PMID- 19409324
TI  - Compound topical anesthetics in orthodontics: putting the facts into perspective.

PMID- 19409326
TI  - Decalcification and tooth clustering.

PMID- 19409327
TI  - Developing our role as "clinical biologists".

PMID- 19409328
TI  - Methodology for orthodontic anchorage study questioned.

PMID- 19409333
TI  - Dental and skeletal changes associated with Class II surgical-orthodontic
      treatment.
AB  - INTRODUCTION: Few published reports detail the dental changes produced by
      orthodontic treatment in conjunction with orthognathic surgery. METHODS: Thirty
      four Class II subjects who underwent surgical-orthodontic treatment with
      mandibular advancement and rigid fixation were selected, and their lateral
      cephalograms were digitized. Mean skeletal and dental values were calculated for
      pretreatment, presurgical, and final treatment times. Treatment efficacy as a
      percentage of an ideal goal achieved also was calculated. RESULTS: All data
      showed significant positive changes in the position of the mandible. The mean
      changes showed that the maxillary incisors were overretracted presurgically and
      then returned to a normal position postsurgically, whereas the mandibular
      incisors were proclined and protruded presurgically and remained so at
      posttreatment. The efficacy data showed that the incisors were not ideally
      decompensated in many patients. CONCLUSIONS: The efficacy data show that
      presurgical orthodontic treatment often does not fully decompensate the incisors;
      this then limits the surgical outcome.

PMID- 19409331
TI  - Mini-implants in orthodontics: a systematic review of the literature.
AB  - INTRODUCTION: In this article, we systematically reviewed the literature to
      quantify success and complications encountered with the use of mini-implants for
      orthodontic anchorage, and to analyze factors associated with success or failure.
      METHODS: Computerized and manual searches were conducted up to March 31, 2008,
      for clinical studies that addressed these objectives. The selection criteria
      required that these studies (1) reported the success rates of mini-implants on
      samples sizes of 10 implants or more, (2) gave a definition of success, (3) used
      implants with a diameter smaller than 2.5 mm, and (4) applied forces for a
      minimum duration of 3 months. Factors associated with implant success were
      accepted only if potentially influencing variables were controlled. The Cochrane
      Handbook for Systematic Reviews of Interventions was used as the guideline for
      this article. RESULTS: Nineteen reports met the inclusion criteria, but
      definitions of success, duration of force application, and quality of the
      methodology of these studies varied widely. Rates of primary outcomes ranged from
      0% to 100%, but most articles reported success rates greater than 80% if mobile
      and displaced implants were included as successful. Adverse effects of miniscrews
      included biologic damage, inflammation, and pain and discomfort. Only a few
      articles reported negative outcomes. All proposed correlations between clinical
      success and specific variables such as implant, patient, location, surgery,
      orthodontic, and implant-maintenance factors were rejected because they did not
      meet the selection criteria for controlling those variables. CONCLUSIONS: Mini
      implants can be used as temporary anchorage devices, but research in this field
      is still in its infancy. Interpretation of findings was conditioned by lack of
      clarity and poor methodology of most studies. Questions concerning patient
      acceptability, rate and severity of adverse effects of miniscrews, and variables
      that influenced success remain unanswered. This article includes a guideline for
      future studies of these issues, based on specific definitions of primary and
      secondary outcomes correlated with specific operational variables.

PMID- 19409335
TI  - Dentofacial features of Class II malocclusion associated with maxillary skeletal
      protrusion: a longitudinal study at the circumpubertal growth period.
AB  - INTRODUCTION: The purpose of this study was to describe the craniofacial growth
      changes of subjects with Class II malocclusion associated with maxillary skeletal
      protrusion at the circumpubertal growth period. METHODS: The records of 25
      untreated subjects with normal Class I occlusion and 25 untreated Class II
      subjects (14 boys and 11 girls in each group) were selected from the longitudinal
      records of the University of Michigan Growth Study. All Class II subjects had
      maxillary protrusion. Measurements were made on lateral and posteroanterior
      cephalograms and on dental casts at 2 times. The first observation (T1) was
      during the prepubertal growth phase (vertebral stages CS1 to CS3). The second
      observation (T2) was during the postpubertal phase of growth (vertebral stages
      CS4 to CS6). The following comparisons were made: Class I vs Class II at T1,
      Class I vs Class II at T2, and growth changes in Class I vs Class II. RESULTS: No
      dentofacial feature studied showed any statistically significant difference when
      comparing the growth changes between the Class II and the Class I groups.
      CONCLUSIONS: These results suggest that dentofacial features of Class II
      malocclusion associated with maxillary skeletal protrusion are maintained during
      the circumpubertal period, and that growth changes in this type of Class II
      disharmony are similar to those in subjects with normal occlusion.

PMID- 19409338
TI  - Orthodontic examiners seek synchronization.

PMID- 19409337
TI  - Long-term treatment effects of the FR-2 appliance of Frankel.
AB  - INTRODUCTION: The objective of this study was to evaluate the long-term
      effectiveness in a group treated with the FR-2 appliance of Frankel compared with
      an untreated Class II control group. METHODS: The sample consisted of 30 patients
      (17 boys, 13 girls) treated exclusively with the FR-2 by Rolf Frankel. The mean
      age at the start of treatment was 8 years (T1), with a posttreatment cephalogram
      (T2) taken 10 years later. The control group included 20 subjects (11 boys, 9
      girls) with untreated Class II malocclusion. Their mean ages at T1 and T2, and
      the mean times of observation, matched the treatment group closely. Lateral
      cephalograms were analyzed with a specific tracing regimen at both T1 and T2 in
      both groups. The Student t test was used to compare changes between the groups
      RESULTS: The FR-2 group maintained stable correction of the initial Class II
      malocclusion over the evaluation period. Significant mandibular and
      intermaxillary changes and dentoalveolar changes were noted in the treated group,
      with a 3-mm long-term increase in mandibular length compared with the untreated
      Class II controls. CONCLUSIONS: This study suggests that correction of a Class II
      malocclusion with the FR-2 appliance maintains favorable results over the long
      term with both skeletal and dentoalveolar changes.

PMID- 19409340
TI  - Early treatment for Class II malocclusion and perceived improvements in facial
      profile.
AB  - INTRODUCTION: The aims of this study were to assess whether early Twin-block
      appliance treatment improves the attractiveness of Class II profiles and to
      determine the orofacial features of a profile that most influence the perception
      of attractiveness. METHODS: Silhouetted profiles of 20 treated patients and 20
      untreated controls randomly selected from 174 subjects (ages, 8-10 years) of a
      randomized, controlled trial into the effectiveness of early Class II treatment
      were assessed by 30 children (ages, 10-11 years) and 24 teaching staff using a 5
      point Likert scale. Independent samples t tests were used to compare
      attractiveness ratings between the treated and untreated groups. Linear
      regression was used to determine the features defining attractiveness. RESULTS:
      Early orthodontic treatment resulted in improved perceptions of facial profile
      attractiveness. Profiles were likely to be rated as attractive if the overjet was
      smaller (P = 0.001) and no teeth showed (P <0.05). CONCLUSIONS: Profile
      silhouettes of children who had received early orthodontic treatment for Class II
      malocclusion were perceived to be more attractive by peers than those of children
      who did not receive treatment.

PMID- 19409339
TI  - Early treatment for Class II Division 1 malocclusion with the Twin-block
      appliance: a multi-center, randomized, controlled trial.
AB  - INTRODUCTION: The aim of this study was to evaluate the effectiveness of early
      orthodontic treatment with the Twin-block appliance for the treatment of Class II
      Division 1 malocclusion. This was a multi-center, randomized, controlled trial
      with subjects from 14 orthodontic clinics in the United Kingdom. METHODS: The
      study included 174 children aged 8 to 10 years with Class II Division 1
      malocclusion; they were randomly allocated to receive treatment with a Twin-block
      appliance or to an initially untreated control group. The subjects were then
      followed until all orthodontic treatment was completed. Final skeletal pattern,
      number of attendances, duration of orthodontic treatment, extraction rate, cost
      of treatment, and the child's self-concept were considered. RESULTS: At the end
      of the 10-year study, 141 patients either completed treatment or accepted their
      occlusion. Data analysis showed that there was no differences between those who
      received early Twin-block treatment and those who had 1 course of treatment in
      adolescence with respect to skeletal pattern, extraction rate, and self-esteem.
      Those who had early treatment had more attendances, received treatment for longer
      times, and incurred more costs than the adolescent treatment group. They also had
      significantly poorer final dental occlusion. CONCLUSIONS: Twin-block treatment
      when a child is 8 to 9 years old has no advantages over treatment started at an
      average age of 12.4 years. However, the cost of early treatment to the patient in
      terms of attendances and length of appliance wear is increased.

PMID- 19409341
TI  - Long-term soft-tissue response to orthodontic treatment with early cervical
      headgear--a randomized study.
AB  - INTRODUCTION: The purpose of this longitudinal randomized investigation was to
      determine the long-term changes in the soft-tissue profile during orthodontic
      treatment when treatment is started with headgear (HG) in the early mixed
      dentition. METHODS: The subjects were 68 children (28 girls, 40 boys; mean age,
      7.6 years; SD, 0.3 years) with a Class II tendency in occlusion and moderate
      crowding. They were randomly divided into 2 groups. In the HG group, treatment
      began immediately. No other appliances were used during the first 2 years. In the
      control group, only minor interceptive procedures were performed during the first
      follow-up period of 2 years. During the 8-year follow-up, orthodontic treatment,
      if needed, comprised fixed appliances and possible extractions in both groups.
      Twenty linear and 5 angular soft-tissue measurements were registered from lateral
      cephalograms taken before treatment and after follow-up-periods of 2, 4, and 8
      years. RESULTS: The major findings were that, at the 8-year follow-up, the soft
      tissue chin and the lower lip were significantly thicker, and the mentolabial
      sulcus was significantly deeper in the HG group than in the control group. In the
      control group, a larger variation in the upper lip position was found because of
      more extractions in this group. CONCLUSIONS: Early HG treatment has only a minor
      effect on the soft-tissue profile. The main effects are on the thickness of the
      soft-tissue chin and the contour of the lower lip. The differences were not
      otherwise significant during the long-term follow-up.

PMID- 19409342
TI  - Efficiency of mandibular arch alignment with 2 preadjusted edgewise appliances.
AB  - INTRODUCTION: The aim of this study was to compare the efficiency of mandibular
      arch alignment in 3 dimensions with a self-ligating bracket system (SmartClip, 3M
      Unitek, Monrovia, Calif) and a conventional preadjusted edgewise twin bracket
      (Victory, 3M Unitek) in nonextraction patients. This was a prospective,
      randomized, controlled clinical trial at the Royal London Hospital, School of
      Dentistry, and Kent and Canterbury Hospital, United Kingdom. Sixty-six
      consecutive patients satisfying the inclusion criteria were enrolled in the
      study. They were randomly allocated with a computer-generated system to 1 of the
      2 bracket systems. METHODS: Pretreatment mandibular arch irregularity was
      measured by using a coordinate measuring machine (Merlin II, International
      Metrology Systems, Gloucester, United Kingdom). A 0.016-in round martensitic
      active nickel-titanium aligning archwire (3M Unitek) was placed in all subjects.
      Mandibular arch irregularity was remeasured 8 weeks later. RESULTS: Sixty-five
      subjects completed the study. Bracket type had little influence on alignment
      efficiency overall (P = 0.08), or in the buccal (P = 0.173) or labial segments (P
      = 0.528) after adjustment for pretreatment differences by analysis of covariance
      (ANCOVA). Alignment efficiency was highly correlated to pretreatment irregularity
      overall (P <0.001), both in the buccal (P = 0.001) and labial (P <0.001)
      segments. Increasing age appeared to have a negative effect on alleviation of
      irregularity, although this effect did not reach statistical significance (P =
      0.053). CONCLUSIONS: The null hypothesis that efficiency of alignment in the
      mandibular arch in nonextraction patients is independent of bracket type was
      accepted. Alignment efficiency is largely influenced by initial irregularity.

PMID- 19409343
TI  - Effect of different bonding agents on prevention of enamel demineralization
      around orthodontic brackets.
AB  - INTRODUCTION: Demineralization around the bracket is an undesired side effect of
      orthodontic treatment. The aim of this in-vitro study was to evaluate the
      efficacy of 5 bonding agents to prevent enamel demineralization. Two
      quantification methods were used. METHODS: Eighty-five extracted teeth were
      randomly allocated to 5 groups: (1) Transbond Plus SEP and Transbond XT (both, 3M
      Unitek, Seefeld, Germany), (2) 37% phosphoric acid, Pro Seal (Reliance
      Orthodontic Products, Itasca, Ill) and Transbond XT, (3) Clearfil Protect Bond
      (Kuraray Medical, Okayama, Japan) and Transbond XT, (4) 37% phosphoric acid and
      Light Bond (Reliance Orthodontic Products), and (5) Ortho Conditioner and Fuji
      Ortho LC (both, GC, Tokyo, Japan). In-vitro caries was created by pH cycling for
      30 days. After demineralization, the teeth were scanned with a commercial cone
      beam microtomographic system. Then the teeth were examined by polarized light
      microscopy. RESULTS: The 2 methods of examination showed significant differences
      among the 5 groups according to lesion depth and mineral loss (P < 0.01). The
      resin-modified glass ionomer cement (group 5) had the lowest values for lesion
      depth and mineral loss. CONCLUSIONS: Fuji Ortho LC showed a significantly smaller
      lesion depth and less mineral loss compared with the other materials. The cone
      beam microtomographic system is suitable for evaluation of subsurface lesions and
      has considerable advantages.

PMID- 19409344
TI  - Failure rate of brackets bonded with antimicrobial and fluoride-releasing, self
      etching primer and the effect on prevention of enamel demineralization.
AB  - INTRODUCTION: Our aim in this randomized clinical trial was to compare the
      failure rates of orthodontic brackets by using 2 self-etching primers (SEPs)
      (Transbond Plus [3M Unitek, Seefeld, Germany] and Clearfil Protect Bond [Kuraray
      Medical, Okayama, Japan]) with a split-mouth design. Additionally, the effect of
      Clearfil Protect Bond was investigated regarding inhibition of plaque
      accumulation and demineralization. METHODS: A total of 480 brackets were bonded
      in 24 patients with the SEPs. The observation period was 12 months. One week
      after bonding and at every third recall, the plaque index and a visual rating of
      the enamel adjacent to the bracket were assessed at the lateral incisors and the
      first premolars. Additionally, DIAGNOdent (KaVo, Biberach, Germany) values were
      measured. RESULTS: Over the investigation time, 26 failures were recorded. Five
      occurred with the brackets bonded with Transbond Plus, and the rest with Clearfil
      Protect Bond (P = 0.002). The additionally observed parameters had no significant
      differences. CONCLUSIONS: The failure rate with Clearfil Protect Bond was
      significantly higher. For our patients, who had adequate oral hygiene, there was
      no benefit with regard to plaque accumulation and prevention of demineralization
      with Clearfil Protect Bond.

PMID- 19409345
TI  - Comparison of Chinese and US orthodontists' averaged evaluations of "facial
      attractiveness" from end-of-treatment facial photographs.
AB  - INTRODUCTION: This study continues our assessment of agreement and disagreement
      among 25 Chinese and 20 US orthodontists in the ranking for facial attractiveness
      of end-of-treatment photographs of randomly sampled growing Chinese and white
      orthodontic patients. The main aims of this article were to (1) measure the
      overall pattern of agreement between the mean rankings of US and Chinese
      orthodontists, and (2) measure the strength of agreement between the rankings of
      the US and Chinese orthodontists for each patient. METHODS: Each judge
      independently ranked standard clinical sets of profile, frontal, and frontal
      smiling photographs of 43 US patients and 48 Chinese patients. For each patient,
      a separate mean rank was computed from the responses of each group of judges.
      Pearson correlations between the mean ranks of the 2 groups of judges were used
      to measure their overall agreement. Paired and unpaired t tests were used to
      measure the agreement between the judges of the 2 groups for each patient.
      RESULTS: The overall agreement between the mean rankings of the US and Chinese
      judges was very high. For the US patients, the correlation between the Chinese
      and US judges means was r = 0.92, P <0.0001. For the Chinese patients, the
      analogous value was r = 0.86, P <0.0001. Agreement between the 2 groups of judges
      concerning each patient was also generally strong. For two thirds of the
      patients, the mean ranks of the US and Chinese judges differed by less than 1
      unit in a scale of 12. However, for 6 patients considered individually (5 Chinese
      and 1 US), the assessment of the 2 groups of judges was statistically
      significantly different at P values ranging from 0.02 to less than 0.0001, even
      after the Bonferroni correction. CONCLUSIONS: These findings demonstrate that
      orthodontic clinicians can reliably identify and rank subtle differences between
      patients, and that differences between judges and between patients can be
      distinguished at a high level of statistical significance, given appropriate
      study designs. However, the reasons clinicians give for the differences in their
      judgments are more difficult to investigate and will require further study.

PMID- 19409346
TI  - Evaluation of interdental space of the maxillary posterior area for orthodontic
      mini-implants with cone-beam computed tomography.
AB  - INTRODUCTION: Our objectives in this study were to measure in a group of patients
      the interradicular spaces between the maxillary second premolar and first molar,
      which is often used as placement sites for mini-implants, and to suggest simple
      guidelines for safe placement. METHODS: Cone-beam computed tomography was used in
      35 patients to measure interdental spaces and distances between the surface of
      the cortical bone and the closest interradicular area apically in 1-mm intervals
      in 9 axial images from the cementoenamel junction (CEJ). The cone-beam computed
      tomography data were analyzed by using anlaysis of variance (ANOVA) to evaluate
      the differences in interradicular distances, cortical bone surfaces, and
      narrowest interradicular spaces. A t test was also performed to evaluate sex and
      placement side differences. RESULTS: Interradicular space became wider toward the
      apical area; several axial planes showed statistically nonsignificant differences
      from the CEJ to the root, and the average distance from the surface of the
      cortical bone to the area of the closest interradicular space was over 5 mm in
      the most sections. CONCLUSIONS: Guidelines for safe placement are as follows: the
      initial point for mini-implant placement is near the mucogingival line (2-4 mm
      from the CEJ) and less than a 45 degrees apical angulation to the long axis of
      tooth, with a mini-implant diameter of 1.4 to 1.8 mm and length of about 6 mm
      (bone contact). A larger placement angle would increase the cortical bone
      contact; however, it is difficult to apply various traction materials and might
      increase the danger of maxillary sinus perforation.

PMID- 19409347
TI  - Soft bone primary stability of 3 different miniscrews for orthodontic anchorage:
      a resonance frequency investigation.
AB  - INTRODUCTION: Several miniscrews are available for skeletal anchorage. They have
      different geometries with self-drilling or self-tapping features. The aim of this
      study was to evaluate the soft bone primary stability of 3 different orthodontic
      screws by using the resonance frequency analysis. METHODS: Aarhus mini-implant
      (Aarhus Mini-implant, Charlottenlund, Denmark) (A), Mini Spider Screws (HDC,
      Sarcedo, Italy) (S), and Micerium Anchorage System (Micerium, Avegno, Italy)
      (MAS) were investigated. To be compatible with the device used for resonance
      frequency analysis, the screws were modified (an abutment [Astra Tech, Molndal,
      Sweden] was soldered on top). Four screws per system were tested. Each screw was
      placed in 5 excised rabbit femoral condyles, providing experimental models of
      soft bone. Placement was drill-free for the A screw, whereas the MAS and S screws
      required a pilot hole through the cortical layer. After each placement procedure,
      resonance frequency was assessed as a parameter of primary stability. Differences
      among the systems were analyzed by using analysis of variance for repeated
      measures, with the level of significance at P < 0.05. RESULTS: The recorded
      resonance frequencies (in Hz) were (mean +/- SD): MAS, 6236.1 +/- 192.1; S,
      6270.1 +/- 99.7; and A, 6193.1 +/- 142.4. Differences among the groups were not
      statistically significant (P > 0.05). CONCLUSIONS: The resonance frequency
      analysis is applicable to comparatively assess the primary stability of
      orthodontic miniscrews. The 3 systems had similar outcomes in an experimental
      model of soft bone.

PMID- 19409348
TI  - Maxillary and mandibular arch widths of Colombians.
AB  - INTRODUCTION: This study provides reference data and evaluates the potential of
      using regression models to predict maxillary and mandibular arch widths. METHODS:
      A total of 473 Colombian mestizos, aged 5 to 17 years, with normal occlusions and
      malocclusions (Class I and Class II Division 1) were evaluated. Arch widths and
      tooth sizes were measured on each subject's dental casts. Anthropometric
      measurements of body size, facial breadth, and facial height were used, along
      with tooth sizes, to develop multiple regressions for predicting arch widths.
      RESULTS: Analyses showed that Class II subjects had significantly (P < 0.05)
      narrower anterior maxillary widths than those with normal occlusion or Class I
      malocclusion. Class I subjects had narrower interpremolar widths than those with
      normal occlusion or Class II malocclusion. Boys had significantly (P < 0.001)
      wider arches than girls, especially in the posterior aspects. Older children had
      significantly wider arches than younger children, with intermolar and
      interpremolar widths having the largest and smallest age effects, respectively.
      Regression analyses of subjects with normal occlusion showed that 2 to 5
      variables combined to explain 36% to 64% of the variation in arch widths, with
      the sizes of the maxillary incisors and bigonial width explaining most of the
      variation. CONCLUSIONS: When applied to subjects with malocclusion, the
      predictions indicate transverse deficiencies in the premolar region of Class I
      subjects and deficiencies in the anterior maxilla of Class II subjects.
      Predictions based on Pont's index, the Schwarz analysis, or the McNamara rule of
      thumb were biased and less reliable than those based on the regressions.

PMID- 19409349
TI  - Quality of clinical photographs taken by orthodontists, professional
      photographers, and orthodontic auxiliaries.
AB  - INTRODUCTION: A survey of the members of the Angle Society of Europe showed that
      60% of orthodontists took their own clinical photographs, 35% assigned the task
      to an auxiliary, and 5% hired professional clinical photographers. It is always
      useful to ensure that orthodontists' time is used to maximum effect. Clinical
      photography could be delegated to auxiliary staff. In this study, we assessed the
      quality of photographs taken by orthodontists to see whether those taken by
      orthodontic auxiliaries and clinical photographers are of comparable quality.
      METHODS: Fifty sets of orthodontic photographs were collected from each of 3
      types of photographers: orthodontists, orthodontic auxiliaries, and professional
      clinical photographers. Four assessors scored each set for quality and detailed
      errors. The results were compared to determine whether there were differences
      between the quality of the photographs taken by the different groups. RESULTS AND
      CONCLUSIONS: Most of the photos taken by the 3 groups of photographers were
      judged to be good or acceptable. The results for extraoral photographs showed no
      statistically significant differences between the 3 groups for good (P = 0.398)
      and acceptable (P = 0.398) images. The results for intraoral photographs did not
      differ significantly for acceptable and unacceptable photographs, but
      orthodontists produced significantly more good-quality intraoral photographs (P =
      0.046).

PMID- 19409350
TI  - Treatment of a Class II subdivision malocclusion with multiple congenitally
      missing teeth.
AB  - This case report describes the treatment of a patient with a Class II Division 1
      subdivision right malocclusion with 8 congenitally missing teeth, incompetent
      lips, and incisor protrusion. The treatment plan included extractions and space
      closure with retraction of the anterior teeth; symmetric mechanics were used in
      the mandibular arch and asymmetric mechanics in the maxillary arch. Because of
      the mechanics used, some midline deviations were expected. Knowledge of diagnosis
      and treatment planning of asymmetric malocclusions and dental esthetics are
      essential for success when correcting asymmetic problems, but, even so, small
      clinical compromises should be expected.

PMID- 19409351
TI  - Combined use of miniscrews and clear appliances for the treatment of bialveolar
      protrusion without conventional brackets.
AB  - The increasing demand for esthetic orthodontic treatment has led to the
      development of tooth-colored and even "invisible" appliances. Although sequential
      removable clear aligners have several advantages over conventional bracket
      systems, they have some limitations in extraction treatment. This case report
      presents the esthetic extraction treatment of a patient with bialveolar
      protrusion; conventional brackets were not used. The treatment was completed in 2
      steps. The first step involved segmental retraction of the anterior teeth by
      using miniscrews and an anterior lingual splint with a clear lever arm. The
      second step involved alignment and finishing by using sequential removable clear
      aligners. The patient's esthetic demands were fulfilled successfully during
      treatment, and satisfactory facial profile and occlusion were achieved after
      treatment.

PMID- 19409352
TI  - Recent advances in cardiovascular risk reduction: implications of ONTARGET.
AB  - Renin-angiotensin-aldosterone system (RAAS) overactivity is associated with
      increased cardiovascular risk, a finding that may be explained by the key role of
      the RAAS in stimulating vascular and cardiac remodeling. Inhibition of RAAS
      activity with the use of angiotensin-converting enzyme (ACE) inhibitors or
      angiotensin II receptor blockers (ARBs) has been shown to reduce cardiovascular
      mortality in patients with heart failure. ACE inhibitors have also been shown to
      reduce the incidence of stroke, myocardial infarction (MI), and heart failure in
      high-risk patients without heart failure. These findings led to the evaluation of
      the ARB telmisartan versus the ACE inhibitor ramipril in the ONgoing Telmisartan
      Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), a
      cardioprotection trial conducted in high-risk patients without left ventricular
      dysfunction or heart failure. The results of this trial showed that the ACE
      inhibitor ramipril and the ARB telmisartan are equally effective in reducing the
      incidence of cardiovascular death, MI, stroke, and hospitalization for heart
      failure in patients without heart failure or left ventricular dysfunction but at
      high risk for cardiovascular disease (CVD). These results confirm that RAAS
      inhibition, using ACE inhibitors or ARBs, is an effective approach to reducing
      cardiovascular mortality and morbidity in patients without heart failure who are
      at high risk for CVD.

PMID- 19409353
TI  - The management and treatment of hypertension.
AB  - High blood pressure (HBP) is one of the most prevalent conditions seen today by
      clinicians, affecting an estimated 73 million--or 1 in 3--adult Americans, only
      one third of whom have achieved control of their hypertension (HBP). Central to
      the management of this pervasive medical condition are the issues of accurate
      diagnosis and maintaining control through appropriate treatment. Accurate
      diagnosis depends primarily on reliable measurement. Over the years, it has
      become increasingly recognized that blood pressure (BP) measurement occurring in
      clinical settings produces far less accurate and reliable readings than do other
      methods, notably 24-hour ambulatory BP monitoring and home BP measurement. Beyond
      technique, there are additional challenges to obtaining accurate readings,
      including emotional factors that produce either falsely elevated or lowered
      results, having the potential to mislead the clinician. The need to overcome
      obstacles to proper diagnosis and determine effective treatments has reached
      heightened urgency, especially for patients with compelling comorbidities such as
      diabetes, renal disease, congestive heart failure, and other cardiovascular
      diseases. The continuing evolution of the management of HBP is reflected in
      updated guidelines from the American Heart Association and evidence-based
      information stemming from recent studies and randomized clinical trials. The
      appropriate selection of antihypertensive agents, at the proper doses, is a
      complex issue requiring greater understanding of our pharmacologic options. The
      contributions of some of the more recent and salient studies and trials are
      mentioned here, although there is no attempt in this brief review to match drug
      classes with compelling indications. The trials discussed involve such
      pharmacologic treatments as diuretic therapy, alpha-blockers, conventional beta
      blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and
      angiotensin receptor blockers. Trial outcomes shed light on the relative benefits
      and drawbacks of these agents, often within the context of various patient
      characteristics such as age, comorbidities, and risk status. Successful
      management of HBP is a multi-faceted and ongoing endeavor, in which developing
      knowledge constantly tempered by new questions moves us toward the goal of
      improving the lives of our patients.

PMID- 19409354
TI  - Latest clinical developments in the diagnosis and treatment of hypertension.
      Introduction.

PMID- 19409355
TI  - Case study. ACE inhibitor-induced angioedema.

PMID- 19409356
TI  - The management of hypertension with angiotensin receptor blockers in special
      populations.
AB  - Angiotensin receptor blockers (ARBs) are the most recently approved major class
      of antihypertensive agents. The primary mechanism of action of ARBs is the
      selective blockade of the AT(1) receptor. There are 7 ARBs presently approved for
      clinical use in the United States, several with other indications in addition to
      blood pressure reduction in patients with hypertension. While ARBs appear to be
      no more potent than angiotensin-converting enzyme inhibitors for lowering blood
      pressure when used as monotherapy, they are a beneficial alternative and even
      compelling in certain populations. This class of agents also has the added
      benefit of placebo-like side effects, potentially enhancing adherence. In this
      review, studies are presented as positive evidence supporting the use of ARBs in
      special populations (including persons with diabetic nephropathy), in patients
      with heart failure (especially with systolic dysfunction), for cardioprotection
      in high-risk cardiac patients (including postmyocardial infarction and stroke),
      and for delaying new-onset diabetes. Clinical information on the effects of ARBs
      related to race and ethnicity are also discussed, although the data in most large
      trials are not substantial. Despite the fact that African American patients have
      the highest prevalence of hypertension (with increased mortality and morbidity),
      studies have been less robust regarding ARBs and protection against
      cardiovascular disease in this population. Although at least 1 major study has
      confirmed the benefit of ARBs in Asian patients with diabetic nephropathy,
      overall, treating patients based on race and ethnicity remains fraught with
      difficulty.

PMID- 19409357
TI  - Mind-body medicine: whose mind and whose body?

PMID- 19409358
TI  - The credit crunch for materialism.

PMID- 19409359
TI  - Mind-body medicine in clinical practice: challenges and opportunities.

PMID- 19409360
TI  - IOM Summit provides models for health reform.

PMID- 19409362
TI  - Abstracts of the 2009 North American Research Conference on Complementary and
      Integrative Medicine. May 12-15, 2009. Minneapolis, Minnesota, USA.

PMID- 19409361
TI  - Trends that will affect your future ... mind-body and the social dimension.
AB  - The SchwartzReport tracks emerging trends that will affect the world,
      particularly the United States. For EXPLORE, it focuses on matters of health in
      the broadest sense of that term, including medical issues, changes in the
      biosphere, technology, and policy considerations, all of which will shape our
      culture and our lives.

PMID- 19409363
TI  - The use of visual art for stress relief: a case report of newly diagnosed
      multiple sclerosis.

PMID- 19409364
TI  - Nutritional intervention in ADHD.

PMID- 19409365
TI  - Practicing healthy lifestyles.

PMID- 19409366
TI  - Functional medicine: theory, education, and practice.

PMID- 19409367
TI  - Dephosphorylation of photosystem II proteins and phosphorylation of CP29 in
      barley photosynthetic membranes as a response to water stress.
AB  - Kinetic studies of protein dephosphorylation in barley thylakoid membranes
      revealed accelerated dephosphorylation of photosystem II (PSII) proteins, and
      meanwhile rapidly induced phosphorylation of a light-harvesting complex (LHCII)
      b4, CP29 under water stress. Inhibition of dephosphorylation aggravates stress
      damages and hampers photosystem recovery after rewatering. This increased
      dephosphorylation is catalyzed by both intrinsic and extrinsic membrane protein
      phosphatase. Water stress did not cause any thylakoid destacking, and the lateral
      migration from granum membranes to stroma-exposed lamellae was only found to
      CP29, but not other PSII proteins. Activation of plastid proteases and release of
      TLP40, an inhibitor of the membrane phosphatases, were also enhanced during water
      stress. Phosphorylation of CP29 may facilitate disassociation of LHCII from PSII
      complex, disassembly of the LHCII trimer and its subsequent degradation, while
      general dephosphorylation of PSII proteins may be involved in repair cycle of
      PSII proteins and stress-response-signaling.

PMID- 19409368
TI  - Photo-catalytic oxidation of a di-nuclear manganese centre in an engineered
      bacterioferritin 'reaction centre'.
AB  - Photosynthesis involves the conversion of light into chemical energy through a
      series of electron transfer reactions within membrane-bound pigment/protein
      complexes. The Photosystem II (PSII) complex in plants, algae and cyanobacteria
      catalyse the oxidation of water to molecular O2. The complexity of PSII has thus
      far limited attempts to chemically replicate its function. Here we introduce a
      reverse engineering approach to build a simple, light-driven photo-catalyst based
      on the organization and function of the donor side of the PSII reaction centre.
      We have used bacterioferritin (BFR) (cytochrome b1) from Escherichia coli as the
      protein scaffold since it has several, inherently useful design features for
      engineering light-driven electron transport. Among these are: (i.) a di-iron
      binding site; (ii.) a potentially redox-active tyrosine residue; and (iii.) the
      ability to dimerise and form an inter-protein heme binding pocket within electron
      tunnelling distance of the di-iron binding site. Upon replacing the heme with the
      photoactive zinc-chlorin e6 (ZnCe6) molecule and the di-iron binding site with
      two manganese ions, we show that the two Mn ions bind as a weakly coupled di
      nuclear Mn2II,II centre, and that ZnCe6 binds in stoichiometric amounts of 1:2
      with respect to the dimeric form of BFR. Upon illumination the bound ZnCe6
      initiates electron transfer, followed by oxidation of the di-nuclear Mn centre
      possibly via one of the inherent tyrosine residues in the vicinity of the Mn
      cluster. The light dependent loss of the MnII EPR signals and the formation of
      low field parallel mode Mn EPR signals are attributed to the formation of MnIII
      species. The formation of the MnIII is concomitant with consumption of oxygen.
      Our model is the first artificial reaction centre developed for the photo
      catalytic oxidation of a di-metal site within a protein matrix which potentially
      mimics water oxidation centre (WOC) photo-assembly.

PMID- 19409369
TI  - Protein-cofactor interactions in bioenergetic complexes: the role of the A1A and
      A1B phylloquinones in Photosystem I.
AB  - This review focuses on phylloquinone as an indispensable link between light
      induced charge separation and subsequent charge stabilization in Photosystem I
      (PS I). Here, the role of the polypeptide in conferring the necessary kinetic and
      thermodynamic properties to phylloquinone so as to specify its functional role in
      PS I electron transfer is discussed. Photosynthetic electron transfer and the
      role of quinones in Type I and Type II reaction centers are introduced at the
      outset with particular emphasis on the determination of redox potentials of the
      cofactors. Currently used methodologies, particularly time-resolved optical
      spectroscopy and varieties of magnetic resonance spectroscopy that have become
      invaluable in uncovering the details of phylloquinone function are described in
      depth. Recent studies on the selective alteration of the protein environment and
      on the incorporation of foreign quinones either by chemical or genetic means are
      explored to assess how these studies have improved our understanding of protein
      quinone interactions. Particular attention is paid to the function of the H-bond,
      methyl group and phytyl tail of the phylloquinone in interacting with the protein
      environment.

PMID- 19409370
TI  - Evidence of pores and thinned lipid bilayers induced in oriented lipid membranes
      interacting with the antimicrobial peptides, magainin-2 and aurein-3.3.
AB  - Dynamic structures of supramolecular lipid assemblies, such as toroidal pores and
      thinned bilayers induced in oriented lipid membranes, which are interacting with
      membrane-acting antimicrobial peptides (AMPs), magainin-2 and aurein-3.3, were
      explored by 31P and 2H solid-state NMR (ssNMR) spectroscopy. Various types of
      phospholipid systems, such as POPC-d31, POPC-d31/POPG, and POPC-d31/cholesterol,
      were investigated to understand the membrane disruption mechanisms of magainin-2
      and aurein-3.3 peptides at various peptide-to-lipid (P:L) ratios. The
      experimental lineshapes of anisotropic 31P and 2H ssNMR spectra measured on these
      peptide-lipid systems were simulated reasonably well by assuming the presence of
      supramolecular lipid assemblies, such as toroidal pores and thinned bilayers, in
      membranes. Furthermore, the observed decrease in the anisotropic frequency span
      of either 31P or 2H ssNMR spectra of oriented lipid bilayers, particularly when
      anionic POPG lipids are interacting with AMPs at high P:L ratios, can directly be
      explained by a thinned membrane surface model with fast lateral diffusive motions
      of lipids. The spectral analysis protocol we developed enables extraction of the
      lateral diffusion coefficients of lipids distributed on the curved surfaces of
      pores and thinned bilayers on a few nanometers scale.

PMID- 19409371
TI  - A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer
      growth.
AB  - Overexpression of ErbB2 in breast cancer is associated with increased recurrence
      and worse prognosis. Accumulating evidences suggest that molecular targeted
      therapy is a promising anticancer strategy. In this study, we produced a novel
      anti-ErbB2 monoclonal antibody, 6G10, that recognized an epitope distinct from
      the trastuzumab binding site. 6G10 induced aggregation of BT474 breast cancer
      cells and inhibited proliferation of various breast cancer cell lines including
      BT474. A growth inhibition assay showed that 6G10 had EC(50) values comparable to
      trastuzumab, indicating that the drugs have a similar level of potency.
      Furthermore, intraperitoneal administration of 6G10 completely inhibited the
      growth of xenografted tumors derived from BT474 and SK-BR-3 cells. These data
      suggested that 6G10 has great therapeutic potential and could be administered to
      patients alternatively, or synergistically, with trastuzumab.

PMID- 19409372
TI  - Overexpression of Midkine promotes the viability of BA/F3 cells.
AB  - Midkine (MK), a heparin-binding growth factor, has been reported to be
      overexpressed in a variety of human solid tumors. In the previous study, we found
      that MK was overexpressed in bone marrow samples derived from acute leukemia (AL)
      patients. To elucidate the role of MK, we stably transfected MK in IL-3-dependent
      BA/F3 cells. The results indicated that the capacity of proliferation and colony
      formation was significantly increased in the MK-transfected subclones than in the
      empty vector-transfected subclones. MK potentiated proliferation of BA/F3 cells
      by promoting cell cycle progression. Apoptosis assays showed a remarkable
      reduction of apoptosis in MK expressing subclones. Exogenous MK could induce the
      phosphorylation of Raf-1, and inhibit the expression of Bax in BA/F3 cells. These
      results indicate that MK might be involved in the pathogenesis of leukemia and
      could be taken as an ideal diagnostic marker and molecular target for the
      treatment of acute leukemia.

PMID- 19409373
TI  - Thromboxane prostanoid receptor activation impairs endothelial nitric oxide
      dependent vasorelaxations: the role of Rho kinase.
AB  - Activation of thromboxane prostanoid (TP) receptors causes potent
      vasoconstriction, which contributes to increased vascular tone and blood
      pressure. The present study examined the hypothesis that stimulation of TP
      receptor impaired endothelial nitric oxide-mediated vasorelaxation via a Rho
      kinase-dependent mechanism. The common carotid arteries of Sprague-Dawley rats
      were isolated and suspended in myograph for measurement of changes in isometric
      tension. The production of nitric oxide in primary cultured aortic endothelial
      cells was assayed with an imaging technique and phosphorylated levels of
      endothelial NOS were determined by Western blot analysis. 9,11-dideoxy
      11alpha,9alpha-epoxy-methanoprostaglandin F(2alpha) (U46619) inhibited
      isoprenaline-induced relaxations in rings with or without endothelium. Treatment
      with Rho kinase inhibitors, Y27632 (2 microM) or HA 1077 (10 microM) prevented
      the effect of U46619 only in rings with endothelium while protein kinase C
      inhibitors were without effect. Rho kinase inhibitors did not affect isoprenaline
      induced relaxations in endothelium-intact rings treated with L-NAME or 1H
      [1,2,4]oxadizolo[4,3-a]quinoxalin-1-one (ODQ). Isoprenaline stimulated rises in
      nitric oxide (NO) production in cultured rat endothelial cells. The increased NO
      production was inhibited by U46619 (100 nM) and this effect was prevented by
      treatment with Y27632 but unaffected by the absence of extracellular calcium
      ions. U46619 attenuated isoprenaline-stimulated phosphorylation of eNOS, which
      was sensitive to inhibition by Y27632 and HA 1077. U46619-mediated effects were
      abolished by TP receptor antagonist, S18886 and the TP receptor was present in
      endothelial cells. The present results demonstrate that Rho kinase activation is
      likely to be the primary mechanism that underlies the U46619-stimulated TP
      receptor-mediated inhibition of endothelial NO production and subsequent
      endothelium-dependent relaxations to isoprenaline.

PMID- 19409374
TI  - Reduced skin inflammatory response in mice lacking inducible nitric oxide
      synthase.
AB  - The skin is the largest organ in the body and one of its main functions is to
      protect the body from environmental and endogenous noxious conditions, such as
      injury, infection and inflammation. The inducible nitric oxide synthase (iNOS)
      has been implicated as a key component in the inflammatory response. In the
      present study, we assessed the role of iNOS in the skin inflammation induced by
      12-O-tetradecanoylphorbol-13-acetate (TPA). Mice deficient in iNOS had reduced
      edema and cellular infiltration in the skin following topical TPA application.
      Moreover, the genetic blockage of iNOS signaling inhibited the TPA-induced ERK
      and p38 activation resulting in reduced COX-2 upregulation. Finally,
      immunohistochemical studies revealed that iNOS knockout mice exhibited marked
      inhibition of AP-1, CREB and NF-kappaB transcriptional factors activation.
      Together, these results indicate that TPA induces the activation of several iNOS
      dependent intracellular signaling pathways that have a key role in the control of
      inflammatory response in the skin. Therefore, selective iNOS inhibitors may be
      potentially relevant tools for cutaneous skin disease drug development.

PMID- 19409375
TI  - Clozapine inhibits strychnine-sensitive glycine receptors in rat hippocampal
      neurons.
AB  - Seizure is one kind of severe side effects during clozapine (Clo) treatment.
      However, the mechanism of seizure associated with Clo therapy is not completely
      clear. Strychnine-sensitive glycine receptors (GlyRs) play an important role in
      regulating the excitability in the hippocampus. In the present study, we
      investigated the effect of Clo on GlyRs in cultured hippocampal neurons of rats.
      Clo reversibly inhibited the glycine-induced chloride currents (I(Gly)) in a
      concentration-dependent manner. The half-maximal effect concentration (EC(50))
      for glycine alone was 25.6+/-0.7 microM with the Hill coefficient 1.5+/-0.1; in
      the presence of Clo, the EC(50) and the Hill coefficient were 28.9+/-6.3 microM
      and 1.2+/-0.3 respectively, which were not significantly affected by Clo. In
      addition, Clo inhibition of I(Gly) was not influenced by blocking D(1) and D(2)
      dopamine receptors with haloperidol (Hal). Taken together, these results suggest
      that Clo is a non-competitive antagonist of GlyR independent of its activation of
      dopamine receptors, which may contribute to seizure associated with Clo therapy.

PMID- 19409376
TI  - Short-term (2 to 5 h) dark exposure lowers long-term potentiation (LTP) induction
      threshold in rat primary visual cortex.
AB  - Up- and down-regulation of synaptic strength (i.e., long-term potentiation, LTP,
      long-term depression) is thought to be the primary mechanism mediating experience
      dependent plasticity of cortical networks. Recent evidence indicates that the
      expression of plastic changes at synapses itself is dynamic and regulated, at
      least in part, by the recent history of synaptic activity, a concept termed
      metaplasticity. Here, adult, urethane-anesthetized rats were exposed to light or
      dark conditions for various durations (1, 2, and 5 h) to influence activity
      levels in the retinal-dorsal lateral geniculate nucleus (dLGN)-primary visual
      cortex (V1) pathway. Field potentials, recorded in layer IV of V1, were evoked by
      light flashes to the retina or single pulse electrical stimulation of the dLGN.
      Brief (60 s) periods of high frequency (50 Hz) retinal light stimulation results
      in an increase in visual evoked potential (VEP) amplitude in animals exposed to
      complete darkness for 2 h, while VEP amplitude failed to show potentiation in
      animals maintained in darkness for shorter periods. Similarly, weak theta burst
      stimulation of the dLGN failed to induce LTP in animals maintained under
      continuous light, but elicited robust LTP after 5 h of dark exposure. These data
      demonstrate that induction thresholds for sensory- and electrically-induced LTP
      in the retino-geniculo-cortical pathway of adult rats are dynamically regulated
      by levels of preceding sensory stimulation. Importantly, such metaplastic
      adjustments of plasticity in V1 can occur over time-scales significantly shorter
      than previously recognized.

PMID- 19409377
TI  - Phenotype determination of hemoglobinopathies by mass spectrometry.
AB  - OBJECTIVES: Nowadays, nearly 1000 hemoglobin (Hb) variants are known. The
      standard biochemical techniques used in Hb analysis are mainly: isoelectric
      focusing, cation-exchange liquid chromatography (LC) and reversed-phase LC. In
      addition to this approach, a protein analysis is achieved by mass spectrometry
      (MS) and additional DNA studies are performed. The aim of this review is to
      emphasize the significance of MS methods applied to Hb variants analysis. RESULTS
      AND PERSPECTIVES: To perform Hb studies, different MS techniques are currently
      used such as electrospray ionization (ESI), matrix-assisted laser desorption
      ionization (MALDI) and tandem mass spectrometry (MS/MS). As shown here, MS is an
      efficient tool for identification of all types of variants (substitution of a
      single amino acid residue, several substitutions in the same globin chain,
      insertions/deletions, fusion Hbs). The use of MS in neonatal screening of Hb
      variants is also presented. CONCLUSIONS: MS is a powerful technique for Hb
      analysis. It appears as being an important additional method in the set of
      biochemical techniques.

PMID- 19409378
TI  - Quantitative analysis of epithelial morphogenesis in Drosophila oogenesis: New
      insights based on morphometric analysis and mechanical modeling.
AB  - The process of epithelial morphogenesis is ubiquitous in animal development, but
      much remains to be learned about the mechanisms that shape epithelial tissues.
      The follicle cell (FC) epithelium encapsulating the growing germline of
      Drosophila is an excellent system to study fundamental elements of epithelial
      development. During stages 8 to 10 of oogenesis, the FC epithelium transitions
      between simple geometries-cuboidal, columnar and squamous-and redistributes cell
      populations in processes described as posterior migration, squamous cell
      flattening and main body cell columnarization. Here we have carried out a
      quantitative morphometric analysis of these poorly understood events in order to
      establish the parameters of and delimit the potential processes that regulate the
      transitions. Our results compel a striking revision of accepted views of these
      phenomena, by showing that posterior migration does not involve FC movements,
      that there is no role for columnar cell apical constriction in FC morphogenesis,
      and that squamous cell flattening may be a compliant response to germline growth.
      We utilize mechanical modeling involving finite element computational
      technologies to demonstrate that time-varying viscoelastic properties and growth
      are sufficient to account for the bulk of the FC morphogenetic changes.

PMID- 19409380
TI  - Loss of Drp1 function alters OPA1 processing and changes mitochondrial membrane
      organization.
AB  - RNAi mediated loss of Drp1 function changes mitochondrial morphology in cultured
      HeLa and HUVEC cells by shifting the balance of mitochondrial fission and fusion
      towards unopposed fusion. Over time, inhibition of Drp1 expression results in the
      formation of a highly branched mitochondrial network along with "bulge"-like
      structures. These changes in mitochondrial morphology are accompanied by a
      reduction in levels of Mitofusin 1 (Mfn1) and 2 (Mfn2) and a modified proteolytic
      processing of OPA1 isoforms, resulting in the inhibition of cell proliferation.
      In addition, our data imply that bulge formation is driven by Mfn1 action along
      with particular proteolytic short-OPA1 (s-OPA1) variants: Loss of Mfn2 in the
      absence of Drp1 results in an increase of Mfn1 levels along with processed s-OPA1
      isoforms, thereby enhancing continuous "fusion" and bulge formation. Moreover,
      bulge formation might reflect s-OPA1 mitochondrial membrane remodeling activity,
      resulting in the compartmentalization of cytochrome c deposits. The proteins
      Yme1L and PHB2 appeared not associated with the observed enhanced OPA1
      proteolysis upon RNAi of Drp1, suggesting the existence of other OPA1 processing
      controlling proteins. Taken together, Drp1 appears to affect the activity of the
      mitochondrial fusion machinery by unbalancing the protein levels of mitofusins
      and OPA1.

PMID- 19409379
TI  - The role of hERG1 K+ channels and a functional link between hERG1 K+ channels and
      SDF-1 in acute leukemic cell migration.
AB  - Stromal cell-derived factor-1 (SDF-1) and its unique receptor, CXCR4, regulate
      stem/progenitor cell migration and retention in the bone marrow and are required
      for hematopoiesis. Recent studies found that hERG1 K(+) channels were important
      regulators of tumor cell migration. In this study, we investigated whether SDF-1
      induced acute leukemic cell migration associated with hERG1 K(+) channels. Our
      results showed that E-4031, a specific hERG1 K(+) channels inhibitor,
      significantly blocked SDF-1-induced migration of leukemic cell lines, primary
      acute leukemic cells, leukemic stem cells and HEK293T cells transfected with herg
      pEGFP. The migration of phenotypically recognizable subsets gave the indication
      that lymphoblastic leukemic cells were inhibited more than myeloid cells while in
      the presence of E-4031 which maybe associated with herg expression. SDF-1
      increased hERG1 K(+) current expressed in oocytes and HEK293T cells transfected
      with herg-pEGFP. There were no significant changes of CXCR4 expression on both HL
      60 cells and primary leukemic cells regardless if untreated or treated with E
      4031 for 24 h (P>0.05). The hERG1 K(+) current increased by SDF-1 might
      contribute to the mechanism of SDF-1-induced leukemic cell migration. The data
      suggested that hERG1 K(+) channels functionally linked to cell migration induced
      by SDF-1.

PMID- 19409381
TI  - Compartmentalized microfluidic culture platform to study mechanism of paclitaxel
      induced axonal degeneration.
AB  - Chemotherapy induced peripheral neuropathy is a common and dose-limiting side
      effect of anticancer drugs. Studies aimed at understanding the underlying
      mechanism of neurotoxicity of chemotherapeutic drugs have been hampered by lack
      of suitable culture systems that can differentiate between neuronal cell body,
      axon or associated glial cells. Here, we have developed an in vitro
      compartmentalized microfluidic culture system to examine the site of toxicity of
      chemotherapeutic drugs. To test the culture platform, we used paclitaxel, a
      widely used anticancer drug for breast cancer, because it causes sensory
      polyneuropathy in a large proportion of patients and there is no effective
      treatment. In previous in vitro studies, paclitaxel induced distal axonal
      degeneration but it was unclear if this was due to direct toxicity on the axon or
      a consequence of toxicity on the neuronal cell body. Using microfluidic channels
      that allow compartmentalized culturing of neurons and axons, we demonstrate that
      the axons are much more susceptible to toxic effects of paclitaxel. When
      paclitaxel was applied to the axonal side, there was clear degeneration of axons;
      but when paclitaxel was applied to the soma side, there was no change in axon
      length. Furthermore, we show that recombinant human erythropoietin, which had
      been shown to be neuroprotective against paclitaxel neurotoxicity, provides
      neuroprotection whether it is applied to the cell body or the axons directly.
      This observation has implications for development of neuroprotective drugs for
      chemotherapy induced peripheral neuropathies as dorsal root ganglia do not
      possess blood-nerve-barrier, eliminating one of the cardinal requirements of drug
      development for the nervous system. This compartmentalized microfluidic culture
      system can be used for studies aimed at understanding axon degeneration,
      neuroprotection and development of the nervous system.

PMID- 19409382
TI  - Sleep deprivation attenuates inflammatory responses and ischemic cell death.
AB  - Although the biological function of sleep remains uncertain, the consequences of
      sleep deprivation are well-described and are reported to be detrimental to
      cognitive function and affective well-being. Sleep deprivation also is strongly
      associated with elevated risk factors for cardiovascular disease. We used a mouse
      model of cardiac arrest/cardiopulmonary resuscitation to test the hypothesis that
      acute sleep deprivation would exacerbate neuroinflammation and neurodegeneration
      after global ischemia. The resulting data led to a rejection of our hypothesis
      that sleep deprivation is necessarily detrimental. Indeed, acute sleep
      deprivation (ASD) was associated with a reduction in ischemia-induced interleukin
      1beta (IL-1beta) gene expression and attenuation of neuronal damage in the
      hippocampus. Further, sleep deprivation increased gene expression of two anti
      inflammatory cytokines, IL-6 and IL-10 that are associated with improved ischemic
      outcome. To determine whether the anti-inflammatory properties of ASD were
      specific to ischemia, mice were treated systemically with lipopolysaccharide
      (LPS), a potent inflammogen. Acute sleep deprivation attenuated the central and
      peripheral increase in tumor necrosis factor-alpha (TNFalpha) and increased IL-10
      expression. Together, the ischemia and LPS data suggest that, ASD produces an
      anti-inflammatory bias that could be exploited to improve medical procedures that
      are compromised by inflammation.

PMID- 19409383
TI  - Repetitive transcranial magnetic stimulation of the prefrontal cortex in
      depression.
AB  - Transcranial magnetic stimulation is an interesting technique for non-invasively
      stimulating the brain in awake alert humans. It is a powerful research tool for
      examining brain behavior relationships. Additionally many researchers are
      investigating whether repeatedly applying TMS to specific regions over several
      days to weeks might have therapeutic effects. By far the largest amount of work
      has been done investigating whether daily applications of prefrontal TMS can
      improve the symptoms of major depression. We review the literature combining TMS
      with brain imaging, and then overview the clinical work done to date with TMS in
      depression. The literature to date suggests that daily prefrontal TMS for several
      weeks clearly has antidepressant effects, but much work remains to establish the
      effect sizes and improve the methods of delivery in order to improve its
      potential clinical utility.

PMID- 19409384
TI  - PAK kinase regulates Rac GTPase and is a potential target in human schwannomas.
AB  - Merlin loss causes benign tumours of the nervous system, mainly schwannomas and
      meningiomas. Schwannomas show enhanced Rac1 and Cdc42 activity, the p21-activated
      kinase 2 (PAK2) activation and increased ruffling and cell adhesion. PAK
      regulates activation of merlin. PAK has been proposed as a potential therapeutic
      target in schwannomas. However where PAK stands in the Rac pathway is
      insufficiently characterised. We used a novel small-molecule PAK inhibitor, IPA
      3, to investigate the role of PAK activation on Rac1/Cdc42 activity, cell
      spreading and adhesion in human primary schwannoma and Schwann cells. We show
      that IPA-3 blocks activation of PAK2 at Ser192/197 that antagonises PAK's
      interaction with Pix. Accordingly, Pix-mediated Rac1 activation is decreased in
      IPA-3 treated schwannoma cells, indicating that PAK acts upstream of Rac. We show
      that this Rac activation at the level of focal adhesions in schwannoma cells is
      essential for cell spreading and adhesion in Schwann and schwannoma cells.

PMID- 19409386
TI  - The role of N-glycosylation in transport function and surface targeting of the
      human solute carrier PAT1.
AB  - In the present study we show in the Xenopus laevis expression system that the
      proton-coupled amino acid transporter 1 (PAT1, SLC36A1) is glycosylated at
      asparagine residues N174, N183 and N470. To determine the functional role of N
      glycosylation, glycosylation-deficient mutants were analyzed by two-electrode
      voltage-clamp measurements after expression in X. laevis oocytes. Single
      replacements of asparagine residues had no effect on transport activity. However,
      multiple substitutions resulted in a decreased transport rate, leaving K(t)
      unchanged. Immunofluorescence localisation revealed a diminished plasma membrane
      expression of glycosylation-defective mutants. This indicates that N-glycans are
      not required for transport function, but are important for membrane targeting.

PMID- 19409387
TI  - Does distant homology with Evf reveal a lipid binding site in Bacillus
      thuringiensis cytolytic toxins?
AB  - The Cry and Cyt classes of insecticidal toxins derived from the sporulating
      bacterium Bacillus thuringiensis are valuable substitutes for synthetic
      pesticides in agricultural contexts. Crystal structures and many biochemical data
      have provided insights into their molecular mechanisms, generally thought to
      involve oligomerization and pore formation, but have not localised the site on
      Cyt toxins responsible for selective binding of phospholipids containing
      unsaturated fatty acids. Here, distant homology between the structure of Cyt
      toxins and Erwinia virulence factor (Evf) is demonstrated which, along with
      sequence conservation analysis, allows a putative lipid binding site to be
      localised in the toxins.

PMID- 19409385
TI  - Translocator protein (18 kDa) TSPO: an emerging therapeutic target in
      neurotrauma.
AB  - Traumatic brain injury (TBI) induces physical, cognitive, and psychosocial
      deficits that affect millions of patients. TBI activates numerous cellular
      mechanisms and molecular cascades that produce detrimental outcomes, including
      neuronal death and loss of function. The mitochondrion is one of the major
      targets of TBI, as seen by increased mitochondrial activity in activated and
      proliferating microglia (due to high energy requirements and/or calcium overload)
      as well as increased reactive oxygen species, changes in mitochondrial
      permeability transition, release of cytochrome c, caspase activation, reduced ATP
      levels, and cell death in neurons. Translocator protein (TSPO) is an 18-kDa outer
      mitochondrial membrane protein that interacts with the mitochondria permeability
      transition pore and binds with high affinity to cholesterol and various classes
      of drug ligands, including some benzodiazepines such as 4'-chlorodiazepam (Ro5
      4864). Although TSPO levels in the brain are low, they are increased after brain
      injury and inflammation. This finding has led to the proposed use of TSPO
      expression as a marker of brain injury and repair. TSPO drug ligands have been
      shown to participate in the control of mitochondrial respiration and function,
      mitochondrial steroid and neurosteroid formation, as well as apoptosis. This
      review and commentary will outline our current knowledge of the benefits of
      targeting TSPO for TBI treatment and the mechanisms underlying the
      neuroprotective effects of TSPO drug ligands in neurotrauma.

PMID- 19409388
TI  - Isolation and characterization of cytoplasmic cyclin D1 mutants.
AB  - To elucidate the mechanism governing the subcellular distribution of cyclin D1
      protein, we randomly mutagenized human cyclin D1 cDNA and isolated mutants that
      encode the protein predominantly located in the cytoplasm. Experiments with
      Leptomycin B suggested a defect in transportation from the cytoplasm to the
      nucleus rather than enhanced nuclear exportation. Sequencing revealed that the
      mutations responsible for the cytoplasmic localization of cyclin D1 resided in
      the vicinity of the cyclin box, which affected interaction with a catalytic
      partner, Cdk4. We propose that interaction between cyclin D1 and Cdk4 triggers
      the mechanism controlling the nuclear transportation of this kinase complex.

PMID- 19409390
TI  - Fluoxetine potentiates the effects of corticotropin-releasing factor on locomotor
      activity and serotonergic systems in the roughskin newt, Taricha granulosa.
AB  - The anxiety- and stress-related neuropeptide corticotropin-releasing factor (CRF)
      elicits behavioral changes in vertebrates including increases in behavioral
      arousal and locomotor activity. Intracerebroventricular injections of CRF in an
      amphibian, the roughskin newt (Taricha granulosa), induces rapid increases in
      locomotor activity in both intact and hypophysectomized animals. We hypothesized
      that this CRF-induced increase in locomotor activity involves a central effect of
      CRF on serotonergic neurons, based on known stimulatory actions of serotonin (5
      hydroxytryptamine, 5-HT) on spinal motor neurons and the central pattern
      generator for locomotor activity in vertebrates. In Experiment 1, we found that
      neither intracerebroventricular injections of low doses of CRF (25 ng) nor the
      selective serotonin reuptake inhibitor fluoxetine (10, 100 ng), by themselves,
      altered locomotor activity. In contrast, newts treated concurrently with CRF and
      fluoxetine responded with marked increases in locomotor activity. In Experiment
      2, we found that increases in locomotor activity following co-administration of
      CRF (25 ng) and fluoxetine (100 ng) were associated with decreased 5-HT
      concentrations in a number of forebrain structures involved in regulation of
      emotional behavior and emotional states, including the ventral striatum, amygdala
      pars lateralis, and dorsal hypothalamus, measured 37 min after treatment. These
      results are consistent with the hypothesis that CRF stimulates locomotor activity
      through activation of serotonergic systems.

PMID- 19409389
TI  - Urotensin I-CRF-Urocortins: a mermaid's tail.
AB  - From the individual perspective of the two authors who were long-time colleagues
      of Karl Lederis at the University of Calgary, the events and personal
      interactions are described, that are relevant to the discovery of Urotensin I
      (UI) in the Lederis laboratory, along with the concurrent discovery of Urotensin
      II (UII) in the Bern laboratory and corticotropin-releasing factor (CRF/CRH) in
      the Vale laboratory. The fortuitous sabbatical experiences that put Professors
      Lederis and Bern on the track of the Urotensins, along with the essential
      isolation paradigm that resulted in the complete sequencing and synthesis of UI
      and UII are summarized. The chance interaction between Drs. Vale and Lederis who,
      prior to the publications of the sequences of UI and CRF, realized the sequence
      commonalities of these peptides with the vasoactive frog peptide, sauvagine, is
      outlined. Further, the relationship between the pharmacological studies done with
      UI in the Calgary laboratory and the more recent understanding of the biology and
      receptor pharmacology for the entire Urotensin I-CRF-Urocortin peptide family is
      dealt with. The value of a comparative endocrinology approach to understanding
      hormone action is emphasized, along with a projection to the future, based on new
      hypotheses that can be generated by unexplained data already in the literature.
      Based on the previously described pharmacology of the UI-CRF-Urocortin peptides
      in a number of target tissues, it is suggested that the use of current molecular
      approaches can be integrated with a 'classical' pharmacological approach to
      generate new insights about the UI-CRF-Urocortin hormone family.

PMID- 19409391
TI  - Age-dependent plasticity of sex pheromone response in the moth, Agrotis ipsilon:
      combined effects of octopamine and juvenile hormone.
AB  - Male moths use sex pheromones to find their mating partners. In the moth, Agrotis
      ipsilon, the behavioral response and the neuron sensitivity within the primary
      olfactory centre, the antennal lobe (AL), to sex pheromone increase with age and
      juvenile hormone (JH) biosynthesis. By manipulating the JH level, we previously
      showed that JH controls this age-dependent neuronal plasticity, and that its
      effects are slow (within 2 days). We hypothesized that the hormonal effect might
      be indirect, and one neuromodulator candidate, which might serve as a mediator,
      is octopamine (OA). Here, we studied the effects of OA and an OA receptor
      antagonist, mianserin, on behavioral and AL neuron responses of mature and
      immature males during stimulation with sex pheromone. Our results indicate that,
      although OA injections enhanced the behavioral pheromone response in mature
      males, OA had no significant effect on behavior in immature males. However,
      mianserin injections decreased the behavioral response in mature males. AL neuron
      sensitivity increased after OA treatment in immature males, and decreased after
      mianserin treatment in mature males. Determination of OA levels in ALs of
      immature and mature males did not reveal any difference. To study the possible
      interactive effects of JH and OA, the behavioral pheromone response was analyzed
      in JH-deprived mature males injected with OA, and in immature males injected with
      fenoxycarb, a JH agonist, and mianserin. Results show that both JH and OA are
      necessary to elicit a behavioral response of A. ipsilon males to sex pheromone.

PMID- 19409392
TI  - Are gonadal steroids linked with orgasm perceptions and sexual assertiveness in
      women and men?
AB  - Past findings suggest links between orgasms and testosterone (T), as well as
      sexuality and estradiol (E), and we examined hormone-orgasm links in this study
      via two hypotheses (below). Participants were 86 women and 91 men who provided a
      saliva sample and completed a demographics questionnaire, the Orgasm Checklist
      (Mah and Binik, 2002), the Hurlbert (1991) Index of Sexual Assertiveness, and the
      Sexual Desire Inventory (Spector and Fremeth, 1996). Results supported the first
      hypothesis of correlations between T and positive orgasm experience in women,
      specifically with the relaxation, soothing, and peaceful items in both partnered
      and solitary orgasm contexts. Results also indicated correlations between E and
      flooding and spreading items in a solitary orgasm context. There were no
      associations between hormones and men's perceptions of their orgasm experiences.
      There was no support for the second hypothesis of associations between higher T
      and more sexual assertiveness. Post hoc analyses showed associations between E
      and women's sexual desire, and T and men's sexual desire. We discuss implications
      of these findings including that solitary vs. partnered orgasm experiences may
      differ, and suggest that T might be associated with perceptions of psychological
      experiences of orgasms, and E might be associated with perceptions of physical
      experiences of orgasms.

PMID- 19409393
TI  - The probable significance of tracheal tufts in the 8th abdominal segment of
      Heliothis virescens (F.) on the development of its parasitoid, Toxoneuron
      nigriceps (Viereck).
AB  - The 8th abdominal segment of Heliothis virescens (Fabricius) larvae contains
      aerating trachea and tracheole tufts that end in the hemocoel of the 8th segment,
      unlike the tracheae that invade tissues in other segments. These tracheal tufts
      from the 8th abdominal segment extend to the tokus region, which along with the
      telson cavity is known to act as a "lung" for hemocytes in Calpodes ethlius and a
      few other lepidopteran larvae. The goal of this research was to study the effects
      of these tracheal tufts in the 8th abdominal segment on parasitoid development
      inside the host larvae, H. virescens. The first objective was to determine if the
      eggs of the parasitoid, Toxoneuron nigriceps, are predominantly located among the
      tracheal tufts of the 8th abdominal segment compared to other body cavity regions
      irrespective of their oviposition site or the position of the host larvae. The
      results showed that several hours after oviposition most of the eggs are found in
      the 8th abdominal segment irrespective of the oviposition site or the position of
      the host larvae. The second objective was to study the effect of varying oxygen
      concentrations in vitro on various developmental stages of the egg. The results
      showed that decreasing oxygen concentrations adversely affects the parasitoid egg
      development in vitro. A third objective was to determine the oxygen concentration
      in 8th abdominal segment of the host larvae and compare it to other regions of
      the body using an oxygen sensor placed in vivo. The results suggested relatively
      high concentration of oxygen in the 8th abdominal segment compared to other
      regions of the host, thus supporting our hypothesis that the increased oxygen
      level in the 8th abdominal segment is important to the development of the
      parasitoid eggs.

PMID- 19409394
TI  - Interaction surface of bacteriophage P4 protein Psu required for complex
      formation with the transcription terminator Rho.
AB  - Rho-dependent transcription termination is an essential function in prokaryotes,
      and the transcription terminator Rho is highly conserved among different species.
      The bacteriophage P4 capsid-decoration protein, Psu, interacts specifically with
      and inhibits the function of Escherichia coli Rho. The interaction surface of Psu
      involved in interacting with Rho is not known, but knowledge of this is important
      to understand the mechanism of its action and will be useful to design peptide
      inhibitor(s) for Rho. We have isolated and characterized seven Psu mutants
      defective in interacting with Rho and in exerting anti-Rho activity.
      Conformational probing of Psu revealed that the N-terminal region of the protein
      folds over onto its central part, forming a globular domain and leaving a solvent
      exposed "tail" in the C-terminus. The mutations are located in both of these
      domains. N-terminal mutants are instrumental in disrupting the N- to C-terminal
      "cross-talk" in Psu that is required for its structural integrity and its
      function. Site-specific cross-linking experiments showed that the C-terminal tail
      preferentially cross-links to Rho and this region of Psu is protected from
      limited proteolysis when bound to Rho. Therefore, the mutations in this region
      may have affected the direct interaction of Psu with Rho. We propose that the
      globular N-terminal domain of Psu confers structural integrity to the
      functionally important C-terminal tail, which interacts directly with the
      hexameric Rho.

PMID- 19409395
TI  - More than a simple lipophilic contact: a detailed thermodynamic analysis of
      nonbasic residues in the s1 pocket of thrombin.
AB  - The field of medicinal chemistry aims to design and optimize small molecule leads
      into drug candidates that may positively interfere with pathological disease
      situations in humans or combat the growth of infective pathogens. From the
      plethora of crystal structures of protein-inhibitor complexes we have learned how
      molecules recognize each other geometrically, but we still have rather
      superficial understanding of why they bind to each other. This contribution
      surveys a series of 26 thrombin inhibitors with small systematic structural
      differences to elucidate the rationale for their widely deviating binding
      affinity from 185 microM to 4 nM as recorded by enzyme kinetic measurements. Five
      well-resolved (resolution 2.30 - 1.47 A) crystal structures of thrombin-inhibitor
      complexes and an apo-structure of the uncomplexed enzyme (1.50 A) are correlated
      with thermodynamic data recorded by isothermal titration calorimetry with 12
      selected inhibitors from the series. Taking solubility data into account, the
      variation in physicochemical properties allows conclusions to be reached about
      the relative importance of the enthalpic binding features as well as to estimate
      the importance of the parameters more difficult to capture, such as residual
      ligand entropy and desolvation properties. The collected data reveal a
      comprehensive picture of the thermodynamic signature that explains the so far
      poorly understood attractive force experienced by m-chloro-benzylamides to
      thrombin.

PMID- 19409396
TI  - Gamma-turn types prediction in proteins using the two-stage hybrid neural
      discriminant model.
AB  - Due to the slightly success of protein secondary structure prediction using the
      various algorithmic and non-algorithmic techniques, similar techniques have been
      developed for predicting gamma-turns in proteins by Kaur and Raghava [2003. A
      neural-network based method for prediction of gamma-turns in proteins from
      multiple sequence alignment. Protein Sci. 12, 923-929]. However, the major
      limitation of previous methods was inability in predicting gamma-turn types. In a
      recent investigation we introduced a sequence based predictor model for
      predicting gamma-turn types in proteins [Jahandideh, S., Sabet Sarvestani, A.,
      Abdolmaleki, P., Jahandideh, M., Barfeie, M, 2007a. gamma-turn types prediction
      in proteins using the support vector machines. J. Theor. Biol. 249, 785-790]. In
      the present work, in order to analyze the effect of sequence and structure in the
      formation of gamma-turn types and predicting gamma-turn types in proteins, we
      applied novel hybrid neural discriminant modeling procedure. As the result, this
      study clarified the efficiency of using the statistical model preprocessors in
      determining the effective parameters. Moreover, the optimal structure of neural
      network can be simplified by a preprocessor in the first stage of hybrid
      approach, thereby reducing the needed time for neural network training procedure
      in the second stage and the probability of overfitting occurrence decreased and a
      high precision and reliability obtained in this way.

PMID- 19409397
TI  - Tissue viability imaging: microvascular response to vasoactive drugs induced by
      iontophoresis.
AB  - When one is studying the physiology of the cutaneous microcirculation there is a
      need for relevant non-invasive and versatile techniques. In this study we used a
      new optical device, the tissue viability imager (TiVi), to map changes in
      cutaneous microvascular concentrations of red blood cells during iontophoresis of
      vasoactive substances (noradrenaline (NA) and phenylephrine (Phe) for
      vasoconstriction and acetylcholine (ACh) and sodium nitroprusside (SNP) for
      vasodilatation). We aimed to present data both individually and pooled, using a
      four-variable logistic dose response model that is commonly used in similar in
      vitro vascular studies. The accuracy of the TiVi was also investigated by
      calculating the coefficient of variation and comparing it with similar tests
      previously done using laser Doppler imaging. Tests were also performed using the
      TiVi and LDPI simultaneously to further compare the two methods. Results showed
      that the TiVi is capable of quantifying vascular responses to iontophorised
      noradrenaline and phenylephrine without the need to increase background flow
      first. Fitting the TiVi data to the dose response model resulted in ED(50)-values
      with narrow confidence intervals and acceptable r(2) values. Mean ED(50)-values
      for the TiVi did not differ significantly from similar values obtained using
      laser Doppler. Results further seem to suggest that when the blood perfusion
      increases during vasodilatation in skin the initial phase relies mainly on an
      increase in red blood cell concentration whereas the further perfusion increase
      is due to an increase in red blood cell velocity.

PMID- 19409398
TI  - Preserved endothelial-dependent and endothelial-independent skin vasodilator
      responses in relatives of type 1 diabetes patients.
AB  - Since increased plasma and cell levels of oxidative products have been found in
      non diabetic relatives of type 1 diabetic patients, we hypothesized the
      occurrence of an endothelial dysfunction in these subjects. To verify this
      hypothesis we investigated the skin blood flow responses to iontophoresis of both
      the endothelial-dependent vasodilator acetylcholine (ACh) and the endothelial
      independent vasodilator sodium nitroprusside (SNP) in 31 non diabetic healthy
      relatives (DR) (14 siblings, 17 parents) of 17 type 1 diabetic patients. Twenty
      healthy control subjects (CS) without a family history of diabetes, matched for
      age (+/-5 years) and gender, were also investigated. DR and CS did not
      significantly differ either in basal skin blood flux (6.75+/-0.72 PU and 5.78+/
      0.37 PU, respectively) or in skin vasodilator response to both ACh (728+/-53% and
      711+/-44%, respectively) and SNP iontophoresis (758+/-71% and 731+/-64%,
      respectively). This finding is consistent with a preserved skin microvascular
      endothelial function in the studied subjects. However, since previous data
      suggest that both nitric oxide (NO) and prostacyclin released form the cutaneous
      vascular endothelium have an interchanging compensatory role in controlling the
      skin vasodilator response to ACh iontophoresis, our finding does not allow a
      defect in NO dependent skin vasodilatation to be excluded in the studied
      relatives of diabetic patients.

PMID- 19409399
TI  - The impact of air pollution on the levels of micronuclei measured by automated
      image analysis.
AB  - The measurement of micronuclei (MN) in human peripheral blood lymphocytes is
      frequently used in molecular epidemiology as one of the preferred methods for
      assessing chromosomal damage resulting from environmental mutagen exposure. In
      the present study, we evaluated the effect of exposure to carcinogenic polycyclic
      aromatic hydrocarbons (c-PAHs), volatile organic compounds (VOC) and smoking on
      the frequency of MN in a group of 56 city policemen living and working in Prague.
      The average age of the participants was 34+/-6 years. The study was conducted on
      the same subjects in February and May 2007. The concentrations of air pollutants
      were obtained from personal and stationary monitoring. A statistically
      significant decrease in the levels of pollutants was observed in May when
      compared with February, with the exception of toluene levels measured by
      stationary monitoring. The frequency of MN was determined by the automatic image
      scoring (MetaSystems Metafer 4, version 3.2.1) of DAPI-stained slides. The
      results of the image analysis indicated a significant difference in the frequency
      of MN (mean levels 7.32+/-3.42 and 4.67+/-2.92, for February and May,
      respectively). Our study suggests that automatic image analysis of MN is a highly
      sensitive method for evaluating the effect of c-PAHs and confirms that there are
      no differences between smokers and nonsmokers. These results demonstrate the
      ability of c-PAHs to increase MN frequency, even if the exposure to c-PAHs
      occurred up to 60 days before the collection of biological material. Our work is
      the first human biomonitoring study focused on the measurement of MN by automated
      image analysis for assessing chromosomal damage as a result of environmental
      mutagen exposure.

PMID- 19409400
TI  - Jingzhaotoxin-IX, a novel gating modifier of both sodium and potassium channels
      from Chinese tarantula Chilobrachys jingzhao.
AB  - Tarantula Chilobrachys jingzhao is one of the most venomous species distributed
      in China. In this study, we have isolated and characterized a novel neurotoxin
      named Jingzhaotoxin-IX (JZTX-IX) from the venom of the tarantula. JZTX-IX is a C
      terminally amidated peptide composed of 35 amino acid residues. The toxin shows
      74% sequence identity with CcoTx3 from southeastern Africa tarantula Ceratogyrus
      cornuatus. JZTX-IX was found to interact with multiple types of ion channels
      including voltage-gated sodium channels (both tetrodotoxin-resistant and
      tetrodotoxin-sensitive isoforms) and Kv2.1 channel. The toxin had no effect on
      delayed rectifier potassium channel Kv1.1, 1.2 and 1.3. JZTX-IX shifted the
      voltage dependence of channel activation to more positive voltages, but binding
      of toxin to ion channels was not reversible by extreme depolarization. In
      addition, JZTX-IX could bias the activities of ion channels towards closed state
      because the time constant for decay (channel deactivation) of tail currents
      became faster in the presence of toxin. Taken together with the finding that 10
      microM JZTX-IX completely blocked ion channels at resting potential without
      pulsing, we propose that JZTX-IX is a gating modifier showing low selectivity for
      ion channel types and trapping voltage sensor at closed state.

PMID- 19409401
TI  - Impairment of episodic and semantic autobiographical memory in patients with mild
      cognitive impairment and early Alzheimer's disease.
AB  - Autobiographical memory includes the retrieval of personal semantic data and the
      remembrance of incident or episodic memories. In retrograde amnesias, it has been
      observed that recall of autobiographical memories of recent events is poorer than
      recall of remote memories. Alzheimer's disease (AD) may also be associated with a
      temporal gradient (TG) in memory decline, though studies have yielded
      inconsistent results on this point. They have also yielded inconsistent results
      on whether AD might differentially affect semantic and episodic remembrance.
      Here, we compared autobiographical memory of childhood, early adulthood, and
      recent life among healthy control (HC) subjects, patients with early AD, and
      patients with amnesic mild cognitive impairment (aMCI). Both the aMCI and AD
      patients exhibited declines in recall of autobiographical incidents and semantic
      information. In AD patients, both components of autobiographical memory had a
      clear TG, with better preservation of memories of childhood than those of early
      adulthood and recent life. The TG of autobiographical memory decline in AD
      patients is more compatible with the Cortical Reallocation Theory than with the
      Multiple Trace Theory of memory consolidation. In contrast to AD patients, aMCI
      patients exhibited impaired recall of personal facts and autobiographical
      incidents relating only to recent life. The significant decline in
      autobiographical memory for recent life that occurred in aMCI patients suggests
      that deterioration of consolidation of personal facts and events begins with
      commencement of functional impairment in the hippocampus.

PMID- 19409402
TI  - Criteria to distinguish between natural situations and illegal use of boldenone,
      boldenone esters and boldione in cattle 2. Direct measurement of 17beta-boldenone
      sulpho-conjugate in calf urine by liquid chromatography--high resolution and
      tandem mass spectrometry.
AB  - Boldenone is banned in the European Union (Directive 96/22/EC) as growth promoter
      for meat producing animals. Boldione (ADD), boldenone and boldenone esters
      (mainly the undecylenate form) are commercially available as anabolic
      preparations, either to the destination of human, horse or cattle. Since the late
      90s, the natural occurrence of boldenone metabolites has been reported in cattle.
      According to EU regulation, the unambiguous demonstration of boldenone
      administration in bovine urine should be provided on the basis of boldenone
      identification in the corresponding conjugate fraction. An analytical method has
      been developed and validated according to current standards with main concern to
      the measurement of intact 17beta-boldenone-sulphate. The analytical procedure
      included direct extraction-purification of target analyte on octadecylsilyl
      cartridges and direct detection of phase II metabolite by liquid chromatography
      (negative electrospray), tandem mass spectrometry (QqQ) or high resolution mass
      spectrometry (Orbitrap). Decision limit (CCalpha) and detection capability
      (CCbeta) were respectively 0.2 microg L(-1) and 0.4 microg L(-1) on triple
      quadrupole and 0.1 microg L(-1) and 0.2 microg L(-1) on hybrid system. The method
      was successfully applied to the analysis of incurred samples collected in
      different experiments. 17beta-Boldenone-sulphate was measurable up to 36h after
      oral administration of boldione, and 30 days after 17beta-boldenone undecylenate
      intra-muscular injection. This conjugate form was never detected in non-treated
      animals, confirming its status of definitive candidate marker for boldenone
      administration in calf.

PMID- 19409403
TI  - Protective effect of bile acid derivatives in phalloidin-induced rat liver
      toxicity.
AB  - Phalloidin causes severe liver damage characterized by marked cholestasis, which
      is due in part to irreversible polymerization of actin filaments. Liver uptake of
      this toxin through the transporter OATP1B1 is inhibited by the bile acid
      derivative BALU-1, which does not inhibit the sodium-dependent bile acid
      transporter NTCP. The aim of the present study was to investigate whether BALU-1
      prevents liver uptake of phalloidin without impairing endogenous bile acid
      handling and hence may have protective effects against the hepatotoxicity induced
      by this toxin. In anaesthetized rats, i.v. administration of BALU-1 increased
      bile flow more than taurocholic acid (TCA). Phalloidin administration decreased
      basal (-60%) and TCA-stimulated bile flow (-55%) without impairing bile acid
      output. Phalloidin-induced cholestasis was accompanied by liver necrosis,
      nephrotoxicity and haematuria. In BALU-1-treated animals, phalloidin-induced
      cholestasis was partially prevented. Moreover haematuria was not observed, which
      was consistent with histological evidences of BALU-1-prevented injury of liver
      and kidney tissue. HPLC-MS/MS analysis revealed that BALU-1 was secreted in bile
      mainly in non-conjugated form, although a small proportion (<5%) of tauro-BALU-1
      was detected. BALU-1 did not inhibit the biliary secretion of endogenous bile
      acids. When highly choleretic bile acids, - ursodeoxycholic (UDCA) and
      dehydrocholic acid (DHCA) - were administered, they were found less efficient
      than BALU-1 in preventing phalloidin-induced cholestasis. Biliary phalloidin
      elimination was low but it was increased by BALU-1>TCA>DHCA>UDCA. In conclusion,
      BALU-1 is able to protect against phalloidin-induced hepatotoxicity, probably due
      to an inhibition of the liver uptake and an enhanced biliary secretion of this
      toxin.

PMID- 19409404
TI  - Toxicogenomic effects common to triazole antifungals and conserved between rats
      and humans.
AB  - The triazole antifungals myclobutanil, propiconazole and triadimefon cause
      varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in
      rodent in vivo models. To identify biological pathways consistently modulated
      across multiple timepoints and various study designs, gene expression profiling
      was conducted on rat livers from three separate studies with triazole treatment
      groups ranging from 6 h after a single oral gavage exposure, to prenatal to adult
      exposures via feed. To explore conservation of responses across species, gene
      expression from the rat liver studies were compared to in vitro data from rat and
      human primary hepatocytes exposed to the triazoles. Toxicogenomic data on
      triazoles from 33 different treatment groups and 135 samples (microarrays)
      identified thousands of probe sets and dozens of pathways differentially
      expressed across time, dose, and species--many of these were common to all three
      triazoles, or conserved between rodents and humans. Common and conserved pathways
      included androgen and estrogen metabolism, xenobiotic metabolism signaling
      through CAR and PXR, and CYP mediated metabolism. Differentially expressed genes
      included the Phase I xenobiotic, fatty acid, sterol and steroid metabolism genes
      Cyp2b2 and CYP2B6, Cyp3a1 and CYP3A4, and Cyp4a22 and CYP4A11; Phase II
      conjugation enzyme genes Ugt1a1 and UGT1A1; and Phase III ABC transporter genes
      Abcb1 and ABCB1. Gene expression changes caused by all three triazoles in liver
      and hepatocytes were concentrated in biological pathways regulating lipid, sterol
      and steroid homeostasis, identifying a potential common mode of action conserved
      between rodents and humans. Modulation of hepatic sterol and steroid metabolism
      is a plausible mode of action for changes in serum testosterone and adverse
      reproductive outcomes observed in rat studies, and may be relevant to human risk
      assessment.

PMID- 19409405
TI  - Current status of cadmium as an environmental health problem.
AB  - Cadmium is a toxic metal occurring in the environment naturally and as a
      pollutant emanating from industrial and agricultural sources. Food is the main
      source of cadmium intake in the non-smoking population. The bioavailability,
      retention and toxicity are affected by several factors including nutritional
      status such as low iron status. Cadmium is efficiently retained in the kidney
      (half-time 10-30 years) and the concentration is proportional to that in urine (U
      Cd). Cadmium is nephrotoxic, initially causing kidney tubular damage. Cadmium can
      also cause bone damage, either via a direct effect on bone tissue or indirectly
      as a result of renal dysfunction. After prolonged and/or high exposure the
      tubular injury may progress to glomerular damage with decreased glomerular
      filtration rate, and eventually to renal failure. Furthermore, recent data also
      suggest increased cancer risks and increased mortality in environmentally exposed
      populations. Dose-response assessment using a variety of early markers of kidney
      damage has identified U-Cd points of departure for early kidney effects between
      0.5 and 3 microg Cd/g creatinine, similar to the points of departure for effects
      on bone. It can be anticipated that a considerable proportion of the non-smoking
      adult population has urinary cadmium concentrations of 0.5 microg/g creatinine or
      higher in non-exposed areas. For smokers this proportion is considerably higher.
      This implies no margin of safety between the point of departure and the exposure
      levels in the general population. Therefore, measures should be put in place to
      reduce exposure to a minimum, and the tolerably daily intake should be set in
      accordance with recent findings.

PMID- 19409406
TI  - Pharmacokinetic analysis of trichloroethylene metabolism in male B6C3F1 mice:
      Formation and disposition of trichloroacetic acid, dichloroacetic acid, S-(1,2
      dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine.
AB  - Trichloroethylene (TCE) is a well-known carcinogen in rodents and concerns exist
      regarding its potential carcinogenicity in humans. Oxidative metabolites of TCE,
      such as dichloroacetic acid (DCA) and trichloroacetic acid (TCA), are thought to
      be hepatotoxic and carcinogenic in mice. The reactive products of glutathione
      conjugation, such as S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and S-(1,2
      dichlorovinyl) glutathione (DCVG), are associated with renal toxicity in rats.
      Recently, we developed a new analytical method for simultaneous assessment of
      these TCE metabolites in small-volume biological samples. Since important gaps
      remain in our understanding of the pharmacokinetics of TCE and its metabolites,
      we studied a time-course of DCA, TCA, DCVG and DCVG formation and elimination
      after a single oral dose of 2100 mg/kg TCE in male B6C3F1 mice. Based on systemic
      concentration-time data, we constructed multi-compartment models to explore the
      kinetic properties of the formation and disposition of TCE metabolites, as well
      as the source of DCA formation. We conclude that TCE-oxide is the most likely
      source of DCA. According to the best-fit model, bioavailability of oral TCE was
      approximately 74%, and the half-life and clearance of each metabolite in the
      mouse were as follows: DCA: 0.6 h, 0.081 ml/h; TCA: 12 h, 3.80 ml/h; DCVG: 1.4 h,
      16.8 ml/h; DCVC: 1.2 h, 176 ml/h. In B6C3F1 mice, oxidative metabolites are
      formed in much greater quantities (approximately 3600 fold difference) than
      glutathione-conjugative metabolites. In addition, DCA is produced to a very
      limited extent relative to TCA, while most of DCVG is converted into DCVC. These
      pharmacokinetic studies provide insight into the kinetic properties of four key
      biomarkers of TCE toxicity in the mouse, representing novel information that can
      be used in risk assessment.

PMID- 19409407
TI  - Cytokeratin 8/18 overexpression and complex formation as an indicator of GST-P
      positive foci transformation into hepatocellular carcinomas.
AB  - Screening of the proteome of microdissected glutathione S-transferase placental
      form (GST-P) positive foci and normal-appearing liver on anionic (Q10), and
      cationic (CM10) surface-enhanced laser desorption/ionization time-of-flight mass
      spectrometry (SELDI-TOF-MS) ProteinChip arrays demonstrated significant
      overexpression of cytokeratin 8 (CK8; m/z 54,020), cytokeratin 18 (CK18; m/z
      47,760), microsomal cytochrome 5A (m/z 15,224) and histone type 2 H2aa3 (m/z
      15,964) in the livers of rats initiated with diethylnitrosamine (DEN) followed by
      10 weeks on phenobarbital (PB) at a dose of 500 ppm. Furthermore, formation of
      CK8 and CK18 complexes due to CK8 phosphorylation at Ser73 and Ser431 was found
      to be strongly associated with promotion of hepatocarcinogenesis by PB and the
      development of hepatocellular carcinomas. The data were confirmed by
      immunohistochemistry and real-time Q-PCR and profound overexpression of CK8 and
      CK18 (CK8/18) proteins and mRNAs were detected in several large size GST-P
      positive foci and liver tumors. A strong correlation between CK8/18 positive foci
      development and multiplicity of hepatocellular carcinomas was further observed.
      Moreover, elevation of CK8/18 was strongly associated with induction of cell
      proliferation in GST-P positive foci and tumors. In conclusion, our data imply
      that CK8/18 overexpression, those two cytokeratins complex formation associated
      with histone type 2 H2aa3 up-regulation and intermediate filament reorganization
      may drive neoplastic transformation of GST-P positive foci during rat
      hepatocarcinogenesis leading to the formation of hepatocellular carcinomas.

PMID- 19409409
TI  - Expected values for steps/day in special populations.
AB  - OBJECTIVE: To assemble expected values for free-living steps/day in special
      populations living with chronic illnesses and disabilities. METHOD: Studies
      identified since 2000 were categorized into similar illnesses and disabilities,
      capturing the original reference, sample descriptions, descriptions of
      instruments used (i.e., pedometers, piezoelectric pedometers, accelerometers),
      number of days worn, and mean and standard deviation of steps/day. RESULTS: Sixty
      unique studies represented: 1) heart and vascular diseases, 2) chronic
      obstructive lung disease, 3) diabetes and dialysis, 4) breast cancer, 5)
      neuromuscular diseases, 6) arthritis, joint replacement, and fibromyalgia, 7)
      disability (including mental retardation/intellectual difficulties), and 8) other
      special populations. A median steps/day was calculated for each category. Waist
      mounted and ankle-mounted instruments were considered separately due to
      fundamental differences in assessment properties. For waist-mounted instruments,
      the lowest median values for steps/day are found in disabled older adults (1214
      steps/day) followed by people living with COPD (2237 steps/day). The highest
      values were seen in individuals with Type 1 diabetes (8008 steps/day), mental
      retardation/intellectual disability (7787 steps/day), and HIV (7545 steps/day).
      CONCLUSION: This review will be useful to researchers/practitioners who work with
      individuals living with chronic illness and disability and require such
      information for surveillance, screening, intervention, and program evaluation
      purposes.

PMID- 19409410
TI  - Highly sulphated galactan from Halymenia durvillei (Halymeniales, Rhodophyta), a
      red seaweed of Madagascar marine coasts.
AB  - Halymenia durvillei is a red seaweed with a great potential as sulphated galactan
      producer collected in the coastal waters of small island of Madagascar (Nosy-be
      in Indian Ocean). To elucidate the structure of its polysaccharide, NMR (1H and
      13C), FTIR, HPAEC and different colorimetric methods were carried out. It has
      been shown that this polysaccharide, consisted mainly of galactose, was branched
      by xylose and galactose in minor amounts. Arabinose and fucose were also
      detected. This galactan was found highly sulphated (42%, w/w) and pyruvylated
      (1.8%, w/w). Analysis of glycosidic linkages by CPG-MS and 13C NMR indicated that
      the polysaccharide has the defining linear backbone of alternating 3-beta-D
      galactopyranosyl units and 4-linked alpha-L/D-galactopyranosyl residues. 3,6
      Anhydrogalactose units have been also detected in minor quantity. This lambda
      carrageenan like polysaccharide has shown original sulphatation patterns with 2-O
      (26%) or 2/6-O (58%) sulphated 3-linked beta-D-galactopyranosyl units and 6-O
      (19%) or 2/6-O (47%) 4-linked alpha-L/D-galactopyranosyl residues.

PMID- 19409411
TI  - Antioxidative activity of polysaccharide fractions isolated from Lycium barbarum
      Linnaeus.
AB  - Antioxidant activity of polysaccharide fractions isolated from Lycium barbarum
      Linnaeus was evaluated. Polysaccharides were extracted with boiling water,
      followed by precipitating with ethanol, protein hydrolysis, dialysis, and
      fractionation with a DEAE-Sepharose CL-6B column. A total of 4 fractions,
      including 1 neutral polysaccharide (LBPN) and 3 acidic polysaccharides were
      obtained, and compared with crude polysaccharide (CP), crude extract of
      polysaccharide (CE), deproteinated polysaccharide (DP), and deproteinated and
      dialyzed polysaccharide (DDP) for antioxidative activity. With the exception of
      CE and DDP, most polysaccharides were effective in scavenging DPPH and ABTS(.)+
      free radicals, superoxide anion and hydroxyl radical at 1000 microg/mL.

PMID- 19409412
TI  - Stabilization effects of kosmotrope systems on ornithine carbamoyltransferase.
AB  - In the present article the influence of salts and additives, such as trehalose,
      NaCl, ornithine, sodium phosphate and ammonium sulphate, on ornithine
      carbamoyltransferase (OCTase) is investigated in order to study the OCTase
      stabilization process as a function of solutes and to point out the fundamental
      role played by an enhancement of hydrophobic interactions. The synergic use of
      different techniques, such as neutron spectroscopy, UV-vis spectroscopy, activity
      and thermal measurements, allows to highlight the cosolute capability to avoid
      thermal inactivation, to induce important changes in secondary and tertiary
      enzyme structure and to stabilize biological macromolecules.

PMID- 19409413
TI  - Molecular interaction of human serum albumin with paracetamol: spectroscopic and
      molecular modeling studies.
AB  - The interaction between paracetamol and human serum albumin (HSA) under
      physiological conditions has been investigated by fluorescence, circular
      dichroism (CD) and docking. Fluorescence data revealed that the fluorescence
      quenching of HSA by paracetamol was the result of the formed complex of HSA
      paracetamol, and the binding constant (K(a)) and binding number obtained is 1.3 x
      10(4) at 298 K and 2, respectively for the primary binding site. Circular
      dichorism spectra showed the induced conformational changes in HSA by the binding
      of paracetamol. Moreover, protein-ligand docking study indicated that
      paracetamols (two paracetamols bind to HSA) bind to residues located in the
      subdomain IIIA.

PMID- 19409408
TI  - Overexpression of methionine-R-sulfoxide reductases has no influence on fruit fly
      aging.
AB  - Methionine sulfoxide reductases (Msrs) are enzymes that repair oxidized
      methionine residues in proteins. This function implicated Msrs in antioxidant
      defense and the regulation of aging. There are two known Msr types in animals:
      MsrA specific for the reduction of methionine-S-sulfoxide, and MsrB that
      catalyzes the reduction of methionine-R-sulfoxide. In a previous study,
      overexpression of MsrA in the nervous system of Drosophila was found to extend
      lifespan by 70%. Overexpression of MsrA in yeast also extended lifespan, whereas
      MsrB overexpression did so only under calorie restriction conditions. The effect
      of MsrB overexpression on lifespan has not yet been characterized in animal model
      systems. Here, the GAL4-UAS binary system was used to drive overexpression of
      cytosolic Drosophila MsrB and mitochondrial mouse MsrB2 in whole body, fatbody,
      and the nervous system of flies. In contrast to MsrA, MsrB overexpression had no
      consistent effect on the lifespan of fruit flies on either corn meal or sugar
      yeast diets. Physical activity, fecundity, and stress resistance were also
      similar in MsrB-overexpressing and control flies. Thus, MsrA and MsrB, the two
      proteins with similar function in antioxidant protein repair, have different
      effects on aging in fruit flies.

PMID- 19409414
TI  - Promotion proliferation effect of a polysaccharide from Aloe barbadensis Miller
      on human fibroblasts in vitro.
AB  - A polysaccharide fraction was isolated from fresh Aloe barbadensis Miller leaves,
      which can promote the wound healing of the superficial II scald model mice. The
      monosaccharide composition and linkage determination were investigated by
      methylation and GC-MS, acetylation and GC, 13C NMR and DEPT. The results show
      that its glycosyl components contain D-glucose, D-galactose, D-xylose in a molar
      ratio of 5:5:1, and the API consists of a backbone of -->2)-alpha-D-Galp-(1-->2)
      alpha-D-Glcp-(1-->, having a branch of alpha-D-xylofuranosyl residue that is (1-
      >3) linkage at O-3 of alpha-D-galactopyranosyl residue. It was found that the API
      could enhance proliferation of the human fibroblasts in vitro. The mechanisms of
      promotion proliferation were studied preliminarily.

PMID- 19409415
TI  - Bioactive and metal uptake studies of carboxymethyl chitosan-graft-D-glucuronic
      acid membranes for tissue engineering and environmental applications.
AB  - Carboxymethyl chitosan-graft-D-glucuronic acid (CMCS-g-D-GA) was prepared by
      grafting D-GA onto CMCS in the presence of 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC) and then the membranes were made from it.
      In this work, the bioactivity studies of CMCS-g-D-GA membranes were carried out
      and then characterized by SEM, CLSM, XRD and FT-IR. The CMCS-g-D-GA membranes
      were found to be bioactive. The adsorption of Ni2+, Zn2+ and Cu2+ ions onto CMCS
      g-D-GA membranes has also been investigated. The maximum adsorption capacity of
      CMCS-g-D-GA for Ni2+, Zn2+ and Cu2+ was found to be 57, 56.4 and 70.2 mg/g,
      respectively. Hence, these membranes were useful for tissue engineering,
      environmental and water purification applications.

PMID- 19409418
TI  - WITHDRAWN: Evaluation of two automated systems for analyzing partner preference
      tests.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 19409417
TI  - Behavioural and histological observations of sensory impairment caused by tight
      ligation of the trigeminal nerve in mice.
AB  - Dental treatments sometimes cause sensory impairment, especially in the region
      innervated by the third division of the trigeminal nerve. The most frequent
      symptoms are loss of sensation and abnormal sensation. Although most studies have
      addressed the neuropathic symptom "allodynia" using experimental animal models of
      the infraorbital nerve, there is little information regarding the sensory
      impairment that frequently occurs clinically. Therefore, different experimental
      models are required to clarify the mechanisms of the clinical effects, and
      previous experimental models have been limited to rats. Here, we report a sensory
      impairment model in mice whose mechanical touch threshold increased after tight
      ligation of the mental nerve. Habituation before surgery by mechanical touching
      of the face enabled us to observe the long-term chronological changes in
      sensation. The mechanical touch thresholds within the mental nerve region were
      measured for 70 postoperative (PO) days. Changes in the distribution of substance
      P (SP) were evaluated by immunohistochemistry to clarify the involvement of
      axonal flow in the sensory impairment and its recovery. The mechanical touch
      thresholds transiently increased by PO days 2-3, but decreased to the
      preoperative levels at around PO day 14. Apparent SP immunoreactivity was
      recognizable on the medial side to the ligation at PO days 2-3 and disappeared at
      PO day 7. These behavioural and immunohistochemical changes appeared to exhibit
      similar time courses, suggesting a possible relationship between them. Therefore,
      we suggest that our experimental mouse model could represent a new model for
      clarifying the mechanism of the sensory impairment caused by peripheral nerve
      injury.

PMID- 19409419
TI  - Sensitive and rapid detection of peach latent mosaic viroid by the reverse
      transcription loop-mediated isothermal amplification.
AB  - A reverse transcription loop-mediated isothermal amplification (RT-LAMP) method
      for the detection of peach latent mosaic viroid (PLMVd) was developed. Four
      primer sets (OLD, OLD1, NEW, and Fukuta's) were designed originally. Based on
      initial experiments the set OLD1 was selected for further evaluation. Simple and
      accelerated RT-LAMP was preformed using degenerate and no degenerate forward-loop
      (F-loop) and backward-loop (B-Loop) primers. Degenerate primers were selected,
      and after determination of their best concentration (0.8microM), the reaction was
      preformed at different temperatures (60-67.5 degrees C) using three different
      betaine concentrations (0.8M, 0.4M, and 0.2M). Optimal conditions were found to
      be 62.5 degrees C and 0.8M betaine. Under these conditions, using tRNA as
      template, PLMVd was detected within only 32min, compared to 180min of RT-PCR,
      using the Real Time Turbimeter (LA200, Teramecs) which measures the turbidity
      caused by the production of insoluble magnesium pyrophosphate. In addition, RT
      LAMP was more sensitive than RT-PCR. PLMVd was detected in peach, plum, apricot,
      pear, wild pear and quince samples.

PMID- 19409416
TI  - Methylmercury disruption of embryonic neural development in Drosophila.
AB  - Methylmercury (MeHg) is a potent environmental neurotoxin that preferentially
      targets the developing embryonic nervous system. While a number of cytotoxic
      mechanisms of MeHg have been characterized in differentiated cells its mode of
      action in the developing nervous system in vivo is less clear. Studies in primate
      and rodent models demonstrate aberrant cell migration and disorganized patterning
      of cortical layers in the brain following MeHg exposure. However, defining the
      molecular and cellular pathways targeted by MeHg will require more genetically
      accessible animal models. In this study, we instigate a method of in vitro MeHg
      exposure using Drosophila embryos. We demonstrate dose-dependent inhibition of
      embryonic development with MeHg revealed by a failure of embryos to hatch to the
      larval stage. In addition, we document definitive phenotypes in neural
      development showing abnormalities in neuronal and glial cell patterning
      consistent with disrupted migration. We observe pronounced defects in neurite
      outgrowth in both central and peripheral neurons. Ectopic expression of the Nrf2
      transcription factor in embryos, a core factor in the antioxidant response
      element (ARE) pathway, enhances embryonic development and hatching in the
      presence of MeHg, illustrating the power of this model for investigation of
      candidate MeHg tolerance genes. Our data establish a utility for the Drosophila
      embryo model as a platform for elucidating MeHg sensitive pathways in neural
      development.

PMID- 19409420
TI  - Towards construction of viral vectors based on avian coronavirus infectious
      bronchitis virus for gene delivery and vaccine development.
AB  - Manipulation of the coronavirus genome to accommodate and express foreign genes
      is an attractive approach for gene delivery and vaccine development. By using an
      infectious cloning system developed recently for the avian coronavirus infectious
      bronchitis virus (IBV), the enhanced green fluorescent protein (EGFP) gene, the
      firefly luciferase gene and several host and viral genes (eIF3f, SARS ORF6,
      Dengue virus 1 core protein gene) were inserted into various positions of the IBV
      genome, and the effects on gene expression, virus recovery, and stability in cell
      culture were studied. Selected viruses were also inoculated into chicken embryos
      for studies of foreign gene expression at different tissue level. The results
      demonstrated the stability of recombinant viruses depends on the intrinsic
      properties of the foreign gene itself as well as the position at which the
      foreign genes were inserted. For unstable viruses, the loss of expression of the
      inserted genes was found to result from a large deletion of the inserted gene and
      even IBV backbone sequences. This represents a promising system for development
      of coronavirus-based gene delivery vectors and vaccines against coronavirus and
      other viral infections in chicken.

PMID- 19409421
TI  - Kinetoplastid papain-like cysteine peptidases.
AB  - Cysteine peptidases are important for growth and survival of kinetoplastid
      parasites. The best characterised are those homologous to mammalian cathepsins B
      and L. To address a somewhat confusing terminology, we introduce a unifying
      nomenclature for kinetoplastid CATB and CATL peptidases. We review their
      evolutionary relatedness, genomic organisation, developmental expression,
      subcellular location and physiological functions. In addition, the applications
      of kinetoplastid CATB and CATL enzymes as vaccine candidates, diagnostic markers
      and drug targets are discussed.

PMID- 19409422
TI  - Emerging concepts in the regulation of membrane-type 1 matrix metalloproteinase
      activity.
AB  - Pericellular proteolysis mediated by membrane-type 1 matrix metalloproteinase
      (MT1-MMP) represents an essential component of the cellular machinery involved in
      the dissolution and penetration of ECM barriers by tumor cells. Although most
      studies on the proinvasive properties of MT1-MMP have focused on its unusually
      broad proteolytic activity towards several ECM components and cell surface
      receptors, recent evidence indicate that the cytoplasmic domain of the enzyme
      also actively participates in tumor cell invasion by regulating the cell surface
      localization of MT1-MMP as well as the activation of signal transduction
      cascades. The identification of the molecular events by which the intracellular
      domain of MT1-MMP links proteolysis of the surrounding matrix by the enzyme to
      modification of cell function may thus provide important new information on the
      mechanisms by which this enzyme controls the invasive behavior of neoplastic
      cells in vivo.

PMID- 19409423
TI  - Multiplex real-time PCR for detection, identification and quantification of
      'Candidatus Liberibacter solanacearum' in potato plants with zebra chip.
AB  - The new Liberibacter species, 'Candidatus Liberibacter solanacearum' (Lso)
      recently associated with potato/tomato psyllid-transmitted diseases in tomato and
      capsicum in New Zealand, was found to be consistently associated with a newly
      emerging potato zebra chip (ZC) disease in Texas and other southwestern states in
      the USA. A species-specific primer LsoF was developed for both quantitative real
      time PCR (qPCR) and conventional PCR (cPCR) to detect and quantify Lso in
      infected samples. In multiplex qPCR, a plant cytochrome oxidase (COX)-based probe
      primer set was used as a positive internal control for host plants, which could
      be used to reliably access the DNA extraction quality and to normalize qPCR data
      for accurate quantification of the bacterial populations in environment samples.
      Neither the qPCR nor the cPCR using the primer and/or probe sets with LsoF
      reacted with other Liberibacter species infecting citrus or other potato
      pathogens. The low detection limit of the multiplex qPCR was about 20 copies of
      the target 16S rDNA templates per reaction for field samples. Lso was readily
      detected and quantified in various tissues of ZC-affected potato plants collected
      from fields in Texas. A thorough but uneven colonization of Lso was revealed in
      various tissues of potato plants. The highest Lso populations were about 3x10(8)
      genomes/g tissue in the root, which were 3-order higher than those in the above
      ground tissues of potato plants. The Lso bacterial populations were normally
      distributed across the ZC-affected potato plants collected from fields in Texas,
      with 60% of ZC-affected potato plants harboring an average Lso population from
      10(5) to 10(6) genomes/g tissue, 4% of plants hosting above 10(7) Lso genomes/g
      tissue, and 8% of plants holding below 10(3) Lso genomes/g tissue. The rapid,
      sensitive, specific and reliable multiplex qPCR showed its potential to become a
      powerful tool for early detection and quantification of the new Liberibacter
      species associated with potato ZC, and will be very useful for the potato
      quarantine programs and seed potato certification programs to ensure the
      availability of clean seed potato stocks and also for epidemiological studies on
      the disease.

PMID- 19409424
TI  - N2pc and attentional capture by colour and orientation-singletons in pure and
      mixed visual search tasks.
AB  - The capture of attention by singleton stimuli in visual search is a matter of
      contention. Some authors propose that singletons capture attention in a bottom-up
      fashion if they are salient. Others propose that capture is contingent upon
      whether or not the stimuli share task-relevant attributes with the target. This
      study assessed N2pc elicited by colour and orientation singletons in a mixed task
      (the singleton defined as target changed block-to-block), and a pure task (the
      target was the same across the whole task). Both singletons elicited N2pc when
      acting as targets; when acting as non-targets, orientation singletons elicited
      N2pc only in the mixed task. The results suggest that the singletons were not
      salient enough to engage attention in a purely bottom-up fashion. Elicitation of
      N2pc by non-targets in the mixed task should be attributed to top-down processes
      associated with the current task. Stimuli that act as targets in part of the
      blocks become not completely irrelevant when non-targets.

PMID- 19409425
TI  - Primary sensory neuronal expression of SLURP-1, an endogenous nicotinic
      acetylcholine receptor ligand.
AB  - Secreted mammalian Ly6/urokinase plasminogen activator receptor-related protein-1
      (SLURP-1) is a recently identified, endogenous ligand of the alpha7 subunit of
      nicotinic acetylcholine receptors. SLURP-1 is also the causative gene for an
      autosomal recessive palmoplantar keratoderma, Mal de Meleda. Although the
      function of SLURP-1 in keratinocyte development and differentiation has been
      extensively studied, little is known about its role in the nervous system. In the
      present study, we analyzed SLURP-1 expression in the spinal cord of rats, as a
      number of studies suggest spinal nicotinic acetylcholine receptors are important
      modulators of pain transmission. We detected intense SLURP-1 immunoreactivity in
      the dorsal horn of the spinal cord, especially in lamina I and outer II. In
      dorsal root ganglia, SLURP-1 immunoreactivity was detected in small- to medium
      sized neurons, where in situ hybridization also revealed the presence of SLURP-1
      mRNA. Fluorescent labeling of SLURP-1 partially overlapped that of calcitonin
      gene related peptide (CGRP) or substance P (SP) in both the spinal cord dorsal
      horn and glabrous skin, and electron microscopic analysis revealed colocalization
      of SLURP-1 with SP or CGRP, in large synaptic vesicles in terminals within the
      superficial layer of the spinal cord. Finally, sciatic nerve axotomy reduced
      levels of SLURP-1 immunoreactivity in parallel with that of SP and CGRP in the
      ipsilateral superficial dorsal horn. These findings suggest that SLURP-1 is
      expressed in a subset of primary peptidergic sensory neurons.

PMID- 19409426
TI  - Three-dimensional distribution of Fos-positive neurons in the supramammillary
      nucleus of the rat exposed to novel environment.
AB  - The supramammillary nucleus (SuM) in the hypothalamus is proposed to regulate the
      function of the hippocampus through distinct fiber connection. Several
      investigations suggest that the SuM is relevant to anxiety and defensive
      behavior. Function of the SuM, however, is not known exactly. In order to
      demonstrate the spatial activation of the SuM in physiologically behaving rats,
      we investigated Fos induction in the SuM by exposure to novel environment. To
      correct uneven background in microscopic preparations, we applied a convolution
      filter, resulting in reliable automatic counting of Fos-positive neurons and
      analyzed the distribution of Fos-positive neurons in the whole region of SuM. A
      large number of Fos-positive neurons were observed throughout the entire SuM
      after rats exposed to a novel open field. A three-dimensional density map
      revealed that density of the Fos-positive neurons was highest in the medial SuM,
      especially in its core regions. Based on these results we suggest that the medial
      SuM modulates defensive behavior and that the lateral SuM modulates emotional and
      memory functions of the hippocampus.

PMID- 19409428
TI  - Self-oscillating gel as novel biomimetic materials.
AB  - Stimuli-responsive polymers and their application to biomaterials have been
      widely studied. On the other hand, as a novel biomimetic polymer, we have been
      studying the polymer with an autonomous self-oscillating function by utilizing
      oscillating chemical reactions. So far, we succeeded in developing a novel self
      oscillating polymer and gels by utilizing the oscillating reaction, called the
      Belousov-Zhabotinsky (BZ) reaction, which is recognized as a chemical model for
      understanding several autonomous phenomena in biological systems. The self
      oscillating polymer is composed of poly(N-isopropylacrylamide) (PNIPAAm) network
      in which the catalyst for the BZ reaction is covalently immobilized. Under the
      coexistence of the reactants, the polymer undergoes spontaneous cyclic soluble
      insoluble changes or swelling-deswelling changes (in the case of gel) without any
      on-off switching of external stimuli. In this paper, our recent studies on the
      self-oscillating polymer gels and the design of functional material systems using
      the polymer are summarized.

PMID- 19409427
TI  - Preparation and characterization of protein loaded microspheres based on a
      hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid).
AB  - The purpose of this study was to investigate the suitability of a novel
      hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid)
      (PLHMGA), as controlled release system for pharmaceutical proteins. Dextran Blue
      (as a macromolecular model compound) and lysozyme-loaded PLHMGA and PLGA (control
      formulation) microspheres were prepared by a solvent evaporation technique. The
      Dextran Blue and lysozyme loaded PLHMGA microspheres prepared with 10% polymer
      solution showed, because of a high porosity, a high burst release (35-75%) and
      the remaining content was released in a sustained manner for 15-20 days. The
      microspheres prepared with 15 and 20% polymer solution had a lower porosity and
      showed a pulsed release after day 8 and in 27 days they released more than 90% of
      Blue Dextran. The release of lysozyme was incomplete, likely due to aggregation
      of part of the encapsulated protein. Spectroscopic analysis of the released
      lysozyme indicated fully preserved secondary/tertiary structure and an enzyme
      activity assay showed that the specific activity of the released protein was
      maintained. An in vitro degradation study showed that the release of Blue Dextran
      and lysozyme is essentially controlled by the degradation of the microspheres.
      This study shows that microspheres made of the hydroxylated aliphatic polyester,
      poly(lactic-co-hydroxymethyl glycolic acid), are promising systems for the
      controlled release of pharmaceutical proteins.

PMID- 19409429
TI  - Cellular uptake, distribution and cytotoxicity of the hydrophobic cell
      penetrating peptide sequence PFVYLI linked to the proapoptotic domain peptide
      PAD.
AB  - The capacity of cell penetrating peptides (CPPs) to breach biological membranes
      offers hope for their utilisation as vectors for the delivery of small molecule
      drugs and macromolecular therapeutics. Using three different cell systems,
      including primary human cells, we have studied the uptake, subcellular
      localisation and effect on cell viability of the well characterised octaarginine
      and the more recently discovered hydrophobic PFVYLI peptide, either alone, or
      conjugated to the proapoptotic domain peptide PAD (klaklak)(2). Octaarginine and
      PFVYLI were efficiently endocytosed into cells at 37 degrees C but an ability to
      translocate directly across the plasma membrane at higher peptide concentrations
      or when uptake experiments were performed on ice was confined to the cationic
      variant. Octaarginine- and PFVYLI-PAD conjugates were cytotoxic, with KG1a
      leukaemia cells being more sensitive than HeLa cells and octaarginine-PAD being
      the most potent conjugate in both cell lines. The effects of the CPP-PAD
      conjugates on cell morphology and permeability was rapid suggesting that
      cytotoxicity is partially mediated at the plasma membrane rather than exclusively
      through induction of apoptosis at the mitochondria. Primary human leukaemia cells
      were more similar to KG1a cells than HeLa cells, suggesting the relative
      sensitivity of leukaemia cells to these peptides could be exploited in vivo.

PMID- 19409430
TI  - Synthesis and characterization of reactive poloxamer 407s for biomedical
      applications.
AB  - The drawbacks of poloxamer hydrogel, such as dissolving quickly in aqueous
      solution, have limited its biomedical application. In order to improve the
      stability of hydrogel, a novel system was developed by combining the reversible
      thermo-sensitive property of poloxamer 407 and the thiol-ene reactivity between
      the acrylate and thiol groups. It was found that the sol-gel transition of the
      acrylate/thiol modified poloxamer 407 mixture could be achieved at body
      temperature even with a low concentration of 17.5 wt.%. Meanwhile, the reaction
      between the acrylate and thiol modified poloxamer 407s occurred spontaneously in
      mimic physiological conditions, thus the hydrogel with crosslinking structure was
      formed. As a result, the stability of the crosslinked hydrogel was enhanced
      remarkably, and the release time of the drug from the crosslinked hydrogel was
      about 4.0 times as long as that from the poloxamer 407 hydrogel. Invitro and
      invivo experiments revealed that the biocompatibilities of the modified poloxamer
      407 hydrogel were similar to that of poloxamer 407. These results indicate that
      the modified poloxamer 407s have potential applications in controlled drug
      release, tissue engineering and cell encapsulation etc.

PMID- 19409431
TI  - Lysine-based peptide-functionalized PLGA foams for controlled DNA delivery.
AB  - Due to its hydrophobicity and negatively charged surfaces, PLGA-based scaffolds
      have encountered problems in controlled-release and tissue engineering
      applications. The effects of charge modification of PLGA micro-porous foams on
      DNA delivery and DNA transfection are investigated herein. Tailor-designed l
      lysine peptides (K4 and K20) were employed to modify the surface charge of PLGA
      foams using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N
      hydroxysuccinimide cross linkers and the effects of charge modification of PLGA
      were examined in three main aspects: DNA adsorption, DNA release properties and
      DNA transfection. Successful conjugation of peptide and DNA adsorption were
      verified by X-ray photoelectron spectroscopy. A plasmid encoding bone
      morphogenetic protein-2 (BMP2) was used throughout the current study and the
      results indicate that adsorption capacity and release behavior of DNA were highly
      dependent on the charge properties of the foam surfaces. The release rates of DNA
      from the K4- and K20-functionalized foams are more sustainable as compared to the
      blank foam. As a result, the sustained release of DNA from modified foams led to
      negligible cytotoxicity and sustained expression of DNA which is favorable for
      DNA delivery and tissue engineering application. Furthermore, the ease of
      fabrication and modification of PLGA foams makes it a promising DNA delivery
      device.

PMID- 19409433
TI  - The HIF-1-active microenvironment: an environmental target for cancer therapy.
AB  - Solid tumors possess unique microenvironments that are exposed to chronic hypoxic
      conditions, so-called tumor hypoxia. Although more than half a century has passed
      since it was suggested that tumor hypoxia correlated with bad treatment outcomes
      and contributed to the recurrence of cancer, no fundamental solution to this
      problem has yet been found. Hypoxia-inducible factor HIF-1 is the main
      transcription factor that regulates the cellular response to hypoxia. It induces
      various genes, whose function is strongly associated with the malignant
      alteration of the entire tumor. The cellular changes induced by HIF-1 are
      extremely important therapeutic targets of cancer therapy, particularly in the
      therapy against refractory cancers. Therefore targeting strategies to overcome
      the HIF-1-active microenvironment are important for cancer therapy.

PMID- 19409434
TI  - Ghrelin modulates fatty acid synthase and related transcription factor mRNA
      levels in a tissue-specific manner in neonatal broiler chicks.
AB  - The endogenous ligand for the growth hormone (GH) secretagogue receptor ghrelin
      is a peptide secreted by the stomach of mammals and stimulates food intake and
      enhances adiposity. In avian species, ghrelin is mainly produced by the
      proventriculus but reduces food intake whereas its effect on lipogenesis in
      different tissues is unknown. We therefore investigated the effects of a single
      intravenous injection of 2.8 microg (1 nmol per chick) recombinant chicken
      ghrelin in neonatal broiler chicks. Besides food intake and plasma corticosterone
      levels, mRNA levels of the key lipogenic enzyme fatty acid synthase (FAS) and its
      related transcription factors sterol regulatory element binding protein-1 (SREBP
      1) and peroxisome proliferator-activated receptor-gamma (PPARgamma) were
      determined in diencephalon, liver and quadriceps femoris muscle before, and 15,
      30, and 60 min after injection. Chicken ghrelin administration induced a
      significant short-term (<30 min) reduction in food intake and markedly elevated
      plasma corticosterone levels. In diencephalon, FAS, SREBP-1 and PPARgamma mRNA
      levels were significantly increased within 15 min after ghrelin injection. These
      observations suggest that central fatty acid metabolism is involved in the
      anorectic effects of ghrelin. In contrast, hepatic mRNA levels of FAS and both
      transcription factors were significantly reduced within 30 min after ghrelin
      injection. In muscle, FAS and transcription factor gene expression was very low
      and not affected by ghrelin. Overall, our results indicate that ghrelin has
      opposite effects on FAS and transcription factor mRNA amounts with increased
      levels in diencephalon (central anorectic effect) and decreased levels in liver
      (peripheral anti-lipogenic effect) in chickens.

PMID- 19409432
TI  - Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble
      anticancer drugs.
AB  - Current clinical and preclinical anticancer formulations are limited by their use
      of toxic excipients and stability issues upon combining different drug
      formulations. We have found that poly(ethylene glycol)-block-poly(d,l lactic
      acid) (PEG-b-PLA) micelles can deliver multiple poorly water-soluble drugs at
      clinically relevant doses. Paclitaxel (PTX), etoposide (ETO), docetaxel (DCTX)
      and 17-allylamino-17-demethyoxygeldanamycin (17-AAG) were solubilized
      individually in PEG-b-PLA micelles. Combinations of PTX/17-AAG, ETO/17-AAG,
      DCTX/17-AAG and PTX/ETO/17-AAG were also solubilized in PEG-b-PLA micelles. PEG-b
      PLA micelles were characterized in terms of drug loading, size, stability and
      drug release. All anticancer agents in all combinations were all solubilized at
      the level of mg/mL and were stable for 24 h in the 2- and 3-drug combination PEG
      b-PLA micelles. The stability of the 2- and 3-drug combination PEG-b-PLA micelles
      was due to the presence of 17-AAG. In vitro, t(1/2) values for 2- and 3-drug
      combination PEG-b-PLA micelles spanned 1-5 h. PEG-b-PLA micelles offer a
      promising alternative for combination drug therapy without formulation related
      side effects.

PMID- 19409435
TI  - Structural and functional diversity of proopiomelanocortin in fish with special
      reference to barfin flounder.
AB  - Proopiomelanocortin (POMC) is a precursor of adrenocorticotropic hormone (ACTH),
      melanocyte-stimulating hormone (MSH), and endorphin (END). We have characterized
      POMC systems in barfin flounder. The results revealed unique aspects of POMC
      systems. Notable features in terms of pituitary functions are the occurrence of
      three functional POMC genes, the mutation of an essential sequence in the beta
      END in one of the genes, occurrence of alpha-MSH in addition to ACTH in the pars
      distalis of the pituitary, and expression of the three genes in a single cell.
      While MSHs stimulate pigment dispersion, expression of the POMC gene and plasma
      levels of MSH do not always respond to background color changes between black and
      white. The functions of MSHs in skin pigmentation are very unique, because
      acetylation at the N-terminal of alpha-MSH inhibits its pigment dispersing
      activity. This is in contrast to results from other teleosts and amphibians, in
      which acetylation increases the activity. In the skin, the POMC gene is expressed
      in the non-chromatophoric dermal cells, indicating that MSH produced in the skin
      de novo has a paracrine function. The detection of MSH peptides in skin extracts
      seems to show that the control of skin pigmentation by MSHs is twofold-endocrine
      control by the pituitary, and paracrine control by the skin itself. Thus, fish
      provide an interesting model to help understand the structural and functional
      diversity of POMC systems. In this review, we provide an overview of our recent
      studies on the characterization of molecules and biological significance of POMC
      systems in barfin flounder.

PMID- 19409436
TI  - Allatostatin-C receptors in mosquitoes.
AB  - In the present work we describe the functional and molecular characterization of
      two Aedes aegypti allatostatin-C receptor paralogs (AeAS-CrA and AeAS-CrB) and
      provide a detailed quantitative study of the expression of the AS-C receptor
      genes in an adult insect. The tissue distribution of the two AS-C receptors
      differed significantly; the mRNA levels of AeAS-CrB in the Malpighian tubules
      were the highest detected, while transcripts for AeAS-CrA were relatively low in
      this tissue. In addition, the transcript levels of both receptors were different
      in the thoracic and abdominal ganglia, corpora allata (CA) and the testis of the
      male. In the CA, the AeAS-CrB mRNA levels were constant from 0 to 72 h after
      female emergence, while the AeAS-CrA levels increased at 72 h. To complement the
      receptor expression studies, we analyzed the tissue specificity for allatostatin
      C mRNA in female mosquitoes. Expression was high in abdominal ganglia and brain.
      Transcript levels of allatostatin-C in the head of females were elevated at
      eclosion and there were no major changes during the first week of adult life or
      after blood feeding. Fluorometric Imaging Plate Reader (FLIPR) recordings of
      calcium transients in HEK293T cells transiently expressing both putative
      receptors showed that they both responded selectively to allatostatin-C
      stimulation in the nanomolar concentration range. However, the peptide showed
      slightly greater affinity for AeAS-CrB than AeAS-CrA. Our studies suggest that
      some of the pleiotropic effects of allatostatin-C in mosquitoes could be mediated
      by the different receptor paralogs. Transcriptional regulation of the AS-C
      receptors may not have a critical role in the changes of CA responsiveness to the
      peptide that we previously described.

PMID- 19409437
TI  - Neuroprotective effects of Astragaloside IV in 6-hydroxydopamine-treated primary
      nigral cell culture.
AB  - Parkinson's disease (PD) is caused by a progressive degeneration of dopaminergic
      neurons in the substantia nigra. Oxidative stress and neural degeneration are
      suggested to be involved in the pathogenesis of Parkinson's disease. In the
      present study, Astragaloside IV (AS-IV) extracted from the dried root of
      Astragalus membranaceus, a well-known Chinese medicine used for the treatment of
      neurodegenerative diseases, was investigated for its capacity to protect
      dopaminergic neurons in experimental Parkinson's disease. By examining the effect
      of AS-IV on 6-hydroxydopamine (6-OHDA)-induced loss of dopaminergic neurons in
      primary nigral culture, we found that AS-IV pretreatment significantly and dose
      dependently attenuated 6-OHDA-induced loss of dopaminergic neurons. Neuronal
      fiber length studies showed that massive neuronal cell death with degenerated
      neurons was observed in those cultures incubated with 6-OHDA, whereas in AS-IV co
      treatments most dopaminergic neurons were seen to be intact and sprouting. In
      flow cytometric analysis, AS-IV resulted in a marked and dose-dependent rescue in
      tyrosine hydrolase (TH)-immunopositive cells from 6-OHDA-induced degeneration of
      dopaminergic neurons. Double immunofluorescence revealed that AS-IV treatment
      alone at concentrations of 100 and 200 microM increased the level of TH and NOS
      (nitrite oxide synthase) immunoreactivities; however, the protective effect of AS
      IV on TH and NOS immunopositive cells in 6-OHDA treated nigral cell cultures was
      only seen at a concentration of 100 microM. These findings show that AS-IV can
      protect dopaminergic neurons against 6-OHDA-induced degeneration. Besides the
      neuroprotective effect, AS-IV alone promoted neurite outgrowth and increased TH
      and NOS immunoreactive of dopaminergic neurons. The neuroprotective and
      neurosprouting effects of AS-IV are specific for dopaminergic neurons and it has
      therapeutic potential in the treatment of PD.

PMID- 19409438
TI  - The XIAP inhibitor Embelin enhances TRAIL-mediated apoptosis in malignant glioma
      cells by down-regulation of the short isoform of FLIP.
AB  - Embelin has been reported to exhibit therapeutic activity in cancer. In this
      study glioblastoma cells and human astrocytes were treated with Embelin, tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of
      both. Treatment with subtoxic doses of Embelin broadly sensitized malignant
      glioma cells to TRAIL-mediated apoptosis. Notably, human astrocytes were not
      significantly affected by the combined treatment consisting of Embelin and TRAIL.
      Combined treatment with Embelin and TRAIL augmented the activation of initiator
      caspases-8/-9 and effector caspases-3/-7, respectively. Furthermore, Embelin down
      regulated the expression of the long- and short-isoform of c-FLIP. In addition,
      forced expression of the short isoform of c-FLIP (S) attenuated apoptosis induced
      by the combination of Embelin and TRAIL. Embelin did not modulate the mRNA levels
      of c-FLIP (S), suggesting that Embelin modulates the expression of c-FLIP in a
      posttranscriptional manner. In summary, the short isoform of c-FLIP is a key
      regulator in TRAIL-Embelin-mediated apoptosis in malignant glioma.

PMID- 19409439
TI  - Melatonin attenuates methamphetamine-induced reduction of tyrosine hydroxylase,
      synaptophysin and growth-associated protein-43 levels in the neonatal rat brain.
AB  - Methamphetamine (METH) is a most commonly abused drug which damages nerve
      terminals by causing formation of reactive oxygen species (ROS), apoptosis, and
      finally neuronal damage. Fetal exposure to neurotoxic METH causes significant
      behavioral effects. The developing fetus is substantially deficient in most
      antioxidative enzymes, and may therefore be at high risk from both endogenous and
      drug-enhanced oxidative stress. Little is known about the effects of METH on
      vesicular proteins such as synaptophysin and growth-associated protein 43 (GAP
      43) in the immature brain. The present study attempted to investigate the effects
      of METH-induced neurotoxicity in the dopaminergic system of the neonatal rat
      brain. Neonatal rats were subcutaneously exposed to 5-10mg/kg METH daily from
      postnatal day 4-10 for 7 consecutive days. The results showed that tyrosine
      hydroxylase enzyme levels were significantly decreased in the dorsal striatum,
      prefrontal cortex, nucleus accumbens and substantia nigra, synaptophysin levels
      decreased in the striatum and prefrontal cortex and growth-associated protein-43
      (GAP-43) levels significantly decreased in the nucleus accumbens of neonatal
      rats. Pretreatment with 2mg/kg melatonin 30 min prior to METH administration
      prevented METH-induced reduction in tyrosine hydroxylase, synaptophysin and
      growth-associated protein-43 protein levels in different brain regions. These
      results suggest that melatonin provides a protective effect against METH-induced
      nerve terminal degeneration in the immature rat brain probably via its
      antioxidant properties.

PMID- 19409440
TI  - Skin sensitization and possible groupings for 'read across' for rosin based
      substances.
AB  - A series of chemically modified rosin resins have been tested for their potential
      to cause skin sensitization using the mouse LLNA. Where direct comparative
      evidence is available, the results of the mouse LLNA are consistent with
      previously obtained data using the GPMT. Reactions with sufficient fumaric acid
      or maleic anhydride lead to maleopimaric acid anhydride (an acid anhydride), and
      give a clear response of a strong sensitizer that definitely requires
      classification. This sensitization is probably immunologically distinct from that
      claimed for oxidized rosin. Esterification will deactivate acid anhydrides formed
      from reacting rosin with maleic anhydride or fumaric acid. However, with maleic
      anhydride, there remains material capable of inducing a marginal (but
      classifiable under current criteria) immune response after the rosin had been
      maleinated and esterified. If proposed potency criteria are used these substances
      would not be considered 'strong sensitizers'. This response may be a function of
      a greater solubility in vehicle of the esterified maleinated (or fumarated) rosin
      over directly esterified material. Solubility limitations in the case of gum
      rosin directly esterified with pentaerythritol mean that it is not classifiable.
      Decarboxylated rosin and the glycerol ester of tall oil rosin are adequately
      soluble, and are not classifiable according to EU criteria. Polymers formed from
      rosin are also not classifiable as sensitizers. These studies confirm the value
      of grouping substances for 'read across' and the groupings chosen under the US
      EPA High Production Volume (HPV) Challenge Program. They also confirm the
      difficulties involved in dealing scientifically when examining the problem of
      skin sensitization associated with rosin related substances whilst still meeting
      current EU regulatory criteria.

PMID- 19409441
TI  - Acute benzodiazepine administration induces changes in homocysteine metabolism in
      young healthy volunteers.
AB  - PURPOSE: High cortisol plasma concentrations have been shown to be associated
      with increases in homocysteine levels. Here we studied whether decreases in
      cortisol concentration, induced by an acute oral dose of a benzodiazepine, could
      decrease homocysteine, and if changes were similar in both genders. METHODS: This
      was a double-blind, cross-over design study of acute oral flunitrazepam (1.2 mg)
      and placebo in young, healthy, male and female (n=21) volunteers. Blood samples
      were collected 3 h after ingestion (after peak-plasma concentration of
      flunitrazepam was reached). Various biochemical parameters were analysed, such as
      plasma homocysteine, cysteine, folate, vitamins B6, B12, and sexual hormones.
      RESULTS: Flunitrazepam reduced cortisol (p=0.0011), cysteine (p=0.014) and
      homocysteine (p=0.028) concentrations, irrespective of gender. No correlations
      were found between cortisol and other biochemical markers (all r's<0.03).
      Concentration of cysteine and homocysteine were negatively correlated with plasma
      flunitrazepam concentration, suggesting that changes in these amino acids might
      be related to the metabolism of this benzodiazepine. CONCLUSION: Acute
      administration of flunitrazepam decreases plasma homocysteine and cysteine by
      mechanisms that seem unrelated to changes in cortisol. Given the importance of
      homocysteine as a marker of life-threatening disorders, the mechanisms involved
      in the decrease of these amino acids are potential targets for clinical
      application.

PMID- 19409442
TI  - Chronic equol administration attenuates the antioxidant defense system and causes
      apoptosis in the mouse brain.
AB  - We investigated the effects of equol on the antioxidant defense system and
      apoptosis in the brains of mice administered equol at 5 or 25mg/kg BW for 3 or 7
      weeks. The effects of equol on the antioxidant defense system differed with the
      administration conditions. At 3 weeks, equol significantly inhibited lipid
      peroxidation and increased the catalase and total SOD activity in a dose
      dependent manner, although equol did not have much effect on the GSH-related
      system. Following equol administration for 7 weeks, the level of TBARS was
      increased, while the catalase and total SOD activity were attenuated, although
      the difference was significant only at the higher dose. Moreover, at the higher
      dose, equol significantly downregulated the GSH-related defense system. The
      GSH/GSSG ratio was decreased in a dose-dependent manner, as was the GSH-px and GR
      activity. As a result of these changes, apoptosis was induced in the mouse brain
      at both doses. The apoptosis process in the brain triggered by equol at the
      higher dose was consistent with a report that equol leads to apoptosis via p53
      activation in vitro. Based on our results, chronic equol administration at a
      higher dose may disrupt the antioxidant defense system and induce apoptosis in
      the mouse brain.

PMID- 19409443
TI  - Decreased nitric oxide markers and morphological changes in the brain of arsenic
      exposed rats.
AB  - Epidemiological studies demonstrate an association between chronic consumption of
      arsenic contaminated water and cognitive deficits, especially when the exposure
      takes place during childhood. This study documents structural changes and
      nitrergic deficits in the striatum of adult female Wistar rats exposed to arsenic
      in drinking water (3 ppm, approximately 0.4 mg/kg per day) from gestation,
      throughout lactation and development until the age of 4 months. Kainic acid
      injected animals (10mg/kg, i.p.) were also analyzed as positive controls of
      neural cell damage. Morphological characteristics of cells, fiber tracts and
      axons were analyzed by means of light microscopy as well as immunoreactivity to
      neuronal nitric oxide synthase (nNOS). As nitrergic markers, nitrite/nitrate
      concentrations, nNOS levels and expression of nNOS-mRNA were quantified in
      striatal tissue. Reactive oxygen species (ROS) and lipid peroxidation (LPx) were
      determined as oxidative stress markers. Arsenic exposure resulted in moderate to
      severe alterations of thickness, organization, surrounding space and shape of
      fiber tracts and axons, while cell bodies remained healthy. These anomalies were
      not accompanied by ROS and/or LPx increases. By contrast, except the expression
      of nNOS-mRNA, all nitrergic markers including striatal nNOS immunoreactivity
      presented a significant decrease. These results indicate that arsenic targets the
      central nitrergic system and disturbs brain structural organization at low
      exposure levels.

PMID- 19409444
TI  - Heavy metal uranium affects the brain cholinergic system in rat following sub
      chronic and chronic exposure.
AB  - Uranium is a heavy metal naturally present in the environment that may be
      chronically ingested by the population. Previous studies have shown that uranium
      is present in the brain and alters behaviour, notably locomotor activity,
      sensorimotor ability, sleep/wake cycle and the memory process, but also
      metabolism of neurotransmitters. The cholinergic system mediates many cognitive
      systems, including those disturbed after chronic exposure to uranium i.e.,
      spatial memory, sleep/wake cycle and locomotor activity. The objective of this
      study was to assess whether these disorders follow uranium-induced alteration of
      the cholinergic system. In comparison with 40 control rats, 40 rats drank 40 mg/L
      uranyl nitrate for 1.5 or 9 months. Cortex and hippocampus were removed and gene
      expression and protein level were analysed to determine potential changes in
      cholinergic receptors and acetylcholine levels. The expression of genes showed
      various alterations in the two brain areas after short- and long-term exposure.
      Nevertheless, protein levels of the choline acetyltransferase enzyme (ChAT), the
      vesicular transporter of acetylcholine (VAChT) and the nicotinic receptor beta2
      sub-unit (nAChRbeta2) were unmodified in all cases of the experiment and
      muscarinic receptor type 1 (m1AChR) protein level was disturbed only after 9
      months of exposure in the cortex (-30%). Acetylcholine levels were unchanged in
      the hippocampus after 1.5 and 9 months, but were decreased in the cortex after
      1.5 months only (-22%). Acetylcholinesterase (AChE) activity was also unchanged
      in the hippocampus but decreased in the cortex after 1.5 and 9 months (-16% and 
      18%, respectively). Taken together, these data indicate that the cholinergic
      system is a target of uranium exposure in a structure-dependent and time
      dependent manner. These cholinergic alterations could participate in behavioural
      impairments.

PMID- 19409446
TI  - Characteristics of ATP-activated current in nodose ganglion neurons of rats.
AB  - The characteristics of ATP-activated currents (I(ATP)) in rat nodose ganglion
      (NG) neurons have not been fully clarified. Especially, the correlation between
      I(ATP) phenotype and P2X receptor subunit genotype in rat NG neuron is not clear.
      By whole-cell patch-clamp and single cell immunocytochemical techniques, we
      explored the characteristics of the I(ATP) phenotype and its correlation with P2X
      receptor subunits in acutely isolated NG neuron of rats. The results indicated
      that I(ATP) of NG neurons can be classified into four types: F type (fast type,
      8.1%), I type (intermediate type, 14.8%), S type (slowing type, 37.0%) and vS
      type (very slowing type, 21.5%). The single immunocytochemical studies have
      demonstrated that F type cells express P2X1 and P2X3 subunits, I type cells P2X1,
      P2X3 and P2X4 subunits, S type cells P2X1, P2X2 and P2X3 subunits and vS type
      cells P2X2, P2X3 and P2X4 subunits. The results reveal that there are four types
      of I(ATP) in NG neurons, differential expression of distinct P2X subunits may
      underlie the I(ATP) phenotype.

PMID- 19409445
TI  - Modeling of glycolytic wave propagation in an open spatial reactor with
      inhomogeneous substrate influx.
AB  - The spatio-temporal dynamics of traveling waves in glycolysis as it occurs in
      yeast extract have been studied, both theoretically and experimentally. We
      describe this phenomenon with the distributed Selkov model that accounts for the
      reactions of phosphofructokinase, which is a key enzyme of the glycolytic
      reaction cascade. To describe the experimentally observed phase waves in an open
      spatial reactor we introduce a non-homogeneous flux of substrate in the model.
      The experimental observation that waves can change their direction of propagation
      during the experiment is considered in the model. The mechanism for such a change
      in wave direction is discussed.

PMID- 19409447
TI  - Apolipoprotein E modulates auditory event-related potentials in healthy aging.
AB  - 42 individuals ranging from 47 to 73 years of age underwent an auditory three
      stimulus oddball task while their event-related potentials (ERPs) were recorded.
      Half were APOE epsilon3 homozygotes and the remaining participants were either
      epsilon3/epsilon4 heterozygotes (n=13), or epsilon4 homozygotes (n=8). Analyses
      of variance showed that the heterozygotes had lower N1 amplitudes than the
      epsilon3 homozygotes, consistent with a previous study of participants with mild
      cognitive impairment (MCI) [I. Reinvang, T. Espeseth, L. Gjerstad, Cognitive ERPs
      are related to ApoE allelic variation in mildly cognitively impaired patients,
      Neuroscience Letters 382 (3) (2005) 346-351]. APOE genotype also significantly
      modulated N2 latency. epsilon4 homozygotes had longer N2 latencies, and
      importantly, longer N2 latencies predicted decline in verbal learning after 3.5
      years follow up. These findings indicate a potential clinical significance of
      individual differences in ERP components N1 and N2.

PMID- 19409448
TI  - Characterization of temperature dependent and substrate-binding cleft movements
      in Bacillus circulans family 11 xylanase: a molecular dynamics investigation.
AB  - BACKGROUND: Xylanases (EC 3.2.1.8) hydrolyze xylan, one of the most abundant
      plant polysaccharides found in nature, and have many potential applications in
      biotechnology. METHODS: Molecular dynamics simulations were used to investigate
      the effects of temperature between 298 to 338 K and xylobiose binding on residues
      located in the substrate-binding cleft of the family 11 xylanase from Bacillus
      circulans (BcX). RESULTS: In the absence of xylobiose the BcX exhibits
      temperature dependent movement of the thumb region which adopts an open
      conformation exposing the active site at the optimum catalytic temperature (328
      K). In the presence of substrate, the thumb region restricts access to the active
      site at all temperatures, and this conformation is maintained by
      substrate/protein hydrogen bonds involving active site residues, including
      hydrogen bonds between Tyr69 and the 2' hydroxyl group of the substrate.
      Substrate access to the active site is regulated by temperature dependent motions
      that are restricted to the thumb region, and the BcX/substrate complex is
      stabilized by extensive intermolecular hydrogen bonding with residues in the
      active site. GENERAL SIGNIFICANCE: These results call for a revision of both the
      "hinge-bending" model for the activity of group 11 xylanases, and the role of
      Tyr69 in the catalytic mechanism.

PMID- 19409449
TI  - The role of advanced glycation end products in retinal ageing and disease.
AB  - The retina is exposed to a lifetime of potentially damaging environmental and
      physiological factors that make the component cells exquisitely sensitive to age
      related processes. Retinal ageing is complex and a raft of abnormalities can
      accumulate in all layers of the retina. Some of this pathology serves as a
      sinister preamble to serious conditions such as age-related macular degeneration
      (AMD) which remains the leading cause of irreversible blindness in the Western
      world. The formation of advanced glycation end products (AGEs) is a natural
      function of ageing but accumulation of these adducts also represents a key
      pathophysiological event in a range of important human diseases. AGEs act as
      mediators of neurodegeneration, induce irreversible changes in the extracellular
      matrix, vascular dysfunction and pro-inflammatory signalling. Since many cells
      and tissues of the eye are profoundly influenced by such processes, it is fitting
      that advanced glycation is now receiving considerable attention as a possible
      pathogenic factor in visual disorders. This review presents the current evidence
      for a pathogenic role for AGEs and activation of the receptor for AGEs (RAGE) in
      initiation and progression of retinal disease. It draws upon the clinical and
      experimental literature and highlights the opportunities for further research
      that would definitively establish these adducts as important instigators of
      retinal disease. The therapeutic potential for novel agents that can ameliorate
      AGE formation of attenuate RAGE signalling in the retina is also discussed.

PMID- 19409450
TI  - Translating preclinical findings of (endothelial) progenitor cell mobilization
      into the clinic; from bedside to bench and back.
AB  - It is generally accepted that angiogenesis plays a major role in tumor growth and
      numerous targeting agents directed against angiogenesis pathways have been
      developed and approved for clinical use. In the past years the concept of
      angiogenesis has developed into a multi-faceted process in which, besides local
      activation and division of endothelial cells, bone marrow derived progenitor
      cells (BMDPCs) contribute to neovascularization. A multitude of preclinical and
      clinical data indicates that the release of BMDPCs influences the response to
      certain anti-cancer modalities. In this review we provide an overview of all the
      preclinical and clinical studies contributing to this hypothesis and translate
      these findings to the clinic by pointing out the clinical implications these
      findings might have. The recent insight in the mechanism of a systemic host
      response, in response to various treatment modalities has shed new light on the
      mechanism of tumor regrowth, early recurrence and metastasis formation during or
      after treatment. This provides various new targets for therapy which can be used
      to improve conventional chemotherapy. Furthermore it provides a potential
      explanation why bevacizumab selectively enhances the effectiveness of only
      certain types of chemotherapy.

PMID- 19409451
TI  - Pannexin1 in the outer retina of the zebrafish, Danio rerio.
AB  - In the retina, chemical and electrical synapses couple neurons into functional
      networks. New candidates encoding for electrical synapse proteins have recently
      emerged. In the present study, we determined the localization of the candidate
      protein pannexin1 (zfPanx1) in the zebrafish retina and studied the functional
      properties of zfPanx1 exogenously expressed in Neuroblastoma 2a (N2a) cells.
      zfPanx1 was identified on the surface of horizontal cell dendrites invaginating
      deeply into the cone pedicle near the glutamate release sites of the cones,
      providing in vivo evidence for hemichannel formation at that location. This
      strategic position of zfPanx1 in the photoreceptor synapse could potentially
      allow modulation of cone output. Using whole cell voltage clamp and excised patch
      recordings of transfected N2a cells, we demonstrated that zfPanx1 forms voltage
      activated hemichannels with a large unitary conductance in vitro. These channels
      can open at physiological membrane potentials. Functional channels were not
      formed following mutation of a single amino acid within a conserved protein motif
      recently shown to be N-glycosylated in rodent Panx1. Together, these findings
      indicate that zfPanx1 displays properties similar to its mammalian homologues and
      can potentially play an important role in functions of the outer retina.

PMID- 19409453
TI  - Brain creatine kinase activity after meningitis induced by Streptococcus
      pneumoniae.
AB  - Bacterial meningitis due to Streptococcus pneumoniae is associated with a
      significant mortality rate and persisting neurologic sequelae including sensory
      motor deficits, seizures, and impairments of learning and memory. Creatine kinase
      (CK) is an effective buffering system of cellular ATP levels in high-energy
      consuming tissues; a decrease in CK activity is associated with a
      neurodegenerative pathway that results in neuronal loss. Thus, the aim of this
      study was to evaluate brain CK activity after pneumococcal meningitis. The
      animals underwent a magna cistern tap receiving either sterile saline as a
      placebo or an equivalent volume of a S. pneumoniae suspension; they were killed
      6, 12, 24 and 48h after that, the brain was removed and hippocampus, striatum,
      cerebellum, cerebral cortex and prefrontal cortex were dissected and used for the
      determination of CK activity. We verified that CK activity was not altered 6 and
      12h after meningitis. Interestingly, 24h after the induction of the meningitis we
      observed a decrease in CK activity. Finally, CK activity was not altered 48h
      after meningitis. Although it is difficult to extrapolate our findings to the
      human condition, the inhibition of brain CK activity may be involved in the
      pathogenesis of pneumococcal meningitis.

PMID- 19409452
TI  - Endothelin-1 raises excitability and reduces potassium currents in sensory
      neurons.
AB  - Exposure to endothelin-1 (ET-1, 50 nM) of sensory neurons, acutely isolated from
      rat dorsal root ganglia (DRG), results in an increase in the number of action
      potentials elicited by a linear ramp of stimulating current. The changes are
      complete in 5 min after ET-1 treatment and do not reverse in 5-10 min after ET
      1's removal. Neither the resting potential, nor the threshold potential for the
      first or second action potentials, nor their rate-of-rise or decay, are changed
      by ET-1 exposure, but the slow depolarizations which occur before the first and
      second action potentials during the current ramp are increased by ca. 50% by ET
      1. The delayed rectifier type of K(+) currents (I(K)), measured under whole-cell
      voltage clamp, are depressed by approximately 30% during such exposure to ET-1.
      The voltage-dependent gating of steady-state I(K) and the current kinetics are
      unchanged by ET-1, leaving the sole effect as a drop in the number of available
      channels. I(K) is affected by ET-1 only in Isolectin B(4)-positive cells,
      suggesting that there may be a selective action in enhancing impulse activity on
      this class of nociceptive neuron. This decrease in I(K) will potentiate the
      excitability-inducing actions of the previously reported negative shift in
      tetrodotoxin-resistant Na(+) channel gating in such neurons.

PMID- 19409455
TI  - Induction of habits in rats by a forced-choice procedure in T-maze and the effect
      of pre-test free exploration.
AB  - A forced-choice procedure in T-maze designed for the induction of habits was used
      to induce strong habits in rats. The response choices of rats in 20 free-choice
      trials were compared after the rats had been subjected to 1 or 200 forced-choice
      trials to one side of the T-maze. After 200 forced-choice trials the rats showed
      a significant (p<.001) propensity for the habitual arm of the maze in the
      subsequent free-choice trials. The habit was at least as pronounced when analysed
      over the last 10 free-choice trials as when it was analysed over the first 10
      free-choice trials. When the rats were given the opportunity to explore the
      entire maze immediately before the free-choice challenge after 200 forced-choice
      trials, this resulted in a large variation in the choice pattern of the
      individual rats, and a subgroup of rats choose the newly opened maze arm in 95
      100% of the 20 free-choice trials.

PMID- 19409454
TI  - Caffeic and chlorogenic acids in Ilex paraguariensis extracts are the main
      inhibitors of AGE generation by methylglyoxal in model proteins.
AB  - The present study concentrates on the evaluation of the anti-glycation effect of
      some bioactive substances present in yerba mate (Ilex paraguariensis): 5
      caffeoylquinic acid, caffeic acid and a sapogenin (oleanolic acid). Bovine serum
      albumin and histones were incubated in the presence of methylglyoxal with or
      without the addition of 5-caffeoylquinic acid, caffeic acid and oleanolic acid.
      After the incubation period, advanced glycation end product (AGE) fluorescence
      spectra were performed and protein structural changes were evaluated by Sodium
      Dodecyl Sulfate Polyacrylamide Gel Electrophoresis. Chlorogenic acid, caffeic
      acid are the main substances responsible for the anti-glycation effect of mate
      tea.

PMID- 19409456
TI  - The effects of prior weight reduction on the running wheel-induced feeding
      suppression in rats.
AB  - Adult male rats given ad lib access to food and a running wheel show an initial
      feeding and weight suppression. Over 6-10 days feeding recovers, but body weight
      remains low. It is not clear which effect is primary, the wheel-induced feeding
      or weight change. To test this, rats were first restricted to 15g of food a day
      for 8 or 16 days to reduce their weight relative to control non-restricted rats.
      They were then returned to ad lib feeding and half the restricted and non
      restricted control rats were introduced to the wheel either immediately
      (Experiment 1) or 4 days later (Experiment 2). Food intake, body weight, and
      wheel running were monitored throughout the experiments. At the return to ad lib
      feeding, prior food restriction elevated feeding. Both immediate and delayed
      wheel access suppressed feeding in both groups of wheel access rats compared to
      the appropriate control rats. Feeding history did not have a significant effect
      on wheel running. The wheel-induced reductions in feeding from baseline were
      similar in the weight reduced and normal weight animals suggesting that prior
      weight restriction did not prevent the onset of the wheel-induced feeding
      suppression. It is therefore suggested that the feeding suppression is not driven
      by a reduced weight set point.

PMID- 19409457
TI  - Aspartic proteases gene family in rice: Gene structure and expression, predicted
      protein features and phylogenetic relation.
AB  - Aspartic proteases constitute a large family in eukaryotes, which play
      fundamental roles in protein processing, maturation and degradation. In this
      study, we identified 96 OsAP genes in rice (Oryza sativa L.), the model plant for
      monocots, by a reiterative database search. The analysis of the complete set of
      OsAP genes is presented, including chromosomal location, phylogenetic
      relationships, classification and gene structure. Moreover, a comprehensive
      expression analysis of OsAP family genes was performed using 24 tissues during
      the plant life cycle of two rice cultivars. Sixty-six OsAP genes were found to be
      expressed in at least one of the examined developmental stages, which were
      divided into 3 classes based on their transcript levels. OsAP genes were also
      found to be differentially up- or down-regulated in rice seedlings in response to
      treatments with phytohormones, as well as in plumules/radicles under light/dark
      conditions. The comprehensive annotation and expression profiling undertaken in
      this research add to our understanding of OsAP family genes in rice growth and
      development. Our results also provide a basis for selection of candidate genes
      for functional validation in future studies.

PMID- 19409459
TI  - Effects of postnatal exposure to methylmercury on spatial learning and memory and
      brain NMDA receptor mRNA expression in rats.
AB  - The extreme vulnerability of developing nervous system to methylmercury (MeHg) is
      well documented. Still unclear is the consequence of different postnatal period
      exposure to MeHg. We investigated the critical postnatal phase when MeHg induced
      neurotoxicity in rats and the underlying mechanism. Rats were given 5mg/(kg day)
      methylmercury chloride (MMC) orally on postnatal day (PND) 7, PND14, PND28, and
      PND60 for consecutive 7 days. A control group was treated with 0.9% sodium
      chloride solution 5 ml/(kg day) instead. On PND69, spatial learning and memory
      was evaluated by Morris water maze test. Behavior deficits were found in MMC
      treated rats of PND7 and PND14 groups (p<0.01). N-methyl-D-aspartate (NMDA)
      receptor 2 subunits mRNA expressions were evaluated 3 days after the last
      administration. In hippocampus, the mRNA expression of NR2A and NR2B decreased,
      but the NR2C expression increased in PND14 group following MMC-treatment
      (p<0.01). In cerebral cortex, mRNA expression of NR2A decreased, with NR2C
      expression elevating in PND14 group following MMC-treatment (p<0.05). These
      observations suggest that the postnatal exposure to MeHg during PND7-20 could
      cause neurobehavioral deficits which extend to adulthood. Furthermore, the
      abnormal expression of NMDAR 2 subunits might associate with the impairment.

PMID- 19409458
TI  - Dynamic changes in DNA methylation during multistep rat lung carcinogenesis
      induced by 3-methylcholanthrene and diethylnitrosamine.
AB  - 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN) are typical genotoxic
      carcinogens that can induce tumors in a variety of human and rodent tissues.
      However, the epigenetic mechanisms underlying their tumorigenesis are unclear. In
      this study we used a MCA/DEN-induced multistep lung carcinogenesis rat model to
      study the evolution of alterations in DNA methylation. Rats were treated with a
      single dose of MCA and DEN in iodized oil by left intra-bronchial instillation.
      The animals were killed on days 15, 35, 55, 65 and 75 and samples of various
      pathological phases during carcinogenesis were obtained on these days. The status
      of global methylation was analyzed for each sample using a monoclonal antibody
      specific for 5-methycytosine (5-mC) and quantified by image analysis software. We
      found that the degree of global methylation was, in general, higher in basal
      cells compared to luminal cells of normal, precancerous and tumor tissues. The
      combined 5-mC scores of different types of tissues decreased gradually during the
      progression of carcinogenesis. We also used methylation-sensitive arbitrarily
      primed PCR (MS-AP-PCR) to screen a total of eight differentially methylated DNA
      fragments in both precancerous and tumor tissues isolated using laser capture
      microdissection (LCM), and observed that both unique hypomethylation and
      hypermethylation fragments coexist after exposure to genotoxic carcinogens.
      Remarkably, epigenetic alterations in p16 (CDKN2A), but not in p15 (CDKN2B), were
      observed, and these correlated with the presence of pathologic lung lesions and
      loss of p16 protein expression. Moreover, defective expression of p16 in
      methylated primary tumor cell lines recovered markedly after treated with 5-aza
      2'-deoxycytidine (5-aza-dC). These results suggest that DNA methylation
      alterations are an early event in tumorigenesis and play an important role during
      MCA/DEN-induced multistep rat lung carcinogenesis.

PMID- 19409460
TI  - Development of PMMA membranes functionalized with hydroxypropyl-beta
      cyclodextrins for controlled drug delivery using a supercritical CO(2)-assisted
      technology.
AB  - Cyclodextrin-containing polymers have proved themselves to be useful for
      controlled release. Herein we describe the preparation of membranes of
      poly(methylmethacrylate) (PMMA) containing hydroxypropyl-beta-cyclodextrins (HP
      beta-CDs) using a supercritical CO(2)-assisted phase inversion method, for
      potential application as drug delivery devices. Results are reported on the
      membrane preparation, physical properties, and drug elution profile of a model
      drug. The polymeric membranes were obtained with HP-beta-CD contents ranging from
      0 to 33.4 wt%, by changing the composition of the casting solution, and were
      further impregnated with ibuprofen using supercritical carbon dioxide (scCO(2))
      in batch mode. The influence of the membrane functionalization in the controlled
      release of ibuprofen was studied by performing in vitro experiments in buffer
      solution pH at 7.4. The release of the anti-inflammatory drug could be tuned by
      varying the cyclodextrin content on the membranes.

PMID- 19409461
TI  - Synthesis, characterization, drug-loading capacity and safety of novel octyl
      modified serum albumin micelles.
AB  - A novel albumin derivative octyl modified serum albumin (OSA) which can form a
      core-shell structure in aqueous media by self-assembling due to core segregation
      and a combination of intermolecular forces has been synthesized. The chemical
      structure and physical properties of OSA were characterized by FTIR, (1)H NMR and
      TG. The degree of substitution (DS) was in the range of 52.4-69.7% and 48.9-65.8%
      determined by elemental analysis and fluorescamine assay, respectively. With the
      increase in the DS of octyl group, the critical micelle concentration (CMC)
      decreased from 30.1 to 14.7 mg/L because of the increasing hydrophobicity. In the
      light of the hydrophobic core as a microreservoir for poorly water-soluble drugs,
      paclitaxel (PTX) was successfully loaded into OSA micelles by the dialysis method
      with a high drug-loading (33.1 wt%) and entrapment efficiency (90.5%) due to the
      synergistic effect of micellar encapsulation and binding interaction between drug
      and OSA. Compared with PTX-loaded unmodified BSA preparation, PTX-loaded OSA
      micelles are characterized by small size, narrow size distribution, great drug
      loading capacity and enhanced stability. The size of PTX-loaded micelles was in
      the range of 123.3-152.8 nm and smaller than their corresponding blank micelles.
      Hemolysis and cytotoxicity studies showed that OSA was safer than Tween-80 and
      Cremophor EL as an injectable pharmaceutic adjuvant for PTX. In terms of the
      greater drug-loading capacity and safer character, the novel albumin derivative
      OSA is a prospective injectable delivery system for PTX.

PMID- 19409462
TI  - Nanoparticle formation from probucol/PVP/sodium alkyl sulfate co-ground mixture.
AB  - Nanoparticles of a poorly water-soluble drug, probucol, have been obtained by co
      grinding with PVP and SDS. The purpose of this study was to investigate the
      effect of the alkyl chain length of sodium alkyl sulfates (CnS, n=6, 8, 12, 16
      and 18) on probucol nanoparticle formation. From the results of particle size
      determination and quantitative measurement of nanoparticle fraction of probucol
      by HPLC, it was found that the alkyl chain length of the sodium alkyl sulfate
      affected the probucol nanoparticle formation. The efficiency, based on the
      quantitative determination of nanoparticles, was in the order:
      C18S>C16S>C12S>C8S>C6S. Probucol nanoparticles of less than 800 nm were
      effectively produced (more than 95%) with the increase of the amount of
      surfactants. (13)C solid-state NMR of co-ground mixtures showed a new peak
      originating from the probucol interaction with PVP together with the existence of
      probucol crystal peaks. Excess amounts of surfactants were expected to play an
      important role for stabilizing the probucol nanoparticles in the suspension via
      the electrostatic repulsive effect.

PMID- 19409463
TI  - Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: formulation,
      optimization and in vitro characterization.
AB  - The objective of this study was to optimize and characterize a novel polymeric
      mixed micelle composed of Pluronic P123 and F127 loaded with paclitaxel (PTX). A
      Doehlert matrix design was utilized to investigate the effect of four variables,
      namely P123 mass fraction, amount of water, feeding of PTX and hydration
      temperature on the responses including drug-loading coefficient (DL %),
      encapsulation ratio (ER %) and the percentage of PTX precipitated from the drug
      loaded mixed micelles after 48 h at 37 (PTX precipitated %) for improvement of
      drug solubilization efficiency and micelle stability. PTX-loaded P123/F127 mixed
      micelles were prepared by thin-film hydration method. The optimized formulation
      showed a particle size of about 25 nm with ER %>90%, and a sustained release
      behavior compared to Taxol. Micelle formation was confirmed by NMR spectroscopy.
      The mixed micelles had a low CMC of 0.0059% in water. In addition, micelle
      stability studies implied that introduction of Pluronic F127 (33 wt%) into P123
      micelle system significantly increased the stability of PTX-loaded micelles. More
      importantly, in vitro cytotoxicity was assessed using human lung adenocarcinoma
      cell lines SPC-A1 and A-549 and was compared to Taxol and the free drug. The cell
      viability assay against A-549 cells exhibited the 50% inhibition concentration
      (IC50) of PTX-loaded P123/F127 mixed micelles (0.1 microg/ml) was much lower than
      those of Taxol injection (0.4 microg/ml) and the free PTX (1.7 microg/ml).
      Therefore, PTX-loaded P123/F127 mixed micelles may be considered as an effective
      anticancer drug delivery system for cancer chemotherapy.

PMID- 19409464
TI  - Micronization of silybin by the emulsion solvent diffusion method.
AB  - Micronized silybin particles were successfully prepared by emulsion solvent
      diffusion method. Uniform spherical and rod-shaped particles with a mean size of
      2.48 and 0.89 microm could be obtained using sodium dodecyl sulfate (SDS)
      concentration of 0.1 wt% at 30 and 15 degrees C, respectively. The
      characterization of silybin particles by SEM and particle size distribution (PSD)
      indicated that with the increase of temperature from 15 to 30 degrees C, the as
      prepared particles became bigger and had a tendency to turn into spherical
      shapes; with the increase of SDS concentration from 0.02 to 0.1 wt%, the span of
      PSD became narrower while the mean particle size kept almost unchanged. XRD
      patterns and FT-IR spectra showed that the spherical and rod-shaped silybin
      particles possessed decreased crystallinity; however, the chemical structure and
      components were similar to those of the commercial silybin powder. Dissolution
      tests demonstrated that both of the spherical and rod-shaped silybin particles
      exhibited significantly enhanced dissolution rate when compared to the commercial
      silybin powder.

PMID- 19409466
TI  - Liposomal dexamethasone-diclofenac combinations for local osteoarthritis
      treatment.
AB  - Conventional chronic and acute treatments for osteoarthritis (OA) are by oral
      NSAIDs (such as diclofenac) and intra-articular injected glucocorticosteroids
      (such as dexamethasone). In free form, diclofenac and dexamethasone generate
      severe adverse effects with risks of toxicity. To reduce these drawbacks, we
      investigated local injections of liposomal formulations for diclofenac and
      dexamethasone (each alone, and their combination). Bioadhesive liposomes carrying
      hyaluronan (HA-BAL) or collagen (COL-BAL) as their surface-anchored ligand were
      used for the task. Each drug alone or their combination showed high efficiency
      encapsulations (> or =80%) and performance as slow-release depots (half-lives in
      the range of 1-3 days under the fastest conditions). Employing RIA and immunoblot
      assay techniques, it was verified that the encapsulated drugs retained their
      biological activities: inhibitions of Cyclooxygenases enzyme-activity
      (diclofenac) and of Cyclooxygenases protein-expression (dexamethasone). Using
      live-animal MRI, a single intra-articular injection of each liposome-drug(s)
      formulation sufficed to reduce knee joint inflammation in OA rats over a time
      span of 17 days, HA-BAL better than COL-BAL. The most effective treatment was by
      the combination of both drugs in HA-BAL, a single dose reducing the inflammation
      volume down to 12.9% from initial over that time span. We find all three HA-BAL
      formulations worthy of further studies.

PMID- 19409465
TI  - A new micro/nanoencapsulated porphyrin formulation for PDT treatment.
AB  - The highly hydrophobic 5,10,15-triphenyl-20-(3-N-methylpyridinium-yl)porphyrin
      (3MMe) cationic species was synthesized, characterized and encapsulated in marine
      atelocollagen/xanthane gum microcapsules by the coacervation method. Further
      reduction in the capsule size, from several microns down to about 300-400 nm, was
      carried out successfully by ultrasonic processing in the presence of up to 1.6%
      Tween 20 surfactant, without affecting the distribution of 3MMe in the oily core.
      The resulting cream-like product exhibited enhanced photodynamic activity but
      negligible cytotoxicity towards HeLa cells. The polymeric micro/nanocapsule
      formulation was found to be about 4 times more phototoxic than the respective
      phosphatidylcholine lipidic emulsion, demonstrating high potentiality for
      photodynamic therapy applications.

PMID- 19409467
TI  - Hyperbranched polysiloxysilane nanoparticles: surface charge control of nonviral
      gene delivery vectors and nanoprobes.
AB  - New hyperbranched polysiloxysilane (HBPS) materials containing terminal
      carboxylic acid and quaternary ammonium groups were designed and synthesized to
      obtain fluorescent-dye-encapsulated nanoparticles. These polymers exhibited
      desirable characteristics, including amphiphilicity for nanoparticle formation,
      and contained various terminal groups for surface-charge control on the
      nanoparticles or for further bioconjugation for targeted imaging. Nanoprobes
      composed of polysiloxysilane nanoparticles encapsulating two-photon dyes were
      also prepared for optical bioimaging with controlled surface charge density (zeta
      potential) for modulation of cellular uptake. Intracellular delivery of these
      structurally similar polysiloxysilane nanoparticles, with substantially different
      surface charges, was investigated using confocal and two-photon fluorescence
      microscopy as well as flow cytometry. Finally, the use of these nanoparticles as
      efficient gene delivery vectors was demonstrated by means of in vitro
      transfection study using beta-galactosidase plasmid and pEGFP-N1 plasmid and the
      most efficient combination was obtained using HBPS-CN30:70.

PMID- 19409468
TI  - Lipid nanocapsules: a new platform for nanomedicine.
AB  - Nanomedicine, an emerging new field created by the fusion of nanotechnology and
      medicine, is one of the most promising pathways for the development of effective
      targeted therapies with oncology being the earlier and the most notable
      beneficiary to date. Indeed, drug-loaded nanoparticles provide an ideal solution
      to overcome the low selectivity of the anticancer drugs towards the cancer cells
      in regards to normal cells and the induced severe side-effects, thanks to their
      passive and/or active targeting to cancer tissues. Liposome-based systems
      encapsulating drugs are already used in some cancer therapies (e.g. Myocet,
      Daunoxome, Doxil). But liposomes have some important drawbacks: they have a low
      capacity to encapsulate lipophilic drugs (even though it exists), they are
      manufactured through processes involving organic solvents, and they are leaky,
      unstable in biological fluids and more generally in aqueous solutions for being
      commercialized as such. We have developed new nano-cargos, the lipid
      nanocapsules, with sizes below the endothelium fenestration (phi<100 nm), that
      solve these disadvantages. They are prepared according to a solvent-free process
      and they are stable for at least one year in suspension ready for injection,
      which should reduce considerably the cost and convenience for treatment.
      Moreover, these new nano-cargos have the ability to encapsulate efficiently
      lipophilic drugs, offering a pharmaceutical solution for their intravenous
      administration. The lipid nanocapsules (LNCs) have been prepared according to an
      original method based on a phase-inversion temperature process recently developed
      and patented. Their structure is a hybrid between polymeric nanocapsules and
      liposomes because of their oily core which is surrounded by a tensioactive rigid
      membrane. They have a lipoprotein-like structure. Their size can be adjusted
      below 100 nm with a narrow distribution. Importantly, these properties confer
      great stability to the structure (physical stability>18 months). Blank or drug
      loaded LNCs can be prepared, with or without PEG (polyethyleneglycol)ylation that
      is a key parameter that affects the vascular residence time of the nano-cargos.
      Other hydrophilic tails can also be grafted. Different anticancer drugs
      (paclitaxel, docetaxel, etoposide, hydroxytamoxifen, doxorubicin, etc.) have been
      encapsulated. They all are released according to a sustained pattern. Preclinical
      studies on cell cultures and animal models of tumors have been performed, showing
      promising results.

PMID- 19409469
TI  - Chitosan solutions and particles: evaluation of their permeation enhancing
      potential on MDCK cells used as blood brain barrier model.
AB  - It was the aim of the present study to investigate the potential of chitosan of
      different molecular weight in solution and as particles to enhance the transport
      into the brain. FITC-dextran 4 (FD4) transport with and without chitosans of
      different molecular weight across MDCK cell monolayers, a model for the blood
      brain barrier, was compared. In the following particles of chitosan exhibiting
      the most appropriate molecular weight were prepared and their particle size and
      stability were evaluated. Furthermore permeation studies, MDCK cell toxicity test
      and red blood cell lysis test were performed. The rank order for chitosan for
      permeation enhancement across MDCK cells was determined to be 20 kDa~150 kDa >
      400 kDa~600 kDa. Moreover particles showed a higher permeation enhancement than
      the corresponding solution and the smaller the particles were the higher the
      permeation of FD4 was. All particles were stable for 72 h. Particles displayed
      increased MDCK cell toxicity and red blood cell lysis compared to chitosan in
      solution. The smaller the particles were, the higher their toxicity was.
      According to these results chitosan particles are more potent in absorption
      enhancement than chitosan solutions.

PMID- 19409470
TI  - Effects of carriers on transgene expression from plasmids containing a DNA
      sequence with high histone affinity.
AB  - The intranuclear disposition of plasmid DNA is highly important for transgene
      expression. The effects of a left-handedly curved sequence with high histone
      affinity on transgene expression were examined in COS-7 cells with two kinds of
      carriers (Lipofectamine Plus and TransIT-LT1). Three plasmids containing the
      curved sequence at different positions were transfected. The transgene expression
      was affected by the position of the left-handedly curved sequence, and the
      sequence at appropriate locations enhanced the expression from plasmid DNAs.
      However, the position effects on the expression differed from those obtained by
      electroporation of the same plasmid DNAs in a naked form. In addition, the degree
      of expression enhancement seemed to depend on the carriers. These results suggest
      that the left-handedly curved sequence with high histone affinity could increase
      the transgene expression from a plasmid delivered with carriers.

PMID- 19409471
TI  - Facile fabrication of well-defined hydrogel beads with magnetic nanocomposite
      shells.
AB  - Well-defined magnetic nanocomposite beads with alginate gel cores and shells of
      iron oxide (gamma-Fe(2)O(3)) nanoparticles were prepared by self-assembly of
      colloidal particles at liquid-liquid interfaces and subsequent in situ gelation.
      Fe(2)O(3) nanoparticles could spontaneously adsorb onto the water droplet
      surfaces to stabilize water-in-hexane emulsions. Water droplets containing sodium
      alginate were in situ gelled by calcium cations, which were released from calcium
      ethylenediamine tetraacetic acid (Ca-EDTA) chelate by decreasing pH value through
      slow hydrolysis of d-glucono-delta-lactone (GDL). The resulting hybrid beads with
      a core-shell structure were easily collected by removing hexane. This facile and
      high efficient fabrication had a 100% yield and could be carried out at room
      temperature. Insulin microcrystal was encapsulated into the hybrid beads by
      dispersing them in the aqueous solution of alginate sodium in the fabrication
      process. The sustained release could be obtained due to the dual barriers of the
      hydrogel core and the close-packed inorganic shell. The release curves were
      nicely fitted by the Weibull equation and the release followed Fickian diffusion.
      The hybrid beads may find applications as delivery vehicles for biomolecules,
      drugs, cosmetics, food supplements and living cells.

PMID- 19409472
TI  - Capturing spatial attention with multisensory cues: a review.
AB  - The last 30 years have seen numerous studies demonstrating unimodal and
      crossmodal spatial cuing effects. However, surprisingly few studies have
      attempted to investigate whether multisensory cues might be any more effective in
      capturing a person's spatial attention than unimodal cues. Indeed, until very
      recently, the consensus view was that multisensory cues were, in fact, no more
      effective. However, the results of several recent studies have overturned this
      conclusion, by showing that multisensory cues retain their attention-capturing
      ability under conditions of perceptual load (i.e., when participants are
      simultaneously engaged in a concurrent attention-demanding task) while their
      constituent signals (when presented unimodally) do not. Here we review the
      empirical literature on multisensory spatial cuing effects and highlight the
      implications that this research has for the design of more effective warning
      signals in applied settings.

PMID- 19409473
TI  - Ethnopharmacological notes about ancient uses of medicinal plants in Tras-os
      Montes (northern of Portugal).
AB  - AIM OF THE STUDY: In order to preserve the ancestral knowledge, an
      ethnopharmacological study has been carried out in two councils belonging to Tras
      os-Montes region a small area located in the northern of Portugal. In that area,
      medicinal plants, most of the species wild, are still in use among farmers,
      shepherds and other people who live far from villages and built-up areas.
      MATERIALS AND METHODS: Among the 46 people that were interviewed (mean age of 66
      years old), 88 species belonging to 42 families of vascular plants were
      identified for treatment of various human ailments. An ethnopharmacological
      report is made consisting of species names, vernacular names, popular uses of the
      plants and their pharmacological properties. RESULTS AND CONCLUSION: The most
      dominant family is Lamiaceae (18%) and the most frequently part of the plant used
      for the treatment of diseases are leaves (37.9%). The largest number of taxa is
      used to treat gastrointestinal disorders (73.9%).

PMID- 19409474
TI  - In vitro anti-HIV activity of five selected South African medicinal plant
      extracts.
AB  - AIM OF THE STUDY: Five South African medicinal plants, Bulbine alooides (L.)
      Willd. (Asphodelaceae), Crinummacowani Baker (Amaryllidaceae), Hypoxis sobolifera
      var. sobolifera (Jacq.) Nel (Hypoxidaceae), Leonotisleonurus (L.) R.Br.
      (Lamiaceae) and Tulbaghiaviolacea Harv (Liliaceae) used for the treatment of
      various ailments, including infectious diseases, were screened for activity
      against human immunodeficiency virus (HIV). MATERIALS AND METHODS: Aqueous and
      ethanol extracts were tested for inhibitory activity in HIV-1 infected CEM.NK(R)
      CCR5 cells, and against HIV-1 reverse transcriptase (RT) and HIV-1 protease (PR).
      RESULTS: In CEM.NK(R)-CCR5 cells, ethanol extracts of Leonotisleonurus inhibited
      HIV-1 significantly (33% reduction in HIV-1 p24, P<0.05). HIV-1 RT inhibition (>
      or =50%) was shown for extracts of Bulbine alooides (aqueous and ethanol),
      Hypoxis sobolifera (aqueous and ethanol) and Leonotisleonurus (aqueous), but
      inhibitory activity was lost upon dereplication for removal of non-specific
      tannins/polysaccharides. HIV-1 PR inhibition was observed for extracts of Hypoxis
      sobolifera (aqueous), Bulbine alooides (aqueous and ethanol) and Leonotisleonurus
      (ethanol). Only ethanolic extracts of Bulbine alooides and Leonotisleonurus
      retained HIV-1 PR inhibition after dereplication with IC50 of 94 microg/ml and
      120 microg/ml, respectively. CONCLUSION: The dereplicated ethanolic extracts of
      Leonotisleonurus and Bulbine alooides showed the greatest anti-HIV potential in
      this study through inhibition of HIV-1 PR.

PMID- 19409475
TI  - Hachimijiogan (Ba-Wei-Di-Huang-Wan), a herbal medicine, improves unbalance of
      calcium metabolism in aged rats.
AB  - AIM OF THE STUDY: Aged animals as well as elderly humans commonly exhibit calcium
      (Ca) shortage because of increased Ca excretion into urine and decreased
      intestinal Ca absorption, which induce elevation of serum PTH levels to maintain
      serum Ca levels between a normal physiological range. The most important organ
      that regulates this Ca homeostasis is the kidney. Hachimijiogan (HJG), a
      traditional herbal medicine in Japan and China, has been used for treating
      clinical diseases associated with kidney dysfunctions in elderly humans. However,
      the mechanisms of its pharmacological actions remain to be understood poorly. The
      present study was designed to examine whether HJG improves age-related unbalance
      of Ca metabolism at the systemic level using aged rats. MATERIALS AND METHODS:
      HJG was administered to 21-month-old aged rats for 3 months, and several
      parameters associated with Ca metabolism in serum and urine were measured.
      RESULTS: Although HJG as well as aging itself did not affect serum Ca levels
      compared to young (11-week-old) rats, HJG improved increase in urinary Ca
      excretion and elevation of serum parathyroid hormone (PTH) levels in aged rats.
      However, HJG did not improve marked reduction of intestinal Ca absorption in aged
      rats. CONCLUSION: HJG showed regulating action for age-related unbalance of Ca
      metabolism at the systemic level. This finding would provide useful information
      for treating age-related several disorders associated with Ca unbalance.

PMID- 19409476
TI  - Ethnobotanical study on medicinal plants around Mt.Yinggeling, Hainan Island,
      China.
AB  - AIM OF THE STUDY: The main objectives were to collect information on the use of
      medicinal plants and compare medicinal plant traditions between Run and Qi.
      MATERIALS AND METHODS: Information was obtained from semi-structured interviews,
      personal conversation and guided fieldtrips with herbalists. RESULTS: 385 species
      belonging to 290 genera in 104 families were used for the treatment of various
      diseases. Rubiaceae (20 species), Euphorbiaceae and Compositae (19 species
      respectively) were predominant families used by herbalists. The most species were
      used for injuries (20.1%), muscular-skeletal system disorders (18.3%) and
      infections/infestations (18.0%). The coefficient of similarity (36.6%) shown a
      high consensus of plant species used by Run and Qi. The 'informant agreement
      ratio' values for both Run and Qi are rather low (less than 0.3). CONCLUSIONS:
      Traditional medicinal plants still play an important role in medical practices of
      Li Ethnic Group around Mt.Yinggeling. There is a close relationship of medicinal
      plant traditions between Run and Qi. Further investigation is necessary to record
      this valuable knowledge before its disappearance.

PMID- 19409477
TI  - Construction of combustion models for rapeseed methyl ester bio-diesel fuel for
      internal combustion engine applications.
AB  - Bio-diesel fuels are non-petroleum-based diesel fuels consisting of long chain
      alkyl esters produced by the transesterification of vegetable oils, that are
      intended for use (neat or blended with conventional fuels) in unmodified diesel
      engines. There have been few reports of studies proposing theoretical models for
      bio-diesel combustion simulations. In this study, we developed combustion models
      based on ones developed previously. We compiled the liquid fuel properties, and
      the existing detailed mechanism of methyl butanoate ester (MB, C(5)H(10)O(2))
      oxidation was supplemented by sub-mechanisms for two proposed fuel constituent
      components, C(7)H(16) and C(7)H(8)O (and then, by mp2d, C(4)H(6)O(2) and propyne,
      C(3)H(4)) to represent the combustion model for rapeseed methyl ester described
      by the chemical formula, C(19)H(34)O(2) (or C(19)H(36)O(2)). The main fuel vapor
      thermal properties were taken as those of methyl palmitate C(19)H(36)O(2) in the
      NASA polynomial form of the Burcat database. The special global reaction was
      introduced to "crack" the main fuel into its constituent components. This general
      reaction included 309 species and 1472 reactions, including soot and NO(x)
      formation processes. The detailed combustion mechanism was validated using shock
      tube ignition-delay data under diesel engine conditions. For constant volume and
      diesel engine (Volvo D12C) combustion modeling, this mechanism could be reduced
      to 88 species participating in 363 reactions.

PMID- 19409478
TI  - Clean conversion of cellulose into fermentable glucose.
AB  - We studied the process of conversion of microcrystalline-cellulose into
      fermentable glucose in the formic acid reaction system using cross
      polarization/magic angle spinning (13)C-nuclear magnetic resonance, X-ray
      diffraction and Fourier transform infrared spectroscopy. The results indicated
      that formic acid as an active agent was able to effectively penetrate into the
      interior space of the cellulose molecules, thus collapsing the rigid crystalline
      structure and allowing hydrolysis to occur easily in the amorphous zone as well
      as in the crystalline zone. The microcrystalline-cellulose was hydrolyzed using
      formic acid and 4% hydrochloric acid under mild conditions. The effects of
      hydrochloric acid concentration, the ratio of solid to liquid, temperature (55-75
      degrees C) and retention time (0-9 h), and the concentration of glucose were
      analyzed. The hydrolysis velocities of microcrystalline-cellulose were 6.14 x 10(
      3) h(-1) at 55 degrees C, 2.94 x 10(-2) h(-1) at 65 degrees C, and 6.84x10(-2) h(
      1) at 75 degrees C. The degradation velocities of glucose were 0.01 h(-1) at 55
      degrees C, 0.14 h(-1) at 65 degrees C, 0.34 h(-1) at 75 degrees C. The activation
      energy of microcrystalline-cellulose hydrolysis was 105.61 kJ/mol, and the
      activation energy of glucose degradation was 131.37 kJ/mol.

PMID- 19409479
TI  - Experimental study of the spray characteristics of biodiesel based on inedible
      oil.
AB  - We studied the spray characteristics of inedible oil using experimental and
      simulation methods. Spray penetration, spray cone angle and spray tip speed were
      measured at different biodiesel ratios in a constant volume vessel with wide
      visualization and high back pressure, using a high-speed camera. The
      characteristics of biodiesel spray were simulated under the same conditions using
      Star-CD software. The experimental results showed that, as the ratio of biodiesel
      in the blends increased, spray penetration and spray speed increased, but the
      spray cone angle decreased. Throughout the spray injection period, the region at
      0.05-0.475S (spray tip penetration) was a key area affecting spray cone angle.
      From 0.8 ms after injection, the spray penetration deviation ratios started to
      increase with increasing biodiesel blend ratios. Simulation results showed
      similar macroscopic spray characteristics to the experimental results for
      jatropha oil. The results also showed that the Sauter mean diameter of blend
      fuels was greater than that of diesel, and spray was more concentrated, due to
      the higher viscosity and surface tension of the biodiesel, compared with
      conventional diesel fuel. The macroscopic and microscopic spray properties of
      blended fuels containing 5%, 10% and 20% biodiesel were similar to diesel.

PMID- 19409480
TI  - Contrast features of CpG islands in the promoter and other regions in the dog
      genome.
AB  - The recent release of the domestic dog genome provides us with an ideal
      opportunity to investigate dog-specific genomic features. In this study, we
      performed a systematic analysis of CpG islands (CGIs), which are often considered
      gene markers, in the dog genome. Relative to the human and mouse genomes, the dog
      genome has a remarkably large number of CGIs and high CGI density, which is
      contributed by its noncoding sequences. Surprisingly, the dog genome has fewer
      CGIs associated with the promoter regions of genes than the human or the mouse.
      Further examination of functional features of dog-human-mouse homologous genes
      suggests that the dog might have undergone a faster erosion rate of promoter
      associated CGIs than the human or mouse. Some genetic or genomic factors such as
      local recombination rate and karyotype may be related to the unique dog CGI
      features.

PMID- 19409481
TI  - Does psychosocial stress predict symptomatic herpes simplex virus recurrence? A
      meta-analytic investigation on prospective studies.
AB  - Previous psychological studies have paid extensive attention to the association
      between psychosocial stress and symptomatic herpes simplex virus (HSV)
      recurrence, but subsequent research has been conducted and conflicting findings
      have been published. We aimed to quantify the longitudinal association between
      psychosocial stress and recurrent HSV in the contemporary literature. We searched
      Medline; PsycINFO; Web of Science; PubMed up to March 2009, and included
      prospective studies that investigated associations between psychosocial stress
      and symptomatic HSV recurrence. Two reviewers independently extracted data on
      study characteristics, quality, and estimates of associations. The overall meta
      analysis examining 11 articles (17 psychosocial and disease related
      relationships) exhibited a robust positive association between psychosocial
      stress and symptomatic HSV recurrence (correlation coefficient as combined effect
      size 0.083, 95% confidence interval 0.025-0.141, p=0.005). This finding was
      supported by more conservative analysis of aggregate effects and by sensitivity
      analysis of the methodologically strong studies. There were indications of
      publication bias in some analyses. Intriguingly, sensitivity analyses
      demonstrated that psychological distress was more strongly associated with
      symptomatic HSV recurrence than stress stimuli per se, and that psychosocial
      stress tended to be more strongly associated with oral than genital herpes
      recurrence. In conclusion, the current review reveals a robust relationship
      between psychosocial stress and symptomatic HSV recurrence, justifying further
      research in this field, especially clinical trials evaluating the efficacy of
      stress reduction interventions on HSV recurrence.

PMID- 19409482
TI  - Current developments in reproductive toxicity testing of pesticides.
AB  - A protocol to evaluate the potential developmental and reproductive effects of
      test chemicals has been developed by the Life Stages Task Force of the
      International Life Sciences Institute (ILSI)/Health and Environmental Sciences
      Institute (HESI) Agricultural Chemical Safety Assessment (ACSA) Technical
      Committee. Since the original publication, several international groups have
      provided public comment on conducting the test. The extended one-generation
      reproductive toxicity test is now under consideration as a potential test
      guideline. The protocol uses a flexible approach that is markedly different from
      the current multigenerational guidelines. It encourages the use of toxicokinetics
      when setting the doses, evaluates more than one rat per sex per litter in the F1
      offspring and does not necessarily require mating of the F1 to produce an F2 (F1
      mating may be triggered by the presence of effects in the P0 and developing F1
      rats). A number of additional reproductive endpoints, and the neurotoxicity and
      immunotoxicity cohorts are included. The ACSA protocol was developed with the
      goal of assuring that the methods are scientifically appropriate and the
      toxicological endpoints and exposure durations are relevant for risk assessment.
      Compared to existing testing strategies, the proposed approach uses substantially
      fewer animals, provides additional information on the neonate, juvenile and
      pubertal animal, and includes an estimation of human exposure potential for
      making decisions about the extent of testing required. In this paper, the
      evolution of the protocol since the 2006 publication is discussed. These changes
      reflect the collective input of a U.S. expert panel of government and industrial
      scientist convened in 2007 and discussions of an OECD expert group held in Paris,
      France (October, 2008).

PMID- 19409483
TI  - Receptor activator of nuclear factor-kappaB ligand-induced mouse osteoclast
      differentiation is associated with switching between NADPH oxidase homologues.
AB  - Reactive oxygen species (ROS) have been suggested to regulate receptor activator
      of nuclear factor-kappaB ligand (RANKL)-stimulated osteoclast differentiation.
      Stimulation of wild-type mouse bone marrow monocyte/macrophage lineage (BMM)
      cells by RANKL down-regulated NADPH oxidase 2 (Nox2) mRNA expression by half.
      RANKL reciprocally increased Nox1 mRNA levels and newly induced Nox4 transcript
      expression. BMM cells from Nox1 knockout (Nox1(-/-)) as well as Nox2(-/-) mice
      generated ROS in response to RANKL and differentiated into osteoclasts in the
      same way as wild-type BMM cells, which was assessed by the appearance of tartrate
      resistant acid phosphatase-positive, multinucleated cells having the ability to
      form resorption pits and by the expression of osteoclast marker genes. A small
      interfering RNA (siRNA) targeting Nox1 or Nox2 failed to inhibit the RANKL
      stimulated ROS generation and osteoclast formation in wild-type cells, whereas
      Nox1 and Nox2 siRNAs significantly suppressed the ROS generation and osteoclast
      formation in Nox2(-/-) and Nox1(-/-) cells, respectively. We also confirmed that
      Nox4 siRNA did not affect the RANKL-dependent events in Nox2(-/-) cells, whereas
      p22(phox) siRNA suppressed the events in both wild-type and Nox1(-/-) cells.
      Collectively, our results suggest that there may be a flexible compensatory
      mechanism between Nox1 and Nox2 for RANKL-stimulated ROS generation to facilitate
      osteoclast differentiation.

PMID- 19409484
TI  - Activation and inhibition of soluble guanylyl cyclase by S-nitrosocysteine:
      involvement of amino acid transport system L.
AB  - In this study the mechanism by which S-nitrosocysteine (CysNO) activates soluble
      guanylyl cyclase (sGC) has been investigated. CysNO is the S-nitrosated
      derivative of the amino acid cysteine and has previously been shown to be
      transported into various cell types by amino acid transport system L. Here we
      show, using both neuroblastoma and pulmonary artery smooth muscle cells, that
      CysNO stimulates cGMP formation at low concentrations, but this effect is lost at
      higher concentrations. Stimulation of cGMP accumulation occurs only after its
      transport into the cell and subsequent flavoprotein reductase-mediated metabolism
      to form nitric oxide (NO). Consequently, CysNO can be regarded as a cell-targeted
      NO-releasing agent. However, CysNO also functions as an NO-independent thiol
      modifying agent and can compromise cellular antioxidant defenses in a
      concentration-dependent manner. The observed biphasic nature of CysNO-dependent
      cGMP accumulation seems to be due to these two competing mechanisms. At higher
      concentrations, CysNO probably inactivates guanylyl cyclase through modification
      of an essential thiol group on the enzyme, either directly or as a result of a
      more generalized oxidative stress. We show here that higher concentrations of
      CysNO can increase cellular S-nitrosothiol content to nonphysiological levels,
      deplete cellular glutathione, and inhibit cGMP formation in parallel. Although
      the inhibition of sGC by S-nitrosation has been suggested as a mechanism of
      nitrovasodilator tolerance, in the case of CysNO, it seems to be more a
      reflection of a generalized oxidative stress placed upon the cell by the
      nonphysiological levels of intracellular S-nitrosothiol generated upon CysNO
      exposure.

PMID- 19409485
TI  - Nrf2 is involved in inhibiting Tat-induced HIV-1 long terminal repeat
      transactivation.
AB  - HIV-1 Tat is one of six regulatory proteins that are required for viral
      replication and is an attractive target for the development of new anti-HIV
      agents. The induction of oxidative stress, as shown with Tat, may have a bearing
      on the transactivation mechanism of transcription. The transcription factor Nrf2
      is a key player in the regulation of genes encoding many antioxidative response
      enzymes. Thus, the effect of Nrf2 on Tat-induced HIV-1 transcription was studied
      in MAGI cells. We found, for the first time, that Tat enhanced cellular
      expression of Nrf2 at the transcriptional and protein levels in these cells, and
      Tat activated antioxidant response element-driven gene expression. Tat
      simultaneously decreased the intracellular glutathione (GSH) levels and increased
      reactive oxygen species (ROS) production. The coordinated induction of ROS
      production, GSH depletion, and nuclear Nrf2 accumulation induced by Tat suggests
      that Nrf2 activation induced by Tat is not sufficient for protection against Tat
      induced oxidative stress. Furthermore, when cells were pretreated with scavengers
      of hydrogen peroxide such as N-acetylcysteine, or overexpression of Nrf2, or
      Keap1 knockdown by siRNA, Tat-induced HIV-1 LTR transactivation was suppressed,
      whereas buthionine sulfoximine or Nrf2 knockdown by siRNA potentiated Tat-induced
      HIV-1 LTR transactivation. Similar results were found in HIV-IIIB virus
      infection. Taken together, these data clearly show that Nrf2 inhibits Tat-induced
      HIV-1 LTR transactivation. This negative regulation of Tat-induced HIV-1 LTR
      transactivation by Nrf2 might be an important mechanism leading to its anti-HIV-1
      replicative activity.

PMID- 19409486
TI  - Long-term impact of an antioxidant-deficient neonatal diet on lipid and glucose
      metabolism.
AB  - Newborn infants are at risk for oxidative stress leading to metabolic syndrome
      features. Oxidative stress can be induced by oxidant load such as oxygen
      supplementation, peroxides from intravenous nutrition, or low antioxidant
      defenses. We hypothesize that a modulation of antioxidant defenses during the
      neonatal period, without external oxidant challenge, will have a long-term
      influence on energy metabolism. Guinea pigs were fed between their third and
      their seventh day of life a regular chow leading to "mature" antioxidant defenses
      or a deficient chow leading to lower antioxidant defenses. Between weeks 1 and
      14, the animals were fed regular chow. The hepatic oxidized redox status of
      glutathione associated with the deficient diet (-221 +/- 2 vs -228 +/- 1 mV, p <
      0.01) was maintained until 14 weeks. At 13-14 weeks, animals fed the deficient
      diet presented lower plasma TG (479 +/- 57 vs 853 +/- 32 microM, p < 0.01), lower
      blood glucose (5.8 +/- 0.3 vs 6.9 +/- 0.3 mM, p < 0.05), and better tolerance to
      glucose (p < 0.05). Blood glucose correlated negatively with the redox status (r2
      = 0.47, p < 0.01). Low antioxidant defenses during the neonatal period induce a
      better energy substrate profile associated with an oxidized redox status later in
      life. These findings suggest being aware of negative consequences when adopting
      "aggressive" antioxidant therapies in newborn infants.

PMID- 19409487
TI  - Role of IL-23 in mobilization of immunoregulatory nitric oxide- or superoxide
      producing Gr-1+ cells from bone marrow.
AB  - Spleens of mice injected with heat-killed Mycobacterium tuberculosis increase
      their Gr-1+ cell content and develop a system of interactive Ly-6G+ and Ly-6G-Gr
      1+ populations or "Greg" subsets, which, upon stimulation by activated T cells,
      produce immunoregulatory superoxide (O2(-)) and nitric oxide (NO), respectively.
      The balance between immunosuppressive NO and its antagonist O2(-) regulates T
      cell expansion, similar to regulation of vasodilation. Reduction of NO levels by
      O2(-) is required for efficient T cell expansion and development of autoimmunity.
      We studied the source of Gr-1+ cells in bone marrow (BM), where their levels were
      higher than in spleen, with both Greg subsets expressing strong activity. In the
      spleens of primed IL-23-/- mice, Ly-6G+ cells remained at naive levels and
      produced no O2(-). The complementary Ly-6G(-)Gr-1+ splenocytes and their
      suppressive activity were partially reduced. Surprisingly, Gr-1+ cell levels in
      BM of IL-23-/- mice were increased, as were their O2(-) and NO production.
      Transfer of primed BM cells partially restored regulatory function in the spleen
      of IL-23-/- recipients. The results suggest that IL-23 is involved in
      mobilization of O2(-)- and NO-producing Gr-1+ cells from BM, which may contribute
      to its widely studied role in (auto)immunity.

PMID- 19409488
TI  - Phenotypic variation in the Pseudomonas fluorescens clinical strain MFN1032.
AB  - Pseudomonas fluorescens is a highly heterogeneous species and includes both
      avirulent strains and clinical strains involved in nosocomial infections. We
      previously demonstrated that clinical strain MFN1032 has hemolytic activity
      involving phospholipase C (PlcC) and biosurfactants (BSs), similar to that of the
      opportunistic pathogen Pseudomonas aeruginosa. When incubated under specific
      conditions, MFN1032 forms translucent phenotypic variant colonies defective in
      hemolysis, but not necessarily in PlcC. We analyzed eight variants of the
      original strain MFN1032 and found that they clustered into two groups. Mutations
      of genes encoding the two-component regulatory system GacS/GacA are responsible
      for phenotypic variation in the first group of variants. These group 1 variants
      did not produce secondary metabolites and had impaired biofilm formation. The
      second group was composed of hyperflagellated cells with enhanced biofilm
      capacity: they did not produce BSs and were thus unable to swarm. Artificial
      reduction of the intracellular level of c-di-GMP restored the ability to form
      biofilm to levels shown by the wild type, but production of BSs was still
      repressed. Phenotypic variation might increase the virulence potential of this
      strain.

PMID- 19409489
TI  - A histidine kinase PmHHK1 regulates polar growth, sporulation and cell wall
      composition in the dimorphic fungus Penicillium marneffei.
AB  - Penicillium marneffei is an important opportunistic dimorphic fungal pathogen
      that can cause fatal systemic mycosis in AIDS patients. To find new ways of
      overcoming infection, candidate virulence associated genes and virulence
      mechanisms are under intensive investigation. In the present study, we have
      examined the function of a novel P. marneffei histidine kinase gene (PmHHK1)
      using dsRNAi mediated by Agrobacterium tumefaciens. Our results showed that
      reduction of PmHHK1 expression produces significant changes in morphogenesis
      (including polarized growth), sporulation and cell wall composition. Two
      component signaling systems are widespread in the eukaryotes outside the animal
      kingdom, and could be potential drug targets for antifungal chemotherapy.

PMID- 19409490
TI  - A BAC transgenic mouse model reveals neuron subtype-specific effects of a
      Generalized Epilepsy with Febrile Seizures Plus (GEFS+) mutation.
AB  - Mutations in the voltage-gated sodium channel SCN1A are responsible for a number
      of seizure disorders including Generalized Epilepsy with Febrile Seizures Plus
      (GEFS+) and Severe Myoclonic Epilepsy of Infancy (SMEI). To determine the effects
      of SCN1A mutations on channel function in vivo, we generated a bacterial
      artificial chromosome (BAC) transgenic mouse model that expresses the human SCN1A
      GEFS+ mutation, R1648H. Mice with the R1648H mutation exhibit a more severe
      response to the proconvulsant kainic acid compared with mice expressing a control
      Scn1a transgene. Electrophysiological analysis of dissociated neurons from mice
      with the R1648H mutation reveal delayed recovery from inactivation and increased
      use-dependent inactivation only in inhibitory bipolar neurons, as well as a
      hyperpolarizing shift in the voltage dependence of inactivation only in
      excitatory pyramidal neurons. These results demonstrate that the effects of SCN1A
      mutations are cell type-dependent and that the R1648H mutation specifically leads
      to a reduction in interneuron excitability.

PMID- 19409491
TI  - Ezetimibe decreases serum levels of asymmetric dimethylarginine (ADMA) and
      ameliorates renal injury in non-diabetic chronic kidney disease patients in a
      cholesterol-independent manner.
AB  - Synthesis of nitric oxide (NO) can be blocked by inhibition of nitric oxide
      synthase (NOS) active site with guanidino-substituted analogues of l-arginine
      such as asymmetric dimethylarginine (ADMA). There is growing evidence that
      elevation of serum ADMA levels play a role in the progression of atherosclerosis
      and chronic kidney disease (CKD) in high-risk patients. Further, dyslipidemia
      contributes to cardiorenal disease as well. However, effects of ezetimibe, a
      specific inhibitor of cholesterol absorption and widely used drug for the
      treatment of dyslipidemia, on serum ADMA levels and renal injury remain unknown.
      In this study, we examined whether ezetimibe treatment decreased serum levels of
      ADMA, proteinuria and urinary excretion levels of 8-hydroxydeoxyguanosine (8
      OHdG) and l-fatty acid binding protein (l-FABP), markers of oxidative stress and
      tubular injury, respectively and investigated their relationships in 10 non
      diabetic CKD patients with dyslipidemia. Ezetimibe treatment (10mg/day) for 6
      months significantly decreased circulating levels of LDL-cholesterol,
      triglycerides and ADMA, while it increased HDL-cholesterol levels. Further,
      ezetimibe treatment significantly reduced urinary excretion levels of protein, l
      FABP and 8-OHdG. In univariate analyses, serum ADMA levels were correlated with
      urinary protein, l-FABP and 8-OHdG levels. In multiple stepwise regression
      analysis, proteinuria was independently correlated with ADMA. Our present study
      demonstrated for the first time that ezetimibe decreased serum ADMA levels and
      improved renal injury in non-diabetic CKD patients with dyslipidemia in a
      cholesterol-independent manner. Ezetimibe may have pleiotropic actions, that is,
      ADMA-lowering and anti-oxidative effects, that could contribute to renoprotective
      properties of this lipid-lowering agent.

PMID- 19409494
TI  - Differential roles of Netrin-1 and its receptor DCC in inferior olivary neuron
      migration.
AB  - Netrin-1 was previously shown to be required for the tangential migration and
      survival of neurons that will form the inferior olivary nucleus (ION).
      Surprisingly, the compared analysis of mutant mice lacking either Netrin-1 or its
      major receptor DCC reveals striking phenotypic differences besides common
      features. Although ectopic stops of ION cell bodies occur in the same positions
      along the migratory stream in both mutants, the ION neurons' number is not
      affected by the lack of DCC whereas it is reduced in Netrin-1 mutant mice. Thus,
      cell death results from the absence of Netrin-1 and not from neuron mis-routing,
      arguing for a role of Netrin-1 as a survival factor in vivo. The secretion of
      Netrin-1 by the floor plate (FP) is strictly required - whereas DCC is not - to
      avoid ION axons' repulsion by the FP and allows them to cross it. Leading
      processes of neurons of other caudal precerebellar nuclei (PCN) cannot cross the
      FP in either mutant mouse, suggesting differential sensitivity or mechanism of
      action of Netrin-1 for leading processes of ION and other PCN neurons.

PMID- 19409493
TI  - Circumventricular organs: a novel site of neural stem cells in the adult brain.
AB  - Neurogenesis in the adult mammalian nervous system is now well established in the
      subventricular zone of the anterolateral ventricle and subgranular zone of the
      hippocampus. In these regions, neurons are thought to arise from neural stem
      cells, identified by their expression of specific intermediate filament proteins
      (nestin, vimentin, GFAP) and transcription factors (Sox2). In the present study,
      we show that in adult rat and mouse, the circumventricular organs (CVOs) are rich
      in nestin+, GFAP+, vimentin+ cells which express Sox2 and the cell cycle
      regulating protein Ki67. In culture, these cells proliferate as neurospheres and
      express neuronal (doublecortin+, beta-tubulin III+) and glial (S100beta+, GFAP+,
      RIP+) phenotypic traits. Further, our in vivo studies using bromodeoxyuridine
      show that CVO cells proliferate and undergo constitutive neurogenesis and
      gliogenesis. These findings suggest that CVOs may constitute a heretofore unknown
      source of stem/progenitor cells, capable of giving rise to new neurons and/or
      glia in the adult brain.

PMID- 19409495
TI  - Isolation of neural stem/progenitor cells by using EGF/FGF1 and FGF1B promoter
      driven green fluorescence from embryonic and adult mouse brains.
AB  - Fibroblast growth factor 1 (FGF1) and FGF2 have been shown to maintain the
      proliferation, self-renewal and multipotent capacities of neural stem/progenitor
      cells (NSPCs) in vitro. FGF1 is unique for binding to all known FGF receptors. In
      this study, we investigated if exogenous EGF and FGF1 could be used in the
      isolation of NSPCs from embryonic mouse brains. We demonstrated that EGF/FGF1
      responsive cells exhibited lower proliferation rate and neurosphere formation
      efficiency than EGF/FGF2-responsive NSPCs. However, EGF/FGF1-responsive mouse
      brain cells exhibited better neural differentiation capacities than EGF/FGF2
      responsive NSPCs at E11.5. Using F1BGFP reporter, we further demonstrated that
      F1BGFP+ cells showed similar multipotent capacities to CD133+ NSPCs, and could be
      induced more efficiently toward neuronal differentiation. Our results suggested
      that EGF/FGF1-responsive cells from E11.5 mouse brains could self-renew and have
      better multipotency than EGF/FGF2-responsive NSPCs. Further, CD133+ and F1BGFP+
      NSPCs may also represent different subsets of NSPCs during neural development and
      adult neurogenesis.

PMID- 19409492
TI  - Brain-derived neurotrophic factor regulates early postnatal developmental cell
      death of dopamine neurons of the substantia nigra in vivo.
AB  - Brain-derived neurotrophic factor (BDNF) was the first purified molecule
      identified to directly support the development of mesencephalic dopamine neurons.
      However, its physiologic role has remained unknown. Based on patterns of
      expression, it is unlikely to serve as a target-derived neurotrophic factor, but
      it may instead act locally in the mesencephalon, either released by afferent
      projections, or in autocrine fashion. To assess a possible local role, we blocked
      BDNF signaling in the substantia nigra (SN) of postnatal rats by injection of
      either neutralizing antibodies or a peptide antagonist. These treatments
      increased the magnitude of developmental cell death in the SN, indicating that
      endogenous local BDNF does play a regulatory role. However, we also find that
      elimination of BDNF in brain throughout postnatal development in
      BDNF(fl/fl):Nestin-Cre mice has no effect on the adult number of SN dopamine
      neurons. We postulate that other forms of trophic support may compensate for the
      elimination of BDNF during early development. Although the number of SN dopamine
      neurons is unchanged, their organization is disrupted. We conclude that BDNF
      plays a physiologic role in the postnatal development of SN dopamine neurons.

PMID- 19409496
TI  - Three-dimensional structure of Phyllomedusin, a NK1 receptor agonist bound to
      dodecylphosphocholine micelles.
AB  - Phyllomedusin, an amphibian tachykinin decapeptide, has been shown to be
      selective for Neurokinin 1 receptor. Because the micelle-associated structure may
      be relevant to the Phyllomedusin-receptor interaction, the three-dimensional
      structure of the Phyllomedusin in aqueous and micellar environments has been
      studied by two-dimensional proton nuclear magnetic resonance (2D (1)H NMR
      spectroscopy) and distance geometry calculations. Sequence specific resonance
      assignments of protons have been made from correlation spectroscopy (TOCSY, DQF
      COSY) and NOESY spectroscopy. The interproton distance constraints and dihedral
      angle constraints have been utilized to generate a family of structures using
      DYANA. The CD and NMR results show that, while in water Phyllomedusin prefers to
      be in an extended chain conformation, whereas in the presence of
      dodecylphosphocholine micelles, a membrane model system, a partial helical
      conformation is induced. Analysis of NMR data indicates that the global fold of
      Phyllomedusin can be explained in terms of equilibrium between 3(10)-helix and
      alpha-helix from residue 4 to 10. An extended highly flexible N-terminus displays
      some degree of order and a possible turn structure. A comparison between the
      conformational features of Phyllomedusin and different Neurokinin 1 receptor
      agonist indicates several common features in the distribution of hydrophobic and
      hydrophilic residues. The conformational similarities suggest that the molecules
      interact with receptor in an analogous manner.

PMID- 19409497
TI  - The impact of hunger on food cue processing: an event-related brain potential
      study.
AB  - The present study used event-related brain potentials to examine deprivation
      effects on visual attention to food stimuli at the level of distinct processing
      stages. Thirty-two healthy volunteers (16 females) were tested twice 1 week
      apart, either after 24 h of food deprivation or after normal food intake.
      Participants viewed a continuous stream of food and flower images while dense
      sensor ERPs were recorded. As revealed by distinct ERP modulations in relatively
      earlier and later time windows, deprivation affected the processing of food and
      flower pictures. Between 300 and 360 ms, food pictures were associated with
      enlarged occipito-temporal negativity and centro-parietal positivity in deprived
      compared to satiated state. Of main interest, in a later time window
      (approximately 450-600 ms), deprivation increased amplitudes of the late positive
      potential elicited by food pictures. Conversely, flower processing varied by
      motivational state with decreased positive potentials in the deprived state.
      Minimum-Norm analyses provided further evidence that deprivation enhanced visual
      attention to food cues in later processing stages. From the perspective of
      motivated attention, hunger may induce a heightened state of attention for food
      stimuli in a processing stage related to stimulus recognition and focused
      attention.

PMID- 19409499
TI  - Association between triallelic polymorphism of the serotonin transporter and
      [18F]MPPF binding potential at 5-HT1A receptors in healthy subjects.
AB  - Previous [(11)C]WAY100-635 PET studies have demonstrated that the short (S) and
      long (L) alleles of the serotonin transporter gene-linked polymorphic region (5
      HTTLPR) were associated with distinct patterns of 5-HT(1A) receptor distribution
      in human. However, these studies reported discordant findings and did not take
      into account the recent description of two functional variants of the L allele
      (L(A)/L(G)). To further explore this issue, we investigated the triallelic
      functional polymorphism of the 5-HTTLPR in 38 healthy volunteers who underwent a
      [(18)F]MPPF PET study of 5-HT1A receptors. We used a simplified reference tissue
      model to generate parametric images of [(18)F]MPPF binding potential (BP(ND)),
      and compared these data among the different genotypes using statistical
      parametric mapping and region of interest of the raphe nuclei. Homozygote
      carriers of the S allele demonstrated greater [(18)F]MPPF BP(ND) than carriers of
      the L(A) allele, but this association was only found in women. Differences in
      [(18)F]MPPF BP(ND) between women with and without L(A) allele were observed over
      large clusters encompassing the right and left temporal lobes, cingulate and
      perisylvian regions, as well as the right precuneus and frontal dorso-lateral
      cortex, and the left orbitofrontal cortex. In contrast, no difference was found
      between groups in the raphe nuclei. The greater [(18)F]MPPF BP(ND) observed in
      women homozygote carriers of the S allele could either reflect a greater 5-HT1A
      receptor density or a lower extracellular concentration of 5-HT. Our data suggest
      that any future PET studies of 5-HT1A receptors should incorporate the 5-HTTLPR
      polymorphism status of the population studied.

PMID- 19409498
TI  - Abnormalities of intrinsic functional connectivity in autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) impact social functioning and communication, and
      individuals with these disorders often have restrictive and repetitive behaviors.
      Accumulating data indicate that ASD is associated with alterations of neural
      circuitry. Functional MRI (FMRI) studies have focused on connectivity in the
      context of psychological tasks. However, even in the absence of a task, the brain
      exhibits a high degree of functional connectivity, known as intrinsic or resting
      connectivity. Notably, the default network, which includes the posterior
      cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial
      prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal
      gyrus, is strongly active when there is no task. Altered intrinsic connectivity
      within the default network may underlie offline processing that may actuate ASD
      impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the
      default network in ASD. Relative to controls, the ASD group showed weaker
      connectivity between the posterior cingulate cortex and superior frontal gyrus
      and stronger connectivity between the posterior cingulate cortex and both the
      right temporal lobe and right parahippocampal gyrus. Moreover, poorer social
      functioning in the ASD group was correlated with weaker connectivity between the
      posterior cingulate cortex and the superior frontal gyrus. In addition, more
      severe restricted and repetitive behaviors in ASD were correlated with stronger
      connectivity between the posterior cingulate cortex and right parahippocampal
      gyrus. These findings indicate that ASD subjects show altered intrinsic
      connectivity within the default network, and connectivity between these
      structures is associated with specific ASD symptoms.

PMID- 19409500
TI  - A longitudinal diffusion tensor imaging study on Wallerian degeneration of
      corticospinal tract after motor pathway stroke.
AB  - Wallerian degeneration of the corticospinal tract (CST) after motor pathway
      ischemic stroke can be characterized by diffusion tensor imaging (DTI). However,
      the dynamic evolution of the diffusion indices in the degenerated CST has not
      previously been completely identified. We investigated this dynamic evolution and
      the relationship between early changes of the diffusion indices in the
      degenerated CST and long-term clinical outcomes. DTI and neurological
      examinations were performed repeatedly in 9 patients with first-onset motor
      pathway subcortical infarction at 5 consecutive time points, i.e. within 1 week,
      at 2 weeks, 1 month, 3 months and 1 year. Using a region of interest method, we
      analyzed the ratios of the fractional anisotropy (rFA), mean diffusivity (rMD),
      primary eigenvalue (rlambda(1)) and transverse eigenvalue (rlambda(23)) between
      the affected and unaffected sides of the CSTs. We did not find any significant
      changes in the diffusion indices of the contralesional CSTs across time points.
      The rFA decreased monotonously during the first 3 months and then stabilized. The
      rMD increased after 2 weeks and stabilized after the third month. The rlambda(1)
      decreased during the first 2 weeks and then remained unchanged. The rlambda(23)
      increased during the first 3 months and then stabilized. We also found that the
      changes in the rFA between the first 2 time points were correlated with the NIHSS
      (P=0.00003) and the Motricity Indices (P=0.0004) after 1 year. Our results
      suggest that for patients with motor pathway stroke the diffusion indices in the
      degenerated CST stabilize within 3 months and that early changes in the rFA of
      the CST may predict long-term clinical outcomes.

PMID- 19409501
TI  - Aquaporin 4 correlates with apparent diffusion coefficient and hydrocephalus
      severity in the rat brain: a combined MRI-histological study.
AB  - Hydrocephalus features include ventricular dilatation and periventricular edema
      due to transependymal resorption of cerebrospinal fluid (CSF). Aquaporin 4
      (AQP4), a water channel protein located at the blood-brain barrier, might
      facilitate the removal of this excess of water from the parenchyma into the
      blood. First, we hypothesized a link between AQP4 expression and the severity of
      hydrocephalus. We further hypothesized that movements of water through AQP4 could
      affect apparent diffusion coefficient (ADC) measurements. Communicating
      inflammatory hydrocephalus was induced in 45 rats, and at various stages,
      magnetic resonance imaging (MRI) was used to measure CSF volume and
      periventricular ADC, with immunostaining being used to determine periventricular
      AQP4. We found an up-regulation of periventricular AQP4 in hydrocephalic rats
      that was strongly correlated with both CSF volume (Pearson=0.87, p<0.00001) and
      periventricular ADC (Pearson=0.85, p<0.00001). AQP4 were first located on
      astrocyte endfeet, but later on the whole membrane of astrocytes that became
      hypertrophic in the most severe and chronic hydrocephalic rats. These results
      show that AQP4 expression follows an adaptative profile to the severity of
      hydrocephalus, which is probably a protective response mechanism. They also
      suggest that ADC, on top of informing about cell sizes and interstitial bulk
      water, might also indirectly reflect quantitative water channel expression.

PMID- 19409502
TI  - Automatic segmentation of newborn brain MRI.
AB  - Quantitative brain tissue segmentation from newborn MRI offers the possibility of
      improved clinical decision making and diagnosis, new insight into the mechanisms
      of disease, and new methods for the evaluation of treatment protocols for preterm
      newborns. Such segmentation is challenging, however, due to the imaging
      characteristics of the developing brain. Existing techniques for newborn
      segmentation either achieve automation by ignoring critical distinctions between
      different tissue types or require extensive expert interaction. Because manual
      interaction is time consuming and introduces both bias and variability, we have
      developed a novel automatic segmentation algorithm for brain MRI of newborn
      infants. The key algorithmic contribution of this work is a new approach for
      automatically learning patient-specific class-conditional probability density
      functions. The algorithm achieves performance comparable to expert segmentations
      while automatically identifying cortical gray matter, subcortical gray matter,
      cerebrospinal fluid, myelinated white matter and unmyelinated white matter. We
      compared the performance of our algorithm with a previously published semi
      automated algorithm and with expert-drawn images. Our algorithm achieved an
      accuracy comparable with methods that require undesirable manual interaction.

PMID- 19409503
TI  - Nuclear transport factors in neuronal function.
AB  - Active nucleocytoplasmic transport of macromolecules requires soluble transport
      carriers of the importin/karyopherin superfamily. Although the nuclear transport
      machinery is essential in all eukaryotic cells, neurons must also mobilise
      importins and associated proteins to overcome unique spatiotemporal challenges.
      These include switches in importin alpha subtype expression during neuronal
      differentiation, localized axonal synthesis of importin beta1 to coordinate a
      retrograde injury signaling complex on axonal dynein, and trafficking of
      regulatory and signaling molecules from synaptic terminals to cell bodies.
      Targeting of RNAs encoding critical components of the importins complex and the
      Ran system to axons allows sophisticated local regulation of the system for
      mobilization upon need. Finally, a number of importin family members have been
      associated with mental or neurodegenerative diseases. The extended roles recently
      discovered for importins in the nervous system might also be relevant in non
      neuronal cells, and the localized modes of importin regulation in neurons offer
      new avenues to interrogate their cytoplasmic functions.

PMID- 19409504
TI  - Airway vascular reactivity and vascularisation in human chronic airway disease.
AB  - Altered bronchial vascular reactivity and remodelling including angiogenesis are
      documented features of asthma and other chronic inflammatory airway diseases.
      Expansion of the bronchial vasculature under these conditions involves both
      functional (vasodilation, hyperperfusion, increased microvascular permeability,
      oedema formation, and inflammatory cell recruitment) and structural changes
      (tissue and vascular remodelling) in the airways. These changes in airway
      vascular reactivity and vascularisation have significant pathophysiological
      consequences, which are manifest in the clinical symptoms of airway disease.
      Airway vascular reactivity is regulated by a wide variety of neurotransmitters
      and inflammatory mediators. Similarly, multiple growth factors are implicated in
      airway angiogenesis, with vascular endothelial growth factor amongst the most
      important. Increasing attention is focused on the complex interplay between
      angiogenic growth factors, airway smooth muscle and the various collagen-derived
      fragments that exhibit anti-angiogenic properties. The balance of these dynamic
      influences in airway neovascularisation processes and their therapeutic
      implications is just beginning to be elucidated. In this review article, we
      provide an account of recent developments in the areas of vascular reactivity and
      airway angiogenesis in chronic airway diseases.

PMID- 19409505
TI  - Stress and strain in the contractile and cytoskeletal filaments of airway smooth
      muscle.
AB  - Stress and strain are omnipresent in the lung due to constant lung volume
      fluctuation associated with respiration, and they modulate the phenotype and
      function of all cells residing in the airways including the airway smooth muscle
      (ASM) cell. There is ample evidence that the ASM cell is very sensitive to its
      physical environment, and can alter its structure and/or function accordingly,
      resulting in either desired or undesired consequences. The forces that are either
      conferred to the ASM cell due to external stretching or generated inside the cell
      must be borne and transmitted inside the cytoskeleton (CSK). Thus, maintaining
      appropriate levels of stress and strain within the CSK is essential for
      maintaining normal function. Despite the importance, the mechanisms
      regulating/dysregulating ASM cytoskeletal filaments in response to stress and
      strain remained poorly understood until only recently. For example, it is now
      understood that ASM length and force are dynamically regulated, and both can
      adapt over a wide range of length, rendering ASM one of the most malleable living
      tissues. The malleability reflects the CSK's dynamic mechanical properties and
      plasticity, both of which strongly interact with the loading on the CSK, and all
      together ultimately determines airway narrowing in pathology. Here we review the
      latest advances in our understanding of stress and strain in ASM cells, including
      the organization of contractile and cytoskeletal filaments, range and adaptation
      of functional length, structural and functional changes of the cell in response
      to mechanical perturbation, ASM tone as a mediator of strain-induced responses,
      and the novel glassy dynamic behaviors of the CSK in relation to asthma
      pathophysiology.

PMID- 19409506
TI  - Cloning and expression of StAR during gonadal cycle and hCG-induced oocyte
      maturation of air-breathing catfish, Clarias gariepinus.
AB  - Complementary DNAs encoding steroidogenic acute regulatory protein (StAR) have
      been isolated from different fish species, yet the relevance of StAR during
      gonadal cycle and more importantly in final oocyte maturation has not been
      assessed so far. A cDNA encoding StAR was isolated from the ovarian follicles of
      air-breathing catfish, Clarias gariepinus. Catfish StAR exhibited 55 to 72%
      identity at nucleotide level with other vertebrate orthologs. RT-PCR analysis of
      tissue distribution pattern demonstrated the presence of StAR mRNA in various
      tissues including gonads, kidney, liver, brain and intestine of catfish. Real
      time RT-PCR analysis revealed high expression of StAR mRNA in the pre-spawning
      phase of ovary while it was low in preparatory, spawning and regressed phases. In
      testis, maximum expression was noticed during the preparatory phase. During human
      chorionic gonadotropin (hCG)-induced oocyte maturation, both in vitro and in
      vivo, StAR mRNA levels were augmented by 2 h and then declined gradually to reach
      basal levels by 12 h as that of saline-treated controls. Taken together, high
      level of expression during hCG-induced oocyte maturation vis-a-vis in spawning
      suggests a role for StAR, in addition to the steroidogenic enzyme genes in final
      oocyte maturation.

PMID- 19409507
TI  - Biofilm formation in clinical Candida isolates and its association with
      virulence.
AB  - Biofilm formation, an important virulence trait of Candida species was measured
      in 107 Candida isolates from 32 candidemic patients by XTT [2,3-bis (2-methoxy
      4nitro-5-sulfo-phenyl)-2H-tetra-zolium-5-carboxanilide] activity and compared to
      biofilm formation of Candida isolates from oropharyngeal lesions of 19 AIDS
      patients. Biofilm formation by XTT varied among species and C. albicans; C.
      lusitaniae and C. krusei produced more biofilm than the other Candida species. C.
      tropicalis was the most dominant species isolated from blood followed by C.
      albicans, and other non-albicans species whereas only C. albicans was recovered
      from oral lesions. Importantly, though Biofilm formation was variable within a
      species it was stable in sequential isolates during chronic infection. Sequential
      isolates exhibited identical Karyotype pattern or RAPD patterns unless patients
      were co-infected with more than one strain. High biofilm formation was associated
      with slow growth rate but not with adherence. Murine infection studies
      demonstrated that, degree of in-vitro biofilm formation was associated with
      virulence in mice, as mice infected both with no and low biofilm formers survived
      longer than mice infected with high biofilm former C. albicans (p< or =0.001). We
      conclude that biofilm formation is a stable but strain specific characteristic
      that can greatly vary among C. albicans and non-albicans strains, and plays an
      important role in persistence of infection.

PMID- 19409508
TI  - Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum
      specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups
      living in Mali.
AB  - This study aimed to examine the effect of IL-4 -590 T/C polymorphism on the
      levels of malaria-specific IgE, IgG, IgG (1-4) subclasses as well as total IgE in
      the Fulani and their sympatric ethnic group, the Dogon, in Mali. Asymptomatic
      individuals, of the Fulani and the Dogon ethnic groups, were included in the
      study. IL-4 is involved in the regulation of IgE and IgG4 subclass. In line with
      this we found that within the Fulani, the T allele was associated with increased
      levels of total and anti-malarial IgE (P=0.02 and P=0.04, respectively). The
      Fulani T allele carriers had slightly higher levels of malarial specific IgG4 as
      compared to those with the CC genotype (P=0.08). No such differences were
      observed amongst the Dogon individuals. Taken together, these data indicate that
      the impact of IL-4 -590 variants on antibody levels may vary in different ethnic
      populations, and that this might affect the Ig-class and subclass distributions.

PMID- 19409509
TI  - The role of complement opsonization in interactions between F. tularensis subsp.
      novicida and human neutrophils.
AB  - The remarkable infectiousness of Francisella tularensis suggests that the
      bacterium efficiently evades innate immune responses that typically protect the
      host during its continuous exposure to environmental and commensal microbes. In
      our studies of the innate immune response to F. tularensis, we have observed
      that, unlike the live vaccine strain (LVS) of F. tularensis subsp. holarctica, F.
      tularensis subsp. novicida U112 opsonized in pooled human serum activated the
      NADPH oxidase when incubated with human neutrophils. Given previous observations
      that F. tularensis fixes relatively small quantities of complement component C3
      during incubation in human serum and the importance of C3 to neutrophil
      phagocytosis, we hypothesized that F. tularensis subsp. novicida may fix C3 in
      human serum more readily than would LVS. We now report that F. tularensis subsp.
      novicida fixed approximately six-fold more C3 than did LVS when incubated in 50%
      pooled human serum and that this complement opsonization was antibody-mediated.
      Furthermore, antibody-mediated C3 deposition enhanced bacterial uptake and was
      indispensable for the neutrophil oxidative response to F. tularensis subsp.
      novicida. Taken together, our results reveal important differences between these
      two strains of F. tularensis and may, in part, explain the low virulence of F.
      tularensis subsp. novicida for humans.

PMID- 19409510
TI  - Comparison of bioaccumulation of metals and induction of metallothioneins in two
      marine bivalves (Mytilus edulis and Mya arenaria).
AB  - The St. Lawrence maritime estuary (Quebec, Canada) is subjected to mixed inputs
      of pollutants and the study of the induction of metallothionein in species of
      economic and ecologic importance such as Mytilus edulis and Mya arenaria was
      pertinent to assess the consequences of pollution in this northern estuary.
      Bivalves from an area devoid of anthropogenic influences but characterized by
      background metal contamination (Franquelin) were actively transplanted within
      this location and in a site contaminated by urban, industrial and endogenous
      pollutants, Baie-Comeau (Baie-des-Anglais). Spatial differences in metal
      concentrations were shown between sites. Cu and Zn concentrations were higher in
      mussels from Baie-des-Anglais at the beginning of the transfer and after 1 and 2
      months. In clams, Zn concentrations were significantly higher in gills and
      digestive gland tissues for organisms transplanted in Baie-des-Anglais thus
      showing that spatio-temporal variations of metal concentrations were different
      between the two species studied. Mussels and clams partitioning of metals were
      shown to be different depending of the species, metal and/or tissue studied. In
      mussels, Cd and Cu concentrations decreased in both organs and both groups after
      the 3-month transfer in the polluted site. In mussels, total metal and
      metallothionein (MT) concentrations were positively correlated in digestive gland
      while in clams a positive correlation was only observed in gills.

PMID- 19409511
TI  - Limited global diversity of the Plasmodium vivax merozoite surface protein 4
      gene.
AB  - Merozoite surface proteins (MSPs) of the malaria parasites are major candidates
      for vaccine development targeting asexual blood stages. However, the diverse
      antigenic repertoire of these antigens that induce strain-specific protective
      immunity in human is a major challenge for vaccine design and often determines
      the efficacy of a vaccine. Here we further assessed the genetic diversity of
      Plasmodium vivax MSP4 (PvMSP4) protein using 195 parasite samples collected
      mostly from Thailand, Indonesia and Brazil. Overall, PvMSP4 is highly conserved
      with only eight amino acid substitutions. The majority of the haplotype diversity
      was restricted to the two short tetrapeptide repeat arrays in exon 1 and 2,
      respectively. Selection and neutrality tests indicated that exon 1 and the entire
      coding region of PvMSP4 were under purifying selection. Despite the limited
      nucleotide polymorphism of PvMSP4, significant genetic differentiation among the
      three major parasite populations was detected. Moreover, microgeographical
      heterogeneity was also evident in the parasite populations from different endemic
      areas of Thailand.

PMID- 19409512
TI  - Relaxation of purifying selection on the SAD lineage of live attenuated oral
      vaccines for rabies virus.
AB  - Analysis of patterns of nucleotide sequence diversity in wild-type rabies virus
      (RABV) genomes and in the SAD live attenuated oral vaccine lineage was used to
      test for the relaxation of purifying selection in the latter and provide evidence
      regarding the genomic regions where such relaxation of selection occurs. The wild
      type sequences showed evidence of strong past and ongoing purifying selection
      both on nonsynonymous sites in coding regions and on non-coding regions,
      particularly the start, end and 5' UTR regions. SAD vaccine sequences showed a
      relaxation of purifying selection at nonsynonymous sites in coding regions,
      resulting a substantial number of amino acid sequence polymorphisms at sites that
      were invariant in the wild-type sequences. Moreover, SAD vaccine sequences showed
      high levels of mutation accumulation in the non-coding regions that were most
      conserved in the wild-type sequences. Understanding the biological effects of the
      unique mutations accumulated in the vaccine lineage is important because of their
      potential effects on antigenicity and effectiveness of the vaccine.

PMID- 19409513
TI  - Conformational rearrangements upon Syk auto-phosphorylation.
AB  - Syk is a cytoplasmic tyrosine kinase that is activated after recruitment to
      immune receptors, triggering the phopshorylation of downstream targets. The
      kinase activity of Syk is controlled by an auto-inhibited conformation consisting
      of a regulatory region that contains two N-terminal Src homology 2 (SH2) domains
      inhibiting the catalytic activity of the kinase domain located at the C-terminus.
      The atomic structure of the related Zap-70 kinase and an electron microscopy (EM)
      model of Syk have revealed the structural mechanism of this auto-inhibition based
      on the formation of a compact conformation sustained by interactions between the
      regulatory and catalytic domains. On the other hand, the structural basis of Syk
      activation is not fully understood due to the lack of a 3D structure of full
      length Syk in an active conformation. Here, we have used single-particle electron
      microscopy to analyse the conformational changes taking place in an activated
      form of Syk induced by auto-phosphorylation. The conformation of phosphorylated
      Syk is reminiscent of the compact structure of the inhibited protein but
      significant conformational changes are observed in the regulatory region. These
      rearrangements could be sufficient to disrupt the inhibitory interactions,
      contributing to Syk activation. These results suggest that the regulation of the
      activation of Syk might be modulated by subtle changes in the positioning of the
      regulatory domains rather than a full opening mechanism as proposed for the Src
      kinases.

PMID- 19409514
TI  - Proteomic analysis of cells exposed to prefibrillar aggregates of HypF-N.
AB  - Several human diseases are associated with the deposition of stable ordered
      protein aggregates known as amyloid fibrils. In addition, a large wealth of data
      shows that proteins not involved in amyloidoses, are able to form, in vitro,
      amyloid-like prefibrillar and fibrillar assemblies indistinguishable from those
      grown from proteins associated with disease. Previous studies showed that early
      prefibrillar aggregates of the N-terminal domain of the prokaryotic hydrogenase
      maturation factor HypF (HypF-N) are cytotoxic, inducing early mitochondria
      membrane depolarization, activation of caspase 9 and eventually cell death. To
      gain knowledge on the molecular basis of HypF-N aggregate cytotoxicity, we
      performed a differential proteomic analysis of NIH-3T3 cells exposed to HypF-N
      prefibrillar aggregates in comparison with control cells. Two-dimensional gel
      electrophoresis followed by protein identification by MALDI-TOF MS, allowed us to
      identify 21 proteins differentially expressed. The changes of the expression
      level of proteins involved in stress response (Hsp60 and 78 kDa glucose-regulated
      protein) and in signal transduction (Focal adhesion kinase1) appear particularly
      interesting as possible determinants of the cell fate. The levels of some of the
      differently expressed proteins were modified also in similar studies carried out
      on cells exposed to Abeta or alpha-synuclein aggregates, supporting the existence
      of shared features of amyloid cytotoxicity.

PMID- 19409515
TI  - Cysteine cathepsins are not critical for TNF-alpha-induced cell death in T98G and
      U937 cells.
AB  - The tumor necrosis factor (TNF) is a cytokine known to be an important mediator
      of apoptosis and inflammation. It has been implicated in the pathogenesis of a
      number of diseases, including cancer and rheumatoid arthritis. TNF apoptosis has
      been known for a number of years to be critically dependent on caspases; however,
      recently it has been suggested that cysteine cathepsins might also be involved in
      the pathway. In the present work the hypothesis that cathepsins can act as an
      essential downstream mediator of TNF-alpha-triggered apoptosis was tested. The
      TNF-alpha apoptosis was investigated in two tumor-cell lines: U937 and T98G.
      Based on the use of pharmacological caspase inhibitors, the TNF-alpha induced
      caspase-dependent apoptotic cell death in both cell lines, which was accompanied
      by lysosomal destabilization and the release of cathepsins in the cytosol.
      However, blocking cysteine cathepsins with a broad-spectrum inhibitor, E64d, or a
      more specific cathepsin B inhibitor, CA-074Me, had no effect on the progression
      of the apoptosis in both cell lines, suggesting that the TNF-alpha apoptosis is
      not critically dependent on the cathepsins in these two cellular models.

PMID- 19409516
TI  - Effects of cross-linking and zero-link polymerization on oxygen transport and
      redox chemistry of bovine hemoglobin.
AB  - Cross-linked hemoglobins (Hbs) were found to have enhanced oxidative reactions
      which compromise the ability of cell-free Hb to carry oxygen. Zero-link bovine Hb
      (ZL-HbBv), also known as OxyVita, a large polymer held together by pseudopeptide
      bonds on the surface of adjacent tetramers, provides a model in which these
      reactions can be evaluated. The oxygen affinity of ZL-HbBv was greatly increased,
      whereas the oxygen binding cooperativity (n(50)) as well as the regulatory
      responses to pH and chloride ions was diminished. Rapid mixing kinetic studies
      revealed faster carbon monoxide (CO) and nitric oxide (NO) binding to ZL-HbBv,
      consistent with a more accessible heme pocket conformation. The rate of
      autoxidation of ferrous ZL-HbBv was 3 folds faster than the unmodified HbBv
      (control) but only slightly suppressed by the presence of superoxide dismutase
      and catalase enzymes. The peroxide (H(2)O(2)) reaction rates of ferric ZL-HbBv
      and its degradation were comparable to that of the control. The rate of heme loss
      from ZL-HbBv to a mutant apomyoglobin (H64Y/V68F) was also very close to that of
      the control. Taken together, allosteric and redox reactions of this protein are
      altered due to heme accessibility to solvent, however, the compact tetramer to
      tetramer interaction of the ZL-HbBv polymer appears to restrict heme loss even in
      the presence of excess H(2)O(2).

PMID- 19409517
TI  - Genetic selection for fast growth generates bone architecture characterised by
      enhanced periosteal expansion and limited consolidation of the cortices but a
      diminution in the early responses to mechanical loading.
AB  - Bone strength is, in part, dependent on a mechanical input that regulates the
      (re)modelling of skeletal elements to an appropriate size and architecture to
      resist fracture during habitual use. The rate of longitudinal bone growth in
      juveniles can also affect fracture incidence in adulthood, suggesting an
      influence of growth rate on later bone quality. We have compared the effects of
      fast and slow growth on bone strength and architecture in the tibiotarsi of
      embryonic and juvenile birds. The loading-related biochemical responses
      (intracellular G6PD activity and NO release) to mechanical load were also
      determined. Further, we have analysed the proliferation and differentiation
      characteristics of primary tibiotarsal osteoblasts from fast and slow-growing
      strains. We found that bones from chicks with divergent growth rates display
      equal resistance to applied loads, but weight-correction revealed that the bones
      from juvenile fast growth birds are weaker, with reduced stiffness and lower
      resistance to fracture. Primary osteoblasts from slow-growing juvenile birds
      proliferated more rapidly and had lower alkaline phosphatase activity. Bones from
      fast-growing embryonic chicks display rapid radial expansion and incomplete
      osteonal infilling but, importantly, lack mechanical responsiveness. These
      findings are further evidence that the ability to respond to mechanical inputs is
      crucial to adapt skeletal architecture to generate a functionally appropriate
      bone structure and that fast embryonic and juvenile growth rates may predispose
      bone to particular architectures with increased fragility in the adult.

PMID- 19409518
TI  - Trends in hip fracture epidemiology in Australia: possible impact of
      bisphosphonates and hormone replacement therapy.
AB  - The purposes of this study were to analyse trends in hip fracture (HF)
      epidemiology over a 13-year period (1994-2007) in the Australian Capital
      Territory (ACT), to assess the potential impact of concurrent changes in hormone
      replacement therapy (HRT) and bisphosphonate use and to present a new prediction
      of HFs in Australia up to 2021. Annual sex- and age-specific incidence rates (per
      100,000 population) were determined and standardized using the Australian 2006
      population. The projected number of HFs was estimated by two models applying age-
      and sex-specific HF rates averaged for 2002-2006 (model 1) or continuously
      changing as observed in this period (model 2, Poisson regression) to the
      projected population. In 2006 compared to 2001, the population > or = 60 years in
      the ACT increased by 19.7%. Over the last 5 years the average annual incidence HF
      rate compared to the previous 3-year period decreased in females > or = 60 years
      of age by 28.3%. Between 2001 and 2006 the number of prescriptions for HRT
      dispensed in the ACT declined by 54.6, while the number of prescriptions for
      bisphosphonate increased by 245%, accompanied by a decline in standardized
      incidence of HF rates of 36.4%, mainly in women (42.1%). This represents an
      annual cost for bisphosphonates per one prevented HF, of $A45,250 or $A576
      person/year. Compared to 2006 the total number of HFs in Australia according to
      model 1 will increase in 2011 by 20.1% and in 2021 by 58.8%, but according to
      model 2 will decrease by 15.5% in 2011 and 27.5% in 2021. Our data suggest that
      the previously predicted rising trend in HFs in elderly women reversed, but did
      not so for men. This was coincident with a significant fall in HRT use and
      increased prescribing of bisphosphonates, which is cost-effective. However
      caution should be used in attributing causation as this is an ecological study.
      If trends in HF observed in 2002-2006 continue, the absolute number of HFs in
      Australia in 2011-2021 will stabilise or decline (which is more likely), despite
      the rapid ageing of the population.

PMID- 19409519
TI  - Loss of the metalloprotease ADAM9 leads to cone-rod dystrophy in humans and
      retinal degeneration in mice.
AB  - Cone-rod dystrophy (CRD) is an inherited progressive retinal dystrophy affecting
      the function of cone and rod photoreceptors. By autozygosity mapping, we
      identified null mutations in the ADAM metallopeptidase domain 9 (ADAM9) gene in
      four consanguineous families with recessively inherited early-onset CRD. We also
      found reduced photoreceptor responses in Adam9 knockout mice, previously reported
      to be asymptomatic. In 12-month-old knockout mice, photoreceptors appear normal,
      but the apical processes of the retinal pigment epithelium (RPE) cells are
      disorganized and contact between photoreceptor outer segments (POSs) and the RPE
      apical surface is compromised. In 20-month-old mice, there is clear evidence of
      progressive retinal degeneration with disorganized POS and thinning of the outer
      nuclear layer (ONL) in addition to the anomaly at the POS-RPE junction. RPE basal
      deposits and macrophages were also apparent in older mice. These findings
      therefore not only identify ADAM9 as a CRD gene but also identify a form of
      pathology wherein retinal disease first manifests at the POS-RPE junction.

PMID- 19409520
TI  - Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder.
AB  - The MRE11/RAD50/NBN (MRN) complex plays a key role in recognizing and signaling
      DNA double-strand breaks (DSBs). Hypomorphic mutations in NBN (previously known
      as NBS1) and MRE11A give rise to the autosomal-recessive diseases Nijmegen
      breakage syndrome (NBS) and ataxia-telangiectasia-like disorder (ATLD),
      respectively. To date, no disease due to RAD50 deficiency has been described.
      Here, we report on a patient previously diagnosed as probably having NBS, with
      microcephaly, mental retardation, 'bird-like' face, and short stature. At
      variance with this diagnosis, she never had severe infections, had normal
      immunoglobulin levels, and did not develop lymphoid malignancy up to age 23
      years. We found that she is compound heterozygous for mutations in the RAD50 gene
      that give rise to low levels of unstable RAD50 protein. Cells from the patient
      were characterized by chromosomal instability; radiosensitivity; failure to form
      DNA damage-induced MRN foci; and impaired radiation-induced activation of and
      downstream signaling through the ATM protein, which is defective in the human
      genetic disorder ataxia-telangiectasia. These cells were also impaired in G1/S
      cell-cycle-checkpoint activation and displayed radioresistant DNA synthesis and
      G2-phase accumulation. The defective cellular phenotype was rescued by wild-type
      RAD50. In conclusion, we have identified and characterized a patient with a RAD50
      deficiency that results in a clinical phenotype that can be classified as an NBS
      like disorder (NBSLD).

PMID- 19409521
TI  - IFRD1 is a candidate gene for SMNA on chromosome 7q22-q23.
AB  - We have established strong linkage evidence that supports mapping autosomal
      dominant sensory/motor neuropathy with ataxia (SMNA) to chromosome 7q22-q32. SMNA
      is a rare neurological disorder whose phenotype encompasses both the central and
      the peripheral nervous system. In order to identify a gene responsible for SMNA,
      we have undertaken a comprehensive genomic evaluation of the region of linkage,
      including evaluation for repeat expansion and small deletions or duplications,
      capillary sequencing of candidate genes, and massively parallel sequencing of all
      coding exons. We excluded repeat expansion and small deletions or duplications as
      causative, and through microarray-based hybrid capture and massively parallel
      short-read sequencing, we identified a nonsynonymous variant in the human
      interferon-related developmental regulator gene 1 (IFRD1) as a disease-causing
      candidate. Sequence conservation, animal models, and protein structure evaluation
      support the involvement of IFRD1 in SMNA. Mutation analysis of IFRD1 in
      additional patients with similar phenotypes is needed for demonstration of
      causality and further evaluation of its importance in neurological diseases.

PMID- 19409522
TI  - The mitochondrial disulfide relay system protein GFER is mutated in autosomal
      recessive myopathy with cataract and combined respiratory-chain deficiency.
AB  - A disulfide relay system (DRS) was recently identified in the yeast mitochondrial
      intermembrane space (IMS) that consists of two essential components: the
      sulfhydryl oxidase Erv1 and the redox-regulated import receptor Mia40. The DRS
      drives the import of cysteine-rich proteins into the IMS via an oxidative folding
      mechanism. Erv1p is reoxidized within this system, transferring its electrons to
      molecular oxygen through interactions with cytochrome c and cytochrome c oxidase
      (COX), thereby linking the DRS to the respiratory chain. The role of the human
      Erv1 ortholog, GFER, in the DRS has been poorly explored. Using homozygosity
      mapping, we discovered that a mutation in the GFER gene causes an infantile
      mitochondrial disorder. Three children born to healthy consanguineous parents
      presented with progressive myopathy and partial combined respiratory-chain
      deficiency, congenital cataract, sensorineural hearing loss, and developmental
      delay. The consequences of the mutation at the level of the patient's muscle
      tissue and fibroblasts were 1) a reduction in complex I, II, and IV activity; 2)
      a lower cysteine-rich protein content; 3) abnormal ultrastructural morphology of
      the mitochondria, with enlargement of the IMS space; and 4) accelerated time
      dependent accumulation of multiple mtDNA deletions. Moreover, the Saccharomyces
      cerevisiae erv1(R182H) mutant strain reproduced the complex IV activity defect
      and exhibited genetic instability of the mtDNA and mitochondrial morphological
      defects. These findings shed light on the mechanisms of mitochondrial biogenesis,
      establish the role of GFER in the human DRS, and promote an understanding of the
      pathogenesis of a new mitochondrial disease.

PMID- 19409523
TI  - Multilocus Bayesian meta-analysis of gene-disease associations.
AB  - Meta-analysis is a vital tool in genetic epidemiology. However, meta-analyses to
      identify gene-disease associations are compromised when contributing studies have
      typed partially overlapping sets of markers. Currently, only marginal analyses
      are possible, and these are restricted to the subset of studies typing that
      marker. This does not allow full use of available data and leads to the
      confounding of marker effects by closely associated markers. We present a
      Bayesian approach that exploits prior information on underlying haplotypes to
      allow multi-marker analysis incorporating data from all relevant studies of a
      gene or region, irrespective of the markers typed. We present results from
      application of our approach to data on a possible association between PDE4D and
      ischemic stroke.

PMID- 19409524
TI  - Frontorhiny, a distinctive presentation of frontonasal dysplasia caused by
      recessive mutations in the ALX3 homeobox gene.
AB  - We describe a recessively inherited frontonasal malformation characterized by a
      distinctive facial appearance, with hypertelorism, wide nasal bridge, short nasal
      ridge, bifid nasal tip, broad columella, widely separated slit-like nares, long
      philtrum with prominent bilateral swellings, and midline notch in the upper lip
      and alveolus. Additional recurrent features present in a minority of individuals
      have been upper eyelid ptosis and midline dermoid cysts of craniofacial
      structures. Assuming recessive inheritance, we mapped the locus in three families
      to chromosome 1 and identified mutations in ALX3, which is located at band 1p13.3
      and encodes the aristaless-related ALX homeobox 3 transcription factor. In total,
      we identified seven different homozygous pathogenic mutations in seven families.
      These mutations comprise missense substitutions at critical positions within the
      conserved homeodomain as well as nonsense, frameshift, and splice-site mutations,
      all predicting severe or complete loss of function. Our findings contrast with
      previous studies of the orthologous murine gene, which showed no phenotype in
      Alx3(-/-) homozygotes, apparently as a result of functional redundancy with the
      paralogous Alx4 gene. We conclude that ALX3 is essential for normal facial
      development in humans and that deficiency causes a clinically recognizable
      phenotype, which we term frontorhiny.

PMID- 19409526
TI  - An evidence-based medicine review of lymphadenectomy extent for gastric cancer.

PMID- 19409527
TI  - Gallbladder ulcer eroding the cystic artery: a rare cause of hemobilia.
AB  - We report a hemorrhage from an eroded cystic artery in an ulcer of an inflamed
      calcolous gallbladder. Bleeding from the papilla was observed at side-view
      endoscopy. Echo endoscopy and contrast-enhanced computed tomography suggested a
      gallbladder bleeding. A clear-cut diagnosis was made by selective angiography,
      followed by embolization of the cystic artery, hence stopping the hemorrhage.
      Cystic artery bleeding into the gallbladder is rare. The diagnostic and
      therapeutic implications are discussed.

PMID- 19409528
TI  - Fibrin glue injection method with diluted thrombin for refractory postoperative
      digestive fistula.
AB  - BACKGROUND: The injection of the biological adhesive fibrin glue is often
      performed to treat postoperative digestive fistulas. However, it is not always
      effective especially in case of complex fistulas with large cavities, because the
      fibrin glue will coagulate before the mixed solutions fill the cavity, creating
      dead space. We report the results of fibrin glue injection with diluted thrombin
      solution. METHODS: We studied the tensile strength and coagulation time of the
      resulting fibrin glue at each dilution of the thrombin solution. Based on in
      vitro study, 18 patients who had developed postoperative digestive fistula were
      treated by fibrin glue injection with diluted thrombin solution. RESULTS: In
      vitro study proved that the dilution of thrombin prolonged the coagulation time
      of the fibrin glue to more than 1 minute with almost no change to the tensile
      strength of the glue until a certain dilution was reached. The fistulas of 16
      patients were successfully closed. CONCLUSIONS: Our simple method of fibrin glue
      injection is useful for refractory postoperative digestive fistula, even in cases
      of complex fistula with large cavities.

PMID- 19409530
TI  - WITHDRAWN: Erratum to "Tomato plants overexpressing CaKR1 enhanced tolerance to
      salt and oxidative stress" [Biochem. Biophys. Res. Commun. 363 (2007) 983-988].
AB  - This article has been withdrawn at the request of the author. 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- 19409529
TI  - Long-term follow-up results for ultrasound-guided vacuum-assisted removal of
      benign palpable breast mass.
AB  - BACKGROUND: This study was conducted to evaluate the long-term follow-up results
      from ultrasound-guided vacuum-assisted removal (US-VAR) of palpable benign breast
      mass and to identify patient characteristics that are correlated with recurrence
      or residual lesions. METHODS: US-VAR was performed on 95 benign, palpable breast
      masses that underwent subsequent intervention or at least a 2-year follow-up.
      During the follow-up period, we reviewed the lesion and patient's
      characteristics, and then determined whether the presence of recurrence or
      residual lesions was associated with any of the characteristics. RESULTS: Six
      lesions (6.3%) underwent subsequent intervention due to the recurrence of
      palpability. The remaining 89 lesions underwent imaging follow-up (range, 24 to
      60 months; mean, 35 months). Among these lesions, 32.6% (31 of 95 masses) showed
      sonographically visible, nonpalpable residual lesions. The remaining 61.1% (58
      masses) showed no evidence of residual lesion. The initial size of the lesion at
      VAR was the only characteristic correlated with recurrence (P = .017; odds ratio,
      1.238). CONCLUSION: Our long-term follow-up results show that US-VAR may be a
      useful alternative to surgical excision in the management of palpable breast
      masses.

PMID- 19409525
TI  - Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease,
      stroke, and Moyamoya disease, along with thoracic aortic disease.
AB  - The vascular smooth muscle cell (SMC)-specific isoform of alpha-actin (ACTA2) is
      a major component of the contractile apparatus in SMCs located throughout the
      arterial system. Heterozygous ACTA2 mutations cause familial thoracic aortic
      aneurysms and dissections (TAAD), but only half of mutation carriers have aortic
      disease. Linkage analysis and association studies of individuals in 20 families
      with ACTA2 mutations indicate that mutation carriers can have a diversity of
      vascular diseases, including premature onset of coronary artery disease (CAD) and
      premature ischemic strokes (including Moyamoya disease [MMD]), as well as
      previously defined TAAD. Sequencing of DNA from patients with nonfamilial TAAD
      and from premature-onset CAD patients independently identified ACTA2 mutations in
      these patients and premature onset strokes in family members with ACTA2
      mutations. Vascular pathology and analysis of explanted SMCs and myofibroblasts
      from patients harboring ACTA2 suggested that increased proliferation of SMCs
      contributed to occlusive diseases. These results indicate that heterozygous ACTA2
      mutations predispose patients to a variety of diffuse and diverse vascular
      diseases, including TAAD, premature CAD, ischemic strokes, and MMD. These data
      demonstrate that diffuse vascular diseases resulting from either occluded or
      enlarged arteries can be caused by mutations in a single gene and have direct
      implications for clinical management and research on familial vascular diseases.

PMID- 19409531
TI  - WITHDRAWN: Erratum to "Tomato plants overexpressing CaKR1 enhanced tolerance to
      salt and oxidative stress" [Biochem. Biophys. Res. Commun. 363 (2007) 983-988].
AB  - This article has been withdrawn at the request of the author. 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- 19409532
TI  - In vivo neuropathology of cortical changes in elderly persons with schizophrenia.
AB  - BACKGROUND: Elderly schizophrenia patients frequently develop cognitive
      impairment of unclear etiology. Magnetic resonance imaging (MRI) studies revealed
      brain structural abnormalities, but the pattern of cortical gray matter (GM)
      volume and its relationship with cognitive and behavioral symptoms are unknown.
      METHODS: Magnetic resonance scans were taken from elderly schizophrenia patients
      (n = 20, age 67 +/- 6 SD, Mini-Mental State Examination [MMSE] 23 +/- 4),
      Alzheimer's disease (AD) patients (n = 20, age 73 +/- 9, MMSE 22 +/- 4), and
      healthy elders (n = 20, age 73 +/- 8, MMSE 29 +/- 1). Patients were assessed with
      a comprehensive neuropsychological and behavioral battery. Cortical pattern
      matching and a region-of-interest analysis, based on Brodmann areas (BAs), were
      used to map three-dimensional (3-D) profiles of differences in patterns of gray
      matter volume among groups. RESULTS: Schizophrenia patients had 10% and 11% lower
      total left and right GM volume than healthy elders (p < .001) and 7% and 5% more
      than AD patients (p = .06 and ns). Regions that had both significantly less gray
      matter than control subjects and gray matter volume as low as AD mapped to the
      cingulate gyrus and orbitofrontal cortex (BA 30, 23, 24, 32, 25, 11). The
      strongest correlate of gray matter volume in elderly schizophrenia patients,
      although nonsignificant, was the positive symptom subscale of the Positive and
      Negative Syndrome Scale, mapping to the right anterior cingulate area (r = .42, p
      = .06). CONCLUSIONS: The orbitofrontal/cingulate region had low gray matter
      volume in elderly schizophrenia patients. Neither cognitive impairment nor
      psychiatric symptoms were significantly associated with structural differences,
      even if positive symptoms tended to be associated with increased gray matter
      volume in this area.

PMID- 19409533
TI  - Neural origins of human sickness in interoceptive responses to inflammation.
AB  - BACKGROUND: Inflammation is associated with psychological, emotional, and
      behavioral disturbance, known as sickness behavior. Inflammatory cytokines are
      implicated in coordinating this central motivational reorientation accompanying
      peripheral immunologic responses to pathogens. Studies in rodents suggest an
      afferent interoceptive neural mechanism, although comparable data in humans are
      lacking. METHODS: In a double-blind, randomized crossover study, 16 healthy male
      volunteers received typhoid vaccination or saline (placebo) injection in two
      experimental sessions. Profile of Mood State questionnaires were completed at
      baseline and at 2 and 3 hours. Two hours after injection, participants performed
      a high-demand color word Stroop task during functional magnetic resonance
      imaging. Blood samples were performed at baseline and immediately after scanning.
      RESULTS: Typhoid but not placebo injection produced a robust inflammatory
      response indexed by increased circulating interleukin-6 accompanied by a
      significant increase in fatigue, confusion, and impaired concentration at 3
      hours. Performance of the Stroop task under inflammation activated brain regions
      encoding representations of internal bodily state. Spatial and temporal
      characteristics of this response are consistent with interoceptive information
      flow via afferent autonomic fibers. During performance of this task, activity
      within interoceptive brain regions also predicted individual differences in
      inflammation-associated but not placebo-associated fatigue and confusion.
      Maintenance of cognitive performance, despite inflammation-associated fatigue,
      led to recruitment of additional prefrontal cortical regions. CONCLUSIONS: These
      findings suggest that peripheral infection selectively influences central nervous
      system function to generate core symptoms of sickness and reorient basic
      motivational states.

PMID- 19409534
TI  - Increased vulnerability to depressive-like behavior of mice with decreased
      expression of VGLUT1.
AB  - BACKGROUND: Many studies link depression to an increase in the excitatory
      inhibitory ratio in the forebrain. Presynaptic alterations in a shared pathway of
      the glutamate/gamma-aminobutyric acid (GABA) cycle may account for this
      imbalance. Evidence suggests that decreased vesicular glutamate transporter 1
      (VGLUT1) levels in the forebrain affect the glutamate/GABA cycle and induce
      helpless behavior. We studied decreased VGLUT1 as a potential factor enhancing a
      depressive-like phenotype in an animal model. METHODS: Glutamate and GABA
      synthesis as well as oxidative metabolism were studied in heterozygous mice for
      the VGLUT1+/- and wildtype. The regulation of neurotransmitter levels, proteins
      involved in the glutamate/GABA cycle, and behavior by both genotype and chronic
      mild stress (CMS) were studied. Finally, the effect of chronic imipramine on
      VGLUT1 control and CMS mice was studied. RESULTS: VGLUT1+/- mice showed increased
      neuronal synthesis of glutamate; decreased cortical and hippocampal GABA, VGLUT1,
      and excitatory amino acid transporter 1 (EAAT1) as well as helplessness and
      anhedonia. CMS induced an increase of glutamate and a decrease of GABA, the
      vesicular GABA transporter (VGAT), and glutamic acid decarboxylase 65 (GAD65) in
      both areas and led to upregulation of EAAT1 in the hippocampus. Moreover, CMS
      induced anhedonia, helplessness, anxiety, and impaired recognition memory.
      VGLUT1+/- CMS mice showed a combined phenotype (genotype plus stress) and
      specific alterations, such as an upregulation of VGLUT2 and hyperlocomotion.
      Moreover, an increased vulnerability to anhedonia and helplessness reversible by
      chronic imipramine was shown. CONCLUSIONS: These studies highlight a crucial role
      for decreased VGLUT1 in the forebrain as a biological mediator of increased
      vulnerability to chronic mild stress.

PMID- 19409537
TI  - Processing interactions between phonology and melody: vowels sing but consonants
      speak.
AB  - The aim of this study was to determine if two dimensions of song, the
      phonological part of lyrics and the melodic part of tunes, are processed in an
      independent or integrated way. In a series of five experiments, musically
      untrained participants classified bi-syllabic nonwords sung on two-tone melodic
      intervals. Their response had to be based on pitch contour, on nonword identity,
      or on the combination of pitch and nonword. When participants had to ignore
      irrelevant variations of the non-attended dimension, patterns of interference and
      facilitation allowed us to specify the processing interactions between
      dimensions. Results showed that consonants are processed more independently from
      melodic information than vowels are (Experiments 1-4). This difference between
      consonants and vowels was neither related to the sonority of the phoneme
      (Experiment 3), nor to the acoustical correlates between vowel quality and pitch
      height (Experiment 5). The implication of these results for our understanding of
      the functional relationships between musical and linguistic systems is discussed
      in light of the different evolutionary origins and linguistic functions of
      consonants and vowels.

PMID- 19409536
TI  - Structural investigation of a heteropolysaccharide isolated from the green fruits
      of Capsicum annuum.
AB  - A water-soluble polysaccharide isolated from the hot water extract of the green
      fruits of Capsicum annuum was found to consist of 3-O-acyl-L-rhamnose, D-methyl
      galacturonate, 6-O-methyl-D-galactose in a molar proportion of nearly 1:2:1.
      Structural investigation of the polysaccharide was carried out using total
      hydrolysis, methylation analysis, periodate oxidation followed by GLC-MS, and NMR
      experiments. On the basis of the above-mentioned experiments it is concluded that
      the following repeating unit is present in the polysaccharide.

PMID- 19409535
TI  - Total brain volume and corpus callosum size in medication-naive adolescents and
      young adults with autism spectrum disorder.
AB  - BACKGROUND: Increased total brain volume (TBV) has been reported for children
      with autism spectrum disorder (ASD) but studies in older ASD subjects have been
      contradictory. Similarly, studies of corpus callosum (CC) area in ASD differ with
      regard to inclusion criteria, age, and IQ. METHODS: In the present study, TBV,
      gray matter (GM), and white matter (WM) volume as well as midsagittal CC area
      were compared between 15 medication-naive, high-functioning adolescent and young
      adult ASD subjects and 15 healthy control individuals, and correlations with
      visuomotor coordination and imitation abilities were explored. In addition,
      computational surface-based methods were implemented to encode callosal thickness
      at high spatial resolution. RESULTS: Total brain volume, GM, and WM were
      increased and CC area was decreased in ASD subjects, a finding that was
      predominantly due to ASD subjects with lower IQ. Positive correlations of IQ with
      volume measures were observed only in control subjects. Autism spectrum disorder
      subjects showed reduced thickness in the posterior part of the CC. White matter
      volume showed a trend for negative correlation with dynamic balance and imitation
      abilities across groups. CONCLUSIONS: This study replicates previous structural
      magnetic resonance imaging (MRI) findings in ASD, emphasizes the role of IQ
      differences, and adds some evidence for functional implications of structural
      findings.

PMID- 19409538
TI  - Core knowledge and its limits: the domain of food.
AB  - Adults, preschool children, and nonhuman primates detect and categorize food
      objects according to substance information, conveyed primarily by color and
      texture. In contrast, they perceive and categorize artifacts primarily by shape
      and rigidity. The present experiments investigated the origins of this
      distinction. Using a looking time procedure, Experiment 1 extended previous
      findings that rhesus macaques (Macaca mulatta) generalize learning about novel
      food objects by color over changes in shape. Six additional experiments then
      investigated whether human infants show the same signature patterns of perception
      and generalization. Nine-month-old infants failed to detect food objects in
      accord with their intrinsic properties, in contrast to rhesus monkeys tested in
      previous research with identical displays. Eight-month-old infants did not
      privilege substance information over other features when categorizing foods, even
      though they detected and remembered this information. Moreover, infants showed
      the same property generalization patterns when presented with foods and tools.
      The category-specific patterns of perception and categorization shown by human
      adults, children, and adult monkeys therefore were not found in human infants,
      providing evidence for limits to infants' domains of knowledge.

PMID- 19409539
TI  - A Bayesian framework for word segmentation: exploring the effects of context.
AB  - Since the experiments of Saffran et al. [Saffran, J., Aslin, R., & Newport, E.
      (1996). Statistical learning in 8-month-old infants. Science, 274, 1926-1928],
      there has been a great deal of interest in the question of how statistical
      regularities in the speech stream might be used by infants to begin to identify
      individual words. In this work, we use computational modeling to explore the
      effects of different assumptions the learner might make regarding the nature of
      words--in particular, how these assumptions affect the kinds of words that are
      segmented from a corpus of transcribed child-directed speech. We develop several
      models within a Bayesian ideal observer framework, and use them to examine the
      consequences of assuming either that words are independent units, or units that
      help to predict other units. We show through empirical and theoretical results
      that the assumption of independence causes the learner to undersegment the
      corpus, with many two- and three-word sequences (e.g. what's that, do you, in the
      house) misidentified as individual words. In contrast, when the learner assumes
      that words are predictive, the resulting segmentation is far more accurate. These
      results indicate that taking context into account is important for a statistical
      word segmentation strategy to be successful, and raise the possibility that even
      young infants may be able to exploit more subtle statistical patterns than have
      usually been considered.

PMID- 19409540
TI  - Looking before you leap: a theory of motivated control of action.
AB  - The acquisition of volitional control depends, in part, on developing the ability
      to countermand a planned action. Many tasks have been used to tap the efficiency
      of this process, but few studies have investigated how it may be modulated by
      participants' motivation. Multiple mechanisms may be involved in the deliberate
      exercise of caution when incentives are provided. For example, control may
      involve modulation of the efficiency of the countermanding process, and/or
      inhibitory modulation of the impulse to go. One of the most commonly used
      paradigms to assess control of action is the Stop Signal Task, in which a primary
      Go stimulus is occasionally followed by a countermanding Stop signal, allowing a
      Stop Signal Reaction Time (SSRT) to be inferred as the outcome of a "horse race"
      between the go and countermanding processes. Here, we present a computational
      model in which high task motivation modulates proactive pre-stimulus inhibition
      of the go response. This allows responses to be calibrated so as to fall within a
      time-window that maximizes the probability of success, regardless of trial type,
      but does not decrease the observed SSRT. We report empirical support for the
      model from a sample of typically developing children, and discuss the broader
      implications for operationalizing measures of volitional control.

PMID- 19409541
TI  - Human frontal eye fields and target switching.
AB  - The frontal eye fields (FEF) have typically been predominantly investigated in
      terms of their role in the generation of eye movements. Lesions to this area,
      either accidental or experimental, disrupt saccades and electrical stimulation
      elicits eye movements. Recently there has been increasing interest in the
      involvement of this area in visual processes, including in tasks where eye
      movements were either not required or were precluded. In addition to being
      involved in a range of visual tasks, evidence from visual search paradigms has
      suggested that this area might be important when the defining quality of the
      target is unpredictable or that it may be involved in priming. We investigated
      the role of FEF in a task requiring localisation of a target defined by colour,
      in which the target colour was either maintained or switched across trials.
      Disruption of performance was seen on the task when transcranial magnetic
      stimulation (TMS) was delivered over the left FEF, specifically elevating
      response times on trials when the target and distracter colours were switched
      rather than affecting any benefit of repetition of the target attribute
      (priming). This result is consistent with altered modulation of extrastriate
      areas, consequently affecting the speed with which a switch of the target colour
      could be detected. This both offers an explanation for effects seen in
      unpredictable feature search and is consistent with other TMS and
      microstimulation studies showing that FEF modulates responses of extrastriate
      cortex.

PMID- 19409542
TI  - New section: Cortex Clinical Neuroanatomy.

PMID- 19409543
TI  - Ovarian reserve in women who remain premenopausal after chemotherapy for early
      stage breast cancer.
AB  - OBJECTIVE: To compare markers of ovarian reserve between women exposed to
      cytotoxic chemotherapy for early stage breast cancer and matched controls.
      DESIGN: Cross-sectional evaluation of markers of ovarian reserve. SETTING: Dana
      Farber/Brigham and Women's Cancer Center, Massachusetts General Hospital, and
      Faulkner Hospital in Boston, MA. PATIENT(S): Breast cancer survivors with
      continued menses after chemotherapy were compared with age-matched, gravidity
      matched controls. MAIN OUTCOME MEASURE(S): Antral follicle count (AFC), anti
      Mullerian hormone (AMH), FSH, inhibin B (InB), and E(2) on day 2, 3, or 4 of the
      menstrual cycle. A Bonferroni correction was performed to correct for multiple
      comparisons. RESULT(S): Twenty survivors and 20 controls were evaluated; 50% of
      survivors were currently on tamoxifen. Median AFC was 6 for survivors and 9.5 for
      controls. There were significant differences between the two groups in AFC, AMH,
      and nonsignificant differences in FSH and InB, all indicating better ovarian
      reserve in controls. The AFC and AMH levels were highly correlated (r = 0.72).
      Survivors on tamoxifen had lower AFC, AMH, InB, and higher E(2) than nontamoxifen
      treated survivors. CONCLUSION(S): Premenopausal breast cancer survivors have
      diminished ovarian reserve compared with controls.

PMID- 19409544
TI  - A prospective, randomized trial on the effect of atmospheric versus reduced
      oxygen concentration on the outcome of intracytoplasmic sperm injection cycles.
AB  - OBJECTIVE: To assess whether the embryo cultivation at different oxygen tensions
      had any effect on intracytoplasmic sperm injection (ICSI) outcome. DESIGN:
      Prospective randomized trial. SETTING: University clinical center. PATIENT(S):
      Women undergoing ICSI (n = 647). INTERVENTION(S): Culturing of embryos, either at
      6% CO(2), 5% O(2), 89% N(2), or at 6% CO(2) in air. MAIN OUTCOME MEASURE(S): The
      primary outcome was ongoing pregnancy rates (PR). SECONDARY OUTCOMES: cumulative
      PRs, implantation, and embryo quality, for both treatment groups and clinical
      outcomes for subgroups (optimal cycles, poor responders, older women). RESULT(S):
      Although low oxygen resulted in a higher proportion of good day 2 embryos (0.547
      +/- 0.021 vs. 0.39 +/- 0.019) and optimal blastocysts (0.162 +/- 0.199 vs. 0.083
      +/- 0.128), the ongoing PRs (31.6% vs. 27.1%) and implantation rates (28.8% vs.
      25.2%) were similar in both oxygen groups. Low oxygen caused a higher cumulative
      PR (38% vs. 28.3%) in the main group and a higher PR in the poor responder
      subgroup (23% vs. 9.8%) with embryo transfers performed mostly on day 3.
      CONCLUSION(S): The use of reduced oxygen in IVF is reasonable, irrespective of
      the duration of embryo culture. It improves embryo development and cumulative PR
      and is also recommended in poor responding cycles.

PMID- 19409545
TI  - Multistep and single-step treatment of human spermatozoa with cryoprotectants.
AB  - OBJECTIVE: To compare the impact of multi- and single-step addition of
      cryoprotectants on human spermatozoa. DESIGN: Human semen was subjected to
      cryoprotective agents (CPAs) in both one-step and multistep protocols before
      removal of the CPAs by multi-step and single-step methods. SETTING: Infertility
      clinic. PATIENT(S): Healthy normozoospermic volunteers. INTERVENTION(S): Single-
      and multistep addition and removal of a range of CPAs. MAIN OUTCOME MEASURE(S):
      Analysis of tail morphology and total and progressive motility, as well as
      kinematic parameters, in medium and sperm penetration into artificial mucus.
      RESULT(S): While no CPA drastically affected sperm vitality, some were more
      deleterious than others. Propane-1,3-diol was the least damaging to sperm
      function, whereas glycerol and ethyl(hydroxymethyl)propane were particularly
      disruptive. For all CPAs, multistep addition and removal of CPAs proved less
      damaging to sperm function than the single-step protocol. CONCLUSION(S): Optimal
      CPAs may be those that minimize osmotic stresses to spermatozoa during prefreeze
      and post-thaw procedures.

PMID- 19409546
TI  - Transvaginal ultrasound-guided ovarian interstitial laser treatment in
      anovulatory women with polycystic ovary syndrome: a randomized clinical trial on
      the effect of laser dose used on the outcome.
AB  - OBJECTIVE: To explore an optimal laser dose of transvaginal ultrasound-guided
      ovarian interstitial laser coagulation in management of anovulation in patients
      with polycystic ovary syndrome (PCOS). DESIGN: Randomized, controlled trial.
      SETTING: A reproductive medical center. PATIENT(S): Eighty women with PCOS and
      clomiphene citrate-resistant infertility underwent ultrasound-guided transvaginal
      ovarian interstitial yttrium aluminum garnet laser treatment. All subjects were
      divided randomly into four groups of A, B, C, and D. INTERVENTION(S): Group A,
      one coagulation point per ovary; group B, two points; group C, three points;
      group D, four to five points. MAIN OUTCOME MEASURE(S): Postoperative ovulation
      rate, pregnancy rate, and some biochemical parameters. RESULT(S): The rates of
      ovulation in groups C (75.00%, 95% confidence interval [CI]: 51%-91%) and D
      (80.00%, 95% CI: 56%-94%) within 6 postoperative months were significantly higher
      than in groups A (5.00%, 95% CI: 0%-25%) and B (15.00%, 95% CI: 3%-38%). The
      pregnancy rates in groups C (45.00%, 95% CI: 23%-69%) and D (40.00%, 95% CI: 19%
      64%) also were significantly higher than in groups A (5.00%, 95% CI: 0-25%) and B
      (10.00%, 95% CI: 1%-32%). The mean serum T levels were significantly lower in
      groups C (2.08 +/- 0.62 nmol/L) and D (2.07 +/- 0.42 nmol/L) compared with groups
      A (3.10 +/- 0.63 nmol/L) and B (2.95 +/- 0.63 nmol/L). CONCLUSION(S): One and two
      intraovarian laser coagulation points per ovary are associated with poor
      outcomes. Three points per ovary seem to represent the plateau of effective dose
      for the ovarian interstitial laser treatment in PCOS.

PMID- 19409547
TI  - Assay reproducibility and within-person variation of Mullerian inhibiting
      substance.
AB  - OBJECTIVES: To assess reproducibility of a commercial mullerian inhibiting
      substance (MIS) assay and evaluate within-person variation in serum MIS levels.
      DESIGN: Assay reproducibility was evaluated by measuring MIS in multiple serum
      aliquots from the same blood collection. Within-person variation was assessed by
      measuring MIS in serum collected twice from the same individuals. SETTING: Cancer
      Prevention Biomarker and Genotyping Facility, fox Chase Cancer Center,
      Philadelphia, Pennsylvania. PATIENT(S): Assay reproducibility was evaluated using
      serum from five volunteers with regular menstrual cycles. Within-person variation
      was evaluated in serum from 20 premenopausal women who donated blood twice at
      least 1 year apart. INTERVENTION(S): For both studies, samples were randomly
      ordered in batches and laboratory personnel were blinded to which aliquots were
      from the same subject. MAIN OUTCOME MEASURE(S): The MIS was measured by ELISA.
      RESULT(S): Within- and between-batch coefficients of variation (CVs) of the assay
      were 7.9% and 12.3%, respectively. After deleting one subject with extreme
      values, these CVs decreased to 7.6% and 7.7%, respectively. Within- and between
      subject variance in MIS measurements were 2.19 and 0.31, respectively, and the
      intraclass correlation coefficient was 0.88 (95% confidence interval .77-.98).
      CONCLUSION(S): The MIS serum concentration is relatively stable over 1 year in
      premenopausal women and can be measured with good reproducibility using a
      commercial kit.

PMID- 19409548
TI  - Clinical predictors of human blastocyst formation and pregnancy after extended
      embryo culture and transfer.
AB  - OBJECTIVE: To determine the clinical factors associated with blastocyst
      development and pregnancy. DESIGN: Evaluation of a prospectively collected IVF
      database. SETTING: An academic IVF practice. PATIENT(S): Couples (n = 529)
      undergoing their first IVF cycle who qualified for extended embryo culture (more
      than six zygotes) over the past 5 years. INTERVENTION(S): Seven or eight zygotes
      were cultured for 5 days, assessed for quality, and then transferred with excess
      zygotes cryopreserved at the pronuclear stage. MAIN OUTCOME MEASURE(S): Clinical
      predictors of blastocyst development and pregnancy. RESULT(S): The mean
      blastocyst development rate was 49.8%, with a median number of total and good
      quality blastocysts of 4 and 2, respectively. Clinical factors that were
      significantly associated with good-quality blastocyst formation were younger
      female age, increased parity, standard insemination, and lower doses of
      gonadotropins. Clinical factors that were significantly associated with
      successful pregnancy were younger female age, higher antral follicle counts,
      greater numbers of total and good-/excellent-quality blastocysts, and absence of
      male factor infertility. CONCLUSION(S): Several clinical factors are associated
      with the development of good-quality blastocysts after extended embryo culture
      and successful pregnancy outcome. These patient and cycle characteristics may be
      very useful in selecting the best candidates for extended embryo culture and
      single blastocyst transfers, thus optimizing outcomes while reducing the risks
      associated with multiple pregnancies.

PMID- 19409549
TI  - Hysteroscopic tubal sterilization: a systematic review of the Essure system.
AB  - OBJECTIVE: To update the evidence of the efficacy and safety of the Essure
      system. Female sterilization has undergone changes in the last decade. Besides
      laparoscopic tubal occlusion, the Essure system is now a viable option, with
      about 200,000 women sterilized using this method. DESIGN: The review is based on
      the report of the Alberta Heritage Foundation for Medical Research and completed
      with systematic literature searches up to April 8, 2008. SETTING: The Managed
      Uptake of Medical Methods program of the Finnish National Research and
      Development Center for Health and Welfare. PATIENT(S): Women over 30 years, who
      had been sterilized by the Essure method. INTERVENTION(S): Hysteroscopic tubal
      sterilization using Essure system. MAIN OUTCOME MEASURE(S):
      Efficacy/effectiveness, adverse events, costs. RESULT(S): Sterilization by Essure
      can be performed under local anesthesia or with oral analgesics in ambulatory
      settings. However, sterilization is not immediate and women must use additional
      contraception for 3 months until permanent tubal occlusion is verified by
      transvaginal ultrasound, hysterosalpingosonography, hysterosalpingography, or
      pelvic radiography. The evidence on efficacy and safety is mainly available from
      short follow-up case series but shows good efficacy and safety of the Essure
      system. Only a few small risks are associated with the procedure. Two economic
      studies, one of which implemented Essure as an in-office procedure, suggest that
      Essure could be more cost-effective than laparoscopic sterilization, but more
      information on the total cost is needed. CONCLUSION(S): The Essure system appears
      to be safe, permanent, irreversible, and a less invasive method of contraception
      compared with laparoscopic sterilization.

PMID- 19409550
TI  - Technology requirements for preimplantation genetic diagnosis to improve assisted
      reproduction outcomes.
AB  - Preimplantation genetic diagnosis has been proposed as a method to improve
      assisted reproduction technology outcomes, but different techniques have produced
      conflicting results. The use of appropriate techniques may provide positive
      outcomes.

PMID- 19409551
TI  - Immunization with a DNA vaccine of testis-specific sodium-hydrogen exchanger by
      oral feeding or nasal instillation reduces fertility in female mice.
AB  - OBJECTIVE: To investigate the effect of immunization with a DNA vaccine of testis
      specific sodium-hydrogen exchanger (tsNHE) via oral feeding or nasal instillation
      on fertility in female mice and to look at its potential mechanism. DESIGN:
      Prospective, research study. SETTING: Institution-affiliated research laboratory.
      ANIMAL(S): Sexual mature BALB/c mice. INTERVENTION(S): Female mice immunized
      orally or nasally with the DNA vaccine at 2-week' intervals. MAIN OUTCOME
      MEASURE(S): Number of newborns and fertility rate of the vaccinated female mice
      were scored. RESULT(S): We identified a novel testis-specific sodium-hydrogen
      exchanger, tsNHE, which is localized to the principal piece of sperm flagellum.
      Immunization of female mice with the tsNHE DNA vaccine via oral feeding or nasal
      instillation statistically significantly decreased fertility rate and the newborn
      numbers compared with the controls. The antiserum or vaginal fluid from the tsNHE
      cDNA vaccinated female mice could specifically recognize the principal piece of
      sperm tail and triggered sperm agglutination. The antibodies also showed a
      statistically significant inhibitory effect on in vitro sperm motility and
      fertilization. CONCLUSION(S): The sodium-hydrogen exchanger might be an excellent
      target molecule for developing a new contraceptive.

PMID- 19409552
TI  - Histopathologic features of endometriotic rectal nodules and the implications for
      management by rectal nodule excision.
AB  - Using data from 27 women with deep rectal endometriosis, managed by segmental
      resection, we observed that in 89% of cases active glandular endometrial foci
      were responsible for a deeper infiltration of rectal layers than that of fibrosis
      and smooth fibers by 5 mm on average. These data might be useful for surgeons
      performing rectal nodule excision, suggesting the benefits of administrating
      postoperative medical treatment to reduce the risk of rectal recurrences caused
      by remaining active endometriotic foci.

PMID- 19409553
TI  - The impact of peritoneal fluid from healthy women and from women with
      endometriosis on sperm DNA and its relationship to the sperm deformity index.
AB  - OBJECTIVE: To study the effect of peritoneal fluid (PF) from healthy women and
      from women with endometriosis on sperm DNA and its relationship to sperm
      morphology as assessed by the sperm deformity index (SDI). DESIGN: Experimental
      study. SETTING: Research laboratory at an academic hospital. PATIENT(S): Healthy
      women undergoing laparoscopic tubal ligation and women with endometriosis.
      INTERVENTION(S): Aliquots of prepared sperm from 10 healthy donors were incubated
      with PF from healthy women undergoing laparoscopic tubal ligation (treatment 1, n
      = 10), with PF from patients with endometriosis (treatment 2, n = 10), and with
      human tubal fluid media with 10% bovine serum albumin (control, n = 10). MAIN
      OUTCOME MEASURE(S): Sperm DNA fragmentation was assessed by terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and SDI.
      RESULT(S): There was a significant increase in sperm DNA damage at 24 hours
      compared with at 1.5 and 3 hours. The SDI scores significantly correlated with
      sperm DNA damage after 1.5 and 24 hours of incubation in all aliquots. Percentage
      normal morphology did not correlate with DNA damage. CONCLUSION(S): In vitro
      exposure of sperm to PF from patients with endometriosis is associated with
      significantly increased DNA damage. There is evidence of interdependence between
      the sperm morphology as assessed by SDI scores and DNA damage. The significant
      increase in sperm DNA damage observed after 24 hours of incubation may be
      clinically relevant.

PMID- 19409554
TI  - The effect of oral micronized progesterone on hormonal and metabolic parameters
      in anovulatory patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the effects of oral natural micronized P on hormonal
      and metabolic parameters in patients with polycystic ovary syndrome (PCOS) and to
      answer the clinical question whether induction of withdrawal bleeding is a
      necessity for the comparison of hormonal and metabolic data in subjects with
      PCOS. DESIGN: Prospective clinical study. SETTING: Academic medical center.
      PATIENT(S): Twenty-eight reproductive-aged women with PCOS. MAIN OUTCOME
      MEASURE(S): Blood sampling was collected at baseline, after 7 days of oral
      natural micronized P (200 mg) administration, and after withdrawal bleeding. At
      these three stages hormonal parameters and homeostasis assessment model (HOMA-IR)
      index were assessed in all patients. RESULT(S): Oral natural micronized P
      administration did not alter significantly insulin sensitivity index and androgen
      levels; however, LH was decreased when postbleeding values were compared to
      baseline. Nevertheless, after oral natural micronized P administration, P and
      17alpha-hydroxyprogesterone (17-OHP) concentrations were increased, and HOMA-IR
      was decreased, whereas androgens levels were not altered, in comparison with
      baseline. CONCLUSION(S): The induction of withdrawal bleeding, with this regimen,
      does not appear to be a necessity for the assessment of hormonal and metabolic
      profile in anovulatory women with PCOS.

PMID- 19409555
TI  - Vascular endothelial growth factor A and its two receptors in human preantral
      follicles from fetuses, girls, and women.
AB  - OBJECTIVE: To investigate the expression of vascular endothelial growth factor A
      (VEGF-A) and that its two receptors (VEGFR1, VEGFR2) in human preantral
      follicles. DESIGN: Immunohistochemical, in situ hybridization, and reverse
      transcriptase polymerase chain reaction (RT-PCR) study of the expression of the
      VEGF-A system in human ovaries. SETTING: Major tertiary-care academic center.
      PATIENT(S): Twenty-two patients who underwent pregnancy terminations at 21-35
      gestational weeks and 29 girls/women aged 5-39 years who underwent ovarian
      laparoscopies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Laboratory
      analysis of human ovarian specimens. RESULT(S): Immunhistochemistry and in situ
      hybridization revealed the expression of the proteins and mRNA transcripts for
      VEGFR1 and VEGFR2 in oocytes, granulosa cells, and stroma cells from fetuses and
      girls/women. The protein for VEGF-A was detected immunohistochemically in
      oocytes, granulosa cells, and stroma cells from fetuses and girls. VEGF-A and
      VEGFR1 proteins were expressed more strongly than VEGFR2. VEGF-A(121), VEGF
      A(165), and VEGF-A(189) isoforms were identified by RT-PCR in the ovarian samples
      from fetuses and women. CONCLUSION(S): The presence of the VEGF-A receptors,
      particularly in the granulosa cells, suggests that VEGF-A might be involved in
      proliferation initiation of primordial follicles or play an as yet unknown role
      in human preantral follicles.

PMID- 19409556
TI  - Monozygotic twinning: an eight-year experience at a large IVF center.
AB  - OBJECTIVE: To characterize incidence, chorionicity, amnionicity, and pregnancy
      outcome for monozygotic twin pregnancy (MZT) after IVF. DESIGN: Retrospective
      review. SETTING: University-based fertility center. PATIENT(S): Autologous and
      oocyte donation IVF cycles eventuating in 4,976 clinical gestations from 2000 to
      2007. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): MZT incidence,
      chorionicity, zygosity, pregnancy outcome. RESULT(S): Ninety-eight MZTs were
      diagnosed after first-trimester ultrasound evaluation (2% incidence). The
      incidence in cycles transfering autologous oocytes was 1.7% but was 3.3% with
      donor oocytes; however, women <35 years old using their own oocytes displayed a
      similar rate (3.1%) to women using donor oocytes. Eighty MZTs occurred after
      fresh day-5 transfer; only 14 followed fresh day-3 transfer (2.6% vs. 1.2%). The
      MZT incidence in day-3 transfers without hatching was not different from those
      with hatching (1.3% vs. 1.1%). In addition, MZT incidence did not differ
      significantly whether or not ICSI was performed (2.4% vs. 2.0%). Four MZTs
      occurred after frozen-thawed embryo transfer (0.8% incidence). Ninety-five
      percent of all placental arrangements were confirmed as monochorionic-diamniotic
      on obstetric ultrasounds. CONCLUSION(S): These findings confirm a higher
      incidence of MZT after IVF. Monochorionic-diamniotic implantations were
      increased, whereas monochorionic-monoamniotic were not. The MZT risk factors
      included young age and extended culture, but not zona penetration or
      cryopreservation.

PMID- 19409558
TI  - Changing trends in acute upper-GI bleeding: a population-based study.
AB  - BACKGROUND: Advances in medical practice in recent decades have influenced the
      etiology and management of acute upper-GI bleeding (UGIB), but their impact on
      the incidence and mortality is unclear. OBJECTIVE: To analyze the time trends of
      UGIB in 2 different management eras. DESIGN: Prospective observational study.
      SETTING: General university-affiliated hospital. PATIENTS AND INTERVENTIONS: A
      total of 587 patients who presented with UGIB during the 1983-to-1985 period were
      compared with 539 patient in the 2002-to-2004 period. RESULTS: The overall
      incidence of UGIB decreased from 112.5 to 89.8 per 100,000/y, which corresponds
      to a 35.5% decrease after adjustment for age (95% CI, 24.2%-46.8%). The age
      standardized incidence of ulcer bleeding decreased by 41.6% (95% CI, 27.2%-56%);
      the decrease occurred only in people younger than 70 years of age. The rate of
      history of peptic ulcer disease decreased from 32.7% in the 1983-to-1985 period
      versus 19.5% in the 2002-to-2004 period (P < .001). The mean age increased from
      61.0 to 68.7 years (P < .001), and the male:female ratio decreased from 2.7 to
      1.8 (P = .002). The comorbidities increased from 69% to 75% (P = .01), the use of
      nonsteroidal anti-inflammatory drugs from 40.0% to 46.4% (P = .03), and the cases
      of bleeding occurring during hospitalization from 10.4% to 17.1% (P < .001). In
      the 1983-to-1985 cohort, the endoscopy was solely diagnostic, and antisecretory
      therapy consisted of H2-antagonists drugs. In the second period, 39.3% of
      patients underwent endoscopic therapy, whereas proton pump inhibitors were
      administered in 47%. Rebleeding rates decreased from 32.5% to 7.4% (P < .001) and
      surgery from 10.2% to 2.0% (P < .001). Overall mortality decreased from 17.1 to
      8.2 per 100,000/y, which corresponded to a 60.8% decrease after adjustment for
      age (95% CI, 46.5%-75.1%). The age standardized mortality rate for ulcer bleeding
      decreased by 56.5% (95% CI, 41.9%-71.1%). LIMITATIONS: A single-center study and
      a potential lack of generalizability. CONCLUSIONS: From the 1983-to-1985 period
      to the 2002-to-2004 period, major changes occurred in the incidence of UGIB,
      features of patients, management, and outcomes. The incidence and mortality of
      UGIB overall and ulcer bleeding decreased significantly, and the decline of
      incidence occurred only in patients younger than 70 years old.

PMID- 19409557
TI  - Negative influence of paternal age on clinical intracytoplasmic sperm injection
      cycle outcomes in oligozoospermic patients.
AB  - OBJECTIVE: To evaluate the effect of male age on clinical outcomes of
      intracytoplasmic sperm injection (ICSI) cycles, according to sperm concentration.
      DESIGN: Retrospective, observational study. SETTING: Assisted reproduction
      center. PATIENT(S): The study included 1,024 couples undergoing ICSI cycles with
      fresh spermatozoa. INTERVENTION(S): The influence of paternal age on ICSI
      outcomes of oligozoospermic and normozoospermic patients was evaluated. MAIN
      OUTCOME MEASURE(S): Rates of high-quality embryos, pregnancy, implantation, and
      miscarriage were evaluated through linear logistic regression analyses.
      RESULT(S): When the sperm concentration was abnormal, paternal age influenced
      implantation (regression coefficient value = -0.7009) and pregnancy rates (odds
      ratio = 0.95, 95% confidence interval 0.91-0.99). However, in normozoospermic
      patients, no influence of paternal age was observed on implantation (regression
      coefficient value = 0.0566) or pregnancy rates (odds ratio = 1.00, 95% confidence
      interval 0.97-1.03). CONCLUSION(S): For couples in which the men are
      oligozoospermic, the implantation rate could be impaired by increased paternal
      age. In these couples, the chance of pregnancy decreased 5% for each year of
      paternal age. When men are normozoospermic, this effect is not observed.

PMID- 19409559
TI  - Is balloon sweeping detrimental in portal biliopathy? A report of 3 cases.
AB  - BACKGROUND: Portal biliopathy is characterized by biliary obstruction and is
      commonly caused by dilated vascular channels in the pericholedochal plexus
      causing choledochal varices, leading to the formation of stones in the common
      bile duct. Endoscopic treatment leads to severe bleeding complications because of
      the rupture of these vascular channels. OBJECTIVE: We report on our management of
      the unique bleeding complications we faced when performing endotherapy on these
      patients. DESIGN: A case series. SETTING: Single-center experience in a tertiary
      care unit. PATIENTS AND INTERVENTIONS: Patients with portal hypertension and
      choledochal varices, presenting with symptoms of biliary obstruction caused by
      gallstones, were subjected to ERCP and stone removal by use of the balloon
      sweeping and basket extraction techniques. LIMITATION: Small volume case series;
      there is need for a randomized controlled study. CONCLUSION: During stone
      removal, when compared to basket extraction, excessive bleeding was observed when
      balloon sweeping was used because this technique could cause squeezing of the
      choledochal varices.

PMID- 19409560
TI  - Fault detection and diagnosis for singular stochastic systems via B-spline
      expansions.
AB  - This paper deals with the problem of fault detection and diagnosis (FDD) for
      singular stochastic systems. The outputs of singular stochastic systems are
      described by probability density functions (PDFs) based on square root B-spline
      expansions. Then, two non-linear observers are designed for the FDD. The
      conditions of stability of the correlative error estimation systems are given by
      using linear matrix inequalities (LMIs). Finally, the simulation results are
      presented to indicate that the approach can detect faults and estimate the size
      of faults.

PMID- 19409561
TI  - [Comment on "Delayed colo-anal anastomosis after laparoscopic protectomy with
      total mesorectal resection for rectal cancer"].

PMID- 19409563
TI  - Endotoxin as a missed link among all the metabolic abnormalities in the metabolic
      syndrome.

PMID- 19409564
TI  - Lack of association of chromosome 9p21.3 genotype with cardiovascular function in
      persons with stable coronary artery disease: The heart and soul study.

PMID- 19409562
TI  - Candidate genes for respiratory disease associated with markers of inflammation
      and endothelial dysfunction in elderly men.
AB  - BACKGROUND: Inflammation and endothelial dysfunction are important risk factors
      for cardiovascular disease (CVD). We hypothesized that candidate genes selected
      for a study of asthma and chronic obstructive pulmonary disorder (COPD) are
      associated with markers of systemic inflammation and endothelial dysfunction in
      an aging population. METHODS: Plasma levels of circulating C-reactive protein
      (CRP), fibrinogen, intercellular adhesion molecule-1 (ICAM-1) and vascular cell
      adhesion molecule-1 (VCAM-1) were obtained from 679 elderly male participants in
      the Normative Aging Study. Blood samples were analyzed for 202 single nucleotide
      polymorphisms (SNPs) in 25 candidate genes and included both haplotype tagSNPs
      and functional SNPs based on literature review. Data were stratified into
      discovery and replication cohorts for 2-stage analysis. In the discovery cohort,
      the relationship between biomarker level and genotype was analyzed using linear
      mixed effects with random intercepts for each subject and models were adjusted
      for age and BMI. A positive outcome in the discovery cohort was defined as a p
      value <0.1 for the SNP. SNPs that met this criterion were analyzed in the
      replication cohort and confirmed for those which met a criterion of significance
      (p<0.025). RESULTS: In our analyses, SNPs in the CRHR1, ITPR2, and VDR genes met
      significance criteria. CONCLUSIONS: Our results suggest that genes thought to
      play a role in the pathogenesis of asthma and COPD may influence levels of serum
      markers of inflammation and endothelial dysfunction via novel SNP associations
      which have not previously been associated with cardiovascular disease.

PMID- 19409566
TI  - Neopterin predicts the risk for fatal ischemic heart disease in type 2 diabetes
      mellitus: long-term follow-up of the HUNT 1 study.
AB  - AIMS: Neopterin has emerged as a novel predictor of coronary events. The study
      aim was to compare the predictive value of neopterin and C-reactive protein (CRP)
      on long-term risk for fatal ischemic heart disease (IHD) in persons with newly
      diagnosed diabetes compared to persons without diabetes. METHODS AND RESULTS: In
      1984-1986 a large population study, HUNT 1, was conducted in Norway. During the
      study, 205 patients were diagnosed with formerly unknown diabetes. A matched
      control group without diabetes was selected from the HUNT 1 population. Fatal IHD
      was registered until 2004. Blood samples were drawn at baseline and serum was
      analysed for neopterin and CRP. Cox regression analysis with correction for age,
      gender, hypertension, body mass index, established cardiovascular disease and
      total cholesterol was used to estimate hazard ratios (HR) for fatal IHD. In the
      diabetes group, neopterin and CRP were independent predictors of fatal IHD, HR
      2.59 (1.11-6.01) and 2.45 (1.05-5.69), respectively. Neither CRP nor neopterin
      were significant predictors of fatal IHD in the control group. CONCLUSION: In
      subjects with diabetes, both neopterin and CRP were independent predictors of
      fatal IHD, suggesting that these two markers reflect different aspects of the
      pathogenesis underlying fatal coronary events.

PMID- 19409565
TI  - Overexpression of antioxidant enzymes in ApoE-deficient mice suppresses
      benzo(a)pyrene-accelerated atherosclerosis.
AB  - The carcinogenic polycylic aromatic hydrocarbon, benzo(a)pyrene (BaP), has been
      shown to generate reactive oxygen species (ROS) and accelerate the development of
      atherosclerosis. To assess the causal role of BaP-generated ROS in this process,
      we evaluated atherosclerotic metrics in apolipoprotein E-deficient (ApoE(-/-))
      mice with or without overexpression of Cu/Zn-superoxide dismutase (Cu/Zn-SOD)
      and/or catalase. Without BaP, aortic atherosclerotic lesions were smaller in
      ApoE(-/-) mice overexpressing catalase or both Cu/Zn-SOD and catalase than in
      those overexpressing neither or Cu/Zn-SOD only. After treating with BaP or
      vehicle for 24 weeks, mean lesion sizes in the aortic tree and aortic root of
      ApoE(-/-) mice were increased by approximately 60% and 40%, respectively. BaP
      also increased the levels of oxidized lipids in the aortic tree of ApoE(-/-) mice
      and increased the frequency of advanced lesions. In contrast, BaP did not
      significantly alter lipid peroxidation levels or atherosclerotic lesions in the
      aortas of ApoE(-/-) mice overexpressing Cu/Zn-SOD and/or catalase. Overexpression
      of Cu/Zn-SOD and/or catalase also inhibited BaP-induced expression of cell
      adhesion molecules in aortas and endothelial cells, and reduced BaP-induced
      monocyte adhesion to endothelial cells. These observations, together with the
      functions of catalase and Cu/Zn-SOD to scavenge hydrogen peroxide and superoxide
      anions, implicate a causal role of ROS in the pathogenesis of BaP-induced
      atherosclerosis.

PMID- 19409567
TI  - Comparison of in vivo segmental foot motion during walking and step descent in
      patients with midfoot arthritis and matched asymptomatic control subjects.
AB  - The purpose of this study was to compare in vivo segmental foot motion during
      walking and step descent in patients with midfoot arthritis and asymptomatic
      control subjects. Segmental foot motion during walking and step descent was
      assessed using a multi-segment foot model in 30 patients with midfoot arthritis
      and 20 age, gender and BMI matched controls. Peak and total range of motion
      (ROM), referenced to subtalar neutral, were examined for each of the following
      dependent variables: 1st metatarso-phalangeal (MTP1) dorsiflexion, 1st metatarsal
      (MT1) plantarflexion, ankle dorsiflexion, calcaneal eversion and forefoot
      abduction. The results showed that, compared to level walking, step descent
      required greater MTP1 dorsiflexion (p<0.01), MPT1 plantarflexion (p<0.01), ankle
      dorsiflexion (p<0.01), calcaneus eversion (p=0.03) and forefoot abduction
      (p=0.01), in all subjects. In addition, step descent also necessitated greater
      MTP1 dorsiflexion (p<0.01), ankle dorsiflexion (p<0.01) and forefoot abduction
      (p=0.02) excursion compared to walking. Patients with midfoot arthritis responded
      differently to the step task compared to control subjects in terms of MT1 and
      calcaneus eversion excursion. During walking, patients with midfoot arthritis
      showed significantly less MT1 plantarflexion excursion compared to control
      subjects (p=0.03). However, during step descent, both groups showed similar MT1
      plantarflexion excursion. During walking, patients with midfoot arthritis showed
      similar calcaneus eversion excursion compared to control subjects. However,
      during step descent, patients with midfoot arthritis showed significantly greater
      calcaneus eversion excursion compared to control subjects (p=0.03). Independently
      or in combination, these motions may contribute to articular stress and
      consequently to symptoms in patients with midfoot arthritis.

PMID- 19409568
TI  - Isosteric heat of adsorption in liquid-solid equilibria: theoretical
      determination and measurement by liquid chromatography/mass spectrometry.
AB  - The isosteric heat of adsorption of a pure compound dissolved in a solution in
      equilibrium with a solid adsorbent was determined, based on the Gibbs surface
      excess model. The exact isosteric heat of adsorption differs from the usual value
      derived from the variation of the Henry's constant with the reciprocal
      temperature because this procedure assumes ideal behavior of the bulk liquid
      solution, which, in most cases, is only approximately so. An experimental
      protocol, based on the determination of the excess adsorption isotherms by
      combining frontal analysis (for strongly adsorbed components) and spectrometric
      tracer pulse chromatography (for weakly adsorbed compounds) is proposed. It
      allows the determination of the exact isosteric heat of adsorption provided that
      the activity coefficient of the compound in the bulk solution can be explicitly
      expressed as a function of the bulk liquid composition.

PMID- 19409570
TI  - Geranyl acetate emulsions: surfactant association structures and emulsion
      inversion.
AB  - Three emulsions of geranyl acetate (GA)-in-water (W) with identical GA/W ratios
      and varying surfactant (S), Laureth 4, a commercial C(12)EO (4) compound,
      fractions were investigated for nature and stability. The emulsions with up to 6%
      surfactant were W/O, as expected with respect to the solubility of the surfactant
      in the oil. At 10% surfactant, the aqueous phase became the continuous one and
      the apparent stability of the emulsion was significantly enhanced. Analysis of
      the phase diagram and experimental evidence showed the high water content
      emulsion to be a liquid crystal-in-water emulsion; a kind that did not change
      even at extreme O/W and LC/W ratios.

PMID- 19409571
TI  - Lattice Boltzmann method for dynamic wetting problems.
AB  - Wetting is an important phenomenon in many engineering applications. In this
      study, a new algorithm is presented to simulate 2D dynamic wetting phenomena
      using the single phase lattice Boltzmann method (LBM). Basis of our method is an
      additional force at triple points where fluid, gas and wall intersect. This
      supplementary force, which is treated as a capillary force, is able to simulate
      the equilibrium and dynamic wetting behavior of liquids. Based on this method,
      droplet spreading or recoiling on a solid surface and the capillary rise with
      various wetting properties can be simulated successfully. The results of the
      simulation are compared with analytical solutions and experiments. Good agreement
      is achieved for dynamic as well as equilibrium situations.

PMID- 19409569
TI  - Use of high-performance liquid chromatography with diode array detection coupled
      to electrospray-Qq-time-of-flight mass spectrometry for the direct
      characterization of the phenolic fraction in organic commercial juices.
AB  - We have developed a direct method for the qualitative analysis of polyphenols in
      commercial organic fruit juices. The juices were diluted with water (50/50),
      filtered and directly injected. The analysis of phenolic compounds was carried
      out by reversed-phase high-performance liquid chromatography (RP-HPLC) coupled to
      photodiode array detection (DAD) and electrospray ionisation-Qq-time-of-flight
      mass spectrometry (ESI-Qq-TOF-MS). A unique gradient program has been optimized
      for the separation of several phenolic classes and the analysis time was only 5
      min. The fruit juice samples were successfully analysed in positive and negative
      ionisation modes. In positive mode the anthocyanins were identified whereas the
      vast majority of polyphenols were identified using the negative ionisation mode.
      The sensitivity, together with mass accuracy and true isotopic pattern of the Qq
      TOF-MS, allowed the identification of the phenolic compounds. Moreover, the
      advantage of the proposed method is the combined search of MS and MS/MS spectra,
      which improves the identification of compounds considerably, reducing ambiguities
      and false positive hits. Therefore the total fragmentation of the compound ion
      leading to the aglycone ion or other fragments was corroborated by MS-MS. The
      method was successfully employed to characterize diverse phenolic families in
      commercially available organic juices from four different fruits and consequently
      could be used in the future for the quantification purposes to compare different
      content of polyphenols in juices.

PMID- 19409572
TI  - Influence of particle size on shear behavior of amine-group-immobilized
      polyacrylonitrile dispersed suspension under electric field.
AB  - Different-sized particles dispersed electrorheological (ER) fluids were
      fabricated with poly(acryloamidino diethylenediamine) to observe the influence of
      the particle size on ER behaviors. The fine particles dispersed ER suspension
      showed stable shear stress under a DC electric field. On the other hand, the
      rough particles dispersed suspension showed trembling shear stress which is
      divided into four regions in a plot of shear stress against shear rate. Our
      suggested spring-damper model equation treated the wide range of shear rate and
      specific (trembling) behaviors of shear stress in ER fluids. In this study, we
      successfully obtained various ER fluids showing different behaviors just by
      changing the size of particles in the ER fluids. All of the curves of the shear
      stress plotted against shear rate were fitted well by our spring-damper model.

PMID- 19409573
TI  - Kinetics of adsorption of whey proteins and hydroxypropyl-methyl-cellulose
      mixtures at the air-water interface.
AB  - The aim of this research is to quantify the competitive adsorption of a whey
      protein concentrate (WPC) and hydroxypropyl-methyl-cellulose (HPMC so called E4M,
      E50LV and F4M) at the air-water interface by means of dynamic surface tensiometry
      and Brewster angle microscopy (BAM). These biopolymers are often used together in
      many food applications. The concentration of both protein and HPMC, and the
      WPC/HPMC ratio in the aqueous bulk phase were variables, while pH (7), the ionic
      strength (0.05 M) and temperature (20 degrees C) were kept constant. The
      differences observed between mixed systems were in accordance with the relative
      bulk concentration of these biopolymers (C(HPMC) and C(WPC)) and the molecular
      structure of HPMC. At short adsorption times, the results show that under
      conditions where both WPC and HPMC could saturate the air-water interface on
      their own or when C(HPMC) > or = C(WPC), the polysaccharide dominates the
      surface. At concentrations where none of the biopolymers was able to saturate the
      interface, a synergistic behavior was observed for HPMC with lower surface
      activity (E50LV and F4M), while a competitive adsorption was observed for E4M
      (the HPMC with the highest surface activity). At long-term adsorption the rate of
      penetration controls the adsorption of mixed components. The results reflect
      complex competitive/synergistic phenomena under conditions of thermodynamic
      compatibility or in the presence of a "depletion mechanism". Finally, the order
      in which the different components reach the interface will influence the surface
      composition and the film properties.

PMID- 19409574
TI  - Evolving the language-ready brain and the social mechanisms that support
      language.
AB  - We first review the mirror-system hypothesis on the evolution of the language
      ready brain, stressing the important role of imitation and protosign in providing
      the scaffolding for protospeech. We then assess the role of social interaction
      and non-specific knowledge of language in the emergence of new sign languages in
      deaf communities (focusing on Nicaraguan Sign Language). LEARNING OUTCOMES: (1)
      Readers will understand the difference between mirror systems in humans and
      monkeys, and see how the evolution of imitation and protosign required the
      biological evolution of mirror systems with linkages to diverse regions beyond
      the mirror system. (2) Readers will see how social structure complements brain
      mechanisms in yielding language through cultural evolution supported by having
      language-ready brains, rather than through possession of an innate Universal
      Grammar. (3) Readers will understand that ontogeny does not recapitulate
      phylogeny, but will appreciate what mechanisms currently operative in modern
      children acquiring language may also have served early humans during the
      cumulative invention of the idea of language.

PMID- 19409575
TI  - Changes in sediment and organic carbon accumulation in a highly-disturbed
      ecosystem: the Sacramento-San Joaquin River Delta (California, USA).
AB  - We used the Sacramento-San Joaquin River Delta CA (Delta, hereafter) as a model
      system for understanding how human activities influence the delivery of sediment
      and total organic carbon (TOC) over the past 50-60 years. Sediment cores were
      collected from sites within the Delta representing the Sacramento River (SAC),
      the San Joaquin River (SJR), and Franks Tract (FT), a flooded agricultural tract.
      A variety of anthropogenic tracers including (137)Cs, total DDE (Sigma DDE) and
      brominated diphenyl ether (BDE) congeners were used to quantify sediment
      accumulation rates. This information was combined with total organic carbon (TOC)
      profiles to quantify rates of TOC accumulation. Across the three sites, sediment
      and TOC accumulation rates were four to eight-fold higher prior to 1972. Changes
      in sediment and TOC accumulation were coincident with completion of several large
      reservoirs and increased agriculture and urbanization in the Delta watershed.
      Radiocarbon content of TOC indicated that much of the carbon delivered to the
      Delta is "pre-aged" reflecting processing in the Delta watershed or during
      transport to the sites rather than an input of predominantly contemporary carbon
      (e.g., 900-1400 years BP in surface sediments and 2200 yrs BP and 3610 yrs BP at
      the base of the SJR and FT cores, respectively). Together, these data suggest
      that human activities have altered the amount and age of TOC accumulating in the
      Delta since the 1940s.

PMID- 19409576
TI  - What a pile of old rubbish!

PMID- 19409577
TI  - Analysis of community structure of a microbial consortium capable of degrading
      benzo(a)pyrene by DGGE.
AB  - A microbial consortium was obtained by enrichment culture of sea water samples
      collected from Botan oil port in Xiamen, China, using the persistent high
      concentration of a mixture of polycyclic aromatic hydrocarbons enrichment
      strategy. Denaturing gradient gel electrophoresis (DGGE) was used to investigate
      the bacterial composition and community dynamic changes based on PCR
      amplification of 16S rRNA genes during batch culture enrichment. Using the spray
      plate method, three bacteria, designated as BL01, BL02 and BL03, which
      corresponded to the dominant bands in the DGGE profiles, were isolated from the
      consortium. Sequence analysis showed that BL01, BL02 and BL03 were
      phylogenetically close to Ochrobactrum sp., Stenotrophomonas maltophilia and
      Pseudomonas fluorescens, respectively. The degradation of benzo(a)pyrene (BaP), a
      model high-molecular-weight polycyclic aromatic hydrocarbon (HMW PAH) compound
      was investigated using individual isolates, a mixture of the three isolates, and
      the microbial consortium (BL) originally isolated from the oil port sea water.
      Results showed that the order of degradative ability was BL>the mixture of the
      three isolates>individual isolates. BL degraded 44.07% of the 10 ppm BaP after 14
      days incubation, which showed the highest capability for HMW PAH compound
      degradation.Our results revealed that this high selective pressure strategy was
      feasible and effective in enriching the HMW PAH-degraders from the original sea
      water samples.

PMID- 19409579
TI  - Purification and biochemical characterization of a serine proteinase inhibitor
      from Derris trifoliata Lour. seeds: insight into structural and antimalarial
      features.
AB  - A potent serine proteinase inhibitor was isolated and characterized from the
      seeds of the tropical legume liana, Derris trifoliata (DtTCI) by ammonium sulfate
      precipitation, ion exchange chromatography and gel filtration chromatography. SDS
      PAGE as well as MALDI-TOF analysis showed that DtTCI is a single polypeptide
      chain with a molecular mass of approximately 20 kDa. DtTCI has three
      isoinhibitors (pI: 4.55, 5.34 and 5.72) and, inhibited both trypsin and
      chymotrypsin in a 1:1 molar ratio. Both Dixon plots and Lineweaver-Burk double
      reciprocal plots revealed a competitive inhibition of trypsin and chymotrypsin
      activity, with inhibition constants (K(i)) of 1.7x10(-10) and 1.25x10(-10) M,
      respectively. N-terminal sequence of DtTCI showed over 50% similarity with
      numerous Kunitz-type inhibitors of the Papilionoideae subfamily. High pH
      amplitude and broad temperature optima were noted for DtTCI, and time course
      experiments indicated a gradual loss in inhibitory potency on treatment with
      dithiothreitol (DTT). Circular Dichroism (CD) spectrum of native DtTCI revealed
      an unordered structure whereas exposure to thermal-pH extremes, DTT and guanidine
      hydrochloride (Gdn HCl) suggested that an abundance of beta-sheets along with
      intramolecular disulfide bonds provide conformational stability to the active
      site of DtTCI, and that severity of denaturants cause structural modifications
      promoting inhibitory inactivity. Antimalarial studies of DtTCI indicate it to be
      a potent antiparasitic agent.

PMID- 19409578
TI  - Long-term weight loss decreases the nontraditional cardiovascular risk factors
      interleukin-18 and matrix metalloproteinase-9 in obese subjects.
AB  - The objective of the study was to investigate the effect of long-term (3.2 years)
      weight loss on serum levels of the nontraditional cardiovascular risk factors
      interleukin (IL)-18 and matrix metalloproteinase (MMP)-9. Moreover, we wanted to
      assess the significance of the magnitude of the weight loss and evaluate the
      potential effects of 36 months of treatment with the lipase inhibitor orlistat on
      these parameters. Sixty-eight abdominally obese subjects completed 8 weeks of
      very low energy diet (600-800 kcal/d) followed by 36 months of randomized
      treatment with either orlistat or placebo together with lifestyle intervention.
      Serum levels of IL-18, MMP-9, and leptin were measured by flowmetric xMAP
      technology (Luminex, Austin, TX). Changes in the levels of IL-18, MMP-9, and
      leptin were similar in the orlistat and the placebo group during this study.
      Thus, the 2 groups were combined for further analysis. A weight loss of 8.4 +/-
      8.8 kg from baseline to 3.2 years was associated with significant decreases in IL
      18 (P < .001), MMP-9 (P < .01), and leptin (P < .001). Matrix metalloproteinase-9
      was, however, significantly increased after 8 weeks of very low energy diet
      induced weight loss (P < .05). The long-term changes in IL-18 were significantly
      associated with changes in body mass index independent of changes in blood
      pressure and lipids (P < .05). Levels and changes of IL-18 and MMP-9 were
      significantly positively associated at 3.2 years (P < .01). Long-term changes in
      leptin were significantly associated with changes in IL-18 (P < .01) at 3.2
      years. Diet-induced long-term weight loss decreased IL-18 and MMP-9. The decrease
      in IL-18 was associated with changes in body mass index independent of changes in
      blood pressure and lipids, indicating that even a minor weight reduction (>5%)
      has beneficial effects on nontraditional cardiovascular risk markers. Orlistat
      treatment had no independent effects on IL-18, MMP-9, or leptin in the present
      study.

PMID- 19409580
TI  - Triterpenoid saponins from Impatiens siculifer.
AB  - Triterpenoid saponins, impatienosides A-G, together with 12 known saponins, were
      isolated from the whole plants of Impatiens siculifer. Their structures were
      established on the basis of extensive 1D and 2D NMR and MS analyses coupled with
      chemical degradation. Cytotoxic activities of the isolated saponins were
      evaluated against three human cancer cell lines: human myeloid leukemia HL-60
      cells, human stomach KATO-III adenocarcinoma, and human lung A549 adenocarcinoma.

PMID- 19409581
TI  - Iridoids from Gentiana loureirii.
AB  - Iridoid glycosides, 2',3',6'-tri-O-acetyl-4'-O-trans-p-(O-beta-d
      glucopyranosyl)coumaroyl-7-ketologanin (1), 2'-O-caffeoylloganic acid (2), 2'-O-p
      hydroxybenzoylloganic acid (3), 2'-O-trans-p-coumaroylloganic acid (4), and 2'-O
      cis-p-coumaroylloganic acid (5), were isolated from whole plants of Gentiana
      loureirii along with six known iridoids, 7-ketologanin (6), loganin (7), loganic
      acid (8), sweroside, boonein, and isoboonein, and three other known compounds.
      Their structures were elucidated by spectroscopic means and chemical
      correlations. The isolated iridoids were evaluated for antibacterial and
      antioxidant activities, but were either inactive or very weakly active.

PMID- 19409582
TI  - The leaf, inner bark and latex cyanide potential of Hevea brasiliensis: evidence
      for involvement of cyanogenic glucosides in rubber yield.
AB  - The latex of Hevea brasiliensis, expelled upon bark tapping, is the cytoplasm of
      anastomosed latex cells in the inner bark of the rubber tree. Latex regeneration
      between two tappings is one of the major limiting factors of rubber yield. Hevea
      species contain high amounts of cyanogenic glucosides from which cyanide is
      released when the plant is damaged providing an efficient defense mechanism
      against herbivores. In H. brasiliensis, the cyanogenic glucosides mainly consist
      of the monoglucoside linamarin (synthesized in the leaves), and its diglucoside
      transport-form, linustatin. Variations in leaf cyanide potential (CNp) were
      studied using various parameters. Results showed that the younger the leaf, the
      higher the CNp. Leaf CNp greatly decreased when leaves were directly exposed to
      sunlight. These results allowed us to determine the best leaf sampling conditions
      for the comparison of leaf CNp. Under these conditions, leaf CNp was found to
      vary from less than 25 mM to more than 60 mM. The rubber clones containing the
      highest leaf CNp were those with the highest yield potential. In mature virgin
      trees, the CNp of the trunk inner bark was shown to be proportional to leaf CNp
      and to decrease on tapping. However, the latex itself exhibited very low (if any)
      CNp, while harboring all the enzymes (beta-D-diglucosidase, linamarase and beta
      cyanoalanine synthase) necessary to metabolize cyanogenic glucosides to generate
      non-cyanogenic compounds, such as asparagine. This suggests that in the rubber
      tree bark, cyanogenic glucosides may be a source of buffering nitrogen and
      glucose, thereby contributing to latex regeneration/production.

PMID- 19409583
TI  - [Optimization of the dose of radiation in shoulder arthrography].
AB  - OBJECTIVE: The aim of this study was to determine whether using a film with
      radiopaque coordinates placed over the region of interest to guide shoulder
      arthrography can reduce the dose of radiation received by patients. MATERIAL AND
      METHODS: The entrance dose was obtained in 34 patients (mean age, 44 years;
      range, 15 to 75 years). The dose received by organs at risk and the effective
      dose were estimated with Monte Carlo techniques using the following input
      parameters: patient anatomy, examination geometry, and air kerma at the entrance
      to the patient without backscattering. Arthrography was performed with a remote
      controlled device and images were acquired digitally without fluoroscopy.
      RESULTS: The mean thickness of the shoulders studied was 14.6+/-2.1cm (9-20 cm).
      Images were obtained with 80+/-10 kVp (60-85 kVp) and 6.5+/-3.5 mAs (1.4-17 mAs).
      The mean time of irradiation for each patient was 20+/-6 ms (6.9-47.9 ms). The
      calculated air kerma was 0.41+/-0.19 mGy and the effective dose was 0.79+/-0.40
      muSv. CONCLUSIONS: The technique described in this study has enabled us to reduce
      the dose of radiation received by patients undergoing shoulder arthrography in
      comparison with other techniques described in the literature and to ensure that
      the radiologist performing the procedure is not irradiated.

PMID- 19409584
TI  - Detection of Fusobacterium necrophorum and Dichelobacter nodosus in lame cattle
      on dairy farms in New Zealand.
AB  - Lameness in the dairy industry in New Zealand causes a problem in lost
      production, animal welfare and associated costs. To understand what bacteria may
      be present on the hooves of lame dairy cattle in this grass-fed system, samples
      were scraped from lame dairy cows and examined for the presence of Fusobacterium
      necrophorum (F. necrophorum) and Dichelobacter nodosus (D. nodosus) using the
      polymerase chain reaction (PCR). The PCR primers were designed to detect the
      presence of the lktA gene, which encodes a leukotoxin unique to F. necrophorum,
      and the fimA gene of D. nodosus. A total of 148 hoof scrapings were collected by
      farm staff over the period September 2005 to May 2006. F. necrophorum was
      detected in 79/148 of the samples, while D. nodosus was detected in 7/148 of the
      samples. The frequent finding of F. necrophorum within dairy herds in New Zealand
      is noteworthy and the occasional finding of D. nodosus on some dairy cattle
      suggests a possible role in both ovine and bovine hoof pathology.

PMID- 19409585
TI  - Method for co-purification of equine neutrophil elastase and myeloperoxidase from
      a limited blood volume.
AB  - Neutrophil myeloperoxidase (MPO) and elastase can be released in severe
      inflammatory diseases and cause tissue injuries. Equine enzymes have already been
      individually purified from large blood quantities. We describe the isolation of
      both enzymes from a same limited blood volume. Both MPO and elastase were
      extracted by crushing PMN isolated by centrifugation on a percoll-gradient from a
      460 ml blood collection. MPO and elastase were separated by an ionic exchange
      chromatography phase and further purified by gel filtration chromatography on
      Superdex 200 and 75, respectively. Enzymes were identified in the collected
      fractions by specific enzymatic assays. The final purity was verified by
      electrophoresis. Specific activity was improved to 19.92 and 34.3 x for elastase
      (final yield: 340 microg) and MPO (final yield: 130 microg), respectively, during
      the procedure. Results show the possibility of isolating both enzymes from the
      same blood sample with a sufficient yield and purity for future studies on their
      implication and interaction during inflammatory diseases.

PMID- 19409586
TI  - [Pneumomediastinum, a rare complication secondary to a minor maxillary fracture].
AB  - OBSERVATION: A pneumomediastinum was discovered fortuitously on a CT scan
      prescribed to a patient for facial and cranial trauma. Emphysema was attributed
      secondarily to an anterolateral maxillary wall fracture. The evolution was
      favorable after simple clinical and radiological surveillance. DISCUSSION: The
      observation of a pneumomediastinum should first be related to a tracheal or
      esophageal wound with a severe prognosis. Endoscopy under general anesthesia was
      not necessary for our patient thanks to CT scan with 3D reconstruction. There is
      no consensus for systematic antibioprophylaxis.

PMID- 19409587
TI  - [Occlusal splint: state of the art].
AB  - Occlusal splint are defined as intra-oral devices mostly indicated to modify the
      occlusal relationship between maxillar and mandibular dental arches. Among the
      different shapes of occlusal splint, an updating seemed necessary to the authors.
      The main indications for occlusal splint are represented by temporomandibular
      disorders and teeth protection. Occlusal splints are usually made of hard resin
      and are, generally, carried on the mandibular jaw. Total occlusal splint are
      preferable to partial occlusal splint, except in some emergent cases. The smooth
      occlusal splints are needed for musculo-articular disorders when the indentated
      splints are reserved for mandibular repositioning in articular temporomandibular
      joint disorders.

PMID- 19409588
TI  - The epidemiology and control of urinary schistosomiasis and soil-transmitted
      helminthiasis in schoolchildren on Unguja Island, Zanzibar.
AB  - As part of a 4-year control programme beginning in 2003 and entitled Piga Vita
      Kichocho, around 140,000 school-aged children on Unguja Island, Zanzibar were
      treated annually with a combination of praziquantel and albendazole. To provide
      information on the impact of this intervention, a subset of children, originating
      from 24 sentinel schools, were monitored in 2004, 2005 and 2006 using both
      parasitological and behavioural questionnaire methods. Overall, prevalence of
      urinary schistosomiasis fell by 52%, intensity by 55% and gross haematuria by
      82%. There was a positive and statistically significant correlation between areas
      of elevated disease prevalence and areas of predicted high transmission based
      upon local occurrence of the permissive intermediate snail host. In areas of low
      transmission, urinary schistosomiasis was greatly reduced, but, by contrast,
      other intervention strategies are needed to complement and synergise with
      chemotherapy in high transmission areas. Whereas significant reductions were
      documented in the prevalence of both Trichuris trichiura and hookworm, prevalence
      of Ascaris lumbricoides significantly increased over the monitoring period.
      Through a detailed analysis of named child records, evidence of predisposition to
      helminth (re)infection and individual bias towards polyparasitism was detected,
      highlighting the often overlapping distribution of these parasites within the
      school-aged child.

PMID- 19409589
TI  - The acute phase response in children with mild and severe malaria in Papua New
      Guinea.
AB  - The production of acute phase proteins during infection is an important part of
      innate immunity and limits inflammation. However, little is known of the acute
      phase response in malaria. We measured acute phase proteins in plasma in children
      attending clinics and admitted to hospital with acute malaria in Papua New
      Guinea. Plasma ferritin concentration increased progressively with disease
      severity with markedly elevated levels in the most severely ill children. Plasma
      ferritin was >500 ng/ml in 7/99 (7.1%) outpatients with uncomplicated malaria,
      22/100 (22.0%) hospital non-severe cases, 64/175 (36.6%) severe malaria cases who
      survived and 7/9 (77.8%) severe malaria deaths (P<0.001). The greatest
      concentration of ferritin (3561 ng/ml) was observed in a child who died. By
      contrast, C-reactive protein concentration was markedly increased in 153 children
      with uncomplicated malaria [median 203 (interquartile range 51-365) microg/ml]
      but, surprisingly, was only moderately increased in 135 children with one or more
      severe manifestations of malaria [47 (17-97) microg/ml; P<0.001] and in 6
      children who died [41 (22-280) microg/ml]. Excessive free-radical damage
      resulting from a combination of iron-induced oxidant stress and reduced levels of
      C-reactive protein may be an important pathological mechanism in severe malaria
      and amenable to therapeutic intervention.

PMID- 19409590
TI  - Malnutrition among children in rural Malawian fish-farming households.
AB  - To estimate the impact of fish farming operated at household level on nutritional
      status among children 6-59 months of age, a cross-sectional study was conducted
      in Zomba district, Malawi. Anthropometric measurements of 66 children in each
      type of household (fish-farming and non-fish-farming households) and structured
      interviews with their parents were undertaken. A total of 21 background variables
      were employed and examined using bivariate and multivariate analyses. Overall, a
      lower prevalence of malnutrition was detected among the children in fish-farming
      households than those in non-fish-farming households in all the malnutrition
      indicators, i.e. stunting, underweight and wasting. In particular, a
      significantly lower prevalence was detected among the children in fish-farming
      households than those in non-fish-farming households in both severe (P=0.045) and
      global underweight (P=0.042). 'Higher proportion of income from fish farming to
      total income', 'more frequent intake of oil and fats other than never/seldom' and
      'breastfeeding practice for the appropriate duration' are the protective factors
      against being underweight. Household fish farming may have indirectly contributed
      to lower prevalence of underweight through increasing frequency of intake of oil
      and fats by strengthening households' purchasing power. The study supports 12
      months as the threshold for appropriate breastfeeding duration.

PMID- 19409592
TI  - Optical calibration for both out-of-plane and in-plane displacement sensitivity
      of acoustic emission sensors.
AB  - The use of piezoelectric sensors for acoustic emission (AE) monitoring provides
      an extremely sensitive detection method of AE events. The sensors are used to
      detect the stress waves, resulting from an AE event, which arrive at the surface
      of a structure. The sensors provide high sensitivity, and are generally based on
      a high-Q design where the sensor is used to detect AE events around its
      resonance. Sensitivity calibration of these sensors is essential for accurate
      assessment of the AE measurement and particularly important for sensors mounted
      on safety critical structures. This paper proposes an optical method which
      enables both the out-of-plane and in-plane displacement sensitivity of an AE
      sensor to be established independently from each other. In the method, a laser
      homodyne interferometer is used to measure the out-of-plane and in-plane
      displacement of the surface of a large test block excited by a repeatable source
      transducer. The out-of-plane displacement is measured by aligning the laser beam
      perpendicular to the surface with time gating of the receive waveform used to
      isolate only the direct arrival of the longitudinal wave produced by the piston
      source transducer. For the in-plane displacement measurement, the laser beam is
      aligned parallel to the surface to intersect a small optically reflective step
      with the time waveform being gated to measure only the direct shear arrival
      produced using a normal incidence shear wave source transducer. In each case, the
      interferometer measurement is followed by coupling the sensor under test to the
      measurement surface, which is then exposed to the same acoustic field and the
      sensor output signal measured. This substitution method allows the sensor
      sensitivity to be obtained in terms of volts per unit displacement for both the
      out-of-plane and the in-plane surface displacement. The method provides a
      comprehensive description of an AE sensor response to different planes of
      displacement and offers the potential for a traceable sensor calibration to units
      of length.

PMID- 19409591
TI  - Volume quantification by fuzzy logic modelling in freehand ultrasound imaging.
AB  - INTRODUCTION: Many algorithms exist for 3D reconstruction of data from freehand
      2D ultrasound slices. These methods are based on interpolation techniques to fill
      the voxels from the pixels. For quantification purposes, segmentation is involved
      to delineate the structure of interest. However, speckle and partial volume
      effect errors can affect quantification. OBJECTIVE: This study aimed to assess
      the effect of the combination of a fuzzy model and 3D reconstruction algorithms
      of freehand ultrasound images on these errors. METHODS: We introduced a
      fuzzification step to correct the initial segmentation, by weighting the pixels
      by a distribution function, taking into account the local gray levels, the
      orientation of the local gradient, and the local contrast-to-noise ratio. We then
      used two of the most wide-spread reconstruction algorithms (pixel nearest
      neighbour (PNN) and voxel nearest neighbour (VNN)) to interpolate and create the
      volume of the structure. Finally, defuzzification was used to estimate the
      optimal volume. VALIDATION: B-scans were acquired using 5 MHz and 8 MHz
      ultrasound probes on ultrasound tissue-mimicking phantoms. Quantitative
      evaluation of the reconstructed structures was done by comparing the method
      output to the real volumes. Comparison was also done with classical PNN and VNN
      algorithms. RESULTS: With the fuzzy model quantification errors were less than
      4.3%, whereas with classical algorithms, errors were larger (10.3% using PNN,
      17.2% using VNN). Furthermore, for very small structures (0.5 cm(3)), errors
      reached 24.3% using the classical VNN algorithm, while they were about 9.6% with
      the fuzzy VNN model. CONCLUSION: These experiments prove that the fuzzy model
      allows volumes to be determined with better accuracy and reproducibility,
      especially for small structures (<3 cm(3)).

PMID- 19409593
TI  - Enhanced papillomavirus-like particle production in insect cells.
AB  - Human papillomavirus (HPV) L1 self-assembles into virus-like particles (VLPs),
      which are the basis for the two commercially available prophylactic vaccines. For
      one of them (Cervarix) HPV 16 and 18 VLPs are being produced in insect cells
      using the baculovirus expression system. However, due to low yield, production of
      VLPs remains challenging for certain other PV types. Here we report that
      employment of a modified baculovirus-based (MultiBac) expression system (Berger,
      I., Fitzgerald, D. J., and Richmond, T. J. (2004). Baculovirus expression system
      for heterologous multiprotein complexes. Nat. Biotechnol. 22(12), 1583-7) permits
      substantially improved VLP production of several PV types up to 40-fold. Highest
      VLP yields were achieved when two copies of the L1 gene were expressed from
      independently controlled cassettes. We have evaluated the production of HPV 57 L1
      VLPs by the MultiBac system in more detail. Whereas the level of the HPV 57 L1
      protein was only slightly increased in comparison to the standard protocol we
      monitored a strongly enhanced yield of HPV 57 VLPs. Our results imply that a
      critical concentration of L1 within the producer cell is required for efficient
      VLPs assembly. We show evidence that in addition a dominant negative factor in
      conventionally produced recombinant baculoviruses contributes to differences in
      VLP yield. This phenomenon might be attributable to the absence of the viral
      cysteine protease V-CATH in the modified baculovirus system. We anticipate that
      use of the MultiBac expression system will facilitate capsid production for
      papillomaviruses and thereby enable the generation of vaccines against infections
      by many of the as yet untargeted HPV types.

PMID- 19409594
TI  - Inhibition of major histocompatibility complex Class I antigen presentation by
      hepatitis C virus core protein in myeloid dendritic cells.
AB  - Hepatitis C virus core (HCVcore) protein was expressed in myeloid dendritic cells
      (DC) from C57/B6 mice (H-2K(b)) by electroporation of HCVcore mRNA to investigate
      its effect on the ability of DC to prime CD8+ T cells displaying a T cell
      receptor specific for OVA(257-264) peptide (SIINFEKL)/H-2K(b) complex. Expression
      of full length HCVcore(191), which is directed to the endoplasmic reticulum (ER)
      membrane by a C-terminal signal sequence, but not a truncated variant
      HCVcore(152), which has a wider subcellular localization including the nucleus,
      significantly reduced surface levels of the H-2K(b)/SIINFEKL complex and impaired
      the ability of DC to prime naive CD8+ T cells when they had to process endogenous
      antigen but not when MHC class I molecules were loaded directly with SIINFEKL
      peptide. Exploitation of the MHC class I antigen-processing pathway by
      HCVcore(191) impairs the ability of DC to stimulate CD8+ T cells and may
      contribute to the persistence of HCV infection.

PMID- 19409596
TI  - The conserved baculovirus protein p33 (Ac92) is a flavin adenine dinucleotide
      linked sulfhydryl oxidase.
AB  - Open reading frame 92 of the Autographa californica baculovirus (Ac92) is one of
      about 30 core genes present in all sequenced baculovirus genomes. Computer
      analyses predicted that the Ac92 encoded protein (called p33) and several of its
      baculovirus orthologs were related to a family of flavin adenine dinucleotide
      (FAD)-linked sulfhydryl oxidases. Alignment of these proteins indicated that,
      although they were highly diverse, a number of amino acids in common with the
      Erv1p/Alrp family of sulfhydryl oxidases are present. Some of these conserved
      amino acids are predicted to stack against the isoalloxazine and adenine
      components of FAD, whereas others are involved in electron transfer. To
      investigate this relationship, Ac92 was expressed in bacteria as a His-tagged
      fusion protein, purified, and characterized both spectrophotometrically and for
      its enzymatic activity. The purified protein was found to have the color (yellow)
      and absorption spectrum consistent with it being a FAD-containing protein.
      Furthermore, it was demonstrated to have sulfhydryl oxidase activity using
      dithiothreitol and thioredoxin as substrates.

PMID- 19409595
TI  - Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like
      protease cause different conformational changes in crystal structure.
AB  - The 3C-like protease of SARS coronavirus (SARS-CoV 3CL(pro)) is vital for SARS
      CoV replication and is a promising drug target. It has been extensively proved
      that only the dimeric enzyme is active. Here we discovered that two adjacent
      mutations (Ser139_Ala and Phe140_Ala) on the dimer interface resulted in
      completely different crystal structures of the enzyme, demonstrating the distinct
      roles of these two residues in maintaining the active conformation of SARS-CoV
      3CL(pro). S139A is a monomer that is structurally similar to the two reported
      monomers G11A and R298A. However, this mutant still retains a small fraction of
      dimer in solution, which might account for its remaining activity. F140A is a
      dimer with the most collapsed active pocket discovered so far, well-reflecting
      the stabilizing role of this residue. Moreover, a plausible dimerization
      mechanism was also deduced from structural analysis. Our work is expected to
      provide insight on the dimerization-function relationship of SARS-CoV 3CL(pro).

PMID- 19409597
TI  - Surfactant cytotoxicity assay based on a silicon transducer.
AB  - A cytotoxicity assay for surfactants was developed using a potentiometric silicon
      transducer and Lactobacillus plantarum (NBRC3070), and the results are reported
      here. L. plantarum was used as the test microorganism for assaying the
      cytotoxicity of the surfactants. The extracellular pH change resulting from the
      metabolic pathway was measured by a light-addressable potentiometric sensor. This
      potentiometric sensor system measured the acidification of the L. plantarum
      medium; acidification resulting from metabolic activity was inhibited by the
      toxic activity of the surfactant. Results indicated that the anionic surfactant
      did not exhibit inhibitory activity in either cell growth or extracellular
      acidification until 0.2mM. By contrast, the inhibition activity of cationic
      surfactants toward cellular growth and metabolic activity was greater than that
      of anionic surfactants. These results are consistent with those from the growth
      inhibition assay.

PMID- 19409598
TI  - Nonylphenol and octylphenol in adipose tissue of women in Southern Spain.
AB  - Alkylphenols (APs) and AP ethoxylates are environmental contaminants with
      endocrine disrupting activities in wildlife and humans. They have been largely
      used in industrial, agricultural, and domestic applications. Despite strong
      concerns about the consequences of human exposure to endocrine disrupters, little
      information is available on the presence in humans of compounds such as APs. The
      aim of the present study was to determine 4-nonylphenol (NP) and 4-octylphenol
      (OP) residues in adipose tissue of non-occupationally exposed women living in
      Southern Spain. NP was detected in 100% (n=20/20) and OP in 23.5% (n=4/20) of
      samples, with median levels of 57 and 4.5 ng g(-1) adipose tissue, respectively.
      Body mass index emerged as a determinant of exposure since it was associated with
      NP levels (p=0.041). Adipose tissue NP and OP levels are similar to the few data
      previously published in other countries. This is the first report on NP and OP
      levels in a population in Southern Spain. Further research is needed to determine
      trends in human exposure to these compounds and to investigate their
      consequences.

PMID- 19409599
TI  - Evaluation of simultaneous nutrient removal and sludge reduction using laboratory
      scale sequencing batch reactors.
AB  - The treatment and disposal of excess sludge has been a rising challenge for
      wastewater treatment plants worldwide. In this study, simultaneous sludge
      reduction and nutrient removal was evaluated in laboratory scale sequencing batch
      reactors (SBRs). Two SBRs were operated alongside for a duration of 370d. One SBR
      was operated to achieve nutrient removal (control-SBR) at 10d solids retention
      time (SRT), while the other (modified-SBR) was operated to achieve nutrient
      removal along with sludge reduction. Sludge reduction in the modified-SBR was
      accomplished by subjecting the recycled biomass to feasting and fasting at
      sufficiently high SRT close to infinity (phase I and II) and finite SRT (phase
      III). The observed biomass yield in the modified-SBR was estimated to be 0.17mg
      TSSmg(-1) COD, representing 63% sludge reduction compared to the control-SBR. The
      NH(3) levels in the effluents from both SBRs always remained below detection
      limit. The average dissolved phosphorus removal efficiencies in the control-SBR
      and the modified-SBR were 87% and 84%, respectively, during phase II. However,
      the biomass of the modified-SBR increased during phase II. To control this,
      biomass wastage was initiated directly from the modified-SBR during phase III at
      a rate equivalent to the observed biomass accumulation rate in the system in
      phase II. This resulted in an overall 100d SRT for the modified-SBR system.
      Following this change, biomass accumulation in the modified-SBR was controlled,
      and a net 63% sludge reduction could be sustained along with 90% phosphorus and
      100% NH3 removal. Consistent denitrification activities were also noticed in both
      SBRs despite the absence of any carbon source during the anoxic phase of every
      cycle.

PMID- 19409600
TI  - Seasonal changes and temperature-dependent accumulation of polycyclic aromatic
      hydrocarbons in high-altitude soils.
AB  - Polycyclic Aromatic Hydrocarbons (PAHs) are a major group of pollutants whose
      occurrence in the environment is mainly of anthropogenic origin. In this paper,
      we examine the effect of topographical slope exposure on PAH contamination and
      seasonal change in PAH concentrations in soils. We collected soil samples on
      three dates in 2007 (early May, end of July and beginning of November) from south
      and north-facing aspects at 1900 m a.s.l. in the central Italian Alps. We found
      greater PAH contamination in soils from a north-facing slope than in those from a
      south-facing slope at all seasons. We calculated North-South Enrichment Factors
      as the ratio between the concentrations measured in soils from northern and
      southern aspects. These ratios ranged from 1.4 to 1.9 for lighter PAHs (from 2 to
      4 rings). These values are consistent with theoretical calculations based on
      temperature-specific octanol-air partition coefficients (predicted North-South
      Enrichment Factors range from 1.6 to 2.0). For heavier PAHs (from 5 to 6 rings),
      smaller differences were observed between soils from northern and southern
      aspects, due to the gas/particle distribution of these compounds. We also found
      consistent differences in normalised PAH concentrations across the three sampling
      periods. The majority of compounds showed a significant decreasing trend from the
      beginning of May to the end of July, due to the annual cycles of physical
      processes (deposition vs. volatilisation) and biological processes (uptake and/or
      biotransformation). Only a few compounds showed different trends, presumably due
      to season-specific local emission sources.

PMID- 19409601
TI  - G-455A polymorphism of beta-fibrinogen gene and the risk of premature myocardial
      infarction in Greece.
AB  - INTRODUCTION: There are limited and controversial data regarding the impact of G
      455A polymorphism of beta-fibrinogen gene in the pathogenesis of premature
      myocardial infarction (MI). We examined whether the G-455A polymorphism of beta
      fibrinogen gene is associated with the development of MI< or =35 years of age.
      METHODS: We recruited 181 consecutive patients who had survived their first acute
      MI< or =35 years of age (mean age=32.2+/-3.4 years). The control group consisted
      of 129 healthy individuals matched with cases for age and sex, without a family
      history of premature coronary heart disease. G-455A polymorphism of beta
      fibrinogen was tested with polymerase chain reaction and reverse hybridization.
      RESULTS: There was a higher prevalence of carriers of the A allele (GA+AA
      genotype) in controls than in patients (odds ratio [OR] 0.57, 95% confidence
      interval [CI] 0.36 to 0.91, p=0.02). G-455A polymorphism of beta-fibrinogen gene
      was associated with lower risk for acute MI (OR 0.46, 95% CI 0.25 to 0.83,
      p=0.01) after adjusting for major cardiovascular risk factors. Fibrinogen levels
      were higher in patients compared to controls [332 (292-385) vs. 311 (262-373)
      mg/dL, p=0.01], but the adjusted for classical risk factors fibrinogen levels did
      not differ (OR 1.003, 95% CI 0.99 to 1.01, p=0.37). Patients possessing the A
      allele did not differ in their fibrinogen and lipid levels compared to patients
      with the -455GG genotype. CONCLUSIONS: Our data indicate that the presence of the
      G-455A polymorphism of beta-fibrinogen gene has a "protective effect" against the
      development of non-fatal acute MI< or =35 years of age in Greece.

PMID- 19409602
TI  - Re: Immunohistochemical localization of tissue inhibitor of matrix
      metalloproteinase-1 (TIMP-1) in human carious dentine.

PMID- 19409603
TI  - Concurrent blockade of platelet-activating factor and histamine prevents life
      threatening peanut-induced anaphylactic reactions.
AB  - BACKGROUND: Food anaphylaxis is an acute and life-threatening systemic allergic
      reaction. Fatality registries place peanut as the most common culprit of fatal
      and near-fatal reactions in North America. Because prophylaxis and treatment have
      advanced little in recent years, it is imperative to evaluate novel therapies.
      OBJECTIVE: To investigate the impact of blocking mast cell mediators in a mouse
      model of peanut-induced anaphylaxis. METHODS: Mice were sensitized with peanut
      protein and cholera toxin via oral gavage weekly for 4 weeks. One week after the
      last sensitization, separate groups of mice were treated with either a (1) 5
      lypoxygenase inhibitor, (2) a platelet-activating factor (PAF) receptor
      antagonist, (3) histamine receptor antagonists, or (4) a PAF receptor antagonist
      along with histamine receptor antagonists before peanut challenge. RESULTS:
      Treatment targeting either leukotrienes or histamine alone had no beneficial
      effects. In contrast, PAF antagonism significantly attenuated the magnitude and
      duration of the anaphylactic reactions. Particularly, it prevented severe
      reactions. Moreover, 83% of PAF-treated versus 43% of untreated mice reached
      recovery within 120 minutes after peanut challenge. Notably, combined blockade of
      PAF and histamine had a clearly greater beneficial effect. In fact, all but 1
      mouse developed mild, if any, anaphylactic reactions. In addition, combination
      therapy was associated with a significant decrease in vascular leakage and
      release of vasoactive mediators after peanut challenge. CONCLUSION: Combination
      therapy blocking both PAF and histamine markedly reduces the severity of peanut
      induced anaphylaxis, and thus it may be a potential life-saving therapeutic
      approach in peanut and, likely, other food-induced anaphylaxis.

PMID- 19409604
TI  - Higher serum folate levels are associated with a lower risk of atopy and wheeze.
AB  - BACKGROUND: Folic acid is known to be associated with inflammatory diseases, but
      the relationship between folic acid and allergic diseases is unclear. OBJECTIVES:
      The purpose of the study was to examine the relationship between serum folate
      levels and markers of atopy, wheeze, and asthma. METHODS: Data were obtained from
      the 2005-2006 National Health and Nutrition Examination Survey in which serum
      folate and total IgE levels were measured in 8083 subjects 2 years of age and
      older. A high total IgE level was defined as greater than 100 kU/L. Allergen
      specific IgE levels were measured for a panel of 5 common aeroallergens. Atopy
      was defined as at least 1 positive allergen-specific IgE level. Doctor-diagnosed
      asthma and wheeze in the previous 12 months were assessed by means of
      questionnaire. RESULTS: Serum folate levels were inversely associated with total
      IgE levels (P < .001). The odds of a high total IgE level, atopy, and wheeze
      decreased across quintiles of serum folate levels, indicating a dose-response
      relationship between serum folate levels and these outcomes. Each of these
      associations remained statistically significant after adjusting for age, sex,
      race/ethnicity, and poverty index ratio. Adjusted odds ratios associated with the
      fifth quintile of folate relative to the first quintile were as follows: high IgE
      level, 0.70 (95% CI, 0.53-0.92); atopy, 0.69 (95% CI, 0.57-0.85); and wheeze,
      0.60 (95% CI, 0.44-0.82). Higher folate levels were also associated with a lower
      risk of doctor-diagnosed asthma, but this finding was not statistically
      significant (odds ratio for fifth quintile vs first quintile, 0.84 [95% CI, 0.70
      1.02]). CONCLUSIONS: Serum folate levels are inversely associated with high total
      IgE levels, atopy, and wheeze.

PMID- 19409605
TI  - Specific allergic sensitization in parents and their 18-year-old offspring in the
      Suburban Detroit Childhood Allergy Study.
AB  - BACKGROUND: Allergic sensitization is increased among offspring of sensitized
      parents. OBJECTIVE: We sought to evaluate whether 18-year-old offspring are
      likely to have the same allergic sensitizations as their parents. METHODS:
      Eighteen-year-old participants in an unselected birth cohort and their parents
      were tested for total and increased (>0.35 kU/L) levels of allergen-specific IgE
      to 6 allergens: Dermatophagoides farinae, dog, cat, grass, ragweed, and
      Alternaria alternata. RESULTS: In 316 parent-teen triads parental sensitization
      to any of 6 allergens was associated with teen sensitization to any of those same
      allergens. An increased risk of matched sensitization (ie, a teen has an
      increased risk of being sensitized to the same specific allergen as their parent)
      was found after adjusting for the spouse's sensitivities and adjusting for other
      allergens (ie, the parent had an allergic sensitization but not to the particular
      allergen under analysis). Risk of maternal matched sensitization with their teen
      to cat (adjusted odds ratio [aOR], 2.1; 95% CI, 1.0-4.5), grass (aOR, 2.5; 95%
      CI, 1.2-5.2), and A alternata (aOR, 2.4; 95% CI, 1.1-5.5) was increased when
      compared with that seen in teens without parental allergen-specific
      sensitization. Similarly, a higher than expected risk of paternal matched
      sensitization with their teen to dog (aOR, 2.7; 95% CI, 1.3-5.9), D farinae (aOR,
      2.7; 95% CI, 1.4-5.1), and grass (aOR, 2.7; 95% CI, 1.5-5.9) was observed.
      CONCLUSION: Parental allergen-specific IgE increases the likelihood of
      sensitization to the same allergen in young adult offspring.

PMID- 19409607
TI  - MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human
      embryonic stem cells.
AB  - MicroRNAs (miRNAs) are posttranscriptional modulators of gene expression and play
      an important role in many developmental processes. We report here that expression
      of microRNA-145 (miR-145) is low in self-renewing human embryonic stem cells
      (hESCs) but highly upregulated during differentiation. We identify the
      pluripotency factors OCT4, SOX2, and KLF4 as direct targets of miR-145 and show
      that endogenous miR-145 represses the 3' untranslated regions of OCT4, SOX2, and
      KLF4. Increased miR-145 expression inhibits hESC self-renewal, represses
      expression of pluripotency genes, and induces lineage-restricted differentiation.
      Loss of miR-145 impairs differentiation and elevates OCT4, SOX2, and KLF4.
      Furthermore, we find that the miR-145 promoter is bound and repressed by OCT4 in
      hESCs. This work reveals a direct link between the core reprogramming factors and
      miR-145 and uncovers a double-negative feedback loop involving OCT4, SOX2, KLF4,
      and miR-145.

PMID- 19409608
TI  - A UK Google for guidelines.

PMID- 19409606
TI  - Overweight and changes in weight status during childhood in relation to asthma
      symptoms at 8 years of age.
AB  - BACKGROUND: Asthma may be more prevalent in overweight children. However, how
      early overweight and changes in weight status during childhood affect the asthma
      risk is unclear. OBJECTIVES: To investigate overweight and changes in overweight
      status in children age 1 to 8 years in relation to asthma symptoms in childhood.
      METHODS: We studied 3756 children who participated in a large birth cohort study.
      The parents reported their children's weight and height, and wheeze, dyspnea, and
      prescription of inhaled corticosteroids in yearly questionnaires. Sensitization
      to inhalant allergens and bronchial hyperresponsiveness (BHR) were determined at
      8 years. RESULTS: At 8 years, 275 children (7.3%) wheezed, 361 (9.6%) had
      dyspnea, and 268 (7.1%) had a prescription of inhaled corticosteroids in the
      preceding year. Children who had a persistent high body mass index (BMI,
      weight/height2) during childhood or a high BMI at 6 to 7 years had a
      significantly increased risk of dyspnea (adjusted odds ratio, 1.68; 95% CI, 1.18
      2.39, for a high BMI at 6-7 years) and measured BHR (adjusted odds ratio, 1.66;
      95% CI, 1.10-2.52) at 8 years. Children with a high BMI at a young age, but who
      developed a normal BMI at 6 to 7 years, did not have an increased risk of dyspnea
      or BHR at 8 years. BMI was not associated with sensitization. CONCLUSION:
      Children with a current high BMI are at increased risk to have dyspnea and BHR at
      8 years. A high BMI at an earlier age is not related to an increased risk if the
      child has become normal weight at 6 to 7 years.

PMID- 19409609
TI  - NHS Evidence: better and faster access to information.

PMID- 19409610
TI  - The robustness of ecological indicators to detect long-term changes in the
      macrobenthos of estuarine systems.
AB  - Accurate and reliable benthic quality indicators are in great demand following
      the recent developments and the strict time schedule for implementing the
      European Water Framework Directive. The Mondego estuary has experienced a
      progressive deterioration during the 1990s, followed by a partial ecological
      recovery due to restoration measures in 1997/1998. We have used the estuary as a
      model system to test the performance and robustness of a set of ecological
      indicators in highlighting the changes in the ecological state of intertidal
      areas. Over a period of 17 years (1985-2002), we calculated Margalef, Shannon
      Wiener, Berger-Parker, Taxonomic Distinctness measures, AZTI's Marine Biotic
      Index, Infaunal Trophic Index, and Eco-Exergy based indices and tested
      differences across periods characterised by different anthropogenic disturbance.
      We combined temporal data within three periods: before, during and after
      disturbance, based on progressive information on the changes in the extended type
      of anthropogenic disturbance. Indices were then compared with biological and
      abiotic descriptors (macroalgae, macrophytes, benthic macrofauna, nutrients
      concentration, sediment grain size and total organic carbon). We found great
      disparity in the indicators ability to capture temporal changes, showing distinct
      performances at each site. At the Zostera noltii site, only Margalef, Total
      Taxonomic Distinctness and the thermodynamically based indices captured temporal
      changes, despite giving higher values during the disturbance period. At the bare
      sediment site, Taxonomic Distinctness, ITI, Shannon-Wiener, Berger-Parker, AMBI
      and the TBI were able to distinguish between periods, in agreement with the
      differences observed analysing the macrobenthic assemblages. Furthermore,
      Taxonomic Distinctness was not robust enough to detect any temporal or spatial
      change. We thus suggest further research to understand the behaviour of
      ecological indicators, in view of their crucial importance for the management and
      protection of marine coastal areas.

PMID- 19409611
TI  - In vivo evaluation of vaginal films for mucosal delivery of nitric oxide.
AB  - Nitric oxide (NO)-releasing vaginal films were developed and evaluated as a
      potential advanced treatment option for female sexual arousal disorder (FSAD).
      The polymeric films containing s-nitrosoglutathione (GSNO), an endogenous NO
      donor, were prepared using the reduced-pressure drying method. The surface
      morphology, thermal/mechanical properties, stability, loading efficiency and
      physicodynamic properties were characterized and the pharmacological activities
      were evaluated through in vitro and in vivo studies. The GSNO films were
      homogeneous and transparent, and showed suitable mucoadhesiveness and mechanical
      properties. The release profiles of NO from the GSNO films followed the first
      order kinetic pattern and NO activated the NO-cGMP signaling pathway in vaginal
      cells. The GSNO films significantly enhanced the duration of action of GSNO and
      vagina blood perfusion in the rat model without causing any cytotoxic effects.
      The NO-releasing vaginal films might be used as a promising treatment device
      against FSAD.

PMID- 19409612
TI  - Stimulation of glutamate receptors in cultured hippocampal neurons causes Ca2+
      dependent mitochondrial contraction.
AB  - Cultured hippocampal neurons expressing mitochondrially-targeted enhanced yellow
      fluorescent protein (mito-eYFP) were used to quantitatively examine mitochondrial
      remodelling in response to excitotoxic glutamate. Mitochondrial morphology was
      evaluated using laser spinning-disk confocal microscopy followed by calibrated
      image processing and 3D image rendering. Glutamate triggered an increase in
      cytosolic Ca(2+) and mitochondrial depolarization accompanied by Ca(2+)-dependent
      morphological transformation of neuronal mitochondria from "thread-like" to
      rounded structures. The quantitative analysis of the mitochondrial remodelling
      revealed that exposure to glutamate resulted in a decrease in mitochondrial
      volume and surface area concurrent with an increase in sphericity of the
      organelles. NIM811, an inhibitor of the mitochondrial permeability transition,
      attenuated the glutamate-induced sustained increase in cytosolic Ca(2+) and
      suppressed mitochondrial remodelling in the majority of affected neurons, but it
      did not rescue mitochondrial membrane potential. Shortening, fragmentation, and
      formation of circular mitochondria with decreased volume and surface area
      accompanied mitochondrial depolarization with FCCP. However, FCCP-induced
      morphological alterations appeared to be distinctly different from mitochondrial
      remodelling caused by glutamate. Moreover, FCCP prevented glutamate-induced
      mitochondrial remodelling suggesting an important role of Ca(2+) influx into
      mitochondria in the morphological alterations. Consistent with this, in saponin
      permeabilized neurons, Ca(2+) caused mitochondrial remodelling which could be
      prevented by Ru(360).

PMID- 19409614
TI  - Physiological and antioxidant responses of Salvinia natans exposed to chromium
      rich wastewater.
AB  - Salvinia natans possess capacity to accumulate high concentrations of chromium
      (Cr). Studies were carried out to evaluate physiological efficiency and defensive
      potential of plant exposed to Cr-rich wastewater. Among photochemical reactions,
      photosystem I (PS I) and photosystem II (PS II) activity noted an increase in
      plants exposed to Cr-rich wastewater. Fluorescence ratio F(v)/F(m) depicted no
      alteration in plants exposed to Cr. The activity of ribulose-1,5-biphosphate
      carboxylase-oxygenase (Rubisco) noted a decline, while transthylakoidal pH
      gradient (DeltapH) (correlative of photophosphorylation) showed increase in
      plants exposed to Cr-rich wastewater. Plants lacked the ability to produce
      malondialdehyde, but possessed efficient enzymic and non-enzymic antioxidant
      defense mechanisms that played important role in curtailing oxidative stress. The
      activities of antioxidant enzymes showed alleviation in plants exposed to Cr-rich
      wastewater. The levels of cellular antioxidants noted decline suggesting a
      defensive role in protection against oxidative stress caused by Cr. The present
      findings suggest that Salvinia possess efficient antioxidant machinery that
      curtails oxidative stress caused by Cr-rich wastewater and protects
      photosynthetic machinery from damage.

PMID- 19409613
TI  - Downregulation of JUNB mRNA expression in advanced phase chronic myelogenous
      leukemia.
AB  - JUNB inactivation in transgenic mice results in a myeloproliferative disorder
      that closely resembles human chronic myelogenous leukemia (CML). It has been
      reported that downregulation of JUNB expression is a universal phenomenon in
      patients with CML due aberrant DNA methylation of its promoter. Based on this, we
      studied methylation and gene expression levels of JUNB in CML. We analyzed the
      methylation status of the JUNB gene in 6 cell lines and in 102 patients with CML
      using several bisulfite PCR assays. JUNB expression was analyzed using real-time
      PCR and gene expression profiling. JUNB methylation was not observed in any of
      the cell lines studied, and only in 3% of patients with CML. Despite the lack of
      JUNB methylation, JUNB was expressed at low levels both in CML cell lines (median
      dCT -6.86; range -5.87 to -9.61), and in patients with CML in blastic phase (BP)
      (median dCT -3.95; range -1.48 to -6.29) (p = 0.002). Finally, we evaluated JUNB
      expression in 82 additional patients with CML by gene expression arrays. We found
      that JUNB was significantly downregulated in advanced phase CML in contrast to
      chronic phase CML (median log ratio difference in expression = 0.53). Overall,
      our results indicate that JUNB expression is downregulated in advanced phase CML
      through a mechanism independent from DNA methylation.

PMID- 19409615
TI  - Psychopathy and instrumental aggression: Evolutionary, neurobiological, and legal
      perspectives.
AB  - In the study of aggression, psychopathy represents a disorder that is of
      particular interest because it often involves aggression which is premeditated,
      emotionless, and instrumental in nature; this is especially true for more serious
      types of offenses. Such instrumental aggression is aimed at achieving a goal
      (e.g., to obtain resources such as money, or to gain status). Unlike the
      primarily reactive aggression observed in other disorders, psychopaths appear to
      engage in aggressive acts for the purpose of benefiting themselves. This is
      especially interesting in light of arguments that psychopathy may represent an
      alternative life-history strategy that is evolutionarily adaptive; behaviors such
      as aggression, risk-taking, manipulation, and promiscuous sexual behavior
      observed in psychopathy may be means by which psychopaths gain advantage over
      others. Recent neurobiological research supports the idea that abnormalities in
      brain regions key to emotion and morality may allow psychopaths to pursue such a
      strategy-psychopaths may not experience the social emotions such as empathy,
      guilt, and remorse that typically discourage instrumentally aggressive acts, and
      may even experience pleasure when committing these acts. Findings from brain
      imaging studies of psychopaths may have important implications for the law.

PMID- 19409616
TI  - Aggression, psychopathy and brain imaging - Review and future recommendations.
AB  - Violent behavior appears to result from a complex web of interacting genetic as
      well as environmental factors. Psychopathy is a strong predictor for relapse in
      violent acts. The current review shed light on rapidly expanding knowledge in
      brain imaging related to violent behavior and psychopathy. A literature search
      was performed in PubMed, Cochrane and PsycInfo combining the key words: mentally
      disordered offender/aggression/violence/ crime/forensic psychiatry/brain imaging
      neuroimaging/fMRI/MRI/PET/SPECT/lack of empathy/psychopathy and antisocial
      personality disorder. The reviewed material, which consisted of 48 articles,
      indicates a rather strong consensus on the connection between dysfunctional parts
      of the frontal and temporal lobes and violent antisocial behavior and
      psychopathy. In future studies, it would be useful to focus on the limbic system
      and to investigate which parts of the frontal lobes and cerebral networks that
      are of interest in the psychopathic personality. Moreover, the reviewed material
      highlights some of the methodological difficulties in this area of research such
      as selection bias in the recruitment of patients, inadequate matching of control
      subjects, and sometimes incongruous results. In the future we hope that brain
      imaging can be used to map biological deviations in different offenders in order
      to try to learn more about the different mechanisms behind violent behaviors.

PMID- 19409617
TI  - Specificity of the zebrafish host transcriptome response to acute and chronic
      mycobacterial infection and the role of innate and adaptive immune components.
AB  - Pathogenic mycobacteria have the ability to survive within macrophages and
      persist inside granulomas. The complex host-pathogen interactions that determine
      the outcome of a mycobacterial infection process result in marked alterations of
      the host gene expression profile. Here we used the zebrafish model to investigate
      the specificity of the host response to infections with two mycobacterium strains
      that give distinct disease outcomes: an acute disease with early lethality or a
      chronic disease with granuloma formation, caused by Mycobacterium marinum strains
      Mma20 and E11, respectively. We performed a microarray study of different stages
      of disease progression in adult zebrafish and found that the acute and the
      chronic strains evoked partially overlapping host transcriptome signatures,
      despite that they induce profoundly different disease phenotypes. Both strains
      affected many signaling cascades, including WNT and TLR pathways. Interestingly,
      the strongest differences were observed at the initial stage of the disease. The
      immediate response to the acute strain was characterized by higher expression of
      genes encoding MHC class I proteins, matrix metalloproteinases, transcription
      factors, cytokines and other common immune response proteins. In contrast, small
      GTPase and histone gene groups showed higher expression in response to the
      chronic strain. We also found that nearly 1000 mycobacterium-responsive genes
      overlapped between the expression signatures of infected zebrafish adults and
      embryos at different stages of granuloma formation. Since adult zebrafish possess
      an adaptive immune system similar to mammals and zebrafish embryos rely solely on
      innate immunity, this overlap indicates a major contribution of the innate
      component of the immune system in the response to mycobacterial infection. Taken
      together, our comparison of the transcriptome responses involved in acute versus
      chronic infections and in the embryonic versus adult situation provides important
      new leads for investigating the mechanism of mycobacterial pathogenesis.

PMID- 19409618
TI  - A method for eliciting scale errors in preschool classrooms.
AB  - Six preschool classrooms, containing children between the ages of 4.0 and 40.0
      months, were seeded with miniature items to examine how easily scale errors could
      be elicited. Observations occurred over a period of 3 months, with a total of 280
      min of observations per classroom. A concealed observer documented all
      interactions with the miniature items. A total of 93 scale errors occurred, with
      a higher frequency committed by the younger children. These results confirm
      findings from previous research and suggest that scale errors can be effectively
      elicited in a preschool classroom. Our approach may provide a useful method for
      systematically studying the factors that influence scale errors.

PMID- 19409619
TI  - Effect of aspirin treatment on TNFalpha production by women with a history of
      preterm birth.
AB  - Lipopolysaccharide (LPS)-stimulated TNFalpha production is reported to be greater
      for whole blood (WB) cultures prepared from patients with a history of preterm
      birth than cultures obtained from women with a history of term birth. The
      objectives of this study were (1) to determine if there is a similar differential
      responsiveness for peripheral blood mononuclear leukocytes (PBML) and (2) to
      determine if treatment with aspirin influences LPS-stimulated TNFalpha production
      in these patients. WB and PBML were obtained from women with a history of preterm
      delivery before 32 weeks (cases; n=5) and age- and race-matched controls (n=5)
      with a history of uncomplicated term delivery. WB and PBML were cultured and
      stimulated with LPS. All participants then took aspirin daily for 1 week and
      responsiveness of PBML and WB cultures to LPS was retested. The history of
      preterm labor was found to have no effect on LPS-stimulated TNFalpha production
      in cultures of WB or PBML. Aspirin treatment enhanced LPS-stimulated TNFalpha
      production by PBML from controls but not cases. We conclude that endotoxin
      responsiveness of women with a history of preterm birth is similar to that of
      women with a history of term birth in terms of in vitro TNFalpha production.
      Aspirin increases TNFalpha production by PBML in control women but not in women
      with a history of preterm birth. The divergent responses to aspirin treatment in
      patients with and without prior preterm labor may reflect differential regulation
      of cytokine production by prostaglandins in women with preterm labor associated
      with infection or inflammation.

PMID- 19409620
TI  - Immunoglobulin joining (J) chain and its expression in the Chinese soft-shelled
      turtle (Pelodiscus sinensis).
AB  - The immunoglobulin (Ig) joining (J) chain plays an important role in the
      formation of polymeric Igs and their transport into secretions. In the present
      study, the cDNA sequence of J chain has been cloned from the Chinese soft-shelled
      turtle (Pelodiscus sinensis) by reverse transcription (RT)-PCR and rapid
      amplification of cDNA ends (RACE). The cDNA sequence is 2347 bp in length and
      contains an open reading frame of 480 bp encoding 160 aa including the signal
      sequence. The deduced amino acid sequence has a high degree of homology with that
      of an already reported turtle J chain (80.7%), and of chicken (71.3%). By using
      real-time quantitative RT-PCR analysis, a significant up-regulation of J-chain
      transcripts was observed in spleen, kidney and blood of turtles injected with
      inactivated Aeromonas hydrophila, indicating the immune role of J chain in
      response to bacterial infection.

PMID- 19409621
TI  - Role of nitric oxide production in dairy cows naturally infected with
      Mycobacterium avium subsp. paratuberculosis.
AB  - Nitric oxide (NO) is a crucial mediator in host defense and is one of the major
      killing mechanisms within macrophages. Its induction is highly affected by the
      types of cytokines and the infectious agents present. In the current study, NO
      production was evaluated after in vitro infection of unfractionated peripheral
      blood mononuclear cells (PBMCs) with Mycobacterium avium subsp. paratuberculosis
      (MAP) after 8h, 3 and 6 days of culture for cows in different stages of disease.
      In addition, the effects of in vitro exposure to inhibitory cytokines such as
      interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta) as well as
      the pro-inflammatory cytokine IFN-gamma were correlated with the level of NO
      production. Nitric oxide production was consistently higher in cell cultures from
      subclinically infected animals at all time points. An upregulation of NO
      production was demonstrated in unfractionated cell cultures from healthy control
      cows after exposure to MAP infection as compared to noninfected cell cultures. A
      similar increase in NO due to the addition of MAP to cell cultures was also noted
      for clinically infected cows. NO level among subclinically infected cattle was
      greater at all time points tested and was further boosted with the combination of
      both in vitro MAP infection and IFN-gamma stimulation. Alternatively, nonspecific
      stimulation with LPS from Escherichia coli O111:B4-W resulted in an upregulation
      of NO production in all infected groups at 3 and 6 days after in vitro infection.
      Finally, the in vitro exposure to inhibitory cytokines such as IL-10 and TGF-beta
      prior to MAP infection or LPS stimulation resulted in the downregulation of this
      inflammatory mediator (NO) in all experimental groups at all time points. In
      summary, a higher level of NO production was associated with cows in the
      subclinical stage of MAP infection. As well, the results demonstrated an increase
      in NO production upon infection with MAP and in the presence of exogenous IFN
      gamma. Finally, the results suggest an important role of IL-10 and TGF-beta on
      the profile of NO production which may explain the low NO production in MAP
      clinically infected cows.

PMID- 19409622
TI  - Molecular cloning of canine interleukin-31 and its expression in various tissues.
AB  - The newly discovered cytokine, interleukin-31 (IL-31), belongs to the short-chain
      cytokine group. It was reported that transgenic expression of IL-31-induced
      pruritus, similar to atopic dermatitis, in mice, further, excessive amounts of IL
      31 was also expressed in the skin from human patients with atopic dermatitis as
      compared to that from normal people. In this study, canine IL-31 was molecularly
      cloned from concanavalin A-stimulated canine peripheral blood mononuclear cells
      (PBMCs), and its nucleotide sequence was determined. Canine IL-31 contains 4
      alpha-helix structures characteristic of the IL-31 family, and the amino acid
      identity of canine IL-31 with those of human or mouse is 54% and 28%,
      respectively. Furthermore, we detected low levels of canine IL-31 in the thymus,
      testis, spleen, and kidneys, but not in the skin of atopic dogs.

PMID- 19409623
TI  - Prevalence of auditory neuropathy (AN) among infants and young children with
      severe to profound hearing loss.
AB  - Auditory neuropathy is a challenging disorder and needs special
      habilitative/rehabilitative approach. This study aimed to detect its prevalence
      among infants and young children with severe to profound hearing loss. 112
      infants and young children with age ranged 6-32 months were examined and
      diagnosed as having severe to profound hearing loss and were referred for hearing
      aid fitting. Those infants were reassessed in our centers for detecting cases
      with auditory neuropathy. The study group was subjected to immittancemetry,
      behavioral observation audiometry, ABR and cochlear microphonics. RESULTS: 15
      patients were found to have auditory neuropathy according to our criteria for
      diagnosis. CONCLUSIONS: The prevalence of AN in the study group was 13.4%. CM
      were recommended to be tested routinely during ABR assessment whenever abnormal
      results are obtained.

PMID- 19409624
TI  - From high anxiety trait to depression: a neurocognitive hypothesis.
AB  - Although exposure to substantial stress has a major impact on the development of
      depression, there is considerable variability in the susceptibility of
      individuals to the adverse effects of stress. The personality trait of high
      anxiety has been identified as a vulnerability factor to develop depression. We
      propose here a new unifying model based on a series of neurocognitive mechanisms
      (and fed with crucial information provided by research on the fields of emotion,
      stress and cognition) whereby individuals presenting a high anxiety trait are
      particularly vulnerable to develop depression when facing stress and adversity.
      Our model highlights the importance of developing prevention programs addressed
      to restrain, in high anxious individuals, the triggering of a dysfunctional
      neurocognitive cascade while coping with stress.

PMID- 19409626
TI  - Breast cancer in the elderly.
AB  - Breast cancer is the most commonly diagnosed cancer in women and most breast
      cancers are not attributable to risk factors other than female gender and
      increased age. However, despite its increasing prevalence in the geriatric
      population, prospective clinical trials for older cancer patients do not exist
      and most data come from retrospective studies or subanalyses from general
      population studies. As a result physician's, patient's and family members' fear
      predominates and elderly patients do not receive the appropriate treatment when
      compared with younger ones. Treatment is offered according to biological age
      alone and life expectancy, comorbidity and functional status are not considered
      when deciding treatment strategy. Surgery is often denied to patients older than
      70 years of age, radiotherapy and chemotherapy are omitted due to the fear of
      toxicity and hormonal therapy, even though it represents a great tool as adjuvant
      therapy, it is associated with significant morbidity when chosen as primary
      treatment. Palliation of symptoms remains the main goal for metastatic disease
      but for the rest of the patients improving disease-free survival in the early
      stages should guide therapy no matter chronological age.

PMID- 19409625
TI  - Modeling cognitive endophenotypes of schizophrenia in mice.
AB  - Schizophrenia is a complex mental disorder that is still characterized by its
      symptoms rather than by biological markers because we have only a limited
      knowledge of its underlying molecular basis. In the past two decades, however,
      technical advances in genetics and brain imaging have provided new insights into
      the biology of the disease. Based on these advances we are now in a position to
      develop animal models that can be used to test specific hypotheses of the disease
      and explore mechanisms of pathogenesis. Here, we consider some of the insights
      that have emerged from studying in mice the relationship between defined genetic
      and molecular alterations and the cognitive endophenotypes of schizophrenia.

PMID- 19409627
TI  - Echocardiography with Tissue Doppler Imaging and cardiopulmonary exercise testing
      in patients with heart failure: a correlative and prognostic analysis.
AB  - BACKGROUND: Previous investigations have established the prognostic value of
      variables obtained from both echocardiography with tissue Doppler Imaging (TDI)
      and cardiopulmonary exercise testing (CPX) in patients with heart failure (HF).
      Past prognostic comparisons of variables obtained from these evaluation
      techniques have been limited to the comparison of left ventricular ejection
      fraction (LVEF) vs. peak oxygen consumption (VO2). The present investigation
      undertakes a more thorough correlative and prognostic assessment. METHODS: Two
      hundred and forty-three patients with HF (190 male/53 female, age: 62.2+/-9.7)
      underwent echocardiography with TDI and CPX to determine the following variables:
      1) the ratio between mitral early (E) to mitral annular (E') velocity, 2) LVEF,
      3) LV mass, 4) LV end systolic volume (LVESV), 5) Peak VO2, 6) The minute
      ventilation/carbon dioxide production (VE/VCO2) slope, and 7) Exercise
      oscillatory ventilation (EOV). RESULTS: There were 43 cardiac-related deaths
      during the four-year tracking period. In the multivariate analysis, E/E' was the
      strongest prognostic variable (Chi-square: 46.1, p<0.001). LV mass (Residual chi
      square: 16.8, p<0.001), LVESV (Residual chi-square: 8.0, p=0.005) and the VE/VCO2
      slope (Residual chi-square: 4.6, p=0.03) all added significant predictive value
      and were retained in the regression. CONCLUSIONS: The results of the present
      study indicate several variables obtained from echocardiography with TDI are
      prognostically important in HF. The VE/VCO2 slope, which is one of the strongest
      prognostic markers obtained from CPX, adds prognostic value to these variables. A
      combined analysis of both noninvasive techniques may improve the prognostic
      characterization of patients with HF.

PMID- 19409629
TI  - Risk factors for lameness in cubicle housed Austrian Simmental dairy cows.
AB  - Austrian dairy farming is characterised by predominant use of Simmental cows on
      small-scale farms. Our aim was to identify lameness risk factors related to
      housing and management in cubicle housed Austrian dairy cows. Furthermore, we
      used animal-based parameters (ABP) as integrated measures of cubicle quality and
      feeding management. The first author visited 30 farms in eastern Austria with 24
      54 cows (mean=35) in the milking herd during winter housing period, and collected
      data on housing, management, behaviour, and lameness via direct observations and
      an interview (part of Welfare Quality project). Mean lameness prevalence was 31%
      (range 6-70%). Data were analysed using logistic regression with generalised
      estimating equations (GEE). The final model was based on 832 cows and included
      six risk variables, five ABP, and the significant confounders 'county' and
      'lactation number'. Odds for lameness increased with decreasing lying comfort,
      except for cubicle width. The following lying-related factors were significant in
      the final model (odds ratios (OR) in brackets): mats/mattresses as opposed to
      deep bedded cubicle base (1.61), length of lying area (OR 186-191 vs. <178
      cm=0.72) and cubicle width (1.18). Lying-related ABP included abnormal lying
      behaviour (1.36), cow comfort index (0.76), and duration of rising (2.17). Other
      significant housing and management characteristics included slatted flooring
      (1.31), herd size (0.63), and no access to an outdoor loafing area (0.57).
      Regarding metabolic parameters, cows with a body condition score >3.5 had at
      least 0.39 lower odds of being lame, while cows with suboptimal milk protein
      content (<3.2% or >3.8%) had 1.37 times higher odds. Odds for lameness clearly
      increased with age (OR lactation > or =4 vs. 1=3.38). In sum, lying comfort and
      nutrition are key areas for lameness prevention on modern dairy farms in Austria
      with herd sizes above 30 cows.

PMID- 19409628
TI  - Postconditioning during primary percutaneous coronary intervention: a review and
      meta-analysis.
AB  - BACKGROUND: Myocardial postconditioning (POC), defined as intermittent
      interruptions of blood flow at the onset of reperfusion after sustained ischemia,
      may attenuate reperfusion injury. In order to weigh the current evidence linking
      POC to reduction of myocardial infarct size in patients with ST-segment elevation
      myocardial infarction (STEMI) undergoing primary percutaneous coronary
      intervention (pPCI), we performed a systematic review and meta-analysis of the
      available data from small randomised trials. METHODS: A Web-based search was
      performed for relevant studies, and retrieved data were subjected to systematic
      review and meta-analysis. RESULTS: Six studies were identified and the meta
      analysis included a total of 244 patients with STEMI undergoing pPCI with or
      without POC. Pooled analysis of all studies demonstrated a significant reduction
      of peak creatine kinase with POC relative to standard care (weighted mean peak
      creatine kinase difference -609.59 IU/L, 95% confidence interval [CI] -1030 to 
      189; p=0.005). A secondary analysis of 4 of the studies also showed an
      improvement of left ventricular ejection fraction with POC (weighted mean
      ejection fraction difference 4.2%, 95% CI 2.1% to 6.2%; p=0.0001). CONCLUSION:
      This first systematic review and meta-analysis of randomized trials of POC in
      patients with STEMI undergoing primary PCI, demonstrated a significant benefit of
      POC over standard care for reduction of myocardial infarct size as determined by
      peak creatine kinase release and left ventricular ejection fraction. The effects
      of POC on clinical outcomes remain to be determined.

PMID- 19409630
TI  - Dynamics of somatic cell counts and intramammary infections across the dry
      period.
AB  - The objectives of this research were to study the relationship between somatic
      cell count (SCC) and intramammary infection (IMI) across the dry period and the
      risk of subclinical mastitis at the first dairy herd improvement (DHI) test of
      the subsequent lactation. A secondary objective was to determine SCC test
      characteristics for diagnosis of IMI at both the cow and quarter levels. 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, calving and on the day
      of the first DHI test. Somatic cell count status across the dry period was
      defined based on the comparison of quarter SCC from dry-off and the post-calving
      sampling periods and comparison of composite SCC from DHI samples from the last
      test and first test of the following lactation. Of new IMI detected from post
      calving milk samples (n=45), 46.7, 26.7 and 11% were caused by CNS, Streptococci
      and Gram-negative bacteria, respectively. Of cured IMI at post-calving (n=91),
      61.5, 23.1 and 9.9% had CNS, Streptococci and Coryneforms isolated from dry-off
      milk samples. The most frequent microorganisms related to cured IMI were CNS
      (33%). Of chronically infected quarters across the dry period (n=10), only one
      had the same species of pathogen isolated from dry-off and post-calving samples.
      The sensitivity of a SCC threshold of 200,000 cells/mL for detection of
      subclinical IMI was 0.64, 0.69 and 0.65 for milk samples obtained at dry-off,
      post-calving and first DHI test, respectively. The specificity was 0.66, 0.84 and
      0.93 for milk samples obtained at dry-off, post-calving and first DHI test,
      respectively. Quarters with SCC> or =200,000 cells/mL at both dry-off and post
      calving sampling periods were 20.4 times more likely to be subclinically infected
      by a major pathogen (rather than being uninfected) and 5.6 times more likely to
      be subclinically infected by a minor pathogen (rather than being uninfected) at
      the first DHI test than quarters with SCC<200,000 cells/mL at both periods. Cows
      with SCC greater than 200,000 cells/mL at both the last and the first DHI test
      between lactations produced 9.1 kg less milk on the first DHI test day than the
      average milk production of cows with SCC less than 200,000 cells/mL at both
      periods.

PMID- 19409631
TI  - Can a single indicator measure both attainment and shortfall inequality?
AB  - When a distribution can be described either in terms of attainment or in terms of
      shortfall, the classical inequality measures appear to be one-sided. I show that
      it is possible to find indicators which simultaneously measure attainment and
      shortfall inequality. I derive one indicator belonging to the Gini family, and
      another belonging to Coefficient of Variation family. I also indicate how they
      are connected to other measures.

PMID- 19409632
TI  - Marine biominerals: perspectives and challenges for polymetallic nodules and
      crusts.
AB  - Deep sea minerals in polymetallic nodules, crusts and hydrothermal vents are not
      only formed by mineralization but also by biologically driven processes involving
      microorganisms (biomineralization). Within the nodules, free-living and biofilm
      forming bacteria provide the matrix for manganese deposition, and in cobalt-rich
      crusts, coccolithophores represent the dominant organisms that act as bio-seeds
      for an initial manganese deposition. These (bio)minerals are economically
      important: manganese is an important alloying component and cobalt forms part of
      special steels in addition to being used, along with other rare metals, in plasma
      screens, hard-disk magnets and hybrid car motors. Recent progress in our
      understanding of the participation of the organic matrices in the enrichment of
      these metals might provide the basis for feasibility studies of biotechnological
      applications.

PMID- 19409633
TI  - Synthetic gene networks: the next wave in biotechnology?
AB  - Engineering novel, reusable gene networks to provide greater control over
      cellular processes is one of the goals of the emerging discipline of synthetic
      biology. This article reviews the landmark literature pertaining to the
      development of synthetic gene networks, the engineering framework used to design
      and characterize them and the technological developments on the horizon that
      could potentially advance the field in new directions. As gene network
      engineering enters its second decade, an attempt is also made to outline the
      challenges in advancing this nascent field, especially with regard to the
      practical limitations of component reusability and reliability and the
      opportunities that present themselves in the development of novel gene expression
      controllers and single-cell biosensors.

PMID- 19409635
TI  - A cost-outcome analysis of Image-Guided Patient Repositioning in the radiation
      treatment of cancer of the prostate.
AB  - BACKGROUND AND PURPOSE: With Image-Guided Radiation Therapy (IGRT) rapidly
      gaining acceptance in the clinic it is timely to commence an assessment of its
      potential outcome benefit versus costs. MATERIALS AND METHODS: Using Activity
      Based Costing we have calculated the incremental cost of adding Image-Guided
      Patient Repositioning (IGPR), a significant component of IGRT, to both Intensity
      Modulated Radiation Therapy (IMRT) and Three-Dimensional Conformal Radiation
      Therapy (3DCRT) for prostate cancer. The dosimetric outcome benefit resulting
      from the implementation of IGPR is estimated from a publication describing the
      improvement in set-up accuracy using each of four correction protocols. In our
      study outcome is quantified using a metric based on the Equivalent Uniform Dose.
      Our discussion is limited to image-guided corrective translations of the patient
      and does not specifically address margin reduction, rotations, organ deformation
      or major equipment failure modes, all of which are significant additional
      justifications for implementing an IGRT program. RESULTS: Image guidance used
      solely for translational patient repositioning for prostate cancer adds costs
      with relatively little improvement in dosimetric quality. Full exploitation of
      the potential of IGRT, particularly through margin reduction, can be expected to
      result in a reduction in the cost-outcome ratios reported here. CONCLUSIONS: IMRT
      benefits more than 3DCRT from IGPR with the Weekly Shrinking Action Level
      approach yielding the lowest cost-outcome ratio.

PMID- 19409636
TI  - Linac-based or robotic image-guided stereotactic radiotherapy for isolated lymph
      node recurrent prostate cancer.
AB  - We report on 14 patients treated with linac- or robotic image-guided stereotactic
      radiotherapy for isolated lymph node recurrence from prostate cancer, up to the
      mean dose of 30Gy/3 fractions. At the mean follow-up of 18.6months, five patients
      experienced clinical out-field progression. Toxicity was minimal. Further
      investigation is warranted in order to identify the patients that benefit most
      from this treatment modality and to define the optimal association of such local
      approach with androgen deprivation. Hopefully, effective local therapy might
      reduce the burden of systemic therapies given to the recurrent/metastatic
      prostate cancer patients.

PMID- 19409634
TI  - Convergence of biomarkers, bioinformatics and nanotechnology for individualized
      cancer treatment.
AB  - Recent advances in biomarker discovery, biocomputing and nanotechnology have
      raised new opportunities in the emerging fields of personalized medicine (in
      which disease detection, diagnosis and therapy are tailored to each individual's
      molecular profile) and predictive medicine (in which genetic and molecular
      information is used to predict disease development, progression and clinical
      outcome). Here, we discuss advanced biocomputing tools for cancer biomarker
      discovery and multiplexed nanoparticle probes for cancer biomarker profiling, in
      addition to the prospects for and challenges involved in correlating biomolecular
      signatures with clinical outcome. This bio-nano-info convergence holds great
      promise for molecular diagnosis and individualized therapy of cancer and other
      human diseases.

PMID- 19409637
TI  - Mathematical estimation and in vivo dose measurement for cone-beam computed
      tomography on prostate cancer patients.
AB  - BACKGROUND AND PURPOSE: Cone-beam computed tomography (CBCT) increases the doses
      on normal tissues. Our study sought to develop a mathematical model that would
      provide an estimate of and verify in vivo rectal dose from CBCT in prostate
      cancer patients. MATERIALS AND METHODS: Thermoluminescent dosimeters (TLDs) and
      Rando phantoms were used to measure doses to the pelvic region. We used an
      endorectal balloon to measure rectal doses for 10 prostate cancer patients who
      underwent radiotherapy and for whom we were able to acquire CBCT images. A solid
      water phantom and TLDs were used to correlate the rectal doses with body
      thickness/widths. A mathematical method was established to simulate the dose to
      which the patient is exposed during CBCT for the determined body parameters. The
      estimated doses were compared with the measured doses to determine the
      effectiveness of the model. RESULTS: The average measured rectal dose from CBCT
      was 2.8+/-0.3 cGy. The mathematical method was able to predict the rectal dose,
      with the limits of agreement of -0.03+/-0.18 cGy. The average difference between
      predictions and measurements was -1.1+/-3.6%. CONCLUSION: Our mathematical model
      was effective in estimating the exposed dose from CBCT.

PMID- 19409638
TI  - Short-course radiotherapy, with elective delay prior to surgery, in patients with
      unresectable rectal cancer who have poor performance status or significant co
      morbidity.
AB  - BACKGROUND AND PURPOSE: Standard treatment for rectal cancer which threatens the
      expected plane of resection on MRI imaging is long-course, pre-operative
      chemoradiotherapy (1.8-2Gy, 25-28 fractions). Not all patients are suitable for
      this because of age, poor performance status or co-morbidities. We describe our
      experience of short-course (5x5Gy) pre-operative radiotherapy with planned,
      delayed surgery (SCPRT-delay) in this patient group. MATERIALS AND METHODS:
      Between April 2001 and October 2007, 43 patients were selected for SCPRT-delay.
      The clinical records were retrospectively evaluated. RESULTS: Median age was 82
      (range 58-87). Forty-one patients had radiotherapy of which 26 (61%) were
      subsequently able to have surgery. Of these, R0, R1 and R2 resections were
      performed in 22, 2 and 2 patients, respectively. Treatment was well tolerated,
      although two patients required hospital admission for management of diarrhoea and
      one developed significant late small bowel toxicity, attributable to
      radiotherapy. In those undergoing R0 or R1 resection there have been no local
      recurrences (median follow-up 18 months). Median survival for the whole group was
      23 months, although this was 44 months in those undergoing surgery. CONCLUSIONS:
      SCPRT-delay appears to be a useful alternative to long-course pre-operative
      chemoradiotherapy in this high-risk group of patients.

PMID- 19409641
TI  - A Bayesian network model for the diagnosis of the caring procedure for wheelchair
      users with spinal injury.
AB  - This paper describes a probabilistic causal model for the caring procedure to be
      followed on wheelchair users with spinal injury. Due to loss of sensation and
      movement caused by spinal cord injuries, the information extracted about patient
      findings (i.e. the signs and symptoms) can often be incomplete. This, in turn,
      introduces uncertainty in assessing the existence and severity of a given
      condition-and thus, employment of the appropriate caring procedure. Bayesian
      networks are a framework that enables probabilistic inference; therefore, they
      are useful for diagnostic reasoning and selection of the appropriate caring
      procedure in the face of uncertainty. The network structure and numerical
      parameters are based on data elicited from the qualified staff nurses and
      available literature of the National Spinal Injury Centre, Stoke Mandeville
      Hospital, Aylesbury, UK, as well as the compiled knowledge base within the
      DIMITRA rule-based expert system [M. Athanasiou, J.Y. Clark, DIMITRA: an online
      expert system for carers of paraplegics and quadriplegics, International Journal
      of Healthcare Technology and Management 7(5) (2006) 44-451]. We also present the
      model and report the results of the diagnostic performance tests using the
      AgenaRiskn [Agena Limited, AgenaRisk Software Package, http://www.agena.co.uk]
      Bayesian network package.

PMID- 19409640
TI  - The prevalence of 6 weeks postpartum abnormal glucose tolerance in Caucasian
      women with gestational diabetes.
AB  - AIMS: To evaluate the incidence of impaired glucose tolerance (IGT), impaired
      fasting glucose (IFG) and diabetes in 318 Caucasian women with gestational
      diabetes (GDM) at 6 weeks postpartum. METHODS: All women had 75g OGTT and the
      following data were collected: age, height, weight, results of the challenge 50g
      and diagnostic 75g OGTT, and glycated hemoglobin (HbA1c). RESULTS: 13.5% of women
      had abnormal glucose tolerance, including 1.3% of diabetes, 2.5% of IFG and 7.5%
      of IGT. None of the prepregnancy independent variables, such as age, body mass
      index, prior GDM, prior macrosomia, family history of type 2 diabetes and
      multiparity was a predictor for the abnormal OGTT. In contrast, pregnancy-related
      risk factors, like gestational week at GDM diagnosis (P=0.001), glucose values in
      the challenge (P=0.007) and diagnostic (P=0.02) OGTTs and HbA1c (P=0.01) were
      significantly associated with the persistence of glucose intolerance after
      delivery. CONCLUSION: The incidence of postpartum abnormal glucose tolerance in
      Caucasian women with GDM was 13.5% and was associated with an early diagnosis of
      GDM, severity of hyperglycemia and requirement for insulin therapy. The diagnosis
      of GDM should initiate a lifelong monitoring of glucose tolerance to minimize the
      risk of developing overt diabetes.

PMID- 19409639
TI  - Triple angiokinase inhibition, tumour hypoxia and radiation response of FaDu
      human squamous cell carcinomas.
AB  - BACKGROUND AND PURPOSE: To test the effect of BIBF 1120, a novel small molecule
      inhibitor of multiple angiogenic receptor tyrosine kinases, on the hypoxia and
      radiation response of tumours. MATERIALS AND METHODS: Poorly differentiated human
      squamous cell carcinoma FaDu growing in nude mice was treated with BIBF 1120 and
      investigated by functional histology. To test the effect of BIBF 1120 on the
      radiobiological hypoxic fraction (rHF), the number and intrinsic radiation
      sensitivity of tumour stem cells and the outcome after fractionated irradiation,
      a series of local tumour control assays were performed. RESULTS: BIBF 1120
      significantly reduced the vessel area, vessel area with a perfusion signal and
      tumour growth rate but did not affect tumour hypoxia or the number and intrinsic
      radiation sensitivity of tumour stem cells. Concurrent BIBF 1120 had no effect on
      local tumour control after fractionated irradiation. CONCLUSION: Triple
      angiokinase inhibition resulted in a clear-cut decrease of angiogenesis, vessel
      area with a perfusion signal and tumour growth but did not change tumour hypoxia
      or radiation response of tumour stem cells. Further experiments into mechanisms
      of interaction between anti-angiogenic strategies and irradiation appear to be
      necessary to better define and exploit the potential of this strategy to improve
      local tumour control after fractionated radiotherapy.

PMID- 19409642
TI  - Quantitative breath analysis of volatile organic compounds of lung cancer
      patients.
AB  - Due to state-of-art analytical techniques, non-invasive exhaled volatile organic
      compounds (VOCs) analysis has become a potential method for early diagnosis of
      lung cancer. We collected breath samples from 43 patients with non-small cell
      lung cancer (NSCLC) and 41 normal controls using Tedlar gas bags. The VOCs were
      extracted with solid phase micro-extraction (SPME) and analyzed by gas
      chromatography (GC)/mass spectrometry (MS). The number of VOCs detected in each
      breath sample ranged from 68 to 114. Among the VOCs 1-butanol and 3-hydroxy-2
      butanone were found at significantly higher concentrations in breath of the lung
      cancer patients compared to the controls. VOCs levels were not significantly
      different between early stage lung cancer patients and late stage lung cancer
      patients. Lung adenocarcinoma was significantly related to higher VOCs
      concentrations in the breath. Our data showed that 1-butanol and 3-hydroxy-2
      butanone in breath could possibly be taken as useful breath biomarkers for
      discerning potential lung cancer patients and VOCs analysis could be used as a
      complementary test for the diagnosis of lung cancer.

PMID- 19409644
TI  - Efficacy of chemotherapy with carboplatin and paclitaxel for unresectable thymic
      carcinoma.
AB  - BACKGROUND: Thymic carcinoma is a very rarely encountered neoplasm and no optimal
      chemotherapeutic regimen has been established yet. METHODS: The records of
      previously untreated thymic carcinoma patients with unresectable disease who had
      been treated with paclitaxel and carboplatin as first-line chemotherapy between
      2003 and 2008 were reviewed, retrospectively. Paclitaxel was administered at the
      dose of 200mg/m(2) and carboplatin at an AUC of 6 on day 1, with the treatment
      cycle repeated every 3 weeks. RESULTS: Eleven patients were registered, and a
      total of 45 cycles of carboplatin/paclitaxel were administered (median cycles per
      patient, 4; range, 2-6). Although the principal toxicity of this regimen was
      neutropenia, with grade 3 or more severe neutropenia being observed in nine
      patients (82%), there were no cases of febrile neutropenia. There were also no
      cases of grade 3 or more severe peripheral sensory neuropathy. Thus, the toxicity
      profile of the treatment regimen was acceptable. The overall response rate was
      36%, and the median survival time and median progression-free survival were 22.7
      months and 7.9 months, respectively. CONCLUSION: Combined paclitaxel+carboplatin
      therapy exhibits activity and acceptable toxicity in the first-line setting in
      patients with unresectable thymic carcinoma.

PMID- 19409643
TI  - Feasibility study of postoperative adjuvant chemotherapy with S-1 (tegaful,
      gimeracil, oteracil potassium) for non-small cell lung cancer-LOGIK 0601 study.
AB  - INTRODUCTION: The feasibility of using S-1, a novel oral dihydropyrimidine
      dehydrogenase (DPD)-inhibitory 5-fluorouracil, as postoperative adjuvant
      chemotherapy for completely resected non-small cell lung cancer (NSCLC) was
      analyzed. METHODS: Adjuvant chemotherapy consisted of eight courses (2-week
      administration and 1-week withdrawal) of S-1, at 80-120 mg/body per day in an
      outpatient setting. From July 2006 through March 2007, 30 patients were enrolled
      in this multi-institutional trial. RESULTS: The planned eight courses of S-1
      administration were accomplished to 17 patients (56.7%; 95% confidence interval
      37.4-74.5%). Two patients discontinued the treatment due to the disease
      recurrence, and therefore the completion rate was calculated to be 60.7%. The
      completion rate in patients younger than 70 years old was 78.6% while it was
      42.9% in those of 70 years old or older. In seven patients including five elderly
      patients (> or =70 years old), S-1 administration was discontinued due to
      subjective symptoms, such as anorexia, during the early courses. The rate of
      patients with mild renal impairment (60< or =creatinine clearance<80 ml/min)
      tended to be higher in the elderly patients than that in the younger patients.
      Although grade 3 neutropenia (6.7%), anemia (6.7%), thrombocytopenia (3.3%) and
      digestive hemorrhage (3.3%) were observed, no grade 4 adverse events occurred.
      CONCLUSION: Postoperative long-term administration of S-1 seems feasible as
      adjuvant chemotherapy for NSCLC, with few adverse events except for the early
      development of anorexia, especially in the elderly patients.

PMID- 19409645
TI  - Phase II study of ASA404 (vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA)
      1800mg/m(2) combined with carboplatin and paclitaxel in previously untreated
      advanced non-small cell lung cancer.
AB  - This single-arm phase II study evaluated the tumor-vascular disrupting agent
      ASA404 (vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800mg/m(2) plus
      standard therapy of carboplatin and paclitaxel in patients with advanced non
      small cell lung cancer (NSCLC). This ASA404 dose is 50% higher than that used in
      previous phase II studies. Thirty patients with histologically confirmed stage
      IIIb or IV NSCLC previously untreated with chemotherapy received carboplatin AUC
      6mg/mlmin plus paclitaxel 175mg/m(2) plus ASA404 1800mg/m(2) every 21 days for up
      to six cycles. The addition of ASA404 1800mg/m(2) to standard therapy produced
      little change in the systemic exposure of either total or free carboplatin or
      paclitaxel, and was generally well-tolerated, with no cardiac serious adverse
      events or clinically relevant ophthalmic abnormalities. The best overall tumor
      response was partial response, which was seen in 37.9% of patients by independent
      assessment and in 46.7% by investigator assessment. Stable disease was seen in
      48.3% of patients by independent assessment and in 43.3% by investigator
      assessment. Median time to tumor progression was 5.5 months by investigator
      assessment and median survival was 14.9 months. The data from this trial
      corroborate findings from a recent randomized phase II trial, which suggested
      improvements in efficacy variables, including survival, when ASA404 1200mg/m(2)
      was added to standard therapy for advanced NSCLC. The manageable safety profile,
      lack of adverse pharmacokinetic interactions and efficacy outcomes seen in this
      single-arm study suggest that ASA404 1800mg/m(2) is a viable dose for future
      combination studies.

PMID- 19409646
TI  - Alternative mechanisms of range expansion are associated with different changes
      of evolutionary potential.
AB  - Human-induced and natural range expansion of species are expected to lead to
      different patterns of genetic diversity, which might themselves be trait
      dependent. Recent studies examined the molecular and quantitative genetic
      variation following the range expansion of three plant species. The results
      suggest that contrasting diversity patterns among species reflect how range
      expansion has occurred and the level of fragmentation of the original habitat.
      Unexpectedly, even introductions from a homogeneous environment do not preclude a
      species from adapting to a new environment and becoming invasive.

PMID- 19409647
TI  - Adaptive radiation, nonadaptive radiation, ecological speciation and
      nonecological speciation.
AB  - Radiations of ecologically and morphologically differentiated sympatric species
      can exhibit the pattern of a burst of diversification, which might be produced by
      ecological divergence between populations, together with the acquisition of
      reproductive isolation ('ecological speciation'). Here we suggest that this
      pattern could also arise if speciation precedes significant ecological
      differentiation (i.e. through geographical isolation and nonadaptive radiation).
      Subsequently, species ecologically differentiate and spread into sympatry.
      Alternative routes to producing ecologically differentiated sympatric species are
      difficult to detect in old radiations. However, nonadaptive radiations are common
      and might therefore regularly be responsible for currently ecologically
      differentiated sympatric species (e.g. among groups that are not susceptible to
      ecological speciation). Species evolving nonadaptively over long periods might
      eventually replace young, ecologically produced species.

PMID- 19409648
TI  - Adaptive monitoring: a new paradigm for long-term research and monitoring.
AB  - Long-term research and monitoring can provide important ecological insights and
      are crucial for the improved management of ecosystems and natural resources.
      However, many long-term research and monitoring programs are either ineffective
      or fail completely owing to poor planning and/or lack of focus. Here we propose
      the paradigm of adaptive monitoring, which aims to resolve many of the problems
      that have undermined previous attempts to establish long-term research and
      monitoring. This paradigm is driven by tractable questions, rigorous statistical
      design at the outset, a conceptual model of the ecosystem or other entity being
      examined and a human need to know about ecosystem change. An adaptive monitoring
      framework enables monitoring programs to evolve iteratively as new information
      emerges and research questions change.

PMID- 19409649
TI  - Speed-accuracy tradeoffs in animal decision making.
AB  - The traditional emphasis when measuring performance in animal cognition has been
      overwhelmingly on accuracy, independent of decision time. However, more recently,
      it has become clear that tradeoffs exist between decision speed and accuracy in
      many ecologically relevant tasks, for example, prey and predator detection and
      identification; pollinators choosing between flower species; and spatial
      exploration strategies. Obtaining high-quality information often increases
      sampling time, especially under noisy conditions. Here we discuss the mechanisms
      generating such speed-accuracy tradeoffs, their implications for animal decision
      making (including signalling, communication and mate choice) and the significance
      of differences in decision strategies among species, populations and individuals.
      The ecological relevance of such tradeoffs can be better understood by
      considering the neuronal mechanisms underlying decision-making processes.

PMID- 19409650
TI  - Gene flow and species delimitation.
AB  - A defining feature of species is that their constituting populations are
      connected by gene flow. However, interspecific gene flow (introgression) can
      affect species integrity. If some genome components were less prone to
      introgression than others, they should be particularly suitable to delimitate
      species. Recent simulation studies have predicted a negative correlation between
      intra- and interspecific gene flow, suggesting that markers associated with the
      most dispersing sex should better delimitate species. A review of studies of
      introgression in species with sex-biased dispersal largely confirms this
      prediction. Hence, species delimitation should be more effective with markers
      experiencing high levels of gene flow, a simple but not widely appreciated
      prediction.

PMID- 19409652
TI  - Focusing the metaphor: plant root foraging behaviour.
AB  - Many authors assert that plants exhibit complex behaviours which are analogous to
      animal behaviour. However, plant ecologists rarely root these studies in a
      conceptual foundation as fertile as that used by animal behaviourists. Here we
      adapt the optimality principles that facilitated numerous advances in the study
      of animal foraging behaviour to create one possible framework for plant foraging
      behaviour. Following the traditions of animal foraging ecology, we discuss issues
      of search and handling in relation to plant root foraging. We also develop a
      basic plant-centered model that incorporates modular growth and foraging
      currencies relevant to plant growth. We conclude by demonstrating how this new
      foundation could be adapted to address five fundamental questions in plant
      foraging ecology.

PMID- 19409651
TI  - Kin competition and the evolution of cooperation.
AB  - Kin and multilevel selection theories predict that genetic structure is required
      for the evolution of cooperation. However, local competition among relatives can
      limit cooperative benefits, antagonizing the evolution of cooperation. We show
      that several ecological factors determine the extent to which kin competition
      constrains cooperative benefits. In addition, we argue that cooperative acts that
      expand local carrying capacity are less constrained by kin competition than other
      cooperative traits, and are therefore more likely to evolve. These arguments are
      particularly relevant to microbial cooperation, which often involves the
      production of public goods that promote population expansion. The challenge now
      is to understand how an organism's ecology influences how much cooperative groups
      contribute to future generations and thereby the evolution of cooperation.

PMID- 19409653
TI  - Systematic long-term observations of the global carbon cycle.
AB  - Imagine a meeting convened to avert a global financial crisis where none of the
      finance ministers had access to reliable information on changes in the stock
      market, national gross domestic product or international trade flows. It is
      hardly conceivable. Yet the infinitely more existence-threatening planetary
      social and ecological crisis we refer to as 'global change' (comprising the
      linked issues of biogeochemical, climate, biotic and human system change) is in
      an analogous situation. Our information on the profound and accelerating changes
      currently depends to an unacceptable degree on serendipity, individual passion,
      redirected funding and the largely uncoordinated efforts of a few nations. The
      thesis of this paper is that navigation of the very narrow 'safe passages' that
      lie ahead requires a comprehensive and systematic approach to Earth observations,
      supported by a globally coordinated long-term funding mechanism. We developed the
      argument based on observations of the carbon cycle, because the issues there are
      compelling and easily demonstrated, but we believe the conclusions also to be
      true for many other types of observations relating to the state and management of
      the biosphere.

PMID- 19409654
TI  - Benzaldehyde dehydrogenase from chitosan-treated Sorbus aucuparia cell cultures.
AB  - Cell cultures of Sorbus aucuparia respond to the addition of chitosan with the
      accumulation of the biphenyl phytoalexin aucuparin. The carbon skeleton of this
      inducible defense compound is formed by biphenyl synthase (BIS) from benzoyl-CoA
      and three molecules of malonyl-CoA. The formation of benzoyl-CoA proceeds via
      benzaldehyde as an intermediate. Benzaldehyde dehydrogenase (BD), which converts
      benzaldehyde into benzoic acid, was detected in cell-free extracts from S.
      aucuparia cell cultures. BD and BIS were induced by chitosan treatment. The
      preferred substrate for BD was benzaldehyde (K(m)=49 microM). Cinnamaldehyde and
      various hydroxybenzaldehydes were relatively poor substrates. BD activity was
      strictly dependent on the presence of NAD(+) as a cofactor (K(m)=67 microM).

PMID- 19409655
TI  - Growth and functional responses of different cultivars of Lotus corniculatus to
      aluminum and low pH stress.
AB  - Aluminum toxicity is an important stress factor in acid soils. Growth,
      respiration and permeability properties of root cells were studied in five
      cultivars of Lotus corniculatus subjected to aluminum (Al) or low pH stress. The
      cultivars showed significant differences in root elongation under stress
      conditions, which correlated with changes in membrane potential (E(M)) of root
      cortical cells. A pH drop from 5.5 to 4.0 resulted in significant membrane
      depolarization and root growth inhibition. The strongest inhibition was observed
      in cv. Sao Gabriel (33.6%) and least in cv. UFRGS (25.8%). Application of an
      extremely high Al concentration (2mM) stopped the root growth in cv. INIA Draco,
      while inhibition in cv. UFRGS reached only 75%. The E(M) values of cortical cells
      of Lotus roots varied between -115 and -144mV. Treatment with 250microM of
      AlCl(3) (pH 4) resulted in rapid membrane depolarization. The extent of the
      membrane depolarization ranged between 51mV (cv. UFGRS) and 16mV (cv. INIA
      Draco). The membrane depolarization was followed by a loss of K(+) from Al
      treated roots (2mM Al) and resulted in a decrease of the diffusion potential
      (E(D)). The total amount of K(+) in Al-treated roots dropped from 31.4 to
      16.8micromolg(-1) FW in sensitive cv. INIA Draco, or from 26.1 to 22.7micromolg(
      1) FW in tolerant cv. UFGRS. The rate of root respiration under control
      conditions as well as under Al treatment was higher in cv. INIA Draco than in cv.
      UFRGS. Al-induced inhibition of root respiration was 21-34% of the control.

PMID- 19409656
TI  - Medical school dermatology curriculum: are we adequately preparing primary care
      physicians?
AB  - BACKGROUND: There is a lack of information regarding the dermatology learning
      needs of primary care physicians and residents. OBJECTIVE: To determine
      dermatologic topics that primary care physicians consider important and to
      determine primary care residents' ratings of the teaching adequacy of these
      topics in the undergraduate medical curriculum. METHODS: Primary care physicians
      and residents were surveyed regarding the importance and teaching adequacy of 17
      dermatologic content areas. RESULTS: Ninety-two primary care physicians
      identified 13 dermatologic content areas important for their practices. Two
      hundred fifty-two primary care residents identified 8 adequately taught topics
      and 9 inadequately taught topics. LIMITATIONS: Internal medicine and family
      medicine physicians and residents from only 10 regions were surveyed. CONCLUSION:
      Seventeen content areas can be divided into 3 categories: dermatologic topics
      that are important and adequately taught, topics that are unimportant, and a
      group of important, yet inadequately taught content areas. This latter group
      should be further integrated into dermatology curricula at U.S. medical schools.

PMID- 19409657
TI  - Randomized, controlled trial of antibiotics in the management of community
      acquired skin abscesses in the pediatric patient.
AB  - STUDY OBJECTIVE: Emergency department visits for skin and soft tissue infections
      are increasing with the discovery of community-acquired methicillin-resistant
      Staphylococcus aureus. Whether abscesses treated surgically also require
      antibiotics is controversial. There are no published pediatric randomized
      controlled trials evaluating the need for antibiotics in skin abscess management.
      We determine the benefits of antibiotics in surgically managed pediatric skin
      abscesses. METHODS: This was a double-blind, randomized, controlled trial.
      Pediatric patients were randomized to receive 10 days of placebo or trimethoprim
      sulfamethoxazole after incision and draining. Follow-up consisted of a visit/call
      at 10 to 14 days and a call at 90 days. Primary outcome was treatment failure at
      the 10-day follow-up. Secondary outcome was new lesion development at the 10- and
      90-day follow-ups. Noninferiority of placebo relative to trimethoprim
      sulfamethoxazole for primary and secondary outcomes was assessed. RESULTS: One
      hundred sixty-one patients were enrolled, with 12 lost to follow-up. The failure
      rates were 5.3% (n=4/76) and 4.1% (n=3/73) in the placebo and antibiotic groups,
      respectively, yielding a difference of 1.2%, with a 1-sided 95% confidence
      interval (CI) (-infinity to 6.8%). Noninferiority was established with an
      equivalence threshold of 7%. New lesions occurred at the 10-day follow-up: 19 on
      placebo (26.4%) and 9 on antibiotics (12.9%), yielding a difference of 13.5%,
      with 95% 1-sided CI (-infinity to 24.3%). At the 3-month follow-up, 15 of 52
      (28.8%) in the placebo group and 13 of 46 (28.3%) in the antibiotic group
      developed new lesions. The difference was 0.5%, with 95% 1-sided CI (-infinity to
      15.6%). CONCLUSION: Antibiotics are not required for pediatric skin abscess
      resolution. Antibiotics may help prevent new lesions in the short term, but
      further studies are required.

PMID- 19409658
TI  - Irukandji syndrome case series from Australia's Tropical Northern Territory.
AB  - STUDY OBJECTIVE: We describe Irukandji syndrome (a painful hypercatecholaminergic
      condition caused by jellyfish envenoming) in Australia's Northern Territory.
      METHODS: We collected prospectively a standardized data set on patients
      presenting to health facilities in the Northern Territory. Additional cases were
      identified retrospectively. Data collected included demographic, geographic,
      seasonal, and environmental features, as well as sting details, clinical
      manifestations, investigations, management, and outcomes. RESULTS: From 1990 to
      2007, Irukandji syndrome affected 87 people. Age ranged from 1 to 51 years (64%
      male victims; 41% children [63% indigenous]). Activities associated with stings
      included snorkeling or scuba diving (35%) and swimming (29%). Stings commonly
      occurred in water greater than 2 m deep (63%), with fine weather (73%) and still
      or light breeze (70%). Seasonal variation was bimodal; peaks in May and October
      corresponded to prevailing offshore winds in the Darwin and Gove areas,
      respectively. Pain was severe (65%), with rapid onset (<30 minutes in 79%). Sting
      lesions (visible in 63%) were mild, and nematocysts (detected in 7 cases) had
      variable morphology. Systemic features were common, including hypertension and
      ECG abnormalities. Severe complications included troponin-level increases (2
      cases) and cardiomyopathy with ventricular tachycardia (1 case), but no
      fatalities. Management included vinegar as first aid (66%), parenteral opioids
      (70%) (range 2 to 82.5 mg morphine equivalents in adults), and magnesium sulfate
      (3 cases). Hospital admission (49%) and aeromedical retrieval (16%) were
      commonplace. CONCLUSION: Irukandji syndrome in the Northern Territory was
      clinically consistent with previous studies but had distinct seasonal,
      geographic, and environmental features. Indigenous children in remote coastal
      communities are at risk, and there is room for improvement in prevention and
      management.

PMID- 19409660
TI  - [Role of the HIV-1 gp120 V1/V2 domains in the induction of neutralizing
      antibodies].
AB  - The development of a preventive vaccine against human immunodeficiency virus type
      1 (HIV-1) provides hope for control of the pandemic over the coming years.
      Nevertheless, it is clear that one of the greatest difficulties in achieving this
      vaccine is the high mutation rate of the virus, which enables it to evade the
      host's immune response. The production of neutralizing antibodies (NAb) against
      the HIV-1 envelope proteins is believed to play an important role in controlling
      the infection and in providing effective protection following vaccination.
      Several studies have shown that the V1/V2 domain of the HIV-1 gp120 envelope
      protein is involved in viral tropism during infection, in masking conserved
      neutralizing epitopes, in the conformational changes occurring after coreceptor
      binding, and in NAb induction. Nonetheless, this domain has been poorly
      investigated. However, because the V1/V2 domain is highly glycosylated, numerous
      studies have determined the influence of carbohydrates on NAb production. The
      present review focuses on the importance of NAb directed against epitopes of the
      variable regions, mainly V1/V2, their importance in protecting against HIV-1
      infection, and the role these regions play in evading the immune response.
      Lastly, we will discuss the importance of NAb in the search for an effective
      vaccine against HIV-1.

PMID- 19409661
TI  - Severe enterovirus disease in febrile neonates.
AB  - INTRODUCTION: Fever in newborn infants may be due to an invasive infection with
      potential morbidity and mortality. Our aim was to describe the characteristics
      and outcome of group of febrile neonates with severe enterovirus infection
      compared to a group of neonates with severe bacterial infection. PATIENTS AND
      METHODS: Prospective study including all neonates (<29 days old) admitted to a
      teaching hospital for fever (>38 degrees C), with positive bacterial cultures or
      enterovirus detection in sterile samples, from September 2003 to December 2004.
      Clinical information, analytical data at admission (complete leukocyte count and
      C-reactive protein concentrations), blood, urine, and cerebrospinal fluid culture
      results, molecular detection of enterovirus by polymerase chain reaction (PCR),
      and outcome were recorded. RESULTS: Invasive bacterial infections were observed
      in 62 patients: urinary tract infection (n=57, including 8 cases of bacteremia),
      sepsis (n=3), and meningitis (n=2). Molecular tests for enterovirus were positive
      in 10 patients. C-reactive protein values were significantly higher in neonates
      with bacterial infection than in those with enterovirus infection (62,3 versus
      9mg/L, P=0,008). Two patients with Streptococcus agalactiae meningitis, 1 with
      Staphylococcus aureus sepsis and 3 with enterovirus infection (manifested as
      myocarditis, hepatitis, and meningoencephalitis) required admission to the
      pediatric intensive care unit. Among these, 1 newborn with S. agalactiae and 2 of
      the 3 with enterovirus infection died. CONCLUSIONS: In our series, enterovirus
      infection was an important cause of severe invasive disease. Specific viral
      diagnosis can contribute to the management of febrile neonates.

PMID- 19409662
TI  - [Renal tuberculosis and human immunodeficiency virus infection].

PMID- 19409663
TI  - [Congenital cytomegalovirus infection: is serological screening during pregnancy
      necessary?].
AB  - Primary cytomegalovirus (CMV) infection occurs during pregnancy in 1% to 4% of
      seronegative women and may be transmitted to the fetus in up to 40% of cases. Up
      to 10% of intrauterine CMV infections result in symptomatic congenital disease at
      birth. Half of these children and 13% of those born with asymptomatic infection
      will develop significant clinical sequelae in infancy, especially sensorineural
      hearing loss. Routine CMV screening during pregnancy is not recommended in Spain
      owing to the absence of an effective CMV vaccine, the lack of preventive measures
      or therapy during pregnancy, the difficulty in diagnosing a reactivated
      infection, and the possibility of symptomatic congenital infections in children
      of immune women. However, sensitive and specific methods to diagnose primary
      maternal and fetal infection now exist, and new preventive and therapeutic
      measures have been developed. Currently, these procedures are not universally
      available and need to be tested in larger trials. Furthermore, the prevalence of
      seropositive status in pregnant women, the frequency of congenital infection, and
      the percentage of infants born with hearing impairment and mental retardation in
      our country are not known. Therefore, it would not be appropriate to introduce
      routine screening for CMV in pregnancy at the present time. However, increased
      efforts should be made to inform women about congenital CMV disease, to develop
      the diagnosis of fetal infection and methods to determine the extent of
      involvement in the case of suggestive ultrasound findings, and to treat
      symptomatic infected newborns with antivirals to reduce hearing impairment.

PMID- 19409664
TI  - [Genotyping of Chlamydia trachomatis in an area of northern Spain].
AB  - INTRODUCTION: Circulating Chlamydia trachomatis genotypes that cause infection in
      our geographic area were studied with the aim of detecting possible
      epidemiological peculiarities. METHODS: A total of 177 strains obtained between
      2006 and 2008 were genotyped using a PCR with primers targeting the ompA gene,
      and later sequenced. RESULTS: The most frequent genotypes were: E (45.3%), D
      (15.3%), G (10.2%) and F (9.6%). Other genotypes found were: B, H, I, J, K and
      LGV II. CONCLUSION: The molecular assay used had a high yield (89%).

PMID- 19409665
TI  - Determination of the invasive capacity of nonpigmented rapidly growing
      mycobacteria by two different in vitro assays.

PMID- 19409667
TI  - [Usefulness of synovial fluid inoculation in blood culture bottles for diagnosing
      Kingella kingae septic arthritis: state of the question].

PMID- 19409666
TI  - [Impact of initial cytomegalovirus viral load on efficacy of preemptive therapy
      with ganciclovir in allogeneic stem cell transplant recipients].
AB  - OBJECTIVE: To study the impact of initial cytomegalovirus (CMV) viral load on
      virological response to ganciclovir preemptive therapy in allogeneic stem cell
      transplant (SCT) recipients after 4 weeks of treatment. METHODS: Eighty-one
      consecutive allogeneic SCT recipients were included. Preemptive therapy was
      initiated when CMV load was positive for 2 consecutive weeks or when a viral load
      >5000copies/mL was detected in 1 sample. If viral load was >400copies/mL after 2
      weeks of treatment, maintenance treatment with ganciclovir was continued for 2
      additional weeks. Virological failure was defined as a CMV load >400copies/mL
      after 4 weeks of treatment. RESULTS: Ganciclovir preemptive therapy was initiated
      in 32 patients (39.5%) who had 39 episodes of CMV replication. Virological
      failure occurred in 16 patients (50%) after 18 episodes of replication (46%).
      Clinical failure additionally occurred in 2 episodes (5%). The only risk factor
      for virological failure was a peak viral load >20,000copies/mL at the beginning
      of treatment (OR 5.88; 95% CI: 1.49-25, P=.03). The main risk factor for CMV
      replication >20,000copies/mL at the start of treatment was the presence of grade
      II-IV acute graft-versus-host-disease (OR 16; 95% CI: 8.5-45). CONCLUSION: CMV
      viral load >20,000copies/mL is the main risk factor for virological failure after
      4 weeks of ganciclovir preemptive therapy following SCT.

PMID- 19409668
TI  - [Evaluation of the status of patients with severe infection, criteria for
      intensive care unit admittance. Spanish Society for Infectious Diseases and
      Clinical Microbiology. Spanish Society of Intensive and Critical Medicine and
      Coronary Units].
AB  - Recent studies have shown that early attention in patients with serious
      infections is associated with a better outcome. Assistance in intensive care
      units (ICU) can effectively provide this attention; hence patients should be
      admitted to the ICU as soon as possible, before clinical deterioration becomes
      irreversible. The objective of this article is to compile the recommendations for
      evaluating disease severity in patients with infections and describe the criteria
      for ICU admission, updating the criteria published 10 years ago. A literature
      review was carried out, compiling the opinions of experts from the Sociedad
      Espanola de Enfermedades Infecciosas y Microbiologia Clinica (SEIMC, Spanish
      Society for Infectious Diseases and Clinical Microbiology) and the Sociedad
      Espanola de Medicina Intensiva, Critica y Unidades Coronarias (SEMICYUC, Spanish
      Society for Intensive Medicine, Critical Care and Coronary Units) as well as the
      working groups for infections in critically ill patients (GEIPC-SEIMC and GTEI
      SEMICYUC). We describe the specific recommendations for ICU admission related to
      the most common infections affecting patients, who will potentially benefit from
      critical care. Assessment of the severity of the patient's condition to enable
      early intensive care is stressed.

PMID- 19409669
TI  - [Hypertension, HIV infection, and highly active antiretroviral therapy].
AB  - The decline in mortality resulting from the use of highly active antiretroviral
      therapy (HAART) has been accompanied by an increase in metabolic complications
      that produce accelerated atherosclerosis. Hypertension is one of the most
      important cardiovascular risk factors. Little is known about the impact of HAART
      on blood pressure, and it is uncertain whether chronic HIV infection or HAART
      have a role in the development of hypertension. In this study, the research on
      the relationships between hypertension and HIV infection published to date is
      reviewed. Antiretroviral therapy appears to have a modest impact on blood
      pressure and to be partially mediated by the metabolic changes occurring with
      this treatment.

PMID- 19409670
TI  - [Microbiological diagnosis of ocular infections].
AB  - The recent increase in the practice of ocular surgery and widespread use of
      contact lenses have led to an increase in the incidence of severe ocular
      infections. Inadequate management of these infections can result in irreversible
      loss of vision. Microbiological diagnosis is essential when the lesions are non
      specific, recurrent, or unresponsive to antibiotic therapy, but is hampered by
      the difficulty of analyzing limited sample volumes containing small inocula. This
      document presents a review of the most important ocular infections according to
      the structure affected, and describes the most common causes of these infections
      and the situations in which a microbiological diagnosis is recommended.
      Information is included on the sample type and sampling methods, sample transport
      to the laboratory, and laboratory management and processing techniques, with
      special attention to liquid culture media. The yield of smear examination and
      culture of each type of ocular specimen is specified. Lastly, the molecular
      methods recently developed for the diagnosis of ocular fungal infections and
      Acanthamoeba infections are described.

PMID- 19409671
TI  - [Stability: a factor to consider in antibiotic-lock solutions].
AB  - Antibiotic-lock therapy (ALT) has been related to a reduction in the need for
      catheter withdrawal in patients with catheter-related infection. The stability of
      the antimicrobial solutions used in ALT has not been sufficiently investigated. A
      systematic literature review was performed to identify articles including studies
      on the stability of ALT solutions. Nine studies fulfilled the inclusion criteria
      requiring specific drug determination techniques, and no apparent drug
      alterations were observed. The main microorganisms studied were Staphylococcus
      spp., Pseudomonas aeruginosa, and Klebsiella pneumoniae. The antibiotics included
      cefazolin, ceftazidime, ciprofloxacin, colistin, gentamicin,
      ticarcillin/clavulanate, and vancomycin in solution, administered alone or in
      combinations, with or without heparin. All solutions were fairly stable except
      for ciprofloxacin at a concentration of 10mg/mL. Few studies applied strict
      criteria to assess the stability of antibiotic solutions used in ALT; hence, the
      currently available data are limited. Therefore, it seems advisable to include
      appropriate stability studies in further research on the use of ALT.

PMID- 19409672
TI  - [Molecular characterization of Pseudomonas aeruginosa isolates in Cantabria,
      Spain, producing VIM-2 metallo-beta-lactamase].
AB  - INTRODUCTION: Pseudomonas aeruginosa strains producing metallo-beta-lactamases
      (MbetaL) are uncommon in Spain. This study describes the characterization of 9
      new clonally related multiresistant P. aeruginosa isolates possessing the bla(VIM
      2) gene in Cantabria (Northern Spain). METHODS: P. aeruginosa clinical strains (1
      per patient) were isolated in the Microbiology Service of Marques de Valdecilla
      University Hospital between January 2004 and December 2006. Identification and
      preliminary susceptibility studies were performed with the MicroScan WalkAway
      system (Dade Behring, Sacramento, CA) and results were verified by a
      microdilution reference method. RESULTS: MICs of imipenem and meropenem for the 9
      isolates ranged from 32 to 128 and 16 to 64 microg/mL, respectively. Nine
      isolates had a single Rep-PCR pattern and were intermediate or resistant to
      ceftazidime, cefepime, gentamicin, tobramycin, amikacin and ciprofloxacin. Eight
      of the 9 isolates were susceptible to aztreonam. Hydrolysis activity of imipenem
      in MbetaL-positive isolates ranged from 162+/-18 to 235+/-28 pmol/min/microg
      protein and was abolished in the presence of 5 mM EDTA. All isolates possessed an
      integron with genes aac(6')32, bla(VIM-2) and a putative transposase-encoding
      gene, flanked by the conserved 5'CS and 3'CS regions. CONCLUSION: In the clinical
      isolates studied, the presence of MbetaL VIM-2 sufficed to explain their
      resistance to carbapenems.

PMID- 19409673
TI  - [Differentiation of species within the Mycobacterium tuberculosis complex by
      molecular techniques].
AB  - INTRODUCTION: The Mycobacterium tuberculosis complex includes the following
      species: Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium
      bovis, Mycobacterium bovis-BCG, Mycobacterium microti, Mycobacterium caprae,
      Mycobacterium pinnipedii, and Mycobacterium canettii. These species cause
      tuberculosis in humans and animals. Identification of mycobacterial strains has
      classically been performed by phenotype study. Over the last years, laboratories
      have developed several molecular techniques to differentiate between these
      species. The aim of this study is to evaluate these methods and develop a simple,
      fast, identification scheme. MATERIAL AND METHODS: We analyzed 251 strains
      randomly obtained from the strains studied in 2004, and 797 strains received by
      the Reference Laboratory between 2005 and 2007. Phenotype characterization of
      4183 strains isolated during that period was done by studying the colony
      morphology, characteristics in culture, nitrate reduction, niacin accumulation,
      and growth in the presence of thiophen-2-carboxylic acid hydrazide 10 microg/mL
      and pyrazinamide 50 microg/mL. The molecular identification scheme designed was
      as follows: 1) gyrB PCR-RFLP with RsaI, TaqI or SacII and hsp65 RFLP/PCR with
      HhaI., and 2) multiplex-PCR to determine the presence/absence of the RD9 and RD1
      regions. RESULTS: The results showed 100% agreement between phenotype study and
      the molecular scheme. DISCUSSION: This molecular identification scheme is a
      simple and fast method, with 100% sensitivity and specificity, that can be
      implemented in most clinical laboratories at a low cost.

PMID- 19409674
TI  - [Nocardia brasiliensis cellulitis in an injection drug user].

PMID- 19409675
TI  - [First case of community-acquired Panton-Valentine leukocidin-positive (ST88)
      methicillin-resistant Staphylococcus aureus bacteriemia in Spain in a patient
      with meningitis].

PMID- 19409676
TI  - [Embolic stroke as the first manifestation of Bartonella henselae endocarditis in
      an immunocompetent patient].

PMID- 19409677
TI  - Synthesis and antiprotozoal activities of dicationic bis(phenoxymethyl)benzenes,
      bis(phenoxymethyl)naphthalenes, and bis(benzyloxy)naphthalenes.
AB  - A series of 37 dicationically substituted bis(phenoxymethyl)benzene
      bis(phenoxymethyl)naphthalene, and bis(benzyloxy)naphthalene analogues of
      pentamidine was prepared and evaluated for antiprotozoal activities and
      cytotoxicity in in vitro. 1,3-Bis(4-amidinophenoxymethyl)benzene (1) was the most
      active against Trypanosoma brucei rhodesiense (IC(50)=2.1 nM). 1,3-Bis[4-(N
      isopropylamidino)phenoxymethyl]benzene (2) was most active against Plasmodium
      falciparum (IC(50)=3.6 nM) and displayed a selectivity index more than 50 times
      greater than that of pentamidine. Several other compounds displayed lower
      antiplasmodial IC(50) values and higher selectivity indices relative to
      pentamidine. 1,4-Bis(4-amidinophenoxymethyl)benzene (14) was the most active
      against Leishmania donovani (IC(50)=1.3 microM). Compound 2 displayed the
      greatest activity against T. b. rhodesiense in vivo, curing three of four
      infected mice dosed intraperitoneally at 5 mg/kg x 4 days.

PMID- 19409678
TI  - [A new medical concept: the metallic profile].
AB  - Over the past decade great progress has been made in metals and metalloids
      analysis. This analysis is a basic stage in toxicity assessment and is
      indispensable in achieving a realistic evaluation of substance toxicity. A
      recently introduced technique, inductively coupled plasma mass spectrometry (ICP
      MS) is progressively replacing atomic absorption. This analysis permits multi
      elementary determinations, approximately 30 elements, with an optimal gain in
      sensitivity in many biological matrices: i.e. whole blood, plasma, urine, hair,
      nail, biopsy samples. Moreover, this method allows semiquantitative determination
      with an additional 30 supplementary elements, which enables the toxicologist to
      sufficiently estimate the toxic levels and metal exposure. The authors
      demonstrate that the ICP-MS could be very useful for a wide range of clinical
      applications. Furthermore, this procedure offers new exploration possibilities in
      various fields such as clinical toxicology, forensic toxicology as well as work
      place testing or environmental exposure and permits epidemiologic studies. This
      analytical method in fact also provides a new scientific approach. To our
      knowledge we are the first to propose: the metallic profile.

PMID- 19409679
TI  - Blending of the eyelid-cheek junction and removal of protruding fat: an intraoral
      approach to blepharoplasty of the lower eyelid.
AB  - Blepharoplasty is one of the most common aesthetic procedures done today. The
      protruding fat and lid-cheek junction are the most conspicuous signs of aging
      that need attention. During zygomatic reduction by an intraoral approach we found
      occasionally that the orbital fat can be exposed through the perforated
      periosteum at the inferior obital rim. We therefore developed a new
      blepharoplasty procedure using an oral approach. Seventeen patients aged from 26
      to 38 years, of whom six had had a previous unsuccessful blepharoplasty and one
      had a history of injury to the lower lid, were studied. The operation was done
      under an infraorbital nerve block and local anaesthesia through an intraoral
      incision at the upper vestibular groove. The periosteum was raised on the surface
      of the maxilla to the infraorbital rim, and the infraorbital nerve preserved. The
      periosteum and the orbital septum were incised along the whole length of the
      infraorbital rim. The fat that was exposed through the incision was either
      removed or preserved and fixed to the outer soft tissue with sutures. Cosmetic
      results were good and the oral incision healed without infection. Six patients
      developed numbness in the infraorbital region, five of whom recovered within 3
      months; the other recovered by 6 months postoperatively.

PMID- 19409680
TI  - Re: The danger of publishing "unnamed" in anatomy.

PMID- 19409681
TI  - Prognostic factors in malignant tumours of the salivary glands.
AB  - Salivary gland tumours are a relatively rare group of lesions best managed in
      specialist centres. We review some of the factors that influence their prognosis.
      Clinical stage is the most important, with large malignancies having a poor
      prognosis regardless of histological grade and other features such as perineural
      invasion. Even high grade neoplasms may do well when they are small. A helpful
      guide to the management of salivary cancers is the "4 cm" rule.

PMID- 19409682
TI  - The role of socioeconomic indicators on non-alcohol and alcohol-associated
      suicide mortality among women in Finland. A register-based follow-up study of 12
      million person-years.
AB  - This study was to analyse the effects and interrelationships of three
      socioeconomic indicators--education, occupation-based social class and income--on
      non-alcohol and alcohol-associated suicide mortality among women in Finland. The
      register data used comprised the 1990 census records linked to the death register
      for the years 1991-2001 for women who were 25-64 years old in 1990. Adjusted
      relative mortality rates and the relative index of inequality (RII) were
      estimated using Poisson regression. The study population experienced 1926
      suicides, of which 563 (29%) had alcohol intoxication as a contributory cause.
      The age-adjusted effects of education on non-alcohol associated suicide were
      modest, while social class and income related inversely and strongly. The effect
      of social class was partly mediated by income, and social class explained income
      differences to some extent. The associations between these socioeconomic
      indicators and alcohol-associated suicide were stronger, and following adjustment
      for each other large effects were left for education, social class and income.
      Further adjustment for living arrangements had little effect on socioeconomic
      differences in both types of suicide, but practically all of the effects of
      income and some of education and social class were mediated by employment status.
      In conclusion, current material factors are hardly the main underlying drivers of
      socioeconomic differences in suicide among Finnish women. Low social class proved
      to be an important determinant of suicide risk, but the strong independent effect
      of education on alcohol-associated suicide indicates that the roots of these
      differences are probably established in early adulthood when educational
      qualifications are obtained and health-behavioural patterns set.

PMID- 19409683
TI  - [Benign primary cystic lesions of mediastinum in adult: the clinical spectrum and
      surgical treatment].
AB  - BACKGROUND AND OBJECTIVE: The mediastinal cysts form a group of heterogeneous and
      uncommon benign lesions of neoplastic, congenital, or inflammatory conditions.
      The forgoing controversy is how to manage them; surgical removal or observation.
      We reviewed our experience including some rare conditions, emphasizing the
      clinical spectrum and surgical treatment. PATIENTES AND METHODS: This is a
      retrospective review between 2000 and 2007 included 34 cases of primary
      mediastinal cystic lesions. Clinical features, imaging techniques, surgical
      operation, morbidity, mortality and follow-up were analyzed. RESULTS: There were
      18 females (53%) and 16 males (47%), with a mean age+/-standard deviation of
      45.3+/-14.1 years (range: 22-74). Most of cysts were congenital (94%), except
      patients with hydatid disease (6%). 24% of cysts (n=8) were detected in anterior
      mediastinum. Rest of them (n=26) were located in visceral mediastinum. Patients
      usually were symptomatic (61%). Chest pain and discomfort was most common
      symptom, others were dyspnea, cough and hemoptysis, respectively. Cysts excision
      was performed in all cases with an uneventful recovery and with no recurrence in
      long term follow up. CONCLUSIONS: Asymptomatic mediastinal cysts are not rare.
      Surgery is a reliable method of treatment of mediastinal cysts with acceptable
      mortality and morbidity.

PMID- 19409684
TI  - Effects of specular component on color differences of different filler type resin
      composites after aging.
AB  - OBJECTIVE: This study evaluated the effects of specular component mode of
      specular component excluded (SCE) and specular component included (SCI) on color
      changes of different filler type resin composites after aging of 1 week and 1
      year. METHODS: Resin composites and shades used in this study were submicron
      filled Estelite Sigma (Sigma: Inc, A2, A3, B3, C2, OA2, OA3) and nanofilled
      Filtek Supreme XT (XT: Clear, A2E, A2B, A3B, C2B, A2D, A3D). Resin disks of 2mm
      in thickness and final polish with 2400-grit silicon carbide paper were stored in
      100% relative humidity. One-week and 1-year after curing, the colors of the
      composite disks were measured with a spectrophotometer in SCI and SCE modes.
      RESULTS: For both 1-week and 1-year specimens, the values of L* with SCI were
      significantly higher than SCE for all shades of Sigma and XT; however, a* and b*
      were depended on brands and shades. Comparing 1-week and 1-year values, DeltaE*ab
      ranged 1.5 (A3 and B3)-2.9 (Inc) with SCI and 1.4 (A3)-2.9 (Inc) with SCE for
      Sigma, and 1.1 (A3D)-7.1 (Clear) with SCI and 1.4 (A3D)-7.6 (Clear) with SCE for
      XT. The values of DeltaE*ab with SCE were higher than those of SCI for all shades
      of XT; however, for Sigma, the differences varied with shades. CONCLUSION:
      Specular component mode (SCE vs. SCI) significantly influenced L* values;
      however, the color differences affected by aging were dependent on brands and
      shades of the resin composites tested.

PMID- 19409685
TI  - Differentiating interstitial cystitis from similar conditions commonly seen in
      gynecologic practice.
AB  - Interstitial cystitis is a syndrome characterized by pelvic pain, urinary
      urgency/frequency, nocturia, and dyspareunia, with no other identifiable
      etiology. The clinical presentation of interstitial cystitis is similar to that
      of many other conditions commonly seen in female patients, including recurrent
      urinary tract infections, endometriosis, chronic pelvic pain, vulvodynia, and
      overactive bladder. In addition, interstitial cystitis may exist concurrently
      with these conditions. Correct diagnosis is necessary for appropriate treatment
      and improved outcomes. Tools to assist in the diagnosis of interstitial cystitis,
      as well as effective therapies for this condition, are available. A diagnosis of
      interstitial cystitis should be considered in patients with irritative voiding
      symptoms and/or pelvic pain complaints.

PMID- 19409686
TI  - Conservative management of retained trophoblastic tissue and placental polyp with
      diagnostic ambulatory hysteroscopy.
AB  - OBJECTIVE: To analyse the results of our conservative management of retained
      trophoblastic tissue and placental polyp with diagnostic ambulatory hysteroscopy
      and to describe our experience and guidelines. STUDY DESIGN: Descriptive
      retrospective study. Eighty-four women with suspected retained trophoblastic
      tissue after pregnancy underwent hysteroscopic examination and extraction of all
      residual tissue in the office under direct visualization of the uterine cavity,
      without anaesthesia or cervical dilatation. RESULTS: Hysteroscopic examination
      was tolerated by all but one patient. In 82 cases (97.4%), the diagnosis after
      hysteroscopic examination was placental polyp or retained trophoblastic tissue.
      This diagnosis was histologically confirmed in 79 cases (94.7%). In 43.6% (36) of
      the cases, complete evacuation of the uterine cavity was achieved during a single
      hysteroscopic examination. The only complication after hysteroscopy was one case
      of major vaginal bleeding requiring curettage. CONCLUSIONS: Diagnostic-operative
      ambulatory hysteroscopy is a suitable alternative to blind curettage in the
      management of retained trophoblastic tissue. This technique can be performed in
      the office without anaesthesia and with a low rate of complications.

PMID- 19409687
TI  - Karyotyping in symmetrically growth-restricted fetuses.

PMID- 19409688
TI  - Change in knowledge of women about cervix cancer, human papilloma virus (HPV) and
      HPV vaccination due to introduction of HPV vaccines.
AB  - OBJECTIVES: Test knowledge of HPV, cervix cancer awareness and acceptance of HPV
      vaccination of women now and a year ago. STUDY DESIGN: Questionnaires were filled
      out by 305 women visiting four gynaecologists of the Regional Hospital Heilig
      Hart, Tienen, Belgium during two subsequent weeks. Fisher T or Chi(2) were used
      as statistical methods to compare the data with the survey of 381 women exactly
      one year before. RESULTS: Knowledge about HPV as a cause of cervix cancer and the
      presence of a vaccine rose from roughly 50% in 2007 to over 80% in 2008
      (p<0.0001). Level of education and having daughters, sons or no children no
      longer influenced the level of knowledge or willingness to accept the vaccine.
      Most parents favor the age group 12-16 years as an ideal time for vaccination. In
      contrast with the 2007 survey, women below 26 years had now acquired almost
      equivalent knowledge to older women about the virus, cervix cancer and the
      vaccine, but they were far less likely to accept the vaccine due to its cost,
      unless it would be reimbursed (OR 4.2 (1.6-11) p=0.0055). CONCLUSION: One year
      after introduction of the first two HPV vaccines, over 75% of women attending an
      ambulatory gynaecology clinic know HPV causes cervix cancer and that you can get
      vaccinated against it. Compared with a year earlier, young and lower educated
      women had dramatically improved their knowledge. However, women below 26 years
      are less prepared to pay the cost for vaccination if it is not reimbursed.

PMID- 19409689
TI  - Study on the hydrolysis/precipitation behavior of Keggin Al13 and Al30 polymers
      in polyaluminum solutions.
AB  - The hydrolysis/precipitation behaviors of Al(3+), Al(13) and Al(30) under
      conditions typical for flocculation in water treatment were investigated by
      studying the particulates' size development, charge characteristics, chemical
      species and speciation transformation of coagulant hydrolysis precipitates. The
      optimal pH conditions for hydrolysis precipitates formation for AlCl(3),
      PAC(Al13) and PAC(Al30) were 6.5-7.5, 8.5-9.5, and 7.5-9.5, respectively. The
      precipitates' formation rate increased with the increase in dosage, and the
      relative rates were AlCl(3)>>PAC(Al30)>PAC(Al13). The precipitates' size
      increased when the dosage increased from 50 microM to 200 microM, but it
      decreased when the dosage increased to 800 microM. The Zeta potential of
      coagulant hydrolysis precipitates decreased with the increase in pH for the three
      coagulants. The iso-electric points of the freshly formed precipitates for
      AlCl(3), PAC(Al13) and PAC(Al30) were 7.3, 9.6 and 9.2, respectively. The Zeta
      potentials of AlCl(3) hydrolysis precipitates were lower than those of PAC(Al13)
      and PAC(Al30) when pH>5.0. The Zeta potential of PAC(Al30) hydrolysis
      precipitates was higher than that of PAC(Al13) at the acidic side, but lower at
      the alkaline side. The dosage had no obvious effect on the Zeta potential of
      hydrolysis precipitates under fixed pH conditions. The increase in Zeta potential
      with the increase in dosage under uncontrolled pH conditions was due to the pH
      depression caused by coagulant addition. Al-Ferron research indicated that the
      hydrolysis precipitates of AlCl(3) were composed of amorphous Al(OH)(3)
      precipitates, but those of PAC(Al13) and PAC(Al30) were composed of aggregates of
      Al(13) and Al(30), respectively. Al(3+) was the most un-stable species in
      coagulants, and its hydrolysis was remarkably influenced by solution pH. Al(13)
      and Al(30) species were very stable, and solution pH and aging had little effect
      on the chemical species of their hydrolysis products. The research method
      involving coagulant hydrolysis precipitates based on Al-Ferron reaction kinetics
      was studied in detail. The Al species classification based on complex reaction
      kinetic of hydrolysis precipitates and Ferron reagent was different from that
      measured in a conventional coagulant assay using the Al-Ferron method. The
      chemical composition of Al(a), Al(b) and Al(c) depended on coagulant and solution
      pH. The Al(b) measured in the current case was different from Keggin Al(13), and
      the high Al(b) content in the AlCl(3) hydrolysis precipitates could not used as
      testimony that most of the Al(3+) was converted to highly charged Al(13) species
      during AlCl(3) coagulation.

PMID- 19409690
TI  - ETS gene fusions in prostate cancer: from discovery to daily clinical practice.
AB  - CONTEXT: In 2005, fusions between the androgen-regulated transmembrane protease
      serine 2 gene, TMPRSS2, and E twenty-six (ETS) transcription factors were
      discovered in prostate cancer. OBJECTIVE: To review advances in our understanding
      of ETS gene fusions, focusing on challenges affecting translation to clinical
      application. EVIDENCE ACQUISITION: The PubMed database was searched for reports
      on ETS fusions in prostate cancer. EVIDENCE SYNTHESIS: Since the discovery of ETS
      fusions, novel 5' and 3' fusion partners and multiple splice isoforms have been
      reported. The most common fusion, TMPRSS2:ERG, is present in approximately 50% of
      prostate-specific antigen (PSA)-screened localized prostate cancers and in 15-35%
      of population-based cohorts. ETS fusions can be detected noninvasively in the
      urine of men with prostate cancer, with a specificity rate in PSA-screened
      cohorts of >90%. Reports from untreated population-based cohorts suggest an
      association between ETS fusions and cancer-specific death and metastatic spread.
      In retrospective prostatectomy cohorts, conflicting results have been published
      regarding associations between ETS fusions and cancer aggressiveness. In addition
      to serving as a potential biomarker, tissue and functional studies suggest a
      specific role for ETS fusions in the transition to carcinoma. Finally, recent
      results suggest that the 5' and 3' ends of ETS fusions as well as downstream
      targets may be targeted therapeutically. CONCLUSIONS: Recent studies suggest that
      the first clinical applications of ETS fusions are likely to be in noninvasive
      detection of prostate cancer and in aiding with difficult diagnostic cases.
      Additional studies are needed to clarify the association between gene fusions and
      cancer aggressiveness, particularly those studies that take into account the
      multifocal and heterogeneous nature of localized prostate cancer. Multiple
      promising strategies have been identified to potentially target ETS fusions.
      Together, these results suggest that ETS fusions will affect multiple aspects of
      prostate cancer diagnosis and management.

PMID- 19409691
TI  - Testosterone therapy in castrate-resistant prostate cancer: a possible new
      approach.

PMID- 19409692
TI  - An individual patient data meta-analysis of the long-term outcome of randomised
      studies comparing intravesical mitomycin C versus bacillus Calmette-Guerin for
      non-muscle-invasive bladder cancer.
AB  - BACKGROUND: Patients with non-muscle-invasive bladder cancer with an intermediate
      or high risk need adjuvant intravesical therapy after surgery. Based largely on
      meta-analyses of previously published results, guidelines recommend using either
      bacillus Calmette-Guerin (BCG) or mitomycin C (MMC) in these patients. Individual
      patient data (IPD) meta-analyses, however, are the gold standard. OBJECTIVE: To
      compare the efficacy of BCG and MMC based on an IPD meta-analysis of randomised
      trials. DESIGN, SETTING, AND PARTICIPANTS: Trials were searched through Medline
      and review articles. The relevant trial investigators were contacted to provide
      IPD. MEASUREMENTS: The drugs were compared with respect to time to recurrence,
      progression, and overall and cancer-specific death. RESULTS AND LIMITATIONS: Nine
      trials that included 2820 patients were identified, and IPD were obtained from
      all of them. Patient characteristics were 71% primary, 54% Ta, 43% T1, 25% G1,
      58% G2, and 16% G3, and 7% had prior intravesical chemotherapy. Based on a median
      follow-up of 4.4 yr, 43% recurred. Overall, there was no difference in the time
      to first recurrence (p=0.09) between BCG and MMC. In the trials with BCG
      maintenance, a 32% reduction in risk of recurrence on BCG compared to MMC was
      found (p<0.0001), while there was a 28% risk increase (p=0.006) for BCG in the
      trials without maintenance. BCG with maintenance was more effective than MMC in
      both patients previously treated and those not previously treated with
      chemotherapy. In the subset of 1880 patients for whom data on progression,
      survival, and cause of death were available, 12% progressed and 24% died, and, of
      those, 30% of the deaths were due to bladder cancer. No statistically significant
      differences were found for these long-term end points. CONCLUSIONS: For
      prophylaxis of recurrence, maintenance BCG is required to demonstrate superiority
      to MMC. Prior intravesical chemotherapy was not a confounder. There were no
      statistically significant differences regarding progression, overall survival,
      and cancer-specific survival between the two treatments.

PMID- 19409693
TI  - Effects of once-daily tadalafil on erectile function in men with erectile
      dysfunction and signs and symptoms of benign prostatic hyperplasia.
AB  - BACKGROUND: Lower urinary tract symptoms (LUTS) secondary to benign prostatic
      hyperplasia (BPH; BPH-LUTS) may be associated with erectile dysfunction (ED).
      OBJECTIVE: To evaluate the effects of once-daily tadalafil on erectile function
      in men with ED and BPH-LUTS. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis
      of a phase 2-3, multinational, randomized, double-blind, placebo-controlled,
      parallel-group study of men with ED and moderate-to-severe LUTS secondary to BPH
      who reported being sexually active. In contrast to typical ED trials, no sexual
      activity threshold was required to participate. INTERVENTIONS: Screening and 4-wk
      washout period for patients taking BPH and/or ED treatments; 4-wk placebo run-in
      period; then once-daily placebo or tadalafil 2.5, 5, 10, or 20 mg for 12 wk.
      MEASUREMENTS: International Index of Erectile Function-Erectile Function (IIEF
      EF) domain score, International Prostate Symptom Score (IPSS), peak urinary flow
      rate (Q(max)), and postvoid residual volume (PVR). Analyses were performed in men
      who reported being sexually active with a female partner and who expected to
      remain so throughout the study. IIEF-EF data are presented for the BPH/ED
      population overall and for subgroups stratified by baseline age group, body mass
      index, BPH-LUTS severity, prostate-specific antigen, prior alpha-blocker use, and
      prior ED therapy. RESULTS AND LIMITATIONS: Overall, 581 men were included
      (placebo, n=115; tadalafil 2.5 mg, n=113; tadalafil 5 mg, n=117; tadalafil 10 mg,
      n=120; tadalafil 20 mg, n=116). IIEF-EF domain score improvements from baseline
      to end point with tadalafil were 5.4 (2.5 mg), 6.8 (5 mg), 7.9 (10 mg), and 8.2
      (20 mg) versus 2.0 with placebo (least-squares means; all p values <0.001). IIEF
      EF domain score improvements were observed with tadalafil for all subgroup
      analyses, with no significant differences between subgroup or subgroup-by
      treatment interaction terms. IPSS improvements from baseline to end point were
      significantly greater for all tadalafil doses versus placebo (all p values
      <0.05). Changes in Q(max) and PVR were small and not clinically meaningful.
      CONCLUSIONS: These data support the use of once-daily tadalafil in men with ED
      and BPH-LUTS. TRIAL REGISTRATION: http://www.clinicaltrials.gov: NCT00384930.

PMID- 19409694
TI  - Editorial comment on: Effects of once-daily tadalafil on erectile function in men
      with erectile dysfunction and signs and symptoms of benign prostatic hyperplasia.

PMID- 19409695
TI  - Repeated intake of broccoli does not lead to higher plasma levels of sulforaphane
      in human volunteers.
AB  - The plasma pharmacokinetic characteristics of the chemopreventive isothiocyanate
      sulforaphane were determined in six human volunteers following single and
      repeated intake of raw broccoli. Initially, an analytical method utilising LC
      MS/MS, capable of determining low levels of sulforaphane in human plasma was
      developed and validated. The plasma profile of the isothiocyanate best fitted a
      two-compartment pharmacokinetic model. Sulforaphane was rapidly absorbed with
      peak plasma levels being attained within 1.5h, and was characterised by a long
      terminal elimination phase. Repeated intake of broccoli had no impact on the
      pharmacokinetic behaviour or plasma levels of sulforaphane, and there was no
      evidence of accumulation.

PMID- 19409696
TI  - Effect of pro-inflammatory cytokine stimulation on human breast cancer:
      implications of chemokine receptor expression in cancer metastasis.
AB  - Interactions between tumour cells and microenvironments may affect their growth
      and metastasis formation. In search for a better understanding of the role of
      cellular mediators in the progression of cancer, we investigated the effect of
      pro-inflammatory cytokines IL-1, IL-6, TNF-alpha and IFN-gamma on the regulation
      of expression of chemokine receptors CXCR4, CXCR2, CX3CR1, CCR9, and CCR5 in the
      human breast cancer cell line MCF-7. Our results showed that IL-1 increased CXCR4
      expression whereas TNF-alpha increased CX3CR1, CCR9 and CCR5. Interestingly, this
      regulation was not homogeneous, emphasizing the inherent heterogeneity in cancer
      that may be responsive to specific inflammatory microenvironments.

PMID- 19409697
TI  - Stripping voltammetric behaviour of toxic drug nitrofurantoin.
AB  - A simple, sensitive and reproducible squarewave cathodic adsorptive stripping
      voltammetric method has been developed for the determination of nitrofurantoin in
      solubilized system. The objective of the present paper is to investigate the
      redox behaviour of nitrofurantoin by using different voltammetric techniques and
      to establish the methodology for its determination in the presence of
      surfactants. Voltammograms of the drug with cetrimide in phosphate buffers of pH
      2-11 exhibited a single well-defined reduction peak which may be attributed to
      the reduction of -NO(2) group. The reduction process is irreversible over the
      entire pH range studied. The mechanism of reduction has been postulated on the
      basis of controlled potential electrolysis, coulometry and spectral analysis. The
      proposed SWCAdSV voltammetric method allows the determination of nitrofurantoin
      in linear concentration range 2 x 10(-5) to 1 x 10(-7) mol L(-1). The lower limit
      of detection (LOD) and lower limit of quantification (LOQ) are 0.06 and 0.27
      ng/mL, respectively.

PMID- 19409698
TI  - A study on a combined process for the treatment of phenolic resin plant
      effluents.
AB  - The removal of phenol and formaldehyde from phenolic resin plant effluents has
      been studied by using a combined process. In the first step, phenol was removed
      from effluent by solvent extraction. Special attention was paid to the effluent
      with a low content of phenol, which was treated by non-dispersive solvent
      extraction in hollow fibres. It was found that a single module of Liqui-Cel
      2.5in. x 8in. membrane contactor allowed processing approximately 24 L/h of
      effluent with 0.4-0.7 g/L phenol and attaining values as low as 0.5 mg/L in the
      raffinate. Formaldehyde, which was left in phenolic resin plant effluent after
      the removal of phenol, has been treated with hydrogen peroxide in alkaline medium
      and also in acidic medium (Fenton process). In alkaline medium, formaldehyde was
      oxidized with hydrogen peroxide to formate ion, which was recovered by solvent
      extraction. The oxidation of formaldehyde with Fenton process was also studied
      under several operating conditions. It was found that a large amount of hydrogen
      peroxide (i.e. mole ratio H(2)O(2):HCHO>6) was necessary to mineralize more than
      90% HCHO in 1-2h, at atmospheric pressure and 25 degrees C. The combination of
      pressure and high temperature strongly increased the kinetics of the process and
      allowed achieving a very high overall efficiency of the treatment under moderate
      H(2)O(2) dosage.

PMID- 19409699
TI  - Ozone treatment of PAH contaminated soils: operating variables effect.
AB  - A three-level full factorial design has been conducted to assess the influence of
      gas flow-rate, ozone concentration and reaction time on the remediation of soil
      contaminated with four PAHs (namely acenaphthene, phenanthrene, anthracene and
      fluoranthene). Under the operating conditions investigated, reaction time and
      ozone concentration seem to exert a slight positive effect, whereas gas flow-rate
      does not affect the process efficiency. Average conversions (related to non
      ozonated samples) are in the proximity of 50, 70, 60 and 100% for acenaphthene,
      phenanthrene, anthracene and fluoranthene, respectively. A high conversion
      percentage is obtained in the first minutes of the process. Ozone decomposition
      on soil surface can be modelled by its reactions with easily oxidizable organic
      matter, recalcitrant ozonation intermediates and inorganic active sites.

PMID- 19409700
TI  - Using Large Eddy Simulation for understanding vented gas explosions in the
      presence of obstacles.
AB  - In this work, a validated Large Eddy Simulation model of unsteady premixed flame
      propagation is used to study the phenomenology underlying vented gas explosions
      in the presence of obstacles. Computations are run of deflagrating flames in a
      small-scale combustion chamber closed at the bottom end and open at the opposite
      face. A single obstacle is centred inside the chamber. Methane-air mixtures of
      various compositions (ranging from lean to stoichiometric and rich), and
      obstacles with different area blockage ratios (30, 50 and 70%) and shapes
      (circular, rectangular and square cross-section in the flow direction) are
      investigated. All cases are initialized from stagnation. The competition between
      combustion rate and venting rate allows explaining both number and intensity of
      the overpressure peaks observed.

PMID- 19409701
TI  - Application of response surface methodological approach to optimise Reactive
      Black 5 decolouration by crude laccase from Trametes pubescens.
AB  - Response surface methodology (RSM) was applied to optimise the decolouration of
      the diazo dye Reactive Black 5 (RB5) by crude laccase from the white-rot fungus
      Trametes pubescens. The presence of the redox mediator 1-hydroxybenzotriazole
      (HBT) greatly improved the decolouration levels of RB5 by crude laccase from T.
      pubescens. Central composite design (CCD) using RSM with three variables namely
      redox mediator (HBT), dye (RB5) and enzyme (laccase) concentrations was used in
      this study to optimise significant correlation between the effects of these
      variables on the decolouration of RB5. The optimum concentrations of HBT, RB5 and
      laccase were 1.17 mM, 150 mg/l and 500 U/l, respectively, for a maximum
      decolouration of RB5 (about 60% in 20 min). A quadratic model was obtained for
      dye decolouration through this design. The experimental values were in good
      agreement with the predicted ones and the model was highly significant, the
      correlation coefficient being 0.965. Interaction between HBT and RB5
      concentrations, HBT and laccase concentrations and RB5 and laccase concentrations
      were negligible. In addition, when the kinetic parameters for RB5 decolouration
      were calculated according to Hannes-Wolf plot, the following values were
      obtained: K(M) of 260.11 mg/l and V(max) 37.59 mg/l min.

PMID- 19409702
TI  - Electrodialytic remediation of harbour sediment in suspension--evaluation of
      effects induced by changes in stirring velocity and current density on heavy
      metal removal and pH.
AB  - Electrodialytic remediation was used to remove heavy metals from a suspension of
      dredged harbour sediment. The studied metals Cu, Pb, Zn and Cd are normally
      strongly bound in anoxic sediment. Six electrodialytic laboratory remediation
      experiments were made, lasting 14 days and under oxic conditions. The influence
      on the metal removal was investigated by changing current densities and stirring
      velocity of the sediment suspension. Using a current density of 1.0 mA/cm(2) gave
      the highest metal removal. The sediment suspension was partly oxidised when mixed
      into a suspension for the electrodialytic remediation experiments and was further
      oxidised during the experiments. Even at low stirring velocities, oxic conditions
      were obtained. The metal removal was dependent on the achieved pH in the sediment
      and the highest metal removal and corresponding low pH was obtained by using a
      current density of 1.0 mA/cm(2) and a stirring velocity of the sediment
      suspension of 1000rpm. The highest removal obtained was 98% Cd, 78% Zn, 65% Pb
      and 44% Cu after 14 days of remediation. The metal removal was more dependent on
      the stirring velocity than on the current density. When manually stirring the
      sediment suspension or using a stirring velocity of 60 rpm the sediment
      deposited, which led to a slightly higher pH in the sediment and keeping all the
      sediment in suspension is essential for a successful remediation.

PMID- 19409703
TI  - Preparation of the saving-energy sulphoaluminate cement using MSWI fly ash.
AB  - MSWI fly ash was used as a major cement raw material in sintering sulphoaluminate
      cement clinker successfully in the laboratory. Sintering system, mechanical
      performance, hydration process and microstructure of the clinker was investigated
      by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray
      fluorescence spectrometry (XRF), etc. The result shows that the clinker can be
      sintered properly under the temperature of 1200-1300 degrees C and sintered time
      of 120 min. Cl(-) content in the clinker made with MSWI fly ash is about 1.08%.
      However most Cl(-) cannot leach out in water solution from the hardened cement
      paste during curing age between 1d and 28d because of the Cl(-) being combined in
      clinker minerals and its hydrates. The compressive strength of the
      sulphoaluminate cement was high in early age while that developed smoothly in
      later age.

PMID- 19409704
TI  - Removal of arsenite by Fe(VI), Fe(VI)/Fe(III), and Fe(VI)/Al(III) salts: effect
      of pH and anions.
AB  - The removal of arsenate and arsenite from drinking water poses challenges,
      especially when arsenite is present in a significant amount. The removal of
      arsenite by K(2)FeO(4), K(2)FeO(4)/FeCl(3), and K(2)FeO(4)/AlCl(3) salts was
      studied at pH 6.5 and at an initial As concentration of 500 microg As(III)L(-1).
      The arsenite removal in Fe(VI)/Fe(III) and Fe(VI)/Al(III) systems was also
      examined as a function of pH (6.0-8.0). Arsenite was first oxidized by Fe(VI) to
      arsenate, which was subsequently removed through adsorption by Fe(III) or mixed
      Fe(III)-Al(III) oxy/hydroxide phases. Fe(VI)/Al(III) salts had higher removal
      efficiency of arsenite than Fe(VI) and Fe(VI)/Fe(III) salts. A molar ratio of
      6(3/3):1 for Fe(VI)/Al(III) to As(III) decreased arsenite concentration from 500
      to 1.4 microg L(-1) at pH 6.5. Arsenite removal increased with a decrease in pH
      from 8.0 to 6.0 and exhibited less pH dependence in the Fe(VI)/Al(III) system
      than in the Fe(VI)/Fe(III) system. Aluminum chloride salts performed better than
      FeCl(3) and FeCl(3)/AlCl(3) salts (Fe:Al=1:1) in removing As(V) from water.
      Effect of anions (phosphate, silicate, bicarbonate, nitrate, and sulfate) on the
      arsenite removal by Fe(VI)/Al(III) salts at pH 6.5 was examined. Phosphate,
      silicate, and bicarbonate ions interfered with the removal of arsenite in water.
      Nitrate and sulfate had none to minimal effect on arsenite removal.
      Fe(VI)/Al(III) salts showed a potential for removing arsenite below the current
      drinking water standard (10 microg L(-1)).

PMID- 19409705
TI  - Pain in dementia.

PMID- 19409706
TI  - Microelectrical characterizations of junctions in solar cell devices by scanning
      Kelvin probe force microscopy.
AB  - Scanning Kelvin probe force microscopy was applied to the microelectrical
      characterizations of junctions in solar cell devices. Surface Fermi-level pinning
      effects on the surface potential measurement were avoided by applying a bias
      voltage (V(b)) to the device and taking the V(b)-induced potential and electric
      field changes. Two characterizations are presented: the first is a direct
      measurement of Bi-induced junction shift in GaInNAs(Bi) cells; the second is a
      junction-uniformity measurement in a-Si:H devices. In the first characterization,
      using Bi as a surfactant during the molecular beam epitaxy growth of GaInNAs(Bi)
      makes the epitaxial layer smoother. However, the electrical potential measurement
      exhibits a clear Bi-induced junction shift to the back side of the absorber
      layer, which results in significant device degradation. In the second
      characterization, the potential measurement reveals highly non-uniform electric
      field distributions across the n-i-p junction of a-Si:H devices; the electric
      field concentrates much more at both n/i and i/p interfaces than in the middle of
      the i-layer. This non-uniform electric field is due possibly to high defect
      concentrations at the interfaces. The potential measurements further showed a
      significant improvement in the electric field uniformity by depositing buffer
      layers at the interfaces, and this indeed improved the device performance.

PMID- 19409707
TI  - The use of targeted selective treatments against gastrointestinal nematodes in
      milking sheep and goats in Greece based on parasitological and performance
      criteria.
AB  - This study compared the use of targeted selective treatment (TST) with systematic
      whole-flock treatments in 38 dairy sheep and goat farms in Greece. Criteria for
      individual treatments were either parasitological (nematode faecal egg count) or
      performance-based (body condition score or milk yield). The possible effect of
      treatment on resistance to benzimidazole anthelmintics was assessed using the Egg
      Hatch Test. Mean faecal egg counts decreased during the 12-month experimental
      period in all groups, and were lowest in the TST group treated according to
      faecal egg count (P<0.05). The number of sheep and goats treated by TST was
      reduced compared with systematic treatments. Mean thiabendazole-egg death
      dose(50) (TBZ-ED(50)) values from all groups were similar at the beginning and
      end of the study (P>0.05), but significant variation in TBZ-ED(50) was noted over
      the study period in systematically treated goats (P=0.045). Third stage larvae
      belonging to the genera Teladorsagia, Trichostrongylus and Haemonchus were
      dominant throughout the experimental period in all flocks. It was concluded that
      the use of targeted selective treatment reduced the number of anthelmintic
      treatments to achieve a similar level of parasite control or animal production
      and may offer a viable option to combine animal production with effective
      parasite control in Greece.

PMID- 19409708
TI  - Development and field evaluation of a decision support model for anthelmintic
      treatments as part of a targeted selective treatment (TST) regime in lambs.
AB  - The recent focus of strategies to slow the rate of development of anthelmintic
      resistance in gastro-intestinal parasites has centred on the need to better
      manage the parasite population that is unexposed to the drug, i.e. in refugia.
      One strategy involves the use of targeted selective treatments (TST) where
      anthelmintics are only administered to those individuals that are likely to
      benefit from it, rather than to the whole flock. However, there are few TST
      indicators currently available for farmers in temperate environments. Here we
      describe the development and field evaluation of a performance-based decision
      support model to identify individual animals whose performance is suffering from
      nematodoses, and thus, likely to benefit from an anthelmintic treatment. One
      hundred and ninety two twin-suckled lambs were separated into eight groups and
      each grazed on a one-hectare paddock and exposed to one of four anthelmintic
      treatment regimes. Groups of lambs received either: a whole flock anthelmintic
      treatment either every four weeks (neo-suppressive treatment, NST); when clinical
      signs of disease were evident (metaphylactic/therapeutic treatment, MT); at pre
      determined times throughout the grazing season (strategic treatment, SPT) or
      treatment on an individual animal basis as determined by a performance-based
      decision support model that relied on a calculation of the efficiency of nutrient
      utilization (targeted selective treatment, TST). Animal performance and
      parasitological data were recorded every two weeks. Mean faecal egg counts were
      low throughout the season for the NST group and moderate for the MT, SPT and TST
      groups. During the entire grazing season the NST, MT, SPT and TST animals each
      received on average 5.0, 2.0, 3.0 and 2.6 anthelmintic treatments, respectively.
      Compared to the NST animals, cumulative weight gains were 11% lower at the end of
      the grazing season in MT animals, whereas no reduction was observed in either the
      SPT or TST groups. The proposed decision support system appeared to be successful
      in discriminating between animals which were likely to respond favourably to
      anthelmintic treatment and those that were not and provided a quantitative
      estimate of the likely response. Furthermore, 87% of animals that had a pre
      treatment efficiency of nutrient utilization value lower than the suggested
      threshold of the model responded positively to treatment. The potential benefits
      of using the decision support model as a TST indicator for managing the parasite
      population in refugia in temperate environments are discussed.

PMID- 19409709
TI  - Restoration of the shape, location and skin of the severe burn-damaged breast.
AB  - Thermal injuries to the anterior chest in pre-pubescent girls result in breast
      contracture. During puberty, the breast parenchyma develops and grows underneath
      the scars, resulting in being flattened and disfigured. The breast mound, as well
      as the nipple-areolar complex, is partially or completely levelled out and
      displaced. The contours are unclear and the inframammary fold is effaced. This
      feature of the most severe breast contracture still poses a challenge for most
      surgeons. This type of breast contracture can be successfully eliminated with the
      author-suggested, improved free-skin grafting technique. The scars are excised
      and the shifted area of parenchyma is mobilised symmetrically to the border of
      the undamaged breast. Then, the shape and positioning of the breast as well as
      the nipple-areolar complex are reconstructed with the help of circular suturing
      through the fat layer on two to three breast levels. The suture ends are led
      beyond the wound area and are affixed with certain tension contralateral to the
      breast displacement. The suture ends, being in state of tension, are tied into
      untied knots around bolsters and are retained in place for about 3 months. During
      this time, the form and the positioning of the breast can be corrected using the
      traction of the untied sutures; the skin transplants are stabilised, under which
      the scar tissue is formed. Skin transplant and the scar tissue hold the shape and
      positioning of the breast and the sutures can be removed at this stage. In this
      series, 11 patients were operated upon and 13 breasts were reconstructed. Good
      results were achieved in all cases: the breast's shape and skin was restored and
      the positioning was corrected.

PMID- 19409711
TI  - Combined statin/coenzyme Q10 as adjunctive treatment of chronic heart failure.
AB  - Statins and coenzyme Q10 are both used as adjuncts in the treatment of chronic
      heart failure (CHF) due to their anti-inflammatory and antioxidant effects,
      respectively. And both have been variously shown to improve cardiac function in
      patients with CHF. The two agents interact in two ways; statins inhibit coenzyme
      Q10 synthesis through inhibition of HMG-CoA reductase, the rate limiting step in
      cholesterol synthesis, also shared by coenzyme Q10. Secondly, they both exhibit
      their antioxidant effects through activation of the enzyme superoxide dismutase,
      the rate limiting step in nitric oxide metabolism and main antioxidant mechanism
      of coenzyme Q10. We hypothesize that the interaction between statins and coenzyme
      Q10 is more than just a replacement, but a synergistic interaction on superoxide
      dismutase that could result in better cardiac function, improvement in patient
      symptoms, shortening of duration of hospital stay and improvement in patient
      quality of life.

PMID- 19409712
TI  - Comment on "A novel strategy for prefabrication of large and axially vascularized
      tissue engineered bone by using an arteriovenous loop".

PMID- 19409710
TI  - Patterns of cortisol and craving by menstrual phase in women attempting to quit
      smoking.
AB  - Research indicates stress, craving and menstrual phase may play a role in relapse
      to smoking. It remains unknown how these factors may interact during cessation.
      This study describes the relationship between craving and cortisol concentrations
      by menstrual phase during ad libitum smoking and investigates the impact of this
      relationship on time to relapse. Five assessments of cortisol concentrations and
      craving levels were collected the day before smoking cessation in female smokers
      (n=38) during either the follicular (n=21; F) or luteal (n=17; L) phase. Craving
      at wake-up was significantly greater in the F phase than the L phase (2.5+/-1.9
      vs. 1.1+/-1.4; p=0.018; respectively). Decreased levels of morning cortisol
      concentrations and a greater decline from morning to the nadir levels in cortisol
      were associated with increased craving at bedtime in the L (r=-0.68, p=0.002; r=
      0.67, p=0.003; respectively), but not in the F phase. Craving at wake-up was a
      significant predictor of time to relapse (p=0.008). Our results indicate that
      menstrual phase may play a role in the relationship among craving, cortisol
      concentrations, and risk for relapse.

PMID- 19409713
TI  - Hypothesis proved...citric acid (citrate) does improve cancer: a case of a
      patient suffering from medullary thyroid cancer.

PMID- 19409714
TI  - Cervical spinal cord stimulation may prevent cerebral vasospasm by modulating
      sympathetic activity of the superior cervical ganglion at lower cervical spinal
      level.
AB  - Cervical spinal cord stimulation (SCS) has been for many years hypothesized to be
      of use in treatment of cerebral vasospasm after subarachnoid hemorrhage.
      Experiments in animals and research in humans have demonstrated increase in
      cerebral blood flow (CBF), and different theories have been tried to explain
      these observations. Although there are many claims of circulatory improvements in
      these circumstances, no clinical application has yet been established. A complete
      understanding of physiological and anatomic correlation between CBF modulation
      and SCS remain unclear. We strongly believe that the main objective is not to
      treat vasospasm by increasing blood flow but to prevent vasoconstriction of the
      cerebral arteries by a functional sympathectomy. SCS may, at least theoretically,
      work in different ways at the same time: (1) preventing vasoconstriction of
      cerebral arteries by functional sympathectomy, acting at the lower cervical
      levels; and (2) increasing CBF through central pathways, perhaps involving
      brainstem connections, at the upper cervical levels. One of the practical
      implications of this hypothesis would be differential placement of cervical
      spinal cord stimulation electrodes in patients with subarachnoid hemorrhage
      depending on the timing of electrode insertion and presence or absence of
      vasospasm at the time of initial intervention.

PMID- 19409715
TI  - Performing chemotherapy in proper menstrual stage for maximal efficacy in breast
      cancer.

PMID- 19409716
TI  - High-dose folate and dietary purines promote scavenging of peroxynitrite-derived
      radicals--clinical potential in inflammatory disorders.
AB  - Reduced folates have been shown to reconstitute the proper activity of
      "uncoupled" endothelial nitric oxide synthase in inflamed endothlelium. There is
      recent evidence that this phenomenon may reflect an ability of reduced folates to
      scavenge peroxynitrite - or, more likely, nitrogen dioxide and carbonate radicals
      derived from carbonate-induced decomposition of peroxynitrite. This suggests
      that, at least in those tissues capable of achieving high intracellular levels of
      reduced folates following high-dose folate administration, high-dose folate may
      have important anti-inflammatory potential. It would be of interest to examine
      the impact of high-dose folate in rodent models of disorders in which
      peroxynitrite plays a key pathogenic role - including diabetes, septic or
      hemorrhagic shock, ischemia-reperfusion, congestive heart failure, and
      inflammatory mutagenesis. In particular, this strategy may be useful in many
      pathologies in which oxidant-mediated PARP activation leads to cell death or
      dysfunction. Recent evidence that high-dose folate administration preserves
      myocyte viability following cardiac ischemia-reperfusion likely reflects folate's
      impact on the cytotoxicity of peroxynitrite. For use in medical emergencies,
      parenteral leucovorin (racemic 5-formyltetrahydrofolate) is already clinically
      available. Since uric acid can also function physiologically as a scavenger of
      peroxynitrite-derived radicals, supplemental inosine or dietary nucleic acids -
      which raise tissue levels of urate more effectively than does oral uric acid -
      may usefully complement the protective impact of high-dose folate on
      nitroxidative stress. Epidemiological associations of high urate levels with low
      risk for Parkinson's disease may reflect urate's radical scavenging activity, and
      suggest the possible utility of dietary purines in prevention or treatment of CNS
      inflammatory disorders.

PMID- 19409717
TI  - Nanobacteria's potential involvement in enamel repair in caries.
AB  - Dental caries is the accumulation of numerous episodes of demineralization and
      remineralization, rather than a unidirectional demineralization process.
      Demineralization and remineralization occur constantly either simultaneously or
      alternately and whether a lesion will progress or be repaired depends upon the
      predominant process over periods. Even if fluoride has demonstrated the anti
      caries effect by shifting the demineralization/remineralization balance
      favorably, little is known about non-fluoride action in favor of the balance and
      the effect of fluoride could not fully explain enamel repair in caries. Recently,
      in vitro experiments demonstrated enamel repair by synthetic apatite nanocrystals
      which showed the strong affinity, excellent biocompatibility, mechanical
      improvement, and a higher resistance to acids than apatite from teeth. This
      reminds us of a controversial microorganism called nanobacteria (NB) which form
      nanocrystalline apatite around themselves. Although NB have been detected in some
      pathological calcifications, epidemiologic literature suggests that they are
      widespread present in the healthy people blood. Considering the similarity of
      synthetic nanocrystalline apatite to that of NB and blood circulation
      communicating with saliva, we put forward a hypothesis that NB may act in enamel
      surface just like what the synthetic nanocrystalline apatite does in vitro to
      repair enamel in caries.

PMID- 19409718
TI  - Relationship between perioperative inflammatory response and postoperative
      cognitive dysfunction in the elderly.
AB  - After surgery and anesthesia, many elderly patients show a decline in cognitive
      function. This condition is called postoperative cognitive dysfunction (POCD).
      POCD, a distressing complication after surgery, is independently associated with
      poor short-term and long-term outcomes. Many pathophysiological mechanisms have
      been implicated in development of POCD, but the exact cascade leading to its
      development is unclear. Animal studies show that cytokines from inflammatory
      response are involved in with cognitive dysfunction. Simultaneously, emerging
      evidences indicate that inflammatory response represents a potential pathogenic
      factor in many central cognitive diseases. A similar story may be occurring
      during perioperative process in patients. Surgical trauma, anesthesia, and stress
      response induced perioperative nonspecific inflammatory response. We hypothesize
      that perioperative inflammatory response promotes the development of POCD in
      elderly surgical patients, and some measures against perioperative inflammatory
      response should be considered as a new pathway to prevention of POCD.

PMID- 19409719
TI  - Did natural selection for increased cognitive ability in humans lead to an
      elevated risk of cancer?
AB  - Despite the overall genetic similarity that exists between humans and
      chimpanzees, the species are phenotypically distinct. Among the most notable
      distinctions are differences in brain size and cognitive abilities. Previous
      studies have shown that significant differences in gene expression exist between
      the human and chimpanzee brain. Integration of currently available gene
      expression data with known metabolic and signaling pathways indicates that the
      expression of genes involved in the programmed cell death of brain neurons is
      significantly different between humans and chimpanzees and predictive of a
      reduced level of neuron apoptosis in the human brain. This pattern of expression
      is generally maintained in other human organs suggesting that apoptosis is
      reduced in humans relative to chimpanzees. We propose that a decreased rate of
      programmed neuron death may have been a consequence of selection for increased
      cognitive ability in humans. Since reduced apoptotic function is associated with
      an increased risk of cancer and related diseases, we hypothesize that selection
      for increased cognitive ability in humans coincidently resulted in an increased
      risk of cancer and other diseases associated with reduced apoptotic function.

PMID- 19409720
TI  - Photons and evolution: quantum mechanical processes modulate sexual
      differentiation.
AB  - This paper will show that the fractional difference in the human gender ratio
      (GR) between the GR(at death) for those born in solar cycle peak years (maxima)
      and the GR(at death) in those born in solar cycle non-peak years (minima), e.g.,
      0.023, divided by Pi, yields a reasonable approximation of the quantum mechanical
      constant, alpha, or the fine structure constant (FSC) approximately 0.007297...
      or approximately 1/137. This finding is based on a sample of approximately 50
      million cases using common, readily available demographic data, e.g., state of
      birth, birth date, death date, and gender. Physicists Nair, Geim et al. had found
      precisely the same fractional difference, 0.023, in the absorption of white light
      (sunlight) by a single-atom thick layer of graphene, a carbon skeleton resembling
      chicken wire fencing. This absorption fraction, when divided by Pi, yielded the
      FSC and was the first time this constant could "so directly be assessed
      practically by the naked eye". As the GR is a reflection of sexual
      differentiation, this paper reveals that a quantum mechanical process, as
      manifested by the FSC, is playing a role in the primordial process of
      replication, a necessary requirement of life. Successful replication is the
      primary engine driving evolution, which at a biochemical level, is a quantum
      mechanical process dependent upon photonic energy from the Sun. We propose that a
      quantum-mechanical, photon-driven chemical evolution preceded natural selection
      in biology and the mechanisms of mitosis and meiosis are manifestations of this
      chemical evolution in ancient seas over 3 billion years ago. Evolutionary
      processes became extant first in self-replicating molecules forced to adapt to
      high energy photons, mostly likely in the ultraviolet spectrum. These events led
      to evolution by natural selection as complex mixing of genetic material within
      species creating the variety needed to match changing environments reflecting the
      same process initiated at the dawn of life. Both evolutionary mechanisms coexist
      and are interactive. The periodic energy of solar maxima is likely modulating the
      human genome from maternal integument to an embryo in utero with non-local
      mechanisms intrinsic to quantum mechanics.

PMID- 19409721
TI  - RISUG: a potential candidate for the entry inhibitor group of antiretroviral
      drugs.
AB  - Entry inhibitors are a group of antiretroviral drug which prevents HIV from
      entering human immune cells. They include both fusion and attachment inhibitors.
      A hypothesis is put forward in which a new male contraceptive drug with proven
      antimicrobial property is proposed as a possible candidate for the entry
      inhibitor group of antiretroviral drugs. The proposed mechanism of action
      involves (i) interaction with gp120 and thereby preventing binding to CD4 and
      (ii) competitive binding with the viral glycoprotein and inhibit the glycoprotein
      - cell surface glyocosaminoglycan Heparan Sulfate (HS) interaction. A new drug
      RISUG (Reversible Inhibition of Sperm Under Guidance) presently undergoing Phase
      III clinical trials throughout India for its contraceptive effect in male has
      also antimicrobial actions. RISUG is a chemical complex of styrene maleic
      anhydride (SMA(AN)) and dimethyl sulfoxide. On injection into the vas deferens,
      it reacts with the components of intravas fluid, the spermatic fluid and gets
      converted to styrene maleic acid (SMA(AC)) and breakdown products like mandelic
      acid. An anti HIV activity of RISUG is likely due to its electrical charge and
      mandelic acid generation. For experimental validation HIV in vitro assays can be
      performed which will involve infectivity assays, luciferase assay and soluble
      gp120 assays. A positive result from the studies will validate the hypothesis.

PMID- 19409722
TI  - In vitro effects of coronary angiography: unknown clinical implications.
AB  - In coronary angiography, contrast media (a non-physiologic solution) comes in
      direct contact with coronary arteries endothelium, and a foreign body, the
      polyurethane and polyethylene material of the cardiac catheter, oscillates on
      endothelium. The endothelium differential responses to various mechanical stimuli
      include: intracellular calcium influx, release of endothelin and substance P,
      vascular free radical generation, enhancement of platelet-derived growth factor-A
      (PDGF-A) mRNA, PDGF-A, upregulation of intracellular adhesion molecule-1 mRNA and
      protein, enhanced lymphocyte adhesion, upregulation of endothelin mRNA and
      protein, and stimulation of low density lipoprotein metabolism, increase of
      interleukin 6 and C-reactive protein. Contrast media effects include: change of
      endothelial cell morphology and exposure of extracellular matrix, increase
      adhesiveness to leukocytes, decrease production of nitrous oxide,
      vasoconstriction with some agents, factor XII activation, increase in the release
      of kallikrein, bradykinin, histamine, serotonin, and leukotriene B4, and variable
      effects of platelet activation and aggregation. Passing the cardiac catheters
      through vascular tree was also noticed to be associated with subclinical
      embolization of aortic debris. Some clinical studies showed that coronary
      angiography resulted in elevation of serum inflammatory markers, specifically in
      patients with elevated baseline levels of these markers. Clinical significance of
      pro-inflammatory effects of coronary angiography, and its long term consequences,
      are not studied. Further studies utilizing non-invasive coronary imaging
      techniques is needed to elucidate such effects.

PMID- 19409723
TI  - Perivascular epithelioid cell tumors of the laryngopharynx: three case reports
      and literature review.
AB  - Perivascular epithelioid cell tumor (PEComa) of the laryngopharynx is extremely
      rare, and no such descriptions have been reported in the literature. This study
      describes the clinical, histological, and immunohistochemical features of three
      cases of laryngopharynx PEComa. The patients (two males and one female) were 38,
      42, and 47 years old, respectively. Their tumors were well-demarcated, gray white
      on the cut surface with focal hemorrhage, and ranged from 3.0 to 5.0cm in
      diameter. Microscopically, the tumors were characterized by an epithelioid
      arrangement of tumor cells, which had abundant clear to pale eosinophilic
      granular cytoplasm, vesicular nuclei, and prominent nucleoli. The stroma was rich
      in capillaries, sinusoidal vasculature, and thick-walled blood vessels. Mitotic
      figures were rare. The tumors showed no cellular atypia, with two of them having
      moderate atypical nuclei focally. Immunohistochemically, the tumor cells were
      diffusely or focally positive for vimentin (3/3), HMB-45 (3/3), melan-A(3/3),
      alpha-smooth muscle actin (3/3), and S-100(1/3). They were uniformly negative for
      CK, Syn, CgA, CD34, CD10, and CD117. Two patients are well, with no evidence of
      disease at 13 and 30 months after surgery, one patient had recurrence at 15
      months after operation. Laryngopharynx PEComas should be regarded as tumors with
      a malignant potential.

PMID- 19409724
TI  - Using histopathology breast cancer data to reduce clinical target volume margins
      at radiotherapy.
AB  - PURPOSE: This study aimed to quantify the incidence and extension of microscopic
      disease around primary breast tumors in patients undergoing breast-conserving
      therapy (BCT), focusing on a potential application to reduce radiotherapy boost
      volumes. METHODS AND MATERIALS: An extensive pathology tumor-distribution study
      was performed using 38 wide local excision specimens of BCT patients. Specimen
      orientation was recorded and microscopic findings reconstructed to assess the
      incidence of microscopic disease around the macroscopic tumor. A model of disease
      spread was built, showing probability of disease extension outside a treated
      volume (P(out,vol)). The model was applied in 10 new BCT patients. Taking
      asymmetry of tumor excision into account, new asymmetric margins for the clinical
      target volume of the boost (CTV(boost)) were evaluated that minimize the volume
      without increasing P(out,TTV) (TTV being total treated volume: V(surgery) +
      CTV(boost)). Potential reductions in CTV(boost) and TTV were evaluated. RESULTS:
      Microscopic disease beyond the tumor boundary occurred isotropically at distances
      > 1 cm (intended surgical margin) and > 1.5 cm (intended TTV margin) in 53% and
      36% of the excision specimens, respectively. In the 10 prospective patients, the
      average P(out,TTV) was, however, only 16% due to larger surgical margins than
      intended in some directions. Asymmetric CTV(boost) margins reduced the CTV(boost)
      and TTV by 27% (20 cc) and 12% (21 cc) on average, without compromising tumor
      coverage. CONCLUSIONS: Microscopic disease extension may occur beyond the current
      CTV(boost) in approximately one sixth of patients. An asymmetric CTV(boost) that
      corrects for asymmetry of the surgical excision has the potential to reduce boost
      volumes while maintaining tumor coverage.

PMID- 19409725
TI  - Combined adjuvant radiochemotherapy with IMRT/XELOX improves outcome with low
      renal toxicity in gastric cancer.
AB  - OBJECTIVES: Adjuvant radiochemotherapy improves survival of patients with
      advanced gastric cancer. We assessed in two sequential cohorts whether improved
      radiotherapy technique (IMRT) together with intensified chemotherapy improves
      outcome vs. conventional three-dimensional conformal radiotherapy (3D-CRT) and
      standard chemotherapy in these patients while maintaining or reducing renal
      toxicity. MATERIALS AND METHODS: Sixty consecutive patients treated for gastric
      cancer either with 3D-CRT (n = 27) and IMRT (n = 33) were evaluated. More than
      70% had undergone D2 resection. Although there was a slight imbalance in R0
      status between cohorts, N+ status was balanced. Chemotherapy consisted
      predominantly of 5-fluorouracil/folinic acid (n = 36) in the earlier cohort and
      mostly of oxaliplatin/capecitabine (XELOX, n = 24) in the later cohort. Primary
      end points were overall survival (OS), disease-free survival (DFS), and renal
      toxicity based on creatinine levels. RESULTS: Median follow-up (FU) of all
      patients in the 3D-CRT group was 18 months and in the IMRT group 22 months
      (median FU of surviving patients 67 months in the 3D-CRT group and 25 months in
      the IMRT group). Overall median survival (and DFS) were 18 (13) months in the 3D
      CRT group and both not reached in the IMRT group (p = 0.0492 and 0.0216).
      Actuarial 2-year survival was 37% and 67% in the 3D-CRT and IMRT groups,
      respectively. No late renal toxicity >Grade 2 (LENT-SOMA scale) was observed in
      either cohort. CONCLUSION: When comparing sequentially treated patient cohorts
      with similar characteristics, OS and DFS improved with the use of IMRT and
      intensified chemotherapy without signs of increased renal toxicity.

PMID- 19409726
TI  - Efficacy of salvage radiotherapy plus 2-year androgen suppression for postradical
      prostatectomy patients with PSA relapse.
AB  - PURPOSE: To determine the efficacy of a combined approach of radiotherapy (RT)
      plus 2-year androgen suppression (AS) as salvage treatment for prostate-specific
      antigen (PSA) relapse after radical prostatectomy (RP). METHODS AND MATERIALS:
      Seventy-five patients with PSA relapse after RP were treated with salvage RT plus
      2-year AS, as per a pilot, prospective study. AS started within 1 month after
      completion of salvage RT and consisted of nilutamide for 4 weeks and buserelin
      acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate
      including freedom from PSA relapse was estimated using the Kaplan-Meier method.
      PSA relapse was defined as a PSA rise above 0.2 ng/mL with two consecutive
      increases over a minimum of 3 months. A Cox regression analysis was performed to
      evaluate prognostic factors for relapse. RESULTS: Median age of the cohort was 63
      years at the time of salvage RT. Median follow-up from salvage RT was 6.4 years.
      All achieved initially complete PSA response (< 0.2) with the protocol treatment.
      Relapse-free rate including the freedom from PSA relapse was 91.5% at 5 years and
      78.6% at 7 years. Overall survival rate was 93.2% at both 5 and 7 years. On Cox
      regression analysis, pT3 stage and PSA relapse less than 2 years after RP were
      significant prognostic factors for relapse. CONCLUSION: The combined treatment of
      salvage RT plus 2-year AS yielded an encouraging result for patients with PSA
      relapse after RP and needs a confirmatory study.

PMID- 19409727
TI  - Weekly low-dose docetaxel-based chemoradiotherapy for locally advanced
      oropharyngeal or hypopharyngeal carcinoma: a retrospective, single-institution
      study.
AB  - PURPOSE: To retrospectively assess the efficacy, toxicity, and prognostic factors
      of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV
      oropharyngeal or hypopharyngeal carcinoma. METHODS AND MATERIALS: Between 2001
      and 2005, 72 consecutive patients with locally advanced oropharyngeal or
      hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR;
      radiation at 60 Gy plus weekly docetaxel [10 mg/m(2)]). Thirty of these patients
      also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5
      fluorouracil) before concurrent chemoradiotherapy. Survival was calculated
      according to the Kaplan-Meier method. The prognostic factors were evaluated by
      univariate and multivariate analyses. RESULTS: The median follow-up was 33
      months, with overall survival, disease-free survival, and locoregional control
      rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%)
      experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred
      in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade > or =3 severe
      hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia
      occurred as a late complication in 2 patients (3%). Multivariate analyses
      identified age, T stage, hemoglobin level, and completion of weekly docetaxel,
      but not NAC, as significant factors determining disease-free survival.
      CONCLUSIONS: Docetaxel is an active agent used in both concurrent and sequential
      chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was
      well tolerated in most subjects. Anemia was the most significant prognostic
      factor determining survival. Further studies are warranted to investigate the
      optimal protocol for integrating docetaxel into first-line chemoradiotherapy
      regimens, as well as the potential additive impact of NAC.

PMID- 19409728
TI  - High-dose rate brachytherapy using inverse planning simulated annealing for
      locoregionally advanced cervical cancer: a clinical report with 2-year follow-up.
AB  - PURPOSE: We present clinical outcomes of image-guided brachytherapy using inverse
      planning simulated annealing (IPSA) planned high-dose rate (HDR) brachytherapy
      boost for locoregionally advanced cervical cancer. METHODS AND MATERIALS: From
      February 2004 through December 2006, 51 patients were treated at the University
      of California, San Francisco with HDR brachytherapy boost as part of definitive
      radiation for International Federation of Gynecology and Obstetrics Stage IB1 to
      Stage IVA cervical cancer. Of the patients, 46 received concurrent chemotherapy,
      43 with cisplatin alone and 3 with cisplatin/5-fluorouracil. All patients had
      IPSA-planned HDR brachytherapy boost after whole-pelvis external radiation to a
      total tumor dose of 85 Gy or greater (for alpha/beta = 10). Toxicities are
      reported according to National Cancer Institute CTCAE v3.0 (Common Terminology
      Criteria for Adverse Events version 3.0) guidelines. RESULTS: At a median follow
      up of 24.3 months, there were no toxicities of Grade 4 or greater and the
      frequencies of Grade 3 acute and late toxicities were 4% and 2%, respectively.
      The proportion of patients having Grade 1 or 2 gastrointestinal and genitourinary
      acute toxicities was 48% and 52%, respectively. Low-grade late toxicities
      included Grade 1 or 2 vaginal, gastrointestinal, and hormonal toxicities in 31%,
      18%, and 4% of patients, respectively. During the follow-up period, local
      recurrence developed in 2 patients, regional recurrence developed in 2, and new
      distant metastases developed in 15. The rates of locoregional control of disease
      and overall survival at 24 months were 91% and 86%, respectively. CONCLUSIONS:
      Definitive radiation by use of inverse planned HDR brachytherapy boost for
      locoregionally advanced cervical cancer is well tolerated and achieves excellent
      local control of disease.

PMID- 19409729
TI  - Equivalent biochemical control and improved prostate-specific antigen nadir after
      permanent prostate seed implant brachytherapy versus high-dose three-dimensional
      conformal radiotherapy and high-dose conformal proton beam radiotherapy boost.
AB  - PURPOSE: Permanent prostate implant brachytherapy (PPI), three-dimensional
      conformal radiotherapy (3D-CRT), and conformal proton beam radiotherapy (CPBRT)
      are used in the treatment of localized prostate cancer, although no head-to-head
      trials have compared these modalities. We studied the biochemical control
      (biochemical no evidence of disease [bNED]) and prostate-specific antigen (PSA)
      nadir achieved with contemporary PPI, and evaluated it against 3D-CRT and CPBRT.
      PATIENTS AND METHODS: A total of 249 patients were treated with PPI at the
      University of California, San Francisco, and the outcomes were compared with
      those from a 3D-CRT cohort and the published results of a high-dose CPBRT boost
      (CPBRTB) trial. For each comparison, subsets of the PPI cohort were selected with
      patient and disease criteria similar to those of the reference group. RESULTS:
      With a median follow-up of 5.3 years, the bNED rate at 5 and 7 years achieved
      with PPI was 92% and 86%, respectively, using the American Society for
      Therapeutic Radiology and Oncology (ASTRO) definition, and 93% using the PSA
      nadir plus 2 ng/mL definition. Using the ASTRO definition, a 5-year bNED rate of
      78% was achieved for the 3D-CRT patients compared with 94% for a comparable PPI
      subset and 93% vs. 92%, respectively, using the PSA nadir plus 2 ng/mL
      definition. The median PSA nadir for patients treated with PPI and 3D-CRT was
      0.10 and 0.40 ng/mL, respectively (p < .0001). For the CPBRT comparison, the 5
      year bNED rate after a CPBRTB was 91% using the ASTRO definition vs. 93% for a
      similar group of PPI patients. A greater proportion of PPI patients achieved a
      lower PSA nadir compared with those achieved in the CPBRTB trial (PSA nadir < or
      =0.5 ng/mL, 91% vs. 59%, respectively). CONCLUSION: We have demonstrated
      excellent outcomes in low- to intermediate-risk patients treated with PPI,
      suggesting at least equivalent 5-year bNED rates and a greater proportion of men
      achieving lower PSA nadirs compared with 3D-CRT or CPBRTB.

PMID- 19409731
TI  - Evaluation of safety in a radiation oncology setting using failure mode and
      effects analysis.
AB  - PURPOSE: Failure mode and effects analysis (FMEA) is a widely used tool for
      prospectively evaluating safety and reliability. We report our experiences in
      applying FMEA in the setting of radiation oncology. METHODS AND MATERIALS: We
      performed an FMEA analysis for our external beam radiation therapy service, which
      consisted of the following tasks: (1) create a visual map of the process, (2)
      identify possible failure modes; assign risk probability numbers (RPN) to each
      failure mode based on tabulated scores for the severity, frequency of occurrence,
      and detectability, each on a scale of 1 to 10; and (3) identify improvements that
      are both feasible and effective. The RPN scores can span a range of 1 to 1000,
      with higher scores indicating the relative importance of a given failure mode.
      RESULTS: Our process map consisted of 269 different nodes. We identified 127
      possible failure modes with RPN scores ranging from 2 to 160. Fifteen of the top
      ranked failure modes were considered for process improvements, representing RPN
      scores of 75 and more. These specific improvement suggestions were incorporated
      into our practice with a review and implementation by each department team
      responsible for the process. CONCLUSIONS: The FMEA technique provides a
      systematic method for finding vulnerabilities in a process before they result in
      an error. The FMEA framework can naturally incorporate further quantification and
      monitoring. A general-use system for incident and near miss reporting would be
      useful in this regard.

PMID- 19409730
TI  - Treatment recommendations for locally advanced, non-small-cell lung cancer: the
      influence of physician and patient factors.
AB  - PURPOSE: To determine the impact of patient age, comorbidity, and physician
      factors on treatment recommendations for locally advanced, unresectable non-small
      cell lung cancer (NSCLC). METHODS AND MATERIALS: We surveyed radiation
      oncologists regarding their recommendations for treatment (chemoradiation,
      radiation alone, chemotherapy alone, or no therapy) for hypothetical patients
      with Stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness
      (none, moderate, or severe chronic obstructive pulmonary disease [COPD]).
      Multinomial logistic regression was used to assess the impact of physician and
      practice characteristics on radiation oncologists' treatment recommendations for
      three scenarios with the least agreement. RESULTS: Of 214 radiation oncologists,
      nearly all (99%) recommended chemoradiation for a healthy 55 year old. However,
      there was substantial variability in recommendations for a 55 year old with
      severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe
      COPD. Physicians seeing a lower volume of lung cancer patients were statistically
      less likely to recommend radiotherapy for younger or older patients with severe
      COPD (both p < 0.05), but the impact was modest. CONCLUSIONS: Nearly all
      radiation oncologists report following the evidence-based recommendation of
      chemoradiation for young, otherwise healthy patients with locally advanced,
      unresectable NSCLC, but there is substantial variability in treatment
      recommendations for older or sicker patients, probably related to the lack of
      clinical trial data for such patients. The physician and practice characteristics
      we examined only weakly affected treatment recommendations. Additional clinical
      trial data are necessary to guide recommendations for treatment of elderly
      patients and patients with poor pulmonary function to optimize their management.

PMID- 19409732
TI  - Gemcitabine-based combination chemotherapy followed by radiation with
      capecitabine as adjuvant therapy for resected pancreas cancer.
AB  - PURPOSE: To report outcomes for patients with resected pancreas cancer treated
      with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy
      followed by capecitabine and radiation. PATIENTS AND METHODS: We performed a
      retrospective review of a series of patients treated at a single institution with
      a common postoperative adjuvant program. Between January 2002 and August 2006, 43
      resected pancreas cancer patients were offered treatment consisting of 4, 21-day
      cycles of gemcitabine 1 g/m(2) intravenously over 30 min on Days 1 and 8, with
      either cisplatin 35 mg/m(2) intravenously on Days 1 and 8 or capecitabine 1500
      mg/m(2) orally in divided doses on Days 1-14. After completion of combination
      chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent
      capecitabine (1330 mg/m(2) orally in divided doses) day 1 to treatment
      completion. RESULTS: Forty-one patients were treated. Median progression-free
      survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5
      months), and median overall survival was 45.9 months. In multivariate analysis a
      postoperative CA 19-9 level of >or=180 U/mL predicted relapse and death. Toxicity
      was mild, with only two hospitalizations during adjuvant therapy. CONCLUSIONS: A
      postoperative adjuvant program using combination chemotherapy with gemcitabine
      and either cisplatin or capecitabine followed by radiotherapy with capecitabine
      is tolerable and efficacious and should be considered for Phase III testing in
      this group of patients.

PMID- 19409733
TI  - Unacceptable cosmesis in a protocol investigating intensity-modulated
      radiotherapy with active breathing control for accelerated partial-breast
      irradiation.
AB  - PURPOSE: To report interim cosmetic results and toxicity from a prospective study
      evaluating accelerated partial-breast irradiation (APBI) administered using a
      highly conformal external beam approach. METHODS AND MATERIALS: We enrolled
      breast cancer patients in an institutional review board-approved prospective
      study of APBI using beamlet intensity-modulated radiotherapy (IMRT) at deep
      inspiration breath-hold. Patients received 38.5 Gy in 3.85 Gy fractions twice
      daily. Dosimetric parameters in patients who maintained acceptable cosmesis were
      compared with those in patients developing unacceptable cosmesis in follow-up,
      using t-tests. RESULTS: Thirty-four patients were enrolled; 2 were excluded from
      analysis because of fair baseline cosmesis. With a median follow-up of 2.5 years,
      new unacceptable cosmesis developed in 7 patients, leading to early study
      closure. We compared patients with new unacceptable cosmesis with those with
      consistently acceptable cosmesis. Retrospective analysis demonstrated that all
      but one plan adhered to the dosimetric requirements of the national APBI trial.
      The mean proportion of a whole-breast reference volume receiving 19.25 Gy (V50)
      was lower in patients with acceptable cosmesis than in those with unacceptable
      cosmesis (34.6% vs. 46.1%; p = 0.02). The mean percentage of this reference
      volume receiving 38.5 Gy (V100) was also lower in patients with acceptable
      cosmesis (15.5% vs. 23.0%; p = 0.02). CONCLUSIONS: The hypofractionated schedule
      and parameters commonly used for external beam APBI and prescribed by the ongoing
      national trial may be suboptimal, at least when highly conformal techniques such
      as IMRT with management of breathing motion are used. The V50 and V100 of the
      breast reference volume seem correlated with cosmetic outcome, and stricter
      limits may be appropriate in this setting.

PMID- 19409734
TI  - [Vaginal tridimensionel ultrasound interest for the assessment of correct Essure
      sterilization micro-insert placement].
AB  - OBJECTIVES: To determine the interest and simplicity of 3D ultrasound for the 3
      month check in place of the recommended routine radiologic in a general
      gynecology practice. PATIENTS AND METHOD: Twenty-five patients had routine
      radiologic and transvaginal 3D ultrasound (Voluson 730 Expert) 3 months after
      placement of Essure micro-insert. RESULTS: Twenty-one 3D acquisitions were
      realized. In all cases, the micro-insert are easily visualized. Ideally, the
      echogenic micro-insert appears in the cornuale portion of the fallopian tube. The
      relationship between the micro insert and the uterine cavity is well documented.
      CONCLUSION: Easy-to-use, good reproducibility, absence of radiation, make the 3D
      ultrasound an interesting alternative for the 3-month check. The coronal view
      gives a directly exploitable document for the surgeon.

PMID- 19409736
TI  - Development of a method to estimate skeletal age at death in adults using the
      acetabulum and the auricular surface on a Portuguese population.
AB  - Aging techniques that use the posterior or middle part of the pelvis are of
      interest because this part of the body is very resistant to decay. In a
      preliminary study, acetabular criteria correlated with age were isolated. In a
      second study, three acetabular criteria and four auricular surface criteria were
      described and it was demonstrated that it is of interest to associate these
      criteria. The goal of the present study was to test these criteria in a larger
      sample and to elaborate a standardized procedure for the use of these criteria.
      The study concerned 462 os coxae (hip bones) of known age and sex. All of the
      criteria are correlated with age. Establishing a score allows a better
      correlation with age with lower intra-/inter-observer variability. Seven
      categories of overall score corresponding to eight age groups were defined and
      the probabilities of belonging to an age group depending on the overall score
      were calculated. The first main advantage of this procedure is that it is still
      applicable when only some parts of the body remain. The other benefit is its
      ability to discriminate older people.

PMID- 19409737
TI  - Nondestructive imaging of hidden figures on license plates by X-ray radiograph.
AB  - In this case, we investigated the modified license plates. The evidences had new
      embossing pressed serial numbers after erasing the original numbers on the
      license plates by hammering. The X-ray radiograph could visualize the hidden
      figures; those were virtually unseen by naked eyes or undetectable by ordinary
      photography. To reveal the erased figures, we performed image processing with
      computer software after X-ray radiographs. It proved to be an efficient
      nondestructive way to visualize the hidden original figures on metals.

PMID- 19409735
TI  - Women who abuse prescription opioids: findings from the Addiction Severity Index
      Multimedia Version Connect prescription opioid database.
AB  - BACKGROUND: Evidence suggests gender differences in abuse of prescription
      opioids. This study aimed to describe characteristics of women who abuse
      prescription opioids in a treatment-seeking sample and to contrast gender
      differences among prescription opioid abusers. METHODS: Data collected November
      2005 to April 2008 derived from the Addiction Severity Index Multimedia Version
      Connect (ASI-MV Connect) database. Bivariate and multivariable logistic
      regression examined correlates of prescription opioid abuse stratified by gender.
      RESULTS: 29,906 assessments from 220 treatment centers were included, of which
      12.8% (N=3821) reported past month prescription opioid abuse. Women were more
      likely than men to report use of any prescription opioid (29.8% females vs. 21.1%
      males, p<0.001) and abuse of any prescription opioid (15.4% females vs. 11.1%
      males, p<0.001) in the past month. Route of administration and source of
      prescription opioids displayed gender-specific tendencies. Women-specific
      correlates of recent prescription opioid abuse were problem drinking, age <54,
      inhalant use, residence outside of West US Census region, and history of drug
      overdose. Men-specific correlates were age <34, currently living with their
      children, residence in the South and Midwest, hallucinogen use, and recent
      depression. Women prescription opioid abusers were less likely to report a pain
      problem although they were more likely to report medical problems than women who
      abused other drugs. CONCLUSIONS: Gender-specific factors should be taken into
      account in efforts to screen and identify those at highest risk of prescription
      opioid abuse. Prevention and intervention efforts with a gender-specific approach
      are warranted.

PMID- 19409738
TI  - Extramedullary hematopoiesis: a rare occurrence in the sinonasal tract.
AB  - Extramedullary hematopoiesis (EMH) is a systemic reaction to inadequate
      hematopoiesis. We report two exceedingly rare cases of EMH involving the
      paranasal sinuses. The first patient, a 30-year-old man, presented with a
      maxillary sinus mass. The lesion was excised by endoscopic surgery: definitive
      histology identified foci of EMH within an inflammatory fibromyxoid pseudotumor.
      The second case occurred in a 29-year-old man affected by intermediate beta
      thalassemia. He was hospitalized with a diagnosis of sphenoid sinus mucocele
      secondary to an ethmoid lesion. The patient underwent endoscopic excision of the
      mass and drainage of the sphenoid mucocele. At definitive histology, a diagnosis
      of EMH was established. Herein, the presenting modalities, imaging profile, and
      treatment options of this rare EMH localization are reviewed.

PMID- 19409739
TI  - Chiari Malformation in otology practice.
AB  - The purpose of the study was to evaluate prevalence, characteristic symptoms, and
      management of Chiari Malformation 1 (CM1). A retrospective chat review was made
      in Otology Tertiary Department including 439 otologic patients referred to the
      Helsinki University Hospital Radiology Department for head magnetic resonance
      imaging (MRI) during 2005 and also among 42 patients seen at the Department of
      Neurosurgery in years 2001-2005 with a diagnosis of CM1. We made a structured
      analysis of medical records focusing on patient history, neurologic symptoms, and
      radiologic findings. For surgical patients, information was collected on
      symptoms, treatment, and operative outcome. The prevalence of CM1 in the 439
      otologic patients was 0.9%. Most CM1 patients sent to the Neurosurgery Department
      were operated on. Two months postoperatively, 26 patients (68%) had benefited
      from the surgery, but 12 patients (32%) experienced no change to symptoms. The
      possibility of CM1 should be borne in mind in patients presenting with atypical
      benign positional vertigo or recurrent facial paresis.

PMID- 19409740
TI  - Eye contact and emotional face processing in 6-month-old infants: advanced
      statistical methods applied to event-related potentials.
AB  - Event-related potential (ERP) studies with infants are often limited by a small
      number of measurements. We introduce a weighted general linear mixed model
      analysis with a time-varying covariate, which allows for the efficient analysis
      of all available event-related potential data of infants. This method allows
      controlling the signal to noise ratio effect on averaged ERP estimates due to
      small and varying numbers of trials. The method enables analyzing ERP data sets
      of infants, which would often not be possible otherwise. We illustrate this
      method by analyzing an experimental study and discuss the advantages in
      comparison to currently used methods as well as its potential limitations. In
      this study, 6-month-old infants saw a face showing a neutral or an angry
      expression in combination with direct or averted eye gaze. We examined how the
      infant brain processes facial expressions and whether the direction of eye gaze
      has an influence on it. We focused on the infant Negative Central ERP component
      (Nc). The neutral expression elicited larger amplitude and peaked earlier than
      the angry expression. An interaction between emotion and gaze was found for Nc
      latency, suggesting that emotions are processed in combination with eye gaze in
      infancy.

PMID- 19409742
TI  - [Clinical signs suggestive of bacterial meningitis in infants].
AB  - Bacterial meningitis is a medical emergency requiring prompt recognition and
      evaluation and urgent initiation of appropriate antibacterial therapy. However,
      early recognition of severe bacterial infection including bacterial meningitis is
      a challenge in infants. Two clinical forms are basically observed in infants and
      young children: firstly, clinical meningitis which is characterized by fever,
      usually greater than 39 degrees C, and poorly specific gastrointestinal signs
      such as refusal of feeding and/or vomiting; irritability, abnormal crying,
      bulging fontanel, unusual generalized seizures occurring before six months of age
      and lasting more than 10 min should draw the clinician's attention and lead
      him/her to perform a lumbar puncture and initiate antibiotics; secondly, severe
      sepsis which is characterized by tachycardia, cold and/or mottled limbs and
      sometimes leg pain which should suggest a meningococcal disease; it is quite
      urgent to administer rapid fluid loading and antibiotic treatment while
      postponing lumbar puncture before the septic cascade evolves towards septic
      shock, extensive hemorrhagic rash, and ischemic limbs. Given the relative
      frequency of viral self-limiting diseases and rarity of serious bacterial
      infections, guidelines were published to guide the clinician's decision when
      dealing with a febrile infant. However, an alternative to these guidelines was
      recently suggested with a more clinically oriented decision-making attitude
      appearing as efficient while limiting hospitalizations.

PMID- 19409741
TI  - [Cross-cultural adaptation difficulties in health quality of life scales for
      developing countries: example of St-George respiratory questionnaire validation
      in Morocco].
AB  - BACKGROUND: In developing countries, quality of life (QoL) is becoming an
      increasingly relevant question. The use, in these countries, of the validated
      English scales could resolve an important problem of a lack of QoL tools noted in
      southern countries. However, this approach raises methodological problems of
      cross-cultural adaptation. This paper underlines the principal difficulties
      related to cross-cultural adaptation of QoL measurement scales based on the
      example of St-George Respiratory Questionnaire (SGRQ) translation from English to
      the Moroccan Arabic language. METHODS: The SGRQ, initially designed in English,
      was translated into dialectical Arabic by four translators following the
      recommended stages of translation and cultural adaptation: translation with
      conceptual and linguistic evaluation, back translation, comparison of the source
      and target versions and verification of the new instrument. RESULTS: During this
      cross-cultural adaptation process, some items were modified to adapt the original
      questionnaire to the Moroccan culture. Because of the great diversity of the
      Moroccan dialectal language, some words were, sometimes, translated into two or
      more equivalents which were put in the brackets in the final version of the
      SGRQ(m). Some questions were not applicable to all the Moroccan population such
      as a question about sports that did not concern women. On the other hand, some
      questions involving the same items posed differently in different dimensions,
      gave rise to confusion or the impression of repetition in the Moroccan Arabic
      version. CONCLUSION: The cross-cultural adaptation process, even if carried out
      in a rigorous way, does not always lead to the best target version and suggests
      it would be useful to develop new scales specific to each culture and at the same
      time, to think about the Trans cultural adaptation.

PMID- 19409743
TI  - [Emergency antibiotherapy and adjuvant treatments for acute bacterial
      meningitis].
AB  - The management of bacterial meningitis is based on the combination of several
      components. The objective of this review is to give an overview of the literature
      concerning both the arguments for urgent antibiotic treatment associated with a
      particular focus on the place of corticosteroids. Among other treatments,
      glycerol seems the best rated but symptomatic measures, which may not be achieved
      by randomized studies, should not be overlooked. Many animal studies explore
      other treatment options, but none can be translated into clinical practice. The
      neuroimaging has been little evaluated despite recent technological advances but
      remains important in monitoring of patients whose evolution is considered
      unfavorable.

PMID- 19409744
TI  - [First and second line antibiotic therapy for bacterial meningitis in infants and
      children].
AB  - The potential severity of meningitis in infants and children requires an
      optimized initial empirical therapy, mainly based on direct cerebro spinal fluid
      (CSF) examination, and rapid therapeutic adaptation according to bacterial
      identification and susceptibility. Combination treatment including cefotaxim (300
      mg/kg per day) or ceftriaxone (100mg/kg per day) and vancomycine (60 mg/kg per
      day) remains the standard first line if pneumococcal meningitis cannot be ruled
      out. A simple treatment with third generation cephalosporin can be used for
      Neisseria meningitidis or Haemophilus influenzae meningitis, aminoglycosides must
      be added in case of Enterobacteriacae, mainly before 3 months of age. Second line
      antibiotic therapy is adapted according to the clinical and bacteriological
      response on Day 2. When the minimal inhibitory concentration (MIC) of
      pneumococcal strain is less than 0.5mg/L, third generation cephalosporin should
      be continued alone for a total of 10 days. In other cases, a second lumbar
      puncture is necessary and the initial regimen, with or without rifampicin
      combination, should be used for 14 days. Amoxicillin during 3 weeks, associated
      with gentamycin or cotrimoxazole is recommended for listeriosis.

PMID- 19409745
TI  - Portal venous diameter in children: normal limits according to age, weight and
      height.
AB  - PURPOSE: To establish the normal limits of portal vein diameter according to age,
      height and weight. MATERIALS AND METHODS: One hundred and sixty-eight healthy
      children, ages ranging from 1 month to 15 years were examined by ultrasound.
      Portal vein diameters at hepatic port, weight and height were recorded. RESULTS:
      A range of normal limits for portal veneous diameter according to age, weight and
      height are obtained and presented in tables. CONCLUSION: Knowing the normals for
      portal venous diameter in every age group in children is mandatory in
      differentiating disease. The tables according to age, weight and height will
      definitely be helpful in the work-up process.

PMID- 19409746
TI  - Potentiometric determination of ionisation constants for diphacinone and
      chlorophacinone in a dioxane-water cosolvent system.
AB  - The purpose of this study was to determine the ionisation constants of two poorly
      soluble compounds, namely diphacinone and chlorophacinone, potentiometrically in
      1,4-dioxane-water mixtures with ibuprofen used as a standard. In this study,
      Gran's method was employed for the calibration of glass electrode in cosolvent
      systems with pH measurements based on the concentration scale (p(c)H). Aqueous
      pK(a) values for the tested compounds were obtained by extrapolation on a Yasuda
      Shedlovsky plot. It was demonstrated that the pK(a) for ibuprofen determined
      using this method was consistent with those reported in literature. The technique
      was applied successfully to the two indandione derivatives, diphacinone and
      chlorophacinone. The present study demonstrated that the use of an organic
      cosolvent is effective in improving the solubility of compounds allowing
      potentiometric determination of ionisation constants that are otherwise difficult
      in aqueous solutions.

PMID- 19409747
TI  - Simultaneous determination of magnolin and epimagnolin A in rat plasma by liquid
      chromatography with tandem mass spectrometry: Application to pharmacokinetic
      study of a purified extract of the dried flower buds of Magnolia fargesii, NDC
      052 in rats.
AB  - A purified extract isolated from the dried flower buds of Magnolia fargesii (NDC
      052) is currently being evaluated for phase III clinical trials as a new anti
      asthma drug. A rapid, sensitive and selective liquid chromatography-tandem mass
      spectrometric (LC/MS/MS) method for the simultaneous determination of magnolin
      and epimagnolin A, the major bioactive components of NDC-052, in rat plasma was
      developed. After liquid-liquid extraction with tolterodine as an internal
      standard, magnolin and epimagnolin A were separated on a Luna phenyl-hexyl column
      with the mobile phase of 70% methanol in 10mM ammonium formate. The analytes were
      detected by an electrospray ionization tandem mass spectrometry in the multiple
      reaction-monitoring mode. The standard curves were linear over the concentration
      range of 50-2500ng/mL for magnolin and epimagnolin A in rat plasma. The intra-
      and inter-day coefficients of variation and relative errors for magnolin and
      epimagnolin A at four QC concentrations were 1.5-11.4% and 5.9-12.5%,
      respectively. The lower limits of quantification for magnolin and epimagnolin A
      were 50.0ng/mL using 50microL of plasma. This method was successfully applied to
      the pharmacokinetic study of magnolin and epimagnolin A after an oral
      administration of NDC-052 in male Sprague-Dawley rats.

PMID- 19409748
TI  - Information about prenatal screening for Down syndrome: ethnic differences in
      knowledge.
AB  - OBJECTIVE: To evaluate the provision of information about prenatal screening for
      Down syndrome to women of Dutch, Turkish and Surinamese origins, and to examine
      the effects of this provision on ethnic differences in knowledge about Down
      syndrome and prenatal screening. METHODS: The study population consisted of 105
      Dutch, 100 Turkish and 65 Surinamese pregnant women attending midwifery or
      obstetrical practices in The Netherlands. Each woman was personally interviewed
      for 3 weeks (mean) after booking for prenatal care. RESULTS: Most women reported
      to have received oral and/or written information about prenatal screening by
      their midwife or obstetrician at booking for prenatal care. Turkish and
      Surinamese women less often read the information than Dutch women, more often
      reported difficulties in understanding the information, and had less knowledge
      about Down syndrome, prenatal screening and amniocentesis. Language skills and
      educational level contributed most to the explanation of these ethnic variations.
      CONCLUSION: Although most Dutch, Turkish and Surinamese women reported to have
      received information from their midwife or obstetrician, ethnic differences in
      knowledge about Down syndrome and prenatal screening are substantial. PRACTICE
      IMPLICATIONS: Interventions to improve the provision of information to women from
      ethnic minority groups should especially be aimed at overcoming language
      barriers, and targeting information to the women's abilities to comprehend the
      information about prenatal screening for Down syndrome.

PMID- 19409749
TI  - Testing the effects of educational strategies on comprehension of a genomic
      concept using virtual reality technology.
AB  - OBJECTIVE: Applying genetic susceptibility information to improve health will
      likely require educating patients about abstract concepts, for which there is
      little existing research. This experimental study examined the effect of learning
      mode on comprehension of a genomic concept. METHODS: 156 individuals aged 18-40
      without specialized knowledge were randomly assigned to either a virtual reality
      active learning or didactic learning condition. The outcome was comprehension
      (recall, transfer, mental models). RESULTS: Change in recall was greater for
      didactic learning than for active learning (p<0.001). Mean transfer and change in
      mental models were also higher for didactic learning (p<0.0001 and p<0.05,
      respectively). Believability was higher for didactic learning (p<0.05), while
      ratings for motivation (p<0.05), interest (p<0.0001), and enjoyment (p<0.0001)
      were higher for active learning, but these variables did not mediate the
      association between learning mode and comprehension. CONCLUSION: These results
      show that learning mode affects comprehension, but additional research is needed
      regarding how and in what contexts different approaches are best for educating
      patients about abstract concepts. PRACTICE IMPLICATIONS: Didactic, interpersonal
      health education approaches may be more effective than interactive games in
      educating patients about abstract, unfamiliar concepts. These findings indicate
      the importance of traditional health education approaches in emerging areas like
      genomics.

PMID- 19409752
TI  - A new movement detector to enable people with multiple disabilities to control
      environmental stimulation with hand swing through a commercial mouse.
AB  - This study assessed whether two persons with profound multiple disabilities would
      be able to control environmental stimulation using hand swing and a standard
      mouse with a newly developed mouse driver (i.e. a new mouse driver replaces
      standard mouse driver, and turns a mouse into a precise two-dimensional motion
      detector). The study was performed according to an ABAB design and included a 2
      month post-intervention check. Data showed that both participants significantly
      increased their target response (hand swing) to activate the control system to
      produce environmental stimulation during the B (intervention) phases. This
      performance was maintained at the post-intervention check. Practical and
      developmental implications of the findings were discussed.

PMID- 19409751
TI  - Biceps tendinitis as a cause of acute painful knee after total knee arthroplasty.
AB  - The case report highlights an unusual case of posterolateral knee pain after
      total knee arthroplasty. Tendinitis of the patellar tendon or pes anserinus is a
      common complication after total knee arthroplasty; however, there is no report in
      the literature regarding the biceps femoris tendinitis causing acute pain in the
      early postoperative period. In this case, the biceps tendinitis was diagnosed and
      treated by ultrasound-guided injection into the tendon sheath.

PMID- 19409750
TI  - Focus groups inform a web-based program to increase fruit and vegetable intake.
AB  - OBJECTIVE: To use focus groups to inform a web-based educational intervention for
      increased fruit and vegetable (FV) consumption. METHODS: Twelve groups
      (participants=137, aged 21-65) were recruited from four geographically diverse
      health systems. Four groups were stratified by gender and eight by race (white
      and African American) and gender. Questions included perceptions of healthy
      eating, factors that encourage or serve as barriers to FV consumption and
      features preferred for a web-based educational intervention. RESULTS: Though
      knowledgeable about healthy eating, participants did not know how to achieve or
      always care about healthy nutritional choices. Motivators for FV consumption
      included being role models and health concerns. Barriers included: lack of time,
      expense and FV availability. Website preferences included: visuals, links,
      tailored materials, menu suggestions, goal setting assistance, printable
      summaries and built in motivation. The developers incorporated nearly all
      suggestions. CONCLUSION: Focus groups provided needs-based tactical strategies
      for an online, education intervention targeting factors to improve FV
      consumption. PRACTICE IMPLICATIONS: Focus groups can provide valuable input to
      inform interventions. Further, web-based programs' abilities to offer information
      without time or geographic constraints, with capacity for tailoring and tracking
      progress makes them a valuable addition in the arsenal of efforts to promote
      healthy behaviors.

PMID- 19409753
TI  - Computer-aided diagnosis of peripheral soft tissue masses based on ultrasound
      imaging.
AB  - Medical ultrasound (US) has been widely used for distinguishing benign from
      malignant peripheral soft tissue tumors. However, diagnosis by US is subjective
      and depends on the experience of the radiologists. The rarity of peripheral soft
      tissue tumors can make them easily neglected and this frequently leads to delayed
      diagnosis, which results in a much higher death rate than with other tumors. In
      this paper, we developed a computer-aided diagnosis (CAD) system to diagnose
      peripheral soft tissue masses on US images. We retrospectively evaluated 49 cases
      of pathologically proven peripheral soft tissue masses (32 benign, 17 malignant).
      The proposed CAD system includes three main procedures: image pre-processing and
      region-of-interest (ROI) segmentation, feature extraction and statistics-based
      discriminant analysis (DA). We developed a depth-normalization factor (DNF) to
      compensate for the influence of the depth setting on the apparent size of the
      ROI. After image pre-processing and normalization, five features, namely area
      (A), boundary transition ratio (T), circularity (C), high intensity spots (H) and
      uniformity (U), were extracted from the US images. A DA function was then
      employed to analyze these features. A CAD algorithm was then devised for
      differentiating benign from malignant masses. The CAD system achieved an accuracy
      of 87.8%, a sensitivity of 88.2%, a specificity of 87.5%, a positive predictive
      value (PPV) 78.9% and a negative predictive value (NPV) 93.3%. These results
      indicate that the CAD system is valuable as a means of providing a second
      diagnostic opinion when radiologists carry out peripheral soft tissue mass
      diagnosis.

PMID- 19409754
TI  - Cardiovascular autonomic functions in well-controlled and intractable partial
      epilepsies.
AB  - BACKGROUND: Epilepsy is associated with imbalance of sympathetic and
      parasympathetic activity which may lead to sudden unexplained death in epilepsy
      (SUDEP). Well-controlled (WcE) and intractable epilepsy (IE) subjects may present
      different autonomic profiles, which can be helpful in explaining the
      predisposition of the latter to SUDEP. PURPOSE: To compare inter-ictal
      cardiovascular autonomic function in subjects with partial WcE and IE. METHODS:
      Thirty WcE and 31 IE subjects underwent a battery of autonomic function tests:
      deep breathing, Valsalva maneuver, isometric exercise, cold pressor and tilt
      table. Autonomic tone was assessed by heart rate variability (HRV). Their
      autonomic severity score and anxiety status was also assessed. RESULTS: IE
      subjects had elevated low frequency component (52.0 vs. 37.6, p=0.047) and
      decremented high frequency component (114 vs. 397, p=0.013) of HRV and higher
      diastolic BP (75.62+/-9.77 vs. 68.64+/-0.43, p=0.036). In deep breathing test,
      they had lesser HR changes (20+/-10.18 vs. 29.68+/-11.23, p=0.007) and lower E:I
      (1.29+/-0.16 vs. 1.43+/-0.21, p=0.008). IE subjects had higher dysautonomia (chi
      square 165.0, p<0.0001). CONCLUSIONS: We observed a higher vasomotor tone, higher
      sympathetic tone, lower parasympathetic tone, lower parasympathetic reactivity
      and more severe dysautonomia in the IE subjects. Refractoriness may lead to an
      alteration in cardiovascular autonomic regulation, which might be a predisposing
      factor for SUDEP.

PMID- 19409755
TI  - Development of spike-wave seizures in C3H/HeJ mice.
AB  - C3H/HeJ mice have been reported to have relatively early onset of spike-wave
      discharges (SWD), and a defective AMPA receptor subunit Gria4 as the genetic
      cause. We investigated the time course of SWD development through serial EEG
      recordings in C3H/HeJ mice to better characterize this model. We found that at
      immature postnatal ages of 5-15 days, rare SWD-like events were observed at an
      average rate of 3 per hour, and with relatively broad spikes, irregular rhythm,
      slow frequency (5-6 Hz), and short duration (mean 1.75 s). This was followed by a
      transitional period of increasing SWD incidence, which then stabilized in mature
      animals at age 26-62 days, with SWD at an average rate of 45 per hour, narrower
      spike morphology, regular rhythm, higher frequency (7-8 Hz), and longer duration
      (mean 3.40s). This sequence of maturational changes in SWD development suggests
      that effects of early intervention could be tested in C3H/HeJ mice over the
      course of a few weeks, rather than a few months as in rats, greatly facilitating
      future research on anti-epileptogenesis.

PMID- 19409756
TI  - Association of adiponectin and metabolic syndrome among patients taking atypical
      antipsychotics for schizophrenia: a cohort study.
AB  - INTRODUCTION: Adiponectin, an adipocyte-derived hormone controlling lipid and
      carbohydrate metabolism, has been suggested to be a biomarker for metabolic
      syndrome in the general population. This study investigated the association
      between adiponectin levels and metabolic syndrome in patients treated with
      atypical antipsychotics. METHODS: Anthropometric and metabolic parameters and
      serum adiponectin levels were assessed in hospitalized patients with
      schizophrenia who had used the same atypical antipsychotic for at least 3 months.
      Retrospective reviews of the patients' medical records were conducted to obtain
      demographic data and pretreatment characteristics. RESULTS: The study included
      567 schizophrenia patients treated with clozapine (n=231), olanzapine (n=94) and
      risperidone (n=242), for an average of 45.8+/-27.8 months. The prevalence of
      metabolic syndrome among all subjects was 23.8%. The clozapine group had a higher
      prevalence of metabolic syndrome (28.7%) than did the olanzapine (24.2%) and
      risperidone groups (19.5%) (P=0.039), and the clozapine group had lower levels of
      adiponectin (8.46+/-6.02 mg/mL) than did the olanzapine (10.26+/-4. 9 mg/mL) and
      risperidone groups (10.69+/-7.43 mg/mL) (P=0.001). Adiponectin level was
      negatively correlated with body mass index (BMI) increase after initiation of
      antipsychotic treatment. Cross-sectional regression analysis showed that age
      (OR,=1.042, P=0.001), BMI (OR=1.404, P<0.0001), and adiponectin level (OR=0.862,
      P<0.0001) were significant factors in the presence of metabolic syndrome.
      Significant predictors of metabolic syndrome were age at initiation of
      antipsychotic treatment (OR=1.04, P=.007), BMI at initiation of antipsychotic
      treatment (OR=1.44, P<0.0001), BMI increase after initiation of antipsychotic
      treatment (OR=1.40, P<0.0001), and adiponectin level (OR=0.86, P<0.0001).
      CONCLUSION: Lower levels of adiponectin and weight gain after taking
      antipsychotics are associated with higher risk of metabolic syndrome in patients
      taking atypical antipsychotics.

PMID- 19409757
TI  - Dream content in chronically-treated persons with schizophrenia.
AB  - Many clinical, laboratory and non-laboratory studies have examined dream content
      reported by patients with schizophrenia but findings have been variable and
      inconsistent. Using both questionnaire-based measures and laboratory REM sleep
      awakenings, we investigated dream content in 14 patients with schizophrenia (mean
      age=25.5+/-3.2 years) under atypical antipsychotic medication and 15 healthy
      controls (mean age=22.3+/-4.2 years). The relationship between eye movement
      density during REM sleep and dream content was also explored. Questionnaire data
      revealed that when compared to controls, patients with schizophrenia report
      experiencing a greater number of nightmares but no significant differences were
      found on other measures including overall dream recall, presence of recurrent
      dreams, and frequency of specific emotions. 39 dream reports were collected from
      each group following awakenings from REM sleep. Laboratory dream narratives from
      the patients were shorter and, after controlling for report length, most
      significant differences in dream content between the two groups disappeared with
      the exception of a greater proportion of unknown characters in the participant
      group. Patients with schizophrenia spontaneously rated their dream reports as
      being less bizarre than did controls, despite a similar density of bizarre
      elements as scored by external judges. Finally, both groups had a comparable
      density of rapid eye movements during REM sleep but a significant positive
      correlation between eye-movement density and dream content variables was only
      found in controls. Taken together, the findings suggest that dream content
      characteristics in schizophrenia may reflect neurocognitive processes, including
      emotional processing, specific to this disorder.

PMID- 19409758
TI  - Inhibition of protein kinase CK2 induces E2F1 nuclear export, formation of
      p21/E2F1 complexes and suppression of DNA synthesis in normal human epidermal
      keratinocytes.

PMID- 19409759
TI  - Consensus statement on the management of invasive candidiasis in Intensive Care
      Units in the Asia-Pacific Region.
AB  - Invasive candidiasis has emerged as an important nosocomial infection, especially
      in critically ill patients. The incidence of candidaemia in Intensive Care Units
      (ICUs) is 5- to 10-fold higher than in the entire hospital and the crude
      mortality rate of patients with candidaemia is between 35% and 60%. Candida
      albicans remains the predominant cause of invasive candidiasis in ICUs, followed
      by Candida tropicalis, Candida glabrata and Candida parapsilosis. Invasive
      isolates of Candida spp. remain highly susceptible to fluconazole (>90%
      susceptible), although among Asia-Pacific countries the susceptibility rate of C.
      glabrata to fluconazole varies widely from 22% to 72%. Early diagnosis and prompt
      initiation of antifungal therapy are crucial for the effective treatment of
      invasive candidiasis. However, invasive candidiasis is difficult to diagnose
      owing to its non-specific clinical features, and delayed therapy is a major
      contributor to poor outcomes. Combining clinical risk factors with Candida
      colonisation parameters appears promising for guiding early interventions.
      Because of considerable regional variability, local epidemiological knowledge is
      critical in the effective management of invasive candidiasis among ICU patients
      in Asia-Pacific.

PMID- 19409760
TI  - MALDI-TOF-MS for rapid detection of staphylococcal Panton-Valentine leukocidin.
AB  - Toxin-producing gram-positive bacteria are responsible for emerging and life
      threatening infections in humans worldwide. Both rapid toxin detection and
      adapted therapy are essential to limit the morbidity due to such toxins,
      especially staphylococcal Panton-Valentine leukocidin (PVL). Here we describe the
      use of a mass spectrometry profile generated by matrix-assisted laser
      desorption/ionisation time-of-flight (MALDI-TOF) followed by ClinProTools 2.0
      software analysis to find a reproducible model able to identify PVL in
      Staphylococcus aureus strains. Eighty-one S. aureus strains were used and tested
      for the presence of PVL, toxic shock syndrome toxin (TSST-1) and mecA genes. The
      peak at 4448 mass-to-charge ratio (m/z) was the most relevant peak to
      differentiate between PVL-producing and non-PVL-producing S. aureus. A model
      using only this peak had an overall recognition capability of 100% and an overall
      cross-validation of 77.07%. Prospective evaluation of the model allowed two cases
      of PVL-producing strains to be detected within a few minutes during the time of
      care and before polymerase chain reaction (PCR) results. Our study represents a
      proof of concept for the use of such rapid technology as a point-of-care method
      to identify potential lethal toxin quickly. We believe that such a rapid method
      will be timely to help change the therapeutic strategy and could be used in the
      future for other pathogens and infectious diseases.

PMID- 19409761
TI  - Artesunate plus sulfamethoxypyrazine/pyrimethamine for the treatment of cutaneous
      leishmaniasis: a double-blind, placebo-controlled clinical trial.

PMID- 19409762
TI  - Evaluation of the quinupristin/dalfopristin breakpoints for Enterococcus faecium.

PMID- 19409763
TI  - Prevalence of qnr determinants among extended-spectrum beta-lactamase-positive
      Enterobacteriaceae clinical isolates in southern Stockholm, Sweden.
AB  - Three hundred and nineteen extended-spectrum beta-lactamase-positive
      Enterobacteriaceae clinical isolates were screened for qnr genes. Twelve isolates
      were positive for qnr, including one qnrA1, two qnrB1, three qnrB2, one qnrB4,
      one qnrB6 and four qnrS1. No qnr-positive strains were identified among the
      isolates recovered before 2006. The first qnr-positive Escherichia coli was
      detected from a patient in 2006. qnr genes remained rare in E. coli (6/288;
      2.1%), but appeared to be more prevalent in Klebsiella pneumoniae (4/25; 16%) and
      Enterobacter cloacae (2/3; 66.7%). All qnr-positive isolates were resistant to
      nalidixic acid while presenting varied susceptibilities to fluoroquinolones.
      Isolates harbouring qnrB4 or qnrB6 were highly resistant to all the
      fluoroquinolones tested. Their high-level resistance is associated with multiple
      chromosomal substitutions in gyrA and parC. Alterations at codons Ser-83 and Asp
      87 in GyrA and at codons Ser-80 and Glu-84 in ParC were observed in these
      isolates.

PMID- 19409764
TI  - Physicochemical and toxicological properties of novel amino acid-based
      amphiphiles and their spontaneously formed catanionic vesicles.
AB  - The design of efficient liposomal systems for drug delivery is of considerable
      biomedical interest. In this context, vesicles prepared from cationic/anionic
      surfactants may offer several advantages, mainly due to their spontaneity in
      formation and long-term stability. There is also an impending need to produce
      less toxic, more biocompatible amphiphiles, while maintaining the desirable
      aggregation properties. In this work, we present data for acute toxicity to
      Daphnia magna (IC(50)), and potential ocular irritation (HC(50)) for some newly
      prepared ionic surfactants with dodecyl chains, derived from the amino acids
      tyrosine (Tyr), serine (Ser), hydroxyproline (Hyp) and lysine (Lys). The
      micellization behavior of the compounds, evaluated from surface tension
      measurements, is presented and compared to more conventional ionic amphiphiles.
      Two types of spontaneouly formed catanionic vesicles, composed either by a
      dodecyltrimethylammonium bromide (DTAB)/Lys-derivative and or Ser-/Lys-derivative
      mixture, have also been tested for their ecotoxicity and hemolytic potential. All
      the micelle-forming surfactants as well as the vesicle-containing mixtures are
      found to have lower ecotoxicity than the reference surfactant DTAB. Moreover, the
      results from hemolysis and hemoglobin denaturation tests show that the Tyr- and
      Lys-derivatives are moderately irritant, whereas the Hyp- and Ser- ones are just
      slightly irritant. Even more significantly, the vesicle-containing mixtures
      exhibit lower hemolytic activity than the neat surfactants, a positive result for
      their potential use in liposomal formulations.

PMID- 19409766
TI  - [Supporting parents and newborns hospitalized in a NICU: interest of group
      setting].
AB  - This article exposes the work realized in a NICU, in a small group of parents and
      their hospitalized premature or ill newborns. The group has a containing
      function, regarding the effects of the traumatism that occurs when such babies
      are born. It allows sharing affects and emotions that are filtered and softened
      through singing. Actually, the parents themselves propose songs or lullabies. The
      group process is described regarding parents and babies: close infant observation
      is an essential part of the process.

PMID- 19409765
TI  - Comparison: adsorption of papain using immobilized dye ligands on affinity
      membranes.
AB  - Novel membranes that involve the immobilization of Reactive Red 120 or Reactive
      Brown 10 as dye ligands were prepared. These were used in the purification of
      papain from papaya powder extracts. Papain adsorption capacities for the Red 120
      and Brown 10 membranes were 143.6 mg/g and 107.3mg/g, respectively. The
      effectiveness of adsorption was demonstrated by Freundlich isotherm proficiency.
      The enzyme was eluted from the respective dye membranes using 1.0M NaCl at pH 6.0
      and yields of over 80% were found for the Red 120-CS (chitosan)-nylon membrane
      whereas only a 50% recovery was possible using the Brown 10-CS-nylon membranes.
      It is concluded that Red 120-CS-nylon membranes could play an active role in the
      separation and purification of papain from crude extracts. This system has the
      potential to be developed for the commercial isolation of the protein.

PMID- 19409767
TI  - [Factor VII deficiency revealed by intracranial hemorrhage].
AB  - Constitutional factor VII deficiency is a hereditary disease with recessive
      autosomic transmission. Its incidence is estimated to be 1/1,000,000 in the
      general population. We report a case of severe factor VII deficiency in infancy
      revealed by an intracranial hemorrhage in a 2-month-old infant. We describe the
      clinical, biological and therapeutic characteristics of this disease.

PMID- 19409768
TI  - Posterior probability profiles for the automated assessment of the recovery of
      patients with stroke from activity of daily living tasks.
AB  - OBJECTIVE: Assessing recovery after stroke has been so far a time consuming
      procedure in which trained clinicians are required. A demand for automated
      assessment techniques arises due to the increasing number of patients with stroke
      and the continuous growth of new treatment options. In this study, we investigate
      the applicability of isometric force and torque measurements in activity of daily
      living tasks to assess the functional recovery after stroke in an automated way.
      METHODS AND MATERIALS: A new hybrid filter-wrapper feature subset technology was
      developed for a new mechatronic platform with the aim to identify the most
      important features and sensors that can distinguish normal controls from patients
      with stroke. We compared 3 different classification algorithms to make the
      distinction: k-nearest neighbors, kernel density estimation and least-squares
      support vector machines. Based on isometric force and torque measurements
      obtained from 16 patients with a first-ever ischemic or haemorrhagic stroke
      within the middle cerebral artery territory, we computed for each subject the
      probability to belong to the class of normal subjects. These probabilities were
      computed during a period of 6 months post-stroke to quantify the level of
      recovery during this period. The posterior probabilities were validated by means
      of a correlation study with the Lindmark modified Fugl-Meyer assessment. RESULTS:
      Patients with stroke and normal controls could be distinguished with an accuracy
      of 98.25% by means of kernel density estimation. The posterior probability
      profiles had a correlation of 76.6% and 80.29% with the global score of the
      Lindmark modified Fugl-Meyer scale and 'part A', the upper extremity subscore,
      respectively. This degree of correlation was as high as obtained with supervised
      scoring techniques such as the Barthel index. CONCLUSION: This study shows that
      the assessment of recovery after stroke can be automated by means of posterior
      probability profiles due to their high correlation with the Fugl-Meyer
      assessment. The posterior probability profiles confirm the importance of a
      recovery within the first weeks after stroke to obtain a higher recovery plateau
      compared to later changes in recovery.

PMID- 19409769
TI  - Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin.
AB  - This experiment pertains to the protective role of naringenin against cadmium
      (Cd)-induced oxidative stress in the liver of rats. Cadmium is a major
      environmental pollutant and is known for its wide toxic manifestations.
      Naringenin is a naturally occurring citrus flavonone which has been reported to
      have a wide range of pharmacological properties. In the present investigation
      cadmium (5mg/kg) was administered orally for 4 weeks to induce hepatotoxicity.
      Liver damage induced by cadmium was clearly shown by the increased activities of
      serum hepatic marker enzymes namely aspartate transaminase (AST), alanine
      transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH),
      gamma glutamyl transferase (GGT) and serum total bilirubin (TB) along with the
      increased level of lipid peroxidation indices (thiobarbituric acid reactive
      substances (TBARS) and lipid hydroperoxides) and protein carbonyl contents in
      liver. The toxic effect of cadmium was also indicated by significantly decreased
      levels of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non
      enzymatic antioxidants (reduced glutathione (GSH), vitamin C and vitamin E).
      Administration of naringenin at a dose of (50mg/kg) significantly reversed the
      activities of serum hepatic marker enzymes to their near-normal levels when
      compared to Cd-treated rats. In addition, naringenin significantly reduced lipid
      peroxidation and restored the levels of antioxidant defense in the liver. The
      histopathological studies in the liver of rats also showed that naringenin
      (50mg/kg) markedly reduced the toxicity of cadmium and preserved the normal
      histological architecture of the tissue. The present study suggested that
      naringenin may be beneficial in ameliorating the cadmium-induced oxidative damage
      in the liver of rats.

PMID- 19409770
TI  - Influence of red clover (Trifolium pratense) isoflavones on gene and protein
      expression profiles in liver of ovariectomized rats.
AB  - Isoflavones such as genistein, biochanin A, formononetin, and glycetin are fairly
      abundant in red clover (Trifolium pratense, Fabaceae) and show estrogenic,
      antioxidant and hypolipidemic activities. To explore these effects mediated by
      red clover extract at the gene and protein levels, female ovariectomized rats
      were treated with an isoflavone rich extract of T. pratense. The experimental
      rats were divided into 2 groups of five animals each: a) control b) experimental
      group (red clover extract treated with 450mg/kg/day for four days). The treatment
      influenced the plasma lipid levels differentially. Plasma LDL concentrations were
      significantly reduced (p<0.05), whereas triglycerides increased (p<0.05). Plasma
      HDL and total cholesterol remained unchanged. The rat livers were examined for
      their differential gene expression by Affymetrix Rae230 DNA microarrays. In
      addition, the total liver proteins were separated by 2D PAGE and proteins, which
      showed differences in their intensities were identified by MALDI-TOF-MS. The
      extract influenced the transcript levels of many novel estrogen and non-estrogen
      responsive genes as well as other regulatory genes. Functional annotations
      indicate that genes involved in metabolic pathways, information processing,
      membrane transport regulation, signal transduction and other cellular processes
      were regulated. Quantitative reverse transcription analysis with real-time PCR
      confirmed that red clover extract regulates genes involved in lipid metabolism
      and antioxidation mechanisms. Proteomic analysis support the potential of red
      clover extract to modulate the lipid metabolism. In summary isoflavone rich red
      clover extract mediates numerous genomic and non-genomic effects, which influence
      besides the lipid metabolism a broad range of cellular functions, including
      metabolic actions, cell cycle regulation and antioxidant activity.

PMID- 19409771
TI  - Instant formation of molecularly imprinted poly(ethylene-co-vinyl
      alcohol)/quantum dot composite nanoparticles and their use in one-pot urinalysis.
AB  - The high stability of quantum dots (QDots) with photoluminescence has led to
      their increased use as imaging approaches in biological systems to replace
      conventional fluorescence labels. The antibodies are generally coated on the
      surface of QDots to the targeting site, and molecular imprinting polymers are
      designed to mimic the antibodies. Hence, quantum dots can be incorporated into
      molecularly imprinted polymers, which provide shape and selectivity, and then
      respond to template rebinding by emitting quenched photoluminescence. In this
      study, poly(ethylene-co-ethylene alcohol) creatinine-, albumin- and lysozyme
      imprinted polymers nanoparticles are synthesized via phase inversion of
      poly(ethylene-co-ethylene alcohol) with various ethylene mole ratios when target
      molecules and hydrophobic quantum dots are mixed within the polymer solution.
      Finally, those particles were prepared for the detection of creatinine, human
      serum albumin and lysozyme in real sample (urine) and compared with commercial
      ARCHITECT ci 8200 system.

PMID- 19409772
TI  - Tumour inflammatory infiltrate predicts survival following curative resection for
      node-negative colorectal cancer.
AB  - BACKGROUND: A pronounced tumour inflammatory infiltrate is known to confer a good
      outcome in colorectal cancer. Klintrup and colleagues reported a structured
      assessment of the inflammatory reaction at the invasive margin scoring low grade
      or high grade. The aim of the present study was to examine the prognostic value
      of tumour inflammatory infiltrate in node-negative colorectal cancer. METHODS:
      Two hundred patients had undergone surgery for node-negative colorectal cancer
      between 1997 and 2004. Specimens were scored with Jass' and Klintrup's criteria
      for peritumoural infiltrate. Pathological data were taken from the reports at
      that time. RESULTS: Low-grade inflammatory infiltrate assessed using Klintrup's
      criteria was an independent prognostic factor in node-negative disease. In
      patients with a low-risk Petersen Index (n=179), low-grade infiltrate carried a
      threefold increased risk of cancer death. Low-grade infiltrate was related to
      increasing T stage and an infiltrating margin. CONCLUSION: Assessment of
      inflammatory infiltrate using Klintrup's criteria provides independent prognostic
      information on node-negative colorectal cancer. A high-grade local inflammatory
      response may represent effective host immune responses impeding tumour growth.

PMID- 19409774
TI  - Synthesis and anaerobic biodegradation of indomethacin-conjugated cellulose
      ethers used for colon-specific drug delivery.
AB  - Water soluble cellulose ethers, including methylcellulose and two
      hydroxyethylcelluloses with different molecular weights, were conjugate with
      indomethacin at room temperature. The chemical structures of the conjugates were
      characterized by FTIR, (1)H NMR and UV-vis spectroscopy. The results confirmed
      that different amounts of IND residues were covalently bonded to cellulose ether
      backbones through ester linkages. Their anaerobic biodegradation in colonic
      fermentation was investigated by gel permeation chromatography, gas
      chromatography and UV-vis spectroscopy. These conjugates were found to have
      different biodegradabilities, depending on the cellulose ether used and the
      amount of conjugated indomethacin residues. In vitro release experiments showed
      that hydroxyethylcellulose-based conjugates with low IND residues content could
      exhibit a sustained drug release behavior in colonic fermentation and were stable
      in the simulated media of the stomach and small intestine. Therefore, they are
      promising candidates for future applications in colon-specific drug delivery.

PMID- 19409773
TI  - Phase I/II study of S-1 plus carboplatin in patients with advanced non-small cell
      lung cancer.
AB  - The objective of this phase I/II study was to determine the recommended dose (RD)
      of S-1 and carboplatin (CBDCA), and to evaluate the efficacy and safety of this
      combination in the treatment of patients with advanced non-small cell lung cancer
      (NSCLC). Chemotherapy-naive patients were treated with S-1 given orally on days 1
      14, and CBDCA infused intravenously on day 1, repeated every 3 weeks. RD was AUC5
      of CBDCA and 80 mg/m(2) of S-1. Nineteen patients were treated at the RD. The
      overall response was 30.8% (95% confidence interval: 17.1-58.3%). The response
      rate in the RD was 36.8% (95% CI: 16.3-61.6%). The median overall survival time
      was 11.1 months (95% CI: 8.1-15.3 months) and the median progression-free
      survival time was 5.0 months (95% CI: 3.6-6.0 months). Major grades 3-4
      toxicities were thrombocytopaenia (47%), anaemia (26%) and infection (16%). This
      is the first report to show promising activity of this combination in phase II,
      including survival data and manageable toxicity, especially in outpatients
      receiving treatment for advanced NSCLC.

PMID- 19409775
TI  - Spent mushroom substrates as component of growing media for germination and
      growth of horticultural plants.
AB  - This research work was conducted in order to investigate the possibility of using
      spent mushroom substrate (SMS) in the production of horticultural seedlings
      replacing part of the peat in the growing media. Three vegetable species with
      different salt sensitivities, the less sensitive being tomato (Lycopersicon
      esculentum var. Muchamiel), the moderately salt-sensitive being courgette
      (Cucurbita pepo L. var. Afrodite F1) and the most salt-sensitive being pepper
      (Capsicum annum L. var. Lamuyo F1) were grown in 12 media containing SMS of two
      types of mushroom (Agaricus bisporus (SMS-AB) and Pleurotus ostreatus (SMS-PO))
      or a mixture of both 50% (v/v) (SMS-50), as well as peat in various ratios. The
      proportions of each residue in the mixtures elaborated with peat were 25%, 50%,
      75% and 100% v/v residue. A substrate of 100% peat was used as control. The
      experiment was arranged in a completely-randomised design with two replicates per
      treatment under greenhouse conditions. Prior to sowing, some physical, physico
      chemical and chemical properties of the growing media were determined and seed
      germination and fresh weight of seedling were also measured. In most of the
      cases, the addition of SMS to the growing media produced an increase in the pH
      values, salt contents, macro and micronutrient concentrations and a decrease in
      the water holding capacity contents in comparison to peat, whereas great
      differences were found in the air capacity values between SMS-based substrates
      and peat. Up to 75% SMS can be used in mixtures with peat for seed germination of
      the plant species studied. Regarding the most suitable SMS-based substrates for
      plant growth, any substrate could be used for tomato seedling production.
      However, all SMS-AB-based substrates and the media containing low dose of SMS-PO
      and SMS-50 were adequate for growth of courgette and pepper.

PMID- 19409776
TI  - Adsorptive features of acid-treated olive stones for drin pesticides:
      equilibrium, kinetic and thermodynamic modeling studies.
AB  - The adsorption behavior of drin pesticides from aqueous solution onto acid
      treated olive stones (ATOS) was investigated using stir bar sorptive extraction
      and gas chromatography coupled with mass spectroscopy. The effects of sorbent
      particle size, adsorbent dose, contact time, concentration of pesticide solution
      and temperature on the adsorption processes were systematically studied in batch
      shaking sorption experiments. Maximum removal efficiency (94.8%) was reached for
      aldrin (0.5 mg L(-1)) using the fraction 63-100 microm of ATOS (solid/liquid
      ratio: 1 g L(-1)). Experimental data were modeled by Langmuir, Freundlich and
      Dubinin-Radushkevich (D-R) isotherms. The Freundlich isotherm model (R(2)=0.98
      0.99) fitted the equilibrium data better than the Langmuir and D-R isotherm
      models, with low sum of error values (SE=1.4-9.2%). The mean adsorption free
      energy derived from the D-R isotherm model (R(2)=0.95-0.99) showed that the
      adsorption of drin pesticides was taken place by weak physical forces, such as
      van der Waals forces and hydrogen bonding. The calculated thermodynamic
      parameters, DeltaH, DeltaS and DeltaG prove that drin pesticides adsorption on
      ATOS was feasible, spontaneous and exothermic under examined conditions. 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.

PMID- 19409777
TI  - Synthesis and therapeutic evaluation of pyridyl based novel mTOR inhibitors.
AB  - A series of novel cyanopyridyl based molecules (1-14) were designed, synthesized
      and probed for inhibition of mammalian target of rapamycin (mTOR) activity.
      Compound 14 was found to be a potent inhibitor of mTOR activity as assessed by
      enzyme-linked immunoassays and Western blot analysis. Most importantly, systemic
      application (intraperitoneal; ip) of compound 14 significantly suppressed
      macroscopic and histological abnormalities associated with chemically-induced
      murine colitis.

PMID- 19409779
TI  - Novel pyridopyrimidine derivatives as inhibitors of stable toxin a (STa) induced
      cGMP synthesis.
AB  - A series of pyridopyrimidine derivatives were synthesized and evaluated for their
      ability to inhibit cyclic nucleotide synthesis in the presence of stable toxin a
      of Escherichia coli. The structure activity relationships around the basic core
      structure were examined and examples with better activity and potentially better
      pharmacological properties are presented.

PMID- 19409778
TI  - Synthesis and biological applications of two novel fluorescent proteins-labeling
      probes.
AB  - Two novel chlorinated fluoresceins 2',4',5',7'-tetrachloro-6-(5-carboxypentyl)
      4,7-dichloro fluorescein succinimidyl ester (1G) and 2',4',5',7'-tetrachloro-6-(3
      carboxypropyl)-4,7-dichlorofluorescein succinimidyl ester (2G) were synthesized
      as fluorescent probes for labeling proteins. Structures of target compounds and
      intermediates were determined via IR, MS, (1)H NMR and element analysis. The
      investigation in immunofluorescence histochemistry showed them had strong
      fluorescence, high photostability and good biocompatibility.

PMID- 19409780
TI  - Discovery of aminoheterocycles as a novel beta-secretase inhibitor class: pH
      dependence on binding activity part 1.
AB  - We have developed a novel series of heteroaromatic BACE-1 inhibitors. These
      inhibitors interact with the enzyme in a unique fashion that allows for potent
      binding in a non-traditional paradigm. In addition to the elucidation of their
      binding profile, we have discovered a pH dependent effect on the binding affinity
      as a result of the intrinsic pK(a) of these inhibitors and the pH of the BACE-1
      enzyme binding assay.

PMID- 19409781
TI  - Synthesis of novel cholesterol-based cationic lipids for gene delivery.
AB  - The new cholesterol-based cationic lipids B, C, and D with an ether linked spacer
      were synthesized by using aminopropyl chain extension with acrylonitrile. The
      cholesterol-based cationic lipid A with carbamoyl linkage were also synthesized
      in order to compare the difference in transfection efficiency of the two linkage
      types. To this end, GFP expression of these cationic lipids was confirmed
      respectively.

PMID- 19409782
TI  - Crown-capped imidacloprid: a novel design and insecticidal activity.
AB  - Imidacloprid (IMI) derivatives conjugated with benzo-15-crown-5 and benzo-18
      crown-6 structures, applied for the first time to explore novel insecticidal
      molecule, elicited strong excitatory toxic signs to the house flies and
      stunningly exhibited three to five times higher insecticidal activity than that
      of the parent IMI, yet the two benzo-crown structures themselves had no effect.

PMID- 19409783
TI  - Binaphthyl scaffolded peptoids via ring-closing metathesis reactions and their
      anti-bacterial activities.
AB  - An efficient synthesis of four new acyclic and four new cyclic binaphthyl-based
      cationic peptoids is described. These compounds had anti-bacterial activities
      with MIC values of 4-62 microg/mL against Staphylococcus aureus.

PMID- 19409784
TI  - Cranial nerves palsy as an initial feature of an early onset distal hereditary
      motor neuropathy--a new distal hereditary motor neuropathy phenotype.
AB  - Distal hereditary motor neuropathy is a heterogeneous group of disorders
      characterised by a pure motor axonal neuropathy. It is occasionally associated
      with additional signs such as facial weakness, vocal cord paralysis, weakness of
      the diaphragm, and pyramidal signs. Although predominantly the inheritance is
      autosomal dominant, all types of inheritance have been described. Here we report
      a Czech family with cranial nerves palsy as an initial feature of a non
      progressive infantile onset dominant distal hereditary motor neuropathy. This
      family may represent a new subtype of distal hereditary motor neuropathy.

PMID- 19409785
TI  - Rapid and cost effective detection of small mutations in the DMD gene by high
      resolution melting curve analysis.
AB  - Duchenne/Becker muscular dystrophy (DMD/BMD) is caused by large deletions or
      duplications in two-thirds of the cases. The remaining one-third DMD patients
      have small mutations in the DMD gene. Screening for such small mutations is a
      daunting and costly task. High resolution melting curve analysis (HR-MCA)
      followed by sequencing for amplicons with altered melting profiles can be used to
      scan DNA for small alterations. We first validated the technique as screening
      procedure for the DMD gene and then screened a group of unrelated 22 DMD/BMD
      patients and 11 females. We managed to identify all previously found mutations by
      means of HR-MCA, which provided its validation. Furthermore, 17 different
      pathogenic mutations were found in the screening group, of which 10 were novel.
      Our results provide validation of HR-MCA as a powerful and inexpensive pre
      sequencing scanning method. This technology is now ready for routine diagnostic
      use on DMD/BMD patients and female carriers.

PMID- 19409786
TI  - Spontaneous motor entrainment to music in multiple vocal mimicking species.
AB  - The human capacity for music consists of certain core phenomena, including the
      tendency to entrain, or align movement, to an external auditory pulse [1-3]. This
      ability, fundamental both for music production and for coordinated dance, has
      been repeatedly highlighted as uniquely human [4-11]. However, it has recently
      been hypothesized that entrainment evolved as a by-product of vocal mimicry,
      generating the strong prediction that only vocal mimicking animals may be able to
      entrain [12, 13]. Here we provide comparative data demonstrating the existence of
      two proficient vocal mimicking nonhuman animals (parrots) that entrain to music,
      spontaneously producing synchronized movements resembling human dance. We also
      provide an extensive comparative data set from a global video database
      systematically analyzed for evidence of entrainment in hundreds of species both
      capable and incapable of vocal mimicry. Despite the higher representation of
      vocal nonmimics in the database and comparable exposure of mimics and nonmimics
      to humans and music, only vocal mimics showed evidence of entrainment. We
      conclude that entrainment is not unique to humans and that the distribution of
      entrainment across species supports the hypothesis that entrainment evolved as a
      by-product of selection for vocal mimicry.

PMID- 19409787
TI  - Maternal effects contribute to the superior performance of extra-pair offspring.
AB  - The explanation for extra-pair mating in female birds remains poorly understood
      and contentious [1-7]. Several leading hypotheses propose that females benefit
      indirectly by enhancing the genetic quality of their offspring, through good
      genes or genetic compatibility effects [1, 8, 9]. Supporting this idea, recent
      studies have identified a range of fitness-related traits for which extra-pair
      offspring (EPO) are superior to their within-pair (WP) half-siblings [10-21].
      However, such performance differences may result from nongenetic maternal effects
      if EPO are positioned earlier in the laying order and benefit from the advantages
      of earlier hatching [22, 23]. Here we show that EPO are larger, heavier, and more
      likely to fledge than their WP half-siblings in a population of blue tits,
      Cyanistes caeruleus. However, extra-pair paternity declined markedly with laying
      order, resulting in EPO generally hatching earlier. After correcting for
      variation in hatch time, none of the observed disparities between EPO and their
      WP half-siblings remained significant. These findings indicate that phenotypic
      comparisons between maternal half-siblings must consider potential hatching-order
      effects and suggest that the evidence for genetic benefits from extra-pair
      copulation may be less compelling than currently accepted. Moreover, the
      overrepresentation of EPO early in the laying order may help explain female extra
      pair mating.

PMID- 19409788
TI  - Bidirectional flower color and shape changes allow a second opportunity for
      pollination.
AB  - Flowers act as "sensory billboards" with multiple signals (color, morphology,
      odor) attracting and manipulating potential pollinators. Many use changing
      signals as indicators that visitation and/or pollination have occurred). Floral
      color change is commonly used to transmit this information (often correlated with
      reduced nectar reward) and can be specifically triggered by pollination or
      visitation. By retaining color-changed flowers, plants benefit from larger floral
      displays but also indicate at close range which flowers are still rewarding (and
      still unpollinated), so that visitors forage more efficiently. However, the
      legume Desmodium setigerum shows a unique ability, if inadequately pollinated, to
      reverse its flowers' color and shape changes. Single visits by bees mechanically
      depress the keel and expose stigma and anthers (termed "tripping"); visits also
      initiate a rapid color change from lilac to white and turquoise and a slower
      morphological change, the upper petal folding downwards over the reproductive
      parts. But flowers receiving insufficient pollen can partially reopen, re
      exposing the stigma, with a further color change to deeper turquoise and/or
      lilac. Thus, most flowers achieve pollination from one bee visit, but those with
      inadequate pollen receipt can reverse their signals, earning a "second chance" by
      eliciting attention from other potential pollinators.

PMID- 19409789
TI  - Chronically CNS-injured adult sensory neurons gain regenerative competence upon a
      lesion of their peripheral axon.
AB  - Several experimental manipulations result in axonal regeneration in the central
      nervous system (CNS) when applied before or at the time of injury but not when
      initiated after a delay, which would be clinically more relevant. As centrally
      injured neurons show signs of atrophy and degeneration, it raises the question
      whether chronically injured neurons are able to regenerate. To address this
      question, we used adult rodent primary sensory neurons that regenerate their
      central axon when their peripheral axon is cut (called conditioning) beforehand
      but not afterwards. We found that primary sensory neurons express regeneration
      associated genes and efficiently regrow their axon in cell culture two months
      after a central lesion upon conditioning. Moreover, conditioning enables central
      axons to regenerate through a fresh lesion independent of a previous central
      lesion. Using in vivo imaging we demonstrated that conditioned neurons rapidly
      regrow their axons through a fresh central lesion. Finally, when single sensory
      axons were cut with a two-photon laser, they robustly regenerate within days
      after attaining growth competence through conditioning. We conclude that sensory
      neurons can acquire the intrinsic potential to regenerate their axons months
      after a CNS lesion, which they implement in the absence of traumatic tissue.

PMID- 19409790
TI  - Experimental evidence for synchronization to a musical beat in a nonhuman animal.
AB  - The tendency to move in rhythmic synchrony with a musical beat (e.g., via head
      bobbing, foot tapping, or dance) is a human universal [1] yet is not commonly
      observed in other species [2]. Does this ability reflect a brain specialization
      for music cognition, or does it build on neural circuitry that ordinarily serves
      other functions? According to the "vocal learning and rhythmic synchronization"
      hypothesis [3], entrainment to a musical beat relies on the neural circuitry for
      complex vocal learning, an ability that requires a tight link between auditory
      and motor circuits in the brain [4, 5]. This hypothesis predicts that only vocal
      learning species (such as humans and some birds, cetaceans, and pinnipeds, but
      not nonhuman primates) are capable of synchronizing movements to a musical beat.
      Here we report experimental evidence for synchronization to a beat in a sulphur
      crested cockatoo (Cacatua galerita eleonora). By manipulating the tempo of a
      musical excerpt across a wide range, we show that the animal spontaneously
      adjusts the tempo of its rhythmic movements to stay synchronized with the beat.
      These findings indicate that synchronization to a musical beat is not uniquely
      human and suggest that animal models can provide insights into the neurobiology
      and evolution of human music [6].

PMID- 19409791
TI  - Endoplasmic and sarcoplasmic reticulum in the heart.
AB  - The concept of the presence of sarcoplasmic reticulum (SR) membrane in the heart
      is widely accepted and has been considered merely to be a different name for the
      endoplasmic reticulum (ER) in muscle tissues. Cardiac SR membranes are
      specialized in the regulation of Ca(2+) transport and control of excitation
      contraction coupling. By contrast, the ER is responsible for protein synthesis,
      modification, secretion, lipid and steroid synthesis, and modulation of Ca(2+)
      signaling. Recent developments have indicated that functional changes in proteins
      or pathways normally associated with ER and not SR membrane impact cardiac
      development and pathology. Here, we propose that the SR and ER might be
      functionally distinct internal membrane compartments in cardiomyocytes.

PMID- 19409792
TI  - Pediatric multicentric glioma occurring after cranial irradiation.
AB  - An 8-year-old girl with no family history of neoplasia underwent biopsy and
      chemoradiation therapy for a suprasellar mixed germ cell tumor, which resulted in
      complete remission. A surveillance MRI taken 37 months after irradiation detected
      a non-enhancing mass in the genu of the corpus callosum. MRI taken 42 months
      after irradiation revealed significant growth of the mass and a new enhancing
      lesion in the temporal lobe, which showed rapid growth over 3 weeks. Subtotal
      resection and biopsy were performed on the lesions in the temporal lobe and the
      corpus callosum, respectively. Histological examination revealed that the
      temporal tumor was a glioblastoma multiforme and the frontal lesion was a diffuse
      astrocytoma. These tumors had newly developed within the irradiated field, but
      were separated in both location and time. Radiation-induced gliomas may develop
      within a shorter time interval than previously considered.

PMID- 19409793
TI  - Clinical and radiological findings and surgical management of ruptured aneurysms
      at the non-branching sites of the internal carotid artery.
AB  - Ruptured aneurysms located at the non-branching sites of the internal carotid
      artery, including blister-like aneurysms, possess unique clinical and technical
      features. This report presents nine consecutively managed patients with these
      types of aneurysm, detailing the clinical and radiological characteristics and
      surgical outcomes. The initial angiography identified aneurysmal lesions in six
      of the nine patients with two of these patients requiring additional three
      dimensional (3D) angiography. In three patients the aneurysm was only diagnosed
      on second or third angiograms. Six patients had blister-like aneurysms, and two
      had saccular-shaped aneurysms diagnosed on the basis of intraoperative findings.
      One patient with a saccular aneurysm died without surgery. Eight patients
      underwent a microsurgical procedure: clipping in five, clipping on wrapping with
      suturing in two and trapping in one. Three of these eight patients had an
      intraoperative rupture. A favorable outcome was obtained in seven patients.
      Advances in microsurgical techniques to prevent premature rupture and 3D
      radiological diagnosis with careful pre-operative consideration of the surgical
      strategies will be required for a further improvement of the clinical outcome.

PMID- 19409794
TI  - Superficial temporal artery-middle cerebral artery bypass for ischemic
      atherosclerotic middle cerebral artery disease.
AB  - Most recent studies on the effectiveness of cerebral revascularization have
      focused on the treatment of atherosclerotic internal carotid artery occlusive
      disease. The goal of the present study was to assess neurological function in 11
      severe atherosclerotic middle cerebral artery (MCA) disease patients with
      transient ischemic attacks (TIAs) and hemodynamic compromise and determine the
      efficacy of superficial temporal artery-middle cerebral artery (STA-MCA) bypass.
      There were eight patients with MCA occlusion and three with severe MCA stenosis.
      After the bypass procedure, all 11 patients experienced reduction in TIAs and no
      stroke during a mean follow-up of 34.36 months. Surgical revascularization
      increased regional cerebral blood flow (mL/100g/min) from a mean of (+/- standard
      deviation) 25.9+/-7.39 preoperatively to 32.3+/-7.72 postoperatively, and
      improved regional cerebrovascular reactivity from -6.42%+/-14.61% to 30.14%+/
      23.93% (p = 0.014) in the eight patients with atherosclerotic MCA occlusion. Our
      findings demonstrated the benefit of STA-MCA bypass for patients with medically
      refractory and symptomatic atherosclerotic MCA occlusion with hemodynamic
      compromise.

PMID- 19409795
TI  - Design, parallel synthesis, and crystal structures of biphenyl antithrombotics as
      selective inhibitors of tissue factor FVIIa complex. Part 1: Exploration of S2
      pocket pharmacophores.
AB  - Factor VIIa (FVIIa), a serine protease enzyme, coupled with tissue factor (TF)
      plays an important role in a number of thrombosis-related disorders. Inhibition
      of TF x FVIIa occurs early in the coagulation cascade and might provide some
      safety advantages over other related enzymes. We report here a novel series of
      substituted biphenyl derivatives that are highly potent and selective TF x FVIIa
      inhibitors. Parallel synthesis coupled with structure-based drug design allowed
      us to explore the S2 pocket of the enzyme active site. A number of compounds with
      IC(50) value of <10 nM were synthesized. The X-ray crystal structures of some of
      these compounds complexed with TF x FVIIa were determined and results were
      applied to design the next round of inhibitors. All the potent inhibitors were
      tested for inhibition against a panel of related enzymes and selectivity of
      17,600 over thrombin, 450 over trypsin, 685 over FXa, and 76 over plasmin was
      achieved. Two groups, vinyl 36b and 2-furan 36ab, were identified as the optimum
      binding substituents on the phenyl ring in the S2 pocket. Compounds with these
      two substituents are the most potent compounds in this series with good
      selectivity over related serine proteases. These compounds will be further
      explored for structure-activity relationship.

PMID- 19409797
TI  - 3D-QSAR studies of 2,2-diphenylpropionates to aid discovery of novel potent
      muscarinic antagonists.
AB  - Muscarinic acetylcholine receptors (mAChRs) consisting of five known subtypes,
      are widely distributed in both central and peripheral nervous systems for
      regulation of a variety of critical functions. The present theoretical study
      describes correlations between experimental and calculated molecular properties
      of 15 alpha-substituted 2,2-diphenylpropionate antimuscarinics using quantum
      chemical and pharmacophore generation methods to characterize the drug mAChR
      properties and design new therapeutics. The calculated stereoelectronic
      properties, such as total energies, bond distances, valence angles, torsion
      angles, HOMO-LUMO energies, reactivity indices, vibrational frequencies of ether
      and carbonyl moieties, and nitrogen atom proton affinity were found to be well
      correlated when compared with experimentally determined inhibition constants from
      the literature using three muscarinic receptor assays: [(3)H]NMS receptor
      binding, alpha-amylase release from rat pancreas, and guinea pig ileum
      contraction. In silico predicted toxicity on rat oral LD(50) values correlated
      well with the [(3)H]NMS binding in N4TG1 cells and alpha-amylase release assays,
      but not the ileum contraction assay. Next, to explore the functional requirements
      for potent activity of the compounds, we developed a preliminary 3D pharmacophore
      model using the in silico techniques. The resulting model contained a hydrogen
      bond acceptor site on the carbonyl oxygen atom and a ring aromatic feature on one
      of the two aromatic rings in these compounds. This model was used as a template
      to search an in-house database for novel analogs. We found compounds equal in
      inhibition potency to atropine and, importantly, six not reported before as
      antimuscarinics. These results demonstrate that this QSAR approach not only
      provides a basis for understanding the molecular mechanism of action but a
      pharmacophore to aid in the discovery and design of novel potent muscarinic
      antagonists.

PMID- 19409796
TI  - Design, synthesis and evaluations of acridone derivatives using Candida albicans-
      search for MDR modulators led to the identification of an anti-candidiasis agent.
AB  - In order to search for MDR modulators, rationally designed acridone derivatives
      were investigated for their effect on influx or efflux of Rhodamine6G (R6G) in
      CAI4 cells. Results of these investigations indicate that in presence of compound
      12, inhibition of growth of CAI4 cells and also an increased influx/efflux of R6G
      in CAI4 cells have been observed. This seems to be occurring due to the cell wall
      rupturing of Candida albicans. Compound 12 may be a suitable candidate for
      candidiasis therapy.

PMID- 19409798
TI  - Neutron spectra measurement and comparison of the HFR and THOR BNCT beams.
AB  - This paper aims to measure the spectra of HB11 (high flux reactor, HFR) and the
      Tsing Hua open-pool reactor (THOR) boron neutron capture therapy (BNCT) beams by
      multiple activation foils. The self-shielding corrections were made with the aid
      of MCNP calculations. The initial spectra were adjusted by a sophisticated
      process named coarse-scaling adjustment using SAND-EX, which can adjust a given
      coarse-group spectrum into a fine-group structure, i.e. 640 groups, with
      excellent continuity. The epithermal neutron flux of the THOR beam is about three
      times of HB11. The thermal neutron flux, boron and gold reaction rates along the
      central axis of a PMMA phantom are calculated for both adjusted spectra for
      comparison.

PMID- 19409799
TI  - Effectiveness of boron neutron capture therapy for recurrent head and neck
      malignancies.
AB  - It is necessary to explore new treatments for recurrent head and neck
      malignancies (HNM) to avoid severe impairment of oro-facial structures and
      functions. Boron neutron capture therapy (BNCT) is tumor-cell targeted
      radiotherapy that has significant superiority over conventional radiotherapies in
      principle. We have treated with BNCT 42 times for 26 patients (19 squamous cell
      carcinomas (SCC), 4 salivary gland carcinomas and 3 sarcomas) with a recurrent
      and far advanced HNM since 2001. Results of (1) (10)B concentration of
      tumor/normal tissue ratios (T/N ratio) of FBPA-PET studies were SCC: 1.8-5.7,
      sarcoma: 2.5-4.0, parotid tumor: 2.5-3.7. (2) Therapeutic effects were CR: 12
      cases, PR: 10 cases, PD: 3 cases NE (not evaluated): 1 case. Response rate was
      85%. (3) Improvement of QOL such as a relief of severe pain, bleeding, and
      exudates at the local lesion, improvement of PS, disappearance of ulceration,
      covered with normal skin and preserved oral and maxillofacial functions and
      tissues. (4) Survival periods after BNCT were 1-72 months (mean: 13.6 months).
      Six-year survival rate was 24% by Kaplan-Meier analysis. (5) Adverse-events were
      transient mucositis and alopecia in most of the cases; three osteomyelitis and
      one brain necrosis were recognized. These results indicate that BNCT represents a
      new and promising treatment approach for advanced HNM.

PMID- 19409800
TI  - Characterization and expression analysis of AGAMOUS-like, SEEDSTICK-like, and
      SEPALLATA-like MADS-box genes in peach (Prunus persica) fruit.
AB  - MADS-box genes encode transcriptional regulators that are critical for flowering,
      flower organogenesis and plant development. Although there are extensive reports
      on genes involved in flower organogenesis in model and economically important
      plant species, there are few reports on MADS-box genes in woody plants. In this
      study, we have cloned and characterized AGAMOUS (AG), SEEDSTICK (STK) and
      SEPALLATA (SEP) homologs from peach tree (Prunus persica L. Batsch) and studied
      their expression patterns in different tissues as well as in fruit pericarp
      during pit hardening. AG- STK- and SEP-like homologs, representative of the C-, D
      , E-like MADS-box gene lineages, respectively, play key roles in stamen, carpel,
      ovule and fruit development in Arabidopsis thaliana. Sequence similarities,
      phylogenetic analysis and structural characteristics were used to provide
      classification of the isolated genes in type C (PPERAG), type D (PPERSTK) and
      type E (PPERSEP1, PPERSEP3, PPERFB9) organ identity genes. Expression patterns
      were determined and in combination with phylogenetic data provided useful
      indications on the function of these genes. These data suggest the involvement of
      MADS-box genes in peach flower and fruit development and provide further evidence
      for the role of these genes in woody perennial trees that is compatible with
      their function in model plant species.

PMID- 19409801
TI  - Risk factors analysis on failure of maze procedure: mid-term results.
AB  - OBJECTIVE: Since the late 1980s, surgical ablation of atrial fibrillation (AF)
      has been one of the most effective means of curing this arrhythmia. However,
      about 20% of patients who underwent maze procedures have shown recurrence of AF
      during the follow-up periods. The aim of this study is to evaluate our result of
      maze procedures in last decade and to analyze the risk factors of maze failure.
      METHODS: Between July 1997 and July 2007, 560 consecutive patients underwent maze
      procedures for AF by a single surgeon. Demographics showed that average age of
      the patients is 51.3 years, with a slight female predominance (M:F = 248:312).
      Most of the maze procedures had been performed in conjunction with mitral valve
      (n = 494, 88.6%), while only six cases (1.1%) were performed with isolated maze
      procedure. The maze failure was defined as showing any rhythm besides normal
      sinus rhythm at the last follow-up. Univariate and multivariate analysis for the
      risk factors of maze failure were identified. The survival impact of maze failure
      was also evaluated. RESULTS: The in-hospital mortality (1.6%) was acceptable.
      During the 29.7 months of median follow-up period, the late mortality rate was
      3.8% and permanent pacemaker insertion was necessary in 2.3% (n = 13) of the
      patients. The success rate of maze was 84.1% (471/560) and effective left atrial
      contraction was identified in 97.2% (458/471) of these patients. In multivariate
      analysis, the size of left atrium larger than 60 mm, cardiothoracic ratio over
      60%, fine AF wave in preoperative ECG, no early normal sinus restoration and
      simplified surgical ablation were found as an independent predictor of maze
      failure. Furthermore, the patients with successful maze showed better long-term
      survival rates. CONCLUSIONS: The results of our maze procedure during the last
      decade showed an acceptable success rate and the patients who were restored to
      sinus rhythm after maze procedures showed better long-term survival rates. For
      the patients who have independent biological risk factors, more thorough ablation
      lesion set is recommended for better long-term results.

PMID- 19409802
TI  - Toward quality improvement of thoracic aortic surgery: estimating volume-outcome
      effect from nationwide survey.
AB  - BACKGROUND: Although understanding the association between surgical volume and
      outcome has been the focus of much research, no study has yet reported the volume
      outcome effect for thoracic aortic surgery. METHODS: From the clinical database,
      we identified and analyzed 2875 procedures that took place across 36 centers
      between 2003 and 2005. The effect of hospital procedural volume was assessed for
      each outcome measure using a hierarchical mixed-effects logistic regression
      model. Clinical risk factors, procedural year, clinical processes, range of
      replacement, hospital volume and surgeon volume were set as fixed effects and
      sites were used as random intercepts. RESULTS: The logistic regression model
      revealed that hospital thoracic aortic surgery volume was linked to statistically
      significant decreases in both 30-day mortality (p=0.127: OR 0.988-0.999) and
      operative mortality (p=0.022: 0.989-0.999). In addition, subgroup analysis showed
      that increased hospital volume was associated with reduced mortality rates in
      patients under 65 years of age (p=0.038: 0.982-0.999) and in high-risk surgical
      candidates (p=0.019: 0.989-0.999). Thoracic aortic surgery volume of surgeons,
      hospital adult cardiovascular surgery volume and surgeons adult cardiovascular
      surgery volume did not significantly impact these outcomes. CONCLUSIONS: In this
      study higher annual hospital thoracic aortic surgery volume of hospitals is
      associated with reduced mortality rates for thoracic aortic surgery. In Japan it
      is not the hospital general adult cardiovascular surgery volume, but the hospital
      specific thoracic aortic surgery volume that might be preferable for quality
      indicator of thoracic aortic surgery.

PMID- 19409803
TI  - Vasoplegic syndrome after off-pump coronary artery bypass surgery: a rising
      threat.

PMID- 19409804
TI  - A rare coronary anomaly detected by computed tomography angiography: the left
      circumflex artery originating from the descending thoracic aorta.

PMID- 19409807
TI  - In vitro phototoxic activity of Eugenia jambolana L. and Hyptis martiusii Benth.
AB  - Ethanol extracts from Hyptis martiusii and Eugenia jambolana were assayed for
      light-mediated activity against strains of Staphylococcus aureus, Escherichia
      coli and Pseudomonas aeruginosa. Duplicate assays were conducted with and without
      exposure to UV-A radiation to test for light-activated or light-enhanced
      activity. Both extracts showed activity against at least two bacterial strains,
      but H. martiusii was the most active extract, being active against all strains of
      S. aureus and E. coli. The results represent a first report of the light-mediated
      antimicrobial activities of H. martiusii and E. jambolana and suggest that
      phytochemical investigations may be warranted.

PMID- 19409805
TI  - A new self-expanding aortic stent valve with annular fixation: in vitro
      haemodynamic assessment.
AB  - OBJECTIVE: Balloon-expandable stent valves require flow reduction during
      implantation (rapid pacing). The present study was designed to compare a self
      expanding stent valve with annular fixation versus a balloon-expandable stent
      valve. METHODS: Implantation of a new self-expanding stent valve with annular
      fixation (Symetis, Lausanne, Switzerland) was assessed versus balloon-expandable
      stent valve, in a modified Dynatek Dalta pulse duplicator (sealed port access to
      the ventricle for transapical route simulation), interfaced with a computer for
      digital readout, carrying a 25 mm porcine aortic valve. The cardiovascular
      simulator was programmed to mimic an elderly woman with aortic stenosis: 120/85
      mmHg aortic pressure, 60 strokes/min (66.5 ml), 35% systole (2.8 l/min). RESULTS:
      A total of 450 cardiac cycles was analysed. Stepwise expansion of the self
      expanding stent valve with annular fixation (balloon-expandable stent valve)
      resulted in systolic ventricular increase from 120 to 121 mmHg (126 to 830+/-76
      mmHg)*, and left ventricular outflow obstruction with mean transvalvular gradient
      of 11+/-1.5 mmHg (366+/-202 mmHg)*, systolic aortic pressure dropped distal to
      the valve from 121 to 64.5+/-2 mmHg (123 to 55+/-30 mmHg) N.S., and output
      collapsed to 1.9+/-0.06 l/min (0.71+/-0.37 l/min* (before complete obstruction)).
      No valve migration occurred in either group. (*=p<0.05). CONCLUSIONS:
      Implantation of this new self-expanding stent valve with annular fixation has
      little impact on haemodynamics and has the potential for working heart
      implantation in vivo. Flow reduction (rapid pacing) is not necessary.

PMID- 19409808
TI  - Radiobiological basis and clinical results of the simultaneous integrated boost
      (SIB) in intensity modulated radiotherapy (IMRT) for head and neck cancer: A
      review.
AB  - The simultaneous integrated boost (SIB)-IMRT technique allows the simultaneous
      delivery of different dose levels to different target volumes within a single
      treatment fraction. The most significant aspect associated with SIB-IMRT is
      related to the fractionation strategy, concerning two time-dose parameters: (1)
      the shortening of the overall treatment time (OTT); (2) the increase of fraction
      size (FS) to the boost volume. The SIB-IMRT technique represents, therefore, a
      new way to investigate the accelerated fractionation in definitive treatment of
      head and neck (H&N) cancers. The aims of this paper are the following: (1) to
      briefly review the influence of OTT and FS on H&N tumors and on acutely and late
      responding normal tissues; (2) to review the results of clinical studies of
      accelerated radiotherapy not employing IMRT in H&N cancer; (3) to review the
      clinical experiences of the SIB-IMRT technique and to compare the different SIB
      regimes in terms of radiobiological efficacy.

PMID- 19409809
TI  - Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth
      factor (CCN2) as prognostic markers for progression of diabetic nephropathy.
AB  - Profibrotic growth factors and inflammatory chemokines have been implicated in
      the pathogenesis of diabetic nephropathy (DN). However, measurement of urinary
      monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor
      (CCN2) as prognostic markers has not previously been reported, and neither have
      two such molecules in urine been examined in a single study of DN. In this
      prospective observational study, 43 adult diabetic patients were studied, 40 were
      followed up for 6years. Urinary MCP-1/creatinine ratios were found to be
      significantly higher in patients with macroalbuminuria (3.3- and 2.1-fold higher
      (p<0.01) than normoalbuminuric and microalbuminuric patients, respectively). CCN2
      exhibited a pattern different from that of urinary MCP-1. Urinary CCN2/creatinine
      ratios were greatly elevated in both microalbuminuric and macroalbuminuric
      patients (125- and 74-fold higher than normoalbuminuric patients, respectively,
      p<0.01 and p<0.05, respectively). Further, urinary CCN2, but not MCP-1,
      correlated with progression of microalbuminuria (R=0.49, p<0.05). In contrast,
      MCP-1, but not CCN2, correlated with the rate of eGFR decline for all patients
      (R=0.61, p<0.0001), reflective of its predictive value in patients with
      macroalbuminuria, but not for patients with microalbuminuria or normoalbuminuria.
      In conclusion, increased urinary CCN2 is associated with the early progression of
      DN, whereas MCP-1 is associated with later stage disease.

PMID- 19409811
TI  - Development of quadrupole mass spectrometers using rapid prototyping technology.
AB  - In this report, we present a prototype design of a quadrupole mass filter (QMF)
      with hyperbolic electrodes, fabricated at the University of Liverpool using
      digital light processing (DLP), a low-cost and lightweight 3D rapid prototyping
      (RP) technique. Experimental mass spectra are shown for H(2)(+), D(2)(+), and
      He(+) ions to provide proof of principle that the DLP mass filter is working as a
      mass analyzer in the low-mass range (1 to 10 amu). The performance of the DLP QMF
      has also been investigated for individual spectral peaks. Numerical simulations
      of the instrument were performed by coupling CPO and Liverpool QMS-2 programs to
      model both the ion source and mass filter, respectively, and the instrument is
      shown to perform as predicted by theory. DLP thus allows miniaturization of mass
      spectrometers at low cost, using hyperbolic (or other) geometries of mass
      analyzer electrodes that provide optimal ion manipulation and resolution for a
      given application. The potential of using RP fabrication techniques for
      developing miniature and microscale mass analyzers is also discussed.

PMID- 19409810
TI  - Mass measurement and top-down HPLC/MS analysis of intact monoclonal antibodies on
      a hybrid linear quadrupole ion trap-Orbitrap mass spectrometer.
AB  - Mass and top-down analyses of 150-kDa monoclonal immunoglobulin gamma (IgG)
      antibodies were performed on an Orbitrap analyzer. Three different sample
      delivery methods were tested including (1) infusion of an off-line desalted IgG
      sample using nano-electrospray; (2) on-line desalting followed by a step elution
      with a high percentage of organic solvent; and (3) reversed-phase HPLC separation
      and on-line mass and top-down analyses of disulfide isoforms of an IgG2 antibody.
      The accuracy of mass measurements of intact antibody was within +/-2 Da (15 ppm).
      The glycoforms of intact IgG antibodies separated by 162 Da were baseline
      resolved. In-source fragmentation of the intact antibodies produced mainly 115
      residue fragments including N-terminal variable domains of heavy and light
      chains. The sequence coverage (the number of cleavages) was greatly increased
      after reduction of disulfide bonds and HPLC/MS/MS analysis of light and heavy
      chains using collision-induced dissociation in the ion trap of the LTQ-Orbitrap.
      This is an attractive alternative to peptide mapping for characterization and
      monitoring of post-translational modifications attributed to minimal sample
      preparation, high speed of the mass/top-down analysis, and relatively minor
      method-induced sample modifications.

PMID- 19409812
TI  - Identification and integration of sensory modalities: neural basis and relation
      to consciousness.
AB  - A key question in studying consciousness is how neural operations in the brain
      can identify streams of sensory input as belonging to distinct modalities, which
      contributes to the representation of qualitatively different experiences. The
      basis for identification of modalities is proposed to be constituted by self
      organized comparative operations across a network of unimodal and multimodal
      sensory areas. However, such network interactions alone cannot answer the
      question how sensory feature detectors collectively account for an integrated,
      yet phenomenally differentiated experiential content. This problem turns out to
      be different from, although related to, the binding problem. It is proposed that
      the neural correlate of an enriched, multimodal experience is constituted by the
      attractor state of a dynamic associative network. Within this network, unimodal
      and multimodal sensory maps continuously interact to influence each other's
      attractor state, so that a feature change in one modality results in a fast re
      coding of feature information in another modality. In this scheme, feature
      detection is coded by firing-rate, whereas firing phase codes relational aspects.

PMID- 19409813
TI  - Identifying depression in epilepsy in a busy clinical setting is enhanced with
      systematic screening.
AB  - PURPOSE: Depression is a highly prevalent, relatively underdiagnosed and
      undertreated comorbid condition in epilepsy. The purpose of this study was to
      determine the effect of using a validated self-reporting depression scale on the
      ability to detect depression in people with epilepsy receiving care in a busy
      clinical setting. METHODS: The Neurological Disorders Depression Inventory for
      Epilepsy (NDDI-E) is a 6-item questionnaire validated to screen for depression in
      people with epilepsy. We performed a retrospective chart review of 192
      consecutive patients who had completed the NDDI-E while receiving care at a
      seizure clinic in the largest public hospital in Houston, Texas. For comparison,
      charts of 192 consecutive patients receiving care immediately prior to the
      implementation of the NDDI-E in the same clinic were assessed. RESULTS: Fifty
      five (28.6%) of patients screened positive for depression with the NDDI-E. They
      subsequently received a semi-structured psychiatric interview based on the DSM-IV
      model and 89% (n=49) were confirmed to have major depression. Use of the NDDI-E
      thus resulted in the detection of active depression in 25.5% (n=49) of the
      patients, whereas only 2.6% (n=5) of patients in the group not systematically
      screened were found to have active depression (p<0.0001). Thirty-two of the 49
      (65%) patients with depression detected by screening were not previously
      diagnosed or treated. Multivariate analysis revealed that a history of
      depression, seizure frequency, and topiramate use were independent predictors of
      depression. Lamotrigine use was protective against depression. DISCUSSION: Use of
      the NDDI-E significantly improved the ability to detect depression in epilepsy
      patients in a busy clinical practice.

PMID- 19409814
TI  - NKAP is a transcriptional repressor of notch signaling and is required for T cell
      development.
AB  - T cell development depends on the coordinated interplay between receptor
      signaling and transcriptional regulation. Through a genetic complementation
      screen a transcriptional repressor, NKAP, was identified. NKAP associated with
      the histone deacetylase HDAC3 and was shown to be part of a DNA-binding complex,
      as demonstrated by chromatin immunoprecipitation. NKAP also associated with the
      Notch corepressor complex. The expression of NKAP during T cell development
      inversely correlated with the expression of Notch target genes, implying that
      NKAP may modulate Notch-mediated transcription. To examine the function of NKAP
      in T cell development, we ablated NKAP by Lck(cre). Loss of NKAP blocked
      development of alphabeta but not gammadelta T cells, and Nkap(fl/o)Lck(cre) DP T
      cells expressed 8- to 20-fold higher amounts of Hes1, Deltex1, and CD25 mRNA.
      Thus, NKAP functions as a transcriptional repressor, acting on Notch target
      genes, and is required for alphabeta T cell development.

PMID- 19409816
TI  - Sequential polarization and imprinting of type 1 T helper lymphocytes by
      interferon-gamma and interleukin-12.
AB  - Differentiation of naive T lymphocytes into type I T helper (Th1) cells requires
      interferon-gamma and interleukin-12. It is puzzling that interferon-gamma induces
      the Th1 transcription factor T-bet, whereas interleukin-12 mediates Th1 cell
      lineage differentiation. We use mathematical modeling to analyze the expression
      kinetics of T-bet, interferon-gamma, and the IL-12 receptor beta2 chain (IL
      12Rbeta2) during Th1 cell differentiation, in the presence or absence of
      interleukin-12 or interferon-gamma signaling. We show that interferon-gamma
      induced initial T-bet expression, whereas IL-12Rbeta2 was repressed by T cell
      receptor (TCR) signaling. The termination of TCR signaling permitted upregulation
      of IL-12Rbeta2 by T-bet and interleukin-12 signaling that maintained T-bet
      expression. This late expression of T-bet, accompanied by the upregulation of the
      transcription factors Runx3 and Hlx, was required to imprint the Th cell for
      interferon-gamma re-expression. Thus initial polarization and subsequent
      imprinting of Th1 cells are mediated by interlinked, sequentially acting positive
      feedback loops of TCR-interferon-gamma-Stat1-T-bet and interleukin-12-Stat4-T-bet
      signaling.

PMID- 19409815
TI  - Guanine nucleotide-binding proteins of the G12 family shape immune functions by
      controlling CD4+ T cell adhesiveness and motility.
AB  - Integrin-mediated adhesion plays a central role in T cell trafficking and
      activation. Genetic inactivation of the guanine nucleotide-binding (G) protein
      alpha-subunits Galpha(12) and Galpha(13) resulted in an increased activity of
      integrin leukocyte-function-antigen-1 in murine CD4(+) T cells. The interaction
      with allogeneic dendritic cells was enhanced, leading to an abnormal
      proliferative response in vitro. In vivo, T cell-specific inactivation of
      Galpha(12) and Galpha(13) caused lymphadenopathy due to increased lymph node
      entry and enhanced T cell proliferation, and the susceptibility toward T cell
      mediated diseases was enhanced. Mechanistically, we show that in the absence of
      Galpha(12) and Galpha(13) the activity of the small GTPases Rac1 and Rap1 was
      increased, whereas signaling of the small GTPase RhoA was strongly reduced. Our
      data indicate that locally produced mediators signal through Galpha(12)- and
      Galpha(13)-coupled receptors to negatively regulate cell polarization and
      adhesiveness, thereby fine-tuning T cell trafficking, proliferation, and
      susceptibility toward T cell-mediated diseases.

PMID- 19409818
TI  - Volumetric measurement pulmonary ground-glass opacity nodules with multi-detector
      CT: effect of various tube current on measurement accuracy--a chest CT phantom
      study.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the effect of
      various tube currents on the accuracy of volumetric measurements of ground-glass
      opacity (GGO) nodules using a chest phantom. MATERIALS AND METHODS: A chest
      phantom containing 13 artificial GGO nodules with known volumes was scanned using
      a 64-slice computed tomographic scanner at different tube currents (30, 60, 90,
      120, 150, 180, and 210 mA). Volumetric measurements were performed using
      software. The relative percentage error and the absolute percentage error between
      the volume measures on computed tomography and the reference-standard volumes
      were calculated. Correlations between the mean absolute percentage error and the
      mean attenuation of nodules and between the ratio of solid component and the mean
      attenuation of nodules were analyzed. RESULTS: The relative percentage errors
      showed that there was substantial underestimation of nodule volumes at 30, 60,
      and 90 mA and substantial overestimation of volumes at 120, 150, 180, and 210 mA,
      but there was no statistically significant difference in absolute percentage
      errors (P = .876). Pearson's correlation coefficient of the mean absolute
      percentage errors of nodules on volumetric measurement versus the mean
      attenuation value of nodules showed a negative correlation, and the ratio of
      solid component to whole nodule versus the mean attenuation of nodules showed a
      positive correlation. CONCLUSION: Volume measurement is a promising method for
      the quantification of GGO nodule volume. It is important to know that different
      tube currents can affect the accuracy of volumetric measurements.

PMID- 19409817
TI  - Prediction of malignant breast lesions from MRI features: a comparison of
      artificial neural network and logistic regression techniques.
AB  - RATIONALE AND OBJECTIVES: Dynamic contrast-enhanced magnetic resonance imaging is
      a clinical imaging modality for the detection and diagnosis of breast lesions.
      Analytic methods were compared for diagnostic feature selection and the
      performance of lesion classification to differentiate between malignant and
      benign lesions in patients. MATERIALS AND METHODS: The study included 43
      malignant and 28 benign histologically proved lesions. Eight morphologic
      parameters, 10 gray-level co-occurrence matrix texture features, and 14 Laws
      texture features were obtained using automated lesion segmentation and
      quantitative feature extraction. Artificial neural network (ANN) and logistic
      regression analysis were compared for the selection of the best predictors of
      malignant lesions among the normalized features. RESULTS: Using ANN, the final
      four selected features were compactness, energy, homogeneity, and Law_LS, with an
      area under the receiver-operating characteristic curve (AUC) of 0.82 and accuracy
      of 0.76. The diagnostic performance of these four features computed on the basis
      of logistic regression yielded an AUC of 0.80 (95% confidence interval [CI],
      0.688-0.905), similar to that of ANN. The analysis also showed that the odds of a
      malignant lesion decreased by 48% (95% CI, 25%-92%) for every increase of 1
      standard deviation in the Law_LS feature, adjusted for differences in
      compactness, energy, and homogeneity. Using logistic regression with z-score
      transformation, a model composed of compactness, normalized radial length
      entropy, and gray-level sum average was selected, and it had the highest overall
      accuracy, 0.75, among all models, with an AUC of 0.77 (95% CI, 0.660-0.880). When
      logistic modeling of transformations using the Box-Cox method was performed, the
      most parsimonious model with predictors compactness and Law_LS had an AUC of 0.79
      (95% CI, 0.672-0.898). CONCLUSION: The diagnostic performance of models selected
      by ANN and logistic regression was similar. The analytic methods were found to be
      roughly equivalent in terms of predictive ability when a small number of
      variables were chosen. The robust ANN methodology uses a sophisticated nonlinear
      model, while logistic regression analysis provides insightful information to
      enhance the interpretation of the model features.

PMID- 19409819
TI  - Three dimensional assessment of knee cartilage in cadavers with high resolution
      MR-arthrography and MSCT-arthrography.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to compare high-resolution
      magnetic resonance (MR) arthrography and multislice computed tomographic (MSCT)
      arthrography in the evaluation of the entire knee cartilage obtained from
      cadavers. MATERIALS AND METHODS: MR arthrography and MSCT arthrography were
      performed on 16 cadaver knees, and their findings were compared to those found
      during macroscopic assessment. The sensitivity and specificity of MR arthrography
      and MSCT arthrography for detecting cartilage lesions of grade > or = 2 and
      Spearman's correlation coefficients between arthrographic and macroscopic grades
      were determined. In addition, cartilage surface conspicuity of the two techniques
      was measured using a subjective ranking system. RESULTS: The sensitivity and
      specificity, respectively, for the detection of cartilage disorder (grade > or =
      2) were 87% and 97% on MR arthrography and 84% and 99% on MSCT arthrography.
      There was no statistically significant difference between the two techniques in
      sensitivity (P = 1.000) or specificity (P = .625). Spearman's correlation
      coefficients between MR arthrography or MSCT arthrography and macroscopic grading
      were 0.783 and 0.800, respectively, with no statistically difference (P = .492).
      Both MR arthrography and MSCT arthrography enabled the accurate depiction of
      cartilage surface. CONCLUSIONS: High-resolution MR arthrography and MSCT
      arthrography were comparably accurate for the assessment of cartilage lesions of
      the entire knee.

PMID- 19409820
TI  - Effect of automatic tube current modulation on radiation dose and image quality
      for low tube voltage multidetector row CT angiography: phantom study.
AB  - RATIONALE AND OBJECTIVES: To evaluate the effect of automatic tube current
      modulation on radiation dose and image quality for low tube voltage computed
      tomography (CT) angiography. MATERIALS AND METHODS: An anthropomorphic phantom
      was scanned with a 64-section CT scanner using following tube voltages: 140 kVp
      (Protocol A), 120 kVp (Protocol B), 100 kVp (Protocol C), and 80 kVp (Protocol
      D). To achieve similar noise, combined z-axis and xy-axes automatic tube current
      modulation was applied. Effective dose (ED) for the four tube voltages was
      assessed. Three plastic vials filled with different concentrations of iodinated
      solution were placed on the phantom's abdomen to obtain attenuation measurements.
      The signal-to-noise ratio (SNR) was calculated and a figure of merit (FOM) for
      each iodinated solution was computed as SNR(2)/ED. RESULTS: The ED was kept
      similar for the four different tube voltages: (A) 5.4 mSv +/- 0.3, (B) 4.1 mSv +/
      0.6, (C) 3.9 mSv +/- 0.5, and (D) 4.2 mSv +/- 0.3 (P > .05). As the tube voltage
      decreased from 140 to 80 kVp, image noise was maintained (range, 13.8-14.9 HU) (P
      > .05). SNR increased as the tube voltage decreased, with an overall gain of 119%
      for the 80-kVp compared to the 140-kVp protocol (P < .05). The FOM results
      indicated that with a reduction of the tube voltage from 140 to 120, 100, and 80
      kVp, at constant SNR, ED was reduced by a factor of 2.1, 3.3, and 5.1,
      respectively, (P < .001). CONCLUSIONS: As tube voltage decreases, automatic tube
      current modulation for CT angiography yields either a significant increase in
      image quality at constant radiation dose or a significant decrease in radiation
      dose at a constant image quality.

PMID- 19409821
TI  - Condyle replacement after tumor resection: comparison of individual prefabricated
      titanium implants and costochondral grafts.

PMID- 19409822
TI  - Hematologic characterization and chromosomal localization of the novel dominantly
      inherited mouse hemolytic anemia, neonatal anemia (Nan).
AB  - One of the most commonly inherited anemias in man is Hereditary Spherocytosis
      (HS) with an incidence of 1 in 2000 for persons of Northern European descent.
      Mouse models of HS include spontaneous inherited hemolytic anemias and those
      generated by gene targeting. The Neonatal anemia (Nan) mouse is a novel model of
      HS generated by N-ethyl-N-nitrosurea mutagenesis and suffers from a severe
      neonatal anemia. Adult Nan mice have a lifelong hemolytic anemia with decreased
      red blood cell numbers, hematocrit, and hemoglobin, but elevated zinc
      protoporphyrin levels. Blood smears taken from Nan mice show a hypochromic anemia
      characterized by poikilocytosis, anisocytosis and polychromasia. The Nan
      phenotype can be transferred by bone marrow transplantation indicating that the
      defect is intrinsic to bone marrow. The hemolytic anemia in adult Nan mice can be
      identified by osmotic fragility testing. Examination of the erythrocyte membrane
      skeleton proteins (EMS) reveals a global deficiency of these proteins with
      protein 4.1a being completely absent. The Nan locus maps to mouse Chromosome 8
      and does not co-localize with any known EMS genes. The identification of the Nan
      gene will likely uncover a novel protein that contributes to the stability of the
      EMS and may identify a new mutation for HS.

PMID- 19409824
TI  - Use of a phospholipase-C assay, in vivo pathogenicity assays and PCR in assessing
      the virulence of Listeria spp.
AB  - Listeria spp. was isolated from 19.8% of animals with a history of reproductive
      disorders. A total of 333 faecal, genital swab and blood samples from 111 animals
      (cattle, buffaloes, sheep and goats) were subjected to PCR to detect virulence
      associated genes (prfA, plcA, hlyA, actA and iap) and pathogenicity testing by
      the phosphatidylinositol phospholipase-C (PI-PLC) assay, and by mouse and chick
      embryo inoculation. One isolate of Listeria ivanovii recovered from a genital
      swab from a sheep was found to be pathogenic. Virulence assessment was then
      carried out on two L. ivanovii and 29 Listeria monocytogenes isolates from
      various sources using these assays. Haemolytic L. monocytogenes isolates lacking
      the plcA gene and PI-PLC activity were deemed non-pathogenic when assessed by
      mouse and chick embryo inoculation tests, in spite of having the hlyA gene. The
      results suggested that the PI-PLC and PCR assays are reliable in vitro
      alternatives to in vivo pathogenicity tests for L. monocytogenes.

PMID- 19409823
TI  - Biology of bovine herpesvirus 5.
AB  - Bovine herpesvirus 5 (BoHV-5) is an alphaherpesvirus responsible for
      meningoencephalitis in young cattle and is closely antigenically and genetically
      related to bovine herpesvirus 1 (BoHV-1). Both viruses have common aspects in
      their pathogenesis: (1) they infect epithelial cells at the portal of entry and
      (2) they establish a latent infection in the sensory nerve ganglia, i.e., the
      trigeminal ganglia. However, they have different neuroinvasion and neurovirulence
      capacities. Only in rare cases can BoHV-1 reach the brain of infected cattle.
      BoHV-5 infection induces different degrees of severity of neurological disease
      depending on both viral and host factors. Although a case of BoHV-5 associated
      disease in Europe and some outbreaks in USA and Australia have been reported, the
      current geographical distribution of BoHV-5 infection is mainly restricted to
      South America, especially Brazil and Argentina. This review focuses on the
      genomic characteristics, pathobiology and epidemiology of BoHV-5, in order to
      provide information on the possible basis of alphaherpesvirus neuropathogenesis.

PMID- 19409825
TI  - Magnetization transfer magic-angle-spinning z-spectroscopy of excised tissues.
AB  - NMR experiments devised to aid in analyses of tissues include magnetization
      transfer (MT), which can highlight the signals of biological macromolecules
      through cross-relaxation and/or chemical exchange processes with the bulk (1)H
      water resonance, and high-resolution magic-angle-spinning (HRMAS) methods, akin
      to those used in solid-state NMR to introduce additional spectral resolution via
      the averaging of spin anisotropies. This paper explores the result of combining
      these methodologies, and reports on MT "z-spectroscopy" between water and cell
      components in excised tissues under a variety of HRMAS conditions. Main features
      arising from the resulting (1)H "MTMAS" experiments include strong spinning
      sideband manifolds centered at the liquid water shift, high-resolution isotropic
      features coinciding with aliphatic and amide proton resonances, and a second
      sideband manifold arising as spinning speeds are increased. Interpretations are
      given for the origin of these various features, including simulations shedding
      further light onto the nature of MT NMR signals observed for tissue samples.
      Concurrently, histological examinations are reported validating the limits of
      HRMAS NMR procedures to the analysis of tissue samples preserved in a number of
      different ways.

PMID- 19409827
TI  - [Immune thrombocytopenic purpura: pathophysiology and treatment].
AB  - Immune thrombopenic purpura (ITP) is an autoimmune disease characterized by a
      peripheral destruction of platelets. B lymphocytes play a key role but
      pathophysiology is more complex, involving humoral and cellular immunity
      associated with an inappropriate platelet production. The treatment of ITP is
      still based on uncontrolled studies. Prednisone and intravenous immunoglobulins
      remain the first line treatments. Splenectomy remains the best "curative"
      treatment for adults with chronic ITP. However, most patients are reluctant to
      undergo surgery and new treatments give promising results. Among them, rituximab
      and thrombopoietin receptor agonists could replace splenectomy in near future.

PMID- 19409826
TI  - An outbreak of Crimean-Congo hemorrhagic fever in western Anatolia, Turkey.
AB  - OBJECTIVE: Sporadic Crimean-Congo hemorrhagic fever (CCHF) cases were first
      reported in Turkey in 2002, arising particularly in northeastern Anatolia.
      Epidemics have been reported in neighboring countries since the 1970s. With the
      increase in number of CCHF virus infected or suspected cases in the Aydin region
      of western Anatolia by 2006, we decided to focus attention on this disease.
      METHODS: Twenty-six patients with an acute febrile syndrome characterized by
      malaise, bleeding, leukopenia, and thrombocytopenia were admitted to various
      hospitals in Aydin between May 2007 and June 2008. CCHF diagnosis was established
      by measuring IgM in a blood sample and/or detecting viral genome by real-time
      polymerase chain reaction (real-time PCR) or by clinical findings of the disease,
      even if IgM was negative (real-time PCR was not performed). RESULTS: Twenty-five
      patients (22 of the patients with cases confirmed by laboratory findings) matched
      the criteria for CCHF defined by the European Network for Diagnostics of
      'Imported' Viral Diseases (ENIVD); one patient did not match suspected-case
      criteria, however he was also included in the study as his blood sample was
      positive according to real-time PCR. The most common signs and symptoms
      encountered were fever, myalgia, nausea, and vomiting. The overall case-fatality
      rate was 5.5% (one patient) in 2007. Patients showed hemorrhagic manifestations
      (35%), while complete blood counts revealed thrombocytopenia and leukopenia in 17
      patients (65%), and raised levels of aspartate aminotransferase (77%), alanine
      aminotransferase (77%), lactate dehydrogenase (69%), and creatinine phosphokinase
      (42%). CONCLUSIONS: To date, western Anatolia has been accepted as a non-endemic
      area for this disease, with only sporadic cases. These non-endemic CCHF cases in
      Aydin province of the Aegean region should alert other non-endemic regions of the
      world to be mindful of this disease.

PMID- 19409828
TI  - [Fetal and neonatal alloimmune thrombocytopenias].
AB  - Fetal and neonatal alloimmune thrombocytopenias result from maternal immunization
      against fetal specific platelet antigens inherited from the father that the
      mother lacks. The incidence has been estimated to one in 800 to one in 1000 live
      births. The most feared complication in case of severe thrombocytopenia is the
      occurrence of intracranial hemorrhage, leading to death or neurological sequelea.
      The diagnosis is straightforward when a maternal alloantibody is detected and the
      offending antigen identified in the infant. Any difficulties in confirming the
      diagnosis should not delay the treatment. Since the first description of these
      conditions in the 1950's, significant progress has been made in laboratory
      diagnosis and management.

PMID- 19409829
TI  - [Genotyping applied to platelet immunology: when? How? Limits].
AB  - Platelet alloantigens named Human Platelet Antigens (HPA) are involved in immune
      conflicts such as post-transfusion purpura, platelet transfusion refractoriness
      and neonatal alloimmune thrombocytopenia. Biological diagnosis relies on: (1)
      detection of alloantibodies; (2) identification of the alloantigen involved in
      the immune conflict. Since the development of methods based on molecular biology,
      platelet genotyping is preferred to phenotyping. Today, most of the Platelet
      Immunology Units use PCR-RFLP or PCR-SSP, and few use real-time PCR. An
      increasing amount of commercial kits based on new technologies is now available,
      for example microarrays, fluorescent or coloured microbeads, or a combination of
      both technologies. However, an increasing number of polymorphisms have been
      discovered that are responsible for erroneous platelet genotypings. Consequently,
      it would be of interest to develop alternative technologies based on
      antigen/antibody interaction instead of DNA.

PMID- 19409831
TI  - [The role of ultrasound examination to evaluate ovarian reserve of infertile
      patients].
AB  - The accurate assessment of ovarian reserve is an essential step before the
      treatment of infertile couples. Ovarian reserve could either be evaluated through
      clinical or biological parameters, but ultrasound plays a remarkable role, since
      it permits the direct visualization and count of ovarian antral follicles.
      Nevertheless, the available literature data are conflicting about the real
      sensibility and specificity of this method to predict the exact number of
      retrieved oocytes or the occurrence of pregnancy after a procedure for medical
      assisted reproduction. New technologies have been developed, as the 3D
      ultrasound, who does not ameliorate ultrasound accuracy, but permits the
      reduction of the time necessary for patient's examination and virtually
      eliminates inter- and intra-observer bias. The place of the ovarian artery flow
      evaluation by Doppler remains unclear and need more studies.

PMID- 19409832
TI  - Morphological examination of ear: a study of an Indian population.
AB  - The uniqueness of human ear and hence its utility for identification of
      individuals has been postulated. There is however, no published data that
      establishes each individual's ear is different and distinct, and that an
      individual can be identified conclusively from comparison of the ear. Data
      presented in this study indicate that comparison of ear based on morphological
      examination can be used as a corroborative evidence.

PMID- 19409830
TI  - [Quantitative estimate of the risk of blood donation contamination by infectious
      agents].
AB  - The occurrence of asymptomatic penetration of certain infectious agents in blood
      presents a risk of transmission of one of these agents during blood transfusion.
      Although well controlled for some infectious agents (HIV, HTLV, HCV, HBV), this
      risk is nevertheless neither documented nor quantified for other pathogens that
      are responsible for serologically unscreened or undetectable infections at the
      time of blood donation. This risk is generally low in endemic situations,
      although it increases for particular time periods and locations when clustered
      cases or outbreaks occur. Prevention measures may then be implemented
      (interruption of blood collection, quarantined donations, etc.). These measures
      can have an important impact, particularly by limiting the supply of blood
      products to health care facilities. It is therefore important for these measures
      to be adapted to the risk of transmission through blood transfusion. Quantitative
      risk estimates of blood donation contamination can therefore contribute to
      guiding those measures. In this context, in early 2005, the French Public Health
      Institute (InVS) started a project with the aim of obtaining a priori
      quantitative risk estimates of contamination of a blood donation by infectious
      agents for various scenarios in terms of incidence and time-space distribution.
      The objective of this article is to update the last estimates of residual risks
      of the major transfusion-transmitted viral infections (HIV, HTLV, HCV and HBV)
      and to present the work realized by the working group << Quantitative estimate of
      the risk of blood donation contamination by infectious agents>>.

PMID- 19409833
TI  - Post-mortem tissue donation at the Institute of Legal Medicine in Hamburg:
      talking to the next of kin guidelines and first experiences.
AB  - While building up a tissue donation program at the Institute of Legal Medicine in
      Hamburg we had to organize the contact to the deceased's close relatives and to
      develop guidelines for an appropriate approach. Loosing a family member may cause
      intense psychological reactions as an Acute Stress Disorder (ICD-10F43.0). An
      "Informed Consent", according to the German Tissue Law, requires a good emotional
      contact, enough time and a detailed discussion on donation between the tissue
      coordinator and the contacted next of kin. A reliable decision for tissue
      donation can activate the coping strategies of the deceased s family.

PMID- 19409835
TI  - Survey of dental diseases in forensic autopsy cases.
AB  - Forensic odontology plays an important role in the age estimation of a corpse.
      However, some cases exhibit a large margin of error when using conventional
      morphological methods. The final purpose of this study was to survey dental
      diseases to find the factors that result in errors in age estimation. First, we
      surveyed dental status related to dental caries in forensic autopsy cases to
      examine their characteristics. We investigated 335 forensic autopsy cases with
      accurate age and gender information available from autopsy and police reports. We
      assessed the number of teeth with caries, including the number of present teeth,
      missing teeth, sound teeth, treated teeth, untreated teeth, and the total number
      of carious teeth (DMF teeth: decayed, missing, and filled teeth).Then, each mean
      number of teeth from autopsy cases was compared with that from the results of a
      control survey of dental disease performed by Akita Prefecture. The autopsy
      cases, mainly in their 50's, showed a significantly higher incidence of DMF
      teeth, missing teeth, and untreated teeth. They also showed lower incidence of
      treated teeth. The more severe carious status in the autopsy cases suggested that
      they did not regularly visit dental clinics while they were alive. We will
      continue to analyze their past physical disease histories, the causes of death,
      and their antemortem lifestyles to find the factors that lead to incorrect age
      estimation.

PMID- 19409834
TI  - Determination of aluminum in various biological materials using Instrumental
      Neutron Activation Analysis.
AB  - The determination of Aluminum (Al) in biological material by Instrumental Neutron
      Activation Analysis (INAA) contains some problems; (1) polyethylene bag enclosing
      specimen contains Al, (2) biological material includes the abundant phosphorus.
      Two elements interfere the Al determination by competing reactions, 28Si(n,p) and
      31P(n,a), and the interference factors from each elements were 3.1x10(-3) and
      1.0x10(-3), respectively. The Al concentrations in 18 biological reference
      materials and human tissues were determined by INAA.

PMID- 19409836
TI  - Phenprocoumon poisonings.
AB  - Phenprocoumon is a derivative of coumarin, used as a preventative anticoagulant
      and in the treatment of thromboembolisms. On account of its pharmacodynamic and
      pharmacokinetic properties, strict surveillance of the patient is necessary. We
      report on two cases of undocumented administration of this active pharmaceutical
      ingredient. A 57-year-old woman was discovered by her husband in an inanimate
      state. The post-mortem examination revealed many extensive haematomas. On account
      of a suspicion of third-party negligence, an autopsy was performed the same day,
      during which was established that the cause of death was a clotting abnormality,
      the cause of which remained unclear. Toxicological analyses revealed a
      concentration of phenprocoumon of 7.8 mg/l. A 76-year-old man admitted himself to
      hospital immediately upon returning from a stay abroad. In hospital, extensive
      haematomas and a massive clotting abnormality (prothrombin ratio<10%) were
      discovered. A blood sample taken the following day yielded evidence of a
      phenprocoumon concentration of 3.1 mg/l. According to his general practitioner,
      no corresponding medications had been prescribed. Suspicion of foul play in the
      introduction of this active agent resulted in a police investigation. Both cases
      demonstrate the necessity of toxicological analyses in cases of clotting
      abnormalities.

PMID- 19409837
TI  - In vivo measurement of human brain elasticity using a light aspiration device.
AB  - The brain deformation that occurs during neurosurgery is a serious issue
      impacting the patient "safety" as well as the invasiveness of the brain surgery.
      Model-driven compensation is a realistic and efficient solution to solve this
      problem. However, a vital issue is the lack of reliable and easily obtainable
      patient-specific mechanical characteristics of the brain which, according to
      clinicians' experience, can vary considerably. We designed an aspiration device
      that is able to meet the very rigorous sterilization and handling process imposed
      during surgery, and especially neurosurgery. The device, which has no electronic
      component, is simple, light and can be considered as an ancillary instrument. The
      deformation of the aspirated tissue is imaged via a mirror using an external
      camera. This paper describes the experimental setup as well as its use during a
      specific neurosurgery. The experimental data was used to calibrate a continuous
      model. We show that we were able to extract an in vivo constitutive law of the
      brain elasticity: thus for the first time, measurements are carried out per
      operatively on the patient, just before the resection of the brain parenchyma.
      This paper discloses the results of a difficult experiment and provide for the
      first time in vivo data on human brain elasticity. The results point out the
      softness as well as the highly non-linear behavior of the brain tissue.

PMID- 19409838
TI  - Practitioner influence on contact lens prescribing in the UK.
AB  - Contact lenses are mainly fitted by registered optometrists and contact lens
      opticians in the UK. Data we have gathered from annual contact lens fitting
      surveys over the past 12 years indicate that, on average, registered optometrists
      and contact lens opticians undertake 3.2 and 7.1 contact lens fits per week
      (p<0.0001). More experienced practitioners tend to fit older patients.
      Practitioners fitting more lenses per year tend to fit a higher proportion of
      soft lenses. Contact lens opticians tend to fit a higher proportion of patients
      with planned replacement and daily disposable lenses compared with optometrists.

PMID- 19409839
TI  - ATR-FT-IR spectroscopy in the region of 500-230 cm(-1) for identification of
      inorganic red pigments.
AB  - It is demonstrated that micro-ATR-FT-IR in the low wave number range (500-230 cm(
      1)) can be well used for identification of pigments in paint samples thereby
      markedly extending the possibilities of pigment identification by ATR-IR
      spectroscopy into the realm of pigments having no absorptions in the mid-IR
      region. Reference spectra of pigments can be conveniently obtained by mixing them
      with linseed oil in approximately 1:1 mass ratio. Vermilion (or cinnabar), read
      lead, different red iron oxide pigments and cadmium red can be identified. In
      some cases the method can be used alone for pigment identification and in many
      cases it provides useful additional evidence for pigment identification using
      other instrumental techniques (electron microprobe analysis, XRF, optical
      microscopy).

PMID- 19409840
TI  - Clinical performance of the 3M Rapid Detection Flu A+B Test compared to R-Mix
      culture, DFA and BinaxNOW Influenza A&B Test.
AB  - BACKGROUND: The rapid diagnosis of influenza allows for prompt patient management
      and the initiation of appropriate infection control measures to reduce spread in
      healthcare settings. OBJECTIVE: To evaluate the clinical performance of the 3M
      Rapid Detection Flu A+B Test (3MA+B) as compared to R-Mix cell culture, direct
      immunofluorescence assay (DFA) and the BinaxNOW A&B Influenza Test (BinaxNOW).
      STUDY DESIGN: Five hundred fresh respiratory samples, collected from patients
      aged 5 days to 99 years with respiratory symptoms, were tested by R-Mix culture,
      DFA, 3MA+B and BinaxNOW. Analytical sensitivity of 3MA+B was compared to BinaxNOW
      using replicates of serially diluted clinical samples positive for influenza A or
      B. RESULTS: Sensitivity, specificity, PPV and NPV for the detection of influenza
      A and B, respectively, were for R-Mix (96.9%, 100%, 100%, 99.3%; 98.1%, 100%,
      100%, 99.8%), DFA (80.4%, 99.2%, 96.1%, 95.3%; 74%, 100%, 100%, 97%), 3MA+B
      (70.1%, 99.8%, 98.6%, 93%; 86.5%, 98.7%, 88.2%, 98.4%) and BinaxNOW (46.4%, 100%,
      100%, 88.6%; 34.6%, 100%, 100%, 93%). R-Mix, DFA and 3MA+B were significantly
      (P<or=0.0001) more sensitive than BinaxNOW for the detection of both influenza A
      and B. The analytical sensitivity of 3MA+B was greater than BinaxNOW. Excessive
      blood in samples may cause 3MA+B false positive influenza B results. CONCLUSIONS:
      The 3MA+B provided superior results compared to BinaxNOW. The 3MA+B Reader
      eliminated user misinterpretation and provided quality control and result
      documentation. The improved sensitivity and easy of use makes 3MA+B an effective
      first line triage test for emergency departments, clinics and rapid response
      laboratories.

PMID- 19409841
TI  - Highly specific detection of antibodies to tick-borne encephalitis (TBE) virus in
      humans using a domain III antigen and a sensitive immune complex (IC) ELISA.
AB  - BACKGROUND: In contrast to most antibodies directed to the envelope glycoprotein
      of flaviviruses, those to the domain III (ED3) show serotype-specific reactions.
      OBJECTIVES: Only few epitopes are located on the ED3 [Oliphant T, Engle M,
      Nybakken GE, Doane C, Johnson S, Huang L, et al. Development of a humanized
      monoclonal antibody with therapeutic potential against West Nile virus. Nat Med
      2005;11:522-30; Nybakken GE, Oliphant T, Johnson S, Burke S, Diamond MS, Fremont
      DH. Structural basis of West Nile virus neutralization by a therapeutic antibody.
      Nature 2005;437:764-9; Throsby M, Geuijen C, Goudsmit J, Bakker AQ, Korimbocus J,
      Kramer RA, et al. Isolation and characterization of human monoclonal antibodies
      from individuals infected with West Nile virus. J Virol 2006;80:6982-92], and
      highly sensitive assays may be required to detect the small number of human
      antibodies to this domain. STUDY DESIGN: We have used a sensitive immune complex
      (IC) ELISA to detect antibodies to the ED3 of TBE virus [Ludolfs D, Niedrig M,
      Paweska JT, Schmitz H. Reverse ELISA for the detection of anti-West Nile virus
      IgG antibodies in humans. Eur J Clin Microbiol Infect Dis 2007;26:467-73;
      Emmerich P, Gunther S, Schmitz H. Strain-specific antibody response to Lassa
      virus in the local population of west Africa. J Clin Virol 2008;42:40-4]. This
      assay was compared with two indirect ELISAs using either the ED3 (ED3 ELISA) or
      whole tissue culture virus (TCV) (TCV ELISA) as source of antigen. Sera of 45
      patients with acute TBE infection and of 65 vaccinees were applied to determine
      the sensitivity of the IC ELISA. RESULTS: The IC ELISA detected antibodies in 107
      out of 110 samples of TBE patients and vaccinees, 106 of which were also positive
      with the TCV ELISA. Both tests had a sensitivity of >or=96%. In contrast, the ED3
      ELISA had a sensitivity of only 70%. Using samples of 98 West Africans and of 70
      Europeans without any contact to TBE virus or TBE virus antigens, the specificity
      of the IC ELISA was 100% while the specificity of the commercial TCV ELISA varied
      between 30% with samples of people with acute dengue fever or with yellow fever
      vaccination and 100% with samples of students from Hamburg without any previous
      contact to TBE. CONCLUSION: Obviously, the IC ELISA is able to detect human
      antibodies to small antigens with only few serotype-specific epitopes with high
      specificity and sensitivity.

PMID- 19409842
TI  - Energetics and biomechanics as determining factors of swimming performance:
      updating the state of the art.
AB  - The biophysical determinants related to swimming performance are one of the most
      attractive topics within swimming science. The aim of this paper was to do an
      update of the "state of art" about the interplay between performance, energetic
      and biomechanics in competitive swimming. Throughout the manuscript some recent
      highlights are described: (i) the relationship between swimmer's segmental
      kinematics (segmental velocities, stroke length, stroke frequency, stroke index
      and coordination index) and his center of mass kinematics (swimming velocity and
      speed fluctuation); (ii) the relationships between energetic (energy expenditure
      and energy cost) and swimmer's kinematics; and (iii) the prediction of swimming
      performance derived from above mentioned parameters.

PMID- 19409843
TI  - Involving health professionals in the development of an advanced symptom
      management system for young people: the ASyMS-YG study.
AB  - PURPOSE OF THE STUDY: ASyMS is an advanced symptom management system utilising
      mobile phone technology for patients to report cancer chemotherapy-related
      symptoms. The aim of this paper is to present health professionals involvement in
      the development of ASyMS for use with young people (YG) and evaluate their
      perceptions of the system. STAGE 1: Health professionals reviewed the symptoms
      chosen by young people to be included on the personal digital assistant
      questionnaire to confirm they would have universal relevance. These included:
      mouth sores, nausea, diarrhoea, vomiting and weight loss. STAGE 2: Health
      professionals completed a questionnaire prior to the study commencing, which
      suggested they felt ASyMS-YG would give young people control and facilitate
      timely interventions when symptoms occur. Post-study perceptions were sought
      through semi-structured interviews and consultation sessions with 23 health
      professionals. These showed two over-arching themes: young people's symptoms and
      perceptions of ASyMS-YG; and six sub-themes: increased control for young people;
      enhances communication between young people and health professionals; and helps
      with professional early intervention; increased support for young people; improve
      knowledge and understanding; technology appealing to young people. CONCLUSIONS:
      This early development work indicates that ASyMS-YG is acceptable to health
      professionals and their perceptions of the system were overall very positive.
      Health professionals will continue to be involved in the study through developing
      self-care guidelines and alert system, which will be tested in an exploratory
      trial (stage 3) and randomised controlled trial (stage 4) in the future.

PMID- 19409844
TI  - Breast-tissue composition and other risk factors for breast cancer in young
      women: a cross-sectional study.
AB  - BACKGROUND: Mammographic density is a heritable quantitative trait and is a
      strong risk factor for breast cancer in middle-aged and older women. However,
      little is known about the development of mammographic density in early life. We
      used MRI to measure the water content of the breast, which provides a measurement
      of the fibro-glandular content of breast tissue with similar accuracy to
      mammography, but without the attendant exposure to radiation. METHODS: Between
      December, 2003, and December, 2007, we recruited 400 young women, aged 15-30
      years, and their mothers. We used MRI scans to measure daughters' breast water
      and fat, and on the same day obtained blood for hormone assays in the follicular
      phase of the menstrual cycle for each young woman. Mothers underwent mammography
      (n=356), and a random sample (n=100) also consented to have a breast MRI scan.
      FINDINGS: In mothers, per cent water-as measured by MRI-was strongly correlated
      with per cent mammographic density (r=0.85). Per cent water in daughters (median
      44.8%) was significantly higher than in mothers (median 27.8%; p<0.0001), and was
      independently inversely associated with both their age (p=0.04) and weight
      (p<0.0001), and positively associated with their height (p<0.0001) and their
      mothers' per cent mammographic density (p<0.0001). Serum growth hormone
      concentrations, adjusted for covariates, were positively associated with per cent
      breast water (p=0.001) in a subgroup of young women (n=280) who had not used oral
      contraceptives within 6 months. INTERPRETATION: Per cent breast water was
      greatest during the ages when women are most susceptible to breast carcinogens,
      and was associated with weight, height, and mother's breast-tissue
      characteristics, and with serum concentrations of growth hormone: a breast
      mitogen that also mediates postnatal somatic growth. Mammographic density in
      middle age might partly be the result of genetic factors that affect growth and
      development in early life. FUNDING: Canadian Breast Cancer Research Alliance.

PMID- 19409846
TI  - Parasite adaptations to within-host competition.
AB  - Competition between parasite species or strains within hosts is a major
      evolutionary force in infections. In response, parasites exhibit a diverse array
      of strategies that improve their chances of growth or reproduction over
      competitors. This Review describes three types of competition that parasites face
      (exploitation, apparent and interference), identifies successful strategies for
      confronting these and discusses whether these strategies are true adaptations to
      competition. Although many studies of multiple infections have focused on disease
      outcomes (e.g. virulence), rather than on the particular parasite strategies that
      have adapted in response to the ensuing competitive interactions, these
      strategies are ultimately responsible for shaping disease outcomes of interest. A
      better understanding of parasite adaptations to competitive interactions will
      have important public health implications.

PMID- 19409845
TI  - How will genetic approaches assist in the management of respiratory diseases?
AB  - There are a number of ways in which understanding the genetic basis of either
      disease pathogenesis or treatment response might be of value in the management of
      respiratory diseases. Although some single gene defect respiratory diseases such
      as cystic fibrosis exist, the majority of common respiratory diseases are caused
      by the interaction of multiple genes and environmental factors. Newer approaches
      including the use of genome wide association studies will help define the
      underlying genetic factors. Understanding the genetic basis for disease will
      throw new light on the pathophysiology of disease, may help redefine disease
      subtypes, and may also contribute to therapeutic approaches. The aim of this
      review is to assess the current state of our knowledge of these areas of
      research.

PMID- 19409847
TI  - Comparison of four-colour IS6110-fAFLP with the classic IS6110-RFLP on the
      ability to detect recent transmission in the city of Barcelona, Spain.
AB  - The purpose of the study was to compare the IS6110-RFLP (RFLP) results obtained
      in a previous epidemiological study in the city of Barcelona, Spain [Borrell S,
      Espanol M, Orcau A, Tudo G, March F, Cayla JA, et al. Factors associated with
      differences between conventional contact tracing and molecular epidemiology in
      study of tuberculosis transmission and analysis in the city of Barcelona, Spain.
      J Clin Microbiol 2009 Jan;47(1):198-204.] with the results obtained with IS6110
      fAFLP, [Thorne N, Evans JT, Smith EG, Hawkey PM, Gharbia S, Arnold C. An IS6110
      targeting fluorescent amplified fragment length polymorphism alternative to
      IS6110-restriction fragment length polymorphism analysis for Mycobacterium
      tuberculosis DNA fingerprinting. Clin Microbiol Infect 2007 Oct;13(10):964-70.]
      on the ability to detect recent transmission. fAFLP was applied to DNA samples of
      RFLP clustered strains, with and without known epidemiological links, with the
      additional inclusion of four nucleotide-specific fluorophores to further increase
      the discrimination of the fragments obtained. Four-colour fAFLP was performed on
      123 RFLP clustered strains with no epidemiological link (NELC) and on 28
      epidemiologically linked RFLP clustered (ELC) strains grouped into 48 and 13
      clusters respectively. Clustering results obtained by the two methods were highly
      congruent in ELC strains with fAFLP allocating 92.3% of the ELCs. For the NELCs,
      RFLP results were confirmed in 39/48 (81.2%) of fAFLP-clusters with 0-1 different
      fragments and 9/48 (18.8%) differed in 2-4 fragments, which are considered
      genetically related but not recently transmitted. In conclusion, overestimation
      of recent tuberculosis transmission can occur because of the inaccurate analysis
      of RFLP results. Four-colour fAFLP allows us to differentiate between recent
      transmission strains and epidemiologically unrelated but genetically related
      strains.

PMID- 19409848
TI  - The clinical relevance of Mycobacterial pharmacogenetics.
AB  - Current anti-tuberculosis (anti-TB) drug sensitivity testing methods provide a
      dichotomous readout: isolates are reported as either drug susceptible or drug
      resistant. This report demonstrates that rapid molecular methods may provide
      information concerning both the level of resistance and cross-resistance to other
      anti-TB drugs that is important for optimal clinical management. Specific
      mutations detected by the Hain GenoType MTBDRplus test, recently approved by the
      World Health Organization (WHO) for rapid TB diagnosis and drug resistance
      testing, could inform the decision of whether to include high dose isoniazid
      (INH) when treating patients with INH mono-resistant TB, MDR-TB or XDR-TB. The
      presence of mutations in the inhA gene or promoter region generally confers low
      level INH resistance that can be overcome by high dose INH. The same mutations
      also confer resistance to ethionamide indicating little benefit from its
      inclusion in second line treatment regimens in such cases. This information has
      high clinical relevance since inhA mutations account for a large proportion of
      INH resistance, and optimized therapy regimens are crucial to improve patient
      outcomes and reduce the spread of drug resistant TB. This hypothesis needs to be
      tested in well controlled clinical and pharmacokinetic studies.

PMID- 19409849
TI  - Frequently encountered problems in transfusion medicine when managing patients
      with antibodies.

PMID- 19409850
TI  - Common and frequently encountered antibodies.

PMID- 19409851
TI  - Antibodies to high-incidence antigens.

PMID- 19409852
TI  - Drug-induced immune hemolytic anemia.

PMID- 19409853
TI  - Antibody identification.

PMID- 19409855
TI  - Corticosteroids in combination therapy for multiple sclerosis.

PMID- 19409854
TI  - NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a
      for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a
      randomised, placebo-controlled trial.
AB  - BACKGROUND: Treatment of relapsing-remitting multiple sclerosis with interferon
      beta is only partly effective, and new more effective and safe strategies are
      needed. Our aim was to assess the efficacy of oral methylprednisolone as an add
      on therapy to subcutaneous interferon beta-1a to reduce the yearly relapse rate
      in patients with relapsing-remitting multiple sclerosis. METHODS: NORMIMS (NORdic
      trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for
      treatment of relapsing-remitting Multiple Sclerosis) was a randomised, placebo
      controlled trial done in 29 neurology departments in Denmark, Norway, Sweden, and
      Finland. We enrolled outpatients with relapsing-remitting multiple sclerosis who
      had had at least one relapse within the previous 12 months despite subcutaneous
      interferon beta-1a treatment (44 microg three times per week). We randomly
      allocated patients by computer to add-on therapy of either 200 mg
      methylprednisolone or matching placebo, both given orally on 5 consecutive days
      every 4 weeks for at least 96 weeks. The primary outcome measure was mean yearly
      relapse rate. Primary analyses were by intention to treat. This trial is
      registered, number ISRCTN16202527. FINDINGS: 66 patients were assigned to
      interferon beta and oral methylprednisolone and 64 were assigned to interferon
      beta and placebo. A high proportion of patients withdrew from the study before
      week 96 (26% [17 of 66] on methylprednisolone vs 17% [11 of 64] on placebo). The
      mean yearly relapse rate was 0.22 for methylprednisolone compared with 0.59 for
      placebo (62% reduction, 95% CI 39-77%; p<0.0001). Sleep disturbance and
      neurological and psychiatric symptoms were the most frequent adverse events
      recorded in the methylprednisolone group. Bone mineral density had not changed
      after 96 weeks. INTERPRETATION: Oral methylprednisolone given in pulses every 4
      weeks as an add-on therapy to subcutaneous interferon beta-1a in patients with
      relapsing-remitting multiple sclerosis leads to a significant reduction in
      relapse rate. However, because of the small number of patients and the high
      dropout rate, these findings need to be corroborated in larger cohorts.

PMID- 19409857
TI  - Myofascial referred-pain data provide physiologic evidence of acupuncture
      meridians.
AB  - Recently published data suggest substantial anatomic, clinical, and physiologic
      (referred pain to meridian) overlap of myofascial trigger points and acupuncture
      points, particularly in the treatment of pain disorders. This qualitative study
      examines whether myofascial referred-pain data from the Trigger Point Manual can
      provide independent physiologic evidence of acupuncture meridians. Trigger point
      regions were subdivided from prior, validated trigger point region-classical
      acupuncture point correspondence results into subsets according to the 12
      acupuncture Organs of their anatomically corresponding acupuncture points
      (Bladder, Gallbladder, Heart, Kidney, Large Intestine, Liver, Lung, Pericardium,
      Small Intestine, Spleen, Stomach, and Triple Energizer). The referred-pain
      patterns for each subset of trigger point regions were graphically applied to a
      virtual human model along with the subset's corresponding acupuncture Principal
      meridian. All 12 meridian distributions were compared qualitatively with the
      summed referred-pain distributions of their anatomically corresponding trigger
      point regions. For all 12 subsets of trigger point regions, their summed referred
      pain patterns accurately predicted the distributions of their corresponding
      acupuncture meridians, particularly in the extremities. The myofascial referred
      pain data from the Trigger Point Manual provides independent physiologic evidence
      of acupuncture meridians. Understanding these meridians may enhance treatment of
      both pain and non-pain conditions. PERSPECTIVE: This article demonstrates that
      myofascial referred-pain data provide independent physiologic evidence of
      acupuncture meridians. The acupuncture tradition provides pain practitioners with
      millennia of accumulated clinical experience treating pain (and visceral)
      disorders and offers the potential for novel pain treatment approaches and
      understanding of pain neurophysiology.

PMID- 19409856
TI  - Endogenous anandamide and cannabinoid receptor-2 contribute to electroacupuncture
      analgesia in rats.
AB  - Acupuncture is widely used clinically to treat acute and chronic pain conditions,
      but the mechanisms underlying its effect are not fully understood. Although
      endocannabinoids are involved in modulation of nociception in animal models and
      in humans, their role in acupuncture analgesia has not been assessed. In this
      report, we determined the effect of electroacupuncture (EA) on the level of
      anandamide in the skin tissue and the role of cannabinoid CB1 and CB2 receptors
      in the analgesic effect of EA in an animal model of inflammatory pain.
      Inflammatory pain was induced by local injection of complete Freund's adjuvant
      (CFA) into the hind paw of rats. Thermal hyperalgesia was tested with a radiant
      heat stimulus, and mechanical allodynia was quantified with von Frey filaments.
      The anandamide concentration in the skin tissue was measured by using high
      performance liquid chromatography. EA, applied to GB30 and GB34, at 2 and 100Hz
      significantly reduced thermal hyperalgesia and mechanical allodynia induced by
      CFA injection. Compared with the sham group, EA significantly increased the
      anandamide level in the inflamed skin tissue. Local pretreatment with a specific
      CB2 receptor antagonist, AM630, significantly attenuated the antinociceptive
      effect of EA. However, the effect of EA was not significantly altered by AM251, a
      selective CB1 receptor antagonist. These findings suggest that EA potentiates the
      local release of endogenous anandamide from inflamed tissues. Activation of
      peripheral CB2 receptors contributes to the analgesic effect of EA on
      inflammatory pain. PERSPECTIVE: This study shows that electroacupuncture
      increases the anandamide level in inflammatory skin tissues, and CB2 receptors
      contribute to the analgesic effect of electroacupuncture in a rat model of
      inflammatory pain. This information improves our understanding of the mechanisms
      involved in the analgesic effect of acupuncture.

PMID- 19409858
TI  - A randomized, double-blind, placebo-controlled trial of a selective COX-2
      inhibitor, GW406381, in patients with postherpetic neuralgia.
AB  - In this randomized, double-blind, placebo-controlled study, we evaluated the
      efficacy and safety of GW406381, an investigational selective cyclooxygenase
      (COX)-2 inhibitor with both peripheral and central actions, in 209 patients with
      postherpetic neuralgia (PHN). Patients were randomly assigned to GW406381 25 mg
      or 50 mg or placebo treatments for 3 weeks. The primary efficacy outcome measure
      was the change in average daily pain intensity score from baseline to the last
      week of treatment. Both doses of GW406381 produced greater reduction in pain
      score than placebo, but the treatment difference did not reach statistical
      significance. It was possible that the 3-week duration was too short, as there
      was a tendency for increasing separation from placebo over time that did not
      appear to reach maximum effect by the end of the study for either GW406381
      treatment group. Overall, GW406381 was well tolerated in this elderly population.
      PERSPECTIVE: To our knowledge, this is the first report of a randomized,
      controlled clinical trial of a selective or nonselective COX inhibitor in
      neuropathic pain. The results of this study were inconclusive regarding the
      clinical relevance of the role of COX-2 in modulation of the symptoms of PHN.

PMID- 19409859
TI  - Do incontinence, breathing difficulties, and gastrointestinal symptoms increase
      the risk of future back pain?
AB  - Cross-sectional studies have suggested a relationship between respiratory
      disorders, incontinence, gastrointestinal symptoms, and back pain. However,
      longitudinal data are lacking. This study aimed to evaluate whether these
      disorders increase risk for the development of back pain. A total of 2943
      younger, 2298 mid-age, and 2258 older women from the Australian Longitudinal
      Study on Women's Health who reported no back pain during the preceding 12 months
      were followed for 4, 2, and 3 years, respectively. Crude and adjusted
      associations between the development of back pain and changes in the presence of
      incontinence, breathing difficulty, and gastrointestinal symptoms were assessed
      with logistic regression. Women with preexisting incontinence (prevalence ratios
      [PR]: 1.26 to 1.46) and gastrointestinal symptoms (PR: 1.24 to 1.44) and women
      who developed breathing problems (PR: 1.63 to 2.11) were more likely to develop
      back pain than women without such problems. Menstrual pain and allergy were also
      associated with back pain development. Consistent with predictions from
      physiological data, this study provides novel evidence that the presence and/or
      development of incontinence, respiratory problems, and gastrointestinal symptoms
      are associated with the development of back pain. This highlights the importance
      of comorbidities and suggests opportunities for future preventative
      interventions. PERSPECTIVE: This study demonstrates that women with incontinence,
      respiratory disorders, and gastrointestinal symptoms have increased risk for the
      development of back pain. Evidence of compromised control of the spine in people
      with incontinence and respiratory disorders and the potential for viscerosomatic
      hyperalgesia in people with gastrointestinal symptoms may provide physiological
      explanations for these findings.

PMID- 19409860
TI  - Differentiating thermal allodynia and hyperalgesia using dynamic hot and cold
      plate in rodents.
AB  - In animal studies, thermal sensitivity is mostly evaluated on the basis of
      nociceptive reaction latencies in response to a given thermal aversive stimulus.
      However, these techniques may be inappropriate to differentiate allodynia from
      hyperalgesia or to provide information differentiating the activation of
      nociceptor subtypes. The recent development of dynamic hot and cold plates,
      allowing computer-controlled ramps of temperature, may be useful for such
      measures. In this study, we characterized their interest for studying thermal
      nociception in freely moving mice and rats. We showed that escape behavior
      (jumps) was the most appropriate parameter in C57Bl/6J mice, whereas nociceptive
      response was estimated by using the sum of paw lickings and withdrawals in
      Sprague-Dawley rats. We then demonstrated that this procedure allows the
      detection of both thermal allodynia and hyperalgesia after peripheral pain
      sensitization with capsaicin in mice and in rats. In a condition of carrageenan
      induced paw inflammation, we observed the previously described thermal
      hyperalgesia, but we also revealed that rats exhibit a clear thermal allodynia to
      a cold or a hot stimulus. These results demonstrate the interest of the dynamic
      hot and cold plate to study thermal nociception, and more particularly to study
      both thermal allodynia and hyperalgesia within a single paradigm in awake and
      freely moving rodents. PERSPECTIVE: Despite its clinical relevance, thermal
      allodynia is rarely studied by researchers working on animal models. As shown
      after stimulation of capsaicin-sensitive fibers or during inflammatory pain, the
      dynamic hot and cold plate validated in the present study provides a useful tool
      to distinguish between thermal allodynia and thermal hyperalgesia in rodents.

PMID- 19409861
TI  - Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo
      controlled trial.
AB  - The efficacy and tolerability of oral lacosamide (200, 400, and 600 mg/day) was
      evaluated in patients with painful diabetic neuropathy in a double-blind,
      randomized, placebo-controlled trial. The primary target dose to be confirmed was
      lacosamide 400 mg/day. Efficacy was assessed by changes in pain scale scores from
      baseline, with changes over the last 4 weeks of the 12-week maintenance period
      regarded as the primary endpoint. Endpoint reductions in mean pain score were
      higher with all doses of lacosamide, reaching the level of significance with 400
      mg/day (P = .05). Over the treatment period (titration + maintenance), pain
      relief was significantly higher than placebo with lacosamide 400 (P = .02) and
      600 mg/day (P = .03). Lacosamide had an early-onset effect with significant
      reductions over placebo during the titration period. Nonparametric and mixed
      model analysis approaches gave similar results, supporting significant efficacy
      at 400 mg/day. Secondary criteria such as Patient's Global Impression of Change,
      responder rates, and pain-free days provided additional support. Adverse events
      included dizziness, nausea, and headache. Incidence of cognitive and behavioral
      adverse events was low. This trial suggests that lacosamide has beneficial
      effects and may be a suitable treatment option for patients with diabetic
      neuropathic pain. PERSPECTIVE: This study presents efficacy and safety results of
      a phase 3, double-blind, placebo-controlled trial of the anticonvulsant drug
      lacosamide in patients with painful diabetic neuropathy. Lacosamide treatment at
      a dose of 400 mg/day reduced diabetic neuropathic pain with a favorable safety
      and tolerability profile that may be suitable for patients with diabetes.

PMID- 19409863
TI  - Palladium nanoparticles modified electrode for the selective detection of
      catecholamine neurotransmitters in presence of ascorbic acid.
AB  - Palladium (Pd) nanoparticles are directly fabricated on glassy carbon electrode
      (GCE) and indium tin oxide electrode (ITO) by simple electrochemical deposition
      process. The Pd nanoparticles modified ITO electrode surface has been studied in
      detail using scanning electron microscopy (SEM) and atomic force microscopy
      (AFM). The electrodeposited nano Pd particles are found as spherical shaped in
      the size range of 39-78 nm. The X-ray diffraction (XRD) analysis reveals that the
      electrodeposited nano Pd film possesses the face centered cubic crystalline
      structure. This nano Pd film modified GCE effectively exhibits the electro
      oxidation signals for the detection of catecholamines epinephrine (EP),
      norepinephrine (NEP) and dopamine (DA). Especially, the proposed nano Pd film
      modified GCE successfully showed two well separated anodic oxidation peaks for
      the detection of catecholamines and ascorbic (AA) in mixture solution. The
      proposed nano Pd film modified electrode also retains the advantage of easy
      fabrication, high sensitivity and good repeatability. Finally, this type of nano
      Pd film modified electrode supports the selective detection of catecholamines in
      injection solutions.

PMID- 19409862
TI  - Dose-dependent effects of icilin on thermal preference in the hindpaw and face of
      rats.
AB  - Icilin induces wet dog shakes (WDS) in rodents when injected systemically and
      activates the cold receptor TRPM8 and putative cold receptor TRPA1. It is assumed
      that WDS reflect an enhanced cold sensitivity; however, none have examined the
      relationship between WDS and cutaneous cold sensitivity following systemic
      icilin. In this study, we sought to characterize the effect of systemic and
      central icilin administration on WDS and thermal preference with either hindpaw
      or facial stimulation. It was found that a low dose of icilin (.025 mg), which
      transiently elevated WDS, decreased preference for cold with hindpaw stimulation
      (15 and 45 degrees C) when administered ip or it. Intracisternal administration
      of this dose produced similar results for facial stimulation (10 and 48 degrees
      C), but had no effect when administered ip. In contrast a high dose of icilin
      (.25 mg), which persistently elevated WDS, strongly increased preference for cold
      with hindpaw stimulation and had no effect on thermal preference with facial
      stimulation. These findings indicate that at the low concentration, systemic and
      central icilin enhances cold sensitivity, likely via TRPM8 and TRPA1 activation.
      In contrast, systemic icilin at the high concentration produces peripheral and/or
      central effects that diminish cold sensitivity, while WDS is maintained at a
      persistent rate. PERSPECTIVE: Icilin is a unique compound that produces
      dissociable effects on an innate behavior (WDS) and on operant behaviors related
      to thermal perception. This compound could help clarify the relationship between
      peripheral cold transduction and the central induction of thermogenesis and
      nocifensive behaviors, as well as alterations that produce pathological pain.

PMID- 19409864
TI  - Determination of p-phenylenediamine and its metabolites MAPPD and DAPPD in
      biological samples using HPLC-DAD and amperometric detection.
AB  - A sensitive and selective HPLC method using a diode array detector (DAD) and an
      electrochemical detector (ECD) in series has been developed and validated for the
      quantitative measurement of p-phenylenediamine and its acetylated metabolites N
      acetyl-p-phenylenediamine (MAPPD) and N,N'-diacetyl-p-phenylenediamine (DAPPD) in
      biological samples. The separation was carried out on a hydrophilic modified AQUA
      C(18) column and the mobile phase was composed of acetonitrile: ammonium acetate
      solution (5:95, 25 mM, v/v). Spectrophotometric detection was performed at 240 or
      255 nm and amperometric detection was carried out using a positive oxidation
      potential of 400 mV. The quantification of the three analytes was validated in
      the range of 0.05-50 microM and the established limits of determination were 0.5
      microM for PPD and MAPPD and 1 microM for DAPPD. The standard deviations (N=9)
      were lower than 7.5% at a concentration of 1 microM. The samples were stabilised
      with ascorbic acid to prevent PPD from oxidizing. Pretreatment of samples or
      analyte enrichment before sample injection is not required. The method proved to
      be accurate, sensitive and sufficiently specific. It was applied to the
      ecotoxicological study of the kinetics of the PPD N-acetylation in cell lysates
      in two different media.

PMID- 19409865
TI  - Detection of landiolol using high-performance liquid chromatography/fluorescence:
      a blood esterase-sensitive ultra-short-acting beta(1)-receptor antagonist.
AB  - Landiolol hydrochloride, a new adrenergic beta(1)-selective antagonist having an
      ultra-short half-life, is used to prevent tachyarrhythmia during surgery. Since
      landiolol is thought to be rapidly hydrolyzed to an inactivate metabolite by
      esterases, quantification of the drug concentration in the blood is impractical.
      The landiolol concentration in blood was halved within 5 min after blood
      sampling. This degradation was effectively prevented by pre-treatment with
      neostigmine (100 microg) in the sampling tube, but not by EDTA pre-treatment,
      indicating that landiolol could be metabolized by pseudocholinesterase in plasma.
      After the one-step solid-phase extraction, fluorescence detection of landiolol
      reduced chromatographic background signals and then improved assay sensitivity to
      the lower limit of 10 ng/ml in blood; this reproducible approach yielded
      coefficient variation of less than 6%. The blood concentration-time profile of
      landiolol hydrochloride in patients of the present investigation afforded more
      practical assessment than previously reported studies, thus improving accuracy
      and facilitating detailed pharmacokinetic study in relation to the
      pharmacological action of drug.

PMID- 19409866
TI  - Predicting interest in cosmetic surgery: interactive effects of appearance-based
      rejection sensitivity and negative appearance comments.
AB  - This study investigated effects of appearance-based rejection sensitivity
      (Appearance-RS) - the dispositional tendency to anxiously expect rejection based
      on one's appearance - in a sample of 133 American college students. Participants
      were randomly assigned to write an essay about either a negative or positive
      appearance comment they had received in the past. Compared to participants with
      lower Appearance-RS, those with higher Appearance-RS felt more rejected and
      expressed greater interest in cosmetic surgery after recalling a negative versus
      positive appearance comment. Content analysis of the essays revealed that
      negative appearance comments were most often made in reference to one's body
      weight/shape/size; positive appearance comments were most often made in reference
      to one's overall appearance. Peers/friends/romantic partners were the most
      frequently cited source of both positive and negative appearance comments.
      Overall, this research suggests that the interaction between the person and the
      situation is important to consider when predicting cosmetic surgery interest.

PMID- 19409867
TI  - The lived experience of alopecia areata: a qualitative study.
AB  - This study explored experiences of individuals living with alopecia areata (AA)
      and alopecia universalis (AU) and investigated their accounts of adjusting to,
      and coping with, such conditions. Whilst previous research has primarily focused
      on the adverse psychosocial impact of alopecia, this investigation used
      Interpretive Phenomenological Analysis to provide a more holistic perspective.
      Biographical interviews were undertaken with 12 participants (7 women; 5 men)
      diagnosed with alopecia for periods ranging between 2 and 49 years. Results
      revealed that strategies used by participants evolved over time and that there
      were clear gender differences. In the early stages, participants did not want to
      contemplate that their hair loss would be lasting and managed the condition via
      concealment. Later coping strategies reflected an embodied acceptance with
      participants managing the effects of AA/AU and becoming more optimistic about
      living with the condition. Limitations of the study are discussed as well as
      implications for patient care.

PMID- 19409868
TI  - Evaluation of the particle release of porous PMMA cements during curing.
AB  - Poly(methyl methacrylate) (PMMA) remains the most common bone substitute material
      used for vertebroplasty. A possible downside with this material is that the
      Young's modulus of the cement is significantly higher than that of osteoporotic
      vertebral cancellous bone. In consequence, an increased fracture risk has been
      demonstrated for the adjacent vertebral bodies after reinforcement. A solution
      could be to prepare porous bone cements with a lower bulk modulus as suggested by
      De Wijn (De Wijn JR. Poly(methyl methacrylate)-aqueous phase blends: in situ
      curing porous materials. J Biomed Mater Res 1976;10:625-35). The potential of
      such porous PMMA cements for application in vertebroplasty has been shown in the
      literature. The present study was performed to study the release of particles,
      e.g. powder particles such as barium sulfate or hydroxyapatite, from PMMA cements
      containing an aqueous phase. The aqueous phase was introduced to act as a pore
      forming phase to soften the cement and is thought to be released when applied in
      vivo. Cement particle release is not suitable for the application as they may
      cause adverse reactions such as embolism. The purpose of the present study was to
      investigate the amount of the particles released in relation to various aqueous
      solutions and different preparation methods. As a result of the work presented
      here, a method was found to reduce the particle release by delayed admixing of
      the aqueous phase to the partially polymerized PMMA/MMA mixture. This method
      leads to a reduction in particle release of more than 50%, e.g. reduced from 1.3
      to 0.6g particles per 4ml of cement. Despite these improvements, particle release
      could not be reduced to a suitable level comparable to regular vertebroplasty
      cement. Therefore, the practicability of the initially promising invention of
      porous PMMA, in order to make regular PMMA cement more compliant with cancellous
      bone remains an unsolved issue.

PMID- 19409870
TI  - The effect of surface treatment on the surface texture and contact angle of
      electrochemically deposited hydroxyapatite coating and on its interaction with
      bone-forming cells.
AB  - This work demonstrates the effects of both surface preparation and surface post
      treatment by exposure to electron beam on the surface texture, contact angle and
      the interaction with bone-forming cells of electrochemically deposited
      hydroxyapatite (HAp) coating. Both the surface texture and the contact angle of
      the ground titanium substrate changed as a result of either heat treatment
      following soaking in NaOH solution or soaking in H(2)O(2) solution. Consequently,
      the shape of the current transients during potentiostatic deposition of HAp
      changed, and the resulting coatings exhibited different surface textures and
      contact angles. The developed interfacial area ratio Sdr and the core fluid
      retention index Sci were found more reliable than the mean roughness R(a) and the
      root-mean-square roughness Z(rms) in correlating the adhesion of the coating to
      the metal substrate and the cellular response with surface texture. The NaOH
      pretreatment provided the highest surface area and induced the highest cell
      attachment, even though the H(2)O(2) treatment provided the highest
      hydrophilicity to the metal substrate. Electrodeposition at pH 6 was found
      preferable compared to electrodeposition at pH 4.2. The ability to modify the
      cellular response by exposure to unique electron-beam surface treatment was
      demonstrated. The very high hydrophilicity of the as-deposited HAp coating
      enhanced its bioactivity.

PMID- 19409869
TI  - Relationship between scaffold channel diameter and number of regenerating axons
      in the transected rat spinal cord.
AB  - Regeneration of endogenous axons through a Schwann cell (SC)-seeded scaffold
      implant has been demonstrated in the transected rat spinal cord. The formation of
      a cellular lining in the scaffold channel may limit the degree of axonal
      regeneration. Spinal cords of adult rats were transected and implanted with the
      SC-loaded polylactic co-glycollic acid (PLGA) scaffold implants containing seven
      parallel-aligned channels, either 450mum (n=19) or 660microm in diameter (n=14).
      Animals were sacrificed after 1, 2 and 3months. Immunohistochemistry for
      neurofilament expression was performed. The cross-sectional area of fibrous
      tissue and regenerative core was calculated. We found that the 450microm
      scaffolds had significantly greater axon fibers per channel at the 1month (186+/
      37) and 3month (78+/-11) endpoints than the 660microm scaffolds (90+/-19 and 40+/
      6, respectively) (p=0.0164 and 0.0149, respectively). The difference in the area
      of fibrous rim between the 450 and 660microm channels was most pronounced at the
      1month endpoint, at 28,046+/-6551 and 58,633+/-7063microm(2), respectively
      (p=0.0105). Our study suggests that fabricating scaffolds with smaller diameter
      channels promotes greater regeneration over larger diameter channels. Axonal
      regeneration was reduced in the larger channels due to the generation of a large
      fibrous rim. Optimization of this scaffold environment establishes a platform for
      future studies of the effects of cell types, trophic factors or pharmacological
      agents on the regenerative capacity of the injured spinal cord.

PMID- 19409871
TI  - The effect of hyaluronic acid on brushite cement cohesion.
AB  - The improvement of calcium phosphate cement (CPC) cohesion is essential for its
      application in highly blood perfused regions. This study reports the
      effectiveness of hyaluronic acids of different molecular weights in the
      enhancement of brushite cement cohesion. The cement was prepared using a powder
      phase composed of a mixture of beta-tricalcium phosphate and monocalcium
      phosphate monohydrate, whereas the liquid phase was formed by 0.5M citric acid
      solution modified by the addition of hyaluronic acid of different molecular
      weights. It was found that medium and high molecular weight hyaluronic acid
      enhances the cement cohesion and scarcely affects the cement mechanical
      properties. However, concentrations >0.5% (w/v) were less efficient to prevent
      the cement disintegration. It is concluded that hyaluronic acid could be applied
      efficiently to reduce brushite cement disintegration.

PMID- 19409872
TI  - SCCT guidelines for performance of coronary computed tomographic angiography: a
      report of the Society of Cardiovascular Computed Tomography Guidelines Committee.

PMID- 19409873
TI  - Mitochondrial kinases and their molecular interaction with cardiolipin.
AB  - Mitochondrial isoforms of creatine kinase (MtCK) and nucleoside diphosphate
      kinase (NDPK-D) are not phylogenetically related but share functionally important
      properties. They both use mitochondrially generated ATP with the ultimate goal of
      maintaining proper nucleotide pools, are located in the intermembrane/cristae
      space, have symmetrical oligomeric structures, and show high affinity binding to
      anionic phospholipids, in particular cardiolipin. The structural basis and
      functional consequences of the cardiolipin interaction have been studied and are
      discussed in detail in this review. They mainly result in a functional
      interaction of MtCK and NDPK-D with inner membrane adenylate translocator,
      probably by forming proteolipid complexes. These interactions allow for
      privileged exchange of metabolites (channeling) that ultimately regulate
      mitochondrial respiration. Further functions of the MtCK/membrane interaction
      include formation of cardiolipin membrane patches, stabilization of mitochondria
      and a role in apoptotic signaling, as well as in case of both kinases, a role in
      facilitating lipid transfer between two membranes. Finally, disturbed cardiolipin
      interactions of MtCK, NDPK-D and other proteins like cytochrome c and truncated
      Bid are discussed more generally in the context of apoptosis and necrosis.

PMID- 19409875
TI  - RhoA leads to up-regulation and relocalization of utrophin in muscle fibers.
AB  - Up-regulation of utrophin, a homolog of dystrophin, is known to ameliorate the
      dystrophic phenotype in animal models of Duchenne muscular dystrophy. We have
      previously demonstrated that the active form of RhoA (RhoAV14) increases the
      expression of utrophin and its localization at the plasma membrane in cultured
      myoblasts. In this paper, we ask whether RhoAV14 can up-regulate utrophin also in
      mice. A plasmid encoding for RhoAV14 was injected into skeletal muscles followed
      by electroporation. Muscles expressing RhoAV14 were analyzed by Western
      immunoblotting, real time PCR amplification and immunohistochemistry. We found
      that RhoAV14 increased utrophin protein expression and distribution specifically
      at the plasma membrane in muscle fibers without any effect on utrophin
      transcription. Utrophin up-regulation, uncoupled from that of its mRNA, has been
      previously observed in pathological processes and in normal regenerating
      conditions.

PMID- 19409874
TI  - The angiotensin II-AT1 receptor stimulates reactive oxygen species within the
      cell nucleus.
AB  - We and others have reported significant expression of the Ang II Type 1 receptor
      (AT1R) on renal nuclei; thus, the present study assessed the functional pathways
      and distribution of the intracellular AT1R on isolated nuclei. Ang II (1nM)
      stimulated DCF fluorescence, an intranuclear indicator of reactive oxygen species
      (ROS), while the AT1R antagonist losartan or the NADPH oxidase (NOX) inhibitor
      DPI abolished the increase in ROS. Dual labeling of nuclei with antibodies
      against nucleoporin 62 (Nup62) and AT1R or the NADPH oxidase isoform NOX4
      revealed complete overlap of the Nup62 and AT1R (99%) by flow cytometry, while
      NOX4 was present on 65% of nuclei. Treatment of nuclei with a PKC agonist
      increased ROS while the PKC inhibitor GF109203X or PI3 kinase inhibitor LY294002
      abolished Ang II stimulation of ROS. We conclude that the Ang II-AT1R-PKC axis
      may directly influence nuclear function within the kidney through a redox
      sensitive pathway.

PMID- 19409876
TI  - ADP-ribosylation factor like 7 (ARL7) interacts with alpha-tubulin and modulates
      intracellular vesicular transport.
AB  - ADP-ribosylation factor (ARF) like 7 (ARL7, also named ARL4C) is a member of ARL
      family and recent studies showed that it is involved in the AI-dependent
      cholesterol secretion process. Yet its biological function remains largely
      unknown. Using a MALDI-TOF/MS analysis, we identified alpha-tubulin interacted
      with ARL7. The interaction was confirmed by GST pull-down assay and co
      immunoprecipitation in renal carcinoma cell 786-O in which we found the
      endogenous ARL7 is expressed. This is the second ARL member found interacting
      with tubulin after ARL8. In addition, ARL7Q72L, a GTP-binding form, promoted the
      transferrin transport from early endosome to recycling endosome significantly.
      The above data suggested that ARL7 might modulate the intracellular vesicular
      transport via interaction with microtubules.

PMID- 19409877
TI  - A novel sorting strategy of trichosanthin for hijacking human immunodeficiency
      virus type 1.
AB  - Trichosanthin (TCS) is a type I ribosome-inactivating protein that plays dual
      role of plant toxin and anti-viral peptide. The sorting mechanism of such an
      exogenous protein is in long pursuit. Here, we examined TCS trafficking in cells
      expressing the HIV-1 scaffold protein Gag, and we found that TCS preferentially
      targets the Gag budding sites at plasma membrane or late endosomes depending on
      cell types. Lipid raft membrane but not the Gag protein mediates the association
      of TCS with viral components. After Gag budding, TCS is then released in
      association with the virus-like particles to generate TCS-enriched virions. The
      resulting TCS-enriched HIV-1 exhibits severely impaired infectivity. Overall, the
      observations indicate the existence of a unique and elaborate sorting strategy
      for hijacking HIV-1.

PMID- 19409878
TI  - Exon junction complex enhances translation of spliced mRNAs at multiple steps.
AB  - Translation of spliced mRNAs is enhanced by exon junction complex (EJC), which is
      deposited on mRNAs as a result of splicing. Although this phenomenon itself is
      well known, the underlying molecular mechanism remains poorly understood. Here we
      show, using siRNAs against Y14 and eIF4AIII and spliced or intronless constructs
      that contain different types of internal ribosome entry sites (IRESes), that Y14
      and eIF4AIII increase translation of spliced mRNAs before and after formation of
      the 80S ribosome complex, respectively. These results suggest that EJC modulates
      translation of spliced mRNA at multiple steps.

PMID- 19409879
TI  - Trans-splicing as a novel method to rapidly produce antibody fusion proteins.
AB  - To cultivate the use of trans-splicing as a novel means to rapidly express
      various antibody fusion proteins, we tried to express antibody-reporter enzyme
      fusions in a COS-1 co-transfection model. When a vector designed to induce trans
      splicing with IgH pre-mRNA was co-transfected with a vector encoding the mouse
      IgM locus, the expression of V(H)-secreted human placental alkaline phosphatase
      (SEAP) as well as Fab-SEAP were successfully expressed both in mRNA and protein
      levels. Especially, the vectors encoding complementary sequence to Smu as a
      binding domain was accurate and efficient, producing trans-spliced mRNA of up to
      2% of cis-spliced one. Since Smu sequence should exist in every IgH pre-mRNA, our
      finding will lead to the rapid production and analysis of various antibody-enzyme
      fusions suitable for enzyme-linked immunosorbent assay (ELISA) or antibody
      dependent enzyme prodrug therapy (ADEPT).

PMID- 19409880
TI  - Leptin enhances CC-chemokine ligand expression in cultured murine macrophage.
AB  - Despite accumulating evidence, the role of leptin in chemokine expression is
      poorly understood. In this study, we evaluated the effects of leptin on CC
      chemokine ligands (CCLs), CCL3, CCL4, and CCL5 gene expression in cultured murine
      macrophage, J774A.1 cells. Expression of all these CCLs mRNA was gradually
      increased and significant up-regulation was observed for 3-12 h exposure to
      leptin (1 microM). The phosphorylated signal transducer and activator of
      transcription 3 (pSTAT3) was significantly increased for 5-20 min exposure to
      leptin, and it was localized in leptin receptor-positive macrophage. Pretreatment
      with AG490 (100 microM), a janus kinase 2 (JAK2) inhibitor, significantly
      suppressed leptin-induced pSTAT3 increases and the up-regulation of CCLs mRNA
      expression. In conclusion, leptin enhances CCLs expression in cultured murine
      macrophage, through activation of a JAK2-STAT3 pathway. Therefore, a new paradigm
      of leptin-mediated chemokine expression may lead to the clarification of complex
      immune systems in future.

PMID- 19409881
TI  - Epidermal growth factor increases claudin-4 expression mediated by Sp1 elevation
      in MDCK cells.
AB  - Epidermal growth factor (EGF) increases claudin-4 expression in Madin-Darby
      canine kidney (MDCK) cells. Here we examined what regulatory mechanisms are
      involved in the EGF-induced claudin-4 elevation. EGF transiently increased
      claudin-4 mRNA at 3h and persistently increased its protein for 24h without
      affecting claudin-1 expression. EGF increased p-ERK1/2 levels, which were
      inhibited by U0126, a MEK inhibitor. The exogenous expression of constitutively
      activated MEK increased claudin-4 expression. These results indicate that the
      activation of ERK1/2 is involved in the EGF-induced claudin-4 elevation. EGF
      increased Sp1 expression within 1h, which was inhibited by U0126. In
      immunocytochemistry, Sp1 was distributed in nucleus in control and the EGF
      treated cells. The EGF-induced claudin-4 elevation was inhibited by mithramycin,
      a Sp1 inhibitor, and Sp1 small interfering RNA. We suggest that EGF activates a
      MEK/ERK pathway and increases Sp1 expression, resulting in an elevation of
      claudin-4 expression.

PMID- 19409882
TI  - Mucopolysaccharidosis IIIB: oxidative damage and cytotoxic cell involvement in
      the neuronal pathogenesis.
AB  - Sanfilippo B syndrome (Mucopolysaccharidosis IIIB, MPS IIIB) is a lysosomal
      storage disease due to mutations in the gene encoding alpha-N
      acetylglucosaminidase and is characterized by a severe neurological disorder.
      Although several studies have been reported for the murine model of the disease,
      the molecular basis and the sequence of events leading to neurodegeneration
      remain to be clarified. We previously suggested the possible involvement of the
      reactive oxygen species in the disease pathogenesis. In the present paper we
      extended the analysis of oxidative stress by evaluating the production of
      superoxide ions throughout the CNS and by evaluating the effect of the stress on
      the cellular macromolecules. These approaches applied to one-month-old, three
      month-old and six-month-old mice revealed that oxidative stress is present in the
      affected cerebrum and cerebellum tissues from one month from birth, and that it
      results primarily in protein oxidation, both in the cerebrum and cerebellum, with
      lipid peroxidation, and especially DNA oxidation, appearing milder and restricted
      essentially to the cerebellum. We also identified additional genes possibly
      associated with the neuropathology of MPS IIIB disease. Real time RT-PCR analysis
      revealed an altered expression of the Sod1, Ret, Bmp4, Tgfb, Gzmb and Prf1 genes.
      Since Gzmb and Prf1 are proteins secreted by NK/cytotoxic T-cells, these data
      suggest the involvement of cytotoxic cells in the neuronal pathogenesis.
      Extending our previous study, findings reported in the present paper show that
      oxidative stress and all the analyzed stress-related pathological changes occur
      very early in the disease course, most likely before one month of age.

PMID- 19409883
TI  - The transcriptional repressor RP58 is crucial for cell-division patterning and
      neuronal survival in the developing cortex.
AB  - The neocortex and the hippocampus comprise several specific layers containing
      distinct neurons that originate from progenitors at specific development times,
      under the control of an adequate cell-division patterning mechanism. Although
      many molecules are known to regulate this cell-division patterning process, its
      details are not well understood. Here, we show that, in the developing cerebral
      cortex, the RP58 transcription repressor protein was expressed both in
      postmitotic glutamatergic projection neurons and in their progenitor cells, but
      not in GABAergic interneurons. Targeted deletion of the RP58 gene led to
      dysplasia of the neocortex and of the hippocampus, reduction of the number of
      mature cortical neurons, and defects of laminar organization, which reflect
      abnormal neuronal migration within the cortical plate. We demonstrate an
      impairment of the cell-division patterning during the late embryonic stage and an
      enhancement of apoptosis of the postmitotic neurons in the RP58-deficient cortex.
      These results suggest that RP58 controls cell division of progenitor cells and
      regulates the survival of postmitotic cortical neurons.

PMID- 19409884
TI  - The transcription factor Six1a plays an essential role in the craniofacial
      myogenesis of zebrafish.
AB  - Transcription factor Six1a plays important roles in morphogenesis, organogenesis,
      and cell differentiation. However, the role of Six1a during zebrafish cranial
      muscle development is still unclear. Here, we demonstrated that Six1a was
      required for sternohyoideus, medial rectus, inferior rectus, and all pharyngeal
      arch muscle development. Although Six1a was also necessary for myod and myogenin
      expression in head muscles, it did not affect myf5 expression in cranial muscles
      that originate from head mesoderm. Overexpression of myod enabled embryos to
      rescue all the defects in cranial muscles induced by injection of six1a
      morpholino (MO), suggesting that myod is directly downstream of six1a in
      controlling craniofacial myogenesis. However, overexpression of six1a was unable
      to rescue arch muscle defects in the tbx1- and myf5-morphants, suggesting that
      six1a is only involved in myogenic maintenance, not its initiation, during arch
      muscle myogenesis. Although the craniofacial muscle defects caused by pax3-MO
      phenocopied those induced by six1a-MO, injection of six1a, myod or myf5 mRNA did
      not rescue the cranial muscle defects in pax3 morphants, suggesting that six1a
      and pax3 do not function in the same regulatory network. Therefore, we proposed
      four putative regulatory pathways to understand how six1a distinctly interacts
      with either myf5 or myod during zebrafish craniofacial muscle development.

PMID- 19409885
TI  - BMP type II receptor regulates positioning of outflow tract and remodeling of
      atrioventricular cushion during cardiogenesis.
AB  - Signaling of bone morphogenetic protein (BMP) via type I and type II receptors is
      involved in multiple processes contributing to cardiogenesis. To investigate the
      role of the BMP type II receptor (BMPRII) in heart development, the BMPRII gene
      was deleted throughout the embryo during gastrulation using a Mox2-Cre transgene.
      BMPRII(flox/-);Mox2-Cre mice exhibited cardiac defects including double-outlet
      right ventricle, ventricular septal defect (VSD), atrioventricular (AV) cushion
      defects, and thickened valve leaflets. To characterize the tissue-specific
      functions of BMPRII in cardiogenesis, a series of Cre transgenes (alphaMHC-, Tie2
      , Wnt1-, and SM22alpha-Cre) was employed. Interestingly, myocardial development
      was normal when the BMPRII gene was deleted in myocardial cells using Mox2-Cre,
      alphaMHC-Cre, or SM22alpha-Cre transgenes, suggesting that signaling by other BMP
      type II receptors may compensate for the absence of BMPRII in the myocardial
      cells. AV cushion defects including atrial septal defect, membranous VSD, and
      thickened valve leaflets were found in BMPRII(flox/-);Tie2-Cre mice. Abnormal
      positioning of the aorta was observed in BMPRII(flox/-);Wnt1-Cre and BMPRII(flox/
      );SM22alpha-Cre mice. Taken together, these results demonstrate that endocardial
      BMPRII expression is required for septal formation and valvulogenesis. Moreover,
      mesenchymal BMPRII expression in the outflow tract cushion is required for proper
      positioning of the aorta.

PMID- 19409886
TI  - Cell-cell interactions during remodeling of the intestine at metamorphosis in
      Xenopus laevis.
AB  - Amphibian metamorphosis is accompanied by extensive intestinal remodeling. This
      process, mediated by thyroid hormone (TH) and its nuclear receptors, affects
      every cell type. Gut remodeling in Xenopus laevis involves epithelial and
      mesenchymal proliferation, smooth muscle thickening, neuronal aggregation,
      formation of intestinal folds, and shortening of its length by 75%. Transgenic
      tadpoles expressing a dominant negative TH receptor (TRDN) controlled by
      epithelial-, fibroblast-, and muscle-specific gene promoters were studied. TRDN
      expression in the epithelium caused abnormal development of virtually all cell
      types, with froglet guts displaying reduced intestinal folds, thin muscle and
      mesenchyme, absence of neurons, and reduced cell proliferation. TRDN expression
      in fibroblasts caused abnormal epithelia and mesenchyme development, and
      expression in muscle produced fewer enteric neurons and a reduced inter-muscular
      space. Gut shortening was inhibited only when TRDN was expressed in fibroblasts.
      Gut remodeling results from both cell-autonomous and cell-cell interactions.

PMID- 19409887
TI  - Axial patterning in snakes and caecilians: evidence for an alternative
      interpretation of the Hox code.
AB  - It is generally assumed that the characteristic deregionalized body plan of
      species with a snake-like morphology evolved through a corresponding
      homogenization of Hox gene expression domains along the primary axis. Here, we
      examine the expression of Hox genes in snake embryos and show that a collinear
      pattern of Hox expression is retained within the paraxial mesoderm of the trunk.
      Genes expressed at the anterior and most posterior, regionalized, parts of the
      skeleton correspond to the expected anatomical boundaries. Unexpectedly however,
      also the dorsal (thoracic), homogenous rib-bearing region of trunk, is
      regionalized by unconventional gradual anterior limits of Hox expression that are
      not obviously reflected in the skeletal anatomy. In the lateral plate mesoderm we
      also detect regionalized Hox expression yet the forelimb marker Tbx5 is not
      restricted to a rudimentary forelimb domain but is expressed throughout the
      entire flank region. Analysis of several Hox genes in a caecilian amphibian,
      which convergently evolved a deregionalized body plan, reveals a similar global
      collinear pattern of Hox expression. The differential expression of posterior,
      vertebra-modifying or even rib-suppressing Hox genes within the dorsal region is
      inconsistent with the homogeneity in vertebral identity. Our results suggest that
      the evolution of a deregionalized, snake-like body involved not only alterations
      in Hox gene cis-regulation but also a different downstream interpretation of the
      Hox code.

PMID- 19409888
TI  - Suppression of T cell activation by hirsutenone, isolated from the bark of Alnus
      japonica, and its therapeutic advantages for atopic dermatitis.
AB  - The increasing prevalence and severity of atopic dermatitis during recent decades
      has prompted the development of safe and more highly effective drugs. Although
      topical corticosteroids have been used for more than 50 years as first line
      therapy for atopic dermatitis, their potential side effects limits their clinical
      uses. In light of this, steroid-free topical calcineurin inhibitors were
      developed and have been used in patients with moderate to severe atopic
      dermatitis. In the present study, we examined if hirsutenone suppressed the
      profiles of atopic dermatitis development in vitro via mimicry of calcineurin
      inhibitor actions in mouse splenocytes and RBL-2H3 mast cells. Our results showed
      that hirsutenone effectively inhibited T cell activation by blocking
      dephosphorylation of nuclear factor of activated T cells (NFAT). This inhibition
      was confirmed by inactivation of mitogen-activated protein kinases (MAPKs), which
      subsequently inhibited production of cytokine mRNAs (interleukin-2, -4, -5, -13
      and interferon-gamma) after T cell receptor stimulation. We also showed that the
      early T cell activation marker, CD25, was suppressed in the presence of
      hirsutenone after T cell receptor stimulation with anti-CD3. Moreover,
      degranulation of mast cells was remarkably suppressed, comparable to that by
      cyclosporine A. This indicates that hirsutenone may specifically inhibit calcium
      activated processes in both T cells and mast cells. Therefore, our results
      suggest that hirsutenone may be a new topical drug candidate, which probably acts
      by mimicking calcineurin inhibitor mechanisms.

PMID- 19409889
TI  - The gastric ulcer-healing action of allylpyrocatechol is mediated by modulation
      of arginase metabolism and shift of cytokine balance.
AB  - The role of the ariginine-metabolism in the healing action of the Piper betle
      phenol, allylpyrocatechol (APC) and omeprazole against indomethacin-induced
      stomach ulceration in mouse was investigated. Indomethacin (18 mg/kg) was found
      to induce maximum stomach ulceration in Swiss albino mice on the 3rd day of its
      administration, which was associated with reduced arginase activity (21.6%,
      P<0.05), endothelial nitric oxide synthase (eNOS) expression (72%, P<0.001), and
      IL-4 and TGF-beta levels, along with increased inducible nitric oxide synthase
      (iNOS) (9.3 folds, P<0.001) expression, nitrite (2.29 folds, P<0.001), IL-1beta
      and IL-6 generation. Besides providing comparable healing as omeprazole (3 mg/kg
      x 3 days), APC (5 mg/kg x 3 days) shifted the iNOS/NO axis to the
      arginase/polyamine axis as revealed from the increased arginase activity (73.1%,
      P<0.001), eNOS expression (67.8%, P<0.001), and reduced iNOS expression (65.6%,
      P<0.001) and nitrite level (53.2%, P<0.001). These can be attributed to a
      favourable anti-/pro-inflammatory cytokines ratio, generated by APC. The healing
      by omeprazole was however, not significantly associated with those parameters.

PMID- 19409890
TI  - Emodin augments calcium activated chloride channel in colonic smooth muscle cells
      by Gi/Go protein.
AB  - Emodin is a natural anthraquinone in rhubarb. It has been identified as a
      prokinetic drug for gastrointestinal motility in Chinese traditional medicine.
      Emodin contracts smooth muscle by increasing the concentration of intracellular
      Ca(2+). In many smooth muscles, increasing intracellular Ca(2+) activates Ca(2+)
      activated Cl(-) channels (ClCA). The study was aimed to investigate the effects
      of emodin on ClCA channels in colonic smooth muscle. 4 channel physiology signal
      acquire system was used to measure isometric contraction of smooth muscle strips.
      ClCA currents were recorded by EPC10 with perforated whole cell model. Emodin
      contracted strips and cells in colonic smooth muscle and augmented ClCA currents.
      Niflumic acid (NFA) and 4', 4'-diisothiostilbene-2, 2-disulfonic acid (DIDS)
      blocked the effects. Gi/Go protein inhibits protein kinase A (PKA) and protein
      kinase C (PKC), and PKA and PKC reduced ClCA currents. Pertussis toxin (PTX, a
      special inhibitor of Gi/Go protein), 8-bromoadenosine 38, 58-cyclic monophosphate
      (8-BrcAMP, a membrane-permeant protein kinase A activator) and Phorbol-12
      myristate-13-acetate (PMA, a membrane-permeant protein kinase C activator)
      inhibited the effects on ClCA currents significantly. Our findings suggest that
      emodin augments ClCA channels to contract smooth muscle in colon, and the effect
      is induced mostly by enhancement of membrane Gi/Go protein signal transducer
      pathway.

PMID- 19409891
TI  - Metabolic profiling identifies lung tumor responsiveness to erlotinib.
AB  - A subtype of non-small cell lung cancer, bronchioalveolar adenocarcinoma (BAC),
      is more prevalent in Asian female non-smokers, and is more likely to respond to
      treatment with tyrosine kinase inhibitors such as erlotinib and gefitinib.
      Nuclear magnetic resonance and mass spectrometry-based metabolomic analysis of
      extracts from two different lung lesions and surrounding non-cancerous tissues of
      a BAC patient showed novel protein and phospholipid-associated metabolic
      differences that correlated with tumor development as well as PET and erlotinib
      sensitivity.

PMID- 19409892
TI  - Neuropilin2 expressed in gastric cancer endothelial cells increases the
      proliferation and migration of endothelial cells in response to VEGF.
AB  - The structure and characteristics of the tumor vasculature are known to be
      different from those of normal vessels. Neuropilin2 (Nrp2), which is expressed in
      non-endothelial cell types, such as neuronal or cancer cells, functions as a
      receptor for both semaphorin and vascular endothelial growth factor (VEGF). After
      isolating tumor and normal endothelial cells from advanced gastric cancer tissue
      and normal gastric mucosa tissues, respectively, we identified genes that were
      differentially expressed in gastric tumor endothelial (TEC) and normal
      endothelial cells (NEC) using DNA oligomer chips. Using reverse transcriptase
      PCR, we confirmed the chip results by showing that Nrp2 gene expression is
      significantly up-regulated in TEC. Genes that were found to be up-regulated in
      TEC were also observed to be up-regulated in human umbilical vein endothelial
      cells (HUVECs) that were co-cultured with gastric cancer cells. In addition,
      HUVECs co-cultured with gastric cancer cells showed an increased reactivity to
      VEGF-induced proliferation and migration. Moreover, overexpression of Nrp2 in
      HUVECs significantly enhanced the proliferation and migration induced by VEGF.
      Observation of an immunohistochemical analysis of various human tumor tissue
      arrays revealed that Nrp2 is highly expressed in the tumor vessel lining and to a
      lesser extent in normal tissue microvessels. From these results, we suggest that
      Nrp2 may function to increase the response to VEGF, which is more significant in
      TEC than in NEC given the differential expression, leading to gastric TEC with
      aggressive angiogenesis phenotypes.

PMID- 19409893
TI  - Cytokeratins 8 and 18 in adult human corneal endothelium.
AB  - The aim of this study was to determine if cytokeratins (CKs) 8 and 18--typical
      epithelial cell markers--are constitutively expressed in adult human corneal
      endothelium. Cryosections, paraffin-embedded sections and corneal endothelial
      imprints obtained from eleven adult human corneal discs not suitable for
      transplantation were used. Different fixative solutions were applied before
      indirect immunofluorescent or enzymatic staining was performed with antibodies
      against CK8 (Chemicon), CK18 (Dako and Sigma) and CK8/18 (Novocastra). Semi
      quantitative RT-PCR and Western blotting (mRNA or proteins were isolated from
      Millicell membranes) were used to determine cytokeratin mRNA and protein levels.
      Approximately 50% of the corneal endothelial cells were positive for CK8
      (Chemicon), CK18 (Sigma) and the CK pair 8/18 (Novocastra) in the endothelium
      when acetone was used for fixation. Four and 52% CK18-positive cells were
      observed using immunofluorescent and enzymatic immunohistochemistry,
      respectively, when the CK18 antibody from Dako was used. No signal was detected
      when 4% formalin or 10% paraformaldehyde was used as a fixative, irrespective of
      the antibody used. CK8 and CK18 proteins and mRNAs were detected in the
      endothelium of all tested corneas by Western blotting or semi-quantitative RT
      PCR, respectively. We detected both CK8 and CK18 in the endothelium of all
      specimens at both the protein and mRNA levels. These results clearly demonstrate
      that cells of the corneal endothelium express CKs 8 and 18 and share some
      features with simple epithelia.

PMID- 19409894
TI  - Both compensation and recovery of skilled reaching following small
      photothrombotic stroke to motor cortex in the rat.
AB  - Large lesions produced by stroke to the forelimb region of motor cortex of the
      rat feature post-stroke improvement that in the main is due to compensation. The
      present study describes both recovery and compensation of forelimb use in a reach
      to-eat (skilled reaching) task following small photothrombotic stroke. The rats
      were pretrained before stroke, and then assessed using endpoint measures and
      biometric movement analysis during rehabilitation in the acute and chronic post
      stroke periods. Histological and MRI analysis indicated that the stroke consisted
      of a small lesion surrounded by cortex featuring scattered cell loss, likely of
      the large pyramidal cells that characterize the forelimb region of motor cortex.
      The stroke reduced reaching success, especially on the most demanding measure of
      success on first reach attempts, in the acute period, but with rehabilitation,
      performance returned to pre-stroke levels. Reach movements as assessed by
      biometric measures were severely impaired acutely but displayed significant
      recovery chronically although this recovery was not complete. The results suggest
      that not only do rats show post-stroke compensation in skilled reaching but they
      can also display functional recovery. It is suggested that recovery is mediated
      by the spared neurons in the peri-infarct region of forelimb motor cortex. The
      results demonstrate the utility of a small lesion model for studying post-stroke
      neural and behavioral change and support the view that optimal post-stroke
      treatment should be directed toward limiting tissue loss.

PMID- 19409895
TI  - Pallidal stimulation that improves parkinsonian motor symptoms also modulates
      neuronal firing patterns in primary motor cortex in the MPTP-treated monkey.
AB  - Deep brain stimulation (DBS), a surgical therapy for advanced Parkinson's disease
      (PD), is known to change neuronal activity patterns in the pallidothalamic
      circuit. Whether these effects translate to the motor cortex and, if so, how they
      might modulate the functional responses of individual neurons in primary motor
      cortex remains uncertain. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      treated monkey was implanted with a DBS lead spanning internal and external
      segments of globus pallidus. During therapeutic stimulation (135 Hz) for rigidity
      and bradykinesia, neurons in primary motor cortex (M1) exhibited an inhibitory
      phase-locking (2-5 ms) to the stimulus, an overall decrease in mean discharge
      rate, and an increase in response specificity to passive limb movement. Sub
      therapeutic DBS (30 Hz) still produced entrainment to the stimulation, but the
      mean discharge rate and specificity to movement were not changed. Lower
      stimulation intensities (at 135 Hz), which no longer improved motor symptoms, had
      little effect on M1 activity. These findings suggest that DBS improves
      parkinsonian motor symptoms by inducing global changes in firing pattern and rate
      along the pallido-thalamocortical sensorimotor circuit.

PMID- 19409897
TI  - Protective effects of microglia in multiple sclerosis.
AB  - The role of microglia in demyelinating neurodegenerative diseases such as
      multiple sclerosis (MS) and its animal model experimental autoimmune
      encephalomyelitis (EAE) is still controversial. Although microglial cells are
      known as the professional phagocytes and executer of innate immunity in the
      central nervous system (CNS), it is believed that microglia are rather neurotoxic
      in these diseases. However, there is recent evidence indicating that microglia
      could also exert a neuroprotective function in MS and EAE. First evidence for the
      protective effect of immune cells in CNS diseases emerged from studies in
      invertebrates. In the medicinal leech, the process of regeneration begins with
      rapid activation and accumulation of phagocytic glial cells at the lesion site
      followed by phagocytosis of damaged tissue by these cells which promoted robust
      neural regeneration. In vertebrates, several lines of evidence demonstrate that
      microglia are also involved in neuroprotection by the secretion of soluble
      mediators that trigger neural repair and usually contribute to the creation of an
      environment conductive for regeneration. The efficient removal of apoptotic cells
      and clearance of debris at the lesion site and the recruitment of stem cell
      populations as well as the induction of neurogenesis are directly correlated.
      These findings suggest that microglia play a major role in creating a
      microenvironment for repair and regenerative processes in demyelinating
      neuroinflammatory diseases.

PMID- 19409898
TI  - Prospective study of the long-term effects of bariatric surgery on liver injury
      in patients without advanced disease.
AB  - BACKGROUND & AIMS: Severe obesity is implicated in development of nonalcoholic
      fatty liver disease (NAFLD). Bariatric surgery induces weight loss and increases
      survival time of obese patients, but little is known about its effects on liver
      damage. We performed a 5-year prospective study to evaluate fibrosis and
      nonalcoholic steatosis (NASH) in severely obese patients after bariatric surgery.
      METHODS: Bariatric surgery was performed on 381 patients. Clinical and biological
      data, along with liver biopsies, were collected before and at 1 and 5 years after
      surgery. RESULTS: Five years after surgery, levels of fibrosis increased
      significantly, but 95.7% of patients maintained a fibrosis score <or= F1. The
      percentage of patients with steatosis decreased from 37.4% before surgery to 16%,
      the NAFLD score from 1.97 to 1, ballooning from 0.2 to 0.1. Inflammation remained
      unchanged. The percentage of patients with probable or definite NASH decreased
      significantly over 5 years, from 27.4% to 14.2%. The kinetics of insulin
      resistance (IR) paralleled that of steatosis and ballooning; the greatest
      improvements occurred within the first year and were sustained 5 years later.
      Steatosis and ballooning occurred more frequently in patients with a refractory
      IR profile. In multivariate analysis, the refractory IR profile independently
      predicted the persistence of steatosis and ballooning 5 years later. CONCLUSIONS:
      Five years after bariatric surgery for severe obesity, almost all patients had
      low levels of NAFLD, whereas fibrosis slightly increased. Steatosis and
      ballooning were closely linked to IR; long-term effects could be predicted by
      early improvement in IR.

PMID- 19409896
TI  - Delayed gastric emptying and enteric nervous system dysfunction in the rotenone
      model of Parkinson's disease.
AB  - Gastrointestinal (GI) dysfunction is the most common non-motor symptom of
      Parkinson's disease (PD). Symptoms of GI dysmotility in PD include early satiety
      and weight loss from delayed gastric emptying and constipation from impaired
      colonic transit. Understanding the pathophysiology and treatment of these
      symptoms in PD patients has been hampered by the lack of investigation into GI
      symptoms and pathology in PD animal models. We report that the parkinsonian
      neurotoxin and mitochondrial complex I inhibitor rotenone causes delayed gastric
      emptying and enteric neuronal dysfunction when administered chronically to rats
      in the absence of major motor dysfunction or CNS pathology. When examined 22-28
      days after initiation of rotenone infusion by osmotic minipump (3 mg/kg/day), 45%
      of rotenone-treated rats had a profound delay in gastric emptying.
      Electrophysiological recording of neurally-mediated muscle contraction in
      isolated colon from rotenone-treated animals confirmed an enteric inhibitory
      defect associated with rotenone treatment. Rotenone also induced a transient
      decrease in stool frequency that was associated with weight loss and decreased
      food and water intake. Pathologically, no alterations in enteric neuron numbers
      or morphology were apparent in rotenone-treated animals. These results suggest
      that enteric inhibitory neurons may be particularly vulnerable to the effects of
      mitochondrial inhibition by parkinsonian neurotoxins and provide evidence that
      parkinsonian gastrointestinal abnormalities can be modeled in rodents.

PMID- 19409899
TI  - Placental steroidogenesis in rats is independent of signaling pathways induced by
      retinoic acids.
AB  - We investigated the effects of retinoic acids (RAs) on steroid hormone production
      and mRNA expression of steroidogenic enzymes in rat placenta in vitro and in
      vivo. In the rat trophoblast giant cell line Rcho-1, the natural retinoid X
      receptor (RXR) agonist 9-cis retinoic acid (9cRA) and synthetic RXR agonist
      LG100268 slightly promoted production of progesterone and androgen, whereas the
      natural retinoic acid receptor (RAR) agonist all-trans retinoic acid (atRA) and
      synthetic RAR agonist TTNPB did not. Furthermore, although administration of atRA
      and 9cRA into the rat uterus at 13.5days postcoitum robustly induced mRNA
      expression of cellular retinol binding protein II, the gene for which is targeted
      by RAR and/or RXR, in the placenta, neither RA affected the expression of
      placental steroidogenic enzymes, and both had little effect on progesterone and
      androgen levels in the placenta and embryo, suggesting that placental
      steroidogenesis is not regulated by RAs in rats.

PMID- 19409900
TI  - Current knowledge on the melatonin system in teleost fish.
AB  - Melatonin is a much conserved feature in vertebrates that plays a central role in
      the entrainment of daily and annual physiological rhythms. Investigations aiming
      at understanding how melatonin mediates the effects of photoperiod on crucial
      functions and behaviors have been very active in the last decades, particularly
      in mammals. In fish a clear-cut picture is still missing. Here we review the
      available data on (i) the sites of melatonin production in fish, (ii) the
      mechanisms that control its daily and annual rhythms of production and (iii) the
      characterization of its different receptor subtypes, their location and
      regulation. The in vivo and in vitro data on melatonin effects on crucial
      neuroendocrine regulations, including reproduction, growth, feeding and
      behavioral responses, are also reviewed. Finally we discuss how manipulation of
      the photic cues impact on fish circannual clock and annual cycle of reproduction,
      and how this can be used for aquaculture purposes.

PMID- 19409901
TI  - Could parasites destabilize mouse populations? The potential role of
      Pterygodermatites peromysci in the population dynamics of free-living mice,
      Peromyscus leucopus.
AB  - Peromyscus leucopus populations exhibit unstable population dynamics.
      Mathematical models predict instability with chronic parasite infections that
      reduce host fecundity when the parasite distribution within the host population
      is close to random. We examined the role the nematode Pterygodermatites peromysci
      may play in influencing the dynamics of these mice. There were seven
      gastrointestinal worms infecting mice. Pterygodermatites peromysci was the most
      prevalent and varied seasonally from 12.3% in November to 36.0% in July.
      Prevalence was higher in adults (30.8%) than juveniles (4.6%) and there were no
      statistical differences in prevalence or intensity between the sexes. Overall the
      distribution was random; the relationship between log variance and log mean of P.
      peromysci intensity from 17 sites was not significantly different from unity.
      There were significant relationships between infection and breeding condition,
      suggesting parasites could be the cause of reduced female breeding. A generalized
      linear model found the likelihood of P. peromysci infection in adults increased
      with body mass, the presence of other helminths, and when hosts were in breeding
      condition. Likewise, the intensity of infection was positively related to co
      infections and body mass. Pterygodermatites peromysci infection was associated
      with the presence of the oxyurid nematode Syphacia peromysci but co-infection was
      lower in females than males. Amongst females, co-infection was greater when
      breeding, particularly during lactation. The P. peromysci age-intensity
      relationship increased with age and rose to an asymptote as expected for a
      parasite with constant mortality and no acquired immunity. Overall, P. peromysci
      had a random distribution and was associated with reduced breeding; we discuss
      how these destabilizing processes may influence the dynamics of P. leucopus.

PMID- 19409902
TI  - Daggerblade grass shrimp (Palaemonetes pugio): A reservoir host for yellow-head
      virus (YHV).
AB  - Yellow-head virus (YHV) is a major pathogen in penaeid shrimps. We surveyed 13
      crustacean species in eight families from two orders that are commonly found in
      the Mississippi coastal area and freshwater environments as potential reservoir
      or carrier hosts of YHV. Using semi-nested polymerase chain reaction (PCR) on
      relatively small sample sizes, we did not detect any natural infection. However,
      when the daggerblade grass shrimp, Palaemonetes pugio, and the blue crab,
      Callinectes sapidus, were exposed to YHV by injection and per os, YHV was
      detected in the tissue of P. pugio and in the hemolymph of C. sapidus when tested
      by semi-nested reverse transcription PCR (RT-PCR) and real time quantitative
      reverse transcription PCR (qRT-PCR). YHV replicated in P. pugio, causing 8%
      mortality (9/112) after injection, with the viral titer reaching a peak at 14days
      post-inoculation (dpi) and remaining detectable at 36dpi. The number of infected
      animals and viral load, however, were relatively low but the virus still remained
      infectious to penaeids when administered by feeding. When YHV was injected into
      P. pugio, in situ hybridization detected a positive response to it at 7dpi in
      connective tissue of hepatopancreas, muscle, and midgut. Viral RNA in injected C.
      sapidus remained at a low level for 3days, and it was not detected from 7dpi
      onwards. In fed C. sapidus, the viral RNA reached a peak at 3dpi and still
      detectable at 7dpi, but it became undetectable at 14 and 21dpi. These data
      suggest that P. pugio under some conditions could act as a reservoir host for YHV
      but that the blue crab could serve as a poor, short term carrier host only.

PMID- 19409904
TI  - Different behaviors in vivo of mutations in the beta hairpin loop of the DNA
      polymerases of the closely related phages T4 and RB69.
AB  - The T4 and RB69 DNA replicative polymerases are members of the B family and are
      highly similar. Both replicate DNA with high fidelity and employ the same
      mechanism that allows efficient switching of the primer terminus between the
      polymerase and exonuclease sites. Both polymerases have a beta hairpin loop
      (hereafter called the beta loop) in their exonuclease domains that plays an
      important role in active-site switching. The beta loop is involved in strand
      separation and is needed to stabilize partially strand-separated exonuclease
      complexes. In T4 DNA polymerase, modification of the beta-loop residue G255 to
      Ser confers a strong mutator phenotype in vivo due to a reduced ability to form
      editing complexes. Here, we describe the RB69 DNA polymerase mutant with the
      equivalent residue (G258) changed to Ser but showing only mild mutator activity
      in vivo. On the other hand, deletion of the tip of the RB69 beta loop confers a
      strong mutator phenotype in vivo. Based on detailed mutational spectral analyses,
      DNA binding activities, and coupled polymerase/exonuclease assays, we define the
      differences between the T4 and RB69 polymerases. We propose that their beta loops
      facilitate strand separation in both polymerases, while the residues that form
      the loop have low structural constraints.

PMID- 19409905
TI  - N-acetyl-L-glutamate kinase (NAGK) from oxygenic phototrophs: P(II) signal
      transduction across domains of life reveals novel insights in NAGK control.
AB  - N-Acetyl-L-glutamate kinase (NAGK) catalyzes the first committed step in arginine
      biosynthesis in organisms that perform the cyclic pathway of ornithine synthesis.
      In eukaryotic and bacterial oxygenic phototrophs, the activity of NAGK is
      controlled by the P(II) signal transduction protein. Recent X-ray analysis of
      NAGK-P(II) complexes from a higher plant (Arabidopsis thaliana) and a
      cyanobacterium (Synechococcus elongatus) revealed that despite several
      differences, the overall structure of the complex is highly similar. The present
      study analyzes the functional conservation of P(II)-mediated NAGK regulation in
      plants and cyanobacteria to distinguish between universal properties and those
      that are specific for the different phylogenetic lineages. This study shows that
      plant and cyanobacterial P(II) proteins can mutually regulate the NAGK enzymes
      across the domains of life, implying a high selective pressure to conserve P(II)
      NAGK interaction over more than 1.2 billion years of separate evolution. The non
      conserved C-terminus of S. elongatus NAGK was identified as an element, which
      strongly enhances arginine inhibition and is responsible for most of the
      differences between S. elongatus and A. thaliana NAGK with respect to arginine
      sensitivity. Both P(II) proteins relieve arginine inhibition of NAGK, and in both
      lineages, P(II)-mediated relief from arginine inhibition is antagonized by 2
      oxoglutarate. Together, these properties highlight the conserved role of P(II) as
      a signal integrator of the C/N balance sensed as 2-oxoglutarate to regulate
      arginine synthesis in oxygenic phototrophs.

PMID- 19409906
TI  - Light and nutrient availability affect the size-scaling of growth in
      phytoplankton.
AB  - Communities of marine phytoplankton consist of cells of many different sizes. The
      size-structure of these communities often varies predictably with environmental
      conditions in aquatic systems. It has been hypothesized that physiological
      differences in nutrient and light requirements and acquisition efficiencies
      contribute to commonly observed correlations between phytoplankton community size
      structure and resource availability. Using physiological models we assess how
      light and nutrient availability can alter the relative growth rates of
      phytoplankton species of different cell sizes. Our models predict a change in the
      size dependence of growth rate depending on the severity of limitation by light
      and nutrient availability. Under conditions of growth-saturated resource supply,
      phytoplankton growth rate (mol C cell(-1)time(-1)) scales with cell volume with a
      size-scaling exponent of 3/4; light limitation reduces the size-scaling exponent
      to approximately 2/3, and nutrient limitation decreases the exponent to 1/3 as a
      consequence of the size-scaling of resource acquisition. Exponents intermediate
      between 1/3 and 3/4 occur under intermediate availability of light and nutrients
      and depend on the size-scaling of pigment photoacclimation and the size range
      examined.

PMID- 19409903
TI  - TRAF2 suppresses basal IKK activity in resting cells and TNFalpha can activate
      IKK in TRAF2 and TRAF5 double knockout cells.
AB  - Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) and TRAF5 are
      adapter proteins involved in TNFalpha-induced activation of the c-Jun N-terminal
      kinase and nuclear factor kappaB (NF-kappaB) pathways. Currently, TNFalpha
      induced NF-kappaB activation is believed to be impaired in TRAF2 and TRAF5 double
      knockout (T2/5 DKO) cells. Here, we report instead that T2/5 DKO cells exhibit
      high basal IkappaB kinase (IKK) activity and elevated expression of NF-kappaB
      dependent genes in unstimulated conditions. Although TNFalpha-induced receptor
      interacting protein 1 ubiquitination is indeed impaired in T2/5 DKO cells,
      TNFalpha stimulation further increases IKK activity in these cells, resulting in
      significantly elevated expression of NF-kappaB target genes to a level higher
      than that in wild-type cells. Inhibition of NIK in T2/5 DKO cells attenuates
      basal IKK activity and restores robust TNFalpha-induced IKK activation to a level
      comparable with that seen in wild-type cells. This suggests that TNFalpha can
      activate IKK in the absence of TRAF2 and TRAF5 expression and receptor
      interacting protein 1 ubiquitination. In addition, both the basal and TNFalpha
      induced expression of anti-apoptotic proteins are normal in T2/5 DKO cells, yet
      these DKO cells remain sensitive to TNFalpha-induced cell death, due to the
      impaired recruitment of anti-apoptotic proteins to the TNFR1 complex in the
      absence of TRAF2. Thus, our data demonstrate that TRAF2 negatively regulates
      basal IKK activity in resting cells and inhibits TNFalpha-induced cell death by
      recruiting anti-apoptotic proteins to the TNFR1 complex rather than by activating
      the NF-kappaB pathway.

PMID- 19409907
TI  - Stochastic modelling of prey depletion processes.
AB  - The modelling of prey-predator interactions is of major importance for the
      understanding of population dynamics. Classically, these interactions are
      modelled using ordinary differential equations, but this approach has the
      drawbacks of assuming continuous population variables and of being deterministic.
      We propose a general approach to stochastic modelling based on the concept of
      functional response for a prey depletion process with a constant number of
      predators. Our model could involve any kind of functional response, and permits a
      likelihood-based approach to statistical modelling and stable computation using
      matrix exponentials. To illustrate the method we use the Holling-Juliano
      functional response and compare the outcomes of our model with a deterministic
      counterpart considered by Schenk and Bacher [2002. Functional response of a
      generalist insect predator to one of its prey species in the field. Journal of
      Animal Ecology 71 (3), 524-531], who observed the depletion of Cassida rubiginosa
      due to its exclusive predator, Polistes dominulus. The predation was found to be
      Holling type III, reflecting the ability of the predator to regulate its prey.
      Our approach corroborates this result, but suggests that the prey depletion
      census should have been performed more often, and that predation features were
      significantly different between the two years for which data are available.

PMID- 19409908
TI  - Independent contrasts and regression through the origin.
AB  - Following the pioneering work of Felsenstein and Garland, phylogeneticists have
      been using regression through the origin to analyze comparative data using
      independent contrasts. The reason why regression through the origin must be used
      with such data was revisited. The demonstration led to the formulation of a
      permutation test for the coefficient of determination and the regression
      coefficient estimates in regression through the origin. Simulations were carried
      out to measure type I error and power of the parametric and permutation tests
      under two models of data generation: regression models I and II (correlation
      model). Although regression through the origin assumes model I data, in
      independent contrast data error is present in the explanatory as well as the
      response variables. Two forms of permutations were investigated to test the
      regression coefficients: permutation of the values of the response variable y,
      and permutation of the residuals of the regression model. The simulations showed
      that the parametric tests or any of the permutation tests can be used when the
      error is normal, which is the usual assumption in independent contrast studies;
      only the test by permutation of y should be used when the error is highly
      asymmetric; and the parametric tests should be used when extreme values are
      present in covariables. Two examples are presented. The first one concerns non
      specificity in fish parasites of the genus Lamellodiscus, the second the richness
      in parasites in 78 species of mammals.

PMID- 19409909
TI  - Dual lattice model of the evolution of facultative symbiosis with continuous
      Prisoner's Dilemma game.
AB  - Mutualism is ubiquitous in nature and is thought to have played a key role in the
      history of life. However, how mutualism could evolve despite being prone to
      unilateral exploitation is a puzzling question in evolutionary ecology. Some
      theoretical studies have shown that spatial structure of habitat can facilitate
      the emergence and maintenance of mutualism. However, they are based on the simple
      assumption that the trait in question is discrete: each individual is either a
      mutualist or a non-mutualist. In this article I develop a simple simulation model
      of coevolution of facultative symbiosis using a one-shot continuous Prisoner's
      Dilemma game to investigate the evolutionary dynamics of mutualism between two
      species. In this model I assume continuous traits for both species from -1 (fully
      deceptive) to 1 (fully cooperative). The habitat has a dual-lattice structure,
      each layer is inhabited by one species. Interspecific interaction is restricted
      between two corresponding sites of the two layers. Without limitation on the
      magnitude of a single mutation, I find that mutualism can arise and persist when
      the intrinsic reproduction rate is low (but is above a threshold) and the
      benefit/cost ratio of the cooperative strategy is large, which is consistent with
      Yamamura et al. [2004. Evolution of mutualism through spatial effects. J. Theor.
      Biol. 226, 421-428]. In these cases, extreme antagonism often evolves starting
      from a neutral population that seems nearly stable, but once mutualism arises,
      the cooperative individuals quickly increase and both the populations eventually
      become mutualistic on average, although they are polymorphic. However, when the
      effect of a single mutation was limited to be small, extreme antagonism is much
      likely to dominate unless the intrinsic reproduction rate is low. When only one
      species is allowed to evolve, mutualism arises when the initial strategy of the
      other species is cooperative. Otherwise, excessive deception evolves in the
      former, and the latter often becomes driven to extinction.

PMID- 19409910
TI  - 3',4'-Dihydroxyflavonol prevents diabetes-induced endothelial dysfunction in rat
      aorta.
AB  - AIMS: Diabetes increases oxidant stress and impairs endothelium-dependent
      relaxation. We investigated whether the antioxidant 3',4'-dihydroxyflavonol
      (DiOHF) reduces the release of superoxide (O(2)(-)) and preserves endothelial
      function in aortae from diabetic rats. MAIN METHODS: Type-1 diabetes was induced
      in Sprague-Dawley rats by streptozotocin (STZ) treatment (55 mg/kg i.v.) and
      vascular reactivity and superoxide generation were assessed in aortic rings using
      standard organ bath techniques and lucigenin-enhanced chemiluminescence
      respectively. KEY FINDINGS: Eight weeks after STZ treatment blood glucose was
      elevated (39.4+/-0.4 mM) compared to citrate treated control rats (5.5+/-0.1 mM,
      P<0.05) and there was an increased aortic generation of O(2)(-) (control 670+/
      101, diabetic 1535+/-249 units/mg dry weight, P<0.05). In aortic rings
      acetylcholine (ACh)-induced relaxation was impaired (R(max) control 78+/-2,
      diabetic 66+/-3%, P<0.01) whereas endothelium-independent relaxation to sodium
      nitroprusside (SNP) was unaffected (R(max) control 100+/-1, diabetic 101+/-2%).
      When aortic rings were acutely exposed to DiOHF (10(-5) M) there was a
      significant reduction in the detection of O(2)(-) (control 124+/-15, diabetic
      165+/-21 units/mg, P<0.01) and enhanced relaxation to ACh (R(max) control 84+/-3,
      diabetic 87+/-3%). Two separate groups of rats (control and diabetic) were
      treated daily with DiOHF (5 mg/kg i.p.) for 7 days. DiOHF treatment reduced
      superoxide generation in diabetic aortae (untreated diabetic 1471+/-358, DiOHF
      treated diabetic 580+/-115 units/mg, P<0.05) and enhanced acetylcholine-induced
      relaxation (R(max) untreated diabetic 58+/-5, DiOHF-treated diabetic 71+/-4%,
      P<0.05). SIGNIFICANCE: DiOHF, acutely in vitro or after 1 week treatment in vivo,
      reduces oxidant stress and preserves endothelium-dependent relaxation in aortae
      from diabetic rats.

PMID- 19409911
TI  - Miogadial and miogatrial with alpha,beta-unsaturated 1,4-dialdehyde moieties-
      novel and potent TRPA1 agonists.
AB  - AIMS: Most of the terpenoids with an alpha,beta-unsaturated 1,4-dialdehyde
      moiety, which are found in plants, fungi, and insects, have a pungent taste.
      However, the neural receptors responsible for the pungency of these terpenoids
      have not been identified yet. The transient receptor potential ankyrin 1 (TRPA1)
      and transient receptor potential vanilloid 1 (TRPV1), which are expressed in the
      nociceptive neurons, induce a sensation of heat on activation by some pungent
      ingredients in food. In this study, we selected miogadial (MD), miogatrial (MT),
      and polygodial (PG) from the terpenoids with an alpha,beta-unsaturated 1,4
      dialdehyde moiety and examined the effects of these 3 terpenoids on TRPA1 or
      TRPV1. MAIN METHODS: TRPV1 and TRPA1 activity by 3 terpenoids were evaluated
      using Ca(2+) imaging and patch-clamp methods in mammalian cells that express TRP
      heterologously and mouse sensory neurons. KEY FINDINGS: The 3 terpenoids
      activated TRPA1 that was heterologously expressed in HEK293 or CHO cells. The
      potencies of activation by the 3 terpenoids were equal and almost 10 times
      stronger than that of allyl isothiocyanate (AITC), which is known as the most
      potent TRPA1 agonist among all natural products. Moreover, these 3 terpenoids
      exhibited increased intracellular Ca(2+) concentration in mouse sensory neuron
      cells compared to AITC. High concentrations of the 3 terpenoids also activated
      TRPV1 that was heterologously expressed in HEK293 cells. SIGNIFICANCE: These
      results indicated that MD, MT, and PG were more potent in activating TRPA1 than
      TRPV1, and suggested that they primarily activate TRPA1 to induce pungency.

PMID- 19409912
TI  - Inhibition of suicidal erythrocyte death by resveratrol.
AB  - AIMS: Pleiotropic effects of resveratrol include antioxidant activity and
      inhibition of cyclooxygenase with decrease of PGE(2) formation. In erythrocytes
      oxidation and PGE(2) activate Ca(2+)-permeable cation channels. The Ca(2+)-entry
      leads to activation of Ca(2+)-sensitive K(+) channels with subsequent cell
      shrinkage and cell membrane scrambling with phosphatidylserine exposure at the
      erythrocyte surface. Cell shrinkage and phosphatidylserine exposure are hallmarks
      of suicidal erythrocyte death or eryptosis. Eryptotic cells adhere to the
      vascular wall thus compromising microcirculation and are cleared from circulating
      blood thus leading to anemia. The present experiments explored whether
      resveratrol influences eryptosis. MAIN METHODS: Erythrocyte phosphatidylserine
      exposure was identified by annexin V-binding, cell volume estimated from forward
      scatter and cytosolic Ca(2+) activity determined utilizing Fluo3 fluorescence in
      FACS analysis. KEY FINDINGS: Energy depletion (48 h glucose removal)
      significantly increased Fluo3 fluorescence and annexin V-binding and decreased
      forward scatter, effects significantly blunted by resveratrol (>/=5 microM).
      Moreover, oxidative stress (30 min 0.3 mM tert-butylhydroperoxide) and isoosmotic
      cell shrinkage (48 h replacement of extracellular chloride by gluconate)
      similarly triggered eryptosis, effects again significantly blunted in the
      presence of resveratrol. SIGNIFICANCE: Resveratrol is a potent inhibitor of
      suicidal erythrocyte death during energy depletion, oxidative stress and
      isoosmotic cell shrinkage. The nutrient could thus counteract anemia and
      impairment of microcirculation under conditions with excessive eryptosis.

PMID- 19409913
TI  - Proteasome inhibition prevents experimentally-induced endothelial dysfunction.
AB  - AIMS: We recently demonstrated that non-toxic inhibition of the proteasome
      upregulates antioxidative enzymes and leads to an adaptive transcriptional
      pattern in endothelial cells. We therefore hypothesized that proteasome
      inhibition could prevent experimentally-induced endothelial dysfunction. As there
      are conflicting data about the effects of proteasome inhibition on endothelial
      function, we investigated whether proteasome inhibition could prevent
      experimentally-induced endothelial dysfunction. MAIN METHODS: Endothelial
      dysfunction in isolated rat aortic rings was induced by incubation of rings with
      TNFalpha for 48 h. To study the effects of the inhibition of the proteasome,
      selected rings were co-treated with proteasome inhibitors. Vasorelaxation and
      expression of genes involved in endothelial function were evaluated. KEY
      FINDINGS: Incubation of rat aortic rings with TNFalpha for 48 h led to
      significant dose-dependent reduction of acetylcholine-induced vasorelaxation. Co
      incubation with TNFalpha and the proteasome inhibitor MG132 resulted in dose
      dependent improvement of endothelium-dependent vasorelaxation in comparison to
      rings treated with TNFalpha alone. Levels of eNOS mRNA and protein were reduced
      despite improved vascular function after treatment with MG132. MG132 markedly
      suppressed mRNA levels of NADPH oxidase subunits and increased SOD1 expression.
      Superoxide production was reduced in rings incubated with MG132 in comparison to
      controls. TNFalpha-induced upregulation of the potent vasoconstrictor endothelin
      was abolished by MG132. SIGNIFICANCE: Proteasome inhibition prevents TNFalpha
      induced vascular dysfunction by reduction of superoxide production and
      suppression of endothelin levels. The balance between vasoconstriction and
      vasodilatation is shifted in favour of endothelium-dependent vasodilation.

PMID- 19409915
TI  - New insight into the non-neuronal cholinergic system via studies on chronically
      painful tendons and inflammatory situations.
AB  - For certain parts of the body, it is nowadays accepted that there is a
      cholinergic system that is not related to cholinergic innervation, i.e. a non
      neuronal cholinergic system. It might be argued that this system is of minor
      importance. New information obtained shows, however, that the non-neuronal
      cholinergic system is more widely distributed in the body than what is previously
      recognised. In recent studies, the existence of such a system has thus been shown
      for human tendons, especially in chronically painful situations
      (tendinopathy/tendinosis), in the synovial tissue of patients with rheumatoid
      arthritis and osteoarthritis, and in the mucosa of ulcerative colitis patients.
      There is evidence of both acetylcholine (ACh) production and a marked existence
      of muscarinic (M2) ACh receptors in these situations. The non-neuronal
      cholinergic system may be involved in the establishment of a 'cholinergic anti
      inflammatory pathway' and in proliferative and tissue reorganisation processes
      via autocrine/paracrine effects. The new information obtained suggests that this
      system plays an important functional role in chronically painful tendons and in
      inflammatory conditions. The findings of such a system in various parts of the
      body, when taken together, show that not only should the classical neuronal
      cholinergic system be considered in discussion of the cholinergic influences in
      the body. Additionally, the production of ACh in local cells in the tissues
      represents an important extra supply of the transmitter. ACh effects can be
      obtained whether or not there is a cholinergic innervation in the tissue.

PMID- 19409914
TI  - The 15-deoxy-Delta12,14-prostaglandin J2 inhibits LPS-stimulated AKT and NF
      kappaB activation and suppresses interleukin-6 in osteoblast-like cells MC3T3E-1.
AB  - AIMS: Periodontitis is a chronic inflammatory disease that results in gingival
      inflammation and periodontal tissue destruction and is accompanied by alveolar
      bone resorption and eventual tooth loss. We examined the effect of 15-deoxy
      Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) on periodontitis by inhibiting the
      production of interleukin-6 (IL-6). MAIN METHODS: Osteoblast-like cells MC3T3E-1
      were pretreated with 15d-PGJ(2) before being incubated with lipopolysaccharide
      (LPS), the effect of 15d-PGJ(2) on IL-6 production, expression and its regulatory
      mechanisms were studied by reverse transcription-polymerase chain reaction (RT
      PCR), Western blot, electrophoretic mobility shift assay (EMSA), and confocal
      laser scanning microscopy study. KEY FINDINGS: 15d-PGJ(2) inhibits LPS-stimulated
      IL-6 production in a concentration-dependent manner in osteoblast-like cells
      MC3T3E-1, without appreciable cytotoxicity. To further examine the mechanism
      responsible for the inhibition of IL-6 production by 15d-PGJ(2), we examined the
      effect of 15d-PGJ(2) on nuclear factor-kappaB (NF-kappaB) activation and the
      phosphorylation of protein kinase B (Akt). 15d-PGJ(2) treatment clearly reduced
      the DNA binding activity of NF-kappaB in LPS-stimulated osteoblast-like cells
      MC3T3E-1, an effect that was mediated by inhibiting the degradation of inhibitor
      kappaB (IkappaB) and nuclear translocation of NF-kappaB p65 subunit. In addition,
      15d-PGJ(2) attenuated the LPS-mediated Akt pathway. These effects of 15d-PGJ(2)
      were not abrogated by the PPARgamma antagonist, GW9662, indicating that they are
      PPARgamma-independent actions. SIGNIFICANCE: These results suggest that 15d
      PGJ(2) possess a potent suppressive effect on inflammatory responses of
      osteoblast-like cells MC3T3E-1 via the Akt and NF-kappaB pathways independent of
      PPARgamma and suggest that this compound may offer some insight into the
      development of a new therapeutic approach to the prevention and treatment of
      periodontal diseases.

PMID- 19409916
TI  - Capillary injury in the ischemic brain of hyperlipidemic, apolipoprotein B-100
      transgenic mice.
AB  - AIMS: Apolipoprotein B-100 (apoB-100) has been implicated in hyperlipidemia,
      which contributes to the pathogenesis of vascular disorders. Our aim was to
      investigate whether the expression of human apoB-100 in transgenic mice and/or a
      high-cholesterol diet cause cerebral microvascular lesions, and whether these
      conditions augment ischemia-related capillary damage. MAIN METHODS: Human apoB
      100 overexpressing transgenic (Tg(apoB-100), n=23) and wild-type mice (C5/B6, Wt,
      n=26) were supplied with standard or 2% cholesterol-enriched diet for 17-19
      weeks. Cerebral ischemia was induced by unilateral common carotid artery
      occlusion. Cortical samples were embedded for electron microscopy. Microvascular
      density (number of microvascular profiles/examined area), lumen diameter, the
      swelling of astrocytic endfeet, the occurrence of endothelial microvilli
      (affected capillaries expressed as ratio of all capillaries encountered), and the
      ratio of intact capillaries (devoid of all the above pathology) were calculated.
      KEY FINDINGS: The expression of apoB-100 coincided with decreased cortical
      microvascular density (195+/-7 vs. 223+/-8 vessels/mm(2), vs. Wt; P<0.008) and
      increased capillary lumen diameter (3.16+/-0.5 vs. 2.88+/-0.6 microm, vs. Wt;
      P<0.001). Cerebral ischemia promoted the swelling of perivascular astrocytes
      (62.1+/-4.2 vs. 36.5+/-4.0%, vs. contralateral, Wt; P<0.001), and reduced the
      ratio of intact capillaries (32.1+/-5.6 vs. 65.2+/-3.7%, vs. contralateral, Wt;
      P<0.001). Hyperlipidemia did not exacerbate the injury. SIGNIFICANCE: The
      overexpression of human apoB-100 alters the density of the microvascular network
      and the diameter of capillaries, which may compromise cerebrovascular reactivity
      during ischemia.

PMID- 19409917
TI  - The natural diterpenoid ovatodiolide induces cell cycle arrest and apoptosis in
      human oral squamous cell carcinoma Ca9-22 cells.
AB  - AIMS: Oral squamous cell carcinoma (OSCC) is a common worldwide malignancy and
      there has been little improvement in survival rates in recent decades.
      Ovatodiolide, a diterpenoid from a Chinese herb, has been reported to exhibit
      cytotoxicity against several human cancer cell lines. In the present study, the
      mechanism of action of ovatodiolide was further investigated in the p53 mutant
      OSCC cell line Ca9-22. MAIN METHODS: The effect of ovatodiolide on cell viability
      was examined by MTT assay. Cell cycle analysis, DNA fragmentation, and reactive
      oxygen species (ROS) were investigated by flow cytometry. Caspases and other
      regulatory molecules were studied by Western blotting. KEY FINDINGS: Treatment of
      Ca9-22 cells with ovatodiolide led to cell cycle arrest at G2/M phase.
      Ovatodiolide treatment also induced apoptosis, as indicated by caspase
      activation, DNA fragmentation, and poly (ADP-ribose) polymerase (PARP) cleavage.
      By using specific inhibitors of caspase-9 and -8, we demonstrated that
      ovatodiolide-induced apoptosis is dependent on both intrinsic and extrinsic
      pathways. The action of ovatodiolide was correlated with a rapid and sustained
      increase in ROS production and down-regulation of FLICE inhibitory protein
      (FLIP), which is an endogenous caspase-8 inhibitor and is sensitive to
      intracellular redox status. Pretreatment of Ca9-22 cells with N-acetylcysteine, a
      thiol antioxidant, abolished all of ovatodiolide-induced effects, including ROS
      generation, down-regulation of FLIP, caspase activation, apoptosis as well as
      cell cycle arrest. SIGNIFICANCE: Our results suggest that ovatodiolide causes
      cell cycle arrest and apoptosis in Ca9-22 cells through disturbance of
      intracellular redox balance. Furthermore, ovatodiolide may serve as a lead
      compound for developing new anticancer drugs.

PMID- 19409918
TI  - A point process driven multiple change point model: a robust resistant approach.
AB  - Helicases are a class of enzymes involved in Ribonucleic Acid (RNA) metabolism.
      In this work a statistical method is proposed to analyze the individual
      mechanistic cycle of these motor proteins which are crucial to the understanding
      of their cellular functions. The RNA unwinding by NS3 helicase is hypothesized to
      occur in a series of discrete steps and the steps themselves occurring in
      accordance to an underlying point process. A point process driven multiple change
      point model is proposed to model the RNA unwinding mechanism. The methods are
      portable to other areas of applications as well. Algorithms based on robust
      resistant statistical procedures are proposed to detect the change points. Both
      sequential and a posteriori change point models are considered. The relevant
      parameters of interest are estimated using a maximum likelihood approach.
      Simulations are performed to assess the performance of the methodology.

PMID- 19409919
TI  - Effects of age, viewing distance and target complexity on static ocular
      counterroll.
AB  - The ocular counterroll (OCR) reflex generates partially compensatory torsional
      eye movements during static head roll tilt. We assessed the influence of age,
      viewing distance and target complexity on the OCR across the age span (13-63
      years; n=47), by recording eye movements during head-on-body roll tilt (0+/-40
      degrees in 5 degrees steps) while subjects viewed simple vs. complex targets at
      0.33 and 1m. We found that subjects > or = 31 years had lower gains than those <
      or =30 years, but only for far targets. Consistent with prior reports, far
      targets elicited higher OCR gains than near targets, and target complexity had no
      effect on gains, suggesting that visual input is primarily used to maintain
      vergence during OCR.

PMID- 19409920
TI  - Deficits in adult prefrontal cortex neurons and behavior following early post
      natal NMDA antagonist treatment.
AB  - The prefrontal cortex (PFC) is associated with higher cognitive functions
      including attention and working memory and has been implicated in the regulation
      of impulsivity as well as the pathology of complex mental illnesses. N-methyl D
      aspartate (NMDA) antagonist treatment with dizocilpine induces cell death which
      is greatest in the frontal cortex on post-natal day seven (P7), however the long
      term structural and behavioral effects of this treatment are unknown. This study
      investigates both the acute neurotoxicity of P7 dizocilpine and the persistent
      effects of this treatment on pyramidal cells and parvalbumin interneurons in the
      adult PFC, a brain region involved in the regulation of impulsivity. Dizocilpine
      treatment on P7 increased cleaved caspase-3 immunoreactivity (IR) in the PFC on
      P8. In adult mice (P82), P7 dizocilpine treatment resulted in 50% fewer
      parvalbumin-positive interneurons (p<0.01) and 42% fewer layer V pyramidal
      neurons (p<0.01) in the PFC. Double immunohistochemistry revealed cleaved caspase
      3 IR in both GAD67 IR interneurons and GAD67 (-) neurons. Following dizocilpine
      treatment at P7, adults showed reduced time in the center of the open field
      suggesting increased anxiety-like behavior. These findings indicate that early
      brain insults affecting glutamatergic neurotransmission lead to persistent brain
      pathology that could contribute to impulsivity and cognitive dysfunction.

PMID- 19409921
TI  - Antinociceptive activity of Paederosidic Acid Methyl Ester (PAME) from the n
      butanol fraction of Paederia scandens in mice.
AB  - Antinociceptive activity of Paederosidic Acid Methyl Ester (PAME), a chemical
      compound isolated from the n-butanol fraction of Paederia scandens, was evaluated
      in mice using chemical and thermal models of nociception. PAME given by
      intraperitoneal injection at doses of 20, 40 and 60 mg/kg produced significant
      inhibitions on chemical nociception induced by intraperitoneal acetic acid,
      subplantar formalin or capsaicin injections and on thermal nociception in the
      tail-flick test and the hot plate test. In the pentobarbital sodium-induced sleep
      time test and the open-field test, PAME neither significantly enhanced the
      pentobarbital sodium-induced sleep time nor impaired the motor performance,
      indicating that the observed antinociceptive activity of PAME was unlikely due to
      sedation or motor abnormality. Core body temperature measurement showed that PAME
      did not affect temperature within a 2-h period. Moreover, PAME-induced
      antinociception in the hot plate test was insensitive to naloxone or nimodipine
      but significantly antagonized by L-NAME (N (G)-nitro-L-arginine methyl ester),
      methylene blue and glibenclamide. These results suggested that PAME-produced
      antinociception was possibly related to the pathway of NO-cGMP-ATP sensitive K(+)
      channels, which merited further studies regarding the precise site and mechanisms
      of action.

PMID- 19409922
TI  - Gene-environment interactions resulting in risk alcohol drinking behaviour are
      mediated by CRF and CRF1.
AB  - Both genetic and environmental influences are known to influence an individuals'
      vulnerability to the misuse of alcohol. One of the most relevant environmental
      risk factors for alcoholism is that of stress. This review aims to examine the
      role of the biological stress systems in the etiology of alcoholism, with a focus
      on corticotrophin releasing factor (CRF) and its receptor CRF1. CRF is reviewed
      in the context of the biological stress systems within which it acts such as the
      HPA-axis, the noradrenergic system and the central and medial amygdale. These
      systems are examined in more detail by reviewing their genetic and molecular
      components in both humans and animals. It is concluded from the findings of the
      studies discussed in this review that CRF has a central role in the modulation of
      the stress response and that genetic variations in CRF or CRF1 may confer a
      susceptibility to alcoholism which is, in part, mediated by life stressors.
      Together these neurobiological, animal and human data suggest a role for CRF when
      developing treatment modalities for alcoholism alongside a pharmacogenetic
      approach to identify subtypes of patients which would benefit from these
      treatments or interventions.

PMID- 19409923
TI  - Heavy drinking is associated with deficient response inhibition in women but not
      in men.
AB  - Poor response inhibition has been associated with a wide range of problem
      behaviours, including addictive behaviours, and could represent a general
      vulnerability factor. Standard tests of response inhibition have used neutral
      stimuli. Here we tested whether a deficit in response inhibition in heavy
      drinkers would be stronger for stimuli related to their problem (alcohol) or not.
      Response inhibition was assessed with a stop signal task, using four classes of
      pictures: alcohol-related, soft drinks, erotic (control appetitive categories)
      and neutral pictures. Participants were 32 heavy and 32 light drinkers. An equal
      amount of men and women were tested in both drinking groups, in view of recent
      studies reporting that response disinhibition may be most pronounced in heavy
      drinking women. Main results were first that no domain-specific differences in
      response inhibition were found in both groups. Second, heavy drinking females
      showed stronger response inhibition deficits than other groups. Results are
      discussed in light of a possible gender difference in response inhibition as a
      risk factor for addictive behaviours.

PMID- 19409925
TI  - Aggregation of human serum albumin during a thermal viral inactivation step.
AB  - A terminal pasteurization step has been used for some plasma-derived protein
      products such as human serum albumin (HSA), which consists of heating the protein
      in solution at 60 degrees C for 10 h. Native and denaturing SDS-PAGE and dynamic
      light scattering were used to follow the stability of HSA during this process. It
      appears that a thermally unstable fraction, comprised primarily of haptoglobin,
      is involved in the formation of soluble aggregates of HSA. Therefore, it appears
      that aggregation during heat treatment is not due to conformational instability
      of HSA itself, but arises from unfolding of a thermally labile protein impurity.
      As haptoglobin aggregates, it entraps some HSA, which is present at much higher
      concentrations. This study emphasizes that, in a complex mixture of naturally
      occurring proteins, one thermally labile species can trigger aggregation of more
      stable proteins.

PMID- 19409924
TI  - Hematocrit and the risk of coronary heart disease mortality in the TAMRISK study,
      a 28-year follow-up.
AB  - OBJECTIVE: To evaluate whether hematocrit (HCT) is associated with coronary heart
      disease (CHD) mortality in men over 55 years of age in Finland. METHODS: Health
      survey data were recorded in 1980 from 670 men, aged 55 years. The causes of
      deaths during a 28-year follow-up were obtained from official records.
      Statistical comparisons were done by Cox proportional hazard regression model
      after dividing the men into two groups, one with HCT<50% and the other, HCT> or
      =50%. RESULTS: There were altogether 412 deaths of all causes, including 140 from
      CHD. In men having HCT<50%, the crude CHD mortality rate per 10,000 population
      was 2203, while in men with HCT> or =50%, the corresponding figure was 4255. Men
      with HCT> or =50% were 2.4 times (95% CI 1.6-3.5) more likely to die from CHD
      than were men with HCT<50%. After adjusting for established coronary risk
      factors, the increased risk remained 1.8-fold (95 % CI, 1.1-2.7). CONCLUSIONS:
      Borderline polycythemia was associated with increased CHD mortality. The cut-off
      value in our study was > or =50%, proposing that for men over 55 years of age
      such HCT levels might be an additional risk factor.

PMID- 19409926
TI  - Influence of temperature, salinity and E. coli tissue content on immune gene
      expression in mussel: results from a 2005-2008 survey.
AB  - Several bivalves, including mussels, suffered from mortalities particularly in
      summer. To look for the possible effect of environmental parameters on immune
      capacities, Mytilus galloprovincialis were collected monthly from August 2005 to
      July 2008 from the Palavas Laguna, French Mediterranean coast. Q-PCR was used to
      quantify the expression of three antimicrobial peptide genes (defensin, mytilin B
      and myticin B), in addition to lysozyme and HSP70. House keeping gene was 28S
      rRNA. Defensin, myticin B and lysozyme appeared more expressed in spring-summer
      than in winter. In contrast, HSP70 expression was higher in winter. Statistical
      studies using principal component analysis (PCA) and multiple regression models
      revealed positive influence of temperature on 28S rRNA, defensin, myticin B and
      lysozyme expressions, but not on mytilin B and HSP70. The positive influence was
      significant for defensin and lysozyme expression, but relationships cannot be
      quantified. Similarly, salinity appeared to influence defensin expression, but
      this relationship cannot be quantified neither. E. coli tissue content appeared
      without influence. Consequently, there was no clear relationship between
      environmental parameters and immune-related gene expressions, demonstrating anti
      infectious capabilities cannot be evaluated using only the expression of such
      genes as markers.

PMID- 19409927
TI  - Ghrelin - Defender of fat.
AB  - With one quarter of the population of the Western world now considered obese, it
      is essential that we understand the factors giving rise to elevated fat
      deposition. This review summarizes the cellular and molecular mechanisms
      governing the volume of white adipose tissue (WAT), and outlines the
      physiological signals that regulate these processes. Particular attention is
      given to the role of the gastric hormone, ghrelin, describing its actions in
      general and presenting detailed evidence of its role in regulating adipocyte
      biology. Combining this evidence with an analysis of the factors governing
      ghrelin secretion, leads to the hypothesis that during periods of food
      deprivation ghrelin acts as an energy deficit signal, defending the fat stored in
      responsive WAT against the forces of utilization. This scenario has clear
      implications for programmes of sustainable weight loss.

PMID- 19409928
TI  - Potassium channel expression in human CD4+ regulatory and naive T cells from
      healthy subjects and multiple sclerosis patients.
AB  - The membrane potential of human T cells is regulated by two potassium channels:
      the voltage-gated K(V)1.3 and the Ca2+-activated K(Ca)3.1. These two channels are
      essential for efficient antigenic activation and proliferation of T cells and are
      expressed at different levels in naive, central memory and effector memory T
      cells. This provides the opportunity to inhibit the proliferation of the targeted
      subtype by channel-specific blocking compounds. Regulatory T cells (Tregs) also
      represent a unique subtype of T cells that perform highly specialized tasks in
      controlling immune responses, which raises the possibility that they too have a
      distinctive channel expression pattern. Using whole-cell patch-clamp we tested
      this hypothesis and determined the ion channel expression of
      CD4+CD25(hi)CD127(lo) regulatory and CD4+CD25(lo)CD127(hi) naive T cells from the
      peripheral blood of healthy volunteers and multiple sclerosis (MS) patients
      sorted by flow cytometry. We have found that naive and Treg cells from healthy
      controls expressed equal numbers of K(V)1.3 channels, while Tregs had a greater
      membrane surface as assessed by capacitance measurements, and consequentially
      lower channel density than naive cells, indicating an "incomplete activation
      state" of Tregs. In contrast, Tregs from MS patients had fewer K(V)1.3 channels
      than naive cells and there was no difference in the membrane capacitance or
      channel density between the two subtypes of cells. The expression level of
      K(Ca)3.1 channels was similar in all cell subsets. The observed differences in
      K(V)1.3 channel expression density may contribute to the varying responses upon
      antigenic stimulation by these cell types in health and disease.

PMID- 19409929
TI  - Differential diagnosis of orf viruses by a single-step PCR.
AB  - The complete nucleotide sequence of the A32L gene (named after vaccinia virus,
      corresponding with open reading frame 108 of the orf virus and encoding an
      ATPase) of the orf virus was studied using samples of orf virus from infected
      goats, which were collected from six outbreaks in central Taiwan. DNA sequence
      analysis of the A32L genes of these and isolates from other countries showed
      sequence heterogeneity (base pair variation and deletion) in the 3'-terminal
      regions. This finding led to the development of a polymerase chain reaction (PCR)
      method for the rapid differential diagnosis of orf virus infections, and the
      results demonstrated that this was an easy and reliable method for genotyping of
      orf viruses.

PMID- 19409931
TI  - Induction of multiple pro-inflammatory cytokines by respiratory viruses and
      reversal by standardized Echinacea, a potent antiviral herbal extract.
AB  - Several viruses associated with upper respiratory diseases have been shown to
      stimulate the secretion of pro-inflammatory cytokines, including chemokines,
      sometimes in the absence of viral cytopathology. We evaluated the ability of a
      standardized preparation of the popular herbal medicine Echinacea (Echinaforce,
      an ethanol extract of herb and roots of E. purpurea, and containing known
      concentrations of marker compounds) to inhibit the viral induction of various
      cytokines in a line of human bronchial epithelial cells (BEAS-2B), and in two
      other human cell lines. All of the viruses tested, rhinoviruses 1A and 14,
      influenza virus, respiratory syncytial virus, adenovirus types 3 and 11, and
      herpes simplex virus type 1, induced substantial secretion of IL-6 and IL-8
      (CXCL8), in addition to several other chemokines, depending on the virus,
      although only viable viruses were able to do this. In every case however
      Echinacea inhibited this induction. The Echinacea preparation also showed potent
      virucidal activity against viruses with membranes, indicating the multi
      functional potential of the herb. These results support the concept that certain
      Echinacea preparations can alleviate "cold and flu" symptoms, and possibly other
      respiratory disorders, by inhibiting viral growth and the secretion of pro
      inflammatory cytokines.

PMID- 19409932
TI  - Automated analysis of behavior in zebrafish larvae.
AB  - Zebrafish larvae have become a popular model system to examine genetic and
      environmental factors that affect behavior. However, studying complex behavior in
      large numbers of fish larvae can be challenging. The present study describes a
      novel high-resolution imaging system that is unique in its ability to
      automatically analyze the location and orientation of zebrafish larvae in
      multiwell plates. The system revealed behaviors in zebrafish larvae that would
      have been missed by more manual approaches, including a preference to face a
      threatening stimulus from a distance and a clockwise orientation in a two-fish
      assay. The clockwise orientation of the larvae correlates with a clockwise
      orientation of molecular structures during early development. Larvae with
      reversed embryonic asymmetries display a counter-clockwise orientation in the two
      fish assay, suggesting that embryonic asymmetry and chiral behavior are regulated
      by the same developmental mechanisms. The developed imaging techniques may be
      used in large-scale screens to identify genes, pharmaceuticals, and environmental
      toxicants that influence complex behaviors.

PMID- 19409930
TI  - Lac-regulated system for generating adenovirus 5 vaccine vectors expressing
      cytolytic human immunodeficiency virus 1 genes.
AB  - Adenovirus (Ad) vectors have been developed as human immunodeficiency-1 (HIV-1)
      vaccine vectors because they consistently induce immune responses in preclinical
      animal models and human trials. Strong promoters and codon-optimization are often
      used to enhance vaccine-induced HIV-1 gene expression and immunogenicity.
      However, if the transgene is inherently cytotoxic in the cell line used to
      produce the vector, and is expressed at high levels, it is difficult to rescue a
      stable Ad HIV-1 vaccine vector. Therefore we hypothesized that generation of Ad
      vaccine vectors expressing cytotoxic genes, such as HIV-1 env, would be more
      efficient if expression of the transgene was down-regulated during Ad rescue. To
      test this hypothesis, a Lac repressor-operator system was applied to regulate
      expression of reporter luciferase and HIV-1 env transgenes during Ad rescue. The
      results demonstrate that during Ad rescue, constitutive expression of the Lac
      repressor in 293 cells reduced transgene expression levels to approximately 5% of
      that observed in the absence of regulation. Furthermore, Lac-regulation
      translated into more efficient Ad rescue compared to traditional 293 cells.
      Importantly, Ad vectors rescued with this system showed high levels of transgene
      expression when transduced into cells that lack the Lac repressor protein. The
      Lac-regulated system also facilitated the rescue of modified Ad vectors that have
      non-native receptor tropism. These tropism-modified Ad vectors infect a broader
      range of cell types than the unmodified Ad, which could increase their
      effectiveness as a vaccine vector. Overall, the Lac-regulated system described
      here (i) is backwards compatible with Ad vector methods that employ bacterial
      mediated homologous recombination, (ii) is adaptable for the engineering of
      tropism-modified Ad vectors, and (iii) does not require co-expression of
      regulatory genes from the vector or the addition of exogenous chemicals to induce
      or repress transgene expression. This system therefore could facilitate the
      development of Ad-based vaccine candidates that otherwise would not be feasible
      to generate.

PMID- 19409933
TI  - Does the learning deficit observed under an incremental repeated acquisition
      schedule of reinforcement in Ts65Dn mice, a model for Down syndrome, change as
      they age?
AB  - The Ts65Dn mouse is partly trisomic at chromosome 16 and is considered to be a
      valid mouse model of human Down syndrome. Prior research using an incremental
      repeated acquisition (IRA) schedule of reinforcement has revealed that there is a
      significant learning deficit in young, adult Ts65Dn mice compared to littermate
      controls. The purpose of this study was to examine whether this deficit changes
      during the life-span of these mice. In order to determine if changes in the
      deficit were caused by motoric or motivational deficiencies, a second group of
      mice was trained to respond under a performance version of the task (IRA-P). The
      IRA-P task required the same motor responses to produce the reinforcer, but no
      learning or acquisition was required. Data collected under the IRA task
      demonstrated that there was a significant learning impairment that persisted up
      to 24 months of age in the Ts65Dn mice compared to littermate controls. There was
      a significant decrease in the rate of responding and the number of milk
      presentations earned by the Ts65Dn mice after 19 months of age. However, during
      this time, response accuracy, which is independent of mobility and possibly
      motivation, did not decrease. Under the IRA-P schedule, there was no decrease
      observed in the number of milk presentations of either line as they aged, but the
      trend in the rate of responding of the Ts65Dn mice was similarly declining as the
      rate of responding observed in the Ts65Dn mice under the IRA task. These data
      indicate that the ability to learn in Ts65Dn mice does not decline with age as
      measured by the IRA task and suggests that perhaps Ts65Dn mice do not exhibit the
      same early onset Alzheimer's disease phenotype that is typically seen in human
      patients.

PMID- 19409934
TI  - Chronically elevated corticosterone in the dorsolateral bed nuclei of stria
      terminalis increases anxiety-like behavior.
AB  - We previously discovered that corticosterone administration into the amygdala
      increases anxiety-like behaviors in rats tested on an elevated plus maze. However
      the behavioral effects of elevated corticosterone in a functionally related
      structure, the bed nuclei of stria terminalis (BNST) are unknown. The current
      study examined the effects of corticosterone administration into the dorsolateral
      BNST on exploratory behavior on an elevated plus maze. Corticosterone reduced
      open arm exploration on the plus maze indicating an increase in anxiety-like
      behavior.

PMID- 19409935
TI  - Preferred chewing side-dependent two-point discrimination and cortical activation
      pattern of tactile tongue sensation.
AB  - Although tactile feedback from the tongue should contribute to habitual chewing,
      it is unclear how the sensation of the tongue and its projection to the central
      nervous system differ with regard to the preferred chewing side (PCS). The
      purpose of this study was to investigate (1) whether the sensory threshold of the
      tongue differed according to the side and (2) whether the pattern of hemispheric
      cortical activation by tactile tongue stimulation differed, with special
      attention to the PCS. Twelve healthy adults participated in the study. The PCS
      was determined with a mandibular kinesiograph. In the behavioral study, the mean
      thresholds for two-point discrimination (TPD) in the anterior, canine and
      posterior regions on both sides of the tongue, and those between PCS and non-PCS
      in each region were statistically compared. In the functional magnetic resonance
      imaging study, tactile stimulation was delivered to either side of the tongue
      with acrylic balls via a mandibular splint. The runs were measured with a T2*
      weighted gradient echo-type echo planar imaging sequence in a 1.5T scanner.
      Activated voxel numbers in the bilateral primary somatosensory cortex (S1) were
      statistically compared. The threshold of TPD increased in the order of the
      anterior, canine and posterior regions. Moreover, this threshold was
      significantly smaller on the PCS than on the non-PCS in both the canine and
      posterior regions. Moreover, the number of activated voxels in S1 contralateral
      to the PCS was significantly greater than that in S1 contralateral to the non
      PCS. The present study shows that the PCS is associated with asymmetric tactile
      sensation and cortical activation of the tongue. The sensory acuity of the tongue
      on the PCS may play an important role in functional coupling between the jaw and
      tongue to maximize the efficiency of chewing.

PMID- 19409936
TI  - Peripheral mechanisms in the control of appetite and related experimental
      therapies in obesity.
AB  - The function of the stomach and the gut hormonal responses to food ingestion
      constitute highly integrated homeostatic responses that maintain euglycemia and
      normal digestion. This intrinsic feedback involves vagal and hormonal mechanisms.
      Important signals such as GLP-1 and PYY that arise peripherally induce satiation
      and also delay gastric emptying or increase insulin secretion. Novel therapies
      are being developed to mimic or enhance these feedback mechanisms and to control
      appetite as a means to treat obesity.

PMID- 19409938
TI  - Single cell oil production by Mortierella alpina.
AB  - A filamentous fungus, Mortierella alpina 1S-4, was obtained, through extensive
      screening, as an potential producer of triacylglycerol containing C20
      polyunsaturated fatty acids (PUFAs) such as arachidonic acid. With this discovery
      as a starting point, we conducted employing methods from metabolic engineering
      and molecular biology for controlling cultures and breeding mutant strains. These
      parental and mutant strains are now used for large-scale production of a variety
      of PUFAs.

PMID- 19409939
TI  - Hofmeister effects: an explanation for the impact of ionic liquids on
      biocatalysis.
AB  - Ionic liquids (ILs) have shown potentials as a new reaction medium for
      biocatalysis, either as such or as an aqueous mixture. Their unique ionic nature
      is important in affecting the enzyme performance, and the Hofmeister effects
      provide a reasonable explanation for this. In this review, the impact of
      Hofmeister effects on enzyme performance in aqueous solution was first examined,
      concerning the specific ion effects on altering the bulk water properties,
      modifying the protein-water interactions, and interacting with the enzyme
      molecules; then the effect of IL cations and anions on enzyme activity and
      stability in aqueous IL mixtures was discussed, taking both kinetic and
      structural studies into consideration; and finally, our recent study regarding
      mushroom tyrosinase in the presence of ILs and their associated anions was used
      to illustrate the cooperative functioning of IL cations and anions in affecting
      enzyme performance, following the Hofmeister series. Design and use of water
      mimicking ILs composed of chaotropic cations and kosmotropic anions may
      facilitate the applications of ILs in biotransformations.

PMID- 19409937
TI  - Regulation of the formation and trafficking of vesicles from Golgi by PCH family
      proteins during chemotaxis.
AB  - Previous study demonstrated that WASP localizes on vesicles during Dictyostelium
      chemotaxis and these vesicles appear to be preferentially distributed at the
      leading and trailing edge of migrating cells. In this study, we have examined the
      role of PCH family proteins, Nwk/Bzz1p-like protein (NLP) and Syndapin-like
      protein (SLP), in the regulation of the formation and trafficking of WASP
      vesicles during chemotaxis. NLP and SLP appear to be functionally redundant and
      deletion of both nlp and slp genes causes the loss of polarized F-actin
      organization and significant defects in chemotaxis. WASP and NLP are colocalized
      on vesicles and interactions between two molecules via the SH3 domain of NLP/SLP
      and the proline-rich repeats of WASP are required for vesicle formation from
      Golgi. Microtubules are required for polarized trafficking of these vesicles as
      vesicles showing high directed mobility are absent in cells treated with
      nocodazole. Our results suggest that interaction of WASP with NLP/SLP is required
      for the formation and trafficking of vesicles from Golgi to the membrane, which
      might play a central role in the establishment of cell polarity during
      chemotaxis.

PMID- 19409940
TI  - Synergistic effects of chromosomal ispB deletion and dxs overexpression on
      coenzyme Q(10) production in recombinant Escherichia coli expressing
      Agrobacterium tumefaciens dps gene.
AB  - For biotechnological production of coenzyme Q(10) (CoQ(10)) in recombinant
      Escherichia coli, three genetic manipulations were performed: heterologous
      expression of decaprenyl diphosphate synthase (Dps) from Agrobacterium
      tumefaciens, deletion of endogenous octaprenyl diphosphate synthase (IspB), and
      overexpression of 1-deoxy-d-xylulose synthase (Dxs). Expression of the dps gene
      and deletion of the ispB gene in E. coli BL21(DE3)DeltaispB/pAP1 allowed
      production of CoQ(10) only. Furthermore, coexpression of the dxs gene increased
      the specific content of CoQ(10) from 0.55-0.89mgg(-1) to 1.40mgg(-1). For mass
      production of CoQ(10), fed-batch fermentation of E. coli
      BL21(DE3)DeltaispB/pAP1+pDXS was carried out in a defined medium with 20gl(-1)
      initial glucose and by the glucose-feeding strategy of pH-stat. Finally, 99.4mgl(
      1) CoQ(10) concentration, 1.41mgg(-1) specific CoQ(10) content and 3.11mgl(-1)h(
      1) productivity were obtained in 33h of the fermentation, which were 78, 1.9, and
      19 times higher than those for E. coli BL21(DE3)/pAP1 without the ispB deletion
      and dxs overexpression.

PMID- 19409941
TI  - Ligands for mixed-mode protein chromatography: Principles, characteristics and
      design.
AB  - Mixed-mode chromatography is a chromatographic method that utilizes more than one
      form of interactions between the stationary phase and the solutes in a feed
      stream. Compared with other types of chromatography, mixed-mode chromatography is
      advantageous in its salt-independent adsorption, facile elution by charge
      repulsion, and unique selectivity. Hence, it has already proved beneficial for
      the separation of proteins as well as other purposes. In this article, mixed-mode
      ligands for protein purification have been reviewed. These ligands usually have
      an aliphatic or aromatic group as the hydrophobic moiety and an amino, carboxyl
      or sulfonic group as the ionic moiety. Heterocyclic groups are good ligand
      candidates for their unique hydrophobicity and dissociation property. Hydrogen
      bonding groups also have influences on the performance of mixed-mode adsorbents.
      These principles should be considered in the screening and design of mixed-mode
      ligands. Strategies for the design of synthetic affinity ligands, especially the
      bioinformatics and combinatorial methods, may be adopted for mixed-mode ligand
      design. More efforts are needed for the development of rational design and
      screening methods for mixed-mode protein ligands by sophisticated computational
      and experimental approaches.

PMID- 19409942
TI  - The detection of Bovine Papillomavirus type 1 DNA in flies.
AB  - BPVs are double stranded DNA viruses that can infect several species other than
      the natural host, cattle, including equids. In equids, BPV-1, and, less commonly
      BPV-2, infection gives rise to fibroblastic tumours of the skin. Whilst a causal
      relationship between BPV-1/2 and equine sarcoids is now well established, how the
      disease is transmitted is not known. In this study we show BPV-1 DNA can be
      detected in flies trapped in the proximity of sarcoid-affected animals. Sequence
      analysis of the BPV-1 LCR from flies indicates that flies harbour BPV-1 LCR
      sequence variants II and IV which are commonly detected in equine sarcoids. These
      data suggest that flies may be able to transmit BPV-1 between equids.

PMID- 19409943
TI  - Synergistic interaction between the Potyvirus, Turnip mosaic virus and the
      Crinivirus, Lettuce infectious yellows virus in plants and protoplasts.
AB  - Lettuce infectious yellows virus (LIYV), the type member of the genus Crinivirus
      in the family Closteroviridae, is specifically transmitted by the sweet potato
      whitefly (Bemisia tabaci) in a semipersistent manner. LIYV infections result in a
      low virus titer in plants and protoplasts, impeding reverse genetic efforts to
      analyze LIYV gene/protein functions. We found that synergistic interactions
      occurred in mixed infections of LIYV and Turnip mosaic virus (TuMV) in Nicotiana
      benthamiana plants, and these resulted in enhanced accumulation of LIYV.
      Furthermore, we examined the ability of transgenic plants and protoplasts
      expressing only the TuMV P1/HC-Pro sequence to enhance the accumulation of LIYV.
      LIYV RNA and protein titers increased by as much as 8-fold in these plants and
      protoplasts relative to control plants. LIYV infections remained phloem-limited
      in P1/HC-Pro transgenic plants, suggesting that enhanced accumulation of LIYV in
      these plants was due primarily to increased replication efficiency, not to
      greater spread.

PMID- 19409944
TI  - Genetic structure and variability of virus populations in cross-protected
      grapevines superinfected by Grapevine fanleaf virus.
AB  - Recombination was assessed in a vineyard site in which grapevines cross-protected
      with mild strains GHu of Grapevine fanleaf virus (GFLV) or Ta of Arabis mosaic
      virus (ArMV) were superinfected with GFLV field isolates following transmission
      by the nematode vector Xiphinema index. The genetic structure and variability
      within RNA2 of isolates from grapevines co-infected with GFLV field isolates and
      either GFLV-GHu or ArMV-Ta were characterized to identify intra- and interspecies
      recombinants. Sequence analysis and phylogenetic relationships inferred
      intraspecies recombination among GFLV field isolates but not between field
      isolates and GFLV-GHu. SISCAN analysis confirmed a mosaic structure for two GFLV
      field isolates for which recombination sites were located in the movement protein
      and coat protein genes. One of the recombinants was found in eight grapevines
      that were in close spatial proximity within the vineyard site, suggesting its
      transmission by X. index. No interspecies recombination was detected between GFLV
      field isolates and ArMV-Ta. Altogether, our findings suggest that mild protective
      strains GFLV-GHu and ArMV-Ta did not assist the emergence of viable recombinants
      to detectable level during a 12-year cross-protection trial. To our knowledge,
      this is the first extensive characterization of the genetic structure and
      variability of virus isolates in cross-protected plants.

PMID- 19409945
TI  - Characterization of signals that dictate nuclear/nucleolar and cytoplasmic
      shuttling of the capsid protein of Tomato leaf curl Java virus associated with
      DNA beta satellite.
AB  - Transport of the viral genome into the nucleus is an obligatory step in the
      replication cycle of geminiviruses. Capsid proteins (CPs) of geminiviruses are
      multifunctional proteins thought to be involved in this process. The CP of
      monopartite geminiviruses is absolutely essential for virus movement. To more
      precisely examine the role of CP, we have constructed a series of single and
      double deletions into the coding sequence of Tomato leaf curl Java virus
      (ToLCJAV) CP and examined sub-cellular localization using transient expression of
      GFP fusion proteins. In this report, the domains of the CP encoded by ToLCJAV
      localized in the nucleus/nucleolus and cytoplasm in transfected cells were
      mapped. Deletion analysis revealed that the Arg-rich cluster from amino acids
      (aa) (16)KVRRR(20) in the N-terminal region of CP functioned as nuclear/nucleolar
      localization signals (NLSs). The region from aa (52)RKPR(55) contained basic
      amino acid cluster was capable to redirect the CP to the nucleus. Further, both
      transient expression and yeast hybrid assays demonstrated that CP was capable of
      shuttling between the nucleus and cytoplasm of the cell. Deletion mutant analysis
      revealed that this property was attributed to a nuclear export signal (NES)
      sequence consisted of aa ((245)LKIRIY(250)) reside at C-terminal part of CP. This
      hydrophobic region caused transport of GFP to the cytoplasm. However, ToLCJAV CP
      NLSs and NES show peculiarities in the number and position of basic residues.
      Taken together, these results demonstrated that ToLCJAV CP shuttles between the
      nucleus and cytoplasm, such an activity homolog to bipartite geminivirus BV1 ORF.

PMID- 19409946
TI  - HIV-1 clade C env clones obtained from an Indian patient exhibiting expanded
      coreceptor tropism are presented with naturally occurring unusual amino acid
      substitutions in V3 loop.
AB  - HIV-1 subtype C is predominantly circulating in India and has been reported to be
      strictly CCR5 tropic irrespective of disease stages. In the present study, we
      examined env clones obtained from a late stage Indian patient with a history of
      multiple sexual partners and opportunistic infections for coreceptor usage and V3
      loop sequence. The env clones were found to exploit several coreceptors in
      addition to CCR5 in a cell-associated and cell-free manner. Analysis of V3 loop
      sequence revealed that the NARI-VB105 env clones were presented with unique amino
      acid substitutions with GPGR motif, atypical of clade C envelope. Further genetic
      analysis showed the V3 sequences albeit belonging to subtype C; however clustered
      distinctly to that of other clade C envelopes originated in different
      geographical regions. Modelling data revealed that NARI-VB105 V3 loop contained
      several basic residues giving rise a high net positive charge of +8 to these
      envelopes.

PMID- 19409947
TI  - Tiger frog virus can infect zebrafish cells for studying up- or down-regulated
      genes by proteomics approach.
AB  - Tiger frog virus (TFV), a member of the iridovirus family, causes high mortality
      of cultured tiger frog tadpoles in southern China. To better understand TFV
      infection and its interaction with host cells, zebrafish embryonic fibroblast
      (ZF4) cells, a stable polyploid cell line with most clear genetic map, was used
      for our present study. Our results showed that TFV caused typical lytic plaque
      forming cytopathic effect (CPE) and that various stages of viral proliferation
      were observed using electron microscopy and indirect immunofluorescence assay.
      Two-dimensional electrophoresis also showed that some cellular proteins were
      differentially expressed in the ZF4 cells infected with TFV. A total of 10
      proteins were identified using the matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) technique, including 7 that were
      up-regulated and 3 that were down-regulated after infection. Among the 10
      identified proteins, alterations in Hsp90 and alpha-tubulin expression were
      further confirmed by Western blot analysis. Furthermore, reorganization of
      microtubules was also observed in TFV-infected cells and can probably be
      attributed to the overexpression of translationally controlled tumor protein. The
      present study is the first attempt to reveal cellular responses to TFV infection
      by proteomics. The results suggest that the ZF4 cell line could be used as a
      model to study TFV infection.

PMID- 19409949
TI  - Airborne asbestos exposure during light aircraft brake replacement.
AB  - Asbestos containing materials are a component of many vehicle brake systems,
      including those found in some light aircraft. To characterize the asbestos
      exposure that results from the installation and maintenance of these components,
      an aircraft fitted with asbestos containing brake pads had brake changes
      performed while both area and personal air samples were taken. The brake changing
      process took place in a closed, unventilated aircraft hanger and all operations
      were performed according to the manufacturer's recommended procedure. Personal
      air samples did not detect any measurable amount of asbestos fibers during the
      brake changing or subsequent cleanup procedures. Analysis of personal samples
      (n=9) using phase contrast microscopy indicated airborne fiber concentrations at
      or below 0.003f/ml as 8-h time weighted averages (TWAs) and less than 0.069f/ml
      averaged over 28-30min sampling periods. Airborne chrysotile fibers were detected
      by two area air samples with fiber concentrations remaining at or below
      0.0013f/ml over an 8-h TWA. These results indicate that normal brake changing
      work practices on aircraft with asbestos containing brake pads does not produce a
      harmful level of asbestos exposure for aircraft mechanics.

PMID- 19409948
TI  - Sm21.6 a novel EF-hand family protein member located on the surface of
      Schistosoma mansoni adult worm that failed to induce protection against challenge
      infection but reduced liver pathology.
AB  - Schistosomiasis continues to be a significant public health problem that affects
      200 million people worldwide. This is one of the most important parasitic
      diseases, and one whose effective control is unlikely in the absence of a
      vaccine. In this study, we have isolated a cDNA clone encoding the Schistosoma
      mansoni Sm21.6 protein that has 45% and 44% identity with Sm22.6 and Sj21.7 EF
      hand containing antigens, respectively. Confocal microscopy analysis revealed
      that Sm21.6 is a membrane-associated protein localized on the S. mansoni adult
      worm. Mouse immunization with rSm21.6 induced a mixed Th1/Th2 cytokine profile
      and no protection against infection. However, vaccination with rSm21.6 reduced by
      28% of liver granuloma numbers, 21% of granuloma area and 34% of fibrosis.
      Finally, rSm21.6 was recognized by sera from individuals resistant to reinfection
      compared with patients susceptible to reinfection and this molecule should be
      further studied as potential biomarker for disease resistance. In conclusion,
      Sm21.6 is a new tegument protein from S. mansoni that plays an important role in
      reducing pathology induced by parasite infection.

PMID- 19409950
TI  - Verbal but not performance IQ is highly correlated to externalizing behavior in
      boys with ADHD carrying both DRD4 and DAT1 risk genotypes.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is often associated
      with reduced IQ and high levels of externalizing behavior (EB). This study tested
      if DRD4 7-repeat allele and DAT1 10-repeat allele homozygosity interact in
      modulating correlations between IQ and EB in affected boys. METHODS: Boys (n=130)
      between 6 and 12 years of age diagnosed with ADHD were included in the study. IQ
      and EB were assessed by WISC-III and Child Behavioral Checklist, respectively.
      The 40 bp variable number tandem repeat (VNTR) of the DAT1 gene and the 48 bp
      VNTR of the DRD4 gene polymorphisms were genotyped and 4 subgroups were defined
      by the presence/absence of the DRD4 7-repeat allele and by the presence/absence
      of the DAT1 10/10 genotype. Correlation coefficients were compared using the
      Fisher's Z transformation and regression lines by a Potthoff analysis. RESULTS:
      In the total sample, all correlation coefficients between EB score and IQ were
      non significant. Also, no differences in IQ were observed between the 4 genotype
      groups. However, different pattern of correlations between IQ and EB score
      appeared. In boys carrying no or only one genetic risk, IQ and EB score were
      uncorrelated while in children carrying both risk factors, negative and
      significant correlations emerged. Notably, correlation of EB to verbal IQ was
      strong (r=-0.71) and highly significant (P<0.01) in boys carrying both risk
      alleles. All pair-wise comparisons of correlation coefficients were significant
      for EB-verbal IQ correlation. Test of coincidence of regression lines did not
      show significant differences. CONCLUSIONS: A specific domain of IQ, namely the
      verbal quotient is highly correlated to the level of EB in boys with ADHD
      carrying both dopaminergic risk genotypes. Further investigations are required to
      replicate these results and determine specificity to ADHD.

PMID- 19409951
TI  - Brain-derived neurotrophic factor plasma levels in patients suffering from post
      traumatic stress disorder.
AB  - In both animals and humans, stress has been demonstrated to reduce the expression
      of the Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin (NT) which
      promotes the proliferation, survival and differentiation of neurons. Although
      traumatic events have been found to be associated with lower BDNF plasma levels
      in affective disorders, no study has explored this parameter in patients with
      post-traumatic stress disorder (PTSD). We, therefore, measured BDNF plasma level
      in 18 patients with PTSD and in 18 healthy control subjects. Diagnoses were
      assessed by the Structured Clinical Interview for DSM-IV, while the specific
      symptoms were examined in the patients by means of the Impact of Event Scale for
      PTSD and the traumas experienced were assessed by using the Life Events
      Checklist. BDNF plasma levels were evaluated by means of a standardized Elisa
      method. The results, while showing significantly lower BDNF levels in PTSD
      patients, as compared with those of healthy subjects (p=0.001), although obtained
      in a small sample size, would suggest that this NT may be involved in the
      pathophysiology of PTSD.

PMID- 19409952
TI  - Overexpression of serine threonine tyrosine kinase 1/novel oncogene with kinase
      domain mRNA in patients with acute leukemia.
AB  - OBJECTIVE: Alterations in gene expression levels or mutations of previously
      reported tyrosine kinases are detected in only limited numbers of patients with
      acute leukemia. In this study, we examined whether serine threonine tyrosine
      kinase 1 (STYK1)/novel oncogene with kinase domain (NOK) is overexpressed in
      patients with acute leukemia. MATERIALS AND METHODS: In peripheral blood cells
      from nonleukemic group and acute leukemic patients, STYK1/NOK messenger RNA
      (mRNA) expression was analyzed by quantitaive reverse transcriptase polymerase
      chain reaction. The effect of inhibition of STYK1/NOK mRNA on the leukemic cells
      was also examined. RESULTS: When appropriate, cutoff was set using the values in
      nonleukemic individuals, positive STYK1/NOK expression was detected in 80.0% of
      leukemic patients. STYK1/NOK mRNA was highly expressed in the patients with
      trisomy/tetrasomy 21. mRNA expression began to decrease after chemotherapy with
      various drugs; this resulted in a decrease in the number of leukemic blasts in
      the patients' peripheral blood samples. Such changes in the gene expression were
      also noted in promyelocytic leukemia (M3) patients treated with all-trans
      retinoic acid. In addition, transfection of small inhibitory RNA against the
      STYK1/NOK gene into K562 cells inhibited their growth in proportion to the
      decrease in the mRNA expression. CONCLUSION: These results indicate that
      STYK1/NOK mRNA is widely expressed in the patients with acute leukemia and
      suggest that inhibition of this molecule could potentially serve as a novel
      therapeutic target.

PMID- 19409953
TI  - Patients with myelodysplastic syndromes display several T-cell expansions, which
      are mostly polyclonal in the CD4(+) subset and oligoclonal in the CD8(+) subset.
AB  - OBJECTIVE: Immune dysregulation plays a role in the pathophysiology of
      myelodysplastic syndromes (MDS), as T-cell clones seem to be involved in the
      inhibition of hematopoietic precursors. The purpose of this study was to analyze
      the T-cell receptor (TCR) repertoire of MDS patients, focusing on the third
      complementarity determining region (CDR3) pattern of their CD4(+) and CD8(+)
      lymphocyte expansions. MATERIALS AND METHODS: The study involved 30 patients and
      15 age-matched controls. The beta-variable (betaV) subfamily flow-cytometry
      analysis was performed on peripheral CD4(+) and CD8(+) T-cells. Spectratyping TCR
      CDR3 analysis was carried out on isolated helper and cytotoxic T lymphocytes
      after immunomagnetic separation and reverse-transcriptase polymerase chain
      reaction. RESULTS: We first identified by flow cytometry an increased frequency
      of expanded betaVs in both CD4(+) and CD8(+) T-cells in MDS patients. We then
      showed, by spectratyping, that the CDR3 profile was mostly Gaussian in their
      CD4(+) T cells, whereas CD8(+) T cells usually showed skewed or oligoclonal CDR3
      regions. When we compared spectratyping and flow-cytometry findings in each
      patient, we showed that most CD4(+) lymphocyte expansions detected by flow
      cytometry had Gaussian CDR3 profiles, whereas most CD8(+) expansions were
      oligoclonal. CONCLUSION: We confirm that in MDS patients the TCR-betaV repertoire
      is overall extremely contracted, especially in cytotoxic T cells. This pattern is
      mainly determined by selective proliferations of both helper and cytotoxic T
      cells, which are, however, mostly polyclonal in the former and oligoclonal in the
      latter. Such a difference, possibly related to the different human leukocyte
      antigen restriction, could reflect the selective involvement of cytotoxic T cells
      either in the anti-tumor immune surveillance or in an autoreactive aggression
      toward hematopoietic precursors.

PMID- 19409954
TI  - Reciprocal expression of Bmi1 and Mel-18 is associated with functioning of
      primitive hematopoietic cells.
AB  - OBJECTIVE: The Polycomb-group (PcG) genes regulate global gene expression in many
      biological processes, including hematopoiesis, by manipulating specific target
      genes. It is known that various PcG genes regulate self-renewal of hematopoietic
      stem cells (HSCs). Here we have shown that the reciprocal expression of PcG
      proteins regulates self-renewal and differentiation of HSCs. METHODS: We used
      murine and human bone marrow cells and evaluated the reciprocal expression of PcG
      proteins on the basis of their respective intranuclear distributions. PcG-gene
      expression in HSCs was knocked down by small interfering RNAs. The function of
      each gene in HSCs was analyzed in vitro and in vivo. RESULTS: Cells were either
      Bmi1-positive or Mel-18-positive. The Bmi1-positive cells contained very little
      amounts of Mel-18 and vice versa. The bmi1-knockdown marrow cells did not show
      HSC function, while the mel-18-knockdown marrow cells showed increased stem cell
      function. Results of the analysis on human cells were similar to those observed
      in case of murine cells. In a clinical investigation, transplantation using
      sources with a low Bmi1 to Mel-18 ratio was associated with early hematopoietic
      recovery. CONCLUSION: Reciprocal expression of Bmi1 and Mel-18 regulated HSC
      function. Here, we observed that expression of the PcG genes-bmi1 and mel-18-is
      correlated with self-renewal and differentiation of HSCs. Thus, it was suggested
      that the balance between Bmi1 and Mel-18 regulates self-renewal of HSCs.

PMID- 19409956
TI  - Memory versus spatial disorder in the support of cooperation.
AB  - In the conventional spatial formulation of the iterated prisoner's dilemma only
      the results generated in the last round are taken into account in deciding the
      next choice. Historic memory can be implemented by featuring players with a
      summary of their previous winnings and moves. The effect of memory as a mechanism
      of supporting cooperation versus spatial disorder is assessed when the players
      are allowed for continuous degree of cooperation, not the mere binary
      cooperation/defection disjunctive.

PMID- 19409955
TI  - Clinical and immunological evaluation of zoledronate-activated Vgamma9gammadelta
      T-cell-based immunotherapy for patients with multiple myeloma.
AB  - OBJECTIVE: To evaluate the potential anti-tumor activity of zoledronate-activated
      Vgamma9gammadelta T cells in vivo, we initiated a pilot study involving
      administration of zoledronate-activated Vgamma9gammadelta T lymphocyte-activated
      killer (LAK) cells to patients with multiple myeloma. MATERIALS AND METHODS:
      Subjects (n = 6) received four intravenous infusions at 2-week intervals of
      zoledronate-activated Vgamma9gammadelta T LAK cells generated from the culture of
      peripheral blood mononuclear cells (PBMCs) in the presence of zoledronate and
      interleukin-2. If the M-protein level in the patient's serum remained at baseline
      following four intravenous infusions, the patient underwent four more treatments
      at 4-week intervals. Subjects (n = 6) received a median of 0.99 x 10(9)
      Vgamma9gammadelta T LAK cells per infusion. RESULTS: No serious treatment-related
      adverse effects were observed during the study period. The percentage of
      Vgamma9gammadelta T cells in PBMCs and absolute numbers of Vgamma9gammadelta T
      cells in peripheral blood, particularly those of CD45RA(-)CD27(-) effector memory
      (TEM) Vgamma9gammadelta T-cell subsets increased in all the patients. Percentages
      of Vgamma9gammadelta T cells and TEM Vgamma9gammadelta T cells in bone marrow
      also increased in all the patients so far tested. M-protein levels in the serum
      remained at baseline in four of six patients and increased in two of six
      patients. Soluble major histocompatibility complex class I chain-related antigen
      A was detected only in the serum of patients whose M-protein level increased.
      CONCLUSION: Administration of zoledronate-activated Vgamma9gammadelta T LAK cells
      is a safe and promising immunotherapy approach for treatment of patients with
      multiple myeloma.

PMID- 19409957
TI  - The melatonin-producing system is fully functional in retinal pigment epithelium
      (ARPE-19).
AB  - Since melatonin production has been documented in extrapineal and extraneuronal
      tissues, we investigated the expression of molecular elements of the
      melatoninergic system in human RPE cells (ARPE-19). The expression of key enzymes
      for melatonin synthesis: tryptophan hydroxylases (TPH1 and TPH2); arylalkylamine
      N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT) was
      detected in ARPE-19 cells using RT-PCR. TPH1 and AANAT proteins were detected in
      ARPE by Western blotting, while sequential metabolism of tryptophan, serotonin
      and N-acetylserotonin to melatonin was shown by RP-HPLC. We also demonstrated, by
      means of RT-PCR, that ARPE expressed mRNA encoding the melatonin receptors: MT2
      (but not MT1), two isoforms of nuclear receptor (RORalpha1 and RORalpha4/RZR1),
      and quinone oxidoreductase (NQO2). By analogy with other peripheral tissues, for
      example the skin, the expression of these metabolic elements in RPE cells
      suggests that the RPE represents an additional source of melatonin in the eye, to
      regulate local homeostasis and prevent from oxidative damage in intra-, auto-
      and/or paracrine fashions.

PMID- 19409958
TI  - Tapping performance and underlying wrist muscle activity of non-drummers,
      drummers, and the world's fastest drummer.
AB  - Studies of rapid unimanual tapping have assumed that the human rate limit for
      voluntary rhythmic movement is 5-7 Hz, which corresponds to an inter-tap interval
      (ITI) of 150-200ms. In fact, the winner of a recent contest to find the world's
      fastest drummer (WFD) can perform such movements using a handheld drumstick at 10
      Hz, which corresponds to an ITI of 100 ms. Because the contest measured only the
      number of taps by the WFD, we examined the stability of the ITI and the
      underlying wrist muscle activity of the WFD. By comparing the performance and
      wrist muscle activity of the WFD with those of two control groups (non-drummers
      (NDs) and ordinary skilled drummers (ODs)), we found that the WFD had a
      relatively stable ITI and more pronounced reciprocal wrist muscle activity during
      the 10-Hz performance. Our result indicates that very fast, stable tapping
      performance can be achieved by keeping the wrist joint compliant rather than
      stiff.

PMID- 19409959
TI  - ACE polymorphism and response to electroconvulsive therapy in major depression.
AB  - The angiotensin I-converting enzyme gene (ACE) has been repeatedly suggested as a
      major gene affecting affective disorders and their treatment, but the study
      results have been ambiguous so far. The primary purpose of this study was to
      compare the effects of the ACE genotype distributions and treatment response to
      electroconvulsive therapy (ECT) in patients with major depressive disorder (MDD).
      The association in ACE genotypes and the age at onset of depression was also
      analyzed and these gene distributions were also compared between patients and
      healthy controls. The study included 119 treatment-resistant MDD patients who
      were referred to ECT treatment, and 392 voluntary blood donors as controls. All
      participants were tested for their ACE genotype, and all study patients were
      evaluated both before and after treatment. The Montgomery-Asberg Depression Scale
      (MADRS) was used as a primary efficacy evaluating method. The ACE genotype was
      not associated in treatment results for MDD. However, younger onset age of
      primary depression was associated with the I/D genotype in the whole patient
      group. The finding was partly gender dependent; in male patients the I allele
      carried a higher risk of earlier depression onset age, while in female patients
      the higher risk was seen only in the heterozygous I/D allele carriers.
      Distributions of these genotypes or alleles did not differ between patients and
      controls. The studied ACE genotype was not associated with ECT results but may be
      associated with age of onset of the illness in patients with MDD.

PMID- 19409960
TI  - Neural bases of behavior selection without an objective correct answer.
AB  - Life choice (e.g. occupation choice) often includes situations with two or more
      possible answers. How does the brain respond to such conflict-ridden situations?
      We investigated whether the dorsal anterior cingulate cortex (dACC) evaluates the
      degree of conflict between possible answers. Additionally, we investigated
      whether the medial prefrontal cortex (MPFC) or the medial temporal lobe (MTL) has
      a function in behavior selection with plural possible answers. We used an
      occupational choice task (e.g. which occupation do you think you could do better?
      dancer or chemist) with two possible answers and a word-length task (e.g. which
      word is longer?-dentist or comedian) that has a correct answer. The conflicts in
      each task were manipulated. Results showed that the dACC and the MTL were
      activated when the conflict during occupational choice was large, and that the
      MPFC and posterior cingulate cortex were activated more in the occupational
      choice task than in the word-length task. Our results show that the dACC
      evaluates the degree of conflict between possible answers, and that the MTL,
      MPFC, and posterior cingulate cortex have a function in behavior selection
      without an objective correct answer. It is thought that the MTL functions to
      reduce conflict when a large-conflict is detected in the dACC. Furthermore, the
      MPFC and posterior cingulate are thought to have a function of biasing any of the
      plural answers in behavior selection without an objective answer.

PMID- 19409961
TI  - Neural basis of attributional style in schizophrenia.
AB  - Attributional style means how people typically infer the causes of emotional
      behaviors. No study has shown neural basis of attributional style in
      schizophrenia, although it was suggested as a major area of social cognition
      research of schizophrenia. Fifteen patients with schizophrenia and 16 healthy
      controls underwent functional magnetic resonance imaging while performing three
      (happy, angry, and neutral) conditions of attribution task. Each condition
      included inferring situational causes of an avatar' (virtual character) emotional
      or neutral behavior. In the between-groups contrast maps of the happy conditions,
      the patient group compared to the control group showed decreased activations in
      the inferior frontal (BA 44) and the ventral premotor cortex (BA 6), in which the
      % signal changes were associated with negative symptoms. In the angry conditions,
      the patient group compared to the control group exhibited increased activations
      in the precuneus/posterior cingulate cortex (Pcu/PCC) (BA 7/31), in which the %
      signal changes were related to positive symptoms. In conclusion, patients with
      schizophrenia may have functional deficits in mirror neuron system when
      attributing positive behaviors, which may be related to a lack of inner
      simulation and empathy and negative symptoms. In contrast, patients may have
      increased activation in the Pcu/PCC related to self-representations while
      attributing negative behaviors, which may be related to failures in self- and
      source-monitoring and positive symptoms.

PMID- 19409962
TI  - Identification of the medial lemniscus in the human brain: combined study of
      functional MRI and diffusion tensor tractography.
AB  - The medial lemniscus (ML) plays a critical role in sensory function and skillful
      movement. Using combined functional MRI (fMRI) and diffusion tensor tractography
      (DTT), we attempted to identify the ML pathway and quantify the characteristics
      of the ML compared to the corticospinal tract (CST). Eleven young healthy
      subjects without any history of neurological disorder were recruited for this
      study. For tracking of the ML, a seed region of interest (ROI) was determined
      using the fMRI activation in the primary sensorimotor cortex (SM1) following
      proprioceptive input, and a target ROI was given in the ML area of the pons. We
      were able to locate the ML in 9 out of 11 subjects. All ML started from the ML
      area just posterior to the transpontine fiber in the pons, and ascended to the
      SM1 posterolaterally to the cerebral peduncle of the midbrain, the posterior limb
      of the internal capsule (PLIC), and the corona radiata along with the CST. The
      fractional anisotropy (FA) value of the ML was similar to that of the CST. We
      could identify the ML pathway in the human brain using the combined fMRI/DTT
      method. These results and technique will be helpful for research about the ML in
      the human brain.

PMID- 19409965
TI  - Mitochondrial DNA mutations and ageing.
AB  - The mechanism by which we age has sparked a huge number of theories, and is an
      area of intense debate. As the elderly population rises, the importance of
      elucidating these mechanisms is becoming more apparent as age is the single
      biggest risk factor for a number of diseases such as cancer, diabetes and
      neurodegenerative disease. Mitochondrial DNA (MtDNA) mutations have been shown to
      accumulate in cells and tissues during the ageing process; however the question
      as to whether these mutations have a causal role in the ageing process remains an
      area of uncertainty. Here we review the current literature, and discuss the
      evidence for and against a causal role of mtDNA mutations in ageing and in the
      pathogenesis of age-related disease.

PMID- 19409964
TI  - New extension of the Mitchell Theory for oxidative phosphorylation in
      mitochondria of living organisms.
AB  - The Mitchell Theory implies the proton motive force Deltap across the inner
      mitochondrial membrane as the energy-rich intermediate of oxidative
      phosphorylation. Deltap is composed mainly of an electrical (DeltaPsi(m)) and a
      chemical part (DeltapH) and generated by the respiratory chain complexes I, III
      and IV. It is consumed mostly by the ATP synthase (complex V) to produce ATP. The
      free energy of electron transport within the proton pumps is sufficient to
      generate Deltap of about 240 mV. The proton permeability of biological membranes,
      however, increases exponentially above 130 mV leading to a waste of energy at
      high values (DeltaPsi(m)>140 mV). In addition, at DeltaPsi(m)>140 mV, the
      production of the superoxide radical anion O(2)(-) at complexes I, II and III
      increases exponentially with increasing DeltaPsi(m). O(2)(-) and its neutral
      product H(2)O(2) (=ROS, reactive oxygen species) induce oxidative stress which
      participates in aging and in the generation of degenerative diseases. Here we
      describe a new mechanism which acts independently of the Mitchell Theory and
      keeps DeltaPsi(m) at low values through feedback inhibition of complex IV
      (cytochrome c oxidase) at high ATP/ADP ratios, thus preventing the formation of
      ROS and maintaining high efficiency of oxidative phosphorylation.

PMID- 19409963
TI  - A role for a novel protein, nucleolin, in Parkinson's disease.
AB  - Although much has been learned in the last few decades concerning the molecular
      mechanisms and pathways associated with the development of familial as well as
      sporadic Parkinson disease (PD), the precise mechanisms and specific proteins
      responsible for mediating these effects remain to be elucidated. Thus, the
      identification and biological evaluation of novel proteins involved in these
      pathways is critical to providing a more comprehensive understanding of PD
      pathogenesis. Previously, in a cellular model of PD, we identified nucleolin as a
      protein interacting with alpha-synuclein and DJ-1, two critical proteins involved
      in PD pathogenesis. In our current study, we found the expression levels of
      nucleolin were dramatically reduced in the substantia nigra pars compacta of
      human PD subjects, compared with controls. Furthermore, manipulation of nucleolin
      in an in vitro model of PD resulted in significant alterations in the generation
      of oxidative stress as well as proteasomal inhibition following rotenone
      exposure. Interestingly, nucleolin expression did not influence mitochondrial
      complex I activity, suggesting a selective specificity for oxidative stress and
      proteasomal pathways.

PMID- 19409966
TI  - Effects of estrogens and progesterone on the synaptic organization of the
      hypothalamic ventromedial nucleus.
AB  - The majority of the studies on the actions of estrogens in the ventrolateral part
      of the hypothalamic ventromedial nucleus (VMNvl) concern the factors that
      modulate the receptive component of the feminine sexual behavior and the
      expression of molecular markers of neuronal activation. To further our
      understanding of the factors that regulate synaptic plasticity in the female
      VMNvl, we have examined the effects of estradiol and progesterone, and of
      estrogen receptor (ER) subtype selective ligands on the number of dendritic and
      spine synapses established by individual VMNvl neurons and on sexual behavior. In
      contrast to earlier studies that analyzed synapse densities, our results show
      that exogenous estradiol increases the number of spine as well as of dendritic
      synapses, irrespective of the dose and regimen of administration. They also
      reveal that an effective dose of estradiol administered as one single pulse
      induces the formation of more synapses than the same dose administered as two
      pulses on consecutive days. Our results further show that both ER subtypes are
      involved in the mediation of the synaptogenic effects of estrogens on VMNvl
      neurons since the administration of the selective ERalpha, propyl-pyrazole-triol
      (PPT), and ERbeta, diarylpropionitrile (DPN), agonists induced a significant
      increase in the number of synapses that, however, was more exuberant for PPT.
      Despite its relevant role in feminine sexual behavior, progesterone had no
      synaptogenic effect in the VMNvl as no changes in synapse numbers were noticed in
      rats treated with progesterone alone, with estradiol followed by progesterone or
      with the antiprogestin mifepristone (RU486). Except for the sequential
      administration of estradiol and progesterone, none of the regimens was associated
      with lordosis response to vaginocervical stimulation. Therefore, from the sex
      steroids that undergo cyclic variations over the estrous cycle, only estrogens,
      acting through both ERalpha and ERbeta, play a key role in the activation of the
      neural circuits involving the ventromedial nucleus of the hypothalamus.

PMID- 19409967
TI  - Edaravone attenuates white matter lesions through endothelial protection in a rat
      chronic hypoperfusion model.
AB  - A multicenter randomized clinical trial demonstrated that acute ischemic stroke
      patients treated with edaravone, a scavenger of hydroxyl radicals, had
      significant functional improvement. We tested the hypothesis that edaravone has
      protective effects against white matter lesions (WML) and endothelial injury,
      using a rat chronic hypoperfusion model. Adult Wistar rats underwent ligation of
      bilateral common carotid artery (LBCCA) and were divided into the edaravone group
      (injected once only immediately after LBCCA [n=39, ED(1)]; and injected on three
      consecutive days [n=39, ED(3)]), the vehicle group (n=39), and the sham group
      (n=15). Cerebral blood flow, Morris water maze performance, footprint test for
      locomotor function, immunohistochemical analyses and Western blot analysis were
      performed before and after LBCCA. The ED(3) group upregulated endothelial nitric
      oxide synthase and attenuated Evans Blue extravasation at day 3 after LBCCA
      (P<0.05). Edaravone markedly suppressed accumulation of 4-hydroxy-2-nonenal
      modified protein and 8-hydroxy-deoxyguanosine (P<0.01), and loss of
      oligodendrocytes (P<0.05) in the cerebral white matter at days 3, 7, 14, 21 and
      28 after LBCCA. These results were more evident in the ED(3) group. Moreover, at
      day 21 after LBCCA, spatial memory but not motor function, and axonal damage were
      significantly improved by three-time treatment of edaravone (P<0.05). Our results
      indicated that 3-day treatment with edaravone provides protection against WML
      through endothelial protection and free radical scavenging and suggested that
      edaravone is potentially useful for the treatment of cognitive impairment.

PMID- 19409968
TI  - Inflammation-induced increase in hyperpolarization-activated, cyclic nucleotide
      gated channel protein in trigeminal ganglion neurons and the effect of
      buprenorphine.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are active at
      resting membrane potential and thus contribute to neuronal excitability. Their
      increased activity has recently been demonstrated in models of nerve injury
      induced pain. The major aim of the current study was to investigate altered HCN
      channel protein expression in trigeminal sensory neurons following inflammation
      of the dura. HCN1 and HCN2 channel immunoreactivity was observed on the membranes
      of medium- to large-sized trigeminal ganglion neurons with 76% and 85% of HCN1
      and HCN2 expressing neurons also containing the 200 kDa neurofilament protein
      (associated with myelinated fibers). Western immunoblots of lysates from rat
      trigeminal ganglia also showed bands with appropriate molecular weights for HCN1
      and HCN2. Three days after application of complete Freund's adjuvant (CFA) to the
      dura mater, Western blot band densities were significantly increased; compared to
      control, to 166% for HCN1 and 284% for HCN2 channel protein. The band densities
      were normalized against alpha-actin. In addition, the number of retrogradely
      labeled neurons from the dura expressing HCN1 and HCN2 was significantly
      increased to 247% (HCN1) and 171% (HCN2), three days after inflammation. When the
      opioid receptor partial agonist, buprenorphine, was given systemically,
      immediately after CFA, the inflammation-induced increase in HCN protein
      expression in both Western blot and immunohistochemical experiments was not
      observed. These results suggest that HCN1 and HCN2 are involved in inflammation
      induced sensory neuron hyperexcitability, and indicate that an opioid receptor
      agonist can reverse the protein upregulation.

PMID- 19409969
TI  - Effects of hearing aid fitting on the perceptual characteristics of tinnitus.
AB  - Restoration of auditory input through the use of hearing aids has been proposed
      as a potentially important means of altering tinnitus among those tinnitus
      sufferers who experience significant sensorineural hearing loss. In animal models
      of neural plasticity induced by noise trauma, high-frequency stimulation in
      deafferented regions of the auditory spectrum has been shown to modulate cortical
      reorganization after hearing loss, a result which suggests that the neural basis
      of tinnitus is subject to interference by acoustic stimulation. This study drew
      on deafferentation models to investigate the effect of hearing aids on the
      psychoacoustic properties of the tinnitus sensation, using both conventional
      amplification and high-bandwidth amplification regimes. The tinnitus percept was
      affected only weakly in the conventional amplification group, and was not at all
      affected in the high-bandwidth group. The changes observed under conventional,
      low-to-medium frequency amplification may indicate that the perceptual
      characteristics of tinnitus depend on the pattern of sensory inputs - notably a
      contrast in activity between adjacent central auditory regions of more and less
      afferent activity - while the absence of modifications in the high-bandwidth
      amplification group suggests limit on the tractability of the tinnitus percept.
      This limit to the malleability of the tinnitus percept may arise from either the
      extent of hearing deficits or the duration and robustness of the neuroplastic
      changes that originally give rise to tinnitus.

PMID- 19409970
TI  - Antiviral effect of Curcuma longa Linn extract against hepatitis B virus
      replication.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A medicinal herb Curcuma longa Linn has been used
      for treating various liver diseases caused by hepatitis B virus (HBV) in Asia.
      AIM OF THE STUDY: The study was performed in order to investigate the antiviral
      activity of Curcuma longa Linn against HBV replication in liver cells. MATERIALS
      AND METHODS: Aqueous extract of Curcuma longa Linn (CLL) was prepared and used to
      analyze its antiviral activity against HBV replication in HepG 2.2.15 cells,
      which contain HBV genomes. The inhibitory effect of CLL on HBV replication was
      examined by testing the levels of secreted HBV surface antigens (HBsAg), HBV
      DNAs, and HBV RNAs in HepG 2.2.15 cells using ELISA, Southern blot, and Northern
      blot analyses. Cytotoxic activities of CLL extract on various liver cells were
      analyzed by MTT assay. To dissect the inhibitory mechanism of CLL extract on HBV
      replication, the levels of p53 protein and p53 mRNAs were analyzed by Western
      blot and RT-PCR in HepG 2.2.15 cells. The repression of CLL extract on HBV
      transcription was analyzed by RT-PCR and CAT assay. RESULTS: CLL extract
      repressed the secretion of HBsAg from HepG 2.2.15 cells. CLL extract also
      suppressed the production of HBV particles and the level of intracellular HBV
      RNAs in HepG 2.2.15 cells, suggesting that CLL extract inhibits HBV replication.
      We found that the anti-HBV activity of CLL extract is mediated through enhancing
      the cellular accumulation of p53 protein by transactivating the transcription of
      p53 gene as well as increasing the stability of p53 protein. It turned out that
      CLL extract repressed the transcription of HBx gene by suppressing HBV enhancer I
      and X promoter through p53 protein. In addition, CLL extract did not have any
      cytotoxic effects on liver cells. CONCLUSION: These data showed that CLL extract
      represses HBV replication through enhancing the level of p53 protein. CLL extract
      can be used as a safe and specific drug for patients with liver diseases caused
      by HBV infection.

PMID- 19409971
TI  - Neuroprotective effect of Buyang Huanwu Decoction on spinal ischemia/reperfusion
      injury in rats.
AB  - AIM OF THE STUDY: The aim of this study was to investigate the protective effect
      of Buyang Huanwu Decoction, a traditional Chinese medicine formula, on spinal
      ischemia/reperfusion injury and explore the possible mechanism of the protective
      effect. MATERIALS AND METHODS: The spinal ischemia/reperfusion injury model was
      conducted in male Sprague-Dawley rats, and 40 g/kg Buyang Huanwu Decoction was
      administered by introgastric infusion. Motor function of hind limbs and apoptosis
      index were measured 72 h after reperfusion was started. The expression of
      thioredoxin and thioredoxin reductase was examined at 6h and at 24h after
      reperfusion. RESULTS: Motor function scores and apoptosis indices were
      significantly improved in the Buyang Huanwu Decoction group, as compared to the
      saline-infused control group. Spinal ischemia/reperfusion injury resulted in a
      decrease in the expression of thioredoxin, while Buyang Huanwu Decoction
      administration greatly elevated the expression of thioredoxin-1/thioredoxin-2
      mRNA and thioredoxin reductase-1/thioredoxin reductase-2 mRNA. CONCLUSIONS: Our
      results suggest that administration of Buyang Huanwu Decoction may reduce spinal
      ischemia/reperfusion damage. This neuroprotective effect may be mediated, in
      part, by an increase in the transcription of thioredoxin.

PMID- 19409972
TI  - Age-dependent increases in interstitial collagenase and MAP Kinase levels are
      exacerbated by superoxide dismutase deficiencies.
AB  - Many age-associated degenerative diseases commonly involve degradation of the
      extracellular matrix and aberrant matrix metalloproteinase-1 (MMP-1) expression.
      In diverse cell lines MMP-1 or interstitial collagenase (CL) expression is
      tightly regulated through a network of signals involving reactive oxygen species
      (ROS). However, whether the in vivo age-associated increase in CL expression is
      also sensitive to ROS-mediated signaling has not been established. To evaluate
      the contribution of ROS to the age-dependent increase in CL we monitored the
      levels of murine CL in two well-established models of oxidant stress. Analysis of
      murine CL levels in mice deficient in either of the intracellular superoxide
      dismutases (Sod2(+/-) or Sod1(-/-)) revealed its age- and redox-dependent
      expression relative to WT controls. Both age- and redox-dependent increases in
      murine CL expression were associated with elevations in phosphorylation of the
      MAP Kinases, Erk, JNK and p38. CL expression was highest in renal and skeletal
      muscle tissue from the aged Sod1(-/-) mice and was associated with a decrease in
      collagen staining. These findings suggest that MAPK signaling and CL production
      are both age- and redox-responsive. The redox sensitivity of age-associated CL
      expression suggests that degenerative disease associated with aberrant matrix
      remodeling and oxidant stress may be amenable to antioxidant-based therapies.

PMID- 19409974
TI  - The encapsulation technology in fruit plants--a review.
AB  - Encapsulation technology is an exciting and rapidly growing area of
      biotechnological research. This has drawn tremendous attention in recent years
      because of its wide use in conservation and delivery of tissue cultured plants of
      commercial and economic importance. Production of synthetic seeds by
      encapsulating somatic embryos, shoot buds or any other meristmatic tissue helps
      in minimizing the cost of micropropagated plantlets for commercialization and
      final delivery. In most of fruit crops, seed propagation has not been successful
      because of heterozygosity of seeds, minute seed size, presence of reduced
      endosperm, low germination rate, and also some are having seedless varieties.
      Many species have desiccation-sensitive intermediate or recalcitrant seeds and
      can be stored for only a few weeks or months. Under these circumstances,
      increasing interest has been shown recently to use encapsulation technology for
      propagation and conservation. Many fruit plants are studied worldwide for
      breeding, genetic engineering, propagation, and pharmaceutical purposes. In this
      context, synthetic seeds would be more applicable in exchange of elite and axenic
      plant material between laboratories and extension centers due to small bead size
      and ease in handling. Due to these advantages, interest in using encapsulation
      technology has continuously been increasing in several fruit plant species. The
      purpose of this review is to focus upon current information on development of
      synthetic seeds in several fruit crops.

PMID- 19409973
TI  - A new Schizosaccharomyces pombe chronological lifespan assay reveals that caloric
      restriction promotes efficient cell cycle exit and extends longevity.
AB  - We describe a new chronological lifespan (CLS) assay for the yeast
      Schizosaccharomyces pombe. Yeast CLS assays monitor the loss of cell viability in
      a culture over time, and this new assay shows a continuous decline in viability
      without detectable regrowth until all cells in the culture are dead. Thus, the
      survival curve is not altered by the generation of mutants that can grow during
      the experiments, and one can monitor the entire lifespan of a strain until the
      number of viable cells has decreased over 10(6)-fold. This CLS assay
      recapitulates the evolutionarily conserved features of lifespan shortening by
      over nutrition, lifespan extension by caloric restriction, increased stress
      resistance of calorically restricted cells and lifespan control by the AKT
      kinases. Both S. pombe AKT kinase orthologs regulate CLS: loss of sck1(+)
      extended lifespan in over nutrition conditions, loss of sck2(+) extended lifespan
      under both normal and over nutrition conditions, and loss of both genes showed
      that sck1(+) and sck2(+) control different longevity pathways. The longest-lived
      S. pombe cells showed the most efficient cell cycle exit, demonstrating that
      caloric restriction links these two processes. This new S. pombe CLS assay will
      provide a valuable tool for aging research.

PMID- 19409976
TI  - Detection of TT virus in HIV-1 exposed but uninfected individuals and in HIV-1
      infected patients and its influence on CD4+ lymphocytes and viral load.
AB  - The TT virus (TTV) was detected for the first time in the serum of a patient with
      post-transfusion hepatitis of unknown origin. TTV was subsequently, also found in
      the serum of blood donors with no history of blood transfusion. In the present
      study, the percentage of TTV carriers among HIV-infected and noninfected patients
      was determined. The study was conducted to evaluate CD4 count and HIV viral load
      in 100 asymptomatic patients infected with HIV-1, 100 symptomatic patients with
      AIDS, 100 HIV-1 exposed but uninfected individuals and 100 normal healthy blood
      donors. In this work, the presence of TTV was investigated by nested-PCR. TTV was
      detected in 6% of normal donors, 12.5% of HIV-infected individuals and 21% of
      exposed individuals. The presence of TTV was statistically significant in the HIV
      exposed individuals (21/100) compared with blood donors (6/100). Odds ratio=4.16
      (95%CI 1.60-10.83). No inter-group relations were found for CD4 and CD8 counts or
      HIV viral load. In the symptomatic group, patients with TTV presented minor viral
      load. This work demonstrated that TTV was detected in HIV-exposed individuals and
      no relation was verified for CD4, CD8 and viral load in the asymptomatic and
      symptomatic HIV patients.

PMID- 19409975
TI  - Recombinant interleukin-4 enhances Campylobacter jejuni invasion of intestinal
      pig epithelial cells (IPEC-1).
AB  - Campylobacter jejuni, a leading cause of bacterial gastroenteritis, has a diverse
      spectrum of disease expression. Polymicrobial infections may contribute to this,
      such as Trichuris, which elicits type 2 cytokines (including IL-4) and
      downregulates type 1 immunity. In previous studies, gnotobiotic piglets infected
      with C. jejuni and Trichuris suis had bloody diarrhea and marked gastrointestinal
      pathology, including bacterial invasion into epithelial cells and macrophages.
      Neonatal swine given these dual infections had elevated IL-4 and IL-10 responses
      in feces. In the studies reported here, we hypothesized that IL-4 or IL-10
      enhances invasion of intestinal pig epithelial cells (IPEC-1) by C. jejuni. 10-14
      day-old IPEC-1 cells were pretreated with recombinant IL-4 (rIL-4) or rIL-10 for
      5h and then challenged with C. jejuni. Cells pretreated with rIL-4 were viable
      and showed approximately 6-fold increases in C. jejuni (but not Escherichia coli
      DH5alpha) internalization compared to cells with no pretreatment. Enhanced C.
      jejuni invasion was rIL-4 dose-dependent and reversed by addition of anti-IL-4
      antibody. Preincubation with rIL-10 did not significantly alter C. jejuni
      internalization. Transepithelial electrical resistance (TEER) was significantly
      reduced following rIL-4 treatment, but not rIL-10 treatment. After rIL-4
      pretreatment and C. jejuni challenge, light microscopy showed vacuolated cells
      with damaged paracellular junctions. Transmission electron microscopy (TEM)
      showed multiple internalized bacteria. Most were in the cytoplasm, but some were
      within or adjacent to vacuoles. We conclude that rIL-4 damages paracellular
      junctions and alters the physiology of these epithelial cells allowing increased
      invasion of C. jejuni.

PMID- 19409977
TI  - Does the nature of neonatal host anti-viral immunity control adult brain
      function?

PMID- 19409978
TI  - Expression patterns of 5-HT receptor subtypes 1A and 2A on GABAergic neurons
      within the spinal dorsal horn of GAD67-GFP knock-in mice.
AB  - 5-HT plays an important role in GABA transmission at the spinal cord level. The
      main purpose of the present article is to find out, which 5-HT receptor subtypes
      may be involved in the regulation of GABAergic transmission in the spinal dorsal
      horn, by using the combination of tissue RT-PCR, single-cell RT-PCR and double
      immunofluorescent staining on the GAD(67)-GFP knock-in mice. The present result
      showed that 5-HT(1A) receptor subtype mRNA was present on about half of GFP
      positive GABAergic interneurons in the spinal dorsal horn, which suggests a role
      of 5-HT(1A) receptor in GABA-mediated modulation of nociception at the spinal
      cord level. However, it is unexpected that just a very limited sub-population of
      the total GABAergic interneurons express 5-HT(2A) receptor mRNA or proteins in
      the spinal dorsal horn, which suggests that the 5-HT(2A) receptor subtype may not
      be important for spinal GABAergic effects in nociceptive modulation.

PMID- 19409980
TI  - A novel role for vitamin B(12): Cobalamins are intracellular antioxidants in
      vitro.
AB  - Oxidative stress is a feature of many chronic inflammatory diseases. Such
      diseases are associated with up-regulation of a vitamin B(12) (cobalamin) blood
      transport protein and its membrane receptor, suggesting a link between cobalamin
      and the cellular response to inflammation. The ability of cobalamin to regulate
      inflammatory cytokines suggests that it may have antioxidative properties. Here
      we show that cobalamins, including the novel thiolatocobalamins N-acetyl-l
      cysteinylcobalamin and glutathionylcobalamin, are remarkably effective
      antioxidants in vitro. We also show that thiolatocobalamins have superior
      efficacy compared with other cobalamin forms, other cobalamins in combination
      with N-acetyl-l-cysteine (NAC) or glutathione (GSH), and NAC or GSH alone.
      Pretreatment of Sk-Hep-1 cells with thiolatocobalamins afforded robust protection
      (>90% cell survival) against exposure to 30 microM concentrations of the pro
      oxidants homocysteine and hydrogen peroxide. The compounds inhibited
      intracellular peroxide production, maintained intracellular glutathione levels,
      and prevented apoptotic and necrotic cell death. Moreover, thiolatocobalamins are
      remarkably nontoxic in vitro at supraphysiological concentrations (>2 mM). Our
      results demonstrate that thiolatocobalamins act as powerful but benign
      antioxidants at pharmacological concentrations. Because inflammatory oxidative
      stress is a component of many conditions, including atherosclerosis, dementia,
      and trauma, their utility in treating such disorders merits further
      investigation.

PMID- 19409979
TI  - Differential gene expression in young and senescent endothelial cells under
      static and laminar shear stress conditions.
AB  - Laminar shear stress (LSS) caused by blood flow is known to regulate endothelial
      function and to contribute to vascular health. By way of contrast, endothelial
      cell senescence seems to increase the incidence of vascular disorders. In an
      attempt to identify genes associated with vascular health/disease states, this
      study assessed the differential gene expression of young and senescent human
      umbilical vein endothelial cells (HUVECs) under static and LSS conditions.
      Replicative cell senescence was induced by continuous subculture in vitro, and
      LSS was provided using a cone-and-plate device. Young (p4) and senescent (p18)
      cells were subjected to LSS at 12 dyn.cm(-2) or maintained under static
      conditions for 24 h. Total mRNA was subjected to cDNA microarray analysis using
      the Affymetrix GeneChip. Welch t test at a significance level of p < 0.05
      provided 961 "LSS-responsive" genes, whose expression was altered by LSS in both
      young and senescent cells, and 529 "senescence-responsive" genes differentially
      expressed in young vs senescent cells under both static and LSS conditions. The
      LSS-responsive and senescence-responsive gene groups included 74 genes held in
      common; these may prove useful for the study of cellular responses commonly
      affected by LSS and senescence. Among them, 20 genes whose expression was
      increased by LSS and simultaneously decreased by cellular senescence are
      suggested as potential vascular health markers in the sense that LSS is
      antiatherogenic, whereas senescence is proatherogenic. These genes included
      argininosuccinate synthetase 1, which was determined to be critical for both
      basal and LSS-induced NO production in young HUVECs. Furthermore, its diminished
      expression, and not that of nitric oxide synthase 3, was implicated in the
      insufficient NO production exhibited by senescent HUVECs under LSS conditions.
      The genes identified in this study are expected to facilitate improvements in our
      current level of understanding regarding endothelial physiology in association
      with age-associated vascular disease.

PMID- 19409981
TI  - Real-time imaging of novel spatial and temporal responses to photodynamic stress.
AB  - Cells subjected to various forms of stress have been shown to induce bystander
      responses in nontargeted cells, thus extending the stress response to a larger
      population. However, the mechanism(s) of bystander responses remains to be
      clearly identified, particularly for photodynamic stress. Oxidative stress and
      cell viability were studied on the spatial and temporal levels after photodynamic
      targeting of a subpopulation of EMT6 murine mammary cancer cells in a multiwell
      plate by computerized time-lapse fluorescence microscopy. In the targeted
      population a dose-dependent loss of cell viability was observed in accordance
      with increased oxidative stress. This was accompanied by increased oxidative
      stress in bystander populations but on different time scales, reaching a maximum
      more rapidly in targeted cells. Treatment with extracellular catalase, or the
      NADPH oxidase inhibitor diphenyleneiodinium, decreased production of reactive
      oxygen species (ROS) in both populations. These effects are ascribed to
      photodynamic activation of NADPH-oxidase in the targeted cells, resulting in a
      rapid burst of ROS formation with hydrogen peroxide acting as the signaling
      molecule responsible for initiation of these photodynamic bystander responses.
      The consequences of increased oxidative stress in bystander cells should be
      considered in the overall framework of photodynamic stress.

PMID- 19409982
TI  - Metabolic syndrome and oxidative stress.
AB  - Metabolic syndrome is an obesity-associated collection of disorders, each of
      which contributes to cardiovascular risk. Metabolic syndrome is also associated
      with overproduction of reactive oxygen species (ROS). ROS contribute to the
      interrelationship between metabolic syndrome and salt-sensitive hypertension,
      which are both caused by obesity and excess salt consumption and are major
      threats to health in developed countries. ROS can induce insulin resistance,
      which is indispensable for the progression of metabolic syndrome, and salt
      sensitive hypertension stimulates ROS production, thereby promoting the
      development of metabolic syndrome. Moreover, ROS activate mineralocorticoid
      receptors (MRs) and the sympathetic nervous system, which can contribute to the
      development of metabolic syndrome and salt-sensitive hypertension. Salt-induced
      progression of cardiovascular disease (CVD) is also accelerated in animal models
      with metabolic syndrome, probably owing to further stimulation of ROS
      overproduction and subsequent ROS-induced MR activation and sympathetic
      excitation. Therefore, ROS contribute to the progression of the metabolic
      syndrome itself and to the CVD accompanying it, particularly in conjunction with
      excessive salt consumption.

PMID- 19409983
TI  - Manumycin inhibits STAT3, telomerase activity, and growth of glioma cells by
      elevating intracellular reactive oxygen species generation.
AB  - The poor prognosis of glioblastoma multiforme and lack of effective therapy have
      necessitated the identification of new treatment strategies. We have previously
      reported that elevation of oxidative stress induces apoptosis of glioma cells.
      Because the farnesyltransferase inhibitor manumycin is known to induce reactive
      oxygen species (ROS) generation, we evaluated the effects of manumycin on glioma
      cells. Manumycin induced glioma cell apoptosis by elevating ROS generation.
      Treatment with the ROS inhibitor N-acetylcysteine blocked manumycin-induced
      apoptosis, caspase-3 activity, and PARP expression, indicating the involvement of
      increased ROS in the proapoptotic activity of manumycin. This heightened ROS
      level was accompanied by a concurrent decrease in antioxidants such as superoxide
      dismutase (SOD-1) and thioredoxin (TRX-1). SOD-1 overexpression protects glioma
      cells from manumycin-induced apoptosis. In addition, small interfering RNA
      mediated knockdown of SOD-1 and TRX-1 expression also increased ROS generation
      and sensitivity of glioma cells to manumycin-induced cell death. Interestingly,
      suppressing ROS generation prevented manumycin-induced Ras inhibition. This study
      reports for the first time that Ras inhibition by manumycin is due to heightened
      ROS levels. We also report for the first time that manumycin inhibits the
      phosphorylation of signal transducer and activator of transcription 3 and
      telomerase activity in a ROS-dependent manner, which plays a crucial role in
      glioma resistance to apoptosis. In addition manumycin (i) induced the DNA-damage
      repair response, (ii) affected cell-cycle-regulatory molecules, and (iii)
      impaired the colony-forming ability of glioma cells in a ROS-dependent manner.

PMID- 19409984
TI  - Context-specific requirements of functional domains of the Spectraplakin Short
      stop in vivo.
AB  - Spectraplakins are large multifunctional cytoskeletal interacting molecules
      implicated in various processes, including gastrulation, wound healing, skin
      blistering and neuronal degeneration. It has been speculated that the various
      functional domains and regions found in Spectraplakins are used in context
      specific manners, a model which would provide a crucial explanation for the
      multifunctional nature of Spectraplakins. Here we tested this possibility by
      studying domain requirements of the Drosophila Spectraplakin Short stop (Shot) in
      three different cellular contexts in vivo: (1) neuronal growth, which requires
      dynamic actin-microtubule interaction; (2) formation and maintenance of tendon
      cells, which depends on highly stabilised arrays of actin filaments and
      microtubules, and (3) compartmentalisation in neurons, which is likely to involve
      cortical F-actin networks. Using these cellular contexts for rescue experiments
      with Shot deletion constructs in shot mutant background, a number of differential
      domain requirements were uncovered. First, binding of Shot to F-actin through the
      first Calponin domain is essential in neuronal contexts but dispensable in tendon
      cells. This finding is supported by our analyses of shot(kakP2) mutant embryos,
      which produce only endogenous isoforms lacking the first Calponin domain. Thus,
      our data demonstrate a functional relevance for these isoforms in vivo. Second,
      we provide the first functional role for the Plakin domain of Shot, which has a
      strong requirement for compartmentalisation in neurons and axonal growth,
      demonstrating that Plakin domains of long Spectraplakin isoforms are of
      functional relevance. Like the Calponin domain, also the Plakin domain is
      dispensable in tendon cells, and the currently assumed role of Shot as a linker
      of microtubules to the tendon cell surface may have to be reconsidered. Third, we
      demonstrate a function of Shot as an actin-microtubule linker in dendritic
      growth, thus shedding new light into principal growth mechanisms of this neurite
      type. Taken together, our data clearly support the view that Spectraplakins
      function in tissue-specific modes in vivo, and even domains believed to be
      crucial for Spectraplakin function can be dispensable in specific contexts.

PMID- 19409985
TI  - Predicting the diffusion coefficient of water vapor through glassy HPMC films at
      different environmental conditions using the free volume additivity approach.
AB  - Prediction of diffusion coefficient of polymer materials is important in the
      pharmaceutical research and becomes the aim of this paper. This paper bases the
      prediction method on the estimation of the polymer fractional free volume at
      different environmental conditions. Focussing on glassy polymers, the free
      volumes of polymer films were estimated using the model of Vrentas et al. [J.S.
      Vrentas, J.L. Duda, H.-C. Ling, Antiplasticization and volumetric behavior in
      glassy polymers, Macromolecules 21 (1988) 1470-1475]. The required data are the
      moisture sorption and glass transition temperature data, which were measured on
      various hydroxypropyl methylcellulose (used as a model material) free films at
      different water activities. The temperature and molecular weight particularly
      determine the free volume of the polymer, while the sorbed water can either
      decrease or increase the specific free volume of the polymer. At high water
      activity, the amount of water sorbed in the film increases to such level that the
      direct free volume addition by water becomes proportional to the contribution of
      the polymer itself. This confirms the importance of considering the environmental
      effect on the diffusivity of polymer during coating material selection. The
      presented approach enables the prediction of the diffusivity at any given
      relevant material variable and therefore has the potency to be used as a
      formulation development tool.

PMID- 19409986
TI  - Acute hepatitis C virus infection in an HIV clinic and in community settings.

PMID- 19409987
TI  - Acute hepatitis C.

PMID- 19409989
TI  - Targeting nanoparticles to M cells with non-peptidic ligands for oral
      vaccination.
AB  - The presence of RGD on nanoparticles allows the targeting of beta1 integrins at
      the apical surface of human M cells and the enhancement of an immune response
      after oral immunization. To check the hypothesis that non-peptidic ligands
      targeting intestinal M cells or APCs would be more efficient for oral
      immunization than RGD, novel non-peptidic and peptidic analogs (RGD
      peptidomimitic (RGDp), LDV derivative (LDVd) and LDV peptidomimetic (LDVp)) as
      well as mannose were grafted on the PEG chain of PCL-PEG and incorporated in PLGA
      based nanoparticles. RGD and RGDp significantly increased the transport of
      nanoparticles across an in vitro model of human M cells as compared to
      enterocytes. RGD, LDVp, LDVd and mannose enhanced nanoparticle uptake by
      macrophages in vitro. The intraduodenal immunization with RGDp-, LDVd- or mannose
      labeled nanoparticles elicited a higher production of IgG antibodies than the
      intramuscular injection of free ovalbumin or intraduodenal administration of
      either non-targeted or RGD-nanoparticles. Targeted formulations were also able to
      induce a cellular immune response. In conclusion, the in vitro transport of
      nanoparticles, uptake by macrophages and the immune response were positively
      influenced by the presence of ligands at the surface of nanoparticles. These
      targeted-nanoparticles could thus represent a promising delivery system for oral
      immunization.

PMID- 19409990
TI  - In vivo and in vitro anti-cancer activity of thermo-sensitive and photo
      crosslinkable doxorubicin hydrogels composed of chitosan-doxorubicin conjugates.
AB  - Doxorubicin was chemically conjugated to acrylated chitosan in order to obtain
      sustained-release profiles of doxorubicin from thermo-responsive and photo
      crosslinkable hydrogels. Chitooligosaccharide was acrylated with glycidyl
      methacrylate and subsequently conjugated to doxorubicin via an amide linkage. A
      mixture of doxorubicin-chitosan conjugates, acrylated Pluronic, and doxorubicin
      formed physical gels at 37 degrees C. Photo-irradiation was subsequently
      performed to chemically crosslink the physical hydrogel at 37 degrees C.
      Chitooligosaccharide-doxorubicin conjugates in the doxorubicin hydrogels
      significantly reduced burst release of free doxorubicin from doxorubicin
      hydrogels compared hydrogels without the conjugates. Upon incubating doxorubicin
      hydrogels at 37 degrees C, chitosan-doxorubicin conjugates were confirmed to be
      degraded into more hydrophilic oligomers by reversed-phase chromatography. In
      vitro cytotoxicity assay using released media from doxorubicin hydrogels showed
      that degraded chitosan-doxorubicin had cytotoxicity comparable to free
      doxorubicin. Athymic nude mice bearing human lung adenocarcinoma were subjected
      to intra-tumoral injections of physical hydrogels. After photo-crosslinking
      injected hydrogels using surgical catheters, tumor sizes, body weights, and
      survivals were measured for 1 month. Released media from doxorubicin hydrogels
      exerted similar cytotoxicities to free doxorubicin, and the tumor volume was
      significantly reduced for 1 month compared to other samples. Thus, doxorubicin
      hydrogels containing doxorubicin conjugates can be employed as a novel injectable
      anti-cancer drug aiming to achieve sustained release of doxorubicin for several
      weeks against solid tumors.

PMID- 19409991
TI  - Extracorporeal photopheresis: from solid organs to face transplantation.
AB  - Composite tissue allotransplantations (CTA), were introduced with the first
      successful hand transplantation and are now a part of reconstructive surgery
      armamentarium. These reconstructive procedures for non life-threatening
      indications remain rare due to adverse effects of the associated lifelong
      immunosuppressive therapy. Indeed, despite recent progress, immunosuppressive
      therapies remain non-specific to the type of donor and still bear significant
      risks of serious side effects. Extracorporeal photopheresis (ECP), also called
      photochemotherapy, has been introduced in the composite tissue
      allotransplantation field as a part of acute rejection treatment in face
      transplantations. ECP has been performed after solid organ transplantations as a
      supportive therapy for acute rejection episodes. It has also been used to treat
      graft versus host diseases, which can occur after bone marrow or stem cell
      transplantations. ECP is also used to treat dermatologic diseases, such as
      cutaneous T-cell lymphoma, or autoimmune diseases, such as scleroderma or
      pemphigus vulgaris. The principle of ECP is to induce leucocyte apoptosis with
      UVA radiation after their presentation by psoralens. These leucocytes are
      immediately re-infused into the patient, where they undergo early apoptosis.
      Following apoptosis, the leucocytes are engulfed by macrophage or other antigen
      presenting cells, such as immature dendritic cells, in an anti-inflammatory
      cytokine environment. The anti-inflammatory cytokine secretion pattern, with a
      switch from TH1 to TH2 for CD4+ lymphocytes, and the engulfment by immature cells
      without co-stimulatory molecules induces anergy, by deleting effector T-cells
      that responded to the presented antigens. An increase in regulatory T-cells (T
      regs) is also induced after ECP and may contribute to allograft acceptance by the
      recipient. ECP has already been used for the great majority of solid organ
      transplantations to cure acute rejection episodes or in an attempt to prevent or
      cure chronic rejections, such as bronchitis obliterans, which occurs after lung
      transplantation. Considering composite tissue allotransplantations, ECP was used
      in two face transplantations after the occurrence of second rejection episodes
      triggered by viral infections. ECP therapy, associated with maintenance
      immunosuppressive therapy and doses of methylprednisolone, and the control of
      viral infection, succeeded to reverse the rejection process without the
      development of other side effects. Despite the fact that the mechanism of action
      of ECP has not been fully elucidated, this therapy could be a useful supportive
      therapy during the treatment of acute rejection episodes in composite tissue
      allotransplantations. In this review, we introduce the interest of ECP
      implementation in CTA in face allotransplantations.

PMID- 19409992
TI  - Effect of the immunosuppressant histone deacetylase inhibitor FR276457 in a
      canine renal transplant model.
AB  - The histone deacetylase (HDAC) inhibitor FR276457, a hydroxamic derivative, was
      identified during chemical library screening and was found to exhibit potent
      inhibitory effects on the activity of mammalian HDACs. It has been shown that
      FR276457 exhibited marked immunosuppressive effects in a rat heterotopic cardiac
      transplant model. To predict clinical efficacy of FR276457, we investigated the
      inhibitory effect of the proliferation of Jurkat cells in vitro and
      immunosuppressive effect of orally administered FR276457 on allograft rejection
      as a monotherapy or in combination with tacrolimus (0.04 mg/kg) injected
      intramuscularly (i.m.) in a canine renal transplant model. Animal survival, the
      plasma creatinine level, and histopathology were evaluated. FR276457 inhibited
      the proliferation of Jurkat cells probably by targeting activity of NF-kappaB.
      FR276457 prolonged the median survival time (MST) of transplanted grafts from
      11.5 days (untreated group) to 29.0 days (FR276457-treated group). FR276457
      administered 1 mg/kg twice a day in combination with tacrolimus prevented
      allograft rejection. In addition, a dose of 1.5 mg/kg twice a day or 5.0 mg/kg
      once a day prolonged the MST from 18 days (control group) to >73 or >90 days,
      respectively. Histopathological analysis showed that FR276457 suppressed the
      score for mononuclear cell infiltration and vasculitis. In conclusion, the HDAC
      inhibitor FR276457 inhibited the proliferation of T cell line established from
      human in vitro. And more, FR276457 clinically prolonged allograft survival when
      administered as a monotherapy, and had additive or synergistic effects when
      combined with tacrolimus with the canine renal transplant model. These results
      showed HDAC inhibitor is a promising biological target for treatment in
      transplant field.

PMID- 19409993
TI  - Analysis of parathyroid graft rejection suggests alloantigen-specific production
      of nitric oxide by iNOS-positive intragraft macrophages.
AB  - BACKGROUND: During acute rejection of organ or tissue allografts T cells and
      macrophages are dominant infiltrating cells. CD4-positive T cells are important
      for the induction of allograft rejection and macrophages are important effector
      cells mediating cytotoxicity via production of nitric oxide (NO) by the inducible
      NO-synthase (iNOS). In the present study we analysed whether the destruction of
      primarily nonvascularised parathyroid allografts is also mediated by iNOS
      positive macrophages. METHODS: Hypocalcaemic Lewis rats received parathyroid
      isografts (from Lewis donors) and allografts (from Wistar Furth donors),
      respectively, under the kidney capsule. Levels of serum calcium above 2 mmol/L
      correlated with normal parathyroid function and below 2 mmol/L with parathyroid
      rejection. Accelerated parathyroid allograft rejection was induced by
      immunisation of Lewis recipients with the allogeneic peptide P1. RESULTS:
      Determination of serum calcium levels is a useful parameter to control
      parathyroid graft function, and therefore to determine allograft rejection.
      Macrophages positive for both major histocompatibility complex (MHC) class II
      molecules and costimulatory molecules accumulated in iso- and allografts, but
      iNOS-positive macrophages were only detectable in allografts in the presence of
      activated CD4-positive T cells. These results confirm a cooperation between
      activated T cells and intragraft macrophages to induce macrophage iNOS
      expression. Recipients immunised with the allogeneic peptide P1 demonstrated
      accelerated rejection of allografts (mean+/-SD: 9.2+/-0.9 days) in contrast to
      nonimmunised animals (mean+/-SD: 15.8+/-1.8 days). Allografts of P1-immunised
      animals were infiltrated faster by activated CD4-positve T cells and, in
      addition, the infiltrates of iNOS-positive macrophages were stronger than those
      in allografts of nonimmunised animals. CONCLUSIONS: Intragraft iNOS-positive
      macrophages seem to be able to produce cytotoxic NO involved in the killing of
      allogeneic cells during the alloimmune response against primarily nonvascularised
      parathyroid organ grafts. Infiltrates of iNOS-negative macrophages found in
      parathyroid isografts were caused by antigen-independent inflammation triggered
      by surgically induced injury. The absence of activated T cells in isografts and
      their presence in allografts underlines their importance in inducing macrophage
      iNOS expression.

PMID- 19409994
TI  - Adoptive transfer of transgenic T cells to study mucosal adjuvants.
AB  - The study of the initiation and regulation of T-cell responses to vaccine
      antigens is of primary importance in the rational design of mucosal adjuvants.
      The detection in vivo of T-cell priming following immunization can be performed
      by using the adoptive transfer model of naive antigen-specific transgenic T cells
      into immunocompetent mice. In this work, we discuss the applications of this
      system for detecting in vivo the primary antigen-specific clonal expansion, the
      phenotype, and the effector function of transgenic T cells following mucosal
      immunization. OVA and the mucosal adjuvant CTB were used as a model vaccine
      formulation and administered by the nasal route to study T-cell priming. T helper
      and T cytotoxic primary proliferation and expression of activation and migration
      markers was observed both in draining and distal sites. This method proved to be
      a powerful tool to study the efficacy of mucosal adjuvants in enhancing T-cell
      priming.

PMID- 19409995
TI  - RNA folding dynamics by single-molecule fluorescence resonance energy transfer.
AB  - Single-molecule fluorescence resonance energy transfer (smFRET) microscopy has
      become an increasingly popular tool to study the structural dynamics of RNA
      molecules. It reveals, in real time, the structural dynamics of these molecules
      that would be otherwise hidden in ensemble-averaged measurements. Here we present
      a detailed protocol for performing smFRET using total internal reflection
      fluorescence microscopy, including RNA preparation, optical setup, separation of
      the dual color channels, sample immobilization and data acquisition and analysis.

PMID- 19409997
TI  - Isolation and functional analysis of RNA polymerase II elongation complexes.
AB  - The elongation phase of transcription by RNA polymerase II (RNAP II) is tightly
      controlled by a large number of transcription elongation factors. Here we
      describe experimental approaches for the isolation of RNAPII elongation complexes
      in vitro and the use of these complexes in the examination of the function of a
      variety of factors. The methods start with formation of elongation complexes on
      DNA templates immobilized to paramagnetic beads. Elongation is halted by removing
      the nucleotides and the ternary elongation complexes are then stripped of factors
      by a high salt wash. The effect of any factor or mixture of factors on elongation
      is determined by adding the factor(s) along with nucleotides and observing the
      change in the pattern of RNAs generated. Association of a factor with elongation
      complexes can be examined using an elongation complex-electrophoretic mobility
      shift assay (EC-EMSA) in which elongation complexes that have been liberated from
      the beads are analyzed on a native gel. Besides being used to dissect the
      mechanisms of elongation control, these experimental systems are useful for
      analyzing the function of termination factors and mRNA processing factors.
      Together these experimental systems permit detailed characterization of the
      molecular mechanisms of elongation, termination, and mRNA processing factors by
      providing information concerning both physical interactions with and functional
      consequences of the factors on RNAPII elongation complexes.

PMID- 19409998
TI  - Translational modifications to improve vaccine efficacy in an oral influenza
      vaccine.
AB  - Oral vaccination using protein antigens is complicated by the degradative effects
      of the inhospitable conditions in the gastrointestinal tract, such as low pH and
      digestive enzymes, nescessitating protection and effective delivery of the
      antigen. The bilosome is a lipid-based, vesicle delivery system incorporating
      bile salts, which is believed to protect the antigen from degradation, and has
      been shown to induce significant antibody responses when delivered orally with
      various vaccines. In translational research, from laboratory bench to industrial
      scale-up, it is necessary to optimise the manufacturing process in order to
      improve efficiency and simplify production, giving a more economical end-product.
      In this study we tested two simplified production methods (3-step and 1-step)
      along with two different storage methods (lyophilised and non-lyophilised), as
      well as looking at the effect of buffer pH. The formulations were assessed in a
      murine system for immunogenicity, alongside characterisation in terms of size and
      antigen entrapment, with the stability of these aspects assessed with respect to
      time. Both lyophilised and non-lyophilised 3-step formulations induced
      significant IgG1, IgG2a and IgA titres, with the lyophilised version showing
      stable size and antigen entrapment up to 9months.

PMID- 19409996
TI  - Raman crystallography of RNA.
AB  - Raman crystallography is the application of Raman spectroscopy to single
      crystals. This technique has been applied to a variety of protein molecules where
      it has provided unique information about biopolymer folding, substrate binding,
      and catalysis. Here, we describe the application of Raman crystallography to
      functional RNA molecules. RNA represents unique opportunities and challenges for
      Raman crystallography. One issue that confounds studies of RNA is its tendency to
      adopt multiple non-functional folds. Raman crystallography has the advantage that
      it isolates a single state of the RNA within the crystal and can evaluate its
      fold, metal ion binding properties (ligand identity, stoichiometry, and
      affinity), proton binding properties (identity, stoichiometry, and affinity), and
      catalytic potential. In particular, base-specific stretches can be identified and
      then associated with the binding of metal ions and protons. Because measurements
      are carried out in the hanging drop at ambient, rather than cryo, conditions and
      because RNA crystals tend to be approximately 70% solvent, RNA dynamics and
      conformational changes become experimentally accessible. This review focuses on
      experimental setup and procedures, acquisition and interpretation of Raman data,
      and determination of physicochemical properties of the RNA. Raman
      crystallographic and solution biochemical experiments on the HDV RNA enzyme are
      summarized and found to be in excellent agreement. Remarkably, characterization
      of the crystalline state has proven to help rather than hinder functional
      characterization of functional RNA, most likely because the tendency of RNA to
      fold heterogeneously is limited in a crystalline environment. Future applications
      of Raman crystallography to RNA are briefly discussed.

PMID- 19409999
TI  - A vaccine against S. pyogenes: design and experimental immune response.
AB  - Streptococcus pyogenes causes severe invasive infections: the post-streptococcal
      sequelae of acute rheumatic fever (RF) and rheumatic heart disease (RHD), acute
      glomerulonephritis, and uncomplicated pharyngitis and pyoderma. Efforts to
      produce a vaccine against S. pyogenes began several decades ago, and different
      models have been proposed. Here, we describe the methodology used in the
      development of a new vaccine model, consisting of both T and B protective
      epitopes constructed as synthetic peptides and recombinant proteins. Two
      adjuvants were tested in an experimental inbred mouse model: a classical Freund's
      adjuvant and a new adjuvant (AFCo1) that induces mucosal immune responses and is
      obtained by calcium precipitation of a proteoliposome derived from the outer
      membrane of Neisseria meningitides B. The StreptInCor vaccine epitope co
      administrated with AFCo1 adjuvant induced mucosal (IgA) and systemic (IgG)
      antibodies as preferential Th1-mediated immune responses. No autoimmune reactions
      were observed, suggesting that the vaccine epitope is safe.

PMID- 19410000
TI  - Mucosal immunization using proteoliposome and cochleate structures from Neisseria
      meningitidis serogroup B induce mucosal and systemic responses.
AB  - Most pathogens either invade the body or establish infection in mucosal tissues
      and represent an enormous challenge for vaccine development by the absence of
      good mucosal adjuvants. A proteoliposome-derived adjuvant from Neisseria
      meningitidis serogroup B (AFPL1, Adjuvant Finlay Proteoliposome 1) and its
      derived cochleate form (Co, AFCo1) contain multiple pathogen-associated molecular
      patterns as immunopotentiators, and can also serve as delivery systems to elicit
      a Th1-type immune response. The present studies demonstrate the ability of
      AFPL1and AFCo1 to induce mucosal and systemic immune responses by different
      mucosal immunizations routes and significant adjuvant activity for antibody
      responses of both structures: a microparticle and a nanoparticle with a
      heterologous antigen. Therefore, we used female mice immunized by intragastric,
      intravaginal, intranasal or intramuscular routes with both structures alone or
      incorporated with ovalbumin (OVA). High levels of specific IgG antibody were
      detected in all sera and in vaginal washes, but specific IgA antibody in external
      secretions was only detected in mucosally immunized mice. Furthermore, antigen
      specific IgG1 and IgG2a isotypes were all induced. AFPL1 and AFCo1 are capable of
      inducing IFN-gamma responses, and chemokine secretions, like MIP-1alpha and MIP
      1beta. However, AFCo1 is a better alternative to induce immune responses at
      mucosal level. Even when we use a heterologous antigen, the AFCo1 response was
      better than with AFPL1 in inducing mucosal and systemic immune responses. These
      results support the use of AFCo1 as a potent Th1 inducing adjuvant particularly
      suitable for mucosal immunization.

PMID- 19410001
TI  - Application of Mu in vitro transposition for high-precision mapping of protein
      protein interfaces on a yeast two-hybrid platform.
AB  - High-precision mapping of regions involved in protein-protein interfaces of
      interacting protein partners is an essential component on a path to understand
      various cellular functions. Transposon-based systems, particularly those
      involving in vitro reactions, offer exhaustive insertion mutant libraries and
      high-throughput platforms for many types of genetic analyses. We present here a
      genetic strategy to accurately map interacting protein regions at amino acid
      precision that is based on transposition-assisted construction, sampling, and
      analysis of a comprehensive insertion mutant library. The methodology integrates
      random pentapeptide mutagenesis of proteins, yeast two-hybrid screening, and high
      resolution genetic footprinting. This straightforward strategy is general, and it
      provides a rapid and easy means to identify critical contact regions in proteins
      without the requirement of prior structural knowledge.

PMID- 19410002
TI  - Using generalized ensemble simulations and Markov state models to identify
      conformational states.
AB  - Part of understanding a molecule's conformational dynamics is mapping out the
      dominant metastable, or long lived, states that it occupies. Once identified, the
      rates for transitioning between these states may then be determined in order to
      create a complete model of the system's conformational dynamics. Here we describe
      the use of the MSMBuilder package (now available at
      http://simtk.org/home/msmbuilder/) to build Markov State Models (MSMs) to
      identify the metastable states from Generalized Ensemble (GE) simulations, as
      well as other simulation datasets. Besides building MSMs, the code also includes
      tools for model evaluation and visualization.

PMID- 19410003
TI  - Lincomycin-induced over-expression of mature recombinant cholera toxin B subunit
      and the holotoxin in Escherichia coli.
AB  - Cholera toxin (CT) B subunit (CTB) was overproduced using a novel expression
      system in Escherichia coli. An expression plasmid was constructed by inserting
      the gene encoding the full-length CTB and the Shine-Dalgarno (SD) sequence
      derived from CTB or from the heat-labile enterotoxin B subunit (LTB) of
      enterotoxigenic E. coli into the lacZalpha gene fragment in the pBluescript SK(+)
      vector. The E. coli strain MV1184 was transformed with each plasmid and then
      cultured in CAYE broth containing lincomycin. Recombinant CTB (rCTB) was purified
      from each cell extract. rCTB was overproduced in both transformants without
      obvious toxicity and was structurally and biologically identical to that of CT
      purified from Vibrio cholerae, indicating that the original SD and CTB signal
      sequences were also sufficient to express rCTB in E. coli. Lincomycin-induced
      rCTB expression was inhibited by mutating the lac promoter, suggesting that
      lincomycin affects the lactose operon. Based on these findings, we constructed a
      plasmid that contained the wild-type CT operon and successfully overproduced CT
      (rCT) using the same procedure for rCTB. Although rCT had an intact A subunit,
      the amino-terminal modifications and biological properties of the A and B
      subunits of rCT were identical to those of CT. These results suggest that this
      novel rCTB over-expression system would also be useful to generate both wild-type
      and mutant CT proteins that will facilitate further studies on the
      characteristics of CT, such as mucosal adjuvant activity.

PMID- 19410006
TI  - Comments on the paper by Pleijel et al. (2008): Vouching for GenBank.

PMID- 19410004
TI  - Molecular and expression analysis of complement component C5 in the nurse shark
      (Ginglymostoma cirratum) and its predicted functional role.
AB  - We present the complete cDNA sequence of shark (Ginglymostoma cirratum) pro-C5
      and its molecular characterization with a descriptive analysis of the structural
      elements necessary for its potential functional role as a potent mediator of
      inflammation (fragment C5a) and initiator molecule (fragment C5b) for the
      assembly of the membrane attack complex (MAC) upon activation by C5 convertase.
      In mammals the three complement activation cascades, the classical, alternative
      and lectin pathways, converge at the activation of C3, a pivotal complement
      protein. It is, however, the subsequent activation of the next complement
      component, C5, which is the focal point at which the initiation of the terminal
      lytic pathway takes place and involves the stepwise assembly of the MAC. The
      effector cytolytic function of complement occurs with the insertion of MAC into
      target membranes causing dough-nut like holes and cell leakage. The lytic
      activity of shark complement results in structurally similar holes in target
      membranes suggesting the assembly of a shark MAC that likely involves a
      functional analogue of C5. The composition of shark MAC remains unresolved and to
      date conclusive evidence has been lacking for shark C5. The gene has not been
      cloned nor has the serum protein been characterized for any elasmobranch species.
      This report is the first to confirm the presence of C5 homologue in the shark.
      GcC5 is remarkably similar to human C5 in overall structure and domain
      arrangement. The GcC5 cDNA measured 5160-bp with 5' and 3' UTRs of 35 bp and 79
      bp, respectively. Structural analysis of the derived protein sequence predicts a
      molecule that is a two-chain structure which lacks a thiolester bond and contains
      a C5 convertase cleavage site indicating that activation will generate two
      peptides, akin to C5b and C5a. The putative GcC5 molecule also contains the C
      terminal C345C/Netrin module that characterizes C3, C4 and C5. Multiple alignment
      of deduced amino acid sequences shows that GcC5 shares more amino acid
      identities/similarities with mammals than that with bony fish. We conclude that
      at the time of emergence of sharks the elaborate mosaic structure of C5 had
      already evolved.

PMID- 19410007
TI  - Phylogeny, taxonomy, and evolution of the endothelin receptor gene family.
AB  - A gene phylogeny provides the natural historical order to classify genes and to
      understand their functional, structural, and genomic diversity. The gene family
      of endothelin receptors (EDNR) is responsible for many key physiological and
      developmental processes of tetrapods and teleosts. This study provides a well
      defined gene phylogeny for the EDNR family, which is used to classify its members
      and to assess their evolution. The EDNR phylogeny supports the recognition of the
      EDNRA, EDNRB, and EDNRC subfamilies, as well as more lineage-specific duplicates
      of teleosts and the African clawed frog. The duplications for these nominal genes
      are related to the various whole-genome amplifications of vertebrates, jawed
      vertebrates, fishes, and frog. The EDNR phylogeny also identifies several gene
      losses, including that of EDNRC from placental and marsupial (therian) mammals.
      When coupled with structural and biochemical information, site-specific analyses
      of evolutionary rate shifts reveal two distinct patterns of potential functional
      changes at the sequence level between therian versus non-therian EDNRA and EDNRB
      (i.e., between groups without and with EDNRC). An analysis of linkage maps and
      tetrapod synteny further suggests that the loss of therian EDNRC may be related
      to a chromosomal deletion in its common ancestor.

PMID- 19410005
TI  - Is the brain the essential in hypertension?
AB  - The brain is typically considered a target for late stage hypertensive disease
      due to the high prevalence of stroke among hypertensive patients. Research is
      reviewed, however, that suggests that the brain is implicated in the initiation
      of high blood pressure and is itself altered by early disease processes. A
      substantial literature establishes neural control of the vasculature and kidney
      as candidate etiological factors in essential hypertension. This research,
      largely done in animals, is now supplemented by behavioral and brain imaging
      studies in humans. This review suggests that the brain and vasculature may be
      independently and concurrently targeted by the factors inducing essential
      hypertension. Early stage hypertension is associated with cognitive deficits,
      altered cerebral blood flow support for cognitive processing, and decreased grey
      matter in specific cortical regions. Pharmacological reversal of hypertension is
      less successful in patients with premature brain aging and fails to reverse
      either the progression of functional or structural changes within the cerebral
      cortex. Furthermore, magnetic resonance imaging Blood Oxygen Level-Dependent
      (BOLD) responses during psychological challenge differ between normotensive
      individuals at risk and those not at risk for hypertension because of their
      exaggerated blood pressure responses to psychological challenge. Further
      examination of mechanisms of action and early influences of the disease on the
      brain are required to understand the pathophysiological mechanisms having
      concurrent influences on the brain and the peripheral vasculature.

PMID- 19410008
TI  - Cellular and molecular studies of the initial process of the photodynamic therapy
      in HEp-2 cells using LED light source and two different photosensitizers.
AB  - Photodynamic therapy is an attractive therapeutic procedure for a variety of
      neoplastic and non-neoplastic disorders that involve a tumor localizing
      photosensitizer that induces cytotoxicity when activated by a particular
      wavelength of light. Considering the acceptability of the phthalocyanine
      photosensitizers, we began to address initial cellular and molecular aspects
      involved in the therapy that leads to apoptosis or necrosis. After HEp-2 cells
      had been incubated for 1h with aluminium tetrasulfonate chloride (AlPcS(4)) or
      zinc phthalocyanines (ZnPc) at 10microM, they were irradiated with an LED
      prototype (640nm, 70mW, 4.5J/cm(2)) and subsequently analyzed at 0 and 3h after
      the irradiation through MTT, fluorescence microscopy, Annexin V-PI staining and
      gene transcription analysis. Based on the results we can address that the two
      photosensitizers led to 2 different death pathways; for AlPcS(4), the results
      suggest an initial process of intrinsic death pathway; and for ZnPc, a prostanoid
      mediated activation of death machinery is suggested.

PMID- 19410009
TI  - A regulatory role for protease-activated receptor-2 in motivational learning in
      rats.
AB  - Serine proteases such as tissue plasminogen activator (tPA), thrombin and
      neuropsin influence hippocampal plasticity involved in learning and memory by
      facilitating both synaptic remodelling and long-term potentiation. Given our
      previous findings that trypsin and its receptor, protease-activated receptor-2
      (PAR2), are both highly expressed in pyramidal neurons of the hippocampus and
      that activation of PAR2 attenuates 'pathogenic' plasticity related to epilepsy,
      we wished to determine the role for PAR2 in normal, non-pathological hippocampal
      plasticity related to learning and memory. In a strain of rat that show high
      basal levels of anxiety, the Genetic Absence Epilepsy Rats from Strasbourg
      (GAERS), peripheral administration of the PAR2 peptide agonist, SLIGRL (1.5 mg/kg
      s.c.), induced distinct deficits in experience-dependent learning both in the
      test-retest paradigm of the elevated-plus maze and in the Morris water maze. In
      separate, conscious rats with indwelling intra-cerebroventricular cannulae,
      SLIGRL rapidly appeared in cerebrospinal fluid (CSF) following peripheral
      administration and had a half-life in CSF of approximately 25 min. These results
      suggest that activation of central PAR2 with brain accessible peptide agonists
      causes a temporary deficit in the formation and/or recollection of experience
      dependent learning and memory.

PMID- 19410010
TI  - Cloning, characterization and expression of ferritin subunit from clam Meretrix
      meretrix in different larval stages.
AB  - Shell formation is one of the important events during larval development and
      metamorphosis in bivalves. However, the molecular mechanisms and environmental
      cues regulating shell initiation and growth are unclear. Here, we report that
      ferritin, a principal protein for biological iron storage and metabolism, might
      play a role in larval shell development of the bivalve mollusk Meretrix meretrix.
      A full-length ferritin subunit cDNA, named as MmeFer, was cloned and
      characterized. The MmeFer mRNA expression in different developmental stages, from
      trochophore to post larvae, was analyzed by real-time reverse transcription
      polymerase chain reaction (RT-PCR). MmeFer mRNA expression in larvae of later
      developmental stages increased at least 8-fold following trochophores. Moreover,
      the temporal and spatial expressions of MmeFer mRNA were examined by whole mount
      in situ hybridization. In the trochophore stage, MmeFer was detectable where it
      was supposed to be for shell initiation. In the later developmental stages,
      MmeFer was found near digestive glands and mantle that secret larval shell.
      MmeFer expression was also detected in larvae cultured in artificial seawater
      with different iron concentrations ranging from 0 to 100 microM. These results
      suggest that ferritin may play a role in the shell formation of mollusks.

PMID- 19410012
TI  - Navigating structure-activity landscapes.
AB  - The problem of how to explore structure-activity relationships (SARs)
      systematically is still largely unsolved in medicinal chemistry. Recently, data
      analysis tools have been introduced to navigate activity landscapes and to assess
      SARs on a large scale. Initial investigations reveal a surprising heterogeneity
      among SARs and shed light on the relationship between 'global' and 'local' SAR
      features. Moreover, insights are provided into the fundamental issue of why
      modeling tools work well in some cases, but not in others.

PMID- 19410011
TI  - Preservation of the in vivo state of mitochondrial network for ex vivo
      physiological study of mitochondria.
AB  - Over the course of many years our laboratory has been engaged in the study of
      physiological functions of mitochondria ex vivo. We showed that the unavoidable
      destruction of mitochondrial-reticular network during traditional isolation of
      the mitochondria diminishes the observable ex vivo changes of mitochondrial
      processes in vivo. Comparing preparations obtained from quiescent and stressed
      rats, we found that the great difference in size of assemblies of mitochondria
      preserved in homogenate disappears when it is diluted for the measurement of
      respiration. This also leads to a decrease in the difference between respiration
      of mitochondria from quiescent and stressed animals. We developed a new method
      that provides ex vivo stable preservation of the in vivo network using a
      cytochemical procedure on glass-adhered lymphocytes in blood smear. We radically
      changed the incubation medium for the measurement of dehydrogenase activity that
      excludes an artefact of succinate dehydrogenase hyperactivation ex vivo by non
      physiological components of the traditionally used solution. Our method made it
      possible to observe ex vivo two- to eightfold increase in succinate dehydrogenase
      activity by adrenaline in vivo, while the activity of alpha-ketoglutarate
      dehydrogenase changed reciprocally. The data obtained show that the structure
      changes of the network play an important role in physiological regulation of
      mitochondrial functions. Thus, it may be possible to correct mitochondrial
      dysfunctions in the organism by substances supporting the stability of
      mitochondrial network. The developed method is non-invasive, informative and,
      therefore, is convenient for clinical investigations, particularly of
      mitochondrial diseases.

PMID- 19410014
TI  - Epilepsy impact on aspects of school life of children from different cultural
      populations in Thrace, Greece.
AB  - Epilepsy influences the school life of children. The aims of this study were to
      (1) assess absenteeism and participation in sports activities, (2) investigate
      whether parents inform school and children inform their classmates, and (3)
      determine which factors influence these school aspects. Children from both
      Christian and Muslim families were enrolled and different cultural variables were
      prospectively documented. A total of 62 children with epilepsy (mean age: 10.2+/
      3.3 years, range: 6-18) participated in the present study. Univariate analysis
      and multivariate logistic regression models were used to explore potential
      factors that could influence school life. Absenteeism was correlated with shorter
      disease duration, severity, lower parental educational level, and knowledge of
      epilepsy. Age>12 was associated with nonparticipation in activities. Schools were
      informed by 84% of families, and classmates, by 22.6% of children. In conclusion,
      better knowledge of epilepsy resulted in fewer missed school days. The majority
      of children did not discuss their disease, and children from the two populations
      with different religions did not differ significantly in the school aspects
      examined. These findings suggest a probable positive effect of educational
      programs on the issue of daily school life.

PMID- 19410013
TI  - The roles of phospholipase D in EGFR signaling.
AB  - Epidermal growth factor receptor (EGFR) is a representative model of receptor
      tyrosine kinases (RTKs), and offers a means of understanding their common
      principles and fundamental mechanisms. Furthermore, EGFR plays an essential role
      in cell proliferation and migration, and the disruption of EGFR signaling has
      been implicated in the development and growth of cancer. Phospholipase D (PLD) is
      a key mediator of EGFR function, and can be directly regulated by upstream
      binding partners in an EGF-dependent manner. PLD regulates downstream molecules
      by generating phosphatidic acid (PA), but it also dynamically interacts with a
      variety of intracellular molecules and these interactions spatiotemporally
      regulate EGFR function and serve as a hub that orchestrates signaling flow. This
      review summarizes the interrelationship between PLD and its binding molecules in
      the context of EGFR signaling, and addresses the roles of PLD in the mediation
      and coordination of this signaling.

PMID- 19410015
TI  - Current and past smoking significantly increase risk for Barrett's esophagus.
AB  - BACKGROUND & AIMS: Barrett's esophagus (BE) is the precursor to esophageal
      adenocarcinoma; the incidence of this cancer is rapidly increasing in Western
      populations. However, few population-based studies of BE have been conducted, so
      little is known about potentially modifiable causes of this disease. METHODS: The
      study included patients with newly diagnosed BE, confirmed by histology and
      categorized as simple BE (without dysplasia, n = 285) or dysplastic BE (with
      dysplasia, n = 108). We recruited 2 separate control groups: endoscopy patients
      with acute inflammatory changes (inflammation controls, n = 313) and population
      controls sampled from a population register (n = 644). Data were collected
      through standardized questionnaires and telephone interviews. We fit logistic
      regression models to calculate odds ratios (ORs) for BE associated with salient
      exposures by using each set of controls. RESULTS: Relative to never smokers,
      risks of simple BE were significantly higher among former smokers (OR, 2.39; 95%
      confidence interval, 1.59-3.60) and current smokers (OR, 2.41; 95% confidence
      interval, 1.39-4.17), compared with population controls. Smoking conferred more
      than a 4-fold increase in risk for dysplastic BE; this increase in risk remained
      long after individuals quit smoking. We found no conclusive association between
      BE and passive smoking and no evidence of independent associations between body
      mass index (BMI) and simple BE or dysplastic BE, after adjusting for reflux and
      other factors. Analyses with inflammation controls produced qualitatively similar
      risk estimates for smoking and BMI to those obtained for population controls, but
      they were markedly attenuated for reflux, as expected. CONCLUSIONS: Current and
      past smoking significantly increases risk for BE, but BMI does not, after
      adjustment for the effect of reflux.

PMID- 19410016
TI  - A 24-year-old pregnant woman with inflammatory bowel disease.

PMID- 19410017
TI  - A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic
      cancer.
AB  - BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) and pancreatic cancer (PaC) have
      similar presentations; a diagnostic strategy is needed to distinguish the 2
      diseases. METHODS: We compared computed tomography images (for pancreas and other
      organ involvement), serum IgG4 levels, histology data, and the response to
      steroids between patients with AIP (n = 48) and those with PaC (n = 100).
      RESULTS: Pancreatic imaging findings stratified patients into 3 groups. Group 1
      was highly suggestive of AIP, with diffuse pancreatic enlargement without group 3
      features (n = 25, 100% AIP). Group 2 was indeterminate, with normal-sized
      pancreas or focal pancreatic enlargement without group 3 features (n = 20, 75%
      AIP). Group 3 was highly suggestive of PaC, with presence of >1 low-density mass,
      pancreatic duct cutoff, or upstream pancreatic atrophy (n = 103, 92% PaC).
      Although all patients in group 1 had AIP, only 20 of the 25 patients had
      increased serum IgG4 levels and/or other organ involvement. Of the patients in
      groups 2 and 3 who did not have cancer, all those with serum IgG4 levels >2-fold
      the upper limit of normal or a combination of increased serum IgG4 levels and
      other organ involvement (n = 15) had AIP. In AIP subjects without supportive
      serologic evidence or other organ involvement (n = 14), diagnosis required
      pancreatic core biopsy (n = 7), steroid trial (n = 5), or resection (n = 2).
      CONCLUSIONS: PaC can be distinguished from AIP by pancreatic imaging, measurement
      of serum IgG4 levels, and determination of other organ involvement. However, a
      pancreatic core biopsy, steroid trial, or surgery is required for diagnosis in
      approximately 30% of patients with AIP.

PMID- 19410018
TI  - A prospective study of conventional and expanded coagulation indices in
      predicting ulcer bleeding after variceal band ligation.
AB  - BACKGROUND & AIMS: There is controversy over whether coagulation status predicts
      bleeding caused by ulceration after esophageal varices band ligation (EVL).
      METHODS: EVL was performed for primary (n = 45) or secondary (n = 105)
      prophylaxis in 150 patients with cirrhosis (Child A, n = 74, 49%; Child B, n =
      42, 28%; Child C, n = 34, 23%). International normalized ratio (INR) and platelet
      counts were assessed in all. In 92 patients, levels of factor V, fibrinogen, D
      dimer, protein C and protein S, von Willebrand factor, and thromboelastography
      (TEG) were assessed. Platelet count <50 x 10(3)/mm(3) and INR >1.5 were
      considered high-risk cutoff for bleeding. Conversely, platelet count >or=50 x
      10(3)/mm(3) with INR <or=1.5 were safe cutoffs. RESULTS: Overall, 11 patients
      (7.3%) had post-EVL ulcer bleeding. Bleeding occurred in 5 patients with Child
      A/B (4.3%) and 6 patients with Child C (17%) (P = .0174 for Child A/B versus
      Child C). Eight patients with bleeding were among the 110 below the cutoff for
      INR and platelet count, whereas only 3 of the patients with bleeding were among
      the 40 patients with purported high-risk values (P = 1.0). Among the 92 patients
      with expanded coagulation tests, bleeding occurred in 5. There was no difference
      in any of the coagulation parameters, including overall TEG patterns, between
      patients who did and did not bleed. CONCLUSIONS: Post-EVL ulcer bleeding was
      associated with Child C status but not with conventional or expanded coagulation
      indices in cirrhotic patients without renal failure or infection undergoing
      elective EVL. These results call into question the common use of prophylactic
      procoagulants in the elective setting.

PMID- 19410019
TI  - Bouveret's syndrome: unusual case with unusual therapeutic approach.

PMID- 19410020
TI  - Phenylalanine 35 and tyrosine 82 are involved in the uptake and release of ligand
      by porcine odorant-binding protein.
AB  - Structural and molecular dynamics studies have pointed out the role of aromatic
      residues in the uptake of ligand by porcine odorant-binding protein (pOBP). The
      shift of Tyr82 from its position during the opening of the binding cavity has
      been shown, and was supposed to participate in the entrance of the ligand.
      Several Phe residues in the vicinity of Tyr82 could also participate in the
      binding process. To clarify their involvement, we performed molecular dynamics
      studies to simulate the dissociation of undecanal, a ligand previously co
      crystallized with pOBP. The results confirmed the key-role of Tyr82 and pointed
      out the participation of Phe35 in controlling the reorientation of undecanal
      towards the exit. To bring experimental support to both published (binding) and
      present simulations (dissociation), we have mutated these two residues and over
      expressed the wild type pOBP, the two single mutants and the double mutant in the
      yeast Pichia pastoris. As fluorescence spectroscopy implies the uptake of the
      fluorescent probe and release in displacement experiments, we monitored the
      binding ability of the four proteins for 1-aminoanthracene (1-AMA). The
      experimental results indicated that both residues are involved in the uptake of
      ligand as the three mutated proteins were unable to bind 1-AMA, contrary to the
      wild type recombinant pOBP that bound 1-AMA with the expected affinity.

PMID- 19410021
TI  - The change in the principle of performing laparoscopic adrenalectomy from small
      to large masses.
AB  - BACKGROUND: Laparoscopic adrenalectomy has become the gold standard in most
      patients with adrenal tumors. It is unclear; however, at what size an adrenal
      neoplasm should be resected by means of an open or a laparoscopic approach. The
      aim of the present study was to compare the outcomes of laparoscopic
      adrenalectomy for large tumors with smaller tumors. METHODS: A prospective study
      of patients who underwent adrenalectomy during the period 2006-2009 was
      undertaken. The patients were divided into 2 groups according to the tumor size.
      Group 1 (n=29) consisted of patients presenting tumors smaller than 5 cm in
      diameter; group 2 (n=31) consisted of patients with tumors larger than 5 cm in
      diameter. RESULTS: Two of the 29 tumors in group 1 (6.8%) were malignant at final
      histology. However, 11 of the 31 tumors in group 2 (35.4%) were malignant. There
      were no significant differences between operating time and complications of
      groups 1 and 2. The intra-operative blood loss was significantly lower in group 1
      than in group 2. CONCLUSION: Laparoscopic adrenalectomy is a reasonable procedure
      for selected large adrenal tumors when a complete resection is technically
      feasible and there is no evidence of local invasion.

PMID- 19410022
TI  - Associated malformations in patients with esophageal atresia.
AB  - Esophageal atresia is a common type of congenital malformation. The etiology of
      esophageal atresia is unclear and its pathogenesis is controversial. Because
      previous reports have inconsistently noted the type and frequency of
      malformations associated with esophageal atresia, we conducted this study in a
      geographically well-defined population, evaluating the birth prevalence of
      esophageal atresia and associated malformations ascertained between 1979 and 2003
      in 334,262 consecutive births. Of the 99 patients with esophageal atresia, 46
      (46.5%) had associated malformations. These included patients with chromosomal
      abnormalities (8 patients, 8%); non-chromosomal recognized syndromes (4
      patients), including one each CHARGE syndrome, Fanconi anemia, Fryns syndrome,
      and Opitz G/BBB syndrome; associations including VACTERL (10 patients), and one
      schisis; one oculo-auriculo-vertebral spectrum; one malformation complex, a
      sirenomelia, and non-syndromic multiple congenital anomalies (MCA) (21 patients,
      21%). Malformations of the cardiovascular system (24%), urogenital system (21%),
      digestive system (21%), musculoskeletal system (14%), and central nervous system
      (7%) were the most common other congenital malformations occurring in patients
      with esophageal atresia and non-syndromic MCA. We observed a high prevalence of
      total malformations and specific patterns of malformations associated with
      esophageal atresia which emphasizes the need to evaluate all patients with
      esophageal atresia for possible associated malformations. The malformations
      associated with esophageal atresia could be classified into a recognizable
      malformation syndrome or pattern in 25 out of 46 patients (54%).

PMID- 19410023
TI  - Mustn1 is expressed during chondrogenesis and is necessary for chondrocyte
      proliferation and differentiation in vitro.
AB  - Mustn1 encodes a small nuclear protein expressed specifically in the
      musculoskeletal system that was originally identified as a strongly up-regulated
      gene during bone regeneration, especially in fracture callus proliferating
      chondrocytes. Further experiments were undertaken to investigate its expression
      and role during chondrogenesis. Initially, whole mount mouse in situ
      hybridization was carried out and revealed Mustn1 expression in areas of active
      chondrogenesis that included limb buds, branchial arches and tail bud. To
      elucidate its function, experiments were carried out to perturb Mustn1 by
      overexpression and silencing in the pre-chondrocytic RCJ3.1C5.18 (RCJ) cell line.
      In these cells, Mustn1 is normally differentially regulated, with a spike in
      expression 2 days after induction of differentiation. Further, Mustn1 was
      successfully overexpressed in multiple RCJ cell lines by approximately 2-6 fold,
      and reduced to approximately 32-52% in silenced cell lines as compared to
      parental Mustn1 levels. Overexpressing, silenced, control, and parental RCJ cell
      lines were assayed for proliferation and differentiation. No statistically
      significant changes were observed in either proliferation or proteoglycan
      production when Mustn1 overexpressing lines were compared to parental and
      control. By contrast, both proliferation rate and differentiation were
      significantly reduced in Mustn1 silenced cell lines. Specifically, RNAi silenced
      cell lines showed reductions in populations of approximately 55-75%, and also
      approximately 34-40% less matrix (proteoglycan) production as compared to
      parental and random control lines. Further, this reduction in matrix production
      was accompanied by significant downregulation of chondrogenic marker genes, such
      as Sox9, Collagen type II (Col II), and Collagen type X (Col X). Lastly,
      reintroduction of Mustn1 into a silenced cell line rescued this phenotype,
      returning proliferation rate, matrix production, and chondrogenic marker gene
      expression back to parental levels. Taken together these data suggest that Mustn1
      is a necessary regulator of chondrocyte function.

PMID- 19410024
TI  - Influence of the proportion of particulate autogenous bone graft/platelet-rich
      plasma on bone healing in critical-size defects: an immunohistochemical analysis
      in rat calvaria.
AB  - This immunohistochemical analysis evaluated the influence of the proportion of
      particulate autogenous bone (AB) graft/platelet-rich plasma (PRP) on bone healing
      in surgically created critical-size defects (CSD) in rat calvaria. 25 rats were
      divided into 5 groups: C (control), AB, AB/PRP-50, AB/PRP-100 and AB/PRP-150. A 5
      mm diameter critical-size defect was created in the calvarium of each animal. In
      Group C, defect was filled by blood clot only. In Group AB, defect was filled
      with AB graft. In Groups AB/PRP-50, AB/PRP-100 and AB/PRP-150, defects were
      filled with AB graft combined with 50, 100 and 150 microl of PRP, respectively.
      Animals were euthanized at 30 days post-operative. Osteocalcin (OC) and
      osteopontin (OP) immunohistochemical staining were performed. OP-positive and OC
      positive cells were quantified. The amount of vital bone (VBA) and remaining bone
      graft particles (RPA) were calculated as percentage of the total area of the
      original defect. Data were statistically analyzed (ANOVA, Tukey, p<0.05). Group
      AB/PRP-100 presented a significantly higher number of OP-positive cells than
      groups C, AB/PRP-50 and AB/PRP-150 (p<0.05) and also a significantly higher
      number of OC-positive cells than all of the other groups (p<0.05). The number of
      OP-positive cells in Group AB/PRP-150 was significantly lower than in Group AB
      (p<0.05). Statistically significant differences were not found between groups
      with regard to either VBA or RPA (p>0.05). However, clear trends were indicated
      by an increase in VBA in Group AB/PRP-100 when compared to groups C, AB and
      AB/PRP-150 and an increase in RPA in Group AB/PRP-150 when compared to groups AB,
      AB/PRP-50 and AB/PRP-100. The proportion AB graft/PRP seems to influence bone
      healing in CSD in rat calvaria. The highest expression of osteocalcin and
      osteopontin, and thus the most developed healing, was found in Group AB/PRP-100
      indicating that there may be an optimal proportion beyond which increasing the
      concentration PRP is deleterious.

PMID- 19410025
TI  - Tissue inhibitors of matrix metalloproteinases in platelets and megakaryocytes: a
      novel organization for these secreted proteins.
AB  - OBJECTIVE: Expression of tissue inhibitors of matrix metalloproteinases (TIMPs)
      is one way that activated platelets intervene in tissue remodeling and
      angiogenesis. Our study was designed to investigate their synthesis in
      megakaryocytes (MKs) and their storage in platelets. MATERIALS AND METHODS: TIMP
      expression in MKs derived from blood CD34(+) progenitor cells of normal donors
      and a megakaryocytic cell line (CHRF-288-11) grown in serum-free conditions and
      platelets from normal donors or two patients with gray platelet syndrome was
      studied by immunofluorescence labeling, reverse transcription-polymerase chain
      reaction, and western blotting. RESULTS: Biosynthesis of TIMPs 1-4 in MKs was
      indicated by presence of their messenger RNAs as shown by polymerase chain
      reaction and of their proteins. Immunofluorescence labeling suggested a primarily
      granular localization of TIMPs in MKs and platelets. But when colocalization with
      von Willebrand factor, fibrinogen, P-selectin, and other alpha-granule proteins
      was assessed in platelets by confocal microscopy, TIMP-1, -2, and -4 were
      localized as distinct fluorescent patches apart from the established alpha
      granule markers and largely independent of platelet metalloproteinases. TIMP-3
      differed for it also had an alpha-granule location. Western blotting confirmed
      the presence of TIMPs 1-4 in platelets and thrombin activation resulted in their
      extensive release to the medium. Platelets from two patients with gray platelet
      syndrome, congenitally deficient in alpha-granules, showed sparse labeling of von
      Willebrand factor and fibrinogen confined to vestigial alpha-granules; however,
      localization of the TIMPs was unchanged. CONCLUSIONS: TIMPs are synthesized and
      organized in MKs and platelets independently of other secreted proteins present
      in alpha-granule pools.

PMID- 19410026
TI  - Sampling uncertainty in medical research.
AB  - OBJECTIVE: Statistical analysis is ubiquitous in medical research, but
      fundamental statistical principles are not always well understood, which has
      negative effects for both authors and readers of scientific papers. The purpose
      of this brief review is to provide a methodological overview on populations,
      samples, analysis units and sampling uncertainty to facilitate an increased
      understanding of statistical concepts.

PMID- 19410027
TI  - The "placebo" response in osteoarthritis and its implications for clinical
      practice.
AB  - Many observations support a major biological effect from the way in which people
      interpret the meaning of each component of their medical experience and the
      context in which this occurs. A recent systematic review of randomised controlled
      trials in osteoarthritis has demonstrated that the effect size of "placebo" is
      substantial and is usually greater than that obtained from the specific effect of
      an individual treatment. In the context of a randomised controlled trial, such a
      large placebo or "meaning" response is considered a nuisance, but in the context
      of clinical practice the optimisation of such meaning and contextual responses,
      through enhanced "care", could greatly benefit people who suffer from
      osteoarthritis.

PMID- 19410028
TI  - Development of osteoarthritic features in estrogen receptor knockout mice.
AB  - OBJECTIVE: Estrogens are suggested to play a role in the development of
      osteoarthritis as indicated by the increased prevalence in women after menopause.
      We studied whether deletion of the estrogen receptor (ER) alpha, beta, or both in
      female mice results in cartilage damage, osteophytosis, and changes in
      subchondral bone of skeletally mature animals. METHODS: We studied knee joints of
      6-month-old female ERalpha-/-, ERbeta-/-, and (double) ERalpha-/-beta-/- mice and
      their wild type (wt) littermates. The presence and size of osteophytes and
      osteoarthritic changes in cartilage were analyzed using histology. Changes in
      subchondral plate and trabecular bone were studied using micro-CT. RESULTS: In
      ERalpha-/-beta-/- mice, we observed an increase in number and/or size of
      osteophytes and thinning of the lateral subchondral plate. However, cartilage
      damage was not different from wt. In ERalpha-/- or ERbeta-/- mice, no significant
      differences in cartilage damage score, osteophyte formation, or subchondral plate
      thickness were found. The bone volume fraction of the epiphyseal trabecular bone
      was unchanged in ERalpha-/- mice, increased in ERbeta-/- mice, and decreased in
      ERalpha-/-beta-/- mice. CONCLUSIONS: We conclude that deletion of both ERs leads
      to increased osteophytosis, but deletion of one or both ERs does not lead to
      overt cartilage damage in 6-month-old mice.

PMID- 19410029
TI  - Ability of dGEMRIC and T2 mapping to evaluate cartilage repair after
      microfracture: a goat study.
AB  - OBJECTIVE: To investigate the ability of delayed gadolinium-enhanced magnetic
      resonance (MR) imaging of cartilage (dGEMRIC) and T2 mapping to evaluate the
      quality of repair tissue after microfracture. DESIGN: Twelve knees from 12 goats
      were studied. An osteochondral defect (diameter, 6mm; depth, 3mm) with
      microfracture was created in the weight-bearing aspect of both the medial and
      lateral femoral condyles. Goats were euthanized at 24 weeks (n=6) and 48 weeks
      (n=6) postsurgery. Pre-contrast R1 (R1pre) and post-contrast R1 (R1post)
      measurements for dGEMRIC and a pre-contrast T2 measurement for T2 mapping were
      performed with a 3T MR imaging system. MR imaging findings were compared with
      histological and biochemical assessments. RESULTS: In native cartilage,
      significant correlations were observed between the R1post and the
      glycosaminoglycan (GAG) concentration, as well as DeltaR1 (difference between the
      R1pre and R1post) and the GAG concentration (P<0.05). In repair tissue, a
      significant correlation was observed between DeltaR1 and the GAG concentration
      (P<0.05), but not between the R1post and the GAG concentration. In both repair
      tissue and native cartilage, no correlation was observed between T2 and the water
      concentration or between T2 and the hydroxyproline (HP) concentration. A zonal
      variation of T2 and a clear dependence of T2 on the angles relative to B0 were
      observed in native cartilage, but not in repair tissue. CONCLUSION: dGEMRIC with
      DeltaR1 measurement might be useful for the evaluation of the GAG concentration
      in repair tissue after microfracture. T2 mapping might be useful for the
      differentiation of repair tissue after microfracture from native cartilage;
      however, its potential to assess the specific biochemical markers in native
      cartilage as well as repair tissue may be limited.

PMID- 19410030
TI  - Systematic review of non-surgical therapies for osteoarthritis of the hand: an
      update.
AB  - OBJECTIVE: To update our earlier systematic review which evaluated all published
      randomized controlled trials (RCTs) evaluating pharmacological and non
      pharmacological therapies in patients with hand osteoarthritis (OA). Surgical
      therapies were not evaluated. METHOD: RCTs published between August 2004 and
      February 2008 were added to the original systematic review. RESULTS: A total of
      44 RCTs evaluating various pharmacological and non-pharmacological therapies in
      hand OA were analyzed in this update. Generally, these RCTs were of low quality.
      RCTs were weakened by a lack of consistent case definition and by a lack of
      standardized outcome assessments. The methods used for randomization, blinding,
      and allocation concealment were rarely described. The number and location of
      symptomatic hand joints per treatment group at baseline was usually not stated.
      The number and location of evaluated hand joints at the end of the study was also
      usually not stated. A meta-analysis could not be performed since most of the
      treatments studied did not have more than one identical comparison to allow
      pooling of the data. CONCLUSIONS: It is apparent that hand OA is a more complex
      area in which to study the efficacy of therapies when compared to hip and knee
      OA. The recently published OARSI Consensus Recommendations will improve the
      design and conduct of future RCTs in hand OA.

PMID- 19410031
TI  - Investigation of the frictional response of osteoarthritic human tibiofemoral
      joints and the potential beneficial tribological effect of healthy synovial
      fluid.
AB  - OBJECTIVE: This study tests the hypothesis that the natural progression of
      osteoarthritis (OA) in human joints leads to an increase in the friction
      coefficient. This hypothesis is based on the expectation that the wear observed
      in OA may be exacerbated by higher friction coefficients. A corollary hypothesis
      is that healthy synovial fluid (SF) may help mitigate the increase in the
      friction coefficient in diseased joints. DESIGN: The friction coefficient of
      human tibiofemoral joints with varying degrees of OA was measured in healthy
      bovine SF and physiological buffered saline (PBS). Two testing configurations
      were adopted, one that promotes sustained cartilage interstitial fluid
      pressurization to investigate the effectiveness of this mechanism with advancing
      OA, and another that allows interstitial fluid pressure to subside to investigate
      the effectiveness of boundary lubrication. RESULTS: Seven specimens were visually
      staged to be normal or mildly degenerated (stages< or =2 on a scale of 1 to 4)
      and nine others had progressive degeneration (stages>2 and< or =3). No
      statistical differences were found in the friction coefficient with increasing
      OA, whether in migrating or stationary contact area configurations; however, the
      friction coefficient was significantly lower in SF than PBS in both
      configurations. CONCLUSIONS: The friction coefficient of human tibiofemoral
      cartilage does not necessarily increase with naturally increasing OA, for visual
      stages ranging from 1 to 3. This outcome may be explained by the fact that
      interstitial fluid pressurization is not necessarily defeated by advancing
      degeneration. This study also demonstrates that healthy SF decreases the friction
      coefficient of OA joints relative to PBS.

PMID- 19410032
TI  - Prevalence of radiographic knee osteoarthritis and its association with knee pain
      in the elderly of Japanese population-based cohorts: the ROAD study.
AB  - OBJECTIVE: We investigated the prevalence of radiographic knee osteoarthritis
      (OA) and knee pain in the Japanese elderly using a large-scale population of a
      nationwide cohort study, Research on Osteoarthritis Against Disability (ROAD),
      and examined their association. METHODS: From the baseline survey of the ROAD
      study, 2,282 participants > or =60 years (817 men and 1,465 women) living in
      urban, mountainous and seacoast communities were analyzed. The radiographic
      severity at both knees was determined by the Kellgren/Lawrence (KL) grading
      system. KL> or =2 and KL> or =3 knee OA were examined separately to assess
      osteophytosis and joint space narrowing (JSN). RESULTS: The prevalence of KL> or
      =2 OA (47.0% and 70.2% in men and women, respectively) was much higher than that
      of previous studies in Caucasians, while that of KL> or =3 OA was not much
      different in men. Age, BMI, female sex and rural residency were risk factors for
      radiographic knee OA, knee pain and their combination. The prevalence of knee
      pain was age-dependent in women, but not in men. Knee pain was more strongly
      associated with KL> or =3 OA than with KL=2, and the association was higher in
      men than in women. Female sex was a strong risk factor even in the subgroup
      without radiographic knee OA (KL=0/1). CONCLUSION: The present cross-sectional
      study revealed a high prevalence of radiographic knee OA in the Japanese elderly.
      Knee pain was strongly associated with JSN especially in men, while women tended
      to have knee pain even without radiographic OA.

PMID- 19410033
TI  - Multi-language translation and cross-cultural adaptation of the OARSI/OMERACT
      measure of intermittent and constant osteoarthritis pain (ICOAP).
AB  - AIM: To conduct a multi-language translation and cross-cultural adaptation of the
      Intermittent and Constant OsteoArthritis Pain (ICOAP) questionnaire for hip and
      knee osteoarthritis (OA). METHODS: The questionnaires were translated and cross
      culturally adapted in parallel, using a common protocol, into the following
      languages: Czech, Dutch, French (France), German, Italian, Norwegian, Spanish
      (Castillan), North and Central American Spanish, Swedish. The process was
      conducted following five steps: (1)--independent translation into the target
      language by two or three persons; (2)--consensus meeting to obtain a single
      preliminary translated version; (3)--backward translation by an independent
      bilingual native English speaker, blinded to the English original version; (4)-
      final version produced by a multidisciplinary consensus committee; (5)--pre
      testing of the final version with 10-20 target-language-native hip and knee OA
      patients. RESULTS: The process could be followed and completed in all countries.
      Only slight differences were identified in the structure of the sentences between
      the original and the translated versions. A large majority of the patients felt
      that the questionnaire was easy to understand and complete. Only a few minor
      criticisms were expressed. Moreover, a majority of patients found the concepts of
      constant pain and pain that comes and goes to be of a great pertinence and were
      very happy with the distinction. CONCLUSION: The ICOAP questionnaire is now
      available for multi-center international studies.

PMID- 19410034
TI  - The prognostic value of the clinical ACR classification criteria of knee
      osteoarthritis for persisting knee complaints and increase of disability in
      general practice.
AB  - OBJECTIVE: To assess the prognostic value of the clinical American College of
      Rheumatism (ACR) classification criteria of knee osteoarthritis (OA) on
      persisting knee complaints and increase of disability in adult patients with knee
      pain in general practice after 1-year follow-up. METHODS: Patients (aged >35
      years) consulting for non-traumatic knee complaints in general practice were
      enrolled in the study. At baseline and 1-year follow-up knee complaints and
      function were assessed by questionnaires and a physical examination was
      performed. The prognostic value of fulfilling the clinical ACR criteria of knee
      OA at baseline on the outcomes persisting knee complaints and increase of
      disability was determined. RESULTS: 549 patients were included in the study of
      which 480 (87.4%) were available for follow-up. The studied population consisted
      of 236 (49.2%) women with mean age 53.6 [standard deviation (sd) 11.3], mean body
      mass index (BMI) 27.1 (sd 4.2), 288 (60.0%) patients had payed employment, and
      292 (60.8%) patients fulfilled the clinical ACR criteria of knee OA. After 1-year
      follow-up, 236 (49.2%) patients reported persisting knee complaints, and 84
      (17.5%) reported an increase of disability. There was no association of
      fulfilling the clinical ACR criteria of knee OA at baseline with persisting knee
      complaints [odds ratio (OR) 1.15; 95% Confidence Interval (CI) 0.80; 1.67] or
      increase of disability (OR 1.05; 95% CI 0.43; 2.58) at follow-up. CONCLUSION: The
      clinical ACR classification criteria of knee OA have no prognostic value for
      predicting persisting knee complaints or an increase of disability at 1-year of
      follow-up in adult patients with non-traumatic knee complaints in GP.

PMID- 19410036
TI  - Bimanual coordination in natural orifice transluminal endoscopic surgery:
      comparing the conventional dual-channel endoscope, the R-Scope, and a novel
      direct-drive system.
AB  - BACKGROUND: The devices used for natural orifice transluminal endoscopic surgery
      procedures are endoscopes or inspired by endoscopic design, which makes it
      difficult to accomplish bimanual coordination. OBJECTIVE: We evaluated 3
      operating systems in simulated natural orifice transluminal endoscopic surgery
      procedures requiring complex bimanual coordination. DESIGN: Operators were
      required to perform an identical bimanual task by using 3 operating systems: a
      dual-channel endoscope (DCE); the R-Scope, which has 2 elevators for independent
      movement of endoscopic instruments; and the Direct Drive Endoscopic System
      (DDES), which allows separation of instruments and vision, emulating more of a
      laparoscopic surgery paradigm. SETTING: A bench-top simulation was used. Twelve
      teams were recruited for DCE and R-Scope testing. Twelve individuals participated
      in the DDES setup. The task included 3 steps: picking up a ring, passing it
      between endoscopic instruments, and placing it on a designated location. MAIN
      OUTCOME MEASUREMENTS: Task performance was evaluated by movement speed and
      accuracy. RESULTS: Task performance was significantly faster when using the DDES
      system (29 +/- 28 seconds) compared with the other operating systems (DCE: 140 +/
      55 seconds, R-Scope: 160 +/- 71 seconds; P < .001). The difference between the
      DCE and the R-Scope was not significant (P = .370). CONCLUSION: Designs that
      separate vision and motion have more degrees of freedom at the tip of the
      instruments, and an ergonomic user interface provides benefits for bimanual
      performance compared with more traditional endoscopic designs. With the DDES, a
      single operator can perform complex endoscopic tasks faster than 2 operators with
      a DCE or R-Scope.

PMID- 19410035
TI  - Does glyceryl nitrate prevent post-ERCP pancreatitis? A prospective, randomized,
      double-blind, placebo-controlled multicenter trial.
AB  - OBJECTIVE: Acute pancreatitis is the most dreaded complication of ERCP. Two
      studies have shown a significant effect of glyceryl nitrate (GN) in preventing
      post-ERCP pancreatitis (PEP). We wanted to evaluate this promising effect in a
      larger study with a realistically precalculated incidence of PEP.
      DESIGN/PATIENTS: A randomized, double-blind, placebo-controlled multicenter study
      including patients from 14 European centers was performed. A total of 820
      patients were entered; 806 were randomized. INTERVENTION: The active drug was
      transdermal GN (Discotrine/Minitran, 3M Pharma) 15 mg/24 hours; placebo (PL) was
      an identical-looking patch applied before ERCP. A total of 401 patients received
      GN; 405 received PL. RESULTS: Forty-seven patients had PEP (5.8%), 18 (4.5%) in
      the GN group and 29 (7.1%) in the PL group. The relative risk reduction of PEP in
      the GN group of 36% (95% CI, 11%-65%) compared with the PL group was not
      statistically significant (P = .11). Thirteen had mild pancreatitis (4 in the GN
      group, 9 in the PL group), 26 had moderate pancreatitis (9 in the GN group, 17 in
      the PL group), and 8 had severe pancreatitis (5 in the GN group, 3 in the PL
      group). Headache (P < .001) and hypotension (P = .006) were more common in the GN
      group. Significant variables predictive of PEP were not having biliary stones
      extracted; hypotension after ERCP; morphine, propofol, glucagon, and general
      anesthesia during the procedure; or no sufentanil during the procedure.
      CONCLUSIONS: The trial showed no statistically significant preventive effect of
      GN on PEP. Because of a considerable risk of a type II error, an effect of GN may
      have been overlooked. (ClinicalTrials.gov ID: NCT00121901.).

PMID- 19410037
TI  - Endoscopic hemostatic devices.

PMID- 19410038
TI  - Endoscopic retrieval devices.

PMID- 19410039
TI  - It takes two to tango: dance steps for diagnosing Barrett's esophagus.

PMID- 19410041
TI  - EUS for pancreatic endocrine tumors: do we need to know our pancreatic endocrine
      tumor's DNA?

PMID- 19410040
TI  - Diagnosis and management of GI stromal tumors by EUS-FNA: a survey of opinions
      and practices of endosonographers.
AB  - BACKGROUND: There is no consensus regarding the best management strategy for
      diagnosing and treating GI stromal tumors (GISTs). OBJECTIVE: Our purpose was to
      examine the practice patterns of endosonographers in diagnosing and managing
      GISTs, particularly features of GISTs suggestive of malignancy, features that
      prompt surgical referral, and surveillance patterns. DESIGN: An invitation to
      complete an online survey was e-mailed to all 413 members of the American Society
      for Gastrointestinal Endoscopy EUS Special Interest Group. RESULTS: A total of
      134 (32%) members responded; 59% of respondents use EUS features combined with
      FNA findings to diagnose GIST, and 89% consider a c-kit-positive stain on FNA
      most suggestive of GIST. However, 60% would diagnose GIST when cytologic samples
      are insufficient for diagnosis, and 40% would diagnose GIST if cytologic samples
      are sufficient but c-kit is negative. A total of 92% use size as the main
      criterion to distinguish benign from malignant GISTs, and 90% refer lesions >5 cm
      for surgery. For lesions not resected, 70% survey annually, 19% less than
      annually, 10% more than annually, and 1% do not survey. LIMITATIONS: The opinions
      of the respondents do not necessarily reflect the opinions and practices of
      endosonographers nationwide. There are inherent limitations to an online multiple
      choice survey, including low response rates. CONCLUSIONS: There are substantial
      practice variations in diagnosing, resecting, and surveying GISTs. A majority of
      our survey respondents have made the diagnosis of GIST without FNA confirmation.
      Size >5 cm is the feature used most to predict malignancy and to prompt surgical
      referral. Surveillance practices for unresected GISTs are variable. Evidence is
      needed to establish practice guidelines in this area.

PMID- 19410042
TI  - PANDA cyst-fluid analysis: eats, shoots and leaves?

PMID- 19410043
TI  - Levitra for sphincter of Oddi dysfunction? Are you kidding?

PMID- 19410044
TI  - The risks of GI endoscopy.

PMID- 19410045
TI  - Transluminal endosurgery: novel use of endoscopic tacks for the closure of access
      sites in natural orifice transluminal endoscopic surgery (with videos).
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is a novel
      and potentially less-invasive alternative to laparoscopic surgery. Successful
      reproducible secure closure of the transluminal access site represents one of the
      largest obstacles in the evolution of this discipline. AIM: To study the
      feasibility and efficacy of a novel transluminal closure device in a live porcine
      model. DESIGN: Experimental endoscopic study of transgastric incision and closure
      with a novel device in a porcine survival model. Six survival experiments were
      conducted on Yorkshire pigs that weighed 22 to 25 kg. INTERVENTIONS: After
      general anesthesia was administered, a therapeutic endoscope was inserted into
      the stomach. Two gastrotomies were made in each pig by using a needle-knife with
      blended current, a guidewire, and an 18-mm through-the-scope dilating balloon.
      The peritoneum was easily accessed in all pigs without complications. One
      gastrotomy was closed with T-tag fasteners and the other one with endoscopic
      tacks. Two different closure methods were used with the tacks: the anchor-and
      loop technique (ALT) and the serosa-to-serosa closure (SSC). All closures were
      immediately completely sealed, with no carbon dioxide (CO(2)) leak detected at 25
      cm of water pressure. After recovery from anesthesia, all the animals resumed
      feeding and returned to preprocedure activities on the same day as the procedure.
      The animals were monitored daily for signs of peritonitis and sepsis. Preplanned
      euthanasia of the animals was performed after 7 to 14 days. The peritoneal cavity
      was studied at necropsy for evidence of wound dehiscence, abscess formation, and
      gross adhesions. MAIN OUTCOME MEASUREMENTS: Full-thickness healing of the gastric
      wall incisions without intraperitoneal complications on postmortem examination.
      RESULTS: All animals survived without complications. Transgastric closure was
      successful in all the animals by using both study techniques (ALT and SSC) and
      the T-tag closure. The deployment device performed well, and accurate closure was
      rapid and reproducible. CONCLUSIONS: This prototype closure device holds promise
      in solving some of the problems of closure for transluminal access for NOTES.
      Both the ALT and the SSC technique hold promise for threadless closure and for
      simplifying endoscopic techniques. The SSC technique holds promise to maintain
      surgical principles of serosa-to-serosa apposition. Further studies are
      recommended before in vivo human use.

PMID- 19410046
TI  - Unusual foreign bodies retrieved from the colon.

PMID- 19410047
TI  - A case of duodenal Entamoeba histolytica.

PMID- 19410048
TI  - Treatment of Schatzki's ring.

PMID- 19410049
TI  - Caustic ingestion in children: is endoscopy always indicated? A perspective from
      a Sierra Leone experience.

PMID- 19410051
TI  - Clinical manifestations and management of buried bumper syndrome in patients with
      percutaneous endoscopic gastrostomy.

PMID- 19410053
TI  - Endoscopic band ligation for the treatment of gastric antral vascular ectasia.

PMID- 19410054
TI  - Snare coagulation for gastric antral vascular ectasia ablation.

PMID- 19410055
TI  - Flexible transgastric peritoneoscopy and liver biopsy.

PMID- 19410057
TI  - How to avoid unnecessary laparotomies in Mirizzi syndrome?

PMID- 19410058
TI  - The clinical significance of juxtapapillary duodenal diverticula identified at
      ERCP.

PMID- 19410059
TI  - Biliary microlithiasis.

PMID- 19410061
TI  - Capsule endoscopy for obscure GI bleeding.

PMID- 19410063
TI  - Osteonecrosis associated with short-term oral administration of bisphosphonate.
AB  - Orally administered bisphosphonates are generally considered a first-line
      medication for treatment of osteoporosis. As a side effect of bisphosphonates,
      osteonecrosis of the jaws (ONJ) has been reported worldwide. Most reports of
      osteonecrosis are attributed to the use of bisphosphonates administered
      intravenously for the treatment of bone disorders such as multiple myeloma.
      However, osteonecrosis has also been diagnosed in patients receiving oral
      bisphosphonates. The management of a patient with spontaneous removable partial
      denture prosthesis-related ONJ associated with short-term oral administration of
      bisphosphonate is described.

PMID- 19410064
TI  - Randomized controlled trial comparing a variable-thread novel tapered and a
      standard tapered implant: interim one-year results.
AB  - STATEMENT OF PROBLEM: A tapered implant with continuously changing threads
      purported to provide stable tissue support and allow immediate function has been
      developed. Treatment success and stabilization of supporting tissues over time
      require documentation. PURPOSE: The purpose of this prospective, randomized,
      controlled, multicenter study was to evaluate changes in bone level and soft
      tissue behavior between the novel implant (NobelActive/NA) and a standard tapered
      implant (NobelReplace Tapered Groovy/NR) with regard to immediate function.
      MATERIAL AND METHODS: A total of 177 patients randomly allocated to 3 treatment
      groups (2 different test implant groups: NA Internal (n=117; internal connection)
      and External (n=82), and 1 standard treatment group, NR (n=126)) received 325
      implants. Implants were placed into healed sites, and all but 6 implants were
      immediately nonocclusally loaded. Clinical and radiographic evaluations of
      treatment success, crestal bone levels, and soft tissue changes were performed at
      the time of placement and after 3, 6, and 12 months. Log-Rank test was used to
      analyze the differences in survival rate. Marginal bone level was compared using
      the Kruskal-Wallis test and Mann-Whitney U-test (alpha=.05). RESULTS: One-year
      cumulative survival rates were comparable (96.6% for NA Internal; 96.3% for NA
      External; 97.6% for NR; P=.852; Log-Rank). Mean (SD) change in bone level was 
      0.95 mm (1.37) for NA Internal, -0.64 mm (0.97) for NA External, and -0.63 mm
      (1.18) for NR (P=.589; Kruskal-Wallis). Stable soft tissues and significantly
      increased papilla scores (P<.001; Wilcoxon signed-rank) were observed for all
      implant types. CONCLUSIONS: The novel implants showed high survival rates as well
      as stable bone and soft tissue levels after 1 year, and may be recommended for
      clinical use, even under immediate function.

PMID- 19410066
TI  - In vitro comparison of the cutting efficiency and temperature production of ten
      different rotary cutting instruments. Part II: electric handpiece and comparison
      with turbine.
AB  - STATEMENT OF PROBLEM: The cutting behavior of dental rotary cutting instruments
      is influenced by the handpiece used. While the turbine handpiece has been
      extensively tested in previous studies, limited published information exists on
      the use of rotary cutting instruments with the electric handpiece system and on
      possible interactions between rotary cutting instruments and handpiece type.
      PURPOSE: The purpose of this study was to examine the cutting performance of a
      wide selection of rotary cutting instruments tested with the electric handpiece
      and compare the results with those of the air-turbine handpiece (Part I),
      identifying possible interactions between handpiece type and rotary cutting
      instruments. MATERIAL AND METHODS: Ten groups of rotary cutting instruments
      (n=30) designed for tooth preparation were selected: 9 diamond (7 multi-use, 2
      disposable) and 1 carbide. Macor blocks (n=75) were used as a substrate, and 4
      cuts were made on each specimen, using a new rotary cutting instrument each time,
      for a total of 300 cuts. The cuts were performed with an electric handpiece
      (Intramatic Lux K200), with the same methods used in the Part I study. To
      qualitatively evaluate the rotary cutting instrument surface characteristics, 1
      specimen from each group was examined 3 times with a scanning electron microscope
      (SEM): before use, then after use, but before being cleaned and sterilized, and
      finally, after ultrasonic cleaning. To compare rotary cutting instrument
      performance between the turbine and electric handpieces, the data were analyzed
      using 2-way ANOVA to study the main effects of the group of rotary cutting
      instruments, handpieces, and their interaction. For analysis of the significant
      main effect, 1-way ANOVA and Tukey's Studentized Range test were used
      (alpha=.05). RESULTS: Compared to the baseline temperature, all rotary cutting
      instruments showed a reduction of the temperature in the simulated pulp chamber
      when tested with the electric handpiece. The Great White Ultra (carbide bur)
      showed the highest rate of advancement (0.17 mm/s) and lowest applied load
      (108.35 g). Considering all rotary cutting instruments as a single group, the
      electric handpiece showed mean lower temperature (26.68 degrees C), higher rate
      of advancement (0.12 mm/s), and higher load (124.53 g) than the air-turbine
      handpiece (28.37 degrees C, 0.11 mm/s, and 121.7 g, respectively). Considering
      each single group of rotary cutting instruments, significant differences were
      found for the electric or air-turbine handpiece. CONCLUSIONS: The tested carbide
      bur showed greater cutting efficiency than the tested diamond rotary cutting
      instruments when used with the electric handpiece. The electric handpiece showed
      a higher cutting efficiency than the turbine, especially when used with the
      carbide bur, probably due to its greater torque.

PMID- 19410065
TI  - Correlations between physical properties of jawbone and dental implant initial
      stability.
AB  - STATEMENT OF PROBLEM: There is confusion in the literature about how physical
      properties of bone vary between maxillary and mandibular regions and which
      physical properties affect initial implant stability. PURPOSE: The purpose of
      this study was to determine correlations between physical properties of bone and
      initial implant stability, and to determine how physical properties and initial
      stability vary among regions of jawbone. MATERIAL AND METHODS: Four pairs of
      edentulous maxillae and mandibles were retrieved from fresh human cadavers. Six
      implants per pair were placed in different anatomical regions (maxillary
      anterior, right and left maxillary posterior, mandibular anterior, right and left
      mandibular posterior). Immediately after surgery, initial implant stability was
      measured with a resonance frequency device and a tapping device. Implant
      surgeries and initial stability measurements were performed within 72 hours of
      death. Elastic modulus (EM) and hardness were measured using nano-indentation.
      Composite apparent density (cAD) was measured using Archimedes' principle. Bone
      implant contact percentage and cortical bone thickness were recorded
      histomorphometrically. Mixed linear models and univariate-correlation analyses
      were used (alpha=.05). RESULTS: Generally, mandibular bone had higher initial
      implant stability and physical properties than maxillary bone. Initial implant
      stability was higher in the anterior region than in the posterior. EM was higher
      in the posterior region than in the anterior; the reverse was true for cAD.
      CONCLUSIONS: Of the properties evaluated, cAD had the highest correlation with
      initial implant stability (r=0.82). Both physical properties of bone and initial
      implant stability differed between regions of jawbone.

PMID- 19410067
TI  - Accuracy of a reformulated fast-set vinyl polysiloxane impression material using
      dual-arch trays.
AB  - STATEMENT OF PROBLEM: A common technique used for making crown impressions
      involves use of a vinyl polysiloxane impression material in combination with a
      dual-arch tray. A leading dental manufacturer has reformulated its vinyl
      polysiloxane (VPS) impression line, but the accuracy of the new material has not
      been verified. PURPOSE: The purpose of this study was to assess the accuracy of
      reformulated VPS impression materials using the single-step dual-arch impression
      technique. MATERIAL AND METHODS: Dual-arch impressions were made on a typodont
      containing a master stainless steel standard crown preparation die, from which
      gypsum working dies were formed, recovered, and measured. The impression
      materials evaluated were Imprint 3 Penta Putty with Quick Step Regular Body (IP
      0); Imprint 3 Penta Quick Step Heavy Body with Quick Step Light Body (IP-1);
      Aquasil Ultra Rigid Fast Set with LV Fast Set (AQ-1); and Aquasil Ultra Heavy
      Fast Set with XLV Fast Set (AQ-2) (n=10). All impressions were disinfected with
      CaviCide spray for 10 minutes prior to pouring with type IV gypsum. Buccolingual
      (BL), mesiodistal (MD), and occlusogingival (OG) dimensions were measured and
      compared to the master die using an optical measuring microscope. Linear
      dimensional change was also assessed for IP-0 and AQ-1 at 1 and 24 hours based on
      ANSI/ADA Specification No. 19. Single-factor ANOVA with Dunnett's T3 multiple
      comparisons was used to compare BL, MD, and OG changes, with hypothesis testing
      at alpha=.05. A repeated-measures ANOVA was used to compare linear dimensional
      changes. RESULTS: There were statistical differences among the 4 impression
      systems for 3 of 4 dimensions of the master die. IP-0 working dies were
      significantly larger in MD and OG-L dimensions but significantly smaller in the
      BL dimension. IP-1 working dies were significantly smaller in the BL dimension
      compared to the master die. With the exception of IP-0, differences detected were
      small and clinically insignificant. No significant differences were observed for
      linear dimensional change. CONCLUSIONS: The single-step dual-arch impression
      technique produced working dies that were smaller in 3 of the 4 dimensions
      measured and may require additional die relief to achieve appropriate fit of cast
      restorations. Overall accuracy was acceptable for all impression groups with the
      exception of IP-0.

PMID- 19410068
TI  - The influence of antagonistic surface roughness on the wear of human enamel and
      nanofilled composite resin artificial teeth.
AB  - STATEMENT OF PROBLEM: Depending on the applied finishing technique, ceramics may
      have different values of surface roughness; therefore, their abrasive effect on
      antagonists may vary. However, different materials may be affected differently by
      the surface roughness of ceramics. PURPOSE: The purpose of the present study was
      to evaluate and correlate the wear of human enamel and nanofilled composite resin
      teeth with the surface roughness of the antagonistic ceramic after simulated
      mastication. MATERIAL AND METHODS: Three groups of 8 human teeth and 3 groups of
      8 nanofilled composite resin teeth were tested against 3 sets of 16 zirconia
      ceramic balls with different average surface roughness values. Each group was
      loaded for 300,000 cycles in a mastication simulator. Wear resistance was
      analyzed by measuring volume and vertical substance lost, determined with a laser
      scanner. Data were statistically analyzed using 2-way ANOVA. The Pearson
      correlation test was used to determine whether there was a relationship between
      the antagonistic surface roughness and the degree to which the materials had
      worn. RESULTS: An increase in the antagonistic surface roughness significantly
      increased the wear of composite resin and human enamel. The effect of the
      antagonistic surface roughness on the wear was significant (P<.001). The
      correlation between the volume loss and antagonistic surface roughness was
      significant (r=0.667, P<.001). CONCLUSIONS: Nanofilled composite resin and human
      enamel exhibited different amounts of wear. In general, human enamel showed less
      wear than nanofilled composite resin. Surface roughness of the antagonistic
      ceramic influenced the wear of human enamel more than it affected the wear of
      composite resin.

PMID- 19410069
TI  - Remount cast fabrication for occlusal equilibration against artificial denture
      teeth.

PMID- 19410070
TI  - Nonsurgical root canal therapy of large cyst-like inflammatory periapical lesions
      and inflammatory apical cysts.
AB  - It is a general belief that large cyst-like periapical lesions and apical true
      cysts caused by root canal infection are less likely to heal after nonsurgical
      root canal therapy. Nevertheless, there is no direct evidence to support this
      assumption. A large cyst-like periapical lesion or an apical true cyst is formed
      within an area of apical periodontitis and cannot form by itself. Therefore, both
      large cyst-like periapical lesions and apical true cysts are of inflammatory and
      not of neoplastic origin. Apical periodontitis lesions, regardless of whether
      they are granulomas, abscesses, or cysts, fail to heal after nonsurgical root
      canal therapy for the same reason, intraradicular and/or extraradicular
      infection. If the microbial etiology of large cyst-like periapical lesions and
      inflammatory apical true cysts in the root canal is removed by nonsurgical root
      canal therapy, the lesions might regress by the mechanism of apoptosis in a
      manner similar to the resolution of inflammatory apical pocket cysts. To achieve
      satisfactory periapical wound healing, surgical removal of an apical true cyst
      must include elimination of root canal infection.

PMID- 19410071
TI  - External cervical resorption: a review.
AB  - External cervical resorption (ECR) is the loss of dental hard tissue as a result
      of odontoclastic action; it usually begins on the cervical region of the root
      surface of the teeth. The etiology, predisposing factors, diagnosis, and
      management of ECR are reviewed. Effective management and appropriate treatment
      can only be carried out if the true nature and exact location of the ECR lesion
      are known. The role of cone beam computed tomography as a diagnostic adjunct for
      the management of ECR is also reviewed.

PMID- 19410073
TI  - The effect of different vasoconstrictors and local anesthetic solutions on
      substance P expression in human dental pulp.
AB  - The purpose of this study was to quantify the effect of the infiltration
      injection of different vasoconstrictor and anesthetic solutions on substance P
      (SP) expression in healthy human dental pulp. Thirty pulp samples were obtained
      from healthy upper premolars in which extraction was indicated for orthodontic
      reasons and were randomly assigned into three groups of 10 samples each: 2%
      lidocaine with 1:80,000 epinephrine (Lido group), 3% Prilocaine with 1:200000
      felypressin (Prilo group); and 4% Prilocaine without vasoconstrictor (Prilo-no-VC
      group). All teeth were extracted 10 minutes after anesthetic application. Pulp
      samples were processed and SP was measured by radioimmunoassay. SP expression for
      the Lido, Prilo, and Prilo-no-VC groups were 616.49, 663.76, and 760.79 pmol/mg
      pulp tissue, respectively. Analysis of variance showed statistically significant
      differences between groups (p = 0.001). Tukey Honestly Significant Difference
      (HSD) post hoc tests showed significant statistical differences between the Prilo
      no-VC group and the Lido group (p < 0.01) and between the Prilo-no-VC group and
      the Prilo group (p < 0.05). It can be concluded that infiltration injection of
      local anesthetics with vasoconstrictor attenuate SP expression in human dental
      pulp.

PMID- 19410072
TI  - Association between chronic dental infection and acute myocardial infarction.
AB  - INTRODUCTION: In patients with cardiovascular diseases several risk factors such
      as high blood pressure, diabetes, smoking and drinking habits, genetic
      disposition, and chronic inflammation must be considered. The aim of this study
      was to investigate whether there is a correlation between dental origin
      infections and the presence of an acute myocardial infarction (AMI). METHODS: A
      total of 125 patients who had experienced a myocardial infarction and 125 healthy
      individuals were included in this study. The oral examination was carried out
      following the consent of the ethics committee and the National Board for
      Radiation Protection and included the number of teeth, endodontically treated
      teeth, periodontal screening index (PSI), clinical attachment level, and
      radiographic apical lesions (radiograph examination). The medical examination
      included, among others, blood glucose level, C-reactive protein (CRP) serum
      levels, and leukocyte number. RESULTS: The study demonstrated that patients with
      AMI exhibited an unfavorable dental state of health. After statistical adjustment
      for age, gender, and smoking, they exhibited a significantly higher number of
      missing teeth (P = .001), less teeth with root canal fillings (P = .0015), a
      higher number of radiologic apical lesions (P = .001), and a higher PSI value (P
      = .001) compared with individuals without myocardial infarction. The medical data
      showed a nonsignificant correlation between CRP and the number of radiologic
      apical lesions. CONCLUSIONS: This study presents evidence that patients who have
      experienced myocardial infarction also exhibit an unfavorable dental state of
      health in comparison to healthy patients and suggests an association between
      chronic oral infections and myocardial infarction.

PMID- 19410074
TI  - Histology of periapical lesions obtained during apical surgery.
AB  - The aim of this was to evaluate the histology of periapical lesions in teeth
      treated with periapical surgery. After root-end resection, the root tip was
      removed together with the periapical pathological tissue. Histologic sectioning
      was performed on calcified specimens embedded in methylmethacrylate (MMA) and on
      demineralized specimens embedded in LR White (Fluka, Buchs, Switzerland). The
      samples were evaluated with light and transmission electron microscopy (TEM). The
      histologic findings were classified into periapical abscesses, granulomas, or
      cystic lesions (true or pocket cysts). The final material comprised 70%
      granulomas, 23% cysts and 5% abscesses, 1% scar tissues, and 1% keratocysts. Six
      of 125 samples could not be used. The cystic lesions could not be subdivided into
      pocket or true cysts. All cysts had an epithelium-lined cavity, two of them with
      cilia-lined epithelium. These results show the high incidence of periapical
      granulomas among periapical lesions obtained during apical surgery. Periapical
      abscesses were a rare occasion. The histologic findings from samples obtained
      during apical surgery may differ from findings obtained by teeth extractions. A
      determination between pocket and true apical cysts is hardly possible when
      collecting samples by apical surgery.

PMID- 19410075
TI  - The morphologic characteristics of the distolingual roots of mandibular first
      molars in a Taiwanese population.
AB  - INTRODUCTION: The prevalence of extra distolingual (DL) roots in mandibular first
      molars in Chinese population is about 20%. The purpose of this study was to
      evaluate the difference of root length and root curvatures between distobuccal
      (DB) and DL roots of three-rooted mandibular first molars in a Taiwanese
      (Chinese) population. METHODS: Of the 293 extracted mandibular first molars, DL
      roots were present in 29 (9.9%) teeth. Excluding teeth with fractured DB or DL
      roots, 21 mandibular first molars were further investigated. DB and DL root
      lengths were measured from the lower level of furcation at the distal surface to
      the root apex. The curvature of the DL root was measured on mesial-distal and
      buccal-lingual radiographs by Schneider's technique. RESULTS: The DL roots were
      significantly (p < 0.001) shorter than the DB roots with an average of 1.48 +/-
      0.81 mm. Most DL roots had a greater curvature in a buccal-lingual orientation
      (36.35 degrees +/- 9.38 degrees ) than a mesial-distal orientation (9.24 degrees
      +/- 6.10 degrees ) and 28.57% of the curved DL roots had the curvature at the
      apical one third (p < 0.001). CONCLUSION: The results of this study verified the
      characteristics of shorter root length and severe buccal-lingual inclination of
      DL roots in three-rooted mandibular first molars.

PMID- 19410077
TI  - Root canal morphology of permanent maxillary teeth in the Han nationality in
      Chinese Guanzhong area: a new modified root canal staining technique.
AB  - INTRODUCTION: The purpose of this study was to investigate the canal morphology
      of 504 maxillary permanent teeth of subjects of Han nationality in Chinese
      Guanzhong area. METHODS: Maxillary permanent teeth were randomly collected in
      Guanzhong area. After regular preparation, the teeth were immersed into ink
      without preparing access cavities and then put into hyperbaric oxygen chamber
      (0.6 Mpa) for 2 hours to let the ink penetrate into root canal from apical
      foramen, apical deltas and foramen of lateral canals under stable positive
      pressure. After demineralization and clearing, the following observations were
      made: (1) number of root canals, (2) root canal configuration by using Vertucci's
      classification, (3) presence of lateral canals, and (4) frequency of apical
      deltas. RESULTS: All the teeth were well-stained, and the fine details were well
      revealed. Apical deltas (12.2%-83.3%) and lateral canals (13.7%-68.8%) could be
      frequently found in all types of maxillary teeth. Most of central incisors
      (95.8%), lateral incisors (91.4%), and canines (75.4%) displayed type I canal
      configuration, whereas most of first premolars (87.3%) and second premolars
      (72.3%) possessed 2 canals with type II, IV, or VI canal configuration. The
      majority of distobuccal roots and palatal roots of first molars (88.9%, 97.8%),
      second molars (92.0%, 94.0%), and third molars (87.5%, 91.6%) possessed type I
      canal configuration. The prevalence of mesiobuccal roots with type I
      configuration was 66.7% in maxillary first molars, 82% in second molars, and
      62.5% in third molars. CONCLUSIONS: The modified technique of canal staining can
      effectively reveal detailed root canal system. The canal configuration of
      maxillary teeth in subjects of Han nationality in Chinese Guanzhong area is
      consistent with previous reports in other races.

PMID- 19410076
TI  - Update on imbalanced distribution of endodontists: 1995-2006.
AB  - INTRODUCTION: Past studies on the number of endodontists in the United States
      indicated an imbalanced distribution of private practice endodontic practitioners
      in most regions, states, counties, and zip code areas of the country. The
      availability of more recent studies by the American Dental Association (ADA)
      provides an opportunity to follow up on these previous studies. METHODS: The 2006
      and past ADA surveys on the Distribution of Dentists in the United States,
      Advanced Dental Education, and Dental Practice were used to evaluate the number
      of graduates from advanced education programs in endodontics, the changing number
      and distribution of endodontists, full-time and part-time work patterns, and the
      income of private practicing endodontists. RESULTS: A gradual increase in the
      number of graduates from advanced education programs in endodontics is reflected
      in a continuing increase in the overall number of private practicing
      endodontists, but with ongoing differences in endodontists-to-population ratios
      at the regional and state levels. CONCLUSION: The findings follow previous study
      results confirming the increasing numbers of endodontists and continuing
      differences in the endodontists-to-population ratios at both the regional and
      state levels. Concerns about the distribution of endodontists in the future need
      to be considered in terms of evolving dental disease patterns, changing demands
      for services, evolving third-party mechanisms, and the increased number of female
      practitioners (with fewer reported working hours than their male counterparts).

PMID- 19410078
TI  - Simvastatin as a novel strategy to alleviate periapical lesions.
AB  - Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are widely used
      cholesterol-lowering agents that also possess anti-inflammatory activities.
      Cysteine-rich 61 (Cyr61) and CCL2 are potential osteolytic mediators in
      inflammatory bone diseases. The study assessed the effect of simvastatin on tumor
      necrosis factor alpha (TNF- alpha)-induced synthesis of Cyr61 and CCL2 in MG-63
      human osteoblastic cells. The therapeutic effect of simvastatin on rat apical
      periodontitis was also examined. The synthesis of Cyr61 in MG-63 was assessed by
      Western analysis. Expression of CCL2 was examined by an enzyme-linked
      immunosorbent assay. The effect of simvastatin on induced rat periapical lesion
      was examined radiographically and immunohistochemically. Western blot showed that
      TNF-alpha stimulated Cyr61 synthesis in MG-63, whereas simvastatin attenuated
      this effect in a dose-dependent manner. Simvastatin also reduced the levels of
      TNF-alpha-induced CCL2, and exogenous Cyr61 restored the inhibitory effects.
      Radiography and histopathology revealed that the administration of simvastatin
      markedly diminished the severity of induced rat periapical lesions. The numbers
      of Cyr61-synthesizing osteoblasts and CD-68-positive macrophages were also
      decreased. Simvastatin suppresses the progression of apical periodontitis,
      possibly by diminishing Cyr61 expression in osteoblasts and, subsequently,
      macrophage chemotaxis into the lesions.

PMID- 19410079
TI  - Effect of intracanal corticosteroids on healing of replanted dog teeth after
      extended dry times.
AB  - This study investigated the effect of potent intracanal corticosteroids on
      periodontal healing of replanted avulsed teeth and evaluated the systemic
      absorption of these corticosteroids. Sixty-seven extracted dog premolar roots
      were randomly assigned to one of the following groups: groups 1-3 filled with
      gutta-percha and replanted immediately and after 40 and 60 minutes, respectively;
      groups 4 and 5 filled with 0.05% clobetasol; and groups 6 and 7 filled with 0.05
      % fluocinonide. Groups 4 and 6 were replanted after 40 minutes and groups 5 and 7
      after 60 minutes. After 4 months, roots were evaluated histologically for signs
      of periodontal healing. Roots treated with clobetasol and fluocinonide healed
      more favorably than roots filled with gutta-percha and were different from each
      other at 60 minutes. No change in the systemic corticosteroid blood concentration
      was observed in any group. Corticosteroids were efficacious in the beagle model
      as intracanal medicaments for promoting favorable postavulsion periodontal
      healing.

PMID- 19410080
TI  - Ozonated water improves lipopolysaccharide-induced responses of an odontoblast
      like cell line.
AB  - INTRODUCTION: It is important to develop an antimicrobial agent without any
      damage on dental pulp. In the present study, we examined whether pretreatment of
      bacterial lipopolysaccharides (LPS) with ozonated water (O(3)aq) improves LPS
      induced responses of rat odontoblastic cell line, KN-3. METHODS: After the
      pretreatment of LPS with O(3)aq, effects of LPS and O(3)aq-treated LPS on cell
      viability; calcification ability; expression of cyclooxygenase 2 (COX-2),
      interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha); and activation
      of p38 of KN-3 cells were examined. RESULTS: The formation of mineralized nodules
      by KN-3 cells was suppressed by LPS, whereas that suppression was inhibited by
      the pretreatment of LPS with ozonated water. We also found that LPS-induced
      expression of COX-2, IL-6, and TNF-alpha and p38 activation were markedly
      suppressed when LPS was pretreated with ozonated water. Furthermore, expression
      of COX-2, IL-6, and TNF-alpha by LPS were mainly induced through p38 activation.
      CONCLUSION: These results suggest that odontoblastic cells exhibit inflammatory
      responses against LPS and that ozonated water has the ability to improve LPS
      induced inflammatory responses and suppression of odontoblastic properties of KN
      3 cells through direct inhibition of LPS.

PMID- 19410081
TI  - Isolation and characterization of human dental pulp stem/stromal cells from
      nonextracted crown-fractured teeth requiring root canal therapy.
AB  - INTRODUCTION: Human dental pulp stem/stromal cells (hDPSCs) in adults are
      primarily derived from the pulp tissues of permanent third molar teeth in
      existing literatures, whereas no reports exist, to our knowledge, on deriving
      hDPSCs from a tooth without the need for surgical procedure. The aim of this
      study was to raise a novel idea to source hDPSCs from complicated crown-fractured
      teeth requiring root canal therapy. METHODS: hDPSCs were harvested from the pulp
      tissues for two complicated crown-fractured teeth requiring root canal therapy,
      retaining the teeth for subsequent prosthodontic rehabilitation, in a 41-year-old
      woman who had suffered a motorcycle accident. Pulp tissue from the left lower
      deciduous canine of a healthy 10-year-old boy (the positive control) was also
      removed because of high mobility and cultured for hDPSCs. RESULTS: The hDPSCs
      derived from the two complicated crown-fractured teeth and the deciduous tooth
      were able to differentiate into adipogenic, chondrogenic, and osteogenic lineages
      and also expressed stem cells markers and differentiation markers, which
      indicated their stem cell origin and differentiation capability. In addition,
      hDPSCs from both the complicated crown-fractured teeth and the deciduous tooth
      showed high expression for bone marrow stem cell markers including CD29, CD90,
      and CD105 and exhibited very low expression of markers specific for hematopoietic
      cells such as CD14, CD34, and CD45. CONCLUSIONS: This report describes the
      successful isolation and characterization of hDPSCs from the pulp tissue of
      complicated crown-fractured teeth without tooth extraction. Therefore, pulp
      exposed in complicated crown-fractured teeth might represent a valuable source of
      personal hDPSCs.

PMID- 19410082
TI  - Comparison of calcium and silicate cement and mineral trioxide aggregate biologic
      effects and bone markers expression in MG63 cells.
AB  - Bone cell (MG63) biocompatibility and bone marker expression were compared after
      calcium and silicate base cement (CS) and mineral trioxide aggregate (MTA)
      treatment. X-ray diffraction was used to identify material surface structure, and
      tetrazolium bromide colorimetric assay was used to evaluate the cell viability.
      The relative mitogen activation protein kinase expression was compared with
      Western blot, and bone marker expression was evaluated with reverse transcriptase
      polymerization chain reaction. The results showed that CS and MTA are similar
      chemical structures and biocompatible with MG63 cells. CS and MTA cements showed
      good MG63 cell proliferation by high phosphor extracellular signal-regulated
      kinase expression levels. CS and MTA cements showed the evident type I collagen,
      osteocalcin, alkaline phosphatase, bone sialoprotein, and osteopontin expression.
      Both MTA and CS cements are biocompatible and appear to have osetoconduction
      effects on bone cells.

PMID- 19410083
TI  - Determination of matrix metalloproteinases in human radicular dentin.
AB  - Matrix metalloproteinases (MMPs) are present in sound coronal dentin and may play
      a role in collagen network degradation in bonded restorations. We investigated
      whether these enzymes can also be detected in root dentin. Crown and root
      sections of human teeth were powderized, and dentin proteins were extracted by
      using guanidine-HCl and EDTA. Extracts were analyzed by zymography and Western
      blotting for matrix metalloproteinases detection. Zymography revealed
      gelatinolytic activities in both crown and root dentin samples, corresponding to
      MMP-2 and MMP-9. MMP-2 was more evident in demineralized root dentin matrix,
      whereas MMP-9 was mostly extracted from the mineralized compartment of dentin and
      presented overall lower levels. Western blot analysis detected MMP-8 equally
      distributed in crown and root dentin. Because MMPs are also present in radicular
      dentin, their contribution to the degradation of resin-dentin bonds should be
      addressed in the development of restorative strategies for the root substrate.

PMID- 19410084
TI  - Expression of metabotropic glutamate receptor mGluR5 in human dental pulp.
AB  - Accumulating evidence indicates that the metabotropic glutamate receptor mGluR5
      is involved in the peripheral mechanisms of inflammatory nociception. To
      investigate whether mGluR5 may mediate the inflammatory pain and thermal
      hyperalgesia in the dental pulp, we examined the expression of mGluR5 and
      transient receptor potential vanilloid 1 (TRPV1) in human dental pulp by
      immunohistochemistry and electron microscopy; mGluR5-immunopositive (+) axons
      were observed in nerve bundles and branched extensively within the peripheral
      coronal pulp. Most of the mGluR5+ axons were unmyelinated. A large fraction of
      these axons (36.5%) were immunostained for TRPV1. Immunoreactivity for mGluR5 and
      TRPV1 was also observed in odontoblasts. These results support the possibility
      that the nerve fibers in the dental pulp mediate inflammatory pain and thermal
      hyperalgesia through coactivation of mGluR5 and TRPV1 and also suggest a possible
      role for odontoblasts in the transduction of nociceptive signals via mGluR5
      mediated mechanism.

PMID- 19410085
TI  - An in vitro evaluation of effect of ionizing radiotherapy on push-out strength of
      fiber posts under cyclic loading.
AB  - Ionizing radiotherapy has a deleterious effect on all vital cells and thus might
      affect the collagen fibril network of dentin and formation of hybrid layer of
      composite resins. The present study evaluated the effect of ionizing x-ray
      radiotherapy on push-out bond strength of fiber posts. Sixty mandibular premolar
      roots were divided into 4 groups: group I, control group with no irradiation,
      restored with a quartz fiber post system with cyclic loading; group II, samples
      were exposed to 60 Gy radiation dosage and than restored; group III, samples were
      restored and then irradiated; and group IV, samples were restored during
      irradiation. A push-out bond strength test was done. Radiotherapy significantly
      reduced the push-out bond strength of fiber posts. Patients undergoing ionizing
      radiotherapy might have a less than ideal prognosis of fiber posts luted with
      dual cure resin cement with total etch bonding system, if restorations are done
      after radiotherapy.

PMID- 19410086
TI  - Effectiveness of a manual glide path on the preparation of curved root canals by
      using Mtwo rotary instruments.
AB  - INTRODUCTION: Nickel-titanium rotary instruments reduce procedural errors and the
      time required to finish root canal preparation. The goal of this study was to
      evaluate the effectiveness of a manual glide path on the preparation of curved
      root canals with Mtwo rotary system. METHODS: Forty buccal root canals with
      angles of curvature between 25 to 76 degrees were randomly divided into 4 groups
      (n = 10); 2 groups were instrumented with Mtwo instruments to the full length,
      and in the other 2 groups a glide path with #08-15 K files was performed before
      instrumentation with Mtwo system. Digital double radiographic technique was used
      to determine apical transportation and the change in angle of curvature. Also
      working time was calculated. RESULTS: No statistically significant differences in
      the angle of canal curvature, apical transportation, and the working time were
      found between groups with glide path and no glide path. No significant
      differences were found when comparing the results of 3 variables between degrees
      of curvature. CONCLUSION: The use of a manual glide path before Mtwo rotary
      system did not influence the apical transportation in curved root canals.

PMID- 19410087
TI  - Effect of white mineral trioxide aggregate mixed with disodium hydrogen phosphate
      on inflammatory cells.
AB  - INTRODUCTION: The aim of this study was subjective evaluation of inflammatory
      cells subsequent to subcutaneous implantation of white mineral trioxide aggregate
      (WMTA) mixed with disodium hydrogen phosphate (Na(2)HPO(4)) in rats. METHODS:
      Forty Wistar rats were used in this study. Polyethylene tubes filled with WMTA
      mixed with Na(2)HPO(4) and WMTA alone and also empty tubes serving as control
      were implanted into subcutaneous tissue and harvested after 7, 15, 30, and 90
      days. Histologic sections were stained with hematoxylin-eosin and observed under
      a light microscope. Inflammatory reactions were categorized as 0 or none (without
      inflammatory cells), 1 or mild (inflammatory cells < 25), 2 or moderate (25-125
      inflammatory cells), and 3 or severe (more than 125 inflammatory cells).
      Statistical analyses were performed with the Kruskal-Wallis and Mann-Whitney
      tests. RESULTS: WMTA alone provoked a moderate inflammatory reaction after 7 and
      15 days, which significantly differed from WMTA mixed with Na(2)HPO(4) and the
      control group, which provoked a mild inflammatory reaction (P < .05). However,
      there were no significant differences at any period beyond 30 days. CONCLUSIONS:
      This study indicates that adding Na(2)HPO(4) to WMTA creates a more biocompatible
      material than WMTA alone.

PMID- 19410089
TI  - Enterococcus faecalis biofilms eradication by root canal irrigants.
AB  - The aim of this study was to evaluate the minimal biofilm eradication
      concentration (MBEC) of sodium hypochlorite (NaOCl), chlorhexidine (CHX), EDTA,
      and citric and phosphoric acids after 1, 5, and 10 minutes of exposure to
      biofilms of Enterococcus faecalis. The biofilms grew in the MBEC high-throughput
      device for 24 hours at 37 degrees C and were exposed to 10 serial two-fold
      dilutions of each irrigating solution. The viable cell counts were log(10)
      transformed, and a concentration of an irrigant was considered to eradicate the
      biofilms when it produced a reduction of > or = 5 logarithmic units. NaOCl was
      the most effective agent, capable of eradicating the biofilms after 1 minute at a
      concentration of 0.00625%. CHX eradicated biofilm after 5 minutes at 2%. EDTA and
      citric and phosphoric acid solutions were not effective against the biofilms at
      any concentration or time tested.

PMID- 19410088
TI  - Scanning electron micrograph and surface hardness of mineral trioxide aggregate
      in the presence of alkaline pH.
AB  - INTRODUCTION: The aim of this study was to evaluate morphologic microstructure
      and surface hardness of white mineral trioxide aggregate (WMTA) after exposure to
      a range of alkaline environments during hydration. METHODS: WMTA was mixed and
      packed into 60 glass tubes. Four groups, each containing 15 tubes, were exposed
      to pH values of 7.4, 8.4, 9.4, and 10.4, respectively, for 3 days. In 12 tubes in
      each group, Vickers surface hardness was measured after exposure to alkaline
      environments. Data were subjected to one-way analysis of variance and a post hoc
      Tukey test. Three specimens in each group were prepared to be evaluated under a
      scanning electron microscope using scattered electron (SE) and backscattered
      electron (BSE) detectors. RESULTS: The mean surface hardness values +/- standard
      deviation after exposure to pH values of 7.4, 8.4, 9.4, and 10.4 were 58.28 +/-
      8.21, 68.84 +/- 7.19, 67.32 +/- 7.22, and 59.22 +/- 9.14, respectively. The
      difference between these values was statistically significant (p = 0.000). There
      were statistically significant differences between pH values of 8.4 and 9.4 and
      pH values of 7.4 and 10.4 (p > 0.05). The SE detector revealed needle-shaped
      crystals at pH values of 7.4 and 8.4 and an amorphous microstructure at pH values
      of 9.4 and 10.4 on WMTA surface. The BSE detector showed more unhydrated
      structure and pores at pH values of 7.4 and 10.4 compared with pH values of 8.4
      and 9.4. CONCLUSIONS: Surface hardness can be influenced by different alkaline pH
      values. The BSE detector can reveal more microstructure details of WMTA in
      conjunction with the SE detector. More porosity and unhydrated structure are
      observed in WMTA exposed to pH values of 7.4 and 10.4.

PMID- 19410090
TI  - Solubility of Epiphany endodontic sealer prepared with resinous solvent.
AB  - PURPOSE: To evaluate in vitro the solubility of the Epiphany endodontic filling
      material Epiphany (Pentron Clinical Technologies, Wallingford, CT) prepared with
      its resinous solvent. METHODS: The specimens were prepared in the following
      experimental conditions: (1) GI, epiphany without photoactivation; (2) GII,
      Epiphany prepared with resinous solvent without photoactivation; (3) GIII,
      Epiphany followed by photoactivation; and (4) GIV, Epiphany prepared with
      resinous solvent followed by photoactivation. Ten specimens of each group were
      obtained from Teflon molds with 80% reduction in volume of the specimen's
      dimensions based on American National Standard Institute/American Dental
      Association (ANSI/ADA) Specification No. 57. The samples were weighted and
      immersed in distilled water for 7 days. After this period, they were removed,
      dried, and weighed again. Solubility was calculated by using samples weight loss
      (%). The immersion liquid was evaluated through atomic absorption spectrometry.
      RESULTS: The sealers without photoactivation were statistically similar (p >
      0.05) between themselves (GI = 6.93% and GII = 6.39%) and different from the
      uncured sealers, which were statistically different between themselves (p < 0.05)
      (GIII = 3.56% and GIV = 0.47%). Only the Epiphany sealer prepared with resinous
      solvent followed by photoactivation presented solubility values within ANSI/ADA
      requirements, liberating the following amounts of ions: 114.43 microg of
      Ca(2+)/mL, 2.4 microg of Mg(2+)/mL, 0.33 microg of Fe(2+)/mL, 0.11 microg of
      Zn(2+)/mL, 1.31 microg of Ni(2+)/mL, and 7.1 microg of Na(+)/mL. CONCLUSION: The
      association of resinous solvent to the Epiphany sealer followed by
      photoactivation resulted in a filling material with low solubility and expressive
      liberation of calcium ions.

PMID- 19410091
TI  - Detection of vertical root fractures in endodontically treated teeth by a cone
      beam computed tomography scan.
AB  - Our aim was to compare the accuracy of cone beam computed tomography (CBCT) scans
      and periapical radiographs (PRs) in detecting vertical root fractures (VRFs) and
      to assess the influence of root canal filling (RCF) on fracture visibility.
      Eighty teeth were endodontically prepared and divided into four groups. The teeth
      in groups A and B were artificially fractured, and teeth in groups C and D were
      not. Groups A and C were root filled. Four observers evaluated the CBCT scans and
      PR images. Sensitivity and specificity for VRF detection of CBCT were 79.4% and
      92.5% and for PR were 37.1% and 95%, respectively. The specificity of CBCT was
      reduced (p = 0.032) by the presence of RCF, but its overall accuracy was not
      influenced (p = 0.654). Both the sensitivity (p = 0.006) and overall accuracy (p
      = 0.008) of PRs were reduced by the presence of RCF. The results showed an
      overall higher accuracy for CBCT (0.86) scans than PRs (0.66) for detecting VRF.

PMID- 19410092
TI  - Outcome of root canal treatment in dogs determined by periapical radiography and
      cone-beam computed tomography scans.
AB  - The purpose of this study was to compare the favorable outcome of root canal
      treatment determined by periapical radiographs (PRs) and cone beam computed
      tomography (CBCT) scans. Ninety-six roots of dogs' teeth were used to form four
      groups (n= 24). In group 1, root canal treatments were performed in healthy
      teeth. Root canals in groups 2 through 4 were infected until apical periodontitis
      (AP) was radiographically confirmed. Roots with AP were treated by one-visit
      therapy in group 2, by two-visit therapy in group 3, and left untreated in group
      4. The radiolucent area in the PRs and the volume of CBCT-scanned periapical
      lesions were measured before and 6 months after the treatment. In groups 1, 2,
      and 3, a favorable outcome (lesions absent or reduced) was shown in 57 (79%)
      roots using PRs but only in 25 (35%) roots using CBCT scans (p = 0.0001).
      Unfavorable outcomes occurred more frequently after one-visit therapy than two
      visit therapy when determined by CBCT scans (p = 0.023).

PMID- 19410093
TI  - Atomic absorption spectrometry and scanning electron microscopy evaluation of
      concentration of calcium ions and smear layer removal with root canal chelators.
AB  - AIM: The aim of this study was to evaluate the concentration of calcium ions and
      smear layer removal by using root canal chelators according to flame atomic
      absorption spectrophotometry and scanning electron microscopy. Forty-two human
      maxillary central incisors were irrigated with 15% ethylenediaminetetraacetic
      acid (EDTA), 10% citric acid, 10% sodium citrate, apple vinegar, 5% acetic acid,
      5% malic acid, and sodium hypochlorite. The concentration of calcium ions was
      measured by using flame atomic absorption spectrometry, and smear layer removal
      was determined by scanning electron microscopy. Mean +/- standard deviation, one
      way analysis of variance, Tukey-Kramer, Kruskal-Wallis, Dunn, and kappa tests
      were used for statistical analysis. The use of 15% EDTA resulted in the greatest
      concentration of calcium ions followed by 10% citric acid; 15% EDTA and 10%
      citric acid were the most efficient solutions for removal of smear layer.

PMID- 19410094
TI  - Biomineralization ability and interaction of mineral trioxide aggregate and white
      portland cement with dentin in a phosphate-containing fluid.
AB  - INTRODUCTION: Mineral trioxide aggregate (MTA) has been shown to be bioactive
      because of its ability to produce biologically compatible carbonated apatite.
      This study analyzed the interaction of MTA and white Portland cement with dentin
      after immersion in phosphate-buffered saline (PBS). METHODS: Dentin disks with
      standardized cavities were filled with ProRoot MTA, MTA Branco, MTA BIO, white
      Portland cement + 20% bismuth oxide (PC1), or PC1 + 10% of calcium chloride (PC2)
      and immersed in 15 mL of PBS for 2 months. The precipitates were weighed and
      analyzed by scanning electron microscopy (SEM) and x-ray diffraction. The calcium
      ion release and pH of the solutions were monitored at 5, 15, 25, and 35 days. The
      samples were processed for SEM observations. Data were analyzed by using analysis
      of variance or Kruskall-Wallis tests. RESULTS: Our findings revealed the presence
      of amorphous calcium phosphate precipitates with different morphologies. The
      apatite formed by the cement-PBS system was deposited within collagen fibrils,
      promoting controlled mineral nucleation on dentin, observed as the formation of
      an interfacial layer with tag-like structures. CONCLUSIONS: All the cements
      tested were bioactive. The cements release some of their components in PBS,
      triggering the initial precipitation of amorphous calcium phosphates, which act
      as precursors during the formation of carbonated apatite. This spontaneous
      precipitation promotes a biomineralization process that leads to the formation of
      an interfacial layer with tag-like structures at the cement-dentin interface.

PMID- 19410095
TI  - Radiopacity of portland cement associated with different radiopacifying agents.
AB  - This study evaluated the radiopacity of Portland cement associated with the
      following radiopacifying agents: bismuth oxide, zinc oxide, lead oxide, bismuth
      subnitrate, bismuth carbonate, barium sulfate, iodoform, calcium tungstate, and
      zirconium oxide. A ratio of 20% radiopacifier and 80% white Portland cement by
      weight was used for analysis. Pure Portland cement and dentin served as controls.
      Cement/radiopacifier and dentin disc-shaped specimens were fabricated, and
      radiopacity testing was performed according to the ISO 6876/2001 standard for
      dental root sealing materials. Using Insight occlusal films, the specimens were
      radiographed near to a graduated aluminum stepwedge varying from 2 to 16 mm in
      thickness. The radiographs were digitized and radiopacity compared with the
      aluminum stepwedge using Digora software (Orion Corporation Soredex, Helsinki,
      Finland). The radiographic density data were converted into mmAl and analyzed
      statistically by analysis of variance and Tukey-Kramer test (alpha = 0.05). The
      radiopacity of pure Portland cement was significantly lower (p < 0.05) than that
      of dentin, whereas all cement/radiopacifier mixtures were significantly more
      radiopaque than dentin and Portland cement alone (p < 0.05). Portland
      cement/bismuth oxide and Portland cement/lead oxide presented the highest
      radiopacity values and differed significantly from the other materials (p <
      0.05), whereas Portland cement/zinc oxide presented the lowest radiopacity values
      of all mixtures (p < 0.05). All tested substances presented higher radiopacity
      than that of dentin and may potentially be added to the Portland cement as
      radiopacifying agents. However, the possible interference of the radiopacifiers
      with the setting chemistry, biocompatibility, and physical properties of the
      Portland cement should be further investigated before any clinical recommendation
      can be done.

PMID- 19410096
TI  - Evaluation of ultrasonic and ErCr:YSGG laser retrograde cavity preparation.
AB  - Root end cavity preparation techniques aim to create a clean and properly shaped
      cavity in a short time. Although the use of ultrasonics has been widely
      recommended, a laser can also be used. This study evaluated the time required and
      quality of retrograde cavity preparations using ultrasonics or ErCr:YSGG laser.
      Thirty single-rooted teeth were instrumented, root filled, submitted to
      apicectomies, and grouped. Root end cavities were prepared by using the
      following: group 1 (G1): CVD (6.1107-6) ultrasonic retrotips (CVD-Vale, Sao Jose
      dos Campos, Brazil); group 2 (G2): EMS (DT-060/Berutti) ultrasonic retrotips
      (EMS, LeSentier, Switzerland); and group 3 (G3): ErCr:YSGG (G6/Waterlase; Biolase
      Technology, San Clemente, CA) laser tips. The time taken to complete the
      preparation was recorded. Epoxy resin replicas of the root apices were examined
      under a scanning electron microscope. The parameters for evaluation were the
      presence of fractures, and the quality of the preparations. The Waterlase showed
      the highest mean time for preparation of the root end cavities (p < 0.05), and
      there was no significant difference between the CVD and EMS groups (p > 0.05).
      Fractures in the cavosurface angle occurred only in G2. G1 and G2 showed better
      scores for quality of preparation than G3 (p < 0.05). These results suggest that
      root end cavities should be prepared by ultrasonic tips.

PMID- 19410097
TI  - Pulp revascularization of immature teeth with apical periodontitis: a clinical
      study.
AB  - INTRODUCTION: The purpose of this study was to examine the effect of a pulpal
      revascularization procedure for immature necrotic teeth with apical
      periodontitis. METHODS: Twelve patients, each with an immature permanent tooth
      with chronic or acute apical periodontitis, were recruited. A triantibiotic mix
      (ciprofloxacin, metronidazole, and minocycline) was used to disinfect the pulp
      for 1 week. Then a blood clot was created in the canal, over which grey mineral
      trioxide aggregate was placed. Patients were recalled periodically. RESULTS: Six
      patients dropped from the study (as a result of pain or failure to induce
      bleeding after canal disinfection) and instead received a standard apexification
      procedure. Another 3 patients did not attend any recall appointments. The
      remaining teeth (n = 3) were found to exhibit complete root development, with a
      positive response to pulp testing. CONCLUSIONS: Revascularization could be
      effective for managing immature permanent teeth with apical periodontitis with
      appropriate case selection.

PMID- 19410098
TI  - The quest for rational chronic pain pharmacotherapy.

PMID- 19410099
TI  - Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic
      reviews.
AB  - OBJECTIVES: Chronic pain is one of the most prevalent, costly and disabling
      conditions in both clinical practice and the workplace, yet often remains
      inadequately treated. Moreover, chronic pain commonly co-occurs with depression,
      anxiety and somatoform disorders, and adversely affects response of these
      conditions to psychiatric treatments. This article provides an evidence-based
      approach to the pharmacotherapy of chronic pain. METHODS: This narrative review
      is derived largely from meta-analyses and systematic reviews published since
      2005. For a few medications, findings from multiple recent trials are synthesized
      if a systematic review had not yet been published. Classes of medications are
      first reviewed, followed by an overview of four common pain disorders:
      neuropathic pain, low back pain, fibromyalgia and osteoarthritis. RESULTS: A
      stepped care approach based upon existing evidence includes (1) simple analgesics
      (acetaminophen or nonsteroidal anti-inflammatory drugs); (2) tricyclic
      antidepressants (if neuropathic, back or fibromyalgia pain) or tramadol; (3)
      gabapentin, duloxetine or pregabalin if neuropathic pain; (4) cyclobenzaprine,
      pregabalin, duloxetine, or milnacipran for fibromyalgia; (5) topical analgesics
      (capsaicin, lidocaine, salicylates) if localized neuropathic or arthritic pain;
      and (6) opioids. Disease-specific recommendations for neuropathic, low back,
      fibromyalgia and osteoarthritis pain are reviewed. CONCLUSIONS: A number of
      medications have proven effective in chronic pain disorders and their use
      individually or in combination should improve the management of chronic pain.

PMID- 19410100
TI  - Comorbid depression and increased health care utilisation in individuals with
      diabetes.
AB  - OBJECTIVE: The objective of this study was to examine the extent of health care
      utilisation (excluding costs) of diabetic patients with and without depressive
      symptoms attending a specialist clinic in Singapore. METHODS: A total of 537
      Asian outpatients (aged 21 years and above) who were attending a Diabetes Centre
      were recruited on a consecutive basis between August 2006 and February 2007.
      Sociodemographic data, clinical and health care utilisation data were collected
      from the participants. Depressive symptoms were assessed using the Center for
      Epidemiologic Studies Depression Scale. RESULTS: Individuals with depressive
      symptoms, on average, had more hospitalizations and hospitalization days. Those
      with depression reported losing significantly more working days as compared to
      the nondepressed individuals (1.9 vs. 1.4, P=.001). CONCLUSIONS: Our findings in
      this population suggest that the presence of depressive symptoms has an
      independent effect on the greater utilization of medical services.

PMID- 19410101
TI  - Symptom indicator of severity of depression in cancer patients: a comparison of
      the DSM-IV criteria with alternative diagnostic criteria.
AB  - OBJECTIVE: The objective of this study was to explore the performances of several
      diagnostic criteria items for judging the severity of major depression among
      cancer patients. METHOD: Using modern item response theory, we examined the
      performances of the diagnostic criteria outlined by the DSM-IV and two sets of
      conceptual diagnostic criteria (the Endicott and the Cavanaugh criteria) in a
      series of 728 cancer patients who had been diagnosed with major depression using
      an inclusive approach. RESULTS: While all the DSM-IV diagnostic criteria,
      including feelings of worthlessness and suicidal ideation, had a low ability for
      discriminating the severity of depression, two proposed items (not participating
      in medical care and social withdrawal) appeared to be good markers of moderately
      severe major depressive disorder among cancer patients. In addition, the items
      "fearfulness or depressed appearance in face or body posture" and "brooding, self
      pity or pessimism" may be good markers for mild major depressive disorders, while
      the item "cannot be cheered up, doesn't smile, no response to good news or funny
      situations" may be a good marker for severe major depressive disorder.
      CONCLUSIONS: The findings of the present study suggest that alternative criteria
      may have utility in diagnosing depression severity in cancer patients.

PMID- 19410102
TI  - Psychiatric morbidity in gynecological and otorhinolaryngological outpatients: a
      comparative study.
AB  - OBJECTIVE: Assessment of the point prevalence of psychiatric disorders in a
      gynecological outpatient population compared to a control group consisting of
      otorhinolaryngological outpatients. METHODS: During an 11-month period of time,
      150 unselected, consecutive gynecologic outpatients and 150 matched controls
      (otorhinolaryngological outpatients) were enrolled in the study. Patients were
      screened for psychiatric disorders using the Patient Health Questionnaire (PHQ).
      Sociodemographic data, psychiatric and medical history including inpatient
      treatments and outpatient contacts, and utilisation of the health care system
      were assessed. RESULTS: Within the gynecological group, 45.3% fulfilled the
      diagnostic criteria for at least one psychiatric diagnosis according to the PHQ,
      compared to 27.3% of the otorhinolaryngological control group (P=.002). With
      respect to distinct diagnoses, gynecological patients suffered significantly more
      often from somatoform disorders (P=.001) and depressive disorders (P=.003) than
      controls. Less than half of subjects of either group with any psychiatric
      diagnosis had ongoing psychiatric or psychotherapeutic treatment. CONCLUSIONS: We
      found a significant group difference in the number of psychiatric diagnoses
      between gynecological and otorhinolaryngological female outpatients. Psychiatric
      disorders may be frequent and unrecognised in women presenting in an outpatient
      setting, especially in those seeking medical care for gynecological problems. The
      PHQ may be a useful tool to detect psychiatric disorders even in busy clinical
      settings.

PMID- 19410104
TI  - Detecting depression during pregnancy and associated lifestyle practices and
      concerns among women in a hospital-based obstetric clinic in Jamaica.
AB  - OBJECTIVE: Antenatal depression, despite its association with increased maternal
      morbidity risks, is understudied in the developing world. We determined the rate
      and predictors of depression throughout pregnancy and the use of medication in
      women attending an obstetric clinic. METHOD: Prospective longitudinal study of
      452 women newly registered at the antenatal clinic at the University Hospital of
      the West Indies between September 2005 and February 2006. Sociodemographic data,
      clinical information and self reports of depression using Edinburgh Postnatal
      Depression Scale (EPDS) were gathered over three trimesters. RESULTS: On average,
      25% of women were identified as having a probable depressive disorder over the
      three trimesters. Independent demographic predictors were youth and unemployment
      (P<05). Planned pregnancy, exercising, not smoking, being married and support
      from physician and family were protective factors (P<.05). Using a multivariable
      model, prior history of depression was the strongest predictor of depression
      during pregnancy. Of those taking medication for depression prior to pregnancy,
      only 1.6% remained on medication during the pregnancy. CONCLUSIONS: Poverty
      related factors and lifestyle are associated with higher EPDS scores during
      pregnancy in Jamaican women. A protocol of psychosocial management in obstetric
      care is discussed along with recommendations for future research.

PMID- 19410105
TI  - High prevalence of hypokalemia in acute psychiatric inpatients.
AB  - BACKGROUND: Hypokalemia is an easily identifiable, clinically important but
      commonly neglected condition in psychiatric patients. This study intended to
      examine the prevalence of hypokalemia and its clinical correlates in acute
      psychiatric inpatients. METHOD: This retrospective study was conducted over a 6
      month period in 2008. The case notes, computerized records and laboratory results
      of all patients who were consecutively admitted to the acute psychiatric wards in
      a University-affiliated regional psychiatric unit were studied. RESULT: Three
      hundred forty-seven patients out of 440 admissions were studied. Hypokalemia, as
      defined by serum potassium level of less than 3.5 mmol/L, was found in 20.5% of
      patients with a higher prevalence in psychotic patients (27.7%). The mean
      potassium level of psychotic patients was lower than that of the overall study
      population (3.72 vs. 3.81 mmol/L, P<.05). White cell counts among the hypokalemic
      patients were higher than those without hypokalemia (7.8 vs. 7.1 x 10(9)/L,
      P=.02). CONCLUSION: Hypokalemia was common among acute psychiatric inpatients.
      Both agitation and the use of antipsychotics were postulated to contribute to the
      high prevalence of hypokalemia among acutely ill psychiatric patients.

PMID- 19410106
TI  - A comparison of anxiety, depression and quality of life between device shock and
      nonshock groups in implantable cardioverter defibrillator recipients.
AB  - BACKGROUND: Using standardized scales, we assessed the point prevalence, the
      severity of anxiety and depressive disorders, and the quality of life (QOL) in
      implantable cardioverter defibrillator (ICD) recipients who received a device
      shock. METHODS: Forty research subjects with device shocks (Group 1) and 25
      without shocks (Group 2) were interviewed after ICD implantation using the Mini
      International Neuropsychiatric Interview (MINI), the Hospital Anxiety and
      Depression Scale (HADS) and the Medical Outcomes Study 36-Item Short Form Health
      Survey (SF-36). RESULTS: The point prevalence of anxiety disorders was higher in
      Group 1 (37.5%) than in Group 2 (8%) (P=.009). Depressive symptoms scores were
      higher in Group 1 (4.75) than in Group 2 (2.24) (P=.04)), but the prevalence of
      depressive disorders or the anxiety scores were not significantly different. A
      positive correlation was found between the number of shocks and the depressive
      symptoms scores (P=.05, r=0.24); there was a negative correlation between the
      mental health subscore of the SF-36 and the number of shocks (r=-0.36, P=.003).
      The point prevalence of depressive disorders was higher in the group with
      congenital cardiac diseases (50%) than in the valvular (8%) and ischemic groups
      (23%) (P=.04), and the mental health composite summary score of the SF-36 was
      lower in this group (46.34) than in those with valvular and ischemic disease
      (56.09 and 52.61, respectively) (P=.03). CONCLUSION: Exposure to shocks may lead
      to an increased risk of anxiety and depressive symptoms. Research subjects
      receiving a high number of shocks and research subjects with congenital
      cardiovascular diseases were at higher risk of depressive symptoms or at higher
      risk of poorer psychological aspects of QOL.

PMID- 19410103
TI  - The Indiana Cancer Pain and Depression (INCPAD) trial Design of a telecare
      management intervention for cancer-related symptoms and baseline characteristics
      of study participants.
AB  - OBJECTIVE: Pain and depression are two of the most prevalent and treatable cancer
      related symptoms, each present in at least 20-30% of oncology patients. Both
      symptoms are frequently either unrecognized or undertreated, however. This
      article describes a telecare management intervention delivered by a nurse
      psychiatrist team that is designed to improve recognition and treatment of pain
      and depression. The enrolled sample is also described. METHODS: The Indiana
      Cancer Pain and Depression study is a National Cancer Institute-sponsored
      randomized clinical trial. Four hundred five patients with cancer-related pain
      and/or clinically significant depression from 16 urban or rural oncology
      practices throughout Indiana have been enrolled and randomized to either the
      intervention group or to a usual-care control group. Intervention patients
      receive centralized telecare management coupled with automated home-based symptom
      monitoring. Outcomes will be assessed at 1, 3, 6 and 12 months by research
      assistants blinded to treatment arms. RESULTS: Of 4465 patients screened, 2185
      (49%) endorsed symptoms of pain or depression. Of screen-positive patients, about
      one-third were ineligible (most commonly due to pain or depression not meeting
      severity thresholds or to pain that is not related to cancer). Of the 405
      patients enrolled, 32% have depression only, 24% have pain only and 44% have both
      depression and pain. At baseline, participants reported an average of 16.8 days
      out of the past 4 weeks during which they were confined to bed or had to reduce
      their usual activities by > or =50% due to pain or depression. Also, 176 (44%)
      reported being unable to work due to health reasons. CONCLUSIONS: When completed,
      the Indiana Cancer Pain and Depression trial will test whether centralized
      telecare management coupled with automated home-based symptom monitoring improves
      outcomes in cancer patients with depression and/or pain. Findings will be
      important for both oncologists and mental health clinicians confronted with
      oncology patients' depression or pain.

PMID- 19410107
TI  - Is intimate partner violence associated with HIV infection among women in the
      United States?
AB  - OBJECTIVE: This study sought to examine the association between intimate partner
      violence (IPV) and human immunodeficiency virus (HIV) infection among a large
      representative sample of US women. METHODS: Data came from the National
      Epidemiologic Survey on Alcohol and Related Conditions (age, 20 years and older).
      The present analysis utilized the subsample of women who reported being in a
      relationship in the last year (n=13,928). Participants were asked whether they
      had experienced physical or sexual violence from their partner in the last year,
      as well as whether they had been diagnosed with HIV by a health care
      professional. RESULTS: Past year IPV and HIV prevalence estimates among women in
      romantic relationships in the United States were 5.5% and 0.17%, respectively. In
      models adjusting for sociodemographic factors and risky sexual behaviors (e.g.,
      age of first intercourse), IPV was significantly associated with HIV infection
      (adjusted odds ratios=3.44, 95% confidence interval=1.28-9.22). We also found
      that 11.8% of the cases of HIV infection among women were attributable to past
      year IPV. CONCLUSIONS: The present study demonstrates a strong association
      between IPV and HIV in a representative sample of US women. Screening and
      prevention programs need to be aware of this important association.

PMID- 19410108
TI  - How reviews covered the unfolding scientific story of gabapentin for bipolar
      disorder.
AB  - BACKGROUND: Despite the lack of randomized controlled trials (RCTs), gabapentin
      use increased rapidly in the 1990s for mental health conditions. Subsequent RCTs
      did not demonstrate efficacy for bipolar disorder (BD). We examined the
      characteristics of review articles to determine their potential role in the
      growth of gabapentin for BD. METHODS: We searched MEDLINE, the International
      Pharmaceutical Abstracts and LexisNexis for review articles or commentaries
      examining the role of gabapentin for BD. Electronic searches were supplemented by
      manual searches of reference lists. Articles were abstracted for the types of
      evidence cited, source of evidence, the proportion of available RCTs cited and
      narrative blurbs discussing the role of gabapentin for BD. Review articles were
      classified as narrative versus systematic and positive, neutral or negative
      regarding the role of gabapentin in BD. RESULTS: We included 27 review articles
      published between 1998 and 2008, but no commentaries met eligibility criteria.
      Most did not describe potential conflicts of interest or a funding source, and
      the 3 systematic reviews were of low quality. The 11 reviews published prior to
      the first RCT of gabapentin for BD cited uncontrolled trials or case series
      (n=9), basic science (n=6), chart reviews (n=3) or unpublished RCTs (n=2). Six
      recommended gabapentin, 3 were neutral and 2 were negative. The 16 articles
      published after the first gabapentin RCT continued to cite uncontrolled trials
      and basic science; only 5 cited all the available RCTs. However, more of these
      reviews (n=10) reached negative conclusions about the role of gabapentin for BD.
      CONCLUSIONS: Narrative and low-quality systematic reviews, principally those
      published prior to RCTs, may have contributed to the growth of gabapentin use for
      BD. High-quality systematic reviews are needed to inform clinicians and
      policymakers about the effectiveness of new treatments.

PMID- 19410109
TI  - Perinatal risk factors and obsessive-compulsive spectrum disorders in patients
      with rheumatic fever.

PMID- 19410110
TI  - Loss of vision secondary to obsessive-compulsive disorder: a case report.
AB  - OBJECTIVE: To report a rare case of self-inflicted eye injury secondary to
      obsessive-compulsive disorder (OCD). METHOD: Case report. RESULTS: A 41 year-old
      patient had significant bilateral visual loss and blunt trauma through touching
      his ocular cavities due to recurrent doubts regarding their shape and urges to
      check the format of bones and cartilages. Differential diagnosis with tic
      disorders is discussed, and the patient's treatment approach is described.
      CONCLUSION: Although rare, severe clinical complications can occur in OCD.

PMID- 19410111
TI  - Self-limited erythema multiforme with risperidone.

PMID- 19410112
TI  - Toxic epidermal necrolysis associated with paroxetine.

PMID- 19410114
TI  - Depression, physical activity and glycemic control in adults with type 2
      diabetes.

PMID- 19410113
TI  - Anxiety disorders and joint hypermobility syndrome: the role of collagen tissue.

PMID- 19410115
TI  - Letter to the Editor - "longitudinal effects of depression and glycemic control
      in veterans with type 2 diabetes" by Richardson et al.

PMID- 19410116
TI  - Coexistence of acute hearing loss with retinal artery occlusion and
      encephalopathy.
AB  - We characterize 2 cases with sensorineural hearing loss and ophthalmologic
      findings. The clinicopathologic features revealed diagnosis of Susac's syndrome,
      a rare microangiopathy with cochlea, retinal, and brain affection. Diagnosis may
      be difficult because most specialists are not familiar with this angiopathy.
      However, the characteristic symptoms can mimic different pathologies, which may
      result in attention of radiologists, ophthalmologists, neurologists and
      otolaryngologists. In this report, we present 2 women with Susac's syndrome
      unveiled by audiometry, magnetic resonance imaging of the brain, and
      ophthalmologic findings. The course of the illness and a review of literature are
      presented.

PMID- 19410117
TI  - Cost-effective airway cultures in the cystic fibrosis patient.
AB  - BACKGROUND: Cystic fibrosis (CF) patients have a high incidence of multidrug
      resistant infections, rendering CF patients a treatment challenge. OBJECTIVE: To
      evaluate culture protocols for CF patients and develop a cost-effective culture
      regimen that identifies clinically relevant pathogens. STUDY DESIGN:
      Retrospective review. METHODS: At the time of endoscopic sinus surgery, CF
      patients underwent both sinus and bronchial lavage cultures. Medical records from
      2002 to 2006 were reviewed. RESULTS: Twenty-four cases were identified; 12 had
      complete sets of cultures. Seven of 12 had sinus aerobic bacteria that were also
      present in bronchial culture. Anaerobic cultures from both sites were all
      negative (42%) or nondiagnostic (58%). Thirty-three percent of sinus fungal
      cultures and 91.6% of bronchial fungal cultures were positive. Sinus acid fast
      bacillus cultures were all negative. CONCLUSION: CF culture protocols may be
      streamlined by eliminating all anaerobic cultures, as well as sinus acid fast
      bacillus and fungal cultures for a 52% reduction in cost.

PMID- 19410118
TI  - Endoscopic sialolith removal: orientation and shape as predictors of success.
AB  - PURPOSE: To identify factors that may influence successful retrieval of salivary
      stones with interventional sialendoscopy. MATERIALS AND METHODS: A retrospective
      chart review of sialendoscopy procedures performed in the Department of
      Otolaryngology at the University of Pittsburgh from July 2005 to August 2007 was
      conducted. We identified thirty consecutive cases of sialolithiasis treated with
      sialendoscopy. RESULTS: The mean age at presentation was 45 years (range, 7-77
      years) with a male-to-female sex ratio of 1:1.5. The most common presentation was
      recurrent or persistent salivary gland swelling (53%), followed by salivary gland
      swelling associated with meals (37%). All these procedures were performed under
      sedation or general anesthesia. Size of the stones ranged from 0.2 to 1.2 cm. Our
      success rate for their endoscopic removal was 74% (14/19). Four patients (4/30)
      required a planned combined technique for stone removal. CONCLUSIONS:
      Sialendoscopy is a reasonable minimally invasive option to treat sialolithiasis
      that avoids the need for salivary gland excision. Salivary stones larger than 4
      mm for submandibular cases and 3 mm for parotid cases may be amenable to
      endoscopic removal provided their largest dimension is orientated favorably along
      the length of the duct.

PMID- 19410119
TI  - Analysis of 60 patients after tympanotomy and sealing of the round window
      membrane after acute unilateral sensorineural hearing loss.
AB  - OBJECTIVE: This retrospective study was performed to evaluate the effectiveness
      of tympanotomy and sealing of the round window membrane after unilateral acute
      hearing loss. DESIGN: All patients presenting idiopathic sudden hearing loss,
      acoustic, or barotrauma were treated with prednisolone and caroverine. Thirty-six
      patients had a mean pure tone hearing level worse than 70 dB. Recovery was
      defined as improvement of hearing threshold for 5 frequencies (250, 500, 1000,
      2000, and 4000 Hz). If hearing did not improve after conservative treatment, an
      exploratory tympanotomy and sealing of the round window membrane were suggested.
      In the last 8 years, 60 patients with idiopathic sudden hearing loss, acoustic,
      or barotrauma underwent tympanotomy. RESULTS: In 40 patients, we observed
      improvement of hearing level up to complete remission. In 20 patients, no change
      could be detected. In the group of patients with documented barotrauma, 12
      patients showed improved hearing levels. Of 37 patients with idiopathic sudden
      hearing loss, 26 had an improved hearing after surgery. Most patients were
      operated on within 14 days (range, 1-60 days), but time of surgery had no
      influence on outcome in patients with idiopathic hearing loss. In contrast, in
      patients with barotrauma, time of surgery seems to have an influence on outcome.
      CONCLUSIONS: Tympanotomy and sealing of the round window membrane can be
      recommended in cases of acute hearing loss after failure of conservative
      treatment.

PMID- 19410120
TI  - Otolaryngologic manifestations of mitochondrial cytopathies.
AB  - INTRODUCTION: Primary mitochondrial cytopathies include more than 40 different
      identified diseases that have varied genetic features. The common factor among
      these diseases is that the mitochondria are unable to effectively complete
      oxidative phosphorylation to generate energy. One in 5000 children per year in
      the United Sates are born with mitochondrial disease. The term primary
      mitochondrial disease refers specifically to mitochondrial dysfunction caused by
      genetic mutations directly impacting the composition and function of the
      respiratory chain. These defects impair mitochondrial oxidative phosphorylation,
      the process by which oxidation of the end products of metabolism in the electron
      transport chain is coupled to phosphorylation of adenosine diphosphate to produce
      energy in the form of adenosine triphosphate. The effects of mitochondrial
      disease can be quite varied, and the severity of the defect may be great or
      small. We sought to find the common otolaryngologic manifestations of this
      disease, to enable better treatment of the patients. We report on 41 pediatric
      cases of mitochondrial cytopathy diagnosed from 2001 to 2006 at our Center for
      Child Neurology (Cleveland, OH). We performed a retrospective review after
      obtaining institutional review board approval. Patients who had otologic
      manifestations including recurrent otitis media and hearing loss comprise 14.6%.
      Patients who were noted to have obstructive sleep apnea requiring
      adenotonsillectomy comprise 9.8%. Patients who had dysphagia comprise 22%;
      however, all of these patients were noted to have some developmental delay and
      seizures. It was also noted that there was a 17% incidence of gastroesophageal
      reflux, and 36.6% incidence of seizures in our patient population. In conclusion,
      mitochondrial cytopathies exhibit extreme clinical variability. This variability
      greatly increases the burden for affected families and impairs our ability to
      understand the pathogenesis of these disorders. In otolaryngologic examination,
      children appear to have recurrent otitis, dysphagia, and sleep apnea, at a much
      higher incidence than the general pediatric population. A comprehensive
      management approach to these patients including pediatric neurology, genetics,
      speech pathology, otolaryngology, and audiology is essential to their care.

PMID- 19410122
TI  - Incudostapedial joint arthroplasty using temporalis fascia/perichondrium ties.
AB  - Incudostapedial joint dislocation is the most frequently found ossicular chain
      defect. In these cases reconstitution of joint capsule is important in
      maintaining joint integrity. But reconstruction of dislocated incudostapedial
      joint is a challenging procedure as this joint is devoid of any muscular or soft
      tissue support. Here we describe a technique designed to reposition the
      incudostapedial joint in its anatomical position using temporalis fascia or
      perichondrium. Data have been collected and analyzed from 42 patients with
      incudostapedial joint discontinuity. The fascial ties used for reconstruction of
      joint capsule ensure a dynamic union of the repositioned incus with stapes,
      leading to a significant improvement in conductive hearing loss.

PMID- 19410121
TI  - Sensorineural hearing loss in patients with inflammatory bowel disease.
AB  - OBJECTIVE: The study aimed to discuss the association between sensorineural
      hearing loss (SNHL) and inflammatory bowel disease (IBD). METHODS: We reviewed
      cases of patients with known IBD seen in an otolaryngology practice with
      documentation of all otologic data including age of onset, family history of
      otologic problems, exposure to noise, audiometric findings, and so on. RESULTS:
      Of 38 patients with a history of IBD, 22 had documented SNHL. Nineteen of these
      had no other identifiable etiology for their inner ear dysfunction. Fourteen of
      these patients had a diagnosis of ulcerative colitis and 5 had Crohn disease.
      Sixteen patients had bilateral SNHL, and 3 patients had unilateral SNHL. Only one
      patient had a lasting response of SNHL to medical treatment. CONCLUSION: This
      review suggests that SNHL is an extraintestinal association of IBD. As IBD is
      considered to be a local or systemic immunopathy, the associated SNHL might also
      be an expression of systemic immune dysfunction.

PMID- 19410123
TI  - Quality of life in head and neck cancer survivors: a cross-sectional survey.
AB  - PURPOSE: Head and neck cancer (HNC) survivors have substantial psychological
      distress in addition to treatment-related side effects. This study examines the
      long-term quality of life (QOL) of HNC survivors in a busy tertiary care center.
      MATERIAL AND METHODS: A prospective, cross-sectional survey was conducted
      studying 212 HNC survivors 1 year after completion of their treatment at a
      tertiary cancer center. Quality of life assessments were performed using the 2
      standardized health-related QOL questionnaires: The European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and The
      Quality of Life Questionnaire Head and Neck Cancer Module. RESULTS: The overall
      global QOL rating for the study cohort was satisfactory. The European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      Core-30 scores showed that the domains where most patients faired poorly included
      financial difficulties (54%), appetite loss (36%), fatigue (33%), and cough
      (30%). The Quality of Life Questionnaire Head and Neck Cancer Module scale
      identified the domains with poor scores to be dry mouth (64%), dental problems
      (42%), sticky saliva (40%), cough (39%), and problems with mouth opening (32%).
      Patients with early-stage tumors and those treated with surgery alone had
      significantly better QOL scores when compared with advanced stage tumors and
      patients receiving either radiation alone or multimodality treatment,
      respectively. CONCLUSIONS: Quality of life questionnaires provide a medium for
      patients to effectively communicate with their physician in a busy tertiary care
      facility and provide an insight into the physical, psychological, and social
      problems affecting our patients which can then direct future interventions.

PMID- 19410124
TI  - Nonmelanoma skin cancer of the head and neck II: surgical treatment and
      reconstruction.
AB  - Surgical treatment of non-melanoma skin cancers (NMSC) is most often straight
      forward and can be performed as an office-based procedure by non-surgically
      trained professionals. However, the cases that present to an Otolaryngology
      practice typically will involve difficult-to-treat lesions around the face and
      lesions that necessitate an in depth knowledge of how to balance the need for
      adequate surgical margins with the reconstructive contraints imposed by aesthetic
      subunits of the face. This article discusses modern concepts of surgical margins
      for NMSC, including the Moh's micrographic surgical technique, and then reviews
      the most common reconstructive strategies for difficult-to-treat areas on the
      face. The goal of this paper is to help the general Otolaryngollogists to
      understand the basic principles of surgical resection and reconstruction of NMSC
      lesions on the face.

PMID- 19410125
TI  - Communication routes between intracranial spaces and inner ear: function,
      pathophysiologic importance and relations with inner ear diseases.
AB  - OBJECTIVE: There exist 3 communication routes between the intracranial space and
      the inner ear, the vestibular aqueduct, the cochlear aqueduct, and the internal
      auditory canal. They possess a key role in inner ear pressure regulation and
      fluid homeostasis and are related to inner ear diseases. REVIEW METHODS: Relevant
      literature was reviewed, and the current knowledge of the anatomy, physiologic
      importance, and relations to inner ear diseases were described. Pathologic
      communication routes such as semicircular canal dehiscence syndrome were
      highlighted as well. CONCLUSION: Abnormalities in all 3 communication routes may
      predispose or be the cause of distinct inner ear pathologic condition and
      involved in other cochlear and vestibular syndromes, in which their role is not
      completely clear. The increasing knowledge of the underlying mechanisms
      encourages promising approaches for possible intervention in the future.

PMID- 19410126
TI  - Protrusion of a migrated fish bone in the neck.
AB  - Uningested fish bone swallowing is common, but protrusion of the unswallowed fish
      bone from the neck is very rare. We report a 3-cm fish bone, which was not
      diagnosed during the patient first visit at emergency room, resulting in a
      protrusion out of the patient's neck skin 21 days later after ingurgitation of
      the bone. The migrated fish bone was safety pulled out directly after obtaining
      computed tomography of the neck to make sure no soft tissue or major artery
      involved. Migration of ingested fish bone is an uncommon complication, which has
      the potential risk to cause morbidity and mortality. Therefore, if findings of
      physical examination, x-rays, or laryngoscope are negative, it is important to
      recheck the patient if sore throat persists. Obtaining a neck computed tomography
      or performing gastroendoscopy to rule out the possible mis-swallowing of fish
      bone should be warranted. To the authors' knowledge, such a case has not been
      previously reported in medical literature.

PMID- 19410127
TI  - Cardiac metastasis after squamous cell carcinoma of the base of tongue.
AB  - OBJECTIVES: Metastases to the heart are rare. We report a case of squamous cell
      carcinoma of the base of tongue secondarily complicated with cardiac metastasis 6
      months after surgical treatment resulted in successful local control. METHODS:
      The lesion was found using computerized axial tomography in a patient with
      minimal cardiologic symptoms. RESULTS: The patient died shortly due to
      complications of his metastatic disease. No curative treatment was possible.
      CONCLUSIONS: Cardiac metastasis should be suspected when new cardiovascular
      symptoms are observed in patients with a history of head and neck neoplasm. The
      prognosis of the condition typically is inevitably fatal.

PMID- 19410128
TI  - Sjogren's syndrome masquerading as nasopharyngeal carcinoma.
AB  - OBJECTIVE: The aim of the study was to describe a case of nasopharyngeal
      involvement by Sjogren's syndrome masquerading as nasopharyngeal carcinoma.
      METHODS: A description of clinical and radiologic features of facial pain,
      nasopharyngeal bulge, middle ear effusion, restriction of palatal movement, and
      infiltrating nasopharyngeal mass on imaging was given. Histologic evaluation,
      response to treatment with steroids and hydrochloroquine, and long-term follow
      up, however, subsequently indicated the mass to be secondary to Sjogren's
      syndrome. CONCLUSION: A previously undescribed manifestation of Sjogren's
      syndrome is described.

PMID- 19410129
TI  - Wegener's granulomatosis of the pediatric airway: a case demonstrating a
      conservative management approach.
AB  - OBJECTIVE: Subglottic stenosis is found in 10% to 20% of patients with Wegener's
      granulomatosis, and at times, it may be the only indication of disease. This is
      particularly a problem in childhood-onset Wegener's granulomatosis, which is
      complicated 5 times more by subglottic and tracheal stenosis than in adult-onset
      disease. Because this is a rare disease that is often misdiagnosed as reactive
      airway disease in childhood, the discovery of subglottic stenosis is delayed
      until much of the chronic damage has already been done. This report discusses the
      diagnosis and management of a 12-year-old male with a severe, actively inflamed
      subglottis and trachea because of Wegener's granulomatosis. METHOD: This study
      uses a retrospective case review. RESULTS: The study shows a successful
      symptomatic medical treatment of subglottic stenosis with resolution of tracheal
      inflammation and subglottic stenosis. CONCLUSION: Treatment of an actively
      inflamed trachea with subglottic stenosis because of Wegener's granulomatosis
      should focus on medical therapy, including steroids, before making attempts at
      surgical intervention.

PMID- 19410130
TI  - Metastatic calcification involving the true vocal cord.
AB  - Metastatic calcification (MC) commonly results secondary to phosphorus and
      calcium dysregulation in end-stage renal disease (ESRD). Only once before has MC
      been reported to involve a true vocal cord. A 35-year-old man with ESRD and
      secondary hyperparathyroidism was evaluated for hoarseness. Three years ago, he
      underwent a total parathyroidectomy with parathyroid autograft to the forearm.
      Simultaneously, he had a left lobe thyroidectomy that displayed a papillary
      thyroid carcinoma. Since that time, he continued to have hyperphosphatemia and
      hypocalcemia. Laryngoscopy displayed a small papillomatous lesion on the right
      true vocal cord. He underwent excision of the vocal cord lesion; histologic
      examination demonstrated benign squamous epithelium with extensive submucosal
      calcification. In patients with ESRD with secondary dysregulation of serum
      phosphorus to calcium level balance, MC may involve variable anatomical
      locations, including the true vocal cords. Regarding histologic findings,
      pathologists must consider malignancies associated with calcification, mimicking
      a benign process.

PMID- 19410131
TI  - Giant laryngeal angioleiomyomas: a case report with review of literature.
AB  - We report a recently encountered case of vascular leiomyoma in the larynx, a
      benign tumor that is rare in the organ, in a 52-year-old man. Chief complaints
      were a progressive hoarseness, laryngeal pain, deglutitive uncomfortableness and
      dyspnea in the supine position. Laryngoscope revealed many spherical tumors
      interlacing together with a smooth surface, measuring approximately 2x4 cm and
      covered with normal mucosa, found at the side of laryngeal epiglottis from its
      margin to supraglottis. Tracheotomy was performed under local anesthesia, and
      laryngosurgery was then carried out under general anesthesia. Histologic study
      showed smooth muscle cell proliferation, especially surrounded by an abundance of
      blood vessels, and the tumor was diagnosed as a vascular leiomyoma. Its complete
      resection was the best therapeutic option. Tracheotomy was required in this case
      depending on the occurrence site if the tumor and its size.

PMID- 19410133
TI  - The Neuroscience Peer Review Consortium.

PMID- 19410132
TI  - Real-time myocardial contrast echocardiography in rat: infusion versus bolus
      administration.
AB  - To compare the feasibility of real-time myocardial contrast echocardiography
      (MCE) in rats with infusion and bolus administration of a second-generation
      ultrasound contrast agent BR1. B-mode real-time MCE was performed in 12 Sprague
      Dawley rats following the BR1 infusion or bolus injection. The myocardium signal
      intensity (SI) was plotted against time and was fitted to exponential functions.
      The plateau SI (A) and rate of SI increase (beta) for the infusion study and peak
      signal intensity (PSI) for the bolus study were obtained. (99m)Tc-Sestamibi and
      Evans blue were used to assess myocardial blood perfusion and to calculate the
      myocardium perfusion defect area ex vivo. High-quality real-time MCE images were
      successfully obtained using each method. At baseline, all LV segments showed even
      contrast distribution. Following left anterior descending coronary artery (LAD)
      ligation, significant perfusion defect was observed in LAD beds with a
      significantly decreased A* beta and PSI values compared with LCx beds (Infusion:
      A*beta (LAD): 5.42 +/- 1.57 dB, A*beta (LCx): 46.52 +/- 5.32 dB, p < 0.05; Bolus:
      PSI (LAD): 2.11 +/- 0.67 dB, PSI (LCx): 20.68 +/- 0.72 dB, p < 0.05), which was
      consistent with (99m)Tc-Sestamibi distribution findings. Myocardial perfusion
      defect areas, assessed by both methods, showed no differences and showed good
      correlation with Evans blue staining. ED frames were more favorable for imaging
      analysis. Both infusion and bolus administration of the contrast agent combined
      with real-time MCE technique can provide a reliable and noninvasive approach for
      myocardial perfusion assessment in rats and the infusion method was more suitable
      for quantitative analysis of myocardial blood flow.

PMID- 19410136
TI  - Revisiting the past for a look toward future research: A final editorial.

PMID- 19410138
TI  - Review of the poster "Dosimetric comparison of gamma knife radiosurgery vs. 125I
      plaque brachytherapy in a cohort of choroidal melanomas".
AB  - Historically, treatment for choroidal melanomas was surgical enucleation.
      Currently, treatment methods such as stereotactic radiosurgery and brachytherapy
      are being used to spare the eye. The poster "Dosimetric Comparison of Gamma Knife
      Radiosurgery vs. I-125 Plaque Brachytherapy in a Cohort of Choroidal Melanomas"
      presented at ASTRO 2007 by Anderson et al. provides a comparison of these
      methods. The dose to disk, fovea and lens in 29 patients from a simulated I-125
      treatment and a delivered Gamma Knife radiosurgery was compared. Thirty Gy was
      prescribed to the 50% Isodose line in the radiosurgery and 85 Gy was prescribed
      to the apex of the tumor in the I-125 simulation. It was found that the Gamma
      Knife spares the disk better in 59% of the tumors, including those >or=6.5 mm in
      height; spares the fovea better in 69% of the tumors, including those >or=5.5 mm;
      and spares lens better in only 30% of the tumors, with no distinction in size.
      Tumor location was not taken into account for this study, which could explain the
      variations in smaller tumors. For larger tumors, gamma knife will protect most
      organs at risk more effectively. This study shows how a tumor's parameters can be
      used in selecting treatment modality.

PMID- 19410137
TI  - Accuracy and precision of an IGRT solution.
AB  - Image-guided radiotherapy (IGRT) can potentially improve the accuracy of delivery
      of radiotherapy treatments by providing high-quality images of patient anatomy in
      the treatment position that can be incorporated into the treatment setup. The
      achievable accuracy and precision of delivery of highly complex head-and-neck
      intensity modulated radiotherapy (IMRT) plans with an IGRT technique using an
      Elekta Synergy linear accelerator and the Pinnacle Treatment Planning System
      (TPS) was investigated. Four head-and-neck IMRT plans were delivered to a semi
      anthropomorphic head-and-neck phantom and the dose distribution was measured
      simultaneously by up to 20 microMOSFET (metal oxide semiconductor field-effect
      transmitter) detectors. A volumetric kilovoltage (kV) x-ray image was then
      acquired in the treatment position, fused with the phantom scan within the TPS
      using Syntegra software, and used to recalculate the dose with the precise
      delivery isocenter at the actual position of each detector within the phantom.
      Three repeat measurements were made over a period of 2 months to reduce the
      effect of random errors in measurement or delivery. To ensure that the noise
      remained below 1.5% (1 SD), minimum doses of 85 cGy were delivered to each
      detector. The average measured dose was systematically 1.4% lower than predicted
      and was consistent between repeats. Over the 4 delivered plans, 10/76
      measurements showed a systematic error > 3% (3/76 > 5%), for which several
      potential sources of error were investigated. The error was ultimately
      attributable to measurements made in beam penumbrae, where submillimeter
      positional errors result in large discrepancies in dose. The implementation of an
      image-guided technique improves the accuracy of dose verification, particularly
      within high-dose gradients. The achievable accuracy of complex IMRT dose delivery
      incorporating image-guidance is within +/- 3% in dose over the range of sample
      points. For some points in high-dose gradients, submillimeter errors in position
      can lead to errors > 3%. The precision of the delivery system was demonstrated to
      be within the experimental noise of the detector system of 1.5% (1 SD).

PMID- 19410139
TI  - Effect of MLC leaf width and PTV margin on the treatment planning of intensity
      modulated stereotactic radiosurgery (IMSRS) or radiotherapy (IMSRT).
AB  - We studied the effect of MLC (multileaf collimator) leaf width and PTV (planning
      target volume) margin on treatment planning of intensity modulated stereotactic
      radiosurgery (IMSRS) or radiotherapy (IMSRT). Twelve patients previously treated
      with IMSRS/IMSRT were retrospectively planned with 5- and 3-mm MLC leaf widths
      and 3- and 2-mm PTV margins using the already contoured clinical target volume
      and critical structures. The same beam arrangement, planning parameters, and
      optimization method were used in each of the 4 plans for a given patient. Each
      plan was normalized so that the prescription dose covered at least 99% of the
      PTV. Plan indices--D(mean) (mean dose), conformity index (CI), V(70) (volume
      receiving >or= 70% of the prescription dose), and V(50) (volume receiving >or=
      50% of the prescription dose)--were calculated from the dose-volume histograms
      (DVHs) of the PTV, normal tissue, and organs at risk (OARs). Hypothesis testing
      was performed on the mean ratios of plan indices to determine the statistical
      significance of the relative differences. The PTV was well covered for all plans,
      as no significant differences were observed for D(95), V(95), D(max), D(min), and
      D(mean) of the PTV. The irradiated volume was approximately 23% smaller when 2-mm
      instead of 3-mm PTV margin was used, but it was only reduced by approximately 6%
      when the MLC leaf width was reduced from 5 mm to 3 mm. For normal tissue and
      brainstem, V(70), V(50), and D(mean) were reduced more effectively by a decrease
      in MLC width, while D(mean) of optic nerve and chiasm were more sensitive to a
      change in PTV margin. The DVH statistics for the PTV and normal structures from
      the treatment plan with 5-mm MLC and 2-mm PTV margin were equal to those with 3
      mm MLC and 3-mm PTV margin. PTV margin reduction is more effective in sparing the
      normal tissue and OARs than a reduction in MLC leaf width. For IMSRS, where
      highly accurate setup and small PTV margins are routinely employed, the use of 5
      mm MLC is therefore less desirable.

PMID- 19410140
TI  - Respiratory motional effect on cone-beam CT in lung radiation surgery.
AB  - The cone-beam CT (CBCT), which is acquired using an on-board imager (OBI)
      attached to a linear accelerator, is used effectively in the verification of
      setup accuracy for lung radiation surgery. In this study, the respiratory organ
      motional effect on the CBCT was evaluated with a properly devised phantom system,
      and the level of possible error in conditions of a real clinical process was
      assessed. In a comparison study between the CBCT in static status and CBCT images
      acquired in 20 different motional cases, we confirmed that the image quality and
      information of CBCT were degraded, with an increase of motional ranges in the
      region of inhomogeneous structures. The 4D-CT MIP (50 approximately 55%) for the
      planning of lung radiation surgery and the 4D-CT MIP (full phase) were compared
      with CBCT in the various motional cases for the evaluation of the influence of
      the motional effect on CBCT in the process of the setup error correction. The
      average ratio of relative difference between plan CT: 4D-CT MIP (50%
      approximately 55%) and CBCT was 5.79% and between plan CT: 4D-CT MIP (50%
      approximately 55%) and 4D-CT MIP (full phase) was 42.95% in the phantom study. In
      the analysis of clinical cases of lung radiation surgery, the gross tumor volumes
      were compared in each CT image. The average ratio of relative difference between
      plan CT: 4D-CT MIP (50 approximately 55%) and CBCT was 10.72% and between plan
      CT: 4D-CT MIP (50 approximately 55%) and 4D-CT MIP (full phase) was 28.19%. These
      results showed that, although a respiratory organ motional effect on CBCT
      introduced variation in image quality, the error as a result of this variation
      could be estimated relatively low in the setup error correction for a gated-lung
      radiation surgery when the planning was performed in 4D-CT MIP (50 approximately
      55%), which already included a related signal of motional effect.

PMID- 19410141
TI  - Calculation and prediction of the effect of respiratory motion on whole breast
      radiation therapy dose distributions.
AB  - The standard treatment technique used for whole-breast irradiation can result in
      undesirable dose distributions in the treatment site, leading to skin
      reaction/fibrosis and pulmonary and cardiac toxicities. Hence, the technique has
      evolved from conventional wedged technique (CWT) to segment intensity-modulated
      radiation therapy (SIMRT) and beamlet IMRT (IMRT). However, these newer
      techniques feature more highly modulated dose distributions that may be affected
      by respiration. The purpose of this work was to conduct a simple study of the
      clinical impact of respiratory motion on breast radiotherapy dose distributions
      for the three treatment planning techniques. The ultimate goal was to determine
      which patients would benefit most from the use of motion management. Eight
      patients with early-stage breast cancer underwent a free-breathing (FB) computed
      tomography (CT) simulation, with medial and lateral markers placed on the skin.
      Two additional CT scans were obtained at the end of inspiration (EI) and the end
      of expiration (EE). The FB-CT scan was used to develop treatment plans using each
      technique. Each plan was then applied to EI and EE-CT scans. Compared with the FB
      CT scan, the medial markers moved up to 1.8 cm in the anterior-superior direction
      at the end of inspiration (EI-scan), and on average 8 mm. The CWT and SIMRT
      techniques were not "sensitive" to respiratory motion, because the % clinical
      target volume (CTV) receiving 95% of the prescription dose (V(95%)) remained
      constant for both techniques. For patients that had large respiratory motion
      indicated by marker movement >0.6 cm, differences in coverage of the CTV at the
      V100% between FB and EI for beamlet IMRT plans were on the order of >10% and up
      to 18%. A linear model was developed to relate the dosimetric coverage difference
      introduced by respiration with the motion information. With this model, the
      dosimetric coverage difference introduced by respiratory motion could be
      evaluated during patient CT simulation. An appropriate treatment method can be
      chosen after the simulation.

PMID- 19410142
TI  - Intra and interfraction mediastinal nodal region motion: implications for
      internal target volume expansions.
AB  - The purpose of this study was to determine the intra and interfraction motion of
      mediastinal lymph node regions. Ten patients with nonsmall-cell lung cancer
      underwent controlled inhale and exhale computed tomography (CT) scans during two
      sessions (40 total datasets) and mediastinal nodal stations 1-8 were outlined.
      Corresponding CT scans from different sessions were registered to remove setup
      error and, in this reference frame, the centroid of each nodal station was
      compared for right-left (RL), anterior-posterior (AP), and superior-inferior (SI)
      displacement. In addition, an anisotropic volume expansion encompassing the
      change of the nodal region margins in all directions was used. Intrafraction
      displacement was determined by comparing same session inhale-exhale scans.
      Interfraction reproducibility of nodal regions was determined by comparing the
      same respiratory phase scans between two sessions. Intrafraction displacement of
      centroid varied between nodal stations. All nodal regions moved posteriorly and
      superiorly with exhalation, and inferior nodal stations showed the most motion.
      Based on anisotropic expansion, nodal regions expanded mostly in the RL direction
      from inhale to exhale. The interpatient variations in intrafraction displacement
      were large compared with the displacements themselves. Moreover, there was
      substantial interfractional displacement ( approximately 5 mm). Mediastinal lymph
      node regions clearly move during breathing. In addition, deformation of nodal
      regions between inhale and exhale occurs. The degree of motion and deformation
      varies by station and by individual. This study indicates the potential advantage
      of characterizing individualized nodal region motion to safely maximize
      conformality of mediastinal nodal targets.

PMID- 19410143
TI  - Do all patients of breast carcinoma need 3-dimensional CT-based planning? A
      dosimetric study comparing different breast sizes.
AB  - Evaluation of dose distribution in a single plane (i.e., 2-dimensional [2D]
      planning) is simple and less resource-intensive than CT-based 3-dimensional
      radiotherapy (3DCRT) planning or intensity modulated radiotherapy (IMRT). The aim
      of the study was to determine if 2D planning could be an appropriate treatment in
      a subgroup of breast cancer patients based on their breast size. Twenty
      consecutive patients who underwent breast conservation were planned for
      radiotherapy. The patients were grouped in 3 different categories based on their
      respective chest wall separation (CWS) and the thickness of breast, as "small,"
      "medium," and "large." Two more contours were taken at locations 5 cm superior
      and 5 cm inferior to the isocenter plane. Maximum dose recorded at specified
      points was compared in superior/inferior slices as compared to the central slice.
      The mean difference for small breast size was 1.93 (standard deviation [SD] =
      1.08). For medium breas size, the mean difference was 2.98 (SD = 2.40). For the
      large breasts, the mean difference was 4.28 (SD = 2.69). Based on our dosimetric
      study, breast planning only on the single isocentric contour is an appropriate
      technique for patients with small breasts. However, for large- and medium-size
      breasts, CT-based planning and 3D planning have a definite role. These results
      can be especially useful for rationalizing treatment in busy oncology centers.

PMID- 19410144
TI  - A method to automate the segmentation of the GTV and ITV for lung tumors.
AB  - Four-dimensional computed tomography (4D-CT) is a useful tool in the treatment of
      tumors that undergo significant motion. To fully utilize 4D-CT motion information
      in the treatment of mobile tumors such as lung cancer, autosegmentation methods
      will need to be developed. Using autosegmentation tools in the Pinnacle(3) v8.1t
      treatment planning system, 6 anonymized 4D-CT data sets were contoured. Two test
      indices were developed that can be used to evaluate which autosegmentation tools
      to apply to a given gross tumor volume (GTV) region of interest (ROI). The 4D-CT
      data sets had various phase binning error levels ranging from 3% to 29%. The
      appropriate autosegmentation method (rigid translational image registration and
      deformable surface mesh) was determined to properly delineate the GTV in all of
      the 4D-CT phases for the 4D-CT data sets with binning errors of up to 15%. The
      ITV was defined by 2 methods: a mask of the GTV in all 4D-CT phases and the
      maximum intensity projection. The differences in centroid position and volume
      were compared with manual segmentation studies in literature. The indices
      developed in this study, along with the autosegmentation tools in the treatment
      planning system, were able to automatically segment the GTV in the four 4D-CTs
      with phase binning errors of up to 15%.

PMID- 19410145
TI  - Characterization of the transmission of the Elekta Stereotactic Body Frame (ESBF)
      and accounting for it during treatment planning.
AB  - The purpose of this study was to measure the transmission of the Elekta
      Stereotactic Body Frame (ESBF) and treatment table, to calculate the transmission
      of the frame in the Eclipse Treatment Planning System (TPS) using analytical
      anisotropic algorithm (AAA), and to demonstrate a simple method of accounting for
      this transmission in treatment planning. A solid water body phantom was imaged
      inside the ESBF and planned with multiple 3D-CRT fields using AAA using both 6-MV
      and 16-MV energies. In the first set of plans, the frame and table were included
      in the "Body" contour and, therefore, used in the dose calculations. In the
      second set of plans, the frame and the table were not included in the "Body"
      contour and, therefore, were not incorporated in the calculations. The latter
      simulated a setup in which there was no frame or table. Eclipse TPS will only
      incorporate data from the CT set in calculations, if it is included in the "Body"
      contour. The plans were treated under two conditions: one with the phantom in the
      ESBF and one without the frame on a specially designed table. This table allows
      all the beams to enter the phantom without passing through any attenuating
      material (i.e., table or frame). Transmission of the frame and table was
      determined by the ratio of the measurements with the frame and table to the
      measurements without them. To validate the accuracy of the calculation model,
      plans with homogeneous phantom and a heterogeneous plan were compared with the
      measurements. The transmission of the frame varies from 89-94% depending on the
      angle of the beams and whether they also intercept the table. The AAA algorithm
      calculated the transmission of the frame and table to within 2% of the
      measurements for all gantry angles. Validation results showed that AAA can
      calculate the dose to the target to within 2% of the measured value. The
      attenuation caused by the ESBF must be accounted for in the planning process. For
      Eclipse, the frame should be contoured and included in all calculations. This can
      be done easily and accurately.

PMID- 19410146
TI  - Investigation of simple IMRT delivery techniques for non-small cell lung cancer
      patients with respiratory motion using 4DCT.
AB  - Techniques for generating simplified IMRT treatment plans for treating non-small
      cell lung cancer (NSCLC) patients with respiratory motion were investigated. To
      estimate and account for respiratory motion, 4-dimensional computed tomography
      (4DCT) datasets from 5 patients were used to design 5-field 6-MV ungated step-and
      shoot intensity modulated radiotherapy (IMRT) plans delivering a dose of 66 Gy to
      the planning target volume (PTV). For each patient, 2 plans were generated using
      the mean intensity and the maximum intensity of 10 CT datasets from different
      breathing phases. The plans also utilized different margins around the clinical
      target volume/internal target volume (CTV/ITV) to account for tumor motion. To
      reduce the treatment time and ensure accurate dose delivery to moving targets,
      the number of intensity levels was minimized while maintaining dose coverage to
      PTV and minimizing dose to organs at risk (OARs). Dose-volume histograms (DVHs),
      dosimetric metrics, and outcome probabilities were evaluated for all plans. Plans
      using the averaged CT image dataset were inferior, requiring larger margins
      around the PTV, with a maximum of 1.5 cm, to ensure coverage of the tumor, and
      therefore increased the dose to OARs located in proximity of the tumor. The plans
      based on superimposed CT image datasets achieved full coverage of the tumor,
      while allowing tight margins around the PTV and minimizing the dose to OARs. A
      small number of intensity-levels (3 to 5), resulting in IMRT plans with a total
      of 13 to 30 segments, were sufficient for homogeneous PTV coverage, without
      affecting the sparing of OARs. In conclusion, a technique involving treatment
      planning with the superimposed CT scans of all respiratory phases, and the
      application of IMRT with only a small number of segments was feasible despite
      significant tumor motion; however, greater patient numbers are needed to support
      the statistical significance of the results presented in this work.

PMID- 19410147
TI  - An interlaced IMRT technique for elongated tumor volumes.
AB  - Treatment of large target volumes with intensity modulated radiotherapy (IMRT)
      can be restricted by the maximum field size of the multileaf collimator (MLC). In
      this work, a straightforward technique for MLC-based IMRT is presented, which is
      generally applicable and does not depend on the capabilities of the linear
      accelerator's IMRT delivery system. A dual isocenter technique was developed that
      maximizes beam overlap. The beams at the first isocenter are arranged such that
      they interlace with the beams at the second isocenter. All beams contribute to
      the overlap region, whereas only some contribute to the superior and some to the
      inferior part of the target. The interlaced technique (9 beams) was compared with
      an alternative more complex approach (14 beams) for a head-and-neck case with
      simultaneous integrated boost and 3 different dose levels. The plans were
      compared in terms of complexity, dosimetry, and the effect of inaccurate
      translation between the isocenters. The interlaced and the more complex IMRT
      technique resulted in nearly identical dose distributions without clinically
      relevant differences. The total number of monitor units (MUs) was comparable with
      more MUs per segment for the interlaced technique. For the interlaced technique,
      the number of segments <or=5 MU was reduced by 43%. Simulation of isocenter setup
      errors of +/-1, +/-2, and +/-3 mm revealed maximum dose point errors of 1.8%,
      3.8%, and 5.4% in the target volume for the interlaced technique. The interlaced
      IMRT technique resulted in an equivalent plan to the more complex technique
      without compromising the dose distribution. The technique is less complex and is
      robust against inaccurate isocenter translations of up to +/-1 mm. Due to the
      versatility of the technique, it can easily be applied to other anatomical
      regions and is well suited for clinical routine usage.

PMID- 19410148
TI  - Consensus statement on concussion in sport--the 3rd International Conference on
      concussion in sport, held in Zurich, November 2008.

PMID- 19410149
TI  - What happens when pediatric neurosurgery patients grow up? Introduction.

PMID- 19410150
TI  - The pediatric neurosurgical patient: the challenge of growing up.
AB  - Adults treated in infancy for conditions such as spina bifida and hydrocephalus
      are not cured of their conditions even after reaching adulthood. However,
      patients who have received coordinated care within a children's facility are
      unlikely to find the same type of coordinated care when they become adults. This
      article explores the various causes of these difficulties, which are not uniform
      across geographic areas, and the need for and challenges of planning the
      transition of care of pediatric neurosurgical patients from pediatric
      neurosurgeons to general or adult neurosurgical practices.

PMID- 19410151
TI  - A contemporary definition and classification of hydrocephalus.
AB  - This review focuses on the problems related to defining hydrocephalus and on the
      development of a consensus on the classification of this common problem. Such a
      consensus is needed so that diverse research efforts and plans of treatment can
      be understood in the same context. The literature was searched to determine the
      definition of hydrocephalus and to identify previously proposed classification
      schemes. The historic perspective, purpose, and result of these classifications
      are reviewed and analyzed. The concept of the hydrodynamics of cerebrospinal
      fluid (CSF) as a hydraulic circuit is presented to serve as a template for a
      contemporary classification scheme. Finally, a definition and classification that
      include all clinical causes and forms of hydrocephalus are suggested. The
      currently accepted classification of hydrocephalus into "communicating" and
      "noncommunicating" varieties is almost 90 years old and has not been modified
      despite major advances in neuroimaging, neurosciences, and treatment outcomes.
      Despite a thorough search of the literature using computerized search engines and
      bibliographies from review articles and book chapters, I identified only 6
      previous attempts to define and classify different forms of hydrocephalus. This
      review proposes the following definition for hydrocephalus: hydrocephalus is an
      active distension of the ventricular system of the brain related to inadequate
      passage of CSF from its point of production within the ventricular system to its
      point of absorption into the systemic circulation. Based on this definition
      (potential points of flow restriction) and on the view of the CSF system as a
      hydraulic circuit, a classification system is proposed. The acceptance of this
      proposed definition and classification schema would allow clinicians and basic
      scientists to communicate effectively, to share information and results, and to
      develop testable hypotheses.

PMID- 19410152
TI  - Pediatric seizure and epilepsy classification: why is it important or is it
      important?
AB  - The classification of seizures and epilepsy is a divisive (no pun intended)
      topic. Debate ranges from how to classify seizures and epilepsy to whether a
      classification is needed at all. The classification of seizures and epilepsy in
      the pediatric population, specifically in the neonatal age group, differs from
      similar classifications in the adult population. To date, the most workable
      classification documents are the 1981 Classification of Seizures and the 1989
      Classification of the Epilepsies from the International League Against Epilepsy.
      Subsequently, alternative classifications and schemes have been proposed but not
      universally accepted. Some pediatric-specific classifications, again with
      particular emphasis on classifying seizures and epilepsy in the neonatal
      population, have also been proposed. This review examines these classifications
      and attempts to analyze their pediatric-specific components in terms of
      applicability to the pediatric population and for their utility for pediatric
      physician-scientists and health care providers.

PMID- 19410153
TI  - Low-grade glial tumors: are they all the same?
AB  - The most common diagnosis for supratentorial brain tumors in children is a form
      of low-grade glioma. In addition to being a diagnosis on its own, this term has
      become a general category that encompasses many specific diagnoses. Advances in
      immunohistochemistry and pathology classification schemes have led to the
      recognition of these diverse pathologies. Even though the numbers of any given
      tumor type are small, the question has been raised as to whether different
      pathologies require different treatments. We reviewed the published articles on
      treatment and outcomes for all pathologies included under the heading "low-grade
      glioma" to answer this question. Once intervention is deemed necessary, attempted
      complete surgical resection remains the mainstay of treatment for all diagnoses.
      Surgically accessible recurrences are also best managed with repeat resection.
      Unresectable residuals or recurrences can be treated with adjuvant therapies. The
      only pathologic subgroups that may benefit from more aggressive up-front
      treatment are the grade II astrocytomas. Radiation is reserved for older
      children, and chemotherapy protocols are favored in younger children. Although
      the data from adult radiosurgical studies are promising, data for the pediatric
      population are not yet available. Many small lesions and small residuals remain
      unchanged for many years.

PMID- 19410154
TI  - Headaches in patients with shunts.
AB  - Headache is one of the most common afflictions suffered by humans. Headache in
      patients with a shunt triggers a series of events that includes utilization of
      expensive technologies and often potentially dangerous surgical intervention. The
      purpose of this study was to determine the incidence of headaches in patients
      with shunts and, hopefully, the relationship of those headache disorders to the
      treatment of hydrocephalus. The Hydrocephalus Association maintains a self
      reporting database recorded from individuals treated for hydrocephalus and their
      families. This database was mined to determine the incidence of severe headaches
      requiring treatment and interfering with normal life in patients who have been
      treated for hydrocephalus. There were 1,242 responders between the ages of 19
      months and 45 years of age. Of these, 1,233 answered the question, "Do you or
      your family member suffer from (does your child complain of) frequent or chronic
      headaches?" This subset forms the basis of this study. Three groups were defined
      by age: children (19 months-12 years), adolescents (13 years-19 years), and young
      adults (20 years-45 years). Most respondents were initially treated during
      infancy (before 18 months of age); 84% of children and 69% of both adolescents
      and young adults were treated very early in life. Severe headaches became a more
      frequent problem as the age of the population treated for hydrocephalus
      increased. In terms of frequency and severity of headaches, direct comparisons
      with epidemiologic studies of normal populations are difficult because of the
      limitations of data available in the database. However, it is likely that this
      population has a higher incidence of severe headaches than normal populations.
      The cost of management of headaches in this population is very high, and the
      patients are at risk throughout life. Early treatment decisions have a
      significant effect on later quality of life. Strategies that lead to
      normalization of cerebrospinal fluid dynamics and life without shunt dependency
      are justified if they can be shown to improve later quality of life.

PMID- 19410155
TI  - Chronic daily headaches in children and adolescents.
AB  - Headaches, which are common in children and adolescents, represent a significant
      portion of patient complaints in a child neurology practice. Patients with
      episodic headaches, such as migraines with interval-free periods, and patients
      with chronic daily headaches with very few headache-free days, are often
      evaluated and treated differently from each other. The evolution of the
      classification of chronic daily headache has aided epidemiologic efforts. The
      disorder can be primary or related to other neurologic or systemic conditions.
      Comorbid conditions should be identified, and the contributing variables in the
      child's social, emotional, medical, and educational arenas should be assessed.
      The level of disability in terms of school attendance and function can help
      clinicians determine to what extent and how aggressively to treat these children.
      Rescue medications, such as barbiturates and narcotics, which can cause worsening
      of headaches, should be avoided.

PMID- 19410156
TI  - Treatment of hydrocephalus in adults.
AB  - The following patients with multiple complex diagnoses define the adult
      hydrocephalus population: (1) transition patients (previously treated for
      hydrocephalus as children), (2) adults with previously untreated congenital
      hydrocephalus, (3) adults with acquired hydrocephalus with an identifiable
      etiology, and (4) patients with suspected or proven idiopathic normal pressure
      hydrocephalus. Restricting the outpatient care or hydrocephalus clinic definition
      to a single hydrocephalus patient subpopulation limits our understanding of these
      patients and effectively abandons the remaining adult patients with hydrocephalus
      to a less focused and potentially less effective healthcare arrangement. A
      comprehensive adult hydrocephalus clinic model is described and recommended to
      advance our understanding of this diverse patient population, which will
      ultimately lead to the development and provision of a better standard of patient
      care.

PMID- 19410157
TI  - Cervical spine injuries in children: attention to radiographic differences and
      stability compared to those in the adult patient.
AB  - The relative rarity of pediatric cervical spine injuries can impede rapid
      response and efficient care of this patient population. An understanding of the
      unique anatomical, radiographic, and biomechanical characteristics of the
      pediatric cervical spine is essential to the appropriate care of these
      challenging patients. Patterns of injury, diagnosis, and issues related to
      operative and nonoperative management are discussed with a focus on the
      developing spine. Our aim is to improve the understanding of traumatic cervical
      spine injuries in children for all practitioners involved with their care.

PMID- 19410158
TI  - Introduction: the best of Clinical Cornerstone.

PMID- 19410159
TI  - Asthma management and prevention: current perspectives.
AB  - The continuing evolution of asthma treatment and prevention are reflected in
      updated guidelines from the National Asthma Education and Prevention Program and
      Global Initiative for Asthma as well as other recent publications. The 2007
      Expert Panel Report 3 guidelines designate severity and control, mediated by
      considerations of current impairment and future risk, as the primary concepts in
      assessing and monitoring asthma. Severity should ideally be determined at the
      time of diagnosis, after which control becomes the central focus of asthma
      management. In the area of treatment, inhaled corticosteroids (ICSs) remain first
      line therapy for long-term asthma management in children and adults. For patients
      whose severity of asthma requires more than low-dose ICSs, or whose asthma cannot
      be well controlled on monotherapy with low-dose ICSs, evidence supports the
      efficacy of combination therapy consisting of an ICS plus an inhaled long-acting
      beta(2)-agonist (LABA) or an increase to medium-dose ICSs. For children >5 years
      of age and adults not controlled on low-dose ICSs, the combination of a low-dose
      ICS plus an inhaled LABA is equivalent in terms of outcomes to the use of medium
      dose ICS. For children <5 years of age not controlled on low-dose ICSs,
      increasing the dose of ICSs is preferred to the addition of a LABA to low-dose
      ICS therapy as no studies using combination therapy have been conducted for
      patients in this age group. With regard to asthma prevention, approaches to
      primary prevention (to avoid allergen sensitization) and secondary prevention (to
      avoid disease progression) are still very much in the developmental stage, while
      tertiary prevention (to avoid asthmatic stimuli) has been more successful
      particularly in pediatric patients. Written action plans as part of self
      management processes appear to improve physician-patient communication and
      disease status tracking. Other considerations in successful asthma management
      include patient education and monitoring of adherence to treatment regimens.

PMID- 19410160
TI  - Cardiovascular disease and modifiable cardiometabolic risk factors.
AB  - Cardiovascular disease (CVD) is the leading cause of death in the United States
      and many parts of the world. Potentially modifiable risk factors for CVD include
      tobacco use, physical inactivity, hypertension, elevated low-density lipoprotein
      cholesterol, and a cluster of interrelated metabolic risk factors. Over the last
      several decades, efforts to prevent or treat CVD risk factors have resulted in
      significantly lower rates of CVD-related mortality. However, many patients never
      achieve adequate control of CVD risk factors even when these factors have been
      identified. In addition, the growing prevalence of obesity and type 2 diabetes
      mellitus (DM) threatens to undermine the improvements in CVD that have been
      achieved. In the United States, approximately two thirds of adults are overweight
      or obese, and even modest excess body weight is associated with a significantly
      increased risk of CVD-related mortality. Lifestyle interventions to promote
      weight loss reduce the risk of CVD-related illness but are difficult for patients
      to sustain over long periods of time. The increased incidence of obesity has also
      contributed to significant increases in the prevalence of other important CVD
      risk factors, including hypertension, dyslipidemia, insulin resistance, and type
      2 DM. Pharmacologic therapies are currently available to address individual CVD
      risk factors, and others are being evaluated, including endocannabinoid receptor
      antagonists, inhibitors of peroxisome proliferator-activated receptor subtypes
      alpha and gamma, and several agents that modulate the activity of glucagon-like
      peptide-1. The new agents have the potential to significantly improve several CVD
      risk factors with a single medication and may provide clinicians with several new
      strategies to reduce the long-term risk of CVD.

PMID- 19410161
TI  - Pathophysiology and clinical manifestations of osteoporosis.
AB  - Osteoporosis is a complex skeletal disorder in which compromised bone strength
      increases the risk of fragility fractures. Recent scientific advances in bone
      biology and immunology have greatly expanded our insights into the pathogenesis
      of osteoporosis. For those with osteoporotic fractures, however, the physical and
      psychological effects remain severe. Primary care physicians need to understand
      the basic mechanisms of bone physiology and pathophysiology in order to both
      prevent and treat this devastating disorder.

PMID- 19410162
TI  - Identification and treatment of prediabetes to prevent progression to type 2
      diabetes.
AB  - Overt type 2 diabetes is usually preceded by a condition known as prediabetes,
      which is characterized by impaired fasting glucose (IFG) and impaired glucose
      tolerance (IGT). Both IFG and IGT exhibit elevated glucose levels that are not
      sufficient to be classified as diabetes but that represent the development of
      insulin resistance. Achieving glycemic control in patients with prediabetes
      through lifestyle and pharmacologic interventions can effectively prevent or
      delay the development of diabetes and its associated complications. The first
      step, however, is to identify patients at risk. Although patients can be
      identified with an oral glucose tolerance test (OGTT) or a fasting plasma glucose
      (FPG) screening, a normal FPG does not preclude an elevated OGTT and, therefore,
      the presence of prediabetes. For patients who progress to type 2 diabetes,
      intensive therapy aimed at reducing and maintaining glycosylated hemoglobin (A1C)
      levels < 7% has been shown to reduce the risk of complications. An A1C level > or
      = 7% should signal the need to initiate or change therapy to achieve glycemic
      goals.

PMID- 19410163
TI  - Overcoming patient barriers to initiating insulin therapy in type 2 diabetes
      mellitus.
AB  - Data from clinical trials underscore the fact that loss of beta-cell function and
      insulin hyposecretion are progressive in type 2 diabetes. To achieve adequate
      glycemic control, most patients will eventually require insulin. Addition of
      insulin to sulfonylurea therapy, when maximal sulfonylurea does not adequately
      maintain fasting plasma glucose levels at < 108 mg/dL, has been found to be more
      effective than initiating insulin therapy after oral agents have failed to
      maintain glycemic control. Nonetheless, both patients and providers are reluctant
      to begin insulin therapy. Research has shown that providers often delay
      modification of the diabetes treatment regimen because they believe their
      patients would be concerned about starting insulin therapy. In addition, they are
      concerned about patient nonadherence to nonpharmacologic and pharmacologic
      therapy. There are multiple reasons for patient nonadherence to insulin therapy;
      however, patients must be made to understand, early in the course of the disease,
      the progressive nature of type 2 diabetes and that exogenous insulin is an
      additional therapeutic option to help them achieve and maintain adequate glycemic
      control.

PMID- 19410168
TI  - Plagiarism: an unprofessional and dishonest trend creeping into modern writing of
      research and review papers.

PMID- 19410169
TI  - Fixation of tendo Achilles avulsion fracture.
AB  - Achilles tendon ruptures occur commonly in the midsubstance of the tendon,
      usually 2-6 cm proximal to the insertion to the calcaneus. Ruptures near its
      insertion into the calcaneus are less common and mostly found in hyperpronators
      with a heel spur (Haglund's deformity). Avulsion of the bony insertion of the
      Achilles tendon at the calcaneus is infrequent and is diagnosed by radiography.
      Open reduction and internal fixation is indicated to achieve bone to bone healing
      and restoration of the function and continuity of the triceps surae mechanism.
      Screw fixation is not effective to resist the pull out tension of the triceps
      surae. Moreover, the prominent screw head may cause skin impingement. More secure
      fixation method is necessary in order to allow early functional rehabilitation.
      We describe a technique to fix the avulsed fragment of Achilles tendon insertion
      with 2 suture anchors. This can neutralize the pull of the triceps surae and
      early post-operative rehabilitation programme is allowed.

PMID- 19410170
TI  - The advantages gained by the use of modern materials in the post operative
      casting procedure for foot and ankle surgery.
AB  - BACKGROUND: In June 2006, the post operative plaster immobilisation protocol for
      patients undergoing hindfoot and ankle surgery, at our institution, changed from
      multiple plaster changes to the immediate application of a definitive removable
      and reusable split synthetic cast. This study aims to assess the savings to the
      hospital and patient, following this change in practice. METHODS: A retrospective
      analysis of plaster room records from June 2005 to June 2007 was performed. The
      difference in cost to the hospital of the two different post operative journeys
      was then calculated. RESULTS: Two-hundred and twenty-two patients from 2005 to
      2006 were managed at a total cost of 97,125 euro. From 2006 to 2007, 203 patients
      were managed with the new technique at a total cost of 37,860 euro. The net
      saving to the hospital of this change in practice was 251 euro per patient and
      50,953 euro in total, while 203 patient visits and costs associated therewith
      were also saved. CONCLUSIONS: This study demonstrates how small changes in local
      practice can result in significant financial and temporal savings for hospitals
      and patients.

PMID- 19410171
TI  - The effect of sesamoid position on outcome following scarf osteotomy for hallux
      abducto valgus.
AB  - BACKGROUND: Hallux valgus is a common forefoot condition, with numerous
      operations described to correct the deformity. Debate remains as to the relative
      importance of correcting the position of the sesamoid apparatus. METHODS: Forty
      six cases were reviewed. Preoperative and post-operative X-rays were used to
      measure forefoot width, inter-metatarsal angle (IM), hallux valgus (HV) angle and
      sesamoid position (Reynolds stations). Satisfaction was assessed via
      questionnaire. RESULTS: Significant improvements were seen in all radiological
      parameters. 37/43 patients were satisfied with the result. Comparison between the
      satisfied and non-satisfied group revealed significant differences in the IM
      angle (p<0.05) and HV angle (p<0.05). However, patient satisfaction was not
      associated with post-op sesamoid position or change in sesamoid position
      (p>0.05). CONCLUSIONS: This study showed that scarf osteotomy, can successfully
      correct hallux valgus, with high levels of satisfaction. Satisfaction is
      associated with a greater correction of deformity. Improvement in sesamoid
      position was not associated with patient satisfaction.

PMID- 19410172
TI  - The importance of the length of the first metatarsal and the proximal phalanx of
      hallux in the etiopathogeny of the hallux rigidus.
AB  - The purpose of this study was to determine if the relative length of the first
      metatarsal and the proximal phalanx of the hallux, in respect to the total foot
      length, were associated with the incidence of hallux rigidus. For this
      retrospective study, lateral radiographs from 132 cases with hallux rigidus and a
      control group of 132 normal feet were reviewed. We measured the following
      parameters: the index between the foot length and first metatarsal length, the
      proximal phalanx of the hallux length, and the sum of the first metatarsal length
      and the proximal phalanx of the hallux length. We found a statistically
      significant difference (p: 0.002) between the two groups in the Foot L/1st Mtt L
      index, and no statistical difference in the Foot L/Phalanx L index. We think that
      a greater length of first metatarsal is involved in the etiopathogeny of hallux
      rigidus.

PMID- 19410173
TI  - The prevalence of symptomatic posterior tibialis tendon dysfunction in women over
      the age of 40 in England.
AB  - BACKGROUND: To investigate the prevalence of posterior tibial tendon dysfunction
      (PTTD) in women over the age of 40. METHODS: A validated survey was posted to a
      random sample of 1000 women (over 40 years) from a GP group practice in
      Hertfordshire, England. Survey positive women were telephoned and when indicated,
      a detailed examination was performed. RESULTS: There were 582 usable responses.
      The majority indicated they had minor forefoot or no problems. Telephone contact
      was made with 116 women and of those 79 required examination. The diagnosis of
      symptomatic flatfeet was made in 9 patients, 7 patients had stage I PTTD, 12
      patients had stage II PTTD and 9 patients had an adult acquired flatfoot
      deformity. CONCLUSIONS: This is the first report of the prevalence of stage I and
      II PTTD in women (over 40 years). The prevalence is 3.3% and all patients were
      undiagnosed despite characteristic and prolonged symptoms.

PMID- 19410174
TI  - Symptomatic os trigonum in children.
AB  - BACKGROUND: Symptomatic os trigonum is a rare condition well described in adults
      responsible for chronic ankle pain. To date there is no published case of
      successfully managed symptomatic os trigonum in children. METHODS: We
      retrospectively reviewed 4 paediatric patients (11-17) successfully operated on
      for a symptomatic os trigonum through a postero medial approach. One case was
      bilateral. RESULTS: Pain relief was postoperatively obtained in all cases. All of
      the patients were able to return to physical activities after 3 months. The mean
      follow up was 12 months. CONCLUSION: Symptomatic os trigonum may be responsible
      for chronic ankle pain in children and adolescents as well as in adults. The
      surgical treatment is effective in children.

PMID- 19410175
TI  - The effect of pre-operative counselling on smoking patterns in patients
      undergoing forefoot surgery.
AB  - BACKGROUND: Smoking contributes to higher surgical complication rates. Previous
      studies assessing smoking cessation interventions examined the provision of
      comprehensive packages. The use of surgery as an incentive to complement brief
      advice has not been fully evaluated. METHODS: Smokers were counselled and
      referred to their general practitioners for specific cessation strategies.
      Smoking status was recorded prior to surgery, on admission and in post-operative
      clinics. A telephone survey at a mean of 12 months post-operation ascertained
      long-term behavioural changes. RESULTS: Ninety-seven patients underwent surgery
      with twenty-five recorded as smokers. Sixteen stopped smoking pre-operatively; a
      further four reduced their intake, as a direct consequence of counselling. No
      patients were previously aware of the detrimental effects of smoking associated
      with foot surgery. CONCLUSIONS: Surgery provides an incentive for smoking
      cessation, maintained post-operatively. Although forefoot fusions and arthrodeses
      were used in our study, the results are transferable to other branches of
      orthopaedic surgery.

PMID- 19410176
TI  - Percutaneous fenestration of the anteromedial aspect of the calcaneus for
      resistant heel pain syndrome.
AB  - INTRODUCTION: The failure of conservative treatment of chronic heel pain might
      cause prolonged disability from continued discomfort and pain, which mandates a
      further treatment modality. AIM OF STUDY: The presentation of the results of
      percutaneous fenestration of the anteromedial aspect of the calcaneus for
      symptomatic relief of resistant heel pain syndrome. MATERIAL AND METHODS: Between
      September 2001 and August 2006, 34 patients (38 feet) with chronic heel pain
      syndrome reported an unacceptable level of pain despite intensive conservative
      treatment. There were 23 females and 11 males with an average age of 41 years (25
      59 years). The average follow-up was 46 months (range, 14-84 months). Clinical
      evaluation of the intensity of pain (VAS score system), walking distance,
      standing duration, fascial tenderness, and ankle and subtalar joint motion were
      evaluated preoperatively and at regular follow-up. RESULTS: The preoperative pain
      score level was 8.4 (range, 6-10). The mean postoperative VAS for pain at 4 weeks
      was 5.89 (range, 3-9), at 8 weeks the value was 3.98 (range, 2-7), at 4 months
      2.46 (range, 2-5), at 8 months 1.7 (range, 0-3) and at 12 months zero. A clinical
      improvement was seen in all patients irrespective of the duration of symptoms
      (p=0.0041). Three heels (7.9%) had partial relief of pain, but after 43 weeks had
      complete subsidence of pain. Complications include three transient paraesthesias
      at the distribution of the medial calcaneal nerve that resolved spontaneously
      after 8 weeks post-surgery. CONCLUSION: The results suggest the technique of
      percutaneous fenestration is a significantly effective treatment modality for
      patients with recalcitrant heel pain syndrome after failed conservative
      treatment. The described technique may provide a useful method for treating
      refractory heel spur syndrome without resorting to invasive surgical techniques
      and warrants further study.

PMID- 19410177
TI  - Coeliac disease presenting with bilateral fibular stress fractures.
AB  - We present the case of an apparently healthy 22-year-old female who presented
      with atraumatic stress fractures of both fibulae. Further investigation
      demonstrated that she had osteopoenia secondary to occult coeliac disease. The
      fractures were successfully treated non-operatively. The awareness of the
      prevalence of occult coeliac disease is increasing due to simpler diagnostic
      tests, as is its significance as a cause of secondary osteoporosis. Knowing the
      relationship between these two conditions will help orthopaedic surgeons treating
      such patients to refer them promptly to appropriate specialists.

PMID- 19410178
TI  - Revision of STAR total ankle replacement to hybrid AES-STAR total ankle
      replacement-a report of two cases.
AB  - Revision of a failed total ankle replacement is a surgical challenge due to
      paucity of the revision ankle implants. We report early results of two cases in
      which Scandinavian Total Ankle Replacements (STAR) were revised to hybrid AES
      (Ankle Evolution System)-STAR replacements for aseptic loosening of the tibial
      components. We are not aware of any similar case report in the literature
      reporting hybrid total ankle replacements.

PMID- 19410179
TI  - Osteomyelitis of the calcaneus due to atypical Mycobacterium.
AB  - World wide tuberculous infection of bone remains common but there are few case
      reports of atypical mycobacteria causing bone infection. A case is reported of
      recurrent osteomyelitis of the calcaneus due to such an atypical Mycobacterium
      and associated with interferon-gamma receptor deficiency (IFN-gamma) receptor
      deficiency.

PMID- 19410180
TI  - Treatment of equinocavovarus deformity in a severely hemophilic child: the role
      of a monolateral multiplanar-geared fixation device.
AB  - Equinovarus deformity is associated with various disorders and diseases,
      including this case of recurrent hemarthrosis due to hemophilia. The patient
      demonstrated progressive deformation in the ankle and foot over the course of
      several years of evaluation. Until medical hemostatic control was possible,
      surgery was contraindicated. At age 9, therapeutic control of bleeding was
      attained, and surgical intervention was initiated. Due to concerns for skin and
      soft tissue compromise in this patient, a monolateral multiplanar-geared external
      fixator (M2 MultiPlanar MiniRail, Orthofix) was placed using two sets of half
      pins. The use of the M2 fixation device demonstrated its ease of use and
      application, along with the staged correction that was completed both in the
      orthopaedic office and at home. This case presents an effective approach to the
      surgical correction of equinocavovarus deformity using a monolateral multiplanar
      geared fixation device.

PMID- 19410181
TI  - Epithelioma cuniculatum: A case report.
AB  - Epithelioma cuniculatum (carcinoma cuniculatum) is a rare, low-grade verrucous
      carcinoma of the foot first described in 1954. We present a case report of a 55
      year-old man with an enlarging lesion on the sole of his right foot. Despite
      initial benign pathology the lesion continued to grow, soften in consistency and
      develop a foul odour. Repeat biopsy showed a well-differentiated squamous cell
      carcinoma and below-the-knee amputation was required. Epithelioma cuniculatum
      presents as a slow growing mass on the plantar aspect of the foot. Diagnosis is
      often delayed and may require multiple biopsies. Lesions rarely metastasise but
      more commonly invade locally requiring wide surgical excision.

PMID- 19410182
TI  - Optometry and optics in Europe.

PMID- 19410183
TI  - Dopamine dysregulation syndrome in a patient with restless legs syndrome.
AB  - A middle-aged architect, suffering from familial, idiopathic, levodopa-responsive
      restless legs syndrome (RLS) progressively abused levodopa for 10 years, to the
      point of taking 20 tablets/day (4000 mg/day) for 6 months. Such abuse (possibly
      linked to the rewarding effect of dopamine) has been recently monitored in the
      context of Parkinson's disease (PD) (the "dopamine dysregulation syndrome").
      Physicians who now routinely treat RLS patients with dopaminergic agents should
      be aware of this abuse potential. This case also constitutes an experimental
      model. As levodopa abuse has only been described in patients with PD, it was
      suspected to be promoted by central dopamine depletion (with consequent
      sensitization of dopamine receptors). This idea should be revised because
      functional imaging showed that this RLS patient had no dopamine depletion. Later,
      he had no impulse disorders (no gambling, hypersexuality, excessive shopping),
      which occur with dopamine agonists, suggesting that levodopa abuse and impulse
      disorders can result through different mechanisms.

PMID- 19410184
TI  - Male circumcision: a cancer prevention strategy?

PMID- 19410185
TI  - EGFR testing in lung cancer is ready for prime time.

PMID- 19410186
TI  - A silver lining on the horizon for glioblastoma.

PMID- 19410187
TI  - Could it be that less is more?

PMID- 19410188
TI  - Radical prostatectomy: what have we learned?

PMID- 19410189
TI  - Population-based clinical epidemiology of familial cancer: lessons for
      oncologists.

PMID- 19410190
TI  - Immune reconstitution after HLA mismatched haemopoietic stem-cell
      transplantation.

PMID- 19410191
TI  - Concurrent hormone and radiation therapy in patients with breast cancer: how does
      chemotherapy affect treatment?

PMID- 19410192
TI  - Concurrent hormone and radiation therapy in patients with breast cancer: how does
      chemotherapy affect treatment?

PMID- 19410194
TI  - Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an
      international consensus statement.
AB  - Evidence clearly shows a chemopreventive effect for aspirin and other non
      steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and probably
      other cancer types; however, data on the risk-benefit profile for cancer
      prevention are insufficient and no definitive recommendations can be made.
      Aspirin has emerged as the most likely NSAID for use in chemoprevention because
      of its known cardiovascular benefit and available safety and efficacy data. Other
      traditional NSAIDs, particularly sulindac, and selective COX-2 inhibitors are now
      given to patients at high risk of colorectal cancer, although these drugs do not
      provide cardioprotection. More studies of aspirin and cancer prevention are
      needed to define the lowest effective dose, the age at which to initiate therapy,
      the optimum treatment duration, and the subpopulations for which the benefits of
      chemoprevention outweigh the risks of adverse side-effects. Although it might be
      possible to answer some of these questions with longer follow-up of existing
      clinical trials, randomised controlled trials with new study designs will be
      needed. Future projects should investigate the effects of aspirin treatment on
      multiple organ systems. Cancers of interest are colorectal, breast, prostate,
      lung, stomach, and oesophageal. The main side-effect of aspirin is peptic ulcers;
      therefore coadministration of aspirin with a proton-pump inhibitor is an
      attractive option and is under investigation in the AspECT trial.

PMID- 19410195
TI  - Mechanisms in the pathogenesis of malignant tumours in neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is a familial tumour syndrome. Malignant tumours
      can arise in the nervous and non-nervous system in either childhood or adulthood,
      with malignant peripheral nerve sheath tumours being most common.
      Rhabdomyosarcoma and neuroblastoma are paediatric neoplasms that are more common
      in children with NF1 than in those without the syndrome. Gastrointestinal stromal
      tumours, somatostatinomas, breast cancer, and phaeochromocytomas are seen in
      adults with NF1. Several pathways are thought to be involved in the development
      of tumours associated with NF1: rat sarcoma viral oncogene homologue (RAS)
      mitogen activated protein kinase (MAPK), mammalian target of rapamycin (mTOR),
      and P21 protein (Cdc42/Rac)-activated kinase 1 (PAK1). New insights into the
      pathogenesis of these tumours will lead to a better understanding of tumour
      origin and development and will hopefully allow the discovery of new and specific
      treatments.

PMID- 19410196
TI  - Melanoma of the small intestine.
AB  - Intestinal melanomas can be primary tumours or metastases of cutaneous, ocular,
      or anal melanomas. Primary intestinal melanoma is extremely rare, whereas
      metastatic melanoma of the small bowel is common because of the tendency for
      cutaneous melanoma to metastasise to the gastrointestinal tract. Because
      distinguishing between primary and metastatic intestinal melanoma can be
      difficult, the main features of each are discussed, and the diagnostic images
      used to detect intestinal melanoma are assessed. Routine barium examinations and
      CT have limited sensitivity, but PET imaging can improve detection of melanoma
      metastases to the small bowel. Although various treatment strategies have been
      tried in patients with intestinal melanoma, surgical removal of intestinal
      metastases is the treatment of choice in patients with resectable tumours. No
      systemic therapy improves survival in patients with melanoma metastatic to the
      intestines; thus, the prognosis for these patients is poor. Patients with primary
      melanoma of the small intestine have a worse prognosis than do patients with
      metastases of cutaneous melanoma.

PMID- 19410198
TI  - The bacterium that could cause cancer.

PMID- 19410197
TI  - Should we be surprised at the paucity of response to EGFR inhibitors?
AB  - Data suggest that neither our current understanding of the function and
      signalling of epidermal growth factor receptor (EGFR), nor measurements of
      receptor expression are reliably predictive of therapeutic responses to EGFR
      inhibitors. The time has now come to consider whether such poor correlation
      between receptor expression and clinical response is caused by poor assays or by
      more fundamental issues relating to the in-vivo function of EGFR. Revisiting some
      of the early findings of the biology of EGFR function and understanding the
      limitations of immunohistochemistry as a quantitative technique might provide
      some clues. However, we still have a lot to learn about this receptor, its many
      ligands, and its binding partners in normal physiology and disease.

PMID- 19410199
TI  - Mini-symposium: primary ciliary dyskinesia.

PMID- 19410200
TI  - Primary ciliary dyskinesia: when to suspect the diagnosis and how to confirm it.
AB  - Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive condition. The
      signs and symptoms are due to congenital abnormalities of ciliary structure and
      function, resulting in impaired mucociliary clearance. This affects the ciliated
      epithelium lining the nose, sinuses, Eustachian tube and airways. As a
      consequence, the patient typically presents with a range of features, including
      recurrent upper and lower respiratory tract infections, persistent glue ear and
      possible hearing deficit. Around half of all patients will have situs anomalies,
      most typically situs inversus totalis. The most significant morbidity results
      from the development of bronchiectasis. Access to early diagnosis and effective
      treatment is essential to reduce disease progression and to alleviate the burden
      of symptoms. This review aims to provide a clinical guide to what to look for and
      when to suspect the diagnosis. Recent advances in the screening and diagnostic
      tests available will be outlined, as well as some future directions that aim to
      enhance the current diagnostic techniques.

PMID- 19410201
TI  - Ciliary defects and genetics of primary ciliary dyskinesia.
AB  - Cilia are evolutionarily conserved structures that play key roles in diverse cell
      types. Motile cilia are involved in the most prominent ciliopathy called primary
      ciliary dyskinesia (PCD) that combines respiratory symptoms, male infertility,
      and, in nearly 50% cases, situs inversus. The diagnosis of PCD relies on the
      identification of ciliary abnormalities that mainly concern outer and/or inner
      dynein arms (ODA, IDA). PCD is a genetic condition, usually inherited as an
      autosomal recessive trait. To date, six genes have been clearly implicated in
      PCD. Two "major" genes, DNAI1 and DNAH5, underlie PCD in nearly half of the
      patients with ODA defects, whereas RPGR, DNAH11 and TXNDC3 are implicated in rare
      families with specific phenotypes (retinitis pigmentosa, abnormal beating of
      structurally normal cilia, and situs ambiguous, respectively). The relative
      contribution of DNAI2 is currently being assessed. In all the other patients with
      ODA or other ultrastructural defects, the causative genes remain to be
      identified.

PMID- 19410202
TI  - Management of primary ciliary dyskinesia: the lower airways.
AB  - Primary ciliary dyskinesia (PCD) is a genetic disease associated with defective
      ciliary structure and function. Chronic oto-sino-pulmonary infection is the most
      common clinical presentation. Patients should be monitored in centres with
      expertise in PCD. Regular respiratory monitoring consists of lung function tests,
      adapted to the patient's age, and cough swab or sputum cultures. Chest X-rays are
      insensitive but the use of high-resolution computed tomography should be
      considered carefully to avoid excessive radiation. Treatment of the chronic
      suppuration of the lower airways relies on antibiotics to which the isolated
      bacteria are sensitive, together with respiratory physiotherapy and exercise to
      clear excessive bronchial secretions. Bronchodilators and anti-inflammatory
      agents have no proven benefit and should be prescribed, if at all, on an
      individual basis. Treatment of the lower airways should always be in conjunction
      with that of the upper airways. Importantly in PCD, respiratory disease may be
      controlled with the use of early, adequate and aggressive management.

PMID- 19410203
TI  - Primary ciliary dyskinesia: prospects for new therapies, building on the
      experience in cystic fibrosis.
AB  - Primary ciliary dyskinesia (PCD) is a genetic disease associated with abnormal
      ciliary structure and function, leading to impaired mucociliary clearance, an
      important primary innate defense mechanism that protects the lungs. Drugs that
      can effectively treat PCD should overcome the defect in ciliary function and
      increase the mucociliary clearance. However, there are currently no therapeutic
      strategies that correct the inborn error of ciliary dysfunction to restore
      mucociliary clearance. It is unclear if osmolar agents like hypertonic saline or
      mannitol, therapies that increase the respiratory surface hydration like ion
      channel regulators, or therapies aimed at reducing inflammation or mucus
      production, or softening the mucus will be effective in PCD. Many of these
      modalities are used in cystic fibrosis, yet no evidence exists to support their
      routine use in PCD. Newer genetic modifiers show an exciting potential for
      personalized medication, combining selection of patients with a common genetic
      mutation and a drug treatment that has been specifically designed to overcome
      that mutation, and will greatly enhance the therapeutic arsenal for PCD. This
      review summarizes current and future prospects for these therapeutic options.

PMID- 19410204
TI  - Allergic rhinitis.
AB  - Childhood rhinitis may be classified into non-allergic and allergic. Allergic
      rhinitis is further divided into seasonal and perennial. Seasonal rhinitis is a
      disease particularly of teenagers and young adults and appears to be less common
      in primary and pre school age children. In seasonal rhinitis, with relevant grass
      pollen sensitization, the link between the allergen exposure and rhinitis is
      clear cut. However, in other situations such as perennial rhinitis and house dust
      mite allergen sensitization, the link between symptoms and allergen exposure is
      less certain. Avoidance of allergens often proves to be difficult in practice.
      Intranasal steroids are the treatment of choice for persistent moderate-severe
      allergic rhinitis and are more effective than antihistamines for relief of nasal
      obstruction. Antihistamines are effective for control of histamine related
      symptoms such as itching, rhinorrhoea and sneezing. The use and benefits of
      sublingual or injectable immunotherapy in children are controversial.

PMID- 19410205
TI  - Sublingual immunotherapy for children: Are we there yet? Defining its role in
      clinical practice.
AB  - Immunotherapy in various forms has been used to treat allergic disorders since
      the early 19th century. Subcutaneous immunotherapy is now well established for
      the treatment of insect anaphylaxis and allergic rhinitis. The route of
      administration and possibility of severe adverse reactions to subcutaneous
      immunotherapy make sublingual immunotherapy an appealing alternative, especially
      for the paediatric patient. This form of immunotherapy has been increasingly used
      in Europe, and over the past decade several meta analyses have attempted to
      provide evidence for its efficacy in the treatment of seasonal and perennial
      allergic rhinitis and in asthma, both in the adult and paediatric population.
      Several trials have also shown a potential immunomodulatory effect of sublingual
      immunotherapy, with evidence of a reduction in the progression from allergic
      rhinitis to asthma and reduced new aeroallergen sensitisation. This review will
      give an overview of the current evidence for sublingual immunotherapy in the
      paediatric population.

PMID- 19410206
TI  - Assessment of thoraco-abdominal asynchrony.
AB  - Thoraco-abdominal asynchrony is often observed in many respiratory disorders
      and/or respiratory muscle dysfunctions and clinically assessed as a sign of
      respiratory distress and increased work of breathing. This review describes the
      assessment of thoraco-abdominal asynchrony by respiratory inductance
      plethysmography. Visual inspection of the Konno-Mead plot yields information
      about the relative contribution of the RC and the ABD to respiration and about
      respiratory muscle dysfunction in selected patients. The monitoring of thoraco
      abdominal asynchrony is a useful, non-invasive indicator of respiratory muscle
      load or respiratory muscle dysfunction and can be used to determine response to
      therapy in individual patients. The technique is limited by the fact that it does
      not detect respiratory muscle fatigue and that the occurrence of TAA does not
      always correspond to a clinically relevant respiratory problem, especially in the
      neonatal period.

PMID- 19410207
TI  - Prenatal care for the 21st century: outside the 20th century box.

PMID- 19410208
TI  - Impact of two scheduling systems on early enrollment in a group prenatal care
      program.
AB  - Group care is an effective approach to prenatal care. Yet difficulties in
      recruiting, enrolling, and scheduling women into group care present obstacles to
      optimal program delivery. The purpose of this study was to determine whether the
      use of a scheduling system based on women's estimated date of delivery (EDD)
      decreased gestational age at entry to group care, increased attendance, and
      improved continuity of care. A total of 13 groups were held; seven groups used a
      scheduling system based on appointment availability and six groups used a
      scheduling system based on women's EDD. Compared with the availability-based
      scheduling system, the EDD-based system decreased mean gestational age (23.2 vs.
      21.8 weeks; P = .058) and significantly decreased mean maximum gestational age
      (31.0 vs. 26.3 weeks; P = .002) at entry to group care. The EDD-based system
      increased the mean number of sessions offered per group (6.7 vs. 8.2 sessions; P
      < .001); however, attendance rates were similar across systems. The EDD-based
      system also increased the percentage of women who had the same initial visit and
      group provider (78.0% vs. 85.5%; P = .303). The use of this system by other
      health care facilities could ease the task of enrolling a sufficient number of
      participants into group care, minimize the need for women to change care
      providers if they desire group care, and allow more time for educational
      activities and the development of social networks for women by offering more
      sessions per group.

PMID- 19410209
TI  - "I wasn't alone"--a study of group prenatal care in the military.
AB  - The military has recognized that health and quality of life for service members
      are closely tied to the resources for their families, including how they are
      cared for during pregnancy and childbirth. However, there has been little
      examination of women's experience with different models of prenatal care (PNC) in
      military settings. The purpose of this article is to describe the results of a
      qualitative study of women's experiences with the CenteringPregnancy model of
      group PNC compared to individual PNC in two military health care settings. This
      clinical trial enrolled 322 women who were randomized into group or individual
      PNC at two military treatment facilities. Qualitative interviews were completed
      with 234 women during the postpartum period. Interpretative narrative and
      thematic analysis was used to identify three themes: 1) "I wasn't alone"-the
      experience with group PNC; 2) "I liked it but..."-recommendations to improve
      group PNC; and 3) "They really need to listen"-general concerns across the sample
      about PNC. Greatest concerns of women in individual PNC included lack of
      continuity and time with the provider. Our military families must be assured that
      their health care system meets their needs through personal and family-centered
      care. Group PNC offers the potential for continuity of provider while also
      offering community with other women. In the process, women gain knowledge and
      power as a health care consumer.

PMID- 19410210
TI  - Issues in pregnancy dating: revisiting the evidence.
AB  - As the end point date in pregnancy, the estimated date of delivery provides
      guidance for the timing of specific prenatal tests, gauges fetal growth, and
      informs critical decision making for specific obstetric complications. It is
      prudent to use the most evidenced-based methods available to accurately determine
      gestational age. This article explores the accuracy of both menstrual and
      ultrasound dating techniques and discusses some of the issues and limitations for
      each method. In addition, a simple formula called the rule of eights can be used
      to determine a final estimated date of delivery when a discrepancy between
      menstrual and ultrasound dating occurs.

PMID- 19410211
TI  - Risk assessment and risk distortion: finding the balance.
AB  - Pregnancy and birth have been conceptualized as medically problematic, with all
      pregnant women considered at risk and in need of medical monitoring. Universal
      application of risk scoring and surveillance as preemptive strategies in an
      effort to reduce risk is now standard obstetric practice. Labeling women "high
      risk" can result in more unnecessary interventions and have negative psychologic
      sequelae. When perceived pregnancy risk is out of proportion to the real risk,
      and when risk management procedures are applied to all women with benefit for
      only a few, the use of technology in caring for pregnant women becomes
      normalized. A learned reliance on technology can diminish women's own
      authoritative knowledge of pregnancy and birth. This may also have the unintended
      consequence of contributing to birth fear, a phenomena becoming more widely
      recognized. Health care provider-patient communication about pregnancy risk can
      be presented in a manner that encourages informed compliance rather than informed
      choice. Evidence-based risk assessment is essential to providing optimal prenatal
      care. Using tools such as the Paling Palette can help health care providers
      present balanced and readily understood information about risk.

PMID- 19410212
TI  - Caring for women with abnormal papanicolaou tests during pregnancy.
AB  - The Papanicolaou (Pap) test is one of the best screening tests available for
      cancer detection and has achieved widespread acceptance among women. Pregnancy
      provides a valuable opportunity to educate and screen women for cervical cancer
      when receiving prenatal care. However, evolving knowledge about the course of
      human papillomavirus infection (HPV) in women, new technologies, and the advent
      of vaccines are driving radical changes in practice and new ways to consider
      cervical cancer screening. Modifications in the 2006 Consensus Guidelines for the
      Management of Women with Abnormal Cervical Cancer Screening Tests are most
      evident among adolescents. Because of high rates of HPV regression, pregnant
      adolescents with minor Pap abnormalities may now be followed rather than referred
      for immediate colposcopy. Postponing colposcopy in pregnant, reproductive-age
      women with minor Pap changes until after delivery is now acceptable. Pregnant
      immunocompromised women with abnormal Pap tests are followed similarly to
      pregnant women in the general population. While a strong evidence base is
      gradually emerging to support guideline revisions, the highest quality evidence
      may not yet be available for all recommendations. Midwives can keep abreast of
      the science while using clinical judgment to provide safe and expert cancer
      screening care to women.

PMID- 19410213
TI  - Leg cramps and restless legs syndrome during pregnancy.
AB  - Sleep disturbance during pregnancy can result in excessive daytime sleepiness,
      diminished daytime performance, inability to concentrate, irritability, and the
      potential for an increased length of labor and increased risk of operative birth.
      Sleep disturbance may be the result of a sleep disorder, such as leg cramps, a
      common yet benign disorder, or restless legs syndrome, a sensorimotor disorder.
      Both disrupt sleep, are distressing to the pregnant woman, and mimic one another
      and other serious disorders. During pregnancy, up to 30% of women can be affected
      by leg cramps, and up to 26% can be affected by restless legs syndrome.

PMID- 19410214
TI  - Women's perceptions of access to prenatal care in the United States: a literature
      review.
AB  - Women report many barriers to accessing prenatal care. This article reviews the
      literature from 1990 to the present on women's perceptions of access to prenatal
      care within the United States. Barriers can be classified into societal,
      maternal, and structural dimensions. Women may not be motivated to seek care,
      especially for unintended pregnancies. Societal and maternal reasons cited for
      poor motivation include a fear of medical procedures or disclosing the pregnancy
      to others, depression, and a belief that prenatal care is unnecessary. Structural
      barriers include long wait times, the location and hours of the clinic, language
      and attitude of the clinic staff and provider, the cost of services, and a lack
      of child-friendly facilities. Knowledge of women's views of access can help in
      development of policies to decrease barriers. Structural barriers could be
      reduced through changes in clinic policy and prenatal care format, and the
      creation of child-friendly waiting and examination rooms. Maternal and societal
      barriers can be addressed through community education. A focus in future research
      on facilitators of access can assist in creating open pathways to perinatal care
      for all women.

PMID- 19410216
TI  - Developing guidelines and maintaining quality in antenatal care.
AB  - Clinical practice guidelines are mandated by American College of Nurse-Midwives
      Standards for the Practice of Midwifery. Guidelines should be evidence-based and
      pertinent to the population served. Guidelines assist midwifery practices in the
      evaluation and maintenance of quality care. The development of clinical practice
      guidelines should be rigorous and scientific. There are several sources available
      to midwives to aid in the development of practice guidelines.

PMID- 19410217
TI  - Fetal loss: addressing the evaluation and supporting the emotional needs of
      parents.

PMID- 19410215
TI  - Women's experience of prenatal care: an integrative review.
AB  - The objective of this study was to identify, synthesize, and critically analyze
      published research on women's experiences of prenatal care. A search of online
      databases and relevant citations for research published from 1996 to 2007 was
      conducted. Thirty-six articles were reviewed. Qualitative analysis methods were
      used, assisted by research software. This review found that some women were
      treated respectfully and reported comprehensive, individualized care. However,
      some women experienced long waits and rushed visits, and perceived prenatal care
      as mechanistic or harsh. Women's preferences included reasonable waits, unhurried
      visits, continuity, flexibility, comprehensive care, meeting with other pregnant
      women in groups, developing meaningful relationships with professionals, and
      becoming more active participants in care. Some low-income and minority women
      experienced discrimination or stereotyping and external barriers to care. Further
      research is recommended to understand women's experiences and to develop and
      implement evidence-based, women-centered approaches. Clinicians should inquire
      regarding women's needs and modify care accordingly and also advocate for
      institutional changes that reduce barriers to care. Implementing comprehensive,
      redesigned models of care may be one effective way to simultaneously address a
      variety of women's needs and preferences. If prenatal care becomes more
      attractive and more accessible, women's experience and pregnancy outcomes may
      both improve.

PMID- 19410218
TI  - Informed consent for a vaginal birth after previous cesarean delivery.

PMID- 19410223
TI  - The practice of prelacteal feeding to newborns among Hindu and Muslim families.

PMID- 19410225
TI  - The cost of independence.

PMID- 19410224
TI  - Births attended by certified nurse-midwives in the United States reach an all
      time high: trends from 1989 to 2006.

PMID- 19410226
TI  - An unusual presentation of a lid varix.
AB  - BACKGROUND: A varix usually refers to any abnormally distended vein, artery, or
      lymphatic vessel. Although orbital varices are a common finding, isolated eyelid
      varices are rare. Orbital and lid varices may be associated with additional
      venous malformations elsewhere in the body. The varices can be induced by the
      Valsalva maneuver that leads to increased pressure on the jugular vein. Because
      of the passive nature of the venous system, varices can also be induced by prone
      posture or stooping. Patients with ophthalmic varices may present with proptosis
      or complain of visual disturbance. CASE: A 39-year-old Asian woman presented to
      our clinic for a comprehensive eye examination, with complaints of discomfort
      while lying down, bending, or crying. She experienced a sensation of fullness in
      the right upper eyelid that seemed to have worsened gradually over the prior 9
      years since her last pregnancy. Lid examination found a firm, palpable, nontender
      mass present within the right superior nasal lid after stooping. When filled, the
      induced lid mass could be visualized by ultrasound scan. The mass resolved when
      the patient sat upright. CONCLUSION: Lid varices are rare and usually visually
      benign. Ligation of small sections of the varix, as appropriate, may achieve the
      desired cosmetic effect and improve patient comfort. The varix usually does not
      recur after removal. Venography is used to evaluate the extent and supply of the
      varix before surgery. Cavernous hemangioma, a similar presentation, should be
      differentiated as it carries significant visual morbidity. Careful differential
      diagnosis with magnetic resonance imaging and computed tomography is essential
      with a new-onset or spontaneous varix.

PMID- 19410227
TI  - Risk factors and complications of subconjunctival hemorrhages in patients taking
      warfarin.
AB  - OBJECTIVES: The aim of this study was to identify patients with subconjunctival
      hemorrhage (SCH) on warfarin therapy, to describe risk factors that may
      contribute to SCH development, and to identify complications related to SCH.
      METHODS: A retrospective chart review was conducted including patients treated at
      a university anticoagulation clinic over 2 years (4,334 patient visits). Data
      collection included patient demographics; international normalized ratios (INRs)
      before, at time of, and after SCH; risk factors for increased risk of bleeding;
      patient-reported complications related to SCH; recent changes in medication use;
      and warfarin dosage adjustments made in response to the event. The data were
      summarized using descriptive statistics and frequencies described as percentages.
      RESULTS: Fifteen SCH events were identified at an event rate of 0.35%. Two were
      excluded because of related surgeries near the time of SCH events. The average
      patient age was 67.3 years (range, 51 to 82). A total of 76.9% (n = 10) of
      patients had INRs within the goal range at the appointment before reporting the
      SCH. A total of 46.2% (n = 6) of patients reported alterations in medication
      regimens during the month preceding SCH. Various patient conditions were
      documented that may increase the risk of SCH development. No ophthalmic
      complications were associated with SCHs. CONCLUSIONS: An SCH event rate of 0.35%
      was identified. Many factors may have precipitated SCH; however, ophthalmic
      complications were uncommon.

PMID- 19410229
TI  - Bevacizumab in conjunction with panretinal photocoagulation for neovascular
      glaucoma.
AB  - BACKGROUND: Neovascular glaucoma (NVG) is a type of secondary angle-closure
      glaucoma that can result from severe retinal ischemia, such as proliferative
      diabetic retinopathy. Vascular endothelial growth factor (VEGF) plays a role in
      ocular neovascularization, which can result in NVG. The use of bevacizumab, an
      anti-VEGF antibody, has been shown to lead to the rapid resolution of ocular
      neovascularization and may be used off-label in conjunction with panretinal
      photocoagulation in the treatment of neovascular glaucoma. CASE REPORT: A 71-year
      old man presented with neovascular glaucoma in both eyes secondary to
      proliferative diabetic retinopathy and was treated with both panretinal
      photocoagulation and an intravitreal injection of bevacizumab, which led to the
      rapid resolution of his iris neovascularization. A follow-up examination after 12
      months showed that there was no recurrence of neovascularization. CONCLUSION:
      This case shows the possible beneficial effects of bevacizumab in conjunction
      with panretinal photocoagulation as a treatment option for neovascular glaucoma.

PMID- 19410230
TI  - Polypharmacy and the lack of oculo-visual complaints from those with mental
      illness and dual diagnosis.
AB  - BACKGROUND: Individuals with mental illness (MI) and intellectual disability (ID)
      are characterized as dually diagnosed (DD). These individuals are known to have
      numerous systemic and oculo-visual anomalies. This comorbidity of conditions
      should elicit frequent oculo-visual complaints from these patients during the
      initial review of systems. A search of MedLine yielded one article that was
      published on oculo-visual symptomology/pain associated with MI and DD. This
      report appears to be the first to assess the frequency of these symptoms within
      these 2 unique populations. METHODS: A retrospective analysis of all medical
      records for patients (N = 202) evaluated at the Neumann Association (NA)
      Developmental Disabilities Service of the Illinois Eye Institute was completed.
      Only the records of patients who had either MI or DD and who were prescribed
      antipsychotics, antidepressants, anticonvulsants, or tranquilizers/anxiolytics
      were used for our analysis. Upon record review, 89.9% of MI and 59.4% of DD
      individuals met the above subject criteria. We determined the frequency of ocular
      anomalies, drugs taken, and complaints reported by patients during the initial
      review of systems. RESULTS: The most common documented side effects for the
      targeted drug types were decreased or blurred vision (near or far), visual
      hallucinations, decreased accommodation, and eyelid/conjunctiva irregularities.
      In our sample, the most frequent ocular anomalies encountered were astigmatism
      (50% MI and 37.84% DD), myopia (60.71% MI and 62.16% DD), presbyopia (35.71% MI
      and 37.84%DD), and blepharitis (32.14% MI and 32.43%DD). Additionally, the most
      frequently encountered complaints were no complaints (45.16% MI and 46.84% DD),
      blurry vision (17.74% MI and 17.72% DD), and need new glasses (11.29% MI and
      17.72% DD). CONCLUSIONS: It has been established that MI and DD populations
      exhibit a higher incidence of oculo-visual anomalies (uncorrected refractive
      error, binocular vision anomalies, ocular pathology) than noted in the general
      population. They are also typically taking 1 or more neuropsychotropic
      medications that are frequently associated with undesirable visual side effects.
      Individuals with MI and DD should report numerous complaints associated with the
      medications they take and the oculo-visual anomalies they exhibit during the
      initial case history and the review of systems. The data from this study suggest
      that this is not the case and that only about 50% of those who should have
      complaints actually report them.

PMID- 19410231
TI  - Introduction: veterinary dental radiology.

PMID- 19410228
TI  - Bitemporal visual field defects mimicking chiasmal compression in eyes with
      tilted disc syndrome.
AB  - BACKGROUND: Tilted disc syndrome (TDS) is a congenital optic nerve coloboma
      occurring from embryonic dysgenesis. Several features characterize TDS, including
      an inferiorly located conus, situs inversus of the major retinal vessels, and an
      anomalous disc shape. Commensurate with axonal dysgenesis, visual field defects
      may often occur from TDS, the most common of which involve the temporal and
      superior temporal visual field. These visual field defects can mimic those seen
      in chiasmal compression from a mass lesion. CASES: Five patients from New South
      Wales, Australia, with distinct TDS and bitemporal visual field defects on
      frequency doubling threshold perimetry seemingly respecting the vertical
      hemianopic line are presented. Neuroimaging and medical evaluation of each failed
      to show intracranial chiasmal pathology in any patient. CONCLUSIONS: TDS can
      present with visual field loss resembling that seen in chiasmal disease. Although
      most cases of temporal visual field loss from TDS do not respect the vertical
      hemianopic line and are not true quadrantanopsias, there are instances in which
      this does occur, likely caused by the testing modality used. It is essential that
      patients with suspected intracranial pathology undergo immediate neuroimaging,
      even in the face of TDS.

PMID- 19410232
TI  - Dental radiograph marketing.

PMID- 19410233
TI  - Case based dental radiology.
AB  - Dental radiology is quickly becoming integral to the standard of care in
      veterinary dentistry. This is not only because it is critical for proper patient
      care, but also because client expectations have increased. Furthermore, providing
      dental radiographs as a routine service can create significant practice income.
      This article details numerous conditions that are indications for dental
      radiographs. As you will see, dental radiographs are often critical for proper
      diagnosis and treatment. These conditions should not be viewed as unusual; they
      are present within all of our practices. When you choose not to radiograph these
      teeth, you leave behind painful pathology. Utilizing the knowledge gained from
      dental radiographs will both improve patient care and increase acceptance of
      treatment recommendations. Consequently, this leads to increased numbers of
      dental procedures performed at your practice.

PMID- 19410234
TI  - Dental radiology.
AB  - Dental radiology is the core diagnostic modality of veterinary dentistry. Dental
      radiographs assist in detecting hidden painful pathology, estimating the severity
      of dental conditions, assessing treatment options, providing intraoperative
      guidance, and also serve to monitor success of prior treatments. Unfortunately,
      most professional veterinary training programs provide little or no training in
      veterinary dentistry in general or dental radiology in particular. Although a
      technical learning curve does exist, the techniques required for producing
      diagnostic films are not difficult to master. Regular use of dental x-rays will
      increase the amount of pathology detected, leading to healthier patients and
      happier clients who notice a difference in how their pet feels. This article
      covers equipment and materials needed to produce diagnostic intraoral dental
      films. A simplified guide for positioning will be presented, including a
      positioning "cheat sheet" to be placed next to the dental x-ray machine in the
      operatory. Additionally, digital dental radiograph systems will be described and
      trends for their future discussed.

PMID- 19410235
TI  - Interpretation of dental radiographs.
AB  - Interpretation of dental radiographs is fairly straightforward, with a handful of
      common patterns making up the majority of pathology. This article covers normal
      radiographic anatomy, endodontic disease, periodontal disease, neoplastic
      changes, tooth resorption, caries, and radiographic signs of oral trauma.

PMID- 19410236
TI  - [How to do an adenoidectomy in children?].

PMID- 19410237
TI  - Endothelial nitric oxide synthase gene polymorphisms are not associated with
      recurrent aphthous stomatitis.
AB  - OBJECTIVE: Recurrent aphthous stomatitis (RAS) is a common ulcerative disease of
      the oral mucosa. Recurrent oral aphthous ulceration is the most common and
      consistent feature of the more serious and systemic Behcet's disease (BD).
      Association of endothelial nitric oxide synthase (eNOS) gene polymorphisms with
      BD have been reported in different populations. This study aims to investigate if
      there is an association between these polymorphisms and RAS. METHODS: A case
      control association study using 91 Caucasoid RAS patients and 91 ethnically
      matched systemically healthy controls were genotyped for the -786 and 894 eNOS
      single nucleotide polymorphisms (SNPs) and a variable number of tandem repeat
      (VNTR) polymorphism. Chi-square analysis was used to compare the allele and
      genotype frequencies. RESULTS: No significant difference was found in the
      distribution of allele and genotype frequencies of the -786 and +894
      polymorphisms or the VNTR polymorphism between cases and controls. CONCLUSION:
      eNOS gene polymorphisms associated with BD are not associated with RAS. This
      suggests that the oral ulceration common to both conditions may have a different
      underlying genetic aetiology. Although our data suggests that RAS does not have
      an association with eNOS, it is still possible that nitric oxide is involved in
      the disease process. This could still occur through localised and inflammation
      driven regulation by iNOS.

PMID- 19410238
TI  - Effects of exposure to community violence on school functioning: the mediating
      role of posttraumatic stress symptoms.
AB  - This study investigated the association between exposure to community violence
      (ECV) and school functioning, as well as posttraumatic stress (PTS) symptoms as a
      potential mediator of the relationship. PTS symptoms are commonly associated with
      ECV, and are characterized by difficulty regulating emotions and behaviors. Thus,
      PTS symptomatology may be one mechanism through which community violence impacts
      school functioning. The community-based sample included 47 low-income African
      American children (aged 10-13). Results revealed that ECV was inversely related
      to academic performance and attendance. Symptoms of posttraumatic stress emerged
      as a mediator of the relation between ECV and academic performance. Results have
      implications for urban students who face violence in their communities, and
      emphasize the need for school-based mental health services.

PMID- 19410240
TI  - Comparative solution and solid-phase glycosylations toward a disaccharide
      library.
AB  - A comparative study on solution-phase and solid-phase oligosaccharide synthesis
      was performed. A 16-member library containing all regioisomers of Glc-Glc, Glc
      Gal, Gal-Glc, and Gal-Gal disaccharides was synthesized both in solution and on
      solid phase. The various reaction conditions for different approaches and
      corresponding yields are analyzed and discussed.

PMID- 19410239
TI  - Reaction kinetics and mechanism of acid-catalyzed anomerization of 1-O-acetyl
      2,3,5-tri-O-benzoyl-L-ribofuranose.
AB  - The mechanism of the acid-catalyzed anomerization of 1-O-acetyl-2,3,5-O-benzoyl
      alpha- and -beta-L-ribofuranoses in different acetic acid-acetic anhydride
      mixtures was investigated. The progress of the reactions was followed by NMR
      spectroscopy and the rate constants for the reactions were determined by the use
      of a kinetic model. The site of anomeric activation was clarified by the use of
      (13)C-labeled acetic acid and acetic anhydride, respectively, proving that the
      anomerization takes place by exocyclic C-O cleavage, thus ruling out
      anomerization via acyclic intermediates. The role of the acetyl cation as the
      catalytically active species was further verified.

PMID- 19410241
TI  - Glycosyl iodides. History and recent advances.
AB  - The use of glycosyl iodides as an effective method for the preparation of
      glycosides has had a recent resurgence in carbohydrate chemistry, despite its
      early roots in which these species were believed to be of limited use. Renewed
      interest in these species as glycosylating agents has been spurred by their
      demonstrated utility in the stereoselective preparation of O-glycosides, and
      other glycosylic compounds. This review provides a brief historical account
      followed by an examination of the use of glycosyl iodides in the synthesis of
      oligosaccharides and other glycomimetics, including C-glycosylic compounds,
      glycosyl azides and N-glycosides.

PMID- 19410242
TI  - Chemical structures of water-soluble polysaccharides from Rhizoma Panacis
      Japonici.
AB  - Five polysaccharide samples, coded as RPS1, RPS2, RPS3, RPS4, and RPS5, were
      isolated stepwise from Rhizoma Panacis Japonici (RPJ) by using 0.15M NaCl aqueous
      solution at 25 degrees C, boiling water at 120 degrees C, 0.5M NaOH/0.01M NaBH(4)
      at 10 degrees C, 1.0M NaOH/0.02M NaBH(4) at 10 degrees C, and 19M HCOOH at 4
      degrees C, respectively. The yields were 0.39%, 1.08%, 2.41%, 0.32%, and 0.04%
      for RPS1 to RPS5, respectively. The chemical structures of the polysaccharides
      were highly branched alpha-(1-->4)-D-glucan heteropolysaccharides and the values
      of degree of branch (DB) were in the range of 35-45% for RPS1 to RPS5. All of the
      polysaccharides were water soluble, and their solubility decreased from RPS1 to
      RPS5. The weight average molecular mass were 3.5 x 10(4), 1.47 x 10(5), 1.24 x
      10(6), 9.26 x 10(5), and 1.36 x 10(6) for RPS1 to RPS5, respectively.

PMID- 19410243
TI  - Ex vivo expanded human CD4+CD25+Foxp3+ regulatory T cells prevent lethal
      xenogenic graft versus host disease (GVHD).
AB  - Mouse studies demonstrated that infusion of CD4+CD25+ regulatory T cells (Tregs)
      prevented graft versus host disease (GVHD) lethality after bone marrow
      transplantation (BMT). But the potential impact of human Tregs on GVHD has not
      been well demonstrated. In this study, we demonstrated that human Tregs enriched
      from peripheral blood of healthy donors could be expanded ex vivo to clinically
      relevant cell numbers in 2-3 weeks while maintaining Foxp3, CD25, CTLA-4, and
      CD62L expression as well as in vitro suppressive function. Furthermore, injection
      of human PBL into NOD/SCID mice induced lethal xenogenic GVHD, but co-transfer of
      expanded human Tregs with human PBL significantly enhanced survival, reduced GVHD
      symptoms, and inhibited human IgG/IgM production in the NOD/SCID mice. These
      results demonstrated that ex vivo expanded human Tregs retained their in vivo
      suppressive activity and prevented lethal xenogeneic GVHD, revealing the
      therapeutic potential of expanded human Tregs for GVHD.

PMID- 19410244
TI  - Nakagami Markov random field as texture model for ultrasound RF envelope image.
AB  - The aim of this paper is to propose a new Markov random field (MRF) model for the
      backscattered ultrasonic echo in order to get information about backscatter
      characteristics, such as the scatterer density, amplitude and spacing. The model
      combines the Nakagami distribution that describes the envelope of backscattered
      echo with spatial interaction using MRF. In this paper, the parameters of the
      model and the estimation parameter method are introduced. Computer simulation
      using ultrasound radio-frequency (RF) simulator and experiments on choroidal
      malignant melanoma have been undertaken to test the validity of the model. The
      relationship between the parameters of MRF model and the backscatter
      characteristics has been established. Furthermore, the ability of the model to
      distinguish between normal and abnormal tissue has been proved. All the results
      can show the success of the model.

PMID- 19410245
TI  - Levels of hexachlorobenzene (HCB) in breast milk in relation to birth weight in a
      Norwegian cohort.
AB  - BACKGROUND: Hexachlorobenzene (HCB) is a ubiquitous environmental contaminant
      that, even at low doses, causes destruction of ovarian primordial germ cells in
      experimental studies. However, its potential for reproductive toxicity in humans
      exposed to background levels has not been fully evaluated. Here we examined the
      association between maternal levels of HCB and their infants' birth weight.
      METHODS: HCB was measured in milk samples from a subset of women in the Norwegian
      Human Milk Study (HUMIS), 2003-2006; 300 subjects were randomly chosen from the
      cohort and 26 from all small for gestational age (SGA) children. Additional
      information was obtained through questionnaires and the Medical Birth Registry.
      RESULTS: Overall, HCB was associated with birth weight (adjusted b = -90 g per 8
      microg/kg milk fat, 95% CI-275 to 8) and with SGA (odds ratio 1.8, 95% CI 0.9-3.7
      per 8 microg/kg milk fat (difference between the 10th and the 90th percentile)).
      After stratification, however, the association was present only among smokers.
      For birth weight for past or current smokers: b = -282, CI -467 to -98; for never
      smokers: b = 0.5, CI -149 to 150, p-value for interaction: 0.01. Similar results
      were observed for head circumference, crown-heel length, and SGA. CONCLUSIONS: We
      saw a moderate association between HCB and markers of impaired fetal growth among
      past and current smokers. This finding may be non-causal and due to underlying
      genetic variants tied to both growth and breakdown of HCB or to confounding by
      unmeasured toxicants that coexist in exposure sources. It may, however, also
      result from HCB exposure.

PMID- 19410247
TI  - Predictive value of embryo grading for embryos with known outcomes.
AB  - OBJECTIVE: To compare pronuclear morphology (Z-score), day 3 embryo grade, and
      day 3 cell number in the prediction of successful implantation rates (IRs),
      including cycles in which all or none of the embryos implanted. DESIGN:
      Retrospective analysis. SETTING: University-based IVF center. PATIENT(S): Four
      hundred twenty-six fresh IVF day 3 transfers of 852 embryos in women <36 years of
      age from January 2000 to December 2003 in whom all or none of the embryos
      implanted. MAIN OUTCOME MEASURE(S): Evaluation of Z-scores, embryo morphology,
      cell number, and IR. RESULT(S): Day 3 parameters were more predictive than Z
      scores. When early parameters were poor (Z-score) but late parameters were both
      good, the IR was 38%, compared with 4% when the Z-score was good but the late
      parameters were poor. CONCLUSION(S): Embryo grading systems are useful in the
      prediction of embryo implantation. In particular, cell number and embryo grade
      are more predictive than Z-scores. Therefore, late parameters have a better
      prognostic value than Z-scores when selecting embryos for transfer.

PMID- 19410246
TI  - Laparoscopic treatment of interstitial twin pregnancy.
AB  - OBJECTIVE: To describe a conservative management by laparoscopy of an unusual
      interstitial twin pregnancy. DESIGN: Case report. SETTING: University hospital.
      PATIENT(S): A 27-year-old woman, pregnant at 6th week of amenorrhea with
      interstitial twin pregnancy. INTERVENTION(S): The woman was submitted to two- and
      three-dimensional transvaginal ultrasound and to diagnostic hysteroscopy.
      Subsequently, we performed a laparoscopic procedure: conical exeresis of the
      uterine cornu using a monopolar hook without involving the uterine cavity. MAIN
      OUTCOME MEASURE(S): Conservation of the uterus, fertility preservation.
      RESULT(S): Successful conservative treatment of interstitial twin pregnancy.
      CONCLUSION(S): Conservative laparoscopic surgery can be used successfully in
      hemodynamically stable patients with an interstitial pregnancy.

PMID- 19410248
TI  - Sibling and self ovum donation for sisters with an intermediate FMR1 mutation:
      what's a program to do?
AB  - OBJECTIVE: To increase awareness of the unique clinical and ethical
      considerations invoked by the request of a patient with premature ovarian failure
      (POF) and her nulliparous sister, both with intermediate-size mutations in
      fragile X mental retardation 1 (FMR1), to pursue sibling ovum donation. DESIGN:
      Case report. SETTING: Academic medical center. PATIENT(S): A 32-year-old woman
      with POF and her 26-year-old sister with occult diminished ovarian reserve, both
      of whom are carriers of an intermediate-size mutation in FMR1. INTERVENTION(S):
      Prospective donor ovarian function testing, genetic testing and consultation, and
      psychological evaluation; institutional assisted reproduction ethics committee
      consultation, and controlled ovarian hyperstimulation-IVF with cryopreservation
      of embryos for potential future self-use. MAIN OUTCOME MEASURE(S): Successful
      cryopreservation of embryos for autologous use by the prospective donor (younger
      sister) before ovum donation. RESULTS(S): Three blastocysts were frozen.
      CONCLUSION(S): Requests for sibling ovum donation, while understandable and
      ethically sanctioned under typical circumstances, prove particularly challenging
      in some patients with POF given uncertainties regarding the prognosis of the
      currently asymptomatic sister, risks of genetic transmission of POF, and
      fiduciary responsibilities to address the reproductive interests of the
      prospective donor. A multidisciplinary approach was highly beneficial in this
      case.

PMID- 19410249
TI  - Negligible serum anti-mullerian hormone: pregnancy and birth after a 1-month
      course of an oral contraceptive, ovarian hyperstimulation, and intracytoplasmic
      sperm injection.
AB  - OBJECTIVE: To describe a patient with isolated negligible (<0.5 ng/mL or <3.6
      pmol/L) anti-mullerian hormone (AMH) levels who underwent intracytoplasmic sperm
      injection (ICSI) for severe oligoasthenoteratozoospermia, displayed ovarian
      hyperstimulation after a 1-month course of an oral contraceptive (OC), had a
      singleton pregnancy and delivered a healthy boy. DESIGN: Case report. SETTING:
      Reproductive center at a private hospital. PATIENT(S): A 34-year-old woman with
      isolated negligible (<0.5 ng/mL or <3.6 pmol/L) AMH level and poor response to
      controlled ovarian hyperstimulation (COH) and her 38-year-old partner with severe
      oligoasthenoteratozoospermia. INTERVENTION(S): A 1-month course of an OC,
      modified minimal stimulation cycle with recombinant FSH, antagonist (cetrorelix)
      administration to inhibit LH surge, triggered ovulation using 10,000 U of hCG and
      ICSI. MAIN OUTCOME MEASURE(S): Level of AMH, pregnancy, and birth. RESULT(S):
      Three high quality embryos were obtained and transferred 48 hours after ICSI.
      Transvaginal ultrasound at 8 weeks' gestation showed a vital singleton pregnancy.
      The pregnancy continued uncomplicated. The patient gave birth to a healthy boy,
      weighing 3,280 g, by caesarean section at 39 weeks' gestation. CONCLUSION(S):
      Ovarian hyperstimulation, pregnancy, and birth may occur after a short course of
      an OC and ICSI in poor responder, normogonadotropic, regularly menstruating young
      women with isolated negligible AMH.

PMID- 19410250
TI  - Oral infection-inflammatory pathway, periodontitis, is a risk factor for
      endothelial dysfunction in patients with coronary artery disease.
AB  - OBJECTIVE: Several studies have shown that periodontitis is a risk factor for
      cardiovascular diseases. There is an association between inflammation and
      endothelial dysfunction. The purpose of this study was to evaluate endothelial
      function in patients with coronary artery disease (CAD) who had periodontitis.
      METHODS AND RESULTS: We evaluated forearm blood flow (FBF) responses to
      acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium
      nitroprusside (SNP), an endothelium-independent vasodilator, in 101 CAD patients
      with periodontitis (37 men and 11 women, 63+/-12 yr) and without periodontitis
      (36 men and 17 women, 62+/-13 yr). FBF was measured by using strain-gauge
      plethysmography. Circulating levels of C-reactive protein and interleukin-6 were
      significantly higher in the periodontitis group than in the non-periodontitis
      group. FBF response to ACh was significantly smaller in the periodontitis group
      than in the non-periodontitis group. SNP-stimulated vasodilation was similar in
      the two groups. Periodontal therapy reduced serum concentrations of C-reactive
      protein from 2.7+/-1.9 to 1.8+/-0.9mg/L (P<0.05) and interleukin-6 from 2.6+/-3.4
      to 1.6+/-2.6ng/L (P<0.05) and augmented ACh-induced vasodilation from 14.7+/-5.2
      to 20.1+/-6.1mL/(min100mL) tissue (P<0.05) in patients with periodontitis. The
      SNP-stimulated vasodilation was similar before and after treatment. After
      administration of N(G)-monomethyl-l-arginine, a nitric oxide synthase inhibitor,
      FBF response to ACh was similar before and after treatment. CONCLUSION: These
      findings suggest that periodontitis is associated with endothelial dysfunction in
      patients with CAD through a decrease in nitric oxide bioavailability. Systemic
      inflammation may be, at least in part, a cause and predictor of progression of
      endothelial dysfunction.